PMID- 27248359 TI - Neutrophils' sexiness is independent of trendy fashion. PMID- 27248360 TI - Expanding Boundaries: N2 Cleavage and Functionalization beyond Early Transition Metals. AB - Early transition metals are well known to catalyze the cleavage and functionalization of N2 . In this Highlight, recent work showing that a rhenium catalyst is also capable of carrying out this difficult task is summarized, and a synthetic cycle for the stoichiometric incorporation of atmospheric N2 into acetonitrile is presented. PMID- 27248361 TI - Observation of coherent delocalized phonon-like modes in DNA under physiological conditions. AB - Underdamped terahertz-frequency delocalized phonon-like modes have long been suggested to play a role in the biological function of DNA. Such phonon modes involve the collective motion of many atoms and are prerequisite to understanding the molecular nature of macroscopic conformational changes and related biochemical phenomena. Initial predictions were based on simple theoretical models of DNA. However, such models do not take into account strong interactions with the surrounding water, which is likely to cause phonon modes to be heavily damped and localized. Here we apply state-of-the-art femtosecond optical Kerr effect spectroscopy, which is currently the only technique capable of taking low frequency (GHz to THz) vibrational spectra in solution. We are able to demonstrate that phonon modes involving the hydrogen bond network between the strands exist in DNA at physiologically relevant conditions. In addition, the dynamics of the solvating water molecules is slowed down by about a factor of 20 compared with the bulk. PMID- 27248363 TI - RECENT AND NEEDED ADVANCES IN THE UNDERSTANDING, PREDICTION, AND PREVENTION OF SUICIDAL BEHAVIOR. PMID- 27248362 TI - Clusterin levels are increased in Alzheimer's disease and influence the regional distribution of Abeta. AB - Clusterin, also known as apoJ, is a lipoprotein abundantly expressed within the CNS. It regulates Abeta fibril formation and toxicity and facilitates amyloid beta (Abeta) transport across the blood-brain barrier. Genome-wide association studies have shown variations in the clusterin gene (CLU) to influence the risk of developing sporadic Alzheimer's disease (AD). To explore whether clusterin modulates the regional deposition of Abeta, we measured levels of soluble (NP40 extracted) and insoluble (guanidine-HCl-extracted) clusterin, Abeta40 and Abeta42 by sandwich ELISA in brain regions with a predilection for amyloid pathology-mid frontal cortex (MF), cingulate cortex (CC), parahippocampal cortex (PH), and regions with little or no pathology-thalamus (TH) and white matter (WM). Clusterin level was highest in regions with plaque pathology (MF, CC, PH and PC), approximately mirroring the regional distribution of Abeta. It was significantly higher in AD than controls, and correlated positively with Abeta42 and insoluble Abeta40. Soluble clusterin level rose significantly with severity of cerebral amyloid angiopathy, and in MF and PC regions was highest in APOE E4 homozygotes. In the TH and WM (areas with little amyloid pathology) clusterin was unaltered in AD and did not correlate with Abeta level. There was a significant positive correlation between the concentration of clusterin and the regional levels of insoluble Abeta42; however, the molar ratio of clusterin : Abeta42 declined with insoluble Abeta42 level in a region-dependent manner, being lowest in regions with predilection for Abeta plaque pathology. Under physiological conditions, clusterin reduces aggregation and promotes clearance of Abeta. Our findings indicate that in AD, clusterin increases, particularly in regions with most abundant Abeta, but because the increase does not match the rising level of Abeta42, the molar ratio of clusterin : Abeta42 in those regions falls, probably contributing to Abeta deposition within the tissue. PMID- 27248364 TI - Candidate gene approach identifies six SNPs in tenascin-C (TNC) associated with degenerative rotator cuff tears. AB - Evidence for a heritable predisposition to rotator cuff tears (RCTs) is growing. Unrelated Caucasian individuals with surgically diagnosed full thickness RCTs (cases) and elderly Caucasian controls with intact rotator cuffs were screened for differences at the candidate genes: TNC, Col5A1, TIMP-1, MMP-1, MMP-2, MMP-3, MMP-9, and MMP-13. A first cohort (59 cases; 32 controls) was genotyped with the Sequenom MassARRAY iPLEX system. Of 142 SNPs within about 67-kbp of the TNC gene, 30 were tested for differences in proportions between cases and controls. A second, matched cohort (96 patients; 44 controls) was also genotyped for the same 30 SNPs, but with the KASPTM genotyping technology. Combining the two cohorts and after Bonferroni correction, six SNPs were significantly associated with RCT. Compared to controls, RCT patients showed a significantly higher rate of homozygosity at rs72758637, rs7021589, and rs1138545; a significantly higher rate of heterozygosity at rs10759753, rs3789870, and rs7035322 and a higher minor allele frequency at rs3789870. Rs1138545, a missense SNP in exon10 might be of biological significance because it varies the amino acid sequence close to the TNC-FNIII5 domain. The FNIII5 domain binds multiple growth factors and co-ligates with integrins during tendon healing. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:894-901, 2017. PMID- 27248365 TI - Predicting High-Power Performance in Professional Cyclists. AB - PURPOSE: To assess if short-duration (5 to ~300 s) high-power performance can accurately be predicted using the anaerobic power reserve (APR) model in professional cyclists. METHODS: Data from 4 professional cyclists from a World Tour cycling team were used. Using the maximal aerobic power, sprint peak power output, and an exponential constant describing the decrement in power over time, a power-duration relationship was established for each participant. To test the predictive accuracy of the model, several all-out field trials of different durations were performed by each cyclist. The power output achieved during the all-out trials was compared with the predicted power output by the APR model. RESULTS: The power output predicted by the model showed very large to nearly perfect correlations to the actual power output obtained during the all-out trials for each cyclist (r = .88 +/- .21, .92 +/- .17, .95 +/- .13, and .97 +/- .09). Power output during the all-out trials remained within an average of 6.6% (53 W) of the predicted power output by the model. CONCLUSIONS: This preliminary pilot study presents 4 case studies on the applicability of the APR model in professional cyclists using a field-based approach. The decrement in all-out performance during high-intensity exercise seems to conform to a general relationship with a single exponential-decay model describing the decrement in power vs increasing duration. These results are in line with previous studies using the APR model to predict performance during brief all-out trials. Future research should evaluate the APR model with a larger sample size of elite cyclists. PMID- 27248366 TI - Corrigendum. PMID- 27248367 TI - Self-Assembly of Hierarchical Chiral Nanostructures Based on Metal-Benzimidazole Interactions: Chiral Nanofibers, Nanotubes, and Microtubular Flowers. AB - Controlled hierarchical self-assembly of synthetic molecules into chiral nanoarchitectures to mimic those biological chiral structures is of great importance. Here, a low-molecular-weight organogelator containing a benzimidazole moiety conjugated with an amphiphilic l-glutamic amide has been designed and its self-assembly into various hierarchical chiral nanostructures is investigated. Upon gel formation in organic solvents, 1D chiral nanostructure such as nanofiber and nanotube are obtained depending on the solvents. In the presence of transition and rare earth metal ions, hierarchical chiral nanostructures are formed. Specifically, the addition of TbCl3 , EuCl3 , and AgNO3 leads to nanofiber structures, while the addition of Cu(NO3 )2 , Tb(NO3 )3 , or Eu(NO3 )3 provides the microflower structures and microtubular flower structures, respectively. While Eu(III) and Tb(III)-containing microtubular flowers keep the chirality, the Cu(II)-coordinated microflowers lose chirality. More interestingly, the nanofibers formed by the gelator coordinated with Eu(III) or Tb(III) ions show not only the supramolecular chirality but also the circularly polarized luminescence. PMID- 27248368 TI - Shaping nanoscale magnetic domain memory in exchange-coupled ferromagnets by field cooling. AB - The advance of magnetic nanotechnologies relies on detailed understanding of nanoscale magnetic mechanisms in materials. Magnetic domain memory (MDM), that is, the tendency for magnetic domains to repeat the same pattern during field cycling, is important for magnetic recording technologies. Here we demonstrate MDM in [Co/Pd]/IrMn films, using coherent X-ray scattering. Under illumination, the magnetic domains in [Co/Pd] produce a speckle pattern, a unique fingerprint of their nanoscale configuration. We measure MDM by cross-correlating speckle patterns throughout magnetization processes. When cooled below its blocking temperature, the film exhibits up to 100% MDM, induced by exchange-coupling with the underlying IrMn layer. The degree of MDM drastically depends on cooling conditions. If the film is cooled under moderate fields, MDM is high throughout the entire magnetization loop. If the film is cooled under nearly saturating field, MDM vanishes, except at nucleation and saturation. Our findings show how to fully control the occurrence of MDM by field cooling. PMID- 27248369 TI - New Selective Synthesis of Dithiaboroles as a Viable Pathway to Functionalized Benzenedithiolenes and Their Complexes. AB - A synthetic protocol to synthesize 2-bromobenzo-1,3,2-dithiaboroles in one step from easily accessible benzene bis(isopropyl thioether)s has been developed. The reaction is remarkably specific in converting substrates with two adjacent (i)PrS moieties while leaving isolated thioether functions and other functional groups intact. On the basis of the spectroscopic detection or isolation of reaction intermediates, a mechanistic explanation involving a neighbor-group-assisted dealkylation as a key step is proposed. The resulting products featuring one or two dithiaborole units were isolated in good yields and fully characterized. Subsequent methanolysis, which was carried out either as a separate reaction step or in the manner of a one-pot reaction, gave rise to functionally substituted benzenedithiols. The feasibility of a methylphosphoryl-substituted benzenedithiol to act as a dianionic S,S-chelating ligand was demonstrated with the formation of paramagnetic Ni(III) and Co(III) complexes. Selective reduction of the phosphoryl group afforded a rare example of a phosphino dithiol which was shown to act as a monoanionic P,S-bidentate ligand toward Pd(II). All complexes were characterized by spectral data and X-ray diffraction studies, and the paramagnetic ones also by superconducting quantum interference device magnetometry. PMID- 27248370 TI - Energy Decomposition Analysis Based on Absolutely Localized Molecular Orbitals for Large-Scale Density Functional Theory Calculations in Drug Design. AB - We report the development and implementation of an energy decomposition analysis (EDA) scheme in the ONETEP linear-scaling electronic structure package. Our approach is hybrid as it combines the localized molecular orbital EDA (Su, P.; Li, H. J. Chem. Phys., 2009, 131, 014102) and the absolutely localized molecular orbital EDA (Khaliullin, R. Z.; et al. J. Phys. Chem. A, 2007, 111, 8753-8765) to partition the intermolecular interaction energy into chemically distinct components (electrostatic, exchange, correlation, Pauli repulsion, polarization, and charge transfer). Limitations shared in EDA approaches such as the issue of basis set dependence in polarization and charge transfer are discussed, and a remedy to this problem is proposed that exploits the strictly localized property of the ONETEP orbitals. Our method is validated on a range of complexes with interactions relevant to drug design. We demonstrate the capabilities for large scale calculations with our approach on complexes of thrombin with an inhibitor comprised of up to 4975 atoms. Given the capability of ONETEP for large-scale calculations, such as on entire proteins, we expect that our EDA scheme can be applied in a large range of biomolecular problems, especially in the context of drug design. PMID- 27248371 TI - Bioabsorbable zinc ion induced biphasic cellular responses in vascular smooth muscle cells. AB - Bioabsorbable metal zinc (Zn) is a promising new generation of implantable scaffold for cardiovascular and orthopedic applications. In cardiovascular stent applications, zinc ion (Zn(2+)) will be gradually released into the surrounding vascular tissues from such Zn-containing scaffolds after implantation. However, the interactions between vascular cells and Zn(2+) are still largely unknown. We explored the short-term effects of extracellular Zn(2+) on human smooth muscle cells (SMCs) up to 24 h, and an interesting biphasic effect of Zn(2+) was observed. Lower concentrations (<80 MUM) of Zn(2+) had no adverse effects on cell viability but promoted cell adhesion, cell spreading, cell proliferation, cell migration, and enhanced the expression of F-actin and vinculin. Cells treated with such lower concentrations of Zn(2+) displayed an elongated shape compared to controls without any treatment. In contrast, cells treated with higher Zn(2+) concentrations (80-120 MUM) had opposite cellular responses and behaviors. Gene expression profiles revealed that the most affected functional genes were related to angiogenesis, inflammation, cell adhesion, vessel tone, and platelet aggregation. Results indicated that Zn has interesting concentration-dependent biphasic effects on SMCs with low concentrations being beneficial to cellular functions. PMID- 27248372 TI - Assessment of Vascular Disease Prevention Practices in Urban Women. AB - BACKGROUND: Women suffer higher rates of death due to stroke compared to men. In addition, previous studies suggest that women are treated less aggressively for vascular risk factors compared to men. We assessed the quality of primary and secondary vascular prevention at multiple primary care sites within a single region. METHODS: Women more than age of 40 years were eligible for the study. Data from the electronic medical record at multiple primary care locations (internal medicine, family medicine, and geriatrics) were analyzed to assess quality of vascular preventative care. Specific attention was devoted to use of antithrombotic agents, statins, and estrogen. RESULTS: 1,815 women with a mean age of 61 years were reviewed. Seventy-five percent were African American. Patients in the urban practices had higher rates of vascular risk factors and existing vascular disease (heart disease or stroke) compared to the suburban locations. Seventy-one percent of patients with diabetes were receiving statins. For patients with previous stroke/transient ischemic attack (TIA), the use of antiplatelet agents or statins was <70%. Patients >70 years were more likely to receive antiplatelet agents (51% vs. 30%, p < 0.0001) and statins (p < 0.001). CONCLUSIONS: Urban women have higher rates of vascular risk factors and overt vascular disease compared to suburban women. The use of proven secondary prevention medications for patients with prior stroke/TIA was suboptimal. Both primary and secondary prevention should be intensified for urban women. PMID- 27248373 TI - Effect of the 4-h target on time-to-analgesia in an Australian emergency department: a pilot retrospective observational study. AB - Objectives The aim of the present study was to assess the relationship between and the effect of the 4-h target or National Emergency Access Target (NEAT) on the time-to-analgesia (TTA), as well as the provision of analgesia in an adult emergency department (ED). Methods The present study was a pilot descriptive explorative retrospective cohort study conducted in a public metropolitan ED. Eligible presentations for analysis were adults presenting with a documented pain score of >=4 out of 10 between 1 and 14 September 2014. Triage Category 1, pregnant, chest pain and major trauma cases were excluded from the study. As a result, data for 260 patients were analysed. Results Of 260 patients, 176 had analgesia with a median TTA of 49min. Increased NEAT compliance did not significantly decrease TTA. However, when the factors that affected the provision of analgesia were analysed, an association was demonstrated between Admitted and Short Stay NEAT performance and the provision of analgesia. The likelihood of receiving analgesia at all increased as Admitted and Short Stay NEAT compliance improved. Conclusion NEAT is a significant health policy initiative with little clinical evidence supporting its implementation. However, as the Admitted NEAT compliance increases, the probability of receiving analgesia increases, demonstrating a possible link between hospital function and clinical care provision that needs to be explored further. What is known about the topic? The 4 h target or NEAT is a widely used initiative in EDs to allay crowding and access block. However, little is known of its impact on clinical endpoints, such as TTA. What does this paper add? TTA was not significantly reduced as NEAT compliance increased. However, when the focus was on the probability of receiving analgesia, the results demonstrated that an improvement in Admitted and Short Stay NEAT compliance was associated with an increase in the likelihood of patients receiving analgesia. What are the implications for practitioners? NEAT is a relatively recent initiative, hence evidence of its effect on clinically orientated outcomes is limited. Nevertheless, evidence of safety and effectiveness is emerging. The results of the present pilot study provide preliminary data on the timeliness of patient-centred care as demonstrated by TTA and administration of analgesia when required. Further, the results would seem to suggest that the provision of analgesia is affected by how timely patients are moved out of the ED to the in-patient setting. As for future investigations on TTA as a result of NEAT, a wider time period should be considered so that the accurate effect of compliance thresholds (e.g. >=90%, 81-89%, <=80%) of NEAT can be explored. PMID- 27248425 TI - Hierarchic Interaction of Factors Associated With Liver Decompensation After Resection for Hepatocellular Carcinoma. AB - IMPORTANCE: Liver resection is the treatment of choice for hepatocellular carcinoma (HCC) in well-compensated liver cirrhosis. Postoperative liver decompensation (LD) is the most representative and least predictable cause of morbidity and mortality. OBJECTIVES: To determine the hierarchy and interaction of factors associated with the risk for LD and to define applicable risk classes among surgical candidates. DESIGN, SETTING, AND PARTICIPANTS: This retrospective review collected data from 543 patients with chronic liver disease who underwent hepatic resection for HCC from January 1, 2000, through December 31, 2013, in a tertiary comprehensive cancer center. Final follow-up was completed on January 31, 2015, and data were assessed from February 1 to 28, 2015. MAJOR OUTCOMES AND MEASURES: Preoperative prognostic factors and risk stratification for postoperative LD. Multivariate logistic regression was performed, and the independent risk factors for LD were included in a recursive partitioning analysis model. Results were validated by means of 10-fold cross-validation. RESULTS: The analysis included 543 patients, of whom 411 (75.7%) were male, 132 (24.3%) were female, and the median age was 68 (interquartile range, 62-73) years. An independent association with LD was found for major hepatectomy (odds ratio [OR], 2.41; 95% CI, 1.17-4.30; P = .01), portal hypertension (OR, 2.20; 95% CI, 1.13-4.30; P = .01), and Model for End-Stage Liver Disease (MELD) score greater than 9 (OR, 2.26; 95% CI, 1.10-4.58; P = .02). Recursive partitioning analysis confirmed portal hypertension as the most important factor (OR, 2.99; 95% CI, 1.93-4.62; P < .001), followed by extension of hepatectomy with (OR, 2.76; 95% CI, 1.85-4.77; P = .03) and without (OR, 2.98; 95% CI, 1.97-4.52; P < .001) portal hypertension, and MELD score (OR, 1.79; 95% CI, 1.23-2.13; P < .001). Low-risk patients (LD rate, 4.9% [11 of 226]) without portal hypertension underwent minor resection with a MELD score of 9 or less; intermediate-risk patients (LD rate, 28.6% [85 of 297]) had no portal hypertension and underwent major resections or, in case of minor resections, had portal hypertension or a MELD score greater than 9; and high-risk patients (LD rate, 60.0% [12 of 20]) underwent major resection with portal hypertension. Risk-class progression paralleled median length of stay (7, 8, and 11 days, respectively; P < .001) and liver-related mortality (4.4% [10 of 226], 9.0% [27 of 297], and 25.0% [5 of 20], respectively; P = .001). A 10-fold cross-validation of the model resulted in a C index of 0.78 (95% CI, 0.74-0.82) and an overall error rate of 0.06. CONCLUSIONS AND RELEVANCE: The risk for postoperative LD after resection for HCC in chronic liver disease is associated with preoperative hierarchic interaction of portal hypertension, planned extension of hepatectomy, and the MELD score. PMID- 27248426 TI - Considerations of pharmacogenetic testing in children. PMID- 27248428 TI - Patient Preference in Dermatologist Attire in the Medical, Surgical, and Wound Care Settings. AB - IMPORTANCE: Patients' perceptions of their physician can affect subjective and objective outcomes. Physician attire influences patients' perceptions of their physician and consequently may affect patient outcomes. OBJECTIVE: To determine patient preferences for different types of dermatologist attire in dermatology medical, surgical, and wound care clinics. We hypothesized that patients in the dermatology medical setting would prefer professional attire, while patients in the dermatology surgical and wound care setting would prefer surgical scrubs. DESIGN, SETTING, AND PARTICIPANTS: This study analyzed responses to a cross sectional, anonymous survey by English-speaking dermatology patients (aged 18 years or older) at general, surgical, and wound care clinics in an academic center in Miami, Florida. Patients who could not read and understand the survey were excluded. Participants received pictures of a physician wearing business attire, professional attire, surgical attire, and casual attire, and responded by indicating which physician they preferred for each of 19 questions. Frequencies of responses were recorded, and chi2 and regression tests were performed. MAIN OUTCOMES AND MEASURES: Response frequencies. RESULTS: Surveys were administered to 261 persons, and 255 participated and completed enough of the questions to be included in the outcome analyses (118 men, 121 women, 22 unknown [did not answer sex question]), mean (SD) age, 56.3 (18.6) years; about 49% of those who reported their sex were men; 56% were Hispanic; and 85% were white. Approximately 72% of respondents held a college degree or higher. About 63%, 24%, and 13% of respondents were medical, surgical, and wound care dermatology patients, respectively. Roughly 73%, 19%, 6%, and 2% of cumulative responses were for professional, surgical, business, and casual attire, respectively. Respondents who received a picture of a black male or black female physician were more likely to exclusively prefer professional attire: unadjusted odds ratios (ORs) 3.21 (95% CI, 1.39-7.42) and 2.78 (95% CI, 1.18-6.51), respectively, compared with respondents who received a picture of a white male physician. Nonwhite and unemployed respondents were less likely to prefer professional attire exclusively: ORs, 0.28 (95% CI, 0.1-0.83) and 0.28 (95% CI, 0.08-0.99), respectively. Respondents preferred professional attire in all clinic settings, though respondents in the dermatology surgery clinic were less likely to prefer professional attire compared with respondents in the medical dermatology clinic: race-adjusted OR, 0.74 (95% CI, 0.56-0.98). Wound care and medical dermatology respondents preferred professional attire comparably. CONCLUSIONS AND RELEVANCE: In this study, most patients preferred professional attire for their dermatologists in most settings. It is possible that patients' perceptions of their physicians' knowledge and skill is influenced by the physicians' appearance, and these perceptions may affect outcomes. PMID- 27248429 TI - Validated Predictions of Metabolic Energy Consumption for Submaximal Effort Movement. AB - Physical performance emerges from complex interactions among many physiological systems that are largely driven by the metabolic energy demanded. Quantifying metabolic demand is an essential step for revealing the many mechanisms of physical performance decrement, but accurate predictive models do not exist. The goal of this study was to investigate if a recently developed model of muscle energetics and force could be extended to reproduce the kinematics, kinetics, and metabolic demand of submaximal effort movement. Upright dynamic knee extension against various levels of ergometer load was simulated. Task energetics were estimated by combining the model of muscle contraction with validated models of lower limb musculotendon paths and segment dynamics. A genetic algorithm was used to compute the muscle excitations that reproduced the movement with the lowest energetic cost, which was determined to be an appropriate criterion for this task. Model predictions of oxygen uptake rate (VO2) were well within experimental variability for the range over which the model parameters were confidently known. The model's accurate estimates of metabolic demand make it useful for assessing the likelihood and severity of physical performance decrement for a given task as well as investigating underlying physiologic mechanisms. PMID- 27248430 TI - Quantitative Measurements of Enhancement on Preprocedure Triphasic CT Can Predict Response of Colorectal Liver Metastases to Radioembolization. AB - OBJECTIVE: Colorectal liver metastases (CLM) have a variable response to radioembolization. This may be due at least partly to differences in tumor arterial perfusion. The present study examines whether quantitative measurements of enhancement on preprocedure triphasic CT can be used to predict the response of CLM to radioembolization. MATERIALS AND METHODS: We retrospectively reviewed patients with CLM treated with radioembolization who underwent pretreatment PET/CT and triphasic CT examinations and posttreatment PET/CT examinations. A total of 31 consecutive patients with 60 target tumors were included in the present study. For each tumor, we calculated the hepatic artery coefficient (HAC), portal vein coefficient (PVC), and arterial enhancement fraction (AEF) based on enhancement measurements on pretreatment triphasic CT. HAC and PVC are estimates of the hepatic artery and portal vein blood supply. AEF, which is the arterial phase enhancement divided by the portal phase enhancement, provides an estimate of the hepatic artery blood supply as a fraction of the total blood supply. For each tumor, the metabolic response to radioembolization was based on findings from the initial follow-up PET/CT scan obtained at 4-8 weeks after treatment. RESULTS: A total of 55% of CLM had a complete or partial metabolic response. Arterial phase enhancement, the HAC, and the PVC did not predict which tumors responded to radioembolization. However, the AEF was statistically significantly greater in tumors with a complete or partial metabolic response than in tumors with no metabolic response (i.e., those with stable disease or disease progression) (p = 0.038). An AEF of less than 0.4 was associated with a 40% response rate, whereas an AEF greater than 0.75 was associated with a 78% response rate. CONCLUSION: Response to radioembolization can be predicted using the AEF calculated from the preprocedure triphasic CT. PMID- 27248431 TI - Overview of Innovative Mouse Models for Imaging Neuroinflammation. AB - Neuroinflammation demands a comprehensive appraisal in situ to gain in-depth knowledge on the roles of particular cells and molecules and their potential roles in therapy. Because of the lack of appropriate tools, direct visualization of cells has been poorly investigated up to the present. In this context, reporter mice expressing cell-specific fluorescent proteins, combined with multiphoton microscopy, provide a window into cellular processes in living animals. In addition, the ability to collect multiple fluorescent colors from the same sample makes in vivo microscopy uniquely useful for characterizing many parameters from the same area, supporting powerful correlative analyses. Here, we present an overview of the advantages and limitations of this approach, with the purpose of providing insight into the neuroinflammation field. We also provide a review of existing fluorescent mouse models and describe how these models have been used in studies of neuroinflammation. Finally, the potential for developing advanced genetic tools and imaging resources is discussed. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248432 TI - Intestinal Preparation Techniques for Histological Analysis in the Mouse. AB - The murine intestinal tract represents a difficult organ system to study due to its long convoluted tubular structure, narrow diameter, and delicate mucosa which undergoes rapid changes after sampling prior to fixation. These features do not make for easy histological analysis as rapid fixation in situ, or after simple removal without careful dissection, results in poor postfixation tissue handling and limited options for high quality histological sections. Collecting meaningful quantitative data by analysis of this tissue is further complicated by the anatomical changes in structure along its length. This article describes two methods of intestinal sampling at necropsy that allow systematic histological analysis of the entire intestinal tract, either through examination of cross sections (circumferences) by the gut bundling technique or longitudinal sections by the adapted Swiss roll technique, together with basic methods for data collection. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248433 TI - Mouse Models of Asthma. AB - Allergic asthma is a chronic inflammatory disease of the conducting airways characterized by the presence of allergen-specific IgE, Th2 cytokine production, eosinophilic airway inflammation, bronchial hyperreactivity, mucus overproduction, and structural changes in the airways. Investigators have tried to mimic these features of human allergic asthma in murine models. Whereas the surrogate allergen ovalbumin has been extremely valuable for unravelling underlying mechanisms of the disease, murine asthma models depend nowadays on naturally occurring allergens, such as house dust mite (HDM), cockroach, and Alternaria alternata. Here we describe a physiologically relevant model of acute allergic asthma based on sensitization and challenge with HDM extracts, and compare it with the ovalbumin/alum-induced asthma model. Moreover, we propose a detailed readout of the asthma phenotype, determining the degree of eosinophilia in bronchoalveolar lavage fluids by flow cytometry, visualizing goblet cell metaplasia, and measuring Th cytokine production by lung-draining mediastinal lymph node cells restimulated with HDM. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248434 TI - An Overview of Mouse Models of Nonalcoholic Steatohepatitis: From Past to Present. AB - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world. It is associated with obesity and type 2 diabetes and represents a spectrum of histological abnormalities ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), which can further progress to fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and liver failure. To gain insight into the pathogenesis and evaluate treatment options, mouse models of NAFLD/NASH are of utmost importance. There is a high phenotypical variety in the available mouse models, however, models that truly display the full spectrum of histopathological and metabolic features associated with human NASH are rare. In this review, we summarize the most important NAFLD/NASH mouse models that have been developed over the years and briefly highlight the pros and cons. Also, we illustrate the preclinical research in which these models have been used. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248435 TI - Development of a Representative Mouse Model with Nonalcoholic Steatohepatitis. AB - Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the Western world. It represents a disease spectrum ranging from isolated steatosis to non-alcoholic steatohepatitis (NASH). In particular, NASH can evolve to fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure. The development of novel treatment strategies is hampered by the lack of representative NASH mouse models. Here, we describe a NASH mouse model, which is based on feeding non-genetically manipulated C57BL6/J mice a 'Western style' high fat/high-sucrose diet (HF-HSD). HF-HSD leads to early obesity, insulin resistance, and hypercholesterolemia. After 12 weeks of HF-HSD, all mice exhibit the complete spectrum of features of NASH, including steatosis, hepatocyte ballooning, and lobular inflammation, together with fibrosis in the majority of mice. Hence, this model closely mimics the human disease. Implementation of this mouse model will lead to a standardized setup for the evaluation of (i) underlying mechanisms that contribute to the progression of NAFLD to NASH, and (ii) therapeutic interventions for NASH. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248436 TI - A School-Based Intervention to Increase Lyme Disease Preventive Measures Among Elementary School-Aged Children. AB - PURPOSE: Educational interventions to reduce Lyme disease (LD) among at-risk school children have had little study. The purpose of this study was to evaluate whether a short in-class LD education program based on social learning theory and the Health Belief Model (HBM) impacted a child's knowledge, attitude, and preventive behavior. METHODS: Students in grades 2-5 in 19 elementary schools were selected in an area that was highly endemic for LD. The children received an educational intervention or were on a wait list as controls. Their knowledge, attitudes, and self-reported preventive behaviors were surveyed before implementing the program and 1 year later. General linear regression analyses adjusting for age, gender, and baseline variables were used to measure the impact of the intervention. RESULTS: There were 3570 participants in the study: 1562 received the intervention, and 2008 were controls. The mean age for both groups was 9.1 years, with 53% women in the intervention group and 50% women in the control group. The children in the intervention group increased their overall knowledge of LD more than the children in the control group (overall knowledge score improvement, mean difference (SD) 1.38 (1.3) vs. 0.36 (1.3) p < 0.0001). All children in classes receiving the intervention reported an increase in precautionary behavior, positive attitude toward taking precautions, and self efficacy compared with the wait list controls. Two LD cases were confirmed during the follow-up period, one in the intervention group and one in the controls. CONCLUSIONS: These findings demonstrate that a short in-class educational program that includes elements of the HBM, including: (1) awareness and knowledge about the disease, (2) benefits of preventive behavior, and (3) confidence in ability to perform preventive behaviors can improve knowledge, attitude, and self reported precautionary behavior among at-risk children. www.clinicaltrials.gov : NCT00594997. PMID- 27248437 TI - Correction to "Cyanine-Based Fluorescent Probe for Highly Selective Detection of Glutathione in Cell Cultures and Live Mouse Tissues". PMID- 27248438 TI - Restrictions on the Importation of Zebrafish into Canada Associated with Spring Viremia of Carp Virus. AB - The zebrafish model system is helping researchers improve the health and welfare of people and animals and has become indispensable for advancing biomedical research. As genetic engineering is both resource intensive and time-consuming, sharing successfully developed genetically modified zebrafish lines throughout the international community is critical to research efficiency and to maximizing the millions of dollars in research funding. New restrictions on importation of zebrafish into Canada based on putative susceptibility to infection by the spring viremia of carp virus (SVCV) have been imposed on the scientific community. In this commentary, we review the disease profile of SVCV in fish, discuss the findings of the Canadian government's scientific assessment, how the interpretations of their assessment differ from that of the Canadian research community, and describe the negative impact of these regulations on the Canadian research community and public as it pertains to protecting the health of Canadians. PMID- 27248439 TI - Trehalose pathway as an antifungal target. AB - With an increasing immunocompromised population which is linked to invasive fungal infections, it is clear that our present 3 classes of antifungal agents may not be sufficient to provide optimal management to these fragile patients. Furthermore, with widespread use of antifungal agents, drug-resistant fungal infections are on the rise. Therefore, there is some urgency to develop the antifungal pipeline with the goal of new antifungal agent discovery. In this review, a simple metabolic pathway, which forms the disaccharide, trehalose, will be characterized and its potential as a focus for antifungal target(s) explained. It possesses several important features for development of antifungal agents. First, it appears to have fungicidal characteristics and second, it is broad spectrum with importance across both ascomycete and basidiomycete species. Finally, this pathway is not found in mammals so theoretically specific inhibitors of the trehalose pathway and its enzymes in fungi should be relatively non-toxic for mammals. The trehalose pathway and its critical enzymes are now in a position to have directed antifungal discovery initiated in order to find a new class of antifungal drugs. PMID- 27248440 TI - Angiotensin-Converting Enzyme Inhibition as an Adjunct to Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Epidemiological studies in older individuals have found an association between the use of angiotensin-converting enzyme (ACE) inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength, and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation (PR). OBJECTIVES: To investigate the hypothesis that enalapril, an ACE inhibitor, would augment the improvement in exercise capacity seen during PR. METHODS: We performed a double-blind, placebo-controlled, parallel-group randomized controlled trial. Patients with chronic obstructive pulmonary disease, who had at least moderate airflow obstruction and were taking part in PR, were randomized to either 10 weeks of therapy with an ACE inhibitor (10 mg enalapril) or placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Eighty patients were enrolled, 78 were randomized (age 67 +/- 8 years; FEV1 48 +/- 21% predicted), and 65 completed the trial (34 on placebo, 31 on the ACE inhibitor). The ACE inhibitor-treated group demonstrated a significant reduction in systolic blood pressure (Delta, -16 mm Hg; 95% confidence interval [CI], -22 to -11) and serum ACE activity (Delta, -18 IU/L; 95% CI, -23 to -12) versus placebo (between-group differences, P < 0.0001). Peak power increased significantly more in the placebo group (placebo Delta, +9 W; 95% CI, 5 to 13 vs. ACE-I Delta, +1 W; 95% CI, -2 to 4; between-group difference, 8 W; 95% CI, 3 to 13; P = 0.001). There was no significant between-group difference in quadriceps strength or health-related quality of life. CONCLUSIONS: Use of the ACE inhibitor enalapril, together with a program of PR, in patients without an established indication for ACE-I, reduced the peak work rate response to exercise training in patients with chronic obstructive pulmonary disease. PMID- 27248441 TI - Emerging Waste-to-Energy Technologies: Solid Waste Solution or Dead End? PMID- 27248442 TI - Nonlinear thermoelectric transport in single-molecule junctions: the effect of electron-phonon interactions. AB - In this paper, we theoretically analyze steady-state thermoelectric transport through a single-molecule junction with a vibrating bridge. The thermally induced charge current in the system is explored using a nonequilibrium Green function formalism. We study the combined effects of Coulomb interactions between charge carriers on the bridge and electron-phonon interactions on the thermocurrent beyond the linear response regime. It is shown that electron-vibron interactions may significantly affect both the magnitude and the direction of the thermocurrent, and vibrational signatures may appear. PMID- 27248443 TI - In Situ Detection of Protein Complexes and Modifications by Chemical Ligation Proximity Assay. AB - Protein function is often regulated by protein-protein interactions and post translational modifications. Detection of these important biological phenomena in fixed biological samples could serve as an invaluable tool in biomedical research, drug development, as well as clinical cancer diagnostics and prognostics. We report here a novel methodology which utilizes unique antibody bioconjugates capable of forming proximity induced chemical ligation to enable in situ detection of proximal targets in fixed biological samples. Using this new methodology, we demonstrate in situ visualization of various protein heterodimers/complexes and post-translational modifications such as phosphorylation and ubiquitination. This new method offers high specificity, sensitivity, flexibility, and ease of use. In addition, the assay preserves critical contextual and heterogeneity information on biomarkers in clinically relevant samples. PMID- 27248444 TI - Charting variability to ensure conceptual and design precision: a comment on Ogden (2016). PMID- 27248445 TI - A Legal Setback for the Affordable Care Act. PMID- 27248446 TI - Stunted growth. PMID- 27248447 TI - Monte Carlo simulation of body height in a spatial network. PMID- 27248459 TI - Spectroscopic probe to contribution of physicochemical transformations in the toxicity of aged ZnO NPs to Chlorella vulgaris: new insight into the variation of toxicity of ZnO NPs under aging process. AB - Zinc oxide nanoparticles (ZnO NPs) are one of the most abundantly applied nanomaterials in nanotechnology-based industries and they may cause unexpected environmental and health risks with their physicochemical transformations in the environment. Currently, there is still a lack of the in-depth understanding of the toxicity of aged ZnO NPs to aquatic organisms, particularly demanding quantitative analysis of the physicochemical transformations to distinguish their contributions in the toxicity assessment. For this purpose, therefore, we initiated the study of the toxicity of aged ZnO NPs to the model aquatic microalga, i.e. Chlorella vulgaris, and with the aid of spectroscopic tools for characterization and quantification of the physicochemical transformations, we scrutinized the toxicity variations for ZnO NPs with different aging times. As a result, we found that the toxicity altered in an abnormal manner with the aging time, i.e. the toxicity of aged ZnO NPs for 30 days showed the higher toxicity to the green alga than the fresh ZnO NPs or the ZnO NPs aged for longer time (e.g. 120 and 210 days). Through spectroscopic tools such as XRD, FTIR and Raman spectroscopy, we made both the qualitative and quantitative assessments of the physicochemical changes of the ZnO NPs, and confirmed that in the early stage, the toxicity mainly stemmed from the release of zinc ions, but with longer aging time, the neoformation of the nanoparticles played the critical role, leading to the overall reduced toxicity due to the less toxic hydrozincite and zinc hydroxide in the transformed compounds. PMID- 27248460 TI - Cardiac replacement therapies: outcomes and costs for heart transplantation versus circulatory assist. AB - OBJECTIVES: Growing number of patients with terminal heart failure and a shortage of heart donors have increased use of short- and long-term mechanical circulatory support (MCS). Few studies have analyzed survival rates and healthcare costs for heart transplantation (HTx), with or without extracorporeal membrane oxygenation (ECMO) and left ventricular assist device (LVAD). DESIGN: In a retrospective, single-center study, data were analyzed from patients listed for HTx who died on the waiting list (DWL, n = 12), underwent HTx (n = 206), had ECMO as bridge to HTx (ECHTx, n = 15), or received LVAD treatment, either isolated (LVAD, n = 19) or bridging to HTx (LVADHTx, n = 26) during 2005-2012. Survival and hospital costs were assessed. RESULTS: One- and five-year survival rates were 96% and 83% for the LVADHTx group, 92% and 81% for HTx, 70% and 70% for ECHTx, 48% and 36% for LVAD and 0% for the DWL group (overall survival, p < 0.001). Total hospital cost at one year was $102,101 +/- 202,604 for DWL, $151,685 +/- 86,892 for HTx, $292,078 +/- 101,915 for ECHTx, $427,337 +/- 365,154 for LVAD, and $600,897 +/- 198,109 for LVADHTx. CONCLUSION: The LVADHTx and HTx groups showed excellent one- and five-year survival. The combined group of DWL and HTx patients had similar survival to the combined groups of MCS, but use of LVAD pre-transplant quadrupled the cost. PMID- 27248461 TI - Hepatorenal syndrome in cirrhosis: diagnostic, pathophysiological, and therapeutic aspects. AB - INTRODUCTION: Renal failure is a common and serious complication in cirrhosis and represents a wide spectrum of etiologies. The hepatorenal syndrome (HRS) represents a distinct type of renal failure, only seen in cirrhotic patients with ascites. The diagnostic criteria, knowledge in the pathophysiology of renal failure and HRS, and treatment hereof, have evolved tremendously during the last decades, and it is the aim of this review to summarize these discoveries. AREAS COVERED: The focus will primarily be on treatment and prevention of renal failure and HRS, but areas concerning definition, diagnosis, including biomarkers, and pathophysiology, will also be covered through a comprehensive, critical reading of the latest literature, encompassing the most recent, updated, international guidelines, reviews and high-impact original literature. Expert commentary: The advances made in the understanding of the pathophysiology of HRS and other complications of cirrhosis within the recent decades, have provided the basis for improved diagnostic criteria and the development of treatments that have substantially increased survival rates in cirrhotic patients suffering from these conditions. Focus should, in the nearest future, be on continuing this positive development, thus further improving prognosis for cirrhotic patients with HRS. PMID- 27248462 TI - In Situ Confinement of Ultrasmall Pd Clusters within Nanosized Silicalite-1 Zeolite for Highly Efficient Catalysis of Hydrogen Generation. AB - Well-dispersed and ultrasmall Pd clusters in nanosized silicalite-1 (MFI) zeolite have been prepared under direct hydrothermal conditions using [Pd(NH2CH2CH2NH2)2]Cl2 as precursor. High-resolution scanning transmission electron microscopy studies indicate that the Pd clusters are encapsulated within the intersectional channels of MFI, and the Pd clusters in adjacent channels visually aggregate, forming nanoparticles (NPs) of ~1.8 nm. The resultant catalysts show an excellent activity and highly efficient H2 generation toward the complete decomposition of formic acid (FA) under mild conditions. Notably, thanks to the further reduced Pd NP size (~1.5 nm) and the additionally introduced basic sites, the Pd/S-1-in-K catalyst affords turnover frequency values up to 856 h(-1) at 25 degrees C and 3027 h(-1) at 50 degrees C. The easy in situ confinement synthesis of metal clusters in zeolites endows the catalysts with superior catalytic activities, excellent recyclability, and high thermal stability, thus opening new perspectives for the practical application of FA as a viable and effective H2 storage material for use in fuel cells. PMID- 27248463 TI - Nanomaterial resistant microorganism mediated reduction of graphene oxide. AB - In this study, soil bacteria were isolated from nanomaterials (NMs) contaminated pond soil and enriched in the presence of graphene oxide (GO) in mineral medium to obtain NMs resistant bacteria. The isolated resistant bacteria were biochemically and genetically identified as Fontibacillus aquaticus. The resistant bacteria were allowed to interact with engineered GO in order to study the biotransformation in GO structure. Raman spectra of GO extracted from culture medium revealed decreased intensity ratio of ID/IG with subsequent reduction of CO which was consistent with Fourier transform infrared (FTIR) results. The structural changes and exfoliatied GO nanosheets were also evident from transmission electron microscopy (TEM) images. Ultraviolet-visible spectroscopy, high resolution X-ray diffraction (XRD) and current-voltage measurements confirmed the reduction of GO after the interaction with resistant bacteria. X ray photoelectron spectroscopy (XPS) analysis of biotransformed GO revealed reduction of oxygen-containing species on the surface of nanosheets. Our results demonstrated that the presented method is an environment friendly, cost effective, simple and based on green approaches for the reduction of GO using NMs resistant bacteria. PMID- 27248464 TI - Spironolactone loaded nanostructured lipid carrier gel for effective treatment of mild and moderate acne vulgaris: A randomized, double-blind, prospective trial. AB - Spironolactone (SP) known as an anti-androgen drug, has been proven to be effective in treatment of acne. The quest to minimize the unnecessary systemic side effects associated with the oral drug administration of spironolactone, has led to a growing interest of loading SP on lipid nanoparticles to deliver the drug in a topical formulation. The aim of the current investigation was to prepare and compare the performance of SP loaded nanostructured lipid carrier (SP NLC) and SP alcoholic gels (SP-ALC) on two groups of respective patient populations, group A and group B in the treatment of mild to moderate acne vulgaris. The results showed that SP-NLCs were spherical in shape with an average diameter of ~240nm. The polydispersity index (PI) and zeta potential of these nanoparticles were 0.286 and -21.4 respectively. The gels showed non-Newtonian independent pseudoplastic and shear thinning behavior. The SP-NLCs was not toxic to fibroblast cell strains at the 24 and 48h periods. Results showed that the mean number of total lesions (37.66+/-9.27) and non-inflammatory lesions (29.26+/ 7.99) in group A significantly decreased to 20.31+/-6.58 (p<0.05) and to 13.95+/ 5.22 (p<0.05) respectively. A similar pattern was observed for group B where the mean number of total lesions and non-inflammatory lesions reduced from 33.73+/ 9.40 to 19.13+/-5.53 (p<0.05) and from 25.65+/-8.12 to 13.45+/-4.48 (p<0.05) respectively. The total lesion count (TLC) was significantly decreased from 37.16+/-9.28 to 19.63+/-6.36 (for group A; p<0.071) and 32.60+/-9.32 to 18.33+/ 5.55 (for group B; p<0.05) respectively. After treatment with SP-NLC for 8 weeks, the water content of the skin significantly (p<0.05) increased from 37.44+/-8.85 to 45.69+/-19.34 instrumental units. Therefore, the SP-NLC gel may help in controlling acne vulgaris with skin care benefits. PMID- 27248465 TI - Zero-Point Spin-Fluctuations of Single Adatoms. AB - Stabilizing the magnetic signal of single adatoms is a crucial step toward their successful usage in widespread technological applications such as high-density magnetic data storage devices. The quantum mechanical nature of these tiny objects, however, introduces intrinsic zero-point spin-fluctuations that tend to destabilize the local magnetic moment of interest by dwindling the magnetic anisotropy potential barrier even at absolute zero temperature. Here, we elucidate the origins and quantify the effect of the fundamental ingredients determining the magnitude of the fluctuations, namely, the (i) local magnetic moment, (ii) spin-orbit coupling, and (iii) electron-hole Stoner excitations. Based on a systematic first-principles study of 3d and 4d adatoms, we demonstrate that the transverse contribution of the fluctuations is comparable in size to the magnetic moment itself, leading to a remarkable ?50% reduction of the magnetic anisotropy energy. Our analysis gives rise to a comprehensible diagram relating the fluctuation magnitude to characteristic features of adatoms, providing practical guidelines for designing magnetically stable nanomagnets with minimal quantum fluctuations. PMID- 27248466 TI - Childhood victimization and HIV risk behaviors among university students in Saint Petersburg, Russia. AB - Exposure to childhood victimization and abuse has been shown to affect HIV risk in adult populations. In Russia, the existence of child abuse was largely unrecognized until 1990s and its behavioral consequences remain understudied. Our goal was to assess childhood victimization and HIV risk behavior among young adults in Saint-Petersburg, Russia: 743 students from 15 local universities were surveyed. Unprotected sexual intercourse was the most common type of HIV risk behavior: study participants reported no condom use at last intercourse (65.17%), inconsistent condom use (58.43%) and 30.81% never used condoms in the past 3 months. Childhood sexual victimization was significantly associated with unprotected sex at last intercourse and with inconsistent condom use in the past 3 months. Young adults in Russia are vulnerable to HIV epidemic due to the pervasiveness of unprotected sexual intercourse, and childhood sexual victimization is associated with risky sexual behavior in this population. Efforts to combat HIV epidemic in Russia must include programming for the prevention of childhood sexual abuse and the development of services for the survivors of childhood victimization. PMID- 27248467 TI - A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy. AB - PURPOSE: This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). METHOD: 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. RESULTS: Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. CONCLUSIONS: DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT induced brain vasculature damages. PMID- 27248468 TI - miRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers. AB - As in many cancer types, miRNA expression profiles and functions have become an important field of research on non-medullary thyroid carcinomas, the most common endocrine cancers. This could lead to the establishment of new diagnostic tests and new cancer therapies. However, different studies showed important variations in their research strategies and results. In addition, the action of miRNAs is poorly considered as a whole because of the use of underlying dogmatic truncated concepts. These lead to discrepancies and limits rarely considered. Recently, this field has been enlarged by new miRNA functional and expression studies. Moreover, studies using next generation sequencing give a new view of general miRNA differential expression profiles of papillary thyroid carcinoma. We analyzed in detail this literature from both physiological and differential expression points of view. Based on explicit examples, we reviewed the progresses but also the discrepancies and limits trying to provide a critical approach of where this literature may lead. We also provide recommendations for future studies. The conclusions of this systematic analysis could be extended to other cancer types. PMID- 27248469 TI - Overexpression of transient receptor potential mucolipin-2 ion channels in gliomas: role in tumor growth and progression. AB - The Transient Receptor Potential (TRP) superfamily consists of cation-selective and non-selective ion channels playing an important role both in sensory physiology and in physiopathology in several complex diseases including cancers. Among TRP family, the mucolipin (TRPML1, -2, and -3) channels represent a distinct subfamily of endosome/lysosome Ca2+ channel proteins. Loss-of-function mutations in human TRPML-1 gene cause a neurodegenerative disease, Mucolipidosis Type IV, whereas at present no pathology has been associated to human TRPML-2 channels. Herein we found that human TRPML-2 is expressed both in normal astrocytes and neural stem/progenitor cells. By quantitative RT-PCR, western blot, cytofluorimetric and immunohistochemistry analysis we also demonstrated that TRPML-2 mRNA and protein are expressed at different levels in glioma tissues and high-grade glioma cell lines of astrocytic origin. TRPML-2 mRNA and protein levels increased with the pathological grade, starting from pylocitic astrocytoma (grade I) to glioblastoma (grade IV). Moreover, by RNA interference, we demonstrated a role played by TRPML-2 in survival and proliferation of glioma cell lines. In fact, knock-down of TRPML-2 inhibited the viability, altered the cell cycle, reduced the proliferation and induced apoptotic cell death in glioma cell lines. The DNA damage and apoptosis induced by TRPML-2 loss increased Ser139 H2AX phosphorylation and induced caspase-3 activation; furthermore, knock-down of TRPML-2 in T98 and U251 glioma cell lines completely abrogated Akt and Erk1/2 phosphorylation, as compared to untreated cells. Overall, the high TRPML-2 expression in glioma cells resulted in increased survival and proliferation signaling, suggesting a pro-tumorigenic role played by TRPML-2 in glioma progression. PMID- 27248471 TI - The Hippo transducers TAZ/YAP and their target CTGF in male breast cancer. AB - Male breast cancer (MBC) is a rare disease and its biology is poorly understood. Deregulated Hippo pathway promotes oncogenic functions in female breast cancer. We herein investigated the expression of the Hippo transducers TAZ/YAP and their target CTGF in MBC. Tissue microarrays containing samples from 255 MBC patients were immunostained for TAZ, YAP and CTGF. One hundred and twenty-nine patients were considered eligible. The Pearson's Chi-squared test of independence was used to test the association between categorical variables. The correlation between TAZ, YAP and CTGF was assessed with the Pearson's correlation coefficient. The Kaplan-Meier method and the log-rank test were used for estimating and comparing survival curves. Cox proportional regression models were built to identify variables impacting overall survival. Statistical tests were two-sided. Tumors were considered to harbor active TAZ/YAP-driven gene transcription when they co expressed TAZ, or YAP, and CTGF. Patients whose tumors had the TAZ/CTGF and YAP/CTGF phenotypes experienced shorter overall survival compared with their negative counterparts (log rank p = 0.036 for both). TAZ/CTGF and YAP/CTGF tumors were associated with decreased survival in patients with invasive ductal carcinomas, G3 tumors, hormone receptor-positive tumors, and tumors with elevated Ki-67. Multivariate analyses confirmed that the TAZ/CTGF and YAP/CTGF phenotypes are independent predictors of survival (HR 2.03, 95% CI: 1.06-3.90, p = 0.033; and HR 2.00, 95% CI: 1.04-3.84, p = 0.037 respectively). Comparable results were obtained when excluding uncommon histotypes (TAZ/CTGF: HR 2.34, 95% CI: 1.16 4.73, p = 0.018. YAP/CTGF. HR 2.36, 95% CI: 1.17-4.77, p = 0.017). Overall, the TAZ/YAP-driven oncogenic program may be active in MBC, conferring poorer survival. PMID- 27248472 TI - AKR1B10 promotes breast cancer metastasis through integrin alpha5/delta-catenin mediated FAK/Src/Rac1 signaling pathway. AB - Aldo-keto reductase 1B10 (AKR1B10) is not expressed in normal breast, but upregulated in primary and metastatic breast cancers, being a negative prognostic factor. This study characterized the molecular mechanisms of AKR1B10-promoted breast cancer metastasis. Ectopic expression of AKR1B10 in breast cancer cells MCF-7 and MDA-MB-231 or siRNA-mediated silencing in BT-20 cells affected cell adhesion, migration and invasion in cell culture, and metastasis to the lung in the nude mice through upregulation of integrin alpha5 and delta-catenin. Silencing of integrin alpha5 or delta-catenin eradicated the cell adhesion and migration enhanced by AKR1B10, both of which acted synergistically. In these cells, the integrin alpha5 mediated focal adhesion kinase (FAK) signaling pathway was activated by AKR1B10, which, along with delta-catenin, stimulated Rac1 mediated cell migration and movement. In human primary and lymph node metastatic breast cancer, AKR1B10, integrin alpha5 and delta-catenin were correlatively upregulated with r=0.645 (p<0.0001) and r=0.796 (p<0.0001), respectively. These data suggest that AKR1B10 promotes breast cancer metastasis through activation of the integrin alpha5 and delta-catenin mediated FAK/Src/Rac1 signaling pathway. PMID- 27248473 TI - Recurrent, truncating SOX9 mutations are associated with SOX9 overexpression, KRAS mutation, and TP53 wild type status in colorectal carcinoma. AB - PURPOSE: The extent to which the developmental transcription factor SOX9 functions as an oncogene or tumor suppressor in colorectal carcinoma (CRC) is debatable. We aimed to clarify the effect of SOX9 mutations on SOX9 protein expression and their association with known molecular subtypes and clinical characteristics in advanced CRC. EXPERIMENTAL DESIGN: Next generation sequencing data (MSK-IMPACT) from CRC patients was used to interrogate SOX9, KRAS, NRAS, BRAF, TP53, APC, and PIK3CA. Mutant and wild type (WT) SOX9 cases underwent immunohistochemical (IHC) staining to assess protein expression. SOX9 allele specific copy number was assessed by Affymetrix Oncoscan array. RESULTS: SOX9 was mutated in 38 of 353 (10.7%) CRC, of which 82% were frameshift or nonsense. Compared to SOX9 WT, SOX9 mutation was strongly associated with coexistent mutant KRAS (p=0.0001) and WT TP53 (p=0.0004). SOX9 was overexpressed in both SOX9 mutant and WT CRC. Among SOX9 mutants, the highest expression was noted for truncating exon 3 mutants (mean H scores 239+/-105 versus 147+/-119, p value=0.02). Further, SOX9 truncating mutants with loss of the WT allele demonstrated protein overexpression indicating the WT protein was not required for protein stabilization. CONCLUSIONS: SOX9 is overexpressed in CRC, including those with recurrent distal truncating mutations. The latter has structural similarity to the oncogenic isoform MiniSOX9, which is distally truncated due to aberrant splicing. This information suggests that truncated SOX9 has oncogenic features. SOX9 mutations are highly enriched in KRAS mutant and TP53 wild type CRC; and may provide a therapeutic target in approximately 11% of CRC. PMID- 27248474 TI - Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis. AB - Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/ C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients. PMID- 27248475 TI - Toxicological assessment of multi-walled carbon nanotubes in vitro: potential mitochondria effects on male reproductive cells. AB - Multi-walled carbon nanotubes (MWCNTs) have been widely used in many fields and were reported to cause reversible testis damage in mice at high-dose. However the reproductive effects of low dose MWCNTs remained elusive. Herein, we used the mice spermatocyte cell line (GC-2spd) to assess the reproductive effects of MWCNTs. Size distribution, zeta potential, and intensity of MWCNTs were characterized. A maximal concentration of 0.5 MUg/mL MWCNTs was found to be nonlethal to GC-2spd. At this dose, cell cycles and the ROS levels were in normal status. We also found MWCNTs accumulated in mitochondria, which caused potential mitochondrial DNA damage in spermatocyte. Furthermore, the expression level of mitochondria-related genes, the oxygen consumption rate, and cellular ATP content were declined compared to controls, even at the nonlethal dose. Our results suggested for the first time that, in germ cells, mitochondrion was a cellular organelle that accumulated MWCNTs. PMID- 27248477 TI - Polythiophene-Wrapped Olivine NaFePO4 as a Cathode for Na-Ion Batteries. AB - The surface of olivine NaFePO4 was modified with polythiophene (PTh) to develop a high-performance cathode material for use in Na-ion batteries. The Rietveld refinement results of the prepared material reveal that PTh-coated NaFePO4 belongs to a space group of Pnma with lattice parameters of a = 10.40656 A, b = 6.22821 A, and c = 4.94971 A. Uncoated NaFePO4 delivers a discharge capacity of 108 mAh g(-1) at a current density of 10 mA g(-1) within a voltage range of 2.2 4.0 V. Conversely, the PTh-coated NaFePO4 electrode exhibits significantly improved electrochemical performance, where it exhibits a discharge capacity of 142 mAh g(-1) and a stable cycle life over 100 cycles, with a capacity retention of 94%. The NaFePO4/PTh electrode also exhibits satisfactory performance at high current densities, and reversible capacities of 70 mAh g(-1) at 150 mA g(-1) and 42 mAh g(-1) at 300 mA g(-1) are obtained compared with negligible capacities without coating. The related electrochemical reaction mechanism has been investigated using in situ X-ray absorption spectroscopy (XAS), which revealed a systematic change of Fe valence and reversible contraction/expansion of Fe-O octahedra upon desodiation/sodiation. The ex situ X-ray diffraction (XRD) results suggest that the deintercalation in NaFePO4/PTh electrodes proceeds through a stable intermediate phase and the lattice parameters show a reversible contraction/expansion of unit cell during cycling. PMID- 27248476 TI - The protective effect of longer duration of breastfeeding against pregnancy associated triple negative breast cancer. AB - Parity associated breast cancer (PABC) often diagnosed within the 2-5 years after a full term pregnancy. PABC is usually present with more advanced, poorly differentiated, high-grade cancers that show shorter time to progression and often of the triple negative breast cancer (TNBC) subtype. Data from around the world show that pregnancy-associated TNBC is independently associated with poor survival, underscoring the impact of the pregnant breast microenvironment on the biology and consequently the prognosis of these tumors. Although it is not yet clear, a link between pregnancy-associated TNBCs and lack or shorter duration of breastfeeding (not pregnancy per se) has been proposed. Here, we present epidemiological and experimental evidence for the protective effect of longer duration of lactation against pregnancy-associated TNBCs, and propose a putative molecular mechanism for this protective effect and its effect in eliminating any potential TNBC precursors from the breast by the end of the natural breast involution. PMID- 27248478 TI - Elucidation of Nonadditive Effects in Protein-Ligand Binding Energies: Thrombin as a Case Study. AB - Accurate predictions of free energies of binding of ligands to proteins are challenging partly because of the nonadditivity of protein-ligand interactions; i.e., the free energy of binding is the sum of numerous enthalpic and entropic contributions that cannot be separated into functional group contributions. In principle, molecular simulations methodologies that compute free energies of binding do capture nonadditivity of protein-ligand interactions, but efficient protocols are necessary to compute well-converged free energies of binding that clearly resolve nonadditive effects. To this end, an efficient GPU-accelerated implementation of alchemical free energy calculations has been developed and applied to two congeneric series of ligands of the enzyme thrombin. The results show that accurate binding affinities are computed across the two congeneric series and positive coupling between nonpolar R(1) substituents and a X = NH3(+) substituent is reproduced, albeit with a weaker trend than experimentally observed. By contrast, a docking methodology completely fails to capture nonadditive effects. Further analysis shows that the nonadditive effects are partly due to variations in the strength of a hydrogen-bond between the X = NH3(+) ligands family and thrombin residue Gly216. However, other partially compensating interactions occur across the entire binding site, and no single interaction dictates the magnitude of the nonadditive effects for all the analyzed protein-ligand complexes. PMID- 27248479 TI - Stereoselective Metabolism of the Sterol Biosynthesis Inhibitor Fungicides Fenpropidin, Fenpropimorph, and Spiroxamine in Grapes, Sugar Beets, and Wheat. AB - Metabolism of chiral pesticides in crops is typically studied using achiral analytical methods and, consequently, the stereoisomer composition of residues is unknown. In this study, we developed an enantioselective GC-MS/MS method to quantify residues of the fungicides fenpropidin, fenpropimorph, and spiroxamine in plant matrices. In field trials, the fungicides were applied to grapevines, sugar beets, or wheat. Fenpropidin was metabolized with no or only weak enantioselectivity. For fenpropimorph, slightly enantioselective metabolism was observed in wheat but more pronounced in sugar beets. This enantioselectivity was due to different rates of metabolism and not due to interconversion of enantiomers. The four stereoisomers of spiroxamine were also metabolized at different rates, but selectivity was only found between diastereomers and not between enantiomers. trans-Spiroxamine was preferentially degraded in grapes and cis-spiroxamine in wheat. These findings may affect the consumer dietary risk assessment because toxicological end points were determined using racemic test substances. PMID- 27248480 TI - Cyclic peptide-based potent human SIRT6 inhibitors. AB - We discovered in the current study that six side chain-to-side chain cyclic pentapeptides harboring a central N(epsilon)-dodecyl (or tetradecyl) thiocarbamoyl-lysine residue all behaved as highly potent (nM level) inhibitors against human SIRT6-catalyzed deacylation reaction. Moreover, one compound was also found to be selective for SIRT6 versus SIRT2/3/5 (~20-, ~11-, and >940-fold, respectively), despite its modest (~2.3-fold) SIRT6 inhibitory selectivity versus SIRT1. These compounds could be valuable leads for the identification of further potent and selective human SIRT6 inhibitors. PMID- 27248482 TI - Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia. AB - INTRODUCTION: Anti-sense oligonucleotide (ASO) therapies are a new development in clinical pharmacology offering greater specificity compared to small molecule inhibitors and the ability to target intracellular process' not susceptible to antibody-based therapies. AREAS COVERED: This article reviews the chemical biology of ASOs and related RNA therapeutics. It then reviews the data on their use to treat hyperlipidaemia. Data on mipomersen - an ASO to apolipoprotein B 100(apoB) licensed for treatment of homozygous familial hypercholesterolaemia (FH) is presented. Few effective therapies are available to reduce atehrogenic lipoprotein (a) levels. An ASO therapy to apolipoprotein(a) (ISIS Apo(a)Rx) specifically reduced lipoprotein (a) levels by up to 78%. Treatment options for patients with familial chylomicronaemia syndrome (lipoprotein lipase deficiency; LPLD) or lipodystrophies are highly limited and often inadequate. Volanesorsen, an ASO to apolipoprotein C-3, shows promise in the treatment of LPLD and severe hypertriglyceridaemia as it increases clearance of triglyceride-rich lipoproteins and can normalise triglycerides in these patients. EXPERT OPINION: The uptake of the novel ASO therapies is likely to be limited to selected niche groups or orphan diseases. These will include homozygous FH, severe heterozygous FH for mipomersen; LPLD deficiency and lipodystrophy syndromes for volanesorsen and treatment of patients with high elevated Lp(a) levels. PMID- 27248490 TI - Early-life epileptic encephalopathy secondary to SZT2 pathogenic recessive variants. AB - Advances in genetic testing have led to the identification of increasing numbers of novel gene mutations that underlie infantile-onset epileptic encephalopathies. Recently, a mutagenesis screen identified a novel gene, SZT2, with no known protein function that has been linked to epileptogenesis in mice. Thus far, two clinical reports have identified children with different recessive mutations in SZT2 and varying clinical phenotypes. One case report described patients with epileptic encephalopathy and the other noted patients with cognitive deficiencies, but normal MRI and no epilepsy. This case report identifies novel mutations (a compound heterozygous frameshift and a nonsense variant) in the SZT2 gene with distinct clinical and radiographic findings relative to those previously reported. Our patient presented with intractable epilepsy at 2 months of age. Seizures were refractory to numerous antiepileptic medications and the patient finally achieved seizure cessation at age 3 years with a combination of divalproex and lamotrigine. Our patient had similar facial dysmorphisms (macrocephaly, high forehead, and down-slanted palpebral fissures) to a previous case with truncating mutation. While developmental delay and cognitive deficiencies were present, our case had unique MRI findings suggesting migrational abnormalities not previously reported in other cases. PMID- 27248491 TI - Improving Psychological Measurement: Does It Make a Difference? A Comment on Nesselroade and Molenaar (2016). AB - Nesselroade and Molenaar advocate the use of an idiographic filter approach. This is a fixed-effects approach, which may limit the number of individuals that can be simultaneously modeled, and it is not clear how to model the presence of subpopulations. Most important, Nesselroade and Molenaar's proposal appears to be best suited for modeling long time series on a few variables for a few individuals. Long time series are not common in psychological applications. Can it be applied to the usual longitudinal data we face? These are characterized by short time series (four to five points in time), hundreds of individuals, and dozens of variables. If so, what do we gain? Applied settings most often involve between-individual decisions. I conjecture that their approach will not outperform common, simpler, methods. However, when intraindividual decisions are involved, their approach may have an edge. PMID- 27248493 TI - Institutionalize Reciprocity to Overcome the Public Goods Provision Problem. AB - Cooperation is fundamental to human societies, and one of the important paths for its emergence and maintenance is reciprocity. In prisoner's dilemma (PD) experiments, reciprocal strategies are often effective at attaining and maintaining high cooperation. In many public goods (PG) games or n-person PD experiments, however, reciprocal strategies are not successful at engendering cooperation. In the present paper, we attribute this difficulty to a coordination problem against free riding among reciprocators: Because it is difficult for the reciprocators to coordinate their behaviors against free riders, this may lead to inequality among players, which will demotivate them from cooperating in future rounds. We propose a new mechanism, institutionalized reciprocity (IR), which refers to embedding the reciprocal strategy as an institution (i.e., institutionalizing the reciprocal strategy). We experimentally demonstrate that IR can prevent groups of reciprocators from falling into coordination failure and achieve high cooperation in PG games. In conclusion, we argue that a natural extension of the present study will be to investigate the possibility of IR to serve as a collective punishment system. PMID- 27248492 TI - Cannabinoid Receptors Are Overexpressed in CLL but of Limited Potential for Therapeutic Exploitation. AB - The cannabinoid receptors 1 and 2 (CNR1&2) are overexpressed in a variety of malignant diseases and cannabinoids can have noteworthy impact on tumor cell viability and tumor growth. Patients diagnosed with chronic lymphocytic leukemia (CLL) present with very heterogeneous disease characteristics translating into highly differential risk properties. To meet the urgent need for refinement in risk stratification at diagnosis and the search for novel therapies we studied CNR expression and response to cannabinoid treatment in CLL. Expression levels of CNR1&2 were determined in 107 CLL patients by real-time PCR and analyzed with regard to prognostic markers and survival. Cell viability of primary CLL cells was determined in suspension and co-culture after incubation in increasing cannabinoid concentrations under normal and reduced serum conditions and in combination with fludarabine. Impact of cannabinoids on migration of CLL cells towards CXCL12 was determined in transwell plates. We found CNR1&2 to be overexpressed in CLL compared to healthy B-cells. Discriminating between high and low expressing subgroups, only high CNR1 expression was associated with two established high risk markers and conferred significantly shorter overall and treatment free survival. Viability of CLL primary cells was reduced in a dose dependent fashion upon incubation with cannabinoids, however, healthy cells were similarly affected. Under serum reduced conditions, no significant differences were observed within suspension and co-culture, respectively, however, the feeder layer contributed significantly to the survival of CLL cells compared to suspension culture conditions. No significant differences were observed when treating CLL cells with cannabinoids in combination with fludarabine. Interestingly, biologic activity of cannabinoids was independent of both CNR1&2 expression. Finally, we did not observe an inhibition of CXCL12-induced migration by cannabinoids. In contrast to other tumor entities, our data suggest a limited usability of cannabinoids for CLL therapy. Nonetheless, we could define CNR1 mRNA expression as novel prognostic marker. PMID- 27248494 TI - An Analysis of Water Collection Labor among Women and Children in 24 Sub-Saharan African Countries. AB - BACKGROUND: It is estimated that more than two-thirds of the population in sub Saharan Africa (SSA) must leave their home to collect water, putting them at risk for a variety of negative health outcomes. There is little research, however, quantifying who is most affected by long water collection times. OBJECTIVES: This study aims to a) describe gender differences in water collection labor among both adults and children (< 15 years of age) in the households (HHs) that report spending more than 30 minutes collecting water, disaggregated by urban and rural residence; and b) estimate the absolute number of adults and children affected by water collection times greater than 30 minutes in 24 SSA countries. METHODS: We analyzed data from the Demographic Health Survey (DHS) and the Multiple Indicator Cluster Survey (MICS) (2005-2012) to describe water collection labor in 24 SSA countries. RESULTS: Among households spending more than 30 minutes collecting water, adult females were the primary collectors of water across all 24 countries, ranging from 46% in Liberia (17,412 HHs) to 90% in Cote d'Ivoire (224,808 HHs). Across all countries, female children were more likely to be responsible for water collection than male children (62% vs. 38%, respectively). Six countries had more than 100,000 households (HHs) where children were reported to be responsible for water collection (greater than 30 minutes): Burundi (181,702 HHs), Cameroon (154,453 HHs), Ethiopia (1,321,424 HHs), Mozambique (129,544 HHs), Niger (171,305 HHs), and Nigeria (1,045,647 HHs). CONCLUSION: In the 24 SSA countries studied, an estimated 3.36 million children and 13.54 million adult females were responsible for water collection in households with collection times greater than 30 minutes. We suggest that accessibility to water, water collection by children, and gender ratios for water collection, especially when collection times are great, should be considered as key indicators for measuring progress in the water, sanitation and hygiene sector. PMID- 27248495 TI - Study of Association between Pre-Senile Cataracts and the Polymorphisms rs2228000 in XPC and rs1042522 in p53 in Spanish Population. AB - PURPOSE: To determine if the presence of certain polymorphisms in the DNA repair gene XPC and the apoptosis inductor gene p53 is associated with pre-senile cataract development. METHODS: We have performed a retrospective study over three groups of patients. The group with pre-senile cataract formed by 72 patients younger than 55 with cataract surgery. The group with senile cataract formed by 101 patients older than 55 with cataract surgery. The group without cataract was formed by 42 subjects older than 55 without lens opacities. We analyzed the presence of SNP rs2228000 from XPC and rs1042522 from p53; and the relationship between risk factors such as smoking, alcohol intake, hypertension or diabetes. RESULTS: The comparison of the genotype distribution in XPC, within the different groups, did not show any statistically significant association in any of our analysis (p>0,05). The comparison of the genotype distribution in p53 within the different groups did not show any statistically significant association (p>0,05); except for the comparison between the pre-senile cataract group and the group with senile cataract where the genotype Pro/Pro (C/C) in the recessive inheritance model showed a higher risk for developing pre-senile cataract (p = 0,031; OR = 1.04-15.97). This association decreased when we performed the analysis adjusting by the studied risk factors (p = 0.056). CONCLUSIONS: Allelic variants in the gene XPC are not associated with an increased risk for developing pre-senile cataract. The presence of the genotype Pro/Pro in p53 might be associated with a major risk for developing pre-senile cataract. PMID- 27248496 TI - WDR76 Co-Localizes with Heterochromatin Related Proteins and Rapidly Responds to DNA Damage. AB - Proteins that respond to DNA damage play critical roles in normal and diseased states in human biology. Studies have suggested that the S. cerevisiae protein CMR1/YDL156w is associated with histones and is possibly associated with DNA repair and replication processes. Through a quantitative proteomic analysis of affinity purifications here we show that the human homologue of this protein, WDR76, shares multiple protein associations with the histones H2A, H2B, and H4. Furthermore, our quantitative proteomic analysis of WDR76 associated proteins demonstrated links to proteins in the DNA damage response like PARP1 and XRCC5 and heterochromatin related proteins like CBX1, CBX3, and CBX5. Co immunoprecipitation studies validated these interactions. Next, quantitative imaging studies demonstrated that WDR76 was recruited to laser induced DNA damage immediately after induction, and we compared the recruitment of WDR76 to laser induced DNA damage to known DNA damage proteins like PARP1, XRCC5, and RPA1. In addition, WDR76 co-localizes to puncta with the heterochromatin proteins CBX1 and CBX5, which are also recruited to DNA damage but much less intensely than WDR76. This work demonstrates the chromatin and DNA damage protein associations of WDR76 and demonstrates the rapid response of WDR76 to laser induced DNA damage. PMID- 27248497 TI - Development of a PCR-Based Reverse Genetics System for an Attenuated Duck Tembusu Virus Strain. AB - The infectious disease caused by the duck Tembusu virus (DTMUV) has resulted in massive economic losses to the Chinese duck industry in China since 2010. Research on the molecular basis of DTMUV pathogenicity has been hampered by the lack of a reliable reverse genetics system for this virus. Here we developed a PCR-based reverse genetics system with high fidelity for the attenuated DTMUV strain FX2010-180P. The rescued virus was characterized by using both indirect immunofluorescence assays (IFA) and whole genome sequencing. The rescued virus (rFX2010-180P) grew to similar titers as compared with the wild-type virus in DF 1 cells, and had similar replication and immunogenicity properties in ducks. To determine whether exogenous proteins could be expressed from DTMUV, both an internal ribosomal entry site (IRES) and the enhanced green fluorescent protein (eGFP) gene were introduced between the NS5 gene and the 3' non-coding sequence of FX2010-180P. A recombinant DTMUV expressing eGFP was rescued, but eGFP expression was unstable after 4 passages in DF-1 cells due to a deletion of 1,294 nucleotides. The establishment of a reliable reverse genetics system for FX2010 180P provides a foundation for future studies of DTMUV. PMID- 27248498 TI - Regulation of G0/G1 Switch Gene 2 (G0S2) Protein Ubiquitination and Stability by Triglyceride Accumulation and ATGL Interaction. AB - Intracellular triglyceride (TG) hydrolysis or lipolysis is catalyzed by the key intracellular triglyceride hydrolase, adipose triglyceride lipase (ATGL). The G0/G1 Switch Gene 2 (G0S2) was recently identified as the major selective inhibitor of ATGL and its hydrolase function. Since G0S2 levels are dynamically linked and rapidly responsive to nutrient status or metabolic requirements, the identification of its regulation at the protein level is of significant value. Earlier evidence from our laboratory demonstrated that G0S2 is a short-lived protein degraded through the proteasomal pathway. However, little is currently known regarding the underlying mechanisms. In the current study we find that 1) protein degradation is initiated by K48-linked polyubiquitination of the lysine- 25 in G0S2; and 2) G0S2 protein is stabilized in response to ATGL expression and TG accumulation. Mutation of lysine-25 of G0S2 abolished ubiquitination and increased protein stability. More importantly, G0S2 was stabilized via different mechanisms in the presence of ATGL vs. in response to fatty acid (FA)-induced TG accumulation. Furthermore, G0S2 protein but not mRNA levels were reduced in the adipose tissue of ATGL-deficient mice, corroborating the involvement of ATGL in the stabilization of G0S2. Taken together our data illustrate for the first time a crucial multifaceted mechanism for the stabilization of G0S2 at the protein level. PMID- 27248499 TI - Intragenic Locus in Human PIWIL2 Gene Shares Promoter and Enhancer Functions. AB - Recently, more evidence supporting common nature of promoters and enhancers has been accumulated. In this work, we present data on chromatin modifications and non-polyadenylated transcription characteristic for enhancers as well as results of in vitro luciferase reporter assays suggesting that PIWIL2 alternative promoter in exon 7 also functions as an enhancer for gene PHYHIP located 60Kb upstream. This finding of an intragenic enhancer serving as a promoter for a shorter protein isoform implies broader impact on understanding enhancer-promoter networks in regulation of gene expression. PMID- 27248500 TI - Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, protects the pancreas from apoptosis and proliferation via oxidative stress in streptozotocin-induced diabetic rats. AB - We have identified the effects of oligonol, a low-molecular polyphenol derived from lychee fruit, on diabetes-induced pancreatic damage via oxidative stress. Oligonol was orally administered at 10 or 20 mg (kg d)(-1) for 10 days to streptozotocin (STZ)-induced diabetic rats, and we assessed the changes in the serum glucose and insulin levels, as well as those of body weight and food and water consumption. In addition, analyses of the weight, insulin content, reactive oxygen species (ROS) level, and western blots of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4 (Nox-4), p22(phox), p47(phox), phosphor c-Jun N-terminal kinase (p-JNK), Bax, cytochrome c, caspase 3, pancreatic duodenal homeobox (PDX-1) and cyclin E were also performed in the pancreas. However, these unfavorable outcomes under diabetes were reversed by oligonol administration. Oligonol treatment led to significantly attenuated histological damage in the pancreas. In conclusion, this study suggests that oligonol protects the pancreas from Bax and PDX-1 via oxidative stress for the prevention or delaying of diabetes mellitus. PMID- 27248501 TI - Use of essential gene, encoding prophobilinogen deaminase from extreme psychrophilic Colwellia sp. C1, to generate temperature-sensitive strain of Francisella novicida. AB - Previously, several essential genes from psychrophilic bacteria have been substituted for their homologues in mesophilic bacterial pathogens to make the latter temperature sensitive. It has been noted that an essential ligA gene from an extreme psychrophile, Colwellia sp. C1, yielded a gene product that is inactivated at 27 degrees C, the lowest that has been observed for any psychrophilic enzyme, and hypothesized that other essential proteins of that strain would also have low inactivation temperatures. This work describes the partial sequencing of the genome of Colwellia sp. C1 strain and the identification of 24 open reading frames encoding homologues of highly conserved bacterial essential genes. The gene encoding porphobilinogen deaminase (hemC), which is involved in the pathway of haem synthesis, has been tested for its ability to convert Francisella novicida into a temperature-sensitive strain. The hybrid strain carrying the C1-derived hemC gene exhibited a temperature-sensitive phenotype with a restrictive temperature of 36 degrees C. These results support the conclusion that Colwellia sp. C1 is a rich source of heat-labile enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: The issue of biosafety is often raised when it comes to work with pathogenic organisms. The main concern is caused by the risk of researchers being exposed to infectious doses of dangerous microbes. This paper analyses essential genes identified in partial genomic sequence of the psychrophilic bacterium Collwelia sp. C1. These sequences can be used as a mean of generating temperature-sensitive strains of pathogenic bacteria. Such strains are incapable of surviving at the temperature of human body. This means they could be applied as vaccines or for safer work with dangerous organisms. PMID- 27248502 TI - Cryoprecipitate AHF vs. fibrinogen concentrates for fibrinogen replacement in acquired bleeding patients - an economic evaluation. AB - BACKGROUND: Fibrinogen repletion in patients with acquired bleeding disorders can be accomplished by transfusing cryoprecipitate AHF (cryo) or fibrinogen concentrate (FC); thus, we undertook an economic evaluation from the transfusion service perspective regarding the use of cryo vs. FC in patients with acquired bleeding. METHODS: We created a model comparing the cost of cryo vs. FC from the transfusion service perspective. A patient with acquired bleeding requiring fibrinogen replacement could receive either 15-20 cryo units or 3-4 g FC, consistent with the guidelines from the European Task Force for Advanced Bleeding Care in Trauma. All model parameters were estimated from institutional experiences and the medical literature. Additionally, a survey of US Transfusion Medicine fellowship directors was conducted. RESULTS: After adjusting for 28% wastage and technologist salary, cryo cost is $414/5-unit pool. Depending on the dose, FC is more expensive by $976-$1303. To be competitive with cryo, FC cost must decrease by 44% or be shown to save 0.25-0.66 ICU days. Of the 30 survey replies, 96.7% of US centres do not use FC for acquired bleeding with the top three reasons being cost (30%), off-label usage (27%) and insufficient evidence for usage (20%). Only 47% are willing to pay more for FC, with $437/g as the median amount. CONCLUSION: Fibrinogen concentrate is more expensive than cryo, even after adjusting for cryo wastage. To be economically competitive with cryo, FC must cost $414/g, or save on ICU length of stay, consistent with the survey's results. PMID- 27248503 TI - Letter to the Editor: Author Response. PMID- 27248504 TI - Commentary on the diagnostic utility of non-invasive imaging devices for field cancerization. PMID- 27248506 TI - Sacrificing the buccal branch of the facial nerve during parotidectomy. AB - BACKGROUND: The need for and consequence of sacrificing the buccal branch of the facial nerve during parotidectomy is unknown. We sought to determine the indication, frequency, and functional outcome of buccal branch sacrifice. METHODS: We conducted a prospective study of all cases of parotidectomy at a tertiary referral center. RESULTS: Of 100 consecutive cases of parotidectomy, the buccal branch was sacrificed in 23 cases. This subgroup was more likely to have anterior or deep lesions (p < .001), retrograde facial nerve dissection (p = .037), and immediate postoperative upper and lower facial weakness (p = .051 and .002, respectively). However, if the temporozygomatic and cervicomandibular branches were anatomically preserved, full facial (including buccal) function was restored. CONCLUSION: Deep or anterior lesions may warrant sacrifice of the buccal branch for adequate access and excision. However, this does not result in long-term impairment of facial function. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1821-1825, 2016. PMID- 27248505 TI - In vivo modulation of endothelial polarization by Apelin receptor signalling. AB - Endothelial cells (ECs) respond to shear stress by aligning in the direction of flow. However, how ECs respond to flow in complex in vivo environments is less clear. Here we describe an endothelial-specific transgenic zebrafish line, whereby the Golgi apparatus is labelled to allow for in vivo analysis of endothelial polarization. We find that most ECs polarize within 4.5 h after the onset of vigorous blood flow and, by manipulating cardiac function, observe that flow-induced EC polarization is a dynamic and reversible process. Based on its role in EC migration, we analyse the role of Apelin signalling in EC polarization and find that it is critical for this process. Knocking down Apelin receptor function in human primary ECs also affects their polarization. Our study provides new tools to analyse the mechanisms of EC polarization in vivo and reveals an important role in this process for a signalling pathway implicated in cardiovascular disease. PMID- 27248507 TI - Patient awareness and beliefs about the risk factors and comorbidities associated with chronic kidney disease : A mixed-methods study. AB - AIM: Diabetes, hypertension and smoking may contribute to the development and progression of chronic kidney disease (CKD) and its complications. The aim of this study was to assess patients' awareness and beliefs about these and other risk factors associated with CKD. METHODS: Participants with CKD Stages 1-5 were purposively sampled for participation in a mixed methods study. Focus group participants completed a survey on CKD risk factors and discussed the reasons for their choices. Thematic analysis was used to analyse the qualitative data. RESULTS: Of the 38 participants, the proportion who identified hypertension, family history, diabetes and obesity as risk factors for CKD were 89%, 87%, 87% and 70% respectively. Only 54% and 38% recognized that smoking and Aboriginal or Torres Strait Islander status were risk factors. Participants considered the risks of heart attack, stroke and premature mortality to be 20-40% lower in people with CKD than those with diabetes or pre-existing cardiovascular disease. Five themes were identified: invisibility (lack of signs and symptoms of CKD), invincibility (participants did not feel they were at risk), lacking awareness (identified not knowing much about their disease), cumulative comorbidities (concerned about the increased risks of associated diseases) and inevitability of death (there is no cure for CKD). CONCLUSION: Participants had good understanding of some risk factors for CKD (hypertension and diabetes) but limited understanding of others. Awareness of comorbidities was also less than for other chronic conditions. Compared with diabetes and cardiovascular disease, CKD was perceived to pose less of a threat to life. Patient education that addresses CKD risk factors, comorbidities and outcomes may increase awareness and foster better self-management for people with CKD. PMID- 27248508 TI - Hepatitis B, C, and D virus infection showing distinct patterns between injection drug users and the general population. AB - BACKGROUND AND AIM: Hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are known to be prevalent in injection drug users (IDUs); however, the relationship between the molecular epidemiologic features of hepatitis virus infection in high-risk individuals and the general population has not yet been established. METHODS: In total, 1049 IDUs and 672 individuals who underwent physical examinations at Chenzhou hospital, Hunan Province, China, were enrolled. HBV, HCV, and HDV infections were screened with serologic tests in both populations. HBsAg-positive, anti-HCV IgG-positive, and anti-HDV IgG-positive samples were further confirmed by polymerase chain reaction, quantitative polymerase chain reaction, and DNA sequencing. RESULTS: Significantly higher HBV (21.54 vs 16.52%, P = 0.01), HCV (45.95% vs 1.34%, P < 0.001), and HDV (5.62% vs 0.30%, P < 0.001) infections were detected in IDUs compared with the general population. The dual infection of HBV/HCV or HBV/HDV was also significantly higher in IDUs than in the general population. HBV genotype B and HDV genotype II were dominants in both populations. HCV infection showed genotype 6a (49.52%) dominant in IDUs, but genotype 1b accounted for 50% infection, which was followed by genotype 6a (33.33%) in the general population. Higher viral loads were associated with HBV genotype B and HCV genotype 6a compared with non-dominant genotypic infections. CONCLUSIONS: HBV and HDV infections shared similar patterns by IDUs and the general populations, and HCV infection exhibited distinct features between two populations. Our results suggest different molecular epidemiologic characteristics of HBV, HCV, and HDV infection in two populations. PMID- 27248509 TI - A Review of the Internal and External Physiological Demands Associated With Batting in Cricket. AB - Cricket is a popular international team sport with various game formats ranging from long-duration multiday tests to short-duration Twenty20 game play. The role of batsmen is critical to all game formats, with differing physiological demands imposed during each format. Investigation of the physiological demands imposed during cricket batting has historically been neglected, with much of the research focusing on bowling responses and batting technique. A greater understanding of the physiological demands of the batting role in cricket is required to assist strength and conditioning professionals and coaches with the design of training plans, recovery protocols, and player-management strategies. This brief review provides an updated synthesis of the literature examining the internal (eg, metabolic demands and heart rate) and external (eg, activity work rates) physiological responses to batting in the various game formats, as well as simulated play and small-sided-games training. Although few studies have been done in this area, the summary of data provides important insight regarding physiological responses to batting and highlights that more research on this topic is required. Future research is recommended to combine internal and external measures during actual game play, as well as comparing different game formats and playing levels. In addition, understanding the relationship between batting technique and physiological responses is warranted to gain a more holistic understanding of batting in cricket, as well as to develop appropriate coaching and training strategies. PMID- 27248510 TI - Transition metal sulfides grown on graphene fibers for wearable asymmetric supercapacitors with high volumetric capacitance and high energy density. AB - Fiber shaped supercapacitors are promising candidates for wearable electronics because they are flexible and light-weight. However, a critical challenge of the widespread application of these energy storage devices is their low cell voltages and low energy densities, resulting in limited run-time of the electronics. Here, we demonstrate a 1.5 V high cell voltage and high volumetric energy density asymmetric fiber supercapacitor in aqueous electrolyte. The lightweight (0.24 g cm(-3)), highly conductive (39 S cm(-1)), and mechanically robust (221 MPa) graphene fibers were firstly fabricated and then coated by NiCo2S4 nanoparticles (GF/NiCo2S4) via the solvothermal deposition method. The GF/NiCo2S4 display high volumetric capacitance up to 388 F cm(-3) at 2 mV s(-1) in a three-electrode cell and 300 F cm(-3) at 175.7 mA cm(-3) (568 mF cm(-2) at 0.5 mA cm(-2)) in a two electrode cell. The electrochemical characterizations show 1000% higher capacitance of the GF/NiCo2S4 as compared to that of neat graphene fibers. The fabricated device achieves high energy density up to 12.3 mWh cm(-3) with a maximum power density of 1600 mW cm(-3), outperforming the thin-film lithium battery. Therefore, these supercapacitors are promising for the next generation flexible and wearable electronic devices. PMID- 27248511 TI - Simulation of Multi-Dimensional Signals in the Optical Domain: Quantum-Classical Feedback in Nonlinear Exciton Propagation. AB - We present an algorithm for the simulation of nonlinear 2D spectra of molecular systems in the UV-vis spectral region from atomistic molecular dynamics trajectories subject to nonadiabatic relaxation. We combine the nonlinear exciton propagation (NEP) protocol, that relies on a quasiparticle approach with the surface hopping methodology to account for quantum-classical feedback during the dynamics. Phenomena, such as dynamic Stokes shift due to nuclear relaxation, spectral diffusion, and population transfer among electronic states, are thus naturally included and benchmarked on a model of two electronic states coupled to a harmonic coordinate and a classical heatbath. The capabilities of the algorithm are further demonstrated for the bichromophore diphenylmethane that is described in a fully microscopic fashion including all 69 classical nuclear degrees of freedom. We demonstrate that simulated 2D signals are especially sensitive to the applied theoretical approximations (i.e., choice of active space in the CASSCF method) where population dynamics appears comparable. PMID- 27248512 TI - Stochastic Simulation of Biomolecular Networks in Dynamic Environments. AB - Simulation of biomolecular networks is now indispensable for studying biological systems, from small reaction networks to large ensembles of cells. Here we present a novel approach for stochastic simulation of networks embedded in the dynamic environment of the cell and its surroundings. We thus sample trajectories of the stochastic process described by the chemical master equation with time varying propensities. A comparative analysis shows that existing approaches can either fail dramatically, or else can impose impractical computational burdens due to numerical integration of reaction propensities, especially when cell ensembles are studied. Here we introduce the Extrande method which, given a simulated time course of dynamic network inputs, provides a conditionally exact and several orders-of-magnitude faster simulation solution. The new approach makes it feasible to demonstrate-using decision-making by a large population of quorum sensing bacteria-that robustness to fluctuations from upstream signaling places strong constraints on the design of networks determining cell fate. Our approach has the potential to significantly advance both understanding of molecular systems biology and design of synthetic circuits. PMID- 27248513 TI - Diverse genetic architectures lead to the same cryptic phenotype in a yeast cross. AB - Cryptic genetic variants that do not typically influence traits can interact epistatically with each other and mutations to cause unexpected phenotypes. To improve understanding of the genetic architectures and molecular mechanisms that underlie these interactions, we comprehensively dissected the genetic bases of 17 independent instances of the same cryptic colony phenotype in a yeast cross. In eight cases, the phenotype resulted from a genetic interaction between a de novo mutation and one or more cryptic variants. The number and identities of detected cryptic variants depended on the mutated gene. In the nine remaining cases, the phenotype arose without a de novo mutation due to two different classes of higher order genetic interactions that only involve cryptic variants. Our results may be relevant to other species and disease, as most of the mutations and cryptic variants identified in our study reside in components of a partially conserved and oncogenic signalling pathway. PMID- 27248514 TI - SMART: Statistical Metabolomics Analysis-An R Tool. AB - Metabolomics data provide unprecedented opportunities to decipher metabolic mechanisms by analyzing hundreds to thousands of metabolites. Data quality concerns and complex batch effects in metabolomics must be appropriately addressed through statistical analysis. This study developed an integrated analysis tool for metabolomics studies to streamline the complete analysis flow from initial data preprocessing to downstream association analysis. We developed Statistical Metabolomics Analysis-An R Tool (SMART), which can analyze input files with different formats, visually represent various types of data features, implement peak alignment and annotation, conduct quality control for samples and peaks, explore batch effects, and perform association analysis. A pharmacometabolomics study of antihypertensive medication was conducted and data were analyzed using SMART. Neuromedin N was identified as a metabolite significantly associated with angiotensin-converting-enzyme inhibitors in our metabolome-wide association analysis (p = 1.56 * 10(-4) in an analysis of covariance (ANCOVA) with an adjustment for unknown latent groups and p = 1.02 * 10(-4) in an ANCOVA with an adjustment for hidden substructures). This endogenous neuropeptide is highly related to neurotensin and neuromedin U, which are involved in blood pressure regulation and smooth muscle contraction. The SMART software, a user guide, and example data can be downloaded from http://www.stat.sinica.edu.tw/hsinchou/metabolomics/SMART.htm . PMID- 27248515 TI - Recurrence and Survival in Patients With Merkel Cell Carcinoma Undergoing Surgery Without Adjuvant Radiation Therapy to the Primary Site. AB - IMPORTANCE: The use of adjuvant radiation therapy (RT) to the primary site in Merkel cell carcinoma (MCC) is not uncommon. However, the need for adjuvant RT to the primary site in patients at low risk for local recurrence is questionable. OBJECTIVES: To examine the occurrence of true local, satellite, in-transit, regional, and distant recurrences in patients undergoing surgery alone without adjuvant RT to the primary site. To establish overall survival (OS), MCC-specific survival (MCCSS), and disease-free survival (DFS) relationships in a cohort of patients with MCC. DESIGN, SETTING, AND PARTICIPANTS: Our University of Michigan Multidisciplinary MCC Program database was used to obtain characteristics and outcome measures for 104 patients (105 primary MCCs) with tumors less than 2 cm in diameter. The majority of patients were treated between July 2006 and November 2012. MAIN OUTCOMES AND MEASURES: Outcome measures included the occurrence of true local, satellite, in-transit, regional, and distant recurrences. End points included OS, MCCSS, and DFS. RESULTS: Overall, information for 55 men and 49 women with 105 primary MCCs was obtained; 19 patients developed recurrent disease, and the mean time to first recurrence was 10.7 months. True local recurrence occurred in 1 patient with concurrent in-transit recurrence. Satellite recurrence occurred in 1 patient with concurrent regional recurrence. Four additional patients developed in-transit metastases. Thirteen patients had a regional recurrence component, 4 patients had distant metastases, and 6 patients developed subsequent regional and/or distant recurrences. Stratified by initial pathologic stage, the OS and MCCSS at 48 months were estimated to be 85.0% (95% CI, 71.8%-92.3%) and 94.4% (95% CI, 83.4%-98.2%) for patients with stage 1A/B disease and 63.2% (95% CI, 36.6%-81.1%) and 78.1% (95% CI, 50.0%-91.5%) for patients with stage 3A disease. The OS and MCCSS at 24 months for patients with stage 3B disease were both 50.0% (95% CI, 5.8%-84.5%). CONCLUSIONS AND RELEVANCE: In selected MCC patients with primary tumors less than 2 cm in diameter treated with surgery alone without adjuvant RT to the primary site, we found a low occurrence of true local recurrences and satellite recurrences. This relatively low rate of local recurrence questions the need for adjuvant RT to the primary tumor site in patients with small low-risk lesions. PMID- 27248516 TI - Prevalence of and disparities in HIV-related sexual risk behaviours among Chinese youth in relation to sexual orientation: a cross-sectional study. AB - Background: The aim of this study was to calculate the prevalence rate of HIV related sexual risk behaviours (HSRB) among Chinese youth and determine whether there was an association between sexual orientation and HSRB. Methods: This study used a nationally representative survey of youth aged 15-24 years in China. Population numbers, prevalence, and proportions were calculated where appropriate. chi2 tests were used to determine the difference within categorical variables. Multivariate logistic regression was used to calculate the adjusted odd ratios (AOR) and 95% confidence interval (CI). Results: The rate of any HSRB among sexually active youth was 79.43%, and the most common HSRB was lack of condom use during the first sexual experience (66.02%). After adjusting for demographic and socioeconomic variables (sex, age, residence, living with parents or not, father's education and annual family income), non-heterosexual orientation was found to significantly increase the odds of HSRB (AOR = 2.42, 95% CI: 1.16-5.05). Conclusions: Non-heterosexual youth are at a higher risk of partaking in HSRB. The high prevalence of HSRB indicates the insufficiency of sex education for Chinese youth, especially for non-heterosexual youth. Greater efforts should be made to increase reproductive and sexual health services for Chinese youth. PMID- 27248517 TI - Identifying genetic loci affecting antidepressant drug response in depression using drug-gene interaction models. AB - Antidepressants are often only moderately successful in decreasing the severity of depressive symptoms. In part, antidepressant treatment response in patients with depression is genetically determined. However, although a large number of studies have been conducted aiming to identify genetic variants associated with antidepressant drug response in depression, only a few variants have been repeatedly identified. Within the present review, we will discuss the methodological challenges and limitations of the studies that have been conducted on this topic to date (e.g., 'treated-only design', statistical power) and we will discuss how specifically drug-gene interaction models can be used to be better able to identify genetic variants associated with antidepressant drug response in depression. PMID- 27248518 TI - Controlled Substitution of Chlorine for Iodine in Single-Crystal Nanofibers of Mixed Perovskite MAPbI3- x Clx. AB - Longer carrier diffusion length and improved power conversion efficiency have been reported for thin-film solar cell of organolead mixed-halide perovskite MAPbI3- x Cl x in comparison with MAPbI3 . Instead of substituting I in the MAPbI3 lattice, Cl-incorporation has been shown to mainly improve the film morphology of perovskite absorber. Well-defined crystal structure, adjustable composition (x), and regular morphology, remains a formidable task. Herein, a facile solution-assembly method is reported for synthesizing single-crystalline nanofibers (NFs) of tetragonal-lattice MAPbI3- x Cl x with the Cl-content adjustable between 0 <= x <= 0.75, leading to a gradual blueshift of the absorption and photoluminescence maxima from x = 0 to 0.75. The photoresponsivity (R) of MAPbI3 NFs keeps almost unchanging at a value independent of the white light illumination intensity (P). In contrast, R of MAPbI3- x Cl x NFs decreases rapidly with increasing both the x and P values, indicating Cl-substitution increases the recombination traps of photogenerated free electrons and holes. This study provides a model system to examine the role of extrinsic Cl ions in both perovskite crystallography and optoelectronic properties. PMID- 27248519 TI - Corrigendum. PMID- 27248520 TI - Influence of pi-Iodide Intermolecular Interactions on Electronic Properties of Tin(IV) Iodide Semiconducting Complexes. AB - Coordination compounds with a tin center surrounded by both organic and inorganic ligands ([SnI4{(C6H5)3PO}2], [SnI4{(C6H5)2SO}2], and [SnI4(C5H5NO)2]) acting as molecular semiconductors are in the spotlight of this article. This is a new class of hybrid semiconducting materials where optoelectronic properties of inorganic core (SnI4) were tuned by organic ligands. The valence band is located at the inorganic portion of the molecule while the conduction band is made of carbon-based orbitals. This suggests the great importance of hydrogen bonds where iodine atoms play the role of an acceptor. Weak intermolecular interactions between iodine atoms and aromatic rings are essential in a band structure formation. These materials form orange-red crystals soluble in most of organic solvents. Their semiconducting properties are addressed experimentally via photovoltage measurements, as well as theoretically, using DFT and semiempirical approaches. PMID- 27248521 TI - Assessment of skeletal age on the basis of DXA-derived hand scans in elite youth soccer. AB - Physical performance is highly dependent on maturity. Therefore, consideration of maturity is recommended in the talent identification process. To date, skeletal age (SA) is assessed using X-ray scans. However, X-rays are associated with a 10 fold higher radiation compared to dual-energy X-ray absorptiometry (DXA). The aim of the study was to validate SA assessments in male soccer players with the DXA technique. Paired X-ray and DXA scans of the left hand of 63 Swiss U-15 national soccer players were performed. SA assessments were performed twice by two blinded raters using Tanner and Whitehouse' reference technique. Intrarater and interrater reliability as well as agreement between both techniques were tested. Intrarater and interrater reliabilities were excellent. Bland-Altman plots showed that SA assessments between X-ray and DXA differed by -0.2 years and 95% limits of agreement were +/-0.6 years. Therefore, DXA offered a replicable method for assessing SA and maturity in youth soccer players. PMID- 27248565 TI - When past is present: Substitutions of long-term memory for sensory evidence in perceptual judgments. AB - When perception is underdetermined by current sensory inputs, memories for related experiences in the past might fill in missing detail. To evaluate this possibility, we measured the likelihood of relying on long-term memory versus sensory evidence when judging the appearance of an object near the threshold of awareness. Specifically, we associated colors with shapes in long-term memory and then presented the shapes again later in unrelated colors and had observers judge the appearance of the new colors. We found that responses were well characterized as a bimodal mixture of original and current-color representations (vs. an integrated unimodal representation). That is, although irrelevant to judgments of the current color, observers occasionally anchored their responses on the original colors in memory. Moreover, the likelihood of such memory substitutions increased when sensory input was degraded. In fact, they occurred even in the absence of sensory input when observers falsely reported having seen something. Thus, although perceptual judgments intuitively seem to reflect the current state of the environment, they can also unknowingly be dictated by past experiences. PMID- 27248566 TI - The absolute disparity anomaly and the mechanism of relative disparities. AB - There has been a long-standing debate about the mechanisms underlying the perception of stereoscopic depth and the computation of the relative disparities that it relies on. Relative disparities between visual objects could be computed in two ways: (a) using the difference in the object's absolute disparities (Hypothesis 1) or (b) using relative disparities based on the differences in the monocular separations between objects (Hypothesis 2). To differentiate between these hypotheses, we measured stereoscopic discrimination thresholds for lines with different absolute and relative disparities. Participants were asked to judge the depth of two lines presented at the same distance from the fixation plane (absolute disparity) or the depth between two lines presented at different distances (relative disparity). We used a single stimulus method involving a unique memory component for both conditions, and no extraneous references were available. We also measured vergence noise using Nonius lines. Stereo thresholds were substantially worse for absolute disparities than for relative disparities, and the difference could not be explained by vergence noise. We attribute this difference to an absence of conscious readout of absolute disparities, termed the absolute disparity anomaly. We further show that the pattern of correlations between vergence noise and absolute and relative disparity acuities can be explained jointly by the existence of the absolute disparity anomaly and by the assumption that relative disparity information is computed from absolute disparities (Hypothesis 1). PMID- 27248567 TI - Corrections to: The spatiotemporal characteristics of the attentional shift relative to a reach. PMID- 27248568 TI - Husbandry and Health Program Survey Synopsis. PMID- 27248569 TI - Event DAS-444O6-6 soybean grown in Brazil is compositionally equivalent to non transgenic soybean. AB - Soybean event DAS-444O6-6 is tolerant to the herbicides 2,4-D, glyphosate, and glufosinate. An investigation of potential unintended adverse compositional changes in a genetically modified crop is required to meet government regulatory requirements in various geographies. A study to meet these requirements in Brazil was completed demonstrating compositional equivalency between DAS-444O6-6 and non transgenic soybean. This study supplements the extensive literature supporting transgenesis as less disruptive of crop composition compared with traditional breeding methods. PMID- 27248571 TI - Presacral Myelolipoma: Diagnosis on Imaging With Pathologic and Clinical Correlation. AB - OBJECTIVE: Myelolipoma is a benign tumor composed of fatty and hematopoietic elements. Presacral myelolipoma is rare, with fewer than 40 cases reported in the English literature. It is important to make an accurate diagnosis because there are malignant diseases included in the differential diagnosis of a presacral fatty mass, particularly liposarcoma. CONCLUSION: The combination of a well encapsulated fat-containing presacral mass, lack of coinciding hematologic disease, and uptake on sulfur colloid scintigraphy support the diagnosis of a presacral myelolipoma. PMID- 27248570 TI - Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR. AB - Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRDeltaE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRDeltaE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRDeltaE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker. PMID- 27248572 TI - Bariatric Surgery for Patients With Early-Onset vs Late-Onset Type 2 Diabetes. AB - IMPORTANCE: The prevalence of early-onset type 2 diabetes mellitus (T2DM), which responds poorly to medical treatment, is increasing. Bariatric surgery has been well recognized for its effectiveness in the remission of T2DM, but its effectiveness and durability in the remission of early-onset T2DM has not yet been explored. OBJECTIVE: To compare the short- and long-term outcomes of bariatric surgery with a specific focus on the rate of remission of T2DM in patients with early-onset (age <40 years) and late-onset (age >=40 years) T2DM. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, 558 Taiwanese patients (339 with early-onset T2DM and 219 with late-onset T2DM) with a body mass index (calculated as weight in kilograms divided by height in meters squared) above 25 underwent bariatric surgery to ameliorate T2DM between January 1, 2007, and December 31, 2013. Patients were followed up for at least 1 year. Preoperative, perioperative, and postoperative clinical and laboratory data were prospectively collected and compared between the 2 groups. MAIN OUTCOMES AND MEASURES: Rate of remission of T2DM (hemoglobin A1C <6.0% without antiglycemic medication) was the primary outcome measure. RESULTS: Of the 558 patients (345 women) in the study, mean (SD) ages were 33.5 (7.5) for those with early-onset T2DM and 50.6 (6.5) with late onset T2DM. Those with early-onset T2DM had higher mean (SD) preoperative BMI and hemoglobin A1C values (39.4 [8.5] and 8.7% [3.8%] of total hemoglobin [to convert hemoglobin to a proportion of total hemoglobin, multiply by 0.01], respectively) than did patients with late-onset T2DM (36.7 [7.5] and 8.2% [1.6%], respectively). Distribution of surgical procedures and major complications were similar between the 2 groups. At 1 year, patients with early onset T2DM achieved greater weight loss than those with late-onset T2DM, although the difference was not statistically significant. A higher rate of complete remission of T2DM was observed in patients with early-onset T2DM than in those with late-onset disease (193 [56.9%] vs 110 [50.2%]; P = .02). At 5 years, patients with early-onset T2DM still maintained a higher rate of weight loss (mean [SD], 30.4% [11.8%] vs 21.6% [11.7%]; P = .002) and higher rate of remission (47 of 72 [65.3%] vs 26 of 48 [54.2%]; P = .04) than did those with late-onset disease. Age at bariatric surgery, duration of T2DM, and preoperative C-peptide level were independent predictors of remission. The remission rate was directly related to extent of weight loss. Multivariate analysis confirmed the higher rate of remission in the group with early-onset T2DM. CONCLUSIONS AND RELEVANCE: This article describes the largest long-term study examining bariatric surgery for patients with early-onset T2DM. Bariatric surgery may achieve better and more long-lasting glycemic control in select patients with early-onset T2DM than in those with late-onset T2DM. PMID- 27248573 TI - Altering Antibody-Drug Conjugate Binding to the Neonatal Fc Receptor Impacts Efficacy and Tolerability. AB - Antibody-drug conjugates (ADC) rely on the target-binding specificity of an antibody to selectively deliver potent drugs to cancer cells. IgG antibody half life is regulated by neonatal Fc receptor (FcRn) binding. Histidine 435 of human IgG was mutated to alanine (H435A) to explore the effect of FcRn binding on the pharmacokinetics, efficacy, and tolerability of two separate maytansine-based ADC pairs with noncleavable linkers, (c-DM1 and c-H435A-DM1) and (7v-Cys-may and 7v H435A-Cys-may). The in vitro cell-killing potency of each pair of ADCs was similar, demonstrating that H435A showed no measurable impact on ADC bioactivity. The H435A mutant antibodies showed no detectable binding to human or mouse FcRn in vitro, whereas their counterpart wild-type IgG ADCs were found to bind to FcRn at pH = 6.0. In xenograft bearing SCID mice expressing mouse FcRn, the AUC of 7v Cys-may was 1.6-fold higher than that of 7v-H435A-may, yet the observed efficacy was similar. More severe thrombocytopenia was observed with 7v-H435A-Cys-may as compared to 7v-Cys-may at multiple dose levels. The AUC of c-DM1 was approximately 3-fold higher than that of c-H435A-DM1 in 786-0 xenograft bearing SCID mice, which led to a 3-fold difference in efficacy by dose. Murine FcRn knockout, human FcRn transgenic line 32 SCID animals bearing 786-0 xenografts showed an amplified exposure difference between c-DM1 and c-H435A-DM1 as compared to murine FcRn expressing SCID mice, leading to a 10-fold higher dose required for efficacy despite a 6-fold higher AUC of the c-H435A-DM1. The accelerated clearance observed for the noncleavable maytansine ADCs with the H435A FcRn mutation led to reduced efficacy at equivalent doses and exacerbation of clinical pathology parameters (decreased tolerability) at equivalent doses. The results show that reduced ADC clearance mediated by FcRn modulation can improve therapeutic index. PMID- 27248574 TI - New Home, New Prognosis? Reduced Hypertension Risk after Moving to a High Walkability Neighborhood. PMID- 27248575 TI - Global analysis of cellular protein flux quantifies the selectivity of basal autophagy. AB - In eukaryotic cells, the macroautophagy pathway has been implicated in the degradation of long-lived proteins and damaged organelles. Although it has been demonstrated that macroautophagy can selectively degrade specific targets, its contribution to the basal turnover of cellular proteins had previously not been quantified on proteome-wide scales. In a recent study, we utilized dynamic proteomics to provide a global comparison of protein half-lives between wild-type and autophagy-deficient cells. Our results indicated that in quiescent fibroblasts, macroautophagy contributes to the basal turnover of a substantial fraction of the proteome. However, the contribution of macroautophagy to constitutive protein turnover is variable within the proteome. The methodology outlined in the study provides a global strategy for quantifying the selectivity of basal macroautophagy. PMID- 27248576 TI - Widespread occurrence of perchlorate in water, foodstuffs and human urine collected from Kuwait and its contribution to human exposure. AB - Perchlorate is a thyroid hormone-disrupting compound and is reported to occur widely in the environment. Little is known on human exposure to perchlorate in Kuwait. In this study, 218 water samples, 618 commonly consumed foodstuffs and 532 urine samples collected from Kuwait were analysed to assess the exposure of the Kuwaiti population to perchlorate. For the estimation of daily intake of perchlorate, food consumption rates were obtained from the National Nutrition Survey in the State of Kuwait (NNSSK). The results showed that leafy vegetables accounted for a major share of perchlorate exposure among the Kuwaiti population at 0.062 ug kg(-)(1) bw day(-)(1) (36.2%), followed by fruits at 0.026 ug kg( )(1) bw day(-)(1) (15.3%) and non-leafy vegetables at 0.017 ug kg(-)(1) bw day( )(1) (10.1%). The urinary perchlorate geometric mean (GM) concentrations ranged from 8.51 to 17.1 ug l(-)(1) for the five age groups, which were higher than those reported in other countries. The estimated urinary perchlorate exposure for the Kuwaiti general population was 0.42 ug kg(-)(1) bw day(-)(1), which was higher than that reported for the United States. The dietary intake of perchlorate for the Kuwaiti population ranged from 0.14 to 0.67 ug kg(-)(1) bw day(-)(1) for the five age groups, with a mean total daily intake of 0.17 ug kg( )(1) bw day(-)(1) for the general population. The highest estimated dietary mean daily intake of perchlorate (0.67 ug kg(-)(1) bw day(-)(1)) was found for children at 3-5 years. The estimated dietary perchlorate exposure in Kuwait is higher than the recommended mean reference dose (RfD) but lower than that of provisional maximum tolerable daily intake (PMTDI) set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). PMID- 27248577 TI - Mammalian Cell Tissue Culture Techniques. AB - Cultured tissues and cells are used extensively in physiological and pharmacological studies. In vitro cultures provide a means of examining cells and tissues without the complex interactions that would be present if the whole organism were studied. A number of special skills are required in order to preserve the structure, function, behavior, and biology of cells in culture. This unit describes the basic skills required to maintain and preserve cell cultures: maintaining aseptic technique, preparing media with the appropriate characteristics, passaging, freezing and storage, recovering frozen stocks, and counting viable cells. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248579 TI - Assays for Determination of Protein Concentration. AB - Biochemical analysis of proteins relies on accurate quantification of protein concentration. Detailed in this appendix are some commonly used methods for protein analysis, e.g., Lowry, Bradford, bicinchoninic acid (BCA), UV spectroscopic, and 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde (CBQCA) assays. The primary focus of this report is assay selection, emphasizing sample and buffer compatibility. The fundamentals of generating protein assay standard curves and of data processing are considered, as are high-throughput adaptations of the more commonly used protein assays. Also included is a rapid, inexpensive, and reliable BCA assay of total protein in SDS-PAGE sample buffer that is used for equal loading of SDS-PAGE gels. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248578 TI - Genetically Engineered Mouse Models of Pancreatic Cancer: The KPC Model (LSL Kras(G12D/+) ;LSL-Trp53(R172H/+) ;Pdx-1-Cre), Its Variants, and Their Application in Immuno-oncology Drug Discovery. AB - Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths in the United States. For patients with unresectable disease, treatment options are limited and lack curative potential. Preclinical mouse models of PDAC that recapitulate the biology of human pancreatic cancer offer an opportunity for the rational development of novel treatment approaches that may improve patient outcomes. With the recent success of immunotherapy for subsets of patients with solid malignancies, interest is mounting in the possible use of immunotherapy for the treatment of PDAC. Considered in this unit is the value of genetic mouse models for characterizing the immunobiology of PDAC and for investigating novel immunotherapeutics. Several variants of these models are described, all of which may be used in drug development and for providing information on unique aspects of disease biology and therapeutic responsiveness. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248580 TI - Electrophilic, Activation-Free Fluorogenic Reagent for Labeling Bioactive Amines. AB - Herein we report the preparation of BODIPY mesoionic acid fluorides through a short sequence involving an isocyanide multicomponent reaction as the key synthetic step. These novel BODIPY acid fluorides are water-stable electrophilic reagents that can be used for the fluorescent derivatization of amine-containing biomolecules using mild and activation-free reaction conditions. As a proof of principle, we have labeled the antifungal natamycin and generated a novel fluorogenic probe for imaging a variety of human and plant fungal pathogens, with excellent selectivity over bacterial cells. PMID- 27248581 TI - Comparative Raman study of Weyl semimetals TaAs, NbAs, TaP and NbP. AB - We report a comparative polarized Raman study of Weyl semimetals TaAs, NbAs, TaP and NbP. The evolution of the phonon frequencies with the sample composition allows us to determine experimentally which atoms are mainly involved for each vibration mode. Our results confirm previous first-principles calculations indicating that the A1, B1(2), E(2) and E(3) modes involve mainly the As(P) atoms, the B1(1) mode is mainly related to Ta(Nb) atoms, and the E(1) mode involves both kinds of atoms. By comparing the energy of the different modes, we establish that the B1(1), B1(2), E(2) and E(3) become harder with increasing chemical pressure. This behaviour differs from our observation on the A1 mode, which decreases in energy, in contrast to its behaviour under external pressure. PMID- 27248582 TI - Can Alveolar Macrophages Made from Stem Cells Achieve Functional Rescue of Lung Diseases? PMID- 27248583 TI - Could Protecting the Immunoproteasome Reduce Exacerbations in Chronic Obstructive Pulmonary Disease? PMID- 27248584 TI - Recognizing the Many Faces of Chronic Obstructive Pulmonary Disease. PMID- 27248585 TI - The Recruitability Paradox. PMID- 27248586 TI - Clarifying Sepsis Management. PMID- 27248587 TI - Nature versus Nurture: Does Genetic Ancestry Alter the Effect of Air Pollution in Children with Asthma? PMID- 27248589 TI - Don't Let (Dl)CO Be Misunderstood. PMID- 27248588 TI - Sarcoidosis and T-Helper Cells. Th1, Th17, or Th17.1? PMID- 27248590 TI - Activation Profile of Mycobacterium tuberculosis-Specific CD4(+) T Cells Reflects Disease Activity Irrespective of HIV Status. PMID- 27248591 TI - Improved Survival of Patients with Pulmonary Arterial Hypertension with BMPR2 Mutations in the Last Decade. PMID- 27248592 TI - Different Definitions of Lung Recruitment by Computed Tomography Scan. PMID- 27248593 TI - Reply: Different Definitions of Lung Recruitment by Computed Tomography Scan. PMID- 27248594 TI - Apneic Oxygenation Has Not Been Disproven. PMID- 27248595 TI - Reply: Apneic Oxygenation Has Not Been Disproven. PMID- 27248597 TI - Expression of Concern: Protection from Lipopolysaccharide-induced Lung Injury by Augmentation of Airway S-Nitrosothiols. PMID- 27248596 TI - Erratum: Sustained Benefit from Ivacaftor Demonstrated by Combining Clinical Trial and Cystic Fibrosis Patient Registry Data. PMID- 27248598 TI - Bronchiolitis Obliterans Syndrome (BOS) Following Lung Transplant. PMID- 27248613 TI - Thermodynamic-Driven Self-Assembly: Heterochiral Self-Sorting and Structural Reconfiguration in Gold(I)-Sulfido Cluster System. AB - By employing chiral precursors, a new class of chiral gold(I)-sulfido clusters with unique structures has been constructed. Interestingly, pure enantiomers of the precursors are found to self-assemble into chiral hexa- and decanuclear clusters sequentially, while a racemic mixture of them has resulted in heterochiral self-sorting of an achiral meso decanuclear cluster. Chirality has determined not only the symmetry and structures but also the photophysical behaviors of these clusters. The racemic mixture of decanuclear clusters undergoes rearrangement and heterochiral self-sorting to give a meso decanuclear cluster. The thermodynamic-driven heterochiral self-sorting of gold(I) clusters provides a means to develop controlled self-assembly that may be of relevance to the understanding of chirality in nature. PMID- 27248614 TI - Stepwise surgical approach to equinocavovarus in patients with cerebral palsy: Erratum. PMID- 27248616 TI - Reimbursing Wisely? CMS's Trial of Medicare Part B Drug Payment Reform. PMID- 27248615 TI - Descriptive analysis of the masticatory and salivary functions and gustatory sensitivity in healthy children. AB - OBJECTIVE: The objective of this study is to better understand salivary and masticatory characteristics, this study evaluated the relationship among salivary parameters, bite force (BF), masticatory performance (MP) and gustatory sensitivity in healthy children. The secondary outcome was to evaluate possible gender differences. MATERIALS AND METHODS: One hundred and sixteen eutrophic subjects aged 7-11 years old were evaluated, caries-free and with no definite need of orthodontic treatment. Salivary flow rate and pH, total protein (TP), alpha-amylase (AMY), calcium (CA) and phosphate (PHO) concentrations were determined in stimulated (SS) and unstimulated saliva (US). BF and MP were evaluated using digital gnathodynamometer and fractional sieving method, respectively. Gustatory sensitivity was determined by detecting the four primary tastes (sweet, salty, sour and bitter) in three different concentrations. Data were evaluated using descriptive statistics, Mann-Whitney/t-test, Spearman correlation and multiple regression analysis, considering alpha = 0.05. RESULTS: Significant positive correlation between taste and age was observed. CA and PHO concentrations correlated negatively with salivary flow and pH; sweet taste scores correlated with AMY concentrations and bitter taste sensitivity correlated with US flow rate (p < 0.05). No significant difference between genders in salivary, masticatory characteristics and gustatory sensitivity was observed. The regression analysis showed a weak relationship between the distribution of chewed particles among the different sieves and BF. CONCLUSIONS: The concentration of some analytes was influenced by salivary flow and pH. Age, saliva flow and AMY concentrations influenced gustatory sensitivity. In addition, salivary, masticatory and taste characteristics did not differ between genders, and only a weak relation between MP and BF was observed. PMID- 27248617 TI - The ACA and Risk Pools--Insurer Losses in the Setting of Noncompliant Plans. PMID- 27248618 TI - A Modern Ars Moriendi. PMID- 27248619 TI - A Program to Prevent Catheter-Associated Urinary Tract Infection in Acute Care. AB - BACKGROUND: Catheter-associated urinary tract infection (UTI) is a common device associated infection in hospitals. Both technical factors--appropriate catheter use, aseptic insertion, and proper maintenance--and socioadaptive factors, such as cultural and behavioral changes in hospital units, are important in preventing catheter-associated UTI. METHODS: The national Comprehensive Unit-based Safety Program, funded by the Agency for Healthcare Research and Quality, aimed to reduce catheter-associated UTI in intensive care units (ICUs) and non-ICUs. The main program features were dissemination of information to sponsor organizations and hospitals, data collection, and guidance on key technical and socioadaptive factors in the prevention of catheter-associated UTI. Data on catheter use and catheter-associated UTI rates were collected during three phases: baseline (3 months), implementation (2 months), and sustainability (12 months). Multilevel negative binomial models were used to assess changes in catheter use and catheter associated UTI rates. RESULTS: Data were obtained from 926 units (59.7% were non ICUs, and 40.3% were ICUs) in 603 hospitals in 32 states, the District of Columbia, and Puerto Rico. The unadjusted catheter-associated UTI rate decreased overall from 2.82 to 2.19 infections per 1000 catheter-days. In an adjusted analysis, catheter-associated UTI rates decreased from 2.40 to 2.05 infections per 1000 catheter-days (incidence rate ratio, 0.86; 95% confidence interval [CI], 0.76 to 0.96; P=0.009). Among non-ICUs, catheter use decreased from 20.1% to 18.8% (incidence rate ratio, 0.93; 95% CI, 0.90 to 0.96; P<0.001) and catheter associated UTI rates decreased from 2.28 to 1.54 infections per 1000 catheter days (incidence rate ratio, 0.68; 95% CI, 0.56 to 0.82; P<0.001). Catheter use and catheter-associated UTI rates were largely unchanged in ICUs. Tests for heterogeneity (ICU vs. non-ICU) were significant for catheter use (P=0.004) and catheter-associated UTI rates (P=0.001). CONCLUSIONS: A national prevention program appears to reduce catheter use and catheter-associated UTI rates in non ICUs. (Funded by the Agency for Healthcare Research and Quality.). PMID- 27248620 TI - Integrating Randomized Comparative Effectiveness Research with Patient Care. PMID- 27248621 TI - IMAGES IN CLINICAL MEDICINE. Gastrointestinal Complication of Granulomatosis with Polyangiitis. PMID- 27248624 TI - Catheter-Associated Urinary Tract Infections--Turning the Tide. PMID- 27248622 TI - CLINICAL PROBLEM-SOLVING. The Hidden Lesion. PMID- 27248625 TI - CLINICAL DECISIONS. E-Cigarettes and Smoking Cessation. PMID- 27248626 TI - Assessing the Gold Standard--Lessons from the History of RCTs. PMID- 27248627 TI - CDX2 as a Prognostic Biomarker in Colon Cancer. PMID- 27248628 TI - CDX2 as a Prognostic Biomarker in Colon Cancer. PMID- 27248629 TI - CDX2 as a Prognostic Biomarker in Colon Cancer. PMID- 27248630 TI - CDX2 as a Prognostic Biomarker in Colon Cancer. PMID- 27248631 TI - New Agents to Treat Chronic Lymphocytic Leukemia. PMID- 27248632 TI - New Agents to Treat Chronic Lymphocytic Leukemia. PMID- 27248633 TI - New Agents to Treat Chronic Lymphocytic Leukemia. PMID- 27248634 TI - Therapy for Tuberculous Meningitis. PMID- 27248635 TI - Therapy for Tuberculous Meningitis. PMID- 27248636 TI - Therapy for Tuberculous Meningitis. PMID- 27248637 TI - Therapy for Tuberculous Meningitis. PMID- 27248638 TI - Planned Out-of-Hospital Birth and Birth Outcomes. PMID- 27248639 TI - Planned Out-of-Hospital Birth and Birth Outcomes. PMID- 27248640 TI - Planned Out-of-Hospital Birth and Birth Outcomes. PMID- 27248641 TI - Urinary Tract Infections in Older Men. PMID- 27248642 TI - Urinary Tract Infections in Older Men. PMID- 27248643 TI - Urinary Tract Infections in Older Men. PMID- 27248644 TI - Case 41-2015: A Boy with Immune and Liver Abnormalities. PMID- 27248645 TI - Case 41-2015: A Boy with Immune and Liver Abnormalities. PMID- 27248646 TI - IMAGES IN CLINICAL MEDICINE. Intrafacial Synkinesis. PMID- 27248647 TI - Cox-maze IV cryoablation and postoperative heart failure in mitral valve surgery patients. AB - OBJECTIVE: The indications for and the risk and benefit of concomitant surgical ablation for atrial fibrillation (AF) have not been fully delineated. Our aim was to survey whether the Cox-maze IV procedure is associated with postoperative heart failure (PHF) or other adverse short-term outcomes after mitral valve surgery (MVS). DESIGN: Consecutive patients with AF undergoing MVS with (n = 50) or without (n = 66) concomitant Cox-maze IV cryoablation were analysed regarding perioperative data and one-year mortality. RESULTS: The patients in the Maze group were younger, were in lower NYHA classes, had better right ventricular function and had lower pulmonary artery pressure. The Maze group had 30 min longer median cross-clamp time (CCT) and 50% had PHF compared with 33% in the No maze group, p = 0.09. Two patients in the No-maze group died within one year of surgery. Congestive heart failure (OR 4.3 [CI 95%: 1.8-10], p < 0.0001) and CCT (OR 1.03 [CI 95%: 1.01-1.04], p = 0.001) were associated with PHF. CONCLUSION: The current data cannot exclude that concomitant cryoablation increases the risk for PHF, possibly by increasing the cross clamp time. PMID- 27248648 TI - Psychological masochism: A systematic review of the literature on conflicts, defenses, and motives. AB - OBJECTIVE: Our aim was to conduct a systematic review of the literature on psychological masochism to identify hypotheses for examination in clinical studies. METHOD: We identified defenses, conflicts, and motives using standardized measures in 23 psychoanalytic papers. RESULTS: Three primary and three secondary subtypes of masochism emerged in the literature. Overall Gratification Inhibition (subtype I.1) was the "healthiest" form, associated with higher developmental level motives and neurotic defenses. The Global Conflict (I.2) was the least healthy form of masochism, consistent with personality disorder. It was associated with early developmental level motives and immature defenses, including depressive defenses, often associated with depression. Dominant Other (I.3) represented masochistic attachment problems, associated with early developmental level motives, object-related, image-distorting defenses, and narcissism. Of the secondary types, Separation-Abandonment (II.1) reflected object-related defenses, and separation-related motives. Rejection of Others (II.2) represented a sadistic-narcissistic form, associated with image-distorting and disavowal defenses, with both early and later developmental level motives. Finally, Sexual Pleasure vs. Guilt (II.3) was associated with autistic fantasy, and both early and later developmental level motives, suggesting a distinct traumatic origin and representing the juncture of sexual and psychological masochism. CONCLUSIONS: Analysts described six distinguishable types of masochism. Future studies should examine their validity. PMID- 27248649 TI - Transarterial Alcohol-Lipiodol Therapy in Patients with Hepatocellular Carcinoma Using Low Alcohol Concentrations. AB - PURPOSE: To evaluate transarterial alcohol-lipiodol therapy (TAL) with low concentrations of alcohol for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 17 patients (69.3 +/- 10.7a, 13 male, 4 female) with previously untreated HCC (tumor diameter: 7.7 +/- 5.8 cm), who underwent 20 transarterial alcohol-lipiodol injections, were evaluated retrospectively. 14 patients had HCC with coexistent cirrhosis (Child-A n = 9, Child-B n = 4, Child-C n = 1). 9 patients presented an Okuda stage I, 7 patients an Okuda stage II and 1 patient an Okuda stage III. Infiltration of the portal vein was seen in 3 patients. RESULTS: 15 patients underwent TAL with an alcohol:lipiodol ratio of 1:2, another one with a ratio of 1:3 and yet another one with a ratio of 1:5. The median survival was 23 months, and the 1-year and 2-year survival rates were 62.7 % and 31.4 %, respectively. The median survival of patients with HCC < 7.5 cm (n = 10) was 25 months and significantly (p = 0.009) higher than for patients with HCC >= 7.5 cm (n = 7; 3 months). Tumor diameters >= 7.5 cm were associated with worse lipiodol-contrasting of HCC. Intrainterventional side effects were only feelings of slight abdominal pressure in 2 of 20 interventions. Postinterventional, mild side effects were observed after 3 interventions (abdominal pain n = 1, thoracic pain n = 1, fever n = 1). Serious complications were not observed, in particular there was no decompensation of liver cirrhosis. CONCLUSION: TAL with low concentrations of alcohol was a safe and effective treatment in our cohort in spite of extensive tumors and impaired liver function. TAL could be a treatment option for patients who cannot receive other therapies (e. g. TACE, RFA) because of their advanced tumor disease, liver cirrhosis or other contraindications. KEY POINTS: * TAL can be performed safely in advanced tumor disease and liver cirrhosis Citation Format: * Mohne F, Meyer C, Kuhl CK et al. Transarterial Alcohol-Lipiodol Therapy in Patients with Hepatocellular Carcinoma Using Low Alcohol Concentrations. Fortschr Rontgenstr 2016; 188: 676 - 683. PMID- 27248650 TI - Radiation Protection Clothing in X-Ray Diagnostics - Influence of the Different Methods of Measurement on the Lead Equivalent and the Required Mass. AB - PURPOSE: The determination of attenuation compared to lead for lead-free and lead reduced protective clothing depends strongly on the different methods of measurement. The standards EN 61331-1 (2002), DIN 6857-1 und IEC 61331-1 (2014) are now available for the testing of protective clothing. These standards define methods in the narrow beam and in the inverse broad beam geometry with partially different radiation qualities. In the narrow beam the scattered radiation and fluorescence are not considered due to the arrangement. Therefore, the protective effect of lead-free materials will be incorrectly estimated compared to lead material. The influence of the different methods of measurement on the lead equivalent and the required mass of radiation protection clothing was examined. MATERIALS AND METHODS: The lead equivalents for material samples for commercially available protective clothing were determined. These samples were made of lead and lead-reduced and lead-free materials. For determination of the attenuation equivalents, certified lead foils with high purity and a precise thickness of 0.05 to 1.25 mm were used. RESULTS: The measurements indicate that the lead equivalent depends on the method of measurement and the radiation quality. For X ray tube voltages below 110 kV, lead-free or lead-reduced materials show a higher lead equivalent compared to lead material in some cases. Significant mass reductions of more than 10 % compared to lead material are only achievable with a limited range of use up to 100 kV. CONCLUSION: The implementation of an internationally accepted measuring standard for radiation protection clothing is reasonable and necessary. If standard IEC 61331-1 (2014) can fill this role is unknown. Key points * The attenuation factor and the lead equivalent depend strongly on the method of measurement.* The used X-ray spectra are only partially comparable with the spectra of scattered radiation.* Mass reductions for protective clothing are only achievable with a limited range of use. Citation Format: * Schopf T, Pichler T. Radiation Protection Clothing in X-Ray Diagnostics - Influence of the Different Methods of Measurement on the Lead Equivalent and the Required Mass. Fortschr Rontgenstr 2016; 188: 768 - 775. PMID- 27248651 TI - Superinfection of a Pericardial Hydatid Cyst Leading to Sepsis and Multi-Organ Failure. PMID- 27248652 TI - [Not Available]. PMID- 27248653 TI - [Not Available]. PMID- 27248654 TI - ESCRT-II controls retinal axon growth by regulating DCC receptor levels and local protein synthesis. AB - Endocytosis and local protein synthesis (LPS) act coordinately to mediate the chemotropic responses of axons, but the link between these two processes is poorly understood. The endosomal sorting complex required for transport (ESCRT) is a key regulator of cargo sorting in the endocytic pathway, and here we have investigated the role of ESCRT-II, a critical ESCRT component, in Xenopus retinal ganglion cell (RGC) axons. We show that ESCRT-II is present in RGC axonal growth cones (GCs) where it co-localizes with endocytic vesicle GTPases and, unexpectedly, with the Netrin-1 receptor, deleted in colorectal cancer (DCC). ESCRT-II knockdown (KD) decreases endocytosis and, strikingly, reduces DCC in GCs and leads to axon growth and guidance defects. ESCRT-II-depleted axons fail to turn in response to a Netrin-1 gradient in vitro and many axons fail to exit the eye in vivo These defects, similar to Netrin-1/DCC loss-of-function phenotypes, can be rescued in whole (in vitro) or in part (in vivo) by expressing DCC. In addition, ESCRT-II KD impairs LPS in GCs and live imaging reveals that ESCRT-II transports mRNAs in axons. Collectively, our results show that the ESCRT-II mediated endocytic pathway regulates both DCC and LPS in the axonal compartment and suggest that ESCRT-II aids gradient sensing in GCs by coupling endocytosis to LPS. PMID- 27248655 TI - EZH2 regulates neuroepithelium structure and neuroblast proliferation by repressing p21. AB - The function of EZH2 as a transcription repressor is well characterized. However, its role during vertebrate development is still poorly understood, particularly in neurogenesis. Here, we uncover the role of EZH2 in controlling the integrity of the neural tube and allowing proper progenitor proliferation. We demonstrate that knocking down the EZH2 in chick embryo neural tubes unexpectedly disrupts the neuroepithelium (NE) structure, correlating with alteration of the Rho pathway, and reduces neural progenitor proliferation. Moreover, we use transcriptional profiling and functional assays to show that EZH2-mediated repression of p21(WAF1/CIP1) contributes to both processes. Accordingly, overexpression of cytoplasmic p21(WAF1/CIP1) induces NE structural alterations and p21(WAF1/CIP1) suppression rescues proliferation defects and partially compensates for the structural alterations and the Rho activity. Overall, our findings describe a new role of EZH2 in controlling the NE integrity in the neural tube to allow proper progenitor proliferation. PMID- 27248656 TI - Hsp90beta is involved in the development of high salt-diet-induced nephropathy via interaction with various signalling proteins. AB - A high-salt diet often leads to a local intrarenal increase in renal hypoxia and oxidative stress, which are responsible for an excess production of pathogenic substances. Here, Wistar Kyoto/spontaneous hypertensive (WKY/SHR) rats fed a high salt diet developed severe proteinuria, resulting from pronounced renal inflammation, fibrosis and tubular epithelial cell apoptosis. All these were mainly non-pressure-related effects. Hsp90beta, TGF-beta, HIF-1alpha, TNF-alpha, IL-6 and MCP-1 were shown to be highly expressed in response to salt loading. Next, we found that Hsp90beta might play the key role in non-pressure-related effects of salt loading through a series of cellular signalling events, including the NF-kappaB, p38 activation and Bcl-2 inactivation. Hsp90beta was previously proven to regulate the upstream mediators in multiple cellular signalling cascades through stabilizing and maintaining their activities. In our study, 17 dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) or Hsp90beta knockdown dramatically alleviated the high-salt-diet-induced proteinuria and renal damage without altering blood pressure significantly, when it reversed activations of NF kappaB, mTOR and p38 signalling cascades. Meanwhile, Co-IP results demonstrated that Hsp90beta could interact with and stabilize TAK1, AMPKalpha, IKKalpha/beta, HIF-1alpha and Raptor, whereas Hsp90beta inhibition disrupted this process. In addition, Hsp90beta inhibition-mediated renal improvements also accompanied the reduction of renal oxidative stress. In conclusion, salt loading indeed exhibited non-pressure-related impacts on proteinuria and renal dysfunction in WKY/SHR rats. Hsp90beta inhibition caused the destabilization of upstream mediators in various pathogenic signalling events, thereby effectively ameliorating this nephropathy owing to renal hypoxia and oxidative stress. PMID- 27248658 TI - A 3.6 nm Ti52-Oxo Nanocluster with Precise Atomic Structure. AB - We report a 3.6 nm Ti52-oxo cluster with precise atomic structure, which presents a largest size record in the family of titanium-oxo clusters (TOCs). The crystal growth of such large Ti52 is based on a stepwise interlayer assembly approach from Ti6 substructures. The possible growth mechanism of Ti52 could be deduced from crystal structures of two substructures, Ti6 and Ti17, which were also synthesized under similar conditions as Ti52. Moreover, these TOCs show cluster size-dependent photocatalytic hydrogen evolution activities with Ti52 giving a H2 production rate up to 398 MUmol/h/g, which is also the highest record in the family of TOCs. This work not only represents a milestone in constructing large TOCs with comparable sizes as TiO2 nanoparticles but also brings significant advances in improving photocatalytic behaviors of TOCs. PMID- 27248657 TI - Constitutive translation of human alpha-synuclein is mediated by the 5' untranslated region. AB - Genetic and biochemical studies have established a central role for alpha synuclein (SNCA) accumulation in the pathogenesis of Parkinson's disease. Uncovering and subsequently interfering with physiological mechanisms that control SNCA expression is one approach to limit disease progression. To this end, the long and GC-rich 5'-untranslated region (UTR) of SNCA, which is predicted to fold into stable hairpin and G-quadruplex RNA motifs, was investigated for its role in mRNA translation. Inclusion of SNCA 5'-UTR significantly induced expression of both SNCA and luciferase ORF constructs. This effect was not associated with a change in mRNA levels or differential nucleocytoplasmic shuttling. Further, the presence of the 5'-UTR enhanced SNCA synthesis when cap-dependent translation was attenuated with rapamycin treatment. Analysis using multiple methodologies revealed that the 5'-UTR harbours an internal ribosome entry site (IRES) element that spans most of its nucleotide sequence. Signals such as plasma-membrane depolarization, serum starvation and oxidative stress stimulated SNCA protein translation via its 5'-UTR as well as enhanced its IRES activity. Taken together, these data support the idea that the 5'-UTR is an important positive regulator of SNCA synthesis under diverse physiological and pathological conditions, explaining in part the abundance of SNCA in healthy neurons and its accumulation in degenerative cells. PMID- 27248659 TI - Large-Scale Sublattice Asymmetry in Pure and Boron-Doped Graphene. AB - The implementation of future graphene-based electronics is essentially restricted by the absence of a band gap in the electronic structure of graphene. Options of how to create a band gap in a reproducible and processing compatible manner are very limited at the moment. A promising approach for the graphene band gap engineering is to introduce a large-scale sublattice asymmetry. Using photoelectron diffraction and spectroscopy we have demonstrated a selective incorporation of boron impurities into only one of the two graphene sublattices. We have shown that in the well-oriented graphene on the Co(0001) surface the carbon atoms occupy two nonequivalent positions with respect to the Co lattice, namely top and hollow sites. Boron impurities embedded into the graphene lattice preferably occupy the hollow sites due to a site-specific interaction with the Co pattern. Our theoretical calculations predict that such boron-doped graphene possesses a band gap that can be precisely controlled by the dopant concentration. B-graphene with doping asymmetry is, thus, a novel material, which is worth considering as a good candidate for electronic applications. PMID- 27248660 TI - Estimating and projecting the effect of cold waves on mortality in 209 US cities. AB - The frequency, duration, and intensity of cold waves are expected to decrease in the near future under the changing climate. However, there is a lack of understanding on future mortality related to cold waves. The present study conducted a large-scale national projection to estimate future mortality attributable to cold waves during 1960-2050 in 209 US cities. Cold waves were defined as two, three, or at least four consecutive days with daily temperature lower than the 5th percentile of temperatures in each city. The lingering period of a cold wave was defined as the non-cold wave days within seven days following that cold wave period. First, with 168million residents in 209 US cities during 1962-2006, we fitted over-dispersed Poisson regressions to estimate the immediate and lingering effects of cold waves on mortality and tested if the associations were modified by the duration of cold waves, the intensity of cold waves, and mean winter temperature (MWT). Then we projected future mortality related to cold waves using 20 downscaled climate models. Here we show that the cold waves (both immediate and lingering) were associated with an increased but small risk of mortality. The associations varied substantially across climate regions. The risk increased with the duration and intensity of cold waves but decreased with MWT. The projected mortality related to cold waves would decrease from 1960 to 2050. Such a decrease, however, is small and may not be able to offset the potential increase in heat-related deaths if the adaptation to heat is not adequate. PMID- 27248661 TI - Brominated flame retardants in the indoor environment - Comparative study of indoor contamination from three countries. AB - Concentrations of more than 20 brominated flame retardants (FRs), including polybrominated diphenyl ethers (PBDEs) and emerging FRs, were measured in air, dust and window wipes from 63 homes in Canada, the Czech Republic and the United States in the spring and summer of 2013. Among the PBDEs, the highest concentrations were generally BDE-209 in all three matrices, followed by Penta BDEs. Among alternative FRs, EHTBB and BEHTBP were detected at the highest concentrations. DBDPE was also a major alternative FR detected in dust and air. Bromobenzenes were detected at lower levels than PBDEs and other alternative FRs; among the bromobenzenes, HBB and PBEB were the most abundant compounds. In general, FR levels were highest in the US and lowest in the Czech Republic - a geographic trend that reflects the flame retardants' market. No statistically significant differences were detected between bedroom and living room FR concentrations in the same house (n=10), suggesting that sources of FRs are widespread indoors and mixing between rooms. The concentrations of FRs in air, dust, and window film were significantly correlated, especially for PBDEs. We found a significant relationship between the concentrations in dust and window film and in the gas phase for FRs with log KOA values <14, suggesting that equilibrium was reached for these but not compounds with log KOA values >14. This hypothesis was confirmed by a large discrepancy between values predicted using a partitioning model and the measured values for FRs with log KOA values >14. PMID- 27248662 TI - Sub-acute systemic erythropoietin administration reduces ischemic brain injury in an age-dependent manner. AB - Stroke is associated with neuroinflammation, neuronal loss and blood-brain barrier (BBB) breakdown. Thus far, recombinant tissue-type plasminogen activator (rtPA), the only approved treatment for acute ischemic stroke, increases the risk of intracerebral hemorrhage and is poorly efficient in disaggregating platelet rich thrombi. Therefore, the development of safer and more efficient therapies is highly awaited. Encouraging neuroprotective effects were reported in mouse models of ischemic stroke following administration of erythropoietin (EPO). However, previous preclinical studies did not investigate the effects of EPO in focal ischemic stroke induced by a platelet-rich thrombus and did not consider the implication of age. Here, we performed middle cerebral artery occlusion by inducing platelet-rich thrombus formation in chimeric 5- (i.e. young) and 20- (i.e. aged) months old C57BL/6 mice, in which hematopoietic stem cells carried the green fluorescent protein (GFP)-tag. Recombinant human EPO (rhEPO) was administered 24 hours post-occlusion and blood-circulating monocyte populations were studied by flow cytometry 3 hours post-rhEPO administration. Twenty-four hours following rhEPO treatment, neuronal loss and BBB integrity were assessed by quantification of Fluoro-Jade B (FJB)-positive cells and extravasated serum immunoglobulins G (IgG), respectively. Neuroinflammation was determined by quantifying infiltration of GFP-positive bone marrow-derived cells (BMDC) and recruitment of microglial cells into brain parenchyma, along with monocyte chemotactic protein-1 (MCP-1) brain protein levels. Here, rhEPO anti-inflammatory properties rescued ischemic injury by reducing neuronal loss and BBB breakdown in young animals, but not in aged littermates. Such age-dependent effects of rhEPO must therefore be taken into consideration in future studies aiming to develop new therapies for ischemic stroke. PMID- 27248663 TI - Targeting hypoxic microenvironment of pancreatic xenografts with the hypoxia activated prodrug TH-302. AB - Previous reports have suggested that the hypoxic microenvironment provides a niche that supports tumor stem cells, and that this might explain clinical observations linking hypoxia to metastasis. To test this, we examined the effects of a hypoxia-activated prodrug, TH-302, on the tumor-initiating cell (TIC) frequency of patient-derived pancreatic xenografts (PDX).The frequencies of TIC, measured by limiting dilution assay, varied widely in 11 PDX models, and were correlated with rapid growth but not with the levels of hypoxia. Treatment with either TH-302 or ionizing radiation (IR), to target hypoxic and well-oxygenated regions, respectively, reduced TIC frequency, and the combination of TH-302 and IR was much more effective in all models tested. The combination was also more effective than TH-302 or IR alone controlling tumor growth, particularly treating the more rapidly-growing/hypoxic models. These findings support the clinical utility of hypoxia targeting in combination with radiotherapy to treat pancreatic cancers, but do not provide strong evidence for a hypoxic stem cell niche. PMID- 27248664 TI - BO-1055, a novel DNA cross-linking agent with remarkable low myelotoxicity shows potent activity in sarcoma models. AB - DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; gamma-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO 1055 caused apoptosis and cell death in a concentration and time dependent manner in sarcoma cell lines. BO-1055 had potent activity (submicromolar IC50) against Ewing sarcoma and rhabdomyosarcoma, intermediate activity in DSRCT (IC50 = 2 3MUM) and very weak activity in osteosarcoma (IC50 >10MUM) cell lines. BO-1055 exhibited a wide therapeutic window compared to other DNA damaging drugs. BO-1055 induced more DNA double strand breaks and gammaH2AX expression in cancer cells compared to benign cells. BO-1055 showed inhibition of tumor growth in A673 xenografts and caused tumor regression in cyclophosphamide resistant patient derived Ewing sarcoma xenografts and A204 xenografts. Combination of BO-1055 and irinotecan demonstrated synergism in Ewing sarcoma PDX models. Potent activity on sarcoma cells and its relative lack of toxicity presents a strong rationale for further development of BO-1055 as a therapeutic agent. PMID- 27248665 TI - Risk factor compositions of nonalcoholic fatty liver disease change with body mass index in males and females. AB - Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and correlated with obesity. To evaluate the role of body mass index (BMI) and gender difference in NAFLD, 8817 general adult subjects underwent physical examinations and were divided into four groups: underweight, normal, overweight and obese. The risk factor compositions for NAFLD were evaluated in each group by gender. The percentage of subjects with NAFLD increased sharply from 0.4% in the underweight group up to 81.9 % in the obese group. BMI stratification showed distinct risk factor compositions associated with NAFLD in males and females according to BMI and improved the performance of NAFLD prediction models in each group. Triglycerides (TG), alanine transaminase (ALT), aspartate transaminase (AST), and uric acid were steady risk factors for NAFLD in males. Total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), ALT, and uric acid were steady risk factors for NAFLD in females. TG, ALT and uric acid were common risk factors in both genders with high performance for NAFLD discrimination. Our data provide gender- and BMI-specific risk factor compositions that will facilitate individualised treatment and benefit NAFLD control and prevention. PMID- 27248666 TI - Association between the APEX1 Asp148Glu polymorphism and prostate cancer, especially among Asians: a new evidence-based analysis. AB - BACKGROUND: Prostate cancer (Pca) is a serious disease associated with considerable morbidity and mortality. As a causative factor, the Asp148Glu polymorphism has been identified in the apurinic/apyrimidinic endonuclease (APEX1) gene. However, the association among Asians is considered controversial. METHODS: Evidence for this association was obtained from the PubMed, Embase, HuGENet and Chinese National Knowledge Infrastructure (CNKI) databases. In the analysis, four models were applied. Associations between the APEX1 polymorphism and the invasiveness of Pca based on the Gleason score, prostate-specific antigen expression and clinical status were also evaluated. RESULTS: Seven articles were included in the analysis. Positive results were not only discovered in the pooled analysis, but also among patients of mixed descentand Asian descent. However, after considering the Hardy-Weinberg equilibrium (HWE), we observed only a 1.557 fold increase in Pca risk for subjects of Asian descent(GG vs. TT: OR=1.557, 95%CI=1.069-2.268) under the co-dominant model. Additionally, we did not also find any relationship between the APEX1 Asp148Glu polymorphism and invasive Pca risk. CONCLUSION: On the basis of the function of the APEX1 Asp148Glu polymorphism, recent studies, and our results, we suggest that the APEX1 Asp148Glu polymorphism might be important in stimulating the development of Pca rather than its invasiveness in various populations, especially for Asians. PMID- 27248667 TI - Dispositional characteristics, relational well-being and perceived life satisfaction and empowerment of elders. AB - OBJECTIVES: The broad purpose of this research is to identify the key modifiable variables most related to elders' life satisfaction and empowerment in order to improve the efficacy of interventions projects. Our study aims to integrate the theoretical perspectives of personality and community psychology focusing both on dispositional characteristics and relational well-being of elders, investigating triads, composed by an elder, a paid caregiver and the most involved relative. This study explores the impact of (1) some socio-demographic characteristics of elders, (2) some modifiable dispositional variables of elders and (3) elders' relational well-being on elders' empowerment and life satisfaction. METHOD: The study involved 429 people in 143 triads. Semi-structured interviews with elders, paid caregiver and close relatives were used to construct a new pilot measure of elders' relational well-being. Life Satisfaction, Empowerment, Loneliness, Positivity, Humor and Emotions self-efficacy scales were also administered. Hierarchical multiple regressions were performed. RESULTS: Elders' positivity, relational well-being of elders and living alone were significantly related to empowerment. Elders' relational well-being and positivity significantly contributed to life satisfaction. DISCUSSION: Interventions to increase empowerment and life satisfaction should focus primarily on augmenting positivity and relational well-being integrating the theoretical premises of both personality and community psychology. PMID- 27248668 TI - Magnetic Iron Oxide Nanoparticle Seeded Growth of Nucleotide Coordinated Polymers. AB - The introduction of functional molecules to the surface of magnetic iron oxide nanoparticles (NPs) is of critical importance. Most previously reported methods were focused on surface ligand attachment either by physisorption or covalent conjugation, resulting in limited ligand loading capacity. In this work, we report the seeded growth of a nucleotide coordinated polymer shell, which can be considered as a special form of adsorption by forming a complete shell. Among all of the tested metal ions, Fe(3+) is the most efficient for this seeded growth. A diverse range of guest molecules, including small organic dyes, proteins, DNA, and gold NPs, can be encapsulated in the shell. All of these molecules were loaded at a much higher capacity compared to that on the naked iron oxide NP core, confirming the advantage of the coordination polymer (CP) shell. In addition, the CP shell provides better guest protein stability compared to that of simple physisorption while retaining guest activity as confirmed by the entrapped glucose oxidase assay. Use of this system as a peroxidase nanozyme and glucose biosensor was demonstrated, detecting glucose as low as 1.4 MUM with excellent stability. This work describes a new way to functionalize inorganic materials with a biocompatible shell. PMID- 27248669 TI - Analysis of Ligand-Receptor Association and Intermediate Transfer Rates in Multienzyme Nanostructures with All-Atom Brownian Dynamics Simulations. AB - We present the second-generation GeomBD Brownian dynamics software for determining interenzyme intermediate transfer rates and substrate association rates in biomolecular complexes. Substrate and intermediate association rates for a series of enzymes or biomolecules can be compared between the freely diffusing disorganized configuration and various colocalized or complexed arrangements for kinetic investigation of enhanced intermediate transfer. In addition, enzyme engineering techniques, such as synthetic protein conjugation, can be computationally modeled and analyzed to better understand changes in substrate association relative to native enzymes. Tools are provided to determine nonspecific ligand-receptor association residence times, and to visualize common sites of nonspecific association of substrates on receptor surfaces. To demonstrate features of the software, interenzyme intermediate substrate transfer rate constants are calculated and compared for all-atom models of DNA origami scaffold-bound bienzyme systems of glucose oxidase and horseradish peroxidase. Also, a DNA conjugated horseradish peroxidase enzyme was analyzed for its propensity to increase substrate association rates and substrate local residence times relative to the unmodified enzyme. We also demonstrate the rapid determination and visualization of common sites of nonspecific ligand-receptor association by using HIV-1 protease and an inhibitor, XK263. GeomBD2 accelerates simulations by precomputing van der Waals potential energy grids and electrostatic potential grid maps, and has a flexible and extensible support for all-atom and coarse-grained force fields. Simulation software is written in C++ and utilizes modern parallelization techniques for potential grid preparation and Brownian dynamics simulation processes. Analysis scripts, written in the Python scripting language, are provided for quantitative simulation analysis. GeomBD2 is applicable to the fields of biophysics, bioengineering, and enzymology in both predictive and explanatory roles. PMID- 27248670 TI - Sorption/Desorption Behavior and Mechanism of NH4(+) by Biochar as a Nitrogen Fertilizer Sustained-Release Material. AB - Biochar, the pyrolysis product of biomass material with limited oxygen, has the potential to increase crop production and sustained-release fertilizer, but the understanding of the reason for improving soil fertility is insufficient, especially the behavior and mechanism of ammonium sulfate. In this study, the sorption/desorption effect of NH4(+) by biochar deriving from common agricultural wastes under different preparation temperatures from 200 to 500 degrees C was studied and its mechanism was discussed. The results showed that biochar displayed excellent retention ability in holding NH4(+) above 90% after 21 days under 200 degrees C preparation temperature, and it can be deduced that the oxygen functional groups, such as carboxyl and keto group, played the primary role in adsorbing NH4(+) due to hydrogen bonding and electrostatic interaction. The sorption/desorption effect and mechanism were studied for providing an optional way to dispose of agricultural residues into biochar as a nitrogen fertilizer sustained-release material under suitable preparation temperature. PMID- 27248671 TI - Tunnelling in carbonic acid. AB - The cis,trans-conformer of carbonic acid (H2CO3), generated by near-infrared radiation, undergoes an unreported quantum mechanical tunnelling rotamerization with half-lives in cryogenic matrices of 4-20 h, depending on temperature and host material. First-principles quantum chemistry at high levels of theory gives a tunnelling half-life of about 1 h, quite near those measured for the fastest rotamerizations. PMID- 27248673 TI - Combined cell-gene therapy for lung cancer: rationale, challenges and prospects. PMID- 27248683 TI - Expression of MAGE-C1/CT7 provides prognostic information in multiple myeloma. PMID- 27248684 TI - Neuronal autoantibodies in patients with Rasmussen's encephalitis. AB - Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti-neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell-based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures. The mean age at onset of seizures was 8.3+/-3.4 years (range: 4-13.5) and mean follow-up time was 11.2+/-5.4 years (range: 5-19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen-specific anti-neuronal autoimmunity in RE pathophysiology. PMID- 27248685 TI - A Rejoinder. AB - Three commentaries on the Nesselroade and Molenaar target article in this issue are responded to in the interest of elaborating and defending the points of view expressed in our article. The commentaries feature philosophy of science, general structural modeling, and broad behavioral research perspectives. Responding to the commentaries afforded us the opportunity to clarify further matters that we deem critical to the fundamental matter of measurement in behavioral science, especially as it emphasizes (properly, we believe) the individual as the primary unit of analysis. PMID- 27248686 TI - In Vitro Biosynthesis and Substrate Tolerance of the Plantazolicin Family of Natural Products. AB - Plantazolicin (PZN) is a ribosomally synthesized and post-translationally modified peptide (RiPP) natural product that exhibits extraordinarily narrow spectrum antibacterial activity toward the causative agent of anthrax, Bacillus anthracis. During PZN biosynthesis, a cyclodehydratase catalyzes cyclization of cysteine, serine, and threonine residues in the PZN precursor peptide (BamA) to azolines. Subsequently, a dehydrogenase oxidizes most of these azolines to thiazoles and (methyl)oxazoles. The final biosynthetic steps consist of leader peptide removal and dimethylation of the nascent N-terminus. Using a heterologously expressed and purified heterocycle synthetase, the BamA peptide was processed in vitro concordant with the pattern of post-translational modification found in the naturally occurring compound. Using a suite of BamA derived peptides, including amino acid substitutions as well as contracted and expanded substrate variants, the substrate tolerance of the heterocycle synthetase was elucidated in vitro, and the residues crucial for leader peptide binding were identified. Despite increased promiscuity compared to what was previously observed during heterologous production in E. coli, the synthetase retained exquisite selectivity in cyclization of unnatural peptides only at positions which correspond to those cyclized in the natural product. A cleavage site was subsequently introduced to facilitate leader peptide removal, yielding mature PZN variants after enzymatic or chemical dimethylation. In addition, we report the isolation and characterization of two novel PZN-like natural products that were predicted from genome sequences but whose production had not yet been observed. PMID- 27248687 TI - Presence of Extracellular DNA during Biofilm Formation by Xanthomonas citri subsp. citri Strains with Different Host Range. AB - Xanthomonas citri subsp. citri (Xcc) A strain causes citrus bacterial canker, a serious leaf, fruit and stem spotting disease of several Citrus species. X. alfalfae subsp. citrumelonis (Xac) is the cause of citrus bacterial spot, a minor disease of citrus nursery plants and X. campestris pv. campestris (Xc) is a systemic pathogen that causes black rot of cabbage. Xanthomonas spp. form biofilms in planta that facilitate the host infection process. Herein, the role of extracellular DNA (eDNA) was evaluated in the formation and stabilization of the biofilm matrix at different stages of biofilm development. Fluorescence and light microscopy, as well as DNAse treatments, were used to determine the presence of eDNA in biofilms and bacterial cultures. DNAse treatments of Xcc strains and Xac reduced biofilm formation at the initial stage of development, as well as disrupted preformed biofilm. By comparison, no significant effect of the DNAse was detected for biofilm formation by Xc. DNAse effects on biofilm formation or disruption varied among Xcc strains and Xanthomonas species which suggest different roles for eDNA. Variation in the structure of fibers containing eDNA in biofilms, bacterial cultures, and in twitching motility was also visualized by microscopy. The proposed roles for eDNA are as an adhesin in the early stages of biofilm formation, as an structural component of mature bacterial aggregates, and twitching motility structures. PMID- 27248688 TI - Multilocus Phylogeography of the Treefrog Scinax eurydice (Anura, Hylidae) Reveals a Plio-Pleistocene Diversification in the Atlantic Forest. AB - We aim to evaluate the genetic structure of an Atlantic Forest amphibian species, Scinax eurydice, testing the congruence among patterns identified and proposed by the literature for Pleistocene refugia, microrefugia, and geographic barriers to gene flow such as major rivers. Furthermore, we aim to evaluate predictions of such barriers and refugia on the genetic structure of the species, such as presence/absence of dispersal, timing since separation, and population expansions/contractions. We sequenced mitochondrial and nuclear genetic markers on 94 tissue samples from 41 localities. We inferred a gene tree and estimated genetic distances using mtDNA sequences. We then ran population clustering and assignment methods, AMOVA, and estimated migration rates among populations identified through mtDNA and nDNA analyses. We used a dated species tree, skyline plots, and summary statistics to evaluate concordance between population's distributions and geographic barriers and Pleistocene refugia. Scinax eurydice showed high mtDNA divergences and four clearly distinct mtDNA lineages. Species tree and population assignment tests supported the existence of two major clades corresponding to northeastern and southeastern Atlantic Forest in Brazil, each one composed of two other clades. Lineage splitting events occurred from late Pliocene to Pleistocene. We identified demographic expansions in two clades, and inexistent to low levels of migrations among different populations. Genetic patterns and demographic data support the existence of two northern Refuge and corroborate microrefugia south of the Doce/Jequitinhonha Rivers biogeographic divide. The results agree with a scenario of recent demographic expansion of lowland taxa. Scinax eurydice comprises a species complex, harboring undescribed taxa consistent with Pleistocene refugia. Two rivers lie at the boundaries among populations and endorse their role as secondary barriers to gene flow. PMID- 27248689 TI - Non-cereal ingredients for the attenuation of glycaemic response to bread: a review of the clinical evidence. AB - Lowering postprandial blood glucose response remains at the forefront of scientific interest, due to emerging evidence of potential health benefits. Although a large variety of commercial bread products is available, specific postprandial effects of different carbohydrate sources in humans have not been elucidated. The purpose of the present review is to critically record the human studies investigating the efficacy of non-cereal based ingredients on the modulation of glycaemic response to bread. The review of the literature revealed that the substitution of refined flours for legume flours is the main alternative strategy for reducing glycaemic response to bread beyond cereal ingredients. The incorporation of fruit-derived ingredients, specific dietary fibre originating from various sources, and the micronutrient enrichment of bread with trivalent chromium constitute novel and promising strategies for the production of low GI breadstuff. In agreement to the above, bakery industry should focus on technological aspects calculating on the suggested approaches in order to obtain health-promoting bread products based on ingredients originating from non-cereal sources. PMID- 27248690 TI - Refining Pathways: A Model Comparison Approach. AB - Cellular signalling pathways consolidate multiple molecular interactions into working models of signal propagation, amplification, and modulation. They are described and visualized as networks. Adjusting network topologies to experimental data is a key goal of systems biology. While network reconstruction algorithms like nested effects models are well established tools of computational biology, their data requirements can be prohibitive for their practical use. In this paper we suggest focussing on well defined aspects of a pathway and develop the computational tools to do so. We adapt the framework of nested effect models to focus on a specific aspect of activated Wnt signalling in HCT116 colon cancer cells: Does the activation of Wnt target genes depend on the secretion of Wnt ligands or do mutations in the signalling molecule beta-catenin make this activation independent from them? We framed this question into two competing classes of models: Models that depend on Wnt ligands secretion versus those that do not. The model classes translate into restrictions of the pathways in the network topology. Wnt dependent models are more flexible than Wnt independent models. Bayes factors are the standard Bayesian tool to compare different models fairly on the data evidence. In our analysis, the Bayes factors depend on the number of potential Wnt signalling target genes included in the models. Stability analysis with respect to this number showed that the data strongly favours Wnt ligands dependent models for all realistic numbers of target genes. PMID- 27248691 TI - The moral animal: virtue, vice, and human nature. AB - In Leo Tolstoy's famous novella, The Death of Ivan Ilyich, a rich and meaningful inner life is sacrificed in pursuit of material rewards and social status. How can we cultivate something intrinsic that transcends our worldly accomplishments? Assuming that a basic model or map of human nature is needed to navigate the road to the good life, what desires, tendencies, and aversions constitute our core nature? How has our evolutionary history shaped our moral impulses? Are we inherently good or fundamentally flawed? Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion with philosopher Christian Miller, neuroscientist Heather Berlin, and historian of science Michael Shermer to examine our moral ecology and its influence on our underlying assumptions about human nature. PMID- 27248692 TI - Forecasting East Asian Indices Futures via a Novel Hybrid of Wavelet-PCA Denoising and Artificial Neural Network Models. AB - The motivation behind this research is to innovatively combine new methods like wavelet, principal component analysis (PCA), and artificial neural network (ANN) approaches to analyze trade in today's increasingly difficult and volatile financial futures markets. The main focus of this study is to facilitate forecasting by using an enhanced denoising process on market data, taken as a multivariate signal, in order to deduct the same noise from the open-high-low close signal of a market. This research offers evidence on the predictive ability and the profitability of abnormal returns of a new hybrid forecasting model using Wavelet-PCA denoising and ANN (named WPCA-NN) on futures contracts of Hong Kong's Hang Seng futures, Japan's NIKKEI 225 futures, Singapore's MSCI futures, South Korea's KOSPI 200 futures, and Taiwan's TAIEX futures from 2005 to 2014. Using a host of technical analysis indicators consisting of RSI, MACD, MACD Signal, Stochastic Fast %K, Stochastic Slow %K, Stochastic %D, and Ultimate Oscillator, empirical results show that the annual mean returns of WPCA-NN are more than the threshold buy-and-hold for the validation, test, and evaluation periods; this is inconsistent with the traditional random walk hypothesis, which insists that mechanical rules cannot outperform the threshold buy-and-hold. The findings, however, are consistent with literature that advocates technical analysis. PMID- 27248694 TI - Protection of neonates and infants by maternal immunization. PMID- 27248693 TI - Ancient DNA Analysis Suggests Negligible Impact of the Wari Empire Expansion in Peru's Central Coast during the Middle Horizon. AB - The analysis of ancient human DNA from South America allows the exploration of pre-Columbian population history through time and to directly test hypotheses about cultural and demographic evolution. The Middle Horizon (650-1100 AD) represents a major transitional period in the Central Andes, which is associated with the development and expansion of ancient Andean empires such as Wari and Tiwanaku. These empires facilitated a series of interregional interactions and socio-political changes, which likely played an important role in shaping the region's demographic and cultural profiles. We analyzed individuals from three successive pre-Columbian cultures present at the Huaca Pucllana archaeological site in Lima, Peru: Lima (Early Intermediate Period, 500-700 AD), Wari (Middle Horizon, 800-1000 AD) and Ychsma (Late Intermediate Period, 1000-1450 AD). We sequenced 34 complete mitochondrial genomes to investigate the potential genetic impact of the Wari Empire in the Central Coast of Peru. The results indicate that genetic diversity shifted only slightly through time, ruling out a complete population discontinuity or replacement driven by the Wari imperialist hegemony, at least in the region around present-day Lima. However, we caution that the very subtle genetic contribution of Wari imperialism at the particular Huaca Pucllana archaeological site might not be representative for the entire Wari territory in the Peruvian Central Coast. PMID- 27248695 TI - Long Distance Dispersal Potential of Two Seagrasses Thalassia hemprichii and Halophila ovalis. AB - The wide distribution of many seagrasses may be attributable to exploitation of currents. However, many species have seeds heavier than seawater, limiting surface floating, and thus, deep water becomes a potential barrier between suitable habitats. In this investigation, we studied the dispersal potential of various life history stages of two species of seagrasses, Thalassia hemprichii and Halophila ovalis, at Dongsha Atoll and Penghu Islands in Taiwan Strait, west Pacific. The adult plants of both species, often dislodged naturally from substrate by waves, could float, but only that of T. hemprichii could float for months and still remain alive and potentially able to colonize new territories. The seedlings of T. hemprichii could also float for about a month once failing to anchor to substrate of coral sand, but that of H. ovalis could not. The fruits and seeds of T. hemprichii could both float, but for too short a duration to enable long distance travel; those seeds released from long floating fruits had low germination rates in our tests. Obviously, their seeds are not adaptive for long distance dispersal. Fruits and seeds of H. ovalis do not float. The potential of animals as vectors was tested by feeding fruits and seeds of both species to a goose, a duck, and two fish in the laboratory. The fruits and seeds of T. hemprichii were digested and could no longer germinate; those of H. ovalis could pass through the digestive tracts and have a much higher germination rates than uningested controls. Therefore, birds could be important vectors for long distance dispersal of H. ovalis. The two seagrasses adopted very different dispersal mechanisms for long distance travel, and both exploited traits originally adaptive for other purposes. PMID- 27248696 TI - The Dynamics of Disease Progression in Cystic Fibrosis. AB - In cystic fibrosis, statistical models have been more successful in predicting mortality than the time course of clinical status. We develop a system of partial differential equations that simultaneously track mortality and patient status, with all model parameters estimated from the extensive and carefully maintained database from the Cystic Fibrosis Foundation. Cystic fibrosis is an autosomal recessive disease that leads to loss of lung function, most commonly assessed using the Forced Expiratory Volume in 1 second (FEV1%). This loss results from inflammation secondary to chronic bacterial infections, particularly Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus (MSSA) and members of the virulent Burkholderia complex. The model tracks FEV1% and carriage of these three bacteria over the course of a patient's life. Analysis of patient state changes from year to year reveals four feedback loops: a damaging positive feedback loop between P. aeruginosa carriage and lower FEV1%, negative feedback loops between P. aeruginosa and MSSA and between P. aeruginosa and Burkholderia, and a protective positive feedback loop between MSSA carriage and higher FEV1%. The partial differential equations built from this data analysis accurately capture the life-long progression of the disease, quantify the key role of high annual FEV1% variability in reducing survivorship, the relative unimportance of short term bacterial interactions for long-term survival, and the potential benefits of eradicating the most harmful bacteria. PMID- 27248697 TI - Correction: Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney. AB - [This corrects the article DOI: 10.1371/journal.pone.0153422.]. PMID- 27248698 TI - Quantitative IR microscopy and spectromics open the way to 3D digital pathology. AB - Currently, only mass-spectrometry (MS) microscopy brings a quantitative analysis of chemical contents of tissue samples in 3D. Here, the reconstruction of a 3D quantitative chemical images of a biological tissue by FTIR spectro-microscopy is reported. An automated curve-fitting method is developed to extract all intense absorption bands constituting IR spectra. This innovation benefits from three critical features: (1) the correction of raw IR spectra to make them quantitatively comparable; (2) the automated and iterative data treatment allowing to transfer the IR-absorption spectrum into a IR-band spectrum; (3) the reconstruction of an 3D IR-band matrix (x, y, z for voxel position and a 4th dimension with all IR-band parameters). Spectromics, which is a new method for exploiting spectral data for tissue metadata reconstruction, is proposed to further translate the related chemical information in 3D, as biochemical and anatomical tissue parameters. An example is given with oxidative stress distribution and the reconstruction of blood vessels in tissues. The requirements of IR microscopy instrumentation to propose 3D digital histology as a clinical routine technology is briefly discussed. PMID- 27248699 TI - Frontal fibrosing alopecia: a disease fascinating for the researcher, disappointing for the clinician and distressing for the patient. PMID- 27248700 TI - Symptom load and individual symptoms before and after repair of parastomal hernia: a prospective single centre study. AB - AIM: The symptom load and individual symptoms before and after repair of parastomal hernia were investigated. METHOD: Stoma-related symptoms were prospectively recorded before repair of a parastomal hernia and at 10 days and 6 months postoperatively: leakage, skin problems, difficulty with the appliance, limitation of activity, difficulty with clothing, cosmetic complaints, social restriction, erratic action of the stoma, a bearing-down sensation at the site of the stoma and pain. Episodes of intermittent bowel obstruction and difficulty with irrigation were also recorded. Patients were seen at 1, 2 and 3 years and were examined for recurrent parastomal herniation. RESULTS: Of 131 consecutive patients referred to a specialized centre for treatment of parastomal bulging, 61 underwent parastomal hernia repair. Forty-eight patients were treated with the Sugarbaker technique. Six different symptoms were present in more than half the patients before surgery. The overall symptom load decreased significantly from a median of 4 [interquartile range (IQR) 2.5-6] preoperatively to 2 (IQR 1-3) on postoperative day 10 and 1 (IQR 0-2) at 6 months, P < 0.001. The number of symptoms decreased in 93% of patients; in 5% there was no change and in 2% symptoms increased. Skin problems and leakage were the only symptoms that were not significantly reduced. The overall recurrence rate of herniation was 5/48 (10%) at a median of 12 (IQR 6-24) months. CONCLUSION: The preoperative symptom load was high and this fell after repair in over 90% of patients. Recurrence occurred in 10% of patients within 2 years of repair. The study emphasizes the importance of detailed knowledge of the symptoms of parastomal hernia when addressing and managing patients' problems and complaints. PMID- 27248701 TI - Adverse effect of smoking on prognosis in human papillomavirus-associated oropharyngeal carcinoma. AB - BACKGROUND: The purpose of this retrospective study was to identify prognostic factors in a cohort of patients with oropharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT). METHODS: Medical records of 142 patients treated with (chemo)radiotherapy between September 2005 and September 2011 were reviewed and the human papillomavirus (HPV) status was determined by polymerase chain reaction (PCR) analysis. Potential prognostic factors for 3-year locoregional control and overall survival (OS) were evaluated. RESULTS: HPV positive patients (n = 82) had locoregional control and OS of 78% and 79%, respectively. Significant prognostic factors on multivariate analysis were smoking (p = .03) for locoregional control and OS, and comorbidity (p = .04) for OS. Further stratification was done according to smoking behavior in HPV-positive patients. Locoregional control in current smokers was 67% compared to 86% in never smokers and former smokers, respectively (p = .02). CONCLUSION: Smoking was the only modifiable prognostic factor in HPV-positive patients. Therefore, active stop-smoking programs must be integrated in the routine management of patients to maximize treatment results. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1780 1787, 2016. PMID- 27248702 TI - Impact of end-stage renal disease on hospital outcomes among patients admitted to intensive care units: A retrospective matched-pair cohort study. AB - AIM: We aimed to estimate the burden of end-stage renal disease (ESRD) among patients admitted to intensive care units (ICUs), by comparing hospital outcomes between patients with and without ESRD. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients aged 20 years or older who were admitted to ICUs for >=3 days (2 nights) in 2011. We created a matched cohort of patients with and without ESRD for hospital, age, sex, main diagnosis category, and ICU admission type (medical or surgical) at a maximum ratio of 1:3. For these matched patients, we compared patient characteristics, treatment regimens at ICU admission, and hospital outcomes. We also performed a multivariable logistic regression analysis for the associations between ESRD and 28-day (counting from ICU admission) and in-hospital mortality. RESULTS: Among the 164 423 eligible patients, 7998 (4.9%) had ESRD, from which 5228 ESRD and 12 274 non-ESRD patients were matched for the aforementioned factors. Compared to non-ESRD patients, ESRD patients were on more intensive treatment regimens, including mechanical ventilation, vasoactive drugs, and blood transfusion. Patients with ESRD showed significantly higher ICU, 28-day, and in-hospital mortality and longer lengths of stay in the ICU and hospital (28-day mortality: 11.7% vs. 8.3%; P < 0.001, in-hospital mortality: 21.1% vs. 12.0%; P < 0.001). After adjusting for confounding factors, ESRD was independently associated with 28-day mortality (adjusted odds ratio: 1.36, 95% confidence interval [CI]: 1.22 1.52) and in-hospital mortality (adjusted odds ratio: 1.85, 95% CI: 1.69-2.02). CONCLUSION: This study involving the Japanese national inpatient database, with a matched-pair cohort design, suggested that ESRD is an important burden in the critical care setting. PMID- 27248703 TI - "We are what our bacteria eat": The role of bacteria in personalizing nutrition therapy in gastrointestinal conditions. AB - The theme for the 2016 World Digestive Health Day is "Your Diet and Gut Health". The World Gastroenterology Organization thereby wishes to raise awareness of the relationship between what we eat and gastrointestinal symptoms. World Digestive Health Day (WDHD) is celebrated each year on May 29. This brief review article on behalf of the New Zealand Society of Gastroenterology will highlight recent developments in this highly active area of research with a special emphasis on gastrointestinal disorders. PMID- 27248704 TI - Training-Load-Guided vs Standardized Endurance Training in Recreational Runners. AB - PURPOSE: To compare the effects of a standardized endurance-training program with individualized endurance training modified based on the cumulative training load provided by the Polar training-load feature. METHODS: After 12 wk of similar training, 24 recreationally endurance-trained men were matched to a training-load guided (TL, n = 10) or standardized (ST, n = 14) group and continued training for 12 wk. In TL, training sessions were individually chosen daily based on an estimated cumulative training load, whereas in ST the training was standardized with 4-6 sessions/wk. Endurance performance (shortest 1000-m running time during an incremental field test of 6 * 1000 m) and heart-rate variability (HRV) were measured every 4 wk, and maximal oxygen consumption (VO2max) was measured during an incremental treadmill test every 12 wk. RESULTS: During weeks 1-12, similar changes in VO2max and 1000-m time were observed in TL (+7% +/- 4%, P = .004 and 6% +/- 4%, P = .069) and ST (+5% +/- 7%, P = .019 and -8% +/- 5%, P < .001). During wk 13-24, VO2max statistically increased in ST only (3% +/- 4%, P = .034). The 1000-m time decreased in TL during wk 13-24 (-9% +/- 5%, P = .011), but in ST only during wk 13-20 (-3% +/- 2%, P = .003). The overall changes in VO2max and 1000-m time during wk 0-24 were similar in TL (+7% +/- 4%, P = .001 and -9% +/- 5%, P = .011) and ST (+10% +/- 7%, P < .001 and -13% +/- 5%, P < .001). No between-groups differences in total training volume and frequency were observed. HRV remained statistically unaltered in both groups. CONCLUSIONS: The main finding was that training performed according to the cumulative training load led to improvements in endurance performance similar to those with standardized endurance training in recreational endurance runners. PMID- 27248705 TI - A GROMOS-Compatible Force Field for Small Organic Molecules in the Condensed Phase: The 2016H66 Parameter Set. AB - This article reports on the calibration and validation of a new GROMOS-compatible parameter set 2016H66 for small organic molecules in the condensed phase. The calibration is based on 62 organic molecules spanning the chemical functions alcohol, ether, aldehyde, ketone, carboxylic acid, ester, amine, amide, thiol, sulfide, and disulfide, as well as aromatic compounds and nucleic-acid bases. For 57 organic compounds, the calibration targets are the experimental pure-liquid density rholiq and the vaporization enthalpy DeltaHvap, as well as the hydration free energy DeltaGwat and the solvation free energy DeltaGche in cyclohexane, at atmospheric pressure and at (or close to) room temperature. The final root-mean square deviations (RMSD) for these four quantities over the set of compounds are 32.4 kg m(-3), 3.5 kJ mol(-1), 4.1 kJ mol(-1), and 2.1 kJ mol(-1), respectively, and the corresponding average deviations (AVED) are 1.0 kg m(-3), 0.2 kJ mol(-1), 2.6 kJ mol(-1), and 1.0 kJ mol(-1), respectively. For the five nucleic-acid bases, the parametrization is performed by transferring the final 2016H66 parameters from analogous organic compounds followed by a slight readjustment of the charges to reproduce the experimental water-to-chloroform transfer free energies DeltaGtrn. The final RMSD for this quantity over the five bases is 1.7 kJ mol(-1), and the corresponding AVED is 0.8 kJ mol(-1). As an initial validation of the 2016H66 set, seven additional thermodynamic, transport, and dielectric properties are calculated for the 57 organic compounds in the liquid phase. The agreement with experiment in terms of these additional properties is found to be reasonable, with significant deviations typically affecting either a specific chemical function or a specific molecule. This suggests that in most cases, a classical force-field description along with a careful parametrization against rholiq, DeltaHvap, DeltaGwat, and DeltaGche results in a model that appropriately describes the liquid in terms of a wide spectrum of its physical properties. PMID- 27248706 TI - Alteration of the Intra- and Cross- Hemisphere Posterior Default Mode Network in Frontal Lobe Glioma Patients. AB - Patients with frontal lobe gliomas often experience neurocognitive dysfunctions before surgery, which affects the default mode network (DMN) to different degrees. This study quantitatively analyzed this effect from the perspective of cerebral hemispheric functional connectivity (FC). We collected resting-state fMRI data from 20 frontal lobe glioma patients before treatment and 20 healthy controls. All of the patients and controls were right-handed. After pre processing the images, FC maps were built from the seed defined in the left or right posterior cingulate cortex (PCC) to the target regions determined in the left or right temporal-parietal junction (TPJ), respectively. The intra- and cross-group statistical calculations of FC strength were compared. The conclusions were as follows: (1) the intra-hemisphere FC strength values between the PCC and TPJ on the left and right were decreased in patients compared with controls; and (2) the correlation coefficients between the FC pairs in the patients were increased compared with the corresponding controls. When all of the patients were grouped by their tumor's hemispheric location, (3) the FC of the subgroups showed that the dominant hemisphere was vulnerable to glioma, and (4) the FC in the dominant hemisphere showed a significant correlation with WHO grade. PMID- 27248707 TI - Fast escape of a quantum walker from an integrated photonic maze. AB - Escaping from a complex maze, by exploring different paths with several decision making branches in order to reach the exit, has always been a very challenging and fascinating task. Wave field and quantum objects may explore a complex structure in parallel by interference effects, but without necessarily leading to more efficient transport. Here, inspired by recent observations in biological energy transport phenomena, we demonstrate how a quantum walker can efficiently reach the output of a maze by partially suppressing the presence of interference. In particular, we show theoretically an unprecedented improvement in transport efficiency for increasing maze size with respect to purely quantum and classical approaches. In addition, we investigate experimentally these hybrid transport phenomena, by mapping the maze problem in an integrated waveguide array, probed by coherent light, hence successfully testing our theoretical results. These achievements may lead towards future bio-inspired photonics technologies for more efficient transport and computation. PMID- 27248709 TI - Joint Decision Making and Reduced Need for Compulsory Psychiatric Admission. PMID- 27248710 TI - Requirements for comprehensive pharmacogenetic genotyping platforms. AB - Recent research highlighted the large extent of rare variants in pharmacogenes and, on this basis, it was estimated that rare variants account for 30-40% of the functional variability in pharmacogenes. It has been proposed that comprehensive next-generation sequencing (NGS)-based sequencing of pharmacogenes could soon be a cost-effective methodology for clinical routine genotyping. Yet, multiple challenges on technical, interpretative and ethical levels need to be overcome to enable the reasonable dissemination of comprehensive pharmacogenetic genotyping, that includes rare genetic variation, into clinical practice. We argue that current pre-emptive pharmacogenetic testing cannot be based on comprehensive approaches but needs to be restricted to validated variants. Rather, comprehensive strategies should only be used for retrospective analyses of patients exhibiting unanticipated drug responses. Thereby, subsequent to computational analyses and functional validations, emerging variants with confirmed functional relevance can be incorporated into candidate genotyping strategies, thus refining and enhancing future pre-emptive genetic testing. PMID- 27248712 TI - Next stop for the CRISPR revolution: RNA-guided epigenetic regulators. AB - Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR associated (Cas) proteins offer a breakthrough platform for cheap, programmable, and effective sequence-specific DNA targeting. The CRISPR-Cas system is naturally equipped for targeted DNA cutting through its native nuclease activity. As such, groups researching a broad spectrum of biological organisms have quickly adopted the technology with groundbreaking applications to genomic sequence editing in over 20 different species. However, the biological code of life is not only encoded in genetics but also in epigenetics as well. While genetic sequence editing is a powerful ability, we must also be able to edit and regulate transcriptional and epigenetic code. Taking inspiration from work on earlier sequence-specific targeting technologies such as zinc fingers (ZFs) and transcription activator-like effectors (TALEs), researchers quickly expanded the CRISPR-Cas toolbox to include transcriptional activation, repression, and epigenetic modification. In this review, we highlight advances that extend the CRISPR-Cas toolkit for transcriptional and epigenetic regulation, as well as best practice guidelines for these tools, and a perspective on future applications. PMID- 27248711 TI - Antigenic Relationships among Human Pathogenic Orientia tsutsugamushi Isolates from Thailand. AB - BACKGROUND: Scrub typhus is a common cause of undiagnosed febrile illness in certain tropical regions, but can be easily treated with antibiotics. The causative agent, Orientia tsutsugamushi, is antigenically variable which complicates diagnosis and efforts towards vaccine development. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to dissect the antigenic and genetic relatedness of O. tsutsugamushi strains and investigate sero-diagnostic reactivities by titrating individual patient sera against their O. tsutsugamushi isolates (whole-cell antigen preparation), in homologous and heterologous serum isolate pairs from the same endemic region in NE Thailand. The indirect immunofluorescence assay was used to titrate Orientia tsutsugamushi isolates and human sera, and a mathematical technique, antigenic cartography, was applied to these data to visualise the antigenic differences and cross-reactivity between strains and sera. No functional or antigen-specific analyses were performed. The antigenic variation found in clinical isolates was much less pronounced than the genetic differences found in the 56kDa type-specific antigen genes. The Karp-like sera were more broadly reactive than the Gilliam-like sera. CONCLUSIONS/SIGNIFICANCE: Antigenic cartography worked well with scrub typhus indirect immunofluorescence titres. The data from humoral responses suggest that a Karp-like strain would provide broader antibody cross-reactivity than a Gilliam like strain. Although previous exposure to O. tsutsugamushi could not be ruled out, scrub typhus patient serum antibody responses were characterised by strong homologous, but weak heterologous antibody titres, with little evidence for cross reactivity by Gilliam-like sera, but a broader response from some Karp-like sera. This work highlights the importance of antigenic variation in O. tsutsugamushi diagnosis and determination of new serotypes. PMID- 27248713 TI - Reducing the use of out-of-hours primary care services: A survey among Dutch general practitioners. AB - BACKGROUND: Out-of-hours primary care services have a high general practitioner (GP) workload with increasing costs, while half of all contacts are non-urgent. OBJECTIVES: To identify views of GPs to influence the use of the out-of-hours GP cooperatives. METHODS: Cross-sectional survey study among a random sample of 800 GPs in the Netherlands. RESULTS: Of the 428 respondents (53.5% response rate), 86.5% confirmed an increase in their workload and 91.8% felt that the number of patient contacts could be reduced. A total of 75.4% GP respondents reported that the 24-h service society was a 'very important' reason why patients with non urgent problems attended the GP cooperative; the equivalent for worry or anxiety was 65.8%, and for easy accessibility, 60.1%. Many GPs (83.9%) believed that the way telephone triage is currently performed contributes to the high use of GP cooperatives. Measures that GPs believed were both desirable and effective in reducing the use of GP cooperatives included co-payment for patients, stricter triage, and a larger role for the telephone consultation doctor. GPs considered patient education, improved telephone accessibility of daytime general practices, more possibilities for same-day appointments, as well as feedback concerning the use of GP cooperatives to practices and triage nurses also desirable, but less effective. CONCLUSION: This study provides several clues for influencing the use of GP cooperatives. Further research is needed to examine the impact and safety of these strategies. [Box: see text]. PMID- 27248714 TI - Mixed-Metal Zeolitic Imidazolate Frameworks and their Selective Capture of Wet Carbon Dioxide over Methane. AB - A presynthesized, square planar copper imidazole complex, [Cu(imidazole)4](NO3)2, was utilized as a precursor in the synthesis of a new series of zeolitic imidazolate frameworks, termed ZIF-202, -203, and -204. The structures of all three members were solved by single-crystal X-ray diffraction analysis, which revealed ZIF-203 and -204 having successfully integrated square planar units within the backbones of their respective frameworks. As a result of this unit, the structures of both ZIF-203 and -204 were found to adopt unprecedented three dimensional nets, namely, ntn and thl, respectively. One member of this series, ZIF-204, was demonstrated to be highly porous, exhibit exceptional stability in water, and selectively capture CO2 over CH4 under both dry and wet conditions without any loss in performance over three cycles. Remarkably, the regeneration of ZIF-204 was performed under the mild conditions of flowing a pure N2 gas through the material at ambient temperature. PMID- 27248715 TI - Supramolecular Self-Assembly into Biofunctional Soft Nanotubes: From Bilayers to Monolayers. AB - The inner and outer surfaces of bilayer-based lipid nanotubes can be hardly modified selectively by a favorite functional group. Monolayer-based nanotubes display a definitive difference in their inner and outer functionalities if bipolar wedge-shaped amphiphiles, so-called bolaamphiphiles, as a constituent of the monolayer membrane pack in a parallel fashion with a head-to-tail interface. To exclusively form unsymmetrical monolayer lipid membranes, we focus herein on the rational molecular design of bolaamphiphiles and a variety of self-assembly processes into tubular architectures. We first describe the importance of polymorph and polytype control and then discuss diverse methodologies utilizing a polymer template, multiple hydrogen bonds, binary and ternary coassembly, and two step self-assembly. Novel biologically important functions of the obtained soft nanotubes, brought about only by completely unsymmetrical inner and outer surfaces, are discussed in terms of protein refolding, drug nanocarriers, lectin detection, a chiral inducer for achiral polymers, the tailored fabrication of polydopamine, and spontaneous nematic alignment. PMID- 27248716 TI - Effects of wheelchair Tai Chi on physical and mental health among elderly with disability. AB - A 12-week Wheelchair Tai Chi 10 Form (WTC10) intervention was conducted among elderly with disability to examine the effect of this WTC10 intervention on selected physical and mental health variables. Thirteen (age 87.23 +/- 6.71) in the WTC10 intervention group and 15 (age 89.73 +/- 6.31) in the control group completed the study. Independent t-tests and paired t-tests were employed to examine the differences between groups and within groups, respectively, at pretest and post-test. The WTC10 intervention group showed significant improvements in systolic and diastolic blood pressure, shoulder external rotation, left trunk rotation and total trunk rotation after the intervention. A 12-week WTC10 intervention had positive effects on blood pressure, range of motion at the shoulder and trunk, physical activity, and mental health among the elderly with disability. WTC10 is a feasible and safe exercise for the elderly with disability. PMID- 27248764 TI - Incorrect Table Entries and Word. PMID- 27248765 TI - Impact of Obesity on Robot-Assisted Distal Pancreatectomy. AB - BACKGROUND: Obesity has been steadily increasing in the United States. The effect of body mass index (BMI) on surgical outcomes in pancreatic surgery is still controversial. Currently, there is no report related to obesity and robotic pancreatic surgery. The purpose of this study was to evaluate the impact of BMI on the surgical outcomes of both nonobese and obese patients undergoing robot assisted distal pancreatectomy (RADP). METHODS: A prospectively collected database for RADP was retrieved for analysis. Patients were categorized as obese (BMI >=30 kg/m(2)) and nonobese (BMI <30 kg/m(2)). Demographics, perioperative data, American Society of Anesthesiologists score, diagnosis, conversion rate, morbidity, surgical mortality, pancreatic fistula rate, and length of stay were compared. RESULTS: A total for 85 RADP were included, with 57 (67%) in the nonobese group and 28 (33%) in the obese group. No differences were found between nonobese and obese patients regarding demographic, preoperative risk, and perioperative parameters and mortality. There was a trend in the obese group associated with a higher rate of postoperative complications, but it was statistically insignificant. Clinically significant pancreatic fistula (grade B) occurred in 28.5% of obese patients and in 7% of nonobese patients, but without statistical significance (P = .064). CONCLUSIONS: Obesity does not have a significant impact on the perioperative outcomes and surgical risks for patients undergoing RADP, but high BMI may be a predictor for pancreatic fistula after RADP. PMID- 27248766 TI - Policy Section. PMID- 27248767 TI - Medicolegal-Malpractice and Ethical Issues in Radiology. PMID- 27248768 TI - Effect of 3-Dimensional Vision on Surgeons Using the da Vinci Robot for Laparoscopy: More Than Meets the Eye. PMID- 27248769 TI - Random start or emergency IVF/in vitro maturation: a new rapid approach to fertility preservation. AB - There is a need to develop rapid protocols for ovarian stimulation for women who wish to preserve their fertility following diagnosis of cancer. Conventional gonadotropin stimulation protocols are lengthy and are delayed until the start of the next menstrual period, potentially compromising cancer treatments. The development of random start IVF/in vitro maturation has made significant strides for enabling couples undergoing cancer therapy to achieve a family. However, several unanswered questions still remain. What do we know about the endocrinology of stimulating ovarian follicular activity outside the established protocols of stimulation during the follicular phase? This article explores what is known about antral follicle development during the menstrual cycle, novel ovarian stimulation proposals for optimizing assisted reproductive therapies in women, and direction. PMID- 27248770 TI - Making Sense of Carcinogens: A New Method for Navigating Mechanistic Data. PMID- 27248772 TI - Use of auto-segmentation in the delineation of target volumes and organs at risk in head and neck. AB - BACKGROUND: Manual delineation of structures in head and neck cancers is an extremely time-consuming and labor-intensive procedure. With centers worldwide moving towards the use of intensity-modulated radiotherapy and adaptive radiotherapy, there is a need to explore and analyze auto-segmentation (AS) software, in the search for a faster yet accurate method of structure delineation. MATERIAL AND METHODS: A search for studies published after 2005 comparing AS and manual delineation in contouring organ at risks (OARs) and target volume for head and neck patients was conducted. The reviewed results were then categorized into arguments proposing and opposing the review title. RESULTS: Ten studies were reviewed and derived results were assessed in terms of delineation time-saving ability and extent of delineation accuracy. The influence of other external factors (observer variability, AS strategies adopted and stage of disease) were also considered. Results were conflicting with some studies demonstrating great potential in replacing manual delineation whereas other studies illustrated otherwise. Six of 10 studies investigated time saving; the largest time saving reported being 59%. However, one study found that additional time of 15.7% was required for AS. Four studies reported AS contours to be between 'reasonably good' and 'better quality' than the clinically used contours. Remaining studies cited lack of contrast, AS strategy used and the need for physician intervention as limitations in the standardized use of AS. DISCUSSION: The studies demonstrated significant potential of AS as a useful delineation tool in contouring target volumes and OARs in head and neck cancers. However, it is evident that AS cannot totally replace manual delineation in contouring some structures in the head and neck and cannot be used independently without human intervention. It is also emphasized that delineation studies should be conducted locally so as to evaluate the true value of AS in head and neck cancers in a specific center. PMID- 27248771 TI - Alternative Macrophage Activation Is Increased in Asthma. AB - The immune responses of type 2 T helper cells (Th2) play an important role in asthma and promote the differentiation of alternatively activated (M2) macrophages. M2 macrophages have been increasingly understood to contribute to Th2 immunity. We hypothesized that M2 macrophages are altered in asthma and modulate Th2 responses. The aim of this study was to characterize the phenotype and function of human monocyte-derived M2 and bronchoalveolar lavage fluid (BALF) macrophages from healthy control subjects and subjects with asthma. Phenotypic characteristics and effector function of M2 macrophages were examined using monocyte-derived and BALF macrophages obtained from subjects with asthma (n = 28) and healthy volunteers (n = 9) by flow cytometry and quantitative PCR. Resting monocyte-derived (M0) and M2 macrophages were generated by the addition of macrophage colony-stimulating factor or macrophage colony-stimulating factor plus IL-4, respectively. M2 macrophage cytokine expression and their impact on dendritic and CD4+ T cell activation were examined in vitro. High levels of CD206 and major histocompatibility complex class II expression identify macrophages with an M2 phenotype that are increased 2.9-fold in the BALF of subjects with asthma compared with control subjects. M2 macrophages have elevated IL-6, IL-10, and IL-12p40 production compared with conventional macrophages and modulate dendritic and CD4+ T cell interactions. Histamine receptor 1 and E-cadherin expression identify M2 macrophage subsets associated with increased airflow obstruction. M2 macrophages have a distinct cell surface and effector phenotype and are found in increased numbers in subjects with asthma. These findings suggest that M2 macrophages may play an important role in allergic asthma through their bidirectional interactions with immune and structural cells, and inflammatory mediators. PMID- 27248773 TI - The Worst Thrush I Have Ever Seen. AB - A neonate developed oral lesions during treatment of thrush with gentian violet. The medication was applied by his mother according to the instructions on the bottle she bought over the counter. The literature is briefly reviewed and it is suggested that the availability of this solution without medical supervision should be reconsidered. PMID- 27248774 TI - The Great Pretender: Pediatric Wandering Spleen: Two Case Reports and Review of the Literature. AB - Wandering spleen is a rare condition, typically not only due to embryological defects of the splenic ligaments, but also secondary to trauma and splenomegaly. The most common presentation is acute abdomen with a mobile abdominal mass or recurrent abdominal pain. However, the spleen may be temporary in its normal position, and patients could be asymptomatic. A familiarity, if present, strengthens the diagnostic suspect.Abdominal ultrasonography and computed tomography are the examination of choice, and the management is surgical. PMID- 27248775 TI - Torticollis as the Presenting Sign of Cervical Spondylodiscitis. AB - Acquired torticollis is a common clinical finding in children evaluated in the pediatric emergency department. It may be the presentation symptom of different illnesses, such as trauma, muscle contraction, infections, or malignancies, and an accurate differential diagnosis is required to correctly identify the cause and choose the right treatment. Spondylodiscitis is a low-grade bacterial infection that involves intervertebral disks and the adjacent vertebral bodies. Spondylodiscitis of the cervical spine is unusual and may be a rare cause of torticollis. We report the case of a 4-year-old male patient admitted to the emergency department for a 5-day history of painful torticollis. Blood tests showed an elevated erythrocyte sedimentation rate. The radiograph of the cervical spine showed a thin fifth cervical soma. The magnetic resonance imaging of cervical spine showed the alteration of cervical vertebral bodies and intervertebral disks, suggesting the diagnosis of cervical spondylodiscitis. The patient recovered after endovenous antibiotic treatment. We suggest that cervical spondylodiscitis should be suspected and investigated by means of an magnetic resonance imaging in every case of unexplained torticollis with persisting symptoms. PMID- 27248776 TI - Reasons for Energy Drink Use and Reported Adverse Effects Among Adolescent Emergency Department Patients. AB - OBJECTIVES: There is concern of energy drink use by adolescents. The objective of this study was to evaluate the energy drink consumption use, frequency, age of first use, reasons for use, influences of choice of brand, and adverse events recorded in a predominant Latino adolescent population. METHODS: Subjects between the ages of 13 and 19 years utilizing emergency department services for any reason at a large county hospital answered a questionnaire about energy drink usage. RESULTS: There were 192 subjects, of which 49% were male and 51% were female. Latino adolescents were 85% of the participants, although other ethnic groups participated including African American, white, and Asian. Reasons for use include 61% to increase energy, 32% as study aide, 29% to improve sports performance, and 9% to lose weight. Twenty-four percent reported using energy drinks with ethanol or illicit drugs including marijuana, cocaine, and methamphetamine. Adverse reactions were reported in 40% of the subjects including insomnia (19%), feeling "jittery" (19%), palpitations (16%), gastrointestinal upset (11%), headache (8%), chest pain (5%), shortness of breath (4%), and seizures (1%). CONCLUSIONS: Both brand name and packaging influenced the choice of energy drink in most subjects. Forty percent reported at least 1 adverse effect. While most adverse effects were not severe, a small number are serious. In addition, we showed intentional ingestion with ethanol and illicit drugs. Of additional concern is that both brand and packaging seem to directly affect choice of energy drink consumed. PMID- 27248777 TI - Acute Exertional Compartment Syndrome in Young Athletes: A Descriptive Case Series and Review of the Literature. AB - OBJECTIVES: Acute exertional compartment syndrome (AECS) is a rare presentation of acute compartment syndrome (ACS) after exertion without injury. Unfamiliarity with this entity can lead to delay in diagnosis. The purpose of this study was to increase awareness of AECS and illustrate the morbidities associated with delayed diagnosis. METHODS: With institutional review board approval, we conducted a retrospective chart review of all patients who underwent emergent fasciotomies for AECS from 1997-2013 at our institution. Male patients with sports-related closed fractures of the tibia leading to ACS were identified for comparison. Demographic variables, patient-specific factors, treatment, and outcome characteristics were analyzed. RESULTS: Seven male patients (mean age, 17 years) presented to our institution with AECS from 1997-2013, and 9 patients with fracture-related ACS were selected for comparison. All cases of AECS occurred in the leg. In the AECS group, the mean time from symptom onset to diagnosis was 97 hours. Four patients initially had a missed diagnosis. On presentation, 6 of 7 patients experienced neurologic symptoms (motor or sensory deficit), although none had perfusion deficits. The mean compartment pressure was 91 mm Hg. They all underwent isolated anterior and lateral compartment releases (except for 1 patient who required a 4-compartment release) and required a mean of 4 surgeries. The mean follow-up was 270 days. Of the 4 patients with missed diagnoses, 2 had significant neurologic and functional deficits at final follow-up. The other 5 patients had a full recovery. Fracture-related ACS patients were younger, with quicker time from symptom onset to surgery, and required more compartments to be decompressed at surgery. CONCLUSIONS: Despite the rarity of AECS, orthopedists as well as primary care, emergency medicine, and sports medicine physicians should maintain a high index of suspicion when examining a patient with leg pain out of proportion to examination after exertion. Delay in diagnosis of AECS is associated with substantial muscle necrosis and morbidity. PMID- 27248778 TI - Barriers and Facilitators to Implementing the HEADS-ED: A Rapid Screening Tool for Pediatric Patients in Emergency Departments. AB - OBJECTIVES: This study sought to identify barriers and facilitators to the implementation of the HEADS-ED, a screening tool appropriate for use in the emergency department (ED) that facilitates standardized assessments, discharge planning, charting, and linking pediatric mental health patients to appropriate community resources. METHODS: A qualitative theory-based design was used to identify barriers and facilitators to implementing the HEADS-ED tool. Focus groups were conducted with participants recruited from 6 different ED settings across 2 provinces (Ontario and Nova Scotia). The Theoretical Domains Framework was used as a conceptual framework to guide data collection and to identify themes from focus group discussions. RESULTS: The following themes spanning 12 domains were identified as reflective of participants' beliefs about the barriers and facilitators to implementing the HEADS-ED tool: knowledge, skills, beliefs about capabilities, social professional role and identity, optimism, beliefs about consequences, reinforcement, environmental context and resources, social influences, emotion, behavioral regulation and memory, and attention and decision process. CONCLUSIONS: The HEADS-ED has the potential to address the need for better discharge planning, complete charting, and standardized assessments for the increasing population of pediatric mental health patients who present to EDs. This study has identified potential barriers and facilitators, which should be considered when developing an implementation plan for adopting the HEADS-ED tool into practice within EDs. PMID- 27248779 TI - Time to Bone Healing After Intraosseous Placement in Children is Ill Defined. AB - Time to bone healing after intraosseous (IO) insertion in children has not been clearly established. This report documents the case of a 23-month-old male infant with previous IO placement of the tibia, presenting 3 weeks later to our emergency department with radiographic evidence of previous IO insertion. This report reviews relevant literature on complications of IO insertion, contraindications to IO insertion, and evidentiary support for such recommendations. Time to bone healing after IO insertion and recommendations regarding time to safe cannulation of previously cannulated areas are based on animal models. This case demonstrates 1 instance in which radiographic evidence of bone healing at 3 weeks after IO insertion is not complete, in contradiction to previously reported data. Although the clinical significance of this finding is unknown, further work is needed to define safe timing for IO reinsertion in children. PMID- 27248780 TI - A de-novo large deletion of 2.8 kb produced in the ABCD1 gene causing adrenoleukodystrophy disease. AB - X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene, which encodes an ATP-binding cassette transporter protein, ALDP. The disease is characterized by increased concentrations of very long chain fatty acids (VLCFAs) in plasma, adrenal, testicular, and nerve tissues. For this study, our objective was to conduct clinical, molecular, and genetic studies of a Tunisian patient with X-ALD. The diagnosis was based on clinical indications, biochemical analyses, typical brain-scan patterns, and molecular biology; the molecular analyses were based on PCR, long-range PCR, and sequencing. The molecular analysis by long-range PCR and direct sequencing of the ABCD1 gene showed the presence of a de-novo 2794 bp deletion covering the whole of exon 2. Using bioinformatics tools, we demonstrate that the large deletion is located in a region rich with Alu sequences. Furthermore, we suggest that the AluJb sequence could be the cause of the large deletion of intron 1, exon 2, and intron 2, and the creation of a premature stop codon within exon 3. This report is the first report in which we demonstrate the breakpoints and the size of a large deletion in a Tunisian with X-ALD. PMID- 27248781 TI - Design of a Small-Molecule Drug Conjugate for Prostate Cancer Targeted Theranostics. AB - Targeted therapy has become an effective strategy of precision medicine for cancer treatment. Based on the success of antibody-drug conjugates (ADCs), here we report a theranostic design of small-molecule drug conjugates (T-SMDCs) for targeted imaging and chemotherapy of prostate cancer. The structure of T-SMDCs built upon a polyethylene glycol (PEG) scaffold consists of (i) a chelating moiety for positron emission tomography (PET) imaging when labeled with (68)Ga, a positron-emitting radioisotope; (ii) a prostate specific membrane antigen (PSMA) specific ligand for prostate cancer targeting; and (iii) a cytotoxic drug (DM1) for chemotherapy. For proof-of-concept, such a T-SMDC, NO3A-DM1-Lys-Urea-Glu, was synthesized and evaluated. The chemical modification of Lys-Urea-Glu for the construction of the conjugate did not compromise its specific binding affinity to PSMA. The PSMA-mediated internalization of (68)Ga-labeled NO3A-DM1-Lys-Urea-Glu displayed a time-dependent manner, allowing the desired drug delivery and release within tumor cells. The antiproliferative activity of the T-SMDC showed a positive correlation with the PSMA expression level. Small animal PET imaging with (68)Ga-labeled NO3A-DM1-Lys-Urea-Glu exhibited significantly higher uptake (p < 0.01) in the PSMA positive PC3-PIP tumors (4.30 +/- 0.20%ID/g) at 1 h postinjection than in the PSMA negative PC3-Flu tumors (1.12 +/- 0.42%ID/g). Taken together, we have successfully designed and synthesized a T-SMDC system for prostate cancer targeted imaging and therapy. PMID- 27248782 TI - C-C Bond Formation: Synthesis of C5 Substituted Pyrimidine and C8 Substituted Purine Nucleosides Using Water Soluble Pd-imidate Complex. AB - The synthesis of a highly efficient, water soluble [Pd(Sacc)2 (TPA)2 ] complex for C-C bond formation is described. Additionally, application of the [Pd(Sacc)2 (TPA)2 ] complex for Suzuki-Miyaura arylation of all four nucleosides (5-iodo-2' deoxyuridine [5-IdU], 5-iodo-2'-deoxycytidine [5-IdC], 8-bromo-2'-deoxyadenosine, and 8-bromo-2'-deoxyguanosine) with various aryl/heteroaryl boronic acids in plain water under milder conditions is demonstrated. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248783 TI - Simple, High-Yield Syntheses of DNA Duplexes Containing Interstrand DNA-DNA Cross Links Between an N(4) -Aminocytidine Residue and an Abasic Site. AB - The protocol describes the preparation and purification of interstrand DNA-DNA cross-links derived from the reaction of an N(4) -aminocytidine residue with an abasic site in duplex DNA. The procedures employ inexpensive, commercially available chemicals and enzymes to carry out post-synthetic modification of commercially available oligodeoxynucleotides. The yield of cross-linked duplex is typically better than 90%. If purification is required, the cross-linked duplex can be readily separated from single-stranded DNA starting materials by denaturing gel electrophoresis. The resulting covalent hydrazone-based cross links are stable under physiologically relevant conditions and may be useful for biophysical studies, structural analyses, DNA repair studies, and materials science applications. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248785 TI - Pre-Steady-State Kinetic Analysis of Single-Nucleotide Incorporation by DNA Polymerases. AB - Pre-steady-state kinetic analysis is a powerful and widely used method to obtain multiple kinetic parameters. This protocol provides a step-by-step procedure for pre-steady-state kinetic analysis of single-nucleotide incorporation by a DNA polymerase. It describes the experimental details of DNA substrate annealing, reaction mixture preparation, handling of the RQF-3 rapid quench-flow instrument, denaturing polyacrylamide DNA gel preparation, electrophoresis, quantitation, and data analysis. The core and unique part of this protocol is the rationale for preparation of the reaction mixture (the ratio of the polymerase to the DNA substrate) and methods for conducting pre-steady-state assays on an RQF-3 rapid quench-flow instrument, as well as data interpretation after analysis. In addition, the methods for the DNA substrate annealing and DNA polyacrylamide gel preparation, electrophoresis, quantitation and analysis are suitable for use in other studies. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248784 TI - Diffraction Techniques in Structural Biology. AB - A detailed understanding of chemical and biological function and the mechanisms underlying the molecular activities ultimately requires atomic-resolution structural data. Diffraction-based techniques such as single-crystal X-ray crystallography, electron microscopy, and neutron diffraction are well established and they have paved the road to the stunning successes of modern-day structural biology. The major advances achieved in the last twenty years in all aspects of structural research, including sample preparation, crystallization, the construction of synchrotron and spallation sources, phasing approaches, and high-speed computing and visualization, now provide specialists and nonspecialists alike with a steady flow of molecular images of unprecedented detail. The present unit combines a general overview of diffraction methods with a detailed description of the process of a single-crystal X-ray structure determination experiment, from chemical synthesis or expression to phasing and refinement, analysis, and quality control. For novices it may serve as a stepping stone to more in-depth treatises of the individual topics. Readers relying on structural information for interpreting functional data may find it a useful consumer guide. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248786 TI - Selection of Natural and Base-Modified DNA Aptamers for a Camptothecin Derivative. AB - Nucleic acid aptamers for small molecules are currently being developed and have a potential role in diverse applications including biosensing, diagnostics, and therapeutics involving low-molecular-weight biomarkers and drugs. To enhance and broaden their functions through chemical modification, systematic evolution of ligands by exponential enrichment (SELEX) selection has been attempted with modified DNA/RNA libraries. Recently, we demonstrated the superior efficacy of base modification for affinity enhancement and the usefulness of unnatural nucleic acid libraries for development of small-molecule aptamers. In this unit, we describe construction of a modified DNA library that includes (E)-5-(2-(N-(2 (N(6) -adeninyl)ethyl))carbamylvinyl)uracil bases and acquisition of high affinity camptothecin-binding DNA aptamers, in addition to those of the corresponding natural DNA library and aptamers, using the SELEX method. (c) 2016 by John Wiley & Sons, Inc. PMID- 27248787 TI - Copper thiocyanate: polytypes, defects, impurities, and surfaces. AB - Copper thiocyanate (CuSCN) is an established solid state dye in solar cells and has emerged as a key material for applications in transparent conductors and solution-processed thin film transistors. Here we report the results of density functional theory calculations on several fundamental properties related to the performance of CuSCN in the above-mentioned systems. We describe the structural and electronic properties of CuSCN phases and show that the material is prone to polytypism. We also perform a systematic study on various defects and hydrogen impurities and determine their effect on the electronic properties of the host system, particularly with respect to doping. Finally, we show that non-polar surfaces have low formation energies, suggesting easy cleavage along certain directions. PMID- 27248788 TI - Mesenchymal Stem Cells from Human Extra Ocular Muscle Harbor Neuroectodermal Differentiation Potential. AB - Mesenchymal stem cells (MSC) have been proposed as suitable candidates for cell therapy for neurological disorderssince they exhibit good neuronal differentiation capacity. However, for better therapeutic outcomes, it is necessary to isolate MSC from a suitable tissue sourcethat posses high neuronal differentiation. In this context, we isolated MSC from extra ocular muscle (EOM) tissue and tested the in vitro neuronal differentiation potential. In the current study, EOM tissue derived MSC were characterized and compared with bone marrow derived MSC. We found that EOM derived MSC proliferated as a monolayer and showed similarities in morphology, growth properties and cell surface marker expression with bone marrow derived MSC and expressed high levels of NES, OCT4, NANOG and SOX2 in its undifferentiated state. They also expressed embryonic cell surface marker SSEA4 and their intracellular mitochondrial distribution pattern was similar to that of multipotent stem cells. Although EOM derived MSC differentiated readily into adipocytes, osteocytes and chondrocytes, they differentiated more efficiently into neuroectodermal cells. The differentiation into neuroectodermal cellswas confirmed by the expression of neuronal markers NGFR and MAP2B. Thus, EOM derived MSC might be good candidates for stem cell based therapies for treating neurodegenerative diseases. PMID- 27248789 TI - Transitions of care in the management of acute bacterial skin and skin structure infections: a paradigm shift. AB - Acute bacterial skin and skin structure infections (ABSSSI) have evolved over a relatively short period of time to become one of the most challenging medical problems encountered in clinical practice. Notably the high incidence of methicillin-resistant S. aureus (MRSA) across the continuum of care has coincided with increased outpatient failures and higher rates of hospital admissions for parental antibiotic therapy. Consequently the management of ABSSSI constitutes a tremendous burden to the healthcare system in terms of cost of care and consumption of institutional and clinical resources. This perspective piece discusses current and new approaches to the management of ABSSSI in a hospital setting and the need for a multifaceted approach. Treatment strategies for the management through the utilization of observation units (OU), Outpatient Parental Antibiotic Therapy (OPAT), and newly developed antibiotics for the use against skin infections caused by Gram-positive bacteria will be discussed in the context of ABSSSI. PMID- 27248796 TI - Early experiences with tachycardia-triggered vagus nerve stimulation using the AspireSR stimulator. AB - Many epilepsy patients treated with vagus nerve stimulation additionally use an "on-demand" function, triggering an extra stimulation to terminate a seizure or diminish its severity. Nevertheless, a substantial number of patients are not able to actively trigger stimulations by use of a magnet, due to the absence of an aura or inability for voluntary actions in the early phase of a seizure. To address this need, a novel implantable pulse generator, the AspireSR VNS system, was developed to provide automated ictal stimulation triggered by a seizure detecting algorithm. We report our experience with three patients in assessing the functionality of ictal stimulation, illustrating the detection system in practice. Detection of ictal tachycardia and variable additional detections of physiological tachycardia depended on the individual seizure-detecting algorithm settings. PMID- 27248797 TI - Ebstein's Anomaly of the Tricuspid Valve in the Fetus - A Multicenter Experience. AB - Purpose To assess the spectrum of associated anomalies, the intrauterine course, the outcome and possible prognostic markers in prenatally diagnosed Ebstein's anomaly (EA). Materials and Methods All cases of EA diagnosed over a period of 13 years with a minimum follow-up of 1 year were retrospectively collected in 4 tertiary referral centers in Germany. Results In the study period 76 cases of EA were prenatally diagnosed. The mean gestational age at diagnosis was 25.0 weeks (range: 13 - 35). 41 (53.9 %) cases were isolated and 35 (46.1 %) had other cardiac and/or extracardiac anomalies. 19 (25.0 %) pregnant women opted for termination of pregnancy, intrauterine fetal death occurred in 7 cases (9.2 %), neonatal death in 14 cases (18.4 %), death in infancy or childhood in 9 cases (11.8 %) and 27 children (35.5 %) were alive at the last follow-up. After exclusion of terminations, the only parameter inversely correlated with intrauterine survival was hydrops fetalis. Prognostic parameters significantly associated with postnatal non-survival were an abnormal Celermajer index (right atrium/heart ratio > 0.7), cardiomegaly (cardiothoracic circumference ratio > 0.5), absence of antegrade flow over the pulmonary valve and earlier diagnosis in pregnancy. Conclusion Prenatally diagnosed EA has a high morbidity and mortality with the highest loss rate in the intrauterine and neonatal period. In our study, hydrops fetalis was the only parameter significantly associated with intrauterine demise, while other prenatal markers were only significantly associated with postnatal mortality. PMID- 27248799 TI - The exercise intensity at maximal oxygen uptake (i?O2max): Methodological issues and repeatability. AB - The minimum exercise intensity that elicits ?O2max (i?O2max) is an important variable associated with endurance exercise performance. i?O2max is usually determined during a maximal incremental exercise test; however, the magnitude and duration of the increments used influence the i?O2max value produced by a given test. The aims of this study were twofold. The first was to investigate whether the i?O2max value produced by a single cycle ergometer test (i?O2max(S)) was repeatable. The second was to determine if i?O2max(S) represents the minimum intensity at which ?O2max is elicited when compared to a refined i?O2max value (i?O2max(R)) derived from repeated tests. Seventeen male cyclists (age 33.9 +/- 7.7 years, body mass 80.9 +/- 10.2 kg, height 1.82 +/- 0.05 m; VO2max 4.27 +/- 0.62 L min(-1)) performed four maximal incremental tests for the determination of i?O2max(S) and i?O2max(R) (3 min stages; 20 W increments). Trials 1 and 2 were identical and used for assessing the repeatability of i?O2max(S), trials 3 and 4 began at different intensities and were used to determine i?O2max(R). i?O2max(S) showed good test-retest repeatability for i?O2max (CV = 4.1%; ICC = 0.93), VO2max (CV = 6.3%; ICC = 0.88) and test duration (CV = 6.7%; ICC = 0.89). There was no significant difference between i?O2max(S) and i?O2max(R) (303 +/- 40 W vs. 301 +/ 42 W) (P < .05). The present results suggest that i?O2max determined directly during a maximal incremental test is repeatable and provides a very good estimate of the minimum exercise intensity that elicits ?O2max. PMID- 27248800 TI - ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation. AB - In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID- 27248803 TI - Grazing Incidence Cross-Sectioning of Thin-Film Solar Cells via Cryogenic Focused Ion Beam: A Case Study on CIGSe. AB - Cryogenic focused ion beam (Cryo-FIB) milling at near-grazing angles is employed to fabricate cross-sections on thin Cu(In,Ga)Se2 with >8x expansion in thickness. Kelvin probe force microscopy (KPFM) on sloped cross sections showed reduction in grain boundaries potential deeper into the film. Cryo Fib-KPFM enabled the first determination of the electronic structure of the Mo/CIGSe back contact, where a sub 100 nm thick MoSey assists hole extraction due to 45 meV higher work function. This demonstrates that CryoFIB-KPFM combination can reveal new targets of opportunity for improvement in thin-films photovoltaics such as high-work function contacts to facilitate hole extraction through the back interface of CIGS. PMID- 27248802 TI - Structure and evolutionary history of a large family of NLR proteins in the zebrafish. AB - Multicellular eukaryotes have evolved a range of mechanisms for immune recognition. A widespread family involved in innate immunity are the NACHT-domain and leucine-rich-repeat-containing (NLR) proteins. Mammals have small numbers of NLR proteins, whereas in some species, mostly those without adaptive immune systems, NLRs have expanded into very large families. We describe a family of nearly 400 NLR proteins encoded in the zebrafish genome. The proteins share a defining overall structure, which arose in fishes after a fusion of the core NLR domains with a B30.2 domain, but can be subdivided into four groups based on their NACHT domains. Gene conversion acting differentially on the NACHT and B30.2 domains has shaped the family and created the groups. Evidence of positive selection in the B30.2 domain indicates that this domain rather than the leucine rich repeats acts as the pathogen recognition module. In an unusual chromosomal organization, the majority of the genes are located on one chromosome arm, interspersed with other large multigene families, including a new family encoding zinc-finger proteins. The NLR-B30.2 proteins represent a new family with diversity in the specific recognition module that is present in fishes in spite of the parallel existence of an adaptive immune system. PMID- 27248804 TI - Solid-Phase Synthetic Strategies for the Preparation of Purine Derivatives. AB - This Review summarizes all of the currently described strategies applicable for the solid-phase synthesis of purine derivatives. The individual approaches are classified according to the immobilization procedure used resulting in a linkage of the final scaffold at various positions. PMID- 27248801 TI - Modulation of cellular redox homeostasis by the endocannabinoid system. AB - The endocannabinoid system (ECS) and reactive oxygen species (ROS) constitute two key cellular signalling systems that participate in the modulation of diverse cellular functions. Importantly, growing evidence suggests that cross-talk between these two prominent signalling systems acts to modulate functionality of the ECS as well as redox homeostasis in different cell types. Herein, we review and discuss evidence pertaining to ECS-induced regulation of ROS generating and scavenging mechanisms, as well as highlighting emerging work that supports redox modulation of ECS function. Functionally, the studies outlined reveal that interactions between the ECS and ROS signalling systems can be both stimulatory and inhibitory in nature, depending on cell stimulus, the source of ROS species and cell context. Importantly, such cross-talk may act to maintain cell function, whereas abnormalities in either system may propagate and undermine the stability of both systems, thereby contributing to various pathologies associated with their dysregulation. PMID- 27248805 TI - Procedural and clinical outcomes of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy. AB - OBJECTIVE: The role of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy. DESIGN: Single-centre, retrospective cohort study. PATIENTS AND MEASUREMENTS: Medical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard. RESULTS: Biopsy was performed in 418 patients [62% men, median age 69 years (range, 15-91)] on 419 adrenal lesions, median size 3.1 cm (range, 0.6-24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra-adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity <=10 HU (42/137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88.5%, specificity of 91.5%, positive predictive value of 93.4% and negative predictive value of 85.5%. CONCLUSION: When used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemical testing for pheochromocytoma prior to adrenal biopsy are needed. PMID- 27248816 TI - A GCN2-Like eIF2alpha Kinase (LdeK1) of Leishmania donovani and Its Possible Role in Stress Response. AB - Translation regulation in Leishmania parasites assumes significance particularly because they encounter myriad of stresses during their life cycle. The eukaryotic initiation factor 2alpha (eIF2alpha) kinases, the well-known regulators of translation initiation in higher eukaryotes have now been found to control various processes in these protozoan parasites as well. Here, we report on cloning and characterization of a GCN2-like eIF2alpha kinase from L. donovani and also on its modulation during nutrient starvation. We cloned a GCN2-like kinase from L. donovani, which we named as LdeK1 and validated it to be a functional eIF2alpha kinase by in vitro kinase assay. LdeK1 was found to be localized in the cytoplasm of the promastigotes with a five-fold higher expression in this stage of the parasite as compared to the axenic amastigotes. Phosphorylation of eIF2alpha and a G1-arrest was observed in response to nutrient starvation in the wild-type parasites. In contrast, phosphorylation was significantly impaired in a dominant-negative mutant of LdeK1 during this stress with a subsequent failure to bring about a G1-arrest during cell cycle. Thus, LdeK1 is a functional GCN2-like kinase of L. donovani which responds to nutrient starvation by phosphorylating its substrate, eIF2alpha and a G1-arrest in the cell cycle. Nutrient starvation is encountered by the parasites inside the vector which triggers metacyclogenesis. We therefore propose that global translational regulation by activation of LdeK1 followed by eIF2alpha phosphorylation and G1-arrest during nutrient starvation in the gut of sandfly vector could be one of the mechanisms to retool the cellular machinery required for metacyclogenesis of Leishmania promastigotes. PMID- 27248817 TI - Growth of Catalyst-Free Epitaxial InAs Nanowires on Si Wafers Using Metallic Masks. AB - Development of heteroepitaxy growth of catalyst-free vertical III-V nanowires on Si wafers is highly desirable for future nanoscale Si-based electronic and optoelectronic devices. In this study, a proof-of-concept approach is developed for catalyst-free heteroepitaxy growth of InAs nanowires on Si wafers. Before the growth of InAs nanowires, a Si-compatible metallic film with a thickness of several tens of nanometers was predeposited on a Si wafer and then annealed to form nanosize openings so as to obtain a metallic mask. These nano-openings exposed the surface of the Si wafer, which allowed subsequent nucleation and growth of epitaxial InAs nanowires directly on the surface of the Si wafer. The small size of the nano-openings limits the lateral growth of the nanostructures but promotes their axial growth. Through this approach, catalyst-free InAs nanowires were grown on both Si (111) and (001) wafers successfully at different growth temperatures. In particular, ultralong defect-free InAs nanowires with the wurtzite structure were grown the Si (111) wafers at 550 degrees C using the Ni mask. This study offers a simple, cost-effective, and scalable method to grow catalyst-free III-V nanowires on Si wafers. The simplicity of the approach opens a new avenue for the growth and integration of catalyst-free high-quality heteroepitaxial III-V nanowires on Si wafers. PMID- 27248818 TI - Comparison of Respondent Driven Sampling Estimators to Determine HIV Prevalence and Population Characteristics among Men Who Have Sex with Men in Moscow, Russia. AB - Analytically distinct estimators have been proposed for the calculation of population-based estimates derived from respondent-driven sampling (RDS), yet there have been few comparisons of the inferences from these estimators using empirical data. We compared estimates produced by unweighted analysis used to calculate sample proportions and by three available estimators that are used to calculate population proportions, RDS-I, RDS-II (Volz-Heckathorn), and Gile's RDS SS. Data were derived from a cross-sectional, RDS study of men who have sex with men (MSM) conducted from October 2010 to April 2013 in Moscow, Russia (N = 1,376, recruitment depth: 31 waves). Analyses investigated the influence of key parameters: recruitment depth, homophily, and network size on sample and population estimates. Variability in results produced by the estimators and recruitment depth were statistically compared using the coefficient of variation (CV). Sample proportions had the least variability across different recruitment depths, compared to the RDS estimators. Population estimates tended to differ at lower recruitment depth but were approximately equal after reaching sampling equilibrium, highlighting the importance of sampling to greater recruitment depth. All estimators incorporate inverse probability weighting using self reported network size, explaining the similarities in across population estimates and the difference of these estimates relative to sample proportions. Current biases and limitations associated with RDS estimators are discussed. PMID- 27248819 TI - Targeted next-generation sequencing of dedifferentiated chondrosarcoma in the skull base reveals combined TP53 and PTEN mutations with increased proliferation index, an implication for pathogenesis. AB - Dedifferentiated chondrosarcoma (DDCS) is a rare disease with a dismal prognosis. DDCS consists of two morphologically distinct components: the cartilaginous and noncartilaginous components. Whether the two components originate from the same progenitor cells has been controversial. Recurrent DDCS commonly displays increased proliferation compared with the primary tumor. However, there is no conclusive explanation for this mechanism. In this paper, we present two DDCSs in the sellar region. Patient 1 exclusively exhibited a noncartilaginous component with a TP53 frameshift mutation in the pathological specimens from the first surgery. The tumor recurred after radiation therapy with an exceedingly increased proliferation index. Targeted next-generation sequencing (NGS) revealed the presence of both a TP53 mutation and a PTEN deletion in the cartilaginous and the noncartilaginous components of the recurrent tumor. Fluorescence in situ hybridization and immunostaining confirmed reduced DNA copy number and protein levels of the PTEN gene as a result of the PTEN deletion. Patient 2 exhibited both cartilaginous and noncartilaginous components in the surgical specimens. Targeted NGS of cells from both components showed neither TP53 nor PTEN mutations, making Patient 2 a naive TP53 and PTEN control for comparison. In conclusion, additional PTEN loss in the background of the TP53 mutation could be the cause of increased proliferation capacity in the recurrent tumor. PMID- 27248820 TI - Pellino-1 confers chemoresistance in lung cancer cells by upregulating cIAP2 through Lys63-mediated polyubiquitination. AB - Pellino-1 is an E3 ubiquitin ligase that mediates immune receptor signaling pathways. The role of Pellino-1 in oncogenesis of lung cancer was investigated in this study. Pellino-1 expression was increased in human lung cancer cell lines compared with non-neoplastic lung cell lines. Pellino-1 overexpression in human lung cancer cells, A549 and H1299 cells, increased the survival and colony forming ability. Pellino-1 overexpression in these cells also conferred resistance to cisplatin- or paclitaxel-induced apoptosis. In contrast, depletion of Pellino-1 decreased the survival of A549 and H1299 cells and sensitized these cells to cisplatin- and paclitaxel-induced apoptosis. Pellino-1 overexpression in A549 and H1299 cells upregulated the expression of inhibitor of apoptosis (IAP) proteins, including cIAP1 and cIAP2, while Pellino-1 depletion downregulated these molecules. Notably, Pellino-1 directly interacted with cIAP2 and stabilized cIAP2 through lysine63-mediated polyubiquitination via its E3 ligase activity. Pellino-1-mediated chemoresistance in lung cancer cells was dependent on the induction of cIAP2. Moreover, a strong positive correlation between Pellino-1 and the cIAP2 expression was observed in human lung adenocarcinoma tissues. Taken together, these results demonstrate that Pellino-1 contributes to lung oncogenesis through the overexpression of cIAP2 and promotion of cell survival and chemoresistance. Pellino-1 might be a novel oncogene and potential therapeutic target in lung cancer. PMID- 27248821 TI - Inhibition of ALK1 signaling with dalantercept combined with VEGFR TKI leads to tumor stasis in renal cell carcinoma. AB - Treatment of metastatic renal cell carcinoma (mRCC) with agents that block signaling through vascular endothelial growth factor receptor 2 (VEGFR2) induces disease regression or stabilization in some patients; however, these responses tend to be short-lived. Therefore, development of combination therapies that can extend the efficacy of VEGFR antagonists in mRCC remains a priority.We studied murine xenograft models of RCC that become refractory to treatment with the VEGFR tyrosine kinase inhibitor (TKI) sunitinib. Dalantercept is a novel antagonist of Activin receptor-like kinase 1 (ALK1)/Bone morphogenetic protein (BMP) 9 signaling. Dalantercept inhibited growth in the murine A498 xenograft model which correlated with hyperdilation of the tumor vasculature and an increase in tumor hypoxia. When combined with sunitinib, dalantercept induced tumor necrosis and prevented tumor regrowth and revascularization typically seen with sunitinib monotherapy in two RCC models. Combination therapy led to significant downregulation of angiogenic genes as well as downregulation of endothelial specific gene expression particularly of the Notch signaling pathway. We demonstrate that simultaneous targeting of molecules that control distinct phases of angiogenesis, such as ALK1 and VEGFR, is a valid strategy for treatment of mRCC. At the molecular level, combination therapy leads to downregulation of Notch signaling. PMID- 27248822 TI - Viral oncomiR spreading between B and T cells is employed by Kaposi's sarcoma herpesvirus to induce non-cell-autonomous target gene regulation. AB - The two human lymphotrophic gamma-herpesviruses, Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV), are a recognized cause of human cancer, encoding multiple miRs that are major players in carcinogenesis. Previously, we discovered that EBV-encoded miRs transfer between infected B and T lymphocytes. To further explore the biological significance of the spreading of gamma herpesvirus-encoded miRs on carcinogenesis, we focused on KSHV-miR-K12-11 (miR K12-11) that is unique in having an identical seed sequence with the oncomiR hsa miR-155, implicated in B cell lymphomas development. Here, we show for the first time that miR-K12-11 transfers in vitro from KSHV-infected BCBL-1 and BC-1 lymphoma lines to T cells. The transferred miR-K12-11 is active in the adopting T cells and binds its canonical target, the 3'-UTR of BACH1. Importantly, we show that the transfer of miR-K12-11 from BCBL-1 to Jurkat cells correlates with inhibition of the innate type-I interferons response to viral dsRNAs downstream of IKKepsilon, a validated miR-K12-11 target. Finally, we show that miR-K12-11 spreading is not reduced by blocking the classical ceramide-dependent exosome secretion pathway. In summary, we report for the first time that intercellular viral oncomiR spreading is an additional mechanism employed by KSHV to inhibit host anti-viral immunity and consequently promote oncogenesis. PMID- 27248823 TI - TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis. AB - Colorectal carcinoma (CRC) is a malignant epithelial tumour with tremendous invasion and metastatic capacity. Transforming acidic coiled-coil protein-3 (TACC3), a frequently aberrantly expressed oncogene, is an important biomarker in various human cancers. Our study aimed to investigate the expression and function of TACC3 in human CRC. We found that TACC3 was over-expressed at both the mRNA and protein levels in CRC cells and in biopsies of CRC tissues compared with normal controls as determined by qRT-PCR, western blot and immunohistochemical (IHC) staining assays. IHC staining of samples from 161 patients with CRC also revealed that TACC3 expression was significantly correlated with clinical stage (P = 0.045), T classification (P = 0.029) and M classification (P = 0.020). Multivariate analysis indicated that high TACC3 expression was an independent prognostic marker for CRC. Patients who had high TACC3 expression had significantly poorer overall survival (OS, P = 0.023) and disease-free survival (DFS, P = 0.019) compared to patients who had low TACC3 expression. Furthermore, TACC3 knockdown attenuated CRC cell proliferation, colony formation capability, migration and invasion capability, and tumourigenesis in nude mice; these properties were measured using a real-time cell analyser (RTCA), clonogenicity analysis, and transwell and xenograft assays, respectively. These data indicate that TACC3 promotes CRC progression and could be an independent prognostic factor and a potential therapeutic target for CRC. PMID- 27248824 TI - Phospholipid scramblase 1 as a critical node at the crossroad between autophagy and apoptosis in mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is an aggressive haematological malignancy in which the response to therapy can be limited by aberrantly activated molecular and cellular pathways, among which autophagy was recently listed. Our study shows that the 9-cis-retinoic acid (RA)/Interferon(IFN)-alpha combination induces protective autophagy in MCL cell lines and primary cultures reducing the extent of drug-induced apoptosis. The treatment significantly up-regulates phospholipid scramblase 1 (PLSCR1), a protein which bi-directionally flips lipids across membranes. In particular, RA/IFN-alpha combination concomitantly increases PLSCR1 transcription and controls PLSCR1 protein levels via lysosomal degradation. Herein we describe a new function for PLSCR1 as negative regulator of autophagy. Indeed, PLSCR1 overexpression reduced MCL cell susceptibility to autophagy induced by RA/IFN-alpha, serum deprivation or mTOR pharmacological inhibition. Moreover, PLSCR1 can bind the ATG12/ATG5 complex preventing ATG16L1 recruitment and its full activation, as indicated by co-immunoprecipitation experiments. The combination of doxorubicin or bortezomib with RA/IFN-alpha strengthened PLSCR1 up regulation and enhanced apoptosis, as a likely consequence of the blockade of RA/IFN-alpha-induced autophagy. Immunohistochemical analysis of 32 MCL biopsies revealed heterogeneous expression of PLSCR1 and suggests its possible implication in the response to anticancer therapies, especially to drugs promoting protective autophagy. PMID- 27248825 TI - Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer. AB - Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown.Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC).Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-beta or alpha-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-alpha and -beta and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-alpha and -beta remained independent factors for survival in multivariate analyses.Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-alpha and -beta were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections. PMID- 27248826 TI - The inflammatory/cancer-related IL-6/STAT3/NF-kappaB positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts. AB - The IL-6/STAT3/NF-kappaB positive feedback loop links inflammation to cancer and maintains cells at a transformed state. Similarly, cancer-associated myofibroblats remains active even in absence of cancer cells. However, the molecular basis of this sustained active state remains elusive. We have shown here that breast cancer cells and IL-6 persistently activate breast stromal fibroblasts through the stimulation of the positive IL-6/STAT3/NF-kappaB feedback loop. Transient neutralization of IL-6 in culture inhibited this signaling circuit and reverted myofibrobalsts to a normalized state, suggesting the implication of the IL-6 autocrine feedback loop as well. Importantly, the IL 6/STAT3/NF-kappaB pro-inflammatory circuit was also active in cancer-associated fibroblasts isolated from breast cancer patients. Transient inhibition of STAT3 by specific siRNA in active fibroblasts persistently reduced the level of the RNA binding protein AUF1, blocked the loop and normalized these cells. Moreover, we present clear evidence that AUF1 is also part of this positive feedback loop. Interestingly, treatment of breast myofibroblasts with caffeine, which has been previously shown to persistently inhibit active breast stromal fibroblasts, blocked the positive feedback loop through potent and sustained inhibition of STAT3, AKT, lin28B and AUF1. These results indicate that the IL-6/STAT3/NF-kappaB positive feedback loop includes AUF1 and is responsible for the sustained active status of cancer-associated fibroblasts. We have also shown that normalizing myofibroblasts, which could be of great therapeutic value, is possible through the inhibition of this procarcinogenic circuit. PMID- 27248827 TI - Validation study for the hypothesis of internal mammary sentinel lymph node lymphatic drainage in breast cancer. AB - According to axilla sentinel lymph node lymphatic drainage pattern, we hypothesized that internal mammary sentinel lymph node (IM-SLN) receives lymphatic drainage from not only the primary tumor area, but also the entire breast parenchyma. Based on the hypothesis a modified radiotracer injection technique was established and could increase the visualization rate of the IM-SLN significantly. To verify the hypothesis, two kinds of tracers were injected at different sites of breast. The radiotracer was injected with the modified technique, and the fluorescence tracer was injected in the peritumoral intra parenchyma. The location of IM-SLN was identified by preoperative lymphoscintigraphy and intraoperative gamma probe. Then, internal mammary sentinel lymph node biopsy (IM-SLNB) was performed. The fluorescence status of IM SLN was identified by the fluorescence imaging system. A total of 216 patients were enrolled from September 2013 to July 2015. The overall visualization rate of IM-SLN was 71.8% (155/216). The success rate of IM-SLNB was 97.3% (145/149). The radiotracer and the fluorescence tracer were identified in the same IM-SLN in 127 cases, the correlation and the agreement is significant (Case-base, rs=0.836, P<0.001; Kappa=0.823, P<0.001). Different tracers injected into the different sites of the intra-parenchyma reached the same IM-SLN, which demonstrates the hypothesis that IM-SLN receives the lymphatic drainage from not only the primary tumor area but also the entire breast parenchyma. PMID- 27248829 TI - Tetranuclear Zn/4f coordination clusters as highly efficient catalysts for Friedel-Crafts alkylation. AB - A series of custom-designed, high yield, isoskeletal tetranuclear Zn/4f coordination clusters showing high efficiency as catalysts with low catalytic loadings in Friedel-Crafts alkylation are described for the first time. The possibility of altering the 4f centers in these catalysts without altering the core topology allows us to further confirm their stability via EPR and NMR, as well to gain insights into the plausible reaction mechanism, showcasing the usefulness of these bimetallic systems as catalysts. PMID- 27248828 TI - Long noncoding RNA CPS1-IT1 suppresses the metastasis of hepatocellular carcinoma by regulating HIF-1alpha activity and inhibiting epithelial-mesenchymal transition. AB - Recently, increasing numbers of long noncoding RNAs (lncRNAs), with both oncogenic and tumor-suppressive potential, have been found to be aberrantly expressed in various human cancers. However, the function of lncRNAs in hepatocellular carcinoma (HCC) progression remains largely unknown. In this study, we performed a comprehensive microarray analysis of lncRNA expression using human HCC specimens. After validation in 119 human HCC tissues, we identified a novel tumor suppressor lncRNA, CPS1 intronic transcript 1 (CPS1 IT1). To elucidate the clinical significance of CPS1-IT1 in HCC, correlations between CPS1-IT1 levels, clinical parameters, and survival outcomes were analyzed. In vitro and in vivo functional assays were also performed to dissect the potential underlying mechanisms. Expression of CPS1-IT1 was significantly decreased in 73% of HCC tissues, and patients with low CPS1-IT1 expression had poor survival outcomes. Furthermore, in vitro functional assays indicated that CPS1-IT1 significantly reduced cell proliferation, migration and invasion capacities through reduced Hsp90 binding to and activation of HIF-1alpha, thereby suppressing the epithelial-mesenchymal transition (EMT). An in vivo animal model also demonstrated the tumor suppressor role of CPS1- IT1 via decreased tumor growth and metastasis. In conclusion, lncRNA CPS1-IT1 acts as a tumor suppressor in HCC by reducing HIF-1alpha activation and suppressing EMT. The findings of this study establish a function for CPS1-IT1 in HCC progression and suggest its potential as a new prognostic biomarker and target for HCC therapy. PMID- 27248830 TI - Impacts of Climate Change on the Global Invasion Potential of the African Clawed Frog Xenopus laevis. AB - By altering or eliminating delicate ecological relationships, non-indigenous species are considered a major threat to biodiversity, as well as a driver of environmental change. Global climate change affects ecosystems and ecological communities, leading to changes in the phenology, geographic ranges, or population abundance of several species. Thus, predicting the impacts of global climate change on the current and future distribution of invasive species is an important subject in macroecological studies. The African clawed frog (Xenopus laevis), native to South Africa, possesses a strong invasion potential and populations have become established in numerous countries across four continents. The global invasion potential of X. laevis was assessed using correlative species distribution models (SDMs). SDMs were computed based on a comprehensive set of occurrence records covering South Africa, North America, South America and Europe and a set of nine environmental predictors. Models were built using both a maximum entropy model and an ensemble approach integrating eight algorithms. The future occurrence probabilities for X. laevis were subsequently computed using bioclimatic variables for 2070 following four different IPCC scenarios. Despite minor differences between the statistical approaches, both SDMs predict the future potential distribution of X. laevis, on a global scale, to decrease across all climate change scenarios. On a continental scale, both SDMs predict decreasing potential distributions in the species' native range in South Africa, as well as in the invaded areas in North and South America, and in Australia where the species has not been introduced. In contrast, both SDMs predict the potential range size to expand in Europe. Our results suggest that all probability classes will be equally affected by climate change. New regional conditions may promote new invasions or the spread of established invasive populations, especially in France and Great Britain. PMID- 27248831 TI - Some Behaviorial Science Measurement Concerns and Proposals. AB - Primarily from a measurement standpoint, we question some basic beliefs and procedures characterizing the scientific study of human behavior. The relations between observed and unobserved variables are key to an empirical approach to building explanatory theories and we are especially concerned about how the former are used as proxies for the latter. We believe that behavioral science can profitably reconsider the prevailing version of this arrangement because of its vulnerability to limiting idiosyncratic aspects of observed/unobserved variable relations. We describe a general measurement approach that takes into account idiosyncrasies that should be irrelevant to the measurement process but can intrude and may invalidate it in ways that distort and weaken relations among theoretically important variables. To clarify further our major concerns, we briefly describe one version of the measurement approach that fundamentally supports the individual as the primary unit of analysis orientation that we believe should be preeminent in the scientific study of human behavior. PMID- 27248832 TI - Resistive Switching in All-Oxide Ferroelectric Tunnel Junctions with Ionic Interfaces. AB - Universal, giant and nonvolatile resistive switching is demonstrated for oxide tunnel junctions with ferroelectric PbZr0.2 Ti0.8 O3 , ferroelectric BaTiO3, and paraelectric SrTiO3 tunnel barriers. The effects are caused by reversible migration of oxygen vacancies between the tunnel barrier and bottom La2/3 Sr1/3 MnO3 electrode. The switching process, which is driven by large electric fields, is efficient down to a temperature of 5 K. PMID- 27248833 TI - Identification of an anti-inflammatory potential of Eriodictyon angustifolium compounds in human gingival fibroblasts. AB - Polyphenol-rich plant extracts have been shown to possess anti-inflammatory activity against oral pathogen-induced cytokine release in model systems of inflammation. Here, it was hypothesized that a flavanone-rich extract of E. angustifolium exhibits an anti-inflammatory potential against endotoxin-induced inflammatory response in human gingival fibroblasts (HGF-1). HGF-1 cells were stimulated with lipopolysaccharide from Porphyromonas gingivalis (pg-LPS) to release pro-inflammatory cytokines. Concentrations of interleukins IL-6 and IL-8 and macrophage chemoattractant protein-1 in the incubation media upon stimulation were determined by means of magnetic bead analysis. A crude ethanol/water extract of E. angustifolium (EE) was fractionated via gel permeation chromatography into a flavanone-rich fraction (FF) and an erionic acid-rich fraction (EF). Individual flavanones and erionic acids as well as EE, EF and FF were tested in the pg-LPS stimulated HGF-1 cells for their anti-inflammatory potential. The E. angustifolium extract possessed anti-inflammatory potential in this model system, attenuating the pg-LPS-induced release of IL-6 by up to 52.0 +/- 15.5%. Of the individual flavanones, eriodictyol and naringenin had the most pronounced effect. However, a mixture of the flavanones did not possess the same effect as the entire flavanoid fraction, indicating that other compounds may contribute to the anti-inflammatory potential of E. angustifolium. For the first time, an anti inflammatory potential of E. angustifolium and containing erionic acids has been determined. PMID- 27248834 TI - Talk the Walk: Does Socio-Cognitive Resource Reallocation Facilitate the Development of Walking? AB - Walking is of interest to psychology, robotics, zoology, neuroscience and medicine. Human's ability to walk on two feet is considered to be one of the defining characteristics of hominoid evolution. Evolutionary science propses that it emerged in response to limited environmental resources; yet the processes supporting its emergence are not fully understood. Developmental psychology research suggests that walking elicits cognitive advancements. We postulate that the relationship between cognitive development and walking is a bi-directional one; and further suggest that the initiation of novel capacities, such as walking, is related to internal socio-cognitive resource reallocation. We shed light on these notions by exploring infants' cognitive and socio-communicative outputs prospectively from 6-18 months of age. Structured bi/tri weekly evaluations of symbolic and verbal development were employed in an urban cohort (N = 9) for 12 months, during the transition from crawling to walking. Results show links between preemptive cognitive changes in socio-communicative output, symbolic-cognitive tool-use processes, and the age of emergence of walking. Plots of use rates of lower symbolic play levels before and after emergence of new skills illustrate reductions in use of previously attained key behaviors prior to emergence of higher symbolic play, language and walking. Further, individual differences in age of walking initiation were strongly related to the degree of reductions in complexity of object-use (r = .832, p < .005), along with increases, counter to the general reduction trend, in skills that serve recruitment of external resources [socio-communication bids before speech (r = .696, p < .01), and speech bids before walking; r = .729, p < .01)]. Integration of these proactive changes using a computational approach yielded an even stronger link, underscoring internal resource reallocation as a facilitator of walking initiation (r = .901, p<0.001). These preliminary data suggest that representational capacities, symbolic object use, language and social developments, form an integrated adaptable composite, which possibly enables proactive internal resource reallocation, designed to support the emergence of new developmental milestones, such as walking. PMID- 27248835 TI - Ecosystem Alterations and Species Range Shifts: An Atlantic-Mediterranean Cephalaspidean Gastropod in an Inland Egyptian Lake. AB - The eastern Atlantic and Mediterranean marine Cephalaspidea gastropod Haminoea orbignyana was collected from Lake Qarun (Fayoum, Egypt), a landlocked lake that has undergone a shift from freshwater to estuarine conditions in the past 100 years. Species identity was confirmed by both morphological (anatomical dissection and scanning electron microscopy) and molecular methods (COI gene phylogeny). Observations suggested a robust population of H. orbignyana in the lake with a density of ca. 64 individuals/m2 and ca. 105 egg masses/m2 during surveys conducted in the summer of 2013. The vast majority of snails and egg masses were found under rocks. Observations of egg masses in the lab showed a gradual change from whitish to yellow-green as the eggs matured and the release of veliger larvae alone after about a week. Although adult cephalaspideans readily consumed filamentous red and green algae, and cyanobacteria, laboratory trials showed that they consumed significantly more of the red alga Ceramium sp., than of the green alga Cladophora glomerata, with consumption of Oscillatoria margaritifera being similar to those on the two algae. When grown on these resources for 16 days, H. orbignyana maintained their mass on the rhodophyte and cyanobacterium, but not in starvation controls. No cephalaspideans grew over the course of this experiment. Lake Qarun has been periodically restocked with Mediterranean fishes and prawns since the 1920s to maintain local fisheries, which represents a possible route of colonization for H. orbignyana. Yet, based on literature records, it seems more likely that invasion of the lake by this gastropod species has occurred only within the last 20 years. As human activities redistribute species through direct and indirect means, the structure of the community of this inland lake has become unpredictable and the long-term effects of these recent introductions are unknown. PMID- 27248836 TI - Cholinesterase inhibitor (Altenuene) from an endophytic fungus Alternaria alternata: optimization, purification and characterization. AB - AIMS: The aim of this study was to screen endophytic fungi isolated from Vinca rosea for their potential to produce acetylcholinesterase (AChE) inhibitors. METHOD AND RESULTS: Endophytic fungi isolated from V. rosea (Catharanthus roseus), were screened for AChE inhibitor production using Ellman's method. Maximum inhibition against AChE (78%) was observed in an isolate VS-10, identified to be Alternaria alternata on morphological and molecular basis. The isolate also inhibited butyrylcholinesterase (73%). Significant increase (1.3 fold) was achieved after optimization of process parameters using one variable at time approach. The inhibitor was purified using chromatographic techniques. The structure elucidation of the inhibitor was carried out using spectroscopic techniques and was identified to be 'altenuene'. The purified inhibitor possessed antioxidant potential as revealed by dot blot assay. The insecticidal potential of purified inhibitor was evaluated by feeding Spodoptora litura on diet amended with inhibitor. It evinced significant larval mortality. CONCLUSIONS: Endophytic A. alternata can serve as a source of dual cholinesterase inhibitor 'altenuene' with significant antioxidant and insecticidal activity. This is the first report on acetylcholinestearse inhibitory activity of altenuene. SIGNIFICANCE AND IMPACT OF THE STUDY: Alternaria alternata has the potential to produce a dual ChE inhibitor with antioxidant activity useful in the treatment of neurodegenerative disorders and in agriculture as biocontrol agent. PMID- 27248837 TI - Tachykinin-Related Peptides Share a G Protein-Coupled Receptor with Ion Transport Peptide-Like in the Silkworm Bombyx mori. AB - Recently, we identified an orphan Bombyx mori neuropeptide G protein-coupled receptor (BNGR)-A24 as an ion transport peptide-like (ITPL) receptor. BNGR-A24 belongs to the same clade as BNGR-A32 and -A33, which were recently identified as natalisin receptors. Since these three BNGRs share high similarities with known receptors for tachykinin-related peptides (TRPs), we examined whether these BNGRs can function as physiological receptors for five endogenous B. mori TRPs (TK-1 5). In a heterologous expression system, BNGR-A24 acted as a receptor for all five TRPs. In contrast, BNGR-A32 responded only to TK-5, and BNGR-A33 did not respond to any of the TRPs. These findings are consistent with recent studies on the ligand preferences for B. mori natalisins. Furthermore, we evaluated whether the binding of ITPL and TRPs to BNGR-A24 is competitive by using a Ca2+ imaging assay. Concomitant addition of a TRP receptor antagonist, spantide I, reduced the responses of BNGR-A24 not only to TK-4 but also to ITPL. The results of a binding assay using fluorescent-labeled BNGR-A24 and ligands demonstrated that the binding of ITPL to BNGR-A24 was inhibited by TK-4 as well as by spantide I, and vice versa. In addition, the ITPL-induced increase in cGMP levels of BNGR-A24 expressing BmN cells was suppressed by the addition of excess TK-4 or spantide I. The intracellular levels of cAMP and cGMP, as second messenger candidates of the TRP signaling, were not altered by the five TRPs, suggesting that these peptides act via different signaling pathways from cAMP and cGMP signaling at least in BmN cells. Taken together, the present findings suggest that ITPL and TRPs are endogenous orthosteric ligands of BNGR-A24 that may activate discrete signaling pathways. This receptor, which shares orthosteric ligands, may constitute an important model for studying ligand-biased signaling. PMID- 27248839 TI - Synergy between Two Metal Catalysts: A Highly Active Silica-Supported Bimetallic W/Zr Catalyst for Metathesis of n-Decane. AB - A well-defined, silica-supported bimetallic precatalyst [=Si-O-W(Me)5=Si-O Zr(Np)3] (4) has been synthesized for the first time by successively grafting two organometallic complexes [W(Me)6 (1) followed by ZrNp4 (2)] on a single silica support. Surprisingly, multiple-quantum NMR characterization demonstrates that W and Zr species are in close proximity to each other. Hydrogenation of this bimetallic catalyst at room temperature showed the easy formation of zirconium hydride, probably facilitated by tungsten hydride which was formed at this temperature. This bimetallic W/Zr hydride precatalyst proved to be more efficient (TON = 1436) than the monometallic W hydride (TON = 650) in the metathesis of n decane at 150 degrees C. This synergy between Zr and W suggests that the slow step of alkane metathesis is the C-H bond activation that occurs on Zr. The produced olefin resulting from a beta-H elimination undergoes easy metathesis on W. PMID- 27248838 TI - Effect of photodynamic therapy for the treatment of halitosis in adolescents - a controlled, microbiological, clinical trial. AB - Halitosis can exert a negative influence on the social relations of adolescents and affect one's self-image. The aim of this study was to evaluate the clinical and microbiological effect of antimicrobial photodynamic therapy (aPDT) on halitosis in adolescents. Forty-six individuals aged 12 to 19 years were randomly allocated: Group 1 - treatment with photodynamic therapy; Group 2 - treatment with a tongue scraper and Group 3 - treatment with a tongue scraper and photodynamic therapy. The count of bacterial colony-forming units per milliliter was used for the microbiological analysis. Statistical analysis involved the Kruskal-Wallis test followed by the Student-Newman-Keuls test. ANOVA was used for the determination of colony-forming units after treatment. The level of significance for all statistical tests was 5% (p < 0.05). After treatment, a statistically significant reduction in total volatile sulfur compounds was found in all groups (p < 0.001), with the largest reduction (median: 0) found in Group 3 (tongue scraper and photodynamic therapy). Moreover, a statistically significant difference was found between treatment with aPDT and a tongue scraper alone (p < 0.001). The present findings demonstrate an option for the treatment of halitosis in adolescents, with an immediate effect and without the mechanical aggression to the toungue. Clinical Trials: NCT02007993. PMID- 27248840 TI - Quality Assessment of Urinary Stone Analysis: Results of a Multicenter Study of Laboratories in Europe. AB - After stone removal, accurate analysis of urinary stone composition is the most crucial laboratory diagnostic procedure for the treatment and recurrence prevention in the stone-forming patient. The most common techniques for routine analysis of stones are infrared spectroscopy, X-ray diffraction and chemical analysis. The aim of the present study was to assess the quality of urinary stone analysis of laboratories in Europe. Nine laboratories from eight European countries participated in six quality control surveys for urinary calculi analyses of the Reference Institute for Bioanalytics, Bonn, Germany, between 2010 and 2014. Each participant received the same blinded test samples for stone analysis. A total of 24 samples, comprising pure substances and mixtures of two or three components, were analysed. The evaluation of the quality of the laboratory in the present study was based on the attainment of 75% of the maximum total points, i.e. 99 points. The methods of stone analysis used were infrared spectroscopy (n = 7), chemical analysis (n = 1) and X-ray diffraction (n = 1). In the present study only 56% of the laboratories, four using infrared spectroscopy and one using X-ray diffraction, fulfilled the quality requirements. According to the current standard, chemical analysis is considered to be insufficient for stone analysis, whereas infrared spectroscopy or X-ray diffraction is mandatory. However, the poor results of infrared spectroscopy highlight the importance of equipment, reference spectra and qualification of the staff for an accurate analysis of stone composition. Regular quality control is essential in carrying out routine stone analysis. PMID- 27248841 TI - Hydrolytic Activation Kinetics of the Herbicide Benzobicyclon in Simulated Aquatic Systems. AB - Herbicide resistance is a growing concern for weeds in California rice fields. Benzobicyclon (BZB; 3-(2-chloro-4-(methylsulfonyl)benzoyl)-2 phenylthiobicyclo[3.2.1]oct-2-en-4-one) has proven successful against resistant rice field weeds in Asia. A pro-herbicide, BZB forms the active agent, benzobicyclon hydrolysate (BH), in water; however, the transformation kinetics are not understood for aquatic systems, particularly flooded California rice fields. A quantitative experiment was performed to assess the primary mechanism and kinetics of BZB hydrolysis to BH. Complete conversion to BH was observed for all treatments. Basic conditions (pH 9) enhanced the reaction, with half-lives ranging from 5 to 28 h. Dissolved organic carbon (DOC) hindered transformation, which is consistent with other base-catalyzed hydrolysis reactions. BH was relatively hydrolytically stable, with 18% maximum loss after 5 days. Results indicate BZB is an efficient pro-herbicide under aqueous conditions such as those of a California rice field, although application may be best suited for fields with recirculating tailwater systems. PMID- 27248842 TI - Evaluation of Representations and Response Models for Polarizable Force Fields. AB - For classical simulations of condensed-phase systems, such as organic liquids and biomolecules, to achieve high accuracy, they will probably need to incorporate an accurate, efficient model of conformation-dependent electronic polarization. Thus, it is of interest to understand what determines the accuracy of a polarizable electrostatics model. This study approaches this problem by breaking polarization models down into two main components: the representation of electronic polarization and the response model used for mapping from an inducing field to the polarization within the chosen representation. Among the most common polarization representations are redistribution of atom-centered charges, such as those used in the fluctuating charge model, and atom-centered point dipoles, such as those used in a number of different polarization models. Each of these representations has been combined with one or more response models. The response model of fluctuating charge, for example, is based on the idea of electronegativity equalization in the context of changing electrostatic potentials (ESPs), whereas point-dipole representations typically use a response model based on point polarizabilities whose induced dipoles are computed based on interaction with other charges and dipoles. Here, we decouple polarization representations from their typical response models to analyze the strengths and weaknesses of various polarization approximations. First, we compare the maximal possible accuracies achievable by the charge redistribution and point-dipole model representations, by testing their ability to replicate quantum mechanical (QM) ESPs around small molecules polarized by external inducing charges. Perhaps not surprisingly, the atom-centered dipole model can yield higher accuracy. Next, we test two of the most commonly used response functions used for the point dipole representations, self-consistent and direct (or first-order) inducible point polarizabilities, where the polarizabilities are optimized to best fit the full set of polarized QM potentials for each molecule studied. Strikingly, the induced-dipole response model markedly degrades accuracy relative to that obtainable with optimal point dipoles. In fact, the maximal accuracy achievable with this response model is even lower than that afforded by an optimal charge redistribution representation. This means that, if coupled with a sufficiently accurate response function, the point-charge representation could outperform the standard induced-dipole model. Furthermore, although a key advantage of the point dipole representation, relative to charge redistribution, is its ability to capture out-of-plane polarization, the inducible dipole response model causes it to be less accurate than optimal charge redistribution for out-of-plane induction of the planar nitrobenzene molecule. Thus, the widely used inducible dipole response function falls short of the full potential accuracy achievable with the point-dipole representation it employs. Additional results reported here bear on the relative accuracy of self-consistent inducible dipoles versus that of the first-order, or direct, approximation and on methods for assigning partial atomic charges for use in conjunction with inducible dipole models. In sum, these results point to the improvement of polarization response models as an important direction for future research aimed at improving the accuracy of molecular simulations. PMID- 27248843 TI - Care staff training based on person-centered care and dementia care mapping, and its effects on the quality of life of nursing home residents with dementia. AB - OBJECTIVES: To assess the effects of care staff training based on person-centered care (PCC) and dementia care mapping (DCM) on the quality of life (QOL) of residents with dementia in a nursing home. METHODS: An intervention of staff training based on PCC and DCM was conducted with 40 care staff members at a geriatric nursing home. The effects of the staff training on the QOL of residents with dementia were evaluated by the DCM measurements of 40 residents with dementia three times at about one-month intervals (first, baseline; second, pre intervention; third, post-intervention). RESULTS: The well-being and ill-being values (WIB values) of the residents with dementia measured by DCM were not different between the first and second rounds before the staff training (p = 0.211). Meanwhile, the WIB values increased from the first and second rounds to the third post-intervention round (p = 0.035 and p < 0.001, respectively); over 50% of the residents had better WIB values. The behavior category 'interactions with others' in DCM also demonstrated a significant increase in the third round compared to the first round (p = 0.041). CONCLUSION: Staff training based on PCC and DCM could effectively improve the QOL of residents with dementia. PMID- 27248844 TI - Transcriptome profiling of patient derived xenograft models established from pediatric acute myeloid leukemia patients confirm maintenance of FLT3-ITD mutation. PMID- 27248845 TI - Oncologic outcomes of patients with positive margins after laser cordectomy for T1 and T2 glottic squamous cell carcinoma. AB - BACKGROUND: The oncologic impact of surgical margins after transoral laser microsurgery (TLM) for T1 and T2 glottic carcinoma is controversial. The purpose of this study was to assess the prognostic value of margin status in terms of local control. METHODS: Records of 266 patients treated from 1990 to 2013 were evaluated. Patients with previous cordectomy or without preoperative CT scan were excluded from the study. RESULTS: A total 110 patients (85 T1a, 8 T1b, and 17 T2) were enrolled. A local recurrence was observed in 23 patients. Five-year disease free survival was significantly impaired in patients with positive margins (p = .009) and in patients with deep involvement of the vocal muscle (p = .004). CONCLUSION: The present study shows that invaded margin is a factor of poor local control even though laser vaporization was systematically applied after resection. In case of deep vocal fold involvement, TLM should be extended beyond the vocal muscle to improve local control. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1804-1809, 2016. PMID- 27248846 TI - From the Editor-in-Chief's Desk. PMID- 27248847 TI - Conventional methanotrophs are responsible for atmospheric methane oxidation in paddy soils. AB - Soils serve as the biological sink of the potent greenhouse gas methane with exceptionally low concentrations of ~1.84 p.p.m.v. in the atmosphere. The as-yet uncultivated methane-consuming bacteria have long been proposed to be responsible for this 'high-affinity' methane oxidation (HAMO). Here we show an emerging HAMO activity arising from conventional methanotrophs in paddy soil. HAMO activity was quickly induced during the low-affinity oxidation of high-concentration methane. Activity was lost gradually over 2 weeks, but could be repeatedly regained by flush-feeding the soil with elevated methane. The induction of HAMO activity occurred only after the rapid growth of methanotrophic populations, and a metatranscriptome-wide association study suggests that the concurrent high- and low-affinity methane oxidation was catalysed by known methanotrophs rather than by the proposed novel atmospheric methane oxidizers. These results provide evidence of atmospheric methane uptake in periodically drained ecosystems that are typically considered to be a source of atmospheric methane. PMID- 27248848 TI - Effect of continuous ultrasonic irrigation on postoperative pain in mandibular molars with nonvital pulps: a randomized clinical trial. AB - AIM: To evaluate via a randomized clinical trial the effect of continuous ultrasonic irrigation (CUI) on postoperative pain in mandibular molars with nonvital pulps. METHODOLOGY: Seventy mandibular molars with nonvital pulps and apical periodontitis were treated endodontically using two different irrigation techniques. The patients were randomly allocated to one of two groups, CUI (n = 35) and syringe irrigation (SI) (n = 35). The CUI group received irrigant activation using a Proultra Piezoflow ultrasonic needle as the final irrigation protocol, whilst in the SI group, the final irrigation was performed using 27 gauge needle. All the patients were prescribed ibuprofen 400 mg to be taken every 8 h, if required. Postoperative pain using a visual analog scale and analgesic intake were recorded everyday for 7 days. Data were analysed using chi-Square, Mann-Whitney and multiple linear regression tests. RESULTS: Mean postoperative pain was lower in the CUI as compared to SI group, but the difference was significant on the first day only (P = 0.032). The overall 24-h pain prevalence was 41.4%. CUI had a lower incidence of pain (31.4%) as compared to the SI group (51.4%), but the difference was not significant (P > 0.05). No significant difference was observed in analgesic consumption between the groups (P > 0.05). Regression analysis revealed a significant association of mean postoperative pain at 24 h with the irrigant protocol (P = 0.017) and preoperative pain (P = 0.000). CONCLUSION: A significant difference was observed between CUI and syringe irrigation on the first postoperative day following chemo-mechanical preparation. However, the benefit observed was not clinically relevant. PMID- 27248849 TI - Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT. AB - Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation. PMID- 27248850 TI - Estrogen-Based Therapies and Depression in Women Who Naturally Enter Menopause Before Population Average. PMID- 27248852 TI - Left Displacement of the Abomasum in 4 Beef Calves. AB - BACKGROUND: Little is known about the occurrence rate, underlying etiology or treatment of left displacement of the abomasum in beef calves. OBJECTIVE: Describe the clinical presentation, diagnosis and treatment of left displacement of the abomasum in 4 beef calves. ANIMALS: Four client-owned beef breed calves with left displaced abomasum (LDA). METHODS: Retrospective case series. Hospital medical records were reviewed to identify all beef breed cattle under the age of 6 months diagnosed with LDA. RESULTS: Four beef calves were treated for left displacement of the abomasum. All four had a history of decreased appetite and left-sided abdominal distention. Two had recently been treated for necrotic laryngitis and one was being treated for clostridial abomasitis. Ultrasonography confirmed the abomasum to be displaced between the rumen and the left body wall in all calves. The calves were initially treated by rolling to correct the abomasal displacement. The abomasum redisplaced in 3 of 4 calves within 1 hour to 6 days; 1 calf developed a mesenteric volvulus. A right paramedian abomasopexy was performed in all cases. Three of 4 calves grew well and remained in the herd 6-18 months later; 1 calf was euthanized because of complications associated with necrotic laryngitis. CONCLUSIONS AND CLINICAL IMPORTANCE: Left displacement of the abomasum should be considered as a differential diagnosis for beef calves with abdominal distention. Concurrent necrotic laryngitis can increase the risk of abomasal displacement in beef calves. Treatment should include surgical correction as rolling is not curative and might be associated with mesenteric volvulus. PMID- 27248851 TI - Worldwide Phylogenetic Distributions and Population Dynamics of the Genus Histoplasma. AB - BACKGROUND: Histoplasma capsulatum comprises a worldwide complex of saprobiotic fungi mainly found in nitrogen/phosphate (often bird guano) enriched soils. The microconidia of Histoplasma species may be inhaled by mammalian hosts, and is followed by a rapid conversion to yeast that can persist in host tissues causing histoplasmosis, a deep pulmonary/systemic mycosis. Histoplasma capsulatum sensu lato is a complex of at least eight clades geographically distributed as follows: Australia, Netherlands, Eurasia, North American classes 1 and 2 (NAm 1 and NAm 2), Latin American groups A and B (LAm A and LAm B) and Africa. With the exception of the Eurasian cluster, those clades are considered phylogenetic species. METHODOLOGY/PRINCIPAL FINDINGS: Increased Histoplasma sampling (n = 234) resulted in the revision of the phylogenetic distribution and population structure using 1,563 aligned nucleotides from four protein-coding regions. The LAm B clade appears to be divided into at least two highly supported clades, which are geographically restricted to either Colombia/Argentina or Brazil respectively. Moreover, a complex population genetic structure was identified within LAm A clade supporting multiple monophylogenetic species, which could be driven by rapid host or environmental adaptation (~0.5 MYA). We found two divergent clades, which include Latin American isolates (newly named as LAm A1 and LAm A2), harboring a cryptic cluster in association with bats. CONCLUSIONS/SIGNIFICANCE: At least six new phylogenetic species are proposed in the Histoplasma species complex supported by different phylogenetic and population genetics methods, comprising LAm A1, LAm A2, LAm B1, LAm B2, RJ and BAC-1 phylogenetic species. The genetic isolation of Histoplasma could be a result of differential dispersion potential of naturally infected bats and other mammals. In addition, the present study guides isolate selection for future population genomics and genome wide association studies in this important pathogen complex. PMID- 27248853 TI - Risk of Neurological Insult in Competitive Deep Breath-Hold Diving. AB - CONTEXT: It has been widely believed that tissue nitrogen uptake from the lungs during breath-hold diving would be insufficient to cause decompression stress in humans. With competitive free diving, however, diving depths have been ever increasing over the past decades. METHODS: A case is presented of a competitive free-diving athlete who suffered stroke-like symptoms after surfacing from his last dive of a series of 3 deep breath-hold dives. A literature and Web search was performed to screen for similar cases of subjects with serious neurological symptoms after deep breath-hold dives. CASE DETAILS: A previously healthy 31-y old athlete experienced right-sided motor weakness and difficulty speaking immediately after surfacing from a breathhold dive to a depth of 100 m. He had performed 2 preceding breath-hold dives to that depth with surface intervals of only 15 min. The presentation of symptoms and neuroimaging findings supported a clinical diagnosis of stroke. Three more cases of neurological insults were retrieved by literature and Web search; in all cases the athletes presented with stroke-like symptoms after single breath-hold dives of depths exceeding 100 m. Two of these cases only had a short delay to recompression treatment and completely recovered from the insult. CONCLUSIONS: This report highlights the possibility of neurological insult, eg, stroke, due to cerebral arterial gas embolism as a consequence of decompression stress after deep breath-hold dives. Thus, stroke as a clinical presentation of cerebral arterial gas embolism should be considered another risk of extreme breath-hold diving. PMID- 27248854 TI - Indicators of HIV-risk resilience among men who have sex with men: a content analysis of online profiles. AB - Background: HIV-risk resilience, or positive adaptation in the face of risk, is increasingly being recognised as an important characteristic among men who have sex with men (MSM). However, resilience in the context of online partner seeking remains underexplored among MSM. Methods: Using content analysis methodology, this study operationalised indicators of HIV-risk resilience in the profiles of 933 MSM using a sexual networking website. HIV-risk resilience included endorsing foreplay only (non-penetrative sex) or a versatile sexual position; being "out" (e.g. disclosed sexual orientation), having a profile photo, seeking friendship, seeking a relationship, serosorting, not endorsing alcohol or drug use, safer sexual adventurism (e.g. role playing, bondage), and safer sex. Results: The majority of men were between 18 and 35 years old (76.0%) and 73.3% were racial/ethnic minorities. The mean number of resilience components endorsed was 5.2 (s.d. = 1.5; range 0-9). Nearly half (48.0%) reported being "out" and 68.7% had a profile photo. The majority of men were seeking relationships (66.5%) and/or friendships (69.7%), were sexually versatile (53.3%), and preferred safer sex only (76.3%). The majority did not endorse drug use (82.0%) and 25.4% did not endorse alcohol use. Nearly one-quarter (21.4%) endorsed sexual adventurism and 2.5% were serosorting by partner's HIV negative status. Conclusion: HIV-risk resilience may be common among MSM using sexual networking websites and may manifest in safer sex intentions. Rather than exclusively focusing on sexual risk reduction, health promotion efforts targeting MSM online should acknowledge, measure, and leverage existent HIV-risk resilience strategies in this group. PMID- 27248855 TI - Laparoscopic peritoneal lavage for perforated diverticulitis: are we any further forward? PMID- 27248856 TI - Pseudo 1-D Micro/Nanofluidic Device for Exact Electrokinetic Responses. AB - Conventionally, a 1-D micro/nanofluidic device, whose nanochannel bridged two microchannels, was widely chosen in the fundamental electrokinetic studies; however, the configuration had intrinsic limitations of the time-consuming and labor intensive tasks of filling and flushing the microchannel due to the high fluidic resistance of the nanochannel bridge. In this work, a pseudo 1-D micro/nanofluidic device incorporating air valves at each microchannel was proposed for mitigating these limitations. High Laplace pressure formed at liquid/air interface inside the microchannels played as a virtual valve only when the electrokinetic operations were conducted. The identical electrokinetic behaviors of the propagation of ion concentration polarization layer and current voltage responses were obtained in comparison with the conventional 1-D micro/nanofluidic device by both experiments and numerical simulations. Therefore, the suggested pseudo 1-D micro/nanofluidic device owned not only experimental conveniences but also exact electrokinetic responses. PMID- 27248857 TI - Monitoring conformational heterogeneity of the lid of DnaK substrate-binding domain during its chaperone cycle. AB - DnaK or Hsp70 of Escherichia coli is a master regulator of the bacterial proteostasis network. Allosteric communication between the two functional domains of DnaK, the N-terminal nucleotide-binding domain (NBD) and the C-terminal substrate- or peptide-binding domain (SBD) regulate its activity. X-ray crystallography and NMR studies have provided snapshots of distinct conformations of Hsp70 proteins in various physiological states; however, the conformational heterogeneity and dynamics of allostery-driven Hsp70 activity remains underexplored. In this work, we employed single-molecule Forster resonance energy transfer (sm-FRET) measurements to capture distinct intradomain conformational states of a region within the DnaK-SBD known as the lid. Our data conclusively demonstrate prominent conformational heterogeneity of the DnaK lid in ADP-bound states; in contrast, the ATP-bound open conformations are homogeneous. Interestingly, a nonhydrolysable ATP analogue, AMP-PNP, imparts heterogeneity to the lid conformations mimicking the ADP-bound state. The cochaperone DnaJ confers ADP-like heterogeneous lid conformations to DnaK, although the presence of the cochaperone accelerates the substrate-binding rate by a hitherto unknown mechanism. Irrespective of the presence of DnaJ, binding of a peptide substrate to the DnaK-SBD leads to prominent lid closure. Lid closure is only partial upon binding to molten globule-like authentic cellular substrates, probably to accommodate non-native substrate proteins of varied structures. PMID- 27248858 TI - Excess free histone H3 localizes to centrosomes for proteasome-mediated degradation during mitosis in metazoans. AB - The cell tightly controls histone protein levels in order to achieve proper packaging of the genome into chromatin, while avoiding the deleterious consequences of excess free histones. Our accompanying study has shown that a histone modification that loosens the intrinsic structure of the nucleosome, phosphorylation of histone H3 on threonine 118 (H3 T118ph), exists on centromeres and chromosome arms during mitosis. Here, we show that H3 T118ph localizes to centrosomes in humans, flies, and worms during all stages of mitosis. H3 abundance at the centrosome increased upon proteasome inhibition, suggesting that excess free histone H3 localizes to centrosomes for degradation during mitosis. In agreement, we find ubiquitinated H3 specifically during mitosis and within purified centrosomes. These results suggest that targeting of histone H3 to the centrosome for proteasome-mediated degradation is a novel pathway for controlling histone supply, specifically during mitosis. PMID- 27248859 TI - Cost-effectiveness of screening for DPYD polymorphisms to prevent neutropenia in cancer patients treated with fluoropyrimidines. AB - AIM: To compare the cost of screening for three mutations in the dihydropyrimidine dehydrogenase gene and the costs of treating severe fluoropyrimidine-induced neutropenia. MATERIALS & METHODS: The polymorphisms rs3918290 (DPYD*2A), rs67376798 (DPYD 2846A>T) and rs55886062 (1679T>G, DPYD*13) were genotyped using real-time PCR, TaqMan probes and a rapid cell lysis to provide PCR-ready DNA. RESULTS: We found that genotyping 1000 patients in our center cost ?6400 and that the mean cost of treating severe neutropenia was ?3044. Therefore, if severe fluoropyrimidine-induced neutropenia is reduced by genotyping the three DPYD variations in at least 2.21 cases per 1000 treated patients, then DPYD genotyping will prove cost effective. CONCLUSION: We demonstrated that real-time DPYD genotyping using TaqMan probes is cost effective in all fluoropyrimidine-based treatments. PMID- 27248860 TI - Electronic and Molecular Structure of the Transient Radical Photocatalyst Mn(CO)5 and Its Parent Compound Mn2(CO)10. AB - We present a time-resolved X-ray spectroscopic study of the structural and electronic rearrangements of the photocatalyst Mn2(CO)10 upon photocleavage of the metal-metal bond. Our study of the manganese K-edge fine structure reveals details of both the molecular structure and valence charge distribution of the photodissociated radical product. Transient X-ray absorption spectra of the formation of the Mn(CO)5 radical demonstrate surprisingly small structural modifications between the parent molecule and the resulting two identical manganese monomers. Small modifications of the local valence charge distribution are decisive for the catalytic activity of the radical product. The spectral changes reflect altered hybridization of metal-3d, metal-4p, and ligand-2p orbitals, particularly loss of interligand interaction, accompanied by the necessary spin transition due to radical formation. The spectral changes in the manganese pre- and main-edge region are well-reproduced by time-dependent density functional theory and ab initio multiple scattering calculations. PMID- 27248861 TI - Electrochemical pore filling strategy for controlled growth of magnetic and metallic nanowire arrays with large area uniformity. AB - While a variety of template-based strategies have been developed in the fabrication of nanowires (NWs), a uniform pore filling across the template still poses a major challenge. Here, we present a large area controlled pore filling strategy in the reproducible fabrication of various magnetic and metallic NW arrays, embedded inside anodic aluminum oxide templates. Using a diffusive pulsed electrodeposition (DPED) technique, this versatile strategy relies on the optimized filling of branched nanopores at the bottom of templates with Cu. Serving the Cu filled nanopores as appropriate nucleation sites, the DPED is followed by a uniform and homogeneous deposition of magnetic (Ni and Fe) and metallic (Cu and Zn) NWs at a current density of 50 mA cm-2 for an optimal thickness of alumina barrier layer (~18 nm). Our strategy provides large area uniformity (exceeding 400 MUm2) in the fabrication of 16 MUm long free-standing NW arrays. Using hysteresis loop measurements and scanning electron microscopy images, the electrodeposition efficiency (EE) and pore filling percentage (F p) are evaluated, leading to maximum EE and F p values of 91% and 95% for Ni and Zn, respectively. Moreover, the resulting NW arrays are found to be highly crystalline. Accordingly, the DPED technique is capable of cheaply and efficiently controlling NW growth over a large area, providing a tool for various nanoscale applications including biomedical devices, electronics, photonics, magnetic storage medium and nanomagnet computing. PMID- 27248862 TI - How do Dutch GPs address work-related problems? A focus group study. AB - BACKGROUND: In the Netherlands, there is a lack of knowledge about general practitioners' (GPs) perception of their role regarding patients' occupation and work related problems (WRP). As work and health are closely related, and patients expect help from their GPs in this area, a better understanding is needed of GPs' motivation to address WRP. OBJECTIVES: To explore GPs' opinions on their role in the area of work and health. METHODS: This is a qualitative study using three focus groups with Dutch GPs from the catchment area of a hospital in the Southeast of the Netherlands. The group was heterogeneous in characteristics such as sex, age, and practice setting. Three focus groups were convened with 18 GPs. The moderator used an interview guide. Two researchers analysed verbatim transcripts using constant comparative analysis. RESULTS: We distinguished three items: (a) work context in a GP's integrated consultation style; (b) counselling about sick leave; (c) cooperation with occupational physicians (OPs). The participants are willing to address the topic and counsel about sick leave. They consider WRP in patients with medically unexplained symptoms (MUS) challenging. They tend to advise these patients to continue working as they think this will ultimately benefit them. CONCLUSION: The participating GPs seemed well aware of the relation between work and health but need more knowledge, communication skills and better cooperation with occupational physicians to manage work-related problems. [Box: see text]. PMID- 27248905 TI - Gentiopicroside and sweroside from Veratrilla baillonii Franch. induce phosphorylation of Akt and suppress Pck1 expression in hepatoma cells. AB - The use of phytochemicals and herbal medicines has accompanied human history. Advances in modern biomedical sciences have allowed us to investigate the functional mechanisms of herbal medicines and phytochemicals. Veratrilla baillonii Franch. has long been used as a medicinal herb in southwestern China. Here, we analyzed the effects of an ethanol extract from V. baillonii (VBFE) on the expression levels of the cytosolic form of the phosphoenolpyruvate carboxykinase gene (Pck1) mRNA and components of the insulin signalling cascade in HL1C hepatoma cells. Compared with the insulin control, VBFE treatment inhibited the expression of Pck1 mRNA in a dose-dependent manner. This was associated with the phosphorylation of Akt and Erk1/2 in a time-dependent manner. Further analysis of the purified components of VBFE indicated that gentiopicroside and sweroside from VBFE, alone and in combination, suppressed Pck1 expression and induced Akt and Erk1/2 phosphorylation. In conclusion, gentiopicroside and sweroside suppress Pck1 expression and induce phosphorylation of components in the insulin signalling cascade. This is the first study to demonstrate that gentiopicroside and sweroside show insulin-mimicking effects on the regulation of Pck1 expression. Further studies are warranted to explore the potential of gentiopicroside and sweroside in the control of blood glucose in animals. PMID- 27248906 TI - Deep Sequencing of Cell-Free Peripheral Blood DNA as a Reliable Method for Confirming the Diagnosis of Myelodysplastic Syndrome. AB - BACKGROUND: Demonstrating the presence of myelodysplastic syndrome (MDS)-specific molecular abnormalities can aid in diagnosis and patient management. We explored the potential of using peripheral blood (PB) cell-free DNA (cf-DNA) and next generation sequencing (NGS). MATERIALS AND METHODS: We performed NGS on a panel of 14 target genes using total nucleic acid extracted from the plasma of 16 patients, all of whom had confirmed diagnoses for early MDS with blasts <5%. PB cellular DNA from the same patients was sequenced using conventional Sanger sequencing and NGS. RESULTS: Deep sequencing of the cf-DNA identified one or more mutated gene(s), confirming the diagnosis of MDS in all cases. Five samples (31%) showed abnormalities in cf-DNA by NGS that were not detected by Sanger sequencing on cellular PB DNA. NGS of PB cell DNA showed the same findings as those of cf DNA in four of five patients, but failed to show a mutation in the RUNX1 gene that was detected in one patient's cf-DNA. Mutant allele frequency was significantly higher in cf-DNA compared with cellular DNA (p = 0.008). CONCLUSION: These data suggest that cf-DNA when analyzed using NGS is a reliable approach for detecting molecular abnormalities in MDS and should be used to determine if bone marrow aspiration and biopsy are necessary. PMID- 27248908 TI - TxCell. PMID- 27248907 TI - Cost-effectiveness of alternative colonoscopy surveillance strategies to mitigate metachronous colorectal cancer incidence. AB - BACKGROUND: The incidence of metachronous colorectal cancer (MCRC) among colorectal cancer (CRC) survivors varies significantly, and the optimal colonoscopy surveillance practice for mitigating MCRC incidence is unknown. METHODS: A cost-effectiveness analysis was used to compare the performances of the US Multi-Society Task Force guideline and all clinically reasonable colonoscopy surveillance strategies for 50- to 79-year-old posttreatment CRC patients with a computer simulation model. RESULTS: The US guideline [(1,3,5)] recommends the first colonoscopy 1 year after treatment, whereas the second and third colonoscopies are to be repeated at 3- and 5-year intervals. Some promising alternative cost-effective strategies were identified. In comparison with the US guideline, under various scenarios for a 20-year period, 1) reducing the surveillance interval of the guideline after the first colonoscopy by 1 year [(1,2,5)] would save up to 78 discounted life-years (LYs) and prevent 23 MCRCs per 1000 patients (incremental cost-effectiveness ratio [ICER] <= $23,270/LY), 2) reducing the intervals after the first and second negative colonoscopies by 1 year [(1,2,4)] would save/prevent up to 109 discounted LYs and 36 MCRCs (ICER <= $52,155/LY), and 3) reducing the surveillance intervals after the first and second negative colonoscopy by 1 and 2 years [(1,2,3)] would save/prevent up to 141 discounted LYs and 50 MCRCs (ICER <= $63,822/LY). These strategies would require up to 1100 additional colonoscopies per 1000 patients. Although the US guideline might not be cost-effective in comparison with a less intensive oncology guideline [(3,3,5); the ICER could be as high as $140,000/LY], the promising strategies would be cost-effective in comparison with such less intensive guidelines unless the cumulative MCRC incidence were very low. CONCLUSIONS: The US guideline might be improved by a slight increase in the surveillance intensity at the expense of moderately increased cost. More research is warranted to explore the benefits/harms of such practices. Cancer 2016;122:2560-70. (c) 2016 American Cancer Society. PMID- 27248966 TI - Complexation Behavior of the Tri-n-butyl Phosphate Ligand with Pu(IV) and Zr(IV): A Computational Study. AB - Tri-n-butyl phosphate (TBP), used as the extractant in nuclear fuel reprocessing, shows superior extraction abilities for Pu(IV) over a large number of fission products including Zr(IV). We have applied density functional theory (DFT) calculations to explain this selectivity by investigating differences in electronic structures of Pu(NO3)4.2TBP and Zr(NO3)4.2TBP complexes. On the basis of our quantum chemical calculations, we have established the lowest energy electronic states for both complexes; the quintet is the ground state for the former, whereas the latter exists in the singlet spin state. The calculated structural parameters for the optimized geometry of the plutonium complex are in agreement with the experimental results. Atoms in Molecules analysis revealed a considerable amount of ionic character to M-O{TBP} and M-O{NO3} bonds. Additionally, we have also investigated the extraction behavior of TBP for metal nitrates and have estimated the extraction energies to be -73.1 and -57.6 kcal/mol for Pu(IV) and Zr(IV), respectively. The large extraction energy of Pu(IV) system is in agreement with the observed selectivity in the extraction of Pu. PMID- 27248975 TI - Hepatic Angiomyolipoma Versus Hepatocellular Carcinoma in the Noncirrhotic Liver on Gadoxetic Acid-Enhanced MRI: A Diagnostic Challenge. AB - OBJECTIVE: The purpose of this study is to describe the imaging characteristics of hepatic angiomyolipoma (AML) on gadoxetic acid-enhanced MRI and to identify imaging features that are helpful for differentiating it from hepatocellular carcinoma (HCC) in a noncirrhotic liver. MATERIALS AND METHODS: We retrospectively identified 18 patients with pathologically proven hepatic AMLs who had undergone gadoxetic acid-enhanced MRI between 2008 and 2012. We randomly chose 36 patients with noncirrhotic liver who had a single HCC diagnosed radiologically during the same period. None of the HCCs was of the fibrolamellar variant. Two readers reviewed images in consensus to assess the lesion size, the presence of fat, signal intensity characteristics, enhancement profile, early draining veins, intratumoral vessels, and tumor capsules. The tumor-to-liver contrast ratios were measured. These features and the measurements were compared between the two groups. RESULTS: AMLs are more commonly found in women (83.3%), whereas HCCs are more common in men (75%) (p < 0.01). The size of AMLs (3.4 cm) and HCCs (4.3 cm) did not differ significantly. Intratumoral fat was identified in both AMLs (50.0%) and HCCs (30.6%). The dynamic enhancement profile (arterial hypervascularity and hypointensity during the delayed phase) was similar qualitatively and quantitatively except for the portal phase. AMLs and HCCs differed significantly with regard to isointensity on DWI (16.7% vs 0.0%; p = 0.03), washout in the portal phase (61.1% vs 88.9%; p = 0.03), early draining veins (27.8% vs 2.8%; p = 0.01), intratumoral vessels (55.6% vs 22.2%; p = 0.03), and presence of capsule (11.1% vs 50.0%; p = 0.01). CONCLUSION: On gadoxetic acid enhanced MRI of noncirrhotic liver, AML is often indistinguishable from HCC on the basis of the enhancement profiles. Female sex and some imaging features including DWI could facilitate the differentiation. PMID- 27248976 TI - An audit of the predictors of outcome in status epilepticus from a resource-poor country: a comparison with developed countries. AB - Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1+/-20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non-convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second-line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common. Treatment delay was frequent and adversely affected the outcome. PMID- 27248977 TI - Lower birth rate in patients with total hip replacement. AB - Background and purpose - There have been few studies on the effect of THR on pregnancy or delivery, and they have mainly been based on small and regional data. We evaluated the birth rate nationwide in patients of fertile age with THR. Patients and methods - This nationwide population-based cohort study was based on registry data on 5,863 Finnish THR patients who had undergone a THR between 1985 and 2006, and who were aged 15-45 years (females) or 15-50 years (males) at the time of THR. The matched reference cohort consisted of 17,575 sex- and age matched individuals (3 for each patient) who were alive and resident in Finland at the time of the patient's THR. Birth rate and Cox hazard ratios (HRs) with 95% CI for live births were calculated. Results - The birth rate after THR was approximately 20-60% lower in the male and female patient groups than in the reference individuals. The probability of having a live birth after THR was lower in female patients than in reference individuals, in all but the oldest age group (40-45 years). The same phenomenon was seen in male patients in all but the youngest age group (15-19 years). Adjustment for potential confounders increased the probability of THR patients having a live birth compared to reference individuals, but the birth rate was still clearly reduced (in men, adjusted HR =0.80, 95% CI: 0.69-0.92; in women, adjusted HR =0.56, 95% CI: 0.46-0.68). Interpretation - THR has a substantial effect on the birth rate of offspring, in both women and men. THR patients had a lower birth rate and probability of having a child after surgery, even after taking possible confounders into account. PMID- 27248978 TI - Prevention of Hospital-Acquired Infections. AB - BACKGROUND: Hospital-acquired infections (HAIs) are a persistent concern and include surgical site infections, intravascular line-associated infections, pneumonia, catheter-associated urinary tract infections, and C. difficile infection. METHOD: Review of the pertinent English-language literature. RESULTS: Hospital-acquired infections result in significant increases in morbidity, mortality rates, and cost and are a focus of efforts at reduction. CONCLUSION: I discuss efforts specific to each of the most common infections and a philosophical approach to prevention that strives to achieve zero potentially preventable hospital-acquired infections. PMID- 27248979 TI - Enhancement of Wound Healing by Non-Thermal N2/Ar Micro-Plasma Exposure in Mice with Fractional-CO2-Laser-Induced Wounds. AB - Micro-plasma is a possible alternative treatment for wound management. The effect of micro-plasma on wound healing depends on its composition and temperature. The authors previously developed a capillary-tube-based micro-plasma system that can generate micro-plasma with a high nitric oxide-containing species composition and mild working temperature. Here, the efficacy of micro-plasma treatment on wound healing in a laser-induced skin wound mouse model was investigated. A partial thickness wound was created in the back skin of each mouse and then treated with micro-plasma. Non-invasive methods, namely wound closure kinetics, optical coherence tomography (OCT), and laser Doppler scanning, were used to measure the healing efficiency in the wound area. Neo-tissue growth and the expressions of matrix metallopeptidase-3 (MMP-3) and laminin in the wound area were assessed using histological and immunohistochemistry (IHC) analysis. The results show that micro-plasma treatment promoted wound healing. Micro-plasma treatment significantly reduced the wound bed region. The OCT images and histological analysis indicates more pronounced tissue regrowth in the wound bed region after micro-plasma treatment. The laser Doppler images shows that micro-plasma treatment promoted blood flow in the wound bed region. The IHC results show that the level of laminin increased in the wound bed region after micro-plasma treatment, whereas the level of MMP-3 decreased. Based on these results, micro plasma has potential to be used to promote the healing of skin wounds clinically. PMID- 27248980 TI - Sustainable conversion of agriculture wastes into activated carbons: energy balance and arsenic removal from water. AB - The aims of this study are to investigate the production of activated carbons (AC) from Senegal agricultural wastes such as cashew shells, millet stalks and rice husks and to implement them in adsorption processes devoted to arsenic (V) removal. AC were produced by a direct physical activation with water steam without other chemicals. This production of AC has also led to co-products (gas and bio-oil) which have been characterized in terms of physical, chemical and thermodynamical properties for energy recovery. Considering the arsenic adsorption results and the energy balance for the three studied biomasses, the first results have shown that the millet stalks seem to be more interesting for arsenate removal from natural water and an energy recovery with a GEEelec of 18.9%. Cashew shells, which have shown the best energy recovery (34.3%), are not suitable for arsenate removal. This global approach is original and contributes to a recycling of biowastes with a joint recovery of energy and material. PMID- 27248981 TI - Outstanding Antibiofilm Features of Quanta-CuO Film on Glass Surface. AB - Intelligently designed surface nanoarchitecture provides defined control over the behavior of cells and biomolecules at the solid-liquid interface. In this study, CuO quantum dots (quanta-CuO; ~3-5 nm) were synthesized by a simple, low temperature solution process and further formulated as paint to construct quanta CuO thin film on glass. Surface morphological characterizations of the as-coated glass surface reveal a uniform film thickness (~120 +/- 10 nm) with homogeneous distribution of quanta-CuO. The antibiofilm assay showed a very high contact bacteria-killing capacity of as-coated quanta-CuO glass surfaces toward Staphylococcus aureus and Escherichia coli. This efficient antibacterial/antibiofilm activity was ascribed to the intracellular reactive oxygen species (ROS) generated by the quanta-CuO attached to the bacterial cells, which leads to an oxidative assault and finally results in bacterial cell death. Although there is a significant debate regarding the CuO nanostructure's antibacterial mode of action, we propose both contact killing and/or copper ion release killing mechanisms for the antibiofilm activity of quanta-CuO paint. Moreover, synergism of quanta-CuO with conventional antibiotics was also found to further enhance the antibacterial efficacy of commonly used antibiotics. Collectively, this state-of-the-art design of quanta-CuO coated glass can be envisioned as promising candidates for various biomedical and environmental device coatings. PMID- 27248982 TI - Robust and stretchable indium gallium zinc oxide-based electronic textiles formed by cilia-assisted transfer printing. AB - Electronic textile (e-textile) allows for high-end wearable electronic devices that provide easy access for carrying, handling and using. However, the related technology does not seem to be mature because the woven fabric hampers not only the device fabrication process directly on the complex surface but also the transfer printing of ultrathin planar electronic devices. Here we report an indirect method that enables conformal wrapping of surface with arbitrary yet complex shapes. Artificial cilia are introduced in the periphery of electronic devices as adhesive elements. The cilia also play an important role in confining a small amount of glue and damping mechanical stress to maintain robust electronic performance under mechanical deformation. The example of electronic applications depicts the feasibility of cilia for 'stick-&-play' systems, which provide electronic functions by transfer printing on unconventional complex surfaces. PMID- 27248983 TI - The putative oncogene CPI-17 is up-regulated in schwannoma. PMID- 27248984 TI - An Approach to Characterizing the Complicated Sequential Metabolism of Salidroside in Rats. AB - Metabolic study of bioactive compounds that undergo a dynamic and sequential process of metabolism is still a great challenge. Salidroside, one of the most active ingredients of Rhodiola crenulata, can be metabolized in different sites before being absorbed into the systemic blood stream. This study proposed an approach for describing the sequential biotransformation process of salidroside based on comparative analysis. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to determine the relative contribution of each site to the total metabolism of salidroside. The results showed that salidroside was stable in digestive juice, and it was metabolized primarily by the liver and the intestinal flora and to a lesser extent by the gut wall. The sequential metabolism method described in this study could be a general approach to characterizing the metabolic routes in the digestive system for natural products. PMID- 27248985 TI - Molecular Genetic Characterization of an Anthrabenzoxocinones Gene Cluster in Streptomyces Sp. FJS31-2 for the Biosynthesis of BE-24566B and Zunyimycin Ale. AB - Genome mining is an effective tool used to discover novel natural products from actinomycetes. Genome sequence analysis of Streptomyces sp. FJS31-2 revealed the presence of one putative type II polyketide gene cluster (ABX), which may correspond to type II polyketide products including BE-24566B and its chloro derivatives. The addition of natural humus acid successfully activated the biosynthsis of the abx gene cluster. BE-24566B and its chloro-derivatives, named zunyimycin A, were also detected. The targeted deletion of the polyketide skeleton synthesis genes such as abxp, abxk, and abxs was performed in the wild strain to identify the gene cluster for BE-24566B biosynthesis. PMID- 27248986 TI - Clematichinenoside (AR) Attenuates Hypoxia/Reoxygenation-Induced H9c2 Cardiomyocyte Apoptosis via a Mitochondria-Mediated Signaling Pathway. AB - Mitochondria-mediated cardiomyocyte apoptosis is involved in myocardial ischemia/reperfusion (MI/R) injury. Clematichinenoside (AR) is a triterpenoid saponin isolated from the roots of Clematis chinensis with antioxidant and anti inflammatory cardioprotection effects against MI/R injury, yet the anti-apoptotic effect and underlying mechanisms of AR in MI/R injury remain unclear. We hypothesize that AR may improve mitochondrial function to inhibit MI/R-induced cardiomyocyte apoptosis. In this study, we replicated an in vitro H9c2 cardiomyocyte MI/R model by hypoxia/reoxygenation (H/R) treatment. The viability of H9c2 cardiomyocytes was determined by MTT assay; apoptosis was evaluated by flow cytometry and TUNEL experiments; mitochondrial permeability transition pore (mPTP) opening was analyzed by a calcein-cobalt quenching method; and mitochondrial membrane potential (DeltaPsim) was detected by JC-1. Moreover, we used western blots to determine the mitochondrial cytochrome c translocation to cytosolic and the expression of caspase-3, Bcl-2, and Bax proteins. These results showed that the application of AR decreased the ratio of apoptosis and the extent of mPTP opening, but increased DeltaPsim. AR also inhibited H/R-induced release of mitochondrial cytochrome c and decreased the expression of the caspase-3, Bax proteins. Conversely, it remarkably increased the expression of Bcl-2 protein. Taken together, these results revealed that AR protects H9c2 cardiomyocytes against H/R-induced apoptosis through mitochondrial-mediated apoptotic signaling pathway. PMID- 27248987 TI - Antioxidative and Antidiabetic Effects of Natural Polyphenols and Isoflavones. AB - Many polyphenols that contain more than two phenolic hydroxyl groups are natural antioxidants and can provide health benefits to humans. These polyphenols include, for example, oleuropein, hydroxytyrosol, catechin, chlorogenic acids, hesperidin, nobiletin, and isoflavones. These have been studied widely because of their strong radical-scavenging and antioxidative effects. These effects may contribute to the prevention of diseases, such as diabetes. Insulin secretion, insulin resistance, and homeostasis are important factors in the onset of diabetes, a disease that is associated with dysfunction of pancreatic beta-cells. Oxidative stress is thought to contribute to this dysfunction and the effects of antioxidants on the pathogenesis of diabetes have, therefore, been investigated. Here, we summarize the antioxidative effects of polyphenols from the perspective of their radical-scavenging activities as well as their effects on signal transduction pathways. We also describe the preventative effects of polyphenols on diabetes by referring to recent studies including those reported by us. Appropriate analytical approaches for evaluating antioxidants in studies on the prevention of diabetes are comprehensively reviewed. PMID- 27248988 TI - Significant Improvement of Metabolic Characteristics and Bioactivities of Clopidogrel and Analogs by Selective Deuteration. AB - In the search for prodrug analogs of clopidogrel with improved metabolic characteristics and antiplatelet bioactivity, a group of clopidogrel and vicagrel analogs selectively deuterated at the benzylic methyl ester group were synthesized, characterized, and evaluated. The compounds included clopidogrel-d3 (8), 2-oxoclopidogrel-d3 (9), vicagrel-d3 (10a), and 12 vicagrel-d3 analogs (10b 10m) with different alkyl groups in the thiophene ester moiety. The D3C-O bond length in 10a was shown by X-ray single crystal diffraction to be shorter than the H3C-O bond length in clopidogrel, consistent with the slower rate of hydrolysis of 8 than of clopidogrel in rat whole blood in vitro. A study of the ability of the compounds to inhibit ADP-induced platelet aggregation in fresh rat whole blood collected 2 h after oral dosing of rats with the compounds (7.8 MUmol/kg) showed that deuteration increased the activity of clopidogrel and that increasing the size of the alkyl group in the thiophene ester moiety reduced activity. A preliminary pharmacokinetic study comparing 10a with vicagrel administered simultaneously as single oral doses (72 MUmol/kg of each drug) to male Wistar rats showed 10a generated more of its active metabolite than vicagrel. These results suggest that 10a is a potentially superior antiplatelet agent with improved metabolic characteristics and bioactivity, and less dose related toxicity. PMID- 27248989 TI - Purification, Characterization and Biological Activity of Polysaccharides from Dendrobium officinale. AB - Polysaccharide (DOPA) from the stem of D. officinale, as well as two fractions (DOPA-1 and DOPA-2) of it, were isolated and purified by DEAE cellulose-52 and Sephacryl S-300 chromatography, and their structural characteristics and bioactivities were investigated. The average molecular weights of DOPA-1 and DOPA 2 were 394 kDa and 362 kDa, respectively. They were mainly composed of d-mannose, d-glucose, and had a backbone consisting of 1,4-linked beta-d-Manp and 1,4-linked beta-d-Glcp with O-acetyl groups. Bioactivity studies indicated that both DOPA and its purified fractions (DOPA-1 and DOPA-2) could activate splenocytes and macrophages. The D. officinale polysaccharides had stimulatory effects on splenocytes, T-lymphocytes and B-lymphocytes, promoting the cell viability and NO production of RAW 264.7 macrophages. Furthermore, DOPA, DOPA-1 and DOPA-2 were found to protect RAW 264.7 macrophages against hydrogen peroxide (H2O2)-induced oxidative injury by promoting cell viability, suppressing apoptosis and ameliorating oxidative lesions. These results suggested that D. officinale polysaccharides possessed antioxidant activity and mild immunostimulatory activity. PMID- 27248990 TI - The Effect of New Thiophene-Derived Aminophosphonic Derivatives on Growth of Terrestrial Plants: A Seedling Emergence and Growth Test. AB - The aim of this work was to synthesize selected thiophene-derived aminophosphonic systems and evaluate the phytotoxicity of newly obtained products according to the OECD 208 Guideline. Seven new thiophene-derived N-substituted dimethyl aminomethylphosphonic acid esters 2a-h were synthesized by the addition of an appropriate phosphite to azomethine bond of starting Schiff bases 1a-h, and NMR spectroscopic properties of aminophosphonates were investigated. These eight compounds were analyzed in regard to their phytotoxicity towards two plants, radish (Raphanus sativus) and oat (Avena sativa). On the basis of the obtained results, it was found that tested aminophosphonates 2a-h showed an ecotoxicological impact against selected plants, albeit to various degrees. PMID- 27248991 TI - A Deoxyuridine-Based Far-Red Emitting Viscosity Sensor. AB - A novel deoxyuridine (dU) benzothiazolium (BZ) derivative, referred to as dU-BZ, is reported that was synthesized via Sonogashira coupling reaction methodology. The deoxyuridine building block was introduced to enhance hydrophilicity, while an alkynylated benzothiazolium dye was incorporated for long wavelength absorption to reduce potential phototoxicity that is characteristic of using UV light to excite common fluorphores, better discriminate from native autofluorescence, and potentially facilitate deep tissue imaging. An impressive 30-fold enhancement of fluorescence intensity of dU-BZ was achieved upon increasing viscosity. Fluorescence quantum yields in 99% glycerol/1% methanol (v/v) solution as a function of temperature (293-343 K), together with viscosity dependent fluorescence lifetimes and radiative and non-radiative rate constants in glycerol/methanol solutions (ranging from 4.8 to 950 cP) were determined. Both fluorescence quantum yields and lifetimes increased with increased viscosity, consistent with results predicted by theory. This suggests that the newly designed compound, dU-BZ, is capable of functioning as a probe of local microviscosity, an aspect examined by in vitro bioimaging experiments. PMID- 27248992 TI - The Hedyotis diffusa Willd. (Rubiaceae): A Review on Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics. AB - Hedyotis diffusa Willd (H. diffusa) is a well-known Chinese medicine with a variety of activities, especially its anti-cancer effect in the clinic. Up to now, 171 compounds have been reported from H. diffusa, including 32 iridoids, 26 flavonoids, 24 anthraquinones, 26 phenolics and their derivatives, 50 volatile oils and 13 miscellaneous compounds. In vitro and in vivo studies show these phytochemicals and plant extracts to exhibit a range of pharmacological activities of anti-cancer, antioxidant, anti-inflammatory, anti-fibroblast, immunomodulatory and neuroprotective effects. Although a series of methods have been established for the quality control of H. diffusa, a feasible and reliable approach is still needed in consideration of its botanical origin, collecting time and bioactive effects. Meanwhile, more pharmacokinetics researches are needed to illustrate the characteristics of H. diffusa in vivo. The present review aims to provide up-to-date and comprehensive information on the phytochemistry, pharmacology, quality control and pharmacokinetic characteristics of H. diffusa for its clinical use and further development. PMID- 27248993 TI - Metabolic Profile Changes of CCl4-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule. AB - Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl4)-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl4 were inhibited after treatment of JGG, for 17 different metabolites related to CCl4. Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine. PMID- 27248994 TI - Trans-Fatty Acids Aggravate Obesity, Insulin Resistance and Hepatic Steatosis in C57BL/6 Mice, Possibly by Suppressing the IRS1 Dependent Pathway. AB - Trans-fatty acid consumption has been reported as a risk factor for metabolic disorders and targeted organ damages. Nonetheless, little is known about the roles and mechanisms of trans-fatty acids in obesity, insulin resistance (IR) and hepatic steatosis. Adult C57BL/6 male mice were fed with four different diets for 20 weeks: normal diet (ND), high fat diet (HFD), low trans-fatty acids diet (LTD) and high trans-fatty acid diet (HTD). The diet-induced metabolic disorders were assessed by evaluating body weight, glucose tolerance test, hepatic steatosis and plasma lipid profiles post 20-week diet. Histological (H&E, Oil-Red-O) staining and western blot analysis were employed to assess liver steatosis and potential signaling pathways. After 20-weeks of diet, the body weights of the four groups were 29.61 +/- 1.89 g (ND), 39.04 +/- 4.27 g (HFD), 34.09 +/- 2.62 g (LTD) and 43.78 +/- 4.27 g (HTD) (p < 0.05), respectively. HFD intake significantly impaired glucose tolerance, which was impaired further in the mice consuming the HTD diet. The effect was further exacerbated by HTD diet. Moreover, the HTD group exhibited significantly more severe liver steatosis compared with HFD group possibly through regulating adipose triglyceride lipase. The group consuming the HTD also exhibited significantly reduced levels of IRS1, phosphor-PKC and phosphor-AKT. These results support our hypothesis that consumption of a diet high in trans-fatty acids induces higher rates of obesity, IR and hepatic steatosis in male C57BL/6 mice, possibly by suppressing the IRS1dependent pathway. PMID- 27248995 TI - Recent Advances in Developing Small Molecules Targeting Nucleic Acid. AB - Nucleic acids participate in a large number of biological processes. However, current approaches for small molecules targeting protein are incompatible with nucleic acids. On the other hand, the lack of crystallization of nucleic acid is the limiting factor for nucleic acid drug design. Because of the improvements in crystallization in recent years, a great many structures of nucleic acids have been reported, providing basic information for nucleic acid drug discovery. This review focuses on the discovery and development of small molecules targeting nucleic acids. PMID- 27248996 TI - Hereditary Predispositions to Myelodysplastic Syndrome. AB - Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SBS), hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA) and significantly increased risks for MDS and/or acute myeloid leukemia (AML) in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes. PMID- 27248997 TI - Follicle Loss and Apoptosis in Cyclophosphamide-Treated Mice: What's the Matter? AB - With increasing numbers of young female cancer survivors following chemotherapy, chemotherapy-induced fertility loss must be considered. Menstrual disorder and infertility are of particular concern in female cancer patients. We showed that treatment with the alkylating agent cyclophosphamide (CTX) could cause severe primordial follicle loss and growing follicle apoptosis, resulting in loss of ovarian reserve. SPF C57BL/6 female mice were treated with a single dose of 120 mg/kg of CTX or saline as a control, and both sides of ovaries were collected three or seven days after injection. Following CTX treatment, the ovaries were mostly composed of collapsed oocytes and presented marked cortical fibrosis and a reduced number of follicles, especially primordial follicles. The loss of primordial follicles was confirmed by primordial follicle counting, immunohistochemistry and Western blot detection of DDx4/MVH. Follicle apoptosis was tested by a TUNEL assay and the number of TUNEL-positive follicle cells increased, as expected, in CTX-treated mice. Furthermore, expression of APAF-1 and cleaved caspase-3 was also increased after CTX treatment. Analysis of the PI3K/Akt/mTOR signaling pathway showed that CTX increased phosphorylation of Akt, mTOR and downstream proteins without affecting total levels. These results demonstrated that the CTX treatment led to the hyperactivation of the PI3K/Akt/mTOR signaling pathway in ovaries which may be related to primordial follicle loss and growing follicle apoptosis. PMID- 27248998 TI - A Chloroplast-Localized Rubredoxin Family Protein Gene from Puccinellia tenuiflora (PutRUB) Increases NaCl and NaHCO3 Tolerance by Decreasing H2O2 Accumulation. AB - Rubredoxin is one of the simplest iron-sulfur (Fe-S) proteins. It is found primarily in strict anaerobic bacteria and acts as a mediator of electron transfer participation in different biochemical reactions. The PutRUB gene encoding a chloroplast-localized rubredoxin family protein was screened from a yeast full-length cDNA library of Puccinellia tenuiflora under NaCl and NaHCO3 stress. We found that PutRUB expression was induced by abiotic stresses such as NaCl, NaHCO3, CuCl2 and H2O2. These findings suggested that PutRUB might be involved in plant responses to adversity. In order to study the function of this gene, we analyzed the phenotypic and physiological characteristics of PutRUB transgenic plants treated with NaCl and NaHCO3. The results showed that PutRUB overexpression inhibited H2O2 accumulation, and enhanced transgenic plant adaptability to NaCl and NaHCO3 stresses. This indicated PutRUB might be involved in maintaining normal electron transfer to reduce reactive oxygen species (ROS) accumulation. PMID- 27248999 TI - Expression and Characterization of a Novel Glycerophosphodiester Phosphodiesterase from Pyrococcus furiosus DSM 3638 That Possesses Lysophospholipase D Activity. AB - Glycerophosphodiester phosphodiesterases (GDPD) are enzymes which degrade various glycerophosphodiesters to produce glycerol-3-phosphate and the corresponding alcohol moiety. Apart from this, a very interesting finding is that this enzyme could be used in the degradation of toxic organophosphorus esters, which has resulted in much attention on the biochemical and application research of GDPDs. In the present study, a novel GDPD from Pyrococcus furiosus DSM 3638 (pfGDPD) was successfully expressed in Escherichia coli and biochemically characterized. This enzyme hydrolyzed bis(p-nitrophenyl) phosphate, one substrate analogue of organophosphorus diester, with an optimal reaction temperature 55 degrees C and pH 8.5. The activity of pfGDPD was strongly dependent on existing of bivalent cations. It was strongly stimulated by Mn(2+) ions, next was Co(2+) and Ni(2+) ions. Further investigations were conducted on its substrate selectivity towards different phospholipids. The results indicated that except of glycerophosphorylcholine (GPC), this enzyme also possessed lysophospholipase D activity toward both sn1-lysophosphatidylcholine (1-LPC) and sn2 lysophosphatidylcholine (2-LPC). Higher activity was found for 1-LPC than 2-LPC; however, no hydrolytic activity was found for phosphatidylcholine (PC). Molecular docking based on the 3D-modeled structure of pfGDPD was conducted in order to provide a structural foundation for the substrate selectivity. PMID- 27249000 TI - Goldfish Leptin-AI and Leptin-AII: Function and Central Mechanism in Feeding Control. AB - In mammals, leptin is a peripheral satiety factor that inhibits feeding by regulating a variety of appetite-related hormones in the brain. However, most of the previous studies examining leptin in fish feeding were performed with mammalian leptins, which share very low sequence homologies with fish leptins. To elucidate the function and mechanism of endogenous fish leptins in feeding regulation, recombinant goldfish leptin-AI and leptin-AII were expressed in methylotrophic yeast and purified by immobilized metal ion affinity chromatography (IMAC). By intraperitoneal (IP) injection, both leptin-AI and leptin-AII were shown to inhibit the feeding behavior and to reduce the food consumption of goldfish in 2 h. In addition, co-treatment of leptin-AI or leptin AII could block the feeding behavior and reduce the food consumption induced by neuropeptide Y (NPY) injection. High levels of leptin receptor (lepR) mRNA were detected in the hypothalamus, telencephalon, optic tectum and cerebellum of the goldfish brain. The appetite inhibitory effects of leptins were mediated by downregulating the mRNA levels of orexigenic NPY, agouti-related peptide (AgRP) and orexin and upregulating the mRNA levels of anorexigenic cocaine-amphetamine regulated transcript (CART), cholecystokinin (CCK), melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC) in different areas of the goldfish brain. Our study, as a whole, provides new insights into the functions and mechanisms of leptins in appetite control in a fish model. PMID- 27249002 TI - Adaptive Particle Filter for Nonparametric Estimation with Measurement Uncertainty in Wireless Sensor Networks. AB - Particle filters (PFs) are widely used for nonlinear signal processing in wireless sensor networks (WSNs). However, the measurement uncertainty makes the WSN observations unreliable to the actual case and also degrades the estimation accuracy of the PFs. In addition to the algorithm design, few works focus on improving the likelihood calculation method, since it can be pre-assumed by a given distribution model. In this paper, we propose a novel PF method, which is based on a new likelihood fusion method for WSNs and can further improve the estimation performance. We firstly use a dynamic Gaussian model to describe the nonparametric features of the measurement uncertainty. Then, we propose a likelihood adaptation method that employs the prior information and a belief factor to reduce the measurement noise. The optimal belief factor is attained by deriving the minimum Kullback-Leibler divergence. The likelihood adaptation method can be integrated into any PFs, and we use our method to develop three versions of adaptive PFs for a target tracking system using wireless sensor network. The simulation and experimental results demonstrate that our likelihood adaptation method has greatly improved the estimation performance of PFs in a high noise environment. In addition, the adaptive PFs are highly adaptable to the environment without imposing computational complexity. PMID- 27249001 TI - Enzyme Biosensors for Biomedical Applications: Strategies for Safeguarding Analytical Performances in Biological Fluids. AB - Enzyme-based chemical biosensors are based on biological recognition. In order to operate, the enzymes must be available to catalyze a specific biochemical reaction and be stable under the normal operating conditions of the biosensor. Design of biosensors is based on knowledge about the target analyte, as well as the complexity of the matrix in which the analyte has to be quantified. This article reviews the problems resulting from the interaction of enzyme-based amperometric biosensors with complex biological matrices containing the target analyte(s). One of the most challenging disadvantages of amperometric enzyme based biosensor detection is signal reduction from fouling agents and interference from chemicals present in the sample matrix. This article, therefore, investigates the principles of functioning of enzymatic biosensors, their analytical performance over time and the strategies used to optimize their performance. Moreover, the composition of biological fluids as a function of their interaction with biosensing will be presented. PMID- 27249004 TI - Iron, Anemia, and Iron Deficiency Anemia among Young Children in the United States. AB - Iron deficiency and anemia are associated with impaired neurocognitive development and immune function in young children. Total body iron, calculated from serum ferritin and soluble transferrin receptor concentrations, and hemoglobin allow for monitoring of the iron and anemia status of children in the United States. The purpose of this analysis is to describe the prevalence of iron deficiency (ID), anemia, and iron deficiency anemia (IDA) among children 1-5 years using data from the 2007-2010 National Health and Nutrition Examination Survey (NHANES). Prevalence of ID, anemia, and IDA among children 1-5 years was 7.1% (5.5, 8.7), 3.9% (2.0, 4.3), and 1.1% (0.6, 1.7), respectively. The prevalence of both ID and anemia were higher among children 1-2 years (p < 0.05). In addition, 50% of anemic children 1-2 years were iron deficient. This analysis provides an update on the prevalence of ID, anemia, and IDA for a representative sample of US children. Our results suggest little change in these indicators over the past decade. Monitoring of ID and anemia is critical and prevention of ID in early childhood should remain a public health priority. PMID- 27249003 TI - Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity. AB - Long non-coding RNA (lncRNA) CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP) rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29-0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30-0.89, p = 0.02, respectively). It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05-2.39, p = 0.03). Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC) subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35-0.98, p = 0.04) and in additive model (adjusted OR = 0.62, 95%CI = 0.43-0.90, p = 0.01). Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36-45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07-3.53, p = 0.03, respectively). Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients. PMID- 27249005 TI - Clinical Efficacy and Changes of Urothelial Dysfunction after Repeated Detrusor Botulinum Toxin A Injections in Chronic Spinal Cord-Injured Bladder. AB - Chornic spinal cord injury (SCI) will induce bladder urothelium dysfunction. This study investigated the therapeutic effects on urothelial dysfunction after repeated detrusor injections of onabotulinumtoxinA (BoNT-A) in SCI patients with neurogenic detrusor overactivity (NDO). Twenty chronic suprasacral SCI patients with NDO were enrolled. The patients received 300 U BoNT-A injection into the detrusor every six months. The urothelium was assessed by cystoscopic biopsy at baseline and six months after each BoNT-A treatment. Immunofluorescence staining for urothelial dysfunction, including E-cadherin, zonula occludens-1 (ZO-1), tryptase for mast cell activity, and urothelial apoptosis were investigated. The outcome of urothelial dysfunction parameters after BoNT-A injection were compared between baseline and six months after each treatment. Repeated 300 U BoNT-A injections showed a sustained decrease of detrusor pressure compared with baseline. After three repeated BoNT-A detrusor injections, significantly greater distributions of E-cadherin (p = 0.042) and ZO-1 (p = 0.003) expressions, but no significant changes, of urothelial apoptosis and mast cell activation were found after repeated BoNT-A therapy. Urothelial dysfunction, such as adhesive and junction protein concentrations in SCI patients' bladders, recovered after three repeated cycles of BoNT-A treatment. The therapeutic effects sustained. However, urothelial inflammation and apoptosis after SCI were not significantly improved after three repeated BoNT-A injections. PMID- 27249007 TI - Transepithelial High-Intensity Cross-Linking for the Treatment of Progressive Keratoconus: 2-year Outcomes. AB - PURPOSE: To report 2-year outcomes of transepithelial high-intensity cross linking (CXL) procedure in the treatment of patients with progressive keratoconus. METHODS: Forty-eight eyes of 48 consecutive progressive keratoconus patients who underwent transepithelial accelerated CXL procedure were enrolled in the study. Each patient underwent pre- and postoperative comprehensive ophthalmologic examinations including determination of refractive error as spherical equivalent (SE) and corrected distant visual acuity (CDVA), slit lamp biomicroscopic examination, fundoscopy, and a detailed analysis on a Scheimplug+Placido device (Sirius, CSO, Florence, Italy). The riboflavin solution, which was composed of riboflavin 0.25% with hydroxypropyl methylcellulose (HPMC) and benzalkonium chloride (BAC) (ParaCel, Avedro), was used in the procedure. The cornea was exposed to ultraviolet A light (KXL System, Avedro Inc., Waltham, MS, USA) for 2 minutes and 40 seconds at an irradiance of 45 mW/cm2. RESULTS: The mean age of the patients was 25.9 +/- 4.0 (ranging from 18 to 33) years. No significant changes were observed in the mean CDVA, SE, and topographic indices at year 1 and year 2 visits compared to preoperative examination. The mean corneal thickness at the thinnest point was significantly higher at year 1 and year 2 visits than at preoperative examination (p1 = 0.014 and p2 = 0.017, respectively). No intra- or postoperative complications or adverse reactions were observed. CONCLUSIONS: Transepithelial high-intensity (irradiance of 45 mW/cm2 for 2 minutes and 40 seconds) CXL using 0.25% riboflavin solution was a safe and effective method to halt the progression of keratoconus for a 2-year follow-up period. PMID- 27249006 TI - Tethered and Polymer Supported Bilayer Lipid Membranes: Structure and Function. AB - Solid supported bilayer lipid membranes are model systems to mimic natural cell membranes in order to understand structural and functional properties of such systems. The use of a model system allows for the use of a wide variety of analytical tools including atomic force microscopy, impedance spectroscopy, neutron reflectometry, and surface plasmon resonance spectroscopy. Among the large number of different types of model membranes polymer-supported and tethered lipid bilayers have been shown to be versatile and useful systems. Both systems consist of a lipid bilayer, which is de-coupled from an underlying support by a spacer cushion. Both systems will be reviewed, with an emphasis on the effect that the spacer moiety has on the bilayer properties. PMID- 27249009 TI - Impeded Immunity? Reduced Tuberculosis Vaccine Response with Exposure to Environmental Chemicals. PMID- 27249008 TI - Use of single chain antibody derivatives for targeted drug delivery. AB - Single chain antibodies (scFvs), which contain only the variable domains of full length antibodies, are relatively small molecules that can be used for selective drug delivery. In this review, we display how scFv antibodies help improve the specificity and efficiency of drugs. Small interfering RNA (siRNA) delivery using scFv-drug fusion peptides, siRNA delivery using scFv-conjugated nanoparticles, targeted delivery using scFv-viral peptide- fusion proteins, use of scFv in fusion with cell penetrating peptides for effective targeted drug delivery, scFv mediated targeted delivery of inorganic nanoparticles, scFv-mediated increase of tumor killing activity of granulocytes, use of scFv for tumor imaging, site directed conjugation of scFv molecules to drug carrier systems, use of scFv to relieve pain, use of scFv for increasing drug loading efficiency are among the topics that are discussed here. PMID- 27249010 TI - Development of harmonised food and sample lists for total diet studies in five European countries. AB - A total diet study (TDS) is a public health tool for determination of population dietary exposure to chemicals across the entire diet. TDSs have been performed in several countries but the comparability of data produced is limited. Harmonisation of the TDS methodology is therefore desirable and the development of comparable TDS food lists is considered essential to achieve the consistency between countries. The aim of this study is to develop and test the feasibility of a method for establishing harmonised TDS food and sample lists in five European countries with different consumption patterns (Czech Republic, Finland, Germany, Iceland and Portugal). The food lists were intended to be applicable for exposure assessment of wide range of chemical substances in adults (18-64 years) and the elderly (65-74 years). Food consumption data from recent dietary surveys measured on individuals served as the basis for this work. Since the national data from these five countries were not comparable, all foods were linked to the EFSA FoodEx2 classification and description system. The selection of foods for TDS was based on the weight of food consumed and was carried out separately for each FoodEx2 level 1 food group. Individual food approach was respected as much as possible when the TDS samples were defined. TDS food lists developed with this approach represented 94.7-98.7% of the national total diet weights. The overall number of TDS samples varied from 128 in Finland to 246 in Germany. The suggested method was successfully implemented in all five countries. Mapping of data to the EFSA FoodEx2 coding system was recognised as a crucial step in harmonisation of the developed TDS food lists. PMID- 27249014 TI - Incorrect Author Name in the Byline. PMID- 27249011 TI - Redox-Divergent Hydrogen-Retentive or Hydrogen-Releasing Synthesis of 3,4 Dihydroisoquinolines or Isoquinolines. AB - A rare Ru-catalyzed highly selective synthesis of 3,4-dihydroisoquinolines or isoquinolines is accomplished via a redox-divergent hydrogen-retentive or hydrogen-releasing fashion. Notably, high cis-selectivity of 3,4 dihydroisoquinolines is achieved. Potential applications are shown by gram-scale reactions and very concise synthesis of N-containing polycyclic aromatic compounds. Primary mechanistic investigations indicate that the sequence of the major pathway involves Ru-catalyzed C-H activation, alkyne insertion, and subsequent 6pi-electrocyclization. PMID- 27249015 TI - Crystallization of Keggin Heteropolyanions via a Two-Step Process in Aqueous Solutions. AB - Although the analytical simplicity of the one-step classical theory of nucleation facilitates its use to understand crystallization processes, recent experiments and simulations have shown that many occur via multiple steps. According to the contemporary two-stage theory of nucleation, the onset of crystallization in a solution is preceded by large density fluctuations in the mother liquor that results in the formation of dense liquid-like correlated structures of the constituent solute particles. Here we report the observation of dense liquid-like correlated structures of heteropolyacid salts of alpha-Keggin anions (heteropolyanions) in aqueous solutions as volume is decreased long before the onset of crystallization by in situ time-dependent small-angle X-ray scattering measurements. Experiments were performed on drying drops of solutions of heteropolyacids to monitor their ordering before and during the onset of their crystallization. A continuous change in the density of the correlated structures is observed up to the onset of crystallization. Moreover, the correlated structures and the onset of crystallization are found to depend upon the charge of the heteropolyanions. The crystals formed within the drying drops of solutions during the crystallization process are found to be metastable polymorphic structures that are different from the stable crystal structures obtained after complete drying of the drops. Our results support a two-step process and Ostwald's rule of stages for the crystallization of heteropolyanions in their aqueous solutions upon evaporation. PMID- 27249016 TI - Analysis of Performance on Cognitive Test Measures Before, During, and After 6 Months of Hearing Aid Use: A Single-Subject Experimental Design. AB - PURPOSE: The present study examined the effect of hearing aid use on cognitive test performance using a single-subject treatment design. METHOD: Six participants 54 to 64 years old with sensorineural hearing loss were fitted with hearing aids. Participants used the hearing aids for approximately 8 hr each day for the duration of the study. A battery of cognitive tests was administered to participants during baseline (pre-hearing aid fitting), treatment (hearing aid use), and withdrawal (post-hearing aid use) study phases over a period of 6 months of hearing aid use. RESULTS: All participants showed significant improvements in performance on the cognitive test measures with hearing aid use. The most significant treatment effects were evidenced at 2 to 4 weeks of hearing aid use on the Listening Span Test and an auditory selective attention task. In many cases, cognitive performance scores returned to baseline levels after the participant stopped using the hearing aids. CONCLUSION: The findings from this study are consistent with the hypothesis that hearing aid use may improve cognitive performance by improving audibility and decreasing the cognitive load of the listening task. PMID- 27249018 TI - Organocatalytic silyl transfer from silylborane to nitroalkenes for the synthesis of beta-silyl nitroalkanes and beta-silyl amines. AB - The silylation of a wide array of nitroalkenes is achieved by organocatalysts in yields up to 93%. The reaction is carried out in a toluene/water biphasic solvent under operationally simple conditions. Reduction of the nitro group provides efficient access to functionalized beta-silyl amines. PMID- 27249017 TI - cSPider - Evaluation of a Free and Open-Source Automated Tool to Analyze Corticomotor Silent Period. AB - BACKGROUND: The corticomotor silent period (CSP), as assessed noninvasively by transcranial magnetic stimulation (TMS) in the primary motor cortex, has been found to reflect intracortical inhibitory mechanisms. Analysis of CSP is mostly conducted manually. However, this approach is time-consuming, and comparison of results from different laboratories may be compromised by inter-rater variability in analysis. No open source program for automated analysis is currently available. METHODS/RESULTS: Here, we describe cross-validation with the manual analysis of an in-house written automated tool to assess CSP (cSPider). Results from automated routine were compared with results of the manual evaluation. We found high inter-method reliability between automated and manual analysis (p<0.001), and significantly reduced time for CSP analysis (median = 10.3 sec for automated analysis of 10 CSPs vs. median = 270 sec for manual analysis of 10 CSPs). cSPider can be downloaded free of charge. CONCLUSION: cSPider allows automated analysis of CSP in a reliable and time-efficient manner. Use of this open-source tool may help to improve comparison of data from different laboratories. PMID- 27249019 TI - Study on the Ultrahigh Quantum Yield of Fluorescent P,O-g-C3 N4 Nanodots and its Application in Cell Imaging. AB - Graphitic carbon nitride nanodots (g-C3 N4 nanodots), as a new kind of heavy metal-free quantum dots, have attracted considerable attention because of their unique physical and chemical properties. Although various methods to obtain g-C3 N4 nanodots have been reported, it is still a challenge to synthesize g-C3 N4 nanodots with ultrahigh fluorescence quantum yield (QY). In this study, highly fluorescent phosphorus/oxygen-doped graphitic carbon nitride (P,O-g-C3 N4 ) nanodots were prepared by chemical oxidation and hydrothermal etching of bulk P-g C3 N4 derived from the pyrolysis of phytic acid and melamine. The as-prepared P,O g-C3 N4 nanodots showed strong blue fluorescence and a relatively high QY of up to 90.2 %, which can be ascribed to intrinsic phosphorus/oxygen-containing groups, and surface-oxidation-related fluorescence enhancement. In addition, the P,O-g-C3 N4 nanodots were explored for cell imaging with excellent stability and biocompatibility, which suggest that they have great potential in biological applications. PMID- 27249020 TI - Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non Diabetics: Results from the GLOBAL Fluid Cohort Study. AB - BACKGROUND AND OBJECTIVES: Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. METHODS AND MATERIALS: We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. RESULTS: The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (beta = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (beta = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (beta = -0.0002, 95%CI 0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6-10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34). CONCLUSIONS: In prevalent non-diabetic patients, random glucose levels at a diabetic level are under recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses. PMID- 27249021 TI - New Material of the Pterosaur Gladocephaloideus Lu et al., 2012 from the Early Cretaceous of Liaoning Province, China, with Comments on Its Systematic Position. AB - Although there are nine genera of ctenochasmatoids reported from the Jehol Biota, at present each is known from a specimen that has either a skull or a relatively complete postcranial skeleton. A nearly complete juvenile specimen of Gladocephaloideus from the Lower Cretaceous Jiufotang Formation of Sihedang, Lingyuan of Liaoning Province is the most complete ctenochasmatoid preserved to date with a skull and postcranial skeleton. Based on the holotype (IG-CAGS 08-07) and the nearly complete new specimen (JPM 2014-004), the diagnosis of Gladocephaloideus is amended: approximately 50 teeth in total with sharp tips; small nasoantorbital opening, occupying approximately 13% of total skull length; ratio of prenarial rostrum length to skull length approximately 0.63; deep groove along the mid-line of the mandibular symphysis; length to width ratio of the longest cervical vertebra = 4.1; ratio of femur length to tibia length = 0.61; tibia as long as the wing-phalange 1. Phylogenetic analysis recovers Gladocephaloideus within the clade Ctenochasmatidae. Gladocephaloideus has a closer relationship to the Chinese Pterofiltrus rather than to other ctenochasmatid pterosaurs. Microstructure of limb bones implies that JPM 2014-004 represents an early juvenile of Gladocephaloideus jingangshanensis, and that the type specimen is not a fully grown specimen either. We assume that the holotype may equate to the late juvenile or sub-adult developmental stage of Gladocephaloideus. PMID- 27249022 TI - Magnetic Particle / Magnetic Resonance Imaging: In-Vitro MPI-Guided Real Time Catheter Tracking and 4D Angioplasty Using a Road Map and Blood Pool Tracer Approach. AB - PURPOSE: In-vitro evaluation of the feasibility of 4D real time tracking of endovascular devices and stenosis treatment with a magnetic particle imaging (MPI) / magnetic resonance imaging (MRI) road map approach and an MPI-guided approach using a blood pool tracer. MATERIALS AND METHODS: A guide wire and angioplasty-catheter were labeled with a thin layer of magnetic lacquer. For real time MPI a custom made software framework was developed. A stenotic vessel phantom filled with saline or superparamagnetic iron oxide nanoparticles (MM4) was equipped with bimodal fiducial markers for co-registration in preclinical 7T MRI and MPI. In-vitro angioplasty was performed inflating the balloon with saline or MM4. MPI data were acquired using a field of view of 37.3*37.3*18.6 mm3 and a frame rate of 46 volumes/sec. Analysis of the magnetic lacquer-marks on the devices were performed with electron microscopy, atomic absorption spectrometry and micro-computed tomography. RESULTS: Magnetic marks allowed for MPI/MRI guidance of interventional devices. Bimodal fiducial markers enable MPI/MRI image fusion for MRI based roadmapping. MRI roadmapping and the blood pool tracer approach facilitate MPI real time monitoring of in-vitro angioplasty. Successful angioplasty was verified with MPI and MRI. Magnetic marks consist of micrometer sized ferromagnetic plates mainly composed of iron and iron oxide. CONCLUSIONS: 4D real time MP imaging, tracking and guiding of endovascular instruments and in vitro angioplasty is feasible. In addition to an approach that requires a blood pool tracer, MRI based roadmapping might emerge as a promising tool for radiation free 4D MPI-guided interventions. PMID- 27249023 TI - Calcyclin Binding Protein/Siah-1 Interacting Protein Is a Hsp90 Binding Chaperone. AB - The Hsp90 chaperone activity is tightly regulated by interaction with many co chaperones. Since CacyBP/SIP shares some sequence homology with a known Hsp90 co chaperone, Sgt1, in this work we performed a set of experiments in order to verify whether CacyBP/SIP can interact with Hsp90. By applying the immunoprecipitation assay we have found that CacyBP/SIP binds to Hsp90 and that the middle (M) domain of Hsp90 is responsible for this binding. Furthermore, the proximity ligation assay (PLA) performed on HEp-2 cells has shown that the CacyBP/SIP-Hsp90 complexes are mainly localized in the cytoplasm of these cells. Using purified proteins and applying an ELISA we have shown that Hsp90 interacts directly with CacyBP/SIP and that the latter protein does not compete with Sgt1 for the binding to Hsp90. Moreover, inhibitors of Hsp90 do not perturb CacyBP/SIP Hsp90 binding. Luciferase renaturation assay and citrate synthase aggregation assay with the use of recombinant proteins have revealed that CacyBP/SIP exhibits chaperone properties. Also, CacyBP/SIP-3xFLAG expression in HEp-2 cells results in the appearance of more basic Hsp90 forms in 2D electrophoresis, which may indicate that CacyBP/SIP dephosphorylates Hsp90. Altogether, the obtained results suggest that CacyBP/SIP is involved in regulation of the Hsp90 chaperone machinery. PMID- 27249024 TI - Association of Metabolites with Obesity and Type 2 Diabetes Based on FTO Genotype. AB - The single nucleotide polymorphism rs9939609 of the gene FTO, which encodes fat mass and obesity-associated protein, is strongly associated with obesity and type 2 diabetes (T2D) in multiple populations; however, the underlying mechanism of this association is unclear. The present study aimed to investigate FTO genotype dependent metabolic changes in obesity and T2D. To elucidate metabolic dysregulation associated with disease risk genotype, genomic and metabolomic datasets were recruited from 2,577 participants of the Korean Association REsource (KARE) cohort, including 40 homozygous carriers of the FTO risk allele (AA), 570 heterozygous carriers (AT), and 1,967 participants carrying no risk allele (TT). A total of 134 serum metabolites were quantified using a targeted metabolomics approach. Through comparison of various statistical methods, seven metabolites were identified that are significantly altered in obesity and T2D based on the FTO risk allele (adjusted p < 0.05). These identified metabolites are relevant to phosphatidylcholine metabolic pathway, and previously reported to be metabolic markers of obesity and T2D. In conclusion, using metabolomics with the information from genome-wide association studies revealed significantly altered metabolites depending on the FTO genotype in complex disorders. This study may contribute to a better understanding of the biological mechanisms linking obesity and T2D. PMID- 27249025 TI - Myricetin arrests human telomeric G-quadruplex structure: a new mechanistic approach as an anticancer agent. AB - The use of small molecules to arrest G-quadruplex structure has become a potential strategy for the development and design of a new class of anticancer therapeutics. We have studied the interaction of myricetin, a plant flavonoid and a putative anticancer agent, with human telomeric G-quadruplex TTAGGG(TTAGGG)3 DNA. Reverse transcription PCR data revealed significant repression in hTERT expression in MCF-7 breast cancer cells upon increasing the concentration of myricetin. Further, we conducted a telomeric repeat amplification protocol assay to confirm the inhibition of telomerase by myricetin. Optical spectroscopic techniques like circular dichroism, UV spectroscopy and fluorescence spectroscopy revealed the formation of a stable myricetin-G-quadruplex complex. The thermodynamic parameters of myricetin-G-quadruplex complex formation, presented through isothermal titration calorimetry studies, indicate the binding process to be thermodynamically favorable. In addition, high resolution NMR spectroscopy in conjunction with molecular dynamics simulation is employed to provide detailed mechanistic insights into the binding in the myricetin-G-quadruplex complex at the atomic level. Our results thus propose a new mode of action of myricetin as an anticancer agent via arresting telomeric G-quadruplex structure. PMID- 27249026 TI - Optimization of Operation Parameters for Helical Flow Cleanout with Supercritical CO2 in Horizontal Wells Using Back-Propagation Artificial Neural Network. AB - Sand production and blockage are common during the drilling and production of horizontal oil and gas wells as a result of formation breakdown. The use of high pressure rotating jets and annular helical flow is an effective way to enhance horizontal wellbore cleanout. In this paper, we propose the idea of using supercritical CO2 (SC-CO2) as washing fluid in water-sensitive formation. SC-CO2 is manifested to be effective in preventing formation damage and enhancing production rate as drilling fluid, which justifies tis potential in wellbore cleanout. In order to investigate the effectiveness of SC-CO2 helical flow cleanout, we perform the numerical study on the annular flow field, which significantly affects sand cleanout efficiency, of SC-CO2 jets in horizontal wellbore. Based on the field data, the geometry model and mathematical models were built. Then a numerical simulation of the annular helical flow field by SC CO2 jets was accomplished. The influences of several key parameters were investigated, and SC-CO2 jets were compared to conventional water jets. The results show that flow rate, ambient temperature, jet temperature, and nozzle assemblies play the most important roles on wellbore flow field. Once the difference between ambient temperatures and jet temperatures is kept constant, the wellbore velocity distributions will not change. With increasing lateral nozzle size or decreasing rear/forward nozzle size, suspending ability of SC-CO2 flow improves obviously. A back-propagation artificial neural network (BP-ANN) was successfully employed to match the operation parameters and SC-CO2 flow velocities. A comprehensive model was achieved to optimize the operation parameters according to two strategies: cost-saving strategy and local optimal strategy. This paper can help to understand the distinct characteristics of SC CO2 flow. And it is the first time that the BP-ANN is introduced to analyze the flow field during wellbore cleanout in horizontal wells. PMID- 27249027 TI - Increased Epithelial Expression of CTGF and S100A7 with Elevated Subepithelial Expression of IL-1beta in Trachomatous Trichiasis. AB - PURPOSE: To characterize the histological appearance and expression of pro inflammatory mediators, growth factors, matrix metalloproteinases and biomarkers of epithelial-mesenchymal transition (EMT) in healthy control and trachomatous trichiasis (TT) conjunctival tissue. METHODS: Conjunctival biopsies were taken from 20 individuals with TT and from 16 individuals with healthy conjunctiva, which served as controls. Study participants were of varying ethnicity and were living in a trachoma-endemic region of northern Tanzania. Formalin-fixed paraffin embedded tissue sections were stained using hematoxylin and eosin or by immunohistochemistry using antibodies against: IL-1beta, IL-6, IL-17A, IL-22, CXCL5, S100A7, cleaved caspase 1 (CC1), PDGF, CTGF, TGFbeta2, MMP7, MMP9, E cadherin, vimentin, and alphaSMA. RESULTS: Tissue from TT cases had a greater inflammatory cell infiltrate relative to controls and greater disruption of collagen structure. CTGF and S100A7 were more highly expressed in the epithelium and IL-1beta was more highly expressed in the substantia propria of TT cases relative to controls. Latent TGFbeta2 was slightly more abundant in the substantia propria of control tissue. No differences were detected between TT cases and controls in the degree of epithelial atrophy, the number of myofibroblasts or expression of EMT biomarkers. CONCLUSIONS: These data indicate that the innate immune system is active in the immunopathology of trachoma, even in the absence of clinical inflammation. CTGF might provide a direct link between inflammation and fibrosis and could be a suitable target for therapeutic treatment to halt the progression of trachomatous scarring. PMID- 27249028 TI - NFKB1 Promoter DNA from nt+402 to nt+99 Is Hypomethylated in Different Human Immune Cells. AB - Sepsis, with a persistently high 90-day mortality of about 46%, is the third most frequent cause of death in intensive care units worldwide. Further understanding of the inflammatory signaling pathways occurring in sepsis is important for new efficient treatment options. Key regulator of the inflammatory response is the transcription factor NFkappaB. As we have recently shown, the -94 Ins/Del NFKB1 promoter polymorphism influences sepsis mortality. However, a molecular explanation is still missing. Thus, promoter activity might be varying depending on the NFKB1 genotype, explaining the genotype dependent mortality from sepsis, and one likely mechanism is the degree of promoter methylation. Therefore, we tested the hypothesis that NFkappaB mRNA expression is regulated by promoter methylation in human cell lines and primary immune cell cultures. First, we examined the methylation of the NFKB1 promoter in U937, REH and HL-60 cells. In the promoter region of nt+99/+229 methylation in all analyzed cell lines was below 1%. Following incubation with bacterial cell wall components, no significant changes in the frequency of promoter methylation in U937 and REH cells were measured and the methylation frequency was under 1%. However, NFkappaB1 mRNA expression was two-fold increased in U937 cells after 24 h incubation with LPS. By contrast, demethylation by 5-Aza-2'-deoxycytidine incubation enhanced NFkappaB1 expression significantly. In addition, we analyzed NFKB1 promoter methylation in primary cells from healthy volunteers depending on the NFKB1-94 Ins/Del genotype. Methylation in the promoter region from nt+402 to nt+99 was below 1%. Genotype dependent differences occurred in neutrophil cells, where DD-genotype was significantly more methylated compared to II genotype at nt+284/+402. Besides in the promoter region from nt-227/-8 in ID-genotypes methylation of neutrophils was significantly decreased compared to lymphocytes and in II-genotypes methylation in neutrophils was significantly decreased compared to lymphocytes and monocytes. In addition, CHART-PCR showed that the hypomethylated promoter regions are highly accessible. Therefore we assume that the demethylated regions are very important for NFKB1 promoter activity. PMID- 27249029 TI - Molecular identification and morphological description of Micropogonias megalops, Cynoscion othonopterus, C. reticulatus and Menticirrhus nasus larvae, collected in the upper Gulf of California during Summer 2012. AB - Sciaenidae fish larvae were collected from the upper Gulf of California during September 2012 using a conical net (505 MUm) through surface tows. These were pre classified into four larval morphotypes, based on external characteristics (mainly meristic and pigmentation). Partial sequences of cytochrome c oxidase, subunit 1 and 16S rRNA (16S) genes of mitochondrial DNA, were used in molecular genetic identification from each larval morphotype. Genetic results indicated the identification of four larval morphotypes as Micropogonias megalops, Cynoscion othonopterus, C. reticulatus and Menticirrhus nasus. Pigmentation patterns of larvae described after molecular genetic identification made it possible to distinguish between M. megalops, M. nasus and C. othonopterus (postflexion). However, pigmentation was not reliable for differentiating between preflexion larvae of C. othonopterus and C. reticulatus. From these results, both morphological and genetic approaches were proposed as complementary tools in taxonomic studies of ichthyoplankton, particularly in early fish larvae identification of congeneric species with similar morphological characteristics. PMID- 27249031 TI - One step at a time: CYP2D6 guided tamoxifen treatment awaits convincing evidence of clinical validity. PMID- 27249030 TI - Imaging in acute stroke. AB - INTRODUCTION: Stroke is the third leading cause of death and disability in Canada. In the hyperacute stroke setting, the treating physician must make a time critical decision on the treatment of each patient. Recent advances in imaging help the treating physician identify the subgroup of patients eligible for acute treatment of ischaemic stroke. AREAS COVERED: In this review we will discuss Non Contrast Computed Tomography (NCCT), CT-Angiography (CTA), and CT-Perfusion (CTP) in assessment of patients with acute ischaemic stroke and intracerebral haemorrhage. Intravenous tPA was the only proven therapy for acute ischaemic stroke presenting within 4.5 hours, until the five recent trials proved the efficacy of EVT for acute ischaemic stroke with proximal arterial occlusion. Imaging played a major role in patient selection in all five trials. Expert commentary: The challenge of rapid clinical assessment, review of imaging and timely treatment will continue to be made easier as the development and understanding of imaging progresses. PMID- 27249041 TI - Evaluation of basilar artery atherosclerotic plaque distribution by 3D MR vessel wall imaging. AB - PURPOSE: Basilar artery (BA) atherosclerosis is an important cause of perforator stroke in the brainstem due to plaque involvement of the perforator ostia in BA dorsal or lateral walls. Therefore, to acquire information on plaque distribution is important to better understand and prevent the perforator stroke. This study aimed to comprehensively evaluate BA plaque distribution with 3D magnetic resonance imaging (MRI) vessel wall imaging. MATERIALS AND METHODS: Consecutive patients with cerebrovascular symptoms and stenosis or irregular luminal surface of BA were recruited and underwent BA 3D proton density-weighted volume isotropic turbo spin echo acquisition (VISTA) imaging at 3T. The cross-sectional and longitudinal distribution of BA plaque were analyzed with a custom-developed tool. RESULTS: In all, 85 BA plaques were detected in 61 recruited patients. For cross-sectional distribution, the prevalence of plaque involvement in the ventral, left, dorsal, and right quadrant of BA wall was 74.1%, 70.6%, 67.1%, and 62.4%, respectively. Of the 85 plaques, 17.7% involved one quadrant and 82.3% involved two or more quadrants. The most severe plaque region was more commonly situated at lateral walls (66.1%) as compared to ventral (23.2%, P < 0.001) and dorsal walls (10.6%, P < 0.001). Longitudinally, plaques were more frequently found to occur at BA segment distal than proximal to anterior inferior cerebellar artery (AICA) (63.5% vs. 36.5%). CONCLUSION: Taking advantage of 3D MR vessel wall imaging, BA plaques were found to more likely affect lateral walls and form in BA distal to AICA, where most perforators originate, suggesting that it might be useful to characterize BA plaque distribution before aggressive treatment for prevention of perforator stroke. J. Magn. Reson. Imaging 2016;44:1592-1599. PMID- 27249043 TI - The relationship between clinical characteristics, metacognitive appraisals, and cognitive insight in patients with obsessive-compulsive disorder. AB - BACKGROUND: Cognitive insight, a recently developed insight measure, refers to metacognitive processes of the re-evaluation and correction of distorted beliefs and misinterpretations. However, to the best of the authors' knowledge, no study has specifically examined cognitive insight, demographics, psychopathological variables, and distorted beliefs in OCD. AIM: The aim of this research was to examine links between cognitive insight and demographics, clinical factors, and distorted beliefs among patients with OCD. METHOD: Eighty-four consecutive outpatients with a diagnosis of OCD underwent a detailed clinical assessment for OCD, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Cognitive Insight Scale (BCIS), Thought-Action Fusion Scale (TAFS), White Bear Thought Suppression Inventory, Metacognition Questioniarre-30 (MCQ-30), and a sociodemographic questionnaire. In addition, 82 control subjects matched for age, education, and gender were tested. RESULTS: BCIS-self-certainty scores were all substantially higher in subjects with remitted and unremitted OCD than in healthy comparison subjects, while BCIS-composite scores were significantly lower in both patient groups than controls. Obsession and compulsion severity had significant effects on BCIS scores. In addition, it was found that the specific symptoms were linked to self-certainty scores. Self-reflectiveness and composite scores had positive correlations with the sub-scale scores of the MCQ-30, while the TAF morality score was positively correlated with self-certainty scores. CONCLUSION: The results demonstrated poor cognitive insight among remitted and unremitted OCD patients. In addition, the present study suggested significant associations between sociodemographic and clinical features and dysfunctional appraisals. Cognitive-behavioural techniques aimed at enhancing cognitive insight may be beneficial for patients with OCD, particularly patients who have prominent dysfunctional beliefs. PMID- 27249044 TI - [Important Aspects of Diagnosis and Minimally Invasive Treatment of Metastases in the Spine Through the Plasma Field Therapy (Cavity Coblation Method)]. AB - Background and objectives: Until recently, it was almost impossible to perform major surgery on metastases in the spine. This is especially the case for multiple spinal metastases and for older multi-morbid patients with higher OP risks. It is very important in such cases that the operation should be as minimally invasive as possible, and should aim to reduce pain, treat fractures and to improve the quality of life. The aim of this publication is to present and discuss the specific features of the methodology, problems, surgical techniques, as well as the effectiveness of the modernised cavity/coblation method and results of the treatment of 240 patients with spine metastases. Patients/Material and Method: Patients: Patients of every age with bone destruction were treated, with osteolysis and pathological fractures of vertebrae caused by metastases. The pre-operative diagnosis was evaluated by X-Ray, MRT, CT, whole-body F18-FDG-PET, whole-body bone scintigraphy, histology. Cavity/coblation method: Tumour resection was carried out by the plasma field (42 degrees C, cold energy) over the percutaneous trans-/extrapedicular access and was followed by balloon kyphoplasty. Tumour tissue was removed, deformation corrected and stability enhanced. The treatment clearly reduced the risks of recurrence, fracture and compression of the neural structures. Local radiotherapy and chemotherapy were performed post-operatively. Clinical and radiological follow-ups, included tumour staging, were performed regularly after the OP (after 2 and 14 days and 3, 6,12, 24, 36, 48 and 60 months), including data on pain and improvement in quality of life. Results: Within 6 years (03/08-04/14), we treated 240 patients with multiple spinal metastases (146 female, 94 male, age range 31-92 years, average age 65.5 years) or 784 vertebral bodies. 61 patients were also given dorsal percutaneous instrumentation and straightening. All patients experienced a significant reduction in pain, and improvements in satisfaction and quality of life. Treatment was combined with chemotherapy and local radiotherapy to reduce tumour cell growth or recurrence rate. Patients could be rapidly mobilised after surgery, blood loss was minimal, and the next oncology treatment could be initiated immediately. Discussion/Conclusions: Cavity/coblation is a safe and minimally invasive procedure, as confirmed by our own short- and long-term results, as well as by reports/publications of other workers. OP risks, blood loss, and surgical time are lower and shorter. This new method is very promising for the future. It is important that the indication is correct and the treatment strategy must be adapted individually. Prognosis must be assessed and the surgical technique must be precise. PMID- 27249045 TI - [The Summer School of the German Society for Orthopaedics and Traumatology - A Success Story]. AB - Background: It has been known for several years that orthopaedic and trauma clinics suffer from a shortage of young people, due to the substantial loss in attractiveness. The Youth Forum OU has been addressing this problem for many years, by initiating many projects such as the Summer School to counteract this trend. The purpose of this research is to evaluate the success of Summer Schools since 2009. Methods: The Youth Forum OU performed a survey in December 2014 to answer the research question on the basis of an internet-based poll of the student participants in all Summer Schools between 2009 and 2014. Following data cleansing, 121 students and former students were included in the survey. Results: Seventy-two completed questionnaires were collected and included in the evaluation. The survey included 40 % of Summer School participants, with a mean age of 27.3 years (SD +/- 2.95); 50 % were female. Participation in the Summer School helped 50 % of the respondents to decide to start advanced study in orthopaedics and/or traumatology (OU). One third of these Summer School participants had already finished a university degree; 100 % are now residents in orthopaedics and/or traumatology. Regardless of prior plans, 87.2 % of participants are now residents in OU. Thirty-three are still students: 78.8 % have already decided to work in OU. The survey also served to identify the factors positively and negatively associated with OU. Unfavourable factors included the reputation of OU, and the difficulty of reconciling family and work. Favourable factors included surgical work and personal experience during university studies. Discussion: The aim of this study was to evaluate whether the efforts of the Youth Forum OU, the German Society for Orthopaedics and Traumatology (DGOU) and the local hospitals lead to increased interest in OU. The answer to this question is positive. This is particularly true for those students who did not plan to become an orthopaedic or trauma surgeon before participating in a Summer School. In conclusion, the efforts to recruit residents for OU by using Summer Schools were successful. Moreover, this research offers approaches to counteract the loss of attractiveness of OU. PMID- 27249046 TI - [Influence of Peridural Infiltration Therapy on Postural Control in Chronic Pain of the Lower Lumbar Spine - A Prospective Clinical Study]. AB - Background: Postural control, balance stability, is reduced in patients with chronic low back pain, due to pain. Epidural injection therapy (EI) is an established treatment of low back pain. The objective of our study was to investigate whether EI-induced pain relief also leads to improvement in postural control, as detected by computerised dynamic posturography (CDP). Patients and Methods: In a prospective study, 32 patients underwent CDP during and after the EI series of three injections. The main objective was to measure changes in overall stability index (OSI) in a pre- and post-intervention comparison. Results: The pain, measured by the Visual Analog Scale (VAS), decreased by 62.8 %, from 4.3 +/- 2.5 points to 1.6 +/- 1.9 points (p < 0.001). Likewise, the OSI improved by 21.6 %, from 3.7 +/- 1.7 degrees to 2.9 +/- 1.4 degrees (day 5) (p = 0.019). Conclusion: Pain relief induced by EI results in improved postural control, which is of importance for supportive physiotherapy and rehabilitation. PMID- 27249047 TI - [Acetabular Osteolysis in Total Hip Replacement - When to Retain the Cup?]. AB - Periacetabular osteolysis is a frequent long-term complication of cementless total hip arthroplasty. The decision whether to retain or to revise a cup in the presence of osteolysis remains a challenge. The options are regular clinical and radiological check-ups, isolated liner exchange with and without bone grafting, and complete cup revision. Thorough preoperative diagnostics, including a medical history, examination and imaging, are mandatory for correct decision making. In most patients, computed tomography is useful to assess periacetabular osteolysis. If the cup is well-fixed and positioned in an asymptomatic patient without progressive osteolysis and no implant defect or higher grade polyethylene wear and no signs of infection, continuous clinical and radiological monitoring is preferred. If imaging reveals cup loosening, malposition, osteolysis localised in a weight-bearing area, imminent or present periprosthetic fractures, rapid progressive osteolysis, implant defects or massive inlay wear, surgical treatment may be preferred. Cup revision is usually performed in such patients. If the cup is well-positioned and well-fixed in the X-ray, the procedure has to be discussed with the patient individually. Apart from patient-specific risk factors, the risk of further progression has to be assessed. Isolated liner exchange can be performed if the patient is asymptomatic and the cup proves to be stable intraoperatively. It is still unclear whether filling osteolyses through screw holes or osseous windows is of long-term benefit. PMID- 27249048 TI - The EffectLiteR Approach for Analyzing Average and Conditional Effects. AB - We present a framework for estimating average and conditional effects of a discrete treatment variable on a continuous outcome variable, conditioning on categorical and continuous covariates. Using the new approach, termed the EffectLiteR approach, researchers can consider conditional treatment effects given values of all covariates in the analysis and various aggregates of these conditional treatment effects such as average effects, effects on the treated, or aggregated conditional effects given values of a subset of covariates. Building on structural equation modeling, key advantages of the new approach are (1) It allows for latent covariates and outcome variables; (2) it permits (higher order) interactions between the treatment variable and categorical and (latent) continuous covariates; and (3) covariates can be treated as stochastic or fixed. The approach is illustrated by an example, and open source software EffectLiteR is provided, which makes a detailed analysis of effects conveniently accessible for applied researchers. PMID- 27249049 TI - Topological protection of multiparticle dissipative transport. AB - Topological protection allows robust transport of localized phenomena such as quantum information, solitons and dislocations. The transport can be either dissipative or non-dissipative. Here, we experimentally demonstrate and theoretically explain the topologically protected dissipative motion of colloidal particles above a periodic hexagonal magnetic pattern. By driving the system with periodic modulation loops of an external and spatially homogeneous magnetic field, we achieve total control over the motion of diamagnetic and paramagnetic colloids. We can transport simultaneously and independently each type of colloid along any of the six crystallographic directions of the pattern via adiabatic or deterministic ratchet motion. Both types of motion are topologically protected. As an application, we implement an automatic topologically protected quality control of a chemical reaction between functionalized colloids. Our results are relevant to other systems with the same symmetry. PMID- 27249050 TI - Field Effect Modulation of Outer-Sphere Electrochemistry at Back-Gated, Ultrathin ZnO Electrodes. AB - Here we report field-effect modulation of solution electrochemistry at 5 nm thick ZnO working electrodes prepared on SiO2/degenerately doped Si gates. We find that ultrathin ZnO behaves like a 2D semiconductor, in which charge carriers electrostatically induced by the back gate lead to band edge shift at the front electrode/electrolyte interface. This, in turn, manipulates the charge transfer kinetics on the electrode at a given electrode potential. Experimental results and the proposed model indicate that band edge alignment can be effectively modulated by 0.1-0.4 eV depending on the density of states in the semiconductor and the capacitance of the gate/dielectric stack. PMID- 27249051 TI - Negative Suction Drain Through a Mini Periareolar Incision for the Treatment of Lactational Breast Abscess Shortens Hospital Stay and Increases Breastfeeding Rates. AB - BACKGROUND: Although breast abscess is a serious uncommon complication of mastitis with high morbidity rate, there is a lack of high-quality randomized trial to demonstrate the best treatments. We reported a novel way of applying negative suction drain through a mini periareolar incision. MATERIALS AND METHODS: We retrospectively analyzed and compared the clinical characteristics of 62 patients with lactational breast abscess in our department from August 2012 to April 2015. Thirty-two patients went through traditional incision and drainage (Group A) and 30 patients were placed on negative suction drain through mini periareolar incision (Group B). RESULTS: There is no significant difference between the two groups in terms of age, white blood cell (WBC) count, size of the abscess cavity, and positive rate of Staphylococcus aureus (SA) or methicillin resistant Staphylococcus aureus (MRSA). Patients in Group B had a shorter hospitalized stay (p = 0.003) and had a higher rate of continuation of breastfeeding (p < 0.005). CONCLUSION: Applying drain with negative suction pressure through a mini periareolar incision is an effective modality for treating lactational breast abscess and maintaining breastfeeding. PMID- 27249052 TI - Physical Cross-Linking Starch-Based Zwitterionic Hydrogel Exhibiting Excellent Biocompatibility, Protein Resistance, and Biodegradability. AB - In this work, a novel starch-based zwitterionic copolymer, starch-graft poly(sulfobetaine methacrylate) (ST-g-PSBMA), was synthesized via Atom Transfer Radical Polymerization. Starch, which formed the main chain, can be degraded completely in vivo, and the pendent segments of PSBMA endowed the copolymer with excellent protein resistance properties. This ST-g-PSBMA copolymer could self assemble into a physical hydrogel in normal saline, and studies of the formation mechanism indicated that the generation of the physical hydrogel was driven by electrostatic interactions between PSBMA segments. The obtained hydrogels were subjected to detailed analysis by scanning electron microscopy, swelling ratio, protein resistance, and rheology tests. Toxicity and hemolysis analysis demonstrated that the ST-g-PSBMA hydrogels possess excellent biocompatibility and hemocompatibility. Moreover, the cytokine secretion assays (IL-6, TNF-alpha, and NO) confirmed that ST-g-PSBMA hydrogels had low potential to trigger the activation of macrophages and were suitable for in vivo biomedical applications. On the basis of these in vitro results, the ST-g-PSBMA hydrogels were implanted in SD rats. The tissue responses to hydrogel implantation and the hydrogel degradation in vivo were determined by histological analysis (Hematoxylin and eosin, Van Gieson, and Masson's Trichrome stains). The results presented in this study demonstrate that the physical cross-linking, starch-based zwitterionic hydrogels possess excellent protein resistance, low macrophage-activation properties, and good biocompatibility, and they are a promising candidate for an in vivo biomedical application platform. PMID- 27249053 TI - Estrogen-Based Therapies and Depression in Women Who Naturally Enter Menopause Before Population Average-Reply. PMID- 27249054 TI - Potent Nematicidal Activity of Maleimide Derivatives on Meloidogyne incognita. AB - Different maleimide derivatives were synthesized and assayed for their in vitro activity on the soil inhabiting, plant-parasitic nematode Meloidogyne incognita, also known as root-knot nematode. The compounds maleimide, N-ethylmaleimide, N isopropylmaleimide, and N-isobutylmaleimide showed the strongest nematicidal activity on the second stage juveniles of the root-knot nematode with EC50/72h values of 2.6 +/- 1.3, 5.1 +/- 3.4, 16.2 +/- 5.4, and 19.0 +/- 9.0 mg/L, respectively. We also determined the nematicidal activity of copper sulfate, finding an EC50 value of 48.6 +/- 29.8 mg/L. When maleimide at 1 mg/L was tested in combination with copper sulfate at 50 mg/L, we observed 100% mortality of the nematodes. We performed a GC-MS metabolomics analysis after treating nematodes with maleimide at 8 mg/L for 24 h. This analysis revealed altered fatty acids and diglyceride metabolites such as oleic acid, palmitic acid, and 1-monopalmitin. Our results suggest that maleimide may be used as a new interesting building block for developing new nematicides in combination with copper salts. PMID- 27249055 TI - The role of Toll-like receptor 4 (TLR4) in cardiac ischaemic-reperfusion injury, cardioprotection and preconditioning. AB - Cardiac ischaemic-reperfusion injury (IRI) remains the primary cause of mortality throughout the developed world. Molecular mechanisms underlying IRI are complex and are often interlinked with each other driving a synergistic response. Toll like receptor 4 (TLR4), an immunosurveillance receptor, is known to enhance tissue injury during IRI by enhancing the inflammatory response. The release of endogenous components during IRI bind onto TLR4 leading to the activation of multiple signalling kinases. Once this event occurs these proteins are defined as danger associated molecular patterns molecules (DAMPs) or alarmins. Examples include heat shock proteins, high mobility group box one (HMGB1) and extracellular matrix proteins, all of which are involved in IRI. However, literature in the last two decades suggests that transient stimulation of TLR4 may suppress IRI and thus improve cardiac recovery. Furthermore, it remains to be seen what role TLR4 plays during ischaemic-preconditioning where acute bouts of ischaemia, preceding a harmful bout of ischaemic-reperfusion, is cardioprotective. The other question which also needs to be considered is that if transient TLR4 signalling drives a preconditioning response then what are the ligands which drive this? Hence the second part of this review explores the possible TLR4 ligands which may promote cardioprotection against IRI. PMID- 27249056 TI - How Accurate Are Home Blood Pressure Devices in Use? A Cross-Sectional Study. AB - BACKGROUND: Out of office blood pressure measurements, using either home monitors or 24 hour ambulatory monitoring, is widely recommended for management of hypertension. Though validation protocols, meant to be used by manufacturers, exist for blood pressure monitors, there is scant data in the literature about the accuracy of home blood pressure monitors in actual clinical practice. We performed a chart review in the blood pressure assessment clinic at a tertiary care centre. METHODS: We assessed the accuracy of home blood pressure monitors used by patients seen in the nephrology clinic in Ottawa between the years 2011 to 2014. We recorded patient demographics and clinical data, including the blood pressure measurements, arm circumference and the manufacturer of the home blood pressure monitor. The average of BP measurements performed with the home blood pressure monitor, were compared to those with the mercury sphygmomanometer. We defined accuracy based on a difference of 5 mm Hg in the blood pressure values between the home monitor and mercury sphygmomanometer readings. The two methods were compared using a Bland-Altman plot and a student's t-test. RESULTS: The study included 210 patients. The mean age of the study population was 67 years and 61% was men. The average mid-arm circumference was 32.2 cms. 30% and 32% of the home BP monitors reported a mean systolic and diastolic BP values, respectively, different from the mercury measurements by 5 mm Hg or more. There was no significant difference between the monitors that were accurate versus those that were not when grouped according to the patient characteristics, cuff size or the brand of the home monitor. CONCLUSIONS: An important proportion of home blood pressure monitors used by patients seen in our nephrology clinic were inaccurate. A re-validation of the accuracy and safety of the devices already in use is prudent before relying on these measurements for clinical decisions. PMID- 27249057 TI - Acute Corneal Hydrops in Children with Primary Infantile Glaucoma: A Report of 31 Cases over 23 Years at the LVPEI. AB - PURPOSE: Relatively little data exist regarding the outcomes of children with primary infantile glaucoma presenting with acute corneal hydrops. The aim of our study was to determine the surgical outcome of children of infantile glaucoma who presented with acute corneal hydrops. METHODS: In total, 38 eyes of 31 consecutive children of infantile glaucoma presented with acute corneal hydrops who underwent primary combined trabeculotomy-trabeculectomy (CTT) by a single surgeon from January 1990 to December 2012 at the LV Prasad Eye Institute (LVPEI), a tertiary eye care centre in Southern India were enrolled in this retrospective study. Primary outcome measures were intraocular pressure (IOP) control (IOP <= 16 mmHg under anaesthesia or IOP <= 21 mmHg without anaesthesia) and clearance of corneal edema. Secondary outcome measures were visual acuity (VA), corneal diameter, bleb appearance, intraoperative and postoperative complications. RESULTS: Mean age at presentation was 6.4 months (range, 2-11 months) and seven eyes (23%) had bilateral affliction. At presentation, all eyes (100%) had moderate to severe degree of corneal edema with a mean preoperative IOP of 25.6 +/-5.1 mmHg. Postoperatively, the IOP reduced to 12.0 +/- 3.8 mmHg (difference = -13.6, 95% CI = -15.7 to -11.5, t = -13.18, p<0.0001), and the percentage reduction in IOP was 53.05%. Preoperatively 83% of the eyes were on antiglaucoma medication, and postoperatively 2 eyes (5.3%) required 1 antiglaucoma medication for control of IOP. Preoperatively, corneal edema was present in all eyes and postoperatively it cleared in all of them. Significant myopic astigmatism was present in 28 eyes (74%), the commonest being compound myopic astigmatism (75%) followed by simple myopic astigmatism (21%). Normal VA (best-corrected VA; BCVA >= 20/60) was achieved in 44.4% of the eyes and 22.2% eyes had low vision (BCVA, <20/60 to 20/400). Complete success (IOP control and clearance of corneal oedema) was obtained in 94.7% eyes. There were no significant intraoperative or postoperative complications. Two thirds of the patients showed low, elevated functional filtering bleb. No patient had any bleb leak, blebitis or bleb related endophthalmitis. The median follow-up was 36 months (range 2-228 months). CONCLUSIONS: Primary CTT is safe and effective in controlling IOP, resulting in complete clearance of corneal edema with modest visual improvement in children of infantile glaucoma presenting with acute corneal hydrops. The outcome of the study will have a positive impact on counseling the parents preoperatively. PMID- 27249058 TI - How Criterion Scores Predict the Overall Impact Score and Funding Outcomes for National Institutes of Health Peer-Reviewed Applications. AB - Understanding the factors associated with successful funding outcomes of research project grant (R01) applications is critical for the biomedical research community. R01 applications are evaluated through the National Institutes of Health (NIH) peer review system, where peer reviewers are asked to evaluate and assign scores to five research criteria when assessing an application's scientific and technical merit. This study examined the relationship of the five research criterion scores to the Overall Impact score and the likelihood of being funded for over 123,700 competing R01 applications for fiscal years 2010 through 2013. The relationships of other application and applicant characteristics, including demographics, to scoring and funding outcomes were studied as well. The analyses showed that the Approach and, to a lesser extent, the Significance criterion scores were the main predictors of an R01 application's Overall Impact score and its likelihood of being funded. Applicants might consider these findings when submitting future R01 applications to NIH. PMID- 27249059 TI - Correction: Modeling Reef Fish Biomass, Recovery Potential, and Management Priorities in the Western Indian Ocean. AB - [This corrects the article DOI: 10.1371/journal.pone.0154585.]. PMID- 27249060 TI - Ischemic Heart Disease Incidence in Relation to Fine versus Total Particulate Matter Exposure in a U.S. Aluminum Industry Cohort. AB - Ischemic heart disease (IHD) has been linked to exposures to airborne particles with an aerodynamic diameter <2.5 MUm (PM2.5) in the ambient environment and in occupational settings. Routine industrial exposure monitoring, however, has traditionally focused on total particulate matter (TPM). To assess potential benefits of PM2.5 monitoring, we compared the exposure-response relationships between both PM2.5 and TPM and incidence of IHD in a cohort of active aluminum industry workers. To account for the presence of time varying confounding by health status we applied marginal structural Cox models in a cohort followed with medical claims data for IHD incidence from 1998 to 2012. Analyses were stratified by work process into smelters (n = 6,579) and fabrication (n = 7,432). Binary exposure was defined by the 10th-percentile cut-off from the respective TPM and PM2.5 exposure distributions for each work process. Hazard Ratios (HR) comparing always exposed above the exposure cut-off to always exposed below the cut-off were higher for PM2.5, with HRs of 1.70 (95% confidence interval (CI): 1.11-2.60) and 1.48 (95% CI: 1.02-2.13) in smelters and fabrication, respectively. For TPM, the HRs were 1.25 (95% CI: 0.89-1.77) and 1.25 (95% CI: 0.88-1.77) for smelters and fabrication respectively. Although TPM and PM2.5 were highly correlated in this work environment, results indicate that, consistent with biologic plausibility, PM2.5 is a stronger predictor of IHD risk than TPM. Cardiovascular risk management in the aluminum industry, and other similar work environments, could be better guided by exposure surveillance programs monitoring PM2.5. PMID- 27249061 TI - Structure and Stability Studies of Pharmacologically Relevant S-Nitrosothiols: A Theoretical Approach. AB - Nowadays, S-nitrosothiols (RSNOs) represent a promising class of nitric oxide (NO) donors that could be successfully used as drugs to compensate the decrease of NO production that usually arises in conjunction with cardiovascular diseases. Nevertheless, notwithstanding their pharmacological interest, the structure stability relationship in RSNOs is still unclear, and this issue, together with the mechanism of NO donation in the physiological medium, deserves further investigation. As a first step forward in this direction, in this paper, the overall stability and structural preference of two pharmacologically relevant S nitrosothiol molecules were studied in detail by means of computational strategies. In particular, performing calculations in implicit solvent (water) on the S-nitroso-N-acetylpenicillamine and the S-nitroso-N-acetylcysteine and analyzing the noncovalent interactions networks of their most stable conformers, we observed that the structure and the stability of these molecules can be directly related to the formation of stabilizing hydrogen-bond and chalcogen chalcogen intramolecular interactions. The obtained results represent the starting point for further investigations to be conducted also on larger RSNOs to shed further light on the role played by intra- and intermolecular interactions and by solvation effects in stabilizing this class of molecules. The obtained insights will be hopefully helpful to design new RSNO-based drugs characterized by an enhanced pharmacological potency. PMID- 27249062 TI - Two forms of self-criticism mediate differently the shame-psychopathological symptoms link. AB - OBJECTIVES: This study explored the relation between external shame, two types of self-criticism, and depressive, anxious and stress symptoms, in a clinical sample. Specifically, we set out to test whether the impact of external shame on such symptoms would be mediated by two forms of self-criticism. METHOD: A total of 279 patients (228 female and 51 male; mean age of 28.58) with axis I and II disorders recruited from several outpatients psychiatric services in Portugal completed the Other as Shamer Scale (OAS), the Forms of Self Criticizing/Attacking and Self-Reassuring Scale (FSCRS), and the Depression, Anxiety and Stress Scale (DASS-42). RESULTS: Self-criticism mediated in part the shame-psychopathological symptoms link, especially the hated self form. The alternative model where shame mediates the link between self-criticism and psychopathological symptoms was also significant. This result suggests that fear of being devalued in the minds of others has a significant impact on people's psychological well-being, and this effect can be partially explained by self criticism. CONCLUSIONS: This study highlights that inadequate self and hated self are separable types of self-criticism, because they show different patterns of association with psychopathology. Shame and self-criticism appear to mutually enhance one another, and both are associated with psychopathological symptoms. External shame and self-criticism should be a target in treatment. PRACTITIONER POINTS: External shame and self-criticism are associated with depressive, anxious, and stress symptoms, in a clinical sample. Self-criticism, especially hatred for the self, mediates the shame-psychopathological symptoms link. Shame and self-criticism should be addressed in therapeutic interventions targeting the reduction of depression, anxiety, and stress symptoms. PMID- 27249063 TI - Control of Urban Zika Vectors: Should We Return to the Successful PAHO/WHO Strategy? PMID- 27249064 TI - Acylated Carrageenan Changes the Physicochemical Properties of Mixed Enzyme-Lipid Ultrathin Films and Enhances the Catalytic Properties of Sucrose Phosphorylase Nanostructured as Smart Surfaces. AB - Control over the catalytic activity of enzymes is important to construct biosensors with a wide range of detectability and higher stability. For this, immobilization of enzymes on solid supports as nanostructured films is a current approach that permits easy control of the molecular architecture as well as tuning of the properties. In this article, we employed acylated carrageenan (AC) mixed with phospholipids at the air-water interface to facilitate the adsorption of the enzyme sucrose phosphorylase (SP). AC stabilized the adsorption of SP at the phospholipid monolayer, as detected by tensiometry, by which thermodynamic parameters could be inferred from the surface pressure-area isotherm. Also, infrared spectroscopy applied in situ over the monolayer showed that the AC phospholipid system not only permitted the enzyme to be adsorbed but also helped conserve its secondary structure. The mixed monolayers were then transferred onto solid supports as Langmuir-Blodgett (LB) films and investigated with transfer ratio, quartz crystal microbalance, fluorescence spectroscopy, and atomic force microscopy. The enzyme activity of the LB film was then determined, revealing that although there was an expected reduction in activity in relation to the homogeneous environment the activity could be better preserved after 1 month, revealing enhanced stability. PMID- 27249065 TI - Low Temperature Induced Changes in Citrate Metabolism in Ponkan (Citrus reticulata Blanco cv. Ponkan) Fruit during Maturation. AB - Citrate is the most important organic acid in citrus fruit, and its concentration in fruit cells is regulated mainly by the balance between synthesis and degradation. Ponkan (Citrus reticulate Blanco cv. Ponkan) is one of the major citrus cultivars grew in China, and the fruit are picked before fully mature to avoid bad weather. Greenhouse production is widely used to prolong the maturation period and improve the quality of Ponkan fruit by maintaining adequate temperature and providing protection from adverse weather. In this research, Ponkan fruit cultivated in either a greenhouse or open field were used to investigate differences in the expression of genes related to citrate metabolism during maturation in the two environments. The citrate contents were higher in open field fruit, and were mainly correlated with expressions of CitPEPCs, CitCSs, CitAco3 and CitGAD4, which were significantly increased. In addition, the impacts of low temperature (LT) and water stress (WS) on citrate metabolism in Ponkan were investigated during fruit maturation. The citrate contents in LT fruit were significantly increased, by between 1.4-1.9 fold, compared to the control; it showed no significant difference in fruit with water stress treatment compared to the control fruit. Furthermore, the expressions of CitPEPCs, CitCSs, CitAco3 and CitGAD4 were significantly increased in response to LT treatment, but showed no significant difference in WS compared to the control fruit. Thus, it can be concluded that low temperature may be the main factor influencing citrate metabolism during maturation in Ponkan fruit. PMID- 27249066 TI - Effects of Ripasudil Hydrochloride Hydrate Instillation on Pupil Dynamics. AB - PURPOSE: We investigated the effects of instillation of ripasudil hydrochloride hydrate (GLANATEC(r)) on pupil dynamics. MATERIALS AND METHODS: Fourteen healthy participants (mean age: 30 years), who had no ophthalmic diseases other than refractive error, were enrolled in this study. A single dose of GLANATEC(r) was instilled into the left eye only. The pupillary response was measured before and 30 and 120 min after instillation; we also measured intraocular pressure (IOP) at the same time points. RESULTS: The IOP in the left eye was significantly lower at both 30 (p < 0.05) and 120 (p < 0.01) min after instillation than at baseline, whereas that in the right eye was not significantly different from baseline at either of the measured post-instillation time points. In contrast, the pupillary response did not significantly differ between the three time points. CONCLUSIONS: A single instillation of low concentration GLANATEC(r) may have no effect on pupil diameter and pupillary response. PMID- 27249067 TI - Fulminant hepatitis B as a result of reactivation in hematologic patient after rituximab therapy. PMID- 27249068 TI - Genetic detection of hantaviruses in rodents, Albania. AB - In order to have a first insight into the epidemiology of hantaviruses in Albania, 263 small mammals (248 rodents, 15 insectivores) were captured in 352 locations in 29 districts and tested for hantavirus infection. Dobrava-Belgrade virus (DOBV) was detected in 10 of 148 (6.7%) Apodemus flavicollis rodents. DOBV positive A. flavicollis were detected in six districts (Diber, Korce, Kolonje, Librazhd, Pogradec, and Vlore). The obtained nucleotide sequences were highly similar to each other and to DOBV sequences from northwestern Greece. Understanding the epidemiology of hantaviruses and identifying the endemic foci enables the public health strategies to minimize the risk of human infection. J. Med. Virol. 88:1309-1313, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27249069 TI - Functional analysis of human cytomegalovirus UL/b' region using SCID-hu mouse model. AB - Human cytomegalovirus (HCMV) attenuated strains, Towne, and AD169, differ from prototypic pathogenic strains, such as Toledo, in that they are missing a ~15-kb segment in the UL/b' region. In contrast to the attenuated strains, Toledo can replicate in human tissue implants in SCID (SCID-hu) mice. Thus, this model provides a unique in vivo system to study the mechanism of viral pathogenesis. Twenty-two ORFs have been annotated in the UL/b' region, including tissue-tropic genes encoded in a pentameric gH/gl complex. To differentiate the role of the pentameric gH/gl complex versus the functions of other ORFs in the 15-kb region in supporting viral growth in vivo, a series of recombinant viral strains were constructed and their ability to replicate in SCID-hu mice was tested. The mutations in the Towne and AD169 strains were repaired to restore their pentameric gH/gl complex and it was found that these changes did not rescue their inability to replicate in the SCID-hu mice. Subsequently four deletion viruses (D1, D2, D3, and D4) in the 15-kb region from the Toledo strain were created. It was demonstrated that D2 and D3 were able to grow in SCID-hu mice, while D1 and D4 were not viable. Interestingly, co-infection of the implant with the D1 and D4 viruses could compensate their respective growth defect in vivo. The results demonstrated that rescuing viral epithelial tropism is not sufficient to revert the attenuation phenotype of AD169 or Towne, and pathogenic genes are located in the segments missing in D1 and D4 viruses. J. Med. Virol. 88:1417-1426, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27249070 TI - Preparation of an inoculum of Gluconacetobacter xylinus without mutants in shaken culture. AB - AIMS: A high-quality inoculum of Gluconacetobacter xylinus is important to produce bacterial cellulose (BC), a versatile biomaterial. This work aims to develop a method of preparing an inoculum of this bacterium with high cell density and without mutants. METHODS AND RESULTS: Inocula of G. xylinus ACCC 10220 without and with cellulase or carboxymethyl cellulose (CMC) were prepared in shaken culture. BC pellets and BC-negative mutants were present in the inoculum without additives but absent in the inoculum with additives. Based on BC weights statically produced in fresh BC-producing media initiated by different seed culture, the 24-h-shaken inoculum with 1.50% (w/v) CMC was the best because of high biomass and absence of mutants. The BC weights in fresh media inoculated by the 96-h-static inoculum and 24-h-shaken CMC inoculum at 7% (v/v) were 0.70 and 1.05 g l(-1) , respectively, implying significant difference (P < 0.01) in BC weights. However, structure properties of the two BC samples, including the crystallinity index, mass fraction of cellulose Ialpha , degree of polymerization (DP) and micromorphology were slightly different. CONCLUSIONS: The 24-h-shaken CMC inoculum was the most suitable for a starter culture of BC. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel method of preparing G. xylinus inoculum in shaken culture was developed, featuring high biomass, absence of mutants and no BC entanglements. Cellulase or CMC added into the medium completely suppressed mutation of G. xylinus, and CMC facilitated to form colloidal BC with the low DP in shaken culture, indicating less BC stress to cells. These findings suggested the mutation could be induced by BC stress, and not by shear stress commonly accepted. PMID- 27249071 TI - On the Vapor Trail: Examining the Chemical Content of E-Cigarette Flavorings. PMID- 27249073 TI - Development and exploratory testing of a school-based educational program for healthy life behaviors among fifth grade children in South Korea. AB - AIM: The purpose of this study was to develop an educational program to promote healthy life behaviors and to evaluate its potential effects on the health practices of fifth grade elementary school children. METHODS: The program, which consisted of six categories (daily life and health, disease prevention and management, prevention of drug misuse and overuse, sexuality and health, mental health, and injury prevention and first aid), was developed based on the ADDIE model. A pretest-post-test, one-group, quasi-experimental design was used with 85 elementary school students who voluntarily participated in the program. RESULTS: A school-based educational program, called the "Six Kid Keys," referring to the six categories of healthy life behaviors, was developed. Significant pre-post differences in two of the six healthy life behavior categories (disease prevention and management, injury prevention and first aid) were found. CONCLUSION: A school-based intervention that was aimed at changing habits related to healthy life behaviors could be effective for elementary school children. PMID- 27249072 TI - GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas. AB - OBJECTIVE: Recent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients. METHODS: We evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases. RESULT: GATA3-positive expression was significantly associated with a higher mitotic count (P < 0.0001). Disease-free survival (DFS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0104). Overall survival (OS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0006). GATA3-positive expression was significantly associated with shorter DFS in both univariate analysis (hazard ratio [HR], 2.719; P = 0.012) and multivariate analysis (HR, 2.711; P = 0.014). GATA3-positive expression was also significantly associated with worse OS in both univariate analysis (HR, 5.730; P = 0.0007) and multivariate analysis (HR, 5.789; P = 0.0008). CONCLUSION: These results indicate that GATA3 is an independent prognostic factor and suggest that evaluation of GATA3 expression might enable more effective clinical follow-up using prognostic stratification of STS patients. PMID- 27249074 TI - The course of suicide risk following traumatic injury. AB - OBJECTIVE: Although traumatic injuries affect millions of patients each year and increase risk for psychiatric disorder, no evidence currently exists regarding associated suicidal risk. This study reports a longitudinal investigation of suicidal risk in the 2 years after traumatic injury. METHODS: A prospective design cohort study was conducted in 4 major trauma hospitals across Australia. A total of 1,129 traumatically injured patients were assessed during hospital admission between April 2004 and February 2006 and were followed up at 3 months (88%), 12 months (77%), and 24 months (72%). Lifetime psychiatric disorder was assessed in hospital using the Mini-International Neuropsychiatric Interview, version 5.5, which was also used to assess the prevalence of suicidality, psychiatric disorder, and exposure to adverse life events at 3, 12, and 24 months after traumatic injury. RESULTS: Approximately 6% of patients reported moderate/high suicidal risk at each assessment. At each assessment, half of suicidal patients reported no suicidal risk at the previous assessment. Suicidality at 24 months was predicted by current pain levels (odds ratio [OR] = 1.16; 95% CI, 1.09-1.23), recent life events (OR = 1.30; 95% CI,1.17-1.44), and current psychiatric disorder (OR = 17.07; 95% CI, 7.03-41.42), whereas only 36.6% of suicidal patients had consulted a mental health professional in the previous month, and 66.2% had consulted a primary care physician. CONCLUSIONS: Suicidal risk affects a significant proportion of patients who experience a traumatic injury, and the risk for suicide fluctuates markedly in the initial years following the injury. Primary care physicians need to be trained to assess for suicidal risk in the initial years after a traumatic injury. PMID- 27249075 TI - Benzodiazepine use and risk of mortality among patients with schizophrenia: a retrospective longitudinal study. AB - OBJECTIVE: This study examined the association between benzodiazepine use alone or in combination with antipsychotics and risk of mortality in patients with schizophrenia. METHODS: A retrospective longitudinal analysis was performed using Medicaid claims data merged with death certificate data for 18,953 patients (aged 18-58 years) with ICD-9-diagnosed schizophrenia followed from July 1, 2006, to December 31, 2013. Cox proportional hazard analyses were used to estimate the risk of all-cause mortality associated with benzodiazepine use; adjustment was made for a wide array of fixed and time-varying confounders, including demographics, psychiatric and medical comorbidities, and other psychotropic medications. RESULTS: Of the 18,953 patients diagnosed with schizophrenia, 13,741 (72.5%) were not prescribed a benzodiazepine, 3,476 (18.3%) were prescribed benzodiazepines in the absence of antipsychotic medication, and 1,736 (9.2%) were prescribed benzodiazepines in combination with antipsychotics. Controlling for a wide array of demographic and clinical variables, the hazard of mortality was 208% higher for patients prescribed benzodiazepines without an antipsychotic (HR = 3.08; 95% CI, 2.63-3.61; P < .001) and 48% higher for patients prescribed benzodiazepines in combination with antipsychotics (HR = 1.48; 95% CI, 1.15-1.91; P = .002). Benzodiazepine-prescribed patients were at greater risk of death by suicide and accidental poisoning as well as from natural causes. CONCLUSIONS: Benzodiazepine use is associated with increased mortality risk in patients with schizophrenia after adjusting for a wide range of potential confounders. Given unproven efficacy, physicians should exercise caution in prescribing benzodiazepines to schizophrenic patients. PMID- 27249076 TI - Introduction. AB - Welcome to the Early Career Psychiatrists section of the Journal of Clinical Psychiatry! This month, we highlight the work of individuals who are in the early phase of an academic psychiatry career. We present 4 articles on a diverse array of topics, including 2 on posttraumatic stress disorder (PTSD). The treatment of PTSD is of paramount importance to improving the mental health of those around the world who develop chronic stress after exposure to violence and trauma. PMID- 27249077 TI - Open-Label trial on the effects of memantine in adults with obsessive-compulsive disorder after a single ketamine infusion. PMID- 27249078 TI - Safety and efficacy of electroconvulsive therapy for depression in the presence of deep brain stimulation in obsessive-compulsive disorder. PMID- 27249079 TI - Cannabis and neuropsychiatry, 1: benefits and risks. AB - Cannabis is popularly believed to be a relatively benign substance. Cannabis is also considered to have potential medical benefits, and medical marijuana has been legislated in many parts of the world. However, a recent meta-analysis found that cannabinoids were associated with only modest benefits for chemotherapy related nausea and vomiting, small and inconsistent benefits for pain and spasticity, and inconclusive benefits for other indications such as improvement of appetite and weight, reduction in tic severity, and improvement of mood or sleep. On the flip side, cannabinoids and cannabis have acute and long-term adverse effects. In randomized controlled trials, cannabinoids increase the risk of total adverse events, serious adverse events, and dropout due to adverse events. Cannabis impairs cognition, and driving after cannabis use is associated with an increased risk of traffic accidents, including fatal accidents. Long-term cannabis use may lead to dependence, respiratory conditions, psychosis, and possibly cancer, as well. Cannabis use during pregnancy may compromise certain pregnancy outcomes such as fetal growth, and use during adolescence may compromise neurodevelopment, social adjustment, and vocational success. The composition and bioavailability of cannabis vary across preparations of the substance and routes of administration; this limits the ability to generalize the findings of studies. The findings of older research may no longer apply to current strains of cannabis that are higher in psychotogenic content. It is important for medical professionals and the lay public to understand the limitations of the efficacy data and the seriousness of the risks associated with cannabis use in medical and recreational contexts. PMID- 27249080 TI - Doxazosin XL reduces symptoms of posttraumatic stress disorder in veterans with PTSD: a pilot clinical trial. AB - BACKGROUND: Serotonin and norepinephrine reuptake inhibitors are effective first line agents for the treatment of posttraumatic stress disorder (PTSD), but treatment is associated with a range of side effects that limit treatment adherence. Prazosin, an alpha1-noradrenergic antagonist with a half-life of roughly 2-3 hours, has shown promise in the treatment of sleep disturbance and nightmares. Doxazosin extended release (XL) is also an alpha1-noradrenergic antagonist but with a half-life of approximately 15-19 hours. METHODS: We conducted a double-blind, placebo-controlled, within-subjects trial to characterize the impact of doxazosin XL on PTSD symptoms. Participants (N = 8) were diagnosed using DSM-IV criteria. They completed the study twice, once during treatment with doxazosin XL and once during treatment with matched placebo, with a 2-week washout separating the 2 episodes. Doxazosin XL was titrated from 4 mg/d to 16 mg/d over 12 days. After 4 days of treatment at 16 mg/d or the equivalent number of placebo capsules, PTSD symptoms were assessed using the Clinician Administered PTSD Scale (CAPS17) and the PTSD Checklist-Military version (PCL-M). Repeated measures analysis of variance were used to evaluate effects of treatment, time, and treatment * time. This study was run from November 20, 2013, to June 31, 2014. RESULTS: Doxazosin XL treatment was associated with a nonsignificant treatment * time reduction in ratings on the CAPS hyperarousal subscale (P < .10) (but not on the CAPS Total score) and with significant treatment * time reductions in PCL-M ratings (P = .002). CONCLUSIONS: Doxazosin XL may be an effective alternative to prazosin for the treatment of some PTSD symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:NCT02308202. PMID- 27249081 TI - Comparative risk of seizure with use of first- and second-generation antipsychotics in patients with schizophrenia and mood disorders. AB - OBJECTIVE: To compare the risk of antipsychotic-related seizure (ARS) by identifying seizures first diagnosed within 12 months after starting new antipsychotics, using a 12-year total population health claims database from Taiwan. METHODS: Seizure events were identified through emergency department visits or hospitalization with a diagnosis of convulsion (ICD-9-CM: 780.3) or epilepsy (ICD-9-CM: 345). Subjects had an ICD-9-CM diagnosis of schizophrenia, bipolar disorders, or major depressive disorders. Incidence rates of ARS were calculated by person-years of exposure. The ARS risk, adjusted for patient characteristics and medical conditions, of individual antipsychotics versus risperidone was examined by high-dimensional propensity score stratification analyses, followed by sensitivity analyses. RESULTS: The overall 1-year incidence rate of ARS was 9.6 (95% CI, 8.8-10.4) per 1,000 person-years (550 ARS events among 288,397 new antipsychotic users). First-generation antipsychotics were marginally associated with a higher ARS risk than second-generation antipsychotics (adjusted hazard ratio [aHR] = 1.34; 95% CI, 0.99-1.81; P = .061). Most antipsychotics, first- or second-generation, had comparable ARS risks versus risperidone. Notably, clozapine (aHR = 3.06; 95% CI, 1.40-6.71), thioridazine (aHR = 2.90; 95% CI, 1.65-5.10), chlorprothixene (aHR = 2.60; 95% CI, 1.04-6.49), and haloperidol (aHR = 2.34; 95% CI, 1.48-3.71) had higher ARS risks than risperidone, whereas aripiprazole (aHR = 0.41; 95% CI, 0.17-1.00; P = .050) had a marginally lower ARS risk. Sensitivity analyses largely confirmed such findings. CONCLUSIONS: Higher vigilance for ARS is warranted during use of clozapine, chlorprothixene, thioridazine, and haloperidol. The possible lower ARS risk associated with aripiprazole can be clinically significant but needs to be confirmed by larger-scale systematic studies. The comparative ARS risks of antipsychotics supplement empirical knowledge for making judicious choices in prescribing antipsychotics. PMID- 27249082 TI - Can development of PTSD be prevented after acute trauma? PMID- 27249083 TI - The incidence of seizures with antipsychotics. PMID- 27249084 TI - Benzodiazepine safety: mortality risk or multiple chronic disease comorbidity? PMID- 27249085 TI - How many treatments before clozapine? medication choices across the spectrum of treatment resistance in schizophrenia. PMID- 27249086 TI - Gene expression profiling of the xMHC region reveals 9 candidate genes in schizophrenia. PMID- 27249087 TI - Sudden cardiac death related to antipsychotics: beyond the long QT syndrome hypothesis. PMID- 27249088 TI - Why is mechanism of action important in antidepressant treatment? AB - Antidepressants are one of the most common treatment strategies for patients diagnosed with major depressive disorder (MDD). However, antidepressant medications have different mechanisms of action that can theoretically and in practice affect how patients respond. Clinicians should assess their patients' symptoms and response to medication at every visit to determine whether or not the treatment is fully effective. Here, follow the case of Maria, a 42-year-old teacher who is experiencing her first depressive episode. PMID- 27249089 TI - Impact of anxious symptoms and comorbid anxiety disorders on functional impairment in depressed patients. AB - Patients with depression may have unrecognized anxiety symptoms or comorbid anxiety disorders that hinder their ability to function and their response to treatment. Patients with both depressive and anxious symptoms may be more sensitive to medication adverse effects and require lower starting doses of antidepressants than those with only depression. Regular monitoring of symptoms and functioning should include the use of rating scales to help identify areas of need. Novel antidepressants and augmentation strategies may be necessary to help patients achieve recovery. PMID- 27249090 TI - Early onset of response with selective serotonin reuptake inhibitors in obsessive compulsive disorder: a meta-analysis. AB - OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are recommended as the first-line pharmacologic treatment for obsessive-compulsive disorder (OCD). SSRI response is thought to be delayed in OCD, even more so than in major depression. We conducted a meta-analysis to examine the trajectory of treatment response to SSRIs and how this trajectory is modulated by dosage. DATA SOURCES: PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on May 22, 2013, for randomized, placebo-controlled SSRI trials in OCD with the search terms "serotonin uptake inhibitors" [MeSH] OR "serotonin uptake inhibitors" [Pharmacologic Action] AND "obsessive-compulsive disorder" [MeSH]. There were no language limitations on the search. STUDY SELECTION: Randomized, placebo controlled trials that examined the efficacy of SSRIs in the treatment of adults with OCD and utilized the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as an outcome were selected. DATA EXTRACTION: We extracted weekly symptom data from randomized, placebo-controlled trials of SSRIs for the treatment of adults with OCD in order to characterize the trajectory of pharmacologic response. Our primary outcome was weighted mean difference on the Y-BOCS of SSRI treatment compared to placebo. We used the PROC MIXED procedure in SAS to examine 6 possible models of SSRI response. Interaction terms were utilized to examine the effect of dose, individual agent, and year of publication on SSRI response. RESULTS: The meta-analysis included 17 trials of SSRIs including 3,276 subjects. A statistically significant benefit of SSRIs compared to placebo was seen within 2 weeks after the start of treatment (weighted mean difference = -0.91 [95% CI, 0.54 to -1.28], P < .001). A logarithmic response curve, indicating decreasing symptom improvement over time, provided the best fit for the trajectory of OCD symptom improvement. A significantly greater response was associated with using higher doses of SSRIs (P < .0001). CONCLUSIONS: These results suggest that the greatest incremental treatment gains in OCD are seen early on in SSRI treatment. This is consistent with a previous meta-analysis examining time course of SSRI action in major depressive disorder and contrasts with the widely held belief that SSRI response in OCD is delayed. PMID- 27249091 TI - Age at the time of exposure to trauma modulates the psychopathological profile in patients with early psychosis. AB - OBJECTIVE: To examine the potential differential impact of childhood trauma, according to the age at the time of exposure, on the psychopathological profile of patients with early psychosis treated in a specialized 3-year program during the early phase of the disease. METHODS: 196 subjects with early psychosis aged 18-35 years were followed up prospectively over 36 months of treatment between 2004 and 2010. Patients who had faced at least 1 experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) were classified according to age at the time of the first exposure (early trauma: before 12 years of age; late trauma: from age 12 through 16 years) and then compared with unexposed patients (nontrauma). The level of symptoms was assessed using the Positive and Negative Syndrome Scale, the Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale. RESULTS: Exposure to 1 or more forms of trauma before 16 years of age was present in 31.63% of patients. Comparisons over the 3 years of treatment with the nontrauma patients revealed that (1) patients with early trauma showed consistently higher levels of positive (P = .006), depressive (P = .001), manic (P = .006), and negative (P = .029) symptoms and (2) patients with late trauma showed only more negative symptoms (P = .029). CONCLUSIONS: These results suggest that the age at the time of exposure to trauma has a modulating effect on symptoms in patients with early psychosis. Various biological and psychological hypotheses can be proposed to explain this observation, and they need to be investigated in an experimental setting in order to develop therapeutic avenues. PMID- 27249092 TI - Demographic variables, design characteristics, and effect sizes of randomized, placebo-controlled, monotherapy trials of major depressive disorder and bipolar depression. AB - OBJECTIVE: The aim of this work is to compare the efficacy of pharmacologic agents for the treatment of major depressive disorder (MDD) and bipolar depression. DATA SOURCES: MEDLINE/PubMed databases were searched for studies published in English between January 1980 and September 2014 by cross-referencing the search term placebo with each of the antidepressant agents identified and with bipolar. The search was supplemented by manual bibliography review. STUDY SELECTION: We selected double-blind, randomized, placebo-controlled trials of antidepressant monotherapies for the treatment of MDD and of oral drug monotherapies for the treatment of bipolar depression. 196 trials in MDD and 19 trials in bipolar depression were found eligible for inclusion in our analysis. DATA EXTRACTION: Data were extracted by one of the authors and checked for accuracy by a second one. Data extracted included year of publication, number of patients randomized, probability of receiving placebo, duration of the trial, baseline symptom severity, dosing schedule, study completion rates, and clinical response rates. RESULTS: Response rates for drug versus placebo in trials of MDD and bipolar depression were 52.7% versus 37.5% and 54.7% versus 40.5%, respectively. The random-effects meta-analysis indicated that drug therapy was more effective than placebo in both MDD (risk ratio for response = 1.373; P < .001) and bipolar depression (risk ratio = 1.257; P < .001) trials. The meta regression analysis suggested a statistically significant difference in the risk ratio of responding to drug versus placebo between MDD and bipolar depression trials in favor of MDD (P = .008). CONCLUSIONS: Although a statistically significantly greater treatment effect size was noted in MDD relative to bipolar depression studies, the absolute magnitude of the difference was numerically small. Therefore, the present study suggests no clinically significant differences in the overall short-term efficacy of pharmacologic monotherapies for MDD and bipolar depression. PMID- 27249093 TI - Impact of electrocoagulation of soluble microbial products on membrane fouling at different volatile suspended solids' concentrations. AB - This research had two objectives: (1) to study the combined effect of volatile suspended solids (VSS) and soluble microbial product (SMP) on membrane fouling in an attempt to explain the discrepancies of previous studies and (2) to investigate the feasibility of reducing SMP impact on membrane fouling rate by electrocoagulation. Electrocoagulation successfully removed up to 55% and 90% of protein and polysaccharides, respectively, which resulted in a substantial reduction of membrane fouling rate (four times less). The results showed that at a comparable VSS concentration, membrane fouling increased with an increase in SMP. For example, for the same magnitude of VSS, membrane fouling rate was four times higher as the concentration of SMP tripled. Higher VSS concentrations were not directly responsible for higher fouling rates unless there was an increase in the SMP concentration. It was concluded that the correlation of membrane fouling with VSS alone is misleading unless accompanied with SMP concentration. Statistical analysis demonstrated that VSS impact on membrane fouling was not significant when it was considered as a single independent variable. The most accurate prediction of the membrane fouling was built by multiple regression model based on a quadratic VSS and linear SMP as independent variables. PMID- 27249094 TI - Zika Virus Infection and Surgery: What Should We Be Concerned About? PMID- 27249095 TI - Drugs for multiple sclerosis. PMID- 27249096 TI - Pimavanserin (Nuplazid) for Parkinson's disease psychosis. PMID- 27249097 TI - Alternatives to fluoroquinolones. PMID- 27249098 TI - In brief: new indications for secukinumab (Cosentyx). PMID- 27249099 TI - In brief: liposomal irinotecan (Onivyde) for pancreatic cancer. PMID- 27249100 TI - In brief: trifluridine/tipiracil (Lonsurf) for metastatic colorectal cancer. PMID- 27249101 TI - Ligand-Induced Stabilization of a Duplex-like Architecture Is Crucial for the Switching Mechanism of the SAM-III Riboswitch. AB - Riboswitches are structured RNA motifs that control gene expression by sensing the concentrations of specific metabolites and make up a promising new class of antibiotic targets. S-Adenosylmethionine (SAM)-III riboswitch, mainly found in lactic acid bacteria, is involved in regulating methionine and SAM biosynthetic pathways. SAM-III riboswitch regulates the gene expression by switching the translation process on and off with respect to the absence and presence of the SAM ligand, respectively. In this study, an attempt is made to understand the key conformational transitions involved in ligand binding using atomistic molecular dynamics (MD) simulations performed in an explicit solvent environment. G26 is found to recognize the SAM ligand by forming hydrogen bonds, whereas the absence of the ligand leads to opening of the binding pocket. Consistent with experimental results, the absence of the SAM ligand weakens the base pairing interactions between the nucleobases that are part of the Shine-Dalgarno (SD) and anti-Shine-Dalgarno (aSD) sequences, which in turn facilitates recognition of the SD sequence by ribosomes. Detailed analysis reveals that a duplex-like structure formed by nucleotides from different parts of the RNA and the adenine base of the ligand is crucial for the stability of the completely folded state in the presence of the ligand. Previous experimental studies have shown that the SAM-III riboswitch exists in equilibrium between the unfolded and partially folded states in the absence of the ligand, which completely folds upon binding of the ligand. Comparison of the results presented here to the available experimental data indicates the structures obtained using the MD simulations resemble the partially folded state. Thus, this study provides a detailed understanding of the fully and partially folded structures of the SAM-III riboswitch in the presence and absence of the ligand, respectively. This study hypothesizes a dual role for the SAM ligand, which facilitates conformational switching between partially and fully folded states by forming a stable duplex-like structure and strengthening the interactions between SD and aSD nucleotides. PMID- 27249103 TI - Emissions from oil and gas operations in the United States. PMID- 27249102 TI - Epigenetic age predictions based on buccal swabs are more precise in combination with cell type-specific DNA methylation signatures. AB - Aging is reflected by highly reproducible DNA methylation (DNAm) changes that open new perspectives for estimation of chronological age in legal medicine. DNA can be harvested non-invasively from cells at the inside of a person's cheek using buccal swabs - but these specimens resemble heterogeneous mixtures of buccal epithelial cells and leukocytes with different epigenetic makeup. In this study, we have trained an age predictor based on three age-associated CpG sites (associated with the genesPDE4C, ASPA, and ITGA2B) for swab samples to reach a mean absolute deviation (MAD) between predicted and chronological age of 4.3 years in a training set and of 7.03 years in a validation set. Subsequently, the composition of buccal epithelial cells versus leukocytes was estimated by two additional CpGs (associated with the genes CD6 and SERPINB5). Results of this "Buccal-Cell-Signature" correlated with cell counts in cytological stains (R2 = 0.94). Combination of cell type-specific and age-associated CpGs into one multivariate model enabled age predictions with MADs of 5.09 years and 5.12 years in two independent validation sets. Our results demonstrate that the cellular composition in buccal swab samples can be determined by DNAm at two cell type specific CpGs to improve epigenetic age predictions. PMID- 27249104 TI - Emissions from oil and gas operations in the United States and their air quality implications. AB - The energy supply infrastructure in the United States has been changing dramatically over the past decade. Increased production of oil and natural gas, particularly from shale resources using horizontal drilling and hydraulic fracturing, made the United States the world's largest producer of oil and natural gas in 2014. This review examines air quality impacts, specifically, changes in greenhouse gas, criteria air pollutant, and air toxics emissions from oil and gas production activities that are a result of these changes in energy supplies and use. National emission inventories indicate that volatile organic compound (VOC) and nitrogen oxide (NOx) emissions from oil and gas supply chains in the United States have been increasing significantly, whereas emission inventories for greenhouse gases have seen slight declines over the past decade. These emission inventories are based on counts of equipment and operational activities (activity factors), multiplied by average emission factors, and therefore are subject to uncertainties in these factors. Although uncertainties associated with activity data and missing emission source types can be significant, multiple recent measurement studies indicate that the greatest uncertainties are associated with emission factors. In many source categories, small groups of devices or sites, referred to as super-emitters, contribute a large fraction of emissions. When super-emitters are accounted for, multiple measurement approaches, at multiple scales, produce similar results for estimated emissions. Challenges moving forward include identifying super-emitters and reducing their emission magnitudes. Work done to date suggests that both equipment malfunction and operational practices can be important. Finally, although most of this review focuses on emissions from energy supply infrastructures, the regional air quality implications of some coupled energy production and use scenarios are examined. These case studies suggest that both energy production and use should be considered in assessing air quality implications of changes in energy infrastructures, and that impacts are likely to vary among regions. IMPLICATIONS: The energy supply infrastructure in the United States has been changing dramatically over the past decade, leading to changes in emissions from oil and natural gas supply chain sources. In many source categories along these supply chains, small groups of devices or sites, referred to as super-emitters, contribute a large fraction of emissions. Effective emission reductions will require technologies for both identifying super-emitters and reducing their emission magnitudes. PMID- 27249105 TI - Greenhouse gas emissions estimation from proposed El Fukhary Landfill in the Gaza Strip. AB - Landfills throughout the world are contributing to the global warming problem. This is due to the existence of the most important greenhouse gases (GHG) in landfill gas (LFG); namely, methane (CH4) and carbon dioxide (CO2). The aim of this paper is quantifying the total potential emissions, as well as the variation in production with time of CH4 from a proposed landfill (El Fukhary landfill) in the Gaza Strip, Palestine. Two different methods were adopted in order to quantify the total potential CH4 emissions; the Default methodology based on the intergovernmental panel on climate change (IPCC) 1996 revised guidelines and the Landfill Gas Emissions model (LandGEM V3.02) provided by the United States Environmental Protection Agency (EPA). The second objective of the study has been accomplished using the Triangle gas production model. The results obtained from both Default and LandGEM methods were found to be nearly the same. For 25 years of disposing MSW, El Fukhary landfill expected to have potential CH4 emissions of 1.9542 +/- 0.0037 *109 m3. Triangle model showed that the peak production in term of CH4 would occur in 2043; 28 years beyond the open year. Moreover, the model shows that 50 % of the gas will be produced approximately at the middle of the total duration of gas production. Proper control of Methane emissions from El Fukhary landfill is highly suggested in order to reduce the harmful effects on the environment. IMPLICATIONS: Although, GHG emissions are extensively discussed in the developed countries throughout the world, it has gained little concern in the developing countries because they are forced most of the time to put environmental concerns at the end of their priority list. The paper shows that developing countries have to start recognizing their fault and change their way of dealing with environmental issues especially GHG emissions (mainly Methane and carbon dioxide). The authors estimated the potential methane emissions from a proposed central landfill that has been approved to be built in Palestine, a country that is classified as a developing country. PMID- 27249106 TI - The Association Between Internal and External Measures of Training Load in Batsmen and Medium-Fast Bowlers During Net-Based Cricket Training. AB - PURPOSE: To examine the relationship between session rating of perceived exertion (sRPE) and measures of internal and external training load (TL) in cricket batsmen and medium-fast bowlers during net-based training sessions. METHODS: The internal (heart rate), external (movement demands, PlayerLoad), and technical (cricket-specific skills) loads of 30 male cricket players (age 21.2 +/- 3.8 y, height 1.82 +/- 0.07 m, body mass 79.0 +/- 8.7 kg) were determined from net-based cricket-training sessions (n = 118). The relationships between sRPE and measures of TL were quantified using Pearson product-moment correlations respective to playing position. Stepwise multiple-regression techniques provided key internal- and external-load determinants of sRPE in cricket players. RESULTS: Significant correlations were evident (r = -.34 to .87, P < .05) between internal and external measures of TL and sRPE, with the strongest correlations (r >= .62) for GPS-derived measures for both playing positions. In batsmen, stepwise multiple regression analysis revealed that 67.8% of the adjusted variance in sRPE could be explained by PlayerLoad and high-intensity distance (y = 27.43 + 0.81 PlayerLoad + 0.29 high-intensity distance). For medium-fast bowlers, 76.3% of the adjusted variance could be explained by total distance and mean heart rate (y = 101.82 + total distance 0.05 + HRmean - 0.48). CONCLUSION: These results suggest that sRPE is a valid method of reporting TL among cricket batsmen and medium-fast bowlers. Position-specific responses are evident and should be considered when monitoring the TL of cricket players. PMID- 27249109 TI - Why Is the X-Ray Tube Usually Located Underneath the Patient Instead of Above the Patient for Interventional Fluoroscopic Procedures? PMID- 27249108 TI - ATAC-seq on biobanked specimens defines a unique chromatin accessibility structure in naive SLE B cells. AB - Biobanking is a widespread practice for storing biological samples for future studies ranging from genotyping to RNA analysis. However, methods that probe the status of the epigenome are lacking. Here, the framework for applying the Assay for Transposase Accessible Sequencing (ATAC-seq) to biobanked specimens is described and was used to examine the accessibility landscape of naive B cells from Systemic Lupus Erythematosus (SLE) patients undergoing disease flares. An SLE specific chromatin accessibility signature was identified. Changes in accessibility occurred at loci surrounding genes involved in B cell activation and contained motifs for transcription factors that regulate B cell activation and differentiation. These data provide evidence for an altered epigenetic programming in SLE B cells and identify loci and transcription factor networks that potentially impact disease. The ability to determine the chromatin accessibility landscape and identify cis-regulatory elements has broad application to studies using biorepositories and offers significant advantages to improve the molecular information obtained from biobanked samples. PMID- 27249110 TI - Patient-specific instrumentation does not improve radiographic alignment or clinical outcomes after total knee arthroplasty. AB - Background and purpose - Patient-specific instrumentation (PSI) for total knee arthroplasty (TKA) has been introduced to improve alignment and reduce outliers, increase efficiency, and reduce operation time. In order to improve our understanding of the outcomes of patient-specific instrumentation, we conducted a meta-analysis. Patients and methods - We identified randomized and quasi randomized controlled trials (RCTs) comparing patient-specific and conventional instrumentation in TKA. Weighted mean differences and risk ratios were determined for radiographic accuracy, operation time, hospital stay, blood loss, number of surgical trays required, and patient-reported outcome measures. Results - 21 RCTs involving 1,587 TKAs were included. Patient-specific instrumentation resulted in slightly more accurate hip-knee-ankle axis (0.3 degrees ), coronal femoral alignment (0.3 degrees , femoral flexion (0.9 degrees ), tibial slope (0.7 degrees ), and femoral component rotation (0.5 degrees ). The risk ratio of a coronal plane outlier (> 3 degrees deviation of chosen target) for the tibial component was statistically significantly increased in the PSI group (RR =1.64). No significance was found for other radiographic measures. Operation time, blood loss, and transfusion rate were similar. Hospital stay was significantly shortened, by approximately 8 h, and the number of surgical trays used decreased by 4 in the PSI group. Knee Society scores and Oxford knee scores were similar. Interpretation - Patient-specific instrumentation does not result in clinically meaningful improvement in alignment, fewer outliers, or better early patient reported outcome measures. Efficiency is improved by reducing the number of trays used, but PSI does not reduce operation time. PMID- 27249158 TI - Study of spatial and temporal distribution of antimicrobial in water and sediments from caging fish farms by on-line SPE-LC-MS/MS. AB - An on-line solid phase extraction liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method for the determination of 12 antimicrobials in sediment and surface water was developed and validated. Furthermore, the spatial and temporal antimicrobials distributions in the sediment and in the water of four fish farms located in the hydroelectric dam of Ilha Solteira Reservoir in Brazil were investigated over four seasons in three sampling sites: at the fish cages, 100 and 1,000 m downstream far from the cages. The method was performed using an Agilent Zorbax 80 SB-C8 column (9.4 * 15 mm, 5 um) as the loading column, and the Agilent Zorbax Eclipse Plus C18 column (3.0 * 100 mm, 3.5 um) as a separation column within a run time of 13 min. The limits of quantification were less than 9 ng.L(-1) for the antibiotics in water and 16 ug.kg(-1) in sediment; the recovery ranged from 80 to 119%, with a variation coefficient less than 11%, and the repeatability was lower than 15%. Oxytetracycline was found in the water in all sample seasons. However, florfenicol was identified in April and October 2013 and January 2014, and tetracycline was present in July 2013. Regarding the sediment, oxytetracycline and tetracycline were found in all sampling periods, but chlortetracycline was only identified in January 2014. The spatial distribution of antimicrobials showed that the main pollution source came from the fish farms. This study demonstrated that the proposed method is reliable for the monitoring of antimicrobials in water and sediments and it showed contamination in both matrices from Ilha Solteira Reservoir. PMID- 27249159 TI - Affect in the eyes: explicit and implicit evaluations. AB - The present study investigated whether another individual's gaze direction influences an observer's affective responses. In Experiment 1, subjective self ratings and an affective priming paradigm were employed to examine how participants explicitly and implicitly, respectively, evaluated the affective valence of direct gaze, averted gaze, and closed eyes. The explicit self-ratings showed that participants evaluated closed eyes more positively than direct gaze. However, the implicit priming task showed an inverse pattern of results indicating that direct gaze was automatically evaluated more positively than closed eyes were. Experiment 2 confirmed that the opposite patterns of results between the two tasks were not due to differences in presentation times of the gaze stimuli. The results provide evidence for automatic affective reactions to eye gaze and indicate a dissociation between explicit and implicit affective evaluations of eyes and gaze direction. PMID- 27249160 TI - Bipartisan Genetic Research Privacy Protection Act Introduced. PMID- 27249161 TI - Internet- and mobile-based stress management for employees with adherence-focused guidance: efficacy and mechanism of change. AB - OBJECTIVE: This randomized controlled trial (RCT) aimed to evaluate the efficacy of an internet-based stress management intervention (iSMI) among employees compared to a 6-month waitlist control group (WLC) with full access to treatment as-usual. METHOD: A sample of 264 employees with elevated symptoms of perceived stress (Perceived Stress Scale, PSS-10 >=22) was assigned to either the iSMI or WLC group. The iSMI consisted of seven sessions and one booster session including problem-solving and emotion regulation techniques. Participants received guidance from an e-coach that focused on improving the adherence to the intervention. Self report data were assessed at baseline, seven weeks, and six months following randomization. The primary outcome was perceived stress (PSS-10). The secondary outcomes included other relevant mental and work-related health outcomes. RESULTS: The iSMI participants showed a significantly higher reduction in perceived stress from baseline to seven weeks [d=0.79, 95% confidence interval (95% CI) 0.54-1.04] and the 6-month follow up (d=0.85, 95% CI 0.59-1.10) compared to controls. Significant moderate-to-large effect sizes were also found for depression, anxiety, emotional exhaustion, sleeping problems, worrying, quality of life (mental health), psychological detachment and emotion regulation skills. Work engagement, quality of life (physical health), absenteeism and presenteeism were not found to significantly differ between the iSMI and WLC groups. Changes in emotion regulation regarding general distress mediated changes in perceived stress. CONCLUSION: The iSMI investigated in this study was found to be effective in reducing typical symptoms of stress. However, several important work-related health symptoms were not significantly affected by the intervention. Internet based guided self-help interventions could be an acceptable, effective approach to reduce a range of negative consequences associated with work-related stress. Future studies should investigate the comparative (cost-) effectiveness of guided and unguided stress management interventions. PMID- 27249162 TI - Simple animal models for amyotrophic lateral sclerosis drug discovery. AB - INTRODUCTION: Simple animal models have enabled great progress in uncovering the disease mechanisms of amyotrophic lateral sclerosis (ALS) and are helping in the selection of therapeutic compounds through chemical genetic approaches. AREAS COVERED: Within this article, the authors provide a concise overview of simple model organisms, C. elegans, Drosophila and zebrafish, which have been employed to study ALS and discuss their value to ALS drug discovery. In particular, the authors focus on innovative chemical screens that have established simple organisms as important models for ALS drug discovery. EXPERT OPINION: There are several advantages of using simple animal model organisms to accelerate drug discovery for ALS. It is the authors' particular belief that the amenability of simple animal models to various genetic manipulations, the availability of a wide range of transgenic strains for labelling motoneurons and other cell types, combined with live imaging and chemical screens should allow for new detailed studies elucidating early pathological processes in ALS and subsequent drug and target discovery. PMID- 27249164 TI - The Vital Relationship Between Nutrition and Health in Zebrafish. AB - In the relatively short span of four decades, the zebrafish (Danio rerio) has emerged as an increasingly important model organism for biomedicine and other scientific disciplines. As the scale and sophistication of zebrafish research expands, so too does the need to develop standards that promote the production and maintenance of healthy animals for experiments. A major, but long overlooked, contributor to fish health is nutrition. Historically, feeding practices for laboratory zebrafish have been designed to promote growth and reproductive function. However, as the field matures, it is becoming increasingly clear that the nutritional goals for these animals should evolve beyond basic production to the maintenance of clinically healthy research subjects. This review outlines weaknesses and limitations of current approaches and provides a justification for the development of defined standardized diets that will strengthen and facilitate the continued growth of the zebrafish model system. PMID- 27249163 TI - Bispecific antibodies in cancer immunotherapy. AB - Cancer immunotherapy has recently generated much excitement after the continuing success of the immunomodulating anti-CTLA-4 and anti-PD-1 antibodies against various types of cancers. Aside from these immunomodulating antibodies, bispecific antibodies, chimeric antigen receptor T cells, and other technologies are being actively studied. Among the various approaches to cancer immunotherapy, 2 bispecific antibodies are currently approved for patient care. Many more bispecific antibodies are now in various phases of clinical development and will become the next generation of antibody-based therapies. Further understanding of immunology and advances in protein engineering will help to generate a greater variety of bispecific antibodies to fight cancer. Here, we focus on bispecific antibodies that recruit immune cells to engage and kill tumor cells. PMID- 27249165 TI - Electro-deposited poly-luminol molecularly imprinted polymer coating on carboxyl graphene for stir bar sorptive extraction of estrogens in milk. AB - Electrochemical polymerization of luminol molecularly imprinted polymer on carboxyl graphene (MIP/CG) was developed as stir bar sorptive extraction (SBSE) coating for selective pre-concentration and specific recognition of bisphenol A (BPA), hexoestrol and diethylstilbestrol in milk samples. Luminol was employed as monomer and BPA as the template to prepare MIP under 0-0.6V electro polymerization. Carboxyl graphene was modified on pencil lead as the substrate to increase extraction capacity. The preparation and extraction conditions affecting the extraction efficiency were optimized. Under the optimized conditions, a good linearity of three estrogens was obtained in the range of 4-1000ngmL(-1). The average recoveries at the three spiked levels of the three estrogens ranged from 83.4% to 96.3% with the relative standard deviations (RSD)<=7.1%. The limits of detection were in the range of 0.36-1.09ngmL(-1). The developed method with low cost, high selectivity and good reproducibility can be potentially applied for determining trace estrogens in complex food samples. PMID- 27249166 TI - Synergistic Effects of Metals in a Promising Ru(II) -Pt(II) Assembly for a Combined Anticancer Approach: Theoretical Exploration of the Photophysical Properties. AB - Ru(II) -Pt(II) complexes are a class of bioactive molecules of interest as anticancer agents that combine a light-absorbing chromophore with a cisplatin like unit. The results of a DFT and TDDFT investigation of a Ru(II) complex and its conjugate with a cis-PtCl2 moiety reveal that a synergistic effect of the metals makes the assembly a promising multitarget anticancer drug. Inspection of type I and type II photoreactions and spin-orbit coupling computations reveals that the cis-PtCl2 moiety improves the photophysical properties of the Ru(II) chromophore, ensuring efficient singlet oxygen generation and making the assembly suitable for photodynamic therapy. At the same time, the Ru(II) chromophore promotes a new alternative activation mechanism of the Pt(II) ligand via a triplet metal-to-ligand charge transfer ((3) MLCT) state, before reaching the biological target. The importance of the supramolecular architecture is accurately derived, opening interesting new perspectives on the use of bimetallic Ru(II) -Pt(II) assemblies in a combined anticancer approach. PMID- 27249167 TI - Methanol diffusion in zeolite HY: a combined quasielastic neutron scattering and molecular dynamics simulation study. AB - The diffusion of methanol in zeolite HY is studied using tandem quasielastic neutron scattering (QENS) experiments and molecular dynamics (MD) simulations at 300-400 K. The experimental diffusion coefficients were measured in the range 2-5 * 10(-10) m(2) s(-1) and simulated diffusion coefficients calculated in the range of 1.6-3.2 * 10(-9) m(2) s(-1). Activation energies were measured as 8.8 and 6.9 kJ mol(-1) using QENS and MD respectively. Differences may be attributed predominantly to the experimental use of a dealuminated HY sample, containing significant defects such as strongly adsorbing silanol nests, compared to a perfect simulated crystal containing only evenly distributed Bronsted acid sites. Experimental and simulated diffusivities measured in this study are lower than those obtained from those previously calculated in siliceous faujasite, due to methanol H-bonding to Bronsted acid sites as observed in the MD simulations. However, both experimental and simulated diffusivities were significantly higher than those obtained in NaX, due to the higher concentration of extraframework cations present in the previously studied structures. PMID- 27249168 TI - Revised Conceptual Framework of Parent-to-Parent Support for Parents of Children Who Are Deaf or Hard of Hearing: A Modified Delphi Study. AB - BACKGROUND: A scoping review of the literature was conducted, resulting in the development of a conceptual framework of parent-to-parent support for parents with children who are Deaf or hard of hearing. This is the 2nd stage of a dual stage scoping review. PURPOSE: This study sought stakeholder opinion and feedback with an aim to achieve consensus on the constructs, components, and design of the initial conceptual framework. RESEARCH DESIGN: A modified electronic Delphi study was completed with 21 handpicked experts from 7 countries who have experience in provision, research, or experience in the area of parent-to-parent support. Participants completed an online questionnaire using an 11-point Likert scale (strongly disagree to strongly agree) and open-ended questions to answer various questions related to the descriptor terms, definitions, constructs, components, and overall design of the framework. RESULTS: Participant responses led to the revision of the original conceptual framework. CONCLUSION: The findings from this dual-stage scoping review and electronic Delphi study provide a conceptual framework that defines the vital contribution of parents in Early Hearing Detection and Intervention programs that will be a useful addition to these programs. PMID- 27249169 TI - Fabricating Nanometer-Thick Simultaneously Oleophobic/Hydrophilic Polymer Coatings via a Photochemical Approach. AB - The simultaneously oleophobic/hydrophilic coatings are highly desirable in antifogging, oil-water separation, and detergent-free cleaning. However, such coatings require special chemical structure, i.e., perfluorinated backbone and polar end-groups, and are too expensive for real-life application. Here, we have developed an UV-based photochemical approach to make nanometer-thick perfluoropolyethers without polar end-groups, which are not intrinsically simultaneously oleophobic/hydrophilic but cost-effective, become simultaneously oleophobic/hydrophilic. The contact angle, ellipsometry, and X-ray photoelectron spectroscopy (XPS) results indicated that the UV irradiation results in the covalent bonding between the polymer and the substrate, which renders more ordered packing of polymer chains and thus the appropriately small interchain distance. As a result, the small water molecules penetrate the polymer network while large oil molecules do not. As a result, the oil contact angle is larger than the water contact angle and the coating shows the simultaneous oleophobicity/hydrophilicity. Moreover, we also demonstrated that this nanometer thick simultaneously oleophobic/hydrophilic coating has improved long-term antifogging performance and detergent-free cleaning capability and is mechanically robust. The photochemical approach established here potentially can be applied on many other polymers and greatly accelerate the development and application of simultaneously oleophobic/hydrophilic coatings. PMID- 27249170 TI - Effect on Gel Formation Time of Adding Topical Ophthalmic Medications to ReSure Sealant, an In Situ Hydrogel. AB - PURPOSE: The purpose of this study was to describe the gel formation times of ReSure((r)) Sealant, an in situ hydrogel approved to seal cataract surgery incisions, when commercially available topical medications are mixed with the sealant. METHODS: In this experimental laboratory study, the commercial product, ReSure Sealant, was used as per the product insert. Two drops of diluent were mixed with the polymer and time to gel formation was measured. Following this, various commercial antibiotic, nonsteroidal anti-inflammatory drug and steroid drops were used in substitution of one of the drops of the diluent. Combinations of 2 medications were also tested. Each condition was performed in triplicate and the mean gel time was calculated. RESULTS: The addition of bromfenac slightly reduced mean gel time from 19 s (ReSure alone) to 13 s. All other medications, including moxifloxacin, gatifloxacin, ofloxacin, ciprofloxacin, loteprednol etabonate, prednisolone acetate, dexamethasone, ketorolac, and nepafenac, increased mean gel time, ranging from 49 s to >120 s. The addition of bromfenac to moxifloxacin, ofloxacin, or gatifloxacin reduced their mean gel times from >=105 s to 18-29 s. CONCLUSIONS: Certain medications, specifically bromfenac, may not substantially alter time to gel formation of ReSure Sealant when added to the hydrogel. In fact, bromfenac added to moxifloxacin, ofloxacin, or gatifloxacin reduced gel formation time to acceptable levels. All other medications and combinations of medications added to ReSure Sealant produced unacceptably long gel times to be used routinely. Clinical studies may be considered based on these results to assess the safety and efficacy of this strategy. PMID- 27249172 TI - Exploration of Sedentary Behavior in Residential Substance Abuse Populations: Results From an Intervention Study. AB - BACKGROUND: There is a growing body of research linking sedentary behavior with increased risk of chronic disease and all-cause mortality. It is increasingly recommended that service providers address the multiple behavioral risk factors associated with these chronic diseases as part of routine substance abuse treatment. OBJECTIVES: The study objective was to investigate rates of physical activity and sedentary behavior in a residential substance abuse population. In addition, efficacy of a sedentary behavior intervention, "Sit Switch," was examined for feasibility in this context. METHODS: Participants (n = 54) were residents of The Salvation Army Recovery Service Centres located in Canberra and on the Gold Coast, Australia. Actigraph GT3X+ accelerometers were used to measure rates and patterns of sedentariness and physical activity. A nonrandomized controlled study of a single-session group intervention aimed at decreasing prolonged sitting ("Sit Switch") was conducted. Education, motivational interviewing, and goal setting components underpinned the "Sit Switch" intervention. RESULTS: Individuals were highly sedentary, spending 73% of daily activity at sedentary intensity engaged in inadequate levels of moderate physical activity (6.6%/day). The single session educational program did not lead to any significant changes in sedentary behavior. Conclusion/Importance: High levels of sedentariness and low levels of physical activity engagement are evident in residents in substance abuse treatment programs. It is strongly recommended that sedentariness, a modifiable risk behavior with independent consequences for cardiovascular disease and cancer, be addressed within residential programs. PMID- 27249173 TI - Synthesis, Structure, and Photophysical Properties of Mo2(NN)4 and Mo2(NN)2(T(i)PB)2, Where NN = N,N'-Diphenylphenylpropiolamidinate and T(i)PB = 2,4,6-Triisopropylbenzoate. AB - Two dimolybdenum compounds featuring amidinate ligands with a C=C bond, Mo2(NN)4 (I), where NN = N,N'-diphenylphenylpropiolamidinate, and trans-Mo2(NN)2(T(i)PB)2 (II), where T(i)PB = 2,4,6-triisopropylbenzoate, have been prepared and structurally characterized by single-crystal X-ray crystallography. Together with Mo2(DAniF)4 (III), where DAniF = N,N'-bis(p-anisyl)formamidinate, all three compounds have been studied with steady-state UV-vis, IR, and time-resolved spectroscopy methods. I and II display intense metal to ligand charge transfer (MLCT). Singlet state (S1) lifetimes of I-III are determined to be 0.7, 19.1, and 2.0 ps, respectively. All three compounds have long-lived triplet state (T1) lifetimes around 100 MUs. In femtosecond time-resolved infrared (fs-TRIR) experiments, one nu(C=C) band is observed at the S1 state for I but two for II, which indicate different patterns of charge distribution. The electron would have to be localized on one NN ligand in I and partially delocalized over two NN ligands in II to account for the observations. The result is a standard showcase of excited-state mixed valence in coordination compounds. PMID- 27249171 TI - The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling. AB - Tumour necrosis factor receptor-associated factor 6 (TRAF6) is a ubiquitin E3 ligase that regulates important biological processes. However, the role of TRAF6 in cardiac hypertrophy remains unknown. Here, we show that TRAF6 levels are increased in human and murine hypertrophied hearts, which is regulated by reactive oxygen species (ROS) production. Cardiac-specific Traf6 overexpression exacerbates cardiac hypertrophy in response to pressure overload or angiotensin II (Ang II) challenge, whereas Traf6 deficiency causes an alleviated hypertrophic phenotype in mice. Mechanistically, we show that ROS, generated during hypertrophic progression, triggers TRAF6 auto-ubiquitination that facilitates recruitment of TAB2 and its binding to transforming growth factor beta-activated kinase 1 (TAK1), which, in turn, enables the direct TRAF6-TAK1 interaction and promotes TAK1 ubiquitination. The binding of TRAF6 to TAK1 and the induction of TAK1 ubiquitination and activation are indispensable for TRAF6-regulated cardiac remodelling. Taken together, we define TRAF6 as an essential molecular switch leading to cardiac hypertrophy in a TAK1-dependent manner. PMID- 27249174 TI - Maximum-Intensity-Projection and Computer-Aided-Detection Algorithms as Stand Alone Reader Devices in Lung Cancer Screening Using Different Dose Levels and Reconstruction Kernels. AB - OBJECTIVE: The objective of our study was to evaluate lung nodule detection rates on standard and microdose chest CT with two different computer-aided detection systems (SyngoCT-CAD, VA 20, Siemens Healthcare [CAD1]; Lung CAD, IntelliSpace Portal DX Server, Philips Healthcare [CAD2]) as well as maximum-intensity projection (MIP) images. We also assessed the impact of different reconstruction kernels. MATERIALS AND METHODS: Standard and microdose CT using three reconstruction kernels (i30, i50, i70) was performed with an anthropomorphic chest phantom. We placed 133 ground-glass and 133 solid nodules (diameters of 5 mm, 8 mm, 10 mm, and 12 mm) in 55 phantoms. Four blinded readers evaluated the MIP images; one recorded the results of CAD1 and CAD2. Sensitivities for CAD and MIP nodule detection on standard dose and microdose CT were calculated for each reconstruction kernel. RESULTS: Dose for microdose CT was significantly less than that for standard-dose CT (0.1323 mSv vs 1.65 mSv; p < 0.0001). CAD1 delivered superior results compared with CAD2 for standard-dose and microdose CT (p < 0.0001). At microdose level, the best stand-alone sensitivity (97.6%) was comparable with CAD1 sensitivity (96.0%; p = 0.36; both with i30 reconstruction kernel). Pooled sensitivities for all nodules, doses, and reconstruction kernels on CAD1 ranged from 88.9% to 97.3% versus 49.6% to 73.9% for CAD2. The best sensitivity was achieved with standard-dose CT, i50 kernel, and CAD1 (97.3%) versus 96% with microdose CT, i30 or i50 kernel, and CAD1. MIP images and CAD1 had similar performance at both dose levels (p = 0.1313 and p = 0.48). CONCLUSION: Submillisievert CT is feasible for detecting solid and ground-glass nodules that require soft-tissue kernels for MIP and CAD systems to achieve acceptable sensitivities. MIP reconstructions remain a valuable adjunct to the interpretation of chest CT for increasing sensitivity and have the advantage of significantly lower false-positive rates. PMID- 27249175 TI - Evolving landscape of tumor molecular profiling for personalized cancer therapy: a comprehensive review. AB - INTRODUCTION: Tumour molecular profiling has been at the crossroads of large scale integrative genomic studies and major clinical trials over the past 5 years and has provided roadmaps for better disease stratification and therapeutic management. AREAS COVERED: We review the landscape of precision oncology trials in Asia, Europe and the United States, and emerging insights gained from recently reported studies such as the SHIVA and CUSTOM trials. Changes in the molecular portraits of human cancers and the immune contexture of the tumor microenvironment during treatment may predict the course of tumor progression, including the development of treatment resistance. 'Liquid biopsy' approaches that harness circulating tumor cells, cell-free DNA and exosomes may provide a non-invasive means of monitoring the parent tumor in real-time. Several molecular signatures are being evaluated as biomarkers for emerging immunologic approaches, such as the mismatch-repair deficiency status and nonsynonymous mutation burden in anti-PD-1 immune checkpoint blockade. Finally, we review the current actionability and future clinical impact of multigene panel and next-generation sequencing (NGS)-based profiling. EXPERT OPINION: In the future, molecular profiling may help to fulfill unmet needs for predictive biomarkers in novel immunotherapeutic approaches, while ongoing precision trials are laying the foundations for clinical uptake of NGS testing. PMID- 27249176 TI - Molecular architecture of the recombinant human MCM2-7 helicase in complex with nucleotides and DNA. AB - DNA replication is a key biological process that involves different protein complexes whose assembly is rigorously regulated in a successive order. One of these complexes is a replicative hexameric helicase, the MCM complex, which is essential for the initiation and elongation phases of replication. After the assembly of a double heterohexameric MCM2-7 complex at replication origins in G1, the 2 heterohexamers separate from each other and associate with Cdc45 and GINS proteins in a CMG complex that is capable of unwinding dsDNA during S phase. Here, we have reconstituted and characterized the purified human MCM2-7 (hMCM2-7) hexameric complex by co-expression of its 6 different subunits in insect cells. The conformational variability of the complex has been analyzed by single particle electron microscopy in the presence of different nucleotide analogs and DNA. The interaction with nucleotide stabilizes the complex while DNA introduces conformational changes in the hexamer inducing a cylindrical shape. Our studies suggest that the assembly of GINS and Cdc45 to the hMCM2-7 hexamer would favor conformational changes on the hexamer bound to ssDNA shifting the cylindrical shape of the complex into a right-handed spiral conformation as observed in the CMG complex bound to DNA. PMID- 27249178 TI - Nature of Hydrogen Bonds and S...S Interactions in the l-Cystine Crystal. AB - The intermolecular interactions that govern the stability of the l-cystine crystal were studied. This task is accomplished by using density-functional theory (DFT) with the generalized-gradient approximation (GGA) and including many body dispersion (MBD) interactions. The strengths of the different interactions within the molecular crystal were obtained by a decomposition of the total interaction energy in two-, three-, and four-body contributions. It was determined that most of the hydrogen bonds formed within the crystal are strong (13, 15, and 19 kcal/mol) and the van der Waals nature of the S...S interaction is fully confirmed. Also, the presence of strong repulsive three-body contributions is determined. The results obtained support the idea of designing crystal growth inhibitors for this system in such a way that, when inserted in the crystal, they maintain the disulfide bridge environment but its capacity of generate hydrogen-bond networks is removed. PMID- 27249179 TI - Cerebral Effects of Targeted Temperature Management Methods Assessed by Diffusion Weighted Magnetic Resonance Imaging. AB - The aim of this randomized porcine study was to compare surface targeted temperature management (TTM) to endovascular TTM evaluated by cerebral diffusion weighted magnetic resonance imaging (MRI): apparent diffusion coefficient (ADC), and by intracerebral/intramuscular microdialysis. It is well known that alteration in the temperature affects ADC, but the relationship between cerebral ADC values and the cooling method per se has not been established. Eighteen anesthetized 60-kg female swine were hemodynamically and intracerebrally monitored and subsequently subjected to a baseline MRI. The animals were then randomized into three groups: (1) surface cooling (n = 6) at 33.5 degrees C using EMCOOLSpad(r), (2) endovascular cooling (n = 6) at 33.5 degrees C using an Icy(r) cooling catheter with the CoolGard 3000(r), or (3) control (n = 6) at 38.5 degrees C using a Bair HuggerTM. The swine were treated with TTM for 6 hours followed by a second MRI examination, including ADC. Blood and microdialysate were sampled regularly throughout the experiment, and glucose, lactate, pyruvate, glycerol, and the lactate/pyruvate ratio did not differ among groups, neither intracerebrally nor intramuscularly. Surface cooling yielded a significantly lower median ADC than endovascular cooling: 714 (634; 804) * 10-6 mm2/s versus 866 (828; 927) * 10-6 mm2/s, (p < 0.05). The surface cooling ADC was lowered to a range usually attributed to cytotoxic edema and these low values could not be explained solely by the temperature effect per se. To what extent the ADC is fully reversible at rewarming is unknown and the clinical implications should be further investigated in clinical studies. PMID- 27249180 TI - Interventions to Reduce Compulsory Psychiatric Admissions: A Systematic Review and Meta-analysis. AB - IMPORTANCE: Compulsory admissions, defined as admissions against the will of the patient (according to local judicial procedures), have a strong effect on psychiatric patients. In several Western countries, the rate of such admissions is tending to rise. Its reduction is urgently needed. OBJECTIVE: To establish which interventions effectively reduce compulsory admissions in adult psychiatric patients in outpatient settings. DATA SOURCES: A systematic computerized literature search was performed using EMBASE, MEDLINE, Web of Science, PsycINFO, CINAHL, PubMed (not yet indexed for MEDLINE), Cochrane Central, and Google Scholar. Every database was searched from its inception until April 30, 2015. STUDY SELECTION: Randomized clinical trials (RCTs) that studied any kind of intervention designed to reduce compulsory admission rates in adult psychiatric patients (age range, 18-65 years) in outpatient settings were eligible. Eligibility was independently assessed by 2 of us. DATA EXTRACTION AND SYNTHESIS: Two of us independently extracted relevant data. The Cochrane Collaboration's tool was used for assessing risk of bias. Overall risk reduction (random-effects estimate) was calculated in the following 4 subgroups of interventions: advance statements, community treatment orders, compliance enhancement, and integrated treatment. MAIN OUTCOMES AND MEASURES: Relative risk (RR) was calculated on the basis of the number of patients who had been compulsorily admitted. RESULTS: Our meta-analyses included 13 RCTs comprising 2970 psychiatric patients. The meta analysis of the RCTs on advance statements showed a significant 23% (RR, 0.77; 95% CI, 0.60-0.98; I2 = 2.2%) (n = 1102) risk reduction in compulsory admissions. In contrast, the RCTs on community treatment orders (RR, 0.95; 95% CI, 0.81-1.10; I2 = 0.0%) (n = 742), compliance enhancement (RR, 0.52; 95% CI, 0.11-2.37; I2 = 55.7%) (n = 250), and integrated treatment (RR, 0.71; 95% CI, 0.49-1.02; I2 = 49.0%) (n = 876) showed no significant risk reduction in compulsory admissions. CONCLUSIONS AND RELEVANCE: The meta-analysis of the RCTs on advance statements showed a statistically significant and clinically relevant 23% reduction in compulsory admissions in adult psychiatric patients, whereas the meta-analyses of the RCTs on community treatment orders, compliance enhancement, and integrated treatment showed no evidence of such a reduction. To date, only 13 RCTs have used compulsory admissions as their primary or secondary outcome measure. This demonstrates the need for more research in this field. PMID- 27249181 TI - Efficient Transfection by Using PDMAEMA-Modified SiNWAs as a Platform for Ca(2+) Dependent Gene Delivery. AB - The major bottleneck for gene delivery lies in the lack of safe and efficient gene vectors and delivery systems. In order to develop a much safer and efficient transfection system, a novel strategy of combining traditional Ca(2+)-dependent transfection with cationic polymer poly(N,N-dimethylamino)ethyl methacrylate (PDMAEMA) modified silicon nanowire arrays (SiNWAs) was proposed in this work. Detailed studies were carried out on the effects of the PDMAEMA polymerization time, the Ca(2+) concentration, and the incubation time of Ca(2+)@DNA complex with PDMAEMA-modified SiNWAs (SN-PDM) on the gene transfection in the cells. The results demonstrated that the transfection efficiency of SN-PDM assisted traditional Ca(2+)-dependent transfection was significantly enhanced compared to those without any surface assistance, and SN-PDM with polymerization time 24 h exhibited the highest efficiency. Moreover, the optimal transfection efficiency was found at the system of a complex containing Ca(2+) (100 mM) and plasmid DNA (pDNA) incubated on SN-PDM for 20 min. Compared with unmodified SiNWAs, SN-PDM has little cytotoxicity and can improve cell attachment. All of these results demonstrated that SN-PDM could significantly enhance Ca(2+)-dependent transfection; this process depends on the amino groups' density of PDMAEMA on the surface, the Ca(2+) concentration, and the available Ca(2+)@DNA complex. Our study provides a potential novel and excellent means of gene delivery for therapeutic applications. PMID- 27249182 TI - Larvicidal and Adulticidal Activity of Chroman and Chromene Analogues against Susceptible and Permethrin-Resistant Mosquito Strains. AB - Mosquitoes play a major role as vectors that transmit parasitic and viral diseases worldwide, especially in tropical and subtropical countries. Mosquito borne diseases not only affect humans but they also affect livestock in many parts of the world. They carry diseases that are lethal to dogs and horses. Dog heartworm disease (Dirofilaria immitis) is a parasitic disease spread through mosquitoes. This disease is not limited to dogs, but it can affect other animals and humans as well. Eastern equine encephalitis (EEE) and West Nile virus (WNV) are also mosquito borne diseases that affect the central nervous system of horses and cause severe complications and death. Emergence of resistance among mosquitoes to current pesticides has increased the importance of the search for alternate compounds that are effective and environmentally benign with diverse modes of actions than those that are commercially available. Aedes aegypti mosquitoes are the primary vector for transmission of Zika viral fever, yellow fever, dengue fever, and chikungunya. Mosquito control is currently the best strategy to prevent mosquito borne diseases. There are numerous approaches for control of potentially dangerous mosquito populations. These approaches include the use of adulticides (insecticides), larvicides, and, to a limited extent, the use of repellents. Our previous studies have shown the mosquito repellent activity of chromenes. In the present study, we demonstrate larvicidal and adulticidal activity of chroman and chromene analogues against a permethrin susceptible laboratory strain as well as activity against a permethrin-resistant strain of Aedes aegypti. PMID- 27249183 TI - Biobanking with Big Data: A Need for Developing "Big Data Metrics". AB - The term "big data" has often been used as an all-encompassing phrase for research that involves the use of large-scale data sets. However, the use of the term does little to signify the underlying complexity of definitions, of data sets, and of the requirements that need to be taken into consideration for sustainable research and the estimation of downstream impact. In particular, "big data" is frequently connected with biobanks and biobank networks as the institutions involved in tissue preservation are increasingly and perhaps unavoidably linked to the de facto preservation of information. PMID- 27249184 TI - Diffusion-weighted MRI in Crohn's disease: Current status and recommendations. AB - Over the past years, technological improvements and refinements in magnetic resonance imaging (MRI) hardware have made high-quality diffusion-weighted imaging (DWI) routinely possible for the bowel. DWI is promising for the detection and characterization of lesions in Crohn's disease (CD) and has been advocated as an alternative to intravenous gadolinium-based contrast agents. Furthermore, quantification using the apparent diffusion coefficient may have value as a biomarker of CD activity and has shown promise. In this article we critically review the literature pertaining to the value of DWI in CD for detection, characterization, and quantification of disease activity and complications. Although the body of supportive evidence is growing, it is clear that well-designed, multicenter studies are required before the role of DWI in clinical practice can be fully established. J. Magn. Reson. Imaging 2016;44:1381 1396. PMID- 27249185 TI - Sequential transurethral enucleation of the prostate and laparoscopic bladder diverticulectomy. AB - Transurethral endoscopic technique and standard laparoscopic technique are surgical options for the management of benign prostatic hyperplasia (BPH) associated with urinary bladder diverticuli (UBD). In this article, we report laparoscopic diverticulectomy (LD) and transurethral plasmakinetic enucleation of the prostate (TUEP) in the same patient sequentially. To the best of our knowledge, this is the first case report of LD combined with TUEP. An 82-year-old patient with benign prostatic hyperplasia and two secondary large bladder diverticuli underwent sequential TUEP and LD. After completion of the TUEP procedure, the detached adenoma was pushed into the bladder as a whole. Then laparoscopic transperitoneal extravesical diverticulectomy assisted by cystoscopic transillumination was performed immediately, and the enucleated prostate was removed via the neck of the diverticulum. The enucleation time and diverticulectomy time was 18 minutes and 108 minutes, respectively. The catheter was removed on the tenth postoperative day. Transurethral endoscopic surgery combined with LD is a good choice in treating BPH and UBD in one session. But the combined procedure is time-consuming, especially for fragmentation of the prostate. TUEP can greatly reduce the operative time of the combined procedure. PMID- 27249186 TI - Structural Transitions in Cholesteric Liquid Crystal Droplets. AB - Confinement of cholesteric liquid crystals (ChLC) into droplets leads to a delicate interplay between elasticity, chirality, and surface energy. In this work, we rely on a combination of theory and experiments to understand the rich morphological behavior that arises from that balance. More specifically, a systematic study of micrometer-sized ChLC droplets is presented as a function of chirality and surface energy (or anchoring). With increasing chirality, a continuous transition is observed from a twisted bipolar structure to a radial spherical structure, all within a narrow range of chirality. During such a transition, a bent structure is predicted by simulations and confirmed by experimental observations. Simulations are also able to capture the dynamics of the quenching process observed in experiments. Consistent with published work, it is found that nanoparticles are attracted to defect regions on the surface of the droplets. For weak anchoring conditions at the nanoparticle surface, ChLC droplets adopt a morphology similar to that of the equilibrium helical phase observed for ChLCs in the bulk. As the anchoring strength increases, a planar bipolar structure arises, followed by a morphological transition to a bent structure. The influence of chirality and surface interactions are discussed in the context of the potential use of ChLC droplets as stimuli-responsive materials for reporting molecular adsorbates. PMID- 27249187 TI - Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement. AB - Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD. PMID- 27249188 TI - Gene-Specific Assessment of Guanine Oxidation as an Epigenetic Modulator for Cardiac Specification of Mouse Embryonic Stem Cells. AB - Epigenetics have essential roles in development and human diseases. Compared to the complex histone modifications, epigenetic changes on mammalian DNA are as simple as methylation on cytosine. Guanine, however, can be oxidized as an epigenetic change which can undergo base-pair transversion, causing a genetic difference. Accumulating evidence indicates that reactive oxygen species (ROS) are important signaling molecules for embryonic stem cell (ESC) differentiation, possibly through transient changes on genomic DNA such as 7,8-dihydro-8 oxoguanine (8-oxoG). Technical limitations on detecting such DNA modifications, however, restrict the investigation of the role of 8-oxoG in ESC differentiation. Here, we developed a Hoogsteen base pairing-mediated PCR-sequencing assay to detect 8-oxoG lesions that can subsequently cause G to T transversions during PCR. We then used this assay to assess the epigenetic and transient 8-oxoG formation in the Tbx5 gene of R1 mouse ESCs subjected to oxidative stress by removing 2-mercaptoethanol (2ME) from the culture media. To our surprise, significantly higher numbers of 8-oxoG-mediated G?C to C?G transversion, not G?C to T?A, were detected at 7th and 9th base position from the transcription start site of exon 1 of Tbx5 in ESCs in the (-)2ME than (+)2ME group (p < 0.05). This was consistent with the decrease in the amount of amplifiable of DNA harboring the 8-oxoG lesions at the Tbx5 promoter region in the oxidative stressed ESCs. The ESCs responded to oxidative stress, possibly through the epigenetic effects of guanine oxidation with decreased proliferation (p < 0.05) and increased formation of beating embryoid bodies (EBs; p < 0.001). Additionally, the epigenetic changes of guanine induced up-regulation of Ogg1 and PolB, two base excision repairing genes for 8-oxoG, in ESCs treated with (-)2ME (p < 0.01). Together, we developed a gene-specific and direct quantification assay for guanine oxidation. Using oxidative stressed mouse ESCs, we validated this assay and assessed the epigenetic effects of 8-oxoG by studying expression of DNA repair genes, ESC proliferation, and EB formation. PMID- 27249189 TI - A symbiotic SNARE protein generated by alternative termination of transcription. AB - Many microbes interact with their hosts across a membrane interface, which is often distinct from existing membranes. Understanding how this interface acquires its identity has significant implications. In the symbiosis between legumes and rhizobia, the symbiosome encases the intracellular bacteria and receives host secretory proteins important for bacterial development. We show that the Medicago truncatula SYNTAXIN 132 (SYP132) gene undergoes alternative cleavage and polyadenylation during transcription, giving rise to two target-membrane soluble NSF attachment protein receptor (t-SNARE) isoforms. One of these isoforms, SYP132A, is induced during the symbiosis, is able to localize to the peribacteroid membrane, and is required for the maturation of symbiosomes into functional forms. The second isoform, SYP132C, has important functions unrelated to symbiosis. The SYP132A sequence is broadly found in flowering plants that form arbuscular mycorrhizal symbiosis, an ancestral mutualism between soil fungi and most land plants. SYP132A silencing severely inhibited arbuscule colonization, indicating that SYP132A is an ancient factor specifying plant-microbe interfaces. PMID- 27249191 TI - Agriculture: Disaster reduction. PMID- 27249190 TI - Genes conserved for arbuscular mycorrhizal symbiosis identified through phylogenomics. AB - Arbuscular mycorrhizal symbiosis (AMS), a widespread mutualistic association of land plants and fungi(1), is predicted to have arisen once, early in the evolution of land plants(2-4). Consistent with this notion, several genes required for AMS have been conserved throughout evolution(5) and their symbiotic functions preserved, at least between monocot and dicot plants(6,7). Despite its significance, knowledge of the plants' genetic programme for AMS is limited. To date, most genes required for AMS have been found through commonalities with the evolutionarily younger nitrogen-fixing Rhizobium legume symbiosis (RLS)(8) or by reverse genetic analyses of differentially expressed candidate genes(9). Large sequence-indexed insertion mutant collections and recent genome editing technologies have vastly increased the power of reverse genetics but selection of candidate genes, from the thousands of genes that change expression during AMS, remains an arbitrary process. Here, we describe a phylogenomics approach to identify genes whose evolutionary history predicts conservation for AMS and we demonstrate the accuracy of the predictions through reverse genetics analysis. Phylogenomics analysis of 50 plant genomes resulted in 138 genes from Medicago truncatula predicted to function in AMS. This includes 15 genes with known roles in AMS. Additionally, we demonstrate that mutants in six previously uncharacterized AMS-conserved genes are all impaired in AMS. Our results demonstrate that phylogenomics is an effective strategy to identify a set of evolutionarily conserved genes required for AMS. PMID- 27249192 TI - In vivo stoichiometry of photorespiratory metabolism. AB - Photorespiration is a major light-dependent metabolic pathway that consumes oxygen and produces carbon dioxide. In the metabolic step responsible for carbon dioxide production, two molecules of glycine (equivalent to two molecules of O2) are converted into one molecule of serine and one molecule of CO2. Here, we use quantitative isotopic techniques to determine the stoichiometry of this reaction in sunflower leaves, and thereby the O2/CO2 stoichiometry of photorespiration. We find that the effective O2/CO2 stoichiometric coefficient at the leaf level is very close to 2 under normal photorespiratory conditions, in line with expectations, but increases slightly at high rates of photorespiration. The net metabolic impact of this imbalance is likely to be modest. PMID- 27249193 TI - Organic agriculture in the twenty-first century. AB - Organic agriculture has a history of being contentious and is considered by some as an inefficient approach to food production. Yet organic foods and beverages are a rapidly growing market segment in the global food industry. Here, we examine the performance of organic farming in light of four key sustainability metrics: productivity, environmental impact, economic viability and social wellbeing. Organic farming systems produce lower yields compared with conventional agriculture. However, they are more profitable and environmentally friendly, and deliver equally or more nutritious foods that contain less (or no) pesticide residues, compared with conventional farming. Moreover, initial evidence indicates that organic agricultural systems deliver greater ecosystem services and social benefits. Although organic agriculture has an untapped role to play when it comes to the establishment of sustainable farming systems, no single approach will safely feed the planet. Rather, a blend of organic and other innovative farming systems is needed. Significant barriers exist to adopting these systems, however, and a diversity of policy instruments will be required to facilitate their development and implementation. PMID- 27249194 TI - Evolutionary patterns of genic DNA methylation vary across land plants. AB - Little is known about patterns of genic DNA methylation across the plant kingdom or about the evolutionary processes that shape them. To characterize gene-body methylation (gbM) within exons, we have gathered single-base resolution methylome data that span the phylogenetic breadth of land plants. We find that a basal land plant, Marchantia polymorpha, lacks any evident signal of gbM within exons, but conifers have high levels of both CG and CHG (where H is A, C or T) methylation in expressed genes. To begin to understand the evolutionary forces that shape gbM, we first tested for correlations in methylation levels across orthologues(1,2). Genic CG methylation levels, but not CHG or CHH levels, are correlated across orthologues for species as distantly related as ferns and angiosperms. Hence, relative levels of CG methylation are a consistent property across genes, even for species that diverged ~400 million years ago(3,4). In contrast, genic CHG methylation correlates with genome size, suggesting that the host epigenetic response to transposable elements also affects genes. Altogether, our data indicate that the evolutionary forces acting on DNA methylation vary substantially across species, genes and methylation contexts. PMID- 27249195 TI - Epichloe grass endophytes in sustainable agriculture. AB - There is an urgent need to create new solutions for sustainable agricultural practices that circumvent the heavy use of fertilizers and pesticides and increase the resilience of agricultural systems to environmental change. Beneficial microbial symbionts of plants are expected to play an important role in integrated pest management schemes over the coming decades. Epichloe endophytes, symbiotic fungi of many grass species, can protect plants against several stressors, and could therefore help to increase the productivity of forage grasses and the hardiness of turf grasses while reducing the use of synthetic pesticides. Indeed, Epichloe endophytes have successfully been developed and commercialized for agricultural use in the USA, Australia and New Zealand. Many of the host grass species originate from Europe, which is a biodiversity hotspot for both grasses and endophytes. However, intentional use of endophyte-enhanced grasses in Europe is virtually non-existent. We suggest that the diversity of European Epichloe endophytes and their host grasses should be exploited for the development of sustainable agricultural, horticultural and landscaping practices, and potentially for bioremediation and bioenergy purposes, and for environmental improvement. PMID- 27249197 TI - Seedling signalling: Ubiquitin ligases acting in tandem. PMID- 27249196 TI - PsbS interactions involved in the activation of energy dissipation in Arabidopsis. AB - The non-photochemical quenching of light energy as heat (NPQ) is an important photoprotective mechanism that is activated in plants when light absorption exceeds the capacity of light utilization in photosynthesis. The PsbS protein plays a central role in this process and is supposed to activate NPQ through specific, light-regulated interactions with photosystem (PS) II antenna proteins. However, NPQ-specific interaction partners of PsbS in the thylakoid membrane are still unknown. Here, we have determined the localization and protein interactions of PsbS in thylakoid membranes in the NPQ-inactive (dark) and NPQ-active (light) states. Our results corroborate a localization of PsbS in PSII supercomplexes and support the model that the light activation of NPQ is based on the monomerization of dimeric PsbS and a light-induced enhanced interaction of PsbS with Lhcb1, the major component of trimeric light-harvesting complexes in PSII. PMID- 27249198 TI - Plant genic methylation: Conserved for 400 million years. PMID- 27249199 TI - Moss development: Starting BELL for embryos. PMID- 27249200 TI - Pathogenomics: Hybrid vs hybrid. PMID- 27249201 TI - Grassland ecology: Nitrogen retention. PMID- 27249202 TI - Epidermal structures: Sculpting with RSL1. PMID- 27249203 TI - Gibberellin signalling: Nectar control. PMID- 27249204 TI - Firm foundations for research. PMID- 27249205 TI - A Pharmacokinetic Study Comparing Eslicarbazepine Acetate Administered Orally as a Crushed or Intact Tablet in Healthy Volunteers. AB - The relative bioequivalence of crushed versus intact eslicarbazepine acetate (ESL) tablets (800 mg) administered orally in healthy adults was evaluated in an open-label, randomized, 2-period crossover study with a 5-day washout between treatments. Sample blood levels of eslicarbazepine and (R)-licarbazepine were determined; pharmacokinetic parameters were derived for eslicarbazepine. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean treatment ratios of eslicarbazepine AUC(0-infinity) and Cmax were within the prespecified 80%-125% range. Twenty-seven subjects in the intent-to treat population (n = 28) completed both treatment periods. Eslicarbazepine exposure measures were similar for crushed versus intact ESL tablets: average Cmax , 11 700 versus 11 500 ng/mL; AUC(0-infinity) , 225 000 versus 234 000 ng.h/mL; AUC(0-last) , 222 000 versus 231 000 ng.h/mL, respectively. Geometric least squares mean ratios (90%CIs) comparing eslicarbazepine exposure measures were within the 80%-125% range (Cmax , 102.63% [97.07%-108.51%]; AUC(0-infinity) , 96.72% [94.36%-99.13%]; AUC0-last , 96.69% [94.24%-99.21%]). In conclusion, ESL administered orally as a crushed tablet sprinkled on applesauce, or intact were bioequivalent in healthy subjects. Eslicarbazepine bioavailability was not significantly altered by crushing, indicating that ESL tablets can be administered intact or crushed. PMID- 27249206 TI - Resistance of Wheat Accessions to the English Grain Aphid Sitobion avenae. AB - The English grain aphid, Sitobion avenae, is a major pest species of wheat crops; however, certain varieties may have stronger resistance to infestation than others. Here, we investigated 3 classical resistance mechanisms (antixenosis, antibiosis, and tolerance) by 14 wheat varieties/lines to S. avenae under laboratory and field conditions. Under laboratory conditions, alatae given the choice between 2 wheat varieties, strongly discriminated against certain varieties. Specifically, the 'Amigo' variety had the lowest palatability to S. avenae alatae of all varieties. 'Tm' (Triticum monococcum), 'Astron,' 'Xanthus,' 'Ww2730,' and 'Batis' varieties also had lower palatability than other varieties. Thus, these accessions may use antibiosis as the resistant mechanism. In contrast, under field conditions, there were no significant differences in the number of alatae detected on the 14 wheat varieties. One synthetic line (98-10 30, a cross between of Triticum aestivum (var. Chris) and Triticum turgidum (var. durum) hybridization) had low aphid numbers but high yield loss, indicating that it has high antibiosis, but poor tolerance. In comparison, 'Amigo,' 'Xiaoyan22,' and some '186Tm' samples had high aphid numbers but low yield loss rates, indicating they have low antibiosis, but good tolerance. Aphid population size and wheat yield loss rates greatly varied in different fields and years for '98 10-35,' 'Xiaoyan22,' 'Tp,' 'Tam200,' 'PI high,' and other '186Tm' samples, which were hybrid offspring of T. aestivum and wheat related species. Thus, these germplasm should be considered for use in future studies. Overall, S. avenae is best adapted to 'Xinong1376,' because it was the most palatable variety, with the greatest yield loss rates of all 14 wheat varieties. However, individual varieties/lines influenced aphid populations differently in different years. Therefore, we strongly recommend a combination of laboratory and long-term field experiments in targeted planting regions to identify varieties/lines that consistently show high resistance to S. avenae infestation. PMID- 27249207 TI - Knockdown of triglyceride synthesis does not enhance palmitate lipotoxicity or prevent oleate-mediated rescue in rat hepatocytes. AB - Experiments in a variety of cell types, including hepatocytes, consistently demonstrate the acutely lipotoxic effects of saturated fatty acids, such as palmitate (PA), but not unsaturated fatty acids, such as oleate (OA). PA+OA co treatment fully prevents PA lipotoxicity through mechanisms that are not well defined but which have been previously attributed to more efficient esterification and sequestration of PA into triglycerides (TGs) when OA is abundant. However, this hypothesis has never been directly tested by experimentally modulating the relative partitioning of PA/OA between TGs and other lipid fates in hepatocytes. In this study, we found that addition of OA to PA-treated hepatocytes enhanced TG synthesis, reduced total PA uptake and PA lipid incorporation, decreased phospholipid saturation and rescued PA-induced ER stress and lipoapoptosis. Knockdown of diacylglycerol acyltransferase (DGAT), the rate-limiting step in TG synthesis, significantly reduced TG accumulation without impairing OA-mediated rescue of PA lipotoxicity. In both wild-type and DGAT knockdown hepatocytes, OA co-treatment significantly reduced PA lipid incorporation and overall phospholipid saturation compared to PA-treated hepatocytes. These data indicate that OA's protective effects do not require increased conversion of PA into inert TGs, but instead may be due to OA's ability to compete against PA for cellular uptake and/or esterification and, thereby, normalize the composition of cellular lipids in the presence of a toxic PA load. PMID- 27249208 TI - Kinetic Resolution of Benzylamines via Palladium(II)-Catalyzed C-H Cross Coupling. AB - A Pd(II)-catalyzed enantioselective C-H cross-coupling of benzylamines via kinetic resolution has been achieved using chiral mono-N-protected alpha-amino-O methylhydroxamic acid (MPAHA) ligands. Both chiral benzylamines and ortho arylated benzylamines are obtained in high enantiomeric purity. The use of a readily removable nosyl (Ns) protected amino group as the directing group is a crucial practical advantage. Moreover, the ortho-arylated benzylamine products could be further transformed into chiral 6-substituted 5,6-dihydrophenanthridines as important structural motifs in natural products and bioactive molecules. PMID- 27249215 TI - Bonding Strength of Ceromer with Direct Laser Sintered, Ni-Cr-Based, and ZrO2 Metal Infrastructures After Er:YAG, Nd:YAG, and Ho:YAG Laser Surface Treatments-A Comparative In Vitro Study. AB - OBJECTIVE: Laser modalities instead of conventional surface treatment techniques have been suggested to obtain an adequate micromechanical bonding between dental super- and infrastructures. The present study was undertaken to assess the effect of surface treatment with Ho:YAG, Er:YAG, and Nd:YAG laser modalities on the shear bond strength (SBS) of ceromer to different types of metal infrastructures in in vitro settings. METHODS: The study specimens consisted of 40 direct laser sintered (DLS), 40 Ni-Cr-based, and 40 zirconium oxide (ZrO2) infrastructures. In each infrastructure group, the specimens were divided randomly into five treatment modalities (n = 8): no treatment (controls), sandblasting, Er:YAG, Nd:YAG, and Ho:YAG lasers. The DLS, Ni-Cr-based, and ZrO2 infrastructures were prepared in the final dimensions of 7 mm in diameter and 3 mm in thickness in line with the ISO 11405 standard. Ceromer as superstructure was applied to all the infrastructures after their surface treatments according to the selected treatment modality. SBS test was performed to test the effectiveness of surface treatments. A stereomicroscope was used to determine the changes in the surface morphology of specimens. RESULTS: Among the laser modalities and sandblasting, Ho:YAG laser caused the most important increase in the DLS and Ni-Cr-based infrastructures but sandblasting caused the most important increase in the ZrO2 infrastructure. In all the infrastructures, Nd:YAG laser has the least effectiveness, and Er:YAG laser makes an intermediate success. The stereomicroscopy images presented that the applications of laser surface treatments altered the surface in all the infrastructures. CONCLUSIONS: Overall, in current experimental settings, Ho:YAG, Nd:YAG, and Er:YAG lasers, in order of strength, are effective in improving the bonding of ceromer to all the infrastructures. Ho:YAG laser is more effective in the DLS and Ni-Cr-based infrastructures, but sandblasting is more effective in the ZrO2 infrastructure. The studied laser modalities need to be subjected for further studies to determine their appropriate settings and the specifications to be used in prosthodontics. PMID- 27249209 TI - Therapeutic options for cutaneous lupus erythematosus: recent advances and future prospects. AB - INTRODUCTION: Treatment and prevention are of critical importance in patients with cutaneous lupus erythematosus (CLE), as the disease can have a devastating effect on patient well-being and quality of life. AREAS COVERED: We conducted a selective search of the PubMed database for articles published between December 2010 and November 2015. This review encompasses both non-pharmaceutical (photoprotection, smoking cessation, drug withdrawal, and vitamin D replacement) and pharmaceutical (topicals, antimalarials, immunosuppressives, biologics, etc.) interventions used in the treatment of CLE. Expert Commentary: Recent work has expanded our understanding of established therapies as well as introduced new treatments for consideration, though existing medications still prove inadequate for a subset of patients. Changes in trial design may help to alleviate this issue. PMID- 27249216 TI - Attractiveness Compensates for Low Status Background in the Prediction of Educational Attainment. AB - BACKGROUND: People who are perceived as good looking or as having a pleasant personality enjoy many advantages, including higher educational attainment. This study examines (1) whether associations between physical/personality attractiveness and educational attainment vary by parental socioeconomic resources and (2) whether parental socioeconomic resources predict these forms of attractiveness. Based on the theory of resource substitution with structural amplification, we hypothesized that both types of attractiveness would have a stronger association with educational attainment for people from disadvantaged backgrounds (resource substitution), but also that people from disadvantaged backgrounds would be less likely to be perceived as attractive (amplification). METHODS: This study draws on data from the National Longitudinal Study of Adolescent to Adult Health-including repeated interviewer ratings of respondents' attractiveness-and trait-state structural equation models to examine the moderation (substitution) and mediation (amplification) of physical and personality attractiveness in the link between parental socioeconomic resources and educational attainment. RESULTS: Both perceived personality and physical attractiveness have stronger associations with educational attainment for people from families with lower levels of parental education (substitution). Further, parental education and income are associated with both dimensions of perceived attractiveness, and personality attractiveness is positively associated with educational attainment (amplification). Results do not differ by sex and race/ethnicity. Further, associations between perceived attractiveness and educational attainment remain after accounting for unmeasured family-level confounders using a sibling fixed-effects model. CONCLUSIONS: Perceived attractiveness, particularly personality attractiveness, is a more important psychosocial resource for educational attainment for people from disadvantaged backgrounds than for people from advantaged backgrounds. People from disadvantaged backgrounds, however, are less likely to be perceived as attractive than people from advantaged backgrounds. PMID- 27249217 TI - Correction: High-Flux Hemodialysis and High-Volume Hemodiafiltration Improve Serum Calcification Propensity. AB - [This corrects the article DOI: 10.1371/journal.pone.0151508.]. PMID- 27249218 TI - Finite Element Analysis of Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) Surgery Allograft to Predict Endothelial Cell Loss. AB - PURPOSE: To develop high fidelity finite element (FE) models of the Descemet's stripping automated endothelial keratoplasty (DSAEK) allograft to estimate the stress distributions generated on the allograft during its deformed state in popular allograft insertion configurations and qualitatively correlate the stress distributions to postsurgical endothelial cell (EC) loss. MATERIALS AND METHODS: Corneal allograft simulation was performed using ANSYS (Canonsburg, PA, USA) utilizing isotropic nonlinear hyperelastic corneal material properties to evaluate the stress distributions generated on the DSAEK allograft during popular allograft insertion configurations, namely forceps, taco, and double-coil insertion configurations. The gathered FE simulation results were qualitatively compared with published clinical studies to verify the simulation results. RESULTS: The FE simulation results demonstrate that high stress regions predicted by FE model results correctly predict the areas of postsurgical EC loss as published in the studies available in open literature. The FE simulation stress magnitude results suggest that highest EC loss due to mechanical bending trauma occurs in double-coil configuration followed by forceps and then taco configuration. CONCLUSIONS: The results of the presented FE simulation study highlight that allograft regions with high stress distribution demonstrate postsurgical EC loss in clinical studies. The modeling procedures presented in this research can be utilized to develop novel surgical devices/techniques that can modulate the postsurgical EC loss due to mechanical bending trauma and facilitate allograft unfolding inside the AC, thereby improving the results of the DSAEK surgical procedure. PMID- 27249219 TI - Airflow in the Human Nasal Passage and Sinuses of Chronic Rhinosinusitis Subjects. AB - Endoscopic surgery is performed on patients with chronic inflammatory disease of the paranasal sinuses to improve sinus ventilation. Little is known about how sinus surgery affects sinonasal airflow. In this study nasal passage geometry was reconstructed from computed tomographic imaging from healthy normal, pre operative, and post-operative subjects. Transient air flow through the nasal passage during calm breathing was simulated. Subject-specific differences in ventilation of the nasal passage were observed. Velocity magnitude at ostium was different between left and right airway. In FESS, airflow in post-surgical subjects, airflow at the maxillary sinus ostium was upto ten times higher during inspiration. In a Lothrop procedure, airflow at the frontal sinus ostium can be upto four times higher during inspiration. In both post-operative subjects, airflow at ostium was not quasi-steady. The subject-specific effect (of surgery) on sinonasal interaction evaluated through airflow simulations may have important consequences for pre- and post-surgical assessment and surgical planning, and design for improvement of the delivery efficiency of nasal therapeutics. PMID- 27249220 TI - Bio-Anthropological Studies on Human Skeletons from the 6th Century Tomb of Ancient Silla Kingdom in South Korea. AB - In November and December 2013, unidentified human skeletal remains buried in a mokgwakmyo (a traditional wooden coffin) were unearthed while conducting an archaeological investigation near Gyeongju, which was the capital of the Silla Kingdom (57 BCE- 660 CE) of ancient Korea. The human skeletal remains were preserved in relatively intact condition. In an attempt to obtain biological information on the skeleton, physical anthropological, mitochondrial DNA, stable isotope and craniofacial analyses were carried out. The results indicated that the individual was a female from the Silla period, of 155 +/- 5 cm height, who died in her late thirties. The maternal lineage belonged to the haplogroup F1b1a, typical for East Asia, and the diet had been more C3- (wheat, rice and potatoes) than C4-based (maize, millet and other tropical grains). Finally, the face of the individual was reconstructed utilizing the skull (restored from osseous fragments) and three-dimensional computerized modeling system. This study, applying multi-dimensional approaches within an overall bio-anthropological analysis, was the first attempt to collect holistic biological information on human skeletal remains dating to the Silla Kingdom period of ancient Korea. PMID- 27249221 TI - Comparison of Risk Prediction With the CKD-EPI and MDRD Equations in Non-ST Segment Elevation Acute Coronary Syndrome. AB - BACKGROUND: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (GFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. HYPOTHESIS: New CKD-EPI equations improve risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and provide complementary information to the Global Registry of Acute Coronary Events (GRACE) risk score. METHODS: We studied 350 subjects (mean age, 68 +/- 12 years; 70% male) with NSTE-ACS. Estimated GFR was calculated using the MDRD and new CKD-EPI equations based on serum creatinine (SCr) and/or cystatin C (CysC) concentrations obtained within 48 hours of hospital admission. The primary endpoint was all-cause death during follow-up. RESULTS: Over the study period (median, 648 days [interquartile range, 236-1042 days]), 31 patients died (0.05% events per person-year). Decedents had poorer renal-function parameters (P < 0.001). Both CysC-based CKD-EPI equations had the highest areas under the receiver operating characteristic curve for the prediction of all-cause mortality. After multivariate adjustment, only CysC-based CKD-EPI equations were independent predictors of all-cause mortality (CKD-EPISCr CysC , per mL/min/1.73 m(2) : hazard ratio: 0.975, 95% confidence interval: 0.956-0.994, P = 0.009; CKD-EPICysC , per mL/min/1.73 m(2) : hazard ratio: 0.976, 95% confidence interval: 0.959-0.993, P = 0.005). Reclassification analyses showed that only CysC-based CKD-EPI equations improved predictive accuracy of the GRACE risk score. CONCLUSIONS: In patients with NSTE-ACS, CysC-based CKD-EPI equations improved clinical risk stratification for mortality and added complementary prognostic information to the GRACE risk score. PMID- 27249222 TI - Budd-Chiari syndrome: Focus on surgical treatment. AB - Budd-Chiari syndrome (BCS) is caused by an obstruction in the hepatic venous outflow tract at various levels from small hepatic veins to the inferior vena cava (IVC) due to thrombosis or fibrous sequelae. This rare disease mainly affects young adults. Risk factors have been identified and patients often have multiple risk factors. Myeloproliferative diseases of atypical presentation account for nearly 50% of patients in Europe and North America countries. Multistep management is required for such patients. Interventional revascularization and transjugular intrahepatic portosystemic shunt procedure are indicated after initial anticoagulation therapy, whereas IVC plasty using a patch graft is indicated for obstruction of the IVC. Liver transplantation (LT) is usually indicated as a treatment for liver failure despite various treatments. The outcomes of LT are good, with a 5-year survival after LT of nearly 70%. PMID- 27249224 TI - Coinfections with influenza virus and atypical bacteria: Implications for severe outcomes? PMID- 27249223 TI - Influence of Coding Variability in APP-Abeta Metabolism Genes in Sporadic Alzheimer's Disease. AB - The cerebral deposition of Abeta42, a neurotoxic proteolytic derivate of amyloid precursor protein (APP), is a central event in Alzheimer's disease (AD)(Amyloid hypothesis). Given the key role of APP-Abeta metabolism in AD pathogenesis, we selected 29 genes involved in APP processing, Abeta degradation and clearance. We then used exome and genome sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effect of coding variants in these genes as potential susceptibility factors for AD, in a cohort composed of 332 sporadic and mainly late-onset AD cases and 676 elderly controls from North America and the UK. Our study shows that common coding variability in these genes does not play a major role for the disease development. In the single-variant association analysis, the main hits, none of which statistically significant after multiple testing correction (1.9e-4

80 mg/L (8/15 vs. 12/90, P = 0.006) or WBC counts >15x109/L (7/15 vs. 12/90, P = 0.006), indicating that the severity of disease is affected by the presence of the PVL genes. The outcome of the study was defined by 30-day mortality. Four (27%) of the PVL positive patients and four (4%) of the PVL negative patients died within 30 days (P = 0.01, Fisher exact test). Kaplan-Meier survival curves were generated for the PVL positive and PVL negative patient groups, which differed significantly (P = 0.003). Among the patients that died, the mean interval between diagnosis and death was shorter for the PVL positive patients (9.3 +/-5.6 vs. 40.8 +/-6.6 days, P = 0.013). Further analysis within the HAP and VAP patient groups showed that the presence of PVL in MRSA impacted the severity of disease and clinical outcome of HAP, but for VAP the number of patients included in the study was too low. In conclusion, in this single center study in a Chinese hospital the presence of the PVL genes in MRSA impacted the severity of disease and clinical outcome in patients with HAP due to MRSA. PMID- 27249226 TI - Simultaneous removal of ammonia nitrogen and manganese from wastewater using nitrite by electrochemical method. AB - In this work, nitrite was developed to simultaneously remove manganese and ammonia nitrogen from wastewater by the electrochemical method. The characteristics of electrolytic reaction were observed via cyclic voltammograms. Moreover, the mole ratio of nitrite and ammonia nitrogen, voltage, and initial pH value, which affected the removal efficiency of ammonia nitrogen and manganese, were investigated. The results showed that the concentration of ammonia nitrogen in wastewater could be reduced from 120.2 to 6.0 mg L-1, and manganese could be simultaneously removed from 302.4 to 1.5 mg L-1 at initial pH of 8.0, the mole ratios of nitrite and ammonia nitrogen of 1.5:1, and voltage of 20 V direct current electrolysis for 4.0 h. XRD analysis showed that manganese dioxide was deposited on the anode, and manganese was mainly removed in the form of manganese hydroxide precipitation in the cathode chamber. PMID- 27249227 TI - Usefulness of ELISA Methods for Assessing LPS Interactions with Proteins and Peptides. AB - Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram negative bacteria, can trigger severe inflammatory responses during bacterial infections, possibly leading to septic shock. One approach to combatting endotoxic shock is to neutralize the most conserved part and major mediator of LPS activity (lipid A) with LPS-binding proteins or peptides. Although several available assays evaluate the biological activity of these molecules on LPS (e.g. inhibition of LPS-induced TNF-alpha production in macrophages), the development of simple and cost-effective methods that would enable preliminary screening of large numbers of potential candidate molecules is of great interest. Moreover, it would be also desirable that such methods could provide information about the possible biological relevance of the interactions between proteins and LPS, which may enhance or neutralize LPS-induced inflammatory responses. In this study, we designed and evaluated different types of ELISA that could be used to study possible interactions between LPS and any protein or peptide. We also analysed the usefulness and limitations of the different ELISAs. Specifically, we tested the capacity of several proteins and peptides to bind FITC-labeled LPSs from Escherichia coli serotypes O111:B4 and O55:B5 in an indirect ELISA and in two competitive ELISAs including casein hydrolysate (hCAS) and biotinylated polymyxin B (captured by deglycosylated avidin; PMX) as LPS-binding agents in the solid phase. We also examined the influence of pH, detergents and different blocking agents on LPS binding. Our results showed that the competitive hCAS-ELISA performed under mildly acidic conditions can be used as a general method for studying LPS interactions, while the more restrictive PMX-ELISA may help to identify proteins/peptides that are likely to have neutralizing properties in vitro or in vivo. PMID- 27249228 TI - Engineered Metal-Phenolic Capsules Show Tunable Targeted Delivery to Cancer Cells. AB - We engineered metal-phenolic capsules with both high targeting and low nonspecific cell binding properties. The capsules were prepared by coating phenolic-functionalized hyaluronic acid (HA) and poly(ethylene glycol) (PEG) on calcium carbonate templates, followed by cross-linking the phenolic groups with metal ions and removing the templates. The incorporation of HA significantly enhanced binding and association with a CD44 overexpressing (CD44+) cancer cell line, while the incorporation of PEG reduced nonspecific interactions with a CD44 minimal-expressing (CD44-) cell line. Moreover, high specific targeting to CD44+ cells can be balanced with low nonspecific binding to CD44- cells simply by using an optimized feed-ratio of HA and PEG to vary the content of HA and PEG incorporated into the capsules. Loading an anticancer drug (i.e., doxorubicin) into the obtained capsules resulted in significantly higher cytotoxicity to CD44+ cells but lower cytotoxicity to CD44- cells. PMID- 27249229 TI - Epidemiological Investigation and Risk Factors for Cervical Lesions: Cervical Cancer Screening Among Women in Rural Areas of Henan Province China. AB - BACKGROUND This cross-sectional study aimed to investigate the prevalence of cervical lesions and evaluate risk factors for cervical intraepithelial neoplasia (CIN) among women taking part in cervical cancer screening in rural areas of Henan province, China. MATERIAL AND METHODS Cervical cancer screening using the ThinPrep cytologic test (TCT) and gynecologic exam was conducted on 1315 women age 20-68 years in rural areas of Henan province, China. Colposcopy and biopsies were carried out for histopathologic diagnosis when indicated. Univariate and multivariate logistic regressions were performed to evaluate risk factors associated with cervical lesions. RESULTS Among 1315 women screened, CIN prevalence detected by histopathology was 1.22% (0.38% of CIN 1, 0.76% of CIN 2, and 0.08% of CIN 3). Cervical cancer prevalence was 2.66%. Multivariate analysis confirmed risk factors for cervical lesions included older age (the 21-40 age group vs. the 41-66 age group, OR=0.13, 95% CI: 0.03~0.57), postmenopause (OR=0.11, 95% CI: 0.03~0.45), cervical inflammation (OR=0.06, 95% CI: 0.01~0.31), and smoking (OR=6.78, 95% CI: 1.20~38.23). CONCLUSIONS Older age (41-66 years), presence of HPV infection, postmenopause, cervical inflammation, and smoking are strong risk factors for cervical lesions among women in rural areas of Henan province, China. Particular efforts should be made to provide cervical cancer screening for these women. PMID- 27249231 TI - NHE1 expression at wound margins increases time-dependently during physiological healing. AB - Wound repair is an orchestrated process, encompassing the phases of inflammation, proliferation and tissue remodeling. In this context, sodium hydrogen exchanger 1 (NHE1) is crucial to epidermal barrier integrity and acidification. Recently, we found that extracellular pH (pHe) on wound surfaces is dramatically increased initially after barrier disruption, and that pHe decreases gradually during physiological healing. Additionally, we have shown that spatial NHE1-patterns account for pHe-gradients on surfaces of chronic wounds. Here, we show that NHE1 expression is very low at margins initially after wounding and that it increases massively during the time-course of physiolgical healing. This finding is in accordance with the decrease of pHe on wound surfaces, which we reported on in previous works. Thus, we show that NHE1 is an interesting target when it comes to modification of surface pHe on wounds, both acute and chronic, and that NHE1 is time-dependently regulated in physiological healing. PMID- 27249232 TI - Effects of family budgeting responsibility on subjective health status: An empirical study of Japanese wives. AB - We examine whether the decision-making power of Japanese wives affects their health status. Looking at cross-sectional data from the Japanese Panel Survey of Consumers (JPSC) conducted with women, we create a new measure for decision making power based on participation in family budgeting. The data sample covers 1,306 married women aged 25 to 45 years in 2004. We find that Japanese wives are more likely to report good health when they have more responsibility than their husbands for household budgeting. Additionally, having more education or being fully employed increased the probability of reporting "good health" by more than six percentage points. PMID- 27249230 TI - SIRT6 protects against endothelial dysfunction and atherosclerosis in mice. AB - SIRT6 is an important member of sirtuin family that represses inflammation, aging and DNA damage, three of which are causing factors for endothelial dysfunction. SIRT6 expression is decreased in atherosclerotic lesions from ApoE(-/-) mice and human patients. However, the role of SIRT6 in regulating vascular endothelial function and atherosclerosis is not well understood. Here we show that SIRT6 protects against endothelial dysfunction and atherosclerosis. Global and endothelium-specific SIRT6 knockout mice exhibited impaired endothelium-dependent vasorelaxation. Moreover, SIRT6(+/-) haploinsufficient mice fed a high-fat diet (HFD) also displayed impaired endothelium-dependent vasorelaxation. Importantly, SIRT6(+/-); ApoE(-/-) mice after HFD feeding exhibited exacerbated atherosclerotic lesion development, concurrent with increased expression of the proinflammatory cytokine VCAM-1. Loss- and gain-of-SIRT6 function studies in cultured human endothelial cells (ECs) showed that SIRT6 attenuated monocyte adhesion to ECs. RNA-sequencing profiling revealed that SIRT6 overexpression decreased the expression of multiple atherosclerosis-related genes, including proatherogenic gene TNFSF4 (tumor necrosis factor superfamily member 4). Chromatin immunoprecipitation assays showed that SIRT6 decreased TNFSF4 gene expression by binding to and deacetylating H3K9 at TNFSF4 gene promoter. Collectively, these findings demonstrate that SIRT6 play a pivotal role in maintaining endothelial function and increased SIRT6 activity could be a new therapeutic strategy to combat atherosclerotic disease. PMID- 27249233 TI - Functional Role of the Front and Back Legs During a Track Start with Special Reference to an Inverted Pendulum Model in College Swimmers. AB - This study investigated factors that determine the velocity of the center of mass (CM) and flight distance from a track start to devise effective technical and physical training methods. Nine male and 5 female competitive swimmers participated in this study. Kinematics and ground reaction forces of the front and back legs were recorded using a video camera and force plates. The track start was modeled as an inverted pendulum system including a compliant leg, connecting the CM and front edge of the starting block. The increase in the horizontal velocity of the CM immediately after the start signal was closely correlated with the rotational component of the inverted pendulum. This rotational component at hands-off was significantly correlated with the average vertical force of the back plate from the start signal to hands-off (r = .967, P < .001). The flight distance / height was significantly correlated with the average vertical force of the front plate from the back foot-off to front foot off (r = .783, P < .01). The results indicate that the legs on the starting block in the track start play a different role in the behavior of the inverted pendulum. PMID- 27249234 TI - The origin of the cooperativity in the streptavidin-biotin system: A computational investigation through molecular dynamics simulations. AB - Previous experimental study measuring the binding affinities of biotin to the wild type streptavidin (WT) and three mutants (S45A, D128A and S45A/D128A double mutant) has shown that the loss of binding affinity from the double mutation is larger than the direct sum of those from two single mutations. The origin of this cooperativity has been investigated in this work through molecular dynamics simulations and the end-state free energy method using the polarized protein specific charge. The results show that this cooperativity comes from both the enthalpy and entropy contributions. The former contribution mainly comes from the alternations of solvation free energy. Decomposition analysis shows that the mutated residues nearly have no contributions to the cooperativity. Instead, N49 and S88, which are located at the entry of the binding pocket and interact with the carboxyl group of biotin, make the dominant contribution among all the residues in the first binding shell around biotin. PMID- 27249235 TI - Foreword. PMID- 27249236 TI - Anthology of Venezuelan psychiatry. AB - Reception of Psychiatry in Venezuela since the 19th Century to the late 20th Century merits a historical approach. The following work proposes to research some of the very origins of Venezuelan psychiatry and its possible influence on contemporary mental health practice. Through documental research, the early works of local authors from the 19th Century through 20th Century finals: Carlos Arvelo, Lisandro Alvarado, Francisco Herrera Luque, Jose Luis Vethencourt and Jose Solanes, are subjected to study. This journey illustrates a descriptive panoramic view which allows to better comprenhend the current state of our psychiatry. In a brief introduction the most important events are described, since the arrival of Pinel's ideas, followed by the early research paperworks published and the beginnings of the academic teachings of this specialty in Venezuela and displaying the main contemporary research groups thorough the country. PMID- 27249307 TI - IL-27 plasma level in relapsing remitting multiple sclerosis subjects: The double faced cytokine. AB - Interleukin-27 (IL-27) is a member of IL-6/IL-12 cytokine family which possesses pro- and anti-inflammatory properties and participates in the pathogenesis of various autoimmune diseases. In our case-control study, plasma was collected from healthy subjects as control group (n = 40) and patients with relapsing-remitting multiple sclerosis (RRMS) (n = 40), including new identified cases without treatment (n = 12) and those treated with Interferon beta (IFN-beta) (n = 28). The plasma level of IL-27 was assessed by ELISA method. Our results indicated that plasma level of IL-27 in MS patients increased significantly compared to the control subjects (P = 0.027). Furthermore, after parting case group into the two sub-groups, results revealed a significant difference of IL-27 plasma levels between control group and treated patients (P < 0.001), but not about that of between healthy subjects and untreated MS patients (P = 0.259). Also, mean levels of IL-27 in treated and untreated patients showed a significant difference (P = 0.007). These results demonstrate the possible modulation of IL-27 during autoimmune disease in human which may suggest the suppressive or therapeutic role of IL-27 on inflammatory diseases. PMID- 27249237 TI - Cognitive and Other Strategies to Mitigate the Effects of Fatigue. Lessons from Staff Physicians Working in Intensive Care Units. AB - RATIONALE: Fatigue is common among physicians and adversely affects their performance. OBJECTIVES: To identify strategies that attending physicians use when fatigued to maintain clinical performance in the intensive care unit (ICU). METHODS: We conducted a qualitative study using focus groups and structured interviews of attending ICU physicians working in academic centers in Canada. MEASUREMENTS AND MAIN RESULTS: In three focus group meetings, we engaged a total of 11 physicians to identify strategies used to prevent and cope with fatigue. In the focus groups, 21 cognitive strategies were identified and classified into 9 categories (minimizing number of tasks, using techniques to improve retention of details, using a structured approach to patient care, asking for help, improving opportunities for focusing, planning ahead, double-checking, adjusting expectations, and modulating alertness). In addition, various lifestyle strategies were mentioned as important in preventing fatigue (e.g., protecting sleep before call, adequate exercise, and limiting alcohol). Telephone interviews were then conducted (n = 15 physicians) with another group of intensivists. Structured questions were asked about the strategies identified in the focus groups that were most useful during ICU activities. In the interviews, the most useful and frequently used strategies were prioritizing tasks that need to be done immediately and postponing tasks that can wait, working systematically, using a structured approach, and avoiding distractions. CONCLUSIONS: ICU physicians reported using a variety of deliberate cognitive and lifestyle strategies to prevent and cope with fatigue. Given the low cost and intuitive nature of the majority of these strategies, further investigations should be done to better characterize their effectiveness in improving performance. PMID- 27249308 TI - Enhanced conflict-driven cognitive control by emotional arousal, not by valence. AB - Emotion is widely agreed to have two dimensions, valence and arousal. Few studies have explored the effect of emotion on conflict adaptation by considering both of these, which could have dissociate influence. The present study aimed to fill the gap as to whether emotional valence and arousal would exert dissociable influence on conflict adaptation. In the experiments, we included positive, neutral, and negative conditions, with comparable arousal between positive and negative conditions. Both positive and negative conditions have higher arousal than neutral ones. In Experiment 1, by using a two-colour-word Flanker task, we found that conflict adaptation was enhanced in both positive and negative contexts compared to a neutral context. Furthermore, this effect still existed when controlling stimulus-response repetitions in Experiment 2, which used a four colour-word Flanker task. The findings suggest emotional arousal enhances conflict adaptation, regardless of emotional valence. Thus, future studies should consider emotional arousal when studying the effect of emotion on conflict adaptation. Moreover, the unique role of the emotional context in conflict-driven cognitive control is emphasised. PMID- 27249309 TI - Pre-retirement physical working conditions and changes in physical health functioning during retirement transition process. AB - OBJECTIVES: The aim of this study was to examine the association between pre retirement physical working conditions and changes in physical health functioning during the retirement transition process. METHODS: Follow-up survey data were collected among ageing employees of the City of Helsinki, Finland, at three time points: wave 1 (2000-2002), wave 2 (2007) and wave 3 (2012). We focused on those who retired full time due to old age between waves 1 and 3 (N=1658). Exposure to physical workload, occupational environmental hazards, and computer work were divided into quartiles and used as measures of pre-retirement physical working conditions. Physical health functioning was measured by the physical component summary (PCS) of the Short-Form 36 questionnaire. Repeated-measures analysis was used to study the associations. RESULTS: Higher pre-retirement exposure to physical workload and environmental hazards was associated with lower physical health functioning before and after retirement. The differences in functioning narrowed somewhat during the retirement transition process, as physical health functioning in the higher exposure groups improved significantly compared to lower exposure groups. In addition, both high and low exposure to computer work were associated with lower functioning before retirement. However, functioning among those in the lowest exposure group improved during the follow-up whereas in all other exposure groups it declined slightly. This resulted into significantly lower post-retirement functioning among those in the highest as compared to the lower exposure groups. CONCLUSIONS: Retirees with higher exposure to adverse physical working conditions before retirement had lower pre- and post-retirement physical health functioning despite improvements in their functioning during the retirement transition process. PMID- 27249311 TI - 13 nm Exciton Size in (6,5) Single-Wall Carbon Nanotubes. AB - Electron-hole correlation lengths, also termed exciton size, for (6,5) single wall carbon nanotubes (SWNTs) are determined using femtosecond time-resolved pump probe spectroscopy. The phase space filling model is used to obtain the sizes of the first subband exciton in samples of isolated and of bundled SWNTs. The experiments indicate that the exciton size of (13 +/- 3) nm is a factor of 6 higher than previous experimental estimates and theoretical predictions for vacuum suspended SWNTs. This surprising result may be attributed at least in part to the effect of the dielectric environment on exciton sizes and supports recent theoretical findings predicting that screening in SWNTs may enhance rather than reduce electron-hole interactions for separations larger than the tube diameter. Thereby, the work also points to the unique nature of screening and electronic correlations in one-dimensional semiconductors. PMID- 27249312 TI - A novel scatter separation method for multi-energy x-ray imaging. AB - X-ray imaging coupled with recently emerged energy-resolved photon counting detectors provides the ability to differentiate material components and to estimate their respective thicknesses. However, such techniques require highly accurate images. The presence of scattered radiation leads to a loss of spatial contrast and, more importantly, a bias in radiographic material imaging and artefacts in computed tomography (CT). The aim of the present study was to introduce and evaluate a partial attenuation spectral scatter separation approach (PASSSA) adapted for multi-energy imaging. This evaluation was carried out with the aid of numerical simulations provided by an internal simulation tool, Sindbad SFFD. A simplified numerical thorax phantom placed in a CT geometry was used. The attenuation images and CT slices obtained from corrected data showed a remarkable increase in local contrast and internal structure detectability when compared to uncorrected images. Scatter induced bias was also substantially decreased. In terms of quantitative performance, the developed approach proved to be quite accurate as well. The average normalized root-mean-square error between the uncorrected projections and the reference primary projections was around 23%. The application of PASSSA reduced this error to around 5%. Finally, in terms of voxel value accuracy, an increase by a factor >10 was observed for most inspected volumes-of-interest, when comparing the corrected and uncorrected total volumes. PMID- 27249310 TI - Current status of non-viral gene therapy for CNS disorders. AB - INTRODUCTION: Viral and non-viral vectors have been used as methods of delivery in gene therapy for many CNS diseases. Currently, viral vectors such as adeno associated viruses (AAV), retroviruses, lentiviruses, adenoviruses and herpes simplex viruses (HHV) are being used as successful vectors in gene therapy at clinical trial levels. However, many disadvantages have risen from their usage. Non-viral vectors like cationic polymers, cationic lipids, engineered polymers, nanoparticles, and naked DNA offer a much safer option and can therefore be explored for therapeutic purposes. AREAS COVERED: This review discusses different types of viral and non-viral vectors for gene therapy and explores clinical trials for CNS diseases that have used these types of vectors for gene delivery. Highlights include non-viral gene delivery and its challenges, possible strategies to improve transfection, regulatory issues concerning vector usage, and future prospects for clinical applications. EXPERT OPINION: Transfection efficiency of cationic lipids and polymers can be improved through manipulation of molecules used. Efficacy of cationic lipids is dependent on cationic charge, saturation levels, and stability of linkers. Factors determining efficacy of cationic polymers are total charge density, molecular weights, and complexity of molecule. All of the above mentioned parameters must be taken care for efficient gene delivery. PMID- 27249313 TI - Synthetic cathinone pharmacokinetics, analytical methods, and toxicological findings from human performance and postmortem cases. AB - Synthetic cathinones are commonly abused novel psychoactive substances (NPS). We present a comprehensive systematic review addressing in vitro and in vivo synthetic cathinone pharmacokinetics, analytical methods for detection and quantification in biological matrices, and toxicological findings from human performance and postmortem toxicology cases. Few preclinical administration studies examined synthetic cathinone pharmacokinetic profiles (absorption, distribution, metabolism, and excretion), and only one investigated metabolite pharmacokinetics. Synthetic cathinone metabolic profiling studies, primarily with human liver microsomes, elucidated metabolite structures and identified suitable biomarkers to extend detection windows beyond those provided by parent compounds. Generally, cathinone derivatives underwent ketone reduction, carbonylation of the pyrrolidine ring, and oxidative reactions, with phase II metabolites also detected. Reliable analytical methods are necessary for cathinone identification in biological matrices to document intake and link adverse events to specific compounds and concentrations. NPS analytical methods are constrained in their ability to detect new emerging synthetic cathinones due to limited commercially available reference standards and continuous development of new analogs. Immunoassay screening methods are especially affected, but also gas chromatography and liquid-chromatography mass spectrometry confirmation methods. Non-targeted high-resolution-mass spectrometry screening methods are advantageous, as they allow for retrospective data analysis and easier addition of new synthetic cathinones to existing methods. Lack of controlled administration studies in humans complicate interpretation of synthetic cathinones in biological matrices, as dosing information is typically unknown. Furthermore, antemortem and postmortem concentrations often overlap and the presence of other psychoactive substances are typically found in combination with cathinones derivatives, further confounding result interpretation. PMID- 27249314 TI - Baseline-Corrected Second-Order Derivative Electroanalysis Combined With Ultrasound-Assisted Liquid-Liquid Microextraction: Simultaneous Quantification of Fluoroquinolones at Low Levels. AB - A baseline-corrected second-order derivative procedure and a miniaturized sample preparation based on low-density solvent and ultrasound-assisted liquid-liquid microextraction (LDS-UA-LLME) was combined to provide the simultaneous electroanalysis of three fluoroquinolones (FQ) as emerging contaminants (ECs). The enhanced mathematical processing provided the best separation with an accurate measurement of the overlapping peaks during the simultaneous electro oxidation of target FQs that were directly dropped on the surface of carbon nanofiber-modified screen-printed electrodes. The adapted LDS-UA-LLME protocol was the key step involved in the sample preparation, which preconcentrate target analytes from diluted tap water samples with an enrichment factor of around 80*, allowing their quantification at trace levels. This combined feature demonstrated the unique application of an electroanalytical technique for the simultaneous electroanalysis of three FQs in spiked tap water samples, with recovery values remarkably close to 100%. PMID- 27249315 TI - Community Based Psychosocial Education Can Improve Mood Disturbance in Breast Cancer Survivors at Various Stages of Their Recovery. AB - BACKGROUND: Psychosocial distress can contribute to avoidance, refusal, or discontinuation of cancer treatment, which could impact recovery and survival. AIMS: The aim of the present study was to evaluate the effectiveness of a community based psychosocial program on alleviating mood disturbance in breast cancer survivors at different stages of their breast cancer journey. METHOD: A total of 37 women participated in an 8-week psychosocial program at their local community centre. The weekly 3-hour program was delivered in a small group format. Program components included health education, behavioural training, cognitive behavioural therapy, art therapy and stress-management. Questionnaires aimed at assessing psychiatric morbidity and mood adjustment were administered at the beginning of the program (Pre) and at the completion of the program (Post). RESULTS: Group data revealed a significant reduction in psychiatric morbidity and improved psychological adjustment. When participants were divided into degree of psychiatric morbidity (mild, moderate, severe, very severe) a significant reduction in the reporting of anxiety symptoms in the mild, moderate, severe and very severe groups was reported; depression symptoms in the severe and very severe groups were noted, and anger, confusion and somatic symptoms in the mild group were noted. The level of activity was also significantly improved in the very severe group. CONCLUSIONS: A structured community based psychosocial program is beneficial to women struggling to come to terms with the emotional consequences of breast cancer at all stages of recovery. PMID- 27249316 TI - Oxygen Isotope Evidence for Mn(II)-Catalyzed Recrystallization of Manganite (gamma-MnOOH). AB - Manganese is biogeochemically cycled between aqueous Mn(II) and Mn(IV) oxides. Aqueous Mn(II) often coexists with Mn(IV) oxides, and redox reactions between the two (e.g., comproportionation) are well known to result in the formation of Mn(III) minerals. It is unknown, however, whether aqueous Mn(II) exchanges with structural Mn(III) in manganese oxides in the absence of any mineral transformation (similar to what has been reported for aqueous Fe(II) and some Fe(III) minerals). To probe whether atoms exchange between a Mn(III) oxide and water, we use a (17)O tracer to measure oxygen isotope exchange between structural oxygen in manganite (gamma-MnOOH) and water. In the absence of aqueous Mn(II), about 18% of the oxygen atoms in manganite exchange with the aqueous phase, which is close to the estimated surface oxygen atoms (~11%). In the presence of aqueous Mn(II), an additional 10% (for a total of 28%) of the oxygen atoms exchange with water, suggesting that some of the bulk manganite mineral (i.e., beyond surface) is exchanging with the fluid. Exchange of manganite oxygen with water occurs without any observable change in mineral phase and appears to be independent of the rapid Mn(II) sorption kinetics. These experiments suggest that Mn(II) catalyzes manganese oxide recrystallization and illustrate a new pathway by which these ubiquitous minerals interact with their surrounding fluid. PMID- 27249317 TI - Breakthrough in Xenon Capture and Purification Using Adsorbent-Supported Silver Nanoparticles. AB - Rare gas capture and purification is a major challenge for energy, environment, and health applications. Of utmost importance for the nuclear industry, novel separation processes for Xe are urgently needed for spent nuclear fuel reprocessing and nuclear activity monitoring. The recovered, non-radioactive Xe is also of high economic value for lighting, surgical anesthetic, etc. Here, using adsorption and breakthrough experiments and statistical mechanics molecular simulation, we show the outstanding performance of zeolite-supported silver nanoparticles to capture/separate Xe at low concentrations (0.087-100 ppm). We also establish the efficiency of temperature swing adsorption based on such adsorbents for Xe separation from Kr/Xe mixtures and air streams corresponding to off-gases generated by nuclear reprocessing. This study paves the way for the development of novel, cost-efficient technologies relying on the large selectivity/capacity of adsorbent-supported silver nanoparticles which surpass all materials ever tested. PMID- 27249318 TI - Addressing Communicative Participation in Treatment Planning for Adults: A Survey of U.S. Speech-Language Pathologists. AB - PURPOSE: In speech-language pathology, there is increasing attention on participation-focused interventions to optimize participation in valued life roles. The purpose of this study was to investigate how speech-language pathologists (SLPs) in the United States address life participation in therapy programs, as well as their opinions regarding barriers and facilitators to participation-focused intervention. METHOD: An online questionnaire presented case scenarios for aphasia, dysarthria, and laryngectomy to 66 SLPs who have worked with adults. SLPs were asked to write goals and describe therapy activities for the scenarios. The final section of the questionnaire was an open ended question regarding barriers and facilitators to participation-focused intervention. RESULTS: Many SLPs addressed participation in their rationales for therapy; 50% of goals had a participation-focused rationale. However, the goals, activities, and outcomes measures typically focused more on impairment and skill performance. Only 8% of goals specifically referenced participation. Although many SLPs stated that participation-focused intervention is important, they identified many barriers to implementation including time and productivity constraints, limits of clinical settings, and documentation challenges. CONCLUSIONS: There is potential for gaps between SLPs' participation-focused rationale for therapy and activities or outcomes measures that often do not include participation elements. SLPs are interested in participation-focused treatment resources. PMID- 27249319 TI - Penetration Behavior of a Water Droplet into a Cylindrical Hydrophobic Pore. AB - Understanding the dynamics with which a water droplet penetrates a pore is important because of its relationship with transfer phenomena in plants and animals. Using a high-speed camera, we observe the penetration processes of a water droplet into a cylindrical pore on a silicone substrate. The force on the water droplet is generated by dropping the substrate plus water droplet from a height of several centimeters onto an acrylic resin substrate. The penetration characteristics depend on pore size Dp, height of release of a drop h, and the viscosity of the droplet liquid and are classified into the following patterns: spreading, penetration, and breaking. During the process of relaxation to the steady state, various interesting deformation or oscillation phenomena occur. Based on high-speed images, we estimate the interfacial energy DeltaG during the intermediate states and find an energy barrier DeltaG = 1 * 10(-7) J when Dp = 1.0 mm and h = 15 mm for the spreading pattern and DeltaG = 0.7 * 10(-7) J when Dp = 1.0 mm and h = 10 mm for the penetration pattern. Finally, based on a theoretical model considering the driving and suppression factors, we explain the experimentally obtained phase diagram including the separation, penetration, and breaking patterns. PMID- 27249320 TI - A new insight into the isotropic-nematic phase transition in lyotropic solutions of semiflexible polymers: density-functional theory tested by molecular dynamics. AB - Semiflexible polymers in solution are studied for a wide range of both contour length L and persistence length lp as a function of monomer concentration under good solvent conditions. Both density-functional theory (DFT) and molecular dynamics (MD) simulation methods are used, and a very good agreement between both techniques is observed for rather stiff polymers. Evidence for a new mechanism of order parameter fluctuations in the nematic phase is presented, namely collective deformations of bundles of wormlike chains twisted around each other, and the typical wavelengths and amplitudes of these modes are estimated. These long wavelength fluctuations cause a reduction of the order parameter in comparison with the DFT prediction. It is also found that DFT becomes unreliable for rather flexible polymers in predicting that the transition from the isotropic (I)-phase to the nematic (N)-phase still exists at very high monomer concentrations (which in reality does not occur). However, under conditions when DFT is accurate, it provides reliable predictions also for the width of the I-N two-phase coexistence region, which are difficult to obtain from MD in spite of the use of very large systems (up to 500 000 monomers) by means of graphics processing units (GPU). For short and not very stiff chains, a pre-transitional chain stretching is found in the isotropic phase near the I-N-transition, not predicted by theories. A comparison with theoretical predictions by Khokhlov-Semenov, Odijk, and Chen reveals that the scaled transition densities are not simply functions of L/lp only, as these theories predict, but depend on d/lp (where d is the chain diameter) as well. Chain properties in the nematically ordered phase are compared to those of chains confined in tubes, and the deflection length concept is tested. Eventually, some consequences for the interpretation of experiments are spelled out. PMID- 27249322 TI - New ILAE versus previous clinical status epilepticus semiologic classification: Analysis of a hospital-based cohort. AB - OBJECTIVES: In 2015, the International League Against Epilepsy (ILAE) issued a new status epilepticus (SE) classification, including a detailed semiologic axis. This study assesses frequencies of SE forms in a cohort of adult patients, and explores differences and practical implications as compared to a seizure-type bound classification. METHODS: The prospective adult SE registry of the Lausanne University Hospital (CHUV) was considered over 5 years (2011-2015); each SE episode was retrospectively reclassified for its semiology according to the new ILAE scheme. Mortality rates were retrieved for each subgroup of SE. RESULTS: Among 488 SE episodes, according to the seizure-type-bound classification, 230 (47%) had a generalized convulsive, and 29 (6%) had a nonconvulsive SE in coma; both categories overlapped almost perfectly between the two classifications. However, the 84 episodes with focal SE without consciousness impairment and the 141 episodes with consciousness impairment were each translated into two major (and five sub-) categories of the new ILAE classification, having markedly different mortality rates. In addition, of 140 episodes labeled as focal motor SE according to the new classification, 54% had concomitant consciousness impairment, whereas 46% did not; again, mortality rates were heterogeneous. SIGNIFICANCE: Although generalized convulsive and nonconvulsive SE in coma show an almost perfect correspondence across SE semiologic classifications, focal SE is markedly heterogeneous and appears to be better reflected in the new classification, offering more clinically relevant subdivisions, also differing in mortality rates. This refined knowledge may allow the development of clinical prognostic scores that are more precise than existing tools, and should be taken into account for epidemiologic studies. PMID- 27249323 TI - Demonstrating Medical Student Competency in Palliative Care: Development and Evaluation of a New Objective Structured Clinical Examination Station. AB - BACKGROUND: The observed structured clinical examination (OSCE) is an important tool to assess clinical competencies; however, there are no reported palliative care OSCEs for medical student assessment. OBJECTIVE: We aimed to develop, implement, and evaluate the characteristics of a palliative care OSCE for fourth year medical students. METHODS: We created a representative case and a checklist of 14 history items from three core palliative care competency domains. Subjects were fourth-year medical students who had completed our school's longitudinal palliative care curriculum. Measurements were students' scores compiled from the standardized patient's (SP) tally of the checklist results. We determined inter rater reliability between the SP and a remote observer. Measurements included the difficulty and discrimination index, internal consistency reliability, factor analysis, and relationships between palliative care scores and composite seven station OSCE scores. RESULTS: In the implementation year, 95 students scored an average of 74% (standard deviation [SD] = 13%) on the 14 history items. There was 95% agreement in ratings on items between the SP and the remote observer. The Cronbach's alpha was 0.53, demonstrating moderate internal consistency. The palliative care scores correlated with overall OSCE communication scores (R = 0.29, p = 0.01) and history scores (R = 0.61, p = 0.01). CONCLUSIONS: A new OSCE to assess palliative care competencies was feasible to implement with high inter rater reliability, evidence supporting validity, and moderate internal consistency. We believe this OSCE would prove useful to assess students' primary palliative care competency and to evaluate curricula in palliative care. PMID- 27249321 TI - Suppressor of IKKE is an essential negative regulator of pathological cardiac hypertrophy. AB - Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKE (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID- 27249325 TI - Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators. AB - INTRODUCTION: Sphingosine-1-phosphate (S1P) receptor modulators, of which one has received marketing approval and several others are in clinical development, display promising potential in the treatment of a spectrum of autoimmune diseases. AREAS COVERED: Administration of S1P1 receptor modulators leads to functional receptor antagonism triggering sustained inhibition of the egress of lymphocytes from lymphoid organs. First-dose administration is associated with transient cardiovascular effects. We compiled and discussed available pharmacokinetic, pharmacodynamic, and safety data of selective and non-selective S1P receptor modulators that were investigated in recent years. EXPERT OPINION: The safety profile of S1P receptor modulators is considered better than other classes of immunomodulators and was further improved by the development of up titration regimens to mitigate first-dose effects. S1P receptor modulators display similar pharmacodynamic effects but have very different pharmacokinetic profiles. Drugs with a rapid elimination are of interest in case of opportunistic infections or pregnancy, whereas the need of re-initiation of up-titration in case of treatment interruption can present a challenge. PMID- 27249324 TI - Substitution and Complementarity of Alcohol and Cannabis: A Review of the Literature. AB - BACKGROUND: Whether alcohol and cannabis are used as substitutes or complements remains debated, and findings across various disciplines have not been synthesized to date. OBJECTIVE: This article is a first step towards organizing the interdisciplinary literature on alcohol and cannabis substitution and complementarity. METHOD: Electronic searches were performed using PubMed and ISI Web of Knowledge. Behavioral studies of humans with "alcohol" (or "ethanol") and "cannabis" (or "marijuana") and "complement(*)" (or "substitut(*)") in the title or as a keyword were considered. Studies were organized according to sample characteristics (youth, general population, clinical and community-based). These groups were not set a priori, but were informed by the literature review process. RESULTS: Of the 39 studies reviewed, 16 support substitution, ten support complementarity, 12 support neither and one supports both. Results from studies of youth suggest that youth may reduce alcohol in more liberal cannabis environments (substitute), but reduce cannabis in more stringent alcohol environments (complement). Results from the general population suggest that substitution of cannabis for alcohol may occur under more lenient cannabis policies, though cannabis-related laws may affect alcohol use differently across genders and racial groups. CONCLUSIONS: Alcohol and cannabis act as both substitutes and complements. Policies aimed at one substance may inadvertently affect consumption of other substances. Future studies should collect fine grained longitudinal, prospective data from the general population and subgroups of interest, especially in locations likely to legalize cannabis. PMID- 27249326 TI - CT Findings for Detecting the Presence of Gangrenous Ischemia in Cholecystitis. AB - OBJECTIVE: The objective of our study was to evaluate the diagnostic accuracy of CT in differentiating gangrenous cholecystitis from uncomplicated cholecystitis and healthy gallbladders. MATERIALS AND METHODS: We performed a retrospective review of 308 patients with histologically proven gangrenous cholecystitis who underwent preoperative CT 1 month before gallbladder removal over a 4-year period. Two readers who were blinded to the histologic diagnosis independently recorded CT features of and overall likelihood of gangrenous cholecystitis on a 5 point scale (1, definitely absent; 5, definitely present). Ratings were dichotomized such that a diagnosis was considered present at a rating of 4 or 5 and considered absent at lower ratings. Interobserver variability for individual CT findings was also assessed. RESULTS: Patients had gangrenous cholecystitis (n = 28), acute cholecystitis (n = 98), chronic cholecystitis (n = 118), or healthy gallbladders (n = 64). Multivariate analysis showed that CT findings of gallbladder distention greater than 4.0 cm (odds ratio [OR], 9.63; p < 0.01), mural striation (OR, 11.39; p < 0.01), and decreased mural enhancement (OR, 3.55; p < 0.05) independently predicted gangrenous cholecystitis. Using these CT features, the diagnosis of gangrenous cholecystitis was made with a specificity of 93.9% and 89.6% for readers 1 and 2, respectively, and accuracy of 90.9% and 87.0%, respectively. Good agreement was seen between the two readers with respect to gallbladder distention greater than 4.0 cm (kappa = 0.77) and decreased mural enhancement (kappa = 0.64). CONCLUSION: A markedly distended gallbladder associated with decreased wall enhancement is highly specific for gangrenous cholecystitis. PMID- 27249327 TI - And Walls Shall Break: The ISBER 2016 Annual Meeting and Exhibits. PMID- 27249328 TI - A Complex Prime Numerical Representation of Amino Acids for Protein Function Comparison. AB - Computationally assessing the functional similarity between proteins is an important task of bioinformatics research. It can help molecular biologists transfer knowledge on certain proteins to others and hence reduce the amount of tedious and costly benchwork. Representation of amino acids, the building blocks of proteins, plays an important role in achieving this goal. Compared with symbolic representation, representing amino acids numerically can expand our ability to analyze proteins, including comparing the functional similarity of them. Among the state-of-the-art methods, electro-ion interaction pseudopotential (EIIP) is widely adopted for the numerical representation of amino acids. However, it could suffer from degeneracy that two different amino acid sequences have the same numerical representation, due to the design of EIIP. In light of this challenge, we propose a complex prime numerical representation (CPNR) of amino acids, inspired by the similarity between a pattern among prime numbers and the number of codons of amino acids. To empirically assess the effectiveness of the proposed method, we compare CPNR against EIIP. Experimental results demonstrate that the proposed method CPNR always achieves better performance than EIIP. We also develop a framework to combine the advantages of CPNR and EIIP, which enables us to improve the performance and study the unique characteristics of different representations. PMID- 27249329 TI - Quantum mechanical modeling the emission pattern and polarization of nanoscale light emitting diodes. AB - Understanding of the electroluminescence (EL) mechanism in optoelectronic devices is imperative for further optimization of their efficiency and effectiveness. Here, a quantum mechanical approach is formulated for modeling the EL processes in nanoscale light emitting diodes (LED). Based on non-equilibrium Green's function quantum transport equations, interactions with the electromagnetic vacuum environment are included to describe electrically driven light emission in the devices. The presented framework is illustrated by numerical simulations of a silicon nanowire LED device. EL spectra of the nanowire device under different bias voltages are obtained and, more importantly, the radiation pattern and polarization of optical emission can be determined using the current approach. This work is an important step forward towards atomistic quantum mechanical modeling of the electrically induced optical response in nanoscale systems. PMID- 27249331 TI - Riluzole exerts transient modulating effects on cortical and axonal hyperexcitability in ALS. AB - Riluzole is an established therapy for amyotrophic lateral sclerosis (ALS), although its effects are modest, prolonging survival by three months on average. While the neuroprotective effects of riluzole appear to be mediated by inhibition of glutaminergic transmission and antagonization of Na+ channel function, the duration of these effects remains to be elucidated. Consequently, the present study combined assessment of cortical and peripheral function to determine the longitudinal effects of riluzole in ALS patients. Assessment of cortical function by threshold tracking transcranial magnetic stimulation (TMS) combined with peripheral nerve function excitability studies were longitudinally undertaken on 19 sporadic ALS patients, with assessment occurring at baseline, four, eight, and 12 weeks post riluzole initiation. Baseline results were compared to 31 healthy controls. Results showed that, at baseline, cortical hyperexcitability was a feature of ALS as indicated by a marked reduction in averaged short interval intracortical inhibition [SICI] (3.6 +/- 6.9%, p < 0.0001) and cortical silent period duration (p < 0.05) as well as an increase in motor evoked potential amplitude (p < 0.05). Riluzole therapy resulted in individual patient increase in SICI of 4.3% (p < 0.01) and 5.2% (p < 0.01) at four and eight weeks, respectively. At a peripheral level, riluzole therapy lead to a transient increase at four weeks in the relative refractory period (p < 0.05), superexcitability (p < 0.05) and late subexcitability (p < 0.05), all of which returned to baseline levels eight weeks after initiation of riluzole. In conclusion, the present study has established that riluzole exerts transient effects on cortical and axonal hyperexcitability, potentially accounting for the modest clinical effectiveness in ALS. PMID- 27249330 TI - Associations Between Cannabis Use and Physical Health Problems in Early Midlife: A Longitudinal Comparison of Persistent Cannabis vs Tobacco Users. AB - IMPORTANCE: After major policy changes in the United States, policymakers, health care professionals, and the general public seek information about whether recreational cannabis use is associated with physical health problems later in life. OBJECTIVE: To test associations between cannabis use over 20 years and a variety of physical health indexes at early midlife. DESIGN, SETTING, AND PARTICIPANTS: Participants belonged to a representative birth cohort of 1037 individuals born in Dunedin, New Zealand, in 1972 and 1973 and followed to age 38 years, with 95% retention (the Dunedin Multidisciplinary Health and Development Study). We tested whether cannabis use from ages 18 to 38 years was associated with physical health at age 38, even after controlling for tobacco use, childhood health, and childhood socioeconomic status. We also tested whether cannabis use from ages 26 to 38 years was associated with within-individual health decline using the same measures of health at both ages. EXPOSURES: We assessed frequency of cannabis use and cannabis dependence at ages 18, 21, 26, 32, and 38 years. MAIN OUTCOMES AND MEASURES: We obtained laboratory measures of physical health (periodontal health, lung function, systemic inflammation, and metabolic health), as well as self-reported physical health, at ages 26 and 38 years. RESULTS: The 1037 study participants were 51.6% male (n = 535). Of these, 484 had ever used tobacco daily and 675 had ever used cannabis. Cannabis use was associated with poorer periodontal health at age 38 years and within-individual decline in periodontal health from ages 26 to 38 years. For example, cannabis joint-years from ages 18 to 38 years was associated with poorer periodontal health at age 38 years, even after controlling for tobacco pack-years (beta = 0.12; 95% CI, 0.05 0.18; P <.001). Additionally, cannabis joint-years from ages 26 to 38 years was associated with poorer periodontal health at age 38 years, even after accounting for periodontal health at age 26 years and tobacco pack-years (beta = 0.10; 95% CI, 0.05-0.16; P <.001) However, cannabis use was unrelated to other physical health problems. Unlike cannabis use, tobacco use was associated with worse lung function, systemic inflammation, and metabolic health at age 38 years, as well as within-individual decline in health from ages 26 to 38 years. CONCLUSIONS AND RELEVANCE: Cannabis use for up to 20 years is associated with periodontal disease but is not associated with other physical health problems in early midlife. PMID- 27249332 TI - Toward Design Principles for Diffusionless Transformations: The Frustrated Formation of Co-Co Bonds in a Low-Temperature Polymorph of GdCoSi2. AB - Diffusionless (or displacive) phase transitions allow inorganic materials to show exquisite responsiveness to external stimuli, as is illustrated vividly by the superelasticity, shape memory, and magnetocaloric effects exhibited by martensitic materials. In this Article, we present a new diffusionless transition in the compound GdCoSi2, whose origin in frustrated bonding points toward generalizable design principles for these transformations. We first describe the synthesis of GdCoSi2 and the determination of its structure using single crystal X-ray diffraction. While previous studies based on powder X-ray diffraction assigned this compound to the simple CeNi1-xSi2 structure type (space group Cmcm), our structure solution reveals a superstructure variant (space group Pbcm) in which the Co sublattice is distorted to create zigzag chains of Co atoms. DFT calibrated Huckel calculations, coupled with a reversed approximation Molecular Orbital (raMO) analysis, trace this superstructure to the use of Co-Co isolobal bonds to complete filled 18 electron configurations on the Co atoms, in accordance with the 18-n rule. The formation of these Co-Co bonds is partially impeded, however, by a small degree of electron transfer from Si-based electronic states to those with Co-Co sigma* character. The incomplete success of Co-Co bond creation suggests that these interactions are relatively weak, opening the possibility of them being overcome by thermal energy at elevated temperatures. In fact, high-temperature powder and single crystal X-ray diffraction data, as well as differential scanning calorimetry, indicate that a reversible Pbcm to Cmcm transition occurs at about 380 K. This transition is diffusionless, and the available data point toward it being first-order. We expect that similar cases of frustrated interactions could be staged in other rare earth-transition metal-main group phases, providing a potentially rich source of compounds exhibiting diffusionless transformations and the unique properties these transitions mediate. PMID- 27249333 TI - AirJump: Using Interfaces to Instantly Perform Simultaneous Extractions. AB - Analyte isolation is an important process that spans a range of biomedical disciplines, including diagnostics, research, and forensics. While downstream analytical techniques have advanced in terms of both capability and throughput, analyte isolation technology has lagged behind, increasingly becoming the bottleneck in these processes. Thus, there exists a need for simple, fast, and easy to integrate analyte separation protocols to alleviate this bottleneck. Recently, a new class of technologies has emerged that leverages the movement of paramagnetic particle (PMP)-bound analytes through phase barriers to achieve a high efficiency separation in a single or a few steps. Specifically, the passage of a PMP/analyte aggregate through a phase interface (aqueous/air in this case) acts to efficiently "exclude" unbound (contaminant) material from PMP-bound analytes with higher efficiency than traditional washing-based solid-phase extraction (SPE) protocols (i.e., bind, wash several times, elute). Here, we describe for the first time a new type of "exclusion-based" sample preparation, which we term "AirJump". Upon realizing that much of the contaminant carryover stems from interactions with the sample vessel surface (e.g., pipetting residue, wetting), we aim to eliminate the influence of that factor. Thus, AirJump isolates PMP-bound analyte by "jumping" analyte directly out of a free liquid/air interface. Through careful characterization, we have demonstrated the validity of AirJump isolation through comparison to traditional washing-based isolations. Additionally, we have confirmed the suitability of AirJump in three important independent biological isolations, including protein immunoprecipitation, viral RNA isolation, and cell culture gene expression analysis. Taken together, these data sets demonstrate that AirJump performs efficiently, with high analyte yield, high purity, no cross contamination, rapid time-to-isolation, and excellent reproducibility. PMID- 27249334 TI - The multiple mini-interviews as a predictor of peer evaluations during clinical training in medical school. AB - BACKGROUND: Multiple Mini-Interviews (MMI) is an admissions tool being used for more than a decade by medical schools worldwide to assess non-cognitive skills. In Israel, in addition to the MMI tool, two questionnaires are given to the candidates. It has been necessary to find a relevant criterion to examine the predictive validity of the MMI test. The measure developed in this study was a peer assessment tool which was filled out during clerkship. AIMS: The study aims at evaluating the predictive validity of the MMI and two questionnaires when compared with the peer assessment tool. METHOD: Ninety nine fourth-year medical students were included in this study. All of them went through the MMI test before the beginning of their studies. The students participated in two clinical rotations and were divided into 10 groups, each consisting of 9-12 students. This study is based on assessments given to 99 students. Every member of a group evaluated his fellow members on a number of attribute. The questionnaire included 10 statements, related to a particular attributes. In addition two concluding questions were included. Pearson correlations were used to test the relationships between pre-admission variables (MMI and two questionnaires) and the peer assessments. RESULTS: Statistically significant, moderate correlations between the general MOR and MIRKAM scores and the sum of the questionnaire assessments were 0.39 and 0.37, respectively (P-value <0.05). CONCLUSIONS: The study provides important evidence for the validity of the MMI. Additional studies are required to reevaluate the predicted validity of the MMI. PMID- 27249335 TI - Hydrogen-like Wannier-Mott Excitons in Single Crystal of Methylammonium Lead Bromide Perovskite. AB - A thorough investigation of exciton properties in bulk CH3NH3PbBr3 perovskite single crystals was carried out by recording the reflectance, steady-state and transient photoluminescence spectra of submicron volumes across the crystal. The study included an examination of the spectra profiles at various temperatures and laser excitation fluencies. The results resolved the first and second hydrogen like Wannier-Mott exciton transitions at low temperatures, from which the ground state exciton's binding energy of 15.33 meV and Bohr radius of ~4.38 nm were derived. Furthermore, the photoluminescence temperature dependence suggested dominance of delayed exciton emission at elevated temperatures, originating from detrapping of carriers from shallow traps or/and from retrapping of electron-hole pairs into exciton states. The study revealed knowledge about several currently controversial issues that have an impact on functionality of perovskite materials in optoelectronic devices. PMID- 27249336 TI - Mitotic phosphorylation of SOX2 mediated by Aurora kinase A is critical for the stem-cell like cell maintenance in PA-1 cells. AB - Transcription factor SOX2 is multiple phosphorylated. However, the kinase and the timing regulating SOX2 phosphorylation remains poorly understood. Here we reported mitotic phosphorylation of SOX2 by Aurora kinase A (AURKA). AURKA inhibitors (VX680, Aurora kinase Inhibitor I) but not PLK1 inhibitors (BI2536, CBB2001) eliminate the mitotic phosphorylation of SOX2. Consistently, siRNA inhibition of AURKA can eliminate mitotic SOX2 phosphorylation. Ser220 and Ser251 are two sites that identified for mitotic phosphorylation on SOX2. Moreover, SOX2 mutants (S220A and S251A) can promote SOX2 induced OCT4 re-expression in differentiated cells. These findings reveal a novel regulation mechanism of SOX2 phosphorylation mediated by AURKA in mitosis and its function in stem cell pluripotency maintenance in cancer cells. PMID- 27249337 TI - Concordance of Brain and Core Temperature in Comatose Patients After Cardiac Arrest. AB - Comatose patients after cardiac arrest should receive active targeted temperature management (TTM), with a goal core temperature of 32-36 degrees C for at least 24 hours. Small variations in brain temperature may confer or mitigate a substantial degree of neuroprotection, which may be lost at temperatures near 37 degrees C. The purpose of this study was to define the relationship between brain and core temperature after cardiac arrest through direct, simultaneous measurement of both. We placed intracranial monitors in a series of consecutive patients hospitalized for cardiac arrest at a single tertiary care facility within 12 hours of return of spontaneous circulation to guide postcardiac arrest care. We compared the absolute difference between brain and core (esophageal or rectal) temperature measurements every hour for the duration of intracranial monitoring and tested for a lag between brain and core temperature using the average square difference method. Overall, 11 patients underwent simultaneous brain and core temperature monitoring for a total of 906 hours of data (Median 95; IQR: 15-118 hours per subject). On average, brain temperature was 0.34C degrees (95% confidence interval [CI] 0.31-0.37) higher than core temperature. In 7% of observations, brain temperature exceeded the measured core temperature >=1 degrees C. Brain temperature lagged behind core temperature by 0.45 hours (95% CI = -0.27-1.27 hours). Brain temperature averages 0.34 degrees C higher than core temperature after cardiac arrest, and is more than 1 degrees C higher than core temperature 7% of the time. This phenomenon must be considered when carrying out TTM to a goal core temperature of <36 degrees C. PMID- 27249338 TI - A Longitudinal Assessment of Associations between Adolescent Environment, Adversity Perception, and Economic Status on Fertility and Age of Menarche. AB - PURPOSE: Perceptions of environmental adversity and access to economic resources in adolescence can theoretically affect the timing of life history transitions and investment in reproductive effort. Here we present evidence of correlations between variables associated with subjective extrinsic mortality, economic status, and reproductive effort in a nationally representative American population of young adults. METHODS: We used a longitudinal database that sampled American participants (N >= 1,579) at four points during early adolescence and early adulthood to test whether perceptions of environmental adversity and early economic status were associated with reproductive effort. RESULTS: We found that subjectively high ratings of environmental danger and low access to economic resources in adolescence were significantly associated with an earlier age of menarche in girls and earlier, more robust fertility in young adulthood. CONCLUSION: While energetics and somatic condition remain as possible sources of variation, the results of this study support the hypothesis that perceptions of adversity early in life and limited access to economic resources are associated with differences in reproductive effort and scheduling. How these factors may covary with energetics and somatic condition merits further investigation. PMID- 27249339 TI - Histidine-Directed Arylation/Alkenylation of Backbone N-H Bonds Mediated by Copper(II). AB - Chemical modification of proteins and peptides represents a challenge of reaction design as well as an important biological tool. In contrast to side-chain modification, synthetic methods to alter backbone structure are extremely limited. In this communication, copper-mediated backbone N-alkenylation or N arylation of peptides and proteins by direct modification of natural sequences is described. Histidine residues direct oxidative coupling of boronic acids at the backbone NH of a neighboring amino acid. The mild reaction conditions in common physiological buffers, at ambient temperature, are compatible with proteins and biological systems. This simple reaction demonstrates the potential for directed reactions in complex systems to allow modification of N-H bonds that directly affect polypeptide structure, stability, and function. PMID- 27249340 TI - Direct interaction of avermectin with epidermal growth factor receptor mediates the penetration resistance in Drosophila larvae. AB - With the widespread use of avermectins (AVMs) for managing parasitic and agricultural pests, the resistance of worms and insects to AVMs has emerged as a serious threat to human health and agriculture worldwide. The reduced penetration of AVMs is one of the main reasons for the development of the resistance to the chemicals. However, the detailed molecular mechanisms remain elusive. Here, we use the larvae of Drosophila melanogaster as the model organism to explore the molecular mechanisms underlying the development of penetration resistance to AVMs. We clearly show that the chitin layer is thickened and the efflux transporter P-glycoprotein (P-gp) is overexpressed in the AVM-resistant larvae epidermis. We reveal that the activation of the transcription factor Relish by the over-activated epidermal growth factor receptor (EGFR)/AKT/ERK pathway induces the overexpression of the chitin synthases DmeCHS1/2 and P-gp in the resistant larvae. Interestingly, we discover for the first time, to the best of our knowledge, that AVM directly interacts with EGFR and leads to the activation of the EGFR/AKT/ERK pathway, which activates the transcription factor Relish and induces the overexpression of DmeCHS1/2 and P-gp. These findings provide new insights into the molecular mechanisms underlying the development of penetration resistance to drugs. PMID- 27249342 TI - Recent advances in dynamic m6A RNA modification. AB - The identification of m(6)A demethylases and high-throughput sequencing analysis of methylated transcriptome corroborated m(6)A RNA epigenetic modification as a dynamic regulation process, and reignited its investigation in the past few years. Many basic concepts of cytogenetics have been revolutionized by the growing understanding of the fundamental role of m(6)A in RNA splicing, degradation and translation. In this review, we summarize typical features of methylated transcriptome in mammals, and highlight the 'writers', 'erasers' and 'readers' of m(6)A RNA modification. Moreover, we emphasize recent advances of biological functions of m(6)A and conceive the possible roles of m(6)A in the regulation of immune response and related diseases. PMID- 27249344 TI - Getting to the heart of an unusual kinetochore. AB - The Mis12 complex forms the central scaffold of the kinetochore and serves to bridge the chromatin and microtubule-binding activities of the inner and outer layers, respectively. Two recent studies provide new structural insights into the formation of this complex, and highlight some intriguing adaptations found in the Drosophila kinetochore. PMID- 27249345 TI - An asterid flower from neotropical mid-Tertiary amber. AB - Fossils preserved in amber may provide significant palaeoevolutionary and biogeographical data regarding the evolution of life on Earth(1). Although amber is particularly noted for its detailed preservation of arthropods, the same degree of preservation can be found for vascular plant remains(2). Mid-Tertiary Dominican amber is a rich source for such fossils, and representatives of several angiosperm families have been described. However, no fossilized examples of the large asterid plant clade have yet been reported. Here we describe the first fossil neotropical flowers found in amber from a representative of the asterids. The asterids are one of the largest lineages of flowering plants, containing groups such as the sunflower, potato, coffee and mint families, totalling over 80,000 species(3). The new fossils are only known as flowers, more precisely corollas with stamens and styles. We here describe them as a new species, Strychnos electri sp. nov, in the plant family Loganiaceae (Gentianales). PMID- 27249343 TI - A closed conformation of the Caenorhabditis elegans separase-securin complex. AB - The protease separase plays a key role in sister chromatid disjunction and centriole disengagement. To maintain genomic stability, separase activity is strictly regulated by binding of an inhibitory protein, securin. Despite its central role in cell division, the separase and securin complex is poorly understood at the structural level. This is partly owing to the difficulty of generating a sufficient quantity of homogeneous, stable protein. Here, we report the production of Caenorhabditis elegans separase-securin complex, and its characterization using biochemical methods and by negative staining electron microscopy. Single particle analysis generated a density map at a resolution of 21-24 A that reveals a close, globular structure of complex connectivity harbouring two lobes. One lobe matches closely a homology model of the N-terminal HEAT repeat domain of separase, whereas the second lobe readily accommodates homology models of the separase C-terminal death and caspase-like domains. The globular structure of the C. elegans separase-securin complex contrasts with the more elongated structure previously described for the Homo sapiens complex, which could represent a different functional state of the complex, suggesting a mechanism for the regulation of separase activity through conformational change. PMID- 27249346 TI - Plant synthetic biology for molecular engineering of signalling and development. AB - Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions. PMID- 27249347 TI - Artificial remodelling of alternative electron flow by flavodiiron proteins in Arabidopsis. AB - In photosynthesis, linear electron transport from water to nicotinamide adenine dinucleotide phosphate (NADP(+)) cannot satisfy the ATP/NADPH production stoichiometry required by the Calvin-Benson cycle. Cyclic electron transport (CET) around photosystem I (PSI) and pseudocyclic electron transport (pseudoCET) can produce ATP without the accumulation of NADPH. Flavodiiron proteins (Flv) are the main mediator of pseudoCET in photosynthetic organisms, spanning cyanobacteria to gymnosperms. However, their genes are not conserved in angiosperms. Here we explore the possibility of complementing CET with Flv dependent pseudoCET in the angiosperm Arabidopsis thaliana. We introduced FlvA and FlvB genes from the moss Physcomitrella patens into both wild-type (WT) Arabidopsis and the proton gradient regulation 5 (pgr5) mutant, which is defective in the main pathway of CET. We measured rates of pseudoCET using membrane inlet mass spectrometry, along with several photosynthetic parameters. Flv expression significantly increased rates of pseudoCET in the mutant plants, particularly at high light intensities, and partially restored the photosynthetic phenotype. In WT plants, Flv did not compete with PGR5-dependent CET during steady-state photosynthesis, but did form a large electron sink in fluctuating light. We conclude that flavodiiron proteins can help to protect the photosystems in Arabidopsis under fluctuating light, even in the presence of CET. PMID- 27249348 TI - Arabidopsis NAC transcription factor JUB1 regulates GA/BR metabolism and signalling. AB - Gibberellins (GAs) and brassinosteroids (BRs) are important phytohormones that control plant development and responses to environmental cues by involving DELLA proteins and BRASSINAZOLE-RESISTANT1 (BZR1) respectively as key transcription factors. Here, we reveal a new role for JUNGBRUNNEN1 (JUB1) as a transcriptional regulator of GA/BR signalling in Arabidopsis thaliana. JUB1 directly represses the hormone biosynthesis genes GA3ox1 and DWARF4 (DWF4), leading to reduced levels of GAs and BRs and typical GA/BR deficiency phenotypes exhibiting short hypocotyls, dwarfism, late flowering and male sterility. JUB1 also directly represses PHYTOCHROME INTERACTING FACTOR4 (PIF4), a transcription factor connecting hormonal and environmental stimuli. On the other hand, JUB1 activates the DELLA genes GA INSENSITIVE (GAI) and RGA-LIKE 1 (RGL1). In addition, BZR1 and PIF4 act as direct transcriptional repressors upstream of JUB1, establishing a negative feedback loop. Thus, JUB1 forms the core of a robust regulatory module that triggers DELLA accumulation, thereby restricting cell elongation while concomitantly enhancing stress tolerance. PMID- 27249349 TI - Multi-country evidence that crop diversification promotes ecological intensification of agriculture. AB - Global food security requires increased crop productivity to meet escalating demand(1-3). Current food production systems are heavily dependent on synthetic inputs that threaten the environment and human well-being(2,4,5). Biodiversity, for instance, is key to the provision of ecosystem services such as pest control(6,7), but is eroded in conventional agricultural systems. Yet the conservation and reinstatement of biodiversity is challenging(5,8,9), and it remains unclear whether the promotion of biodiversity can reduce reliance on inputs without penalizing yields on a regional scale. Here we present results from multi-site field studies replicated in Thailand, China and Vietnam over a period of four years, in which we grew nectar-producing plants around rice fields, and monitored levels of pest infestation, insecticide use and yields. Compiling the data from all sites, we report that this inexpensive intervention significantly reduced populations of two key pests, reduced insecticide applications by 70%, increased grain yields by 5% and delivered an economic advantage of 7.5%. Additional field studies showed that predators and parasitoids of the main rice pests, together with detritivores, were more abundant in the presence of nectar-producing plants. We conclude that a simple diversification approach, in this case the growth of nectar-producing plants, can contribute to the ecological intensification of agricultural systems. PMID- 27249350 TI - Coupling of histone methylation and RNA processing by the nuclear mRNA cap binding complex. AB - In eukaryotes, genes are transcribed into pre-mRNAs that are subsequently processed into mature mRNAs by adding a 5'-cap and a 3'-polyA tail and splicing introns. Pre-mRNA processing involves their binding proteins and processing factors, whereas gene transcription often involves chromatin modifiers. It has been unclear how the factors involved in chromatin modifications and RNA processing function in concert to control mRNA production. Here, we show that in Arabidopsis thaliana, the evolutionarily conserved nuclear mRNA cap-binding complex (CBC) forms multi-protein complexes with a conserved histone 3 lysine 4 (H3K4) methyltransferase complex called COMPASS-like and a histone 3 lysine 36 (H3K36) methyltransferase to integrate active histone methylations with co transcriptional mRNA processing and cap preservation, leading to a high level of mature mRNA production. We further show that CBC is required for H3K4 and H3K36 trimethylation, and the histone methyltransferases are required for CBC-mediated mRNA cap preservation and efficient pre-mRNA splicing at their target loci, suggesting that these factors are functionally interdependent. Our study reveals novel roles for histone methyltransferases in RNA-processing-related events and provides mechanistic insights into how the 'downstream' RNA CBC controls eukaryotic gene transcription. PMID- 27249352 TI - Photosynthesis: Rewiring an angiosperm. PMID- 27249351 TI - Transposon-derived small RNA is responsible for modified function of WRKY45 locus. AB - Transposable elements (TEs) are an important source for generating small interfering RNAs (siRNAs) in plants and animals. Although TE-siRNA-induced silencing of TEs by RNA-directed DNA methylation (RdDM) in the maintenance of genome integrity has been intensively studied, it is unknown whether this type of silencing occurs in suppressing endogenous non-TE genes during host-pathogen interactions. Here we show that a TE-siRNA, TE-siR815, causes opposite functions for the two alleles, WRKY45-1 and WRKY45-2, of the WRKY45 transcription factor in rice resistance to Xanthomonas oryzae pv. oryzae, which causes the most devastating bacterial disease in rice worldwide. Expression of WRKY45-1, but not WRKY45-2, generated TE-siR815, which in turn repressed ST1, an important component in WRKY45-mediated resistance, by RdDM. Suppression of ST1 abolished WRKY45-mediated resistance leading to pathogen susceptibility. These results suggest that TE-siR815 contributes to the natural variation of the WRKY45 locus and TE-siR815-induced suppression of ST1 results in the negative role of WRKY45-1 but positive role of WRKY45-2 in regulating disease resistance. PMID- 27249353 TI - Photomorphogenesis: When blue meets red. PMID- 27249354 TI - Systemic silencing: Mobile sRNA stabilizes genomes. PMID- 27249355 TI - Small RNA biogenesis: Novel roles of an RNase III enzyme. PMID- 27249356 TI - Signalling: Yin-yang hormonal crosstalk. PMID- 27249357 TI - Monitoring plant functional diversity from space. PMID- 27249358 TI - Immunity: NLR population control. PMID- 27249359 TI - Photosynthesis: Seasonal shift. PMID- 27249360 TI - Ecophysiology: Desert roots. PMID- 27249361 TI - Defence: Switching targets. PMID- 27249362 TI - In search of anechoic discussion. PMID- 27249363 TI - Test-retest reliability of rapid whole body and compartmental fat volume quantification on a widebore 3T MR system in normal-weight, overweight, and obese subjects. AB - PURPOSE: To measure the test-retest reliability of rapid (<15 min) whole body and visceral fat volume quantification in normal and obese subjects on a widebore 3T MR system and compare it with conventional manual segmentation. MATERIALS AND METHODS: Thirty participants (body mass index [BMI] 20.1-48.6 kg/m2 ) underwent two whole-body magnetic resonance imaging (MRI) examinations on a widebore 3T machine using a 2-point Dixon technique. Phase sensitive reconstruction and intensity inhomogeneity correction produced quantitative datasets of total adipose tissue (TAT), abdominal subcutaneous adipose tissue (ASAT), and visceral adipose tissue (VAT). The quantification was performed automatically using nonrigid atlas-based segmentation and compared with manual segmentation (SliceOmatic). RESULTS: The mean TAT was 31.74 L with a coefficient of variation (CV) of 0.79% and a coefficient of repeatability (CR) of 0.49 L. The ASAT was 7.92 L with a CV of 2.98% and a CR of 0.46 L. There was no significant difference in the semiautomated and manually segmented VAT (P = 0.73) but there were differences in the reliability of the two techniques. The mean semiautomated VAT was 2.56 L, CV 1.8%, and CR 0.09 L compared to the mean manually segmented VAT of 3.12 L, where the CV was 6.3% and the CR was 0.39 L. CONCLUSION: Rapid semiautomated whole body and compartmental fat volume quantification can be derived from a widebore 3T system, for a range of body sizes including obese patients, with "almost perfect" test-retest reliability. J. Magn. Reson. Imaging 2016;44:1464-1473. PMID- 27249364 TI - Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice. AB - Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-beta-amyloid antibody. Our data suggest a biomarker strategy for the early detection of beta-amyloid-related abnormalities. PMID- 27249369 TI - Sequence Evolution and Expression of the Androgen Receptor and Other Pathway Related Genes in a Unisexual Fish, the Amazon Molly, Poecilia formosa, and Its Bisexual Ancestors. AB - The all-female Amazon molly (Poecilia formosa) originated from a single hybridization of two bisexual ancestors, Atlantic molly (Poecilia mexicana) and sailfin molly (Poecilia latipinna). As a gynogenetic species, the Amazon molly needs to copulate with a heterospecific male, but the genetic information of the sperm-donor does not contribute to the next generation, as the sperm only acts as the trigger for the diploid eggs' embryogenesis. Here, we study the sequence evolution and gene expression of the duplicated genes coding for androgen receptors (ars) and other pathway-related genes, i.e., the estrogen receptors (ers) and cytochrome P450, family19, subfamily A, aromatase genes (cyp19as), in the Amazon molly, in comparison to its bisexual ancestors. Mollies possess-as most other teleost fish-two copies of the ar, er, and cyp19a genes, i.e., aralpha/arbeta, eralpha/erbeta1, and cyp19a1 (also referred as cyp19a1a)/cyp19a2 (also referred to as cyp19a1b), respectively. Non-synonymous single nucleotide polymorphisms (SNPs) among the ancestral bisexual species were generally predicted not to alter protein function. Some derived substitutions in the P. mexicana and one in P. formosa are predicted to impact protein function. We also describe the gene expression pattern of the ars and pathway-related genes in various tissues (i.e., brain, gill, and ovary) and provide SNP markers for allele specific expression research. As a general tendency, the levels of gene expression were lowest in gill and highest in ovarian tissues, while expression levels in the brain were intermediate in most cases. Expression levels in P. formosa were conserved where expression did not differ between the two bisexual ancestors. In those cases where gene expression levels significantly differed between the bisexual species, P. formosa expression was always comparable to the higher expression level among the two ancestors. Interestingly, erbeta1 was expressed neither in brain nor in gill in the analyzed three molly species, which implies a more important role of eralpha in the estradiol synthesis pathway in these tissues. Furthermore, our data suggest that interactions of steroid signaling pathway genes differ across tissues, in particular the interactions of ars and cyp19as. PMID- 27249371 TI - Sodium Reduction--Saving Lives by Putting Choice Into Consumers' Hands. PMID- 27249370 TI - 17beta-Estradiol Protects Skeletal Myoblasts From Apoptosis Through p53, Bcl-2, and FoxO Families. AB - 17beta-Estradiol (E2 ) protects several nonreproductive tissues from apoptosis, including skeletal muscle. Previously, we showed that E2 at physiological concentrations prevented apoptosis induced by H2 O2 in skeletal myoblasts, reverting PKCdelta, JNK, and p66Shc activation and exerting a beneficial action over mitochondria. Since genomic actions underlying the regulation of nuclear gene transcription are a common property of this steroid, the present work characterizes the transcriptional activity modulated by E2 to exert its antiapoptotic effect. We report that E2 protects skeletal myoblasts against apoptosis induced by H2 O2 modulating p53 and FoxO transcription factors and then their target genes Bcl-2, Bim, Puma, PERP, and MDM2, without affecting Noxa gene. The results presented in this work support the notion that the transcription factors FoxO and p53 coordinate apoptosis in C2C12 cells, and deepens our knowledge about a putative molecular mechanism by which E2 exerts beneficial effects against oxidative stress in skeletal myoblasts. J. Cell. Biochem. 118: 104-115, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27249372 TI - Rh Nanoparticle Anchoring on Metal Phosphates: Fundamental Aspects and Practical Impacts on Catalysis. AB - Metal phosphates stabilize Rh nanoparticles on their surface via Rh-O-P bonds, in contrast to the Rh-O-M bonds formed on metal oxides (MOx ). The local structure, electronic structure, and redox properties of Rh nanoparticles anchored on metal phosphates, and their practical impacts on catalysis, are reviewed based on recent publications from the author's research group. Because of the covalency of the Rh-O-P bond, Rh oxide is readily reduced to metallic Rh having a higher catalytic activity, whereas Rh oxide on metal oxide supports is more difficult to reduce with an increase of the anchoring strength. Furthermore, Rh metal shows a higher tolerance to reoxidation when supported on metal phosphates because the Rh O-P bond is preserved under reducing atmospheres. The electron deficiency of Rh metal is another feature that affects its catalytic properties, and the extent of the electron deficiency can be tuned by replacing the metal in the metal phosphate with one of higher basicity. Further impacts on practical performance (thermal stability, poisoning stability, and lean NOx purification) in automobile catalyst applications are also described. PMID- 27249373 TI - Reduced Virulence of Azoxystrobin-Resistant Zymoseptoria tritici Populations in Greenhouse Assays. AB - The development of resistance to multiple fungicide classes is currently limiting disease management options for many pathogens, while the discovery of new fungicide classes may become less frequent. In light of this, more research is needed to quantify virulence trade-offs of fungicide resistance in order to more fully understand the implications of fungicide resistance on pathogen fitness. The purpose of this study was to measure the virulence of azoxystrobin-resistant and -sensitive Zymoseptoria tritici populations collected from North and South Willamette Valley, Oregon, in 2012 and 2015. Inoculum mixtures of known fungicide resistant phenotypes were used to simulate natural field conditions, where multiple genotypes exist and interact in close proximity. Six greenhouse inoculations were conducted over 2 years, and virulence of the isolate mixtures was evaluated in planta. We considered virulence to be "the degree of pathology caused by the organism" and visually estimated the percent area of leaf necrosis as a measure of virulence. In greenhouse conditions, a consistent association of reduced virulence with azoxystrobin-resistant Z. tritici isolate mixtures was observed. North Willamette Valley and South Willamette Valley populations did not differ in virulence. PMID- 27249375 TI - In Memoriam, Professor Hanfa Zou, 1961-2016. PMID- 27249374 TI - Localization of Acrolein-Lysine Adduct in Fibrovascular Tissues of Proliferative Diabetic Retinopathy. AB - PURPOSE: To determine the presence of Nepsilon-(3-formyl-3,4-dehydropiperidino) lysine adduct (FDP-Lys), unsaturated aldehyde acrolein-derived lipoxidation end product, in fibrovascular tissues obtained from patients with proliferative diabetic retinopathy (PDR). METHODS: Fibrovascular tissues were collected from 11 eyes of 11 patients with PDR and paraffin-embedded tissue sections were prepared. Tissue localization of FDP-Lys was studied by immunohistochemistry. Signal intensity was quantified by two masked evaluators and graded into three discrete categories. The relationship between FDP-Lys staining and vascular density was analyzed. In addition, subcellular localization of FDP-Lys was studied by immunofluorescent microscopy. The impact of acrolein on cell viability and proliferation was assessed and the expression level of heme oxygenase-1 (HO-1) mRNA was quantified by real-time polymerase chain reaction (PCR) in cultured retinal microvascular endothelial cells. RESULTS: In fibrovascular tissues, FDP Lys staining was found in vascular components containing CD34-positive cells and alpha smooth muscle actin (alpha-SMA)-positive cells, and clusters of rabbit anti glial fibrillary acid protein (GFAP)-positive cells. Immunofluorescent staining depicted subcellular localization of FDP-Lys in the nucleus and cytoplasm of the cells. Morphological analysis revealed that fibrovascular tissues with FDP-Lys staining in vascular components showed high vascular density. Exposure of cultured endothelial cells to high concentration of acrolein resulted in the decrease of cell viability and proliferation, whereas lower concentration of acrolein increased cell viability and proliferation. Sublethal concentration of acrolein upregulated HO-1 mRNA expression in retinal microvascular endothelial cells. CONCLUSIONS: The current data demonstrated the presence of FDP-Lys in fibrovascular tissues and indicate its involvement in fibrovascular proliferation in PDR. PMID- 27249376 TI - Glycomics and Glycoproteomics 2016. PMID- 27249379 TI - Bardo Terrorist attack : psychological support units : Assessment and Recommendations 9 months after ... PMID- 27249380 TI - Ki-67: role in diagnosis, prognosis and follow-up after treatment of breast cancers. AB - AIM: To evaluate the literature data about diagnostic value, prognosis value and interest in follow-up of Ki-67 antibody after treatment for breast cancer. METHODS: We performed a literature search in pubmed using the keywords : Ki-67, anti-Ki-67, breast cancer, prognosis, proliferation, chemotherapy, hormone therapy. RESULTS: Ki-67 is routinely used as a static marker of proliferative activity and in follow-up-monitoring before and after treatment by chemotherapy and more recently hormonotherapy. Ki-67 was also used at a cut-off of 14% to differentiate between luminal A and B breast cancers. A high Ki-67 expression is probably related to a poorer prognosis but also a better response to neoadjuvant chemo and/or targeted therapy. More recently, genomic analysis is more reliable to classify the molecular breast cancer subtypes avoiding the possible cases of discordant Ki-67 rate. Ki-67 is also interesting in predicting histological response to neoadjuvant chemo and hormone therapy. CONCLUSION: Ki-67 evaluated by immunohistochemistry is important in routine in countries without bimolecular plateforms despite technical insufficiencies. When available, genomic grading is better to classify molecular subtypes and determine breast cancer prognosis in adjuvant and neoadjuvant setting. PMID- 27249381 TI - Screening for viral hepatitis C in a young Tunisian population (more than 175,000 recruits). AB - BACKGROUND: In front of the considerable impact of the viral hepatitis C, the prevention is more than ever a priority, based essentially on the screening. AIM: We realized an epidemiological study in a population of young recruits with the aim of considering prevalence of anti-hepatitis C Virus (anti-HCV) antibodies, describing its epidemiological evolution and establishing a cartography of the viral hepatitis C in Tunisia. METHODS: Epidemiological retrospective study of prevalence was realized from the data of the screening of anti-HCV antibodies from 2003 till 2012 of all the young recruits suggested to be incorporated for the national service or suggested to be recruited as career soldier. The study was exhaustive concerning 175 322 young and healthy male adults aged between 20 and 30 years old, originating from all parts of Tunisia. The screening was realized by third and fourth generation ELISA tests then validated by Immunoblot. RESULTS: The prevalence was 0.11% and the confirmed prevalence was 0.07%. The positive subjects were mainly between 20 and 25 years old (82.32%) and 91.05% were detected within the framework of their incorporations to the national service. The lowest prevalence was 0.07% in 2004, and the highest was 0.17% in 2011, without a significant tendency in the increase or in the decrease during the period of study (r = 0.857 ; p = 0.564). The screening of anti-VHC antibodies had an unequal geographical distribution according to a North-South decreasing gradient. The highest proportions were registered in the North-West (23.23%) and the District of Tunis (22.73%), contrary to the South-East which was weakly affected (3.54%). The governorates with the highest proportions were Tunis (19.19%), Bizerte (11.62%) and Jendouba (8.59%), the governorates of Monastir and Tataouine were weakly affected (0.51%). CONCLUSION: Prevalence of anti-HCV antibodies in the young and male Tunisian population was weak, stable without significant tendency in the increase or in the decrease from 2003 till 2012, characterized by an unequal geographical distribution according to a North-South decreasing gradient. PMID- 27249377 TI - Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment. AB - As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings. PMID- 27249382 TI - Reclassification of gastrointestinal mesenchymal tumors. AB - BACKGROUND: Gastrointestinal stromal tumors - commonly called GISTs - are rare; yet, they represent an important type of mensenchymal tumors arising within the gastrointestinal tract. The acronym GIST was introduced in 1998 to define a well established pathological entity which bears a highly specific marker called KIT (CD117). Scientific interest for these tumors in recent years is mainly due to the progress in identification by immunohistochemistry and the advent of targeted molecular therapy. AIM: To reclassify mesenchymal tumors of the digestive tract using advanced immunophenotyping. METHODS: We examined the digestive tissue tumors operated at the Principal Military Hospital of Instruction of Tunis over a 19-year period from 1992 to 2011. RESULTS: We collected 22 cases of benign mesenchymal tumors of the digestive tract. Tumors were initially diagnosed as leiomyomas (4 cases), schwannomas (2 cases), gastrointestinal stromal tumors (14 cases), a leiomyoblastoma and a mesenchymal tumor with fusiform cells. The immunohistochemical study has allowed to correct some diagnoses and, in one case, the block has been exhausted. In total, we selected 18 cases of gastrointestinal stromal tumor, a tumors. The final diagnosis of GIST was confirmed by the positivity of C-kit or DOG1. CONCLUSIONS: The combined use of C-kit and DOG1 ensures accurate diagnosis of GIST. The DOG1 has allowed us to detect the 3 stromal tumors negative for C-kit. This antibody has achieved a diagnostic gain of 15 %. The rate of GIST tumors labeled increased from 71 % to 86 % among mesenchymal tumors. PMID- 27249383 TI - Impact of gamete cell quality on the outcome of intracytoplasmic sperm injection. AB - BACKGROUND: the quality of the gametes used for an intracytoplasmic microinjection of spermatozoide is a significant factor which can influence pregnancy rates. AIM: To assess the effect of conventional sperm parameters, origin of spermatozoa and oocyte quality on pregnancy rate in ICSI. METHODS: A retrospective and comparative study of 500 women who underwent ICSI cycle during the study period from January 2004 to December 2005. Conventional sperm parameters (count, motility and morphology) and oocyte quality (mature and immatures oocytes) was compared in two groups of patients: Those achieving a pregnancy: The "pregnancy+" group and those failing to have a pregnancy: The "pregnancy-" group. RESULTS: Among the conventional sperm parameters, only spermatozoa count after preparation was significantly higher in "pregnancy+" group (p=0,02). We found significantly more pregnancies in ejaculated and epididymal sperm groups than in the testicular one (p<10-3). The number of oocyte retrieved was significantly higher in "pregnancy+" group (13,9+/-7 vs 10,6+/- 7,6 ; p<10-3) with mainly mature oocyte (metaphaseII) (9,1+/-5,5 vs 6,6+/-5,4 ; p<10 3). Analysis of ROC curve and logistic regression study show that for mature oocyte, the most discriminative cut-off for predicting pregnancy is 4 (OR=2,1 ; LR+=6,7 ;IC[1 ;1,4] ; p0,009). CONCLUSION: Conventional parameters of ejaculated sperm have almost no influence on pregnancy rates in ICSI. Testicular sperm seem to have worse results. The number of oocytes retrieved and the proportion of mature oocytes (metaphaseII) affect markedly the prognosis. PMID- 27249384 TI - Status dystonicus in childhood. AB - BACKGROUND: Status Dystonicus is a rare complication of dystonia. It is a life threatening disorder that needs urgent treatment.The aim of this study is to describe clinical features, management and follow up of children with Status Dystonicus. METHODS: - We conducted a retrospective study over an 8-year period including all patients diagnosed with Status Dystonicus. Clinical characteristics, etiologies and management were analyzed. RESULTS: - Ten patients were included. Main features of Status Dystonicus were a severe generalized dystonia with vegetative signs. Laryngeal spasm and swallowing disorders were observed in 4 cases. Several treatments such as Levodopa, Anticholinergics, Baclofen, Benzodiazepines and Neuroleptics were tried. Mechanical ventilation was required in 4 cases. Two patients died due to rhabdomyolysis and respiratory failure. Others returned to their pre-Status Dystonicus. CONCLUSION: - Status Dystonicus is a life threatening condition that needs an urgent management on an intensive care unit. In fact, patients with Status Dystonicus can develop respiratory failure and metabolic complications.On the basis of our experience, we delineated a therapeutic approach in which the patient with Status Dystonicus needs supportive care, specific therapy of dystonia and intravenous sedative treatment. PMID- 27249385 TI - Pharmacokinetik population of methotrexate in tunisian population with acute lymphoblastic leukemia. AB - BACKGROUND: The use of high dose of MTX in the treatment of the leukemia is actually better controlled by renal preparation, control of plasma concentrations and administration of folinic acid. However, High dose MTX has been proven to cause substantial toxicity and have high intra-and inter-patient variability. Population pharmacokinetic analysis is a useful tool for identification of sources of pharmacokinetic variability during anticancer drug development and can aid the design of alternative dosing regimens to enhance their efficacy and safety. AIM: The aim of our study is to developed and validate a population pharmacokinetics model of our population. We hereby describe the clinical covariates (age, sex and clearance of the creatinine) that influence MTX pharmacokinetic for predicting optimal dose to reduce MTX toxicity. METHOD: It is a prospective study achieved between January 2005 to January 2012 in the Service of Clinical Pharmacology. Including 273 patients treated for acute lymphocytic leukaemia 2582 plasma concentration was achieved. The data have been analyzed with Nonmem(c) software (non linear regression to mixed effect). RESULTS: The age of our patients varied from 2 to 23 years with an average of 13 years. The patients received high dose MTX therapy (1 to 8 g/m2) in 24 hours infusion every 15 days. Three compartiment models describe the pharmacokinetic of MTX. The most important covariables affecting the model were clearance of the creatinine, age and weight. We obtained a good correlation between the predicted and the observed concentrations. CONCLUSION: The development of population pharmacokinetics model of MTX allows us to propose a therapeutic diagram adapted to every patient according to its morphological and pharmacological features while taking in consideration the therapeutic objective. PMID- 27249386 TI - Contribution of Polymerase Chain Reaction for detection of malaria in Tunisia. AB - BACKGROUND: In Tunisia, detection of Plasmodium in asymptomatic individuals from endemic countries is a critical measure in national program of malaria eradication. The screening is based on microscopic examination of thick and thin blood smears. However, the performance of this diagnosis is closely related to the experience of biologist and the parasitaemia. AIM: The objective of this study was to evaluate the contribution of the PCR in the screening of malaria. METHODS: This prospective study involved 260 students from malaria endemic areas who were screened for malaria between september 2011 and june 2013. Each subject had a blood sample which was examined for malaria by microscopy and nested multiplex PCR. RESULTS: PCR detected the presence of Plasmodium in 13 blood samples (5%). While microscopy was positive only in nine cases (3.5%). The discordances involved five negative samples at microscopy and which were positive in PCR and a negative sample in PCR which was positive at microscopy. A mixed infection with Plasmodium falciparum and Plasmodium malariae was identified by PCR. For this case, microscopy diagnosed only Plasmodium falciparum specie. CONCLUSION: PCR is more efficient than microscopy in detecting low parasitaemia ; particularly observed in asymptomatic subjects. This technique allows to reduce asymptomatic carriage of Plasmodium and reduce the risk of a resumption of transmission of malaria in our country. PMID- 27249387 TI - The tunneled catheter for haemodialysis: about 52 cases. AB - BACKGROUND: Vascular access is a basic and essential tool required for performing renal replacement therapy in end stage renal disease. AIM: To study the indications of tunneled catheter (KTT) in hemodialysis (HD), identify complications related to the use of KTT and contributing factors, assess the survival and performance of the technique. INTRODUCTION: The making of a vascular access is an angular piece for adequate HD and in good conditions. In this context the KTT may be an alternative. METHODS: A retrospective study of 52 KTT placed in 49 patients collected in the department of Nephrology Dialysis and Renal Transplantation in RABTA Tunis between 2008 and 2011. RESULTS: The average age of our patients was 55.58 years +/- 13.5 years, their Sex ratio was 0.79. The Thirty of our patients were diabetic, 46.2% had hypertension and 21.2% had underlying cardiac disease. The mean duration of HD was 1111.35 days or 37 months. The most common indication of KTT was the absence of arteriovenous fistula in 65.4% of cases, other indications were: short survival (30.7%), the exhaustion of venous capital (34.6%), mediacalcosis (34.6%) and immunosuppression (36.5%). The right internal jugular vein was the choice of insertion site with 78.8%. The overall incidence of immediate complications was 19.2%. Among our patients, 31.4% had a dysfunction. The period of HD represent the risk factor for dysfunction KTT (p = 0.006).An infectious complication was observed in 29% of cases. The median time to onset of infection was 190.83 days. Staphylococcus was isolated in 40% of cases. The average duration of use of KTT was 238 days. The only single factor determining the survival of KTT was the number of KTT put in the same patient. CONCLUSION: More than a quarter of the population are dialyzed through a catheter. Despite concerted efforts, much remains to be done for the confection at time of a permanent vascular access. PMID- 27249388 TI - Impact of the components of metabolic syndrome on survival in a group of hemodialysis. AB - BACKGROUND: Metabolic syndrome is defined by the combination of high blood pressure, dyslipidemia, central obesity and a state of insulin resistance. Its prevalence is high in hemodialysis. AIM: The aim of this work is to see the impact of metabolic syndrome on mortality and morbidity in our hemodialysis patients. METHODS: This is a retrospective study of 120 chronic hemodialysis patients. The metabolic syndrome was investigated according to the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Survival was estimated based on each parameter of the metabolic syndrome. A comparison by sex was performed for the following parameters: age, diabetes, hypertension, obesity, waist circumference, dyslipidemia, coronary artery disease and heart failure. RESULTS: Forty chronic hemodialysis patients with metabolic syndrome have been the subject of this study. The mean age was 55.97 years and the sex ratio was 1.88. Seventy percent had diabetes and 90% were hypertensive. Coronary artery disease was present in 57.5% of cases of heart failure in 52.5% of cases. There was no significant difference in 10 years survival depending on the presence of each component of the metabolic syndrome. The study by sex showed no significant difference except for hyper LDL cholesterol. CONCLUSION: Our study showed no impact of the components of metabolic syndrome on survival. There is a high prevalence of cardiovascular complications but causality with the metabolic syndrome could not be demonstrated. PMID- 27249389 TI - Smoking prevalence in a factory in the region of Sousse- Tunisia. AB - BACKGROUND: Smoking is a public health problem because of its high prevalence and its serious consequences at all levels. AIM: The aim of this study was to determine the prevalence of smoking among workers in a private company and describe the characteristics of smokers to guide prevention efforts. METHODS: It is a cross-sectional study conducted in 2010 among all employees of a private company. Data collection was done by a questionnaire administered by interview. RESULTS: The participation rate was 90.4%. All smokers were men, with a prevalence of active smoking among men of 57.9%. The mean age of smokers was 33.2 +/- 8 years, significantly lower than nonsmokers. The comparison between smokers and nonsmokers according to occupational category showed a statistically significant difference. Among smokers, 43.6% were in the contemplation stage and 46.3% at the stage of preparation for smoking cessation. CONCLUSION: An intervention for prevention and fight against smoking in the workplace should be established for the promotion of employee health. PMID- 27249390 TI - Assessment of cochlear effects and extra-auditory disorders in male rats exposed repetitively to low noise. AB - BACKGROUND: The noise is considered as a factor of environmental stress, causing a wide range of health effects such as acoustic, cardiovascular, nervous and endocrine systems. PURPOSE: The present study was conducted to examine the affects of repeated exposure to noise on the peripheral auditory system, adrenal gland and heart tissue. METHOD: The White strain rats "Wistar" were exposed to chronic and repetitive exposure noise at two different intensity levels of 70 and 85dB (A). The noise level was generated by the Audacity(r) software to an octave band noise (8616 kHz). The sound exposure duration was 6 hr/day, 5 days per week for 3 months. Quantitative and qualitative investigations were performed by using electron microscopy. The ganglion neuron counting was examined via light microscopy. RESULTS: The results show that exposure to sound intensities 70 and 85 dB (A) for long periods, lead to changes in the morphological structure of the cochlea (inner ear), adrenal cortex and cardiac tissue which involve cell disruption which over time can lead to pathological effects. CONCLUSION: This study provides morphological evidence that repetitive exposure noise at moderate sound levels to 70 and 85 dB (A) induces changes in the peripheral auditory system, the adrenal cortex and heart tissue. PMID- 27249391 TI - The incidence of serious adverse events in a tunisian hospital: a retrospective medical record review study. AB - AIM: To describe the epidemiology of serious adverse events (SAE) reported in the division of internal medicine at the Mongi Slim university hospital in Tunis, to analyze their causes and contributing factors and compare them to that reported in literature so as to establish prevention strategies when these events were deemed preventable. Methods This retrospective study collected the medical records of randomly selected 500 index hospitalizations. Records review was conducted in two stages: a primary review that aimed to detect hospitalizations where a SAE was likely to have occurred then a secondary review which purpose was to confirm the presence of the SAE, to determine its nature and its preventability. RESULTS: SAE were detected in 5.2% of hospitalizations with a preventability of 57.7%. These events were responsible for a prolongation in 27.0% of hospitalizations and disability in 15.4% of cases. They were the cause of admission in 42.9% of hospitalizations in which a SAE occurred. The SAE consisted in adverse drug events in 73.0% of cases, healthcare-associated infections in 19.0% of cases, non-surgical procedures in 4% of cases and pressure ulcers in 4.0% of cases. Age and number of comorbidities were identified as the main risk factors for the occurrence of SAE. CONCLUSION: Awareness of the extent and severity of the problem of iatrogenesis is necessary because it is a prerequisite to establishing a culture of patient safety among caregivers. PMID- 27249392 TI - Predictive factors of mortality in Fournier's gangrene. AB - BACKGROUND: Fournier's Gangrene is a rare but serious condition accounting for a high death rate. Several predictive factors of mortality have been reported from retrospective series but more often these factors vary from one study to another. AIM: The aim of this work is to assess the clinical and therapeutic characteristics of patients treated for Fournier's gangrene in order to determine the predictive factors of mortality. METHODS: The study enrolled retrospectively all patients admitted in the surgery 'B' unit of Charles Nicolle hospital for Fournier's gangrene during the period ranging between January, 1st, 2000 and December, 31st, 2010. The diagnosis of Fournier's gangrene has been retained each time a tissue necrosis has been noted in perineum, whether during physical examination or intraoperatively. For all patients, clinical variables and treatments were collected. A comparative study was carried out between the group of survivors and deceased. RESULTS: Forty one patients have been included. The univariate analysis identified the following predictive factors of mortality: extension of lesions outside the perineum (p=0,002), severe sepsis and/or a septic shock (p=0,006), heart rate greater than 90/min (p=0,001), white blood cell count higher than 20000/mm3 (p=0,043) and urea level higher than 7 mmol/l (p=0,009). The multivariate analysis retained the extension of gangrene beyond the perineum as an independent predictive factor of mortality (p=0,004). CONCLUSION: Improving prognosis of Fournier's gangrene requires early diagnosis ahead of the extension of lesions beside the perineum which is associated with a higher mortality risk despite optimal care and treatment. PMID- 27249393 TI - Endoscopic argon plasma coagulation for the treatment of Watermelon stomach. PMID- 27249394 TI - Multiple autoimmune syndrome. About a case. PMID- 27249396 TI - An unusual mediastinal malignant tumor: atypical thymic carcinoid. PMID- 27249395 TI - Fahr's disease revealed by psychiatric symptoms like schizo-affective disorder. PMID- 27249397 TI - Renal metastases: Rare manifestation of lung carcinoma. PMID- 27249398 TI - An under recognized skin complication of diabetes: A diagnostic challenge. PMID- 27249399 TI - Infective endocarditis mimicking a systemic vasculitis. PMID- 27249400 TI - Idiopathic pulmonary haemosiderosis in adult: a rare cause of recurrent hemoptysis. PMID- 27249401 TI - Usefulness and limitations of balloon-occluded transcatheter arterial chemoembolization using miriplatin for patients with four or fewer hepatocellular carcinoma nodules. AB - AIM: The aim of this study is to clarify the usefulness and limitations of balloon-occluded transcatheter arterial chemoembolization (B-TACE) using miriplatin for patients with four or fewer hepatocellular carcinoma (HCC) nodules. METHODS: We studied 47 nodules in 30 consecutive patients who received miriplatin by B-TACE to treat HCC with four or fewer nodules per patient. The treatment effect was evaluated using the Response Evaluation Criteria in Cancer of the Liver. RESULTS: Nodules were divided according to the presence or absence of portal vein visualization during B-TACE. In the presence group, dynamic computed tomography at 3 months post-therapy showed Response Evaluation Criteria in Cancer of the Liver treatment effect (TE) 4 in 88% (14/16), TE3 in 0% (0/16), TE2 in 0% (0/16), TE1 in 12% (2/16), and objective response in 88% of nodules. In the absence group, the results were TE4 in 35% (11/31), TE3 in 13% (4/31), TE2 in 26% (8/31), TE1 in 26% (8/31), and objective response decreased to 48% of nodules. In addition to typical hypervascular nodules, we treated three nodules with irregular ring enhancement that predicted poorly differentiated HCC and four nodules that included a hypoenhancement area that predicted well to moderately differentiated HCC. All irregular ring enhancement nodules achieved TE4. Other nodules that were predicted to be well to moderately differentiated HCC did not have portal vein visualization during B-TACE and could not achieve TE4. CONCLUSION: Balloon-occluded transcatheter arterial chemoembolization is a useful technique for treatment of classical hypervascular HCC, and portal vein visualization during the B-TACE procedure may provide more favorable local control. PMID- 27249402 TI - Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Active Pharmaceutical Ingredients. AB - Although roughly 40% of pharmaceuticals being developed are poorly water soluble, this class of drugs lacks a formulation strategy capable of producing high loads, fast dissolution kinetics, and low energy input. In this work, a novel bottom-up approach is developed for producing and formulating nanocrystals of poorly water soluble active pharmaceutical ingredients (APIs) using core-shell composite hydrogel beads. Organic phase nanoemulsion droplets stabilized by polyvinyl alcohol (PVA) and containing a model hydrophobic API (fenofibrate) are embedded in the alginate hydrogel matrix and subsequently act as crystallization reactors. Controlled evaporation of this composite material produces core-shell structured alginate-PVA hydrogels with drug nanocrystals (500-650 nm) embedded within the core. Adjustable loading of API nanocrystals up to 83% by weight is achieved with dissolution (of 80% of the drug) occurring in as little as 30 min. A quantitative model is also developed and experimentally validated that the drug release patterns of the fenofibrate nanocrystals can be modulated by controlling the thickness of the PVA shell and drug loading. Thus, these composite materials offer a "designer" drug delivery system. Overall, our approach enables a novel means of simultaneous controlled crystallization and formulation of hydrophobic drugs that circumvents energy intensive top-down processes in traditional manufacturing. PMID- 27249403 TI - A full Bayes before-after study accounting for temporal and spatial effects: Evaluating the safety impact of new signal installations. AB - Recently, important advances in road safety statistics have been brought about by methods able to address issues other than the choice of the best error structure for modeling crash data. In particular, accounting for spatial and temporal interdependence, i.e., the notion that the collision occurrence of a site or unit times depend on those of others, has become an important issue that needs further research. Overall, autoregressive models can be used for this purpose as they can specify that the output variable depends on its own previous values and on a stochastic term. Spatial effects have been investigated and applied mostly in the context of developing safety performance functions (SPFs) to relate crash occurrence to highway characteristics. Hence, there is a need for studies that attempt to estimate the effectiveness of safety countermeasures by including the spatial interdependence of road sites within the context of an observational before-after (BA) study. Moreover, the combination of temporal dynamics and spatial effects on crash frequency has not been explored in depth for SPF development. Therefore, the main goal of this research was to carry out a BA study accounting for spatial effects and temporal dynamics in evaluating the effectiveness of a road safety treatment. The countermeasure analyzed was the installation of traffic signals at unsignalized urban/suburban intersections in British Columbia (Canada). The full Bayes approach was selected as the statistical framework to develop the models. The results demonstrated that zone variation was a major component of total crash variability and that spatial effects were alleviated by clustering intersections together. Finally, the methodology used also allowed estimation of the treatment's effectiveness in the form of crash modification factors and functions with time trends. PMID- 27249413 TI - Correction: Therapist Effects and the Impact of Early Therapeutic Alliance on Symptomatic Outcome in Chronic Fatigue Syndrome. AB - [This corrects the article DOI: 10.1371/journal.pone.0144623.]. PMID- 27249414 TI - A Retrospective Analysis of Spontaneous Adverse Drug Reactions Reports Relating to Paediatric Patients. AB - BACKGROUND: Spontaneous reporting on adverse drug reactions (ADR) has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups. METHODS: Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification), category of ADR (according to system organ class) as well as the severity of the ADR. RESULTS: In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%). The most common ADRs reported were from the following system organ classes: application site disorders (32.2%), skin and appendages disorders (20.6%), body as a whole general disorders (12.8%) and central and peripheral nervous system disorders (11.2%). Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0%) were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%). Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities. DISCUSSION: ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of the ADRs manifesting in skin reactions. The majority of the ADR reports were received from nurses in the public sector, reporting ADRs associated with vaccine administration. The low fatality rate of ADR cases reported could potentially be caused by reporting bias due to the very low reporting percentage from the private healthcare institutions. This study indicates that ADR rates among Malaysian children are higher than in developed countries. Constant ADR reporting and monitoring, especially in respect to paediatric patients, should be undertaken to ensure their safety. PMID- 27249415 TI - Association between fractional exhaled nitric oxide (FeNO) cutoff values (25 ppb) and risk factors of cough. AB - INTRODUCTION: Cough is among the most common symptoms for patients to seek medical attention. OBJECTIVES: The purpose of this study is to evaluate the association between fractional exhaled nitric oxide (FeNO) cutoff values (25 ppb) and risk factors related to cough, hoping to evaluate the feasibility of the FeNO cut point values (25 ppb) for clinical prediction of cough in etiology. METHODS: In 107 adult patients with acute, subacute, or chronic cough, the FeNO, forced expiratory volume for 1 second (FEV1), forced vital capacity (FVC), blood routine (white blood cell and neutrophil), immunoglobulin E (IgE), lymphocyte eosinophils, and hemoglobin were measured. The Student's t-test was used to test the differences of FeNO levels compared with FEV1/FVC, lymphocyte, and hemoglobin level. For evaluating the correlation of FeNO levels with IgE, eosinophil, blood routine, pulmonary infection, and smoking status, the chi-square test was performed. RESULTS: FeNO cutoff value (25 ppb) significantly correlated with serum IgE (P < .0001) between >=200 IU/mL and <200 IU/mL level, eosinophil (P = .039) between >=5% and <5% level, lymphocyte percentage (P = .032) and the ratio of FEV1/FVC (P = .032), while weakly correlated with pulmonary infection, blood routine (white blood cell and neutrophil), hemoglobin, and smoking. CONCLUSION: The cutoff values of FeNO (>=25 ppb or <25 ppb) are useful for etiological detection of cough with high sensitivity. PMID- 27249416 TI - Serum Anion Gap Predicts All-Cause Mortality in Patients with Advanced Chronic Kidney Disease: A Retrospective Analysis of a Randomized Controlled Study. AB - BACKGROUND AND OBJECTIVES: Cardiovascular outcomes and mortality rates are poor in advanced chronic kidney disease (CKD) patients. Novel risk factors related to clinical outcomes should be identified. METHODS: A retrospective analysis of data from a randomized controlled study was performed in 440 CKD patients aged > 18 years, with estimated glomerular filtration rate 15-60 mL/min/1.73m2. Clinical data were available, and the albumin-adjusted serum anion gap (A-SAG) could be calculated. The outcome analyzed was all-cause mortality. RESULTS: Of 440 participants, the median (interquartile range, IQR) follow-up duration was 5.1 (3.0-5.5) years. During the follow-up duration, 29 participants died (all-cause mortality 6.6%). The area under the receiver operating characteristic curve of A SAG for all-cause mortality was 0.616 (95% CI 0.520-0.712, P = 0.037). The best threshold of A-SAG for all-cause mortality was 9.48 mmol/L, with sensitivity 0.793 and specificity 0.431. After adjusting for confounders, A-SAG above 9.48 mmol/L was independently associated with increased risk of all-cause mortality, with hazard ratio 2.968 (95% CI 1.143-7.708, P = 0.025). In our study, serum levels of beta-2 microglobulin and blood urea nitrogen (BUN) were positively associated with A-SAG. CONCLUSIONS: A-SAG is an independent risk factor for all cause mortality in advanced CKD patients. The positive correlation between A-SAG and serum beta-2 microglobulin or BUN might be a potential reason. Future study is needed. TRIAL REGISTRATION: Clinicaltrials.gov NCT 00860431. PMID- 27249417 TI - The Distribution of SIgA and IgG Antibody-Secreting Cells in the Small Intestine of Bactrian Camels (Camelus bactrianus) of Different Ages. AB - Secretory immunoglobulin A (SIgA) and immunoglobulin G (IgG) antibody-secreting cells (ASCs) are two important cell types in the mucosal immune system. This study aimed to explore the distribution of these ASC populations in the small intestine of Bactrian camels of different ages. Twenty-four Alashan Bactrian camels were divided into the following four age groups: young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). SIgA and IgG ASCs in the intestinal mucosa lamina propria (LP) were observed and analyzed using immunohistochemcal techniques. The results from all age groups show that both SIgA and IgG ASCs were diffusely distributed in the intestinal LP, and some cells aggregated around the crypts. Moreover, the densities of the two ASC populations gradually increased from the duodenum to the jejunum and then decreased in the ileum. Meanwhile, there were more SIgA ASCs than IgG ASCs in the duodenum, jejunum, and ileum, and these differences were significant in the young and pubertal groups (P<0.05). In addition, the SIgA and IgG ASC densities increased from the young to the pubertal period, peaked at puberty, and then gradually decreased with age. The results demonstrate that the SIgA and IgG ASC distributions help to form two immunoglobulin barriers in the intestinal mucosa to provide full protection, helping to maintain homeostasis. These findings also underscore the importance of researching the development and degeneration of intestinal mucosal immunity in Bactrian camels. PMID- 27249419 TI - A Systematic Review of Health Economic Analyses of Housing Improvement Interventions and Insecticide-Treated Bednets in the Home. AB - BACKGROUND: Housing improvements have considerable potential for improving health. So does the provision of insecticide-treated bednets for malaria prevention. Therefore we aimed to conduct updated systematic reviews of health economic analyses in both these intervention domains. METHODS AND FINDINGS: The search strategy included economic analyses of housing improvement interventions and use of insecticide-treated bednets for community-dwelling, healthy populations (published between 1 January 2000 and 15 April 2014). We searched the Cochrane Database of Systematic Reviews, MEDLINE, PubMed, EMBASE, and three health economics databases. Thirty-five economic analyses of seven types of intervention fulfilled the inclusion criteria. Most included studies adopted a health sector perspective and were cost-effectiveness analyses using decision analytic modeling or conducted alongside trials. The overall quality of the studies was generally likely to be adequate for informing policy-making (albeit with limitations in some areas). There was fairly consistent evidence for the cost-effectiveness/favorable cost-benefit of removing indoor lead to prevent lead poisoning and sequelae, and retrofitting insulation to prevent lung disease. But the value of assessing and improving home safety and providing smoke alarms to prevent injuries was more mixed and the economic evidence was inconclusive or insufficient for: home ventilation to prevent lung disease, installing heaters to prevent lung disease and regulating tap water temperatures to prevent scalding. Few studies (n = 4) considered health equity. The 12 studies of providing insecticide-treated bednets or hammocks to prevent malaria found these interventions to be moderately to highly cost-effective. CONCLUSIONS: This systematic review provides updated evidence that several housing improvement interventions (such as removing indoor lead and retrofitting insulation) and also the provision of insecticide-treated bednets are cost-effective interventions. Nevertheless, for some interventions additional analyses are required to better clarify their health economic and health equity value. PMID- 27249418 TI - DYT1 dystonia increases risk taking in humans. AB - It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a motor disorder caused by a single gene mutation, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans. PMID- 27249420 TI - Towards proactive active living: patients with Parkinson's disease experience of a multidisciplinary intensive rehabilitation treatment. AB - BACKGROUND: Non-pharmacological approaches to PD disease management seem to be a growing and promising field of investigation. Indeed interesting new perspectives are forthcoming from studies on physical rehabilitation and on physical exercise. AIM: To qualitatively describe the rehabilitation experience of Parkinson Disease patients taking part in a multidisciplinary intensive rehabilitation treatment (MIRT) consisting of four weeks of physical therapy and exercise, with three daily sessions, five days a week. DESIGN: Data from a qualitative observational study with patients' interviews were analyzed. SETTING: PD inpatients of a Neurorehabilitation Department. POPULATION: Convenient sample of 27 PD patients (13 male, 14 female), mean age 70.3+/-8.5 and mean disease duration 8.25+/-6.9 years; Hoehn-Yahr stage 3, hospitalized for the 4-week MIRT. METHODS: Verbatim transcriptions of 27 semi-structured interviews were analysed using the Grounded Theory methodology. RESULTS: Depressive symptoms were present in 55.5% of the patients measured by Geriatric Depression Scale: mild (N.=8; 30.0%), moderate (N.=6; 22.2%), severe (N.=1; 3.7%). The core category Efficacy of active living identified the becoming conscious of the usefulness of a proactive lifestyle to counterattack disease degeneration. The category Satisfaction described patients' satisfaction upon MIRT, resulting in a perceived enhanced functionality (coherently with quantitative functional parameters improvement at discharge) and a rediscovered autonomy. The category Future described the intention to continue the rehabilitation prescription at home embracing a more dynamic lifestyle. Of interest is that the majority in the interview used body related terms and described perceived changes through the body itself. Verbs of perception (to see, to feel, to perceive) were used in a spontaneous way by all inpatients. The inpatients experienced not only through their mind but also by means of body perceptions how a proactive lifestyle could become a means of disease control. CONCLUSIONS: The positive subjective response to rehabilitation described qualitatively in this study, opens perspectives for tailoring interventions focusing also on patients' self, self-efficacy and perceived efficacy of active living. CLINICAL REHABILITATION IMPACT: Patients' proactive disposition may widen the perspective on patients' motivation to rehabilitation. A multidisciplinary intervention may act both on physical and subjective disease aspects; paying attention to patients' subjective feedbacks could contribute reliably to guide for medical decisions in managing tailored and detailed interventions. PMID- 27249421 TI - Increase in Self-Injury as a Method of Self-Harm in Ghent, Belgium: 1987-2013. AB - BACKGROUND: Self-harm is a major health care problem and changes in its prevalence and characteristics can have important implications for suicide prevention. The objective was to describe trends in the epidemiology of self-harm based on emergency department (A&E departments) visits over a 26-year period in Ghent, Belgium. METHODS: We analyzed data on all self-harm presentations from the three large general hospitals in Ghent between 1987 and 2013. We investigated trends in prevalence (events by year per 100.000), methods and alcohol use. RESULTS: Rates of self-harm steadily decreased during the 26-year study period. In general female rates of self-harm were higher than male rates. The mean patient age was 35 years. The most commonly used method of self-harm was self poisoning by means of an overdose of medication (80.8%), followed by cutting (10.2%) and hanging (4.2%). Psychotropics (including antidepressants, benzodiazepines, barbiturates and other tranquilizers) were the most frequently used drugs (74.5%). A proportional increase in the use of self-injurious methods in self-harm was highly significant, more specifically in the use of hanging, jumping from heights and the use of other violent methods such as the use of firearms, jumping before a moving object or other traffic related injury. CONCLUSION: This epidemiological study showed an increase in the use of high lethality methods in self-harm which has important implications for suicide prevention. As restrictions in the availability of these methods are difficult or impossible to achieve, prevention programmes will have to emphasize the role of thorough psychosocial assessment and adequate follow-up care of self-harm patients. PMID- 27249422 TI - Topical treatment with a two-component gel releasing nitric oxide cures C57BL/6 mice from cutaneous leishmaniasis caused by Leishmania major. PMID- 27249425 TI - HTCC: Broad Range Inhibitor of Coronavirus Entry. AB - To date, six human coronaviruses have been known, all of which are associated with respiratory infections in humans. With the exception of the highly pathogenic SARS and MERS coronaviruses, human coronaviruses (HCoV-NL63, HCoV OC43, HCoV-229E, and HCoV-HKU1) circulate worldwide and typically cause the common cold. In most cases, infection with these viruses does not lead to severe disease, although acute infections in infants, the elderly, and immunocompromised patients may progress to severe disease requiring hospitalization. Importantly, no drugs against human coronaviruses exist, and only supportive therapy is available. Previously, we proposed the cationically modified chitosan, N-(2 hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and its hydrophobically-modified derivative (HM-HTCC) as potent inhibitors of the coronavirus HCoV-NL63. Here, we show that HTCC inhibits interaction of a virus with its receptor and thus blocks the entry. Further, we demonstrate that HTCC polymers with different degrees of substitution act as effective inhibitors of all low-pathogenic human coronaviruses. PMID- 27249426 TI - Misinterpretation in Nanotoxicology: A Personal Perspective. AB - As an emerging field, nanotoxicology is gaining significant interest from scientists as well as from international regulatory firms in an attempt to build accumulated knowledge on this topic, which will be the basis for regulatory codes and safer nanotechnology. However, conflicting results and findings are abundant in the literature calling for more careful experimental design, result interpretation, and detailed reporting. In this perspective, we focus on misinterpretation in nanotoxicology and highlight the importance of proper experimental practice to avoid artifacts by discussing various examples from the literature. PMID- 27249427 TI - HYPOGENESIS OF RIGHT LOBE OF LIVER ACCOMPANIED BY PORTAL HYPERTENSION AND ESOPHAGOGASTRIC VARICEAL BLEEDING; A RARE ANOMALY: A CASE REPORT. AB - Hypo-agenesis of the right lobe of the liver is an extremely rare finding. It is defined as the complete or partial absence of liver tissue on the right side without previous disease or surgery. It is usually an incidental finding. A 32 year-old female patient came to Emergency Department of TSMU the First University Clinic 22.10.2015 with an initial diagnosis of upper gastrointestinal bleeding. Her medical history showed no previous diseases of the liver or episodes of hemorrhage. Dizziness, nausea, vomiting with red blood, melena was presented on admission. Esophagogastroduodenoscopy revealed III degree varicose of veins from middle part of the esophagus to cardiofundal part of the stomach. Hemorrhage was observed from cardial part of the stomach. Control of bleeding was not achieved endoscopically. Sengstaken-Blakemore tube was used to stop bleeding temporarily. Computed tomography with angiography was performed. Right lobe of the liver was presented with VII and VIII segments. Medial edge of the left lobe of the liver is located near the spleen. Liver parenchyma is homogenous. No thrombosis of the portal or hepatic veins was revealed. Gallbladder was dislocated laterally and cranially without pathological changes. Extra- and intrahepatic biliary ducts were not dilated. There was colonic interposition between the liver and diaphragm. Diagnosis was established - hypogenesis of right lobe of liver, atrophy-hypertrophy complex, portal hypertension, varicose of the veins of the esophagus and cardiofundal part of the stomach, hemorrhage from variceal vein of the cardial part of the stomach, acquired coagulation factors deficiency, functional hypersplenism, posthemorrhagic anemia. In our case there was congenital hypogenesis of the right lobe of the liver. Five months follow-up showed no recurrent bleeding. PMID- 27249428 TI - [PROBLEMS OF NEWBORN NEONATAL ADAPTATION FROM A TWINS]. AB - The clinical analysis of multiple pregnancies. The features of neonatal adaptation process in 96 twins, depending on the type of zygosity. It is proved that the adaptation of the newborn with multiple pregnancy depends on the type of placentation. It is found that monozygotic twins is a risk factor syndromes disadaptation. Children from monozygotic twins compared with dizygotic twins have a higher frequency of the syndrome of respiratory disorders, and more prone to jaundice, hemorrhagic syndrome, violation gemolikvorodinamics II and III degrees. The physical development of the twins also determined by the type zygosity. In the group of monozygotic twins are more common heavier versions of intrauterine growth retardation - hypoplastic and dysplastic. The high frequency of asphyxia on the background of immaturity that leads to the development disadaptation syndromes in these children, the most common of which are hypoxic-ischemic CNS disorders, thermoregulation, jaundice and gastrointestinal reactions. Detection disorders of blood coagulation and glucose metabolism certainly play a negative role in the development of adaptation of these newborns. zygosity type must be determined at the time of pregnancy to produce medical tactics and prognosis. PMID- 27249429 TI - [SOME CLINICAL AND IMMUNOLOGICAL ASPECTS OF PRETERM BIRTH]. AB - Aim - to make a comparative assessment of the cytokines level in women with preterm labor with chronic infection and without it in order to determine the risk of implementation of intrauterine infection in their preterm infants. There was prospective investigation of 141 pregnant and their 141 premature infants with different gestation terms. There was identify cytokines levels in mother's blood with immune enzyme analysis method due implementation of intrauterine infection in compare with control group. It wasinterconnection ofinfection pathology withgestation terms, it lead to preterm labor. Prematurity which cause by mothers chronic infection, lead to heavier, extended period of bacterial infection in premature infants. It was increasing of cytokines levels IL-1beta, IL-6, and TNF-alpha of mother's blood during implementation of intrauterine infection in premature infants. Multiparous pregnant, adverse outcomes of previous pregnancies in anamnesis, high frequency carrier of bacterial infection were risk factors for preterm labor among explored pregnant women. To study cytokine profile among the explored pregnant women from main group showed a pattern in increasing of level IL-1beta, IL- 6 and TNF-alpha serum during pregnancy , indicating the course of pregnancy and can be used as a nonspecific marker for early diagnosis of preterm birth and implementing infection in premature . The level of IL-2 did not have a diagnostic value. PMID- 27249430 TI - THE USE OF 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY TO ASSESS CLINICAL OUTCOMES OF PATIENTS WITH BORDERLINE RESECTABLE PANCREATIC CANCER. AB - The aim of this study is to evaluate the effect of 18FDG PET on preoperative staging and clinical management of pancreatic cancer. Between December 2011 and February 2015, 28 consecutive patients with borderline resectable pancreatic cancer were evaluated with both 18FDG PET scans and conventional preoperative imaging studies. Medical records of all patients were noted prospectively. 18FDG PET findings were compared with conventional imaging studies and over-staging or down-staging rates with changes in clinical management were evaluated. The correlation of 18FDG PET with conventional imaging studies was evaluated with a kappa agreement coefficient. A number of 22 (78.5%) patients had pancreatic head cancer and 6 (21.4%) patients had pancreatic body and tail cancers. Based on 18FDG PET, additional lesions were found in 4 (14.28%) of the patients which were lung and peritoneal lesions as metastasis. No hepatic metastasis or supraclavicular lymph node involvement was confirmed in patients. Routine use of 18FDG PET for preoperative staging has not an effect on cancer management in 96.8% of our patients. In conclusion, 18FDG PET has additional value over conventional radiologic techniques for monitoring the treatment response in locally advanced pancreatic cancer patients. It is feasible to predict early metastasis and patient outcome early (after one course of IC) during therapy. PMID- 27249431 TI - EVALUATION OF EDENTULISM, PROSTHETIC STATUS AND PROSTHODONTICS TREATMENT NEEDS AMONG THE ADULT POPULATION OF GEORGIA. AB - The aim of the present study is to identify the level of edentulism among the adult population of Georgia, to assess the prosthodontics status and normative needs for prosthetic treatment. Cluster- stratified method was used for sampling. Overall, 2370 adults including 1289 women and 1081 men and four age groups I - 20 34, II - 35-44, III - 45-64, IV - 65-74 in nine regions of Georgia and the capital, Tbilisi, were examined. The loss of teeth due to caries or periodontitis was observed to differing extents throughout the population. One (8.3%) or more bridges (7.6%) and removable dentures (3.2-4.7%) were more frequently observed than implants (0.1%). Metal-ceramic (12.4%) and metal crowns (6.3%) were more commonly detected than zirconia ceramic crowns (0.1%). Statistical analysis of the data demonstrates a rather high normative prosthetic need of implants and bridges and less needs for removable dentures among the population due to less severity of periodontitis and not too high values of missing teeth due to caries (despite the high caries prevalence (99%) throughout the Georgian population). Edentulism is a public problem in Georgia and needs serious attention from government or healthcare centers to prevent the complications . PMID- 27249432 TI - THE RISK FACTORS INFLUENCING THE EDENTULISM AND PROSTHETIC STATUS OF THE ADULT POPULATION IN DIFFERENT REGIONS OF GEORGIA. AB - The aim of the present study was to identify the level of edentulism and prosthetic status of the adult population in different regions of Georgia and to assess the influencing risk- factors. Cluster- stratified method was used for sampling. Overall, 2370 adults including 1289 women and 1081 men and four age groups I- (20-34), II-(35-44), III-(45-64), IV- (65-74) in nine regions of Georgia and the capital, Tbilisi, were examined. Statistically reliable data received showed the different extent of teeth loss in various regions of Georgia. <=10 teeth loss were characteristic for Mtskheta (60.2%) and Samtskhe-Javakheti (50.7%),whilst >=20 teeth lost were noticed more in Achara(2.9%), Samtskhe Javakheti(2.6%), Shida Qartli (2,5%). Therefore, prosthetic status was mostly presented with one or more bridges or artificial crowns, removable dentures were seen less. Differences in prosthetic status is generally related to low medical education background in all regions, though lack of money was considered as essential obstacle for dental visit for Mtskheta, Imereti and Samtskhe-Javakheti population. Education and family income dictate attitudes towards prosthetic dental care and choice of crown types. On the other hand, material disparity represents the main obstacle to prosthetic procedures, especially implants. PMID- 27249433 TI - MONITORING THE EFFICACY OF MONTELUKAST USED IN CHILDREN WITH RISK OF ASTHMA. AB - The aim of the study is to evaluate the effect of Montelukast - leukotriene inhibitor in children population with risk of bronchial asthma. The research was conducted at LTD. Kutaisi Children primary care unit #3. The data were collected from January 2013 till January 2016. 104 patients (5-18 year, 43 girl, 61 boy), with potential risk of bronchial asthma were involved into the research, 47 (45%) patients out of 104 were considered as a real risk for asthma, based on Peak Expiratory Flow (PEF) and spirometry results. Patients with risk of asthma were grouped according to the method of treatment (monotherapy with inhaled glycocorticoid and inhaled glycocorticoid combined with leukotriene inhibitor). Descriptive statistics methods were used to characterize each variable. Our results indicate on positive influence of montelukast - selective leukotrien inhibitor in treatment of children with various forms of asthma. PMID- 27249434 TI - POSTNATAL GROWTH IN PRETERMS WITH BRONCHOPULMONARY DYSPLASIA. AB - Aim of study - to measure growth data for 69 preterms (39 females) with bronchopulmonary dysplasia (PT-BPD) The growth parameters of 69 BPD-PT were recorded for 16+/-3 months postnatally. 40 had mild, 20 had moderate and 9 had severe BPD. Ninety-six percent of infants were appropriate for gestational age (AGA). Only 4% preterms had birth weight SDS <-2 for gestational age (GA) and 4% had length SDS (LSDS) <-2. Eighty-eight percent of PT-BPD had normal or accelerated growth velocity (GV) during the 16+/-3 months period. At 8+/-2 months of uncorrected age 45% had LSDS <-2 and at 16+/-3 months of age 25% had LSDS <-2. At 8+/-2 months 13% had body mass index SDS (BMISDS) < -2 and at 16+/-3 months 5.8% had BMISDS < -2. At 8+/-2 months 52% had head circumference SDS (HCSDS2) < 2. At 16+/-3 months 27.5% had HCSDS <-2. Seventy-two per cent of PT-BPD had normal HCSDS compared to full terms (FT) infants at 16+/-3 months. The majority of preterm infants with BPD show normal or above normal (catch-up growth) linear growth velocity postnatally compared to FT infants. At 16+/-3 months of their life 75% had normal LSDS, 72.5% had normal HCSDS compared to FT infants. Severity of the BPD, and the presence of sepsis, NEC, PDA and PVH ominously affects postnatal somatic growth in these infants. Our results stress also the importance of corrected vs uncorrected age for the growth evaluation. PMID- 27249435 TI - [QUALITY OF LIFE IN CARERS OF PATIENTS WITH MULTIPLE SCLEROSIS TAKING A DISEASE MODIFYING MEDICATION: A PILOT STUDY]. AB - A chronic physical disease not only has direct consequences for the chronically ill person but can also distort the life of the healthy family member. The aim of our study was to measure the health-related quality of life (QOL) in people caring for patients with relapsing-remitting form of multiple sclerosis (MS) and currently treated with disease-modifying drugs. Eligible patients were selected via Sarajishvili Institute of Neurology database for MS. 25 carers (mean age 40.7; 56% women, 56% partners) and 25 sex and age-matched controls completed 36 item Short Form Health Survey (SF-36), version 2. Carers also completed the Beck depression Inventory (BDI-II). Compared to carers, patients were found to have a lower QOL (P<0.05 for five dimensions). However, no significant difference was observed in SF-36 domains scores between carers and controls except general health score which was lower in carers (63.3 vs 75.6, p=0.016). A strong negative correlation was found between BDI and all SF-36 dimension scores of carers. The association remains unchanged even adjusted to carers other independent variables. Last year relapse rate was the only clinical variable correlated with carers QOL dimensions. Our pilot study demonstrated that QOL in carers of patients with relapsing-remitting MS receiving disease-modifying treatment is minimally affected. Further study with large sample size is warranted. PMID- 27249436 TI - QTC TENDENCY IN PACEMAKER DEPENDENT PATIENTS - PROGNOSTIC MEANING OF LONG QTC DURING 5 YEAR FOLLOW UP. AB - Prolongation of ventricular repolarization, which is represented by QTc prolongation on the standard ECG can be considered as increased risk for fatal arrhythmia. However, in pacemaker dependency (with ventricular pacing from the right apex) Ventricular Pacemaker causes abnormal steps of ventricular activation and therefore widens QRS complex and alters ventricular repolarization. It is still questionable whether QTc prolongation in right ventricular-paced patients is associated with increased risk of fatal arrhythmia or other cardiac complications. The other important question is whether the pacemaker dependent patient with long QTc interval may safely receive medications with known potential to prolong ventricular repolarization. The aim of the study was to determine whether QTc prolongation in VP (ventricular pacemaker) patients is associated with increased risk of fatal arrhythmia or other cardiac complications and whether these patients can safely receive medications with known potential to prolong ventricular repolarization. The study is based on retrospective analysis of the QTc interval prior and after pacemaker insertion; dynamic changes of QTc interval and possible influence of the medications, with known potential to prolong ventricular repolarization. Study population consisted 76 patients with narrow native QRS complexes and QTcF/QTcB <500 ms for both male and female patients. QTc prolongation in VP patients most likely does not represent true repolarization abnormalities and is not associated with risk of fatal arrhythmia. While analysis of group receiving medications with known potency of QTc increase we found no additional tendency of QTc increase. Based on our data receiving the medications with known potency of QTc prolongation in VP patients should be considered as safe approach. Long-term follow up data (5 years) assessed retrospectively shows that in patients with widened QRS after VP are at increased risk of development of HF and HF decompensation. PMID- 27249437 TI - [THE FIRST RESULTS OF THE PREVALENCE OF CYP2C19 GENEPOLYMORPHISM IN PATIENTS WITH ACUTE CORONARY SYNDROME IN THE AKTYUBINSK POPULATION]. AB - To study the prevalence of polymorphic variants of CYP2C19 in residents of the Aktyubinsk region, in patients with acute coronary syndrome after percutaneous coronary intervention. We studied included 100 patients with documented acute coronary syndrome, whom stent has been implanted and double antiplatelet therapy (aspirin and clopidogrel) was administered (average age was 49.2). The control group was formed of 255 volunteers without clinical and electrocardiographic manifestations of ischemia, and cardiovascular disease (CVD). In groups of patients and volunteers, most of them were ethnic Kazakhs 67% and 72% respectively. Thus, about 30% of patients CYP2C19*1/*2 acute coronary syndrome who live in Aktobe (Aktobe residents) are under the threat of a possible occurrence of new cardiovascular events due to low sensitivity to clopidogrel. Our study confirms that CYP2C19 G (681A) genotype has impact on antiplatelet effect of clopidogrel. The peculiarity of our work lies in the fact that we were the first who conducted pharmacogenetic study in patients treated with clopidogrel with ACS/PCI in the region inhabited by persons of mixed Slavic and Kazakh nationality. PMID- 27249438 TI - [THE CONTENT OF SOME ESSENTIAL MICRONUTRIENTS IN INFANTS WITH LOW BIRTH WEIGHT WITH INTRAUTERINE HERPES INFECTION]. AB - To study the comparative aspect of the content of certain essential trace elements in the blood serum of infants with low birth weight, identify the clinical signs of deficiency. The study involved 127 infants, of which 69 constituted the main group and 58 infants constituted the comparison group. All newborns were identified haematological and biochemical blood tests, some Essential micronutrients (copper, selenium, zinc). Laboratory diagnosis of microelement composition of blood was determined by mass spectrometry with inductively coupled argon plasma (ICP-MS). The analysis of some essential trace elements was diagnosed copper and selenium deficiency in all newborns. Mean while neonatal treatment group indicators selenium, copper are lower, than similar nutrients infants in the control group. The zinc content in both groups mostly within the normal parameters. Thus, the level of essential micronutrients (copper, selenium) in the blood serum of newborn infants in the study group and the control group was below the reference value, indicating that insufficient intake data trace in the fetus located in the mother's womb. RECOMMENDATIONS: 1. In the diagnosis of various diseases in newborns with low birth weight should take into account the level of serum essential micronutrients (copper, selenium). 2. In the appointment of the underlying disease treatment in these infants need to be borne in mind also correct micronutrient deficiencies. PMID- 27249439 TI - SENSITIZATION PATTERN AND CLINICAL PECULARITIES OF FOOD ALLERGY IN GEORGIA. AB - The aim of our study was to investigate sensitization pattern to food allergens in different age groups of atopic patients in Georgia and reveal the associations between food sensitization and clinical manifestations of allergic disease reflecting the development of atopic march. 1000 patients (children-783, adult 217) with different clinical manifestations were involved in the study. Specific IgE antibodies to food mix, cow's milk, casein, egg, wheat, fish, nuts mixture and inhalant allergens were measured by using ImmunoCap (Phadia, Uppsala, Sweden). The prevalence of positive specific IgE to food mix was - 7.08%, cow's milk-4.61%, casein - 4.68%, hen's egg - 2.72%, fish mix - 0.77%, wheat -1.57% and to nuts mixture - 2.86%. The frequency of atopic dermatitis (p<0.0017), urticaria (p<0.0223) and anaphylactic shock (p<0.001) were significantly increased in patients with specific IgE to food mix. Allergic skin manifestations to ingested food were age-dependent, more frequent in children groups. Cow's milk and hen's egg are the commonest food allergens in the age group of <2 years. Sensitization to food mix, cow's milk, casein, hen's egg and wheat were predominated in male patients. Egg allergy was significantly associated with atopic dermatitis, fish allergy to bronchial asthma and severe milk allergy to anaphylactic shock. Present study is a first comprehensive investigation, providing unique data of the prevalence of food allergies in Georgian population. The results of this study are contributing to a better understanding of the disease, serving as a basis for the development of strategies for preventing and treating food allergies. PMID- 27249440 TI - [BREATH TEST WITH LOCALLY PRODUCED 13S-UREA (TBILISI, GEORGIA) IN DIAGNOSTICS OF HELICOBACTER PYLORI INFECTION]. AB - Comparative assessment of results of detection of Helicobacter pylori (Hp) infection by breath tests with standard and locally produced 13S urea was done in 213 patients with gastric and duodenal pathology, including those who already were undergone the surgery. Invasive endoscopic biopsy test including rapid urease test (RUT), smear cytology and histology were also performed (tissue samples were obtained after endoscopy or surgery). RUT was carried out with the help of URE-HP test kit. Serological test for Hp antibodies was performed by IFA using kit ELISA. 13S urea breath test (UBT) was conducted for the determination of 13/12CO2 in breath samples by using of infrared spectroscope. In I group (125 patients) UBT was performed with standard 13S urea, in II group (88 patients) with locally produced 13S urea. Based on 5 different methods of Hp infection testing Hp positivity in 172 (80,8%) and Hp negativity in 41 (19,2%) patients were revealed. 13S-UBT showed the highest diagnostic value (accuracy-97,5%, sensibility-97,0%, specificity-100%) in Hp infection diagnosis. The (accuracy, sensibility and specificity of breath test with locally issued 13S urea (98,7%, 98,5% and 100% respectively) are the same as those for BT with standard 13S urea (96,7%, 96,2% and 100% respectively). These parameters are also highly credible in control of treatment efficiency (96,7%, 90,0% and 100% respectively). The correlation of index DOB0/00 of breath test with results of RUT was revealed In Hp positive patients. This can serve as a marker of Hp infection rate. Preliminarily, in pre-clinical experimental study, harmless of locally issued 13S urea from point of view of acute/sub-acute toxicity and allergy development was confirmed. The advantages (noninvasiveness, simplicity, rapidity, safety) and high diagnostic value of UBT (with both standard as well as locally produced 13S urea) provide the opportunity to offer 13S-UBT as screening method of Hp infection diagnosis. It also should be recommended as a method of choice for controlling of Hp treatment efficiency. Taking into the consideration all above mentioned we may recommend locally produced 13S-urea (Tbilisi, Georgia) for certification and further application. PMID- 27249441 TI - PRE-HOSPITAL EMERGENCY MEDICAL SERVICES FOR ELDERLY POPULATION IN TBILISI. AB - The importance of the issue is determined by the current demographic situation in Georgia and the world in general. The trend of growing the number of older people and the increase of the life span is obvious. At the same time in the number of countries, particularly in the developed western countries and Japan, the decrease of birth rate is noticed. Similar processes are taking place in Georgia; this logically increases the number of sick and weakened people, which means that taking care of them becomes more acute problem. Therefore, the purpose of this paper was the study of the situation of the pre-hospital emergency medical services in the Georgian capital Tbilisi during the period of 2012-2014. For this reason, the data provided by the Tbilisi Emergency Medical Service were used. Besides, we have also looked for the statistics of the different countries, including the US, Japan and South-East Asian countries. Attention was paid to the recommendations proposed because of the Monitoring of the European Union Mission in Georgia, which focuses on the social and economic protection of elderly. The tables and diagrams, describing the current conditions are provided. Since 2012, there has been launched the state health care program for the elderly in Georgia, but based on research conducted, it does not cover home care services while, the majority of the elderly are chronically sick people and suffer from the number of diseases. Results of the study can be used for improving quality of the Emergency Medical Service model in Georgia and finding the possible ways for its reforms. PMID- 27249442 TI - PREDICTORS OF POST-TRAUMATIC STRESS DISORDER IN MILITARY PERSONNEL DEPLOYED TO PEACEKEEPING MISSIONS. AB - As the empirical evidence suggests PTSD, depression and anxiety represent prevalent and severe problem in armed forces. High co morbidity of these disorders with each other further complicates clinical picture. Georgian military personnel regularly take part in different peacekeeping missions, however there is no existing data regarding associations of mental health problems in Georgian armed forces. Data was collected between 2014 and 2015, after 6 month deployment. Participants were 2810 Georgian military personnel who took part in peacekeeping missions. All participants were male, average age: M=31,2 (SD=6,3). All instruments used in the study were self-report scales. PTSD was measured by PCL 5; Depression and anxiety was measured by PHQ (Patient Health Questionnaire). Both variables - Severity of Anxiety symptoms and severity of depression symptoms independently predicted PTSD, but after being placed together in the same regression model, only depression symptom severity accounted for significant portion of variance. Due to the fact that the participants of our study (n=69) were young (M=29,68 ; SD=5,8) male personnel, our findings cannot be generalized. Also it should be considered, that for PTSD screening we used self-report questionnaires, which reduces liability of participants' answers and increases the tendency of self-biased responses. It is advisable for clinical practitioners and therapists to consider depression symptoms in patients with PTSD and screen for depression additionally, in order to exclude or include co morbidity factors in treatment course. PMID- 27249443 TI - [KINETICS OF PHOTO-INDUCED FREE RADICALS IN THE HUMAN HAIR CHESTNUT COLOR AFTER SHORT PERIODS OF RED, GREEN, BLUE AND WHITE LIGHT EXPOSURE]. AB - The aim of the study was to investigate the kinetics of photo-induced free radicals in the human hair chestnut color with short-term exposure to visible light in different frequency ranges. Studies carried out on human volunteers aged 17-21 years (n=37). Hairs of volunteers of the study were not treated with dyes and other active cosmetic preparations. Hairs bundled in a bun had a length - 1.5 cm, weight - 40 mg. At the beginning background EPR-spectrum of a sample was measured and then hairs were irradiated with visible light (blue, green, red and white) of different wavelength subsequently; exposure duration - 60 minutes; after the exposure the kinetics of photo-induced free radicals was measured within 60 minutes. The radiation source was selected LED array of the four crystals that provides a nearly monochromatic radiation spectrum having no parasitic infrared and ultraviolet radiations. The studies give a reason to assume that the impact on hairs by visible electromagnetic rays a leading factor is their frequency characteristics: on the one hand - the proximity of the blue light to ultraviolet radiation, and on the other - the red light to the infrared range. PMID- 27249444 TI - THE DETERMINATION OF CORRELATION LINKAGES BETWEEN LEVEL OF REACTIVE OXYGEN SPECIES, CONTENTS OF NEUTROPHILES AND BLOOD GAS COMPOSITION IN EXPERIMENTAL ACUTE LUNG INJURY. AB - Acute lung injury (ALI) remains a major cause of acute respiratory failure and death of patients. Despite the achievements at the current stage in treatment, morbidity and mortality of ALI remain high. However, a deeper understanding of the pathogenetic links of ALI, identifying of the predictors that positively or negatively influence on the course of the syndrome, the correlation between some pathogenetic mechanisms will improve therapeutic strategies for patients with ALI, which makes the actuality of this study. The aim of the research was to detect additional pathogenetic mechanisms of the acute lung injury development in rats based on a comparative analysis of the correlations between the level of reactive oxygen species in blood and bronchoalveolar lavage, contents of neutrophils and blood gas composition. The experiments were performed on 54 white nonlinear mature male rats 200-220g in weight. The animals were divided into 5 groups: the 1st - control group (n=6), the 2nd - animals affected by hydrochloric acid for 2 hours (n=12), the 3rd - animals affected by hydrochloric acid for 6 hours (n=12), the 4th - animals affected by hydrochloric acid for 12 hours (n=12), the 5th - animals affected by hydrochloric acid for 24 hours (n=12). Correlation analysis was performed between all the studied indices. Coefficient of linear correlation (r) and its fidelity (p) was calculated that was accordingly denoted in the tables (correlation matrices). The correlation coefficient was significant at p<0.05. Conducted correlative analysis showed that the level of ROS in neutrophils of blood in rats with modeled ALI had a high negative correlative linkage with pH of arterial blood in 2nd and 3rd experimental groups. Conducted correlative analysis of data in BAL showed that the level of ROS in neutrophils in rats with modeled ALI had a strong positive correlative relationship with the number of white blood cells in 3-rd, 4-th and 5 th experimental groups and positive correlative relationship with the absolute number of neutrophils in the same experimental group. Consequently, the main manifestation of acute lung injury is the development of hypoxia and respiratory acidosis that is caused by the violation of gases diffusion in the alveoli. On this background non-specific inflammatory reaction is developed at lung microvessels level with violation of lung homeostasis, which is iniciated by neutrophils' activation, which are producing ROS. PMID- 27249445 TI - [VEGETATIVE REGULATORY MECHANISMS IN DIFFERENT GEOMAGNETIC CONDITIONS DEPENDING ON A DEGREE OF PHYSICAL CONDITIONING]. AB - The aim of the study was to evaluate the vegetative regulatory action in healthy, untrained and trained individuals in different geomagnetic conditions. The study involved 94 healthy untrained young men aged 18-22 years - I group (control), and 60 trained volunteers aged 18-25 years - II group, who during the period of the study and for at least three years prior have been following active regular physical exercise regimen(weight lifting), but were not professional athletes. In order to evaluate the heart rate variability the following statistical indicators were studied: arithmetic mean, the arithmetic mean of the error variance, dispersion, the arithmetic mean deviation, coefficient of skewness, kurtosis, standard deviation of the mean. Geometric analysis was performed using a variation pulsometry. All the individuals were studied in natural/tranquil conditions, during naturally occuring or a simulated geomagnetic storm, which provided the use of the characteristics of vegetative balance as a marker for differential assessment of the impact of electromagnetic field (EMF). The forecast of natural geomagnetic conditions had been made at least three days before the study. Under the conditions of simulated geomagnetic storm the test subjects were placed in a solenoid with non-magnetic equipment. EMF inductance in the solenoid corresponded to the geomagnetic storm frequencies. The study had a nature of social experiment and was carried out by a single blind method: tested subjects were unaware of geomagnetic conditions during the study. This was an open, three-step, cohort, prospective study with parallel character. The results showed that under the uniform qualitative conditions (balanced, in particular) of initial state of vegetative equilibrium, the level of fitness of the human body determines the differentiated response to EMF exposure. Thus, with the possible inclusion of the EMF in the complex of therapeutic or preventive measures, it is necessary to predict homeostatic resources and body's reactivity to EMF exposure. PMID- 27249446 TI - PECULIARITIES OF THE CEREBELLUM NUCLEI IN AGED PERSONS. AB - The study of the clinical anatomy and functional features of the cortex, subcortical and conductive pathways of the cerebellum is necessary for clinicians for elaboration rational surgical approaches to these formations, for determination the localization of pathological processes associated with these formations. Cerebellar nucleus neurons are crucial to the olivo-cerebellar circuit as they provide the sole output of the entire cerebellum. The relationship between mobility and cognition in aging is well established, but the relationship between mobility and the structure and function of the aging brain is relatively unknown. In connection with the above, the purpose of our study was detection of the morphological characteristics of the cerebellum nuclei in aged persons. Study was performed on 48 specimens of the cerebellum from people (24 male and 24 female), who died at the age from 75 to 99 years due to diseases, which were not related to the central nervous system damaging. Formalin-fixed human hemispheres were dissected with the Ludwig and Klingler fiber dissection technique under x6 to x40 magnifications of binocular microscope Olympus BX41 (Japan). The morphological features of the human cerebellar nuclei were established. Namely, on the series of sections of the cerebellum in the horizontal, frontal and sagittal planes, as well as on the macro-microscopic preparations of the cerebellar nuclei location, their relative position, shape, linear dimensions, weight and volume were described. The features of macro microscopic and histological structure of the nuclei of the cerebellum were made own classification of the gyri and teeth of the dentate nucleus of the cerebellum was offered. Macro-microscopic dissection of persons died after 75 years old show no significant variability of linear dimensions of cerebellar nuclei with their specific location and options. Simultaneously, reliable reducing of cellular density was detected for Purkinje, granule and basket neurons more pronounced in male for Purkinje cells. PMID- 27249447 TI - MORPHOLOGICAL CHANGES OF RAT PLACENTA IN DIFFERENT PERIODS OF PREGNANCY UNDER MODELED PREECLAMPSIA. AB - The purpose of the study was to determine the morphological changes of rat placenta in II, III week of pregnancy under modeled preeclampsia. Modeling of preeclampsia was performed in the rats, as follows: lumen of the abdominal aorta below the renal artery was narrowed by the silk tread on the third of its diameter (0.2 mm). The placenta tissue was studied by histological and immunohistochemical methods (AE1/AE3, CD133, Ki-67). The study has shown that in the experimental model of preeclampsia at the end of II, III week of pregnancy the number of glycogen cells in the placenta trophyspongium layer is reduced compared with the control. There was shown sharp dilatation of the blood sinuses and lacuna, sometimes along the events of stasis. The volume of nucleated erythrocytes in fetal capillaries of the labyrinth layer is reduced compared with the control, especially in IIIweek of pregnancy. In the preparations marked by the CD133 marker, unlike to the norm of III week of pregnancy, the visualization of positive endothelial cells is complicated. The study of the preparations marked by Ki-67 marker reveals that the proliferated activity in the hypoxic placenta tissue is sharply reduced. The exception is those blood tubes, to which umbilical blood vessels are finally formed. It can be concluded that due to hypoxia placenta proliferation of placental blood vessels is disturbed that contributes to the disorder of placental blood circulation, reduce its metabolism in complications of pregnancy. PMID- 27249448 TI - The experience of regaining weight following weight loss surgery: A narrative phenomenological exploration. AB - Weight loss surgery (WLS) is gaining ground as the most effective treatment against obesity. In the literature, however, we see a divide among individuals who have undergone WLS based on the amount of weight lost and maintained: successful and unsuccessful patients. In this article, we focus on the notion of unsuccessful patients-exploring the accounts of three women who have regained weight following WLS. In doing so, we endeavor to better understand how weight regain has meaning, and its impact and implications for the lives of individuals who undergo WLS. The findings reveal how weight-regain stories are easily silenced, buried beneath social, cultural, and institutional/medical narratives of successful weight loss and transformation. People who have such experiences may feel reticent to reveal them and in doing so increase their own suffering, therefore leaving the popular narratives unchallenged. PMID- 27249449 TI - Timing of population peaks of Norway lemming in relation to atmospheric pressure: A hypothesis to explain the spatial synchrony. AB - Herbivore cycles are often synchronized over larger areas than what could be explained by dispersal. In Norway, the 3-4 year lemming cycle usually show no more than a one-year time lag between different regions, despite distances of up to 1000 km. If important food plants are forced to reallocate defensive proteins in years with high seed production, spatially synchronized herbivore outbreaks may be due to climate-synchronized peaks in flowering. Because lemming peaks are expected to occur one year after a flowering peak, and the formation of flower buds is induced in the year before flowering, a two-year time lag between flower inducing climate events and lemming peaks is predicted. At Hardangervidda, South Norway, the probability that a year was a population peak year of lemming during 1920-2014 increased with increasing midsummer atmospheric pressure two years earlier, even when the number of years since the previous peak was accounted for. PMID- 27249450 TI - The influence of atmospheric particles on the elemental content of vegetables in urban gardens of Sao Paulo, Brazil. AB - Although urban horticulture provides multiple benefits to society, the extent to which these vegetables are contaminated by the absorption of chemical elements derived from atmospheric deposition is unclear. This study was designed to evaluate the influence of air pollution on leafy vegetables in community gardens of Sao Paulo, Brazil. Vegetable seedlings of Brassica oleracea var. acephala (collard greens) and Spinacia oleracea (spinach) obtained in a non-polluted rural area and growing in vessels containing standard uncontaminated soil were exposed for three consecutive periods of 30, 60 and 90 days in 10 community gardens in Sao Paulo and in one control site. The concentrations of 17 chemical elements (traffic-related elements and those essential to plant biology) were quantified by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Tillandsia usneoides L. specimens were used as air plant biomonitors. The concentrations of As, Cd, Cr and Pb found in vegetables were compared to the recommended values for consumption. Principal Component Analysis (PCA) was used to cluster the elemental concentrations, and Generalized Linear Models (GLMs) were employed to evaluate the association of the factor scores from each PCA component with variables such as local weather, traffic burden and vertical barriers adjacent to the gardens. We found significant differences in the elemental concentrations of the vegetables in the different community gardens. These differences were related to the overall traffic burden, vertical obstacles and local weather. The Pb and Cd concentrations in both vegetables exceeded the limit values for consumption after 60 days of exposure. A strong correlation was observed between the concentration of traffic-related elements in vegetables and in Tillandsia usneoides L. An exposure response was observed between traffic burden and traffic-derived particles absorbed in the vegetables. Traffic-derived air pollution directly influences the absorption of chemical elements in leafy vegetables, and the levels of these elements may exceed the recommended values for consumption. PMID- 27249461 TI - A prospective, split-face, double-blinded, randomized study of the efficacy and safety of a fractional 1064-nm Q-switched Nd:YAG laser for photoaging-associated mottled pigmentation in Asian skin. AB - BACKGROUND: Laser toning using low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum laser (QSNY) has gained popularity in the treatment of photoaging-associated mottled pigmentation (PMP). However, hypopigmentation or lack of efficacy has been reported depending on the fluences used. OBJECTIVE: To compare a novel fractional 1064-nm QSNY with conventional 1064-nm QSNY for the treatment of photoaging-associated mottled pigmentary lesions except epidermal lesions of lentigines and freckles through a randomized, split-face, double-blind study. MATERIALS AND METHODS: Thirteen Asian women were treated every week for 6 weeks with fractional 1064-nm QSNY on one side of the face and conventional 1064 nm QSNY on the other side. We evaluated the pigmentation area and severity index (PSI), melanin index, erythema index, and the patient's global assessment of improvement. RESULTS: At three months post-treatment, the PSI score improved compared with baseline, by 14.48% on the conventional 1064-nm QSNY side and 21.81% on the fractional 1064-nm QSNY side. Both groups showed improvements in the melanin index. CONCLUSION: Both fractional 1064-nm QSNY and strictly low fluence conventional 1064-nm QSNY are moderately effective against PMP and other photoaging signs. Fractional laser toning shows better subjective outcomes than conventional toning. PMID- 27249513 TI - Validation of the Family Meeting Behavioral Skills Checklist. An Instrument to Assess Fellows' Communication Skills. AB - RATIONALE: Fellows in pulmonary and critical care medicine are required to show competency in facilitating family meetings for critically ill patients. There are many assessment measures available for evaluating physician-patient communication (e.g., the SEGUE Framework [Set the stage, Elicit information, Give information, Understand the patient's perspective, End the encounter]) and some designed for family meetings. However, no validated measure exists that is specifically designed to assess communication skills during family meetings with surrogate decision makers in intensive care settings. OBJECTIVES: We developed the Family Meeting Behavioral Skills Checklist (FMBSC) to measure advanced communication skills of fellows in family meetings of critically ill patients based on a literature review and consensus of an interdisciplinary group of communications experts. We evaluated the psychometric properties of the FMBSC. METHODS: We digitally recorded 16 pulmonary/critical care fellows performing a simulated family meeting for a critically ill patient at the end of 1 year of fellowship training. Two clinical health psychologists evaluated each recording independently using the FMBSC Rating Scale and the SEGUE Framework. Judges recorded the number of skills performed using the checklist and employed a summary rating scale to judge the level of performance for each of nine subsets of skills. Each instrument was scored and converted to percentage scores. The FMBSC and SEGUE Framework items were summed and converted to percentage scores for each category and as a total for each instrument. The rating scale items on the FMBSC were also summed and converted to a percentage score. Four primary analyses were conducted to evaluate interjudge reliability, internal consistency, and concurrent validity. MEASUREMENTS AND MAIN RESULTS: Interrater reliability was higher for the FMBSC (intraclass correlation [ICC2,2] = 0.57) than for the SEGUE instrument (ICC2,2 = 0.32) or the FMBSC Rating Scale (ICC2,2 = 0.23). The FMBSC demonstrated evidence of concurrent validity through high positive correlations with both the FMBSC Rating Scale and the SEGUE instrument (r = +0.83, P <= 0.01; r = +0.65, P <= 0.01 respectively). All but one of the nine subscales on the FMBSC showed adequate internal consistency (reliabilities ranged from 0.18 to 0.68). Interjudge reliability was higher for the FMBSC (ICC2,2 = 0.57) than for the SEGUE instrument (ICC2,2 = 0.32) or the FMBSC Rating Scale (ICC2,2 = 0.23). CONCLUSIONS: The FMBSC demonstrated internal consistency and structural validity in assessing advanced communication skills of fellows in facilitating family meetings of critically ill patients in the ICU. Interjudge reliability was better for the FMBS Checklist than it was for the other measures. PMID- 27249514 TI - Heterologous expression and purification of neurotoxic Hainantoxin-III in E. coli. AB - In the present study, we used Escherichia coli to produce recombinant Hainantoxin III (rHNTX-III), a 33-amino acid peptic toxin from the tarantula spider Haplopelma hainanum. The toxin has three pairs of disulfide bonds. A pET-HS-HNTX III vector was constructed and transformed into the E. coli strain SHuffleTM. rHNTX-III was expressed using auto-induction medium. After using a Ni-NTA column, the expressed fusion protein was digested using SUMO protease (ULP1) to remove the HIS-SUMO tag, and then RP-HPLC and ultrafiltration were used for further purification. Then the rHNTX-III was identified by MALDI-TOF/TOF mass spectrometry. The purified rHNTX-III was further analyzed using a whole-cell patch-clamp assay. It was shown that the rHNTX-III was able to block currents generated by human Nav1.7 (hNav1.7) at an IC50 of 225 nM and also have high selectivity for different voltage-gated sodium channels. Therefore, it has very similar activity to the natural one. PMID- 27249515 TI - Evidence for extensive pleiotropy among pharmacogenes. AB - AIM: We sought to identify potential pleiotropy involving pharmacogenes. METHODS: We tested 184 functional variants in 34 pharmacogenes for associations using a custom grouping of International Classification and Disease, Ninth Revision billing codes extracted from deidentified electronic health records of 6892 patients. RESULTS: We replicated several associations including ABCG2 (rs2231142) and gout (p = 1.73 * 10(-7); odds ratio [OR]: 1.73; 95% CI: 1.40-2.12); and SLCO1B1 (rs4149056) and jaundice (p = 2.50 * 10(-4); OR: 1.67; 95% CI: 1.27 2.20). CONCLUSION: In this systematic screen for phenotypic associations with functional variants, several novel genotype-phenotype combinations also achieved phenome-wide significance, including SLC15A2 rs1143672 and renal osteodystrophy (p = 2.67 * 10(-) (6); OR: 0.61; 95% CI: 0.49-0.75). PMID- 27249517 TI - Electrostatic Interactions Are Key to C?O n-pi* Shifts: An Experimental Proof. AB - Carbonyl n-pi* transitions are known to undergo blue shift in polar and hydrogen bonding solvents. Using semiempirical expressions, previous studies hypothesized several factors like change in dipole moment and hydrogen-bond strength upon excitation to cause the blue shift. Theoretically, ground-state electrostatics has been predicted to be the key to the observed shifts, however, an experimental proof has been lacking. Our experimental results demonstrate a consistent linear correlation between IR (ground-state phenomenon) and n-pi* frequency shifts (involves both ground and excited electronic-states) of carbonyls in hydrogen bonded and non-hydrogen-bonded environments. The carbonyl hydrogen-bonding status is experimentally verified from deviation in n-pi*/fluorescence correlation. The IR/n-pi* correlation validates the key role of electrostatic stabilization of the ground state toward n-pi* shifts and demonstrates the electrostatic nature of carbonyl hydrogen bonds. n-pi* shifts show linear sensitivity to calculated electrostatic fields on carbonyls. Our results portray the potential for n-pi* absorption to estimate local polarity in biomolecules and to probe chemical reactions involving carbonyl activation/stabilization. PMID- 27249518 TI - Epigenetic biomarkers in rheumatology - the future? AB - Epigenetic changes are stable modifications of DNA or histones that profoundly alter gene expression. They can be changed by environmental influences and can then be passed on to daughter cells or via the germ line to offspring. A variety of changes in epigenetic marks and in the expression of noncoding RNA has been found in cancer as well as in chronic inflammatory diseases. Interestingly, in both diseases similar mechanisms and pathways are affected albeit often to a different extent. DNA methylation is often lost in repetitive sequences, while in promoter regions hypo- as well as hypermethylation is found. Changes in microRNA levels typically affect microRNAs that are changed by an inflammatory environment, but disease specific changes have also been found in the blood and various cell types of patients with rheumatoid arthritis, systemic lupus erythematosus and other rheumatic diseases. Therefore, changes in the expression of microRNA in particular, but also demethylated gene loci, have been proposed as potential biomarkers in chronic inflammatory diseases and in cancer. Potentially, these changes could be used for early diagnosis and also to predict treatment response. Unfortunately most studies in rheumatology up to now were not designed to validate these epigenetic changes as biomarkers. Since the cancer field is much more advanced in the usage of biomarkers for disease subclassifications and subsequent therapeutic decisions, it is worthwhile to take a closer look at the biomarkers, methods and procedures used in oncology and to see which of these could also be applied to predicting disease severity and therapeutic response in rheumatic diseases. This article will highlight common epigenetic pathways activated in cancer and various rheumatic diseases and summarise epigenetic changes that have the potential to become biomarkers in rheumatic diseases. PMID- 27249516 TI - Unraveling the mechanisms of chromatin fibril packaging. AB - Recent data indicate that eukaryotic chromosomes are organized into Topologically Associating Domains (TADs); however, the mechanisms underlying TAD formation remain obscure. Based on the results of Hi-C analysis performed on 4 Drosophila melanogaster cell lines, we have proposed that specific properties of nucleosomes in active and repressed chromatin play a key role in the formation of TADs. Our computer simulations showed that the ability of "inactive" nucleosomes to stick to each other and the lack of such ability in "active" nucleosomes is sufficient for spatial segregation of these types of chromatin, which is revealed in the Hi C analysis as TAD/inter-TAD partitioning. However, some Drosophila and mammalian TADs contain both active and inactive chromatin, a fact that does not fit this model. Herein, we present additional arguments for the model by postulating that transcriptionally active chromatin is extruded on the surface of a TAD, and discuss the possible impact of this organization on the enhancer-promoter communication and on the segregation of TADs. PMID- 27249519 TI - Characterization of Staphylococcus aureus from Human Immunodeficiency Virus (HIV) patients in Accra, Ghana. AB - INTRODUCTION: The aims of this study were to: a) determine the nasal carriage prevalence of Stahpylococcus aureus among HIV patients, b) to characterize S. aureus strains isolated. METHODOLOGY: Characterization of S. aureus isolates was done by antibiotyping, spa typing, and detection of Panton-Valentine leukocidin (PVL) genes. RESULTS: S. aureus isolated (10/124; 8%) belonged to spa types t084 (n = 3), t10828 (n = 2), t311, t304, t774, t645, and t091. The isolates were resistant to penicillin (100%), tetracycline (40%), rifampicin (10%), fucidic acid (10%), norfloxacin (10%), erythromycin (10%), and sulfamethoxazole trimethoprim (10%). Multidrug resistance (MDR) was detected in 30% of the isolates. CONCLUSION: The finding of MDR S. aureus among HIV-positive patients suggests that surveillance of antimicrobial resistant S. aureus among this patient group could be considered as an infection control measure in the hospital. PMID- 27249520 TI - Lack of strong association of Chlamydia pneumoniae and atherosclerosis in a Jordanian population. AB - INTRODUCTION: The correlation of Chlamydia pneumoniae to coronary artery disease (CAD) in Jordan was investigated in this study. METHODOLOGY: Totals of 361 atherosclerotic patients and 392 apparently healthy controls of both sexes were enrolled. C. pneumoniae-specific IgG antibodies were measured by the microimmunofluorescence assay (MIF). The presence of the bacterial DNA in the blood by polymerase chain reaction (PCR) was also tested. RESULTS: The overall IgG seroprevalence, estimated at a titer of 1/16, was insignificantly higher in patients (75.9%) than in controls (71.7%). About 59.3% of patients demonstrated seropositivity at titers <= 1/256, which are suggestive of chronic or presumed past infection, whereas 54.1% of controls were seropositive at these titers (p > 0.05). Analysis of gender-specific seroprevalences revealed no obvious relation between C. pneumoniae and atherosclerosis in males (78.9% and 77.9% in atherosclerotic and control males, respectively; p > 0.05). However, a significantly elevated seropositivity was detected in atherosclerotic females (71.7%) compared with control females (64.2%). On the other hand, the PCR-based detection of C. pneumoniae DNA failed to correlate the bacterium to atherosclerosis. CONCLUSIONS: We were unable to show a strong association between C. pneumoniae and CAD, potentially because of the presence of high seroprevalence of C. pneumoniae antibodies and the unreliability of the whole blood-based nested PCR technique used. PMID- 27249521 TI - Methicillin-resistant S. aureus colonization in intensive care unit patients: Early identification and molecular typing. AB - INTRODUCTION: Early detection of methicillin-resistant Staphylococcus aureus (MRSA) in colonized patients is very important for infection control procedures to prevent MRSA spread. We aimed to monitor MRSA carriage in intensive care unit (ICU) patients and to evaluate the speed and efficiency of conventional culture, immunological, chromogenic, and molecular methods together with genotyping. METHODOLOGY: Nasal and axillar swab specimens were obtained from patients in the ICUs of the general surgery and neurosurgery wards in a tertiary hospital once a week over four weeks between December 2009 and July 2010. Oxacillin and cefoxitin disk diffusion tests, oxacillin agar screening test, latex agglutination test, chromogenic agar, and real-time polymerase chain reaction (PCR) tests were used for isolation and identification of MRSA. MRSA isolates were typed using ribotyping and pulsed-field gel electrophoresis (PFGE) typing. RESULTS: MRSA colonization was detected in 48 of 306 patients by real-time PCR. The MRSA colonization rate was 6.2%, 15.5%, and 38.5% at admission and in the first and second weeks, respectively. Sensitivity, specificity, positive and negative predictive values for all phenotypic tests were 98%, 99.6%, 98%, and 99.6%, respectively. The shortest handle time was observed in PCR. A total of three banding patterns were obtained from MRSA isolates by ribotyping, and PFGE analyses revealed 17 different pulsotypes varying from 11 to 18 distinct bands, showing high genetic diversity among the samples. CONCLUSION: Phenotypic MRSA screening tests in our study exhibited similar performances. The superiority of real-time PCR is its short turnaround time. PMID- 27249522 TI - Prevalence of Escherichia coli adhesion-related genes in neonatal calf diarrhea in Uruguay. AB - INTRODUCTION: Neonatal calf diarrhea (NCD), one of the most important diseases of neonatal dairy and beef calves in Uruguay, has become relevant in association with intensive systems. This disease generates substantial economic losses every year worldwide as a result of increased morbidity and mortality. Escherichia coli, one of the pathogens associated with NCD, can express several fimbrial and afimbrial adhesins. The objective of this study was to assess the presence of clpG, f5, f17A, f17G(II), and f17G(I) genes that encode three important adhesins expressed in diarrheagenic E. coli: F5, F17 and CS31A, isolated from feces of calves in Uruguay. METHODOLOGY: Feces of 86 (70 diarrheic and 16 healthy) calves, from 15 animal facilities in Uruguay, were collected between 2012 and 2013. Biochemical and molecular identification were performed to finally obtain 298 E. coli isolates. Partial amplification of adhesion-related genes was performed by polymerase chain reaction. RESULTS: The most prevalent gene was f17A (31.2%), followed by f17G(II), clpG, f17G(I) and f5 (25.8%, 17.5%, 3.7% and 0.7%, respectively). All genes were present in diarrheic and healthy animals except f5 and f17G(I); these genes were present only in affected calves, although in low numbers. CONCLUSIONS: This is the first report of the presence of F5, F17, and CS31A genes in E. coli strains from NCD cases in Uruguay. Prevalence values of the genes, except f5, were in accordance with regional findings. It is expected that further characterization of locally transmitted strains will contribute to control a problem of regional and international magnitude. PMID- 27249523 TI - Clinical and microbiological findings of infective endocarditis. AB - INTRODUCTION: Infective endocarditis (IE) is an infection that develops on the endothelial surface of the heart. Endocarditis is a major problem for the clinicians despite of the developments in diagnostic, surgical, and medical treatment methods. In this study, we aimed to evaluate symptoms, laboratory findings, treatment options, and clinical endpoint of the patients who were diagnosed with IE in a tertiary healthcare organization according to the literature data. METHODOLOGY: Between January 2006 and March 2013, 80 IE patients who were diagnosed and treated in accordance with modified Duke criteria were enrolled in the study. Demographic features, symptoms, and laboratory and echocardiographic findings were recorded after reviewing the patient files. RESULTS: The mean age of the patients was 51.3 +/- 16.0, and IE was more common in men (n = 56; 70%). Of 41 patients who had positive blood cultures, 20 patients had Staphylococcus spp. (48.7%) and 8 patients had Streptococcus spp. (19.5%). Brucella spp. was isolated from 5 patients (12.2%). While 48.7% (n = 39) of the patients had cardiac complications, 22 patients (27.5%) had embolic complication. Hospital mortality was observed in 20 patients (15%). CONCLUSIONS: In our patients, endocarditis was seen at a young age, and staphylococci were the most frequently isolated microorganism from blood culture. There were more patients with Brucella endocarditis compared to the general population. Complications are frequently seen in the course of endocarditis, and they cause problems for the clinicians during follow ups due to the high mortality rate of IE. PMID- 27249524 TI - Mortality risk factors show similar trends in modern and historic populations exposed to plague. AB - INTRODUCTION: Plague has been responsible for two major historic pandemics (6th 8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered. METHODOLOGY: The risk of mortality of the Malagasy population with those obtained from the reconstruction of three samples of European populations exposed to the historic pandemics was contrasted. RESULTS: The evidence shows that the risks of death are not uniform across age neither in modern nor in historic populations exposed to plague and shows precise concentrations in specific age groups (children between five and nine years of age and young adults). CONCLUSIONS: Although in the post-antibiotic era, the fatality rates have drastically reduced, both modern and historic populations were exposed to the same risk factors that are essentially represented by a low standard of environmental hygiene, poor nutrition, and weak health systems. PMID- 27249525 TI - Antimicrobial and anti-inflammatory potential therapy for opportunistic microorganisms. AB - INTRODUCTION: Methanolic extracts of six plants (Arbutus andrachne, Chrysanthemum coronarium, Inula viscosa, Origanum syriacum, Punica granatum, and Rosmarinus officinalis) used in traditional medicine for the treatment of bacterial and fungal infections were evaluated. The present study was conducted to evaluate the antimicrobial and anti-inflammatory activity of some medicinal plants in lowering the risk of opportunistic infections of the oral cavity caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Extracts were evaluated separately and in a mixture. METHODOLOGY: The methanolic plant extracts were tested against three opportunistic microorganisms by determining the minimum inhibitory concentration (MIC). They were also evaluated for their ability to suppress the release of the pro-inflammatory cytokine IL-6 while not suppressing the release of the anti-inflammatory cytokine IL-10 from peripheral blood mononuclear cells using ELISA. RESULTS: All extracts showed both antimicrobial and anti-inflammatory activities. However, O. syriacum exhibited the highest antimicrobial activity for the three microorganisms among all of the tested extracts (MIC S. aureus: 1 mg/mL; P. aeruginosa: 2 mg/mL; and C. albicans: 1 mg/mL). The extracts inhibited the expression of the pro-inflammatory cytokine IL 6 with apparent dose-dependent responses while they attenuated the secretion of the anti-inflammatory cytokine IL-10. The mixture of O. syriacum and R. officinalis showed an anti-inflammatory effect, with a synergistic antimicrobial effect. CONCLUSION: These findings support the idea that a diet rich in plants and herbs may contribute to the reduction of inflammation and microbial growth and may also be preventive against various infections, including those related to the oral cavity. PMID- 27249526 TI - An outbreak of dermatophilosis and caseous lymphadenitis mixed infection in camels (Camelus dromedaries) in Jordan. AB - INTRODUCTION: This study describes and reports, for the first time, an outbreak of dermatophilosis that occurred concurrently with caseous lymphadenitis involving two camel herds (Camelus dromedaries) in north Jordan. METHODOLOGY: The affected animals were part of two herds comprising 52 Arabian camels in herd 1 and 65 camels in herd 2. The age of infected camels ranged from 18 months to 5 years. Pus and skin scab samples were aseptically collected and bacteriologically examined. Affected camels were treated by long-acting oxytetracycline injection in a dose rate of 10 mg/kg body weight every 48 hours for three successive treatments, and local antiseptic and antibiotic cutaneous spray treatment for five successive days. RESULTS: The main clinical signs on affected camels were skin dermatitis and abscess formation. The isolated organisms were Dermatophilus congolensis and Corynebacterium pseudotuberculosis were the causative agents of dermatophilosis and caseous lymphadenitis, respectively. Other organisms were isolated from skin abscesses, including alpha-hemolytic streptococci, hemolytic E. coli, Actinomyces pyogenes, and S. aureus. The affected camels were rapidly and effectively cured by the above-mentioned treatment protocol. No mortality was recorded. CONCLUSIONS: Introducing purchased camels from animal auctions without pre-examination and keeping camels in over-crowded small barns under cold, humid, and rainy conditions during winter may predispose the eruption of mixed infection of dermatophilosis and caseous lymphadenitis. Treatment by long-acting oxytetracycline injection with local antiseptic and antibiotic cutaneous spray can control such infection. A survey on camel herds raised near Jordan's borders is needed to monitor the possibility of emerging infectious disease. PMID- 27249527 TI - Alterations in neutrophil extracellular traps is associated with the degree of decompensation of liver cirrhosis. AB - INTRODUCTION: Liver cirrhosis (LC) constitutes one of the main 10 causes of death worldwide. LC has a characteristic asymptomatic compensated phase followed by a progressive decompensated phase, in which diverse complications are presented. LC patients are highly prone to bacterial infections. The neutrophils in these patients present defects in the production of oxygen radicals, which are essential for bacteria elimination as in the activation of neutrophil extracellular traps (NETs). The main objective of this work was to determine the NETs and neutrophil activation markers in LC patients. METHODOLOGY: Neutrophil purification was done with Ficoll Histopaque from a sample of the peripheral blood of patients with compensated and decompensated LC. Neutrophils were activated with Phorbol 12-myristate 13-acetate to evaluate the release of NETs by means of fluorescence microscopy and fluorometry, while expression of activation markers (CD69, CD80, perforin, and CAP-18) was evaluated by flow cytometry. RESULTS: A significant decrease in the release capability of NETs was observed as the level of LC in the patient increased. When comparing serum levels in inflammatory cytokines among the different study groups, significant differences were observed. No significant differences were detected on neutrophil activation markers; nevertheless, there was a correlation between diminution of CD69 and CD80 expression in decompensated patients. CONCLUSIONS: We demonstrated that LC patients with neutrophil extracellular trap release deficiencies could have an increased rate of complications. PMID- 27249528 TI - Reducing bacterial contamination in an Orthopedic Theatre ventilated by natural ventilation, in a Developing Country. AB - INTRODUCTION: All surgical procedures have the potential for infection and some of the main sources are contamination from airborne particles, theatre personnel and the theatre environment. There is strong evidence that the use of ultra clean air flow systems in orthopedic operating theatres reduces the incidence of deep sepsis after surgery. In the developing world however, this is often an unrealistic solution. The aim of this study was to establish baseline levels of contamination in a working orthopedic theatre, at the Queen Elizabeth Central Hospital, Blantyre, Malawi. To feedback results to the theatre team, promote infection prevention discussion and work with the team to implement workable and realistic goals to improve the intra-operative environment. METHODOLOGY: Samples were collected from theatre equipment available at the time of surgery, from theatre water and theatre air using passive air sampling techniques. Samples were immediately transferred to the Central Microbiology Laboratory for culture on basic culture media. RESULTS: Bacterial contamination of theatre equipment, intra operative theatre air and water was detected. Results were discussed with the theatre and infection prevention team who were receptive to feedback with regards to infection prevention strategies and keen to develop simple measures which could be put in place to change practice. CONCLUSIONS: In this setting, we suggest that implementing workable and realistic goals such as, establishing baseline rates of bacterial contamination and introduction of strict protocols for asepsis and theatre etiquette, may reduce bacterial contamination rates and subsequent intra-operative infection in the absence of expensive engineering solutions. PMID- 27249529 TI - HCV non-1b genotypes in injecting drug users from Romania. AB - INTRODUCTION: Chronic hepatitis C cases diagnosed in Romania were mostly related to unsafe parenteral treatments and blood transfusions; HCV genotype 1b was prevalent. During the last decade, an increasing number of HCV infections was reported among people who inject drugs (PWID). The aim of the current study was to test if this epidemiological shift triggered a diversification of the circulating viral strains. METHODOLOGY: HCV genotypes were determined by reverse hybridization in 130 HCV-infected PWID (87.7% males; mean age 27.9 +/- 6.7 years, injecting drugs for 8.1 +/- 4.8 years). RESULTS: HIV-HCV co-infection was diagnosed in 80.8% of the subjects and 26.9% were HIV-HCV-HBV triple infected. Active HCV viral replication was present in 104 PWID (80%), more frequently in those HIV-co-infected (91.4% vs. 52% in HCV mono-infected, and 77.148.5% in HIV HCV-HBV triple-infected, p = 0.0001). Non-1b genotypes were prevalent (54.8%), with subtype 1a the most commonly detected (24%), followed by genotypes 3a (14.4%) and 4 (7.7%). Mixed infections with genotypes 1a and 1b were found in nine subjects (8.7%). There was no difference in the genotypes frequencies based on HIV or HBV co-infection status, length of drug usage, or associated risk factors (tattoos, piercing, detention). CONCLUSION: The continuous surveillance of HCV genotypes in PWID from Romania will add valuable information to the overall European epidemiological picture, with important therapeutic implications. PMID- 27249530 TI - Pediatric invasive disease due to Haemophilus influenzae serogroup A in Riyadh, Saudi Arabia: case series. AB - We describe the first two cases of invasive disease caused by Haemophilus influenzae serotype A in Saudi Arabia. This is the first known reported invasive Haemophilus influenzae serotype A from Saudi Arabia. CASE PRESENTATION: A ten month-old and three-month-old male not known to have any past history of any medical illness and who had received H. influenzae type b (Hib) vaccine presented to our hospital mainly with fever of few days' duration. A provisional diagnosis of meningitis with sepsis was made and laboratory tests were requested. The chest radiograph was normal. The laboratory results revealed leukocytosis, but leukopenia was noticed in the younger infant. Blood culture and cerebrospinal fluid specimens yielded a pure culture of Haemophilus influenzae and serotyping showed the isolates to be serogroup A. Both patients were started on vancomycin and third-generation cephalosporin. On receiving the blood culture result, vancomycin was stopped. Fever subsided after 48 hours, while in the second case, it continued for 12 days from the admission date. The repeat blood cultures were negative. Antibiotic therapy was given for 10 days for the first case with an unremarkable hospital course, while the second case was complicated by seizure and received a longer duration of antibiotics. Both infants were discharged home in good condition. CONCLUSIONS: Invasive non-typeable H. influenzae strains are emerging and there is a need for surveillance of this disease. This has implications in future vaccine development. PMID- 27249531 TI - A rare fatal case of a novel bunyavirus-associated hemophagocytic lymphohistiocytosis. AB - Herein we describe a rare fatal case of a novel bunyavirus-associated hemophagocytic lymphohistiocytosis (HLH) in a 62-year-old female patient. The novel bunyavirus infects patients with or without HLH who have similar clinical features such as fever, thrombocytopenia, and leukocytopenia. Therefore, the diagnosis of HLH can be easily missed. When HLH occurs, the disease worsens and the fatality rate rises. Our finding highlights the importance of bone marrow biopsy performed as soon as possible for patients suspected of having a novel bunyavirus infection and showing marked cytopenia in three cell lines. PMID- 27249532 TI - Ebola virus disease: Case management in the Institute of Infectious Diseases, University Hospital of Sassari, Sardinia, Italy. AB - Since the onset of the worst epidemic of Ebola virus disease in December 2013, 28,637 cases were reported as confirmed, probable, or suspected. Since the week of 3 January 2016, no more cases have been reported. The total number of deaths have amounted to 11,315 (39.5%). In developed countries, seven cases have been diagnosed: four in the United States, one in Spain, one in the United Kingdom, and one in Italy. On 20 July 2015, Italy was declared Ebola-free. On 9 May 2015, an Italian health worker came back to Italy after a long stay in Sierra Leone working for a non-governmental organization. Forty-eight hours after his arrival, he noticed headache, weakness, muscle pains, and slight fever. The following day, he was safely transported to the Infectious Diseases Unit of University Hospital of Sassari. The patient was hospitalized for 19 hours until an Italian Air Force medical division transferred him to Rome, to the Lazzaro Spallanzani Institute. Nineteen people who had contacts with the patient were monitored daily for 21 days by the Public Health Office of Sassari and none presented any symptoms. So far, neither vaccine nor treatment is available to be proposed on an international scale. Ebola is considered a re-emerging infectious disease which, unlike in the past, has been a worldwide emergency. This case study aimed to establish a discussion about the operative and logistic difficulties to be faced and about the discrepancy arising when protocols clash with the reality of facts. PMID- 27249533 TI - Monitoring Enzymatic Reactions in Real Time Using Venturi Easy Ambient Sonic Spray Ionization Mass Spectrometry. AB - We developed a technique to monitor spatially confined surface reactions with mass spectrometry under ambient conditions, without the need for voltage or organic solvents. Fused-silica capillaries immersed in an aqueous solution, positioned in close proximity to each other and the functionalized surface, created a laminar flow junction with a resulting reaction volume of ~5 pL. The setup was operated with a syringe pump, delivering reagents to the surface through a fused-silica capillary. The other fused-silica capillary was connected to a Venturi easy ambient sonic-spray ionization source, sampling the resulting analytes at a slightly higher flow rate compared to the feeding capillary. The combined effects of the inflow and outflow maintains a chemical microenvironment, where the rate of advective transport overcomes diffusion. We show proof-of concept where acetylcholinesterase was immobilized on an organosiloxane polymer through electrostatic interactions. The hydrolysis of acetylcholine by acetylcholinesterase into choline was monitored in real-time for a range of acetylcholine concentrations, fused-silica capillary geometries, and operating flow rates. Higher reaction rates and conversion yields were observed with increasing acetylcholine concentrations, as would be expected. PMID- 27249534 TI - Nanoparticle Surface Affinity as a Predictor of Trophic Transfer. AB - Nanoscale materials, whether natural, engineered, or incidental, are increasingly acknowledged as important components in large, environmental systems with potential implications for environmental impact and human health. Mathematical models are a useful tool for handling the rapidly increasing complexity and diversity of these materials and their exposure routes. Presented here is a mathematical model of trophic transfer driven by nanomaterial surface affinity for environmental and biological surfaces, developed in tandem with an experimental functional assay for determining these surface affinities. We found that nanoparticle surface affinity is a strong predictor of uptake through predation in a simple food web consisting of the algae Chlorella vulgaris and daphnid Daphnia magna. The mass of nanoparticles internalized by D. magna through consuming nanomaterial-contaminated algae varied linearly with surface-attachment efficiency. Internalized quantities of gold nanoparticles in D. magna ranged from 8.3 to 23.6 ng/mg for nanoparticle preparations with surface-attachment efficiencies ranging from 0.07 to 1. This model, coupled with the functional assay approach, may provide a useful screening tool for existing materials as well as a predictive model for their development. PMID- 27249536 TI - In Vitro Selection of Chromium-Dependent DNAzymes for Sensing Chromium(III) and Chromium(VI). AB - Chromium is a very important analyte for environmental monitoring, and developing biosensors for chromium is a long-standing analytical challenge. In this work, in vitro selection of RNA-cleaving DNAzymes was carried out in the presence of Cr(3+) . The most active DNAzyme turned out to be the previously reported lanthanide-dependent Ce13d DNAzyme. Although the Ce13d activity was about 150 fold lower with Cr(3+) than that with lanthanides, the activity of lanthanides and other competing metals was masked by using a phosphate buffer; this left Cr(3+) as the only metal that could activate Ce13d. With 100 MUm Cr(3+) , the cleavage rate is 1.6 h(-1) at pH 6. By using a molecular beacon design, Cr(3+) was measured with a detection limit of 70 nm, which was significantly lower than the United States Environmental Protection Agency (EPA) limit (11 MUm). Cr(4+) was measured after reduction by NaBH4 to Cr(3+) , and it could be sensed with a similar detection limit of 140 nm Cr(4+) ; this value was lower than the EPA limit of 300 nm. This sensor was tested for chromium speciation analysis in a real sample, and the results supported its application for environmental monitoring. At the same time, it has enhanced our understanding of the interactions between chromium and DNA. PMID- 27249535 TI - Effects of uncomplicated carotid endarterectomy on cognitive function and brain perfusion in patients with unilateral asymptomatic severe stenosis of the internal carotid artery by comparison with unoperated patients. AB - OBJECTIVE: The purpose of the present exploratory study was to evaluate the effects of uncomplicated carotid endarterectomy (CEA) on cognitive function and brain perfusion in patients with unilateral asymptomatic severe stenosis of the internal carotid artery (ICA) by comparison with unoperated patients. METHODS: Patients with age <=75 years and unilateral asymptomatic severe stenosis (>=70%) of the cervical ICA underwent CEA with antiplatelet therapy (surgically treated group: 116 patients) or antiplatelet therapy alone or neither (medically treated group: 45 patients). For the surgically treated group, neuropsychological testing and brain perfusion measurement using single-photon emission computed tomography were performed within one month before surgery and one month after surgery. For the medically treated group, the same testing and measurement were performed twice at an interval of 1 to 2 months. RESULTS: None of the operated patients developed new major ischemic events after surgery or intraoperative cerebral hyperperfusion. None of the patients in the medically treated group experienced neurological deficits including transient ischemic attacks during the study period. The incidence of patients with interval cognitive improvement was significantly greater in the surgically treated group (11 patients: 9%) than in the medically treated group (0%) (p = 0.0352). The incidence of patients with interval brain perfusion improvement in the ipsilateral cerebral hemisphere was significantly greater in the surgically treated group (24 patients: 21%) than in the medically treated group (0%) (p = 0.0003). CONCLUSIONS: Uncomplicated CEA may improve cognitive function and brain perfusion in patients with unilateral asymptomatic severe stenosis of the ICA when compared with unoperated patients. PMID- 27249537 TI - Prevalence and Nature of Hearing Loss in 22q11.2 Deletion Syndrome. AB - PURPOSE: The purpose of this study was to clarify the prevalence, type, severity, and age-dependency of hearing loss in 22q11.2 deletion syndrome. METHOD: Extensive audiological measurements were conducted in 40 persons with proven 22q11.2 deletion (aged 6-36 years). Besides air and bone conduction thresholds in the frequency range between 0.125 and 8.000 kHz, high-frequency thresholds up to 16.000 kHz were determined and tympanometry, acoustic reflex (AR) measurement, and distortion product otoacoustic emission (DPOAE) testing were performed. RESULTS: Hearing loss was identified in 59% of the tested ears and was mainly conductive in nature. In addition, a high-frequency sensorineural hearing loss with down-sloping curve was found in the majority of patients. Aberrant tympanometric results were recorded in 39% of the ears. In 85% of ears with a Type A or C tympanometric peak, ARs were absent. A DPOAE response in at least 6 frequencies was present in only 23% of the ears with a hearing threshold <=30 dB HL. In patients above 14 years of age, there was a significantly lower percentage of measurable DPOAEs. CONCLUSION: Hearing loss in 22q11.2 deletion syndrome is highly prevalent and both conductive and high-frequency sensorineural in nature. The age-dependent absence of DPOAEs in 22q11.2 deletion syndrome suggests cochlear damage underlying the high-frequency hearing loss. PMID- 27249538 TI - Macroporous Polymers with Aligned Microporous Walls from Pickering High Internal Phase Emulsions. AB - A novel class of macroporous polymers, open macroporous polymers with aligned microporous void walls, were prepared by combining particle-stabilized high internal phase emulsion (Pickering HIPE) and unidirectional freezing technique. These Pickering HIPEs were prepared by utilizing poly(urethane urea)/(vinyl ester resin) nanoparticles as the sole stabilizer, and this nanoparticles also acted as building blocks for the resulting macroporous polymers. Moreover, the morphology and compression modulus of the resulting porous materials could be tuned easily. This means now Pickering-HIPE templated open-cell foams can be prepared, and this route was normally achieved with surfactant and/or chemical reaction involved. PMID- 27249539 TI - Characterizing the boundary lateral to the shear direction of deformation twins in magnesium. AB - The three-dimensional nature of twins, especially the atomic structures and motion mechanisms of the boundary lateral to the shear direction of the twin, has never been characterized at the atomic level, because such boundary is, in principle, crystallographically unobservable. We thus refer to it here as the dark side of the twin. Here, using high-resolution transmission electron microscopy and atomistic simulations, we characterize the dark side of deformation twins in magnesium. It is found that the dark side is serrated and comprised of coherent twin boundaries and semi-coherent twist prismatic-prismatic boundaries that control twin growth. The conclusions of this work apply to the same twin mode in other hexagonal close-packed materials, and the conceptual ideas discussed here should hold for all twin modes in crystalline materials. PMID- 27249541 TI - The Spectrum of Caregiving in Palliative Care for Serious, Advanced, Rare Diseases: Key Issues and Research Directions. AB - Rare diseases are often life-limiting conditions, the majority of which require constant caregiving needs. The realization of a spectrum of palliative care throughout the trajectory of rare diseases could ensure individualized and caregiver-focused approaches to the care of patients and families. In June 2015, the National Institute of Nursing Research (NINR), the lead institute at the National Institutes of Health for end-of-life research, in conjunction with the National Center for Advancing Translational Sciences, Office of Rare Diseases Research (ORDR) held an interdisciplinary workshop on the unique challenges of caregiving and palliative care in adult and pediatric rare diseases. The panel identified gaps in current knowledge, and afforded suggestions for research opportunities in palliative care science to improve the care of individuals with serious, advanced, rare diseases and their caregivers. This meeting provided an in-depth opportunity to incorporate new concepts into palliative and end-of-life care for individuals with a range of rare diseases and their caregivers. This report presents a summary of the workshop. PMID- 27249542 TI - Advancing pharmacologic treatment options for pharmacologic treatment options for children with epilepsy. AB - INTRODUCTION: The pharmacological management of epilepsy is continually modified by the increase in our knowledge about the efficacy and the safety on antiepileptic drugs. AREAS COVERED: This review covers the published data (2010 2015) on the pharmacological management of epilepsy in children and adolescent. We review the data from the most recent randomized controlled and open-label trials. EXPERT OPINION: Even if there is an increasing number of antiepileptic drugs approved for focal seizure in children and adolescent with epilepsy, each new approval would be considered as a significant addition to the current therapeutic options. Refractory epilepsy with focal seizure should not be regarded as a single disease but as numerous various patients. Because most of evidence of efficacy is primarily from placebo-controlled trials, there is no evidence to choose a treatment based on efficacy. In case of focal seizure, we explain how possible cognitive impact, mechanisms of action, pharmacologic characteristics and side effect profile are the factors taken into an account to propose a treatment. In case of childhood absence epilepsy, there are evidences showing the ethosuximide should be the first line treatment. Finally, we stress that trials in the pediatric epilepsy syndromes are required to propose better evidence-based pharmacological management. PMID- 27249540 TI - Non-Metabolic Role of PKM2 in Regulation of the HIV-1 LTR. AB - Identification of cellular proteins, in addition to already known transcription factors such as NF-kappaB, Sp1, C-EBPbeta, NFAT, ATF/CREB, and LEF-1, which interact with the HIV-1 LTR, is critical in understanding the mechanism of HIV-1 replication in monocytes/macrophages. Our studies demonstrate upregulation of pyruvate kinase isoform M2 (PKM2) expression during HIV-1SF162 infection of monocyte/macrophages and reactivation of HIV-1 in U1 cells, a macrophage model of latency. We observed that HIV-1SF162 infection of monocyte/macrophages and reactivation of HIV-1 in U1 cells by PMA resulted in increased levels of nuclear PKM2 compared to PMA-induced U937 cells. Furthermore, there was a significant increase in the nuclear dimeric form of PKM2 in the PMA-induced U1 cells in comparison to PMA-induced U937 cells. We focused on understanding the potential role of PKM2 in HIV-1 LTR transactivation. Chromatin immunoprecipitation (ChIP) analysis in PMA-activated U1 and TZM-bl cells demonstrated the interaction of PKM2 with the HIV-1 LTR. Our studies show that overexpression of PKM2 results in transactivation of HIV-1 LTR-luciferase reporter in U937, U-87 MG, and TZM-bl cells. Using various truncated constructs of the HIV-1 LTR, we mapped the region spanning -120 bp to -80 bp to be essential for PKM2-mediated transactivation. This region contains the NF-kappaB binding site and deletion of this site attenuated PKM2-mediated activation of HIV-1 LTR. Immunoprecipitation experiments using U1 cell lysates demonstrated a physical interaction between PKM2 and the p65 subunit of NF-kappaB. These observations demonstrate for the first time that PKM2 is a transcriptional co-activator of HIV-1 LTR. J. Cell. Physiol. 232: 517 525, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27249543 TI - Separate Evaluation of the Ipsilateral and Contralateral MR Fetal Lung Volume in Patients With Congenital Diaphragmatic Hernia. AB - OBJECTIVE: Our study had two objectives. First, we separately evaluated observed to-expected MR fetal lung volume (FLV) of lungs ipsilateral and contralateral to a congenital diaphragmatic hernia (CDH). Second, we compared the prognostic value of observed-to-expected MR FLV of the ipsilateral and contralateral lungs with that of observed-to-expected MR FLV of both lungs with respect to survival, need for extracorporeal membrane oxygenation (ECMO), and development of chronic lung disease (CLD). MATERIALS AND METHODS: We evaluated observed-to-expected MR FLV of the lung ipsilateral to the diaphragmatic defect as well as in the contralateral lung in 107 fetuses with isolated CDH. ROC analysis and logistic regression analysis were performed to assess the prognostic value of the observed-to expected MR FLV for association with outcome. RESULTS: In all fetuses with CDH, values in the ipsilateral (mean observed-to-expected MR FLV +/- SD, 9.4% +/- 9.6%) and the contralateral lung (mean observed-to-expected MR FLV, 48.9% +/- 18.5%; p < 0.0001) were significantly lower than values measured in healthy fetuses. Observed-to-expected MR FLV of both lungs and of the contralateral and ipsilateral lung revealed significant differences regarding survival (p < 0.0001, p < 0.0001, and p = 0.0170, respectively), need for ECMO (p < 0.0001, p < 0.0001, and p = 0.0051, respectively), and development of CLD (p = 0.0004, p = 0.0002, and p = 0.0460, respectively). Compared with the observed-to-expected MR FLV of both lungs, the observed-to-expected MR FLV of the contralateral lung showed a slightly higher prognostic accuracy regarding survival (AUC = 0.859 vs 0.825) and development of CLD (AUC = 0.734 vs 0.732) and a similar prognostic accuracy regarding need for ECMO (AUC = 0.805 vs 0.826). Observed-to-expected MR FLV of the ipsilateral lung did not show good prognostic value regarding survival (AUC = 0.617), need for ECMO (AUC = 0.673), and development of CLD (AUC = 0.636). These AUCs were significantly smaller than the AUCs resulting from the observed-to expected MR FLV of both lungs (each p < 0.05) and considerably smaller than the AUCs of the observed-to-expected MR FLV of the contralateral lung (each p < 0.10). CONCLUSION: Patients with CDH showed a substantially lower observed-to expected MR FLV of both lungs compared with healthy fetuses. The observed-to expected MR FLV of both lungs as well as of the lung contralateral to the CDH were reliable prenatal predictors of survival, need for ECMO, and development of CLD. PMID- 27249544 TI - Ultrathin Laminar Ir Superstructure as Highly Efficient Oxygen Evolution Electrocatalyst in Broad pH Range. AB - Shape-controlled noble metal nanocrystals (NCs), such as Au, Ag, Pt, Pd, Ru, and Rh are of great success due to their new and enhanced properties and applications in chemical conversion, fuel cells, and sensors, but the realization of shape control of Ir NCs for achieving enhanced electrocatalysis remains a significant challenge. Herein, we report an efficient solution method for a new class of three-dimensional (3D) Ir superstructure that consists of ultrathin Ir nanosheets as subunits. Electrochemical studies show that it delivers the excellent electrocatalytic activity toward oxygen evolution reaction (OER) in alkaline condition with an onset potential at 1.43 V versus reversible hydrogen electrode (RHE) and a very low Tafel slope of 32.7 mV decade(-1). In particular, it even shows superior performance for OER in acidic solutions with the low onset overpotential of 1.45 V versus RHE and small Tafel slope of 40.8 mV decade(-1), which are much better than those of small Ir nanoparticles (NPs). The 3D Ir superstructures also exhibit good stability under acidic condition with the potential shift of less than 20 mV after 8 h i-t test. The present work highlights the importance of tuning 3D structures of Ir NCs for enhancing OER performance. PMID- 27249545 TI - Resilience, religiosity and treatment adherence in hemodialysis patients: a prospective study. AB - Resilience and religiosity have received attention as an important process in the experience and management of chronic comorbidities; however, there is no study evaluating resilience in hemodialysis patients and its association with other psychological dimensions or with treatment adherence. This observational prospective study assessed resilience (25 item Wagnild and Young Resilience Scale), religiosity under three dimensions (organizational, non-organizational and intrinsic) using DUREL scale, depressive symptoms (Patient Health Questionnaire-9) and health-related quality of life (Short Form-36 questionnaire). The main outcomes were medication adherence using the Morisky Medication Adherence Scale-8 (MMAR-8) and the missing/shortened dialysis sessions in the following six months. Of 208 patients approached, 202 (97.1%) agreed to participate. One hundred twenty-three patients (60.9%) were males and mean age was 52.8 +/- 14.8 years-old. The median time on hemodialysis was 36 months (IQR, 12, 84). 82 (40.6%) patients obtained a MMAS-8 score <6 and were considered as having 'poor adherence'. Overall, the mean score of medication adherence was low (5.7 +/- 2.1). About adherence to hemodialysis sessions, patients missed a total of 234 (1.6%) hemodialysis sessions. Forty-eight patients (23.7%) missed an average of at least three sessions in six months. Regarding adherence to medication, there was no association in the uni- or multivariate analysis between religiosity dimensions and MMAS-8 score. After adjustment, resilience was positively associated with MMAS-8 score (standardized beta coefficient .239, p = .016). Organized and intrinsic religiosity were associated with adherence to dialysis sessions (standardized beta coefficient .258, p = .004 and .231, p = .026, respectively). Interestingly, opposite to medication adherence, more resilient patients were associated with less adherence to hemodialysis sessions (standardized beta coefficient -.296, p = .001). Religiosity was associated with dialysis adherence but not with medication adherence. Resilience was associated with higher medication adherence but lower adherence to dialysis sessions. PMID- 27249546 TI - Effect of Clustering Algorithm on Establishing Markov State Model for Molecular Dynamics Simulations. AB - Recently, the Markov state model has been applied for kinetic analysis of molecular dynamics simulations. However, discretization of the conformational space remains a primary challenge in model building, and it is not clear how the space decomposition by distinct clustering strategies exerts influence on the model output. In this work, different clustering algorithms are employed to partition the conformational space sampled in opening and closing of fatty acid binding protein 4 as well as inactivation and activation of the epidermal growth factor receptor. Various classifications are achieved, and Markov models are set up accordingly. On the basis of the models, the total net flux and transition rate are calculated between two distinct states. Our results indicate that geometric and kinetic clustering perform equally well. The construction and outcome of Markov models are heavily dependent on the data traits. Compared to other methods, a combination of Bayesian and hierarchical clustering is feasible in identification of metastable states. PMID- 27249547 TI - Hierarchical graphene-polyaniline nanocomposite films for high-performance flexible electronic gas sensors. AB - A hierarchically nanostructured graphene-polyaniline composite film is developed and assembled for a flexible, transparent electronic gas sensor to be integrated into wearable and foldable electronic devices. The hierarchical nanocomposite film is obtained via aniline polymerization in reduced graphene oxide (rGO) solution and simultaneous deposition on flexible PET substrate. The PANI nanoparticles (PPANI) anchored onto rGO surfaces (PPANI/rGO) and the PANI nanofiber (FPANI) are successfully interconnected and deposited onto flexible PET substrates to form hierarchical nanocomposite (PPANI/rGO-FPANI) network films. The assembled flexible, transparent electronic gas sensor exhibits high sensing performance towards NH3 gas concentrations ranging from 100 ppb to 100 ppm, reliable transparency (90.3% at 550 nm) for the PPANI/rGO-FPANI film (6 h sample), fast response/recovery time (36 s/18 s), and robust flexibility without an obvious performance decrease after 1000 bending/extending cycles. The excellent sensing performance could probably be ascribed to the synergetic effects and the relatively high surface area (47.896 m(2) g(-1)) of the PPANI/rGO FPANI network films, the efficient artificial neural network sensing channels, and the effectively exposed active surfaces. It is expected to hold great promise for developing flexible, cost-effective, and highly sensitive electronic sensors with real-time analysis to be potentially integrated into wearable flexible electronics. PMID- 27249548 TI - Is Early Bariatric Surgery the Answer for Diabetes in Obesity? PMID- 27249550 TI - Predicting and measuring fluid responsiveness with echocardiography. AB - Echocardiography is ideally suited to guide fluid resuscitation in critically ill patients. It can be used to assess fluid responsiveness by looking at the left ventricle, aortic outflow, inferior vena cava and right ventricle. Static measurements and dynamic variables based on heart-lung interactions all combine to predict and measure fluid responsiveness and assess response to intravenous fluid resuscitation. Thorough knowledge of these variables, the physiology behind them and the pitfalls in their use allows the echocardiographer to confidently assess these patients and in combination with clinical judgement manage them appropriately. PMID- 27249549 TI - The role of TTE in assessment of the patient before and following TAVI for AS. AB - Transcatheter aortic valve implantation is now accepted as a standard mode of treatment for an increasingly large population of patients with severe aortic stenosis. With the availability of this technique, echocardiographers need to be familiar with the imaging characteristics that can help to identify which patients are best suited to conventional surgery or transcatheter aortic valve implantation, and what parameters need to be measured. This review highlights the major features that should be assessed during transthoracic echocardiography before presentation of the patient to the 'Heart Team'. In addition, this review summarises the aspects to be considered on echocardiography during follow-up assessment after successful implantation of a transcatheter aortic valve. PMID- 27249551 TI - Left atrial strain: a new predictor of thrombotic risk and successful electrical cardioversion. AB - BACKGROUND: Left atrial deformation (LAD) parameters are new markers of atrial structural remodelling that seem to be affected in atrial fibrillation (AF) and atrial flutter (AFL). This study aimed to determine whether LAD can identify patients with a higher risk of thrombosis and unsuccessful electrical cardioversion (ECV). METHODS: Retrospective study including 56 patients with AF or AFL undergoing ECV, with previous transthoracic (TTE) and transoesophageal echocardiography (TEE) studies. Echocardiographic parameters analysed were as follows: left ventricle function, left atrium (LA) dimensions, LAD parameters (positive and negative strain peaks), left atrial appendage (LAA) filling and emptying velocities and the presence of thrombi. Strain values were analysed according to thrombotic risk and success of ECV. RESULTS: Lower mean values of peak-positive strain (PPS) in patients with prothrombotic velocities (<25 cm/s) and a higher incidence of thrombi in LAA were observed compared with those with normal velocities. Multivariate analysis revealed PPS normalised by LA maximum volume indexed by body surface area (BSA) to be associated with prothrombotic risk (odds ratio 0.000 (95% CI: 0.000-0.243), P 0.017), regardless of CHADs2VASC score. Peak-negative strain normalised by LA volumes indexed by BSA were associated with unsuccessful ECV. CONCLUSIONS: Atrial deformation parameters identify AF and AFL patients with a high risk of thrombosis and unsuccessful ECV. Therefore, these new parameters should be included in anticoagulation management and rhythm vs rate control strategies. PMID- 27249552 TI - Stress echocardiography in patients with morbid obesity. AB - The incidence of significant obesity is rising across the globe. These patients often have a clustering of cardiovascular risk factors and are frequently referred for noninvasive cardiac imaging tests. Stress echocardiography (SE) is widely used for assessment of patients with known or suspected coronary artery disease (CAD), but its clinical utility in morbidly obese patients (in whom image quality may suffer due to body habitus) has been largely unknown. The recently published Stress Ultrasonography in Morbid Obesity (SUMO) study has shown that SE, when performed appropriately with ultrasound contrast agents (whether performed with physiological or pharmacological stress), has excellent feasibility and appropriately risk stratifies morbidly obese patients, including identification of patients who require revascularization. This article reviews the evidence supporting the use of echocardiographic techniques in morbidly obese patients for assessment of known or suspected CAD and briefly discusses other noninvasive modalities, including magnetic resonance and nuclear techniques, comparing and contrasting these techniques against SE. PMID- 27249553 TI - Pulmonary transit time measurement by contrast-enhanced ultrasound in left ventricular dyssynchrony. AB - BACKGROUND: Pulmonary transit time (PTT) is an indirect measure of preload and left ventricular function, which can be estimated using the indicator dilution theory by contrast-enhanced ultrasound (CEUS). In this study, we first assessed the accuracy of PTT-CEUS by comparing it with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Secondly, we tested the hypothesis that PTT-CEUS correlates with the severity of heart failure, assessed by MRI and N-terminal pro B-type natriuretic peptide (NT-proBNP). METHODS AND RESULTS: Twenty patients referred to our hospital for cardiac resynchronization therapy (CRT) were enrolled. DCE-MRI, CEUS, and NT-proBNP measurements were performed within an hour. Mean transit time (MTT) was obtained by estimating the time evolution of indicator concentration within regions of interest drawn in the right and left ventricles in video loops of DCE-MRI and CEUS. PTT was estimated as the difference of the left and right ventricular MTT. Normalized PTT (nPTT) was obtained by multiplication of PTT with the heart rate. Mean PTT-CEUS was 10.5+/ 2.4s and PTT-DCE-MRI was 10.4+/-2.0s (P=0.88). The correlations of PTT and nPTT by CEUS and DCE-MRI were strong; r=0.75 (P=0.0001) and r=0.76 (P=0.0001), respectively. Bland-Altman analysis revealed a bias of 0.1s for PTT. nPTT-CEUS correlated moderately with left ventricle volumes. The correlations for PTT-CEUS and nPTT-CEUS were moderate to strong with NT-proBNP; r=0.54 (P=0.022) and r=0.68 (P=0.002), respectively. CONCLUSIONS: (n)PTT-CEUS showed strong agreement with that by DCE-MRI. Given the good correlation with NT-proBNP level, (n)PTT-CEUS may provide a novel, clinically feasible measure to quantify the severity of heart failure. CLINICAL TRIAL REGISTRY: NCT01735838. PMID- 27249554 TI - Traumatic avulsion of the tricuspid valve after gas bottle explosion. AB - SummaryWe present a very rare example of chronic right heart failure caused by torrent tricuspid regurgitation. Massive right heart dilatation and severe tricuspid regurgitation due to avulsion of the tricuspid valve apparatus occurred as a result of a blunt chest trauma following the explosion of a gas bottle 20 years before admission, when the patient was a young man in Vietnam. After this incident, the patient went through a phase of severe illness, which can retrospectively be identified as an acute right heart decompensation with malaise, ankle edema, and dyspnea. Blunt chest trauma caused by explosives leading to valvular dysfunction has not been reported in the literature so far. It is remarkable that the patient not only survived this trauma, but had been managing his chronic heart failure well without medication for over 20 years. LEARNING POINTS: Thorough clinical and physical examination remains the key to identifying patients with relevant valvulopathies.With good acoustic windows, TTE is superior to TEE in visualizing the right heart.Traumatic avulsion of valve apparatus is a rare but potentially life-threatening complication of blunt chest trauma and must be actively sought for. Transthoracic echocardiography remains the method of choice in these patients. PMID- 27249555 TI - The old and the new: the pivotal role of TTE in TAVI. PMID- 27249556 TI - Left ventricular mechanical dispersion is associated with nonsustained ventricular tachycardia in hypertrophic cardiomyopathy. AB - OBJECTIVE: We assessed the value of speckle tracking two-dimensional (2D) strain echocardiography (2DSE) measured mechanical dispersion (MD) with other imaging and electrocardiographic parameters in differentiating hypertrophic cardiomyopathy (HCM) patients with and without nonsustained ventricular tachycardia (NSVT) on 24-h ambulatory ECG monitoring. METHODS AND RESULTS: We studied 31 patients with HCM caused by the Finnish founder mutation MYBPC3-Q1061X and 20 control subjects with comprehensive 2DSE echocardiography and cardiac magnetic resonance imaging (CMRI). The presence of NSVT was assessed from ambulatory 24-h ECG monitoring. NSVT episodes were recorded in 11 (35%) patients with HCM. MD was significantly higher in HCM patients with NSVT (93 +/- 41 ms) compared to HCM patients without NSVT (50 +/- 18 ms, p = 0.012) and control subjects (41 +/- 16 ms, p < 0.001). MD was the only variable independently associated with the presence of NSVT (OR: 1.60, 95% CI: 1.05-2.45, p = 0.030). Assessed by ROC curves, MD performed best in differentiating between HCM patients with and without NSVT (AUC = 0.81). CONCLUSIONS: Increased mechanical dispersion was associated with NSVT in HCM patients on 24-h ambulatory ECG monitoring. Key messages The prediction of sudden cardiac death in hypertrophic cardiomyopathy remains a challenge and novel imaging methods are required to identify individuals at risk of malignant ventricular arrhythmias. Mechanical dispersion by speckle tracking echocardiography is associated with NSVT on 24-h ambulatory ECG monitoring in patients with hypertrophic cardiomyopathy. PMID- 27249557 TI - Broadband Yellowish-Green Emitting Ba4Gd3Na3(PO4)6F2:Eu(2+) Phosphor: Structure Refinement, Energy Transfer, and Thermal Stability. AB - A series of Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphors with a broad emitting band have been synthesized by a traditional solid state reaction. The crystal structural and photoluminescence properties of Ba4Gd3Na3(PO4)6F2:Eu(2+) are investigated. The different crystallographic sites of Eu(2+) in Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphors have been verified by means of their photoluminescence (PL) properties and decay times. Energy transfer between Eu(2+) ions, analyzed by excitation, emission, and PL decay behavior, has been indicated to be a dipole-dipole mechanism. Moreover, the luminescence quantum yield as well as the thermal stability of the Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphor have been investigated systematically. The as-prepared Ba4Gd3Na3(PO4)6F2:Eu(2+) phosphor can act as a promising candidate for n-UV convertible white LEDs. PMID- 27249558 TI - Partial Least Square Discriminant Analysis Discovered a Dietary Pattern Inversely Associated with Nasopharyngeal Carcinoma Risk. AB - Evidence on the association between dietary component, dietary pattern and nasopharyngeal carcinoma (NPC) is scarce. A major challenge is the high degree of correlation among dietary constituents. We aimed to identify dietary pattern associated with NPC and to illustrate the dose-response relationship between the identified dietary pattern scores and the risk of NPC. Taking advantage of a matched NPC case-control study, data from a total of 319 incident cases and 319 matched controls were analyzed. Dietary pattern was derived employing partial least square discriminant analysis (PLS-DA) performed on energy-adjusted food frequencies derived from a 66-item food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multiple conditional logistic regression models, linking pattern scores and NPC risk. A high score of the PLS-DA derived pattern was characterized by high intakes of fruits, milk, fresh fish, vegetables, tea, and eggs ordered by loading values. We observed that one unit increase in the scores was associated with a significantly lower risk of NPC (ORadj = 0.73, 95% CI = 0.60-0.88) after controlling for potential confounders. Similar results were observed among Epstein-Barr virus seropositive subjects. An NPC protective diet is indicated with more phytonutrient-rich plant foods (fruits, vegetables), milk, other protein-rich foods (in particular fresh fish and eggs), and tea. This information may be used to design potential dietary regimen for NPC prevention. PMID- 27249559 TI - Study of the Microfocus X-Ray Tube Based on a Point-Like Target Used for Micro Computed Tomography. AB - For a micro-Computed Tomography (Micro-CT) system, the microfocus X-ray tube is an essential component because the spatial resolution of CT images, in theory, is mainly determined by the size and stability of the X-ray focal spot of the microfocus X-ray tube. However, many factors, including voltage fluctuations, mechanical vibrations, and temperature changes, can cause the size and the stability of the X-ray focal spot to degrade. A new microfocus X-ray tube based on a point-like micro-target in which the X-ray target is irradiated with an unfocused electron beam was investigated. EGS4 Monte Carlo simulation code was employed for the calculation of the X-ray intensity produced from the point-like micro-target and the substrate. The effects of several arrangements of the target material, target and beam size were studied. The simulation results demonstrated that if the intensity of X-rays generated at the point-like target is greater than half of the X-ray intensity produced on the substrate, the X-ray focal spot is determined in part by the point-like target rather than by the electron beam in the conventional X-ray tube. In theory, since it is able to reduce those unfavorable effects such as the electron beam trajectory swinging and the beam size changing for the microfocus X-ray tube, it could alleviate CT image artifacts caused by the X-ray focal spot shift and size change. PMID- 27249560 TI - Receptor-mediated sorting of soluble vacuolar proteins ends at the trans-Golgi network/early endosome. AB - The sorting of soluble proteins for degradation in the vacuole is of vital importance in plant cells, and relies on the activity of vacuolar sorting receptors (VSRs). In the plant endomembrane system, VSRs bind vacuole-targeted proteins and facilitate their transport to the vacuole. Where exactly these interactions take place has remained controversial, however. Here, we examine the potential for VSR-ligand interactions in all compartments of the vacuolar transport system in tobacco mesophyll protoplasts. To do this, we developed compartment-specific VSR sensors that assemble as a result of a nanobody-epitope interaction, and monitored the degree of ligand binding by analysing Forster resonance energy transfer using fluorescence lifetime imaging microscopy (FRET FLIM). We show that VSRs bind ligands in the endoplasmic reticulum (ER) and in the Golgi, but not in the trans-Golgi network/early endosome (TGN/EE) or multivesicular late endosomes, suggesting that the post-TGN/EE trafficking of ligands towards the vacuole is VSR independent. We verify this by showing that non-VSR-ligands are also delivered to the vacuole from the TGN/EE after endocytic uptake. We conclude that VSRs are required for the transport of ligands from the ER and the Golgi to the TGN/EE, and suggest that the onward transport to the vacuole occurs by default. PMID- 27249561 TI - Global conservation priorities for crop wild relatives. AB - The wild relatives of domesticated crops possess genetic diversity useful for developing more productive, nutritious and resilient crop varieties. However, their conservation status and availability for utilization are a concern, and have not been quantified globally. Here, we model the global distribution of 1,076 taxa related to 81 crops, using occurrence information collected from biodiversity, herbarium and gene bank databases. We compare the potential geographic and ecological diversity encompassed in these distributions with that currently accessible in gene banks, as a means to estimate the comprehensiveness of the conservation of genetic diversity. Our results indicate that the diversity of crop wild relatives is poorly represented in gene banks. For 313 (29.1% of total) taxa associated with 63 crops, no germplasm accessions exist, and a further 257 (23.9%) are represented by fewer than ten accessions. Over 70% of taxa are identified as high priority for further collecting in order to improve their representation in gene banks, and over 95% are insufficiently represented in regard to the full range of geographic and ecological variation in their native distributions. The most critical collecting gaps occur in the Mediterranean and the Near East, western and southern Europe, Southeast and East Asia, and South America. We conclude that a systematic effort is needed to improve the conservation and availability of crop wild relatives for use in plant breeding. PMID- 27249563 TI - Silencing in sperm cells is directed by RNA movement from the surrounding nurse cell. AB - Plant small interfering RNAs (siRNAs) communicate from cell to cell and travel long distances through the vasculature. However, siRNA movement into germ cells has remained controversial, and has gained interest because the terminally differentiated pollen vegetative nurse cell surrounding the sperm cells undergoes a programmed heterochromatin decondensation and transcriptional reactivation of transposable elements (TEs). Transcription of TEs leads to their post transcriptional degradation into siRNAs, and it has been proposed that the purpose of this TE reactivation is to generate and load TE siRNAs into the sperm cells. Here, we identify the molecular pathway of TE siRNA production in the pollen grain and demonstrate that siRNAs produced from pollen vegetative cell transcripts can silence TE reporters in the sperm cells. Our data demonstrates that TE siRNAs act non-cell-autonomously, inhibiting TE activity in the germ cells and potentially the next generation. PMID- 27249564 TI - State transitions redistribute rather than dissipate energy between the two photosystems in Chlamydomonas. AB - Photosynthesis converts sunlight into biologically useful compounds, thus fuelling practically the entire biosphere. This process involves two photosystems acting in series powered by light harvesting complexes (LHCs) that dramatically increase the energy flux to the reaction centres. These complexes are the main targets of the regulatory processes that allow photosynthetic organisms to thrive across a broad range of light intensities. In microalgae, one mechanism for adjusting the flow of energy to the photosystems, state transitions, has a much larger amplitude than in terrestrial plants, whereas thermal dissipation of energy, the dominant regulatory mechanism in plants, only takes place after acclimation to high light. Here we show that, at variance with recent reports, microalgal state transitions do not dissipate light energy but redistribute it between the two photosystems, thereby allowing a well-balanced influx of excitation energy. PMID- 27249562 TI - Local auxin metabolism regulates environment-induced hypocotyl elongation. AB - A hallmark of plants is their adaptability of size and form in response to widely fluctuating environments. The metabolism and redistribution of the phytohormone auxin play pivotal roles in establishing active auxin gradients and resulting cellular differentiation. In Arabidopsis thaliana, cotyledons and leaves synthesize indole-3-acetic acid (IAA) from tryptophan through indole-3-pyruvic acid (3-IPA) in response to vegetational shade. This newly synthesized auxin moves to the hypocotyl where it induces elongation of hypocotyl cells. Here we show that loss of function of VAS2 (IAA-amido synthetase Gretchen Hagen 3 (GH3).17) leads to increases in free IAA at the expense of IAA-Glu (IAA glutamate) in the hypocotyl epidermis. This active IAA elicits shade- and high temperature-induced hypocotyl elongation largely independently of 3-IPA-mediated IAA biosynthesis in cotyledons. Our results reveal an unexpected capacity of local auxin metabolism to modulate the homeostasis and spatial distribution of free auxin in specialized organs such as hypocotyls in response to shade and high temperature. PMID- 27249565 TI - Vascular-mediated signalling involved in early phosphate stress response in plants. AB - Depletion of finite global rock phosphate (Pi) reserves will impose major limitations on future agricultural productivity and food security. Hence, modern breeding programmes seek to develop Pi-efficient crops with sustainable yields under reduced Pi fertilizer inputs. In this regard, although the long-term responses of plants to Pi stress are well documented, the early signalling events have yet to be elucidated. Here, we show plant tissue-specific responses to early Pi stress at the transcription level and a predominant role of the plant vascular system in this process. Specifically, imposition of Pi stress induces rapid and major changes in the mRNA population in the phloem translocation stream, and grafting studies have revealed that many hundreds of phloem-mobile mRNAs are delivered to specific sink tissues. We propose that the shoot vascular system acts as the site of root-derived Pi stress perception, and the phloem serves to deliver a cascade of signals to various sinks, presumably to coordinate whole plant Pi homeostasis. PMID- 27249567 TI - Multiple domestications of Asian rice. PMID- 27249566 TI - Photodamage of iron-sulphur clusters in photosystem I induces non-photochemical energy dissipation. AB - Photosystem I (PSI) uses light energy and electrons supplied by photosystem II (PSII) to reduce NADP(+) to NADPH. PSI is very tolerant of excess light but extremely sensitive to excess electrons from PSII. It has been assumed that PSI is protected from photoinhibition by strict control of the intersystem electron transfer chain (ETC). Here we demonstrate that the iron-sulphur (FeS) clusters of PSI are more sensitive to high light stress than previously anticipated, but PSI with damaged FeS clusters still functions as a non-photochemical photoprotective energy quencher (PSI-NPQ). Upon photoinhibition of PSI, the highly reduced ETC further triggers thylakoid phosphorylation-based mechanisms that increase energy flow towards PSI. It is concluded that the sensitivity of FeS clusters provides an additional photoprotective mechanism that is able to downregulate PSII, based on PSI quenching and protein phosphorylation. PMID- 27249568 TI - Limited Phosphate: Mobile RNAs convey the message. PMID- 27249569 TI - Mobile small RNAs: Sperm-companion communication. PMID- 27249570 TI - Genomics: Decoding the ancestors of peanut. PMID- 27249571 TI - Auxin conjugation: Growing out of the shade. PMID- 27249572 TI - Re-igniting the green revolution with wild crops. PMID- 27249573 TI - Human evolution: Chewing the fat. PMID- 27249574 TI - Immunity: Decoys everywhere. PMID- 27249575 TI - Archaeobotany: Millet on the move. PMID- 27249576 TI - Photosynthesis: Compartment control. PMID- 27249577 TI - Learning from the past. PMID- 27249578 TI - Regulation of preparation courses for the Situational Judgement Test. PMID- 27249579 TI - Geometrical assembly of ultrastable protein templates for nanomaterials. AB - The fabrication of nanoscale devices requires architectural templates on which to position functional molecules in complex arrangements. Protein scaffolds are particularly promising templates for nanomaterials due to inherent molecular recognition and self-assembly capabilities combined with genetically encoded functionalities. However, difficulties in engineering protein quaternary structure into stable and well-ordered shapes have hampered progress. Here we report the development of an ultrastable biomolecular construction kit for the assembly of filamentous proteins into geometrically defined templates of controllable size and symmetry. The strategy combines redesign of protein-protein interaction specificity with the creation of tunable connector proteins that govern the assembly and projection angles of the filaments. The functionality of these nanoarchitectures is illustrated by incorporation of nanoparticles at specific locations and orientations to create hybrid materials such as conductive nanowires. These new structural components facilitate the manufacturing of nanomaterials with diverse shapes and functional properties over a wide range of processing conditions. PMID- 27249580 TI - Secondary Changes After Injury and Temperature. PMID- 27249582 TI - Re-emergence of scarlet fever: old players return? PMID- 27249585 TI - Three worlds of health technology assessment: explaining patterns of diffusion of HTA agencies in Europe - CORRIGENDUM. PMID- 27249581 TI - The Dependence of Carbohydrate-Aromatic Interaction Strengths on the Structure of the Carbohydrate. AB - Interactions between proteins and carbohydrates are ubiquitous in biology. Therefore, understanding the factors that determine their affinity and selectivity are correspondingly important. Herein, we have determined the relative strengths of intramolecular interactions between a series of monosaccharides and an aromatic ring close to the glycosylation site in an N glycoprotein host. We employed the enhanced aromatic sequon, a structural motif found in the reverse turns of some N-glycoproteins, to facilitate face-to-face monosaccharide-aromatic interactions. A protein host was used because the dependence of the folding energetics on the identity of the monosaccharide can be accurately measured to assess the strength of the carbohydrate-aromatic interaction. Our data demonstrate that the carbohydrate-aromatic interaction strengths are moderately affected by changes in the stereochemistry and identity of the substituents on the pyranose rings of the sugars. Galactose seems to make the weakest and allose the strongest sugar-aromatic interactions, with glucose, N acetylglucosamine (GlcNAc) and mannose in between. The NMR solution structures of several of the monosaccharide-containing N-glycoproteins were solved to further understand the origins of the similarities and differences between the monosaccharide-aromatic interaction energies. Peracetylation of the monosaccharides substantially increases the strength of the sugar-aromatic interaction in the context of our N-glycoprotein host. Finally, we discuss our results in light of recent literature regarding the contribution of electrostatics to CH-pi interactions and speculate on what our observations imply about the absolute conservation of GlcNAc as the monosaccharide through which N linked glycans are attached to glycoproteins in eukaryotes. PMID- 27249584 TI - The cardiac electrogenic sodium/bicarbonate cotransporter (NBCe1) is activated by aldosterone through the G protein-coupled receptor 30 (GPR 30). AB - The sodium/bicarbonate cotransporter (NBC) transports extracellular Na+ and HCO3- into the cytoplasm upon intracellular acidosis, restoring the acidic pHi to near neutral values. Two different NBC isoforms have been described in the heart, the electroneutral NBCn1 (1Na+:1HCO3-) and the electrogenic NBCe1 (1Na+:2HCO3-). Certain non-genomic effects of aldosterone (Ald) were due to an orphan G protein couple receptor 30 (GPR30). We have recently demonstrated that Ald activates GPR30 in adult rat ventricular myocytes, which transactivates the epidermal growth factor receptor (EGFR) and in turn triggers a reactive oxygen species (ROS)- and PI3K/AKT-dependent pathway, leading to the stimulation of NBC. The aim of this study was to investigate the NBC isoform involved in the Ald/GPR30 induced NBC activation. Using specific NBCe1 inhibitory antibodies (a-L3) we demonstrated that Ald does not affect NBCn1 activity. Ald was able to increase NBCe1 activity recorded in isolation. Using immunofluorescence and confocal microscopy analysis we showed in this work that both NBCe1 and GPR30 are localized in t-tubules. In conclusion, we have demonstrated that NBCe1 is the NBC isoform activated by Ald in the heart. PMID- 27249586 TI - Patient satisfaction as an excellent track record in nonsurgical rejuvenation procedures. AB - OBJECTIVE: Patient satisfaction is the goal of most aesthetic procedures. The aim of this study is to analyse nonsurgical rejuvenation procedures in a private practice setting, over a period of 10 years, evaluating patients' compliance, satisfaction and maintenance of a good fiduciary link with the medical operator. PATIENTS AND METHODS: A retrospective study was performed on 429 patients who received nonsurgical rejuvenation procedures. Four types of treatments were considered: Botulinum toxin type A injections, Hyaluronic acid or Poly-L-lactic acid injections, and a combination therapy. The outcome analyzed included a number of patients for each treatment for each year, the treatment time interval, the number of treatments for each patient, the number of treatments according to facial sub site and the "degree of satisfaction". RESULTS: The most required treatment was combination therapy (36.8% of patients). The mean time and the median time of permanency in the study were respectively 19 and 6 months. After 18 months, which is the time that we considered to attest a good "degree of satisfaction", 55% of patients were still in the study. Patients with only one treatment were excluded. CONCLUSIONS: The study findings support evidence of a more recently described increase in popularity in minimally invasive aesthetic procedures, of which combination therapy has the best performances with a good degree of satisfaction. PMID- 27249587 TI - An evaluation of fecal incontinence in women with urinary incontinence. AB - OBJECTIVE: To investigate the occurrence of and risk factors for fecal and/or gas incontinence in female patients having urinary incontinence. PATIENTS AND METHODS: 741 consecutive adult female patients presenting with urinary incontinence alone (group 1, n = 700) or urinary incontinence with fecal and/or gas incontinence (group 2, n = 41) were enrolled into the study. As potential risk factors for fecal and/or gas incontinence in this population, the following variables were investigated: age, body mass index, type of urinary incontinence, childbirth history, menopausal symptoms, history of pelvic surgery, neurological disease, diabetes mellitus, tobacco use, constipation, cystocele, rectocele. Quality of life was assessed with the Urogenital Distress Inventory-Short Form (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7). RESULTS: Of the women having urinary incontinence, 5.5% also had fecal and/or gas incontinence. Associated risk factors were history of difficult delivery, postmenopausal symptoms, history of pelvic surgery and constipation. Fecal and/or gas incontinence was also associated with a lower quality of life in terms of both questionnaires. CONCLUSIONS: Women have urinary incontinence may have also fecal and/ or gas incontinence. Particularly if they have chronic constipation, postmenopausal symptoms or history of difficult delivery or pelvic surgery they must be evaluated for this additional symptom. So we can treat these patients appropriately and increase their quality of life. PMID- 27249588 TI - Analysis of nasal cavity morphology and nasolabial development of the normal Han ethnic people under age of 12. AB - OBJECTIVE: This study aims to establish the three-dimensional (3D) reconstruction model of nasal cavity for China's Han ethnic population (0-12 years) by laser scanning and photogrammetry, and thus to elucidate the developmental mechanism of nasal cavity morphology and nasolabial region. PATIENTS AND METHODS: A total of 260 normal people of the Han ethnic aged 0-12 were recruited as subjects, among whom 60 were scanned for nasal cavity morphology in order to get reconstructed models with the computer engineering software. Photogrammetry was performed for the remaining 200 subjects to measure the 7 parameters that reflect vertically or horizontally the anatomical features of the nasolabial region. RESULTS: The interior morphology of nasal cavity was accurately established by 3D laser scanning and photogrammetry with the optimal morphology of nasal cavity simulated through 3D reconstruction. Development of nasal cavity and nasolabial region was also analyzed. CONCLUSIONS: The 3D laser scanning analysis is the ideal method to analyze the interior morphology of nasal cavity by reconstructing the normal interior morphology of nasal cavity and quantitatively analyze the change of nasal cavity morphology with age. Photogrammetry can be applied to conduct the morphological measurement for the nasolabial region and, thus, assessing the development of the nasolabial region with age, which provides information for choosing the timing and options of surgery in treating harelip and nasal deformity. PMID- 27249589 TI - Altered platelet morphological parameters in patients with retinal vein occlusion. AB - OBJECTIVE: The purpose of this work was to investigate whether platelet morphology or functions are altered in retinal vein occlusion (RVO) patients. PATIENTS AND METHODS: Eighty-three patients with a RVO and eighty-five healthy subjects were included in this prospective study. RVO was diagnosed by ophthalmic fundus examination, and complete ophthalmic evaluations of both eyes were performed. The platelet large cell ratio (PLCR), platelet distribution width (PDW), mean platelet volume (MPV), platelet crit (PCT), and platelet count were determined for each participant. RESULTS: The MPV, PDW and PLCR were significantly higher in the RVO group than in the control group (MPV: 8.26 +/- 1.22 fL vs. 7.41 +/- 0.69 fL, respectively, p = 0.006; PDW: 13.43 +/- 1.75% vs. 12.19 +/- 1.51%, respectively, p = 0.0022; and PLCR: 30.62 +/- 4.65% vs. 28.59 +/ 4.18%, respectively, p = 0.003). There were no significant differences in the PCT or platelet count between the two groups (253.76 +/- 70.87 x 103/ul vs. 248.96 +/- 62.44 x 103/ul, respectively p > 0.05; and PCT: 0.24 +/- 0.07 % vs. 0.27 +/- 0.06%, respectively, p > 0.05). CONCLUSIONS: We observed that the platelets RVO patients exhibit morphological evidence of hyperreactivity (e.g., a higher MPV, PDW and PLCR). Also, larger platelets are hemostatically more active than small ones and an increased proportion of large platelets is a risk factor for developing RVO. PMID- 27249590 TI - Serum and follicular fluid irisin levels in poor and high responder women undergoing IVF/ICSI. AB - OBJECTIVE: We examined the follicular fluid (FF) and serum levels of irisin in high and poor responders undergoing IVF/ICSI to test whether irisin has a role in the metabolic regulation of energy homeostasis in growing follicle. PATIENTS AND METHODS: Twenty infertile women with PCOS and 20 poor responder participants undergoing controlled ovarian stimulation (COS) with GnRH antagonist protocol for IVF/ICSI treatment were allocated. Blood was obtained at the time of oocyte retrieval. The follicular fluid content of mature follicles was collected from both high and poor responder women. Irisin levels were measured by using EIA. RESULTS: There was no significant difference between serum and FF-irisin levels in women with PCOS. (11.18 +/- 5.14 ug/mL vs. 11.06 +/- 4.93 ug/mL, p < 0.96). In contrast, serum levels of irisin in poor responders were significantly higher than in the FF-irisin levels (13.13 +/- 4.27 ug/mL vs. 10.09 +/- 4.14 ug/mL, p < 0.01). FF-irisin levels of PCOS subjects were positively and significantly correlated with serum levels of irisin (r: 0.81, p < 0.00). Serum irisin was positively associated with serum levels of total testosterone but was negatively associated with HOMA-IR in the overall patient population. FF-irisin levels were also noted to be negatively correlated with HOMA-IR. Although there is no correlation between serum irisin and AMH levels, FF irisin levels were negatively correlated with serum AMH levels in PCOS subjects. Contrary to PCOS group there were no significant correlation between serum and FF-irisin levels in poor responder group (r: 0.21; p < 0.35). CONCLUSIONS: The present study is the first attempt to explore the role of irisin in oocyte development by measuring FF and serum levels of this molecules in patients with poor and high responders undergoing IVF/ICSI. PMID- 27249591 TI - Comparison of the superb microvascular imaging technique and the color Doppler techniques for evaluating children's testicular blood flow. AB - OBJECTIVE: We have compared conventional Color Doppler (CD) and Power Doppler (PD) techniques, which are used for evaluating the testicular blood flow in small children, and the Superb Microvascular Imaging (SMI), which is a new technique. We have also investigated their contributions to testicular evaluations. PATIENTS AND METHODS: We evaluated blood flow in testicles using a grading system with CD, PD and SMI techniques. We determined the average duration of the three techniques. RESULTS: There was a statistically significant difference between the SMI and CD techniques for all patients (p < 0.001, p = 0.001). When we compared the PD and SMI, either as much or more vascular information was obtained (p = 0.106). There was a statistically significant difference between the application durations of the tests (p < 0.05). CONCLUSIONS: Superb Microvascular Imaging yields more detailed vascular information in blood flow in testicles in small children, than either CD or PD. Furthermore, this technique decreases the duration of the examination at a significant level. Superb Microvascular Imaging may represent an alternative method that can be used safely for evaluating blood flow in the testicles of small children. Additional studies may increase the reliability of SMI. PMID- 27249592 TI - Analysis of contrast-enhanced ultrasound (CEUS) and pathological images of hepatic alveolar echinococcosis (HAE) lesions. AB - OBJECTIVE: Contrast-Enhanced Ultrasound (CEUS) has been introduced as a promising imaging technique for diagnosis of hepatic alveolar echinococcosis (HAE). But the correlation between the image features and the underlying complex pathology of HAE has not been fully understood. In this study, we reviewed CEUS and pathological images of 31 lesions in 24 patients with HAE from Aba Tibetan Qiang Autonomous Prefecture, an epidemic area in China. MATERIALS AND METHODS: 24 patients who received CEUS examination for suspicion of HAE and with pathologically confirmed HAE were retrospectively reviewed. Parasitic lesions obtained from surgery were sectioned and stained with hematoxylin and eosin (HE). RESULTS: US examination showed that the 12 lesions were hypoechoic and 19 lesions were hyperechoic. The hypoechoic images of HAE quite resemble the images of hepatocellular carcinoma and hemangioma. For the CEUS images of lesions >=3 cm, 9 lesions (9/25, 36%) were hypoechoic with mixed content without circular rim enhancement; 16 lesions (16/25, 64%) had circular rim enhancement. All the lesions < 3 cm (n=6) were with circular rim enhancement and non-enhancement internal area. Pathological examination showed that the cysts are surrounded by an inner necrotic zone and peripheral granulomatous and fibrous tissues. CONCLUSIONS: CEUS images of large HAE lesions are more complex than that of the small lesions. Large HAE lesions can be hypoechoic with mixed content with or without circular rim enhancement, and no internal area enhancement with circular rim enhancement. The small lesions are more likely to show circular rim enhancement and non-enhancement internal area. PMID- 27249593 TI - MEK inhibitor CI-1040 induces apoptosis in acute myeloid leukemia cells in vitro. AB - OBJECTIVE: MEK1/2 (mitogen-activated protein kinase 1 and 2)/ERK1/2 (extracellular signal-regulated kinase 1 and 2) is important transducers of external signals for cell growth, survival, and apoptosis in acute myeloid leukemia cells (AML). In this study, we analyzed the effect of MEK inhibitor CI 1040 on the survival of AML cells. MATERIALS AND METHODS: Using ELISA and MTT we studied the cytotoxic effects of CI-1040 on AML U-937 cells. We studied the changes induced by CI-1040 on PUMA and p53 expression in U-937 cells by Western blotting assay. Moreover, we analyzed the cytotoxic effect of CI-1040 in U-937 cells with deleted PUMA, wt-p53 by wt-p53 siRNA and PUMA siRNA transfection. RESULTS: CI-1040 induced apoptosis and inhibited proliferation in U-937 cells in a dose and time-dependent manner. CI-1040 induced a significant increase in PUMA mRNA and protein levels. Importantly, we show that knockdown of PUMA by PUMA siRNA transfection inhibited CI-1040-induced apoptosis and proliferation inhibition in U-937 cells. Moreover, CI-1040 induced apoptosis and proliferation inhibition was irrespective of wt-P53 status. CONCLUSIONS: These results demonstrate that CI-1040 induce apoptosis of U-937 cells and might be a new therapeutic option for the treatment of AML. PMID- 27249594 TI - Expression of LRIG1 in pituitary tumor and its clinical significance. AB - OBJECTIVE: To analyze the expression of leucine-rich and immunoglobulin-like domain gene1 (LRIG1) in pituitary tumor and its clinical significance. PATIENTS AND METHODS: Patients were divided into two groups: hypophysoma group (n = 80) and normal group (normal brain tissue, n = 30). The immune tissue chemical streptavidin avidin-peroxidase was applied to detect the expression of LRIG1 of both groups and to analyze its relationship with the patients' prognosis. RESULTS: The positive expression rate of LRIG1 in normal brain tissues was significantly higher than that in pituitary adenomas (100% vs. 53.8%) (p < 0.05). The positive expression rate of LRIG1 in pituitary tumors was not significantly related to age and gender, the difference was not statistically significant (p > 0.05). The positive expression rate of LRIGl in non-invasive pituitary adenomas was higher than that in invasive pituitary tumors (68.4% vs. 21.7%), the difference was statistically significant (p < 0.05). Cox multivariate survival analysis showed that LRIG1 can be used as an independent factor for prognosis evaluation. Meier survival analysis showed that the LRIG1 and pituitary tumor types were significantly associated with the prognosis of patients (p < 0.05). CONCLUSIONS: LRIG1 was involved in the occurrence and development of pituitary tumor, the expression of LRIG1 can be used as an indicator for prognosis evaluation, and low expression indicated a poor prognosis. PMID- 27249595 TI - Serum human epididymis protein 4 vs. carbohydrate antigen 125 and their combination for endometrial cancer diagnosis: a meta-analysis. AB - OBJECTIVE: Cancer antigen 125 (CA125) and Human epididymis protein 4 (HE4) appear to be promising predictors for endometrial cancer (EC). However, conflicting results exist in the diagnostic performance comparison among CA125 and HE4. MATERIALS AND METHODS: A systematic review was conducted using PubMed, EMBASE and other databases till December 2015. All studies included were closely assessed with the QUADAS. Diagnostic value of HE4, CA125 and HE4+CA125 was systematically evaluated, and comparison among the predictive performances of HE4, CA125 were conducted. Sensitivity, specificity, DOR (diagnostic odds ratio), and area under the SROC curve were summarized with a random model. Meta-regression was used to explore the heterogeneity. RESULTS: 8 studies including 1832 cases (1129 in the study group and 703 in the control group) were included in our meta-analysis. Mean estimates of HE4 and their 95% CIs were: sensitivity 0.53 (95% CI: 0.50 0.56), specificity 0.91 (95% CI: 0.89-0.93), DOR 17.01 (95% CI: 7.88-36.72). The area under the SROC curve of HE4 in the diagnosis of EC was 0.77. However, CA125 had lower sensitivity, specificity, DOR, and the area under the SROC in diagnosis of EC with sensitivity 0.26 (95% CI: 0.24-0.29), specificity 0.81 (95% CI: 0.78 0.84), DOR 2.61 (95% CI: 0.92-7.41), and the area under the SROC 0.37. In patients with EC diagnosed by HE4+CA125, the overall sensitivity was 0.58 (95% CI: 0.54-0.62) and a specificity of 0.92 (95% CI: 0.89-0.94) in predicting EC. DOR and the area under the SROC curve of HE4+CA125 for diagnosis of EC were 21.86 (95% CI: 11.08-43.15) and 0.83 respectively, which showed a higher level of diagnostic accuracy than HE4 alone. CONCLUSIONS: HE4 is helpful for distinguishing EC from healthy and benign disease. CA125 is not better than HE4 either for EC diagnosis. HE4+CA125 is promising a predictor of EC to replace He4, but its utilization requires further exploration. PMID- 27249596 TI - Influence of body weight changes on survival in patients undergoing chemotherapy for epithelial ovarian cancer. AB - OBJECTIVE: Epithelial ovarian cancer is a highly fatal gynecologic malignancy with a poor prognosis. Therefore, identification of new modifiable prognostic factors is important. Due to the fact that the effect of body weight changes during chemotherapy for EOC is still not very well known we aimed to describe, considering evidence, role of body weight changes in relation to survival. MATERIALS AND METHODS: Between October 2014 and August 2015 we systematically searched the following databases: Medline, Scopus, Web of Science and EMBASE to identify the studies describing the influence of body weight changes on survival in patients undergoing chemotherapy for EOC. RESULTS: We identified 601 potentially relevant publications, however finally only one article was included for data extraction and analysis. The overall survival in the selected paper was significantly associated with body weight changes during the first-line chemotherapy. Nevertheless, no influence on progression free survival was found. CONCLUSIONS: The analyzed data provides initial evidence, showing poorer overall survival associated with body weight loss and improved overall survival associated with body weight gain during primary chemotherapy for epithelial ovarian cancer. Prospective and retrospective trials are an urgent calling to confirm this conclusion. PMID- 27249597 TI - Expression and clinical implication of Beclin1, HMGB1, p62, survivin, BRCA1 and ERCC1 in epithelial ovarian tumor tissues. AB - OBJECTIVE: The aim of the present study is to investigate the differential expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 protein in epithelial ovarian cancer (EOC) and to evaluate the relationship between autophagy and platinum resistance of EOC patients during platinum-based chemotherapy with the protein expression. PATIENTS AND METHODS: Expression of Beclin1, HMGB1, p62, survivin, ERCC1 and BRCA1 were detected with immunohistochemistry in 60 patients, including 39 with epithelial ovarian cancer (EOC), 13 benign epithelial ovarian tumor tissue (BET) and 8 borderline ovarian tumor tissue. RESULTS: Beclin, p62 and ERCC1 expression was significantly higher in the EOC than the BET (p<0.05). No statistical significance was detected with HMGB1 or survivin expression among BET, borderline tumor and EOC (p>0.05). BRCA1 expression was lower in EOC than BET (p<0.05). The expression of Beclin, p62 and survivin significantly correlated with FIGO stage (p<0.05), while the expression of HMGB1 correlated with pathological type. For platinum-sensitive EOC patients, positive expression of Beclin1 and BRCA1 was lower, and positive P62 expression was higher than in platinum-resistant patients (p<0.05). BRCA1 expression was negatively correlated with Beclin1 and p62 expression (p<0.05). CONCLUSIONS: Inhibition of expression of beclin1 may suppress autophagy to enhance the efficiency of platinum-sensitive ovarian cancer. HMGB1, survivin and p62 are implicated in the development of ovarian cancer. ERCC1 might be a potential predictive marker for neoadjuvant treatment in the early stage of ovarian cancer, and BRCA1, Beclin1 and p62 as a biomarker to predict platinum resistance and prognosis of epithelial ovarian cancer. PMID- 27249598 TI - MiR-181a upregulation is associated with epithelial-to-mesenchymal transition (EMT) and multidrug resistance (MDR) of ovarian cancer cells. AB - OBJECTIVE: Elevated miR-181a is associated with the transition of ovarian tissues from normal into a cancerous state. However, its regulative effect on multidrug resistance (MDR) of ovarian cancer is not quite clear. Therefore, this study aimed to investigate its regulative effects on epithelial-to-mesenchymal transition (EMT) and MDR in ovarian cancer. MATERIALS AND METHODS: The expression profile of miR-181a in normal and ovarian cancer tissues was firstly quantified using qRT-PCR analysis. Then, human ovarian cancer cell line SKOV3 were transfected for miR-181a overexpression and the paclitaxel-resistant variant SKOV3/PTX cells were transfected for miR-181a knockdown. The effect of miR-181a overexpression/knockdown on EMT and PTX sensitivity were studied. RESULTS: MiR 181a level in chemoresistant (CR) cancer tissues were significantly higher than in chemosensitive (CS) cancer tissues and in normal tissue. SKOV3/PTX cells had significantly higher expression of miR-181a and N-cadherin than SKOV3 cells. SKOV3 cells had decreased E-cadherin expression and increased N-cadherin expression after enforced miR-181a expression, while SKOV3/PTX cells had increased E-cadherin expression and decreased N-cadherin expression after miR 181a knockdown. SKOV3 cells had increased P-gp expression after enforced miR-181a expression. Following MTT assay and flow cytometry analysis both confirmed that miR-181a overexpression decreased the PTX sensitivity of SKOV3 cells and while miR-181a inhibition increased the sensitivity of SKOV3/PTX cells. CONCLUSIONS: MiR-181a is an important oncomiR significantly increased in chemoresistant ovarian cancer. Its upregulation is associated with increased level of EMT and decreased cell apoptosis induced by PTX treatment. PMID- 27249599 TI - MiR-370 promotes cell death of liver cancer cells by Akt/FoxO3a signalling pathway. AB - OBJECTIVE: MicroRNAs have emerged as key regulators in cancer cell biology. In the present study, we investigate the role and the involving mechanism of miR-370 in the progression of liver cancers. MATERIALS AND METHODS: MiR-370 levels were detected by real-time PCR assay. Cell proliferation of HepG2, MHCC-97H and SMMC 7721 was determined by MTT assay. PI staining was detected by FACS analysis. Colony formation was used to test liver cancer cell growth. FoxO3a and Akt expression was determined by western blotting analysis. RESULTS: MiR-370 level was significantly down-regulated in liver cancer cells. Functional analysis revealed that miR-370 mimics suppressed cell proliferation of liver cancer cells, while transfection with miR-370 inhibitor increased cell proliferation of liver cancer cells. Moreover, miR-370 mimics induced cell death of HepG2. Furthermore, Western blotting analysis results demonstrated that miR-370 inhibited the proliferation of liver cancer cells by activating FoxO3a. CONCLUSIONS: MiR-370 inhibited cell proliferation of liver cancer cells by PI3K/Akt signaling pathway. It worked as a tumor suppressor to suppress the progression of human liver cancers. PMID- 27249600 TI - MiR-183 modulates multi-drug resistance in hepatocellular cancer (HCC) cells via miR-183-IDH2/SOCS6-HIF-1alpha feedback loop. AB - OBJECTIVE: MiR-183 acts as an oncomiR and is usually upregulated in hepatocellular cancer (HCC). This study aims to study the association between miR 183 dysregulation and multi-drug resistance (MDR). Also, how it is dysregulated in HCC cells was investigated. MATERIALS AND METHODS: The association between miR 183 and HIF-1alpha in HCC cell line BEL-7402 and the multidrug-resistant variant BEL-7402/5-fluorouracil (BEL-7402/5-FU) were studied using qRT-PCR and Western blot analysis. The mediators involved in feedback regulation between miR-183 and HIF-1alpha were further studied. Then, the effect of the miR-183-SOCS6 axis on IC50 of BEL-7402/5-FU cells to 5-FU were investigated by MTT assay. RESULTS: The expression of miR-183 and HIF-1alpha are positively correlated in BEL-7402 and BEL-7402/5-FU cells. IDH2 knockdown resulted in significantly increased HIF 1alpha expression in both BEL-7402 and BEL-7402/5-FU cells. Knockdown of SOCS6 had similar but stronger effect as miR-183 in promoting MRP2, P-gp, p-STAT3 and HIF-1alpha expression in BEL-7402 cells, while SOCS6 overexpression also showed similar but stronger effect as miR-183 inhibition in reducing MRP2, P-gp, p-STAT3 and HIF-1alpha levels in BEL-7402/5-FU cells. Both SOCS6 overexpression and miR 183 knockdown significantly increased the sensitivity of BEL-7402/5-FU cells to 5 FU. MiR-183 overexpression partly abrogated the effect of SOCS6 in enhancing 5-FU sensitivity. CONCLUSIONS: Both HIF-1alpha-miR-183-IDH2-HIF-1alpha and HIF-1alpha miR-183-SOCS6-p-STAT3-HIF-1alpha feedback loops are involved in miR-183 upregulation in HCC cells. MiR-183 can modulate MDR of HCC cells at least partly through suppressing SOCS6. PMID- 27249601 TI - Upregulated STAT3 and RhoA signaling in colorectal cancer (CRC) regulate the invasion and migration of CRC cells. AB - OBJECTIVE: We aimed to reveal the expression and activation of signal transducers and activators of transcription 3 (STAT3) and RhoA/Rho-associated coiled-coil forming kinase 1 (ROCK1) signaling in CRC tissues, and to investigate the regulatory role of STAT3 and RhoA signaling in the invasion and migration of colorectal cancer cells. MATERIALS AND METHODS: We examined the expression of STAT3, RhoA and ROCK1 in CRC tissues with real-time PCR and Western blotting methods. And then we examined the interaction between STAT3 and RhoA/ROCK1 signaling in CRC HT-29 cells with gain-of-function and loss-of-function strategies. In addition, we determined the regulation by STAT3 and RhoA/ROCK1 on the invasion and migration of CRC HT-29 cells. RESULTS: Our study demonstrated a significant upregulation of RhoA and ROCK1 expression and STAT3-Y705 phosphorylation in 32 CRC specimens, compared to the 17 normal CRC tissues. Further study demonstrated there was a coordination between STAT3 and RhoA/Rock signaling in the HT-29 cells. Moreover, STAT3 knockdown or RhoA knockdown significantly repressed the migration and invasion in HT-29 cells and vice versa. CONCLUSIONS: STAT3 and RhoA signaling regulate the invasion and migration of CRC cells, implying the orchestrated and oncogenic roles of STAT3 and RhoA/ROCK1 signaling in CRC. PMID- 27249602 TI - STMN1 in colon cancer: expression and prognosis in Chinese patients. AB - OBJECTIVE: To study the stathmin (STMN1) expression in colorectal cancer and tumor-adjacent normal tissue and discuss its prognostic significance in colon cancer. PATIENTS AND METHODS: STMN1 was tested with qRT-PCR in 30 samples of fresh colon cancer tissue and tumor-adjacent issue, and with immunohistochemical SP method in 105 samples of fresh colon cancer tissue and tumor-adjacent issue to analyze the association between its expression and clinical pathological parameters. Clinical data was combined to study the relationship between STMN1 expression and 5-year survival rate. Univariate analysis and Cox multivariate regression were performed to study the correlation between STMN1 expression and prognosis. RESULTS: The mRNA and protein level of STMN1 were significantly higher in colon cancer samples than tumor-adjacent normal tissues (p<0.05). STMN1 expression was independent of patient age, gender or location, but significantly related to lymph node metastasis and TNM staging (p<0.05). Survival analysis by Kaplan-Meier method showed that STMN1 expression was significantly related with the survival of colon cancer patients. The median survival time of STMN1-positive patients (37.5 months) was significantly shorter than STMN1-negative patients (57.1 months, p<0.05). Cox multivariate regression indicated that STMN1 is independent prognostic factors predicting the development, invasion and metastasis of colon cancer (p<0.05). CONCLUSIONS: STMN1 overexpression in colon cancer is independently associated with improved survival and significantly related to the development of the disease. Our findings suggest that presence of a STMN1-prognosis interaction that potentially determines clinical outcome. PMID- 27249603 TI - Cancer stem cell targets - a review. AB - The varied therapeutic approaches like radiotherapy, chemotherapy, surgery, etc. primarily aimed to target cancer cells specifically. Despite these efforts, they are not completely successful in eliminating this deadly pathological state. These failures ultimately lead to cancer reoccurrence, which is again, another burning problem associated with cancer. The prime reason for the above observation has been found to be the development of resistance by cancer cells towards cancer drugs or cancer-initiating cells (cancer stem cells) remain unaffected by existing treatment procedures. Recent research has evolved two drugs, salinomycin and apoptin, that hold great potential for the future of cancer treatment not only for restricting malignancy, but also in preventing tumor recurrence. The present review article will put light on these new upcoming cancer stem cell targeting agents. PMID- 27249604 TI - Screening of anti-mitochondrial antibody subtype M2 in residents at least 18 years of age in an urban district of Shanghai, China. AB - OBJECTIVE: To analyze the prevalence of anti-mitochondrial antibody subtype M2 (AMA-M2) in a healthy population, and characterize the clinical features and risk factors of primary biliary cirrhosis (PBC). PATIENTS AND METHODS: AMA-M2 was screened by enzyme-linked immunosorbent assay (ELISA) in 19012 residents who received health checkup in Xuhui District of Shanghai. Other relevant liver biochemical markers and responses to questionnaires were reviewed and analyzed. RESULTS: Total 133 residents (about 0.73% of the 19012 residents) were detected AMA-M2, including 33 males (0.40%) and 100 females (0.94%). PBC was confirmed in 25 residents. Pollution and household smoking were found to be related to PBC. In addition, the prevalence of M2 antibody was found significantly higher in the residents living near viaducts, especially the intersection region of multiple viaducts, than those who lives in other regions. CONCLUSIONS: Although the incidence of PBC is low, it is not a rare disease, and PBC may be associated with the living environment and genetic factors. PMID- 27249605 TI - Relationship between HBV DNA load and levels of serum HBsAg in patients with chronic hepatitis B. AB - OBJECTIVE: This study aims to investigate the relationship between HBV DNA load and levels of serum HBsAg in patients with chronic hepatitis B (CHB). PATIENTS AND METHODS: Between April 20013 and July 2015, serum samples were collected from 124 CHB patients. Levels of serum HBsAg was determined using chemiluminescent immunoassay and HBV DNA load was measured using quantitative fluorescent RT-PCR (qPCR). Pearson's correlation analysis was performed to analyze the relationship between HBV DNA load and levels of serum HBsAg. RESULTS: Serum HBsAg levels were significantly higher in the group with HBV DNA > 1*103 copies/ml than the group with HBV DNA < 1*103 copies/ml (t=5.983, p=0.000<0.05). One hundred samples with HBV DNA > 1*103 copies/ml were further divided into three subgroups based on HBV DNA load, including group A (levels of serum HBV DNA between 1*103- 1*105 copies/ml), group B (1*105- 1*107 copies/ml) and group C (> 1*107 copies/ml). Levels of serum HBsAg increased with increasing load of HBV DNA. HBsAg levels were the highest in group C and the lowest in group A with significant differences between groups (p<0.05). Pearson's correlation analysis revealed that levels of serum HBV DNA were positively correlated with levels of serum HBsAg (r=0.657, p=0.000<0.05). CONCLUSIONS: HBV DNA load has a certain correlation with levels of serum HBsAg in CHB patients. The combination of HBV DNA load assessment and measurement of serum HBsAg levels can accurately determine HBV infection condition, help with the selection of optimal therapy and predict prognosis. PMID- 27249606 TI - Primary pulmonary MALT lymphoma - case report and literature overview. AB - OBJECTIVE: Primary pulmonary lymphomas (PPL) are rarely taken into consideration in the differential diagnosis of lung lesions. The aim of this report is to characterize the symptoms, diagnosis and treatment of primary MALT lymphoma of the lung. CASE REPORT: We present the case of a 48-year-old man who was admitted to hospital with a history of coughing, fever, fatigue and non-specific lesions on his chest X-ray. RESULTS: The patient was treated for pneumonia, but showed no improvement. A computer tomography revealed atypical lesions. After an initial examination and tests, no diagnosis could be established. A thoracotomy with an open lung biopsy was performed and MALT lymphoma was finally diagnosed. The patient underwent chemotherapy and showed a significant improvement. CONCLUSIONS: Primary MALT lymphoma is a rare disease and its diagnosis is difficult. There is no non-invasive test that is specific enough, so a proper diagnosis can only be established by a histopathological examination. The disease has a slow and mild course and the response to treatment is satisfactory. PMID- 27249607 TI - Association between SNPs in the promoter region in cathepsin S and risk of asthma in Chinese Han population. AB - OBJECTIVE: Cathepsin S (CTSS) is a lysosomal cysteine protease and is predominantly expressed in antigen-presenting cells, which plays an important role in the allergic response. In this study, we explored the association between single nucleotide polymorphisms (SNPs) in the promotor regions in CTSS and risk of asthma. PATIENTS AND METHODS: A total of 591 cases and 621 controls were recruited for this study. Five SNPs in the CTSS were selected including rs7534124, rs16827671, rs34495036, rs3754212, and rs1136774. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed for genotyping. RESULTS: Logistic regression analysis showed that rs7534124 CT and CT + CC genotypes had significantly decreased risk of asthma (CT vs. TT, OR: 0.576, 95% CI: 0.425-0.780, p < 0.001; CT + CC vs. TT, OR: 0.638, 95% CI: 0.479-0.849, p < 0.001; respectively) compared to TT genotype. Similarly, the rs1136774 AG and AG + GG genotypes (AG vs. AA, OR: 0.581, 95% CI: 0.426-0.793, p = 0.001; AG + GG vs. AA, OR: 0.647, 95% CI: 0.483-0.867, p = 0.004, respectively) were also associated with a decreased risk of asthma. However, there was no significant association between genotypes of the remaining SNPs and the risk of asthma (p > 0.006). Moreover, the alleles in all SNPs are also not associated with the risk of asthma. CONCLUSIONS: Our study provided strong evidence that polymorphism of rs7534124 and rs1136774 in CTSS promoter may decrease the susceptibility of asthma in a Chinese Han population. PMID- 27249608 TI - Methylprednisolone combined with low-dose indomethacin treating acute fibrinous and organizing pneumonia after a surgical resection of rectal adenocarcinoma: a case report and literature review. AB - OBJECTIVE: Acute Fibrinous and Organizing Pneumonia (AFOP) is a new pathologic pattern of acute lung injury characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" in a patchy distribution. CASE REPORT: A 65 years-old female after a surgical resection of rectal adenocarcinoma presented with typical manifestations of hospital-acquired pneumonia, but she didn't respond to the anti infective therapy. After an explicit diagnosis of AFOP via percutaneous needle lung biopsy, she got an impressive improvement with a long term therapy of methylprednisolone and low-dose indomethacin. To date, a total of non-overlapped 45 individual AFOP cases and 4 single-center studies involving AFOP have been reported. The most common coexisting diseases are infections, connective tissue diseases and hematological diseases. Corticosteroids and immunosuppressants are the most common agents prescribed in AFOP. The prognosis of AFOP is unfavorable, associated with the pathologic characteristics and the clinical parameters. CONCLUSIONS: The immune system activated by infection may play an important role in the pathogenesis of AFOP. Low-dose indomethacin combined with methylprednisolone may be a new choice for AFOP treatment. PMID- 27249610 TI - Computerized dynamic pupillometry indices mirrors the heart rate variability parameters. AB - OBJECTIVE: Dynamic pupillometry (DP) is a simple, non-invasive computerized assessment of pupillary light response which provides data concerning both branches of the autonomous nervous system (ANS). Heart rate variability (HRV) analysis assess cardiac health and the ANS modulation on the heart. In this study, we aimed to evaluate the utility of DP as a predictor of cardiac autonomic activity assessed by HRV. PATIENTS AND METHODS: A total of 44 consecutive healthy subjects (mean age = 35.9 +/- 7.4 years, 24 males) were enrolled. Pupil diameters (R0, R1, R2 and R%): latency (Lc), amplitude (Ac), velocity (Vc) and duration of pupil contraction (Tc): latency (Ld), velocity (Vd) and duration of pupil dilatation (Td) were measured in DP. Time and frequency domain indices of HRV were obtained from 24-h ambulatory electrocardiographic monitoring. RESULTS: There were strong significant correlations of Vc with LF/HF (r = -0.672, p = 0.001) and a measure of HRV: RMSDD (r = 0.654, p = 0.001). R% significantly correlated with PNN50 (r = -0.432, p = 0.003) and RMSDD (r = -0.422, p = 0.004) and LF/HF (r = 0.340, p = 0.024). Vc (beta = 0.647, p = 0.011) and Ac (beta = 0.320, p = 0.013) were found as independent predictors of RMSSD. Vc (beta = 0.578, p = 0.036) was found to be only significant predictor of PNN50. Vc (beta = -0.617, p = 0.008) and R% (beta = 0.309, p = 0.038) were found to be significant predictors of LF/HF. CONCLUSIONS: Pupillary autonomic functions assessed by DP correlates with cardiac autonomic functions evaluated by HRV. Among the DP parameters analyzed, Vc was a predictor of parasympathetic indices, and R% was a predictor of sympathetic indicators of cardiac autonomic functions. PMID- 27249609 TI - Statin-treated patients with aneurysmal subarachnoid haemorrhage: a meta analysis. AB - OBJECTIVE: The cerebral vasospasm, delayed ischemic neurological deficit (DIND), mortality and poor neurological outcome induced by aneurysmal subarachnoid haemorrhage (SAH) remain the major causes of morbidity and mortality in aneurysmal SAH patients. The effects of statin-treated for aneurysmal SAH patients were not comprehensively assessed. PATIENTS AND METHODS: A systematically literature search was conducted in PubMed, EMBASE, ScienceDirect and Web of Science to identify relevant studies update to March 2015. Data were extracted and appraised independently by two authors. Moreover, fixed or random effects models were applied to calculate pooled results based on the degree of heterogeneity. RESULT: Nine RCTs and three observational studies with a total of 1957 patients met the inclusion criteria. The results showed that statin treatment was not associated with a decrease in the occurrence of DIND (RR: 0.81, 95% CI: 0.66-1.00, p = 0.05), mortality (RR: 0.90, 95% CI: 0.69-1.18, p = 0.46) and poor neurological outcome (RR: 1.02, 95% CI: 0.86-1.20, p = 0.84), nonetheless, had a potential effect on reducing the incidence of vasospasm (RR: 0.77, 95% CI: 0.66-0.89, p = 0.0006). CONCLUSIONS: This meta-analysis indicated that the use of statins decreases the occurrence of cerebral vasospasm, whereas did not support a beneficial effect of statins on the occurrence of DIND, death or poor neurological outcomes in patients with aneurysmal SAH. PMID- 27249611 TI - Malignant ventricular arrhythmias induction by programmed electrical stimulation of the right ventricular outflow tract only during type 1 Brugada ECG maximization. AB - OBJECTIVE: The role of electrophysiology study in Brugada syndrome (BS) sudden cardiac death risk stratification remains controversial and seems to depend on the phenotypic expression of the channelopathy. Ajmaline has a key role in the diagnosis of BS. We observed that programmed electrical stimulation (PES) of the right ventricular outflow tract (RVOT), only when type 1 BS ECG is unmasked by ajmaline administration, induces ventricular arrhythmias. CASE REPORT: We describe a case of ventricular fibrillation induction by PES of the RVOT when type 1 BS ECG is revealed by ajmaline, in a patient with a baseline dynamic intermittent type 1 and 2 BS ECG. CONCLUSIONS: The heterogeneous clinical presentations of BS are due to the underlying mechanisms. PES of the RVOT during positive ajmaline test maximizes the channelopathy and therefore sudden cardiac death risk-stratification in BS. PMID- 27249612 TI - The impact of laparoscopic sleeve gastrectomy on plasma obestatin and ghrelin levels. AB - OBJECTIVE: To investigate the effect of laparoscopic sleeve gastrectomy (LSG) on the levels of obestatin and ghrelin hormones and body mass index (BMI) in morbidly obese patients. PATIENTS AND METHODS: The study included 30 morbidly obese patients who had LSG. Five cc blood samples were taken from the patients preoperatively and at postoperative months 3 and 6. After serum extraction, the levels of obestatin and ghrelin hormones and the levels of fasting insulin and glucose were studied using the enzyme-linked immunosorbent assay (ELISA) method. The homeostatic model assessment of insulin resistance (HOMA-IR) score was calculated. Preoperative and postoperative 3- and 6-month BMI were calculated. Kruskal-Wallis Analysis of Variance, Bonferroni-Dunn Test, Spearman's correlation test, and Pearson's correlation test were used for statistical analysis. RESULTS: BMI of the patients were statistically significantly reduced at postoperative months 3 and 6 compared to preoperative values, and at postoperative month 3 compared to month 6 values (p < 0.001). Ghrelin values were higher at postoperative month 6 compared to the preoperative and postoperative month 3 values (p < 0.001). Obestatin values of the patients were lower at postoperative month 6 compared to the preoperative and postoperative month3 values (p < 0.001). Insulin and glucose values were statistically significantly lower at postoperative months 3 and 6 compared to preoperative values (p < 0.001), whereas there was no difference between months 3 and 6. HOMA-IR score was significantly lower at postoperative month 3 compared to preoperative values (p < 0.001). CONCLUSIONS: LSG enables effective weight loss and glucose regulation in obese patients. LSG has also effects on obestatin and ghrelin hormones, which are coded by the same gene and have opposing effects, and the associated mechanisms of which are still controversial. Obestatin produces a feeling of satiety, whereas ghrelin initiates eating by producing a feeling of hunger. The patients were observed to have increased ghrelin and reduced obestatin postoperatively due to a negative energy balance. PMID- 27249613 TI - Swimming intervention mitigates HFD-induced obesity of rats through PGC-1alpha irisin pathway. AB - OBJECTIVE: Irisin, a newly discovered myokine, can drive the browning of white adipocytes to control body weight or mitigate obesity progression through regulating energy metabolism. However, the underlying mechanisms or specific signal pathways of exercise-induced irisin on the management of obesity are still unclear. MATERIALS AND METHODS: Totally 30 rats were subjected to high fat diet (HFD) feeding for 8 weeks to establish the rat model with obesity successfully. HFD-induced obese model rats were provided with 8 weeks swimming intervention at moderate intensity for exploring the treatment of obesity through exercise intervention. In addition, another 15 rats were subjected to HFD feeding coupled with total 16 weeks swimming intervention at a moderate intensity from the beginning of the experiment, which was used for exploring the prevention of obesity through exercise intervention. Blood and gastrocnemius samples were harvested from obese rats after swimming intervention to explore its specific signal pathways through ELISA analysis and Western blotting. RESULTS: HFD feeding of rats for 8 weeks could lead to the obesity due to the disorders of lipid metabolism. Totally 8 weeks swimming intervention at moderate intensity for rats with obesity could obviously alleviate the progression of obesity and 16 weeks swimming intervention from the beginning of the experiment could significantly inhibit the development of obesity. Meanwhile, swimming intervention could result in an increased phosphorylation of AMPK and up-regulation of irisin and PGC 1alpha as the biomarkers of energy metabolism. CONCLUSION: Exercise intervention can activate PGC-1alpha-dependent irisin to induce the browning of white adipocytes, thus inhibiting or alleviating the occurrence and development of obesity. PMID- 27249614 TI - Application of Boston matrix combined with SWOT analysis on operational development and evaluations of hospital development. AB - The aim of this study is to explore the application of Boston matrix combined with SWOT analysis on operational development and evaluations of hospital departments. We selected 73 clinical and medical technology departments of our hospital from 2011 to 2013, and evaluated our hospital by Boston matrix combined with SWOT analysis according to the volume of services, medical quality, work efficiency, patients' evaluations, development capacity, operational capability, economic benefits, comprehensive evaluation of hospital achievement, innovation ability of hospital, influence of hospital, human resources of hospital, health insurance costs, etc. It was found that among clinical departments, there were 11 in Stars (22.4%), 17 in cash cow (34.7%), 15 in question marks (31.2%), 6 Dogs (12.2%), 16 in the youth stage of life cycle assessment (27.6%), 14 in the prime stage (24.1%), 12 in the stationary stage (20.7%), 9 in the aristocracy stage (15.5%) and 7 in the recession stage (12.1%). Among medical technology departments, there were 5 in Stars (20.8%), 1 in Cash cow (4.2%), 10 in question marks (41.6%), 8 Dogs (29.1%), 9 in the youth stage of life cycle assessment (37.5%), 4 in the prime stage (16.7%), 4 in the stable stage (16.7%), 1 in the aristocracy stage (4.2%) and 6 in the recession stage (25%). In conclusion, Boston matrix combined with SWOT analysis is suitable for operational development and comprehensive evaluations of hospital development, and it plays an important role in providing hospitals with development strategies. PMID- 27249615 TI - Mobile technology in health information systems - a review. AB - Mobile technology is getting involved in every sphere of life including medical health care. There has been an immense upsurge in mobile phone-based health innovations these days. The expansion of mobile phone networks and the proliferation of inexpensive mobile handsets have made the digital information and communication technology capabilities very handy for the people to exploit if for any utility including health care. The mobile phone based innovations are able to transform weak and under performing health information system into more modern and efficient information system. The present review article will enlighten all these aspects of mobile technology in health care. PMID- 27249616 TI - Sirt 1 activator attenuates the bleomycin-induced lung fibrosis in mice via inhibiting epithelial-to-mesenchymal transition (EMT). AB - OBJECTIVE: The aim of this study was to investigate the effect of resveratrol on the idiopathic bleomycin (BLM)-induced pulmonary fibrosis, which is increasingly recognized as an epithelial-to-mesenchymal transition (EMT)-associated disease. MATERIALS AND METHODS: We evaluated the effect of resveratrol on the BLM-induced fibrosis in a mouse model, via monitoring the pathological chance in mice lung, the mice body weight change and the mice death. And we also explored the regulation by BLM on (and) resveratrol on the expression and activity of Sirt 1 and on the expression of epithelial-to-mesenchymal transition (EMT)-associated markers in mice lung. RESULTS: It was demonstrated that resveratrol ameliorated the BLM-induced fibrosis-like pathological change in mice lung, inhibited BLM induced mice body weight loss and death. Moreover, resveratrol also inhibited the BLM-induced EMT-associated molecular events, such as reduced E-cadherin and elevated Collagen I and alpha-SMA. We also confirmed the amelioration by resveratrol on the BLM-mediated inhibition of Sirt 1 in expression and activity in mice lung. CONCLUSIONS: Our study confirmed the inhibitory role of resveratrol in the BLM-induced pulmonary fibrosis in a mouse model. Resveratrol ameliorated the BLM-induced pathological change of fibrosis, mice body weight loss and death. And such amelioration might be associated with the activation of Sirt 1 in mice lung. The present study implied that resveratrol might be a promising agent for effective control the pulmonary fibrosis. PMID- 27249617 TI - Study on clinical effect and immunologic mechanism of infants capillary bronchitis secondary bronchial asthma treated with bacterial lysates Broncho Vaxom. AB - OBJECTIVE: To study the clinical effects and immunologic mechanism of infant capillary bronchitis secondary bronchial asthma treated with bacterial lysates (Broncho-Vaxom OM-85BV). PATIENTS AND METHODS: Between February 2013 and February 2014, 136 infant capillary bronchitis secondary bronchial asthma cases were chosen. This research was approved by Ethics Committee in our hospital and obtained the informed consent right from patients and guardians. Patients were divided into the control group (n = 62) and the observation group (n = 74) using random number table method. Patients in the control group were treated with normal glucocorticoid atomizing inhalation, aminophylline and antibiotic treatment. In the observation group besides the abovementioned treatment, we added Broncho-Vaxom OM-85BV, qd po for 10 days continuously and quitted it for 20 days. This continued for a total of 3 months. Follow-ups were set for about one year to compare the effects. RESULTS: The onset frequency and duration of capillary bronchitis and asthma in observation group declined remarkably compared with control group and the differences were statistically significant (p < 0.05). The level of IL-17 and IL-4 in the observation group decreased significantly, whereas, the level of IL-10 and IFN- gamma increased considerably. Differences were all statistically significant (p < 0.05). Peripheral blood CD4+ T lymphocytes in the observation group patients expressed lower levels of nicotinic acetylcholine receptors alpha7 (alpha7nAChR) compared to the control group. Then difference was statistically significant (p < 0.05). CONCLUSIONS: Broncho-Vaxom OM-85BV reduced the onset of infant capillary bronchitis secondary bronchial asthma, relating to the reduced inflammation reaction. It also regulated the immunologic function of Th1/Th2, and lowered the alpha7nAChR level. PMID- 27249618 TI - Changes in cognitive function due to combined propofol and remifentanil treatment are associated with phosphorylation of Tau in the hippocampus, abnormal total water and calcium contents of the brain, and elevated serum S100beta levels. AB - OBJECTIVE: Propofol and remifentanil are commonly used combined for anaesthesia and can cause cognitive dysfunction. We hypothesized that combined treatment with these drugs would exert its effect via increased phosphorylation of Tau protein in the brain hippocampus. To address this, we assessed cognitive function and extent phosphorylation of Tau in experimental animals treated with either drug or their combination. In addition, we documented other biochemical abnormalities, such as brain total calcium and water contents, and serum levels of S100beta protein. MATERIALS AND METHODS: 60 Sprague-Dawley (SD) rats were divided into 5 groups: control, model, propofol-treated, remifentanil-treated, and combined treatment groups (12 animals per group). The Morris water maze test assessed latent periods as a measure of cognitive function in experimental animals. Tau phosphorylation was quantified by immunohistochemistry and expressed as a number of cells with positive Tau expression and as average staining area. Brain water content was assessed by measuring wet and dry brain weights, and calcium content was evaluated by the flame atomic absorption spectroscopy method. Serum S100beta levels were assessed by ELISA. RESULTS: Treatment with propofol and remifentanil markedly increased the latent period in the Morris water maze test, increased number the extent of Tau phosphorylation in the hippocampus, adversely modulated total water and calcium content in the brain, and elevated serum S100beta levels. Under all conditions, combined treatment caused more pronounced effects on the studied outcomes. CONCLUSIONS: Propofol combined with remifentanil induces a cognitive decline which is associated with Tau phosphorylation and modulation of local and systemic biochemical parameters. PMID- 27249619 TI - The effect of desflurane on postoperative olfactory memory. AB - OBJECTIVE: In this study, we investigated the effects of desflurane 6%, on olfactory memory. PATIENTS AND METHODS: This is a prospective clinical study performed with 40 patients aged 18-60 who had elective surgery and American Society of Anesthesiologists (ASA) physical status I-III. The Brief Smell Identification Test (BSIT) was used for evaluating patients' olfactory memories before and after the surgery. Patients received standard general anesthesia protocol and routine monitoring. For induction, 1.5 mg/kg of fentanyl, 2 mg/kg of propofol, and 0.5 mg/kg of rocuronium bromide were administered. Anesthesia was maintained with the inhalational of anesthetic desflurane (6%). The scores are recorded 30 minutes before the surgery and when the Aldrete Recovery Score reached 10 in the postoperative period. Preoperative and postoperative results were compared and p-values <0.05 were considered statistically significant. RESULTS: The patients' mean age was 41.1+/-12.0. Preoperative total correct answer rate to odorous substances was 92.7%, and postoperative rate was 92.1%. Percentage of the odor substance identification by the patients revealed no statistically significant difference when pre and post-operative rates have been compared (p-value >0.05). CONCLUSIONS: We have observed for the first time in the literature that general anesthesia using desflurane (6%) did not affect short term olfactory memory. Further studies will be necessary to confirm our findings with larger sample size. PMID- 27249620 TI - Does calcium dobesilate protect against intestinal ischemia-reperfusion injury induced in rats? AB - OBJECTIVE: In this study, we investigated whether the administration of calcium dobesilate (CD) affects oxidative stress markers and histopathological outcomes in a rat model of intestinal ischemia-reperfusion (IR) injury. MATERIALS AND METHODS: This study was conducted with 30 male Wistar rats. The rats were randomly assigned to three groups as follows: a sham group (n = 10), an IR group (n = 10), and an IR + CD group (n = 10). In the sham group, superior mesenteric artery (SMA) dissection alone was performed during laparotomy. In the IR group, the procedure included SMA occlusion for 60 min, followed by reperfusion for 60 min. In the IR + CD group, CD (100 mg/kg/day) was additionally given for two days before laparotomy by intragastric lavage. In all the rats, 2 ml of blood were drawn, and an ileal segment (approximately 2 cm in size) was removed to evaluate oxidative stress markers. The ileal segment removed was divided into two pieces, and one piece was reserved for histopathological evaluation. RESULTS: Compared to the other groups, both serum and tissue oxidative stress indices were lower in the IR + CD group. The decrease was due to CD increasing the total antioxidant capacity. Moreover, the histological analysis showed that CD reduced tissue injury. CONCLUSIONS: CD may exert a protective effect against intestinal IR injury by increasing antioxidant capacity. PMID- 27249621 TI - Vitamin C suppresses lipopolysaccharide-induced procoagulant response of human monocyte-derived macrophages. AB - OBJECTIVE: Although vitamin C is a strong antioxidant, the epidemiologic evidence to support its role in lowering risk of cardiovascular disease is inconsistent. In order to define the role of vitamin C in vascular pathophysiology, we have investigated the effect of vitamin C on the tissue factor (TF) and Factor VII Activating Protease (FSAP) expression induced by lipopolysaccharide (LPS) in human monocyte-derived macrophages. MATERIALS AND METHODS: Vitamin C at clinically relevant doses was tested to its ability to influence the LPS- and reactive oxygen species (ROS) - generating system of xanthine/xanthine oxidase (X/XO) NF-kB activity in human monocyte-derived macrophages. RESULTS: Vitamin C treatment prevents LPS- and ROS-induced DNA-binding activity of NF-kB in a concentration-dependent fashion. Vitamin C also inhibited the phosphorylation and proteolytic degradation of the inhibitor protein IkBa. In parallel to regulate NF kB activity, vitamin C reduced the expression of TF and FSAP, genes known to be induced by bacterial LPS and triggered the extrinsic coagulation cascade and linked thrombosis with inflammation. CONCLUSIONS: Vitamin C alters pro inflammatory and pro-coagulatory processes via inhibition of NF-kB activation and exerts beneficial antiatherogenic effects on human monocyte-derived macrophages in addition to its anti-oxidant properties. PMID- 27249622 TI - Childhood-onset systemic lupus erythematosus: early disease manifestations that the paediatrician must know. PMID- 27249623 TI - Large Annular Plaque on the Arm of a Patient With Recurrent Headaches. PMID- 27249624 TI - Exopisiod B and farylhydrazone C, two new alkaloids from the Antarctic-derived fungus Penicillium sp. HDN14-431. AB - Two new compounds, exopisiod B (1) and farylhydrazone C (2), together with two known compounds (3-4), were isolated from the Antarctic-derived fungus Penicillium sp. HDN14-431. Their structures including absolute configurations were elucidated by spectroscopic methods and TDDFT ECD calculations. The cytotoxicity and antimicrobial activities of all compounds were tested. PMID- 27249625 TI - Application of texture analysis on parametric T1 and T2 maps for detection of hepatic fibrosis. AB - PURPOSE: To assess the utility of texture analysis of T1 and T2 maps for the detection of hepatic fibrosis in a murine model of hepatic fibrosis. MATERIALS AND METHODS: Following Institutional Animal Care and Use Committee approval, a dietary model of hepatic fibrosis was used and 15 ex vivo murine livers were examined. Images were acquired using a 30 mm bore 11.7T magnetic resonance imaging (MRI) scanner with a rapid acquisition with relaxation enhancement sequence. Texture analysis was then employed, extracting texture features including histogram-based, gray-level co-occurrence matrix-based (GLCM), gray level run-length-based features (GLRL), gray-level gradient matrix (GLGM), and Laws' features. Areas under the curve (AUCs) were then calculated to determine the ability of texture features to detect hepatic fibrosis. RESULTS: Texture analysis of T1 maps identified very good to excellent discriminators of hepatic fibrosis within the histogram and GLGM categories. Histogram feature interquartile range (IQR) achieved an AUC value of 0.90 (P < 0.0001) and GLGM feature variance gradient achieved an AUC of 0.91 (P < 0.0001). Texture analysis of T2 maps identified very good to excellent discriminators of hepatic fibrosis within the histogram, GLCM, GLRL, and GLGM categories. GLGM feature kurtosis was the best discriminator of hepatic fibrosis, achieving an AUC value of 0.90 (P < 0.0001). CONCLUSION: This study demonstrates the utility of texture analysis for the detection of hepatic fibrosis when applied to T1 and T2 maps in a murine model of hepatic fibrosis and validates the potential use of this technique for the noninvasive, quantitative assessment of hepatic fibrosis. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:250-259. PMID- 27249626 TI - Witnesses stumbling down memory lane: The effects of alcohol intoxication, retention interval, and repeated interviewing. AB - Intoxicated eyewitnesses are often discredited by investigators and in court, but few studies have examined how alcohol affects witnesses' memory. The primary aim of the present study was to examine how intoxication (alcohol vs. control), retention interval (immediate vs. one week delay), and number of interviews (one vs. two interviews) affect witnesses' memory. The participants (N = 99) were randomly assigned to consume either orange juice or alcohol mixed with orange juice, and they all witnessed a filmed mock crime afterwards. The recall took place either (a) immediately and after a one week delay or (b) after a one week delay only. No main effect of alcohol was found on the quantity or quality of the witnesses' statements. Both intoxicated and sober witnesses recalled more details, and were more accurate, during immediate compared to delayed recall. For witnesses interviewed twice, an average of 30% new details were provided in the second compared to the first interview, and these were highly accurate. In sum, contrary to what one can expect, intoxicated witnesses with a low to moderate blood alcohol concentration (below 0.10%) were reliable witnesses. PMID- 27249627 TI - Human annulus progenitor cells: Analyses of this viable endogenous cell population. AB - Back pain and intervertebral disc degeneration have growing socioeconomic/health care impacts. Increasing research efforts address use of stem and progenitor cell based replacement therapies to repopulate and regenerate the disc. Data presented here on the innate human annulus progenitor cells: (i) assessed osteogenic, chondrogenic and adipogenic potentials of cultured human annulus cells; and (ii) defined progenitor-cell related gene expression patterns. Verification of the presence of progenitor cells within primary human disc tissue also used immunohistochemical identification of cell surface markers and microarray analyses. Differentiation analysis in cell cultures demonstrated a viable progenitor cell pool within Thompson grades III-IV discs. Osteogenesis was present in 8 out of 11 cultures (73%), chondrogenesis in 8 of 11 (73%), and adipogenesis in 6 of 6 (100%). Immunolocalization was positive for CD29, CD44, CD105, and CD14 (mean values 80.2%, 81.5%, 85.1%, and 88.6%, respectively); localization of CD45 and CD34 was negative in disc tissue. Compared to controls, surgical discs showed significantly downregulated genes with recognized progenitor cell functions: TCF7L2 (2.7 fold), BMI1 (3.8 fold), FGF receptor 2 (2 fold), PAFAH1B1 (2.3 fold), and GSTP1 (9 fold). Compared to healthier grade I/II discs, grade III/IV discs showed significantly upregulated XRCC5 (3.6 fold), TCF7L2 (6 fold), GSTP1 (3.7 fold), and BMI1 (3 fold). Additional significant cell marker analyses showed expression of platelet-derived growth factor receptor alpha, CD90, CD73, and STRO-1. Statement of Clinical Significance: Findings provide the first identification of progenitor cells in annulus specimens from older, more degenerate discs (in contrast to earlier studies of healthier discs or nondegenerative specimens from teenagers). Findings also increase knowledge on progenitor cells present in the disc and suggest their value in potential future utilization for regeneration and disc cell therapy. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1351-1360, 2016. PMID- 27249628 TI - Total Synthesis of Millingtonine. AB - Millingtonine is a glycosidic alkaloid that exists as a pair of pseudo enantiomeric diastereomers. Consideration of the likely biosynthetic origins of this unusual natural product has resulted in the development of a seven-step total synthesis. Results from this synthetic work provide evidence in support of a proposed network of biosynthetic pathways that can account for the formation of several phenylethanoid natural products. PMID- 27249629 TI - Assessment of semiempirical enthalpy of formation in solution as an effective energy function to discriminate native-like structures in protein decoy sets. AB - In this work, we tested the PM6, PM6-DH+, PM6-D3, and PM7 enthalpies of formation in aqueous solution as scoring functions across 33 decoy sets to discriminate native structures or good models in a decoy set. In each set these semiempirical quantum chemistry methods were compared according to enthalpic and geometric criteria. Enthalpically, we compared the methods according to how much lower was the enthalpy of each native, when compared with the mean enthalpy of its set. Geometrically, we compared the methods according to the fraction of native contacts (Q), which is a measure of geometric closeness between an arbitrary structure and the native. For each set and method, the Q of the best decoy was compared with the Q0 , which is the Q of the decoy closest to the native in the set. It was shown that the PM7 method is able to assign larger energy differences between the native structure and the decoys in a set, arguably because of a better description of dispersion interactions, however PM6-DH+ was slightly better than the rest at selecting geometrically good models in the absence of a native structure in the set. (c) 2016 Wiley Periodicals, Inc. PMID- 27249638 TI - Girls can play ball: Stereotype threat reduces variability in a motor skill. AB - The majority of research on stereotype threat shows what is expected: threat debilitates performance. However, facilitation is also possible, although seldom reported. This study investigated how stereotype threat influences novice females when performing the sensorimotor task of bouncing a ball to a target. We tested the predictions of two prevailing accounts for debilitation and facilitation due to sterotype threat effects: working memory and mere effort. Experimental results showed that variability in performance decreased more in stigmatized females than in control females, consistent with the prediction of the mere effort account, but inconsistent with the working memory account. These findings suggest that stereotype threat effects may be predicated upon the correctness of the dominant motor behavior, rather than on a novice-expert distinction or task difficulty. Further, a comprehensive understanding should incorporate the fact that stereotype threat can facilitate, as well as debilitate, performance. PMID- 27249639 TI - From the Bob/Kirk effect to the Benoit/Eric effect: Testing the mechanism of name sound symbolism in two languages. AB - Although it is often assumed that language involves an arbitrary relationship between form and meaning, many studies have demonstrated that nonwords like maluma are associated with round shapes, while nonwords like takete are associated with sharp shapes (i.e., the Maluma/Takete effect, Kohler, 1929/1947). The majority of the research on sound symbolism has used nonwords, but Sidhu and Pexman (2015) recently extended this effect to existing labels: real English first names (i.e., the Bob/Kirk effect). In the present research we tested whether the effects of name sound symbolism generalize to French speakers (Experiment 1) and French names (Experiment 2). In addition, we assessed the underlying mechanism of name sound symbolism, investigating the roles of phonology and orthography in the effect. Results showed that name sound symbolism does generalize to French speakers and French names. Further, this robust effect remained the same when names were presented in a curved vs. angular font (Experiment 3), or when the salience of orthographic information was reduced through auditory presentation (Experiment 4). Together these results suggest that the Bob/Kirk effect is pervasive, and that it is based on fundamental features of name phonemes. PMID- 27249640 TI - Assessment of diabetes care and the healthcare system in economically and transport underdeveloped rural mountain areas of western China: A cross-sectional survey. AB - BACKGROUND: The aim of the present study was to assess the quality of diabetes care and characteristics of the healthcare system in underdeveloped rural mountain areas of western China. METHODS: Questionnaires were used to collect data from 288 diabetic patients with a multistage cluster sampling method in Zhongjiang County (Sichuan Province) between October 2009 and April 2010. Sixty two village clinics, 23 town health centers, and a county central hospital were included to assess the availability of diabetes-related medical resources, in addition to diabetes-related medical insurance, reimbursement policies, and manpower. RESULTS: Of 288 patients, 38.2 % monitored their blood glucose regularly. Targets for fasting blood glucose (<=7 mmol/L) and blood pressure (<=130/80 mmHg) were achieved by 7.6 % and 9.7 % of patients, respectively. On average, each patient paid US$120 out of pocket annually for out-patient diabetes care, with a maximum US$86 reimbursed. The county central hospital was the only healthcare facility in the county that could provide all essential diabetes related drugs and process-of-care measures and tests, except measures of HbA1c and the urinary albumin: creatinine ratio. Insulin was not available at village clinics, and only 29 % of village clinics had glucometers. "Certified" doctors were not available to provide primary care in village clinics. CONCLUSIONS: The quality of diabetes care was quite poor in underdeveloped rural mountain areas of western China. Recommendations for further intervention research to improve diabetes healthcare include increasing investment in medical infrastructure, improving the availability of essential drugs and process measures, organizing regular diabetes patient education, and recruiting village doctors. PMID- 27249641 TI - Ex vivo mammalian prions are formed of paired double helical prion protein fibrils. AB - Mammalian prions are hypothesized to be fibrillar or amyloid forms of prion protein (PrP), but structures observed to date have not been definitively correlated with infectivity and the three-dimensional structure of infectious prions has remained obscure. Recently, we developed novel methods to obtain exceptionally pure preparations of prions from mouse brain and showed that pathogenic PrP in these high-titre preparations is assembled into rod-like assemblies. Here, we have used precise cell culture-based prion infectivity assays to define the physical relationship between the PrP rods and prion infectivity and have used electron tomography to define their architecture. We show that infectious PrP rods isolated from multiple prion strains have a common hierarchical assembly comprising twisted pairs of short fibres with repeating substructure. The architecture of the PrP rods provides a new structural basis for understanding prion infectivity and can explain the inability to systematically generate high-titre synthetic prions from recombinant PrP. PMID- 27249643 TI - Correction: Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005244.]. PMID- 27249644 TI - Orthogonal Discrimination among Functional Groups in Ullmann-Type C-O and C-N Couplings. AB - The copper-catalyzed arylation of nucleophiles has been established as an efficient methodology for the formation of C-C and C-heteroatom bonds. Considering the advances during the last two decades, the ligand choice plays a key role in such transformations and can strongly influence the catalytic efficiency. The applicability of these Ullmann-type coupling reactions regarding the orthogonal selectivity of different functional groups constitutes a challenging subject for current synthetic strategies. Herein, we report a useful toolkit of Cu-based catalysts for the chemoselective arylation of a wide-range of nucleophiles in competitive reactions using aryl iodides and bromides. We show in this work that the arylation of all kinds of amides can be orthogonal to that of amines (aliphatic or aromatic) and phenol derivatives. This high chemoselectivity can be governed by the use of different ligands, yielding the desired coupling products under mild conditions. The selectivity trends are maintained for electronically biased iodobenzene and bromobenzene electrophiles. Radical clock experiments discard the occurrence of radical-based mechanisms. PMID- 27249642 TI - Structure of astrotactin-2: a conserved vertebrate-specific and perforin-like membrane protein involved in neuronal development. AB - The vertebrate-specific proteins astrotactin-1 and 2 (ASTN-1 and ASTN-2) are integral membrane perforin-like proteins known to play critical roles in neurodevelopment, while ASTN-2 has been linked to the planar cell polarity pathway in hair cells. Genetic variations associated with them are linked to a variety of neurodevelopmental disorders and other neurological pathologies, including an advanced onset of Alzheimer's disease. Here we present the structure of the majority endosomal region of ASTN-2, showing it to consist of a unique combination of polypeptide folds: a perforin-like domain, a minimal epidermal growth factor-like module, a unique form of fibronectin type III domain and an annexin-like domain. The perforin-like domain differs from that of other members of the membrane attack complex-perforin (MACPF) protein family in ways that suggest ASTN-2 does not form pores. Structural and biophysical data show that ASTN-2 (but not ASTN-1) binds inositol triphosphates, suggesting a mechanism for membrane recognition or secondary messenger regulation of its activity. The annexin-like domain is closest in fold to repeat three of human annexin V and similarly binds calcium, and yet shares no sequence homology with it. Overall, our structure provides the first atomic-resolution description of a MACPF protein involved in development, while highlighting distinctive features of ASTN-2 responsible for its activity. PMID- 27249645 TI - Basics to perform and present statistical analyses in scientific biomedical reports. Part 2. PMID- 27249647 TI - Validation of NINDS-VCI Neuropsychology Protocols for Vascular Cognitive Impairment in Taiwan. AB - OBJECTIVE: To validate the three time-difference neuropsychological protocols developed by the National Institute of Health/National Institute of Neurological Disorders and Stroke (NINDS) and the Canadian Stroke Network for assessment of vascular cognitive impairment (VCI) in Mandarin-speaking subjects and to investigate the clinical application of the shortest form. METHODS: Patients aged 50 years or older who had a stroke were invited to participate in the study. Clinical diagnosis of VCI was made. The NINDS-VCI Neuropsychology Protocols, 60-, 30-, and two 5-minute protocols, were administered. The criteria validities of the cognitive protocols against the diagnoses of stroke and VCI were determined via Receiver Operating Characteristic (ROC) analysis. The optimal cut-off point for the 5-minute protocols total score was estimated for clinical use in screening. RESULTS: Eighty-three patients and 53 controls were recruited during the study period. Patients with stroke performed more poorly than the control group in the three neuropsychological protocols. Forty-two patients with stroke were diagnosed with VCI. VCI was used as the standard to estimate the criteria validities. The area under the ROC curve was 0.78, 0.80, 0.75, and 0.73 for the 60-, 30-, 5-mintue protocol-A and 5-minute protocol-B, respectively. CONCLUSION: These modified neuropsychological protocols can be used as valid instruments when performing comprehensive cognitive assessment or for screening of VCI in Taiwan. PMID- 27249646 TI - APOBEC4 Enhances the Replication of HIV-1. AB - APOBEC4 (A4) is a member of the AID/APOBEC family of cytidine deaminases. In this study we found a high mRNA expression of A4 in human testis. In contrast, there were only low levels of A4 mRNA detectable in 293T, HeLa, Jurkat or A3.01 cells. Ectopic expression of A4 in HeLa cells resulted in mostly cytoplasmic localization of the protein. To test whether A4 has antiviral activity similar to that of proteins of the APOBEC3 (A3) subfamily, A4 was co-expressed in 293T cells with wild type HIV-1 and HIV-1 luciferase reporter viruses. We found that A4 did not inhibit the replication of HIV-1 but instead enhanced the production of HIV-1 in a dose-dependent manner and seemed to act on the viral LTR. A4 did not show detectable cytidine deamination activity in vitro and weakly interacted with single-stranded DNA. The presence of A4 in virus producer cells enhanced HIV-1 replication by transiently transfected A4 or stably expressed A4 in HIV susceptible cells. APOBEC4 was capable of similarly enhancing transcription from a broad spectrum of promoters, regardless of whether they were viral or mammalian. We hypothesize that A4 may have a natural role in modulating host promoters or endogenous LTR promoters. PMID- 27249648 TI - Effects of a novel NADPH oxidase inhibitor (S42909) on wound healing in an experimental ischemic excisional skin model. AB - Chronic wounds are a serious healthcare problem. As non-healing wounds involve continuous pathologic inflammatory stage, research is focused on anti inflammatory treatments. Our objective was to analyze the effect of S42909, a potent NADPH oxidase inhibitor activity, with vascular anti-inflammatory properties. An ischemic rabbit ear ulcer model (24 New Zealand white rabbits) was used to evaluate the reepithelialization/contraction areas, anti-/pro inflammatory cytokines mRNA (TGF-beta1/IL-10/IFN-gamma/VEGF) by qRT-PCR, collagen I/III deposition, and neovascularization (TGF-beta1/VEGF) by morphological and immunohistochemical analyses. Three different doses were administered by gavage for 2 weeks: 10 and 30 mg/kg/d in self-microemulsion drug delivery system (SMEDDS) and 100 mg/kg/d in arabic gum. Each vehicle was used as control. No signs of infection or necrosis were found. Reepithelialization was almost complete whatever the groups reaching 95% at the dose of 100 mg/kg. Wound contraction was significantly reduced in all S42909-treated groups. A significant increase in anti-inflammatory cytokines TGF-beta1 mRNA and IL-10 mRNA was observed at the dose of 100 and 30 mg/kg/d, respectively. No changes were observed in pro-inflammatory factors INF-gamma and VEGF mRNA. Ischemic skin wound areas had scarce expression of collagen I/III and showed rich glycosaminoglycans content. Treatment increased the collagen deposition and TGF-beta1 protein expression and decreased glycosaminoglycan content dose dependently; however, no effect in VEGF was appreciated. Therefore, our results indicate that S42909 improved healing process by dampening excessive inflammation and facilitating collagen deposition without wound contraction phenomena. S42909 might be a promising therapy to treat chronic wounds as venous leg ulcers. PMID- 27249649 TI - Impact of Insertion Sequences and Recombination on the Population Structure of Staphylococcus haemolyticus. AB - Staphylococcus haemolyticus is one of the most common pathogens associated with medical-device related infections, but its molecular epidemiology is poorly explored. In the current study, we aimed to better understand the genetic mechanisms contributing to S. haemolyticus diversity in the hospital environment and their impact on the population structure and clinical relevant phenotypic traits. The analysis of a representative S. haemolyticus collection by multilocus sequence typing (MLST) has identified a single highly prevalent and diverse genetic lineage of nosocomial S. haemolyticus clonal complex (CC) 29 accounting for 91% of the collection of isolates disseminated worldwide. The examination of the sequence changes at MLST loci during clonal diversification showed that recombination had a higher impact than mutation in shaping the S. haemolyticus population. Also, we ascertained that another mechanism contributing significantly to clonal diversification and adaptation was mediated by insertion sequence (IS) elements. We found that all nosocomial S. haemolyticus, belonging to different STs, were rich in IS1272 copies, as determined by Southern hybridization of macrorestriction patterns. In particular, we observed that the chromosome of a S. haemolyticus strain within CC29 was highly unstable during serial growth in vitro which paralleled with IS1272 transposition events and changes in clinically relevant phenotypic traits namely, mannitol fermentation, susceptibility to beta-lactams, biofilm formation and hemolysis. Our results suggest that recombination and IS transposition might be a strategy of adaptation, evolution and pathogenicity of the major S. haemolyticus prevalent lineage in the hospital environment. PMID- 27249650 TI - High Levels of Sample-to-Sample Variation Confound Data Analysis for Non-Invasive Prenatal Screening of Fetal Microdeletions. AB - Our goal was to test the hypothesis that inter-individual genomic copy number variation in control samples is a confounding factor in the non-invasive prenatal detection of fetal microdeletions via the sequence-based analysis of maternal plasma DNA. The database of genomic variants (DGV) was used to determine the "Genomic Variants Frequency" (GVF) for each 50kb region in the human genome. Whole genome sequencing of fifteen karyotypically normal maternal plasma and six CVS DNA controls samples was performed. The coefficient of variation of relative read counts (cv.RTC) for these samples was determined for each 50kb region. Maternal plasma from two pregnancies affected with a chromosome 5p microdeletion was also sequenced, and analyzed using the GCREM algorithm. We found strong correlation between high variance in read counts and GVF amongst controls. Consequently we were unable to confirm the presence of the microdeletion via sequencing of maternal plasma samples obtained from two sequential affected pregnancies. Caution should be exercised when performing NIPT for microdeletions. It is vital to develop our understanding of the factors that impact the sensitivity and specificity of these approaches. In particular, benign copy number variation amongst controls is a major confounder, and their effects should be corrected bioinformatically. PMID- 27249652 TI - Friction and nonlinear dynamics. AB - The nonlinear dynamics associated with sliding friction forms a broad interdisciplinary research field that involves complex dynamical processes and patterns covering a broad range of time and length scales. Progress in experimental techniques and computational resources has stimulated the development of more refined and accurate mathematical and numerical models, capable of capturing many of the essentially nonlinear phenomena involved in friction. PMID- 27249651 TI - HIF-1alpha and HIF-2alpha induced angiogenesis in gastrointestinal vascular malformation and reversed by thalidomide. AB - Thalidomide is used in clinical practice to treat gastrointestinal vascular malformation (GIVM), but the pathogenesis of GIVM is not clear. Hypoxia inducible factor 1 alpha (HIF-1alpha) and 2 alpha (HIF-2alpha/EPAS1) are in the same family and act as master regulators of the adaptive response to hypoxia. HIF-1alpha and HIF-2alpha are up-regulated in vascular malformations in intestinal tissues from GIVM patients, but not in adjacent normal vessels. Therefore, we investigated the role of HIF-1alpha and HIF-2alpha during angiogenesis and the mechanism of thalidomide action. In vitro experiments confirmed that vascular endothelial growth factor (VEGF) was a direct target of HIF-2alpha and that HIF-1alpha and HIF-2alpha regulated NOTCH1, Ang2, and DLL4, which enhanced vessel-forming of endothelial cells. Thalidomide down-regulated the expression of HIF-1alpha and HIF-2alpha and inhibited angiogenesis. In vivo zebrafish experiments suggested that HIF-2alpha overexpression was associated with abnormal subintestinal vascular (SIV) sprouting, which was reversed by thalidomide. This result indicated that thalidomide regulated angiogenesis via the inhibition of HIF 1alpha and HIF-2alpha expression, which further regulated downstream factors, including VEGF, NOTCH1, DLL4, and Ang2. The abnormally high expression of HIF 1alpha and HIF-2alpha may contribute to GIVM. PMID- 27249653 TI - Establishment of a Wheat Cell-Free Synthesized Protein Array Containing 250 Human and Mouse E3 Ubiquitin Ligases to Identify Novel Interaction between E3 Ligases and Substrate Proteins. AB - Ubiquitination is a key post-translational modification in the regulation of numerous biological processes in eukaryotes. The primary roles of ubiquitination are thought to be the triggering of protein degradation and the regulation of signal transduction. During protein ubiquitination, substrate specificity is mainly determined by E3 ubiquitin ligase (E3). Although more than 600 genes in the human genome encode E3, the E3s of many target proteins remain unidentified owing to E3 diversity and the instability of ubiquitinated proteins in cell. We demonstrate herein a novel biochemical analysis for the identification of E3s targeting specific proteins. Using wheat cell-free protein synthesis system, a protein array containing 227 human and 23 mouse recombinant E3s was synthesized. To establish the high-throughput binding assay using AlphaScreen technology, we selected MDM2 and p53 as the model combination of E3 and its target protein. The AlphaScreen assay specifically detected the binding of p53 and MDM2 in a crude translation mixture. Then, a comprehensive binding assay using the E3 protein array was performed. Eleven of the E3s showed high binding activity, including four previously reported E3s (e.g., MDM2, MDM4, and WWP1) targeting p53. This result demonstrated the reliability of the assay. Another interactors, RNF6 and DZIP3-which there have been no report to bind p53-were found to ubiquitinate p53 in vitro. Further analysis showed that RNF6 decreased the amount of p53 in H1299 cells in E3 activity-dependent manner. These results suggest the possibility that the RNF6 ubiquitinates and degrades p53 in cells. The novel in vitro screening system established herein is a powerful tool for finding novel E3s of a target protein. PMID- 27249655 TI - Effect of Foot Progression Angle and Lateral Wedge Insole on a Reduction in Knee Adduction Moment. AB - This study evaluated the effect of foot progression angle on the reduction in knee adduction moment caused by a lateral wedged insole during walking. Twenty healthy, young volunteers walked 10 m at their comfortable velocity wearing a lateral wedged insole or control flat insole in 3 foot progression angle conditions: natural, toe-out, and toe-in. A 3-dimensional rigid link model was used to calculate the external knee adduction moment, the moment arm of ground reaction force to knee joint center, and the reduction ratio of knee adduction moment and moment arm. The result indicated that the toe-out condition and lateral wedged insole decreased the knee adduction moment in the whole stance phase. The reduction ratio of the knee adduction moment and the moment arm exhibited a close relationship. Lateral wedged insoles decreased the knee adduction moment in various foot progression angle conditions due to decrease of the moment arm of the ground reaction force. Moreover, the knee adduction moment during the toe-out gait with lateral wedged insole was the smallest due to the synergistic effect of the lateral wedged insole and foot progression angle. Lateral wedged insoles may be a valid intervention for patients with knee osteoarthritis regardless of the foot progression angle. PMID- 27249654 TI - Effects of Sublethal Concentrations of Cyantraniliprole on the Development, Fecundity and Nutritional Physiology of the Black Cutworm Agrotis ipsilon (Lepidoptera: Noctuidae). AB - To better understand the sublethal effects of cyantraniliprole on the black cutworm Agrotis ipsilon (Lepidoptera: Noctuidae), several studies were carried out to investigate sublethal effects on development stages, population parameters, feeding indices and nutrient content of A. ipsilon. The result of a bioassay showed that cyantraniliprole had high toxicity against A. ipsilon fourth instar larvae with an LC50 of 0.354 MUg.g-1 using an artificial diet. Compared with controls, sublethal doses of cyantraniliprole at LC5, LC20 and LC40 levels prolonged larval and pupal duration and extended mean generation time and total preovipositional period. In addition, survival rate, reproductive value, intrinsic and finite rates of increase and net reproduction rate declined significantly. Meanwhile, cyantraniliprole had markedly antifeedant effects; decreased the relative growth rate (RGR), the relative consumption rate (RCR), the efficiency of conversion of ingested food (ECI), the efficiency of conversion of digested food (ECD); and increased the approximate digestibility (AD) significantly. This phenomenon contributed to the decrease of nutrient contents, including lipids, protein and carbohydrates, to the point that insufficient energy was available for normal growth. Therefore, sublethal concentrations of cyantraniliprole decreased growth speed and reduced population reproduction of A. ipsilon. This result provides information useful in integrated pest management (IPM) programs for A. ipsilon. PMID- 27249657 TI - Community-based Participatory Research Is Needed to Address Pulmonary Health Disparities. AB - Socioeconomic and racial disparities in the outcomes of medical management remain common across pulmonary diseases in the United States and worldwide. Acknowledging this, the American Thoracic Society recently put forth recommendations to advance respiratory health equity. Through engagement of vulnerable communities in search of collaborative solutions to improve health disparities, community-based participatory research embodies concepts essential to the American Thoracic Society mission for respiratory health equity. The purpose of this commentary is to provide an overview of the principles of community-based participatory research and the application of this approach to addressing inequity in the outcomes of treatment for lung disease. Community based participatory research aims to decrease health disparities by recognizing the social and ecological paradigms of health care and by partnering community members with academic researchers in all aspects of the research process. Community partners are uniquely poised to offer insight into local culture, circumstances that guide health behaviors, and other challenges to improve their own community's health. Sustainable interventions, either through strengthening existing community assets or through community empowerment and local capacity building throughout the research process, are essential to the success of community-based participatory research. The National Institutes of Health and other funding agencies offer funding opportunities to support specific interventions aimed at engaging community members in the research process. In pulmonary medicine, community-based initiatives have focused primarily on improving pediatric asthma outcomes. Using a community-based approach in adult asthma and other pulmonary diseases could be an ideal manner in which to decrease pulmonary health disparities. PMID- 27249656 TI - Statistical modeling of ICEEG features that determine resection planning. AB - OBJECT: The interpretation of intracranial EEG (ICEEG) recordings is a complex balance of the significance of specific rhythms and their relative timing to seizure onset. Ictal and interictal findings are evaluated in light of findings from cortical stimulation of eloquent cortex to determine the area of resection. PATIENTS AND METHODS: Patients with ICEEG electrodes and subsequent surgical resection were retrospectively identified. Only the first 15s of ictal activity, which was divided into five 3-s epochs, was considered. Every electrode in each patient was considered a separate observation in a logistic regression model to predict whether the cortex under a given electrode was included in the planned resection. RESULTS: 19 included patients had a total of 37 unique seizures. Recordings from a total of 1306 electrodes were analyzed. The strongest predictors of resection of cortex underlying a given electrode was the presence of low-voltage fast activity in Epoch 1, rhythmic spikes in Epoch 1, interictal paroxysmal fast activity, and low-voltage fast activity in Epoch 2. High amplitude beta spikes and rhythmic slow waves were also significant predictors in Epoch 1. Interictal spikes had a higher odds ratio of affecting the planned resection if described as "continuous" or "very frequent". The presence of motor or language cortex were the strongest negative predictors of resecting underlying cortex. CONCLUSIONS: Here we describe a novel model of ictal and interictal patterns significantly associated with the inclusion of cortex underlying a given ICEEG electrode in the surgical resection plan. PMID- 27249658 TI - Risk Factors for Antimicrobial Resistance in Escherichia coli in Pigs Receiving Oral Antimicrobial Treatment: A Systematic Review. AB - The aim of this literature review was to identify risk factors in addition to antimicrobial treatment for antimicrobial resistance (AMR) occurrence in commensal Escherichia coli in pigs. A variety of studies were searched in 2014 and 2015. Studies identified as potentially relevant were assessed against eligibility criteria such as observation or experiment (no review), presentation of risk factors in addition to (single dosage) antimicrobial use, risk factors for but not resulting from AMR, and the same antimicrobial used and tested. Thirteen articles (nine on observational, four on experimental studies) were finally selected as relevant. It was reported that space allowance, production size/stage, cleanliness, entry of animals and humans into herds, dosage/frequency/route of administration, time span between treatment and sampling date, herd size, distance to another farm, coldness, and season had an impact on AMR occurrence. Associations were shown by one to four studies per factor and differed in magnitude, direction, and level of significance. The risk of bias was unclear in nearly half of the information of observational studies and in most of the information from experimental studies. Further research on the effects of specific management practices is needed to develop well-founded management advice. PMID- 27249659 TI - What Torture Survivors Teach Assessors About Being More Fully Human. AB - This article illustrates the complex sociocultural components in the forensic psychological assessment of a young Ethiopian woman's claim for political asylum due to a well-founded fear of persecution and for relief under the Convention Against Torture. It draws attention to the subtle social and cultural influences in the practice of forensic psychological assessment with an emphasis of reflective practice, which is contextualized in the interpersonal theory of Sullivan. In the interpersonal approach, the essential work of the assessor is to pay careful attention to the microinteractions between the client and the assessor as reflections of the interpersonal (meaning social and cultural) processes, eschewing the illusion of objectivity. In this case study, I illustrate the particular cultural dilemmas for client and assessor in conducting a forensic assessment of psychological trauma, including cross-cultural, gender, and legal difficulties in arriving at an informed, objective, and compassionate assessment of an individual seeking asylum after an especially brutal experience of torture. I argue that collaborative therapeutic assessment methods adapted for forensic practice offer an approach to assessment of psychological trauma that provides more accurate and compassionate assessment than so-called neutral standard forensic assessment practice. PMID- 27249660 TI - Clinical and genetic predictors of dipeptidyl peptidase-4 inhibitor treatment response in Type 2 diabetes mellitus. AB - AIM: To determine the clinical and genetic predictors of the dipeptidyl peptidase 4 (DPP-4) inhibitor treatment response in Type 2 diabetes mellitus (T2DM) patients. PATIENTS & METHODS: DPP4, WFS1 and KCNJ11 gene polymorphisms were genotyped in a cohort study of 662 T2DM patients treated with DPP-4 inhibitors sitagliptin, vildagliptin or linagliptin. Genotyping was performed by Applied Biosystems TaqMan SNP genotyping assay. RESULTS: Patients with triglyceride levels less than 1.7 mmol/l (odds ratio [OR]: 2.2.; 95% CI: 1.031-4.723), diastolic blood pressure (DBP) less than 90 mmHg (OR: 1.7; 95% CI: 1.009-2.892) and KCNJ11 rs2285676 (genotype CC) (OR: 2.0; 95% CI: 1.025-3.767) were more likely to response to DPP-4 inhibitor treatment compared with other patients, as measured by HbA1c levels. CONCLUSION: Triglycerides, DBP and KCNJ11 rs2285676 are predictors of the DPP-4 inhibitor treatment response in T2DM patients. PMID- 27249662 TI - Observation of Organic Molecules at the Aerosol Surface. AB - Organic molecules at the gas-particle interface of atmospheric aerosols influence the heterogeneous chemistry of the aerosol and impact climate properties. The ability to probe the molecules at the aerosol particle surface in situ therefore is important but has been proven challenging. We report the first successful observations of molecules at the surface of laboratory-generated aerosols suspended in air using the surface-sensitive technique second harmonic light scattering (SHS). As a demonstration, we detect trans-4-[4-(dibutylamino)styryl] 1-methylpyridinium iodide and determine its population and adsorption free energy at the surface of submicron aerosol particles. This work illustrates a new and versatile experimental approach for studying how aerosol composition may affect the atmospheric properties. PMID- 27249661 TI - A rare case of rapidly progressive dementia with elevated RT-QuIC and negative 14 3-3 and tau proteins. AB - Creutzfeldt-Jakob disease (CJD) is characterized by rapidly progressing dementia with death usually occurring within 6 months. There is no verified disease specific pre-mortem diagnostic test besides brain biopsy. We describe a 66 y old previously high functioning male who presented with a 5 month history of rapidly progressive dementia. Neurological examination revealed a score of 19/30 on MOCA testing. An extensive workup into various causes of dementia including electroencephalography and imaging studies was unremarkable. The cerebrospinal fluid was sent to National Prion Disease Center and it revealed elevated RT-QuIC levels with negative 14-3-3 and T tau proteins. Based on literature review, our case is one of few living subjects with elevated RT-QuIC levels and negative 14-3 3 and tau proteins. PMID- 27249663 TI - Multidisciplinary discussion for diagnosis of interstitial lung disease in real life. PMID- 27249664 TI - Phytovolatilization of Organic Contaminants. AB - Plants can interact with a variety of organic compounds, and thereby affect the fate and transport of many environmental contaminants. Volatile organic compounds may be volatilized from stems or leaves (direct phytovolatilization) or from soil due to plant root activities (indirect phytovolatilization). Fluxes of contaminants volatilizing from plants are important across scales ranging from local contaminant spills to global fluxes of methane emanating from ecosystems biochemically reducing organic carbon. In this article past studies are reviewed to clearly differentiate between direct- and indirect-phytovolatilization and we discuss the plant physiology driving phytovolatilization in different ecosystems. Current measurement techniques are also described, including common difficulties in experimental design. We also discuss reports of phytovolatilization in the literature, finding that compounds with low octanol-air partitioning coefficients are more likely to be phytovolatilized (log KOA < 5). Reports of direct phytovolatilization at field sites compare favorably to model predictions. Finally, future research needs are presented that could better quantify phytovolatilization fluxes at field scale. PMID- 27249665 TI - Gadolinium(III) Porpholactones as Efficient and Robust Singlet Oxygen Photosensitizers. AB - Construction of Gd(III) photosensitizers is important for designing theranostic agents owing to the unique properties arising from seven unpaired f electrons of the Gd(3+) ion. Combining these with the advantages of porpholactones with tunable NIR absorption, we herein report the synthesis of Gd(III) complexes Gd-1 4 (1, porphyrin; 2, porpholactone; 3 and 4, cis- and trans-porphodilactone, respectively) and investigated their function as singlet oxygen ((1) O2 ) photosensitizers. These Gd complexes displayed (1) O2 quantum yields (PhiDelta s) from 0.64-0.99 with the order Gd-1(3) Sigmag transition of (1) O2 . In particular, Gd-4 is capable of excitation in the visible to NIR region (400-700 nm) with a quantum yield near unity. These Gd complexes were first demonstrated as efficient photosensitizers in photocatalysis such as oxidative C H bond functionalization of secondary or tertiary amines, and the oxygenation of the natural product cholesterol. Finally, after glycosylation, these water soluble Gd complexes showed potential applications in photodynamic therapy (PDT) in HeLa cells. This work revealed that Gd(III) complexes of "bioinspired" beta modified porpholactones are efficient NIR photosensitizers and form a chemical basis to construct appealing photocatalysts and theranostic agents based on lanthanides. PMID- 27249666 TI - In Vivo Goblet Cell Density as a Potential Indicator of Glaucoma Filtration Surgery Outcome. AB - PURPOSE: We analyzed the preoperative conjunctival goblet cell density (GCD), MUC5AC, and HLA-DR in glaucomatous patients undergoing trabeculectomy, using laser scanning confocal microscopy (LSCM) and impression cytology (IC). METHODS: We enrolled 57 patients undergoing trabeculectomy. At baseline LSCM and IC were performed at the site planned for surgery; LSCM was repeated after 12 months at the bleb site. The main outcomes were: GCD, mean microcyst density (MMD) and area (MMA) at LSCM, MUC5AC, and HLA-DR positivity at IC, and IOP. The relationships between baseline GCD, and 12-month IOP, MMD, and MMA were analyzed. RESULTS: Trabeculectomy was successful in 39 patients (complete success in 27, Group 1; qualified in 12, Group 2), and unsuccessful in 18 (Group 3). At baseline IOP (mm Hg) was 27.2 +/- 3.12, 27.5 +/- 2.23, and 27.7 +/- 1.90 in Groups 1 to 3, respectively; GCD and MUC5AC positivity were higher in Group 1 compared to Groups 2 and 3 (P < 0.05); HLA-DR, MMD, and MMA were not significantly different among the groups. At 12 months, IOP reduced by 45.3%, 35.4%, and 12.8% in Groups 1 to 3, respectively. Goblet cell density did not change in Group 1, whereas it was reduced in Groups 2 and 3 (P < 0.05), with values lower in Group 3. Mean microcyst density and MMA increased in Groups 1 and 2 (P < 0.05), with values higher in Group 1 (P < 0.05). Baseline GCD positively correlated with 12-month IOP reduction (P < 0.001, r = 0.641), MMD (P < 0.05, r = 0.454), and MMA (P < 0.001, r = 0.541). CONCLUSIONS: Goblet cells positively affect the filtration ability after trabeculectomy; therefore, preoperative GCD could be considered as a potential in vivo biomarker of surgical success. PMID- 27249667 TI - Insight into the reaction mechanisms for oxidative addition of strong sigma bonds to an Al(i) center. AB - The oxidation addition of a series of sigma H-X bonds (X = H, B, C, Si, N, P, and O) to a single Al(i) supported by a (NacNac)(-) bidentate ligand ((NacNac)(-) = [ArNC(Me)CHC(Me)NAr](-) and Ar = 2,6-(i)Pr2C6H3) has been explored through extensive DFT calculations. The presented results show that activation and addition of these sigma bonds follow various reaction mechanisms, in which hydride transfer, proton transfer, and Al-X bond coupling steps are involved. The predicted free energy barriers for these oxidative additions range from 8 to 32 kcal mol(-1), and all the reactions are remarkably favorable thermodynamically. However, sterically hindered ligands, for most reactants, make the formation of the initial reactant complex difficult and may reduce the efficiency of the reaction. Calculations reveal a strong dependence of the reaction mechanism and low-energy channel on the bonding features of X-H and the local structural environments. PMID- 27249669 TI - Investigation of Four Different Laponite Clays as Stabilizers in Pickering Emulsion Polymerization. AB - Clay-armored polymer particles were prepared by emulsion polymerization in the presence of Laponite platelets that adsorb at the surface of latex particles and act as stabilizers during the course of the polymerization. While Laponite RDS clay platelets are most often used, the choice of the type of clay still remains an open issue that is addressed in the present article. Four different grades of Laponite were investigated as stabilizers in the emulsion polymerization of styrene. First, the adsorption isotherms of the clays, on preformed polystyrene particles, were determined by ICP-AES analysis of the residual clay in the aqueous phase. Adsorption of clay depended on the type of clay at low concentrations corresponding to adsorption as a monolayer. Adsorption of clay particles as multilayers was observed for all the grades above a certain concentration under the considered ionic strength (mainly due to the initiator ionic species). The stabilization efficiency of these clays was investigated during the polymerization reaction (free of any other stabilizer). The clays did not have the same effect on stabilization, which was related to differences in their compositions and in their adsorption isotherms. The different grades led to different polymer particles sizes and therefore to different polymerization reaction rates. Laponite RDS and S482 gave similar results, ensuring the best stabilization efficiency and the fastest reaction rate; the number of particles increased as the clay concentration increased. Stabilization with Laponite XLS gave the same particles size and number as the latter two clays at low clay concentrations, but it reached an upper limit in the number of nucleated polymer particles at higher concentrations indicating a decrease of stabilization efficiency at high concentrations. Laponite JS did not ensure a sufficient stability of the polymer particles, as the polymerization results were comparable to a stabilizer-free polymerization system. PMID- 27249668 TI - aPKC regulates apical localization of Lgl to restrict elongation of microridges in developing zebrafish epidermis. AB - Epithelial cells exhibit apical membrane protrusions, which confer specific functions to epithelial tissues. Microridges are short actin protrusions that are laterally long and form a maze-like pattern in the apical domain. They are widely found on vertebrate squamous epithelia including epidermis and have functions in mucous retention, membrane storage and abrasion resistance. It is largely unknown how the formation of these laterally long actin projections is regulated. Here, we show that antagonistic interactions between aPKC and Lgl-regulators of apical and basolateral domain identity, respectively,-control the length of microridges in the zebrafish periderm, the outermost layer of the epidermis. aPKC regulates the levels of Lgl and the active form of non-muscle myosinII at the apical cortex to prevent actin polymerization-dependent precocious fusion and elongation of microridges. Our data unravels the functional significance of exclusion of Lgl from the apical domain in epithelial cells. PMID- 27249670 TI - Napping-Ultra Flash Profile as a Tool for Category Identification and Subsequent Model System Formulation of Caramel Corn Products. AB - In a novel approach to formulation, the flash descriptive profiling technique Napping-Ultra Flash Profile (Napping-UFP) was used to characterize a wide range of commercial caramel corn products. The objectives were to identify product categories, develop model systems based on product categories, and correlate analytical parameters with sensory terms generated through the Napping-UFP exercise. In one 2 h session, 12 panelists participated in 4 Napping-UFP exercises, describing and grouping, on a 43*56 cm paper sheet, 12 commercial caramel corn samples by degree of similarity, globally and in terms of aroma-by mouth, texture, and taste. The coordinates of each sample's placement on the paper sheet and descriptive terms generated by the panelists were used to conduct Multiple Factor Analysis (MFA) and hierarchical clustering of the samples. Strong trends in the clustering of samples across the 4 Napping-UFP exercises resulted in the determination of 3 overarching types of commercial caramel corn: "small scale dark" (typified by burnt, rich caramel corn), "large-scale light" (typified by light and buttery caramel corn), and "large-scale dark" (typified by sweet and molasses-like caramel corn). Representative samples that best exemplified the properties of each category were used as guides in the formulation of 3 model systems that represent the spread of commercial caramel corn products. Analytical testing of the commercial products, including aw measurement, moisture content determination, and thermal characterization via differential scanning calorimetry, were conducted and results related to sensory descriptors using Spearman's correlation. PMID- 27249672 TI - Radiation-Induced Helium Nanobubbles Enhance Ductility in Submicron-Sized Single Crystalline Copper. AB - The workability and ductility of metals usually degrade with exposure to irradiation, hence the phrase "radiation damage". Here, we found that helium (He) radiation can actually enhance the room-temperature deformability of submicron sized copper. In particular, Cu single crystals with diameter of 100-300 nm and containing numerous pressurized sub-10 nm He bubbles become stronger, more stable in plastic flow and ductile in tension, compared to fully dense samples of the same dimensions that tend to display plastic instability (strain bursts). The sub 10 nm He bubbles are seen to be dislocation sources as well as shearable obstacles, which promote dislocation storage and reduce dislocation mean free path, thus contributing to more homogeneous and stable plasticity. Failure happens abruptly only after significant bubble coalescence. The current findings can be explained in light of Weibull statistics of failure and the beneficial effects of bubbles on plasticity. These results shed light on plasticity and damage developments in metals and could open new avenues for making mechanically robust nano- and microstructures by ion beam processing and He bubble engineering. PMID- 27249673 TI - Rapid Environmental Change Drives Increased Land Use by an Arctic Marine Predator. AB - In the Arctic Ocean's southern Beaufort Sea (SB), the length of the sea ice melt season (i.e., period between the onset of sea ice break-up in summer and freeze up in fall) has increased substantially since the late 1990s. Historically, polar bears (Ursus maritimus) of the SB have mostly remained on the sea ice year-round (except for those that came ashore to den), but recent changes in the extent and phenology of sea ice habitat have coincided with evidence that use of terrestrial habitat is increasing. We characterized the spatial behavior of polar bears spending summer and fall on land along Alaska's north coast to better understand the nexus between rapid environmental change and increased use of terrestrial habitat. We found that the percentage of radiocollared adult females from the SB subpopulation coming ashore has tripled over 15 years. Moreover, we detected trends of earlier arrival on shore, increased length of stay, and later departure back to sea ice, all of which were related to declines in the availability of sea ice habitat over the continental shelf and changes to sea ice phenology. Since the late 1990s, the mean duration of the open-water season in the SB increased by 36 days, and the mean length of stay on shore increased by 31 days. While on shore, the distribution of polar bears was influenced by the availability of scavenge subsidies in the form of subsistence-harvested bowhead whale (Balaena mysticetus) remains aggregated at sites along the coast. The declining spatio temporal availability of sea ice habitat and increased availability of human provisioned resources are likely to result in increased use of land. Increased residency on land is cause for concern given that, while there, bears may be exposed to a greater array of risk factors including those associated with increased human activities. PMID- 27249674 TI - Current therapies and future possibilities for drug development against liver stage malaria. AB - Malaria remains a global public health threat, with half of the world's population at risk. Despite numerous efforts in the past decade to develop new antimalarial drugs to surmount increasing resistance to common therapies, challenges remain in the expansion of the current antimalarial arsenal for the elimination of this disease. The requirement of prophylactic and radical cure activities for the next generation of antimalarial drugs demands that new research models be developed to support the investigation of the elusive liver stage of the malaria parasite. In this Review, we revisit current antimalarial therapies and discuss recent advances for in vitro and in vivo malaria research models of the liver stage and their importance in probing parasite biology and the discovery of novel drug candidates. PMID- 27249675 TI - Non-coding RNAs in muscle differentiation and musculoskeletal disease. AB - RNA is likely to be the most rediscovered macromolecule in biology. Periodically, new non-canonical functions have been ascribed to RNA, such as the ability to act as a catalytic molecule or to work independently from its coding capacity. Recent annotations show that more than half of the transcriptome encodes for RNA molecules lacking coding activity. Here we illustrate how these transcripts affect skeletal muscle differentiation and related disorders. We discuss the most recent scientific discoveries that have led to the identification of the molecular circuitries that are controlled by RNA during the differentiation process and that, when deregulated, lead to pathogenic events. These findings will provide insights that can aid in the development of new therapeutic interventions for muscle diseases. PMID- 27249676 TI - Metabolic regulation of immune responses: therapeutic opportunities. AB - Immune cell metabolism is dynamically regulated in parallel with the substantial changes in cellular function that accompany immune cell activation. While these changes in metabolism are important for facilitating the increased energetic and biosynthetic demands of activated cells, immune cell metabolism also has direct roles in controlling the functions of immune cells and shaping the immune response. A theme is emerging wherein nutrients, metabolic enzymes, and metabolites can act as an extension of the established immune signal transduction pathways, thereby adding an extra layer of complexity to the regulation of immunity. This Review will outline the metabolic configurations adopted by different immune cell subsets, describe the emerging roles for metabolic enzymes and metabolites in the control of immune cell function, and discuss the therapeutic implications of this emerging immune regulatory axis. PMID- 27249677 TI - Contextual and Individual Factors Influencing Periodontal Treatment Needs by Elderly Brazilians: A Multilevel Analysis. AB - OBJECTIVE: To assess the relationship between periodontal treatment needs by elderly Brazilians and contextual as well as individual variables. METHODS: A cross-sectional study was carried out to assess the need for clinical periodontal treatment, based on National Oral Health Survey (SB Brasil 2010) data on the presence of dental calculus, shallow (3-5 mm) and deep (>= 6 mm) periodontal pockets, and gingival bleeding in elderly people (n = 7,619). The contextual variables included the Municipal Human Development Index (MHDI), income inequality (Gini Index) and coverage of the municipal population by the Family Health Strategy (FHS) program oral health teams.<0} The individual variables were sex, income, education level and self-reported skin color. Multilevel logistic regression models were used to calculate the odds ratio (OR) and 95% confidence intervals (CI95%) between periodontal treatment needs and the contextual as well as individual variables. RESULTS: Gingival bleeding was found in 20.7% of the elderly analyzed (n = 1,577), dental calculus in 34% (n = 2,590), shallow periodontal pockets in 15.6% (n = 1,189), and deep periodontal pockets in 4.2% (n = 320). Individual factors were correlated with all the outcomes assessed. Sex was a protective factor in regard to gingival bleeding (OR = 0.87; CI95% 0.76 1.00), dental calculus (OR = 0.86; CI95% 0.75-0.99), shallow periodontal pockets (OR = 0.69; CI95% 0.60-0.80) and deep periodontal pockets (OR = 0.58; CI95% 0.45 0.74). It was found that fewer women needed treatment. Elderly people who self reported having nonwhite skin had higher chances of needing periodontal treatment. Skin color was a risk factor for gingival bleeding (OR = 1.32; CI95% 1.14-1.53), dental calculus (OR = 1.32; CI95%1.14-1.54) and shallow periodontal pockets (OR = 1.27; CI95% 1.09-1.49). Education level was associated with the presence of dental calculus (OR = 0.77; CI95% 0.66-0.89), shallow periodontal pockets (OR = 0.86; CI95% 0.73-1.00) and deep periodontal pockets (OR = 0.74; CI95% 0.57-0.97), thus acting as a risk factor for undereducated elderly people. There was a correlation between population coverage by the Family Health Strategy (FHS) program oral health teams and the presence of gingival bleeding (OR = 0.67; CI95% 0.52-0.88), shallow periodontal pockets (OR = 0.76; CI95% 0.58-0.98) and deep periodontal pockets (OR = 0.62; CI95% 0.44-0.89), making these teams act as a protective factor. CONCLUSIONS: This study showed evidence of the sociocontextual as well as individual sociodemographic characteristics influencing periodontal treatment needed by elderly Brazilians, based on the clinical features of periodontal disease. The results suggest the existence of inequality related to periodontal treatment needs among elderly Brazilians, especially in regard to sex and ethnicity, in addition to a potentially positive impact from the expansion of the Family Health Strategy (FHS) program oral health teams. PMID- 27249679 TI - Collaborative Practice in an Era of Multidisciplinary Care. PMID- 27249680 TI - Value in Oncology: Balance Between Quality and Cost. PMID- 27249678 TI - Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice. AB - Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice. PMID- 27249681 TI - Women's Health Issues for BRCA Mutation Carriers. PMID- 27249682 TI - Collective Wisdom: Lobular Carcinoma of the Breast. PMID- 27249683 TI - Challenges in Treating Premenopausal Women with Endocrine-Sensitive Breast Cancer. AB - For the hundreds of thousands of premenopausal women who are diagnosed annually with endocrine-sensitive breast cancer, treatment strategies are complex. For many, chemotherapy may not be necessary, and endocrine therapy decision making is paramount. Options for adjuvant endocrine regimens include tamoxifen for 5 years, tamoxifen for 10 years, ovarian function suppression (OFS) plus tamoxifen for 5 years, and OFS plus an aromatase inhibitor for 5 years. There are modest differences in efficacy between these regimens, with a benefit from OFS most obvious among patients with higher-risk disease; therefore, choosing which should be used for a given patient requires consideration of expected toxicities and patient preferences. An aromatase inhibitor cannot be safely prescribed without OFS in this setting. Additional research is needed to determine whether genomic tests such as Prosigna and Endopredict can help with decision making about optimal duration of endocrine therapy for premenopausal patients. Endocrine therapy side effects can include hot flashes, sexual dysfunction, osteoporosis, and infertility, all of which may impair quality of life and can encourage nonadherence with treatment. Ovarian function suppression worsens menopausal side effects. Hot flashes tend to be worse with tamoxifen/OFS, whereas sexual dysfunction and osteoporosis tend to be worse with aromatase inhibitors/OFS. Pregnancy is safe after endocrine therapy, and some survivors can conceive naturally. Still, embryo or oocyte cryopreservation should be considered at the time of diagnosis for patients with endocrine-sensitive disease who desire future childbearing, particularly if they will undergo chemotherapy. PMID- 27249684 TI - The Evolution of Triple-Negative Breast Cancer: From Biology to Novel Therapeutics. AB - Triple-negative breast cancer (TNBC) is clinically defined as lacking expression of the estrogen receptor (ER), progesterone receptor (ER), and HER2. Historically, TNBC has been characterized by an aggressive natural history and worse disease-specific outcomes compared with other breast cancer subtypes. The advent of next-generation sequencing (NGS) has allowed for the dissection of TNBC into molecular subtypes (i.e., basal-like, claudin-low). Within TNBC, several subtypes have emerged as "immune-activated," consistently illustrating better disease outcome. In addition, NGS has revealed a host of molecular features characteristic of TNBC, including high rates of TP53 mutations, PI3K and MEK pathway activation, and genetic similarities to serous ovarian cancers, including inactivation of the BRCA pathway. Identified genetic vulnerabilities of TNBC have led to promising therapeutic approaches, including DNA-damaging agents (i.e., platinum salts and PARP inhibitors), as well as immunotherapy. Platinum salts are routinely incorporated into the treatment of metastatic TNBC; however, best outcomes are observed among those with deficiencies in the BRCA pathway. Although the incorporation of platinum in the neoadjuvant care of patients with TNBC yields higher pathologic complete response (pCR) rates, the impact on longer-term outcome is less clear. The presence of immune infiltrate in TNBC has shown both a predictive and prognostic role. Checkpoint inhibitors, including PD-1 and PD-L1 inhibitors, are under investigation in the setting of metastatic TNBC and have shown responses in initial clinical trials. Finally, matching emerging therapeutic strategies to optimal subtype of TNBC is of utmost importance as we design future research strategies to improve patient outcome. PMID- 27249685 TI - Refining Breast Cancer Risk Stratification: Additional Genes, Additional Information. AB - Recent advances in genomic technology have enabled far more rapid, less expensive sequencing of multiple genes than was possible only a few years ago. Advances in bioinformatics also facilitate the interpretation of large amounts of genomic data. New strategies for cancer genetic risk assessment include multiplex sequencing panels of 5 to more than 100 genes (in which rare mutations are often associated with at least two times the average risk of developing breast cancer) and panels of common single-nucleotide polymorphisms (SNPs), combinations of which are generally associated with more modest cancer risks (more than twofold). Although these new multiple-gene panel tests are used in oncology practice, questions remain about the clinical validity and the clinical utility of their results. To translate this increasingly complex genetic information for clinical use, cancer risk prediction tools are under development that consider the joint effects of all susceptibility genes, together with other established breast cancer risk factors. Risk-adapted screening and prevention protocols are underway, with ongoing refinement as genetic knowledge grows. Priority areas for future research include the clinical validity and clinical utility of emerging genetic tests; the accuracy of developing cancer risk prediction models; and the long-term outcomes of risk-adapted screening and prevention protocols, in terms of patients' experiences and survival. PMID- 27249686 TI - Access to Cancer Therapeutics in Low- and Middle-Income Countries. AB - Cancer is rapidly becoming a major health care problem, especially in developing countries, where 60% of the world's total new cases are diagnosed. The success of new antineoplastic medicines and modern radiation devices to cure a good proportion of patients with cancer and to alleviate the suffering of many more has been achieved at a dramatic cost. Therefore, it has become mandatory for health care authorities and pharmaceutical companies to cooperate to use and develop resources in an efficient manner to improve health care delivery to patients with cancer worldwide. Regulatory harmonization is an important key to overcome delays in the approval process, whether for antineoplastic and pain control medicines or for essential medical devices. More emphasis on the significant role of opiates in pain control among patients with cancer is needed to overcome the ingrained belief in their potential for addiction. The World Health Organization (WHO) serves an important role in guiding priorities for health care and efficiently allocating resources by providing essential medicine lists (EMLs) and device lists. However, the financial challenge for access to health care is multi-tiered and requires collaboration between key stakeholders including pharmaceutical industry, local national health authorities, WHO, and other nonprofit, patient-oriented organizations. PMID- 27249687 TI - Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). AB - Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials. PMID- 27249688 TI - Treatment of Adult Lower-Grade Glioma in the Era of Genomic Medicine. AB - By convention, gliomas are histopathologically classified into four grades by the World Health Organization (WHO) legacy criteria, in which increasing grade is associated with worse prognosis and grades also are subtyped by presumed cell of origin. This classification has prognostic value but is limited by wide variability of outcome within each grade, so the classification is rapidly undergoing dramatic re-evaluation in the context of a superior understanding of the biologic heterogeneity and molecular make-up of these tumors, such that we now recognize that some low-grade gliomas behave almost like malignant glioblastoma, whereas other anaplastic gliomas have outcomes comparable to favorable low-grade gliomas. This clinical spectrum is partly accounted for by the dispersion of several molecular genetic alterations inherent to clinical tumor behavior. These molecular biomarkers have become important not only as prognostic factors but also, more critically, as predictive markers to drive therapeutic decision making. Some of these, in the near future, will likely also serve as potential therapeutic targets. In this article, we summarize the key molecular features of clinical significance for WHO grades II and III gliomas and underscore how the therapeutic landscape is changing. PMID- 27249689 TI - Transforming Clinical Trial Eligibility Criteria to Reflect Practical Clinical Application. AB - Historically, oncology clinical trials have focused on comparing a new drug's efficacy to the standard of care. However, as our understanding of molecular pathways in oncology has evolved, so has our ability to predict how patients will respond to a particular drug, and thus comparison with a standard therapy has become less important. Biomarkers and corresponding diagnostic testing are becoming more and more important to drug development but also limit the type of patient who may benefit from the therapy. Newer clinical trial designs have been developed to assess clinically meaningful endpoints in biomarker-enriched populations, and the number of modern, molecularly driven clinical trials are steadily increasing. At the same time, barriers to clinical trial enrollment have also grown. Many barriers contribute to nonenrollment in clinical trials, including patient, physician, institution, protocol, and regulatory barriers. At the protocol level, eligibility criteria have become a large roadblock to clinical trial accrual. Over time, eligibility criteria have become more and more restrictive. To accrue an adequate number of patients to molecularly driven trials, we should consider eligibility criteria carefully and attempt to reduce restrictive criteria. Reducing restrictive eligibility criteria will allow more patients to be eligible for clinical trial participation, will likely increase the speed of drug approvals, and will result in clinical trial results that more accurately reflect treatment of the population in the clinical setting. PMID- 27249690 TI - Multimodal Rectal Cancer Treatment: In Some Cases, Less May Be More. AB - A series of clinical trials in the last several decades has resulted in the development of multimodality treatment of locally advanced rectal cancer that includes neoadjuvant (preoperative) chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemoradiotherapy. Owing to this regimen, patients with locally advanced rectal cancer have better survival rates than patients with colon cancer, but at the cost of substantial morbidity and reduced quality of life. The challenge is to identify treatment approaches that maintain or even improve oncologic outcomes while preserving quality of life. We have identified different tumor characteristics that are associated with recurrence and probability of survival for locally advanced rectal cancer. This risk stratification, based on baseline clinical staging and tumor response to chemoradiotherapy, has led us to question whether all patients with locally advanced rectal cancer require every component of the multimodal regimen. In this article, we will review recent evidence that some patients with locally advanced rectal cancer can be spared one or more treatment modalities without compromising long-term oncologic outcomes and while preserving quality of life. PMID- 27249691 TI - Gastric Adenocarcinoma: An Update on Genomics, Immune System Modulations, and Targeted Therapy. AB - Gastric adenocarcinoma (GAC) is a global health burden on all societies, and it was the third-leading cause of cancer-related mortality in 2012, causing 723,000 deaths worldwide. The prognosis of patients with metastatic GAC remains poor, with a median overall survival of less than 1 year in patients treated with currently available therapies. A limited number of therapeutic agents is currently available. Recent additions to the armamentarium include trastuzumab and ramucirumab, which have shown some survival advantage when added to cytotoxic(s). Genomic analyses have defined various genotypes of GACs. The novel genomic knowledge can lead to discovery of novel targets and novel therapeutic agents. In this update, we focus on the current genomic data, targeted therapies including immune system modulators, and expand on HER2/neu testing and the use of agents against this target. Several other facets of GAC and its therapy are not to be included in this review but have been discussed elsewhere. PMID- 27249692 TI - The Evolution of Systemic Therapy in Metastatic Renal Cell Carcinoma. AB - The treatment landscape for renal cell carcinoma (RCC) is a dynamic process that has seen considerable change in recent years. We have seen a rebirth of original breakthroughs with immune checkpoint inhibitors showing promise in patients with treatment-refractory disease. The optimal sequencing of treatments and incorporation of novel therapeutics are actively being investigated and have yet to be determined. The clinical challenges of this evolving treatment paradigm can be attributed to cost considerations, toxicity, and defining endpoints in the management of advanced RCC. As novel therapeutics emerge, finding the optimal treatment regimen for patients will have an increasing focus on patient-centered outcomes and improvement in quality of life in addition to improving survival. PMID- 27249693 TI - Approach to Oligometastatic Prostate Cancer. AB - Oligometastatic prostate cancer has increasingly been recognized as a unique clinical state with therapeutic implications. It has been proposed that patients with oligometastases may have a more indolent course and that outcome may be further improved with metastasis-directed local ablative therapy. In addition, there are differing schools of thoughts regarding whether oligometastases represent isolated lesions-where targeted therapy may render a patient disease free-or whether they coexist with micrometastases, where targeted therapy in addition to systemic therapy is required for maximal clinical impact. As such, the approach to the patient with oligometastatic prostate cancer requires multidisciplinary consideration, with surgery, radiotherapy, and systemic therapy potentially of benefit either singularly or in combination. Indeed, mounting evidence suggests durable disease-free intervals and, in some cases, possibly cure, may be achieved with such a multimodal strategy. However, selecting patients that may benefit most from treatment of oligometastases is an ongoing challenge. Moreover, with the advent of new, highly sensitive imaging technologies, the spectrum based on CT of the abdomen and pelvis and technetium bone scan of localized to oligometastatic to widespread disease has become increasingly blurred. As such, new MRI- and PET-based modalities require validation. As some clinical guidelines advise against routine prostate-specific antigen screening, the possibility of more men presenting with locally advanced or de novo oligometastatic prostate cancer exists; thus, knowing how best to treat these patients may become more relevant at a population level. Ultimately, the arrival of prospective clinical data and better understanding of biology will hopefully further inform how best to treat men with this disease. PMID- 27249694 TI - Emerging Molecular Biomarkers in Advanced Prostate Cancer: Translation to the Clinic. AB - Recent clinical and preclinical studies focused on understanding the molecular landscape of castration-resistant prostate cancer (CRPC) have provided insights into mechanisms of treatment resistance, disease heterogeneity, and potential therapeutic targets. This work has served as a framework for several ongoing clinical studies focused on bringing novel observations into the clinic in the form of tissue, liquid, and imaging biomarkers. Resistance in CRPC typically is driven through reactivation of androgen receptor (AR) signaling, which can occur through AR-activating point mutations, amplification, splice variants (such as AR V7), or other bypass mechanisms. Detection of AR aberrations in the circulation negatively impacts response to subsequent AR-directed therapies such as abiraterone and enzalutamide. Other potentially clinically relevant alterations in CRPC include defects in DNA damage repair (at either the somatic or germline level) in up to 20% of patients (with implications for PARP1 inhibitor therapy), PI3K/PTEN/Akt pathway activation, WNT signaling pathway alterations, cell cycle gene alterations, and less common but potentially targetable alterations involving RAF and FGFR2. Imaging biomarkers that include those focused on incorporating overexpressed androgen-regulated genes/proteins, such as prostate specific membrane antigen (PSMA) and dihydrotestosterone (DHT) in combination with CT, can noninvasively identify patterns of AR-driven distribution of CRPC tumor cells, monitor early metastatic lesions, and potentially capture heterogeneity of response to AR-directed therapies and other therapeutics. This article focuses on the current state of clinical biomarker development and future directions for how they might be implemented into the clinic in the near term to improve risk stratification and treatment selection for patients. PMID- 27249695 TI - Update on Intraperitoneal Chemotherapy for the Treatment of Epithelial Ovarian Cancer. AB - Surgical treatment and chemotherapy administration in women with epithelial ovarian cancer is more controversial today than at any point in the last 3 decades. The use of chemotherapy administered intraperitoneally has been particularly contentious. Three large randomized phase III studies, multiple meta analyses, and now real-world data have demonstrated substantial outcome benefit for the use of chemotherapy administered intraperitoneally versus intravenously for first-line postoperative treatment of optimally debulked advanced ovarian cancer. Unfortunately, for each of these randomized studies, there was scope to either criticize the design or otherwise refute adoption of this route of administration. As a result, the uptake has been variable in North America, although in Europe it has been practically nonexistent. Reasons for this include unquestionable additional toxicity, more inconvenience, and extra cost. However, 10-year follow up of these studies demonstrates unprecedented survival in the intraperitoneal arm (median survival 110 months in patients with completely debulked stage III), raising the possibility that by combining maximal debulking surgery with postoperative intraperitoneal chemotherapy it may be possible to bring about a step change in the outcomes for these patients. In this review, we discuss the rationale for administering chemotherapy intraperitoneally, the merits of the main randomized clinical trials, the evidence regarding optimal regimes, issues of toxicity, port considerations, and reasons for lack of universal adoption. We also explore potential clinical and biologic factors that may be useful for patient selection in the future. PMID- 27249696 TI - Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues.... AB - Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies. PMID- 27249697 TI - Treatment of Older Women With Endometrial Cancer: Improving Outcomes With Personalized Care. AB - Endometrial cancer is the most common gynecologic cancer, and with a median age of 62 at diagnosis, it affects a significant number of older women. With increasing age and obesity rates in the world's population, there is an anticipated concomitant increase in older women with endometrial cancer. Older women are more likely to die of endometrial cancer compared with younger patients. Reasons for this include more aggressive tumor biology, less favorable clinicopathologic features, and more advanced disease. Other factors, however, such as reluctance to offer surgical treatment to the older patient and increased complications of treatment are likely to be important. Management of endometrial cancer requires multidisciplinary care (surgery, radiation therapy, and systemic therapy). For each treatment, the feasibility (related to technical aspect of the procedure/treatment), side effects and safety (related to older-patient factors), and the overall benefit as it pertains to older women with endometrial cancer should be assessed carefully with a multidisciplinary approach. Despite the importance of these issues, the data are limited to answer these issues with clarity. In this article, we will review each treatment modality for older women with endometrial cancer. We will introduce the components of comprehensive geriatric assessment and their practical implication for older women with cancer in general and older women with endometrial cancer specifically. PMID- 27249698 TI - What's New in Head and Neck Cancer: Key Findings in 2015-2016 From ECCO/ESMO, ASTRO, and the Multidisciplinary Head and Neck Cancer Symposium. AB - Scientific investigation is extremely active in the treatment, management, and optimization of therapies for patients with head and neck cancer. These issues have undergone recent rapid evolution in response to a changing epidemiology based on an increasing proportion of HPV-associated oropharyngeal cancer with advances in multimodality technologies to improve outcomes and reduce toxicity. Choices of definitive treatment of various anatomic subsites are being refined, balancing the relative indications and advantages of surgery or chemoradiation based strategies. The major potential influence of HPV-associated etiology on therapy selection, prognostic factors, response to treatment, survival outcomes, and post-treatment surveillance has created a robust and distinct field of scientific inquiry around this patient subset. Meanwhile, for patient subsets where prognosis remains poor, therapeutic intensification is being explored, and for recurrent/metastatic disease, improved selection for salvage and novel systemic therapies are under development. For all patients with head and neck cancer, upholding principles of equity and access to the highly specialized care that results in optimal outcomes should be the goal. PMID- 27249700 TI - Using Technology to Improve Cancer Care: Social Media, Wearables, and Electronic Health Records. AB - Digital engagement has become pervasive in the delivery of cancer care. Internet- and cellular phone-based tools and systems are allowing large groups of people to engage with each other and share information. Health systems and individual health professionals are adapting to this revolution in consumer and patient behavior by developing ways to incorporate the benefits of technology for the purpose of improving the quality of medical care. One example is the use of social media platforms by oncologists to foster interaction with each other and to participate with the lay public in dialogue about science, medicine, and cancer care. In addition, consumer devices and sensors (wearables) have provided a new, growing dimension of digital engagement and another layer of patient generated health data to foster better care and research. Finally, electronic health records have become the new standard for oncology care delivery, bringing new opportunities to measure quality in real time and follow practice patterns, as well as new challenges as providers and patients seek ways to integrate this technology along with other forms of digital engagement to produce more satisfaction in the process of care along with measurably better outcomes. PMID- 27249701 TI - Moving Beyond Autologous Transplantation in Multiple Myeloma: Consolidation, Maintenance, Allogeneic Transplant, and Immune Therapy. AB - For multiple myeloma, introduction of novel agents as part of the front-line treatment followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) induces deep responses in a majority of patients with this disease. However, disease relapse is inevitable, and, with each relapse, the remission duration becomes shorter, ultimately leading to a refractory disease. Consolidation and maintenance strategy after ASCT is one route to provide sustained disease control and prevent repeated relapses. Though the consolidation strategy remains largely confined to clinical trials, significant data support the efficacy of consolidation in improving the depth of response and outcomes. There are also increasing rates of minimal residual disease-negativity with additional consolidation therapy. On the other hand, maintenance with novel agents post-transplant is well established and has been shown to improve both progression-free and overall survival. Evolving paradigms in maintenance include the use of newer proteasome inhibitors, immunotherapy maintenance, and patient specific maintenance-a concept that utilizes minimal residual disease as the primary driver of decisions regarding starting or continuing maintenance therapy. The other approach to overcome residual disease is immune therapeutic strategies. The demonstration of myeloma-specific alloimmunity from allogeneic transplantation is well established. More sophisticated and promising immune approaches include adoptive cellular therapies, tumor vaccines, and immune checkpoint manipulations. In the future, personalized minimal residual disease driven treatment strategies following ASCT will help overcome the residual disease, restore multiple myeloma-specific immunity, and achieve sustained disease control while minimizing the risk of overtreatment. PMID- 27249699 TI - The Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies. AB - Fewer than one in 20 adult patients with cancer enroll in cancer clinical trials. Although barriers to trial participation have been the subject of frequent study, the rate of trial participation has not changed substantially over time. Barriers to trial participation are structural, clinical, and attitudinal, and they differ according to demographic and socioeconomic factors. In this article, we characterize the nature of cancer clinical trial barriers, and we consider global and local strategies for reducing barriers. We also consider the specific case of adolescents with cancer and show that the low rate of trial enrollment in this age group strongly correlates with limited improvements in cancer population outcomes compared with other age groups. Our analysis suggests that a clinical trial system that enrolls patients at a higher rate produces treatment advances at a faster rate and corresponding improvements in cancer population outcomes. Viewed in this light, the issue of clinical trial enrollment is foundational, lying at the heart of the cancer clinical trial endeavor. Fewer barriers to trial participation would enable trials to be completed more quickly and would improve the generalizability of trial results. Moreover, increased accrual to trials is important for patients, because trials provide patients the opportunity to receive the newest treatments. In an era of increasing emphasis on a treatment decision-making process that incorporates the patient perspective, the opportunity for patients to choose trial participation for their care is vital. PMID- 27249702 TI - Lung Cancer Screening, Cancer Treatment, and Addressing the Continuum of Health Risks Caused by Tobacco. AB - Tobacco use is the largest preventable risk factor for the development of several cancers, and continued tobacco use by patients with cancer and survivors of cancer causes adverse outcomes. Worldwide tobacco control efforts have reduced tobacco use and improved health outcomes in many countries, but several countries continue to suffer from increased tobacco use and associated adverse health effects. Continued tobacco use by patients undergoing cancer screening or treatment results in continued risk for cancer-related and noncancer-related health conditions. Although integrating tobacco assessment and cessation support into lung cancer screening and cancer care is well justified and feasible, most patients with cancer unfortunately do not receive evidence-based tobacco cessation support. Combining evidence-based methods of treating tobacco addiction, such as behavioral counseling and pharmacotherapy, with practical clinical considerations in the setting of lung cancer screening and cancer treatment should result in substantial improvements in access to evidence-based care and resultant improvements in health risks and cancer treatment outcomes. PMID- 27249703 TI - The Cancer Survivorship Journey: Models of Care, Disparities, Barriers, and Future Directions. AB - Although the number of long-term cancer survivors has increased substantially over past years, the journey of survivorship does not always include high quality, patient-centered care. A variety of survivorship care models have evolved based on who provides this care, the survivor population, the site of care, and/or the capacity for delivering specific services. Other areas of survivorship care being explored include how long follow-up care is needed, application of a risk-based approach to survivorship care, and the role of the survivor in his or her own recovery. However, there is little evidence indicating whether any models improve clinical or patient-reported outcomes. A newer focus in survivorship care has included assessment of potential disparities; the sociodemographic characteristics of population subgroups associated with barriers to receiving high-quality cancer treatment may also affect the survivorship period. Developing policies and programs to address disparities in survivorship care is not simple, and examining how financial hardship affects cancer outcomes, reducing economic barriers to care, and increasing incorporation of patient centered strategies may be important components. Here too, there is little evidence regarding the best strategies to address these disparities. Barriers to providing high-quality, patient-centered survivorship care include lack of evidence, lack of a trained survivorship workforce, lack of reimbursement structures/insurance coverage, and lack of a health care system that reduces fragmented care. Future research needs to focus on developing a survivorship care evidence base, exploring strategies to facilitate provision of survivorship care, and disseminating best survivorship care practices to diverse and international audiences. PMID- 27249704 TI - Developing High-Quality Cancer Rehabilitation Programs: A Timely Need. AB - The number of survivors of cancer in the United States, already 14.5 million, is growing with improved cancer treatment and aging of the population. Two-thirds of cancer survivors will be older than age 65 and are likely to enter cancer treatment already deconditioned and with multiple comorbidities. Survivors of cancer face numerous adverse consequences of cancer treatment that add to or exacerbate the effects of existing comorbidities and increase risk of functional decline. Many of these problems are amenable to rehabilitation interventions, but referral to cancer rehabilitation professionals is not a standard part of care. We present an expanded prospective model of surveillance, cancer rehabilitation assessment, and referral efforts using a multidisciplinary team approach. In this model, cancer rehabilitation begins at the time of cancer diagnosis and continues through and beyond cancer treatment. Physical impairments and psychosocial symptoms are assessed and treated, and lifestyle and exercise interventions are provided to optimize functioning, health, and quality of life. We present a stepped-care framework to guide decisions on when, how, and where to refer survivors to cancer rehabilitation specialists depending on safety requirements and needs. This model has the potential to result in early identification of symptoms and impairments, appropriate referral and timely treatment, and, in turn, will better address and minimize both acute and long-term cancer morbidity. PMID- 27249705 TI - The Advantages and Challenges of Testing Children for Heritable Predisposition to Cancer. AB - The increased application of germline genetic testing is expanding our understanding of the risk factors associated with childhood cancer development, and, in some cases, such testing is also informing clinical management. Nonetheless, the incorporation of genetic testing into the pediatric oncology setting is complex and associated with many ethical and practical challenges. The decision as to whether to pursue clinical genetic testing for hereditary cancer predisposition for children should always be guided by the best interest of the child. Despite this fundamental ethical principle, patients, parents, and health care providers may differ in their opinions. Clinical genetic testing to detect the presence of predisposition syndromes associated with childhood-onset cancers, particularly those for which surveillance and preventive measures have proven to enhance outcome, is currently well accepted. On the other hand, clinical genetic testing of children for syndromes associated with adult-onset cancers has raised many concerns about the potential for psychological harm and disrespect of patient autonomy. As a consequence, such testing is not encouraged. The challenges surrounding germline genetic testing are further complicated when testing is done in the research setting and/or when it involves whole-exome or whole-genome sequencing approaches, which can uncover genetic variants that may or may not be associated with the disease under study. Accordingly, there is great debate around these processes and the most appropriate approaches regarding the return of test results. Future research is needed to enhance knowledge about how best to incorporate genomic information into clinical practice. PMID- 27249706 TI - Addressing Burnout in Oncology: Why Cancer Care Clinicians Are At Risk, What Individuals Can Do, and How Organizations Can Respond. AB - Despite their benevolent care of others, today, more than ever, the cancer care professional who experiences overwhelming feelings of exhaustion, cynicism, and inefficacy is in grave jeopardy of developing burnout. Clinicians are repeatedly physically and emotionally exposed to exceedingly long hours in direct care with seriously ill patients/families, limited autonomy over daily responsibilities, endless electronic documentation, and a shifting medical landscape. The physical and emotional well-being of the cancer care clinician is critical to the impact on quality care, patient satisfaction, and overall success of their organizations. The prevention of burnout as well as targeting established burnout need to be proactively addressed at the individual level and organizational level. In fact, confronting burnout and promoting wellness are the shared responsibility of both oncology clinicians and their organizations. From an individual perspective, oncology clinicians must be empowered to play a crucial role in enhancing their own wellness by identification of burnout symptoms in both themselves and their colleagues, learning resilience strategies (e.g., mindful self-compassion), and cultivating positive relationships with fellow clinician colleagues. At the organizational level, leadership must recognize the importance of oncology clinician well-being; engage leaders and physicians in collaborative action planning, improve overall practice environment, and provide institutional wellness resources to physicians. These effective individual and organizational interventions are crucial for the prevention and improvement of overall clinician wellness and must be widely and systematically integrated into oncology care. PMID- 27249707 TI - Immunotherapy for Soft Tissue Sarcoma: Tomorrow Is Only a Day Away. AB - Despite the advances taking place for patients with many types of cancer, to date there has been little success in meeting the great need for novel treatments of advanced soft tissue sarcoma with effective immunologic therapies. Here, we review recent clinical and preclinical data that indicate immune responses against sarcomas occur spontaneously and can also be successfully provoked. Efforts to manipulate the sarcoma immune microenvironment have the potential to eradicate disease and may also sensitize tumors to other tumor-targeted immunotherapeutic approaches. Other approaches, including vaccines and genetic engineering of T cells, offer a promising opportunity to actively direct cytotoxic lymphocytes toward antigen-bearing sarcomas. Drawing parallels with recent advances made in other cancer types, we identify ways in which sarcomas can be included in the ongoing immunotherapy revolution. PMID- 27249708 TI - Considerations for Implementation of Cancer Molecular Diagnostics Into Clinical Care. AB - Physicians have provided personalized care with as much precision as possible for several centuries. However, increasingly sophisticated understanding of the human genome and of cancer biology has permitted identification of genetic and phenotypic distinctions that might permit development of new tumor biomarker tests for risk categorization, screening, differential diagnosis, prognosis, prediction, and monitoring. Both commercial and academic laboratories are offering tests for single analytes, panels of tests of single analytes, multiparameter assays coalesced into a signature, and total genomic, transcriptomic, or proteomic analyses. However, the absence of a consistent regulatory environment has led to marketing of assays without proven analytic validity or clinical utility. U.S. Food and Drug Administration (FDA) approval or clearance does not necessarily imply that use of the test will improve patient outcomes, and FDA discretion to permit laboratory-developed tests results in unknown benefit, or harm, of others. In this regard, a "bad tumor marker is as bad as a bad drug." Caveat emptor is not a satisfactory approach to delivering high-quality care. Rather, adoption of tumor biomarker tests should be based on high levels of evidence generated in scientifically rigorous studies that demonstrate both analytical validity and clinical utility. Doing so will ensure that clinicians and patients are confident that a tumor biomarker test is likely to improve their outcomes. PMID- 27249709 TI - Basic Overview of Current Immunotherapy Approaches in Cancer. AB - Recent success of immunotherapy strategies such as immune checkpoint blockade in several malignancies has established the role of immunotherapy in the treatment of cancer. Cancers use multiple mechanisms to co-opt the host-tumor immune interactions, leading to immune evasion. Our understanding of the host-tumor interactions has evolved over the past few years and led to various promising new therapeutic strategies. This article will focus on the basic principles of immunotherapy, novel pathways/agents, and combinatorial immunotherapies. PMID- 27249710 TI - Why the Quality Oncology Practice Initiative Matters: It's Not Just About Cost. AB - The nature and cost of cancer care is evolving, affecting more patients and often involving expensive treatment options. The upward cost trends also coincide with a national landscape of increasing regulatory mandates that may demand improved outcomes and value, but that often require significant up-front investment in infrastructure to achieve safety and quality. Oncology practices participating in the American Society of Clinical Oncology (ASCO) Institute for Quality's Quality Oncology Practice Initiative (QOPI) and the QOPI Certification Program (QCP) continue to grow in number and reflect changing demographics of the provision of cancer care. QOPI and QCP benchmarking can be used to achieve quality improvement and to build collaborative quality communities. These programs may be useful tools for oncology practices to comply with new legislation such as the Medicare Access and CHIP Reauthorization Act (MACRA). PMID- 27249711 TI - The Oncology Care Model: A Critique. AB - Rapidly increasing national health care expenditures are a major area of concern as threats to the integrity of the health care system. Significant increases in the cost of care for patients with cancer are driven by numerous factors, most importantly the cost of hospital care and escalating pharmaceutical costs. The current fee-for-service system (FFS) has been identified as a potential driver of the increasing cost of care, and multiple stakeholders are interested in replacing FFS with a system that improves the quality of care while at the same time reducing cost. Several models have been piloted, including a Center for Medicare & Medicaid Innovation (CMMI)-sponsored medical home model (COME HOME) for patients with solid tumors that was able to generate savings by integrating a phone triage system, pathways, and seamless patient care 7 days a week to reduce overall cost of care, mostly by decreasing patient admissions to hospitals and referrals to emergency departments. CMMI is now launching a new pilot model, the Oncology Care Model (OCM), which differs from COME HOME in several important ways. It does not abolish FFS but provides an additional payment in 6-month increments for each patient on active cancer treatment. It also allows practices to participate in savings if they can decrease the overall cost of care, to include all chemotherapy and supportive care drugs, and fulfill certain quality metrics. A critical discussion of the proposed model, which is scheduled to start in 2016, will be provided at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting with practicing oncologists and a Centers for Medicare & Medicaid Services (CMS) representative. PMID- 27249712 TI - Strategies for Sustainable Cancer Care. AB - There is an increasing focus on the relative cost-effectiveness and sustainability of delivering high-quality cancer care, with most emphasis, debatably, given to cost control of innovative treatments. It is difficult to calculate all the direct and indirect contributors to the total cost of cancer treatment, but it is estimated that cancer drugs constitute 10% to 30% of the total cost of cancer care. A 2007 study in France showed the contribution of drug costs was less than 20%, with approximately 70% of the total expenditure on cancer accounted for by health care resource use, such as hospitalization. The U.K. government established the National Institute for Health and Care Excellence (NICE)-the dominant function of which is technology appraisal-to assess the clinical and cost-effectiveness of new pharmaceutical and biopharmaceutical products. This is to ensure that all National Health Service (NHS) patients have equitable access to the most clinically effective and cost-effective treatments that are viable. NICE has developed a transparent, public process to judge incremental cost-effectiveness using the quality-adjusted life year (QALY), which allows comparisons of cost-effectiveness across medical specialties. NICE has been both lauded and criticized-especially when it passes judgment on marginally effective but expensive anticancer drugs-but it provides a route to "rational rationing" and, therefore, may contribute to sustainable cancer care by highlighting the issue of affordable medicine. This implies a challenge to the wider oncology community as to how we might cooperate to introduce the concept of value-driven cancer care. PMID- 27249713 TI - Immune Checkpoint Inhibitors in Brain Metastases: From Biology to Treatment. AB - Cancer immunotherapy has been a subject of intense research over the last several years, leading to new approaches for modulation of the immune system to treat malignancies. Immune checkpoint inhibitors (anti-CLTA-4 antibodies and anti-PD 1/PD-L1 antibodies) potentiate the host's own antitumor immune response. These immune checkpoint inhibitors have shown impressive clinical efficacy in advanced melanoma, metastatic kidney cancer, and metastatic non-small cell lung cancer (NSCLC)-all malignancies that frequently cause brain metastases. The immune response in the brain is highly regulated, challenging the treatment of brain metastases with immune-modulatory therapies. The immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes in certain patients and, therefore, may serve as a potential treatment target. However, clinical data of the efficacy of immune checkpoint inhibitors in brain metastases compared with extracranial metastases are limited, as most clinical trials with these new agents excluded patients with active brain metastases. In this article, we review the current scientific evidence of brain metastases biology with specific emphasis on inflammatory tumor microenvironment and the evolving state of clinical application of immune checkpoint inhibitors for patients with brain metastases. PMID- 27249714 TI - Targeted Therapy in Brain Metastases: Ready for Primetime? AB - Brain metastasis is a serious complication of cancer that causes significant morbidity for patients. Over the last decade, numerous new driver somatic mutations have been recognized and targeted therapies are changing the landscape of treatment in lung cancer, breast cancer, and melanoma, which are also the three most common cancers that result in brain metastases. The common actionable mutations include the EGFR mutation and anaplastic lymphoma kinase (ALK) translocations in non-small cell lung cancer, the HER2 mutation in breast cancer, and the BRAF mutation in melanoma. However, most of the early trials with targeted agents excluded patients with brain metastases. With a better understanding of the biology, several recent trials of targeted therapy that focus on brain metastases have been reported and others are ongoing. Novel agents with better penetration across the blood-brain barrier are currently being investigated for patients with brain metastases. In this review, we discuss the current state of use and future directions of targeted therapies in brain metastases. PMID- 27249715 TI - Current State of Immune-Based Therapies for Glioblastoma. AB - Glioblastoma is one of the most aggressive solid tumors, and, despite treatment options such as surgery, radiation, and chemotherapy, its prognosis remains grim. Novel approaches are needed to improve survival. Immunotherapy has proven efficacy for melanoma, lung cancer, and kidney cancer and is now a focus for glioblastoma. In this article, glioblastoma-mediated immunosuppression will be discussed and two exciting immune approaches, checkpoint inhibitors and viral based therapies, will be reviewed. PMID- 27249716 TI - Tumor Evolutionary Principles: How Intratumor Heterogeneity Influences Cancer Treatment and Outcome. AB - Recent studies have shown that intratumor heterogeneity contributes to drug resistance in advanced disease. Intratumor heterogeneity may foster the selection of a resistant subclone, sometimes detectable prior to treatment. Next-generation sequencing is enabling the phylogenetic reconstruction of a cancer's life history and has revealed different modes of cancer evolution. These studies have shown that cancer evolution is not always stochastic and has certain constraints. Consideration of cancer evolution may enable the better design of clinical trials and cancer therapeutics. In this review, we summarize the different modes of cancer evolution and how this might impact clinical outcomes. Furthermore, we will discuss several therapeutic strategies for managing emergent intratumor heterogeneity. PMID- 27249717 TI - Biosimilars: Here and Now. AB - Congress passed the Biologics Price Competition and Innovation Act (BPCI Act) as part of the Affordable Care Act on March 23, 2010. The BPCI Act authorized an approval pathway for biosimilar and interchangeable products. It defines biosimilarity to mean "that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components" and that "there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency of the product." The biosimilar pathway has the potential to facilitate access to biologic products through increased competition, in the same manner as biosimilars have done for almost 10 years in Europe. The goal of a biosimilar program is not to independently establish safety and effectiveness for each condition of use. Rather, the goal is to demonstrate biosimilarity through an extensive analytical characterization and a targeted clinical program designed to assess for clinically meaningful differences, if they exist. The regulatory approaches in both the United States and Europe involve a totality-of-the evidence approach to demonstrate biosimilarity. Importantly, the biosimilar pathway allows for extrapolation of data across indications so that a sponsor, with adequate scientific justification, need not conduct clinical studies in each intended condition of use. Without extrapolation, development may not be feasible for many products, and patients and resources could be diverted from clinical studies of newer agents for cancer. PMID- 27249718 TI - Arming the Immune System Through Vaccination to Prevent Cancer Recurrence. AB - Cancer vaccines have the potential to provide a nontoxic treatment for the prevention of cancer recurrence in the adjuvant setting. Many cancer vaccines have been tested in multiple phase III trials with minimal success. However, through these failed clinical trials, we have learned that the ideal setting for vaccine therapy is the adjuvant setting. Also, we have learned important lessons about patient selection to maximize the probability of success. This article will highlight some of the successes, our trial results in the adjuvant setting, and future directions. PMID- 27249719 TI - The Role of Nephrectomy for Kidney Cancer in the Era of Targeted and Immune Therapies. AB - Although two phase III trials support the recommendation of nephrectomy followed by interferon alpha in metastatic renal cell carcinoma (RCC), this procedure cannot be applied to every patient with this condition. Systemic therapy has changed from interferon alpha to antiangiogenic-targeted therapy, and the clinical impact of nephrectomy in the era of targeted therapy has not been proven. The SEER database shows that only 35% of patients with advanced RCC undergo nephrectomy as their initial treatment. Retrospective studies showed improved overall survival (OS) outcomes with nephrectomy and interleukin-2 (IL-2) therapy; however, the inherent selection bias of younger and healthier patients receiving IL-2 likely accounts for this finding. Neoadjuvant therapy has demonstrated only modest efficacy in unresectable disease, and if remission is obtained with systemic therapy, it is unclear whether nephrectomy has any incremental benefit. In the absence of proven benefit of nephrectomy in the setting of targeted therapy, it seems advisable for patients with RCC with severely symptomatic disease, competing comorbidities, poor performance status, or unresectable disease to avoid nephrectomy and proceed directly to systemic therapy. The clinical implications of deferred cytoreductive nephrectomy for patients with metastatic RCC are poorly understood, and patient cohorts that do not undergo this procedure are likely to be comprised of patients with unfavorable disease characteristics. Unfortunately, the completed trials of targeted therapy were 90% comprised of patients with prior nephrectomy (the majority of trials incorporate prior nephrectomy as an eligibility requirement) and hence may not reflect the outcomes of the majority of the patients with advanced RCC who have not undergone nephrectomy. Newer therapies such as nivolumab and cabozantinib have also been evaluated for a population in which 90% of the patients underwent nephrectomy. Future clinical trials and registry studies must focus on the therapeutic treatment and overall outcome of patients without nephrectomy and treated with contemporary systemic therapy. PMID- 27249720 TI - Overcoming Therapeutic Resistance by Targeting Cancer Inflammation. AB - Tumor-infiltrating myeloid cells are a prominent feature of most solid malignancies. This inflammatory immune response, driven by tumor-intrinsic signaling pathways, is a major checkpoint to therapeutic efficacy achieved with immunotherapy and standard cytotoxic therapies. To overcome therapeutic resistance mediated by cancer inflammation, ongoing clinical trials are evaluating strategies that (1) deplete myeloid cells from tumors, (2) inhibit tumor-promoting properties of myeloid cells, and (3) redirect myeloid cells with tumor-inhibitory activity. PMID- 27249721 TI - Pharmacogenomics, Pharmacokinetics, and Pharmacodynamics in the Era of Targeted Therapies. AB - The complex nature of the pharmacologic aspects of cancer therapeutics has become more apparent in the past several years with the arrival of a cascade of target based agents and the difficult challenge of bringing individualized precision medicine to oncology. Interpatient variability in drug action, singularly in novel agents, is in part caused by pharmacogenomic (PG), pharmacokinetic, and pharmacodynamic (PD) factors, and drug selection and dosing should take this into consideration to optimize the benefit for our patients in terms of antitumor activity and treatment tolerance. In this regard, somatic genetic evaluation of tumors is useful in not only predicting response to initial targeted therapies but also in anticipating and guiding therapy after the development of acquired resistance; therapeutic drug monitoring of novel small molecules and monoclonal antibodies must be incorporated in our day-to-day practice to minimize the negative effect on clinical outcome of interindividual variability on pharmacokinetic processes of these drugs for all patients, but especially for fragile patient populations and those with organ dysfunction or comorbidities. For these populations, incorporating frailty assessment tools into trials of newer agents and validating frailty-based dose adjustment should be an important part of further drug development. PMID- 27249722 TI - Liver Metastases in Colorectal Cancer. AB - Resection of colorectal liver metastases is a treatment standard because patients experience long-term disease-free survival or are even cured after undergoing this procedure. Improved surgical techniques for liver resection in combination with downsizing liver metastases by chemotherapy, interventions to induce liver hypertrophy before resection, and the use of ablative techniques have allowed us to expand the indications for liver surgery and local treatment in situations with limited metastatic colorectal cancer. Resectability and identification of patients who might benefit from liver surgery and local ablative techniques are key factors for the treatment of patients with colorectal cancer. Despite the wide acceptance of liver surgery and ablative techniques, there are many open questions on the management of limited metastatic disease, such as which patients benefit from an aggressive surgical approach, what the indications for ablative and other local techniques are, and what the role of chemotherapy is for patients with resectable or resected disease. Unfortunately, results of randomized trials are only available for a limited number of these questions. PMID- 27249723 TI - Biliary Tract Cancer: Epidemiology, Radiotherapy, and Molecular Profiling. AB - Biliary tract cancer, or cholangiocarcinoma, arises from the biliary epithelium of the small ducts in the periphery of the liver (intrahepatic) and the main ducts of the hilum (extrahepatic), extending into the gallbladder. The incidence and epidemiology of biliary tract cancer are fluid and complex. It is shown that intrahepatic cholangiocarcinoma is on the rise in the Western world, and gallbladder cancer is on the decline. Radiation therapy has emerged as an important component of adjuvant therapy for resected disease and definitive therapy for locally advanced disease. The emerging sophisticated techniques of imaging tumors and conformal dose delivery are expanding the indications for radiotherapy in the management of bile duct tumors. As we understand more about the molecular pathways driving biliary tract cancers, targeted therapies are at the forefront of new therapeutic combinations. Understanding the gene expression profile and mutational burden in biliary tract cancer allows us to better discern the pathogenesis and identify promising new developmental therapeutic targets. PMID- 27249724 TI - Compassionate Use: A Modest Proposal. PMID- 27249725 TI - The Past, Present, and Future of Pancreatic Cancer Clinical Trials. AB - Upper gastrointestinal malignancies comprise half of the deadliest cancers as defined by those with a 5-year survival rate less than 50%. Using pancreatic adenocarcinoma (PAC) as an example, we retrospectively evaluated the success of phase III clinical trials, examined the current landscape of clinical trials, and identified emerging areas that foretell the future for this disease. Pancreatic and liver cancers are on the rise and will be the second and third leading causes of cancer deaths in 2030. A total of 35 different agents or combinations have been tested in randomized phase III clinical trials for patients with advanced PAC over the past 25 years, but only 11% have been incorporated into clinical practice. There has been a 37% increase in the number of PAC trials open in the United States between 2011 to 2012 and 2014 to 2015. Enrollment has also increased slightly, from 3.85% of the newly diagnosed cases in 2011 to 4.15% in 2014. However, the demand for patients far exceeds the number of patients available for these trials. On the horizon is the realization that stratification of patients with PAC using biomarkers that predict a high probability of a response could reallocate patients to faster, smaller trials with a greater chance of a survival benefit. The current landscape of PAC clinical trials and the launch of the Pancreatic Cancer Action Network's Know Your Tumor initiative indicate this shift is starting to occur, with particular emphasis on targeted therapies, immunotherapies, and agents that disrupt the stroma. PMID- 27249726 TI - Localized Pancreatic Cancer: Multidisciplinary Management. AB - Pancreatic cancer is an aggressive cancer that continues to have single-digit 5 year mortality rates despite advancements in the field. Surgery remains the only curative treatment; however, most patients present with late-stage disease deemed unresectable, either due to extensive local vascular involvement or the presence of distant metastasis. Resection guidelines that include a borderline resectable group, as well as advancements in neoadjuvant chemotherapy and radiation that improve resectability of locally advanced disease, may improve outcomes for patients with more invasive disease. Multi-agent chemotherapy regimens fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and nab paclitaxel with gemcitabine improved response rates and survival in metastatic pancreatic cancer and are now being used in earlier stages for patients with localized potentially resectable and unresectable disease, with goals of downstaging tumors to allow margin-negative resection and reducing systemic recurrence. Chemoradiotherapy, although still controversial for both resectable and unresectable pancreatic cancer, is being used in the context of contemporary chemotherapy backbone regimens, and novel radiation techniques such as stereotactic body frame radiation therapy (SBRT) are studied on the premise of maintaining or improving efficacy and reducing treatment duration. Patient selection for optimal treatment designation is currently provided by multidisciplinary tumor boards, but biomarker discovery, in blood, tumors, or through novel imaging, is an area of intense research. Results to date suggest that some patients with unresectable disease at the outset have survival rates as good as those with initially resectable disease if able to undergo surgical resection. Long-term follow-up and improved clinical trials options are needed to determine optimal treatment modalities for patients with localized pancreatic cancer. PMID- 27249727 TI - Issues in Breast Cancer Survivorship: Optimal Care, Bone Health, and Lifestyle Modifications. AB - There are an estimated 3.1 million survivors of breast cancer in the United States. The predominant reasons for this substantially large population are that breast cancer is the most common noncutaneous malignancy among women and that 5 year survival rates after breast cancer treatment are approximately 90%. These patients have many medical considerations, including the need to monitor for disease recurrence and to manage complications of their previous cancer treatments. Most patients remain at risk indefinitely for local and systemic recurrences of their breast cancers and have an increased risk of developing contralateral new primary breast cancers. Therefore, optimizing care for this patient population is critical to the overall health care landscape in the United States. Here, we summarize survivorship care delivery and its challenges, the optimization of bone health in breast cancer survivors, and opportunities for risk reduction through lifestyle modifications. PMID- 27249728 TI - Treatment of Muscle-Invasive Bladder Cancer in Older Patients. AB - Treatment of muscle-invasive bladder cancer in older patients is challenging. Definitive therapy of localized disease requires either surgery or radiation therapy, ideally combined with systemic chemotherapy. However, current population data suggest that less than half of patients older than age 70 are offered such treatments. We will review tools available to assess the fitness of older patients for surgery, alternatives, and tips for perioperative patient treatment. PMID- 27249730 TI - Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer. AB - The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy. PMID- 27249729 TI - Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools. AB - Active surveillance (AS) has emerged as a standard management option for men with very low-risk and low-risk prostate cancer, and contemporary data indicate that use of AS is increasing in the United States and abroad. In the favorable-risk population, reports from multiple prospective cohorts indicate a less than 1% likelihood of metastatic disease and prostate cancer-specific mortality over intermediate-term follow-up (median 5-6 years). Higher-risk men participating in AS appear to be at increased risk of adverse outcomes, but these populations have not been adequately studied to this point. Although monitoring on AS largely relies on serial prostate biopsy, a procedure associated with considerable morbidity, there is a need for improved diagnostic tools for patient selection and monitoring. Revisions from the 2014 International Society of Urologic Pathology consensus conference have yielded a more intuitive reporting system and detailed reporting of low-intermediate grade tumors, which should facilitate the practice of AS. Meanwhile, emerging modalities such as multiparametric magnetic resonance imaging and tissue-based molecular testing have shown prognostic value in some populations. At this time, however, these instruments have not been sufficiently studied to consider their routine, standardized use in the AS setting. Future studies should seek to identify those platforms most informative in the AS population and propose a strategy by which promising diagnostic tools can be safely and efficiently incorporated into clinical practice. PMID- 27249731 TI - Gynecologic Cancers: Emerging Novel Strategies for Targeting DNA Repair Deficiency. AB - The presence of a BRCA mutation, somatic or germline, is now established as a standard of care for selecting patients with ovarian cancer for treatment with a PARP inhibitor. During the clinical development of the PARP inhibitor class of agents, a subset of women without BRCA mutations were shown to respond to these drugs (termed "BRCAness"). It was hypothesized that other genetic abnormalities causing a homologous recombinant deficiency (HRD) were sensitizing the BRCA wild type cancers to PARP inhibition. The molecular basis for these other causes of HRD are being defined. They include individual gene defects (e.g., RAD51 mutation, CHEK2 mutation), homozygous somatic loss, and whole genome properties such as genomic scarring. Testing this knowledge is possible when selecting patients to receive molecular therapy targeting DNA repair, not only for patients with ovarian cancer but also endometrial and cervical cancers. The validity of HRD assays and multiple gene sequencing panels to select a broader population of patients for treatment with PARP inhibitor therapy is under evaluation. Other non HRD targets for exploiting DNA repair defects in gynecologic cancers include mismatch repair (MMR), checkpoint signaling, and nonhomologous end-joining (NHEJ) DNA repair. This article describes recent evidence supporting strategies in addition to BRCA mutation for selecting patients for treatment with PARP inhibitor therapy. Additionally, the challenges and opportunities of exploiting DNA repair pathways other than homologous recombination for molecular therapy in gynecologic cancers is discussed. PMID- 27249732 TI - Enhancing Care of the Survivor of Gynecologic Cancer: Managing the Menopause and Radiation Toxicity. AB - It is expected that there will be 290,000 cases of gynecologic cancers in 2016. Of these cancers, 60,000 will be endometrial and 22,000 will be ovarian-the two most common gynecologic cancers. Endometrial and ovarian cancers occur in menopausal women with mean ages of 60 and 63, respectively. The majority of endometrial cancers are early stage, and 5-year survival is considered good at upwards of 75%. For ovarian cancer, while survival rates have improved, the 5 year survival rate for the most common stage (stage III) is 40%. Thus, a substantial number of patients with gynecologic cancer are menopausal, and a significant number of patients are survivors, particularly of endometrial cancers. It will be important for survivors of gynecologic cancers to receive care tailored to their needs as women and to mitigate gender-specific side effects of their cancer treatment. PMID- 27249733 TI - Immunotherapy and Checkpoint Inhibitors in Recurrent and Metastatic Head and Neck Cancer. AB - Immune surveillance is well recognized as an important mechanism to prevent development or progression of head and neck cancers. Head and neck cancer cells can escape the immune system through multiple mechanisms including development of tolerance in T cells and inhibition of T-cell-related pathways, generally referred to as checkpoint inhibitors. This article highlights advances in immuno oncology treatment approaches in recurrent and metastatic head and neck squamous cell carcinoma. Clinical trials are discussed in detail, with an emphasis on response dynamics, oncologic efficacy, safety, and tolerability of checkpoint inhibitors. In addition, developing concepts and ongoing studies in this setting are also reviewed. PMID- 27249734 TI - Locoregional Recurrent or Second Primary Head and Neck Cancer: Management Strategies and Challenges. AB - Treatment of patients with locoregional recurrent or second primary head and neck squamous cell cancer (HNSCC) has been guided by well-reasoned principles and informed by carefully tested chemotherapy and radiation regimens. However, clinical decision making for this population is complicated by many factors. Although surgery is generally considered the treatment of choice for patients with HNSCC with recurrent disease or new second primary disease in a previously irradiated field, operability of cases is not always straightforward. Postoperative treatment is frequently warranted but carries significant risk. In addition, the rapid rise in the incidence of HPV-associated HNSCC raises the question of whether established treatment paradigms should be re-examined in this population of patients with a much better prognosis than the non-HPV population. Furthermore, new radiation techniques and new systemic agents show early promising results in recent clinical studies, suggesting potential for practice changing effects in the future management of this disease. This article examines each of the treatment modalities used in the care of patients with HNSCC with recurrent or new second primary disease and provides a perspective to aid clinicians in the management of this disease. PMID- 27249735 TI - Challenges and Opportunities in Delivering High-Quality Cancer Care: A 2016 Update. AB - Herein, both the rationale and scope of current initiatives aimed at improving the quality of cancer care delivery in the United States are described. First, we discuss a recent report from the Institute of Medicine that issued a strong call for both the development of quality measures in oncology and implementation of a learning health care system in which data and experience from clinical practice can inform continuous improvements in cancer care. Second, we review the multiple, diverse initiatives that are underway to identify, test, and validate quality measures for the entire spectrum of cancer care. Finally, we discuss regional quality improvement collaboratives as one successful approach to creating a cycle of quality measurement, identification of best practices, and implementation of changes in practice patterns that ultimately yield improved care and outcomes for patients with cancer. PMID- 27249736 TI - Evolving Therapies in Acute Myeloid Leukemia: Progress at Last? AB - Acute myeloid leukemia (AML) is an acquired disease characterized by chromosomal translocations and somatic mutations that lead to leukemogenesis. Systemic combination chemotherapy with an anthracycline and cytarabine remains the standard induction regimen for "fit" adults. Patients who achieve complete remission generally receive postinduction therapy with cytarabine-based chemotherapy or an allogeneic bone marrow transplant. Those unfit for induction chemotherapy are treated with hypomethylating agents (HMAs), low-dose cytarabine, or they are offered supportive care alone with transfusions and prophylactic antimicrobials. The revolution in understanding the genetics of AML, facilitated by next-generation sequencing, has led to many new drugs against driver mutations. Better methods of identification of leukemic blasts have provided us with better means to detect the disease left behind after cytotoxic chemotherapy regimens. This measurable residual disease has been correlated with poorer relapse-free survival, demonstrating the need for novel strategies to eradicate it to improve the outcome of patients with acute leukemias. In this article, we discuss adapting and improving AML therapy by age and comorbidities, emerging targeted therapies in AML, and minimal residual disease (MRD) assessment in AML. PMID- 27249737 TI - Tailoring Chemotherapy in Early-Stage Breast Cancer: Based on Tumor Biology or Tumor Burden? AB - The question of whether to offer adjuvant chemotherapy to patients with early stage breast cancer has always been challenging to answer. It is well known that a substantial proportion of patients with early-stage breast cancer are over treated, especially when staging and hormonal and HER2 receptors are solely taken into consideration. The advances in our knowledge of breast cancer biology and its clinical implications were the basis for the discovery of additional reliable prognostic markers to aid decision making for adjuvant treatment. Gene expression profiling is a molecular tool that more precisely defines the intrinsic characteristics of each individual tumor. The application of this technology has led to the development of gene signatures/profiles with relevant prognostic-and some predictive-value that have become important tools in defining which patients with early-stage breast cancer can be safely spared from chemotherapy. However, the exact clinical utility of these tools will only be determined after the results of two large prospective randomized trials, MINDACT and TailorX, evaluating their role become available. Notwithstanding the existence of these genomic tools, tumor burden (defined as tumor size and nodal status) still has independent prognostic value and must be incorporated in decision making. In addition, these gene signatures have limited predictive value, and new biomarkers and new targets are needed. Therefore close collaboration between clinicians and scientists is crucial. Lastly, issues of cost-effectiveness, reimbursement, and availability are crucial and widely variable around the globe. PMID- 27249738 TI - Advances in the Genetics and Therapy of Acute Lymphoblastic Leukemia. AB - Acute lymphoblastic leukemia (ALL) remains an important cause of morbidity in children and adults. In this article, we highlight advances in the genetics and therapy of three key subtypes of ALL: T-cell ALL, BCR-ABL1 (Philadelphia [Ph] chromosone-positive), and Ph-like ALL. T-ALL is an aggressive disease that accounts for about 15% and 25% of ALL among pediatric and adult cohorts, respectively, and exhibits a multistep nature of cancer initiation and progression. The integration of cytogenetics, molecular biology, and immunophenotype analyses has led to the identification of defined T-ALL subgroups, such as early T-cell precursor ALL and novel lesions with a prognostic role, for which specific inhibitors are being developed. Ph-positive ALL was historically regarded as a subtype of ALL with a poor prognosis, and allogeneic stem cell transplant was recommended for all patients who could undergo this procedure. The deep complete responses seen with combination tyrosine kinase inhibitors (TKIs) and chemotherapy in Ph-positive ALL, and the reports of long term survival among some patients not undergoing allogeneic stem cell transplant, has raised the question of whether there is a subset of patients who could be cured without this intervention. Ph-like ALL is a subtype of B-progenitor ALL common among older children and adults and associated with a diverse range of genetic alterations that activate kinase signaling. Ph-like ALL is also associated with poor outcome, for which precision medicine trials identifying kinase alterations and testing TKI therapy are being developed. PMID- 27249739 TI - Individualizing Care for Patients With Myeloproliferative Neoplasms: Integrating Genetics, Evolving Therapies, and Patient-Specific Disease Burden. AB - Individualized medicine is important for patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera, and myelofibrosis, which are heterogeneous in terms of genetic mutation profile, prognosis, disease burden, and symptoms. Status of MPN driver mutations in JAK2, CALR, and MPL (or lack of one of these mutations) and other myeloid mutations (ASXL1, SRSF2, CBL, and IDH1/2, among others) affects diagnosis and prognosis. Management begins with estimating the prognosis, disease burden including MPN symptoms, and prevention of vascular events. Allogeneic stem cell transplantation is the definitive therapy in a subset of patients with myelofibrosis, the majority of whom receive JAK inhibition with ruxolitinib to relieve splenomegaly and symptoms and to prolong survival. Ruxolitinib is now a second-line therapy in polycythemia vera, with pegylated interferon being evaluated as a potential front line therapy compared with hydroxyurea. The therapeutic landscape is evolving to include new JAK inhibitors, which may affect cytopenias (pacritinib and momelotinib), combination therapies including ruxolitinib, and novel targets such as pentraxin and telomerase. Assessing the therapeutic efficacy (including symptom impact) and toxicity of these new approaches is necessary to determine longitudinal management of MPNs in clinical practice and is a key component of "individualizing" care for patients with MPNs. PMID- 27249740 TI - Integrating Frailty, Comorbidity, and Quality of Life in the Management of Myelodysplastic Syndromes. AB - Myelodysplastic syndromes (MDS) are a group of acquired hematopoietic stem cell disorders that manifest with progressive bone marrow failure and have a propensity to transform into leukemia. Although an increase in biologic understanding of MDS has led to improved patient risk stratification and prognostication, advances in treatment have lagged behind. While hematopoietic cell transplantation (HCT) is a potentially curative option for some, most affected patients continue to be treated with supportive care or with drugs that offer temporary palliation such as hematopoietic growth factors, DNA hypomethylating agents, or immunomodulatory therapy. For several groups, such as those with intermediate-risk disease as classified by the Revised International Prognostic Scoring System (IPSS-R) or those with higher-risk disease for whom hypomethylating agents have failed, optimal treatment remains uncertain. Inclusion of patient-related factors such as frailty and comorbid conditions into risk assessment can improve prognostication beyond the disease-associated variables included in systems such as the IPSS-R. This article focuses on approaches to assessing and integrating frailty, comorbidities, and quality of life into the treatment of patients with MDS. PMID- 27249741 TI - Searching for a Light at the End of the Tunnel? Beyond Hypomethylating Agents in Myelodysplastic Syndromes. AB - Hypomethylating agents (HMAs) are the mainstay treatment of patients with myelodysplastic syndromes. Hypomethylating agents remain the only treatment, other than allogeneic hematopoietic stem cell transplantation (AHSCT), that improves overall survival (OS) for patients with higher-risk myelodysplastic syndromes. It is crucial to maximize the benefit of HMAs by selecting the appropriate dosing and schedule and continuing therapy until clear evidence of lack of response or failure of therapy. Strategies to improve outcome with HMAs include identifying tools and biomarkers for better patient selection, namely the ability to identify those who achieve complete response (CR) or long duration of response, combination strategies with HMAs aim to improve response rate or its duration. The outcome of patients with myelodysplastic syndromes after HMA failure is poor for both patients with higher-risk and lower-risk disease and represents an unmet medical need. The best outcomes after HMA failure are reported with AHSCT or novel agents in clinical trials. This article discusses the maximizing benefit of HMAs, offers strategies to improve outcome with HMAs, and, finally, reviews selected novel agents in development after HMA failure. PMID- 27249742 TI - Current Management Concepts: Primary Central Nervous System Lymphoma, Natural Killer T-Cell Lymphoma Nasal Type, and Post-transplant Lymphoproliferative Disorder. AB - Primary central nervous system lymphoma, natural killer T-cell lymphoma nasal type, and post-transplant lymphoproliferative disorder are uncommon and complex lymphoproliferative disorders. These disorders present with different risk factors, have complex tumor characteristics, and require unique therapeutic interventions. These diseases require a multidisciplinary complex team approach. This article will update current management approaches and concepts. PMID- 27249743 TI - Functional Imaging Using 18-Fluorodeoxyglucose PET in the Management of Primary Mediastinal Large B-Cell Lymphoma: The Contributions of the International Extranodal Lymphoma Study Group. AB - Primary mediastinal large B-cell lymphoma (PMLBCL) is recognized as a distinct disease entity. Treatment outcomes appear better than in other diffuse large B cell lymphoma (DLBCL) types, partly because of their earlier stage at presentation and the younger age of most patients. If initial treatment fails, however, the results of salvage chemotherapy and myeloablative treatment are poor. The need to avoid relapses after initial therapy has led to controversy over the extent of front-line therapy, particularly whether consolidation radiotherapy to the mediastinum is always required and whether the 18 fluorodeoxyglucose ((18)F-FDG) uptake detected by PET-CT scan can be used to determine its requirements. Functional imaging using PET-CT generally allows distinguishing of residual mediastinal masses containing active lymphoma from those with only sclerotic material remaining. The International Extranodal Lymphoma Study Group (IELSG) conducted the prospective IELSG-26 study, which showed that a five-point visual scale can be used to define metabolic response after immunochemotherapy and that a cut point based on liver uptake discriminates effectively between high or low risk of failure, with 5-year progression-free survival (PFS) of 99% versus 68% and 5-year overall survival (OS) of 100% versus 83%. This study also showed that a baseline quantitative PET parameter, namely the total lesion glycolysis describing the metabolic tumor burden, can be a powerful predictor of PMLBCL outcomes and warrants further validation as a biomarker. The ongoing IELSG-37 randomized study addresses the need for consolidation mediastinal radiotherapy in patients in whom a complete metabolic response (CMR) can be seen on PET scans after standard immunochemotherapy. PMID- 27249744 TI - Risk-Adapted Treatment of Advanced Hodgkin Lymphoma With PET-CT. AB - Although patients with advanced-stage classic Hodgkin lymphoma have excellent outcomes with contemporary therapy, the outcomes of patients with refractory disease is suboptimal. Identification of these high-risk patients at diagnosis is challenging as the differences in outcomes using clinical criteria are less marked using current modern therapy. Data suggest that an interim PET-CT may be a powerful tool in risk-stratifying patients. Retrospective studies show that a negative interim PET-CT after two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is predictive of favorable outcome independent of IPS score. Currently, there are several ongoing trials that aim to determine whether early-response assessment can be used to select patients who might benefit from modifications of subsequent therapy, either by intensifying or abbreviating regimens and/or omitting radiotherapy with promising early results. Longer follow up is required to assess whether this strategy impacts overall survival (OS). Herein, we review the results of recent trials using interim PET-CT-based adaptive design in the treatment of advanced HL. PMID- 27249745 TI - Chemoimmunotherapy Versus Targeted Treatment in Chronic Lymphocytic Leukemia: When, How Long, How Much, and in Which Combination? AB - During the past 5 years, rapid therapeutic advances have changed the landscape of chronic lymphocytic leukemia (CLL) therapy. This disease has traditionally been treated using cytotoxic chemotherapy regimens in combination with anti-CD20 antibody treatment, and recent long-term follow-up data from multiple centers suggest that fit patients with CLL with favorable disease features-particularly mutated immunoglobulin heavy chain variable region (IGHV) genes-derive very long term benefit from the most potent of these regimens, namely the fludarabine, cyclophosphamide, and rituximab (FCR) regimen. The advent of oral targeted therapies, particularly ibrutinib and idelalisib, has provided generally well tolerated and highly effective additional options that have come into widespread use in the relapsed setting. Additional agents are advancing in clinical development, with the BCL-2 inhibitor venetoclax likely to be approved by the U.S. Food and Drug Administration (FDA) in 2016. With the development of these novel therapies for patients with relapsed CLL, many unanswered questions remain, including the optimal sequence (first vs. second line), duration, discontinuation, and combination of these agents. In addition, recent publications show the emergence of a pattern of treatment resistance in certain subgroups of patients with del(17p) and complex karyotype that needs further study and improvement. Because the field of CLL management has become much more complex, we focus here on understanding the recent data and discuss many of the questions and controversies important for how we approach patients with CLL. PMID- 27249746 TI - Improving Response to Hormone Therapy in Breast Cancer: New Targets, New Therapeutic Options. AB - The majority of breast cancer expresses the estrogen and or progesterone receptors (ER and PR). In tumors without concomitant HER2 amplification, hormone therapy is a major treatment option for all disease stages. Resistance to hormonal therapy is associated with disease recurrence and progression. Recent studies have identified a number of resistance mechanisms leading to estrogen independent growth of hormone receptor-positive (HR+) breast cancer as a result of genetic and epigenetic alterations, which could be exploited as novel therapeutic targets. These include acquired mutations in ER-alpha (ESR1) in response to endocrine deprivation; constitutive activation of cyclin-dependent kinases (CDK) 4 and 6; cross talk between ER and growth factor receptor signaling such as HER family members, fibroblast growth factor receptor (FGFR) pathways, intracellular growth, and survival signals PI3K/Akt/mTOR; and epigenetic modifications by histone deacetylase (HDAC) as well as interactions with tumor microenvironment and host immune response. Inhibitors of these pathways are being developed to improve efficacy of hormonal therapy for treatment of both metastatic and early-stage disease. Two agents are currently approved in the United States for the treatment of metastatic HR+ breast cancer, including the mTOR inhibitor everolimus and the CDK4/6 inhibitor palbociclib. Management of toxicity is a critical aspect of treatment; the primary toxicity of everolimus is stomatitis (treated with topical steroids) and of palbociclib is neutropenia (treated with dose reduction/delay). Many agents are in clinical trials, primarily in combination with hormone therapy; novel combinations are under active investigation. PMID- 27249747 TI - Future Directions in the Evaluation and Treatment of Precursor Plasma Cell Disorders. AB - Multiple myeloma (MM) is an incurable disease that progresses from a premalignant stage termed monoclonal gammopathy of undetermined significance (MGUS) and an intermediate stage of smoldering multiple myeloma (SMM). Recent major advances in therapy with more effective and less toxic treatments have brought reconsideration of early therapeutic intervention in management of SMM, with the goal of reducing progression of the disease before the occurrence of end-organ damage to MM and improving survival. Key to this effort is accurate identification of patients at high risk of progression who would truly benefit from early intervention. In this review, we discuss the current definitions, risk factors, risk stratification, prognosis, and management of MGUS and SMM, as well as new emerging therapeutic options under active investigation. PMID- 27249748 TI - The Role of Imaging in the Treatment of Patients With Multiple Myeloma in 2016. AB - The novel criteria for the diagnosis of symptomatic multiple myeloma have revealed the value of modern imaging for the management of patients with myeloma. Whole-body low-dose CT (LDCT) has increased sensitivity over conventional radiography for the detection of osteolytic lesions, and several myeloma organizations and institutions have suggested that whole-body LDCT should replace conventional radiography for the work-up of patients with myeloma. MRI is the best imaging method for the depiction of marrow infiltration by myeloma cells. Whole-body MRI (or at least MRI of the spine and pelvis if whole-body MRI is not available) should be performed for all patients with smoldering multiple myeloma with no lytic lesions to look for occult disease, which may justify treatment. In addition, MRI accurately illustrates the presence of plasmacytomas, spinal cord, and/or nerve compression for surgical intervention or radiation therapy; it is also recommended for the work-up of solitary bone plasmacytoma, and it may distinguish malignant from benign fractures (which is very important in cases of patients in biochemical remission with no other signs of progression). Diffusion weighted imaging (DWI) seems to improve MRI diagnosis in patients with myeloma. PET/CT is a functional imaging technique, more sensitive than conventional radiography for the detection of lytic lesions, which probably allows better definition of complete response and minimal residual disease compared with all other imaging methods. PET/CT has shown the best results in the follow-up of patients with myeloma and has an independent prognostic value both at diagnosis and following treatment. PET/CT can also be used for the work-up of solitary bone plasmacytoma and nonsecretory myeloma. PMID- 27249749 TI - Updated Diagnostic Criteria and Staging System for Multiple Myeloma. AB - There has been remarkable progress made in the diagnosis and treatment of multiple myeloma (MM). The median survival of the disease has doubled as a result of several new active drugs. These advances have necessitated a revision of the disease definition and staging of MM. Until recently, MM was defined by the presence of end-organ damage, specifically hypercalcemia, renal failure, anemia, and bone lesions (CRAB features) that can be attributed to the clonal process. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria for MM to add three specific biomarkers that can be used to diagnose the disease in patients who did not have CRAB features: clonal bone marrow plasma cells greater than or equal to 60%, serum free light chain (FLC) ratio greater than or equal to 100 provided involved FLC level is 100 mg/L or higher, or more than one focal lesion on MRI. In addition, the definition was revised to allow CT and PET-CT to diagnose MM bone disease. These changes enable early diagnosis and allow the initiation of effective therapy to prevent the development of end-organ damage for patients who are at the highest risk. A new staging system has been developed that incorporates high-risk cytogenetic abnormalities in addition to standard laboratory markers of prognosis. PMID- 27249750 TI - Minimal Residual Disease by Next-Generation Sequencing: Pros and Cons. AB - The wealth of data recently generated highlights that minimal residual disease (MRD)-negative status can be achieved in a large proportion of patients. These studies, in addition to a meta-analysis, clearly suggest significant improvement in both event-free survival (EFS) and overall survival (OS) among those patients achieving MRD-negative status, especially with sensitivity of one cell in 1 million bone marrow cells. There is an evolving consensus that achieving MRD negative status should become the ultimate goal of therapeutic intervention. Further future efforts should now be directed at determining how MRD status can be used to guide and personalize further therapy including type of consolidation and maintenance therapy. PMID- 27249751 TI - New Targets and New Agents in High-Risk Multiple Myeloma. AB - Advances in the treatment of multiple myeloma have resulted in dramatic improvements in outcomes for patients. The newly emerging profiling of mutations emerging as a consequence of large prospective sequencing studies such as the CoMMpass Study or other efforts from European investigators are not further helping to define the place and role for personalized medicine in myeloma. While mutations such as NRAS, KRAS, and BRAF do occur in myeloma, it is not clear that targeting them as a single drug strategy will result in meaningful responses or durations of response. Personalized medicine in multiple myeloma at this time likely entails the use of risk-based approaches for maintenance therapy, the use of current biology-based treatments such as proteasome inhibitors, and immunomodulatory agents, with an eye towards the use of mutation-specific treatments in the setting of minimal residual disease or in concert with biology based treatments overall. PMID- 27249752 TI - Next-Generation Sequencing Informing Therapeutic Decisions and Personalized Approaches. AB - Multiple myeloma is a heterogeneous disease featured by different molecular subtypes. In the last decade, new therapeutics including second- and third generation proteasome inhibitors and immunomodulatory agents, monoclonal antibodies, and other novel targeted agents have completely transformed the outcome of the disease. The task ahead is to develop strategies to identify effective combinations and sequences of agents that can exploit the genetic make up of myeloma cells to improve efficacy. Moreover, a subgroup of high-risk patients who experience early disease relapse and shorter survival also requires early identification and specific intervention. Next-generation sequencing (NGS) technologies now allow us to accomplish some of these goals. As described here, besides improving our understanding of the disease, it is beginning to influence our clinical decisions and therapeutic choices. In this article, we describe the current state-of-the-art role of NGS in myeloma from identifying high-risk disease, to drug selection, and, ultimately, to guide personalized therapy. PMID- 27249753 TI - Immunotherapy: Beyond Anti-PD-1 and Anti-PD-L1 Therapies. AB - Advanced-stage non-small cell lung cancer (NSCLC) and small cell lung cancer are cancers in which chemotherapy produces a survival benefit, although it is small. We now know that anti-PD-1/PD-L1 has substantial clinical activity in both of these diseases, with an overall response rate (ORR) of 15%-20%. These responses are frequently rapid and durable, increase median overall survival (OS) compared with chemotherapy, and produce long-term survivors. Despite these very significant results, many patients do not benefit from anti-PD-1/PD-L1. This is because of the potential for malignancies to co-opt myriad immunosuppressive mechanisms other than aberrant expression of PD-L1. Conceptually, these can be divided into three categories. First, for some patients there is likely a failure to generate sufficient functional tumor antigen-specific T cells. Second, for others, tumor antigen-specific T cells may be generated but fail to enter into the tumor parenchyma. Finally, there are a large number of immunosuppressive mechanisms that have the potential to be operational within the tumor microenvironment: surface membrane immune checkpoint proteins PD-1, CTLA-4, LAG3, TIM3, BTLA, and adenosine A2AR; soluble factors and metabolic alterations interleukin (IL)-10, transforming growth factor (TGF)-beta, adenosine, IDO, and arginase; and inhibitory cells, cancer-associated fibroblasts (CAFs), regulatory T cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages. In this article, we discuss three strategies to generate more tumor reactive T cells for patients: anti-CTLA-4, therapeutic tumor vaccination, and adoptive cellular therapy, with T cells redirected to tumor antigens using T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene modification. We also review some of the various strategies in development to thwart tumor microenvironment immunosuppressive mechanisms. Strategies to drive more T cells into tumors remain a significant challenge. PMID- 27249754 TI - Local Therapy for Limited Metastatic Non-Small Cell Lung Cancer: What Are the Options and Is There a Benefit? AB - Distant metastasis is common in non-small cell lung cancer (NSCLC) and typically associated with poor prognosis. Aggressive local therapy including surgery and/or radiation for limited metastatic disease from colorectal cancer and sarcoma is associated with survival benefit and has become part of the standard of care. In this article, we review the literature and ongoing studies concerning surgery, radiation, and radiofrequency ablation for oligometastatic NSCLC. PMID- 27249755 TI - Lung Cancer Screening With Low-Dose CT: Implementation Amid Changing Public Policy at One Health Care System. AB - Screening for lung cancer with low-dose CT has evolved rapidly in recent years since the National Lung Screening Trial (NLST) results. Subsequent professional and governmental organization guidelines have shaped policy and reimbursement for the service. Increasingly available guidance describes eligible patients and components necessary for a high-quality lung cancer screening program; however, practical instruction and implementation experience is not widely reported. We launched a lung cancer screening program in the face of reimbursement and guideline uncertainties at a large academic health center. We report our experience with implementation, including challenges and proposed solutions. Initially, we saw less referrals than expected for screening, and many patients referred for screening did not clearly meet eligibility guidelines. We educated primary care providers and implemented system tools to encourage referral of eligible patients. Moreover, in response to the Centers for Medicare & Medicaid Services (CMS) final coverage determination, we report our programmatic adaptation to meet these requirements. In addition to the components common to all quality programs, individual health delivery systems will face unique barriers related to patient population, available resources, and referral patterns. PMID- 27249756 TI - Seeking New Approaches to Patients With Small Cell Lung Cancer. AB - The fundamental approach to the treatment of small cell lung cancer (SCLC) has not changed in the last several decades, with most advances being restricted to improved radiation approaches. The standard first-line chemotherapy regimen in the United States and Europe remains cisplatin or carboplatin plus etoposide in the treatment of limited stage (LS-SCLC) and extensive stage (ES-SCLC) disease. Radiation therapy is administered to those patients with LS-SCLC, whose cancer is confined to the chest in a single tolerable radiation field. This article will summarize a number of exciting observations regarding the biology of SCLC and how a deeper understanding of newly integrated targets and target pathways may lead to new and better therapeutic approaches in the near future. PMID- 27249757 TI - Treatment of Lung Cancer in Medically Compromised Patients. AB - Outcomes for patients with lung cancer have been improved substantially through the integration of surgery, radiation, and systemic therapy for patients with early-stage disease. Meanwhile, advances in our understanding of molecular mechanisms have substantially advanced our treatment of patients with advanced lung cancer through the introduction of targeted therapies, immune approaches, improvements in chemotherapy, and better supportive care. However, the majority of these advances have occurred among patients with good functional status, normal organ function, and with the social and economic support systems to be able to benefit most from these treatments. The aim of this article is to bring greater attention to management of lung cancer in patients who are medically compromised, which remains a major barrier to care delivery. Impaired performance status is associated with poor outcomes and correlates with the high prevalence of cachexia among patients with advanced lung cancer. CT imaging is emerging as a research tool to quantify muscle loss in patients with cancer, and new therapeutics are on the horizon that may provide important adjunctive therapy in the future. The benefits of cancer therapy for patients with organ failure are poorly understood because of their exclusion from clinical trials. The availability of targeted therapy and immunotherapy may provide alternatives that may be easier to deliver in this population, but clinical trials of these new agents in this population are vital. Patients with lower socioeconomic status are disproportionately affected by lung cancer because of higher rates of tobacco addiction and the impact of socioeconomic status on delay in diagnosis, treatment, and outcomes. For all patients who are medically compromised with lung cancer, multidisciplinary approaches are particularly needed to evaluate these patients and to incorporate rapidly changing therapeutics to improve outcomes. PMID- 27249758 TI - Biomarkers for Immunotherapy: Current Developments and Challenges. AB - Immunotherapy has revolutionized cancer therapy and has been named the cancer advance of the year for 2016. Checkpoint inhibitors have demonstrated unprecedented rates of durable responses in some of the most difficult-to-treat cancers; however, many treated patients do not respond, and the potential for serious side effects exists. There is a growing need to identify biomarkers that will improve the selection of patients who will best respond to therapy, further elucidate drug mechanisms of action, and help tailor therapy regimens. Biomarkers are being explored at the soluble, cellular, and genomic levels, and examples in immunotherapy include serum proteins, tumor-specific receptor expression patterns, factors in the tumor microenvironment, circulating immune and tumor cells, and host genomic factors. The search for reliable biomarkers is limited by our incomplete understanding of how immunotherapies modify the already complex immune response to cancer, as well as the contribution of immuno-editing to a dynamic and inducible tumor microenvironment and immune milieu. Furthermore, there has been little extension of any candidate assay into large, prospective studies, and the lack of standardization in measurement and interpretation restricts their validity. Both tumor-infiltrating lymphocytes and PD-L1 expression within the tumor microenvironment have been recognized as having both prognostic and predictive value for patients treated with immunotherapy. Alternately, a larger panel of gene signatures, chemokines, and other factors that correlate with response has been proposed. In this article, we will explore the status of current biomarker candidates. PMID- 27249759 TI - Less Is More: The Evolving Surgical Approach to Breast Cancer. AB - Personalized medicine is emerging as an important guiding principle in diagnosis and treatment. This means not just doing more for some, but safely doing less for others. The lessons learned about the biology of breast cancer over the last 2 decades have enabled us to understand the incredible heterogeneity of breast cancer and its associated behavior. Although much work remains, there is an emerging opportunity to identify and recognize more indolent forms of breast cancer, made more prevalent through the widespread adoption of screening. With our improving systemic therapies and improved molecular tools, we now have the opportunity to reduce the burden of treatment in women with lower-risk tumors. Our surgical treatments have evolved, with less morbid and more cosmetic procedures. In this article, we review the indications for further reducing local therapy, including adjuvant radiation. PMID- 27249760 TI - Surgical Management and Adjuvant Therapy for High-Risk and Metastatic Melanoma. AB - Wide local excision is considered routine therapy after initial diagnosis of primary melanoma to reduce local recurrences, but it does not impact survival. Sentinel node staging is recommended for melanomas of intermediate thickness, but it has also not demonstrated any indisputable therapeutic effect on survival. The prognostic value of sentinel node staging has been long established and is therefore considered routine, especially in light of the eligibility criteria for adjuvant therapy (trials). Whether completion lymph node dissection after a positive sentinel node biopsy improves survival is the question of current trials. The MSLT-2 study is best powered to show a potential benefit, but it has not yet reported any data. Another study, the German DECOG study, presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting did not show any benefit but is criticized for the underpowered design and insufficient follow up. There is no consensus on the use of adjuvant interferon in melanoma. This topic has been the focus of many studies with different regimens (low-, intermediate-, or high-dose and/or short- or long-term treatment). Adjuvant interferon has been shown to improve relapse-free survival but failed to improve overall survival. More recently, adjuvant ipilimumab has also demonstrated an improved relapse-free survival. Overall survival data have not yet been reported due to insufficient follow-up. Currently, studies are ongoing to analyze the use of adjuvant anti-PD-1 and molecular targeted therapies (vemurafenib, dabrafenib, and trametinib). In the absence of unambiguously positive approved agents, clinical trial participation remains a priority. This could change in the near future. PMID- 27249761 TI - Cancer Treatment as an Accelerated Aging Process: Assessment, Biomarkers, and Interventions. AB - An accumulating body of evidence supports the hypothesis that cancer and/or cancer treatment is associated with accelerated aging. The majority of these data come from the pediatric literature; however, a smaller yet growing body of literature points toward similar findings in the geriatric population. This is a key survivorship issue the growing number of older adults with cancer face, along with the short- and long-term impact of cancer therapy on the aging process. This article will review clinical and biologic markers of aging in older adults with cancer, use cardiovascular disease as a model of accelerated aging, and discuss potential interventions to decrease the risk. PMID- 27249762 TI - Real-World Conundrums and Biases in the Use of White Cell Growth Factors. AB - We present the 2015 American Society of Clinical Oncology (ASCO) white cell growth factors, or colony-stimulating factor (CSF), guidelines, updated from 2006. One new indication has been added-dose-intense chemotherapy for bladder cancer-to accompany the existing use for dose-dense breast cancer chemotherapy. Colony-stimulating factors remain appropriate for any regimen where the risk of febrile neutropenia is about 20% per cycle and dose reduction is not appropriate. Based on new evidence from multiple trials, CSF use is no longer indicated in treatment of lymphoma unless there are special risk factors. The United States accounts for 78% of the sales of CSF. The panel approved the use of all biosimilars, but the cost savings will be small as the price is about 80% of the branded CSFs. More biosimilars at lower cost are awaited. Methods to reduce use without harm to patients, by requiring justification according to accepted guidelines, are ongoing. PMID- 27249763 TI - Issues on the Use of White Blood Cell Growth Factors in Oncology Practice. AB - Appropriate use of myeloid growth factors may reduce the risk of neutropenic complications including febrile neutropenia (FN) in patients receiving cancer chemotherapy. The recently updated American Society of Clinical Oncology (ASCO) Guidelines on the Use of the White Blood Cell Growth Factors recommends routine prophylaxis with these agents starting in the first cycle when the risk of FN is 20% or greater. However, the risks for neutropenic complications and the risk of serious adverse consequences from FN vary considerably with different chemotherapy regimens as well as other disease-, treatment-, and patient-specific risk factors. Considerably more information is now available on the major risk factors for FN. Multivariable risk models combining factors look promising but require further validation. Most clinical studies of myeloid growth factor prophylaxis assessed relative risk (RR) of FN but were not powered to evaluate the effect of prophylaxis on disease-free or overall survival. Accumulating evidence suggests, however, that the appropriate use of these agents in selected patients may improve both short-term and long-term survival by reducing the immediate risk of mortality accompanying patients with high-risk disease developing FN as well as improving disease-free and overall survival by enabling the delivery of full dose intensity chemotherapy and reducing the risk of disease recurrence in patients treated with curative intent. Further studies to evaluate risk factors and models for FN are needed to guide clinical and shared decision making for the optimal personalized use of these agents and offer patients at increased risk the best chance of long-term disease control. PMID- 27249764 TI - Discussing the Evidence for Upstream Palliative Care in Improving Outcomes in Advanced Cancer. AB - Palliative care has received increasing attention at the American Society of Clinical Oncology (ASCO) Annual Meeting since the publication of its provisional clinical opinion on the topic in 2012. Despite frequent discussion, palliative care remains a source of some controversy and confusion in clinical practice, especially concerning who should provide it, what it encompasses, and when and how it can help patients and their families. In this article, we provide a formal definition of palliative care and review the state of the science of palliative care in oncology. Several randomized controlled trials now show that palliative care improves important outcomes for patients with cancer. Related outcome improvements include a reduction in symptoms, improved quality of life, better prognostic understanding, less depressed mood, less aggressive end-of-life care, reduced resource utilization, and even prolonged survival. As such, ASCO recommends early integration of palliative care into comprehensive cancer care for all patients with advanced disease and/or significant symptom burden. Our aim is that this summary will facilitate greater understanding about palliative care and encourage further integration of palliative care services into cancer care. More research is needed to illuminate the mechanisms of action of palliative care and to improve the specificity of palliative care applications to unique scenarios and populations in oncology. PMID- 27249765 TI - Exploiting Laboratory Insights to Improve Outcomes of Pediatric Central Nervous System Tumors. AB - Over a relatively short period of time, owing to improvements in biotechnology, our ability to identify the molecular mechanisms within pediatric brain tumors has dramatically increased. These findings have reshaped the way that we describe these diseases and have provided insights into how to better treat these often devastating diseases. Although still far from reaching the full therapeutic potential these advancements hold, the impact of these findings is steadily taking hold of pediatric brain tumor management. In this article, we summarize the major discoveries within three common pediatric brain tumor categories; medulloblastoma, ependymoma, and low-grade glioma. We discuss the current impact of these findings on treatment and the direction these findings may take the field of pediatric neuro-oncology. PMID- 27249766 TI - Neuroblastoma: A Tough Nut to Crack. AB - Neuroblastoma, an embryonal tumor arising from neural crest-derived progenitor cells, is the most common solid tumor in childhood, with more than 700 cases diagnosed per year in the United States. In the past several decades, significant advances have been made in the treatment of neuroblastoma. Treatment advances reflect improved understanding of the biology of neuroblastoma. Although amplification of MYCN was discovered in the early 1980s, our understanding of neuroblastoma oncogenesis has advanced in the last decade as a result of high throughput genomic analysis, exome and whole-genome sequencing, genome-wide association studies, and synthetic lethal drug screens. Our refined understanding of neuroblastoma biology and genetics is reflected in improved prognostic stratification and appropriate tailoring of therapy in recent clinical trials. Moreover, for high-risk neuroblastoma, a disease that was uniformly fatal 3 decades ago, recent clinical trials incorporating autologous hematopoietic transplant and immunotherapy utilizing anti-GD2 antibody plus cytokines have shown improved event-free and overall survival. These advances have resulted in a growing population of long-term survivors of neuroblastoma. Examination of the late effects and second malignant neoplasms (SMNs) in both older generations of survivors and more recently treated survivors will inform both design of future trials and surveillance guidelines for long-term follow-up. As a consequence of advances in understanding of the biology of neuroblastoma, successful clinical trials, and refined understanding of the late effects and SMNs of survivors, the promise of precision medicine is becoming a reality for patients with neuroblastoma. PMID- 27249767 TI - Manipulating the Immune System With Checkpoint Inhibitors for Patients With Metastatic Sarcoma. AB - Sarcomas are a rare group of malignant tumors of mesenchymal origin that comprise 1% of all adult cancers. Despite initial surgery, distant metastatic disease will develop in approximately 25% of patients, and standard chemotherapy has limited durable efficacy. There is a dire need for more effective and less toxic therapies for the treatment of metastatic sarcoma. The immune system plays a major role in cancer control and progression. There have been tremendous breakthroughs in other malignancies by manipulating the immune system with checkpoint inhibitors. These agents, either alone or in combination with other approaches such as radiation, chemotherapy, targeted agents, or immunotherapeutics, have generally led to improved efficacy in selected malignancies thus far. Although promising, these drugs can cause specific immune related adverse events that require prompt recognition and treatment. In addition, characterizing response and progression radiographically has become somewhat more challenging. Identifying predictive biomarkers of benefit will be essential. There remains optimism and hope that the strides made in other cancers will be emulated in sarcoma. PMID- 27249768 TI - A Value-Based Approach to Treatment of HER2-Positive Breast Cancer: Examining the Evidence. AB - Over the past decade, treatment of HER2-positive breast cancer has been revolutionized with the introduction of targeted therapies. Survival in both early and advanced HER2-positive breast cancer has improved significantly. With evidence for major clinical benefit, it is imperative that health systems evaluate new treatments to maximize the value of health expenditures. Physicians, funding agencies, and policy makers are tasked with analyzing available evidence to ensure that each individual patient receives the optimal treatment in a resource-challenged environment. PMID- 27249769 TI - Local Ablative Therapies to Metastatic Soft Tissue Sarcoma. AB - The approach to metastatic soft tissue sarcoma is complex and depends upon several factors, such as the extent of the disease, the histologic subtype of the primary tumor, the disease-free interval, patient status and comorbidities, and previous treatments. The effect of systemic chemotherapy is suboptimal, therefore local ablative therapies are often considered when the disease is limited, especially if confined to a single site/organ. Historically, surgery has been considered the treatment of choice for isolated lung metastases. This approach also has been extended to metastases in the liver, although a formal demonstration of its benefit has never been provided. Radiation therapy instead has been mainly used to obtain pain control and to reduce the risk of bone fracture and cord compression. Advances in techniques, such as the development of more precise conformational modalities and the employment of particles, may change the role of this modality in the strategic approach to metastatic soft tissue sarcoma. Recently, the use of interventional radiology in this scenario has expanded. Ablative approaches, such as radiofrequency ablation and cryoablation, have shown durable eradication of tumors. Catheter-directed therapies, such as hepatic artery embolization, are potential techniques for treating the patient who has multiple unresectable liver metastases. Understanding the timing and role of these three different modalities in the multidisciplinary approach to metastatic soft tissue sarcoma is critical to provide better care and to personalize the approach to the single patient. PMID- 27249770 TI - Interrogating the Cancer Genome to Deliver More Precise Cancer Care. AB - The aim of precision medicine is to select the best treatment option for each patient at the appropriate time in the natural history of the disease, based on understanding the molecular makeup of the tumor, with the ultimate objective of improving patient survival and quality of life. To achieve it, we must identify functionally distinct subtypes of cancers and, critically, have multiple therapy options available to match to these functional subtypes. As a result of the development of better and less costly next-generation sequencing assays, we can now interrogate the cancer genome, enabling us to use the DNA sequence itself for biomarker studies in drug development. The success of DNA-based biomarkers requires analytical validation and careful clinical qualification in prospective clinical trials. In this article, we review some of the challenges the scientific community is facing as a consequence of this sequencing revolution: reclassifying cancers based on biologic/phenotypic clusters relevant to clinical decision making; adapting how we conduct clinical trials; and adjusting our frameworks for regulatory approvals of biomarker technologies and drugs. Ultimately, we must ensure that this revolution can be safely implemented into routine clinical practice and benefit patients. PMID- 27249771 TI - Tumor Heterogeneity and Therapeutic Resistance. AB - The rapidly changing landscape of oncology has brought new light, and with it, new challenges to optimizing therapeutic strategies for patients. Although the concept of patient heterogeneity is well known to any practicing clinician, a more detailed understanding of the biologic changes that underscore the clinical picture is beginning to emerge. Thus, tumor heterogeneity has come to encompass more than just the clinical picture and can represent both intratumor and intertumor differences. Within the fields of thoracic oncology and melanoma, the discovery of key molecular drivers has resulted in landmark breakthroughs in therapy. However, the complexities of tumor genetics and the interaction within the environment continue to drive the search for better therapies. Ongoing challenges include the accurate and timely assessment of genetic changes as well as the development of resistance and the resultant compensatory mechanisms. Novel technologies, including commercially available next-generation sequencing, have allowed for a greater breadth and depth of information to be gained from a single pathologic specimen, and it is now being incorporated into routine clinical practice. Translational advances have subsequently provided valuable insight into mechanisms of resistance, with the development of novel treatment strategies. Future work will focus on novel diagnostic techniques and adaptive mechanisms that can ultimately drive the development of the next generation of cancer therapy. PMID- 27249772 TI - Emerging Therapeutic Options for HER2-Positive Breast Cancer. AB - The natural history of HER2-positive breast cancer has progressively improved since the introduction of the first anti-HER2 directed therapy (trastuzumab). Trastuzumab has significantly increased survival of patients with HER2-positive metastatic breast cancer and, after the standardization of the use of this drug in the adjuvant setting in 2005, has also avoided many disease recurrences and, consequently, saved many lives. Later on, the introduction of lapatinib offered new choices for patients with advanced HER2-positive breast cancer, although the drug has failed to show a clear efficacy in the adjuvant setting. New promising drugs have been approved to broaden the horizon of HER2-positive breast cancer such as pertuzumab or T-DM1, but we need new options to further improve the management of these diseases. In this review, we cover new strategies that are currently under evaluation for the treatment of patients with HER2-positive breast cancer, including new tyrosine kinase inhibitors (neratinib, ONT-380), new antibody-drug conjugates targeting HER2 (MM-302), and new indications of already approved drugs (T-DM1), as well as the potential dual combinations of anti-HER2 therapy with phosphoinositide 3-kinase/mTOR or cell cycle inhibitors (palbociclib, abemaciclib). Last but not least, we briefly review a new paradigm of emerging approaches that involve the host immune response, HER2 breast cancer vaccines, and other immune strategies, including immune checkpoint inhibition. PMID- 27249774 TI - Evolving Recommendations on Prostate Cancer Screening. AB - Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient. PMID- 27249773 TI - How Far Do We Go With Genetic Evaluation? Gene, Panel, and Tumor Testing. AB - The traditional model by which an individual was identified as harboring a hereditary susceptibility to cancer was to test for a mutation in a single gene or a finite number of genes associated with a particular syndrome (e.g., BRCA1 and BRCA2 for hereditary breast and ovarian cancer or mismatch repair genes for Lynch syndrome). The decision regarding which gene or genes to test for was based on a review of the patient's personal medical history and their family history. With advances in next-generation DNA sequencing technology, offering simultaneous testing for multiple genes associated with a hereditary susceptibility to cancer is now possible. These panels typically include high-penetrance genes, but they also often include moderate- and low-penetrance genes. A number of the genes included in these panels have not been fully characterized either in terms of their cancer risks or their management options. Another way some patients are unexpectedly identified as carrying a germline mutation in a cancer susceptibility gene is at the time they undergo molecular profiling of their tumor, which typically has been carried out to guide treatment choices for their cancer. This article first focuses on the issues that need to be considered when deciding between recommending more targeted testing of a single or a small number of genes associated with a particular syndrome (single/limited gene testing) versus performing a multigene panel. This article also reviews the issues regarding germline risk that occur within the setting of ordering molecular profiling of tumors. PMID- 27249775 TI - Electronic Patient-Reported Outcomes: The Time Is Ripe for Integration Into Patient Care and Clinical Research. AB - In the emerging team-based approach to delivering cancer care, collecting patient reported outcomes (PROs) provides longitudinal monitoring of treatment adverse effects, disease complications, functional statuses, and psychological states throughout the cancer continuum for all providers to use. Electronic systems offer added capabilities, including easy quantitation of individual symptom items and aggregated scales, standardization, and longitudinal tracking of patient surveys for trend analysis over time. An ideal electronic PRO (ePRO) platform is clinically relevant, validated, and reliable and would offer patient usability. Additionally, it should allow for automated responses to and from patients, have scheduling functionality, and send real-time alerts to site personnel and patients. Clinical interfaces should be easy to read and integrated into the electronic medical record. Multiple ePRO systems, often using electronic tablets, have been created and are beginning to be widely deployed. The Patient Care Monitor is one example of a system that has evolved into a comprehensive patient engagement platform, with a complete review of systems survey and capabilities for mobile health usage. Recent clinical trials have established ePRO systems as an effective method of providing information, which aids improved patient outcomes, including reduced health resource utilization and longer time on therapy. ePROs are also increasingly incorporated into clinical trials, where they can provide more thorough reporting of adverse events than can be captured by alternative methods. Mobile devices have the potential to become the method by which all members of the provider team communicate with patients both at the point-of-care and between clinic visits to optimize care delivery. PMID- 27249776 TI - Oncology Advanced Practitioners Bring Advanced Community Oncology Care. AB - Oncology care is becoming increasingly complex. The interprofessional team concept of care is necessary to meet projected oncology professional shortages, as well as to provide superior oncology care. The oncology advanced practitioner (AP) is a licensed health care professional who has completed advanced training in nursing or pharmacy or has completed training as a physician assistant. Oncology APs increase practice productivity and efficiency. Proven to be cost effective, APs may perform varied roles in an oncology practice. Integrating an AP into an oncology practice requires forethought given to the type of collaborative model desired, role expectations, scheduling, training, and mentoring. PMID- 27249777 TI - Alkyl substituted [2.2]paracyclophane-1,9-dienes. AB - [2.2]Paracyclophane-1,9-dienes substituted with n-octyl chains have been synthesised from the corresponding dithia[3.3]paracyclophanes using a benzyne induced Stevens rearrangement. The use of 2-(trimethylsilyl)phenyl trifluoromethanesulfonate and tetra-n-butylammonium fluoride as the in situ benzyne source gave significantly improved yields over traditional sources of benzyne and enabled the preparation of n-octyl substituted [2.2]paracyclophane 1,9-dienes on a multi-gram scale. PMID- 27249778 TI - Near-Infrared Phosphorescent Iridium(III) Benzonorrole Complexes Possessing Pyridine-based Axial Ligands. AB - Novel near-infrared phosphorescent iridium(III) complexes based on benzo annulated N-linked corrole analogue (termed as benzonorrole) were synthesized. The structures of the complexes revealed octahedral coordination geometries involving an organometallic iridium-carbon bond with two external axial ligands. Interestingly, the iridium(III) complex exhibits near-infrared phosphorescence at room temperature at wavelengths beyond 900 nm. The significant redshift of the emission, as compared to the corrole congener, is originated from the ligand centered triplet character. The fine-tuning of the photophysical properties of the complexes was achieved by introducing electron-donating and electron withdrawing substituents on the axial pyridine ligands. PMID- 27249779 TI - Mycobacterium tuberculosis Thioredoxin Reductase Is Essential for Thiol Redox Homeostasis but Plays a Minor Role in Antioxidant Defense. AB - Mycobacterium tuberculosis (Mtb) must cope with exogenous oxidative stress imposed by the host. Unlike other antioxidant enzymes, Mtb's thioredoxin reductase TrxB2 has been predicted to be essential not only to fight host defenses but also for in vitro growth. However, the specific physiological role of TrxB2 and its importance for Mtb pathogenesis remain undefined. Here we show that genetic inactivation of thioredoxin reductase perturbed several growth essential processes, including sulfur and DNA metabolism and rapidly killed and lysed Mtb. Death was due to cidal thiol-specific oxidizing stress and prevented by a disulfide reductant. In contrast, thioredoxin reductase deficiency did not significantly increase susceptibility to oxidative and nitrosative stress. In vivo targeting TrxB2 eradicated Mtb during both acute and chronic phases of mouse infection. Deliberately leaky knockdown mutants identified the specificity of TrxB2 inhibitors and showed that partial inactivation of TrxB2 increased Mtb's susceptibility to rifampicin. These studies reveal TrxB2 as essential thiol reducing enzyme in Mtb in vitro and during infection, establish the value of targeting TrxB2, and provide tools to accelerate the development of TrxB2 inhibitors. PMID- 27249780 TI - Defining the MO's of RGK proteins. PMID- 27249781 TI - LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality. AB - Lysergic acid diethylamide (LSD) is used recreationally and has been evaluated as an adjunct to psychotherapy to treat anxiety in patients with life-threatening illness. LSD is well-known to induce perceptual alterations, but unknown is whether LSD alters emotional processing in ways that can support psychotherapy. We investigated the acute effects of LSD on emotional processing using the Face Emotion Recognition Task (FERT) and Multifaceted Empathy Test (MET). The effects of LSD on social behavior were tested using the Social Value Orientation (SVO) test. Two similar placebo-controlled, double-blind, random-order, crossover studies were conducted using 100 MUg LSD in 24 subjects and 200 MUg LSD in 16 subjects. All of the subjects were healthy and mostly hallucinogen-naive 25- to 65-year-old volunteers (20 men, 20 women). LSD produced feelings of happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy on the MET, and impaired the recognition of sad and fearful faces on the FERT. LSD enhanced the participants' desire to be with other people and increased their prosocial behavior on the SVO test. These effects of LSD on emotion processing and sociality may be useful for LSD-assisted psychotherapy. PMID- 27249782 TI - Integrated ecosystem services assessment: Valuation of changes due to sea level rise in Galveston Bay, Texas, USA. AB - The goal of the present study was to identify the potential changes in ecosystem service values provided by wetlands in Galveston Bay, Texas, USA, under the Intergovernmental Panel on Climate Change (IPCC) A1B max (0.69 m) sea level rise scenario. Built exclusively upon the output produced during the Sea Level Affecting Marshes Model 6 (SLAMM 6) exercise for the Galveston Bay region, this study showed that fresh marsh and salt marsh present a steady decline from 2009 (initial condition) to 2100. Fresh marsh was projected to undergo the biggest changes, with the loss of approximately 21% of its extent between 2009 and 2100 under the A1B max scenario. The percentages of change for salt marsh were less prominent at approximately 12%. This trend was also shown in the values of selected ecosystem services (disturbance regulation, waste regulation, recreation, and aesthetics) provided by these habitats. An ordinary least squares regression was used to calculate the monetary value of the selected ecosystem services provided by salt marsh and fresh marsh in 2009, and in 2050 and 2100 under the A1B max scenario. The value of the selected services showed potential monetary losses in excess of US$40 million annually in 2100, compared to 2009 for fresh marsh and more than $11 million for salt marsh. The estimates provided here are only small portions of what can be lost due to the decrease in habitat extent, and they highlight the need for protecting not only built infrastructure but also natural resources from sea level rise. Integr Environ Assess Manag 2017;13:431-443. (c) 2016 SETAC. PMID- 27249783 TI - Decision Tree for Liver Resection for Hepatocellular Carcinoma. PMID- 27249784 TI - Hydrogen Storage and Selective, Reversible O2 Adsorption in a Metal-Organic Framework with Open Chromium(II) Sites. AB - A chromium(II)-based metal-organic framework Cr3 [(Cr4 Cl)3 (BTT)8 ]2 (Cr-BTT; BTT(3-) =1,3,5-benzenetristetrazolate), featuring coordinatively unsaturated, redox-active Cr(2+) cation sites, was synthesized and investigated for potential applications in H2 storage and O2 production. Low-pressure H2 adsorption and neutron powder diffraction experiments reveal moderately strong Cr-H2 interactions, in line with results from previously reported M-BTT frameworks. Notably, gas adsorption measurements also reveal excellent O2 /N2 selectivity with substantial O2 reversibility at room temperature, based on selective electron transfer to form Cr(III) superoxide moieties. Infrared spectroscopy and powder neutron diffraction experiments were used to confirm this mechanism of selective O2 binding. PMID- 27249785 TI - Hepatocyte growth factor-induced differentiation of bone mesenchymal stem cells toward hepatocyte-like cells occurs through nuclear factor-kappa B signaling in vitro. AB - Hepatocyte growth factor (HGF) is multifaceted cytokine that regulates proliferation, differentiation, morphology, and motility within numerous stem cells. More recently, HGF has been reported to induce the differentiation of bone mesenchymal stem cells (BMSCs) into mature hepatocytes, but the underlying biochemical and molecular signaling is largely unknown. We isolated BMSC from the bone marrow of rats, which were then cultured and exposed to HGF for 15 days. We subsequently assayed these cells for liver functionality and markers, and blocked NF-kB signaling at various stages of the pathway. The present results demonstrate that HGF induces the differentiation of BMSCs toward hepatocyte-like cells through the NF-kB signaling. More specifically, HGF upregulated the translocation of NF-kB to the nucleus. PMID- 27249786 TI - Inhibited early immunologic response is associated with hypertrophic scarring. AB - This study aimed to examine changes in the inflammatory response in early hypertrophic compared to normal wound healing. The immune system is thought to be involved in hypertrophic scar formation. However, the exact mechanism and time of onset of the derailment remain unknown. In a prospective observational study, skin biopsies were taken directly postwounding and 3 hours later from patients who had elective cardiothoracic surgery. The skin biopsies were analysed for mRNA, proteins and cells involved in the early inflammatory phase of wound healing. The endpoint was scar outcome (hypertrophic (HTS) or normal (NTS)) at one year after surgery. There were significant differences between the NTS and HTS groups regarding the fold changes of mRNA expression of P-selectin during surgery. Postoperative skin concentrations of inflammatory proteins IL-6, IL-8 and CCL2 were significantly lower in the HTS compared to the NTS group. Also, a trend of higher pre-operative M2 macrophage numbers was observed in the HTS group. Neutrophil numbers increased equally during surgery in both groups. The increase of P-selectin mRNA in hypertrophic wound healing could affect leucocyte migration. The decreased concentrations of inflammatory proteins in hypertrophic wound healing indicate a reduced inflammatory response, which has consequences for the treatment of hypertrophic scarring during the early inflammatory phase. In a conclusion, alterations of wound healing associated with hypertrophic scarring are visible as early as 3 hours postwounding and include a reduced rather than increased inflammatory protein response. PMID- 27249787 TI - Coy Males and Seductive Females in the Sexually Cannibalistic Colonial Spider, Cyrtophora citricola. AB - The abundance of sperm relative to eggs selects for males that maximize their number of mates and for females that choose high quality males. However, in many species, males exercise mate choice, even when they invest little in their offspring. Sexual cannibalism may promote male choosiness by limiting the number of females a male can inseminate and by biasing the sex ratio toward females because, while females can reenter the mating pool, cannibalized males cannot. These effects may be insufficient for male choosiness to evolve, however, if males face low sequential encounter rates with females. We hypothesized that sexual cannibalism should facilitate the evolution of male choosiness in group living species because a male is likely to encounter multiple receptive females simultaneously. We tested this hypothesis in a colonial orb-weaving spider, Cyrtophora citricola, with a high rate of sexual cannibalism. We tested whether mated females would mate with multiple males, and thereby shift the operational sex ratio toward females. We also investigated whether either sex chooses mates based on nutritional state and age, and whether males choose females based on reproductive state. We found that females are readily polyandrous and exhibit no mate choice related to male feeding or age. Males courted more often when the male was older and the female was younger, and males copulated more often with well-fed females. The data show that males are choosier than females for the traits we measured, supporting our hypothesis that group living and sexual cannibalism may together promote the evolution of male mate choice. PMID- 27249788 TI - Radiation exposure during the implantation of bioabsorbable vascular scaffolds versus drug-eluting stents in non-complex coronary lesions: a matched-cohort study. AB - BACKGROUND: Bioabsorbable vascular scaffolds (BVS) are a novel option for the treatment of coronary lesions in patients with stable coronary artery disease or acute coronary syndromes. We aimed to identify the influence of BVS implantation on radiation exposure and procedural outcomes compared to drug-eluting stents (DES) in daily clinical practice. METHODS: A retrospective single-center study was performed in patients undergoing percutaneous coronary intervention with BVS from 2013 to 2014. Only patients with exclusive BVS implantation (N.=78 procedures) were compared with a 2:1 matched cohort of exclusive DES-treated patients in the same period (N.=156 procedures). We used a four-step protocol to reduce radiation exposure in all procedures. Furthermore, a 12-month clinical follow-up was performed. RESULTS: Patients had similar baseline characteristics due to matching. Radiation exposure (1826 vs. 2167 cGy*cm2, P=0.673), procedure time (73 vs. 65 minutes, P=0.574), target vessel revascularization (1.3 vs. 1.3%, p=1.000 for PCI; 1.3 vs. 0.6%, P=0.616 for CABG), cardiovascular death (0.0 vs. 2.6%, P=0.304) or all-cause death (0.0 vs. 3.2%, P=0.172) were similar after implantation of BVS vs. DES. However, exposure to contrast agent (166 vs. 139 mL, P=0.028) was significantly higher in the BVS group. CONCLUSIONS: The implantation of BVS in combination with a simple four-step protocol is a feasible option for interventional treatment of non-complex coronary lesions without significant impact on radiation exposure or outcome measures in daily clinical routine. PMID- 27249789 TI - Effect of intracoronary nitroprusside injection on flow recovery during primary PCI in acute STEMI patients. AB - BACKGROUND: The no/slow reflow phenomenon during primary percutaneous coronary intervention (PPCI) causes the destruction of the coronary microcirculation and further myocardial damage. Some studies have shown that intracoronary nitroprusside infusion is a safe and effective method for managing the no/slow reflow phenomenon. However, it is uncertain whether the injection of nitroprusside at a specific time point during PPCI can most effectively prevent no-reflow. In this study, we investigated the effect of the timing of an intracoronary nitroprusside injection on flow recovery during PPCI in patients with ST elevation acute myocardial infarction (STEMI). METHODS: One hundred twenty consecutive patients with STEMI who underwent PPCI were enrolled in the study. Patients who fulfilled the eligibility criteria were randomly allocated to three groups: control group (N.=40) received no nitroprusside before they completed PCI; the second group (N.=40) received nitroprusside before balloon dilatation; and the third group (N.=40) received nitroprusside after each balloon dilatation and before contrast agent refilling. The baseline clinical variables and the details of the PCI procedure were collected. The thrombolysis in myocardial infarction (TIMI) flow grades and the corrected TIMI frame count (cTFC) were evaluated immediately after stent implantation was completed. RESULTS: There were no significant differences in the baseline characteristics, antithrombotic drugs given before PCI, and details of the PCI procedure among the three groups (P>0.05). The incidence of TIMI grade 3 after PCI was significantly higher in the nitroprusside group than in the control group (P=0.025), whereas cTFC was significantly lower in the nitroprusside group (26.6+/-15.2) than in the control group (38.1+/-21.3, P=0.001). The incidence of TIMI grade 3 after PCI was significantly higher in the third group than in the second group (P=0.045), and cTFC was significantly lower in the third group (21.5+/-9.5) than in the second group (31.2+/-18.3, P=0.002). Multivariable linear regression analyses showed that the intracoronary nitroprusside injection time was a significant predictor of cTFC after PCI. CONCLUSIONS: These data suggest that the intracoronary injection of nitroprusside significantly reduced the incidence of no/slow reflow during PPCI. The intracoronary injection of nitroprusside most effectively prevented the no/slow reflow phenomenon when administered between balloon dilatation and contrast agent refilling during PPCI. PMID- 27249790 TI - Radiological anatomy of upper limb arteries and their anatomical variability: implications for endovascular treatment in critical hand ischemia. AB - Critical hand ischemia (CHI) is a quite uncommon but highly disabling condition, generally caused by chronic occlusive arterial disease. For a correct approach to the endovascular treatment of these patients, good knowledge of the normal vascular anatomy and of the most frequently encountered vascular anatomical variations is of paramount importance. In the present paper a description of the normal vascular anatomy of the upper limb and of the most commonly encountered anatomical variations is provided, focusing on the implications for endovascular treatment of patients with CHI. Moreover, data of 151 patients with 172 critically ischemic hands treated at our institution between 2004 and 2016 are presented. PMID- 27249791 TI - Structured self-monitoring of blood glucose regimens improve glycemic control in poorly controlled Chinese patients on insulin therapy: Results from COMPASS. AB - BACKGROUND: The use of self-monitoring of blood glucose (SMBG) among patients with insulin-treated, type 2 diabetes (T2DM) in China is suboptimal. Herein we evaluated the effectiveness of structured SMBG for improving glycemic control and increasing the frequency of SMBG. METHODS: Insulin-treated (>3 months) T2DM patients aged >=18 years with HbA1c >8.0 % (64 mmol/mol) were recruited to the study. They received SMBG materials and were advised on a structured SMBG regimen for their insulin therapy. Patients were trained to self-adjust insulin dosage according to SMBG readings and were seen by physicians at Months 3 and 6. Endpoints included changes in HbA1c, SMBG frequency, and hypoglycemia frequency. RESULTS: The study enrolled 820 patients, with mean (+/- SD) age 55.1 +/- 9.8 years, body mass index 24.9 +/- 3.6 kg/m2 , HbA1c 9.7 +/- 1.6 % (83 mmol/mol), and diabetes duration 9.8 +/- 7.1 years, with median insulin therapy of 30.3 (3.0 274.1) months, from 19 Chinese clinics. By Month 3, 99.9 % of patients performed daily SMBG. At Months 3 and 6, HbA1c had decreased from baseline (-1.81 % and 1.73 %, respective; P < 0.0001 for both), with reduced hypoglycemia. In addition, 36.2 % and 39.9 % of patients achieved HbA1c <7.0 % (53 mmol/mol) at Months 3 and 6, respectively. The largest HbA1c improvements were for patients with a shorter duration of diabetes and insulin therapy. CONCLUSIONS: A structured SMBG regimen, with training on interpretation of and responses to SMBG readings, increased SMBG frequency and improved HbA1c and the management of insulin-treated T2DM. PMID- 27249792 TI - The Role of Trap-assisted Recombination in Luminescent Properties of Organometal Halide CH3NH3PbBr3 Perovskite Films and Quantum Dots. AB - Hybrid metal halide perovskites have been paid enormous attentions in photophysics research, whose excellent performances were attributed to their intriguing charge carriers proprieties. However, it still remains far from satisfaction in the comprehensive understanding of perovskite charge-transport properities, especially about trap-assisted recombination process. In this Letter, through time-resolved transient absorption (TA) and photoluminescence (PL) measurements, we provided a relative comprehensive investigation on the charge carriers recombination dynamics of CH3NH3PbBr3 (MAPbBr3) perovskite films and quantum dots (QDs), especially about trap-assisted recombination. It was found that the integral recombination mode of MAPbBr3 films was highly sensitive to the density distribution of generated charge carriers and trap states. Additional, Trap effects would be gradually weakened with elevated carrier densities. Furthermore, the trap-assisted recombination can be removed from MAPbBr3 QDs through its own surface passivation mechanism and this specialty may render the QDs as a new material in illuminating research. This work provides deeper physical insights into the dynamics processes of MAPbBr3 materials and paves a way toward more light-harvesting applications in future. PMID- 27249793 TI - Potential for Local Fertilization: A Benthocosm Test of Long-Term and Short-Term Effects of Mussel Excretion on the Plankton. AB - Mussel aquaculture has expanded worldwide and it is important to assess its impact on the water column and the planktonic food web to determine the sustainability of farming practices. Mussel farming may affect the planktonic food web indirectly by excreting bioavailable nutrients in the water column (a short-term effect) or by increasing nutrient effluxes from biodeposit-enriched sediments (a long-term effect). We tested both of these indirect effects in a lagoon by using plankton-enclosing benthocosms that were placed on the bottom of a shallow lagoon either inside of a mussel farm or at reference sites with no history of aquaculture. At each site, half of the benthocosms were enriched with seawater that had held mussels (excretion treatment), the other half received non enriched seawater as a control treatment. We monitored nutrients ([PO43-] and [NH4+]), dissolved oxygen and plankton components (bacteria, the phytoplankton and the zooplankton) over 5 days. We found a significant relationship between long-term accumulation of mussel biodeposits in sediments, water-column nutrient concentrations and plankton growth. Effects of mussel excretion were not detected, too weak to be significant given the spatial and temporal variability observed in the lagoon. Effects of mussels on the water column are thus likely to be coupled to benthic processes in such semi-enclosed water bodies. PMID- 27249794 TI - Expression of PAX8 Target Genes in Papillary Thyroid Carcinoma. AB - PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis. PMID- 27249795 TI - Corticosterone regulates fear memory via Rac1 activity in the hippocampus. AB - Stressful events can generate enduring memories, which may induce certain psychiatric disorders such as post-traumatic stress disorder (PTSD). However, the underlying molecular mechanisms in these processes remain unclear. In this study, we examined whether the active form of the small G protein Rac1, Rac1-GTP, is involved in fear memory. Firstly, we detected the time course changes of Rac1-GTP after foot shocks (a strong stressor) and exogenous corticosterone (CORT) treatment. The data showed that stress and CORT induced the downregulation of Rac1-GTP in the hippocampus. Changes in the serum CORT level were negatively correlated with the level of Rac1-GTP. Additionally, a glucocorticoid receptor antagonist, RU38486, not only recovered the expression of Rac1-GTP but also impaired fear memory. Furthermore, systemic administration of NSC23766, an inhibitor of Rac1-GTP, improved fear memory at 1.5 and 24h. Therefore, Rac1 activity plays a critical role in stress-related cognition and may be a potential target in stress-related disorders. PMID- 27249796 TI - Correction: Galactomannan Testing and the Incidence of Invasive Pulmonary Aspergillosis: A 10-Year Nationwide Population-Based Study in Taiwan. AB - [This corrects the article DOI: 10.1371/journal.pone.0149964.]. PMID- 27249797 TI - Effects of Red Blood Cell Transfusions on the Risk of Developing Complications or Death: An Observational Study of a Cohort of Very Low Birth Weight Infants. AB - Background The aim of this study was to evaluate the association between red blood cell (RBC) transfusions on the risk of death, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) in very low birth weight (VLBW) infants. Study Design and Methods This is an observational study. Data were entered prospectively into the study database at the time of the first transfusion. Clinical characteristics, adverse events, and outcomes of the patients transfused in the first 28 days of life were compared with the population of VLBW infants not transfused during the same period. The association among birth weight, gestational age, comorbidities, and the number of transfusions was estimated with a Poisson regression model. The association between the composite outcome and the occurrence of death, ROP, or BPD separately considered and a set of covariates was estimated with a logistic regression model. Results We enrolled 641 VLBW infants, 42% of whom were transfused. Transfusions were associated with the risk of developing the composite outcome, independently from other conditions; this risk correlated with several transfusions >= 3 (odds ratio: 5.88, 95% confidence interval: 2.74-12.6). ROP and BPD were associated with several transfusions >= 3. Conclusion We observed an association between RBC transfusions and the composite risk of death or ROP, BPD, and NEC. PMID- 27249798 TI - The role of the glucose-sensing transcription factor carbohydrate-responsive element-binding protein pathway in termite queen fertility. AB - Termites are among the few animals that themselves can digest the most abundant organic polymer, cellulose, into glucose. In mice and Drosophila, glucose can activate genes via the transcription factor carbohydrate-responsive element binding protein (ChREBP) to induce glucose utilization and de novo lipogenesis. Here, we identify a termite orthologue of ChREBP and its downstream lipogenic targets, including acetyl-CoA carboxylase and fatty acid synthase. We show that all of these genes, including ChREBP, are upregulated in mature queens compared with kings, sterile workers and soldiers in eight different termite species. ChREBP is expressed in several tissues, including ovaries and fat bodies, and increases in expression in totipotent workers during their differentiation into neotenic mature queens. We further show that ChREBP is regulated by a carbohydrate diet in termite queens. Suppression of the lipogenic pathway by a pharmacological agent in queens elicits the same behavioural alterations in sterile workers as observed in queenless colonies, supporting that the ChREBP pathway partakes in the biosynthesis of semiochemicals that convey the signal of the presence of a fertile queen. Our results highlight ChREBP as a likely key factor for the regulation and signalling of queen fertility. PMID- 27249802 TI - Internal modeling of upcoming speech: A causal role of the right posterior cerebellum in non-motor aspects of language production. AB - Some language processing theories propose that, just as for other somatic actions, self-monitoring of language production is achieved through internal modeling. The cerebellum is the proposed center of such internal modeling in motor control, and the right cerebellum has been linked to an increasing number of language functions, including predictive processing during comprehension. Relating these findings, we tested whether the right posterior cerebellum has a causal role for self-monitoring of speech errors. Participants received 1 Hz repetitive transcranial magnetic stimulation during 15 min to lobules Crus I and II in the right hemisphere, and, in counterbalanced orders, to the contralateral area in the left cerebellar hemisphere (control) in order to induce a temporary inactivation of one of these zones. Immediately afterwards, they engaged in a speech production task priming the production of speech errors. Language production was impaired after right compared to left hemisphere stimulation, a finding that provides evidence for a causal role of the cerebellum during language production. We interpreted this role in terms of internal modeling of upcoming speech through a verbal working memory process used to prevent errors. PMID- 27249799 TI - NADPH oxidases as electrochemical generators to produce ion fluxes and turgor in fungi, plants and humans. AB - The NOXs are a family of flavocytochromes whose basic structure has been largely conserved from algae to man. This is a very simple system. NADPH is generally available, in plants it is a direct product of photosynthesis, and oxygen is a largely ubiquitous electron acceptor, and the electron-transporting core of an FAD and two haems is the minimal required to pass electrons across the plasma membrane. These NOXs have been shown to be essential for diverse functions throughout the biological world and, lacking a clear mechanism of action, their effects have generally been attributed to free radical reactions. Investigation into the function of neutrophil leucocytes has demonstrated that electron transport through the prototype NOX2 is accompanied by the generation of a charge across the membrane that provides the driving force propelling protons and other ions across the plasma membrane. The contention is that the primary function of the NOXs is to supply the driving force to transport ions, the nature of which will depend upon the composition and characteristics of the local ion channels, to undertake a host of diverse functions. These include the generation of turgor in fungi and plants for the growth of filaments and invasion by appressoria in the former, and extension of pollen tubes and root hairs, and stomatal closure, in the latter. In neutrophils, they elevate the pH in the phagocytic vacuole coupled to other ion fluxes. In endothelial cells of blood vessels, they could alter luminal volume to regulate blood pressure and tissue perfusion. PMID- 27249803 TI - Profile of Class I Histone Deacetylases (HDAC) by Human Dendritic Cells after Alcohol Consumption and In Vitro Alcohol Treatment and Their Implication in Oxidative Stress: Role of HDAC Inhibitors Trichostatin A and Mocetinostat. AB - Epigenetic mechanisms have been shown to play a role in alcohol use disorders (AUDs) and may prove to be valuable therapeutic targets. However, the involvement of histone deacetylases (HDACs) on alcohol-induced oxidative stress of human primary monocyte-derived dendritic cells (MDDCs) has not been elucidated. In the current study, we took a novel approach combining ex vivo, in vitro and in silico analyses to elucidate the mechanisms of alcohol-induced oxidative stress and role of HDACs in the periphery. ex vivo and in vitro analyses of alcohol-modulation of class I HDACs and activity by MDDCs from self-reported alcohol users and non alcohol users was performed. Additionally, MDDCs treated with alcohol were assessed using qRT-PCR, western blot, and fluorometric assay. The functional effects of alcohol-induce oxidative stress were measured in vitro using PCR array and in silico using gene expression network analysis. Our findings show, for the first time, that MDDCs from self-reported alcohol users have higher levels of class I HDACs compare to controls and alcohol treatment in vitro differentially modulates HDACs expression. Further, HDAC inhibitors (HDACi) blocked alcohol induction of class I HDACs and modulated alcohol-induced oxidative stress related genes expressed by MDDCs. In silico analysis revealed new target genes and pathways on the mode of action of alcohol and HDACi. Findings elucidating the ability of alcohol to modulate class I HDACs may be useful for the treatment of alcohol-induced oxidative damage and may delineate new potential immune modulatory mechanisms. PMID- 27249804 TI - The within-person association between alcohol use and sleep duration and quality in situ: An experience sampling study. AB - OBJECTIVE: Despite evidence for detrimental effects of alcohol on sleep quality in laboratory studies, alcohol is commonly used as a self-prescribed sleep aid. This study examined the within-person associations of alcohol use with sleep duration and quality in everyday life to gain insight into the ecological validity of laboratory findings on the association between sleep and alcohol. METHOD: A sample of 150 adults (age 19-89years) were followed for 60+days as part of an intensive experience sampling study wherein participants provided daily reports of their alcohol use, sleep duration, and sleep quality. Within-person and between-person associations of daily sleep duration and quality with alcohol use were examined using multilevel models. RESULTS: A significant, negative within-person association was observed between sleep quality and alcohol use. Sleep quality was lower on nights following alcohol use. Sleep duration did not vary as a function of within-person variation in alcohol use. CONCLUSIONS: In line with laboratory assessments, alcohol use was associated with low sleep quality but was not associated with sleep duration, suggesting that laboratory findings generalize to everyday life. This examination of individuals' daily lives suggests that alcohol does not systematically improve sleep quality or duration in real life. PMID- 27249805 TI - Problematic Internet use, well-being, self-esteem and self-control: Data from a high-school survey in China. AB - Given the prevalence of Internet use among youth, there is concern that a subset of Internet-using youth may exhibit problematic or addictive patterns of Internet use. The present study examines the association between problematic Internet use (PIU), demographic variables, and health-related measures among Chinese adolescents. Survey data from 1552 adolescents (male=653, mean age=15.43years) from Jilin Province, China, were collected. According to the Young Diagnostic Questionnaire for Internet Addiction (YDQ), 77.8% (n=1207), 16.8% (n=260), and 5.5% (n=85) showed adaptive, maladaptive, and problematic Internet use, respectively. Multinomial logistic regression analysis revealed that gender and family income per month differed between youth showing problematic and adaptive patterns of Internet use. Well-being, self-esteem, and self-control were related to severity of problematic Internet use, with greater severity typically associated with poorer measures in each domain. The findings that severity of problematic Internet use is associated with specific socio-demographic features and temperamental and well-being measures suggest that specific groups of youth may be particularly vulnerable to developing problematic Internet use. Early prevention/intervention programs targeting at-risk groups may help improve public health. PMID- 27249806 TI - Minority stress is longitudinally associated with alcohol-related problems among sexual minority women. AB - Compared to sexual minority men and heterosexual women, sexual minority women report elevated alcohol use in young adulthood. Heavy alcohol use and alcohol use disorders disproportionately affect sexual minority women across the lifespan, yet there is limited research investigating reasons for such associations. The present study investigates longitudinal associations between minority stress and both alcohol use as well as self-rated drinking consequences. Participants (N=1057) were self-identified lesbian (40.5%) and bisexual (59.5%) women between the ages of 18 to 25 recruited from across the U.S. using online advertisements. Participants completed four annual surveys. Hurdle mixed effects models were used to assess associations between minority stress and typical weekly drinking and drinking consequences one year later. Minority stress was not significantly associated with subsequent typical drinking. However, minority stress was significantly associated with having any alcohol consequences as well as the count of alcohol consequences one year later after controlling for covariates. Consistent with extant literature, this study provides evidence for a prospective association between minority stress experienced by sexual minority women and drinking consequences. This study also provides support for the potential impact of efforts to reduce minority stress faced by sexual minority women. PMID- 27249808 TI - Transoesophageal echocardiography before DC cardioversion: a survey of clinical practice in the UK. AB - Transoesophageal echocardiography (TOE) can be used to expedite DC cardioversion (DCCV) in the absence of adequate anticoagulation. There are no guidelines for the management of sedation or general anaesthetic. We performed a survey of NHS echocardiography departments to determine UK practice. Responses were received from 95 (50%) of 189 centres, and TOE-guided DCCV was performed in 81 centres. The numbers were <10 a year in 41 (50%), 10 - 50 in 31 (38%), 50 - 100 in 8 (10%) and >100 in 4 (5%) centres. Sedation for TOE was a usual practice in 67 (80%) centres but often temporally disconnected from DCCV due to logistical reasons. TOE under general anaesthetic was performed in 35 (43%) centres and as the usual method in 16 (20%). The patient was in the supine position with endotracheal intubation in 20 (57%) of centres, but without any form of airway protection while supine in 5 (14%). There is variability in practice across centres in the UK, in part due to limitations to services in most centres but also because of an absence of UK guidelines. The development of national standards may address this and aid in the development of local business cases to extend services. PMID- 27249807 TI - Ethical considerations and potential threats to validity for three methods commonly used to collect geographic information in studies among people who use drugs. AB - BACKGROUND: Analyses with geographic data can be used to identify "hot spots" and "health service deserts", examine associations between proximity to services and their use, and link contextual factors with individual-level data to better understand how environmental factors influence behaviors. Technological advancements in methods for collecting this information can improve the accuracy of contextually-relevant information; however, they have outpaced the development of ethical standards and guidance, particularly for research involving populations engaging in illicit/stigmatized behaviors. Thematic analysis identified ethical considerations for collecting geographic data using different methods and the extent to which these concerns could influence study compliance and data validity. METHODS: In-depth interviews with 15 Baltimore residents (6 recruited via flyers and 9 via peer-referral) reporting recent drug use explored comfort with and ethics of three methods for collecting geographic information: (1) surveys collecting self-reported addresses/cross-streets, (2) surveys using web-based maps to find/confirm locations, and (3) geographical momentary assessments (GMA), which collect spatiotemporally referenced behavioral data. RESULTS: Survey methods for collecting geographic data (i.e., addresses/cross streets and web-based maps) were generally acceptable; however, participants raised confidentiality concerns regarding exact addresses for illicit/stigmatized behaviors. Concerns specific to GMA included burden of carrying/safeguarding phones and responding to survey prompts, confidentiality, discomfort with being tracked, and noncompliance with study procedures. Overall, many felt that confidentiality concerns could influence the accuracy of location information collected for sensitive behaviors and study compliance. CONCLUSIONS: Concerns raised by participants could result in differential study participation and/or study compliance and questionable accuracy/validity of location data for sensitive behaviors. PMID- 27249809 TI - Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population. AB - PURPOSE: Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. METHODS: This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. RESULTS: All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (beta-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (beta-coef: -0.20 & -0.12, both P < 0.05) after adjusting for clinical variables. CONCLUSION: Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population. PMID- 27249810 TI - Prognostic utility of blood pressure-adjusted global and basal systolic longitudinal strain. AB - Assessment of global longitudinal systolic strain (GLS) and longitudinal systolic strain of the basal segments (BLS) has shown prognostic value in cardiac disorders. However, strain is reduced with increased afterload. We assessed the prognostic value of GLS and BLS adjusted for afterload. GLS and BLS were determined in 272 subjects with normal ejection fraction and no known coronary disease, or significant valve disease. Systolic blood pressure (SP) and diastolic blood pressure (DP) obtained at the time of echocardiography were used to adjust GLS and BLS as follows: strain*SP (mmHg)/120 mmHg and strain*DP (mmHg)/80 mmHg. Patients were followed for cardiac events and mortality. The mean age was 53+/-15 years and 53% had hypertension. There were 19 cardiac events and 70 deaths over a mean follow-up of 26+/-14 months. Cox analysis showed that left ventricular mass index (P=0.001), BLS (P<0.001), and DP-adjusted BLS (P<0.001) were independent predictors of cardiac events. DP-adjusted BLS added incremental value (P<0.001) to the other two predictors and had an area under the curve of 0.838 for events. DP (P=0.001), age (P=0.001), ACE inhibitor use (P=0.017), and SP-adjusted BLS (P=0.012) were independent predictors of mortality. SP-adjusted BLS added incremental value (P=0.014) to the other independent predictors. In conclusion, DP-adjusted BLS and SP-adjusted BLS were independent predictors of cardiac events and mortality, respectively. Blood pressure-adjusted strain added incremental prognostic value to other predictors of outcome. PMID- 27249811 TI - A comparison of two forms of the continuity equation in the Trifecta bovine pericardial aortic valve. AB - AIM: To compare the classical and simplified form of the continuity equation in small Trifecta valves. METHODS: This is a retrospective analysis of post operative echocardiograms performed for clinical reasons after implantation of Trifecta bioprosthetic valves. RESULTS: There were 60 patients aged 74 (range 38 89) years. For the valves of size 19, 21 and 23mm, the mean gradient was 11.3, 10.7 and 9.7mmHg, respectively. The effective orifice areas by the classical form of the continuity equation were 1.4, 1.7 and 1.9cm(2), respectively. There was a good correlation between the two forms of the continuity equation, but they were significantly different using a t-test (P<0.00001). Results using the classical form were a mean 0.11 (s.d. 0.18)cm(2) larger than those using the simple formula. CONCLUSION: Haemodynamic function of the Trifecta valve in the small aortic root is good. There are significant differences between the classical and simplified forms of the continuity equation. PMID- 27249812 TI - Sudden cardiac arrest and coexisting mitral valve prolapse: a case report and literature review. AB - The aetiology of sudden cardiac arrest can often be identified to underlying cardiac pathology. Mitral valve prolapse is a relatively common valvular pathology with symptoms manifesting with increasing severity of mitral regurgitation (MR). It is unusual for severe MR to be present without symptoms, and there is growing evidence that this subset of patients may be at increased risk of sudden cardiac arrest or death. The difficulty lies in identifying those patients at risk and applying measures that are appropriate to halting progression to cardiac arrest. This article examines the association of mitral valve prolapse with cardiac arrests, the underlying pathophysiological process and the strategies for identifying those at risk. PMID- 27249813 TI - An extracardiac unruptured right sinus of valsalva aneurysm complicated with atherothrombosis. AB - SummaryWe present quite a rare case of extracardiac unruptured right sinus of valsalva aneurysm (SVA) complicated with atherothrombosis in a young adult man. A 35-year-old male with a giant unruptured SVA arising from the right coronary sinus (RCS) with extracardiac protrusion was diagnosed by echocardiography. Contrast-enhanced computed tomography (CT) revealed a huge calcified aneurysm with mural thrombi originating from the aortic root, and about 80% stenosis at the initial segment of the right coronary artery (RCA). Intraoperative exploration demonstrated a giant unruptured aneurysm arising from the RCS. Different from other SVAs reported before, this aneurismal wall appeared thick and atheromatous-like. In this aneurysm, there was a small localized intima tearing and mural thrombosis, and the orifice of the RCA was almost blocked. This patient underwent surgical patch repair to prevent aneurysm rupture and coronary artery bypass grafting for RCA revascularization. In conclusion, the pathological examination demonstrated marked foam cells, inflammatory cells, and thrombosis in the aneurismal wall. LEARNING POINTS: Echocardiographic characteristics of sinus of valsalva aneurysm (SVA).Diagnostic evaluation of extracardiac unruptured SVA.Pathology of rare SVA. PMID- 27249814 TI - Acute myocarditis with normal wall motion detected with 2D speckle tracking echocardiography. AB - SummaryWe present the case of a 26-year-old male with acute tonsillitis who was referred for coronary angiography because of chest pain, elevated cardiac biomarkers, and biphasic T waves. The patient had no cardiovascular risk factors. Echocardiography showed no wall motion abnormalities and no pericardial effusion. 2D speckle tracking revealed distinct decreased regional peak longitudinal systolic strain in the lateral and posterior walls. Ischemic disease was extremely unlikely in view of his young age, negative family history regarding coronary artery disease, and lack of regional wall motion abnormalities on the conventional 2D echocardiogram. Coronary angiography was deferred as myocarditis was suspected. To confirm the diagnosis, cardiac magnetic resonance tomography (MRT) was performed, showing subepicardial delayed hyperenhancement in the lateral and posterior walls correlating closely with the strain pattern obtained by 2D speckle tracking echocardiography. With a working diagnosis of acute myocarditis associated with acute tonsillitis, we prescribed antibiotics and nonsteroidal anti-inflammatory drugs. The patient's clinical signs resolved along with normalization of serum creatine kinase (CK) levels, and the patient was discharged on the third day after admission. LEARNING POINTS: Acute myocarditis can mimic acute coronary syndromes.Conventional 2D echocardiography lacks specific features for detection of subtle regional wall motion abnormalities.2D speckle tracking expands the scope of echocardiography in identifying myocardial dysfunction derived from edema in acute myocarditis. PMID- 27249815 TI - Anterior mitral valve aneurysm: a rare sequelae of aortic valve endocarditis. AB - SummaryIn intravenous drug abusers, infective endocarditis usually involves right sided valves, with Staphylococcus aureus being the most common etiologic agent. We present a patient who is an intravenous drug abuser with left-sided (aortic valve) endocarditis caused by Enterococcus faecalis who subsequently developed an anterior mitral valve aneurysm, which is an exceedingly rare complication. A systematic literature search was conducted which identified only five reported cases in the literature of mitral valve aneurysmal rupture in the setting of E. faecalis endocarditis. Real-time 3D-transesophageal echocardiography was critical in making an accurate diagnosis leading to timely intervention. LEARNING OBJECTIVES: Early recognition of a mitral valve aneurysm (MVA) is important because it may rupture and produce catastrophic mitral regurgitation (MR) in an already seriously ill patient requiring emergency surgery, or it may be overlooked at the time of aortic valve replacement (AVR).Real-time 3D transesophageal echocardiography (RT-3DTEE) is much more advanced and accurate than transthoracic echocardiography for the diagnosis and management of MVA. PMID- 27249816 TI - Clinical utility of speckle-tracking echocardiography in cardiac resynchronisation therapy. AB - Cardiac resynchronisation therapy (CRT) can profoundly improve outcome in selected patients with heart failure; however, response is difficult to predict and can be absent in up to one in three patients. There has been a substantial amount of interest in the echocardiographic assessment of left ventricular dyssynchrony, with the ultimate aim of reliably identifying patients who will respond to CRT. The measurement of myocardial deformation (strain) has conventionally been assessed using tissue Doppler imaging (TDI), which is limited by its angle dependence and ability to measure in a single plane. Two-dimensional speckle-tracking echocardiography is a technique that provides measurements of strain in three planes, by tracking patterns of ultrasound interference ('speckles') in the myocardial wall throughout the cardiac cycle. Since its initial use over 15 years ago, it has emerged as a tool that provides more robust, reproducible and sensitive markers of dyssynchrony than TDI. This article reviews the use of two-dimensional and three-dimensional speckle-tracking echocardiography in the assessment of dyssynchrony, including the identification of echocardiographic parameters that may hold predictive potential for the response to CRT. It also reviews the application of these techniques in guiding optimal LV lead placement pre-implant, with promising results in clinical improvement post-CRT. PMID- 27249817 TI - Modulation of natural killer cell functions by interactions between 2B4 and CD48 in cis and in trans. AB - SLAM-related receptors (SRRs) are important modulators of immune cell function. While most SRRs are homophilic, 2B4 (CD244) interacts with CD48, a GPI-anchored protein expressed on many haematopoietic cells. Here we show that natural killer (NK) cell-expressed 2B4 not only binds in trans to CD48 on neighbouring cells but also interacts in cis with CD48 on the same cell. 2B4 uses the same binding site to interact with CD48 in cis and in trans and structural flexibility of 2B4 is necessary for the cis interaction. Furthermore, the cis interaction is sufficient to induce basal phosphorylation of 2B4. However, cis interaction reduces the ability of 2B4 to bind CD48 in trans As a consequence, stimulation-dependent phosphorylation of 2B4 upon binding to CD48 positive target cells is reduced. Interfering with the cis interaction therefore enhanced the lysis of CD48 expressing tumour cells. These data show that the density of 2B4 and CD48 on both the NK cell and the potential target cell modulates NK cell activity. PMID- 27249818 TI - In vivo myosin step-size from zebrafish skeletal muscle. AB - Muscle myosins transduce ATP free energy into actin displacement to power contraction. In vivo, myosin side chains are modified post-translationally under native conditions, potentially impacting function. Single myosin detection provides the 'bottom-up' myosin characterization probing basic mechanisms without ambiguities inherent to ensemble observation. Macroscopic muscle physiological experimentation provides the definitive 'top-down' phenotype characterizations that are the concerns in translational medicine. In vivo single myosin detection in muscle from zebrafish embryo models for human muscle fulfils ambitions for both bottom-up and top-down experimentation. A photoactivatable green fluorescent protein (GFP)-tagged myosin light chain expressed in transgenic zebrafish skeletal muscle specifically modifies the myosin lever-arm. Strychnine induces the simultaneous contraction of the bilateral tail muscles in a live embryo, causing them to be isometric while active. Highly inclined thin illumination excites the GFP tag of single lever-arms and its super-resolution orientation is measured from an active isometric muscle over a time sequence covering many transduction cycles. Consecutive frame lever-arm angular displacement converts to step-size by its product with the estimated lever-arm length. About 17% of the active myosin steps that fall between 2 and 7 nm are implicated as powerstrokes because they are beyond displacements detected from either relaxed or ATP depleted (rigor) muscle. PMID- 27249820 TI - Maximal Lactate Steady State's Dependence on Cycling Cadence. AB - The maximal lactate steady state (MLSS) depicts the highest blood lactate concentration (BLC) that can be maintained over time without a continual accumulation at constant prolonged workload. In cycling, no difference in the MLSS was combined with lower power output related to peak workload (IMLSS) at 100 than at 50 rpm. MLSS coincides with a respiratory exchange ratio (RER) close to 1. Recently, at incremental exercise, an RER of 1 was found at similar workload and similar intensity but higher BLC at 100 than at 50 rpm. Therefore, the authors reassessed a potential effect of cycling cadences on the MLSS and tested the hypothesis that the MLSS would be higher at 105 than at 60 rpm with no difference in IMLSS in a between-subjects design (n = 16, age 25.1 +/- 1.9 y, height 178.4 +/- 6.5 cm, body mass 70.3 +/- 6.5 kg vs n = 16, 23.6 +/- 3.0 y, 181.4 +/- 5.6 cm, 72.5 +/- 6.2 kg; study I) and confirmed these findings in a within-subject design (n = 12, 25.3 +/- 2.1 y, 175.9 +/- 7.7 cm, 67.8 +/- 8.9 kg; study II). In study I, the MLSS was lower at 60 than at 105 rpm (4.3 +/- 0.7 vs 5.4 +/- 1.0 mmol/L; P = .003) with no difference in IMLSS (68.7% +/- 5.3% vs 71.8% +/- 5.9%). Study II confirmed these findings on MLSS (3.4 +/- 0.8 vs 4.5 +/ 1.0 mmol/L; P = .001) and IMLSS (65.0% +/- 6.8% vs 63.5% +/- 6.3%; P = .421). The higher MLSS at 105 than at 60 rpm combined with an invariance of IMLSS and RER close to 1 at MLSS supports the hypothesis that higher cadences can induce a preservation of carbohydrates at given BLC levels during low-intensity, high volume training sessions. PMID- 27249819 TI - Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform. AB - Abundant evidence for translation within the 5' leaders of many human genes is rapidly emerging, especially, because of the advent of ribosome profiling. In most cases, it is believed that the act of translation rather than the encoded peptide is important. However, the wealth of available sequencing data in recent years allows phylogenetic detection of sequences within 5' leaders that have emerged under coding constraint and therefore allow for the prediction of functional 5' leader translation. Using this approach, we previously predicted a CUG-initiated, 173 amino acid N-terminal extension to the human tumour suppressor PTEN. Here, a systematic experimental analysis of translation events in the PTEN 5' leader identifies at least two additional non-AUG-initiated PTEN proteoforms that are expressed in most human cell lines tested. The most abundant extended PTEN proteoform initiates at a conserved AUU codon and extends the canonical AUG initiated PTEN by 146 amino acids. All N-terminally extended PTEN proteoforms tested retain the ability to downregulate the PI3K pathway. We also provide evidence for the translation of two conserved AUG-initiated upstream open reading frames within the PTEN 5' leader that control the ratio of PTEN proteoforms. PMID- 27249821 TI - Improvement of Long-Jump Performance During Competition Using a Plyometric Exercise. AB - PURPOSE: To examine the acute effects of a conditioning plyometric exercise on long-jump performance during a simulated long-jump competition. METHODS: Eight national-level track and field decathletes performed 6 long-jump attempts with a full approach run separated by 10-min recoveries. In the experimental condition subjects performed 3 rebound vertical jumps with maximal effort 3 min before the last 5 attempts, while the 1st attempt served as baseline. In the control condition the participants performed 6 long jumps without executing the conditioning exercise. RESULTS: Compared with baseline, long-jump performance progressively increased only in the experimental condition, from 3.0%, or 17.5 cm, in the 3rd attempt (P = .046, d = 0.56), to 4.8%, or 28.2 cm, in the 6th attempt (P = .0001, d = 0.84). The improvement in long-jump performance was due to a gradual increase in vertical takeoff velocity from the 3rd (by 8.7%, P = .0001, d = 1.82) to the 6th jump (by 17.7%, P = .0001, d = 4.38). Horizontal approach velocity, takeoff duration, and horizontal velocity at takeoff were similar at all long-jump attempts in both conditions (P = .80, P = .36, and P = .15, respectively). CONCLUSIONS: Long-jump performance progressively improved during a simulated competition when a plyometric conditioning exercise was executed 3 min before each attempt. This improvement was due to a progressive increase in vertical velocity of takeoff, while there was no effect on the horizontal velocity. PMID- 27249822 TI - An Automatic User-Adapted Physical Activity Classification Method Using Smartphones. AB - In recent years, an increasing number of people have become concerned about their health. Most chronic diseases are related to lifestyle, and daily activity records can be used as an important indicator of health. Specifically, using advanced technology to automatically monitor actual activities can effectively prevent and manage chronic diseases. The data used in this paper were obtained from acceleration sensors and gyroscopes integrated in smartphones. We designed an efficient Adaboost-Stump running on a smartphone to classify five common activities: cycling, running, sitting, standing, and walking and achieved a satisfactory classification accuracy of 98%. We designed an online learning method, and the classification model requires continuous training with actual data. The parameters in the model then become increasingly fitted to the specific user, which allows the classification accuracy to reach 95% under different use environments. In addition, this paper also utilized the OpenCL framework to design the program in parallel. This process can enhance the computing efficiency approximately ninefold. PMID- 27249823 TI - Mitigation of Intra-coil Eddy Currents in Split Gradient Coils in a Hybrid MRI LINAC System. AB - OBJECTIVE: The aim of this study is to mitigate intra-gradient coil eddy currents in a hybrid MRI-LINAC system. METHODS: The tracks of the gradient coils are modified by cutting slits along the current flow direction. The electromagnetic model developed was first experimentally validated and then used to study the impacts of the slit conductors on the energized and surrounding coils. In this study, gradient coils were slit with different numbers of sub-tracks and driven by a current with frequencies ranging from 100 Hz to 10 kHz. The proposed configuration was assessed by evaluating a number of system parameters, such as the gradient magnetic field, the power loss generated in the surrounding unenergized coil (hereafter referred to as passive coils), and the performance of the energized coil. RESULTS: It was found that at a typical operating frequency of 1 kHz and compared with a conventional (no cut) split coil structure, the new coil pattern (with four slits) offered improved coil parameters. 1) The average power loss dissipated in the surrounding passive coil was significantly reduced by 85%, 2) the cuts largely reduced the secondary field generated by the eddy currents in the passive coil, which was reduced to about 4% of that produced by the uncut coil and, 3) the performance of the energized coil with slit tracks was significantly improved. Some typical gradient coil parameters, such as the figure of merit, efficiency (eta), and eta2/R (where eta is the efficiency and R is the resistance), were improved by 8.0%, 11.9%, and 45.7%, respectively. CONCLUSION AND SIGNIFICANCE: The new slit coil structure is effective in mitigating intra coil eddy current effects, which is an important issue in the MRI-LINAC system. PMID- 27249824 TI - A Novel Quantitative 500-MHz Acoustic Microscopy System for Ophthalmologic Tissues. AB - OBJECTIVE: This paper describes development of a novel 500-MHz scanning acoustic microscope (SAM) for assessing the mechanical properties of ocular tissues at fine resolution. The mechanical properties of some ocular tissues, such as lamina cribrosa (LC) in the optic nerve head, are believed to play a pivotal role in eye pathogenesis. METHODS: A novel etching technology was used to fabricate silicon based lens for a 500-MHz transducer. The transducer was tested in a custom designed scanning system on human eyes. Two-dimensional (2-D) maps of bulk modulus (K) and mass density (rho) were derived using improved versions of current state-of-the-art signal processing approaches. RESULTS: The transducer employed a lens radius of 125 MUm and had a center frequency of 479 MHz with a -6 dB bandwidth of 264 MHz and a lateral resolution of 4 MUm. The LC, Bruch's membrane (BM) at the interface of the retina and choroid, and Bowman's layer (BL) at the interface of the corneal epithelium and stroma, were successfully imaged and resolved. Analysis of the 2-D parameter maps revealed average values of LC, BM, and BL with KLC = 2.81 +/-0.17; GPa, KBM = 2.89 +/-0.18; GPa, KBL = 2.6 +/ 0.09 ; GPa, rho LC = 0.96 +/-0.03 g/cm3; rho BM = 0.97 +/-0.04 g/cm3; rho BL = 0.98 +/-0.04 g/cm3. SIGNIFICANCE: This novel SAM was shown to be capable of measuring mechanical properties of soft biological tissues at microscopic resolution; it is currently the only system that allows simultaneous measurement of K, rho, and attenuation in large lateral scales (field area >9 mm2) and at fine resolutions. PMID- 27249826 TI - Review: Mechanical Characterization of Carotid Arteries and Atherosclerotic Plaques. AB - Cardiovascular disease (CVD) is a leading cause of death and is in the majority of cases due to the formation of atherosclerotic plaques in arteries. Initially, thickening of the inner layer of the arterial wall occurs. Continuation of this process leads to plaque formation. The risk of a plaque to rupture and thus to induce an ischemic event is directly related to its composition. Consequently, characterization of the plaque composition and its proneness to rupture are of crucial importance for risk assessment and treatment strategies. The carotid is an excellent artery to be imaged with ultrasound because of its superficial position. In this review, ultrasound-based methods for characterizing the mechanical properties of the carotid wall and atherosclerotic plaque are discussed. Using conventional echography, the intima media thickness (IMT) can be quantified. There is a wealth of studies describing the relation between IMT and the risk for myocardial infarction and stroke. Also the carotid distensibility can be quantified with ultrasound, providing a surrogate marker for the cross sectional mechanical properties. Although all these parameters are associated with CVD, they do not easily translate to individual patient risk. Another technique is pulse wave velocity (PWV) assessment, which measures the propagation of the pressure pulse over the arterial bed. PWV has proven to be a marker for global arterial stiffness. Recently, an ultrasound-based method to estimate the local PWV has been introduced, but the clinical effectiveness still needs to be established. Other techniques focus on characterization of plaques. With ultrasound elastography, the strain in the plaque due to the pulsatile pressure can be quantified. This technique was initially developed using intravascular catheters to image coronaries, but recently noninvasive methods were successfully developed. A high correlation between the measured strain and the risk for rupture was established. Acoustic radiation force impulse (ARFI) imaging also provides characterization of local plaque components based on mechanical properties. However, both elastography and ARFI provide an indirect measure of the elastic modulus of tissue. With shear wave imaging, the elastic modulus can be quantified, although the carotid artery is one of the most challenging tissues for this technique due to its size and geometry. Prospective studies still have to establish the predictive value of these techniques for the individual patient. Validation of ultrasound-based mechanical characterization of arteries and plaques remains challenging. Magnetic resonance imaging is often used as the "gold" standard for plaque characterization, but its limited resolution renders only global characterization of the plaque. CT provides information on the vascular tree, the degree of stenosis, and the presence of calcified plaque, while soft plaque characterization remains limited. Histology still is the gold standard, but is available only if tissue is excised. In conclusion, elastographic ultrasound techniques are well suited to characterize the different stages of vascular disease. PMID- 27249825 TI - Optimizing Flip Angles for Metabolic Rate Estimation in Hyperpolarized Carbon-13 MRI. AB - Hyperpolarized carbon-13 magnetic resonance imaging has enabled the real-time observation of perfusion and metabolism in vivo. These experiments typically aim to distinguish between healthy and diseased tissues based on the rate at which they metabolize an injected substrate. However, existing approaches to optimizing flip angle sequences for these experiments have focused on indirect metrics of the reliability of metabolic rate estimates, such as signal variation and signal to-noise ratio. In this paper we present an optimization procedure that focuses on maximizing the Fisher information about the metabolic rate. We demonstrate through numerical simulation experiments that flip angles optimized based on the Fisher information lead to lower variance in metabolic rate estimates than previous flip angle sequences. In particular, we demonstrate a 20% decrease in metabolic rate uncertainty when compared with the best competing sequence. We then demonstrate appropriateness of the mathematical model used in the simulation experiments with in vivo experiments in a prostate cancer mouse model. While there is no ground truth against which to compare the parameter estimates generated in the in vivo experiments, we demonstrate that our model used can reproduce consistent parameter estimates for a number of flip angle sequences. PMID- 27249827 TI - JPL Ultrastable Trapped Ion Atomic Frequency Standards. AB - Recently, room temperature trapped ion atomic clock development at the Jet Propulsion Laboratory (JPL) has focused on three directions: 1) ultrastable atomic clocks, usually for terrestrial applications emphasizing ultimate stability performance and autonomous timekeeping; 2) new atomic clock technology for space flight applications that require strict adherence to size, weight, and power requirements; and 3) miniature clocks. In this paper, we concentrate on the first direction and present a design and the initial results from a new ultrastable clock referred to as L10 that achieves a short-term stability of 4.5 *10(-14)/tau(1/2) and an initial measurement of no significant drift with an uncertainty of 2.4 *10(-16) /day over a two-week period. PMID- 27249828 TI - Coded Spectral Doppler Imaging: From Simulation to Real-Time Processing. AB - Transmission of coded pulses and matched receive filtering can improve the ultrasound imaging penetration depth while preserving the axial resolution. This paper shows that the pulse compression technique may be integrated in a low-cost scanner to be profitably used also in spectral Doppler investigations. By operating on beamformed, demodulated, and down-sampled data in the frequency domain, a single digital signal processor is proved sufficient to perform both pulse compression and multigate spectral Doppler algorithms in real time. Simulations, phantom, and in vivo experiments demonstrate that the transmission of (2.5 or [Formula: see text] long) linear frequency-modulated chirps with bandwidths over the range 1.6-5.4 MHz, rather than of corresponding sine-burst pulses, provides signal-to-noise ratio (SNR) improvements very close to theory. Even in the presence of selective tissue attenuation, SNR gains up to 11 and 13.3 dB have been obtained for the short and the longer chirp, respectively. This may be important in clinical Doppler applications where the needed penetration depth is not achieved with sufficient SNR unless very long bursts are transmitted. PMID- 27249829 TI - Image Zoom Completion. AB - We consider the problem of recovering a high-resolution image from a pair consisting of a complete low-resolution image and a high-resolution but incomplete one. We refer to this task as the image zoom completion problem. After discussing possible contexts in which this setting may arise, we introduce a nonlocal regularization strategy, giving full details concerning the numerical optimization of the corresponding energy and discussing its benefits and shortcomings. We also derive two total variation-based algorithms and evaluate the performance of the proposed methods on a set of natural and textured images. We compare the results and get with those obtained with two recent state-of-the art single-image super-resolution algorithms. PMID- 27249830 TI - Dual Diversified Dynamical Gaussian Process Latent Variable Model for Video Repairing. AB - In this paper, we propose a dual diversified dynamical Gaussian process latent variable model ( [Formula: see text]GPLVM) to tackle the video repairing issue. For preservation purposes, videos have to be conserved on media. However, storing on media, such as films and hard disks, can suffer from unexpected data loss, for instance, physical damage. So repairing of missing or damaged pixels is essential for better video maintenance. Most methods seek to fill in missing holes by synthesizing similar textures from local patches (the neighboring pixels), consecutive frames, or the whole video. However, these can introduce incorrect contexts, especially when the missing hole or number of damaged frames is large. Furthermore, simple texture synthesis can introduce artifacts in undamaged and recovered areas. To address aforementioned problems, we introduce two diversity encouraging priors to both of inducing points and latent variables for considering the variety in existing videos. In [Formula: see text]GPLVM, the inducing points constitute a smaller subset of observed data, while latent variables are a low-dimensional representation of observed data. Since they have a strong correlation with the observed data, it is essential that both of them can capture distinct aspects of and fully represent the observed data. The dual diversity encouraging priors ensure that the trained inducing points and latent variables are more diverse and resistant for context-aware and artifacts-free based video repairing. The defined objective function in our proposed model is initially not analytically tractable and must be solved by variational inference. Finally, experimental testing results illustrate the robustness and effectiveness of our method for damaged video repairing. PMID- 27249831 TI - Improving Intra Prediction in High-Efficiency Video Coding. AB - Intra prediction is an important tool in intra-frame video coding to reduce the spatial redundancy. In current coding standard H.265/high-efficiency video coding (HEVC), a copying-based method based on the boundary (or interpolated boundary) reference pixels is used to predict each pixel in the coding block to remove the spatial redundancy. We find that the conventional copying-based method can be further improved in two cases: 1) the boundary has an inhomogeneous region and 2) the predicted pixel is far away from the boundary that the correlation between the predicted pixel and the reference pixels is relatively weak. This paper performs a theoretical analysis of the optimal weights based on a first-order Gaussian Markov model and the effects when the pixel values deviate from the model and the predicted pixel is far away from the reference pixels. It also proposes a novel intra prediction scheme based on the analysis that smoothing the copying-based prediction can derive a better prediction block. Both the theoretical analysis and the experimental results show the effectiveness of the proposed intra prediction method. An average gain of 2.3% on all intra coding can be achieved with the HEVC reference software. PMID- 27249832 TI - Super-Resolution of Dynamic Scenes Using Sampling Rate Diversity. AB - In earlier work, we proposed a super-resolution (SR) method that required the availability of two low resolution (LR) sequences corresponding to two different sampling rates, where images from one sequence were used as a basis to represent the polyphase components (PPCs) of the high resolution (HR) image, while the other LR sequences provided the reference LR image (to be super-resolved). The (simple) algorithm implemented by Salem and Yagle is only applicable when the scene is static. In this paper, we recast our approach to SR as a two-stage example-based algorithm to process dynamic scenes. We employ feature selection to create, from the LR frames, local LR dictionaries to represent PPCs of HR patches. To enforce sparsity, we implement Gaussian generative models as an efficient alternative to L1-norm minimization. Estimation errors are further reduced using what we refer to as the anchors, which are based on the relationship between PPCs corresponding to different sampling rates. In the second stage, we revert to simple single frame SR (applied to each frame), using HR dictionaries extracted from the super-resolved sequence of the previous stage. The second stage is thus a reiteration of the sparsity coding scheme, using only one LR sequence, and without involving PPCs. The ability of the modified algorithm to super-resolve challenging LR sequences reintroduces sampling rate diversity as a prerequisite of robust multiframe SR. PMID- 27249833 TI - PiCode: A New Picture-Embedding 2D Barcode. AB - Nowadays, 2D barcodes have been widely used as an interface to connect potential customers and advertisement contents. However, the appearance of a conventional 2D barcode pattern is often too obtrusive for integrating into an aesthetically designed advertisement. Besides, no human readable information is provided before the barcode is successfully decoded. This paper proposes a new picture-embedding 2D barcode, called PiCode, which mitigates these two limitations by equipping a scannable 2D barcode with a picturesque appearance. PiCode is designed with careful considerations on both the perceptual quality of the embedded image and the decoding robustness of the encoded message. Comparisons with the existing beautified 2D barcodes show that PiCode achieves one of the best perceptual qualities for the embedded image, and maintains a better tradeoff between image quality and decoding robustness in various application conditions. PiCode has been implemented in the MATLAB on a PC and some key building blocks have also been ported to Android and iOS platforms. Its practicality for real-world applications has been successfully demonstrated. PMID- 27249834 TI - Just Noticeable Difference Estimation for Screen Content Images. AB - We propose a novel just noticeable difference (JND) model for a screen content image (SCI). The distinct properties of the SCI result in different behaviors of the human visual system when viewing the textual content, which motivate us to employ a local parametric edge model with an adaptive representation of the edge profile in JND modeling. In particular, we decompose each edge profile into its luminance, contrast, and structure, and then evaluate the visibility threshold in different ways. The edge luminance adaptation, contrast masking, and structural distortion sensitivity are studied in subjective experiments, and the final JND model is established based on the edge profile reconstruction with tolerable variations. Extensive experiments are conducted to verify the proposed JND model, which confirm that it is accurate in predicting the JND profile, and outperforms the state-of-the-art schemes in terms of the distortion masking ability. Furthermore, we explore the applicability of the proposed JND model in the scenario of perceptually lossless SCI compression, and experimental results show that the proposed scheme can outperform the conventional JND guided compression schemes by providing better visual quality at the same coding bits. PMID- 27249835 TI - In Vivo Estimation of Human Forearm and Wrist Dynamic Properties. AB - It is important to estimate the 3 degree-of-freedom (DOF) impedance of human forearm and wrist (i.e., forearm prono-supination, and wrist flexion-extension and radial-ulnar deviation) in motor control and in the diagnosis of altered mechanical resistance following stroke. There is, however, a lack of methods to characterize 3 DOF impedance. Thus, we developed a reliable and accurate impedance estimation method, the distal internal model based impedance control (dIMBIC)-based method, to characterize the 3 DOF impedance, including cross coupled terms between DOFs, for the first time. Its accuracy and reliability were experimentally validated using a robot with substantial nonlinear joint friction. The 3 DOF human forearm and wrist impedance of eight healthy subjects was reliably characterized, and its linear behavior was verified. Thus, the dIMBIC based method can provide us with 3 DOF forearm and wrist impedance regardless of nonlinear robot joint friction. It is expected that, with the proposed method, the 3 DOF impedance estimation can promote motor control studies and complement the diagnosis of altered wrist and forearm resistance post-stroke by providing objective impedance estimates, including cross-coupled terms. PMID- 27249836 TI - An Insect Eye Inspired Miniaturized Multi-Camera System for Endoscopic Imaging. AB - In this work, we present a miniaturized high definition vision system inspired by insect eyes, with a distributed illumination method, which can work in dark environments for proximity imaging applications such as endoscopy. Our approach is based on modeling biological systems with off-the-shelf miniaturized cameras combined with digital circuit design for real time image processing. We built a 5 mm radius hemispherical compound eye, imaging a 180 degrees *180 degrees degrees field of view while providing more than 1.1 megapixels (emulated ommatidias) as real-time video with an inter-ommatidial angle ?phi = 0.5 degrees at 18 mm radial distance. We made an FPGA implementation of the image processing system which is capable of generating 25 fps video with 1080 * 1080 pixel resolution at a 120 MHz processing clock frequency. When compared to similar size insect eye mimicking systems in literature, the system proposed in this paper features 1000 * resolution increase. To the best of our knowledge, this is the first time that a compound eye with built-in illumination idea is reported. We are offering our miniaturized imaging system for endoscopic applications like colonoscopy or laparoscopic surgery where there is a need for large field of view high definition imagery. For that purpose we tested our system inside a human colon model. We also present the resulting images and videos from the human colon model in this paper. PMID- 27249837 TI - Review on Lithotripsy and Cavitation in Urinary Stone Therapy. AB - Cavitation is the sudden formation of vapor bubbles or voids in liquid media and occurs after rapid changes in pressure as a consequence of mechanical forces. It is mostly an undesirable phenomenon. Although the elimination of cavitation is a major topic in the study of fluid dynamics, its destructive nature could be exploited for therapeutic applications. Ultrasonic and hydrodynamic sources are two main origins for generating cavitation. The purpose of this review is to give the reader a general idea about the formation of cavitation phenomenon and existing biomedical applications of ultrasonic and hydrodynamic cavitation. Because of the high number of the studies on ultrasound cavitation in the literature, the main focus of this review is placed on the lithotripsy techniques, which have been widely used for the treatment of urinary stones. Accordingly, cavitation phenomenon and its basic concepts are presented in Section II. The significance of the ultrasound cavitation in the urinary stone treatment is discussed in Section III in detail and hydrodynamic cavitation as an important alternative for the ultrasound cavitation is included in Section IV. Finally, side effects of using both ultrasound and hydrodynamic cavitation in biomedical applications are presented in Section V. PMID- 27249838 TI - Effects of Grip-Force, Contact, and Acceleration Feedback on a Teleoperated Pick and-Place Task. AB - The multifaceted human sense of touch is fundamental to direct manipulation, but technical challenges prevent most teleoperation systems from providing even a single modality of haptic feedback, such as force feedback. This paper postulates that ungrounded grip-force, fingertip-contact-and-pressure, and high-frequency acceleration haptic feedback will improve human performance of a teleoperated pick-and-place task. Thirty subjects used a teleoperation system consisting of a haptic device worn on the subject's right hand, a remote PR2 humanoid robot, and a Vicon motion capture system to move an object to a target location. Each subject completed the pick-and-place task 10 times under each of the eight haptic conditions obtained by turning on and off grip-force feedback, contact feedback, and acceleration feedback. To understand how object stiffness affects the utility of the feedback, half of the subjects completed the task with a flexible plastic cup, and the others used a rigid plastic block. The results indicate that the addition of grip-force feedback with gain switching enables subjects to hold both the flexible and rigid objects more stably, and it also allowed subjects who manipulated the rigid block to hold the object more delicately and to better control the motion of the remote robot's hand. Contact feedback improved the ability of subjects who manipulated the flexible cup to move the robot's arm in space, but it deteriorated this ability for subjects who manipulated the rigid block. Contact feedback also caused subjects to hold the flexible cup less stably, but the rigid block more securely. Finally, adding acceleration feedback slightly improved the subject's performance when setting the object down, as originally hypothesized; interestingly, it also allowed subjects to feel vibrations produced by the robot's motion, causing them to be more careful when completing the task. This study supports the utility of grip-force and high frequency acceleration feedback in teleoperation systems and motivates further improvements to fingertip-contact-and-pressure feedback. PMID- 27249839 TI - Iterative Adaptive Dynamic Programming for Solving Unknown Nonlinear Zero-Sum Game Based on Online Data. AB - Hinfinity control is a powerful method to solve the disturbance attenuation problems that occur in some control systems. The design of such controllers relies on solving the zero-sum game (ZSG). But in practical applications, the exact dynamics is mostly unknown. Identification of dynamics also produces errors that are detrimental to the control performance. To overcome this problem, an iterative adaptive dynamic programming algorithm is proposed in this paper to solve the continuous-time, unknown nonlinear ZSG with only online data. A model free approach to the Hamilton-Jacobi-Isaacs equation is developed based on the policy iteration method. Control and disturbance policies and value are approximated by neural networks (NNs) under the critic-actor-disturber structure. The NN weights are solved by the least-squares method. According to the theoretical analysis, our algorithm is equivalent to a Gauss-Newton method solving an optimization problem, and it converges uniformly to the optimal solution. The online data can also be used repeatedly, which is highly efficient. Simulation results demonstrate its feasibility to solve the unknown nonlinear ZSG. When compared with other algorithms, it saves a significant amount of online measurement time. PMID- 27249843 TI - Rigidity-Based Multiagent Layered Formation Control. AB - This paper provides a solution to the nonplanar multiagent formation control problem using graph rigidity. We consider a 3-D multiagent formation control where multiple agents are operating in one plane and some other agents are operating outside of that plane. This can be referred to as a layered formation control where the objective is for all agents to cooperatively acquire a predefined formation shape using a decentralized control law. The proposed control strategy is based on regulating the interagent distances. A rigorous stability analysis is presented that guarantees convergence of these distances to desired values. Simulation results are presented to support the theoretical results. PMID- 27249840 TI - Low-Power Wearable Systems for Continuous Monitoring of Environment and Health for Chronic Respiratory Disease. AB - We present our efforts toward enabling a wearable sensor system that allows for the correlation of individual environmental exposures with physiologic and subsequent adverse health responses. This system will permit a better understanding of the impact of increased ozone levels and other pollutants on chronic asthma conditions. We discuss the inefficiency of existing commercial off the-shelf components to achieve continuous monitoring and our system-level and nano-enabled efforts toward improving the wearability and power consumption. Our system consists of a wristband, a chest patch, and a handheld spirometer. We describe our preliminary efforts to achieve a submilliwatt system ultimately powered by the energy harvested from thermal radiation and motion of the body with the primary contributions being an ultralow-power ozone sensor, an volatile organic compounds sensor, spirometer, and the integration of these and other sensors in a multimodal sensing platform. The measured environmental parameters include ambient ozone concentration, temperature, and relative humidity. Our array of sensors also assesses heart rate via photoplethysmography and electrocardiography, respiratory rate via photoplethysmography, skin impedance, three-axis acceleration, wheezing via a microphone, and expiratory airflow. The sensors on the wristband, chest patch, and spirometer consume 0.83, 0.96, and 0.01 mW, respectively. The data from each sensor are continually streamed to a peripheral data aggregation device and are subsequently transferred to a dedicated server for cloud storage. Future work includes reducing the power consumption of the system-on-chip including radio to reduce the entirety of each described system in the submilliwatt range. PMID- 27249841 TI - Integrative Analysis of Proteomic, Glycomic, and Metabolomic Data for Biomarker Discovery. AB - Studies associating changes in the levels of multiple biomolecules including proteins, glycans, glycoproteins, and metabolites with the onset of cancer have been widely investigated to identify clinically relevant diagnostic biomarkers. Advances in liquid or gas chromatography mass spectrometry (LC-MS, GC-MS) have enabled high-throughput qualitative and quantitative analysis of these biomolecules. While results from separate analyses of different biomolecules have been reported widely, the mutual information obtained by partly or fully combining them has been relatively unexplored. In this study, we investigate integrative analysis of proteins, N-glycans, and metabolites to take advantage of complementary information to improve the ability to distinguish cancer cases from controls. Specifically, support vector machine-recursive feature elimination algorithm is utilized to select a panel of proteins, N-glycans, and metabolites based on LC-MS and GC-MS data previously acquired by the analysis of blood samples from two cohorts in a liver cancer study. Improved performances are observed by integrative analysis compared to separate proteomic, glycomic, and metabolomic studies in distinguishing liver cancer cases from patients with liver cirrhosis. PMID- 27249844 TI - Output Feedback Control and Stabilization for Networked Control Systems With Packet Losses. AB - This paper mainly considers the optimal measurement feedback control and stabilization for networked control systems (NCSs) with packet losses. The problems are involved with fundamental difficulties of separation principle and optimal estimation (conditional expectation) for multiplicative noise stochastic systems. First, the optimal estimator (conditional expectation) for NCSs with packet losses is derived and the optimal measurement feedback controller is obtained by using the maximum principle. The sufficient and necessary solvability condition of finite horizon measurement feedback control problem is first presented. Moreover, the asymptotic stability of the optimal estimator is studied. Finally, for the infinite horizon case, based on the introduction of a new Lyapunov function, which is defined with the optimal cost function, it is shown that the system is stabilizable in the mean square sense if and only if an algebraic Riccati equation admits a unique positive definite solution. PMID- 27249845 TI - Person Reidentification in a Distributed Camera Network Framework. AB - Plenty of research has been conducted to obtain the best reidentification performance between a single camera-pairs. None of the current approaches has addressed the reidentification in a camera network by considering the network topology (i.e., the structure of the monitored environment). We introduce a distributed network person reidentification framework which introduces the following contributions. 1) a camera matching cost to measure the reidentification performance between nodes of the network and 2) a derivation of the distance vector algorithm which allows to learn the network topology thus to prioritize and limit the cameras inquired for the matching of the probe. Results on three benchmark datasets show that the network topology can be learned in an unsupervised fashion and network-wise reidentification performance improves. As a side effect, we obtain that the communication bandwidth usage is reduced. PMID- 27249846 TI - Active Complementary Control for Affine Nonlinear Control Systems With Actuator Faults. AB - This paper is concerned with the problem of active complementary control design for affine nonlinear control systems with actuator faults. The outage and loss of effectiveness fault cases are considered. In order to achieve the performance enhancement of the faulty control system, the complementary control scheme is designed in two steps. Firstly, a novel fault estimation scheme is developed. Then, by using the fault estimations to reconstruct the faulty system dynamics and introducing a cost function as the optimization objective, a nearly optimal complementary control is obtained online based on the adaptive dynamic programming (ADP) method. Unlike most of the previous ADP methods with the addition of a probing signal, new adaptive weight update laws are derived to guarantee the convergence of neural network weights and the stability of the closed-loop system, which strongly supports the online implementation of the ADP method. Finally, two simulation examples are given to illustrate the performance and effectiveness of the proposed method. PMID- 27249847 TI - Is dental caries a multifactorial disease? Likely not! PMID- 27249848 TI - Freezing and fractionation: effects of preservation on carbon and nitrogen stable isotope ratios of some limnetic organisms. AB - RATIONALE: Stable isotopes of carbon and nitrogen have become important natural tracers for studying food-web structure and function. Considerable research has demonstrated that chemical preservatives and fixatives shift the isotopic ratios of aquatic organisms. Much less is known about the effects of freezing as a preservation method although this technique is commonly used. METHODS: We conducted a controlled experiment to test the effects of freezing (-10 degrees C) and flash freezing (-79 degrees C) on the carbon and nitrogen isotope ratios of zooplankton (Cladocera), Mysis diluviana and Rainbow Trout (Oncorhynchus mykiss). Subsamples (~0.5 mg) of dried material were analyzed for percentage carbon, percentage nitrogen, and the relative abundance of stable carbon and nitrogen isotopes (delta13C and delta15N values) using a Carlo Erba NC2500 elemental analyzer interfaced to a ThermoFinnigan MAT Delta Plus isotope ratio mass spectrometer. RESULTS: The effects of freezing were taxon-dependent. Freezing had no effect on the isotopic or elemental values of Rainbow Trout muscle. Effects on the delta13C and delta15N values of zooplankton and Mysis were statistically significant but small relative to typical values of trophic fractionation. The treatment-control offsets had larger absolute values for Mysis (delta13C: <=0.76 +/- 0.410/00, delta15N: <=0.37 +/- 0.160/00) than for zooplankton (delta13C: <=0.12 +/- 0.060/00, delta15N: <=0.30 +/- 0.270/00). The effects of freezing were more variable for the delta13C values of Mysis, and more variable for the delta15N values of zooplankton. Generally, both freezing methods reduced the carbon content of zooplankton and Mysis, but freezing had a negative effect on the %N of zooplankton and a positive effect on the %N of Mysis. CONCLUSIONS: The species-dependencies and variability of freezing effects on aquatic organisms suggest that more research is needed to understand the mechanisms responsible for freezing-related fractionation before standardized protocols for freezing as a preservation method can be adopted. PMID- 27249849 TI - [Strategy for anti-HBV therapy in women of childbearing age and pregnancy]. PMID- 27249850 TI - [Pregnancy-related factors and antiviral treatment for chronic hepatitis B]. PMID- 27249851 TI - [Indications and opportunities for antiviral therapy to treat chronic HBV infection in women of childbearing age and during pregnancy]. PMID- 27249852 TI - THE VISION CONTINUES.... PMID- 27249853 TI - PATIENT'S PAGE. COMMON MYTHS OF GUM DISEASE. PMID- 27249854 TI - L.D. WHITLOCK, DDS ODA PRESIDENT 1987-88. PMID- 27249855 TI - Leaving a Legacy. PMID- 27249856 TI - Somebody is watching you (or your customer service anyway). PMID- 27249857 TI - [COMPETENCE OF INTRALUMINAL ENDOSCOPY SPECIALISTS: PROSPECTS AND CHALLENGES]. AB - This article shows the current status of the establishment of endoscopists in Kazakhstan, the need for which have grown because of implementation of a population-based screening for colorectal cancer and a screening pilot project to detect cancer of esophagus and stomach. Also the article reflects the opportunities and problems of the educational process, compares the world experience in this field with real situation in Kazakhstan. PMID- 27249858 TI - [OPTICAL BIOPSY FOR DIAGNOSIS OF ESOPHAGEAL MUCOSAL CHANGES IN CHILDREN]. AB - AIM: To analyze the value of confocal laser endomicroscopy in diagnostics of upper gastrointestinal tract mucosa changes in children. PATIENTS AND METHODS: In the current study a total of 116 children aged from 3 to 18 years old undergo conventional endoscopy with confocal laser endomicroscopy supplemented with mucosal biopsy followed by traditional histology in the period from 2011 until 2014. To determine the prognostic value of the of probe based CLE in the evaluation of normal and pathological changes of the esophageal mucosa a comparison of results of optical biopsy with the data obtained during the standard histological examination were performed. RESULTS: After results of probe based CLE and traditional histology were comprised optical biopsy showed 88.8% sensitivity and 88.3% specificity to esophagitis with Spearmen correlation 0.79 (p = 0.001); 92.3% sensitivity and 95.3% specificity to metaplastic changes of esophageal mucosa with Spearmen correlation 0.85 (p = 0.001); 92.4% sensitivity and 95.2% specificity in differential diagnosis of esophageal polyps with Spearmen correlation 0.95 (p = 0.001). CONCLUSION: Confocal endomicroscopy may become one of the leading methods in pediatric gastroenterology since it allows the endoscopists to inspect the mucosa at the cellular level during the endoscopic procedure and can help in establishing the diagnosis. PMID- 27249859 TI - [MEDICAL-DIAGNOSTIC ALGORITM IN BARRETT'S ESOPHAGUS]. AB - Aim of study was determination of effectiveness of endoscopic argon plasma coagulation and oxide of nitrogen in the treatment of Barretts esophagus. MATERIALS AND METHODS: Results of using argon plasma coagulation and oxide of nitrogen in the treatment of 26 patients with Barretts esophagus. RESULTS: It was shown that argon plasma coagulation is very effective and safe method for endoscopic treatment of Barretts esophagus. Ablation of short and long segment of Barretts esophagus is completed in all cases, but it requires follow up and biopsy. Oxide of nitrogen in the speed up process of epythelisation. PMID- 27249860 TI - [THE CLINICAL SIGNIFICANCE OF ENDOSCOPIC MANOMETROGRAPHY OF UPPER GASTROINTESTINAL TRACT IN PATIENTS WITH CHRONIC PANCREATITIS]. AB - THE PURPOSE OF THE RESEARCH: To study the cavitary esophagogastroduodenal pressure in patients with chronic pancreatitis (CP) depending on the dominant clinical symptoms--gastroesophageal reflux (GER) and abdominal pancreatic pain. MATERIAL AND METHODS: By esophagogastroduodenoscopy that included manometrography and acid-perfusion test--were examined 86 patients with CP and 25 healthy individuals. RESULTS: 63% of patients with CP detected changes of the esophagus and the lower esophageal sphincter (LES) based on the endoscopy, or manometrography, or test with 0.1N hydrochloric acid solution. The presence of GER compared with its absence in patients with CP was associated with significantly lower rates LES pressure and pressure gradients between the LES and antral stomach and between the LES and duodenum. Patients with CP with leading pancreatic abdominal pain syndrome compared with patients with GER signs and without GER signs were found the lowest pressure LES and pressure gradients between the LES and the pyloric stomach, LES and the duodenum. The presence of heartburn in patients with CP without erosive esophagitis found correlative connection with positive endoscopic acid-perfusion test and the pressure drop in the LES. CONCLUSION: Integrated upper endoscopy, including endoscopic manometrography and esophageal acid-perfusion test in clinical studies increases the frequency of detection of non-erosive reflux disease and one of its predictors--reduced esophago-gastric pressure gradient. PMID- 27249861 TI - [COLON CAPSULE ENDOSCOPY IN CLINICAL EXPERIENCE]. AB - AIM: Is to evaluate technical aspects and feasibility of colon capsule endoscopy (CCE) in the daily clinical practice. MATERIALS AND METHODS: From I.2014 to VIII.2014 we performed 36 (97.3%) CCE from 37 patients (m-19, f-17, mean age 43.9 +/- 14.2 years, range 22-72). RESULTS: Total CCE was performed in 33 (89.2%) patients. In all patients we were able to register anatomy and to evaluate the lumen and the wall of large bowel; to explore and identify mucosal abnormality as well as epithelial lesions. CONCLUSION: The article demonstrates our own experience of colon capsule endoscopy (n = 36); the principal possibilities to evaluate colon anatomy and to detect wide range of abnormality. PMID- 27249862 TI - [APPLICATION OF HD-VIDEOENDOSCOPY, MAGNIFYING ENDOSCOPY AND NARROW BAND IMAGING TECHNIQUE FOR THE DIFFERENTIAL DIAGNOSIS OF BENIGN AND NEOPLASTIC EPITHELIAL LESIONS IN THE STOMACH. THE POTENTIAL OF THE COMPUTER-AIDED ANALYSIS]. AB - An endoscopic diagnosis of superficial epithelial neoplastic gastric lesions and early gastric cancer is the challenge of medicine today. It remains at a low level without the use of modern endoscopic technologies such as HDTV and magnifying endoscopy, narrow band imaging (NBI) and similar image-enhanced endoscopic methods, which provide the visualization of microsurface and microvascular pattern. There are a few endoscopic classifications of microsurface and microvascular patterns to distinguish benign and neoplastic superficial gastric epithelial lesions. However, the most effective classifications are based on the intuitive analysis of regularity of surface or/and vascular pattern or heterogeneity of vessels shape and thickness. They are complex for understanding and learning to inexperienced specialists. In this study, we performed expert and computer analysis of 104 HDTV and magnifying NBI endoscopic images of benign and neoplastic gastric lesions in parallel. The images were described for 7 clinical and 23 endoscopic parameters, including 12 qualitative parameters of microsurface and microvascular patterns by the expert evaluation. After statistical analysis, the significant parameters were defined, and the decision rule for the differential diagnosis of benign and malignant lesions were composed. An accuracy of the decision rule was 95.8% for selection of benign lesions and 81.8% for epithelial neoplasia. We performed the computer-aided image analysis using a method "bag of visual words" to distinguish endoscopic images based on irregular vascular pattern as the most significant parameter in expert image analysis and we have shown the accuracy 73-78% for this method. We plan to use this method for independent computer-aided analysis of endoscopic images for differentiation of benign and neoplastic epithelial gastric lesions and creating the clinical decision support system for endoscopy. PMID- 27249863 TI - [ENDOSCOPIC GASTRODUODENAL AND ENTERAL STENTING OF MALIGNANT STENOSES: INDICATIONS, TECHNIQUE, RESULTS]. PMID- 27249864 TI - [RADICAL ENDOSCOPIC REMOVAL OF ADENOMA OF THE MAJOR DUODENAL PAPILLA WITH SUCCESSFUL INTRAOPERATIVE CORRECTION OF COMPLICATIONS]. AB - We introduce one of the successful clinical observations of a radical endoscopic removal of adenoma of the major duodenal papilla with severe dysplasia, as well as intraoperative correction of complications, jet bleeding and retroduodenal perforation, which occurred during this operation. PMID- 27249865 TI - [THE FIRST CLINICAL EXPERIENCE IN THE CELIAC PLEXUS BLOCKADE UNDER ENDOSCOPIC ULTRASOUND NAVIGATION IN PATIENTS WITH PANCREATIC CANCER]. AB - OBJECTIVE: Implementation into clinical practice and getting our own data of the effectiveness of EUS-CPN in chronic pain syndrome associated with pancreatic cancer in the palliative treatment. MATERIALS AND METHODS: In the period from October 2014 to May 2015 in P.A. Herzen Moscow Research Oncological Institute- filial FGBI "NMIRC" gained the first clinical experience in the celiac plexus blockade under endoscopic ultrasound navigation in 10 patients with pain associated with pancreatic cancer. The study group included 6 women and 4 men aged 54-83 years. In 2 of 10 cases out celiac ganglia were located and injections made in side them. In eight cases, the blockade was performed after injection into the tissue surrounding the celiac trunk. In most cases, we used standard FNA needle with diameter 22G. Blockade performed by a combination of local anesthetic (3-4 ml of 0.5% bupivacaine) and 14-20 ml of 96% ethanol. RESULTS: There were no complications after EUS-BCS. 9 of 10 patients (90%) had a significant (2-4 points on a visual analogue scale) reduction of pain after 1-3 days after the procedure. These patients had a significant reduction in the frequency and dosage of analgesics. Four patients required repeat of anesthesia after 2 months--the same with a marked positive effect. One patient, in spite of the double execution of EUS-CPN did not note reduction in pain intensity. CONCLUSION: EUS-CPN procedure is highly effective, very simple and safe. It provides a high quality of life and of social adaptation oncology patients. It should be more widely used in clinical practice. PMID- 27249866 TI - [DEVELOPMENT OF FUNCTIONAL AND MORPHOLOGICAL CHANGES OF A PANCREAS DEPENDING ON THE DURATION OF OBSTRUCTIVE CHOLESTASIS]. AB - PURPOSE OF THE STUDY: To study the severity and timing of the development of functional (reversible) and morphological (irreversible) disturbances in the pancreas, depending on the duration of obstructive cholestasis. MATERIALS AND METHODS: Obstructive jaundice in the experiment 18 dogs modeled by applying the loop stranglehold on the common bile duct, followed by observation for 30 days. We measured total bilirubin and fractions aspartate aminotransferase activity (AST) and alanine aminotransferase (ALT), the contents alpha-amylase, pancreatic lipase, glucose, histological examination of the pancreas (magnification of 100 times and 400). RESULTS: On day 3 the common bile duct obstruction bilirubin increased from 7.1 to 286.8 MUmol/l, ALT--from 0.17 to 4.18 MUmol*h/l, alpha amylase from 89 to 186 U/L and lipase--to 68 to 179 U/L. Then there was a slight decrease in the parameters studied with repeated their increase to 15 hours. Morphological changes in the first three days were characterized by reversible (swelling), impaired organ that 14-16 days passed in organic (irreversible) changes. CONCLUSION: Dynamics of fluctuations in the level of liver enzymes in the pancreas and obstructive cholestasis correlates with morphological abnormalities in the pancreas and fit into the concept of general biological organism's reaction to injury. PMID- 27249867 TI - [SEROTONERGIC REGULATION OF THE DUODENUM CONTRACTIONS]. AB - The review contains an analysis of literature data on enhancement mechanisms of duodenum contractions arising during stimulation of the sympathetic trunk in the right thoracic cavity in dogs. It is established in experiments that There are mostly enhancement, not relaxation of the organ contraction occured. In this case the stimulatory effect due to the excitation of the parasympathetic fibers is excluded. The trimeperedin inhibit the serotonin receptors of autonomic ganglia neurons stimulatory activity during the nerve stimulation. It is concluded that the sympathetic trunk contain the preganglionic serotonergic nerve fibers, whose activation leads to increased bowel contractions. Direct adipinate-serotonin administration increased the bowel contraction that confirm the preganglionic serotonergic nerve fibers presence in the sympathetic trunk. The practical significance of these studies is that the new approach to the development of pharmacological agents to stimulate the motility of the gastrointestinal tract was found. The trimeperedin may inhibit the serotoninergic nerves activity that resulted in the perioperative constipation in surgical patients. Practical recommendation to exclude trimeperedin in preparing the patient for surgery to prevent perioperative constipation is formulated. PMID- 27249868 TI - [BIOLOGICAL RESERVOIRS AS A THE RESPONSE OF THE ORGANISM TO INJURY AND PROOF FOR METABOLIC CORRECTION IN GASTRODUODENAL HEMORRHAGE IN PATIENTS WITH HIGH OPERATING ANESTHETIC RISK]. AB - In the authors opinion in the process of self-regulation the human body creates some biological reservoirs in response to damage (disturbance of homeostasis) for constant internal environment In cases of decompensation and depletion of these pools metabolic correction is necessary. This opinion was based on the results of the endoscopic metabolic hemostasis in ulcer gastroduodenal bleeding in patients with high operational and anesthetic risk. PMID- 27249869 TI - [DYSFUNCTION OF THE BILIARY TRACT: DIAGNOSIS AND TREATMENT]. PMID- 27249870 TI - [THE COMBINATION OF RECURRENT INTUSSUSCEPTION DUODENAL, ZENKER DIVERTICULUM, HIATAL HERNIA AND HASTROPTOSIS AS A MANIFESTATION OF NON-DIFFERENT DYSPLASIA OF CONNECTIVE TISSUE]. AB - Presented rare clinical case: a combination of recurrent intussusception duodenal, diverticulum Zenker, hiatal hernia and hastroptosis as a manifestation of non-different dysplasia of connective tissue. Special interest is recurrent intussusception upper horizontal portion duodenal in the bulb, is not detected when esophagogastroduodenoscopy. PMID- 27249871 TI - Presidential Election and Healthcare Policy: The Last Time We Discuss This (For a While, at Least). PMID- 27249872 TI - What Practice Administrators Need to Do Today to Succeed Tomorrow. AB - Creating a high-performance culture in your medical practice does not happen overnight. For most practices, there is a divide between the structure of the practice and how the practice actually operates. Using a particular skillset and organization system to help improve overall office functions is needed in the ever-changing healthcare landscape. This article discusses how practice administrators can use actions, electronic medical records, and training to increase overall retention and create a high-performance culture in their medical practice. PMID- 27249874 TI - Avoiding Lawsuits for Wage and Hour Violations. AB - Due to the highly technical language in the wage and hour laws and regulations, employers often find that they have unknowingly violated the Fair Labor Standards Act (FLSA). This can occur because employers have improperly classified an employee as exempt or because employers do not realize that certain time should be paid in full. Improperly classifying employees as exempt or failing to compensate nonexempt employees for all time worked can lead to costly lawsuits, audits, or enforcement actions by the Wage and Hour Division of the Department of Labor. This article discusses the most common FLSA exemptions and provides best practices to avoid liability under the FLSA. PMID- 27249873 TI - Physician Reimbursement: From Fee-for-Service to MACRA, MIPS and APMs. AB - To a significant degree, "healthcare reform" is a movement to change how both physicians and healthcare facilities are compensated, with value replacing volume as the key compensation metric. The goal of this movement has not yet been accomplished, but the process is accelerating. In this article, we track how the arc of physician compensation is bending, how the Medicare Access and CHIP Reauthorization Act will drive further changes to physician compensation models, and how these changes may affect physician practice patterns and physician staffing in the future. PMID- 27249875 TI - The Changing Face of Healthcare: 2016 CPT Changes and Beyond. AB - This article reviews the changes to CPT 2016, with emphasis on the way CPT services will be provided in the future. Some of the newer codes are designed for reimbursable services provided by the medical clinical staff. In addition to the CPT changes, there are changes to the Medicare fee-for service Physician Fee Schedule. Review of these changes provides the reader with a snapshot of how healthcare will be provided and reimbursed in the future. PMID- 27249876 TI - Compliance Challenges Facing Healthcare Providers in 2016. AB - It is time to add risk analysis and risk management to your policies and procedures manuals to comply with the HIPAA Security Rules. CMS is very serious about protecting patients' health information. There is no doubt that complying just with HIPAA security is a complex undertaking, because the rules themselves have multiple elements. Create a road map that not only sees the big picture but is detailed enough to address specific concerns unique to your practice, such as identifying the right individuals in your practice to lead the effort. And finally, if you need professional help then get it--because not every practice has the time and resources needed for this effort. PMID- 27249877 TI - Assessment and Management of Work-Related Stress in Hospital Emergency Departments in Italy. AB - Recent changes in the organization of the healthcare system, triggered by the current economic crisis in Italy, require interventions aimed at minimizing the impact of work-related stress (WRS) on healthcare workers' health status and well being. Emergency department (ED) personnel appear to be particularly vulnerable to WRS as a consequence of specific occupational risk factors. The aim of this retrospective observational study was to analyze the level of WRS after improvement interventions implemented by the management staff of the ED and focused on work context factors. The assessment of WRS showed that nurses and physicians of the ED are exposed to a medium level of risk; the improvement interventions aimed at reducing WRS were focused on: (1) function and organizational culture; (2) role within the occupational organization; and (3) relationships at work policy. These interventions were found to be significantly effective in reducing the risk of WRS. PMID- 27249878 TI - End of Year Legislation; EEOC Guidance on Genetic Information; Paying for Health Insurance Under a Spouse's Plan; No Health Plan Service Provider ERISA Rights When No Assignment; Benefit Dollar Limits in 2016. PMID- 27249879 TI - The Role of Positive Psychology in the Modern Medical Practice. AB - American healthcare has been shrouded in a cloak of negativity for too long. Many doctors are more pessimistic about the state of healthcare than they were even a few decades ago. In spite of extraordinary advances in the clinical aspects of healthcare, the business side of medicine has created a downward spiral in physician spirit, resulting in unnecessary stress, zapped energy, a rise in interpersonal conflict and, ultimately and as a byproduct of this negativity, reduced patient satisfaction. This downward spiral needs to be--and can be- stemmed. This article discuss how insights from the field of positive psychology and social neuroscience can help healthcare providers and their organizations flourish, in both their professional practices and personal lives. PMID- 27249880 TI - Loneliness at the Top: Ten Ways Medical Practice Administrators Can Manage the Isolation of Leadership. AB - Medical practice.managers spend their days surrounded by people, so the last thing they may expect to feel is lonely. Yet for many, being the manager of a medical practice can lead to feelings of isolation from the rest of the staff, and loneliness. This article explores the many reasons that managing a medical practice can be a lonely business. It considers the risks when a practice manager's loneliness goes unchecked, both to the individual and to the practice. It suggests 10 effective and healthy strategies for preventing and managing the leadership loneliness that medical practice managers sometimes experience. Next, this article argues that acceptance is the first step in overcoming loneliness in the workplace. It offers guidance for medical practice managers who wish to help lonely members of their teams. It describes the benefits of having a confidant to help support the medical practice manager, and the characteristics of an ideal confidant. Finally, this article suggests a strategy for combatting loneliness by interacting with the staff more frequently. PMID- 27249881 TI - Volume of Cataract Surgery and Surgeon Gender: The Florida Ambulatory Surgery Center Experience 2005 Through 2012. AB - Cataract is the most common surgically reversible cause of vision loss and the most common major surgical procedure performed in the United States. To understand how gender composition might affect differences in health services, we examined the surgeon gender-specific rates of routine cataract surgery performed in ambulatory surgical centers in Florida. Routine cataract surgeries were identified through the Florida Agency for Health Care Administration (AHCA) ambulatory surgery center dataset. The background of individual surgeons was determined by linking license numbers in the dataset to physician profiles publicly available from AHCA. From 2005 through 2012, women ophthalmologists in Florida performed roughly half the annual rate of cataract surgery as their male counterparts. This difference is not explained by greater time in clinical practice for men. Further investigation into the causes of this gender-volume disparity is warranted to determine what roles choice and barriers may play. PMID- 27249882 TI - Make It So--Engage! PMID- 27249883 TI - The Importance of the Medical Record: A Critical Professional Responsibility. AB - Comprehensive, detailed documentation in the medical record is critical to patient care and to a physician when allegations of negligence arise. Physicians, therefore, would be prudent to have a clear understanding of this documentation. It is important to understand who is responsible for documentation, what is important to document, when to document, and how to document. Additionally, it should be understood who owns the medical record, the significance of the transition to the electronic medical record, problems and pitfalls when using the electronic medical record, and how the Health Information Technology for Economic and Clinical Health Act affects healthcare providers and health information technology. PMID- 27249884 TI - Hard Internet Truths: 34,748 Online Reviews Reveal What Patients Really Want from Doctors. AB - For all of us living in the Internet age, it's hard to underestimate the power of online reviews. Before booking a reservation at a new hotel or restaurant, who doesn't consult websites such as TripAdvisor and Open Table? Who would gamble $100 on a dinner out or $200 on a hotel stay before first seeing what other diners and patrons had to say about their experiences? Patients who are looking for a healthcare provider are no different than those customers looking for a restaurant or a hotel; they want opinions from others who have previously availed themselves of that restaurant or hotel. This article addresses the importance of online reputation management and offers ideas and suggestions for healthcare providers to control and protect their online reputations. PMID- 27249885 TI - Practice Consolidation: Forces Not of Nature, but of Government, Demographics, Economics, and Technology. AB - The demand for healthcare services is increasing more rapidly than the supply of providers, while reimbursement levels ignore the free market law of supply and demand. The regulated healthcare environment in the United States fails to increase prices (i.e., reimbursement rates) as demand outstrips supply. Healthcare practitioners must find alternative methods in order to continue providing excellent patient care while at the same time maintaining an economically viable practice. Practice consolidation with the assistance of private equity healthcare investment is an extremely attractive solution to this imbalance. PMID- 27249886 TI - Compounded Medications and Physicians' Q&A on Current Legal Issues. PMID- 27249887 TI - Taking in a Show. AB - Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments. PMID- 27249888 TI - Ten Most Commonly Asked Questions About Closing a Consult. PMID- 27249889 TI - Comparison of Endometrial Pathology between Tissues Obtained from Manual Vacuum Aspiration and Sharp Metal Curettage in Women with Abnormal Uterine Bleeding. AB - OBJECTIVE: To study the correlation of endometrial pathology, which were derived from manual vacuum aspiration (MVA) and sharp metal curettage (SMC). MATERIAL AND METHOD: Women aged over 35 years old who presented with abnormal uterine bleeding were enrolled. Endometrial biopsy using MVA and sharp metal curettage under paracervical nerve block were performed, respectively. Correlation of endometrial pathology from both methods and correlation between endometrial pathology from MVA and the most severe pathology were analyzed using Kappa statistics. RESULTS: One hundred and thirty two women were enrolled Nine cases were drop out because of inability to pass the MVA's cannula through the cervical os. Mean age was 49.3 +/- 8.5 years old. Mean BMI was 25.1 +/- 4 kg/m2. Pathological correspondence between tissue obtained from MVA and sharp metal curette was 64.2% and the Kappa agreement was 0.56 (K0 = 0.56, p-value < 0.05). Pathological correspondence between tissue obtained from MVA and the most severe pathology was 92.7% and the Kappa.agreement was 0.86 (K = 0.86, p-value < 0.05). MVA could diagnose all cases of malignancy and endometrial hyperplasia. CONCLUSION: Manual vacuum aspiration (MVA) can be used as an alternative diagnostic procedure in women with abnormal uterine bleeding. PMID- 27249890 TI - Performance of Chemiluminescent Microparticle Immunoassay in Screening for Syphilis in Pregnant Women from Low-Prevalence, Resource-Limited Setting. AB - OBJECTIVE: This study evaluated the diagnostic performance of chemiluminescent microparticle immunoassay (CMIA) in screening for syphilis in Asian pregnant women. MATERIAL AND METHOD: This study retrospectively reviewed the CMA results of pregnant women attending the antenatal care clinic, King Chulalongkorn Memorial Hospital. Women with reactive CMA results were extracted from the laboratory database and further analyzed. A reactive/positive result for Treponema pallidum was defined as having a sample/cut-off absorbance ratio of >= 1.0. Samples were also tested by rapid plasma reagin (RPR) and Treponema pallidum particle agglutination assay (TPPA). RESULTS: From February 2011 to January 2013, a total of 11,640 pregnant women were tested and 65 women (0.56%) had reactive CMIA results. Among these cases, 58 women (89.2%) had non-reactive RPR results. TPPA were non-reactive in 35 women (60.3%) who had non-reactive RPR results. A total of 23 women (39.7%) with RPR non-reactive and TPPA reactive results; therefore, the prevalence rate of syphilis in this population was estimated as 1.98 per 1,000 pregnant women. Among this, 7 cases had a history of past, partial treatment for syphilis and 16 cases were considered as untreated, late, latent syphilis. If RPR tests were used as the screening test, 16/23 cases (69.6%) cases with untreated syphilis would be missed. CONCLUSION: Even though CMIA has high false positive results, however it is still recommended that this reverse sequence screening be used instead of the traditional algorithm. The rate of false positive results can be decreased by adjusting the sample/cut-off absorbance ratio of CMIA. PMID- 27249891 TI - A Participatory Randomized Controlled Trial in Knowledge Translation (KT) to Promote the Adoption of Self-Monitoring of Blood Glucose for Type 2 Diabetes Mellitus Patients in An Urban District of Thailand. AB - OBJECTIVE: To examine effectiveness of self-monitoring of blood glucose (SMBG) in glycemic control for poor control diabetes patients, and test whether the glycemic outcome for those with the 7-point SMBG was better than those with 5 point SMBG or usual care. MATERIAL AND METHOD: Randomized-controlled trial (RCT) of patients with type 2 diabetes mellitus aged 30 years or older HbA1c > 7. Patients were randomly allocated to one of three groups; 7-point SMBG 5-point SBMG and control group. Differences in HbA1c at 6 months and baseline were compared among groups. RESULTS: A total of 191 patients with poor control of diabetes were included. Compared with baseline, at 6 months, average change in HbAlc among control, 7-point, and 5-point SMBG were -0.38, -0.87, and -0.99 (p = 0.04), respectively. The corresponding percentages of patients with reduced HbA1c were 57.1%, 77.6% and 75.5%, respectively (p = 0.03). Using different cut-off values for HbA1c (< 7 and < 7.5) resulted in different percentage distribution of T2DM patients among the 3 groups, yet the differences were not statistically significant. Reductions in body weight were observed in both SMBG groups but not in the control group. CONCLUSION: Using RCT on participatory basis, SMBG with individual dietary counseling was effective in short term. Further engagement with the provider team, the patients/care takers and the health care financing agency to integrate SMBG in the care protocol for poor control diabetes should be considered. PMID- 27249892 TI - Effect of Anti-Hypertensive Medication Withdrawal in Well-Controlled Treated Hypertensive Patients: Preliminary Results. AB - OBJECTIVE: To determine prevalence of hypertensive (HT) patients whose BP can be normalized (hospital BP < 140/90 mmHg) for at least a year and still remained normotensive (NT) after 12-week anti-HT drug withdrawal. Clinical characteristics of this group of patients were assessed. MATERIAL AND METHOD: At least a year of well controlled HT patients by hospital BP without target organ damage and diabetes mellitus who were treated with single low-to-standard dose anti-HT medication in hypertension clinic, Siriraj Hospital were screened. After an informed consent was signed, epidemiologic data, cardiovascular risks and laboratory data done within a year was collected. The anti-HT drug taken would be discontinued and a series of home blood pressure (HBP) was measured twice a day (wake-up time and bed time) for 2 weeks. The anti-HT drug was still discontinued in normal HBP group (average HBP < 135/85 mmHg) and reassessed hospital BP 10 weeks later (week 12). Previous anti-HT medications were resumed in high HBP group (average HBP >135/85 mmHg), at week 2. At week 12, those who became hypertensive (hospital BP > 140/90 mmHg) would be advised to continue the drug. RESULTS: Ninety-five patients were recruited. Six patients were excluded since they did not complete HBP measurement data. After 2 weeks of antihypertensive drug discontinuation, 16 out of 89 patients enrolled were found to be HT by HBP. The rest 73 patients (82.0%) were remained NT At week 12, 7 patients (7.9%) self administrated drug prior to the visit date. Therefore, 66 patients (74.1%) were left for further analyses. Of them, 55 patients (61.8%) were still NT by hospital BP and 11 patients (12.3%) turned to be HT. There were no significant differences of all risk factors studied between those NT and HT, except male was found in a higher proportion than female (p = 0.021). CONCLUSION: Fifty five patients (61.8%) out of 89 enrolled patients are still NT and able to stop anti-HT drug after 12 weeks follow-up. Male had a higher rate to remain NT than female. PMID- 27249893 TI - A Comparative Study of 3 Different Methods of Temperature Measurement in Children. AB - BACKGROUND: The accuracy of body temperature measurement is very important in children. The accuracy and reliability of the forehead skin thermometer (FST) and infrared tympanic thermometer (TT) are inconclusive. OBJECTIVES: To determine: 1) the mean difference, agreement, and accuracy of body temperature detected in children by FST and ITT, as compared with the gold standard rectal mercury-in glass thermometer (RMT); and, 2) the cut-off level for FST and ITT in the detection of fever MATERIAL AND METHOD: Children <= 2 years old with the chief complaint of "fever" were recruited for this study. Body temperature (BT) was measured by 3 different methods, including FST 5 times; ITT 3 times; and, RMT, 1 time, for each patient. Each measurement method was performed by 3 well-trained staff members, all of whom were blinded to the recorded data of the other methods. The mean difference in body temperature, agreement by Bland-Altman method, and the verified performance of FST and ITT by diagnostic test were assessed. RESULTS: A total 312 children were recruited. Body temperatures measured by FST and ITT were lower than those measured by RMT, with a mean difference of 1.04 degrees C (p < 0.001) and 1.03 degrees C (p < 0.001), respectively. In subgroup analysis by levels of fever the mean differences between rectal temperature and both forehead and ear temperature were statistically significantly different (p < 0.001) for all levels of fever. Regarding the diagnostic test to verify performance, the data revealed the most practical cut-off point to be 37.0 degrees C for both FST and ITT as compared to the gold standard RMT. CONCLUSION: Both FST and ITT were found to be accurate temperature screening methods for daily clinical use. However, the cut-off points to detect fever should be lowered to 37.0 degrees C to be consistent with gold standard measurement. PMID- 27249895 TI - Effectiveness of Medium Chain Triglyceride Ketogenic Diet in Thai Children with Intractable Epilepsy. AB - OBJECTIVE: To determine the efficacy, side effects and feasibility of Medium chain triglyceride (MCT) ketogenic diet (KD) in Thai children with intractable epilepsy. MATERIAL AND METHOD: Children with intractable epilepsy were recruited. Baseline seizure frequency was recorded over 4 weeks before starting MCT KD. Average seizure frequency was assessed at 1 month and 3 months, compared to the baseline using Wilcoxon Signed Rank Test. Side effects and feasibility were also assessed by blood tests and an interview. RESULTS: Sixteen subjects were recruited with mean seizure frequency of 0.35-52.5 per day. After treatment, there was a significant reduction in seizure frequency, ranging from 12% to 100% (p = 0.002 at 1 month, and 0.001 at 3 months). 64.3% of the subjects achieved more than 50% seizure reduction at 3 months and 28.6% of the patients were seizure-free. Common adverse effects were initial weight loss (37.5%) and nausea (25%). 87.5% of subjects and parents were satisfied with the MCT KD with 2 cases dropping-out due to diarrhea and non-compliance. CONCLUSION: MCT ketogenic diet is effective and feasible in Thai children with intractable epilepsy. Despite modification against Asian culinary culture, the tolerability and maintenance rate was still satisfactory. A larger study is required. PMID- 27249894 TI - Clinical Features and Survival Outcomes of Invasive Aspergillosis in Pediatric Patients at a Medical School in Thailand. AB - BACKGROUND: Invasive aspergillosis (IA) is a severe infection in immunocompromised patients. Recently, serum galactomannan has been widely used for diagnosis and voriconazole as an antifungal agent. The objective of this study is to describe clinical features and survival outcomes of IA. MATERIAL AND METHOD: A retrospective chart review of IA in patients younger than 18 years old at King Chulalongkorn Memorial Hospital, Thailand, was conducted. Clinical definitions were based on criteria oft he European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) 2008. RESULTS: Between January 2006 and December 2012, 40 cases of invasive aspergillosis were identified, classified as proven (8 patients, 20%), probable (28, 70%), and possible IA (4, 10%). Median age of patients was 10 years (range, 42 days-17 years). The most common underlying disease was hematologic malignancy (60%). The major risk factor was neutropenia (65%) with median duration of 21 days (range, 4 58 days). The most common site of infection was in the lungs (80%). The most common computed tomography chest finding was nodules (71%). An air crescent sign was seen only in 11% and a halo sign was found only in 7% of patients. Serum galactomannan was positive in 78% of patients with median value of 1.34 (range 0.5-5.6). Only seven patients (17%) had microbiological confirmation, of which were Aspergillus flavus (4 cases) and Aspergillus fumigates (3 cases). Antifungal therapy included voriconazole (23 patients, 58%), amphotericin B (12, 30%), liposomal amphotericin B (3, 8%), caspofungin (1, 2%) and itraconazole (1, 2%). Two deaths related to angioinvasive complications of aspergillosis (pulmonary hemorrhage and rupture mycotic aneurysm) were reported The 3-month and 12- month survival rates after diagnosed IA were 73.7% and 56.7%, respectively. The major cause of death was new episode of sepsis found in 11 cases (52%). CONCLUSION: The 1-year survival rate was poor; however, cause of death is related to complications of the immunocompromised state not from IA. PMID- 27249896 TI - School-Based Educational Interventions Can Significantly Improve Health Outcomes in Children with Asthma. AB - BACKGROUND: Lack of asthma knowledge among the pediatric patients and their caregivers contribute to poor asthma control in children. There is no data from Thailand on the health outcomes of school-based educational interventions for asthmatic children. OBJECTIVE: To assess the effectiveness of school-based asthma educational interventions on health outcomes, asthma control, and management in asthmatic children. MATERIAL AND METHOD: Forty-seven asthmatic students (6-15 years old), 14 caregivers, and five teachers from the Homkred School participated in the study. Asthma knowledge, workshops on pMDI (pressurized metered dose inhaler) techniques, use of asthma diaries, and self-management plans were provided Pre- and post-tests were administered to assess the asthma knowledge of the asthmatic students, their caregivers, and teachers. Pulmonary function tests (PFT) were used to assess the health outcomes. The controls of asthma and self management behaviors were assessed at three and six months post-intervention. RESULTS: There were significant improvements of asthma knowledge in all groups (p < 0.01) immediately post-intervention and six months later. At pre-intervention phase, there were 18 children who had FEV1 less than 80% of the predicted value. Their PFT significantly improved for all parameters at post-intervention, but in children who had normal FEV1 at baseline, there were no significant changes. Control of asthma was significantly better three and six months post intervention. The rate of regular use of ICS (inhaled corticosteroid) significantly increased to 40% at three months and 30% at six months (p < 0.001) post-intervention. In addition, the self-management behaviors in the asthmatic children improved. The teachers' management of asthmatic attacks during the classes also improved. As a result of this, there were fewer emergency room (ER) visits. CONCLUSION: School-based educational interventions can significantly improve asthma outcomes in children with asthma. Therefore, the authors highly recommend the use of this intervention. PMID- 27249897 TI - Seroepidemiology of Dengue Virus Infection in HIV-Infected Children in Comparison to Healthy Children. AB - BACKGROUND: Dengue infection is the most common arboviral infection in the world while the HIV/AIDS epidemic remains a global concern. The pathogenesis of both diseases is rather on the contrary and it is generally observed that dengue diseases are uncommon in children with AIDS. OBJECTIVE: To study the seroprevalence of dengue virus infection in HIV-infected children compared to healthy children. MATERIAL AND METHOD: A cross-sectional seroprevalence of dengue virus was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Eighty-six HIV-infected children aged less than 15 years and one hundred age matched healthy children were enrolled. HIV-infected children were classified in categories by CDC 1994 criteria. Neutralizing antibodies to all four dengue serotypes (DEN1, DEN2, DEN3, and DEN4) were measured by plaque reduction neutralization test (PRNT). RESULTS: Fifty out of 86 (58%) HIV-infected children and 65 out of 100 (65%) healthy, HIV-negative children had positive neutralizing antibody against dengue virus by PRNT There were no significant differences between these two groups (p > 0.05). Most children had neutralizing antibody against DEN2. In HIV-infected children, a monotypic PRNT50 pattern was found in 26 children (30%) and multitypic pattern was found in 24 children (28%). Most children had neutralizing antibody against DEN2. There were no significant differences in dengue seroprevalence between these two groups. CONCLUSION: HIV infected children and healthy children had no different seroepidemiology of dengue virus infection. PMID- 27249898 TI - Wilson's Disease in Thai Children between 2000 and 2012 at King Chulalongkorn Memorial Hospital. AB - OBJECTIVE: Wilson's disease (WD) is a rare autosomal recessive disorder characterized by copper accumulation. Clinical presentations are extraordinarily diverse, and currently no single diagnostic test can confirm WD with high accuracy. A complete understanding of the presentations and improved diagnostic methods are important for disease management. The authors' aimed to examine disease characteristics, management, and treatment outcome of WD in children, especially when genetic analysis and liver copper measurements were limited. MATERIAL AND METHOD: Data was collected from 21 WD children who were treated at King Chulalongkorn Memorial Hospital between 2000 and 2012. Inclusion criteria followed the WD scoring system, where other liver diseases are ruled out systematically. RESULTS: The mean age at diagnosis was 13.5 +/- 3.36 years, with 19 symptomatic patients, and two asymptomatic individuals who were diagnosed through family screening. Presentations varied, jaundice (52%), ascites (52%), edema (52%), Coombs-negative hemolytic anemia (14%), neurological abnormalities (33%), renal involvement (19%), and fulminant hepatic failure (5%). Based on the key parameters in WD scoring system, 14 patients (66%) had Kayser-Fleischer (KF) rings. Seventeen (89%) had low serum ceruloplasmin, and 20 (95%) had increased urinary copper excretion. These positive findings made WD scoring system accurately diagnose 66% of patients. Chelation therapy was the first line of therapy for all patients except one, who underwent liver transplantation. After therapy, liver function test returned to normal in all patients. However, neurological symptoms did not improve with combined drug therapy using chelating and neuropsychiatric agents. CONCLUSION: WD in children mostly affected the liver WD was suspected in seven patients (34%), thus needed further investigation. Therefore, long-term follow-up in those with suspected WD is the appropriate method for diagnosis and management in limited diagnostic tests. We suggest further treatment, and use of clinical response to treatment, as a criterion for confirming the WD diagnosis. PMID- 27249899 TI - Safety of Phenylephrine in Antihypotensive Treatment during Spinal Anesthesia for Cesarean Section. AB - OBJECTIVE: In Thailand, hypotension after spinal anesthesia for cesarean section is routinely treated by ephedrine. As incidence of fetal acidosis reportedly increases resulting from placental transfer of ephedrine, phenylephrine, an alpha 1 agonist with less lipid solubility, becomes an alternative. However, the potential development of serious bradycardia after phenylephrine is a concern. The objectives of this study were to investigate the incidence of serious bradycardia and identify risk factors associated with phenylephrine-induced serious bradycardia and other side effects of phenylephrine. MATERIAL AND METHOD: This descriptive cross-sectional study was conducted between July 1, 2014 and March 15, 2015 on 509 parturients undergoing cesarean section under spinal anesthesia. Predelivery hypotension was treated by intravenous phenylephrine 100 mcg and pretherapeutic heart rate (pHR) was recorded. If serious bradycardia (HR < 60 bpm and hypotension or HR <45 bpm) developed, atropine 0.6 mg was administered intravenously. Data were analyzed using multivariable logistic regression and AuROC. RESULTS: Incidence of serious bradycardia was 11% (95% CI: 8.0-14.0). A one bpm increment increase in pHR reduced this incidence by 4% (adjusted OR: 0.96; 95% CI: 0.94-0.98, p < 0.001; AuROC: 0.76). As compared to apHR greater than 80 bpm, apHR of 61 to 80 bpm and a pHR of 60 bpm or lower increased the risk of serious bradycardia by 3.55 times and 12.81 times, respectively. Other risk factors were height (adjusted OR: 0.94; 95% CI: 0.89 0.98, p = 0.015), baseline DBP (adjusted OR: 0.97; 95% CI: 0.94-0.99,p = 0.03), and anesthetic level at first minute (adjusted OR: 1.13; 95% CI: 1.02-1.23, p = 0.02). Benign and temporary abnormal ECG readings were noted. CONCLUSION: Phenylephrine for antihypotensive treatment in spinal anesthesia induces bradycardia. Findings indicate an association between slower HR at time phenylephrine is administered and serious bradycardia. Close ECG monitoring and prompt treatment are required. PMID- 27249900 TI - Effects of Precooling with Cold Water Ingestion on Thermoregulatory Response of Obese Men during Moderate Intensity Exercise in Hot and Humid Environment. AB - OBJECTIVE: 1) To determine rectal temperature (Tre) and fluid loss (FL) of obese men (OM) compared to non-obese men (NM) during exercise in cool conditions (CC) and hot and humid conditions (HC), and 2) to investigate the effects of cold water (CW; 0.5 +/- 0.5 degrees C) ingestion before exercise in HC in OM MATERIAL AND METHOD: Twelve OM and 12 NM completed 2 treadmill exercise sessions, in CC and HC, in a randomized order Each session was performed for 30 minutes at 45-50% of heart rate reserve with a 5-minute warm up and 5-minute cool down. RESULTS: There were no differences in Tre in response to exercise between OM and NM both in CC (OM 37.77 +/- 0.08 degrees C, NM 37.68 +/- 0.08 degrees C; p = 0.463) and in HC (OM 37.82 +/- 0.06 degrees C, NM 37.85 +/- 0.06 degrees C; p = 0.725). Heart rate, perceived exertion and thermal sensations were not significantly different between OM and NM. However, compared to NM, fluid loss (FL) was approximately 160 mL greater in OM (OM 443.33 +/- 98.65 mL, NM 283.33 +/- 108.15 mL; p <= 0.001) in CC, and was 194 mL greater (OM 632.50 +/- 126.57 mL, NM 438.33 +/- 126.62 mL; p <= 0.001) in HC. In HC, the 12 OM performed additional 2 bouts of exercise, with CW vs. ambient temperature water (AW; 30.5 +/- 0.5 degrees C) ingestions prior to the start of exercise. Precooling with CW ingestion, compared to AW ingestion, showed no significant difference in Tre but CW was able to reduce FL (CW 646.67 +/- 139.82 mL, AW 735 +/- 126.95 mL; p = 0.010). CONCLUSION: OM may continuously exercise about 30 minutes at moderate intensity in HC without the increase of Tre to dangerous levels. However, OM should drink approximately 200 mL more water in HC and 160 mL more water in CC than NM. Precooling with CW ingestion is a good method of reducing risk of exertional heat illnesses in obese individuals during exercise in HC, as it decreases the amount of FL induced by exercise. PMID- 27249901 TI - Estrous Cycle Induces Peripheral Sensitization in Trigeminal Ganglion Neurons: An Animal Model of Menstrual Migraine. AB - BACKGROUND: Many women experience menstrual migraines that develop into recurrent migraine attacks during menstruation. In the human menstrual cycle, the estrogen level fluctuates according to changes in the follicular and luteal phases. The rat estrous cycle is used as an animal model to study the effects of estrogen fluctuation. OBJECTIVE: To investigate whether the estrous cycle is involved in migraine development by comparing the neuronal excitability of trigeminal ganglion (TG) neurons in each stage of the estrous cycle. MATERIAL AND METHOD: Female rats were divided into four experimental groups based on examinations of the cytologies of vaginal smears, and serum analyses of estrogen levels following each stage of the estrous cycle. The rats in each stage of the estrous cycle were anesthetized and their trigeminal ganglia were removed The collections of trigeminal ganglia were cultured for two to three hours, after which whole-cell patch clamp experiments were recorded to estimate the electrophysiological properties of the TG neurons. RESULTS: There were many vaginal epithelial cells and high estrogen levels in the proestrus and estrus stages of the estrous cycle. Electrophysiological studies revealed that the TG neurons in the proestrus and estrus stages exhibited significantly lower thresholds of stimulation, and significant increase in total spikes compared to the TG neurons that were collected in the diestrus stage. CONCLUSION: Our results revealed that high estrogen levels in the proestrus and estrus stages altered the thresholds, rheobases, and total spikes of the TG neurons. High estrogen levels in the estrous cycle induced an increase in neuronal excitability and the peripheral sensitization of TG neurons. These findings may provide an explanation for the correlation of estrogen fluctuations during the menstrual cycle with the pathogenesis of menstrual migraines. PMID- 27249902 TI - Pleiotropic Effects of Simvastatin on Wound Healing in Diabetic Mice. AB - OBJECTIVE: To evaluate the effects of pre-treatment with low-dose simvastatin on angiogenesis and wound healing in a diabetic mouse model. MATERIAL AND METHODS: Balb/c nude mice were divided into three groups, including control (CON), diabetic (DM, and diabetic pre-treated with low-dose simvastatin (DM+ SIM). Seven days prior to wounding, the DM + SIM group was started on oral simvastatin (0.25 mg/kg/day). Eleven weeks after diabetes was induced, all mice were subjected to a bilateral full-thickness excisional skin wound on the back (0.6 x 0.6 cm2). On day 14 after wounding, percentage of wound closure (%WC), percentage of capillary vascularity (%CV), and neutrophil infiltration were determined using Image Pro Plus, confocal fluorescence microscopy, and hematoxylin and eosin (H&E) staining, respectively. Tissue vascular endothelial growth factor (VEGF) was detected by ELISA at days 7 and 14, post-wounding. RESULTS: On day 14, %WC and %CV in CON and DM + SIM groups were significantly increased, with no significant change observed in the DM group. Neutrophil infiltration in the CON and DM + SIM groups was signficantly lower than that of the DM group. VEGF levels in the CON and DM + SIM groups were significantly higher than levels in the DM group on day 7, but not different among groups on day 14. CONCLUSION: The present study demonstrated that pre-treatment with low-dose simvastatin could increase angiogenesis, reduce inflammation, and improve wound healing in diabetic mice. PMID- 27249903 TI - Radiation Exposure to Relatives of Patients Treated with Iodine-131 for Thyroid Cancer at Siriraj Hospital. AB - OBJECTIVE: Thyroid cancer patients treated with 1-131 are potential source of radiation exposure to relatives who are knowingly and willingly exposed to ionizing radiation as a result of providing comfort to patients undergoing I-131 therapy. This study aims to determine radiation dose received by relatives who care for non self-supporting 1-131 patients at Siriraj Hospital. MATERIAL AND METHOD: Twenty caregivers of 20 patients underwent I-131 therapy for thyroid cancer with a standard protocol were given specific instructions with regard to radiation safety and provided with electronic digital dosimeter to continuously measure radiation dose received on daily basis, three days in the hospital. On the day patient is released, thyroid uptake estimates were performed to assess internal radiation dose received by caregivers. RESULTS: The 3-day accumulative doses to caregivers to patients receiving 150 mCi (n = 11) and 200 mCi (n = 9) of I-131 ranged from 37 to 333 uSv and 176 to 1,920 pSv respectively depending on the level of supports required. Thyroid uptake estimates in all caregivers were undetectable. Dosimeter indicated a maximum whole-body dose of1.92 mSv was more than the public dose limit of] mSv but within the dose constraint of 5 mSv for caregivers. DISCUSSION: Radiation dose to caregivers of a non self-supporting hospitalized patient undergoing 1-131 therapy were well below the limits recommended by the ICRP. The patients can be comforted with confidence that dose to caregivers will be less than the limit. CONCLUSION: This study provides guidance for medical practitioners to obtain practical radiation safety concerns associated with hospitalized patients receiving I-131 therapy especially when patient needs assistance. PMID- 27249904 TI - Total Effective Dose Equivalent to Caregivers from Hospitalized Patients Treated with High Dose Radioiodine for Thyroid Carcinoma. AB - Thyroid cancer patients treated with high-dose radioactive iodine (3.7-7.4 GBq) are different from other people because after the administration, the radionuclide I-131 is excreted via urine, feces, saliva and breathing, and also via exposure to other patients. Caregivers of the patient may receive higher radiation doses than normal. The purposes of this study were to estimate the total effective dose equivalent from internal and external exposure to caregivers of patients treated with high dose I-131 admitted at Siriraj Hospital, and to compare the estimated dose with the dose constraint of 5 mSv per annum for caregivers. Thirteen caregivers of 13 patients who underwent radioiodine therapy for thyroid cancers following a standard protocol were given specific instructions with regard to radiation safety and were attached to an electronic personal dosimeter and a personal air sampler pump continuously to measure received radiation dose on a daily basis over three days in the hospital. On discharge day, caregivers were asked to perform an in vivo bioassay by the thyroid uptake instrument. The results from the thirteen caregivers were divided into 3 groups. The total effective dose equivalent to caregivers of patients administered 3.7 GBq (n = 1), 5.55 GBq (n = 9), and 7.4 GBq (n = 3) were 0.159 mSv, 0.123 to 0.629 mSv, and 0.631 to 0.718 mSv, respectively. There values were well below 5 mSv per episode as proposed in the IAEA Safety Reports Series No. 63 and the ICRP Publication 103. PMID- 27249905 TI - Development of a Food Insecurity Screening Instrument. AB - BACKGROUND: Food insecurity is a dynamic, global issue requiring our constant attention today, and practical assessment instruments are needed to detect food insecurity in various populations and countries. A screening tool for food insecurity was developed and tested its psychometric properties. MATERIAL AND METHOD: The Food Insecurity Screening Instrument (FISI) was developed based on literature review and qualitative data from a sample of 30 female who were family food providers in crowded urban communities in Bangkok. RESULTS: Content validity was determined by five experts, resulting in a good content validity index. It was tested with another 350 food providers, resulting in high reliability Item analysis revealed good internal consistency of items to total scale, except for two items which were deleted. Construct validity was determined using exploratoiy factor analysis, and revealed four factors, consisting of 33 items, food quantity, food quality, food safety, and anxiety about food These factors together explained 74.9% of total variance of the new tool. CONCLUSION: This new tool provides a valid and reliable means of screening for food insecurity in families and communities. Policy makers in Thailand have supported the usefulness of the instrument which has already been used across the country for the National Survey, and after the 2011 Thai floods. PMID- 27249906 TI - Residents' Obstacles and Attitudes Toward Research during Residency Training. AB - BACKGROUND: Many residents often encounter several problems to accomplish their research projects, a requirement to complete medical residency training in Thailand. This study aimed to explore perceived obstacles and attitude of Thai residents toward conducting research. MATERIAL AND METHOD: The questionnaires were distributed among 640 residents at King Chulalongkorn Memorial Hospital from November to December 2014. Structured-questionnaires explored the participants' characteristics, research experience, purpose of conducting research, motivations and perceived barriers to research. Five-pointed Likert scale was used to determine residents' attitude toward research. Descriptive statistical analysis was used. RESULTS: 246 respondents were achieved from 640 residents surveyed, yielding a response rate of 39.7%. The mean age was 28.21 +/- 1.60 years and 66.7% was female. Most of them were studying in internal medicine, pediatrics and anesthesiology. Residency year ranged from 1st-4th year and the ratio was 21.5: 20.8:18:1. The purposes to conduct the research were to meet the program requirement (72.4%), to develop research skills (23.6%), and to accrue credentials for future fellowship application (2.4%). While 52.4% pursued research in order to bolster research experience, 12.6% would like to publish and 4.5% would like to present in the international conference, as high as 39.8% had not motivation. Perceived barriers were limited statistical knowledge, inadequate time and, difficulty formulating research topic. In addition, 50.6% were assigned research topics from advisors. Most of the residents agreed that conducting research enhanced inquiry-based learning and enabled them to better understand research methodology. Nevertheless, they thought that researching was complicated, time-consuming, and tedious. CONCLUSION: Most residents were motivated to conduct research projects but perceived obstacles and negative attitude might erode their motivation for research. PMID- 27249908 TI - Diversifying Diversity. AB - A hospital board needs to mirror the people and communities it serves. Progress is being made on board diversity, and there are an increasing number of resources to aid the effort. PMID- 27249907 TI - Listeriosis: Is It a Rare Disease in Thailand? AB - The prevalence of Listeria monocytogenes infection has been characterized as rare in Thailand. Within one month, 3 cases of listeriosis were seen at Vachira Phuket Hospital in Phuket, Thailand. Two cases were neonates with septicemia, of which one made an uneventful recovery and the other expired. The third case was an eleven-year-old boy with meningitis who also succumbed to his illness. All isolated L. monocytogenes were sensitive to ampicillin. An outbreak investigation revealed no L. monocytogenes contamination in tested food sources in Phuket. PMID- 27249909 TI - HEALTH CARE'S POWERFUL NEW TOOL. AB - Predictive analytics can help hospitals and health networks promote wellness, improve patient care, become more efficient and reduce costs. Here's whatyou need to know. PMID- 27249910 TI - At Mass General, 'Serving the Community Is in Our DNA'. AB - This year's winner, Massachusetts General Hospital, is dedicated to addressing the social and economic determinants of health in all of the communities it serves. PMID- 27249911 TI - Rewriting the Script. AB - Pharmacists are coming out from behind the scenes to play a more direct role in patient care, advising on medications both before and after discharge. PMID- 27249912 TI - Innovation: A Playbook That Lets Boards, Leaders Achieve Health System Success. AB - This month's Trustee Workbook outlines four key steps that enable board members and executives to embrace innovation and achieve health systen success. PMID- 27249913 TI - The New Consumer. AB - Pocketbook issues are driving patients to behave like consumers and the health care field to become more like the retail industry. What are the implications for your organization? PMID- 27249914 TI - Grooming M.D. Leaders. AB - CEOs need to target and develop physicians to play leading roles in the transformation of health care--and of their organizations. PMID- 27249915 TI - [APPROACH TO ESTABLISHMENT OF INDICATIONS FOR PROGRAMMED SANATION OF ABDOMINAL CAVITY IN DIFFUSE PERITONITIS]. AB - The results of treatment of 33 patients, suffering diffuse peritonitis, with postoperatively applied tactics of the programmed surgical sanation of abdominal cavity were analyzed. Indications for relaparotomy were established, based on the estimation scale for the enteral insufficiency severity. The patients death and the complications causes were analyzed, depending on terms and rates of relaparotomy conduction. PMID- 27249916 TI - [PROGNOSTIC SIGNIFICANCE OF METASTATIC AFFECTION OF REGIONAL LYMPHATIC NODES AND LEVEL OF A LYMPH NODE DISSECTION IN SURGICAL TREATMENT OF GASTRIC CANCER]. AB - In 142 patients, operated on for resectable gastric cancer, a dependence of the survival indices from clinico-morphological characteristics of tumoral process and peculiarities of surgical interventions was studied. Efficacy of a lymph node dissection (LND) on a D1 -D2 level was investigated. There was established, that regional lymph nodes affection in gastric carcinoma causes deterioration of indices of general and disease-free survival. In patients without regional metastases the operation conduction with LND D1 have promoted improvement of indices of general and a disease-free survival, and expansion of a LND up to the D2 level did not guarantee the treatment results improvement. PMID- 27249918 TI - [MORPHOLOGIC CHANGES OF INTRA- AND EXTRAPANCREATIC ARTERIES IN ELDERLY AND SENILE PATIENTS IN ACUTE NECROTIC PANCREATITIS]. AB - In 38 elderly and senile patients, in whom an acute necrotic pancreatitis (ANP) was diagnosed, morphological changes in the walls of intra- and extrapancreatic arteries were studied, including dorsal pancreatic artery, big pancreatic artery (Heller) and their branches. The patients were operated, using open surgical access, on the 10 - 26-th day after admittance to hospital for purulent-septic complications of pancreonecrosis. In total 9 (24%) patients died. Changes of intra- and extrapancreatic arteries causes the essential reduction of the splanchnic blood flow intensity and necrotic changes in pancreatic parenchyma and parapancreatic cellular space. PMID- 27249917 TI - [IMPACT OF QUERCETIN ON SYSTEMIC AND SPLANCHNIC BLOOD CIRCULATION IN A COMPLEX OF PREOPERATIVE PREPARATION IN PATIENTS, SUFFERING AN ACUTE PANCREATITIS]. AB - The results of prospective investigation of 76 patients, suffering an acute pancreatitis, in whom Quercetin was applied in content of a starting liquid resuscitation in complex of preoperative preparation, were studied. Its impact on the indices of systemic and splanchnic blood circulation, as well as results of an acute pancreatitis treatment was studied. Inclusion of Quercetin into a scheme of the patients preoperative preparation have promoted the improvement of indices of systemic hemodynamics and the cardiac pump function and enhancement of the left ventricle mechanical work by 18.4% (p < 0.01) at average. A trustworthy reduction of the peak systolic velocity of blood flow in the splanchnic space vessels was established. The systemic and regional blood circulation improvement caused a reduction of the organ dysfunction rate, as well as polyorgan insufficiency from 71.4 to 28.6%. PMID- 27249920 TI - [PROPHYLAXIS OF INFILTRATIVE-INFLAMMATORY COMPLICATIONS OF THE WOUNDS HEALING IN PATIENTS, OPERATED ON FOR NONCOMPLICATED HERNIA OF ANTERIOR ABDOMINAL WALL]. AB - The results of investigation of the inflammatory processes dynamics in operative wounds in 238 patients after surgical intervention, performed for noncomplicated hernias of anterior abdominal wall of various localization, as well as the impact of polarized light on correction of the vegetative nervous system disorders, for prophylaxis of infiltrative-purulent complications were analyzed. PMID- 27249919 TI - [APPLICATION OF PRESEPSIN IN DIAGNOSIS AND TREATMENT OF PURULENT-SEPTIC COMPLICATIONS OF ACUTE NECROTIC PANCREATITIS]. AB - In 70 patients, suffering an acute necrotic pancreatitis (ANP), and 10 practically healthy persons a content of presepsin in a blood plasm, using immunochemiluminescent method and conducted bacteriological investigations, were analyzed. The infection occurrence is accompanied by plausible upgrading of a presepsin level in a blood plasm, depending on activity and severity of a septic process: in local infection--up to (677 +/- 30) pg/ml, sepsis--up to (988 +/- 47) pg/ml, severe sepsis--up to 2668 pg/ml; in an ANP without infection it have constituted (332 +/- 38) pg/mI at average, in practically healthy persons--(184 +/- 16) pg/mI. A presepsin level correlates with a state severity in accordance to APACHE I scale, what permits to estimate the patients state severity objectively, to prognosticate a favorable and unfavorable consequences of treatment, rapidly changing, depending on efficacy of treatment. PMID- 27249921 TI - [RECONSTRUCTIVE-RESTORATION OPERATIONS AFTER OBSTRUCTIVE RESECTION OF LARGE BOWEL]. AB - The results of reconstructive-restoration operations, performed after obstructive resection of large bowel for colorectal cancer, were analyzed. The postoperative complications rate have constituted 11.7%. The most frequent cause of morbidity, 3.9%, was partial insufficiency of sutures of interintestinal anastomosis, formatted in the end to end fashion. Lethality have constituted 1.1%. PMID- 27249922 TI - [SURGICAL TREATMENT OF FOCAL HEPATIC AFFECTION: ANALYSIS OF THE RESULTS AND PERSPECTIVES]. AB - Basing on own material analysis (386 observations) and the literature date there was established, that hepatic resection occupies the first place in treatment of the organ focal affection, together--nontumoral and a tumoral one. The treatment of all kinds of focal hepatic affection must be expanded in a specialized clinic in the Ukraine. The main task of the investigation was to determine a permissible volume of hepatic resection, depending on functional state of the organ parenchyma, improvement of existing and elaboration of a new methods of operative intervention, directed on the complications prophylaxis and the hepatic function preservation. PMID- 27249923 TI - [APPLICATION OF MINIINVASIVE INTERVENTIONS UNDER ULTRASONOGRAPHIC CONTROL FOR NONPARASITIC HEPATIC CYSTS]. AB - The results of treatment of 21 patients, suffering nonparasitic hepatic cysts, using laparoscopic draining and puncture under ultrasonographic control, were analyzed. Minimal traumaticity of the intervention, absence of necessity to apply general anesthesia, low rate of postoperative morbidity (7.1%), reduction of duration of the patients stationary treatment down to (3.3 +/- 0.61) days, reduction of economic wastes on the treatment constitute the advantages of such method. PMID- 27249924 TI - [SURGICAL TREATMENT OF ACUTE CHOLANGITIS IN CHOLEDOCHOLITHIASIS]. AB - The results of surgical treatment of 184 patients for obstructive jaundice and an acute cholangitis in choledocholithiasis were analyzed. Acute cholangitis was diagnosed in 62 (33.7%) patients. Sensitivity of a Tokyo Guidelines (2013)--TG 13 criteria for diagnosis and estimation of the course severity of an acute cholangitis was studied. Dynamics of postoperative laboratory parameters was studied. There was established, that occurrence of obturation jaundice and cholangitis coincides with pronounced hepatic function disorders, which are preserved after a bile outflow restoration also, and changes in peripheral blood. Severity of inflammatory reaction reflects hematological indices, the most informative of which is an intoxication index. PMID- 27249925 TI - [HEMOSTASIOLOGIC INDICES AFTER LAPAROSCOPIC CHOLECYSTECTOMY FOR AN ACUTE CHOLECYSTITIS]. AB - The indices of coagulometry and thromboelastography (THEG) were determined in 60 patients, suffering various forms of an acute cholecystitis. Preoperatively the coagulometry indices have had a hypercoagulation tendency while the disease severity enhances. After performance of laparoscopic cholecystectomy the most essential changes of indices were observed. In the patients after severe operation there was observed accelerated kinetics of the blood clotting, witnessed by the THEG indices. The risk of the hemorrhage occurrence restricts application of medicinal thromboprophylaxis. PMID- 27249926 TI - [FUNCTIONAL STATE OF PERIPHERAL VESSELS OF THE LOWER EXTREMITIES AND INTRAOSSEOUS PRESSURE IN PATIENTS, SUFFERING OBLITERATING ATHEROSCLEROSIS ON BACKGROUND OF DIABETES MELLITUS]. AB - Results of examination of 46 patients, suffering obliterating atherosclerosis of the lower extremities arteries solely or in combination with diabetes mellitus (DM), were analyzed. The malleolar pressure index (MPI), regional systolic pressure (RSP), velocity of the volume blood flow (VVBF), rheographic index (RI), using test with nitroglycerine, postocclusion venous pressure (POVP) and intaosseous pressure (IOP) in tibiae were studied. The RI reduction, parallel to the arterial ischemia progression, was established. The test indices with nitroglycerine in patients with obliterating atherosclerosis have reduced step by step. With coexistent DM the efficacy of nitroglycerine was practically absent. POVP is upgraded in patients of all the groups and it have lowered step by step in a laying position of the patient, and while transition into standing position- it have upgraded progressively with a progress of arterial ischemia. IOP have upgraded significantly in isolated obliterating atherosclerosis in ischemia stage 3a and have lowered--in stage 3b. In coexistent DM IOP is upgraded in ischemia stage 3b also. PMID- 27249927 TI - [THE RISK OF OCCURRENCE OF THE VARICOSE DISEASE RECURRENCE, DEPENDING ON DIAMETER OF VARICOSE--CHANGED VEINS OF LOWER EXTREMITIES WHILE PERFORMANCE OF THE FOAM SCLEROTHERAPY]. AB - The results of treatment of 139 patients, to whom for the varicose disease of lower extremities there was conducted a foam sclerotherapy of trunks and tributaries of big subcutaneous vein, small subcutaneous vein and/or nonsaphenous veins with signs of a valvular insufficiency under ultrasonographic control were presented. Complex of measures for prophylaxis of the disease recurrences and complications was elaborated. PMID- 27249928 TI - [THE TREATMENT OF INJURED PERSONS WITH COMPLICATED PENETRATING THORACIC WOUNDINGS ON TERTIARY LEVEL OF THE MEDICAL CARE DELIVERY]. AB - The results of examination and treatment of 36 injured persons with complicated penetrating thoracic woundings in tertiary centres were analyzed. Own experience of the pulmonary woundings surgical treatment, using application of videothoracoscopic and welding-coagulating equipment, was summarized. PMID- 27249929 TI - [PECULIARITES OF SIMULTANT INTERVENTIONS FOR SOME TYPES OF CHRONIC PHTHISIC PLEURITIS, COEXISTENT WITH PULMONARY TUBERCULOSIS]. AB - In coincidence of chronic phthisic pleuritis in a rigid stage with pulmonary tuberculosis operative intervention is indicated of a pleuropulmonectomy type, what is a complex situation for performance and preservation of the patient's functional state. Pleuropulmonectomy in some patients is complicated by empyema and pathological processes in bronchi. Possibilities of operative interventions application, alternative to pleuropulmonectomy, were studied. Of 48 patients, to whom pleuropulmonectomy is indicated in accordance to data of clinic roentgenological investigations, in 7--simultant operative treatment were conducted with positive results. PMID- 27249930 TI - [CHANGES OF HISTOSTRUCTURE OF CHRONIC ANAL FISSURE, DEPENDING ON DURATION OF THE DISEASE]. AB - The results of histological investigation of the chronic anal fissure (AF) edges in 95 patients with the disease duration from 6 mo to 4.5 yrs were analyzed. Basing on estimation of severity of an acute inflammation signs and the granulation and cicatricial tissue presence there was established, that duration of an acute inflammation in the AF may constitute up to 6 - 7 mo; subacute--from 8 to 11 mo, chronic cicatricial process was observed in terms from 12 mo and more. PMID- 27249931 TI - [INTRAVENOUS INJECTION OF IMMUNOGLOBULINS IN CHILDREN, SUFFERING SEPSIS]. AB - The efficacy of normal immunoglobulin of a man (NIM) injection in children, suffering sepsis and being in extremely severe state, was studied. Of 174 patients, who were treated for sepsis in 2005 - 2014 yrs., in 69 (39.6%)--NIM was applied, in 105 (60.3%)--did not apply. Positive changes of cellular immunity while immunotherapy application were noted. To estimate the immunotherapy efficacy it is mandatory to continue investigations with recruiting more quantity of patients. PMID- 27249932 TI - [THE CHOICE OF THE ANESTHESY OPTIMAL METHOD, USING DETERMINATION OF THE TOLL-LIKE RECEPTORS LEVEL IN THE PLASM AS A MARKER OF HYPERALGESIA IN EARLY POSTOPERATIVE PERIOD]. AB - There were examined 47 children, operated on for tumors of abdominal cavity and retroperitoneal space. The opioid-induced hyperalgesia may occur in early postoperative period. The anesthesia conduction of m. transverses abdominis (TAP block), using 0.375% bupivacaine solution and combined spinal epidural analgesia (CSEA) for postoperative anesthesia have promoted the hyperalgesia severity reduction. Hyperalgesia in early postoperative period was demonstrated by upgrading of the toll-like receptors (TLR-4) level in the blood. The TLR-4 expression increased in the blood was noted while application of a TAP-block and CSEA. PMID- 27249933 TI - [FORMATION OF BILIODIGESTIVE AND INTERINTESTINAL ANASTOMOSES IN ENVIRONMENT OF BILIARY PERITONITIS, USING A HIGH FREQUENCY ELECTRIC WELDING IN EXPERIMENT]. AB - In experiment on 20 rabbits a diffuse biliary peritonitis was simulated, using intraabdominal injection of a laboratory culture of E. coli suspension and a medicinal bile. In 24 h on background of peritonitis on excluded loop of a small bowel in accordance to method of Roux, using a high frequency electric welding with the help of apparatus Patonmed EKB3-300 a one-layered everting cholecystoenteroanastomosis and enteroenteroanastomosis was formated. In a 6 mo postoperatively a connection line was not revealed from outside or from inside, the signs of stenosis were absent. In environment of a diffuse biliary peritonitis a welding technologies have permitted to form a hermetic and competent biliodigestive and interintestinal anastomoses, the processes of a welding suture regeneration postoperatively have a typical course. Using a high frequency-electric welding it is possible to perform a one-staged reconstructive interventions in environment of a pronounced inflammation of tissues due to subsequent precise conjunction of mucosal sheets of connected organs, preventing the anastomotic stricture formation. PMID- 27249934 TI - [MODERN ENDOVASCULAR TREATMENT OF CHRONIC VENOUS DISEASES: THERMAL AND NONTHERMAL PROCEDURES]. PMID- 27249935 TI - [STRATEGY OF ANTIBACTERIAL THERAPY IN PATIENTS WITH SEPSIS. Part 2]. PMID- 27249936 TI - [ACHIEVEMENTS AND UNSOLVED ISSUES OF TREATMENT OF PLEURAL EMPYEMA]. PMID- 27249937 TI - The Critical Role Of VP1 In Forming The Necessary Cavities For Receptor-mediated Entry Of FMDV To The Host Cell. AB - The antigenic inconsistency of the foot-and-mouth disease virus (FMDV) is very broad, such that a vaccine made from one isolate will not offer protection against infection with other isolates from the same serotype. Viral particles (VPs) or surface exposed capsid proteins, VP1-VP3, of FMDV determine both the antigenicity of the virus and its receptor-mediated entry into the host cell. Therefore, modifications of these structural proteins may alter the properties of the virus. Here we show putative cavities on the FMDV-SAT1 (FMDV Southern African Territories1) capsid as possible binding sites for the receptor-mediated viral entry into the host cell. We identified three possible cavities on the FMDV capsid surface, from which the largest one (C2) is shaped in the contact regions of VP1-VP3. Our results demonstrate the significance of VP1, in the formation of FMDV-SAT1 surface cavities, which is the main component in all the identified cavities. Our findings can have profound implications in the protein engineering of FMDV in the contact region of VP1-VP3 found to be embedded in several cavities. Such information is of great significance in the context of vaccine design, as it provides the ground for future improvement of synthetic vaccines to control FMD caused by FMDV-SAT1 serotypes. PMID- 27249938 TI - Structural equation modeling of the quality of life for patients with marfan syndrome. AB - BACKGROUND: We used structural equation modeling to evaluate the quality of life (QOL) for patients with Marfan syndrome (MFS). The goal was to provide guidelines to facilitate the development of interventions and strategies to improve the QOL for patients with MFS. METHODS: The participants fulfilled the Ghent 2 criteria for MFS and they comprised patients who visited the cardiology outpatient department of a tertiary hospital in Seoul, Korea, between August 17, 2013 and April 17, 2014. Demographic, social support, disease-related factors, biobehavioral factors, and QOL data were collected in one-on-one interviews. RESULTS: The final analyses included 218 patients. Anxious and depressed patients comprised 63.8 and 71.5 % of the sample, respectively. For the hypothetical model, the goodness-of-fit index = 0.91, normal fit index = 0.93, and comparative fit index = 0.90. The outcome was suitable for the recommended level, so the hypothetical model appeared to fit the data. In patients with MFS, the QOL was affected significantly by social support, disease-related factors, and biobehavioral factors. These variables explained 72.4 % of the QOL in patients with MFS. Biobehavioral factors had the strongest and most direct effects on QOL. CONCLUSION: To improve QOL in patients with MFS, comprehensive interventions are necessary to assess and manage biobehavioral factors, social support, and disease related factors. PMID- 27249939 TI - Neuromechanical response to spinal manipulation therapy: effects of a constant rate of force application. AB - BACKGROUND: Neuromechanical responses to spinal manipulation therapy (SMT) have been shown to be modulated through the variation of SMT biomechanical parameters: peak force, time to peak force, and preload force. Although rate of force application was modulated by the variation of these parameters, the assumption that neuromuscular responses are modulated by the rate of force application remains to be confirmed. Therefore, the purpose of the present study was to evaluate the effect of a constant rate of force application in neuromechanical responses to SMT in healthy adults. METHODS: Four SMT force-time profiles presenting different time to peak force and peak force, but with a constant rate of force application were applied on 25 healthy participants' T7 transverse processes. Muscular responses were recorded through surface electromyography electrodes (T6 and T8 levels), while vertebral displacements were assessed through pasted kinematic markers on T6 to T8 spinous processes. Effects of SMT force-time profiles on neuromechanical responses were assessed using repeated measures ANOVAs. RESULTS: There was no main effect of SMT force-time profile modulation on muscular responses (ps > .05) except for the left T8 (F (3, 72) = 3.23, p = .03) and left T6 (F (3, 72) = 2.94, p = .04). Muscular responses were significantly lower for the lowest peak force condition than the highest (for T8) or second highest (for T6). Analysis showed that increasing the SMT peak force (and concomitantly time to peak force) led to a significant vertebral displacement increase for the contacted vertebra (F T7 (1, 17) = 354.80, p < .001) and both adjacent vertebras (F T6 (1, 12) = 104.71, p < .001 and F T8 (1, 19) = 468.68, p < .001). CONCLUSION: This study showed that peak force modulation using constant rate of force application leads to similar neuromuscular responses. Coupled with previous investigations of SMT peak force and duration effects, the results suggest that neuromuscular responses to SMT are mostly influenced by the rate of force application, while peak force modulation yields changes in the vertebral displacement. Rate of force application should therefore be defined in future studies. Clinical implications of various SMT dosages in patients with spine related pain should also be investigated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02550132 . Registered 8 September 2015. PMID- 27249940 TI - Hypo-fractionated stereotactic radiotherapy alone using volumetric modulated arc therapy for patients with single, large brain metastases unsuitable for surgical resection. AB - BACKGROUND: Hypo-fractionated stereotactic radiotherapy (HSRT) is emerging as a valid treatment option for patients with single, large brain metastases (BMs). We analyzed a set of our patients treated with HSRT. The aim of this study was to evaluate local control (LC), brain distant progression (BDP), toxicity and overall survival (OS). METHODS: From July 2011 to May 2015, 102 patients underwent HSRT consisting of 27Gy/3fractions for lesions 2.1-3 cm and 32Gy/4 fractions for lesions 3.1-5 cm. Local progression was defined as increase of the enhancing abnormality on MRI, and distant progression as new brain metastases outside the irradiated volume. Toxicity in terms of radio-necrosis was assessed using contrast enhanced T1MRI, T2 weighted-MRI and perfusion- MRI. RESULT: The median maximum diameter of BM was 2.9 cm (range 2.1-5 cm), the median gross target volume (GTV) was 16.3 cm(3) and the median planning target volume (PTV) was 33.7 cm(3) The median,1,2-year local control rate was 30 months, 96, 96 %; the median, 1-2-year rate of BDP was 24 months, 12, 24 %; the median,1,2-year OS was 14 months, 69, 33 %. KPS and controlled extracranial disease were associated with significant survival benefit (p <0.01). Brain radio-necrosis occurred in six patients (5.8 %). CONCLUSION: In patients with single, large BMs unsuitable for surgical resection, HSRT is a safe and feasible treatment, with good brain local control and limited toxicity. PMID- 27249941 TI - Conservative dissipation: How important is the Jacobi identity in the dynamics? AB - Hamiltonian dynamics are characterized by a function, called the Hamiltonian, and a Poisson bracket. The Hamiltonian is a conserved quantity due to the anti symmetry of the Poisson bracket. The Poisson bracket satisfies the Jacobi identity which is usually more intricate and more complex to comprehend than the conservation of the Hamiltonian. Here, we investigate the importance of the Jacobi identity in the dynamics by considering three different types of conservative flows in R(3): Hamiltonian, almost-Poisson, and metriplectic. The comparison of their dynamics reveals the importance of the Jacobi identity in structuring the resulting phase space. PMID- 27249942 TI - Probing and exploiting the chaotic dynamics of a hydrodynamic photochemical oscillator to implement all the basic binary logic functions. AB - The convective motions within a solution of a photochromic spiro-oxazine being irradiated by UV only on the bottom part of its volume, give rise to aperiodic spectrophotometric dynamics. In this paper, we study three nonlinear properties of the aperiodic time series: permutation entropy, short-term predictability and long-term unpredictability, and degree distribution of the visibility graph networks. After ascertaining the extracted chaotic features, we show how the aperiodic time series can be exploited to implement all the fundamental two inputs binary logic functions (AND, OR, NAND, NOR, XOR, and XNOR) and some basic arithmetic operations (half-adder, full-adder, half-subtractor). This is possible due to the wide range of states a nonlinear system accesses in the course of its evolution. Therefore, the solution of the convective photochemical oscillator results in hardware for chaos-computing alternative to conventional complementary metal-oxide semiconductor-based integrated circuits. PMID- 27249943 TI - Heterogeneity and nearest-neighbor coupling can explain small-worldness and wave properties in pancreatic islets. AB - Many multicellular systems consist of coupled cells that work as a syncytium. The pancreatic islet of Langerhans is a well-studied example of such a microorgan. The islets are responsible for secretion of glucose-regulating hormones, mainly glucagon and insulin, which are released in distinct pulses. In order to observe pulsatile insulin secretion from the beta-cells within the islets, the cellular responses must be synchronized. It is now well established that gap junctions provide the electrical nearest-neighbor coupling that allows excitation waves to spread across islets to synchronize the beta-cell population. Surprisingly, functional coupling analysis of calcium responses in beta-cells shows small-world properties, i.e., a high degree of local coupling with a few long-range "short cut" connections that reduce the average path-length greatly. Here, we investigate how such long-range functional coupling can appear as a result of heterogeneity, nearest-neighbor coupling, and wave propagation. Heterogeneity is also able to explain a set of experimentally observed synchronization and wave properties without introducing all-or-none cell coupling and percolation theory. Our theoretical results highlight how local biological coupling can give rise to functional small-world properties via heterogeneity and wave propagation. PMID- 27249944 TI - On the existence of bifocal heteroclinic cycles in a class of four-dimensional piecewise affine systems. AB - Based on mathematical analysis, this paper provides a methodology to ensure the existence of heteroclinic cycles in a class of four-dimensional piecewise affine systems. In addition, examples are provided to illustrate the effectiveness of the method. PMID- 27249945 TI - Persistent topological features of dynamical systems. AB - Inspired by an early work of Muldoon et al., Physica D 65, 1-16 (1993), we present a general method for constructing simplicial complex from observed time series of dynamical systems based on the delay coordinate reconstruction procedure. The obtained simplicial complex preserves all pertinent topological features of the reconstructed phase space, and it may be analyzed from topological, combinatorial, and algebraic aspects. In focus of this study is the computation of homology of the invariant set of some well known dynamical systems that display chaotic behavior. Persistent homology of simplicial complex and its relationship with the embedding dimensions are examined by studying the lifetime of topological features and topological noise. The consistency of topological properties for different dynamic regimes and embedding dimensions is examined. The obtained results shed new light on the topological properties of the reconstructed phase space and open up new possibilities for application of advanced topological methods. The method presented here may be used as a generic method for constructing simplicial complex from a scalar time series that has a number of advantages compared to the mapping of the same time series to a complex network. PMID- 27249946 TI - Bifurcations and degenerate periodic points in a three dimensional chaotic fluid flow. AB - Analysis of the periodic points of a conservative periodic dynamical system uncovers the basic kinematic structure of the transport dynamics and identifies regions of local stability or chaos. While elliptic and hyperbolic points typically govern such behaviour in 3D systems, degenerate (parabolic) points also play an important role. These points represent a bifurcation in local stability and Lagrangian topology. In this study, we consider the ramifications of the two types of degenerate periodic points that occur in a model 3D fluid flow. (1) Period-tripling bifurcations occur when the local rotation angle associated with elliptic points is reversed, creating a reversal in the orientation of associated Lagrangian structures. Even though a single unstable point is created, the bifurcation in local stability has a large influence on local transport and the global arrangement of manifolds as the unstable degenerate point has three stable and three unstable directions, similar to hyperbolic points, and occurs at the intersection of three hyperbolic periodic lines. The presence of period-tripling bifurcation points indicates regions of both chaos and confinement, with the extent of each depending on the nature of the associated manifold intersections. (2) The second type of bifurcation occurs when periodic lines become tangent to local or global invariant surfaces. This bifurcation creates both saddle-centre bifurcations which can create both chaotic and stable regions, and period doubling bifurcations which are a common route to chaos in 2D systems. We provide conditions for the occurrence of these tangent bifurcations in 3D conservative systems, as well as constraints on the possible types of tangent bifurcation that can occur based on topological considerations. PMID- 27249947 TI - Visibility graphlet approach to chaotic time series. AB - Many novel methods have been proposed for mapping time series into complex networks. Although some dynamical behaviors can be effectively captured by existing approaches, the preservation and tracking of the temporal behaviors of a chaotic system remains an open problem. In this work, we extended the visibility graphlet approach to investigate both discrete and continuous chaotic time series. We applied visibility graphlets to capture the reconstructed local states, so that each is treated as a node and tracked downstream to create a temporal chain link. Our empirical findings show that the approach accurately captures the dynamical properties of chaotic systems. Networks constructed from periodic dynamic phases all converge to regular networks and to unique network structures for each model in the chaotic zones. Furthermore, our results show that the characterization of chaotic and non-chaotic zones in the Lorenz system corresponds to the maximal Lyapunov exponent, thus providing a simple and straightforward way to analyze chaotic systems. PMID- 27249948 TI - Noise induced stabilization of chaotic free-running laser diode. AB - In this paper, we investigate theoretically the stabilization of a free-running vertical-cavity surface-emitting laser exhibiting polarization chaos dynamics. We report the existence of a boundary isolating the chaotic attractor on one side and a steady-state on the other side and identify the unstable periodic orbit playing the role of separatrix. In addition, we highlight a small range of parameters where the chaotic attractor passes through this boundary, and therefore where chaos only appears as a transient behaviour. Then, including the effect of spontaneous emission noise in the laser, we demonstrate that, for realistic levels of noise, the system is systematically pushed over the separating solution. As a result, we show that the chaotic dynamics cannot be sustained unless the steady-state on the other side of the separatrix becomes unstable. Finally, we link the stability of this steady-state to a small value of the birefringence in the laser cavity and discuss the significance of this result on future experimental work. PMID- 27249949 TI - Reconstruction of the modified discrete Langevin equation from persistent time series. AB - The discrete Langevin-type equation, which can describe persistent processes, was introduced. The procedure of reconstruction of the equation from time series was proposed and tested on synthetic data, with short and long-tail distributions, generated by different Langevin equations. Corrections due to the finite sampling rates were derived. For an exemplary meteorological time series, an appropriate Langevin equation, which constitutes a stochastic macroscopic model of the phenomenon, was reconstructed. PMID- 27249950 TI - Objective Eulerian coherent structures. AB - We define objective Eulerian Coherent Structures (OECSs) in two-dimensional, non autonomous dynamical systems as the instantaneously most influential material curves. Specifically, OECSs are stationary curves of the averaged instantaneous material stretching-rate or material shearing-rate functionals. From these objective (frame-invariant) variational principles, we obtain explicit differential equations for hyperbolic, elliptic, and parabolic OECSs. As an illustration, we compute OECSs in an unsteady ocean velocity data set. In comparison to structures suggested by other common Eulerian diagnostic tools, we find OECSs to be the correct short-term cores of observed trajectory deformation patterns. PMID- 27249951 TI - Waves transmission and amplification in an electrical model of microtubules. AB - Inspired by standard electrophysiological models of microtubules, a discrete nonlinear equation for ionic wave propagation that incorporates a negative nonlinear resistance is presented. The conditions for wave propagation in forbidden band gap are analyzed without and with dissipation. The nonlinear response manifold method is used to determine the supratransmission threshold of the case of study without dissipation. This threshold is found to be similar to the value obtained by analytical methods. With the dissipation, the monitoring of the accumulated energy is used to estimate the infratransmission threshold. It appears that the value of the supratransmission threshold can be lower than the value of the infratransmission threshold. The system is found to amplify significantly the amplitude of the input signal, thus confirming known experimental results. Nevertheless, a proper choice of the parameter of the nonlinear resistance is required for further validation of our results. A possible biological implication of the obtained results is presented. PMID- 27249952 TI - The circadian rhythm induced by the heterogeneous network structure of the suprachiasmatic nucleus. AB - In mammals, the master clock is located in the suprachiasmatic nucleus (SCN), which is composed of about 20 000 nonidentical neuronal oscillators expressing different intrinsic periods. These neurons are coupled through neurotransmitters to form a network consisting of two subgroups, i.e., a ventrolateral (VL) subgroup and a dorsomedial (DM) subgroup. The VL contains about 25% SCN neurons that receive photic input from the retina, and the DM comprises the remaining 75% SCN neurons which are coupled to the VL. The synapses from the VL to the DM are evidently denser than that from the DM to the VL, in which the VL dominates the DM. Therefore, the SCN is a heterogeneous network where the neurons of the VL are linked with a large number of SCN neurons. In the present study, we mimicked the SCN network based on Goodwin model considering four types of networks including an all-to-all network, a Newman-Watts (NW) small world network, an Erdos-Renyi (ER) random network, and a Barabasi-Albert (BA) scale free network. We found that the circadian rhythm was induced in the BA, ER, and NW networks, while the circadian rhythm was absent in the all-to-all network with weak cellular coupling, where the amplitude of the circadian rhythm is largest in the BA network which is most heterogeneous in the network structure. Our finding provides an alternative explanation for the induction or enhancement of circadian rhythm by the heterogeneity of the network structure. PMID- 27249953 TI - In vivo anti-inflammatory activity of caffeoylquinic acid derivatives from Solidago virgaurea in rats. AB - CONTEXT: Solidago virgaurea L. (Asteraceae) is traditionally used as an anti inflammatory for the treatment of various symptoms including cystitis. However, little is known concerning the constituents responsible for this activity and the mechanism of their action. OBJECTIVE: To assess the anti-inflammatory activity of the phenolic-rich fraction of S. virgaurea aerial parts in rats, isolate and assess the activity of the major compounds present. MATERIALS AND METHODS: An HPLC method was developed for the analysis of the phenolic-rich fraction (EtFr). The in vivo anti-inflammatory activity of the EtFr and four isolated compounds (at 25 and 50 mg/kg) were assessed in adult male rats using the carrageenan induced rat paw oedema model. The levels of the pro-inflammatory cytokines (TNF alpha and IL-1beta) were measured using ELISA. RESULTS: 3,5-O-Dicaffeoylquinic acid (1), 3,4-O-dicaffeoylquinic acid (2), 3,4,5-O-tricaffeoylquinic acid (3) and 4,5-O-dicaffeoylquinic acid (4) were isolated from EtFr. Compound 3 (50 mg/kg) showed a highly significant activity in inhibiting the oedema volume after 3 h (88% of the activity of indomethacin at 10 mg/kg). The EtFr and the isolated compounds largely inhibited the excessive production of the inflammatory mediators TNF-alpha and IL-1beta. DISCUSSION AND CONCLUSION: This is the first report of 3,4,5-tri-O-caffeoylquinic acid (3) in Solidago species. The tricaffeoylquinic acid (3) showed a significantly higher activity than the other three dicaffeoylquinic acids (1, 2, 4) and indomethacin in reduction of TNF-alpha and IL-1beta concentrations (8.44 +/- 0.62 and 5.83 +/- 0.57 pg/mL compared to 12.60 +/- 1.30 and 52.91 +/- 5.20 pg/mL induced by indomethacin, respectively). PMID- 27249954 TI - CORR Insights((r)): How Does Wear Rate Compare in Well-functioning Total Hip and Knee Replacements? A Postmortem Polyethylene Liner Study. PMID- 27249955 TI - Periprosthetic Joint Infection in Hip Arthroplasty: Is There an Association Between Infection and Bearing Surface Type? AB - BACKGROUND: Preliminary studies have raised the question of whether certain prosthetic biomaterials used in total hip arthroplasty (THA) bearings are associated with increased risk of periprosthetic joint infection (PJI). For example, some observational data suggest the risk of PJI is higher with metal-on metal bearings. However, it is not known whether other bearings-including ceramic bearings or metal-on-polyethylene bearings-may be associated with a higher or lower risk of PJI. QUESTIONS/PURPOSES: The objective of this study was to use a national arthroplasty registry to assess whether the choice of bearings-metal-on polyethylene (MoP), ceramic-on-polyethylene (CoP), ceramic-on-ceramic (CoC), or metal-on-metal (MoM)-is associated with differences in the risk of revision for deep infection, either (1) within 6 months or (2) over the entire period of observation, which spanned 15 years. METHODS: Data from primary THAs were extracted from the New Zealand Joint Registry over a 15-year period. A total of 97,889 hips were available for analysis. Inclusion criterion was degenerative joint disease; exclusion criteria were previous surgery, trauma, and any other diagnosis (12,566 hips). We also excluded a small group of ceramic-on-metal THAs (429) with short followup. The median observation period of the selected group of hips (84,894) was 9 years (range, 1-15 years). The mean age of patients was 68 years (SD +/- 11 years), and 52% were women. There were 54,409 (64%) MoP, 16,503 (19%) CoP, 9051 (11%) CoC, and 4931 (6%) MoM hip arthroplasties. Four hundred one hips were revised for deep infection. A multivariate assessment was carried out including the following risks factors available for analysis: age, sex, operating room type, use of body exhaust suits, THA fixation mode, and surgeon volume. Because of late introduction of data collection in the Registry, we were unable to include body mass index (BMI, recording started 2010) and medical comorbidities according to the American Society of Anesthesiologists class (ASA, recording started 2005) in the multivariate analysis. RESULTS: The rate of early PJI (< 6 months) did not differ by bearing surface. In contrast, we observed a difference over the total observation period. Within the first 6 months after the index surgery, CoC THAs were not associated with a lower risk of revision for PJI (p = 0.118) when compared with CoP (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.50-3.41), MoP (HR, 2.10; CI, 0.91-4.82), and MoM (HR, 2.04; CI, 0.69-6.09). When the whole observation period was considered, CoC hips were associated with a lower risk of revision for deep infection when compared with CoP (HR, 1.30; CI, 0.78-2.18; p = 0.01), MoP (HR, 1.75; CI, 1.07-2.86; p = 0.02), and MoM (HR, 2.12; CI, 1.23-3.65; p = 0.008). CONCLUSIONS: Our finding associating CoC THA bearings with a lower risk of infection after THA must be considered very preliminary, and we caution readers against attributing all of the observed difference to the bearing surface. It is possible that some or all of the observed difference associated with bearing type may have been driven by other factors such as ASA and BMI, which could not be included in our multivariate analysis, and so future registry studies on this topic must assess those variables carefully. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27249956 TI - Relationships between poverty and AIDS Illness in South Africa: an investigation of urban and rural households in KwaZulu-Natal. AB - The association between poverty and HIV/AIDS in Sub-Saharan Africa remains contested. A better understanding of the relationship between the prevalence of poverty and the disease is essential for addressing prevention, treatment, and care. The present study interrogates this relationship, using a cross-sectional survey of 2477 households in urban and rural KwaZulu-Natal, South Africa. Structural equation modelling was employed to estimate the correlations between poverty and AIDS illness. The analysis revealed a correlation of rpb = 0.23, denoting that a higher level of household poverty was associated with a higher likelihood of being AIDS-unwell. Post hoc t-test showed that receipt of a disability grant by AIDS-affected households was associated with significantly lower poverty, compared to AIDS-affected households not receiving the grant, t(654) = 3.67, p < .01. Geographic location was found to confound the correlation: the strength of the relationship between poverty and AIDS was decreased to rpb = 0.15 (p < .001) for the urban and rpb = 0.16 (p < .001) for the rural sub-population. Findings suggest the importance of two sets of policies: those that address the potential upstream risk of poverty through economic interventions, and those that alleviate the impoverishing effects of AIDS illness for affected households. PMID- 27249957 TI - CHRNA7 Polymorphisms and Dementia Risk: Interactions with Apolipoprotein epsilon4 and Cigarette Smoking. AB - alpha7 nicotinic acetylcholine receptor (alpha7nAChR, encoded by CHRNA7) is involved in dementia pathogenesis through cholinergic neurotransmission, neuroprotection and interactions with amyloid-beta. Smoking promotes atherosclerosis and increases dementia risk, but nicotine exerts neuroprotective effect via alpha7nAChR in preclinical studies. No studies explored the gene-gene, gene-environment interactions between CHRNA7 polymorphism, apolipoprotein E (APOE) epsilon4 status and smoking on dementia risk. This case-control study recruited 254 late-onset Alzheimer's disease (LOAD) and 115 vascular dementia (VaD) cases (age >=65) from the neurology clinics of three teaching hospitals in Taiwan during 2007-2010. Controls (N = 435) were recruited from health checkup programs and volunteers during the same period. Nine CHRNA7 haplotype-tagging single nucleotide polymorphisms representative for Taiwanese were genotyped. Among APOE epsilon4 non-carriers, CHRNA7 rs7179008 variant carriers had significantly decreased LOAD risk after correction for multiple tests (GG + AG vs. AA: adjusted odds ratio = 0.29, 95% confidence interval = 0.13-0.64, P = 0.002). Similar findings were observed for carriers of GT haplotype in CHRNA7 block4. A significant interaction was found between rs7179008, GT haplotype in block4 and APOE epsilon4 on LOAD risk. rs7179008 variant also reduced the detrimental effect of smoking on LOAD risk. No significant association was found between CHRNA7 and VaD. These findings help to understand dementia pathogenesis. PMID- 27249960 TI - Effects of high three pro-nuclei (3PN) proportion incidence on clinical outcomes in the fresh cleavage-stage and blastocyst-stage embryo transfer (ET) cycles. AB - OBJECTIVES: The aim of this study was to explore the effect of three pro-nuclei (3PN) incidence on clinical outcomes in the fresh cleavage-stage embryo transfer (CSET) and blastocyst-stage embryo transfer (BSET) cycles. METHODS: This retrospective cohort study included 1427 CSET cycles, 632 BSET cycles, and 313 elective single BSET cycles from January 2013 to June 2015. The patients were divided into two groups as follows: Group 1 included patients with no 3PN zygotes and Group 2 included patients with >20% 3PN zygotes. RESULTS: We observed that the fertilization rate was significantly lower in 3PN = 0% than 3PN > 20% group (p < 0.05), but the day-3 grade I + II embryo and day-3 grade I + II + III embryo rates were not significantly different between 3PN = 0% and 3PN > 20% group (p > 0.05). Interestingly, in the CSET, the implantation (42.87% and 41.76%, p = 0.585) and clinical pregnancy (59.94% and 58.25%, p = 0.538) rates were not significantly different between two groups. In the BSET, the implantation (61.93% and 49.62%, p < 0.001) and clinical pregnancy rates (69.45% and 61.02%, p = 0.043) were significantly higher in 3PN = 0% than 3PN > 20% group. In the elective single BSET, the implantation (68.91% and 61.33%, p = 0.223) and clinical pregnancy rates (68.48% and 61.33%, p = 0.251) were higher in 3PN = 0% than 3PN > 20% group, but there was no significant difference. CONCLUSIONS: We concluded that a high 3PN incidence may predict poor outcomes in BSET but not CSET cleavage-stage. PMID- 27249958 TI - The channel catfish genome sequence provides insights into the evolution of scale formation in teleosts. AB - Catfish represent 12% of teleost or 6.3% of all vertebrate species, and are of enormous economic value. Here we report a high-quality reference genome sequence of channel catfish (Ictalurus punctatus), the major aquaculture species in the US. The reference genome sequence was validated by genetic mapping of 54,000 SNPs, and annotated with 26,661 predicted protein-coding genes. Through comparative analysis of genomes and transcriptomes of scaled and scaleless fish and scale regeneration experiments, we address the genomic basis for the most striking physical characteristic of catfish, the evolutionary loss of scales and provide evidence that lack of secretory calcium-binding phosphoproteins accounts for the evolutionary loss of scales in catfish. The channel catfish reference genome sequence, along with two additional genome sequences and transcriptomes of scaled catfishes, provide crucial resources for evolutionary and biological studies. This work also demonstrates the power of comparative subtraction of candidate genes for traits of structural significance. PMID- 27249959 TI - Lobe-Specific Nodal Dissection for Clinical Stage I and II NSCLC: Japanese Multi Institutional Retrospective Study Using a Propensity Score Analysis. AB - OBJECTIVES: The purpose of this study was to assess the surgical outcomes according to the extent of mediastinal lymph node dissection for patients with NSCLC by using a nationwide registry database. METHODS: From among 11,663 patients in a Japanese lung cancer registry study for 2004, 5392 patients with clinical stage (c-stage) I or II NSCLC that was completely resected by lobectomy and either systematic (SND) or lobe-specific nodal dissection (LSD) were enrolled. Patients who received preoperative therapy or had middle lobe tumor were excluded. In the LSD group, inferior mediastinal (subcarinal) nodes were not dissected for upper lobe tumors, and superior mediastinal nodes were not dissected for lower lobe tumors. To reduce the selection bias, an inverse probability of treatment weighting method using a propensity score was implemented. RESULTS: LSD and SND were performed in 1268 patients (23.5%) and 4124 patients (76.5%), respectively. The LSD group included more upper lobe and c stage I tumors and less pathological N2 disease than the SND group. Extended pathological N2 disease outside LSD area was found in 3.2% of the SND group. The 5-year overall survival was 81.5% in the LSD group and 75.9% in the SND group. An inverse probability of treatment weighting-adjusted Cox model showed that LSD did not have a negative prognostic impact and instead was associated with favorable survival (hazard ratio = 0.68, 95% confidence interval: 0.60-0.77). CONCLUSIONS: This retrospective registry study suggested that LSD is an alternative to SND for selected patients with c-stage I or II NSCLC. Future prospective studies are warranted to determine whether LSD is applicable and provides clinical benefit for the general population of patients with c-stage I or II NSCLC. PMID- 27249961 TI - X-ray characterization of mesophases of human telomeric G-quadruplexes and other DNA analogues. AB - Observed in the folds of guanine-rich oligonucleotides, non-canonical G quadruplex structures are based on G-quartets formed by hydrogen bonding and cation-coordination of guanosines. In dilute 5'-guanosine monophosphate (GMP) solutions, G-quartets form by the self-assembly of four GMP nucleotides. We use x ray diffraction to characterize the columnar liquid-crystalline mesophases in concentrated solutions of various model G-quadruplexes. We then probe the transitions between mesophases by varying the PEG solution osmotic pressure, thus mimicking in vivo molecular crowding conditions. Using the GMP-quadruplex, built by the stacking of G-quartets with no covalent linking between them, as the baseline, we report the liquid-crystalline phase behaviors of two other related G quadruplexes: (i) the intramolecular parallel-stranded G-quadruplex formed by the 22-mer four-repeat human telomeric sequence AG3(TTAG3)3 and (ii) the intermolecular parallel-stranded G-quadruplex formed by the TG4T oligonucleotides. Finally, we compare the mesophases of the G-quadruplexes, under PEG-induced crowding conditions, with the corresponding mesophases of the canonical duplex and triplex DNA analogues. PMID- 27249962 TI - Continued transmission of Pseudomonas aeruginosa from a wash hand basin tap in a critical care unit. AB - Pseudomonas aeruginosa is an important nosocomial pathogen, colonizing hospital water supplies including taps and sinks. We report a cluster of P. aeruginosa acquisitions during a period of five months from tap water to patients occupying the same burns single room in a critical care unit. Pseudomonas aeruginosa cultured from clinical isolates from four different patients was indistinguishable from water strains by pulsed-field gel electrophoresis. Water outlets in critical care may be a source of P. aeruginosa despite following the national guidance, and updated guidance and improved control measures are needed to reduce the risks of transmission to patients. PMID- 27249963 TI - Electrocotyle whittingtoni n. gen., n. sp. (Monogenea: Monocotylidae: Heterocotylinae) from the gills of a captive onefin electric ray, Narke capensis (Narkidae) at Two Oceans Aquarium, Cape Town, South Africa. AB - Electrocotyle whittingtoni n. gen., n. sp. (Monogenea: Monocotylidae) is described from the gills of a captive female onefin electric ray, Narke capensis, collected for exhibition at Two Oceans Aquarium in Cape Town, South Africa. Electrocotyle n. gen. is most similar to the heterocotyline genera Heterocotyle and Potamotrygonocotyle but could not be accommodated easily in either of these groups. The new genus is characterised by a haptor with one central and eight peripheral loculi, four unsclerotised structures on the dorsal surface of the haptor, a single unsclerotised non-sinous ridge on the ventral surface of the haptoral septa, large hamuli with a long handle and reduced guard, a vagina with sclerotised walls, and tetrahedral eggs. Molecular phylogenetic analyses based on 28S sequences strongly support the separate genus status of Electrocotyle n. gen and thus support our morphological conclusion. The Heterocotylinae is amended to accommodate the new genus, and the new species is fully described and illustrated herein. This is the first record of a monocotylid from the Narkidae. Electrocotyle whittingtoni n. gen. n. sp. is considered potentially pathogenic given its negative impact on the health of its captive host kept in the quarantine facility at Two Oceans Aquarium. PMID- 27249964 TI - Fresh fruits, vegetables and mushrooms as transmission vehicles for Echinococcus multilocularis in highly endemic areas of Poland: reply to concerns. AB - Echinococcus multilocularis is a tapeworm that may cause alveolar echinococcosis (AE), one of the most dangerous parasitic zoonoses. As in the case of other foodborne diseases, unwashed fruits and vegetables, contaminated with dispersed forms of E. multilocularis, may serve as an important transmission route for this parasite. In this article, we reply to the incorrect interpretation of results of our study concerning the detection of E. multilocularis DNA in fresh fruit, vegetable and mushroom samples collected from the highly endemic areas of the Warmia-Masuria Province, Poland, to dispel any doubts. The accusations formulated by the commentators concerning our paper are unfounded; moreover, these commentators demand information which was beyond the purview of our study. Making generalisations and drawing far-reaching conclusions from our work is also unjustified. The majority of positive samples were found in only a few hyperendemic communities; this information corresponds with the highest number of both infected foxes and AE cases in humans recorded in this area. Our findings indicate that E. multilocularis is present in the environment and may create a potential risk for the inhabitants. These people should simply be informed to wash fruits and vegetables before eating. No additional far-reaching conclusions should be drawn from our data. We believe these commentators needlessly misinterpreted our results and disseminated misleading information. Nevertheless, we would like to encourage any readers simply to contact us if any aspects of our study are unclear. PMID- 27249965 TI - Improving detection of avian malaria from host blood: a step towards a standardised protocol for diagnostics. AB - Avian malaria, caused by Plasmodium spp., has been linked to the mortality and population-level declines in native birds in some regions. While molecular diagnostic methods have greatly improved our ability to detect infections of both human and bird malaria, failing to identify false negatives remains an important handicap, particularly for avian malaria due to host DNA presence in the bird blood cells. In an attempt to improve the accuracy of diagnostics by PCR, we evaluated the performance of a commercial silica-membrane-based DNA extraction kit by modifying the protocol with four unpooled elution volume alternatives. Our results suggest that the best template is the DNA extract obtained from the second eluate of a first 50 MUL elution step. In one case, the only band visible was from this second eluate and, thus, may not have been identified as positive for Plasmodium spp. if a different elution protocol had been followed. Our results are likely explained by the concept of size exclusion chromatography by which particles of different sizes will elute at different rates. Overall, first elution templates may consist of a lower ratio of parasite to host DNA, while second eluates may contain a higher parasite to host DNA ratio. A low ratio of parasite to host DNA is a concern in detecting chronic infections, in which birds typically carry low levels of parasitemia, making accurate diagnostics imperative when identifying reservoirs of disease that could lead to spillback events. PMID- 27249966 TI - Benzimidazole resistance in Haemonchus contortus recovered from farmed red deer. AB - Thirty Haemonchus contortus male worms were collected from farmed red deer yearlings in order to determine whether routine administration of albendazole for a long-term period (17 years) could select anthelmintic resistance. PCR-RFLP method based on single-nucleotide polymorphism of codon 200 in isotype 1 beta tubulin gene (Phe200Tyr) was applied. The results showed a significant frequency of either the resistant allele (85 %) or the homozygous resistant genotype (70 %). By chi-square test, Hardy-Weinberg equilibrium of the population was accepted (p = 0.334, power of test 0.01). True prevalence of the resistant genotype (RR) was estimated to be 46.5-87.2 % (confidence interval 95 %) calculated by Sterne's exact method. These results confirmed that long-term use of benzimidazoles could change the relative allele frequency of genes associated with drug resistance and may cause a large-scale spread of the resistant allele. To our knowledge, this study supported benzimidazole resistance in Haemonchus contortus in red deer for the first time. PMID- 27249968 TI - Erratum to: Detection of Dirofilaria repens and Dirofilaria immitis DNA in mosquitoes from Belarus. PMID- 27249967 TI - Antileishmanial activity of antiretroviral drugs combined with miltefosine. AB - Co-infection of Leishmaniasis, a neglected tropical disease, with human immunodeficiency virus (HIV) has hindered treatment efficacy. In this study, we aim to evaluate the antileishmanial activity of two protease inhibitors (darunavir and atazanavir) and four reverse transcriptase inhibitors (tenofovir, efavirenz, neviraprine, and delavirdine mesylate) on Leishmania infantum. The activity of different antiretrovirals combinations and of antiretroviral with miltefosine, a drug used on leishmaniasis treatment, was also evaluated. Only two non-nucleoside reverse transcriptase inhibitors (NNRTIs) were active on L. infantum. Efavirenz showed the best antileishmanial activity on promastigotes cells with IC50 value of 26.1 MUM followed by delavirdine mesylate with an IC50 value of 136.2 MUM. Neviraprine, tenofovir, atazanavir, and darunavir were not active at the concentrations tested (IC50 > 200 MUM). The efavirenz also showed high antileishmanial activity on intramacrophage amastigotes with IC50 of 12.59 MUM. The interaction of efavirenz with miltefosine improved antileishmanial activity on promastigotes and intracellular amastigotes (IC50 values of 11. 8 MUM and 8.89 MUM, respectively). These results suggest that combined-therapy including efavirenz and miltefosine could be alternative options for treating Leishmaniasis and Leishmania/HIV co-infections. PMID- 27249969 TI - Rectal Calcified Fibrous Tumor Diagnosed After Endoscopic Submucosal Dissection of a Suspected Neuroendocrine Tumor. PMID- 27249970 TI - Esophageal Perforation From a Gunshot Wound. PMID- 27249971 TI - Pancreatic Islet Cells Mimicking Hepatic Metastases. PMID- 27249972 TI - A Splenic UFO: Intrasplenic Epithelioid Mesothelioma. PMID- 27249973 TI - An Alcoholic With Hematochezia From an Accidental Cocktail Sword Ingestion. PMID- 27249974 TI - Endoscopic Image After Subselective Embolization of a Bleeding Colonic Diverticulum. PMID- 27249975 TI - Positive PET in a Patient With Esophageal Leiomyoma. PMID- 27249976 TI - MRI Patterns in a Case of 6-Thioguanine-Related Hepatic Sinusoidal Obstruction Syndrome. PMID- 27249977 TI - Use of PGA Sheets in the Endoscopic Closure of a Perforation After Endoscopic Submucosal Dissection for Gastric-Tube Cancer. PMID- 27249982 TI - Editorial: Endoscopic Resection of Upper Gastrointestinal Subepithelial Tumors: Promising New Endoscopic Techniques-Are They Here to Stay? AB - Endoscopic resection of gastrointestinal subepithelial tumors originating from muscularis propria is feasible and safe if performed by experienced hands. Large tumors with predominantly extraluminal growth and extensive connection of the tumor base with the muscularis propria are associated with less complete resection and more complications. An intact tumor capsule should be used as an indication of complete resection. Free air on images after endoscopic full thickness resection may not be an accident. Submucosal endoscopic procedures are promising therapeutic procedures but are potentially associated with serious complications. Therefore, advanced endoscopic training is needed in order to perform them correctly and safely. PMID- 27249983 TI - Editorial: A New Spin on Magnetic Resonance Elastography. AB - The development of hepatic fibrosis is the hallmark of liver disease progression. Identifying fibrosis across the spectrum, from early stages to cirrhosis has become a major unmet need. Newer imaging techniques that measure liver elastography (stiffness) as a surrogate of fibrosis seem to outperform serum tests. The current study compares two-dimensional (2D) gradient-recalled echo magnetic resonance elastography (MRE) to three-dimensional (3D) spin-echo echo planar imaging MRE. 3D-SE-EPI MRE was able to image more liver volume in less time with fewer technical failures. The current study demonstrates that 3D-SE-EPI MRE appears marginally superior to 2D-GRE and may evolve into the new gold standard. PMID- 27249984 TI - Right- versus Conventional Left-Sided Starting Position for Colonoscopy: The Issues to Be Considered. PMID- 27249985 TI - Reply to Koklu et al. PMID- 27249986 TI - Right Lateral Decubitus for Routine Colonoscopy: Beware the Potential Risk of Aspiration. PMID- 27249987 TI - Reply to Fusaroli. PMID- 27249988 TI - Screening and Surveillance for Barrett's Esophagus: When Will We Reach the Horizon? PMID- 27249989 TI - Response to Braillon et al. PMID- 27249990 TI - Simple Clinical Colitis Activity Index: Accurate Assessment of Inflammatory Burden or Reflection of Low Mood and Somatoform Behavior? PMID- 27249991 TI - Response to Gracie and Ford. PMID- 27249992 TI - Endoscopic Submucosal Dissection Is Superior to Endoscopic Mucosal Resection for Histologic Evaluation of Barrett's Esophagus and Barrett's-Related Neoplasia. PMID- 27249993 TI - Direct Observed Therapy of Chronic Hepatitis C With Interferon-Free All-Oral Regimens at a Low-Threshold Drug Treatment Facility-a New Concept for Treatment of Patients With Borderline Compliance Receiving Opioid Substitution Therapy. PMID- 27249994 TI - What Is the Appropriate Sample Size One Should Submit from EUS Biopsies for Genotyping Lymphomas? Ask Your Pathologist before Embarking. PMID- 27249995 TI - Why Referring Physicians Rarely Diagnose Gastrointestinal Diseases. PMID- 27249998 TI - Corrigendum: Diagnostic Performance of the Simple Clinical Colitis Activity Index Self-Administered Online at Home by Patients With Ulcerative Colitis: CRONICA-UC Study. PMID- 27249999 TI - Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation. AB - Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to (1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, (2) characterize the type of inflammatory response present, and (3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e., immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy, and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore, biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human breast cancer. These findings may carry relevance in the clinical management of breast cancer. PMID- 27250000 TI - Validation of an oligo-gene signature for the prognostic stratification of ductal carcinoma in situ (DCIS). AB - Current evidence suggests that the majority of DCIS lesions do not progress to invasive carcinoma, and overtreatment of DCIS is a significant problem. We previously reported an 8-gene signature that differentiated microdissected low grade (LG) DCIS lesions with and without associated stromal invasion, based on differential DNA copy number changes detected by quantitative (q) PCR. The current study was undertaken to validate our candidate breast cancer invasion gene panel in a larger series of non-microdissected LG DCIS cases, and to investigate its potential utility in intermediate-grade (IG) and high-grade (HG) DCIS. Representative paraffin blocks were selected from 267 resected DCIS cases with 5-15 years of follow-up (139 pure DCIS ["PD"] and 128 mixed DCIS with associated invasion ["MD"]). These included 171 LG, 46 IG and 50 HG DCIS cases. Gene copy number changes were determined by qPCR, and their differential distribution in the PD and MD subgroups was evaluated. As an alternate platform, we employed immunohistochemistry (IHC). Novel IHC assays were developed for all eight candidate genes, and increased or reduced protein expression was manually scored. Separate multi-gene models were developed for qPCR and IHC to distinguish progressing and non-progressing DCIS lesions. By qPCR analysis, a panel of six genes, as well as CELSR1 alone (a potential invasion suppressor), differentiated PD and MD cases in LG and IG, but not in HG DCIS. By IHC, a panel of three genes, as well as GRAP2 alone (a potential invasion promoter), also distinguished PD and MD cases in LG and IG, but not in HG DCIS. The combination of CELSR1 (by qPCR) and GRAP2 (by IHC) had the best discriminatory power (p = 0.00004). Assays testing either or both of these genes have the potential to become important adjuncts for choosing appropriate treatment for LG/IG DCIS patients. PMID- 27250001 TI - A single-center, randomized, parallel controlled study comparing the efficacy and safety aspects of three anthracycline-based regimens as neoadjuvant chemotherapy in primary breast cancer. AB - This study aimed to compare the efficacy and safety aspects of three anthracycline-based regimens as neoadjuvant chemotherapy in primary breast cancer. Five-hundred and one patients with clinical stage I-III invasive breast cancer were randomly assigned to receive four cycles of neoadjuvant chemotherapy with either CEFci arm (5-Fu 200 mg/m(2) daily by 24-h continuous infusion and epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenous bolus on day 1), CEF arm (cyclophosphamide 600 mg/m(2), epirubicin 100 mg/m(2), and 5-Fu 600 mg/m(2) i.v. on day 1), or EC arm (epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1). The pathologic responses to chemotherapy were assessed according to the Miller and Payne grading system (MP). A total of 485 patients were included in the intent-to-treat population. Breast pathologic complete response (pCR) rate was 18.9 % (31/164) in CEFci arm, 15.0 % (24/160) in CEF arm, and 12.4 % (20/161) in EC arm (P = 0.266). MP grading system 4/5 response rate was significantly higher in CEFci arm than that in CEF arm and EC arm (44.5, 31.3 and 27.3 %, respectively, P = 0.003). There was no significant difference on grade III/IV neutropenia among three arms (P = 0.538), but thrombocytopenia, decreased hemoglobin, and elevated aminotransferase appeared to be observed more in CEFci arm (P = 0.040, 0.059, and 0.073, respectively). CEFci did not reach a higher pCR rate compared with CEF or EC in patients with primary breast cancer. The potential advantage of CEFci in improving pathologic response still requires further research. The accompanied hematologic and biochemical toxicities, and the catheter-related complications should also be noted. PMID- 27250002 TI - Development of the Mexican Heart Team: The Long and Winding Road. AB - Heart failure (HF) is the leading cause of death worldwide. Efforts to decrease HF mortality rates include a multidisciplinary approach management. Although evidence suggests that this has been an optimal strategy for treating HF, the model remains not widely implanted. The current article explores the rationale behind the formation of a Heart Team in a developing country and its development despite the lack of an allocated budget. PMID- 27250004 TI - Diversity of nitrogen fixation strategies in Mediterranean legumes. AB - Symbiotic N2 fixation (SNF) brings nitrogen into ecosystems, fuelling much of the world's agriculture(1) and sustaining carbon storage(2,3). However, it can also cause nitrogen saturation, exacerbating eutrophication and greenhouse warming(4 7). The balance of these effects depends on the degree to which N2-fixing plants adjust how much N2 they fix based on their needs (their SNF 'strategies')(5,6). Genetic, biochemical and physiological details of SNF are well known for certain economically important species(8,9), but the diversity of N2-fixing plants(10) and bacteria(11) is enormous, and little is known about most N2-fixing symbioses in natural ecosystems(12). Here, we show that co-occurring, closely related herbs exhibit diverse SNF strategies. In response to a nitrogen supply gradient, four species fixed less N2 than they needed (over-regulation), two fixed what they needed (facultative) and two did not downregulate SNF (obligate). No species downregulated but fixed more N2 than it needed (under-regulation or incomplete downregulation), but some species under-regulated or incompletely downregulated structural allocation to SNF. In fact, most species maintained nodules (the root structures that house symbionts) when they did not fix N2, suggesting decoupling of SNF activity and structure. Simulations showed that over-regulation of SNF activity is more adaptive than under-regulation or incomplete downregulation, and that different strategies have wildly different effects on ecosystem-level nitrogen cycling. PMID- 27250005 TI - Role of auxiliary proteins in Rubisco biogenesis and function. AB - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyses the conversion of atmospheric CO2 into organic compounds during photosynthesis. Despite its pivotal role in plant metabolism, Rubisco is an inefficient enzyme and has therefore been a key target in bioengineering efforts to improve crop yields. Much has been learnt about the complex cellular machinery involved in Rubisco assembly and metabolic repair over recent years. The simple form of Rubisco found in certain bacteria and dinoflagellates comprises two large subunits, and generally requires the chaperonin system for folding. However, the evolution of hexadecameric Rubisco, which comprises eight large and eight small subunits, from its dimeric precursor has rendered Rubisco in most plants, algae, cyanobacteria and proteobacteria dependent on an array of additional factors. These auxiliary factors include several chaperones for assembly as well as ATPases of the AAA+ family for functional maintenance. An integrated view of the pathways underlying Rubisco biogenesis and repair will pave the way for efforts to improve the enzyme with the goal of increasing crop yields. PMID- 27250007 TI - Asiatic cotton can generate similar economic benefits to Bt cotton under rainfed conditions. AB - American cotton (Gossypium hirsutum L.), transformed with Bacillus thuringiensis Cry genes (Bt G. hirsutum) that confer resistance to lepidopteran pests, is extensively cultivated worldwide. In India, transgenic Bt G. hirsutum was commercially released in 2002 and by 2014 95% of farmers had adopted Bt G. hirsutum(1). The economic benefits of Bt G. hirsutum over non-Bt G. hirsutum are well documented and include increase in yields, increase in farmers' net revenue and reduction in pesticide application against lepidopteran pests(2-9). However, it is unclear to what extent irrigation influences the performance of Bt G. hirsutum on smallholder farming in India, and if, in the absence of irrigation, growing Bt G. hirsutum provides greater economic benefits for Indian smallholder farmers compared with growing the Asiatic cotton Gossypium arboreum L. Here, we compare the economic impact of growing Bt G. hirsutum with growing G. arboreum under rainfed conditions in the Indian state of Maharashtra, and show that G. arboreum can generate similar net revenue, and thus similar economic benefits for smallholder farmers compared with growing Bt G. hirsutum. We also compare the economic impact of growing Bt G. hirsutum under rainfed conditions with growing Bt G. hirsutum under irrigated conditions and show that even though Bt G. hirsutum yields increase with irrigation, the net revenue does not significantly increase because farmers using irrigation spend significantly more than farmers growing Bt G. hirsutum without irrigation. We conclude that our data provide a broader insight into how socio-economic data needs to be incorporated into agro ecological data when planning strategies to improve cotton farming in India. PMID- 27250008 TI - The gibberellin precursor GA12 acts as a long-distance growth signal in Arabidopsis. AB - The gibberellin (GA) phytohormones play important roles in plant growth and development, promoting seed germination, elongation growth and reproductive development(1). Over the years, substantial progress has been made in understanding the regulation of GA signalling and metabolism, which ensures appropriate levels of GAs for growth and development(2). Moreover, an additional level of regulation may reside in the transport of GAs from production sites to recipient tissues that require GAs for growth. Although there is considerable evidence suggesting the existence of short- and long-distance movement of GAs in plants(3-8), the nature and the biological properties of this transport are not yet understood. Here, we combine biochemical and conventional micrografting experiments in Arabidopsis thaliana to show that the GA precursor GA12, although biologically inactive by itself, is the major mobile GA signal over long distances. Quantitative analysis of endogenous GAs in xylem and phloem exudates further indicates that GA12 moves through the plant vascular system. Finally, we demonstrate that GA12 is functional in recipient tissues, supporting growth via the activation of the GA signalling cascade. Collectively, these results reveal the existence of long-range transport of endogenous GA12 in plants that may have implications for the control of developmental phase transitions and the adaptation to adverse environments. PMID- 27250009 TI - Chloroplasts play a central role in plant defence and are targeted by pathogen effectors. AB - Microbe associated molecular pattern (MAMP) receptors in plants recognize MAMPs and activate basal defences; however a complete understanding of the molecular and physiological mechanisms conferring immunity remains elusive. Pathogens suppress active defence in plants through the combined action of effector proteins. Here we show that the chloroplast is a key component of early immune responses. MAMP perception triggers the rapid, large-scale suppression of nuclear encoded chloroplast-targeted genes (NECGs). Virulent Pseudomonas syringae effectors reprogramme NECG expression in Arabidopsis, target the chloroplast and inhibit photosynthetic CO2 assimilation through disruption of photosystem II. This activity prevents a chloroplastic reactive oxygen burst. These physiological changes precede bacterial multiplication and coincide with pathogen-induced abscisic acid (ABA) accumulation. MAMP pretreatment protects chloroplasts from effector manipulation, whereas application of ABA or the inhibitor of photosynthetic electron transport, DCMU, abolishes the MAMP-induced chloroplastic reactive oxygen burst, and enhances growth of a P. syringae hrpA mutant that fails to secrete effectors. PMID- 27250011 TI - MicroRNA transcription and processing: Elongator caught in the act. PMID- 27250012 TI - Domestication: Sweet! A naturally transgenic crop. PMID- 27250010 TI - Transcription and processing of primary microRNAs are coupled by Elongator complex in Arabidopsis. AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs that play important regulatory roles in gene expression in plants and animals. The biogenesis of miRNAs involves the transcription of primary miRNAs (pri-miRNAs) by RNA polymerase II (RNAPII) and subsequent processing by Dicer or Dicer-like (DCL) proteins. Here we show that the Elongator complex is involved in miRNA biogenesis in Arabidopsis. Disruption of Elongator reduces RNAPII occupancy at miRNA loci and pri-miRNA transcription. We also show that Elongator interacts with the DCL1 containing Dicing complex and lack of Elongator impairs DCL1 localization in the nuclear Dicing body. Finally, we show that pri-miRNA transcripts as well as DCL1 associate with the chromatin of miRNA genes and the chromatin association of DCL1 is compromised in the absence of Elongator. Our results suggest that Elongator functions in both transcription and processing of pri-miRNAs and probably couples these two processes. PMID- 27250013 TI - Expanding the role of botanical gardens in the future of food. PMID- 27250014 TI - Immune responses: Photosynthetic defence. PMID- 27250015 TI - Flower development: Compounding a raceme. PMID- 27250016 TI - Root development: Subterranean specialization. PMID- 27250017 TI - Ecology: Grassland growth. PMID- 27250019 TI - More than naming of parts. PMID- 27250018 TI - Immunity: Antagonistic acetylases. PMID- 27250021 TI - Simultaneous identification of multi-combustion-intermediates of alkanol-air flames by femtosecond filament excitation for combustion sensing. AB - Laser filamentation produced by the propagation of intense laser pulses in flames is opening up new possibility in application to combustion diagnostics that can provide useful information on understanding combustion processes, enhancing combustion efficiency and reducing pollutant products. Here we present simultaneous identification of multiple combustion intermediates by femtosecond filament excitation for five alkanol-air flames fueled by methanol, ethanol, n propanol, n-butanol, and n-pentanol. We experimentally demonstrate that the intensities of filament-induced photoemission signals from the combustion intermediates C, C2, CH, CN increase with the increasing number of carbons in the fuel molecules, and the signal ratios between the intermediates (CH/C, CH/C2, CN/C, CH/C2, CN/CH) are different for different alkanol combustion flames. Our observation provides a way for sensing multiple combustion components by femtosecond filament excitation in various combustion conditions that strongly depend on the fuel species. PMID- 27250022 TI - Monitoring of tissue optical properties during thermal coagulation of ex vivo tissues. AB - BACKGROUND AND OBJECTIVE: Real-time monitoring of tissue status during thermal ablation of tumors is critical to ensure complete destruction of tumor mass, while avoiding tissue charring and excessive damage to normal tissues. Currently, magnetic resonance thermometry (MRT), along with magnetic resonance imaging (MRI), is the most commonly used technique for monitoring and assessing thermal ablation process in soft tissues. MRT/MRI is very expensive, bulky, and often subject to motion artifacts. On the other hand, light propagation within tissue is sensitive to changes in tissue microstructure and physiology which could be used to directly quantify the extent of tissue damage. Furthermore, optical monitoring can be a portable, and cost-effective alternative for monitoring a thermal ablation process. The main objective of this study, is to establish a correlation between changes in tissue optical properties and the status of tissue coagulation/damage during heating of ex vivo tissues. MATERIALS AND METHODS: A portable diffuse reflectance spectroscopy system and a side-firing fiber-optic probe were developed to study the absorption (MUa (lambda)), and reduced scattering coefficients (MU's (lambda)) of native and coagulated ex vivo porcine, and chicken breast tissues. In the first experiment, both porcine and chicken breast tissues were heated at discrete temperature points between 24 and 140 degrees C for 2 minutes. Diffuse reflectance spectra (430-630 nm) of native and coagulated tissues were recorded prior to, and post heating. In a second experiment, porcine tissue samples were heated at 70 degrees C and diffuse reflectance spectra were recorded continuously during heating. The MUa (lambda) and MU's (lambda) of the tissues were extracted from the measured diffuse reflectance spectra using an inverse Monte-Carlo model of diffuse reflectance. Tissue heating was stopped when the wavelength-averaged scattering plateaued. RESULTS: The wavelength-averaged optical properties, and , for native porcine tissues (n = 66) at room temperature, were 5.4 +/- 0.3 cm(-1) and 0.780 +/- 0.008 cm(-1) (SD), respectively. The and for native chicken breast tissues (n = 66) at room temperature, were 2.69 +/- 0.08 cm(-1) and 0.29 +/- 0.01 cm(-1) (SD), respectively. In the first experiment, the of coagulated porcine and chicken breast tissue rose to 56.4 +/- 3.6 cm(-1) at 68.7 +/- 1.7 degrees C (SD), and 52.8 +/- 1 cm(-1) at 57.1 +/- 1.5 degrees C (SD), respectively. Correspondingly, the of coagulated porcine (140.6 degrees C), and chicken breast tissues (130 degrees C) were 0.75 +/- 0.05 cm(-1) and 0.263 +/- 0.004 cm(-1) (SD). For both tissues, charring was observed at temperatures above 80 degrees C. During continuous monitoring of porcine tissue (with connective tissues) heating, the started to rise rapidly from 13.7 +/- 1.5 minutes and plateaued at 19 +/- 2.5 (SD) minutes. The plateaued at 11.7 +/- 3 (SD) minutes for porcine tissue devoid of connective tissue between probe and tissue surface. No charring was observed during continuous monitoring of thermal ablation process. CONCLUSION: The changes in optical absorption and scattering properties can be continuously quantified, which could be used as a diagnostic biomarker for assessing tissue coagulation/damage during thermal ablation. Lasers Surg. Med. 48:686-694, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27250024 TI - Fibronectin on circulating extracellular vesicles as a liquid biopsy to detect breast cancer. AB - Extracellular vesicles (EVs) secreted from cancer cells have potential for generating cancer biomarker signatures. Fibronectin (FN) was selected as a biomarker candidate, due to the presence in surface on EVs secreted from human breast cancer cell lines. A subsequent study used two types of enzyme-linked immunosorbent assays (ELISA) to determine the presence of these proteins in plasma samples from disease-free individuals (n=70), patients with BC (n=240), BC patients after surgical resection (n=40), patients with benign breast tumor (n=55), and patients with non-cancerous diseases (thyroiditis, gastritis, hepatitis B, and rheumatoid arthritis; n=80). FN levels were significantly elevated (p< .0001) at all stages of BC, and returned to normal after tumor removal. The diagnostic accuracy for FN detection in extracellular vesicles (ELISA method 1) (area under the curve, 0.81; 95% CI, 0.76 to 0.86; sensitivity of 65.1% and specificity of 83.2%) were also better than those for FN detection in the plasma (ELISA method 2) (area under the curve, 0.77; 95% CI, 0.72 to 0.83; sensitivity of 69.2% and specificity of 73.3%) in BC. The diagnostic accuracy of plasma FN was similar in both the early-stage BC and all BC patients, as well as in the two sets. This liquid biopsy to detect FN on circulating EVs could be a promising method to detect early breast cancer. PMID- 27250023 TI - Mitochondrial oxidative phosphorylation controls cancer cell's life and death decisions upon exposure to MAPK inhibitors. AB - Although MAPK pathway inhibitors are becoming a promising anticancer strategy, they are insufficient to fully eliminate cancer cells and their long-term efficacy is strikingly limited in patients with BRAF-mutant melanomas. It is well established that BRAF inhibitors (BRAFi) hamper glucose uptake before the apparition of cell death. Here, we show that BRAFi induce an extensive restructuring of mitochondria including an increase in mitochondrial activity and biogenesis associated with mitochondrial network remodeling. Furthermore, we report a close interaction between ER and mitochondria in melanoma exposed to BRAFi. This physical connection facilitates mitochondrial Ca2+ uptake after its release from the ER. Interestingly, Mfn2 silencing disrupts the ER-mitochondria interface, intensifies ER stress and exacerbates ER stress-induced apoptosis in cells exposed to BRAFi in vitro and in vivo. This mitochondrial control of ER stress-mediated cell death is similar in both BRAF- and NRAS-mutant melanoma cells exposed to MEK inhibitors. This evidence reinforces the relevance in combining MAPK pathway inhibitors with mitochondriotropic drugs to improve targeted therapies. PMID- 27250025 TI - RIC versus MAC UCBT in adults with AML: A report from Eurocord, the ALWP and the CTIWP of the EBMT. AB - Nonrelapse mortality (NRM) is the first cause of treatment failure after unrelated cord blood transplantation (UCBT) following myeloablative conditioning (MAC). In the last decade, reduced-intensity conditioning (RIC) regimens have been developed with the aim of reducing NRM and allowing older patients and those with medical comorbidities to benefit from UCBT. The aim of the current retrospective study was to compare transplantation outcomes of acute myeloid leukemia (AML) patients given UCBT after either RIC or MAC. Data from 894 adults with AML receiving a single or double UCBT as first allograft from 2004 to 2013 at EBMT centers were included in this study. 415 patients were given UCBT after RIC while 479 patients following a MAC. In comparison to MAC recipients, RIC recipients had a similar incidence of neutrophil engraftment and of acute and chronic graft-versus-host disease (GVHD). However, RIC recipients had a higher incidence of disease relapse and a lower NRM, translating to comparable leukemia free (LFS), GVHD-free, relapse-free survival (GRFS) and overall survival (OS). These observations remained qualitatively similar after adjusting for differences between groups in multivariate analyses. In conclusion, these data suggest that LFS and OS are similar with RIC or with MAC in adults AML patients transplanted with UCBT. These observations could serve as basis for a future prospective randomized study. PMID- 27250026 TI - Functional and prognostic significance of long non-coding RNA MALAT1 as a metastasis driver in ER negative lymph node negative breast cancer. AB - MALAT1 (metastasis associated lung adenocarcinoma transcript1) is a conserved long non-coding RNA, known to regulate gene expression by modulating transcription and post-transcriptional pre-mRNA processing of a large number of genes. MALAT1 expression is deregulated in various tumors, including breast cancer. However, the significance of such abnormal expression is yet to be fully understood. In this study, we demonstrate that regulation of aggressive breast cancer cell traits by MALAT1 is not predicted solely based on an elevated expression level but is context specific. By performing loss- and gain-of function studies, both under in vitro and in vivo conditions, we demonstrate that MALAT1 facilitates cell proliferation, tumor progression and metastasis of triple negative breast cancer (TNBC) cells despite having a comparatively lower expression level than ER or HER2-positive breast cancer cells. Furthermore, MALAT1 regulates the expression of several cancer metastasis-related genes, but displays molecular subtype specific correlations with such genes. Assessment of the prognostic significance of MALAT1 in human breast cancer (n=1992) revealed elevated MALAT1 expression was associated with decreased disease-specific survival in ER negative, lymph node negative patients of the HER2 and TNBC molecular subtypes. Multivariable analysis confirmed MALAT1 to have independent prognostic significance in the TNBC lymph node negative patient subset (HR=2.64, 95%CI 1.35- 5.16, p=0.005). We propose that the functional significance of MALAT1 as a metastasis driver and its potential use as a prognostic marker is most promising for those patients diagnosed with ER negative, lymph node negative breast cancer who might otherwise mistakenly be stratified to have low recurrence risk. PMID- 27250027 TI - A novel peptide targeting Clec9a on dendritic cell for cancer immunotherapy. AB - Dendritic cells (DCs) are professional antigen-presenting cells with antigen recognition molecules on the surface. Clec9a is selectively expressed on mouse CD8a+ DCs and CD103+ DCs subsets, which are functionally similar to human BDCA3+ DCs. It is reported that Clec9a is responsible for the antigen cross-presentation of these DC subsets. In the present study, by using phage display technique, we discovered a novel peptide WH, which can selectively bind to mouse Flt3L induced Clec9a+ DCs or Clec9a over-expressed HEK-293T cells. Furthermore, by using computer-aided docking model and mutation assay, we observed that Asp248 and Trp250 are two key residues for Clec9a to bind with peptide WH. When coupled with OVA257-264 epitope, peptide WH can significantly enhance the ability of Clec9a+ DCs to activate OVA-specific CD8+ T cells, which elicit strong ability to secret IFN-gamma, express perforin and granzyme B mRNA. In B16-OVA lung metastasis mouse model, WH-OVA257-264 fusion peptide can also enhance the activation of CD8+ T cells and decrease the lung metastasis loci. All these results suggested that peptide WH could be considered as an antigen delivery carrier targeting Clec9a+ DCs for cancer immunotherapy. PMID- 27250028 TI - Transcriptomic and proteomic analysis of mouse radiation-induced acute myeloid leukaemia (AML). AB - A combined transcriptome and proteome analysis of mouse radiation-induced AMLs using two primary AMLs, cell lines from these primaries, another cell line and its in vivo passage is reported. Compared to haematopoietic progenitor and stem cells (HPSC), over 5000 transcriptome alterations were identified, 2600 present in all materials. 55 and 3 alterations were detected in the proteomes of the cell lines and primary/in vivo passage material respectively, with one common to all materials. In cell lines, approximately 50% of the transcriptome changes are related to adaptation to cell culture, and in the proteome this proportion was higher. An AML 'signature' of 17 genes/proteins commonly deregulated in primary AMLs and cell lines compared to HPSCs was identified and validated using human AML transcriptome data. This also distinguishes primary AMLs from cell lines and includes proteins such as Coronin 1, pontin/RUVBL1 and Myeloperoxidase commonly implicated in human AML. C-Myc was identified as having a key role in radiation leukaemogenesis. These data identify novel candidates relevant to mouse radiation AML pathogenesis, and confirm that pathways of leukaemogenesis in the mouse and human share substantial commonality. PMID- 27250029 TI - Genetic polymorphisms in TNIP1 increase the risk of gastric carcinoma. AB - The distribution and levels of TNIP1 in malignant and normal gastric mucosa are different, but it is not known whether TNIP1 polymorphisms are related to gastric carcinogenesis. To assess the association between four TNIP1 SNPs (rs3792792, rs4958881, rs7708392, rs10036748) and carcinogenesis, we used Sequenom Mass-ARRAY technology to determine the genotypes of 302 gastric carcinoma patients and 300 healthy controls in a Northwest Chinese Han population. These data were then compared using the Chi-square test/Fisher's exact test, genetic model analysis, and haplotype analysis. Odds ratios (OR) and 95% confidence intervals (CI) were used to evaluate the correlation. We observed that patients with the "G" allele of rs7708392 and the "C" allele of rs10036748 showed an increased risk of gastric carcinoma (OR= 1.335, 95%CI: 1.021-1.745, P= 0.035; OR= 1.358, 95%CI: 1.039 1.774, P= 0.025, respectively). Conversely, the haplotype "CT" of TNIP1 (rs7708392-rs10036748) may act as a genetic protective factor for gastric carcinoma (adjusted OR= 0.731, 95%CI: 0.552-0.970, P= 0.030). Our results are the first to suggest that genetic variation in TNIP1 gene is associated with gastric carcinoma, though, this finding must be confirmed in other populations with larger sample size. PMID- 27250030 TI - The associations between serum biomarkers and stenosis of the coronary arteries. AB - Serum biochemical indices reflect dynamic physiological and pathophysiological processes within the body, the associations between these markers and the number of stenotic coronary arteries have been rarely studied. 627 healthy controls and 1,049 coronary heart disease (CHD) patients were sequentially recruited in our hospital. The association patterns between serum biochemical markers and the numbers of stenotic coronary arteries were evaluated in a cross-sectional manner. Upon binary multiple logistic regression analysis, the risk factor patterns differed by gender. Age, high-density lipoprotein cholesterol (HDL) and homocysteine (HCY) were common risk factors for CHD in both males and females. Upon ordinal multiple logistic regression analysis, age, low-density lipoprotein cholesterol (LDL) and lipoprotein (Lp) (a) increased, and HDL decreased, as the number of stenotic coronary arteries increased in male patients. Age and Lp(a) were positively associated with the number of stenotic coronary arteries and total bilirubin (TBil) was negatively associated with the number of stenotic coronary arteries in female patients. Age and Lp(a) were common risk factors positively associated with the number of stenotic coronary arteries in both male and female patients. HDL and LDL were male-specific risk factors and TBil was a female-specific risk factor for an increasing number of stenotic coronary arteries. In conclusion, serum biomarker levels correlated with the number of stenotic coronary arteries and showed gender different patterns. PMID- 27250031 TI - CRISPR/Cas9 therapeutics: a cure for cancer and other genetic diseases. AB - Cancer is caused by a series of alterations in genome and epigenome mostly resulting in activation of oncogenes or inactivation of cancer suppressor genes. Genetic engineering has become pivotal in the treatment of cancer and other genetic diseases, especially the formerly-niche use of clustered regularly interspaced short palindromic repeats (CRISPR) associated with Cas9. In defining its superior use, we have followed the recent advances that have been made in producing CRISPR/Cas9 as a therapy of choice. We also provide important genetic mutations where CRISPRs can be repurposed to create adaptive immunity to fight carcinomas and edit genetic mutations causing it. Meanwhile, challenges to CRISPR technology are also discussed with emphasis on ability of pathogens to evolve against CRISPRs. We follow the recent developments on the function of CRISPRs with different carriers which can efficiently deliver it to target cells; furthermore, analogous technologies are also discussed along CRISPRs, including zinc-finger nuclease (ZFN) and transcription activator-like effector nucleases (TALENs). Moreover, progress in clinical applications of CRISPR therapeutics is reviewed; in effect, patients can have lower morbidity and/or mortality from the therapeutic method with least possible side-effects. PMID- 27250032 TI - Prognostic value of the autophagy markers LC3 and p62/SQSTM1 in early-stage non small cell lung cancer. AB - Autophagy is a cellular degrading process that promotes tumor cell survival or cell death in cancer, depending on the progress of oncogenesis. Protein light chain 3 (LC3) and p62/SQSTM1 (p62) are associated with autophagosomal membranes that engulf cytoplasmic content for subsequent degradation. We studied LC3 and p62 expression using immunohistochemistry in a large cohort of 466 stage I/II non small cell lung cancer (NSCLC) using a tissue microarray. We evaluated dot-like cytoplasmic expression of LC3 and dot-like, cytoplasmic and nuclear staining for p62 in relation to clinico-pathological parameters.LC3 expression correlated with all p62 patterns, as those correlated among each other (p < 0.001 each). There was no correlation with stage, age or gender. A combination of high LC3/high p62 dot-like staining (suggesting impaired autophagy) showed a trend for better outcome (p = 0.11). Interestingly, a combined low cytoplasmic/low nuclear p62 expression regardless of dot-like staining was an independent prognostic factor for longer survival (p = 0.006; HR=1.96), in addition to tumor stage (p = 0.004; HR=1.4).The autophagy markers LC3 and p62 are differentially expressed in NSCLC, pointing towards a biologically significant role. High LC3 levels seem to be linked to lower tumor aggressiveness, while high general p62 expression was significantly associated with aggressive tumor behavior. PMID- 27250033 TI - Caspase-8 inhibition represses initial human monocyte activation in septic shock model. AB - In septic patients, the onset of septic shock occurs due to the over-activation of monocytes. We tested the therapeutic potential of directly targeting innate immune cell activation to limit the cytokine storm and downstream phases. We initially investigated whether caspase-8 could be an appropriate target given it has recently been shown to be involved in microglial activation. We found that LPS caused a mild increase in caspase-8 activity and that the caspase-8 inhibitor IETD-fmk partially decreased monocyte activation. Furthermore, caspase-8 inhibition induced necroptotic cell death of activated monocytes. Despite inducing necroptosis, caspase-8 inhibition reduced LPS-induced expression and release of IL-1beta and IL-10. Thus, blocking monocyte activation has positive effects on both the pro and anti-inflammatory phases of septic shock. We also found that in primary mouse monocytes, caspase-8 inhibition did not reduce LPS induced activation or induce necroptosis. On the other hand, broad caspase inhibitors, which have already been shown to improve survival in mouse models of sepsis, achieved both. Thus, given that monocyte activation can be regulated in humans via the inhibition of a single caspase, we propose that the therapeutic use of caspase-8 inhibitors could represent a more selective alternative that blocks both phases of septic shock at the source. PMID- 27250034 TI - Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas. AB - Esophageal adenocarcinomas (EAC) are aggressive tumors with considerable rates of chemoresistance. Autophagy is a lysosome-dependent degradation process, characterized by the formation of vesicles called autophagosomes, and has been implicated in cancer. Protein light chain 3 B (LC3B) and p62 are associated with autophagosomal membranes and degraded. We aimed to assess the impact of basal autophagy on EAC. In EAC cell lines, an increase in LC3B and p62 was observed with increasing concentrations of the autophagy inhibitor chloroquine, which indicates functional basal autophagy. LC3B and p62 immunohistochemistry was performed on primary resected EAC. High LC3B and p62 expression was associated with earlier tumor stages (p < 0.05). High nuclear and cytoplasmic p62 staining were associated with a better prognosis (p = 0.006; p = 0.028). Various combinations of p62 expression with or without LC3B expression identified different prognostic groups. Tumors with low total p62 (p = 0.007) or low LC3B/low p62 expression had the worst outcome (p = 0.007; p = 0.005). A combination score of dot-like/cytoplasmic p62 and nuclear p62 staining was an independent prognostic parameter (p = 0.033; HR = 0.6). This study highlights the potential significance of basal autophagy in EAC biology. Tumors with low LC3B and p62 expression show the most aggressive behavior and may be candidates for autophagy regulating therapeutics. PMID- 27250036 TI - Contribution of polymeric materials to progress in xenotransplantation of microencapsulated cells: a review. AB - Cell microencapsulation and subsequent transplantation of the microencapsulated cells require multidisciplinary approaches. Physical, chemical, biological, engineering, and medical expertise has to be combined. Several natural and synthetic polymeric materials and different technologies have been reported for the preparation of hydrogels, which are suitable to protect cells by microencapsulation. However, owing to the frequent lack of adequate characterization of the hydrogels and their components as well as incomplete description of the technology, many results of in vitro and in vivo studies appear contradictory or cannot reliably be reproduced. This review addresses the state of the art in cell microencapsulation with special focus on microencapsulated cells intended for xenotransplantation cell therapies. The choice of materials, the design and fabrication of the microspheres, as well as the conditions to be met during the cell microencapsulation process, are summarized and discussed prior to presenting research results of in vitro and in vivo studies. Overall, this review will serve to sensitize medically educated specialists for materials and technological aspects of cell microencapsulation. PMID- 27250035 TI - Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation. AB - Osterix (Osx) is an essential transcription factor involved in osteoblast differentiation and bone formation. The precise molecular mechanisms of the regulation of Osx expression are not fully understood. In the present study, we found that in cells, both endogenous and exogenous Osx protein increased after treatment with histone deacetylase inhibitors Trichostatin A and hydroxamic acid. Meanwhile, the results of immunoprecipitation indicated that Osx was an acetylated protein and that the CREB binding protein (CBP), and less efficiently p300, acetylated Osx. The interaction and colocalization of CBP and Osx were demonstrated by Co-immunoprecipitation and immunofluorescence, respectively. In addition, K307 and K312 were identified as the acetylated sites of Osx. By contrast, HDAC4, a histone deacetylase (HDAC), was observed to interact and co localize with Osx. HDAC4 was demonstrated to mediate the deacetylation of Osx. Moreover, we found that acetylation of Osx enhanced its stability, DNA binding ability and transcriptional activity. Finally, we demonstrated that acetylation of Osx was required for the osteogenic differentiation of C2C12 cells. Taken together, our results provide evidence that CBP-mediated acetylation and HDAC4 mediated deacetylation have critical roles in the modification of Osx, and thus are important in osteoblast differentiation. PMID- 27250037 TI - How variation between individuals affects species coexistence. AB - Although the effects of variation between individuals within species are traditionally ignored in studies of species coexistence, the magnitude of intraspecific variation in nature is forcing ecologists to reconsider. Compelling intuitive arguments suggest that individual variation may provide a previously unrecognised route to diversity maintenance by blurring species-level competitive differences or substituting for species-level niche differences. These arguments, which are motivating a large body of empirical work, have rarely been evaluated with quantitative theory. Here we incorporate intraspecific variation into a common model of competition and identify three pathways by which this variation affects coexistence: (1) changes in competitive dynamics because of nonlinear averaging, (2) changes in species' mean interaction strengths because of variation in underlying traits (also via nonlinear averaging) and (3) effects on stochastic demography. As a consequence of the first two mechanisms, we find that intraspecific variation in competitive ability increases the dominance of superior competitors, and intraspecific niche variation reduces species-level niche differentiation, both of which make coexistence more difficult. In addition, individual variation can exacerbate the effects of demographic stochasticity, and this further destabilises coexistence. Our work provides a theoretical foundation for emerging empirical interests in the effects of intraspecific variation on species diversity. PMID- 27250038 TI - Hemostatic properties and protein expression profile of therapeutic apheresis plasma treated with amotosalen and ultraviolet A for pathogen inactivation. AB - BACKGROUND: The INTERCEPT Blood System (IBS) using amotosalen-HCl and ultraviolet (UV)A inactivates a large spectrum of microbial pathogens and white blood cells in therapeutic plasma. Our aim was to evaluate to what extent IBS modifies the capacity of plasma to generate thrombin and induces qualitative or quantitative modifications of plasma proteins. STUDY DESIGN AND METHODS: Plasma units from four donors were collected by apheresis. Samples were taken before (control [CTRL]) and after IBS treatment and stored at -80 degrees C until use. The activities of plasma coagulation factors and inhibitors and the thrombin generation potential were determined using assays measuring clotting times and the calibrated automated thrombogram (CAT), respectively. The proteomic profile of plasma proteins was examined using a two-dimensional differential in-gel electrophoresis (2D-DIGE) method. RESULTS: Nearly all of the procoagulant and antithrombotic factors tested retained at least 78% of their initial pre-IBS activity. Only FVII and FVIII displayed a lower level of conservation (67%), which nevertheless remained within the reference range for conventional plasma coagulation factors. The thrombin generation profile of plasma was conserved after IBS treatment. Among the 1331 protein spots revealed by 2D-DIGE analysis, only four were differentially expressed in IBS plasma compared to CTRL plasma and two were identified by mass spectrometric analysis as transthyretin and apolipoprotein A1. CONCLUSION: The IBS technique for plasma moderately decreases the activities of plasma coagulation factors and antithrombotic proteins, with no impact on the thrombin generation potential of plasma and very limited modifications of the proteomic profile. PMID- 27250039 TI - Climate change impacts on wildlife in a High Arctic archipelago - Svalbard, Norway. AB - The Arctic is warming more rapidly than other region on the planet, and the northern Barents Sea, including the Svalbard Archipelago, is experiencing the fastest temperature increases within the circumpolar Arctic, along with the highest rate of sea ice loss. These physical changes are affecting a broad array of resident Arctic organisms as well as some migrants that occupy the region seasonally. Herein, evidence of climate change impacts on terrestrial and marine wildlife in Svalbard is reviewed, with a focus on bird and mammal species. In the terrestrial ecosystem, increased winter air temperatures and concomitant increases in the frequency of 'rain-on-snow' events are one of the most important facets of climate change with respect to impacts on flora and fauna. Winter rain creates ice that blocks access to food for herbivores and synchronizes the population dynamics of the herbivore-predator guild. In the marine ecosystem, increases in sea temperature and reductions in sea ice are influencing the entire food web. These changes are affecting the foraging and breeding ecology of most marine birds and mammals and are associated with an increase in abundance of several temperate fish, seabird and marine mammal species. Our review indicates that even though a few species are benefiting from a warming climate, most Arctic endemic species in Svalbard are experiencing negative consequences induced by the warming environment. Our review emphasizes the tight relationships between the marine and terrestrial ecosystems in this High Arctic archipelago. Detecting changes in trophic relationships within and between these ecosystems requires long-term (multidecadal) demographic, population- and ecosystem-based monitoring, the results of which are necessary to set appropriate conservation priorities in relation to climate warming. PMID- 27250040 TI - Degenerative cervical myelopathy. AB - Cervical myelopathy is the most common cause of acquired spinal cord compromise. The concept of degenerative cervical myelopathy (DCM), defined as symptomatic myelopathy associated with degenerative arthropathic changes in the spine axis, is being introduced. Given its progressive nature, treatment options have to be chosen in a timely manner. Surgical options include anterior discectomy and fusion (ACDF), anterior corpectomy and fusion (ACCF), arthroplasty (in highly select cases), posterior laminectomy with/without fusion, and laminoplasty. Indications for each should be carefully considered in individual patients. Riluzole, a sodium-glutamate antagonist, is a promising option to optimize neurologic outcomes post-surgery and is being examined in the CSM-Protect Randomized Controlled Trial. Preoperative risk assessment is mandatory for prognostication. Sagittal alignment is known to play an important role to optimize surgical outcome. Guidelines for optimal management of DCM are in process. In principle, all but the mildest cases of DCM should be offered surgery for optimal outcome. PMID- 27250043 TI - Seven days in medicine: 25-31 May. PMID- 27250041 TI - Neurological complications in adult spinal deformity surgery. AB - The number of surgeries performed for adult spinal deformity (ASD) has been increasing due to an aging population, longer life expectancy, and studies supporting an improvement in health-related quality of life scores after operative intervention. However, medical and surgical complication rates remain high, and neurological complications such as spinal cord injury and motor deficits can be especially debilitating to patients. Several independent factors potentially influence the likelihood of neurological complications including surgical approach (anterior, lateral, or posterior), use of osteotomies, thoracic hyperkyphosis, spinal region, patient characteristics, and revision surgery status. The majority of ASD surgeries are performed by a posterior approach to the thoracic and/or lumbar spine, but anterior and lateral approaches are commonly performed and are associated with unique neural complications such as femoral nerve palsy and lumbar plexus injuries. Spinal morphology, such as that of hyperkyphosis, has been reported to be a risk factor for complications in addition to three-column osteotomies, which are often utilized to correct large deformities. Additionally, revision surgeries are common in ASD and these patients are at an increased risk of procedure-related complications and nervous system injury. Patient selection, surgical technique, and use of intraoperative neuromonitoring may reduce the incidence of complications and optimize outcomes. PMID- 27250042 TI - Cervical radiculopathy. AB - Cervical radiculopathy is a common clinical scenario. Patients with radiculopathy typically present with neck pain, arm pain, or both. We review the epidemiology of cervical radiculopathy and discuss the diagnosis of this condition. This includes an overview of the pertinent findings on the patient history and physical examination. We also discuss relevant clinical syndromes that must be considered in the differential diagnosis including peripheral nerve entrapment syndromes and shoulder pathology. The natural history of cervical radiculopathy is reviewed and options for management are discussed. These options include conservative management, non-operative modalities such as physical therapy, steroid injections, and operative intervention. While the exact indications for surgical intervention have not yet been elucidated, we provide an overview of the available literature regarding indications and discuss the timing of intervention. The surgical outcomes of anterior cervical decompression and fusion (ACDF), cervical disc arthroplasty (CDA), and posterior cervical foraminotomy (PCF) are discussed. PMID- 27250044 TI - Pulmonary Hypertension and Inflammation/Infection. PMID- 27250045 TI - Efficacy and Safety of Endoscopic Gallbladder Stenting for Acute Cholecystitis in Patients with Concomitant Unresectable Cancer. AB - Objective Endoscopic gallbladder stenting (EGBS) is an alternative treatment option for high-risk surgical patients with acute cholecystitis. However, there are no reports focusing on EGBS in patients with concomitant unresectable cancer. The aim of this study was thus to evaluate EGBS in such patients. Methods Twenty two consecutive patients with acute cholecystitis and unresectable cancer were enrolled between September 2010 and December 2014. Their median age was 74.5 years (range: 51-95). Thirteen patients were men and nine were women. The primary cancers of the patients were biliary tract cancer (9), pancreas cancer (9), lung cancer (2), gastric cancer (1), and colon cancer (1). The causes of cholecystitis were calculus cholecystitis (7), obstruction by malignant tumor (13), and obstruction by fully covered stent (2). Results EGBS was successfully performed in 17 patients (77.2%). The technical success rates for calculus cholecystitis, obstruction by malignant tumor, and obstruction by fully covered stent were 85.7% (6/7), 69.2% (9/13), and 100% (2/2), respectively. No complications were observed. Percutaneous transhepatic gallbladder drainage was conducted on two patients in whom EGBS had failed and then we performed EGBS by a rendezvous approach. Of the 19 patients in whom we finally deployed EGBS, the median follow up period was 229 days (range: 14-880 days). A recurrence of acute cholecystitis occurred in three (15.7%) patients 14, 130, and 440 days after EGBS placement. The rates of recurrence of cholecystitis at one and two years were 10.5% and 18.7%, respectively. Conclusion Our study demonstrated that EGBS is a safe and effective method for acute cholecystitis in patients with concomitant unresectable cancer. PMID- 27250046 TI - Seven-year Observational Study on the Association between Glycemic Control and the New Onset of Macroangiopathy in Japanese Subjects with Type 2 Diabetes. AB - Objective To examine the association between glycemic control and the new onset of macroangiopathy in Japanese subjects with type 2 diabetes. Methods We examined seven-year follow-up data for 572 patients. We divided the subjects by the average of seven-year glycemic control based on the guidelines. First, we excluded the subjects with a past history of macroangiopathy and then examined the incidence of the new onset of macroangiopathy. Results The incidence of ischemic heart disease (IHD) was 1.0% per year, and that of cerebral vascular disease (CVD) was 1.0% per year. However, IHD events were not observed at all for five years in the most intensive glycemic control group (HbA1c<6%). Similarly, CVD events were not observed at all for seven years in the most intensive glycemic control group (HbA1c<6%). In addition, the cumulative incidence rate of IHD tended to increase as the glycemic control became poorer (HbA1c<6%, 4.5%; 6%<=HbA1c<7%, 6.0%; 7%<=HbA1c<8%, 7.2%; HbA1c>=8%, 10.7%). Furthermore, a logistic regression analysis showed that the duration of diabetes and HbA1c level were independent risk factors contributing to the onset of IHD, but not to the onset of CVD. Conclusion This seven-year observational study showed the possible association between glycemic control and the onset of macroangiopathy in a total of 572 Japanese subjects with type 2 diabetes. PMID- 27250047 TI - Association of Waist Circumference and Body Fat Weight with Insulin Resistance in Male Subjects with Normal Body Mass Index and Normal Glucose Tolerance. AB - Objective We investigated the relationship of the waist circumference (WC) and body fat weight (BF) with insulin resistance in subjects with normal body mass index (BMI) and normal glucose tolerance (NGT) during a routine medical check-up. Methods We categorized 167 male subjects in three groups as follows: a group with normal BMI but high WC (normal-BMI/high-WC group; 22<=BMI<25 kg/m(2), waist >=85 cm; n=31), a group with normal BMI and normal WC (normal-BMI/normal-WC group, waist <85 cm; n=68), and a group with low normal BMI and normal WC (low normal BMI/normal-WC group; 18.5<=BMI<22 kg/m(2) and waist<85 cm; n=68). We measured the plasma glucose and serum insulin levels before glucose loading and after 30 and 120 minutes and calculated several indexes of insulin secretion and sensitivity. Results Subjects from the normal-BMI/high-WC group showed significantly decreased Matsuda index and increased homeostasis model assessment for insulin resistance (HOMA-IR) compared with normal-BMI/normal-WC group. Univariate regression analyses showed significant correlation of HOMA-IR with WC (r=0.39) and BF (r=0.37). Matsuda index was significantly correlated with WC (r=-0.39) and BF (r= 0.47). The multiple regression analysis showed that the BF is significantly correlated with HOMA-IR (p<0.05) and Masuda index (p<0.005) among the clinical variables and with HOMA-IR (p<0.05) and Masuda index (p<0.0001) among the anthropometric variables but not with WC in either analysis. Conclusion Decreased Matsuda index and increased HOMA-IR were observed in subjects from the normal BMI/high-WC group. Multivariate analysis showed that BF is associated with decreased Matsuda index and increased HOMA-IR and that WC is not associated with either factors. PMID- 27250048 TI - Clindamycin-induced Kidney Diseases: A Retrospective Analysis of 50 Patients. AB - Objective There are many adverse reactions due to clindamycin, but kidney diseases (acute kidney injury, AKI) are uncommon. However, in recent years, the rate of clindamycin-induced kidney diseases has increased. We analyzed 50 patients with clindamycin-induced kidney diseases retrospectively, and investigated the characteristics of these kidney diseases in order to provide a reference for rational clinical drug use and to reduce drug-induced organ damage. Methods We investigated 50 patients diagnosed with clindamycin-induced kidney diseases retrospectively at the Department of Nephrology, Shandong University Qilu Hospital, from January 2009 to December 2013. The parameters included in our study were age, sex, clinical manifestations, efficacy and prognosis. Results All patients were diagnosed with clindamycin-induced kidney diseases within 48 hours of the application of clindamycin at 1.0-2.0 g/day. The patients included 29 women and 21 men. Most of the enrolled patients were 20-59 years old. Fifty-one patients were diagnosed with AKI stage 3 upon admission. Thirty-three had episodes of gross hematuria, but fever, skin rash and eosinophilia were rare. Urine analysis revealed mild proteinuria and severe tubular dysfunction. In the majority of patients, AKI was severe and required renal replacement therapy, but renal function in all patients had recovered significantly two months after discharge. Conclusion Clindamycin-induced AKI is largely reversible and is associated with episodes of gross hematuria. Clinicians should use clindamycin rationally and reduce the incidence of adverse reactions. PMID- 27250049 TI - Clinical Impact of a Humanized CCR4 Antibody (Mogamulizumab) in 14 Patients with Aggressive Adult T-cell Leukemia-lymphoma Treated at a Single Institution During a Three-year Period (2012-2014). AB - Objective We elucidated the effectiveness of a humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), which typically has a poor outcome. Methods We retrospectively analyzed 14 patients with aggressive ATL who had been treated at our institution with weekly cycles of mogamulizumab for eight weeks from 2012-2014. Results The patients (median age: 63 years old) were classified as having acute- (n=10) or lymphoma-type (n=4) ATL. The prior treatment regimens consisted of CHOP, VCAP-AMP-VECP, DeVIC and CHASE, with an average of two courses (range: 1-4). The prior disease responses were partial remission (n=3) and progressive disease (n=11). The treatment was administered in the primary refractory setting (n=8), for relapse (n=2), or as bridging therapy before hematopoietic stem cell transplantation (n=4). The overall response rates were 64% and 43% after four and eight cycles (or after the final cycles), respectively. The median overall survival (OS), OS rate at six months and OS rate at 12 months were 66 days, 41.7% and 20.8%, respectively. All of the patients with acute-type ATL who showed a response to treatment had an early response. Notably, six of the 14 ATL patients showed somewhat prolonged survival (>100 days). However, relapse or disease progression in the peripheral blood, central nervous system, lymph nodes, skin, and/or bone occurred within a relatively short period after treatment. The adverse effects were tolerable, and included lymphopenia, cytomegalovirus infection and skin rash. Conclusion Mogamulizumab therapy resulted in an early and high remission rate and somewhat prolonged survival in patients with refractory ATL. However, the duration of remission was short, and there was early relapse and disease progression. This study may show the current impact of mogamulizumab in clinical practice. PMID- 27250050 TI - Serum D-dimer Levels Are Proportionally Associated with Left Atrial Enlargement in Patients with an Acute Ischemic Stroke due to Non-valvular Atrial Fibrillation. AB - Objective Left atrial enlargement (LAE) may predispose individuals to blood stasis in atrial fibrillation (AF), and thus play a crucial role in thrombogenesis. The D-dimer level is one of the surrogate markers for a hypercoagulable state and reflects thrombus formation in AF. Since the D-dimer level reflects hypercoagulability as well as thrombus and fibrin burdens, LAE could be associated with a D-dimer elevation. However, no studies have explored this association or which factors contribute to increases in the D-dimer levels in patients with AF. Therefore, we assessed whether the serum D-dimer levels are related to the left atrial volume index (LAVI) or other vascular risk factors and also evaluated the association between the D-dimer levels and the initial stroke severity. Methods Ninety-eight consecutive patients with an acute ischemic stroke and non-valvular AF (NVAF) who were anticoagulation-naive were enrolled, and all patients were stratified into moderate-to-severe and mild neurologic deficit groups using the National Institutes of Health Stroke Scale on admission. The association between the initial serum D-dimer levels and the LAVI was evaluated in all enrolled patients, and the serum D-dimer levels were compared between the two groups. Results The patients were classified into two groups according to the severity of the neurologic deficit. In a partial correlation coefficient analysis adjusted for confounding factors, an increase in the initial serum D-dimer levels was significantly associated with LAVI (r=0.286; p=0.027). A linear regression analysis showed that a history of peripheral artery disease was the factor most strongly associated with the serum D-dimer level (t=3.90, p<0.001), followed by LAVI (t=2.37, p=0.021) and a history of congestive heart failure (t=2.16, p=0.035). The D-dimer levels were higher in the moderate-to-severe neurologic deficit group than in the mild deficit group, but this difference was not statistically significant (4.5+/-7.1 vs. 1.6+/-2.6 mg/L, p=0.068). Conclusion The serum D-dimer levels were significantly associated with LAE in anticoagulation naive patients with an acute ischemic stroke and NVAF. PMID- 27250051 TI - A Possible Case of Hepatitis due to Hypereosinophilic Syndrome. AB - A 63-year-old Japanese man whose white blood cell count and total-bilirubin and aminotransferase levels were elevated was referred to our hospital. Computed tomography did not reveal any abnormalities, and there was no evidence of gastritis or colitis on esophagogastroduodenoscopy. Although the patient had no history of drug use or allergies, a high concentration of eosinophils (80%) was noted. A liver biopsy revealed hepatitis with eosinophilic infiltration. The patient's alanine aminotransferase and eosinophil levels improved with the administration of steroids. A second biopsy, performed 6 months later, showed the improvement of the eosinophilic infiltration. The patient was diagnosed with eosinophilic hepatitis due to the presence of hypereosinophilic syndrome without the dysfunction of other organs. PMID- 27250052 TI - Transcatheter Balloon Expandable Aortic Valve Implantation through an Aortofemoral Bypass Graft. AB - An 84-year-old woman was diagnosed with symptomatic severe aortic stenosis. She had previously undergone aortobifemoral bypass grafting (Y graft) for bilateral iliac stenosis. In view of a high surgical risk, a decision for transcatheter aortic valve implantation (TAVI) was made. An incision was made on the right limb of the Y graft and subsequently a 16 Fr e-sheath was smoothly advanced through the graft. A 23 mm balloon expandable valve was then advanced with no resistance and successfully deployed. This case highlights the feasibility of TAVI through the graft, but requires a thorough preprocedural assessment of the access route using multiple imaging modalities. PMID- 27250053 TI - Cardiac Asystole Triggered by Temporal Lobe Epilepsy with Amygdala Enlargement. AB - A 25-year-old previously healthy man was hospitalized for syncope. While standing, he suddenly lost consciousness, followed by a generalized tonic clonic seizure. An electrocardiogram demonstrated asystole. No cardiac abnormalities were detected on the echocardiogram, cardiac magnetic resonance imaging (MRI), positron emission tomography, or a coronary angiogram. An electrophysiological study showed normal sinus node and atrioventricular node function. An electroencephalogram revealed small spike waves in the fronto-temporal region. Brain MRI demonstrated a left-sided amygdala enlargement. To the best of our knowledge, this is the first case of temporal lobe epilepsy with an amygdala enlargement that induced cardiac asystole. PMID- 27250054 TI - Retroperitoneal Bleeding and Arteriovenous Fistula after Percutaneous Coronary Intervention Successfully Treated with Intravascular Ultrasound-guided Covered Stent Implantation. AB - The major puncture-site complications of the transfemoral approach are retroperitoneal bleeding (RPB), arteriovenous (AV) fistula, and arterial pseudoaneurysm. Although the management of RPB and AV fistula depends on individual cases, our experience shows that the use of a covered stent with intravascular ultrasound (IVUS) guidance can successfully manage percutaneous coronary intervention-associated RPB and AV fistula. IVUS guidance can therefore make it easy to use an optimal-size covered stent. PMID- 27250055 TI - Chronic Thromboembolic Pulmonary Hypertension Associated with Chronic Inflammation. AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension. According to previously reported studies in the pertinent literature, chronic inflammatory conditions may be implicated in the development of CTEPH. We herein describe the case of a 56-year-old woman who was diagnosed with CTEPH in association with chronic infection. The patient had experienced five episodes of pneumonia in the five years prior to the diagnosis of CTEPH. Blood tests from the previous five years of outpatient follow-up demonstrated that the C-reactive protein level was slightly elevated. This case suggests that a relationship exists between chronic inflammation and CTEPH, and furthermore, may contribute towards elucidating the pathophysiology of CTEPH. PMID- 27250057 TI - Pulmonary Metastatic Choriocarcinoma from a Burned-out Testicular Tumor. AB - A 54-year-old man was referred to our hospital because of progressive dyspnea. Chest computed tomography showed multiple nodular shadows with a peripheral ground-glass halo. His clinical condition continued to deteriorate with the development of progressive respiratory failure requiring mechanical ventilation. A histological examination of a transbronchial lung biopsy revealed choriocarcinoma. The patient died within nine days of admission. A histological examination of the right testis during an autopsy revealed a burned-out testicular tumor consisting of a teratoma and a fibrous scar. We herein report a rare case of pulmonary multiple metastatic choriocarcinoma originating from a burned-out testicular tumor. PMID- 27250056 TI - Excessive Dynamic Airway Collapse Detected Using Nondynamic CT. AB - Excessive dynamic airway collapse (EDAC) has been diagnosed using dynamic CT during inspiration and expiration. We herein report an asthma patient with EDAC that was detected incidentally using nondynamic CT. The patient presented with wheezing, cough and mild fever. Treatment for the asthma did not improve her wheeze. CT revealed tracheal narrowing and bulging of the posterior bronchial wall. The patient was diagnosed with EDAC by bronchoscopy. Her wheeze improved with continuous positive airway pressure therapy. Clinicians should be aware of the airway shape when performing nondynamic CT in refractory asthma patients because recognizing the existence of EDAC may help when deciding on the treatment strategy. PMID- 27250058 TI - Regression of a Pulmonary Arteriovenous Malformation after Acute Interstitial Nephritis. AB - A 68-year-old woman was scheduled to undergo percutaneous embolization of a pulmonary arteriovenous malformation (PAVM) to prevent a paradoxical embolic event. After contrast-enhanced computed tomography (CT) was performed to carefully evaluate the PAVM, she developed acute interstitial nephritis, which required steroid therapy. Moreover, her D-dimer level increased, which was suggestive of thrombus formation. After nine months, we noted that the affected vessels had markedly decreased in size, and the fistula had almost disappeared on unenhanced CT images. To our knowledge, this is the first case report to describe the regression of a PAVM, detected by CT, after the onset of acute interstitial nephritis. PMID- 27250059 TI - Pure Red Cell Aplasia and Autoimmune Hemolytic Anemia Sequentially Occurring in a Patient with Large Granular T-lymphocytic Leukemia. AB - Pure red cell aplasia (PRCA), a type of anemia, occurred in a 50-year-old man six weeks after a splenectomy. It was successfully controlled by ciclosporin A (CsA) treatment. However, the onset of acute autoimmune hemolytic anemia (AIHA) developed one week after the CsA had been tapered off. Fortunately, the AIHA responded well to a high-dose methylprednisolone and immunoglobulin treatment. Unexpectedly, the patient suffered from severe pulmonary infection three months after the AIHA therapy. Four months later, he completely stopped the methylprednisolone. The disease was diagnosed as large granular T-lymphocytic leukemia by T cell receptor gene rearrangement, a surface marker examination and immunohistochemical staining. To our knowledge, no similar cases have previously been reported in the literature. PMID- 27250060 TI - Cancer-related Stroke due to Mural Thrombus in the Extracranial Carotid Artery. AB - A 41-year-old man was admitted to our hospital because of a cancer-related stroke (CRS) caused by a thrombus of the extracranial carotid artery. He had undergone neoadjuvant radiochemotherapy for metastatic colorectal adenocarcinoma. The serum D-dimer values were within the normal range. We treated him with intravenous unfractionated heparin followed by warfarin. There were no recurrent stroke events over six months. The leading cause of a CRS is an embolism caused by hypercoagulopathy, mainly represented by non-bacterial thrombotic endocarditis. However, it was unusual that, in the current case, a thrombus of the extracranial carotid artery was formed with no significant residual stenosis, thus resulting in an artery-to-artery embolism. PMID- 27250061 TI - Invasive Intrasellar Plasmacytoma Mimicking Pituitary Adenoma. PMID- 27250062 TI - Orbital Inflammatory Pseudotumor Associated with Rheumatoid Arthritis. PMID- 27250063 TI - Immune Reconstitution Inflammatory Syndrome due to Cryptococcal Meningitis. PMID- 27250064 TI - Spontaneous Isolated Common Hepatic Artery Dissection. PMID- 27250065 TI - Aberrant salience network and its functional coupling with default and executive networks in minimal hepatic encephalopathy: a resting-state fMRI study. AB - The purposes of this study are to explore functional alterations in salience network (SN) and its functional coupling with default mode (DMN) and central executive (CEN) networks in minimal hepatic encephalopathy (MHE). Twenty cirrhotic patients with MHE, 23 cirrhotic patients without MHE (NHE), and 18 controls underwent resting-state fMRI and psychometric hepatic encephalopathy score (PHES) test. Independent component analysis was performed to obtain DMN (including three subsystems: anterior, inferior-posterior, and superior-posterior DMN [a/ip/spDMN]), SN, and CEN (including three subsystems: left-ventral, right ventral, and dorsal CEN [lv/rv/dCEN]). The intrinsic functional connectivity (iFC) within (intra-iFC) and between (inter-iFC and time-lagged inter-iFC) networks was measured. MHE patients showed decreased intra-iFC within aDMN, SN, lvCEN, and rvCEN; and decreased inter-iFC and time-lagged inter-iFC between SN and ipDMN/spDMN/lvCEN and increased inter-iFC and time-lagged inter-iFC between SN and aDMN, compared with controls. A progressive trend in connectivity alterations was found as the disease developed from NHE to MHE. The inter-iFC between ipDMN/spDMN and SN was significantly correlated with PHES score. In conclusion, an aberrant SN and its functional interaction with the DMN/CEN are core features of MHE that are associated with disease progression and may play an important role in neurocognitive dysfunction in MHE. PMID- 27250066 TI - Design, execution, and analysis of pooled in vitro CRISPR/Cas9 screens. AB - The recently described clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology has proven to be an exquisitely powerful and invaluable method of genetic manipulation and/or modification. As such, many researchers have realized the potential of using the CRISPR/Cas9 system as a novel screening method for the identification of important proteins in biological processes and have designed short guide RNA libraries for an in vitro screening. The seminal papers describing these libraries offer valuable information regarding methods for generating the short guide RNA libraries, creating cell lines containing these libraries, and specific details regarding the screening workflow. However, certain considerations are often overlooked that may be important when planning and performing a screen, including which CRISPR library to use and how to best analyze the resulting screen data. In this review, we offer suggestions to answer some of these questions that are not covered as deeply in the papers describing the available CRISPR libraries for an in vitro screening. PMID- 27250067 TI - Size-confined fixed-composition and composition-dependent engineered band gap alloying induces different internal structures in L-cysteine-capped alloyed quaternary CdZnTeS quantum dots. AB - The development of alloyed quantum dot (QD) nanocrystals with attractive optical properties for a wide array of chemical and biological applications is a growing research field. In this work, size-tunable engineered band gap composition dependent alloying and fixed-composition alloying were employed to fabricate new L-cysteine-capped alloyed quaternary CdZnTeS QDs exhibiting different internal structures. Lattice parameters simulated based on powder X-ray diffraction (PXRD) revealed the internal structure of the composition-dependent alloyed CdxZnyTeS QDs to have a gradient nature, whereas the fixed-composition alloyed QDs exhibited a homogenous internal structure. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis confirmed the size-confined nature and monodispersity of the alloyed nanocrystals. The zeta potential values were within the accepted range of colloidal stability. Circular dichroism (CD) analysis showed that the surface-capped L-cysteine ligand induced electronic and conformational chiroptical changes in the alloyed nanocrystals. The photoluminescence (PL) quantum yield (QY) values of the gradient alloyed QDs were 27-61%, whereas for the homogenous alloyed QDs, the PL QY values were spectacularly high (72-93%). Our work demonstrates that engineered fixed alloying produces homogenous QD nanocrystals with higher PL QY than composition-dependent alloying. PMID- 27250069 TI - Risk Versus Reward. PMID- 27250068 TI - Attitudes Toward Autism Spectrum Disorders Among Students of Allied Health Professions. AB - The prevalence of autism has increased dramatically. The objectives of this study were to explore attitudes toward prenatal diagnosis to detect autism prenatally and avoid having an affected child and to understand social acceptability of these disorders among students of allied health professions. In this study, college students of nursing and health systems management answered a structured self-report questionnaire (n = 305). The first part addressed the respondent's personal data. The second part targeted the respondent's attitudes toward prenatal diagnosis of non-life-threatening disorders, including autism spectrum disorders. We found that almost two thirds of the students responded that they would not proceed with a pregnancy if the child were diagnosed with autism, and more than half thought that they would not continue with a pregnancy if the fetus were diagnosed with Asperger's. Age, level of religiosity, and years of education were influential. This study is limited in scope; however, the positive attitude of the students toward prenatal diagnosis to avoid having an affected child might also reflect a negative view of autism spectrum disorders in future health care professionals. Further research of attitudes and the social acceptability of autism spectrum disorders, particularly among health care professionals, is required. PMID- 27250070 TI - Avoiding Medication Errors: Reducing Harm in Residents Using Oral Anticoagulants. AB - Medication errors involving oral anticoagulants have led to serious adverse events, including hemorrhage, treatment failures leading to thromboembolic events, and death. This article will highlight medication errors that may arise during the use of oral anticoagulants and provide risk-reduction strategies to address the potential for error and patient harm. PMID- 27250072 TI - Valproic Acid Suppositories for Management of Seizures for Geriatric Patients. AB - This case describes the use of valproic acid suppositories for secondary seizure prophylaxis in a geriatric veteran with a feeding and swallowing disorder. The effectiveness of valproic acid suppositories is outlined to reinforce the need for compounding pharmacies to have this formulation available to meet the needs of geriatric patients. PMID- 27250073 TI - Fidget Blankets: A Sensory Stimulation Outreach Program. AB - Behavioral and Psychological Symptoms of Dementia (BPSD) include behaviors such as aberrant motor behavior, agitation, anxiety, apathy, delusions, depression, disinhibition, elation, hallucinations, irritability, and sleep or appetite changes. A student-led project to provide sensory stimulation in the form of "fidget blankets" developed into a community outreach program. The goal was to decrease the use of antipsychotics used for BPSD. PMID- 27250074 TI - Help Me Remember My Meds. AB - Nonadherence has led to increased health consequences and higher health care costs. A study surveyed subjects using either blister pack or a Philips Medication Dispenser machine to determine medication adherence. Although there is still a research gap associated with medication packaging, it has great potential to help patients who have difficulty managing their multiple medications. PMID- 27250075 TI - Validating the Medication Risk Questionnaire with Family Caregivers of Older Adults. AB - This study supports the validity of the 8-item version of the Medication-Risk Questionnaire (MRQ8). The MRQ8 can identify higher-risk patients via family caregivers and target them for medication review and other preventive intervention. It also enables pharmacists to collaborate with family caregivers in identifying older adults at high risk for medication-related problems. PMID- 27250076 TI - The Medicare Advisory Commission. PMID- 27250077 TI - Key genes and pathways predicted in papillary thyroid carcinoma based on bioinformatics analysis. AB - PURPOSE: The aim of this study was to predict the key genes and pathways associated with papillary thyroid carcinoma (PTC). METHODS: Based on the microarray data of GSE3467 from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between 9 PTC samples and 9 normal controls. With the identified DEGs, functional enrichment analyses were performed. Additionally, a protein-protein interaction network was constructed to screened out some key gene nodes. These key nodes were then performed clustering analysis and pathway enrichment analysis. Furthermore, human PTC-associated network was constructed based on these key genes to investigate the potential relationships between genes and PTC. RESULTS: A total of 651 up-regulated and 692 down-regulated DEGs were identified in PTC samples compared with controls. The up regulated DEGs, such as complement component 3 (C3), were mainly enriched in hsa04610:Complement and coagulation cascades. The down-regulated DEGs, including paired box 8 (PAX8), peroxisome proliferator-activated receptor gamma (PPARG), and cadherin 1, type 1 were found enriched in hsa05216:Thyroid cancer. Total 33 DEGs were considered as key genes, such as PAX8, PPARG and Jun proto-oncogene (JUN). Disease-associated network analysis found that 15 key genes such as JUN, PPARG and matrix metallopeptidase 9 (MMP9) were involved in this network. CONCLUSIONS: DEGs of C3, PPARG, PAX8, JUN and MMP9 were differentially expressed in PTC samples and may be used as potential biomarkers in the diagnosis and treatment of PTC. Additionally, pathways of complement and coagulation cascades and thyroid cancer may also play important roles in the development of PTC. PMID- 27250079 TI - Sharing Progress in Neonatal (SPIN) Lung and Brain. PMID- 27250078 TI - Management of chronic vulvovaginal candidiasis: a long term retrospective study. AB - BACKGROUND: Chronic vulvovaginal candidiasis (CVVC) is an unremitting condition causally associated with species of Candida. Limited data are available on its management and long-term outcomes. This retrospective study aimed to explore the long-term outcomes of patients who had experienced symptom remission after a course of oral antifungals. METHODS: Retrospective study conducted over 1 year from data obtained from a vulval dermatology outpatient clinic in Sydney, Australia. Data from 208 patients satisfying presumptive or definitive criteria for CVVC who had been successfully treated with oral azole antifungal medication were collected from a database, including drugs, induction and maintenance treatment regimes, results and adverse effects. RESULTS: Altogether 208 patients commenced an induction regime of oral fluconazole 50-100 mg daily for up to 12 weeks. All patients demonstrated a clinical improvement within 12 weeks. Of the 208 patients, subsequently 95% remained on oral fluconazole for maintenance treatment, 3% changed to other antifungals due to adverse effects and 2% ceased treatment. The most common maintenance regime was oral fluconazole 50 mg twice weekly (46%). Of the study cohort 99% remained on treatment with antifungal therapy for symptom suppression with the mean duration of follow up 26.2 months (range, 5 months to 8.5 years). CONCLUSIONS: Long-term symptom remission was possible in this subset of women with CVVC using fluconazole 50-100 mg or itraconazole 50-100 mg. However, most were unable to cease treatment without experiencing relapse. Adverse effects in this cohort were minimal and there were no cases of drug-induced hepatitis. PMID- 27250080 TI - Quench field sensitivity of two-particle correlation in a Hubbard model. AB - Short-range interaction can give rise to particle pairing with a short-range correlation, which may be destroyed in the presence of an external field. We study the transition between correlated and uncorrelated particle states in the framework of one- dimensional Hubbard model driven by a field. We show that the long time-scale transfer rate from an initial correlated state to final uncorrelated particle states is sensitive to the quench field strength and exhibits a periodic behavior. This process involves an irreversible energy transfer from the field to particles, leading to a quantum electrothermal effect. PMID- 27250081 TI - A rapid assessment of barriers and facilitators to safety culture in an intensive care unit. AB - The Hospital Survey on Patient Safety was used to identify opportunities for safety culture improvement in a 30-bed intensive care unit. Based on the survey results, a core team decided to focus on three safety domains: reporting errors, approachability of authority figures and handovers. The project team subsequently interviewed 39 intensive care unit staff members, gathering information on these three domains that will inform future safety efforts. Numerous barriers and facilitators to improvement were described. This mixed-methods approach could be applied in other hospitals seeking to quickly yet thoroughly understand how their safety culture can be improved. Developing local strategies to reduce these barriers may promote a safer patient experience at our hospital. PMID- 27250082 TI - The Bare Minimum: The Reality of Global Anaesthesia and Patient Safety. PMID- 27250083 TI - Efficacy of Surgical Simulation Training in a Low-Income Country. AB - INTRODUCTION: Simulation training has evolved as an important component of postgraduate surgical education and has shown to be effective in teaching procedural skills. Despite potential benefits to low- and middle-income countries (LMIC), simulation training is predominately used in high-income settings. This study evaluates the effectiveness of simulation training in one LMIC (Rwanda). METHODS: Twenty-six postgraduate surgical trainees at the University of Rwanda (Kigali, Rwanda) and Dalhousie University (Halifax, Canada) participated in the study. Participants attended one 3-hour simulation session using a high-fidelity, tissue-based model simulating the creation of an end ileostomy. Each participant was anonymously recorded completing the assigned task at three time points: prior to, immediately following, and 90 days following the simulation training. A single blinded expert reviewer assessed the performance using the Objective Structured Assessment of Technical Skill (OSATS) instrument. RESULTS: The mean OSATS score improvement for participants who completed all the assessments was 6.1 points [95 % Confidence Interval (CI) 2.2-9.9, p = 0.005]. Improvement was sustained over a 90-day period with a mean improvement of 4.1 points between the first and third attempts (95 % CI 0.3-7.9, p = 0.038). Simulation training was effective in both study sites, though most gains occurred with junior-level learners, with a mean improvement of 8.3 points (95 % CI 5.1-11.6, p < 0.001). Significant improvements were not identified for senior-level learners. CONCLUSION: This study supports the benefit for simulation in surgical training in LMICs. Skill improvements were limited to junior-level trainees. This work provides justification for investment in simulation-based curricula in Rwanda and potentially other LMICs. PMID- 27250084 TI - Distribution of natural and artificial radionuclides in chernozem soil/crop system from stationary experiments. AB - The present paper focuses on the determination of radiological characteristics of cultivated chernozem soil and crops from long-term field experiments, taking into account the importance of distribution and transfer of radionuclides in the soil plant system, especially in agricultural cropland. The investigation was performed on the experimental fields where maize, winter wheat, and rapeseed were cultivated. Analysis of radioactivity included determination of the gross alpha and beta activity as a screening method, as well as the activities of the following radionuclides: natural ((210)Pb, (235)U, (238)U, (226)Ra, (232)Th, (40)K, (7)Be) and artificial ((90)Sr and (137)Cs). The activities of natural and artificial ((137)Cs) radionuclides were determined by gamma spectrometry, while the artificial radionuclide (90)Sr was determined by a radiochemical analytical method. Based on the obtained results for the specific activity of (40)K, (137)Cs, and (90)Sr, accumulation factors for these radionuclides were calculated in order to estimate transfer of radionuclides from soil to crops. The results of performed analyses showed that there is no increase of radioactivity that could endanger the food production through the grown crops. PMID- 27250085 TI - Enhancement of sediment phosphorus release during a tunnel construction across an urban lake (Lake Donghu, China). AB - Tunnel construction in watershed area of urban lakes would accelerate eutrophication by inputting nutrients into them, while mechanisms underlying the internal phosphorus cycling as affected by construction events are scarcely studied. Focusing on two main pathways of phosphorus releasing from sediment (enzymatic mineralization and anaerobic desorption), spatial and temporal variations in phosphorus fractionation, and activities of extracellular enzymes (alkaline phosphatase, beta-1,4-glucosidase, leucine aminopeptidase, dehydrogenase, lipase) in sediment were examined, together with relevant parameters in interstitial and surface waters in a Chinese urban lake (Lake Donghu) where a subaqueous tunnel was constructed across it from October 2013 to July 2014. Higher alkaline phosphatase activity (APA) indicated phosphorus deficiency for phytoplankton, as illustrated by a significantly negative relationship between APA and concentration of dissolved total phosphorus (DTP). Noticeably, in the construction area, APAs in both sediment and surface water were significantly lower than those in other relevant basins, suggesting a phosphorus supply from some sources in this area. In parallel, its sediment gave the significantly lower iron-bound phosphorus (Fe(OOH)~P) content, coupled with significantly higher ratio of iron (II) to total iron content (Fe(2+)/TFe) and dehydrogenase activities (DHA). Contrastingly, difference in the activities of sediment hydrolases was not significant between the construction area and other basins studied. Thus, in the construction area, subsidy of bioavailable phosphorus from sediment to surface water was attributable to the anaerobic desorption of Fe(OOH)~P rather than enzymatic mineralization. Finally, there existed a significantly positive relationship between chlorophyll a concentration in surface water and Fe(OOH)~P content in sediment. In short, construction activities within lakes may interrupt cycling patterns of phosphorus across sediment-water interface by enhancing release of redox-sensitive phosphate, and thereby facilitating phytoplankton growth in water column. PMID- 27250086 TI - Seasonal variation of indoor and outdoor air quality of nitrogen dioxide in homes with gas and electric stoves. AB - Indoor air pollution significantly influences personal exposure to air pollution and increases health risks. Nitrogen dioxide (NO2) is one of the major air pollutants, and therefore it is important to properly determine indoor concentration of this pollutant considering the fact that people spend most of their time inside. The aim of this study was to assess indoor and outdoor concentration of NO2 during each season; for this purpose, passive sampling was applied. We analyzed homes with gas and electric stoves to determine and compare the concentrations of NO2 in kitchen, living room, and bedroom microenvironments (MEs). The accuracy of passive sampling was evaluated by comparing the sampling results with the data from air quality monitoring stations. The highest indoor concentration of NO2 was observed in kitchen ME during the winter period, the median concentration being 28.4 MUg m(-3). Indoor NO2 levels in homes with gas stoves were higher than outdoor levels during all seasons. The concentration of NO2 was by 2.5 times higher in kitchen MEs with gas stoves than with electric stoves. This study showed that the concentration of NO2 in indoor MEs mainly depended on the stove type used in the kitchen. Homes with gas stoves had significantly higher levels of NO2 in all indoor MEs compared with homes where electric stoves were used. PMID- 27250087 TI - Inhibition of five natural products from Chinese herbs on the growth of Chattonella marina. AB - The effects of five natural products from Chinese herbs including evodiamine, curcumin, 4-methoxysalicylaldehyde, esculin hydrate, and gramine on the growth of Chattonella marina, one of the most noxious red tide algae, were observed. Among them, gramine exhibited the highest inhibitory rate with LC50, 96h of 0.51 mg/l. After exposure to gramine, the activities of superoxide dismutase (SOD) and catalase (CAT), and content of malondialdehyde (MDA) increased in C. marina, suggesting that gramine could induce microalgae oxidative stress. In addition, chlorophyll a and the maximum quantum yield of photosynthesis (Fv/Fm) decreased following exposure to gramine, indicating the inhibition of photosynthesis activity in the microalgae. Combined with the fast inhibition against the algal cells and environmentally friendly character of gramine, we proposed that gramine might be a potential algaecide against marine harmful algae and that the oxidative damage and photosynthesis inhibition might be responsible for the toxicity of gramine on harmful algae. PMID- 27250088 TI - F sorption/desorption on two soils and on different by-products and waste materials. AB - We used batch-type experiments to study F sorption/desorption on a forest soil, a vineyard soil, pyritic material, granitic material, finely and coarsely ground mussel shell, mussel shell calcination ash, oak wood ash, pine-sawdust, slate processing fines, and three different mixtures that included three components: sewage sludge, mussel shell ash, and calcined mussel shell or pine wood ash. The three waste mixtures, forest soil, pyritic material, and shell ash showed high sorption capacity (73-91 % of added F) and low desorption, even when 100 mg F L( 1) was added. All these materials (and to a lower extent wood ash) could be useful to remove F from polluted media (as certain soils, dumping sites, and contaminated waters). The vineyard soil, the granitic material, mussel shell, slate fines, and pine-sawdust were less effective in F removal. In most cases, sorption data fitted better to the Freundlich than to the Langmuir equation. These results can be useful to program the correct management of the soils, by products, and waste materials assayed, mostly in situations where F concentrations are excessive and F removal should be promoted. PMID- 27250089 TI - Heavy metals in aquatic organisms of different trophic levels and their potential human health risk in Bohai Bay, China. AB - Fourteen aquatic organism samples were collected from Bohai Bay, and concentrations of five heavy metals were measured to evaluate the pollution levels in aquatic organisms and the potential risk to human health. The concentrations of Zn and Cu were much higher than those of Cd, Cr, and Pb in all the organisms. In general, the heavy metal concentration levels were in the order phytoplankton < zooplankton < fish < shrimp < shellfish. Heavy metal concentrations in higher trophic-level aquatic organisms in Bohai Bay were compared to those in the organisms from other worldwide coastal waters. The concentration levels of most heavy metals were higher than the 75th percentile, except that Pb concentration was between the 25th and 50th percentiles. The calculated bioconcentration factors (BCF) of Cr, Cu, and Pb for phytoplankton were less than 100, indicating no accumulation in primary producers. The bioaccumulation factor (BAF) of Pb for zooplankton was the highest, indicating significant Pb accumulation in zooplankton. For higher trophic-level aquatic organisms, the order of BAF values was fish < shrimp < shellfish for most metals except for Pb. The human health risk assessment suggests that strict abatement measures of heavy metals must be taken to decrease the health risk caused by consuming aquatic products. PMID- 27250090 TI - Genotoxic effect of a binary mixture of dicamba- and glyphosate-based commercial herbicide formulations on Rhinella arenarum (Hensel, 1867) (Anura, Bufonidae) late-stage larvae. AB - The acute toxicity of two herbicide formulations, namely, the 57.71 % dicamba (DIC)-based Banvel((r)) and the 48 % glyphosate (GLY)-based Credit((r)), alone as well as the binary mixture of these herbicides was evaluated on late-stage Rhinella arenarum larvae (stage 36) exposed under laboratory conditions. Mortality was used as an endpoint for determining acute lethal effects, whereas the single-cell gel electrophoresis (SCGE) assay was employed as genotoxic endpoint to study sublethal effects. Lethality studies revealed LC5096 h values of 358.44 and 78.18 mg L(-1) DIC and GLY for Banvel((r)) and Credit((r)), respectively. SCGE assay revealed, after exposure for 96 h to either 5 and 10 % of the Banvel((r)) LC5096 h concentration or 5 and 10 % of the Credit((r)) LC5096 h concentration, an equal significant increase of the genetic damage index (GDI) regardless of the concentration of the herbicide assayed. The binary mixtures of 5 % Banvel((r)) plus 5 % Credit((r)) LC5096 h concentrations and 10 % Banvel((r)) plus 10 % Credit((r)) LC5096 h concentrations induced equivalent significant increases in the GDI in regard to GDI values from late-stage larvae exposed only to Banvel((r)) or Credit((r)). This study represents the first experimental evidence of acute lethal and sublethal effects exerted by DIC on the species, as well as the induction of primary DNA breaks by this herbicide in amphibians. Finally, a synergistic effect of the mixture of GLY and DIC on the induction of primary DNA breaks on circulating blood cells of R. arenarum late-stage larvae could be demonstrated. PMID- 27250091 TI - Mechanism and toxicity research of benzalkonium chloride oxidation in aqueous solution by H2O2/Fe(2+) process. AB - As widely used disinfectants, the pollution caused by benzalkonium chloride (BAC) has attracted a lot of attention in recent years. Since it is not suitable for biodegradation, BAC was degraded firstly by Fenton advanced oxidation technologies (AOTs) in this research to enhance the biodegradability of the pollutions. The result revealed that the optimal molar ratio of H2O2/Fe(2+) for BAC degradation was 10:1, and the COD removal rate was 32 %. To clarify the pathway of degradation, the technique of GC-MS was implemented herein to identify intermediates and the toxicity of those BAC intermediates were also novelty tested through microbial fuel cells (MFC). The findings indicated that ten transformation products including benzyl dimethyl amine and dodecane were formed during the H2O2/Fe(2+) processes, which means the degradation pathway of BAC was initiated both on the hydrophobic (alkyl chain) and hydrophilic (benzyl and ammonium moiety) region of the surfactant. The toxicity of BAC before and after treated by Fenton process was monitored through MFC system. The electricity generation was improved 337 % after BAC was treated by H2O2/Fe(2+) oxidation processes which indicated that the toxicity of those intermediates were much lower than BAC. The mechanism and toxicity research in this paper could provide the in-depth understanding to the pathway of BAC degradation and proved the possibility of AOTs for the pretreatment of a biodegradation process. PMID- 27250092 TI - Microalga, Acutodesmus obliquus KGE 30 as a potential candidate for CO2 mitigation and biodiesel production. AB - In this study, the effect of flue gas CO2 on growth, lipid production, and fatty acid composition of a green microalga Acutodesmus obliquus KGE 30 was investigated. The highest growth rate (0.46 g L(-1) and MUmax = 1.09 day(-1)), total inorganic carbon removal (95.9 mg L(-1)), and lipid productivity (20.1 mg L(-1) day L(-1)) was obtained at 14.1 % CO2 after 4 days of cultivation. In a semicontinuous batch reactor, the highest biomass production (1.19 g L(-1)) was achieved after 12 days with continuous injection of flue gas CO2. Compared with synthetic CO2, fatty acid methyl ester analysis showed that the amount of unsaturated fatty acid increased by 19.2 % with 14.1 % flue gas CO2. The application of flue gas CO2 improved biomass production and lipid productivity in A. obliquus. The current investigation demonstrated that the use of flue gas CO2 could reduce the cost of microalgae biomass production for better biofuel generation. PMID- 27250093 TI - Variations in organic carbon, aggregation, and enzyme activities of gangue-fly ash-reconstructed soils with sludge and arbuscular mycorrhizal fungi during 6 year reclamation. AB - Mining activities can cause drastic disturbances in soil properties, which adversely affect the nutrient cycling and soil environment. As a result, many efforts have been made to explore suitable reclamation strategies that can be applied to accelerate ecology restoration. In this study, we reconstructed mine soils with fly ash, gangue, sludge, planted ryegrass, and inoculated arbuscular mycorrhizal fungi (AMF) in Pangzhuang mine of Xuzhou during 2009 to 2015. The soil aggregation process, enzyme activities (i.e., invertase, urease and acid phosphatase activities), soil organic carbon (SOC) as well as other soil nutrients such as nitrogen, phosphorus, and potassium contents of the reconstructed mine soils were monitored during 6-year reclamation. The integrated application of sludge and AMF led to a promising reclamation performance of mining areas, in which soil aggregate stability, enzyme activities, SOC, and ryegrass biomass were effectively enhanced. The micro-aggregates (< 0.25 mm) decreased with the increase of macro-aggregates (> 0.25 mm) during the reclamation, indicating that macro-aggregates were gradually formed from micro aggregates during the pedogenesis of reconstructed mine soils. The correlation analysis shows that SOC contents in aggregate fraction of 0.25~0.5 mm were correlated with aggregate distribution and enzyme activities. Enzyme activities, however, were not significantly correlated with aggregate distribution. The outcomes from the present study could enrich our understanding on soil property changes in pedogenesis process of reconstructed mine soils, and meanwhile, the employment of sludge combined with AMF is suggested to be an effective alternative for the mine soil reclamation. PMID- 27250094 TI - Evaluation of the joint toxicity of chlorpyrifos ethyl and fenobucarb on climbing perch (Anabas testudineus) from rice fields in the Mekong Delta, Vietnam. AB - Organophosphates (e.g. chlorpyrifos ethyl) and carbamates (e.g. fenobucarb) are commonly used to control a wide range of pests in rice fields of the Mekong Delta in Vietnam. This study assesses the combined effect of chlorpyrifos ethyl (CPF) and fenobucarb (F), applied at concentrations used by rice farmers, on the brain acetylcholinesterase (AChE) activity in climbing perch fingerlings from rice fields in the Mekong Delta. It also investigates if Pyridine-2-aldoxime methiodide (2-PAM) can be used to reactivate cholinesterase that has been blocked by CPF. Three days after spraying, the water concentrations of both insecticides decreased quickly below the detection levels. However, the brain AChE activity in fish was inhibited for more than 7 days. The results indicate a quicker but less prolonged inhibition of the brain AChE activity by the mixture than by only CPF. The inhibition levels were above 70 % only during the first 48 h, which could explain why all fish survived. 2-PAM resulted in a significant reactivation of the cholinesterase blocked by a combination of CPF and F, and it is proposed that the reactivation by 2-PAM could provide a way to assess the AChE inhibition levels in organisms, when no unexposed individuals are available as controls. The results indicate that the current use of CPF and F in rice farming in the Mekong Delta is likely to cause negative effects on non-target organisms. Many of these effects may be sub-lethal, and there is a need to develop biomarkers that are relevant, inexpensive and easy to apply. The results show that brain AChE in climbing perch fingerling is a relevant biomarker for monitoring of exposure to, and sub-lethal impacts from organophosphates and carbamates under tropical conditions in developing countries. PMID- 27250095 TI - Heart Failure in a Preterm Infant. Case Report and Echocardiographic Clues for the Diagnostic Approach to Pulmonary Sequestration. AB - Pulmonary sequestration is an unusual cause of heart failure in infants. We report a preterm newborn with signs of congestive heart failure supposed secondary to a ductus arteriosus that was finally diagnosed as a coexistent extralobar pulmonary sequestration. In this case, Doppler echocardiography was essential for diagnosis, revealing an abnormal systemic arterial supply to the sequestered lung and abnormal venous drainage. PMID- 27250096 TI - Survival after percutaneous coronary intervention for chronic total occlusion. AB - BACKGROUND: There is limited data on prognosis after percutaneous coronary intervention (PCI) for coronary chronic total occlusions (CTO) in the era of drug eluting stents (DES). AIMS: This study investigates the specific contribution of CTO recanalization to the survival benefit of complete revascularization. METHODS: Consecutive patients who underwent PCI of a CTO at our center between 01/2005 and 12/2013 were followed for a median of 2.6 years (interquartile range 1.1-3.1 years). All-cause mortality was compared between patients with successful and failed PCI of CTO without and with adjustment for pertinent co-variables by the Cox models. RESULTS: The study comprised 2002 patients with attempted PCI of CTO (mean age 65.2 +/- 11 years, 17 % female), 82 % had multivessel disease. The CTO PCI was successful in 1662 (83 %) patients with a DES rate of 94 %. All-cause mortality was significantly lower in patients with successful PCI of CTO compared to failed PCI of CTO (15.3 vs. 25.9 % at 4 years; P < 0.001). In the multivariable model, both successful CTO PCI and complete revascularization were strong independent predictors of reduced long-term mortality (adjusted hazard ratio (HR) 0.72; 95 % confidence interval (CI) 0.53-0.97; P = 0.03 and adjusted HR 0.59; 95 % CI 0.42-0.82; P = 0.002). Also within the subset of incomplete revascularization, successful PCI of CTO was associated with reduced mortality (adjusted HR: 0.67; 95 % CI: 0.50-0.92; P = 0.012). CONCLUSION: Successful CTO recanalization is an independent predictor for improved long-term survival. Persistent CTO lesions are associated with significantly worse survival than persistent non-occlusive coronary lesions. PMID- 27250097 TI - Assessing the sustainability of freshwater systems: A critical review of composite indicators. AB - Quantitative indicators are a common means of assessing the complex dimensions of a sustainable freshwater system, and framing scientific knowledge for policy and decision makers. There is an abundance of indicators in use, but considerable variation in terms of what is being measured and how indicators are applied, making it difficult for end-users to identify suitable assessment methods. We review 95 water-related indices and analyze them along their normative, procedural, and systemic dimensions to better understand how problems are being defined, highlight overlaps and differences, and identify the context(s) in which a particular index is useful. We also analyze the intended use, end-users, and geographic scale of application for each index. We find that risk assessment is the most common application (n = 25), with indices in this group typically focusing either on hazard identification (biophysical assessments) or vulnerability of human populations. Indices that measure freshwater ecological health are not explicitly linking these indicators to ecosystem services, and in fact the concept of ecosystem services is rarely (n = 3) used for indicator selection. Resource managers are the most common group of intended end-users (n = 25), but while 28 indices involved consultation with potential end-users, 11 did not specify an intended use. We conclude that indices can be applied as solution oriented tools, evaluating scenarios and identifying tradeoffs among services and beneficiaries, rather than only assessing and monitoring existing conditions. Finally, earlier engagement of end-users is recommended to help researchers find the right balance among indices' salience, legitimacy, and credibility and thus improve their decision relevance. PMID- 27250098 TI - Predicting the export and concentrations of organic carbon, nitrogen and phosphorus in boreal lakes by catchment characteristics and land use: A practical approach. AB - The majority of C, N and P in boreal lakes are in organic form. Organically bound nutrients are released through biodegradation or photodegradation which affects the water quality, eutrophication and greenhouse gas emissions of lakes. We tested whether open land-use data combined with land-use-specific export coefficients can be used to predict total organic carbon (TOC), dissolved organic nitrogen (DON) and dissolved organic phosphorus (DOP) loading and lake water concentrations. Using data from 12 lake catchments in eastern Finland, we found that land use and management of the catchment explained a substantial proportion of the variations in TOC (r 2 = 0.78), DON (r 2 = 0.55) and DOP (r 2 = 0.80) concentrations between lakes. The computation does not account for in-lake processes, which are reflected as mismatch between the predicted and observed concentrations. However, this simple practical approach is useful in ranking lakes according to their water quality. The results indicated that natural sources dominate TOC, DON and DOP exports; the background leachings accounted for 57-99 %, 48-96 % and 55-99 % of TOC, DON and DOP export, respectively. The proposed method has promise as a practical decision support tool for assessing the impacts of land use on water quality. The results showed that possibilities to control TOC, DON and DOP loading to surface waters are limited to catchments where the peatland proportion is low and anthropogenic sources significant. PMID- 27250099 TI - Quantity discrimination in parental fish: female convict cichlid discriminate fry shoals of different sizes. AB - Numerical abilities have been found to be adaptive in different contexts, including mating, foraging, fighting assessment and antipredator strategies. In species with parental care, another potential advantage is the possibility to adjust parental behavior in relation to the numerosity of the progeny. The finding that many fish vary their parental investment in relation to brood size advocates the existence of a mechanism for appraising offspring number, an aspect that has never been directly investigated. Here we tested the ability of parental female convict cichlid (Amatitlania nigrofasciata) to discriminate between two fry groups differing in number by measuring time spent attempting to recover groups of fry experimentally displaced from the next. Females spent more time trying to recover the fry from larger groups when tested with contrasts 6 versus 12 (1:2) and 6 versus 9 fry (2:3); however, they showed no preference in the 6 versus 8 (3:4) contrast, suggesting that this task exceeds their discrimination capacity. PMID- 27250100 TI - Translating vibrational spectroscopy into clinical applications - vision or reality? AB - The Faraday Discussion meeting "Advanced Vibrational Spectroscopy for Biomedical Applications" provided an excellent opportunity to share and discuss recent research and applications on a highly interdisciplinary level. Spectral pathology, single cell analysis, data handling, clinical spectroscopy, and the spectral analysis of biofluids were among the topics covered during the meeting. The focus on discussion rather than "merely" presentation was highly appreciated and fruitful discussions evolved around the interpretation of the amide-bands, optical resolution, the role of diffraction and data analysis procedure, to name a few. The meeting made clear that the spectroscopy of molecular vibrations in biomolecules has evolved from a purely academic research tool to a technology used in clinical practice in some cases. In this sense, biomedical vibrational spectroscopy has reached a pivotal point at which questions like diagnostic value, therapeutic consequence and financial viability are gaining more and more importance. PMID- 27250101 TI - Hypoxia and Reactive Oxygen Species Homeostasis in Mesenchymal Progenitor Cells Define a Molecular Mechanism for Fracture Nonunion. AB - Fracture nonunion is a major complication of bone fracture regeneration and repair. The molecular mechanisms that result in fracture nonunion appearance are not fully determined. We hypothesized that fracture nonunion results from the failure of hypoxia and hematoma, the primary signals in response to bone injury, to trigger Bmp2 expression by mesenchymal progenitor cells (MSCs). Using a model of nonstabilized fracture healing in transgenic 5'Bmp2BAC mice we determined that Bmp2 expression appears in close association with hypoxic tissue and hematoma during the early phases of fracture healing. In addition, BMP2 expression is induced when human periosteum explants are exposed to hypoxia ex vivo. Transient interference of hypoxia signaling in vivo with PX-12, a thioredoxin inhibitor, results in reduced Bmp2 expression, impaired fracture callus formation and atrophic-like nonunion by a HIF-1alpha independent mechanism. In isolated human periosteum-derived MSCs, BMP2 expression could be induced with the addition of platelets concentrate lysate but not with hypoxia treatment, confirming HIF 1alpha-independent BMP2 expression. Interestingly, in isolated human periosteum derived mesenchymal progenitor cells, inhibition of BMP2 expression by PX-12 is accomplished only under hypoxic conditions seemingly through dis-regulation of reactive oxygen species (ROS) levels. In conclusion, we provide evidence of a molecular mechanism of hypoxia-dependent BMP2 expression in MSCs where interference with ROS homeostasis specifies fracture nonunion-like appearance in vivo through inhibition of Bmp2 expression. Stem Cells 2016;34:2342-2353. PMID- 27250102 TI - Impact of physical exercise/activity on vascular structure and inflammation in pediatric populations: A literature review. AB - PURPOSE: To describe the effects of physical exercise/activity on the vascular architecture of children and adolescents, as well as to identify the effects of inflammation and sedentary behaviors on this relationship. METHODS: Potentially relevant articles were identified in the databases MEDLINE and PubMed covering the period from 2000 to 2015. No language restrictions were applied. RESULTS: Thirteen articles were found that included obese boys and girls in their samples (aged 9-19). Six interventional studies assessed inflammation and in five of these, physical exercise decreased inflammation. In 10 studies, vascular architecture was affected by physical exercise/activity. CONCLUSIONS: The impact of physical exercise on vascular architecture and inflammation seems relevant, but has been mainly investigated in obese groups. PRACTICAL IMPLICATIONS: Health professionals should act together in organized interventions in schools, targeting the promotion of higher physical activity levels in children and adolescents. PMID- 27250103 TI - Synthesis of benzo[a]carbazole derivatives from 3-ethylindoles by exploiting the dual character of benzoquinone as an oxidizing agent and dienophile. AB - The dual character of benzoquinone is exploited for the synthesis of benzo[a]carbazole derivatives starting from 3-ethylindole derivatives. A diene is generated in situ from the 3-ethylindole derivative with the help of benzoquinone, where it acts as an oxidizing agent. Later it serves as a dienophile and participates in a Diels-Alder reaction with the diene to afford benzo[a]carbazole derivatives. PMID- 27250104 TI - [Dermatological diseases of the external male genitalia : Part 1]. AB - The urological examination of male patients includes an inspection of the external genitalia whereby a variety of dermatological alterations can be found. Not all dermatological findings are of clinical relevance. Pearly penile papules and heterotopic sebaceous glands are examples of normal physiological variations. Most penile melanotic macules, angiokeratomas, fibromas and angiomas do not have to be treated; however, penile skin lesions may also be symptoms of other diseases, such as circinate balanitis in Reiter's syndrome and multiple angiokeratomas in Fabry's disease. A typical manifestation of reactions to various drugs is the fixed drug eruption of penile skin. The differential diagnosis of various forms of balanoposthitis may be difficult and requires histological investigations (e.g. plasma cell balanitis or Zoon's disease). In contrast, the clinical manifestation of lichen sclerosus et atrophicus is easy to recognize. The clinical relevance of this disease is due to phimosis and problems during sexual intercourse. PMID- 27250105 TI - [Cell biology and physiology of male reproduction]. AB - BACKGROUND: An adequate and undisturbed generation of fertile sperm is a prerequisite for fatherhood. Therefore, spermatogenesis is of central importance for male fertility. The testes, however, not only hold the germinal epithelium as the sperm-generating organ but also acts as a gland releasing androgens to control male reproductive function. This dual testicular function provides options to couple and coordinate spermatogenesis and steroidogenesis. METHODS: The regulation of both processes via the hypothalamus-pituitary-gonadal axis is arranged via feedback loops, which are interconnected but also enable separate modulation of germ cell production and endocrine activity. Many parameters of gonadal function can be determined and provide information about physiological or pathological changes of testis function. OBJECTIVES: This article introduces the physiological basics of testis function and presents the repertoire of endpoints determined in clinical andrology to facilitate a deeper understanding for clinical diagnostics of male fertility. PMID- 27250106 TI - Electrostatics analysis of the mutational and pH effects of the N-terminal domain self-association of the major ampullate spidroin. AB - Spider silk is a fascinating material combining mechanical properties such as maximum strength and high toughness comparable or better than man-made materials, with biocompatible degradability characteristics. Experimental measurements have shown that pH triggers the dimer formation of the N-terminal domain (NTD) of the major ampullate spidroin 1 (MaSp 1). A coarse-grained model accounting for electrostatics, van der Waals and pH-dependent charge-fluctuation interactions, by means of Monte Carlo simulations, gave us a more comprehensive view of the NTD dimerization process. A detailed analysis of the electrostatic properties and free energy derivatives for the NTD homoassociation was carried out at different pH values and salt concentrations for the protein wild type and for several mutants. We observed an enhancement of dipole-dipole interactions at pH 6 due to the ionization of key amino acids, a process identified as the main driving force for dimerization. Analytical estimates based on the DVLO theory framework corroborate our findings. Molecular dynamics simulations using the OPEP coarse grained force field for proteins show that the mutant E17Q is subject to larger structural fluctuations when compared to the wild type. Estimates of the association rate constants for this mutant were evaluated by the Debye Smoluchowski theory and are in agreement with the experimental data when thermally relaxed structures are used instead of the crystallographic data. Our results can contribute to the design of new mutants with specific association properties. PMID- 27250108 TI - Genes associated with common variable immunodeficiency: one diagnosis to rule them all? AB - Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by hypogammaglobulinaemia, impaired production of specific antibodies after immunisation and increased susceptibility to infections. CVID shows a considerable phenotypical and genetic heterogeneity. In contrast to many other primary immunodeficiencies, monogenic forms count for only 2-10% of patients with CVID. Genes that have been implicated in monogenic CVID include ICOS, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), TNFRSF7 (CD27), IL21, IL21R, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R1, VAV1, RAC2, BLK, IKZF1 (IKAROS) and IRF2BP2 With the increasing number of disease genes identified in CVID, it has become clear that CVID is an umbrella diagnosis and that many of these genetic defects cause distinct disease entities. Moreover, there is accumulating evidence that at least a subgroup of patients with CVID has a complex rather than a monogenic inheritance. This review aims to discuss current knowledge regarding the molecular genetic basis of CVID with an emphasis on the relationship with the clinical and immunological phenotype. PMID- 27250109 TI - Evaluation of Automatically Assigned Job-Specific Interview Modules. AB - OBJECTIVE: In community-based epidemiological studies, job- and industry-specific 'modules' are often used to systematically obtain details about the subject's work tasks. The module assignment is often made by the interviewer, who may have insufficient occupational hygiene knowledge to assign the correct module. We evaluated, in the context of a case-control study of lymphoid neoplasms in Asia ('AsiaLymph'), the performance of an algorithm that provided automatic, real-time module assignment during a computer-assisted personal interview. METHODS: AsiaLymph's occupational component began with a lifetime occupational history questionnaire with free-text responses and three solvent exposure screening questions. To assign each job to one of 23 study-specific modules, an algorithm automatically searched the free-text responses to the questions 'job title' and 'product made or services provided by employer' using a list of module-specific keywords, comprising over 5800 keywords in English, Traditional and Simplified Chinese. Hierarchical decision rules were used when the keyword match triggered multiple modules. If no keyword match was identified, a generic solvent module was assigned if the subject responded 'yes' to any of the three solvent screening questions. If these question responses were all 'no', a work location module was assigned, which redirected the subject to the farming, teaching, health professional, solvent, or industry solvent modules or ended the questions for that job, depending on the location response. We conducted a reliability assessment that compared the algorithm-assigned modules to consensus module assignments made by two industrial hygienists for a subset of 1251 (of 11409) jobs selected using a stratified random selection procedure using module-specific strata. Discordant assignments between the algorithm and consensus assignments (483 jobs) were qualitatively reviewed by the hygienists to evaluate the potential information lost from missed questions with using the algorithm assigned module (none, low, medium, high). RESULTS: The most frequently assigned modules were the work location (33%), solvent (20%), farming and food industry (19%), and dry cleaning and textile industry (6.4%) modules. In the reliability subset, the algorithm assignment had an exact match to the expert consensus assigned module for 722 (57.7%) of the 1251 jobs. Overall, adjusted for the proportion of jobs in each stratum, we estimated that 86% of the algorithm assigned modules would result in no information loss, 2% would have low information loss, and 12% would have medium to high information loss. Medium to high information loss occurred for <10% of the jobs assigned the generic solvent module and for 21, 32, and 31% of the jobs assigned the work location module with location responses of 'someplace else', 'factory', and 'don't know', respectively. Other work location responses had <=8% with medium to high information loss because of redirections to other modules. Medium to high information loss occurred more frequently when a job description matched with multiple keywords pointing to different modules (29-69%, depending on the triggered assignment rule). CONCLUSIONS: These evaluations demonstrated that automatically assigned modules can reliably reproduce an expert's module assignment without the direct involvement of an industrial hygienist or interviewer. The feasibility of adapting this framework to other studies will be language- and exposure-specific. PMID- 27250110 TI - Sensitization of multidrug-resistant malignant cells by liposomes co encapsulating doxorubicin and chloroquine through autophagic inhibition. AB - Adenosine triphosphate (ATP)-binding cassette (ABC) transporters play a key role in the development of multidrug resistance (MDR) in cancer cells. P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) are important proteins in this superfamily which are widely expressed on the membranes of multidrug resistance (MDR) cancer cells. Besides, upregulation of cellular autophagic responses is considered a contributing factor for MDR in cancer cells. We designed a liposome system co-encapsulating a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and a typical autophagy inhibitior (chloroquine phosphate, CQ) at a weight ratio of 1:2 and investigated its drug resistance reversal mechanism. MTT assay showed that the IC50 of DOX/CQ co-encapsulated liposome in DOX-resistant human breast cancer cells (MCF7/ADR) was 4.7 +/- 0.2 MUM, 5.7-fold less than that of free DOX (26.9 +/- 1.9 MUM), whereas it was 19.5 fold in doxorubicin-resistant human acute myelocytic leukemia cancer cells (HL60/ADR) (DOX/CQ co-encapsulated liposome 1.2 +/- 0.1 MUM, free DOX 23.4 +/- 2.8 MUM). The cellular uptake of DOX increased upon addition of free CQ, indicating that CQ may interact with P-gp and MRP1; however, the expressions of P gp and MRP1 remained unchanged. In contrast, the expression of the autophagy related protein LC3-II increased remarkably. Therefore, the mechanism of MDR reversal may be closely related to autophagic inhibition. Evaluation of anti tumor activity was achieved in an MCF-7/ADR multicellular tumor spheroid model and transgenic zebrafish model. DOX/CQ co-encapsulated liposome exerted a better anti-tumor effect in both models than that of liposomal DOX or DOX alone. These findings suggest that encapsulating CQ with DOX in liposomes significantly improves the sensitivity of DOX in DOX-resistant cancer cells. PMID- 27250111 TI - Transgressive women don't deserve protection: young men's narratives of sexual violence against women in rural Papua New Guinea. AB - Sexual violence against women and girls is commonplace in Papua New Guinea (PNG). While the experiences of women are rightly given central place in institutional responses to sexual violence, the men who perpetrate violence are often overlooked, an oversight that undermines the effectiveness of prevention efforts. This paper draws on interviews conducted with young men as part of a qualitative longitudinal study of masculinity and male sexuality in a rural highland area of PNG. It explores one aspect of male sexuality: men's narratives of sexual violence. Most striking from the data is that the collective enactment of sexual violence against women and girls is reported as an everyday and accepted practice amongst young men. However, not all women and girls were described as equally at risk, with those who transgress gender roles and roles inscribed and reinforced by patriarchal structures, at greater risk. To address this situation, efforts to reduce sexual violence against women and girls require an increased focus on male centred intervention to critically engage with the forms of patriarchal authority that give license to sexual violence. Understanding the perceptions and experiences of men as perpetrators of sexual violence is a critical first step in the process of changing normative perceptions of gender, a task crucial to reducing sexual violence in countries such as PNG. PMID- 27250112 TI - Possible role of mitochondrial injury in Caulis Aristolochia manshuriensis induced chronic aristolochic acid nephropathy. AB - CONTEXT: The proximal tubular epithelial cells (PTECs) are the primary target of aristolochic acids and especially vulnerable to mitochondrial injury from insults of toxic xenobiotics. OBJECTIVES: This study aimed to investigate the possible role of mitochondrial injury in Caulis Aristolochia manshuriensis (CAM)-induced aristolochic acid nephropathy (AAN). MATERIALS AND METHODS: Male Sprague-Dawley rats were gavaged with CAM extract every other week for 1, 4, 8 and 12 weeks, respectively. RESULTS: The rats in the model group showed chronic AAN as evidenced by worsening kidney function evaluated by blood urea nitrogen, creatinine and proteinuria levels, and severe tubulointerstitial injury marked by massive tubular atrophy and interstitial fibrosis in kidney tissues. Moreover, overt apoptosis and impaired regeneration of PTECs were observed in AAN rats. Furthermore, the study revealed that mitochondria in PTECs were fragmented into small, punctuate suborganelles in AAN rats. Two mitochondrial respiratory chain proteins, mitochondrial DNA (mtDNA)-encoded cytochrome c oxidase subunit I (COX I) and nuclear DNA-encoded nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)-1beta subcomplex 8 (NDUFbeta8), were both down-regulated after one week of CAM treatment. However, with AAN progression, NDUFbeta8 level restored, while COX-I level maintained low. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), master regulator of mitochondrial biogenesis, was significantly down-regulated at week 4 and week 8, but significantly up-regulated at week 12. In addition, mtDNA copy number reduced markedly along with AAN progression. DISCUSSION AND CONCLUSION: A rat model of chronic AAN was successfully reproduced by gavage with CAM extract. Dynamic changes of mitochondrial injury induced by CAM might contribute to the AAN progression. PMID- 27250113 TI - Detection of serous precursor lesions in resected fallopian tubes from patients with benign diseases and a relatively low risk for ovarian cancer. AB - The frequency of ovarian cancers in Japan has increased; however, doubts have been raised concerning the mechanism by which high-grade serous adenocarcinomas (HGSCs) arise. Conventionally, HGSC is thought to originate from the ovarian surface epithelium or epithelial inclusion cyst. However, recent data indicate that HGSCs may in fact develop from precursor lesions in the fallopian tube, including epithelia with a p53 signature, serous tubal intraepithelial carcinomas (STICs), secretory cell outgrowths (SCOUTs), and tubal intraepithelial lesions in transition (TILT). Here, we determined the frequency of these fallopian tube precursors in surgically excised samples from 123 patients with benign pelvic diseases. We identified 12 cases with a p53 signature (9.7%), 26 with observable SCOUTs (21.1%), and 4 with TILT (3.2%), but no STIC cases. Although the lifetime risk for developing ovarian cancer is only around 1.4% for women without germ line mutations, it is important to evaluate the presence of precursor lesions to understand HGSC pathogenesis better. Taken together, salpingectomy appears to be an option for women who are past their childbearing age and plan to undergo elective pelvic surgery. To our knowledge, this is the first study to investigate the presence of these specific precursors post-salpingectomy in low-risk patients. PMID- 27250114 TI - Severe Obesity Is Associated With Increased Risk of Early Complications and Extended Length of Stay Following Coronary Artery Bypass Grafting Surgery. AB - BACKGROUND: Better understanding of the relationship between obesity and postsurgical adverse outcomes is needed to provide quality and efficient care. We examined the relationship of obesity with the incidence of early adverse outcomes and in-hospital length of stay following coronary artery bypass grafting surgery. METHODS AND RESULTS: We analyzed data from 7560 patients who underwent coronary artery bypass grafting. Using body mass index (BMI; in kg/m(2)) of 18.5 to 24.9 as a reference, the associations of 4 BMI categories (25.0-29.9, 30.0-34.9, 35.0 39.9, and >=40.0) with rates of operative mortality, overall early complications, subgroups of early complications (ie, infection, renal and pulmonary complications), and length of stay were assessed while adjusting for clinical covariates. There was no difference in operative mortality; however, higher risks of overall complications were observed for patients with BMI 35.0 to 39.9 (adjusted odds ratio 1.35, 95% CI 1.11-1.63) and >=40.0 (adjusted odds ratio 1.56, 95% CI 1.21-2.01). Subgroup analyses identified obesity as an independent risk factor for infection (BMI 30.0-34.9: adjusted odds ratio 1.60, 95% CI 1.24 2.05; BMI 35.0-39.9: adjusted odds ratio 2.34, 95% CI 1.73-3.17; BMI >=40.0: adjusted odds ratio 3.29, 95% CI 2.30-4.71). Median length of stay was longer with BMI >=40.0 than with BMI 18.5 to 24.9 (median 7.0 days [interquartile range 5 to 10] versus 6.0 days [interquartile range 5 to 9], P=0.026). CONCLUSIONS: BMI >=40.0 was an independent risk factor for longer length of stay, and infection was a potentially modifiable risk factor. Greater perioperative attention and intervention to control the risks associated with infection and length of stay in patients with BMI >=40.0 may improve patient care quality and efficiency. PMID- 27250115 TI - Use of diagnostic coronary angiography in women and men presenting with acute myocardial infarction: a matched cohort study. AB - BACKGROUND: Based on evident sex-related differences in the invasive management of patients presenting with acute myocardial infarction (AMI), we sought to identify predictors of diagnostic coronary angiography (DCA) and to investigate reasons for opting out an invasive strategy in women and men. METHODS: The study was designed as a matched cohort study. We randomly selected 250 female cases from a source population of 4000 patients hospitalized with a first AMI in a geographically confined region of Denmark from January 2010 to November 2011. Each case was matched to a male control on age and availability of cardiac invasive facilities at the index hospital. We systematically reviewed medical records for risk factors, comorbid conditions, clinical presentation, and receipt of DCA. Clinical justifications, as stated by the treating physician, were noted for the subset of patients who did not receive a DCA. RESULTS: Overall, 187 women and 198 men received DCA within 60 days (75 % vs. 79 %, hazard ratio: 0.82 [0.67 1.00], p = 0.047).In the subset of patients who did not receive a DCA (n = 114), clinical justifications for opting out an invasive strategy was not documented for 21 patients (18.4 %). Type 2 myocardial infarction was noted in 11 patients (women versus men; 14.5 % vs. 3.8 %, p = 0.06) and identified as a potential confounder of the sex-DCA relationship. Receipt of DCA was predicted by traditional risk factors for ischaemic heart disease (family history of cardiovascular disease, hypercholesterolemia, and smoking) and clinical presentation (chest pain, ST-segment elevations). Although prevalent in both women and men, the presence of relative contraindications did not prohibit the use of DCA. CONCLUSION: In this matched cohort of patients with a first AMI, women and men had different clinical presentations despite similar age. However, no differences in the distribution of relative contraindications for DCA were found between the sexes. Type 2 MI posed a potentiel confounder for the sex related differences in the use of DCA. Importantly,clinical justification for opting out an invasive strategy was not documented in almost one fifth of patients not receiving a DCA. PMID- 27250116 TI - HER2 status and disparities in luminal breast cancers. AB - National Comprehensive Care Network guidelines for adjuvant treatment of invasive breast cancer are based on HER2 and hormone receptor (HR) status, where HR+ disease encompasses all estrogen receptor (ER)+ and/or progesterone receptor (PR)+ tumors. We sought to explore clinical and demographic differences among patients with HR+ breast cancer subtypes, and the role of HER2 status, age, race/ethnicity, and socioeconomic status (SES) in disease risk. We evaluated breast cancer subtype distribution, defined by HR and HER2 status, using patient clinical, demographic, and socioeconomic characteristics. Differences in HR categories by demographic and tumor characteristics were examined using chi squared tests. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) to quantify associations between breast cancer HR status and demographic factors. We found that differences in HR+ (ER /PR+ vs. ER+/PR- or ER+/PR+) tumor biology are likely clinically significant and may play a role in breast cancer, regardless of HER2 status. While clinical and patient characteristics differed within each luminal subtype, we found disparities in SES only among Luminal A (HR+/HER2-) tumors. Among HR+/HER2- cases, we observed that ER-/PR+ patients tend to live in areas of higher poverty (OR = 1.20, 95% CI = 1.03-1.40) and are 70% more likely to be aged 50 years or older. However, this pattern was not found in women with Luminal B (HR+/HER2+) disease (Poverty OR = 0.98, 95% CI = 0.76-1.27; Age OR = 1.01, 95% CI = 0.81 1.26). Racial/ethnic disparities among non-Hispanic black and Hispanic women persisted across HR+/HER2- cases compared to non-Hispanic white women. Our findings suggest that while race/ethnicity and SES are correlated, each plays an independent role in contributing to disease among Luminal A tumors. Further study is needed to investigate how tumor biology, race/ethnicity, and socioeconomic disparities among HR+/HER2- cases may contribute to poorer patient prognosis. PMID- 27250117 TI - Development of a survey instrument to measure patient experience of integrated care. AB - BACKGROUND: Healthcare systems are working to move towards more integrated, patient-centered care. This study describes the development and testing of a multidimensional self-report measure of patients' experiences of integrated care. METHODS: Random-digit-dial telephone survey in 2012 of 317 adults aged 40 years or older in the San Francisco region who had used healthcare at least twice in the past 12 months. One-time cross-sectional survey; psychometric evaluation to confirm dimensions and create multi-item scales. Survey data were analyzed using VARCLUS and confirmatory factor analysis and internal consistency reliability testing. RESULTS: Scales measuring five domains were confirmed: coordination within and between care teams, navigation (arranging appointments and visits), communication between specialist and primary care doctor, and communication between primary care doctor and specialist. Four of these demonstrated excellent internal consistency reliability. Mean scale scores indicated low levels of integration. CONCLUSION: These scales measuring integrated care capture meaningful domains of patients' experiences of health care. The low levels of care integration reported by patients in the study sample suggest that these types of measures should be considered in ongoing evaluations of health system performance and improvement. Further research should examine whether differences in patient experience of integrated care are associated with differences in the processes and outcomes of care received. PMID- 27250118 TI - Progression of experimental chronic Aleutian mink disease virus infection. AB - BACKGROUND: Aleutian mink disease virus (AMDV) is found world-wide and has a major impact on mink health and welfare by decreasing reproduction and fur quality. In the majority of mink, the infection is subclinical and the diagnosis must be confirmed by serology or polymerase chain reaction (PCR). Increased knowledge based on a systematically description of clinical signs, pathology and histopathology might be a tool to reduce the risk of infection from subclinically infected mink to AMDV free herds. The aim of this study was to give a histopathological description of the progression of a chronic experimental infection with a currently circulating Danish strain of AMDV, Saeby/DEN/799.1/05. These results were compared with the pathogenesis of previously published AMDV stains. RESULTS: This experimental AMDV infection resulted in only decreased appetite and soft or discolored feces, primarily within the first 8 weeks after AMDV inoculation. Gross pathology revealed few and inconsistent findings mainly associated with the liver, spleen and kidneys. The majority of the AMDV inoculated wild type mink (n = 41) developed various histopathological changes consistent with AMDV infection in one or more organs: infiltrations of mononuclear cells in liver, kidney and brain, reduced density of lymphocytes and increased numbers of plasma cells in lymph nodes and spleen. Natural infection, as occurred in the sentinel sapphire mink (four of six mink), progressed similar to the experimentally inoculated mink. CONCLUSIONS: Experimental AMDV inoculation mainly resulted in subclinical infection with unspecific clinical signs and gross pathology, and more consistent histopathology appearing at any time after AMDV inoculation during the 24 weeks of observation. Thus, the observed histopathology substantiates AMDV infection and no correlation to time of inoculation was found. This confirms that diagnosing AMDV infection requires serology and/or PCR and the Saeby/DEN/799.1/05 AMDV strain results in histopathology consistent with other AMDV strains. PMID- 27250119 TI - Solitary splenic tuberculosis: a case report and review of the literature. AB - BACKGROUND: Tuberculosis remains one of the most prevalent and fatal infectious diseases in spite of considerable improvements in medical science. Tuberculosis is an important health problem in developing countries. There are few cases of solitary splenic tuberculosis reported in the literature internationally. Solitary splenic tuberculosis is extremely rare and is mostly seen in individuals with immunosuppression. Patients susceptible to acquiring splenic tuberculosis usually have some risk factors such as immunosuppression, pyogenic infections, splenic abnormalities, spleen trauma, sickle cell disease, and so on (Basa JV, Singh L, Jaoude WA, Sugiyama G, Int J Surg 8C:117-119,2015). CASE PRESENTATION: Here we report a case of surgically confirmed mass-forming solitary splenic tuberculosis in a 64-year-old woman who presented with abdominal discomfort for two months, but with no other symptoms. Laboratory data provided no specific information for diagnosis. Abdominal ultrasonography revealed a large hypoechoic lesion within the spleen. Computed tomography scan of the abdomen showed a solitary hypodense lesion. A diagnosis of solitary splenic tuberculosis was confirmed after a splenectomy was performed and histopathological examination revealed splenic tuberculosis. CONCLUSIONS: Solitary splenic tuberculosis is rare and associated with an immunocompetent patient is extremely rare. It is hard to correctly diagnose it by US or CT scan. PMID- 27250122 TI - Evaluation of the successive approximations method for acoustic streaming numerical simulations. AB - This work evaluates the successive approximations method commonly used to predict acoustic streaming by comparing it with a direct method. The successive approximations method solves both the acoustic wave propagation and acoustic streaming by solving the first and second order Navier-Stokes equations, ignoring the first order convective effects. This method was applied to acoustic streaming in a 2D domain and the results were compared with results from the direct simulation of the Navier-Stokes equations. The velocity results showed qualitative agreement between both methods, which indicates that the successive approximations method can describe the formation of flows with recirculation. However, a large quantitative deviation was observed between the two methods. Further analysis showed that the successive approximation method solution is sensitive to the initial flow field. The direct method showed that the instantaneous flow field changes significantly due to reflections and wave interference. It was also found that convective effects contribute significantly to the wave propagation pattern. These effects must be taken into account when solving the acoustic streaming problems, since it affects the global flow. By adequately calculating the initial condition for first order step, the acoustic streaming prediction by the successive approximations method can be improved significantly. PMID- 27250121 TI - Pulmonary neuroendocrine carcinoma mimicking neurocysticercosis: a case report. AB - BACKGROUND: Neurocysticercosis occurs when the eggs of the pork tapeworm (Taenia solium) migrate and hatch into larvae within the central nervous system. Neurocysticercosis is the most common cause of seizures in the developing world and is characterized on brain imaging by cysts in different stages of evolution. In Canada, cases of neurocysticercosis are rare and most of these patients acquire the disease outside of Canada. We report the case of a patient with multiple intracranial lesions whose history and diagnostic imaging were consistent with neurocysticercosis. Pathological investigations ultimately demonstrated that her brain lesions were secondary to malignancy. Brain metastases are considered to be the most common cause of intracranial cystic lesions. CASE PRESENTATION: We present the case of a 60-year-old Canadian-born Caucasian woman with a subacute history of ataxia, lower extremity hyper reflexia, and otalgia who resided near a pig farm for most of her childhood. Computed tomography and magnetic resonance imaging showed that she had multiple heterogeneous intracranial cysts, suggestive of neurocysticercosis. Despite a heavy burden of disease, serological tests for cysticercosis were negative. This result and a lack of the central scolices on neuroimaging that are pathognomonic of neurocysticercosis prompted whole-body computed tomography imaging to identify another etiology. The whole-body computed tomography revealed right hilar lymphadenopathy associated with soft tissue nodules in her chest wall and abdomen. A biopsy of an anterior chest wall nodule demonstrated high-grade poorly differentiated carcinoma with necrosis, which stained strongly positive for thyroid transcription factor-1 and synaptophysin on immunohistochemistry. A diagnosis of stage 4 metastatic small cell neuroendocrine carcinoma was made and our patient was referred for oncological palliative treatment. CONCLUSIONS: This case illustrates the importance of the diagnostic approach to intracranial lesions. Our patient's diagnosis of neuroendocrine carcinoma was delayed because of her nontraditional presentation. Despite extensive metastatic burden, the lack of perilesional edema and the identification of lesions appearing to be in various stages of development led to a pursuit of neurocysticercosis as the diagnosis. The absence of constitutional symptoms should not discount the possibility of malignancy from the differential diagnosis. PMID- 27250120 TI - The N3RO trial: a randomised controlled trial of docosahexaenoic acid to reduce bronchopulmonary dysplasia in preterm infants < 29 weeks' gestation. AB - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major cause of mortality and long-term respiratory and neurological morbidity in very preterm infants. While survival rates of very preterm infants have increased over the past two decades there has been no decrease in the rate of BPD in surviving infants. Evidence from animal and human studies has suggested potential benefits of docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, in the prevention of chronic lung disease. This randomised controlled trial aims to determine the effectiveness of supplementary DHA in reducing the rate of BPD in infants less than 29 weeks' gestation. METHODS/DESIGN: This is a multicentre, parallel group, randomised, blinded and controlled trial. Infants born less than 29 weeks' gestation, within 3 days of first enteral feed and with parent informed consent are eligible to participate. Infants will be randomised to receive an enteral emulsion containing DHA or a control emulsion without DHA. The DHA emulsion will provide 60 mg/kg/day of DHA. The study emulsions will continue to 36 weeks' postmenstrual age (PMA). The primary outcome is BPD as assessed by the requirement for supplemental oxygen and/or assisted ventilation at 36 weeks' PMA. Secondary outcomes include the composite of death or BPD; duration of respiratory support and hospitalisation, major neonatal morbidities. The target sample size is 1244 infants (622 per group), which will provide 90 % power to detect a clinically meaningful absolute reduction of 10 % in the incidence of BPD between the DHA and control emulsion (two tailed alpha =0.05). DISCUSSION: DHA supplementation has the potential to reduce respiratory morbidity in very preterm infants. This multicentre trial will provide evidence on whether an enteral DHA supplement reduces BPD in very preterm infants. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12612000503820 . Registered 09 May 2012. PMID- 27250123 TI - Auditory localization by subjects with unilateral tinnitus. AB - Tinnitus is associated with changes in neural activity. How such alterations impact the localization ability of subjects with tinnitus remains largely unexplored. In this study, subjects with self-reported unilateral tinnitus were compared to subjects with matching hearing loss at high frequencies and to normal hearing subjects in horizontal and vertical plane localization tasks. Subjects were asked to localize a pink noise source either alone or over background noise. Results showed some degree of difference between subjects with tinnitus and subjects with normal hearing in horizontal plane localization, which was exacerbated by background noise. However, this difference could be explained by different hearing sensitivities between groups. In vertical plane localization there was no difference between groups in the binaural listening condition, but in monaural listening the tinnitus group localized significantly worse with the tinnitus ear. This effect remained when accounting for differences in hearing sensitivity. It is concluded that tinnitus may degrade auditory localization ability, but this effect is for the most part due to the associated levels of hearing loss. More detailed studies are needed to fully disentangle the effects of hearing loss and tinnitus. PMID- 27250124 TI - Sparse feature learning for instrument identification: Effects of sampling and pooling methods. AB - Feature learning for music applications has recently received considerable attention from many researchers. This paper reports on the sparse feature learning algorithm for musical instrument identification, and in particular, focuses on the effects of the frame sampling techniques for dictionary learning and the pooling methods for feature aggregation. To this end, two frame sampling techniques are examined that are fixed and proportional random sampling. Furthermore, the effect of using onset frame was analyzed for both of proposed sampling methods. Regarding summarization of the feature activation, a standard deviation pooling method is used and compared with the commonly used max- and average-pooling techniques. Using more than 47 000 recordings of 24 instruments from various performers, playing styles, and dynamics, a number of tuning parameters are experimented including the analysis frame size, the dictionary size, and the type of frequency scaling as well as the different sampling and pooling methods. The results show that the combination of proportional sampling and standard deviation pooling achieve the best overall performance of 95.62% while the optimal parameter set varies among the instrument classes. PMID- 27250126 TI - Influence of laminate sequence and fabric type on the inherent acoustic nonlinearity in carbon fiber reinforced composites. AB - This paper presents the study of influence of laminate sequence and fabric type on the baseline acoustic nonlinearity of fiber-reinforced composites. Nonlinear elastic wave techniques are increasingly becoming popular in detecting damage in composite materials. It was earlier observed by the authors that the non classical nonlinear response of fiber-reinforced composite is influenced by the fiber orientation [Chakrapani, Barnard, and Dayal, J. Acoust. Soc. Am. 137(2), 617-624 (2015)]. The current study expands this effort to investigate the effect of laminate sequence and fabric type on the non-classical nonlinear response. Two hypotheses were developed using the previous results, and the theory of interlaminar stresses to investigate the influence of laminate sequence and fabric type. Each hypothesis was tested by capturing the nonlinear response by performing nonlinear resonance spectroscopy and measuring frequency shifts, loss factors, and higher harmonics. It was observed that the laminate sequence can either increase or decrease the nonlinear response based on the stacking sequence. Similarly, tests were performed to compare unidirectional fabric and woven fabric and it was observed that woven fabric exhibited a lower nonlinear response compared to the unidirectional fabric. Conjectures based on the matrix properties and interlaminar stresses were used in an attempt to explain the observed nonlinear responses for different configurations. PMID- 27250125 TI - Multi-tone suppression of distortion-product otoacoustic emissions in humans. AB - The purpose of this study was to investigate the combined effect of multiple suppressors. Distortion-product otoacoustic emission (DPOAE) measurements were made in normal-hearing participants. Primary tones had fixed frequencies (f2 = 4000 Hz; f1 / f2 = 1.22) and a range of levels. Suppressor tones were at three frequencies (fs = 2828, 4100, 4300 Hz) and range of levels. Decrement was defined as the attenuation in DPOAE level due to the presence of a suppressor. A measure of suppression called suppressive intensity was calculated by an equation previously shown to fit DPOAE suppression data. Suppressor pairs, which were the combination of two different frequencies, were presented at levels selected to have equal single-suppressor decrements. A hybrid model that represents a continuum between additive intensity and additive attenuation best described the results. The suppressor pair with the smallest frequency ratio produced decrements that were more consistent with additive intensity. The suppressor pair with the largest frequency ratio produced decrements at the highest level that were consistent with additive attenuation. Other suppressor-pair conditions produced decrements that were intermediate between these two alternative models. The hybrid model provides a useful framework for representing the observed range of interaction when two suppressors are combined. PMID- 27250127 TI - Effects of complex tonal stimuli on latency and amplitude of a late auditory evoked potential. AB - An optimum stimulus for evoking late auditory potentials is not well established. A typical stimulus for clinical purposes is either a brief speech signal or a brief single-frequency tone. Based on previous research, it is reasonable to assume that a complex stimulus may enhance waveform morphology relative to a single-frequency stimulus. The current project investigated the effects on P1 latency and P1/N1 amplitude of a two-frequency complex stimulus with the second frequency having either a dissonant or harmonic relationship to a single frequency reference stimulus. An 80 ms 1000 Hz tone with 10 ms rise/fall times served as the reference stimulus. The two-frequency complex stimuli consisted of the reference (1000 Hz) frequency mixed with a second frequency of equal duration and amplitude at 1100, 1250, 1500, 2000, or 4000 Hz, resulting in three dissonant and two harmonic stimuli. One dissonant stimulus (1000 + 1100 Hz) was designed to fall within the critical band of the reference stimulus. Stimuli were presented in a counterbalanced order to 20 normal hearing adult subjects. Two replicate runs were obtained for each stimulus condition. Results showed that the complex stimuli had no significant effect on P1 latency relative to the reference stimulus, but produced a significant increase in P1/N1 amplitude for the harmonic stimuli. PMID- 27250128 TI - Sound transmission loss of double plates with an air cavity between them in a rigid duct. AB - In this paper, the sound transmission loss (STL) of thin double plates with an air cavity between them in a rigid duct is considered using an analytical approach. The vibration motion of the plate and sound pressure field are expanded in terms of an infinite series of the modal functions. Under the plane wave condition, a low frequency solution is derived by including the first few symmetric modes. It is determined that the peak frequencies of the double plates coincide with those of each single plate. When the two plates are identical, the STL becomes zero at the natural frequencies of the single plate. However, when the two plates are not identical, the STL is always greater than zero. The location and amplitude of the dips are investigated using an approximate solution when the cavity depth is very small. It is observed that dividing the single plate into two plates with an air cavity in between degrades the STL in the low frequency range, while the equivalent surface mass density is preserved. However, when the cavity depth is not small, the STL of the single plate can be smaller than that of the double plates. PMID- 27250129 TI - Mid-bandwidth loudness depression in hearing-impaired listeners. AB - The loudness of a bandpass-filtered noise depends on its bandwidth. For bandwidths larger than a critical bandwidth, loudness increases as the bandwidth increases, an effect commonly referred to as spectral loudness summation. For bandwidths smaller than the critical bandwidth, it was shown recently for normal hearing listeners that loudness decreases as the bandwidth increases. This study investigated if listeners with a hearing impairment of primarily cochlear origin also showed this effect. Levels at equal loudness between a 1500-Hz pure-tone reference and noise-band targets centered at 1500 Hz were measured for bandwidths in the range from 15 to 1620 Hz. The reference level was adjusted individually on the basis of the audiogram. The average level difference at equal loudness increased from 0 dB at 15 Hz up to a maximum of about 4 dB at 810 Hz. Thus, the mid-bandwidth loudness depression is also observed for hearing-impaired listeners. PMID- 27250132 TI - Suppression of bending waves in a beam using resonators with different separation lengths. AB - This work is concerned with the suppression of a bending wave in a beam using resonators. Particular focus is put on the separation length between resonators. It is demonstrated that, for a beam with identical resonators attached at equal intervals, the bending wave transmission efficiency varies with respect to the separation length. The phenomena and the underlying physics are investigated by resorting to a simple beam model having two resonators resting on it. The two resonators are coupled over the segment through various bending wave components, comprising both propagating waves and evanescent waves, generated at the resonator locations where the beam encounters impedance discontinuities. The separation length, specifying the phase change of the propagating waves and the amplitude decay of the evanescent waves travelling from one resonator to the other, is thereby the parameter determining the extent to which the resonators would be coupled and the degree of the power that is transmitted. Results show, qualitatively, the difference in the working mechanism of the resonators in different separation length regions, with criteria being defined to distinguish those regions. Particularly, in the intermediate separation region, the evanescent waves are shown to play an important role in the coupling and are responsible for transmitting power, comparable with that transmitted by propagating waves, to the far field. PMID- 27250130 TI - Ultrasound and acoustic analysis of sibilant fricatives in preadolescents and adults. AB - This study describes the production of sibilant fricatives /s/ and /?/, comparing Scottish English speaking preadolescent children with adults. The materials were the sequences /eCa/ and /eCi/ produced by 15 adults and 15 children aged between 10 and 12 years old. Quantitative analyses were carried out on both spectral information and on ultrasound imaging data on tongue shape, taken from nine successive time points during the fricative. The two groups of speakers were very similar to each other in the articulatory and acoustic characteristics distinguishing the two fricatives. Age-related differences in the fricative centroid measure occurred at consonant-vowel boundaries, with lower values in the preadolescents. Within-speaker variability was mostly similar across age groups, with the exception of the fricative centroid for /?/, which was significantly more variable in preadolescents than in adults. Throughout the consonant duration, both groups consistently differentiated between the two consonants in both the fricative centroid and in one measure of tongue shape. PMID- 27250134 TI - Flight parameter estimation using instantaneous frequency and time delay measurements from a three-element planar acoustic array. AB - The acoustic signal emitted by a turbo-prop aircraft consists of a strong narrowband tone superimposed on a broadband random component. A ground-based three-element planar acoustic array can be used to estimate the full set of flight parameters of a turbo-prop aircraft in transit by measuring the time delay (TD) between the signal received at the reference sensor and the signal received at each of the other two sensors of the array over a sufficiently long period of time. This paper studies the possibility of using instantaneous frequency (IF) measurements from the reference sensor to improve the precision of the flight parameter estimates. A simplified Cramer-Rao lower bound analysis shows that the standard deviations in the estimates of the aircraft velocity and altitude can be greatly reduced when IF measurements are used together with TD measurements. Two flight parameter estimation algorithms that utilize both IF and TD measurements are formulated and their performances are evaluated using both simulated and real data. PMID- 27250133 TI - Dynamic vocal fold parameters with changing adduction in ex-vivo hemilarynx experiments. AB - Ex-vivo hemilarynx experiments allow the visualization and quantification of three-dimensional dynamics of the medial vocal fold surface. For three excised human male larynges, the vibrational output, the glottal flow resistance, and the sound pressure during sustained phonation were analyzed as a function of vocal fold adduction for varying subglottal pressure. Empirical eigenfunctions, displacements, and velocities were investigated along the vocal fold surface. For two larynges, an increase of adduction level resulted in an increase of the glottal flow resistance at equal subglottal pressures. This caused an increase of lateral and vertical oscillation amplitudes and velocity indicating an improved energy transfer from the airflow to the vocal folds. In contrast, the third larynx exhibited an amplitude decrease for rising adduction accompanying reduction of the flow resistance. By evaluating the empirical eigenfunctions, this reduced flow resistance was assigned to an unbalanced oscillation pattern with predominantly lateral amplitudes. The results suggest that adduction facilitates the phonatory process by increasing the glottal flow resistance and enhancing the vibrational amplitudes. However, this interrelation only holds for a maintained balanced ratio between vertical and lateral displacements. Indeed, a balanced vertical-lateral oscillation pattern may be more beneficial to phonation than strong periodicity with predominantly lateral vibrations. PMID- 27250135 TI - Comment on "Reconstructing surface wave profiles from reflected acoustic pulses" [J. Acoust. Soc. Am. 133(5), 2597-2611 (2013)]. AB - A computationally efficient, time-domain Helmholtz-Kirchhoff (H-K) integral was derived and applied to reconstructing surface wave profiles from reflected acoustic pulses [Walstead and Deane, J. Acoust. Soc. Am. 133, 2597-2611 (2013)]. However, the final form of the integral equation incorporating a stationary phase approximation contained a complex phase term exp(ipi/4), which cannot be treated as a simple time delay. In this work, a real time-domain H-K integral is presented that includes an additional Hilbert transform of the time-derivative of the transmitted pulse. Numerical simulation with a sinusoidal surface shows good agreement between the real time-domain formulation and exact H-K integral, while achieving a significant improvement in computational speed (e.g., 2 orders of magnitude). PMID- 27250136 TI - Masked threshold for noise bands masked by narrower bands of noise: Effects of masker bandwidth and center frequency. AB - This paper examines how masked thresholds depend on the masker bandwidth and center frequency when the masker has a smaller bandwidth than the signal. The signal bandwidth was equal to the equivalent rectangular bandwidth of the auditory filter and the masker bandwidth was 0.1, 0.35, or 0.6 times the signal bandwidth. The masker and signal were centered at the same frequency of 257, 697, 1538, 3142, or 6930 Hz. Masked thresholds were estimated using a two-interval two alternative forced-choice paradigm and a three-down one-up adaptive staircase method. Masked thresholds increased with increasing masker bandwidth and were lowest for medium center frequencies. PMID- 27250137 TI - Understanding acoustic methods for cement bond logging. AB - Well cementation is important for oil/gas production, underground gas storage, and CO2 storage, since it isolates the reservoir layers from aquifers to increase well integrity and reduce environmental footprint. This paper analyzes wave modes of different sonic/ultrasonic methods for cement bonding evaluation. A Two dimensional finite difference method is then used to simulate the wavefield for the ultrasonic methods in the cased-hole models. Waveforms of pulse-echo method from different interfaces in a good bonded well are analyzed. Wavefield of the pitch-catch method for free casing, partial or full bonded models with ultra-low density cement are studied. Based on the studies, the modes in different methods are considered as follows: the zero-order symmetric Leaky-Lamb mode (S0) for sonic method, the first-order symmetric Leaky-Lamb mode (S1) for the pulse-echo method, and the zero-order anti-symmetric Leaky-Lamb mode (A0) for the pitch catch method. For the sonic method, a directional transmitter in both the azimuth and axial directions can generate energy with a large incidence angle and azimuth resolution, which can effectively generate S0 and break out the azimuth limitation of the conventional sonic method. Although combination of pulse-echo and pitch-catch methods can determine the bonding condition of the third interface for the ultra-low density cement case, the pitch-catch cannot tell the fluid annulus thickness behind casing for the partial bonded cased-hole. PMID- 27250138 TI - Ocean ambient sound south of Bermuda and Panama Canal traffic. AB - Comparisons of current and historic ocean ambient noise levels are rare, especially in the North Atlantic. Recent (2013-2014) monthly patterns in ocean ambient sound south of Bermuda were compared to those recorded at the same location in 1966. Additionally, trends in ocean traffic, in particular, Panama Canal traffic, over this time were also investigated. One year of ocean ambient noise measurements were collected in 1966 using cabled, omnidirectional hydrophones at the U.S. Navy Tudor Hill Laboratory in Bermuda, and repeat measurements were collected at the same location from June 2013-May 2014 using a High-frequency Acoustic Recording Package. Average monthly pressure spectrum levels at 44 Hz increased 2.8 +/- 0.8 dB from 1966 to 2013, indicating an average increase of 0.6 dB/decade. This low level of increase may be due to topographic shielding at this site, limiting it to only southern exposure, and the limit in the number of ship transits through the Panama Canal, which did not change substantially during this time. The impending expansion of the Canal, which will enable the transit of larger ships at twice the current rate, is likely to lead to a substantial increase in ocean ambient sound at this location in the near future. PMID- 27250139 TI - Acoustic reflections in the water column of Krishna-Godavari offshore basin, Bay of Bengal. AB - Seismic oceanographic studies from various oceans worldwide have indicated that the acoustic reflections are mostly observed along thermal boundaries within the water column. However, the authors present a case study of seismic data from Krishna-Godavari Basin which shows that salinity variations also play an important role in the occurrence of water column reflections. The observed reflection is modeled using the reflectivity series derived from the salinity and temperature profiles from a nearby Conductivity-Temperature-Depth (CTD) location. Sensitivity analysis of temperature and salinity on soundspeed shows that the effect of salinity cannot be ignored for modeling acoustic reflections. The synthetic seismogram matches well with the observed reflection seismic data. Remarkable similarities between the reflection seismic and the salinity profile in the upper thermocline suggest the importance of salinity variations on the water column reflection. Furthermore, impedance inversion of the reflectivity data reveals several thermohaline structures in the water column. The origin of these thermohaline structures is largely unaddressed and may be attributed to the fresh water influx coming from Himalayan and Peninsular rivers or due to the presence of different water masses in the Indian Ocean which warrants a detailed study using concurrent seismic and CTD data. PMID- 27250140 TI - Effects of musical and linguistic experience on categorization of lexical and melodic tones. AB - This study investigated the categorization of Mandarin lexical tones and music melodic tones by listeners differing in linguistic and musical experience (English musicians, English non-musicians, and Mandarin non-musicians). Linguistic tonal continua were created from the Mandarin rising to level, and falling to level tones. Melodic continua were created by varying the note D under the context of C and E. The tasks involved tone discrimination and identification. Results revealed that musical training facilitated Mandarin tone categorization, with English musicians' tone identification approximating native Mandarin patterns, being more categorical than English non-musicians'. However, English musicians showed higher discrimination accuracy than Mandarin listeners but not English non-musicians. This suggests that musical experience was not advantageous in discriminating linguistic tonal variations, which requires listeners to ignore subtle physical differences in order to make categorical judgments. Similarly, Mandarin tone experience affected melodic tone identification, with Mandarin non-musicians approximating English musicians, showing more categorical patterns than English non-musicians. In contrast, Mandarin non-musicians' melodic discrimination was the poorest among the three groups, indicating that their experience with linguistic tone categorization may have decreased their sensitivity to fine-grained pitch variations. These results demonstrate bi-directional transfer of pitch proficiency between speech and music as a function of experience. PMID- 27250141 TI - Simulating electrical modulation detection thresholds using a biophysical model of the auditory nerve. AB - Modulation detection thresholds (MDTs) assess listeners' sensitivity to changes in the temporal envelope of a signal and have been shown to strongly correlate with speech perception in cochlear implant users. MDTs are simulated with a stochastic model of a population of auditory nerve fibers that has been verified to accurately simulate a number of physiologically important temporal response properties. The procedure to estimate detection thresholds has previously been applied to stimulus discrimination tasks. The population model simulates the MDT stimulus intensity relationship measured in cochlear implant users. The model also recreates the shape of the modulation transfer function and the relationship between MDTs and carrier rate. Discrimination based on fluctuations in synchronous firing activity predicts better performance at low carrier rates, but quantitative measures of modulation coding predict better neural representation of high carrier rate stimuli. Manipulating the number of fibers and a temporal integration parameter, the width of a sliding temporal integration window, varies properties of the MDTs, such as cutoff frequency and peak threshold. These results demonstrate the importance of using a multi-diameter fiber population in modeling the MDTs and demonstrate a wider applicability of this model to simulating behavioral performance in cochlear implant listeners. PMID- 27250142 TI - Asymptotic limits of some models for sound propagation in porous media and the assignment of the pore characteristic lengths. AB - Modeling of sound propagation in porous media requires the knowledge of several intrinsic material parameters, some of which are difficult or impossible to measure directly, particularly in the case of a porous medium which is composed of pores with a wide range of scales and random interconnections. Four particular parameters which are rarely measured non-acoustically, but used extensively in a number of acoustical models, are the viscous and thermal characteristic lengths, thermal permeability, and Pride parameter. The main purpose of this work is to show how these parameters relate to the pore size distribution which is a routine characteristic measured non-acoustically. This is achieved through the analysis of the asymptotic behavior of four analytical models which have been developed previously to predict the dynamic density and/or compressibility of the equivalent fluid in a porous medium. In this work the models proposed by Johnson, Koplik, and Dashn [J. Fluid Mech. 176, 379-402 (1987)], Champoux and Allard [J. Appl. Phys. 70(4), 1975-1979 (1991)], Pride, Morgan, and Gangi [Phys. Rev. B 47, 4964-4978 (1993)], and Horoshenkov, Attenborough, and Chandler-Wilde [J. Acoust. Soc. Am. 104, 1198-1209 (1998)] are compared. The findings are then used to compare the behavior of the complex dynamic density and compressibility of the fluid in a material pore with uniform and variable cross-sections. PMID- 27250143 TI - Temperature dependence of acoustic harmonics generated by nonlinear ultrasound wave propagation in water at various frequencies. AB - Ultrasound-based thermometry requires a temperature-sensitive acoustic parameter that can be used to estimate the temperature by tracking changes in that parameter during heating. The objective of this study is to investigate the temperature dependence of acoustic harmonics generated by nonlinear ultrasound wave propagation in water at various pulse transmit frequencies from 1 to 20 MHz. Simulations were conducted using an expanded form of the Khokhlov-Zabolotskaya Kuznetsov nonlinear acoustic wave propagation model in which temperature dependence of the medium parameters was included. Measurements were performed using single-element transducers at two different transmit frequencies of 3.3 and 13 MHz which are within the range of frequencies simulated. The acoustic pressure signals were measured by a calibrated needle hydrophone along the axes of the transducers. The water temperature was uniformly increased from 26 degrees C to 46 degrees C in increments of 5 degrees C. The results show that the temperature dependence of the harmonic generation is different at various frequencies which is due to the interplay between the mechanisms of absorption, nonlinearity, and focusing gain. At the transmit frequencies of 1 and 3.3 MHz, the harmonic amplitudes decrease with increasing the temperature, while the opposite temperature dependence is observed at 13 and 20 MHz. PMID- 27250144 TI - Durations required to distinguish noise and tone: Effects of noise bandwidth and frequency. AB - Perceptual audio coders exploit the masking properties of the human auditory system to reduce the bit rate in audio recording and transmission systems; it is intended that the quantization noise is just masked by the audio signal. The effectiveness of the audio signal as a masker depends on whether it is tone-like or noise-like. The determination of this, both physically and perceptually, depends on the duration of the stimuli. To gather information that might improve the efficiency of perceptual coders, the duration required to distinguish between a narrowband noise and a tone was measured as a function of center frequency and noise bandwidth. In experiment 1, duration thresholds were measured for isolated noise and tone bursts. In experiment 2, duration thresholds were measured for tone and noise segments embedded within longer tone pulses. In both experiments, center frequencies were 345, 754, 1456, and 2658 Hz and bandwidths were 0.25, 0.5, and 1 times the equivalent rectangular bandwidth of the auditory filter at each center frequency. The duration thresholds decreased with increasing bandwidth and with increasing center frequency up to 1456 Hz. It is argued that the duration thresholds depended mainly on the detection of amplitude fluctuations in the noise bursts. PMID- 27250145 TI - Influence of voxelization on finite difference time domain simulations of head related transfer functions. AB - The scattering around the human pinna that is captured by the Head-Related Transfer Functions (HRTFs) is a complex problem that creates uncertainties in both acoustical measurements and simulations. Within the simulation framework of Finite Difference Time Domain (FDTD) with axis-aligned staircase boundaries resulting from a voxelization process, the voxelization-based uncertainty propagating in the HRTF-captured sound field is quantified for one solid and two surface voxelization algorithms. Simulated results utilizing a laser-scanned mesh of Knowles Electronics Manikin for Acoustic Research (KEMAR) show that in the context of complex geometries with local topology comparable to grid spacing such as the human pinna, the voxelization-related uncertainties in simulations emerge at lower frequencies than the generally used accuracy bandwidths. Numerical simulations show that the voxelization process induces both random error and algorithm-dependent bias in the simulated HRTF spectral features. Frequencies fr below which the random error is bounded by various dB thresholds are estimated and predicted. Particular shortcomings of the used voxelization algorithms are identified and the influence of the surface impedance on the induced errors is studied. Simulations are also validated against measurements. PMID- 27250146 TI - Quantitative analysis of a frequency-domain nonlinearity indicator. AB - In this paper, quantitative understanding of a frequency-domain nonlinearity indicator is developed. The indicator is derived from an ensemble-averaged, frequency-domain version of the generalized Burgers equation, which can be rearranged in order to directly compare the effects of nonlinearity, absorption, and geometric spreading on the pressure spectrum level with frequency and distance. The nonlinear effect is calculated using pressure-squared-pressure quadspectrum. Further theoretical development has given an expression for the role of the normalized quadspectrum, referred to as Q/S by Morfey and Howell [AIAA J. 19, 986-992 (1981)], in the spatial rate of change of the pressure spectrum level. To explore this finding, an investigation of the change in level for initial sinusoids propagating as plane waves through inviscid and thermoviscous media has been conducted. The decibel change with distance, calculated through Q/S, captures the growth and decay of the harmonics and indicates that the most significant changes in level occur prior to sawtooth formation. At large distances, the inviscid case results in a spatial rate of change that is uniform across all harmonics. For thermoviscous media, large positive nonlinear gains are observed but offset by absorption, which leads to a greater overall negative spatial rate of change for higher harmonics. PMID- 27250147 TI - Compensation for a lip-tube perturbation in 4-year-olds: Articulatory, acoustic, and perceptual data analyzed in comparison with adults. AB - The nature of the speech goal in children was investigated in a study of compensation strategies for a lip-tube perturbation. Acoustic, articulatory, and perceptual analyses of the vowels /y/ and /u/ produced by ten 4-year-old French speakers and ten adult French speakers were conducted under two conditions: normal and with a large tube inserted between the lips. Ultrasound and acoustic recordings of isolated vowels were made in the normal condition before any perturbation, for each of the trials in the perturbed condition, and in the normal condition after the perturbed trials. Data revealed that adult participants moved their tongues in the perturbed condition more than children did. The perturbation was generally at least partly compensated for during the perturbed trials in adults, but children did not show a typical learning effect. In particular, unsystematic improvements were observed during the sequence of perturbed trials, and after-effects were not clear in the articulatory domain. This suggests that children may establish associative links between multisensory phonemic representations and articulatory maneuvers, but those links may mainly rely on trial-to-trial, error-based feedback correction mechanisms rather than on the internal model of the speech production apparatus, as they are in adults. PMID- 27250148 TI - Automatic grunt detector and recognizer for Atlantic cod (Gadus morhua). AB - Northwest Atlantic cod (Gadus morhua) have been heavily overfished in recent years and have not yet recovered. Passive acoustic technology offers a new approach to identify the spatial location of spawning fish, as well as their seasonal and long term persistence in an area. To date, the lack of a species specific detector has made searching for Atlantic cod grunts in large amounts of passive acoustic data cumbersome. To address this problem, an automatic grunt detection and recognition algorithm that processes yearlong passive acoustic data recordings was designed. The proposed technique is a two-stage hypothesis testing algorithm that includes detecting and recognizing all grunt-like sounds. Test results demonstrated that the algorithm provided a detection probability of 0.93 for grunts with a signal-to-noise ratio (SNR) higher than 10 dB, and a detection probability of 0.8 for grunts with the SNR ranging from 3 to 10 dB. This detector is being used to identify cod in current and historical data from U.S. waters. Its use has significantly reduced the time required to find and validate the presence of cod grunts. PMID- 27250149 TI - Phonetic correlates of phonological vowel quantity in Yakut read and spontaneous speech. AB - The quantity language Yakut (Sakha) has a binary distinction between short and long vowels. Disyllabic words with short and long vowels in one or both syllables were extracted from spontaneous speech of native Yakut speakers. In addition, a controlled production by a native speaker of disyllabic words with different short and long vowel combinations along with contrastive minimal pairs was recorded in a phonetics laboratory. Acoustic measurements of the vowels' fundamental frequency, duration, and intensity showed a significant consistent lengthening of phonologically long vowels compared to their short counterparts. However, in addition to evident durational differences between long and short quantities, fundamental frequency and intensity also showed effects of quantity. These results allow the interpretation that similarly to other non-tonal quantity languages like Finnish or Estonian, the Yakut vowel quantity opposition is not based exclusively on durational differences. The data furthermore revealed differences in F0 contours between spontaneous and read speech, providing some first indications of utterance-level prosody in Yakut. PMID- 27250150 TI - Characterization of compressed earth blocks using low frequency guided acoustic waves. AB - The objective of this work was to analyze the influence of compaction pressure on the intrinsic acoustic parameters (porosity, tortuosity, air-flow resistivity, viscous, and thermal characteristic lengths) of compressed earth blocks through their identification by solving an inverse acoustic wave transmission problem. A low frequency acoustic pipe (60-6000 Hz of length 22 m, internal diameter 3.4 cm) was used for the experimental characterization of the samples. The parameters were identified by the minimization of the difference between the transmissions coefficients data obtained in the pipe with that from an analytical interaction model in which the compressed earth blocks were considered as having rigid frames. The viscous and thermal effects in the pores were accounted for by employing the Johnson-Champoux-Allard-Lafarge model. The results obtained by inversion for high-density compressed earth blocks showed some discordance between the model and experiment especially for the high frequency limit of the acoustic characteristics studied. This was as a consequence of applying high compaction pressure rendering them very highly resistive therefore degrading the signal-to-noise ratios of the transmitted waves. The results showed that the airflow resistivity was very sensitive to the degree of the applied compaction pressure used to form the blocks. PMID- 27250151 TI - Nonlinear cochlear mechanics. AB - An earlier paper characterizing the linear mechanical response of the organ of Corti [J. Acoust. Soc. Am. 138, 1102-1121 (2015)] is extended to the nonlinear domain. Assuming the existence of nonlinear oscillators nonlocally coupled through the pressure they help create, the oscillator equations are derived and examined when the stimuli are modulated tones and clicks. The nonlinearities are constrained by the requirements of oscillator stability and the invariance of zero crossings in the click response to changes in click amplitude. The nonlinear oscillator equations for tones are solved in terms of the fluid pressure that drives them, and its time derivative, presumably a proxy for forces created by outer hair cells. The pressure equation is reduced to quadrature, the integrand depending on the oscillators' responses. The resulting nonlocally coupled nonlinear equations for the pressure, and oscillator amplitudes and phases, are solved numerically in terms of the fluid pressure at the stapes. Methods for determining the nonlinear damping directly from measurements are described. Once the oscillators have been characterized from their tone and click responses, the mechanical response of the cochlea to natural sounds may be computed numerically. Signal processing inspired by cochlear mechanics opens up a new area of nonlocal nonlinear time-frequency analysis. PMID- 27250152 TI - Can the elongated hindwing tails of fluttering moths serve as false sonar targets to divert bat attacks? AB - It has long been postulated that the elongated hindwing tails of many saturniid moths have evolved to create false sonar targets to divert the attack of echolocation-guided bat predators. However, rigorous echo-acoustic evidence to support this hypothesis has been lacking. In this study, fluttering luna moths (Actias luna), a species with elongated hindwing tails, were ensonified with frequency modulated chirp signals from all angles of orientation and across the wingbeat cycle. High-speed stereo videography was combined with pulse compression sonar processing to characterize the echo information available to foraging bats. Contrary to previous suggestions, the results show that the tail echoes are weak and do not dominate the sonar returns, compared to the large, planar wings and the moth body. However, the distinctive twisted morphology of the tails create persistent echoes across all angles of orientation, which may induce erroneous sonar target localization and disrupt accurate tracking by echolocating bats. These findings thus suggest a refinement of the false target hypothesis to emphasize sonar localization errors induced by the twisted tails, and highlight the importance of physics-based approaches to study the sensory information involved in the evolutionary arms race between moths and their bat predators. PMID- 27250153 TI - The multiple contributions of interaural differences to improved speech intelligibility in multitalker scenarios. AB - Spatial separation of talkers is known to improve speech intelligibility in a multitalker scenario. A contribution of binaural unmasking, in addition to a better-ear effect, is usually considered to account for this advantage. Binaural unmasking is assumed to result from the spectro-temporally simultaneous presence of target and masker energy with different interaural properties. However, in the case of speech targets and speech interference, the spectro-temporal signal-to noise ratio (SNR) fluctuates strongly, resulting in audible and localizable glimpses of target speech even at adverse global SNRs. The disparate interaural properties of target and masker may thus lead to improved segregation without requiring simultaneity. This study addresses the binaural contribution to spatial release from masking due to simultaneous disparities in interaural cues between target and interferers. For that purpose stimuli were designed that lacked simultaneously occurring disparities, but yielded a percept of spatially separated speech nearly indistinguishable from that of non-modified stimuli. A phoneme recognition experiment with either three collocated or spatially separated talkers showed a substantial spatial release from masking for the modified stimuli. The results suggest that binaural unmasking made a minor contribution to spatial release from masking, and that rather the interaural cues mediated by dominant speech components were essential. PMID- 27250154 TI - Large-scale training to increase speech intelligibility for hearing-impaired listeners in novel noises. AB - Supervised speech segregation has been recently shown to improve human speech intelligibility in noise, when trained and tested on similar noises. However, a major challenge involves the ability to generalize to entirely novel noises. Such generalization would enable hearing aid and cochlear implant users to improve speech intelligibility in unknown noisy environments. This challenge is addressed in the current study through large-scale training. Specifically, a deep neural network (DNN) was trained on 10 000 noises to estimate the ideal ratio mask, and then employed to separate sentences from completely new noises (cafeteria and babble) at several signal-to-noise ratios (SNRs). Although the DNN was trained at the fixed SNR of - 2 dB, testing using hearing-impaired listeners demonstrated that speech intelligibility increased substantially following speech segregation using the novel noises and unmatched SNR conditions of 0 dB and 5 dB. Sentence intelligibility benefit was also observed for normal-hearing listeners in most noisy conditions. The results indicate that DNN-based supervised speech segregation with large-scale training is a very promising approach for generalization to new acoustic environments. PMID- 27250155 TI - A meshless method for unbounded acoustic problems. AB - In this paper an effective meshless method is proposed to solve time-harmonic acoustic problems defined on unbounded domains. To this end, the near field is discretized by a set of nodes and the far field effect is taken into account by considering radiative boundary conditions. The approximation within the near field is performed using a set of local residual-free basis functions defined on a series of finite clouds. For considering the far field effect, a series of infinite clouds are defined on which another set of residual-free bases, satisfying the radiation conditions, are considered for the approximation. Validation of the results is performed through solving some acoustic problems. PMID- 27250157 TI - Analysis of coupled fast-shear and extensional vibrations of a LiTaO3 crystal plate with a ferroelectric inversion layer. AB - The resonance vibrations of LiTaO3 fast-shear overtone mode resonators with a ferroelectric inversion layer are analyzed. In addition to the fast-shear mode, the coupled extensional mode is considered. Different from most of the LiTaO3 resonators studied in the literature that are based on the slow-shear mode, the resonator in this paper operates with the fast-shear overtone mode. Results show that the capacitance ratio assumes maxima at two resonances, which are identified to be the second overtone modes of fast-shear and extension, respectively. It is found that the thickness of the inversion layer has obvious influences on the capacitance ratio of fast-shear and extensional modes. This condition may provide a simple method to adjust capacitance ratios of piezoelectric resonators. The influence mechanisms are also discussed. Besides, the effect of the cut angle of the crystal on the mode shape of vibrations is also investigated. The results can be used as important basis of parameters designs of LiTaO3 resonators operating on the fast-shear overtone mode. PMID- 27250156 TI - Experimental validation of a nonlinear derating technique based upon Gaussian modal representation of focused ultrasound beams. AB - A technique useful for performing derating at acoustic powers where significant harmonic generation occurs is illustrated and validated with experimental measurements. The technique was previously presented using data from simulations. The method is based upon a Gaussian representation of the propagation modes, resulting in simple expressions for the modal quantities, but a Gaussian source is not required. The nonlinear interaction of modes within tissue is estimated from the nonlinear interaction in water, using appropriate amounts of source reduction and focal-point reduction derived from numerical simulations. An important feature of this nonlinear derating method is that focal temperatures can be estimated with little additional effort beyond that required to determine the focal pressure waveforms. Hydrophone measurements made in water were used to inform the derating algorithm, and the resulting pressure waveforms and increases in temperature were compared with values directly measured in tissue phantoms. For a 1.05 MHz focused transducer operated at 80 W and 128 W, the derated pressures (peak positive, peak negative) agreed with the directly measured values to within 11%. Focal temperature rises determined by the derating method agreed with values measured using a remote thermocouple technique with a difference of 17%. PMID- 27250158 TI - Comparisons between physics-based, engineering, and statistical learning models for outdoor sound propagation. AB - Many outdoor sound propagation models exist, ranging from highly complex physics based simulations to simplified engineering calculations, and more recently, highly flexible statistical learning methods. Several engineering and statistical learning models are evaluated by using a particular physics-based model, namely, a Crank-Nicholson parabolic equation (CNPE), as a benchmark. Narrowband transmission loss values predicted with the CNPE, based upon a simulated data set of meteorological, boundary, and source conditions, act as simulated observations. In the simulated data set sound propagation conditions span from downward refracting to upward refracting, for acoustically hard and soft boundaries, and low frequencies. Engineering models used in the comparisons include the ISO 9613-2 method, Harmonoise, and Nord2000 propagation models. Statistical learning methods used in the comparisons include bagged decision tree regression, random forest regression, boosting regression, and artificial neural network models. Computed skill scores are relative to sound propagation in a homogeneous atmosphere over a rigid ground. Overall skill scores for the engineering noise models are 0.6%, -7.1%, and 83.8% for the ISO 9613-2, Harmonoise, and Nord2000 models, respectively. Overall skill scores for the statistical learning models are 99.5%, 99.5%, 99.6%, and 99.6% for bagged decision tree, random forest, boosting, and artificial neural network regression models, respectively. PMID- 27250160 TI - Editorial-A brief journal status update. AB - In this editorial, the Editor-in-Chief of the Journal of the Acoustical Society of America gives a brief overview of the present status of the Journal, emphasizing the events that have occurred over the past one and one half years. Topics addressed include: (1) The recent transition to the Editorial Manager peer review system, (2) new features that have been implemented in the Journal, (3) the incoming Managing Editor, (4) the publications component of the Acoustical Society's Strategic Plan, (5) new and revived article types, (6) open access, and (7) Journal metrics and statistics. PMID- 27250159 TI - Observations and Bayesian location methodology of transient acoustic signals (likely blue whales) in the Indian Ocean, using a hydrophone triplet. AB - A notable sequence of calls was encountered, spanning several days in January 2003, in the central part of the Indian Ocean on a hydrophone triplet recording acoustic data at a 250 Hz sampling rate. This paper presents signal processing methods applied to the waveform data to detect, group, extract amplitude and bearing estimates for the recorded signals. An approximate location for the source of the sequence of calls is inferred from extracting the features from the waveform. As the source approaches the hydrophone triplet, the source level (SL) of the calls is estimated at 187 +/- 6 dB re: 1 MUPa-1 m in the 15-60 Hz frequency range. The calls are attributed to a subgroup of blue whales, Balaenoptera musculus, with a characteristic acoustic signature. A Bayesian location method using probabilistic models for bearing and amplitude is demonstrated on the calls sequence. The method is applied to the case of detection at a single triad of hydrophones and results in a probability distribution map for the origin of the calls. It can be extended to detections at multiple triads and because of the Bayesian formulation, additional modeling complexity can be built-in as needed. PMID- 27250161 TI - Elastic parabolic equation and normal mode solutions for seismo-acoustic propagation in underwater environments with ice covers. AB - Sound propagation predictions for ice-covered ocean acoustic environments do not match observational data: received levels in nature are less than expected, suggesting that the effects of the ice are substantial. Effects due to elasticity in overlying ice can be significant enough that low-shear approximations, such as effective complex density treatments, may not be appropriate. Building on recent elastic seafloor modeling developments, a range-dependent parabolic equation solution that treats the ice as an elastic medium is presented. The solution is benchmarked against a derived elastic normal mode solution for range-independent underwater acoustic propagation. Results from both solutions accurately predict plate flexural modes that propagate in the ice layer, as well as Scholte interface waves that propagate at the boundary between the water and the seafloor. The parabolic equation solution is used to model a scenario with range dependent ice thickness and a water sound speed profile similar to those observed during the 2009 Ice Exercise (ICEX) in the Beaufort Sea. PMID- 27250163 TI - Dual instrument passive acoustic monitoring of belugas in Cook Inlet, Alaska. AB - As part of a long-term research program, Cook Inlet beluga (Delphinapterus leucas) presence was acoustically monitored with two types of acoustic sensors utilized in tandem in moorings deployed year-round: an ecological acoustic recorder (EAR) and a cetacean and porpoise detector (C-POD). The EAR was used primarily to record the calls, whistles, and buzzes produced by belugas and killer whales (Orcinus orca). The C-POD was used to log and classify echolocation clicks from belugas, killer whales, and porpoises. This paper describes mooring packages that maximized the chances of successful long-term data collection in the particularly challenging Cook Inlet environment, and presents an analytical comparison of odontocete detections obtained by the collocated EAR and C-POD instruments from two mooring locations in the upper inlet. Results from this study illustrate a significant improvement in detecting beluga and killer whale presence when the different acoustic signals detected by EARs and C-PODs are considered together. Further, results from concurrent porpoise detections indicating prey competition and feeding interference with beluga, and porpoise displacement due to ice formation are described. PMID- 27250162 TI - Non-stationary Bayesian estimation of parameters from a body cover model of the vocal folds. AB - The evolution of reduced-order vocal fold models into clinically useful tools for subject-specific diagnosis and treatment hinges upon successfully and accurately representing an individual patient in the modeling framework. This, in turn, requires inference of model parameters from clinical measurements in order to tune a model to the given individual. Bayesian analysis is a powerful tool for estimating model parameter probabilities based upon a set of observed data. In this work, a Bayesian particle filter sampling technique capable of estimating time-varying model parameters, as occur in complex vocal gestures, is introduced. The technique is compared with time-invariant Bayesian estimation and least squares methods for determining both stationary and non-stationary parameters. The current technique accurately estimates the time-varying unknown model parameter and maintains tight credibility bounds. The credibility bounds are particularly relevant from a clinical perspective, as they provide insight into the confidence a clinician should have in the model predictions. PMID- 27250164 TI - A simulation framework for auditory discrimination experiments: Revealing the importance of across-frequency processing in speech perception. AB - A framework for simulating auditory discrimination experiments, based on an approach from Schadler, Warzybok, Hochmuth, and Kollmeier [(2015). Int. J. Audiol. 54, 100-107] which was originally designed to predict speech recognition thresholds, is extended to also predict psychoacoustic thresholds. The proposed framework is used to assess the suitability of different auditory-inspired feature sets for a range of auditory discrimination experiments that included psychoacoustic as well as speech recognition experiments in noise. The considered experiments were 2 kHz tone-in-broadband-noise simultaneous masking depending on the tone length, spectral masking with simultaneously presented tone signals and narrow-band noise maskers, and German Matrix sentence test reception threshold in stationary and modulated noise. The employed feature sets included spectro temporal Gabor filter bank features, Mel-frequency cepstral coefficients, logarithmically scaled Mel-spectrograms, and the internal representation of the Perception Model from Dau, Kollmeier, and Kohlrausch [(1997). J. Acoust. Soc. Am. 102(5), 2892-2905]. The proposed framework was successfully employed to simulate all experiments with a common parameter set and obtain objective thresholds with less assumptions compared to traditional modeling approaches. Depending on the feature set, the simulated reference-free thresholds were found to agree with-and hence to predict-empirical data from the literature. Across-frequency processing was found to be crucial to accurately model the lower speech reception threshold in modulated noise conditions than in stationary noise conditions. PMID- 27250165 TI - Acoustic firearm discharge detection and classification in an enclosed environment. AB - Two different signal processing algorithms are described for detection and classification of acoustic signals generated by firearm discharges in small enclosed spaces. The first is based on the logarithm of the signal energy. The second is a joint entropy. The current study indicates that a system using both signal energy and joint entropy would be able to both detect weapon discharges and classify weapon type, in small spaces, with high statistical certainty. PMID- 27250166 TI - On the performance and flow characteristics of jet pumps with multiple orifices. AB - The design of compact thermoacoustic devices requires compact jet pump geometries, which can be realized by employing jet pumps with multiple orifices. The oscillatory flow through the orifice(s) of a jet pump generates asymmetric hydrodynamic end effects, which result in a time-averaged pressure drop that can counteract Gedeon streaming in traveling wave thermoacoustic devices. In this study, the performance of jet pumps having 1-16 orifices is characterized experimentally in terms of the time-averaged pressure drop and acoustic power dissipation. Upon increasing the number of orifices, a significant decay in the jet pump performance is observed. Further analysis shows a relation between this performance decay and the diameter of the individual holes. Possible causes of this phenomenon are discussed. Flow visualization is used to study the differences in vortex ring interaction from adjacent jet pump orifices. The mutual orifice spacing is varied and the corresponding jet pump performance is measured. The orifice spacing is shown to have less effect on the jet pump performance compared to increasing the number of orifices. PMID- 27250167 TI - Geometrical parameter combinations that correlate with early interaural cross correlation coefficients in a performance hall. AB - The previous binaural data of the authors measured inside two multi-purpose performance halls are re-analyzed using regression in this study. It is done in an attempt to establish a framework that can improve the prediction of early interaural cross-correlation coefficients (IACCs), but with as little measurement effort and parameters as possible. The results show that regression models consist of linear combinations of polynomials of geometrical parameters, when used together with the measurement schemes suggested previously by the authors, are sufficient for predicting the IACCs to within engineering tolerance. The predictions are better than those obtained previously by the neural network approach of the authors. The relative importance of the geometrical parameters in the prediction of IACCs is also investigated. PMID- 27250168 TI - Estimation of saxophone reed parameters during playing. AB - An approach for the estimation of single reed parameters during playing, using an instrumented mouthpiece and an iterative method, is presented. Different physical models describing the reed tip movement are tested in the estimation method. The uncertainties of the sensors installed on the mouthpiece and the limits of the estimation method are studied. A tenor saxophone reed is mounted on this mouthpiece connected to a cylinder, played by a musician, and characterized at different dynamic levels. Results show that the method can be used to estimate the reed parameters with a small error for low and medium sound levels (piano and mezzoforte dynamic levels). The analysis reveals that the complexity of the physical model describing the reed behavior must increase with dynamic levels. For medium level dynamics, the most relevant physical model assumes that the reed is an oscillator with non-linear stiffness and damping, the effect of mass (inertia) being very small. PMID- 27250169 TI - Radiation efficiency of plates subjected to turbulent boundary layer fluctuations. AB - The modal averaged radiation efficiency of a rectangular plate subjected to turbulent boundary layer fluctuations is discussed in this letter. Numerical results demonstrate that below the hydrodynamic coincidence frequency, the modal averaged radiation efficiency will be larger with the increase of the convection velocity, and an increase of the structural damping will increase the modal averaged radiation efficiency at sub-critical frequencies. PMID- 27250170 TI - Effects of noise, reverberation and foreign accent on native and non-native listeners' performance of English speech comprehension. AB - A large number of non-native English speakers may be found in American classrooms, both as listeners and talkers. Little is known about how this population comprehends speech in realistic adverse acoustical conditions. A study was conducted to investigate the effects of background noise level (BNL), reverberation time (RT), and talker foreign accent on native and non-native listeners' speech comprehension, while controlling for English language abilities. A total of 115 adult listeners completed comprehension tasks under 15 acoustic conditions: three BNLs (RC-30, RC-40, and RC-50) and five RTs (from 0.4 to 1.2 s). Fifty-six listeners were tested with speech from native English speaking talkers and 59 with native Mandarin-Chinese-speaking talkers. Results show that, while higher BNLs were generally more detrimental to listeners with lower English proficiency, all listeners experienced significant comprehension deficits above RC-40 with native English talkers. This limit was lower (i.e., above RC-30), however, with Chinese talkers. For reverberation, non-native listeners as a group performed best with RT up to 0.6 s, while native listeners performed equally well up to 1.2 s. A matched foreign accent benefit has also been identified, where the negative impact of higher reverberation does not exist for non-native listeners who share the talker's native language. PMID- 27250171 TI - Intensity statistics of very high frequency sound scattered from wind-driven waves. AB - The interaction of vhf 100-1000 kHz underwater sound with the ocean surface is explored. The bistatic forward scatter of 300 kHz sound is measured in a wind driven wave channel. Fluctuations in arrival amplitude are described by the scintillation index (SI) which is a measure of arrival intensity variance. SI initially increases with wind speed but eventually saturates to a value of 0.5 when the root-mean-square (rms) roughness is 0.5 mm. An adjusted scintillation index (SI*) is suggested that accounts for the multiple arrivals and properly saturates to a value of 1. Fluctuations in arrival time do not saturate and increase proportionately to the dominant surface wave component. Forward scattering is modeled at frequencies ranging from 50 to 2000 kHz using the Helmholtz-Kirchhoff integral with surface wave realizations derived from wave gauge data. The amplitude and temporal statistics of the simulated scattering agree well with measured data. Intensity saturation occurs at lower wind speeds for higher frequency sound. Both measured and modeled vhf sound is characterized by many surface arrivals at saturation. Doppler shifts associated with wave motion are expected to vary rapidly for vhf sound however further analysis is required. PMID- 27250172 TI - Supersonic intensity and non-negative intensity for prediction of radiated sound. AB - Two numerical methods to identify the surface areas of a vibrating structure that radiate sound are presented. The supersonic intensity identifies only the supersonic wave components of the sound field contributing to far-field radiated sound. The supersonic intensity is calculated using a two-dimensional convolution between a spatial radiation filter and the sound field. To compute the spatial radiation filter, the shortest surface distance between two points on the structure is calculated using the geodesic distance method. The non-negative intensity is based on acoustic radiation modes and identifies the radiated sound power from a vibrating structure. Numerical models of a baffled plate, a cylinder and an engine crankcase are presented. The supersonic intensity is shown to be difficult to implement at low frequencies due to the size of the spatial radiation filter and accuracy of the surface distances. A cut-off coefficient associated with the acoustic wavenumber of the spatial radiation filter is used to reduce the aperture error. A comparison of the two intensity-based techniques both in terms of a sound power ratio and the modal assurance criterion is introduced to identify the optimal values of the cut-off coefficients that result in better convergence between the intensity techniques. PMID- 27250173 TI - Optimized sound diffusers based on sonic crystals using a multiobjective evolutionary algorithm. AB - Sonic crystals have been demonstrated to be good candidates to substitute for conventional diffusers in order to overcome the need for extremely thick structures when low frequencies have to be scattered, however, their performance is limited to a narrow band. In this work, multiobjective evolutionary algorithms are used to extend the bandwidth to the whole low frequency range. The results show that diffusion can be significantly increased. Several cost functions are considered in the paper, on the one hand to illustrate the flexibility of the optimization and on the other hand to demonstrate the problems associated with the use of certain cost functions. A study of the robustness of the optimized diffusers is also presented, introducing a parameter that can help to choose among the best candidates. Finally, the advantages of the use of multiobjective optimization in comparison with conventional optimizations are discussed. PMID- 27250174 TI - Design and analysis of air acoustic vector-sensor configurations for two dimensional geometry. AB - Acoustic vector-sensors (AVS) have been designed using the P-P method for different microphone configurations. These configurations have been used to project the acoustic intensity on the orthogonal axes through which the direction of arrival (DoA) of a sound source has been estimated. The analytical expressions for the DoA for different microphone configurations have been derived for two dimensional geometry. Finite element method simulation using COMSOL-Multiphysics has been performed, where the microphone signals for AVS configurations have been recorded in free field conditions. The performance of all the configurations has been evaluated with respect to angular error and root-mean-square angular error. The simulation results obtained with ideal geometry for different configurations have been corroborated experimentally with prototype AVS realizations and also compared with microphone-array method, viz., Multiple Signal Classification and Generalized Cross Correlation. Experiments have been performed in an anechoic room using different prototype AVS configurations made from small size microphones. The DoA performance using analytical expressions, simulation studies, and experiments with prototype AVS in anechoic chamber are presented in the paper. The square and delta configurations are found to perform better in the absence and presence of noise, respectively. PMID- 27250175 TI - Kurtosis of room impulse responses as a diffuseness measure for reverberation chambers. AB - This study presents a kurtosis analysis of room impulse responses as a potential room diffuseness measure. The early part of an impulse response contains a direct sound and strong reflections. As these reflections are sparse and strong, the sound field is unlikely to be diffuse. Such deterministic reflections are extreme events, which prevent the pressure samples from being distributed Gaussianly, leading to a high kurtosis. This indicates that the kurtosis can be used as a diffuseness measure. Two rooms are analyzed. A non-uniform surface absorption distribution tends to increase the kurtosis significantly in a small room. A full scale reverberation chamber is tested with different diffuser settings, which shows that the kurtosis calculated from broadband impulse responses from 125 Hz to 4 kHz has a good correlation with the Sabine absorption coefficient according to ISO 354 (International Organization for Standardization, Geneva, Switzerland, 2003). PMID- 27250176 TI - Pile driving playback sounds and temporary threshold shift in harbor porpoises (Phocoena phocoena): Effect of exposure duration. AB - High intensity underwater sounds may cause temporary hearing threshold shifts (TTSs) in harbor porpoises, the magnitude of which may depend on the exposure duration. After exposure to playbacks of pile driving sounds, TTSs in two porpoises were quantified at 4 and 8 kHz with a psychophysical technique. At 8 kHz, the pile driving sounds caused the highest TTS. Pile driving sounds had the following: pulse duration 124 ms, rate 2760 strikes/h, inter-pulse interval 1.3 s, duty cycle ~9.5%, average received single-strike unweighted broadband sound exposure level (SELss) 145 dB re 1 MUPa(2)s, exposure duration range 15-360 min (cumulative SEL range: 173-187 dB re 1 MUPa(2)s). Control sessions were also carried out. Mean TTS (1-4 min after sound exposure stopped in one porpoise, and 12-16 min in the other animal) increased from 0 dB after 15 min exposure to 5 dB after 360 min exposure. Recovery occurred within 60 min post-exposure. For the signal duration, sound pressure level (SPL), and duty cycle used, the TTS onset SELcum is estimated to be around 175 dB re 1 MUPa(2)s. The small increase in TTS between 15 and 360 min exposures is due to the small amount of sound energy per unit of time to which the porpoises were exposed [average (over time) broadband SPL ~144 dB re 1 MUPa]. PMID- 27250177 TI - Influence of lips on the production of vowels based on finite element simulations and experiments. AB - Three-dimensional (3-D) numerical approaches for voice production are currently being investigated and developed. Radiation losses produced when sound waves emanate from the mouth aperture are one of the key aspects to be modeled. When doing so, the lips are usually removed from the vocal tract geometry in order to impose a radiation impedance on a closed cross-section, which speeds up the numerical simulations compared to free-field radiation solutions. However, lips may play a significant role. In this work, the lips' effects on vowel sounds are investigated by using 3-D vocal tract geometries generated from magnetic resonance imaging. To this aim, two configurations for the vocal tract exit are considered: with lips and without lips. The acoustic behavior of each is analyzed and compared by means of time-domain finite element simulations that allow free field wave propagation and experiments performed using 3-D-printed mechanical replicas. The results show that the lips should be included in order to correctly model vocal tract acoustics not only at high frequencies, as commonly accepted, but also in the low frequency range below 4 kHz, where plane wave propagation occurs. PMID- 27250178 TI - Sperm whale codas may encode individuality as well as clan identity. AB - Sperm whales produce codas for communication that can be grouped into different types according to their temporal patterns. Codas have led researchers to propose that sperm whales belong to distinct cultural clans, but it is presently unclear if they also convey individual information. Coda clicks comprise a series of pulses and the delay between pulses is a function of organ size, and therefore body size, and so is one potential source of individual information. Another potential individual-specific parameter could be the inter-click intervals within codas. To test whether these parameters provide reliable individual cues, stereo hydrophone acoustic tags (Dtags) were attached to five sperm whales of the Azores, recording a total of 802 codas. A discriminant function analysis was used to distinguish 288 5 Regular codas from four of the sperm whales and 183 3 Regular codas from two sperm whales. The results suggest that codas have consistent individual features in their inter-click intervals and inter-pulse intervals which may contribute to individual identification. Additionally, two whales produced different coda types in distinct foraging dive phases. Codas may therefore be used by sperm whales to convey information of identity as well as activity within a social group to a larger extent than previously assumed. PMID- 27250179 TI - Effects of speech style, room acoustics, and vocal fatigue on vocal effort. AB - Vocal effort is a physiological measure that accounts for changes in voice production as vocal loading increases. It has been quantified in terms of sound pressure level (SPL). This study investigates how vocal effort is affected by speaking style, room acoustics, and short-term vocal fatigue. Twenty subjects were recorded while reading a text at normal and loud volumes in anechoic, semi reverberant, and reverberant rooms in the presence of classroom babble noise. The acoustics in each environment were modified by creating a strong first reflection in the talker position. After each task, the subjects answered questions addressing their perception of the vocal effort, comfort, control, and clarity of their own voice. Variation in SPL for each subject was measured per task. It was found that SPL and self-reported effort increased in the loud style and decreased when the reflective panels were present and when reverberation time increased. Self-reported comfort and control decreased in the loud style, while self reported clarity increased when panels were present. The lowest magnitude of vocal fatigue was experienced in the semi-reverberant room. The results indicate that early reflections may be used to reduce vocal effort without modifying reverberation time. PMID- 27250181 TI - Estimation of biological parameters of marine organisms using linear and nonlinear acoustic scattering model-based inversion methods. AB - The linear inversion commonly used in fisheries and zooplankton acoustics assumes a constant inversion kernel and ignores the uncertainties associated with the shape and behavior of the scattering targets, as well as other relevant animal parameters. Here, errors of the linear inversion due to uncertainty associated with the inversion kernel are quantified. A scattering model-based nonlinear inversion method is presented that takes into account the nonlinearity of the inverse problem and is able to estimate simultaneously animal abundance and the parameters associated with the scattering model inherent to the kernel. It uses sophisticated scattering models to estimate first, the abundance, and second, the relevant shape and behavioral parameters of the target organisms. Numerical simulations demonstrate that the abundance, size, and behavior (tilt angle) parameters of marine animals (fish or zooplankton) can be accurately inferred from the inversion by using multi-frequency acoustic data. The influence of the singularity and uncertainty in the inversion kernel on the inversion results can be mitigated by examining the singular values for linear inverse problems and employing a non-linear inversion involving a scattering model-based kernel. PMID- 27250182 TI - Physiological motivated transmission-lines as front end for loudness models. AB - The perception of loudness is strongly influenced by peripheral auditory processing, which calls for a physiologically correct peripheral auditory processing stage when constructing advanced loudness models. Most loudness models, however, rather follow a functional approach: a parallel auditory filter bank combined with a compression stage, followed by spectral and temporal integration. Such classical loudness models do not allow to directly link physiological measurements like otoacoustic emissions to properties of their auditory filterbank. However, this can be achieved with physiologically motivated transmission-line models (TLMs) of the cochlea. Here two active and nonlinear TLMs were tested as the peripheral front end of a loudness model. The TLMs are followed by a simple generic back end which performs integration of basilar membrane "excitation" across place and time to yield a loudness estimate. The proposed model approach reaches similar performance as other state-of-the-art loudness models regarding the prediction of loudness in sones, equal-loudness contours (including spectral fine structure), and loudness as a function of bandwidth. The suggested model provides a powerful tool to directly connect objective measures of basilar membrane compression, such as distortion product otoacoustic emissions, and loudness in future studies. PMID- 27250183 TI - Modeling of speech localization in a multi-talker mixture using periodicity and energy-based auditory features. AB - A recent study showed that human listeners are able to localize a short speech target simultaneously masked by four speech tokens in reverberation [Kopco, Best, and Carlile (2010). J. Acoust. Soc. Am. 127, 1450-1457]. Here, an auditory model for solving this task is introduced. The model has three processing stages: (1) extraction of the instantaneous interaural time difference (ITD) information, (2) selection of target-related ITD information ("glimpses") using a template matching procedure based on periodicity, spectral energy, or both, and (3) target location estimation. The model performance was compared to the human data, and to the performance of a modified model using an ideal binary mask (IBM) at stage (2). The IBM-based model performed similarly to the subjects, indicating that the binaural model is able to accurately estimate source locations. Template matching using spectral energy and using a combination of spectral energy and periodicity achieved good results, while using periodicity alone led to poor results. Particularly, the glimpses extracted from the initial portion of the signal were critical for good performance. Simulation data show that the auditory features investigated here are sufficient to explain human performance in this challenging listening condition and thus may be used in models of auditory scene analysis. PMID- 27250185 TI - Multiple scattering by infinitely long cylindrical glass inclusions in a saturated Biot porous medium of glass beads. AB - The resonance spectrum of sets of two to five infinitely long parallel cylindrical glass inclusions in a fluid saturated porous matrix of unconsolidated glass beads is investigated. The ratio of bead diameters to inclusion diameters is 1/5. The far field form functions and the related phase derivatives are calculated by using an exact multiple scattering formalism and by assuming that the porous medium obeys Biot's model. In order to validate this hypothesis, comparisons between theory and experiments are done in the special case of a fast incident wave on a set of two and three inclusions. PMID- 27250184 TI - Frequencies, bandwidths and magnitudes of vocal tract and surrounding tissue resonances, measured through the lips during phonation. AB - The frequencies, magnitudes, and bandwidths of vocal tract resonances are all important in understanding and synthesizing speech. High precision acoustic impedance spectra of the vocal tracts of 10 subjects were measured from 10 Hz to 4.2 kHz by injecting a broadband acoustic signal through the lips. Between 300 Hz and 4 kHz the acoustic resonances R (impedance minima measured through the lips) and anti-resonances R- (impedance maxima) associated with the first three voice formants, have bandwidths of ~50 to 90 Hz for men and ~70 to 90 Hz for women. These acoustic resonances approximate those of a smooth, dry, rigid cylinder of similar dimensions, except that their bandwidths indicate higher losses in the vocal tract. The lossy, inertive load and airflow caused by opening the glottis further increase the bandwidths observed during phonation. The vocal tract walls are not rigid and measurements show an acousto-mechanical resonance R0 ~ 20 Hz and anti-resonance R-0~200 Hz. These give an estimate of wall inertance consistent with an effective thickness of 1-2 cm and a wall stiffness of 2-4 kN m(-1). The non-rigidity of the tract imposes a lower limit of the frequency of the first acoustic resonance fR1 and the first formant F1. PMID- 27250186 TI - Short-term annoyance reactions to stationary and time-varying wind turbine and road traffic noise: A laboratory study. AB - Current literature suggests that wind turbine noise is more annoying than transportation noise. To date, however, it is not known which acoustic characteristics of wind turbines alone, i.e., without effect modifiers such as visibility, are associated with annoyance. The objective of this study was therefore to investigate and compare the short-term noise annoyance reactions to wind turbines and road traffic in controlled laboratory listening tests. A set of acoustic scenarios was created which, combined with the factorial design of the listening tests, allowed separating the individual associations of three acoustic characteristics with annoyance, namely, source type (wind turbine, road traffic), A-weighted sound pressure level, and amplitude modulation (without, periodic, random). Sixty participants rated their annoyance to the sounds. At the same A weighted sound pressure level, wind turbine noise was found to be associated with higher annoyance than road traffic noise, particularly with amplitude modulation. The increased annoyance to amplitude modulation of wind turbines is not related to its periodicity, but seems to depend on the modulation frequency range. The study discloses a direct link of different acoustic characteristics to annoyance, yet the generalizability to long-term exposure in the field still needs to be verified. PMID- 27250188 TI - Eliciting the most prominent perceived differences between microphones. AB - The attributes contributing to the differences perceived between microphones (when auditioning recordings made with those microphones) are not clear from previous research. Consideration of technical specifications and expert opinions indicated that recording five programme items with eight studio and two microelectromechanical system microphones could allow determination of the attributes related to the most prominent inter-microphone differences. Pairwise listening comparisons between the resulting 50 recordings, followed by multi dimensional scaling analysis, revealed up to 5 salient dimensions per programme item; 17 corresponding pairs of recordings were selected exemplifying the differences across those dimensions. Direct elicitation and panel discussions on the 17 pairs identified a hierarchy of 40 perceptual attributes. An attribute contribution experiment on the 31 lowest-level attributes in the hierarchy allowed them to be ordered by degree of contribution and showed brightness, harshness, and clarity to always contribute highly to perceived inter-microphone differences. This work enables the future development of objective models to predict these important attributes. PMID- 27250187 TI - Factors affecting the development of speech recognition in steady and modulated noise. AB - This study used a checkerboard-masking paradigm to investigate the development of the speech reception threshold (SRT) for monosyllabic words in synchronously and asynchronously modulated noise. In asynchronous modulation, masker frequencies below 1300 Hz were gated off when frequencies above 1300 Hz were gated on, and vice versa. The goals of the study were to examine development of the ability to use asynchronous spectro-temporal cues for speech recognition and to assess factors related to speech frequency region and audible speech bandwidth. A speech shaped noise masker was steady or was modulated synchronously or asynchronously across frequency. Target words were presented to 5-7 year old children or to adults. Overall, children showed higher SRTs and smaller masking release than adults. Consideration of the present results along with previous findings supports the idea that children can have particularly poor masked SRTs when the speech and masker spectra differ substantially, and that this may arise due to children requiring a wider speech bandwidth than adults for speech recognition. The results were also consistent with the idea that children are relatively poor in integrating speech cues when the frequency regions with the best signal-to noise ratios vary across frequency as a function of time. PMID- 27250189 TI - On the sampling criterion for structural radiation in fluid. AB - When experimentally investigating the sound radiating from vibrating structures the surface is discretised into elemental areas also referred to as patches in which the surface vibrations are considered uniform. In many cases the structural Nyquist criterion imposes very small patch sizes which turn the experimental analysis into an overwhelmingly elaborate and error-prone task. The possibility to use a coarse sampling scheme for the surface velocity can greatly enhance the practical feasibility of such experimental investigations. Here the special case of a simply supported baffled plate excited by a broadband point force is considered. It is shown that accurate approximations of the radiated power may be obtained well beyond the frequency limit imposed by the structural Nyquist sampling criterion, provided the complex-valued vibration field is averaged over each patch. This is due to the fact that the structural wave components with wavenumbers greater than the acoustic wavenumber tend to be averaged out, owing to the mutual canceling of areas which vibrate out-of-phase within each patch, leaving only those components that contribute significantly to the radiated sound. It turns out, however, that this canceling process is not complete and that an error is introduced by the spatial aliasing. An analytical expression is derived allowing one to quantify this error and to optimise the patch size given a desired accuracy level and frequency range for the assessment of the radiated power. The proposed sampling criterion not only allows one to significantly reduce the measurement efforts when the radiation of vibro-acoustic systems are experimentally investigated but can also be applied to reduce the size of numerical models for weakly coupled structural-acoustic systems. PMID- 27250190 TI - The role of spectral detail in the binaural transfer function on perceived externalization in a reverberant environment. AB - Individual binaural room impulse responses (BRIRs) were recorded at a distance of 1.5 m for azimuth angles of 0 degrees and 50 degrees in a reverberant room. Spectral details were reduced in either the direct or the reverberant part of the BRIRs by averaging the magnitude responses with band-pass filters. For various filter bandwidths, the modified BRIRs were convolved with broadband noise and listeners judged the perceived position of the noise when virtualized over headphones. Only reductions in spectral details of the direct part obtained with filter bandwidths broader than one equivalent rectangular bandwidth affected externalization. Reductions in spectral details of the reverberant part had only little influence on externalization. In both conditions, externalization was not as pronounced at 0 degrees as at 50 degrees . To characterize the auditory processes that may be involved in the perception of externalization, a quantitative model is proposed. The model includes an echo-suppression mechanism, a filterbank describing the frequency selectivity in the cochlea and a binaural stage that measures the deviations of the interaural level differences between the considered input and the unmodified input. These deviations, integrated across frequency, are then mapped to a value that corresponds to the perceived externalization. PMID- 27250192 TI - Acoustic scattering from phononic crystals with complex geometry. AB - This work introduces a formalism for computing external acoustic scattering from phononic crystals (PCs) with arbitrary exterior shape using a Bloch wave expansion technique coupled with the Helmholtz-Kirchhoff integral (HKI). Similar to a Kirchhoff approximation, a geometrically complex PC's surface is broken into a set of facets in which the scattering from each facet is calculated as if it was a semi-infinite plane interface in the short wavelength limit. When excited by incident radiation, these facets introduce wave modes into the interior of the PC. Incorporation of these modes in the HKI, summed over all facets, then determines the externally scattered acoustic field. In particular, for frequencies in a complete bandgap (the usual operating frequency regime of many PC-based devices and the requisite operating regime of the presented theory), no need exists to solve for internal reflections from oppositely facing edges and, thus, the total scattered field can be computed without the need to consider internal multiple scattering. Several numerical examples are provided to verify the presented approach. Both harmonic and transient results are considered for spherical and bean-shaped PCs, each containing over 100 000 inclusions. This facet formalism is validated by comparison to an existing self-consistent scattering technique. PMID- 27250191 TI - In-air hearing of a diving duck: A comparison of psychoacoustic and auditory brainstem response thresholds. AB - Auditory sensitivity was measured in a species of diving duck that is not often kept in captivity, the lesser scaup. Behavioral (psychoacoustics) and electrophysiological [the auditory brainstem response (ABR)] methods were used to measure in-air auditory sensitivity, and the resulting audiograms were compared. Both approaches yielded audiograms with similar U-shapes and regions of greatest sensitivity (2000-3000 Hz). However, ABR thresholds were higher than psychoacoustic thresholds at all frequencies. This difference was least at the highest frequency tested using both methods (5700 Hz) and greatest at 1000 Hz, where the ABR threshold was 26.8 dB higher than the behavioral measure of threshold. This difference is commonly reported in studies involving many different species. These results highlight the usefulness of each method, depending on the testing conditions and availability of the animals. PMID- 27250193 TI - Time-domain comparisons of power law attenuation in causal and noncausal time fractional wave equations. AB - The attenuation of ultrasound propagating in human tissue follows a power law with respect to frequency that is modeled by several different causal and noncausal fractional partial differential equations. To demonstrate some of the similarities and differences that are observed in three related time-fractional partial differential equations, time-domain Green's functions are calculated numerically for the power law wave equation, the Szabo wave equation, and for the Caputo wave equation. These Green's functions are evaluated for water with a power law exponent of y = 2, breast with a power law exponent of y = 1.5, and liver with a power law exponent of y = 1.139. Simulation results show that the noncausal features of the numerically calculated time-domain response are only evident very close to the source and that these causal and noncausal time-domain Green's functions converge to the same result away from the source. When noncausal time-domain Green's functions are convolved with a short pulse, no evidence of noncausal behavior remains in the time-domain, which suggests that these causal and noncausal time-fractional models are equally effective for these numerical calculations. PMID- 27250194 TI - Multifractal analysis of visualized room impulse response for detecting early reflections. AB - This paper describes an improved method for detecting early reflections in the initial part of the room impulse response using multifractals. The proposed method uses the two-dimensional multifractal analysis. The room impulse response is visualized as a spectrogram image which is then subjected to the multifractal analysis. The algorithm is based on describing local regularity in the image using distribution of Holder exponents. The time positions of the selected Holder exponents in the image are utilized in detecting early reflections. The obtained results show better efficiency of the proposed algorithm compared to the previous one-dimensional multifractal analysis based algorithm. PMID- 27250195 TI - A simple expression for sound attenuation due to surface duct energy leakage in low-latitude oceans. AB - This paper presents an expression for the attenuation of sound energy in an ocean surface duct due to energy leakage outside the duct. Dominant parameters determining the attenuation are the sound frequency and the surface duct thickness. The attenuation is found to be exponentially dependent on a scaled frequency that combines the two parameters. Data from experiments in low-latitude oceans with three different surface duct thicknesses are used to verify the exponential expression derived for the attenuation. PMID- 27250196 TI - Whistle comparison of four delphinid species in Southeastern Brazil. AB - The present study evaluates variations in frequency and duration parameters of whistles of four dolphin species (Sotalia guianensis, Steno bredanensis, Stenella frontalis, and Tursiops truncatus), recorded in the Rio de Janeiro State Coast, Southeastern Brazil. A total of 487 whistles were analyzed. Acoustic parameters of the whistles were classified to species by discriminant function analysis. Overall classification score was 72.5%, with the highest classification score obtained for whistles of S. bredanensis and the lowest obtained for S. frontalis. Most differences were among S. bredanensis and S. guianensis, species that did not have their repertoires compared in other studies. PMID- 27250197 TI - Gaps-in-noise detection and gender identification from noise-vocoded vowel segments: Comparing performance of active musicians to non-musicians. AB - This study evaluated performance on a gender identification and temporal resolution task among active musicians and age-matched non-musicians. Brief duration (i.e., 50 and 100 ms) vowel segments produced by four adult male and four adult female speakers were spectro-temporally degraded using various parameters and presented to both groups for gender identification. Gap detection thresholds were measured using the gaps-in-noise (GIN) test. Contrary to the stated hypothesis, a significant difference in gender identification was not observed between the musician and non-musician listeners. A significant difference, however, was observed on the temporal resolution task, with the musician group achieving approximately 2 ms shorter gap detection thresholds on the GIN test compared to the non-musician counterparts. These results provide evidence supporting the potential benefits of musical training on temporal processing abilities, which have implications for the processing of speech in degraded listening environments and the enhanced processing of the fine-grained temporal aspects of the speech signal. The results also support the GIN test as an instrument sensitive to temporal processing differences among active musicians and non-musicians. PMID- 27250198 TI - The microscale evolution of the erosion front of blood clots exposed to ultrasound stimulated microbubbles. AB - Serial two-photon microscopy of blood clots with fluorescently tagged fibrin networks was conducted during microbubble-mediated sonothrombolysis to examine the microscale evolution of the resulting erosion front. The development of a complex zonal erosion pattern was observed, comprised of a cell depleted layer of fibrin network overlying intact clot which then underwent progressive recession. The fibrin zone architecture was dependent on exposure conditions with 0.1 MPa causing no erosion, 0.39 MPa resulting in homogenous structure, and combination 0.39/0.96 MPa pulses forming large-scale tunnels. High speed imaging and Coulter counter data indicated the fibrin zone formation process involves the ejection of intact erythrocytes. PMID- 27250199 TI - Size-isolation of ultrasound-mediated phase change perfluorocarbon droplets using differential centrifugation. AB - Perfluorocarbon droplets that are capable of an ultrasound-mediated phase transition have applications in diagnostic and therapeutic ultrasound. Techniques to modify the droplet size distribution are of interest because of the size dependent acoustic response of the droplets. Differential centrifugation has been used to isolate specific sizes of microbubbles. In this work, differential centrifugation was employed to isolate droplets with diameters between 1 and 3 MUm and 2 and 5 MUm from an initially polydisperse distribution. Further, an empirical model was developed for predicting the droplet size distribution following differential centrifugation and to facilitate the selection of centrifugation parameters for obtaining desired size distributions. PMID- 27250200 TI - Low frequency sound attenuation in a flow duct using a thin slow sound material. AB - A thin subwavelength material that can be flush mounted in a duct and that gives an attenuation band at low frequencies in air flow channels is presented. To decrease the material thickness, the sound is slowed in the material using folded side branch tubes. The impedance of the material is compared to the optimal value given by the Cremer condition, which can differ greatly from the air characteristic impedance. Grazing flow on this material increases the losses at the interface between the flow and the material. PMID- 27250201 TI - A comparative study on the contour tracking algorithms in ultrasound tongue images with automatic re-initialization. AB - The feasibility of an automatic re-initialization of contour tracking is explored by using an image similarity-based method in the ultrasound tongue sequences. To this end, the re-initialization method was incorporated into current state-of-art tongue tracking algorithms, and a quantitative comparison was made between different algorithms by computing the mean sum of distances errors. The results demonstrate that with automatic re-initialization, the tracking error can be reduced from an average of 5-6 to about 4 pixels, a result obtained by using a large number of hand-labeled frames and similarity measurements to extract the contours, which results in improved performance. PMID- 27250202 TI - Auditory detection of non-speech and speech stimuli in noise: Native speech advantage. AB - Detection thresholds of Chinese vowels, Korean vowels, and a complex tone, with harmonic and noise carriers were measured in noise for Mandarin Chinese-native listeners. The harmonic index was calculated as the difference between detection thresholds of the stimuli with harmonic carriers and those with noise carriers. The harmonic index for Chinese vowels was significantly greater than that for Korean vowels and the complex tone. Moreover, native speech sounds were rated significantly more native-like than non-native speech and non-speech sounds. The results indicate that native speech has an advantage over other sounds in simple auditory tasks like sound detection. PMID- 27250204 TI - Lexically driven selective adaptation by ambiguous auditory stimuli occurs after limited exposure to adaptors. AB - Limited exposure to ambiguous auditory stimuli results in perceptual recalibration. When unambiguous stimuli are used instead, selective adaptation (SA) effects have been reported, even after few adaptor presentations. Crucially, selective adaptation by an ambiguous sound in biasing lexical contexts had previously been found only after massive adaptor repetition [Samuel (2001). Psychol. Sci. 12(4), 348-351]. The present study shows that extensive exposure is not necessary for lexically driven selective adaptation to occur. Lexically driven selective adaptation can arise after as few as nine adaptor presentations. Additionally, build-up course inspection reveals several parallelisms with the time course observed for SA with unambiguous stimuli. PMID- 27250203 TI - Indexing head movement during speech production using optical markers. AB - Optical marker tracking integrated with electromagnetic articulometry was used to assess the movement extent of various points on (a) forehead skin and (b) points on a head-mounted apparatus, relative to a fixed point just above the upper incisors, and to compare the accuracy of the two different approaches to indexing head position during speech production. Both methods can provide a satisfactory index of head position. If skin-affixed markers are used, a minimum of 4 is recommended. Locations for optimal marker placement are identified. PMID- 27250205 TI - Proteomic Analysis of the Spatio-temporal Based Molecular Kinetics of Acute Spinal Cord Injury Identifies a Time- and Segment-specific Window for Effective Tissue Repair. AB - Spinal cord injury (SCI) represents a major debilitating health issue with a direct socioeconomic burden on the public and private sectors worldwide. Although several studies have been conducted to identify the molecular progression of injury sequel due from the lesion site, still the exact underlying mechanisms and pathways of injury development have not been fully elucidated. In this work, based on OMICs, 3D matrix-assisted laser desorption ionization (MALDI) imaging, cytokines arrays, confocal imaging we established for the first time that molecular and cellular processes occurring after SCI are altered between the lesion proximity, i.e. rostral and caudal segments nearby the lesion (R1-C1) whereas segments distant from R1-C1, i.e. R2-C2 and R3-C3 levels coexpressed factors implicated in neurogenesis. Delay in T regulators recruitment between R1 and C1 favor discrepancies between the two segments. This is also reinforced by presence of neurites outgrowth inhibitors in C1, absent in R1. Moreover, the presence of immunoglobulins (IgGs) in neurons at the lesion site at 3 days, validated by mass spectrometry, may present additional factor that contributes to limited regeneration. Treatment in vivo with anti-CD20 one hour after SCI did not improve locomotor function and decrease IgG expression. These results open the door of a novel view of the SCI treatment by considering the C1 as the therapeutic target. PMID- 27250207 TI - Atypical Manifestations in Glut1 Deficiency Syndrome. AB - Glucose transporter type 1 deficiency syndrome is a genetically determined, treatable, neurologic disorder that is caused by an insufficient transport of glucose into the brain. It is caused by a mutation in the SCL2A1 gene, which is so far the only known to be associated with this condition. Glucose transporter type 1 deficiency syndrome consists of a wide clinical spectrum that usually presents with cognitive impairment, epilepsy, paroxysmal exercise-induced dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbance, and dyspraxia in different combinations. However, there are other clinical manifestations that we consider equally peculiar but that have so far been poorly described in literature. In this review, supported by a video contribution, we will accurately describe this type of clinical manifestation such as oculogyric crises, weakness, paroxysmal kinesigenic and nonkinesigenic dyskinesia in order to provide an additional instrument for a correct, rapid diagnosis. PMID- 27250206 TI - Structure of Complement C3(H2O) Revealed By Quantitative Cross-Linking/Mass Spectrometry And Modeling. AB - The slow but spontaneous and ubiquitous formation of C3(H2O), the hydrolytic and conformationally rearranged product of C3, initiates antibody-independent activation of the complement system that is a key first line of antimicrobial defense. The structure of C3(H2O) has not been determined. Here we subjected C3(H2O) to quantitative cross-linking/mass spectrometry (QCLMS). This revealed details of the structural differences and similarities between C3(H2O) and C3, as well as between C3(H2O) and its pivotal proteolytic cleavage product, C3b, which shares functionally similarity with C3(H2O). Considered in combination with the crystal structures of C3 and C3b, the QCMLS data suggest that C3(H2O) generation is accompanied by the migration of the thioester-containing domain of C3 from one end of the molecule to the other. This creates a stable C3b-like platform able to bind the zymogen, factor B, or the regulator, factor H. Integration of available crystallographic and QCLMS data allowed the determination of a 3D model of the C3(H2O) domain architecture. The unique arrangement of domains thus observed in C3(H2O), which retains the anaphylatoxin domain (that is excised when C3 is enzymatically activated to C3b), can be used to rationalize observed differences between C3(H2O) and C3b in terms of complement activation and regulation. PMID- 27250208 TI - The Dopamine Receptor D5 May Influence Age of Onset: An Exploratory Study on Indo Caucasoid ADHD Subjects. AB - The objective was to investigate contribution of the dopamine receptor 5 (DRD5) gene variants in the symptoms of attention-deficit/hyperactivity disorder (ADHD) probands since brain regions identified to be affected in these group of patients have higher expression of the DRD5 receptor. Out of 22 exonic variants, 19 were monomorphic in the Indo-Caucasoid individuals. rs6283 "C" and rs113828117 "A" exhibited significant higher occurrence in families with ADHD probands. Several haplotypes showed biased occurrence in the probands. Early and late onset groups exhibited significantly different genotypic frequencies. A new G>A substitution was observed in the control samples only. The late onset group exhibited higher scores for hyperactivity as compared to the early onset group. The authors infer that the age of onset of ADHD may at least partially be affected by DRD5 variants warranting further investigation on the role of DRD5 in the disease etiology. PMID- 27250209 TI - Detecting Single-Nucleotide Substitutions Induced by Genome Editing. AB - The detection of genome editing is critical in evaluating genome-editing tools or conditions, but it is not an easy task to detect genome-editing events-especially single-nucleotide substitutions-without a surrogate marker. Here we introduce a procedure that significantly contributes to the advancement of genome-editing technologies. It uses droplet digital polymerase chain reaction (ddPCR) and allele-specific hydrolysis probes to detect single-nucleotide substitutions generated by genome editing (via homology-directed repair, or HDR). HDR events that introduce substitutions using donor DNA are generally infrequent, even with genome-editing tools, and the outcome is only one base pair difference in 3 billion base pairs of the human genome. This task is particularly difficult in induced pluripotent stem (iPS) cells, in which editing events can be very rare. Therefore, the technological advances described here have implications for therapeutic genome editing and experimental approaches to disease modeling with iPS cells. PMID- 27250211 TI - Effects of Isha Hatha Yoga on Core Stability and Standing Balance. AB - Context * Isha Hatha yoga is a form of yoga practice that practitioners claim can improve health. Gaining a scientific understanding of its effects on health is a crucial step in claiming health benefits. Objective * The study intended to investigate the effects of Isha Hatha yoga on core stability and standing balance in healthy volunteers. Design * The research team designed a quasiexperimental study. Setting * The setting was at Isha Yoga Center at Isha Foundation in Coimbatore, India. Participants * Participants were individuals registered for a residential program providing training in Isha Hatha yoga at the Isha Yoga Center. Intervention * The training consisted of 21 d of training in Isha Hatha yoga, including Upa yoga, Surya Kriya, Angamardhana, Bhuta Suddhi, and asanas. Outcome Measures * The single-leg stork test and the plank test were conducted before and after the training. Results * Significant increases occurred in the standing-stork test scores on the right (P = .014) and left (P = .033) sides and in the plank test scores (P < .001). Conclusions * The current study concluded that healthy volunteers who underwent 21 d of training in Isha Hatha yoga showed significant improvements in core strength and balance. PMID- 27250210 TI - Using Digital Polymerase Chain Reaction to Detect Single-Nucleotide Substitutions Induced by Genome Editing. AB - This protocol is designed to detect single-nucleotide substitutions generated by genome editing in a highly sensitive and quantitative manner. It uses a combination of allele-specific hydrolysis probes and a new digital polymerase chain reaction (dPCR) technology called droplet digital PCR (ddPCR). ddPCR partitions a reaction into more than 10,000 nanoliter-scale water-in-oil droplets. As a result, each droplet contains only a few copies of the genome so that ddPCR is able to detect rare genome-editing events without missing them. PMID- 27250212 TI - Salutogenesis and the Monks of Athos, Greece: A Spiritual Health Promotion? AB - Context * A cohort of studies on secular populations has indicated the role that religiosity plays in psychological well-being. An increase in the participation in religious activity has been shown to have a positive correlation with beneficial mental health outcomes. Internationally, few studies exist regarding the sense of coherence (SOC) of monks. SOC is a health asset related to stress management skills. Objective * The study aimed to assess the SOC of monks who lived at Mount Athos, Greece, and to determine its correlation with demographic characteristics. Design * The type of design was a descriptive cross-sectional study using convenience sampling. Setting * The study took place at Mount Athos in 2 monasteries and 1 skete, which is an organized community that consists of several monastic huts that belong to a communal monastery. Participants * Of the 215 monks living in the 2 monasteries and the skete, 166 monks participated. Outcome Measures * Data were collected from May-August 2012, using a structured questionnaire that was divided into 2 parts: (1) a demographic section (8 items) and (2) the Sense of Coherence (SOC-13) survey. Results * The mean age of participants was 45.5 y +/- 13.0. Of the 166 monks participating, 139 (83.7 %) lived in communal monasteries, and the mean time of participation in monasticism was 18.4 +/- 12.1 y. The mean value on the SOC-13 scale was 65.7 +/- 6.5. According to the multiple regression analyses, the number of years in monasticism presented a positive correlation with the SOC score (beta = 0.12, SE = 0.04, P = .003), whereas the number of daily hours of sleep presented a negative correlation with the SOC score (beta = -1.34, SE = 0.50, P = .008). Conclusions * The monks seemed to have a strong SOC and, therefore, adequate stress management skills. Religious spirituality may help individuals in coping with daily life. More evidence-based studies need to be implemented to highlight the correlation between Orthodox Christian monasticism and SOC. PMID- 27250213 TI - Case Report: Outcomes of Feldenkrais Movements on Self-reported Cognitive Decline in Older Adults. AB - Context * A lack of cognitive health can limit a person's well-being and may compromise independent living. The potential for cognitive decline is a major concern for aging individuals. Regular physical activity has been shown to improve cognitive processes. However, functional limitations frequently prevent older adults from participating in conventional exercise programs. Given the gentle nature of mind-body exercises, interventions such as the Feldenkrais may provide an alternative. Objective * The study intended to investigate whether Feldenkrais lessons can offset cognitive decline among older adults. DESIGN: The study was a case series with 2 participants. Setting * The study took place in the wellness center of a retirement community. Participants * Participants were 2 female residents in the community, with self-reported cognitive challenges. Intervention * The Feldenkrais method awareness through movement (ATM) was used. The lessons were based on common Feldenkrais themes, such as the relationship between eye organization and body movement, coordination of muscles, breathing, and an exploration of the participants' habits. Outcome Measures * The Trail Making Test A (TMT-A) and Trail Making Tests B (TMT-B) were used to measure cognitive function at baseline and after the Feldenkrais intervention. Results * Both participants improved their performance on the TMT-A and TMT-B after completing the Feldenkrais intervention. Neither of the 2 participants reported any adverse events related to the lessons. Conclusion * The beneficial results warrant further research into the efficacy of Feldenkrais as complementary, alternative therapy for preserving cognitive function on a larger scale and in populations with diagnosed cognitive impairments. PMID- 27250214 TI - Obesity and atrial fibrillation: can adipokines help to solve this puzzle. PMID- 27250215 TI - Contemporary evaluation and management of lower extremity peripheral artery disease. AB - Peripheral artery disease (PAD) includes atherosclerosis of the aorta and lower extremities. Affecting a large segment of the population, PAD is associated with impaired functional capacity and reduced quality of life as well as an increased risk of stroke, myocardial infarction and cardiovascular death. The evaluation of PAD begins with the physical examination, incorporating non-invasive testing such as ankle-brachial indices to confirm the diagnosis. Therapeutic interventions are aimed at alleviating symptoms while preserving limb integrity and reducing overall cardiovascular risk. With this in mind, risk factor modification with exercise and medical therapy are the mainstays of treatment for many patients with PAD. Persistent symptoms or non-healing wounds should prompt more aggressive therapies with endovascular or surgical revascularisation. The following manuscript provides a comprehensive review on the contemporary evaluation and management of PAD. PMID- 27250216 TI - Ventricular arrhythmias and sudden cardiac death in adults with congenital heart disease. AB - Remarkable gains in survival have led to an unprecedented number of adults with congenital heart disease. Arrhythmias collectively comprise the most common complication encountered. Recognising the unique issues and challenges involved in managing arrhythmias in adults with congenital heart disease and the consequential decisions surrounding sudden death prevention, expert societies have proposed evidence-based recommendations. On the whole, acute ventricular arrhythmias are managed according to general cardiology guidelines, while taking into consideration congenital heart disease-specific issues, such as positioning of patches or paddles according to location of the heart. Implantable cardioverter-defibrillators (ICDs) are indicated for secondary prevention in patients with sustained ventricular tachycardia or resuscitated cardiac arrest in the absence of a reversible cause. Pharmacological therapy and catheter ablation can be effective in reducing recurrent ICD shocks. Risk-benefit assessment for primary prevention ICDs is a major challenge. Although a clearer picture has emerged of the high-risk patient with tetralogy of Fallot, ICD indications for those with systemic right ventricles or univentricular hearts remain contentious. Challenges to ICD implantation include obstructed veins, conduits and baffles, atrioventricular valve disease and intracardiac shunts. In selected patients, customised systems with epicardial and/or subcutaneous coils may represent a viable solution. Alternatively, the subcutaneous ICD is an attractive option for patients in whom transvenous access is not feasible or desirable and in whom bradycardia and antitachycardia pacing features are not essential. Continued advances in risk stratification and device technologies carry the potential to further improve efficacy and safety outcomes in this growing population of patients. PMID- 27250217 TI - Expression of EAP1 and CUX1 in the hypothalamus of female rats and relationship with KISS1 and GnRH. AB - Using a combination of high throughput and bioinformatics strategies, in combination with a system biology approach, a group of related genes including EAP1 and CUX1 whose expression increased at the time of female puberty were singled out from the hypothalamus of nonhuman primates and rats. It was hypothesized that EAP1 and CUX1 genes may be required for the timely initiation of female puberty by regulating the expression of KISS1 gene. Therefore, we measured the hypothalamic expression of EAP1 and CUX1 genes of female SD rats in mRNA and protein levels along with the numbers of respective immunoreactive cells at three different development stages (juvenile, early puberty and adult). Besides, we investigated the distribution of their immunoreactive cells. Although there was no changes in the mRNA levels of EAP1 and CUX1 in the hypothalamus during the different sexual development stages, the protein expression of EAP1 in the early-puberty group was significantly higher than that in the juvenile group. Moreover, we found that EAP1 and CUX1 genes were localized in neuronal nuclei. Both were prominent in cells of the the arcuate nucleus (ARC) of the rat hypothalamus which was also the main localization of KISS1 gene. Especially, CUX1 gene was co-expressed in the kisspeptin neurons. Furthermore, the number and percentage of EAP1 immunoreactive cells in the early-puberty group were both significantly more than the juvenile group. Above results indicate that EAP1 gene may be involved in the neuroendocrine control of female puberty in correlation with the kisspeptin signaling. PMID- 27250218 TI - Sucralose, an activator of the glucose-sensing receptor, increases ATP by calcium dependent and -independent mechanisms. AB - Sucralose is an artificial sweetener and activates the glucose-sensing receptor expressed in pancreatic beta-cells. Although sucralose does not enter beta-cells nor acts as a substrate for glucokinase, it induces a marked elevation of intracellular ATP ([ATP]c). The present study was conducted to identify the signaling pathway responsible for the elevation of [ATP]c induced by sucralose. Previous studies have shown that sucralose elevates cyclic AMP (cAMP), activates phospholipase C (PLC) and stimulates Ca(2+) entry by a Na(+)-dependent mechanism in MIN6 cells. The addition of forskolin induced a marked elevation of cAMP, whereas it did not affect [ATP]c. Carbachol, an activator of PLC, did not increase [ATP]c. In addition, activation of protein kinase C by dioctanoylglycerol did not affect [ATP]c. In contrast, nifedipine, an inhibitor of the voltage-dependent Ca(2+) channel, significantly reduced [ATP]c response to sucralose. Removal of extracellular Na(+) nearly completely blocked sucralose induced elevation of [ATP]c. Stimulation of Na(+) entry by adding a Na(+) ionophore monensin elevated [ATP]c. The monensin-induced elevation of [ATP]c was only partially inhibited by nifedipine and loading of BAPTA, both of which completely abolished elevation of [Ca(2+)]c. These results suggest that Na(+) entry is critical for the sucralose-induced elevation of [ATP]c. Both calcium dependent and -independent mechanisms are involved in the action of sucralose. PMID- 27250219 TI - The effectiveness of beauty care on self-rated health among community-dwelling older people. AB - AIM: The maintenance and improvement of self-rated health is important for prolonging healthy life expectancy in a well-aged society. In the present study, we examined the effectiveness of beauty care on self-rated health among community dwelling older people through a quasi- randomized controlled trial by propensity score matching (PSM). METHOD: One hundred twelve community-dwelling older people who were recruited from the local community, participated in a beauty care program that consisted of two training sessions per month for 3 months and daily enforcement of facial skin care (intervention group). Seven hundred fifty-nine participants who received a comprehensive geriatric assessment were treated as a control group. Sex, age, BMI, lifestyle habits, hand grip strength, walking speed, skeletal muscle mass, bone density, medical history and life function (Kihon Checklist) were matched by the PSM method. We compared the subjects' self rated health, depressive mood status (self-rating depression scale: SDS), and the frequency of going outdoors in the intervention and control groups before and after intervention. RESULTS: The improvements of SDS were significantly greater in the intervention group than in the control group. The self-rated health and the frequency of going outdoors were maintained in the intervention group but were significantly decreased in the control group. CONCLUSION: We conclude that beauty care is effective for maintaining and improving the self-rated health and depression status of community-dwelling older people and that it may help prolong healthy life expectancy. PMID- 27250220 TI - Factors related to the urination methods of elderly people with incontinence who require at-home nursing care. AB - OBJECTIVE: This study aimed to elucidate the urination status among elderly people with incontinence who require at-home nursing care as well as the status of their family caregivers, and to identify the factors related to their urination methods. METHODS: In the present study, questionnaires were distributed to 101 elderly subjects (n=101) and their caregivers. RESULTS: The most prevalent urination method was the collaboration of toilet and adult diapers (69, 68.8%).There was a significantly larger number of patients who used a toilet <4 times and who had a "moderate" amount of incontinence and patients who used toilet 4-8 times and had a "slight" amount of incontinence (p<0.05). We performed a multivariate logistic regression analysis using the stepwise method. We used 8 items from the responses of the elderly subjects and their caregivers that were identified as being independently associated with the urination method using the chi-squared test (or Fisher's exact probability test), with the urination method as the dependent variable. Among elderly people, the ability to use a toilet properly (p=0.004) and independent mobility (p=0.028) strongly influenced their use of a toilet for urination. Among caregivers, the influencing factor was not thinking that they have to use the toilet even though they are unable to urinate (p=0.027). CONCLUSION: The use of a toilet for urination by elderly people was influenced by their physical functions and by the caregivers' attitudes toward excretion-related nursing care. When providing urination assistance, it is important for caregivers to maintain the physical functions of the elderly by providing support when necessary. It is also important to assess the bladder function by, methods such, as measuring the amount of residual urine and cooperate with a physician. PMID- 27250221 TI - Clinical characteristics of patients aged 65 and older with newly developed type 1 diabetes: An analysis of elderly patients at our hospital. AB - AIM: We herein investigated the clinical features of elderly patients with newly developed type 1 diabetes with respect to onset age, frequency of islet associated antibodies, and other clinical markers. METHODS: One hundred and ninety-nine patients aged 65 and older with new-onset diabetes, who were admitted to our hospital between July 2000 and June 2013, were classified into 4 types of diabetes. In addition, 85 patients with newly diagnosed type 1A diabetes among all age ranges admitted during the same period were divided into two groups: a younger group (less than 65 years, n=71) and an elderly group (65 years and older, n=14). Clinical features including mode of onset, frequency of islet associated antibodies, and serum C-peptide (CPR) levels were compared between these groups. The elderly group was further divided into two age groups (less than 75 years, n=7; 75 years and older, n=7), and the frequency of autoantibodies was compared. RESULTS: The patients (n=199) were classified into type 1 (n=16, 8%), type 2 (n=155, 78%), pancreatic (n=22, 11%), and other type (n=6, 3%) diabetes. Between the younger and elderly groups with type 1 diabetes, no significant difference in the CPR levels, frequency of autoantibodies, or other clinical features were observed. Positivity for IA-2 antibody was higher in the younger group (53.5%) than in the elderly group (35.7%), however, it was also considerably high (57.1%) in the oldest age group (75 years and older). CONCLUSIONS: Type 1 diabetes may develop in the elderly, and an IA-2 antibody test may be useful for diagnosing type 1 diabetes in older patients. PMID- 27250222 TI - The prevalence of dementia in subacute myelo-optico-neuropathy (SMON) patients who underwent medical checkups. AB - AIM: Subacute myelo-optico-neuropathy (SMON) is a known adverse effect of clioquinol use; however, clioquinol dissolves beta-amyloid aggregation in Alzheimer's disease (AD). Therefore, we investigated the prevalence of dementia in SMON patients and whether past clioquinol use affected the current incidence of AD. METHODS: We included 647 SMON patients (195 men, 452 women; mean age 77.9 years) who had undergone medical checkups including the mini-mental state examination (MMSE) in 2012. Of them, 105 patients scored <=23 on the MMSE assessment. The presence/absence of dementia and disease backgrounds were obtained by a questionnaire. Then, using the medical checkup database, the correlation between the degree of severity when signs of SMON were at their worst and the concurrent presence or absence of AD at present was analyzed. RESULTS: In patients >=65 years of age, the estimated prevalence of dementia was approximately 10.9% (95% confidence interval: 7.9%-13.8%). The concurrent presence of AD at present was not correlated with the past degree of SMON severity when the SMON signs were at their worst. CONCLUSIONS: The 10.9% prevalence of dementia in SMON patients was lower than a previously reported 15% prevalence found in the general population. According to these results, we cannot draw a definitive conclusion regarding the preventive effect of clioquinol on AD. Additionally, the lack of association between the onset of AD and past severity of SMON precludes definitive conclusions on the relationship between concurrent presence of AD and past clioquinol use. PMID- 27250223 TI - Transcatheter aortic valve implantation in an elderly man with severe aortic stenosis and high surgical risk. AB - An 85-year-old man with severe aortic stenosis (transaortic peak velocity 4.4 m/s, mean gradient 46 mmHg and valve area 0.71 cm(2)) was admitted to our hospital due to mild exertional dyspnea (NYHA class II). He had received low-dose prednisolone (5 mg/day) plus tacrolimus hydrate (1.5 mg/day) for rheumatic arthritis and interstitial pneumonia. Although aortic valve replacement was indicated, he was considered at high risk to undergo open heart surgery because of reduced pulmonary function (FEV1.0%, 77.2%) and long-term treatment with immunosuppressive drugs. After a multidisciplinary heart team conference, the decision was made to perform transfemoral transcatheter aortic valve implantation (TAVI) using a SAPIEN XT 26 mm valve. TAVI was completed in 105 minutes without any complications. After the procedure, his symptom was improved and his activity of daily life was maintained, and he was ambulatory the next day. Aortic stenosis by degenerative calcification is becoming increasingly common as the Japanese population ages. TAVI has been used to treat patients with concomitant diseases and at high risk of open heart surgery. We herein report a case with rheumatic arthritis and interstitial pneumonia that underwent successful TAVI. PMID- 27250224 TI - The safety and effectiveness of earwax removal by nurse in cognitive impaired inpatients. PMID- 27250226 TI - [Not Available]. PMID- 27250225 TI - Research of carotid stenosis in the elderly aged 80 and over in mountain towns. PMID- 27250227 TI - [Not Available]. PMID- 27250228 TI - [Not Available]. PMID- 27250232 TI - Long-term occipital nerve stimulation for drug-resistant chronic cluster headache. AB - Introduction Chronic cluster headache is rare and some of these patients become drug-resistant. Occipital nerve stimulation has been successfully employed in open studies to treat chronic drug-resistant cluster headache. Data from large group of occipital nerve stimulation-treated chronic cluster headache patients with long duration follow-up are advantageous. Patients and methods Efficacy of occipital nerve stimulation has been evaluated in an experimental monocentric open-label study including 35 chronic drug-resistant cluster headache patients (mean age 42 years; 30 men; mean illness duration: 6.7 years). The primary end point was a reduction in number of daily attacks. Results After a median follow up of 6.1 years (range 1.6-10.7), 20 (66.7%) patients were responders (>=50% reduction in headache number per day): 12 (40%) responders showed a stable condition characterized by sporadic attacks, five responders had a 60-80% reduction in headache number per day and in the remaining three responders chronic cluster headache was transformed in episodic cluster headache. Ten (33.3%) patients were non-responders; half of these have been responders for a long period (mean 14.6 months; range 2-48 months). Battery depletion (21 patients 70%) and electrode migration (six patients - 20%) were the most frequent adverse events. Conclusions Occipital nerve stimulation efficacy is confirmed in chronic drug-resistant cluster headaches even after an exceptional long-term follow-up. Tolerance can occur years after improvement. PMID- 27250233 TI - Relationship between serum levels of VIP, but not of CGRP, and cranial autonomic parasympathetic symptoms: A study in chronic migraine patients. AB - Background Cranial autonomic parasympathetic symptoms (CAPS) appear in at least half of migraine patients theoretically as a result of the release of peptides by the trigemino-vascular system (TVS). Cranial pain pathways become sensitised by repeated episodes of TVS activation, leading to migraine chronification. Objective The objective of this article is to correlate the presence of CAPS with serum levels of vasoactive intestinal peptides (VIP) and calcitonin gene-related peptide (CGRP). Patients and methods Patients with chronic migraine (CM) were asked about the presence - during migraine attacks - of five CAPS, which were scored from 0 to 10 by using a quantitative scale. Serum VIP and CGRP levels were determined by ELISA. Results We interviewed 87 CM patients (82 females; mean age 44.7 +/- 10.6 years). Seventeen had no CAPS, while 70 reported at least one CAPS. VIP levels ranged from 20.8 to 668.2 pg/ml (mean 154.5 +/- 123.2). There was a significant positive correlation between scores in the CAPS scale and VIP levels (Spearman correlation coefficient = 0.227; p = 0.035). VIP levels were significantly higher in CM patients by at least one point in the scale vs those with 0 points ( p = 0.002). Analysing symptoms individually, VIP levels were numerically higher in those patients with symptoms, though they were significantly higher only in those patients with lacrimation vs those without it ( p = 0.013). There was no significant correlation between CGRP levels and the score in the CAPS scale. Conclusions Serum VIP, but not CGRP, levels seem to reflect the rate of activation of the parasympathetic arm of the TVS in migraine. PMID- 27250234 TI - Anxiety and depression in probable migraine: A population-based study. AB - Background Although probable migraine (PM) is common among headache sufferers, there is little knowledge of the prevalence and impacts of comorbid anxiety and depression in patients with PM. We assessed the prevalence and impact of anxiety and depression among PM sufferers in the general population. Methods We recruited Korean individuals aged 19-69 years via stratified random sampling and assessed headache type, anxiety, and depression among them using structured interviews. Results In a representative sample of 2695 individuals, 143 (5.3%) and 379 (14.1%) had migraine and PM, respectively. Fewer patients with PM had anxiety (17.7% vs. 30.1%, p = 0.002) and depression (8.7% vs. 16.8%, p = 0.007) compared to those with migraine. Prevalence of anxiety and depression was lower in people with PM than in those with migraine in univariable analysis, but insignificant after including headache intensity and headache frequency for adjustment. Headache frequency, headache intensity, and impact of headache were significantly higher among PM and migraine patients with anxiety and depression than among those without. Conclusions The prevalence of anxiety and depression was lower among individuals with PM compared to those with migraine. However, they were still prevalent and associated with an exacerbation of symptoms among individuals with PM. PMID- 27250235 TI - Pain modulation is affected differently in medication-overuse headache and chronic myofascial pain - A multimodal MRI study. AB - Background Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. Methods In this cross sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH ( N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). Results In a data-driven approach we found hypoconnectivity in the fronto parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula. Conclusions Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control. PMID- 27250238 TI - Visualization of Steady-State Ionic Concentration Profiles Formed in Electrolytes during Li-Ion Battery Operation and Determination of Mass-Transport Properties by in Situ Magnetic Resonance Imaging. AB - Accurate modeling of Li-ion batteries performance, particularly during the transient conditions experienced in automotive applications, requires knowledge of electrolyte transport properties (ionic conductivity kappa, salt diffusivity D, and lithium ion transference number t(+)) over a wide range of salt concentrations and temperatures. While specific conductivity data can be easily obtained with modern computerized instrumentation, this is not the case for D and t(+). A combination of NMR and MRI techniques was used to solve the problem. The main advantage of such an approach over classical electrochemical methods is its ability to provide spatially resolved details regarding the chemical and dynamic features of charged species in solution, hence the ability to present a more accurate characterization of processes in an electrolyte under operational conditions. We demonstrate herein data on ion transport properties (D and t(+)) of concentrated LiPF6 solutions in a binary ethylene carbonate (EC)-dimethyl carbonate (DMC) 1:1 v/v solvent mixture, obtained by the proposed technique. The buildup of steady-state (time-invariant) ion concentration profiles during galvanostatic experiments with graphite-lithium metal cells containing the electrolyte was monitored by pure phase-encoding single point imaging MRI. We then derived the salt diffusivity and Li(+) transference number over the salt concentration range 0.78-1.27 M from a pseudo-3D combined PFG-NMR and MRI technique. The results obtained with our novel methodology agree with those obtained by electrochemical methods, but in contrast to them, the concentration dependences of salt diffusivity and Li(+) transference number were obtained simultaneously within the single in situ experiment. PMID- 27250236 TI - The CebE/MsiK Transporter is a Doorway to the Cello-oligosaccharide-mediated Induction of Streptomyces scabies Pathogenicity. AB - Streptomyces scabies is an economically important plant pathogen well-known for damaging root and tuber crops by causing scab lesions. Thaxtomin A is the main causative agent responsible for the pathogenicity of S. scabies and cello oligosaccharides are environmental triggers that induce the production of this phytotoxin. How cello-oligosaccharides are sensed or transported in order to induce the virulent behavior of S. scabies? Here we report that the cellobiose and cellotriose binding protein CebE, and MsiK, the ATPase providing energy for carbohydrates transport, are the protagonists of the cello-oligosaccharide mediated induction of thaxtomin production in S. scabies. Our work provides the first example where the transport and not the sensing of major constituents of the plant host is the central mechanism associated with virulence of the pathogen. Our results allow to draw a complete pathway from signal transport to phytotoxin production where each step of the cascade is controlled by CebR, the cellulose utilization regulator. We propose the high affinity of CebE to cellotriose as possible adaptation of S. scabies to colonize expanding plant tissue. Our work further highlights how genes associated with primary metabolism in nonpathogenic Streptomyces species have been recruited as basic elements of virulence in plant pathogenic species. PMID- 27250239 TI - [Knocking on SciELO's doors: a new opportunity for Archivos]. PMID- 27250241 TI - [Evaluation of an intervention for the prevention of musculoskeletal disorders in workers of a pharmaceutical company]. AB - BACKGROUND: The objectives of this study are to: 1) assess the impact of an intervention designed to reduce the prevalence of musculoskeletal discomfort, and 2) analyze whether the impact differs by individual characteristics. METHODS: Quasi-experimental study with pre-post test design and no control group. The study population consisted of 55 workers of a pharmaceutical company. Data were collected through the self-administered Nordic Questionnaire of Musculoskeletal Symptoms, completed before the intervention and again one year later. Differences were examined with the McNemar test. Dependent variables were upper extremity pain, lower extremity pain, back pain and limitation of daily activities due to musculoskeletal disorders. RESULTS: No statistically significant differences were observed. In addition, the prevalence of musculoskeletal discomfort increased in two of the three locations (upper and lower extremities), as well as for related activity limitations, and decreased only in the case of back pain. Differences were also not observed for any of the different stratification variables. CONCLUSIONS: This intervention did not significantly reduce the prevalence of musculoskeletal discomfort, either overall or by specific subgroups. Moreover, except in the case of back pain, prevalence increased. This type of individual interventions should be supplemented by others measures in the workplace. PMID- 27250240 TI - [Non work-related sickness absence in 2013 in a Spanish banking sector company]. AB - OBJECTIVES: To describe the incidence and duration of episodes of non work related temporary sickness absence (SA) between January and December of 2013, by diagnostic groups, in a banking sector company. METHODS: Cross-sectional study of 3.193 episodes of SA (>= day), excluding work-related injuries and illnesses. The distribution of the duration of SA episodes by medical diagnosis was analyzed by calculating the median duration, 25th and 75th percentiles, mean and standard deviation. RESULTS: The median duration of SA was 9 days for cases where there was a medical diagnosis (n=2.931, 91.8%); the 25th and 75th percentiles were 4 and 32 days, respectively. The most frequent pathologies were respiratory (19.9%), followed by musculoskeletal (19.1%) and pregnancy-related disorders (17.3%). Neoplasms had the longest median duration (49 days), followed by pregnancy-related disorders (39 days) and psychiatric disorders (23 days). CONCLUSIONS: Overall sickness absence incidence in our study population was lower, but had a longer duration, as compared to similar studies. The incidence and duration by diagnostic groups were very similar to that reported in the literature, except for pregnancy-related disorders, where both were clearly higher (incidence 4 to 11 times and duration 0.4 times larger) in our company (<0.001). This analysis is useful from a prevention perspective, and suggests the need to prioritize the study to the control of potential workplace exposures that might be affecting pregnant workers' health. PMID- 27250242 TI - [Pulmonary thromboembolism in Occupational Medicine]. AB - Occupational physicians should be familiar with the risk factors and clinical presentation of pulmonary thromboembolism (PTE). PTE belongs to the group ofis a cardiovascular diseases, which are the main cause (40%) of death in Spanish workplaces; at present, they may be considered a work-related injury because of the doctrinal evolution in the legal interpretation of the presumption of iuris tantum. We present the case of a hypertensive and obese adult male who suffered a PTE at his workplace. The availability of a portable pulse oximeter (room air SpO2, 92%) was critical in guiding the decision to refer him urgently to the hospital, where the diagnosis was confirmed. We can conclude that, independently of whether this event is later deemed to be work-related (in this case it was not), occupational physicians must know how to correctly manage and refer affected workers. PMID- 27250243 TI - [Response: Description of dysphonia cases evaluated in a Mutua in 2013]. PMID- 27250244 TI - [Response: Return to work after musculoskeletal disorders: a systematic review of good practices guidelines]. PMID- 27250246 TI - Estimation of the lag time in a subsequent monomer addition model for fibril elongation. AB - Fibrillogenesis, the production or development of protein fibers, has been linked to protein folding diseases. The progress curve of fibrils or aggregates typically takes on a sigmoidal shape with a lag phase, a rapid growth phase, and a final plateau regime. The study of the lag phase and the estimation of its critical timescale provide insight into the factors regulating the fibrillation process. However, methods to estimate a quantitative expression for the lag time rely on empirical expressions, which cannot connect the lag time to kinetic parameters associated with the reaction mechanisms of protein fibrillation. Here we introduce an approach for the estimation of the lag time using the governing rate equations of the elementary reactions of a subsequent monomer addition model for protein fibrillation as a case study. We show that the lag time is given by the sum of the critical timescales for each fibril intermediate in the subsequent monomer addition mechanism and therefore reveals causal connectivity between intermediate species. Furthermore, we find that single-molecule assays of protein fibrillation can exhibit a lag phase without a nucleation process, while dyes and extrinsic fluorescent probe bulk assays of protein fibrillation do not exhibit an observable lag phase during template-dependent elongation. Our approach could be valuable for investigating the effects of intrinsic and extrinsic factors to the protein fibrillation reaction mechanism and provides physicochemical insights into parameters regulating the lag phase. PMID- 27250245 TI - LRP6 acts as a scaffold protein in cardiac gap junction assembly. AB - Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor in the canonical Wnt/beta-catenin signalling. Here, we report the scaffold function of LRP6 in gap junction formation of cardiomyocytes. Cardiac LRP6 is spatially restricted to intercalated discs and binds to gap junction protein connexin 43 (Cx43). A deficiency in LRP6 disrupts Cx43 gap junction formation and thereby impairs the cell-to-cell coupling, which is independent of Wnt/beta-catenin signalling. The defect in Cx43 gap junction resulting from LRP6 reduction is attributable to the defective traffic of de novo Cx43 proteins from the endoplasmic reticulum to the Golgi apparatus, leading to the lysosomal degradation of Cx43 proteins. Accordingly, the hearts of conditional cardiac specific Lrp6-knockout mice consistently exhibit overt reduction of Cx43 gap junction plaques without any abnormality in Wnt signalling and are predisposed to lethal arrhythmias. These findings uncover a distinct role of LRP6 as a platform for intracellular protein trafficking. PMID- 27250247 TI - Towards the development of a screening tool to enhance the detection of elder abuse and neglect by emergency medical technicians (EMTs): a qualitative study. AB - BACKGROUND: To develop a screening tool to enhance elder abuse and neglect detection and reporting rates among emergency medical technicians (EMTs). Our primary aim was to identify the most salient indicators of elder abuse and neglect for potential inclusion on a screening tool. We also sought to identify practical elements of the tool that would optimize EMT uptake and use in the field, such as format, length and number of items, and types of response options available. METHODS: Qualitative data were collected from 23 EMTs and Adult Protective Services (APS) caseworkers that participated in one of five semi structured focus groups. Focus group data were iteratively coded by two coders using inductive thematic identification and data reduction. Findings were subject to interpretation by the research team. RESULTS: EMTs and APS caseworks identified eight domains of items that might be included on a screening tool: (1) exterior home condition; (2) interior living conditions; (3) social support; (4) medical history; (5) caregiving quality; (6) physical condition of the older adult; (7) older adult's behavior; and, (8) EMTs instincts. The screening tool should be based on observable cues in the physical or social environment, be very brief, easily integrated into electronic charting systems, and provide a decision rule for reporting guidance to optimize utility for EMTs in the field. CONCLUSIONS: We described characteristics of a screening tool for EMTs to enhance detection and reporting of elder abuse and neglect to APS. Future research should narrow identified items and evaluate how these domains positively predict confirmed cases of elder abuse and neglect. PMID- 27250248 TI - Labs-on-a-chip meet self-propelled micromotors. AB - This frontier review covers recent advances in the field of nanomaterial-based micromotors for the development of novel labs-on-a-chip (LOCs). In this review, we will discuss how carbon nanomaterials "on-board" of micromotors offer particular promise for diverse LOC applications. New trends in the field, directed towards the use of quantum dots and nanoparticles as functional materials for sophisticated micromotors, will be reviewed. Micromotor strategies using functionalized catalytic microengines to capture and transport (bio)molecules between the different reservoirs of LOC devices will also be covered. These recent advances are bringing closer our hopes for personalized medicine and food safety assurance, among others. PMID- 27250249 TI - National Early Warning Score (NEWS) as an emergency department predictor of disease severity and 90-day survival in the acutely dyspneic patient - a prospective observational study. AB - BACKGROUND: National Early Warning Score (NEWS) was designed to detect deteriorating patients in hospital wards, specifically those at increased risk of ICU admission, cardiac arrest, or death within 24 h. NEWS is not validated for use in Emergency Departments (ED), but emerging data suggest it may be useful. A criticism of NEWS is that patients with chronic poor oxygenation, e.g. severe chronic obstructive pulmonary disease (COPD), will have elevated NEWS also in the absence of acute deterioration, possibly reducing the predictive power of NEWS in this subgroup. We wanted to prospectively evaluate the usefulness of NEWS in unselected adult patients emergently presenting in a Norwegian ED with respiratory distress as main symptom. METHODS: In respiratory distressed patients, NEWS was calculated on ED arrival, after 2-4 h, and the next day. Manchester Triage Scale (MTS) category, age, gender, comorbidity (ASA score), ICU admission, ventilatory support, and discharge diagnoses were noted. Survival status was tracked for >90 days through the Population Registry. Data are medians (25-75th percentiles). Factors predicting 90-day survival were analysed with multiple logistic regression. RESULTS: We included 246 patients; 71 years old (60 80), 89 % home-dwelling, 74 % ASA 3-4, 72 % MTS 1-2, 88 % admitted to hospital. NEWS on arrival was 5 (3-7). NEWS correlated closely with MTS category and maximum in-hospital level of care (ED, ward, high-dependency unit, ICU). Sixteen patients died in-hospital, 26 died after discharge within 90 days. Controlled for age, ASA score, and COPD, a higher NEWS on ED arrival predicted poorer 90-day survival. Increased NEWS also correlated with decreased 30-day- and in-hospital survival and a decreased probability for home-dwelling patients to be discharged directly home. DISCUSSION: In respiratory distressed patients, NEWS on ED arrival correlated closely with triage category and need of ICU admission and predicted long-term out-of-hospital survival controlled for age, comorbidity, and COPD. CONCLUSIONS: NEWS should be explored in the ED setting to determine its role in clinical decision-making and in communication along the acute care chain. PMID- 27250250 TI - Vibrio vulnificus VvhA induces autophagy-related cell death through the lipid raft-dependent c-Src/NOX signaling pathway. AB - VvhA, a virulent factor of Vibrio (V.) vulnificus, induces acute cell death in a destructive manner. Autophagy plays an important role in cell death, but the functional role of VvhA in autophagy-related cell death has not been elucidated yet. We found that rVvhA significantly increased LC3 puncta formation and autophagic flux in promoting the cell death of human intestinal epithelial Caco-2 cells. The cell death induced by rVvhA was independent of lysosomal permeabilizaton and caspase activation. rVvhA induced rapid phosphorylation of c Src in the membrane lipid raft, which resulted in an increased interaction between lipid raft molecule caveolin-1 and NADPH oxidase (NOX) complex Rac1 for ROS production. NOX-mediated ROS signaling induced by rVvhA increased the phosphorylation of extracellular signal-regulated kinase (ERK) and eukaryotic translation initiation factor 2alpha (eIF2alpha) which are required for mRNA expression of Atg5 and Atg16L1 involved in autophagosome formation. In an in vivo model, VvhA increased autophagy activation and paracellular permeabilization in intestinal epithelium. Collectively, the results here show that VvhA plays a pivotal role in the pathogenesis and dissemination of V. vulnificus by autophagy upregulation, through the lipid raft-mediated c-Src/NOX signaling pathway and ERK/eIF2alpha activation. PMID- 27250251 TI - Proteomic Response and Quality Maintenance in Postharvest Fruit of Strawberry (Fragaria * ananassa) to Exogenous Cytokinin. AB - The limitations in current understanding of the molecular mechanisms underlying fruit response to the application of plant growth regulators have increasingly become major challenges in improvement of crop quality. This study aimed to evaluate the response of strawberry to the preharvest application of exogenous cytokinin known as forchlorfenuron (CPPU). Postharvest internal and physiological quality attributes were characterized following storage under different conditions. Hierarchical clustering analysis via a label-free proteomic quantitative approach identified a total of 124 proteins in strawberries across all treatments. The expression profiles of both proteins and genes spanned the ranged role of cytokinin involved in primary and secondary metabolism, stress response, and so on. Eighty-eight proteins and fifty-six proteins were significantly regulated immediately at harvest and after storage, respectively. In general, the glycolysis in strawberry was only regulated by CPPU before storage; in addition to the accelerated photosynthesis and acid metabolism, CPPU application maintained higher capacity of resistance in strawberry to stress stimuli after storage, in comparison to control. Nevertheless, the volatile biosynthesis in strawberry has been suppressed by exogenous CPPU. Novel cytokinin response proteins and processes were identified in addition to the main transcriptomic expression to gain insights into the phytohormone control of fruit postharvest quality. PMID- 27250252 TI - Migrant integration policies and health inequalities in Europe. AB - BACKGROUND: Research on socio-economic determinants of migrant health inequalities has produced a large body of evidence. There is lack of evidence on the influence of structural factors on lives of fragile groups, frequently exposed to health inequalities. The role of poor socio-economic status and country level structural factors, such as migrant integration policies, in explaining migrant health inequalities is unclear. The objective of this paper is to examine the role of migrant socio-economic status and the impact of migrant integration policies on health inequalities during the recent economic crisis in Europe. METHODS: Using the 2012 wave of Eurostat EU-SILC data for a set of 23 European countries, we estimate multilevel mixed-effects ordered logit models for self-assessed poor health (SAH) and self-reported limiting long-standing illnesses (LLS), and multilevel mixed-effects logit models for self-reported chronic illness (SC). We estimate two-level models with individuals nested within countries, allowing for both individual socio-economic determinants of health and country-level characteristics (healthy life years expectancy, proportion of health care expenditure over the GDP, and problems in migrant integration policies, derived from the Migrant Integration Policy Index (MIPEX). RESULTS: Being a non-European citizen or born outside Europe does not increase the odds of reporting poor health conditions, in accordance with the "healthy migrant effect". However, the country context in terms of problems in migrant integration policies influences negatively all of the three measures of health (self-reported health status, limiting long-standing illnesses, and self-reported chronic illness) in foreign people living in European countries, and partially offsets the "healthy migrant effect". CONCLUSIONS: Policies for migrant integration can reduce migrant health disparities. PMID- 27250253 TI - Grassland productivity limited by multiple nutrients. AB - Terrestrial ecosystem productivity is widely accepted to be nutrient limited(1). Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP)(2,3), the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized(4-8). However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+MU), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+MU co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment. PMID- 27250255 TI - PRC2 represses dedifferentiation of mature somatic cells in Arabidopsis. AB - Plant somatic cells are generally acknowledged to retain totipotency, the potential to develop into any cell type within an organism. This astonishing plasticity may contribute to a high regenerative capacity on severe damage, but how plants control this potential during normal post-embryonic development remains largely unknown(1,2). Here we show that POLYCOMB REPRESSIVE COMPLEX 2 (PRC2), a chromatin regulator that maintains gene repression through histone modification, prevents dedifferentiation of mature somatic cells in Arabidopsis thaliana roots. Loss-of-function mutants in PRC2 subunits initially develop unicellular root hairs indistinguishable from those in wild type but fail to retain the differentiated state, ultimately resulting in the generation of an unorganized cell mass and somatic embryos from a single root hair. Strikingly, mutant root hairs complete the normal endoreduplication programme, increasing their nuclear ploidy, but subsequently reinitiate mitotic division coupled with successive DNA replication. Our data show that the WOUND INDUCED DEDIFFERENTIATION3 (WIND3) and LEAFY COTYLEDON2 (LEC2) genes are among the PRC2 targets involved in this reprogramming, as their ectopic overexpression partly phenocopies the dedifferentiation phenotype of PRC2 mutants. These findings unveil the pivotal role of PRC2-mediated gene repression in preventing unscheduled reprogramming of fully differentiated plant cells. PMID- 27250256 TI - Systematic analysis of how phytochrome B dimerization determines its specificity. AB - Phytochromes are red/far-red-light detecting photoreceptors that regulate plant growth and development. They photo-interconvert between an inactive Pr (red-light absorbing) and a physiologically active Pfr (far-red-light absorbing) form, acting as light-controlled molecular switches. Although the two major plant phytochromes A (phyA) and B (phyB) share similar absorption properties, they exhibit dramatic differences in their action spectra. Since both phytochromes antagonistically regulate seedling development under vegetative shade, it is essential for plants to clearly distinguish between phyA and phyB action. This discrimination is not comprehensible solely by the molecular properties of the phytochromes, but is evidently due to the dynamics of the phytochrome system. Using an integrated experimental and mathematical modelling approach we show that phytochrome dimerization is an essential element for phyB function. Our findings reveal that light-independent Pfr to Pr relaxation (dark reversion) and association/dissociation to nuclear bodies (NBs) severely depend on the conformational state of the phyB dimer. We conclude that only Pfr-Pfr homodimers of phyB can be responsible for triggering physiological responses, leading to a suppression of phyB function in the far-red range of the light spectrum. PMID- 27250257 TI - Heterosis and inbreeding depression of epigenetic Arabidopsis hybrids. AB - We have addressed the possible epigenetic contribution to heterosis using epigenetic inbred lines (epiRILs) with varying levels and distributions of DNA methylation. One line consistently displayed parent-of-origin heterosis for growth-related traits. Genome-wide transcription profiling followed by a candidate gene approach revealed 33 genes with altered regulation in crosses of this line that could contribute to the observed heterosis. Although none of the candidate genes could explain hybrid vigour, we detected intriguing, hybrid specific transcriptional regulation of the RPP5 gene, encoding a growth suppressor. RPP5 displayed intermediate transcript levels in heterotic hybrids; surprisingly however, with global loss of fitness of their F2 progeny, we observed striking under-representation of the hybrid-like intermediate levels. Thus, in addition to genetic factors contributing to heterosis, our results strongly suggest that epigenetic diversity and epigenetic regulation of transcription play a role in hybrid vigour and inbreeding depression, and also in the absence of parental genetic diversity. PMID- 27250259 TI - Hypoxia and development: Air conditional. PMID- 27250258 TI - V-ATPase activity in the TGN/EE is required for exocytosis and recycling in Arabidopsis. AB - In plants, vacuolar H(+)-ATPase (V-ATPase) activity acidifies both the trans Golgi network/early endosome (TGN/EE) and the vacuole. This dual V-ATPase function has impeded our understanding of how the pH homeostasis within the plant TGN/EE controls exo- and endocytosis. Here, we show that the weak V-ATPase mutant deetiolated3 (det3) displayed a pH increase in the TGN/EE, but not in the vacuole, strongly impairing secretion and recycling of the brassinosteroid receptor and the cellulose synthase complexes to the plasma membrane, in contrast to mutants lacking tonoplast-localized V-ATPase activity only. The brassinosteroid insensitivity and the cellulose deficiency defects in det3 were tightly correlated with reduced Golgi and TGN/EE motility. Thus, our results provide strong evidence that acidification of the TGN/EE, but not of the vacuole, is indispensable for functional secretion and recycling in plants. PMID- 27250260 TI - Nitrogen-use efficiency: Transport solution in rice variations. PMID- 27250262 TI - Grassland ecology: Complexity of nutrient constraints. PMID- 27250261 TI - Auxin: Shape matters. PMID- 27250263 TI - Encouraging metadata curation in the Diversity Seek initiative. PMID- 27250264 TI - Development: Acting your cellular age. PMID- 27250265 TI - Soil fertility decline at the base of rural poverty in sub-Saharan Africa. PMID- 27250266 TI - Hybrid vigour: Infertility rescue. PMID- 27250268 TI - Genome evolution: From big to immense. PMID- 27250267 TI - Thermotolerance: Waste management. PMID- 27250269 TI - Ecology: Sourcing water in a savannah. PMID- 27250270 TI - Jurassic bark. PMID- 27250271 TI - Perspective: The first ten years of broadband chirped pulse Fourier transform microwave spectroscopy. AB - Since its invention in 2006, the broadband chirped pulse Fourier transform spectrometer has transformed the field of microwave spectroscopy. The technique enables the collection of a >=10 GHz bandwidth spectrum in a single shot of the spectrometer, which allows broadband, high-resolution microwave spectra to be acquired several orders of magnitude faster than what was previously possible. We discuss the advantages and challenges associated with the technique and look back on the first ten years of chirped pulse Fourier transform spectroscopy. In addition to enabling faster-than-ever structure determination of increasingly complex species, the technique has given rise to an assortment of entirely new classes of experiments, ranging from chiral sensing by three-wave mixing to microwave detection of multichannel reaction kinetics. However, this is only the beginning. Future generations of microwave experiments will make increasingly creative use of frequency-agile pulse sequences for the coherent manipulation and interrogation of molecular dynamics. PMID- 27250272 TI - Communication: Quantum six-dimensional calculations of the coupled translation rotation eigenstates of H2O@C60. AB - We report rigorous quantum calculations of the translation-rotation (TR) eigenstates of para- and ortho-H2O@C60. They provide a comprehensive description of the dynamical behavior of H2O inside the fullerene having icosahedral (Ih) symmetry. The TR eigenstates are assigned in terms of the irreducible representations of the proper symmetry group of H2O@C60, as well as the appropriate translational and rotational quantum numbers. The coupling between the orbital and the rotational angular momenta of the caged H2O gives rise to the total angular momentum lambda, which additionally labels each TR level. The calculated TR levels allow tentative assignments of a number of transitions in the recent experimental INS spectra of H2O@C60 that have not been assigned previously. PMID- 27250273 TI - Diffusive flux in a model of stochastically gated oxygen transport in insect respiration. AB - Oxygen delivery to insect tissues is controlled by transport through a branched tubular network that is connected to the atmosphere by valve-like gates, known as spiracles. In certain physiological regimes, the spiracles appear to be randomly switching between open and closed states. Quantitative analysis of this regime leads a reaction-diffusion problem with stochastically switching boundary condition. We derive an expression for the diffusive flux at long times in this problem. Our approach starts with the derivation of the passage probability for a single particle that diffuses between a stochastically gated boundary, which models the opening and closing spiracle, and the perfectly absorbing boundary, which models oxygen absorption by the tissue. This passage probability is then used to derive an expression giving the diffusive flux as a function of the geometric parameters of the tube and characteristic time scales of diffusion and gate dynamics. PMID- 27250274 TI - The explicitly correlated same number of optimized parameters (SNOOP-F12) scheme for calculating intermolecular interaction energies. AB - We augment the recently introduced same number of optimized parameters (SNOOP) scheme [K. Kristensen et al., J. Chem. Phys. 142, 114116 (2015)] for calculating interaction energies of molecular dimers with an F12 correction and generalize the method to enable the determination of interaction energies of general molecular clusters. The SNOOP, uncorrected (UC), and counterpoise (CP) schemes with/without an F12 correction are compared for the S22 test set of Jurecka et al. [Phys. Chem. Chem. Phys. 8, 1985 (2006)]-which consists of 22 molecular dimers of biological importance-and for water and methane molecular clusters. The calculations have been performed using the Resolution of the Identity second order Moller-Plesset perturbation theory method. We conclude from the results that the SNOOP scheme generally yields interaction energies closer to the complete basis set limit value than the UC and CP approaches, regardless of whether the F12 correction is applied or not. Specifically, using the SNOOP scheme with an F12 correction yields the computationally most efficient way of achieving accurate results at low basis set levels. These conclusions hold both for molecular dimers and more general molecular clusters. PMID- 27250275 TI - First time combination of frozen density embedding theory with the algebraic diagrammatic construction scheme for the polarization propagator of second order. AB - The combination of Frozen Density Embedding Theory (FDET) and the Algebraic Diagrammatic Construction (ADC) scheme for the polarization propagator for describing environmental effects on electronically excited states is presented. Two different ways of interfacing and expressing the so-called embedding operator are introduced. The resulting excited states are compared with supermolecular calculations of the total system at the ADC(2) level of theory. Molecular test systems were chosen to investigate molecule-environment interactions of varying strength from dispersion interaction up to multiple hydrogen bonds. The overall difference between the supermolecular and the FDE-ADC calculations in excitation energies is lower than 0.09 eV (max) and 0.032 eV in average, which is well below the intrinsic error of the ADC(2) method itself. PMID- 27250276 TI - Computing bulk and shear viscosities from simulations of fluids with dissipative and stochastic interactions. AB - Exact values for bulk and shear viscosity are important to characterize a fluid, and they are a necessary input for a continuum description. Here we present two novel methods to compute bulk viscosities by non-equilibrium molecular dynamics simulations of steady-state systems with periodic boundary conditions - one based on frequent particle displacements and one based on the application of external bulk forces with an inhomogeneous force profile. In equilibrium simulations, viscosities can be determined from the stress tensor fluctuations via Green-Kubo relations; however, the correct incorporation of random and dissipative forces is not obvious. We discuss different expressions proposed in the literature and test them at the example of a dissipative particle dynamics fluid. PMID- 27250277 TI - Sequential double excitations from linear-response time-dependent density functional theory. AB - Traditional UV/vis and X-ray spectroscopies focus mainly on the study of excitations starting exclusively from electronic ground states. However there are many experiments where transitions from excited states, both absorption and emission, are probed. In this work we develop a formalism based on linear response time-dependent density functional theory to investigate spectroscopic properties of excited states. We apply our model to study the excited-state absorption of a diplatinum(II) complex under X-rays, and transient vis/UV absorption of pyrene and azobenzene. PMID- 27250278 TI - A variational master equation approach to quantum dynamics with off-diagonal coupling in a sub-Ohmic environment. AB - A master equation approach based on an optimized polaron transformation is adopted for dynamics simulation with simultaneous diagonal and off-diagonal spin boson coupling. Two types of bath spectral density functions are considered, the Ohmic and the sub-Ohmic. The off-diagonal coupling leads asymptotically to a thermal equilibrium with a nonzero population difference Pz(t -> infinity) ? 0, which implies localization of the system, and it also plays a role in restraining coherent dynamics for the sub-Ohmic case. Since the new method can extend to the stronger coupling regime, we can investigate the coherent-incoherent transition in the sub-Ohmic environment. Relevant phase diagrams are obtained for different temperatures. It is found that the sub-Ohmic environment allows coherent dynamics at a higher temperature than the Ohmic environment. PMID- 27250279 TI - Modified Newton-Raphson GRAPE methods for optimal control of spin systems. AB - Quadratic convergence throughout the active space is achieved for the gradient ascent pulse engineering (GRAPE) family of quantum optimal control algorithms. We demonstrate in this communication that the Hessian of the GRAPE fidelity functional is unusually cheap, having the same asymptotic complexity scaling as the functional itself. This leads to the possibility of using very efficient numerical optimization techniques. In particular, the Newton-Raphson method with a rational function optimization (RFO) regularized Hessian is shown in this work to require fewer system trajectory evaluations than any other algorithm in the GRAPE family. This communication describes algebraic and numerical implementation aspects (matrix exponential recycling, Hessian regularization, etc.) for the RFO Newton-Raphson version of GRAPE and reports benchmarks for common spin state control problems in magnetic resonance spectroscopy. PMID- 27250280 TI - Molecular electric moments calculated by using natural orbital functional theory. AB - The molecular electric dipole, quadrupole, and octupole moments of a selected set of 21 spin-compensated molecules are determined employing the extended version of the Piris natural orbital functional 6 (PNOF6), using the triple-zeta Gaussian basis set with polarization functions developed by Sadlej, at the experimental geometries. The performance of the PNOF6 is established by carrying out a statistical analysis of the mean absolute errors with respect to the experiment. The calculated PNOF6 electric moments agree satisfactorily with the corresponding experimental data and are in good agreement with the values obtained by accurate ab initio methods, namely, the coupled-cluster single and doubles and multi reference single and double excitation configuration interaction methods. PMID- 27250281 TI - Analytical correlation functions for motion through diffusivity landscapes. AB - Diffusion of a particle through an energy and diffusivity landscape is a very general phenomenon in numerous systems of soft and condensed matter. On the one hand, theoretical frameworks such as Langevin and Fokker-Planck equations present valuable accounts to understand these motions in great detail, and numerous studies have exploited these approaches. On the other hand, analytical solutions for correlation functions, as, e.g., desired by experimentalists for data fitting, are only available for special cases. We explore the possibility to use different theoretical methods in the specific picture of time-dependent switching between diffusive states to derive analytical functions that allow to link experimental and simulation results to theoretical calculations. In particular, we present a closed formula for diffusion switching between two states, as well as a general recipe of how to generalize the formula to multiple states. PMID- 27250282 TI - Kinetic-energy matrix elements for atomic Hylleraas-CI wave functions. AB - Hylleraas-CI is a superposition-of-configurations method in which each configuration is constructed from a Slater-type orbital (STO) product to which is appended (linearly) at most one interelectron distance rij. Computations of the kinetic energy for atoms by this method have been difficult due to the lack of formulas expressing these matrix elements for general angular momentum in terms of overlap and potential-energy integrals. It is shown here that a strategic application of angular-momentum theory, including the use of vector spherical harmonics, enables the reduction of all atomic kinetic-energy integrals to overlap and potential-energy matrix elements. The new formulas are validated by showing that they yield correct results for a large number of integrals published by other investigators. PMID- 27250283 TI - An integral-factorized implementation of the driven similarity renormalization group second-order multireference perturbation theory. AB - We report an efficient implementation of a second-order multireference perturbation theory based on the driven similarity renormalization group (DSRG MRPT2) [C. Li and F. A. Evangelista, J. Chem. Theory Comput. 11, 2097 (2015)]. Our implementation employs factorized two-electron integrals to avoid storage of large four-index intermediates. It also exploits the block structure of the reference density matrices to reduce the computational cost to that of second order Moller-Plesset perturbation theory. Our new DSRG-MRPT2 implementation is benchmarked on ten naphthyne isomers using basis sets up to quintuple-zeta quality. We find that the singlet-triplet splittings (DeltaST) of the naphthyne isomers strongly depend on the equilibrium structures. For a consistent set of geometries, the DeltaST values predicted by the DSRG-MRPT2 are in good agreements with those computed by the reduced multireference coupled cluster theory with singles, doubles, and perturbative triples. PMID- 27250284 TI - Explicitly correlated second-order Moller-Plesset perturbation theory in a Divide Expand-Consolidate (DEC) context. AB - We present the DEC-RIMP2-F12 method where we have augmented the Divide Expand Consolidate resolution-of-the-identity second-order Moller-Plesset perturbation theory method (DEC-RIMP2) [P. Baudin et al., J. Chem. Phys. 144, 054102 (2016)] with an explicitly correlated (F12) correction. The new method is linear-scaling, massively parallel, and it corrects for the basis set incompleteness error in an efficient manner. In addition, we observe that the F12 contribution decreases the domain error of the DEC-RIMP2 correlation energy by roughly an order of magnitude. An important feature of the DEC scheme is the inherent error control defined by a single parameter, and this feature is also retained for the DEC RIMP2-F12 method. In this paper we present the working equations for the DEC RIMP2-F12 method and proof of concept numerical results for a set of test molecules. PMID- 27250285 TI - A projected approximation to strongly contracted N-electron valence perturbation theory for DMRG wavefunctions. AB - A novel approach to strongly contracted N-electron valence perturbation theory (SC-NEVPT2) as a means of describing dynamic electron correlation for quantum chemical density matrix renormalization group (DMRG) calculations is presented. In this approach the strongly contracted perturber functions are projected onto a renormalized Hilbert space. Compared to a straightforward implementation of SC NEVPT2 with DMRG wavefunctions, the computational scaling and storage requirements are reduced. This favorable scaling opens up the possibility of calculations with larger active spaces. A specially designed renormalization scheme ensures that both the electronic ground state and the perturber functions are well represented in the renormalized Hilbert space. Test calculations on the N2 and [Cu2O2(en)2](2+) demonstrate some key properties of the method and indicate its capabilities. PMID- 27250286 TI - On the errors of local density (LDA) and generalized gradient (GGA) approximations to the Kohn-Sham potential and orbital energies. AB - In spite of the high quality of exchange-correlation energies Exc obtained with the generalized gradient approximations (GGAs) of density functional theory, their xc potentials vxc are strongly deficient, yielding upshifts of ca. 5 eV in the orbital energy spectrum (in the order of 50% of high-lying valence orbital energies). The GGAs share this deficiency with the local density approximation (LDA). We argue that this error is not caused by the incorrect long-range asymptotics of vxc or by self-interaction error. It arises from incorrect density dependencies of LDA and GGA exchange functionals leading to incorrect (too repulsive) functional derivatives (i.e., response parts of the potentials). The vxc potential is partitioned into the potential of the xc hole vxchole (twice the xc energy density epsilonxc), which determines Exc, and the response potential vresp, which does not contribute to Exc explicitly. The substantial upshift of LDA/GGA orbital energies is due to a too repulsive LDA exchange response potential vxresp (LDA) in the bulk region. Retaining the LDA exchange hole potential plus the B88 gradient correction to it but replacing the response parts of these potentials by the model orbital-dependent response potential vxresp (GLLB) of Gritsenko et al. [Phys. Rev. A 51, 1944 (1995)], which has the proper step-wise form, improves the orbital energies by more than an order of magnitude. Examples are given for the prototype molecules: dihydrogen, dinitrogen, carbon monoxide, ethylene, formaldehyde, and formic acid. PMID- 27250287 TI - Character of intermolecular interaction in pyridine-argon complex: Ab initio potential energy surface, internal dynamics, and interrelations between SAPT energy components. AB - The pyridine-Ar (PAr) van der Waals (vdW) complex is studied using a high level ab initio method. Its structure, binding energy, and intermolecular vibrational states are determined from the analytical potential energy surface constructed from interaction energy (IE) values computed at the coupled cluster level of theory with single, double, and perturbatively included triple excitations with the augmented correlation consistent polarized valence double-zeta (aug-cc-pVDZ) basis set complemented by midbond functions. The structure of the complex at its global minimum with Ar at a distance of 3.509 A from the pyridine plane and shifted by 0.218 A from the center of mass towards nitrogen agrees well with the corresponding equilibrium structure derived previously from the rotational spectrum of PAr. The PAr binding energy De of 392 cm(-1) is close to that of 387 cm(-1) calculated earlier at the same ab initio level for the prototypical benzene-Ar (BAr) complex. However, under an extension of the basis set, De for PAr becomes slightly lower than De for BAr. The ab initio vdW vibrational energy levels allow us to estimate the reliability of the methods for the determination of the vdW fundamentals from the rotational spectra. To disclose the character of the intermolecular interaction in PAr, the symmetry-adapted perturbation theory (SAPT) is employed for the analysis of different physical contributions to IE. It is found that SAPT components of IE can be approximately expressed in the binding region by only two of them: the exchange repulsion and dispersion energy. The total induction effect is negligible. The interrelations between various SAPT components found for PAr are fulfilled for a few other complexes involving aromatic molecules and Ar or Ne, which indicates that they are valid for all rare gas (Rg) atoms and aromatics. PMID- 27250288 TI - Intermediate vibrational coordinate localization with harmonic coupling constraints. AB - Optimized normal coordinates can significantly improve the speed and accuracy of vibrational frequency calculations. However, over-localization can occur when using unconstrained spatial localization techniques. The unintuitive mixtures of stretching and bending coordinates that result can make interpreting spectra more difficult and also cause artificial increases in mode-coupling during anharmonic calculations. Combining spatial localization with a constraint on the coupling between modes can be used to generate coordinates with properties in-between the normal and fully localized schemes. These modes preserve the diagonal nature of the mass-weighted Hessian matrix to within a specified tolerance and are found to prevent contamination between the stretching and bending vibrations of the molecules studied without a priori classification of the different types of vibration present. Relaxing the constraint can also be used to identify which normal modes form specific groups of localized modes. The new coordinates are found to center on more spatially delocalized functional groups than their fully localized counterparts and can be used to tune the degree of vibrational correlation energy during anharmonic calculations. PMID- 27250289 TI - Natural ionization orbitals for interpreting electron detachment processes. AB - A compact orbital representation of ionization processes is described utilizing the difference of calculated one-particle density matrices. Natural orbital analysis involving this difference density matrix simplifies interpretation of electronic detachment processes and allows differentiation between one-electron transitions and shake-up/shake-off transitions, in which one-electron processes are accompanied by excitation of a second electron into the virtual orbital space. PMID- 27250290 TI - G4CEP: A G4 theory modification by including pseudopotential for molecules containing first-, second- and third-row representative elements. AB - The G4CEP composite method was developed from the respective G4 all-electron version by considering the implementation of compact effective pseudopotential (CEP). The G3/05 test set was used as reference to benchmark the adaptation by treating in this work atoms and compounds from the first and second periods of the periodic table, as well as representative elements of the third period, comprising 440 thermochemical data. G4CEP has not reached a so high level of accuracy as the G4 all-electron theory. G4CEP presented a mean absolute error around 1.09 kcal mol(-1), while the original method presents a deviation corresponding to 0.83 kcal mol(-1). The similarity of the optimized molecular geometries between G4 and G4CEP indicates that the core-electron effects and basis set adjustments may be pointed out as a significant factor responsible for the large discrepancies between the pseudopotential results and the experimental data, or even that the all-electron calculations are more efficient either in its formulation or in the cancellation of errors. When the G4CEP mean absolute error (1.09 kcal mol(-1)) is compared to 1.29 kcal mol(-1) from G3CEP, it does not seem so efficient. However, while the G3CEP uncertainty is +/-4.06 kcal mol(-1), the G4CEP deviation is +/-2.72 kcal mol(-1). Therefore, the G4CEP theory is considerably more reliable than any previous combination of composite theory and pseudopotential, particularly for enthalpies of formation and electron affinities. PMID- 27250291 TI - S-matrix decomposition, natural reaction channels, and the quantum transition state approach to reactive scattering. AB - A new approach for the quantum-state resolved analysis of polyatomic reactions is introduced. Based on the singular value decomposition of the S-matrix, energy dependent natural reaction channels and natural reaction probabilities are defined. It is shown that the natural reaction probabilities are equal to the eigenvalues of the reaction probability operator [U. Manthe and W. H. Miller, J. Chem. Phys. 99, 3411 (1993)]. Consequently, the natural reaction channels can be interpreted as uniquely defined pathways through the transition state of the reaction. The analysis can efficiently be combined with reactive scattering calculations based on the propagation of thermal flux eigenstates. In contrast to a decomposition based straightforwardly on thermal flux eigenstates, it does not depend on the choice of the dividing surface separating reactants from products. The new approach is illustrated studying a prototypical example, the H + CH4 -> H2 + CH3 reaction. The natural reaction probabilities and the contributions of the different vibrational states of the methyl product to the natural reaction channels are calculated and discussed. The relation between the thermal flux eigenstates and the natural reaction channels is studied in detail. PMID- 27250292 TI - Rungs 1 to 4 of DFT Jacob's ladder: Extensive test on the lattice constant, bulk modulus, and cohesive energy of solids. AB - A large panel of old and recently proposed exchange-correlation functionals belonging to rungs 1 to 4 of Jacob's ladder of density functional theory are tested (with and without a dispersion correction term) for the calculation of the lattice constant, bulk modulus, and cohesive energy of solids. Particular attention will be paid to the functionals MGGA_MS2 [J. Sun et al., J. Chem. Phys. 138, 044113 (2013)], mBEEF [J. Wellendorff et al., J. Chem. Phys. 140, 144107 (2014)], and SCAN [J. Sun et al., Phys. Rev. Lett. 115, 036402 (2015)] which are meta-generalized gradient approximations (meta-GGA) and are developed with the goal to be universally good. Another goal is also to determine for which semilocal functionals and groups of solids it is beneficial (or not necessary) to use the Hartree-Fock exchange or a dispersion correction term. It is concluded that for strongly bound solids, functionals of the GGA, i.e., rung 2 of Jacob's ladder, are as accurate as the more sophisticated functionals of the higher rungs, while it is necessary to use dispersion corrected functionals in order to expect at least meaningful results for weakly bound solids. If results for finite systems are also considered, then the meta-GGA functionals are overall clearly superior to the GGA functionals. PMID- 27250293 TI - Analytic ab initio-based molecular interaction potential for the BrO?H2O complex. AB - Radical halogen oxide species play important roles within atmospheric processes, specifically those responsible for the removal of O3. To facilitate future investigations on this family of compounds, RCCSD(T)/aug-cc-pVQZ-level electronic structure calculations were employed to generate individual-molecule optimized geometries, as well as to determine the global minimum energy structure for the BrO?H2O complex. This information facilitated the generation of several one dimensional potential energy surface (PES) scans for the BrO?H2O complex. Scans were performed for both the ground state and the first excited state; this inclusion is due to a low-lying first electronic excited-state energy. These rigid-geometry PES scans were used both to generate a novel analytic interaction potential by modifying the existing Thole-type model used for water and to the fitted potential function. This interaction potential features anisotropic atomic polarizabilities facilitating appropriate modeling of the physics regarding the unpaired electron residing within the p-orbitals of the oxygen atom of the bromine oxide radical. The intention of this work is to facilitate future molecular dynamics simulations involving the interaction between the BrO radical and water clusters as a first step in devising possible novel chemistries taking place at the water interface of clouds within the atmosphere. PMID- 27250294 TI - Ab initio electronic structure of quasi-two-dimensional materials: A "native" Gaussian-plane wave approach. AB - Ab initio electronic structure calculations of two-dimensional layered structures are typically performed using codes that were developed for three-dimensional structures, which are periodic in all three directions. The introduction of a periodicity in the third direction (perpendicular to the layer) is completely artificial and may lead in some cases to spurious results and to difficulties in treating the action of external fields. In this paper we develop a new approach, which is "native" to quasi-2D materials, making use of basis function that are periodic in the plane, but atomic-like in the perpendicular direction. We show how some of the basic tools of ab initio electronic structure theory - density functional theory, GW approximation and Bethe-Salpeter equation - are implemented in the new basis. We argue that the new approach will be preferable to the conventional one in treating the peculiarities of layered materials, including the long range of the unscreened Coulomb interaction in insulators, and the effects of strain, corrugations, and external fields. PMID- 27250295 TI - Adaptive vibrational configuration interaction (A-VCI): A posteriori error estimation to efficiently compute anharmonic IR spectra. AB - A new variational algorithm called adaptive vibrational configuration interaction (A-VCI) intended for the resolution of the vibrational Schrodinger equation was developed. The main advantage of this approach is to efficiently reduce the dimension of the active space generated into the configuration interaction (CI) process. Here, we assume that the Hamiltonian writes as a sum of products of operators. This adaptive algorithm was developed with the use of three correlated conditions, i.e., a suitable starting space, a criterion for convergence, and a procedure to expand the approximate space. The velocity of the algorithm was increased with the use of a posteriori error estimator (residue) to select the most relevant direction to increase the space. Two examples have been selected for benchmark. In the case of H2CO, we mainly study the performance of A-VCI algorithm: comparison with the variation-perturbation method, choice of the initial space, and residual contributions. For CH3CN, we compare the A-VCI results with a computed reference spectrum using the same potential energy surface and for an active space reduced by about 90%. PMID- 27250296 TI - Bottom-up coarse-grained models with predictive accuracy and transferability for both structural and thermodynamic properties of heptane-toluene mixtures. AB - This work investigates the promise of a "bottom-up" extended ensemble framework for developing coarse-grained (CG) models that provide predictive accuracy and transferability for describing both structural and thermodynamic properties. We employ a force-matching variational principle to determine system-independent, i.e., transferable, interaction potentials that optimally model the interactions in five distinct heptane-toluene mixtures. Similarly, we employ a self-consistent pressure-matching approach to determine a system-specific pressure correction for each mixture. The resulting CG potentials accurately reproduce the site-site rdfs, the volume fluctuations, and the pressure equations of state that are determined by all-atom (AA) models for the five mixtures. Furthermore, we demonstrate that these CG potentials provide similar accuracy for additional heptane-toluene mixtures that were not included their parameterization. Surprisingly, the extended ensemble approach improves not only the transferability but also the accuracy of the calculated potentials. Additionally, we observe that the required pressure corrections strongly correlate with the intermolecular cohesion of the system-specific CG potentials. Moreover, this cohesion correlates with the relative "structure" within the corresponding mapped AA ensemble. Finally, the appendix demonstrates that the self-consistent pressure matching approach corresponds to minimizing an appropriate relative entropy. PMID- 27250297 TI - Accuracy and computational efficiency of real-time subspace propagation schemes for the time-dependent density functional theory. AB - Time-dependent Density Functional Theory (TDDFT) has become successful for its balance of economy and accuracy. However, the application of TDDFT to large systems or long time scales remains computationally prohibitively expensive. In this paper, we investigate the numerical stability and accuracy of two subspace propagation methods to solve the time-dependent Kohn-Sham equations with finite and periodic boundary conditions. The bases considered are the Lanczos basis and the adiabatic eigenbasis. The results are compared to a benchmark fourth-order Taylor expansion of the time propagator. Our results show that it is possible to use larger time steps with the subspace methods, leading to computational speedups by a factor of 2-3 over Taylor propagation. Accuracy is found to be maintained for certain energy regimes and small time scales. PMID- 27250298 TI - Ion aggregation in high salt solutions. V. Graph entropy analyses of ion aggregate structure and water hydrogen bonding network. AB - Dissolved ions in water tend to form polydisperse ion aggregates such as ion pairs, relatively compact ion clusters, and even spatially extended ion networks with increasing salt concentration. Combining molecular dynamics simulation and graph theoretical analysis methods, we recently studied morphological structures of ion aggregates with distinctively different characteristics. They can be distinguished from each other by calculating various spectral graph theoretical properties such as eigenvalues and eigenvectors of adjacency matrices of ion aggregates and water hydrogen-bonding networks, minimum path lengths, clustering coefficients, and degree distributions. Here, we focus on percolation and graph entropic properties of ion aggregates and water hydrogen-bonding networks in high salt solutions. Ion network-forming K(+) and SCN(-) ions at high concentrations show a percolating behavior in their aqueous solutions, but ion cluster-forming ions in NaCl solutions do not show such a transition from isolated ion aggregates to percolating ion-water mixture morphology. Despite that the ion aggregate structures are strikingly different for either cluster- or network-forming ions in high salt solutions, it is interesting that the water structures remain insensitive to the electrostatic properties, such as charge densities and polydentate properties, of dissolved ions, and morphological structures of water H-bonding networks appear to be highly robust regardless of the nature and concentration of salt. We anticipate that the present graph entropy analysis results would be of use in understanding a variety of anomalous behaviors of interfacial water around biomolecules as well as electric conductivities of high electrolyte solutions. PMID- 27250299 TI - T2-Filtered T2 - T2 Exchange NMR. AB - This work introduces an alternative way to perform the T2 - T2 Exchange NMR experiment. Rather than varying the number of pi pulses in the first CPMG cycle of the T2 - T2 Exchange NMR pulse sequence, as used to obtain the 2D correlation maps, it is fixed and small enough to act as a short T2-filter. By varying the storage time, a set of 1D measurements of T2 distributions can be obtained to reveal the effects of the migration dynamics combined with relaxation effects. This significantly reduces the required time to perform the experiment, allowing a more in-depth study of exchange dynamics and relaxation processes with improved signal-to-noise ratio. These aspects stand as basis of this novel experiment, T2 Filtered T2 - T2 Exchange NMR or simply T2 F-TREx. PMID- 27250300 TI - Lieb-Liniger-like model of quantum solvation in CO-(4)HeN clusters. AB - Small (4)He clusters doped with various molecules allow for the study of "quantum solvation" as a function of cluster size. A peculiarity of quantum solvation is that, as the number of (4)He atoms is increased from N = 1, the solvent appears to decouple from the molecule which, in turn, appears to undergo free rotation. This is generally taken to signify the onset of "microscopic superfluidity." Currently, little is known about the quantum mechanics of the decoupling mechanism, mainly because the system is a quantum (N + 1)-body problem in three dimensions which makes computations difficult. Here, a one-dimensional model is studied in which the (4)He atoms are confined to revolve on a ring and encircle a rotating CO molecule. The Lanczos algorithm is used to investigate the eigenvalue spectrum as the number of (4)He atoms is varied. Substantial solvent decoupling is observed for as few as N = 5 (4)He atoms. Examination of the Hamiltonian matrix, which has an almost block diagonal structure, reveals increasingly weak inter-block (solvent-molecule) coupling as the number of (4)He atoms is increased. In the absence of a dopant molecule the system is similar to a Lieb Liniger (LL) gas and we find a relatively rapid transition to the LL limit as N is increased. In essence, the molecule initially-for very small N-provides a central, if relatively weak, attraction to organize the cluster; as more (4)He atoms are added, the repulsive interactions between the identical bosons start to dominate as the solvation ring (shell) becomes more crowded which causes the molecule to start to decouple. For low N, the molecule pins the atoms in place relative to itself; as N increases the atom-atom repulsion starts to dominate the Hamiltonian and the molecule decouples. We conclude that, while the notion of superfluidity is a useful and correct description of the decoupling process, a molecular viewpoint provides complementary insights into the quantum mechanism of the transition from a molecular cluster to a quantum solvated molecule. PMID- 27250301 TI - Full-dimensional vibrational calculations of five-atom molecules using a combination of Radau and Jacobi coordinates: Applications to methane and fluoromethane. AB - Full quantum mechanical calculations of vibrational energies of methane and fluoromethane are carried out using a polyspherical description combining Radau and Jacobi coordinates. The Hamiltonian is built in a potential-optimized discrete variable representation, and vibrational energies are solved using an iterative eigensolver. This new approach can be applied to a large variety of molecules. In particular, we show that it is able to accurately and efficiently compute eigenstates for four different molecules : CH4, CHD3, CH2D2, and CH3F. Very good agreement is obtained with the results reported previously in the literature with different approaches and with experimental data. PMID- 27250302 TI - Ab initio studies of the Rg-NO(+)(X(1)Sigma(+)) van der Waals complexes (Rg = He, Ne, Ar, Kr, and Xe). AB - We used the explicitly correlated variant of the coupled clusters method with single, double, and noniterative triple excitations [CCSD(T)-F12] to compute two dimensional potential energy surfaces of van der Waals complexes formed by rare gas atoms (Rg) and NO(+)(X(1)Sigma(+)) cations. We used the correlation consistent, triple-zeta (cc-pVTZ-F12) atomic basis sets, and for Kr and Xe rare gases, we employed corresponding pseudopotential cc-pVTZ-PP-F12 atomic basis sets. These basis sets were additionally augmented with mid-bond functions. The complexes are all of skewed T-shape type with Rg atom being closer to the N-side. Using analytical representation of the potentials, we have estimated zero-point energy corrected dissociation energies from anharmonic calculations with BOUND program and also from the harmonic approximation. The binding energies increase with the polarization of the Rg atom in series from He to Xe and are 196 cm(-1), 360 cm(-1), 1024 cm(-1), 1434 cm(-1), and 2141 cm(-1), respectively. Their corresponding dissociation energies are 132 cm(-1), 300 cm(-1), 927 cm(-1), 1320 cm(-1), and 1994 cm(-1) for the complexes with He to Xe, respectively. We find good agreement with previous theoretical and experimental results. The harmonic vibrational frequencies were calculated for the bending and stretching modes of the Rg-NO(+) complexes. PMID- 27250303 TI - Calculated rotation-bending energy levels of CH5 (+) and a comparison with experiment. AB - We report J > 0 CH5 (+) levels computed by fixing stretch coordinates. They are computed by using a simple product basis, exploiting symmetry, and carefully parallelizing the calculation. The J > 0 CH5 (+) levels are compared with those obtained from other theoretical methods and with experimental ground state combination differences of Asvany et al. [Science, 347, 1346 (2015)]. If the assignment of Asvany et al. is correct, there are important differences between the levels we compute and those observed. We propose a different assignment of the experimental levels that reduces the maximum error from 34 to 2 cm(-1). The new assignment can only be correct if states of both parities exist in the experiment. Although, ro-vibrational levels of CH5 (+) cannot be associated with individual vibrational states, they do occur in blocks separated by gaps. PMID- 27250304 TI - Combined theoretical and experimental study of the valence, Rydberg and ionic states of fluorobenzene. AB - New photoelectron spectra (PES) and ultra violet (UV) and vacuum UV (VUV) absorption spectra of fluorobenzene recorded at higher resolution than previously, have been combined with mass-resolved (2 + 1) and (3 + 1) resonance enhanced multiphoton ionization (REMPI) spectra; this has led to the identification of numerous Rydberg states. The PES have been compared with earlier mass-analyzed threshold ionization and photoinduced Rydberg ionization (PIRI) spectra to give an overall picture of the ionic state sequence. The analysis of these spectra using both equations of motion with coupled cluster singles and doubles (EOM-CCSD) configuration interaction and time dependent density functional theory (TDDFT) calculations have been combined with vibrational analysis of both the hot and cold bands of the spectra, in considerable detail. The results extend several earlier studies on the vibronic coupling leading to conical intersections between the X(2)B1 and A(2)A2 states, and a further trio (B, C, and D) of states. The conical intersection of the X and A states has been explicitly identified, and its structure and energetics evaluated. The energy sequence of the last group is only acceptable to the present study if given as B(2)B2 RbOH((1)Sigma(+)) + e(-) of 4 * 10(-10) cm(3) s(-1) at 300 K has been calculated. This result agrees with the experimental rate constant of 2-1 (+2)*10(-10)cm(3)s(-1) obtained by Deiglmayr et al. [Phys. Rev. A 86, 043438 (2012)] for a temperature between 200 K and 600 K. A Langevin-based dynamics which depends on the crossing point between the anion (RbOH(-)) and neutral (RbOH) potential energy surfaces has been used. The calculations were performed using the ECP28MDF effective core potential to describe the rubidium atom at the CCSD(T) level of theory and extended basis sets. The effect of ECPs and basis set on the height of the crossing point, and hence the rate constant, has been investigated. The temperature dependence of the latter is also discussed. Preliminary work on the potential energy surface for the excited reaction channel Rb((2)P) + OH(-)((1)Sigma(+)) calculated at the CASSCF-icMRCI level of theory is presented. We qualitatively discuss the charge transfer and associative detachment reactions arising from this excited entrance channel. PMID- 27250306 TI - Synchrotron-based valence shell photoionization of CH radical. AB - We report the first experimental observations of X(+) (1)Sigma(+)<-X (2)Pi and a(+) (3)Pi<-X (2)Pi single-photon ionization transitions of the CH radical performed on the DESIRS beamline at the SOLEIL synchrotron facility. The radical was produced by successive hydrogen-atom abstractions on methane by fluorine atoms in a continuous microwave discharge flow tube. Mass-selected ion yields and photoelectron spectra were recorded as a function of photon energy using a double imaging photoelectron/photoion coincidence spectrometer. The ion yield appears to be strongly affected by vibrational and electronic autoionizations, which allow the observation of high Rydberg states of the neutral species. The photoelectron spectra enable the first direct determinations of the adiabatic ionization potential and the energy of the first triplet state of the cation with respect to its singlet ground state. This work also brings valuable information on the complex electronic structure of the CH radical and its cation and adds new observations to complement our understanding of Rydberg states and autoionization processes. PMID- 27250307 TI - Polarization response of clathrate hydrates capsulated with guest molecules. AB - Clathrate hydrates are characterized by their water cages encapsulating various guest atoms or molecules. The polarization effect of these guest-cage complexes was studied with combined density functional theory and finite-field calculations. An addition rule was noted for these systems whose total polarizability is approximately equal to the polarizability sum of the guest and the cage. However, their distributional polarizability computed with Hirshfeld partitioning scheme indicates that the guest-cage interaction has considerable influence on their polarization response. The polarization of encapsulated guest is reduced while the polarization of water cage is enhanced. The counteraction of these two opposite effects leads to the almost unchanged total polarizability. Further analysis reveals that the reduced polarizability of encapsulated guest results from the shielding effect of water cage against the external field and the enhanced polarizability of water cage from the enhanced bonding of hydrogen bonds among water molecules. Although the charge transfer through the hydrogen bonds is rather small in the water cage, the polarization response of clathrate hydrates is sensitive to the changes of hydrogen bonding strength. The guest encapsulation strengthens the hydrogen bonding network and leads to enhanced polarizability. PMID- 27250308 TI - Mutual neutralization of He(+) with the anions Cl(-), Br(-), I(-), and SF6 (.). AB - Mutual neutralization (MN) rate coefficients kMN for He(+) with the anions Cl(-), Br(-), I(-), and SF6 (-) are reported from 300 to 500 K. The measured rate coefficients may contain a contribution from transfer ionization, i.e., double ionization of the anion. The large rate coefficient for He(+) + SF6 (-) (2.4 * 10(-7) cm(3) s(-1) at 300 K) is consistent with earlier polyatomic MN results found to have a reduced mass dependence of MU(-1/2). Neutralization of He(+) by the atomic halides follows the trend observed earlier for Ne(+), Ar(+), Kr(+), and Xe(+) neutralized by atomic halides, kMN (Cl(-)) < kMN (Br(-)) < kMN (I(-)). Only an upper limit could be measured for the neutralization of He(+) by Cl(-). Predictions of the rate coefficients from a previously proposed simple model of atomic-atomic MN results are consistent with the present He(+)-halide rate coefficients. The temperature dependences are modestly negative for Br(-) and I( ), while that for SF6 (-) is small or negligible. PMID- 27250309 TI - Satellite bands of the RbCs molecule in the range of highly excited states. AB - We report on the observation of three RbCs satellite bands in the blue and green ranges of the visible spectrum. Absorption measurements are performed using all sapphire cell filled with a mixture of Rb and Cs. We compare high resolution absorption spectrum of Rb-Cs vapor mixture with pure Rb and Cs vapor spectra from the literature. After detailed analysis, the new satellite bands of RbCs molecule at 418.3 nm, 468.3, and 527.5 nm are identified. The origin of these bands is discussed by direct comparison with difference potentials derived from quantum chemistry calculations of RbCs potential energy curves. These bands originate from the lower Rydberg states of the RbCs molecule. This study thus provides further insight into photoassociation of lower Rydberg molecular states, approximately between Cs(7s) + Rb(5s) and Cs(6s) + Rb(6p) asymptotes, in ultracold gases. PMID- 27250310 TI - Kinetic theory of diffusion-limited nucleation. AB - We examine binary nucleation in the size and composition space {R,c} using the formalism of the multivariable theory [N. V. Alekseechkin, J. Chem. Phys. 124, 124512 (2006)]. We show that the variable c drops out of consideration for very large curvature of the new phase Gibbs energy with composition. Consequently nuclei around the critical size have the critical composition, which is derived from the condition of criticality for the canonical variables and is found not to depend on surface tension. In this case, nucleation kinetics can be investigated in the size space only. Using macroscopic kinetics, we determine the general expression for the condensation rate when growth is limited by bulk diffusion, which accounts for both diffusion and capillarity and exhibits a different dependence with the critical size, as compared with the interface-limited regime. This new expression of the condensation rate for bulk diffusion-limited nucleation is the counterpart of the classical interface-limited result. We then extend our analysis to multicomponent solutions. PMID- 27250311 TI - A new structural relaxation pathway of low-density amorphous ice. AB - Low-density amorphous (LDA) ice is involved in critical cosmological processes and has gained prominence as one of the at least two distinct amorphous forms of ice. Despite these accolades, we still have an incomplete understanding of the structural diversity that is encompassed within the LDA state and the dynamic processes that take place upon heating LDA. Heating the high-pressure ice VIII phase at ambient pressure is a remarkable example of temperature-induced amorphisation yielding LDA. We investigate this process in detail using X-ray diffraction and Raman spectroscopy and show that the LDA obtained from ice VIII is structurally different from the more "traditional" states of LDA which are approached upon thermal annealing. This new structural relaxation pathway involves an increase of structural order on the intermediate range length scale. In contrast with other LDA materials the local structure is more ordered initially and becomes slightly more disordered upon annealing. We also show that the cascade of phase transitions upon heating ice VIII at ambient pressure includes the formation of ice IX which may be connected with the structural peculiarities of LDA from ice VIII. Overall, this study shows that LDA is a structurally more diverse material than previously appreciated. PMID- 27250312 TI - Ice Ih anomalies: Thermal contraction, anomalous volume isotope effect, and pressure-induced amorphization. AB - Ice Ih displays several anomalous thermodynamic properties such as thermal contraction at low temperatures, an anomalous volume isotope effect (VIE) rendering the volume of D2O ice greater than that of H2O ice, and a pressure induced transition to the high-density amorphous (HDA) phase. Furthermore, the anomalous VIE increases with temperature, despite its quantum-mechanical origin. Here, embedded-fragment ab initio second-order many-body perturbation (MP2) theory in the quasiharmonic approximation (QHA) is applied to the Gibbs energy of an infinite, proton-disordered crystal of ice Ih at wide ranges of temperatures and pressures. The quantum effect of nuclei moving in anharmonic potentials is taken into account from first principles without any empirical or nonsystematic approximation to either the electronic or vibrational Hamiltonian. MP2 predicts quantitatively correctly the thermal contraction at low temperatures, which is confirmed to originate from the volume-contracting hydrogen-bond bending modes (acoustic phonons). It qualitatively reproduces (but underestimates) the thermal expansion at higher temperatures, caused by the volume-expanding hydrogen-bond stretching (and to a lesser extent librational) modes. The anomalous VIE is found to be the result of subtle cancellations among closely competing isotope effects on volume from all modes. Consequently, even ab initio MP2 with the aug-cc-pVDZ and aug-cc-pVTZ basis sets has difficulty reproducing this anomaly, yielding qualitatively varied predictions of the sign of the VIE depending on such computational details as the choice of the embedding field. However, the temperature growth of the anomalous VIE is reproduced robustly and is ascribed to the librational modes. These solid-state MP2 calculations, as well as MP2 Born Oppenheimer molecular dynamics, find a volume collapse and a loss of symmetry and long-range order in ice Ih upon pressure loading of 2.35 GPa or higher. Concomitantly, rapid softening of acoustic phonons is observed starting around 2 GPa. They constitute a computational detection of a mechanical instability in ice Ih and the resulting pressure-induced amorphization to HDA. PMID- 27250313 TI - A link between structure, diffusion and rotations of hydrogen bonding tracers in ionic liquids. AB - When solutes are small compared to the size of the ions in an ionic liquid, energetic heterogeneities associated with charge enhanced (stiff) and charge depleted (soft) nanoenvironments are sampled. In a recent article [J. C. Araque et al., J. Phys. Chem. B 119(23), 7015-7029 (2015)], we explored large deviations from Stokes-Einstein translational diffusion caused by such a heterogeneity. The current article is set to explore the effect of soft and stiff solvent environments (i.e., structure) on OH-bond rotations in the case of water and small alcohols in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (Im1,2 (+)NTf2 (-)). Is solute rotational dynamics heterogeneous? If so, are solute rotations and translations coupled in the sense that stiff and soft solvent environments hinder or speed up both types of dynamics? For the systems studied here, there appears to be a clear connection between translations, rotations, and stiff/soft solvent environments. We also discuss interesting asymmetries of the correlation between solutes with anions and cations. PMID- 27250314 TI - Lutetium(iii) aqua ion: On the dynamical structure of the heaviest lanthanoid hydration complex. AB - The structure and dynamics of the lutetium(iii) ion in aqueous solution have been investigated by means of a polarizable force field molecular dynamics (MD). An 8 fold square antiprism (SAP) geometry has been found to be the dominant configuration of the lutetium(iii) aqua ion. Nevertheless, a low percentage of 9 fold complexes arranged in a tricapped trigonal prism (TTP) geometry has been also detected. Dynamic properties have been explored by carrying out six independent MD simulations for each of four different temperatures: 277 K, 298 K, 423 K, 632 K. The mean residence time of water molecules in the first hydration shell at room temperature has been found to increase as compared to the central elements of the lanthanoid series in agreement with previous experimental findings. Water exchange kinetic rate constants at each temperature and activation parameters of the process have been determined from the MD simulations. The obtained structural and dynamical results suggest that the water exchange process for the lutetium(iii) aqua ion proceeds with an associative mechanism, in which the SAP hydration complex undergoes temporary structural changes passing through a 9-fold TTP intermediate. Such results are consistent with the water exchange mechanism proposed for heavy lanthanoid atoms. PMID- 27250316 TI - A fast dynamic mode in rare earth based glasses. AB - Metallic glasses (MGs) usually exhibit only slow beta-relaxation peak, and the signature of the fast dynamic is challenging to be observed experimentally in MGs. We report a general and unusual fast dynamic mode in a series of rare earth based MGs manifested as a distinct fast beta'-relaxation peak in addition to slow beta-relaxation and alpha-relaxation peaks. We show that the activation energy of the fast beta'-relaxation is about 12RTg and is equivalent to the activation of localized flow event. The coupling of these dynamic processes as well as their relationship with glass transition and structural heterogeneity is discussed. PMID- 27250315 TI - Molecular mobility in glassy dispersions. AB - Dielectric spectroscopy was used to characterize the structural relaxation in pharmaceutical dispersions containing nifedipine (NIF) and either poly(vinyl) pyrrolidone (PVP) or hydroxypropyl methylcellulose acetate succinate (HPMCAS). The shape of the dielectric response (permittivity versus log time) curve was observed to be independent of temperature. Thus, for the pure NIF as well as the dispersions, the validity of the time-temperature superposition principle was established. Furthermore, though the shape of the full dielectric response varied with polymer concentration, the regime related to the alpha- or structural relaxation was found to superimpose for the dispersions, though not with the response of the NIF itself. Hence, there is a limited time-temperature concentration superposition for these systems as well. Therefore, in this polymer concentration range, calculation of long relaxation times in these glass-forming systems becomes possible. We found that strong drug-polymer hydrogen bonding interactions improved the physical stability (i.e., delayed crystallization) by reducing the molecular mobility. The strength of hydrogen bonding, structural relaxation time, and crystallization followed the order: NIF-PV P>NIF-HPMCAS>NIF. With an increase in polymer concentration, the relaxation times were longer indicating a decrease in molecular mobility. The temperature dependence of relaxation time, in other words fragility, was independent of polymer concentration. This is the first application of the superposition principle to characterize structural relaxation in glassy pharmaceutical dispersions. PMID- 27250317 TI - Influence of the exchange and correlation functional on the structure of amorphous InSb and In3SbTe2 compounds. AB - We have investigated the structural, vibrational, and electronic properties of the amorphous phase of InSb and In3SbTe2 compounds of interest for applications in phase change non-volatile memories. Models of the amorphous phase have been generated by quenching from the melt by molecular dynamics simulations based on density functional theory. In particular, we have studied the dependence of the structural properties on the choice of the exchange-correlation functional. It turns out that the use of the Becke-Lee-Yang-Parr functional provides models with a much larger fraction of In atoms in a tetrahedral bonding geometry with respect to previous results obtained with the most commonly used Perdew-Becke-Ernzerhof functional. This outcome is at odd with the properties of Ge2Sb2Te5 phase change compound for which the two exchange-correlation functionals yield very similar results on the structure of the amorphous phase. PMID- 27250318 TI - Glassy dynamics of model colloidal polymers: The effect of "monomer" size. AB - In recent years, attempts have been made to assemble colloidal particles into chains, which are termed "colloidal polymers." An apparent difference between molecular and colloidal polymers is the "monomer" size. Here, we propose a model to represent the variation from molecular polymer to colloidal polymer and study the quantitative differences in their glassy dynamics. For chains, two incompatible local length scales, i.e., monomer size and bond length, are manifested in the radial distribution function and intramolecular correlation function. The mean square displacement of monomers exhibits Rouse-like sub diffusion at intermediate time/length scale and the corresponding exponent depends on the volume fraction and the monomer size. We find that the threshold volume fraction at which the caging regime emerges can be used as a rescaling unit so that the data of localization length versus volume fraction for different monomer sizes can gather close to an exponential curve. The increase of monomer size effectively increases the hardness of monomers and thus makes the colloidal polymers vitrify at lower volume fraction. Static and dynamic equivalences between colloidal polymers of different monomer sizes have been discussed. In the case of having the same peak time of the non-Gaussian parameter, the motion of monomers of larger size is much less non-Gaussian. The mode-coupling critical exponents for colloidal polymers are in agreement with that of flexible bead spring chains. PMID- 27250319 TI - Adsorption of anionic and non-ionic surfactants on carbon nanotubes in water with dissipative particle dynamics simulation. AB - The morphology of surfactants physically adsorbed on the surface of carbon nanotubes (CNTs) has a significant impact on the dispersion of CNTs in the solution. The adsorption of the surfactants alfoterra 123-8s (AF) and tergitol 15 s-40 (TG) on CNTs was investigated with dissipative particle dynamics (DPD) simulations, as well as the behavior of the binary surfactant system with CNTs. Properties of surfactants (i.e., critical micelle concentration, aggregation number, shape and size of micelle, and diffusivity) in water were determined to validate the simulation model. Results indicated that the assembly of surfactants (AF and TG) on CNTs depends on the interaction of the surfactant tail and the CNT surface, where surfactants formed mainly hemimicellar structures. For surfactants in solution, most micelles had spherical shape. The particles formed by the CNT and the adsorbed surfactant became hydrophilic, due to the outward orientation of the head groups of the surfactants that formed monolayer adsorption. In the binary surfactant system, the presence of TG on the CNT surface provided a considerable hydrophilic steric effect, due to the EO groups of TG molecules. It was also seen that the adsorption of AF was more favorable than TG on the CNT surface. Diffusion coefficients for the surfactants in the bulk and surface diffusion on the CNT were calculated. These results are applicable, in a qualitative sense, to the more general case of adsorption of surfactants on the hydrophobic surface of cylindrically shaped nanoscale objects. PMID- 27250320 TI - Target search kinetics of self-propelled particles in a confining domain. AB - We present a numerical investigation of the search kinetics of self-propelled particles (SPPs) to a target located at the center or at the boundary of a confining domain. When searching a target located at the center of a circular confining domain, the search efficiency of SPPs is improved compared to that of Brownian particles if the rotational diffusion is not too slow. In this case, the mean search time tau could be minimized with proper combinations of the characteristic rotation time tautheta and the self-propulsion velocity v0. It is further shown to be a consequence of the interplay between the enhanced diffusion and the thigmotactism (boundary-following behavior) of SPPs due to the self propulsion. However, for a target located at the boundary of the circular confining domain, we find that the search process is continuing to be accelerated with increasing tautheta or v0. Our results highlight the role of the target position in the search kinetics, and open up new opportunities to optimize the search process of SPPs by taking accurate controls over their motions. PMID- 27250321 TI - Density functional study on the mechanism for the highly active palladium monolayer supported on titanium carbide for the oxygen reduction reaction. AB - The adsorption, diffusion, and dissociation of O2 on the palladium monolayer supported on TiC(001) surface, MLPd/TiC(001), are investigated using ab initio density functional theory calculations. Strong adhesion of palladium monolayer to the TiC(001) support, accompanied by a modification of electronic structure of the supported palladium, is evidenced. Compared with Pt(111) surface, the MLPd/TiC(001) can enhance the adsorption of O2, leading to comparable dissociation barrier and a smaller diffusion barrier of O2. Whilst the adsorption strength of atomic O (the dissociation product of O2) on MLPd/TiC(001) is similar to that on the Pt(111) surface, possessing high mobility, our theoretical results indicate that MLPd/TiC(001) may serve as a good catalyst for the oxygen reduction reaction. PMID- 27250322 TI - Search for giant magnetic anisotropy in transition-metal dimers on defected hexagonal boron nitride sheet. AB - Structural and magnetic properties of many transition-metal dimers embedded in a defected hexagonal boron nitride monolayer are investigated through density functional calculations to search for systems with magnetic anisotropy energies (MAEs) larger than 30meV. In particular, Ir-Ir@Dh-BN is found to have both large MAE (~126 meV) and high structural stability against dissociation and diffusion, and it hence can serve as magnetic unit in spintronics and quantum computing devices. This giant MAE mainly results from the spin orbit coupling and the magnetization of the upper Ir atom, which is in a rather isolated environment. PMID- 27250323 TI - Surface tension of ab initio liquid water at the water-air interface. AB - We report calculations on the surface tension of the water-air interface using ab initio molecular dynamics (AIMD) simulations. We investigate the influence of the cell size on surface tension of water from force field molecular dynamics simulations. We find that the calculated surface tension increases with increasing simulation cell size, thereby illustrating that a correction for finite size effects is essential for small systems that are customary in AIMD simulations. Moreover, AIMD simulations reveal that the use of a double-zeta basis set overestimates the experimentally measured surface tension due to the Pulay stress while more accurate triple and quadruple-zeta basis sets give converged results. We further demonstrate that van der Waals corrections critically affect the surface tension. AIMD simulations without the van der Waals correction substantially underestimate the surface tension while the van der Waals correction with the Grimme's D2 technique results in a value for the surface tension that is too high. The Grimme's D3 van der Waals correction provides a surface tension close to the experimental value. Whereas the specific choices for the van der Waals correction and basis sets critically affect the calculated surface tension, the surface tension is remarkably insensitive to the details of the exchange and correlation functionals, which highlights the impact of long-range interactions on the surface tension. Our simulated values provide important benchmarks, both for improving van der Waals corrections and AIMD simulations of aqueous interfaces. PMID- 27250324 TI - Extent of hydrogen coverage of Si(001) under chemical vapor deposition conditions from ab initio approaches. AB - The extent of hydrogen coverage of the Si(001) c(4 * 2) surface in the presence of hydrogen gas has been studied with dispersion corrected density functional theory. Electronic energy contributions are well described using a hybrid functional. The temperature dependence of the coverage in thermodynamic equilibrium was studied computing the phonon spectrum in a supercell approach. As an approximation to these demanding computations, an interpolated phonon approach was found to give comparable accuracy. The simpler ab initio thermodynamic approach is not accurate enough for the system studied, even if corrections by the Einstein model for surface vibrations are considered. The on-set of H2 desorption from the fully hydrogenated surface is predicted to occur at temperatures around 750 K. Strong changes in hydrogen coverage are found between 1000 and 1200 K in good agreement with previous reflectance anisotropy spectroscopy experiments. These findings allow a rational choice for the surface state in the computational treatment of chemical reactions under typical metal organic vapor phase epitaxy conditions on Si(001). PMID- 27250325 TI - Thermodynamic stability and structural properties of cluster crystals formed by amphiphilic dendrimers. AB - We pursue the goal of finding real-world examples of macromolecular aggregates that form cluster crystals, which have been predicted on the basis of coarse grained, ultrasoft pair potentials belonging to a particular mathematical class [B. M. Mladek et al., Phys. Rev. Lett. 46, 045701 (2006)]. For this purpose, we examine in detail the phase behavior and structural properties of model amphiphilic dendrimers of the second generation by means of monomer-resolved computer simulations. On augmenting the density of these systems, a fluid comprised of clusters that contain several overlapping and penetrating macromolecules is spontaneously formed. Upon further compression of the system, a transition to multi-occupancy crystals takes place, the thermodynamic stability of which is demonstrated by means of free-energy calculations, and where the FCC is preferred over the BCC-phase. Contrary to predictions for coarse-grained theoretical models in which the particles interact exclusively by effective pair potentials, the internal degrees of freedom of these molecules cause the lattice constant to be density-dependent. Furthermore, the mechanical stability of monodisperse BCC and FCC cluster crystals is restricted to a bounded region in the plane of cluster occupation number versus density. The structural properties of the dendrimers in the dense crystals, including their overall sizes and the distribution of monomers are also thoroughly analyzed. PMID- 27250326 TI - The efficiency of self-phoretic propulsion mechanisms with surface reaction heterogeneity. AB - We consider the efficiency of self-phoretic colloidal particles (swimmers) as a function of the heterogeneity in the surface reaction rate. The set of fluid, species, and electrostatic continuity equations is solved analytically using a linearization and numerically using a finite-element method. To compare spherical swimmers of different size and with heterogeneous catalytic conversion rates, a "swimmer efficiency" functional eta is introduced. It is proven that in order to obtain maximum swimmer efficiency, the reactivity has to be localized at the pole(s). Our results also shed light on the sensitivity of the propulsion speed to details of the surface reactivity, a property that is notoriously hard to measure. This insight can be utilized in the design of new self-phoretic swimmers. PMID- 27250327 TI - Solvent and solute ingress into hydrogels resolved by a combination of imaging techniques. AB - Using simultaneous neutron, fluorescence, and optical brightfield transmission imaging, the diffusion of solvent, fluorescent dyes, and macromolecules into a crosslinked polyacrylamide hydrogel was investigated. This novel combination of different imaging techniques enables us to distinguish the movements of the solvent and fluorescent molecules. Additionally, the swelling or deswelling of the hydrogels can be monitored. From the sequence of images, dye and solvent concentrations were extracted spatially and temporally resolved. Diffusion equations and different boundary conditions, represented by different models, were used to quantitatively analyze the temporal evolution of these concentration profiles and to determine the diffusion coefficients of solvent and solutes. Solute size and network properties were varied and their effect was investigated. Increasing the crosslinking ratio or partially drying the hydrogel was found to hinder solute diffusion due to the reduced pore size. By contrast, solvent diffusion seemed to be slightly faster if the hydrogel was only partially swollen and hence solvent uptake enhanced. PMID- 27250328 TI - Dynamic colloidal assembly pathways via low dimensional models. AB - Here we construct a low-dimensional Smoluchowski model for electric field mediated colloidal crystallization using Brownian dynamic simulations, which were previously matched to experiments. Diffusion mapping is used to infer dimensionality and confirm the use of two order parameters, one for degree of condensation and one for global crystallinity. Free energy and diffusivity landscapes are obtained as the coefficients of a low-dimensional Smoluchowski equation to capture the thermodynamics and kinetics of microstructure evolution. The resulting low-dimensional model quantitatively captures the dynamics of different assembly pathways between fluid, polycrystal, and single crystals states, in agreement with the full N-dimensional data as characterized by first passage time distributions. Numerical solution of the low-dimensional Smoluchowski equation reveals statistical properties of the dynamic evolution of states vs. applied field amplitude and system size. The low-dimensional Smoluchowski equation and associated landscapes calculated here can serve as models for predictive control of electric field mediated assembly of colloidal ensembles into two-dimensional crystalline objects. PMID- 27250329 TI - Divalent cation shrinks DNA but inhibits its compaction with trivalent cation. AB - Our observation reveals the effects of divalent and trivalent cations on the higher-order structure of giant DNA (T4 DNA 166 kbp) by fluorescence microscopy. It was found that divalent cations, Mg(2+) and Ca(2+), inhibit DNA compaction induced by a trivalent cation, spermidine (SPD(3+)). On the other hand, in the absence of SPD(3+), divalent cations cause the shrinkage of DNA. As the control experiment, we have confirmed the minimum effect of monovalent cation, Na(+) on the DNA higher-order structure. We interpret the competition between 2+ and 3+ cations in terms of the change in the translational entropy of the counterions. For the compaction with SPD(3+), we consider the increase in translational entropy due to the ion-exchange of the intrinsic monovalent cations condensing on a highly charged polyelectrolyte, double-stranded DNA, by the 3+ cations. In contrast, the presence of 2+ cation decreases the gain of entropy contribution by the ion-exchange between monovalent and 3+ ions. PMID- 27250330 TI - Understanding nucleic acid structural changes by comparing wide-angle x-ray scattering (WAXS) experiments to molecular dynamics simulations. AB - Wide-angle x-ray scattering (WAXS) is emerging as a powerful tool for increasing the resolution of solution structure measurements of biomolecules. Compared to its better known complement, small angle x-ray scattering (SAXS), WAXS targets higher scattering angles and can enhance structural studies of molecules by accessing finer details of solution structures. Although the extension from SAXS to WAXS is easy to implement experimentally, the computational tools required to fully harness the power of WAXS are still under development. Currently, WAXS is employed to study structural changes and ligand binding in proteins; however, the methods are not as fully developed for nucleic acids. Here, we show how WAXS can qualitatively characterize nucleic acid structures as well as the small but significant structural changes driven by the addition of multivalent ions. We show the potential of WAXS to test all-atom molecular dynamics (MD) simulations and to provide insight into understanding how the trivalent ion cobalt(III) hexammine (CoHex) affects the structure of RNA and DNA helices. We find that MD simulations capture the RNA structural change that occurs due to addition of CoHex. PMID- 27250331 TI - Lattice model for amyloid peptides: OPEP force field parametrization and applications to the nucleus size of Alzheimer's peptides. AB - Coarse-grained protein lattice models approximate atomistic details and keep the essential interactions. They are, therefore, suitable for capturing generic features of protein folding and amyloid formation at low computational cost. As our aim is to study the critical nucleus sizes of two experimentally well characterized peptide fragments Abeta16-22 and Abeta37-42 of the full length Abeta1-42 Alzheimer's peptide, it is important that simulations with the lattice model reproduce all-atom simulations. In this study, we present a comprehensive force field parameterization based on the OPEP (Optimized Potential for Efficient protein structure Prediction) force field for an on-lattice protein model, which incorporates explicitly the formation of hydrogen bonds and directions of side chains. Our bottom-up approach starts with the determination of the best lattice force parameters for the Abeta16-22 dimer by fitting its equilibrium parallel and anti-parallel beta-sheet populations to all-atom simulation results. Surprisingly, the calibrated force field is transferable to the trimer of Abeta16 22 and the dimer and trimer of Abeta37-42. Encouraged by this finding, we characterized the free energy landscapes of the two decamers. The dominant structure of the Abeta16-22 decamer matches the microcrystal structure. Pushing the simulations for aggregates between 4-mer and 12-mer suggests a nucleus size for fibril formation of 10 chains. In contrast, the Abeta37-42 decamer is largely disordered with mixed by parallel and antiparallel chains, suggesting that the nucleus size is >10 peptides. Our refined force field coupled to this on-lattice model should provide useful insights into the critical nucleation number associated with neurodegenerative diseases. PMID- 27250332 TI - Effect of non-specific interactions on formation and stability of specific complexes. AB - We introduce a simple model to describe the interplay between specific and non specific interactions. We study the influence of various physical factors on the static and dynamic properties of the specific interactions of our model and show that contrary to intuitive expectations, non-specific interactions can assist in the formation of specific complexes and increase their stability. We then discuss the relevance of these results for biological systems. PMID- 27250333 TI - Thermodynamics of complex structures formed between single-stranded DNA oligomers and the KH domains of the far upstream element binding protein. AB - The noncovalent interaction between protein and DNA is responsible for regulating the genetic activities in living organisms. The most critical issue in this problem is to understand the underlying driving force for the formation and stability of the complex. To address this issue, we have performed atomistic molecular dynamics simulations of two DNA binding K homology (KH) domains (KH3 and KH4) of the far upstream element binding protein (FBP) complexed with two single-stranded DNA (ss-DNA) oligomers in aqueous media. Attempts have been made to calculate the individual components of the net entropy change for the complexation process by adopting suitable statistical mechanical approaches. Our calculations reveal that translational, rotational, and configurational entropy changes of the protein and the DNA components have unfavourable contributions for this protein-DNA association process and such entropy lost is compensated by the entropy gained due to the release of hydration layer water molecules. The free energy change corresponding to the association process has also been calculated using the Free Energy Perturbation (FEP) method. The free energy gain associated with the KH4-DNA complex formation has been found to be noticeably higher than that involving the formation of the KH3-DNA complex. PMID- 27250334 TI - Publisher's Note: "New ab initio adiabatic potential energy surfaces and bound state calculations for the singlet ground X(1)A1 and excited C(1)B2(2(1)A(')) states of SO2" [J. Chem. Phys. 144, 174301 (2016)]. PMID- 27250335 TI - How the initial level of visibility and limited resource affect the evolution of cooperation. AB - This work sheds important light on how the initial level of visibility and limited resource might affect the evolution of the players' strategies under different network structure. We perform the prisoner's dilemma game in the lattice network and the scale-free network, the simulation results indicate that the average density of death in lattice network decreases with the increases of the initial proportion of visibility. However, the contrary phenomenon is observed in the scale-free network. Further results reflect that the individuals' payoff in lattice network is significantly larger than the one in the scale-free network. In the lattice network, the visibility individuals could earn much more than the invisibility one. However, the difference is not apparent in the scale free network. We also find that a high Successful-Defection-Payoff (SDB) and a rich natural environment have relatively larger deleterious cooperation effects. A high SDB is beneficial to raising the level of visibility in the heterogeneous network, however, that has adverse visibility consequences in homogeneous network. Our result reveals that players are more likely to cooperate voluntarily under homogeneous network structure. PMID- 27250336 TI - The Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS): a Pre test Study. AB - BACKGROUND: Returning to and continuing work is important to many cancer survivors, but also represents a challenge. We know little about subjective work outcomes and how cancer survivors perceive being returned to work. Therefore, we developed the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ CS). Our aim was to pre-test the items of the initial QWLQ-CS on acceptability and comprehensiveness. In addition, item retention was performed by pre-assessing the relevance scores and response distributions of the items in the QWLQ-CS. METHODS: Semi-structured interviews were conducted after cancer survivors, who had returned to work, filled in the 102 items of the QWLQ-CS. To improve acceptability and comprehensiveness, the semi-structured interview inquired about items that were annoying, difficult, confusing, twofold or redundant. If cancer survivors had difficulty explaining their opinion or emotion about an item, the interviewer used verbal probing technique to investigate the cancer survivor's underlying thoughts. The cancer survivors' comments on the items were analysed, and items were revised accordingly. Decisions on item retention regarding the relevance of items and the response distributions were made by means of pre-set decision rules. RESULTS: The 19 cancer survivors (53 % male) had a mean age of 51 +/- 11 years old. They were diagnosed between 2009 and 2013 with lymphoma, leukaemia, prostate cancer, breast cancer, or colon cancer. Acceptability of the QWLQ-CS was good - none of the items were annoying - but 73 items were considered difficult, confusing, twofold or redundant. To improve acceptability, for instance, the authors replaced the phrase 'disease' with 'health situation' in several items. Consequently, comprehensiveness was improved by the authors rephrasing and adjusting items by adding clarifying words, such as 'in the work situation'. The pre-assessment of the relevance scores resulted in a sufficient number of cancer survivors indicating the items as relevant to their quality of working life, and no evident indication for uneven response distributions. Therefore, all items were retained. CONCLUSIONS: The 104 items of the preliminary QWLQ-CS were found relevant, acceptable and comprehensible by cancer survivors who have returned to work. The QWLQ-CS is now suitable for larger sample sizes of cancer survivors, which is necessary to test the psychometric properties of this questionnaire. PMID- 27250337 TI - Visceral symptoms as a key diagnostic sign for the early infantile form of Niemann-Pick disease type C in a Russian patient: a case report. AB - BACKGROUND: Niemann-Pick disease type C is a rare metabolic disease characterized by progressive neurological deterioration with childhood onset, and often results in premature mortality. Niemann-Pick disease type C has an extremely heterogeneous clinical presentation with a wide range of visceral and neurological signs and symptoms that are not specific to the disease, and which progress over varied periods of time. The incidence and epidemiology of Niemann Pick disease type C in Russia have not been characterized. We report the case of a Russian newborn with early-infantile onset Niemann-Pick disease type C who displayed prolonged neonatal jaundice and hepatosplenomegaly. CASE PRESENTATION: A 5-year-old white boy born to non-consanguineous Russian parents was originally diagnosed with galactosemia at the age of 2 months based on a raised blood galactose level. A galactose-free and lactose-free diet resulted in achievement of a normal galactose level, but hepatosplenomegaly and cholestatic signs persisted. Liver biopsy results hinted at possible Niemann-Pick disease type C, but differential diagnostic investigations for progressive familial intrahepatic cholestasis type 2 (Byler syndrome) indicated a heterozygous genotype suggestive of this disease. Further, progressive neurological symptoms prompted additional genetic analyses for possible Niemann-Pick disease type C, from which an as-yet unreported combination of known NPC1 gene mutations was identified, and a final diagnosis of Niemann-Pick disease type C was established. The patient subsequently developed typical neurological symptoms of early-infantile Niemann Pick disease type C, including vertical supranuclear ophthalmoparesis and cerebellar ataxia. Miglustat therapy was initiated 2.5 years ago, and some improvements in movement and speech have since been observed. CONCLUSIONS: This case illustrates the continued challenges associated with diagnosing Niemann-Pick disease type C based on the appearance of nonspecific cholestatic symptoms. Based on this case we recommend examination of all newborns and children who display unexplained cholestasis or isolated splenomegaly/hepatosplenomegaly during the first months of life for other signs of possible Niemann-Pick disease type C. PMID- 27250338 TI - Close-to-community providers of health care: increasing evidence of how to bridge community and health systems. PMID- 27250339 TI - Glacial melting: an overlooked threat to Antarctic krill. AB - Strandings of marine animals are relatively common in marine systems. However, the underlying mechanisms are poorly understood. We observed mass strandings of krill in Antarctica that appeared to be linked to the presence of glacial meltwater. Climate-induced glacial meltwater leads to an increased occurrence of suspended particles in the sea, which is known to affect the physiology of aquatic organisms. Here, we study the effect of suspended inorganic particles on krill in relation to krill mortality events observed in Potter Cove, Antarctica, between 2003 and 2012. The experimental results showed that large quantities of lithogenic particles affected krill feeding, absorption capacity and performance after only 24 h of exposure. Negative effects were related to both the threshold concentrations and the size of the suspended particles. Analysis of the stomach contents of stranded krill showed large quantities of large particles ( > 10(6 )MUm(3)), which were most likely mobilized by glacial meltwater. Ongoing climate induced glacial melting may impact the coastal ecosystems of Antarctica that rely on krill. PMID- 27250340 TI - MicroRNA-449a enhances radiosensitivity by downregulation of c-Myc in prostate cancer cells. AB - MicroRNAs (miRNAs) have been reported to be involved in DNA damage response induced by ionizing radiation (IR). c-Myc is reduced when cells treated with IR or other DNA damaging agents. It is unknown whether miRNAs participate in c-Myc downregulation in response to IR. In the present study, we found that miR-449a enhanced radiosensitivity in vitro and in vivo by targeting c-Myc in prostate cancer (LNCaP) cells. MiR-449a was upregulated and c-Myc was downregulated in response to IR in LNCaP cells. Overexpression of miR-449a or knockdown of c-Myc promoted the sensitivity of LNCaP cells to IR. By establishing c-Myc as a direct target of miR-449a, we revealed that miR-449a enhanced radiosensitivity by repressing c-Myc expression in LNCaP cells. Furthermore, we showed that miR-449a enhanced radiation-induced G2/M phase arrest by directly downregulating c-Myc, which controlled the Cdc2/CyclinB1 cell cycle signal by modulating Cdc25A. These results highlight an unrecognized mechanism of miR-449a-mediated c-Myc regulation in response to IR and may provide alternative therapeutic strategies for the treatment of prostate cancer. PMID- 27250341 TI - Single-Step Partial Purification of Intracellular beta-Galactosidase from Kluyveromyces lactis Using Microemulsion Droplets. AB - Partial purification of beta-galactosidase from the crude extract of Kluyveromyces lactis was carried out using water-in-isooctane microemulsions formed by the anionic surfactant, sodium di-ethylhexyl sulfosuccinate (Aerosol OT). In order to obtain the crude extract, yeast cells of K. lactis were disrupted by a cell disrupter and separated. The purification of beta galactosidase from the extract by a recently developed one-step reversed micellar (i.e., microemulsion-based) extraction method was then tested, by measuring total protein mass and enzyme activity in the product stream and by analyzing its composition using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) and gel filtration chromatography. Effects of salt concentration, protein concentration, and pH on the extraction were investigated. Using this approach, a 5.4-fold purification of beta-galactosidase was achieved with 96 % total activity recovery, using a feed containing crude extract and 50 mM K-phosphate buffer (pH 7.5) and 50 mM KCl. Gel filtration chromatography showed that the single extraction was successful at removing low molecular weight impurity proteins (molecular weight (MW) < 42 kDa) from the crude extract. PMID- 27250342 TI - In situ Removal of Hydrogen Sulfide During Biogas Fermentation at Microaerobic Condition. AB - In this paper, rice straw was used as a raw material to produce biogas by anaerobic batch fermentation at 35 degrees C (mesophilic) or 55 degrees C (thermophilic). The hydrogen sulfide in biogas can be converted to S0 or sulfate and removed in-situ under micro-oxygen environment. Trace oxygen was conducted to the anaerobic fermentation tank in amount of 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, or 10.0 times stoichiometric equivalence, respectively, and the control experiment without oxygen addition was carried out. The results showed that the initial H2S concentrations of biogas are about 3235 +/- 185 mg/m3 (mesophilic) or 3394 +/- 126 mg/m3 (thermophilic), respectively. The desulfurization efficiency is 72.3 % (mesophilic) or 65.6 % (thermophilic), respectively, with oxygen addition by stoichiometric relation. When the oxygen feeded in amount of 2~4 times, theoretical quantity demanded the removal efficiency of hydrogen sulfide could be over 92 %, and the oxygen residue in biogas could be maintained less than 0.5 %, which fit the requirement of biogas used as vehicle fuel or combined to the grid. Though further more oxygen addition could promote the removal efficiency of hydrogen sulfide (about 93.6 %), the oxygen residue in biogas would be higher than the application limit concentration (0.5 %). Whether mesophilic or thermophilic fermentation with the extra addition of oxygen, there were no obvious changes in the gas production and methane concentration. In conclusion, in-situ desulfurization can be achieved in the anaerobic methane fermentation system under micro-oxygen environment. In addition, air could be used as a substitute oxygen resource on the situation without strict demand for the methane content of biogas. PMID- 27250343 TI - Energy transfer from an individual silica nanoparticle to graphene quantum dots and resulting enhancement of photodetector responsivity. AB - Forster resonance energy transfer (FRET), referred to as the transfer of the photon energy absorbed in donor to acceptor, has received much attention as an important physical phenomenon for its potential applications in optoelectronic devices as well as for the understanding of some biological systems. If one-atom thick graphene is used for donor or acceptor, it can minimize the separation between donor and acceptor, thereby maximizing the FRET efficiency (EFRET). Here, we report first fabrication of a FRET system composed of silica nanoparticles (SNPs) and graphene quantum dots (GQDs) as donors and acceptors, respectively. The FRET from SNPs to GQDs with an EFRET of ~78% is demonstrated from excitation dependent photoluminescence spectra and decay curves. The photodetector (PD) responsivity (R) of the FRET system at 532 nm is enhanced by 10(0)~10(1)/10(2)~10(3) times under forward/reverse biases, respectively, compared to the PD containing solely GQDs. This remarkable enhancement is understood by network-like current paths formed by the GQDs on the SNPs and easy transfer of the carriers generated from the SNPs into the GQDs due to their close attachment. The R is 2~3 times further enhanced at 325 nm by the FRET effect. PMID- 27250344 TI - Current status and recent advances of gene therapy in hematological diseases. PMID- 27250346 TI - A Prospective Investigation of Affect, the Desire to Gamble, Gambling Motivations and Gambling Behavior in the Mood Disorders. AB - Time-sampling methodology was implemented to examine the prospective associations between affect, desire to gamble, and gambling behavior in individuals diagnosed with a mood disorder. Thirty (9 male, 21 female) adults with a lifetime diagnosis of a depressive or bipolar disorder diagnosis who endorsed current gambling and lifetime gambling harm participated in the present study. Participants completed electronic diary entries of their current affective state, desire to gamble, and gambling behavior for 30 consecutive days. Hierarchical linear modelling revealed that affect was not a predictor of gambling behavior. Instead, affect predicted the desire to gamble, with high levels of sadness and arousal independently predicting an increased desire to gamble. Desire to gamble predicted actual gambling behavior. There were no differences across diagnostic groups in terms of gambling motivations at baseline; however, during the 30-day period, participants with bipolar disorder endorsed gambling to cope with negative affect more often than did participants with depressive disorder, whereas those with depressive disorder more often endorsed gambling for social reasons or enhancement of positive affect. The present findings provide evidence that negative affect is not directly related to actual gambling behavior, and suggest that affective states rather impact the desire to gamble. PMID- 27250345 TI - Regulation of hematopoietic development by ZBTB transcription factors. AB - Hematopoietic development is governed by the coordinated expression of lineage- and differentiation stage-specific genes. Transcription factors play major roles in this process and their perturbation may underlie hematologic and immunologic disorders. Nearly 1900 transcription factors are encoded in the human genome: of these, 49 BTB (for broad-complex, tram-track and bric a brac)-zinc finger transcription factors referred to as ZBTB or POK proteins have been identified. ZBTB proteins, including BCL6, PLZF, ThPOK and LRF, exhibit a broad spectrum of functions in normal and malignant hematopoiesis. This review summarizes developmental and molecular functions of ZBTB proteins relevant to hematology. PMID- 27250348 TI - Feasibility of ultra low-dose thallium stress-redistribution protocol including prone imaging in obese patients using CZT camera. AB - High efficiency cadmium-zinc-telluride (CZT) cameras provide an opportunity to lower the injected activities of radiopharmaceuticals for single photon emission tomography (SPECT) myocardial perfusion imaging (MPI). The limits for reducing activities of thallium have not been determined, particularly in obese patients. After an injection of 0.7 megabecquerel (MBq) of thallium/kg, we collected an average 1.5 million counts for the 10-min acquisition in a pilot cohort of ten patients. After extrapolation, we reduced the administered activity to 0.5 MBq/kg to obtain the expected 1 million counts. We studied the image quality in 124 patients (86 men, 43 obese with body mass index over 30 kg/m2) referred for MPI. The quality of images was assessed by a number of recorded counts and visually by a four-grade scale (one-poor quality, four-excellent quality). In non-obese and obese patients, the average number of recorded counts was 1.1 vs. 1.07 million counts for the 10-min stress acquisition, 1.04 vs. 1.06 million counts for the 13 min rest acquisition, and the average quality score was 3.97 vs. 3.90, respectively (p = NS).The mean administered activity was 39.2 +/- 7 MBq for non obese and 48.7 +/- 6 for obese patients (p < 0.0001), and the calculated effective dose was 4.0 +/- 0.7 and 4.9 +/- 0.6 mSv respectively (p < 0.0001). The ultra-low-dose thallium stress-redistribution protocol, including post-stress prone imaging, provides good quality of images with a low radiation burden, even in obese patients. PMID- 27250350 TI - Peripheral artery disease and blood pressure profile abnormalities in hemodialysis patients. AB - BACKGROUND: Patients undergoing chronic hemodialysis (HD) are at increased risk for peripheral artery disease (PAD). Both ankle-brachial index (ABI) and ambulatory blood pressure monitoring (ABPM) in the interdialytic period have been shown to be strong predictors of all-cause mortality. METHODS: This cross sectional study investigated the relationship between ABPM profile and ABI in 81 HD patients. ABPM was measured throughout a 44-h midweek interdialytic period. Pre-dialysis ABI was evaluated with a BOSO ABI device. An ABI value <0.9 or >=1.3 was defined as abnormal. RESULTS: In the whole study group (72 % males, mean age 67 +/- 14 years), there was an increase in BP (p < 0.05) and in systolic BP night/day ratio (n/dSR, p = 0.01) during the interdialytic period. Patients with abnormal ABI (n = 29) more frequently had a positive history for cerebrovascular accident and PAD and higher proBNP values than those with normal ABI (n = 52). No difference was detected among ABPM-derived components except for the n/dSR (p = 0.02). Patients with abnormal ABI showed a significantly increased n/dSR (p = 0.02) and ambulatory arterial stiffness index (AASI) (p = 0.006) on the second day compared to the first. Patients with n/dSR >1 during day 2 (n = 34) were older, showed significantly higher proBNP and AASI and were more likely to reveal abnormal ABI compared to those with a lower n/dSR (p = 0.006). CONCLUSIONS: Abnormal ABI in HD patients is associated to changes in interdialytic ABPM pattern, namely higher n/dSR on day 2. These data may indicate the pathophysiological mechanisms underlying the worse outcome observed in HD patients. PMID- 27250352 TI - Erratum to: Collaborative Care: a Pilot Study of a Child Psychiatry Outpatient Consultation Model for Primary Care Providers. PMID- 27250351 TI - Use of CRB-65 and quick Sepsis-related Organ Failure Assessment to predict site of care and mortality in pneumonia patients in the emergency department: a retrospective study. AB - BACKGROUND: The quick Sepsis-related Organ Failure Assessment (qSOFA) is a new screening system for sepsis that has prognostic performance equal to the full SOFA for patients with suspected infection outside the intensive care unit (ICU). The predictive value of qSOFA for mortality and site of care in patients with pneumonia is not clear. The present study was designed to investigate the predictive performance of qSOFA, CRB-65 (confusion, respiratory rate >=30/minute, systolic blood pressure <90 mmHg or diastolic blood pressure <=60 mmHg, age >=65 years) and CRB (confusion, respiratory rate >=30/minute, systolic blood pressure <90 mmHg or diastolic blood pressure <=60 mmHg) for mortality, hospitalisation and ICU admission in patients with pneumonia in the emergency department (ED). METHODS: Retrospective analyses of published data on adult patients with pneumonia presenting between January 2012 and May 2014 were undertaken. The prevalence of 28-day mortality, hospitalisation and ICU admission were compared with regard to qSOFA, CRB and CRB-65 scores. The performance of these three systems for predicting outcomes was compared. RESULTS: Of 1641 patients, 861 (53 %) were hospitalised (38 % in a general ward, 15 % in the ICU), and the remaining 780 (47 %) were treated as outpatients or were observed in the ED. Within 28 days, 547 (33 %) of 1641 patients died. CRB-65, CRB and qSOFA scores of patients who died, were hospitalised and admitted to the ICU than those who survived and were not hospitalised or admitted to the ICU (P < 0.001). AUC values of qSOFA for prediction of 28-day mortality, hospitalisation and ICU admission were similar to those for CRB-65 and CRB. Patients with qSOFA scores of 0, 1, 2 and 3 were associated with, respectively, mortality of 16.3 %, 24.4 %, 48.2 % and 68.4 %; prevalence of hospitalisation of 37.2 %, 47.4 %, 61.6 % and 73.7 %; and prevalence of ICU admission of 9.3 %, 9.1 %, 22.4 % and 45.3 %. Patients with qSOFA scores of 2 and 3 had a significantly higher prevalence of mortality and ICU admission than patients with identical CRB-65 scores. CONCLUSIONS: qSOFA is better than CRB-65 for identification of a high risk of mortality and requirement of ICU admission. PMID- 27250349 TI - Evaluation of a multi-arm multi-stage Bayesian design for phase II drug selection trials - an example in hemato-oncology. AB - BACKGROUND: Multi-Arm Multi-Stage designs aim at comparing several new treatments to a common reference, in order to select or drop any treatment arm to move forward when such evidence already exists based on interim analyses. We redesigned a Bayesian adaptive design initially proposed for dose-finding, focusing our interest in the comparison of multiple experimental drugs to a control on a binary criterion measure. METHODS: We redesigned a phase II clinical trial that randomly allocates patients across three (one control and two experimental) treatment arms to assess dropping decision rules. We were interested in dropping any arm due to futility, either based on historical control rate (first rule) or comparison across arms (second rule), and in stopping experimental arm due to its ability to reach a sufficient response rate (third rule), using the difference of response probabilities in Bayes binomial trials between the treated and control as a measure of treatment benefit. Simulations were then conducted to investigate the decision operating characteristics under a variety of plausible scenarios, as a function of the decision thresholds. RESULTS: Our findings suggest that one experimental treatment was less efficient than the control and could have been dropped from the trial based on a sample of approximately 20 instead of 40 patients. In the simulation study, stopping decisions were reached sooner for the first rule than for the second rule, with close mean estimates of response rates and small bias. According to the decision threshold, the mean sample size to detect the required 0.15 absolute benefit ranged from 63 to 70 (rule 3) with false negative rates of less than 2 % (rule 1) up to 6 % (rule 2). In contrast, detecting a 0.15 inferiority in response rates required a sample size ranging on average from 23 to 35 (rules 1 and 2, respectively) with a false positive rate ranging from 3.6 to 0.6 % (rule 3). CONCLUSION: Adaptive trial design is a good way to improve clinical trials. It allows removing ineffective drugs and reducing the trial sample size, while maintaining unbiased estimates. Decision thresholds can be set according to predefined fixed error decision rates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01342692 . PMID- 27250347 TI - Use of genome-editing tools to treat sickle cell disease. AB - Recent advances in genome-editing techniques have made it possible to modify any desired DNA sequence by employing programmable nucleases. These next-generation genome-modifying tools are the ideal candidates for therapeutic applications, especially for the treatment of genetic disorders like sickle cell disease (SCD). SCD is an inheritable monogenic disorder which is caused by a point mutation in the beta-globin gene. Substantial success has been achieved in the development of supportive therapeutic strategies for SCD, but unfortunately there is still a lack of long-term universal cure. The only existing curative treatment is based on allogeneic stem cell transplantation from healthy donors; however, this treatment is applicable to a limited number of patients only. Hence, a universally applicable therapy is highly desirable. In this review, we will discuss the three programmable nucleases that are commonly used for genome editing purposes: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9). We will continue by exemplifying uses of these methods to correct the sickle cell mutation. Additionally, we will present induction of fetal globin expression as an alternative approach to cure sickle cell disease. We will conclude by comparing the three methods and explaining the concerns about their use in therapy. PMID- 27250353 TI - Evaluation of Effectiveness of Embolization in Pelvic Congestion Syndrome with the New Vascular Occlusion Device (ArtVentive EOSTM): Preliminary Results. AB - PURPOSE: This study aimed to collect confirmatory data in support of the safety and efficiency of the ArtVentive EOSTM for the treatment of the pelvic congestion syndrome (PCS). This study was based on the OCCLUDE 1 Study Protocol approved by the Local Ethics Committee. MATERIALS AND METHODS: A prospective study carried out in June and July 2014 included 12 women aged 21-48 years (mean 31 years) scheduled for PCS embolization using the ArtVentive EOSTM. The inclusion criteria were clinical symptoms of PCS documented by transvaginal Doppler ultrasound and pelvic MRI. The pelvic pain was assessed by VAS score from 0 to 10 (0 represents lack of pain and 10 unbearable pain). A decrease in pelvic pain intensity based on the VAS was considered a clinical success. RESULTS: Successful embolization procedures with ArtVentive EOSTM were performed in 11 out of 12 patients. Nine patients underwent unilateral embolization of the left ovarian vein, and two had bilateral embolization of the ovarian veins. Complete ovarian vein occlusion confirmed by post deployment venography was achieved in all 11 patients. Procedures lasted from 19 to 45 min (average 28 min). Pain intensity decrease was observed in all 11 patients-a decrease of 5.6 points-from 7.3 pre-procedure to 1.6 post-embolization (standard deviation: 0.67). In one case, the left ovarian vein was injured by guide wire manipulation with contrast extravasation-not clinically significant. CONCLUSIONS: The use of ArtVentive EOSTM for occlusion of the ovarian veins in PCS patients is safe and effective. PMID- 27250355 TI - REcanalisation and Balloon-Oriented Puncture for Re-Insertion of Dialysis Catheter in Nonpatent Central Veins (REBORN). AB - PURPOSE: To describe a technique involving REcanalisation and Balloon-Oriented puncture for Re-insertion of dialysis catheter in Nonpatent central veins (REBORN) and to report long-term results. MATERIALS AND METHODS: This is a retrospective study of ten subjects in whom dialysis catheters were inserted using the REBORN technique from March 2012 to October 2014 and followed up till April 2016. Data on the duration of catheter usage, complications and reasons for removal were obtained. Seven patients had partially occluded lower internal jugular veins (IJV) recanalised in an antegrade fashion via a more cranial puncture. The balloon was then inflated at usual puncture site with an 18G needle. The collapsed balloon was cannulated with a guide wire, and both balloon and guide wire were advanced together into the superior vena cava. This was followed by tunnelled catheter placement using standard techniques. Two patients had catheters placed in the subclavian vein using a similar antegrade technique, and one patient had catheter placed via the left IJV following retrograde recanalisation from a right femoral puncture. RESULTS: Mean duration of catheter use was 278 days (range 32-503). Three catheters were removed due to matured arteriovenous accesses. Four patients had successful catheter change over the same subcutaneous track due to catheter malfunction. One catheter was removed after 7 months because of sepsis. No complications were reported. CONCLUSION: The REBORN technique allows for the preservation of central veins for future haemodialysis access, which can be challenging in patients requiring long-term dialysis. PMID- 27250356 TI - Bring Back 'Permanent' Filters. PMID- 27250354 TI - A Retrospective Comparison of Ultrasound-Assisted Catheter-Directed Thrombolysis and Catheter-Directed Thrombolysis Alone for Treatment of Proximal Deep Vein Thrombosis. AB - BACKGROUND: Recent studies have suggested that catheter-directed thrombolysis (CDT) reduces development of post-thrombotic syndrome (PTS). Ultrasound-assisted CDT (USCDT) might enhance the efficiency of thrombolysis. We aimed to compare USCDT with CDT on efficacy, safety, development of PTS, and quality of life after long-term follow-up. METHODS: We describe a retrospective case series of 94 consecutive patients admitted with iliofemoral or more proximal deep vein thrombosis (DVT) to the University Hospital from 2002 to 2011, treated either with CDT or USCDT. Scheduled follow-up visits took place between April 2013 and January 2014. Venography measured the degree of residual luminal obstruction of the affected veins. Each patient completed the Short Form 36-item health survey assessment and the Venous Insufficiency Epidemiological and Economic Study Quality of Life/Symptoms questionnaires. PTS was assessed using the Villalta scale. RESULTS: Risk factors of DVT were equally distributed between groups. In the USCDT group, we observed a significant decline in the duration of thrombolytic treatment (<48 h: 27 vs. 10 %), shortened hospital stay (median 6.0 days (IQR 5.0-9.0) vs. 8.0 (IQR 5.8-12.0)), and less implantation of (intravenous) stents (30 vs. 55 %). There was no difference in patency (76 vs. 79 % fully patent), prevalence of PTS (52 vs. 55 %), or quality of life between groups after long-term follow-up (median 65 months, range: 15-141). CONCLUSIONS: In this observational study, USCDT was associated with shortened treatment duration, shorter hospital stay, and less intravenous stenting, compared to CDT alone without affecting the long-term prevalence of PTS or quality of life. PMID- 27250357 TI - Diffusion-Weighted MRI Assessment of Adjacent Disc Degeneration After Thoracolumbar Vertebral Fractures. AB - OBJECTIVE: The purpose of this study was to assess, by the mean apparent diffusion coefficient (ADC), if a relationship exists between disc ADC and MR findings of adjacent disc degeneration after thoracolumbar fractures treated by anatomic reduction using vertebral augmentation (VAP). MATERIALS AND METHODS: Twenty non-consecutive patients (mean age 50.7 years; range 45-56) treated because of vertebral fractures, were included in this study. There were 10 A3.1 and 10 A1.2 fractures (AO classification). Surgical treatment using VAP was applied in 14 cases, and conservative in 6 patients. MRI T2-weighted images and mapping of apparent diffusion coefficient (ADC) of the intervertebral disc adjacent to the fractured segment were performed after a mean follow-up of 32 months. A total of 60 discs, 3 per patient, were analysed: infra-adjacent, supra adjacent and a control disc one level above the supra-adjacent. RESULTS: No differences between patients surgically treated and those following a conservative protocol regarding the average ADC values obtained in the 20 control discs analysed were found. Considering all discs, average ADC in the supra adjacent level was lower than in the infra-adjacent (1.35 +/- 0.12 vs. 1.53 +/- 0.06; p < 0.001). Average ADC values of the discs used as a control were similar to those of the infra-adjacent level (1.54 +/- 0.06). Compared to surgically treated patients, discs at the supra-adjacent fracture level showed statistically significant lower values in cases treated conservatively (p < 0.001). The variation in the delay of surgery had no influence on the average values of ADC at any of the measured levels. CONCLUSIONS: ADC measurements of the supra adjacent discs after a mean follow-up of 32 months following thoracolumbar fractures, showed that restoration of the vertebral collapse by minimally invasive VAP prevents posttraumatic disc degeneration. PMID- 27250359 TI - Partial oxidation of step-bound water leads to anomalous pH effects on metal electrode step-edges. AB - The design of better heterogeneous catalysts for applications such as fuel cells and electrolyzers requires a mechanistic understanding of electrocatalytic reactions and the dependence of their activity on operating conditions such as pH. A satisfactory explanation for the unexpected pH dependence of electrochemical properties of platinum surfaces has so far remained elusive, with previous explanations resorting to complex co-adsorption of multiple species and resulting in limited predictive power. This knowledge gap suggests that the fundamental properties of these catalysts are not yet understood, limiting systematic improvement. Here, we analyze the change in charge and free energies upon adsorption using density-functional theory (DFT) to establish that water adsorbs on platinum step edges across a wide voltage range, including the double layer region, with a loss of approximately 0.2 electrons upon adsorption. We show how this as-yet unreported change in net surface charge due to this water explains the anomalous pH variations of the hydrogen underpotential deposition (Hupd) and the potentials of zero total charge (PZTC) observed in published experimental data. This partial oxidation of water is not limited to platinum metal step edges, and we report the charge of the water on metal step edges of commonly used catalytic metals, including copper, silver, iridium, and palladium, illustrating that this partial oxidation of water broadly influences the reactivity of metal electrodes. PMID- 27250360 TI - Which way is which? Examining symbolic control of attention with compound arrow cues. AB - Spatial symbols can generate attentional biases toward peripheral locations compatible with the symbol's meaning. An important question concerns how one symbol is selected when competing symbols are present. Studies examining this issue for spatially distinct symbols have suggested that selection depends on the task goals. In the present study, we examined whether the influence of competing symbolic stimuli (arrows) at different levels of structure on attentional control also depends on the task goals. Participants made simple detection responses to a peripheral target preceded by a spatially uninformative compound arrow (global arrow composed of local arrows). In addition, participants were required to perform a secondary task in which they matched the orientation of the global arrow (global task) or the location of a uniquely colored local arrow (local task) to a test display presented immediately following a detection response. When the global and local arrows pointed at opposite locations, a local cueing effect emerged in the local task, and a global cueing effect in the global task, indicating that the task goals influenced the selection of the level of structure. However, when the local level was spatially neutral (global arrow, local rectangles), a cueing effect was observed independent of task, and when the global level was spatially neutral (global rectangle, local arrows), a cueing effect was observed in the local task only, suggesting that global processing was obligatory and local processing optional. These findings suggest that attentional effects triggered by the global level are more strongly reflexive than those triggered by the local level. PMID- 27250361 TI - Perceptual overloading reveals illusory contour perception without awareness of the inducers. AB - Unconscious perception is frequently examined by restricting visual input (e.g., using short stimulus durations followed by masking) to prevent that information from entering visual awareness. Failures to demonstrate perception without awareness may thus be a consequence of this restricted input rather than of limitations in unconscious perception. Here, we demonstrate a novel method that circumvents these significant drawbacks inherent in other methods. Using this new perceptual overloading technique (POT), in which stimuli are repeatedly presented in alternation with a stream of variable masks, we demonstrate illusory contour perception and modal completion even when subjects are completely unaware of the inducing elements. In addition to demonstrating a powerful new method to study consciousness by effectively gating robust visual input from visual awareness, we show that more complex contextual effects, previously considered to be a privilege only of conscious vision, can occur without awareness. PMID- 27250362 TI - Perceptual salience captures the eyes on a surprise trial. AB - A number of characteristics of the visual system and of the visual stimulus are invoked to explain involuntary control of attention, including goals, novelty, and perceptual salience. The present experiment tested perceptual salience on a surprise trial, that is, on its unannounced first presentation following trials lacking any salient items, thus eliminating possible confounds by current goals. Moreover, the salient item's location was not singled out by a novel feature, thus eliminating a possible confound by novelty in directing attention. Eye tracking was used to measure involuntary attention. Results show a prioritization of the salient item. However, contrary to predictions of prominent neuro computational and psychological salience models, prioritization was not fast acting. Rather the observers' gaze was attracted only as the second fixation on average or later (depending on condition) and with a latency of more than 500 ms on average. These results support the general proposition that salience can control attention. However, contrary to most salience models, the present results indicate that salience changes attentional priority only in novel environments. PMID- 27250363 TI - Identifying visual targets amongst interfering distractors: Sorting out the roles of perceptual load, dilution, and attentional zoom. AB - Visual selection is imperfect; whenever a complex array of objects is processed, representations of multiple objects are likely to be active simultaneously. A full account of attentional processing must explain how these representations affect one another and how they interact to produce a response. Evidence on these interactions comes from measures of distractor interference and from dilution of distractor effects by other nontargets. Based on these data, different principles have been proposed to help understand target-distractor interactions, including accounts based on perceptual load and on dilution among nontargets. We review evidence from a number of experiments, including some using Yantis and Jonides's (Journal of Experimental Psychology: Human Perception and Performance, 10, 601 621, 1984, Journal of Experimental Psychology: Human Perception and Performance, 16, 121-134, 1990) methods for preventing abrupt onsets, which can disrupt spatial attention. The results underscore spatial constraints on the allocation of attention to include targets and exclude distractors. Selection is most effective when a single region can be selected that includes all possible target locations and excludes possible distractor locations. This region can be expanded or contracted as needed for the task, as suggested by C. W. Eriksen and St. James's (Perception & Psychophysics, 40, 225-240, 1986) zoom lens model. This attentional zoom setting is probably affected by a number of factors, including the number of nontargets, the similarity among stimulus elements, the discriminability of the possible targets, and the discrimination difficulty of a concurrent task. A narrower attentional zoom setting that excludes a distractor will prevent interference from that distractor. Interference from a distractor will be diluted by nontargets, but only if they are within the attentional zoom region. PMID- 27250364 TI - High hydrostatic pressure adaptive strategies in an obligate piezophile Pyrococcus yayanosii. AB - Pyrococcus yayanosii CH1, as the first and only obligate piezophilic hyperthermophilic microorganism discovered to date, extends the physical and chemical limits of life on Earth. It was isolated from the Ashadze hydrothermal vent at 4,100 m depth. Multi-omics analyses were performed to study the mechanisms used by the cell to cope with high hydrostatic pressure variations. In silico analyses showed that the P. yayanosii genome is highly adapted to its harsh environment, with a loss of aromatic amino acid biosynthesis pathways and the high constitutive expression of the energy metabolism compared with other non obligate piezophilic Pyrococcus species. Differential proteomics and transcriptomics analyses identified key hydrostatic pressure-responsive genes involved in translation, chemotaxis, energy metabolism (hydrogenases and formate metabolism) and Clustered Regularly Interspaced Short Palindromic Repeats sequences associated with Cellular apoptosis susceptibility proteins. PMID- 27250366 TI - Invited Article: Quantitative imaging of explosions with high-speed cameras. AB - The techniques presented in this paper allow for mapping of temperature, pressure, chemical species, and energy deposition during and following detonations of explosives, using high speed cameras as the main diagnostic tool. This work provides measurement in the explosive near to far-field (0-500 charge diameters) of surface temperatures, peak air-shock pressures, some chemical species signatures, shock energy deposition, and air shock formation. PMID- 27250367 TI - Preface: The 5th International Workshop on X-ray Mirror Design, Fabrication, and Metrology. AB - Recent developments in synchrotron storage rings and free-electron laser-based x ray sources with ever-increasing brightness and coherent flux have pushed x-ray optics requirements to new frontiers. This Special Topic gathers a set of articles derived from a subset of the key presentations of the International Workshop on X-ray Mirrors Fabrication (IWXM-2015) and Metrology held at Lawrence Berkley National Laboratory, Berkeley, California, USA, July 14-16, 2015. The workshop objective was to report on recent progress in x-ray synchrotron radiation mirrors fabrication as well as on new developments in related metrology tools and methods. PMID- 27250368 TI - Damage threshold of coating materials on x-ray mirror for x-ray free electron laser. AB - We evaluated the damage threshold of coating materials such as Mo, Ru, Rh, W, and Pt on Si substrates, and that of uncoated Si substrate, for mirror optics of X ray free electron lasers (XFELs). Focused 1 MUm (full width at half maximum) XFEL pulses with the energies of 5.5 and 10 keV, generated by the SPring-8 angstrom compact free electron laser (SACLA), were irradiated under the grazing incidence condition. The damage thresholds were evaluated by in situ measurements of X-ray reflectivity degradation during irradiation by multiple pulses. The measured damage fluences below the critical angles were sufficiently high compared with the unfocused SACLA beam fluence. Rh coating was adopted for two mirror systems of SACLA. One system was a beamline transport mirror system that was partially coated with Rh for optional utilization of a pink beam in the photon energy range of more than 20 keV. The other was an improved version of the 1 MUm focusing mirror system, and no damage was observed after one year of operation. PMID- 27250365 TI - Current pharmacotherapy and putative disease-modifying therapy for Alzheimer's disease. AB - Alzheimer's disease (AD) is an age-related neurodegenerative disease of the central nervous system correlated with the progressive loss of cognition and memory. beta-Amyloid plaques, neurofibrillary tangles and the deficiency in cholinergic neurotransmission constitute the major hallmarks of the AD. Two major hypotheses have been implicated in the pathogenesis of AD namely the cholinergic hypothesis which ascribed the clinical features of dementia to the deficit cholinergic neurotransmission and the amyloid cascade hypothesis which emphasized on the deposition of insoluble peptides formed due to the faulty cleavage of the amyloid precursor protein. Current pharmacotherapy includes mainly the acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor agonist which offer symptomatic therapy and does not address the underlying cause of the disease. The disease-modifying therapy has garnered a lot of research interest for the development of effective pharmacotherapy for AD. beta and gamma-Secretase constitute attractive targets that are focussed in the disease-modifying approach. Potentiation of alpha-secretase also seems to be a promising approach towards the development of an effective anti-Alzheimer therapy. Additionally, the ameliorative agents that prevent aggregation of amyloid peptide and also the ones that modulate inflammation and oxidative damage associated with the disease are focussed upon. Development in the area of the vaccines is in progress to combat the characteristic hallmarks of the disease. Use of cholesterol-lowering agents also is a fruitful strategy for the alleviation of the disease as a close association between the cholesterol and AD has been cited. The present review underlines the major therapeutic strategies for AD with focus on the new developments that are on their way to amend the current therapeutic scenario of the disease. PMID- 27250369 TI - Development of a multi-lane X-ray mirror providing variable beam sizes. AB - Grazing incidence mirrors are used on most X-ray synchrotron beamlines to focus, collimate or suppress harmonics. Increasingly beamline users are demanding variable beam shapes and sizes at the sample position. We have now developed a new concept to rapidly vary the beam size and shape of a focused X-ray beam. The surface of an elliptically figured mirror is divided into a number of laterally separated lanes, each of which is given an additional longitudinal height profile calculated to shape the X-ray beam to a top-hat profile in the focal plane. We have now fabricated two prototype mirrors and present the results of metrology tests and measurements made with one of the mirrors focusing the X-rays on a synchrotron beamline. We envisage that such mirrors could be widely applied to rapid beam-size switching on many synchrotron beamlines. PMID- 27250370 TI - Development of high-order harmonic focusing system based on ellipsoidal mirror. AB - We have developed a focusing system for extreme ultraviolet light produced by high-order harmonic generation. An ellipsoidal mirror with a precise surface shape was fabricated and installed into the focusing system. A rigid mirror manipulator and a beam profiler were employed to perform precise and stable mirror alignment. As a demonstration of the focusing performance, high-order harmonics in the wavelength range of 13.5-19.5 nm were successfully focused into a 2.4 * 2.3 MUm(2) spot. PMID- 27250371 TI - Ultra-precision fabrication of 500 mm long and laterally graded Ru/C multilayer mirrors for X-ray light sources. AB - X-ray mirrors are needed for beam shaping and monochromatization at advanced research light sources, for instance, free-electron lasers and synchrotron sources. Such mirrors consist of a substrate and a coating. The shape accuracy of the substrate and the layer precision of the coating are the crucial parameters that determine the beam properties required for various applications. In principal, the selection of the layer materials determines the mirror reflectivity. A single layer mirror offers high reflectivity in the range of total external reflection, whereas the reflectivity is reduced considerably above the critical angle. A periodic multilayer can enhance the reflectivity at higher angles due to Bragg reflection. Here, the selection of a suitable combination of layer materials is essential to achieve a high flux at distinct photon energies, which is often required for applications such as microtomography, diffraction, or protein crystallography. This contribution presents the current development of a Ru/C multilayer mirror prepared by magnetron sputtering with a sputtering facility that was designed in-house at the Helmholtz-Zentrum Geesthacht. The deposition conditions were optimized in order to achieve ultra-high precision and high flux in future mirrors. Input for the improved deposition parameters came from investigations by transmission electron microscopy. The X-ray optical properties were investigated by means of X-ray reflectometry using Cu- and Mo radiation. The change of the multilayer d-spacing over the mirror dimensions and the variation of the Bragg angles were determined. The results demonstrate the ability to precisely control the variation in thickness over the whole mirror length of 500 mm thus achieving picometer-precision in the meter-range. PMID- 27250372 TI - Optimized mirror shape tuning using beam weightings based on distance, angle of incidence, reflectivity, and power. AB - For glancing-incidence optical systems, such as short-wavelength optics used for nano-focusing, incorporating physical factors in the calculations used for shape optimization can improve performance. Wavefront metrology, including the measurement of a mirror's shape or slope, is routinely used as input for mirror figure optimization on mirrors that can be bent, actuated, positioned, or aligned. Modeling shows that when the incident power distribution, distance from focus, angle of incidence, and the spatially varying reflectivity are included in the optimization, higher Strehl ratios can be achieved. Following the works of Marechal and Mahajan, optimization of the Strehl ratio (for peak intensity with a coherently illuminated system) occurs when the expectation value of the phase error's variance is minimized. We describe an optimization procedure based on regression analysis that incorporates these physical parameters. This approach is suitable for coherently illuminated systems of nearly diffraction-limited quality. Mathematically, this work is an enhancement of the methods commonly applied for ex situ alignment based on uniform weighting of all points on the surface (or a sub-region of the surface). It follows a similar approach to the optimization of apodized and non-uniformly illuminated optical systems. Significantly, it reaches a different conclusion than a more recent approach based on minimization of focal plane ray errors. PMID- 27250373 TI - Large aperture Fizeau interferometer commissioning and preliminary measurements of a long x-ray mirror at European X-ray Free Electron Laser. AB - The European XFEL (X-ray Free Electron Laser) is a large facility under construction in Hamburg, Germany. It will provide a transversally fully coherent x-ray radiation with outstanding characteristics: high repetition rate (up to 2700 pulses with a 0.6 ms long pulse train at 10 Hz), short wavelength (down to 0.05 nm), short pulse (in the femtoseconds scale), and high average brilliance (1.6 ? 10(25) (photons s(-1) mm(-2) mrad(-2))/0.1% bandwidth). The beam has very high pulse energy; therefore, it has to be spread out on a relatively long mirror (about 1 m). Due to the very short wavelength, the mirrors need to have a high quality surface on their entire length, and this is considered very challenging even with the most advanced polishing methods. In order to measure the mirrors and to characterize their interaction with the mechanical mount, we equipped a metrology laboratory with a large aperture Fizeau interferometer. The system is a classical 100 mm diameter commercial Fizeau, with an additional expander providing a 300 mm diameter beam. Despite the commercial nature of the system, special care has been taken in the polishing of the reference flats and in the expander quality. We report the first commissioning of the instrument, its calibration, and performance characterization, together with some preliminary results with the measurement of a 950 mm silicon substrate. The intended application is to characterize the final XFEL mirrors with nanometer accuracy. PMID- 27250374 TI - Nano-metrology: The art of measuring X-ray mirrors with slope errors <100 nrad. AB - We present a comprehensive investigation of the systematic and random errors of the nano-metrology instruments used to characterize synchrotron X-ray optics at Diamond Light Source. With experimental skill and careful analysis, we show that these instruments used in combination are capable of measuring state-of-the-art X ray mirrors. Examples are provided of how Diamond metrology data have helped to achieve slope errors of <100 nrad for optical systems installed on synchrotron beamlines, including: iterative correction of substrates using ion beam figuring and optimal clamping of monochromator grating blanks in their holders. Simulations demonstrate how random noise from the Diamond-NOM's autocollimator adds into the overall measured value of the mirror's slope error, and thus predict how many averaged scans are required to accurately characterize different grades of mirror. PMID- 27250375 TI - Application of advanced shearing techniques to the calibration of autocollimators with small angle generators and investigation of error sources. AB - The application of advanced error-separating shearing techniques to the precise calibration of autocollimators with Small Angle Generators (SAGs) was carried out for the first time. The experimental realization was achieved using the High Precision Small Angle Generator (HPSAG) of TUBITAK UME under classical dimensional metrology laboratory environmental conditions. The standard uncertainty value of 5 mas (24.2 nrad) reached by classical calibration method was improved to the level of 1.38 mas (6.7 nrad). Shearing techniques, which offer a unique opportunity to separate the errors of devices without recourse to any external standard, were first adapted by Physikalisch-Technische Bundesanstalt (PTB) to the calibration of autocollimators with angle encoders. It has been demonstrated experimentally in a clean room environment using the primary angle standard of PTB (WMT 220). The application of the technique to a different type of angle measurement system extends the range of the shearing technique further and reveals other advantages. For example, the angular scales of the SAGs are based on linear measurement systems (e.g., capacitive nanosensors for the HPSAG). Therefore, SAGs show different systematic errors when compared to angle encoders. In addition to the error-separation of HPSAG and the autocollimator, detailed investigations on error sources were carried out. Apart from determination of the systematic errors of the capacitive sensor used in the HPSAG, it was also demonstrated that the shearing method enables the unique opportunity to characterize other error sources such as errors due to temperature drift in long term measurements. This proves that the shearing technique is a very powerful method for investigating angle measuring systems, for their improvement, and for specifying precautions to be taken during the measurements. PMID- 27250376 TI - High precision tilt stage as a key element to a universal test mirror for characterization and calibration of slope measuring instruments. AB - The ultimate performance of surface slope metrology instrumentation, such as long trace profilers and auto-collimator based deflectometers, is limited by systematic errors that are increased when the entire angular range is used for metrology of significantly curved optics. At the ALS X-Ray Optics Laboratory, in collaboration with the HZB/BESSY-II and PTB (Germany) metrology teams, we are working on a calibration method for deflectometers, based on a concept of a universal test mirror (UTM) [V. V. Yashchuk et al., Proc. SPIE 6704, 67040A (2007)]. Potentially, the UTM method provides high performance calibration and accounts for peculiarities of the optics under test (e.g., slope distribution) and the experimental arrangement (e.g., the distance between the sensor and the optic under test). At the same time, the UTM calibration method is inherently universal, applicable to a variety of optics and experimental arrangements. In this work, we present the results of tests with a key component of the UTM system, a custom high precision tilt stage, which has been recently developed in collaboration with Physik Instrumente, GmbH. The tests have demonstrated high performance of the stage and its capability (after additional calibration) to provide angular calibration of surface slope measuring profilers over the entire instrumental dynamic range with absolute accuracy better than 30 nrad. The details of the stage design and tests are presented. We also discuss the foundation of the UTM method and calibration algorithm, as well as the possible design of a full scale UTM system. PMID- 27250377 TI - Stitching interferometry for ellipsoidal x-ray mirrors. AB - Ellipsoidal mirrors, which can efficiently produce a two-dimensional focusing beam with a single mirror, are superior x-ray focusing optics, especially when compared to elliptical-cylinder mirrors in the Kirkpatrick-Baez geometry. However, nano-focusing ellipsoidal mirrors are not commonly used for x-ray optics because achieving the accuracy required for the surface metrology of nano focusing ellipsoidal mirrors is difficult due to their small radius of curvature along the short ellipsoidal axis. Here, we developed a surface metrology system for nano-focusing ellipsoidal mirrors using stitching interferometric techniques. The developed system simultaneously measures sub-aperture shapes with a microscopic interferometer and the tilt angles of the sub-aperture shapes with a large Fizeau interferometer. After correcting the systematic errors included in the sub-aperture shapes, the entire mirror shape is calculated by stitching the sub-aperture shapes based on the obtained relative angles between partially overlapped sub-apertures. In this study, we developed correction methods for systematic errors in sub-aperture shapes that originated from off-axis aberrations produced in the optics of the microscopic interferometer. The systematic errors on an ellipsoidal mirror were estimated by measuring a series of tilted plane substrates and the ellipsoidal substrate. From measurements of an ellipsoidal mirror with a 3.6-mm radius of curvature at the mirror center, we obtained a measurement repeatability of 0.51 nm (root-mean-square) in an assessment area of 0.5 mm * 99.18 mm. This value satisfies the requirements for surface metrology of nano-focusing x-ray mirrors. Thus, the developed metrology system should be applicable for fabricating nano-focusing ellipsoidal mirrors. PMID- 27250378 TI - Aperture alignment in autocollimator-based deflectometric profilometers. AB - During the last ten years, deflectometric profilometers have become indispensable tools for the precision form measurement of optical surfaces. They have proven to be especially suitable for characterizing beam-shaping optical surfaces for x-ray beamline applications at synchrotrons and free electron lasers. Deflectometric profilometers use surface slope (angle) to assess topography and utilize commercial autocollimators for the contactless slope measurement. To this purpose, the autocollimator beam is deflected by a movable optical square (or pentaprism) towards the surface where a co-moving aperture limits and defines the beam footprint. In this paper, we focus on the precise and reproducible alignment of the aperture relative to the autocollimator's optical axis. Its alignment needs to be maintained while it is scanned across the surface under test. The reproducibility of the autocollimator's measuring conditions during calibration and during its use in the profilometer is of crucial importance to providing precise and traceable angle metrology. In the first part of the paper, we present the aperture alignment procedure developed at the Advanced Light Source, Lawrence Berkeley National Laboratory, USA, for the use of their deflectometric profilometers. In the second part, we investigate the topic further by providing extensive ray tracing simulations and calibrations of a commercial autocollimator performed at the Physikalisch-Technische Bundesanstalt, Germany, for evaluating the effects of the positioning of the aperture on the autocollimator's angle response. The investigations which we performed are crucial for reaching fundamental metrological limits in deflectometric profilometry. PMID- 27250379 TI - Linear chirped slope profile for spatial calibration in slope measuring deflectometry. AB - Slope measuring deflectometry is commonly used by the X-ray optics community to measure the long-spatial-wavelength surface figure error of optical components dedicated to guide and focus X-rays under grazing incidence condition at synchrotron and free electron laser beamlines. The best performing instruments of this kind are capable of absolute accuracy on the level of 30-50 nrad. However, the exact bandwidth of the measurements, determined at the higher spatial frequencies by the instrument's spatial resolution, or more generally by the instrument's modulation transfer function (MTF) is hard to determine. An MTF calibration method based on application of a test surface with a one-dimensional (1D) chirped height profile of constant amplitude was suggested in the past. In this work, we propose a new approach to designing the test surfaces with a 2D chirped topography, specially optimized for MTF characterization of slope measuring instruments. The design of the developed MTF test samples based on the proposed linear chirped slope profiles (LCSPs) is free of the major drawback of the 1D chirped height profiles, where in the slope domain, the amplitude strongly increases with the local spatial frequency of the profile. We provide the details of fabrication of the LCSP samples. The results of first application of the developed test samples to measure the spatial resolution of the BESSY-NOM at different experimental arrangements are also presented and discussed. PMID- 27250380 TI - Stitching methods at the European Synchrotron Radiation Facility (ESRF). AB - X-ray mirror quality has continuously improved over the past 20 years and manufacturers are now able to provide long mirrors with slope errors below 0.2 MUrad. Nevertheless, these mirrors are mounted on holders or even mechanical benders to adjust their curvature and their intrinsic quality must be preserved from any parasitic deformation such as twist. The most direct method of detecting these deformations is to measure the 3D topography of the optical surface. At the ESRF metrology laboratory, three different stitching systems are under development based on Fizeau sub-aperture measurements. The first one consists of measuring long flat mirrors, the second based on the relative angle determinable stitching interferometry (RADSI) method developed at SPring-8 is aimed primarily at the measurement of short mirrors with strong curvature down to a few meters, and the last, also based on the RADSI method, is dedicated to characterize longer mirrors with intermediate curvature. For each method we will describe the measurement setup and discuss first results obtained. Micro-stitching interferometry is also currently used at the ESRF metrology laboratory. The technique is suitable for measuring deeply curved aspherical profiles and will be illustrated with results from a Kirkpatrick-Baez mirror system for nano-focusing. PMID- 27250381 TI - Speckle-based at-wavelength metrology of X-ray mirrors with super accuracy. AB - X-ray active mirrors, such as bimorph and mechanically bendable mirrors, are increasingly being used on beamlines at modern synchrotron source facilities to generate either focused or "tophat" beams. As well as optical tests in the metrology lab, it is becoming increasingly important to optimise and characterise active optics under actual beamline operating conditions. Recently developed X ray speckle-based at-wavelength metrology technique has shown great potential. The technique has been established and further developed at the Diamond Light Source and is increasingly being used to optimise active mirrors. Details of the X-ray speckle-based at-wavelength metrology technique and an example of its applicability in characterising and optimising a micro-focusing bimorph X-ray mirror are presented. Importantly, an unprecedented angular sensitivity in the range of two nanoradians for measuring the slope error of an optical surface has been demonstrated. Such a super precision metrology technique will be beneficial to the manufacturers of polished mirrors and also in optimization of beam shaping during experiments. PMID- 27250382 TI - Optical pseudomotors for soft x-ray beamlines. AB - Optical elements of soft x-ray beamlines usually have motorized translations and rotations that allow for the fine alignment of the beamline. This is to steer the photon beam at some positions and to correct the focus on slits or on sample. Generally, each degree of freedom of a mirror induces a change of several parameters of the beam. Inversely, several motions are required to actuate on a single optical parameter, keeping the others unchanged. We define optical pseudomotors as combinations of physical motions of the optical elements of a beamline, which allow modifying one optical parameter without affecting the others. We describe a method to obtain analytic relationships between physical motions of mirrors and the corresponding variations of the beam parameters. This method has been implemented and tested at two beamlines at ALBA, where it is used to control the focus of the photon beam and its position independently. PMID- 27250383 TI - X-ray metrology and performance of a 45-cm long x-ray deformable mirror. AB - We describe experiments with a 45-cm long x-ray deformable mirror (XDM) that have been conducted in End Station 2, Beamline 5.3.1 at the Advanced Light Source. A detailed description of the hardware implementation is provided. We explain our one-dimensional Fresnel propagation code that correctly handles grazing incidence and includes a model of the XDM. This code is used to simulate and verify experimental results. Initial long trace profiler metrology of the XDM at 7.5 keV is presented. The ability to measure a large (150-nm amplitude) height change on the XDM is demonstrated. The results agree well with the simulated experiment at an error level of 1 MUrad RMS. Direct imaging of the x-ray beam also shows the expected change in intensity profile at the detector. PMID- 27250384 TI - Development and implementation of a portable grating interferometer system as a standard tool for testing optics at the Advanced Photon Source beamline 1-BM. AB - We developed a portable X-ray grating interferometer setup as a standard tool for testing optics at the Advanced Photon Source (APS) beamline 1-BM. The interferometer can be operated in phase-stepping, Moire, or single-grating harmonic imaging mode with 1-D or 2-D gratings. All of the interferometer motions are motorized; hence, it is much easier and quicker to switch between the different modes of operation. A novel aspect of this new instrument is its designed portability. While the setup is designed to be primarily used as a standard tool for testing optics at 1-BM, it could be potentially deployed at other APS beamlines for beam coherence and wavefront characterization or imaging. The design of the interferometer system is described in detail and coherence measurements obtained at the APS 34-ID-E beamline are presented. The coherence was probed in two directions using a 2-D checkerboard, a linear, and a circular grating at X-ray energies of 8 keV, 11 keV, and 18 keV. PMID- 27250386 TI - Tunable hard X-ray spectrometer utilizing asymmetric planes of a quartz transmission crystal. AB - A Cauchois type hard x-ray spectrometer was developed that utilizes the (301) diffraction planes at an asymmetric angle of 23.51 degrees to the normal to the surface of a cylindrically curved quartz transmission crystal. The energy coverage is tunable by rotating the crystal and the detector arm, and spectra were recorded in the 8 keV to 20 keV range with greater than 2000 resolving power. The high resolution results from low aberrations enabled by the nearly perpendicular angle of the diffracted rays with the back surface of the crystal. By using other asymmetric planes of the same crystal and rotating to selected angles, the spectrometer can operate with high resolution up to 50 keV. PMID- 27250385 TI - At-wavelength metrology facility for soft X-ray reflection optics. AB - A new Optics Beamline coupled to a versatile UHV reflectometer is successfully operating at BESSY-II. It is used to carry out at-wavelength characterization and calibration of in-house produced gratings and novel nano-optical devices as well as mirrors and multilayer systems in the UV and XUV spectral region. This paper presents most recent commissioning data of the beamline and shows their correlation with initial beamline design calculations. Special attention is paid to beamline key parameters which determine the quality of the measurements such as high-order suppression and stray light behavior. The facility is open to user operation. PMID- 27250387 TI - A mobile system for a comprehensive online-characterization of nanoparticle aggregates based on wide-angle light scattering and laser-induced incandescence. AB - A mobile demonstrator for the comprehensive online-characterization of gas-borne nanoparticle aggregates is presented. Two optical measurement techniques are combined, both utilizing a pulsed Nd:YAG laser as light source. Aggregate size and fractal dimension are measured by Wide-Angle Light Scattering (WALS). An ellipsoidal mirror images elastically scattered light from scattering angles between 10 degrees and 165 degrees onto a CCD-camera chip resulting in an almost complete scattering diagram with high angular resolution. Primary particle size and volume fraction are measured by time-resolved Laser-Induced Incandescence (TiRe-LII). Here, particles are heated up to about 3000 K by the short laser pulse, the enhanced thermal radiation signal is detected with gated photomultiplier tubes. Analysis of the signal decay time and maximum LII-signal allows for the determination of primary particle diameter and volume fraction. The performance of the system is demonstrated by combined measurements on soot nanoparticle aggregates from a soot aerosol generator. Particle and aggregate sizes are varied by using different equivalence ratios of the combustion in the generator. Soot volume fraction can be adjusted by different levels of dilution with air. Online-measurements were carried out demonstrating the favorable performance of the system and the potential for industrial applications such as process control and product development. The particle properties obtained are confirmed through transmission electron microscopy analysis on representative samples. PMID- 27250388 TI - A cylindrical quadrupole ion trap in combination with an electrospray ion source for gas-phase luminescence and absorption spectroscopy. AB - A relatively simple setup for collection and detection of light emitted from isolated photo-excited molecular ions has been constructed. It benefits from a high collection efficiency of photons, which is accomplished by using a cylindrical ion trap where one end-cap electrode is a mesh grid combined with an aspheric condenser lens. The geometry permits nearly 10% of the emitted light to be collected and, after transmission losses, approximately 5% to be delivered to the entrance of a grating spectrometer equipped with a detector array. The high collection efficiency enables the use of pulsed tunable lasers with low repetition rates (e.g., 20 Hz) instead of continuous wave (cw) lasers or very high repetition rate (e.g., MHz) lasers that are typically used as light sources for gas-phase fluorescence experiments on molecular ions. A hole has been drilled in the cylinder electrode so that a light pulse can interact with the ion cloud in the center of the trap. Simulations indicate that these modifications to the trap do not significantly affect the storage capability and the overall shape of the ion cloud. The overlap between the ion cloud and the laser light is basically 100%, and experimentally >50% of negatively charged chromophore ions are routinely photodepleted. The performance of the setup is illustrated based on fluorescence spectra of several laser dyes, and the quality of these spectra is comparable to those reported by other groups. Finally, by replacing the optical system with a channeltron detector, we demonstrate that the setup can also be used for gas-phase action spectroscopy where either depletion or fragmentation is monitored to provide an indirect measurement on the absorption spectrum of the ion. PMID- 27250389 TI - A highly versatile optical fibre vacuum feed-through. AB - Coupling light into a vacuum system is a non-trivial problem, requiring the use of a specialized feed-through. This feed-through must be both leak tight and offer a low optical loss if it is to be suitable for general use. In this paper, we report on the development of an extremely simple yet versatile, low cost, demountable optical fiber vacuum feed-through based on the modification of a standard optical fiber bulkhead connector. The modified connector was found to have a leak rate of 6.6 +/- 2.1 * 10(-6) mbar l/s and an optical loss of -0.41 +/ 0.28 dB, making it suitable for use in high vacuum applications. PMID- 27250390 TI - Injection locking of a low cost high power laser diode at 461 nm. AB - Stable laser sources at 461 nm are important for optical cooling of strontium atoms. In most existing experiments, this wavelength is obtained by frequency doubling infrared lasers, since blue laser diodes either have low power or large emission bandwidths. Here, we show that injecting less than 10 mW of monomode laser radiation into a blue multimode 500 mW high power laser diode is capable of slaving at least 50% of the power to the desired frequency. We verify the emission bandwidth reduction by saturation spectroscopy on a strontium gas cell and by direct beating of the slave with the master laser. We also demonstrate that the laser can efficiently be used within the Zeeman slower for optical cooling of a strontium atomic beam. PMID- 27250391 TI - Grazing incidence off Rowland spectrometer with shifted slit. AB - The article presents the analysis of the scheme of grazing incidence spectrometer with the normal to the line of site registration of the spectrum. The scheme is intended for the usage of the micro channel plate assembly as a spectrum detector. The main feature is the displacement of the entrance slit from the Rowland circle. The results of the experimental test of the spectral resolution (lambda/deltalambda around 200) are presented and compared with the theoretical estimations. PMID- 27250392 TI - Characteristics and performance of offset phase locked single frequency heterodyned laser systems. AB - We demonstrate and characterize the performance of two heterodyned optical phase locked loop (PLL) laser systems for use in characterizing photodetector RF frequency response and nonlinearities. Descriptions of PLL circuit parameters for Nd:YAG non-planar ring oscillator lasers at 1064 nm and 1319 nm, and Er ion fiber lasers from 1530 nm to 1565 nm are presented. Both laser systems have piezoelectric transducer wavelength control over the PLL voltage controlled oscillator circuit. Offset frequency phase locking from 1.5 kHz to 51+ GHz is demonstrated. Frequency stability at 10 MHz is measured to be +/-50 MUHz, limited by the stability of the Rb stabilized crystal oscillator. Phase noise of the phase-locked 1319 nm laser system is discussed where we find that the phase noise is dominated by the input source noise at frequency offsets below 100 Hz and by the laser's RIN noise at frequency offsets > 100 Hz. Comparing nonlinearity data from an InGaAs p-i-n photodiode using both 1319 nm and 1550 nm PLL nonlinearity measurement systems, we find two new separate photodetector nonlinearity mechanisms. Measurements of the harmonic components of a 11 MHz sinusoidal heterodyned optical beat note signal are found to be at or below 1 nW/mW for the second harmonic (at 22 MHz) and at or below 0.25 nW/mW for the 3rd harmonic (at 33 MHz), confirming the nearly pure sinusoidal nature of the optically generated microwave beat note. PMID- 27250393 TI - An improved hydrothermal diamond anvil cell. AB - A new type of HDAC-V hydrothermal diamond anvil cell (HDAC-VT) has been designed to meet the demands of X-ray research including X-Ray Fluorescence, X-ray Absorption Spectroscopy, and small angle X-ray scattering. The earlier version of HDAC-V that offered a large rectangular solid angle used two posts and two driver screws on both sides of a rectangular body. The new version HDAC-VT in a triangular shape has two alternative guide systems, either three posts inserted into bushings suitable for small anvil faces or linear ball bearings suitable for large anvil faces. The HDAC-VT having three driver screws offers the advantage of greater control and stability even though it sacrifices some of the size of solid angle. The greater control allows better sealing of samples, while greater stability results in longer survival for anvils and ceramic parts. This improved design retains several beneficial features of the original HDAC-V as well. These include the small collar that surrounds the heater and sample chamber forming an Ar + H2 gas chamber to protect diamonds and their heating parts from being oxidized. Three linear ball bearings, when used, fit to the three posts prevent seizing that can result from deterioration of lubricant at high temperatures. Positioning the posts and bearings outside of the gas chamber as in HDAC-V also prevents seizing and possible deformation due to overheating. In order to control the heating rate precisely with computer software, we use Linkam T95 and have replaced the Linkam 1400XY heating stage with the HDAC-VT allowing the HDAC to be heated to 950 degrees C at a rate from 0.01 degrees C/min to 50 degrees C/min. We have used the HDAC-VT and Linkam T95 to observe in situ nucleation and growth of zabuyelite in aqueous fluid and to homogenize melt inclusions in quartz from three porphyry deposits in Shanxi, China. PMID- 27250394 TI - TAKASAGO-6 apparatus for cryogenic coherent X-ray diffraction imaging of biological non-crystalline particles using X-ray free electron laser at SACLA. AB - Coherent X-ray diffraction imaging (CXDI) is a technique for structure analyses of non-crystalline particles with dimensions ranging from micrometer to sub micrometer. We have developed a diffraction apparatus named TAKASAGO-6 for use in single-shot CXDI experiments of frozen-hydrated non-crystalline biological particles at cryogenic temperature with X-ray free electron laser pulses provided at a repetition rate of 30 Hz from the SPring-8 Angstrom Compact free-electron LAser. Specimen particles are flash-cooled after being dispersed on thin membranes supported by specially designed disks. The apparatus is equipped with a high-speed translation stage with a cryogenic pot for raster-scanning of the disks at a speed higher than 25 MUm/33 ms. In addition, we use devices assisting the easy transfer of cooled specimens from liquid-nitrogen storages to the cryogenic pot. In the current experimental procedure, more than 20 000 diffraction patterns can be collected within 1 h. Here we report the key components and performance of the diffraction apparatus. Based on the efficiency of the diffraction data collection and the structure analyses of metal particles, biological cells, and cellular organelles, we discuss the future application of this diffraction apparatus for structure analyses of biological specimens. PMID- 27250395 TI - Active stabilization of ion trap radiofrequency potentials. AB - We actively stabilize the harmonic oscillation frequency of a laser-cooled atomic ion confined in a radiofrequency (rf) Paul trap by sampling and rectifying the high voltage rf applied to the trap electrodes. We are able to stabilize the 1 MHz atomic oscillation frequency to be better than 10 Hz or 10 ppm. This represents a suppression of ambient noise on the rf circuit by 34 dB. This technique could impact the sensitivity of ion trap mass spectrometry and the fidelity of quantum operations in ion trap quantum information applications. PMID- 27250396 TI - High-resolution three-dimensional spin- and angle-resolved photoelectron spectrometer using vacuum ultraviolet laser light. AB - We describe a spin- and angle-resolved photoelectron spectroscopy (SARPES) apparatus with a vacuum-ultraviolet (VUV) laser (hnu = 6.994 eV) developed at the Laser and Synchrotron Research Center at the Institute for Solid State Physics, The University of Tokyo. The spectrometer consists of a hemispherical photoelectron analyzer equipped with an electron deflector function and twin very low-energy-electron-diffraction-type spin detectors, which allows us to analyze the spin vector of a photoelectron three-dimensionally with both high energy and angular resolutions. The combination of the high-performance spectrometer and the high-photon-flux VUV laser can achieve an energy resolution of 1.7 meV for SARPES. We demonstrate that the present laser-SARPES machine realizes a quick SARPES on the spin-split band structure of a Bi(111) film even with 7 meV energy and 0.7(?) angular resolutions along the entrance-slit direction. This laser SARPES machine is applicable to the investigation of spin-dependent electronic states on an energy scale of a few meV. PMID- 27250397 TI - A highly miniaturized vacuum package for a trapped ion atomic clock. AB - We report on the development of a highly miniaturized vacuum package for use in an atomic clock utilizing trapped ytterbium-171 ions. The vacuum package is approximately 1 cm(3) in size and contains a linear quadrupole RF Paul ion trap, miniature neutral Yb sources, and a non-evaporable getter pump. We describe the fabrication process for making the Yb sources and assembling the vacuum package. To prepare the vacuum package for ion trapping, it was evacuated, baked at a high temperature, and then back filled with a helium buffer gas. Once appropriate vacuum conditions were achieved in the package, it was sealed with a copper pinch off and was subsequently pumped only by the non-evaporable getter. We demonstrated ion trapping in this vacuum package and the operation of an atomic clock, stabilizing a local oscillator to the 12.6 GHz hyperfine transition of (171)Y b(+). The fractional frequency stability of the clock was measured to be 2 * 10(-11)/tau(1/2). PMID- 27250398 TI - Comparison measurements of low-pressure between a laser refractometer and ultrasonic manometer. AB - We have developed a new low-pressure sensor which is based on the measurement of (nitrogen) gas refractivity inside a Fabry-Perot cavity. We compare pressure determinations via this laser refractometer to that of well-established ultrasonic manometers throughout the range 100 Pa to 180 000 Pa. The refractometer demonstrates 10(-6) ? p reproducibility for p > 100 Pa, and this precision outperforms a manometer. We also claim the refractometer has an expanded uncertainty of U(pFP) = [(2.0 mPa)(2) + (8.8 * 10(-6) ? p)(2)](1/2), as realized through the properties of nitrogen gas; we argue that a transfer of the pascal to p < 1 kPa using a laser refractometer is more accurate than the current primary realization. PMID- 27250399 TI - A microchip laser source with stable intensity and frequency used for self-mixing interferometry. AB - We present a stable 40 * 40 * 30 mm(3) Laser-diode (LD)-pumped-microchip laser (ML) laser source used for self-mixing interferometry which can measure non cooperative targets. We simplify the coupling process of pump light in order to make its polarization and intensity robust against environmental disturbance. Thermal frequency stabilization technology is used to stabilize the laser frequency of both LD and ML. Frequency stability of about 1 * 10(-7) and short term intensity fluctuation of 0.1% are achieved. The theoretical long-term displacement accuracy limited by frequency and intensity fluctuation is about 10 nm when the measuring range is 0.1 m. The line-width of this laser is about 25 kHz corresponding to 12 km coherent length and 6 km measurement range for self mixing interference. The laser source has been equipped to a self-mixing interferometer, and it works very well. PMID- 27250400 TI - Femtosecond broadband fluorescence upconversion spectroscopy: Spectral coverage versus efficiency. AB - Sum frequency mixing of fluorescence and ~1300 nm gate pulses, in a thin beta barium borate crystal and non-collinear type II geometry, is quantified as part of a femtosecond fluorimeter [X.-X. Zhang et al., Rev. Sci. Instrum. 82, 063108 (2011)]. For a series of fixed phasematching angles, the upconversion efficiency is measured depending on fluorescence wavelength. Two useful orientations of the crystal are related by rotation around the surface normal. Orientation A has higher efficiency (factor ~3) compared to B at the cost of some loss of spectral coverage for a given crystal angle. It should be used when subtle changes of an otherwise stationary emission band are to be monitored. With orientation B, the fluorescence range lambdaF > 420-750 nm is covered with a single setting of the crystal and less gate scatter around time zero. The accuracy of determining an instantaneous emission band shape is demonstrated by comparing results from two laboratories. PMID- 27250401 TI - Time-resolved pump and probe x-ray absorption fine structure spectroscopy at beamline P11 at PETRA III. AB - We report about the development and implementation of a new setup for time resolved X-ray absorption fine structure spectroscopy at beamline P11 utilizing the outstanding source properties of the low-emittance PETRA III synchrotron storage ring in Hamburg. Using a high intensity micrometer-sized X-ray beam in combination with two positional feedback systems, measurements were performed on the transition metal complex fac-Tris[2-phenylpyridinato-C2,N]iridium(III) also referred to as fac-Ir(ppy)3. This compound is a representative of the phosphorescent iridium(III) complexes, which play an important role in organic light emitting diode (OLED) technology. The experiment could directly prove the anticipated photoinduced charge transfer reaction. Our results further reveal that the temporal resolution of the experiment is limited by the PETRA III X-ray bunch length of ~103 ps full width at half maximum (FWHM). PMID- 27250402 TI - Ultrafast time measurements by time-correlated single photon counting coupled with superconducting single photon detector. AB - Time resolution is one of the main characteristics of the single photon detectors besides quantum efficiency and dark count rate. We demonstrate here an ultrafast time-correlated single photon counting (TCSPC) setup consisting of a newly developed single photon counting board SPC-150NX and a superconducting NbN single photon detector with a sensitive area of 7 * 7 MUm. The combination delivers a record instrument response function with a full width at half maximum of 17.8 ps and system quantum efficiency ~15% at wavelength of 1560 nm. A calculation of the root mean square value of the timing jitter for channels with counts more than 1% of the peak value yielded about 7.6 ps. The setup has also good timing stability of the detector-TCSPC board. PMID- 27250403 TI - Room temperature optically detected magnetic resonance (photoluminescence detected magnetic resonance) of radical ion pairs induced by vacuum ultraviolet in thin polymeric films. AB - A setup for recording optically detected electron paramagnetic resonance spectra of radical ions involved in geminate recombination and generated by vacuum ultraviolet is described. The setup allows registration of EPR spectra from short lived radical ions in polymeric films at room temperature by recombination fluorescence modulated by a resonance microwave field. PMID- 27250404 TI - In-vacuum scattered light reduction with black cupric oxide surfaces for sensitive fluorescence detection. AB - We demonstrate a simple and easy method for producing low-reflectivity surfaces that are ultra-high vacuum compatible, may be baked to high temperatures, and are easily applied even on complex surface geometries. Black cupric oxide (CuO) surfaces are chemically grown in minutes on any copper surface, allowing for low cost, rapid prototyping, and production. The reflective properties are measured to be comparable to commercially available products for creating optically black surfaces. We describe a vacuum apparatus which uses multiple blackened copper surfaces for sensitive, low-background detection of molecules using laser-induced fluorescence. PMID- 27250405 TI - A compact high-resolution X-ray ion mobility spectrometer. AB - For the ionization of gaseous samples, most ion mobility spectrometers employ radioactive ionization sources, e.g., containing (63)Ni or (3)H. Besides legal restrictions, radioactive materials have the disadvantage of a constant radiation with predetermined intensity. In this work, we replaced the (3)H source of our previously described high-resolution ion mobility spectrometer with 75 mm drift tube length with a commercially available X-ray source. It is shown that the current configuration maintains the resolving power of R = 100 which was reported for the original setup containing a (3)H source. The main advantage of an X-ray source is that the intensity of the radiation can be adjusted by varying its operating parameters, i.e., filament current and acceleration voltage. At the expense of reduced resolving power, the sensitivity of the setup can be increased by increasing the activity of the source. Therefore, the performance of the setup can be adjusted to the specific requirements of any application. To investigate the relation between operating parameters of the X-Ray source and the performance of the ion mobility spectrometer, parametric studies of filament current and acceleration voltage are performed and the influence on resolving power, peak height, and noise is analyzed. PMID- 27250406 TI - Atmospheric pressure X-ray photoelectron spectroscopy apparatus: Bridging the pressure gap. AB - One of the main goals in catalysis is the characterization of solid/gas interfaces in a reaction environment. The electronic structure and chemical composition of surfaces become heavily influenced by the surrounding environment. However, the lack of surface sensitive techniques that are able to monitor these modifications under high pressure conditions hinders the understanding of such processes. This limitation is known throughout the community as the "pressure gap." We have developed a novel experimental setup that provides chemical information on a molecular level under atmospheric pressure and in presence of reactive gases and at elevated temperatures. This approach is based on separating the vacuum environment from the high-pressure environment by a silicon nitride grid-that contains an array of micrometer-sized holes-coated with a bilayer of graphene. Using this configuration, we have investigated the local electronic structure of catalysts by means of photoelectron spectroscopy and in presence of gases at 1 atm. The reaction products were monitored online by mass spectrometry and gas chromatography. The successful operation of this setup was demonstrated with three different examples: the oxidation/reduction reaction of iridium (noble metal) and copper (transition metal) nanoparticles and with the hydrogenation of propyne on Pd black catalyst (powder). PMID- 27250407 TI - Ultralow-frequency Raman system down to 10 cm(-1) with longpass edge filters and its application to the interface coupling in t(2+2)LGs. AB - Ultralow-frequency (ULF) Raman spectroscopy becomes increasingly important in the area of two-dimensional (2D) layered materials; however, such measurement usually requires expensive and nonstandard equipment. Here, the measurement of ULF Raman signal down to 10 cm(-1) has been realized with high throughput by combining a kind of longpass edge filters with a single monochromator, which are verified by the Raman spectrum of L-cystine using three laser excitations. Fine adjustment of the angle of incident laser beam from normal of the longpass edge filters and selection of polarization geometry are demonstrated how to probe ULF Raman signal with high signal-to-noise. Davydov splitting of the shear mode in twisted (2+2) layer graphenes (t(2+2)LG) has been observed by such system in both exfoliated and transferred samples. We provide a direct evidence of twist-angle dependent softening of the shear coupling in t(2+2)LG, while the layer-breathing coupling at twisted interfaces is found to be almost identical to that in bulk graphite. This suggests that the exfoliation and transferring techniques are enough good to make a good 2D heterostructures to demonstrate potential device application. This Raman system will be potentially applied to the research field of ULF Raman spectroscopy. PMID- 27250408 TI - A simple counter-flow cooling system for a supersonic free-jet beam source assembly. AB - A simple design for an inexpensive, cooled, free-jet beam source is described. The source assembly features an integrated cooling system as supplied by a counter-flow of chilled nitrogen, and is composed primarily of off-the-shelf tube fittings. The design facilitates rapid implementation and eases subsequent alignment with respect to any downstream beamline aperture. The source assembly outlined cools the full length of the stagnation volume, offering temperature control down to 100 K and long-term temperature stability better than +/-1 K. PMID- 27250409 TI - A cylindrically symmetric "micro-Mott" electron polarimeter. AB - A small, novel, cylindrically symmetric Mott electron polarimeter is described. The effective Sherman function, Seff, or analyzing power, for 20 kV Au target bias with a 1.3 keV energy loss window is 0.16 +/- 0.01, where uncertainty in the measurement is due primarily to uncertainty in the incident electron polarization. For an energy loss window of 0.5 keV, Seff reaches its maximum value of 0.24 +/- 0.02. The device's maximum efficiency, I/Io, defined as the detected count rate divided by the incident particle rate, is 3.7 +/- 0.2 * 10( 4) at 20 keV. The figure-of-merit of the device, eta, is defined as Seff (2)IIo and equals 9.0 +/- 1.6 * 10(-6). Potential sources of false asymmetries due to detector electronic asymmetry and beam misalignment have been investigated. The new polarimeter's performance is compared to published results for similar compact retarding-field Mott polarimeters, and it is concluded that this device has a relatively large Seff and low efficiency. SIMION((r)) electron trajectory simulations and Sherman function calculations are presented to explain the differences in performance between this device and previous designs. This design has an Seff that is insensitive to spatial beam fluctuations and, for an energy loss window >0.5 keV, negligible background due to spurious ion and X-ray production at the target. PMID- 27250410 TI - Performance improvements of wavelength-shifting-fiber neutron detectors using high-resolution positioning algorithms. AB - Three high-resolution positioning methods based on the FluoroBancroft linear algebraic method [S. B. Andersson, Opt. Express 16, 18714 (2008)] are proposed for wavelength-shifting fiber (WLSF) neutron detectors. Using a Gaussian or exponential-decay light-response function, the non-linear relation of photon number profiles vs. x-pixels was linearized and neutron positions were determined. After taking the super-Poissonian photon noise into account, the proposed algorithms give an average of 0.03-0.08 pixel position error much smaller than that (0.29 pixel) from a traditional maximum photon algorithm (MPA). The new algorithms result in better detector uniformity, less position misassignment (ghosting), better spatial resolution, and an equivalent or better instrument resolution in powder diffraction than the MPA. These improvements will facilitate broader applications of WLSF detectors at time-of-flight neutron powder diffraction beamlines, including single-crystal diffraction and texture analysis. PMID- 27250411 TI - Novel pulsed particle accelerator for energy dependent positron re-emission experiments. AB - We report on a novel device for particle acceleration based on elevation of the potential energy of beam pulses. This so-called energy elevator is particularly beneficial if both the particle source and the sample have to be near ground potential due to experimental constraints. We applied this new technique to enable depth dependent measurements of re-emitted positrons using the surface spectrometer at the NEPOMUC positron beam facility. First, a two-stage bunching system is used to generate positron pulses with a repetition rate of 5 MHz and a duration of 1.663(5) ns before their energy is raised to several keV. The whole system was shown to work with an exceptional efficiency of 88%. We demonstrated the usability of our setup by investigating the positron re-emission spectra of Ni and Pd as function of positron implantation energy. For Ni the positron work function could be determined to be PhiNi (+)=-1.4(2)eV. In addition, as predicted by theory, our experimental findings imply a positive positron work function for Pd. PMID- 27250412 TI - Cold and intense OH radical beam sources. AB - We present the design and performance of two supersonic radical beam sources: a conventional pinhole-discharge source and a dielectric barrier discharge (DBD) source, both based on the Nijmegen pulsed valve. Both designs have been characterized by discharging water molecules seeded in the rare gases Ar, Kr, or Xe. The resulting OH radicals have been detected by laser-induced fluorescence. The measured OH densities are (3.0 +/- 0.6) * 10(11) cm(-3) and (1.0 +/- 0.5) * 10(11) cm(-3) for the pinhole-discharge and DBD sources, respectively. The beam profiles for both radical sources show a relative longitudinal velocity spread of about 10%. The absolute rotational ground state population of the OH beam generated from the pinhole-discharge source has been determined to be more than 98%. The DBD source even produces a rotationally colder OH beam with a population of the ground state exceeding 99%. For the DBD source, addition of O2 molecules to the gas mixture increases the OH beam density by a factor of about 2.5, improves the DBD valve stability, and allows to tune the mean velocity of the radical beam. PMID- 27250413 TI - Calibration of imaging plates to electrons between 40 and 180 MeV. AB - This paper presents the response calibration of Imaging Plates (IPs) for electrons in the 40-180 MeV range using laser-accelerated electrons at Laboratoire d'Optique Appliquee (LOA), Palaiseau, France. In the calibration process, the energy spectrum and charge of electron beams are measured by an independent system composed of a magnetic spectrometer and a Lanex scintillator screen used as a calibrated reference detector. It is possible to insert IPs of different types or stacks of IPs in this spectrometer in order to detect dispersed electrons simultaneously. The response values are inferred from the signal on the IPs, due to an appropriate charge calibration of the reference detector. The effect of thin layers of tungsten in front and/or behind IPs is studied in detail. GEANT4 simulations are used in order to analyze our measurements. PMID- 27250414 TI - Development and performance of a suprathermal electron spectrometer to study auroral precipitations. AB - The design, development, and performance of Medium-energy Electron SPectrometer (MESP), dedicated to the in situ observation of suprathermal electrons in the auroral ionosphere, are summarized in this paper. MESP employs a permanent magnet filter with a light tight structure to select electrons with proper energies guided to the detectors. A combination of two avalanche photodiodes and a large area solid-state detector (SSD) provided 46 total energy bins (1 keV resolution for 3-20 keV range for APDs, and 7 keV resolution for >20 keV range for SSDs). Multi-channel ultra-low power application-specific integrated circuits are also verified for the flight operation to read-out and analyze the detector signals. MESP was launched from Poker Flat Research Range on 3 March 2014 as a part of ground-to-rocket electrodynamics-electrons correlative experiment (GREECE) mission. MESP successfully measured the precipitating electrons from 3 to 120 keV in 120-ms time resolution and characterized the features of suprathermal distributions associated with auroral arcs throughout the flight. The measured electrons were showing the inverted-V type spectra, consistent with the past measurements. In addition, investigations of the suprathermal electron population indicated the existence of the energetic non-thermal distribution corresponding to the brightest aurora. PMID- 27250415 TI - High power microwave source with a three dimensional printed metamaterial slow wave structure. AB - For over the last decade, the concept of metamaterials has led to new approaches for considering the interaction of radiation with complex structures. However, practical manifestations of such a device operating at high power densities have proven difficult to achieve due to the resonant nature of metamaterials and the resultant high electric fields, which place severe constraints on manufacturing the slow wave structures. In this paper, we describe the first experimental manifestation of a high power microwave device utilizing a metallic slow wave structure (metamaterial-like) fabricated using additive manufacturing. The feasibility of utilizing additive manufacturing as a technique for building these relatively complicated structures has thus been demonstrated. The MW class microwave source operates in the C-band and shows frequency tunablility with electron beam voltage. The basic electromagnetic characteristics of this device, the construction using additive manufacturing, and the basic performance as a microwave oscillator are considered. Due to the tunable nature of the device, it shows promise not only as an oscillator but also as a microwave amplifier. Therefore, the dispersive characteristics and a discussion of the anticipated gain is included as it relates to an amplifier configuration. PMID- 27250416 TI - Energy deposition evaluation for ultra-low energy electron beam irradiation systems using calibrated thin radiochromic film and Monte Carlo simulations. AB - For evaluation of on-site dosimetry and process design in industrial use of ultra low energy electron beam (ULEB) processes, we evaluate the energy deposition using a thin radiochromic film and a Monte Carlo simulation. The response of film dosimeter was calibrated using a high energy electron beam with an acceleration voltage of 2 MV and alanine dosimeters with uncertainty of 11% at coverage factor 2. Using this response function, the results of absorbed dose measurements for ULEB were evaluated from 10 kGy to 100 kGy as a relative dose. The deviation between the responses of deposit energy on the films and Monte Carlo simulations was within 15%. As far as this limitation, relative dose estimation using thin film dosimeters with response function obtained by high energy electron irradiation and simulation results is effective for ULEB irradiation processes management. PMID- 27250417 TI - Neutron temporal diagnostic for high-yield deuterium-tritium cryogenic implosions on OMEGA. AB - A next-generation neutron temporal diagnostic (NTD) capable of recording high quality data for the highest anticipated yield cryogenic deuterium-tritium (DT) implosion experiments was recently installed at the Omega Laser Facility. A high quality measurement of the neutron production width is required to determine the hot-spot pressure achieved in inertial confinement fusion experiments-a key metric in assessing the quality of these implosions. The design of this NTD is based on a fast-rise-time plastic scintillator, which converts the neutron kinetic energy to 350- to 450-nm-wavelength light. The light from the scintillator inside the nose-cone assembly is relayed ~16 m to a streak camera in a well-shielded location. An ~200* reduction in neutron background was observed during the first high-yield DT cryogenic implosions compared to the current NTD installation on OMEGA. An impulse response of ~40 +/- 10 ps was measured in a dedicated experiment using hard x-rays from a planar target irradiated with a 10 ps short pulse from the OMEGA EP laser. The measured instrument response includes contributions from the scintillator rise time, optical relay, and streak camera. PMID- 27250419 TI - A simple spectroscopic method to determine the degree of dissociation in hydrogen plasmas with wide-range spectrometer. AB - A new and simple method for determining the degree of dissociation in hydrogen plasmas is presented. In this method, wide-range spectrum covering from an atomic H-gamma line (434.05 nm) to molecular Fulcher-alpha band (600-640 nm) is measured simultaneously by a wide-range miniature spectrometer. Since the wide-range spectrum measured by the miniature spectrometer is too broadened to resolve respective lines in the Fulcher-alpha band, a synthetic spectrum method is applied to improve the accuracy in the Q-branch of Fulcher-alpha band intensity measurement. In order to reduce the influence from other transitions or anomalous P- and R-branch of Fulcher-alpha spectrum, the Fulcher-alpha spectra of which vibrational states are higher than 1 (upsilon >= 1) are synthesized using the rotational temperature obtained by the 0-0 Fulcher-alpha spectrum. The degree of dissociation is determined from the intensity ratio between H-gamma line and the synthesized Fulcher-alpha band spectrum. A comparative study carried out in a volume-produced negative hydrogen ion source shows that the degree of dissociation determined by this method agrees well with the measured values using a spectrometer with high spectral resolution. The present method is expected to be useful to characterize the plasma sources with molecular species since it provides important parameters for understanding neutral particle behaviors. PMID- 27250418 TI - Three-dimensional tomographic imaging for dynamic radiation behavior study using infrared imaging video bolometers in large helical device plasma. AB - A three-dimensional (3D) tomography system using four InfraRed imaging Video Bolometers (IRVBs) has been designed with a helical periodicity assumption for the purpose of plasma radiation measurement in the large helical device. For the spatial inversion of large sized arrays, the system has been numerically and experimentally examined using the Tikhonov regularization with the criterion of minimum generalized cross validation, which is the standard solver of inverse problems. The 3D transport code EMC3-EIRENE for impurity behavior and related radiation has been used to produce phantoms for numerical tests, and the relative calibration of the IRVB images has been carried out with a simple function model of the decaying plasma in a radiation collapse. The tomography system can respond to temporal changes in the plasma profile and identify the 3D dynamic behavior of radiation, such as the radiation enhancement that starts from the inboard side of the torus, during the radiation collapse. The reconstruction results are also consistent with the output signals of a resistive bolometer. These results indicate that the designed 3D tomography system is available for the 3D imaging of radiation. The first 3D direct tomographic measurement of a magnetically confined plasma has been achieved. PMID- 27250420 TI - A method for coincidence timing resolution enhancement. AB - A method including the coincidence time resolution improvement for a TOF/positron emission tomography system was suggested. The spectrometer for this aim was composed of two NaI(Tl) and two plastic scintillation detectors. Experimental results were supported by FLUKA Monte Carlo simulation program by constructing the detector setup in software medium. Present experimental results verified our previous results and conclusions obtained from the suggested method. It was concluded that better resolutions would help the improvement not only on the TOF gain but also on the spatial resolution, leading to better images and helping the Physician in his/her diagnosis and treatment. PMID- 27250421 TI - Transport and trapping of dust particles in a potential well created by inductively coupled diffused plasmas. AB - A versatile linear dusty (complex) plasma device is designed to study the transport and dynamical behavior of dust particles in a large volume. Diffused inductively coupled plasma is generated in the background of argon gas. A novel technique is used to introduce the dust particles in the main plasma by striking a secondary direct current glow discharge. These dust particles are found to get trapped in an electrostatic potential well, which is formed due to the combination of the ambipolar electric field caused by diffusive plasma and the field produced by the charged glass wall of the vacuum chamber. According to the requirements, the volume of the dust cloud can be controlled very precisely by tuning the plasma and discharge parameters. The present device can be used to address the underlying physics behind the transport of dust particles, self excited dust acoustic waves, and instabilities. The detailed design of this device, plasma production and characterization, trapping and transport of the dust particle, and some of the preliminary experimental results are presented. PMID- 27250422 TI - Charge exchange recombination spectroscopy on the T-10 tokamak. AB - The charge exchange recombination spectroscopy (CXRS) diagnostics on the T-10 tokamak is described. The system is based on a diagnostic neutral beam and includes three high etendue spectrometers designed for the ITER edge CXRS system. A combined two-channel spectrometer is developed for simultaneous measurements of two beam-induced spectral lines using the same lines of sight. A basic element of the combined spectrometer is a transmitting holographic grating designed for the narrow spectral region 5291 +/- 100 A. The whole CXRS system provides simultaneous measurements of two CXRS impurity spectra and Halpha beam line. Ion temperature measurements are routinely provided using the C(6+) CXRS spectral line 5291 A. Simultaneous measurements of carbon densities and one more impurity (oxygen, helium, lithium etc.) are carried out. Two light collecting systems with 9 lines of sight in each system are used in the diagnostics. Spatial resolution is up to 2.5 cm and temporal resolution of 1 ms is defined by the diagnostic neutral beam diameter and pulse duration, respectively. Experimental results are shown to demonstrate a wide range of the CXRS diagnostic capabilities on T-10 for investigation of impurity transport processes in tokamak plasma. Developed diagnostics provides necessary experimental data for studying of plasma electric fields, heat and particle transport processes, and for investigation of geodesic acoustic modes. PMID- 27250423 TI - High-speed digital holography for neutral gas and electron density imaging. AB - An instrument was developed using digital holographic reconstruction of the wavefront from a CO2 laser imaged on a high-speed commercial IR camera. An acousto-optic modulator is used to generate 1-25 MUs pulses from a continuous wave CO2 laser, both to limit the average power at the detector and also to freeze motion from sub-interframe time scales. Extensive effort was made to characterize and eliminate noise from vibrations and second-surface reflections. Mismatch of the reference and object beam curvature initially contributed substantially to vibrational noise, but was mitigated through careful positioning of identical imaging lenses. Vibrational mode amplitudes were successfully reduced to ?1 nm for frequencies ?50 Hz, and the inter-frame noise across the 128 * 128 pixel window which is typically used is ?2.5 nm. To demonstrate the capabilities of the system, a piezo-electric valve and a reducing-expanding nozzle were used to generate a super-sonic gas jet which was imaged with high spatial resolution (better than 0.8 lp/mm) at high speed. Abel inversions were performed on the phase images to produce 2-D images of localized gas density. This system could also be used for high spatial and temporal resolution measurements of plasma electron density or surface deformations. PMID- 27250424 TI - Development and evaluation of a collection apparatus for recoil products for study of the deexcitation process of (235m)U. AB - The nucleus (235m)U is an isomer with extremely low excitation energy (76.8 eV) and decays dominantly through the internal conversion (IC) process. Because outer shell electrons are involved in the IC process, the decay constant of (235m)U depends on its chemical environment. We plan to study the deexcitation process of (235m)U by measuring the energy spectra of IC electrons in addition to the decay constants for various chemical forms. In this paper, the preparation method of (235m)U samples from (239)Pu by using alpha-recoil energy is reported. A Collection Apparatus for Recoil Products was fabricated, and then collection efficiencies under various conditions were determined by collecting (224)Ra recoiling out of (228)Th electrodeposited and precipitated sources. The pressure in the apparatus (vacuum or 1 atm of N2 gas) affected the variations of the collection efficiencies depending on the negative voltage applied to the collector. The maximum values of the collection efficiencies were mainly affected by the thickness of the (228)Th sources. From these results, the suitable conditions of the (239)Pu sources for preparation of (235m)U were determined. In addition, dissolution efficiencies were determined by washing collected (224)Ra with solutions. When (224)Ra was collected in 1 atm of N2 gas and dissolved with polar solutions such as water, the dissolution efficiencies were nearly 100%. The method of rapid dissolution of recoil products would be applicable to rapid preparation of short-lived (235m)U samples for various chemical forms. PMID- 27250425 TI - Real-time diamagnetic flux measurements on ASDEX Upgrade. AB - Real-time diamagnetic flux measurements are now available on ASDEX Upgrade. In contrast to the majority of diamagnetic flux measurements on other tokamaks, no analog summation of signals is necessary for measuring the change in toroidal flux or for removing contributions arising from unwanted coupling to the plasma and poloidal field coil currents. To achieve the highest possible sensitivity, the diamagnetic measurement and compensation coil integrators are triggered shortly before plasma initiation when the toroidal field coil current is close to its maximum. In this way, the integration time can be chosen to measure only the small changes in flux due to the presence of plasma. Two identical plasma discharges with positive and negative magnetic field have shown that the alignment error with respect to the plasma current is negligible. The measured diamagnetic flux is compared to that predicted by TRANSP simulations. The poloidal beta inferred from the diamagnetic flux measurement is compared to the values calculated from magnetic equilibrium reconstruction codes. The diamagnetic flux measurement and TRANSP simulation can be used together to estimate the coupled power in discharges with dominant ion cyclotron resonance heating. PMID- 27250426 TI - Bunker probe: A plasma potential probe almost insensitive to its orientation with the magnetic field. AB - Due to their ability to suppress a large part of the electron current and thus measuring directly the plasma potential, ion sensitive probes have begun to be widely tested and used in fusion devices. For these probes to work, almost perfect alignment with the total magnetic field is necessary. This condition cannot always be fulfilled due to the curvature of magnetic fields, complex magnetic structure, or magnetic field reconnection. In this perspective, we have developed a plasma potential probe (named Bunker probe) based on the principle of the ion sensitive probe but almost insensitive to its orientation with the total magnetic field. Therefore it can be used to measure the plasma potential inside fusion devices, especially in regions with complex magnetic field topology. Experimental results are presented and compared with Ball-Pen probe measurements taken under identical conditions. We have observed that the floating potential of the Bunker probe is indeed little affected by its orientation with the magnetic field for angles ranging from 90 degrees to 30 degrees , in contrast to the Ball Pen probe whose floating potential decreases towards that of a Langmuir probe if not properly aligned with the magnetic field. PMID- 27250427 TI - A picosecond beam-timing system for the OMEGA laser. AB - A timing system is demonstrated for the OMEGA Laser System that guarantees all 60 beams will arrive on target simultaneously with a root mean square variability of 4 ps. The system relies on placing a scattering sphere at the target position to couple the ultraviolet light from each beam into a single photodetector. PMID- 27250428 TI - Development of a magnetized coaxial plasma gun for compact toroid injection into the C-2 field-reversed configuration device. AB - A compact toroid (CT) injector was developed for the C-2 device, primarily for refueling of field-reversed configurations. The CTs are formed by a magnetized coaxial plasma gun (MCPG), which consists of coaxial cylindrical electrodes and a bias coil for creating a magnetic field. First, a plasma ring is generated by a discharge between the electrodes and is accelerated by Lorenz self-force. Then, the plasma ring is captured by an interlinkage flux (poloidal flux). Finally, the fully formed CT is ejected from the MCPG. The MCPG described herein has two gas injection ports that are arranged tangentially on the outer electrode. A tungsten coated inner electrode has a head which can be replaced with a longer one to extend the length of the acceleration region for the CT. The developed MCPG has achieved supersonic CT velocities of ~100 km/s. Plasma parameters for electron density, electron temperature, and the number of particles are ~5 * 10(21) m(-3), ~40 eV, and 0.5-1.0 * 10(19), respectively. PMID- 27250429 TI - A broadband toolbox for scanning microwave microscopy transmission measurements. AB - In this paper, we present in detail the design, both electromagnetic and mechanical, the fabrication, and the test of the first prototype of a Scanning Microwave Microscope (SMM) suitable for a two-port transmission measurement, recording, and processing the high frequency transmission scattering parameter S21 passing through the investigated sample. The S21 toolbox is composed by a microwave emitter, placed below the sample, which excites an electromagnetic wave passing through the sample under test, and is collected by the cantilever used as the detector, electrically matched for high frequency measurements. This prototype enhances the actual capability of the instrument for a sub-surface imaging at the nanoscale. Moreover, it allows the study of the electromagnetic properties of the material under test obtained through the measurement of the reflection (S11) and transmission (S21) parameters at the same time. The SMM operates between 1 GHz and 20 GHz, current limit for the microwave matching of the cantilever, and the high frequency signal is recorded by means of a two-port Vector Network Analyzer, using both contact and no-contact modes of operation, the latter, especially minded for a fully nondestructive and topography-free characterization. This tool is an upgrade of the already established setup for the reflection mode S11 measurement. Actually, the proposed setup is able to give richer information in terms of scattering parameters, including amplitude and phase measurements, by means of the two-port arrangement. PMID- 27250430 TI - Fast time-resolved electrostatic force microscopy: Achieving sub-cycle time resolution. AB - The ability to measure microsecond- and nanosecond-scale local dynamics below the diffraction limit with widely available atomic force microscopy hardware would enable new scientific studies in fields ranging from biology to semiconductor physics. However, commercially available scanning-probe instruments typically offer the ability to measure dynamics only on time scales of milliseconds to seconds. Here, we describe in detail the implementation of fast time-resolved electrostatic force microscopy using an oscillating cantilever as a means to measure fast local dynamics following a perturbation to a sample. We show how the phase of the oscillating cantilever relative to the perturbation event is critical to achieving reliable sub-cycle time resolution. We explore how noise affects the achievable time resolution and present empirical guidelines for reducing noise and optimizing experimental parameters. Specifically, we show that reducing the noise on the cantilever by using photothermal excitation instead of piezoacoustic excitation further improves time resolution. We demonstrate the discrimination of signal rise times with time constants as fast as 10 ns, and simultaneous data acquisition and analysis for dramatically improved image acquisition times. PMID- 27250431 TI - Operando x-ray photoelectron emission microscopy for studying forward and reverse biased silicon p-n junctions. AB - Significant progress in the understanding of surfaces and interfaces of materials for new technologies requires operando studies, i.e., measurement of chemical, electronic, and magnetic properties under external stimulus (such as mechanical strain, optical illumination, or electric fields) applied in situ in order to approach real operating conditions. Electron microscopy attracts much interest, thanks to its ability to determine semiconductor doping at various scales in devices. Spectroscopic photoelectron emission microscopy (PEEM) is particularly powerful since it combines high spatial and energy resolution, allowing a comprehensive analysis of local work function, chemistry, and electronic structure using secondary, core level, and valence band electrons, respectively. Here we present the first operando spectroscopic PEEM study of a planar Si p-n junction under forward and reverse bias. The method can be used to characterize a vast range of materials at near device scales such as resistive oxides, conducting bridge memories and domain wall arrays in ferroelectrics photovoltaic devices. PMID- 27250432 TI - High-resolution fully vectorial scanning Kerr magnetometer. AB - We report on the development of a high-resolution scanning magnetometer, which fully exploits the vectorial nature of the magneto-optical Kerr effect. The three dimensional nature of magnetization is at the basis of many micromagnetic phenomena and from these data, we can fully characterize magnetization processes of nanostructures in static and dynamic regimes. Our scanning Kerr magnetometer uses a high numerical aperture microscope objective where the incident light beam can be deterministically deviated from the objective symmetry axis, therefore, both in-plane (via the longitudinal Kerr effect) and out-of-plane (via the polar Kerr effect) components of the magnetization vector may be detected. These components are then separated by exploiting the symmetries of the polar and longitudinal Kerr effects. From four consecutive measurements, we are able to directly obtain the three orthogonal components of the magnetization vector with a resolution of 600 nm. Performance of the apparatus is demonstrated by a measurement of 3D magnetization vector maps showing out-of-plane domains and in plane domain walls in an yttrium-iron-garnet film and on a study of magnetization reversal in a 4-MUm-wide magnetic disk. PMID- 27250433 TI - Automated force controller for amplitude modulation atomic force microscopy. AB - Atomic Force Microscopy (AFM) is widely used in physics, chemistry, and biology to analyze the topography of a sample at nanometer resolution. Controlling precisely the force applied by the AFM tip to the sample is a prerequisite for faithful and reproducible imaging. In amplitude modulation (oscillating) mode AFM, the applied force depends on the free and the setpoint amplitudes of the cantilever oscillation. Therefore, for keeping the applied force constant, not only the setpoint amplitude but also the free amplitude must be kept constant. While the AFM user defines the setpoint amplitude, the free amplitude is typically subject to uncontrollable drift, and hence, unfortunately, the real applied force is permanently drifting during an experiment. This is particularly harmful in biological sciences where increased force destroys the soft biological matter. Here, we have developed a strategy and an electronic circuit that analyzes permanently the free amplitude of oscillation and readjusts the excitation to maintain the free amplitude constant. As a consequence, the real applied force is permanently and automatically controlled with picoNewton precision. With this circuit associated to a high-speed AFM, we illustrate the power of the development through imaging over long-duration and at various forces. The development is applicable for all AFMs and will widen the applicability of AFM to a larger range of samples and to a larger range of (non specialist) users. Furthermore, from controlled force imaging experiments, the interaction strength between biomolecules can be analyzed. PMID- 27250434 TI - Optical imaging module for astigmatic detection system. AB - In this paper, an optical imaging module design for an astigmatic detection system (ADS) is presented. The module is based on a commercial optical pickup unit (OPU) and it contains a coaxial illuminant for illuminating a specimen. Furthermore, the imaging module facilitates viewing the specimen and the detection laser spot of the ADS with a lateral resolution of approximately 1 MUm without requiring the removal of an element of the OPU. Two polarizers and one infrared filter are used to eliminate stray laser light in the OPU and stray light produced by the illuminant. Imaging modules designed for digital versatile disks (DVDs) and Blu-ray DVDs were demonstrated. Furthermore, the module can be used for imaging a small cantilever with approximate dimensions of 2 MUm (width) * 5 MUm (length), and therefore, it has the potential to be used in high-speed atomic force microscopy. PMID- 27250435 TI - Development of a spectroscopic Mueller matrix imaging ellipsometer for nanostructure metrology. AB - In this paper, we describe the development of a spectroscopic Mueller matrix imaging ellipsometer (MMIE), which combines the great power of Mueller matrix ellipsometry with the high spatial resolution of optical microscopy. A dual rotating-compensator configuration is adopted to collect the full 4 * 4 imaging Mueller matrix in a single measurement. The light wavelengths are scanned in the range of 400-700 nm by a monochromator. The instrument has measurement accuracy and precision better than 0.01 for all the Mueller matrix elements in both the whole image and the whole spectral range. The instrument was then applied for the measurement of nanostructures combined with an inverse diffraction problem solving technique. The experiment performed on a photoresist grating sample has demonstrated the great potential of MMIE for accurate grating reconstruction from spectral data collected by a single pixel of the camera and for efficient quantification of geometrical profile of the grating structure over a large area with pixel resolution. It is expected that MMIE will be a powerful tool for nanostructure metrology in future high-volume nanomanufacturing. PMID- 27250436 TI - Stress measurements of planar dielectric elastomer actuators. AB - Dielectric elastomer actuator (DEA) micro- and nano-structures are referred to artificial muscles because of their specific continuous power and adequate time response. The bending measurement of an asymmetric, planar DEA is described. The asymmetric cantilevers consist of 1 or 5 MUm-thin DEAs deposited on polyethylene naphthalate (PEN) substrates 16, 25, 38, or 50 MUm thick. The application of a voltage to the DEA electrodes generates an electrostatic pressure in the sandwiched silicone elastomer layer, which causes the underlying PEN substrate to bend. Optical beam deflection enables the detection of the bending angle vs. applied voltage. Bending radii as large as 850 m were reproducibly detected. DEA tests with electric fields of up to 80 V/MUm showed limitations in electrode's conductivity and structure failures. The actuation measurement is essential for the quantitative characterization of nanometer-thin, low-voltage, single- and multi-layer DEAs, as foreseen for artificial sphincters to efficiently treat severe urinary and fecal incontinence. PMID- 27250437 TI - Temperature calibration for diffusion experiments to sub-Kelvin precision. AB - Arrhenius plots are often used to determine energy barriers and prefactors of thermally activated processes. The precision of thus determined values depends crucially on the precision of the temperature measurement at the sample surface. We line out a procedure to determine the absolute temperature of a metal sample in a cryogenic scanning tunneling microscope between 5 K and 50 K with sub-Kelvin precision. We demonstrate the dependence of prefactor and diffusion energy on this calibration for diffusion of CO on Cu(111) and on Ag(100) measured in the temperature range from 30 K to 38 K and 19 K to 23 K, respectively. PMID- 27250438 TI - Simultaneous, single-pulse, synchrotron x-ray imaging and diffraction under gas gun loading. AB - We develop a mini gas gun system for simultaneous, single-pulse, x-ray diffraction and imaging under high strain-rate loading at the beamline 32-ID of the Advanced Photon Source. In order to increase the reciprocal space covered by a small-area detector, a conventional target chamber is split into two chambers: a narrowed measurement chamber and a relief chamber. The gas gun impact is synchronized with synchrotron x-ray pulses and high-speed cameras. Depending on a camera's capability, multiframe imaging and diffraction can be achieved. The proof-of-principle experiments are performed on single-crystal sapphire. The diffraction spots and images during impact are analyzed to quantify lattice deformation and fracture; fracture is dominated by splitting cracks followed by wing cracks, and diffraction peaks are broadened likely due to mosaic spread. Our results demonstrate the potential of such multiscale measurements for studying high strain-rate phenomena at dynamic extremes. PMID- 27250439 TI - Broadband, large-area microwave antenna for optically detected magnetic resonance of nitrogen-vacancy centers in diamond. AB - We report on a microwave planar ring antenna specifically designed for optically detected magnetic resonance (ODMR) of nitrogen-vacancy (NV) centers in diamond. It has the resonance frequency at around 2.87 GHz with the bandwidth of 400 MHz, ensuring that ODMR can be observed under external magnetic fields up to 100 G without the need of adjustment of the resonance frequency. It is also spatially uniform within the 1-mm-diameter center hole, enabling the magnetic-field imaging in the wide spatial range. These features facilitate the experiments on quantum sensing and imaging using NV centers at room temperature. PMID- 27250440 TI - Contactless electrical conductivity measurement of metallic submicron-grain material: Application to the study of aluminum with severe plastic deformation. AB - We measured the electrical conductivity sigma of aluminum specimen consisting of submicron-grains by observing the AC magnetic susceptibility resulting from the eddy current. By using a commercial platform for magnetic measurement, contactless measurement of the relative electrical conductivity sigman of a nonmagnetic metal is possible over a wide temperature (T) range. By referring to sigma at room temperature, obtained by the four-terminal method, sigman(T) was transformed into sigma(T). This approach is useful for cylinder specimens, in which the estimation of the radius and/or volume is difficult. An experiment in which aluminum underwent accumulative roll bonding, which is a severe plastic deformation process, validated this method of evaluating sigma as a function of the fraction of high-angle grain boundaries. PMID- 27250441 TI - High accuracy calibration of a dynamic vapor sorption instrument and determination of the equilibrium humidities using single salts. AB - We present a procedure for accurately calibrating a dynamic vapor sorption (DVS) instrument using single salts. The procedure accounts for and tailors distinct calibration tests according to the fundamental properties of each salt. Especially relevant properties influencing the calibration are the heat of solution, heat of condensation, and the kinetics connected to the salt phase transition, as these influence the microclimate surrounding the salts during calibration. All these issues were dealt with to obtain precise calibration results. The DVS instrument comprises two control modes to generate and measure the relative humidity (RH). Both control modes were separately examined and combined to overcome the shortcomings of each of the two control modes and thereby obtain the most accurate results. Repeated calibration testing with the single salts (LiCl, MgCl2, Mg(NO3)2, NaCl, and KNO3) enables five discrete sorption isotherm measurements within the range of 11%-93%RH. The equilibrium RH of the solution for LiCl, MgCl2, Mg(NO3)2, NaCl, and KNO3 was determined with a standard deviation of 0.06%-0.15% (0.45% for KNO3) RH. By comparing the measured calibration values with the well-known equilibrium RH of each salt solution, the presented method's results are both accurate with significant agreement and precise with small variation. PMID- 27250442 TI - An instrument to measure fast gas phase radical kinetics at high temperatures and pressures. AB - Fast radical reactions are central to the chemistry of planetary atmospheres and combustion systems. Laser-induced fluorescence is a highly sensitive and selective technique that can be used to monitor a number of radical species in kinetics experiments, but is typically limited to low pressure systems owing to quenching of fluorescent states at higher pressures. The design and characterisation of an instrument are reported using laser-induced fluorescence detection to monitor fast radical kinetics (up to 25 000 s(-1)) at high temperatures and pressures by sampling from a high pressure reaction region to a low pressure detection region. Kinetics have been characterised at temperatures reaching 740 K and pressures up to 2 atm, with expected maximum operational conditions of up to ~900 K and ~5 atm. The distance between the point of sampling from the high pressure region and the point of probing within the low pressure region is critical to the measurement of fast kinetics. The instrumentation described in this work can be applied to the measurement of kinetics relevant to atmospheric and combustion chemistry. PMID- 27250443 TI - Measurements of fluid viscosity using a miniature ball drop device. AB - This paper describes measurement of fluid viscosity using a small ball drop device. It requires as little as 100 MUl of fluid. Each measurement can be performed in seconds. The experiment is designed to yield reliable viscosity values by operating at properly chosen tilt angles and with calibration using well-characterized Newtonian fluids such as mixtures of glycerol and water. It also yields dynamical viscosity of non-Newtonian fluids at moderate shear rates. The device is easy to assemble and it allows for the measurement of viscosity even when the fluid samples are too small to measure using most commercial viscometers or rheometers. Therefore, the technique is particularly useful in characterizing biological fluids such as solutions of proteins, DNA, and polymers frequently used in biomaterial applications. PMID- 27250444 TI - Development of a low noise induction magnetic sensor using magnetic flux negative feedback in the time domain. AB - Time-domain electromagnetic system can implement great depth detection. As for the electromagnetic system, the receiver utilized an air coil sensor, and the matching mode of the sensor employed the resistance matching method. By using the resistance matching method, the vibration of the coil in the time domain can be effectively controlled. However, the noise of the sensor, especially the noise at the resonance frequency, will be increased as well. In this paper, a novel design of a low noise induction coil sensor is proposed, and the experimental data and noise characteristics are provided. The sensor is designed based on the principle that the amplified voltage will be converted to current under the influence of the feedback resistance of the coil. The feedback loop around the induction coil exerts a magnetic field and sends the negative feedback signal to the sensor. The paper analyses the influence of the closed magnetic feedback loop on both the bandwidth and the noise of the sensor. The signal-to-noise ratio is improved dramatically. PMID- 27250445 TI - A broadband micro-machined far-infrared absorber. AB - The experimental investigation of a broadband far-infrared meta-material absorber is described. The observed absorptance is >0.95 from 1 to 20 THz (300-15 MUm) over a temperature range spanning 5-300 K. The meta-material, realized from an array of tapers ~100 MUm in length, is largely insensitive to the detailed geometry of these elements and is cryogenically compatible with silicon-based micro-machined technologies. The electromagnetic response is in general agreement with a physically motivated transmission line model. PMID- 27250446 TI - Time-frequency energy density precipitation method for time-of-flight extraction of narrowband Lamb wave detection signals. AB - The time-of-flight of the Lamb wave provides an important basis for defect evaluation in metal plates and is the input signal for Lamb wave tomographic imaging. However, the time-of-flight can be difficult to acquire because of the Lamb wave dispersion characteristics. This work proposes a time-frequency energy density precipitation method to accurately extract the time-of-flight of narrowband Lamb wave detection signals in metal plates. In the proposed method, a discrete short-time Fourier transform is performed on the narrowband Lamb wave detection signals to obtain the corresponding discrete time-frequency energy density distribution. The energy density values at the center frequency for all discrete time points are then calculated by linear interpolation. Next, the time domain energy density curve focused on that center frequency is precipitated by least squares fitting of the calculated energy density values. Finally, the peak times of the energy density curve obtained relative to the initial pulse signal are extracted as the time-of-flight for the narrowband Lamb wave detection signals. An experimental platform is established for time-of-flight extraction of narrowband Lamb wave detection signals, and sensitivity analysis of the proposed time-frequency energy density precipitation method is performed in terms of propagation distance, dispersion characteristics, center frequency, and plate thickness. For comparison, the widely used Hilbert-Huang transform method is also implemented for time-of-flight extraction. The results show that the time frequency energy density precipitation method can accurately extract the time-of flight with relative error of <1% and thus can act as a universal time-of-flight extraction method for narrowband Lamb wave detection signals. PMID- 27250447 TI - An X-band waveguide measurement technique for the accurate characterization of materials with low dielectric loss permittivity. AB - In this work, we present a new X-band waveguide (WR90) measurement method that permits the broadband characterization of the complex permittivity for low dielectric loss tangent material specimens with improved accuracy. An electrically long polypropylene specimen that partially fills the cross-section is inserted into the waveguide and the transmitted scattering parameter (S21) is measured. The extraction method relies on computational electromagnetic simulations, coupled with a genetic algorithm, to match the experimental S21 measurement. The sensitivity of the technique to sample length was explored by simulating specimen lengths from 2.54 to 15.24 cm, in 2.54 cm increments. Analysis of our simulated data predicts the technique will have the sensitivity to measure loss tangent values on the order of 10(-3) for materials such as polymers with relatively low real permittivity values. The ability to accurately characterize low-loss dielectric material specimens of polypropylene is demonstrated experimentally. The method was validated by excellent agreement with a free-space focused-beam system measurement of a polypropylene sheet. This technique provides the material measurement community with the ability to accurately extract material properties of low-loss material specimen over the entire X-band range. This technique could easily be extended to other frequency bands. PMID- 27250448 TI - Characteristics of a four element gyromagnetic nonlinear transmission line array high power microwave source. AB - In this paper, a solid-state four element array gyromagnetic nonlinear transmission line high power microwave system is presented as well as a detailed description of its subsystems and general output capabilities. This frequency agile S-band source is easily adjusted from 2-4 GHz by way of a DC driven biasing magnetic field and is capable of generating electric fields of 7.8 kV/m at 10 m correlating to 4.2 MW of RF power with pulse repetition frequencies up to 1 kHz. Beam steering of the array at angles of +/-16.7 degrees is also demonstrated, and the associated general radiation pattern is detailed. PMID- 27250449 TI - Waveguide transition with vacuum window for multiband dynamic nuclear polarization systems. AB - A low loss waveguide transition section and oversized microwave vacuum window covering several frequency bands (94 GHz, 140 GHz, 188 GHz) is presented. The transition is compact and was optimized for multiband Dynamic Nuclear Polarization (DNP) systems in a full-wave simulator. The window is more broadband than commercially available windows, which are usually optimized for single band operation. It is demonstrated that high-density polyethylene with urethane adhesive can be used as a low loss microwave vacuum window in multiband DNP systems. The overall assembly performance and dimensions are found using full wave simulations. The practical aspects of the window implementation in the waveguide are discussed. To verify the design and simulation results, the window is tested experimentally at the three frequencies of interest. PMID- 27250450 TI - A low noise and high precision linear power supply with thermal foldback protection. AB - A low noise and high precision linear power supply was designed for use in rare event search experiments with macrobolometers. The circuit accepts at the input a "noisy" dual supply voltage up to +/-15 V and gives at the output precise, low noise, and stable voltages that can be set between +/-3.75 V and +/-12.5 V in eight 1.25 V steps. Particular care in circuit design, component selection, and proper filtering results in a noise spectral density of 50nV/Hz at 1 Hz and 20nV/Hz white when the output is set to +/-5 V. This corresponds to 125 nV RMS (0.8 MUV peak to peak) between 0.1 Hz and 10 Hz, and 240 nV RMS (1.6 MUV peak to peak) between 0.1 Hz and 100 Hz. The power supply rejection ratio (PSRR) of the circuit is 100 dB at low frequency, and larger than 40 dB up to high frequency, thanks to a proper compensation design. Calibration allows to reach a precision in the absolute value of the output voltage of +/-70 ppm, or +/-350 MUV at +/-5 V, and to reduce thermal drifts below +/-1 ppm/(?)C in the expected operating range. The maximum peak output current is about 6 A from each output. An original foldback protection scheme was developed that dynamically limits the maximum output current to keep the temperature of the output transistors within their safe operating range. An add-on card based on an ARM Cortex-M3 microcontroller is devoted to the monitoring and control of all circuit functionalities and provides remote communication via CAN bus. PMID- 27250451 TI - Autonomous portable pulsed-periodical generator of high-power radiofrequency pulses based on gas discharge with hollow cathode. AB - Portable autonomous generator of high-power RF-pulses based on the gas discharge with hollow cathode has been designed, fabricated, and tested. Input and output characteristics are the following: discharge current amplitude is 800 A, duration of generated RF-pulses is 350 ns, carrier frequency is ~90 MHz, power in RF-pulse is 0.5 MW, pulse repetition rate is 0.5 kHz, and device efficiency is ~25%. PMID- 27250452 TI - High-speed, high-voltage pulse generation using avalanche transistor. AB - In this work, the conduction mechanism of avalanche transistors was demonstrated and the operation condition for generating high-speed pulse using avalanche transistors was illustrated. Based on the above analysis, a high-speed and high voltage pulse (HHP) generating circuit using avalanche transistors was designed, and its working principle and process were studied. To improve the speed of the output pulse, an approach of reducing the rise time of the leading edge is proposed. Methods for selecting avalanche transistor and reducing the parasitic inductance and capacitance of printed circuit board (PCB) were demonstrated. With these instructions, a PCB with a tapered transmission line was carefully designed and manufactured. Output pulse with amplitude of 2 kV and rise time of about 200 ps was realized with this PCB mounted with avalanche transistors FMMT417, indicating the effectiveness of the HHP generating circuit design. PMID- 27250453 TI - Nine-channel mid-power bipolar pulse generator based on a field programmable gate array. AB - Many channel arbitrary pulse sequence generation is required for the electro optic reconfiguration of optical waveguide networks in Lithium Niobate. Here we describe a scalable solution to the requirement for mid-power bipolar parallel outputs, based on pulse patterns generated by an externally clocked field programmable gate array. Positive and negative pulses can be generated at repetition rates up to 80 MHz with pulse width adjustable in increments of 1.6 ns across nine independent outputs. Each channel can provide 1.5 W of RF power and can be synchronised with the operation of other components in an optical network such as light sources and detectors through an external clock with adjustable delay. PMID- 27250454 TI - An improved model to predict bandwidth enhancement in an inductively tuned common source amplifier. AB - This paper presents an improved model for the prediction of bandwidth enhancement factor (BWEF) in an inductively tuned common source amplifier. In this model, we have included the effect of drain-source channel resistance of field effect transistor along with load inductance and output capacitance on BWEF of the amplifier. A frequency domain analysis of the model is performed and a closed form expression is derived for BWEF of the amplifier. A prototype common source amplifier is designed and tested. The BWEF of amplifier is obtained from the measured frequency response as a function of drain current and load inductance. In the present work, we have clearly demonstrated that inclusion of drain-source channel resistance in the proposed model helps to estimate the BWEF, which is accurate to less than 5% as compared to the measured results. PMID- 27250455 TI - Oscillator metrology with software defined radio. AB - Analog electrical elements such as mixers, filters, transfer oscillators, isolating buffers, dividers, and even transmission lines contribute technical noise and unwanted environmental coupling in time and frequency measurements. Software defined radio (SDR) techniques replace many of these analog components with digital signal processing (DSP) on rapidly sampled signals. We demonstrate that, generically, commercially available multi-channel SDRs are capable of time and frequency metrology, outperforming purpose-built devices by as much as an order-of-magnitude. For example, for signals at 10 MHz and 6 GHz, we observe SDR time deviation noise floors of about 20 fs and 1 fs, respectively, in under 10 ms of averaging. Examining the other complex signal component, we find a relative amplitude measurement instability of 3 * 10(-7) at 5 MHz. We discuss the scalability of a SDR-based system for simultaneous measurement of many clocks. SDR's frequency agility allows for comparison of oscillators at widely different frequencies. We demonstrate a novel and extreme example with optical clock frequencies differing by many terahertz: using a femtosecond-laser frequency comb and SDR, we show femtosecond-level time comparisons of ultra-stable lasers with zero measurement dead-time. PMID- 27250456 TI - Detecting leaks in gas-filled pressure vessels using acoustic resonances. AB - We demonstrate that a leak from a large, unthermostatted pressure vessel into ambient air can be detected an order of magnitude more effectively by measuring the time dependence of the ratio p/f(2) than by measuring the ratio p/T. Here f is the resonance frequency of an acoustic mode of the gas inside the pressure vessel, p is the pressure of the gas, and T is the kelvin temperature measured at one point in the gas. In general, the resonance frequencies are determined by a mode-dependent, weighted average of the square of the speed-of-sound throughout the volume of the gas. However, the weighting usually has a weak dependence on likely temperature gradients in the gas inside a large pressure vessel. Using the ratio p/f(2), we measured a gas leak (dM/dt)/M ~ - 1.3 * 10(-5) h(-1) = - 0.11 yr(-1) from a 300-liter pressure vessel filled with argon at 450 kPa that was exposed to sunshine-driven temperature and pressure fluctuations as large as (dT/dt)/T ~ (dp/dt)/p ~ 5 * 10(-2) h(-1) using a 24-hour data record. This leak could not be detected in a 72-hour record of p/T. (Here M is the mass of the gas in the vessel and t is the time.). PMID- 27250457 TI - Nanosecond-resolved temperature measurements using magnetic nanoparticles. AB - Instantaneous and noninvasive temperature measurements are important when laser thermotherapy or welding is performed. A noninvasive nanosecond-resolved magnetic nanoparticle (MNP) temperature measurement system is described in which a transient change in temperature causes an instantaneous change in the magnetic susceptibilities of the MNPs. These transient changes in the magnetic susceptibilities are rapidly recorded using a wideband magnetic measurement system with an upper frequency limit of 0.5 GHz. The Langevin function (the thermodynamic model characterizing the MNP magnetization process) is used to obtain the temperature information. Experiments showed that the MNP DC magnetization temperature-measurement system can detect a 14.4 ns laser pulse at least. This method of measuring temperature is likely to be useful for acquiring the internal temperatures of materials irradiated with lasers, as well as in other areas of research. PMID- 27250459 TI - Simultaneous measurement of heat capacity and internal relaxation time. AB - A new steady-state method is proposed to simultaneously measure the heat capacity and internal relaxation time using superimposed constant and square-wave power. This method is appropriate for small sample systems with low thermal conductance. The accuracies of the heat capacity and internal relaxation time are almost the same as those determined using other similar methods, but correction for the effect of internal relaxation on the heat capacity is more flexible. The thermal diffusivity and thermal conductivity are also simultaneously determined for rod- and slab-shaped samples. We demonstrate the method for small slabs of synthetic silica in the 80-320 K temperature range. PMID- 27250458 TI - Ultrasonic power measurement system based on acousto-optic interaction. AB - Ultrasonic waves are widely used, with applications including the medical, military, and chemical fields. However, there are currently no effective methods for ultrasonic power measurement. Previously, ultrasonic power measurement has been reliant on mechanical methods such as hydrophones and radiation force balances. This paper deals with ultrasonic power measurement based on an unconventional method: acousto-optic interaction. Compared with mechanical methods, the optical method has a greater ability to resist interference and also has reduced environmental requirements. Therefore, this paper begins with an experimental determination of the acoustic power in water contained in a glass tank using a set of optical devices. Because the light intensity of the diffraction image generated by acousto-optic interaction contains the required ultrasonic power information, specific software was written to extract the light intensity information from the image through a combination of filtering, binarization, contour extraction, and other image processing operations. The power value can then be obtained rapidly by processing the diffraction image using a computer. The results of this work show that the optical method offers advantages that include accuracy, speed, and a noncontact measurement method. PMID- 27250460 TI - Pulse wave detection method based on the bio-impedance of the wrist. AB - The real-time monitoring of pulse rate can evaluate the heart health to some extent, and the measurement of bio-impedance has the potential in wearable health monitoring system. In this paper, an effective method, which contains self balancing bridge, flexible electrode, and high-speed digital lock-in algorithm (DLIA) with over-sampling, was designed to detect the impedance pulse wave at the wrist. By applying the self-balancing bridge, the basic impedance can be compensated as much as possible, and the low amplitude of impedance variation related to heart pulse can be obtained more easily. And the flexible conductive rubber electrode used in our experiment is human-friendly. Besides, the over sampling method and high-speed DLIA are used to enhance the effective resolution of the existing data sampled by analog to digital converter. With the high-speed data process and simple circuit above, this proposed method has the potential in wrist-band wearable systems and it can satisfy quests of small volume and low power consumption. PMID- 27250461 TI - Design of single-phase driven screw-thread-type ultrasonic motor. AB - Most screw-thread-type ultrasonic motors are designed to be two-phase driven. This paper aims to present a novel single phase driven design that generates the required wobble motion, thus significantly simplifying the driving circuit of the ultrasonic motor. The proposed single-phase driven screw-thread-type ultrasonic motor works with two orthogonal bending modes generated by an asymmetric stator design. The novel stator design can improve the vibration displacement and further enhance the performance of the single phase driven motor. The vibration characteristics of the asymmetric stator structure were analyzed by ANSYS finite element analysis software. Based on the design and analysis processes, a prototype of the desired screw-thread-type ultrasonic motor was fabricated and tested. When the operating voltage is 200 Vpp, the obtained main characteristics of the proposed motor are as follows: the working frequency is between 28.3 and 29.5 kHz; the maximum no-load velocity is approximately 4.1 mm s(-1); and the thrust force is 1.6 N. PMID- 27250462 TI - Construction and characterization of a frequency-controlled, picometer resolution, displacement encoder-actuator. AB - We have constructed an actuator/encoder whose generated displacement is controlled through the resonance frequency of a microwave cavity. A compact, 10 MUm-range, digitally controlled actuator executing frequency-coded displacement with picometer resolution is described. We consider this approach particularly suitable for metrologic-precision scanning probe microscopy. PMID- 27250463 TI - Miniature hemispherical shell resonator with large-scale effective electrodes based on piezoelectric drive mechanism. AB - Miniature resonators with three-dimensional curved surface are mostly driven by electrostatic capacitive. However, it is quite difficult to fabricate a curved surface electrostatic resonator with large-scale effective electrodes. This paper presents the first miniature hemispherical shell resonator with large-scale effective electrodes based on piezoelectric drive mechanism. The vibrating body and electrodes of the piezoelectric resonator are easily integrated without micro scale or nano-scale narrow capacitive gap. Vibration experiment and finite element analysis both reveal that there exist seven significant vibration modes between 10 kHz and 100 kHz. Mode shape validation is also carried out by measuring the vibration velocity of upper perimeter and lateral perimeter with laser doppler vibrometer. Special vibration characteristics of each vibration mode are described in detail, based on which the resonator may be used for many specific applications. Compared with common electrostatic resonators, even smaller drive voltage applied to the piezoelectric resonator may produce larger vibration displacement at atmosphere. According to the experiment results, the resonator may provide a new way of realizing high performance three-dimensional miniature devices for communication and inertial navigation applications. PMID- 27250464 TI - A multi-probe thermophoretic soot sampling system for high-pressure diffusion flames. AB - Optical diagnostics and physical probing of the soot processes in high pressure combustion pose challenges that are not faced in atmospheric flames. One of the preferred methods of studying soot in atmospheric flames is in situ thermophoretic sampling followed by transmission electron microscopy imaging and analysis for soot sizing and morphology. The application of this method of sampling to high pressures has been held back by various operational and mechanical problems. In this work, we describe a rotating disk multi-probe thermophoretic soot sampling system, driven by a microstepping stepper motor, fitted into a high-pressure chamber capable of producing sooting laminar diffusion flames up to 100 atm. Innovative aspects of the sampling system design include an easy and precise control of the sampling time down to 2.6 ms, avoidance of the drawbacks of the pneumatic drivers used in conventional thermophoretic sampling systems, and the capability to collect ten consecutive samples in a single experimental run. Proof of principle experiments were performed using this system in a laminar diffusion flame of methane, and primary soot diameter distributions at various pressures up to 10 atm were determined. High-speed images of the flame during thermophoretic sampling were recorded to assess the influence of probe intrusion on the flow field of the flame. PMID- 27250465 TI - Simple locking of infrared and ultraviolet diode lasers to a visible laser using a LabVIEW proportional-integral-derivative controller on a Fabry-Perot signal. AB - Simultaneous laser locking of infrared (IR) and ultraviolet lasers to a visible stabilized reference laser is demonstrated via a Fabry-Perot (FP) cavity. LabVIEW is used to analyze the input, and an internal proportional-integral-derivative algorithm converts the FP signal to an analog locking feedback signal. The locking program stabilized both lasers to a long term stability of better than 9 MHz, with a custom-built IR laser undergoing significant improvement in frequency stabilization. The results of this study demonstrate the viability of a simple, computer-controlled, non-temperature-stabilized FP locking scheme for our applications, laser cooling of Ca(+) ions, and its use in other applications with similar modest frequency stabilization requirements. PMID- 27250466 TI - Method for measuring settling phenomena by means of frequency domain instrumentation. AB - The paper deals with the analysis of settling phenomena that characterize the step response of digital to analog converters, amplifiers, and several other devices. Settling is described by means of a minimal second order model that is suitable to account for the distortion terms recognized in the signal spectrum. An alternative method for dynamic performance assessment of systems characterized by poor settling performance is then proposed. Thanks to the use of high bandwidth spectrum analyzers, the proposed method overtakes the limits characterizing the measurement approaches based on the use of time-domain instruments in the presence of modern ultra-wideband systems. PMID- 27250467 TI - Automatic outdoor monitoring system for photovoltaic panels. AB - Long-term acquisition of solar panel performance parameters, for panels operated at maximum power point in their real environment, is of critical importance in the photovoltaic research sector. However, few options exist for the characterization of non-standard panels such as concentrated photovoltaic systems, heavily soiled or shaded panels or those operating under non-standard spectral illumination; certainly, it is difficult to find such a measurement system that is flexible and affordable enough to be adopted by the smaller research institutes or universities. We present here an instrument aiming to fill this gap, autonomously tracking and maintaining any solar panel at maximum power point while continuously monitoring its operational parameters and dissipating the produced energy without connection to the power grid. The instrument allows periodic acquisition of current-voltage curves to verify the employed maximum power point tracking approach. At the same time, with hardware schematics and software code being provided, it provides a flexible open development environment for the monitoring of non-standard generators like concentrator photovoltaic systems and to test novel power tracking approaches. The key issues, and the corresponding solutions, encountered in the design are analyzed in detail and the relevant schematics presented. PMID- 27250468 TI - New procedure to measure simultaneously the surface tension and contact angle. AB - This paper proposes a new procedure to simultaneously measure the static contact angle and the surface tension of a liquid using a spherical geometry. Unlike the other existing methods, the knowledge of one of both previous parameters and the displacement of the sphere are not mandatory. The technique is based on the measurement of two simple physical quantities: the height of the meniscus formed on a sphere at the very contact with a liquid bath and the resulting vertical force exerted on this object at equilibrium. The meniscus height, whose exact value requires the numerical resolution of the Laplace equation, is often estimated with an approximate 2D model, valid only for very large spheres compared to the capillary length. We develop instead another simplified solution of the Young-Laplace equation based on the work of Ferguson for the meniscus on a cylinder and adapted for the spherical shape. This alternative model, which is less restrictive in terms of the sphere size, is successfully compared to numerical solutions of the complete Young-Laplace equation. It appears to be accurate for sphere radii larger than only two capillary lengths. Finally the feasibility of the method is experimentally tested and validated for three common liquids and two "small" steel spheres. PMID- 27250469 TI - Design and analysis of a high-accuracy flexure hinge. AB - This paper designs and analyzes a new kind of flexure hinge obtained by using a topology optimization approach, namely, a quasi-V-shaped flexure hinge (QVFH). Flexure hinges are formed by three segments: the left and right segments with convex shapes and the middle segment with straight line. According to the results of topology optimization, the curve equations of profiles of the flexure hinges are developed by numerical fitting. The in-plane dimensionless compliance equations of the flexure hinges are derived based on Castigliano's second theorem. The accuracy of rotation, which is denoted by the compliance of the center of rotation that deviates from the midpoint, is derived. The equations for evaluating the maximum stresses are also provided. These dimensionless equations are verified by finite element analysis and experimentation. The analytical results are within 8% uncertainty compared to the finite element analysis results and within 9% uncertainty compared to the experimental measurement data. Compared with the filleted V-shaped flexure hinge, the QVFH has a higher accuracy of rotation and better ability of preserving the center of rotation position but smaller compliance. PMID- 27250470 TI - An absolute instrument for determination of the speed of sound in water. AB - An apparatus for the absolute determination of the sound speed in water based on the time-of-flight technique is described. The time measurement is realized by hardware circuits and the distance measurement by a double-beam plane-mirror interferometer. A highly accurate time chip, with a resolution of approximately 90 ps, is employed for time measurements. The acoustic path length is adjustable and can be measured directly. Two transducers are used for transmitting and receiving ultrasonic signals without reflection. The transducers are immersed in a thermostatic vessel that maintains bath temperature with high stability. The speed of sound in pure water was measured at ambient pressure and at the temperatures 308 K, 303 K, 298 K, and 293 K. The achieved measurement uncertainties are 2 mK for temperature and 0.045 m/s for speed of sound. The results are compared to data from the literature, equation of state models, and measurements by two commercial sensors in the same experiment, showing excellent agreement among them. PMID- 27250471 TI - Force measurement using strain-gauge balance in a shock tunnel with long test duration. AB - Force tests were conducted at the long-duration-test shock tunnel JF12, which has been designed and built in the Institute of Mechanics, Chinese Academy of Sciences. The performance tests demonstrated that this facility is capable of reproducing a flow of dry air at Mach numbers from 5 to 9 at more than 100 ms test duration. Therefore, the traditional internal strain-gauge balance was considered for the force tests use in this large impulse facility. However, when the force tests are conducted in a shock tunnel, the inertial forces lead to low frequency vibrations of the test model and its motion cannot be addressed through digital filtering because a sufficient number of cycles cannot be found during a shock tunnel run. The post-processing of the balance signal thus becomes extremely difficult when an averaging method is employed. Therefore, the force measurement encounters many problems in an impulse facility, particularly for large and heavy models. The objective of the present study is to develop pulse type sting balance by using a strain-gauge sensor that can be applied in the force measurement of 100 ms test time, especially for the force test of the large scale model. Different structures of the S-series (i.e., sting shaped balances) strain-gauge balance are proposed and designed, and the measuring elements are further optimized to overcome the difficulties encountered during the measurement of aerodynamic force in a shock tunnel. In addition, the force tests were conducted using two large-scale test models in JF12 and the S-series strain-gauge balances show good performance in the force measurements during the 100 ms test time. PMID- 27250472 TI - Eddy current-shielded x-space relaxometer for sensitive magnetic nanoparticle characterization. AB - The development of magnetic particle imaging (MPI) has created a need for optimized magnetic nanoparticles. Magnetic particle relaxometry is an excellent tool for characterizing potential tracers for MPI. In this paper, we describe the design and construction of a high-throughput tabletop relaxometer that is able to make sensitive measurements of MPI tracers without the need for a dedicated shield room. PMID- 27250473 TI - A new streaked soft x-ray imager for the National Ignition Facility. AB - A new streaked soft x-ray imager has been designed for use on high energy-density (HED) physics experiments at the National Ignition Facility based at the Lawrence Livermore National Laboratory. This streaked imager uses a slit aperture, single shallow angle reflection from a nickel mirror, and soft x-ray filtering to, when coupled to one of the NIF's x-ray streak cameras, record a 4* magnification, one dimensional image of an x-ray source with a spatial resolution of less than 90 MUm. The energy band pass produced depends upon the filter material used; for the first qualification shots, vanadium and silver-on-titanium filters were used to gate on photon energy ranges of approximately 300-510 eV and 200-400 eV, respectively. A two-channel version of the snout is available for x-ray sources up to 1 mm and a single-channel is available for larger sources up to 3 mm. Both the one and two-channel variants have been qualified on quartz wire and HED physics target shots. PMID- 27250474 TI - Open ISEmeter: An open hardware high-impedance interface for potentiometric detection. AB - In this work, a new open hardware interface based on Arduino to read electromotive force (emf) from potentiometric detectors is presented. The interface has been fully designed with the open code philosophy and all documentation will be accessible on web. The paper describes a comprehensive project including the electronic design, the firmware loaded on Arduino, and the Java-coded graphical user interface to load data in a computer (PC or Mac) for processing. The prototype was tested by measuring the calibration curve of a detector. As detection element, an active poly(vinyl chloride)-based membrane was used, doped with cetyltrimethylammonium dodecylsulphate (CTA(+)-DS(-)). The experimental measures of emf indicate Nernstian behaviour with the CTA(+) content of test solutions, as it was described in the literature, proving the validity of the developed prototype. A comparative analysis of performance was made by using the same chemical detector but changing the measurement instrumentation. PMID- 27250475 TI - An apparatus to measure frictional, anelastic, and viscous behavior in ice at temperate and planetary conditions. AB - In this paper, we describe a cryogenic, servo-controlled biaxial friction apparatus designed to measure the deformational behaviors of ice. The apparatus is specifically designed to accurately achieve and measure the low differential stresses applicable to deforming ice on earth and on icy satellites. We can apply loads in the range ~2-1800 kPa and velocities up to 4 mm/s, with resolution of 39 Pa and 0.7 MUm, respectively. Precise temperature control, measurement, and insulation allow testing at constant temperature (from -2 to -30 degrees C) for prolonged periods of time. The apparatus is tested with various plastics as well as with polycrystalline ice samples and the results are consistent with previously published values. Critical components of the instrument are described along with examples of data collection schemes and preliminary results. The flexibility of the design allows for both glaciological and planetary applications over a range of deformational behaviors including friction, anelastic, and viscous. PMID- 27250476 TI - Note: A novel dielectric barrier discharge system for generating stable patterns in wide range. AB - We develop a novel dielectric barrier discharge (DBD) system with a meshed water electrode to generate stable square superlattice patterns (MSSP) in Ar/air mixture in a wide range of experimental environments. Discharge scenarios with the applied voltage increasing in the meshed DBD and ordinary DBD are presented respectively under the same experimental conditions. It is found that a square pattern and MSSP can be obtained stably and easily in meshed DBD, while no pattern emerges in ordinary DBD. MSSP can be formed when the Ar content is from 0% to 70%, and the corresponding applied voltage decreases with Ar content increasing. Results based on optical methods show that MSSP is generated by artificially designed electrodes together with nonlinear characteristics of DBD, which may account for why patterns in meshed DBD exist in a wide range. PMID- 27250477 TI - Note: Space qualified photon counting detector for laser time transfer with picosecond precision and stability. AB - The laser time transfer link is under construction for the European Space Agency in the frame of Atomic Clock Ensemble in Space. We have developed and tested the flying unit of the photon counting detector optimized for this space mission. The results are summarized in this Note. An extreme challenge was to build a detector package, which is rugged, small and which provides long term detection delay stability on picosecond level. The device passed successfully all the tests required for space missions on the low Earth orbits. The detector is extremely rugged and compact. Its long term detection delay stability is excellent, it is better than +/-1 ps/day, in a sense of time deviation it is better than 0.5 ps for averaging times of 2000 s to several hours. The device is capable to operate in a temperature range of -55 degrees C up to +60 degrees C, the change of the detection delay with temperature is +0.5 ps/K. The device is ready for integration into the space structure now. PMID- 27250478 TI - Note: A portable laser induced breakdown spectroscopy instrument for rapid sampling and analysis of silicon-containing aerosols. AB - A portable instrument has been developed for measuring silicon-containing aerosols in near real-time using laser-induced breakdown spectroscopy (LIBS). The instrument uses a vacuum system to collect and deposit airborne particulate matter onto a translatable reel of filter tape. LIBS is used to analyze the deposited material, determining the amount of silicon-containing compounds present. In laboratory testing with pure silica (SiO2), the correlation between LIBS intensity for a characteristic silicon emission and the concentration of silica in a model aerosol was determined for a range of concentrations, demonstrating the instrument's plausibility for identifying hazardous levels of silicon-containing compounds. PMID- 27250479 TI - Note: The expansion of possibilities for plasma probe diagnostics. AB - The determination of ion mass for low-pressure Maxwellian plasmas has been proposed. It can be done using Langmuir probe measurements and the Bohm formula for the ion current density to a floating probe, due to this formula's reliance on ion mass. This goal was achieved by accurate measurements of xenon plasma parameters in the inductive discharge at pressure p = 2 ? 10(-3) Torr using the Plasma Sensors VGPS-12 probe station with the cylindrical Langmuir probes. The analysis of measurement data showed that in these conditions, the Bohm effect was valid with engineering-level precision, resulting in the experimental Bohm coefficient CBCyl ~ 1.13 for cylindrical probes. PMID- 27250480 TI - Note: Digital laser frequency auto-locking for inter-satellite laser ranging. AB - We present a prototype of a laser frequency auto-locking and re-locking control system designed for laser frequency stabilization in inter-satellite laser ranging system. The controller has been implemented on field programmable gate arrays and programmed with LabVIEW software. The controller allows initial frequency calibrating and lock-in of a free-running laser to a Fabry-Perot cavity. Since it allows automatic recovery from unlocked conditions, benefit derives to automated in-orbit operations. Program design and experimental results are demonstrated. PMID- 27250481 TI - Note: Arc discharge plasma source with plane segmented LaB6 cathode. AB - A plane cathode composed of close-packed hexagonal LaB6 (lanthanum hexaboride) segments is described. The 6 cm diameter circular cathode is heated by radiation from a graphite foil flat spiral. The cathode along with a hollow copper anode is used for the arc discharge plasma production in a newly developed linear plasma device. A separately powered coil located around the anode is used to change the magnetic field strength and geometry in the anode region. Different discharge regimes were realized using this coil. PMID- 27250482 TI - Note: A sub-sampling technique for frequency locking in Doppler wind lidar. AB - Double-edge technique is employed in Doppler wind lidar for detecting the Doppler frequency shift. A dedicated locking channel, employing one channel of a triple Fabry-Perot etalon, is designed to compensate for the effects caused by the frequency drift of outgoing laser. Agilent Oscilloscopes, with a sampling rate of 2.5 GSPS, are employed to obtain accurate amplitudes of the narrow pulses in existing experiments. In order to achieve the requirement of real-time ability and integration, a sub-sampling technique based on the theory of statistics is presented. With the technique, the drift can be acquired at a sub-sampling rate, 250 MSPS. A prototype is designed and the test results show that the prototype, providing real-time ability and better integration, has a comparable performance as the oscilloscope for frequency locking. PMID- 27250483 TI - Note: Design and implementation of a home-built imaging system with low jitter for cold atom experiments. AB - A novel home-built system for imaging cold atom samples is presented using a readily available astronomy camera which has the requisite sensitivity but no timing-control. We integrate the camera with LabVIEW achieving fast, low-jitter imaging with a convenient user-defined interface. We show that our system takes precisely timed millisecond exposures and offers significant improvements in terms of system jitter and readout time over previously reported home-built systems. Our system rivals current commercial "black box" systems in performance and user-friendliness. PMID- 27250484 TI - Note: Development of leg size sensors for fluid accumulation monitoring. AB - A number of diseases can lead to fluid accumulation and swelling in the lower leg. Early detection of leg swelling can be used to effectively predict potential health risks and allows for early intervention from medical providers. Hence this note develops a novel leg size sensor based on the use of magnetic field measurement. An electromagnet is combined with two magnetic field transducers to provide a drift-free leg size estimation technique immune to environmental disturbances. The sensor can measure changes as small as 1 mm in diameter reliably during in vitro tests. Its performance is compared with that of other size measurement techniques. PMID- 27250485 TI - Note: An improved solenoid driver valve for miniature shock tubes. AB - A solenoid driver valve has been built to improve the operating performance of diaphragmless shock tubes, which are used for high pressure, high temperature chemical kinetics, and fluid mechanics studies. For shock tube driver application, the most important characteristics are those of sealing, strength, and quality of the generated shock waves and repeatability of opening characteristics and therefore subsequent post-shock conditions. The main features of the new driver valve are a face o-ring sealing design of the valve, the large internal volume, and through inserts near the solenoid core: adjustable opening characteristics of the valve. PMID- 27250487 TI - Erratum: "Concepts of magnetic filter fields in powerful negative ion sources for fusion" [Rev. Sci. Instrum. 87, 02B315 (2016)]. PMID- 27250488 TI - Publisher's Note: "High sensitivity measurement system for the direct-current, capacitance-voltage, and gate-drain low frequency noise characterization of field effect transistors" [Rev. Sci. Instrum. 87, 044702 (2016)]. PMID- 27250489 TI - [Not Available]. PMID- 27250490 TI - [IL-2-Therapy in SLE- Selective reconstitution of immunological tolerance]. PMID- 27250491 TI - [Inflammation and bone : Osteoimmunological aspects]. AB - Microscopic fractures (so-called microcracks) or traumatic macrofractures require bone, as the basic scaffold of the human body, to have a high regenerative capability. In order to be able to provide this regenerative capability, bone is in a constant process of remodeling. This finely tuned homeostasis of bone formation and degradation can become disrupted, which leads to osteoporosis or other bone disorders. It has been shown that the immune system is substantially involved in the regulation of bone homeostasis and that chronic inflammation in particular can disturb this balance; therefore, this article reviews the osteoimmunological aspects contributing to osteoporosis and other diseases associated with bone degradation. PMID- 27250492 TI - Protective Effects of Selenium, N-Acetylcysteine and Vitamin E Against Acute Ethanol Intoxication in Rats. AB - The aim of this study was to determine possible protective influences of selenium (Se), N-acetylcysteine (NAC), and vitamin E (Vit E) against acute ethanol (EtOH) intoxication. Thirty-six rats were divided into six groups: I (control), II (EtOH), III (EtOH + Se), IV (EtOH + Vit E), V (EtOH + NAC), and VI (EtOH + mix). Except group I, EtOH was given the other pretreated (groups III, IV, V, and VI) and untreated groups (group II). Compared with the EtOH group, serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatine kinase, and creatine kinase-MB levels were significantly decreased in all pretreated groups, whereas slightly diminished amylase and lipase were observed. Compared with the control group, a remarkably lower total antioxidant status (TAS), but higher total oxidant status (TOS), and oxidative stress index (OSI) were seen in brain, liver, and kidney tissues. The values of these parameters were less affected from EtOH-exposed brain tissue of EtOH + NAC and liver of EtOH + mix groups. Both significant decrease of catalase activity and marked increases of adenosine deaminase and myeloperoxidase were determined only in liver tissue of the EtOH group. Activities of these enzymes were restored in almost all pretreated groups. Moreover, an increase of xanthine oxidase activity was prevented in brain tissue of pretreated groups. In histopathological examination of the liver, hydropic degeneration, sinusoidal dilatation, mononuclear cell infiltration, and marked congestion, which were seen in the EtOH group, were prevented in all pretreated groups. Relative protection against acute EtOH toxicity, in both single and combined pretreatments of Se, NAC, and Vit E supplementation, was probably through antioxidant and free radical-neutralizing effects of foregoing materials. PMID- 27250493 TI - Zinc Content in Cord Blood Is Associated with Maternal Age and Parity. AB - At childbirth (parturition), zinc (Zn) homeostasis in cord blood (CB) can be affected by a number of factors: Zn in maternal blood, parturition related stress as well as metallothionein (MT). Both Zn and stress are known inducers of MT which is primarily involved in Zn homeostasis. This study analyzed Zn concentration [Zn], in CB components and MT-2A transcription in CB mononuclear cells (MNC) in relation to primiparous and multiparous childbirth. [Zn] in CB (n = 47) plasma, erythrocytes, and MNCs were measured by atomic absorption spectrophotometry (lambda = 213.9 nm). The MT-2A transcription in CB-MNC was quantified using real-time PCR. Significant correlations (Pearson r) were found between: plasma-[Zn] and erythrocyte-[Zn] (p = 0.002); [Zn] and MT-2A messenger RNA (mRNA) (p = 0.000) in CB-MNC. Student's t tests showed higher levels of MT-2A mRNA and MNC-[Zn] in CB of older (>=25 years) compared to younger mothers (<=24 years) (p = 0.043 and p = 0.016, respectively). Significantly higher [Zn] was found in CB plasma (p = 0.017) and MNC (p = 0.041) of older primiparous compared to the younger primiparous and older multiparous mothers respectively. MT-2A mRNA in CB-MNC was significantly lower in CB of younger primiparous mothers compared to their older counterparts (p = 0.001). Path analysis showed that MNC-[Zn] (beta = 0.83; p = 0.000) had a greater influence on MT-2A mRNA expression, compared to parity (beta = -0.14; p = 0.033). Higher [Zn] in CB of primiparous mothers could be linked to higher stress during parturition, however, might be beneficial for the growth and development of the child. Together MNC-[Zn] and parity contributed ~70 % of the MT-2A transcription in CB-MNC. PMID- 27250494 TI - A Comparative Analysis of the Contents Of Iron, Zinc, Copper, Manganese, and Calcium in the Collective Diet Of Preschool Children in the Northwestern Region of Bosnia. AB - Researches conducted worldwide indicate a frequent deficiency in mineral matters. Due to the increased need during the period of accelerated growth and development, children belong to the group that is exposed to the highest risk of mineral matter deficiency. Our objectives were to determine the iron, zinc, copper, manganese, and calcium intake in the collective diet of the preschool population in the in the northwestern region of Bosnia- in the Republic of Srpska and to estimate the adequacy of the application of the international food composition tables for nutrition planning relating to mineral matters. Samples of food intended for children's diet were collected in the preschool institution "Radost" (a kindergarten), in the city of Prijedor. In daily portions, Fe, Zn, Cu, Mn, and Ca contents were determined by flame atomic absorption spectrophotometry. Contents of mineral matters in daily meals were also calculated by the food composition tables. An average daily meal contained 2.86 mg of Fe, 1.71 mg of Zn, 0.19 mg of Cu, 0.21 mg of Mn, and 83.5 mg of Ca. With calculation method, contents of all minerals are significantly higher than the experimental data for all used food composition tables. The obtained results indicate a significant deficiency in mineral matters in the collective diet of the preschool population in the Republic of Srpska, a certain non-compliance with the applicable recommendations, and also suggest a need to create food composition tables for food being consumed in our region. PMID- 27250495 TI - Blood Selenium Concentration and Blood Cystatin C Concentration in a Randomly Selected Population of Healthy Children Environmentally Exposed to Lead and Cadmium. AB - This study aimed at evaluation of a relationship between blood selenium concentration (Se-B) and blood cystatin C concentration (CST) in a randomly selected population of healthy children, environmentally exposed to lead and cadmium. The studies were conducted on 172 randomly selected children (7.98 +/- 0.97 years). Among participants, the subgroups were distinguished, manifesting marginally low blood selenium concentration (Se-B 40-59 MUg/l), suboptimal blood selenium concentration (Se-B: 60-79 MUg/l) or optimal blood selenium concentration (Se-B >= 80 MUg/l). At the subsequent stage, analogous subgroups of participants were selected separately in groups of children with BMI below median value (BMI <16.48 kg/m2) and in children with BMI >= median value (BMI >=16.48 kg/m2). In all participants, values of Se-B and CST were estimated. In the entire group of examined children no significant differences in mean CST values were detected between groups distinguished on the base of normative Se-B values. Among children with BMI below 16.48 kg/m2, children with marginally low Se-B manifested significantly higher mean CST values, as compared to children with optimum Se-B (0.95 +/- 0.07 vs. 0.82 +/- 0.15 mg/l, p < 0.05). In summary, in a randomly selected population of healthy children no relationships could be detected between blood selenium concentration and blood cystatin C concentration. On the other hand, in children with low body mass index, a negative non-linear relationship was present between blood selenium concentration and blood cystatin C concentration. PMID- 27250496 TI - Assessment of Aflatoxin M1 and Heavy Metal Levels in Mothers Breast Milk in Famagusta, Cyprus. AB - Breast milk contributes towards optimal nutrition for infants. However, studies showed that it can also contain different toxins and heavy metals, which reduce its health benefits. The aim of this study is to determine the level of contaminants such as aflatoxin M1 (AFM1), Pb, Cd, As, and Hg in breast milk samples from Famagusta, Cyprus. Correlations between moldy food consumption, smoking habits of the mothers, and contaminant levels in breast milk were also investigated. Breast milk samples from 50 lactating mothers in rural and urban areas of Famagusta District were analyzed for AFM1 by ELISA. Eighty percent of them were found to be contaminated with AFM1 with the mean measurement of 7.84 +/ 1.72 ng/l. Socio-demographic status, moldy food consumption habits, and smoking status do not have any effect on the AFM1 levels observed in breast milk. Heavy metal levels in breast milk were examined by inductively coupled plasma mass spectrometry, and the mean measurements were1.19 +/- 1.53 ppm for Pb, 0.73 +/- 0.58 ppm for As, 0 +/- 0.20 ppm for Hg, and 0.45 +/- 0.23 ppm for Cd. This study indicates that the levels of these contaminants in breast milk samples obtained in Famagusta District are well within the acceptable levels. However, the presence of AFM1 and heavy metals still may pose risks for infant health. PMID- 27250497 TI - The association between psychosocial and structural-level stressors and HIV injection drug risk behavior among Malaysian fishermen: A cross-sectional study. AB - BACKGROUND: Malaysian fishermen have been identified as a key-affected HIV population with HIV rates 10 times higher than national rates. A number of studies have identified that psychosocial and structural-level stressors increase HIV injection drug risk behaviors. The purpose of this paper is to examine psychosocial and structural-level stressors of injection drug use and HIV injection drug risk behaviors among Malaysian fishermen. METHODS: The study employs a cross-sectional design using respondent driven sampling methods. The sample includes 406 fishermen from Pahang state, Malaysia. Using multivariate logistic regressions, we examined the relationship between individual (depression), social (adverse interactions with the police), and structural (poverty-related) stressors and injection drug use and risky injection drug use (e.g.., receptive and non-receptive needle sharing, frontloading and back loading, or sharing drugs from a common container). RESULTS: Participants below the poverty line had significantly lower odds of injection drug use (OR 0.52, 95 % CI: 0.27-0.99, p = 0.047) and risky injection drug use behavior (OR 0.48, 95 % CI: 0.25-0.93, p = 0.030). In addition, participants with an arrest history had higher odds of injection use (OR 19.58, 95 % CI: 9.81-39.10, p < 0.001) and risky injection drug use (OR 16.25, 95 % CI: 4.73-55.85, p < 0.001). Participants with depression had significantly higher odds of engaging in risky injection drug use behavior (OR 3.26, 95 % 1.39-7.67, p = 0.007). Focusing on participants with a history of injection drug use, we found that participants with depression were significantly more likely to engage in risky drug use compared to participants below the depression cutoff (OR 3.45, 95 % CI: 1.23-9.66, p < 0.02). CONCLUSIONS: Findings underscore the need to address psychosocial and structural-level stressors among Malaysian fishermen to reduce HIV injection drug risk behaviors. PMID- 27250498 TI - Posterior reversible encephalopathy syndrome in a patient with mixed connective tissue disease: a case report. AB - BACKGROUND: Posterior reversible encephalopathy is a syndrome highly associated with hypertension and cytotoxic therapy. The syndrome typically presents with headache, visual abnormality, seizures and characteristic vasogenic edema on magnetic resonance imaging. The entity warrants a prompt diagnosis to avoid deteriorating consequences. CASE PRESENTATION: In this report, we describe a 15 year-old Iranian boy who was diagnosed with mixed connective tissue disease, and cyclophosphamide pulse therapy was administered. Three days after the second pulse of cyclophosphamide, when he was receiving prednisolone and hydroxycholoroquine, our patient developed generalized tonic-clonic seizures. Magnetic resonance imaging findings showed high signal intensities in the posterior areas of his brain. After 8 days, the brain magnetic resonance imaging abnormalities were resolved following the control of his blood pressure and antiepileptic treatment. These observations have been indicative of posterior reversible encephalopathy syndrome. Nevertheless, our patient developed uncontrollable respiratory distress and eventually died. CONCLUSIONS: To the best of our knowledge, this case is the first report of posterior reversible encephalopathy syndrome in a patient with mixed connective tissue disease. As the patient developed posterior reversible encephalopathy syndrome 3 days after cyclophosphamide pulse therapy to reduce the disease activity, it is hard to accurately determine whether posterior reversible encephalopathy syndrome in this case is a complication of cyclophosphamide or a condition that resulted from the mixed connective tissue disease flare-up. PMID- 27250499 TI - Probiotics and microbiota composition. AB - Accumulated evidence, corroborated by a new systematic review by Kristensen et al. (Genome Med 8:52, 2016), suggests that probiotics do not significantly impact the fecal microbiota composition of healthy subjects. Nevertheless, physiological benefits have been associated with probiotic consumption by healthy people. Some studies have suggested that probiotics may impact the function of colonizing microbes, although this needs to be further studied. An alternative hypothesis is that probiotics may promote homeostasis of the gut microbiota, rather than change its composition. This hypothesis warrants investigation as a possible mechanism for how probiotics may benefit healthy people.Please see related article: http://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0300-5 . PMID- 27250500 TI - Deciphering the gene expression profile of peroxisome proliferator-activated receptor signaling pathway in the left atria of patients with mitral regurgitation. AB - BACKGROUND: Differentially expressed genes in the left atria of mitral regurgitation (MR) pigs have been linked to peroxisome proliferator-activated receptor (PPAR) signaling pathway in the KEGG pathway. However, specific genes of the PPAR signaling pathway in the left atria of MR patients have never been explored. METHODS: This study enrolled 15 MR patients with heart failure, 7 patients with aortic valve disease and heart failure, and 6 normal controls. We used PCR assay (84 genes) for PPAR pathway and quantitative RT-PCR to study specific genes of the PPAR pathway in the left atria. RESULTS: Gene expression profiling analysis through PCR assay identified 23 genes to be differentially expressed in the left atria of MR patients compared to normal controls. The expressions of APOA1, ACADM, FABP3, ETFDH, ECH1, CPT1B, CPT2, SLC27A6, ACAA2, SMARCD3, SORBS1, EHHADH, SLC27A1, PPARGC1B, PPARA and CPT1A were significantly up regulated, whereas the expression of PLTP was significantly down-regulated in the MR patients compared to normal controls. The expressions of HMGCS2, ACADM, FABP3, MLYCD, ECH1, ACAA2, EHHADH, CPT1A and PLTP were significantly up-regulated in the MR patients compared to patients with aortic valve disease. Notably, only ACADM, FABP3, ECH1, ACAA2, EHHADH, CPT1A and PLTP of the PPAR pathway were significantly differentially expressed in the MR patients compared to patients with aortic valve disease and normal controls. CONCLUSIONS: Differentially expressed genes of the PPAR pathway have been identified in the left atria of MR patients compared with patients with aortic valve disease and normal controls. PMID- 27250501 TI - Investigation of immunomodulatory and anti-inflammatory effects of eriodictyol through its cellular anti-oxidant activity. AB - Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses against infection or to ameliorate immune-based pathologies. To determine whether eriodictyol has immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we investigated the stimulatory effect of eriodictyol on spleen cells isolated from BALB/c mice. Eriodictyol significantly stimulated splenocyte proliferation. However, only B lymphocytes (not T lymphocytes) could be stimulated by eriodictyol in a dose-related manner. Studies assessing potential effect of eriodictyol on innate immunity reported that eriodictyol enhanced significantly the killing activity of natural killer (NK) cells, T lymphocytes, and macrophages. We also demonstrated that eriodictyol inhibited nitric oxide (NO) production and lysosomal enzyme activity in murine peritoneal macrophages cultured ex-vivo, suggesting a potential anti-inflammatory effect in situ. Eriodictyol revealed also a cellular anti-oxidant activity in splenocytes and macrophages. Furthermore, eriodictyol increased catalase activity in spleen cells. From this data, it can be concluded that eriodictyol exhibited an immunomodulatory effect that could be ascribed in part to a cytoprotective effect related to its anti-oxidant activity. PMID- 27250502 TI - A Multilayer Perceptron Based Smart Pathological Brain Detection System by Fractional Fourier Entropy. AB - This work aims at developing a novel pathological brain detection system (PBDS) to assist neuroradiologists to interpret magnetic resonance (MR) brain images. We simplify this problem as recognizing pathological brains from healthy brains. First, 12 fractional Fourier entropy (FRFE) features were extracted from each brain image. Next, we submit those features to a multi-layer perceptron (MLP) classifier. Two improvements were proposed for MLP. One improvement is the pruning technique that determines the optimal hidden neuron number. We compared three pruning techniques: dynamic pruning (DP), Bayesian detection boundaries (BDB), and Kappa coefficient (KC). The other improvement is to use the adaptive real-coded biogeography-based optimization (ARCBBO) to train the biases and weights of MLP. The experiments showed that the proposed FRFE + KC-MLP + ARCBBO achieved an average accuracy of 99.53 % based on 10 repetitions of K-fold cross validation, which was better than 11 recent PBDS methods. PMID- 27250505 TI - The Proceedings of the 2015 Tohoku Regional Post Graduate Education Meeting. PMID- 27250503 TI - Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow. AB - Complete annotation of the human genome is indispensable for medical research. The GENCODE consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models. However, for both the proteomics and annotation groups, there is a lack of guidelines for integrating this data. Here we report a stringent workflow for the interpretation of proteogenomic data that could be used by the annotation community to interpret novel proteogenomic evidence. Based on reprocessing of three large-scale publicly available human data sets, we show that a conservative approach, using stringent filtering is required to generate valid identifications. Evidence has been found supporting 16 novel protein-coding genes being added to GENCODE. Despite this many peptide identifications in pseudogenes cannot be annotated due to the absence of orthogonal supporting evidence. PMID- 27250506 TI - The Proceedings of the 2015 Tokai-Hokuriku Regional Post Graduate Education Meeting. PMID- 27250504 TI - Deleterious effects of 28-day oral co-administration of first-line anti-TB drugs on spleen, blood and bone marrow chromosomes in normal rat. AB - CONTEXT: Isoniazid, rifampicin and pyrazinamide are most reliable and cost effective remedy for tuberculosis treatment and prophylaxis among first-line anti tuberculosis (TB) drugs and have a pronounced tendency to cause adverse drug reactions. Hepatotoxicity is well-studied side effect of these drugs but their effects on other organs like spleen and blood are still needed to be explored. OBJECTIVE: To explore the probable outcome of co-administration these three major antitubercular drugs (ATDs), rifampicin, isoniazid and pyrazinamide on spleen, blood and bone marrow. MATERIALS AND METHODS: Different parameters were evaluated like lipid peroxidation, glutathione (GSH) and protein content in spleen by spectrophotometric evaluation, hematological evaluation by determining total hemoglobin, total leukocyte count, differential leukocyte count and scanning electron microscopy studies in blood, genotoxicity studied by bone marrow chromosomal analysis and DNA fragmentation. The female rats n = 12 (150-200 g) were grouped as control group orally given saline and toxicant group given INH (30.85 mg/kg b.wt.) + RIF (61.7 mg/kg b.wt.) + PZA (132.65 mg/kg b.wt.) dosage extrapolated from dose that is used in human for 28 d once daily. RESULTS: After 28 d-oral co-administration of anti-TB drugs (INH (30.85 mg/kg b.wt.) + RIF (61.7 mg/kg b.wt.) + PZA (132.65 mg/kg b.wt.)), it was revealed that there were an increase thiobarbituric acid reactive substances, decrease in GSH and protein contents in spleen. Marked changes in hematological parameters, DNA fragmentation and chromosomes were also observed. CONCLUSION: This can be concluded from this work that co-administration of first-line ATDs is toxic to spleen and blood also these drugs can cause damage at genetic level. PMID- 27250507 TI - The Proceedings of the 103th Kinki Regional Meeting of the Japanese Society of Neurology. PMID- 27250510 TI - Editor's Note. PMID- 27250511 TI - Touching the private parts: how gender and sexuality norms affect medical students' first pelvic examination. AB - Gynaecologists are in a position to challenge norms about gender and sexuality in relation to female genitals. Through their work they have the opportunity to educate patients, which is why teaching medical students to perform examinations in a gender sensitive way is significant. Medical students performing their first pelvic examination often experience the examination as uncomfortable because it is a body part that is connected to sex and to something private. This paper uses medical students' interpretations of performing their first pelvic examination as a means to discuss how cultural norms for gender, sexuality and female genitals affect these examinations. Issues raised include how cultural connotations of female genitals affect the pelvic examination, how female and male students relate differently to examining female genitals and the interpretations they make in relation to themselves. Findings show that the female genitals are perceived as a special body part connected to sexuality and intimacy. Students' gender also affects the interpretations they make during pelvic examinations. Norms of gender, sexuality and female genitals need to be challenged in the teaching and performance of pelvic examination in order to demystify this experience. PMID- 27250512 TI - Prospects of chimeric antigen receptor T-cell and natural killer cell therapies in acute leukemias. PMID- 27250513 TI - Update on the surgical management of ovarian neoplasms in children and adolescents: analysis on 32 cases. AB - This study analyzes updated clinical, diagnostic, and surgical directions for the treatment of ovarian neoplasms in children and adolescents, comparing them with a retrospective analysis of 32 cases treated in two Pediatric Surgery University Institutions. From January 2005 to December 2015, 32 pediatric patients were surgically treated for 32 ovarian tumors: 28 (87.5%) benign and 4 (12.5%) malignant neoplastic lesions. Median age at surgery was 11.2 years (12.8 years in patients with benign neoplasms, 7.25 years in patients with malignant ones). All patients with malignant and 25% of patients with benign ovarian lesions had elevated serum level of tumors markers. The surgical approach was laparotomic in 62.5% and laparoscopic in 37.5%; 81.2% surgeries were performed in elective surgery and 18.8% in emergency. Intraoperative frozen section analysis was performed in 18.75% of patients. The most frequent surgery (96.8%) was unilateral oophorectomy. After a median follow-up of 76 months (range 6-132 months), 31/32 patients are alive and disease-free. In case of malignant tumors, fertility sparing surgery with accurate staging must be performed. Laparoscopic multiport is the gold standard approach for benign pediatric ovarian neoplasms, but the use of laparoscopy in full respect of oncological principles also for early stage malignant tumors is currently increased. PMID- 27250515 TI - Synthesis of Mesoporous Single Crystal Co(OH)2 Nanoplate and Its Topotactic Conversion to Dual-Pore Mesoporous Single Crystal Co3O4. AB - A new class of mesoporous single crystalline (MSC) material, Co(OH)2 nanoplates, is synthesized by a soft template method, and it is topotactically converted to dual-pore MSC Co3O4. Most mesoporous materials derived from the soft template method are reported to be amorphous or polycrystallined; however, in our synthesis, Co(OH)2 seeds grow to form single crystals, with amphiphilic block copolymer F127 colloids as the pore producer. The single-crystalline nature of material can be kept during the conversion from Co(OH)2 to Co3O4, and special dual-pore MSC Co3O4 nanoplates can be obtained. As the anode of lithium-ion batteries, such dual-pore MSC Co3O4 nanoplates possess exceedingly high capacity as well as long cyclic performance (730 mAh g(-1) at 1 A g(-1) after the 350th cycle). The superior performance is because of the unique hierarchical mesoporous structure, which could significantly improve Li(+) diffusion kinetics, and the exposed highly active (111) crystal planes are in favor of the conversion reaction in the charge/discharge cycles. PMID- 27250516 TI - Suppression of phase transitions at low temperature by chromium substitution in vanadium spinel Fe(V1-x Cr x )2O4. AB - Synchrotron powder diffraction, magnetization, and specific heat measurements have been used to investigate the structural and magnetic phase transitions in the spinel-type vanadate Fe(V1-x Cr x )2O4 (0.0 ? x ? 1.0). We observed five different transitions in our polycrystalline samples. The canted-type ferrimagnetic phase transition accompanied by the lattice distortion was suppressed by Cr substitution (x = 0.2). Additionally, high-resolution synchrotron powder diffraction revealed that the low-temperature orthorhombic phase appears in FeV2O4 below 30 K and disappears by subtle Cr doping. In contrast, for x ? 0.7, we observed a different magnetic transition of possibly conical-type ferrimagnetic ordering that did not induce significant lattice distortion at the transition temperature. We performed structural refinements for low-temperature phases and suggest that the crystal system of Fe(V1-x Cr x )2O4 at 15K is an orthorhombic lattice for all x values. In the orthorhombic phase, a unique behaviour was observed, with the lattice constants a and b approaching each other as Cr doping increased. This behaviour can be explained by the change of orbitally ordered states of the Fe(2+) ions. PMID- 27250517 TI - Catalyst-controlled switch of regioselectivity in the asymmetric allylic alkylation of oxazolones with MBHCs. AB - A catalyst-controlled switch of regioselectivity in asymmetric allylic alkylation of oxazolones with MBHCs was described. The SN2'-SN2' reaction catalysed by a quinine-derived base produced gamma-selective secondary allylic oxazolone derivatives, whereas the addition-elimination reaction catalysed by an amino acid derived bifunctional urea catalyst provided beta-selective primary adducts. PMID- 27250518 TI - [Reporting occupational disease in the Valencia Autonomous Community]. PMID- 27250519 TI - [Archivos, much accomplished, much left to do]. PMID- 27250520 TI - [Work-related motor vehicle injuries among workers at a banking institution (2007 2013)]. AB - OBJECTIVE: To study physical harm caused by road accidents (LATT in Spanish) among employees of a Spanish financial institution from 2007 to 2013. Additionally, we tried to define damage features in each sex and at different ages in hurt patients, as well as work disability caused by this type of injury. METHODS: Cross-sectional study of labor injuries verified by the occupational medical service of the bank. Absolute (n) and relative (%) frequencies related to interesting variables were described. Chi-square test was used to assess correlation. RESULTS: Along the mentioned period of time, 1.517 traumatic occupational injuries were recorded on a population of 14.541 workers. 27% of them were LATT. 1,3% of these were fatal or seriously harmful, significantly associated to sex and age (p < 0,05). Co-driver damage, LATT in itinere and twist or sprain were more common in women. LATT at work and closed fractures were more frequent in men.Work disability caused by LATT was higher than other traumatic occupational injuries. CONCLUSIONS: LATT in the studied sample were almost three times higher than LATT are among general Spanish population, but serious lesions in our group were less common.We observed differences in LATT distribution by sexes and ages in workers included in this study, and also a higher incidence of work disability compared to the whole traumatic occupational injuries. Public health and occupational health authorities must find efficient strategies in order to diminish the incidence of these LATT-associated injuries. PMID- 27250521 TI - [Work-related common mental disorders in Navarra, Spain (2009-2012)]. AB - OBJECTIVES: To determine work-related mental health morbidity and correct psychosocial risks. METHODOLOGY: In this pilot study conducted at a mental health center, work-related common mental disorders were identified and population incidence was estimated.We next described cases reported from primary care centers in the period 2009 to 2012, via the Occupational Health Surveillance Program. Incidence was calculated by socioeconomic variables. Associations among variables (Chi2 test), their prevalence ratios (PR) and the correlation of risks (kappa coefficient) were compared. Reporting of these cases to the occupational health services and subsequent actions are described. RESULTS: In the pilot study, 17.5% of common mental disorders were work-related (7.2 x 1000 workers / year). Among the reported cases, incidence was higher in unskilled occupations, feminized economic activities and the services sector. Seventy per cent of cases were associated with hostile behavior and 14.2% with organizational factors. In addition, 83.2% of cases led to sickness absence episodes. Managing directors were at greater risk of bullying (PR 3.92 95%CI 2.35-6.53) as compared to other risks. Overall, 20% of cases ended in job dismissal, particularly in cases of mistreatment or bullying (PR 1.64 95%CI 1.24-2.16). CONCLUSIONS: It is necessary to implement reporting systems and prevention programs for work-relaed mental disorders, especially for collectives of workers with high risk profiles. PMID- 27250522 TI - [Scrotal cancer: the first occupational cancer]. PMID- 27250524 TI - Neuroprotective effects of the ethanol stem bark extracts of Terminalia ivorensis in ketamine-induced schizophrenia-like behaviors and oxidative damage in mice. AB - CONTEXT: Schizophrenia is a heterogenous neurological disorder, which has been hypothetically linked to oxidative imbalance and associated behavioral perturbations. Preliminary evidence from animal models predictive of human psychosis suggests that Terminalia ivorensis A. Chev. (Combretaceae) has antipsychotic-like activity in mice. OBJECTIVE: This study investigates the neuroprotective property of the ethanol stem bark extracts of T. ivorensis (EETI) in reversal treatment of ketamine-induced schizophrenia-like behaviors and oxidative alteration in adult male Swiss albino mice. MATERIALS AND METHODS: Animals were divided into six treatment groups (n = 5). Animals received distilled water or ketamine (20 mg/kg) once daily intraperitoneally (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with EETI (125, 250 or 500 mg/kg), risperidone (RIS) or vehicle orally once daily. Behaviors related to positive (locomotor activity) and cognitive (Y maze) symptoms of schizophrenia were assessed. Glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, including malondialdehyde (MDA) concentration were measured in mice whole brains. RESULT: The LD50 of EETI was 2236.06 mg/kg, p.o. body weight. EETI (125, 250 or 500 mg/kg, p.o.) demonstrated significant (p < 0.05) inhibition of ketamine-induced hyperlocomotion and cognitive dysfunction. The extract decreased MDA concentration (39.0, 62.6 and 67.5%) in a dose-dependent manner. Moreover, EETI significantly (p < 0.05) reversed the depletion of GSH, and increased activities of SOD and CAT in brain tissues. DISCUSSION AND CONCLUSION: These findings suggest that EETI probably exert its antipsychotic-like activity, via a neuroprotective compensatory mechanism of action, and as such, could be relevant in the management of schizophrenia. PMID- 27250523 TI - Estrogen/ERR-alpha signaling axis is associated with fiber-type conversion of upper airway muscles in patients with obstructive sleep apnea hypopnea syndrome. AB - Estrogen is related with the low morbidity associated with obstructive sleep apnea hypopnea syndrome (OSAS) in women, but the underlying mechanisms remain largely unknown. In this study, we examined the relationship between OSAS and estrogen related receptor-alpha (ERR-alpha). We found that the expression levels of ERR-alpha and Myh7 were both downregulated in palatopharyngeal tissues from OSAS patients. In addition, we report that ERR-alpha is dynamically expressed during differentiation of C2C12 myoblasts. Knockdown of ERR-alpha via instant siRNA resulted in reduced expression of Myh7, but not Myh4. Furthermore, differentiation of C2C12 cells under 3% chronic intermittent hypoxia, a model resembling human OSAS, was impaired and accompanied by a obvious reduction in Myh7 expression levels. Moreover, activation of ERR-alpha with 17beta-estradiol (E2) increased the expression of Myh7, whereas pretreatment with the ERR-alpha antagonist XCT790 reversed the E2-induced slow fiber-type switch. A rat ovariectomy model also demonstrated the switch to fast fiber type. Collectively, our findings suggest that ERR-alpha is involved in estrogen-mediated OSAS by regulating Myhc-slow expression. The present study illustrates an important role of the estrogen/ERR-alpha axis in the pathogenesis of OSAS, and may represent an attractive therapeutic target, especially in postmenopausal women. PMID- 27250525 TI - Direct observation of polar tweed in LaAlO3. AB - Polar tweed was discovered in mechanically stressed LaAlO3. Local patches of strained material (diameter ca. 5 MUm) form interwoven patterns seen in birefringence images, Piezo-Force Microscopy (PFM) and Resonant Piezoelectric Spectroscopy (RPS). PFM and RPS observations prove unequivocally that electrical polarity exists inside the tweed patterns of LaAlO3. The local piezoelectric effect varies greatly within the tweed patterns and reaches magnitudes similar to quartz. The patterns were mapped by the shift of the Eg soft-mode frequency by Raman spectroscopy. PMID- 27250526 TI - Thiazolides Elicit Anti-Viral Innate Immunity and Reduce HIV Replication. AB - Nitazoxanide (Alinia((r)), NTZ) and tizoxanide (TIZ), its active circulating metabolite, belong to a class of agents known as thiazolides (TZD) endowed with broad anti-infective activities. TIZ and RM-4848, the active metabolite of RM 5038, were shown to stimulate innate immunity in vitro. Because natural resistance to HIV-1 infection in HIV-exposed seronegative (HESN) individuals is suggested to be associated with strong innate immune responses, we verified whether TIZ and RM-4848 could reduce the in vitro infectiousness of HIV-1. Peripheral blood mononuclear cells (PBMCs) from 20 healthy donors were infected in vitro with HIV-1BaL in the presence/absence of TIZ or RM4848. HIV-1 p24 were measured at different timepoints. The immunomodulatory abilities of TZD were evaluated by the expression of type I IFN pathway genes and the production of cytokines and chemokines. TZD drastically inhibited in vitro HIV-1 replication (>87%). This was associated with the activation of innate immune responses and with the up-regulation of several interferon-stimulated genes (ISGs), including those involved in cholesterol pathway, particularly the cholesterol-25 hydroxylase (CH25H). TZD inhibition of HIV-1 replication in vitro could be due to their ability to stimulate potent and multifaceted antiviral immune responses. These data warrant the exploration of TZD as preventive/therapeutic agent in HIV infection. PMID- 27250527 TI - Collaborative care for anxiety disorders in primary care: a systematic review and meta-analysis. AB - BACKGROUND: Studies evaluating collaborative care for anxiety disorders are recently emerging. A systematic review and meta-analysis to estimate the effect of collaborative care for adult patients with anxiety disorders in primary care is therefore warranted. METHODS: A literature search was performed. DATA SOURCES: PubMed, Psycinfo, Embase, Cinahl, and the Cochrane library. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials examining the effects of collaborative care for adult primary care patients with an anxiety disorder, compared to care as usual or another intervention. Synthesis methods: Standardized mean differences (SMD) on an anxiety scale closest to twelve months follow-up were calculated and pooled in a random effects meta-analysis. RESULTS: Of the 3073 studies found, seven studies were included with a total of 2105 participants. Included studies were of moderate to high quality. Collaborative care was superior to care as usual, with a small effect size (SMD = 0.35 95 % CI 0.14 0.56) for all anxiety disorders combined and a moderate effect size (SMD = 0.59, 95 % CI 0.41-0.78) in a subgroup analysis (five studies) on patients with panic disorder. CONCLUSIONS: Collaborative care seems to be a promising strategy for improving primary care for anxiety disorders, in particular panic disorder. However, the number of studies is still small and further research is needed to evaluate the effectiveness in other anxiety disorders. PMID- 27250528 TI - Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis. AB - BACKGROUND: Abundant evidence from epidemiological and clinical studies has proven that diabetes mellitus (DM) is correlated with an increased incidence of dementia and Alzheimer's disease (AD). Insulin resistance is considered to play an important role in the associations between DM and dementia. However, whether insulin sensitizer drugs are effective in preventing dementia still remains unclear. METHODS: Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies that reported about the associations between insulin sensitizers and the incidence of dementia. The included studies were reviewed, and a meta-analysis was performed using STATA to determine the combined relative risk (RR) for the incidence of dementia when using insulin sensitizers. Subgroup analysis and meta regression were also conducted. RESULTS: In total, nine comparisons out of six studies were qualified for inclusion, and data from 544,093 participants were evaluated. The results of the meta-analysis revealed a combined RR of 0.78 (95% CI 0.64-0.95, p = 0.015) for the incidence of dementia when using insulin sensitizers. The incidence rate of dementia was reduced with either metformin (RR 0.79, 95% CI 0.62-1.01, p = 0.064) or thiazolidinediones (RR 0.75, 95% CI 0.56-1.00, p = 0.050), both with a marginal trend toward significance. CONCLUSIONS: The results indicate that insulin sensitizer drugs might provide protection against incident dementia. Controlled studies with large samples should be conducted to further confirm these conclusions and provide information for clinical strategies. PMID- 27250529 TI - A nanofiber based artificial electronic skin with high pressure sensitivity and 3D conformability. AB - Pressure sensors with 3D conformability are highly desirable components for artificial electronic skin or e-textiles that can mimic natural skin, especially for application in real-time monitoring of human physiological signals. Here, a nanofiber based electronic skin with ultra-high pressure sensitivity and 3D conformability is designed and built by interlocking two elastic patterned nanofibrous membranes. The patterned membrane is facilely prepared by casting conductive nanofiber ink into a silicon mould to form an array of semi-spheroid like protuberances. The protuberances composed of intertwined elastic POE nanofibers and PPy@PVA-co-PE nanofibers afford a tunable effective elastic modulus that is capable of capturing varied strains and stresses, thereby contributing to a high sensitivity for pressure sensing. This electronic skin like sensor demonstrates an ultra-high sensitivity (1.24 kPa(-1)) below 150 Pa with a detection limit as low as about 1.3 Pa. The pixelated sensor array and a RGB-LED light are then assembled into a circuit and show a feasibility for visual detection of spatial pressure. Furthermore, a nanofiber based proof-of-concept wireless pressure sensor with a bluetooth module as a signal transmitter is proposed and has demonstrated great promise for wireless monitoring of human physiological signals, indicating a potential for large scale wearable electronic devices or e-skin. PMID- 27250530 TI - Drop formation using ferrofluids driven magnetically in a step emulsification device. AB - We present a microfluidic droplet generation technique, where instead of pumps, only magnetic field gradient strength adjusted by the position of an external magnet is used for controllable emulsification of ferrofluid containing solutions. Uniform droplet generation at frequencies O(1-100) Hz per channel for long periods of time (10s of minutes) were easily achieved. In this method, adding magnetic nanoparticles (10 nm) into aqueous solutions imparts a magnetic body force on the fluid in the presence of an external magnetic field gradient. Consequently, the aqueous fluid moves toward the position of an external magnet and towards a junction with a larger width and height oil filled reservoir. Emulsification occurs at the junction due to a rapid change in surface tension forces due to the abrupt change in channel height. Droplet generation rate could be controlled by adjusting surface tension/viscosity, number of channels, and strength of the magnetic force. The geometry of the channel, rather than flow rates or magnetic force, plays the dominant role in defining the droplet size. In addition, reagents mixed with ferrofluids could also be introduced from two or more separate inlets and mixed prior to emulsification as they move toward the step driven by magnetic force. Mixing reagents on chip and forming droplets all within a small foot-print defined by movement of an external magnet is a unique feature of this method suitable for point-of-care diagnostics and other bioengineering applications. PMID- 27250532 TI - Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation. AB - Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA) induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-alpha and IL-6 production in endothelial cells by specifically suppressing IKKbeta/NF-kappabeta phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings. PMID- 27250533 TI - Increased concentration of 8-hydroxy-2'-deoxyguanosine in follicular fluid of infertile women with endometriosis. AB - Impaired oocyte quality and oxidative stress might be involved in the pathogenesis of endometriosis-related infertility. To improve our understanding of the role of oxidative stress in this condition, we compare eight oxidative stress markers from each stage, including the simultaneous analysis of lipids, proteins and DNA damage, in the serum and follicular fluid of infertile women with endometriosis and infertile controls undergoing controlled ovarian stimulation for intracytoplasmic sperm injection. In total, 87 serum samples (43 with endometriosis, 44 controls) and 61 follicular fluid samples (29 with endometriosis, 32 controls) free of blood contamination upon visual inspection and presenting granulosa cells alone or granulosa cells plus a retrieved mature oocyte were collected on the day of oocyte retrieval. Total hydroperoxides, malondialdehyde, advanced oxidation protein products, glutathione, superoxide dismutase (SOD) and total antioxidant capacity (TAC) were determined by spectrophotometry, vitamin E by high-performance liquid chromatography and 8 hydroxy-2'-deoxyguanosine (8OHdG) by enzyme-linked immunosorbent assay. The endometriosis group showed higher serum concentrations of glutathione and SOD, lower serum concentrations of TAC and higher follicular concentrations of 8OHdG and vitamin E compared with infertile controls. These data indicate both systemic and follicular oxidative stress in infertile patients with endometriosis. For the first time, we demonstrate the presence of oxidative DNA damage, represented by higher 8OHdG concentrations in the follicular microenvironment of these patients, possibly related to compromised oocyte quality and associated with the pathogenesis of endometriosis-related infertility. PMID- 27250535 TI - Neoantigen activation, protein translocation and targeted drug delivery in combination with radiotherapy. AB - Concurrent chemo and radiation therapies are commonly used to treat locally advanced cancer. Despite improved efficacy, failure rates remain high due to healthy organ toxicity caused by chemo-radiotherapy. Recent technological advances such as nanoparticle encapsulation of anticancer agents, locally controlled irradiation and concurrent use of radio- and nano-medicines are providing innovative solutions for overcoming the limitations of systemic and local treatment toxicities. In this mini-review, we discuss the roles of radiotherapy in generating new therapeutic targets and altering the tumor microenvironment, and we propose their future applications in drug delivery in combination with radiotherapy. PMID- 27250536 TI - Design, modification and in vitro evaluation of pectin's bucco-adhesiveness. AB - AIM: It was the aim of this study to synthesize pectin (PEC) with sulfhydryl groups and evaluate its suitability in buccal application. MATERIALS & METHODS: Native PEC was chemically modified by covalent attachment of sulfhydryl-bearing cysteine (CYS). Stability assays in form of water uptake behavior and erosion study were performed. Additionally, mucoadhesive study on buccal mucosa was performed. RESULTS: Pectin-cysteine (PECCYS) was successfully synthesized as proved by IR and Ellman's assay exhibiting 436.59 +/- 127.87 umol thiol groups per gram polymer. Stability assay showed that PECCYS revealed a 2.27-fold improved water uptake and mucoadhesiveness augmented 3.75-fold in comparison to unmodified PEC. CONCLUSION: PECCYS might be a future suitable excipient for buccal adhesive application. PMID- 27250534 TI - Quantifying intrinsic and extrinsic control of single-cell fates in cancer and stem/progenitor cell pedigrees with competing risks analysis. AB - The molecular control of cell fate and behaviour is a central theme in biology. Inherent heterogeneity within cell populations requires that control of cell fate is studied at the single-cell level. Time-lapse imaging and single-cell tracking are powerful technologies for acquiring cell lifetime data, allowing quantification of how cell-intrinsic and extrinsic factors control single-cell fates over time. However, cell lifetime data contain complex features. Competing cell fates, censoring, and the possible inter-dependence of competing fates, currently present challenges to modelling cell lifetime data. Thus far such features are largely ignored, resulting in loss of data and introducing a source of bias. Here we show that competing risks and concordance statistics, previously applied to clinical data and the study of genetic influences on life events in twins, respectively, can be used to quantify intrinsic and extrinsic control of single-cell fates. Using these statistics we demonstrate that 1) breast cancer cell fate after chemotherapy is dependent on p53 genotype; 2) granulocyte macrophage progenitors and their differentiated progeny have concordant fates; and 3) cytokines promote self-renewal of cardiac mesenchymal stem cells by symmetric divisions. Therefore, competing risks and concordance statistics provide a robust and unbiased approach for evaluating hypotheses at the single cell level. PMID- 27250539 TI - What is the future of noninvasive routes for protein- and peptide-based drugs? PMID- 27250538 TI - Injectable thermosensitive gelling delivery system for the sustained release of lidocaine. AB - BACKGROUND: Patients undergoing arthroplasty require appropriate postsurgical pain relief. Analgesia is typically achieved through bolus doses of short-acting local anesthetics and with oral analgesics such as opiates, which are associated with systemic side effects. By formulating an injectable thermosensitive gelling system containing lidocaine, sustained and local delivery can be achieved following a single administration. RESULTS: Poloxamer-based thermosensitive gelling formulations were prepared. Altering the weight ratios of poloxamers affected the sol-to-gel transition temperature, mechanical and rheological properties and in vitro drug release. Desirable formulations gelled between 28 and 33 degrees C providing sustained release of lidocaine over 48 h. CONCLUSION: Thermosensitive gelling systems are promising for sustained drug release following patient administration and may be beneficial in addressing postoperative pain. PMID- 27250540 TI - Lineage-specific chromatin signatures reveal a regulator of lipid metabolism in microalgae. AB - Alga-derived lipids represent an attractive potential source of biofuels. However, lipid accumulation in algae is a stress response tightly coupled to growth arrest, thereby imposing a major limitation on productivity. To identify transcriptional regulators of lipid accumulation, we performed an integrative chromatin signature and transcriptomic analysis to decipher the regulation of lipid biosynthesis in the alga Chlamydomonas reinhardtii. Genome-wide histone modification profiling revealed remarkable differences in functional chromatin states between the algae and higher eukaryotes and uncovered regulatory components at the core of lipid accumulation pathways. We identified the transcription factor, PSR1, as a pivotal switch that triggers cytosolic lipid accumulation. Dissection of the PSR1-induced lipid profiles corroborates its role in coordinating multiple lipid-inducing stress responses. The comprehensive maps of functional chromatin signatures in a major clade of eukaryotic life and the discovery of a transcriptional regulator of algal lipid metabolism will facilitate targeted engineering strategies to mediate high lipid production in microalgae. PMID- 27250537 TI - In pursuit of functional electrospun materials for clinical applications in humans. AB - Electrospinning is a simple, low-cost and versatile approach to fabricate multifunctional materials useful in drug delivery and tissue engineering applications. Despite its emergence into other manufacturing sectors, electrospinning has not yet made a transformative impact in the clinic with a pharmaceutical product for use in humans. Why is this the current state of electrospun materials in biomedicine? Is it because electrospun materials are not yet capable of overcoming the biological safety and efficacy challenges needed in pharmaceutical products? Or, is it that technological advances in the electrospinning process are needed? This review investigates the current state of electrospun materials in medicine to identify both scientific and technological gaps that may limit clinical translation. PMID- 27250541 TI - A vesicle-trafficking protein commandeers Kv channel voltage sensors for voltage dependent secretion. AB - Growth in plants depends on ion transport for osmotic solute uptake and secretory membrane trafficking to deliver material for wall remodelling and cell expansion. The coordination of these processes lies at the heart of the question, unresolved for more than a century, of how plants regulate cell volume and turgor. Here we report that the SNARE protein SYP121 (SYR1/PEN1), which mediates vesicle fusion at the Arabidopsis plasma membrane, binds the voltage sensor domains (VSDs) of K(+) channels to confer a voltage dependence on secretory traffic in parallel with K(+) uptake. VSD binding enhances secretion in vivo subject to voltage, and mutations affecting VSD conformation alter binding and secretion in parallel with channel gating, net K(+) concentration, osmotic content and growth. These results demonstrate a new and unexpected mechanism for secretory control, in which a subset of plant SNAREs commandeer K(+) channel VSDs to coordinate membrane trafficking with K(+) uptake for growth. PMID- 27250542 TI - Phosphorus nutrition in Proteaceae and beyond. AB - Proteaceae in southwestern Australia have evolved on some of the most phosphorus impoverished soils in the world. They exhibit a range of traits that allow them to both acquire and utilize phosphorus highly efficiently. This is in stark contrast with many model plants such as Arabidopsis thaliana and crop species, which evolved on soils where nitrogen is the major limiting nutrient. When exposed to low phosphorus availability, these plants typically exhibit phosphorus starvation responses, whereas Proteaceae do not. This Review explores the traits that account for the very high efficiency of acquisition and use of phosphorus in Proteaceae, and explores which of these traits are promising for improving the phosphorus efficiency of crop plants. PMID- 27250543 TI - The non-processive rice kinesin-14 OsKCH1 transports actin filaments along microtubules with two distinct velocities. AB - Microtubules and actin filaments function coordinately in many cellular processes(1-3). Although much of this coordination is mediated by proteins that statically bridge the two cytoskeletal networks(4-6), kinesin-14 motors with an actin binding calponin homology domain (KCHs) have been discovered as putatively dynamic crosslinkers in plants(7,8). OsKCH1, a KCH from rice, interacts with both microtubules and actin filaments in vivo and in vitro(9). However, it has remained unclear whether this interaction is dynamic or if actin binding reduces or even abolishes the motor's motility on microtubules(10,11). Here, we directly show in vitro that OsKCH1 is a non-processive, minus-end-directed motor that transports actin filaments along microtubules. Interestingly, we observe two distinct transport velocities dependent on the relative orientation of the actin filaments with respect to the microtubules. In addition, torsional compliance measurements on individual molecules reveal low flexibility in OsKCH1. We suggest that the orientation-dependent transport velocities emerge from OsKCH1's low torsional compliance combined with an inherently oriented binding to the actin filament. Together, our results imply a central role of OsKCH1 in the polar orientation of actin filaments along microtubules, and thus a contribution to the organization of the cytoskeletal architecture. PMID- 27250544 TI - Rice genetics: Control of grain length and quality. PMID- 27250545 TI - Growth and development: Close relations of secretion and K(.). PMID- 27250546 TI - Evolutionary outcomes should inform strategies to increase drought tolerance. PMID- 27250547 TI - Signal transduction: GABA receptor found in plants. PMID- 27250548 TI - The hidden half of crop yields. PMID- 27250550 TI - Rose scent: Restricting methane. PMID- 27250549 TI - Achieving more crop per drop. PMID- 27250551 TI - Invasive species: Trading places. PMID- 27250553 TI - Auxin signalling: Ancestral pathways. PMID- 27250552 TI - Rice agriculture: Restricting methane. PMID- 27250554 TI - Better than riches. PMID- 27250555 TI - Vcfanno: fast, flexible annotation of genetic variants. AB - The integration of genome annotations is critical to the identification of genetic variants that are relevant to studies of disease or other traits. However, comprehensive variant annotation with diverse file formats is difficult with existing methods. Here we describe vcfanno, which flexibly extracts and summarizes attributes from multiple annotation files and integrates the annotations within the INFO column of the original VCF file. By leveraging a parallel "chromosome sweeping" algorithm, we demonstrate substantial performance gains by annotating ~85,000 variants per second with 50 attributes from 17 commonly used genome annotation resources. Vcfanno is available at https://github.com/brentp/vcfanno under the MIT license. PMID- 27250556 TI - Inlay osteotome sinus floor elevation with concentrated growth factor application and simultaneous short implant placement in severely atrophic maxilla. AB - Sinus floor elevation with simultaneous implant placement in severely atrophic maxilla is challenging. The aim of this retrospective study was to evaluate the short-term performance of modified osteotome sinus floor elevation (OSFE) with concentrated growth factor (CGF) application and concurrent placement of a short implant in cases with residual bone height (RBH) of 2-4 mm. Twenty-five short implants were installed in 16 patients with mean RBH of 3.23 mm using modified OSFE with CGFs from January 2012 to April 2014. Postoperatively, the implants were clinically evaluated, and vertical bone gain (VBG) was measured using cone beam computed tomography. The mean duration of follow-up was 19.88 months (12-32 months). All the implants were stable with an overall survival rate of 100%. The mean VBG immediately after surgery was 9.21 mm. Six months later, significant reduction of alveolar bone height (2.90 +/- 0.22 mm) was found (P < 0.05). During the second 6-month period, further alveolar bone resorption (0.14 +/- 0.11 mm) was noted but without significance (P > 0.05). Within the limits of this study, modified OSFE with CGF application and simultaneous short implant placement could yield predictable clinical results for severely atrophic maxilla with RBH of 2-4 mm. PMID- 27250557 TI - Oxygen Saturation Targets for Extremely Preterm Infants after the NeOProM Trials. AB - Five randomized controlled trials comparing lower (85-89%) versus higher (91-95%) pulse oximeter saturation (SpO2) targets for extremely preterm infants have now been reported from the United States of America, Canada, the United Kingdom, Australia and New Zealand. These trials included more than 4,800 infants, and they provide robust evidence to permit comparison of these target ranges and consider the next steps for clinicians and researchers. The lower SpO2 range was associated with a significant increase in the risk of death. There was no significant difference between the two target ranges in the rate of disability at 18-24 months, including blindness. A significant difference between groups in the risk of the composite primary outcome of death or disability in favour of the higher SpO2 range was mainly attributable to the difference between groups in the risk of death. The lower target range did not reduce bronchopulmonary dysplasia or severe visual impairment, but it did increase the risk of necrotizing enterocolitis requiring surgery or causing death. The trials provide no reason to prefer SpO2 targets below 90% and indicate the importance of more trials to see if a further survival advantage can be identified. The safety of targets above 95% has not been evaluated. The five trials were designed to be similar to facilitate an individual patient data meta-analysis, and this Neonatal Oxygen Prospective Meta-Analysis (NeOProM) may provide further insights. PMID- 27250559 TI - Fatty Acids and Bioactive Lipids of Potato Cultivars: An Overview. AB - Potato tuber is a highly nutritious, wherein genotype and environmental differences are known to exist in the shape, size and nutritional value of potatoes. Owing to its high consumption, potato could be an ideal carrier of health-promoting phytochemicals. Potato cultivars contain many bioactive lipidic compounds such as fatty acids, glycolipids, phospholipids, sterols, tocols and carotenoids, which are highly desirable in diet because of their health-promoting effects. In the scientific literature, information on the content and profile of bioactive lipidic compounds in potato cultivars are few. The concentration and stability of bioactive lipids are affected by many factors such as genotype, agronomic factors, postharvest storage, cooking and processing conditions. In this review levels and composition of bioactive lipids in terms of lipid classes, fatty acids, phytosterols, tocopherols, and caroteinoids distribution in different potato cultivars including genetically modified potato (GMP) were highlighted and discussed. In addition, factors affecting bioactive lipids levels, stability and health benefits are reviewed. In consideration of potential nutritional value, detailed knowledge on lipids of potato cultivars is of major importance. PMID- 27250558 TI - Sphere-forming cells from peripheral cornea demonstrate the ability to repopulate the ocular surface. AB - BACKGROUND: The limbus forms the outer rim of the cornea at the corneoscleral junction and harbours a population of stem cells for corneal maintenance. Injuries to the limbus, through disease or accidents such as chemical injuries or burns, may lead to significant visual impairment due to depletion of the native stem cells of the tissue. METHODS: Sphere-forming cells were isolated from peripheral cornea for potential use as transplantable elements for limbal stem cell repopulation and limbal reconstruction. Immunocytochemistry, live cell imaging and quantitative PCR were used to characterize spheres and elucidate activity post implantation into human cadaveric corneal tissue. RESULTS: Spheres stained positively for stem cell markers ?NP63alpha, ABCG2 and ABCB5 as well as the basal limbal marker and putative niche marker, notch 1. In addition, spheres also stained positively for markers of corneal cells, vimentin, keratin 3, keratocan and laminin, indicating a heterogeneous mix of stromal and epithelial origin cells. Upon implantation into decellularized corneoscleral tissue, 3D, polarized and radially orientated cell migration with cell proliferation was observed. Cells migrated out from the spheres and repopulated the entire corneal surface over 14 days. Post-implantation analysis revealed qualitative evidence of stem, stromal and epithelial cell markers while quantitative PCR showed a quantitative reduction in keratocan and laminin expression indicative of an enhanced progenitor cell response. Proliferation, quantified by PCNA expression, significantly increased at 4 days subsequently followed by a decrease at day 7 post implantation. CONCLUSION: These observations suggest great promise for the potential of peripheral corneal spheres as transplantable units for corneal repair, targeting ocular surface regeneration and stem cell repopulation. PMID- 27250560 TI - Characteristics and Composition of a High Oil Yielding Castor Variety from Pakistan. AB - Keeping in view the versatile applications of castor oil in cosmetic, pharmaceutical and recently as renewable source, the present work is a step towards the commercialization of castor on large scale in Pakistan. The current study introduces a castor variety with high oil content. Initially seeds were physically examined for some physical parameters. Seed moisture, ash content and linear dimensions such as length, width and thickness were found to be 4.53%, 6.44%, 12.24 mm, 8.31 mm and 5.67 mm, respectively. For oil extraction, Soxhlet method was used which resulted in the high oil content 54.0%. For quality assessment of oil, physicochemical parameters were checked according to official standard AOCS methods and compared with ASTM specifications. The determined parameters were as follows; specific gravity 0.953 g/cm(-3), refractive index 1.431, viscosity 672.0 mPas.s, moisture content 0.32%, FFA 0.14%, IV 83.61 gI2/100 g, PV 2.25 meq/Kg and SV 186.0 mgKOH/g. Furthermore, fatty acid analysis of oil showed that, most abundant fatty acid was ricinoleic acid 94.59%, followed by palmitic 0.31%, linoleic 1.84%, oleic (n-9) 2.05%, oleic (n-10) 0.22%, stearic 0.45% and eicosenoic acid 0.53%. The detected fatty acids were compared with registered variety and varieties of other regions. PMID- 27250563 TI - Comparison of two automated mononuclear cell collection systems in patients undergoing extracorporeal photopheresis: a prospective crossover equivalence study. AB - BACKGROUND: Extracorporeal photopheresis (ECP) is an effective cell therapy employed in several diseases, including graft versus host disease (GVHD) and organ rejection. When ECP is performed using an off-line technique, mononuclear cell (MNC) collection by leukapheresis is necessary for further manipulation (addition of 8-methoxypsoralen and ultraviolet A irradiation before reinfusion to the patient). We report the results of the first crossover equivalence study on yield and purity of MNCs collected from patients undergoing ECP with two different automated systems: MNC and CMNC (working with intermittent and continuous-flow collection, respectively), released by Terumo BCT. STUDY DESIGN AND METHODS: Fifty-one patients (15 males and 36 females) with GVHD or chronic lung allograft dysfunction were consecutively enrolled and randomly assigned to MNC collection alternatively by the CMNC or MNC system within each ECP cycle (two procedures) in two consecutive cycles. ECP procedures were performed using the off-line technique, according to our internal protocol, processing 1.5 blood volumes. RESULTS: A total of 204 ECP procedures were evaluated. The MNC system showed a higher MNC concentration capacity than the CMNC (mean difference, 13.46; 95% confidence interval, -21.05 to -5.47; p < 0.001). Collection efficiency was higher with the CMNC system as well as total MNC bag content, while MNC bag purity was equivalent for both systems. Platelet loss was higher with the CMNC. Equivalence was shown for MNC purity and anticoagulant infused to the patient. CONCLUSION: CMNC and MNC systems offer different advantages in different clinical conditions, and both are safe and efficient in collecting MNCs for ECP. PMID- 27250562 TI - Artemisinin-based antimalarial research: application of biotechnology to the production of artemisinin, its mode of action, and the mechanism of resistance of Plasmodium parasites. AB - Malaria is a worldwide disease caused by Plasmodium parasites. A sesquiterpene endoperoxide artemisinin isolated from Artemisia annua was discovered and has been accepted for its use in artemisinin-based combinatorial therapies, as the most effective current antimalarial treatment. However, the quantity of this compound produced from the A. annua plant is very low, and the availability of artemisinin is insufficient to treat all infected patients. In addition, the emergence of artemisinin-resistant Plasmodium has been reported recently. Several techniques have been applied to enhance artemisinin availability, and studies related to its mode of action and the mechanism of resistance of malaria-causing parasites are ongoing. In this review, we summarize the application of modern technologies to improve the production of artemisinin, including our ongoing research on artemisinin biosynthetic genes in other Artemisia species. The current understanding of the mode of action of artemisinin as well as the mechanism of resistance against this compound in Plasmodium parasites is also presented. Finally, the current situation of malaria infection and the future direction of antimalarial drug development are discussed. PMID- 27250565 TI - Development of Metal-Organic Framework for Gaseous Plant Hormone Encapsulation To Manage Ripening of Climacteric Produce. AB - Controlled ripening of climacteric fruits, such as bananas and avocados, is a critical step to provide consumers with high-quality products while reducing postharvest losses. Prior to ripening, these fruits can be stored for an extended period of time but are usually not suitable for consumption. However, once ripening is initiated, they undergo irreversible changes that lead to rapid quality loss and decay if not consumed within a short window of time. Therefore, technologies to slow the ripening process after its onset or to stimulate ripening immediately before consumption are in high demand. In this study, we developed a solid porous metal-organic framework (MOF) to encapsulate gaseous ethylene for subsequent release. We evaluated the feasibility of this technology for on-demand stimulated ripening of bananas and avocados. Copper terephthalate (CuTPA) MOF was synthesized via a solvothermal method and loaded with ethylene gas. Its crystalline structure and chemical composition were characterized by X ray diffraction crystallography, porosity by N2 and ethylene isotherms, and morphology by electron microscopy. The MOF loaded with ethylene (MOF-ethylene) was placed inside sealed containers with preclimacteric bananas and avocados and stored at 16 degrees C. The headspace gas composition and fruit color and texture were monitored periodically. Results showed that this CuTPA MOF is highly porous, with a total pore volume of 0.39 cm(3)/g. A 50 mg portion of MOF-ethylene can absorb and release up to 654 MUL/L of ethylene in a 4 L container. MOF ethylene significantly accelerated the ripening-related color and firmness changes of treated bananas and avocados. This result suggests that MOF-ethylene technology could be used for postharvest application to stimulate ripening just before the point of consumption. PMID- 27250564 TI - Death in the intestinal epithelium-basic biology and implications for inflammatory bowel disease. AB - Every 4-5 days, intestinal epithelial cells (IEC) are terminated as they reach the end of their life. This process ensures that the epithelium is comprised of the fittest cells that maintain an impermeable barrier to luminal contents and the gut microbiota, as well as the most metabolically able cells that conduct functions in nutrient absorption, digestion, and secretion of antimicrobial peptides. IEC are terminated by apical extrusion-or shedding-from the intestinal epithelial monolayer into the gut lumen. Whether death by apoptosis signals extrusion or death follows expulsion by younger IEC has been a matter of debate. Seemingly a minor detail, IEC death before or after apical extrusion bears weight on the potential contribution of apoptotic IEC to intestinal homeostasis as a consequence of their recognition by intestinal lamina propria phagocytes. In inflammatory bowel disease (IBD), excessive death is observed in the ileal and colonic epithelium. The precise mode of IEC death in IBD is not defined. A highly inflammatory milieu within the intestinal lamina propria, rich in the proinflammatory cytokine, TNF-alpha, increases IEC shedding and compromises barrier integrity fueling more inflammation. A milestone in the treatment of IBD, anti-TNF-alpha therapy, may promote mucosal healing by reversing increased and inflammation-associated IEC death. Understanding the biology and consequences of cell death in the intestinal epithelium is critical to the design of new avenues for IBD therapy. PMID- 27250567 TI - Early regression of coronary artery remodeling with esmolol and DDAH/ADMA pathway in hypertensive rats. AB - Our preclinical study demonstrated that esmolol produces early regression of left ventricular hypertrophy in arterial hypertension. The aim of this study was to assess the effects of short-term esmolol therapy on the regression of left anterior descending artery remodeling in spontaneously hypertensive rats (SHRs), and to determine whether the asymmetric dimethylarginine (ADMA)/dimethylarginine dimethylaminohydrolase (DDAH) pathway, a regulator of nitric oxide (NO) bioavailability, accounted for this regression. Fourteen-month-old male SHRs were treated intravenously with vehicle (SHR, n=15) or esmolol (SHR-E, n=20) (300 MUg kg-1 min-1). Age-matched, vehicle-treated male Wistar-Kyoto rats (WKY, n=15) served as controls. SHRs were also treated with nitroglycerin (SHR-N, n=5). After 48 h, the left anterior descending artery structure and morphology were assessed, and dose-response curves for 5-hydroxytryptamine (5-HT, 10-9-3 * 10-5 mol l-1) were constructed. ADMA concentrations in plasma and left ventricle and DDAH activity in tissue were analyzed. Wall thickness and cross-sectional area were significantly lower after treatment with esmolol in SHR-E than in SHR. Media thickness and smooth muscle cell count were lower in SHR-E than in SHR. Esmolol induced a significant reduction in adventitial cell count in SHR-E. The area under the concentration-response curves was significantly higher in SHR than in SHR-E, as were the esmolol normalized coronary artery contracting responses to 5 HT. We found significantly lower ADMA levels and significantly higher DDAH activity in the ventricle in SHR-E than in SHR. The protective effect of esmolol on the regression of left anterior descending artery remodeling may be related to the reduction in ADMA levels. PMID- 27250568 TI - Effects of smoking and its cessation on creatinine- and cystatin C-based estimated glomerular filtration rates and albuminuria in male patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry. AB - Cigarette smoking is an important modifiable risk factor for lifestyle diseases. The smoking rate remains high, and the prevalence of diabetes mellitus is increasing in Asian countries; however, few studies have examined the effects of smoking on chronic kidney disease (CKD) in Asian diabetic patients. The aim of the present study was to investigate the association between smoking and its cessation with CKD and its components in patients with type 2 diabetes. A total of 2770 Japanese male patients with type 2 diabetes aged ?20 years were divided according to the amount of cigarette smoking and the years since cessation. The associations with CKD, the urinary albumin-creatinine ratio (UACR) and the estimated glomerular filtration rate (eGFR) were cross-sectionally examined. The proportions of CKD and the mean UACR dose-dependently increased with increases in both the number of cigarettes per day and the Brinkman index compared with the never smokers. The creatinine-based eGFR also increased with increases in the amount of smoking, whereas the cystatin C-based eGFR decreased, and their average did not significantly change. These parameters exhibited inverse associations with the years after smoking cessation compared with the association with the amount of smoking. A dose-dependent association of active smoking and a graded inverse association of the years since quitting with CKD enhance the merit of smoking cessation in patients with type 2 diabetes. PMID- 27250566 TI - Enhancer of Zeste Homolog 2 and Histone Deacetylase 9c Regulate Age-Dependent Mesenchymal Stem Cell Differentiation into Osteoblasts and Adipocytes. AB - Mesenchymal stem cells (MSCs) are multipotent precursors that can undergo multilineage differentiation, including osteogenesis and adipogenesis, which are two mutually exclusive events. Previously, we demonstrated that enhancer of zeste homolog 2 (EZH2), the catalytic component of the Polycomb-repressive complex 2, mediates epigenetic silencing of histone deacetylase 9c (HDAC9c) in adipocytes but not in osteoblasts and that HDAC9c accelerates osteogenesis while attenuating adipogenesis of MSCs through inactivation of peroxisome proliferator-activated receptor gamma 2 activity. Importantly, disrupting the balance between adipogenesis and osteogenesis can lead to age-associated bone loss (osteoporosis) and obesity. Here, we investigated the relationship between age, and osteogenic and adipogenic differentiation potential of MSCs by comparing EZH2 and HDAC9c expression in osteoblasts and adipocytes of both human and mice origins to determine whether the EZH2-HDAC9c axis regulates age-associated osteoporosis and obesity. Our findings indicated that a decline in HDAC9c expression over time was accompanied by increased EZH2 expression and suggested that a therapeutic intervention for age-associated osteoporosis and obesity may be feasible by targeting the EZH2-HDAC9c axis. Stem Cells 2016;34:2183-2193. PMID- 27250569 TI - Comparing para-rowing set-ups on an ergometer using kinematic movement patterns of able-bodied rowers. AB - While numerous studies have investigated the biomechanics of able-bodied rowing, few studies have been completed with para-rowing set-ups. The purpose of this research was to provide benchmark data for handle kinetics and joint kinematics for able-bodied athletes rowing in para- rowing set-ups on an indoor ergometer. Able-bodied varsity rowers performed maximal trials in three para-rowing set-ups; Legs, Trunk and Arms (LTA), Trunk and Arms (TA) and Arms and Shoulders (AS) rowing. The handle force kinetics of the LTA stroke were comparable to the values for able-bodied literature. Lumbar flexion at the catch, extension at the finish and total range of motion were, however, greater than values in the literature for able-bodied athletes in the LTA set-up. Additionally, rowers in TA and AS set ups utilised more extreme ranges of motion for lumbar flexion, elbow flexion and shoulder abduction than the LTA set-up. This study provides the first biomechanical values of the para-rowing strokes for researchers, coaches and athletes to use while promoting the safest training programmes possible for para rowing. PMID- 27250570 TI - Demonstration of a positron beam-driven hollow channel plasma wakefield accelerator. AB - Plasma wakefield accelerators have been used to accelerate electron and positron particle beams with gradients that are orders of magnitude larger than those achieved in conventional accelerators. In addition to being accelerated by the plasma wakefield, the beam particles also experience strong transverse forces that may disrupt the beam quality. Hollow plasma channels have been proposed as a technique for generating accelerating fields without transverse forces. Here we demonstrate a method for creating an extended hollow plasma channel and measure the wakefields created by an ultrarelativistic positron beam as it propagates through the channel. The plasma channel is created by directing a high-intensity laser pulse with a spatially modulated profile into lithium vapour, which results in an annular region of ionization. A peak decelerating field of 230 MeV m(-1) is inferred from changes in the beam energy spectrum, in good agreement with theory and particle-in-cell simulations. PMID- 27250571 TI - Clinical features and management of 33 patients with 46,XX pure gonadal dysgenesis. AB - The objective of the study is to summarize the clinical characteristics of 33 patients' cohort (46,XX pure gonadal dysgenesis, 46,XX PGD), discuss the management, and propose treatment suggestions. Patients' information, medical history, and medical records were obtained. All patients were closely followed up. At the time of diagnosis, the patients presented 19.53 +/- 3.60 years old, 165 +/- 6.49 cm height, breast development of Tanner stage I, and infantile female genitalia. High level of follicle-stimulating hormone (87.41 +/- 21.50 mIU/mL) and LH (27.10 +/- 8.47 mIU/mL) and low level of E2 (8.85 +/- 6.13 pg/mL) were observed. Individualized hormone replacement therapy (HRT) was initiated after diagnosis. After 2 years of treatment, all patients had obvious breast development; the uterus showed (2.38 +/- 0.60) * (1.38 +/- 0.70) * (1.38 +/- 0.55) cm growth. The incidence of osteopenia changed from 69.70% to 22.22% and that of osteoporosis changed from 18.18% to 0. Dysgeminoma was found in one patient. We concluded that gonadal dysgenesis in 46,XX PGD causes secondary sexual characteristic absence, tendency of taller, osteoporosis, infertility, and sexual health problems. There is minor chance of tumor occurrence for the patients. Optimal care including HRT and close follow-up are required. PMID- 27250572 TI - Identification of Regulatory DNA Elements Using Genome-wide Mapping of DNase I Hypersensitive Sites during Tomato Fruit Development. AB - Development and ripening of tomato fruit are precisely controlled by transcriptional regulation, which depends on the orchestrated accessibility of regulatory proteins to promoters and other cis-regulatory DNA elements. This accessibility and its effect on gene expression play a major role in defining the developmental process. To understand the regulatory mechanism and functional elements modulating morphological and anatomical changes during fruit development, we generated genome-wide high-resolution maps of DNase I hypersensitive sites (DHSs) from the fruit tissues of the tomato cultivar "Moneymaker" at 20 days post anthesis as well as break stage. By exploring variation of DHSs across fruit development stages, we pinpointed the most likely hypersensitive sites related to development-specific genes. By detecting binding motifs on DHSs of these development-specific genes or genes in the ascorbic acid biosynthetic pathway, we revealed the common regulatory elements contributing to coordinating gene transcription of plant ripening and specialized metabolic pathways. Our results contribute to a better understanding of the regulatory dynamics of genes involved in tomato fruit development and ripening. PMID- 27250573 TI - Interaction of Heterotrimeric G-Protein Components with Receptor-like Kinases in Plants: An Alternative to the Established Signaling Paradigm? PMID- 27250574 TI - Forty years of yeast genome exploration by Bernard Dujon. PMID- 27250575 TI - Verbal Dominant Memory Impairment and Low Risk for Post-operative Memory Worsening in Both Left and Right Temporal Lobe Epilepsy Associated with Hippocampal Sclerosis. AB - Post-operative memory changes after temporal lobe surgery have been established mainly by group analysis of cognitive outcome. This study investigated individual patient-based memory outcome in surgically-treated patients with mesial temporal lobe epilepsy (TLE). This study included 84 consecutive patients with intractable TLE caused by unilateral hippocampal sclerosis (HS) who underwent epilepsy surgery (47 females, 41 left [Lt] TLE). Memory functions were evaluated with the Wechsler Memory Scale-Revised before and at 1 year after surgery. Pre-operative memory function was classified into three patterns: verbal dominant memory impairment (Verb-D), visual dominant impairment (Vis-D), and no material-specific impairment. Post-operative changes in verbal and visual memory indices were classified into meaningful improvement, worsening, or no significant changes. Pre operative patterns and post-operative changes in verbal and visual memory function were compared between the Lt and right (Rt) TLE groups. Pre-operatively, Verb-D was the most common type of impairment in both the Lt and Rt TLE groups (65.9 and 48.8%), and verbal memory indices were lower than visual memory indices, especially in the Lt compared with Rt TLE group. Vis-D was observed only in 11.6% of Rt and 7.3% of Lt TLE patients. Post-operatively, meaningful improvement of memory indices was observed in 23.3-36.6% of the patients, and the memory improvement was equivalent between Lt and Rt TLE groups and between verbal and visual materials. In conclusion, Verb-D is most commonly observed in patients with both the Lt and Rt TLE associated with HS. Hippocampectomy can improve memory indices in such patients regardless of the side of surgery and the function impaired. PMID- 27250576 TI - Boron Neutron Capture Therapy for Malignant Brain Tumors. AB - Boron neutron capture therapy (BNCT) is a biochemically targeted radiotherapy based on the nuclear capture and fission reactions that occur when non radioactive boron-10, which is a constituent of natural elemental boron, is irradiated with low energy thermal neutrons to yield high linear energy transfer alpha particles and recoiling lithium-7 nuclei. Therefore, BNCT enables the application of a high dose of particle radiation selectively to tumor cells in which boron-10 compound has been accumulated. We applied BNCT using nuclear reactors for 167 cases of malignant brain tumors, including recurrent malignant gliomas, newly diagnosed malignant gliomas, and recurrent high-grade meningiomas from January 2002 to May 2014. Here, we review the principle and history of BNCT. In addition, we introduce fluoride-18-labeled boronophenylalanine positron emission tomography and the clinical results of BNCT for the above-mentioned malignant brain tumors. Finally, we discuss the recent development of accelerators producing epithermal neutron beams. This development could provide an alternative to the current use of specially modified nuclear reactors as a neutron source, and could allow BNCT to be performed in a hospital setting. PMID- 27250577 TI - Usefulness of positron emission tomographic studies for gliomas. AB - Non-invasive positron emission tomography (PET) enables the measurement of metabolic and molecular processes with high sensitivity. PET plays a significant role in the diagnosis, prognosis, and treatment of brain tumors and predominantly detects brain tumors by detecting their metabolic alterations, including energy metabolism, amino acids, nucleic acids, and hypoxia. Glucose metabolic tracers are related to tumor cell energy and exhibit good sensitivity but poor specificity for malignant tumors. Amino acid metabolic tracers provide a better delineation of tumors and cellular proliferation. Nucleic acid metabolic tracers have a high sensitivity for malignant tumors and cellular proliferation. Hypoxic metabolism tracers are useful for detecting resistance to radiotherapy and chemotherapy. Therefore, PET imaging techniques are useful for detecting biopsy targeting points, deciding on tumor resection, radiotherapy planning, monitoring therapy, and distinguishing brain tumor recurrence or progression from post radiotherapy effects. However, it is not possible to use only one PET tracer to make all clinical decisions because each tracer has both advantages and disadvantages. This study focuses on the different kinds of PET tracers and summarizes their recent applications in patients with gliomas. Combinational uses of PET tracers are expected to contribute to differential diagnosis, prognosis, treatment targeting, and monitoring therapy. PMID- 27250580 TI - Gastric carcinosarcoma with rhabdomyosarcomatous differentiation: a case report and review. AB - We report an unusual case of gastric carcinosarcoma with rhabdomyosarcomatous and neudoendocrinal differentiation in a 71-year-old Japanese female. Gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation is a rare tumor. The tumor developed in the body of the stomach and was exophytic in appearance. By histochemical analysis, the tumor was shown a part of positive for desmin and myoglobin and a part of positive for synaphtophysin and vimentin.We conclude that, though rare, gastric carcinosarcoma with rhabdomyosarcomatous and neuroendocrinal differentiation thus is reviewed in the English literatures. PMID- 27250579 TI - Biallelic CACNA1A mutations cause early onset epileptic encephalopathy with progressive cerebral, cerebellar, and optic nerve atrophy. AB - The CACNA1A gene encodes the transmembrane pore-forming alpha-1A subunit of the Cav 2.1 P/Q-type voltage-gated calcium channel. Several heterozygous mutations within this gene, including nonsense mutations, missense mutations, and expansion of cytosine-adenine-guanine repeats, are known to cause three allelic autosomal dominant conditions-episodic ataxia type 2, familial hemiplegic migraine type 1, and spinocerebellar ataxia type 6. An association with epilepsy and CACNA1A mutations has also been described. However, the link with epileptic encephalopathies has emerged only recently. Here we describe two patients, sister and brother, with compound heterozygous mutations in CACNA1A. Exome sequencing detected biallelic mutations in CACNA1A: A missense mutation c.4315T>A (p.Trp1439Arg) in exon 27, and a seven base pair deletion c.472_478delGCCTTCC (p.Ala158Thrfs*6) in exon 3. Both patients were normal at birth, but developed daily recurrent seizures in early infancy with concomitant extreme muscular hypotonia, hypokinesia, and global developmental delay. The brain MRI images showed progressive cerebral, cerebellar, and optic nerve atrophy. At the age of 5, both patients were blind and bedridden with a profound developmental delay. The elder sister died at that age. Their parents and two siblings were heterozygotes for one of those pathogenic mutations and expressed a milder phenotype. Both of them have intellectual disability and in addition the mother has adult onset cerebellar ataxia with a slowly progressive cerebellar atrophy. Compound heterozygous mutations in the CACNA1A gene presumably cause early onset epileptic encephalopathy, and progressive cerebral, cerebellar and optic nerve atrophy with reduced lifespan. (c) 2016 Wiley Periodicals, Inc. PMID- 27250581 TI - Quantitative antibody-free LC-MS/MS analysis of sTRAIL in sputum and saliva at the sub-ng/mL level. AB - Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) induces apoptosis via the extrinsic death receptor pathway and may be a biomarker in the pathogenesis of a broad range of diseases. To investigate the role of sTRAIL in asthma, we developed a quantitative LC-MS/MS method with a lower limit of quantitation (LLOQ) of ~3pM in induced sputum (174pg/mL) and saliva (198pg/mL) without the use of antibodies. sTRAIL was enriched by immobilized metal affinity chromatography (IMAC) solid-phase extraction (SPE) followed by tryptic digestion and subsequent enrichment of a signature peptide by strong cation exchange (SCX) SPE. The method was validated with respect to stability, accuracy and precision using the standard addition approach and fully metabolically (15)N-labelled hrTRAIL as internal standard. Our results indicate that it is possible to quantify cytokines like sTRAIL at the pM level by LC-MS/MS without the use of antibodies, which has, to our knowledge, never been shown before. PMID- 27250583 TI - Multifocal and refractory pyoderma gangrenosum: Possible role of cocaine abuse. AB - Pyoderma gangrenosum is a rare and severe inflammatory skin condition. There are different variants, including generalised and atypical forms, but the most common presentation is an enlarging ulcer on the lower extremities. Treatment can represent a challenge for physicians and there are no guidelines based on randomised controlled trials. We report an exceptional case of widespread and refractory pyoderma gangrenosum in a middle-aged woman where cocaine use may have played a role. Treatment with i.v. pulse corticosteroids and cyclosporine was ineffective, and disease control was obtained with oral corticosteroids together with mycophenolic acid, infliximab and abstinence from cocaine consumption. There was a temporal relationship between disease outbreaks and cocaine consumption and improvement after its discontinuation. In the present case such clinical severity without associated pathology and the temporal association with cocaine abuse raises the possibility of cocaine playing an aetiological role as well as accounting for therapy resistance. PMID- 27250584 TI - Pseudoaneurysmal defect of mitral-aortic intervalvular fibrosa is likely to be a cerebral embolic source. An autopsy study in remote period from the stroke. PMID- 27250582 TI - Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice. AB - We previously reported that LXR ligand, T0901317, inhibited the growth of inoculated Lewis lung carcinoma in C57BL/6 mice by activating IFN-gamma production. However, the effects of T0901317 on carcinogen-induced pulmonary carcinomas remain unknown. In this study, we initially conducted a statistical analysis on the data of human lung cancer samples extracted from the TCGA database, and determined that survival rate/time of lung cancer patients and grade of lung adenocarcinoma were positively and negatively related to lung IFN gamma levels, respectively. We then determined the inhibitory effects of T0901317 on mouse pulmonary carcinomas induced by 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) or urethane. We found that T0901317 reduced morbidity and mortality in MCA/BHT-injected BALB/c mice by inhibiting lung adenocarcinoma. T0901317 also protected C57BL/6 mice, but not IFN-gamma deficient (IFN-gamma(-/ ), C57BL/6 background) mice, against MCA/BHT-induced lung hyperplasia/inflammation. In addition, we determined that T0901317 inhibited urethane-induced lung tumors in BABL/c mice. Furthermore, we determined that T0901317 prevented metastasis of 4T1 breast cancer cells in BALB/c mice. Administration of T0901317 substantially increased serum IFN-gamma levels and lung IFN-gamma expression in BABL/c and C57BL/6 mice. Taken together, our study demonstrates that LXR inhibits MCA/BHT-induced pulmonary carcinomas in BABL/c mice and the inhibition is associated with induction of IFN-gamma production. PMID- 27250585 TI - Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia. AB - To gain insight into the origin and clinical significance of leukocytes that lack human leukocyte antigen A (HLA-A) allele expression caused by a copy-number neutral loss of heterozygosity in the short arm of chromosome 6 in patients with acquired aplastic anemia (AA), we used a high-sensitivity flow cytometry assay to investigate the presence of HLA-A allele-lacking leukocytes (HLA-LLs) in 144 AA patients. HLA-LLs, accounting for 0.2-99.8% of each leukocyte population, were detected in 18 of 71 (25.4%) newly diagnosed patients and in 25 of 73 (34.2%) previously treated patients. The lineage combination patterns of the HLA-LLs in the 43 HLA-LL(+) patients were granulocytes (Gs), monocytes (Ms), B cells (Bs), and T cells (Ts; GMBT) in 13 cases, GMB in 16 cases, GM in 11 cases, and B alone in three cases. The response rate to antithymocyte globulin plus cyclosporine therapy (100%) and the 2-year, failure-free survival rate (100%) in 8 newly diagnosed HLA-LL(+) patients were significantly higher than in 23 HLA-LL(-) patients (52.2% for both). These data suggest that HLA-LLs are a useful marker of the presence of immune pathophysiology in AA and that T-cell attacks against hematopoietic progenitor cells, rather than against hematopoietic stem cells, can trigger bone marrow failure in AA patients. PMID- 27250586 TI - Identification of pigmented Serratia marcescens symbiotically associated with Rhynchophorus ferrugineus Olivier (Coleoptera: Curculionidae). AB - To characterize red pigment-producing bacteria (RPPB) regularly released during oviposition by red palm weevil (RPW), RPPB were recovered from eggs deposited in apples supplied as substrate for oviposition. The presence of RPPB was also detected from gut, the reproductive apparatus of dissected adult and virgin insects and from pupal cases collected within infested palms. RPPB were also identified all along the tissue of these palms. Analysis of the 16S rDNA, gyrB, rpoB, recA, and groEL sequences assigned RPPB to the species Serratia marcescens. RPPB exhibited an antimicrobial activity assessed by the agar well diffusion method against a number of gram-positive and gram-negative bacteria. In this study, we first report the identification of a red pigment-producing S. marcescens as extracellular symbiont of RPW. Route of transmission, detection within different organs, and a wide spread along the infested palm tissue, suggested S. marcescens is present as extracellular symbiont in different developmental stages of the RPW. Additionally, the antimicrobial activity exhibited versus Bacillus spp., Paenibacillus spp., and Lysinibacillus spp., reported as insect pathogens and potential candidates for biocontrol agents, could ascribe for S. marcescens a potential protective role. PMID- 27250588 TI - Letter: oral low-dose methotrexate for collagenous colitis. PMID- 27250589 TI - Letter: oral low-dose methotrexate for collagenous colitis - authors' reply. PMID- 27250590 TI - Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis. PMID- 27250591 TI - Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis - authors' reply. PMID- 27250592 TI - Letter: a simple out-patient faecal microbiota transplant technique. PMID- 27250593 TI - Letter: anti-TNF in steroid-dependent ulcerative colitis - are the available data enough? PMID- 27250594 TI - Chromogenic Detection of Aqueous Formaldehyde Using Functionalized Silica Nanoparticles. AB - Silica nanoparticles functionalized with thiol reactive units and bulky polar polyamines were used for the selective colorimetric detection of formaldehyde. The reaction of thiols groups in the nanoparticles surface with a squaraine dye resulted in loss of the pi-conjugation of the chromophores, and the subsequent bleaching of the solution. However, when formaldehyde was present in the suspension, the thiol-squaraine reaction was inhibited and a chromogenic response was observed. A selective response to formaldehyde was observed only when the thiol and polyamine groups were anchored to the silica surface. The observed selective response was ascribed to the fact that bulky polyamines generate a highly polar environment around thiols, which were only able to react with the small and polar formaldehyde, but not with other aldehydes. The sensing nanoparticles showed a limit of detection (LOD) for formaldehyde of 36 ppb in water. PMID- 27250595 TI - Sequential bottom-up and top-down processing for the synthesis of transition metal dichalcogenide nanosheets: the case of rhenium disulfide (ReS2). AB - Bottom-up (aerosol-assisted chemical vapor deposition, AACVD) and top-down (liquid phase exfoliation, LPE) processing methodologies are used in tandem to produce colloids of few-layer thick rhenium disulfide (ReS2) in N-methyl pyrrolidone. The processing route we use is a potentially robust and scalable pathway to manufacture useful 2D materials. PMID- 27250596 TI - Faculty Mentors' Perspectives on E-Mentoring Post-Professional Occupational Therapy Doctoral Students. AB - E-mentoring is a viable option for mentoring students in occupational therapy educational programs. The objective of this study was to investigate faculty perspectives of faculty-to-student e-mentoring in an online post-professional doctor of occupational therapy program. In a retrospective mixed-method design, nine faculty members described features and outcomes of e-mentoring 48 doctoral students. Online survey results were analysed quantitatively for descriptive statistics; transcripts from structured interviews were analysed using qualitative content analysis. The results showed that successful, satisfactory e mentoring is student-centered, flexible, frequent, academically and psychosocially supportive; faculty members must be skilled in adapting e mentoring to the needs and objectives of each mentee; e-mentoring provides opportunities for faculty members and students to achieve academic and professional objectives and growth. The findings suggest that implementation of e mentoring may be a useful model in other occupational therapy programs. There is a need for future studies with broader participant pool, observable measures of e mentoring, standardized measures of satisfaction and success and comparison between e-mentoring with and without web camera. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27250597 TI - Is it time for everolimus-based combination in castration-resistant prostate cancer? PMID- 27250598 TI - IRAK1 variant is protective for orthodontic-induced external apical root resorption. AB - OBJECTIVE: Interleukin-1 beta (IL1B) pathway is a key player in orthodontic induced external apical root resorption (EARR). The aim of this work was to identify the genes related to the IL1 pathway as possible candidate genes for EARR, which might be included in an integrative predictive model of this complex phenotype. MATERIALS AND METHODS: Using a stepwise multiple linear regression model, 195 patients who had undergone orthodontic treatment were assessed for clinical and genetic factors associated with %EARRmax (maximum %EARR value obtained for each patient). The four maxillary incisors and the two maxillary canines were assessed. Three functional single nucleotide polymorphisms (SNPs) were genotyped: rs1143634 in IL1B gene, rs315952 in IL1RN gene, and rs1059703 in X-linked IRAK1 gene. RESULTS: The model showed that four of the nine clinical variables and one SNP explained 30% of the %EARRmax variability. The most significant unique contributions to the model were gender (P = 0.001), treatment duration (P < 0.001), premolar extractions (P = 0.003), Hyrax appliance (P < 0.001), and homozygosity/hemizygosity for variant C from IRAK1 gene (P = 0.018), which proved to be a protective factor. CONCLUSION: IRAK1 polymorphism is proposed as a protective variant for EARR. PMID- 27250599 TI - A rare variant between the left superior vena cava and the azygos vein. AB - During the educational dissection of a 68-year-old Chinese male cadaver, an azygos vein (AV) coursing on the left side with double superior vena cava was observed. The left superior vena cava (LSVC) began from the confluence of the left internal jugular and left subclavian veins, and extended downwards medially into the left edge of the dilated coronary sinus. The right superior vena cava was formed by the union of the right internal jugular and right subclavian veins, and drained into the right atrium from the above. The AV was formed by the union of the right and left ascending lumbar veins at the level of the tenth thoracic vertebra. It ascended along the left margin of the thoracic vertebra, receiving almost the bilateral posterior intercostal veins and then extended into the LSVC on the left wall via the azygos arch. Better understanding of these variations will reduce unnecessary and potential harmful testing, and unneeded patient anxiety. PMID- 27250600 TI - The ecology of sex explains patterns of helping in arthropod societies. AB - Across arthropod societies, sib-rearing (e.g. nursing or nest defence) may be provided by females, by males or by both sexes. According to Hamilton's 'haplodiploidy hypothesis', this diversity reflects the relatedness consequences of diploid vs. haplodiploid inheritance. However, an alternative 'preadaptation hypothesis' instead emphasises an interplay of ecology and the co-option of ancestral, sexually dimorphic traits for sib-rearing. The preadaptation hypothesis has recently received empirical support, but remains to be formalised. Here, we mathematically model the coevolution of sex-specific helping and sex allocation, contrasting these hypotheses. We find that ploidy per se has little effect. Rather, the ecology of sex shapes patterns of helping: sex-specific preadaptation strongly influences who helps; a freely adjustable sex ratio magnifies sex biases and promotes helping; and sib-mating, promiscuity, and reproductive autonomy also modulate the sex and abundance of helpers. An empirical survey reveals that patterns of sex-specific helping in arthropod taxa are consistent with the preadaptation hypothesis. PMID- 27250601 TI - [Effective bowel preparation before coloscopy - low-volume PEG in the divided dose regimen]. AB - INTRODUCTION: The good and safe bowel cleansing is key to the success of coloscopy. The standard preparation involves 4 l polyethylene glycol (PEG). Now the combination of PEG and ascorbic acid (PEGA) of half the volume is available. Besides the type of product also the time factors which are not clarified, play a role during the bowel preparation. The aim of the study was to compare the efficiency and tolerance of both the agents and evaluate the effect of the time regimen of preparation. METHODS: 380 individuals were included in the evaluation in 4 cohorts which used 4 l PEG (Fortrans) in a single dose or split into 3 + 1 l and PEG + ascorbic acid (Moviprep) split into 1 + 1 l or 2 l one day before examination. RESULTS: There was no difference between the agents as to the quality of bowel preparation, when they were used in the same regimen. The bowel cleansing was better in both cases in the divided dose regimen (p < 0.001), and it was inversely proportional to the length of preparation (p = 0.003) and directly proportional to the length of time between the end of preparation and coloscopy (p < 0.001). PEGA was better tolerated (p < 0.028), regardless of the preparation regimen. CONCLUSION: PEG and PEGA are similarly efficient in the bowel preparation before coloscopy provided they are used in a similar regimen. The best results are reached when the preparation is divided into 2 days. PEGA is better tolerated than PEG, regardless of the used regimen. The quality of bowel cleansing is affected by the length of preparation (optimally up to 12 hours) and the time elapsed from the preparation until examination (up to 8 hours). PMID- 27250602 TI - [The role of epicardial fat and obesity parameters in the prediction of coronary heart disease]. AB - BACKGROUND: To assess the relationship of parameters of obesity in relationship to coronary angiography findings with correlation of epicardial fat (EF) thickness in uppermentioned context. METHODS: There were 80 patients examined (43 males, 37 postmenopausal females) undergoing elective coronary angiography. We examined the regular obesity parameters - BMI, waist circumference (WC), neck circumference (NC), total body fat (TBF), and visceral fat (VF) using bioimpedance. We assessed the echocardiographically measured EF thickness. We added examination of lipidogram, glycaemia, HOMA-IR (insulin resistance index) and AIP (aterogenic index of plasma). The set was divided into group with coronarographically proved stenosis or stenoses (withCS), and a group without finding of quantifiable stenosis or stenoses (withoutCS). RESULTS: The average thickness of EF in withCS group was 6.3 vs 5.6 mm in group withoutCS (p < 0.025). The differences in the thickness of EF in mentioned groups were 6.5 vs 5.2 mm in males (p < 0.025, = 20 %) and 6.1 vs 6.0 mm in females (p < 0.025, = 1.64 %). In males in withCS group, there was a dominant fat increase in epicardial region and TBF, and in females in withCS group, the fat deposits were increased in general. BMI was not a dominant parameter of adiposity in neither group (males in withCS group 31.11 vs withoutCS 30.41 kg/m(2); females in withCS group 31.40 vs withoutCS 31.20 kg/m(2)). EF was correlated the most by WC in males (r = 0.488; p < 0.005), and in females too (r = 0.564, p < 0.005). The patients in withCS group had increased HOMA-IR 4.75 vs 3.56 in withoutCS group, and AIP 0.22 vs 0.17. CONCLUSION: Thickness of EF in males and VT in females could be considered obesity parameters in assessment of pre-clinical stages of coronary atherosclerosis and prediction of risk of coronary heart disease. In adipose parameters, EF thickness was correlated the most by WC. Risk stratification of coronary artery disease is supplemented by increased HOMA-IR and AIP. PMID- 27250603 TI - [Diuretic treatment in patients with acute pulmonary edema did not produces severe hyponatremia or hypokalemia]. AB - INTRODUCTION: One of the risks of diuretic therapy for pulmonary edema is the development of hyponatremia and hypokalemia with pro-arrhythmic potential. The aim of our study was to analyze the incidence of hyponatremia and hypokalemia after the first day of treatment in a real clinical practice. METHODS: We performed a retrospective analysis of data obtained from medical records. We included all patients with pulmonary edema admitted to the coronary care unit, only patients which died within the first day of treatment were excluded. Absolute dose of administered furosemide, total fluid intake and urine output, saline and pottasium intake were analyzed. Nonparametric paired Wilcoxon test was used to compare natrium and pottasium levels changes. RESULTS: 37 patients were included into analysis. The median dose of furosemide administered during the first day of treatment was 120 mg (IQR 20-300 mg). Median diuresis was 2 400 ml (IQR 1 425-3 225 ml). The median of difference between diuresis and total fluid intake was 315 ml (IQR 538-1 380 ml). Wilcoxon test confirmed a prevailing statistically significant trend of slight rise in serum sodium within the first day of treatment (serum sodium 138.0 IQR 132.8-139.6 vs 138.1 IQR 134,0-141,7 mmol/l, p = 0.0046). The difference in serum potassium was not statistically significant (serum potassium 4.2 IQR 3.9-4.8 vs 4.2, IQR 3.8-4.8 mmol/l). CONCLUSION: Results did not confirmed the need for a substitution of sodium and potassium losses during the first day of diuretic therapy to prevent hyponatriemia and hypokalemia in patients with pulmonary edema. PMID- 27250604 TI - [Analysis of serum free light chains kappa/lambda ratio and heavy/light chain pairs of immunoglobulin to the stratification of multiple myeloma according to Mayo Stratification of Myeloma and Revised International Staging System]. AB - INTRODUCTION: Assessment of serum levels of free light chains (FLC-kappa and FLC lambda) and recently heavy/light chain pairs of immunoglobulin (HLC-kappa and HLC lambda) and their ratio (FLC-r and HLC-r) has significantly enriched traditional algorithm of multiple myeloma (MM) evaluation. The aim of the presented study was to assess the relationship of classical prognostic parameters of MM, standard FLC kappa/lambda and HLC-kappa/lambda ratio ((s)FLC-r and (s)HLC-r), modified ratio of "involved/uninvolved" FLC and HLC ((m)FLC-r and (m)HLC-r ), the difference between "involved - uninvolved" FLC and HLC (FLC-dif. and HLC-dif.) to current stratification models of MM based on the result of cytogenetic analysis. PATIENTS AND METHODS: In a group of 97 patients with MM we assessed serum levels of FLC by FreeliteTM method, and we calculated (s)FLC-r, (m)FLC-r and FLC-dif. indices by HevyliteTM method. For cytogenetic analysis we used FICTION (fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms). For MM stratification we used standard staging systems according to Durie-Salmon (D-S) and International Staging System (ISS) as well as novel stratification systems based on the results of cytogenetic analysis, ie. "Mayo Stratification of Myeloma and Risk-Adapted Therapy" (mSMART) and "Revised International Staging System" (R-ISS). RESULTS: Stratification mSMART and R-ISS has significantly different representation of "standard" or "low-risk" (71, 15.5, 11.3 a 29.9 %), "intermediate risk" (15.5, 53.6, 34 a 33 %) and "high risk" patients (13.4, 30.9, 54.7 a 37.1 %) compared to standard staging systems. mSMART stratification was compared to prognostic factors of MM (Hb, albumin, beta(2)-M, creatinine and LDH), and the only significant relationship was found in the case of beta(2)-M, R-ISS had relationship only to Hb and creatinine. In the case of D S staging we found significant relationship of stages 1-3 and substages A and B to the levels of (m)FLC-r, FLC-dif. and (m)HLC-r, ISS had moreover relationship to k HLC-dif. and MIg concentration. Analysis of mSMART stratification showed primarily significant relationship of risk categories 1-3 to (m)FLC-r and (s)HLC r indices, and R-ISS to (m)HLC-r index and MIg concentration. In both cytogenetics-based stratifications there was a lack of relationship to (s)FLC-r, FLC-dif. and HLC-dif. indices. CONCLUSION: Comparison of the results of standard staging systems according to D-S and ISS with cytogenetics based models mSMART and R-ISS showed different representation of risk groups, and significantly different relationship to classical prognostic factors together with original relationship of sMART stratification to (m)FLC-r and (s)HLC-r, and R-ISS to (m)HLC-r and MIg concentration. PMID- 27250605 TI - Prothrombin gene 20210A mutation in Slovak population. AB - INTRODUCTION: Factor V Leiden (FVL) and prothrombin G20210A mutation (PTM) are the two most common genetic polymorphisms known to predispose to a first episode of venous thromboembolism (VTE). PTM is present in 2 % Caucasian population. The main aim of this study was to identify the PTM in the patients with positive history of thrombotic events vs. control subjects. MATERIALS AND METHODS: The assessment of PTM was performed by the PCR analysis of the chromosomal DNA, which was isolated from the peripheral blood leukocytes. RESULTS: Of the 2 274 patients included, 157 (6.9 %) were carriers of the PTM. The mutation was present only in 2.6 % (n = 8) of the 303 controls. The following clinical manifestations of PTM were analysed. We observed 123 venous thrombotic events, 46 arterial thrombosis and 14 spontaneous abortions. In this article we analyse other possible risk factors for thromboembolic events in patients with carriage of PTM. CONCLUSIONS: To our knowledge, this is the largest epidemiological study of PTM in Central Europe. Employing statistical analysis, we found relatively high prevalence of the PTM in both, the patients with positive thrombosis history (6.9 %), as well as in the control group (2.6 %). The risk of thrombosis by carriage of PTM is independent of age and gender. Study has shown relatively frequent presence of double carriership of PTM and factor V Leiden mutation (FVL). PMID- 27250606 TI - [Treatment of 14 cases of Castlemans disease: the experience of one centre and an overview of literature]. AB - Castlemans disease is the term for reactive lymphocytary and plasmocytary proliferation which occurs in the unicentric (localized) form, usually without systemic symptoms, or in the generalized/multicentric form, typically with systemic symptoms (www.vzacne-diagnozy.cz). Over the past 25 years we diagnosed, treated and followed 14 histologically proven cases of Castlemans diseases. Seven patients had the localised form of the disease. In 5 of 7 cases the pathological lesion was located intrathoracically or intraabdominally and in only 2 cases it was on the surface of the body. No clinical symptoms were present in any of the patients with the unicentric form of the disease and surgical treatment led to the total removing of the disease in all of them. As opposed to that, all 7 patients with the multicentric form of Castlemans disease experienced febrile or subfebrile temperatures. Three of the 7 patients complained of severe troubling night sweats. Clinical expressions of vasculitis which was the cause of stroke, were present in 1 of 7 patients. Osteosclerotic changes on the skeleton were detected in 1 patient, who also suffered from fluid retention likely associated with this disease. Polyclonal propagation of immunoglobulins, predominantly immunoglobulin IgG type, was present in 5 of 7 patients with the multicentric form. In one case there was one complete molecule of monoclonal imunoglobuline present and in one case loose light chains kappa were increased More than 1 sampling of material for histological examination of enlarged lymph nodes were needed in 6 of 7 patients for diagnosing the multicentric form of the disease. It has turned out beneficial with respect to diagnosing the disease to carry out surgical removal and histological examination of the nodes which accumulated the most fluorodeoxyglucose within PET-CT examination. The text describes experience of the treatment. In recent years the basis for the treatment has been the monoclonal antibody antiCD20 rituximab, or thalidomide and lenalidomide, or possibly their combination. The new medicine for these patients is interleukin-6 antibody called siltuximab (Sylvant), of which we have no own experience so far. Five of our seven patients with the multicentric form received treatment, 1 patient refused treatment and in one patient the signs of the disease activity are not expressed to such extent that would require treatment. The therapy containing rituximab reached complete remission in 2 patients and the therapy containing thalidomide and lenalidomide achieved the complete remission of the disease in 3 patients. In one of the above described cases the disease did not respond to the initial treatment with rituximab and remission was reached by thalidomide and lenalidomide and in one case the disease did not respond to the initial treatment with thalidomide and complete remission was reached with rituximab. Following the treatment, no patient with the multicentric form of Castlemans disease has had a relapse until now. PMID- 27250607 TI - [Chronic kidney diseases, metformin and lactic acidosis]. AB - Chronic kidney disease and diabetes mellitus represent a worldwide public health problem. The incidence of these diseases is gradually growing into epidemic proportions. In many cases they occur simultaneously, what leads to increased morbidity and mortality among the affected patients. The majority of the patients treated for diabetes mellitus are unaware of the presence of renal insufficiency. Vascular hypertrophy and diabetic kidney disease in patients with type 2 diabetes are the most common causes of kidney failure in countries with advanced healthcare systems. Metformin is a basic drug used for the treatment of type 2 diabetes mellitus. It is excreted in an unchanged form by the kidneys. When administered to patients with renal insufficiency, sepsis, dehydration or after the parenteral administration of iodinated contrast agents, metformin can cause lactic acidosis, which is also associated with an increased mortality rate. PMID- 27250608 TI - [Beta-blockers and chronic obstructive pulmonary disease]. AB - This general article discusses the problems of beta-blockers use in patients with chronic obstructive pulmonary disease (COPD). Its aim is to refute exaggerated concerns of physicians over possible undesirable effects of beta-blockers on the patient respiratory functions and present new data on the effects of beta blockers on the extent of COPD exacerbations, bronchial reactivity and mortality of patients. PMID- 27250609 TI - [Overview of current modalities of colorectal cancer screening]. AB - There are one-step and two-steps programs for colorectal cancer screening. The aim of all screening examinations is to detect early stage of the disease in asymptomatic patient. The aim of this article is actual review of current screening modalities such as fecal occult blood test, flexible sigmoideoscopy, colonoscopy, CT colonography, capsule endoscopy, blood-based tests and stool DNA tests. Colonoscopy still remains the gold standard for detection of colorectal neoplasias. In majority of countries worldwide programs for colorectal cancer screening are based on immunochemical fecal occult blood test followed by colonoscopy when positive. PMID- 27250610 TI - [The effect of antihypertensive treatment on patients with diabetes depends on the values of blood pressure: a systematic survey and meta-analyses]. AB - What was already known about these problems before the publication of the Northern Swedish study? Hypertension is the most important risk factor for mortality and cardiovascular disease on a global scale. Patients with diabetes mellitus demonstrate an increased risk for cardiovascular disease and they often also have hypertension at the same time. Antihypertensive treatment reduces the risk of cardiovascular diseases in patients with diabetes, however an optimum value of blood pressure is a matter of debate. What is the special contribution of the Swedish study? Antihypertensive treatment in patients with diabetes and a systolic pressure higher than 140 mm Hg brings with it a decreased risk of mortality and cardiovascular disease. Antihypertensive treatment in patients with dia-betes and a systolic lower than 140 mm Hg, however, brings with it an increased risk of mortality and cardiovascular disease. The interaction between systolic pressure values before the treatment and during it is significant. PMID- 27250611 TI - [What are the effects of fixed-dose combination of candesartan and amlodipine]. AB - We are presenting a current view on a fixed-dose combination of amlodipine and candesartan in the treatment of hypertension. Major studies on the individual preparations as well as studies examining their combination are included. This fixed-dose combination expands our possibilities with regard to attaining the blood pressure target values, in particular in patients with risk factors or patients with comorbidities. Finally, the benefit mainly consists in the greater compliance of the patient with a minimum adverse effects. PMID- 27250612 TI - [Are some antidiabetic drugs also drugs useful for heart failure treatment?]. AB - The prevalence of diabetes mellitus type 2 is rapidly growing. It is the cardiovascular mortality and morbidity why these patients suffer. Also heart failure becomes very frequent in diabetics, as it is a strong risk factor for development of heart failure and for its progression. Recently published data of EMPA-REG OUTCOME trial with empagliflozin hint to the possibility of heart failure treatment with this drug. The author presents data about the influence of antidiabetic drugs on cardiovascular risk factors, specifically on heart failure. This can be a way how to prevent heart failure in diabetic patients. Later he presents data about the influence of antidiabetics on symptoms and signs of heart failure. Some of these drugs are neutral, some are risky for patients and in the case of empagliflozin there is a beneficial influence. As heart failure is a great problem of clinical practice and diabetes is a strong risk factor of heart failure, we are looking also for prevention of heart failure and for its treatment also by using antidiabetic drug. PMID- 27250613 TI - [PCSK9 inhibitors - new possibilities in the treatment of hypercholesterolemia: For which patients will be indicated?Czech atherosclerosis society statement]. AB - First line drug for the treatment of hypercholesterolemia are statins, which reduce LDL-cholesterol up to 50 %; such reduction is sufficient for most patients to achieve the target values. The exceptions are patients with familial hypercholesterolemia and patients with statin intolerance. To achieve target LDL cholesterol in these two groups of patients will be possible with new drugs - PCSK9 inhibitors, which decrease LDL-cholesterol by an additional 50-60 %. The first two PCSK9 inhibitors (alirocumab and evolocumab) already had been approved for clinical use by European regulatory authorities. The primary indication for combination statin with PCSK9 inhibitor should be undoubtedly patients with a confirmed diagnosis of familial hypercholesterolemia, who are treated in the Czech Republic primarily in specialized centers of MedPed project. Furthermore, this treatment should be available for other patients at very high risk of cardiovascular diseases, who cannot achieve target LDL-cholesterol (eg. for statins intolerance). PMID- 27250614 TI - [DRESS syndrome]. AB - DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is severe drug induced allergic-type reaction which occurs few days to weeks after taking a drug in a predisposed patient. Organ damage, eosinophilia and skin rash are typical at presentation. Corticotherapy is often necessary in severe cases. In this report we describe a case of 56-year old female with fever, elevated liver tests and skin rash. DRESS syndrome was diagnosed and allopurinol was indentified as a causative drug. Due to possible fatal outcome, DRESS syndrome should be considered in a differential diagnosis of all patients presenting with similar signs and symptoms. PMID- 27250615 TI - Practice comparisons between accelerated resolution therapy, eye movement desensitization and reprocessing and cognitive processing therapy with case examples. AB - Recent outcomes for Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) therapy indicate that as many as 60-72% of patients retain their PTSD diagnosis after treatment with CPT or PE. One emerging therapy with the potential to augment existing trauma focused therapies is Accelerated Resolution Therapy (ART). ART is currently being used along with evidence based approaches at Fort Belvoir Community Hospital and by report has been both positive for clients as well as less taxing on professionals trained in ART. The following is an in practice theoretical comparison of CPT, EMDR and ART with case examples from Fort Belvoir Community Hospital. While all three approaches share common elements and interventions, ART distinguishes itself through emphasis on the rescripting of traumatic events and the brevity of the intervention. While these case reports are not part of a formal study, they suggest that ART has the potential to augment and enhance the current delivery methods of mental health care in military environments. PMID- 27250616 TI - How personal standards perfectionism and evaluative concerns perfectionism affect the error positivity and post-error behavior with varying stimulus visibility. AB - Error detection is required in order to correct or avoid imperfect behavior. Although error detection is beneficial for some people, for others it might be disturbing. We investigated Gaudreau and Thompson's (Personality and Individual Differences, 48, 532-537, 2010) model, which combines personal standards perfectionism (PSP) and evaluative concerns perfectionism (ECP). In our electrophysiological study, 43 participants performed a combination of a modified Simon task, an error awareness paradigm, and a masking task with a variation of stimulus onset asynchrony (SOA; 33, 67, and 100 ms). Interestingly, relative to low-ECP participants, high-ECP participants showed a better post-error accuracy (despite a worse classification accuracy) in the high-visibility SOA 100 condition than in the two low-visibility conditions (SOA 33 and SOA 67). Regarding the electrophysiological results, first, we found a positive correlation between ECP and the amplitude of the error positivity (Pe) under conditions of low stimulus visibility. Second, under the condition of high stimulus visibility, we observed a higher Pe amplitude for high-ECP-low-PSP participants than for high-ECP-high-PSP participants. These findings are discussed within the framework of the error-processing avoidance hypothesis of perfectionism (Stahl, Acharki, Kresimon, Voller, & Gibbons, International Journal of Psychophysiology, 97, 153-162, 2015). PMID- 27250617 TI - The osteoblast as an inflammatory cell: production of cytokines in response to bacteria and components of bacterial biofilms. AB - BACKGROUND: Implant infections are a major complication in the field of orthopaedics. Bacteria attach to the implant-surface and form biofilm-colonies which makes them difficult to treat. Not only immune cells exclusively respond to bacterial challenges, but also local tissue cells are capable of participating in defense mechanisms. The aim of this study was to evaluate the role of osteoblasts in the context of implant infections. METHODS: Primary osteoblasts were cultivated and stimulated with free-swimming bacteria at 4 degrees C and 37 degrees C. Supernatants were harvested for ELISA and expression of pro inflammatory cytokines evaluated by RT-PCR. Bacterial binding to osteoblasts was evaluated using cytofluorometry and uptake was investigated by (3)H thymidine labelling of bacteria. Osteoblasts were additionally stimulated with the extracellular polymeric substance (EPS) of Staphylococcus epidermidis biofilms, as well as components of the EPS; the bacterial heat shock protein GroEL in particular. RESULTS: We demonstrated that binding of bacteria to the osteoblast cell surface leads to an increased production of pro-inflammatory cytokines. Bacteria are capable of surviving intracellular. Furthermore, osteoblasts do not only respond to free-swimming, planktonic bacteria, but also to components of the EPS, including lipoteichoic acid and the heat shock protein GroEL. CONCLUSION: In conclusion, local tissue cells, specifically osteoblasts, might contribute to the persistence of the inflammatory response associated with implant-infections. PMID- 27250619 TI - Osteochondritis dissecans of the medial femoral condyle : New cell-free scaffold as a treatment option. AB - There is no gold standard in treating osteochondral lesions, which is why the treatment remains very challenging. Osteochondral defects can occur in any joint, but the most common locations are the knee and the ankle. Trauma, repeated microtrauma, avascular necrosis and osteochondritis dissecans (a special type of avascular necrosis) are blamed for the cartilage damage and the damage of adjacent subchondral bone. The self-healing ability of the cartilage is unfortunately very poor; thus, it is necessary to develop new methods of cartilage repair. Unfortunately, few data and long-term survival rates for these new scaffolds are available. We report a case of osteochondritis dissecans treated with a new cell-free scaffold MaioRegen(r) (Fin-Ceramica Faenza Spa, Faenza, Italy). PMID- 27250618 TI - [Bernese periacetabular osteotomy. : Indications, technique and results 30 years after the first description]. AB - The Bernese periacetabular osteotomy (PAO) is a surgical technique for the treatment of (1) hip dysplasia and (2) femoroacetabular impingement due to acetabular retroversion. The aim of the surgery is to prevent secondary osteoarthritis by improvement of the hip biomechanics. In contrast to other pelvic osteotomies, the posterior column remains intact with this technique. This improves the inherent stability of the acetabular fragment and thereby facilitates postoperative rehabilitation. The birth canal remains unchanged. Through a shortened ilioinguinal incision, four osteotomies and one controlled fracture around the acetabulum are performed. The direction of acetabular reorientation differs for both indications while the sequence of the osteotomies remains the same. This surgical approach allows for a concomitant osteochondroplasty in the case of an aspherical femoral head-neck junction. The complication rate is relatively low despite the complexity of the procedure. The key point for a successful long term outcome is an optimal reorientation of the acetabulum for both indications. With an optimal reorientation and a spherical femoral head, the cumulative survivorship of the hip after 10 years is 80-90 %. For the very first 75 patients, the cumulative 20-year survivorship was 60 %. The preliminary evaluation of the same series at a 30-year follow-up still showed a survivorship of approximately 30 %. The PAO has become the standard procedure for the surgical therapy of hip dysplasia in adolescents and adults. PMID- 27250620 TI - [The growing spine : Normal and abnormal development]. AB - Growth of the pediatric spine occurs in phases. The first 5 years of life are characterized by rapid growth. The lower extremities and trunk contribute equally to the entire growth by 50 % each. In the following years, until the onset of puberty, a steady but reduced rate of growth is observed. During these years a T1 S1 growth of only 1 cm per year can be detected and the spine contributes only one third to the entire growth. Puberty consists of an acceleration phase lasting 2 years. In the first year of this phase the growth peak of the extremities and in the following year the growth peak of the spine can be noticed. The ensuing deceleration phase of puberty lasts for 3 years. During that period the development of the Risser sign, menarche, and fusion of the trochanter epiphysis are taking place. Clinical parameters such as sitting height, standing height, and arm span may be used to evaluate growth. Important radiological parameters include the Risser sign, the determination of skeletal age according to Greulich and Pyle, and the T1-T12 height. The use of the olecranon method during the ascending phase of puberty can be recommended. Problems of the developing spine may include malformations, developmental disruptions or deformations. According to their manifestations they have a different prognosis, which can be estimated by knowledge of residual growth and the typical course of spinal growth in childhood. PMID- 27250621 TI - [Uncertainties and challenges when facing new and emerging occupational risks]. PMID- 27250622 TI - [Archivos 2015: an Open Access journal]. PMID- 27250623 TI - [Descriptive Study of sickness absence in the health care sector of Catalonia (2009-2012)]. AB - OBJECTIVE: To describe the incidence and evolution of sickness absence (SA) for non-occupational and occupational illness/injury in the population of workers in Catalonian Health Centers based on the definition of a set of common indicators. METHODS: The study population consisted of 25,964 workers from 30 health centers in Catalonia, during 2009-2012. Information on SA episodes was obtained from records of the Directorate of Human Resources. SA indicators were defined, and SA incidence rates and temporal evolution were calculated, depending on the length and type of episode, and the size and activity of health centers. RESULTS: SA incidence rates for non-occupational illness and injury showed a decreasing trend during 2009-2012. Smaller centers had lower SA rates for non-occupational conditions than larger centers (p<0.001). Social health centers had higher SA rates of non-occupational illness and injury, especially those with a very short duration (p<0.001). Primary care centers had the lowest SA occupational illness and injury rates, with the highest rates occurring in the social health centers, especially long-term centers (p<0.001). CONCLUSIONS: The differences in incidence rates of SA detected by type of activity of the health centers could be due to differences in working conditions. PMID- 27250624 TI - [Update the wood dust exposure values included in the job-exposure matrix MatEmESp by making use of the WOODEX database]. AB - OBJECTIVE: To revise and complete information on prevalence and intensity of wood dust exposure among Spanish workers in the MatEmESp job-exposure matrix, based on data from the WOODEX database. METHODS: Exposure groups by economic activity in WOODEX were linked to the occupations in MatEmESp. The WOODEX data were then used to calculate new values of exposure prevalence and intensity for the occupations included in MatEmESp. RESULTS: A total of 18 occupations in MatEmESp were linked to exposure groups in the WOODEX database. This allowed estimation of new exposure intensity values for these 18 occupations and calculation of new exposure prevalence values for 16 of them. In addition, a new at-risk occupation, previously not in MatEmESp, was identified. The occupations with the highest prevalence values are sawmill operators (CNO-94 code 8141) and operators of machinery for making wood products (CNO-94 code 8340). The new calculations indicate that 10.5% of at-risk workers in MatEmESp are exposed to concentrations above 5 mg/m3. CONCLUSIONS: The WOODEX data provided more detailed information about exposure profiles to wood dust and are mainly based on Spanish data. In contrast, 95% of the data on wood dust exposure inMatEmESp is based on extrapolations from other countries or on expert considerations. PMID- 27250625 TI - [Should psychosocial risk factors associated with working conditions be evaluated?]. PMID- 27250626 TI - [Should psychosocial risk factors associated with working conditions be evaluated?]. PMID- 27250627 TI - Anti-dsDNA antibodies bind to TLR4 and activate NLRP3 inflammasome in lupus monocytes/macrophages. AB - BACKGROUND: NLRP3 inflammasome has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The activation of NLRP3 inflammasome results in the production of IL-1beta and the subsequent inflammation. Anti-dsDNA antibodies (anti-dsDNA Abs) play critical roles in the development and progression of SLE. However, the mechanism of NLRP3 inflammasome activation in SLE is still not known. This study investigated the activation of NLRP3 inflammasome stimulated by anti-dsDNA Abs in monocytes/macrophages from SLE patients. METHODS: Monocytes/macrophages from SLE patients or healthy controls were stimulated with anti-dsDNA Ab-positive serum or purified anti-dsDNA Abs. Activation of inflammasome was measured by flow cytometry or Western blot. Anti dsDNA Abs isolated from active SLE patients were injected into female (NZB * NZW) F1 mice and the activation of NLRP3 inflammasome and the frequencies of Th17 and Treg were examined. RESULTS: The activity of caspase-1 was significantly increased in active SLE patients and was correlated with serum levels of anti dsDNA Abs and disease activities. The concentrations of IL-1beta and IL-17A were also significantly higher in SLE patients compared to healthy controls. Anti dsDNA Ab-positive serum rather than healthy serum or RF (rheumatoid factor) positive serum stimulated the activation of caspase-1 in monocytes. Anti-dsDNA Abs bound to TLR4 on macrophages and induced the production of ROS. Mitochondria targeting antioxidant Mito-TEMPO, IkappaB kinase inhibitor peptide or TLR4 siRNA inhibited the activation of NLRP3 inflammasome and the secretion of IL-1beta induced by anti-dsDNA Abs. Injection of anti-dsDNA Abs into (NZB * NZW) F1 mice resulted in increased caspase-1 activation and production of IL-1beta and IL-17A. The Th17/Treg cell ratio also significantly increased following anti-dsDNA Ab injection. CONCLUSIONS: Anti-dsDNA Abs activated NLRP3 inflammasome in monocytes/macrophages from SLE patients by binding to TLR4 and inducing the production of mitochondrial ROS. PMID- 27250628 TI - Blood Biomarkers in Minor Stroke and Transient Ischemic Attack. AB - Minor stroke and transient ischemic attack (TIA) are common disorders with a high rate of subsequent disabling stroke, so the early recognition and management of minor stroke and TIA is of great importance. At the moment, the diagnosis of these disorders is based on neurologic deficits in a stroke-clinician's examination of the patient, supplemented by the results of acute brain imaging. However, high variability in TIA diagnosis has been reported between physicians, even trained vascular neurologists, and image-based diagnostic confirmation is not always readily available. Some patients still have ischemic events despite sustained standard secondary preventive therapy. Blood biomarkers are promising to aid in the diagnosis, risk stratification, and individual treatment of minor stroke and TIA. Some studies are being conducted in this field. This mini-review aims to highlight potential biomarkers for diagnosis and those helpful in predicting the risk of future stroke and the selection of treatment. PMID- 27250630 TI - Robust Statistical Detection of Power-Law Cross-Correlation. AB - We show that widely used approaches in statistical physics incorrectly indicate the existence of power-law cross-correlations between financial stock market fluctuations measured over several years and the neuronal activity of the human brain lasting for only a few minutes. While such cross-correlations are nonsensical, no current methodology allows them to be reliably discarded, leaving researchers at greater risk when the spurious nature of cross-correlations is not clear from the unrelated origin of the time series and rather requires careful statistical estimation. Here we propose a theory and method (PLCC-test) which allows us to rigorously and robustly test for power-law cross-correlations, correctly detecting genuine and discarding spurious cross-correlations, thus establishing meaningful relationships between processes in complex physical systems. Our method reveals for the first time the presence of power-law cross correlations between amplitudes of the alpha and beta frequency ranges of the human electroencephalogram. PMID- 27250629 TI - Epigenetic and SP1-mediated regulation is involved in the repression of galactokinase 1 gene in the liver of neonatal piglets born to betaine supplemented sows. AB - PURPOSE: In this study, we sought to investigate the effects of maternal betaine supplementation on the expression and regulation of GALK1 gene in the liver of neonatal piglets. METHODS: Sixteen sows of two groups were fed control or betaine supplemented diets (3 g/kg), respectively, throughout the pregnancy. Newborn piglets were individually weighed immediately after birth, and one male piglet close to mean body weight from the same litter was selected and killed before suckling. Serum samples of newborn piglets were analyzed for biochemical indexes, hormone and amino acid levels. Liver samples were analyzed for GALK1 expression by real-time PCR and western blotting, while GALK1 regulational mechanism was analyzed by methylated DNA immunoprecipitation, chromatin immunoprecipitation and microRNAs expression. RESULTS: Betaine-exposed neonatal piglets had lower serum concentration of galactose, which was associated with significantly down regulated hepatic GALK1 expression. The repression of GALK1 mRNA expression was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter. Binding sites of SP1, GR and STAT3 were predicted on GALK1 promoter, and decreased SP1 protein content and lower SP1 binding to GALK1 promoter were detected in the liver of betaine-exposed piglets. Furthermore, the expression of miRNA-149 targeting GALK1 was up-regulated in the liver of betaine exposed piglets, along with elevated miRNAs-processing enzymes Dicer and Ago2. CONCLUSIONS: Our results suggest that maternal dietary betaine supplementation during gestation suppresses GALK1 expression in the liver of neonatal piglets, which involves complex gene regulation mechanisms including DNA methylation, histone modification, miRNAs expression and SP1-mediated transcriptional modulation. PMID- 27250631 TI - Are atypical lymphocytes present with viral influenza-like illnesses (ILIs) in hospitalized adults? AB - The purpose of this investigation was to determine if atypical lymphocytes were of diagnostic value in viral influenza-like illnesses (ILIs) in hospitalized adults during the influenza season. Are atypical lymphocytes present with viral ILIs in hospitalized adults? During the influenza season, hospitals are inundated with influenza and viral ILIs, e.g., human parainfluenza virus-3 (HPIV-3). Without specific testing, clinically, it is difficult to differentiate influenza from ILIs, and surrogate influenza markers have been used for this purpose, e.g., relative lymphopenia. The diagnostic significance of atypical lymphocytes with ILIs is not known. We retrospectively reviewed the charts of 35 adults admitted with pneumonia due to viral ILI. The diagnosis of 14 patients was by respiratory virus polymerase chain reaction (PCR). During the 2015 influenza A season with ILIs, atypical lymphocytes were not present in influenza A (H3N2) patients but atypical lymphocytes were present in some ILIs, particularly HPIV-3. With viral ILIs, atypical lymphocytes should suggest a non-influenza viral diagnosis. PMID- 27250632 TI - Tongue coating frequency and its colonization by yeasts in chronic kidney disease patients. AB - The objective of this study was to investigate tongue coating (TC) frequency and its colonization by yeasts in a group of chronic kidney disease (CKD) patients. Clinical examination of the oral mucosa of 33 CKD patients was performed to investigate oral and tongue lesions. TC was diagnosed according to its clinical characteristics. Stimulated saliva and TC samples were collected to verify the salivary flow, and determine yeast frequency, species and counts. TC was found in 18/33 of the patients (54.55 %) and was the most frequent oral lesion found. Of 18 patients with TC, 13 (72.22 %) presented positive cultures for yeasts on the tongue dorsum, and one (5.55 %) in the saliva only. Yeasts were significantly more frequent in the tongue dorsum when compared to the saliva (p = 0.0106). The most frequent yeast species found was C. albicans (55.55 %), while C. parapsilosis comprised 50 % of non-albicans Candida species. This study demonstrated high amounts of yeasts on the cultures from TC samples of CKD patients, strongly suggesting that TC is a clinical representation of a polymicrobial biofilm, which could serve as a gateway for disseminated infection in immunosuppressed patients undergoing frequent hospitalization. PMID- 27250633 TI - Emergence of co-production of plasmid-mediated AmpC beta-lactamase and ESBL in cefoxitin-resistant uropathogenic Escherichia coli. AB - Plasmid-mediated AmpC (pAmpC) and ESBL co-production was detected in Escherichia coli a major etiologic agent of urinary tract infection. Isolates resistant to cefoxitin by CLSI methodology were tested for pAmpC beta-lactamase using phenylboronic acid and ESBLs by combined disk diffusion method. pAmpC/ESBL genes were characterized by PCR and sequencing. Transconjugation experiments were done to study the transfer of pAmpC and ESBL production from clinical isolates as donor to E. coli J53 AziR as recipient. Incompatibility groups of transmissible plasmids were classified by PCR-based replicon typing (PBRT). Among 148 urine culture positive isolates, E. coli was reported in 39.86 % (59/148), with 93.22 % (55/59) of cefoxitin resistance. pAmpC production was detected in 25, with varied distribution of blaCMY-2 and blaDHA-1type genes alone (n = 13 and 7 respectively) or in combination (n = 5). ESBL co-production was observed in 88 % (22/25) of pAmpC producing isolates with predominance of blaTEM (n = 20). Twenty-three transconjugants showed transmission of pAmpC-and ESBL-resistant genes with co carriage of blaCMY-2 and blaTEM (n = 15) in plasmids of IncF type (n = 9) being predominant, followed by IncI1 (n = 4) and IncH1 (n = 2) in combination. All clinical isolates were clonally diverse. Resistance against different beta lactams in uropathogenic E. coli has been an emerging concern in resource- poor countries such as India. Knowledge on the occurrence of AmpC beta-lactamases and ESBL amongst this pathogen and its transmission dynamics may aid in hospital infection control. PMID- 27250635 TI - Stem Cells in Bone Regeneration. AB - Bone has the capacity to regenerate and repair itself. However, this capacity may be impaired or lost depending on the size of the defect or the presence of certain disease states. In this review, we discuss the key principles underlying bone healing, efforts to characterize bone stem and progenitor cell populations, and the current status of translational and clinical studies in cell-based bone tissue engineering. Though barriers to clinical implementation still exist, the application of stem and progenitor cell populations to bone engineering strategies has the potential to profoundly impact regenerative medicine. PMID- 27250634 TI - Beyond Return to Work: The Effect of Multimorbidity on Work Functioning Trajectories After Sick Leave due to Common Mental Disorders. AB - Objectives Patients with common mental disorders (CMDs) often suffer from comorbidities, which may limit their functioning at work. We assessed the longitudinal impact of multimorbidity, defined as two or more co-occurring chronic health conditions, on work functioning over time among workers who had returned to work after sick leave due to CMDs. Methods Prospective cohort study of 156 workers followed for 1 year after return to work from sick leave due to CMDs. A multimorbidity score was computed by counting severity-weighted chronic health conditions measured at baseline. Work functioning was measured at baseline and at 3, 6 and 12 months follow-up with the Work Role Functioning Questionnaire. Work functioning trajectories, i.e. the course of work functioning after return to work over time, were identified through latent class growth analysis. Results A total of 44 % of workers had multimorbidity. Four work functioning trajectories were identified: one (12 % of the workers) showed increasing work functioning scores during follow-up, whereas the other trajectories showed low, medium and high scores (23, 41 and 25 %, respectively) that remained stable across time points. Although multimorbidity did not predict membership in any trajectory, within the increasing score trajectory levels of work functioning were lower among those with high baseline multimorbidity score (p < 0.001). Conclusions Over time, multimorbidity negatively impacts work functioning after return to work from sick leave due to CMDs. PMID- 27250637 TI - Bariatric surgery for obese adolescents to prevent type 2 diabetes. PMID- 27250636 TI - Identification of a novel PPARbeta/delta/miR-21-3p axis in UV-induced skin inflammation. AB - Although excessive exposure to UV is widely recognized as a major factor leading to skin perturbations and cancer, the complex mechanisms underlying inflammatory skin disorders resulting from UV exposure remain incompletely characterized. The nuclear hormone receptor PPARbeta/delta is known to control mouse cutaneous repair and UV-induced skin cancer development. Here, we describe a novel PPARbeta/delta-dependent molecular cascade involving TGFbeta1 and miR-21-3p, which is activated in the epidermis in response to UV exposure. We establish that the passenger miRNA miR-21-3p, that we identify as a novel UV-induced miRNA in the epidermis, plays a pro-inflammatory function in keratinocytes and that its high level of expression in human skin is associated with psoriasis and squamous cell carcinomas. Finally, we provide evidence that inhibition of miR-21-3p reduces UV-induced cutaneous inflammation in ex vivo human skin biopsies, thereby underlining the clinical relevance of miRNA-based topical therapies for cutaneous disorders. PMID- 27250638 TI - Personal utility is inherent to direct-to-consumer genomic testing. AB - People for and against direct-to-consumer (DTC) genomic tests are arguing around two issues: first, on whether an autonomy-based account can justify the tests; second, on whether the tests bring any personal utility. Bunnik et al, in an article published in this journal, were doubtful on the latter, especially in clinically irrelevant and uninterpretable sequences, and how far this claim could go in the justification. Here we argue that personal utility is inherent to DTC genomic tests and their results. We discuss Bunnik et al's account of personal utility and identify problems in its motivation and application. We then explore concepts like utility and entertainment which suggest that DTC genomic tests bring personal utility to their consumers, both in the motivation and the content of the tests. This points to an alternative account of personal utility which entails that entertainment value alone is adequate to justify DTC genomic tests, given appropriate strategies to communicate tests results with the consumers. It supports the autonomy-based justification of the test by showing that DTC genomic test itself stands as a valuable option and facilitates meaningful choice of the people. PMID- 27250639 TI - Formulation and characterization of Turkish oregano microcapsules prepared by spray-drying technology. AB - The aim of this study was optimization of spray-drying process conditions for microencapsulation of Turkish oregano extract. Different concentrations of maltodextrin and gum arabic as encapsulating agents (wall material) as well as influence of selected processing variables were evaluated. The optimal conditions were maintained on the basis of the load of main bioactive compounds - ursolic, rosmarinic acids and carvacrol - in prepared microparticles after comparison of all significant response variables using desirability function. Physicomechanical properties of powders such as flowability, wettability, solubility, moisture content as well as product yield, encapsulation efficiency (EE), density, morphology and size distribution of prepared microparticles have been determined. The results demonstrated that the optimal conditions for spray-drying mixture consisted of two parts of wall material solution and one part of ethanolic oregano extract when the feed flow rate was 40 mL/min and air inlet temperature 170 degrees C. Optimal concentration of wall materials in solution was 20% while the ratio of maltodextrin and gum arabic was 8.74:1.26. PMID- 27250640 TI - Enantiomeric two-armed lanthanide-binding tags for complementary effects in paramagnetic NMR spectroscopy. AB - Two-armed lanthanide-binding tags induce significant, long-range paramagnetic effects in the NMR spectra of attached proteins. An enantiomeric pair of rigid, two-armed, cyclen-based tags are reported that produce markedly different effects from the same tagging site, allowing for the measurement of complementary paramagnetic restraints for structural studies. PMID- 27250641 TI - EphrinB2 regulates the emergence of a hemogenic endothelium from the aorta. AB - Adult-type intraembryonic hematopoiesis arises from specialized endothelial cells of the dorsal aorta (DA). Despite the critical importance of this specialized endothelium for establishment of hematopoietic stem cells and adult hematopoietic lineages, the mechanisms regulating its emergence are incompletely understood. We show that EphrinB2, a principal regulator of endothelial cell function, controls the development of endothelium producing adult-type hematopoiesis. The absence of EphrinB2 impairs DA-derived hematopoiesis. Transmembrane EphrinB2 and its EphB4 receptor interact in the emerging DA, which transiently harbors EphrinB2(+) and EphB4(+) endothelial cells, thereby providing an opportunity for bi-directional cell-to-cell signaling to control the emergence of the hemogenic endothelium. Embryonic Stem (ES) cell-derived EphrinB2(+) cells are enriched with hemogenic endothelial precursors. EphrinB2 silencing impairs ES generation of hematopoietic cells but not generation of endothelial cells. The identification of EphrinB2 as an essential regulator of adult hematopoiesis provides important insight in the regulation of early hematopoietic commitment. PMID- 27250642 TI - Localized Morphea Developing in a Scar After Breast Carcinoma Surgery in the Absence of Radiotherapy. PMID- 27250644 TI - Identification of novel selective MMP-9 inhibitors as potential anti-metastatic lead using structure-based hierarchical virtual screening and molecular dynamics simulation. AB - MMP-9 is an attractive target for the development of new anticancer drugs. In the current study, pharmacophore modeling was employed using two highly active and selective gelatinase inhibitors obtained from two X-ray crystal structures (PDB IDs: and ) to identify novel selective MMP-9 inhibitors. The derived model was refined manually and also validated by the GH scoring method. The refined pharmacophore model, ADRR, was able to retrieve 86% of actives with a GH score of 0.774, indicating that the model was capable of retrieving the active MMP-9 inhibitors. ADRR was used to screen 2 838 166 unique structures. Hit filtration was carried out using a fitness score >1.5 and drug-likeness properties. Hierarchical clustering generates 33 clusters based on diversity. A total of 33 molecules were obtained and these molecules were taken for cross-docking studies with 5 subtype MMPs. Among 33 tested, 2 molecules, P10A-0000088030 (Lig-1) and P10A-0001383812 (Lig-2), were found to have the highest docking scores (-8.59 kcal mol(-1) and -8.27 kcal mol(-1)) towards MMP-9 compared with the other MMPs. Further MM-GBSA analysis was performed for two hits with 5 subtype MMPs to reveal the essential features that contribute to selectivity. The results showed that van der Waals contributions play a central role in determining the selectivity of MMP-9 inhibitors. Molecular dynamics studies were carried out for total time of 330 ns to assess the stability of ligands at the active site. MD analysis showed that binding of Lig-1 with MMP-9 is stable compared to that with Lig-2. Hence, we suggest the Lig-1 compound as a good lead in designing novel potent inhibitors of MMP-9. PMID- 27250645 TI - Structural and chemical analysis of gadolinium halides encapsulated within WS2 nanotubes. AB - The hollow cavities of nanotubes serve as templates for the growth of size- and shape-confined functional nanostructures, giving rise to novel materials and properties. In this work, considering their potential application as MRI contrast agents, gadolinium halides are encapsulated within the hollow cavities of WS2 nanotubes by capillary filling to obtain GdX3@WS2 nanotubes (where X = Cl, Br or I and @ means encapsulated in). Aberration corrected scanning/transmission electron microscopy (S/TEM) and spectroscopy is employed to understand the morphology and composition of the GdI3@WS2 nanotubes. The three dimensional morphology is studied with STEM tomography but understanding the compositional information is non-trivial due to the presence of multiple high atomic number elements. Therefore, energy dispersive X-ray spectroscopy (EDS) tomography was employed revealing the three dimensional chemical composition. Molecular dynamics simulations of the filling procedure shed light into the mechanics behind the formation of the confined gadolinium halide crystals. The quasi-1D system employed here serves as an example of a TEM-based chemical nanotomography method that could be extended to other materials, including beam-sensitive soft materials. PMID- 27250643 TI - Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody. AB - Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia and inflammatory diseases. Because anti-HTLV-1 immune responses are critical for suppressing infected cells, enhancing cellular immunity is beneficial for the treatment of HTLV-1-associated diseases. Using simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaques, we analyzed the immune responses to viral antigens and the dynamics of virus-infected cells. The chemokine receptor CCR4 is expressed on STLV-1 infected cells, and administration of humanized monoclonal antibody to CCR4, mogamulizumab, dramatically decreased the number of STLV-1 infected cells in vivo. Concurrently, mogamulizumab treatment enhanced STLV-1 specific CD4(+) and CD8(+) T cell responses by simultaneously targeting CCR4(+) effector regulatory T (Treg) cells and infected cells. Mogamulizumab promoted the phagocytosis of CCR4(+) infected cells by macrophages, which likely enhanced antigen presentation. Vaccination with recombinant vaccinia virus (rVV) expressing viral antigens suppressed the proviral load and the number of Tax expressing cells. Enhanced T-cell responses were also observed in some ATL patients who were treated with mogamulizumab. This study shows that mogamulizumab works not only by killing CCR4(+) infected cells directly, but also by enhancing T cell responses by increasing the phagocytosis of infected cells by antigen presenting cells and suppressing CCR4(+) effector Treg cells. PMID- 27250647 TI - Tunable ultraviolet and blue light generation from Nd:YAB random laser bolstered by second-order nonlinear processes. AB - Ultraviolet and blue light were obtained by nonlinear frequency conversion in a random laser (RL) based on Nd0.10Y0.90Al3(BO3)4 nanocrystalline powder. RL operation at 1062 nm, due to the (4)F3/2 -> (4)I11/2 transition of neodymium ions (Nd(3+)), was achieved by exciting the Nd(3+) with a tunable beam from 680 to 920 nm covering the ground state absorption transitions to the (4)F9/2, ((4)F7/2,(4)S3/2), ((4)F5/2,(2)H9/2), and (4)F3/2 states. Light from 340 to 460 nm was obtained via the second-harmonic generation of the excitation beam while tunable blue light, from 417 to 486 nm, was generated by self-sum-frequency mixing between the excitation beam and the RL emission. PMID- 27250648 TI - Interface induce growth of intermediate layer for bandgap engineering insights into photoelectrochemical water splitting. AB - A model of interface induction for interlayer growing is proposed for bandgap engineering insights into photocatalysis. In the interface of CdS/ZnS core/shell nanorods, a lamellar solid solution intermediate with uniform thickness and high crystallinity was formed under interface induction process. Merged the novel charge carrier transfer layer, the photocurrent of the core/shell/shell nanorod (css-NR) array was significantly improved to 14.0 mA cm(-2) at 0.0 V vs. SCE, nearly 8 times higher than that of the perfect CdS counterpart and incident photon to electron conversion efficiency (IPCE) values above 50% under AM 1.5G irradiation. In addition, this array photoelectrode showed excellent photocatalytic stability over 6000 s. These results suggest that the CdS/Zn1 xCdxS/ZnS css-NR array photoelectrode provides a scalable charge carrier transfer channel, as well as durability, and therefore is promising to be a large-area nanostructured CdS-based photoanodes in photoelectrochemical (PEC) water splitting system. PMID- 27250649 TI - Operator eye doses during computed tomography fluoroscopic lung biopsy. AB - The aim of this work was to examine the peak entrance surface air kerma (peak ESAK) to the eyes during CT fluoroscopy lung biopsy, and the impact of lead glasses, exposure parameters, head rotation, and height on peak ESAK to the eyes. Two phantoms simulating the patient and radiologist were used, and 108 exposures were made using a 16-slice Toshiba Alexion CT scanner (Toshiba Medical Systems, Nasu, Japan). ESAK to the phantom radiologist's right eye was measured using an Unfors Xi dosimeter (RaySafe, Billdal, Sweden) with and without lead glasses at two kilovoltages (120 kVp and 135 kVp) and three milliampere settings (10 mA, 20 mA, and 30 mA. A paired t test was used to compare peak ESAK to the eye at different angles, heights, and kVp and mA with and without lead glasses. Peak ESAK was higher without compared to with lead glasses (p ? 0.001). The peak ESAK to the eyes increased as the phantom radiologist rotated toward the gantry without lead glasses, from 2.42 MUGy at 120 degrees to 10.54 MUGy at 30 degrees (p = 0.001). No significant difference was noted in peak ESAK with change in phantom radiologist height (p > 0.05). An increase from 120 kVp to 135 kVp resulted in 23% and 26% increases in peak ESAK with and without lead glasses respectively (p = 0.001). An increase of tube current from 10 mA to 20 mA almost doubled peak ESAK (p = 0.005). Findings demonstrate that lead glasses reduce ESAK to the eyes, and that increased kVp, mA, and eye rotation to the gantry increase ESAK to the eyes. PMID- 27250650 TI - The clinical frailty scale predicts functional decline and mortality when used by junior medical staff: a prospective cohort study. AB - BACKGROUND: Increasing frailty is associated with risk of mortality and functional decline in hospitalized older adults, but there is no consensus on the best screening method for use by non-geriatricians. The objective of this study is to determine whether the clinical frailty scale (CFS) can be used to identify patient baseline frailty status in the acute general medical setting when used by junior medical staff using information obtained on routine clinical assessment. METHODS: This was a prospective cohort study in an acute general medical unit. All patients aged 65 and over admitted to a general medical unit during August and September 2013 were eligible for the study. CFS score at baseline was documented by a member of the treating medical team. Demographic information and outcomes were obtained from medical records. The primary outcomes were functional decline and death within three months. RESULTS: Frailty was assessed in 95 % of 179 eligible patients. 45 % of patients experienced functional decline and 11 % died within three months. 40 % of patients were classified as vulnerable/mildly frail, and 41 % were moderately to severely frail. When patients in residential care were excluded, increasing frailty was associated with functional decline (p = 0.011). Increasing frailty was associated with increasing mortality within three months (p = 0.012). CONCLUSIONS: A high proportion of eligible patients had the frailty measure completed, demonstrating the acceptability of the CFS to clinicians. Despite lack of training for medical staff, increasing frailty was correlated with functional decline and mortality supporting the validity of the CFS as a frailty screening tool for clinicians. PMID- 27250651 TI - Marked Reduction of the Number and Individual Volume of Sebaceous Glands in Psoriatic Lesions. AB - BACKGROUND: Psoriasis is a chronic inflammatory skin disease characterized by plaques with inflammation, infiltration, hyper-/parakeratosis and desquamation. Microscopic findings in previous studies have revealed some degree of atrophy of the sebaceous glands in patients with psoriasis vulgaris and psoriatic alopecia. OBJECTIVE: The aim of this study was to investigate possible changes of the sebaceous glands in patients with psoriatic plaques and especially psoriatic alopecia. METHODS: Histological and stereological analyses were performed in skin specimens from involved and healthy-looking skin of 14 patients with psoriasis. Stereology detects and quantifies 3-dimensional structures ex vivo. Furthermore, the differentiation process of sebocytes of another 14 psoriatic patients was examined by immunohistochemistry of involved and uninvolved skin specimens. RESULTS: A significant reduction of the number of sebaceous glands as well as of the volume of individual sebaceous glands was assessed in the lesional compared to the nonlesional psoriatic skin. Moreover, it was likely that sebocytes in psoriatic lesions may not differentiate properly. CONCLUSION: These findings indicate that the sebaceous gland may be a player and not an innocent bystander in the development of psoriatic lesions and especially of psoriatic alopecia. PMID- 27250652 TI - Growth and palmitoleic acid accumulation of filamentous oleaginous microalgae Tribonema minus at varying temperatures and light regimes. AB - Palmitoleic acid (C16:1Delta9), contributes greatly to human health, industrial chemicals and biodiesel. The filamentous oleaginous microalgae Tribonema sp. has been identified as a highly efficient producer of palmitoleic acid. Temperature and light regime were adapted to regulate the palmitoleic acid content in this study. Strain T. minus was able to grow well at all the tested temperatures, even at 5 degrees C. The optimum temperature for palmitoleic acid accumulation (54.25 % of total fatty acid) was 25 degrees C. Moreover, both light intensity and photoperiod affect the growth, lipid content and fatty acid files of T. minus. The culture exposed to 240 MUmol photons m(-2) s(-1) with a photoperiod of 24:0 showed the highest biomass (6.87 g L(-1)) and biggest lipid content (61.27 % of dry weight), whereas the most amount of palmitoleic acid (50.47 % of total fatty acid) was detected at 120 MUmol photons m(-2) s(-1). These findings make tangible contributions to culture T. minus for commercial production of lipid or palmitoleic acid. PMID- 27250653 TI - Production, characteristics and applications of phytase from a rhizosphere isolated Enterobacter sp. ACSS. AB - Optimization of process parameters for phytase production by Enterobacter sp. ACSS led to a 4.6-fold improvement in submerged fermentation, which was enhanced further in fed-batch fermentation. The purified 62 kDa monomeric phytase was optimally active at pH 2.5 and 60 degrees C and retained activity over a wide range of temperature (40-80 degrees C) and pH (2.0-6.0) with a half-life of 11.3 min at 80 degrees C. The kinetic parameters K m, V max, K cat, and K cat/K m of the pure phytase were 0.21 mM, 131.58 nmol mg(-1) s(-1), 1.64 * 10(3) s(-1), and 7.81 * 10(6) M(-1) s(-1), respectively. The enzyme was fairly stable in the presence of pepsin under physiological conditions. It was stimulated by Ca(+2), Mg(+2) and Mn(+2), but inhibited by Zn(+2), Cu(+2), Fe(+2), Pb(+2), Ba(+2) and surfactants. The enzyme can be applied in dephytinizing animal feeds, and the baking industry. PMID- 27250654 TI - Primary Cilia and Intraflagellar Transport Proteins in Bone and Cartilage. AB - Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of human pleiotropic syndromes called Ciliopathies. Some of the ciliopathies display skeletal dysplasias, implying the important role of primary cilia in skeletal development and homeostasis. Emerging evidence has shown that loss or malfunction of primary cilia or ciliary proteins in bone and cartilage is associated with developmental and function defects. Intraflagellar transport (IFT) proteins are essential for cilia formation and/or function. In this review, we discuss the role of primary cilia and IFT proteins in the development of bone and cartilage, as well as the differentiation and mechanotransduction of mesenchymal stem cells, osteoblasts, osteocytes, and chondrocytes. We also include the role of primary cilia in tooth development and highlight the current advance of primary cilia and IFT proteins in the pathogenesis of cartilage diseases, including osteoarthritis, osteosarcoma, and chondrosarcoma. PMID- 27250655 TI - Developmental Regulation of the Growth Plate and Cranial Synchondrosis. AB - Long bones and the cranial base are both formed through endochondral ossification. Elongation of long bones is primarily through the growth plate, which is a cartilaginous structure at the end of long bones made up of chondrocytes. Growth plate chondrocytes are organized in columns along the longitudinal axis of bone growth. The cranial base is the growth center of the neurocranium. Synchondroses, consisting of mirror-image growth plates, are critical for cranial base elongation and development. Over the last decade, considerable progress has been made in determining the roles of the parathyroid hormone-related protein, Indian hedgehog, fibroblast growth factor, bone morphogenetic protein, and Wnt signaling pathways in various aspects of skeletal development. Furthermore, recent evidence indicates the important role of the primary cilia signaling pathway in bone elongation. Here, we review the development of the growth plate and cranial synchondrosis and the regulation by the above-mentioned signaling pathways, highlighting the similarities and differences between these 2 structures. PMID- 27250656 TI - Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation. AB - Bromobenzene is a well-known environmental toxin which causes liver and kidney damage through CYP450-mediated bio-activation to generate reactive metabolites and, consequently, oxidative stress. The present study aimed to evaluate the possible protective role of withaferin A against bromobenzene-induced liver and kidney damage in mice. Withaferin A (10 mg/kg) was administered orally to the mice for 8 days before intragastric intubation of bromobenzene (10 mmol/kg). As results of this experiment, the levels of liver and kidney functional markers, lipid peroxidation, and cytokines (TNF-alpha and IL-1beta) presented an increase and there was a decrease in anti-oxidant activity in the bromobenzene-treated group of mice. Pre-treatment with withaferin A not only significantly decreased the levels of liver and kidney functional markers and cytokines but also reduced oxidative stress, as evidenced by improved anti-oxidant status. In addition, the mitochondrial dysfunction shown through the decrease in the activities of mitochondrial enzymes and imbalance in the Bax/Bcl-2 expression in the livers and kidneys of bromobenzene-treated mice was effectively prevented by pre administration of withaferin A. These results validated our conviction that bromobenzene caused liver and kidney damage via mitochondrial pathway and withaferin A provided significant protection against it. Thus, withaferin A may have possible usage in clinical liver and kidney diseases in which oxidative stress and mitochondrial dysfunction may be existent. PMID- 27250658 TI - Non-sedation versus sedation with a daily wake-up trial in critically ill patients recieving mechanical ventilation - effects on long-term cognitive function: Study protocol for a randomized controlled trial, a substudy of the NONSEDA trial. AB - BACKGROUND: The effects of non-sedation on cognitive function in critically ill patients on mechanical ventilation are not yet certain. This trial is a substudy of the NONSEDA trial where critically ill patients are randomized to non-sedation or to sedation with a daily wake-up attempt during mechanical ventilation in the intensive care unit (ICU). The aim of this substudy is to assess the effects of non-sedation versus sedation with a daily wake-up attempt on long-term cognitive function. METHODS: This is an investigator-initiated, randomized, clinical, parallel-group, superiority trial, including 200 patients. Inclusion criteria will be adult patients who are intubated and on mechanical ventilation with an expected duration of more than 24 hours. Exclusion criteria will be patients who are comatose at admission and patients with conditions requiring therapeutic coma (i.e., severe head trauma, status epilepticus, patients treated with therapeutic hypothermia and patients with severe hypoxia). The experimental intervention will be non-sedation supplemented with pain management during mechanical ventilation. The control intervention will be sedation with a daily wake-up attempt. The primary outcome will be cognitive function 3 months after discharge from intensive care. The secondary outcomes will be the results of seven specific cognitive tests, performed 3 months after discharge from intensive care, and the association between hypoactive and agitated delirium during ICU admission and long-term cognitive function. DISCUSSION: If non-sedation can improve long-term cognitive function, it could be an approach worth considering for a larger group of critically ill patients. TRIAL REGISTRATION: The study has been approved by the relevant scientific ethics committee and is registered at ClinicalTrials.gov (ID: NCT02035436 , registered on 10 January 2014). PMID- 27250657 TI - Upregulation of long noncoding RNA SPRY4-IT1 promotes metastasis of esophageal squamous cell carcinoma via induction of epithelial-mesenchymal transition. AB - Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. In the present study, we find that the expression of lncRNA SPRY4-IT1 is significantly upregulated in ESCC cell lines as compared with human esophageal epithelial cell line HEEC. Overexpression of SPRY4-IT1 can increase in vitro motility of ESCC cells via induction of epithelial-mesenchymal transition (EMT), which is characterized by increasing the expression of vimentin (Vim) and fibronectin (FN) with a concomitant decrease of E-cadherin (E-Cad) and ZO-1, while silencing of SPRY4-IT1 significantly inhibits the in vitro motility of ESCC cells. Further, the knockdown of SPRY4-IT1 also significantly attenuates TFG-beta-induced EMT of ESCC cells. Further, lncRNA SPRY4-IT1 can directly increase the transcription, expression, and nuclear localization of Snail, one key transcription factor during the EMT processes of cancer cells, while siRNA mediated specific knockdown of Snail can significantly attenuate SPRY4-IT1 induced EMT of ESCC cells. Our results suggest that lncRNA SPRY4-IT1 might be considered as a novel oncogene involved in ESCC progression. PMID- 27250660 TI - A novel laser-collider used to produce monoenergetic 13.3 MeV (7)Li (d, n) neutrons. AB - Neutron energy is directly correlated with the energy of the incident ions in experiments involving laser-driven nuclear reactions. Using high-energy incident ions reduces the energy concentration of the generated neutrons. A novel "laser collider" method was used at the Shenguang II laser facility to produce monoenergetic neutrons via (7)Li (d, n) nuclear reactions. The specially designed K-shaped target significantly increased the numbers of incident d and Li ions at the keV level. Ultimately, 13.3 MeV neutrons were obtained. Considering the time resolution of the neutron detector, we demonstrated that the produced neutrons were monoenergetic. Interferometry and a Multi hydro-dynamics simulation confirmed the monoenergetic nature of these neutrons. PMID- 27250661 TI - Mycothiol protects Corynebacterium glutamicum against acid stress via maintaining intracellular pH homeostasis, scavenging ROS, and S-mycothiolating MetE. AB - Mycothiol (MSH) plays a major role in protecting cells against oxidative stress and detoxification from a broad range of exogenous toxic agents. In the present study, we reveal that intracellular MSH contributes significantly to the adaptation to acidic conditions in the model organism Corynebacterium glutamicum. We present evidence that MSH confers C. glutamicum with the ability to adapt to acidic conditions by maintaining pHi homeostasis, scavenging reactive oxygen species (ROS), and protecting methionine synthesis by the S-mycothiolation modification of methionine synthase (MetE). The role of MSH in acid adaptation was further confirmed by improving the acid tolerance of C. glutamicum by overexpressing the key MSH synthesis gene mshA. Hence, our work provides insights into a previously unknown, but important, aspect of the C. glutamicum cellular response to acid stress. The results reported here may help to understand acid tolerance mechanisms in acid sensitive bacteria and may open a new avenue for improving acid resistance in industry strains for the production of bio-based chemicals from renewable biomass. PMID- 27250662 TI - A tightly inducible riboswitch system in Synechocystis sp. PCC 6803. AB - Cyanobacteria are photosynthetic microorganisms that serve as experimental model organisms for the study of photosynthesis, environmental stress responses, and the production of biofuels. Genetic tools for bioengineering have been developed as a result of such studies. However, there is still room for improvement for the tight control of experimental protein expression in these microorganisms. Here, we describe an expression system controlled by a theophylline-responsive riboswitch that we have constructed in the cyanobacterium Synechocystis sp. PCC 6803. We demonstrate that, in response to different theophylline concentrations, this riboswitch can tightly control green fluorescence protein expression in Synechocystis. Thus, this system is useful as a tool for genetic engineering and the synthetic biology of cyanobacteria. PMID- 27250663 TI - Nitrile-synthesizing enzyme: Screening, purification and characterization. AB - Cyanide is known as a toxic compound for almost all living organisms. We have searched for cyanide-resistant bacteria from the soil and stock culture collection of our laboratory, and have found the existence of a lot of microorganisms grown on culture media containing 10 mM potassium cyanide. Almost all of these cyanide-resistant bacteria were found to show beta-cyano-L-alanine (beta-CNAla) synthetic activity. beta-CNAla synthase is known to catalyze nitrile synthesis: the formation of beta-CNAla from potassium cyanide and O-acetyl-L serine or L-cysteine. We found that some microorganisms were able to detoxify cyanide using O-methyl-DL-serine, O-phospho-L-serine and beta-chloro-DL-alanine. In addition, we purified beta-CNAla synthase from Pseudomonas ovalis No. 111 in nine steps, and characterized the purified enzyme. This enzyme has a molecular mass of 60,000 and appears to consist of two identical subunits. The purified enzyme exhibits a maximum activity at pH 8.5-9.0 at an optimal temperature of 40 50 degrees C. The enzyme is specific for O-acetyl-L-serine and beta-chloro-DL alanine. The Km value for O-acetyl-L-serine is 10.0 mM and Vmax value is 3.57 MUmol/min/mg. PMID- 27250664 TI - Nitrile-synthesizing enzyme: Gene cloning, overexpression and application for the production of useful compounds. AB - One of the nitrile-synthesizing enzymes, beta-cyano-L-alanine synthase, catalyzes beta-cyano-L-alanine (beta-CNAla) from potassium cyanide and O-acetyl-L-serine or L-cysteine. We have identified this enzyme from Pseudomonas ovalis No. 111. In this study, we cloned the beta-CNAla synthase gene and expressed it in Escherichia coli and Rhodococcus rhodochrous. Furthermore, we carried out co expression of beta-CNAla synthase with nitrilase or nitrile hydratases in order to synthesize aspartic acid and asparagine from KCN and O-acetyl-L-serine. This strategy can be used for the synthesis of labeled amino acids by using a carbon labeled KCN as a substrate, resulting in an application for positron emission tomography. PMID- 27250665 TI - Charge carrier loss mechanisms in CuInS2/ZnO nanocrystal solar cells. AB - Heterojunction solar cells based on colloidal nanocrystals (NCs) have shown remarkable improvements in performance in the last decade, but this progress is limited to merely two materials, PbS and PbSe. However, solar cells based on other material systems such as copper-based compounds show lower power conversion efficiencies and much less effort has been made to develop a better understanding of factors limiting their performance. Here, we study charge carrier loss mechanisms in solution-processed CuInS2/ZnO NC solar cells by combining steady state measurements with transient photocurrent and photovoltage measurements. We demonstrate the presence of an extraction barrier at the CuInS2/ZnO interface, which can be reduced upon illumination with UV light. However, trap-assisted recombination in the CuInS2 layer is shown to be the dominant decay process in these devices. PMID- 27250666 TI - Why do occupational therapists' medico-legal opinions differ regarding the amount of domestic assistance a person requires? PMID- 27250668 TI - In this June issue. PMID- 27250669 TI - Human factors in the emergency department: Is physician perception of time to intubation and desaturation rate accurate? AB - OBJECTIVE: The main objective of the present study was to examine the perceived versus actual time to intubation (TTI) as an indication to help determine the situational awareness of Emergency Physicians during rapid sequence intubation and, additionally, to determine the physician's perception of desaturation events. METHODS: A timed, observation prospective cohort study was conducted. A post-intubation survey was administered to the intubating physician. Each step of the procedure was timed by an observer in order to determine actual TTI. The number of desaturation events was also recorded. RESULTS: One hundred individual intubations were included. The provider perceived TTI was significantly different and underestimated when compared with the actual TTI (23 s, 95% confidence interval (CI) 20.4-25.49 vs 45.5 s, 95% CI 40.2-50.7, P < 0.001, respectively). Pearson correlation coefficient of perceived TTI to actual TTI was r(2) = 0.39 (95% CI 0.21-0.54, P < 0.001). The provider perceived desaturation rate was also significantly different from actual desaturation rate (13, 95% CI 3-12 vs 23, 95% CI 13-29, P = 0.05, respectively). The overall time to desaturation was 65.1 s. CONCLUSIONS: Our findings have shown that provider's perception of TTI occurs sooner than actually observed. Also, the providers were less aware of desaturation during the procedure. PMID- 27250670 TI - Estimation of the potential eye and tissue donor pool in an Australian emergency department. AB - OBJECTIVE: EDs have long been considered a potential source of eye and tissue donors, but no specific evidence to support this was identified in the Australian setting. The present study aims to bridge that knowledge gap, by analysing medical and social histories of those who have died over a 5 year period so as to determine donation eligibility in this population. METHODS: A retrospective audit was undertaken of all patients who died within the Royal Melbourne Hospital ED between 2010 and 2014. ED records, pharmacy records and electronic medical histories were audited for the presence of eye and tissue donation exclusion criteria and the distribution of these criteria within the target population. RESULTS: Over the 5 year period, of 326 deaths that occurred in the ED, one third was suitable for eye donation (n = 106) and one in seven (n = 45) for tissue donation. Of the age appropriate patients, five criteria were identified that excluded up to 85% of the population not eligible to donate. These were: haematological malignancies, neurodegenerative conditions, non-haematological malignancies, chronic renal failure and eye disease. CONCLUSION: The present study has identified a large pool of potential eye and tissue donors; a pool mostly unrecognised by emergency clinicians. An extensive list of exclusion criteria restricts donor potential. However, the present study has identified that only five fundamentally limit donation in the ED population. Utilisation of this knowledge will allow for the development of clinical triggers that will improve identification, and increase realisation, of potential donors. PMID- 27250671 TI - Review of therapeutic agents employed by an Australian aeromedical prehospital and retrieval service. AB - OBJECTIVE: There is little current evidence regarding which therapeutic agents are actually used within existing aeromedical services. The Greater Sydney Area Helicopter Emergency Medical Service operates a large, physician-staffed, multimodal, prehospital and interhospital retrieval service. The aim of the present study was to identify the range and frequency of drug, fluid and blood product use within our service. METHODS: This was a retrospective cross-sectional study. Case sheets relating to a 12 month period were inspected to identify the therapeutic agents used by retrieval teams during each mission. Corresponding case notes, demographic data (age, sex) and case data (prehospital vs interhospital, trauma vs medical) were extracted from an electronic database. RESULTS: Of 2566 missions, 848 were prehospital, 1662 interhospital and 56 mixed. Prehospital missions were associated with fewer agents per case (median, 2 vs 3) and a narrower range of agents overall (45 vs 117) compared to interhospital missions. In both mission types, the most frequently used agents included morphine, fentanyl, Hartmann's solution, ketamine, rocuronium, ondansetron and midazolam. Noradrenaline, propofol and metaraminol were used frequently in interhospital missions only. A number of stocked and unstocked agents were used less commonly, or not at all, over the study period. CONCLUSIONS: The results of the present study form a practical guide to aid prehospital and retrieval services in establishing or reviewing their medical agent formularies. Key practice points illuminated by the data provide insights into current practice in critical care. There remains a clear need for similar studies from other services worldwide. PMID- 27250673 TI - Concise Review: Application of In Vitro Transcribed Messenger RNA for Cellular Engineering and Reprogramming: Progress and Challenges. AB - Several diseases are caused by missing or defective synthesis of proteins due to genetic or acquired disorders. In recent years, in vitro transcribed (IVT) messenger RNA (mRNA)-based therapy for de novo protein expression in cells has increased in importance. Thereby, desired proteins can be produced in cells by exogenous delivery of IVT mRNA, which does not integrate into the host genome and results in transient production of target proteins. Due to the lack of genomic integration, the risk of mutation and tumor development is minimized. Different approaches using IVT mRNA have been applied to alter the expression profiles of cells by the production of proteins. IVT mRNAs encoding transcription factors have led to the highly efficient induction of pluripotency in somatic cells and generated induced pluripotent stem cells that are free of viral vector components. Furthermore, specific IVT mRNA cocktails containing more than one specific IVT mRNA can be used to directly induce the differentiation into a desired cell type. In theory, every desired mRNA can be produced in vitro and used to enable extrinsic biosynthesis of target proteins in each cell type. Cells can be engineered by IVT mRNA to express antigens on dendritic cells for vaccination and tumor treatment, surface receptors on stem cells for increased homing to distinct areas, and to produce industrial grade human growth factors. In this review, we focus on the progress and challenges in mRNA-based cell engineering approaches. Stem Cells 2017;35:68-79. PMID- 27250674 TI - Use of bioartificial dermal regeneration template for skin restoration in combat casualty injuries. AB - A letter in response to: Seavey JG, Masters ZA, Balazs GC, Tintle SM, Sabino J, Fleming ME & Valerio IL. Use of bioartificial dermal regeneration template for skin restoration in combat casualty injuries. Regen. Med. 11(1), 81-90 (2016). PMID- 27250675 TI - Light accelerates plant responses to warming. AB - Competition for light has profound effects on plant performance in virtually all terrestrial ecosystems. Nowhere is this more evident than in forests, where trees create environmental heterogeneity that shapes the dynamics of forest-floor communities(1-3). Observational evidence suggests that biotic responses to both anthropogenic global warming and nitrogen pollution may be attenuated by the shading effects of trees and shrubs(4-9). Here we show experimentally that tree shade is slowing down changes in below-canopy communities due to warming. We manipulated levels of photosynthetically active radiation, temperature and nitrogen, alone and in combination, in a temperate forest understorey over a 3 year period, and monitored the composition of the understorey community. Light addition, but not nitrogen enrichment, accelerated directional plant community responses to warming, increasing the dominance of warmth-preferring taxa over cold-tolerant plants (a process described as thermophilization(6,10-12)). Tall, competitive plants took greatest advantage of the combination of elevated temperature and light. Warming of the forest floor did not result in strong community thermophilization unless light was also increased. Our findings suggest that the maintenance of locally closed canopy conditions could reduce, at least temporarily, warming-induced changes in forest floor plant communities. PMID- 27250676 TI - Forest ecology: Conservation through closure. PMID- 27250677 TI - A trehalose-6-phosphate phosphatase enhances anaerobic germination tolerance in rice. AB - Global socioeconomic developments create strong incentives for farmers to shift from transplanted to direct-seeded rice (DSR) as a means of intensification and economization(1). Rice production must increase to ensure food security(2) and the bulk of this increase will have to be achieved through intensification of cultivation, because expansion of cultivated areas is reaching sustainable limits(3). Anaerobic germination tolerance, which enables uniform germination and seedling establishment under submergence(4), is a key trait for the development of tropical DSR varieties(5,6). Here, we identify a trehalose-6-phosphate phosphatase gene, OsTPP7, as the genetic determinant in qAG-9-2, a major quantitative trait locus (QTL) for anaerobic germination tolerance(7). OsTPP7 is involved in trehalose-6-phosphate (T6P) metabolism, central to an energy sensor that determines anabolism or catabolism depending on local sucrose availability(8,9). OsTPP7 activity may increase sink strength in proliferating heterotrophic tissues by indicating low sugar availability through increased T6P turnover, thus enhancing starch mobilization to drive growth kinetics of the germinating embryo and elongating coleoptile, which consequently enhances anaerobic germination tolerance. PMID- 27250678 TI - Crystal structure of the catalytic subunit of magnesium chelatase. AB - Tetrapyrroles, including haem and chlorophyll, play vital roles for various biological processes, such as respiration and photosynthesis, and their biosynthesis is critical for virtually all organisms. In photosynthetic organisms, magnesium chelatase (MgCh) catalyses insertion of magnesium into the centre of protoporphyrin IX, the branch-point precursor for both haem and chlorophyll, leading tetrapyrrole biosynthesis into the magnesium branch(1,2). This reaction needs a cooperated action of the three subunits of MgCh: the catalytic subunit ChlH and two AAA(+) subunits, ChlI and ChlD (refs 3-5). To date, the mechanism of MgCh awaits further elucidation due to a lack of high resolution structures, especially for the ~150 kDa catalytic subunit. Here we report the crystal structure of ChlH from the photosynthetic cyanobacterium Synechocystis PCC 6803, solved at 2.5 A resolution. The active site is buried deeply inside the protein interior, and the surrounding residues are conserved throughout evolution. This structure helps to explain the loss of function reported for the cch and gun5 mutations of the ChlH subunit, and to provide the molecular basis of substrate channelling during the magnesium-chelating process. The structure advances our understanding of the holoenzyme of MgCh, a metal chelating enzyme other than ferrochelatase. PMID- 27250679 TI - Kinesin motors: Teamsters' union. PMID- 27250680 TI - Chromatin assembly factor CAF-1 represses priming of plant defence response genes. AB - Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter with a pathogen. Because activation of defence responses has a fitness cost, priming must be tightly controlled to prevent spurious activation of defence. However, mechanisms that repress defence gene priming are poorly understood. Here, we show that the histone chaperone CAF-1 is required to establish a repressed chromatin state at defence genes. Absence of CAF-1 results in spurious activation of a salicylic acid-dependent pathogen defence response in plants grown under non-sterile conditions. Chromatin at defence response genes in CAF-1 mutants under non-inductive (sterile) conditions is marked by low nucleosome occupancy and high H3K4me3 at transcription start sites, resembling chromatin in primed wild-type plants. We conclude that CAF-1-mediated chromatin assembly prevents the establishment of a primed state that may under standard non sterile growth conditions result in spurious activation of SA-dependent defence responses and consequential reduction of plant vigour. PMID- 27250681 TI - Calcium signalling mediates self-incompatibility response in the Brassicaceae. AB - Self-incompatibility in the Brassicaceae is controlled by multiple haplotypes encoding the pollen ligand (S-locus protein 11, SP11, also known as S-locus cysteine-rich protein, SCR) and its stigmatic receptor (S-receptor kinase, SRK). A haplotype-specific interaction between SP11/SCR and SRK triggers the self incompatibility response that leads to self-pollen rejection, but the signalling pathway remains largely unknown. Here we show that Ca(2+) influx into stigma papilla cells mediates self-incompatibility signalling. Using self-incompatible Arabidopsis thaliana expressing SP11/SCR and SRK, we found that self-pollination specifically induced an increase in cytoplasmic Ca(2+) ([Ca(2+)]cyt) in papilla cells. Direct application of SP11/SCR to the papilla cell protoplasts induced Ca(2+) increase, which was inhibited by D-(-)-2-amino-5-phosphonopentanoic acid (AP-5), a glutamate receptor channel blocker. An artificial increase in [Ca(2+)]cyt in papilla cells arrested wild-type (WT) pollen hydration. Treatment of papilla cells with AP-5 interfered with self-incompatibility, and Ca(2+) increase on the self-incompatibility response was reduced in the glutamate receptor-like channel (GLR) gene mutants. These results suggest that Ca(2+) influx mediated by GLR is the essential self-incompatibility response leading to self-pollen rejection. PMID- 27250682 TI - Self-incompatibility: Calcium signalling in Brassica. PMID- 27250683 TI - Photosynthesis: Getting it together for CO2 fixation. PMID- 27250684 TI - 150 years of an integrative plant physiology. PMID- 27250685 TI - Stomata signalling: A pore within a pore. PMID- 27250687 TI - Barley domestication: Double event. PMID- 27250686 TI - Evolution: Dryland orchid divergence. PMID- 27250688 TI - Treasuring researchers. PMID- 27250689 TI - Pre-40S ribosome biogenesis factor Tsr1 is an inactive structural mimic of translational GTPases. AB - Budding yeast Tsr1 is a ribosome biogenesis factor with sequence similarity to GTPases, which is essential for cytoplasmic steps in 40S subunit maturation. Here we present the crystal structure of Tsr1 at 3.6 A. Tsr1 has a similar domain architecture to translational GTPases such as EF-Tu and the selenocysteine incorporation factor SelB. However, active site residues required for GTP binding and hydrolysis are absent, explaining the lack of enzymatic activity in previous analyses. Modelling of Tsr1 into cryo-electron microscopy maps of pre-40S particles shows that a highly acidic surface of Tsr1 is presented on the outside of pre-40S particles, potentially preventing premature binding to 60S subunits. Late pre-40S maturation also requires the GTPase eIF5B and the ATPase Rio1. The location of Tsr1 is predicted to block binding by both factors, strongly indicating that removal of Tsr1 is an essential step during cytoplasmic maturation of 40S ribosomal subunits. PMID- 27250690 TI - Modelling and numerical simulation of the in vivo mechanical response of the ascending aortic aneurysm in Marfan syndrome. AB - Marfan syndrome (MFS) is a genetic disorder that affects connective tissue, impairing cardiovascular structures and function, such as heart valves and aorta. Thus, patients with Marfan disease have a higher risk of developing circulatory problems associated with mitral and aortic valves prolapse, manifested as dilated aorta and aortic aneurysm. However, little is known about the biomechanical characteristics of these structures affected with MFS. This study presents the modelling and simulation of the mechanical response of human ascending aortic aneurysms in MFS under in vivo conditions with intraluminal pressures within normotensive and hypertensive ranges. We obtained ascending aortic segments from five adults with MFS subjected to a vascular prosthesis implantation replacing an aortic aneurysm. We characterised the arterial samples via ex vivo tensile test measurements that enable fitting the material parameters of a hyperelastic isotropic constitutive model. Then, these material parameters were used in a numerical simulation of an ascending aortic aneurysm subjected to in vivo normotensive and hypertensive conditions. In addition, we assessed different constraints related to the movement of the aortic root. Overall, our results provide not only a realistic description of the mechanical behaviour of the vessel, but also useful data about stress/stretch-based criteria to predict vascular rupture. This knowledge may be included in the clinical assessment to determine risk and indicate surgical intervention. PMID- 27250691 TI - Calcaneal varus angle change in normal calcaneus: a three-dimensional finite element analysis. AB - The objective of the study was to investigate the stress changes in the posterior articular surface of the calcaneus following alternation of the calcaneal varus angle in normal calcaneus and discuss the clinical significance of the calcaneal varus angle. Axial view radiographs of 165 volunteers were obtained to measure the calcaneal varus angle of normal calcaneus. A calcaneal model with different varus angle changes (including +2 degrees , +4 degrees , +6 degrees , -2 degrees , -4 degrees , and -6 degrees ) was established using Creo 2.0 software. Stress changes at different calcaneal varus angles in the posterior articular surface of the calcaneus under a load of 100 N were measured. Stressed areas in posterior articular facets were slightly fewer following +2 degrees , +4 degrees , and +6 degrees changes in varus angle than in normal varus angles with stress concentering regions moving to the anteromedial aspect of the posterior calcaneal facet. However, stress concentering areas in posterior calcaneal facets following -4 degrees and -6 degrees changes in varus angle obviously moved to the anterior and posterior medial side of posterior calcaneal facets. Stress distribution in the posterior articular surface of the calcaneus varies with the calcaneal varus angle. The decrease in calcaneal varus angle following operative treatment of calcaneal fractures should be controlled within 2 degrees . PMID- 27250692 TI - High Frequency of Hb E-Saskatoon (HBB: c.67G > A) in Brazilians: A New Genetic Origin? AB - Hb E-Saskatoon [beta22(B4)Glu->Lys, HBB: c.67G > A] is a rare, nonpathological beta-globin variant that was first described in a Canadian woman of Scottish and Dutch ancestry and has since then been detected in several populations. The aim of the present study was to identify the origin of Hb E-Saskatoon in Brazil using beta-globin haplotypes and genetic ancestry in carriers of this hemoglobin (Hb) variant. Blood samples were investigated by isoelectric focusing (IEF) and high performance liquid chromatography (HPLC) using commercial kits. Hb E-Saskatoon was confirmed by amplification of the HBB gene, followed by sequence analysis. Haplotypes of the beta-globin gene were determined by polymerase chain reaction (PCR), followed by digestion with specific restriction enzymes. Individual ancestry was estimated with 48 biallelic insertion/deletions using three 16-plex PCR amplifications. The IEF pattern was similar to Hbs C (HBB: c.19G > A) and Hb E (HBB: c.79G > A) [isoelectric point (pI): 7.59-7.65], and HPLC results showed an elution in the Hb S (HBB: c.20A > T) window [retention time (RT): 4.26-4.38]. DNA sequencing of the amplified beta-globin gene showed a mutation at codon 22 (GAA>AAA) corresponding to Hb E-Saskatoon. A total of 11 cases of this variant were identified. In nine unrelated individuals, Hb E-Saskatoon was in linkage disequilibrium with haplotype 2 [+ - - - -]. All subjects showed a high degree of European contribution (mean = 0.85). Hb E-Saskatoon occurred on the beta-globin gene of haplotype 2 in all Brazilian carriers. These findings suggest a different genetic origin for this Hb variant from that previously described. PMID- 27250693 TI - Usefulness of triphasic CT aortic angiography in acute and surveillance: Our experience in the assessment of acute aortic dissection and endoleak. AB - INTRODUCTION: Computed tomography angiography (CTA) has been widely used in the diagnostic evaluation of many aortic diseases, but no standardized techniques actually exist for aortic CTA. The aim of this study was to describe the usefulness of triphasic CTA in aortic assessment in both non-traumatic emergency and surveillance conditions. METHODS: We performed non ECG-gated CTA examinations with a 64-slice CT scanner using a triphasic protocol consisting of an unenhanced acquisition, and two (early and delayed) contrastographic phases with a delay of 25-30 s and 100-120 s respectively after the injection of contrast medium. Were retrospectively selected adult patients with imaging findings of acute aortic dissection (AAD) or endoleak (EL) from November 2012 to November 2014. RESULTS: AAD was detected in 36 (67%) patients: 23 type A-AADs, and 13 type B-AADs. The presence of EL was observed in 18 (33%) patients: 1 type Ia, 5 types IIa, 2 types IIb, 1 type IIIa and 9 types IIIb. DISCUSSION: Triphasic CTA is useful to provide correct and prompt diagnosis of AAD in emergency, allowing the evaluation of type and atypical forms of AAD, and the identification of possible branch-vessel involvement and complications. During surveillance, triphasic CTA assures accurate and complete assessment of all known and unknown ELs and it is essential for first follow-up examination. CONCLUSION: Triphasic CTA represents a reliable imaging tool for aortic assessment in both non-traumatic emergency and surveillance after endovascular aneurysm repair. Modified protocol could be employed in selected patients and tailored in their known disease. PMID- 27250694 TI - The impact of BMI on early colorectal neoplastic lesions and the role of endoscopic diagnosis:. An Italian observational study. AB - INTRODUCTION: CRC often arises from polyps: an early detection and resection are effective in decreasing both incidence and mortality rate. Relation between risk factors, adenomas and CRC have been showed, but there is little evidence for overweight association with preneoplastic lesions. This study analyzed the correlation between body mass index (BMI) and primitive site of polyps. METHODS: We performed a retrospective study, in a period between January 2010 and October 2014. Subjects aged 50 years and older who underwent their first-time screening colonoscopy were included. Reports regarding characteristic of the polyps were collected. RESULTS: 142 patients were enrolled and they were divided into two groups: group I - patients with left sided colonic polyps, and group II - patients who right sided colonic polyps. The ANOVA test-one way, documents a difference between the BMI and the colon localization of polyps. CONCLUSIONS: Patients with overweight had a higher risk to develop lesions in the left colon compared to patients with normal weight. Despite the fact that Italian epidemiological studies have found a prevalence of polyps of 44-53% in rectal sigmoid segment, 32-36% in transverse segment and of 14-20% in right segment, we showed an incidence of 26.05% for right sided polyps, which maybe related with the eating habits of the territory. PMID- 27250695 TI - Molecular and phenotypic spectrum of ASPM-related primary microcephaly: Identification of eight novel mutations. AB - Autosomal recessive primary microcephaly (MCPH) is an abnormal proliferation of neurons during brain development that leads to a small brain size but architecturally normal in most instances. Mutations in the ASPM gene have been identified to be the most prevalent. Thirty-seven patients from 30 unrelated families with a clinical diagnosis of MCPH were enrolled in this study. Screening of ASPM gene mutations was performed by targeted linkage analysis followed by direct sequencing. Thirteen protein truncating mutations of the ASPM were identified in 15 families (50%), eight of which were novel mutations. The mutations detected were eight nonsense, four frameshift, and one splice site. Two of these mutations (p.R1327* and p.R3181*) were recurrent and shared similar haplotypes suggesting founder effect. Patients with ASPM mutations had mild to severe intellectual disability and variable degrees of simplified gyral pattern and small frontal lobe. In addition, hypoplasia of corpus callosum (18 patients), mildly small cerebellar vermis (10 patients), and relatively small pons (13 patients) were found in 85.7%, 47.6%, and 61.9%, respectively. Furthermore, one patient had porencephaly and another had a small midline cyst. Epilepsy was documented in two patients (9.5%). Non-neurologic abnormalities consisted of growth retardation (four patients), and co-incidental association of oculo cutaneous albinism (one patient). Our study expands the mutation spectrum of ASPM. Moreover, the simplified gyral pattern and small frontal lobe together with hypoplastic corpus callosum, small cerebellum and pons enable ASPM mutated patients to be distinguished. (c) 2016 Wiley Periodicals, Inc. PMID- 27250696 TI - Improving outcomes in hidradenitis suppurativa. PMID- 27250697 TI - Pain and hospital admissions are important factors associated with quality of life in nonambulatory children. AB - AIM: This was the first study to investigate the factors associated with health related quality of life (HRQoL) in nonambulatory children with cerebral palsy (CP), based on a HRQoL measure specifically developed for this population. METHODS: The Dutch version of the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD-DV) was used to measure HRQoL. It was completed by 66 parents of 47 boys and 19 girls with nonambulatory CP aged between five and 18 years with gross motor function classification system (GMFCS) levels of IV and V. Factors measured were the child's motor and cognitive impairments, comorbidities, pain, parents' education and occupations and family structure. Multiple linear regression analyses were used to determine the significant factors and the relative contribution of these factors to the CPCHILD-DV scores. RESULTS: The most important factors associated with poorer HRQoL scores were pain and hospital admissions in the previous six months. Other factors were as follows: increased GMFCS level, feeding by gastrostomy tube, inability to communicate verbally, cognitive impairment, poor seizure control and higher parents' educational qualifications. CONCLUSION: Pain and hospital admissions were the most important factors that were negatively associated with HRQoL in nonambulatory children with CP between five to 18 years. PMID- 27250698 TI - The freshwater artisanal fishery of Patos Lagoon. AB - In this study data relative to the fishery in the freshwater area of the Patos Lagoon are analysed, and the dynamics, fishing gears used and catches evaluated. The results reveal the existence of two fishery strategies: forbidden mesh size gillnets (FMG; <35 mm; square measure) and allowed mesh size gillnets (AMG; >=35 mm; square measure). In total, 31 species were caught (AMG = 27 and FMG = 24), but selectivity due to mesh size was significant (P < 0.001). The FMG may be very harmful since it captures individuals of most species below size at first maturity, including the target species, the armoured catfish Loricariichthys anus (61% of the total catch). In addition, this gear is used throughout the year, including the closed season (CS; November to January), when the target species is reproducing. Target species for the AMG are larger in size, comprising mainly the mullet Mugil liza, the marine catfish Genidens barbus and the whitemouth croaker Micropogonias furnieri. AMS gillnets were not used during the CS. The use of FMG reveals the need for effective fishery law enforcement and the need for additional studies to assess the status of populations of the exploited species. PMID- 27250699 TI - Embryological Consideration of Dural Arteriovenous Fistulas. AB - The topographical distribution of dural arteriovenous fistulas (DAVFs) was analyzed based on the embryological anatomy of the dural membrane. Sixty-six consecutive cases of intracranial and spinal DAVFs were analyzed based on the angiography, and each shunt point was identified according to the embryological bony structures. The area of dural membranes was categorized into three different groups: a ventral group located on the endochondral bone (VE group), a dorsal group located on the membranous bone (DM group) and a falco-tentorial group (FT group) located in the falx cerebri, tentorium cerebelli, falx cerebelli, and diaphragm sellae. The FT group was designated when the dural membrane was formed only with the dura propria (meningeal layer of the dura mater) and not from the endosteal dura. Cavernous sinus, sigmoid sinus, and anterior condylar confluence was categorized to VE group, which had a female predominance, more benign clinical presentations, and a lower rate of cortical and spinal venous reflux. Transverse sinus, confluence, and superior sagittal sinus belonged to the DM group. Olfactory groove, falx, tent of the cerebellum, and nerve sleeve of spinal cord were categorized to the FT group, which presented later in life and which had a male predominance, more aggressive clinical presentations, and significant cortical and spinal venous reflux. The DAVFs was associated with the layers of the dural membrane characterized by the two different embryological bony structures. The FT group was formed only with the dura propria as an independent risk factor for aggressive clinical course and hemorrhage of DAVFs. PMID- 27250700 TI - Developmental Venous Anomaly: Benign or Not Benign. AB - Developmental venous anomalies (DVAs), previously called venous angiomas, are the most frequently encountered cerebral vascular malformations. However, DVA is considered to be rather an extreme developmental anatomical variation of medullary veins than true malformation. DVAs are composed of dilated medullary veins converging centripetally into a large collecting venous system that drains into the superficial or deep venous system. Their etiology and mechanism are generally accepted that DVAs result from the focal arrest of the normal parenchymal vein development or occlusion of the medullary veins as a compensatory venous system. DVAs per se are benign and asymptomatic except for under certain unusual conditions. The pathomechanisms of symptomatic DVAs are divided into mechanical, flow-related causes, and idiopathic. However, in cases of DVAs associated with hemorrhage, cavernous malformations (CMs) are most often the cause rather than DVAs themselves. The coexistence of CM and DVA is common. There are some possibilities that DVA affects the formation and clinical course of CM because CM related to DVA is generally located within the drainage territory of DVA and is more aggressive than isolated CM in the literature. Brain parenchymal abnormalities surrounding DVA and cerebral varix have also been reported. These phenomena are considered to be the result of venous hypertension associated with DVAs. With the advance of diagnostic imagings, perfusion study supports this hypothesis demonstrating that some DVAs have venous congestion pattern. Although DVAs should be considered benign and clinically silent, they can have potential venous hypertension and can be vulnerable to hemodynamic changes. PMID- 27250704 TI - Closing the gap in Aboriginal women's reproductive health: some progress, but still a long way to go. PMID- 27250703 TI - Dengue Specific Immunoglobulin A Antibody is Present in Urine and Associated with Disease Severity. AB - The kinetics of dengue virus (DENV)-specific IgA antibody in urine and the potential correlation with disease severity remain elusive. In this study, 262 serial urine samples from 78 laboratory-confirmed patients were assayed by a commercial immunoglobulin A (IgA) kit against DENV. All cases were classified into dengue fever (DF) and severe dengue (SD) according to the 2009 WHO/TDR guideline. The total positive rate of IgA in urine was 59%. DENV-specific IgA was detected in urine from day 2 to day 13 after the onset of illness in DF patients; While for SD patients, anti-DENV IgA could be detected till day 14. The positive rate of IgA in patients with secondary infection was higher than that in patients with primary infection. Importantly, during 4-7 days after the onset of illness, the IgA positive rate of SD patients was significantly higher than that of DF patients. Especially, the intensity of IgA signal in SD patients was obviously stronger than that in DF patient at the recovery stage. Overall, our results suggested that the existence of DENV-specific IgA antibodies in urine might be a warning sign for the severity of disease and its measurement might provide valuable guidance for proper patient management. PMID- 27250705 TI - Fetal autopsy and closing the gap. AB - Over the past 30 years, the perinatal mortality rate (PMR) in Australia has been reduced to almost a quarter of that observed in the 1970s. To a large extent, this decline in the PMR has been driven by a reduction in neonatal mortality. Stillbirth rates have, however, remained relatively unchanged, and stillbirth rates for Aboriginal or Torres Strait Islander mothers have remained approximately twice that for non-Indigenous women over the last 10 years. The causes for this difference remain to be fully established. Fetal autopsy is the single most important investigative tool to determine the cause of fetal demise. While facilitators and barriers to gaining consent for autopsy have been identified in a non-Indigenous context, these are yet to be established for Indigenous families. In order to address the gap in stillbirths between Indigenous and non-Indigenous mothers, it is essential to identify culturally appropriate ways when approaching Aboriginal and Torres Strait Islander families for consent after fetal death. Culturally safe and appropriate counselling at this time provides the basis for respectful care to families while offering an opportunity to gain knowledge to reduce the PMR. Identifying the cause of preventable stillbirth is an important step in narrowing the disparity in stillbirth rates between Indigenous and non-Indigenous mothers. PMID- 27250706 TI - Growth Factor-Free Pre-vascularization of Cell Sheets for Tissue Engineering. AB - The therapeutic efficacy of tissue-engineered constructs is often compromised by inadequate inosculation and neo-vascularization. This problem is considered one of the biggest hurdles in the field and finding a solution is currently the focus of a great fraction of the research community. Many of the methodologies designed to address this issue propose the use of endothelial cells and angiogenic growth factors, or combinations of both, to accelerate neo-vascularization after transplantation. However, an adequate solution is still elusive. In this context, we describe a methodology that combines the use of the stromal vascular fraction (SVF) isolated from adipose tissue with low oxygen culture to produce pre vascularized cell sheets as angiogenic tools for Tissue Engineering. The herein proposed approach takes advantage of the SVF angiogenic nature conferred by adipose stem cells, endothelial progenitors, endothelial and hematopoietic cells, and pericytes and further potentiates it using low oxygen, or hypoxic, culture. Freshly isolated nucleated SVF cells are cultured in hyperconfluent conditions under hypoxia (pO2 = 5 %) for up to 5 days in medium without extrinsic growth factors enabling the generation of contiguous sheets as described by the cell sheet engineering technique. Flow cytometry and immunocytochemistry allow confirming the phenotype of the different cell types composing the cell-sheets as well the organization of the CD31(+) cells in branched and highly complex tube like structures. Overall, a simple and flexible approach to promote growth factor free pre-vascularization of cell sheets for tissue engineering (TE) applications is described. PMID- 27250707 TI - Hereditary xerocytosis, a misleading anemia. PMID- 27250708 TI - Discrepancy between blood gas concentration measurements and carbon dioxide removal rate: response to comments by Du et al. PMID- 27250709 TI - Discrepancy between blood gas concentration measurements and carbon dioxide removal rate. PMID- 27250710 TI - Focus on cardiac arrest. PMID- 27250711 TI - Transgenic expression of non-structural genes of Theiler's virus suppresses initial viral replication and pathogenesis of demyelination. AB - BACKGROUND: Chronic infection with Theiler's murine encephalomyelitis virus (TMEV) in susceptible SJL/J mice induces an immune-mediated demyelinating disease and has extensively been used as a relevant infectious model for multiple sclerosis (MS). Infection of the host with many other viruses also leads to acute or chronic inflammatory diseases in the central nervous system (CNS). Levels of viral load in the host often play a critical role in the pathogenesis of virus induced diseases. Thus, the inhibition of viral replication in the host against a broad spectrum of similar viruses is critically important for preventing the viral pathogenicity. METHODS: P2/P3-expressing transgenic (B6 X SJL)F1 founders were generated and bred onto the C57BL/6 and SJL/J backgrounds. Differences in the development of demyelinating disease were compared. Viral persistence, cytokine production, and immune responses in the CNS of infected control and P2/P3-Tg mice were analyzed after infection using quantitative PCR, ELISA, and flow cytometry. Various cell types from the control and P2/P3-Tg mice, as well as cells transfected in vitro with the P2 and/or P3 regions, were also analyzed for viral replication and innate cytokine production. RESULTS: P2/P3-transgenic (P2/P3-Tg) mice carrying the viral non-structural protein genes displayed significantly reduced virus-specific T cell responses in the CNS against both the structural and non-structural proteins. Consequently, viral loads in the CNS were greater in the Tg mice during the chronic infection. However, P2/P3-Tg SJL mice exhibited reduced disease incidence and less severe clinical symptoms than did their non-transgenic littermates. Interestingly, P2/P3-Tg mice showed low viral loads in the CNS at a very early period after infection (1-3 days) with TMEV and related EMCV but not unrelated VSV. Cells from P2/P3-Tg mice and cells transfected with the P2 and/or P3 regions in vitro yielded also lower viral replication but higher IFN-alpha/beta production. CONCLUSIONS: This study demonstrates that the expression of viral non-structural genes in mice inhibits initial viral replication and suppresses sustaining pathogenic anti-viral immune responses to broad viral determinants. It appears that the elevation of innate immune cytokines produced in the cells expressing the non-structural viral genes upon viral infection is responsible for the inhibitions. The inhibition is partially virus-specific as it is more efficient for a related virus compared to an unrelated virus, suggesting a role for the similarity in the viral genome structures. Therefore, the expression of viral non-structural genes may serve as a useful new method to prevent a broadly virus-specific pathogenesis in the hosts. PMID- 27250712 TI - Erythrocyte sedimentation rate of human blood exposed to low-level laser. AB - This study is designed to investigate in vitro low-level laser (LLL) effects on rheological parameter, erythrocyte sedimentation rate (ESR), of human blood. The interaction mechanism between LLL radiation and blood is unclear. Therefore, research addresses the effects of LLL irradiation on human blood and this is essential to understanding how laser radiation interacts with biological cells and tissues. The blood samples were collected through venipuncture into EDTA containing tubes as an anticoagulant. Each sample was divided into two equal aliquots to be used as a non-irradiated sample (control) and an irradiated sample. The aliquot was subjected to doses of 36, 54, 72 and 90 J/cm(2) with wavelengths of 405, 589 and 780 nm, with a radiation source at a fixed power density of 30 mW/cm(2). The ESR and red blood cell count and volume are measured after laser irradiation and compared with the non-irradiated samples. The maximum reduction in ESR is observed with radiation dose 72 J/cm(2) delivered with a 405 nm wavelength laser beam. Moreover, no hemolysis is observed under these irradiation conditions. In a separate protocol, ESR of separated RBCs re suspended in irradiated plasma (7.6 +/- 2.3 mm/h) is found to be significantly lower (by 51 %) than their counterpart re-suspended in non-irradiated plasma (15.0 +/- 3.7 mm/h). These results indicate that ESR reduction is mainly due to the effects of LLL on the plasma composition that ultimately affect whole blood ESR. PMID- 27250713 TI - Acute effects of low-level laser therapy irradiation on blood lactate and muscle fatigue perception in hospitalized patients with heart failure-a pilot study. AB - The objective of the present study is to evaluate the acute effects of low-level laser therapy (LLLT) on functional capacity, perceived exertion, and blood lactate in hospitalized patients with heart failure (HF). Patients diagnosed with systolic HF (left ventricular ejection fraction <45 %) were randomized and allocated prospectively into two groups: placebo LLLT group (n = 10)-subjects who were submitted to placebo laser and active LLLT group (n = 10)-subjects who were submitted to active laser. The 6-min walk test (6MWT) was performed, and blood lactate was determined at rest (before LLLT application and 6MWT), immediately after the exercise test (time 0) and recovery (3, 6, and 30 min). A multi-diode LLLT cluster probe (DMC, Sao Carlos, Brazil) was used. Both groups increased 6MWT distance after active or placebo LLLT application compared to baseline values (p = 0.03 and p = 0.01, respectively); however, no difference was observed during intergroup comparison. The active LLLT group showed a significant reduction in the perceived exertion Borg (PEB) scale compared to the placebo LLLT group (p = 0.006). In addition, the group that received active LLLT showed no statistically significant difference for the blood lactate level through the times analyzed. The placebo LLLT group demonstrated a significant increase in blood lactate between the rest and recovery phase (p < 0.05). Acute effects of LLLT irradiation on skeletal musculature were not able to improve the functional capacity of hospitalized patients with HF, although it may favorably modulate blood lactate metabolism and reduce perceived muscle fatigue. PMID- 27250714 TI - Evaluation of low-level laser therapy on skeletal muscle ischemia-reperfusion in streptozotocin-induced diabetic rats by assaying biochemical markers and histological changes. AB - The purpose of the present study was to assess the effects of low-level laser therapy (LLLT) on skeletal muscle ischemia-reperfusion (IR) injuries in streptozotocin-induced diabetic rats. Twenty male Wistar rats were randomly assigned into two experimental groups, as follows: the diabetic IR group (G1, n = 10) and the diabetic IR + LLLT group (G2, n = 10). Ischemia was induced in anesthetized rats from the right femoral artery clipping for 2 h, followed by a reperfusion for 24 h. Then, the laser irradiation (K30 handheld probe, AZOR, Technica, Russia, 650 nm, 30 mW, surface area = 1 cm(2), energy density = 1.8 J/cm(2)) was carried out by irradiating the rats over a unique point on the skin over the middle region of the right gastrocnemius muscle belly three times (every 8 h), starting after initiating the reperfusion for 3 min. At the end of the reperfusion period, rats were anaesthetized and blood samples were collected and used for the estimation of pO2, pCO2, pH, HCO3, serum creatine phosphokinase (CPK), and lactate dehydrogenase (LDH). Subsequently, the right gastrocnemius muscle samples were taken for wet/dry weight ratio assessment and histological/biochemical examination. The pO2, pCO2, HCO3, and pH levels were similar for both groups (P > 0.05). The serum LDH and CPK levels were significantly lower (P < 0.05) for G2 compared to G1. In comparison to G1, tissue malondialdehyde level in G2 was significantly decreased (P < 0.05). In G2, superoxide dismutase activity was significantly increased compared to G1 (P < 0.05). Unlike G2, a significant decrease in the activity of catalase was observed in G1 (P < 0.05). The wet/dry ratio in G1 was significantly higher than that of G2 (P < 0.05). Histological examination confirmed that the extent of muscle changes in G1 was higher than G2 (P < 0.05). Finally, according to this study, LLLT has a beneficial effect on the IR muscle injury treatment in the diabetic rats. Therefore, we suggest that further research needs to be conducted using different laser parameters and examining response over a longer period of tissue recovery. PMID- 27250716 TI - Disentangling Linguistic Modality Effects in Semantic Processing. AB - Sensory systems are essential for perceiving and conceptualizing our semantic knowledge about the world and the way we interact with it. Despite studies reporting neural changes to compensate for the absence of a given sensory modality, studies focusing on the assessment of semantic processing reveal poor performances by deaf individuals when compared with hearing individuals. However, the majority of those studies were not performed in the linguistic modality considered the most adequate to their sensory capabilities (i.e., sign language). Therefore, this exploratory study was developed focusing on linguistic modality effects during semantic retrieval in deaf individuals in comparison with their hearing peers through a category fluency task. Results show a difference in performance between the two linguistic modalities by deaf individuals as well as in the type of linguistic clusters most chosen by participants, suggesting a complex clustering tendency by deaf individuals. PMID- 27250715 TI - Low level laser therapy associated with a strength training program on muscle performance in elderly women: a randomized double blind control study. AB - The aging process leads to a gradual loss of muscle mass and muscle performance, leading to a higher functional dependence. Within this context, many studies have demonstrated the benefits of a combination of physical exercise and low level laser therapy (LLLT) as an intervention that enhances muscle performance in young people and athletes. The aim of this study was to evaluate the effects of combination of LLLT and strength training on muscle performance in elderly women. For this, a hundred elderly women were screened, and 48 met all inclusion criteria to participate in this double-blind placebo-controlled trial. Volunteers were divided in three groups: control (CG = 15), strength training associated with placebo LLLT (TG = 17), and strength training associated with active LLLT (808 nm, 100 mW, 7 J) (TLG = 16). The strength training consisted of knee flexion extension performed with 80 % of 1-repetition maximum (1-RM) during 8 weeks. Several outcomes related to muscle performance were analyzed through the 6-min walk test (6-MWT), isokinetic dynamometry, surface electromyography (SEMG), lactate concentration, and 1-RM. The results revealed that a higher work (p = 0.0162), peak torque (p = 0.0309), and power (p = 0.0223) were observed in TLG compared to CG. Furthermore, both trained groups increased the 1-RM load (TG vs CG: p = 0.0067 and TLG vs CG: p < 0.0001) and decreased the lactate concentration in the third minute after isokinetic protocol (CG vs TLG: p = 0.0289 and CG vs TG: p = 0.0085). No difference in 6-MWT and in fatigue levels were observed among the groups. The present findings suggested that LLLT in combination with strength training was able to improve muscle performance in elderly people. PMID- 27250717 TI - Vitamin D supplements do not prevent falls. PMID- 27250719 TI - Managing Extended Oral Anticoagulation After Unprovoked Venous Thromboembolism. AB - Venous thromboembolism (VTE), which includes deep venous thrombosis and pulmonary embolism, is a major public health problem associated with increased morbidity and mortality. Despite the high recurrence risk associated with unprovoked VTE, extended anticoagulation remains controversial. Oral antithrombotic agents for extended VTE treatment comprise the vitamin K antagonists, aspirin, and the direct oral anticoagulants (also known as target-specific oral anticoagulants and formerly known as the new or novel oral anticoagulants) including rivaroxaban, dabigatran, apixaban, and edoxaban. The efficacy of these anticoagulants in reducing the risk of VTE recurrence (>80%-90% relative risk reduction) is offset by the risk of major bleeding that approaches 3% per year. Stratifying risks of recurrence and bleeding to identify patients at low, intermediate, or high risk and carefully considering the pharmacologic profile of the antithrombotic agents will help clinicians in choosing the optimal anticoagulant and duration and/or surveillance strategy. This review will discuss the current guidelines for extended VTE treatment, review the clinical trials involving the direct oral anticoagulants, and present the clinical considerations and concerns involving extended therapy. PMID- 27250718 TI - Characterization and differentiation of equine experimental local and early systemic inflammation by expression responses of inflammation-related genes in peripheral blood leukocytes. AB - BACKGROUND: Local inflammation may progress into systemic inflammation. To increase our understanding of the basic immunological processes during transition of equine local inflammation into a systemic state, investigation into the equine systemic immune response to local inflammation is warranted. Therefore, the aim of this study was to investigate the innate peripheral blood leukocyte (PBL) immune response to local inflammation in horses, and to compare this response with the PBL immune response during the early phase of acute systemic inflammation. Expression of 22 selected inflammation-related genes was measured in whole blood leukocytes from 6 horses in an experimental cross-over model of lipopolysaccharide- (LPS-) induced acute synovitis (3 MUg LPS intraarticularly; locally inflamed [LI] horses) and endotoxemia (1 MUg LPS/kg intravenously; systemically inflamed [SI] horses). Multiple clinical and hematological/biochemical examinations were performed, and serial blood samples were analyzed by reverse transcription quantitative real-time PCR. Post-induction expression profiles of all genes were compared between study groups using principal component analysis (PCA) and hierarchical clustering. RESULTS: Moderate synovitis and mild systemic inflammation of approximately 24 h duration was confirmed by clinical and paraclinical observations in LI and SI horses, respectively. In the LI group, samples obtained 3-16 h post-injection showed distinct clustering in the PCA compared with baseline levels, indicating a transcriptional response to local inflammation in PBLs in this time interval. There was no clinical or hematological indication of actual systemic inflammation. There was a clear separation of all LI samples from all SI samples in two distinct clusters, indicating that expression profiles in the two study groups were different, independent of time since LPS injection. Co-regulated genes formed four clusters across study groups which were distinctly differently regulated. Only few of individual genes displayed different expression between the study groups at all times after LPS injection. CONCLUSIONS: Local inflammation in horses initiated an innate transcriptional response in PBLs, which differed from the transcriptional response during the early phase of systemic inflammation. This study may provide new insights into the immunobiology of PBLs during the transition of local inflammation into a systemic state. PMID- 27250721 TI - Erratum to: Hidden musculoskeletal involvement in inflammatory bowel disease: a multicenter ultrasound study. PMID- 27250720 TI - Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression. AB - Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ERalpha and ERbeta were involved in the protection by tibolone on GD cells, being ERbeta preferentially involved on these actions over ERalpha. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERbeta antagonist and partially blocked by an ERalpha antagonist. Furthermore, ERbeta inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondrial membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ERbeta and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERbeta and the upregulation of neuroglobin. PMID- 27250722 TI - Safety and Outcomes of Capsule Endoscopy in Patients with Left Ventricular Assist Device: a Single-Center Retrospective Case Series. AB - Obscure gastrointestinal bleeding (GIB) in patients with continuous-flow left ventricular assist devices (CF-LVAD) is common. Capsule endoscopy (CE) can be used in the diagnosis of obscure GIB. Safety and outcomes of CE in patients with CF-LVAD are unknown. The aim is to define the safety and outcomes of CE in this population. Paitents with CF-LVAD undergoing CE at a single center between 2007 and 2014 were retrospectively reviewed. Thirty-four CE studies were performed. Positive CE occurred in 19 studies. No clinically significant cardiac events occurred. Medical intervention was the most common management strategy. Rebleeding after CE occurred in 10 patients. Patients with active bleeding or lesions such as arteriovenous malformations (AVM) incurred a higher risk of rebleeding, transfusion, and repeated endoscopy. CE is safe in patients with CF LVAD. The risk of rebleeding was more common in patients with active bleeding or AVM lesions although this result did not reach statistical significance. PMID- 27250724 TI - [Not Available]. PMID- 27250723 TI - A Multidisciplinary Assessment of Remote Myocardial Fibrosis After Reperfused Myocardial Infarction in Swine and Patients. AB - In extensive nonreperfused myocardial infarction (MI), remote fibrosis has been documented. Early reperfusion by primary angioplasty represents the gold standard method to minimize the extension of the infarction. We aimed to ascertain whether fibrosis also affects remote regions in reperfused MI in swine and patients. Swine were subjected to a transient occlusion of the left anterior descending artery followed by 1-week or 1-month reperfusion. Collagen content in the remote area macroscopically, microscopically, by magnetic resonance microimaging, and at the molecular level was similar to controls. In patients with previous MI, samples from autopsies displayed a significant increase in collagen content only in the infarct region. In patients with previous MI submitted to cardiac magnetic resonance-T1 mapping, the extracellular volume fraction in remote segments was similar to that for controls. In all scenarios, the remote region did not show a significant increase of collagen content in comparison with controls. PMID- 27250725 TI - Implantable cardioverter-defibrillators in congenital heart disease. AB - Implantable cardioverter-defibrillators (ICD) have an important role in reducing sudden cardiac death in patients with congenital heart disease (CHD); however, the benefit of ICDs needs to be weighed up against both short-term and long-term adverse effects, which are difficult to evaluate in the heterogeneous CHD population. A tailored approach, taking into account risk stratification and patient-specific factors, is needed to select the most appropriate strategy. This review discusses primary and secondary ICD indications, implantation approaches and long-term follow-up. Recent publications have shed light on the concerns of system longevity, lead extractions, inappropriate shocks and impact on the quality of life. All of these factors require consideration prior to commitment to this long-term treatment strategy. PMID- 27250726 TI - [Arrhythmia in adults with congenital heart defects : Atrial tachycardia]. AB - Atrial arrhythmias are frequently encountered in patients with congenital heart disease (CHD) with or without corrective surgery and respond to pharmacological therapies with only limited success. This review describes the technologies currently available for performing successful ablation procedures in this very complex patient cohort. In addition to an understanding of the underlying anatomy, which can be supplemented by 3D imaging with the aid of magnetic resonance imaging (MRI) or computed tomography (CT), the choice between the different 3D mapping systems (sequential versus simultaneous) is presented. Finally, conventional manual navigation is compared with magnetic navigation and then discussed with regard to the respective arrhythmias encountered with the different forms of CHD. PMID- 27250727 TI - Ligation-Assisted Endoscopic Enucleation for the Resection of Gastrointestinal Tumors Originating from the Muscularis Propria: Analysis of Efficacy and Facility. AB - BACKGROUND: Gastrointestinal tumors originating from the muscularis propria are believed to have the potential to progress to malignant tumors. The efficacy of 'pre-management' with elastic band or endoloop assistant ligation after initial submucosal dissection in endoscopic enucleation procedure of these tumors was investigated and evaluated. METHODS: The study included 21 patients with small gastric stromal tumors arising in the gastric muscularis propria as determined by endoscopy (endoscopic ultrasonography). A standard endoscope with a transparent cap attached to the tip was used. The cap was placed over the lesion, after incision of the surrounding tissue, maximum sustained suction was applied. Then the elastic band or endoloop was released around the base. Circumference resection was performed with clips strengthening the defect closure. RESULTS: The 22 gastrointestinal stromal tumors sloughed completely. The mean time required for the full-thickness resection was 48 min. Minor perforation occurred with metal clips closing the defect of the gastric wall. Follow-up ranged from 13 to 42 months, during which time no recurrence was observed postoperatively. CONCLUSIONS: The band or endoloop assistant endoscopic ligation technique is effective for the enucleation of deep gastric tumors. It may help avoiding disturbance the abdominal cavity hemostasis in traditional full-thickness enucleation procedure. PMID- 27250728 TI - The value of CT and MRI in the classification and surgical decision-making among spine surgeons in thoracolumbar spinal injuries. AB - PURPOSE: Although imaging has a major role in evaluation and management of thoracolumbar spinal trauma by spine surgeons, the exact role of computed tomography (CT) and magnetic resonance imaging (MRI) in addition to radiographs for fracture classification and surgical decision-making is unclear. METHODS: Spine surgeons (n = 41) from around the world classified 30 thoracolumbar fractures. The cases were presented in a three-step approach: first plain radiographs, followed by CT and MRI images. Surgeons were asked to classify according to the AOSpine classification system and choose management in each of the three steps. RESULTS: Surgeons correctly classified 43.4 % of fractures with plain radiographs alone; after, additionally, evaluating CT and MRI images, this percentage increased by further 18.2 and 2.2 %, respectively. AO type A fractures were identified in 51.7 % of fractures with radiographs, while the number of type B fractures increased after CT and MRI. The number of type C fractures diagnosed was constant across the three steps. Agreement between radiographs and CT was fair for A-type (k = 0.31), poor for B-type (k = 0.19), but it was excellent between CT and MRI (k > 0.87). CT and MRI had similar sensitivity in identifying fracture subtypes except that MRI had a higher sensitivity (56.5 %) for B2 fractures (p < 0.001). The need for surgical fixation was deemed present in 72 % based on radiographs alone and increased to 81.7 % with CT images (p < 0.0001). The assessment for need of surgery did not change after an MRI (p = 0.77). CONCLUSION: For accurate classification, radiographs alone were insufficient except for C-type injuries. CT is mandatory for accurately classifying thoracolumbar fractures. Though MRI did confer a modest gain in sensitivity in B2 injuries, the study does not support the need for routine MRI in patients for classification, assessing instability or need for surgery. PMID- 27250729 TI - Development and psychometric evaluation of a health questionnaire on back care knowledge in daily life physical activities for adolescent students. AB - PURPOSE: The most relevant musculoskeletal problems are related with back health. Study instruments have been designed for adult patient population but not for school-aged children. The aim of this study was to develop and evaluate the psychometric properties of a questionnaire to assess adolescents' level of back care knowledge in daily life physical activities. METHODS: Participants were 171 adolescents from secondary schools. The questionnaire was made up of 24 questions. A Delphi method was used for test validation. Cronbach's alpha, test retest, Wilcoxon signed-rank and Bland-Altman graph were used to evaluate the instrument reliability. RESULTS: Cronbach's alpha (alpha = 0.82) showed a strong internal consistency. Test-retest was excellent for total score (0.76) and moderate to excellent (0.54-0.76) for seven score conceptual categories with good results of standard error of the mean and minimal detectable change. No differences were found between test 1 and test 2 except for the standing posture scores. CONCLUSION: The questionnaire showed acceptable psychometric values. Results showed that this questionnaire is a good instrument to assess adolescent's back care knowledge. PMID- 27250730 TI - BReastfeeding Attitude and Volume Optimization (BRAVO) trial: study protocol for a randomized controlled trial. AB - BACKGROUND: A growing body of evidence shows the short-term benefits of breastfeeding, which include protection against infections, allergies, and lung diseases. However, evidence on the long-term benefits of breastfeeding is scarce and often conflicting. The BReastfeeding Attitude and Volume Optimization (BRAVO) trial is designed to study the effect of breastfeeding on early signs of later chronic diseases, particularly cardiovascular, respiratory, and metabolic risks later in life. In addition, the effectiveness of breastfeeding empowerment in promoting breastfeeding will also be evaluated. METHODS/DESIGN: This study is an ongoing randomized trial in Jakarta, Indonesia, that began in July 2012. Pregnant women are being screened for their breastfeeding plan in the third trimester, and those with low intention to breastfeed are randomly allocated to either receiving an add-on breastfeeding-optimization program or usual care. Primary outcomes include breastfeeding rate, lung function, and blood pressure during the first year of life and vascular/cardiac characteristics, which will be measured at the age of 4 to 5 years. Child growth and infection/illness episodes are measured, whereas cognitive testing is planned for the children at 5 years of age. DISCUSSION: To date, 784 women (80 %) have been randomized of the 1,000 planned, with satisfactory completeness of the 1-year follow up (90.1 %). Included mothers are of lower socioeconomic status and more often have blue-collar jobs, similar to what was observed in the pilot study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01566812 . Registered on 27 March 2012. PMID- 27250731 TI - Emotional Control Mediates the Association Between Dimensions of Perfectionism and Worry in Children. AB - Previous research has shown that perfectionism predicts for increased worry in children. Theoretically, children with high levels of perfectionism may show a decreased ability to control their emotions during times of perceived failure. Children may then worry as a maladaptive attempt to cope with intense emotions. The current study sought to test the mediating role of emotional control on the relation between perfectionism dimensions and worry in children. Participants were 66 parent-child dyads. Children were 7-13 years (50 % male; 77.3 % Caucasian, 9.1 % African American). Overall the model fit the data well. Results indicated that perfectionism domains predicted for emotional control deficits and increased worry. Emotional control also partially mediated the relation between perfectionism dimensions and worry. These results suggest that emotional control may be one mechanism through which perfectionism exerts its effect on worry and perfectionistic children may worry due to difficulty controlling their emotional responses. PMID- 27250732 TI - Multifunctional Nitrogen-Doped Loofah Sponge Carbon Blocking Layer for High Performance Rechargeable Lithium Batteries. AB - Low-cost, long-life, and high-performance lithium batteries not only provide an economically viable power source to electric vehicles and smart electricity grids but also address the issues of the energy shortage and environmental sustainability. Herein, low-cost, hierarchically porous, and nitrogen-doped loofah sponge carbon (N-LSC) derived from the loofah sponge has been synthesized via a simple calcining process and then applied as a multifunctional blocking layer for Li-S, Li-Se, and Li-I2 batteries. As a result of the ultrahigh specific area (2551.06 m(2) g(-1)), high porosity (1.75 cm(3) g(-1)), high conductivity (1170 S m(-1)), and heteroatoms doping of N-LSC, the resultant Li-S, Li-Se, and Li-I2 batteries with the N-LSC-900 membrane deliver outstanding electrochemical performance stability in all cases, i.e., high reversible capacities of 623.6 mA h g(-1) at 1675 mA g(-1) after 500 cycles, 350 mA h g(-1) at 1356 mA g(-1) after 1000 cycles, and 150 mA h g(-1) at 10550 mA g(-1) after 5000 cycles, respectively. The successful application to Li-S, Li-Se, and Li-I2 batteries suggests that loofa sponge carbon could play a vital role in modern rechargeable battery industries as a universal, cost-effective, environmentally friendly, and high-performance blocking layer. PMID- 27250733 TI - The impact of irradiance on optimal and cellular nitrogen to phosphorus ratios in phytoplankton. AB - Phytoplankton acclimates to irradiance by regulating the cellular content of light-harvesting complexes, which are nitrogen (N) rich and phosphorus (P) poor. Irradiance is thus hypothesised to influence the cellular N : P ratio and the N : P defining the threshold between N and P limitation (the 'optimal' N : P). We tested this hypothesis by first addressing the response of the optimal N : P to irradiance in a controlled experiment with Chlamydomonas reinhardtii. Then, we did a meta-analysis of experimental data on optimal and cellular N : P ratios across light gradients to test the generality of an N : P to light response within species. In both the experiment and the meta-analysis, N : P ratios decreased with irradiance, indicating that factors affecting underwater irradiance, like depth and the composition of the water, may influence the relative N : P requirement. The effect of irradiance did not differ between optimal and cellular N : P ratios, but observations of optimal N : P were on average 2.8 times higher than observations of cellular N : P. PMID- 27250734 TI - The Influence of a Mexican Cultural Immersion Experience on Personal and Professional Healthcare Practices. AB - The purpose of this study was to understand the influence of a cultural immersion experience on personal and professional healthcare practices of occupational therapists. The experience, a 10-day course in Oaxaca, Mexico, exposed participants to alternative and complementary medicine through interactive sessions with Mexican indigenous traditional healers. The literature indicates that cultural immersion experiences can increase the perceived cultural effectiveness of healthcare professionals. Three focus groups were conducted with eight occupational therapists and two occupational therapy fieldwork students who had participated in the course. Themes were coded based on responses to each question by two graduate students and a qualitative researcher. Four major themes emerged regarding the influence of a cultural immersion experience on personal and professional healthcare practices of occupational therapists: (1) Natural Remedies; (2) Mind, Body, Spirit Connection; (3) Increased Openness; and (4) Challenges of Integrating Traditional and Western Medicine. The themes derived from this study confirmed the advantages of a cultural immersion experience on both the personal and professional views and practices of occupational therapists. Cultural immersion courses can assist occupational therapists to better understand different cultural views of health, disability and healing in order to provide quality occupational therapy care in a multicultural society. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27250736 TI - Occurrences, sources and risk assessment of short- and medium-chain chlorinated paraffins in sediments from the middle reaches of the Yellow River, China. AB - Chlorinated paraffins (CPs), one class of hydrophobic and toxic compounds, are easily adsorbed into sediments and then pose potential risks to the ecosystem and human health. However, few researches on short- and medium-chain CPs (SCCPs and MCCPs) in sediments have been performed. In order to comprehensively investigate the spatial distributions, sources, and ecological risks of CPs, sediments collected from the middle reaches of the Yellow River were analyzed by two dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC * GC-TOFMS). The concentrations of SCCPs and MCCPs ranged from 11.6 to 9.76 * 103 ng/g dry weight (dw) and from 8.33 to 168 ng/g dw, respectively. No significant correlation was found between total organic carbon (TOC) and CP concentrations (P > 0.05). The spatial distributions showed that contamination levels of CPs were relevant to human activities. In addition, two types of sediment samples were classified by hierarchical cluster analysis (HCA) and results indicated the predominant congener groups were C10Cl6-7 for SCCPs and C14Cl7-8 for MCCPs. Principal component analysis (PCA) revealed that SCCPs and MCCPs in the sediments may have different sources, and SCCPs are likely to come from the production and use of CP-42 and CP-52. Moreover, complex environmental processes, including long range transportation via the atmosphere and/or river, deposition and degradation of CPs, resulted in increased abundances of short chain and low chlorinated congeners in sediment samples compared with commercial mixtures, and different homolog patterns among samples. The significant negative correlation between SCCP concentrations and MCCP/SCCP ratios could be related to long-range transport of CPs. A preliminary risk assessment indicated that CPs at current levels posed no significant ecological risk. PMID- 27250735 TI - miR-146a is essential for lipopolysaccharide (LPS)-induced cross-tolerance against kidney ischemia/reperfusion injury in mice. AB - MicroRNA-146a is one of most important microRNAs involved in development of endotoxin tolerance via (toll-like receptors) TLRs/ NF-kappaB pathway. In this study, we sought to identify the mechanistic role of miR-146a in mediating the protective effect of lipopolysaccharide (LPS) pretreatment on kidney ischemia/reperfusion injury. A locked nucleic acid-modified anti-miR-146a given before LPS treatment knocked down miR-146a expression and completely negated LPS mediated protection against kidney ischemia/reperfusion injury. Knockdown of miR 146a resulted in significantly higher histopathological scores for tubular damage, expression of proinflammatory cytokines and chemokines, and neutrophil and macrophage infiltration. Furthermore, knockdown of miR-146a greatly up regulated the protein levels of IL-1 receptor-associated kinase (IRAK-1) and tumor-necrosis factor (TNF) receptor-associated factor 6 (TRAF6), which are known target genes of miR-146a, leading to activation of NF-kappaB. Finally, elevation of nuclear translocation of NF-kappaB p65/p50 and caspase-3 expression, degradation of cytosolic IkBalpha and BcL-xL, and substantially exacerbation of tubular cell apoptosis were inversely correlated with miR-146a expression. Taken together, our results identify that miR146a exerts a kidney protective effect through negative regulation of acute inflammatory response by suppressing NF kappaB activation and proinflammatory genes expression. PMID- 27250737 TI - Nutrition and bone health. AB - Low bone mass leads to fracture risk. Osteoporosis affects over 10% of the population and one of every two women over the age of 50 years. Genetics predicts more than half of bone mass. Diet and weight bearing exercise are two lifestyle choices that can influence the risk of fracture. Nutrients are the structural constituents of bone. As bone is a living tissue and turns over, albeit more slowly than other tissues, there is an obligatory loss of minerals daily that must be replaced through diet. Three servings of dairy products daily are recommended to replace those losses. Alternative sources of nutrients can come from calcium fortified orange juice, plant-based beverages, or tofu to provide many nutrients needed for bone health. Supplements can provide nutrients at risk for being inadequate such as calcium or vitamin D. PMID- 27250738 TI - Prevalence of prenatal depression and associated factors among HIV-positive women in primary care in Mpumalanga province, South Africa. AB - This study aimed to assess the prevalence of depressed symptoms and associated factors in prenatal HIV-positive women in primary care facilities in rural South Africa. In a cross-sectional study, 663 HIV-positive prenatal women in 12 community health centres in Mpumalanga province, South Africa, were recruited by systematic sampling (every consecutive patient after HIV post-test counselling). Results indicate that overall, 48.7% [95% CI: 44.8, 52.6] of women during the prenatal period reported depressed mood (scores of >= 13 on the Edinburgh Postnatal Depression Scale 10). In multivariate analysis, not being employed, unplanned pregnancy, not having an HIV-positive child, poor antiretroviral therapy adherence, non-condom use at last sex, and intimate partner violence were associated with depressive symptoms. Potential risk factors among HIV-infected prenatal women were identified which could be utilized in interventions. Routine screening for depression may be integrated into prenatal care settings. PMID- 27250739 TI - Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study. AB - BACKGROUND: The cost and complexity of current approaches to therapeutic drug monitoring during tuberculosis (TB) therapy limits widespread use in areas of greatest need. We sought to determine whether urine colorimetry could have a novel application as a form of therapeutic drug monitoring during anti-TB therapy. METHODS: Among healthy volunteers, we evaluated 3 dose sizes of rifampin (150 mg, 300 mg, and 600 mg), performed intensive pharmacokinetic sampling, and collected a timed urine void at 4 h post-dosing. The absorbance peak at 475 nm was measured after rifamycin extraction. The optimal cutoff was evaluated in a study of 39 HIV/TB patients undergoing TB treatment in Botswana. RESULTS: In the derivation study, a urine colorimetric assay value of 4.0 * 10(-2) Abs, using a timed void 4 h after dosing, demonstrated a sensitivity of 92 % and specificity of 60 % to detect a peak rifampin concentration (Cmax) under 8 mg/L, with an area under the ROC curve of 0.92. In the validation study, this cutoff was specific (100 %) but insensitive (28 %). We observed similar test characteristics for a target Cmax target of 6.6 mg/L, and a target area under the drug concentration versus-time curve (AUC0-8) target of 24.1 mg*hour/L. CONCLUSIONS: The urine colorimetric assay was specific but insensitive to detect low rifampin serum concentrations among HIV/TB patients. In future work we will attempt to optimize sampling times and assay performance, with the goal of delivering a method that can translate into a point-of-care assessment of rifampin exposure during anti-TB therapy. PMID- 27250740 TI - Electrostatic Control of Isoform Selective Inhibitor Binding in Nitric Oxide Synthase. AB - Development of potent and isoform selective nitric oxide synthase (NOS) inhibitors is challenging because of the structural similarity in the heme active sites. One amino acid difference between NOS isoforms, Asp597 in rat neuronal NOS (nNOS) versus Asn368 in bovine endothelial NOS (eNOS), has been identified as the structural basis for why some dipeptide amide inhibitors bind more tightly to nNOS than to eNOS. We now have found that the same amino acid variation is responsible for substantially different binding modes and affinity for a new class of aminopyridine-based inhibitors. PMID- 27250741 TI - Adrenalectomy: postoperative survival data. PMID- 27250742 TI - Effects of positive end-expiratory pressure and 30% inspired oxygen on pulmonary mechanics and atelectasis in cats undergoing non-bronchoscopic bronchoalveolar lavage. AB - Objectives The objective of this study was to determine if modification of inspired oxygen concentration or positive end-expiratory pressure (PEEP) would alter bronchoalveolar lavage (BAL)-induced changes in pulmonary mechanics or atelectasis, as measured using ventilator-acquired pulmonary mechanics and thoracic CT. Methods Six experimentally asthmatic cats underwent anesthesia and non-bronchoscopic BAL, each under four randomized treatment conditions: 100% oxygen, zero PEEP; 30% oxygen, zero PEEP; 100% oxygen, PEEP 2 cmH2O; and 30% oxygen, PEEP 2 cmH2O. Pulse oximetry was used to estimate oxygen saturation (SpO2). Ventilator-acquired pulmonary mechanics and thoracic CT scans were collected prior to BAL and at 1, 5 and 15 mins post-BAL. Results While receiving 100% oxygen, no cat had SpO2 <91%. Some cats receiving 30% oxygen had decreased saturation immediately post-BAL (mean +/- SD 70.8 +/- 31%), but 6/8 of these had SpO2 >90% by 1 min later. There was a significant increase in airway resistance and a decrease in lung compliance following BAL, but there was no significant difference between treatment groups. Cats receiving no PEEP and 30% oxygen conserved better aeration of the lung parenchyma in BAL-sampled areas than those receiving no PEEP and 100% oxygen. Conclusions and relevance Alterations in pulmonary mechanics or atelectasis may not be reflected by SpO2 following BAL. The use of 30% inspired oxygen concentration failed to show any significant improvement in pulmonary mechanics but did diminish atelectasis. In some cats, it was also associated with desaturation of hemoglobin. The use of PEEP in this study did not show any effect on our outcome parameters. Further studies using higher PEEP (5-10 cmH2O) and intermediate inspired oxygen concentration (40-60%) are warranted to determine if they would confer clinical benefit in cats undergoing diagnostic BAL. PMID- 27250743 TI - Synergetic electrode architecture for efficient graphene-based flexible organic light-emitting diodes. AB - Graphene-based organic light-emitting diodes (OLEDs) have recently emerged as a key element essential in next-generation displays and lighting, mainly due to their promise for highly flexible light sources. However, their efficiency has been, at best, similar to that of conventional, indium tin oxide-based counterparts. We here propose an ideal electrode structure based on a synergetic interplay of high-index TiO2 layers and low-index hole-injection layers sandwiching graphene electrodes, which results in an ideal situation where enhancement by cavity resonance is maximized yet loss to surface plasmon polariton is mitigated. The proposed approach leads to OLEDs exhibiting ultrahigh external quantum efficiency of 40.8 and 62.1% (64.7 and 103% with a half-ball lens) for single- and multi-junction devices, respectively. The OLEDs made on plastics with those electrodes are repeatedly bendable at a radius of 2.3 mm, partly due to the TiO2 layers withstanding flexural strain up to 4% via crack deflection toughening. PMID- 27250745 TI - Phosphoketolase pathway contributes to carbon metabolism in cyanobacteria. AB - Central carbon metabolism in cyanobacteria comprises the Calvin-Benson-Bassham (CBB) cycle, glycolysis, the pentose phosphate (PP) pathway and the tricarboxylic acid (TCA) cycle. Redundancy in this complex metabolic network renders the rational engineering of cyanobacterial metabolism for the generation of biomass, biofuels and chemicals a challenge. Here we report the presence of a functional phosphoketolase pathway, which splits xylulose-5-phosphate (or fructose-6 phosphate) to acetate precursor acetyl phosphate, in an engineered strain of the model cyanobacterium Synechocystis (DeltaglgC/xylAB), in which glycogen synthesis is blocked, and xylose catabolism enabled through the introduction of xylose isomerase and xylulokinase. We show that this mutant strain is able to metabolise xylose to acetate on nitrogen starvation. To see whether acetate production in the mutant is linked to the activity of phosphoketolase, we disrupted a putative phosphoketolase gene (slr0453) in the DeltaglgC/xylAB strain, and monitored metabolic flux using (13)C labelling; acetate and 2-oxoglutarate production was reduced in the light. A metabolic flux analysis, based on isotopic data, suggests that the phosphoketolase pathway metabolises over 30% of the carbon consumed by DeltaglgC/xylAB during photomixotrophic growth on xylose and CO2. Disruption of the putative phosphoketolase gene in wild-type Synechocystis also led to a deficiency in acetate production in the dark, indicative of a contribution of the phosphoketolase pathway to heterotrophic metabolism. We suggest that the phosphoketolase pathway, previously uncharacterized in photosynthetic organisms, confers flexibility in energy and carbon metabolism in cyanobacteria, and could be exploited to increase the efficiency of cyanobacterial carbon metabolism and photosynthetic productivity. PMID- 27250746 TI - Flexibility in the structure of spiral flowers and its underlying mechanisms. AB - Spiral flowers usually bear a variable number of organs, suggestive of the flexibility in structure. The mechanisms underlying the flexibility, however, remain unclear. Here we show that in Nigella damascena, a species with spiral flowers, different types of floral organs show different ranges of variation in number. We also show that the total number of organs per flower is largely dependent on the initial size of the floral meristem, whereas the respective numbers of different types of floral organs are determined by the functional domains of corresponding genetic programmes. By conducting extensive expression and functional studies, we further elucidate the genetic programmes that specify the identities of different types of floral organs. Notably, the AGL6-lineage member NdAGL6, rather than the AP1-lineage members NdFL1/2, is an A-function gene, whereas petaloidy of sepals is not controlled by AP3- or PI-lineage members. Moreover, owing to the formation of a regulatory network, some floral organ identity genes also regulate the boundaries between different types of floral organs. On the basis of these results, we propose that the floral organ identity determination programme is highly dynamic and shows considerable flexibility. Transitions from spiral to whorled flowers, therefore, may be explained by evolution of the mechanisms that reduce the flexibility. PMID- 27250744 TI - Comparison of Two ELISA Methods and Mass Spectrometry for Measurement of Vitamin D-Binding Protein: Implications for the Assessment of Bioavailable Vitamin D Concentrations Across Genotypes. AB - Studies using vitamin D-binding protein (DBP) concentrations to estimate free and bioavailable vitamin D have increased dramatically in recent years. Combinations of two single-nucleotide polymorphisms (SNPs) produce three major DBP isoforms (Gc1f, Gc1s, and Gc2). A recent study showed that DBP concentrations quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) did not differ by race, whereas a widely used monoclonal enzyme-linked immunosorbent assay (ELISA) quantified DBP differentially by isoform, yielding significantly lower DBP concentrations in black versus white individuals. We compared measurements of serum DBP using a monoclonal ELISA, a polyclonal ELISA, and LC-MS/MS in 125 participants in the Chronic Renal Insufficiency Cohort (CRIC). Serum free and bioavailable 25OHD were calculated based on DBP concentrations from these three assays in homozygous participants, and race differences were compared. We confirmed that the monoclonal ELISA quantifies DBP differentially by isoform and showed that the polyclonal ELISA is not subject to this bias. Whereas <=9% of the variability in DBP concentrations quantified using either LC-MS/MS or the polyclonal ELISA was explained by genotype, 85% of the variability in the monoclonal ELISA-based measures was explained by genotype. DBP concentrations measured by the monoclonal ELISA were disproportionately lower than LC-MS/MS based results for Gc1f homozygotes (median difference -67%; interquartile range [IQR] -71%, -64%), 95% of whom were black. In contrast, the polyclonal ELISA yielded consistently and similarly higher measurements of DBP than LC-MS/MS, irrespective of genotype, with a median percent difference of +50% (IQR +33%, +65%). Contrary to findings using the monoclonal ELISA, DBP concentrations did not differ by race, and free and bioavailable 25OHD were significantly lower in black versus white participants based on both the polyclonal ELISA and LC-MS/MS, consistent with their lower total 25OHD. Future studies of DBP and free or bioavailable vitamin D metabolites should employ DBP assays that are not biased by DBP genotype. (c) 2016 American Society for Bone and Mineral Research. PMID- 27250747 TI - Control of grain size and rice yield by GL2-mediated brassinosteroid responses. AB - Given the continuously growing population and decreasing arable land, food shortage is becoming one of the most serious global problems in this century(1). Grain size is one of the determining factors for grain yield and thus is a prime target for genetic breeding(2,3). Although a number of quantitative trait loci (QTLs) associated with rice grain size have been identified in the past decade, mechanisms underlying their functions remain largely unknown(4,5). Here we show that a grain-length-associated QTL, GL2, has the potential to improve grain weight and grain yield up to 27.1% and 16.6%, respectively. We also show that GL2 is allelic to OsGRF4 and that it contains mutations in the miR396 targeting sequence. Because of the mutation, GL2 has a moderately increased expression level, which consequently activates brassinosteroid responses by upregulating a large number of brassinosteroid-induced genes to promote grain development. Furthermore, we found that GSK2, the central negative regulator of rice brassinosteroid signalling, directly interacts with OsGRF4 and inhibits its transcription activation activity to mediate the specific regulation of grain length by the hormone. Thus, this work demonstrates the feasibility of modulating specific brassinosteroid responses to improve plant productivity. PMID- 27250748 TI - Blocking miR396 increases rice yield by shaping inflorescence architecture. AB - Strategies to increase rice productivity to meet the global demand have been the main concern of breeders around the world. Although a growing number of functional genes related to crop yield have been characterized, our understanding of its associated regulatory pathways is limited. Using rice as a model, we find that blocking miR396 greatly increases grain yield by modulating development of auxiliary branches and spikelets through direct induction of the growth regulating factor 6 (OsGRF6) gene. The upregulation of OsGRF6 results in the coordinated activation of several immediate downstream biological clades, including auxin (IAA) biosynthesis, auxin response factors, and branch and spikelet development-related transcription factors. This study describes a conserved microRNA (miRNA)-dependent regulatory module that integrates inflorescence development, auxin biosynthesis and signalling pathways, and could potentially be used in engineering high-yield crop plants. PMID- 27250749 TI - Regulation of OsGRF4 by OsmiR396 controls grain size and yield in rice. AB - An increase in grain yield is crucial for modern agriculture(1). Grain size is one of the key components of grain yield in rice and is regulated by quantitative trait loci (QTLs)(2,3). Exploring new QTLs for grain size will help breeders develop elite rice varieties with higher yields(3,4). Here, we report a new semi dominant QTL for grain size and weight (GS2) in rice, which encodes the transcription factor OsGRF4 (GROWTH-REGULATING FACTOR 4) and is regulated by OsmiR396. We demonstrate that a 2 bp substitution mutation in GS2 perturbs OsmiR396-directed regulation of GS2, resulting in large and heavy grains and increased grain yield. Further results reveal that GS2 interacts with the transcription coactivitors OsGIF1/2/3, and overexpression of OsGIF1 increases grain size and weight. Thus, our findings define the regulatory mechanism of GS2, OsGIFs and OsmiR396 in grain size and weight control, suggesting this pathway could be used to increase yields in crops. PMID- 27250751 TI - Yield increase: GRFs provide the key. PMID- 27250750 TI - Rice domestication occurred through single origin and multiple introgressions. PMID- 27250754 TI - Floral flexibility: Diversification of the flower. PMID- 27250752 TI - Molecular and genetic control of plant thermomorphogenesis. AB - Temperature is a major factor governing the distribution and seasonal behaviour of plants. Being sessile, plants are highly responsive to small differences in temperature and adjust their growth and development accordingly. The suite of morphological and architectural changes induced by high ambient temperatures, below the heat-stress range, is collectively called thermomorphogenesis. Understanding the molecular genetic circuitries underlying thermomorphogenesis is particularly relevant in the context of climate change, as this knowledge will be key to rational breeding for thermo-tolerant crop varieties. Until recently, the fundamental mechanisms of temperature perception and signalling remained unknown. Our understanding of temperature signalling is now progressing, mainly by exploiting the model plant Arabidopsis thaliana. The transcription factor PHYTOCHROME INTERACTING FACTOR 4 (PIF4) has emerged as a critical player in regulating phytohormone levels and their activity. To control thermomorphogenesis, multiple regulatory circuits are in place to modulate PIF4 levels, activity and downstream mechanisms. Thermomorphogenesis is integrally governed by various light signalling pathways, the circadian clock, epigenetic mechanisms and chromatin-level regulation. In this Review, we summarize recent progress in the field and discuss how the emerging knowledge in Arabidopsis may be transferred to relevant crop systems. PMID- 27250753 TI - Mechanisms and evolution of plant resistance to aphids. AB - Aphids are important herbivores of both wild and cultivated plants. Plants rely on unique mechanisms of recognition, signalling and defence to cope with the specialized mode of phloem feeding by aphids. Aspects of the molecular mechanisms underlying aphid-plant interactions are beginning to be understood. Recent advances include the identification of aphid salivary proteins involved in host plant manipulation, and plant receptors involved in aphid recognition. However, a complete picture of aphid-plant interactions requires consideration of the ecological outcome of these mechanisms in nature, and the evolutionary processes that shaped them. Here we identify general patterns of resistance, with a special focus on recognition, phytohormonal signalling, secondary metabolites and induction of plant resistance. We discuss how host specialization can enable aphids to co-opt both the phytohormonal responses and defensive compounds of plants for their own benefit at a local scale. In response, systemically induced resistance in plants is common and often involves targeted responses to specific aphid species or even genotypes. As co-evolutionary adaptation between plants and aphids is ongoing, the stealthy nature of aphid feeding makes both the mechanisms and outcomes of these interactions highly distinct from those of other herbivore plant interactions. PMID- 27250755 TI - Crop genetics: Oil prospecting. PMID- 27250757 TI - Signalling: Poisoning the well. PMID- 27250756 TI - Tomato domestication: Slowing down the clock. PMID- 27250758 TI - Photorespiration: In the balance. PMID- 27250759 TI - Happy birthday to us. PMID- 27250760 TI - Molecular mechanism and functional significance of acid generation in the Drosophila midgut. AB - The gut of Drosophila melanogaster includes a proximal acidic region (~pH 2), however the genome lacks the H(+)/K(+) ATPase characteristic of the mammalian gastric parietal cell, and the molecular mechanisms of acid generation are poorly understood. Here, we show that maintenance of the low pH of the acidic region is dependent on H(+) V-ATPase, together with carbonic anhydrase and five further transporters or channels that mediate K(+), Cl(-) and HCO3(-) transport. Abrogation of the low pH did not influence larval survival under standard laboratory conditions, but was deleterious for insects subjected to high Na(+) or K(+) load. Insects with elevated pH in the acidic region displayed increased susceptibility to Pseudomonas pathogens and increased abundance of key members of the gut microbiota (Acetobacter and Lactobacillus), suggesting that the acidic region has bacteriostatic or bacteriocidal activity. Conversely, the pH of the acidic region was significantly reduced in germ-free Drosophila, indicative of a role of the gut bacteria in shaping the pH conditions of the gut. These results demonstrate that the acidic gut region protects the insect and gut microbiome from pathological disruption, and shed light on the mechanisms by which low pH can be maintained in the absence of H(+), K(+) ATPase. PMID- 27250761 TI - Normal Newborn Heart Rate in the First Five Minutes of Life Assessed by Dry Electrode Electrocardiography. AB - BACKGROUND: There is limited evidence regarding the heart rate (HR) during the first minutes of life. Nonetheless, resuscitative actions within the first minute are partly guided by different HR levels. The advent of an electrocardiographic (ECG) HR sensor with early HR detection has provided the opportunity to study changes immediately following delivery. OBJECTIVE: The objectives were to determine immediately following delivery: (i) the time to achievement of reliable ECG signals using dry electrodes, (ii) changes in HR, and (iii) the influence of the onset of breathing and cord clamping on the HR. METHODS: Healthy term neonates were randomly included between July and October 2013. The HR was recorded by the ECG sensor, placed over the abdomen immediately after birth. RESULTS: Fifty-five newborns were included. The median time from birth to placement of the HR sensor was 3 s (quartiles: 2 and 5), and the median time to the start of breathing was 6 s (quartiles: 2 and 15). The HR was around 120 beats/min (bpm) in the first seconds of life. As determined via breakpoint analysis, the HR increased by 1 beat in the first 40 s to 149 +/- 33 bpm, followed by a moderate increase until 130 s and stabilization thereafter. After the onset of breathing, the HR decreased for 10 s and then increased. Minimal HR changes were observed after cord clamping. CONCLUSION: A dry-electrode ECG sensor detected reliable ECG signals almost immediately after birth. The normal HR increased significantly in spontaneously breathing infants during the first minute, influenced by the onset of breathing. Delayed cord clamping had a minimal impact on the HR, likely reflecting an earlier onset of breathing. PMID- 27250762 TI - Effect of AURKA Gene Expression Knockdown on Angiogenesis and Tumorigenesis of Human Ovarian Cancer Cell Lines. AB - BACKGROUND: Ovarian cancer is one of the most common malignant gynecological cancers. Higher expression of AURKA has been found in immortalized human ovarian epithelial cells in previous studies, implying the relationship between AURKA and ovarian cancer pathogenesis. AIM: We investigated the effect of AURKA on angiogenesis and tumorigenesis of human ovarian cancer cells. METHODS: Firstly, the expression of AURKA in HO8910 and SKOV3 ovarian cancer cell lines was knocked down using a vector expressing a short hairpin small interfering RNA (shRNA). Next, the effect of knockdown of AURKA on cell angiogenesis, proliferation, migration, and invasion was determined by microtubule formation assay, proliferation assay, transwell migration, and invasion assays. In addition, the effect of AURKA knockdown on angiogenesis and tumorigenesis was also determined in a chicken chorioallantoic membrane (CAM) model and in nude mice. RESULTS: The results of the microtubule formation assay indicated that knockdown of AURKA significantly inhibited ovarian cancer cell-induced angiogenesis of endothelial cells compared to its control (P < 0.001). Knockdown of AURKA also significantly inhibited cell proliferation, migration, and invasion of HO8910 and SKOV3 cells in vitro. Furthermore, the Matrigel plug assay showed that knockdown of AURKA significantly repressed ovarian cancer cell-induced angiogenesis in nude mice (P < 0.05), and the CAMs model also showed that AURKA knockdown significantly attenuated the angiogenesis (P < 0.001) and tumorigenesis (P < 0.001) of HO8910 cells compared to the control. Finally, the tumorigenicity assay in vivo further indicated that AURKA shRNA reduced tumorigenesis in nude mice inoculated with ovarian cancer cells (P < 0.001). CONCLUSIONS: These results suggest the potential role of AURKA in angiogenesis and tumorigenesis of ovarian cancer, which may provide a potential therapeutic target for the disease. PMID- 27250764 TI - Insights on dramatic radial fluctuations in track formation by energetic ions. AB - We report on unexpected dramatic radial variations in ion tracks formed by irradiation with energetic ions (2.3 GeV (208)Pb) at a constant electronic energy loss (~42 keV/nm) in pyrochlore-structured Gd2TiZrO7. Though previous studies have shown track formation and average track diameter measurements in the Gd2TixZr(1-x)O7 system, the present work clearly reveals the importance of the recrystallization process in ion track formation in this system, which leads to more morphological complexities in tracks than currently accepted behavior. The ion track profile is usually considered to be diametrically uniform for a constant value of electronic energy-loss. This study reveals the diameter variations to be as large as ~40% within an extremely short incremental track length of ~20 nm. Our molecular dynamics simulations show that these fluctuations in diameter of amorphous core and overall track diameter are attributed to the partial substitution of Ti atoms by Zr atoms, which have a large difference in ionic radii, on the B-site in pyrochlore lattice. This random distribution of Ti and Zr atoms leads to a local competition between amorphous phase formation (favored by Ti atoms) and defect-fluorite phase formation (favored by Zr atoms) during the recrystallization process and finally introduces large radial variations in track morphology. PMID- 27250763 TI - Evaluation of the Therapeutic Potential of the Novel Isotype Specific HDAC Inhibitor 4SC-202 in Urothelial Carcinoma Cell Lines. AB - BACKGROUND: Targeting of class I histone deacetylases (HDACs) exerts antineoplastic actions in various cancer types by modulation of transcription, upregulation of tumor suppressors, induction of cell cycle arrest, replication stress and promotion of apoptosis. Class I HDACs are often deregulated in urothelial cancer. 4SC-202, a novel oral benzamide type HDAC inhibitor (HDACi) specific for class I HDACs HDAC1, HDAC2 and HDAC3 and the histone demethylase LSD1, shows substantial anti-tumor activity in a broad range of cancer cell lines and xenograft tumor models. AIM: The aim of this study was to investigate the therapeutic potential of 4SC-202 in urothelial carcinoma (UC) cell lines. METHODS: We determined dose response curves of 4SC-202 by MTT assay in seven UC cell lines with distinct HDAC1, HDAC2 and HDAC3 expression profiles. Cellular effects were further analyzed in VM-CUB1 and UM-UC-3 cells by colony forming assay, caspase-3/7 assay, flow cytometry, senescence assay, LDH release assay, and immunofluorescence staining. Response markers were followed by quantitative real-time PCR and western blotting. Treatment with the class I HDAC specific inhibitor SAHA (vorinostat) served as a general control. RESULTS: 4SC-202 significantly reduced proliferation of all epithelial and mesenchymal UC cell lines (IC50 0.15-0.51 MUM), inhibited clonogenic growth and induced caspase activity. Flow cytometry revealed increased G2/M and subG1 fractions in VM-CUB1 and UM-UC-3 cells. Both effects were stronger than with SAHA treatment. CONCLUSION: Specific pharmacological inhibition of class I HDACs by 4SC-202 impairs UC cell viability, inducing cell cycle disturbances and cell death. Combined inhibition of HDAC1, HDAC2 and HDAC3 seems to be a promising treatment strategy for UC. PMID- 27250765 TI - Plasmonic gratings with nano-protrusions made by glancing angle deposition for single-molecule super-resolution imaging. AB - Super-resolution imaging has been advantageous in studying biological and chemical systems, but the required equipment and platforms are expensive and unable to observe single-molecules at the high (MUM) fluorophore concentrations required to study protein interaction and enzymatic activity. Here, a plasmonic platform was designed that utilized an inexpensively fabricated plasmonic grating in combination with a scalable glancing angle deposition (GLAD) technique using physical vapor deposition. The GLAD creates an abundance of plasmonic nano protrusion probes that combine the surface plasmon resonance (SPR) from the periodic gratings with the localized SPR of these nano-protrusions. The resulting platform enables simultaneous imaging of a large area without point-by-point scanning or bulk averaging for the detection of single Cyanine-5 molecules in dye concentrations ranging from 50 pM to 10 MUM using epifluorescence microscopy. Combining the near-field plasmonic nano-protrusion probes and super-resolution technique using localization microscopy, we demonstrate the ability to resolve grain sizes down to 65 nm. This plasmonic GLAD grating is a cost-effective super resolution imaging substrate with potential applications in high-speed biomedical imaging over a wide range of fluorescent concentrations. PMID- 27250766 TI - Hypoxia induced CCL28 promotes angiogenesis in lung adenocarcinoma by targeting CCR3 on endothelial cells. AB - Tumor hypoxia is one of the important features of lung adenocarcinoma. Chemokines might mediate the effects caused by tumor hypoxia. As confirmed in tumor tissue and serum of patients, CC chemokine 28 (CCL28) was the only hypoxia induced chemokine in lung adenocarcinoma cells. CCL28 could promote tube formation, migration and proliferation of endothelial cells. In addition, angiogenesis was promoted by CCL28 in the chick chorioallantoic membrane and matrigel implanted in dorsal back of athymic nude mice (CByJ.Cg-Foxn1(nu)/J). Tumors formed by lung adenocarcinoma cells with high expression of CCL28 grew faster and had a higher vascular density, whereas tumor formation rate of lung adenocarcinoma cells with CCL28 expression knockdown was quite low and had a lower vascular density. CCR3, receptor of CCL28, was highly expressed in vascular endothelial cells in lung adenocarcinoma when examining by immunohistochemistry. Further signaling pathways in endothelial cells, modulated by CCL28, were analyzed by Phosphorylation Antibody Array. CCL28/CCR3 signaling pathway could bypass that of VEGF/VEGFR on the levels of PI3K-Akt, p38 MAPK and PLC gamma. The effects could be neutralized by antibody against CCR3. In conclusion, CCL28, as a chemokine induced by tumor hypoxia, could promote angiogenesis in lung adenocarcinoma through targeting CCR3 on microvascular endothelial cells. PMID- 27250768 TI - Genetically Engineered Phages: a Review of Advances over the Last Decade. AB - Soon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work. PMID- 27250772 TI - Nerve-Adherent Giant Cell Tumors of Tendon Sheath: A New Presentation. AB - BACKGROUND: Tenosynovial giant cell tumors are a group of slowly growing benign neoplasms of synovial membrane of joints, tendons, and bursae. The localized type or giant cell tumor of tendon sheath (GCTTS) is the extra-articular form of tenosynovial giant cell tumors. We describe two patients with a GCTTS, confirmed histologically at the time of surgical resection, that was adherent to peripheral nerves. Rare GCTTS can cause extrinsic compression of major nerves. CASE DESCRIPTIONS: The first patient was a 36-year-old man with a left wrist mass associated with pain and paresthesia in the radial three digits. On ultrasound and magnetic resonance imaging (MRI), the mass appeared arising from the left median nerve with a picture suggestive of an atypical neurogenic tumor; however, the possibility of GCTTS could not be excluded. Intraoperatively, the tumor was adherent to the median nerve without a connection to nearby intercarpal joints. The second patient was a 25-year-old woman with a history of malignant melanoma and an incidentally discovered mass on routine follow-up. MRI of the pelvis showed an ovoid mass related to the right sciatic nerve. The MRI picture was suggestive of a GCTTS, although a benign neurogenic tumor was favored given the anatomic relation to the sciatic nerve. Intraoperatively, the tumor appeared as a nodule implanted on the nerve, and it was easily peeled off. CONCLUSION: We present a new, rare presentation of GCTTS adherent to peripheral nerves with extrinsic compression. We suggest either an implantation mechanism or an unrecognized extrasynovial origin for such tumors. PMID- 27250771 TI - Viable offspring obtained from Prm1-deficient sperm in mice. AB - Protamines are expressed in the spermatid nucleus and allow denser packaging of DNA compared with histones. Disruption of the coding sequence of one allele of either protamine 1 (Prm1) or Prm2 results in failure to produce offspring, although sperm with disrupted Prm1 or Prm2 alleles are produced. Here, we produced Prm1-deficient female chimeric mice carrying Prm1-deficient oocytes. These mice successfully produced Prm1(+/-) male mice. Healthy Prm1(+/-) offspring were then produced by transferring blastocysts obtained via in vitro fertilization using zona-free oocytes and sperm from Prm1(+/-) mice. This result suggests that sperm lacking Prm1 can generate offspring despite being abnormally shaped and having destabilised DNA, decondensed chromatin and a reduction in mitochondrial membrane potential. Nevertheless, these mice showed little derangement of expression profiles. PMID- 27250773 TI - Is Carotid Revascularization Safe for Patients with Concomitant Carotid Stenosis and Intracranial Aneurysms? AB - OBJECTIVE: The safety of carotid revascularization in patients with concomitant extracranial carotid stenosis and cerebral aneurysm is rarely reported. We examine the risk of subarachnoid hemorrhage, aneurysm growth, ipsilateral transient ischemic attack, or stroke after revascularization in patients with both carotid stenosis and cerebral aneurysms. METHODS: A retrospective cohort study of patients with concomitant diagnosis of aneurysm and carotid stenosis evaluated in the neurosurgical department at our institution from 1990 to 2013 was carried out. Patients with both revascularized and nonrevascularized carotid stenosis were included. Demographic and angiographic characteristics, medical history, and treatment outcomes were collected. Comparison was made between the following 2 groups: revascularized carotid stenosis with stent or carotid endarterectomy versus nonrevascularized carotid stenosis. RESULTS: The study cohort consisted of 39 patients with 48 stenotic cervical internal carotid arteries and 51 cerebral aneurysms. Twenty patients (51.3%) underwent carotid endarterectomy/stenting, and 19 (48.7%) were managed medically. Patient characteristics were similar across the 2 groups except for increased severity of carotid stenosis (P < 0.001) and more posterior circulation aneurysms (P = 0.045) in the revascularized group. Ipsilateral stenosis and aneurysm was observed in 9 cases (40.9%) in the revascularized group and in 11 cases (42.3%) in the nonrevascularized group. During average follow-up of 1.62 years, no aneurysm rupture was observed. One ipsilateral stroke occurred in the revascularized group during follow-up, corresponding to an annual risk of 2.0%. One aneurysm enlargement occurred per group, with both located in the posterior circulation. CONCLUSIONS: Our study suggests that revascularization procedures for carotid stenosis should be considered safe and effective in patients with concomitant extracranial carotid occlusive disease and cerebral aneurysms. PMID- 27250774 TI - Rising Vancomycin-Resistant Enterococcus Infections in Hospitalized Children in the United States. AB - OBJECTIVE: Vancomycin-resistant Enterococcus (VRE) is an emerging drug-resistant organism responsible for increasing numbers of nosocomial infections in adults. Few data are available on the epidemiology and impact of VRE infections in children. We hypothesized a significant increase in VRE infections among hospitalized children. Additionally, we predicted that VRE infection would be associated with certain comorbid conditions and increased duration and cost of hospitalization. METHODS: A retrospective study of inpatient pediatric patients was performed using data on hospitalizations for VRE from the Healthcare Cost and Utilization Project Kids' Inpatient Database from 1997 to 2012. We used a multivariable logistic regression model to establish factors associated with VRE infection and a high-dimensional propensity score match to evaluate death, length of stay, and cost of hospitalization. RESULTS: Hospitalizations for VRE infection showed an increasing trend, from 53 hospitalizations per million in 1997 to 120 in 2012 (P < .001). Conditions associated with VRE included Clostridium difficile infection and other diagnoses involving immunosuppression and significant antibiotic and health care exposure. Patients with VRE infection had a significantly longer length of stay (attributable difference [AD] 2.1 days, P < .001) and higher hospitalization costs (AD $8233, P = .004). VRE infection was not associated with an increased risk of death (odds ratio 1.03; 95% confidence interval 0.73-1.47). CONCLUSIONS: VRE infections among hospitalized children are increasing at a substantial rate. This study demonstrates the significant impact of VRE on the health of pediatric patients and highlights the importance of strict adherence to existing infection control policies and VRE surveillance in certain high-risk pediatric populations. PMID- 27250769 TI - The Epigenetic Pathways to Ribosomal DNA Silencing. AB - Heterochromatin is the transcriptionally repressed portion of eukaryotic chromatin that maintains a condensed appearance throughout the cell cycle. At sites of ribosomal DNA (rDNA) heterochromatin, epigenetic states contribute to gene silencing and genome stability, which are required for proper chromosome segregation and a normal life span. Here, we focus on recent advances in the epigenetic regulation of rDNA silencing in Saccharomyces cerevisiae and in mammals, including regulation by several histone modifications and several protein components associated with the inner nuclear membrane within the nucleolus. Finally, we discuss the perturbations of rDNA epigenetic pathways in regulating cellular aging and in causing various types of diseases. PMID- 27250775 TI - Occupational therapy in Australian acute hospitals: A modified practice. AB - BACKGROUND/AIM: Ongoing changes to health-care funding Australia wide continue to influence how occupational therapists practise in acute hospitals. This study describes the practice challenges experienced by Western Australian acute care occupational therapists. Then, it explores if and how acute care occupational therapists are modifying their practice in response to these practice changes. METHODOLOGY: This study used a qualitative grounded theory approach. Semi structured interviews were completed with 13 purposively selected acute care occupational therapists from four Western Australian metropolitan hospitals. Data were analysed using a constant comparative method to provide detailed descriptions of acute care occupational therapy practice and to generate theory. FINDINGS: Five conceptual categories were developed. The first two addressed practice challenges: pragmatic organisational influences on client care and establishing a professional identity within the multidisciplinary team. Three categories related to therapist responses are as follows: becoming the client advocate, being the facilitator and applying clinical reasoning. Finally, modified practice was identified as the core category which explains the process whereby acute care occupational therapists are ensuring they remain relevant and authentic in the acute care context. CONCLUSION: Western Australian acute care occupational therapists are practising in a highly complex health context that presents many challenges. They are responding by using a modified form of practice that ensures occupational therapy skills remain relevant within the narrow confines of this health setting. PMID- 27250777 TI - Effective Topological Charge Cancelation Mechanism. AB - Topological defects (TDs) appear almost unavoidably in continuous symmetry breaking phase transitions. The topological origin makes their key features independent of systems' microscopic details; therefore TDs display many universalities. Because of their strong impact on numerous material properties and their significant role in several technological applications it is of strong interest to find simple and robust mechanisms controlling the positioning and local number of TDs. We present a numerical study of TDs within effectively two dimensional closed soft films exhibiting in-plane orientational ordering. Popular examples of such class of systems are liquid crystalline shells and various biological membranes. We introduce the Effective Topological Charge Cancellation mechanism controlling localised positional assembling tendency of TDs and the formation of pairs {defect, antidefect} on curved surfaces and/or presence of relevant "impurities" (e.g. nanoparticles). For this purpose, we define an effective topological charge Deltameff consisting of real, virtual and smeared curvature topological charges within a surface patch Deltasigma identified by the typical spatially averaged local Gaussian curvature K. We demonstrate a strong tendency enforcing Deltameff -> 0 on surfaces composed of Deltasigma exhibiting significantly different values of spatially averaged K. For Deltameff ? 0 we estimate a critical depinning threshold to form pairs {defect, antidefect} using the electrostatic analogy. PMID- 27250778 TI - A new hydrophilic supramolecular photocatalyst for the production of H2 in aerobic aqueous solutions. AB - Addition of sulfonated terminal ligands into a Ru,Rh,Ru photocatalyst has a significant impact on the excited-state properties of the complex. The hydrophilic photocatalyst demonstrates increased solubility and H2 production in aqueous solutions. H2 production is observed under aerobic conditions for the new complex, a stark contrast to the hydrophobic analog in organic solvents. PMID- 27250779 TI - [A strategy for health and safety at work]. PMID- 27250776 TI - Concise Review: Measuring Physiological Responses of Human Pluripotent Stem Cell Derived Cardiomyocytes to Drugs and Disease. AB - Cardiomyocytes from human pluripotent stem cells (hPSC) are of growing interest as models to understand mechanisms underlying genetic disease, identify potential drug targets and for safety pharmacology as they may predict human relevant effects more accurately and inexpensively than animals or other cell models. Crucial to their optimal use are accurate methods to quantify cardiomyocyte phenotypes accurately and reproducibly. Here, we review current methods for determining biophysical parameters of hPSC-derived cardiomyocytes (hPSC-CMs) that recapitulate disease and drug responses. Even though hPSC-CMs as currently available are immature, various biophysical methods are nevertheless already providing useful insights into the biology of the human heart and its maladies. Advantages and limitations of assays currently available looking toward applications of hPSC-CMs are described with examples of how they have been used to date. This will help guide the choice of biophysical method to characterize healthy cardiomyocytes and their pathologies in vitro. Stem Cells 2016;34:2008 2015. PMID- 27250770 TI - Plasticity of Candida albicans Biofilms. AB - Candida albicans, the most pervasive fungal pathogen that colonizes humans, forms biofilms that are architecturally complex. They consist of a basal yeast cell polylayer and an upper region of hyphae encapsulated in extracellular matrix. However, biofilms formed in vitro vary as a result of the different conditions employed in models, the methods used to assess biofilm formation, strain differences, and, in a most dramatic fashion, the configuration of the mating type locus (MTL). Therefore, integrating data from different studies can lead to problems of interpretation if such variability is not taken into account. Here we review the conditions and factors that cause biofilm variation, with the goal of engendering awareness that more attention must be paid to the strains employed, the methods used to assess biofilm development, every aspect of the model employed, and the configuration of the MTL locus. We end by posing a set of questions that may be asked in comparing the results of different studies and developing protocols for new ones. This review should engender the notion that not all biofilms are created equal. PMID- 27250780 TI - [The UNIPSICO questionnaire: psychometric properties of the scales measuring psychosocial demands]. AB - PURPOSE: To analyze the psychometric properties of the UNIPSICO questionnaire' scales designed to evaluate psychosocial demands at work. METHODS: The sample consisted of 2564 participants; 1391 were employees working with persons with intellectual disabilities and 1173 high school teachers from the Valencian Community. Data were collected using the UNIPSICO questionnaire, which features scales designed to measures psychosocial demands at work. This instrument contains 27 items distributed in 5 scales: interpersonal conflicts, imbalance, role conflict, role ambiguity, and workload. Data were analysed to test item validity, construct validity by confirmatory factor analysis (CFA), reliability by Cronbach's alpha, and predictive validity by stepwise regression analysis. RESULTS: For all items, skewness and reliability were adequate. The five scales followed a normal distribution, with skewness values ranging between +1 and -1. The results of the CFA confirmed the hypothesised five-factor structure. The hypothesised model obtained a good data fit (GFI = 0,935, NNFI = 0,903, CFI = 0,914, RMSEA = 0,050). Scale score reliability coefficients for the five scales showed values above 0.70. Stepwise regression analysis demonstrated all variables to be significant predictors of psychosomatic disorders. CONCLUSIONS: The validity and reliability of the five scales were satisfactory. In addition, the scales offer predictive validity for measuring work-related psychosomatic disorders. The UNIPSICO scales analyzed are an adequate tool for the evaluation of psychosocial risk factors at work. PMID- 27250781 TI - [The UNIPSICO questionnaire: psychometric properties of the scales measuring psychosocial resource factors]. AB - PURPOSE: To analyze the psychometric properties of the UNIPSICO questionnaire' scales designed to evaluate psychosocial resource factors at work. METHODS: The sample consisted of 2564 participants; 1391 were employees working with people with intellectual disability and 1173 were high school teachers from the Valencian Community. Data were collected through use of the UNIPSICO questionnaire, which includes scales designed to measure psychosocial resource factors in the workplace. This instrument consists of 26 items distributed in 4 scales: resources at work, work social support, feedback, and autonomy. Data were analysed to test item validity, construct validity by confirmatory factor analysis (CFA), reliability by Cronbach's alpha, and predictive validity by stepwise regression analysis. RESULTS: For all items skewness and reliability values were adequate. The four scales followed the normal distribution, with skewness values ranging between +1 and -1. The results of the CFA confirmed the hypothesised four-factor structure. The hypothesised model showed a good data fit (GFI = 0,922, NNFI = 0,898, CFI = 0,912, RMSEA = 0,059). Scale score reliability coefficients for the five scales showed values above 0.80. Stepwise regression analysis demonstrated all variables were significant predictors of psychosomatic disorders. CONCLUSIONS: The validity and reliability of the four scales were satisfactory. In addition, the scales offer predictive validity for the study of work-related psychosomatic disorders. The UNIPSICO scales analyzed are an adequate tool to evaluate psychosocial resource factors at work. PMID- 27250782 TI - [The application of causal diagrams to conceptualize mechanisms in occupational epidemiology]. AB - Although a goal of epidemiological research is to identify causal relationships between a risk factor and a health problem, the methodology employed often sacrifices internal validity to gain capacity to detect associations. There are new graphical and statistical methods that can help unravel the possible causal mechanisms and better understand this "black box". This paper presents causal diagrams, one of the most useful tools for mapping out, prior to analysis, whether a possible association is causal or just due to bias. To demonstrate its usefulness, we use occupational health examples, showing how associations may arise through non-causal pathways as a result of bias. In conclusion, we recommend the routine practice of using causal diagrams in epidemiological research. PMID- 27250783 TI - [A comparison of two simplified methods of exposure risk assesment of inhalation of chemical agents: the COSHH essentials method and the INRS-based method]. PMID- 27250784 TI - [Response: "Should psychosocial risk factors associated with working conditions be evaluated?"]. PMID- 27250785 TI - [Response: "Should psychosocial risk factors associated with working conditions be evaluated?"]. PMID- 27250786 TI - Improving efficiency and color purity of poly(9,9-dioctylfluorene) through addition of a high boiling-point solvent of 1-chloronaphthalene. AB - In this work, the beta-phase of poly(9,9-dioctylfluorene) (PFO) was used as a probe to study the effects of the addition of a high boiling-point solvent of 1 chloronaphthalene on the nanostructures and electroluminescence of PFO films. Both absorption and photoluminescence spectra showed that the content of the beta phase in PFO film was obviously enhanced as a result of the addition of a small amount of 1-chloronaphthalene into the processing solvent of p-xylenes. Apparently rougher morphology associated with the effectively enhanced ordering of polymer chains across the entire film was observed for films processed from p xylene solutions consisting of a certain amount of 1-chloronaphthalene, as revealed by atomic force microscopy and grazing incidence x-ray diffraction measurements. In addition to the effects on the nanostructures of films, of particular interest is that the performance and color purity of polymer light emitting devices can be noticeably enhanced upon the addition of 1 chloronaphthalene. These observations highlight the importance of controlling the nanostructures of the emissive layer, and demonstrate that the addition of a low volume ratio of high boiling-point additive can be a promising strategy to attain high-performance polymer light-emitting diodes. PMID- 27250787 TI - Development of Tetranuclear Zinc Cluster-Catalyzed Environmentally Friendly Reactions and Mechanistic Studies. AB - Our studies on tetranuclear zinc cluster-catalyzed environmentally friendly reactions are presented here. The newly developed MU-oxo-tetranuclear zinc cluster is a highly efficient catalyst for the direct formation of oxazolines from esters, carboxylic acids, lactones, and nitriles; for the transesterification of various methyl esters including alpha-amino esters and beta-keto esters; for the acetylation of alcohols in EtOAc; and for the deacylation of esters in MeOH. A unique hydroxy group-selective acylation in the presence of inherently much more nucleophilic amino groups was also achieved by this zinc cluster. Zinc cluster-catalyzed transesterification, in particular, was drastically accelerated by the addition of alkyl amine and N-heteroaromatic ligands, which coordinate with the metals, stabilize the clusters with lower nuclearities, and enhance catalytic activity for the transesterification. We also performed several mechanistic studies which revealed that alkoxide metal complexes are the active species in this catalytic cycle, and that the Michaelis Menten behavior of the complexes through an ordered ternary complex mechanism is similar to that of dinuclear metalloenzymes. The deprotonation of nucleophiles was the most important step in this process, not only for achieving high catalytic activity but also for determining chemoselectivity, resulting in the chemical differentiation of alcohols and amines. PMID- 27250788 TI - BET Bromodomain as a Target of Epigenetic Therapy. AB - Acetylation of histone is a key epigenetic modification, and contributes to many DNA-dependent cellular processes. The bromodomain structure, which consists of approximately 110 amino acid residues, serves as a 'reader' that recognizes acetylated lysine in histones, leading to recruitment of positive transcriptional elongation factor b (P-TEFb), and thereby promoting transcriptional activity and chromatin remodeling. Among bromodomain-containing proteins, members of the bromodomain and extra-terminal domain (BET) family contain tandem N-terminal bromodomains. BET proteins, especially BRD4, have attracted interest as candidate therapeutic targets due to their putative involvement in the pathogenesis of various diseases, including cancer and inflammatory diseases. Several BET inhibitors are under clinical trial for treatment of various cancers. Furthermore, polypharmacological agents such as dual kinase/BET inhibitors and dual histone deacetylase (HDAC)/BET inhibitors have recently been developed, in addition to agents that degrade BET family proteins, such as proteolysis targeting chimeras (PROTACs). This paper reviews recent progress in epigenetic therapy targeting the BET bromodomain. PMID- 27250789 TI - Role of Vitamin C in Cardioprotection of Ischemia/Reperfusion Injury by Activation of Mitochondrial KATP Channel. AB - How to provide effective prevention and treatment of myocardial ischemia/reperfusion (I/R) injury and study of the mechanism underlying I/R injury are hotspots of current research. This study aimed to elucidate the effect and cardioprotective mechanism of vitamin C (VC) on myocardial I/R injury. Our study introduced two different I/R models: I/R in vitro and oxygen-glucose deprivation/recovery (OGD/R) in primary neonatal rat cardiac myocytes. We used the mitochondrial permeability transition pore (mPTP) opener lonidamine (LND) and the mitochondrial KATP (mitoKATP) channel inhibitor 5-hydroxydecanoate (5-HD) to analyze the underlying mechanisms. We found that post-treatment with VC decreased I/R injury in our models. Post-treatment with VC significantly decreased I/R induced injury, attenuated apoptosis, and maintained the functional integrity of mitochondria via alleviation of Ca(2+) overload, reactive oxygen species burst, inhibition of the opening of mPTP, and prevention of mitochondrial membrane potential (DeltaPsim) depolarization. VC post-treatment increased the phosphorylation of Akt and glycogen synthase kinase (GSK)-3beta. The present results demonstrate that VC might protect the myocardium from I/R-induced injury by inhibiting the mPTP opening via activation of mitoKATP channels. VC mediates cardioprotection via activation of the phosphatidyl inositol 3-kinase (PI3K)-Akt signaling pathway. These findings may contribute toward the development of novel strategies for clinical cardioprotection against I/R injury. PMID- 27250790 TI - Synthesis, in Vivo Anti-inflammatory, and in Vitro Antimicrobial Activity of New 5-Benzofuranyl Fused Pyrimidines. AB - Chalcone (3) has been synthesized as a new chalcone derivative bearing benzofuran moiety at 1 position. Such chalcone was used as a model dielectrophile applied to react with some nucleophiles such as 5-amino pyrazoles, 5-amino-1,2,4-triazole, 2 aminobenzimidazole, and 6-uraciles under Michael reaction conditions and resulted in a new series of fused pyrimidines such as pyrazolo[1,5-a]pyrimidines 7a-e, [1,2,4]-triazolo[1,5-a]pyrimidine 9, pyrimido[1,2-a]benzimidazole 11, and synthesis of pyrido[2,3-d]pyrimidinones 13a and b. The structures of the synthesized target heterocyclic compounds were confirmed by microanalytical and spectral data such as Fourier transform (FT)-IR, (1)H-NMR, and MS spectra. The newly synthesized compounds were evaluated for their anti-inflammatory and antimicrobial activities; most showed significant activities. PMID- 27250791 TI - Highly Efficient Synthesis of Chalcones from Poly Carbonyl Aromatic Compounds Using BF3-Et2O via a Regioselective Condensation Reaction. AB - A new, simple, highly efficient method for the synthesis of different types of carbonyl chalcones through a regioselective condensation reaction of appropriate 5-acetyl-2-hydroxybenzaldehyde with various substituted acetophenones and 4 hydroxyisothalaldehyde with various substituted aldehydes using BF3-Et2O as a reagent is described. PMID- 27250792 TI - Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing alpha-Monoglyceride Additives. AB - SN-38 is a potent active metabolite of irinotecan that has been considered as an anticancer candidate. However, the clinical development of this compound has been hampered by its poor aqueous solubility and chemical instability. In this study, we developed SN-38-encapsulated cubosomes to resolve these problems. Six alpha monoglyceride additives, comprising monocaprylin, monocaprin, monolaurin, monomyristin, monopalmitin, and monostearin, were used to prepare phytantriol (PHYT) cubosomes by probe sonication. The mean particle size, polydispersity index, and zeta potential values of these systems were around 190-230 nm, 0.19 0.25 and -17 to -22 mV, respectively. Small-angle X-ray scattering analyses confirmed that the SN-38-encapsulated cubosomes existed in the Pn3m space group both with and without the additives. The monoglyceride additives led to around a two-fold increase in the solubility of SN-38 compared with the PHYT cubosome. The drug entrapment efficiency of PHYT cubosomes with additives was greater than 97%. The results of a stability study at 25 degrees C showed no dramatic changes in the particle size or polydispersity index characteristics, with at least 85% of the SN-38 existing in its active lactone form after 10 d, demonstrating the high stability of the cubosome nanoparticles. Furthermore, approximately 55% of SN-38 was slowly released from the cubosomes with additives over 96 h in vitro under physiological conditions. Taken together, these results show that the SN-38 encapsulated PHYT cubosome particles are promising drug carriers that should be considered for further in vivo experiments, including drug delivery to tumor cells using the enhanced permeability and retention effect. PMID- 27250793 TI - Intracellular Metabolism of alpha,beta-Unsaturated Carbonyl Compounds, Acrolein, Crotonaldehyde and Methyl Vinyl Ketone, Active Toxicants in Cigarette Smoke: Participation of Glutathione Conjugation Ability and Aldehyde-Ketone Sensitive Reductase Activity. AB - The major toxicants in cigarette smoke, alpha,beta-unsaturated aldehydes, such as acrolein (ACR) and crotonaldehyde (CA), and alpha,beta-unsaturated ketone, methyl vinyl ketone (MVK), are known to form Michael-type adducts with glutathione (GSH) and consequently cause intracellular GSH depletion, which is involved in cigarette smoke-induced cytotoxicity. We have previously clarified that exposure to cigarette smoke extract (CSE) of a mouse melanoma cell culture medium causes rapid reduction of intracellular GSH levels, and that the GSH-MVK adduct can be detected by LC/MS analysis while the GSH-CA adduct is hardly detected. In the present study, to clarify why the GSH-CA adduct is difficult to detect in the cell medium, we conducted detailed investigation of the structures of the reaction products of ACR, CA, MVK and CSE in the GSH solution or the cell culture medium. The mass spectra indicated that in the presence of the cells, the GSH-CA and GSH-ACR adducts were almost not detected while their corresponding alcohols were detected. On the other hand, both the GSH-MVK adducts and their reduced products were detected. In the absence of the cells, the reaction of GSH with all alpha,beta-unsaturated carbonyls produced only their corresponding adducts. These results show that the GSH adducts of alpha,beta-unsaturated aldehydes, CA and ACR, are quickly reduced by certain intracellular carbonyl reductase(s) and excreted from the cells, unlike the GSH adduct of alpha,beta-unsaturated ketone, MVK. Such a difference in reactivity to the carbonyl reductase might be related to differences in the cytotoxicity of alpha,beta-unsaturated aldehydes and ketones. PMID- 27250794 TI - Design, Synthesis and Evaluation of New Fluoroamodiaquine Analogues. AB - Malaria is one of the most important tropical diseases; the use of amodiaquine as a current chemotherapy in the treatment of malaria has shown some problems such as hepatotoxicity and agranulocytosis. In this work we present the rational design, synthesis, and biological evaluation (antimalarial activity, cytotoxicity and genotoxicity) of four new fluoroamodiaquine analogues. The results showed significant correlation between MolDock score and IC50 values. The molecules 7b and c were the most active of the planned compounds, with lower IC50 against Plasmodium falciparum W2 strain (0.9 and 0.8 uM, respectively) and an excellent cytotoxicity profile. The present study revealed no mutagenicity or genotoxicity for the analogues. Confirming our docking results, the molecular dynamics showed that compound 7b remains stably bound to the heme group by means of pi-stacking interactions between quinoline and the porphyrin ring. Based on these findings, this study may prove to be an efficient approach for the rational design of hemozoin inhibiting compounds to treat malaria. PMID- 27250795 TI - Identification of Cyclopropylacetyl-(R)-carnitine, a Unique Chemical Marker of the Fatally Toxic Mushroom Russula subnigricans. AB - A toxic mushroom, Russula subnigricans, causes fatal poisoning by mistaken ingestion. In spite of the potent bioactivity, the responsible toxin had not been identified for about 50 years since its first documentation. Recently, we isolated an unstable toxin and determined the structure. The slow elucidation was partly due to the instability of the toxin and also due to misidentification of R. subnigricans for similar mushrooms. To discriminate genuine Russula subnigricans from similar unidentified Russula species, we searched for a unique chemical marker contained in the mushroom. Cyclopropylacetyl-(R)-carnitine specific to R. subnigricans was identified as a novel compound whose (1)H-NMR signals appearing in the upfield region were easily recognizable among the complicated signals of the crude extract. PMID- 27250796 TI - Synthesis and in Vitro Antifungal Activities of Novel Benzamide Derivatives Containing a Triazole Moiety. AB - The study reported the synthesis and antifungal activities in vitro against six phytopathogenic fungi of 17 novel N-[2-hydroxy-3,3-dimethyl-2-[(1H-1,2,4-triazol 1-yl)methyl]butyl]benzamide derivatives. All the target compounds were synthesized and elucidated by means of MS, high resolution (HR)-MS, IR, (1)H- and (13)C-NMR analysis. The results showed that almost all the derivatives exhibited good activities against each of the tested fungi at the concentration of 50 ug/mL. Among them, 6h displayed excellent activity against Alternaria alternata with the median effective concentration value (EC50) of 1.77 ug/mL, superior to myclobutanil (EC50=6.23 ug/mL), a commercial fungicide with broad-spectrum bioactivities for plant protection and high-efficiency. Compound 6k showed the broadest antifungal spectrum, demonstrating positive activities against the corresponding fungi with EC50 values ranging from 0.98 to 6.71 ug/mL. Furthermore, 6e to 6i revealed good activities against Alternaria solani with EC50 values of 1.90, 4.51, 7.07, 2.00 and 5.44 ug/mL, respectively. The preliminary analysis of structure-activity relationship (SAR) demonstrated that the presence of F or Cl on the benzene ring remarkably improved the activity, while the introduction of 4-OMe or CF3 group decreased the activity in varying degrees. Thus, the present results strongly suggest that N-[2-hydroxy-3,3 dimethyl-2-[(1H-1,2,4-triazol-1-yl)methyl]butyl]benzamide derivatives should be promising candidates for the development of novel antifungal agents in the effective control of phytopathogenic fungi. PMID- 27250797 TI - Polycyclic Aromatic Hydrocarbons in Surface Water of the Southeastern Japan Sea. AB - Surface water samples were collected at 15 sampling sites in the southeastern Japan Sea along the Japanese Archipelago for analysis of polycyclic aromatic hydrocarbons (PAHs). Water samples were fractionated by filtration through a glass fiber membrane (pore size 0.5 um) and analyzed by high-performance liquid chromatography with fluorescence detection. Thirteen PAHs having 3 to 6 rings were found in the dissolved phase (DP) and 12 were found in the particulate phase (PP). The total (DP+PP) PAH concentration ranged from 6.83 to 13.81 ng/L with the mean+/-standard deviation (S.D.) concentration of 9.36+/-1.92 ng/L. The mean+/ S.D. PAH concentration in the DP and PP was 5.99+/-1.80 and 3.38+/-0.65 ng/L, respectively. Three-ring PAHs predominated in the DP, while the proportion of 4 ring PAHs was higher in the PP. The mean total PAH concentration in the southeastern Japan Sea was higher than the concentration in the northwestern Japan Sea (8.5 ng/L). The Tsushima Current, which originates from the East China Sea with higher PAH concentration, is considered to be responsible for this higher concentration. PMID- 27250798 TI - Sulfated Glucosides of an Aliphatic Alcohol and Monoterpenes, and Megastigmanes from the Leaves of Meliosma pinnata spp. arnottiana. AB - Chemical study of the leaves of Meliosma pinnata spp. arnottiana afforded five sulfated glucosides of oct-1-en-3-ol (1) and cyclic linalool derivatives (2-5), and two megastigmanes (6, 7). Their structures were elucidated by extensive investigation of one- and two-dimensional NMR spectroscopic data, and the absolute structures of the megastigmanes were determined by the modified Mosher's method. PMID- 27250799 TI - Preparation of Fine Particles with Improved Solubility Using a Complex Fluidized Bed Granulator Equipped with a Particle-Sizing Mechanism. AB - A new type of fluidized-bed granulator equipped with a particle-sizing mechanism was used for the preparation of fine particles that improved the solubility of a poorly water-soluble drug substance. Cefteram pivoxyl (CEF) was selected as a model drug substance, and its solution with a hydrophilic polymer, hydroxypropyl cellulose (HPC-L), was sprayed on granulation grade lactose monohydrate (Lac). Three types of treated particles were prepared under different conditions focused on the spraying air pressure and the amount of HPC-L. When the amount of HPC-L was changed, the size of the obtained particles was similar. However, particle size distribution was dependent on the amount of HPC-L. Its distribution became more homogenous with greater amounts of HPC-L, but the particle size distribution obtained by decreasing the spraying air pressure was not acceptable. By processing CEF with HPC-L using a complex fluidized-bed granulator equipped with a particle-sizing mechanism, the dissolution ratio was elevated by approximately 40% compared to that of unprocessed CEF. Moreover, in the dissolution profile of treated CEF, the initial burst was suppressed, and nearly zero order release was observed up to approximately 60% in the dissolution profile. This technique may represent a method with which to design fine particles of approximately 100 um in size with a narrow distribution, which can improve the solubility of a drug substance with low solubility. PMID- 27250800 TI - In Vitro Transformation of Chlorinated Parabens by the Liver S9 Fraction: Kinetics, Metabolite Identification, and Aryl Hydrocarbon Receptor Agonist Activity. AB - We investigated the kinetics of in vitro transformation of a dichlorinated propyl paraben (2-propyl 3,5-dichloro-4-hydroxybenzoate; Cl2PP) by the rat liver S9 fraction and assessed the aryl hydrocarbon receptor (AhR) agonist activity of the metabolite products identified in HPLC and GC/MS analysis and by metabolite syntheses. The results indicated that the chlorination of Cl2PP reduced its degradation rate by approximately 40-fold. Two hydroxylated metabolite products showed AhR agonist activity of up to 39% of that of the parent Cl2PP when assessed in a yeast (YCM3) reporter gene assay. The determination of the metabolic properties of paraben bioaccumulation presented here provides further information on the value of risk assessments of chlorinated parabens as a means to ensure human health and environmental safety. PMID- 27250801 TI - Endocrine prevention of chemotherapy-induced ovarian failure. PMID- 27250804 TI - Targeting CD1c-expressing classical dendritic cells to prevent thymus and activation-regulated chemokine (TARC)-mediated T-cell chemotaxis in rheumatoid arthritis. AB - OBJECTIVES: Thymus and activation-regulated chemokine (TARC) attracts cells that express the C-C chemokine receptor type 4 (CCR4), including CD4 T cells. As expression of CCR4 is increased on peripheral T cells and intra-articular interleukin (IL)-17-producing cells in patients with rheumatoid arthritis (RA), we investigated whether TARC plays a role in the attraction of T cells to the synovial compartment. In addition, we assessed the role of classical dendritic cells (cDCs) in the production of TARC in RA. METHOD: TARC was measured in synovial fluid (SF) samples from RA and osteoarthritis (OA) patients. Spontaneous and thymic stromal lymphopoietin (TSLP)-induced TARC production by mononuclear cells (MCs) and CD1c cDCs from peripheral blood (PB) and SF was assessed. The role of TARC in CD4 T-cell migration towards cDCs was assessed and the contribution of CD1c-expressing cells to TARC production was studied. RESULTS: TARC concentrations were higher in SF of RA patients compared to OA patients. MCs from SF produced TARC spontaneously and produced more TARC upon stimulation than paired PBMCs. Blocking TARC strongly inhibited CD4 T-cell chemotaxis by TSLP stimulated cDCs, associated with decreased production of tumour necrosis factor (TNF)-alpha. Depletion of cDCs from SFMCs strongly reduced TARC production. CONCLUSIONS: TARC levels are increased in RA SF and our data indicate that this results from production by SFMCs and in particular CD1c cDCs. TARC attracts T cells and TARC secretion by MCs is crucially dependent on the presence of CD1c cDCs. Considering the potential of SF cDCs to activate T cells and induce pro inflammatory cytokine secretion, targeting intra-articular cDCs constitutes a novel therapeutic approach in RA. PMID- 27250805 TI - Fishes and aquatic habitats of the Orinoco River Basin: diversity and conservation. AB - About 1000 freshwater fishes have been found so far in the Orinoco River Basin of Venezuela and Colombia. This high ichthyological diversity reflects the wide range of landscapes and aquatic ecosystems included in the basin. Mountain streams descend from the high Andes to become rapid-flowing foothill rivers that burst out upon vast savannah flatlands where they slowly make their way to the sea. These white-water rivers are heavily laden with sediments from the geologically young Andes. Because their sediment deposits have formed the richest soils of the basin, they have attracted the highest density of human populations, along with the greatest levels of deforestation, wildfires, agricultural biocides and fertilizers, sewage and all the other impacts associated with urban centres, agriculture and cattle ranching. In the southern portion of the basin, human populations are much smaller, where often the only inhabitants are indigenous peoples. The ancient rocks and sands of the Guiana Shield yield clear and black water streams of very different quality. Here, sediment loads are miniscule, pH is very acid and fish biomass is only a fraction of that observed in the rich Andean tributaries to the north. For each region of the basin, the current state of knowledge about fish diversity is assessed, fish sampling density evaluated, the presence of endemic species and economically important species (for human consumption or ornamental purposes) described and gaps in knowledge are pointed out. Current trends in the fishery for human consumption are analysed, noting that stocks of many species are in steep decline, and that current fishing practices are not sustainable. Finally, the major impacts and threats faced by the fishes and aquatic ecosystems of the Orinoco River Basin are summarized, and the creation of bi-national commissions to promote standardized fishing laws in both countries is recommended. PMID- 27250802 TI - Short Communication: Maraviroc Once-Daily: Experience in Routine Clinical Practice. AB - To assess the efficacy and safety of maraviroc (MVC) administered once-daily in routine clinical practice. A retrospective multicenter study (27 centers in Spain) was conducted. Data were collected from the records of patients starting a regimen with MVC. Laboratory and clinical data were recorded every 3 months the first year and every 6 months thereafter. Data are presented as median and interquartile range. Among 667 patients treated with MVC, 142 (21.3%) received MVC once-daily: 108 (76.1%), 150 mg and 34 (23.9%), and 300 mg. Age was 47 (42 45) years, there were 76.1% men, and 81 (57%) patients had baseline HIV-RNA <50 copies/mL. Viral tropism was R5 in 118 (83.1%) patients. Reasons for prescribing MVC: salvage therapy (36.6%), drug toxicity (31.2%), simplification (16.9%), and immunodiscordant response (7.1%). Median follow-up was 13 (9-16) months. In 95.8%, a PI/r was part of the regimen (67% on dual therapy). At months 12 and 24, 73.3% and 68.2% of patients had HIV-RNA <50 copies/mL, respectively (p = .041 and p < .001 vs. baseline). CD4+ cell count increased by a median of 52 (-36,135) and 84 (-9.5,180) cells/mm3 at 12 and 24 months, respectively (p < .001 and p = .039 vs. baseline). Twenty-five (17.6%) patients discontinued MVC: virologic failure (6), medical decision (5), and other reasons (14). Two patients presented grade 3 adverse events (hypertransaminasemia, hypertriglyceridemia) without the need for MVC withdrawal, whereas MVC was discontinued in two patients due to gastrointestinal toxicity. In routine clinical practice, MVC once-daily combined with at least PI/r was virologically effective and well tolerated in a high percentage of pretreated patients. PMID- 27250806 TI - REACTED - Reducing Acute Chest pain Time in the ED: A prospective pre-/post interventional cohort study, stratifying risk using early cardiac multi-markers, probably increases discharges safely. AB - OBJECTIVE: ED chest pain assessments can be challenging, lengthy and contribute to overcrowding. Rapid accurate risk stratification strategies should improve ED length of stay (EDLOS). Emergency, Biochemistry and Cardiology implemented new guidelines using paired (<3 h) multiple cardiac markers to stratify patients. The intervention would reduce chest pain EDLOS. We observed for safety and disposition effects. METHODS: This is a single-site, prospective observational, before and after intervention study. In December 2009, paired multiple cardiac markers, the second at least 4 h from pain, replaced late troponins. The 4 h rule (ED flow improvement) started in April 2009 (unplanned confounder). Demographics, clinical features, risk assessment and disposition; preferably prospective. Administrative datasets provided disposition outcomes, 4 months pre-/post intervention. Follow up with partially blinded adjudications assessed for 45 day major adverse cardiac events (MACE). Before intervention, consecutive patients were enrolled with mixed prospective/retrospective data. After, sampling occurred whenever prospective data were collected. RESULTS: Adjudicated patients were n = 1029 (14.2% MI, 14.9% MACE), 426 before, 603 after. EDLOS reduced 87 min (416 329; P < 0.001), similar to triage 2 patients without chest pain. Possibly, avoidable MACE occurred in five of 598 discharges (0.8%, CI 0.3-1.8%) with non significant decreases (0.5%, CI 0.1-1.8%) post-intervention. Disposition changes included greater observation ward use (3.8-12.3%; P < 0.001), more discharges (47.4-52.9%, P = 0.002), less transfers (9.3-6.9%, P = 0.014) and less late inpatient discharge decisions (15.2-8.7%, P = 0.001). CONCLUSION: Paired cardiac markers performed adequately for avoidable MACE, and disposition improved significantly. A confounding system change meant the reduced EDLOS (primary outcome) was unable to be associated with the intervention. PMID- 27250807 TI - Sleep Pathology in Creutzfeldt-Jakob Disease. AB - STUDY OBJECTIVES: Associations between sleep and neurodegenerative diseases have become increasingly evident. This study aims to characterize the prevalence and type of sleep pathology in Creutzfeldt-Jakob disease (CJD), a rapidly progressive, fatal neurodegenerative disease. METHODS: In this observational cross-sectional cohort study, we performed a retrospective analysis of sleep signs and symptoms in a consecutive group of patients with definite CJD at a tertiary care medical center (n = 28). Polysomnography was performed in 14 patients. RESULTS: Although only 5 of 28 patients carried a premorbid sleep diagnosis, signs/symptoms of sleep pathology were present in 25 patients. Eleven reported hypersomnia whereas 13 reported insomnia. Seven had restless legs symptoms and/or periodic limb movements of sleep, and nine reported parasomnias. Of the 14 patients who underwent polysomnography, 1 did not show sleep, 9 (69%) had poorly formed or absent sleep spindles and/or K-complexes, and 10 (77%) had sleep-disordered breathing. Of the 8 patients who experienced rapid eye movement (REM) sleep during the polysomnography, 3 (38%) showed REM sleep without atonia, and 2 patients met criteria for REM sleep behavior disorder. Median total sleep time was 226 (interquartile range [IQR] = 195-282) min. Median sleep efficiency was 58.5% (IQR = 41-65.5 %). Median REM time was 0.35% (IQR = 0-7.125%). Five patients (38%) demonstrated periodic limb movements during polysomnography. One case is presented. CONCLUSIONS: Sleep pathology is common in CJD, and screening for sleep pathology is indicated in the evaluation of patients with rapidly progressive dementias. Early identification and treatment of sleep pathology may provide an intervenable target for CJD. PMID- 27250808 TI - Prevalence and Mimics of Kleine-Levin Syndrome: A Survey in French-Speaking Switzerland. AB - STUDY OBJECTIVE: Kleine-Levin syndrome (KLS) is a rare disease of unknown etiology, the diagnosis of which can be challenging. We aimed to estimate KLS prevalence in French-speaking Switzerland, and assess differences with mimicking conditions. METHODS: In this cross-sectional study, KLS patients were identified through a population-based approach, including at our hospital and contacting all sleep-certified facilities and neurologists in French-speaking Switzerland. Furthermore, we identified patients referred to our center for suspected KLS that received other diagnoses. Relevant clinical data of these two groups was compared. RESULTS: We identified 7 patients with diagnosed KLS (6 since 2009), leading to a prevalence estimation of 3.19 per million (95% confidence interval: 1.55-6.59). Median age at diagnosis was 17 years (range: 12-19), 71.4% of them were men, and mean diagnosis delay after the first episode was 20.1 +/- 10.9 months. We identified 9 mimic patients referred to our center; they differed from KLS patients by their higher age at disease onset (median: 15 [range: 12-16] vs. 19 [range: 16-64] years; p < 0.001), suspected KLS as referral reason (more frequent in mimics, p = 0.003), and the presence of precipitating factors (more frequent in KLS, p = 0.011). Among the mimic patients, 77% (versus 28% in KLS) had a psychiatric diagnosis. CONCLUSIONS: This study suggests a relatively higher KLS prevalence than previously reported. As compared to KLS, mimic patients have higher age at symptom onset, are more often initially referred for KLS suspicion, and have a higher prevalence of psychiatric disorders. PMID- 27250809 TI - Recommended Amount of Sleep for Pediatric Populations: A Consensus Statement of the American Academy of Sleep Medicine. AB - ABSTRACT: Sleep is essential for optimal health in children and adolescents. Members of the American Academy of Sleep Medicine developed consensus recommendations for the amount of sleep needed to promote optimal health in children and adolescents using a modified RAND Appropriateness Method. The recommendations are summarized here. A manuscript detailing the conference proceedings and the evidence supporting these recommendations will be published in the Journal of Clinical Sleep Medicine. PMID- 27250810 TI - "Please, sir, I want some more.". PMID- 27250811 TI - Investigating Psychological Mechanisms in Relation to Sleep Problems and Suicide. PMID- 27250812 TI - A Unified Plan to Strengthen the Sleep Medicine Pipeline and Maximize Our Workforce. PMID- 27250813 TI - The Development of Sleep Medicine: A Historical Sketch. AB - ABSTRACT: For centuries the scope of sleep disorders in medical writings was limited to those disturbances which were either perceived by the sleeper him- or herself as troublesome, such as insomnia, or which were recognized by an observer as strange behavioral acts during sleep, such as sleepwalking or sleep terrors. Awareness of other sleep disorders, which are caused by malfunction of a physiological system during sleep, such as sleep-related respiratory disorders, were widely unknown or ignored before sleep monitoring techniques became available, mainly in the second half of the 20(th) century. Finally, circadian sleep-wake disorders were recognized as a group of disturbances by its own only when chronobiology and sleep research began to interact extensively in the last two decades of the 20(th) century. Sleep medicine as a medical specialty with its own diagnostic procedures and therapeutic strategies could be established only when key findings in neurophysiology and basic sleep research allowed a breakthrough in the understanding of the sleeping brain, mainly since the second half of the last century. PMID- 27250814 TI - Mandibular Advancement Device as a Comparable Treatment to Nasal Continuous Positive Airway Pressure for Positional Obstructive Sleep Apnea. AB - STUDY OBJECTIVES: Positional obstructive sleep apnea (P-OSA) is a clinically common phenotype of OSA, which can be treated effectively with mandibular advancement devices (MADs). We hypothesized that the efficacy of an MAD is comparable to that of nasal continuous positive airway pressure (nCPAP) in P-OSA patients. METHODS: Among patients diagnosed with OSA at a single sleep center from January 2008 to May 2014, male subjects with moderate OSA were recruited and stringently categorized as having P-OSA when the ratio of their lateral apnea hypopnea index (AHI) to supine AHI was <= 0.5, their lateral sleep time was > 60 minutes, and their lateral REM sleep time was longer than 10 minutes. Treatment efficacy was compared between P-OSA subjects with an MAD (n = 34) and those with nCPAP (n = 34) after matching for age, body-mass index, and baseline AHI. RESULTS: There were no significant differences in baseline AHI (MAD: nCPAP = 20.6 +/- 3.9/h: 21.3 +/- 1.7/h, p = 0.35) or in follow-up AHI (MAD: nCPAP = 4.7 +/- 3.5/h: 3.4 +/- 3.7/h, p = 0.12) between the 2 treatment groups, and hence MADs lowered the AHI to the same extent as nCPAP. CONCLUSIONS: These findings suggest that an MAD is as efficacious as nCPAP for P-OSA patients. MAD treatment for this specific phenotype may be a promising patient-tailored and first-line approach to OSA. COMMENTARY: A commentary on this article appears in this issue on page 1079. PMID- 27250815 TI - Pain Intensity and Opioid Utilization in Response to CPAP Therapy in Veterans with Obstructive Sleep Apnea on Chronic Opioid Treatment. AB - STUDY OBJECTIVES: Sleep fragmentation has been linked to poor pain tolerance and lowered pain threshold. Little evidence exists on whether continuous positive airway pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA) who are taking opioids for non-malignant pain would ameliorate pain and reduce consumption of opioids. METHODS: A retrospective case-control study was performed at a VA sleep center. Pain intensity was assessed using the Numerical Categorical Scale prior to CPAP treatment and 12-mo follow-up. Opioids intake was assessed using the morphine equivalent daily dose (MEDD). Adherence to CPAP was evaluated with the built-in meter. RESULTS: We reviewed 113 patients with OSA (apnea hypopnea index [AHI] 35.9 +/- 29.5) using a MEDD of 61.6 mg (range 5-980 mg) and a control group of 113 veterans with OSA (AHI 33.4 +/- 27.3) on no opioids treatment. CPAP adherence was significantly lower at 12 mo in opioid-treated patients compared to controls (37% versus 55%; p = 0.01). Greater pain intensity was the only independent variable associated with CPAP non-adherence at 12-mo follow-up (p = 0.03). Compared to baseline, no significant difference was observed in pain intensity or consumption of opioids in CPAP adherent patients. CONCLUSIONS: CPAP treatment did not reduce pain intensity or consumption of opioids in veterans with chronic pain who have coexisting OSA. CPAP adherence was lower in opioid-treated veterans with OSA compared to opioid-free veterans with OSA. Pain intensity was the only determinant of CPAP adherence. Future studies are needed to evaluate pain management program on adherence to CPAP. PMID- 27250816 TI - Sleep Fragmentation Does Not Explain Misperception of Latency or Total Sleep Time. AB - STUDY OBJECTIVES: Perception of sleep-wake times may differ from objective measures, although the mechanisms remain elusive. Quantifying the misperception phenotype involves two operational challenges: defining objective sleep latency and treating sleep latency and total sleep time as independent factors. We evaluated a novel approach to address these challenges and test the hypothesis that sleep fragmentation underlies misperception. METHODS: We performed a retrospective analysis on patients with or without obstructive sleep apnea during overnight diagnostic polysomnography in our laboratory (n = 391; n = 252). We compared subjective and objective sleep-wake durations to characterize misperception. We introduce a new metric, sleep during subjective latency (SDSL), which captures latency misperception without defining objective sleep latency and allows correction for latency misperception when assessing total sleep time (TST) misperception. RESULTS: The stage content of SDSL is related to latency misperception, but in the opposite manner as our hypothesis: those with > 20 minutes of SDSL had less N1%, more N3%, and lower transition frequency. After adjusting for misperceived sleep during subjective sleep latency, TST misperception was greater in those with longer bouts of REM and N2 stages (OSA patients) as well as N3 (non-OSA patients), which also did not support our hypothesis. CONCLUSIONS: Despite the advantages of SDSL as a phenotyping tool to overcome operational issues with quantifying misperception, our results argue against the hypothesis that light or fragmented sleep underlies misperception. Further investigation of sleep physiology utilizing alternative methods than that captured by conventional stages may yield additional mechanistic insights into misperception. COMMENTARY: A commentary on this article appears in this issue on page 1211. PMID- 27250818 TI - Search for aromatic anions in the P2E3(-) (E = N, P, As, Sb, Bi) series. AB - We report a systematic computational study focused on the global minimum and low lying isomer search for the P2E3(-) (E = N, P, As, Sb, Bi) series of anions. We found nine planar five-membered rings and proved their aromatic character by various quantum chemical techniques. The possible use of two different P2N3(-) aromatic anions as ligands in a number of sandwich complexes was also studied. PMID- 27250817 TI - Critical Neural Networks in Awake Surgery for Gliomas. AB - From the embarrassing character commonly infiltrating eloquent brain regions, the surgical resection of glioma remains challenging. Owing to the recent development of in vivo visualization techniques for the human brain, white matter regions can be delineated using diffusion tensor imaging (DTI) as a routine clinical practice in neurosurgery. In confirmation of the results of DTI tractography, a direct electrical stimulation (DES) substantially influences the investigation of cortico-subcortical networks, which can be identified via specific symptoms elicited in the concerned white matter tracts (eg., the arcuate fascicle, superior longitudinal fascicles, inferior fronto-occipital fascicle, inferior longitudinal fascicle, frontal aslant tract, sensori-motor tracts, optic radiation, and so forth). During awake surgery for glioma using DES, it is important to identify the anatomo-functional structure of white matter tracts to identify the surgical boundaries of brain regions not only to achieve maximal resection of the glioma but also to maximally preserve quality of life. However, the risk exists that neurosurgeons may be misled by the inability of DTI to visualize the actual anatomy of the white matter fibers, resulting in inappropriate decisions regarding surgical boundaries. This review article provides information of the critical neuronal network that is necessary to identify and understand in awake surgery for glioma, with special references to white matter tracts and the author's experiences. PMID- 27250819 TI - New approach to treating spinal cord injury using PEG-TAT-modified, cyclosporine A-loaded PLGA/polymeric liposomes. AB - Cyclosporine-A (CsA) is an immunosuppressant agent that has shown effectiveness as a neuroprotective drug; however, it does not readily cross the blood-spinal cord barrier (BSCB), which constrains the clinical applications of CsA for the treatment of spinal cord injury (SCI). Our group recently tested the ability of novel polyethylene glycol (PEG)-transactivating-transduction protein (TAT) modified CsA-loaded cationic multifunctional polymeric liposome-poly(lactic-co glycolic acid) (PLGA) core/shell nanoparticles (PLGA/CsA NPs) to transport and deliver CsA across the BSCB to treat SCI. The PLGA/CsA NPs were successfully constructed. In vitro drug release studies have demonstrated that the sustained release of CsA from PLGA/CsA NPs occurs over ~25 h. The in vivo study presented here showed that injured animals that received PLGA/CsA NPs through the tail vein, exhibited a significant up-regulation of growth-associated protein-43 (GAP 43) expression and an increased number of GAP-43-stained neurons compared with animals that received CsA or the vehicle alone. The improvement in neurological function was also evaluated by the Basso-Beattie-Bresnahan (BBB) open-field test. Moreover, fluorescein isothiocyanate (FITC)-attached PLGA/CsA NPs were successfully aggregated in the intact spinal cord 4 h after injection. Our data suggest that PLGA/CsA NPs have the potential for use as a new treatment method for SCI. PMID- 27250820 TI - Role of freeze-thaw cycles and chlorpyrifos insecticide use on diffuse Cd loss and sediment accumulation. AB - Freeze-thaw cycles are predicted to increase in cold temperate regions. The potential influence of the interactions of freeze-thaw cycles and agrochemicals on the release of Cd into river water is unknown. In this study, the interactions of freeze-thaw cycles and chlorpyrifos (FC) on Cd mobility in soils were analysed. The spatial variability of soil Cd under long-term intensive tillage in a freeze-thaw agro-system was also identified. The temporal variation of sediment Cd was detected based on analysis of the sediment geochemistry. The results showed that FC increased soil Cd mobility, with an increase of approximately 10% in CaCl2-extractable Cd. The increased mobile fractions of water-soluble and exchangeable Cd originated from the decreased fraction of Fe-Mn-oxide-associated Cd and organic matter-bound Cd. The total Cd content in the surface soil followed the zonally decreasing trend of dry land > paddy land > natural land. The Cd concentrations and sedimentation rates of the sediment core generally increased from 1943 to 2013 due to agricultural exploration and farmland irrigation system construction, indicating an increase of the Cd input flux into water. The results provide valuable information about the soil Cd transport response to the influence of climatic and anthropogenic factors in cold intensive agro-systems. PMID- 27250821 TI - Syndromes with supernumerary teeth. AB - While most supernumerary teeth are idiopathic, they can be associated with a number of Mendelian syndromes. However, this can also be a coincidental finding, since supernumerary teeth occur in 6% or more of the normal population. To better define this relationship, we analyzed the evidence for specific associations. We excluded conditions with a single affected patient reported, supernumerary teeth adjacent to clefts or other forms of alveolar disruption (as secondary rather than primary findings), and natal teeth, which can involve premature eruption of a normal tooth. Since, the cause of supernumerary teeth shows considerable heterogeneity, certain findings are less likely to be coincidental, such as five or more supernumerary teeth in a single patient, or locations outside of the premaxilla. We found only eight genetic syndromes with strong evidence for an association: cleidocranial dysplasia; familial adenomatous polyposis; trichorhinophalangeal syndrome, type I; Rubinstein-Taybi syndrome; Nance-Horan syndrome; Opitz BBB/G syndrome; oculofaciocardiodental syndrome; and autosomal dominant Robinow syndrome. There is also suggestive evidence of an association with two uncommon disorders, Kreiborg-Pakistani syndrome (craniosynostosis and dental anomalies), and insulin-resistant diabetes mellitus with acanthosisnigricans. An association of a Mendelian disorder with a low frequency manifestation of supernumerary teeth is difficult to exclude without large numbers, but several commonly cited syndromes lacked evidence for clear association, including Hallermann-Streiff syndrome, Fabry disease, Ehlers-Danlos syndrome, Apert and Crouzon syndromes, Zimmermann-Laband syndrome, and Ellis-van Creveld syndrome. (c) 2016 Wiley Periodicals, Inc. PMID- 27250822 TI - Spherical cap surface model: A novel method for predicting renal function after partial nephrectomy. AB - OBJECTIVES: To estimate the percent functional volume preservation from preoperative images using a novel method, the spherical cap surface model, and to investigate whether this model can preoperatively predict renal function after partial nephrectomy. METHODS: A total of 233 patients with renal cell carcinoma who underwent open or laparoscopic partial nephrectomy between January 2011 and December 2013 were included in the present study. The spherical cap surface model was used to calculate the estimated percent functional volume preservation on preoperative computed tomography, and the estimated percent functional volume preservation was multiplied by the preoperative estimated glomerular filtration rate to predict the postoperative estimated glomerular filtration rate. The occurrence of acute kidney injury also served as an outcome. Univariate and multivariate linear regression, and receiver operating characteristic curve analysis were used to test the model. RESULTS: The estimated percent functional volume preservation calculated by the novel model was significantly associated with both nadir percent estimated glomerular filtration rate preservation and late percent estimated glomerular filtration rate preservation in the multivariate analysis (the P-values were 0.021 and 0.043, respectively). Receiver operating characteristic curve analysis for predicting acute kidney injury after partial nephrectomy showed that volume preservation (P < 0.001) and warm ischemia time (P = 0.040) were both significant. Regarding the ability to predict a significant decrease in late renal function after partial nephrectomy, only volume preservation (P = 0.044) was significant. CONCLUSIONS: Preservation of functional volume is the primary determinant of functional outcomes after partial nephrectomy. The spherical cap surface model seems to represent a promising tool to predict nadir and late postoperative renal function in patients undergoing partial nephrectomy. PMID- 27250823 TI - Diagnostic utility of additional conventional techniques after endobronchial ultrasonography guidance during transbronchial biopsy. AB - BACKGROUND AND OBJECTIVE: Endobronchial ultrasonography with a guide sheath transbronchial biopsy (EBUS-GS TBB) has been used to diagnose peripheral pulmonary lesions (PPLs). In this study, we evaluated the diagnostic utility of conventional TBB after EBUS-GS TBB. METHODS: A retrospective analysis of patients who underwent conventional TBB after EBUS-GS TBB for PPL between August 1, 2012 and December 31, 2014. We performed multivariate analysis to examine the association of various clinical factors, including EBUS probe distance and sample size area, with diagnostic yield. RESULTS: Of 88 eligible patients, 57 (65%) were successfully diagnosed by EBUS-GS TBB. In 31 patients not diagnosed by EBUS-GS TBB, 15 (48%) were successfully diagnosed by additional conventional TBB. Ground glass opacity (GGO) was a significant factor associated with the diagnostic yield of additional conventional TBB following EBUS-GS TBB. Multivariate analysis and receiver operator curves revealed that distance between the PPL and the EBUS probe of less than 2.55 mm favored the utility of conventional TBB. CONCLUSION: Additional conventional TBB after EBUS-GS TBB could be a useful procedure for the diagnosis of ground glass opacity PPLs and in cases of a distance of less than 2.55 mm between the EBUS probe and the lesion. PMID- 27250824 TI - Hb San Cataldo [beta144(HC1)Lys->Thr; HBB: C.434A > C]: A New Hemoglobin Variant with Increased Affinity for Oxygen. AB - A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire beta-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the beta-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys->Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C terminal of the beta chain. We called this new variant Hb San Cataldo for the native city of proband. PMID- 27250826 TI - Familial Mediterranean fever complicated with refractory asthma: Successful treatment with colchicine. PMID- 27250827 TI - Role of hepcidin and its downstream proteins in early brain injury after experimental subarachnoid hemorrhage in rats. AB - Early brain injury (EBI) is a major cause of mortality from subarachnoid hemorrhage (SAH). We aimed to study the pathophysiology of EBI and explore the role of hepcidin, a protein involved in iron homeostatic regulation, and its downstream proteins. One hundred and thirty-two male Sprague-Dawley rats were assigned into groups (n = 24/group): sham, SAH, SAH + hepcidin, SAH + hepcidin targeting small interfering ribonucleic acid (siRNA), and SAH + scramble siRNA. Three hepcidin-targeting siRNAs and one scramble siRNA for hepcidin were injected 24 h before hemorrhage induction, and hepcidin protein was injected 30 min before induction. The rats were neurologically evaluated at 24 h and euthanized at 72 h. Hepcidin, ferroportin-1, and ceruloplasmin protein expression were measured by immunohistochemistry and Western blotting. Brain water content, blood-brain barrier (BBB) leakage, non-heme tissue iron and Garcia scale were evaluated. Hepcidin expression increased in the cerebral cortex and hippocampus after experimental SAH (P < 0.05 compared to sham), while ferroportin-1 and ceruloplasmin decreased (P < 0.05). Hepcidin injection lowered the expression of ferroportin-1 and ceruloplasmin further but siRNA reduced the levels of hepcidin (P < 0.05 compared to SAH) resulting in recovery of ferroportin-1 and ceruloplasmin levels. Apoptosis was increased in SAH rats compared to sham (P < 0.05) and increased slightly more by hepcidin, but decreased by siRNA (P < 0.05 compared to SAH). SAH rats had lower neurological scores, high brain water content, BBB permeability, and non-heme tissue iron (P < 0.05). In conclusion, downregulation of ferroportin-1 and ceruloplasmin caused by hepcidin enhanced iron-dependent oxidative damage and may be the potential mechanism of SAH. PMID- 27250825 TI - Anti-fibrotic actions of relaxin. AB - : Fibrosis refers to the hardening or scarring of tissues that usually results from aberrant wound healing in response to organ injury, and its manifestations in various organs have collectively been estimated to contribute to around 45-50% of deaths in the Western world. Despite this, there is currently no effective cure for the tissue structural and functional damage induced by fibrosis-related disorders. Relaxin meets several criteria of an effective anti-fibrotic based on its specific ability to inhibit pro-fibrotic cytokine and/or growth factor mediated, but not normal/unstimulated, fibroblast proliferation, differentiation and matrix production. Furthermore, relaxin augments matrix degradation through its ability to up-regulate the release and activation of various matrix-degrading matrix metalloproteinases and/or being able to down-regulate tissue inhibitor of metalloproteinase activity. Relaxin can also indirectly suppress fibrosis through its other well-known (anti-inflammatory, antioxidant, anti-hypertrophic, anti apoptotic, angiogenic, wound healing and vasodilator) properties. This review will outline the organ-specific and general anti-fibrotic significance of exogenously administered relaxin and its mechanisms of action that have been documented in various non-reproductive organs such as the cardiovascular system, kidney, lung, liver, skin and tendons. In addition, it will outline the influence of sex on relaxin's anti-fibrotic actions, highlighting its potential as an emerging anti-fibrotic therapeutic. LINKED ARTICLES: This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc. PMID- 27250828 TI - Anatomical and functional changes to the pelvic floor after robotic versus laparoscopic ventral rectopexy: a randomised study. AB - INTRODUCTION AND HYPOTHESIS: To compare the effect of laparoscopic and robot assisted ventral rectopexy for posterior compartment procidentia on the pelvic floor anatomy and function. METHODS: A prospective randomised single-centre study was carried out of 29 female patients, who underwent robot-assisted or laparoscopic ventral mesh rectopexy for external or internal rectal prolapse with symptoms of obstructive defecation and/or faecal incontinence. Anatomical changes were measured by Pelvic Organ Prolapse Quantification (POP-Q) and magnetic resonance defecography. Functional changes were evaluated using symptom questionnaires before and 3 months after surgery. RESULTS: After rectopexy, changes in POP-Q measurements were statistically significant for points Ap, Bp, C, D and Ba. The descent of the anorectum and cervix/vaginal cuff during straining were significantly reduced with regard to the reference line (mean, 10.4 +/- 14.9 mm, p = 0.001) and (-13.3 +/- 18.1 mm, p < 0.001) respectively. Pelvic organ mobility (POM) was reduced statistically significantly for the posterior (mean, -16.6 +/- 20.8 mm, p < 0.001) and apical compartments (mean, 13.1 +/- 14.8, p < 0.001). The PFDI-20, PFIQ-7 and PISQ-12 questionnaires showed statistically significant improvement of symptoms and sexual function. No significant differences were observed between the robot-assisted and laparoscopic techniques in terms of anatomical or functional parameters. CONCLUSION: Ventral mesh recto-colpo-sacropexy effectively corrects the anatomy of the posterior compartment, elevates the vaginal apex and reduces pelvic organ mobility of the posterior and middle compartments. The robot-assisted and laparoscopic techniques had similar anatomical and functional outcomes. PMID- 27250829 TI - Laparoscopic wrap round mesh sacrohysteropexy for the management of apical prolapse. AB - INTRODUCTION AND HYPOTHESIS: Interest in uterine-conserving surgery for apical prolapse is growing. Laparoscopic sacrohysteropexy is one of the conservative surgical options, although different surgical approaches have been described. We report medium-term outcome data using a bifurcated mesh implant, employing 'wrap round' uterine attachment. METHODS: All procedures undertaken at our unit were reviewed. Study inclusion was contingent on the collection of baseline and 3 month anatomical and symptomatic outcome data. Medium-term follow-up data were collected by telephone review. Anatomical outcome was reported using the Pelvic Organ Prolapse Quantification scale. Symptom prevalence and treatment response were assessed using validated instruments including the Patient Global Impression of Improvement scale (PGI-I), and the International Consultation on Incontinence Urinary Incontinence Short Form (ICIQ-UI) and Vaginal Symptoms (ICIQ-VS) questionnaires. Patient satisfaction was reported using Kaplan-Meier survival analysis. RESULTS: Data were available for 110 patients. Of 80 patients providing PGI-I data at 3 months, 75 (94 %) described their prolapse symptoms as 'much better' or 'very much better'. Anatomical success in the apical compartment was 98 %. ICIQ-UI and ICIQ-VS responses demonstrated significant improvement. Despite a concurrent vaginal repair in only 11 % of patients, satisfaction at a mean follow-up of 2.6 years was 96 %. Repeat surgery for vaginal wall prolapse was required in only 5 % of patients. No safety concerns or graft complications were recorded. CONCLUSIONS: This surgical variant of laparoscopic sacrohysteropexy is safe and highly effective. These data also cast doubt on the need for correction of modest vaginal wall prolapse at the time of surgery, and imply that apical prolapse may play a dominant role in the generation of symptoms. PMID- 27250830 TI - Fulfilment of patient goals after tension-free vaginal tape operation for stress urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to investigate patient reported goals after a tension-free vaginal tape operation for stress urinary incontinence and the correlation with postoperative incontinence. METHODS: A prospective study involving 70 women was carried out. Preoperatively, patients completed the International Consultation on Incontinence Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF) and stated three goals for the operation. A telephone interview was performed 3 months postoperatively. RESULTS: A Visual Analogue Scale (VAS) score from zero to ten estimated the extent to which goals were achieved. Goals were divided into five groups: 1, symptoms; 2, quality of life (physical); 3, quality of life (emotional); 4, sexual function; 5, avoidance. ICIQ-UI SF preoperative mean was 14.9 and postoperative mean was 1.5 (p < 0.05). A total of 210 goals were stated. The majority of the goals (38 %) were in group 2 concerning quality of life in the physical domains. Mean VAS score for all goals was 9.1 (SD 2). Thirty-seven patients (53 %) fulfilled all their goals. Twenty-one patients (30 %) did not have a VAS score of 10, although continent with an ICIQ-UI SF score of zero. Reasons for not achieving a full VAS score were that some still used pads out of fear (n = 10), that their mental focus was still on incontinence (n = 7) or that they had not yet tried some of the physical aims (n = 7). CONCLUSIONS: Most patients achieved their goals. The majority of the goals concerned quality of life in the physical domains. PMID- 27250831 TI - Effectiveness of adding voluntary pelvic floor muscle contraction to a Pilates exercise program: an assessor-masked randomized controlled trial. AB - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to evaluate the effectiveness of adding voluntary pelvic floor muscle contraction (PFMC) to a Pilates exercise program in sedentary nulliparous women. METHODS: Fifty-seven healthy nulliparous and physically inactive women were randomized to a Pilates exercise program (PEP) with or without PFMC. Forty-eight women concluded this study (24 participants for each group). Each woman was evaluated before and after the PEP, by a physiotherapist and an urogynecologist (UG). Neither of the professionals was revealed to them. This physiotherapist measured their pelvic floor muscle strength by using both a perineometer (Peritron) and vaginal palpation (Oxford Scale). The UG, who performed 3D perineal ultrasound examinations, collected their data and evaluated the results for pubovisceral muscle thickness and the levator hiatus area (LA). Both professionals were blinded to the group allocation. The protocol for both groups consisted of 24 bi weekly 1-h individual sessions of Pilates exercises, developed by another physiotherapist who specializes in PFM rehabilitation and the Pilates technique. RESULTS: The PEP+ PFMC group showed significantly greater strength improvements than the PEP group when comparing the Oxford scale, vaginal pressure and pubovisceral muscle thickness during contraction measurements at baseline and post-treatment. CONCLUSIONS: Our findings suggest that adding a voluntary PFMC to a Pilates exercise program is more effective than Pilates alone in improving PFM strength in sedentary nulliparous women. PMID- 27250832 TI - The evolution of transperineal ultrasound findings of the external anal sphincter during the first years after childbirth. AB - INTRODUCTION AND HYPOTHESIS: Obstetric anal sphincter injuries (OASI) are a major form of maternal birth trauma. Ultrasound imaging is commonly used to evaluate the condition. We undertook a study to compare the sonographic appearance of the external anal sphincter (EAS) 3 to 6 months and 2 to 3 years after a first birth. METHODS: A retrospective analysis of data of primiparous women obtained in a prospective perinatal imaging study. Women were invited for postnatal assessment 3 - 6 months and 2 - 3 years after a first delivery. All had completed a standardized questionnaire, and had undergone clinical examination and translabial 4D ultrasound imaging. A "significant" EAS defect was diagnosed if four out of six slices on tomographic ultrasound imaging showed a defect of >=30 degrees circumference. RESULTS: Datasets of 76 women with complete data and no intervening birth were assessed. Their mean age was 30.0 years (range 19.5 - 45.3 years) at the time of antenatal assessment. They were delivered at a mean gestation of 40 weeks (range 37 - 42 weeks), by caesarean section in 19, normal vaginal delivery in 42, vacuum delivery in 14 and forceps delivery in 1. A significant EAS defect on transperineal ultrasound imaging was found in 13 of 57 women (23 %) at an average of 4.7 months and in 12 of 57 (21 %) at a mean 26.4 months after a first vaginal delivery. CONCLUSIONS: In this cohort of primiparous women after a term singleton delivery, we found only minor improvement in sonographic appearance of the EAS between 4.7 months and 26.4 months on transperineal ultrasound imaging, arguing against any significant degree of structural recovery during this time period. PMID- 27250833 TI - Quality of life outcomes in peri-urethral calcium hydroxylapatite injection. AB - INTRODUCTION AND HYPOTHESIS: Peri-urethral calcium hydroxylapatite injection is an established treatment for patients with stress urinary incontinence. Information is limited regarding calcium hydroxylapatite treatment and quality of life (QOL) outcomes. We hypothesize that patients might improve QOL after peri urethral calcium hydroxylapatite injection, which was reflected in validated questionnaires. METHODS: The peri-urethral calcium hydroxylapatite injection billing code was used to identify patients who underwent injection from 2011 2013. Female patients who completed the American Urological Association Symptom Score (AUASS), the AUASS QOL and Michigan Incontinence Symptom Index (M-ISI), and the bother score (M-ISI bother), or pad count at baseline and follow-up were included. Change in questionnaire scores and pads were assessed using the paired t test. RESULTS: Sixty patients underwent 1 (30), 2 (63) or 3 (7 %) peri-urethral calcium hydroxylapatite injections performed by a single surgeon. Thirty-seven patients provided questionnaires and 38 provided pad counts, all with a mean age of 75 years. The overall AUASS, AUASS QOL, and overall M-ISI scores improved in 67.6, 54.8, and 61.3 % respectively (4.5 +/- 7.9, 1.3 +/- 1.7 and 5.5 +/- 8.6 respectively). The M-ISI bother score improved in 44.8 % with a mean improvement of 0.5 +/- 2.9, but did not reach significance. There was a 1.7 +/- 3.7 decrease in the mean number of pads used daily after the procedure (p = 0.006) and 19 % experienced transient urinary retention. CONCLUSIONS: Peri-urethral calcium hydroxylapatite injections can improve urinary QOL scores in patients with initial and recurrent stress urinary incontinence. This short-term retrospective analysis suggests that larger long-term studies focusing on QOL outcomes are needed to evaluate the effect of peri-urethral calcium hydroxylapatite has on incontinence-specific QOL. PMID- 27250834 TI - Assessing the use of the IUGA/ICS classification system for prosthesis/graft complications in publications from 2011 to 2015. AB - INTRODUCTION AND HYPOTHESIS: Complications of pelvic organ prolapse and urinary incontinence surgery have gained increasing attention from both lay media and medical societies. The International Urogynecological Association and International Continence Society proposed the category-time-site system to classify complications in 2011. Our objective is to assess the usage of the category-time-site system in the literature. METHODS: We conducted a systematic review and identified records using PubMed search terms "mesh" and "prolapse or incontinence" and "complication or excision" (February 2011 to December 2015) to select publications following the introduction of category-time-site system. Relevant publications were included and reviewed for study design, initial procedure, number of patients assigned codes, number of unique codes applied, purpose of assigning codes, and duration of clinical follow-up. RESULTS: Of 167 eligible records, 23 (14 %) used the system, 137 (82 %) used no system, and 7 (4 %) used another system. They included three study designs: randomized control trials, case reports, and case series. Given the very limited amount of data, no statistical tests were performed, but trends were noted. CONCLUSIONS: Fourteen percent of the reports in the literature describing complications related to prosthesis/graft use in pelvic surgery utilize the category-time-site system. The system's limited and inconsistent use hinders the ability to draw conclusions useful for clinical practice. Effort should be directed toward improving appropriate usage or revising the system to increase its exposure in related publications. An improved system will better prepare pelvic surgeons for assessing future generations of prostheses/grafts. PMID- 27250835 TI - Long-term monitoring of opioid, sedative and anti-inflammatory drugs in horse hair using a selective and sensitive LC-MS/MS procedure. AB - BACKGROUND: Compared to blood or urine, drugs can be detected for much longer periods in the long hair of horses. The aim of this study was to establish and validate a highly sensitive liquid chromatography tandem mass spectrometry (LC MS/MS) method for the detection and quantification of frequently prescribed opioids, sedatives and non-steroidal anti-inflammatory agents in the mane and tail hair of horses. Based on an average growth rate of about 2 cm per month, times of administration reported by horse owners or veterinary physicians were related to drug localizations in hair. Hair samples were collected from ten horses that received drug treatments and analyzed in segments of 2, 4 or 6 cm in length. Hair segments were decontaminated, cut into fragments and methanol extracted under sonication. The extracts were analyzed by LC-MS/MS for 13 commonly used drugs using the validated procedure. Deuterated analogs were included as internal standards. RESULTS: Analytes were detected in hair samples with a length of up to 70 cm. Fourteen out of 16 hair samples were positive for at least one of the tested drugs. Segmentation allowed for time-resolved monitoring of periods of 1 to 3 months of drug administration. Concentrations in dark hair reached a maximum of 4.0 pg/mg for butorphanol, 6.0 pg/mg for tramadol, 1.4 pg/mg for morphine, 1.8 pg/mg for detomidine, 1.2 pg/mg for acepromazine, 39 pg/mg for flunixin, 5.0 pg/mg for firocoxib, and 3'600 pg/mg for phenylbutazone. Only trace amounts of meloxicam were detected. Drug detection correlated well with the reported period of medical treatment. No analytes were detected in the light-colored mane and tail hair samples from one horse despite preceding administrations of acepromazine and phenylbutazone. CONCLUSION: This study describes a sensitive and selective technique suitable for the validated detection and quantification of frequently prescribed veterinary drugs in horse hair. The segmental method can be applied for time-resolved long-term retrospective drug monitoring, for example in prepurchase examinations of horses as drug detection in hair can prove preceding medical treatments. PMID- 27250837 TI - Screening for BPPV in falls: an easy but big clinical "win". PMID- 27250836 TI - Reduction of cytosolic phospholipase A2alpha upregulation delays the onset of symptoms in SOD1G93A mouse model of amyotrophic lateral sclerosis. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal multifactorial neurodegenerative disease characterized by selective death of motor neurons in the cortex, brainstem, and spinal cord. Cytosolic phospholipase A2 alpha (cPLA2alpha) upregulation and activation in the spinal cord of patients with sporadic ALS and in the spinal cord of human mutant SOD1G93A (hmSOD1) transgenic mice were recently reported. METHODS: cPLA2alpha upregulation in the brainstem and spinal cord was reduced by brain infusion of a specific antisense oligonucleotide against cPLA2alpha (AS), and the effect was evaluated on disease progression and brain cell activation. RESULTS: We found that the elevation of cPLA2alpha protein expression in the spinal cord was first detected at 6-week-old hmSOD1 mice and remained elevated during their whole life span. Reduction of the elevated expression of cPLA2alpha in the spinal cord of hmSOD1 mice by brain infusion of an AS at week 15 (shortly before the appearance of the disease symptoms), for a duration of 6 weeks, delayed the loss of motor neuron function in comparison with hmSOD1 mice and with sense brain-infused hmSOD1 mice. To characterize the effect of cPLA2alpha upregulation on different processes taking place at the appearance of the disease symptoms, mice were brain infused with AS or with sense at week 15 for 3-4 weeks. The AS treatment that reduced cPLA2alpha upregulation in the spinal cord of AS-treated hmSOD1 mice (as analyzed at week 18 19) prevented the reduction in the number of the neurons (detected by NeuN) and inhibited astrocyte activation (detected by GFAP) and microglia activation (detected by Iba-1 and by CD40). In addition, AS treatment blunted the upregulation of the proinflammatory enzyme-inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) detected in hmSOD1 mice. CONCLUSIONS: Since specific reduction of cPLA2alpha in the brainstem and spinal cord significantly attenuated the development of the disease, cPLA2alpha may offer an efficient target for treatment of ALS. PMID- 27250838 TI - Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression. AB - BACKGROUND: We investigated whether GKN1, a gastric tumor suppressor, contributes to the progression of gastric cancer by regulating RhoA expression. METHODS: We analyzed the expression of GKN1, RhoA, miR-185, and miR-34a in 35 gastric cancer tissues, and compared their expression with T category and TNM stage. Cell migration and invasion, as well as the expression of epithelial-to-mesenchymal transition (EMT)-related proteins, were assessed in GKN1- and RhoA small interfering RNA (siRhoA)-transfected and recombinant-GKN1-treated AGS and MKN1 gastric cancer cells. RESULTS: Expression of RhoA protein and messenger RNA (mRNA) was increased in 15 (42.9 %) and 17 (48.6 %) of 35 gastric cancer tissues respectively, and was associated with higher T category and TNM stage. GKN1 expression was significantly decreased in 27 gastric cancers (77.1 %) with a higher T category, and was inversely correlated with RhoA mRNA expression. In AGS and MKN1 cells, GKN1 expression increased miR-185 and miR-34a expression and reduced RhoA mRNA and protein expression. A positive relationship between GKN1 and miR-34a and miR-185 expression and an inverse relationship between miR-34a and RhoA expression were observed in gastric cancer tissues. Cell migration and invasiveness were markedly decreased in GKN1- and siRhoA-transfected cells. GKN1 expression and silencing of RhoA decreased the expression of the proteins Snail, Slug, and vimentin. Furthermore, miR-185 and miR-34a silencing in MKN1 cells transfected with GKN1 stimulated cell migration and invasion, and increased the expression of EMT-related proteins. CONCLUSION: Our data suggest that GKN1 may inhibit gastric cancer cell migration and invasion by downregulating RhoA expression in a miR-185- and miR-34a-dependent manner. PMID- 27250840 TI - Anticancer effects of synthetic hexahydrobenzo [g]chromen-4-one derivatives on human breast cancer cell lines. AB - BACKGROUND: Cancer results from a series of molecular changes that alter the normal function of cells. Breast cancer is the second leading cause of cancer death in women. To develop novel anticancer agents, new series of chromen derivatives were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines. METHOD: The growth inhibitory activities of synthesized hexahydrobenzo chromen-4-one were screened against six human cancer cell lines using an in vitro cell culture system (MTT assay). Fluorochrome staining (acridine orange/ethidium bromide double staining) and DNA fragmentation by the diphenylamine method were used to investigate the effects of most potent compounds on the process of apoptosis in breast cancer cell lines. To determine the mechanism of apoptosis, ROS and NOX production in treated breast cancer cells with compounds was evaluated. RESULTS: The cytotoxicity data of tested compounds demonstrate these compounds had varying degree of toxicity. Compound 7h was the most potent compound with IC50 = 1.8 +/- 0.6 ug/mL against T-47D cell line. Analyses of the compounds treated (MCF-7, MDA-MB-231, and T-47D) cells by acridine orange/ethidium bromide double staining and DNA fragmentation by the diphenylamine method showed that the synthetic compounds induce apoptosis in the cells. A significant increase in ROS production was observed in T-47D cells treated with IC50 value of compound 7g. Incubation with IC50 value of synthetic compounds increased the NOX production in cell lines, especially T-47D cells. CONCLUSION: Our results show that most compounds have a significant anti proliferative activity against six human cancer cell lines. The observations confirm that chromen derivatives have induced the cell death through apoptosis. PMID- 27250839 TI - Acute and Chronic Cutaneous Reactions to Ionizing Radiation Therapy. AB - Ionizing radiation is an important treatment modality for a variety of malignant conditions. However, development of radiation-induced skin changes is a significant adverse effect of radiation therapy (RT). Cutaneous repercussions of RT vary considerably in severity, course, and prognosis. When they do occur, cutaneous changes to RT are commonly graded as acute, consequential-late, or chronic. Acute reactions can have severe sequelae that impact quality of life as well as cancer treatment. Thus, dermatologists should be informed about these adverse reactions, know how to assess their severity and be able to determine course of management. The majority of measures currently available to prevent these acute reactions are proper skin hygiene and topical steroids, which limit the severity and decrease symptoms. Once acute cutaneous reactions develop, they are treated according to their severity. Treatments are similar to those used in prevention, but incorporate wound care management that maintains a moist environment to hasten recovery. Chronic changes are a unique subset of adverse reactions to RT that may develop months to years following treatment. Chronic radiation dermatitis is often permanent, progressive, and potentially irreversible with substantial impact on quality of life. Here, we also review the etiology, clinical manifestations, pathogenesis, prevention, and management of late-stage cutaneous reactions to radiotherapy, including chronic radiation dermatitis and radiation-induced fibrosis. PMID- 27250841 TI - Predisposing factors for adverse skin reactions with percutaneous bone anchored hearing devices implanted with skin reduction techniques. AB - We present an analysis of adverse events after implantation of bone anchored hearing device in our patient population with focus on individual risk factors for peri-implant skin reactions. The investigation involved a chart review of adult Baha patients (n = 179) with 203 Bahas implanted with skin reduction techniques between 1993 and 2009, a questionnaire (n = 97) and a free clinical examination (n = 47). Skin reactions were graded by severity from 0 (no skin reaction) to 4 (implant loss resulting from infection) according to Holgers. We analyzed the skin reaction rate (SRR) defined as the number of skin reactions per year and the worst Holgers grade (WHG), which indicates the grade of the worst skin reaction per implant. We defined 20 parameters including the demographic characteristics, surgery details, subjective benefits, handling and individual factors. The most frequent adverse events (85 %) were skin reactions. The average SRR was 0.426 per Baha year. Six parameters showed an association with the SRR or the WHG. The clinically most relevant factors are an elevated Body Mass Index (BMI, p = 0.02) and darker skin type (p = 0.03). The SRR increased with the distance between the tragus and the implant (p = 0.02). Regarding the identified risk factors, the SRR might be reduced by selecting a location for the implant near the pinna and by specific counseling regarding post-operative care for patients with darker skin type or an elevated Body Mass Index (BMI). Few of the factors analyzed were found to influence the SRR and WHG. Since most adverse skin reactions could be treated easily with local therapy, our results suggest that in adult patients, individual risk factors for skin reactions are not a contraindication for Baha implantation. Thus, patients can be selected purely on audiological criteria. PMID- 27250842 TI - Decreasing the Stigma of Mental Illness Through a Student-Nurse Mentoring Program: A Qualitative Study. AB - Stigma is defined as endorsing prejudicial attitudes about mental illness leading to discriminatory behaviors. It undermines the quality of medical care received by people with mental illness. Research suggests contact based interventions are effective in reducing stigma and increasing positive attitudes towards people with mental illness. This paper describes the development of a consumer led student-nurse mentoring program as part of nursing student education. People with lived mental health experience would mentor student nurses regarding the harmful effects of stigma and the beneficial outcomes of affirming attitudes. Seventy members of stakeholder groups (people with lived mental health experience and student nurses) participated in focus groups. Qualitative analyses revealed themes across stakeholder groups regarding: perceived mental health stigma from nurses, ways to reduce stigma, target message for the mentorship program, characteristics of mentors and logistics in developing such a program within the student nurse curricula. PMID- 27250843 TI - Effective Prevention Strategies for Increasing Health Services Utilization Among Hispanic Youth. AB - The study purpose is to address the underutilization of mental health services among Hispanic youth. This article provides professionals with strategies to increase health services utilization by utilizing a framework of the levels of prevention model, with an emphasis on primary prevention. The following questions were explored: (1) What are primary prevention strategies that can assist school professionals? (2) What are secondary prevention strategies and tertiary prevention strategies school professionals can employ to increase the utilization of health services? Implementing primary, secondary, and tertiary prevention strategies may improve Hispanic youth's overall mental health, academic achievement, and quality of life. PMID- 27250844 TI - Behavioral Health Problems Presented to Integrated Pediatric Behavioral Health Clinics: Differences in Urban and Rural Patients. AB - Behavioral health diagnoses and service use may differ based on rurality. The purpose of this study was to examine the patterns of mental disorder diagnoses of urban, rural, and remote pediatric populations. This retrospective study used electronic medical records from integrated behavioral health clinics in Nebraska from 2012 to 2013. Bivariate and multivariable models were used to examine the differences in diagnoses. Adolescents with attention deficit and related disorders were more likely to be male, younger, have public insurance and rural/remote residents. Adjustment disorders were associated with being female, older, and urban residents. Adolescents with anxiety disorder had a significant interaction between age and gender, with both genders being older, having private insurance, and urban residents. Adolescents with mood disorder were more likely to be female, older, and urban residents. Demographic and clinical differences among patients in urban and rural/remote settings have implications for care in rural settings. PMID- 27250845 TI - Evidence for safety of retreatment with a single intra-articular injection of Gel 200 for treatment of osteoarthritis of the knee from the double-blind pivotal and open-label retreatment clinical trials. AB - BACKGROUND: Gel-200 is a cross-linked hyaluronate single-injection device for treatment of osteoarthritis pain in the knee. This report summarizes new analyses of the safety of retreatment with Gel-200 from the 13-week, pivotal, multicenter, randomized controlled trial (RCT) followed by an open-label extension trial (OLE). METHODS: 379 patients were enrolled in the RCT [Gel-200; phosphate buffered saline (PBS)]. Safety of retreatment with Gel-200 was assessed by comparing adverse events (AEs) and device-related AEs reported through Week 4 following retreatment with Gel-200 to those reported in patients receiving their first injection in the OLE. RESULTS: 350 patients completed the initial RCT (231 Gel-200; 119 PBS); 258 patients enrolled in the OLE (162 Gel-200; 96 PBS). In total, 202 patients (125 Gel-200; 77 PBS) qualified for retreatment, while 56 (37 Gel-200; 19 PBS) did not. There were no significant demographic or disease characteristic differences between Gel-200 patients who were and were not retreated; those who were not eligible for retreatment experienced greater pain relief from Gel-200 in the RCT by all effectiveness endpoints (all p < 0.001), without differences in their safety profile. In the OLE, the safety of Gel-200, including percentages of patients who experienced any AEs (p = 0.547) and device related AEs (p = 0.521), did not significantly differ between those receiving a second versus a first injection of Gel-200 following PBS in the RCT. CONCLUSION: In the OLE, the safety of a second injection of Gel-200 was comparable to that of a first injection and effectiveness was similar, as previously reported. TRIAL REGISTRATION: ClinicalTrials.gov identification numbers NTC 00449696 and NTC 00450112. PMID- 27250846 TI - Is a Central Venous Catheter Necessary for the Perioperative Management of Esophagectomy? A Prospective Randomized Pilot Study Comparing Two Different Perioperative Regimens. AB - BACKGROUND/AIMS: Our prospective randomized study examined the possibility of perioperative management of esophagectomy without a central venous catheter (CVC). METHODS: Forty patients who underwent esophagectomy for esophageal cancer were divided into the total parenteral nutrition (TPN; receiving conventional perioperative management via a CVC) and peripheral parenteral nutrition (PPN; receiving perioperative management without a CVC) groups. Albumin and retinol binding protein (RBP) levels were used as measurements of the nutritional status. Early postoperative complications and catheter-related complications were also evaluated. RESULTS: The actual calories administered per kg of body weight and the albumin and RBP levels did not significantly differ between the groups. Additionally, there was no significant difference in the morbidity of early postoperative complications between the groups. Catheter-related complications were observed in 4 patients in the TPN group (2 catheter infections, 1 case of thrombosis, and 1 case of iatrogenic pneumothorax), and 4 cases of peripheral phlebitis occurred in the PPN group. The incidence of catheter-related complications did not significantly differ between the groups. CONCLUSIONS: Perioperative management without a CVC can be safely performed in esophagectomy patients, and the decision to insert a CVC should be made based on the patient's perioperative condition. PMID- 27250847 TI - Retrieval of a migrated coil with a handmade microwire-snare device. AB - BACKGROUND: Intraprocedural coil migration during endovascular treatment of intracranial aneurysms is associated with potential vessel occlusion and thromboembolic complications. There is no standard management strategy for coil migration. Here, we describe our experience with using a handmade microwire-snare device (HMD) to retrieve a migrated coil. METHODS: The HMD consists of a 0.017 inch microcatheter, a 0.014-inch microwire, and a 4-0 silk thread. The ring of the microwire-snare device can open, close, and twist in a figure eight pattern for coil entwinement. In addition, the ring can be shaped as needed to navigate tortuous vessels or capture the migrated coil. RESULTS: The HMD was successfully used to retrieve two migrated coils. In the first case, the coil was displaced in the M2 branch of the middle cerebral artery. In the second case, the coil loop prolapsed into the parent artery. In both cases, control cerebral angiograms performed after retrieval confirmed the patency of the vessels and a lack of thromboembolic complications. At the 3-month follow-up, magnetic resonance angiography demonstrated stable patency of the affected vessels. CONCLUSIONS: The HMD is a cost-effective, easy-to-use, safe, and universally available device for retrieving migrated coil(s) during intracranial aneurysm embolization procedures. PMID- 27250848 TI - Internal and external spheno-orbital meningioma varieties: different outcomes and prognoses. AB - BACKGROUND: Internal variation among spheno-orbital meningiomas (SOM) is surgically challenging. Optic canal invasion management is discussed. METHOD: This retrospective study includes 70 patients with SOM who underwent surgery between 1995 and 2012. Preoperative ophthalmological, neurological and aesthetic clinical signs were collected. All patients benefitted from repeated tomography and magnetic resonance imaging (MRI). The surgical team consisted of a neurosurgeon and a plastic surgeon. In the majority of cases, resection was followed by bone reconstruction using an autologous iliac crest graft. The extent of resection was evaluated on the dural and osseous sides. Early clinical outcomes, long-term follow-up, recurrence and adjuvant therapies were reported. RESULTS: The mean age was 52 years old, and 91 % of the patients were women. Initial symptoms primarily included proptosis (65 %), decreased visual acuity (39 %) and soft tissue tumefaction (16 %). We classified 40 cases as the internal variety when considering the inner third of the greater wing of the sphenoid, optic canal, anterior clinoid process or cavernous sinus. The remaining cases were described as the external variety. The complete resection rates for the internal and external varieties were 12 % and 61 %, respectively (P < 0.001). In total, 90 % of cases were grade I meningiomas. For grade I, we reported 30 % recurrence, and 50 % of these cases recurred in the first 2 years. Grade II cases without early adjuvant radiotherapy increased at 2 years. We did not observe any difference in recurrence rate among grade I tumours with or without tumour remnants. At the end of follow-up, visual acuity was stabilised or increased in 88 % of patients. In addition, 14 % of patients experienced persistent pain at the location of the iliac harvesting site. CONCLUSIONS: The internal SOM variety exhibited a reduced total resection rate and a shorter progression-free survival (PFS). Unroofing of the optic canal extended PFS. Among grade I cases, the persistence of a negligible tumour remnant did not alter the probability of recurrence. For superior grades, radiotherapy must be administered in addition to surgery as soon as possible. SOMs require prolonged follow-up. Autologous iliac reconstruction is related to substantial morbidity and could be replaced by prosthetic bone three-dimensional reconstruction. PMID- 27250849 TI - Stent-assisted coil embolization of challenging intracranial aneurysms: initial and mid-term results with low-profile ACCLINO devices. AB - BACKGROUND: Stent-assisted coiling using low-profile, self-expandable and retrievable stents is a valid option in endovascular treatment of challenging intracranial aneurysms. This study aims to evaluate the feasibility and efficacy of ACCLINO 1.9 F and ACCLINO Flex stent systems, designed for use as adjunctive products in coil embolization of intracranial aneurysms. METHODS: Case files of 47 patients, and 52 aneurysms in total, treated with at least one ACCLINO 1.9 F or ACCLINO Flex stent were retrospectively evaluated. Technical success, complications, and angiographic outcomes were assessed based on immediate post procedural controls along with 6th and 12th month angiograms. RESULTS: Mechanical untoward event rate, including asymptomatic complications, is 9.6 % (five out of 52 aneurysms). Failed dual-stenting attempt rate is 15.4 % (two out of 13). Overall procedure-related morbidity is 4.2 % with no neurologic sequelae. Initial occlusion rate is 90.4 % (47 aneurysms). One patient had residual filling in the aneurysm neck, which was stable throughout follow-up. The remaining four cases had spontaneous follow-up occlusion. Recanalization rate at 6th month is 2.1 % with one aneurysm requiring retreatment. One patient was lost to follow-up. There is no mortality associated with treatment. CONCLUSIONS: Stent-assisted coil embolization with ACCLINO stents in single or dual configurations is a feasible treatment option for challenging intracranial aneurysms. Follow-up results are encouraging; techniques were effective in complex cases and there were no clinically significant adverse outcomes. PMID- 27250850 TI - Synaptogenesis: Modulation by Availability of Membrane Phospholipid Precursors. AB - Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory rodents with uridine, DHA and choline enhances the amount of brain membranes as well as synaptic proteins and increases the number of dendritic spines, the essential cytological precursor of new synapses. Hence, the newly formed membranes are utilized for synaptogenesis which underlies increased synaptic functioning evidenced by enhanced neurotransmission and cognition. In addition, this supplementation ameliorates the degeneration in a rat model of Parkinson's disease and mouse models of Alzheimer's disease (AD) when used in combination with several vitamins and cofactors. Hence, accumulating evidence shows that increasing the availability of phospholipid precursors, vitamins and cofactors to the brain through dietary supplementation enhances the formation of new synapses and provides protection under neurodegenerative conditions. The combination has been tested in clinical trials and a medication has been marketed for early-stage AD patients. PMID- 27250851 TI - Exercise prior to assisted fertilization in overweight and obese women (FertilEX): study protocol for a randomized controlled trial. AB - BACKGROUND: Overweight and obese women show reduced conception rates compared to women of normal weight. Insulin resistance and increased amount of visceral fat may be important mechanisms for reduced fertility in these women. Exercise training, in particular with high intensity, has previously been found to improve insulin sensitivity in overweight subjects. This study will assess if regular high-intensity interval training will improve the pregnancy rate after assisted fertilization compared to usual care only in overweight and obese women. We hypothesize that the intervention will improve pregnancy rate and insulin sensitivity compared to the control group. METHODS/DESIGN: The FertilEX study is a randomized, controlled trial in which 140 women with body mass index (BMI) >25 kg/m(2) accepted for assisted fertilization will be randomized (1:1) to an intervention group or a control group. The intervention group will do high intensity interval training three times per week for 10 weeks before assisted fertilization. The control group will receive standard care assisted fertilization only. The primary outcome measure is ongoing pregnancy 7-8 weeks after embryo transfer. Secondary outcome measures are insulin sensitivity, peak oxygen uptake, brachial flow-mediated endothelial function, levels of reproductive hormones, and body composition. DISCUSSION: The results of this trial will provide knowledge about the effects of high-intensity exercise before assisted fertilization in subfertile overweight/obese women. If the intervention leads to beneficial effects on outcome measures, such programs should be considered as part of regular fertility care procedures for this population of women. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01933633 . Registered on 28 August 2013. PMID- 27250853 TI - On-demand calibration and evaluation for electromagnetically tracked laparoscope in augmented reality visualization. AB - PURPOSE: Common camera calibration methods employed in current laparoscopic augmented reality systems require the acquisition of multiple images of an entire checkerboard pattern from various poses. This lengthy procedure prevents performing laparoscope calibration in the operating room (OR). The purpose of this work was to develop a fast calibration method for electromagnetically (EM) tracked laparoscopes, such that the calibration can be performed in the OR on demand. METHODS: We designed a mechanical tracking mount to uniquely and snugly position an EM sensor to an appropriate location on a conventional laparoscope. A tool named fCalib was developed to calibrate intrinsic camera parameters, distortion coefficients, and extrinsic parameters (transformation between the scope lens coordinate system and the EM sensor coordinate system) using a single image that shows an arbitrary portion of a special target pattern. For quick evaluation of calibration results in the OR, we integrated a tube phantom with fCalib prototype and overlaid a virtual representation of the tube on the live video scene. RESULTS: We compared spatial target registration error between the common OpenCV method and the fCalib method in a laboratory setting. In addition, we compared the calibration re-projection error between the EM tracking-based fCalib and the optical tracking-based fCalib in a clinical setting. Our results suggest that the proposed method is comparable to the OpenCV method. However, changing the environment, e.g., inserting or removing surgical tools, might affect re-projection accuracy for the EM tracking-based approach. Computational time of the fCalib method averaged 14.0 s (range 3.5 s-22.7 s). CONCLUSIONS: We developed and validated a prototype for fast calibration and evaluation of EM tracked conventional (forward viewing) laparoscopes. The calibration method achieved acceptable accuracy and was relatively fast and easy to be performed in the OR on demand. PMID- 27250852 TI - Feasibility and usefulness of ultrasonography in idiopathic intracranial hypertension or secondary intracranial hypertension. AB - BACKGROUND: Transorbital sonography (TOS) has been proven to be able to non invasively detect elevated intracranial pressure. In this condition TOS shows an increase in optic nerve sheath diameter (ONSD). It has been suggested that internal jugular vein valve insufficiency (IJVVI) may represent a factor contributing to the pathogenesis of idiopathic intracranial hypertension (IIH). The aim of this study was to investigate whether patients with IIH or secondary IH have higher ONSD values and higher frequency of IJVVI compared to subjects without IH. METHODS: Twenty-one patients with newly diagnosed IIH or secondary IH were prospectively evaluated and compared with 21 age, gender and BMI-matched controls. Experienced vascular sonographers used B-mode TOS to evaluate ONSD, optic nerve diameter (OND) and IJVVI. CSF opening pressures were also measured. RESULTS: ONSD values were significantly higher in patients (6.50 +/- 0.67) than controls (5.73 +/- 0.66; p < 0.0001). No differences were found in OND values between patients (2.99 +/- 0.26) and controls (2.93 +/- 0.41; p = 0.574). No correlation was demonstrated between ONSD and CSF opening pressure (r = 0,086) (p = 0.73). No difference in frequency of IJVVI between patients (11/42 valves, 26 %) and controls (9/42, 21 %) was observed (p = 0.777). CONCLUSIONS: Increased ONSD values detected by TOS support the diagnosis of IH. Our results do not support the hypothesis of a venous congestion as a potential factor contributing to the pathogenesis of IIH. TRIAL REGISTRATION: Not applicable. Observational, non-interventional study. PMID- 27250854 TI - miLBP: a robust and fast modality-independent 3D LBP for multimodal deformable registration. AB - PURPOSE: Computer-assisted intervention often depends on multimodal deformable registration to provide complementary information. However, multimodal deformable registration remains a challenging task. METHODS: This paper introduces a novel robust and fast modality-independent 3D binary descriptor, called miLBP, which integrates the principle of local self-similarity with a form of local binary pattern and can robustly extract the similar geometry features from 3D volumes across different modalities. miLBP is a bit string that can be computed by simply thresholding the voxel distance. Furthermore, the descriptor similarity can be evaluated efficiently using the Hamming distance. RESULTS: miLBP was compared to vector-valued self-similarity context (SSC) in artificial image and clinical settings. The results show that miLBP is more robust than SSC in extracting local geometry features across modalities and achieved higher registration accuracy in different registration scenarios. Furthermore, in the most challenging registration between preoperative magnetic resonance imaging and intra-operative ultrasound images, our approach significantly outperforms the state-of-the-art methods in terms of both accuracy ([Formula: see text]) and speed (29.2 s for one case). CONCLUSIONS: Registration performance and speed indicate that miLBP has the potential of being applied to the time-sensitive intra-operative computer assisted intervention. PMID- 27250855 TI - Soft tissue motion tracking with application to tablet-based incision planning in laser surgery. AB - PURPOSE: Recent research has revealed that incision planning in laser surgery deploying stylus and tablet outperforms micromanipulator control. However, vision based adaption to dynamic surgical scenes has not been addressed so far. In this study, scene motion compensation for tablet-based planning by means of tissue deformation tracking is discussed. METHODS: A stereo-based method for motion tracking with piecewise affine deformation modeling is presented. Proposed parametrization relies on the epipolar constraint to enforce left-right consistency in the energy minimization problem. Furthermore, the method implements illumination-invariant tracking and appearance-based occlusion detection. Performance is assessed on laparoscopic and laryngeal in vivo data. In particular, tracking accuracy is measured under various conditions such as occlusions and simulated laser cuttings. Experimental validation is extended to a user study conducted on a tablet-based interface that integrates the tracking for image stabilization. RESULTS: Tracking accuracy measurement reveals a root-mean square error of 2.45 mm for the laparoscopic and 0.41 mm for the laryngeal dataset. Results successfully demonstrate stereoscopic tracking under changes in illumination, translation, rotation and scale. In particular, proposed occlusion detection scheme can increase robustness against tracking failure. Moreover, assessed user performance indicates significantly increased path tracing accuracy and usability if proposed tracking is deployed to stabilize the view during free hand path definition. CONCLUSION: The presented algorithm successfully extends piecewise affine deformation tracking to stereo vision taking the epipolar constraint into account. Improved surgical performance as demonstrated for laser incision planning highlights the potential of presented method regarding further applications in computer-assisted surgery. PMID- 27250856 TI - Genomic resources and draft assemblies of the human and porcine varieties of scabies mites, Sarcoptes scabiei var. hominis and var. suis. AB - BACKGROUND: The scabies mite, Sarcoptes scabiei, is a parasitic arachnid and cause of the infectious skin disease scabies in humans and mange in other animal species. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where secondary group A streptococcal and Staphylococcus aureus infections of scabies sores are thought to drive the high rate of rheumatic heart disease and chronic kidney disease. RESULTS: We sequenced the genome of two samples of Sarcoptes scabiei var. hominis obtained from unrelated patients with crusted scabies located in different parts of northern Australia using the Illumina HiSeq. We also sequenced samples of Sarcoptes scabiei var. suis from a pig model. Because of the small size of the scabies mite, these data are derived from pools of thousands of mites and are metagenomic, including host and microbiome DNA. We performed cleaning and de novo assembly and present Sarcoptes scabiei var. hominis and var. suis draft reference genomes. We have constructed a preliminary annotation of this reference comprising 13,226 putative coding sequences based on sequence similarity to known proteins. CONCLUSIONS: We have developed extensive genomic resources for the scabies mite, including reference genomes and a preliminary annotation. PMID- 27250857 TI - The reciprocal interaction of sympathetic nervous system and cAMP-PKA-NF-kB pathway in immune suppression after experimental stroke. AB - BACKGROUND: Sympathetic nervous system(SNS) is involved in the mechanism of immune suppression after stroke. Furthermore, as the pro-inflammatory effect of nuclear factor kappa B(NF-kB) is inhibited after stroke, which is regulated by cyclic adenosine monophosphate(cAMP) and proteinkinase A(PKA). The cAMP-PKA-NF-kB pathway might play an important role in noradrenergic-mediated immune dysfunction. AIM: The purpose of our research is to analyze how SNS interfere with the immune system after acute stroke and the underlying mechanism of cAMP PKA-NF-kB pathway in regulating the inflammation. METHODS: 32 healthy male Sprague-Dawley rats were divided into 4 groups equally and randomly (1) Sham operation group; (2) middle cerebral artery occlusion; (MCAO) control group; (3) propranolol MCAO group; (4) isopropylarterenol sham group. 72h later after MCAO or sham operation, tumor necrosis factor-alpha(TNF-alpha)and interleukine-10(IL 10) in serum as well as cAMP, PKA and NF-kB in spleen cells were tested. RESULTS: TNF-alpha decreased while IL-10 increased in serum after acute ischemia stroke (p<0.05). Meanwhile, the levels of cAMP and PKA in spleen both increased in MCAO model while the expression of NF-kB was inhibited (p<0.05). When propranolol was used to inhibit SNS, all of the results reversed (p<0.05). But the reversed results were still significantly different from the sham operation group (p<0.05). Isopropylarterenol administrated rats appeared the same trend as MCAO group when compared to the sham operation group (p<0.05). However, the differences still existed (p<0.05). CONCLUSION: On account of the SNS activation after stroke, epinephrine activates the expression of cAMP, which further increases the level of PKA. Therefore, the level of nuclear factor NF-kB is down regulated. Since the pro-inflammatory effect of NF-kB slacked, the immune system may be inhibited after stroke. PMID- 27250858 TI - Changes of gamma-band oscillatory activity to tonic muscle pain. AB - It is well know that phasic pain could induce suppression of alpha oscillations and enhancement of gamma oscillations. However, the cortical responses to tonic pain, especially tonic pain originating from deep tissue, which was proposed to better resemble the clinical pain, are not well understood. Here we aimed to investigate electroencephalographic (EEG) responses to tonic muscle pain. EEG signals and pain perceptions of three order-counterbalanced conditions: innocuous condition (A, infusion of isotonic saline), noxious conditions with low (B) and medium (C) intensities (infusion of hypertonic saline) were recorded from 43 subjects. We observed the enhancement of gamma oscillations in frontal-central region in condition C, as compared to either condition A or B. Positive relationship between the amplitude of gamma oscillations and pain intensity was also observed in frontal-central region. Therefore, we provide novel evidence for the encoding of frontal-central gamma oscillations in tonic pain processing. PMID- 27250859 TI - Lower limb joint angles and ground reaction forces in forefoot strike and rearfoot strike runners during overground downhill and uphill running. AB - This study investigated the normal and parallel ground reaction forces during downhill and uphill running in habitual forefoot strike and habitual rearfoot strike (RFS) runners. Fifteen habitual forefoot strike and 15 habitual RFS recreational male runners ran at 3 m/s +/- 5% during level, uphill and downhill overground running on a ramp mounted at 6 degrees and 9 degrees . Results showed that forefoot strike runners had no visible impact peak in all running conditions, while the impact peaks only decreased during the uphill conditions in RFS runners. Active peaks decreased during the downhill conditions in forefoot strike runners while active loading rates increased during downhill conditions in RFS runners. Compared to the level condition, parallel braking peaks were larger during downhill conditions and parallel propulsive peaks were larger during uphill conditions. Combined with previous biomechanics studies, our findings suggest that forefoot strike running may be an effective strategy to reduce impacts, especially during downhill running. These findings may have further implications towards injury management and prevention. PMID- 27250860 TI - Assessing Heart Rate at Birth: Auscultation Is Still the Gold Standard. PMID- 27250861 TI - Comments on 'Multiplicity adjustments in testing for bioequivalence'. PMID- 27250862 TI - Plasmon-Driven Dynamic Response of a Hierarchically Structural Silver-Decorated Nanorod Array for Sub-10 nm Nanogaps. AB - Plasmonic nanogaps serve as a useful configuration for light concentration and local field amplification owing to the extreme localization of surface plasmons. Here, a smart plasmonic nanogap device is fabricated by the dynamic response of an Ag decorated hierarchically structural vertical polymer nanorod array under the light irradiation. Seven nanorods in one unit bend because of plasmonic heating effect and they are centrally collected due to the attraction of the plasmon-induced polaritons, leading to the significantly enhanced local electromagnetic field at the sub-10 nm gaps among the constricted nanorod tops. Compared with tuning capillarity in microscale by wetting and drying, using light as external stimuli is much easier and more tunable in nanoscale. This plasmonic nanogap device is used for a surface-enhanced Raman scattering (SERS) substrate. Its hydrophobic surface with a contact angle of 142 degree can make the probed aqueous solution only access to the Ag tips of nanorods. Thus, the analytes can be driven to the "hot spot" regions where located at the tops of nanorods during the solvent evaporation process, which is beneficial to SERS detection. Discovery of this smart plasmon-driven process broadens the scope for further functionality of both the dynamic nanostructure design and the smart plasmonic devices in the communities of chemistry, biomedicine, and microfluidic engineering. PMID- 27250863 TI - Comparison of long-term outcomes of bare-metal and paclitaxel-eluting stents in New York. AB - AIMS: Bare-metal stents (BMS) as the first-generation coronary stent and paclitaxel-eluting stents (PES) as a first-generation drug-eluting stent have been employed in percutaneous coronary intervention (PCI). However, the long-term comparative effectiveness of BMS versus PES in real practice remains unclear. To assess long-term outcomes for patients undergoing PCI with either BMS or PES placement and to determine comparative effectiveness of BMS versus PES in six 'off-label' and two 'high-risk' patient subgroups. METHODS AND RESULTS: A longitudinal database was created by linking the New York State cardiac registries, statewide hospital discharge data, the National Death Index and the US Census file (2010) for patients undergoing PCI with BMS or PES placement in 2006 and 2007. Outcomes included all-cause mortality, acute myocardial infarction (AMI), target vessel PCI (TVPCI) and target vessel coronary artery bypass graft (TVCABG) surgery for a 5.5-year follow-up period. A total of 13 879 propensity score matched pairs were compared with respect to outcomes using Kaplan-Meier method with further adjustment using Cox proportional hazards regression. At 5.5 years, PES use was associated with significantly lower mortality (adjusted hazard ratio (AHR): 0.73, 95% confidence interval < CI>: 0.69-0.77), AMI (AHR: 0.90, 95% CI: 0.83-0.98), TVPCI (AHR: 0.92, 95% CI: 0.86-0.99) and TVCABG (AHR, 0.63, 95% CI: 0.53-0.74). For 'off-label' and 'high-risk' subgroups, PES was associated with lower mortality and improved/similar AMI, TVPCI and TVCABG rates relative to BMS. CONCLUSIONS: Compared with BMS, PES was associated with improved mortality and better or comparable AMI, TVPCI and TVCABG outcomes at 5.5 years. PMID- 27250864 TI - CHIP: Facilitating Interprofessional and Culturally Competent Patient Care Through Experiential Learning in China. AB - Health care professionals have advocated for educating culturally competent practitioners. Immersion in international experiences has an impact on student cultural competency and interprofessional development. The China Honors Interprofessional Program (CHIP) at a university in the Midwest is designed to increase students' cultural competency and interprofessional development. From 2009 to 2013, a total of 25 professional students including twelve occupational therapy students, ten physical therapy students and three nursing students were enrolled in the programme. Using a one group pre and posttest research design, this study evaluated the impact of CHIP on the participating students. Both quantitative and qualitative data were collected in the study. Findings of the study revealed that CHIP has impact on students' cultural competency and professional development including gaining appreciation and understanding of the contributions of other healthcare professionals and knowledge and skills in team work. The findings of the study suggested that international immersion experience such as CHIP is an important way to increase students' cultural competency and interprofessional knowledge and skills. Limitations of the study included the small sample in the study, indirect outcome measures and the possible celling effect of the instruments of the study. Future research studies should include a larger and more representative sample, direct outcome measures such as behaviour observation and more rigorous design such as prospective experimental comparison group design. Future research should also examine the long-term effects of international experience on the professional development of occupational therapy students. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27250865 TI - Multidimensional biases, gaps and uncertainties in global plant occurrence information. AB - Plants are a hyperdiverse clade that plays a key role in maintaining ecological and evolutionary processes as well as human livelihoods. Biases, gaps and uncertainties in plant occurrence information remain a central problem in ecology and conservation, but these limitations remain largely unassessed globally. In this synthesis, we propose a conceptual framework for analysing gaps in information coverage, information uncertainties and biases in these metrics along taxonomic, geographical and temporal dimensions, and apply it to all c. 370 000 species of land plants. To this end, we integrated 120 million point-occurrence records with independent databases on plant taxonomy, distributions and conservation status. We find that different data limitations are prevalent in each dimension. Different metrics of information coverage and uncertainty are largely uncorrelated, and reducing taxonomic, spatial or temporal uncertainty by filtering out records would usually come at great costs to coverage. In light of these multidimensional data limitations, we discuss prospects for global plant ecological and biogeographical research, monitoring and conservation and outline critical next steps towards more effective information usage and mobilisation. Our study provides an empirical baseline for evaluating and improving global floristic knowledge, along with a conceptual framework that can be applied to study other hyperdiverse clades. PMID- 27250866 TI - Stromal Tissue Rigidity Promotes Mesenchymal Stem Cell-Mediated Corneal Wound Healing Through the Transforming Growth Factor beta Signaling Pathway. AB - The healing of a corneal epithelial defect is essential for preventing infectious corneal ulcers and subsequent blindness. We previously demonstrated that mesenchymal stem cells (MSCs) in the corneal stroma, through a paracrine mechanism, yield a more favorable therapeutic benefit for corneal wound re epithelialization than do MSCs in the corneal epithelium. In this study, MSCs were grown on a matrix with the rigidity of the physiological human vitreous (1 kPa), corneal epithelium (8 kPa), or corneal stroma (25 kPa) for investigating the role of corneal tissue rigidity in MSC functions regarding re epithelialization promotion. MSC growth on a 25-kPa dish significantly promoted the wound healing of human corneal epithelial (HCE-T) cells. Among growth factors contributing to corneal epithelial wound healing, corneal stromal rigidity selectively enhanced transforming growth factor-beta (TGF-beta) secretion from MSCs. Inhibitors of TGF-beta pan receptor, TGF-beta receptor 1, and Smad2 dose dependently abrogated MSC-mediated HCE-T wound healing. Furthermore, MSCs growth on a matrix with corneal stromal rigidity enhanced the ability of themselves to promote corneal re-epithelialization by activating matrix metalloproteinase (MMP) expression and integrin beta1 production in HCE-T cells through TGF-beta signaling pathway activation. Smad2 activation resulted in the upregulation of MMP-2 and -13 expression in HCE-T cells, whereas integrin beta1 production favored a Smad2-independent TGF-beta pathway. Altogether, we conclude that corneal stromal rigidity is a critical factor for MSC-induced promotion of corneal re-epithelialization. The activation of the TGF-beta signaling pathway, which maintains the balance between integrin and MMP expression, in HCE-T cells is the major pathway responsible for MSC-mediated wound healing. Stem Cells 2016;34:2525-2535. PMID- 27250867 TI - Effect of Promoter Polymorphisms on Cytokine Concentration in Preterm Breast Milk and Subsequent Infant Outcomes. AB - BACKGROUND: Breast milk concentrations of immune components are variable between women and interleukin (IL) differences may be associated with infant outcomes. Molecular mechanisms for milk variability remain unknown. OBJECTIVE: The aims were to (1) examine the relationship between maternal IL genotypes and milk concentrations of IL4, IL6, and IL10, (2) describe the trajectories of milk IL change, (3) examine whether maternal IL genotypes predict IL trajectories and/or average weekly IL concentration, and (4) examine if weekly IL levels and/or IL trajectories are associated with infant outcomes. METHODS: Milk aliquots were collected from each feeding of mother's own milk and pooled weekly. DNA was extracted from 1 sample of each mother's breast milk whey (n = 64), and single nucleotide polymorphisms (SNPs) of IL genes were genotyped. Milk IL concentrations were measured and trajectory analysis examined IL milk change over time. Multivariate breast milk IL concentration analyses controlled for gestational age and prepregnancy body mass index. Multivariate infant outcome (n = 73) analyses controlled for gestational age and the ratio of human milk to total milk. RESULTS: Trajectory analysis resulted in linear group shapes, with 2 distinct subgroups in IL6 and 3 subgroups in IL4 and IL10. Trajectory groups trended toward significance with calprotectin, intraventricular hemorrhage, and blood transfusions. Multivariate analyses resulted in trending associations between maternal SNPs and subsequent IL6 and IL10 milk levels. There was a trending relationship between IL milk levels and both fecal calprotectin and intraventricular hemorrhage. CONCLUSION: Maternal IL SNPs may affect IL breast milk levels and IL milk levels may be associated with infant outcomes. PMID- 27250869 TI - Effect of emplaced nZVI mass and groundwater velocity on PCE dechlorination and hydrogen evolution in water-saturated sand. AB - The effect of nZVI mass loading and groundwater velocity on the tetrachloroethylene (PCE) dechlorination rate and the hydrogen evolution rate for poly(maleic acid-co-olefin) (MW=12K) coated nZVI was examined. In batch reactors, the PCE reaction rate constant (3.7*10-4Lhr-1m-2) and hydrogen evolution rate constant (1.4 nanomolLhr-1m-2) were independent of nZVI concentration above 10g/L, but the PCE dechlorination rate decreased and the hydrogen evolution rate increased for nZVI concentration below 10g/L. The nonlinearity between nZVI mass loading and PCE dechlorination and H2 evolution was explained by differences in pH and Eh at each nZVI mass loading; PCE reactivity increased when solution Eh decreased, and the H2 evolution rate increased with decreasing pH. Thus, nZVI mass loading of <5g/L yields lower reactivity with PCE and lower efficiency of Fe degrees utilization than for higher nZVI mass loading. The PCE dechlorination rate increased with increasing pore-water velocity, suggesting that mass transfer limits the reaction at low porewater velocity. Overall, this work suggests that design of nZVI-based reactive barriers for groundwater treatment should consider the non-linear effects of both mass loading and flow velocity on performance and expected reactive lifetime. PMID- 27250868 TI - A meta-analysis of extracorporeal shock wave therapy for Peyronie's disease. AB - The efficiency of extracorporeal shock wave therapy (ESWT) for Peyronie's disease (PD) has been controversial for a very long time. We aimed to evaluate the efficiency of ESWT for PD and provide possible evidence on the basis of a meta analysis of existing comparative studies. All controlled studies, including randomized controlled trials (RCTs), cohort studies and case-control studies, that focused on the efficiency of ESWT for PD, were prospectively identified through comprehensive searches of PubMed, the Cochrane Library and Embase databases. We conducted a meta-analysis of these studies. Six studies including 443 patients were selected for the meta-analysis. Pooling data of these studies showed that ESWT could significantly increase the percentage of men with lessening of penile plaques (odds ratio (OR) 2.07, 95% confidence interval (CI) 1.11-3.85, P=0.02), relief of pain (OR 4.46, 95% CI 2.29-8.68, P<0.0001) and complete remission of pain (OR 5.86, 95% CI 2.66-12.92, P<0.0001). However, insignificant differences were found in improvement of penile curvature (OR 1.88, 95% CI 0.97-3.65, P=0.06) and sexual function (OR 2.22, 95% CI 0.69-7.11, P=0.18) between ESWT and placebo groups. Further, similar results were shown for sensitivity and publication bias analysis when only RCTs were included. However, sporadic complications caused by ESWT were reported, but no patient needed additional treatment aside from conservative observation. ESWT may be an effective and safe treatment for lessening of penile plaques and relieving pain for men with PD, but not for improving of penile curvature and sexual function. PMID- 27250870 TI - The response of an egg parasitoid to substrate-borne semiochemicals is affected by previous experience. AB - Animals can adjust their behaviour according to previous experience gained during foraging. In parasitoids, experience plays a key role in host location, a hierarchical process in which air-borne and substrate-borne semiochemicals are used to find hosts. In nature, chemical traces deposited by herbivore hosts when walking on the plant are adsorbed by leaf surfaces and perceived as substrate borne semiochemicals by parasitoids. Chemical traces left on cabbage leaves by adults of the harlequin bug (Murgantia histrionica) induce an innate arrestment response in the egg parasitoid Trissolcus brochymenae characterized by an intense searching behaviour on host-contaminated areas. Here we investigated whether the T. brochymenae response to host walking traces left on leaf surfaces is affected by previous experience in the context of parasitoid foraging behaviour. We found that: 1) an unrewarded experience (successive encounters with host-contaminated areas without successful oviposition) decreased the intensity of the parasitoid response; 2) a rewarded experience (successful oviposition) acted as a reinforcing stimulus; 3) the elapsed time between two consecutive unrewarded events affected the parasitoid response in a host-gender specific manner. The ecological role of these results to the host location process of egg parasitoids is discussed. PMID- 27250871 TI - Subliminal gait initiation deficits in rapid eye movement sleep behavior disorder: A harbinger of freezing of gait? AB - BACKGROUND: Muscle activity during rapid eye movement sleep is markedly increased in people with rapid eye movement sleep behavior disorder and people with Parkinson's disease (PD) who have freezing of gait. This study examined whether individuals with rapid eye movement sleep behavior disorder who do not have a diagnosis of PD show abnormalities in gait initiation that resemble the impairments observed in PD and whether there is a relationship between these deficits and the level of rapid eye movement sleep without atonia. METHODS: Gait initiation and polysomnography studies were conducted in 4 groups of 10 participants: rapid eye movement sleep behavior disorder, PD with and without freezing of gait, and controls. RESULTS: Significant reductions were seen in the posterior shift of the center of pressure during the propulsive phase of gait initiation in the groups with rapid eye movement sleep behavior disorder and PD with freezing of gait when compared with controls and PD nonfreezers. These reductions negatively correlated with the amount of rapid eye movement sleep without atonia. The duration of the initial dorsiflexor muscle burst during gait initiation was significantly reduced in both PD groups and the rapid eye movement sleep behavior disorder cohort. CONCLUSIONS: These results provide evidence that people with rapid eye movement sleep behavior disorder, prior to a diagnosis of a degenerative neurologic disorder, show alterations in the coupling of posture and gait similar to those seen in PD. The correlation between increased rapid eye movement sleep without atonia and deficits in forward propulsion during the push off phase of gait initiation suggests that abnormities in the regulation of muscle tone during rapid eye movement sleep may be related to the pathogenesis of freezing of gait. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27250872 TI - Single-trial prediction of reaction time variability from MEG brain activity. AB - Neural activity prior to movement onset contains essential information for predictive assistance for humans using brain-machine-interfaces (BMIs). Even though previous studies successfully predicted different goals for upcoming movements, it is unclear whether non-invasive recording signals contain the information to predict trial-by-trial behavioral variability under the same movement. In this paper, we examined the predictability of subsequent short or long reaction times (RTs) from magnetoencephalography (MEG) signals in a delayed reach task. The difference in RTs was classified significantly above chance from 550 ms before the go-signal onset using the cortical currents in the premotor cortex. Significantly above-chance classification was performed in the lateral prefrontal and the right inferior parietal cortices at the late stage of the delay period. Thus, inter-trial variability in RTs is predictable information. Our study provides a proof-of-concept of the future development of non-invasive BMIs to prevent delayed movements. PMID- 27250874 TI - A single homeobox gene triggers phase transition, embryogenesis and asexual reproduction. AB - Plants characteristically alternate between haploid gametophytic and diploid sporophytic stages. Meiosis and fertilization respectively initiate these two different ontogenies(1). Genes triggering ectopic embryo development on vegetative sporophytic tissues are well described(2,3); however, a genetic control of embryo development from gametophytic tissues remains elusive. Here, in the moss Physcomitrella patens we show that ectopic overexpression of the homeobox gene BELL1 induces embryo formation and subsequently reproductive diploid sporophytes from specific gametophytic cells without fertilization. In line with this, BELL1 loss-of-function mutants have a wild-type phenotype, except that their egg cells are bigger and unable to form embryos. Our results identify BELL1 as a master regulator for the gametophyte-to-sporophyte transition in P. patens and provide mechanistic insights into the evolution of embryos that can generate multicellular diploid sporophytes. This developmental innovation facilitated the colonization of land by plants about 500 million years ago(4) and thus shaped our current ecosystems. PMID- 27250873 TI - Prevalence and correlates of valvular heart diseases in the elderly population in Hubei, China. AB - We sought to determine the prevalence and correlates of valvular heart diseases (VHD) in the elderly population. The participants' personal information, medical history, behavioral habits and clinical status were assessed by questionnaire, while the left ventricular dimensions, function and the presence and severity of VHD were evaluated by transthoracic echocardiography. This study analyzed the data of 3948 participants who were older than 60 years. Significant VHD was present in 1.93% of participants; the standardized prevalence of VHD among the elderly population in Hubei was 2.05% (95% CI: 1.61-2.49). The most frequent VHD was aortic regurgitation, followed by tricuspid regurgitation, mitral regurgitation and multiple valve diseases. Univariate analysis results indicated that compared with participants without VHD, those with VHD were older (p < 0.001), with a higher body mass index (BMI) (p < 0.001), were more likely to smoke (p = 0.04), and had higher rates of coronary artery disease (CAD) (p < 0.001) and arrhythmia (p < 0.001). The results of multinomial regression analysis of complex sampling indicated that combined mitral and aortic valve diseases were related to older age, male sex and smoking; CAD was associated with single left sided VHD. PMID- 27250876 TI - Nanoparticle-Templated Formation and Growth Mechanism of Curved Protein Polymer Fibrils. AB - We investigated the growth of biosynthetic protein polymers with templated curvature on pluronic nanospheres. The protein has a central silk-like block containing glutamic residues (S(E)) and collagen-like end-blocks (C). The S(E) blocks stack into filaments when their charge is removed (pH <5). Indeed, at low pH curved and circular fibers are formed at the surface of the nanospheres, which keep their shape after removal of the pluronics. The data reveal the mechanism of the templated fibril-growth: The growth of protein assemblies is nucleated in solution; small protein fibrils adsorb on the nanospheres, presumably due to hydrogen bond formation between the silk-like blocks and the pluronic PEO blocks. The surface of the pluronic particles templates further growth. At relatively low protein/pluronic weight ratios, only a fraction of the nanospheres bears protein fibers, pointing to a limiting amount of nuclei in solution. Because the nanospheres capture fibrils at an early stage of growth, they can be used to separate growth and nucleation rates in protein fibril formation. Moreover, the nanoparticle-templated growth of stable curved fibers opens ways to build proteinaceous nanocapsules from designed protein polymers. PMID- 27250877 TI - Wafer-scale fabrication and growth dynamics of suspended graphene nanoribbon arrays. AB - Adding a mechanical degree of freedom to the electrical and optical properties of atomically thin materials can provide an excellent platform to investigate various optoelectrical physics and devices with mechanical motion interaction. The large scale fabrication of such atomically thin materials with suspended structures remains a challenge. Here we demonstrate the wafer-scale bottom-up synthesis of suspended graphene nanoribbon arrays (over 1,000,000 graphene nanoribbons in 2 * 2 cm(2) substrate) with a very high yield (over 98%). Polarized Raman measurements reveal graphene nanoribbons in the array can have relatively uniform-edge structures with near zigzag orientation dominant. A promising growth model of suspended graphene nanoribbons is also established through a comprehensive study that combined experiments, molecular dynamics simulations and theoretical calculations with a phase-diagram analysis. We believe that our results can contribute to pushing the study of graphene nanoribbons into a new stage related to the optoelectrical physics and industrial applications. PMID- 27250875 TI - Specific control of Arabidopsis BAK1/SERK4-regulated cell death by protein glycosylation. AB - Precise control of cell death is essential for the survival of all organisms. Arabidopsis thaliana BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1 (BAK1) and somatic embryogenesis receptor kinase 4 (SERK4) redundantly and negatively regulate cell death through elusive mechanisms. By deploying a genetic screen for suppressors of cell death triggered by virus-induced gene silencing of BAK1/SERK4 on Arabidopsis knockout collections, we identified STT3a, a protein involved in N-glycosylation modification, as an important regulator of bak1/serk4 cell death. Systematic investigation of glycosylation pathway and endoplasmic reticulum (ER) quality control (ERQC) components revealed distinct and overlapping mechanisms of cell death regulated by BAK1/SERK4 and their interacting protein BIR1. Genome-wide transcriptional analysis revealed the activation of members of cysteine-rich receptor-like kinase (CRK) genes in the bak1/serk4 mutant. Ectopic expression of CRK4 induced STT3a/N-glycosylation dependent cell death in Arabidopsis and Nicotiana benthamiana. Therefore, N glycosylation and specific ERQC components are essential to activate bak1/serk4 cell death, and CRK4 is likely to be among client proteins of protein glycosylation involved in BAK1/SERK4-regulated cell death. PMID- 27250879 TI - Handedness is related to neural mechanisms underlying hemispheric lateralization of face processing. AB - While the right-hemispheric lateralization of the face perception network is well established, recent evidence suggests that handedness affects the cerebral lateralization of face processing at the hierarchical level of the fusiform face area (FFA). However, the neural mechanisms underlying differential hemispheric lateralization of face perception in right- and left-handers are largely unknown. Using dynamic causal modeling (DCM) for fMRI, we aimed to unravel the putative processes that mediate handedness-related differences by investigating the effective connectivity in the bilateral core face perception network. Our results reveal an enhanced recruitment of the left FFA in left-handers compared to right handers, as evidenced by more pronounced face-specific modulatory influences on both intra- and interhemispheric connections. As structural and physiological correlates of handedness-related differences in face processing, right- and left handers varied with regard to their gray matter volume in the left fusiform gyrus and their pupil responses to face stimuli. Overall, these results describe how handedness is related to the lateralization of the core face perception network, and point to different neural mechanisms underlying face processing in right- and left-handers. In a wider context, this demonstrates the entanglement of structurally and functionally remote brain networks, suggesting a broader underlying process regulating brain lateralization. PMID- 27250881 TI - Weekly versus Three-Weekly Cisplatin-based Concurrent Chemoradiotherapy as definitive treatment in Head and Neck Cancer- Where do we stand? AB - PURPOSE: To compare toxicity, compliance, and early response of weekly and 3 weekly cisplatin administration concurrent with radiotherapy as definitive treatment in locally advanced squamous cell carcinoma head and neck. MATERIALS AND METHODS: Patients with histologically proven stage III - IV B head and neck carcinoma presenting from June 2013 to March 2014 were randomly assigned to weekly (35 mg/m2, 6 cycles; arm A) and 3 weekly (100 mg/m2, 3 cycles; arm B) cisplatin with concurrent radiotherapy. RESULTS: 60 patients were randomly assigned to treatment, 30 in each arm. Median follow-up was 8 months (range 4 13). There was no significant difference in grade 3 mucositis between the two arms (75.9% vs 70%, p = 0.20). Grade 3 neutropenia was more frequent in arm B (55.2% vs 26.7%, p = 0.01). Hypomagnesemia was the commonest electrolyte imbalance and it was significantly higher in arm B (60% vs 20%, p = 0.001). Completion rate of scheduled chemotherapy cycles was higher for patients receiving weekly regimen. Response at 3 months was similar for all the patients {Complete Response (66.7% vs 62.1%), p = 0.200}. Our data suggested that there is a reduced need of hospitalization and supportive care measures for patients receiving weekly cisplatin with RT (p = 0.05). CONCLUSIONS: Weekly cisplatin 35 mg/m2 chemotherapy concurrent with radiotherapy is equally effective and less toxic in terms of neutropenia, hypomagnesemia and need for supportive measures than the conventional 3 weekly cisplatin 100 mg/m2 regimen. PMID- 27250882 TI - Stereotactic Hypofractionated Accurate Radiotherapy of the Prostate (SHARP), 36.25 Gy in Five Fractions for Localized Disease: A Case Series Results from King Faisal Specialist Hospital, Saudi Arabia. AB - PURPOSE: To evaluate the feasibility, efficacy and toxicity of stereotactic hypofractionated accurate radiotherapy (SHARP) for localized prostate cancer. METHODS AND MATERIALS: The current series of SHARP included six patients with localized prostate cancer treated with 36.25 Gy in 5 fractions by Cyber-knife. Non-coplanar conformal fields and daily stereotactic localization of implanted fiducials were used for treatment. Acute and Late Genitourinary (GU) and gastrointestinal (GI) toxicity were evaluated by Common Toxicity Criteria (CTC). Prostate-specific antigen (PSA) values and self-reported sexual function were recorded at 3 months interval at first two years then every 6 months thereafter. RESULTS: The median follow-up is 32 months. Acute toxicity Grade 1 (GU) noted in four cases and two cases were Grade II; Grade I (GI) was in five cases and one patient in Grade II; also with regards to late toxicity, Grade 1 (GU) and (GI) was present in all cases. No patient has experienced grade 3 or greater acute or late toxicity. Regarding sexual activity, three patients reported impotency before and after therapy and all of them have insulin dependent diabetes mellitus and ischemic heart disease; fourth patient has developed impotence and the other two patients developed no changes as before radiation. The mean basal PSA was 8 ng/ml and became 0.658 ng/ml. CONCLUSIONS: SHARP for localized prostate cancer is feasible with minimal acute or late toxicity. Dose escalation should be possible. MRI guided target volume delineation and intrafraction prostate motion tracking with real-time beam adjustment are critical for safe high dose per fraction prostate SBRT. PMID- 27250880 TI - PepT1 Expression Helps Maintain Intestinal Homeostasis by Mediating the Differential Expression of miRNAs along the Crypt-Villus Axis. AB - In the jejunum, PepT1 is particularly enriched in the well-differentiated absorptive epithelial cells in the villi. Studies of expression and function of PepT1 along the crypt-villus axis demonstrated that this protein is crucial to the process of di/tripeptide absorption. We recently exhibited that PepT1 plays an important role in multiple biological functions, including the ability to regulate the expression/secretion of specific microRNAs (miRNAs) and the expression levels of multiple proteins. In this study, we observed that PepT1 knockout (KO) mice exhibited reduced body weight and shorten intestinal microvilli. We then examined the expression levels of various miRNAs and their target proteins along the crypt-villi axis in the jejunum of PepT1 KO mice. We found that PepT1 KO altered the distribution of miRNAs along the crypt-villus axis and changed the miRNA profiles of both villi and crypts. Using miRNA-target prediction and 2D-DIGE/mass spectrometry on villi and crypts samples, we found that ablation of PepT1 further directly or indirectly altered expression levels of certain protein targets. Collectively, our results suggest that PepT1 contributes to maintain balance of homeostasis and proper functions in the small intestine, and dysregulated miRNAs and proteins along the crypt-villus axis are highly related to this process. PMID- 27250883 TI - FOLFOX as Perioperative Chemotherapy of localized Gastric Cancer: Efficacy and Tolerance. AB - BACKGROUND: Use of perioperative chemotherapy had significantly improved prognosis of localized gastric cancer. Two studies have validated this approach using cisplatin based chemotherapy despite important toxicities. We conducted this study with the aim to evaluate efficacy and toxicity of FOLFOX regimen in this setting. MATERIAL AND METHODS: This is a retrospective study including patients followed for gastric cancer in the Oncology Department of the military hospital Mohamed V in Rabat, Morocco over a period of 7 years from 2007 to 2013. Patients received 4 cycles of mFOLFOX as perioperative regimen. Assessment of tumor response after completion of preoperative chemotherapy was granted by comparative CT scan, tumor markers measurements and R0 surgery rate.Adverse events were graded according to classification of the National Cancer Institute Common Toxicity Criteria version 4.0. RESULTS: Thirty-one patients were included in this study. Use of preoperative chemotherapy showed partial response in fourteen patients (45.1%), stabilization in fifteen patients (48.4%). Tumor markers CEA and CA 19- 9 were significantly decreased. R0 resection rate was 83.87%. Only 2 (6.45%) cases of grade 3/4 hematologic toxicity were reported in our study. Achieving programmed postoperative chemotherapy was possible in 72.41% of patients. CONCLUSIONS: Our study is limited by the retrospective design and small sample size but FOLFOX chemotherapy seems effective and well tolerated in this setting and its place deserves to be studied in a larger study. PMID- 27250884 TI - Evaluation of localization uncertainty of fiducial markers due to length and position variations induced by motion in CT imaging by measurement and modeling. AB - PURPOSE: To quantify the variations in the length and position of fiducial markers induced by motion in axial (ACT), helical (HCT) and cone-beam CT (CBCT) imaging and associated uncertainty in image-guided radiotherapy (IGRT) by measurement and modeling. METHODS: A mobile thorax phantom containing markers of various lengths was imaged using ACT, HCT and CBCT imaging. The phantom was imaged while stationary and moving where it was moved sinusoidally with different motion amplitudes and frequency. An analytical motion model was developed that predicts the localization accuracy of IGRT based on fiducial markers in mobile phantom with ACT, HCT and CBCT. RESULTS: The apparent lengths of the markers varied with the different motion patterns and CT imaging modalities. In CBCT, the apparent length of the markers increased linearly with the motion amplitude for both half-fan and full-fan modes. In HCT and ACT, the apparent length of the markers increased or decreased non-linearly with motion parameters and speed of the imaging couch. When the marker moved opposed to couch motion the apparent lengths decreased, while they increased when the phantom moved along the direction of the imaging couch as predicted by the motion model. The position of marker centers did not shift and distance between makers did not change in CBCT images. However, in HCT and ACT, the position of marker center and distance between markers varied depending on motion parameters during imaging. The marker center could move superiorly or inferiorly and the distance between markers could increase or decrease depending on the phase of motion as predicted by the motion model. CONCLUSIONS: The variations of marker length and position due to phantom motion were quantified by measurement and modeling. These variations may lead to large positioning uncertainties in patient setup and tumor localization based on IGRT with fiducial marker registration. PMID- 27250885 TI - Effect of Fractionated Dose of Radiotherapy on Oral Mucosa in Head and Neck Cancer Patients: A Cytological Assessment. AB - BACKGROUND: Cancer therapy couples with it a plethora of complications of short and long term effects which can be so distressing that patient may tolerate only lower less-effective doses of therapy, may postpone treatments or will discontinue treatment entirely. Fractionated dose of radiotherapy coupled with therapy induce local or systemic infections due to high cellular turnover rates of the oral mucosa, diverse and complex microflora and trauma to oral tissues. Several mucosal abnormalities often results in epithelial and glandular destruction and inflammation, which can be so devastating that it may cause atypical changes on the area exposed to radiation. Thus, the aim of this study was to investigate the feasibility of using cytological evaluation to detect oral epithelial atypia among Head and Neck cancer patients receiving fractionated dose of radiotherapy. METHODS: Study was conducted on 125 head and neck cancer patients receiving radiotherapy. Subjects were divided into 5 study groups on the basis of fractionated dose of radiotherapy from 10th-50th fractions respectively. Mucosal changes were evaluated by exfoliative cytology and atypical changes and inflammatory cell infiltration were assessed. RESULTS: Without prior knowledge of the subjects' group, oral epithelial atypia was detected with increase fractionated dose of radiation. Dense inflammatory nfiltrate were identified in nearly all study groups irrespective of dose of radiotherapy. CONCLUSION: Cytological atypia and inflammatory infiltrates were detected after exposure to radiotherapy. PMID- 27250886 TI - Change in the Quality of Life in Oropharyngeal, Laryngeal and Hypopharyngeal Cancer Patients treated with Volumetric Modulated Arc-Based Concomitant Boost Radiotherapy. AB - OBJECTIVE: To assess the change in the quality of life (QOL) in Oropharyngeal, Laryngeal and Hypopharyngeal cancer patients treated with concomitant boost radiotherapy by Volumetric Intensity Modulated Arc Therapy (VMAT) technique. METHODS: Thirty patients with oropharynx, larynx or hypopharynx cancers of stage II to IVA were treated with an Accelerated fractionation schedule using Concomitant boost. The dose given was 1.8Gy/fraction daily, 5 days a week to the large field for 28 fractions and a daily concomitant boost of 1.5Gy/fraction to the boost field over the last 12 treatment days for a total dose of 68.4Gy/40 fractions/51/2weeks by VMAT technique with concurrent chemotherapy (in stage III and IV patients) using Cisplatin 100mg/m2 IV three weekly during week 1 and week 4 of irradiation. QOL was assessed using the European Organization of Research and Treatment of Cancer Quality of Life Core Questionnaire, version 3.0 (EORTC QLQC30) and EORTC head and neck module (EORTC QLQ-HN35) before treatment, at the end of treatment, 1 month, 3 months and 6 months post treatment. The QOL scores and their evolution over the five measurements were calculated. RESULTS: The change in the QOL scores was acceptable in general. There was a significant reduction in quality of life scores at the end of treatment. The QOL improved in the followup period; and by 3 months post irradiation, there was a return of QOL scores to the baseline value. CONCLUSION: The QOL scores indicate that concomitant boost radiotherapy by VMAT is well tolerated and helps in rapid return to baseline quality of life scores. We believe that this is one of the first papers which have combined concomitant boost radiotherapy with VMAT technique in head and neck cancers. VMAT based concomitant boost radiotherapy helps in rapid return to baseline quality of life. PMID- 27250887 TI - Prostate biopsy handling: special tiss1ue embedding technique with sponges affects the yield of prostatic tissue available for microscopic examination. AB - Prostate cancer is considered as the second most frequently diagnosed malignancy and the sixth leading cause of cancer death in males. The quality of the prostate biopsy and its processing techniques may influence the outcome of the histopathological assessment which is the gold standard for cancer diagnosis. An audit of 240 prostate biopsies from 20 patients was conducted to compare the quality and length of tissue before and after the implementation of sponge embedding technique. The average length of prostatic biopsy before the procedure was 5.8 mm (range 1-15 mm) and the average length after implementation of the procedure was 9.5 mm (range 2-17 mm). This equates to a total of 60% increase in tissue volume after implementation of sponge embedding. A simple modification in the embedding of prostate biopsy in the laboratory resulted in higher quality biopsies available for histopathological examination. PMID- 27250888 TI - Expression of VEGF-A in Epithelial Ovarian Cancer: Correlation with Morphologic Types, Grade and Clinical Stage. AB - AIM: The objective of this study was to evaluate the expression pattern of vascular endothelial growth factor A (VEGF A) in epithelial ovarian cancers (EOC) and to correlate the intensity of expression with morphologic types, histologic grade and clinical stage of the disease. METHODS: Tissue microarrays were constructed from paraffin blocks of 78 cases of EOC in duplicate. Immunohistochemical staining for VEGF A was carried out with mouse monoclonal antibody and the intensity was scored independently by two pathologists (CSP and MA). RESULTS: Twenty six of 78 (33.3%) cases of primary malignant epithelial ovarian neoplasm showed high VEGF A expression. Among high expressors, 23 were seen in serous carcinomas, two in undifferentiated carcinomas and one in mixed carcinoma. High expression was not seen in other types like, endometrioid, mucinous and clear cell carcinomas. High VEGF-A expression was also associated high grade and advanced stage of the disease. CONCLUSION: High VEGF-A expression in epithelial ovarian cancer was found to be associated with serous morphology, high grade and advanced stage of the disease. Though some degree of VEGF A expression was seen in most ovarian carcinomas, high expression was seen in only one third of cases and this may help in selecting the patients for targeted therapy with antiangiogenic agents. PMID- 27250889 TI - Efficacy of Different Protocols in Treatment of Nephroblastoma: A revisit. AB - BACKGROUND: Management of Nephroblastoma (NB) remains a subject of debate despite the fact that it ranked first among primary childhood's renal neoplasm. We have previously discussed this issue 13, 14, yet, the sample size was limited. AIM: The aim of this study was to further evaluate the efficacy of initial surgery in the treatment of stage II and III pediatric NB as a part of the short administration schedule as in National Wilms' Tumor Study (NWTS)-4 and to evaluate its effectiveness compared to the long administration schedule. PATIENTS AND METHODS: The study included 50 children who were primarily diagnosed as stage II and III NB. They were divided into 2 equal groups. Group I (n = 25) included children who have undergone neoadjuvant chemotherapy followed by surgery and postoperative chemotherapy, while group II (n = 25) included children who have undergone primary surgery as an initial management followed by chemotherapy. After a mean postoperative follow-up period of 20+/-6 months, clinical and radiological evaluation was performed to all patients. RESULTS: In group I, 15 patients were preoperatively diagnosed as stage II and 10 patients as stage III while in group II, 16 patients were proved to be stage II and 9 patients were stage III. After a follow up period, clinical and radiological evaluation using CT was performed to all patients. In patients with stage II, evidence of recurrence was noted in 5 patients of group I whereas no patient showed any evidence of recurrence in group II. In patients with stage III, rebound increase in size was seen in 3 patients in group I and only one patient in group II. CONCLUSIONS: This study confirmed our previous conclusions that initial surgical intervention with appropriate adjuvant therapy has a better outcome than the neoadjuvant chemotherapy and delayed surgery for children primarily diagnosed as stage II and III NB. Moreover, it may also act as a short administration schedule for the treatment as it is not less effective than the long administration schedule and can be administered at a substantially lower total treatment cost. PMID- 27250890 TI - Ectopic Intrathymic Parathyroid adenoma demonstrated on Tc-99m Sestamibi SPECT CT. AB - Intrathymic parathyroid adenoma is a rare cause of primary hyperparathyroidism. In this case, Tc-99m Sestamibi SPECT-CT successfully localized abnormal tracer uptake in the mediastinum with corresponding low density lesion on CT images suggestive of mediastinal parathyroid adenoma which late on confirmed on histopathology. After the median sternotomy a large intrathymic parathyroid adenoma was identified and excised. With the help of gamma probe the surgeons detect the lesion early and with more confidence as well as reducing the total operation time. Tc-99m Sestamibi SPECT-CT scintigraphy and gamma probe localization is recommended for preoperative and intra operative localization of ectopic parathyroid adenomas. PMID- 27250891 TI - Is cutaneous leishmaniasis a risk factor for basal cell carcinoma? AB - BACKGROUND: Basal cell carcinoma (BCC) is the most common epithelial neoplasm of skin. Risk factors for the development of BCC include intermittent intense sun exposure, radiation therapy, family history of BCC, immune suppression and fair complexion, especially red hair. It can originate in scars like small pox, vaccination, chicken pox or surgical scars. OBJECTIVE AND CONCLUSION: We present a case of basal cell carcinoma arising in a leishmania scar on the nose, sixty years after the primary lesion. Although rare, BCC's have arisen in leishmania scars. Thus the possibility of basal cell carcinoma should be considered while dealing with such patients. Even though a causal relationship, if any, cannot be ascertained at present. PMID- 27250892 TI - Bilateral Choroidal Metastases from Prostate Cancer revealed in a patient under Abiraterone - Fourteen years after diagnosis. AB - Choroidal metastasis from prostate cancer is very rare and usually presents late during the disease. Since 2010, many new drugs were approved in the treatment of castrationresistant prostate cancer, including Abiraterone acetate. We report a case of bilateral choroidal metastases from prostate cancer 3 months after the initiation of Abiraterone. Abiraterone was not efficient in controlling the progression of the disease in this case, especially the choroidal metastasis. More case reports are essential in order to evaluate the role of Abiraterone in controlling choroidal metastases from prostate adenocarcinoma. PMID- 27250893 TI - Spectrum of Presentation of Anorectal Malignant Melanoma: Experience of a Tertiary Care Centre of North India. AB - Malignant melanoma of the anorectum is a rare but highly aggressive tumor. We report our experience of anorectal melanoma in five patients. Of these, two have advanced disease, two had localized disease and one patient had florid systemic metastases with a history of hemorrhoidectomy one year prior. One patient whose metastatic workup was negative, expired on post-op day 15 of abdominoperineal resection due to unsuspected but florid cerebral metastases. Another patient with localized disease underwent an APR with curative resection and post-op whole body PET scan negative for occult or residual disease. Advanced stage patients were referred for chemotherapy. To improve prognosis, it is important to detect anorectal melanoma at an early stage. PMID- 27250894 TI - Metaplastic carcinoma of breast: A case series of seven patients from a tertiary care center and review of literature. AB - PURPOSE: Metaplastic carcinoma of breast (MCB) is a rare histological subtype of breast carcinoma and accounts for less than 1 percent of the total breast cancer cases. Here we are reporting a series of seven patients of MCB from single institute along with review of literature. MATERIAL AND METHODS: Patients records from January 2008 to August 2014 were retrieved to search for MCB patients. A etrospective review was conducted to document the clinicopathological features, treatment and outcomes of these patients. The data was entered in a predesigned proforma document. RESULTS: Seven patients were diagnosed to have MCB during this period. Most common symptom at presentation was lump in the breast with associated discharge per nipple in one patient. On histology, there was no definite differentiation in four patients while one patient had spindle cell neoplasia, one had osteoid and chondroid neoplasia respectively. Five patients underwent modified radical mastectomy while other two patients underwent simple mastectomy. All the patients were pathologically node negative and triple negative breast cancer. Adjuvant chemo-radiotherapy was given to all patients. Median follow up was 4 years (Range 3-6 years). Three out of seven patients completed 5 years of follow up. One patient developed isolated liver metastasis six years after completion of the treatment and she lost to follow up for further treatment. CONCLUSION: Metaplastic carcinoma of breast is a rare disease entity and there are no specific treatment guidelines. The prognosis of patients in this rare sub group remains poor and multi institutional studies evaluating role of new therapies may be required to improve outcome. PMID- 27250895 TI - DNA methylation and Cancer: Identifying and targeting epigenetic modifications may be the future of cancer therapy? AB - DNA methylation has been recognized as one of the most important epigenetic mechanisms regulating the expression and inhibition of genes giving rise to an organism's phenotype. It is hence of no surprise that when DNA methylation mechanisms are disrupted by intrinsic or extrinsic causes, the likelihood of tumourigenesis increases. Both hypermethylation and hypomethylation may predispose to cancer formation through aberrant inhibition or expression of particular genes and this is seen in different types of cancers, such as laryngeal squamous cell carcinoma and acute myeloid leukaemia. By increasing our knowledge and understanding of these epigenetic mechanisms, we will be able to develop diagnostic techniques such as methylation profiling, to screen for and detect aberrant methylation patterns which may predispose to cancer formation in our patients. This would enable early diagnosis and treatment which may also involve the use of drugs developed to provide directed epigenetic therapy, shifting away from the current trend which involves the use of radical anti cancer therapy. These diagnostic and treatment options may be the future of cancer management. PMID- 27250896 TI - Novel agents in second-line therapy for EGFR wild-type Advanced Non-Small-Cell Lung Cancer. AB - Lung cancer is the leading cause of cancer-related mortality worldwide owing to its advanced-stage at the time of diagnosis. The majority of patients will require a second-line therapy after progression during first-line treatment. While treatment for NSCLC with EGFR mutation or EML4/ALK fusion, target therapy is the favored second-line therapy if not already used in first-line therapy, NSCLC with EGFR wild-type remains an unmet need and many oncologists favor cytotoxic therapy. Recently, a better understanding of lung cancer biology, with a better selection of patients based on histology, molecular biology and the identification of potential target antigens in the immune system have significantly improved patient outcome. This article will provide an update on different treatment options available for patients with EGFR wild-type advanced NSCLC who relapse after first-line therapy, which includes essentially ramucirumab, vandetanib, nivolumab, and pembrolizumab and considerations that may allow clinicians to a better choice of agent for second-line therapy. PMID- 27250897 TI - 3D-printed bioanalytical devices. AB - While 3D printing technologies first appeared in the 1980s, prohibitive costs, limited materials, and the relatively small number of commercially available printers confined applications mainly to prototyping for manufacturing purposes. As technologies, printer cost, materials, and accessibility continue to improve, 3D printing has found widespread implementation in research and development in many disciplines due to ease-of-use and relatively fast design-to-object workflow. Several 3D printing techniques have been used to prepare devices such as milli- and microfluidic flow cells for analyses of cells and biomolecules as well as interfaces that enable bioanalytical measurements using cellphones. This review focuses on preparation and applications of 3D-printed bioanalytical devices. PMID- 27250898 TI - An Application of Item Response Theory and the Rasch Model in Speech Recognition Test Materials. AB - PURPOSE: The purpose of this study was to describe an attempt to apply item response theory (IRT) and the Rasch model to construction of speech-recognition tests. A set of word-recognition test items applicable to children as young as 3 years old-with any level of hearing sensitivity, with or without using hearing devices-was developed. METHOD: Test items were constructed through expert consultation and by reference to some established language corpora, validated with 121 participants with various degrees of hearing loss and 255 with typical hearing. IRT and the Rasch model were applied to evaluate item quality. RESULTS: Eighty disyllabic word items were selected in accordance with IRT. The speech recognition abilities of the 376 young participants are reported. The IRT analyses on this set of data are also discussed. CONCLUSIONS: A new set of speech recognition test materials in Cantonese Chinese has been developed. Construction of short equivalent lists may be performed in accordance with IRT item qualities. Clinical applications of this test tool in the particular language population are discussed. PMID- 27250899 TI - Arterial Stiffness Measured with the Cuff Oscillometric Method Is Predictive of Exercise Capacity in Patients with Cardiac Diseases. AB - Arterial stiffness is widely used in assessing arteriosclerosis in the background of increased cardiovascular events. Arteriosclerosis also causes reduction in exercise capacity, which is a most important prognostic factor in patients with cardiovascular disease; however, data on the association between arterial stiffness and exercise capacity are limited. Therefore, a simple and noninvasive measurement of arterial stiffness that reflects the central circulation and exercise capacity is needed. The arterial velocity pulse index (AVI) is a parameter of arterial stiffness measurable with the cuff oscillometric method; however, the clinical utility of this method is unclear. We aimed to evaluate the trend of AVI in patients with coronary artery disease (CAD), and the association between AVI and exercise capacity. A cross-sectional study of 116 patients with cardiac disease (34 CAD and 82 non-CAD patients) was performed. Non-CAD patients were those with any cardiac diseases who did not have proven CAD. The results showed that the AVI was significantly higher in CAD patients than non-CAD patients (P < 0.05, analysis of covariance). The AVI was inversely correlated with peakVO2 (r = -0.239, P < 0.05) and was a significant explanatory variable for peakVO2 in stepwise regression analysis (beta = -14.62, t = -2.5, P < 0.05). These results indicate that the AVI is strongly associated with CAD and predictive of the exercise capacity in patients with cardiac diseases. We, therefore, propose that the cuff oscillometric method is clinically useful in evaluating arterial stiffness in patients with cardiac diseases, especially CAD. PMID- 27250900 TI - Perinatal Coxsackievirus B3 Infection with Transient Thrombocytopenia. AB - Coxsackievirus (Cox) B is the second common picornaviruses, after echovirus, detected from children younger than 2 months of age. Neonates who present with Cox B3 infection in the first week are known to have severe illness such as myocarditis or menigoencephalitis. Severity is commonly associated with perinatal vertical transmission. Here, we report a neonatal case of Cox B3 infection with severe thrombocytopenia through horizontal transmission. The patient was a preterm infant born without asphyxia by selective cesarean section. From his 6(th) day of life, the patient had recurrent episodes of apnea. At that time, the laboratory investigations revealed a profound thrombocytopenia without any evidence of inflammation. Thus, neonatal alloimmune thrombocytopenia (NAIT) was suspected, and the patient received transfusion of immunoglobulin and platelets. Thereafter, the patient had no further episodes of apnea, and platelet counts of the patient increased gradually. Later, the possibility of NAIT was ruled out by the result of the platelet antigen genotyping of the patient and his parents. Culture obtained from his nasopharynx was positive for Cox B3. We thus speculate that the patient was exposed to the virus from his mother because she had a febrile episode at her 5(th) day after delivery, and her Cox B3 infection was confirmed by serology. Assuming that the thrombocytopenia was a complication of Cox B3 infection, the immunoglobulin transfusion might have provided a neutralizing antibody against Cox B3. It is important to consider the possibility of enterovirus infection as a differential diagnosis whenever unexplained thrombocytopenia was observed in neonates. PMID- 27250901 TI - Intracellular quantitative detection of human thymidylate synthase engagement with an unconventional inhibitor using tetracysteine-diarsenical-probe technology. AB - Demonstrating a candidate drug's interaction with its target protein in live cells is of pivotal relevance to the successful outcome of the drug discovery process. Although thymidylate synthase (hTS) is an important anticancer target protein, the efficacy of the few anti-hTS drugs currently used in clinical practice is limited by the development of resistance. Hence, there is an intense search for new, unconventional anti-hTS drugs; there are approximately 1600 ongoing clinical trials involving hTS-targeting drugs, both alone and in combination protocols. We recently discovered new, unconventional peptidic inhibitors of hTS that are active against cancer cells and do not result in the overexpression of hTS, which is a known molecular source of resistance. Here, we propose an adaptation of the recently proposed tetracysteine-arsenic-binding motif technology to detect and quantitatively characterize the engagement of hTS with one such peptidic inhibitor in cell lysates. This new model can be developed into a test for high-throughput screening studies of intracellular target protein/small-molecule binding. PMID- 27250903 TI - Microfluidic enzymatic DNA extraction on a hybrid polyester-toner-PMMA device. AB - To date, the forensic community regards solid phase extraction (SPE) as the most effective methodology for the purification of DNA for use in short tandem repeat (STR) polymerase chain reaction (PCR) amplification. While a dominant methodology, SPE protocols generally necessitate the use of PCR inhibitors (guanidine, IPA) and, in addition, can demand timescales of up to 30 min due to the necessary load, wash and elution steps. The recent discovery and characterization of the EA1 protease has allowed the user to enzymatically extract (not purify) DNA, dramatically simplifying the task of producing a PCR ready template. Despite this, this procedure has yet to make a significant impact on microfluidic technologies. Here, we describe a microfluidic device that implements the EA1 enzyme for DNA extraction by incorporating it into a hybrid microdevice comprising laminated polyester (Pe) and PMMA layers. The PMMA layer provides a macro-to-micro interface for introducing the biological sample into the microfluidic architecture, whilst also possessing the necessary dimensions to function as the swab acceptor. Pre-loaded reagents are then introduced to the swab chamber centrifugally, initiating DNA extraction at 75 degrees C. The extraction of DNA occurs in timescales of less than 3 min and any external hardware associated with the transportation of reagents by pneumatic pumping is eliminated. Finally, multiplexing is demonstrated with a circular device containing eight separate chambers for the simultaneous processing of eight buccal swab samples. The studies here provide DNA concentrations up to 10 ng MUL( 1) with a 100% success rate in less than 3 minutes. The STR profiles generated using these extracted samples demonstrate that the DNA is of PCR forensic-quality and adequate for human identification. PMID- 27250904 TI - Neighborhood Collective Efficacy Moderates the Association between Maternal Adverse Childhood Experiences and Marital Conflict. AB - In a socio-demographically diverse sample of 501 caregivers participating in a longitudinal birth cohort study during the childbearing years, we examined whether neighborhood collective efficacy moderated the association between maternal adverse childhood experience (ACEs) and marital conflict. Maternal ACEs were assessed via retrospective reports. Neighborhood collective efficacy was measured via maternal and paternal reports at 2 months, and maternal reports of marital conflict were collected at infant age 2 and 18 months. Multiple linear regression analyses revealed that maternal ACEs were associated with increased marital conflict. Neighborhood collective efficacy moderated the association between early maternal ACEs and marital conflict, such that mothers experiencing ACEs had lower levels of marital conflict when exposed to high levels of neighborhood collective efficacy. Results suggest that extra-familial sources of social support and control, such as feelings of security, trust, order, and connectedness with others, may buffer the effects of early adversity on marital discord. PMID- 27250905 TI - Short Communication: Few Liver-Infiltrating Cells Express CXCR3 in HIV/HCV Patients Commencing Antiretroviral Therapy. AB - Coinfections with Hepatitis C virus and human immunodeficiency virus accelerate the progression of both conditions and hamper effective treatment. Here we describe expression of CXCR3 on liver-infiltrating cells and peripheral T cells from coinfected patients commencing antiretroviral therapy (ART) in Indonesia. CXCR3 was expressed by small number of intrahepatic inflammatory cells, mostly in the portal areas. The number of cells did not change on ART and was markedly lower than the number of CD4+ and CD8+ cells in the liver. Data suggest that CXCR3 may contribute to liver infiltration but demonstrate a dynamic situation, changing as the immune system recovers on ART. PMID- 27250906 TI - State-of-the art advances in fertility preservation for the male cancer patient. PMID- 27250907 TI - Exploiting the sigma-phylic properties of cationic gold(i) catalysts in the ring opening reactions of aziridines with indoles. AB - A study on the SN2-type ring opening reactions of aziridines with indoles as nucleophiles is reported. Under gold(i) catalysis a great variety of tryptamine derivatives were prepared in good to excellent yields with complete stereocontrol when chiral aziridines were used. We demonstrated that cationic gold(i) catalysts are superior Lewis acids to the previously reported group 3, 12 and 13 metals in terms of catalyst loading and reaction yields. Moreover, complete regioselectivity was observed for 2-phenyl-N-tosylaziridine; whereas, regioselectivity up to 10 : 1 ratio was observed with 2-methyl-N-tosylaziridine. Finally, a preliminary study on the dearomatization reactions giving rise to pyrroloindolines is also reported. PMID- 27250909 TI - Arousal dynamics drive vocal production in marmoset monkeys. AB - Vocal production is the result of interacting cognitive and autonomic processes. Despite claims that changes in one interoceptive state (arousal) govern primate vocalizations, we know very little about how it influences their likelihood and timing. In this study we investigated the role of arousal during naturally occurring vocal production in marmoset monkeys. Throughout each session, naturally occurring contact calls are produced more quickly, and with greater probability, during higher levels of arousal, as measured by heart rate. On average, we observed a steady increase in heart rate 23 s before the production of a call. Following call production, there is a sharp and steep cardiac deceleration lasting ~8 s. The dynamics of cardiac fluctuations around a vocalization cannot be completely predicted by the animal's respiration or movement. Moreover, the timing of vocal production was tightly correlated to the phase of a 0.1-Hz autonomic nervous system rhythm known as the Mayer wave. Finally, a compilation of the state space of arousal dynamics during vocalization illustrated that perturbations to the resting state space increase the likelihood of a call occurring. Together, these data suggest that arousal dynamics are critical for spontaneous primate vocal production, not only as a robust predictor of the likelihood of vocal onset but also as scaffolding on which behavior can unfold. PMID- 27250910 TI - Current advances in invertebrate vision: insights from patch-clamp studies of photoreceptors in apposition eyes. AB - Traditional electrophysiological research on invertebrate photoreceptors has been conducted in vivo, using intracellular recordings from intact compound eyes. The only exception used to be Drosophila melanogaster, which was exhaustively studied by both intracellular recording and patch-clamp methods. Recently, several patch clamp studies have provided new information on the biophysical properties of photoreceptors of diverse insect species, having both apposition and neural superposition eyes, in the contexts of visual ecology, behavior, and ontogenesis. Here, I discuss these and other relevant results, emphasizing differences between fruit flies and other species, between photoreceptors of diurnal and nocturnal insects, properties of distinct functional types of photoreceptors, postembryonic developmental changes, and relationships between voltage-gated potassium channels and visual ecology. PMID- 27250911 TI - Beyond cones: an improved model of whisker bending based on measured mechanics and tapering. AB - The sense of touch is represented by neural activity patterns evoked by mechanosensory input forces. The rodent whisker system is exceptional for studying the neurophysiology of touch in part because these forces can be precisely computed from video of whisker deformation. We evaluate the accuracy of a standard model of whisker bending, which assumes quasi-static dynamics and a linearly tapered conical profile, using controlled whisker deflections. We find significant discrepancies between model and experiment: real whiskers bend more than predicted upon contact at locations in the middle of the whisker and less at distal locations. Thus whiskers behave as if their stiffness near the base and near the tip is larger than expected for a homogeneous cone. We assess whether contact direction, friction, inhomogeneous elasticity, whisker orientation, or nonconical shape could explain these deviations. We show that a thin-middle taper of mouse whisker shape accounts for the majority of this behavior. This taper is conserved across rows and columns of the whisker array. The taper has a large effect on the touch-evoked forces and the ease with which whiskers slip past objects, which are key drivers of neural activity in tactile object localization and identification. This holds for orientations with intrinsic whisker curvature pointed toward, away from, or down from objects, validating two-dimensional models of simple whisker-object interactions. The precision of computational models relating sensory input forces to neural activity patterns can be quantitatively enhanced by taking thin-middle taper into account with a simple corrective function that we provide. PMID- 27250913 TI - Management of patients treated with pertuzumab in the Australian clinical practice setting. AB - AIM: Treatment with pertuzumab-trastuzumab-taxane combinations has become the international standard of care for patients with HER2-positive metastatic breast cancer. In this paper we discuss the practicalities of treating patients with this combination with a particular focus on treatment in the Australian setting. METHOD: An expert panel was convened to discuss practical aspects for use of pertuzumab in the Australian clinical setting. The findings of this panel are reported in this article. RESULTS: The combination of pertuzumab-trastuzumab docetaxel has established efficacy in patients with HER2-positive metastatic breast cancer, prolonging progression-free and overall survival compared to trastuzumab-taxane combinations. In Australia, combinations of pertuzumab and trastuzumab with docetaxel or paclitaxel are reimbursed. Management of treatment related side-effects such as diarrhea, febrile neutropenia and neuropathy typically include dose reduction or switching taxane. Specific patients with poorer tolerance of chemotherapy such as the elderly or those from Asian backgrounds may require particular management strategies. CONCLUSIONS: The advent of targeted therapies for women with metastatic HER2-positive breast cancer has markedly improved survival. Combinations of pertuzumab-trastuzumab and a taxane are the standard of care in patients with good performance status. Given prolongation of survival and the importance of quality of life endpoints, the treatment paradigm for patients with metastatic HER2-positive breast cancer is changing rapidly. Careful management of toxicities is required, and dose reduction or switching taxane may be necessary. Further research is required on the efficacy of pertuzumab combinations in patients with brain metastases, and on those who relapse quickly following adjuvant therapy. PMID- 27250912 TI - Feature-based attention and spatial selection in frontal eye fields during natural scene search. AB - When we search for visual objects, the features of those objects bias our attention across the visual landscape (feature-based attention). The brain uses these top-down cues to select eye movement targets (spatial selection). The frontal eye field (FEF) is a prefrontal brain region implicated in selecting eye movements and is thought to reflect feature-based attention and spatial selection. Here, we study how FEF facilitates attention and selection in complex natural scenes. We ask whether FEF neurons facilitate feature-based attention by representing search-relevant visual features or whether they are primarily involved in selecting eye movement targets in space. We show that search-relevant visual features are weakly predictive of gaze in natural scenes and additionally have no significant influence on FEF activity. Instead, FEF activity appears to primarily correlate with the direction of the upcoming eye movement. Our result demonstrates a concrete need for better models of natural scene search and suggests that FEF activity during natural scene search is explained primarily by spatial selection. PMID- 27250914 TI - Before-after environmental impact assessment of an artificial channel opening on a south-western Atlantic choked lagoon system. AB - This study aimed to evaluate the human induced impact of a channel opening in a choked lagoon and attempted to establish the cause-effect links for the observed changes. The same lagoon system was sampled before and after the channel opening event, and the differences in fish and crustacean assemblages and environmental variables between these periods analysed. The opening of the artificial channel resulted in salinity increases, leading to a shift in species composition, favouring marine species and reducing abundance and diversity of previously dominant freshwater species. Furthermore, saltwater entrance into the choked lagoon caused an unexpected decrease in species richness and biomass, plus deterioration of ecosystem processes, reducing fishing capacity. The effects of salinity on the ecosystem vary depending on the ecosystem's composition and capacity to overcome salinity changes, thus specific monitoring projects are important strategies for developing coastal lagoon conservation management. PMID- 27250915 TI - Effect of multilayer structure, stacking order and external electric field on the electrical properties of few-layer boron-phosphide. AB - Development of nanoelectronics requires two-dimensional (2D) systems with both direct-bandgap and tunable electronic properties as they act in response to the external electric field (E-field). Here, we present a detailed theoretical investigation to predict the effect of atomic structure, stacking order and external electric field on the electrical properties of few-layer boron-phosphide (BP). We demonstrate that the splitting of bands and bandgap of BP depends on the number of layers and the stacking order. The values for the bandgap show a monotonically decreasing relationship with increasing layer number. We also show that AB-stacking BP has a direct-bandgap, while ABA-stacking BP has an indirect bandgap when the number of layers n > 2. In addition, for a bilayer and a trilayer, the bandgap increases (decreases) as the electric field increases along the positive direction of the external electric field (E-field) (negative direction). In the case of four-layer BP, the bandgap exhibits a nonlinearly decreasing behavior as the increase in the electric field is independent of the electric field direction. The tunable mechanism of the bandgap can be attributed to a giant Stark effect. Interestingly, the investigation also shows that a semiconductor-to-metal transition may occur for the four-layer case or more layers beyond the critical electric field. Our findings may inspire more efforts in fabricating new nanoelectronics devices based on few-layer BP. PMID- 27250916 TI - How well are health information websites displayed on mobile phones? Implications for the readability of health information. AB - Issue addressed More than 87% of Australians own a mobile phone with Internet access and 82% of phone owners use their smartphones to search for health information, indicating that mobile phones may be a powerful tool for building health literacy. Yet, online health information has been found to be above the reading ability of the general population. As reading on a smaller screen may further complicate the readability of information, this study aimed to examine how health information is displayed on mobile phones and its implications for readability. Methods Using a cross-sectional design with convenience sampling, a sample of 270 mobile webpages with information on 12 common health conditions was generated for analysis, they were categorised based on design and position of information display. Results The results showed that 71.48% of webpages were mobile-friendly but only 15.93% were mobile-friendly webpages designed in a way to optimise readability, with a paging format and queried information displayed for immediate viewing. Conclusion With inadequate evidence and lack of consensus on how webpage design can best promote reading and comprehension, it is difficult to draw a conclusion on the effect of current mobile health information presentation on readability. So what? Building mobile-responsive websites should be a priority for health information providers and policy-makers. Research efforts are urgently required to identify how best to enhance readability of mobile health information and fully capture the capabilities of mobile phones as a useful device to increase health literacy. PMID- 27250917 TI - Time to Reperfusion in ST-Segment Elevation Myocardial Infarction Patients With vs. Without Pre-Hospital Mobile Telemedicine 12-Lead Electrocardiogram Transmission. AB - BACKGROUND: Prehospital ECG improves survival following ST-segment elevation myocardial infarction (STEMI). Although a new International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations placed new emphasis on the role of prehospital ECG, this technology is not widely used in Japan. We developed a mobile telemedicine system (MTS) that continuously transmits real-time 12-lead ECG from ambulances in a prehospital setting. This study was designed to compare reperfusion delay between STEMI patients with different prehospital transfer pathways. METHODS AND RESULTS: Between 2008 and 2012, 393 consecutive STEMI patients were transferred by ambulance to hospital (PCI-capable center); 301 patients who underwent primary percutaneous coronary intervention (PCI) were enrolled prospectively. We compared time to reperfusion between patients transferred to PCI-capable hospital using the MTS (MTS group, n=37), patients directly transferred from the field to PCI capable hospital without the MTS (field transfer group, n=125) and patients referred from a PCI-incapable hospital (interhospital transfer group, n=139). Times to reperfusion in the MTS group were significantly shorter than in the other groups, yielding substantial benefits in patients who arrived at a PCI capable hospital within 6 h after symptom onset. On multivariate analysis, MTS use was an independent predictor of <90-min door-to-device interval (OR, 4.61; P=0.005). CONCLUSIONS: Reperfusion delay was shorter in patients using MTS than in patients without it. (Circ J 2016; 80: 1624-1633). PMID- 27250918 TI - Impacts of Surgically Performed Renal Denervation on the Cardiovascular and Electrophysiological Variables in the Chronic Atrioventricular Block Dogs - Comparison With Those of Amiodarone Treatment. AB - BACKGROUND: In order to begin to precisely clarify the impact of renal denervation on the blood pressure, atrial fibrillation and ventricular tachyarrhythmias, in addition to proarrhythmic potential, its cardiovascular effects were assessed by using the chronic complete atrioventricular block dogs. METHODS AND RESULTS: Cardiohemodynamic and electrophysiological effects, together with neurohumoral factors and/or electrolytes, were assessed before and 4 weeks after either renal denervation (n=5) or amiodarone treatment (n=6). Amiodarone hydrochloride was given orally to the animals every day in a dose of 200 mg/day for the first 7 days followed by 100 mg/day for the following 21 days. The renal denervation decreased the systolic pressure, idioventricular rate, prolonged ventricular effective refractory period, and slightly suppressed the adrenergic tone and the renin-angiotensin-aldosterone system, but hardly affected the atrial effective refractory period and terminal repolarization period. Amiodarone prolonged the atrial effective refractory period, whereas no significant change was detected in the other variables. CONCLUSIONS: Surgically performed renal denervation may possess the anti-ventricular tachyarrhythmic rather than anti atrial fibrillatory potentials, and it also modestly decreased the blood pressure. Thus, currently obtained information may be used as guidance for better understanding the utility and limitation of renal denervation against various types of cardiovascular diseases. (Circ J 2016; 80: 1556-1563). PMID- 27250919 TI - Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity. AB - The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed. PMID- 27250921 TI - Pudendal neuralgia after pelvic surgery using mesh: Case reports and laparoscopic pudendal nerve decompression. AB - Persistent pain after vaginal mesh surgery is a rare and agonizing entity that has devastating consequences for the patient's quality of life. Many etiologies have been blamed including nerve injuries and entrapments. Pudendal neuralgia is a rare chronic neuropathic pain syndrome in the anatomical territory of the pudendal nerve. Various treatment options, such as medication management, physiotherapy, nerve blocks, decompression surgery and neuromodulation, have been used, but the most appropriate treatment for pudendal neuralgia has not yet been determined. In this article, we present two cases of postoperative pelvic pain thought to be secondary to injury or mechanical distortion of the pudendal nerve after rectocele repair using mesh and tension-free vaginal tape sling. In cases of failed conservative treatment and of mesh removal surgery, laparoscopic pudendal nerve decompression and omental flap wrapping operation can be a treatment option for pudendal neuralgia. PMID- 27250920 TI - Role of Histidine 547 of Human Dopamine Transporter in Molecular Interaction with HIV-1 Tat and Dopamine Uptake. AB - HIV-1 Tat plays an important role in HIV-associated neurocognitive disorders (HAND) by disrupting neurotransmission including dopamine uptake by human dopamine transporter (hDAT). Previous studies have demonstrated that HIV-1 Tat directly binds to hDAT and some amino-acid mutations that attenuate the hDAT-Tat binding also significantly decreased dopamine uptake activity of hDAT. This combined computational-experimental study demonstrates that histidine-547 (H547) of hDAT plays a crucial role in the hDAT-Tat binding and dopamine uptake by hDAT, and that the H547A mutation can not only considerably attenuate Tat-induced inhibition of dopamine uptake, but also significantly increase the Vmax of hDAT for dopamine uptake. The finding of such an unusual hDAT mutant capable of both increasing the Vmax of hDAT for dopamine uptake and disrupting the hDAT-Tat binding may provide an exciting knowledge basis for development of novel concepts for therapeutic treatment of the HAND. PMID- 27250923 TI - Computational insights into intriguing vibration-induced pulsing diradical character in perfluoropentacene and the perfluorination effect. AB - As an n-type organic semiconductor compound, perfluoropentacene has more widespread applications in organic electronics because of its higher electron mobility compared with its parent pentacene. Herein, we explore intriguing dynamic electronic properties of perfluoropentacene caused by structural vibrations using density functional theory calculations. Perfluoropentacene could exhibit diradical character because of the persistent vibrations, although it belongs to a closed-shell singlet molecule in its equilibrium configuration. Not all the vibration-induced structural changes can induce diradical character, but only those leading to a small singlet-triplet energy gap, especially the small HOMO-LUMO gap, as well as the short cross-linking C-C bonds and distorted carbon ring structures in polyacetylene chains make great contributions. Due to molecular vibrations, the diradical character of dynamic perfluoropentacene exhibits pulsing behavior. Compared with pentacene, its perfluorination can not only considerably stabilize two frontier molecular orbitals, but also reduce the HOMO-LUMO gap, thus leading to an increase of the number of vibrational modes which can make the diradical character appear. In particular, perfluorination makes 19 diradical vibrational modes appear in the low frequency region. These observations indicate that some low energy pulses can trigger perfluoropentacene molecular vibrations according to some low energy modes and thus the appearance of pulsing diradical character or molecular magnetism. Clearly, the observed novel characters of a molecule possessing hidden pulsing diradical character and tunable magnetism in this work would contribute to opening up promising areas for designing peculiar magnetic materials. PMID- 27250922 TI - CRIPT exonic deletion and a novel missense mutation in a female with short stature, dysmorphic features, microcephaly, and pigmentary abnormalities. AB - Mutations in CRIPT encoding cysteine-rich PDZ domain-binding protein are rare, and to date have been reported in only two patients with autosomal recessive primordial dwarfism and distinctive facies. Here, we describe a female with biallelic mutations in CRIPT presenting with postnatal growth retardation, global developmental delay, and dysmorphic features including frontal bossing, high forehead, and sparse hair and eyebrows. Additional clinical features included high myopia, admixed hyper- and hypopigmented macules primarily on the face, arms, and legs, and syndactyly of 4-5 toes bilaterally. Using whole exome sequencing (WES) and chromosomal microarray analysis (CMA), we detected a c.8G>A (p.C3Y) missense variant in exon 1 of the CRIPT gene inherited from the mother and a 1,331 bp deletion encompassing exon 1, inherited from the father. The c.8G>A (p.C3Y) missense variant in CRIPT was apparently homozygous in the proband due to the exon 1 deletion. Our findings illustrate the clinical utility of combining WES with copy number variant (CNV) analysis to provide a molecular diagnosis to patients with rare Mendelian disorders. Our findings also illustrate the clinical spectrum of CRIPT related mutations. (c) 2016 Wiley Periodicals, Inc. PMID- 27250924 TI - Predictors of clinical outcome in emphysema patients with atelectasis following endoscopic valve therapy: A retrospective study. AB - BACKGROUND AND OBJECTIVE: The aim of endoscopic valve therapy in patients with emphysema is complete lobar atelectasis of the most emphysematous lobe. However, even after the radiological advent of atelectasis, great variability in clinical outcomes can be observed. METHODS: The baseline clinical measures (vital capacity (VC), forced expiratory flow in 1 s (FEV1 ), residual volume (RV) and 6-min walk test (6-MWT)) and computed tomography variables (low attenuation volume (LAV) of the target lobe, LAV% of the target and the ipsilateral untreated lobe and LAV of the target lobe to LAV of the target lung and to LAV of the total lung) of 77 patients with complete atelectasis following valve therapy were retrospectively examined to determine their impact on patient's outcome (changes in VC, FEV1 , RV and 6-MWT from baseline to the time of atelectasis). RESULTS: Low attenuation volume of the target lobe to LAV of the target lung predicts a significant FEV1 improvement in patients with complete lobar atelectasis following valve therapy. A 10% difference in that computed tomography predictor was associated with a 82 mL improvement in FEV1 (P = 0.006). Lower 6-MWT scores, low VC and high RV at baseline were significantly associated with greater improvement in the respective parameter (all P < 0.001). CONCLUSION: Low attenuation volume of the target lobe to LAV of the target lung and baseline clinical measures seem to significantly predict clinical outcomes in patients with complete lobar atelectasis following valve treatment. PMID- 27250925 TI - Cutaneous murine model of infection caused by Neoscytalidium dimidiatum: a preliminary study of an emerging human pathogen. AB - Neoscytalidium dimidiatum is an emerging fungus that causes a skin infection similar to dermatophytosis; it affects both immunocompetent and immunosuppressed individuals, and it may invade deeper tissues and organs and cause systemic disease. Little is known about the etiopathogenesis of the infection caused by this fungus, and no standard effective treatment is available. The aim of the present experimental study was to develop an animal model of skin infection with N. dimidiatum. BALB/c mice were inoculated with two fungal strains, and different routes of infection were tested. When challenged intradermally, N. dimidiatum strain HUPE164165 caused skin infection in 67% of the animals whereas strain HUPE115669 did it in 49%. Neoscytalidium dimidiatum was isolated from the skin of 25% of the animals inoculated via epidermal scarification and from 100% of the animals challenged via subcutaneous injection. Mice inoculated intradermally were followed-up during four weeks, and clinical samples were collected on days 3, 8, 15, and 29 after inoculation, corresponding to different stages of infection. The cutaneous infection rate, as measured by the recovery of N. dimidiatum strain HUPE164165 from skin biopsies of animals inoculated intradermally, revealed the presence of infection in 90% of the animals sacrificed at 3 days post inoculation, 71% at 8, 85% at 15, and 33% at 29. Conidia and hyphae were observed in PAS-stained sections as well as a mild to moderate inflammatory infiltrate in haematoxylin-eosin, although it did not differ from animals inoculated either with T. quinckeanum or PBS. The intradermal route of inoculation was considered to be suitable for the study of skin infection with N. dimidiatum The animal model developed in this preliminary study is the first to allow the study of cutaneous infection with N. dimidiatum and may contribute to further investigations of the aetiology, immunology, pathogenesis and treatment targeting this emerging mycosis. PMID- 27250926 TI - Probiotic yeast Saccharomyces boulardii (nom. nud.) modulates adhesive properties of Candida glabrata. AB - Following the widespread use of immunosuppressive therapy together with broad spectrum antimycotic therapy, the frequency of mucosal and systemic infections caused by the pathogenic yeast Candida glabrata has increased in the past decades. Due to the resistance of C. glabrata to existing azole drugs, it is very important to look for new strategies helping the treatment of such fungal diseases. In this study, we investigated the effect of the probiotic yeast Saccharomyces boulardii (nom. nud.) on C. glabrata adhesion at different temperatures, pH values, and in the presence of fluconazole, itraconazole and amphotericin B. We also studied the adhesion of C. glabrata co-culture with Candida krusei, Saccharomyces cerevisiae, two bacterial probiotics Lactobacillus rhamnosus and Lactobacillus casei The method used to assess adhesion was crystal violet staining. Our results showed that despite the nonadhesiveness of S. boulardii cells, this probiotic significantly affected the adherence ability of C. glabrata This effect was highly dependent on C. glabrata strain and was either antagonistic or synergistic. Regarding the extrinsic factors, temperature did not indicate any significant influence on this S. boulardii modulatory effect, while at high pH and at increased concentrations of antimycotics, S. boulardii did not manage to repress the adhesion of C. glabrata strains. The experiments of C. glabrata co-cultures with other species showed that the adhesiveness of two separate cultures could not be used to predict the adhesiveness of their co culture. PMID- 27250927 TI - Production of an anti-dermatophyte monoclonal antibody and its application: immunochromatographic detection of dermatophytes. AB - Tinea refers to superficial infection with one of three fungal genera Microsporum, Epidermophyton, or Trichophyton-that are collectively known as dermatophytes. These infections are among the most common diseases worldwide and cause chronic morbidity. They are usually diagnosed by direct microscopy and fungal culture, which are burdensome to perform in the clinical setting. To supplement conventional methods, we developed a new method that employs an immunochromatography test for detection of dermatophyte infections. First, anti Trichophyton monoclonal antibodies (mAb) were produced in mice using a Trichophyton allergen solution as an immunogen. The mAb specificity was assessed by immunostaining alcohol fixed slide cultures and formalin fixed paraffin embedded microbial samples. Both alcohol- and formalin-fixed samples of all seven species of Trichophyton tested displayed positive immunostaining. Immunochromatography test strips were created using the anti-Trichophyton mAb. The efficiency of the test strip was assessed in patients diagnosed with tinea unguium and in healthy volunteers. Of the 20 patient nails tested, 19 tested positive and one tested negative, whereas of the 17 volunteer nails, only one tested positive. However, KOH microscopic examination of the volunteer nail that tested positive revealed the existence of Trichophyton hyphae. Although the number of nails assayed was small, since the assay had a sensitivity of 95.0% (19/20) and a specificity of 94.1% (16/17), the obtained results were considered to be promising. Thus, while further investigation with a greater number of samples is necessary, this method could potentially be employed as a new diagnostic tool for Trichophyton in the future. PMID- 27250930 TI - Phase I Testing: 60 Years in the Making. PMID- 27250931 TI - Dose Finding of Small-Molecule Oncology Drugs: Optimization throughout the Development Life Cycle. AB - In the current era of rapid marketing approval for promising new products in oncology, dose finding and optimization for small-molecule oncology drugs occurs throughout the development cycle and into the postmarketing setting. Many trials that support a regulatory application have high rates of dose reductions and discontinuations, which may result in postmarketing requirements (PMR) to study alternate doses or dosing schedules. Kinase inhibitors particularly have been susceptible to this problem, and among the 31 approved drugs of this class, the approvals of eight have included such PMRs and/or commitments. Thus, the current paradigm for dose finding and optimization could be improved. Newer strategies for dose finding rather than traditional 3 + 3 designs should be considered where feasible, and dose optimization should be continued after phase I and throughout development. Such strategies will increase the likelihood of a right dose for the right drug at the time of regulatory approval. Clin Cancer Res; 22(11); 2613-7. (c)2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "NEW APPROACHES FOR OPTIMIZING DOSING OF ANTICANCER AGENTS". PMID- 27250929 TI - Molecular Pathways: Targeting the PI3K Pathway in Cancer-BET Inhibitors to the Rescue. AB - The PI3K signaling pathway is a complex and tightly regulated network that is critical for many physiologic processes, such as cell growth, proliferation, metabolism, and survival. Aberrant activation of this pathway can occur through mutation of almost any of its major nodes and has been implicated in a number of human diseases, including cancer. The high frequency of mutations in this pathway in multiple types of cancer has led to the development of small-molecule inhibitors of PI3K, several of which are currently in clinical trials. However, several feedback mechanisms either within the PI3K pathway or in compensatory pathways can render tumor cells resistant to therapy. Recently, targeting proteins of the bromodomain and extraterminal (BET) family of epigenetic readers of histone acetylation has been shown to effectively block adaptive signaling response of cancer cells to inhibitors of the PI3K pathway, which at least in some cases can restore sensitivity. BET inhibitors also enforce blockade of the MAPK, JAK/STAT, and ER pathways, suggesting they may be a rational combinatorial partner for divergent oncogenic signals that are subject to homeostatic regulation. Here, we review the PI3K pathway as a target for cancer therapy and discuss the potential use of BET inhibition to enhance the clinical efficacy of PI3K inhibitors. Clin Cancer Res; 22(11); 2605-10. (c)2016 AACR. PMID- 27250932 TI - Nonclinical Evaluations of Small-Molecule Oncology Drugs: Integration into Clinical Dose Optimization and Toxicity Management. AB - Multidisciplinary approaches that incorporate nonclinical pharmacologic and toxicologic characterization of small-molecule oncology drugs into clinical development programs may facilitate improved benefit-risk profiles and clinical toxicity management in patients. The performance of the current nonclinical safety-testing scheme was discussed, highlighting current strengths and areas for improvement. While current nonclinical testing appears to predict the clinical outcome where the prevalence of specific adverse effects are high, nonclinical testing becomes less reliable for predicting clinical adverse effects that occur infrequently, as with some kinase inhibitors. Although adverse effects associated with kinase inhibitors can often be predicted on the basis of target biology, drugs can be promiscuous and inhibit targets with poorly defined function and associated risks. Improvements in adverse effect databases and better characterization of the biologic activities of drug targets may enable better use of computational modeling approaches in predicting adverse effects with kinase inhibitors. Assessing safety of a lead candidate in parallel with other drug properties enables incorporation of a molecule's best features during chemical design, eliminates the worst molecules early, and permits timely investigation/characterization of toxicity mechanisms for identified liabilities. A safety lead optimization and candidate identification strategy that reduces intrinsic toxicity and metabolic risk and enhances selectivity can deliver selective kinase inhibitors that demonstrate on-target adverse effects identified nonclinically. Integrating clinical and nonclinical data during drug development can facilitate better identification and management of oncology drugs. Follow-up nonclinical studies may be used to better understand the risks in a given patient population and minimize or manage these risks more appropriately. Clin Cancer Res; 22(11); 2618-22. (c)2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "NEW APPROACHES FOR OPTIMIZING DOSING OF ANTICANCER AGENTS". PMID- 27250934 TI - Lessons Learned: Dose Selection of Small Molecule-Targeted Oncology Drugs. AB - Evaluation of dose plays a critical role in a successful oncology development program. Typically for oncology agents, the first-in-man phase I dose-escalation trials are conducted to determine a maximum tolerated dose (MTD). This MTD is taken forward into subsequent trials to establish the safety and efficacy of the drug product. Although this approach was appropriate historically for cytotoxics, the application of MTD as the recommend phase II dose has been problematic for the newer small molecule-targeted oncology agents. Promising alternative approaches using dose and exposure exploration, including lessons learned from recent targeted oncology agent development and approvals, are summarized and discussed. Clin Cancer Res; 22(11); 2630-8. (c)2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "NEW APPROACHES FOR OPTIMIZING DOSING OF ANTICANCER AGENTS". PMID- 27250933 TI - Rendering the 3 + 3 Design to Rest: More Efficient Approaches to Oncology Dose Finding Trials in the Era of Targeted Therapy. AB - Selection of the maximum tolerated dose (MTD) as the recommended dose for registration trials based on a dose-escalation trial using variations of an MTD/3 + 3 design often occurs in the development of oncology products. The MTD/3 + 3 approach is not optimal and may result in recommended doses that are unacceptably toxic for many patients and in dose reduction/interruptions that might have an impact on effectiveness. Instead of the MTD/3 + 3 approach, the authors recommend an integrated approach. In this approach, typically an adaptive/Bayesian model provides a general framework to incorporate and make decisions for dose escalation based on nonclinical data, such as animal efficacy and toxicity data; clinical data, including pharmacokinetics/pharmacodynamics data; and dose/exposure-response data for efficacy and safety. To improve dose-ranging trials, model-based estimation, rather than hypothesis testing, should be used to maximize and integrate the information gathered across trials and doses. This approach may improve identification of optimal recommended doses, which can then be confirmed in registration trials. Clin Cancer Res; 22(11); 2623-9. (c)2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "NEW APPROACHES FOR OPTIMIZING DOSING OF ANTICANCER AGENTS". PMID- 27250936 TI - Correction: Hydroxychloroquine Inhibits Autophagy to Potentiate Antiestrogen Responsiveness in ER+ Breast Cancer. PMID- 27250935 TI - Voxel Level Radiologic-Pathologic Validation of Restriction Spectrum Imaging Cellularity Index with Gleason Grade in Prostate Cancer. AB - PURPOSE: Restriction spectrum imaging (RSI-MRI), an advanced diffusion imaging technique, can potentially circumvent current limitations in tumor conspicuity, in vivo characterization, and location demonstrated by multiparametric magnetic resonance imaging (MP-MRI) techniques in prostate cancer detection. Prior reports show that the quantitative signal derived from RSI-MRI, the cellularity index, is associated with aggressive prostate cancer as measured by Gleason grade (GG). We evaluated the reliability of RSI-MRI to predict variance with GG at the voxel level within clinically demarcated prostate cancer regions. EXPERIMENTAL DESIGN: Ten cases were processed using whole mount sectioning after radical prostatectomy. Regions of tumor were identified by an uropathologist. Stained prostate sections were scanned at high resolution (75 MUm/pixel). A grid of tiles corresponding to voxel dimensions was graded using the GG system. RSI-MRI cellularity index was calculated from presurgical prostate MR scans and presented as normalized z-score maps. In total, 2,795 tiles were analyzed and compared with RSI-MRI cellularity. RESULTS: RSI-MRI cellularity index was found to distinguish between prostate cancer and benign tumor (t = 25.48, P < 0.00001). Significant differences were also found between benign tissue and prostate cancer classified as low-grade (GG = 3; t = 11.56, P < 0.001) or high-grade (GG >= 4; t = 24.03, P < 0.001). Furthermore, RSI-MRI differentiated between low and high-grade prostate cancer (t = 3.23; P = 0.003). CONCLUSIONS: Building on our previous findings of correlation between GG and the RSI-MRI among whole tumors, our current study reveals a similar correlation at voxel resolution within tumors. Because it can detect variations in tumor grade with voxel-level precision, RSI-MRI may become an option for planning targeted procedures where identifying the area with the most aggressive disease is important. Clin Cancer Res; 22(11); 2668-74. (c)2016 AACR. PMID- 27250938 TI - Population Screening for Hemoglobinopathy Profiling: Is the Development of a Microarray Worthwhile? AB - In order to perform affordable and expedient whole population scans for the single nucleotide polymorphisms (SNPs) involved in hemoglobinopathies, microarrays based on single nucleotide extension (SNE) might prove advantageous to whole genome/exome sequencing in terms of cost, speed, interpretation and discretion as they focus on a very small part of the tested genome. The development of a microarray assay entails most of the cost, to be deferred by the massive use of the end product. A microarray assay development project, involving multiplex polymerase chain reaction (PCR), labeling, hybridization and scanning/scoring steps is presented as a paradigm of objective bug ratios expected to such procedures and of ways to cope with them. Qualification of the microarray genotypes needs a reference method, which may still be restriction digestion or other, as sequencing remains an expensive commodity. Optimization of wet steps should also be followed by careful and perhaps individualized dye excitation and in silico scoring rules, taking into consideration decay and bleaching effects that perplex development. The strategy of successive elimination of problems, a top-bottom procedure, which had been used and is usually preferred by developing agencies, might have been erroneous; a bottom-up course to delineate issues in different levels, although more laborious, might be the correct choice, especially as software and robotic hardware, high throughput tools become more mature and available. The testing for interlocus compatibility, specificity and robustness is demanding and warranted only in the case of steady, high volume use of an assay for territorial, national or international use. PMID- 27250937 TI - Prognosis following surgical bypass compared with laparotomy alone in unresectable pancreatic adenocarcinoma. AB - BACKGROUND: Resection with curative intent has been shown to prolong survival of patients with locoregional pancreatic ductal adenocarcinoma (PDAC). However, up to 33 per cent of patients are deemed unresectable at exploratory laparotomy owing to unanticipated locally advanced or metastatic disease. In these patients, prophylactic double bypass (PDB) procedures have been considered the standard of care. The aim of this study was to compare PDB with exploratory laparotomy alone in terms of impact on postoperative course, chemotherapy and overall survival. METHODS: This retrospective observational cohort study (2004-2013) was conducted using a prospective institutional database. Patients with histologically confirmed, unresectable PDAC were included. Relationships between PDB procedures, exploratory laparotomy alone, postoperative chemotherapy and best supportive care were investigated by means of Cox regression. Overall survival was compared using Kaplan-Meier estimations and log rank test. RESULTS: Of 503 patients with PDAC scheduled for resection with curative intent, 104 were deemed unresectable at laparotomy (resection rate 79.3 per cent). Seventy-four patients underwent PDB procedures and 30 had exploratory laparotomy alone. PDB and exploratory laparotomy were similar in terms of perioperative mortality, initiation of chemotherapy and overall survival. Compared with best supportive care, postoperative chemotherapy prolonged survival (8.0 versus 14.4 months in locally advanced PDAC, P = 0.007; 2.3 versus 8.0 months in metastatic PDAC, P < 0.001). Patients undergoing chemotherapy following exploratory laparotomy alone had longer median overall survival than patients undergoing chemotherapy following PDB procedures (16.3 versus 10.3 months; P = 0.040). CONCLUSION: Patients with pancreatic cancer deemed unresectable at laparotomy may derive survival benefit from subsequent chemotherapy as opposed to supportive care alone. At laparotomy, proceeding with a bypass procedure for prophylactic symptom control may be prognostically unfavourable. PMID- 27250939 TI - Using Yeast Transposon-Insertion Libraries for Phenotypic Screening and Protein Localization. AB - This protocol details how to use a transposon-insertion library for phenotypic screening and protein localization. The insertion library was generated by mutagenesis of a plasmid-based yeast genomic DNA library by using a multipurpose transposon; the transposon produces gene disruptions, and, by Cre-mediated recombination at lox sites incorporated within the transposon, alleles with an in frame insertion can be truncated to a residual transposon encoding multiple copies of the hemagglutinin epitope. Insertions are generated in yeast by shuttle mutagenesis. Yeast genomic DNA containing a transposon insertion is released from the library, and the mutagenized DNA sequences are introduced into a desired strain of yeast, where the insertion alleles replace native loci by homologous recombination. The insertion mutants can be screened for phenotypes, and the site of transposon insertion can subsequently be identified in selected mutants by inverse polymerase chain reaction (PCR). In-frame insertions within genes of interest can be truncated to an epitope-tagged allele by Cre-lox recombination, and the subcellular localization of the encoded protein product can be identified by standard methods of indirect immunofluorescence. In summary, the transposon insertion libraries represent an informative resource for large-scale mutagenesis, presenting a straightforward alternative to labor-intensive targeted approaches for the construction of deletion alleles and fluorescent protein fusions. PMID- 27250940 TI - CRISPR-Cas9 Genome Engineering in Saccharomyces cerevisiae Cells. AB - This protocol describes a method for CRISPR-Cas9-mediated genome editing that results in scarless and marker-free integrations of DNA into Saccharomyces cerevisiae genomes. DNA integration results from cotransforming (1) a single plasmid (pCAS) that coexpresses the Cas9 endonuclease and a uniquely engineered single guide RNA (sgRNA) expression cassette and (2) a linear DNA molecule that is used to repair the chromosomal DNA damage by homology-directed repair. For target specificity, the pCAS plasmid requires only a single cloning modification: replacing the 20-bp guide RNA sequence within the sgRNA cassette. This CRISPR Cas9 protocol includes methods for (1) cloning the unique target sequence into pCAS, (2) assembly of the double-stranded DNA repair oligonucleotides, and (3) cotransformation of pCAS and linear repair DNA into yeast cells. The protocol is technically facile and requires no special equipment. It can be used in any S. cerevisiae strain, including industrial polyploid isolates. Therefore, this CRISPR-Cas9-based DNA integration protocol is achievable by virtually any yeast genetics and molecular biology laboratory. PMID- 27250941 TI - Studying Lysosomal Membrane Permeabilization by Analyzing the Release of Preloaded BSA-Gold Particles into the Cytosol. AB - In addition to techniques involving assaying the release of endogenous lysosomal molecules into the cytosol, the endocytic system can be preloaded with exogenous fluorescent or electron-dense tracers. These tracers will translocate into the cytosol upon lysosomal membrane permeabilization and have the advantage of being detectable directly without additional labeling. Another benefit is that the tracers can be made more abundant than most endogenous lysosomal molecules, which facilitates their detection. Tracers that can be analyzed with fluorescence microscopy include low-molecular-mass molecules such as sulforhodamine B and also fluorescent polymers of dextran that are available in a wide range of molecular masses. This protocol shows how, for electron-microscopic analysis, cells can be fed with colloidal gold or ferrofluid particles complexed to bovine serum albumin. Although electron microscopy entails a high-resolution analysis, which can be advantageous, we caution how it is important to note that particulate tracers are larger than many endogenous lysosomal molecules and might be released only upon extensive membrane permeabilization. PMID- 27250942 TI - Chromatin and Cell Wall Staining of Schizosaccharomyces pombe. AB - Fission yeasts grow by tip extension, maintaining a constant width until they reach a critical size threshold and divide. Division by medial fission-which gives these yeast their name-generates a new end that arises from the site of cytokinesis. The old end, which was produced during the previous cell cycle, initiates progression of the new cell cycle, and in G2, the new end is activated in a process termed new-end takeoff (NETO). In this protocol, the fluorescent stains calcofluor and 4',6-diamidino-2-phenylindole (DAPI) are used to give a rapid and informative assessment of morphogenesis and cell-cycle progression in the fission yeast Schizosaccharomyces pombe Calcofluor reveals the timing of NETO because it stains the birth scars that are generated at new ends by cytokinesis less efficiently than the rest of the cell wall. Intense calcofluor staining of the septum and measurement of cell length are also widely used to identify dividing cells and to gauge the timing of mitotic commitment. Staining nuclei with DAPI identifies mono- and binucleated cells and complements the calcofluor staining procedure to evaluate the stages of the cell cycle and identify mitotic errors. Equally simple DAPI staining procedures reveal chromatin structure in higher resolution, facilitating more accurate staging of mitotic progression and characterization of mitotic errors. PMID- 27250943 TI - Staining Fission Yeast Filamentous Actin with Fluorescent Phalloidin Conjugates. AB - The Schizosaccharomyces pombe filamentous (F)-actin cytoskeleton drives cell growth, morphogenesis, endocytosis, and cytokinesis. The protocol described here reveals the distribution of F-actin in fixed cells through the use of fluorescently conjugated phalloidin. Simultaneous staining of cell wall landmarks (with calcofluor) and chromatin (with 4',6-diamidino-2-phenylindole, or DAPI) makes this rapid staining procedure highly effective for staging cell cycle progression, monitoring morphogenetic abnormalities, and assessing the impact of environmental and genetic changes on the integrity of the F-actin cytoskeleton. PMID- 27250944 TI - Cell Cycle Synchronization of Schizosaccharomyces pombe by Centrifugal Elutriation of Small Cells. AB - Division of Schizosaccharomyces pombe by medial fission produces identically sized daughter cells that grow by tip extension until their own division is prompted by reaching the same critical size for division as the parental cell. The fidelity of this size control in the absence of perturbation means that cells of the same size are at the same point in the cell cycle. Size selection of small cells from an asynchronous culture by centrifugal elutriation permits generation of synchronous cultures large enough for biochemical analysis. The changes observed in the synchronized cell cycle progression of such cultures are representative of those that accompany cell cycle progression of individual cells. Here, we describe how size selection with the Beckman Coulter JE-5.0 rotor can be used to generate synchronized cultures. Because of the continuous passage of medium through the rotor throughout the procedure, elutriation is considered to have less impact on the integrity of the cell cycle than other approaches. Two protocols are presented here: The first generates a 2-L culture ideal for detailed biochemical analysis, whereas the second allows rapid generation and simultaneous analysis of three smaller (200-mL) cultures. PMID- 27250945 TI - Cell Cycle Synchronization of Schizosaccharomyces pombe by Lactose Gradient Centrifugation to Isolate Small Cells. AB - Size selection of small cells from an asynchronous Schizosaccharomyces pombe culture offers a simple way to generate cultures in which progression through the mitotic cell division cycle is synchronized throughout the population. Here, we describe how density centrifugation of cells from asynchronous cultures through lactose gradients selects small G2 cells to generate synchronized cultures as large as 500 mL. The ease and simplicity of this approach makes it an accessible and attractive method for generating synchronous cultures. PMID- 27250946 TI - Analyzing Schizosaccharomyces pombe DNA Content by Flow Cytometry. AB - Flow cytometry can be used to measure the DNA content of individual cells. The data are usually presented as DNA histograms that can be used to examine the cells' progression through the cell cycle. Under standard growth conditions, fission yeast cells do not complete cytokinesis until after G1 phase; therefore, DNA histograms show one major peak representing cells in G1 (2*1C DNA) and G2 phase (1*2C DNA). By analysis of the duration of the fluorescence signal as well as the intensity of the DNA-related signal, it is possible to discriminate between cells in M/G1, S, and G2 This protocol describes how to prepare cells for flow cytometry and analyze them. We also describe the application of barcoding for more accurate comparison of samples. PMID- 27250947 TI - Long-Term Potentiation by Theta-Burst Stimulation Using Extracellular Field Potential Recordings in Acute Hippocampal Slices. AB - This protocol describes how to carry out theta-burst long-term potentiation (LTP) with extracellular field recordings in acute rodent hippocampal slices. This method is relatively simple and noninvasive and provides a way to sample many neurons simultaneously, making it suitable for applications requiring higher throughput than whole-cell recording. PMID- 27250948 TI - Using Multiple Whole-Cell Recordings to Study Spike-Timing-Dependent Plasticity in Acute Neocortical Slices. AB - This protocol provides a method for quadruple whole-cell recording to study synaptic plasticity of neocortical connections, with a special focus on spike timing-dependent plasticity (STDP). It also describes how to morphologically identify recorded cells from two-photon laser-scanning microscopy (2PLSM) stacks. PMID- 27250949 TI - Strategies for Assaying Lysosomal Membrane Permeabilization. AB - Late endosomal organelles have an acidic pH and contain hydrolytic enzymes to degrade cargo delivered either from the extracellular environment by endocytosis or from within the cell itself by autophagy. In the event of lysosomal membrane permeabilization (LMP), the contents of late endosomes and lysosomes can be released into the cytosol and then initiate apoptosis. Compounds that can trigger LMP are therefore candidates for the induction of apoptosis, in particular in anticancer therapy. Alternatively, drug-delivery systems, such as nanoparticles, can have side effects that can include LMP, which has toxic consequences for the cells. To determine when, to what extent, and with what consequences LMP occurs is therefore of paramount importance for the evaluation of new potentially LMP inducing compounds. In this introduction, we provide an overview of some basic assays for assessing LMP, such as staining with lysosomotropic dyes and measurement of cysteine cathepsin activity, and discuss additional strategies for the detection of the release of endogenous lysosomal molecules or preloaded exogenous tracers into the cytosol. PMID- 27250950 TI - Multipurpose Transposon-Insertion Libraries in Yeast. AB - Libraries of transposon-insertion alleles constitute powerful and versatile tools for large-scale analysis of yeast gene function. Transposon-insertion libraries are constructed most simply through mutagenesis of a plasmid-based genomic DNA library; modification of the mutagenizing transposon by incorporation of yeast selectable markers, recombination sites, and an epitope tag enables the application of insertion alleles for phenotypic screening and protein localization. In particular, yeast genomic DNA libraries have been mutagenized with modified bacterial transposons carrying the URA3 marker, lox recombination sites, and sequence encoding multiple copies of the hemagglutinin (HA) epitope. Mutagenesis with these transposons has yielded a large resource of insertion alleles affecting nearly 4000 yeast genes in total. Through well-established protocols, these insertion libraries can be introduced into the desired strain backgrounds and the resulting insertional mutants can be screened or systematically analyzed. Relative to alternative methods of UV irradiation or chemical mutagenesis, transposon-insertion alleles can be easily identified by PCR-based approaches or high-throughput sequencing. Transposon-insertion libraries also provide a cost-effective alternative to targeted deletion approaches, although, in contrast to start-codon to stop-codon deletions, insertion alleles might not represent true null-mutants. For protein-localization studies, transposon-insertion alleles can provide encoded epitope tags in-frame with internal codons; in many cases, these transposon-encoded epitope tags can provide a more accurate localization for proteins in which terminal sequences are crucial for intracellular targeting. Thus, overall, transposon-insertion libraries can be used quickly and economically and have a particular utility in screening for desired phenotypes and localization patterns in nonstandard genetic backgrounds. PMID- 27250951 TI - In Vitro Investigation of Synaptic Plasticity. AB - A classical in vitro model for investigation of information storage in the brain is based on the acute hippocampal slice. Here, repeated high-frequency stimulation of excitatory Schaeffer collaterals making synapses onto pyramidal cells in the hippocampal CA1 region leads to strengthening of evoked field recording responses-long-term potentiation (LTP)-in keeping with Hebb's postulate. This model remains tremendously influential for its reliability, specificity, and relative ease of use. More recent plasticity studies have explored various other brain regions including the neocortex, which often requires more laborious whole-cell recordings of synaptically connected pairs of neurons, to ensure that the identities of recorded cells are known. In addition, with this experimental approach, the spiking activity can be controlled with millisecond precision, which is necessary for the study of spike-timing-dependent plasticity (STDP). Here, we provide protocols for in vitro study of hippocampal CA1 LTP using field recordings, and of STDP in synaptically connected pairs of layer-5 pyramidal cells in acute slices of rodent neocortex. PMID- 27250952 TI - Intrinsic Optical Imaging of Functional Map Development in Mammalian Visual Cortex. AB - Here we describe how intrinsic imaging of the visual cortex can be used as a chronic technique. This method allows the time course of the development of cortical maps to be studied in a single animal during a period of up to 1 yr. PMID- 27250953 TI - [A Reflection on the Policy of Transcultural Long-Term Care for the Indigenous Peoples in Taiwan]. AB - Giving high-profile attention to socio-cultural and traditional beliefs in the promotion of long-term care policies enjoys strong, consensus support in the field of transcultural nursing. To protect the rights of indigenous people in Taiwan, the Ministry of Health and Welfare incorporated the concept of cultural care into the Long-term Care Services Act, which was approved by the Legislature in May 2014. However, the policies, resource strategies, manpower allocations, and staff educations and trainings related to this act are still await implementation in indigenous areas. Beyond the concept of professional healthcare, which considers cultural sensitivity, suitability, and ability, cultural care gives greater priority to crossing cultural barriers, integrating with the lifestyle of clients, and addressing their concerns in order to improve the well-being of target populations. The present article reviews current long term care policy to highlight the importance of considering the cultural needs of the indigenous peoples of Taiwan in order to enhance the efficiency and impact of long-term care programs. Furthermore, the findings strongly recommend that additional resources be provided in order to meet the long-term care needs of indigenous communities. Finally, cultural-specific, long-term care service strategies should be promulgated in order to upgrade well-being in order to ease and comfort the feelings of indigenous people. PMID- 27250954 TI - [Reflection on the Health and Gender Mainstreaming of Indigenous Women in Taiwan]. AB - Gender and race issues have caused rapid cultural and societal changes to affect the healthcare of indigenous women, which involves complicated, cultural meanings. The present paper begins by outlining the gender perspective and then elaborates on the present gender mainstreaming and status of indigenous women's healthcare in Taiwan. Furthermore, this paper identifies the current difficulties experienced by Taiwanese indigenous women, including those related to the lack of adequate healthcare data and gender analyses on indigenous women and the lack of regular research on healthcare strategies for indigenous women. Therefore, the present paper proposes to establish health policy references that are gender and race sensitive. The health policy not only addresses racial and gender concerns regarding healthcare information but also focuses on the analysis of indigenous healthcare information. Indigenous women's health concerns are discussed here within the framework of healthcare policy through the perspective of gender mainstreaming. Additionally, we will analyze and evaluate the effects of gender in order to establish inspection and management processes that integrate the concept of gender into policy development and implementation, thus promoting relevant health policies. During the processes of planning, implementing, and evaluating healthcare policies, women should unite to contribute toward indigenous women's health policies and gender mainstreaming. PMID- 27250955 TI - [How are You, My Tribe? The Health Relationship Among the Tribe, Ethnic Group, and the Self]. AB - Most papers on the status of indigenous health focus on health problems from the individual perspective in the hope that this will spread from the individual to tribal/ethnic perspectives. For most indigenous people, the 'tribe' is their home and this home has been affected by colonial society, which has changed tribal ethics and influenced the status of indigenous health. Similarly, there are fissures in the links between indigenous people and their tribes, their ancestry, and their land because of the loss of their land, traditional culture, and racial discrimination and prejudice. These result in an imbalance between indigenous people and their environment and have a deeply felt influence on indigenous health. Transitional justice is an approach to coping with these issues that include colonization, capitalism, relationships with production, and promoting indigenous health. PMID- 27250956 TI - [The Development of Research Ethics Involving Indigenous People in Taiwan: A Brief Introduction]. AB - Adhering to ethics protocols has become increasingly important in the process of doing research in Taiwan since the introduction of research-ethics mechanisms. Adhering to these protocols affects research on Taiwan's indigenous peoples due to the vulnerability of indigenous groups and to their increasing rights consciousness. The present paper explains the context of group rights from a national self-determination perspective and then discusses the current indigenous research-ethics mechanisms in Taiwan. The ethical guidelines for indigenous research in Canada, TCPS2 2014-Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans are referenced as a model for protocols that may foster positive and mutually trusting relationships between academic researchers and indigenous communities in Taiwan. PMID- 27250957 TI - [Exploring the Care Needs of Primary Caregivers of Patients Awaiting Brain Tumor Surgery and Related Factors]. AB - BACKGROUND: The prognosis of patients with brain tumor diagnoses is often uncertain. Therefore, the primary caregivers of these patients must not only adjust their lives to patient care but also often deal with patient anxiety and depression, which may significantly increase patient-care needs. PURPOSE: The present study explores the care needs of primary caregivers of patients awaiting brain tumor surgery and the factors that are associated with these needs. METHODS: A correlational research design was used. Convenience sampling was used to recruit 80 pre-brain-tumor operation patient/caregiver pairs. Data were collected using a questionnaire survey, which included Supportive Care Needs Survey-Partners & Caregivers 45 (SCNS-P&C45) and the Hospital Anxiety and Depression Scales (HADS). Descriptive and inferential statistics were used for data analysis. RESULTS: The information-needs and healthcare-service-needs subscales earned the highest subscale scores on the SCNS-P&C45. Higher anxiety perception (r = .37, p < .01) and higher depression status (r = .27, p < .05) were significantly correlated with increased care needs. In addition, decreased patient functional status was significantly associated with increased depression in the primary caregiver. Anxiety perception was the only significant predictor of care needs that was identified (R(2) = 12.8%). CONCLUSIONS: Healthcare providers should provide patient education on the disease and disease-related care information soon after a diagnosis of brain tumor in order to decrease the anxiety and depression perceptions of caregivers and to reduce the care needs of caregivers. PMID- 27250958 TI - [Reliability and Validity Testing of the Taiwanese Inpatient Nursing Care Satisfaction Scale: A Pilot-Study]. AB - BACKGROUND: Inpatient nursing care satisfaction is an important indicator of medical care quality. However, no reliable and validated tool is currently available in Taiwan to measure the satisfaction of inpatients with nursing care. PURPOSE: This pilot study developed a reliable and validated scale for measuring inpatient nursing care satisfaction in Taiwan. METHODS: First phase: literature review and expert focus group discussion constructs the content of the questionnaire to be used to assess inpatient nursing care satisfaction. Second phase: experts were requested to validate questionnaire content. Third phase: convenience sampling was used to recruit 766 inpatients from 6 hospitals to complete the validated questionnaire. The data collected from the questionnaire were analyzed using item analysis, construct validity, and internal consistency. The results of analysis were used to determine the reliability and validity of the developed scale. RESULTS: The 20-item Taiwanese inpatient nursing care satisfaction scale was developed, with a CVI (content validity index) of expert validity of .97, item discrimination CR (critical ratio) of 28.61-50.25 (p < .001), and item-total correlation of .68-.84 (p < .001). Two factors, including "professional knowledge & skill" and "environmental control" were extracted by exploratory factor analysis after the deletion of 5 items, with item factor loadings ranging from .61 to .84. The factors explained 71.40% of total variance. The internal consistency of the two categories of Cronbach's alpha was .94-.97 coefficient and the overall internal consistency coefficient was .97. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This study confirms the validity of the developed Taiwanese inpatient nursing care satisfaction scale and suggests that this instrument is reliable for measuring the satisfaction of inpatients with nursing care in Taiwan. PMID- 27250959 TI - [The Childbearing Experiences of Taiwanese Women After a Stillbirth]. AB - BACKGROUND: Perinatal losses are traumatic events for women and may have serious long-term consequences for the psychological health of women and subsequent pregnancies. Therefore, it is important to explore the psychological adaptation process of subsequent pregnancy after loss in order to understand the overall phenomenon of perinatal loss. PURPOSE: To explore the childbearing experiences of women who have experienced a prior stillbirth. METHODS: This qualitative descriptive study targeted a purposive sample of 15 women who had prior personal experiences with stillbirth. A total of 22 in-depth interviews were conducted in order to ensure data saturation. Women who had experienced stillbirth at one of two teaching hospitals in southern Taiwan were recruited. Data were analyzed using content analysis. RESULTS: Three themes were identified that captured the complex feelings of participants regarding their subsequent childbearing experiences: (1) looking forward to another pregnancy but afraid of being hurt again, (2) treading on thin ice, and (3) bearing another child helps heal the loss of the stillborn. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The empirical data gathered in the present study helps build a more complete understanding of the process of recovery that women undergo following a stillbirth experience. In addition, the results suggest that healthcare professionals should be aware of and accept the worries and reactions of women during their subsequent pregnancy in order to help these women achieve a positive subsequent childbearing experience. PMID- 27250960 TI - [Exploration of the Care Needs of Post-Chemotherapy Lung Cancer Patients and Related Factors]. AB - BACKGROUND: Chemotherapy (CT) is the first priority treatment for advanced stage lung cancer. However, symptom distress, impaired ability to conduct daily activities, and post-CT care needs are potential side effects of CT. PURPOSE: To explore the factors related to the care needs of post-chemotherapy lung cancer patients. METHODS: A cross-sectional study was used. One hundred and twenty-one adult patients who had been diagnosed with advanced-stage lung cancer and who had undergone CT using the Platinum and Docetaxel doublet regimen were recruited from a medical center in southern Taiwan. The instruments used included a nursing care needs survey, symptoms distress scale, daily activity interference scale, and patient characteristics datasheet. RESULTS: Participants self-prioritized their emergency management, health consultation, and emotional support activities based on their perceived care needs. The top three post-CT symptoms in terms of severity were: fatigue, appetite change, and sleep disorder. Primary disruptions in daily activities during the post-CT period related to: holding social activities, work, and stair climbing. Significant and positive correlations were found among daily activity interference (r = .30, p < .01), symptoms distress (r = .23, p < .01), and care needs. The regression model indicated daily activity interference as a predictor of care needs, accounting for 10.7% of the total variance. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: These results highlight the relationships among care needs, symptom distress, and daily activity interference in post-chemotherapy lung-cancer patients. The present study provides a reference for nursing care to reduce the symptom distress, to enhance the performance of daily activities, and to meet the care needs of lung-cancer patients. PMID- 27250961 TI - [The Effectiveness of Different Corticosteroid Injections in Patients With Carpal Tunnel Syndrome: A Bayesian Network Meta-Analysis]. AB - BACKGROUND: Corticosteroid injection is one of the interventions used to alleviate the symptoms of carpal tunnel syndrome. The consistency across domestic and overseas studies of the results of corticosteroid injections in terms of easing carpal tunnel syndrome has not previously been analyzed. PURPOSE: This meta-analysis explored the symptom severity and functional status of different corticosteroid injection strategies in treating patients with carpal tunnel syndrome. METHODS: A systematic review was performed, keywords including: carpal tunnel syndrome, corticosteroid [Title/Abstract], placebo, disability, and pain intensity were used to query electronic databases, including Cochrane Library, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ProQuest, PubMed database. All of the articles that were indexed on these databases, met the inclusion criteria, and were published prior to June 2015 were extracted for analysis. A standardized critical appraisal tool from the "Cochrane Handbook Systematic Reviews of Intervention" to assess the risk of bias tool was used to assess methodological quality. WinBUGS software was used to conduct the meta analysis. RESULTS: The 10 articles that were qualified and used in the present study contained a total of 633 participants. Median symptom severity was -1.16 (95%CrI [-1.95, .38]) on the symptom severity scale for ultrasound-guided in plane injection among patients with carpal tunnel syndrome. The surface under the cumulative ranking curve (SUCRA) achieved 95%. The median MD was -.74 (95%CrI [ 2.0, .52]) on the functional status scale for ultrasound-guided in-plane injection among patients with carpal tunnel syndrome. The (SUCRA) achieved 78%. The results indicate that the three injection methods reduced the severity and improved the functional status in comparison with the placebo, ultrasound-guided in-plane corticosteroid injection. CONCLUSIONS: Corticosteroid injections alleviate symptom severity and promote functional status in patients with carpal tunnel syndrome. Ultrasound-guided in-plane injections demonstrated greater effectiveness. The network meta-analysis provides a reference for rehabilitation nursing. PMID- 27250962 TI - [A Systematic Review of the Literature Related to Elevating the Head of the Bed for Patients With Gastroesophageal Reflux Disease: Applications in Patients After Esophageal Cancer Surgery]. AB - BACKGROUND: Acid regurgitation typically worsens during nighttime sleep, which influences the quality of life of patients and potentially causes pathological changes. As much as 80% of esophageal cancer patients experience acid regurgitation following esophagectomy and reconstruction surgery. Thus, improving this symptom is important to improving the quality of life of these patients. PURPOSE: The purpose of the present study was to evaluate the effect of elevating the head of the bed for patients with gastroesophageal reflux disease (GERD). METHODS: A systematic review was used. Electronic databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Library, ProQuest, and PubMed/MEDLINE were retrieved for relevant articles that were published prior to June 2015. Keywords included "elevating the head of the bed/bed position/body position", "flat", "reflux", and the MeSh term "gastroesophageal reflux". A total of 37 articles that matched the search criteria were extracted. After screening the topics and deleting repetitions, three randomized controlled studies and one quasi-experimental designed study were selected. RESULTS: Results of this systemic review revealed that elevating the head of the bed for patients with GERD reduced the duration of exposure of the the esophagus to an acid environment. Furthermore, patients perceived that this intervention not only improved symptoms such as regurgitation and burn sensation without medication but also relieved symptoms better than taking medications alone. CONCLUSIONS: The reviewed studies support that elevating the head of the bed is an easy and effective way to alleviate the symptoms of acid regurgitation. A height of elevation of 20 to 28 cm is recommended in the literature. The slope of the elevated bed must also be considered. Elevating the head of the bed may be useful for improving acid regurgitation among esophageal cancer patients after surgery. A randomized controlled study may be used to validate this effect in the future. PMID- 27250963 TI - [The Effectiveness of Pulmonary Rehabilitation for Critical-Care Ventilator Patients: A Systematic Review]. AB - BACKGROUND: Prolonged of use mechanical ventilators results in respiratory muscle atrophy and difficulties in weaning, which increase mortality rates and psychlogical distress. While pulmonary rehabilitation has been shown to improve respiratory muscle strength, the effects of this intervention in critical-care patients who use mechanical ventilation remain uncertain. PURPOSE: The present paper uses a systematic review of the literature to evaluate the effects of pulmonary rehabilitation on the rate of ventilator weaning and on the physical performance of ventilator patients receiving critical care. METHODS: A systematic review was used. Searches were conducted in databases including: Cochrane Library, Embase, MEDLINE, PubMed and Airit Library. Keywords that were used included: "mechanical ventilation", "pulmonary rehabilitation", "exercise", "weaning", and "activities of daily living". The search focused on articles that were published prior to February 2015. Based on inclusion and exclusion criteria, 7 articles addressing relevant randomized controlled trials were extracted. RESULTS: All of the 7 studies supported that pulmonary rehabilitation interventions improve mechanical ventilation weaning and functional independence activities. Several studies were limited by small sample size and differences in the types of rehabilitations used. Thus, the generalizability of the findings of this review is limited. and further research is required to verify the effects of pulmonary rehabilitation. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results of this systematic review support that pulmonary rehabilitation interventions improved the weaning rate, activities of functional independence, and maximal inspiratory pressure (MIP) in critical patients who had used mechanical ventilators for over 48 hours. Under hemodynamic-stablized and pressure-support mode, inspiratory muscle training is suggested as useful for patients with limited ability to participate in rehabilitation programs. PMID- 27250964 TI - [Constructing an ACP Simulation-Situation Communication Training Program for Patients With Chronic Kidney Disease]. AB - The aging population and changing lifestyles have lead to the increased general risk of chronic kidney disease. Taiwan currently has the highest incidence and prevalence of end-stage renal disease (ESRD) of any country or region in the world. Hemodialysis patients must endure comorbidities and face the uncertainties of death. The best way to achieve a good death is for patients to sign advance care planning (ACP). However, the key factors contributing to low ACP signature rates have been the lack of communication skills and related training among medical staffs. This article explores the dilemma of ACP using an example of chronic kidney disease (CKD) and proposes a theory-based approach to develop a theoretical framework for an ACP simulation-situation communication training program that integrates the simulation situation model, PREPARED model, and scaffolding theory. Readers may use this framework to design ACP simulation situation communication training programs that conform to their own conditions and then test the effectiveness and feasibility of these programs in clinical settings. PMID- 27250965 TI - [Improving the Care Accuracy of Percutaneously Inserted Central Catheters Using Objective Structured Clinical Examination]. AB - Approximately 9,800 adverse events related to medical tubing are reported in Taiwan every year. Most neonates in critical condition and premature infants acquire fluid, nutrition, and infusion solution using percutaneously inserted central catheters (PICCs). Objective structured clinical examination (OSCE) is an objective evaluative tool that may be used to measure the clinical competence of healthcare professionals. Very little is known about the effects of OSCE in Taiwan in terms of improving the accuracy of use of PICCs in nursing care and of reducing unexpected medical tubing removals. The present project aimed to explore the effects of an OSCE course on these two issues in the realms of standard operating procedures, care protocols, and training equipment at a neonatal intermediate unit in Taiwan. The duration of the present study ran from 2/20/2013 to 10/30/2013. The results showed that nurses' knowledge of PICCs improved from 87% to 91.5%; nurses' skill-care accuracy related to PICCs improved from 59.1% to 97.3%; and incidents of unexpected tube removals declined from 63.6% to 16.7%. This project demonstrated that OSCE courses improve the quality of PICC nursing care. Additionally, the instant feedback mechanism within the OSCE course benefited both teachers and students. PMID- 27250966 TI - [The Efficacy of Rooming-In in the Context the Physical and Mental Health of New Mothers]. AB - The Breastfeeding-Friendly Policy promotes successful breastfeeding by encouraging postpartum rooming-in and other practices that have been shown to increase breastfeeding success. Puerperium is a key transition period in a woman's life during which she faces physical changes as well as changes in roles and tasks as she transitions into motherhood. During this transition period, postpartum women typically follow the rooming-in and breastfeeding practices that are recommended by the hospital. However, without suitable assistance, the physical and mental problems that often accompany childbirth may impact the postpartum health of the mother. This article reflects on the potential health problems that are encountered by postpartum women who adopt 24-hour rooming-in practices from the perspective of their health rights and proposes suggestions for improving these practices as a reference for related government and healthcare workers. PMID- 27250967 TI - The positive association between elevated blood lead levels and brain-specific autoantibodies in autistic children from low lead-polluted areas. AB - The underlying pathogenic mechanism in autoimmune disorders is the formation of autoantibodies. In children with autism spectrum disorder (ASD), it has been documented increased levels of brain-specific autoantibodies. Furthermore, lead (Pb) has been identified as one of the main neurotoxicants acting as environmental triggers for ASD as it induces neuroinflammation and autoimmunity. The present study is the first to explore a potential relationship between the levels of blood lead (BPb) and seropositivity of anti-ribosomal P protein antibodies in ASD children. Levels of BPb and serum anti-ribosomal P protein antibodies were measured in 60 children with ASD and 60 healthy control matched children, aged between 5 and 12 years, recruited from low Pb-polluted areas. The levels of BPb were significantly higher in ASD children than in healthy control children (P < 0.001). Patients with ASD had significantly higher frequency of increased BPb levels >=10 MUg/dL (43.3 %) than healthy control children (13.3 %; P < 0.001). There were significant and positive correlations between the levels of BPb, and the values of Childhood Autism Rating Scale (CARS) (P < 0.01) and IQ in children with ASD (P < 0.001). Patients with ASD showing increased levels of BPb had significantly higher frequency of seropositivity of anti-ribosomal P antibodies (92.3 %) than patients with normal BPb levels (32.3 %; P < 0.001). The findings of the present study suggest that increased levels of BPb in some children with ASD may trigger the production of serum anti-ribosomal P antibodies. Further research is warranted to determine if the production of brain autoantibodies is triggered by environmental Pb exposure in children with ASD. The possible therapeutic role of Pb chelators in ASD children should also be studied. PMID- 27250968 TI - Methylglyoxal-induced neuroinflammatory response in in vitro astrocytic cultures and hippocampus of experimental animals. AB - Diabetes mellitus is characterized by chronic hyperglycemia and its diverse complications. Hyperglycemia is associated with inflammatory responses in different organs and diabetic patients have a higher risk of developing neurodegenerative disorders. Methylglyoxal is a reactive advanced glycation end product precursor that accumulates in diabetic patients. It induces various stress responses in the central nervous system and causes neuronal dysfunction. Astrocytes are actively involved in maintaining neuronal homeostasis and possibly play a role in protecting the brain against neurodegeneration. However it is not clear whether methylglyoxal exerts any adverse effects towards these astrocytes. In the present study we investigated the effects of methylglyoxal in astrocytic cultures and hippocampi of experimental animals. The cells from the astrocytic line DITNC1 were treated with methylglyoxal for 1 to 24 h. For the in vivo model, 3 months old C57BL/6 mice were treated with methylglyoxal solution for 6 weeks by intraperitoneal injection. Following the treatment, both astrocytes and hippocampi were harvested for MTT assay, Western blot and real time PCR analyses. We found that methylglyoxal induced astrogliosis in DITNC1 astrocytic cultures and C57BL/6 mice. Further, activation of the pro-inflammatory JNK signaling pathway and its downstream effectors c-Jun were observed. Furthermore, increased gene expression of pro-inflammatory cytokines and astrocytic markers were observed from real time PCR analyses. In addition, inhibition of JNK activities resulted in down-regulation of TNF-alpha gene expression in methylglyoxal treated astrocytes. Our results suggest that methylglyoxal may contribute to the progression of diabetes related neurodegeneration through JNK pathway activation in astrocytes and the subsequent neuroinflammatory responses in the central nervous system. PMID- 27250969 TI - Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer. AB - Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival. Since 2013 nab-paclitaxel (paclitaxel-albumin-bound particles) became a new treatment option for patients with metastatic pancreatic cancer based on the results of MPACT trial. Moreover, encouraging activity in PDAC of the combination regimen of paclitaxel and carboplatin that is being widely used in other solid tumors has been reported recently. Biomarkers, including biomarkers predictive of taxane resistance, could allow individualized tailored therapy. BRCA mutation status could serve as predictor of better chemotherapy treatment outcome in PDAC. The present review summarizes the principal clinical trials evaluating the efficacy of taxanes both as monotherapy and in combination in view of the potential use in the treatment of PDAC. PMID- 27250971 TI - Teriparatide and denosumab combination therapy and skeletal metabolism. AB - : Several therapies are available for osteoporis. Understanding the bone turnover changes and their mutual realtionship gives an overall view and might lead to a target therapy INTRODUCTION: The aim of this study is to compare the changes in bone turnover markers in patients treated with either denosumab alone, teriparatide (TPTD) alone, or in a third therapeutic scheme, when TPTD was added to patients previously treated with denosumab. METHODS: Fifty-nine women over 65 years old with severe postmenopausal osteoporosis (evidence of at least two moderate-severe vertebral fractures) were enrolled in the study. Serum samples were collected every 3 months. They were assayed for intact N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), intact parathyroid hormone (PTH), 25 hydroxy-vitamin D (25 OHD), Sclerostin (SOST), and Dickkopf-related protein 1 (DKK1). Bone mass density was assessed by dual-energy X-ray absorptiometry at the lumbar spine and at the total hip. RESULTS: In the groups treated only with TPTD or with denosumab, bone turnover markers increased and decreased, respectively. In TPTD group, a later significant increase in DKK1 was observed, while in denosumab group, a progressive increase in SOST was associated with a progressive significant decrease in DKK1. In the group treated first with denosumab and in which TPTD was added 3 months later, both CTX and P1NP increased 3 months after the beginning of TPTD. The strong effect of denosumab on bone turnover seems to be reversed by TPTD treatment. CONCLUSIONS: In this study, we showed that TPTD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST. PMID- 27250970 TI - Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response. AB - Pulmonary surfactant is a complex fluid that comprises phospholipids and four proteins (SP-A, SP-B, SP-C, and SP-D) with different biological functions. SP-B, SP-C, and SP-D are essential for the lungs' surface tension function and for the organization, stability and metabolism of lung parenchyma. SP-A and SP-D, which are also known as pulmonary collectins, have an important function in the host's lung immune response; they act as opsonins for different pathogens via a C terminal carbohydrate recognition domain and enhance the attachment to phagocytic cells or show their own microbicidal activity by increasing the cellular membrane permeability. Interactions between the pulmonary collectins and bacteria or viruses have been extensively studied, but this is not the same for fungal pathogens. SP-A and SP-D bind glucan and mannose residues from fungal cell wall, but there is still a lack of information on their binding to other fungal carbohydrate residues. In addition, both their relation with immune cells for the clearance of these pathogens and the role of surfactant proteins' regulation during respiratory fungal infections remain unknown. Here we highlight the relevant findings associated with SP-A and SP-D in those respiratory mycoses where the fungal infective propagules reach the lungs by the airways. PMID- 27250973 TI - Next-generation sequencing for virus detection: covering all the bases. AB - BACKGROUND: The use of next-generation sequencing has become an established method for virus detection. Efficient study design for accurate detection relies on the optimal amount of data representing a significant portion of a virus genome. FINDINGS: In this study, genome coverage at different sequencing depths was determined for a number of viruses, viroids, hosts and sequencing library types, using both read-mapping and de novo assembly-based approaches. The results highlighted the strength of ribo-depleted RNA and sRNA in obtaining saturated genome coverage with the least amount of data, while even though the poly(A) selected RNA yielded virus-derived reads, it was insufficient to cover the complete genome of a non-polyadenylated virus. The ribo-depleted RNA data also outperformed the sRNA data in terms of the percentage of coverage that could be obtained particularly with the de novo assembled contigs. CONCLUSION: Our results suggest the use of ribo-depleted RNA in a de novo assembly-based approach for the detection of single-stranded RNA viruses. Furthermore, we suggest that sequencing one million reads will provide sufficient genome coverage specifically for closterovirus detection. PMID- 27250972 TI - Systemic markers of microvascular disease and bone mineral density in older adults : The cardiovascular health study. AB - : Here we report that abnormal brain white matter and, to a lesser extent, albuminuria are associated with reduced bone mineral density in the hip, spine, and total body in men and women. These findings may explain the increased hip fracture risk reported in some studies in association with microvascular disorders. INTRODUCTION: Markers of microvascular disease have been individually associated with increased risk of osteoporotic fractures in some studies. Here, we examine whether these markers are associated with reduced bone mineral density (BMD) individually and together. METHODS: BMD testing using dual x-ray absorptiometry of the hip, lumbar spine, and total body was performed in 1473 participants from the Cardiovascular Health Study (mean age ~ 78 years): 1215 were assessed for urinary albumin-creatinine ratio, 944 for abnormal white matter disease (AWMD) by brain MRI, and 541 for retinal vascular disease with fundus photographs. Linear regression models were used to evaluate the cross-sectional association of each marker with BMD accounting for potentially confounding factors. RESULTS: AWMD was associated with lower hip, spine, and total body BMD in women (beta -3.08 to -4.53; p < 0.01 for all) and lower hip and total body BMD in men (beta -2.90 to -4.24; p = 0.01-0.03). Albuminuria was associated with lower hip (beta -3.37; p = .05) and total body (beta -3.21; p = .02) BMD in men, but not in women. The associations of AWMD and albuminuria with BMD persisted with mutual adjustment and appeared to be additive to each other. Retinal vascular disease was not associated with BMD in men or women. CONCLUSION: AWMD and, to a lesser extent, albuminuria were independently associated with lower BMD, suggesting that microvascular disease may play a role in the pathogenesis of reduced BMD. These findings need to be confirmed by longitudinal studies. PMID- 27250974 TI - Aneurysmal dilatation of torcular herophili. PMID- 27250975 TI - The floating cardiac fat pad-sign of occult pneumothorax. AB - Pneumothoraces are a possible sequela of chest trauma with potential morbidity and mortality if not recognized and treated promptly. A portable supine chest radiograph is frequently the first radiologic study performed in the setting of trauma. While large pneumothoraces can be readily recognized on these radiographs, smaller pneumothoraces are missed in up to 15 % of trauma patients. There are many radiographic signs of occult pneumothoraces, and we are presenting a new radiographic sign of occult pneumothorax. The floating cardiac fat pad sign occurs when pleural air collects anteriorly and superiorly in the most non dependent portion of the chest lifting the pericardial fat pad off the diaphragm. Lung markings are still seen surrounding the pericardial fat pad due to the inflated lower lobe of the lung resting dependently. Rapid and accurate identification of pneumothoraces is critical but often difficult on chest radiographs. Although there are many existing radiographic signs for identification of pneumothorax, prospective identification of small pneumothoraces is still relatively poor. Here, we describe an additional sign which aides in the detection of pneumothoraces, the floating cardiac fat pad. When present, this should prompt further evaluation with chest CT or upright chest radiograph. PMID- 27250976 TI - Diagnostic performance of CT angiography in neck vessel trauma: systematic review and meta-analysis. AB - This study was conducted in order to define the diagnostic performance of CT angiography for vascular injuries compared with angiography in patients with neck trauma. CT angiography is the cornerstone of diagnosis for hemodynamically stable patients with wounds suspicious of vascular trauma in the limbs, chest, or abdomen. Available evidence for the use of CT angiography in neck vascular trauma comes from small case series and few randomized controlled trials, and high quality information does not exist regarding its performance. A protocol using the recommendations of the Cochrane Collaboration was designed. A systematic search of diagnostic studies without limits on language or time was carried out to December 2014. Studies including patients with neck trauma with retrospective or prospective data collection that assessed CT angiography compared with other methods were selected. Methodological quality was assessed using the QUADAS-2 tool. A hierarchical model ROC curve and a bivariate random effects model were used for the pooled analysis. Sixteen studies were selected and reviewed, and nine studies with 693 patients were included in this review. The overall sensitivity was 97 % (95 % CI 0.77-1.00; I (2) = 65.7 % (41.4-90.0)), while the overall specificity was 99 % (95 % CI 0.93-1.00; I (2) = 0). The hierarchic ROC curve showed an area under the curve of 0.99. Publication bias was not identified in this study. CT angiography can be stated as the gold standard for diagnosing vascular injuries in hemodynamically stable patients with neck trauma. PMID- 27250979 TI - Breast self examination error. PMID- 27250977 TI - Resting-State Functional Connectivity Changes Between Dentate Nucleus and Cortical Social Brain Regions in Autism Spectrum Disorders. AB - Autism spectrum disorders (ASDs) are known to be characterized by restricted and repetitive behaviors and interests and by impairments in social communication and interactions mainly including "theory of mind" (ToM) processes. The cerebellum has emerged as one of the brain regions affected by ASDs. As the cerebellum is known to influence cerebral cortex activity via cerebello-thalamo-cortical (CTC) circuits, it has been proposed that cerebello-cortical "disconnection" could in part underlie autistic symptoms. We used resting-state (RS) functional magnetic resonance imaging (fMRI) to investigate the potential RS connectivity changes between the cerebellar dentate nucleus (DN) and the CTC circuit targets, that may contribute to ASD pathophysiology. When comparing ASD patients to controls, we found decreased connectivity between the left DN and cerebral regions known to be components of the ToM network and the default mode network, implicated in specific aspects of mentalizing, social cognition processing, and higher order emotional processes. Further, a pattern of overconnectivity was also detected between the left DN and the supramodal cerebellar lobules associated with the default mode network. The presented RS-fMRI data provide evidence that functional connectivity (FC) between the dentate nucleus and the cerebral cortex is altered in ASD patients. This suggests that the dysfunction reported within the cerebral cortical network, typically related to social features of ASDs, may be at least partially related to an impaired interaction between cerebellum and key cortical social brain regions. PMID- 27250978 TI - General and social cognition in remitted first-episode schizophrenia patients: a comparative study. AB - The aim of this paper was to investigate whether both neurocognitive and social cognitive performances were different between remitted first-episode schizophrenia patients, non-remitters and healthy controls (HC). We assessed social cognition (Degraded Facial Affect Recognition Task-DFAR and Emotional Mentalizing Task-EMT) and neurocognition (Wechsler Adult Intelligence Scale and Word Learning Test-WLT) in 174 remitted first-episode schizophrenia patients, 110 non-remitted first-episode schizophrenia patients and 320 HC. Multivariate analyses of variance with age, gender and IQ as covariates (MANCOVA) were performed to compare mean cognitive test scores between the three groups. Remitted first-episode schizophrenia patients performed significantly worse than HC only in one verbal memory task (WLT immediate recall; p = 0.004); in the same test, they were significantly better than non-remitters (p = 0.027). Non-remitted first-episode schizophrenia patients, differently from remitters, performed significantly worse than HC in terms of social cognition (EMT-p < 0.05 and DFAR-p < 0.05). Remitted first-episode schizophrenia patients presented worse cognitive performance than HC in verbal memory tasks, but not in facial affect recognition and in ToM, while non-remitters did; these results suggest that neurocognitive deficits are the core hallmark of schizophrenia and that social cognition is relatively unaffected in remitted patients after their first episode. PMID- 27250980 TI - The 2010-2015 Prevalence of Eosinophilic Esophagitis in the USA: A Population Based Study. AB - BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder with increasing prevalence. However, epidemiologic data have mostly been acquired from small studies. We sought to describe the epidemiology of EoE in the USA, utilizing a large database. METHODS: We queried a commercial database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems from 1999 to July 2015. We identified an aggregated patient cohort of eligible patients with EoE and a history of proton-pump inhibitor use between July 2010 and July 2015, based on Systematized Nomenclature of Medicine-Clinical Terms. We calculated the prevalence of EoE among different patient groups. RESULTS: Of the 30,301,440 individuals in the database, we identified 7840 patients with EoE with an overall prevalence of 25.9/100,000 persons. Prevalence was higher in males than females [odds ratio (OR) 2.00; 95 % CI 1.92-2.10, p < 0.0001], Caucasians versus African Americans and Asians (OR 2.00; 95 % CI 1.86-2.14, p < 0.0001), and adults (18-65 years) versus elderly (>65 years) and children (<18 years) (OR 1.63; 95 % CI 1.54 1.71, p < 0.0001). Compared with controls (individuals in database without EoE), individuals with EoE were more likely to have other gastrointestinal diagnoses such as dysphagia and at least one allergic condition. CONCLUSIONS: In this large study, we found that the estimated prevalence of EoE in the USA is 25.9/100,000, which is at the lower end of prevalence rates reported in the USA and other industrial countries. We confirmed that EoE has a strong association with allergic and gastrointestinal diagnoses. PMID- 27250982 TI - Early Detection of Steatohepatitis: Less Teeth NASHing and More Research? PMID- 27250981 TI - Is Gastric Xanthelasma an Alarming Endoscopic Marker for Advanced Atrophic Gastritis and Intestinal Metaplasia? AB - BACKGROUND/AIM: The clinical significance of gastric xanthelasmas is unknown. We conducted a case-control study in order to evaluate whether gastric xanthelasma is an indicator of advanced atrophic gastritis and intestinal metaplasia. MATERIAL AND METHOD: The study was conducted among 1400 patients who underwent elective upper endoscopy. Patients with gastric xanthelasma and atrophy and/or intestinal metaplasia constituted the study group (n = 55). The control group involved patients with only atrophic gastritis and/or intestinal metaplasia (n = 50). Histopathologic findings of the groups including the distribution of atrophic gastritis and/or intestinal metaplasia, operative link on gastritis assessment score, operative link on gastritis intestinal metaplasia assessment (OLGIM) score, and presence of dysplasia and malignancy were compared. Subgroup analysis was performed in order to establish the relation between the characteristics (size, number, and localization) of xanthelasmas, atrophy, and intestinal metaplasia. RESULTS: Multifocal atrophic gastritis was significantly more common in patients with a gastric xanthelasma (41.8 vs. 26.0 %, p = 0.03). Patients with multiple xanthelasmas had a significantly higher rate of intestinal metaplasia (p = 0.02) and a higher OLGIM score (p = 0.02) compared to those with a single xanthelasma. Dysplasia was detected in 8 (14.5 %) patients with a xanthelasma and 4 (8.0 %) patients without a xanthelasma (p = 0.2). CONCLUSION: Gastric xanthelasma(s) is a warning endoscopic sign for the presence of multifocal atrophic gastritis and advanced intestinal metaplasia. PMID- 27250983 TI - P2Y1, P2Y2, and TRPV1 Receptors Are Increased in Diarrhea-Predominant Irritable Bowel Syndrome and P2Y2 Correlates with Abdominal Pain. AB - BACKGROUND: Previous studies indicated that P2Y1 and P2Y2 receptors, which are widely distributed in the enteric nervous system, are related to pain, while TRPV1 may contribute to visceral pain and hypersensitivity states in irritable bowel syndrome (IBS). Other studies showed that ATP activates the capsaicin sensitive TRPV1 channel via P2Y receptors. AIM: To detect the expression of P2Y1, P2Y2, and TRPV1 receptors in diarrhea-predominant IBS (IBS-D) patients and analyze any correlations with abdominal pain and to investigate interactions between P2Y receptors and the TRPV1 receptor in IBS-D patients. METHODS: Rectosigmoid biopsies were collected from patients with IBS-D (n = 36) and healthy controls (n = 15). Abdominal pain was scored using a 10-cm visual analogue scale. Expression levels of P2Y1, P2Y2, and TRPV1 receptors in rectosigmoid biopsies were determined by real-time PCR and double-labeling immunofluorescence with specific antibodies. RESULTS: Both mRNA and protein expression levels of P2Y1, P2Y2, and TRPV1 receptors were increased in IBS-D compared with controls. Of these receptors, P2Y2 expression correlated with the maximum pain scores (p = 0.02, r = 0.63, Spearman correlation) in IBS-D patients. However, no relationships were detected between P2Y receptors and the TRPV1 receptor. CONCLUSION: In the present study, we identified an increased expression of P2Y1 and P2Y2 receptors in the rectosigmoid mucosa of IBS-D patients, and P2Y2 correlated with abdominal pain. Furthermore, we identified an increase in TRPV1 expression; however, there were no correlations found between P2Y receptors and the TRPV1 receptor. PMID- 27250985 TI - Prediction of Postoperative Complications Following Elective Surgery in Elderly Patients with Colorectal Cancer Using the Comprehensive Geriatric Assessment. AB - AIMS: The study aims to determine whether the Comprehensive Geriatric Assessment (CGA) could predict complications of colorectal cancer (CRC) surgery and identify the problems. So we compared the prognostic value of the CGA with patient characteristics and determined predictive scores. METHODS: A total of 156 patients aged 75 years and older, who underwent surgery for CRC at Osaka University Hospital, were enrolled. Each patient was examined by the CGA prospectively, and all postoperative complications were obtained from the medical records. The CGA included the Barthel Index (BI), Vitality Index, instrumental activities of daily living (iADL), Mini-Mental State Examination (MMSE) and Geriatric Depression Score (GDS). All elements were retrospectively compared in patients with or without postoperative complications, including delirium, surgical site infection and ileus. RESULTS: Overall, postoperative complications developed in 76 patients (48.7%). The BI and MMSE were associated with the incidence of complications, and BI, iADL, MMSE and GDS were significantly related with delirium. Multivariate logistic analysis identified the MMSE as a significant determinant of postoperative complications after adjusting for other determined predictive scores including the prognostic nutritional index and performance status. CONCLUSION: The CGA was a useful predictor of postoperative complications in elderly patients when administered before surgery for CRC. PMID- 27250984 TI - Efficacy of live feedback to improve objectively monitored compliance to prescribed, home-based, exercise therapy-dosage in 15 to 19 year old adolescents with patellofemoral pain- a study protocol of a randomized controlled superiority trial (The XRCISE-AS-INSTRUcted-1 trial). AB - BACKGROUND: Patellofemoral pain is one of the most frequent knee conditions among adolescents with a prevalence of 7 %. Evidence-based treatment consists of patient education combined with hip and quadriceps strengthening. Recent evidence suggests that a large proportion of adolescents does not follow their exercise prescription, performing too few repetitions or too fast below the prescribed time under tension. Live feedback, such as a metronome or exercise games, has previously shown promising results in improving the quality of exercises. The aim of this study is to investigate if live feedback from a sensor (BandCizerTM) and an iPad will improve the ability of adolescents with PFP to perform exercises as prescribed. METHODS: This study is a randomized, controlled, participant-blinded, superiority trial with a 2-group parallel design. Forty 15 to 19 year old adolescents with patellofemoral pain will be randomized to receive either live visual and auditory feedback on time under tension or no feedback on time under tension during a 6-week intervention period. Adolescents will be instructed to perform three elastic band exercises. Feedback will be provided by BandCizerTM and an iPad. The adolescents perform the exercises twice a week unsupervised and once a week during a supervised group training session. The primary outcome will be the mean deviation of the prescribed time under tension per repetition in seconds during the course of the intervention. DISCUSSION: Low compliance is a major problem among adolescents with patellofemoral pain. Providing the adolescents with real time feedback on time under tension from a sensor and an iPad could potentially help the adolescents perform the exercises as prescribed. This may increase the total exercise dosage they receive during treatment which may help improve patient outcomes. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (identifier: NCT02674841 ) on February 4(th) 2016. PMID- 27250986 TI - A53T in a parkinsonian family: a clinical update of the SNCA phenotypes. AB - Approximately 15 % of PD patients with Parkinson Disease (PD) have the familial type and 5-10 % of these are known to have monogenic forms with either an autosomal dominant or a recessive inheritance pattern. Here, we report on a family carrying the A53T SNCA mutation and we review SNCA mutation phenotypes by comparing point mutations within each other as well as with duplication and triplication. PMID- 27250987 TI - Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults. AB - BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016. PMID- 27250989 TI - Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis. AB - It is a challenge to distinguish parathyroid carcinoma (PTCA) from benign parathyroid lesions without recurrence or metastasis. Parafibromin immunohistochemical (IHC) staining had been described for the diagnosis of PTCA. But great variations existed in the reported sensitivity and specificity among different studies. We conducted a meta-analysis to summarize the diagnostic accuracy of parafibromin staining for PTCA. Published studies from Pubmed, Embase, and Cochrane Library were searched using the combination of terms "parafibromin," "CDC73," "HRPT2," and "parathyroid." Pooled sensitivity and specificity with 95 % confidence interval (CI) were calculated and the summary receiver operator characteristic (SROC) curves were constructed. The heterogeneity among included studies was evaluated and possible reasons were explored by meta-regression. A total of 10 studies including 202 patients with PTCA were finally enrolled in this meta-analysis. For parafibromin staining, sensitivity varied from 29 to 100 % (pooled estimate of 68 %; 95 % CI 49-82 %) and specificity ranged from 61 to 100 % (pooled estimate of 95 %; 95 % CI 85-98 %). The AUC for parafibromin staining was 0.91 (95 % CI 0.88-0.93). A significant heterogeneity was observed among included studies. According to meta-regression analysis, the scoring criteria and parafibromin antibody used in IHC were the covariates influencing the sensitivity. And the specificity decreased if atypical parathyroid adenomas were included in the control groups. The specificity of parafibromin staining was satisfactory for diagnosis of PTCA, while the sensitivity was limited. We suggested that a standardized IHC protocol and scoring system criteria should be applied in future studies to improve the diagnostic performance of parafibromin staining. PMID- 27250988 TI - Fall-related activity avoidance in relation to a history of falls or near falls, fear of falling and disease severity in people with Parkinson's disease. AB - BACKGROUND: There is limited knowledge concerning fall-related activity avoidance in people with Parkinson's disease (PD); such knowledge would be of importance for the development of more efficient PD-care and rehabilitation. This study aimed to examine how fall-related activity avoidance relates to a history of self reported falls/near falls and fear of falling (FOF) as well as to disease severity in people with PD. METHODS: Data were collected from 251 (61 % men) participants with PD; their median (min-max) age and PD duration were 70 (45-93) and 8 (1-43) years, respectively. A self-administered postal survey preceded a home visit which included observations, clinical tests and interview-administered questionnaires. Fall-related activity avoidance was assessed using the modified Survey of Activities and Fear of Falling in the Elderly (mSAFFE) as well as by using a dichotomous (Yes/No) question. Further dichotomous questions concerned: the presence of FOF and the history (past 6 months) of falls or near falls, followed by stating the number of incidents. Disease severity was assessed according to the Hoehn and Yahr (HY) stages. RESULTS: In the total sample (n = 251), 41 % of the participants reported fall-related activity avoidance; the median mSAFFE score was 22. In relation to a history of fall, the proportions of participants (p < 0.001) that reported fall-related activity avoidance were: non fallers (30 %), single fallers (50 %) and recurrent fallers, i.e. >= 2 falls (57 %). Among those that reported near falls (but no falls), 51 % (26 out of 51) reported fall-related activity avoidance. Of those that reported FOF, 70 % reported fall-related activity avoidance. Fall-related activity avoidance ranged from 24 % in the early PD-stage (HY I) to 74 % in the most severe stages (HY IV V). CONCLUSIONS: Results indicate that fall-related activity avoidance may be related to a history of self-reported falls/near falls, FOF and disease severity in people with PD. Importantly, fall-related activity avoidance is reported among those that do not fall and already in mild PD-stages (HY I-II). Although further studies are needed, our findings indicate that fall-related activity avoidance needs to be addressed early in order to prevent sedentary behavior and participation restrictions. PMID- 27250990 TI - Prognostic Impact of the Initial Postoperative CA19-9 Level in Patients with Extrahepatic Bile Duct Cancer. AB - BACKGROUND: The aim of this study was to investigate the prognostic impact of the initial serum postoperative CA19-9 levels in patients with extrahepatic bile duct cancer. METHODS: Data of a total of 143 patients of extrahepatic bile duct cancer with elevated preoperative serum CA19-9 levels (>37 U/ml) who underwent surgery with curative intent were reviewed retrospectively. The patients were divided into the "Normalization group" and "Non-normalization group" (initial postoperative serum CA19-9 <=37 and >37 U/ml, respectively), and the clinicopathological factors and survival outcomes in these groups were comparatively analyzed. RESULTS: The cumulative 5-year overall survival (OS) rate and median survival time (MST) were 39.2 % and 42.9 months, respectively, in the Normalization group and 17.9 % and 24.0 months, respectively, in the Non normalization group (P < 0.001). Presence of jaundice, a poorer histological differentiation grade (G3-4), lymph node metastasis, and initial postoperative serum CA19-9 level (>37 U/ml) were significant independent predictors of a poor prognosis on multivariate analysis. CONCLUSION: Non-normalization of the serum CA19-9 level in the initial postoperative phase is a strong predictor of a poor prognosis and is a useful marker to identify patients who would need additional treatments and stricter follow-up. PMID- 27250992 TI - A 13-Year Retrospective Study on Primary Liver Cancer in Cambodia: A Strikingly High Hepatitis C Occurrence among Hepatocellular Carcinoma Cases. AB - OBJECTIVES: Hepatocellular carcinoma (HCC) is the main type of primary liver cancer (PLC) worldwide, but cholangiocarcinoma (CCA) may be predominant in some specific regions of Southeast Asia. The aim of the present study was to delineate a pattern of Cambodian PLC patients attending the Calmette Hospital in the Cambodian capital Phnom Penh. MATERIALS AND METHODS: A total of 553 medical charts diagnosing PLCs from January 2003 to May 2015 were obtained from both the Oncology and Hepato-Gastroenterology Departments of the Calmette Hospital. RESULTS: HCC was the predominant type of PLC recorded, with 511 cases (92.4%), whereas CCA represented merely 7.6% (42 cases) of the overall series. Hepatitis B virus (HBV; 44.3%) and hepatitis C virus (HCV; 43%) infection rates were similar among the HCC patients, while small subsets of CCA patients were infected with HBV (15.4%) or HCV (11.5%). Most HCC (84%) and CCA (73.8%) patients received palliative treatment only. CONCLUSION: The present study indicates that HCC is the main form of primary hepatic neoplasm among PLC patients attending a hospital in Cambodia. HBV and HCV infections represented equivalent burdens and major contributing factors to HCC. Therefore, the implementation of prevention programs for these infectious agents should become a priority for health policy makers in the country. PMID- 27250991 TI - Microbial succession in an inflated lunar/Mars analog habitat during a 30-day human occupation. AB - BACKGROUND: For potential future human missions to the Moon or Mars and sustained presence in the International Space Station, a safe enclosed habitat environment for astronauts is required. Potential microbial contamination of closed habitats presents a risk for crewmembers due to reduced human immune response during long term confinement. To make future habitat designs safer for crewmembers, lessons learned from characterizing analogous habitats is very critical. One of the key issues is that how human presence influences the accumulation of microorganisms in the closed habitat. RESULTS: Molecular technologies, along with traditional microbiological methods, were utilized to catalog microbial succession during a 30-day human occupation of a simulated inflatable lunar/Mars habitat. Surface samples were collected at different time points to capture the complete spectrum of viable and potential opportunistic pathogenic bacterial population. Traditional cultivation, propidium monoazide (PMA)-quantitative polymerase chain reaction (qPCR), and adenosine triphosphate (ATP) assays were employed to estimate the cultivable, viable, and metabolically active microbial population, respectively. Next-generation sequencing was used to elucidate the microbial dynamics and community profiles at different locations of the habitat during varying time points. Statistical analyses confirm that occupation time has a strong influence on bacterial community profiles. The Day 0 samples (before human occupation) have a very different microbial diversity compared to the later three time points. Members of Proteobacteria (esp. Oxalobacteraceae and Caulobacteraceae) and Firmicutes (esp. Bacillaceae) were most abundant before human occupation (Day 0), while other members of Firmicutes (Clostridiales) and Actinobacteria (esp. Corynebacteriaceae) were abundant during the 30-day occupation. Treatment of samples with PMA (a DNA-intercalating dye for selective detection of viable microbial population) had a significant effect on the microbial diversity compared to non-PMA-treated samples. CONCLUSIONS: Statistical analyses revealed a significant difference in community structure of samples over time, particularly of the bacteriomes existing before human occupation of the habitat (Day 0 sampling) and after occupation (Day 13, Day 20, and Day 30 samplings). Actinobacteria (mainly Corynebacteriaceae) and Firmicutes (mainly Clostridiales Incertae Sedis XI and Staphylococcaceae) were shown to increase over the occupation time period. The results of this study revealed a strong relationship between human presence and succession of microbial diversity in a closed habitat. Consequently, it is necessary to develop methods and tools for effective maintenance of a closed system to enable safe human habitation in enclosed environments on Earth and beyond. PMID- 27250993 TI - Construction and evaluation of a modular biofilm-forming chamber for microbial recovery of neodymium and semi-continuous biofilm preparation. Tolerance of Serratia sp.N14 on acidic conditions and neutralized aqua regia. AB - Recovery of neodymium from liquid metallic wastes and scrap leachates is a crucial step for its recycling, which can take place through the immobilized biofilms of Serratia sp. N14. These biofilms are produced in a fermentor vessel with a turnaround time of 10-14 days, which is unacceptable from an economic point of view for an industrial process. This study proposes the construction and evaluation of a modular system, whereby a biofilm-forming chamber is inserted into the continuous biomass outflow of the main chemostat vessel, for an alternative semi-continuous and economic production of biofilm. The activity of the biofilm from the outflow chamber was found to be the same as the one from the main chamber, which was stored in a cold room (4 degrees C), for 9-12 months, depending on a 24 h nucleation step.Moreover, the ability of the biofilm to function in the presence of a leaching agent (aqua regia) or in acidic conditions was also evaluated. The biofilm of the main chamber can remain active even at 50% neutralized aqua regia (pH 3.0), while at acidic conditions, phosphate release of the cells is reduced to 50%. This strain proves to be very tolerant in low pH or high salt concentration solutions. The biofilm produced from the outflow of the main fermentor vessel is of acceptable activity, rather than being disposed. PMID- 27250994 TI - Mesenchymal Stromal/Stem Cells Do Not Ameliorate Experimental Autoimmune Encephalomyelitis and Are Not Detectable in the Central Nervous System of Transplanted Mice. AB - Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from different tissues. Based on their immunomodulatory and neuroprotective functions, MSC-based cell-therapy approaches have been suggested to antagonize inflammatory activity and neuronal damage associated with autoimmune disease of the central nervous system (CNS), for example, multiple sclerosis (MS). Intravenous MSC transplantation was reported to ameliorate experimental autoimmune encephalomyelitis (EAE), the murine model of MS, within days after transplantation. However, systemic distribution patterns and fate of MSCs after administration, especially their potential to migrate into inflammatory lesions within the CNS, remain to be elucidated. This question has of recent become particularly important, since therapeutic infusion of MSCs is now being tested in clinical trials with MS-affected patients. Here, we made use of the established EAE mouse model to investigate migration and therapeutic efficacy of murine bone marrow-derived MSCs. Applying a variety of techniques, including magnetic resonance imaging, immunohistochemistry, fluorescence in-situ hybridization, and quantitative polymerase chain reaction we found no evidence for immediate migration of infused MSC into the CNS of treated mice. Moreover, in contrast to other studies, transplanted MSCs did not ameliorate EAE. In conclusion, our data does not provide substantiation for a relevant migration of infused MSCs into the CNS of EAE mice supporting the hypothesis that potential therapeutic efficacy could be based on systemic effects. Evaluation of possible mechanisms underlying the observed discrepancies in MSC treatment outcomes between different EAE models demands further studies. PMID- 27250995 TI - Resonant Effects in Nanoscale Bowtie Apertures. AB - Nanoscale bowtie aperture antennas can be used to focus light well below the diffraction limit with extremely high transmission efficiencies. This paper studies the spectral dependence of the transmission through nanoscale bowtie apertures defined in a silver film. A realistic bowtie aperture is numerically modeled using the Finite Difference Time Domain (FDTD) method. Results show that the transmission spectrum is dominated by Fabry-Perot (F-P) waveguide modes and plasmonic modes. The F-P resonance is sensitive to the thickness of the film and the plasmonic resonant mode is closely related to the gap distance of the bowtie aperture. Both characteristics significantly affect the transmission spectrum. To verify these numerical results, bowtie apertures are FIB milled in a silver film. Experimental transmission measurements agree with simulation data. Based on this result, nanoscale bowtie apertures can be optimized to realize deep sub wavelength confinement with high transmission efficiency with applications to nanolithography, data storage, and bio-chemical sensing. PMID- 27250996 TI - Disseminated intravascular coagulation. AB - Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by widespread intravascular activation of coagulation that can be caused by infectious insults (such as sepsis) and non-infectious insults (such as trauma). The main pathophysiological mechanisms of DIC are inflammatory cytokine initiated activation of tissue factor-dependent coagulation, insufficient control of anticoagulant pathways and plasminogen activator inhibitor 1-mediated suppression of fibrinolysis. Together, these changes give rise to endothelial dysfunction and microvascular thrombosis, which can cause organ dysfunction and seriously affect patient prognosis. Recent observations have pointed to an important role for extracellular DNA and DNA-binding proteins, such as histones, in the pathogenesis of DIC. The International Society on Thrombosis and Haemostasis (ISTH) established a DIC diagnostic scoring system consisting of global haemostatic test parameters. This scoring system has now been well validated in diverse clinical settings. The theoretical cornerstone of DIC management is the specific and vigorous treatment of the underlying conditions, and DIC should be simultaneously managed to improve patient outcomes. The ISTH guidance for the treatment of DIC recommends treatment strategies that are based on current evidence. In this Primer, we provide an updated overview of the pathophysiology, diagnosis and management of DIC and discuss the future directions of basic and clinical research in this field. PMID- 27250998 TI - Contents: Macromol. Rapid Commun. 11/2016. PMID- 27250997 TI - Photolithography-Based Patterning of Liquid Metal Interconnects for Monolithically Integrated Stretchable Circuits. AB - We demonstrate a new patterning technique for gallium-based liquid metals on flat substrates, which can provide both high pattern resolution (~20 MUm) and alignment precision as required for highly integrated circuits. In a very similar manner as in the patterning of solid metal films by photolithography and lift-off processes, the liquid metal layer painted over the whole substrate area can be selectively removed by dissolving the underlying photoresist layer, leaving behind robust liquid patterns as defined by the photolithography. This quick and simple method makes it possible to integrate fine-scale interconnects with preformed devices precisely, which is indispensable for realizing monolithically integrated stretchable circuits. As a way for constructing stretchable integrated circuits, we propose a hybrid configuration composed of rigid device regions and liquid interconnects, which is constructed on a rigid substrate first but highly stretchable after being transferred onto an elastomeric substrate. This new method can be useful in various applications requiring both high-resolution and precisely aligned patterning of gallium-based liquid metals. PMID- 27250999 TI - Macromol. Rapid Commun. 11/2016. AB - Back Cover: Polymers featuring photoresponsive groups have been exploited as promising drug delivery systems. Light as spatially and temporally controllable external stimulus can be readily tuned and focused to trigger changes in the structure of polymer chains to provide "on-command" drug delivery. A benign synthesis route for a novel controlled polymerization, known as photoinduced electron/energy transfer-reversible addition-fragmentation (PET-RAFT) polymerization, is presented. Further details can be found in the article by A. Bagheri, J. Yeow, H. Arandiyan, J. Xu, C. Boyer,* and M. Limon page 905. PMID- 27251001 TI - A new concordance measure for risk prediction models in external validation settings. AB - Concordance measures are frequently used for assessing the discriminative ability of risk prediction models. The interpretation of estimated concordance at external validation is difficult if the case-mix differs from the model development setting. We aimed to develop a concordance measure that provides insight into the influence of case-mix heterogeneity and is robust to censoring of time-to-event data. We first derived a model-based concordance (mbc) measure that allows for quantification of the influence of case-mix heterogeneity on discriminative ability of proportional hazards and logistic regression models. This mbc can also be calculated including a regression slope that calibrates the predictions at external validation (c-mbc), hence assessing the influence of overall regression coefficient validity on discriminative ability. We derived variance formulas for both mbc and c-mbc. We compared the mbc and the c-mbc with commonly used concordance measures in a simulation study and in two external validation settings. The mbc was asymptotically equivalent to a previously proposed resampling-based case-mix corrected c-index. The c-mbc remained stable at the true value with increasing proportions of censoring, while Harrell's c index and to a lesser extent Uno's concordance measure increased unfavorably. Variance estimates of mbc and c-mbc were well in agreement with the simulated empirical variances. We conclude that the mbc is an attractive closed-form measure that allows for a straightforward quantification of the expected change in a model's discriminative ability due to case-mix heterogeneity. The c-mbc also reflects regression coefficient validity and is a censoring-robust alternative for the c-index when the proportional hazards assumption holds. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27251002 TI - Gamma-irradiated quiescent cells repair directly induced double-strand breaks but accumulate persistent double-strand breaks during subsequent DNA replication. AB - H2AX is expressed at very low levels in quiescent normal cells in vivo and in vitro. Such cells repair DNA double-strand breaks (DSBs) induced by gamma irradiation through a transient stabilization of H2AX. However, the resultant cells accumulate small numbers of irreparable (or persistent) DSBs via an unknown mechanism. We found that quiescent cells that had repaired DSBs directly induced by gamma-rays were prone to accumulate DSBs during the subsequent DNA replication. Unlike directly induced DSBs, secondary DSBs were not efficiently repaired, although Rad51 and 53BP1 were recruited to these sites. H2AX was dramatically stabilized in response to DSBs directly caused by gamma-rays, enabling gammaH2AX foci formation and DSB repair, whereas H2AX was barely stabilized in response to secondary DSBs, in which gammaH2AX foci were small and DSBs were not efficiently repaired. Our results show a pathway that leads to the persistent DSB formation after gamma-irradiation. PMID- 27251003 TI - Effect of 2 Models of Care and Factors Predicting Patients' Adherence to Doctor's Appointment Attendance in Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria. AB - BACKGROUND: Provision of antiretroviral therapy in resource limited settings has put pressure on the available infrastructure. OBJECTIVES: The study examined patients' adherence to Doctor's appointment attendance after an intervention changing the model of care and factors that predicted adherence. METHODS: Observational study was carried out over four years. The model of care was changed in the last year and the effect assessed. SPSS version 15.0 was used for analysis. Predictors of adherence were determined using logistic regression model. RESULTS: Over half 148 (59.7%) of the patients were females, with a mean age of 40.4+/-8.8 years and baseline CD4 cells of 143.5+/-92.7cells/microliters. "Adherence" rates were 51.3% in 2007, 35.9% in 2008 and 14.9% in 2009 giving patients' average adherence to Doctor's appointment attendance of 34.03%. Intervention changing the model of care in 2010 recorded an adherence rate of 93.1%. CONCLUSIONS: The change in model of care greatly improved patients' "adherence". Patients' knowledge of management, adherence, and smoking and drinking habits were identified as statistically significant predictors of adherence. PMID- 27251004 TI - The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations. AB - Even now, only a portion of leukodystrophy patients are correctly diagnosed, though various causative genes have been identified. In the present report, we describe a case of adult-onset leukodystrophy in a woman with ovarian failure. By whole-exome sequencing, a compound heterozygous mutation consisting of NM_020745.3 (AARS2_v001):c.1145C>A and NM_020745.3 (AARS2_v001):c.2255+1G>A was identified. Neither of the mutations has been previously reported, and this is the first report of alanyl-transfer RNA synthetase 2 mutation in Asia. We anticipate that further studies of the molecular basis of leukodystrophy will provide insight into its pathogenesis and hopefully lead to sophisticated diagnostic and treatment strategies. PMID- 27251006 TI - Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients. AB - Several histone deacetylase inhibitors (HDACis) are known to increase Survival Motor Neuron 2 (SMN2) expression for the therapy of spinal muscular atrophy (SMA). We aimed to compare the effects of suberoylanilide hydroxamic acid (SAHA) and Dacinostat, a novel HDACi, on SMN2 expression and to elucidate their acetylation effects on the methylation of the SMN2. Cell-based assays using type I and type II SMA fibroblasts examined changes in transcript expressions, methylation levels and protein expressions. In silico methods analyzed the intermolecular interactions between each compound and HDAC2/HDAC7. SMN2 mRNA transcript levels and SMN protein levels showed notable increases in both cell types, except for Dacinostat exposure on type II cells. However, combined compound exposures showed less pronounced increase in SMN2 transcript and SMN protein level. Acetylation effects of SAHA and Dacinostat promoted demethylation of the SMN2 promoter. The in silico analyses revealed identical binding sites for both compounds in HDACs, which could explain the limited effects of the combined exposure. With the exception on the effect of Dacinostat in Type II cells, we have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene. PMID- 27251008 TI - Highlights from the Current Issue: June 2016. PMID- 27251005 TI - MicroRNA in pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Patients with PDAC are often asymptomatic, and many have lymph node and distant metastases as well as vessel invasion upon diagnosis. Surgery and current chemotherapy have limited efficacy for improving prognosis, which accounts for overall median survival of 8.6 months and a 9.7% 5-year survival rate. MicroRNAs (miRNAs) are attracting increasing attention because of their association with tumour progression. At least 50% of miRNAs that are aberrantly expressed in tumours have important roles as post-transcriptional regulators and exhibit oncogenic or tumour suppressive activities by directly binding to their target messenger RNAs. Various techniques are available to identify miRNAs that are differentially expressed in cancerous vs normal tissues. In this review, we summarise the miRNA profiles of normal pancreatic tissue and cancer tissue of patients with PDACs and characterise the expression of miRNAs associated with tumour progression. Further, we highlight the target genes and signalling pathways of miRNAs that are aberrantly expressed in PDACs. This knowledge may lead to the development of preventive and therapeutic strategies for treating this deadly disease. PMID- 27251007 TI - Survey of motivation to participate in a birth cohort. AB - For a longitudinal prospective cohort study to be successful, participants' motivation to provide information must be maintained. Therefore, this study aimed to identify items that effectively promote participants' motivation. Questionnaires were mailed to 4541 mothers and expectant mothers in Chiba Prefecture, Japan who participated in a nationwide birth cohort. A total of 2387 (52.6%) responses were received. The following items were identified as primary motivating factors among our cohort: "benefits to the participants' children", "monetary compensation" and "contribution to a better future environment". More than 30% of the respondents expressed a lack of understanding regarding the study purpose and requirements for participation. About 14% were concerned about the leakage of personal information, and 13% felt burdened by having to make a long term commitment to the study. Cluster analysis identified four groups, two of which, one with extremely low levels of motivation and the other motivated by only money or goods, lacked an understanding of the study and tended to be concerned about the associated risks and burdens. Participants in these groups were considered to be at a high risk of dropout. Therefore, implementing measures to provide participants with a better understanding of cohort studies could lead to more successful results. PMID- 27251009 TI - New Web-Based Tool for Generating Scattergrams to Report Hearing Results. PMID- 27251010 TI - Concise Review: Stem Cells and Epithelial-Mesenchymal Transition in Cancer: Biological Implications and Therapeutic Targets. AB - Cancer stem cells (CSCs) constitute a small subpopulation of cancer cells with stem-like properties that are able to self-renew, generate differentiated daughter cells, and give rise to heterogeneous tumor tissue. Tumor heterogeneity is a hallmark of cancer and underlies resistance to anticancer therapies and disease progression. The epithelial-mesenchymal transition (EMT) is a reversible phenomenon that is mediated by EMT-inducing transcription factors (EMT-TFs) and plays an important role in normal organ development, wound healing, and the invasiveness of cancer cells. Recent evidence showing that overexpression of several EMT-TFs is associated with stemness in cancer cells has suggested the existence of a link between EMT and CSCs. In this review, we focus on the roles of CSCs and EMT signaling in driving tumor heterogeneity. A better understanding of the dynamics of both CSCs and EMT-TFs in the generation of tumor heterogeneity may provide a basis for the development of new treatment options for cancer patients. Stem Cells 2016;34:1997-2007. PMID- 27251011 TI - A dual-mode turn-on fluorescent BODIPY-based probe for visualization of mercury ions in living cells. AB - A novel turn-on fluorescent 8-amino BODIPY-based probe carrying a thiourea unit as the mercury ion recognition unit has been developed. Due to the cascade reaction processes, consecutive color changes reflecting the electronic absorption and emission responses were observed upon addition of increased concentrations of mercury(ii) ions. The likely sensing mechanism was proposed as mercury ion-promoted cyclization and subsequent hydrolysis. The probe displayed a selective response to mercury ions over other metal ions. Additionally, experiments with living Human Hepatoma SMMC-7721 cells to visualize intracellular mercury ions in biological systems were carried out with the probe. PMID- 27251012 TI - CTG-loaded liposomes as an approach for improving the intestinal absorption of asiaticoside in Centella Total Glucosides. AB - Centella Total Glucosides (CTG),obtained from Centella asiatica (L.), have been shown to possess a multitude of pharmacological activities, however, oral administeration of CTG failed to fulfill their therapeutic potentials due to the low bioavailability. In this study, the author prepared the liposomes encapsulated CTG using the ethanol injection method in order to enhance their intestinal absorption. The average particle size and the polydispersityindex(PDI) of CTG-loaded liposome in a batch are 137.0nm and 0.283, and the CTG-loaded amounts in CTG-loaded liposomes were 0.177mgmL(-1) and the zeta potential of CTG loaded lipsomes is -21.2mV. The TEM images of CTG-loaded lipsomes showed that CTG loaded liposomes are round and maintain high structural integrity, and their DSC thermograms indicated that CTG might be incorporated into the aqueous phase of DPPC to become more stable. The everted rat gut sac model was used to study the absorption characteristic of CTG-loaded solution in rat intestines. The cumulative absorption amount (Q) and the cumulative absorption percentage (P%) of asiaticoside in the CTG-loaded liposome was significantly higher than that in CTG (P<0.05), both the steady-state infiltration rate (Jss, MUgcm(-2)s(-1)) and the permeability coefficient (Papp, cms(-1)) of asiaticoside in CTG-loaded liposomes were significantly higher than those in CTG (P<0.05), which revealed that the liposomes encapsulated CTG can promote the absorption of asiaticoside in the ileum of the rats by enhancing its transmembrane permeability. The above study will provide the experimental evidence and a reference for the development of the oral dosage forms of Centella total glucosides. PMID- 27251013 TI - tDCS effect on cognitive performance in Parkinson's disease. PMID- 27251014 TI - Strategies toward the Total Synthesis of Calyciphylline B-type Alkaloids: A Computational Perspective Aided by DFT Analysis. AB - Herein we describe synthetic efforts toward the total synthesis of calyciphylline B-type alkaloids. In the process, we disclose a detailed DFT study of equilibrium geometries and transition states that explains the stereochemical outcome during the formation of critical intermediates. X-ray crystallographic analysis reveals interesting conformational features in the naturally occurring deoxycalyciphylline B and its synthetic congeners. PMID- 27251015 TI - Fluorescence microscopy as an alternative to electron microscopy for microscale dispersion evaluation of organic-inorganic composites. AB - Inorganic dispersion is of great importance for actual implementation of advanced properties of organic-inorganic composites. Currently, electron microscopy is the most conventional approach for observing dispersion of inorganic fillers from ultrathin sections of organic-inorganic composites at the nanoscale by professional technicians. However, direct visualization of macrodispersion of inorganic fillers in organic-inorganic composites using high-contrast fluorescent imaging method is hampered. Here we design and synthesize a unique fluorescent surfactant, which combines the properties of the aggregation-induced emission (AIE) and amphiphilicity, to image macrodispersion of montmorillonite and layered double hydroxide fillers in polymer matrix. The proposed fluorescence imaging provides a number of important advantages over electron microscope imaging, and opens a new avenue in the development of direct three-dimensional observation of inorganic filler macrodispersion in organic-inorganic composites. PMID- 27251017 TI - Attractiveness of volatiles from different body parts to the malaria mosquito Anopheles coluzzii is affected by deodorant compounds. AB - Mosquitoes display biting preferences among different sites of the human body. In addition to height or convection currents, body odour may play a role in the selection of these biting sites. Previous studies have shown that skin emanations are important host-finding cues for mosquitoes. In this study, skin emanations were collected from armpits, hands and feet; the volatile profiles were analysed and tested for their attractiveness to the malaria mosquito Anopheles coluzzii. Skin emanations collected from armpits were less attractive to An. coluzzii compared to hands or/and feet. The difference may have been caused by deodorant residues, which were found in the armpit samples and not in those of hands and feet. In a subsequent experiment, volunteers were asked to avoid using skincare products for five days, and thereafter, no differences in attractiveness of the body parts to mosquitoes were found. The detected deodorant compound isopropyl tetradecanoate inhibited mosquito landings in a repellent bioassay. It is concluded that the volatiles emanated from different body parts induced comparable levels of attraction in mosquitoes, and that skincare products may reduce a person's attractiveness to mosquitoes. PMID- 27251018 TI - Gross, histologic, and computed tomographic characterization of nonpathological intrascleral cartilage and bone in the domestic goat (Capra aegagrus hircus). AB - OBJECTIVE: To characterize grossly, histologically, and via computed tomography (CT) the appearance of intrascleral cartilage, bone, or both in domestic goats with otherwise normal eyes and to correlate this with age, sex, and breed. ANIMALS STUDIED: Sixty-eight domestic goats (89 eyes). PROCEDURES: Forty-nine formalin-fixed globes from 38 goats underwent high-resolution CT, and gross and light microscopic examination. An additional 40 eyes from 30 goats underwent light microscopy only. Age, breed, and sex of affected goats were retrieved from medical records. RESULTS: Considering all methods of evaluation collectively, cartilage was detected in 42% of eyes (44% of goats) and bone in 11% of eyes (12% of goats); bone was never seen without cartilage. Goats in which bone, cartilage, or both were detected ranged from 0.25 to 13 (median = 3.5) years of age, represented 11 of 12 breeds of the study population, and had a male:female ratio of 11:19. Bone was detected in the eyes of significantly more males (n = 8) than females (n = 2). No sex predilection was noted for cartilage alone. Histology revealed intrascleral chondrocyte-like cells, hyaline cartilage, and islands of lamellar bone. Some regions of bone had central, adipose-rich, marrow-like cavities. CT localized mineralized tissue as adjacent to or partially surrounding the optic nerve head. CONCLUSIONS: This is the first report of intrascleral bone or cartilage in a normal goat and of intrascleral bone in an otherwise normal mammal. The high prevalence of intrascleral cartilage and bone in this study suggests that this finding is normal and likely represents an adaptation in goats. PMID- 27251019 TI - Hybrid nanostructures of well-organized arrays of colloidal quantum dots and a self-assembled monolayer of gold nanoparticles for enhanced fluorescence. AB - Hybrid nanomaterials comprised of well-organized arrays of colloidal semiconductor quantum dots (QDs) in close proximity to metal nanoparticles (NPs) represent an appealing system for high-performance, spectrum-tunable photon sources with controlled photoluminescence. Experimental realization of such materials requires well-defined QD arrays and precisely controlled QD-metal interspacing. This long-standing challenge is tackled through a strategy that synergistically combines lateral confinement and vertical stacking. Lithographically generated nanoscale patterns with tailored surface chemistry confine the QDs into well-organized arrays with high selectivity through chemical pattern directed assembly, while subsequent coating with a monolayer of close packed Au NPs introduces the plasmonic component for fluorescence enhancement. The results show uniform fluorescence emission in large-area ordered arrays for the fabricated QD structures and demonstrate five-fold fluorescence amplification for red, yellow, and green QDs in the presence of the Au NP monolayer. Encapsulation of QDs with a silica shell is shown to extend the design space for reliable QD/metal coupling with stronger enhancement of 11 times through the tuning of QD-metal spatial separation. This approach provides new opportunities for designing hybrid nanomaterials with tailored array structures and multiple functionalities for applications such as multiplexed optical coding, color display, and quantum transduction. PMID- 27251020 TI - Super color purity green quantum dot light-emitting diodes fabricated by using CdSe/CdS nanoplatelets. AB - Colloidal nanoplatelets (NPLs) have recently been introduced as semiconductor emissive materials for the fabrication of quantum dot light-emitting diodes (QLED) on account of their ultra-narrow photoluminescence (PL) linewidth. In this paper, we report a multilayer all solution-processed green QLED based on colloidal CdSe/CdS core/shell NPLs with a narrow PL full-width-at-half-maximum (FWHM) of 12 nm. Our characterization results reveal that this kind of NPL containing QLED exhibit a low operating voltage of 2.25 V and a maximum luminance up to 33 000 cd m(-2), and peak external quantum efficiency (EQE) of 5%, corresponding to 12.5 cd A(-1) in luminance efficiency. Particularly, these devices show ultra-high color purity for electroluminescence (EL) with FWHM of 14 nm. As extremely narrow EL and ultra-pure color is highly attractive in the applications of LED industries, this work signifies the unique potential application of one new class of colloidal core/shell NPLs in achieving bright and efficient LEDs with superior color saturation. PMID- 27251021 TI - Changes in soil organic carbon in croplands subjected to fertilizer management: a global meta-analysis. AB - Cropland soil organic carbon (SOC) is undergoing substantial alterations due to both environmental and anthropogenic changes. Although numerous case studies have been conducted, there remains a lack of quantification of the consequences of such environmental and anthropogenic changes on the SOC sequestration across global agricultural systems. Here, we conducted a global meta-analysis of SOC changes under different fertilizer managements, namely unbalanced application of chemical fertilizers (UCF), balanced application of chemical fertilizers (CF), chemical fertilizers with straw application (CFS), and chemical fertilizers with manure application (CFM). We show that topsoil organic carbon (C) increased by 0.9 (0.7-1.0, 95% confidence interval (CI)) g kg(-1) (10.0%, relative change, hereafter the same), 1.7 (1.2-2.3) g kg(-1) (15.4%), 2.0 (1.9-2.2) g kg(-1) (19.5%) and 3.5 (3.2-3.8) g kg(-1) (36.2%) under UCF, CF, CFS and CFM, respectively. The C sequestration durations were estimated as 28-73 years under CFS and 26-117 years under CFM but with high variability across climatic regions. At least 2.0 Mg ha(-1) yr(-1) C input is needed to maintain the SOC in ~85% cases. We highlight a great C sequestration potential of applying CF, and adopting CFS and CFM is highly important for either improving or maintaining current SOC stocks across all agro-ecosystems. PMID- 27251022 TI - Genomic structure analysis of a set of Oryza nivara introgression lines and identification of yield-associated QTLs using whole-genome resequencing. AB - Oryza nivara, an annual wild AA-genome species of rice, is an important gene pool for broadening the genetic diversity of cultivated rice (O. sativa L.). Towards identifying and utilizing favourable alleles from O. nivara, we developed a set of introgression lines (ILs) by introducing O. nivara segments into the elite indica rice variety 93-11 background through advanced backcrossing and repeated selfing. Using whole-genome resequencing, a high-density genetic map containing 1,070 bin-markers was constructed for the 131 ILs, with an average length of 349 kb per bin. The 131 ILs cover 95% of O. nivara genome, providing a relatively complete genomic library for introgressing O. nivara alleles for trait improvement. Using this high-density bin-map, QTL mapping for 13 yield-related traits was performed and a total of 65 QTLs were detected across two environments. At ~36.9% of detected QTLs, the alleles from O. nivara conferred improving effects on yield-associated traits. Six cloned genes, Sh4/SHA1, Bh4, Sd1, TE/TAD1, GS3 and FZP, colocalised in the peak intervals of 9 QTLs. In conclusion, we developed new genetic materials for exploration and use of beneficial alleles from wild rice and provided a basis for future fine mapping and cloning of the favourable O. nivara-derived QTLs. PMID- 27251025 TI - Can contact allergy to p-phenylenediamine explain the high rates of terpene hydroperoxide allergy? - An epidemiological study based on consecutive patch test results. AB - BACKGROUND: Contact allergy to linalool hydroperoxides (Lin-OOHs) and limonene hydroperoxides (Lim-OOHs) is common. Similarly to what occurs with the terpene hydroperoxides, reactive intermediates formed from p-phenylenediamine (PPD) can cause oxidative modifications of tryptophan residues on proteins in mechanistic studies. OBJECTIVES: To test the hypothesis that patients sensitized to PPD are at increased risk of concomitant reactivity to either of the terpene hydroperoxides, owing to a 'common pathway' of skin protein oxidation. METHODS: A database study of consecutively patch tested eczema patients (n = 3843) from 2012 to 2015, tested concomitantly with PPD, Lim-OOHs and Lin-OOHs, was performed. Associations were examined by level of concordance and odds ratios (ORs) adjusted for age, sex, and contact allergy to fragrance mix I and fragrance mix II. RESULTS: Concomitant reactions to PPD were seen in 2.2% of Lim-OOH-positive patients and in 4.9% of Lin-OOH-positive patients. Neither proportion was higher than expected by chance. No association existed between PPD and Lim-OOH patch test reactivity. In a multiple logistic regression analysis, PPD allergy was associated with an insignificantly increased risk (OR 2.11, 95%CI:0.92-4.80) of a positive patch test reaction to Lin-OOHs. CONCLUSIONS: PPD sensitization cannot explain the high rates of sensitization to Lin-OOHs and/or Lim-OOHs. Contact allergy to oxidized linalool is more strongly associated with fragrance allergy than with PPD allergy. PMID- 27251023 TI - Investigation of an unrecognized large-scale outbreak of Candida parapsilosis sensu stricto fungaemia in a tertiary-care hospital in China. AB - A data analysis of yeast collections from the National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) programme in 2013 revealed a sudden increase in the proportion of Candida parapsilosis complex isolates (n = 98) in one participating hospital (Hospital H). Out of 443 yeast isolates submitted to the CHIF-NET reference laboratory by Hospital H (2010-2014), 212 (47.9%) were identified as C. parapsilosis sensu stricto by sequencing analysis of the internal transcribed spacer region and D1/D2 domain of the 26S rRNA gene. Among the 212 C. parapsilosis sensu stricto isolates, 176 (83.0%) bloodstream-based isolates and 25 isolates from tip cultures of various vascular catheters from 25 patients with candidaemia, were subjected to microsatellite genotyping, and a phylogenetic relationship analysis was performed for 152 isolates. Among the 152 isolates, 45 genotypes (T01 to T45) were identified, and two prevalent genotypes (63.8%) were found: T15 (n = 74, 48.7%) and T16 (n = 23, 15.1%). These two main clones were confined mainly to three different wards of the hospital, and they persisted for 16-25 months and 12-13 months, respectively. The lack of proper coordination between the clinical microbiology laboratory and infection control staff as part of public health control resulted in the failure to timely identify an outbreak, which led to the wide and long-term dissemination of C. parapsilosis sensu stricto in Hospital H. PMID- 27251026 TI - Localized Spoof Surface Plasmons based on Closed Subwavelength High Contrast Gratings: Concept and Microwave-Regime Realizations. AB - In this work, we report the existence of spoof localized surface plasmons (spoof LSPs) arising with closed high contrast gratings (HCGs) at deep subwavelength scales, another platform for field localization at microwave frequencies. The HCGs are in the form of a periodic array of radial dielectric blocks with high permittivity around a metal core supporting spoof-LSPs of transverse magnetic (TM) form. Simulation results validate the phenomenon and a metamaterial approach is also given to capture all the resonant features of this kind of spoof-LSPs. In addition, experimental verification of the existence of spoof-LSPs supported by a three dimensional (3D) HCGs resonance structure in the microwave regime is presented. This work expands the original spoof-LSPs theory and opens up a new avenue for obtaining resonance devices in the microwave frequencies. PMID- 27251027 TI - Prebiotic potential of gum odina and its impact on gut ecology: in vitro and in vivo assessments. AB - The use of prebiotics to escalate certain gut flora is a current aspect of research for effective gut ecology. In the present study we appraise the efficacy of gum odina obtained from the bark of Odina wodier (Anacardiaceae), which is not fully degraded (16%) in the upper GI tract and becomes available to the lower region, as a prebiotic. An in vitro prebiotic activity assay established a quantitative score to describe the extent to which gum odina supports the selective growth of probiotics with a maximum of 5.60 +/- 0.11 for Lactobacillus plantarum MTCC 6160. The polysaccharide, upon fermentation, also liberates lactic acid (0.46 +/- 0.003 mg ml(-1)) and acetic acid (1.03 +/- 0.003 mg ml(-1)). In vivo studies revealed that natural gum selectively stimulates Lactobacillus sp., and eliminates enteric pathogens with a C.F.U. of 384.48 +/- 0.11 and 40.56 +/- 0.17 respectively on the 8(th) day. The changes in the level of beta galactosidase signify maturation of macrophages in the gut environment. It also boosts the immune system by increasing sIgA upon infection from the 5(th) day in the gut, when incorporated into the feed of mice. Moreover an increase in levels of IFNgamma on the 5(th) day also manifest additional protection against various pathogen-induced primary and secondary infections. Thus, gum odina is a potential prebiotic which not only provides nutrition but also improves gut ecology. PMID- 27251028 TI - Development of Core-Shell Nanostructures by In Situ Assembly of Pyridine-Grafted Diblock Copolymer and Transferrin for Drug Delivery Applications. AB - We previously reported the coassembly of various proteins with poly(4 vinylpyridine) (P4VP) to form core-shell nanoparticles (CSNPs). However, P4VP suffers from its cytotoxicity and in vivo toxicity, which prohibit it from many potential biomedical applications. Here, pyridine-grafted diblock copolymer poly(caprolactone-graft-pyridine)-block-poly(caprolactone) [P(CL-g-Py)-b-PCL] was prepared through a combination of ring-opening polymerization and Cu(I) catalyzed azide-alkyne cycloaddition reaction. CSNPs could be readily constructed by the self-assembly of transferrin (Tf) and P(CL-g-Py)-b-PCL, which showed a narrower range of particle sizes, improved stability, and higher loading capacity for anticancer drug doxorubicin (DOX), compared with similar particles prepared from the coassembly of Tf and P4VP. Additionally, the drug-loaded Tf/P(CL-g-Py)-b-PCL CSNPs could effectively target MCF7 cancer cells via the binding of Tf to transferrin receptors (TfR). PMID- 27251029 TI - Development and Reliability Evaluation of the Movement Rating Instrument for Virtual Reality Video Game Play. AB - BACKGROUND: Virtual reality active video games are increasingly popular physical therapy interventions for children with cerebral palsy. However, physical therapists require educational resources to support decision making about game selection to match individual patient goals. Quantifying the movements elicited during virtual reality active video game play can inform individualized game selection in pediatric rehabilitation. OBJECTIVE: The objectives of this study were to develop and evaluate the feasibility and reliability of the Movement Rating Instrument for Virtual Reality Game Play (MRI-VRGP). METHODS: Item generation occurred through an iterative process of literature review and sample videotape viewing. The MRI-VRGP includes 25 items quantifying upper extremity, lower extremity, and total body movements. A total of 176 videotaped 90-second game play sessions involving 7 typically developing children and 4 children with cerebral palsy were rated by 3 raters trained in MRI-VRGP use. Children played 8 games on 2 virtual reality and active video game systems. Intraclass correlation coefficients (ICCs) determined intra-rater and interrater reliability. RESULTS: Excellent intrarater reliability was evidenced by ICCs of >0.75 for 17 of the 25 items across the 3 raters. Interrater reliability estimates were less precise. Excellent interrater reliability was achieved for far reach upper extremity movements (ICC=0.92 [for right and ICC=0.90 for left) and for squat (ICC=0.80) and jump items (ICC=0.99), with 9 items achieving ICCs of >0.70, 12 items achieving ICCs of between 0.40 and 0.70, and 4 items achieving poor reliability (close-reach upper extremity-ICC=0.14 for right and ICC=0.07 for left) and single leg stance (ICC=0.55 for right and ICC=0.27 for left). CONCLUSIONS: Poor video quality, differing item interpretations between raters, and difficulty quantifying the high-speed movements involved in game play affected reliability. With item definition clarification and further psychometric property evaluation, the MRI-VRGP could inform the content of educational resources for therapists by ranking games according to frequency and type of elicited body movements. PMID- 27251030 TI - Knowledge, attitudes, beliefs and practices of construction workers towards tetanus vaccine in Northern Italy. AB - Construction workers (CWs) are both more exposed to tetanus and at higher risk to be inadequately immunized. Our aim was to evaluate tetanus immunization status and knowledge/attitudes towards tetanus vaccination in CWs in Italy. In this field report, the immunization status of 554 unskilled CWs (i.e. labourers). Immunization status was assessed recalling immunization booklets/certificates. Attitudes and knowledge were collected through a standardized questionnaire. In 240/554 CWs, immunization status was inadequate/not documented: in 184 subjects (33.2%), the last vaccination shot was older than 10 years, whereas basal immunization was incomplete in 20 cases, more frequently in foreign-born people (FBP) than in Italian born (IBP) (OR=7.116). In 198 cases (35.7%), an Occupational Physician (OPh) performed last booster, usually with monovalent (T, n=173) vaccine. The main reason for inadequate immunization was having forgotten the periodic booster (148/554; 26.7%), whereas 42 subjects (7.6%) deliberately avoided tetanus vaccine because of personal/religious beliefs, more frequently in FBP than in IBP (OR=3.182). In summary, the prevalence of inadequate immunization status was relatively high (43.4%): the high prevalence of "forgotten boosters" enlightens the key role of OPh in recalling and promoting vaccination policies. Moreover, the inappropriate use of Td vaccine points out the opportunity for educational campaigns in OPh. PMID- 27251031 TI - Chemical composition and biological activities of essential oil from Filifolium sibiricum (L.) Kitam. AB - The essential oil from Filifolium sibiricum (L.) Kitam were extracted using hydrodistillation and GC-MS was used to analyse the essential oil. The main components were espatulenol (8.55%), geranyl acetate (8.03%), caryophyllene oxide (5.47%), calamenene (4.79%), geraniol (4.28%), calamenene (4.53%), geraniol (4.06%), cedrene epoxide (3.23%), myrtenol (3.18%), transgeranylgeranio (3.13%), etc. The essential oil showed intensive inhibitory effects against MCF-7 with IC50 level of 0.78 mg/mL, HepG-2 with IC50 level of 0.44 mg/mL, SKOV-3 with IC50 level of 0.27 mg/mL, BGC-823 with IC50 level of 0.34 mg/mL. In the antibacterial test, the essential oil showed the significant antibacterial activities. The MIC and MBC values were 5.20 and 5.20 mg/mL against Staphylococcus aureus. PMID- 27251032 TI - Asymmetric synthesis and absolute stereochemistry of a labdane-type diterpenoid isolated from the rhizomes of Isodan yuennanensis. AB - The first synthesis of a labdane-type diterpenoid isolated from Isodon yuennanensis was achieved in fourteen steps from commercially available starting material, (+)-sclareolide. The synthesis features the Barton nitrite ester reaction to introduce an oxime at the angular methyl group and the Jones oxidation to construct the lactone segment. By comparison of the optical rotation of our synthetic sample and the natural sample, the absolute stereochemistry of the natural diterpenoid has been determined. PMID- 27251033 TI - Footprintless disruption of prosurvival genes in aneuploid cancer cells using CRISPR/Cas9 technology. AB - CRISPR/Cas9 has emerged as a powerful methodology for the targeted editing of genomic DNA sequences. Nevertheless, the intrinsic inefficiency of transfection methods required to use this technique with cultured cells requires the selection and isolation of successfully modified cells, which invariably subjects the cells to stress. Here we report a workflow that allows the isolation of genomically modified cells, even where loss of functional alleles constitutes a selective disadvantage owing to impaired ability to survive stress. Using targeted disruption of the Id1 and Id3 genes in murine B16-F10 and Ret melanoma cell lines as an example, we show that the method allows for the footprintless isolation of CRISPR/Cas9-modified aneuploid cancer cells. We also provide evidence that serial CRISPR/Cas9 modifications can occur, for example when initial homologous recombination events introduce cryptic PAM sequences, and demonstrate that multiple alleles can be successfully targeted in aneuploid cancer cells. By sequencing individual alleles we also found evidence for CRISPR/Cas9-induced transposable element insertion, albeit at a low frequency. This workflow should have broad application in the functional analysis of prosurvival gene function in cultured cells. PMID- 27251034 TI - Effect of S100A12 and soluble receptor for advanced glycation end products on the occurrence of severe acute pancreatitis. AB - OBJECTIVE: To assess whether serum levels of S100A12 and soluble receptor for advanced glycation end products (sRAGE) could predict the severity of acute pancreatitis (AP). METHODS: We conducted a non-interventional pilot study, including 74 AP patients and 28 healthy volunteers serving as controls. AP patients were further divided into the mild (MAP, n = 22), moderately severe (MSAP, n = 30) and severe (SAP, n = 22) groups. Peripheral blood samples were collected within 72 h after the onset of AP for the determination of S100A12, sRAGE and C-reactive protein (CRP) levels. The acute physiology and chronic health evaluation II (APACHE II) score, Balthazar computed tomography severity index (CTSI) were calculated at admission. RESULTS: S100A12 and sRAGE levels in SAP patient were significantly higher than in controls, MAP and MSAP patients. The receiver operating characteristic (ROC) curve analysis demonstrated the predictive ability of S100A12 [sensitivity 91%, specificity 81%, the area under the ROC curve AUROC 0.9047] and sRAGE (sensitivity 57%, specificity 100%, AUROC 0.8304) for evaluating the severity of AP. S100A12 and sRAGE were correlated with APACHE II and CTSI but not with CRP. This combination of new and traditional indicators had higher accuracy than traditional indicators alone. Specifically, S100A12 and sRAGE were positively correlated with the type of organ failure (respiratory and renal failure) and might distinguish transient from persistent organ failure at admission. CONCLUSION: S100A12 and sRAGE could be used as efficient biomarkers for the early identification of SAP. PMID- 27251035 TI - The mitochondrial kinase PINK1: functions beyond mitophagy. AB - Mutations in the genes encoding the mitochondrial kinase PINK1 and the E3 ubiquitin ligase Parkin cause autosomal recessive Parkinson's disease (PD). Pioneering work in Drosophila melanogaster revealed that the loss of PINK1 or Parkin function causes similar phenotypes including dysfunctional mitochondria. Further research showed that PINK1 can act upstream of Parkin in a mitochondrial quality control pathway to induce removal of damaged mitochondria in a process called mitophagy. Albeit the PINK1/Parkin-induced mitophagy pathway is well established and has recently been elucidated in great detail, its pathophysiological relevance is being debated. Mounting evidence indicates that PINK1 has additional functions, for example, in regulating complex I activity and maintaining neuronal viability in response to stress. Here, we discuss mitophagy dependent and -independent functions of PINK1 and their possible role in PD pathogenesis. Mutations in the PINK1 gene, encoding a mitochondrial kinase, are associated with autosomal recessive Parkinson's disease. In this review, we summarize and discuss the functional roles of PINK1 in maintaining mitochondrial integrity, eliminating damaged mitochondria, and promoting cell survival. This article is part of a special issue on Parkinson disease. PMID- 27251036 TI - Tolerance Induction of Temperature and Starvation with Tricalcium Phosphate on Preservation and Sporulation in Bacillus amyloliquefaciens Detected by Flow Cytometry. AB - The Bacillus species have many applications in the preparation of various enzymes, probiotic, biofertilizer, and biomarkers for which the survival of resting cells and spore formation under different conditions are important. In this study, water and saline along with different mineral substances such as calcium carbonate, calcium phosphate, and silica were used for the detection of survival and preservation of Bacillus amyloliquefaciens. The results showed intensive death of resting cells at 8 degrees C, but significant survival at 28 degrees C after one month. However, preservation by minerals significantly decreased the rate of death and induced sporulation at both the temperatures. The resting cells were maintained at room temperature (about 60 % of the initial population survived after a month) in the presence of tricalcium phosphate. The results showed that temperature has more effect on sporulation compare with starvation. The sporulation in normal saline at 28 degrees C was 70 times more than that at 8 degrees C; meanwhile, addition of tricalcium phosphate increases sporulation by 90 times. Also, the FTIR data showed the interaction of tricalcium phosphate with spores and resting cells. The discrimination of sporulation from non-sporulation state was performed by nucleic acid staining with thiazole orange and detected by flow cytometry. The flow cytometric studies confirmed that the rates of sporulation in pure water were significantly more at 28 degrees C. This is the first report on the detection of bacterial spore with thiazole orange by flow cytometry and also on the interaction of tricalcium phosphate with spores by FTIR analyses. PMID- 27251037 TI - Quantitative metabolomics of the thermophilic methylotroph Bacillus methanolicus. AB - BACKGROUND: The gram-positive bacterium Bacillus methanolicus MGA3 is a promising candidate for methanol-based biotechnologies. Accurate determination of intracellular metabolites is crucial for engineering this bacteria into an efficient microbial cell factory. Due to the diversity of chemical and cell properties, an experimental protocol validated on B. methanolicus is needed. Here a systematic evaluation of different techniques for establishing a reliable basis for metabolome investigations is presented. RESULTS: Metabolome analysis was focused on metabolites closely linked with B. methanolicus central methanol metabolism. As an alternative to cold solvent based procedures, a solvent-free quenching strategy using stainless steel beads cooled to -20 degrees C was assessed. The precision, the consistency of the measurements, and the extent of metabolite leakage from quenched cells were evaluated in procedures with and without cell separation. The most accurate and reliable performance was provided by the method without cell separation, as significant metabolite leakage occurred in the procedures based on fast filtration. As a biological test case, the best protocol was used to assess the metabolome of B. methanolicus grown in chemostat on methanol at two different growth rates and its validity was demonstrated. CONCLUSION: The presented protocol is a first and helpful step towards developing reliable metabolomics data for thermophilic methylotroph B. methanolicus. This will definitely help for designing an efficient methylotrophic cell factory. PMID- 27251038 TI - A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker. AB - BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored. METHODS: We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up. RESULTS: Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution. CONCLUSIONS: These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations. PMID- 27251039 TI - A set of isogenic auxotrophic strains for constructing multiple gene deletion mutants and parasexual crossings in Aspergillus niger. AB - To construct a set of isogenic auxotrophic strains in Aspergillus niger suited for creating multiple gene deletion mutants and executing parasexual crossings, we have combined mutations in genes involved in colour pigmentation (fwnA and olvA) with well-selectable auxotrophic markers (pyrG, nicB, argB, and adeA). All markers, except for the pyrG marker, were introduced by targeted deletion, omitting UV mutagenesis of the strains. Aspergillus oryzae orthologous genes of the argB, nicB, and adeA markers were used as heterologous selection markers, and all markers were shown to complement to respective auxotrophic A. niger mutants. A quadruple auxotrophic marker was further constructed suitable for multiple gene deletions. Genome sequencing of two auxotrophic colour mutants JN3.2 (olvA::pyrG, argB::hygB) and JN6.2 (olvA::pyrG, nicB::hygB) revealed four SNPs between them in non-coding regions, indicating a high level of isogenicity between both strains. The availability of near-isogenic complementary auxotrophic colour mutants facilitates the selection of diploids and the isolation of haploid segregants from the diploid using the parasexual cycle. PMID- 27251040 TI - Analysis of coevolution in nonstructural proteins of chikungunya virus. AB - BACKGROUND: RNA viruses are characterized by high rate of mutations mainly due to the lack of proofreading repair activities associated with its RNA-dependent RNA polymerase (RdRp). In case of arboviruses, this phenomenon has lead to the existence of mixed population of genomic variants within the host called quasi species. The stability of strains within the quasi-species lies on mutations that are positively selected which in turn depend on whether these mutations are beneficial in either or both hosts. Coevolution of amino acids (aa) is one phenomenon that leads to establishment of favorable traits in viruses and leading to their fitness. RESULTS: Fourteen CHIKV clinical samples collected over three years were subjected to RT-PCR, the four non-structural genes amplified and subjected to various genetic analyses. Coevolution analysis showed 30 aa pairs coevolving in nsP1, 23 aa pairs coevolving in nsP2, 239 in nsP3 and 46 aa coevolving pairs in nsP4 when each non-structural protein was considered independently. Further analysis showed that 705 amino acids pairs of the non structural polyproteins coevolved together with a correlation coefficient of >=0.5. Functional relevance of these coevolving amino acids in all the nonstructural proteins of CHIKV were predicted using Eukaryotic Linear Motifs (ELMs) of human. CONCLUSIONS: The present study was undertaken to study co evolving amino acids in the non-structural proteins of chikungunya virus (CHIKV), an important arbovirus. It was observed that several amino acids residues were coevolving and shared common functions. PMID- 27251041 TI - Chromosomal Aberrations in Canine Gliomas Define Candidate Genes and Common Pathways in Dogs and Humans. AB - Spontaneous gliomas in dogs occur at a frequency similar to that in humans and may provide a translational model for therapeutic development and comparative biological investigations. Copy number alterations in 38 canine gliomas, including diffuse astrocytomas, glioblastomas, oligodendrogliomas, and mixed oligoastrocytomas, were defined using an Illumina 170K single nucleotide polymorphism array. Highly recurrent alterations were seen in up to 85% of some tumor types, most notably involving chromosomes 13, 22, and 38, and gliomas clustered into 2 major groups consisting of high-grade IV astrocytomas, or oligodendrogliomas and other tumors. Tumor types were characterized by specific broad and focal chromosomal events including focal loss of the INK4A/B locus in glioblastoma and loss of the RB1 gene and amplification of the PDGFRA gene in oligodendrogliomas. Genes associated with the 3 critical pathways in human high grade gliomas (TP53, RB1, and RTK/RAS/PI3K) were frequently associated with canine aberrations. Analysis of oligodendrogliomas revealed regions of chromosomal losses syntenic to human 1p involving tumor suppressor genes, such as CDKN2C, as well as genes associated with apoptosis, autophagy, and response to chemotherapy and radiation. Analysis of high frequency chromosomal aberrations with respect to human orthologues may provide insight into both novel and common pathways in gliomagenesis and response to therapy. PMID- 27251043 TI - Protective Effects of Forskolin on Behavioral Deficits and Neuropathological Changes in a Mouse Model of Cerebral Amyloidosis. AB - The production of amyloid-beta peptides in the brains of patients with Alzheimer disease (AD) may contribute to memory loss and impairments in social behavior. Here, an efficient adenylate cyclase activator, forskolin, was orally administered by gavage (100 mg/kg body weight) to 5-month-old transgenic APP/PS1 mice, which serve as an animal model of cerebral amyloidosis. Analyses of nest construction, sociability, and immunohistochemical features were used to determine the effects of forskolin treatment. After a relatively short term of treatment (10 days), forskolin-treated transgenic mice showed restored nest construction ability (p < 0.05) and their sociability (p < 0.01). There was a reduction of Abeta plaque deposition in the cortex and in the hippocampus. Furthermore, expression of transforming growth factor beta, glial fibrillary acidic protein, and Iba-1 in the cortex was reduced in the forskolin-treated group, suggesting regulation of the inflammatory response mediated by activated microglia and astrocytes in the brains of the APP/PS1 mice (p < 0.01). Taken together, these findings suggest that forskolin shows neuroprotective effects in APP/PS1 Tg mice and may be a promising drug in the treatment of patients with AD. PMID- 27251044 TI - Transduodenal ampullectomy provides a less invasive technique to cure early ampullary cancer. AB - BACKGROUND: The aim of this study was to evaluate the clinical efficiency of transduodenal ampullectomy (TDA) compared to conventional pancreatoduodenectomy (PD) in patients with early ampullary cancers. METHODS: We carried out a retrospective study by reviewing the medical records of 43 patients with early ampullary cancer who underwent either TDA or PD from January 2001 to December 2014. TDA and PD were performed on 22 patients and 21 patients, respectively. Clinical data, perioperative clinical outcomes and prognosis were evaluated. The median follow-up was 75 (range, 38-143) months. RESULTS: The sensitivity of intraoperative frozen resection was 100 % (4/4) and 94.9 % (37/39) in patients with pTis and pT1 tumors compared to final histologic diagnoses. The 5-year survival rate of patients with early ampullary cancer was 77.3 % in TDA group and 75.9 % in PD group (P = 0.927). Patients with lymph node metastasis presented a shorter 5-year survival rate (P = 0.014). TDA was associated with lower surgical morbidity (P = 0.033), estimated blood loss (P = 0.002), medical cost (P = 0.028) compared to PD. No pancreatic fistula and surgical mortality occurred in TDA group. CONCLUSIONS: TDA could produce satisfactory clinical efficiency in patients fulfilled the following criteria simultaneously: pTis or pT1 stage, tumor size <= 2 cm, without lymph node metastasis. To achieve favorable outcomes, intraoperative frozen section examinations should be reliable and resection margins should be negative. PMID- 27251042 TI - Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers. AB - Exposure to repetitive mild traumatic brain injury (mTBI) is a risk factor for chronic traumatic encephalopathy, which is characterized by patchy deposition of hyperphosphorylated tau aggregates in neurons and astrocytes at the depths of cortical sulci. We developed an mTBI paradigm to explore effects of repetitive concussive-type injury over several months in mice with a human tau genetic background (hTau). Two injuries were induced in the hTau mice weekly over a period of 3 or 4 months and the effects were compared with those in noninjured sham animals. Behavioral and in vivo measures and detailed neuropathological assessments were conducted 6 months after the first injury. Our data confirm impairment in cerebral blood flow and white matter damage. This was accompanied by a 2-fold increase in total tau levels and mild increases in tau oligomers/conformers and pTau (Thr231) species in brain gray matter. There was no evidence of neurofibrillary/astroglial tangles, neuropil threads, or perivascular foci of tau immunoreactivity. There were neurobehavioral deficits (ie, disinhibition and impaired cognitive performance) in the mTBI animals. These data support the relevance of this new mTBI injury model for studying the consequences of chronic repetitive mTBI in humans, and the role of tau in TBI. PMID- 27251045 TI - Niacin esters of chalcones with tumor-selective properties. AB - Novel series of niacin esters of chalcones 2, 4 and 6 were designed as antineoplastic agents that have the potential to release the chemoprotectant niacin. These enones are cytotoxic to human CD4(+ )T-lymphocyte Molt 4/C8 and CEM and murine leukemia L1210 cells. Quantitative structure-activity relationship (QSAR) studies of the biodata in series 4 revealed that cytotoxic potency was enhanced by placing electron-repelling groups in one of the aryl rings. The compounds are lethal to HL-60, HSC-2, HSC-3 and HSC-4 neoplasms but less toxic to nonmalignant hepatocyte growth factor, hematopoietic progenitor cell and human periodontal ligament fibroblast cells. Hence, the compounds display tumor selective toxicity. These chalcones are well tolerated in mice and no overt toxicity was noted. The results establish that in general the compounds in series 2, 4 and 6 have positive characteristics which warrant further studies. PMID- 27251046 TI - Posterior fossa decompression with and without duraplasty for the treatment of Chiari malformation type I-a systematic review and meta-analysis. AB - The treatment of Chiari malformation type 1 (CM-I) with posterior fossa decompression without (PFD) or with duraplasty (PFDD) is controversial. Our aim is to compare the clinical outcome between the two methods for the treatment of CM-I. In this paper, the authors report a systematic review and meta-analysis of operation time, clinical improvement, and complications of PFD compared with PFDD for the treatment of CM-I. Randomized or non-randomized controlled trials of PFD and PFDD were considered for inclusion. Twelve published reports of eligible studies involving 841participants meet the inclusion criteria. There is significant difference in the operative time [mean difference = -74.63, 95 % CI ( 83.02, -66.25), p < 0.05] in favor of PFD compared with PFDD. There is significant difference in overall complication rates [mean difference = 0.34, 95 % CI (0.19, 0.60), p < 0.05] and rates of CSF leak [mean difference = 0.24, 95 % CI (0.07, 0.78), p < 0.05] in favor of PFD groups. However, there is significant difference in the clinical improvement rate in favor of the PFDD group [mean difference = 0.85, 95 % CI (0.73, 0.99), p < 0.05]. Although PFDD is related with longer operation time and higher CSF leak rate, it can still be considered as a preferable treatment option for most CM-I patients for its higher improvement rate. More evidence from advanced multi-center studies are needed to provide illumination for the surgical decision making of CM-I. PMID- 27251047 TI - A method for estimating gestational age of fetal remains based on long bone lengths. AB - The estimation of gestational age (GA) in fetal human remains is important in forensic settings, particularly to assess fetal viability, in addition to often being the only biological profile parameter that can be assessed with some accuracy for non-adults. The length of long bone diaphysis is one of the most frequently used methods for fetal age estimation. The main objective of this study was to present a simple and objective method for estimating GA based on the measurements of the diaphysis of the femur, tibia, fibula, humerus, ulna, and radius. Conventional least squares regression equations (classical and inverse calibration approaches) and quick reference tables were generated. A supplementary objective was to compare the performance of the new formulae against previously published models. The sample comprised 257 fetuses (136 females and 121 males) with known GA (between 12 and 40 weeks) and was selected based on clinical and pathological information. All measurements were performed on radiographic images acquired in anonymous clinical autopsy records from spontaneous and therapeutic abortions in two Portuguese hospitals. The proposed technique is straightforward and reproducible. The models for the GA estimation are exceedingly accurate and unbiased. Comparisons between inverse and classical calibration show that both perform exceptionally well, with high accuracy and low bias. Also, the newly developed equations generally outperform earlier methods of GA estimation in forensic contexts. Quick reference tables for each long bone are now available. The obtained models for the estimation of gestational age are of great applicability in forensic contexts. PMID- 27251048 TI - Differences that matter: developing critical insights into discourses of patient centeredness. AB - Patient-centeredness can be considered a popular, and at the same time "fuzzy", concept. Scientists have proposed different definitions and models. The present article studies scientific publications that discuss the meaning of patient centeredness to identify different "discourses" of patient-centeredness. Three discourses are presented; the first is labelled as "caring for patients", the second as "empowering patients" and the third as "being responsive". Each of these discourses has different things to say about (a) the why of patient centeredness; (b) the patient's identity; (c) the role of the healthcare professional; (d) responsibilities for medical decision-making, and (e) the role of health information. This article compares and contrasts the discourses in ways that allow us to see differences that matter for practitioners in healthcare. On the basis of a relational constructionist philosophy, it is argued that discursive diversity is both an inevitable and a potentially valuable aspect of conversations in healthcare. We are therefore invited to center the challenge of dealing with diversity in productive ways. This article ends with a discussion of the practical implications of the discourse analysis for projects that aim to make healthcare more patient-centered. Debates on patient-centered "Health Information Exchange" are used to explain the need for a recognition of different discourses of patient-centeredness and a reflexive stance towards them. PMID- 27251049 TI - Authors' reply to Seemungal and Bolland and colleagues. PMID- 27251050 TI - Molecular characteristics of a novel strain of canine minute virus associated with hepatitis in a dog. AB - A 5-year-old female Yorkshire terrier dog died a few days following hernia and ovariohysterectomy surgeries. Necropsy performed on the dog revealed that the surgeries were not the cause of death; however, degenerative viral hepatitis, showing intranuclear inclusion bodies in hepatic cells, was observed in histopathologic examination. Several diagnostic methods were used to screen for the cause of disease, and minute virus of canines (MVC) was detected in all parenchymal organs, including the liver. Other pathogens that may cause degenerative viral hepatitis were not found. Infection with MVC was confirmed by in situ hybridization, which revealed the presence of MVC nucleic acid in the liver tissue of the dog. Through sequencing and phylogenetic analysis of the nearly complete genome sequence, the strain was found to be distinct from other previously reported MVC strains. These results indicate that this novel MVC strain might be related to degenerative viral hepatitis in dogs. PMID- 27251051 TI - Cutaneous Adverse Events in the Randomized, Double-Blind, Active-Comparator DECIDE Study of Daclizumab High-Yield Process Versus Intramuscular Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis. AB - INTRODUCTION: Cutaneous adverse events (AEs) have been observed in clinical studies of daclizumab high-yield process (HYP) in relapsing-remitting multiple sclerosis (RRMS). Here, we report cutaneous AEs observed in the randomized, double-blind, active-comparator DECIDE study (ClinicalTrials.gov identifier, NCT01064401). METHODS: DECIDE was a randomized, double-blind, active-controlled phase 3 study of daclizumab HYP 150 mg subcutaneous every 4 weeks versus interferon (IFN) beta-1a 30 mcg intramuscular (IM) once weekly in RRMS. Treatment emergent AEs were classified and recorded by investigators. Investigators also assessed the severity of each AE, and whether it met the criteria for a serious AE. Cutaneous AEs were defined as AEs coded to the Medical Dictionary for Regulatory Activities System Organ Class of skin and subcutaneous tissue disorders. The incidence, severity, onset, resolution, and management of AEs were analyzed by treatment group. RESULTS: Cutaneous AEs were reported in 37% of daclizumab HYP-treated patients and 19% of IFN beta-1a-treated patients. The most common investigator-reported cutaneous AEs with daclizumab HYP were rash (7%) and eczema (4%). Most patients with cutaneous AEs remained on treatment (daclizumab HYP, 81%; IM IFN beta-1a, 90%) and had events that were mild or moderate (94% and 98%) and subsequently resolved (78% and 82%). Most patients with cutaneous AEs did not require treatment with corticosteroids or were treated with topical corticosteroids (daclizumab HYP, 73%; IM IFN beta-1a, 81%). Serious cutaneous AEs were reported in 14 (2%) daclizumab HYP patients and one (<1%) IM IFN beta-1a patient. CONCLUSION: There was an increased risk of cutaneous AEs with daclizumab HYP. While physicians should be aware of the potential for serious cutaneous AEs, the typical cutaneous AEs were mild-to-moderate in severity, manageable, and resolved over time. FUNDING: Biogen and AbbVie Biotherapeutics Inc. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01064401. PMID- 27251052 TI - Effectiveness of the Home Based Life Saving Skills training by community health workers on knowledge of danger signs, birth preparedness, complication readiness and facility delivery, among women in Rural Tanzania. AB - BACKGROUND: In spite of government efforts, maternal mortality in Tanzania is currently at more than 400 per 100,000 live births. Community-based interventions that encourage safe motherhood and improved health-seeking behaviour through acquiring knowledge on the danger signs and improving birth preparedness, and, ultimately, reduce maternal mortality, have been initiated in different parts of low-income countries. Our aim was to evaluate if the Home Based Life Saving Skills education by community health workers would improve knowledge of danger signs, birth preparedness and complication readiness and facility-based deliveries in a rural community in Tanzania. METHODS: A quasi-experimental study design was used to evaluate the effectiveness of Home Based Life Saving Skills education to pregnant women and their families through a community intervention. An intervention district received training with routine care. A comparison district continued to receive routine antenatal care. A structured household questionnaire was used in order to gather information from women who had delivered a child within the last two years before the intervention. This questionnaire was used in both the intervention and comparison districts before and after the intervention. The net intervention effect was estimated using the difference between the differences in the intervention and control districts at baseline and endline. RESULTS: A total of 1,584 and 1,486 women were interviewed at pre-intervention and post intervention, respectively. We observed significant improvement of knowledge of three or more danger signs during pregnancy (15.2 % vs. 48.1 %) with a net intervention effect of 29.0 % (95 % CI: 12.8-36.2; p < .0001) compared to the comparison district. There was significant effect on the knowledge of three or more danger signs during childbirth (15.3 % vs. 43.1 %) with a net intervention effect of 18.3 % (95 % CI: 11.4-25.2; p < .0001) and postpartum for those mentioning three or more of the signs (8.8 % vs. 19.8 %) with net effect of 9.4 % (95 % CI: 6.4-15.7; p < .0001). Birth preparedness practice improved for those who made more than three actions (20.8 vs. 35.3 %) with a net intervention effect of 10.3 % (95 % CI: 10.3-20.3; p < .0001) between the intervention and control district at pre-intervention and post intervention. Utilisation of antenatal care with four visits improved significantly (43.4 vs. 67.8 %) with net effect of 25.3 % (95 % CI: 16.9-33.2; p < .0001), use of facility delivery improved in the intervention area (75.6 vs. 90.2 %; p = 0.0002) but there was no significant net effect 11.5 % (95 % CI: -5.1-39.6; p = 0.123) compared to comparison district. CONCLUSION: This study shows that a community based intervention employing community health workers as teachers in delivering Home Based Life Saving Skills program to pregnant women and their families improved their knowledge of danger signs during pregnancy, childbirth and postpartum, preparedness for childbirth and increased deliveries at health facilities which employ skilled health workers in this rural community. PMID- 27251053 TI - Sex-Based Differences in Smgc Expression in the Submandibular Gland of C57BL/6 Mice. AB - OBJECTIVE: The decrease in female hormone levels at menopause affects whole-body homeostasis. Various therapies including hormone therapy and treatment with herbal supplements are available to improve menopausal symptoms. However, a method for evaluating their effectiveness has not been established. We sought to identify useful biomarkers to assess therapy efficacy. METHODS: We searched for salivary proteins affected by changes in female hormone levels in mouse submandibular glands. RESULTS: The expression of submandibular gland protein C (Smgc) was decreased following ovariectomy, while the expression of the alternative splicing transcript t-Smgc was increased. Notably, Smgc expression increased following beta-estradiol administration, and was barely detectable in the submandibular glands of male mice. CONCLUSION: The results suggest that Smgc expression may be estrogen dependent. Moreover, changes in the SMGC protein amount in the saliva were in accordance with those in mRNA expression in the submandibular gland. Our findings suggest that salivary proteins have potential as markers for evaluating therapies for menopausal symptoms. PMID- 27251054 TI - Intravitreal vascular endothelial growth factor (VEGF) inhibitor injection in unrecognised early pregnancy. AB - The use of intravitreal vascular endothelial growth factor (VEGF) inhibitor medications has widened considerably to include indications affecting females of reproductive age. Our patient was inadvertently exposed to bevacizumab within the first trimester when placental growth and fetal organogenesis take place and patient suffered pregnancy loss. There is insufficient information to suggest that such use is safe, nor is there definitive evidence to suggest that it causes harm. We advise that ophthalmologists discuss pregnancy with women of childbearing age undergoing intraocular anti-VEGF injections and in pregnant woman counselling is needed to explain the potential risks and benefits. PMID- 27251055 TI - An evaluation of alternative selection indexes for a non-linear profit trait approaching its economic optimum. AB - This study used simulation to evaluate the performance of alternative selection index configurations in the context of a breeding programme where a trait with a non-linear economic value is approaching an economic optimum. The simulation used a simple population structure that approximately mimics selection in dual purpose sheep flocks in New Zealand (NZ). In the NZ dual purpose sheep population, number of lambs born is a genetic trait that is approaching an economic optimum, while genetically correlated growth traits have linear economic values and are not approaching any optimum. The predominant view among theoretical livestock geneticists is that the optimal approach to select for nonlinear profit traits is to use a linear selection index and to update it regularly. However, there are some nonlinear index approaches that have not been evaluated. This study assessed the efficiency of the following four alternative selection index approaches in terms of genetic progress relative to each other: (i) a linear index, (ii) a linear index updated regularly, (iii) a nonlinear (quadratic) index, and (iv) a NLF index (nonlinear index below the optimum and then flat). The NLF approach does not reward or penalize animals for additional genetic merit beyond the trait optimum. It was found to be at least comparable in efficiency to the approach of regularly updating the linear index with short (15 year) and long (30 year) time frames. The relative efficiency of this approach was slightly reduced when the current average value of the nonlinear trait was close to the optimum. Finally, practical issues of industry application of indexes are considered and some potential practical benefits of efficient deployment of a NLF index in highly heterogeneous industries (breeds, flocks and production environments) such as in the NZ dual purpose sheep population are discussed. PMID- 27251056 TI - Detailed Lymph Node Sectioning of Papillary Thyroid Carcinoma Specimen Increases the Number of pN1a Patients. AB - Papillary thyroid carcinoma (PTC) is a common endocrine malignancy, frequently presenting with lymph node metastasis at the time of diagnosis. Lymph node staging (N) partly determines treatment, follow-up, and prognosis. Since 2011, our institution has employed a more comprehensive histopathological work-up of lymph nodes in patients with PTC. We sought to retrospectively determine the value of serial lymph node level sectioning in PTCs with negative preoperative lymph node status (pN0) as a method to increase the sensitivity of detecting metastatic disease. We included all patients that underwent thyroidectomy and central neck dissection and subsequent comprehensive lymph node level sectioning due to PTC with an initial pN0 status between the years 2011 and 2015 at our institution. Sixty-seven cases of PTC with a median of 10 metastatic free lymph nodes identified per case were included. After serial lymph node sectioning of the central compartment, 11 cases (16 %) revealed lymph node metastasis, six of which (55 %) presented with a small primary tumor (<20 mm, T1). Of all T1 tumors with initial pN0 status, 18 % (T1a) and 9 % (T1b) reached a pN1 stage after comprehensive lymph node sectioning. Cases with altered lymph node status had a median of 15 identified lymph nodes as compared to ten in cases that remained negative. We conclude that comprehensive lymph node sectioning increased the sensitivity of detecting metastases in PTC and altered the pathological TNM staging (pTNM) for a significant number of patients. Although of limited prognostic significance, the method should be considered as an adjunct tool when assessing lymph node status of PTC as a part of the routine histological work-up to ensure an accurate cancer staging. PMID- 27251059 TI - An investigation on the structure, spectroscopy and thermodynamic aspects of Br2((-))(H2O)n clusters using a conjunction of stochastic and quantum chemical methods. AB - In this work we obtained global as well as local structures of Br2((-))(H2O)n clusters for n = 2 to 6 followed by the study of IR-spectral features and thermochemistry for the structures. The way adopted by us to obtain structures is not the conventional one used in most cases. Here we at first generated excellent quality pre-optimized structures by exploring the suitable empirical potential energy surface using stochastic optimizer simulated annealing. These structures are then further refined using quantum chemical calculations to obtain the final structures, and spectral and thermodynamic features. We clearly showed that our approach results in very quick and better convergence which reduces the computational cost and obviously using the strategy we are able to get one [i.e. global] or more than one [i.e. global and local(s)] energetically lower structures than those which are already reported for a given cluster size. Moreover, IR-spectral results and the evolutionary trends in interaction energy, solvation energy and vertical detachment energy for global structures of each size have also been presented to establish the utility of the procedure employed. PMID- 27251057 TI - Systematic analysis of the molecular mechanism underlying atherosclerosis using a text mining approach. AB - BACKGROUND: Atherosclerosis is one of the common health threats all over the world. It is a complex heritable disease that affects arterial blood vessels. Chronic inflammatory response plays an important role in atherogenesis. There has been little success in fully identifying functionally important genes in the pathogenesis of atherosclerosis. RESULTS: In the present study, we performed a systematic analysis of atherosclerosis-related genes using text mining. We identified a total of 1312 genes. Gene ontology (GO) analysis revealed that a total of 35 terms exhibited significance (p < 0.05) as overrepresented terms, indicating that atherosclerosis invokes many genes with a wide range of different functions. Pathway analysis demonstrated that the most highly enriched pathway is the Toll-like receptor signaling pathway. Finally, through gene network analysis, we prioritized 48 genes using the hub gene method. CONCLUSIONS: Our study provides a valuable resource for the in-depth understanding of the mechanism underlying atherosclerosis. PMID- 27251058 TI - Inadequate Systems to Support Breast and Cervical Cancer Screening in Primary Care Practice. AB - BACKGROUND: Despite substantial resources devoted to cancer screening nationally, the availability of clinical practice-based systems to support screening guidelines is not known. OBJECTIVE: To characterize the prevalence and correlates of practice-based systems to support breast and cervical cancer screening, with a focus on the patient-centered medical home (PCMH). DESIGN: Web and mail survey of primary care providers conducted in 2014. The survey assessed provider (gender, training) and facility (size, specialty training, physician report of National Committee for Quality Assurance (NCQA) PCMH recognition, and practice affiliation) characteristics. A hierarchical multivariate analysis clustered by clinical practice was conducted to evaluate characteristics associated with the adoption of practice-based systems and technology to support guideline-adherent screening. PARTICIPANTS: Primary care physicians in family medicine, general internal medicine, and obstetrics and gynecology, and nurse practitioners or physician assistants from four clinical care networks affiliated with PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium research centers. MAIN MEASURES: The prevalence of routine breast cancer risk assessment, electronic health record (EHR) decision support, comparative performance reports, and panel reports of patients due for routine screening and follow-up. KEY RESULTS: There were 385 participants (57.6 % of eligible). Forty-seven percent (47.0 %) of providers reported NCQA recognition as a PCMH. Less than half reported EHR decision support for breast (48.8 %) or cervical cancer (46.2 %) screening. A minority received comparative performance reports for breast (26.2 %) or cervical (19.7 %) cancer screening, automated reports of patients overdue for breast (18.7 %) or cervical (16.4 %) cancer screening, or follow-up of abnormal breast (18.1 %) or cervical (17.6 %) cancer screening tests. In multivariate analysis, reported NCQA recognition as a PCMH was associated with greater use of comparative performance reports of guideline adherent breast (OR 3.23, 95 % CI 1.58-6.61) or cervical (OR 2.56, 95 % CI 1.32 4.96) cancer screening and automated reports of patients overdue for breast (OR 2.19, 95 % CI 1.15-41.7) or cervical (OR. 2.56, 95 % CI 1.26-5.26) cancer screening. CONCLUSIONS: Providers lack systems to support breast and cervical cancer screening. Practice transformation toward a PCMH may support the adoption of systems to achieve guideline-adherent cancer screening in primary care settings. PMID- 27251060 TI - Sex of co-twin affects the in vitro developmental competence of oocytes derived from 6- to 8-week-old lambs. AB - Several intrinsic factors (age, genotype, liveweight) influence the reliability of juvenile in vitro fertilisation embryo transfer (JIVET) programs. Limited evidence indicates that variability between lambs is reduced in twin-born lambs. We examined the impact of birth type (single, twin, triplet) and sex of the co twin (with age, birthweight and liveweight as covariates) on JIVET outcomes. Birth type did not influence any parameter studied. However, blastocysts produced, as a percentage of embryos cleaved or total cumulus-oocyte complexes collected, was higher (P<0.05) for females born with a female co-twin (67.0+/ 6.1, 57.5+/-6.0 respectively) compared with those born with a male co-twin (26.9+/-6.5, 22.3+/-6.2 respectively; least-square mean+/-s.e.m.). Blastocyst rates for lambs born with a male co-twin did not differ significantly from lambs born either as singles (39.5+/-6.7%, 34.6+/-6.5% respectively) or triplets (43.1+/-10.6%, 36.5+/-10.3% respectively). Other parameters were not influenced by sex of the co-twin. These results are indicative of an enhancement effect of the female co-twin on oocyte development. From a practical perspective, selecting lambs for a JIVET program based on litter size and sex of the co-twin is warranted. PMID- 27251061 TI - Grainyhead-like 2 inhibits the coactivator p300, suppressing tubulogenesis and the epithelial-mesenchymal transition. AB - Developmental morphogenesis and tumor progression require a transient or stable breakdown of epithelial junctional complexes to permit programmed migration, invasion, and anoikis resistance, characteristics endowed by the epithelial mesenchymal transition (EMT). The epithelial master-regulatory transcription factor Grainyhead-like 2 (GRHL2) suppresses and reverses EMT, causing a mesenchymal-epithelial transition to the default epithelial phenotype. Here we investigated the role of GRHL2 in tubulogenesis of Madin-Darby canine kidney cells, a process requiring transient, partial EMT. GRHL2 was required for cystogenesis, but it suppressed tubulogenesis in response to hepatocyte growth factor. Surprisingly, GRHL2 suppressed this process by inhibiting the histone acetyltransferase coactivator p300, preventing the induction of matrix metalloproteases and other p300-dependent genes required for tubulogenesis. A 13 amino acid region of GRHL2 was necessary for inhibition of p300, suppression of tubulogenesis, and interference with EMT. The results demonstrate that p300 is required for partial or complete EMT occurring in tubulogenesis or tumor progression and that GRHL2 suppresses EMT in both contexts through inhibition of p300. PMID- 27251062 TI - Tetrahymena Poc1 ensures proper intertriplet microtubule linkages to maintain basal body integrity. AB - Basal bodies comprise nine symmetric triplet microtubules that anchor forces produced by the asymmetric beat pattern of motile cilia. The ciliopathy protein Poc1 stabilizes basal bodies through an unknown mechanism. In poc1? cells, electron tomography reveals subtle defects in the organization of intertriplet linkers (A-C linkers) that connect adjacent triplet microtubules. Complete triplet microtubules are lost preferentially near the posterior face of the basal body. Basal bodies that are missing triplets likely remain competent to assemble new basal bodies with nine triplet microtubules, suggesting that the mother basal body microtubule structure does not template the daughter. Our data indicate that Poc1 stabilizes basal body triplet microtubules through linkers between neighboring triplets. Without this stabilization, specific triplet microtubules within the basal body are more susceptible to loss, probably due to force distribution within the basal body during ciliary beating. This work provides insights into how the ciliopathy protein Poc1 maintains basal body integrity. PMID- 27251064 TI - Regional Differences in Frequency of Warfarin Therapy and Thromboembolism in Japanese Patients With Non-Valvular Atrial Fibrillation - Analysis of the J RHYTHM Registry. AB - BACKGROUND: The proportion of patients with atrial fibrillation (AF) treated with anticoagulation varies from country to country. In Japan, little is known about regional differences in frequency of warfarin use or prognosis among patients with non-valvular AF (NVAF). METHODS AND RESULTS: In J-RHYTHM Registry, the number of patients recruited from each of 10 geographic regions of Japan was based on region population density. A total of 7,406 NVAF patients were followed up prospectively for 2 years. At baseline, significant differences in various clinical characteristics including age, sex, type of AF, comorbidity, and CHADS2score, were detected among the regions. The highest mean CHADS2score was recorded in Shikoku. Frequency of warfarin use differed between the regions (P<0.001), with lower frequencies observed in Hokkaido and Shikoku. Baseline prothrombin time international normalized ratio differed slightly but significantly between the regions (P<0.05). On univariate analysis, frequency of thromboembolic events differed among the regions (P<0.001), with the highest rate seen in Shikoku. An inverse correlation was detected between frequency of thromboembolic and of major hemorrhagic events (P=0.062). On multivariate analysis, region emerged as an independent risk for thromboembolism. CONCLUSIONS: Thromboembolic risk, frequency of warfarin use, and intensity and quality of warfarin treatment differed significantly between geographic regions of Japan. Region was found to be an independent predictor of thromboembolic events. (Circ J 2016; 80: 1548-1555). PMID- 27251063 TI - The role of the dynein light intermediate chain in retrograde IFT and flagellar function in Chlamydomonas. AB - The assembly of cilia and flagella depends on the activity of two microtubule motor complexes, kinesin-2 and dynein-2/1b, but the specific functions of the different subunits are poorly defined. Here we analyze Chlamydomonas strains expressing different amounts of the dynein 1b light intermediate chain (D1bLIC). Disruption of D1bLIC alters the stability of the dynein 1b complex and reduces both the frequency and velocity of retrograde intraflagellar transport (IFT), but it does not eliminate retrograde IFT. Flagellar assembly, motility, gliding, and mating are altered in a dose-dependent manner. iTRAQ-based proteomics identifies a small subset of proteins that are significantly reduced or elevated in d1blic flagella. Transformation with D1bLIC-GFP rescues the mutant phenotypes, and D1bLIC-GFP assembles into the dynein 1b complex at wild-type levels. D1bLIC-GFP is transported with anterograde IFT particles to the flagellar tip, dissociates into smaller particles, and begins processive retrograde IFT in <2 s. These studies demonstrate the role of D1bLIC in facilitating the recycling of IFT subunits and other proteins, identify new components potentially involved in the regulation of IFT, flagellar assembly, and flagellar signaling, and provide insight into the role of D1bLIC and retrograde IFT in other organisms. PMID- 27251066 TI - Effect of Aging on Fractional Flow Reserve - Hyperemic Index Fractional Flow Reserve May Not Be Sufficient to Reveal the Whole Picture of Coronary Circulation. PMID- 27251067 TI - Self-Assembled 3D Flower-Like Nickel Hydroxide Nanostructures and Their Supercapacitor Applications. AB - Three-dimensional (3D) nanostructures have attracted considerable attention because of their high surface areas and unique properties which gives outstanding performance in catalysis and energy storage applications. This paper proposes the growth mechanism of 3D flower-like beta-Ni(OH)2 constructed through a two dimensional sheet framework using a one-step oleylamine-assisted solvothermal approach, where oleylamine acts as the surfactant, co-solvent, stabilizer, and reducing agent. A detailed examination of the product morphology after various reaction times suggested that the self-assembly of flower occurs through a mechanism involving nucleation, Ostwald ripening, and recrystallization. The associated characterization revealed it to be pure beta-Ni(OH)2 without any sign of contamination. The effect of the morphology (sheet to 3D flower-like beta Ni(OH)2) on the electrochemical supercapacitive behavior was assessed by cyclic voltammetry and galvanostatic charge-discharge tests. The results showed that 3D flower-like beta-Ni(OH)2 exhibited better specific capacitance of ~1567 F g(-1) at a current density of 1 A g(-1) and retained ~25% capacitance at a high current density of 10 A g(-1) compared to the other reference materials. The superior electrochemical properties of the 3D flower-like beta-Ni(OH)2 originate from their large specific surface area and unique structure. PMID- 27251065 TI - Rho Kinases and Cardiac Remodeling. AB - Hypertensive cardiac remodeling is characterized by left ventricular hypertrophy and interstitial fibrosis, which can lead to heart failure with preserved ejection fraction. The Rho-associated coiled-coil containing kinases (ROCKs) are members of the serine/threonine protein kinase family, which mediates the downstream effects of the small GTP-binding protein RhoA. There are 2 isoforms: ROCK1 and ROCK2. They have different functions in different types of cells and tissues. There is growing evidence that ROCKs contribute to the development of cardiovascular diseases, including cardiac fibrosis, hypertrophy, and subsequent heart failure. Recent experimental studies using ROCK inhibitors, such as fasudil, have shown the benefits of ROCK inhibition in cardiac remodeling. Mice lacking each ROCK isoform also exhibit reduced myocardial fibrosis in a variety of pathological models of cardiac remodeling. Indeed, clinical studies with fasudil have suggested that ROCKs could be potential novel therapeutic targets for cardiovascular diseases. In this review, we summarize the current understanding of the roles of ROCKs in the development of cardiac fibrosis and hypertrophy and discuss their therapeutic potential for deleterious cardiac remodeling. (Circ J 2016; 80: 1491-1498). PMID- 27251068 TI - Magnetic field actuated manipulation and transfer of oil droplets on a stable underwater superoleophobic surface. AB - The transport of fluids at functional interfaces, driven by the external stimuli, is well established. The lossless transport of oil-based fluids under water remains a challenge, however, due to their high stickiness towards the surface. Here, a superhydrophilic and underwater superoleophobic tri-phase water/oil/solid nanoarray surface has been designed and prepared. The unique tri-phase surface exhibits underwater superoleophobic properties with an extremely low stickiness towards oil-based fluids. The magnetic-field-driven manipulation and transport of oil-based magnetic fluids are demonstrated under water, which opens up a new pathway to design flexible and smart devices for the control and transfer of liquid droplets by using tri-phase systems. PMID- 27251069 TI - Multiple pregnancy is the leading contributor to cesarean sections in in vitro fertilization pregnancies: An analysis using the Robson 10-group classification system. AB - AIM: In vitro fertilization (IVF) pregnancy is an important contributor to rising cesarean section (CS) rates. The profile of CS in this group is not well documented. This study sought to identify leading patient categories of the Robson 10-Group Classification System (TGCS) contributing to the high IVF CS rate. METHODS: We carried out a prospective study of IVF patients who delivered in the Singapore General Hospital from January 2010 to July 2012. Parity, singleton/multiple pregnancy, previous CS, mode of labor onset and gestational age at delivery were collected based on the TGCS. All other deliveries during the study period served as control. RESULTS: There were a total of 215 IVF deliveries, of which 114 (54.4%) were CS. Group 8 (all multiple pregnancies) was the greatest contributor to the overall CS rate (43.0%). Group 2 (term nulliparous singleton cephalic pregnancies with induction of labor or planned CS) was the second largest contributor to overall CS rate (12.3%). The third and fourth leading contributors were Group 10 (preterm singleton pregnancies) and Group 5 (pregnancies with previous CS), respectively. In contrast, these two groups were top contributors to the overall CS rate for the control group. CONCLUSION: Multiple pregnancy is the principal contributor to CS in our IVF population, and reducing its incidence may reduce its CS rate. Among singleton pregnancies, planned CS and failed induction for cephalic term pregnancies and preterm singleton pregnancies were the next largest contributors, suggesting a higher prevalence of maternal request and high-risk obstetric indications requiring interventions at preterm gestations. PMID- 27251071 TI - Etiology of intracerebral hemorrhage (ICH): novel insights from Zebrafish embryos. AB - Intracerebral hemorrhage (ICH) is the most severe subtype of stroke. Treatment options are scarce and given the high morbidity and mortality, relatively ineffective. Since patients with ICH may have an unknown heritable component, the need to identify potential risk factors necessitates the use of animal models to elucidate the genetic underpinnings of neurovascular development and, thereby, identify candidate regulatory pathways that are likely to be disrupted in patients with ICH. Zebrafish (Danio rerio) exhibits the anatomical and physiological complexity of a closed circulatory system observed in all vertebrates (with arteries, veins and capillaries). Moreover, studies over the last decade, aided by the application of chemical mutagenesis screens, morpholino mediated knockdown approaches and tissue-specific transgenic markers, have paved the way for the identification of several genes and signaling pathways that regulate developmental neurovascular stabilization. We hypothesize that mutations in these genes or pharmacological perturbations of these gene-products may account, at least in part, for the etiology of some forms of spontaneous ICH in humans. PMID- 27251070 TI - Escherichia coli-based cell-free extract development for protein-based cancer therapeutic production. AB - Cell-free protein synthesis has been around for decades but it has never been close to becoming a robust tool for the production of biotherapeutic agents. In this review, we focus on how Escherichia coli-based cell-free protein synthesis can be modified in various ways to produce challenging, complex anticancer biotherapeutics. Here we report progress in extract preparation and its relation to cell-free cancer research. The future prospects of cell-free technology and its potential in various areas of cancer therapeutics production are also highlighted. PMID- 27251072 TI - Single-molecule, antibody-free fluorescent visualisation of replication tracts along barcoded DNA molecules. AB - DNA combing is a standard technique to map DNA replication at the single molecule level. Typically, replicating DNA is metabolically labelled with nucleoside or nucleotide analogs, purified, stretched on coverslips and treated with fluorescent antibodies to reveal tracts of newly synthesized DNA. Fibres containing a locus of interest can then be identified by fluorescent in situ hybridization (FISH) with DNA probes. These steps are complex and the throughput is low. Here, we describe a simpler, antibody-free method to reveal replication tracts and identify the locus of origin of combed DNA replication intermediates. DNA was replicated in Xenopus egg extracts in the presence of a fluorescent dUTP. Purified DNA was barcoded by nicking with Nt.BspQI, a site-specific nicking endonuclease (NE), followed by limited nick-translation in the presence of another fluorescent dUTP. DNA was then stained with YOYO-1, a fluorescent DNA intercalator, and combed. Direct epifluorescence revealed the DNA molecules, their replication tracts and their Nt.BspQI sites in three distinct colours. Replication intermediates could thus be aligned to a reference genome map. In addition, replicated DNA segments showed a stronger YOYO-1 fluorescence than unreplicated segments. The entire length, replication tracts, and NE sites of combed DNA molecules can be simultaneously visualized in three distinct colours by standard epifluorescence microscopy, with no need for antibody staining and/or FISH detection. Furthermore, replication bubbles can be detected by quantitative YOYO-1 staining, eliminating the need for metabolic labelling. These results provide a starting point for genome-wide, single-molecule mapping of DNA replication in any organism. PMID- 27251073 TI - Reprogramming of somatic cells and nuclei by Xenopus oocyte and egg extracts. AB - Differentiated somatic cells and nuclei can be reprogrammed to a pluripotent undifferentiated state in the cytoplasm of oocytes and eggs. The ability of the gamete cells to induce reprogramming is not species-specific, so the extracts prepared from the oocytes and eggs of the African clawed frog Xenopus laevis can reprogram somatic mammalian cells. Thus, Xenopus egg extract-mediated reprogramming may constitute an alternative or complement other experimental reprogramming approaches, such as nuclear transfer, cell fusion, and transcription factor transduction. Here, we discuss the major reprogramming events induced by the extracts in somatic nuclei and cells, including remodeling of nuclear structure, replacement of somatic proteins with their embryonic counterparts, epigenetic modification of DNA and histones, transcriptional reprogramming, and initiation of DNA replication. We also address the advantages and limitations of the extract-based reprogramming approach. PMID- 27251074 TI - In silico analysis of histone H3 gene expression during human brain development. AB - Precise regulation of chromatin structure is essential for proper development of higher eukaryotes, and methylation of histone H3 at lysine-27 (H3K27) by the Polycomb Repressive Complex 2 (PRC2) component EZH2 has emerged as an important and conserved mechanism to ensure silencing of developmentally regulated genes. Recurrent mutations within the histone H3 genes H3F3A and HIST1H3B that convert K27 to methionine (H3K27M) and disrupt the global H3K27 methylation landscape and PRC2-dependent silencing, have recently been identified in pediatric high-grade gliomas including Diffuse Intrinsic Pontine Glioma (DIPG) and Glioblastoma multiforme (GBM; Type IV glioma). These findings have generated renewed interest in the dynamics of histone genes and their expression, which have been difficult to study due to redundancy and high sequence homology within the H3 gene family. In this in silico study, we re-evaluated genomic organization of the human H3 gene family and expression of these genes in the human brain, utilizing public RNA-based sequence datasets for the human genome and brain development. We identified transcriptional activity from at least 17 protein-encoding H3 genes in the developing brain, comprising at least 14 canonical (H3.1)-like and 3 'replication-independent' (H3.3)-like forms, and encoding six distinct H3 isoforms. Transcripts for H3.3 genes including H3F3A show gradual decrease in abundance associated with developmental progression, whereas H3.1 transcripts including HIST1H3B tend to be strongly downregulated at an early prenatal stage and remain essentially silent thereafter. Twelve genes, including members of both H3.1 and H3.3 classes, contain a K27-AAG codon that is mutable to that for M (ATG), whereas the remaining contain the alternative, AAA codon for K at this position. H3F3A is the only H3.3-like gene containing the K27-AAG codon, whereas HIST1H3B is among ten H3.1-like genes containing this codon. This data indicates that, in the early developing human brain, HIST1H3B constitutes the largest proportion of H3.1 transcripts among H3.1 isoforms. We suggest that the apparent overrepresentation of K27M mutations in H3F3A relative to other H3 isoforms may result from its uniqueness among H3.3s for the K27-AAG codon and the functional relationship between H3.3 and PRC2, whereas overrepresentation of K27M mutations in HIST1H3B may be a product of strong relative expression of this gene in the early developing brain. PMID- 27251075 TI - Cell optoporation with a sub-15 fs and a 250-fs laser. AB - We employed two commercially available femtosecond lasers, a Ti:sapphire and a ytterbium-based oscillator, to directly compare from a user's practical point-of view in one common experimental setup the efficiencies of transient laser-induced cell membrane permeabilization, i.e., of so-called optoporation. The experimental setup consisted of a modified multiphoton laser-scanning microscope employing high-NA focusing optics. An automatic cell irradiation procedure was realized with custom-made software that identified cell positions and controlled relevant hardware components. The Ti:sapphire and ytterbium-based oscillators generated broadband sub-15-fs pulses around 800 nm and 250-fs pulses at 1044 nm, respectively. A higher optoporation rate and posttreatment viability were observed for the shorter fs pulses, confirming the importance of multiphoton effects for efficient optoporation. PMID- 27251076 TI - Noncontact speckle-based optical sensor for detection of glucose concentration using magneto-optic effect. AB - We experimentally verify a speckle-based technique for noncontact measurement of glucose concentration in the bloodstream. The final device is intended to be a single wristwatch-style device containing a laser, a camera, and an alternating current (ac) electromagnet generated by a solenoid. The experiments presented are performed in vitro as proof of the concept. When a glucose substance is inserted into a solenoid generating an ac magnetic field, it exhibits Faraday rotation, which affects the temporal changes of the secondary speckle pattern distributions. The temporal frequency resulting from the ac magnetic field was found to have a lock-in amplification role, which increased the observability of the relatively small magneto-optic effect. Experimental results to support the proposed concept are presented. PMID- 27251077 TI - Diffuse optical microscopy for quantification of depth-dependent epithelial backscattering in the cervix. AB - A fiber optic imaging approach is presented using structured illumination for quantification of almost pure epithelial backscattering. We employ multiple spatially modulated projection patterns and camera-based reflectance capture to image depth-dependent epithelial scattering. The potential diagnostic value of our approach is investigated on cervical ex vivo tissue specimens. Our study indicates a strong backscattering increase in the upper part of the cervical epithelium caused by dysplastic microstructural changes. Quantization of relative depth-dependent backscattering is confirmed as a potentially useful diagnostic feature for detection of precancerous lesions in cervical squamous epithelium. PMID- 27251079 TI - The reduction in circulating levels of melatonin may be associated with the development of preeclampsia. AB - Placental dysfunction and oxidative stress contribute to the pathogenesis of preeclampsia, which is a pregnancy-specific disorder. It has been suggested that the incidence of preeclampsia has a seasonal variation. Melatonin, as a seasonal factor, has been suggested to be involved in a successful pregnancy. In this study, we investigated the association of circulating levels of melatonin with preeclampsia. Serum was collected from women with preeclampsia (n=113) and gestation-matched healthy pregnant women, and the levels of melatonin were measured. In addition, the expression of melatonin receptors was examined in preeclamptic placentae (n=27). The association of the incidence of preeclampsia and seasonal variation was also analysed from 1491 women with preeclampsia within 77 745 healthy pregnancies. The serum levels of melatonin were significantly reduced in women with preeclampsia at presentation and these reduced serum levels of melatonin were not associated with the severity or time onset of preeclampsia nor with seasonal variation. The expression of melatonin receptor, MT1 was reduced in preeclamptic placentae. The incidence of preeclampsia was did exhibit seasonal variation, but this was largely due to the increase in the incidence of mild or late-onset preeclampsia. Our results demonstrate that reduced melatonin levels are associated with the development of preeclampsia but that the circulating levels of melatonin do not appear to be subject to seasonal variation during pregnancy. PMID- 27251078 TI - Incident hypertension and its prediction model in a prospective northern urban Han Chinese cohort study. AB - Trends in incidence and prevalence of hypertension are grave in China and identifying high-risk, non-hypertension individuals for intervention may delay hypertension onset. We aimed to investigate the incidence of hypertension in northern urban Han Chinese population and construct multivariable hypertension prediction models through the prospective cohort, which included 7537 men and 4960 women free of hypertension at baseline between 2005 and 2010. During 38 958 person-years of follow-up, 2785 participants (men, 72.57%; women, 27.43%) developed hypertension. The incidence density of hypertension was 71.48 per 1000 person-year. In multivariable backward cox analyses, age, body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose and current drinking were retained for both men and women, while gamma glutamyl transferase only for men, total cholesterol, neutrophil granulocyte and current smoking only for women. The area under receiver operating characteristic curve (AUC) was 0.761 (95% confidence interval (CI), 0.752-0.771) for men and 0.753 (95% CI, 0.741-0.765) for women, even after 10-fold cross-validation, the AUC was 0.760 (95% CI, 0.751-0.770) for men and 0.749 (95% CI, 0.737-0.761) for women. Through risk stratification, the absolute risk of incident hypertension in 5 years at moderate, high and very high risk level was 2.13, 3.84 and 6.14 times that of those who were at low risk in men, and 1.30, 2.56 and 6.01 times that of those who were at low risk in women. Our findings identified predictors of incident hypertension and indicated that the sex-specific multivariable prediction models would be simply used to estimate the risk of incident hypertension. PMID- 27251080 TI - Utility of blood pressure genetic risk score in admixed Hispanic samples. AB - Hypertension is strongly influenced by genetic factors. Although hypertension prevalence in some Hispanic sub-populations is greater than in non-Hispanic whites, genetic studies on hypertension have focused primarily on samples of European descent. A recent meta-analysis of 200 000 individuals of European descent identified 29 common genetic variants that influence blood pressure, and a genetic risk score derived from the 29 variants has been proposed. We sought to evaluate the utility of this genetic risk score in Hispanics. The sample set consists of 1994 Hispanics from 2 cohorts: the Northern Manhattan Study (primarily Dominican/Puerto Rican) and the Miami Cardiovascular Registry (primarily Cuban/South American). Risk scores for systolic and diastolic blood pressure were computed as a weighted sum of the risk alleles, with the regression coefficients reported in the European meta-analysis used as weights. Association of risk score with blood pressure was tested within each cohort, adjusting for age, age2, sex and body mass index. Results were combined using an inverse variance meta-analysis. The risk score was significantly associated with blood pressure in our combined sample (P=5.65 * 10-4 for systolic and P=1.65 * 10-3 for diastolic) but the magnitude of the effect sizes varied by degree of European, African and Native American admixture. Further studies among other Hispanic sub populations are needed to elucidate the role of these 29 variants and identify additional genetic and environmental factors contributing to blood pressure variability in Hispanics. PMID- 27251082 TI - Into the Looking Glass: Literacy Acquisition and Mirror Invariance in Preschool and First-Grade Children. AB - At what point in reading development does literacy impact object recognition and orientation processing? Is it specific to mirror images? To answer these questions, forty-six 5- to 7-year-old preschoolers and first graders performed two same-different tasks differing in the matching criterion-orientation-based versus shape-based (orientation independent)-on geometric shapes and letters. On orientation-based judgments, first graders outperformed preschoolers who had the strongest difficulty with mirrored pairs. On shape-based judgments, first graders were slower for mirrored than identical pairs, and even slower than preschoolers. This mirror cost emerged with letter knowledge. Only first graders presented worse shape-based judgments for mirrored and rotated pairs of reversible (e.g., b d; b-q) than nonreversible (e.g., e-?) letters, indicating readers' difficulty in ignoring orientation contrasts relevant to letters. PMID- 27251081 TI - A common polymorphism rs1800247 in osteocalcin gene is associated with hypertension and diastolic blood pressure levels: the Shanghai Changfeng study. AB - Osteocalcin may have a role in hypertension due to its close relationship with energy metabolism and insulin sensitivity. The aim of this study was to evaluate the association of a common polymorphism rs1800247 in osteocalcin gene with hypertension and related traits. This was a population-based cross-sectional study including 5647 individuals. Baseline information was collected. Body mass index (BMI), waist circumference, blood pressure, glucose and lipids were determined. Homeostasis model assessment for insulin resistance (HOMA-IR) was used to estimate insulin sensitivity. Genotyping was performed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. The carriers of C allele of rs1800247 were associated with a decreased odds of hypertension compared with the carriers of T allele adjusted for age, sex and BMI (odds ratio (OR)=0.89, 95% confidence interval (CI) 0.81-0.97, P=0.01). The carriers of C allele were also associated with a lower diastolic blood pressure (DBP) level adjusted for age, sex and BMI in normotensive individuals (beta=-0.55, 95% CI 0.99 to -0.10, P=0.02), but its association with systolic blood pressure levels was not significant. The interaction between rs1800247 and HOMA-IR on hypertension was significant (P<0.001). In the stratified analysis by the median of HOMA-IR (1.93), rs1800247 was significantly associated with hypertension in the subgroup with HOMA-IR?1.93 (OR=0.82, 95% CI 0.71-0.94, P=0.005), but this association was not significant in the subgroup with HOMA-IR >1.93. We demonstrated that a common polymorphism rs1800247 in osteocalcin gene was associated with hypertension and DBP levels. The association of rs1800247 with hypertension was affected by its interaction with HOMA-IR. PMID- 27251083 TI - Isolation of yeast candidates for efficient sophorolipids production: their production potentials associate to their lineage. AB - Eleven biosurfactant-producing strains were newly isolated from environmental samples using a drop-collapse assay and thin-layer chromatography (TLC). According to the TLC analysis, the separation patterns of the glycolipid spots of nine dominant strains corresponded to that of the sophorolipids produced by a Starmerella bombicola type strain. The retention factor values of the spot patterns of two strains were less than those of the others. Two representative major products were purified, and their molecular structures were determined. The major products were identified as diacetylated lactonic and acidic sophorolipids. The fatty acid moieties of both compounds were estimated to be 17-hydroxymethyl hexadecenoic acid. The amounts of glycolipids ranged from 5.0 to 22.9 g/L after 4 d of cultivation. According to a phylogenetic analysis, the strains were identified as Starmerella bombicola and Candida floricola. PMID- 27251085 TI - Adhere, Degrade, and Move: The Three-Step Model of Invasion. AB - Experimental work during the period 1975-1986 revealed the crucial importance of the extracellular matrix (ECM) in tumor cell invasion and metastasis, and culminated in the three-step hypothesis of invasion. The first step is tumor cell attachment to the ECM. The second step is proteolytic degradation of the ECM, led by advancing protruding actin-rich pseudopods. The third step is migration of the tumor cell body through the remodeled matrix. This mechanistic scheme is widely accepted and continues to generate insights related to the large number of molecules, inside and outside invading cells, which all play a role in each of the three steps. Understanding the interaction of the tumor cells with the ECM has never been more clinically important. The ECM is not just a passive mechanical scaffold. Instead, the ECM is an active participant in neoplastic and physiologic invasion, and acts as an information highway, an immune sanctuary, and a storage depot supporting tumor growth and drug resistance. Cancer Res; 76(11); 3115-7. (c)2016 AACRSee related article by Liotta, Cancer Res 1986;46:1 7Visit the Cancer Research 75(th) Anniversary timeline. PMID- 27251086 TI - Implications of Increase in Vascular Permeability in Tumors by VEGF: A Commentary on the Pioneering Work of Harold Dvorak. AB - See related article by Senger et al., Cancer Res 1986;46:5629-32Visit the Cancer Research 75(th) Anniversary timeline. PMID- 27251087 TI - Correction: Delivery of Therapeutics Targeting the mRNA-Binding Protein HuR Using 3DNA Nanocarriers Suppresses Ovarian Tumor Growth. PMID- 27251088 TI - It's a matter of respect. PMID- 27251089 TI - Epidemiology of dementia and its burden in the city of Kolkata, India. AB - OBJECTIVES: Increase in aging population is expected to lead to increasing prevalence of dementia in India. In this study, we aimed to determine prevalence, incidence, and mortality of dementia and its subtypes and assess dementia burden in terms of disability-adjusted life years (DALY). METHODS: A community study was conducted over 5 years (2003-2008) in Kolkata, India, on 100,802 (males 53,209) randomly selected subjects to assess prevalence and capture data on incident cases and deaths. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, based on Global Burden of Disease 2010 approach. RESULTS: During 2003-2004, there were 103 (men 55) cases of dementia. The prevalence was 1.53% (age adjusted 1.12%) at age >=65 years. In those >=55 years age, average annual incidence rate of dementia was 72.57 per 100,000. All-cause standardized mortality ratio in dementia cases was 4.74 (men 6.19, women 3.03). The burden of dementia in 2007-2008 revealed that overall YLL was 47.13 per 100,000 and YLD ranged from 1.87 to 16.95 per 100,000 depending on the clinical severity of dementia. The overall DALY lost per 100,000 due to dementia for the year 2007-2008 was 74.19. CONCLUSIONS: This community study revealed a low prevalence and incidence of dementia with consequent low DALY-derived burden of illness compared with many industrialized nations. YLL formed major component of DALY indicating premature mortality to be an outcome of dementia burden. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27251090 TI - Genetic modulators of sickle cell disease in French Guiana: Markers of the slave trade. AB - OBJECTIVES: Sickle cell disease (SCD) is the leading genetic disease in French Guiana, reflecting the predominantly African ancestry of the Guianese population. Our purpose was to characterize the genetic modulators of SCD in order to retrace the origin of the population in light of the slave trade. METHODS: We have studied the sickle cell genotype, the betaS haplotypes, the alpha and beta thalassemia and the UGT1A1 promoter polymorphisms in 224 Guianese patients with SCD. RESULTS: The genotypes of SCD were HbSS 65.6%, HbSC 24.5%, and HbS-beta thalassemia 9.4%. The most frequent betaS haplotypes were the Benin haplotype (65.9% of the chromosomes) and the Bantu (20.5%). Alpha thalassemic deletions were present in 37% of the patients and homozygosity for the (TA)7 allele of the UGT1A1 promoter in 21.4%. When the patients' origins were considered, 3 groups, Noir Marron, Haitians and Creoles, displayed distinctive characteristics. The HbSC genotype, the Benin haplotype, and the homozygous UGT1A1 genotype TA7/TA7 were significantly more frequent in Noir Marron. The Haitian patients were characterized by the occurrence of alpha-thalassemia and beta-thalassemia and by a higher prevalence of the Bantu haplotype. In the group of Creole patients, the genotype HbSS was predominant but the other modulators of SCD were associated with intermediate risk. CONCLUSIONS: The results highlight the genetic diversity of the Guianese population and are concordant with historical data on the slave trade showing a West African origin for Noir Marron and a Central African origin for Haitians, while Guianese Creoles are highly admixed. Am. J. Hum. Biol. 28:811 816, 2016. (c) 2016Wiley Periodicals, Inc. PMID- 27251091 TI - Expression of Cnnm1 and Its Association with Stemness, Cell Cycle, and Differentiation in Spermatogenic Cells in Mouse Testis. AB - Cyclin M1 (CNNM1) functions as a copper storage protein in neuronal cells. We report that Cnnm1 is expressed in mouse testis and brain and has a coding sequence of 1761 bp that encodes a 586 amino acid protein with a molecular weight of 66 kDa. Cnnm1 is expressed in the testes of mice from neonatal to adult stages with relatively higher levels in neonates. CNNM1 expression appeared to be restricted to c-KIT- and OCT3/4-positive cells in the testis, indicating that they are early spermatogonial cells. Spermatogonial stem cells in primary culture expressed Cnnm1, and their differentiation into embryoid body-like clusters in vitro resulted in the loss of Cnnm1 expression. Silencing of Cnnm1 in GC1-spg cells resulted in a significant reduction in the number of cells in G1 phase with concomitant increase in the numbers of cells in both S and G2/M phases. Further, retinoic acid downregulated the expression of Cnnm1 in GC1-spg cells. We conclude that CNNM1 is associated with stemness and self-renewal, and its downregulation triggers differentiation in spermatogonial cells in mouse. PMID- 27251092 TI - Matrix Metalloproteinase Expression in the Rat Myometrium During Pregnancy, Term Labor, and Postpartum. AB - Pregnancy, spontaneous term labor (TL), and postpartum (PP) involution are associated with changes in the cellular and extracellular matrix composition of the uterus. Both the uterine smooth muscle (myometrium) and the infiltrating peripheral blood leukocytes involved in the activation of labor secrete extracellular matrix-degrading enzymes (matrix metalloproteinases, MMPs) that can modulate cellular behavior and barrier function. MMP expression is induced by mechanical stretch in several tissues. We hypothesized that the expression and activity of myometrial MMPs and their tissue inhibitors (TIMPs) are modulated in preparation for TL and PP involution and are regulated by mechanical stretch of uterine walls imposed by the growing fetus. Myometrial tissues were collected from bilaterally and unilaterally pregnant rats across gestation, TL, and PP. Total RNA and proteins were subjected to real-time PCR and immunoblotting, respectively, and tissue localization and activity was examined by immunohistochemistry and in situ zymography. We found that Mmp7, Mmp11, and Mmp12 mRNA levels were upregulated during TL and PP, while Mmp2, Mmp3, Mmp8, Mmp9, Mmp10, and Mmp13 mRNAs were only upregulated during PP. Timp1-Timp4 were stably expressed throughout gestation with some fluctuations PP. Active MMP2 was induced in the empty uterine horn during gestation and in the gravid PP uterus, suggesting negative regulation by biological mechanical stretch. We conclude that specific subsets of uterine MMPs are differentially regulated in the rat myometrium in preparation for two major events: TL and PP uterine involution. PMID- 27251093 TI - N-Acetylcysteine Prevents Programmed Hypertension in Male Rat Offspring Born to Suramin-Treated Mothers. AB - Adulthood hypertension can be programmed by preeclampsia. Preeclampsia is associated with an imbalance in vasoactive factors, including nitric oxide (NO), hydrogen sulfide (H2S), and renin-angiotensin system (RAS). We examined whether maternal N-acetylcysteine (NAC) therapy prevented maternal suramin treatment induced programmed hypertension in offspring and explored the effects of this therapy on NO, H2S, and RAS pathways in the kidneys. Pregnant Sprague-Dawley rats were intraperitoneally administered 60 mg/kg suramin alone on Gestational Days 10 and 11 and were treated with or without 1% NAC through drinking water during the entire pregnancy and lactation period. Male offspring were divided into four groups (n = 8-10/group): control, suramin, NAC, and suramin plus NAC. All rat offspring were euthanized at 12 wk of age. Maternal suramin treatment induced programmed hypertension in male offspring, which was prevented by maternal NAC therapy. Suramin-induced programmed hypertension was associated with increased plasma asymmetric dimethylarginine (ADMA, an NO synthase inhibitor) level, decreased plasma l-arginine-to-ADMA ratio, and decreased renal dimethylarginine dimethylaminohydrolase (an ADMA-metabolizing enzyme) activity. Protective effects of NAC against suramin-induced programmed hypertension were associated with an increase in plasma glutathione level, increase in renal 3-mercaptopyruvate sulfurtransferase level, and restoration of suramin-induced reduction in H2S synthesis in the kidneys. Suramin treatment exerted negligible effect on the RAS pathway in the adult male offspring kidneys. Our data suggested interplay among suramin, ADMA-NO pathway, and H2S synthesis pathway in programmed hypertension. Furthermore, NAC administration in pregnant rats with hypertension prevented programmed hypertension in adult offspring. PMID- 27251094 TI - Conditions for Long-Term Culture of Cattle Undifferentiated Spermatogonia. AB - Continual and robust spermatogenesis relies on the actions of an undifferentiated spermatogonial population that contains stem cells. A remarkable feature of spermatogonial stem cells (SSCs) is the capacity to regenerate spermatogenesis following isolation from a donor testis and transplantation into a permissive recipient testis. This capacity has enormous potential as a tool for enhancing the reproductive capacity of livestock, which can improve production efficiency. Because SSCs are a rare subset of the undifferentiated spermatogonial population, a period of in vitro amplification in number following isolation from donor testicular tissue is essential. Here, we describe methodology for isolation of a cell fraction from prepubertal bull testes that is enriched for undifferentiated spermatogonia and long-term maintenance of the cells in both the feeder cell coculture and the feeder-free format. To achieve this method, we derived bovine fetal fibroblasts (BFF) to serve as feeders for optimizing medium conditions that promote maintenance of bovine undifferentiated spermatogonia for at least 2 mo. In addition, we devised a feeder-free system with BFF-conditioned medium that sustained bovine undifferentiated spermatogonia for at least 1 mo in vitro. The methodologies described could be optimized to provide platforms for exponential expansion of bovine SSCs that will provide the numbers needed for transplantation into recipient testes. PMID- 27251095 TI - Effects of glycerol, equilibration time and antioxidants on post-thaw functional integrity of bovine spermatozoa directly obtained from epididymis. AB - This work aimed to evaluate the effect of stabilisation times, glycerol concentration, and the catalase and superoxide dismutase supplementation of diluent on parameters of frozen-thawed spermatozoa from epididymis of Nelore bulls: Experiment 1: spermatozoa diluted in Tris-egg yolk with glycerol (3%, 5% or 7%) and stabilisation times (0, 2 or 4 hr at 5 degrees C); Experiment 2: Tris egg yolk only, Tris-egg yolk with catalase (CAT, 50 or 100 U ml-1 ) or superoxide dismutase (SOD, 50 or 100 U ml-1 ). Frozen-thawed spermatozoa were evaluated for kinetic parameters, plasma membrane and acrosome integrity, mitochondrial activity and IVF capacity. ALH and BCF were affected (p < .05) by glycerol at 3% after 4-hr equilibration time and 7% after 2-hr equilibration time. Glycerol 3% had lower (p < .05) iPM and iAc after 4 hr. Glycerol 5% had greater (p < .05) hPMM after 4 hr and iAc after 2 hr than at 0 hr. SOD 100 U ml-1 had lower (p < .05) linearity and wobble compared to control group. No was observed differences to fertilisation rate (p < .05) among groups. In conclusion, glycerol 5% in Tris egg yolk extender for 4 hr is suitable for the preservation of sperm kinetics and membrane integrity. CAT (50 and 100 U ml-1 ) or SOD (50-100 U ml-1 ) had no beneficial effects on sperm kinetics, plasma and acrosomal membrane integrity, mitochondrial activity or the capacity for IVF of frozen-thawed spermatozoa from epididymis of Nelore bulls. PMID- 27251096 TI - Detection of biofilm related genes, classical enterotoxin genes and agr typing among Staphylococcus aureus isolated from bovine with subclinical mastitis in southwest of Iran. AB - Staphylococcus aureus by producing biofilm and facilitating chronic infection is a common cause of mastitis in cows and thereby can cause food poisoning by production of enterotoxins in milk. The agr typing method is an important tool for epidemiological investigation about S. aureus. The aims of the present study were to detect biofilm related genes, 5 classical enterotoxin genes and the agr types among S. aureus isolates. The ability of S. aureus isolates to produce biofilm was evaluated by modified CRA plate. Six biofilm related adhesion genes (icaD, icaA, fnbA, bap, clfA and cna), five classical enterotoxin genes (sea, seb, sec, sed and see) and tst-1 gene were detected by PCR methods. Multiplex-PCR was used to determination of the agr groups. 55 out of 80(68.8%) S. aureus isolates were biofilm producer. The icaD gene was detected in 70 (87.5%) of isolates. The prevalence rates of fnbA, icaA, clfA, cna and bap were 72.5, 56.25, 50, 22.5, and 5% respectively. The agr group I and III were detected in 57.5% 25% of studied isolates. The sea, sed and tst-1 genes were found in 10%, 7.5% and 1.25% of isolates respectively. The majority of S. aureus were able to produce biofilm. Significant associations were observed between presence of the icaD, icaA, fnbA, clfA and the cna genes as well as biofilm formation. The present study revealed that isolates with the agr type III are more potent for biofilm production. Our data supported a possible link between the agr types and certain SE genes. PMID- 27251097 TI - Disseminated intravascular coagulation. PMID- 27251098 TI - Crystallographic Lattice Boltzmann Method. AB - Current approaches to Direct Numerical Simulation (DNS) are computationally quite expensive for most realistic scientific and engineering applications of Fluid Dynamics such as automobiles or atmospheric flows. The Lattice Boltzmann Method (LBM), with its simplified kinetic descriptions, has emerged as an important tool for simulating hydrodynamics. In a heterogeneous computing environment, it is often preferred due to its flexibility and better parallel scaling. However, direct simulation of realistic applications, without the use of turbulence models, remains a distant dream even with highly efficient methods such as LBM. In LBM, a fictitious lattice with suitable isotropy in the velocity space is considered to recover Navier-Stokes hydrodynamics in macroscopic limit. The same lattice is mapped onto a cartesian grid for spatial discretization of the kinetic equation. In this paper, we present an inverted argument of the LBM, by making spatial discretization as the central theme. We argue that the optimal spatial discretization for LBM is a Body Centered Cubic (BCC) arrangement of grid points. We illustrate an order-of-magnitude gain in efficiency for LBM and thus a significant progress towards feasibility of DNS for realistic flows. PMID- 27251099 TI - Stereochemical Recognition of Helicenes on Metal Surfaces. AB - The chiral recognition among biomolecules is fundamentally important for many processes of life, including the stereochemistry of evolution. Of special interest is chiral recognition during crystallization of racemates, when either homochiral recognition leads to a conglomerate of homochiral crystals or heterochiral recognition dominates resulting in a racemic compound. The complex nature of molecular recognition at the level of nucleation and crystal growth renders it difficult to understand and calls for manageable model systems. Notably, the approach of studying aggregation of molecules at surfaces under well defined conditions includes the benefit of the availability of a multitude of highly sensitive investigation methods, of which scanning tunneling microscopy (STM) with its submolecular resolution is tremendously valuable. Heterogeneous nucleation at surfaces is strongly favored over homogeneous nucleation in solution; hence, surfaces are significantly involved in stereochemical recognition during crystallization. Helicenes are a fascinating class of chiral compounds with outstanding optical activity. These pi-conjugated, ortho-fused, aromatic hydrocarbons are promising candidates for organic electronic devices such as sensors, circular dichroic photonics, liquid crystal displays or spin filters. But in particular the defined footprint of their terminal benzo rings on a surface makes them interesting for studying stereochemical recognition with different single crystalline surfaces and the impact this has, in turn, on intermolecular recognition. In this Account, we describe the self-assembly of helicenes on metal surfaces with the focus on stereochemical recognition in two dimensional structures. Using the isomeric all-carbon helicenes, heptahelicene and dibenzohelicene as examples, different aggregation phenomena on different surfaces of single crystalline copper, silver, and gold are investigated. By means of STM different modes of transmission of molecular handedness from single molecules into extended two-dimensional supramolecular structures are identified. For the problem of racemate versus conglomerate crystallization, the impact of surface and molecular structure and their interplay are analyzed. This leads to detailed conclusions about the importance of the match of molecular and surface binding sites for long-range self-assembly. The absence of polar groups puts emphasis on van der Waals interaction and their maximization by steric overlap of molecular parts in enantiomeric and diastereomeric interactions. With STM as a manipulation tool, dimers are manually separated in order to analyze their chiral composition. And finally, new nonlinear cooperative effects induced by small enantiospecific bias are discovered that lead to single enantiomorphism in two dimensional racemate crystals as well as in racemic multilayered films. By means of these model studies many details that govern chiral recognition at surfaces are rationalized. PMID- 27251100 TI - Catalytic Enantioselective Desymmetrization Reactions to All-Carbon Quaternary Stereocenters. AB - This Review summarizes the advances in the construction of all-carbon quaternary stereocenters via catalytic enantioselective desymmetrization of prochiral and meso-compounds, highlights the power and potential of this strategy in the total synthesis of natural products and biologically active compounds, and outlines the synthetic opportunities still available. PMID- 27251101 TI - The N-terminal zinc finger domain of Tgf2 transposase contributes to DNA binding and to transposition activity. AB - Active Hobo/Activator/Tam3 (hAT) transposable elements are rarely found in vertebrates. Previously, goldfish Tgf2 was found to be an autonomously active vertebrate transposon that is efficient at gene-transfer in teleost fish. However, little is known about Tgf2 functional domains required for transposition. To explore this, we first predicted in silico a zinc finger domain in the N-terminus of full length Tgf2 transposase (L-Tgf2TPase). Two truncated recombinant Tgf2 transposases with deletions in the N-terminal zinc finger domain, S1- and S2-Tgf2TPase, were expressed in bacteria from goldfish cDNAs. Both truncated Tgf2TPases lost their DNA-binding ability in vitro, specifically at the ends of Tgf2 transposon than native L-Tgf2TPase. Consequently, S1- and S2 Tgf2TPases mediated gene transfer in the zebrafish genome in vivo at a significantly (p < 0.01) lower efficiency (21%-25%), in comparison with L Tgf2TPase (56% efficiency). Compared to L-Tgf2TPase, truncated Tgf2TPases catalyzed imprecise excisions with partial deletion of TE ends and/or plasmid backbone insertion/deletion. The gene integration into the zebrafish genome mediated by truncated Tgf2TPases was imperfect, creating incomplete 8-bp target site duplications at the insertion sites. These results indicate that the zinc finger domain in Tgf2 transposase is involved in binding to Tgf2 terminal sequences, and loss of those domains has effects on TE transposition. PMID- 27251102 TI - High prevalence of unhealthy alcohol use and comparison of self-reported alcohol consumption to phosphatidylethanol among women engaged in sex work and their male clients in Cambodia. AB - BACKGROUND: In Cambodia, most of the female sex workers (FSW) work in venues where unhealthy alcohol use is ubiquitous and potentially contributing to the HIV epidemic. However, no accurate data exists. We compare self-reported unhealthy alcohol consumption to a biomarker of alcohol intake in Cambodian FSW and male clients, and determine factors associated with unhealthy alcohol use. METHODS: A cross-sectional study was conducted among FSW (n=100) and male clients (n=100) in entertainment and sex work venues in Cambodia. Self-reported unhealthy alcohol use (AUDIT-C) was compared to phosphatidylethanol (PEth) positive (>=50ng/ml), a biomarker of alcohol intake. Sociodemographics data was collected. Correlates of self-reported unhealthy alcohol use and PEth positive were determined. RESULTS: The prevalence of PEth positive in FSW was 60.0%. Self-reported unhealthy alcohol consumption was reported by 85.0% of the women. Almost all women (95.0%) testing PEth positive also reported unhealthy alcohol use. Prevalence of unhealthy alcohol consumption (self-report and PEth positive) was higher in FSW working in entertainment establishments compared to other sex work venues (p<0.01). Among male clients, 47.0% reported unhealthy alcohol consumption and 42.0% had a PEth positive. However, only 57.1% of male clients with PEth positive reported unhealthy alcohol use. CONCLUSIONS: Unhealthy alcohol consumption is prevalent in Cambodian sex work settings. Self-reported unhealthy alcohol use is well reported by FSW, but less by male clients. These findings highlight the urgency of using accurate measures of unhealthy alcohol consumption and integrating this health issue into HIV prevention interventions. PMID- 27251103 TI - Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine. AB - The long noncoding RNA Gomafu/MIAT/Rncr2 is thought to function in retinal cell specification, stem cell differentiation and the control of alternative splicing. To further investigate physiological functions of Gomafu, we created mouse knockout (KO) model that completely lacks the Gomafu gene. The KO mice did not exhibit any developmental deficits. However, behavioral tests revealed that the KO mice are hyperactive. This hyperactive behavior was enhanced when the KO mice were treated with the psychostimulant methamphetamine, which was associated with an increase in dopamine release in the nucleus accumbens. RNA sequencing analyses identified a small number of genes affected by the deficiency of Gomafu, a subset of which are known to have important neurobiological functions. These observations suggest that Gomafu modifies mouse behavior thorough a mild modulation of gene expression and/or alternative splicing of target genes. PMID- 27251105 TI - Controlled mechanical ventilation with constant positive end-expiratory pressure and alveolar recruitment manoeuvres during anaesthesia in laterally or dorsally recumbent horses. AB - OBJECTIVE: To compare the effects of controlled mechanical ventilation (CMV) and constant positive end-expiratory pressure (PEEP) and interposed recruitment manoeuvres (RMs) with those of CMV without PEEP on gas exchange during general anaesthesia and the early recovery period. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 48 Warmblood horses undergoing elective surgery in lateral (Lat) (n = 24) or dorsal (Dors) (n = 24) recumbency. METHODS: Premedication (romifidine), induction (diazepam and ketamine) and maintenance (isoflurane in oxygen) were identical in all horses. Groups Lat- CMV and Dors-CMV (each n = 12) were ventilated using CMV. Groups Lat-RM and Dors-RM (each n = 12) were ventilated using CMV with constant PEEP (10 cmH2O) and intermittent RMs (three consecutive breaths with peak inspiratory pressure of 60 cmH2O, 80 cmH2O and 60 cmH2O, respectively). RMs were applied as required to maintain PaO2 at > 400 mmHg (> 53.3 kPa). Dobutamine was given to maintain mean arterial blood pressure at > 60 mmHg. Physiological parameters were recorded every 10 minutes. Arterial blood gases were measured intra- and postoperatively. Statistical analyses were conducted using analyses of variance (anova),t tests and the Mann Whitney U-test. RESULTS: Horses in Dors-RM had higher PaO2 values [478 +/- 35 mmHg (63.7 +/- 4.6 kPa)] than horses in Dors-CMV [324 +/- 45 mmHg (43.2 +/- 6 kPa)] during anaesthesia and the early recovery period. There were no differences between horses in groups Lat-CMV and Lat-RM. Other measured parameters did not differ between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Ventilation with CMV, constant PEEP and interposed RM provided improved arterial oxygenation in horses in dorsal recumbency that lasted into the early recovery period, but had no benefit in horses in lateral recumbency. This mode of ventilation may provide a clinically practicable method of improving oxygenation in anaesthetized horses, especially in dorsal recumbency. PMID- 27251106 TI - Reduction of Laboratory Utilization in the Intensive Care Unit. AB - OBJECTIVE: In our academic intensive care unit (ICU), there is excess ordering of routine laboratory tests. This is partially due to a lack of transparency of laboratory-processing costs and to the admission order plans that favor daily laboratory test orders. We hypothesized that a program that involves physician and staff education and alters the current ICU order sets will lead to a sustained decrease in routine laboratory test ordering. DESIGN: Prospective cohort study. SETTING: Academic closed medical ICU (MICU). PATIENTS: All patients admitted to the MICU. METHODS: We consistently educated residents, faculty, and staff about laboratory test costs. We removed the daily laboratory test option from the admission order sets and asked residents to order needed laboratory test results every day. We only allowed the G3+I-STAT (arterial blood gas only) cartridges in the MICU in hopes of decreasing duplicative laboratory test results. We added laboratory review to the daily rounding checklist. MEASUREMENT AND MAIN RESULTS: Total number of laboratory tests per patient-day decreased from 39.43 to an average of 26.74 ( P <.001) over a 9-month period. The number of iSTAT laboratory tests per patient-day decreased from 7.37 to an average of 1.16 ( P < .001) over the same time period. The number of iSTAT/central laboratory processing duplicative laboratory tests per patient-day decreased from 0.17 to an average of 0.01 ( P < .001). The percentage of patients who have daily laboratory test orders decreased from 100% to an average of 11.94% ( P <. 001). US$123 436 in direct savings and US$258 035 dollars in indirect savings could be achieved with these trends. Intensive care unit morbidity and mortality were not impacted. CONCLUSION: A simple technique of resident, nursing, and ancillary staff education, combined with alterations in order sets using electronic medical records, can lead to a sustained reduction in laboratory test utilization over time and to significant cost savings without affecting patient safety. PMID- 27251107 TI - Elevated Red Cell Distribution Width Is Associated With Decreased Ventilator-Free Days in Critically Ill Patients. AB - INTRODUCTION: Elevated red cell distribution width (RDW) is associated with mortality in a variety of respiratory conditions. Recent data also suggest that RDW is associated with mortality in intensive care unit (ICU) patients. Although respiratory failure is common in the ICU, the relationship between RDW and pulmonary outcomes in the ICU has not been previously explored. Therefore, our goal was to investigate the association of admission RDW with 30-day ventilator free days (VFDs) in ICU patients. METHODS: We performed a retrospective analysis from an ongoing prospective, observational study. Patients were recruited from medical and surgical ICUs of a large teaching hospital in Boston, Massachusetts. The RDW was assessed within 1 hour of ICU admission. Poisson regression analysis was used to investigate the association of RDW (normal: 11.5%-14.5% vs elevated: >14.5%) with 30-day VFD, while controlling for age, sex, race, body mass index, Nutrition Risk in the Critically Ill score, the presence of chronic lung disease, Pao2/Fio2 ratio, and admission levels of hemoglobin, mean corpuscular volume, phosphate, albumin, C-reactive protein, and creatinine. RESULTS: A total of 637 patients comprised the analytic cohort. Mean RDW was 15 (standard deviation 4%), with 53% of patients in the normal range and 47% with elevated levels. Median VFD was 16 (interquartile range: 6-25) days. Poisson regression analysis demonstrated that ICU patients with elevated admission RDW were likely to have 32% lower 30 day VFDs compared to their counterparts with RDW in the normal range (incidence rate ratio: 0.68; 95% confidence interval: 0.55-0.83: P < .001). CONCLUSIONS: We observed an inverse association of RDW and 30-day VFD, despite controlling for demographics, nutritional factors, and severity of illness. This supports the need for future studies to validate our findings, understand the physiologic processes that lead to elevated RDW in patients with respiratory failure, and determine whether changes in RDW may be used to support clinical decision-making. PMID- 27251104 TI - Apoptosis-mediated endothelial toxicity but not direct calcification or functional changes in anti-calcification proteins defines pathogenic effects of calcium phosphate bions. AB - Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease. PMID- 27251109 TI - Effects of the large distribution of CdS quantum dot sizes on the charge transfer interactions into TiO2 nanotubes for photocatalytic hydrogen generation. AB - Hydrogen fuels generated by water splitting using a photocatalyst and solar irradiation are currently gaining the strength to diversify the world energy matrix in a green way. CdS quantum dots have revealed a hydrogen generation improvement when added to TiO2 materials under visible-light irradiation. In the present paper, we investigated the performance of TiO2 nanotubes coupled with CdS quantum dots, by a molecular bifunctional linker, on photocatalytic hydrogen generation. TiO2 nanotubes were obtained by anodization of Ti foil, followed by annealing to crystallize the nanotubes into the anatase phase. Afterwards, the samples were sensitized with CdS quantum dots via an in situ hydrothermal route using 3-mercaptopropionic acid as the capping agent. This sensitization technique permits high loading and uniform distribution of CdS quantum dots onto TiO2 nanotubes. The XPS depth profile showed that CdS concentration remains almost unchanged (homogeneous), while the concentration relative to the sulfate anion decreases by more than 80% with respect to the initial value after ~100 nm in depth. The presence of sulfate anions is due to the oxidation of sulfide and occurs in greater proportion in the material surface. This protection for air oxidation inside the nanotubular matrix seemingly protected the CdS for photocorrosion in sacrificial solution leading to good stability properties proved by long duration, stable photocurrent measurements. The effect of the size and the distribution of sizes of CdS quantum dots attached to TiO2 nanotubes on the photocatalytic hydrogen generation were investigated. The experimental results showed three different behaviors when the reaction time of CdS synthesis was increased in the sensitized samples, i.e. similar, deactivation and activation effects on the hydrogen production with regard to TiO2 nanotubes. The deactivation effect was related to two populations of sizes of CdS, where the population with a shorter band gap acts as a trap for the electrons photogenerated by the population with a larger band gap. Electron transfer from CdS quantum dots to TiO2 semiconductor nanotubes was proven by the results of UPS measurements combined with optical band gap measurements. This property facilitates an improvement of the visible-light hydrogen evolution rate from zero, for TiO2 nanotubes, to approximately 0.3 MUmol cm(-2) h(-1) for TiO2 nanotubes sensitized with CdS quantum dots. PMID- 27251108 TI - Vitamin D Status After Cardiopulmonary Bypass in Children With Congenital Heart Disease. AB - Deficiency in 25-hydroxyvitamin D (25OHD) is associated with increased morbidity and mortality in the critically ill. Children who underwent surgery for congenital heart disease under cardiopulmonary bypass (CPB) are typically deficient in 25OHD. It is unclear whether this deficiency is due to CPB. We hypothesized that CPB reduces the levels of 25OHD in children with congenital heart disease. We conducted a prospective observational study on children aged 2 months to 17 years who underwent CPB. Serum was collected at 3 time points: immediately before, immediately after surgery, and 24 hours after surgery. 25 Hydroxyvitamin D, 1,25-dihydroxyvitamin D, 1,25(OH)2D, vitamin D binding protein, and albumin levels were measured. Levels were compared using repeated measures analysis of variance. We enrolled 20 patients, 40% were deficient in 25OHD with levels <20 ng/mL prior to surgery. Mean (+/-standard deviation) of 25OHD at the 3 time points was 21.3 +/- 8 ng/mL, 19 +/- 5.8 ng/mL, and 19.5 +/- 6.6 ng/mL, respectively ( P = .02). The decrease in 25OHD was observed primarily in children with sufficient levels of 25OHD, with mean levels at the 3 time points: 26.8 +/- 4.2 ng/mL, 21.5 +/- 5.7 ng/mL, and 23.0 +/- 4.9 ng/mL, respectively ( P < .001). Calculated means of free fraction of 25OHD at the 3 time points were 6.2 +/- 2.8 pg/mL, 5.8 +/- 2.2 pg/mL, and 5.5 +/- 2.4 pg/mL, respectively, ( P = .04). Mean levels of 1,25(OH)2D were 63.7 +/- 34.9 ng/mL, 53.2 +/- 30.6 ng/mL, and 67.7 +/- 23.5 ng/mL ( P = .04). Vitamin D binding protein and albumin levels did not significantly change. Cardiopulmonary bypass decreases 25OHD by reducing the free fraction. Current investigations are geared to establish whether vitamin D deficiency is associated with outcomes and if treatment is appropriate. PMID- 27251110 TI - Effects of Information Visualization on Older Adults' Decision-Making Performance in a Medicare Plan Selection Task: A Comparative Usability Study. AB - BACKGROUND: Technology gains have improved tools for evaluating complex tasks by providing environmental supports (ES) that increase ease of use and improve performance outcomes through the use of information visualizations (info-vis). Complex info-vis emphasize the need to understand individual differences in abilities of target users, the key cognitive abilities needed to execute a decision task, and the graphical elements that can serve as the most effective ES. Older adults may be one such target user group that would benefit from increased ES to mitigate specific declines in cognitive abilities. For example, choosing a prescription drug plan is a necessary and complex task that can impact quality of life if the wrong choice is made. The decision to enroll in one plan over another can involve comparing over 15 plans across many categories. Within this context, the large amount of complex information and reduced working memory capacity puts older adults' decision making at a disadvantage. An intentionally designed ES, such as an info-vis that reduces working memory demand, may assist older adults in making the most effective decision among many options. OBJECTIVE: The objective of this study is to examine whether the use of an info-vis can lower working memory demands and positively affect complex decision-making performance of older adults in the context of choosing a Medicare prescription drug plan. METHODS: Participants performed a computerized decision-making task in the context of finding the best health care plan. Data included quantitative decision-making performance indicators and surveys examining previous history with purchasing insurance. Participants used a colored info-vis ES or a table (no ES) to perform the decision task. Task difficulty was manipulated by increasing the number of selection criteria used to make an accurate decision. A repeated measures analysis was performed to examine differences between the two table designs. RESULTS: Twenty-three older adults between the ages of 66 and 80 completed the study. There was a main effect for accuracy such that older adults made more accurate decisions in the color info-vis condition than the table condition. In the low difficulty condition, participants were more successful at choosing the correct answer when the question was about the gap coverage attribute in the info-vis condition. Participants also made significantly faster decisions in the info-vis condition than in the table condition. CONCLUSIONS: Reducing the working memory demand of the task through the use of an ES can improve decision accuracy, especially when selection criteria is only focused on a single attribute of the insurance plan. PMID- 27251111 TI - Cobalt oxyhydroxide nanoflake based fluorescence sensing platform for label-free detection of DNA. AB - Detection of specific DNA sequences is critical in life science. In this study, we investigated the interaction of cobalt oxyhydroxide (CoOOH) nanoflakes with DNA and their fluorescence quenching mechanism of a FAM-labeled single-stranded DNA (ssDNA) probe. ssDNA could adsorb on the CoOOH surface via electrostatic interactions and therefore the fluorescence of FAM was quenched. However, upon addition of targets, ssDNA was hybridized with target DNA and the formed double stranded DNA (dsDNA) had much weaker affinity to CoOOH, resulting in the retaining of fluorescence. Based on the affinity difference of CoOOH nanoflakes to ssDNA and dsDNA and fluorescence resonance energy transfer based fluorescence quenching, a mix-and-detect method was proposed for homogeneous detection of DNA. The proposed method is simple and can be finished in a few minutes with high sensitivity. Furthermore, it displays a wide linear range from 1 to 50 nM with a detection limit of 0.5 nM and is capable of detecting DNA in real biological samples. PMID- 27251112 TI - Concise Review: One Stone for Multiple Birds: Generating Universally Compatible Human Embryonic Stem Cells. AB - With ongoing clinical trials, human embryonic stem cells (hESCs) have shown substantial potential for regenerative medicine. However, due to the mismatch of human leukocyte antigens (HLAs) between hESC-derived allografts and recipients, immunosuppressant regimens must be used to prevent immune rejection of the grafts. Considerable efforts have been devoted to overcoming this hurdle via the derivation and banking of human nuclear transfer ESCs, parthenogenetic ESCs, and induced pluripotent stem cells. However, ethical and safety concerns remain, hindering the application of these types of pluripotent cells. Other approaches have recently been explored to generate universally compatible hESCs through the silencing or deletion of HLAs or genes essential for HLA expression, including beta-2-microglobulin and class-II MHC transactivator, as well as the induction of immunosuppression via the ectopic expression of non-classical HLAs (e.g., HLA-E and -G), cytotoxic T lymphocyte antigen 4 fused with immunoglobulin, and programmed death ligand-1. In this review, we introduce developments in this line of research and discuss strategies to reduce the tumorigenic concerns regarding hESCs, especially after they acquire the capability to escape immune surveillance. Stem Cells 2016;34:2269-2275. PMID- 27251114 TI - Cooperation Survives and Cheating Pays in a Dynamic Network Structure with Unreliable Reputation. AB - In a networked society like ours, reputation is an indispensable tool to guide decisions about social or economic interactions with individuals otherwise unknown. Usually, information about prospective counterparts is incomplete, often being limited to an average success rate. Uncertainty on reputation is further increased by fraud, which is increasingly becoming a cause of concern. To address these issues, we have designed an experiment based on the Prisoner's Dilemma as a model for social interactions. Participants could spend money to have their observable cooperativeness increased. We find that the aggregate cooperation level is practically unchanged, i.e., global behavior does not seem to be affected by unreliable reputations. However, at the individual level we find two distinct types of behavior, one of reliable subjects and one of cheaters, where the latter artificially fake their reputation in almost every interaction. Cheaters end up being better off than honest individuals, who not only keep their true reputation but are also more cooperative. In practice, this results in honest subjects paying the costs of fraud as cheaters earn the same as in a truthful environment. These findings point to the importance of ensuring the truthfulness of reputation for a more equitable and fair society. PMID- 27251115 TI - Metal organic frameworks mimicking natural enzymes: a structural and functional analogy. AB - In this review, we have portrayed the structure, synthesis and applications of a variety of biomimetic MOFs from an unprecedented angle. Synthetic MOF analogues of five distinct enzymes: phosphotriesterase, hydrogenase, cytochrome P450, chymotrypsin and carbonic anhydrase, have been discussed with their skeletal comparison to actual enzymatic active sites as reference, and an explanation of catalytic pathways from the mechanistic cycle of the corresponding enzymes is depicted. We demonstrated critically each of the five discrete situations by assimilating available benchmark researches in an attempt to provide a concise literature source on the ingenious design strategies and versatile biomimetic applications of this domain of materials. PMID- 27251116 TI - Hydrogen-bonded oligothiophene rosettes with a benzodithiophene terminal unit: self-assembly and application to bulk heterojunction solar cells. AB - Benzodithiophene-functionalized oligothiophene with barbituric acid hydrogen bonding unit self-assembles into nanoscopic structures via the formation of rosettes. The nanostructures show a power conversion efficiency of 3% upon mixing with PC61BM in bulk-heterojunction solar cells without thermal annealing. PMID- 27251118 TI - Troubled families and individualised solutions: an institutional discourse analysis of alcohol and drug treatment practices involving affected others. AB - Research shows that members of the families with patients suffering from alcohol and other drug-related issues (AOD) experience stress and strain. An important question is, what options do AOD treatment have for them when it comes to support? To answer this, we interviewed directors and clinicians from three AOD treatment institutions in Norway. The study revealed that family-oriented practices are gaining ground as a 'going concern'. However, the relative position of family-orientation in the services, is constrained and shaped by three other going concerns related to: (i) discourse on health and illness, emphasising that addiction is an individual medical and psychological phenomenon, rather than a relational one; (ii) discourse on rights and involvement, emphasising the autonomy of the individual patient and their right to define the format of their own treatment; and (iii) discourse on management, emphasising the relationship between cost and benefit, where family-oriented practices are defined as not being cost-effective. All three discourses are connected to underpin the weight placed on individualised practices. Thus, the findings point to a paradox: there is a growing focus on the needs of children and affected family members, while the possibility of performing integrated work on families is limited. PMID- 27251117 TI - Active diffusion and microtubule-based transport oppose myosin forces to position organelles in cells. AB - Even distribution of peroxisomes (POs) and lipid droplets (LDs) is critical to their role in lipid and reactive oxygen species homeostasis. How even distribution is achieved remains elusive, but diffusive motion and directed motility may play a role. Here we show that in the fungus Ustilago maydis ~95% of POs and LDs undergo diffusive motions. These movements require ATP and involve bidirectional early endosome motility, indicating that microtubule-associated membrane trafficking enhances diffusion of organelles. When early endosome transport is abolished, POs and LDs drift slowly towards the growing cell end. This pole-ward drift is facilitated by anterograde delivery of secretory cargo to the cell tip by myosin-5. Modelling reveals that microtubule-based directed transport and active diffusion support distribution, mobility and mixing of POs. In mammalian COS-7 cells, microtubules and F-actin also counteract each other to distribute POs. This highlights the importance of opposing cytoskeletal forces in organelle positioning in eukaryotes. PMID- 27251119 TI - Catecholamines and Paroxysmal Sympathetic Hyperactivity after Traumatic Brain Injury. AB - Paroxysmal sympathetic hyperactivity (PSH) affects a significant minority of people in the intensive care unit after severe traumatic brain injury. Systematic research has yet to elucidate or quantify the extent of the role of the catecholamines or adrenocortical and thyroid axis hormonal influences in the condition. Data were prospectively collected on 80 consecutive patients, 18 of whom developed clinical signs of PSH (22.5%). Catecholamine and hormonal data were collected sequentially at 4-h intervals or during and between episodes of PSH. Evaluated variables showed 200-300% increases in catecholamines and, to a lesser extent, adrenocortical hormones during paroxysms. The majority of PSH episodes (72%) were noted to be in response to an observable triggering event. These changes were not observed in subjects without PSH. These data go some way to explain why PSH produces adverse consequences in survivors of TBI with the condition. PMID- 27251121 TI - Double Tracheoesophageal Fistula and Azygos Lobe. PMID- 27251120 TI - Synthesis and evaluation of new 2-aminothiophenes against Mycobacterium tuberculosis. AB - Tuberculosis (TB) and its drug resistant forms kills more people than any other infectious disease. This fact emphasizes the need to identify new drugs to treat TB. 2-Aminothiophenes (2AT) have been reported to inhibit Pks13, a validated anti TB drug target. We synthesized a library of 42 2AT compounds. Among these, compound 33 showed remarkable potency against Mycobacterium tuberculosis (Mtb) H37RV (MIC = 0.23 MUM) and showed an impressive potency (MIC = 0.20-0.44 MUM) against Mtb strains resistant to isoniazid, rifampicin and fluoroquinolones. The site of action for the compound 33 is presumed to be Pks13 or an earlier enzyme in the mycolic acid biosynthetic pathway. This inference is based on structural similarity of the compound 33 with known Pks13 inhibitors, which is corroborated by mycolic acid biosynthesis studies showing that the compound strongly inhibits the biosynthesis of all forms of mycolic acid in Mtb. In summary, these studies suggest 33 represents a promising anti-TB lead that exhibits activity well below toxicity to human monocytic cells. PMID- 27251122 TI - Partial genotyping at polymorphic markers can improve heritability estimates in sibling groups. AB - Accurate estimates of heritability (h2) are necessary to assess adaptive responses of populations and evolution of fitness-related traits in changing environments. For plants, h2 estimates generally rely on maternal progeny designs, assuming that offspring are either half-sibs or unrelated. However, plant mating systems often depart from half-sib assumptions, this can bias h2 estimates. Here, we investigate how to accurately estimate h2 in nonmodel species through the analysis of sibling designs with a moderate genotyping effort. We performed simulations to investigate how microsatellite marker information available for only a subset of offspring can improve h2 estimates based on maternal progeny designs in the presence of nonrandom mating, inbreeding in the parental population or maternal effects. We compared the basic family method, considering or not adjustments based on average relatedness coefficients, and methods based on the animal model. The animal model was used with average relatedness information, or with hybrid relatedness information: associating one generation pedigree and family assumptions, or associating one-generation pedigree and average relatedness coefficients. Our results highlighted that methods using marker-based relatedness coefficients performed as well as pedigree based methods in the presence of nonrandom mating (i.e. unequal male reproductive contributions, selfing), offering promising prospects to investigate in situ heritabilities in natural populations. In the presence of maternal effects, only the use of pairwise relatednesses through pedigree information improved the accuracy of h2 estimates. In that case, the amount of father-related offspring in the sibling design is the most critical. Overall, we showed that the method using both one-generation pedigree and average relatedness coefficients was the most robust to various ecological scenarios. PMID- 27251124 TI - Increase of anthraquinone content in Rubia cordifolia cells transformed by native and constitutively active forms of the AtCPK1 gene. AB - KEY MESSAGE: Overexpression of both native and mutant forms of AtCPK1 in Rubia cordifolia cells increased anthraquinone production and transcript abundance of the RcIPPI, RcOSBL, RcOSBS , and RcICS genes to different extents. Calcium dependent protein kinases (CDPKs) are involved in various cell processes and are regulated by a calcium signal system. CDPKs also function in plant defense against stress factors such as pathogens, temperature, and salinity. In this study, we compared the effect of heterologous expression of two forms of the Arabidopsis AtCPK1 gene, native and constitutively active (Ca(2+)-independent), on anthraquinone production in transgenic Rubia cordifolia cells. Significant qualitative and quantitative differences were found in the content of anthraquinone derivatives in control and AtCPK1-transgenic calli. Expression of the AtCPK1 gene increased anthraquinone production by 3 and 12 times for native and constitutively active forms, respectively, compared with control cells. In addition, we identified and quantified the expression of genes encoding key enzymes of the anthraquinone biosynthesis pathway, including isochorismate synthase (ICS), o-succinylbenzoate synthase (OSBS), o-succinylbenzoate ligase (OSBL), and isopentenyl diphosphate isomerase (IPPi). In all AtCPK1-transgenic cell lines, expression of ICS, OSBS, OSBL, and IPPi increased considerably at 14 15 days of subculture and decreased at the end of cultivation (30 days). The results suggest that both native and constitutively active AtCPK1 forms induced anthraquinone accumulation at the logarithmic growth stage via enhancement of expression of genes involved in the metabolism of anthraquinones or their regulatory mechanisms. PMID- 27251123 TI - Unity and diversity of executive functions: Individual differences as a window on cognitive structure. AB - Executive functions (EFs) are high-level cognitive processes, often associated with the frontal lobes, that control lower level processes in the service of goal directed behavior. They include abilities such as response inhibition, interference control, working memory updating, and set shifting. EFs show a general pattern of shared but distinct functions, a pattern described as "unity and diversity". We review studies of EF unity and diversity at the behavioral and genetic levels, focusing on studies of normal individual differences and what they reveal about the functional organization of these cognitive abilities. In particular, we review evidence that across multiple ages and populations, commonly studied EFs (a) are robustly correlated but separable when measured with latent variables; (b) are not the same as general intelligence or g; (c) are highly heritable at the latent level and seemingly also highly polygenic; and (d) activate both common and specific neural areas and can be linked to individual differences in neural activation, volume, and connectivity. We highlight how considering individual differences at the behavioral and neural levels can add considerable insight to the investigation of the functional organization of the brain, and conclude with some key points about individual differences to consider when interpreting neuropsychological patterns of dissociation. PMID- 27251126 TI - Impact of Low Procalcitonin Results on Antibiotic Administration in Hospitalized Patients at a Tertiary Care Center. AB - Procalcitonin is a sensitive and specific marker of bacterial infection; low results allow clinicians to safely de-escalate antibiotics. This retrospective cohort study aimed to determine the effect of low procalcitonin results on withholding, discontinuing, or de-escalating antibiotics in hospitalized patients at a tertiary care center. Antibiotics were initiated or continued without de escalation in 55% of patients with low procalcitonin results. Among patients with low procalcitonin results, the primary service, but not measures of patient complexity, disease severity, or underlying disease process (lower respiratory tract infection evaluation versus systemic inflammatory response syndrome/possible sepsis) was associated with initiation or continued broad spectrum antibiotic use. Provider-level factors may be an important variable in the initiation or continued use of broad-spectrum antibiotics for patients with low procalcitonin levels. PMID- 27251125 TI - A sunflower WRKY transcription factor stimulates the mobilization of seed-stored reserves during germination and post-germination growth. AB - KEY MESSAGE: The sunflower transcription factor HaWRKY10 stimulates reserves mobilization in Arabidopsis. Gene expression and enzymes activity assays indicated that lipolysis and gluconeogenesis were increased. Microarray results suggested a parallelism in sunflower. Germinating oilseeds converts stored lipids into sugars, and thereafter in metabolic energy that is used in seedling growth and establishment. During germination, the induced lipolysis linked to the glyoxylate pathway and gluconeogenesis produces sucrose, which is then transported to the embryo and driven through catabolic routes. Herein, we report that the sunflower transcription factor HaWRKY10 regulates carbon partitioning by reducing carbohydrate catabolism and increasing lipolysis and gluconeogenesis. HaWRKY10 was regulated by abscisic acid and gibberellins in the embryo leaves 48 h after seed imbibition and highly expressed during sunflower seed germination and seedling growth, concomitantly with lipid mobilization. Sunflower leaf disks overexpressing HaWRKY10 showed repressed expression of genes related to sucrose cleavage and glycolysis compared with controls. Moreover, HaWRKY10 constitutive expression in Arabidopsis seeds produced higher decrease in lipid reserves, whereas starch and sucrose were more preserved compared with wild type. Gene transcripts abundance and enzyme activities involved in stored lipid mobilization and gluconeogenesis increased more in transgenic than in wild type seeds 36 h after imbibition, whereas the negative regulator of lipid mobilization, ABI4, was repressed. Altogether, the results point out a functional parallelism between tissues and plant species, and reveal HaWRKY10 as a positive regulator of storage reserve mobilization in sunflower. PMID- 27251127 TI - Is a Picture Worth a Thousand Words? Few Evidence-Based Features of Dietary Interventions Included in Photo Diet Tracking Mobile Apps for Weight Loss. AB - BACKGROUND: Apps using digital photos to track dietary intake and provide feedback are common, but currently there has been no research examining what evidence-based strategies are included in these apps. METHODS: A content analysis of mobile apps for photo diet tracking was conducted, including whether effective techniques for interventions promoting behavior change, including self regulation, for healthy eating (HE) are targeted. An initial search of app stores yielded 34 apps (n = 8 Android and Apple; n = 11 Android; n = 15 Apple). One app was removed (unable to download), and other apps (n = 4) were unable to be rated (no longer available). Remaining apps (n = 29) were downloaded, reviewed, and coded by 2 independent reviewers to determine the number of known effective self regulation and other behavior change techniques included. The raters met to compare their coding of the apps, calculate interrater agreement, resolve any discrepancies, and come to a consensus. RESULTS: Six apps (21%) did not utilize any of the behavior change techniques examined. Three apps (10%) provided feedback to users via crowdsourcing or collective feedback from other users and professionals, 7 apps (24%) used crowdsourcing or collective feedback, 1 app (3%) used professionals, and 18 apps (62%) did not provide any dietary feedback to users. CONCLUSION: Few photo diet-tracking apps include evidence-based strategies to improve dietary intake. Use of photos to self-monitor dietary intake and receive feedback has the potential to reduce user burden for self-monitoring, yet photo diet tracking apps need to incorporate known effective behavior strategies for HE, including self-regulation. PMID- 27251128 TI - Severe anaemia associated with Plasmodium falciparum infection in children: consequences for additional blood sampling for research. AB - BACKGROUND: Plasmodium falciparum infection may cause severe anaemia, particularly in children. When planning a diagnostic study on children suspected of severe malaria in sub-Saharan Africa, it was questioned how much blood could be safely sampled; intended blood volumes (blood cultures and EDTA blood) were 6 mL (children aged <6 years) and 10 mL (6-12 years). A previous review [Bull World Health Organ. 89: 46-53. 2011] recommended not to exceed 3.8 % of total blood volume (TBV). In a simulation exercise using data of children previously enrolled in a study about severe malaria and bacteraemia in Burkina Faso, the impact of this 3.8 % safety guideline was evaluated. METHODS: For a total of 666 children aged >2 months to <12 years, data of age, weight and haemoglobin value (Hb) were available. For each child, the estimated TBV (TBVe) (mL) was calculated by multiplying the body weight (kg) by the factor 80 (ml/kg). Next, TBVe was corrected for the degree of anaemia to obtain the functional TBV (TBVf). The correction factor consisted of the rate 'Hb of the child divided by the reference Hb'; both the lowest ('best case') and highest ('worst case') reference Hb values were used. Next, the exact volume that a 3.8 % proportion of this TBVf would present was calculated and this volume was compared to the blood volumes that were intended to be sampled. RESULTS: When applied to the Burkina Faso cohort, the simulation exercise pointed out that in 5.3 % (best case) and 11.4 % (worst case) of children the blood volume intended to be sampled would exceed the volume as defined by the 3.8 % safety guideline. Highest proportions would be in the age groups 2-6 months (19.0 %; worst scenario) and 6 months-2 years (15.7 %; worst case scenario). A positive rapid diagnostic test for P. falciparum was associated with an increased risk of violating the safety guideline in the worst case scenario (p = 0.016). CONCLUSIONS: Blood sampling in children for research in P. falciparum endemic settings may easily violate the proposed safety guideline when applied to TBVf. Ethical committees and researchers should be wary of this and take appropriate precautions. PMID- 27251129 TI - Differential effects of the pharmacological stressor yohimbine on impulsive decision making and response inhibition. AB - RATIONALE: High levels of impulsivity have been associated with psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and substance abuse. In addition, acute stress is known to exacerbate many psychiatric symptoms in impulse control disorders. OBJECTIVES: The purpose of the current study was to investigate the acute effects of the pharmacological stressor yohimbine on response inhibition and impulsive choice. METHODS: A group of male rats (n = 12) was trained in the delayed reward task (DRT) to assess impulsive choice. A separate group (n = 10) was trained in the stop-signal task (SST) to measure response inhibition. Upon stable responding, the effects of yohimbine (0, 1.25, 2.5, and 5 mg/kg i.p.) were tested in a Latin square design. RESULTS: Acute yohimbine significantly increased the preference for the large and delayed reinforcer in the DRT, indicating a decrease in impulsive choice. On the contrary, the effect size of 1.25 mg/kg yohimbine on stop-signal reaction times correlated negatively with baseline performance, suggesting a baseline-dependent effect on response inhibition as measured in the SST. CONCLUSIONS: The current data suggest that the effects of the pharmacological stressor yohimbine on impulse control strongly depend on the type of impulsive behavior. Pharmacological stress decreased impulsive decision making, an observation that is in line with previously published rodent studies. By contrast, the lowest dose of yohimbine revealed a baseline-dependent effect on response inhibition. As such, the effects of yohimbine are largely comparable to the effects of psychostimulants on impulsivity and may support the notion of cross sensitization of stress and psychostimulants. PMID- 27251131 TI - CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence. AB - BACKGROUND: Activation of corticotropin-releasing factor type 1 receptors (CRF R1) in the ventral tegmental area (VTA) represents a critical mechanism for social defeat to escalate cocaine self-administration in adult rats. OBJECTIVE: We determined the acute effect of a CRF-R1 antagonist (CP376395) microinfusion into the VTA prior to each episode of social defeat in adolescent rats and determined whether this drug treatment could prevent later escalation of cocaine taking in early adulthood. METHODS: Rats were implanted with bilateral cannulae aimed at the VTA 5 days before the first social defeat. Bilateral microinfusion of CP376395 (500 ng/side) or vehicle occurred 20 min before each episode of social defeat on postnatal days (P) 35, 38, 41, and 44. Behavior was quantified on P35 and P44. On P57, rats were implanted with intra-jugular catheters, and subsequent cocaine self-administration was analyzed. RESULTS: CP376395-treated adolescent rats walked less and were attacked more slowly but were socially investigated more than vehicle-treated adolescents. Vehicle-treated rats showed increased social and decreased non-social exploration from P35 to P44, while CP376395-treated rats did not. Socially defeated, vehicle-treated adolescents took more cocaine during a 24-h unlimited access binge during adulthood. The latency to supine posture on P44 was inversely correlated with later cocaine self administration during fixed and progressive ratio schedules of reinforcement and during the binge. CONCLUSIONS: CP376395 treatment in adolescence blocked escalation of cocaine taking in adulthood. Episodes of social defeat stress engender neuroadaptation in CRF-R1s in the VTA that alter coping with social stress and that persist into adulthood. PMID- 27251130 TI - Atypical antipsychotics and effects on feeding: from mice to men. AB - RATIONALE: So-called atypical antipsychotics (AAPs) are associated with varying levels of weight gain and associated metabolic disturbances, which in patients with serious mental illness (SMI) have been linked to non-compliance and poor functional outcomes. Mechanisms underlying AAP-induced metabolic abnormalities are only partially understood. Antipsychotic-induced weight gain may occur as a result of increases in food intake and/or changes in feeding. OBJECTIVE: In this review, we examine the available human and preclinical literature addressing AAP related changes in feeding behavior, to determine whether changes in appetite and perturbations in regulation of food intake could be contributing factors to antipsychotic-induced weight gain. RESULTS: In general, human studies point to disruption by AAPs of feeding behaviors and food consumption. In rodents, increases in cumulative food intake are mainly observed in females; however, changes in feeding microstructure or motivational aspects of food intake appear to occur independent of sex. CONCLUSIONS: The findings from this review indicate that the varying levels of AAP-related weight gain reflect changes in both appetite and feeding behaviors, which differ by type of AAP. However, inconsistencies exist among the studies (both human and rodent) that may reflect considerable differences in study design and methodology. Future studies examining underlying mechanisms of antipsychotic-induced weight gain are recommended in order to develop strategies addressing the serious metabolic side effect of AAPs. PMID- 27251133 TI - Is Survival for Patients with Resectable Lung Metastatic Colorectal Cancer Comparable to Those with Resectable Liver Disease? Results from the South Australian Metastatic Colorectal Registry. AB - BACKGROUND: Hepatic resection for colorectal (CRC) metastasis is considered a standard of care. Resection of metastasis isolated to lung also is considered potentially curable, although there is still some variation in recommendations. We explore outcomes for patients undergoing lung resection for mCRC, with the liver resection group as the comparator. METHODS: South Australian (SA) metastatic CRC registry data were analysed to assess patient characteristics and survival outcomes for patients suitable for lung or liver resection. RESULTS: A total of 3241 patients are registered on the database to December 2014. One hundred two (3.1 %) patients were able to undergo a lung resection compared with 420 (12.9 %) who had a liver resection. Of the lung resection patients, 62 (61 %) presented with lung disease only, 21 % initially presented with liver disease only, 11 % had both lung and liver, and 7 % had brain or pelvic disease resection. Of these patients, 79 % went straight to surgery without any neoadjuvant treatment and 34 % had lung resection as the only intervention. Chemotherapy for metastatic disease was given more often to liver resection patients: 76.9 versus 53.9 %, p = 0.17. Median overall survival is 5.6 years for liver resection and has not been reached for lung resection (hazard ratio 0.82, 95 % confidence interval 0.54-1.24, p = 0.33). CONCLUSIONS: Lung resection was undertaken in 3.1 % of patients with mCRC in our registry. These data provide further support for long-term survival after lung resection in mCRC, survival that is at least comparable to those who undergo resection for liver metastasis in mCRC. PMID- 27251132 TI - Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-beta-mediated Akt/GSK-3beta/SNAIL 1 signalling pathway. AB - BACKGROUND: Multi-walled carbon nanotubes (MWCNT) are currently under intense toxicological investigation due to concern on their potential health effects. Current in vitro and in vivo data indicate that MWCNT exposure is strongly associated with lung toxicity (inflammation, fibrosis, granuloma, cancer and airway injury) and their effects might be comparable to asbestos-induced carcinogenesis. Although fibrosis is a multi-origin disease, epithelial mesenchymal transition (EMT) is recently recognized as an important pathway in cell transformation. It is known that MWCNT exposure induces EMT through the activation of the TGF-beta/Smad signalling pathway thus promoting pulmonary fibrosis, but the molecular mechanisms involved are not fully understood. In the present work we propose a new mechanism involving a TGF-beta-mediated signalling pathway. METHODS: Human bronchial epithelial cells were incubated with two different MWCNT samples at various concentrations for up to 96 h and several markers of EMT were investigated. Quantitative real time PCR, western blot, immunofluorescent staining and gelatin zymographies were performed to detect the marker protein alterations. ELISA was performed to evaluate TGF-beta production. Experiments with neutralizing anti-TGF-beta antibody, specific inhibitors of GSK 3beta and Akt and siRNA were carried out in order to confirm their involvement in MWCNT-induced EMT. In vivo experiments of pharyngeal aspiration in C57BL/6 mice were also performed. Data were analyzed by a one-way ANOVA with Tukey's post-hoc test. RESULTS: Fully characterized MWCNT (mean length < 5 MUm) are able to induce EMT in an in vitro human model (BEAS-2B cells) after long-term incubation at sub cytotoxic concentrations. MWCNT stimulate TGF-beta secretion, Akt activation and GSK-3beta inhibition, which induces nuclear accumulation of SNAIL-1 and its transcriptional activity, thus contributing to switch on the EMT program. Moreover, a significant increment of nuclear beta-catenin - due to E-cadherin repression and following translocation to nucleus - likely reinforces signalling for EMT promotion. In vivo results supported the occurrence of pulmonary fibrosis following MWCNT exposure. CONCLUSIONS: We demonstrate a new molecular mechanism of MWCNT-mediated EMT, which is Smad-independent and involves TGF-beta and its intracellular effectors Akt/GSK-3beta that activate the SNAIL-1 signalling pathway. This finding suggests potential novel targets in the development of therapeutic and preventive approaches. PMID- 27251134 TI - Radiation Therapy is Associated with Improved Outcomes in Merkel Cell Carcinoma. AB - BACKGROUND: Following wide excision of Merkel cell carcinoma (MCC), postoperative radiation therapy (RT) is typically recommended. Controversy remains as to whether RT can be avoided in selected cases, such as those with negative margins. Additionally, there is evidence that RT can influence survival. METHODS: We included 171 patients treated for non-metastatic MCC from 1994 through 2012 at a single institution. Patients without pathologic nodal evaluation (clinical N0 disease) were excluded to reflect modern treatment practice. The endpoints included local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and disease-specific survival (DSS). RESULTS: Median follow-up was 33 months. Treatment with RT was associated with improved 3 year LC (91.2 vs. 76.9 %, respectively; p = 0.01), LRC (79.5 vs. 59.1 %; p = 0.004), DFS (57.0 vs. 30.2 %; p < 0.001), and OS (73 vs. 66 %; p = 0.02), and was associated with improved 3-year DSS among node-positive patients (76.2 vs. 48.1 %; p = 0.035), but not node-negative patients (90.1 vs. 80.8 %; p = 0.79). On multivariate analysis, RT was associated with improved LC [hazard ratio (HR) 0.18, 95 % confidence interval (CI) 0.07-0.46; p < 0.001], LRC (HR 0.28, 95 % CI 0.14-0.56; p < 0.001), DFS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001), OS (HR 0.53, 95 % CI 0.31-0.93; p = 0.03), and DSS (HR 0.42, 95 % CI 0.26-0.70; p = 0.001). Patients with negative margins had significant improvements in 3-year LC (90.1 vs. 75.4 %; p < 0.001) with RT. Deaths not attributable to MCC were relatively evenly distributed between the RT and no RT groups (28.5 and 29.3 % of patients, respectively). CONCLUSIONS: RT for MCC was associated with improved LRC and survival. RT appeared to be beneficial regardless of margin status. PMID- 27251135 TI - Treatment Interval between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer Patients: A Population-Based Study. AB - BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) has been widely implemented in the treatment of rectal cancer patients, but optimal timing of surgery after neoadjuvant therapy is unclear. The purpose of this study was to evaluate the effects of prolonged intervals between long-course CRT and surgery in rectal cancer patients. METHODS: Data on all rectal cancer patients diagnosed between 2006 and 2011 were retrieved from the population-based Netherlands Cancer Registry; the main outcome parameters were pathologic complete response (pCR) and overall survival (OS). Outcomes were reported separately for patients with early tumors (ETs; N = 217) and locally advanced rectal cancer (LARC; N = 1073). Patients were divided into 2-week interval groups according to treatment interval, ranging from 5-6 to 13-14 weeks. Kaplan-Meier curves, and logistic regression and Cox regression models were used for data analysis. RESULTS: No significant difference in pCR rate was observed for ET patients according to treatment interval. Compared with a treatment interval of 7-8 weeks, pCR rates in LARC patients were higher after 9-10 weeks (18.4 %; odds ratio [OR] 1.56, 95 % CI 1.03-2.37) and 11-12 weeks of treatment interval (20.8 %; OR 1.94, 95 % CI 1.15 3.26). Treatment interval did not influence OS in ET or LARC patients. CONCLUSIONS: Treatment intervals of 9-12 weeks between surgery and CRT seem to improve the chances of pCR in LARC patients, without an effect on OS. The length of treatment interval did not affect outcomes in patients with ET. The ongoing search for minimally invasive surgery drives the need for exploration of factors that improve pathologic response. PMID- 27251137 TI - Erratum to: The association between white-matter tract abnormalities, and neuropsychiatric and cognitive symptoms in retired professional football players with multiple concussions. PMID- 27251136 TI - Crystal structure of human S100A8 in complex with zinc and calcium. AB - BACKGROUND: S100 proteins are a large family of calcium binding proteins present only in vertebrates. They function intra- and extracellularly both as regulators of homeostatic processes and as potent effectors during inflammation. Among these, S100A8 and S100A9 are two major constituents of neutrophils that can assemble into homodimers, heterodimers and higher oligomeric species, including fibrillary structures found in the ageing prostate. Each of these forms assumes specific functions and their formation is dependent on divalent cations, notably calcium and zinc. In particular, zinc appears as a major regulator of S100 protein function in a disease context. Despite this central role, no structural information on how zinc bind to S100A8/S100A9 and regulates their quaternary structure is yet available. RESULTS: Here we report two crystallographic structures of calcium and zinc-loaded human S100A8. S100A8 binds two zinc ions per homodimer, through two symmetrical, all-His tetracoordination sites, revealing a classical His-Zn binding mode for the protein. Furthermore, the presence of a (Zn)2-cacodylate complex in our second crystal form induces ligand swapping within the canonical His4 zinc binding motif, thereby creating two new Zn-sites, one of which involves residues from symmetry-related molecules. Finally, we describe the calcium-induced S100A8 tetramer and reveal how zinc stabilizes this tetramer by tightening the dimer-dimer interface. CONCLUSIONS: Our structures of Zn(2+)/Ca(2+)-bound hS100A8 demonstrate that S100A8 is a genuine His-Zn S100 protein. Furthermore, they show how zinc stabilizes S100A8 tetramerization and potentially mediates the formation of novel interdimer interactions. We propose that these zinc-mediated interactions may serve as a basis for the generation of larger oligomers in vivo. PMID- 27251138 TI - Microbial diversification of Diels-Alder cycloadducts by whole cells of Penicillium brasilianum. AB - Functionalizations of cycloadducts are important steps for the use of Diels-Alder reactions in the construction of complex cyclic or polycyclic molecules from relatively simple starting materials. In the present work, we studied the ability of Penicillium brasilianum to perform microbial transformations of racemic Diels Alder endo-cycloadducts. Thus, Diels-Alder products, obtained from reacting cyclopentadiene or 2,3-dimethylbutadiene with alkylated para-benzoquinones, were transformed by the resting cells of P. brasilianum producing new functionalized polycyclic compounds. These biotransformations yielded novel products of oxidation and ring closure, reduction of the C=C or C=O in [Formula: see text] unsaturated system, and allylic hydroxylations. The reduction products (conjugated double bond and carbonyl group) were also synthesized, and the enantioselectivity of both in vitro and in vivo processes was evaluated. In all cases, the microbiological transformations were enantioselective. In silico docking studies of the Diels-Alder cycloadducts with P. brasilianum oxidoreductase "old yellow enzymes" shed more light on these transformations. PMID- 27251139 TI - Experimental and theoretical correlations between vanadium K-edge X-ray absorption and Kbeta emission spectra. AB - A series of vanadium compounds was studied by K-edge X-ray absorption (XAS) and K[Formula: see text] X-ray emission spectroscopies (XES). Qualitative trends within the datasets, as well as comparisons between the XAS and XES data, illustrate the information content of both methods. The complementary nature of the chemical insight highlights the success of this dual-technique approach in characterizing both the structural and electronic properties of vanadium sites. In particular, and in contrast to XAS or extended X-ray absorption fine structure (EXAFS), we demonstrate that valence-to-core XES is capable of differentiating between ligating atoms with the same identity but different bonding character. Finally, density functional theory (DFT) and time-dependent DFT calculations enable a more detailed, quantitative interpretation of the data. We also establish correction factors for the computational protocols through calibration to experiment. These hard X-ray methods can probe vanadium ions in any oxidation or spin state, and can readily be applied to sample environments ranging from solid-phase catalysts to biological samples in frozen solution. Thus, the combined XAS and XES approach, coupled with DFT calculations, provides a robust tool for the study of vanadium atoms in bioinorganic chemistry. PMID- 27251141 TI - New method for accurate estimations of LV function for small hearts. PMID- 27251140 TI - Bis(hinokitiolato)zinc complex ([Zn(hkt)2]) activates Akt/protein kinase B independent of insulin signal transduction. AB - Since many Zn complexes have been developed to enhance the insulin-like activity and increase the exposure and residence of Zn in the animal body, these complexes are recognized as one of the new candidates with action mechanism different from existing anti-diabetic drugs. However, the molecular mechanism by which Zn complexes exert an anti-DM effect is unknown. Therefore, we evaluated the activity of Zn complexes, especially related to the phosphorylation of insulin signaling pathway components. We focused on the insulin-like effects of the bis(hinokitiolato)zinc complex, [Zn(hkt)2], using 3T3-L1 adipocytes. [Zn(hkt)2] was taken up by cells and induced Akt phosphorylation in a time-dependent manner. Additionally, it showed inhibitory activity against PTP1B and PTEN, which are major negative regulators of insulin signaling. It did not promote the phosphorylation of IR (insulin receptor)-beta or IRS (insulin receptor substrate) 1 by itself, but in combination with insulin, it enhanced the phosphorylation of IRbeta. We conclude that [Zn(hkt)2] has effects on the proteins of insulin signaling pathway without insulin receptor mediation, and [Zn(hkt)2] promotes insulin function and shows the anti-DM effects. Thus, [Zn(hkt)2] may be the basis for improved DM treatments. PMID- 27251142 TI - Impact of integrating heart rate response with perfusion imaging on the prognostic value of regadenoson SPECT myocardial perfusion imaging in patients with end-stage renal disease. AB - BACKGROUND: We investigated whether integrating heart rate response (HRR) to regadenoson with myocardial perfusion imaging (MPI) analysis can enhance risk prediction in end-stage renal disease (ESRD) patients. METHODS AND RESULTS: We prospectively followed 303 ESRD patients after regadenoson stress MPI for a mean of 35 months. Normal HRR to regadenoson was defined as >=28% increase from baseline. Normal MPI was defined as a summed stress score <=3 and left ventricular ejection fraction >=50%. The study cohort was divided in four groups based on various combinations of normal/abnormal HRR and MPI. There was a step wise increase in the risk of primary endpoint of all-cause death and the composite secondary endpoint of cardiac death or myocardial infarction; patients with Normal MPI/Normal HRR had the lowest event rates and those with Abnormal MPI/Abnormal HRR had the highest, whereas subjects with Abnormal MPI/Normal HRR and Normal MPI/Abnormal HRR had intermediate event rates. This pattern was maintained after adjusting for important clinical covariates. CONCLUSION: In ESRD patients, integrating HRR to vasodilator stress with MPI interpretation improves risk stratification. Normal HRR/Normal MPI identify truly low-risk group, whereas abnormal MPI or abnormal HRR portrays elevated risk. PMID- 27251144 TI - A quick glance at selected topics in this issue. PMID- 27251143 TI - Correction of collimator-dependent differences in the heart-to-mediastinum ratio in 123I-metaiodobenzylguanidine cardiac sympathetic imaging: Determination of conversion equations using point-source imaging. AB - BACKGROUND: Septal penetration causes collimator-dependent differences in the heart-to-mediastinum (H/M) ratio in 123I-metaiodobenzylguanidine (MIBG) cardiac imaging. We investigated generally applicable methods to correct such differences. METHODS AND RESULTS: Four hours after 123I-MIBG injection, 40 patients underwent anterior chest imaging successively with medium-energy (ME) and various non-ME collimators. The H/M ratios obtained with the non-ME collimators before and after 123I-dual-window penetration correction were compared with the ME-derived standard values to determine patient-based conversion equations for empiric and combined corrections, respectively. A 123I point source was imaged with various collimators, and the central ratio, the ratio of count in a small central region of interest to count in a large one, was calculated. The method of predicting the conversion equations from the central ratios was determined. Correction using the patient-based conversion equations removed systematic underestimation of the H/M ratios obtained with the non-ME collimators, and combined correction depressed residual random errors to some degree. Point-source-based equations yielded results comparable to the patient based equations. CONCLUSIONS: Empiric and combined corrections effectively reduce collimator-dependent differences in the H/M ratio. The conversion equations can be predicted from simple point-source imaging, which would allow to apply these corrections to data obtained with various collimators. PMID- 27251145 TI - Targeting activated macrophages to identify the vulnerable atherosclerotic plaque. PMID- 27251146 TI - Evaluation of myocardial sympathetic innervation in the 21st century: Is there a role for planar 123I-MIBG imaging? PMID- 27251147 TI - The role and clinical effectiveness of multimodality imaging in the management of cardiac complications of cancer and cancer therapy. AB - With the increasing number of individuals living with a current or prior diagnosis of cancer, it is important for the cardiovascular specialist to recognize the various complications of cancer and its therapy on the cardiovascular system. This is true not only for established cancer therapies, such as anthracyclines, that have well established cardiovascular toxicities, but also for the new targeted therapies that can have "off target" effects in the heart and vessels. The purpose of this informational statement is to provide cardiologists, cardiac imaging specialists, cardio-oncologists, and oncologists an understanding of how multimodality imaging may be used in the diagnosis and management of the cardiovascular complications of cancer therapy. In addition, this document is meant to provide useful general information concerning the cardiovascular complications of cancer and cancer therapy as well as established recommendations for the monitoring of specific cardiotoxic therapies. PMID- 27251150 TI - Specialists attack drug agency's fast track approval scheme. PMID- 27251149 TI - Bioimpedance cardiography in pregnancy: A longitudinal cohort study on hemodynamic pattern and outcome. AB - BACKGROUND: Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child. Bioimpedance cardiography may provide additional outcome-relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases. METHODS: We performed a prospective longitudinal cohort trial in an outpatient setting and included 242 pregnant women. Cardiac output and concomitant hemodynamic data were recorded from 11(th)-13(th) week of gestation every 5(th) week as well as at two occasions post partum employing bioimpedance cardiography. RESULTS: Cardiac output increased during pregnancy and peaked early in the third trimester. A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes. Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy. Furthermore, an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis. CONCLUSIONS: Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein. These may be altered in women at risk for preeclampsia or reduced birthweigth. The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks. PMID- 27251151 TI - Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes. AB - BACKGROUND: Positive associations have been observed between cardiovascular disease (CVD) and type 2 diabetes mellitus (DM), but their causal relationship has not been clarified. Nevertheless, guidelines from relevant medical societies recommend using cholesterol lowering medication (statin) for both types of patients. Medicines with several different action mechanisms have been developed, and the effectiveness of different lifestyle modifications has been studied extensively for the prevention of DM, which was successful in improving clinical marker status in relatively short-term treatments, but none have been shown to be effective in improving long-term outcomes (mortality from CVD and all causes). SUMMARY: Statin-induced suppression of prenyl intermediates in the cholesterol biosynthetic pathway has been linked to stimulated atherosclerosis and heart failure. On the other hand, certain types of vegetable oil and hydrogenated oil shortened the survival of stroke-prone spontaneously hypertensive rats by decreasing platelet number, increasing hemorrhagic tendency and damaging kidney functions, which could not be accounted for by their fatty acid and phytosterol compositions. These vegetable oils and medicines such as statin and warfarin share, in part, a common mechanism to inhibit vitamin K2-dependent processes, which was interpreted to lead to increased onset of CVD, DM, chronic kidney disease, bone fracture and even mental disorder. Impaired vitamin K2-dependent processes by some types of vegetable oils and medicines, but not plasma high low density lipoprotein cholesterol, were proposed as the cause of CVD, DM and other lifestyle-related diseases. High n-6/n-3 fatty acid ratio of ingested foods, but not animal fats, was emphasized to be another risk factor for many of the diseases described above. KEY MESSAGES: To date, no randomized controlled trials (RCTs) have been performed to prove the above interpretation. However, the opposite types of RCT trials have been performed by increasing the intake of high linoleic vegetable oils and reducing that of animal fats, which resulted in increased CVD and all-cause mortality. The amounts of these vegetable oils to exhibit adverse effects in animal studies are not huge (<6 energy %), which should not be overlooked nor disregarded. PMID- 27251148 TI - Dermacentor reticulatus: a vector on the rise. AB - Dermacentor reticulatus is a hard tick species with extraordinary biological features. It has a high reproduction rate, a rapid developmental cycle, and is also able to overcome years of unfavourable conditions. Dermacentor reticulatus can survive under water for several months and is cold-hardy even compared to other tick species. It has a wide host range: over 60 different wild and domesticated hosts are known for the three active developmental stages. Its high adaptiveness gives an edge to this tick species as shown by new data on the emergence and establishment of D. reticulatus populations throughout Europe. The tick has been the research focus of a growing number of scientists, physicians and veterinarians. Within the Web of Science database, more than a fifth of the over 700 items published on this species between 1897 and 2015 appeared in the last three years (2013-2015). Here we attempt to synthesize current knowledge on the systematics, ecology, geographical distribution and recent spread of the species and to highlight the great spectrum of possible veterinary and public health threats it poses. Canine babesiosis caused by Babesia canis is a severe leading canine vector-borne disease in many endemic areas. Although less frequently than Ixodes ricinus, D. reticulatus adults bite humans and transmit several Rickettsia spp., Omsk haemorrhagic fever virus or Tick-borne encephalitis virus. We have not solely collected and reviewed the latest and fundamental scientific papers available in primary databases but also widened our scope to books, theses, conference papers and specialists colleagues' experience where needed. Besides the dominant literature available in English, we also tried to access scientific literature in German, Russian and eastern European languages as well. We hope to inspire future research projects that are necessary to understand the basic life-cycle and ecology of this vector in order to understand and prevent disease threats. We conclude that although great strides have been made in our knowledge of the eco-epidemiology of this species, several gaps still need to be filled with basic research, targeting possible reservoir and vector roles and the key factors resulting in the observed geographical spread of D. reticulatus. PMID- 27251153 TI - Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies. AB - Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call 'endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named 'exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases. PMID- 27251152 TI - Temporal association between childhood leukaemia and population growth in Swiss municipalities. AB - The population mixing hypothesis proposes that childhood leukaemia (CL) might be a rare complication of a yet unidentified subclinical infection. Large population influxes into previously isolated rural areas may foster localised epidemics of the postulated infection causing a subsequent increase of CL. While marked population growth after a period of stability was central to the formulation of the hypothesis and to the early studies on population mixing, there is a lack of objective criteria to define such growth patterns. We aimed to determine whether periods of marked population growth coincided with increases in the risk of CL in Swiss municipalities. We identified incident cases of CL aged 0-15 years for the period 1985-2010 from the Swiss Childhood Cancer Registry. Annual data on population counts in Swiss municipalities were obtained for 1980-2010. As exposures, we defined (1) cumulative population growth during a 5-year moving time window centred on each year (1985-2010) and (2) periods of 'take-off growth' identified by segmented linear regression. We compared CL incidence across exposure categories using Poisson regression and tested for effect modification by degree of urbanisation. Our study included 1500 incident cases and 2561 municipalities. The incident rate ratio (IRR) comparing the highest to the lowest quintile of 5-year population growth was 1.18 (95 % CI 0.96, 1.46) in all municipalities and 1.33 (95 % CI 0.93, 1.92) in rural municipalities (p value interaction 0.36). In municipalities with take-off growth, the IRR comparing the take-off period (>6 % annual population growth) with the initial period of low or negative growth (<2 %) was 2.07 (95 % CI 0.95, 4.51) overall and 2.99 (1.11, 8.05) in rural areas (p interaction 0.52). Our study provides further support for the population mixing hypothesis and underlines the need to distinguish take-off growth from other growth patterns in future research. PMID- 27251154 TI - Spatial transmission and meteorological determinants of tuberculosis incidence in Qinghai Province, China: a spatial clustering panel analysis. AB - BACKGROUND: Tuberculosis (TB) is the notifiable infectious disease with the second highest incidence in the Qinghai province, a province with poor primary health care infrastructure. Understanding the spatial distribution of TB and related environmental factors is necessary for developing effective strategies to control and further eliminate TB. METHODS: Our TB incidence data and meteorological data were extracted from the China Information System of Disease Control and Prevention and statistical yearbooks, respectively. We calculated the global and local Moran's I by using spatial autocorrelation analysis to detect the spatial clustering of TB incidence each year. A spatial panel data model was applied to examine the associations of meteorological factors with TB incidence after adjustment of spatial individual effects and spatial autocorrelation. RESULTS: The Local Moran's I method detected 11 counties with a significantly high-high spatial clustering (average annual incidence: 294/100 000) and 17 counties with a significantly low-low spatial clustering (average annual incidence: 68/100 000) of TB annual incidence within the examined five-year period; the global Moran's I values ranged from 0.40 to 0.58 (all P-values < 0.05). The TB incidence was positively associated with the temperature, precipitation, and wind speed (all P-values < 0.05), which were confirmed by the spatial panel data model. Each 10 degrees C, 2 cm, and 1 m/s increase in temperature, precipitation, and wind speed associated with 9 % and 3 % decrements and a 7 % increment in the TB incidence, respectively. CONCLUSIONS: High TB incidence areas were mainly concentrated in south-western Qinghai, while low TB incidence areas clustered in eastern and north-western Qinghai. Areas with low temperature and precipitation and with strong wind speeds tended to have higher TB incidences. PMID- 27251155 TI - Evaluation of a New Brain Tissue Probe for Intracranial Pressure, Temperature, and Cerebral Blood Flow Monitoring in Patients with Aneurysmal Subarachnoid Hemorrhage. AB - OBJECTIVE: To evaluate an intraparenchymal probe for intracranial pressure (ICP) and temperature (TEMP) monitoring as well as determination of cerebral hemodynamics using a near-infrared spectroscopy (NIRS) and indocyanine green (ICG) dye dilution method (NIRS-ICP probe). METHODS: The NIRS-ICP probe was applied after aneurysmal subarachnoid hemorrhage if multimodal monitoring was established due to poor neurological condition. ICP and TEMP values were obtained from ventricular catheters and systemic temperature sensors. Repeated NIRS-ICG measurements (2 injections within 30 min) were performed daily for determination of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time of ICG (mttICG). Secondary neurologic dysfunction was defined as brain tissue oxygen tension <20 mmHg and/or lactate/pyruvate ratio >35 obtained from cerebral probing. RESULTS: A total of 128 NIRS-ICG measurements were performed in ten patients. The correlation coefficients between ICP and TEMP values obtained with the NIRS-ICP probe and values from routine monitoring were r = 0.72 and r = 0.96, respectively. The mean values were 30.3 +/- 13.6 ml/100 g/min for CBF, 3.3 +/- 1.2 ml/100 g for CBV, and 6.8 +/- 1.6 s for mttICG. The coefficients of variation from repeated NIRS-ICG measurements were 10.9 % for CBF, 11.7 % for CBV, and 3.8 % for mttICG. The sensitivity for detection of secondary neurologic dysfunction was 85 % and the specificity 83 % using a CBF-threshold of 25 ml/100 g/min. CONCLUSION: Multimodal monitoring using the NIRS-ICP probe is feasible with high reproducibility of measurement values and the ability to detect secondary neurologic dysfunction. No safety concerns exist for the routine clinical use of the NIRS-ICP probe. PMID- 27251157 TI - Stimulation of cell proliferation by glutathione monoethyl ester in aged bone marrow stromal cells is associated with the assistance of TERT gene expression and telomerase activity. AB - The proliferation and differentiation potential of aged bone marrow stromal cells (BMSCs) are significantly reduced. In order to improve the performance of the aged BMSCs, these cells were treated with 2 mM glutathione monoethyl ester (GSH MEE) for 24 h. Proliferation rate, telomerase activity, telomere length, and differentiation to cholinergic neuron-like cells (CNLCs) were observed to increase. Though, the expression level of telomerase reverse transcriptase gene increased, but CTC1 and TEN1 genes from Ctc1-Stn1-Ten1 complex encoding proteins with regulatory function significantly decreased. Trypan blue exclusion assay was used to analyze the proliferation and, while telomere length, its several related gene expressions, and telomerase activity were measured using the real time reverse transcription-polymerase chain reaction and polymerase chain reaction enzyme-linked immunosorbent assay techniques, respectively. CNLCs differentiation potential was evaluated by estimating the percentage of choline acetyltransferase immunereactive cells.The results suggested that GSH-MEE could improve aged rat BMSC properties and would be of potential benefit for enhancing the performance of aged people's BMSCs. PMID- 27251156 TI - BM-MSCs and Bio-Oss complexes enhanced new bone formation during maxillary sinus floor augmentation by promoting differentiation of BM-MSCs. AB - Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been recognized as a new strategy for maxillary sinus floor elevation. However, little is known concerning the effect of the biomechanical pressure (i.e., sinus pressure, masticatory pressure, and respiration) on the differentiation of BM-MSCs and the formation of new bone during maxillary sinus floor elevation. The differentiation of BM-MSCs into osteoblasts was examined in vitro under cyclic compressive pressure using the Flexcell(r) pressure system, and by immunohistochemical analysis, qRT-PCR, and Western blot. Micro-CT was used to detect bone formation and allow image reconstruction of the entire maxillary sinus floor elevation area. Differentiation of BM-MSCs into osteoblasts was significantly increased under cyclic compressive pressure. The formation of new bone was enhanced after implantation of the pressured complex of BM-MSCs and Bio-Oss during maxillary sinus floor elevation. The pressured complex of BM-MSCs and Bio-Oss promoted new bone formation and maturation in the rabbit maxillary sinus. Stem cell therapy combined with this tissue engineering technique could be effectively used in maxillary sinus elevation and bone regeneration. PMID- 27251158 TI - Silver nanoparticles from Dendropanax morbifera Leveille inhibit cell migration, induce apoptosis, and increase generation of reactive oxygen species in A549 lung cancer cells. AB - Green synthesized silver nanoparticles have significant potential in the pharmaceutical field because of their biological functions such as antioxidant and anticancer activities. Novel silver nanoparticles synthesized from Dendropanax morbifera Leveille leaves (D-AgNPs) exhibit antimicrobial activity and reduce the viability of cancer cells without affecting the viability of RAW 264.7 macrophage-like cells. In this study, we evaluated the anticancer effect of D-AgNPs by measuring the levels of reactive oxygen species (ROS) production and toxicity against A549 and HepG2 cell lines. The effect of D-AgNPs on cell migration, induction of apoptosis, and modification of gene and/or protein expression of cancer-related markers was determined using A549 cells. D-AgNPs exhibited cytotoxicity in A549 and HepG2 cell at different concentrations and enhanced the production of ROS in both cell lines. An increase in cell apoptosis and a reduction in cell migration in A549 cells were also observed after D-AgNP treatment. Furthermore, the effect of D-AgNPs in A549 cells was shown to be related to modification of the EGFR/p38 MAPK pathway. Our data provide the first evidence supporting the potential of D-AgNPs as a possible anticancer agent, particularly for the treatment of non-small cell lung carcinoma. PMID- 27251159 TI - Quantitative comparison of cancer and normal cell adhesion using organosilane monolayer templates: an experimental study on the anti-adhesion effect of green tea catechins. AB - The main constituent of green tea, (-)-Epigallocatechin-3-O-gallate (EGCG), is known to have cancer-specific chemopreventive effects. In the present work, we investigated how EGCG suppresses cell adhesion by comparing the adhesion of human pancreatic cancer cells (AsPC-1 and BxPC-3) and their counterpart, normal human embryonic pancreas-derived cells (1C3D3), in catechin-containing media using organosilane monolayer templates (OMTs). The purpose of this work is (1) to evaluate the quantitativeness in the measurement of cell adhesion with the OMT and (2) to show how green-tea catechins suppress cell adhesion in a cancer specific manner. For the first purpose, the adhesion of cancer and normal cells was compared using the OMT. The cell adhesion in different type of catechins such as EGCG, (-)-Epicatechin-3-O-gallate (ECG) and (-)-Epicatechin (EC) was also evaluated. The measurements revealed that the anti-adhesion effect of green-tea catechins is cancer-specific, and the order is EGCG?ECG>EC. The results agree well with the data reported to date, showing the quantitativeness of the new method. For the second purpose, the contact area of cells on the OMT was measured by reflection interference contrast microscopy. The cell-OMT contact area of cancer cells decreases with increasing EGCG concentration, whereas that of normal cells remains constant. The results reveal a twofold action of EGCG on cancer cell adhesion-suppressing cell attachment to a candidate adhesion site and decreasing the contact area of the cells-and validates the use of OMT as a tool for screening cancer cell adhesion. PMID- 27251162 TI - A role for the Wnt3a/beta-catenin signaling pathway in the myogenic program of C2C12 cells. AB - The Wnt/beta-catenin signaling pathway is a key regulator of embryonic development that was first identified in drosophila. More recent work has suggested a role for this pathway in mammalian, myogenesis but this process remains to be more completely elucidated. The current study was designed to investigate the role of the Wnt3a/beta-catenin signaling module in C2C12 cell differentiation and myotube formation. Activation of the Wnt/beta-catenin pathway in differentiating myoblasts, using lithium chloride supplementation, increased both the number and size of C2C12 myotubes. On the other hand, pharmacological inhibitors of Wnt/beta-catenin signaling (IWR-1, XAV939) resulted in significant decreases in myotube length without affecting their numbers. In separate experiments, a neutralizing antibody to Wnt3a also reduced myotube length without affecting the number of myotubes formed during differentiation. Confocal imaging studies revealed that beta-catenin was primarily localized in the cytoplasmic region of undifferentiated myoblasts and differentiation resulted in its enhanced expression in myotubes. Additionally, LiCl treatment resulted in enhanced expression of beta-catenin in pre-differentiating myoblast cultures. These data suggest that Wnt3a/beta-catenin signaling plays a critical role in C2C12 cell differentiation and provides an appropriate model for elucidating its functions in more detail. PMID- 27251161 TI - Induction of specific neuron types by overexpression of single transcription factors. AB - Specific neuronal types derived from embryonic stem cells (ESCs) can facilitate mechanistic studies and potentially aid in regenerative medicine. Existing induction methods, however, mostly rely on the effects of the combined action of multiple added growth factors, which generally tend to result in mixed populations of neurons. Here, we report that overexpression of specific transcription factors (TFs) in ESCs can rather guide the differentiation of ESCs towards specific neuron lineages. Analysis of data on gene expression changes 2 d after induction of each of 185 TFs implicated candidate TFs for further ESC differentiation studies. Induction of 23 TFs (out of 49 TFs tested) for 6 d facilitated neural differentiation of ESCs as inferred from increased proportion of cells with neural progenitor marker PSA-NCAM. We identified early activation of the Notch signaling pathway as a common feature of most potent inducers of neural differentiation. The majority of neuron-like cells generated by induction of Ascl1, Smad7, Nr2f1, Dlx2, Dlx4, Nr2f2, Barhl2, and Lhx1 were GABA-positive and expressed other markers of GABAergic neurons. In the same way, we identified Lmx1a and Nr4a2 as inducers for neurons bearing dopaminergic markers and Isl1, Fezf2, and St18 for cholinergic motor neurons. A time-course experiment with induction of Ascl1 showed early upregulation of most neural-specific messenger RNA (mRNA) and microRNAs (miRNAs). Sets of Ascl1-induced mRNAs and miRNAs were enriched in Ascl1 targets. In further studies, enrichment of cells obtained with the induction of Ascl1, Smad7, and Nr2f1 using microbeads resulted in essentially pure population of neuron-like cells with expression profiles similar to neural tissues and expressed markers of GABAergic neurons. In summary, this study indicates that induction of transcription factors is a promising approach to generate cultures that show the transcription profiles characteristic of specific neural cell types. PMID- 27251160 TI - TNF-alpha and Notch signaling regulates the expression of HOXB4 and GATA3 during early T lymphopoiesis. AB - During the early thymus colonization, Notch signaling activation on hematopoietic progenitor cells (HPCs) drives proliferation and T cell commitment. Although these processes are driven by transcription factors such as HOXB4 and GATA3, there is no evidence that Notch directly regulates their transcription. To evaluate the role of NOTCH and TNF signaling in this process, human CD34+ HPCs were cocultured with OP9-DL1 cells, in the presence or absence of TNF. The use of a Notch signaling inhibitor and a protein synthesis inhibitor allowed us to distinguish primary effects, mediated by direct signaling downstream Notch and TNF, from secondary effects, mediated by de novo synthesized proteins. A low and physiologically relevant concentration of TNF promoted T lymphopoiesis in OP9-DL1 cocultures. TNF positively modulated the expression of both transcripts in a Notch-dependent manner; however, GATA3 induction was mediated by a direct mechanism, while HOXB4 induction was indirect. Induction of both transcripts was repressed by a GSK3beta inhibitor, indicating that activation of canonical Wnt signaling inhibits rather than induces their expression. Our study provides novel evidences of the mechanisms integrating Notch and TNF-alpha signaling in the transcriptional induction of GATA3 and HOXB4. This mechanism has direct implications in the control of self-renewal, proliferation, commitment, and T cell differentiation. PMID- 27251164 TI - Human Action Perception is Consistent, Flexible, and Orientation Dependent. AB - Previous research has found that observers of object-directed human action pay more attention to information regarding hand contact over information regarding spatial trajectories in action, and that processing of trajectory information is disrupted by inversion. However, observers can also flexibly modulate their attention to spatial trajectory depending on the goal or context of the actor. In Experiments 1(a) and 1b of the current research, we directly compared attention with hand and trajectory information across placing and dropping actions in order to determine whether the hand bias is always present or whether flexibility in action perception can attenuate this bias. Results demonstrated that observers attend more to hand information for placing, but attend equally to hand and trajectory information for dropping. Experiment 2 explored the role of the actor's goal in processing spatial trajectory for mimed dropping actions and non human control stimuli, and the role of goals in the inversion effect. Results indicated that goal relevance increases processing of trajectory information, and that processing of all spatial trajectories in human action is disrupted by inversion, regardless of the actor's goal. The present findings highlight the role of prediction in action perception, and suggest that human action is processed with expertise. PMID- 27251163 TI - Systemic Inflammation Is Associated With Coronary Artery Calcification and All Cause Mortality in Chronic Kidney Disease. AB - BACKGROUND: Presence of systemic inflammation in chronic kidney disease (CKD) is associated with advanced coronary artery calcification (CAC). The prognostic significance of this association, however, is unknown. We evaluated the associations between CAC, estimated glomerular filtration rate (eGFR) and all cause mortality, to determine whether the associations differ according to the presence of systemic inflammation. METHODS AND RESULTS: We followed 30,703 consecutive individuals who underwent CAC measurement for a median of 79 months (IQR, 65-96 months). Patients were categorized according to baseline CAC score (0, 1-99, 100-399 and >=400), eGFR (<45, 45-59, 60-74, 75-89, 90-104, and >=105 ml/min/1.73 m(2)) and high-sensitivity C-reactive protein (hsCRP; <2.0, and >=2.0 mg/L). Prevalence and extent of CAC were greater in those with lower eGFR and higher hsCRP accordingly, even after adjustment. Lower eGFR was strongly associated with higher CAC score (>=400), and the association was more significant in patients with higher hsCRP. The greater CAC burden was associated with worse outcome in the CKD patients (eGFR <60 ml/min/1.73 m(2)) only in those with higher hsCRP. CONCLUSIONS: Patients with low eGFR and more extensive CAC had greater risk of mortality, and associations differed according to the presence of systemic inflammation. Among the CKD patients, coronary evaluation may be considered for those with elevated hsCRP. (Circ J 2016; 80: 1644-1652). PMID- 27251165 TI - Deep Learning and Developmental Learning: Emergence of Fine-to-Coarse Conceptual Categories at Layers of Deep Belief Network. AB - In this paper, I investigate conceptual categories derived from developmental processing in a deep neural network. The similarity matrices of deep representation at each layer of neural network are computed and compared with their raw representation. While the clusters generated by raw representation stand at the basic level of abstraction, conceptual categories obtained from deep representation shows a bottom-up transition procedure. Results demonstrate a developmental course of learning from specific to general level of abstraction through learned layers of representations in a deep belief network. PMID- 27251166 TI - Olfactory Sensitivity for the Mammalian Blood Odor Component Trans-4,5-epoxy-(E) 2-decenal in CD-1 Mice. AB - Using a conditioning paradigm and an automated olfactometer, we investigated the olfactory sensitivity of CD-1 mice for the mammalian blood odor component trans 4,5-epoxy-(E)-2-decenal. We found that two of the animals significantly discriminated concentrations down to 3.0 ppt (parts per trillion) from the solvent, and three animals even successfully detected dilutions as low as 0.3 ppt. Intraspecific comparisons between the olfactory detection thresholds obtained here with those obtained in earlier studies with other odorants show that mice are extraordinarily sensitive to this blood odor component. Interspecific comparisons of olfactory detection thresholds show that human subjects are even more sensitive to trans-4,5-epoxy-(E)-2-decenal than the mice tested here. Both intra- and inter-specific comparisons suggest that neither neuroanatomical properties such as the size of the olfactory epithelium, the total number of olfactory receptor neurons, or the size of olfactory brain structures, nor genetic properties such as the number of functional olfactory receptor genes or the proportion of functional relative to the total number of olfactory receptor genes allow us to reliably predict a species' olfactory sensitivity. In contrast, the results support the notion that the behavioral relevance of an odorant rather than neuroanatomical or genetic properties may determine a species' olfactory sensitivity. PMID- 27251167 TI - Biological Form is Sufficient to Create a Biological Motion Sex Aftereffect. AB - In a series of five experiments we sought to determine what causes the biological motion sex aftereffect-adaptation of a general representation of the stimulus sex, adaptation to the motion in the stimulus, or adaptation to the form in the stimulus. The experiments showed that (a) adaptation to gendered faces and gendered full body images did not create a biological motion sex aftereffect; (b) adaptation to moving partial biological motion displays containing the most important motion cues for sex discrimination (shoulders and hips or shoulders, hips, and feet) did not create a biological motion sex aftereffect; and (c) adaptation to a static frame or shapes derived from a static frame did create a biological motion sex aftereffect. These results suggest that form information is sufficient to create a biological motion sex aftereffect and suggests that biological motion sex aftereffects may be a result of lower level rather than higher level adaptation in the visual system. PMID- 27251168 TI - Action Congruency Influences Crowding When Discriminating Biological Motion Direction. AB - Identification and discrimination of peripheral stimuli are often difficult when a few stimuli adjacent to the target are present (crowding). Our previous study showed that crowding occurs for walking direction discrimination of a biological motion stimulus. In the present study, we attempted to examine whether action congruency between the target and flankers would influence the crowding effect on biological motion stimuli. Each biological motion stimulus comprised one action (e.g., walking, throwing wastepaper, etc.) and was rotated in one of five directions around the vertical axis. In Experiment 1, observers discriminated between the directions of the target stimulus actions, which were surrounded by two flankers in the peripheral visual field. The crowding effect was stronger when the flankers performed the same action as the target and the directions differed. The congruency of action type enhanced the crowding effect in the direction-discrimination task. In Experiment 2, observers discriminated between action types of target stimuli. The crowding effect for the action-discrimination task was not modulated by the congruency of action direction. Thus, identical actions induced a larger crowding effect for action-direction discrimination, but congruent directions did not influence crowding for action-type discrimination. These results suggest that the processes involved in direction discrimination of biological motion are partially distinct from action discrimination processes. PMID- 27251169 TI - Octave Bias in Pitch Perception: The Influence of Pitch Height on Pitch Class Identification. AB - Pitch height and pitch class are different, but strictly related, percepts of music tones. To investigate the influence of pitch height in a pitch class identification task, we systematically analyzed the errors-in terms of direction and amount-committed by a group of musicians. The aim of our study was to verify the existence of constant errors in the identification of pitch classes across consecutive octaves. Stimuli were single piano tones from the C major scale executed in two consecutive octaves. Participants showed different response patterns in the two octaves. The direction of errors revealed a constant tendency to underestimate pitch classes in the lowest octave and to overestimate pitch classes in the highest octave. Thus, pitch height showed to influence pitch class identification. We called this bias "pitch class polarization", since the same pitch class was judged to be respectively lower and higher, depending on relatively low or high pitch height. PMID- 27251170 TI - Role of capsaicin-sensitive nerves and tachykinins in mast cell tryptase-induced inflammation of murine knees. AB - OBJECTIVE, DESIGN: Mast cell tryptase (MCT) is elevated in arthritic joints, but its direct effects are not known. Here, we investigated MCT-evoked acute inflammatory and nociceptive mechanisms with behavioural, in vivo imaging and immunological techniques. MATERIAL AND SUBJECTS: Neurogenic inflammation involving capsaicin-sensitive afferents, transient receptor potential vanilloid 1 receptor (TRPV1), substance P (SP), neurokinin A (NKA) and their NK1 tachykinin receptor were studied using gene-deleted mice compared to C57Bl/6 wildtypes (n = 5-8/group). TREATMENT: MCT was administered intraarticularly or topically (20 MUl, 12 MUg/ml). Capsaicin-sensitive afferents were defunctionalized with the TRPV1 agonist resiniferatoxin (RTX; 30-70-100 MUg/kg s.c. pretreatment). METHODS: Knee diameter was measured with a caliper, synovial perfusion with laser Doppler imaging, mechanonociception with aesthesiometry and weight distribution with incapacitance tester over 6 h. Cytokines and neuropeptides were determined with immunoassays. RESULTS: MCT induced synovial vasodilatation, oedema, impaired weight distribution and mechanical hyperalgesia, but cytokine or neuropeptide levels were not altered at the 6-h timepoint. Hyperaemia was reduced in RTX treated and TRPV1-deleted animals, and oedema was absent in NK1-deficient mice. Hyperalgesia was decreased in SP/NKA- and NK1-deficient mice, weight bearing impairment in RTX-pretreated, TRPV1- and NK1-deficient animals. CONCLUSIONS: MCT evokes synovial hyperaemia, oedema, hyperalgesia and spontaneous pain. Capsaicin sensitive afferents and TRPV1 receptors are essential for vasodilatation, while tachykinins mediate oedema and pain. PMID- 27251172 TI - Reciprocal regulation of farnesoid X receptor alpha activity and hepatitis B virus replication in differentiated HepaRG cells and primary human hepatocytes. AB - Hepatitis B virus (HBV) and bile salt metabolism seem tightly connected. HBV enters hepatocytes by binding to sodium taurocholate cotransporting polypeptide (NTCP), the genome of which contains 2 active farnesoid X receptor (FXR) alpha response elements that participate in HBV transcriptional activity. We investigated in differentiated HepaRG cells and in primary human hepatocytes (PHHs) effects of FXR activation on HBV replication and of infection on the FXR pathway. In HepaRG cells, FXR agonists (6-ethyl chenodeoxycholic acid and GW4064), but no antagonist, and an FXR-unrelated bile salt inhibited viral mRNA, DNA, and protein production (IC50, 0.1-0.5 MUM) and reduced covalently closed circular DNA pool size. These effects were independent of the NTCP inhibitor cyclosporine-A, which suggests inhibition occurred at a postentry step. Similar results were obtained in PHHs with GW4064. Infection of these cells increased expression of FXR and modified expression of FXR-regulated genes SHP, APOA1, NTCP, CYP7A1, and CYP8B1 with a more pronounced effect in PHHs than in HepaRG cells. FXR agonists reversed all but one of the HBV-induced FXR gene profile modifications. HBV replication and FXR regulation seem to be interdependent, and altered bile salt metabolism homeostasis might contribute to the persistence of HBV infection.-Radreau, P., Porcherot, M., Ramiere, C., Mouzannar, K., Lotteau, V., Andre, P. Reciprocal regulation of farnesoid X receptor alpha activity and hepatitis B virus replication in differentiated HepaRG cells and primary human hepatocytes. PMID- 27251173 TI - Down-regulation of Risa improves insulin sensitivity by enhancing autophagy. AB - It has been reported that some small noncoding RNAs are involved in the regulation of insulin sensitivity. However, whether long noncoding RNAs also participate in the regulation of insulin sensitivity is still largely unknown. We identified and characterized a long noncoding RNA, regulator of insulin sensitivity and autophagy (Risa), which is a poly(A)(+) cytoplasmic RNA. Overexpression of Risa in mouse primary hepatocytes or C2C12 myotubes attenuated insulin-stimulated phosphorylation of insulin receptor, Akt, and Gsk3beta, and knockdown of Risa alleviated insulin resistance. Further studies showed that overexpression of Risa in hepatocytes or myotubes decreased autophagy, and knockdown of Risa up-regulated autophagy. Moreover, knockdown of Atg7 or -5 significantly inhibited the effect of knockdown of Risa on insulin resistance, suggesting that knockdown of Risa alleviated insulin resistance via enhancing autophagy. In addition, tail vein injection of adenovirus to knock down Risa enhanced insulin sensitivity and hepatic autophagy in both C57BL/6 and ob/ob mice. Taken together, the data demonstrate that Risa regulates insulin sensitivity by affecting autophagy and suggest that Risa is a potential target for treating insulin-resistance-related diseases.-Wang, Y., Hu, Y., Sun, C., Zhuo, S., He, Z., Wang, H., Yan, M., Liu, J., Luan, Y., Dai, C., Yang, Y., Huang, R., Zhou, B., Zhang, F., Zhai, Q. Down-regulation of Risa improves insulin sensitivity by enhancing autophagy. PMID- 27251174 TI - Radiographic, antibacterial and bond-strength effects of radiopaque caries tagging. AB - Selectively excavated carious lesions remain radiographically detectable. Radiopaque tagging could resolve the resulting diagnostic uncertainty. We aimed to evaluate if tagging depends on lesions depths, is antibacterial, or affects dentin bond-strengths. Artificial lesions (depth-range: 152-682 MUm, n = 34/group) were induced in human dentin samples, evaluated using wavelength independent microradiography, treated with one of two tagging materials (70% SnCl2, 30% SnF2) and re-evaluated. To evaluate antimicrobial effects, 40 dentin samples were submitted to a Lactobacillus rhamnosus invasion-model. Infected samples were treated with placebo, 0.2% chlorhexidine, SnCl2, SnF2 (n = 10/group). Dentin was sampled and colony-forming units/mg determined. Micro tensile bond-strengths of adhesive restorations (OptiBond FL, Filtek Z250) to tagged or untagged, sound and carious dentin were assessed (n = 12/group). Tagged surfaces were evaluated microscopically and via energy-dispersive X-ray spectroscopy (EDS). Tagging effects of both materials decreased with increasing lesion depths (p < 0.001). Un-/chlorhexidine-treated dentin contained significantly more viable bacteria (median 7.3/3.7 * 10(5) CFU/mg) than tagged dentin (no CFU detectable, p < 0.001). Tagging decreased bond strengths (p < 0.001) on sound (-22%/-33% for SnCl2/SnF2) and carious dentin (-50%/-54%). This might be due to widespread tin chloride or fluoride precipitation, as detected via microscopy and EDS. While radiopaque tagging seems beneficial, an optimized application protocol needs to be developed prior clinical use. PMID- 27251171 TI - Red cell DAMPs and inflammation. AB - Intravascular hemolysis, or the destruction of red blood cells in the circulation, can occur in numerous diseases, including the acquired hemolytic anemias, sickle cell disease and beta-thalassemia, as well as during some transfusion reactions, preeclampsia and infections, such as those caused by malaria or Clostridium perfringens. Hemolysis results in the release of large quantities of red cell damage-associated molecular patterns (DAMPs) into the circulation, which, if not neutralized by innate protective mechanisms, have the potential to activate multiple inflammatory pathways. One of the major red cell DAMPs, heme, is able to activate converging inflammatory pathways, such as toll like receptor signaling, neutrophil extracellular trap formation and inflammasome formation, suggesting that this DAMP both activates and amplifies inflammation. Other potent DAMPs that may be released by the erythrocytes upon their rupture include heat shock proteins (Hsp), such as Hsp70, interleukin-33 and Adenosine 5' triphosphate. As such, hemolysis represents a major inflammatory mechanism that potentially contributes to the clinical manifestations that have been associated with the hemolytic diseases, such as pulmonary hypertension and leg ulcers, and likely plays a role in specific complications of sickle cell disease such as endothelial activation, vaso-occlusive processes and tissue injury. PMID- 27251175 TI - Sulodexide for treating venous leg ulcers. AB - BACKGROUND: Venous leg ulcers are common, chronic wounds caused by venous diseases, with a high recurrence rate and heavy disease burden. Compression therapy (bandages or stockings) is the first choice treatment for venous leg ulcers. However, when ulcers remain unhealed, medication can also be used with or without compression therapy. Sulodexide, a highly purified glycosaminoglycan (a naturally occurring molecule) has antithrombotic and profibrinolytic properties (it reduces the formation of blood clots) as well as anti-inflammatory effects. Sulodexide has been studied as a potential treatment for venous leg ulcers. OBJECTIVES: To assess the efficacy and safety of sulodexide for treating venous leg ulcers. SEARCH METHODS: In July 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; Chinese Biomedical Literature Database (CBM); China National Knowledge Infrastructure Database (CNKI); Wan Fang and VIP. We also searched clinical trials registries to identify ongoing studies, as well as references listed in relevant publications. There were no restrictions based on date of publication, language or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving people with a diagnosis of venous leg ulcers which compared sulodexide with placebo or any other drug therapy (such as pentoxifylline, flavonoids, aspirin), with or without compression therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The authors independently selected studies, extracted data and assessed risk of bias. We pooled data to present the risk ratio (RR) with 95% confidence interval (CI), or presented a narrative summary. We assessed overall evidence quality according to the GRADE approach. MAIN RESULTS: We included four RCTs with a total of 463 participants (aged 42 years to 93 years); one report was only available as a published abstract.Meta-analysis of three RCTs suggests an increase in the proportion of ulcers completely healed with sulodexide as an adjuvant to local treatment (including wound care and compression therapy) compared with local treatment alone (rate of complete healing with sulodexide 49.4% compared with 29.8% with local treatment alone; RR 1.66; 95% CI 1.30 to 2.12). This evidence for sulodexide increasing the rate of complete healing is low quality due to risk of bias. It is unclear whether sulodexide is associated with any increase in adverse events (4.4% with sulodexide versus 3.1% with no sulodexide; RR 1.44; 95% CI 0.48 to 4.34). The evidence for adverse events is very low quality, downgraded twice for risk of bias and once for imprecision. AUTHORS' CONCLUSIONS: Sulodexide may increase the healing of venous ulcers, when used alongside local wound care, however the evidence is only low quality and the conclusion is likely to be affected by new research. It is not clear whether sulodexide is associated with adverse effects. The standard dosage, route and frequency of sulodexide reported in the trials was unclear. Further rigorous, adequately powered RCTs examining the effects of sulodexide on healing, ulcer recurrence, quality of life and costs are necessary. PMID- 27251177 TI - Arterial Stiffness: Is This a Marker for the Current Status or Future? PMID- 27251176 TI - Brachial-Ankle Pulse Wave Velocity is Associated with Composite Carotid and Coronary Atherosclerosis in a Middle-Aged Asymptomatic Population. AB - AIM: Although arterial stiffness has been associated with the development of atherosclerosis, the role of brachial-ankle pulse wave velocity (baPWV) for diagnosing composite coronary and carotid atherosclerosis has not been completely elucidated. METHOD: We enrolled 773 asymptomatic individuals who were referred from 25 public health centers in Seoul and who underwent carotid ultrasonography and coronary computed tomography. Non-invasive hemodynamic parameters, including baPWV, were also measured. Composite coronary and carotid atherosclerosis was defined as follows: 1) coronary artery calcium (CAC) score >= 100, 2) coronary artery stenosis (CAS) >= 50% of diameter stenosis, 3) carotid intima medial thickness (CIMT) >= 0.9 mm, or 4) presence of carotid artery plaque (CAP). RESULTS: The incidence of composite coronary and carotid atherosclerosis was 28.2%. Coronary atherosclerosis (CAC and CAS) was significantly associated with carotid atherosclerosis (CIMT and CAP). Subjects with higher baPWV (highest quartile) had a higher prevalence of composite coronary and carotid atherosclerosis (p<.001). Although multivariate analysis failed to show baPWV as an independent predictor for composite atherosclerosis, baPWV had moderate diagnostic power to detect a subject with more than two positive subclinical atherosclerosis exams [area under the curve (AUC), 0.692]. CONCLUSION: baPWV was associated with the composite coronary and carotid atherosclerotic burden in a community-based asymptomatic population. PMID- 27251180 TI - Impact of post-processing methods on apparent diffusion coefficient values. AB - OBJECTIVE: The apparent diffusion coefficient (ADC) is increasingly used as a quantitative biomarker in oncological imaging. ADC calculation is based on raw diffusion-weighted imaging (DWI) data, and multiple post-processing methods (PPMs) have been proposed for this purpose. We investigated whether PPM has an impact on final ADC values. METHODS: Sixty-five lesions scanned with a standardized whole-body DWI-protocol at 3 T served as input data (EPI-DWI, b values: 50, 400 and 800 s/mm2). Using exactly the same ROI coordinates, four different PPM (ADC_1-ADC_4) were executed to calculate corresponding ADC values, given as [10-3 mm2/s] of each lesion. Statistical analysis was performed to intra individually compare ADC values stratified by PPM (Wilcoxon signed-rank tests: alpha = 1 %; descriptive statistics; relative difference/?; coefficient of variation/CV). RESULTS: Stratified by PPM, mean ADCs ranged from 1.136-1.206 *10 3 mm2/s (? = 7.0 %). Variances between PPM were pronounced in the upper range of ADC values (maximum: 2.540-2.763 10-3 mm2/s, ? = 8 %). Pairwise comparisons identified significant differences between all PPM (P <= 0.003; mean CV = 7.2 %) and reached 0.137 *10-3 mm2/s within the 25th-75th percentile. CONCLUSION: Altering the PPM had a significant impact on the ADC value. This should be considered if ADC values from different post-processing methods are compared in patient studies. KEY POINTS: * Post-processing methods significantly influenced ADC values. * The mean coefficient of ADC variation due to PPM was 7.2 %. * To achieve reproducible ADC values, standardization of post-processing is recommended. PMID- 27251178 TI - Construction of a disulfide-stabilized diabody against fibroblast growth factor-2 and the inhibition activity in targeting breast cancer. AB - Fibroblast growth factor-2 (FGF-2) is one of the most important angiogenic factors to promote tumor growth, progression and metastasis. Neutralizing antibodies against FGF-2 may suppress the growth of tumor cells by blocking the FGF-2 signaling pathway. In this study, a disulfide-stabilized diabody (ds Diabody) that specifically targets FGF-2 was designed. Compared to its parent antibody, the introduction of disulphide bonds in the diabody could significantly increase the stability of ds-Diabody and maintain its antigen binding activity. The ds-Diabody against FGF-2 could effectively inhibit the tube formation and migration of vascular endothelial cells and block the proliferation and invasion of human breast cancer cells. In the mouse model of breast cancer xenograft tumors, the ds-Diabody against FGF-2 could significantly inhibit the growth of tumor cells. Moreover, the densities of microvessels stained with CD31 and lymphatic vessels stained with LYVE1 in tumors showed a significant decrease following treatment with the ds-Diabody against FGF-2. Our data indicated that the ds-Diabody against FGF-2 could inhibit tumor angiogenesis, lymphangiogenesis and tumor growth. PMID- 27251181 TI - Erratum to: A retrospective, semi-quantitative image quality analysis of cone beam computed tomography (CBCT) and MSCT in the diagnosis of distal radius fractures. PMID- 27251179 TI - Psychosocial predictors of treatment outcome for trauma-affected refugees. AB - BACKGROUND: The effects of treatment in trials with trauma-affected refugees vary considerably not only between studies but also between patients within a single study. However, we know little about why some patients benefit more from treatment, as few studies have analysed predictors of treatment outcome. OBJECTIVE: The objective of the study was to examine possible psychosocial predictors of treatment outcome for trauma-affected refugees. METHOD: The participants were 195 adult refugees with posttraumatic stress disorder (PTSD) who were enrolled in a 6- to 7-month treatment programme at the Competence Centre for Transcultural Psychiatry (CTP), Denmark. The CTP Predictor Index used in the study included 15 different possible outcome predictors concerning the patients' past, chronicity of mental health problems, pain, treatment motivation, prerequisites for engaging in psychotherapy, and social situation. The primary outcome measure was PTSD symptoms measured on the Harvard Trauma Questionnaire (HTQ). Other outcome measures included the Hopkins Symptom Check List-25, the WHO 5 Well-being Index, Sheehan Disability Scale, Hamilton Depression and Anxiety Scales, the somatisation scale of the Symptoms Checklist-90, Global Assessment of Functioning scales, and pain rated on visual analogue scales. The relations between treatment outcomes and the total score as well as subscores of the CTP Predictor Index were analysed. RESULTS: Overall, the total score of the CTP Predictor Index was significantly correlated to pre- to post treatment score changes on the majority of the ratings mentioned above. While employment status was the only single item significantly correlated to HTQ-score changes, a number of single items from the CTP Predictor Index correlated significantly with changes in depression and anxiety symptoms, but the size of the correlation coefficients were modest. CONCLUSIONS: The total score of the CTP Predictor Index correlated significantly with outcomes on most of the rating scales, but correlations were modest in size, possibly due to the number of different factors influencing treatment outcome. PMID- 27251182 TI - Sustainable Financing of Innovative Therapies: A Review of Approaches. AB - The process of innovation is inherently complex, and it occurs within an even more complex institutional environment characterized by incomplete information, market power, and externalities. There are therefore different competing approaches to supporting and financing innovation in medical technologies, which bring their own advantages and disadvantages. This article reviews value- and cost-based pricing, as well direct government funding, and cross-cutting institutional structures. It argues that performance-based risk-sharing agreements are likely to have little effect on the sustainability of financing; that there is a role for cost-based pricing models in some situations; and that the push towards longer exclusivity periods is likely contrary to the interests of industry. PMID- 27251184 TI - Improved overall survival for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation - A comparison of the last two decades. AB - Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (<18 yr old), who underwent SCT at our center during 1992-2002 (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched (MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute GvHD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality (HR = 0.57; p = 0.005), reduced TRM (HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic GvHD (HR = 0.49; p = 0.01), and more acute GvHD (HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT. PMID- 27251183 TI - Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations. AB - BACKGROUND: Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through meta-analytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations. METHODS: We first conducted a coordinate-based meta analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural-functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding. RESULTS: Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural-functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula's task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum's interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing. CONCLUSIONS: Collectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum). PMID- 27251185 TI - Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection. AB - BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug resistant uropathogens have pointed to the need for safe and effective UTI prevention strategies such as cranberry consumption. OBJECTIVE: We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs. DESIGN: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time. RESULTS: The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914). CONCLUSION: The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021. PMID- 27251186 TI - Why don't more people eat breakfast? A biological perspective. PMID- 27251187 TI - Reply to SL Buckner et al. PMID- 27251188 TI - Challenging the claim that intake of krill oil is associated with increased metabolic risk in overweight men. PMID- 27251189 TI - Reply to N Hoem. PMID- 27251191 TI - Views of Australian dental practitioners towards rural recruitment and retention: a descriptive study. AB - BACKGROUND: Despite an increase in the supply of dental practitioners in Australia in recent years, there remains an unequal distribution of dental practitioners with more dental practitioners working in city areas. This is in part due to difficulties in attracting and retaining dental practitioners to rural practice. The aim of this study was to investigate the attitudes of Australian dental practitioners towards what may attract them to rural areas and why they may remain in them. METHOD: A descriptive study, utilising telephone, semi-structured interviews with dental practitioners across Australia. Dental practitioners were recruited through their professional associations. Data were analysed using content and thematic analysis. RESULTS: Fifty participants; 34 dentists, eight oral health therapists, and eight dental prosthetists working in rural and urban areas of Australia. Four main themes were identified: Business Case: concerns related to income and employment security, Differences in Clinical Practices: differences in clinical treatments and professional work, Community: fitting in and belonging in the area in which you live and work, and Individual Factors: local area provision for lifestyle choices and circumstances. The most influential of these themes were business case and individual factors. Smaller rural areas, due to low populations and being unable to provide individuals with their lifestyle needs were considered unappealing for dental practitioners to live. Previous experience of rural areas was highly influential. CONCLUSIONS: The main factors influencing rural recruitment and retention were income sustainability and employment security, and individual factors. Dental practitioners felt that it was harder to earn a sustainable income and provide quality lifestyles for their family in rural areas. Previous experience of rural areas was influential towards long-term rural retention. These factors should be considered in order to develop effective strategies to address the unequal distribution of dental practitioners. PMID- 27251192 TI - Optical coherence tomography manifestations of primary vitreoretinal lymphoma. AB - BACKGROUND: Primary vitreoretinal lymphoma (PVRL), a subset of primary central nervous system lymphoma (PCNSL), is a high-grade malignant tumor that shows various chorioretinal findings. Optical coherence tomography (OCT) is useful for detecting these lesions, and various abnormalities on OCT images have been reported. The purpose of this report was to investigate retrospectively the OCT manifestations of various disease stages and compare the manifestations of pretreatment, recurrent, and chronic cases. METHODS: We reviewed the medical charts and OCT images of 38 consecutive cases with PVRL. When abnormalities were detected on OCT images, the patients were classified based on the treatment of the primary disease: pretreatment if not treated, recurrent if treated previously, and chronic when chronic changes. RESULTS: Twenty-six eyes (20 cases) had abnormalities in the post-pole OCT images, i.e., 16 eyes (12 cases) were in the pretreatment group, seven eyes (five cases) were in the recurrent group, and five eyes (five cases) were in the chronic group. Two eyes (two cases) had abnormalities on OCT in the pretreatment and recurrent or chronic stages. The pretreatment and recurrent groups had subretinal or retinal pigment epithelium (RPE) level abnormalities more often than intraretinal changes. Twelve of 16 pretreated eyes and all seven eyes with recurrent disease had subretinal or RPE level abnormalities. One pretreatment case and three recurrent cases had atypical OCT manifestations of intraretinal (round lesions) or epiretinal changes (villous shaped lesions). CONCLUSIONS: Although pretreatment cases and recurrent cases showed similar OCT abnormalities and the specific changes in the various disease stages were unclarified, collecting OCT data from various disease stages will facilitate detection of typical OCT changes of PVRL and lead to early diagnosis and treatment. PMID- 27251193 TI - Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration. PMID- 27251194 TI - A novel blue light laser system for surgical applications in dentistry: evaluation of specific laser-tissue interactions in monolayer cultures. AB - OBJECTIVES: The objective of this study was to examine a new blue light diode laser system (445 nm) for dental soft tissue surgery on cellular level. MATERIALS AND METHODS: An in vitro cell culture model was established to evaluate the effects of the 445-nm diode laser in comparison to an established infrared diode laser (IR). Monolayer cell cultures were irradiated and wound healing was morphometrically measured. Fluorescence staining was used for proof of potential DNA double-strand breaks as well as cytoskeleton alterations. Cellular live/dead discrimination was performed and temperature development during laser irradiation was measured with a thermographic infrared camera. RESULTS: A characteristic zone formation was detected after irradiation with both wavelengths. Despite a larger wound area after irradiation with 445 nm, due to its higher temperature development, this laser system showed a faster wound healing in comparison to the IR laser. No increase of devitalized cells was documented with higher distances between laser tip and cell layer and thus without thermal interaction. Neither cytoskeleton alteration nor DNA double-strand breaks could be recorded after irradiation in non-contact mode. CONCLUSIONS: The blue diode laser system demonstrated an excellent direct thermal coupling to cells and tissues without side effects even by reduced power settings. CLINICAL RELEVANCE: The blue diode laser seems to be a promising technology for clinical application due to high absorption of blue light without major side effects in adjacent tissues even by reduced power settings. PMID- 27251195 TI - Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator. AB - The precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain. Unilateral intra-plantar supplementation of proBDNF by injecting exogenous proBDNF or ectopic overexpression resulted in pain hypersensitivity and induced spinal phosphorylated extracellular signal-regulated kinase activation. Exogenous proBDNF injection induced the infiltration of inflammatory cells and the activation of proinflammatory cytokines, suggesting that inflammatory reaction contributed to the pro-algesic effect of proBDNF. Finally, we generated monoclonal anti-proBDNF antibody that could biologically block proBDNF. Administration of monoclonal Ab-proBDNF attenuated various types of inflammatory pain and surgical pain. Thus, peripheral proBDNF is a potential pain mediator and anti-proBDNF pretreatment may alleviate the development of inflammatory pain. PMID- 27251196 TI - Comparison of cell counting methods in rodent pulmonary toxicity studies: automated and manual protocols and considerations for experimental design. AB - Pulmonary toxicity studies often use bronchoalveolar lavage (BAL) to investigate potential adverse lung responses to a particulate exposure. The BAL cellular fraction is counted, using automated (i.e. Coulter Counter(r)), flow cytometry or manual (i.e. hemocytometer) methods, to determine inflammatory cell influx. The goal of the study was to compare the different counting methods to determine which is optimal for examining BAL cell influx after exposure by inhalation or intratracheal instillation (ITI) to different particles with varying inherent pulmonary toxicities in both rat and mouse models. General findings indicate that total BAL cell counts using the automated and manual methods tended to agree after inhalation or ITI exposure to particle samples that are relatively nontoxic or at later time points after exposure to a pneumotoxic particle when the response resolves. However, when the initial lung inflammation and cytotoxicity was high after exposure to a pneumotoxic particle, significant differences were observed when comparing cell counts from the automated, flow cytometry and manual methods. When using total BAL cell count for differential calculations from the automated method, depending on the cell diameter size range cutoff, the data suggest that the number of lung polymorphonuclear leukocytes (PMN) varies. Importantly, the automated counts, regardless of the size cutoff, still indicated a greater number of total lung PMN when compared with the manual method, which agreed more closely with flow cytometry. The results suggest that either the manual method or flow cytometry would be better suited for BAL studies where cytotoxicity is an unknown variable. PMID- 27251197 TI - Experimental and computational studies on molecularly imprinted solid-phase extraction for gonyautoxins 2,3 from dinoflagellate Alexandrium minutum. AB - An innovative and effective extraction procedure based on molecularly imprinted solid-phase extraction (MISPE) was developed for the isolation of gonyautoxins 2,3 (GTX2,3) from Alexandrium minutum sample. Molecularly imprinted polymer microspheres were prepared by suspension polymerization and and were employed as sorbents for the solid-phase extraction of GTX2,3. An off-line MISPE protocol was optimized. Subsequently, the extract samples from A. minutum were analyzed. The results showed that the interference matrices in the extract were obviously cleaned up by MISPE procedures. This outcome enabled the direct extraction of GTX2,3 in A. minutum samples with extraction efficiency as high as 83 %, rather significantly, without any need for a cleanup step prior to the extraction. Furthermore, computational approach also provided direct evidences of the high selective isolation of GTX2,3 from the microalgal extracts. PMID- 27251198 TI - Screen-printed electrode modified with carbon black and chitosan: a novel platform for acetylcholinesterase biosensor development. AB - We report a screen-printed electrode (SPE) modified with a dispersion of carbon black (CB) and chitosan by drop casting. A cyclic voltammetry technique towards ferricyanide, caffeic acid, hydroquinone, and thiocholine was performed and an improvement of the electrochemical response with respect to bare SPE as well as SPE modified only with chitosan was observed. The possibility to detect thiocholine at a low applied potential with high sensitivity was exploited and an acetylcholinesterase (AChE) biosensor was developed. A dispersion of CB, chitosan, and AChE was used to fabricate this biosensor in one step by drop casting. The enzymatic activity of the immobilized AChE was determined measuring the enzymatic product thiocholine at +300 mV. Owing to the capability of organophosphorus pesticides to inhibit AChE, this biosensor was used to detect these pollutants, and paraoxon was taken as model compound. The enzyme inhibition was linearly related to the concentration of paraoxon up to 0.5 MUg L(-1), and a low detection limit equal to 0.05 MUg L(-1) (calculated as 10% of inhibition) was achieved. This biosensor was challenged for paraoxon detection in drinking waters with satisfactory recovery values. The use of AChE embedded in a dispersion of CB and chitosan allowed an easy and fast production of a sensitive biosensor suitable for paraoxon detection in drinking waters at legal limit levels. Graphical Abstract Biosensors based on screen-printed electrodes modified with Acetylcholinesterase, Carbon Black, and Chitosan for organophosphorus pesticide detection. PMID- 27251200 TI - Risk based survey evidence supports electronic informed consent as a recruitment method for UK clinical trials. PMID- 27251201 TI - Transport spectroscopy on trapped superconducting nano-islands of Pb: signature of unconventional pairing. AB - Elemental bulk lead (Pb) is a conventional type I, spin-singlet (s-wave) superconductor with a critical temperature T c = 7.2 K and a critical magnetic field H c = 800 Oe. However, it is known that at mesoscopic length scales, like in point-contact geometries, Pb shows significantly higher critical field, sometimes up to several Tesla. We have used this property to trap a small superconducting nano-droplet of Pb by forming a metallic point contact on Pb and then applying a magnetic field larger than 800 Oe that drives the bulk of the material non-superconducting. From systematic magnetic field dependent behaviour of the point-contact spectra measured across such a trapped island of Pb we show that the superconducting order parameter of mesoscopic Pb mixes non-trivially with magnetic field possibly due to the emergence of a local spin-triplet component at such length scales. From comparative studies with Nb-based point contacts we surmise that the strong spin-orbit coupling in Pb leads to the emergence of the unconventional component in the order parameter of mesoscopic Pb. PMID- 27251199 TI - Combating poor-quality anti-malarial medicines: a call to action. AB - The circulation of poor-quality medicines continues to undermine the fight against many life-threatening diseases. Anti-malarial medicines appear to have been particularly compromised and present a major public health threat in malaria endemic countries, negatively affecting individuals and their communities. Concerted collaborative efforts are required from global, regional and national organizations, involving the public and private sectors, to address the problem. While many initiatives are underway, a number of unmet needs deserve urgent and increased multisector attention. At the global level, there is a need for an international public health legal framework or treaty on poor-quality medicines, with statutes suitable for integration into national laws. In addition, increased international efforts are required to strengthen the governance of global supply chains and enhance cooperation between national medicine regulation authorities and law enforcement bodies. Increased investment is needed in innovative technologies that will enable healthcare teams to detect poor-quality medicines at all levels of the supply chain. At the regional level, a number of initiatives would be beneficial-key areas are standardization, simplification, and reciprocal recognition of registration processes and development of quality control capacity in regional centres of excellence that are better aligned with public health needs; improved surveillance methods and creation of a framework for compulsory and transparent reporting of poor-quality medicines; additional support for national medicine regulation authorities and other national partner authorities; and an increase in support for regional laboratories to boost their capabilities in detecting poor-quality medicines. It is vital that all stakeholders involved in efforts against poor-quality anti-malarial medicines extend and strengthen their actions in these critical areas and thus effectively support global health development and malaria elimination programmes. PMID- 27251202 TI - Impact of vitrification on the mitochondrial activity and redox homeostasis of human oocyte. AB - STUDY QUESTION: Do the extreme conditions of vitrification affect mitochondrial health and reactive oxygen species (ROS) levels of human oocytes? SUMMARY ANSWER: Vitrification of discarded human oocytes shifts the intracellular redox potential towards oxidation but does not alter the mitochondrial potential or intracellular ROS levels. WHAT IS KNOWN ALREADY: Recent studies have reflected increased ROS levels in warmed young oocytes and have highlighted the temporal dynamic loss of mitochondrial potential that could, therefore, lead to a decrease in ATP production, impairing embryo development. Mitochondrial function can also be evaluated in vivo by the FAD/NAD(P)H autofluorescence ratio, which reflects the respiratory chain activity and is considered as a marker of the intracellular redox state. STUDY DESIGN, SIZE, DURATION: A total of 629 discarded Metaphase II (MII) oocytes collected from June 2013 to April 2014 were included in this control (fresh oocytes, n= 270) versus treatment (vitrified oocytes, n= 359) study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Discarded MII oocytes were donated to research by young (<27 years old) and reproductively aged (>36 years old) women who underwent ovarian stimulation for IVF at a university-affiliated private fertility clinic. Redox state was assessed by measuring the FAD/NAD(P)H autofluorescence ratio, while ROS and mitochondrial activity were reported by in vivo labelling with carboxy-H2DCFDA and JC-1, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Young and aged oocytes showed high and similar survival rates (81.8 versus 83.1%, not significant). Confocal microscopy revealed that the FAD/NAD(P)H ratio was significantly higher in vitrified oocytes than in fresh oocytes, suggesting a significant shift towards the oxidized state in oocytes after vitrification, regardless of the maternal age. Mitochondrial distribution was not affected by vitrification. Furthermore, it was not possible to resolve any difference in mitochondrial potential using JC-1 potentiometric dye or in reactive oxygen species (ROS) production (assessed with H2-DCFDA staining) between fresh and vitrified oocytes. Therefore, measurement of intracellular redox potential by autofluorescence imaging may be a more sensitive method to assess oxidative stress or mitochondrial demise in human oocytes because it showed a higher resolving power than JC-1 staining and displayed less variability than H2-DCFDA staining. LIMITATIONS, REASONS FOR CAUTION: Owing to sample availability, MII discarded oocytes (in vitro matured oocytes and unfertilized oocytes 20 h after ICSI) were included in the study. These discarded oocytes do not necessarily reflect the physiological condition of the MII human oocyte. WIDER IMPLICATIONS OF THE FINDINGS: Although vitrified oocytes yield comparable clinical outcomes compared with fresh oocytes, lower cleavage and blastocyst rates can be observed during in vitro culture. Data here obtained suggest that the redox state of human oocytes could be affected by vitrification. Therefore, the importance of adding protective antioxidant molecules to the vitrification solution and to the post-warming culture medium to improve embryo cleavage deserves some research. STUDY FUNDING/COMPETING INTERESTS: This research project was supported by the Valencian Government (Val+i+D program, M.N.-C.), INCLIVA Foundation for health research (G.S.-A.) and by the University of L'Aquila and Regione Abruzzo ('Reti per l'Alta Formazione' - P.O.F.S.E. Abruzzo 2007-2013 G.D.E.). No conflicts of interest were declared. PMID- 27251204 TI - Trends and determinants of IUD use in the USA, 2002-2012. AB - STUDY QUESTION: What factors and subgroups have propelled the recent increase in intrauterine device (IUD) use in the USA? SUMMARY ANSWER: The increase in IUD use, from 1.8 to 9.5% in the USA between 2002 and 2012, was driven primarily by a marked uptake among parous women who intended to have more children. WHAT IS KNOWN ALREADY: Recent data suggest an unprecedented increase in IUD use among women in the USA, yet less is known about how this increase has affected the overall proportion of women, at risk of unintended pregnancy, who are using contraception and which social and economic groups are involved. STUDY DESIGN, SIZE, DURATION: Data are drawn from the 2002 and 2011-2013 National Surveys of Family Growth. The surveys were based on cross-sectional, national samples of women of 15-44 years of age in the USA. Women responded to in-person interviews, which lasted an average of 80 min. The response rate was 80% in 2002 and 73% in 2011-2013. The sample included 7643 completed interviews in 2002 and 5601 interviews in 2011-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was limited to women at risk of unintended pregnancy, i.e. women who were sexually active in the previous 3 months (using contraception or not); it excludes women who were sterile, currently pregnant or trying to conceive. Altogether, 5181 women were at risk in the 2002 sample and 3681 were at risk in the 2012 sample. We used descriptive statistics to investigate trends in contraceptive use patterns by women's sociodemographic characteristics between 2002 and 2012 and used logistic regression to identify current predictors of IUD use in 2012. MAIN RESULTS AND THE ROLE OF CHANCE: IUD use increased from 1.8% in 2002 to 9.5% in 2012 (P < 0.001). The surge was especially marked among parous women who intended to have more children (4.2% in 2002 to 19.3% in 2012; P < 0.001); it occurred to a lesser extent among parous women who did not intend to have more children (2.0 9.7% P < 0.001), suggesting that IUDs are more often used for spacing than for ending childbearing in the USA. The most important predictors of IUD use in 2012 were age, parity and intent to have children. Dissatisfaction with a previous method was also associated with IUD use (adjusted odds ratio = 1.89, P < 0.001). LIMITATIONS, REASONS FOR CAUTION: As with all cross-sectional studies, causal inference is limited. Data are self-reported, but the survey had a high response rate and rigorous quality controls. WIDER IMPLICATION OF THE FINDINGS: This study shows promising trends in the use of highly effective contraceptive methods in the USA, which may help to explain recently reported declines in unintended pregnancy in the USA. STUDY FUNDING/COMPETING INTERESTS: Caroline Moreau was supported by the William Robertson endowment funds. The work of Hannah Lantos and William Mosher on this analysis was supported by the Department of Population Family and Reproductive Health, The Johns Hopkins Bloomberg School of Public Health. The authors declare that no conflict of interest exists. PMID- 27251203 TI - Charged iron particles, components of space radiation, destroy ovarian follicles. AB - STUDY QUESTION: Do charged iron particles, components of space radiation, cause premature ovarian failure? SUMMARY ANSWER: Exposure to charged iron particles causes ovarian DNA damage, oxidative damage and apoptosis, resulting in premature ovarian failure. WHAT IS KNOWN ALREADY: The ovary is very sensitive to follicle destruction by low linear energy transfer (LET) radiation, such as X-rays and gamma-rays. However, it is completely unknown whether high-LET radiation, such as charged iron particles, also destroys ovarian follicles. STUDY DESIGN, SIZE, DURATION: Twelve week old C57BL/6J female mice were exposed to single doses of 0, 5, 30 or 50 cGy (n = 8/group) charged iron particles (LET = 179 keV/um) at energy of 600 MeV/u. Two groups were irradiated at the highest dose, one fed AIN-93M chow and the other fed AIN-93M chow supplemented with 150 mg/kg diet alpha lipoic acid (ALA). PARTICIPANTS/MATERIALS, SETTING, METHODS: We quantified the numbers of ovarian follicles, measured serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations, and analyzed histone H2AX phosphorylation, oxidative damage and apoptosis markers in the ovarian follicles. MAIN RESULTS AND THE ROLE OF CHANCE: H2AX phosphorylation, lipid peroxidation, protein nitration and apoptosis were highly induced in ovarian follicles at 6 h and remained increased 1 week after irradiation. As a result, numbers of healthy ovarian follicles were significantly and dose-dependently depleted at 1 and 8 weeks post-irradiation, with 57, 84 and 99% decreases in primordial follicles at 8 weeks at the 5, 30 and 50 cGy doses, respectively (P < 0.05 versus 0 cGy). Consistent with near-total depletion of ovarian follicles in the 50 cGy group, serum concentrations of FSH and LH were significantly elevated at 8 weeks. Dietary supplementation with ALA partially prevented the adverse ovarian effects of 50 cGy iron particles. LIMITATIONS, REASONS FOR CAUTION: About 21% of the estimated radiation dose from exposure to galactic cosmic rays during a multi year Mars mission will be due to high-LET particles, of which iron is only one. The effects of galactic cosmic rays, which contain a mixture of multiple charged particles, as well as protons, neutrons, and helium ions, may differ from the effects of iron alone. WIDER IMPLICATIONS OF THE FINDINGS: We show for the first time that charged high-LET ions are highly damaging to the ovary even at low doses, causing premature ovarian failure. In addition to raising concerns for female astronauts, these findings raise concerns for ovarian damage due to clinical uses of high-LET particles for cancer treatment. In addition to causing infertility, premature ovarian failure has adverse implications for the functions of heart, brain, bone and muscle later in life. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a National Aeronautics and Space Administration grant NNX14AC50G to U.L. B.M. was partially supported by a National Space Biomedical Research Institute First Award, PF04302. Additional support was received from the University of California Irvine Center for Occupational and Environmental Health. The authors have no conflicts of interests. PMID- 27251205 TI - Hospital admission for hyperemesis gravidarum: a nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies. AB - STUDY QUESTION: What are the maternal risk factors for hyperemesis gravidarum (HG) hospital admission, readmission and reoccurrence in a following pregnancy? SUMMARY ANSWER: Young age, less socioeconomic deprivation, nulliparity, Asian or Black ethnicity, female fetus, multiple pregnancy, history of HG in a previous pregnancy, thyroid and parathyroid dysfunction, hypercholesterolemia and Type 1 diabetes are all risk factors for HG. WHAT IS KNOWN ALREADY: Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with a history of HG were previously reported to be at higher risk of developing HG; however, most evidence is from small studies. Little is known about associations with other comorbidities and there is controversy over other risk factors such as parity. Estimates of HG prevalence vary and there is a little understanding of the risks of HG readmission in a current pregnancy and reoccurrence rates in subsequent pregnancies, all of which are needed for planning measures to reduce onset or worsening of the condition. STUDY DESIGN, SIZE, DURATION: We performed a population-based cohort study of pregnancies ending in live births and stillbirths using prospectively recorded secondary care records (Hospital Episode Statistics) from England. We analysed those computerized and anonymized clinical records from over 5.3 million women who had one or more pregnancies between 1997 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained 8 215 538 pregnancies from 5 329 101 women of reproductive age, with a total of 186 800 HG admissions occurring during 121 885 pregnancies. Multivariate logistic regression with generalized estimating equations was employed to estimate odds ratios (aOR) to assess sociodemographic, pregnancy and comorbidity risk factors for HG onset, HG readmission within a pregnancy and reoccurrence in a subsequent pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Being younger, from a less socioeconomically deprived status, of Asian or Black ethnicity, carrying a female fetus or having a multiple pregnancy all significantly increased HG and readmission risk but only ethnicity increased reoccurrence. Comorbidities most strongly associated with HG were parathyroid dysfunction (aOR = 3.83, 95% confidence interval 2.28-6.44), hypercholesterolemia (aOR = 2.54, 1.88-3.44), Type 1 diabetes (aOR = 1.95, 1.82-2.09), and thyroid dysfunction (aOR = 1.85, 1.74-1.96). History of HG was the strongest independent risk factor (aOR = 4.74, 4.46-5.05). Women with higher parity had a lower risk of HG compared with nulliparous women (aOR = 0.90, 0.89-0.91), which was not explained by women with HG curtailing further pregnancies. LIMITATIONS, REASONS FOR CAUTION: Although this represents the largest population-based study worldwide on the topic, the results could have been biased by residual and unmeasured confounding considering that some potential important risk factors such as smoking, BMI or prenatal care could not be measured with these data. Underestimation of non-routinely screened comorbidities such as hypercholesterolemia or thyroid dysfunction could also be a cause of selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The estimated prevalence of 1.5% from our study was similar to the average prevalence reported in the literature and the representativeness of our data has been validated by comparison to national statistics. Also the prevalence of comorbidities was mostly similar to other studies estimating these in the UK and other developed countries. Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with history of HG were confirmed to be at higher risk of HG with an unprecedented higher statistical power. We showed for the first time that socioeconomic status interacts with maternal age, that hypercholesterolemia is a potential risk factor for HG and that carrying multiple females increases risk of hyperemesis compared with multiple males. We also provided robust evidence for the association of parity with HG. Earlier recognition and management of symptoms via gynaecology day-case units or general practitioner services can inform prevention and control of consequent hospital admissions. STUDY FUNDING/COMPETING INTERESTS: The work was founded by The Rosetrees Trust and the Stoneygate Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.N.-P. reports personal fees from Sanofi Aventis, Warner Chilcott, Leo Pharma, UCB and Falk, outside the submitted work and she is one of the co developers of the RCOG Green Top Guideline on HG; all other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable. PMID- 27251206 TI - Therapy: HCV drugs reduce transplantation need. PMID- 27251207 TI - IBD: Sensing gene-microbiota signals in IBD. PMID- 27251208 TI - Paediatrics: Diagnostic yield of paediatric lower gastrointestinal endoscopy. PMID- 27251209 TI - Paediatrics: Fruitful therapy for dehydration. PMID- 27251210 TI - IBD: Exposure to anti-TNF agents in utero: controlling health risks. PMID- 27251211 TI - Liver cancer: A new drug target for hepatocellular carcinoma. PMID- 27251212 TI - Therapy: Colorectal cancer: how to teach an old drug new tricks. PMID- 27251214 TI - Gastrointestinal cancer: Neutrophils and cancer: guilt by association. PMID- 27251215 TI - Catch-up growth and growth deficits: Nine-year annual panel child growth for native Amazonians in Bolivia. AB - BACKGROUND: Childhood growth stunting is negatively associated with cognitive and health outcomes, and is claimed to be irreversible after age 2. AIM: To estimate growth rates for children aged 2-7 who were stunted (sex-age standardised z-score [HAZ] <-2), marginally-stunted (-2 <= HAZ <=-1) or not-stunted (HAZ >-1) at baseline and tracked annually until age 11; frequency of movement among height categories; and variation in height predicted by early childhood height. SUBJECTS AND METHODS: This study used a 9-year annual panel (2002-2010) from a native Amazonian society of horticulturalists-foragers (Tsimane'; n = 174 girls; 179 boys at baseline). Descriptive statistics and random-effect regressions were used. RESULTS: This study found some evidence of catch-up growth in HAZ, but persistent height deficits. Children stunted at baseline improved 1 HAZ unit by age 11 and had higher annual growth rates than non-stunted children. Marginally stunted boys had a 0.1 HAZ units higher annual growth rate than non-stunted boys. Despite some catch up, ~ 80% of marginally-stunted children at baseline remained marginally-stunted by age 11. The height deficit increased from age 2 to 11. Modest year-to-year movement was found between height categories. CONCLUSIONS: The prevalence of growth faltering among the Tsimane' has declined, but hurdles still substantially lock children into height categories. PMID- 27251216 TI - Perioperative complications of scoliosis surgery in patients with Duchenne muscular dystrophy and spinal muscular atrophy, focussing on wound healing disorders. AB - PURPOSE: Patients with Duchenne muscular dystrophy (DMD) or spinal muscular atrophy (SMA), both neuromuscular diseases, sustain spinal scoliosis in the course of their disease. To reduce the concomitant major morbidity and to improve their quality of life, patients require surgical spine stabilization. This can lead to complications like respiratory, cardiac or neurological complications or wound healing disorders (WHD). To find out the different complexities and risk factors increasing the chance to develop a WHD, the inpatient database was analyzed. METHODS: We performed a retrospective statistical study. Therefore, we analyzed the inpatient database of 180 patients (142 DMD and 38 SMA patients). The focus was on WHD. To figure out the risk factors leading to WHD, we conducted a logistic regression. RESULTS: Cardiac complications occurred most frequently, followed by pulmonary complications and neurological lesions. Fifty-seven out of 180 patients developed a WHD. In 23 cases the WHD was aseptic, in the other 34 cases dermal organisms, Pseudomonas species and intestinal organisms were responsible. By means of the logistic regression, we were able to identify two more risk factors, in addition to diagnosis and gender, for developing a WHD in our patients: the year of surgery and the direction of pelvic tilt. CONCLUSIONS: Most common complications following scoliosis surgery are respiratory and cardiac complications. WHD is a severe complication that implies a prolonged therapy. Some risk factors for developing WHD could be identified in this analysis. Specifically, these were the date of surgery and the direction of pelvic tilt. PMID- 27251213 TI - Vagal neurocircuitry and its influence on gastric motility. AB - A large body of research has been dedicated to the effects of gastrointestinal peptides on vagal afferent fibres, yet multiple lines of evidence indicate that gastrointestinal peptides also modulate brainstem vagal neurocircuitry, and that this modulation has a fundamental role in the physiology and pathophysiology of the upper gastrointestinal tract. In fact, brainstem vagovagal neurocircuits comprise highly plastic neurons and synapses connecting afferent vagal fibres, second order neurons of the nucleus tractus solitarius (NTS), and efferent fibres originating in the dorsal motor nucleus of the vagus (DMV). Neuronal communication between the NTS and DMV is regulated by the presence of a variety of inputs, both from within the brainstem itself as well as from higher centres, which utilize an array of neurotransmitters and neuromodulators. Because of the circumventricular nature of these brainstem areas, circulating hormones can also modulate the vagal output to the upper gastrointestinal tract. This Review summarizes the organization and function of vagovagal reflex control of the upper gastrointestinal tract, presents data on the plasticity within these neurocircuits after stress, and discusses the gastrointestinal dysfunctions observed in Parkinson disease as examples of physiological adjustment and maladaptation of these reflexes. PMID- 27251217 TI - The risk-outcome-experience triad: Mortality risk and the hospital consumer assessment of healthcare providers and systems survey. AB - BACKGROUND: Studies have shown an association between the Hospital Consumer Assessment of Healthcare Providers and Systems Survey (HCAHPS) scores and clinical quality. The mortality risk on admission predicts adverse events. It is not known if this risk also portends a suboptimal patient experience. OBJECTIVE: To determine if the admission mortality risk identifies an experience of care risk. DESIGN: A retrospectively assembled cohort in which individual HCAHPS survey responses were linked to the admission risk of dying. SETTING: Five community hospitals of various sizes in Michigan. PATIENTS: There were 17,509 HCAHPS medical and surgical respondents; 2513 (14.4%) were at high risk of dying. MEASUREMENTS: Odds ratio (OR) (high-risk patients to low-risk patients) for providing a top box score for HCAHPS dimensions, controlling for hospital and the standard HCAHPS patient mix adjustment factors. RESULTS: High-risk respondents were less likely to provide the most favorable response (unadjusted) for all HCAHPS domains, although the difference was not significant (P = 0.09) for discharge information. Multivariable analyses indicated that high-risk patients were less likely to report a top box experience for doctor communication (OR: 0.85; 95% confidence interval [CI]: 0.77-0.94) and responsiveness of hospital staff (OR: 0.77; 95% CI: 0.69-0.85), but were more likely to have received adequate discharge information (OR: 1.30, 95% CI: 1.14-1.48). CONCLUSIONS: Patients at high risk of dying who completed surveys were less likely to report favorable physician communication and staff responsiveness. Further understanding of these relationships may help design a care model to improve both outcomes and experience. Journal of Hospital Medicine 2016;11:628-635. (c) 2016 Society of Hospital Medicine. PMID- 27251219 TI - Monitoring Natural World Heritage Sites: optimization of the monitoring system in Bogda with GIS-based multi-criteria decision analysis. AB - Natural World Heritage Sites (NWHSs) are invaluable treasure due to the uniqueness of each site. Proper monitoring and management can guarantee their protection from multiple threats. In this study, geographic information system (GIS)-based multi-criteria decision analysis (GIS-MCDA) was used to assess criteria layers acquired from the data available in the literature. A conceptual model for determining the priority area for monitoring in Bogda, China, was created based on outstanding universal values (OUV) and expert knowledge. Weights were assigned to each layer using the analytic hierarchy process (AHP) based on group decisions, encompassing three experts: one being a heritage site expert, another a forest ranger, and the other a heritage site manager. Subsequently, evaluation layers and constraint layers were used to generate a priority map and to determine the feasibility of monitoring in Bogda. Finally, a monitoring suitability map of Bogda was obtained by referencing priority and feasibility maps.The high-priority monitoring area is located in the montane forest belt, which exhibits high biodiversity and is the main tourist area of Bogda. The northern buffer zone of Bogda comprises the concentrated feasible monitoring areas, and the area closest to roads and monitoring facilities is highly feasible for NWHS monitoring. The suitability of an area in terms of monitoring is largely determined by the monitoring priority in that particular area. The majority of planned monitoring facilities are well distributed in both suitable and less suitable areas. Analysis results indicate that the protection of Bogda will be more scientifically based due to its effective and all-around planned monitoring system proposed by the declaration text of Xinjiang Tianshan, which is the essential file submitted to World Heritage Centre to inscribe as a NWHS. PMID- 27251218 TI - Construction and immunogenicity of a new Fc-based subunit vaccine candidate against Mycobacterium tuberculosis. AB - As an ancient disease, tuberculosis (TB) is a major global health threat. Therefore, there is an urgent need for an effective and safe anti-TB vaccine. In the current study, a delivery system of Fc domain of mouse IgG2a and early secreted antigenic target protein 6 (ESAT-6) was evaluated for the selective uptake of antigens by antigen-presenting cells (APCs). Thus, it was based on the immunogenicity of a fusion protein. The study was initiated by the transfer of recombinant expression vectors of pPICZalphaA-ESAT-6:Fcgamma2a and pPICZalphaA ESAT-6: His into Pichia pastoris (P. pastoris). Recombinant proteins were assessed for immunogenicity following the immunoblotting analysis. High levels of IFN-gamma and IL-12 were produced to induce Th1-type cellular responses through vaccination with both recombinant proteins [ESAT-6:Fcgamma2a (EF) and ESAT-6:His (EH)]. The Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a low increment in IL-4 compared to PBS, BCG, and EH groups. Although in all the immunized groups, the ratio of IFN-gamma/IL-4 was in favor of Th1 responses, the highest Th1/Th2 balance was observed in EF immunized group. Fc fragment of mouse IgG2a may induce a selective uptake of APCs towards the cross presentation and formation of Th1 responses in favor of an appropriate protective anti-tuberculosis reaction. Thus, further research on Fc-fusion proteins is required to develop Fc-based TB vaccines. PMID- 27251220 TI - Current status of seawater quality in Digha (India), northwestern coast of the Bay of Bengal. AB - The present investigation was intended to assess the seawater quality of Digha (India) in the northwestern coast of the Bay of Bengal. Digha is a meso-tidal coastal plain located between two major estuarine systems, i.e. Subarnarekha and Hooghly located respectively on the western and eastern sides of the West Bengal along the northeast coast of India. The sampling was made at nine stations at various distances. Significant seasonal variations in environmental parameters and nutrients were observed during the study period. Analyses of physicochemical characteristics of the study area indicated that the level of dissolved oxygen (DO), biological oxygen demand (BOD), total dissolved solid (TDS) and nutrients is within the permissible limit. The results clearly revealed that, though sewage discharge takes place in the coastal waters, the quality of the water was not affected. It may be due to the large quantity of estuarine water input from the Hooghly estuarine system that have enhanced dilution of discharged sewage in Digha coastal waters. Strong tidal activities, wave dynamics and coastal current further dilute the effluent water in the study area, resulting to the minimised sewage effect on coastal ecosystem. Further studies on the heavy metal concentration and benthic diversity can be assessed to understand the health of the ecosystem. PMID- 27251221 TI - Occurrence and estimation of pesticide residues in edible minor crops in southeastern Poland in 2013-2014. AB - This paper presents the results of official control of pesticide residues in minor crops collected in southeastern Poland in 2013-2014. Compliance of used pesticides with applicable law was also verified, and determined residues were compared to maximum residue levels (MRLs) provided for in Regulation (EC) No. 395/2005. A total of 583 samples of 25 different types of fresh fruit and vegetables were analyzed for pesticide residues. Pesticide residues were detected in 158 samples (27.1 % of the analyzed samples). According to the European Commission Health & Consumer Protection Directorate-General (SANCO) guidelines document, MRL violations were understood as cases where a residue level exceeded the MRL after the uncertainty of the method (50 %) was considered. MRL violations were found in four samples. The usage of unauthorized pesticides was detected in 5.8 % of analyzed samples. Substances banned in Poland were found in two samples. Fungicides were the most frequently detected group of pesticides. Pesticide residues were most commonly found in fruit samples (19.4 % of all analyzed samples), mainly in gooseberry, redcurrant, and huckleberry. The majority of samples were compliant with MRLs, which means that they were suitable for trade. PMID- 27251222 TI - Biohydrogen Production from Hydrolysates of Selected Tropical Biomass Wastes with Clostridium Butyricum. AB - Biohydrogen production has received widespread attention from researchers in industry and academic fields. Response surface methodology (RSM) was applied to evaluate the effects of several key variables in anaerobic fermentation of glucose with Clostridium butyrium, and achieved the highest production rate and yield of hydrogen. Highest H2 yield of 2.02 mol H2/mol-glucose was achieved from 24 h bottle fermentation of glucose at 35 degrees C, while the composition of medium was (g/L): 15.66 glucose, 6.04 yeast extract, 4 tryptone, 3 K2HPO4, 3 KH2PO4, 0.05 L-cysteine, 0.05 MgSO4.7H2O, 0.1 MnSO4.H2O and 0.3 FeSO4.7H2O, which was very different from that for cell growth. Sugarcane bagasse and Jatropha hulls were selected as typical tropical biomass wastes to produce sugars via a two-step acid hydrolysis for hydrogen production. Under the optimized fermentation conditions, H2 yield (mol H2/mol-total reducing sugar) was 2.15 for glucose, 2.06 for bagasse hydrolysate and 1.95 for Jatropha hull hydrolysate in a 3L fermenter for 24 h at 35 degrees C, with H2 purity of 49.7-64.34%. The results provide useful information and basic data for practical use of tropical plant wastes to produce hydrogen. PMID- 27251224 TI - Anomalous mitral and tricuspid arcade in a patient with stenotic double-orifice tricuspid valve. PMID- 27251223 TI - Evidence for participation of neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9 (NGAL*MMP-9) complex in the inflammatory response to infection in pregnancies complicated by preterm birth. AB - PROBLEM: Neutrophil gelatinase-associated lipocalin (NGAL) is expressed in neutrophils and involved in innate immunity by sequestering iron. NGAL's ability to complex with matrix metalloproteinase-9 (MMP-9) and extend its gelatinolytic activity led us to investigate its role in pregnancies complicated by preterm birth (PTB) and intra-amniotic infection/inflammation (IAI). METHOD OF STUDY: We assayed the amniotic fluid (AF) levels of NGAL and MMP-9 in 308 women that had a clinically indicated amniocentesis and a normal pregnancy outcome or PTB. qRT-PCR was employed to determine NGAL mRNA expression of placental villous trophoblast and amniochorion. Immunohistochemistry was used for cellular localization. RESULTS: AF NGAL levels were gestational age-regulated. Women with IAI and PTB had significantly higher levels of NGAL, MMP-9 and NGAL*MMP-9 complex. CONCLUSION: The amniochorion is a source of NGAL and similarly to other inflammatory conditions, this protein may augment the collagenolytic effect of MMP-9 and modulate host-microbe interactions in pregnancies complicated by IAI. PMID- 27251226 TI - Norm statement considered harmful: comment on 'evolution of unconditional dispersal in periodic environments'. AB - The mathematical symbol for the norm, which is heavily overloaded with multiple definitions that have both universal and specific properties, lends itself to confusion. This is manifest in the proof of an important theorem for population dynamics by Schreiber and Li on how dispersal increases population growth in a periodic environment. Here the theorem is placed in context, the proof is clarified, and the confusing but inconsequential errors corrected. PMID- 27251225 TI - RANKL expression is a useful marker for differentiation of pagetoid squamous cell carcinoma in situ from extramammary Paget disease. AB - BACKGROUND: Pagetoid squamous cell carcinoma in situ (SCCIS) is a histopathologic variant of SCCIS composed of cells that display an abundant, pale-staining cytoplasm in a pagetoid distribution within the epidermis. As pagetoid SCCIS is sometimes difficult to differentiate from extramammary Paget disease (EMPD) histopathologically, specific markers for pagetoid SCCIS or EMPD are needed by dermatopathologists. METHODS: In this report, we employed immunohistochemical staining for receptor of activated nuclear factor kappa ligand (RANKL) and programmed death-ligand 1 (PD-L1) in six cases each of pagetoid SCCIS and EMPD. RESULTS: The Paget cells strongly expressed RANKL in EMPD, whereas the atypical keratinocytes did not express RANKL in any of the six cases of pagetoid SCCIS. In all cases of pagetoid SCCIS, atypical keratinocytes expressed PD-L1. In EMPD, Paget cells expressed PD-L1 in half of the cases at a lower level of expression than was seen in the surrounding keratinocytes. CONCLUSION: This study suggested that RANKL, but not PD-L1, could be a marker to differentiate between pagetoid SCCIS and EMPD. PMID- 27251227 TI - Trichocysts-Paramecium's Projectile-like Secretory Organelles: Reappraisal of their Biogenesis, Composition, Intracellular Transport, and Possible Functions. AB - This review summarizes biogenesis, composition, intracellular transport, and possible functions of trichocysts. Trichocyst release by Paramecium is the fastest dense core-secretory vesicle exocytosis known. This is enabled by the crystalline nature of the trichocyst "body" whose matrix proteins (tmp), upon contact with extracellular Ca2+ , undergo explosive recrystallization that propagates cooperatively throughout the organelle. Membrane fusion during stimulated trichocyst exocytosis involves Ca2+ mobilization from alveolar sacs and tightly coupled store-operated Ca2+ -influx, initiated by activation of ryanodine receptor-like Ca2+ -release channels. Particularly, aminoethyldextran perfectly mimics a physiological function of trichocysts, i.e. defense against predators, by vigorous, local trichocyst discharge. The tmp's contained in the main "body" of a trichocyst are arranged in a defined pattern, resulting in crossstriation, whose period expands upon expulsion. The second part of a trichocyst, the "tip", contains secretory lectins which diffuse upon discharge. Repulsion from predators may not be the only function of trichocysts. We consider ciliary reversal accompanying stimulated trichocyst exocytosis (also in mutants devoid of depolarization-activated Ca2+ channels) a second, automatically superimposed defense mechanism. A third defensive mechanism may be effectuated by the secretory lectins of the trichocyst tip; they may inhibit toxicyst exocytosis in Dileptus by crosslinking surface proteins (an effect mimicked in Paramecium by antibodies against cell surface components). Some of the proteins, body and tip, are glycosylated as visualized by binding of exogenous lectins. This reflects the biogenetic pathway, from the endoplasmic reticulum via the Golgi apparatus, which is also supported by details from molecular biology. There are fragile links connecting the matrix of a trichocyst with its membrane; these may signal the filling state, full or empty, before and after tmp release upon exocytosis, respectively. This is supported by experimentally produced "frustrated exocytosis", i.e. membrane fusion without contents release, followed by membrane resealing and entry in a new cycle of reattachment for stimulated exocytosis. There are some more puzzles to be solved: Considering the absence of any detectable Ca2+ and of acidity in the organelle, what causes the striking effects of silencing the genes of some specific Ca2+ -release channels and of subunits of the H+ -ATPase? What determines the inherent polarity of a trichocyst? What precisely causes the inability of trichocyst mutants to dock at the cell membrane? Many details now call for further experimental work to unravel more secrets about these fascinating organelles. PMID- 27251228 TI - Structure and inhibition analysis of the mouse SAD-B C-terminal fragment. AB - The SAD (synapses of amphids defective) kinases, including SAD-A and SAD-B, play important roles in the regulation of neuronal development, cell cycle, and energy metabolism. Our recent study of mouse SAD-A identified a unique autoinhibitory sequence (AIS), which binds at the junction of the kinase domain (KD) and the ubiquitin-associated (UBA) domain and exerts autoregulation in cooperation with UBA. Here, we report the crystal structure of the mouse SAD-B C-terminal fragment including the AIS and the kinase-associated domain 1 (KA1) at 2.8 A resolution. The KA1 domain is structurally conserved, while the isolated AIS sequence is highly flexible and solvent-accessible. Our biochemical studies indicated that the SAD-B AIS exerts the same autoinhibitory role as that in SAD-A. We believe that the flexible isolated AIS sequence is readily available for interaction with KD-UBA and thus inhibits SAD-B activity. PMID- 27251229 TI - Effects of 22 CYP2D6 Genetic Variations Newly Identified in Chinese Population on Olanzapine Metabolism in vitro. AB - The objective of this study was to assess the catalytic activity of 22 novel CYP2D6 allelic variants (2D6*87-*98, R25Q, F164L, E215K, F219S, V327M, D336N, V342M, R344Q, R440C and R497C) to olanzapine in vitro. Their protein products expressed in Spodoptera frugiperda 21 (Sf21) insect cells were incubated with olanzapine 100-2,000 MUmol/l for 30 min. The kinetic parameters of Km, Vmax and intrinsic clearance were determined by 2-hydroxymethylolanzapine, the metabolite of olanzapine mediated by CYP2D6, using ultra-performance liquid chromatography tandem mass spectrometry. Results showed that the kinetic parameters of 2 alleles, CYP2D6*92 and 2D6*96, could not be detected; 17 allelic variants, CYP2D6*87-*88, 2D6*90-*91, 2D6*93-*95, 2D6*97, R25Q, F164L, E215K, F219S, V327M, V342M, R344Q, R440C and R497C, significantly reduced the intrinsic clearance of olanzapine; 2 variants, CYP2D6*89 and 2D6*98, increased the intrinsic clearance of olanzapine; no difference was found in intrinsic clearance of D336N. Furthermore, 6 alleles, CYP2D6*87, 2D6*88, 2D6*91, 2D6*93, 2D6*97 and R497C, exhibited higher Km values in a range of 120.80-217.56% relative to wild-type CYP2D6*1. The research demonstrated the metabolic phenotype of the 22 novel CYP2D6 variants for olanzapine that were different from probe drugs we used previously and might provide beneficial information to the personalized medicine of olanzapine. PMID- 27251230 TI - Evaluating the responses of a territorial solitary carnivore to potential mates and competitors. AB - Successful communication is critical to the fitness of individuals and maintenance of populations, but less is known regarding the social contexts and reactions to scent marking by other individuals in solitary carnivores, including pumas. We evaluated the responses of resident male pumas to visitation and scent marking by potential competitors (other male pumas) and potential mates (female pumas) by capturing and marking 46 pumas (Puma concolor), and documenting scent marking behaviours using motion-triggered video cameras. By comparing resident male puma visitation rates and communication behaviours in response to either male or female visitors, we found that their visitation and communication behaviours were best explained by the combination of visitation by both competitors and potential mates. Resident males returned to scent marking sites more quickly and increased their rate of flehmen response after visitation by a females, while they increased their rate of visitation and duration of visits in response to other males. Male pumas also visited less frequently in summer and autumn when female visitation rates were lower, but males created nearly twice as many scrapes during these visits. This study suggests that advertising for mates when scent marking may sometimes overshadow the importance of deterring competitors and claiming territory. PMID- 27251231 TI - Diaphragmatic excursion measurement in emergency patients with acute dyspnea: toward a new diagnostic tool? AB - INTRODUCTION: During acute dyspnea (AD), respiratory exhaustion is mainly due to diaphragm fatigue. The primary objective was to validate interobserver reproducibility of diaphragmatic excursion (DE) in emergency department (ED) patients admitted for AD. The secondary objectives were to assess the feasibility of DE measurement and intraobserver reproducibility. Finally, we examined whether the DE value was associated with a need for noninvasive ventilation (NIV). MATERIALS: This was a monocentric, prospective, technical reproducibility study. Adult patients in spontaneous ventilation admitted for AD were included. Two operators carried out 2 consecutive diaphragm excursion measurements each on the right and left hemidiaphragms. RESULTS: Twenty-four patients were analyzed. The feasibility was 96% on the right and 67% on the left. The interobserver concordance between the 2 measures was 0.80 (95% confidence interval [CI], 0.59 0.91) (average difference, -0.07+/-0.48 cm) on the right and 0.59 (95% CI, 0.19 0.82) (average difference, 0.30+/-0.91 cm) on the left. For right DE values inferior to 2.3 cm, the interobserver concordance between measures was 0.92 (95% CI, 0.78-0.97). The intraobserver concordance was 0.89 (95% CI, 0.81-0.94) (average difference, 0.02+/-0.35 cm) on the right and 0.90 (95% CI, 0.82-0.95) (average difference,-0.06+/-0.45 cm) on the left. When the DE was greater than 2 cm, no patient required NIV. CONCLUSION: Diaphragmatic excursion measurement of the right diaphragm is feasible, with good interobserver and intraobserver reproducibility in ED patients admitted for AD. When the DE value is greater than 2 cm at admission, no subsequent NIV is required. PMID- 27251232 TI - Late lead perforation presenting as acute shoulder pain. PMID- 27251233 TI - Giant Seebeck effect in Ge-doped SnSe. AB - Thermoelectric materials may contribute in the near future as new alternative sources of sustainable energy. Unprecedented thermoelectric properties in p-type SnSe single crystals have been recently reported, accompanied by extremely low thermal conductivity in polycrystalline samples. In order to enhance thermoelectric efficiency through proper tuning of this material we report a full structural characterization and evaluation of the thermoelectric properties of novel Ge-doped SnSe prepared by a straightforward arc-melting method, which yields nanostructured polycrystalline samples. Ge does not dope the system in the sense of donating carriers, yet the electrical properties show a semiconductor behavior with resistivity values higher than that of the parent compound, as a consequence of nanostructuration, whereas the Seebeck coefficient is higher and thermal conductivity lower, favorable to a better ZT figure of merit. PMID- 27251234 TI - Does caspase-12 suppress inflammasome activation? PMID- 27251236 TI - Toxic control. PMID- 27251235 TI - Dark satanic wings. PMID- 27251237 TI - Seeing farther. PMID- 27251238 TI - The developing world needs basic research too. PMID- 27251250 TI - Marine ecologists take to the skies to study coral reefs. PMID- 27251252 TI - Tiny 'chipsat' spacecraft set for first flight. PMID- 27251251 TI - Biology's big funders boost eLife. Open-access journal nets L25 million in support until 2022. PMID- 27251254 TI - Two-hundred-terabyte maths proof is largest ever. PMID- 27251253 TI - US advised to stick with troubled fusion reactor ITER. PMID- 27251255 TI - Why the historic deal to expand US chemical regulation matters. PMID- 27251256 TI - Correction. PMID- 27251257 TI - Why South Korea is the world's biggest investor in research. PMID- 27251258 TI - The snot-spattered experiments that show how far sneezes really spread. PMID- 27251259 TI - Industrial research: Drug companies must adopt green chemistry. PMID- 27251260 TI - Conservation: The seas cannot be saved on a budget of breadcrumbs. PMID- 27251264 TI - Chernobyl anniversary: Ukraine should cut back nuclear power. PMID- 27251265 TI - Invasive species: Bee-hawking hornet already in line of fire. PMID- 27251266 TI - Genome editing: Broad Institute keeps CRISPR tools open. PMID- 27251267 TI - China: Industry parks limit circular economy. PMID- 27251268 TI - Environmental costs: Revive China's green GDP programme. PMID- 27251269 TI - Walter Kohn (1923-2016). PMID- 27251270 TI - Planetary science: Pluto's polygons explained. PMID- 27251271 TI - Microbiology: Pumping persisters. PMID- 27251272 TI - Structural biology: A photo shoot of plant photosystem II. PMID- 27251273 TI - Archaeology: Neanderthals built underground. PMID- 27251274 TI - Geophysics: Earth's core problem. PMID- 27251277 TI - Regulation of black-hole accretion by a disk wind during a violent outburst of V404 Cygni. AB - Accretion of matter onto black holes is universally associated with strong radiative feedback and powerful outflows. In particular, black-hole transients have outflows whose properties are strongly coupled to those of the accretion flow. This includes X-ray winds of ionized material, expelled from the accretion disk encircling the black hole, and collimated radio jets. Very recently, a distinct optical variability pattern has been reported in the transient stellar mass black hole V404 Cygni, and interpreted as disrupted mass flow into the inner regions of its large accretion disk. Here we report observations of a sustained outer accretion disk wind in V404 Cyg, which is unlike any seen hitherto. We find that the outflowing wind is neutral, has a large covering factor, expands at one per cent of the speed of light and triggers a nebular phase once accretion drops sharply and the ejecta become optically thin. The large expelled mass (>10(-8) solar masses) indicates that the outburst was prematurely ended when a sizeable fraction of the outer disk was depleted by the wind, detaching the inner regions from the rest of the disk. The luminous, but brief, accretion phases shown by transients with large accretion disks imply that this outflow is probably a fundamental ingredient in regulating mass accretion onto black holes. PMID- 27251276 TI - Structure of spinach photosystem II-LHCII supercomplex at 3.2 A resolution. AB - During photosynthesis, the plant photosystem II core complex receives excitation energy from the peripheral light-harvesting complex II (LHCII). The pathways along which excitation energy is transferred between them, and their assembly mechanisms, remain to be deciphered through high-resolution structural studies. Here we report the structure of a 1.1-megadalton spinach photosystem II-LHCII supercomplex solved at 3.2 A resolution through single-particle cryo-electron microscopy. The structure reveals a homodimeric supramolecular system in which each monomer contains 25 protein subunits, 105 chlorophylls, 28 carotenoids and other cofactors. Three extrinsic subunits (PsbO, PsbP and PsbQ), which are essential for optimal oxygen-evolving activity of photosystem II, form a triangular crown that shields the Mn4CaO5-binding domains of CP43 and D1. One major trimeric and two minor monomeric LHCIIs associate with each core-complex monomer, and the antenna-core interactions are reinforced by three small intrinsic subunits (PsbW, PsbH and PsbZ). By analysing the closely connected interfacial chlorophylls, we have obtained detailed insights into the energy transfer pathways between the antenna and core complexes. PMID- 27251278 TI - Vigorous convection as the explanation for Pluto's polygonal terrain. AB - Pluto's surface is surprisingly young and geologically active. One of its youngest terrains is the near-equatorial region informally named Sputnik Planum, which is a topographic basin filled by nitrogen (N2) ice mixed with minor amounts of CH4 and CO ices. Nearly the entire surface of the region is divided into irregular polygons about 20-30 kilometres in diameter, whose centres rise tens of metres above their sides. The edges of this region exhibit bulk flow features without polygons. Both thermal contraction and convection have been proposed to explain this terrain, but polygons formed from thermal contraction (analogous to ice-wedges or mud-crack networks) of N2 are inconsistent with the observations on Pluto of non-brittle deformation within the N2-ice sheet. Here we report a parameterized convection model to compute the Rayleigh number of the N2 ice and show that it is vigorously convecting, making Rayleigh-Benard convection the most likely explanation for these polygons. The diameter of Sputnik Planum's polygons and the dimensions of the 'floating mountains' (the hills of of water ice along the edges of the polygons) suggest that its N2 ice is about ten kilometres thick. The estimated convection velocity of 1.5 centimetres a year indicates a surface age of only around a million years. PMID- 27251279 TI - Convection in a volatile nitrogen-ice-rich layer drives Pluto's geological vigour. AB - The vast, deep, volatile-ice-filled basin informally named Sputnik Planum is central to Pluto's vigorous geological activity. Composed of molecular nitrogen, methane, and carbon monoxide ices, but dominated by nitrogen ice, this layer is organized into cells or polygons, typically about 10 to 40 kilometres across, that resemble the surface manifestation of solid-state convection. Here we report, on the basis of available rheological measurements, that solid layers of nitrogen ice with a thickness in excess of about one kilometre should undergo convection for estimated present-day heat-flow conditions on Pluto. More importantly, we show numerically that convective overturn in a several-kilometre thick layer of solid nitrogen can explain the great lateral width of the cells. The temperature dependence of nitrogen-ice viscosity implies that the ice layer convects in the so-called sluggish lid regime, a unique convective mode not previously definitively observed in the Solar System. Average surface horizontal velocities of a few centimetres a year imply surface transport or renewal times of about 500,000 years, well under the ten-million-year upper-limit crater retention age for Sputnik Planum. Similar convective surface renewal may also occur on other dwarf planets in the Kuiper belt, which may help to explain the high albedos shown by some of these bodies. PMID- 27251280 TI - Attosecond nonlinear polarization and light-matter energy transfer in solids. AB - Electric-field-induced charge separation (polarization) is the most fundamental manifestation of the interaction of light with matter and a phenomenon of great technological relevance. Nonlinear optical polarization produces coherent radiation in spectral ranges inaccessible by lasers and constitutes the key to ultimate-speed signal manipulation. Terahertz techniques have provided experimental access to this important observable up to frequencies of several terahertz. Here we demonstrate that attosecond metrology extends the resolution to petahertz frequencies of visible light. Attosecond polarization spectroscopy allows measurement of the response of the electronic system of silica to strong (more than one volt per angstrom) few-cycle optical (about 750 nanometres) fields. Our proof-of-concept study provides time-resolved insight into the attosecond nonlinear polarization and the light-matter energy transfer dynamics behind the optical Kerr effect and multi-photon absorption. Timing the nonlinear polarization relative to the driving laser electric field with sub-30-attosecond accuracy yields direct quantitative access to both the reversible and irreversible energy exchange between visible-infrared light and electrons. Quantitative determination of dissipation within a signal manipulation cycle of only a few femtoseconds duration (by measurement and ab initio calculation) reveals the feasibility of dielectric optical switching at clock rates above 100 terahertz. The observed sub-femtosecond rise of energy transfer from the field to the material (for a peak electric field strength exceeding 2.5 volts per angstrom) in turn indicates the viability of petahertz-bandwidth metrology with a solid-state device. PMID- 27251275 TI - Proteogenomics connects somatic mutations to signalling in breast cancer. AB - Somatic mutations have been extensively characterized in breast cancer, but the effects of these genetic alterations on the proteomic landscape remain poorly understood. Here we describe quantitative mass-spectrometry-based proteomic and phosphoproteomic analyses of 105 genomically annotated breast cancers, of which 77 provided high-quality data. Integrated analyses provided insights into the somatic cancer genome including the consequences of chromosomal loss, such as the 5q deletion characteristic of basal-like breast cancer. Interrogation of the 5q trans-effects against the Library of Integrated Network-based Cellular Signatures, connected loss of CETN3 and SKP1 to elevated expression of epidermal growth factor receptor (EGFR), and SKP1 loss also to increased SRC tyrosine kinase. Global proteomic data confirmed a stromal-enriched group of proteins in addition to basal and luminal clusters, and pathway analysis of the phosphoproteome identified a G-protein-coupled receptor cluster that was not readily identified at the mRNA level. In addition to ERBB2, other amplicon associated highly phosphorylated kinases were identified, including CDK12, PAK1, PTK2, RIPK2 and TLK2. We demonstrate that proteogenomic analysis of breast cancer elucidates the functional consequences of somatic mutations, narrows candidate nominations for driver genes within large deletions and amplified regions, and identifies therapeutic targets. PMID- 27251281 TI - Oil sands operations as a large source of secondary organic aerosols. AB - Worldwide heavy oil and bitumen deposits amount to 9 trillion barrels of oil distributed in over 280 basins around the world, with Canada home to oil sands deposits of 1.7 trillion barrels. The global development of this resource and the increase in oil production from oil sands has caused environmental concerns over the presence of toxic compounds in nearby ecosystems and acid deposition. The contribution of oil sands exploration to secondary organic aerosol formation, an important component of atmospheric particulate matter that affects air quality and climate, remains poorly understood. Here we use data from airborne measurements over the Canadian oil sands, laboratory experiments and a box-model study to provide a quantitative assessment of the magnitude of secondary organic aerosol production from oil sands emissions. We find that the evaporation and atmospheric oxidation of low-volatility organic vapours from the mined oil sands material is directly responsible for the majority of the observed secondary organic aerosol mass. The resultant production rates of 45-84 tonnes per day make the oil sands one of the largest sources of anthropogenic secondary organic aerosols in North America. Heavy oil and bitumen account for over ten per cent of global oil production today, and this figure continues to grow. Our findings suggest that the production of the more viscous crude oils could be a large source of secondary organic aerosols in many production and refining regions worldwide, and that such production should be considered when assessing the environmental impacts of current and planned bitumen and heavy oil extraction projects globally. PMID- 27251282 TI - Experimental determination of the electrical resistivity of iron at Earth's core conditions. AB - Earth continuously generates a dipole magnetic field in its convecting liquid outer core by a self-sustained dynamo action. Metallic iron is a dominant component of the outer core, so its electrical and thermal conductivity controls the dynamics and thermal evolution of Earth's core. However, in spite of extensive research, the transport properties of iron under core conditions are still controversial. Since free electrons are a primary carrier of both electric current and heat, the electron scattering mechanism in iron under high pressure and temperature holds the key to understanding the transport properties of planetary cores. Here we measure the electrical resistivity (the reciprocal of electrical conductivity) of iron at the high temperatures (up to 4,500 kelvin) and pressures (megabars) of Earth's core in a laser-heated diamond-anvil cell. The value measured for the resistivity of iron is even lower than the value extrapolated from high-pressure, low-temperature data using the Bloch-Gruneisen law, which considers only the electron-phonon scattering. This shows that the iron resistivity is strongly suppressed by the resistivity saturation effect at high temperatures. The low electrical resistivity of iron indicates the high thermal conductivity of Earth's core, suggesting rapid core cooling and a young inner core less than 0.7 billion years old. Therefore, an abrupt increase in palaeomagnetic field intensity around 1.3 billion years ago may not be related to the birth of the inner core. PMID- 27251283 TI - Direct measurement of thermal conductivity in solid iron at planetary core conditions. AB - The conduction of heat through minerals and melts at extreme pressures and temperatures is of central importance to the evolution and dynamics of planets. In the cooling Earth's core, the thermal conductivity of iron alloys defines the adiabatic heat flux and therefore the thermal and compositional energy available to support the production of Earth's magnetic field via dynamo action. Attempts to describe thermal transport in Earth's core have been problematic, with predictions of high thermal conductivity at odds with traditional geophysical models and direct evidence for a primordial magnetic field in the rock record. Measurements of core heat transport are needed to resolve this difference. Here we present direct measurements of the thermal conductivity of solid iron at pressure and temperature conditions relevant to the cores of Mercury-sized to Earth-sized planets, using a dynamically laser-heated diamond-anvil cell. Our measurements place the thermal conductivity of Earth's core near the low end of previous estimates, at 18-44 watts per metre per kelvin. The result is in agreement with palaeomagnetic measurements indicating that Earth's geodynamo has persisted since the beginning of Earth's history, and allows for a solid inner core as old as the dynamo. PMID- 27251284 TI - The industrial melanism mutation in British peppered moths is a transposable element. AB - Discovering the mutational events that fuel adaptation to environmental change remains an important challenge for evolutionary biology. The classroom example of a visible evolutionary response is industrial melanism in the peppered moth (Biston betularia): the replacement, during the Industrial Revolution, of the common pale typica form by a previously unknown black (carbonaria) form, driven by the interaction between bird predation and coal pollution. The carbonaria locus has been coarsely localized to a 200-kilobase region, but the specific identity and nature of the sequence difference controlling the carbonaria-typica polymorphism, and the gene it influences, are unknown. Here we show that the mutation event giving rise to industrial melanism in Britain was the insertion of a large, tandemly repeated, transposable element into the first intron of the gene cortex. Statistical inference based on the distribution of recombined carbonaria haplotypes indicates that this transposition event occurred around 1819, consistent with the historical record. We have begun to dissect the mode of action of the carbonaria transposable element by showing that it increases the abundance of a cortex transcript, the protein product of which plays an important role in cell-cycle regulation, during early wing disc development. Our findings fill a substantial knowledge gap in the iconic example of microevolutionary change, adding a further layer of insight into the mechanism of adaptation in response to natural selection. The discovery that the mutation itself is a transposable element will stimulate further debate about the importance of 'jumping genes' as a source of major phenotypic novelty. PMID- 27251285 TI - The gene cortex controls mimicry and crypsis in butterflies and moths. AB - The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection. Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and whether this control shows any commonality across the 160,000 moth and 17,000 butterfly species. Here, we use fine-scale mapping with population genomics and gene expression analyses to identify a gene, cortex, that regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast-evolving subfamily of the otherwise highly conserved fizzy family of cell-cycle regulators, suggesting that it probably regulates pigmentation patterning by regulating scale cell development. In parallel with findings in the peppered moth (Biston betularia), our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects. PMID- 27251286 TI - Early Neanderthal constructions deep in Bruniquel Cave in southwestern France. AB - Very little is known about Neanderthal cultures, particularly early ones. Other than lithic implements and exceptional bone tools, very few artefacts have been preserved. While those that do remain include red and black pigments and burial sites, these indications of modernity are extremely sparse and few have been precisely dated, thus greatly limiting our knowledge of these predecessors of modern humans. Here we report the dating of annular constructions made of broken stalagmites found deep in Bruniquel Cave in southwest France. The regular geometry of the stalagmite circles, the arrangement of broken stalagmites and several traces of fire demonstrate the anthropogenic origin of these constructions. Uranium-series dating of stalagmite regrowths on the structures and on burnt bone, combined with the dating of stalagmite tips in the structures, give a reliable and replicated age of 176.5 thousand years (+/-2.1 thousand years), making these edifices among the oldest known well-dated constructions made by humans. Their presence at 336 metres from the entrance of the cave indicates that humans from this period had already mastered the underground environment, which can be considered a major step in human modernity. PMID- 27251287 TI - A shared neural ensemble links distinct contextual memories encoded close in time. AB - Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Several findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two contexts are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged mice, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by ageing could affect the temporal structure of memories, thus impairing efficient recall of related information. PMID- 27251288 TI - Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury. AB - Myocardial infarction results in compromised myocardial function and heart failure owing to insufficient cardiomyocyte self-renewal. Unlike many vertebrates, mammalian hearts have only a transient neonatal renewal capacity. Reactivating primitive reparative ability in the mature mammalian heart requires knowledge of the mechanisms that promote early heart repair. By testing an established Hippo-deficient heart regeneration mouse model for factors that promote renewal, here we show that the expression of Pitx2 is induced in injured, Hippo-deficient ventricles. Pitx2-deficient neonatal mouse hearts failed to repair after apex resection, whereas adult mouse cardiomyocytes with Pitx2 gain of-function efficiently regenerated after myocardial infarction. Genomic analyses indicated that Pitx2 activated genes encoding electron transport chain components and reactive oxygen species scavengers. A subset of Pitx2 target genes was cooperatively regulated with the Hippo pathway effector Yap. Furthermore, Nrf2, a regulator of the antioxidant response, directly regulated the expression and subcellular localization of Pitx2. Pitx2 mutant myocardium had increased levels of reactive oxygen species, while antioxidant supplementation suppressed the Pitx2 loss-of-function phenotype. These findings reveal a genetic pathway activated by tissue damage that is essential for cardiac repair. PMID- 27251289 TI - Feedback modulation of cholesterol metabolism by the lipid-responsive non-coding RNA LeXis. AB - Liver X receptors (LXRs) are transcriptional regulators of cellular and systemic cholesterol homeostasis. Under conditions of excess cholesterol, LXR activation induces the expression of several genes involved in cholesterol efflux, facilitates cholesterol esterification by promoting fatty acid synthesis, and inhibits cholesterol uptake by the low-density lipoprotein receptor. The fact that sterol content is maintained in a narrow range in most cell types and in the organism as a whole suggests that extensive crosstalk between regulatory pathways must exist. However, the molecular mechanisms that integrate LXRs with other lipid metabolic pathways are incompletely understood. Here we show that ligand activation of LXRs in mouse liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as a mediator of this effect. Hepatic LeXis expression is robustly induced in response to a Western diet (high in fat and cholesterol) or to pharmacological LXR activation. Raising or lowering LeXis levels in the liver affects the expression of genes involved in cholesterol biosynthesis and alters the cholesterol levels in the liver and plasma. LeXis interacts with and affects the DNA interactions of RALY, a heterogeneous ribonucleoprotein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the mouse liver. These findings outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms that coordinate sterol homeostasis. PMID- 27251290 TI - Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. AB - The epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved treatments for non-small cell lung cancers harbouring activating mutations in the EGFR kinase, but resistance arises rapidly, most frequently owing to the secondary T790M mutation within the ATP site of the receptor. Recently developed mutant-selective irreversible inhibitors are highly active against the T790M mutant, but their efficacy can be compromised by acquired mutation of C797, the cysteine residue with which they form a key covalent bond. All current EGFR TKIs target the ATP site of the kinase, highlighting the need for therapeutic agents with alternative mechanisms of action. Here we describe the rational discovery of EAI045, an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor. The crystal structure shows that the compound binds an allosteric site created by the displacement of the regulatory C-helix in an inactive conformation of the kinase. The compound inhibits L858R/T790M-mutant EGFR with low-nanomolar potency in biochemical assays. However, as a single agent it is not effective in blocking EGFR-driven proliferation in cells owing to differential potency on the two subunits of the dimeric receptor, which interact in an asymmetric manner in the active state. We observe marked synergy of EAI045 with cetuximab, an antibody therapeutic that blocks EGFR dimerization, rendering the kinase uniformly susceptible to the allosteric agent. EAI045 in combination with cetuximab is effective in mouse models of lung cancer driven by EGFR(L858R/T790M) and by EGFR(L858R/T790M/C797S), a mutant that is resistant to all currently available EGFR TKIs. More generally, our findings illustrate the utility of purposefully targeting allosteric sites to obtain mutant-selective inhibitors. PMID- 27251291 TI - Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes. AB - Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm. Hundreds of assembly factors, organized into sequential functional groups, facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these assembly factors function are largely unknown. Here we use cryo electron microscopy to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged assembly factor Nog2. Our data pinpoint the locations and determine the structures of over 20 assembly factors, which are enriched in two areas: an arc region extending from the central protuberance to the polypeptide tunnel exit, and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S ribosomal RNAs. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant assembly factors and functional ribosomal RNA elements, manifesting their critical roles in structural remodelling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodelling events before nuclear export: rotation of the 5S ribonucleoprotein, construction of the active centre and ITS2 removal. The rich structural information in our structures provides a framework to dissect molecular roles of diverse assembly factors in eukaryotic ribosome assembly. PMID- 27251295 TI - Technique and outcome of post-mastectomy adjuvant chest wall radiotherapy-the role of tissue-equivalent bolus in reducing risk of local recurrence. AB - OBJECTIVE: Adjuvant chest wall radiotherapy is used in patients with high-risk histological features post-mastectomy to reduce the risk of locoregional recurrence. Treatment can be given with or without a tissue-equivalent bolus to increase skin surface dose. The additional benefit of using a bolus remains unclear; however, it is known to be associated with a higher incidence of skin toxicity. This study compared chest wall recurrence and skin toxicity in patients treated with and without a bolus. METHODS: This retrospective cohort study reviewed 314 consecutive patients who received chest wall radiotherapy between 2005 and 2010. Data were collected on histological, demographic and treatment parameters and on the incidence and grade of acute skin reactions. Treatment outcomes analyzed included chest wall recurrence, disease-free survival and overall survival (OS). RESULTS: 101 patients received treatment with a bolus; 213 patients received treatment without a bolus. A significantly higher incidence of acute skin toxicity was seen in the bolus treatment group (p = 0.002). One patient treated with a bolus developed chest wall recurrence compared with four patients treated without a bolus. No statistically significant difference could be shown between the two groups. 66 (21%) patients had metastatic relapse. Median time to relapse was 29.5 months and OS was 76% in both treatment groups. CONCLUSION: No statistically significant difference in chest wall recurrence can be demonstrated between patients treated with and without a bolus. ADVANCES IN KNOWLEDGE: This study is consistent with limited previous literature and invites further evaluation of the role of a bolus in post-mastectomy chest wall radiotherapy, especially considering the increased toxicity that the use of a bolus generates. PMID- 27251294 TI - Cryptosporidium and Giardia taxa in faecal samples from animals in catchments supplying the city of Melbourne with drinking water (2011 to 2015). AB - BACKGROUND: In a long-term program to monitor pathogens in water catchments serving the City of Melbourne in the State of Victoria in Australia, we detected and genetically characterised Cryptosporidium and Giardia in faecal samples from various animals in nine water reservoir areas over a period of 4 years (July 2011 to November 2015). METHODS: This work was conducted using PCR-based single-strand conformation polymorphism (SSCP) and phylogenetic analyses of portions of the small subunit of ribosomal RNA (SSU) and 60 kDa glycoprotein (gp60) genes for Cryptosporidium, and triose-phosphate isomerase (tpi) gene for Giardia. RESULTS: The prevalence of Cryptosporidium was 1.62 % (69 of 4,256 samples); 25 distinct sequence types were defined for pSSU, and six for gp60 which represented C. hominis (genotype Ib - subgenotype IbA10G2), C. cuniculus (genotype Vb - subgenotypes VbA26, and VbA25), and C. canis, C. fayeri, C. macropodum, C. parvum, C. ryanae, Cryptosporidium sp. "duck" genotype, C. suis and C. ubiquitum as well as 12 novel SSU sequence types. The prevalence of Giardia was 0.31 % (13 of 4,256 samples); all three distinct tpi sequence types defined represented assemblage A of G. duodenalis. CONCLUSIONS: Of the 34 sequence types (genotypes) characterized here, five and one have been recorded previously for Cryptosporidium and Giardia, respectively, from humans. Novel genotypes of Cryptosporidium and Giardia were recorded for SSU (n = 12), gp60 (n = 4) and tpi (n = 1); the zoonotic potential of these novel genotypes is presently unknown. Future work will continue to monitor the prevalence of Cryptosporidium and Giardia genotypes in animals in these catchments, and expand investigations to humans. Nucleotide sequences reported in this paper are available in the GenBank database under accession nos. KU531647-KU531718. PMID- 27251296 TI - Evaluation of intramyocellular and extramyocellular lipids in the paraspinal muscle in patients with chronic low back pain using MR spectroscopy: preliminary results. AB - OBJECTIVE: To analyze the intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL) in the psoas muscle (Pm) and multifidus muscle (Mm) using MR spectroscopy (MRS) in patients with chronic low back pain (CLBP) and asymptomatic volunteers. METHODS: This prospective study had institutional review board approval, and written informed consent was obtained from all individual participants. 20 patients with CLBP (mean age, 49.8 +/- 12.5 years; age range, 28 66 years) with low back pain (LBP) duration of >=3 months and asymptomatic volunteers (mean age, 44.0 +/- 12.8 years; age range, 28-65 years) underwent MRS for the quantification of IMCL and EMCL of the right Pm and Mm in a volume of interest at the intervertebral level of L4 through L5. We compared patients with CLBP and asymptomatic volunteers for age and body mass index (BMI), IMCL and EMCL of Pm and Mm. The Mann-Whitney U-test was used for significant difference testing, with p-value <0.05 indicating statistical significance. RESULTS: No statistically significant differences were observed in the age and BMI of patients with CLBP and asymptomatic volunteers. There was no statistically significant difference in the EMCL and IMCL in Pm between the two groups. EMCL in Mm was not statistically significantly different; the IMCL of patients with CLBP was significantly higher than that of asymptomatic volunteers (p < 0.05). CONCLUSION: MRS demonstrates that IMCL in the Mm of patients with CLBP is significantly higher than that of asymptomatic volunteers. The increase of IMCL in the Mm may be a characteristic finding in CLBP. ADVANCES IN KNOWLEDGE: We investigated the detail of the fat content in the paraspinal muscles in patients CLBP and asymptomatic volunteers. The increase of fat content in the Mm of patients with LBP on previous studies was demonstrated to be the increase of IMCL. PMID- 27251298 TI - A Novel Approach: Local Resection for Ampullary GIST-Case Report and Review of Literature. PMID- 27251297 TI - Neuroanatomic pathways associated with monoaminergic dysregulation after stroke. AB - OBJECTIVE: We examined the complex relationship between lesion location, symptoms of depression (affective and apathetic), and monoamine dysfunction after stroke. METHODS: Magnetic resonance imaging was performed on 48 post-stroke patients that had been assessed for affective and apathetic symptoms using the Hospital Anxiety and Depression Scale and the Apathy Scale, respectively. Noradrenalin (NA), dopamine (DA), their metabolites, and a metabolite of serotonin (5-HT) were measured using 24-h urine samples, and 5-HT and 3-methoxy-4-hydroxyphenylglycol were measured using blood samples. We developed a statistical parametric map that displayed the associations between lesion location and both positive and negative alterations of monoamines and their metabolites. RESULTS: Multivariate analysis indicated that basal ganglia lesions and 5-HT showed relationships with affective symptoms, whereas homovanillic acid was related to apathetic symptoms. Univariate analysis showed no such relationships. However, decreases in NA and DA and increases in NA and DA turnover were related to lesions in the brainstem, whereas increases in NA and DA as well as decreases in NA and DA turnover were related to cortical and/or striatum lesions. 5-HT turnover data showed a pattern opposite to that seen for NA and DA turnover. CONCLUSIONS: Monoaminergic neuronal pathways are controlled by both receptor-mediated feedback mechanisms and turnover; thus, depletion of monoamines is not the only cause of depression and apathy. Moreover, the monoamine neuronal network might be divided into two branches, catecholamine (NA and DA) and 5-HT, both of which are anatomically and functionally interconnected and could respectively influence apathetic and affective symptoms of depression. PMID- 27251299 TI - Gastrocolic Fistula as a Presentation of Concomitant Gastric and Colon Cancer in a Patient with a History of Metastatic Pancreatic Adenocarcinoma. PMID- 27251301 TI - Correction to "Toward Nonadiabatic Dynamics of Multichromophore Complexes: A Scalable GPU-Accelerated Exciton Framework. PMID- 27251300 TI - Diagnostic and Prognostic Value of miR-1287 in Colorectal Cancer. AB - INTRODUCTION: MicroRNAs are non-coding RNAs that regulate the gene expression at post-transcriptional level. This futuristic study characterized the contribution of miR-1287 to the colorectal cancer (CRC) tumorigenesis. METHODS: The real-time reverse transcription-polymerase chain reaction was used to examine miR-1287 expression levels, prospectively in 40 pairs of CRC tissue samples and adjacent noncancerous tissues (>2 cm from cancer tissue). RESULTS: No significant relationship was found between miR-1287 expression levels and clinicopathological features. Showing significant changes overall, MiR-1287 was significantly upregulated in the group of CRC samples compared with matched noncancerous tissue samples. A receiver operating characteristic (ROC) curve also showed ROC area (AROC) of 34 % with 1.0 and 0.02 sensitivity and specificity, respectively. Expression of miR-1287, with a value of 0.34, P value = 1.98, and P > 0.05, revealed that this microRNA has a low sensitivity and specificity to be regarded as a tumor marker. CONCLUSIONS: With regard to recent increased rate of CRC in the world, the present study may be a contribution, though very small, in the diagnosis and consequently in the treatment of CRC patients. PMID- 27251303 TI - Factors affecting outcome in myasthenia gravis. AB - INTRODUCTION AND METHODS: Information from myasthenia gravis (MG) patients treated and evaluated for at least 2 years between 1980 and 2014 was reviewed to assess the effect of demographics, antibody status and titer, thymus histology, and clinical severity on outcome after 2, 5, and 10 years of treatment. RESULTS: Among 268 patients, 74% had acetylcholine receptor antibodies, 5% had muscle specific tyrosine kinase-antibodies, and 22% had neither. Optimal outcome was achieved by 64% of patients at 2 years of follow-up, 73% at 5 years, and 75% after 10 years. Optimal outcome was achieved more often in patients with late onset, in those who had thymectomy, and in those with ocular-only disease at maximum severity. The only consistent independent predictor of optimal outcome was onset after age 50 years on multivariate analysis. CONCLUSIONS: Prognosis is favorable for the majority of MG patients, regardless of age, maximum disease severity, or antibody status. Muscle Nerve, 2016 Muscle Nerve 54: 1041-1049, 2016. PMID- 27251302 TI - Going global: the new era of mapping modifications in RNA. AB - The post-transcriptional modification of RNA by the addition of one or more chemical groups has been known for over 50 years. These chemical modifications, once thought to be static, are now being discovered to play key regulatory roles in gene expression. The advent of massive parallel sequencing of RNA (RNA-seq) now allows us to probe the complexity of cellular RNA and how chemically altering RNA structure expands the RNA vocabulary. Here we present an overview of the various strategies and technologies that are available to profile RNA chemical modifications at the cellular level. These strategies can be characterized as targeted and untargeted approaches: targeted strategies are developed for one single chemical modification while untargeted strategies are more broadly applicable to a range of such chemical changes. Key for all of these approaches is the ability to locate modifications within the RNA sequence. While most of these methods are built upon an RNA-Seq pipeline, alternative approaches based on mass spectrometry or conventional DNA sequencing retain value in the overall analysis process. We also look forward toward future opportunities and technologies that may expand the types of modifications that can be globally profiled. Given the ever increasing recognition that these RNA chemical modifications play important biological roles, a variety of methods, preferably orthogonal approaches, will be required to globally identify, validate and quantify RNA chemical modifications found in the transcriptome. WIREs RNA 2017, 8:e1367. doi: 10.1002/wrna.1367 For further resources related to this article, please visit the WIREs website. PMID- 27251304 TI - Protocol for regional implementation of collaborative lung function testing. PMID- 27251305 TI - Epidemiological characteristics of human prion diseases. AB - Human prion diseases are a group of transmissible, progressive, and invariably fatal neurodegenerative disorders, which include Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia. Human prion diseases affect approximately 1-2 persons per million worldwide annually, occurring in sporadic, inherited, and acquired forms. These diseases have attracted both scientific and public attention not only because of their mysterious pathogen, but also due to their considerable threat to public health since the emergence of the variant CJD.There are still no specific therapeutic and prophylactic interventions available for prion diseases, thus active surveillance of human prion diseases is critical for disease control and prevention. Since 1993, CJD surveillance systems have been established in many countries and regions, and several long-term multinational cooperative projects have been conducted.In this paper, the epidemiological characteristics of various human prion diseases and the active surveillance systems pertaining to them in different countries and regions are summarized and reviewed. PMID- 27251307 TI - Molecular Design of Benzodithiophene-Based Organic Photovoltaic Materials. AB - Advances in the design and application of highly efficient conjugated polymers and small molecules over the past years have enabled the rapid progress in the development of organic photovoltaic (OPV) technology as a promising alternative to conventional solar cells. Among the numerous OPV materials, benzodithiophene (BDT)-based polymers and small molecules have come to the fore in achieving outstanding power conversion efficiency (PCE) and breaking 10% efficiency barrier in the single junction OPV devices. Remarkably, the OPV device featured by BDT based polymer has recently demonstrated an impressive PCE of 11.21%, indicating the great potential of this class of materials in commercial photovoltaic applications. In this review, we offered an overview of the organic photovoltaic materials based on BDT from the aspects of backbones, functional groups, alkyl chains, and device performance, trying to provide a guideline about the structure performance relationship. We believe more exciting BDT-based photovoltaic materials and devices will be developed in the near future. PMID- 27251306 TI - TLR9-ERK-mTOR signaling is critical for autophagic cell death induced by CpG oligodeoxynucleotide 107 combined with irradiation in glioma cells. AB - Synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) function as potential radiosensitizers for glioma treatment, although the underlying mechanism is unclear. It was observed that CpG ODN107, when combined with irradiation, did not induce apoptosis. Herein, the effect of CpG ODN107 + irradiation on autophagy and the related signaling pathways was investigated. In vitro, CpG ODN107 + irradiation induced autophagosome formation, increased the ratio of LC3 II/LC3 I, beclin 1 and decreased p62 expression in U87 cells. Meanwhile, CpG ODN107 also increased LC3 II/LC3 I expression in U251 and CHG-5 cells. In vivo, CpG ODN107 combined with local radiotherapy induced autophagosome formation in orthotopic transplantation tumor. Investigation of the molecular mechanisms demonstrated that CpG ODN107 + irradiation increased the levels of TLR9 and p-ERK, and decreased the level of p-mTOR in glioma cells. Further, TLR9 specific siRNA could affect the expressions of p-ERK and autophagy-related proteins in glioma cells. Taken together, CpG ODN107 combined with irradiation could induce autophagic cell death, and this effect was closely related to the TLR9-ERK-mTOR signaling pathway in glioma cells, providing new insights into the investigation mechanism of CpG ODN. PMID- 27251308 TI - C-peptide antioxidant adaptive pathways in beta cells and diabetes. AB - In this review, we present findings that support autocrine cell protection by C peptide in the context of clinical studies of type 1 diabetes (T1D), which universally measure C-peptide serum levels as a surrogate for beta cell functional mass. Over the last decade, evidence has accumulated that supports models in which C-peptide, cosecreted with insulin by pancreatic beta cells, acts on peripheral targets including the vascular endothelium to reduce oxidative stress and apoptosis subsequent to exposure to diabetic insults. In parallel, as assays have become more sensitive, C-peptide has been detected in the circulation of most subjects with T1D where higher C-peptide levels are associated with fewer and slower development of diabetic microvascular complications, consistent with antioxidant protection by C-peptide. Clinical trials investigating C-peptide replacement therapy effects have demonstrated amelioration of T1D nephropathy and neuropathy. Recently, the antioxidant action of C-peptide was extended to the beta cells secreting it, that is an autocrine mechanism. Autocrine protection has major implications for the treatment of diabetes because the more C-peptide secreted, the more protection provided to the same beta cells resulting in a slower decay in beta cell functional mass over the time course of disease. Why beta cells evolved to cosecrete an antioxidant C-peptide hormone together with the glycaemia-lowering insulin hormone is explored in the context of proposed evolutionary advantages of physiologically transient oxidative stress and insulin resistance as an adaptation for survival through times of fuel scarcity. The importance of recognizing autocrine C-peptide protection of functional beta cell mass in observational clinical studies, and its therapeutic implications in interventional C-peptide-replacement studies, will be discussed. PMID- 27251309 TI - EU agrees tighter standards for medical devices. PMID- 27251310 TI - Diagnostic accuracy of two point-of-care kits for the diagnosis of Giardia species infection in dogs. AB - OBJECTIVES: The objective of this study was to compare results obtained by ZnSO4 Flotation and SNAP ((r)) Giardia to those generated by the new point-of-care tests Single and Triple Rapid. METHODS: Prospective study evaluating 51 canine faecal samples submitted at a reference laboratory for the presence of Giardia spp. Kappa statistics, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were calculated by comparing the new tests to the combined results of ZnSO4 and SNAP tests. RESULTS: There was fair (Single Rapid, j=0.434) to good (Triple Rapid, j =0.797) agreement with the reference tests. At this study's prevalence (59 to 61%), specificities and PPV were high (1.00) with both Rapid tests, but sensitivities and NPV were lower for the Single than for the Triple (0.48 vs 0.83 and 0.55 vs 0.80) tests. At lower prevalence rates, both tests exhibited a high PPV (1.00), but the NPV were higher with the Triple (0.96 to 0.99) than the Single (0.88 to 0.96) Rapid test. CLINICAL SIGNIFICANCE: Both tests exhibited excellent PPV values at all prevalence rates but an excellent NPV only at low prevalence. As the prevalence is likely to be low (<15%) in clinical settings, we propose that these tests may be helpful in the in-house diagnosis of Giardia spp infection. However, they exhibit lower sensitivity than the combined sensitivity of ZnSO4 and SNAP tests, particularly in high prevalence settings. PMID- 27251311 TI - Response to the letter. PMID- 27251312 TI - Advances in Neonatal Pulmonary Hypertension. AB - Persistent pulmonary hypertension of the newborn (PPHN) is a surprisingly common event in the neonatal intensive care unit, and affects both term and preterm infants. Recent studies have begun to elucidate the maternal, fetal and genetic risk factors that trigger PPHN. There have been numerous therapeutic advances over the last decade. It is now appreciated that oxygen supplementation, particularly for the goal of pulmonary vasodilation, needs to be approached as a therapy that has risks and benefits. Administration of surfactant or inhaled nitric oxide (iNO) therapy at a lower acuity of illness can decrease the risk of extracorporeal membrane oxygenation/death, progression of disease and duration of hospital stay. Milrinone may have specific benefits as an 'inodilator', as prolonged exposure to iNO plus oxygen may activate phosphodiesterase (PDE) 3A. Additionally, sildenafil and hydrocortisone may benefit infants exposed to hyperoxia and oxidative stress. Continued investigation is likely to reveal new therapies such as citrulline and cinaciguat that will enhance NO synthase and soluble guanylate cyclase function. Continued laboratory and clinical investigation will be needed to optimize treatment and improve outcomes. PMID- 27251313 TI - Feasibility and Performance Test of a Real-Time Sensor-Informed Context-Sensitive Ecological Momentary Assessment to Capture Physical Activity. AB - BACKGROUND: Objective physical activity monitors (eg, accelerometers) have high rates of nonwear and do not provide contextual information about behavior. OBJECTIVE: This study tested performance and value of a mobile phone app that combined objective and real-time self-report methods to measure physical activity using sensor-informed context-sensitive ecological momentary assessment (CS-EMA). METHODS: The app was programmed to prompt CS-EMA surveys immediately after 3 types of events detected by the mobile phone's built-in motion sensor: (1) Activity (ie, mobile phone movement), (2) No-Activity (ie, mobile phone nonmovement), and (3) No-Data (ie, mobile phone or app powered off). In addition, the app triggered random (ie, signal-contingent) ecological momentary assessment (R-EMA) prompts (up to 7 per day). A sample of 39 ethnically diverse high school students in the United States (aged 14-18, 54% female) tested the app over 14 continuous days during nonschool time. Both CS-EMA and R-EMA prompts assessed activity type (eg, reading or doing homework, eating or drinking, sports or exercising) and contextual characteristics of the activity (eg, location, social company, purpose). Activity was also measured with a waist-worn Actigraph accelerometer. RESULTS: The average CS-EMA + R-EMA prompt compliance and survey completion rates were 80.5% and 98.5%, respectively. More moderate-to-vigorous intensity physical activity was recorded by the waist-worn accelerometer in the 30 minutes before CS-EMA activity prompts (M=5.84 minutes) than CS-EMA No Activity (M=1.11 minutes) and CS-EMA No-Data (M=0.76 minute) prompts (P's<.001). Participants were almost 5 times as likely to report going somewhere (ie, active or motorized transit) in the 30 minutes before CS-EMA Activity than R-EMA prompts (odds ratio=4.91, 95% confidence interval=2.16-11.12). CONCLUSIONS: Mobile phone apps using motion sensor-informed CS-EMA are acceptable among high school students and may be used to augment objective physical activity data collected from traditional waist-worn accelerometers. PMID- 27251315 TI - Most Accessed Papers: An Interesting Mix. PMID- 27251314 TI - Characterization of Motor and Somatosensory Evoked Potentials in the Yucatan Micropig Using Transcranial and Epidural Stimulation. AB - Yucatan micropigs have brain and spinal cord dimensions similar to humans and are useful for certain spinal cord injury (SCI) translational studies. Micropigs are readily trained in behavioral tasks, allowing consistent testing of locomotor loss and recovery. However, there has been little description of their motor and sensory pathway neurophysiology. We established methods to assess motor and sensory cortical evoked potentials in the anesthetized, uninjured state. We also evaluated epidurally evoked motor and sensory stimuli from the T6 and T9 levels, spanning the intended contusion injury epicenter. Response detection frequency, mean latency and amplitude values, and variability of evoked potentials were determined. Somatosensory evoked potentials were reliable and best detected during stimulation of peripheral nerve and epidural stimulation by referencing the lateral cortex to midline Fz. The most reliable hindlimb motor evoked potential (MEP) occurred in tibialis anterior. We found MEPs in forelimb muscles in response to thoracic epidural stimulation likely generated from propriospinal pathways. Cranially stimulated MEPs were easier to evoke in the upper limbs than in the hindlimbs. Autopsy studies revealed substantial variations in cortical morphology between animals. This electrophysiological study establishes that neurophysiological measures can be reliably obtained in micropigs in a time frame compatible with other experimental procedures, such as SCI and transplantation. It underscores the need to better understand the motor control pathways, including the corticospinal tract, to determine which therapeutics are suitable for testing in the pig model. PMID- 27251316 TI - Polyclonality of Trichophyton rubrum Isolates in aDermatophytosis Patient with Multiple Lesions. AB - We cultured 15 isolates of Trichophyton rubrum and one isolate of Trichophyton mentagrophytes from an 82-year-old male tinea patient with multiple lesions. To determine whether feet lesions were the source of dermatophytes of other tinea lesions, we extracted total cellular DNA from the T. rubrum isolates(13 from feet, two from right waist and buttock). PCR targeting the non-transcribed spacer(NTS)region of ribosomal RNA gene was performed. Molecular polymorphisms were detected by length variation of amplicons.Four molecular types were found among the 15 isolates. The predominant type, which we previously named Type III, comprised seven isolates cultured from both feet and from left waist and buttock. This was followed by Type VI, five isolates; Type V, two isolates; and Type IV, one isolate. Apart from type III, which was cultured from both feet, isolates were cultured from one foot only. The patient was successfully treated for all types with a six-month course of oral terbinafine and topical luliconazole. The molecular typing supported the notion that tinea pedis was the source of tinea corporis in the patient. PMID- 27251317 TI - A Case of Fingernail Onychomycosis due to Aspergillus flavus. AB - A 56-year-old woman on insulin therapy for diabetes visited our clinic due to whitish discoloration on the right index finger. Despite topical application of 1% lanoconazole solution, the lesion grew, causing paronychia. Direct microscopy revealed non-dermatophyte molds. Based on the morphological features and genetic analysis of the isolate, the pathogen was identified as Aspergillus flavus. The patient was diagnosed with proximal subungual onychomycosis due to A. flavus. Following itraconazole pulse therapy, she was cured in 6 months. To our knowledge, this is the first reported case of fingernail onychomycosis due to A. flavus in Japan. PMID- 27251318 TI - A Case of Cutaneous Fusariosis of the Scrotum as a Complication of Acute Myeloid Leukemia. AB - Fusarium, a hyphomyocetous fungus, is often isolated from the environment as a laboratory contaminant, but is also known as a pathogen causing keratomycosis, onychomycosis, and opportunistic infection of the skin and viscera. We report a 67-year-old man with localized cutaneous fusariosis of the scrotum, as a complication of acute myeloid leukemia (AML) under chemotherapy. An induration of 25 mm in diameter, which was covered by necrosis and black crust and with pain upon pressure, was found on the scrotum. Direct microscopic examination of the necrosis showed numerous fungal elements. Culture on Sabouraud dextrose agar with cycloheximide yielded a floccose, grayish white colony. Microscopically, crescent shaped macroconidia and oval microconidia were abundant. The fungus was identified using gene analysis as Fusarium falciforme of the Fusarium solani species complex. The lesion was treated by voriconazole (total dose: 66,180 mg) and was reduced to 15 mm in diameter. Other metastatic lesions did not appear. After 4 months from the first visit to our department, the patient died of AML. It is believed that the treatment in the early stage of infection prevented further extension of the lesion. During examination of necrotic lesions occurring on the skin of patients with hematological malignancies, it is important to include mycological examination for opportunistic fungal infections, such as aspergillosis or fusariosis, which are easily overlooked by routine culture methods using conventional media with cycloheximide. This paper summarizes cases of cutaneous fusariosis in Japan. PMID- 27251319 TI - Oral Antifungal Drugs in the Treatment of Dermatomycosis. AB - Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis. PMID- 27251320 TI - Invasive Aspergillosis in Hematological Patients. AB - Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and beta-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases. PMID- 27251321 TI - Cutaneous Mycoses: Management and Education in Universities and Their Clinics in Japan. AB - In May 2015, information on the current status of mycological examinations in university clinics, and the education of students, and junior and senior residents in Japanese universities was gathered using a questionnaire, which was completed by 98 of the 117 (83.8%) professors or directors in charge of dermatology departments in Japan that were included in the survey.The questionnaire items were divided into three parts; namely, Part A, inspection methods used for diagnosis of cutaneous mycoses in each university clinic; Part B, need for a network and construction of a support system for medical care and education; and Part C, status of education of undergraduate students and residents. Some of these questions are based on a similar survey in 2007. In Part A, it was found that only 3% of university clinics performed fungal culture for all or most cases, indicating a drop from the previous study (9% in 2007). Meanwhile, responses indicating that fungal culture was almost or completely done away with accounted for about 36%. Based on type of mycoses, fungal culture for deep mycoses was performed in about 83% of the facilities. However, the percentage for superficial mycoses was very low, wherein only 39% of the facilities performed cultures even for tinea capitis. Trichophyton tonsurans infection was "often" or "sometimes" diagnosed in 22% of the facilities, with the other 78% reporting "no" or "almost no cases" of T. tonsurans infection diagnosed. In Part B, it was found that 96% of respondents (up from 89% in 2007) desired help from the university network, including aid in identifying fungal isolates, diagnosing rare fungal infections, and basic training in medical mycology of young doctors (senior residents in university hospitals). In Part C, it was found that education in direct KOH preparation for senior residents was satisfactory in about 80% of the facilities. However, about 45% of respondents reported that majority or all of the senior residents in their institutes had no opportunity to perform fungal culture. The results indicate that respondents desire a diagnostic laboratory for medical mycology, especially for rare (deep) mycoses, and a database for diagnosis and management of deep mycoses. It is still therefore necessary to continue an educational program targeted at leaders to educate those in charge of each department. PMID- 27251322 TI - Term 10. PMID- 27251323 TI - KI-catalyzed alpha-acyloxylation of acetone with carboxylic acids. AB - The KI-catalyzed reaction of acetone with aromatic carboxylic acids is achieved, leading to alpha-acyloxycarbonyl compounds in good to excellent yields under mild reaction conditions. The present method exhibits good functional-group compatibility. Notably, this reaction system is even suitable for cinnamic acid, 3-phenylpropiolic acid and 4-phenylbutanoic acid. A kinetic isotope effect (KIE) study indicates that C-H cleavage of the acetone is the rate-limiting step in the catalytic cycle. PMID- 27251324 TI - Effect of Oxidation Condition on Growth of N: ZnO Prepared by Oxidizing Sputtering Zn-N Film. AB - Nitrogen-doped zinc oxide (N: ZnO) films have been prepared by oxidizing reactive RF magnetron-sputtering zinc nitride (Zn-N) films. The effect of oxidation temperature and oxidation time on the growth, transmittance, and electrical properties of the film has been explored. The results show that both long oxidation time and high oxidation temperature can obtain the film with a good transmittance (over 80 % for visible and infrared light) and a high carrier concentration. The N: ZnO film exhibits a special growth model with the oxidation time and is first to form a N: ZnO particle on the surface, then to become a N: ZnO layer, and followed by the inside Zn-N segregating to the surface to oxidize N: ZnO. The surface particle oxidized more adequately than the inside. However, the X-ray photoemission spectroscopy results show that the lower N concentration results in the lower N substitution in the O lattice (No). This leads to the formation of n-type N: ZnO and the decrease of carrier concentration. Thus, this method can be used to tune the microstructure, optical transmittance, and electrical properties of the N: ZnO film. PMID- 27251325 TI - Mechanisms of Low-Temperature Nitridation Technology on a TaN Thin Film Resistor for Temperature Sensor Applications. AB - In this letter, we propose a novel low-temperature nitridation technology on a tantalum nitride (TaN) thin film resistor (TFR) through supercritical carbon dioxide (SCCO2) treatment for temperature sensor applications. We also found that the sensitivity of temperature of the TaN TFR was improved about 10.2 %, which can be demonstrated from measurement of temperature coefficient of resistance (TCR). In order to understand the mechanism of SCCO2 nitridation on the TaN TFR, the carrier conduction mechanism of the device was analyzed through current fitting. The current conduction mechanism of the TaN TFR changes from hopping to a Schottky emission after the low-temperature SCCO2 nitridation treatment. A model of vacancy passivation in TaN grains with nitrogen and by SCCO2 nitridation treatment is eventually proposed to increase the isolation ability in TaN TFR, which causes the transfer of current conduction mechanisms. PMID- 27251326 TI - Green Synthesis of Magnetite (Fe3O4) Nanoparticles Using Seaweed (Kappaphycus alvarezii) Extract. AB - In this study, a simple, rapid, and eco-friendly green method was introduced to synthesize magnetite nanoparticles (Fe3O4-NPs) successfully. Seaweed Kappaphycus alvarezii (K. alvarezii) was employed as a green reducing and stabilizing agents. The synthesized Fe3O4-NPs were characterized with X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared (FT-IR), and transmission electron microscopy (TEM) techniques. The X-ray diffraction planes at (220), (311), (400), (422), (511), (440), and (533) were corresponding to the standard Fe3O4 patterns, which showed the high purity and crystallinity of Fe3O4-NPs had been synthesized. Based on FT-IR analysis, two characteristic absorption peaks were observed at 556 and 423 cm(-1), which proved the existence of Fe3O4 in the prepared nanoparticles. TEM image displayed the synthesized Fe3O4 NPs were mostly in spherical shape with an average size of 14.7 nm. PMID- 27251327 TI - Overexpression of a Chimeric Gene, OsDST-SRDX, Improved Salt Tolerance of Perennial Ryegrass. AB - The Drought and Salt Tolerance gene (DST) encodes a C2H2 zinc finger transcription factor, which negatively regulates salt tolerance in rice (Oryza sativa). Phylogenetic analysis of six homologues of DST genes in different plant species revealed that DST genes were conserved evolutionarily. Here, the rice DST gene was linked to an SRDX domain for gene expression repression based on the Chimeric REpressor gene-Silencing Technology (CRES-T) to make a chimeric gene (OsDST-SRDX) construct and introduced into perennial ryegrass by Agrobacterium mediated transformation. Integration and expression of the OsDST-SRDX in transgenic plants were tested by PCR and RT-PCR, respectively. Transgenic lines overexpressing the OsDST-SRDX fusion gene showed obvious phenotypic differences and clear resistance to salt-shock and to continuous salt stresses compared to non-transgenic plants. Physiological analyses including relative leaf water content, electrolyte leakage, proline content, malondialdehyde (MDA) content, H2O2 content and sodium and potassium accumulation indicated that the OsDST-SRDX fusion gene enhanced salt tolerance in transgenic perennial ryegrass by altering a wide range of physiological responses. To our best knowledge this study is the first report of utilizing Chimeric Repressor gene-Silencing Technology (CRES-T) in turfgrass and forage species for salt-tolerance improvement. PMID- 27251329 TI - Exploring the diffusion of tweets designed to raise the road safety agenda in Saudi Arabia. AB - This study demonstrates the importance of understanding the diffusion process in social media such as Twitter as an example of the relationship between new media platforms and health promotion interventions. Evidence-informed tweets were developed, pilot tested and distributed to all followers of the Ministry of Health's Twitter account with the aim of influencing the agenda on road safety in Saudi Arabia. The dissemination pattern and influence of this health communication was assessed. We collected 70 tweets into two groups (29 intervention tweets and 41 additional supported tweets) extracted from the Tweetreach data set and then analysed them using Microsoft Excel and SPSS. Using the concept of innovation/imitation as defined in the Bass Model, we classified retweeting by direct followers as innovation and retweeting by users who were not followers as imitation. In the study, we identify an informative indicator of successful diffusion and propose a novel procedure to measure innovation/imitation coefficients ( p and q). We also provided a statistical procedure for evaluating tweet adoption by innovators (influentials) and imitators. In addition, we also assessed the use of message design tools for new media messages. The resulting information can be used to improve public health and health promotion interventions at the levels of planning, design, implementation and evaluation. PMID- 27251328 TI - Erratum to: Controlling the response to DNA damage by the APC/C-Cdh1. PMID- 27251330 TI - Impact of Distal Protection with Filter-Type Device on Long-term Outcome after Percutaneous Coronary Intervention for Acute Myocardial Infarction: Clinical Results with Filtrap(r). AB - AIM: Although distal embolization during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) deteriorates cardiac function, whether distal protection (DP) can improve prognosis is still controversial. We investigated whether a filter-type DP device, Filtrap(r), could improve long-term outcomes after PCI for AMI. METHOD: We studied 164 patients (130 men, mean age: 65.7 years) who underwent PCI. Patients were divided into two groups based on the use of Filtrap(r). The occurrence of congestive heart failure (CHF) and major adverse cardiac events (MACE) defined as cardiac death, recurrent AMI, and target vessel revascularization were compared. RESULT: Between DP (n=53, 41 men, mean age: 65.5 years) and non-DP (n=111, 89 men, mean age: 65.8 years) groups, although there was significantly greater plaque area in the DP group than in the non-DP group, there were no significant differences in coronary reperfusion flow after PCI. Interestingly, patients with CHF in the non-DP group exhibited a higher CK level than those in the DP group. During a 2-year follow-up period, cumulative CHF was significantly lower in the DP group than in the non-DP group (log-rank p=0.018), and there was no significant difference in the MACE rate (log rank p=0.238). The use of DP device could not predict MACE, but could predict CHF by multivariate analysis (odds ratio=0.099, 95% CI: 0.02-0.42, p=0.005). CONCLUSION: These results demonstrate that favorable clinical outcomes could be achieved by the filter-type DP device in AMI, particularly in patients with CHF. PMID- 27251331 TI - [Freiburg keratoconus registry : Example of application of smart data for clinical research and inititial results]. AB - BACKGROUND: Keratoconus is a progressive corneal disease with thinning and scarring of the cornea. Diagnostic and treatment options are usually evaluated in large prospective or retrospective trials. Big data and smart data provide the possibility to analyze routine data for clinical research. In this article we report the generation of a monocentric keratoconus registry by means of computerized data analysis of routine data. This demonstrates the potential of clinical research by means of routine data. METHODS: A "clinical data warehouse" was created from all available routine electronic data. At the time of first presentation, each eye was classified into one out of four categories: suspected, early disease, late disease and status postkeratoplasty. Through integration of multiple data sources the clinical course for each patient was documented in the registry. RESULTS: A total of 3681 eyes from 1841 patients were included. The median follow-up time was 0.54 years. Patient age was higher in the groups with more severe stages of keratoconus, the proportion of female patients was higher in the group of suspected keratoconus and patient age and male to female ratios showed statistically significant differences between the groups (p < 0.001). CONCLUSION: We were able to create a "clinical data warehouse" by linking multiple data sources and normalizing the data. With this tool we established a novel, monocentric keratoconus registry. Only the grading of disease severity and the exclusion of false positive results were carried out manually. In our opinion establishing a structured clinical data warehouse has a huge potential for clinical and retrospective studies and proves the value of the Smart Data concept. PMID- 27251332 TI - [Unilateral conjunctival chemosis with edematous facial involvement]. PMID- 27251333 TI - [Smart data : Possibilities for clinical research and translation into practice]. PMID- 27251334 TI - Current Approaches to Tactical Performance Analyses in Soccer Using Position Data. AB - Tactical match performance depends on the quality of actions of individual players or teams in space and time during match-play in order to be successful. Technological innovations have led to new possibilities to capture accurate spatio-temporal information of all players and unravel the dynamics and complexity of soccer matches. The main aim of this article is to give an overview of the current state of development of the analysis of position data in soccer. Based on the same single set of position data of a high-level 11 versus 11 match (Bayern Munich against FC Barcelona) three different promising approaches from the perspective of dynamic systems and neural networks will be presented: Tactical performance analysis revealed inter-player coordination, inter-team and inter-line coordination before critical events, as well as team-team interaction and compactness coefficients. This could lead to a multi-disciplinary discussion on match analyses in sport science and new avenues for theoretical and practical implications in soccer. PMID- 27251335 TI - Identification and characteristics of patients with palliative care needs in Brazilian primary care. AB - BACKGROUND: The Brazilian healthcare system offers universal coverage but lacks information about how patients with PC needs are serviced by its primary care program, Estrategia Saude da Familia (ESF). METHODS: Cross-sectional study in community settings. Patients in ESF program were screened using a Palliative Care Screening Tool (PCST). Included patients were assessed with Karnofsky Performance Scale (KPS), Edmonton Symptom Assessment System (ESAS) and Palliative Care Outcome Scale (POS). RESULTS: Patients with PC needs are accessing the ESF program regardless of there being no specific PC support provided. From 238 patients identified, 73 (43 women, 30 men) were identified as having a need for PC, and the mean age was 77.18 (95 % Confidence Interval = +/-2,78) years, with non-malignant neurologic conditions, such as dementia and cerebrovascular diseases, being the most common (53 % of all patients). Chronic conditions (2 or more years) were found in 70 % of these patients, with 71 % scoring 50 or less points in the KPS. Overall symptom intensity was low, with the exception of some cases with moderate and high score, and POS average score was 14.16 points (minimum = 4; maximum = 28). Most patients received medication and professional support through the primary care units, but limitations of services were identified, including lack of home visits and limited multi-professional approaches. CONCLUSION: Patients with PC needs were identified in ESF program. Basic health care support is provided but there is a lack of attention to some specific needs. PC policies and professional training should be implemented to improve this area. PMID- 27251337 TI - Antipsychotics for fibromyalgia in adults. AB - BACKGROUND: This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms. OBJECTIVES: To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults. SEARCH METHODS: We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors. SELECTION CRITERIA: We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults. DATA COLLECTION AND ANALYSIS: We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included a total of four studies with 296 participants.Three studies with 206 participants compared quetiapine, an atypical (second-generation) antipsychotic, with placebo. One study used a cross-over design and two studies a parallel-group design. Study duration was eight or 12 weeks. Quetiapine was used in all studies with a bedtime dosage between 50 and 300 mg/day. All studies had one or more sources of potential major bias and we judged them to be at moderate risk of bias overall. The primary outcomes in this review were participant-reported pain relief of 50% or greater, Patient Global Impression of Change (PGIC) much or very much improved, withdrawal due to adverse events (tolerability) and serious adverse events (safety).Second tier evidence indicated that quetiapine was not statistically superior to placebo in the number of participants with a 50% or more pain reduction (very low quality evidence). No study reported data on PGIC. A greater proportion of participants on quetiapine reported a 30% or more pain reduction (risk difference (RD) 0.12, 95% confidence interval (CI) 0.00 to 0.23; number needed to treat for an additional benefit (NNTB) 8, 95% CI 5 to 100) (very low quality evidence). A greater proportion of participants on quetiapine reported a clinically relevant improvement of health related quality of life compared to placebo ( RD 0.18, 95% CI 0.05 to 0.31; NNTB 5, 95% CI 3 to 20) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing sleep problems (standardised mean difference (SMD) -0.67, 95% CI -1.10 to -0.23), depression (SMD -0.39, 95% CI -0.74 to 0.04) and anxiety (SMD -0.40, 95% CI -0.69 to -0.11) (very low quality evidence). Quetiapine was statistically superior to placebo in reducing the risk of withdrawing from the study due to a lack of efficacy (RD -0.14, 95% CI -0.23 to 0.05) (very low quality evidence). There was no statistically significant difference between quetiapine and placebo in the proportion of participants withdrawing due to adverse events (tolerability) (very low quality evidence), in the frequency of serious adverse events (safety) (very low quality evidence) and in the proportion of participants reporting dizziness and somnolence as an adverse event (very low quality evidence). In more participants in the quetiapine group a substantial weight gain was noted (RD 0.08, 95% CI 0.02 to 0.15; number needed to treat for an additional harm (NNTH) 12, 95% CI 6 to 50) (very low quality evidence). We downgraded the quality of evidence by three levels to a very low quality rating because of limitations of study design, indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed).One parallel design study with 90 participants compared quetiapine (50 to 300 mg/day flexible at bedtime) to amitriptyline (10 to 75 mg/day flexible at bedtime). The study had three major risks of bias and we judged it to be at moderate risk of bias overall. We downgraded the quality of evidence by two levels to a low quality rating because of indirectness (patients with major medical diseases and mental disorders were excluded) and imprecision (fewer than 400 patients were analysed). Third tier evidence indicated no statistically significant differences between the two drugs. Both drugs did not statistically significantly differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life and in the proportion of participants reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared to amitriptyline, more participants left the study due to adverse events (low quality evidence). No serious adverse events were reported (low quality evidence).We found no relevant study with other antipsychotics than quetiapine in fibromyalgia. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that quetiapine may be considered for a time-limited trial (4 to 12 weeks) to reduce pain, sleep problems, depression and anxiety in fibromyalgia patients with major depression. Potential side effects such as weight gain should be balanced against the potential benefits in shared decision making with the patient. PMID- 27251336 TI - Neuro-Mechanics of Recumbent Leg Cycling in Post-Acute Stroke Patients. AB - Cycling training is strongly applied in post-stroke rehabilitation, but how its modular control is altered soon after stroke has been not analyzed yet. EMG signals from 9 leg muscles and pedal forces were measured bilaterally during recumbent pedaling in 16 post-acute stroke patients and 12 age-matched healthy controls. Patients were asked to walk over a GaitRite mat and standard gait parameters were computed. Four muscle synergies were extracted through nonnegative matrix factorization in healthy subjects and patients unaffected legs. Two to four synergies were identified in the affected sides and the number of synergies significantly correlated with the Motricity Index (Spearman's coefficient = 0.521). The reduced coordination complexity resulted in a reduced biomechanical performance, with the two-module sub-group showing the lowest work production and mechanical effectiveness in the affected side. These patients also exhibited locomotor impairments (reduced gait speed, asymmetrical stance time, prolonged double support time). Significant correlations were found between cycling-based metrics and gait parameters, suggesting that neuro-mechanical quantities of pedaling can inform on walking dysfunctions. Our findings support the use of pedaling as a rehabilitation method and an assessment tool after stroke, mainly in the early phase, when patients can be unable to perform a safe and active gait training. PMID- 27251338 TI - Burnout and health behaviors in health professionals from seven European countries. AB - OBJECTIVES: Within an underlying health-impairing process, work stressors exhaust employees' mental and physical resources and lead to exhaustion/burnout and to health problems, with health-impairing behaviors being one of the potential mechanisms, linking burnout to ill health. The study aims to explore the associations between burnout and fast food consumption, exercise, alcohol consumption and painkiller use in a multinational sample of 2623 doctors, nurses and residents from Greece, Portugal, Bulgaria, Romania, Turkey, Croatia and Macedonia, adopting a cross-national approach. METHODS: Data are part of the international cross-sectional quantitative ORCAB survey. The measures included the Maslach Burnout Inventory and the Health Behaviors Questionnaire. RESULTS: Burnout was significantly positively associated with higher fast food consumption, infrequent exercise, higher alcohol consumption and more frequent painkiller use in the full sample, and these associations remained significant after the inclusion of individual differences factors and country of residence. Cross-national comparisons showed significant differences in burnout and health behaviors, and some differences in the statistical significance and magnitude (but not the direction) of the associations between them. Health professionals from Turkey, Greece and Bulgaria reported the most unfavorable experiences. CONCLUSIONS: Burnout and risk health behaviors among health professionals are important both in the context of health professionals' health and well-being and as factors contributing to medical errors and inadequate patient safety. Organizational interventions should incorporate early identification of such behaviors together with programs promoting health and aimed at the reduction of burnout and work-related stress. PMID- 27251339 TI - Childhood Risk Factors and Pregnancy-Induced Hypertension: The Bogalusa Heart Study. AB - BACKGROUND: Pregnancy-induced hypertension (PIH) causes increased risk of maternal, fetal, and neonatal morbidity and mortality. Identification of risk factors for PIH in early life is central to the development of prevention strategies. METHODS: A cohort of 703 women aged 25.5-51.3 years from the Bogalusa Heart Study were included. PIH were defined as self-reported hypertension during pregnancy and a blood pressure level <140/90mm Hg without antihypertensive medication (n = 131) at the subsequent examinations. Body mass index (BMI), systolic and diastolic blood pressure, high- and low-density lipoprotein cholesterol, and triglycerides measured during childhood (4-17 years) were considered. General linear models were used to examine differences in childhood between those who did and those who did not develop PIH. Logistic regression models were used to estimate odds ratios for PIH associated with childhood risk factors. RESULTS: Compared to women who did not develop PIH, those who developed PIH had higher BMI (20.2 vs. 19.2kg/m(2), P = 0.0002) and systolic blood pressure (104.1 vs. 103.3mm Hg, P = 0.008) in childhood. After adjustment for other variables, childhood BMI was the only risk factor associated with PIH, with each standard deviation increase in childhood BMI being associated with an odds ratio of 1.35 (95% confidence interval: 1.08-1.68) for PIH. The odds of PIH increased significantly as childhood BMI increased from the bottom quartile to the top quartile (P for trend = 0.006). CONCLUSIONS: Elevated childhood BMI is a significant risk factor for PIH in adulthood, which underscores the importance of body weight control in childhood for prevention of PIH. PMID- 27251340 TI - Clinicopathologic features of IgA nephropathy patients with different levels of proteinuria. AB - AIMS: To investigate the clinicopathologic features of IgA nephropathy (IgAN) patients with different levels of proteinuria and its clinical significance. METHODS: This was a single-center retrospective cohort study. Patients with biopsy-proven primary IgAN were enrolled from January 2006 to December 2011 in The First Affiliated Hospital of Sun Yat-sen University, divided into six groups based on proteinuria at biopsy (<= 0.30 g/d, 0.31 - 0.50 g/d, 0.51 - 1.00 g/d, 1.01 - 2.00 g/d, 2.01 - 3.00 g/d, and > 3.00 g/d). Demographic and clinicopathologic data were collected and analyzed. RESULTS: 1,413 patients were enrolled in this study, with the median proteinuria being 0.61 g/d (interquartile range 0.30 - 1.29). Patients with proteinuria > 0.50 g/d showed significant differences in their clinicopathologic characteristics with higher prevalence of hypertension, hypoalbuminemia, hyperuricemia, hypercholesterolemia and hypertriglyceridemia, worse renal function, higher proportions of segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and interstitial inflammation. Even the patients with proteinuria 0.31 - 0.50 g/d exhibited higher uric acid, lower total serum protein and albumin, higher proportions of crescents, and global glomerulosclerosis. Furthermore, multiple risk factors linear regression analysis has shown that there were significant associations between proteinuria and serum albumin, uric acid, total cholesterol, triglyceride, systolic blood pressure, degrees of segmental glomerulosclerosis, proportions of crescents, and global glomerulosclerosis. CONCLUSION: Clinicopathologic features were significantly worse in IgAN patients with increasing of proteinuria. PMID- 27251341 TI - Fluconazole dosing predictions in critically-ill patients receiving prolonged intermittent renal replacement therapy: a Monte Carlo simulation approach. AB - Fluconazole is a renally-eliminated antifungal commonly used to treat Candida species infections. In critically-ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic (PK) data are available to guide fluconazole dosing. We used previously-published fluconazole clearance data and PK data of critically-ill patients with acute kidney injury to develop a PK model with the goal of determining a therapeutic dosing regimen for critically-ill patients receiving PIRRT. Monte Carlo simulations were performed to create a virtual cohort of patients receiving different fluconazole dosing regimens. Plasma drug concentration-time profiles were evaluated on the probability of attaining a mean 24-hour area under the drug concentration-time curve to minimum inhibitory concentration ratio (AUC24h : MIC) of 100 during the initial 48 hours of antifungal therapy. At the susceptibility breakpoint of Candida albicans (2 mg/L), 93 - 96% of simulated subjects receiving PIRRT attained the pharmacodynamic target with a fluconazole 800-mg loading dose plus 400 mg twice daily (q12h or pre and post PIRRT) regimen. Monte Carlo simulations of a PK model of PIRRT provided a basis for the development of an informed fluconazole dosing recommendation when PK data was limited. This finding should be validated in the clinical setting. PMID- 27251342 TI - Cononsolvency behavior of hydrophobes in water + methanol mixtures. AB - The molecular origin of cononsolvency behavior is explored using molecular dynamics simulations. Cononsolvency behavior in aggregations of methane molecules and conformational changes of those clusters dissolved in water + methanol mixtures are confirmed by re-entrant changes in the solvent-mediated interactions with increasing methanol concentration. The results indicate that the cononsolvency behavior arises from the solute-solute hydrophobic interactions rather than other interactions such as solute-solvent hydrophilic interactions. Furthermore, we show that even the van der Waals interaction is not necessary to induce the cononsolvency behavior by investigating the dimerization process of repulsive cavities. The non-monotonic change of the solvent-mediated interaction results from the difference in the concentration dependencies of excess chemical potentials between an isolated methane and methane clusters. The concentration dependencies of the excess chemical potentials are decomposed into contributions from various intermolecular effective interactions through the framework of the Kirkwood-Buff theory, and then we show that the change of the relative magnitude between hydrophobe-methanol and hydrophobe-water effective interactions with increasing methanol concentration is responsible for the cononsolvency behavior. PMID- 27251343 TI - Moving Toward 21st-Century Clinical Licensure Examinations in Dentistry. PMID- 27251344 TI - The Buffalo Model: Shifting the Focus of Clinical Licensure Exams in Dentistry to Address Ethical Concerns Regarding Patient Care. AB - Most jurisdictions grant dental licensure to graduating students following successful completion of a clinical exam. Testing agencies, which are independent of dental schools, nevertheless conduct their exams at school facilities. Patient participation in these exams raises ethical concerns regarding such issues as unlicensed providers' performing irreversible procedures with minimal supervision and graduates' limited accessibility to provide follow-up treatment. To address these concerns, a collaborative effort between University at Buffalo School of Dental Medicine faculty and testing agency personnel was launched. The aims of this article are to describe the development and implementation of the resulting Buffalo Model, to highlight ethical advantages in its application, and to identify areas of improvement to be addressed in future iterations. With the Buffalo Model, modifications were made to the traditional exam format in order to integrate the exam into the school curriculum, enabling candidates to take it at various points during their fourth year. In addition, after calibration of school faculty members, 98.5% of cases verified by faculty were accepted by the Commission on Dental Competency Assessments for use in the exam. In two cases, restorative treatment completed during the exam did not meet the school's competency standard. This new approach ameliorates ethical concerns associated with clinical licensure exams because treatment is provided only to patients of record within a sequenced treatment plan and timely and appropriate treatment is provided to all patients. The results of this first year of implementation also suggest that calibrated faculty members will not show bias in the selection of lesions or competency evaluations of candidates. PMID- 27251345 TI - Non-Patient-Based Clinical Licensure Examination for Dentistry in Minnesota: Significance of Decision and Description of Process. AB - In recent years in the United States, there has been heightened interest in offering clinical licensure examination (CLE) alternatives to the live patient based method in dentistry. Fueled by ethical concerns of faculty members at the University of Minnesota School of Dentistry, the state of Minnesota's Board of Dentistry approved a motion in 2009 to provide two CLE options to the school's future predoctoral graduates: a patient-based one, administered by the Central Regional Dental Testing Service, and a non-patient-based one administered by the National Dental Examining Board of Canada (NDEB). The validity of the NDEB written exam and objective structured clinical exam (OSCE) has been verified in a multi-year study. Via five-option, one-best-answer, multiple-choice questions in the written exam and extended match questions with up to 15 answer options in the station-based OSCE, competent candidates are distinguished from those who are incompetent in their didactic knowledge and clinical critical thinking and judgment across all dental disciplines. The action had the additional effects of furthering participation of Minnesota Board of Dentistry members in the University of Minnesota School of Dentistry's competency-based curriculum, of involving the school's faculty in NDEB item development workshops, and, beginning in 2018, of no longer permitting the patient-based CLE option on site. The aim of this article is to describe how this change came about and its effects. PMID- 27251346 TI - Development and Implementation of an Electronic Clinical Formative Assessment: Dental Faculty and Student Perspectives. AB - A traditional summative grading structure, used at Indiana University School of Dentistry (IUSD) for more than 30 years, was identified by faculty as outdated for assessing students' clinical performance. In an effort to change the status quo, a feedback-driven assessment was implemented in 2012 to provide a constructive assessment tool acceptable to both faculty and students. Building on the successful non-graded clinical evaluation employed at Baylor College of Dentistry, IUSD implemented a streamlined electronic formative feedback model (FFM) to assess students' daily clinical performance. An important addition to this evaluation tool was the inclusion of routine student self-assessment opportunities. The aim of this study was to determine faculty and student response to the new assessment instrument. Following training sessions, anonymous satisfaction surveys were examined for the three user groups: clinical faculty (60% response rate), third-year (D3) students (72% response rate), and fourth year (D4) students (57% response rate). In the results, 70% of the responding faculty members preferred the FFM over the summative model; however, 61.8% of the D4 respondents preferred the summative model, reporting insufficient assessment time and low faculty participation. The two groups of students had different responses to the self-assessment component: 70.2% of the D4 respondents appreciated clinical self-assessment compared to 46% of the D3 respondents. Overall, while some components of the FFM assessment were well received, a phased approach to implementation may have facilitated a transition more acceptable to both faculty and students. Improvements are being made in an attempt to increase overall satisfaction. PMID- 27251347 TI - Design and Outcomes of a Comprehensive Care Experience Level System to Evaluate and Monitor Dental Students' Clinical Progress. AB - A Comprehensive Care Experience Level (CCEL) system that is aligned with Commission on Dental Accreditation (CODA) standards, promotes comprehensive care and prevention, and addresses flaws observed in previous Relative Value Units (RVU)-based programs has been implemented at the School of Dental Medicine, Case Western Reserve University since 2011. The purpose of this article is to report on the design, implementation, and preliminary outcomes of this novel clinical evaluation system. With the development of the CCEL concept, it was decided not to award points for procedures performed on competency exams. The reason behind this decision was that exams are not learning opportunities and are evaluated with summative tools. To determine reasonable alternative requirements, production data from previous classes were gathered and translated into CCEL points. These RVU points had been granted selectively only for restorative procedures completed after the initial preparation stage of the treatment plan, and achievement of the required levels was checked at multiple points during the clinical curriculum. Results of the CCEL system showed that low performing students increased their productivity, overall production at graduation increased significantly, and fluoride utilization to prevent caries rose by an order of magnitude over the RVU system. The CCEL program also allowed early identification and remediation of students having difficulty in the clinic. This successful implementation suggests that the CCEL concept has the potential for widespread adoption by dental schools. This method also can be used as a behavior modification tool to achieve specific patient care or clinical educational goals as illustrated by the way caries prevention was promoted through the program. PMID- 27251348 TI - Impact of Community-Based Dental Education on Attainment of ADEA Competencies: Students' Self-Ratings. AB - Fourth-year dental students at the College of Dentistry, University of Nebraska Medical Center participate in a community-based dental education (CBDE) program that includes a four-week rotation in rural dental practices and community health clinics across Nebraska and nearby states. The aim of this study was to assess the impact of participation in the CBDE program on the self-rated competencies of these students. A retrospective survey was administered to students who participated in extramural rotations in two academic years. The survey collected demographic data and asked students to rate themselves on a scale from 1=not competent at all to 5=very competent on attainment of the American Dental Education Association (ADEA) Competencies for the New General Dentist for before and after the rotations. A total of 92 responses were obtained: 43 students for 2011-12 and 49 students for 2012-13 (95% response rate for each cohort). The results showed that the students' mean pre-program self-ratings ranged from 3.28 for the competency domain of Practice Management and Informatics to 3.93 for Professionalism. Their mean post-program self-ratings ranged from 3.76 for Practice Management and Informatics to 4.31 for Professionalism. The students showed a statistically significant increase in self-ratings for all six competency domains. The increase was greatest in the domain of Critical Thinking and least in Communication and Interpersonal Skills. Overall, these results suggest that the CBDE program was effective in improving the students' self perceptions of competence in all six domains and support the idea that a competency-based evaluation of CBDE programs can provide valuable information to dental educators about program effectiveness. PMID- 27251349 TI - Untangling the Web of Influences on Dental Students' Participation in Interprofessional Education Programs. AB - The aim of this study was to explore how dental students involved in an experiential interprofessional education (IPE) program in New Zealand made sense of engaging in this unfamiliar learning environment. Qualitative data gathered from students during group interviews were analyzed to better understand how they assessed the IPE experience. Interviews were audiorecorded and transcribed before analysis of students' comments was undertaken, using constant comparison analysis and taking an inductive approach to the initial coding. Once each of the investigators had gone through his or her own transcripts, they reviewed each other's coding and agreed-upon categories before applying the 3-P model of student learning. Over a three-year period (2012-14), 16 focus groups were conducted with students from multiple health professions. In total, 24 dental students participated. Six categories of comments made in the focus groups were identified: expectations and realizations; not practicing; trade-offs/losses; learning with, from, and about each other; becoming open to a different clinical experience; valuing dental students' participation in IPE; and learning about what dentists do. From these categories, three main themes emerged: becoming a dentist, negotiating IPE experience, and valuing dentistry. The 3-P model highlighted the complexity of IPE, and the challenges suggested that dental students may need extra preparation prior to participating in IPE programs. PMID- 27251350 TI - An Interactive Website to Facilitate In-State Retention of New Dentists and Recruitment to Underserved Areas. AB - Some U.S. states have more difficulty than others in recruiting or retaining dentists. Part of the problem is that often dental students are not aware of opportunities across geographic regions of either their home state or the state where they were educated. With student input, the University of Iowa College of Dentistry and Dental Clinics designed and launched an interactive website that provides basic demographic, economic, and other meaningful information to help dental students locate potential practice locations and identify current employment opportunities in Iowa. Although this website is not a recruitment or retention panacea, it provides an easy method for dental students to explore all or parts of the state as they go about making one of the most important decisions of their careers. The website also provides a showcase for current practitioners and communities to demonstrate what they have to offer as practice opportunities. PMID- 27251351 TI - Honoring Dental Patients' Privacy Rule Right of Access in the Context of Electronic Health Records. AB - A person's right to access his or her protected health information is a core feature of the U.S. Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule. If the information is stored electronically, covered entities must be able to provide patients with some type of machine-readable, electronic copy of their data. The aim of this study was to understand how academic dental institutions execute the Privacy Rule's right of access in the context of electronic health records (EHRs). A validated electronic survey was distributed to the clinical deans of 62 U.S. dental schools during a two-month period in 2014. The response rate to the survey was 53.2% (N=33). However, three surveys were partially completed, and of the 30 completed surveys, the 24 respondents who reported using axiUm as the EHR at their dental school clinic were the ones on which the results were based (38.7% of total schools at the time). Of the responses analyzed, 86% agreed that clinical modules should be considered part of a patient's dental record, and all agreed that student teaching-related modules should not. Great variability existed among these clinical deans as to whether administrative and financial modules should be considered part of a patient record. When patients request their records, close to 50% of responding schools provide the information exclusively on paper. This study found variation among dental schools in their implementation of the Privacy Rule right of access, and although all the respondents had adopted EHRs, a large number return records in paper format. PMID- 27251352 TI - Patient-Centered Communication: Exploring the Dentist's Role in the Era of e Patients and Health 2.0. AB - In today's digital era, people are increasingly relying on the Internet-including social media-to access health information and inform their health decisions. This article describes an exploratory initiative to better understand and define the role of dentists in patient education in the context of e-patients and Health 2.0. This initiative consisted of four phases. In Phase I, an interdisciplinary expert advisory committee was assembled for a roundtable discussion about patients' health information-seeking behaviors online. In Phase II, a pilot case study was conducted, with methods and analysis informed by Phase I recommendations. Phase III consisted of a debriefing conference to outline future areas of research on modernizing health communication strategies. In Phase IV, the findings and working theories were presented to 75 dental students, who then took a survey regarding their perspectives with the objective of guiding potential curriculum design for predoctoral courses. The results of the survey showed that the validity of online content was often secondary to the strength of the network sharing it and that advocacy online could be more effective if it allowed for emotional connections with peers rather than preserving accuracy of the information. Students expressed high interest in learning how to harness modern health communications in their clinical care since the role of the dentist is evolving from giving information to giving personalized guidance against the backdrop of an often contradictory modern information environment. The authors recommend that the dental profession develop patient-centered health communication training for predoctoral students and professional development and continuing education for practicing professionals. PMID- 27251353 TI - Development of a Core Curriculum Framework in Cariology for U.S. Dental Schools. AB - Maintenance of health and preservation of tooth structure through risk-based prevention and patient-centered, evidence-based disease management, reassessed at regular intervals over time, are the cornerstones of present-day caries management. Yet management of caries based on risk assessment that goes beyond restorative care has not had a strong place in curriculum development and competency assessment in U.S. dental schools. The aim of this study was to develop a competency-based core cariology curriculum framework for use in U.S. dental schools. The Section on Cariology of the American Dental Education Association (ADEA) organized a one-day consensus workshop, followed by a meeting program, to adapt the European Core Cariology Curriculum to the needs of U.S. dental education. Participants in the workshop were 73 faculty members from 35 U.S., three Canadian, and four international dental schools. Representatives from all 65 U.S. dental schools were then invited to review and provide feedback on a draft document. A recommended competency statement on caries management was also developed: "Upon graduation, a dentist must be competent in evidence-based detection, diagnosis, risk assessment, prevention, and nonsurgical and surgical management of dental caries, both at the individual and community levels, and be able to reassess the outcomes of interventions over time." This competency statement supports a curriculum framework built around five domains: 1) knowledge base; 2) risk assessment, diagnosis, and synthesis; 3) treatment decision making: preventive strategies and nonsurgical management; 4) treatment decision making: surgical therapy; and 5) evidence-based cariology in clinical and public health practice. Each domain includes objectives and learning outcomes. PMID- 27251354 TI - U.S. Dental School Deans' Views on the Value of Patient-Reported Outcome Measures in Dentistry. AB - There has historically been limited development and utilization of patient reported outcome measures (PROMs) in clinical dentistry. However, in recent years PROMs have been recognized by other health care fields as valuable in the comprehensive assessment of patient outcomes. The aim of this study was to survey deans of U.S. dental schools to better understand their vision for the role of PROMs in the field of dentistry. A 13-question online survey was emailed to the deans of the 64 accredited U.S. dental schools at the time to gather their opinions about the value of patient-reported outcomes in dentistry. The survey consisted of questions in 12 domains such as treatment planning, perceived success/complications of surgery, identification/management of dental pain, psychological and oral function, and insurance payment/reimbursement. Of the 64 deans, 33 responses were received (51.5% response rate), but three surveys were excluded due to incomplete answers, resulting in a final response rate of 46.8%. All respondents reported there was value in utilization of PROMs for understanding a patient's satisfaction of a procedure, a patient's perceived success of dental surgery, identifying dental pain, and managing dental pain. However, there was disagreement among the respondents about utilization of PROMs for the purpose of determining insurance payment and/or reimbursement. Additional steps should be taken to develop clinically appropriate PROMs for dentistry and to determine the appropriate situations in which to use dental PROMs. This study suggests that PROMs should be incorporated into dental school curricula as they will likely play a role in future comprehensive treatment assessment. PMID- 27251355 TI - Second Mesiobuccal Canal Treatment in a Predoctoral Dental Clinic: A Retrospective Clinical Study. AB - The aim of this retrospective clinical study was to evaluate the location and treatment of second canals in mesiobuccal roots (MB2) of first and second maxillary molars in a predoctoral endodontic clinic by the graduating classes of 2008 to 2015. These results were compared to similar clinical studies. Included in the study were 368 root canal treatments performed by 310 third- and fourth year dental students at one U.S. dental school. All cases were done under faculty supervision, and the students were instructed to use dental loupe magnification. Students' evaluation sheets were used to deteremine the total MB2 canals treated in first and second maxillary molars. The results showed that, overall, 72.55% of the teeth had an MB2 canal treated. The frequency was higher in first molars (75.91%) than in second molars (56.92%) (p<0.05). Third-year students were able to detect 39 MB2 canals in 57 maxillary molars (68.42%), while fourth-year students detected 228 MB2 canals in 311 teeth (73.31%) (p>0.05). Under proper supervision by experienced endodontists, these dental students were capable of treating MB2 canals in maxillary molars. The frequency of MB2 canals located and treated by dental students with the assistance of experienced professionals was higher in first than in second molars. No significant difference was found between third- and fourth-year students. The incidence of MB2 canals located and treated in this study was found to be similar to that in other clinical studies. PMID- 27251356 TI - Factors Influencing Dental Educators As They Develop Problem-Based Learning Cases. AB - In problem-based learning (PBL) environments, patient cases encourage students' development of critical thinking and problem-solving. Previous research has found that non-structured patient cases fostered students' critical thinking and problem-solving abilities; however, structured cases dominate in dental PBL. The aim of this study was to explore factors influencing educators as they developed cases for a hybrid PBL dental education program in Canada. In this phenomenological study, semi-structured interviews were used to collect seven educators' experiences with PBL case development. Content analyses with conceptual mapping were triangulated with field notes, researcher memos, and member checking to elucidate codes and themes. There were two major themes and 14 subthemes. The major theme-external factors-involved environmental parameters that influenced educators to develop PBL cases with a definitive problem-solving approach and preferred solution. Structured PBL cases dominated because of limited curricular time for students to explore identified learning issues within a three-session framework. The hybrid PBL dental curriculum further influenced educators to develop structured PBL cases such that content was not duplicated by corresponding lectures. The second major theme-internal factors-encompassed the educators' beliefs and values about teaching and student learning. These educators were enthusiastic about PBL as an instructional strategy, but did not appear to support the PBL philosophy wherein students engage in self-directed, self-exploratory learning. Structured PBL case development occurred when educators believed students needed content expert guidance. Structured PBL cases dominated in the hybrid PBL program because the educators felt students needed guidance in solving the cases to meet the learning objectives within the limited curricular time. PMID- 27251357 TI - World Malaria Day 2016 in the Kingdom of Cambodia: high-level governmental support embodies the WHO call for "political will to end malaria". AB - On World Malaria Day 2016, The Kingdom of Cambodia's National celebrations served as a prime of example of how political will is currently being exercised in Cambodia through high-level governmental support for malaria elimination. The main country event was well-planned and coordinated by the National Programme for Parasitology, Entomology and Malaria Control (CNM), and included key contributions from high-ranking political figures, such as His Excellency (H.E) Mam Bun Heng (Minister of Health), and H.E. Keut Sothea (Governor of Pailin Province). There were more than 1000 attendees, ranging from Village Malaria Workers and high school students to CNM's director and other officials in Pailin Province, Western Cambodia. A strong inter-sectoral participation included attendances from the Ministry of Education and high-level representatives of the Cambodian Armed Forces, as well as Malaria Partners like the World Health Organization. PMID- 27251358 TI - Angiotensin II type 1 receptor antibodies in childhood kidney transplantation. AB - Angiotensin II type 1 receptor antibodies (AT1 RAb) have emerged as non-HLA Ab present in patients with acute AMR and risk of graft loss. Furthermore, AT1 RAb have been shown to increase angiotensin II sensitivity which may play a role in the development of CVD and hypertension. Data on AT1 RAb in stable transplant recipients are lacking. The aim of this study was to analyze the levels of AT1 RAb in a cohort of stable patients after kidney transplantation (tx) in childhood. A cross-sectional study of 30 children (median age 14, range 3-19 yr, median time since tx five yr) and 28 adults who were transplanted in childhood (median age 26, range 20-40 yr, median time since tx 18 yr) transplanted between 1993-2006 and 1983-2002, respectively, was performed. Healthy controls were 51 healthy children (5-8 yr) and 199 healthy donors (median age 56.5 yr, range 42-83 yr). Plasma AT1 RAb were analyzed by immunoassay. Median total AT1 RAb IgG concentration was significantly higher in the pediatric-tx group as compared to the adult-tx group (40.0 and 10.95 U/mL, p < 0.0001). For both groups, the tx group showed higher levels: the pediatric-tx group vs. control group (40.0 vs. 13.3 U/mL, p = 0.0006) and the adult-tx group vs. adult control group (10.95 vs. 6.5 U/mL, p < 0.0001). Age was the strongest indicator of high levels of AT1 RAb IgG (p = 0.0003). AT1 RAb total IgG levels are significantly higher in a stable pediatric-tx cohort as compared to adult-tx patients and healthy controls of comparable age groups. The relevance of our findings in relation to age, time since tx, previous or future rejection, and CVD risk merits future studies. PMID- 27251359 TI - The role of neutralizing antibodies to interferon-beta as a biomarker of persistent MRI activity in multiple sclerosis: a 7-year observational study. AB - PURPOSE: During interferon-beta (IFN-beta) therapy, up to 45 % of patients may develop neutralizing antibodies (NAbs), associated with a decreased efficacy of the drug. We investigated in a real-life setting the impact of NAbs on magnetic resonance imaging (MRI) outcomes in a population of 567 IFN-beta-treated relapsing-remitting (RR) multiple sclerosis (MS) patients up to 7 years. We also evaluated NAbs' role as a biomarker of the persistence of MRI disease activity. METHODS: Patients' sera were tested for NAbs' presence by cytopathic effect (CPE) assay every 6-12 months. MRI scans were performed every 12 months. Generalized hierarchical linear models accounting for within-patient correlation were used to analyze T1 gadolinium-enhancing and new T2 lesions. Moreover, further tests were carried out to assess the overall outcome difference from year 1 to year 7 according to NAb status and the possible interaction between NAb status and time of follow-up. RESULTS: Seventy-five patients (13.2 %) became NAb positive (NAb+) during the follow-up. Considering T1 gadolinium-enhancing (GD+) lesions, we observed a significantly higher incidence in NAb+ patients (52 %, p = 0.0091). Also for new T2 lesions, we found a higher incidence in NAb+ patients (50 %, p = 0.0075). The negative impact of NAbs on the MRI outcomes considered did not change during the follow-up. CONCLUSIONS: Our 7-year results show the negative effect of NAbs on MRI measures of disease activity and confirm their role as a surrogate marker of IFN-beta treatment efficacy. PMID- 27251360 TI - Polypharmacy and medication regimen complexity as factors associated with staff informant rated quality of life in residents of aged care facilities: a cross sectional study. AB - PURPOSE: The purpose of this study is to investigate the association between polypharmacy with health-related quality of life (HRQoL) and medication regimen complexity with HRQoL in residential aged care facilities (RACFs). METHODS: A cross-sectional study of 383 residents from six Australian RACFs was conducted. The primary exposures were polypharmacy (>=9 regular medications) and the validated Medication Regimen Complexity Index (MRCI). The outcome measure was staff informant rated quality of life assessed using the Quality of Life Alzheimer's disease (QoL-AD) scale. Covariates included age, sex, Charlson's comorbidity index, activities of daily living, and dementia severity. Logistic quantile regression was used to characterize the association between polypharmacy and QoL-AD (model 1) and MRCI and QoL-AD (model 2). RESULTS: The median age of the 383 residents was 88 years and 297 (78 %) residents were female. In total, 63 % of residents were exposed to polypharmacy and the median MRCI score (range) was 43.5 (4-113). After adjusting for the covariates, polypharmacy was not associated with either higher or lower QoL-AD scores (estimate -0.02; 95 % confidence interval (CI) -0.165, 0.124; p = 0.78). Similarly, after adjusting for the covariates, MRCI was not associated with either higher or lower QoL-AD scores (estimate -0.0009, 95 % CI -0.005, 0.003; p = 0.63). CONCLUSIONS: These findings suggest that polypharmacy and medication regimen complexity are not associated with staff informant rated HRQoL. Further research is needed to investigate how specific medication classes may impact change in quality of life over time. PMID- 27251361 TI - Pretransplantation Donor-Recipient Pair Seroreactivity Against BK Polyomavirus Predicts Viremia and Nephropathy After Kidney Transplantation. AB - Kidney transplant donors are not currently implicated in predicting BK polyomavirus (BKPyV) infection in kidney transplant recipients. It has been postulated, however, that BKPyV infection originates from the kidney allograft. Because BKPyV seroreactivity correlates with BKPyV replication and thus might mirror the infectious load, we investigated whether BKPyV seroreactivity of the donor predicts viremia and BKPyV-associated nephropathy (BKPyVAN) in the recipient. In a retrospective cohort of 407 living kidney donor-recipient pairs, pretransplantation donor and recipient sera were tested for BKPyV IgG levels and correlated with the occurrence of recipient BKPyV viremia and BKPyVAN within 1 year after transplantation. Donor BKPyV IgG level was strongly associated with BKPyV viremia and BKPyVAN (p < 0.001), whereas recipient BKPyV seroreactivity showed a nonsignificant inverse trend. Pairing of high-BKPyV-seroreactive donors with low-seroreactive recipients resulted in a 10-fold increased risk of BKPyV viremia (hazard ratio 10.1, 95% CI 3.5-29.0, p < 0.001). In multivariate analysis, donor BKPyV seroreactivity was the strongest pretransplantation factor associated with viremia (p < 0.001) and BKPyVAN (p = 0.007). The proportional relationship between donor BKPyV seroreactivity and recipient infection suggests that donor BKPyV seroreactivity reflects the infectious load of the kidney allograft and calls for the use of pretransplantation BKPyV serological testing of (potential) donors and recipients. PMID- 27251362 TI - Urinary Bladder-Relaxant Effect of Kurarinone Depending on Potentiation of Large Conductance Ca2+-Activated K+ Channels. AB - The large-conductance calcium-activated potassium channel (BKCa channel) plays critical roles in smooth muscle relaxation. In urinary bladder smooth muscle, BKCa channel activity underlies the maintenance of the resting membrane potential and repolarization of the spontaneous action potential triggering the phasic contraction. To identify novel BKCa channel activators, we screened a library of natural compounds using a cell-based fluorescence assay and a hyperactive mutant BKCa channel (Lee et al., 2013). From 794 natural compounds, kurarinone, a flavanone from Sophora flavescens, strongly potentiated BKCa channels. When treated from the extracellular side, this compound progressively shifted the conductance-voltage relationship of BKCa channels to more negative voltages and increased the maximum conductance in a dose-dependent manner. Whereas kurarinone strongly potentiated the homomeric BKCa channel composed of only the alpha subunit, its effects were much smaller on heteromeric channels coassembled with auxiliary beta subunits. Although the activation kinetics was not altered significantly, the deactivation of BKCa channels was dramatically slowed by kurarinone treatment. At the single-channel level, kurarinone increased the open probability of the BKCa channel without affecting its single-channel conductance. Kurarinone potently relaxed acetylcholine-induced contraction of rat bladder smooth muscle and thus decreased the micturition frequency of rats with overactive bladder symptoms. These results indicate that kurarinone can directly potentiate BKCa channels and demonstrate the therapeutic potentials of kurarinone and its derivatives for developing antioveractive bladder medications and supplements. PMID- 27251363 TI - Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer. AB - Obesity has emerged as a principal cause of mortality worldwide, reflecting comorbidities including cancer risk, particularly in colorectum. Although this relationship is established epidemiologically, molecular mechanisms linking colorectal cancer and obesity continue to be refined. Guanylyl cyclase C (GUCY2C), a membrane-bound guanylyl cyclase expressed in intestinal epithelial cells, binds the paracrine hormones guanylin and uroguanylin, inducing cGMP signaling in colorectum and small intestine, respectively. Guanylin is the most commonly lost gene product in sporadic colorectal cancer, and its universal loss early in transformation silences GUCY2C, a tumor suppressor, disrupting epithelial homeostasis underlying tumorigenesis. In small intestine, eating induces endocrine secretion of uroguanylin, the afferent limb of a novel gut brain axis that activates hypothalamic GUCY2C-cGMP signaling mediating satiety opposing obesity. Recent studies revealed that diet-induced obesity suppressed guanylin and uroguanylin expression in mice and humans. Hormone loss reflects reversible calorie-induced endoplasmic reticulum stress and the associated unfolded protein response, rather than the endocrine, adipokine, or inflammatory milieu of obesity. Loss of intestinal uroguanylin secretion silences the hypothalamic GUCY2C endocrine axis, creating a feed-forward loop contributing to hyperphagia in obesity. Importantly, calorie-induced guanylin loss silences the GUCY2C-cGMP paracrine axis underlying obesity-induced epithelial dysfunction and colorectal tumorigenesis. Indeed, genetically enforced guanylin replacement eliminated diet-induced intestinal tumorigenesis in mice. Taken together, these observations suggest that GUCY2C hormone axes are at the intersection of obesity and colorectal cancer. Moreover, they suggest that hormone replacement that restores GUCY2C signaling may be a novel therapeutic paradigm to prevent both hyperphagia and intestinal tumorigenesis in obesity. PMID- 27251364 TI - Wild food plants and fungi used in the mycophilous Tibetan community of Zhagana (Tewo County, Gansu, China). AB - BACKGROUND: The aim of the study was to investigate knowledge and use of wild food plants and fungi in a highland valley in the Gannan Tibetan Autonomous Region on the north-eastern edges of the Tibetan Plateau. METHODS: Field research was carried out in four neighbouring villages in a mountain valley of the Diebu (Tewo) county, surrounded by spruce forests. The study consisted of 30 interviews with single informants, or group interviews (altogether 63 informants). Apart from collecting voucher specimens, we also identified fungi using DNA barcoding. RESULTS: We recorded the use of 54 species of vascular plants. We also recorded the use of 22 mushroom taxa, which made up the largest category of wild foods. Fruits formed the largest category of food plants, with 21 species, larger than the wild greens category, which consisted of 20 species eaten after boiling or frying and 7 as raw snacks. We also recorded the alimentary use of 10 species of edible flowers and 3 species with underground edible organs. On average, 20.8 edible taxa were listed per interview (median - 21). The most listed category of wild foods was green vegetables (mean - 7.5 species, median - 8 species), but fruits and mushrooms were listed nearly as frequently (mean - 6.3, median - 6 and mean - 5.8, - median 6 respectively). Other category lists were very short, e.g., flowers (mean - 1.3, median - 1) and underground edible parts (mean - 0.7, median - 1). Wild vegetables are usually boiled and/or fried and served as side-dishes, or their green parts are eaten as snacks during mountain treks (e.g., peeled rhubarb shoots). Wild fruits are mainly collected by children and eaten raw, they are not stored for further use. The most widely used wild staple foods are Potetilla anserina roots, an important ceremonial food served on such occasions as New Year or at funerals. They are boiled and served with sugar and butter. The most important famine plants remembered by people are the aerial bulbils of Persicaria vivipara. Flowers are used as children's snacks - their nectar is sucked. CONCLUSIONS: The number of wild taxa eaten in the studied valley is similar to that of other Tibetan areas. The structure of wild food plant taxa is also very typical for Tibetan speaking areas (e.g., the use of rhubarb shoots, Potentilla anserina, Persicaria vivipara). The studied community show a high level of mycophilia. PMID- 27251365 TI - How do changes in bulk soil organic carbon content affect carbon concentrations in individual soil particle fractions? AB - We test the common assumption that organic carbon (OC) storage occurs on sand sized soil particles only after the OC storage capacity on silt- and clay-sized particles is saturated. Soil samples from a Brookston clay loam in Southwestern Ontario were analysed for the OC concentrations in bulk soil, and on the clay (<2 MUm), silt (2-53 MUm) and sand (53-2000 MUm) particle size fractions. The OC concentrations in bulk soil ranged from 4.7 to 70.8 g C kg(-1) soil. The OC concentrations on all three particle size fractions were significantly related to the OC concentration of bulk soil. However, OC concentration increased slowly toward an apparent maximum on silt and clay, but this maximum was far greater than the maximum predicted by established C sequestration models. In addition, significant increases in OC associated with sand occurred when the bulk soil OC concentration exceeded 30 g C kg(-1), but this increase occurred when the OC concentration on silt + clay was still far below the predicted storage capacity for silt and clay fractions. Since the OC concentrations in all fractions of Brookston clay loam soil continued to increase with increasing C (bulk soil OC content) input, we concluded that the concept of OC storage capacity requires further investigation. PMID- 27251366 TI - Dissolved Divalent Metal and pH Effects on Amino Acid Polymerization: A Thermodynamic Evaluation. AB - Polymerization of amino acids is a fundamentally important step for the chemical evolution of life. Nevertheless, its response to changing environmental conditions has not yet been well understood because of the lack of reliable quantitative information. For thermodynamics, detailed prediction over diverse combinations of temperature and pH has been made only for a few amino acid peptide systems. This study used recently reported thermodynamic dataset for the polymerization of the simplest amino acid "glycine (Gly)" to its short peptides (di-glycine and tri-glycine) to examine chemical and structural characteristics of amino acids and peptides that control the temperature and pH dependence of polymerization. Results showed that the dependency is strongly controlled by the intramolecular distance between the amino and carboxyl groups in an amino acid structure, although the side-chain group role is minor. The polymerization behavior of Gly reported earlier in the literature is therefore expected to be a typical feature for those of alpha-amino acids. Equilibrium calculations were conducted to examine effects of dissolved metals as a function of pH on the monomer-polymer equilibria of Gly. Results showed that metals shift the equilibria toward the monomer side, particularly at neutral and alkaline pH. Metals that form weak interaction with Gly (e.g., Mg2+) have no noticeable influence on the polymerization, although strong interaction engenders significant decrease of the equilibrium concentrations of Gly peptides. Considering chemical and structural characteristics of Gly and Gly peptides that control their interactions with metals, it can be expected that similar responses to the addition of metals are applicable in the polymerization of neutral alpha amino acids. Neutral and alkaline aqueous environments with dissolved metals having high affinity with neutral alpha-amino acids (e.g., Cu2+) are therefore not beneficial places for peptide bond formation on the primitive Earth. PMID- 27251367 TI - Supplementation of procyanidins B2 attenuates photooxidation-induced apoptosis in ARPE-19 cells. AB - During the aging process, dimers of dietary vitamin A accumulated in retinal pigment epithelium (RPE) cells. Vitamin A dimer-mediated photooxidation resulted in RPE apoptosis, which is associated with age-related degenerative disease of retina, leading to blindness. It has been reported that proanthocyanidin-rich grape seed extract reduces oxidative stress in the eye. In this study, we investigated the underlying mechanism of photooxidation-induced apoptosis inhibition by procyanidins B2 (PB2), one of the main components of grape seed proanthocyanidin. To mimic vitamin A dimer-mediated photooxidation, ARPE-19 cells that accumulated vitamin A dimer, A2E, were used as a model system. Exposure of A2E loaded ARPE-19 cells to blue light induced ER stress and resulted in significant apoptosis. Pretreatment of blue light-exposed A2E containing ARPE-19 cells with PB2 inhibited apoptosis, increased the ratio of Bcl-2/Bax in the mitochondria, attenuated ROS and cytochrome c release, and decreased caspase cleavage. Additionally, PB2 inhibited the phosphorylation of ER stress markers elF2alpha and IRE1alpha and reduced CHOP expression. Moreover, PB2 inhibition of apoptosis is dependent on the UPR chaperone GRP78, indicating PB2 inhibits vitamin A dimer-mediated apoptosis in RPE cells by activating the UPR. PMID- 27251368 TI - Neurobiology of early life stress and visceral pain: translational relevance from animal models to patient care. AB - BACKGROUND: Epidemiological studies show that females are twice as likely to receive a diagnosis of irritable bowel syndrome (IBS) than their male counterparts. Despite evidence pointing to a role for sex hormones in the onset or exacerbation of IBS symptoms, the mechanism by which ovarian hormones may predispose women to develop IBS remains largely undefined. On the other hand, there is a growing body of research showing a correlation between reports of early life stress (ELS) and the diagnosis of IBS. Current treatments available for IBS patients target symptom relief including abdominal pain and alterations in bowel habits, but are not directed to the etiology of the disease. PURPOSE: To better understand the mechanisms by which sex hormones and ELS contribute to IBS, animal models have been developed to mirror complex human experiences allowing for longitudinal studies that investigate the lifelong consequences of ELS. These preclinical models have been successful in recapitulating ELS-induced visceral pain. Moreover, in female rats the influence of cycling hormones on visceral hypersensitivity resembles that seen in women with IBS. Such studies suggest that rodent models of ELS may serve as pivotal tools in determining (i) the etiology of IBS, (ii) novel future treatments for IBS, and (iii) improving individualized patient care. The current review aims to shed light on the progress and the challenges observed by clinicians within the field of gastroenterology and the preclinical science aimed at addressing those challenges in an effort to understand and more efficiently treat functional gastrointestinal disorders (FGIDs) in both children and adults. PMID- 27251369 TI - A Z-scheme photocatalyst constructed with an yttrium-tantalum oxynitride and a binuclear Ru(ii) complex for visible-light CO2 reduction. AB - An yttrium-tantalum oxynitride having a band gap of 2.1 eV (absorbing visible light at <580 nm) was applicable as a semiconductor component of a Z-scheme CO2 reduction system operable under visible light, in combination with a binuclear Ru(ii) complex that has strong absorption in the visible region (<600 nm). Excitation of this system with visible light under a CO2 atmosphere induced photocatalytic formation of formic acid with very high selectivity (>99%). PMID- 27251370 TI - The mechanisms of delayed onset type adverse reactions to oseltamivir. AB - Oseltamivir is recommended for the treatment and prophylaxis of influenza in persons at higher risk for influenza complications such as individuals with diabetes, neuropsychiatric illnesses, and respiratory, cardiac, renal, hepatic or haematological diseases. However, a recent Cochrane review reported that reduction of antibody production, renal disorders, hyperglycaemia, psychiatric disorders, and QT prolongation may be related to oseltamivir use. The underlying mechanisms are reviewed. There is decisive evidence that administration of a clinically compatible dose of oseltamivir in mice challenged by a respiratory syncytial virus (RSV) that lacks a neuraminidase gene showed symptom-relieving effects and inhibition of viral clearance. These effects were accompanied by decreased level of T cell surface sialoglycosphingolipid (ganglioside) GM1 that is regulated by the endogenous neuraminidase in response to viral challenge. Clinical and non-clinical evidence supports the view that the usual dose of oseltamivir suppresses pro-inflammatory cytokines such as interferon-gamma, interleukin-6, and tumour necrosis factor-alpha almost completely with partial suppression of viral shedding in human influenza virus infection experiment. Animal toxicity tests support the clinical evidence with regard to renal and cardiac disorders (bradycardia and QT prolongation) and do not disprove the metabolic effect. Reduction of antibody production and cytokine induction and renal, metabolic, cardiac, and prolonged psychiatric disorders after oseltamivir use may be related to inhibition of the host's endogenous neuraminidase. While the usual clinical dose of zanamivir may not have this effect, a higher dose or prolonged administration of zanamivir and other neuraminidase inhibitors may induce similar delayed reactions, including reduction of the antibody and/or cytokine production. PMID- 27251371 TI - Metformin Prevented Dopaminergic Neurotoxicity Induced by 3,4 Methylenedioxymethamphetamine Administration. AB - Metformin, a well-known antidiabetic drug, has recently been proposed to promote neurogenesis and to have a neuroprotective effect on the neurodegenerative processes induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) in models of Parkinson's disease. Interestingly, metformin has antioxidant properties and is involved in regulating the production of cytokines released during the neuroinflammatory process. Several studies have reported that 3,4-methylenedioxymethamphetamine (MDMA), a recreational drug mostly consumed by young adults, produces a persistent loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and caudate putamen (CPu) of mice. The aim of this study was to investigate the potential neuroprotective effect of metformin against short- and long-term neurotoxicity induced by MDMA and its role on MDMA-induced hyperthermia. Adult mice received metformin (2 * 200 mg/kg, 11-h intervals, administered orally), MDMA (4 * 20 mg/kg, 2-h interval, administered intraperitoneally), or MDMA plus metformin (2 * 200 mg/kg, 1 h before the first MDMA administration and 4 h after the last). On the second and third day, mice were treated with vehicle or metformin (1 * 200 mg/kg) and sacrificed 48 h and 7 days after the last MDMA administration. The neuroprotective effect of metformin on MDMA-induced dopaminergic damage was evaluated by dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunohistochemistry in SNc and CPu. Metformin prevented the MDMA-induced loss of TH-positive neurons in the SNc and TH- and DAT-positive fibers in CPu, both at 48 h and 7 days after the last MDMA administration. These results show that metformin is neuroprotective against the short- and long-lasting dopaminergic neurodegeneration induced by MDMA. PMID- 27251372 TI - Effect of vildagliptin and pravastatin combination on cholesterol efflux in adipocytes. AB - Many reports suggested that some statins are almost ineffective in reducing triglycerides or enhancing HDL-C plasma levels, although statin treatment was still efficacious in reducing LDL-C. In diabetic dyslipidemic patients, it may therefore be necessary to use a combination therapy with other drugs to achieve either LDL-C- and triglyceride-lowering or HDL-C-enhancing goals. Such ineffectiveness of statins can be attributed to their effect on the liver X receptor (LXR) which regulates the expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. A decrease in the expression of these transporters eventually leads to decreased cholesterol efflux from peripheral tissues leading to low levels of HDL-C. Although manipulating the LXR pathway may complement the effects of statins, LXR synthetic ligands as T091317 have shown significant hypertriglyceridemic action which limits their use. We recently found that the antidiabetic drug vildagliptin stimulates LXR expression leading to increased ABCB1/ABCG1 expression which improves cholesterol efflux from adipocytes. Therefore, a combination of vildagliptin and statin may provide a solution without the hypertriglyceridemic action observed with LXR agonist. We hypothesize that a combination of vildagliptin and pravastatin will improve cholesterol efflux in adipocytes. Statin-treated 3T3-L1 adipocytes were treated with vildagliptin, and the expression of LXR-ABCA1/ABCG1 cascade and the cholesterol efflux were then determined. Our data indicate that a combination of vildagliptin and pravastatin significantly induces the expression of LXR-ABCA1/ABCG1 cascade and improves cholesterol efflux (P > 0.05) in adipocytes. Our data may explain, at least in part, the improvement in HDL-C levels observed in patients receiving both medications. (c) 2016 IUBMB Life, 68(7):535-543, 2016. PMID- 27251374 TI - Teflon Might Be a Factor Accounting for a Failed Microvascular Decompression in Hemifacial Spasm: A Technical Note. AB - BACKGROUND: Although Teflon is widely adopted for microvascular decompression (MVD) surgery, it has never been addressed for failure analysis. This study analyzed the reasons for failed MVDs with emphasis on the Teflon sponge. METHODS: Among the 685 hemifacial spasm cases between 2010 and 2014, 31 were reoperated on within a week because of unsatisfactory outcome, which was focused on in this study. Intraoperative findings regarding Teflon inserts of these repeat MVDs were reviewed. RESULTS: Among the 38 without satisfactory outcomes, 31 underwent repeat MVDs, and they were all spasm free afterwards. Eventually, the final cure rate was 99.2%. It was found in the repeat MVDs that the failure was attributable to the Teflon insert in most of the cases (74.2%) directly or indirectly. It was caused by improper placement (47.8%), inappropriate size (34.8%) and unsuitable shape (17.4%) of the Teflon sponge. CONCLUSION: Although it is not difficult for an experienced neurosurgeon to discover a neurovascular conflict during the MVD process, the size, shape and location of the Teflon sponge should not be ignored. Basically, the Teflon insert is used to keep the offending artery away from the facial nerve root rather than to isolate it. Therefore, the ideal Teflon sponge should be just small enough to produce a neurovascular separation. PMID- 27251373 TI - A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8(+) T Cells. AB - The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8(+) cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4(+) and CD8(+) T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4(+) and CD8(+) T cells. Furthermore, lymphoid CD8(+) T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8(+) T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8(+) T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine. PMID- 27251375 TI - Immunotherapy-responsive allodynia due to distal acquired demyelinating symmetric (DADS) neuropathy. AB - INTRODUCTION: Distal acquired demyelinating symmetric (DADS) neuropathy is a distal variant of chronic inflammatory demyelinating polyradiculoneuropathy. It is characterized by chronic distal symmetric sensory or sensorimotor deficits. Sensory ataxia is a common clinical presentation. Nerve conduction studies typically show markedly prolonged distal motor latencies. METHODS: We report 2 patients with chronic progressive generalized pain and fatigue, with normal neurological examinations except for allodynia. RESULTS: Nerve conduction studies were typical of DADS neuropathy. Monoclonal protein studies were negative. Cerebrospinal fluid protein levels were elevated. Sural nerve biopsies revealed segmental demyelination and remyelination. One biopsy had marked endoneurial and epineurial lymphocytic infiltration. Immunomodulatory therapy alleviated the pain and fatigue and markedly improved distal motor latencies in both patients. CONCLUSIONS: DADS neuropathy can present with pain and a normal neurological examination apart from allodynia. Nerve conduction studies are necessary for diagnosis. These patients respond to immunotherapy better than typical DADS neuropathy patients with sensory ataxia. Muscle Nerve 54: 973-977, 2016. PMID- 27251376 TI - 3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response. AB - BACKGROUND: The Her2 receptor is overexpressed in up to 25 % of breast cancers and is associated with a poor prognosis. Around half of Her2+ breast cancers also express the estrogen receptor and treatment for such tumours can involve both endocrine and Her2-targeted therapies. However, despite preclinical data supporting the effectiveness of these agents, responses can vary widely in the clinical setting. In light of the increasing evidence pointing to the interplay between the tumour and its extracellular microenvironment as a significant determinant of therapeutic sensitivity and response here we investigated the impact of 3D matrix culture of breast cancer cells on their therapeutic sensitivity. METHODS: A 3D Matrigel-based culture system was established and optimized for the growth of ER+/Her2+ breast cancer cell models. Growth of cells in response to trastuzumab and endocrine agents in 3D culture versus routine monolayer culture were assessed using cell counting and Ki67 staining. Endogenous and trastuzumab-modulated signalling pathway activity in 2D and 3D cultures were assessed using Western blotting. RESULTS: Breast cancer cells in 3D culture displayed an attenuated response to both endocrine agents and trastuzumab compared with cells cultured in traditional 2D monolayers. Underlying this phenomenon was an apparent matrix-induced shift from AKT to MAPK signalling; consequently, suppression of MAPK in 3D cultures restores therapeutic response. CONCLUSION: These data suggest that breast cancer cells in 3D culture display a reduced sensitivity to therapeutic agents which may be mediated by internal MAPK mediated signalling. Targeting of adaptive pathways that maintain growth in 3D culture may represent an effective strategy to improve therapeutic response clinically. PMID- 27251378 TI - Limited significance of curative surgery in Borrmann type IV gastric cancer. AB - Borrmann type IV advanced gastric cancer has a poor prognosis. Although surgical resection remains the only hope for a cure, the role of curative surgery is questionable in this type of cancer. This study defined the role of curative surgery in the prognosis of type IV gastric cancer. We analyzed 168 patients with Borrmann type IV undergoing surgery at Seoul St. Mary's Hospital from 1989 to 2010. We categorized the patients into curative (R0) and non-curative (R1, R2, and non-resection) groups. The curative and non-curative groups comprised 88 and 80 patients, respectively. The preoperative predictive value of Borrmann type IV was 50.5, and 8.9 % of the patients had microscopic resection margin involvement. The 3- to 5-year overall survival (OS) of patients in the curative group was significantly higher than that of in the non-curative group (p < 0.001). However, in a multivariate analysis, curability was not a significant predictor of survival (p = 0.187). In the curative group, the most frequent recurrence site was the peritoneum (85.7 %). Most recurrences occurred within 2 years. The role of surgery for Borrmann type IV is quite limited. Such cases have a poor prognosis even after curative surgery. In addition, microscopic resection margin involvement is frequent in type IV cancer because it is difficult to diagnose preoperatively. Therefore, multimodal diagnostic tools and treatment strategies should be developed for Borrmann type IV gastric cancer. PMID- 27251377 TI - The role of IL-37 in cancer. AB - Interleukin 37 (IL-37) is a new member of the IL-1 family which all have a similar beta-barrel structure. Since its discovery, IL-37 has been studied extensively in immunological field. It has been established that IL-37 possesses anti-inflammatory characteristics both in innate immune response as well as in acquired immune responses by downregulating pro-inflammatory molecules. This review will discuss the role of IL-37 in immunological processes and neoplastic pathogenesis. PMID- 27251379 TI - Anti-Inflammation Effects and Potential Mechanism of Saikosaponins by Regulating Nicotinate and Nicotinamide Metabolism and Arachidonic Acid Metabolism. AB - Inflammation is an important immune response; however, excessive inflammation causes severe tissue damages and secondary inflammatory injuries. The long-term and ongoing uses of routinely used drugs such as non-steroidal anti-inflammatory drugs (NSAIDS) are associated with serious adverse reactions, and not all patients have a well response to them. Consequently, therapeutic products with more safer and less adverse reaction are constantly being sought. Radix Bupleuri, a well-known traditional Chinese medicine (TCM), has been reported to have anti inflammatory effects. However, saikosaponins (SS) as the main pharmacodynamic active ingredient, their pharmacological effects and action mechanism in anti inflammation have not been reported frequently. This study aimed to explore the anti-inflammatory activity of SS and clarify the potential mechanism in acute inflammatory mice induced by subcutaneous injection of formalin in hind paws. Paw edema was detected as an index to evaluate the anti-inflammatory efficacy of SS. Then, a metabolomic method was used to investigate the changed metabolites and potential mechanism of SS. Metabolite profiling was performed by high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). The detection and identification of the changed metabolites were systematically analyzed by multivariate data and pathway analysis. As a result, 12 different potential biomarkers associated with SS in anti-inflammation were identified, including nicotinate, niacinamide, arachidonic acid (AA), and 20 carboxy-leukotriene B4, which are associated with nicotinate and nicotinamide metabolism and arachidonic acid metabolism. The expression levels of biomarkers were effectively modulated towards the normal range by SS. It indicated that SS show their effective anti-inflammatory effects through regulating nicotinate and nicotinamide metabolism and arachidonic acid metabolism. PMID- 27251380 TI - The Effects of Rifampin, Povidone-Iodine and Hydrogen Peroxide on the Formation of Epidural Fibrosis in the Experimental Epidural Fibrosis Model. AB - The aim of the study was to determine the effect of direct application of rifampin, povidone-iodine, and hydrogen peroxide on the formation of epidural fibrosis in rats. Forty-eight adult male Wistar albino rats were equally and randomly divided into four groups (laminectomy, topical rifampin, topical povidone-iodine, and topical hydrogen peroxide). Laminectomy was performed at the T12 level in all rats. Four weeks later, the extent of epidural fibrosis was assessed both macroscopically and histopathologically. ANOVA test was used for the evaluation of dural thickness. Kruskal-Wallis test was used for the pathology and macroscopic evaluation. Chi-square test was used for evaluation of the arachnoid involvement. p value <0.05 was accepted as statistically significant. Our data revealed that topical application of both povidone-iodine and hydrogen peroxide were effective in reducing epidural fibrosis formation. The results of our study provide the experimental evidence of the preventive effects of topical application of povidone-iodine and hydrogen peroxide over epidural fibrosis. PMID- 27251382 TI - The Vulnerable Newborn Brain: Imaging Patterns of Acquired Perinatal Injury. AB - BACKGROUND: Over the past two decades, imaging techniques have allowed for better visualization of the newborn brain. This has enabled us to detect patterns, understand mechanisms and guide diagnosis and treatment. OBJECTIVES: The purpose of this review is to discuss imaging characteristics of acquired perinatal brain injury. METHODS: Through literature review and the author's research, this review assesses published data on the distinct imaging patterns that occur in the neonatal period due to acquired brain insults. RESULTS: In the term brain, susceptibility to hypoxia-ischemia, hypoglycemia and hyperbilirubinemia results in unique patterns of injury. Stroke commonly occurs in the newborn period. Infections, especially viral, have distinct patterns of white matter injury. In the preterm brain, white matter injury occurs commonly and is affected by postnatal growth, stress and infection. The cerebellum is uniquely vulnerable during this period, with resultant hemorrhages in almost half of preterm infants. Cerebellar growth is affected by intraventricular hemorrhage, drugs and placental pathology. Periventricular hemorrhagic infarction is the most serious consequence of the spectrum of intraventricular hemorrhage and results in profound disabilities. CONCLUSIONS: Taken together, the acquired perinatal brain injuries can have lifelong devastating consequences, so the search for therapies must continue. PMID- 27251381 TI - Psychology, replication & beyond. AB - Modern psychology is apparently in crisis and the prevailing view is that this partly reflects an inability to replicate past findings. If a crisis does exists, then it is some kind of 'chronic' crisis, as psychologists have been censuring themselves over replicability for decades. While the debate in psychology is not new, the lack of progress across the decades is disappointing. Recently though, we have seen a veritable surfeit of debate alongside multiple orchestrated and well-publicised replication initiatives. The spotlight is being shone on certain areas and although not everyone agrees on how we should interpret the outcomes, the debate is happening and impassioned. The issue of reproducibility occupies a central place in our whig history of psychology. PMID- 27251383 TI - Debate on whether Tamiflu prevents flu deaths reignites after new analysis. PMID- 27251384 TI - The Impact of an Online Crowdsourcing Diagnostic Tool on Health Care Utilization: A Case Study Using a Novel Approach to Retrospective Claims Analysis. AB - BACKGROUND: Patients with difficult medical cases often remain undiagnosed despite visiting multiple physicians. A new online platform, CrowdMed, uses crowdsourcing to quickly and efficiently reach an accurate diagnosis for these patients. OBJECTIVE: This study sought to evaluate whether CrowdMed decreased health care utilization for patients who have used the service. METHODS: Novel, electronic methods of patient recruitment and data collection were utilized. Patients who completed cases on CrowdMed's platform between July 2014 and April 2015 were recruited for the study via email and screened via an online survey. After providing eConsent, participants provided identifying information used to access their medical claims data, which was retrieved through a third-party web application program interface (API). Utilization metrics including frequency of provider visits and medical charges were compared pre- and post-case resolution to assess the impact of resolving a case on CrowdMed. RESULTS: Of 45 CrowdMed users who completed the study survey, comprehensive claims data was available via API for 13 participants, who made up the final enrolled sample. There were a total of 221 health care provider visits collected for the study participants, with service dates ranging from September 2013 to July 2015. Frequency of provider visits was significantly lower after resolution of a case on CrowdMed (mean of 1.07 visits per month pre-resolution vs. 0.65 visits per month post resolution, P=.01). Medical charges were also significantly lower after case resolution (mean of US $719.70 per month pre-resolution vs. US $516.79 per month post-resolution, P=.03). There was no significant relationship between study results and disease onset date, and there was no evidence of regression to the mean influencing results. CONCLUSIONS: This study employed technology-enabled methods to demonstrate that patients who used CrowdMed had lower health care utilization after case resolution. However, since the final sample size was limited, results should be interpreted as a case study. Despite this limitation, the statistically significant results suggest that online crowdsourcing shows promise as an efficient method of solving difficult medical cases. PMID- 27251385 TI - Thermo-therapeutic applications of chitosan- and PEG-coated NiFe2O4 nanoparticles. AB - The paper reports the thermo-therapeutic applications of chitosan- and PEG-coated nickel ferrite (NiFe2O4) nanoparticles. In this study NiFe2O4 nanoparticles were synthesized by the co-precipitation method, tuning the particle size through heat treatment in the temperature range from 200-800 degrees C for 3 h. XRD and TEM analysis revealed that the the ultrafine nanoparticles were of size 2-58 nm. Crystallinity of the NiFe2O4 nanoparticles in the as-dried condition with the particle size ~2-3 nm was confirmed from the presence of a lattice fringe in the HRTEM image. VSM measurements showed that a superparamagnetic/ferromagnetic transition occurs with increasing particle size, which was further confirmed by Mossbauer spectroscopy. The nickel ferrite nanoparticles with optimum particle size of 10 nm were then coated with materials commonly used for biomedical applications, i.e. chitosan and PEG, to form homogeneous suspensions. The hydrodynamic diameter and the polydispersity index (PDI) were analyzed by dynamic light scattering at the physiological temperature of 37 degrees C and found to be 187 nm and 0.21 for chitosan-coated nanoparticles and 285 nm and 0.32 for PEG coated ones. The specific loss power of rf induction heating by the set-up for hyperthermia and r 2 relaxivity by the nuclear magnetic resonance were determined. The results of induction heating measurements showed that the temperature attained by the nanoparticles of size 10 nm and concentration of about 20 mg ml(-1) was >70 degrees C (for chitosan) and >64 degrees C (for PEG). It has been demonstrated that the required temperature for hyperthermia heating could be tuned by tuning the particle size, shape and magnetization and the concentration of solution. For other potential biomedical applications of the NiFe2O4 nanoparticle solution, e.g. magnetic resonance imaging, the NMR studies yielded the T 1 and T 2 relaxivities as 0.348 and 89 mM(-1) s(-1) respectively. The fact that the T 2 relaxivity is orders of magnitude higher than T 1 indicates that this is suitable as a T 2 contrast agent for magnetic resonance imaging. PMID- 27251386 TI - Language Matters. PMID- 27251387 TI - In Tribute: Charles Magistro-The Shoemaker's Son. PMID- 27251388 TI - Chuang L, Wu C, Lin K, Hsieh C. Relative and Absolute Reliability of a Vertical Numerical Pain Rating Scale Supplemented With a Faces Pain Scale After Stroke. Phys Ther. 2014;94:129-138. PMID- 27251389 TI - Research investment implications of shifts in the global geography of wheat stripe rust. AB - Breeding new crop varieties with resistance to the biotic stresses that undermine crop yields is tantamount to increasing the amount and quality of biological capital in agriculture. However, the success of genes that confer resistance to pests induces a co-evolutionary response that depreciates the biological capital embodied in the crop, as pests evolve the capacity to overcome the crop's new defences. Thus, simply maintaining this biological capital, and the beneficial production and economic outcomes it bestows, requires continual reinvestment in new crop defences. Here we use observed and modelled data on stripe rust occurrence to gauge changes in the geographic spread of the disease over recent decades. We document a significant increase in the spread of stripe rust since 1960, with 88% of the world's wheat production now susceptible to infection. Using a probabilistic Monte Carlo simulation model we estimate that 5.47 million tonnes of wheat are lost to the pathogen each year, equivalent to a loss of US$979 million per year. Comparing the cost of developing stripe-rust-resistant varieties of wheat with the cost of stripe-rust-induced yield losses, we estimate that a sustained annual research investment of at least US$32 million into stripe rust resistance is economically justified. PMID- 27251390 TI - Intensity of a pulse of RSL4 transcription factor synthesis determines Arabidopsis root hair cell size. AB - Cell size is determined by the duration and rate of growth and plays a central role in cell function. Root hairs are tip-growing cellular projections that emerge from the root epidermis and explore the soil to acquire nutrients and water(1). Previously we demonstrated that the basic helix-loop-helix transcription factor root hair defective 6-like 4 (RSL4) is necessary and sufficient for root hair growth(2). Here we show that RSL4 is synthesized in a 4 h pulse at the initiation of hair elongation and is gradually degraded by the 26S proteasome. The amount of RSL4 synthesis during this pulse is modulated as part of a root hair growth response to low phosphate. RSL4 synthesis increases in low phosphate and this increase prolongs the growth phase, resulting in the development of long root hairs. Our data demonstrate that the amount of RSL4 synthesized during the pulse directly determines the final size of the differentiated root hair cell. We propose that the modulation of growth-promoting transcription factors by external cues could be a general mechanism for the regulation of cell growth by environmental factors during development. PMID- 27251391 TI - Larger trees suffer most during drought in forests worldwide. AB - The frequency of severe droughts is increasing in many regions around the world as a result of climate change(1-3). Droughts alter the structure and function of forests(4,5). Site- and region-specific studies suggest that large trees, which play keystone roles in forests(6) and can be disproportionately important to ecosystem carbon storage(7) and hydrology(8), exhibit greater sensitivity to drought than small trees(4,5,9,10). Here, we synthesize data on tree growth and mortality collected during 40 drought events in forests worldwide to see whether this size-dependent sensitivity to drought holds more widely. We find that droughts consistently had a more detrimental impact on the growth and mortality rates of larger trees. Moreover, drought-related mortality increased with tree size in 65% of the droughts examined, especially when community-wide mortality was high or when bark beetles were present. The more pronounced drought sensitivity of larger trees could be underpinned by greater inherent vulnerability to hydraulic stress(11-14), the higher radiation and evaporative demand experienced by exposed crowns(4,15), and the tendency for bark beetles to preferentially attack larger trees(16). We suggest that future droughts will have a more detrimental impact on the growth and mortality of larger trees, potentially exacerbating feedbacks to climate change. PMID- 27251392 TI - An RLP23-SOBIR1-BAK1 complex mediates NLP-triggered immunity. AB - Plants and animals employ innate immune systems to cope with microbial infection. Pattern-triggered immunity relies on the recognition of microbe-derived patterns by pattern recognition receptors (PRRs). Necrosis and ethylene-inducing peptide 1 like proteins (NLPs) constitute plant immunogenic patterns that are unique, as these proteins are produced by multiple prokaryotic (bacterial) and eukaryotic (fungal, oomycete) species. Here we show that the leucine-rich repeat receptor protein (LRR-RP) RLP23 binds in vivo to a conserved 20-amino-acid fragment found in most NLPs (nlp20), thereby mediating immune activation in Arabidopsis thaliana. RLP23 forms a constitutive, ligand-independent complex with the LRR receptor kinase (LRR-RK) SOBIR1 (Suppressor of Brassinosteroid insensitive 1 (BRI1)-associated kinase (BAK1)-interacting receptor kinase 1), and recruits a second LRR-RK, BAK1, into a tripartite complex upon ligand binding. Stable, ectopic expression of RLP23 in potato (Solanum tuberosum) confers nlp20 pattern recognition and enhanced immunity to destructive oomycete and fungal plant pathogens, such as Phytophthora infestans and Sclerotinia sclerotiorum. PRRs that recognize widespread microbial patterns might be particularly suited for engineering immunity in crop plants. PMID- 27251393 TI - Faecal mimicry by seeds ensures dispersal by dung beetles. AB - The large brown, round, strongly scented seeds of Ceratocaryum argenteum (Restionaceae) emit many volatiles found to be present in herbivore dung. These seeds attract dung beetles that roll and bury them. As the seeds are hard and offer no reward to the dung beetles, this is a remarkable example of deception in plant seed dispersal. PMID- 27251395 TI - Establishing a CRISPR-Cas-like immune system conferring DNA virus resistance in plants. AB - CRISPR-Cas (clustered, regularly interspaced short palindromic repeats-CRISPR associated proteins) is an adaptive immune system in many archaea and bacteria that cleaves foreign DNA on the basis of sequence complementarity. Here, using the geminivirus, beet severe curly top virus (BSCTV), transient assays performed in Nicotiana benthamiana demonstrate that the sgRNA-Cas9 constructs inhibit virus accumulation and introduce mutations at the target sequences. Further, transgenic Arabidopsis and N. benthamiana plants overexpressing sgRNA-Cas9 are highly resistant to virus infection. PMID- 27251396 TI - Stingless bees (Melipona subnitida) adjust brood production rather than foraging activity in response to changes in pollen stores. AB - Highly eusocial bees (honey bees and stingless bees) sustain their colonies through periods of resource scarcity by food stored within the nest. The protein supply necessary for successful brood production is ensured through adjustments of the colonies' pollen foraging according to the availability of this resource in the environment. In honey bees Apis mellifera, in addition, pollen foraging is regulated through the broods' demand for this resource. Here, we investigated the influence of the colony's pollen store level on pollen foraging and brood production in stingless bees (Melipona subnitida). When pollen was added to the nests, colonies increased their brood production and reduced their pollen foraging within 24 h. On the other hand, when pollen reserves were removed, colonies significantly reduced their brood production. In strong contrast to A. mellifera; however, M. subnitida did not significantly increase its pollen foraging activity under poor pollen store conditions. This difference concerning the regulation of pollen foraging may be due to differences regarding the mechanism of brood provisioning. Honey bees progressively feed young larvae and, consequently, require a constant pollen supply. Stingless bees, by contrast, mass provision their brood cells and temporary absence of pollen storage will not immediately result in substantial brood loss. PMID- 27251397 TI - Risk factors of postthrombotic syndrome before and after deep venous thrombosis treatment. AB - Postthrombotic syndrome is the most common complication after deep venous thrombosis. Postthrombotic syndrome is a debilitating disease and associated with decreased quality of life and high healthcare costs. Postthrombotic syndrome is a chronic disease, and causative treatment options are limited. Prevention of postthrombotic syndrome is therefore very important. Not all patients develop postthrombotic syndrome. Risk factors have been identified to try to predict the risk of developing postthrombotic syndrome. Age, gender, and recurrent deep venous thrombosis are factors that cannot be changed. Deep venous thrombosis location and extent seem to predict severity of postthrombotic syndrome and are potentially suitable as patient selection criteria. Residual thrombosis and reflux are known to increase the incidence of postthrombotic syndrome, but are of limited use. More recently developed treatment options for deep venous thrombosis, such as new oral factor X inhibitors and catheter-directed thrombolysis, are available at the moment. Catheter-directed thrombolysis shows promising results in reducing the incidence of postthrombotic syndrome after deep venous thrombosis. The role of new oral factor X inhibitors in preventing postthrombotic syndrome is still to be determined. PMID- 27251394 TI - High proportion of cactus species threatened with extinction. AB - A high proportion of plant species is predicted to be threatened with extinction in the near future. However, the threat status of only a small number has been evaluated compared with key animal groups, rendering the magnitude and nature of the risks plants face unclear. Here we report the results of a global species assessment for the largest plant taxon evaluated to date under the International Union for Conservation of Nature (IUCN) Red List Categories and Criteria, the iconic Cactaceae (cacti). We show that cacti are among the most threatened taxonomic groups assessed to date, with 31% of the 1,478 evaluated species threatened, demonstrating the high anthropogenic pressures on biodiversity in arid lands. The distribution of threatened species and the predominant threatening processes and drivers are different to those described for other taxa. The most significant threat processes comprise land conversion to agriculture and aquaculture, collection as biological resources, and residential and commercial development. The dominant drivers of extinction risk are the unscrupulous collection of live plants and seeds for horticultural trade and private ornamental collections, smallholder livestock ranching and smallholder annual agriculture. Our findings demonstrate that global species assessments are readily achievable for major groups of plants with relatively moderate resources, and highlight different conservation priorities and actions to those derived from species assessments of key animal groups. PMID- 27251398 TI - Exploring approaches to patient safety: the case of spinal manipulation therapy. AB - BACKGROUND: The purpose of this study was to gain insight into the current safety culture around the use of spinal manipulation therapy (SMT) by regulated health professionals in Canada and to explore perceptions of readiness for implementing formal mechanisms for tracking associated adverse events. METHODS: Fifty-six semi structured telephone interviews were conducted with professional leaders and frontline practitioners in chiropractic, physiotherapy, naturopathy and medicine, all professions regulated to perform SMT in the provinces of Alberta and Ontario Canada. Interviews were digitally audio-recorded for verbatim transcription. Transcripts were entered into HyperResearch software for qualitative data analysis and were coded for both anticipated and emergent themes using the constant comparative method. A thematic, descriptive analysis was produced. RESULTS: The safety culture around SMT is characterized by substantial disagreement about its actual rather than putative risks. Competing intra- and inter-professional narratives further cloud the safety picture. Participants felt that safety talk is sometimes conflated with competition for business in the context of fee-for-service healthcare delivery by several professions with overlapping scopes of practice. Both professional leaders and frontline practitioners perceived multiple barriers to the implementation of an incident reporting system for SMT. CONCLUSIONS: The established 'measure and manage' approach to patient safety is difficult to apply to care which is geographically dispersed and delivered by practitioners in multiple professions with overlapping scopes of practice, primarily in a fee-for-service model. Collaboration across professions on models that allow practitioners to share information anonymously and help practitioners learn from the reported incidents is needed. PMID- 27251400 TI - Computer-aided rational design of novel EBF analogues with an aromatic ring. AB - Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-beta-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized pi-pi and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1-D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. Graphical abstract The design strategy of new EBF analogues based on the OBP7 structure. PMID- 27251399 TI - The Influence of Age on the Diagnostic Performance of White Blood Cell Count and Absolute Neutrophil Count in Suspected Pediatric Appendicitis. AB - OBJECTIVE: White blood cell (WBC) count and absolute neutrophil count (ANC) are a standard part of the evaluation of suspected appendicitis. Specific threshold values are utilized in clinical pathways, but the discriminatory value of WBC count and ANC may vary by age. The objective of this study was to investigate whether the diagnostic value of WBC count and ANC varies across age groups and whether diagnostic thresholds should be age-adjusted. METHODS: This is a multicenter prospective observational study of patients aged 3-18 years who were evaluated for appendicitis. Receiver operator characteristic curves were developed to assess overall discriminative power of WBC count and ANC across three age groups: <5, 5-11, and 12-18 years of age. Diagnostic performance of WBC count and ANC was then assessed at specific cut-points. RESULTS: A total of 2,133 patients with a median age of 10.9 years (interquartile range = 8.0-13.9 years) were studied. Forty-one percent had appendicitis. The area under the curve (AUC) for WBC count was 0.69 (95% confidence interval [CI] = 0.61 to 0.77) for patients < 5 years of age, 0.76 (95% CI = 0.73 to 0.79) for 5-11 years of age, and 0.83 (95% CI = 0.81 to 0.86) for 12-18 years of age. The AUCs for ANC across age groups mirrored WBC performance. At a commonly utilized WBC cut-point of 10,000/mm3 , the sensitivity decreased with increasing age: 95% (<5 years), 91% (5-11 years), and 89% (12-18 years) whereas specificity increased by age: 36% (<5 years), 49% (5-12 years), and 64% (12-18 years). CONCLUSION: WBC count and ANC had better diagnostic performance with increasing age. Age-adjusted values of WBC count or ANC should be considered in diagnostic strategies for suspected pediatric appendicitis. PMID- 27251401 TI - High breast milk IL-1beta level is associated with reduced risk of childhood eczema. AB - BACKGROUND: We recently demonstrated a dual effect of breastfeeding with increased risk of eczema and decreased risk of wheezing in early childhood by increasing breastfeeding length. We hypothesize that immune mediators in breast milk could explain such association either through a direct effect or as a surrogate marker of maternal immune constitution. OBJECTIVE: To investigate the possible association between cytokine and chemokine levels in breast milk and development of eczema and recurrent wheeze during early childhood. METHODS: Levels of 19 pro-inflammatory and immunoregulatory cytokines and chemokines were measured in 223 breast milk samples from mothers in the Copenhagen Prospective Study on Asthma in Childhood2000 (COPSAC) high-risk birth cohort. Eczema and recurrent wheeze at the age of 0-3 years were prospectively diagnosed by COPSAC physicians adherent to predefined validated algorithms. Association analyses were performed by Cox regression adjusting for potential confounding factors and by multivariable principal component analysis. RESULTS: Increased IL-1beta in breast milk (>= 0.7 pg/mL) was associated with more than a halved risk of eczema before age three (aHR = 0.41; 95% CI = 0.24-0.68; P < 0.001), which remained significant after false discovery rate adjustment (P = 0.008). The principal component analysis confirmed that a mediator pattern dominated by high levels of IL-1beta, IL-17A, and CCL17 and low levels of CXCL1 and TSLP in breast milk protected against eczema (aHR = 0.82; 95% CI = 0.68-0.98; P = 0.03). No associations were observed for recurrent wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Elevated breast milk IL-1beta level was associated with decreased risk of early childhood eczema suggesting either a direct protective effect of IL-1beta or IL-1b acting as a proxy for a healthy maternal immune system protecting high-risk offspring from eczema. PMID- 27251402 TI - Socio-Genomics and Structural Competency. AB - Adverse developmental exposures and pathologies of the social environment make vastly greater contributions to the leading health burdens in society than currently known genotypic information. Yet, while patients now commonly bring information on single alleles to the attention of their healthcare team, the former conditions are only rarely considered with respect to future health outcomes. This manuscript aims to integrate social environmental influences in genetic predictive models of disease risk. Healthcare providers must be educated to better understand genetic risks for complex diseases and the specific health consequences of societal adversities, to facilitate patient education, disease prevention, and the optimal care in order to achieve positive health outcomes for those with early trauma or other social disadvantage. PMID- 27251403 TI - Genomic Testing in The Paediatric Population: Ethical Considerations in Light of Recent Policy Statements. AB - Genomic testing is rapidly becoming established in clinical practice and research. In this paper we consider the ethical issues arising in genomic testing in children, focusing on the clinical context. After describing how genomics can be said to depart from genetics in ethically relevant ways, we introduce two case studies involving ethical issues in paediatric genomic testing. We then summarise and critically engage with recent professional statements regarding genomic testing in children; notably the 2015 position statement from the American Society for Human Genetics. To provide a conceptual framework for these debates, we then synthesise recent bioethics literature regarding appropriate concepts to use when making decisions regarding children, and applying them to genomic testing. We recommend an approach to genomic testing in children that is child focused and flexibly applied, driven by a core clinical question. Finally, we examine the role that age and emerging capacity should play in these debates. PMID- 27251404 TI - Semiconductor Whole Exome Sequencing for the Identification of Genetic Variants in Colombian Patients Clinically Diagnosed with Long QT Syndrome. AB - BACKGROUND AND OBJECTIVE: Inherited long QT syndrome (LQTS) is a cardiac channelopathy characterized by a prolongation of QT interval and the risk of syncope, cardiac arrest, and sudden cardiac death. Genetic diagnosis of LQTS is critical in medical practice as results can guide adequate management of patients and distinguish phenocopies such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, extensive screening of large genomic regions is required in order to reliably identify genetic causes. Semiconductor whole exome sequencing (WES) is a promising approach for the identification of variants in the coding regions of most human genes. METHODS: DNA samples from 21 Colombian patients clinically diagnosed with LQTS were enriched for coding regions using multiplex polymerase chain reaction (PCR) and subjected to WES using a semiconductor sequencer. RESULTS: Semiconductor WES showed mean coverage of 93.6 % for all coding regions relevant to LQTS at >10* depth with high intra- and inter-assay depth heterogeneity. Fifteen variants were detected in 12 patients in genes associated with LQTS. Three variants were identified in three patients in genes associated with CPVT. Co-segregation analysis was performed when possible. All variants were analyzed with two pathogenicity prediction algorithms. The overall prevalence of LQTS and CPVT variants in our cohort was 71.4 %. All LQTS variants previously identified through commercial genetic testing were identified. CONCLUSION: Standardized WES assays can be easily implemented, often at a lower cost than sequencing panels. Our results show that WES can identify LQTS-causing mutations and permits differential diagnosis of related conditions in a real-world clinical setting. However, high heterogeneity in sequencing depth and low coverage in the most relevant genes is expected to be associated with reduced analytical sensitivity. PMID- 27251405 TI - The impact of changing economic conditions on overweight risk among children in California from 2008 to 2012. AB - BACKGROUND: The recent economic recession represents an opportunity to test whether decreases in economic resources may have deleterious consequences on childhood overweight/obesity risk. METHODS: We investigated the association between indicators of changing macroeconomic conditions from 2008 to 2012 and overweight/obesity risk among school-aged children in California (n=1 741 712) using longitudinal anthropometric measurements. Multivariate regression, with individual and county fixed effects, was used to examine the effects of annual county-level unemployment and foreclosure rates on risk of child overweight/obesity, overall and among subgroups (race/ethnicity, sex, county level median household income and county-level urban/rural status). RESULTS: From 2008 to 2012, ~38% of children were overweight/obese and unemployment and foreclosure rates averaged 11% and 6.9%, respectively. A 1-percentage point (pp) increase in unemployment was associated with a 1.4 pp (95% CI 1.3 to 1.5) increase in overweight/obesity risk. Therefore, a child of average weight could expect a 14% increase in their body mass index z-score in association with a 1 pp increase in unemployment during the study period. We found some differences in the magnitude of the effects for unemployment among demographic subgroups, with the largest effects observed for unemployment among American Indians and Pacific Islanders. CONCLUSIONS: Comparing children to themselves over time, we provide evidence that increases in county-level unemployment are associated with increased overweight/obesity risk. Given that overweight among children with lower economic resources remains a challenge for public health, these findings highlight the importance of policy-level approaches, which aim to mitigate the impact of decreased resources as economic conditions change. PMID- 27251406 TI - Exercise duration-matched interval and continuous sprint cycling induce similar increases in AMPK phosphorylation, PGC-1alpha and VEGF mRNA expression in trained individuals. AB - PURPOSE: The effects of low-volume interval and continuous 'all-out' cycling, matched for total exercise duration, on mitochondrial and angiogenic cell signalling was investigated in trained individuals. METHODS: In a repeated measures design, 8 trained males ([Formula: see text], 57 +/- 7 ml kg(-1) min( 1)) performed two cycling exercise protocols; interval (INT, 4 * 30 s maximal sprints interspersed by 4 min passive recovery) or continuous (CON, 2 min continuous maximal sprint). Muscle biopsies were obtained before, immediately after and 3 h post-exercise. RESULTS: Total work was 53 % greater (P = 0.01) in INT compared to CON (71.2 +/- 7.3 vs. 46.3 +/- 2.7 kJ, respectively). Phosphorylation of AMPK(Thr172) increased by a similar magnitude (P = 0.347) immediately post INT and CON (1.6 +/- 0.2 and 1.3 +/- 0.3 fold, respectively; P = 0.011), before returning to resting values at 3 h post-exercise. mRNA expression of PGC-1alpha (7.1 +/- 2.1 vs. 5.5 +/- 1.8 fold; P = 0.007), VEGF (3.5 +/- 1.2 vs. 4.3 +/- 1.8 fold; P = 0.02) and HIF-1alpha (2.0 +/- 0.5 vs. 1.5 +/- 0.3 fold; P = 0.04) increased at 3 h post-exercise in response to INT and CON, respectively; the magnitude of which were not different between protocols. CONCLUSIONS: Despite differences in total work done, low-volume INT and CON 'all out' cycling, matched for exercise duration, provides a similar stimulus for the induction of mitochondrial and angiogenic cell signalling pathways in trained skeletal muscle. PMID- 27251407 TI - The effect of vigorous running and cycling on serum COMP, lubricin, and femoral cartilage thickness: a pilot study. AB - PURPOSE: Our aim was to investigate lubricin, cartilage oligomeric matrix protein (COMP), and femoral cartilage deformation in response to different biomechanical loading of the knee joint (running vs cycling). METHODS: Serum lubricin and COMP concentrations (enzyme-linked immunosorbent assay), and femoral cartilage thickness (suprapatellar transverse ultrasonography) were determined in 11 male runners (age: 40 +/- 6 years; weight: 76 +/- 8 kg) and 11 male cyclists (35 +/- 12 years; 75 +/- 5 kg) at baseline, immediately after, and 30 min after vigorous exercise (time trial: 10-km run or 25-km cycle). RESULTS: At baseline, lubricin (runners: 104.0 +/- 19.8 ng/ml; cyclists: 119.1 +/- 23.9 ng/ml) and COMP (runners: 804.1 +/- 87.5 ng/ml; cyclists: 693.0 +/- 84.7 ng/ml) did not significantly differ; however, vigorous exercise was accompanied by an increase in lubricin (cyclists: 39.4 %; p < 0.05; runners: 56.9 %; p < 0.05) and COMP (cyclists: 32.1 %; p < 0.05; runners: 14.2 %; p = 0.14) that returned toward baseline following 30 min of rest (p < 0.05). No between-group differences were observed for baseline cartilage thickness at the intercondyle notch, medial condyle, and lateral condyle, and vigorous exercise did not result in significant change for either group. CONCLUSIONS: In the absence of ultrasonographic knee cartilage deformation, the response of serum lubricin and COMP following acute vigorous exercise indicates an increase in joint lubrication and cartilage metabolism, respectively, which appears largely independent of exercise modality. PMID- 27251408 TI - Reversible hard palate hyperplasia associated with amlodipine use: case report. AB - Calcium channel blockers (CCBs) are medications often used in the clinical management of hypertension and coronary artery disease. Gingival enlargement is a common side effect of CCB administration with no other oral tissue hyperplasia being reported. Thus, gingival enlargement is considered to be a tissue-specific side effect of CCBs. Here, we report for the first time a case of CCB-related palate hyperplasia in a patient suffering from oral lichen planus and the possible reasons for its occurrence. PMID- 27251409 TI - miRNA-124 modulates lung carcinoma cell migration and invasion. AB - OBJECTIVES: Lung cancer remains the leading cause of cancer-related mortality worldwide. Recently, accumulating studies have evidenced that microRNAs (miRNAs) contribute to the carcinogenesis of lung cancer through acting as either oncogenes or tumor suppressors. The purpose of our study was to investigate the functional role of miR-124 in lung cancer. METHODS: The expression of miR-124 was assessed by real-time RT-PCR in non-small cell lung cancer (NSCLC) tissues in comparison to its adjacent normal tissues. After transfection with miR-124 Mimics or negative controls into A549 cells, migration and invasion assays, apoptosis, and cell viability were evaluated. Luciferase reporter assay and RT-PCR were performed to explore whether zinc finger e-box binding homeobox 1 (ZEB1) was a target of miR-124. Further, the effects of miR-124 Mimic on migration and invasion were assessed after overexpression of ZEB1. RESULTS: MiR-124 expression was significantly down-regulated in NSCLC tissues compared to the normal tissue. In in-vitro study, overexpression of miR-124 in A549 cells suppressed cell migration and invasion activity, decreased expression of vimentin, but increased expression of E-cadherin and induced apoptosis. Luciferase reporter assay ensured that ZEB1 was a direct target of miR-124 and was negatively regulated by miR-124. Overexpression of ZEB1 could reverse the effect of miR-124 Mimic on the migration and invasion of the cells. CONCLUSION: The results suggests that miR-124 inhibits lung cancer cell migration and invasion through suppressing epithelial mesenchymal transition (EMT) and inducing apoptosis of the lung cancer cells. PMID- 27251410 TI - Spontaneous remission of eosinophilic granuloma of the maxilla after incisional biopsy: a case report. AB - BACKGROUND: Langerhans cell histiocytosis (LCH), previously known as Histiocytosis X, is an infrequent disease that congregates a wide spectrum of clinical presentations with variable systemic involvement. Unification of these diseases under only one category is based on the almost identical histopathologic features of the lesions, but the etiology and proper approach for each presentation remains controversial. The localized alternative of Langerhans cell histiocytosis (LLCH), known as Eosinophilic Granuloma (EG) of bone, is the predominant clinical presentation of LCH. The maxilla is involved in 1 % of the head and neck region cases, representing an uncommon condition in this area. CASE PRESENTATION: In this clinical case report, it is described a case of a 16-year old male patient with an asymptomatic osteolytic lesion at first upper left molar apical level, a finding detected on control radiographic images was reported as "Monostotic Eosinophilic granuloma of the maxillary bone", which was later confirmed through an incisional biopsy. A surgical excision was initially planned, but finally it was not performed due to a spontaneous healing of the lesion after the incisional biopsy. CONCLUSIONS: The presented case supports a conservative approach in the management of solitary EG of maxillary and mandibular bone lesions and even supports an expectant attitude in the course of treatment given the possibility of a spontaneous regression after the biopsy, especially in small lesions. PMID- 27251411 TI - Prolonged Tp-e Interval and Tp-e/QT Ratio in Children with Mitral Valve Prolapse. AB - Although it is considered to be a benign condition, previous studies have shown that a subset of patients with mitral valve prolapse (MVP) may be at risk of ventricular arrhythmia and sudden cardiac death (SCD). Previous studies have suggested that the interval between the peak and the end of the T wave (Tp-e) can be used as a marker for the transmural dispersion of repolarization. Increased Tp e interval and Tp-e/QT ratio are associated with ventricular arrhythmias and SCD. The aim of this study was to assess alterations in ventricular repolarization by using the Tp-e interval and Tp-e/QT ratio in children with MVP and to investigate their relationships with the degree of valvular regurgitation. This study prospectively investigated 110 children with MVP and 107 age- and sex-matched healthy control subjects. Tp-e interval, Tp-e/QT ratio, and QT and QTc dispersions were measured from a 12-lead electrocardiogram and compared between groups. QT and QTc dispersions, Tp-e interval, and Tp-e/QTc ratio were found to be significantly higher in patients with MVP. A positive correlation was found between Tp-e/QTc ratio and increase in the degree of mitral regurgitation (MR) (p < 0.05; r = 0.2). However, the degree of MR was not associated with QT, QTc, or Tp-e intervals; QT, QTc, or Tp-e dispersions; or Tp-e/QT ratio (all p values >0.05). Individuals with MVP may be more prone to ventricular arrhythmias due to prolonged QTd, QTcd, and Tp-e interval and increased Tp-e/QT and Tp-e/QTc ratios. Therefore, due to their longer life expectancy, children with MVP should be followed up on regarding life-threatening arrhythmias. PMID- 27251412 TI - Adaption of microbial community during the start-up stage of a thermophilic anaerobic digester treating food waste. AB - A successful start-up enables acceleration of anaerobic digestion (AD) into steady state. The microbial community influences the AD performance during the start-up. To investigate how microbial communities changed during the start-up, microbial dynamics was analyzed via high-throughput sequencing in this study. The results confirmed that the AD was started up within 25 d. Thermophilic methanogens and bacterial members functioning in hydrolysis, acidogenesis, and syntrophic oxidation became predominant during the start-up stage, reflecting a quick adaption of microorganisms to operating conditions. Such predominance also indicated the great contribution of these members to the fast start-up of AD. Redundancy analysis confirmed that the bacterial abundance significantly correlated with AD conditions. The stable ratio of hydrogenotrophic methanogens to aceticlastic methanogens is also important to maintain the stability of the AD process. This work will be helpful to understand the contribution of microbial community to the start-up of AD. PMID- 27251413 TI - Biomaterials for Enhancing CNS Repair. AB - The health of the central nervous system (CNS) does not only rely on the state of the neural cells but also on how various extracellular components organize cellular behaviors into proper tissue functions. Biomaterials have been valuable in restoring or augmenting the roles of extracellular components in the CNS in the event of injury and disease. In this review, we highlight how biomaterials have been enabling tools in important therapeutic strategies involving cell transplantation and drug/protein delivery. We further discuss advances in biomaterial design and applications that can potentially be translated into the CNS to provide unprecedented benefits. PMID- 27251414 TI - Preparation and Characterization of Gelonin-Melittin Fusion Biotoxin for Synergistically Enhanced Anti-Tumor Activity. AB - PURPOSE: To investigate the applicability of fusion biotoxins combining pore forming toxins (PFTs) and ribosome-inactivating proteins (RIPs) for the anti cancer treatment. METHODS: Membrane active PFTs tend to destabilize cell membranes of tumor cells, but lack a warhead inducing significant cause of cell death. Cell-impermeable RIPs possess a powerful warhead, yet not able to enter the tumor cells. To address these challenges for anti-tumor effects, we introduced a fusion strategy of conjugating melittin (a PFT) and gelonin (a type 1 RIP) via chemical and recombinant methods, followed by in vitro assays and in vivo animal studies. RESULTS: In vitro characterization results confirmed that the chimeric gelonin-melittin fusion proteins retained equivalent intrinsic activity to that of unmodified gelonin in inhibiting protein translation. However, chemically conjugated gelonin-melittin (cGel-Mel) and recombinant chimeric gelonin-melittin fusion (rGel-Mel) exhibited greater cell uptake, yielding a significantly enhanced cytotoxic activity over treatment of gelonin, melittin or physical mixture of gelonin and melittin. Remarkably, cGel-Mel and rGel-Mel displayed 32- and 10-fold lower IC50 than gelonin in the cell lines. The superior anti-tumor efficacy of multivalent cGel-Mel to monovalent rGel-Mel suggested that valency could be a crucial factor for the extent of melittin mediated cell uptake. Tumoricidal effects observed from animal studies were in good accordance with our findings from the cellular assays. CONCLUSIONS: This study successfully demonstrated that fusion of biotoxins could provide a simple yet effective way to synergistically augment their anti-tumor activity. PMID- 27251415 TI - Humid Heat Autoclaving of Hybrid Nanoparticles Achieved by Decreased Nanoparticle Concentration and Improved Nanoparticle Stability Using Medium Chain Triglycerides as a Modifier. AB - PURPOSE: Humid heat autoclaving is a facile technique widely used in the sterilization of injections, but the high temperature employed would destroy nanoparticles composed of biodegradable polymers. The aim of this study was to investigate whether incorporation of medium chain triglycerides (MCT) could stabilize nanoparticles composed of poly (ethylene glycol)-b-polycaprolactone (PEG-b-PCL) during autoclaving (121 degrees C, 10 min). METHODS: Polymeric nanoparticles with different MCT contents were prepared by dialysis. Block copolymer degradation was studied by GPC. The critical aggregation concentrations of nanoparticles at different temperatures were determined using pyrene fluorescence. The size, morphology and weight averaged molecular weight of pristine/autoclaved nanoparticles were studied using DLS, TEM and SLS, respectively. Drug loading content and release profile were determined using RP HPLC. RESULTS: The protecting effect of MCT on nanoparticles was dependent on the amount of MCT incorporated. Nanoparticles with high MCT contents, which assumed an emulsion-like morphology, showed reduced block copolymer degradation and particle disassociation after incubation at 100 degrees C for 24 h. Nanoparticles with high MCT content showed the lowest critical aggregation concentration (CAC) under either room temperature or 60 degrees C and the lowest particle concentration among all samples. And the particle size, drug loading content, physical stability and release profile of nanoparticles with high MCT contents remained nearly unchanged after autoclaving. CONCLUSION: Incorporation of high amount of MCT changed the morphology of PEG-b-PCL based nanoparticles to an emulsion-like structure and the nanoparticles prepared could withstand autoclaving due to improved particle stability and decreased particle concentration caused by MCT incorporation. PMID- 27251416 TI - Pediatric Dispersible Tablets: a Modular Approach for Rapid Prototyping. AB - PURPOSE: The design of pediatric formulations is challenging. Solid dosage forms for children have to meet the needs of different ages, e.g. high number of dosing increments and strengths. A modular formulation strategy offering the possibility of rapid prototyping was applied. Different tablet compositions and the resulting tablet characteristics were investigated for dispersible tablets using customized analytical methods. METHODS: Fluid bed granules were blended with extragranular components, and compressed to tablets. Disintegration behavior was studied with a Texture Analyzer and a Tensiometer. RESULTS: Methods for determination of disintegration time and water uptake of tablets were developed with a Texture Analyzer, and a Tensiometer, respectively. Twenty-two different tablet formulations were prepared and analyzed with respect to disintegration time, hardness, friability, and viscosity. Multivariate data analysis revealed a high impact of type and amount of viscosity enhancer on the disintegration behavior of tablets. An optimized formulation was selected with a disintegration time of 24 s. CONCLUSION: Methods providing additional information on the disintegration behavior of dispersible tablets compared to standard pharmacopoeia methods were established. Selecting the right type and level of viscosity enhancer and superdisintegrant was critical for developing pediatric tablets with a disintegration time of less than 30 s but still pleasant mouth feel. PMID- 27251417 TI - Pharmacokinetic considerations in the treatment of hypertension in risperidone medicated patients - thinking of clinically relevant CYP2D6 interactions. AB - BACKGROUND: Treatment of arterial hypertension in patients with severe mental illnesses often results in polypharmacy, potentially leading to drug-drug interactions. The objective of the study was to analyse the in vivo inhibitory potential of two antihypertensive drugs, amlodipine and metoprolol on CYP2D6 catalysed 9-hydroxylation of risperidone (RIS). METHODS: A therapeutic drug monitoring database with plasma concentrations of RIS and 9-hydroxyrisperidone (9 OH-RIS) of 1584 patients was analysed. Three groups were considered; a group of patients receiving RIS without a potentially cytochrome influencing co-medication (control group, R0, n=852), a group co-medicated with amlodipine (RA, n=27) and a group, co-medicated with metoprolol (RM, n=41). Plasma concentrations, concentration-to-dose ratios (C/Ds) of RIS, 9-OH-RIS and the active moiety (AM), as well as the metabolic ratios were computed and compared using the Kruskal Wallis test, the Mann-Whitney U test and the Jonckheere-Terpstra test to determine the means and different patterns of distribution of plasma concentrations as well as the concentration-to-dose ratios. RESULTS: The median daily dosage of RIS did not differ between the groups (p=0.708). No differences were found in median plasma concentrations of RIS, 9-OH-RIS and AM. However, concentration-to-dose ratios for RIS, 9-OH-RIS and AM were significantly higher in the amlodipine group (p=0.025, p=0.048 and p=0.005). In the metoprolol group, the concentration-to-dose ratio for RIS was significantly higher than in the control group (p=0.017), while the C/D for 9-OH-RIS and AM was not. CONCLUSIONS AND LIMITATIONS: Our data show a potential pharmacokinetic interaction, most likely via CYP3A4 between amlodipine and RIS, reflected in significantly different C/Ds for RIS, 9-OH-RIS and AM. Although the interaction did not result in significantly higher plasma levels, changes in C/Ds and their distribution with regard to the median concentrations were observed. PMID- 27251418 TI - Herpetic cranial polyneuritis mimicking brain stem infarction-an atypical presentation of Ramsay Hunt syndrome. AB - An elderly man presented with severe right ear pain and discharge, hoarseness and dysphagia causing significant involuntary weight loss. Extensive investigations by varied specialties only highlighted right vocal cord palsy and right parotid lymphadenitis. Reassessment on transfer to a rehabilitation ward noted clinically subtle right Ramsay Hunt syndrome with multiple lower cranial nerve involvement. We illustrate a case of varicella zoster virus cranial polyneuritis with bulbar symptoms mimicking bulbar stroke, requiring percutaneous endoscopic gastrostomy feeds, with significant clinical and radiological recovery over 1 year. PMID- 27251419 TI - Evaluation of the genotoxicity and cytotoxicity of filling pastes used for pulp therapy on deciduous teeth using the micronucleus test on bone marrow from mice (Mus musculus). AB - Pulp therapy is the last resort for preserving deciduous teeth. However, the genotoxic and cytotoxic effects of many products used in this therapy are not well established. The aim of this study was to use the micronucleus test on bone marrow from mice to evaluate the genotoxic and cytotoxic effects of four filling pastes: zinc oxide, calcium hydroxide P.A., mineral trioxide aggregate and an iodoform paste (iodoform + camphorated + paramonochlorophenol + rifamycin + prednisolone). Male Swiss mice were divided into 4 groups of 10 animals, each exposed to one of the pastes, and were subdivided according to the dilutions tested: 1/10, 1/50, 1/500 and 1/1000 administered intraperitoneally (0.1ml/10g of weight). Cyclophosphamide was the positive control. The negative controls were dimethylsulfoxide and buffered saline solution. Five animals were killed 24h and five 48h after the treatment. The material was processed in accordance with Schmid (1976) and micronuclei were counted in 1000 polychromatic erythrocytes (PCE), under an optical microscope in a blinded test. Cytotoxicity was evaluated using the PCE/normochromatic erythrocyte (NCE) ratio in 200 erythrocytes. The micronucleus analysis results were evaluated using the conditional test for comparing proportions in situations of rare events. Analysis of variance and Tukey's test were used to evaluate the PCE/NCE ratio. There was significantly greater occurrence of micronuclei in the animals treated with iodoform paste at all the dilutions tested, at both sacrifice times. Greater occurrence of micronuclei was observed among the animals treated with zinc oxide and sacrificed 48h after the treatment, at the dilutions 1:50; 1:500 and 1:1000. Calcium hydroxide P.A. and mineral trioxide aggregate did not present any genotoxic or cytotoxic effects. The genotoxicity and cytotoxicity of zinc oxide and iodoform paste revealed here constitute an initial step towards their contraindication, but additional studies will be necessary in order to securely establish the risks involved in their use. PMID- 27251420 TI - Direct spinning of fiber supercapacitor. AB - A direct wet spinning approach is demonstrated for facile and continuous fabrication of a whole fiber supercapacitor using a microfluidic spinneret. The resulting fiber supercapacitor shows good electrochemical properties and possesses high flexibility and mechanical stability. This strategy paves the way for large-scale continuous production of fiber supercapacitors for weavable electronics. PMID- 27251422 TI - Membrane trafficking: The second job of ULKs. PMID- 27251421 TI - The multiple functions of RNA helicases as drivers and regulators of gene expression. AB - RNA helicases comprise the largest family of enzymes involved in the metabolism of mRNAs, the processing and fate of which rely on their packaging into messenger ribonucleoprotein particles (mRNPs). In this Review, we describe how the capacity of some RNA helicases to either remodel or lock the composition of mRNP complexes underlies their pleiotropic functions at different steps of the gene expression process. We illustrate the roles of RNA helicases in coordinating gene expression steps and programmes, and propose that RNA helicases function as molecular drivers and guides of the progression of their mRNA substrates from one RNA processing factory to another, to a productive mRNA pool that leads to protein synthesis or to unproductive mRNA pools that are stored or degraded. PMID- 27251426 TI - Carbon dioxide cleavage across a tungsten-alkylidyne bearing a trianionic pincer type ligand. AB - The cleavage of carbon dioxide by the tungsten alkylidyne [CF3-ONO]W[triple bond, length as m-dash]CCtBu(THF)2 (1) {where CF3-ONO = (MeC6H3[C-(CF3)2O])2N3-}, is reported. Splitting of CO2 yields the tungsten oxo ketene complex [CF3 ONO]W(O){(CH3)3CC[double bond, length as m-dash]C[double bond, length as m dash]O} (6). The proposed pathway occurs through initial cycloaddition of W[triple bond, length as m-dash]C and C[double bond, length as m-dash]O bonds to generate a heterometallacyclobutene, which then rearranges to yield W[triple bond, length as m-dash]O and C[double bond, length as m-dash]C bonds. Complex 6 was characterized by multinuclear NMR, IR, and single crystal X-ray diffraction. PMID- 27251425 TI - Clinical characteristics and prognosis of 272 postterm choriocarcinoma patients at Peking Union Medical College Hospital: a retrospective cohort study. AB - BACKGROUND: The objective of our study was to investigate the clinical characteristics and prognosis of postterm choriocarcinoma patients at Peking Union Medical College Hospital within the past 30 years. METHODS: The clinical characteristics and pertinent follow-up data of 272 patients with postterm choriocarcinoma diagnosed from December 1985 through December 2014 in our hospital were reviewed. The clinical characteristics of two cohorts cut off at 2006 were compared using chi (2) tests. Risk factors of prognosis were estimated by multivariate Cox proportional regression analysis. RESULTS: The most common initial symptom was abnormal uterine bleeding. After individualized treatment 239 patients (87.9 %) achieved complete remission, including 140 patients received initial treatment of 5-fluorouracil-based multidrug chemotherapy. There were almost no statistically significant differences in the clinical characteristics and survival rates between the two cohorts. The results of the multivariate analysis showed that history of resistance to multidrug chemotherapy, liver metastasis and FIGO score greater than 12 were independent risk factors of prognosis. CONCLUSIONS: Postterm choriocarcinoma patients were usually accompanied by several high-risk factors that should received combined chemotherapy to prevent delay in adequate treatment. 5-fluorouracil-based multidrug chemotherapy, which has been applied at PUMCH for several decades, can be an effective initial treatment for postterm choriocarcinoma patients. More emphasis should be placed on those who have history of resistance to multidrug chemotherapy, liver metastasis or a FIGO score greater than 12. PMID- 27251424 TI - miR-200 family promotes podocyte differentiation through repression of RSAD2. AB - Mature podocytes are highly differentiated cells with several characteristic phenotypic features that are involved in the glomerular filtration function. During kidney development, a series of changes of the morphological characteristics and cellular functions may happen in podocytes. The miR-200 family functions in various biological and pathological processes. But the underlying molecular mechanisms of miR-200 family that functions in podocyte differentiation remain poorly understood. Herein is shown that miR-200a, miR-200b and miR-429 are significantly upregulated during the differentiation of podocytes, with highest upregulation of miR-200a. In these cells, restraint of miR-200 family by RNA interference assay revealed a prominent inhibition of cell differentiation. More intriguingly, miR-200 family directly inhibited the radical S-adenosyl methionine domain-containing protein 2 (RASD2) expression. Moreover, further upregulation of RSAD2 combining with restraint of miR-200 family revealed a promotion of podocyte dedifferentiation and proliferation. In addition, the expression of RSAD2 is consistent with that of in vitro podocyte differentiation in prenatal and postnatal mouse kidney, and significantly down-regulated during the kidney development. Together, these findings indicate that miR-200 family may potentially promote podocyte differentiation through repression of RSAD2 expression. Our data also demonstrate a novel role of the antiviral protein RSAD2 as a regulator in cell differentiation. PMID- 27251423 TI - Transcriptional and epigenetic control of brown and beige adipose cell fate and function. AB - White adipocytes store excess energy in the form of triglycerides, whereas brown and beige adipocytes dissipate energy in the form of heat. This thermogenic function relies on the activation of brown and beige adipocyte-specific gene programmes that are coordinately regulated by adipose-selective chromatin architectures and by a set of unique transcriptional and epigenetic regulators. A number of transcriptional and epigenetic regulators are also required for promoting beige adipocyte biogenesis in response to various environmental stimuli. A better understanding of the molecular mechanisms governing the generation and function of brown and beige adipocytes is necessary to allow us to control adipose cell fate and stimulate thermogenesis. This may provide a therapeutic approach for the treatment of obesity and obesity-associated diseases, such as type 2 diabetes. PMID- 27251427 TI - The Effect of an Emollient Containing Urea, Ceramide NP, and Lactate on Skin Barrier Structure and Function in Older People with Dry Skin. AB - Xerosis affects up to 75% of older people and develops as a result of a skin barrier defect. Emollients are widely used to treat xerosis; however, there is limited understanding of the differences between them and their effects on the skin barrier in older people. This study aimed to compare the effect of a commercially available emollient containing 5% urea, ceramide NP and lactate (test emollient) to an alternative emollient without these additives (control emollient) on the properties of the skin barrier in older people. Two cohorts of 21 volunteers aged >60 years with dry skin were recruited. The first applied the test emollient to one forearm and no treatment to the other for 28 days. The second compared the test emollient to the control emollient observing the same parameters. Effects on the skin barrier were determined by measuring skin barrier function, hydration, skin surface pH and by analysing Fourier transform infrared spectra before and after treatment. A third cohort of 6 young adults was recruited to investigate the effect of a single treatment with the test emollient on the molecular structure of the skin barrier at greater depths by employing the tape-stripping technique. The test emollient hydrated the skin to a significantly greater extent and for a longer period of time compared to the control emollient, an effect associated with a significant elevation of carboxylate groups (a marker of natural moisturizing factor content) within the stratum corneum. Furthermore, the test emollient imparted additional benefits to the structure and function of the skin barrier not exhibited by the control emollient. In conclusion, the test emollient addressed the pathological features of xerotic aged skin, supporting its use as first-line therapy for xerotic skin conditions in this population. PMID- 27251428 TI - Repeated Neonatal Sevoflurane Exposure-Induced Developmental Delays of Parvalbumin Interneurons and Cognitive Impairments Are Reversed by Environmental Enrichment. AB - Parvalbumin (PV) interneurons are critically involved in the cognitive processes. Based on prior investigations that environmental enrichment reverses impaired cognition after anesthetic exposure, we proposed that environmental enrichment protects PV interneurons and thereby improves sevoflurane-induced cognitive impairments. Six-day-old C57BL/6 male mice were exposed to 3 % sevoflurane or 30 % oxygen/air 2 h daily for 3 days from postnatal day 6 (P6) to P8. The mice were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or a standard environment. Western blotting and immunofluorescence were used for determining PV expression in the prefrontal cortex and hippocampus. In another set of experiments, cognitive tests were assessed by the open field test (P41), Morris water maze test (P54-60), and fear conditioning tests (P42-43 and P89-90). Exposure of neonatal mice to sevoflurane resulted in a reduced freezing response in the contextual test at P43 but not P90. The PV expression in these mice was decreased at P9, P14, P28, and P42, but not at >=P60. No colocalization of caspase-3 and 5-bromo-2-deoxyuridine or caspase-3 and PV was observed, suggesting that caspase-independent pathways may be involved in the mediation of sevoflurane induced down-regulation of PV. The sevoflurane-exposed mice that were placed in an enriched environment exhibited normal behavior and had PV interneurons that did not differ from those in the control mice at P42-43. Neonatal sevoflurane exposure induces a reduced freezing response in the contextual test at P43 and developmental delays in PV interneurons in the prefrontal cortex and hippocampus. Placement of the sevoflurane-exposed mice in an enriched environment can prevent these abnormalities. PMID- 27251429 TI - Erratum to: Different expression of beta subunits of the KCa1.1 channel by invasive and non-invasive human fibroblast-like synoviocytes. PMID- 27251430 TI - Monitoring the appositions of posterior graft-host junctions with anterior segment optical coherence tomogram after penetrating keratoplasty. AB - This study aimed to monitor the graft-host junction's (GHJ's) apposition with anterior segment optical coherence tomogram after penetrating keratoplasty (PK) and correlate the analysis with the preoperative diagnosis. Fifty-one eyes of 50 patients with various preoperative diagnosis of adherent leucoma, pseudophakic bullous keratopathy, corneal opacity or scarring, graft failure, corneal dystrophy and anterior staphyloma, who underwent PK for optical purposes were reviewed retrospectively. Based on the age, the patients were divided into groups 1 and II: those aged <=40 and >40 years, respectively. Anterior segment optical coherence tomography was done for all these eyes to evaluate the posterior graft host junction. All graft-host junction patterns were classified as well apposed, and malapposed with various components like hill, gap, step and tag. The comparisons of various clinical parameters were done for the various malapposed junction groups (hill, gap, step and tag). A total of 408 graft-host junction cross sections of 51 eyes were analysed. Amongst them 70 (17.15 %) sections were well apposed, and 338 (82.84 %) were malapposed. Most frequent type of malapposition was hill: 164 sections (40.19 %) followed by step: 139 sections (34.06 %). The distribution of graft-host junction alignment patterns varied amongst all the indications. Patients with preoperative diagnosis of adherent leucoma and corneal dystrophy had predominantly steps pattern in 65 (40.62 %) and 12 (75 %) sections, respectively. Hill pattern was seen predominantly in PBK, corneal opacity, graft failure and anterior staphyloma in 55 (42.96 %), 16 (40 %), 22 (45.83 %) and 8 (50 %) sections, respectively. Comparisons of various clinical characteristics like intraocular pressure, central corneal thickness, best-corrected visual acuity, astigmatism and size of graft with the various malapposed patterns showed significant differences in best-corrected visual acuity and keratometric astigmatism in the hill pattern of malapposition group with p values of .004 and .053, respectively, using independent T test. Posterior graft-host junction analysis with anterior segment optical coherence tomography is very important for post penetrating keratoplasty management. The posterior wound profile differed according to the indications of penetrating keratoplasty. Best-corrected visual acuity and keratometric astigmatism showed significant difference with the malapposition hill (pattern). PMID- 27251432 TI - Tetramethyl-6-carboxyrhodamine quenching-based aptasensing platform for aflatoxin B1: Analytical performance comparison of two aptamers. AB - In this study, a simple TAMRA (tetramethyl-6-carboxyrhodamine) quenching-based aptasensing platform was designed for the detection of aflatoxin B1 (AFB1). Here, we compared the analytical performance of two aptamer sequences: seqA and seqB. The AFB1 detection was based on the interactions of FAM (carboxyfluorescein) labeled aptamer with TAMRA-labeled DNA complementary strand in the presence and absence of target analyte. Under optimized experimental conditions, TAMRA-labeled strand quenched the fluorescence response of FAM-labeled aptamer due to the noncovalent interaction between the two DNA strands. The binding of AFB1 induced the complex formation and weakened the interaction between FAM-labeled aptamer and TAMRA-labeled complementary strand, resulting in the fluorescence recovery. By using this principle concept, an assay was constructed for the detection of AFB1. The method exhibited good sensitivity, good selectivity with a limit of detection of 0.2 ng ml(-1), and a wide linear range from 0.25 to 32 ng ml(-1). For real sample application, the aptasensors were tested in beer and wine samples, with good recovery rates obtained for AFB1 detection. PMID- 27251433 TI - Semi-automated microplate monitoring of protein polymerization and aggregation. AB - Static light scattering (SLS) is a commonly used technique for monitoring dynamics of high molecular weight protein complexes such as protein oligomers or aggregates. However, traditional methods are limited to testing a single condition and typically require large amounts of protein and specialized equipment. We show that a standard microplate reader can be used to characterize the molecular dynamics of different types of protein complexes, with the multiple advantages of microscale experimental volumes, semi-automated protocols and highly parallel processing. PMID- 27251431 TI - Hallmarks of cancer and AU-rich elements. AB - Post-transcriptional control of gene expression is aberrant in cancer cells. Sustained stabilization and enhanced translation of specific mRNAs are features of tumor cells. AU-rich elements (AREs), cis-acting mRNA decay determinants, play a major role in the posttranscriptional regulation of many genes involved in cancer processes. This review discusses the role of aberrant ARE-mediated posttranscriptional processes in each of the hallmarks of cancer, including sustained cellular growth, resistance to apoptosis, angiogenesis, invasion, and metastasis. WIREs RNA 2017, 8:e1368. doi: 10.1002/wrna.1368 For further resources related to this article, please visit the WIREs website. PMID- 27251434 TI - Exciton circular dichroism couplet arising from nitrile-derivatized aromatic residues as a structural probe of proteins. AB - Exciton coupling between two chromophores can produce a circular dichroism (CD) couplet that depends on their separation distance, among other factors. Therefore, exciton CD signals arising from aromatic sidechains, especially those of tryptophan (Trp), have been used in various protein conformational studies. However, the long-wavelength component of the commonly used CD couplet produced by a pair of Trp residues is typically located around 230 nm, thereby overlapping significantly with the protein backbone CD signal. This overlap often prevents a direct and quantitative assessment of the Trp CD couplet in question without further spectral analysis. Here, we show that this inconvenience can be alleviated by using a derivative of Trp, 5-cyanotryptophan (TrpCN), as the chromophore. Specifically, through studying a series of peptides that fold into either alpha-helical or beta-hairpin conformations, we demonstrate that in comparison with the Trp CD couplet, that arising from two TrpCN residues not only is significantly red-shifted but also becomes more intense due to the larger extinction coefficient of the underlying electronic transition. In addition, we show that a pair of p-cyanophenylalanines (PheCN) or a PheCN-TrpCN pair can also produce a distinct exciton CD couplet that can be useful in monitoring conformational changes in proteins. PMID- 27251435 TI - Epidermal multinucleated keratinocytes: a histopathologic clue to dermatitis artefacta. AB - Dermatitis artefacta is a psycho-cutaneous disorder characterized by self inflicted cutaneous injuries, often in association with an underlying psychiatric disorder or as a response to external stressors. Cutaneous lesions suggestive of dermatitis artefacta are dependent on the means of injury and thus may be morphologically variable, but typically have geometric shapes, spare hard-to reach anatomic areas, and are present in variable stages of evolution at any specific time. Although a dermatologist may be suspicious of dermatitis artefacta in a given patient, making a definitive diagnosis is extremely challenging. Patients often clinically evade questioning and deny creating skin lesions, and histopathologic evaluation of lesional biopsies usually reveals non-specific epidermal and dermal changes and inflammation. Thus, identification of clues that lend support to a diagnosis of dermatitis artefacta would be welcomed by both clinicians and pathologists. Here we present a case of dermatitis artefacta with a unique, yet previously reported, histopathological finding of multinucleated keratinocytes within the epidermis. Although probably uncommon and dependent on the etiology of cutaneous injury, we believe this finding is important for dermatopathologists to be aware of as a potential diagnostic clue when evaluating biopsies in patients suspected to have dermatitis artefacta. PMID- 27251436 TI - Depression and Engagement in Care Among Newly Diagnosed HIV-Infected Adults in Johannesburg, South Africa. AB - Delayed engagement in HIV care threatens the success of HIV treatment programs in sub-Saharan Africa and may be influenced by depression. We examined the relationship between depression prior to HIV diagnosis and engagement in HIV care at a primary care clinic in Johannesburg, South Africa. We screened 1683 patients for depression prior to HIV testing using the Patient Health Questionnaire-9. Among patients who tested positive for HIV we assessed linkage to HIV care, defined as obtaining a CD4 count within 3 months. Among those who linked to care and were eligible for ART, we assessed ART initiation within 3 months. Multivariable Poisson regression with a robust variance estimator was used to assess the association between depression and linkage to care or ART initiation. The prevalence of HIV was 26 % (n = 340). Among HIV-infected participants, the prevalence of depression was 30 %. The proportion of linkage to care was 80 % among depressed patients and 73 % among patients who were not depressed (risk ratio 1.08; 95 % confidence interval 0.96, 1.23). Of the participants who linked to care, 81 % initiated ART within 3 months in both depressed and not depressed groups (risk ratio 0.99; 95 % confidence interval 0.86, 1.15). Depression was not associated with engagement in HIV care in this South African primary care setting. Our unexpected findings suggest that some depressed HIV-infected patients might be more likely to engage in care than their counterparts without depression, and highlight the complex relationship between depression and HIV infection. These findings have led us to propose a new framework relating HIV infection, depression, and the population under study. PMID- 27251439 TI - Human adipocytes from the subcutaneous superficial layer have greater adipogenic potential and lower PPAR-gamma DNA methylation levels than deep layer adipocytes. AB - Human subcutaneous fat tissue consists of two layers, superficial adipose tissue (SAT) and deep adipose tissue (DAT). Some recent reports suggest that a disproportionate accumulation of DAT is related to obesity-associated metabolic complications. However, the differences in adipocyte function between SAT and DAT are unclear. To clarify the differences in human adipocyte characteristics between SAT and DAT, human ceiling culture-derived proliferative adipocytes (ccdPAs) were primary cultured from SAT and DAT of three lean female patients. Differences in adipogenic differentiation potential and sensitivity to exogenous adipogenic factors were examined. Epigenetic modification of the CpG island DNA methylation levels of genes related to adipogenesis was measured. In histological analyses, the mean adipocyte size in SAT was significantly larger than that in DAT (8,741 +/- 416 vs. 7,732 +/- 213 MUm(2), P < 0.05). Primary cultured adipocytes from SAT showed significantly greater adipogenesis than did those of DAT. Sensitivity to partial adipogenic stimulation was significantly different between ccdPAs of SAT and DAT. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) protein expression and leptin protein secretion from ccdPAs were significantly higher in SAT than DAT. DNA methylation levels of PPAR-gamma were significantly lower in ccdPAs of SAT than DAT. Adipocyte size was larger in SAT than DAT in vivo. This is consistent with the findings of an in vitro study that, compared with ccdPAs in DAT, ccdPAs in SAT have higher adipogenic potential and lower DNA methylation levels of PPAR-gamma. PMID- 27251438 TI - Role of the tryptophan residues in proton-coupled folate transporter (PCFT SLC46A1) function. AB - The proton-coupled folate transporter (PCFT) mediates folate absorption across the brush-border membrane of the proximal small intestine and is required for folate transport across the choroid plexus into the cerebrospinal fluid. In this study, the functional role and accessibility of the seven PCFT Trp residues were assessed by the substituted-cysteine accessibility method. Six Trp residues at a lipid-aqueous interface tolerated Cys substitution in terms of protein stability and function. W85C, W202C, and W213C were accessible to N-biotinyl aminoethylmethanethiosulfonate; W48C and W299C were accessible only after treatment with dithiotreitol (DTT), consistent with modification of these residues by an endogenous thiol-reacting molecule and their extracellular location. Neither W107C nor W333C was accessible (even after DTT) consistent with their cytoplasmic orientation. Biotinylation was blocked by pemetrexed only for the W48C (after DTT), W85C, W202C residues. Function was impaired only for the W299C PCFT mutant located in the 4th external loop between the 7th and 8th transmembrane helices. Despite its aqueous location, function could only be fully preserved with Phe and, to a lesser extent, Ala substitutions. There was a 6.5 fold decrease in the pemetrexed influx Vmax and a 3.5- and 6-fold decrease in the influx Kt and Ki, respectively, for the W299S PCFT. The data indicate that the hydrophobicity of the W299 residue is important for function suggesting that during the transport cycle this residue interacts with the lipid membrane thereby impacting on the oscillation of the carrier and, indirectly, on the folate binding pocket. PMID- 27251437 TI - Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production. AB - Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor kappaB (NF-kappaB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1beta could trigger NO production in MSCs and exert anti mycobacterial activity via NF-kappaB signaling pathway. Neutralization of interleukin-1beta in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection. PMID- 27251440 TI - Quinones Derived from Polychlorinated Biphenyls Induce ROS-Dependent Autophagy by Evoking an Autophagic Flux and Inhibition of mTOR/p70S6k. AB - Autophagy is a "self-eating" destructive process that eliminates damaged organelles to maintain cellular homeostasis. Polychlorinated biphenyls (PCBs) are one of the most infamous industrial pollutants, which are ubiquitous in nature. In the present study, we found that an active, quinone-type PCB metabolite (PCB29 pQ) treatment causes an autophagic response through mTOR/p70S6k inhibition in HepG2 and MDA-MB-231 cells. Furthermore, our data suggested that PCB29-pQ enhances autophagosome formation through autophagic vacuole (AV) biogenesis, which evokes autophagic flux and induces AV-lysosome colocalization. The inhibition of autophagy enhanced PCB29-pQ-caused cytotoxicity, suggesting that autophagy serves as pro-survival machinery that plays a protective role in the early stage of PCB29-pQ-induced insult. However, higher concentration of PCB29-pQ exposure (>5 MUM) caused autophagic cell death, which implied a shift from "pro survival" to "pro-death" upon autophagic signaling. N-Acetylcysteine suppressed PCB29-pQ-induced autophagy and cytotoxicity, suggesting that ROS plays an important role in the regulation of PCB29-pQ-induced autophagy. Because autophagy shows significant implications in various human diseases and conditions, our current study provides a new mechanism for PCB-associated toxicity. PMID- 27251441 TI - Stereotactic Ablative Radiotherapy for Oligometastatic Disease: a Treatment in Search of Evidence - a Response. PMID- 27251442 TI - Disparities in adversity among children with autism spectrum disorder: a population-based study. AB - AIM: People with autism spectrum disorders (ASDs) experience disparities in health. An important but overlooked risk factor for health disparities in the ASD population is adverse childhood experiences (ACEs). The purpose of this study was to identify the prevalence of ACEs among families of children with and without ASD, using a population-based sample. METHOD: Data from the 2011 to 2012 National Survey of Child Health were analyzed to estimate prevalence of ACEs among families of children with and without ASD, age 3 to 17 years (ASD=1611; estimated population=1 165 34). The child's ASD status was obtained from parent report; ACEs were assessed with the modified Adverse Childhood Experiences Scale. Bivariate and multinomial logistic regression analyses were utilized to investigate the relationship between ACEs and childhood ASD status. RESULTS: ASD status among children was significantly and independently associated with higher probability of reporting one to three ACEs (adjusted relative risk ratio [aRRR] 1.53; 95% CI: 1.16-2.0; p<0.010) and four or more ACEs (aRRR 1.99; 95% CI: 1.35 2.91; p<0.010). INTERPRETATION: Children with ASD may experience a greater number of family and neighborhood adversities, potentially compromising their chances for optimal physical and behavioral health outcomes. Assessment and reduction of ACEs among families of young people with ASD could potentially contribute to the reduction of population health disparities. PMID- 27251443 TI - Transcription of a novel P450 gene varies with some factors (pollutant exposure, temperature, time, and body region) in a marine oligochaete (Thalassodrilides sp.). AB - Cytochrome P450 (CYP) enzymes play important roles in the metabolism of exogenous compounds such as polycyclic aromatic hydrocarbons (PAHs). A novel, full-length CYP gene (CYP4V30) was identified in the oligochaete Thalassodrilides sp. CYP4V30 mRNA expression was studied in worms exposed to PAH-polluted (Sigma16PAHs; 37441ng/g dry weight) or unpolluted (Sigma16PAHs; 19ng/g dry weight) sediment. CYP4V30 expression was much higher in worms exposed to contaminated sediments than in those exposed to unpolluted sediments at some temperatures (20 and 25 degrees C) and exposure durations (11-fold increase at 20 degrees C, 10-day exposure), but not at 15 degrees C or other exposure durations (P<0.05). CYP4V30 mRNA expression was higher in the middle of the body than in the posterior (P<0.05). The variation in transcriptional response with exposure time, temperature, and body region indicates that these factors should be considered when monitoring marine sediment pollution. PMID- 27251444 TI - Geogenic metal mobility in a coastal inlet impacted by cannery discharge, Magdalena Bay, Baja California Sur, Mexico. AB - Magdalena Bay is an important habitat for marine organisms, some of which have been the subject of metal bioaccumulation studies. Cannery waste is discharged into the bay providing a plausible source of contamination but this study finds that some metals occur geogenically. Bay sediments and rocks (n=59) were analyzed for total metals and clustered (HCA) into two distinct groups with PCA indicating concentrations of Cr, Cu, Mn, and Ni influenced samples near ophiolite outcrops, which reported some metal concentrations exceeding averages in the crust by an order of magnitude (up to 4450ppm Cr and 1269ppm Ni). Metals at the cannery are rarely elevated above crustal averages except Zn (max. 160ppm), however, acid extracted Zn was below recommended sediment quality guidelines in contrast to 80% of ophiolitic samples reporting Ni extractability exceeding such guidelines. This study raises awareness of geogenic metals when considering sources of contamination in marine environments. PMID- 27251445 TI - Cloning, purification, crystallization and X-ray crystallographic analysis of the periplasmic sensing domain of Pseudomonas fluorescens chemotactic transducer of amino acids type A (CtaA). AB - Chemotaxis towards nutrients plays a crucial role in root colonization by Pseudomonas fluorescens. The P. fluorescens chemotactic transducer of amino acids type A (CtaA) mediates movement towards amino acids present in root exudates. In this study, the periplasmic sensory domain of CtaA has been crystallized by the hanging-drop vapor diffusion method using ammonium sulfate as a precipitating agent. A complete data set was collected to 1.9 A resolution using cryocooling conditions and synchrotron radiation. The crystals belong to space group I222 or I212121, with unit-cell parameters a = 67.2, b = 76.0, c = 113.3 A. This is an important step towards elucidation of the structural basis of how CtaA recognizes its signal molecules and transduces the signal across the membrane. PMID- 27251446 TI - Predictive biomarkers for targeted and cytotoxic agents in gastric cancer for personalized medicine. AB - Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer. The treatment of GC remains challenging as the outcomes achieved with surgery alone or adjuvant or neoadjuvant chemotherapy and radiotherapy are relatively poor. New treatment strategies are emerging and are being tested in solid tumors including GC. Over the past few years, the treatment of metastatic colorectal cancer (CRC) has made great advances, but strategies to manage GC have improved little. Multiple drug resistance is common in GC chemotherapy and targeted therapy; some patients appear to receive treatment that is suboptimal or even inefficacious. Unfortunately, there are few validated predictive biomarkers to guide the tailored treatment of GC. ToGA and AVAGAST are two phase III trials that tested the efficacy and safety of targeted agents in advanced gastric cancer (AGC), and results clearly indicated that patients need to be selected and that targeted agents are the best hope for better results. This review aims to provide an overview of potential predictive biomarkers for cytotoxic and targeted agents in GC. PMID- 27251448 TI - The Great Reduction of a Carbon Nanotube's Mechanical Performance by a Few Topological Defects. AB - It is widely believed that carbon nanotubes (CNTs) can be employed to produce superstrong materials with tensile strengths of up to 50 GPa. Numerous efforts have, however, led to CNT fibers with maximum strengths of only a few GPa. Here we report that, due to different mechanical responses to the tensile loading of disclination topological defects in the CNT walls, a few of these topological defects are able to greatly decrease the strength of the CNTs, by up to an order of magnitude. This study reveals that even nearly perfect CNTs cannot be used to build exceptionally strong materials, and therefore synthesizing flawless CNTs is essential for utilizing the ideal strength of CNTs. PMID- 27251447 TI - The dynamic transcriptional and translational landscape of the model antibiotic producer Streptomyces coelicolor A3(2). AB - Individual Streptomyces species have the genetic potential to produce a diverse array of natural products of commercial, medical and veterinary interest. However, these products are often not detectable under laboratory culture conditions. To harness their full biosynthetic potential, it is important to develop a detailed understanding of the regulatory networks that orchestrate their metabolism. Here we integrate nucleotide resolution genome-scale measurements of the transcriptome and translatome of Streptomyces coelicolor, the model antibiotic-producing actinomycete. Our systematic study determines 3,570 transcription start sites and identifies 230 small RNAs and a considerable proportion (~21%) of leaderless mRNAs; this enables deduction of genome-wide promoter architecture. Ribosome profiling reveals that the translation efficiency of secondary metabolic genes is negatively correlated with transcription and that several key antibiotic regulatory genes are translationally induced at transition growth phase. These findings might facilitate the design of new approaches to antibiotic discovery and development. PMID- 27251449 TI - Highly Sensitive Measurement of Inositol 1,4,5-Trisphosphate by Using a New Fluorescent Ligand and Ligand Binding Domain Combination. AB - Based on the results of our previous adenophostin A structure-activity relationship studies, two fluorescent inositol 1,4,5-trisphosphate (IP3 ) receptor ligands, fluorescent adenophostin A (FADA) and fluorescent low-affinity ligand (FLL), were designed. Binding of the fluorescent ligands to the fluorescent IP3 sensor in protein-expressing cells caused FRET. This principle was extended to a cell-free assay system by using the fluorescent IP3 sensor bound to agarose beads. The effect of FLL on the FRET signal was reduced by subsequent addition of IP3 . The IC50 values of IP3 on the FRET signals were 139.7 and 352.1 nm for 30 and 100 nm FLL, respectively. This method allowed quantitative measurement of IP3 concentrations below 10 nm and was applied to measure cytosolic IP3 concentrations in COS-7 cells and to examine the potency of synthesized adenophostin A analogues. PMID- 27251450 TI - GC-MS-Based Metabolome and Metabolite Regulation in Serum-Resistant Streptococcus agalactiae. AB - Streptococcus agalactiae causes severe systemic infections in human and fish. In the present study, we established a pathogen-plasma interaction model by which we explored how S. agalactiae evaded serum-mediated killing. We found that S. agalactiae grew faster in the presence of yellow grouper plasma than in the absence of the plasma, indicating S. agalactiae evolved a way of evading the fish immune system. To determine the events underlying this phenotype, we applied GC MS-based metabolomics approaches to identify differential metabolomes between S. agalactiae cultured with and without yellow grouper plasma. Through bioinformatics analysis, decreased malic acid and increased adenosine were identified as the most crucial metabolites that distinguish the two groups. Meanwhile, they presented with decreased TCA cycle and elevated purine metabolism, respectively. Finally, exogenous malic acid and adenosine were used to reprogram the plasma-resistant metabolome, leading to elevated and decreased susceptibility to the plasma, respectively. Therefore, our findings reveal for the first time that S. agalactiae utilizes a metabolic trick to respond to plasma killing as a result of serum resistance, which may be reverted or enhanced by exogenous malic acid and adenosine, respectively, suggesting that the metabolic trick can be regulated by metabolites. PMID- 27251451 TI - Association of ideal cardiovascular health metrics and cognitive functioning: the APAC study. AB - BACKGROUND AND PURPOSE: Previous studies have demonstrated that the components of ideal cardiovascular health (CVH) metrics are related to dementia. This study aimed to investigate the overall effects of ideal CVH metrics on cognitive functioning. METHODS: Information was collected on the seven ideal CVH metrics (smoking, body mass index, dietary intake, physical activity, blood pressure, total cholesterol and fasting blood glucose) from the Asymptomatic Polyvascular Abnormalities Community study, and cognitive functioning was assessed by the score of the Mini-Mental State Examination (MMSE). Multivariate logistic regression and linear regression models were used to assess the relationships between ideal CVH metrics and cognitive functioning. RESULTS: A total of 3260 (56.7% men) patients were included in this study. After adjusting for potential confounding factors, the associations between the number or score of ideal CVH metrics and cognitive impairment remained significant [odds ratio (OR) (95% confidence interval) 0.773 (0.664-0.928) and 0.904 (0.831-0.983), respectively]. In addition, there were significant linear relationships between the number or score of CVH metrics and the score of the MMSE (beta = 0.211 and 0.134 respectively, P < 0.001). CONCLUSIONS: A clear inverse association was observed between the number or score of ideal CVH metrics and cognitive impairment in a Chinese population, supporting the importance of ideal CVH metrics in prevention of dementia. PMID- 27251452 TI - Luminescence mechanisms of defective ZnO nanoparticles. AB - ZnO nanoparticles (NPs) synthesized by pulsed laser ablation (PLAL) of a zinc plate in deionized water were investigated by time-resolved photoluminescence (PL) and complementary techniques (TEM, AFM, MURaman). HRTEM images show that PLAL produces crystalline ZnO NPs in wurtzite structure with a slightly distorted lattice parameter a. Consistently, optical spectra show the typical absorption edge of wurtzite ZnO (Eg = 3.38 eV) and the related excitonic PL peaked at 3.32 eV with a subnanosecond lifetime. ZnO NPs display a further PL peaking at 2.2 eV related to defects, which shows a power law decay kinetics. Thermal annealing in O2 and in a He atmosphere produces a reduction of the A1(LO) Raman mode at 565 cm(-1) associated with oxygen vacancies, accompanied by a decrease of defect related emission at 2.2 eV. Based on our experimental results the emission at 2.2 eV is proposed to originate from a photo-generated hole in the valence band recombining with an electron deeply trapped in a singly ionized oxygen vacancy. This investigation clarifies important aspects of the photophysics of ZnO NPs and indicates that ZnO emission can be controlled by thermal annealing, which is important in view of optoelectronic applications. PMID- 27251453 TI - Synchronized Nasal Intermittent Positive Pressure Ventilation of the Newborn: Technical Issues and Clinical Results. AB - Although mechanical ventilation via an endotracheal tube has undoubtedly led to improvement in neonatal survival in the last 40 years, the prolonged use of this technique may predispose the infant to development of many possible complications including bronchopulmonary dysplasia. Avoiding mechanical ventilation is thought to be a critical goal, and different modes of noninvasive respiratory support beyond nasal continuous positive airway pressure, such as nasal intermittent positive pressure ventilation and synchronized nasal intermittent positive pressure ventilation, are also available and may reduce intubation rate. Several trials have demonstrated that the newer modes of noninvasive ventilation are more effective than nasal continuous positive airway pressure in reducing extubation failure and may also be more helpful as modes of primary support to treat respiratory distress syndrome after surfactant and for treatment of apnea of prematurity. With synchronized noninvasive ventilation, these benefits are more consistent, and different modes of synchronization have been reported. Although flow-triggering is the most common mode of synchronization, this technique is not reliable for noninvasive ventilation in neonates because it is affected by variable leaks at the mouth and nose. This review discusses the mechanisms of action, benefits and limitations of noninvasive ventilation, describes the different modes of synchronization and analyzes the technical characteristics, properties and clinical results of a flow-sensor expressly developed for synchronized noninvasive ventilation. PMID- 27251454 TI - "Carbon monoxide poisoning"-triggered cardiomyopathy and takotsubo syndrome. PMID- 27251455 TI - Prevalence and progression of pectinate ligament dysplasia in the Welsh springer spaniel. AB - OBJECTIVES: To determine the prevalence of pectinate ligament dysplasia in a large group of Welsh springer spaniels; to investigate associations between pectinate ligament dysplasia and age, sex and intraocular pressure and between intraocular pressure and age and sex; and to investigate progression of pectinate ligament dysplasia in individual dogs. METHODS: In a prospective study, gonioscopy was performed in both eyes of 227 Welsh springer spaniels and intraocular pressure measured by rebound tonometry. Eyes were classified as "unaffected" if 0% of the iridocorneal angle was affected with pectinate ligament dysplasia (grade 0), "mildly affected" if <20% was affected (grade 1), "moderately affected" if 20 to 90% was affected (grade 2) and "severely affected" if >90% was affected (grade 3). In a retrospective study, progression of pectinate ligament dysplasia over time was investigated for 65 dogs. RESULTS: One hundred and thirty-nine of 227 dogs (61.2%) were affected by pectinate ligament dysplasia (grades 1 to 3) and 82/227 (36.2%) were moderately or severely affected. There was a significant association between pectinate ligament dysplasia and age. There were no associations between pectinate ligament dysplasia and intraocular pressure or pectinate ligament dysplasia and sex. Thirty-five of 65 dogs (53.8%) demonstrated progression of pectinate ligament dysplasia. CLINICAL SIGNIFICANCE: Prevalence of pectinate ligament dysplasia was high despite widespread screening and selection against the condition. Our data indicate that gonioscopic features of pectinate ligament dysplasia can progress in the Welsh springer spaniel. Dogs deemed unaffected at an early age may subsequently be diagnosed with pectinate ligament dysplasia. PMID- 27251457 TI - Highly selective uptake of carbon dioxide on the zeolite |Na10.2KCs0.8|-LTA- a possible sorbent for biogas upgrading. AB - The|Na10.2KCs0.8|8[Al12Si12O48]8(Fm3[combining macron]c)-LTA zeolite adsorbs CO2 over-CH4 with a high selectivity (over 1500). The uptake of carbon dioxide is also high (3.31 mmol g(-1), 293 K, 101 kPa). This form of zeolite A is a very promising adsorbent for applications such as biogas upgrading, where keeping the adsorption of methane to a minimum is crucial. PMID- 27251456 TI - Antimicrobial activity, improved cell selectivity and mode of action of short PMAP-36-derived peptides against bacteria and Candida. AB - Antimicrobial peptides (AMPs) have recently attracted a great deal of attention as promising antibiotic candidates, but some obstacles such as toxicity and high synthesis cost must be addressed before developing them further. For developing short peptides with improved cell selectivity, we designed a series of modified PMAP-36 analogues. Antimicrobial assays showed that decreasing chain length in a certain range retained the high antimicrobial activity of the parental peptide and reduced hemolysis. The 18-mer peptide RI18 exhibited excellent antimicrobial activity against both bacteria and fungi, and its hemolytic activity was observably lower than PMAP-36 and melittin. The selectivity indexes of RI18 against bacteria and fungi were improved approximately 19-fold and 108-fold, respectively, compared to PMAP-36. In addition, serum did not affect the antibacterial activity of RI18 against E. coli but inhibited the antifungal efficiency against C. albicans. Flow cytometry and electron microscopy observation revealed that RI18 killed microbial cells primarily by damaging membrane integrity, leading to whole cell lysis. Taken together, these results suggest that RI18 has potential for further therapeutic research against frequently-encountered bacteria and fungi. Meanwhile, modification of AMPs is a promising strategy for developing novel antimicrobials to overcome drug resistance. PMID- 27251458 TI - European drug agency recommends limiting colistin use in animals to cut resistance in patients. PMID- 27251459 TI - Improved long-term antiretroviral treatment outcomes amongst patients receiving community-based adherence support in South Africa. AB - Retaining high levels of patients in care who are virally suppressed over long treatment periods has been an important challenge for antiretroviral treatment (ART) programmes in sub-Saharan Africa, the region having the highest HIV burden globally. Clinic-linked community-based adherence support (CBAS) programmes provide home-based adherence and psychosocial support for ART patients. However, there is little evidence of their longer-term impact. This study assessed the effectiveness of CBAS after eight years of ART. CBAS workers are lay healthcare personnel providing regular adherence and psychosocial support for ART patients and their households through home visits addressing household challenges affecting adherence. A multicentre cohort study using routinely collected data was undertaken at six public ART sites in a high HIV-prevalence South African district. Patient retention, loss to follow-up (LTFU), viral suppression and CD4 cell restoration were compared between patients with and without CBAS, using competing-risks regression, linear mixed models and log-binomial regression. 3861 patients were included, of whom 1616 (41.9%) received CBAS. Over 14,792 patient years of observation, the cumulative incidence of LTFU was 37.3% and 46.2% amongst patients with and without CBAS, respectively, following 8 years of ART; adjusted subhazard ratio (CBAS vs. no CBAS) = 0.74 (95% CI: 0.66-0.84; P < .0001). Amongst patients on ART for 6.5-8 years, proportions not achieving viral suppression were 11.4% and 19.4% in patients with and without CBAS, respectively; adjusted risk ratio = 0.47 (95% CI: 0.26-0.86; P = .015). Annual CD4 cell increases from baseline were 62.8 cells/uL/year and 51.5 cells/uL/year amongst patients with and without CBAS, respectively, after 6.5 years or more (P = .034). After adjustment, annual CD4 cell recovery was 15.1 cells/uL/year (95% CI: 2.7 27.6) greater in CBAS patients (P = .017). ART patients who received CBAS had improved long-term patient retention, viral suppression and immunological restoration. CBAS is an intervention that can improve longer-term ART programme outcomes in resource-limited settings. PMID- 27251460 TI - Radio frequency spectral characterization and model parameters extraction of high Q optical resonators. AB - A microwave domain characterization approach is proposed to determine the properties of high quality factor optical resonators. This approach features a very high precision in frequency and aims to acquire a full knowledge of the complex transfer function (amplitude and phase) characterizing an optical resonator using a microwave vector network analyzer. It is able to discriminate between the different coupling regimes, from the under-coupling to the selective amplification, and it is used together with a model from which the main resonator parameters are extracted, i.e. coupling factor, intrinsic losses, phase slope, intrinsic and external quality factor. PMID- 27251461 TI - Influenza vaccination for healthcare workers who care for people aged 60 or older living in long-term care institutions. AB - BACKGROUND: A systematic review found that 3% of working adults who had received influenza vaccine and 5% of those who were unvaccinated had laboratory-proven influenza per season; in healthcare workers (HCWs) these percentages were 5% and 8% respectively. Healthcare workers may transmit influenza to patients. OBJECTIVES: To identify all randomised controlled trials (RCTs) and non-RCTs assessing the effects of vaccinating healthcare workers on the incidence of laboratory-proven influenza, pneumonia, death from pneumonia and admission to hospital for respiratory illness in those aged 60 years or older resident in long term care institutions (LTCIs). SEARCH METHODS: We searched CENTRAL (2015, Issue 9), MEDLINE (1966 to October week 3, 2015), EMBASE (1974 to October 2015) and Web of Science (2006 to October 2015), but Biological Abstracts only from 1969 to March 2013 and Science Citation Index-Expanded from 1974 to March 2013 due to lack of institutional access in 2015. SELECTION CRITERIA: Randomised controlled trials (RCTs) and non-RCTs of influenza vaccination of healthcare workers caring for individuals aged 60 years or older in LTCIs and the incidence of laboratory proven influenza and its complications (lower respiratory tract infection, or hospitalisation or death due to lower respiratory tract infection) in individuals aged 60 years or older in LTCIs. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias. Effects on dichotomous outcomes were measured as risk differences (RDs) with 95% confidence intervals (CIs). We assessed the quality of evidence with GRADE. MAIN RESULTS: We identified four cluster-RCTs and one cohort study (n = 12,742) of influenza vaccination for HCWs caring for individuals >= 60 years in LTCIs. Four cluster RCTs (5896 residents) provided outcome data that addressed the objectives of our review. The studies were comparable in their study populations, intervention and outcome measures. The studies did not report adverse events. The principal sources of bias in the studies related to attrition, lack of blinding, contamination in the control groups and low rates of vaccination coverage in the intervention arms, leading us to downgrade the quality of evidence for all outcomes due to serious risk of bias.Offering influenza vaccination to HCWs based in long term care homes may have little or no effect on the number of residents who develop laboratory-proven influenza compared with those living in care homes where no vaccination is offered (RD 0 (95% CI -0.03 to 0.03), two studies with samples taken from 752 participants; low quality evidence). HCW vaccination probably leads to a reduction in lower respiratory tract infection in residents from 6% to 4% (RD -0.02 (95% CI -0.04 to 0.01), one study of 3400 people; moderate quality evidence). HCW vaccination programmes may have little or no effect on the number of residents admitted to hospital for respiratory illness (RD 0 (95% CI -0.02 to 0.02, one study of 1059 people; low quality evidence). We decided not to combine data on deaths from lower respiratory tract infection (two studies of 4459 people) or all cause deaths (four studies of 8468 people). The direction and size of difference in risk varied between the studies. We are uncertain as to the effect of vaccination on these outcomes due to the very low quality of evidence. Adjusted analyses, which took into account the cluster design, did not differ substantively from the pooled analysis with unadjusted data. AUTHORS' CONCLUSIONS: Our review findings have not identified conclusive evidence of benefit of HCW vaccination programmes on specific outcomes of laboratory-proven influenza, its complications (lower respiratory tract infection, hospitalisation or death due to lower respiratory tract illness), or all cause mortality in people over the age of 60 who live in care institutions. This review did not find information on co-interventions with healthcare worker vaccination: hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding admissions, antivirals and asking healthcare workers with influenza or influenza-like illness (ILI) not to work. This review does not provide reasonable evidence to support the vaccination of healthcare workers to prevent influenza in those aged 60 years or older resident in LTCIs. High quality RCTs are required to avoid the risks of bias in methodology and conduct identified by this review and to test further these interventions in combination. PMID- 27251462 TI - OGG1 is essential in oxidative stress induced DNA demethylation. AB - DNA demethylation is an essential cellular activity to regulate gene expression; however, the mechanism that triggers DNA demethylation remains unknown. Furthermore, DNA demethylation was recently demonstrated to be induced by oxidative stress without a clear molecular mechanism. In this manuscript, we demonstrated that 8-oxoguanine DNA glycosylase-1 (OGG1) is the essential protein involved in oxidative stress-induced DNA demethylation. Oxidative stress induced the formation of 8-oxoguanine (8-oxoG). We found that OGG1, the 8-oxoG binding protein, promotes DNA demethylation by interacting and recruiting TET1 to the 8 oxoG lesion. Downregulation of OGG1 makes cells resistant to oxidative stress induced DNA demethylation, while over-expression of OGG1 renders cells susceptible to DNA demethylation by oxidative stress. These data not only illustrate the importance of base excision repair (BER) in DNA demethylation but also reveal how the DNA demethylation signal is transferred to downstream DNA demethylation enzymes. PMID- 27251463 TI - Prevalence among adolescents in Bergen, Western Norway, of temporomandibular disorders according to the DC/TMD criteria and examination protocol. AB - OBJECTIVE: The aims of this study were to assess the prevalence of temporomandibular disorders (TMD) among adolescents and to contrast the prevalence of TMD according to the DC/TMD clinical examination protocol versus the prevalence of pain related to TMD according to two screening questions. MATERIAL AND METHODS: Two hundred and ten adolescents living in the county of Bergen, Norway, were offered an additional examination for TMD in connection with their regular dental check-up appointment. Five dental clinics were selected with differing socio-economic patient populations, as reflected by stratification of average levels of DMFT, and an equal number of girls and boys were invited to participate. The participants answered two screening questions for pain related to TMD followed by a clinical examination according to the DC/TMD protocol by five calibrated examiners. RESULTS: Acceptable calibration results were obtained. Approximately 80% of eligible participants consented to partake. According to the criteria of DC/TMD, the prevalence of TMD among the study participants was 11.9%, with a peak at 16 years of age. According to the self-reported screening questions for pain related to TMD, 7.2% responded positively. Only seven participants with a TMD diagnosis established according to the DC/TMD clinical examination protocol reported also pain related to TMD based on answering the two screening questions. CONCLUSION: The prevalence of TMD is higher for girls than for boys and the prevalence of TMD established according to the DC/TMD criteria was higher than the prevalence of pain related to TMD estimated by use of two screening questions for self-reported pain. PMID- 27251465 TI - Cooperative catalysis by bovine serum albumin-iodine towards cascade oxidative coupling-C(sp(2))-H sulfenylation of indoles/hydroxyaryls with thiophenols on water. AB - Cooperative cascade catalysis by bovine serum albumin (BSA)-iodine allows for the first time the performance of C(sp(2))-H sulfenylation of indole from readily available thiophenol (-SH bond) via in situ generation/cleavage of disulfide (S-S bond) in air under aqueous conditions, whereas BSA or I2 individually do not permit this two step sequence to occur in the same pot towards C-S bond formation. This green cooperative protocol is extendable to sulfenylation of hydroxyaryls (i.e. 2-naphthol or 4-hydroxycoumarin) with diverse thiols (aryl/heteroaryl) without using any toxic metal catalysts, bases or oxidants, thus rendering the process environmentally and economically reliable. Further, the gram scale synthesis of a COX-2 inhibitor (3-(pyridin-2-ylthio)-1H-indole), regioselectivity and recyclability (up to four cycles) are the additional merits of this cooperative cascade bio-chemocatalytic (BSA-I2) protocol. Moreover, HPLC and ESI-MS provide powerful insights into the mechanistic aspects of the above cascade sulfenylation reaction. PMID- 27251464 TI - Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress. AB - Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID- 27251466 TI - In vitro toxicity determination of antifungal constituents from Combretum zeyheri. AB - BACKGROUND: Candida albicans is one of the organisms living on the human body symbiotically, but, in hosts with low immunity it becomes one of the most pathogenic fungal organisms. Combretum zeyheri has been reported to have antifungal, antibacterial and antioxidant activities. Medicinal plants are believed to be non-toxic by the general public. Toxicity studies, however, have indicated that they are capable of causing numerous side effects, therefore, evaluation of safety is required. The objective of this study was to determine the toxicity of the antifungal constituents of Combretum zeyheri on mammalian cells. METHODS: Alkaloids, saponins, flavonoids-enriched extracts and crude ethanol extracts were prepared from the leaves of Combretum zeyheri. The broth microdilution method was used to investigate for antifungal activity, with miconazole used as the positive control. The MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide) assay was used to determine cell viability of the Candida albicans cells. The most potent extracts; the ethanol extract, alkaloids and saponins respectively, were further tested for their toxicity on sheep erythrocytes, mouse peritoneal macrophages and Jurkat T cells. RESULTS: All Combretum zeyheri extracts displayed a dose-dependent antifungal activity and had IC50 values ranging from 16 MUg/ml to 159 MUg/ml for Candida albicans. The alkaloids, saponins and ethanol extracts were found to be non-toxic towards mouse peritoneal cells and Jurkat T cells. In the haemolysis assay, all extracts were haemolytic at varying degrees and showed their greatest haemolytic activity at the highest concentration of 5 mg/ml. The saponins were the least haemolytic, followed by the ethanol extracts and the alkaloids respectively. Although these extracts were haemolytic to some extent, they may considered safe at therapeutic concentrations since there was a large difference between the antifungal IC50 and haemolysis EC50 values, hence a large therapeutic window. CONCLUSIONS: Combretum zeyheri antifungal constituents are, therefore, a potential source of lead compounds which can be developed into antifungal drugs of natural origin owing to Combretum zeyheri's effective antifungal activity and low toxicity to mammalian cells. PMID- 27251467 TI - The Interactive Use of Multi-Dimensional Modeling and 3D Printing in Preplanning of Type A Aortic Dissection. AB - We report a technique of multidimensional modeling and 3D printing in preplanning of Type A acute aortic dissection (TAAD) repair. doi: 10.1111/jocs.12772 (J Card Surg 2016;31:441-445). PMID- 27251468 TI - Effortful semantic decision-making boosts memory performance in older adults. AB - A major concern in age-related cognitive decline is episodic memory (EM). Previous studies indicate that both resource and binding deficits contribute to EM decline. Environmental support by task manipulations encouraging stronger cognitive effort and deeper levels of processing may facilitate compensation for these two deficits. To clarify factors that can counteract age-related EM decline, we assessed effects of cognitive effort (four levels) and level of processing (LoP, shallow/deep) during encoding on subsequent retrieval. Young (YAs, N = 23) and older (OAs, N = 23) adults performed two incidental encoding tasks, deep/semantic and shallow/perceptual. Cognitive effort was manipulated by varying decision-making demands. EM performance, indexed by d-prime, was later tested using a recognition task. Results showed that regardless of LoP, increased cognitive effort caused higher d-primes in both age groups. Compared to YAs, OAs showed a lower d-prime after shallow encoding across all cognitive effort levels, and after deep encoding with low cognitive effort. Deep encoding with higher levels of cognitive effort completely eliminated these age differences. Our findings support an environmental-compensatory account of cognitive ageing and can have important therapeutic implications. PMID- 27251469 TI - Heterogeneous characteristics of MRI changes of thigh muscles in patients with dysferlinopathy. AB - INTRODUCTION: The aim of this study was to evaluate the pattern of thigh muscle MRI changes in a large cohort of patients with dysferlinopathy. METHODS: MRI of the thigh was performed in 60 patients. We correlated the scale of muscle involvement on MRI with the modified Gardner-Medwin and Walton (GM-W) scale and disease duration. We also analyzed the relationship between muscle changes and genetic mutations. RESULTS: Fatty infiltration and edema were observed in 95.50% and 86.67% of patients, respectively. The hamstring muscles had the highest frequency and mean score of fatty infiltration, although a posterior-dominant pattern was found in only 56%. Edema most commonly and severely affected the quadriceps and adductor magnus muscles. Fatty infiltration score correlated positively with disease duration and GM-W scale. CONCLUSIONS: The pattern of fatty infiltration was heterogeneous in dysferlinopathy patients. Muscle edema was common. Fatty infiltration can be used to assess disease progression. Muscle Nerve 54: 1072-1079, 2016. PMID- 27251470 TI - Image-based quantification of 3D morphology for bifurcations in the left coronary artery: Application to stent design. AB - BACKGROUND: Improved strategies for stent-based treatment of coronary artery disease at bifurcations require a greater understanding of artery morphology. OBJECTIVE: We developed a workflow to quantify morphology in the left main coronary (LMCA), left anterior descending (LAD), and left circumflex (LCX) artery bifurcations. METHODS: Computational models of each bifurcation were created for 55 patients using computed tomography images in 3D segmentation software. Metrics including cross-sectional area, length, eccentricity, taper, curvature, planarity, branching law parameters, and bifurcation angles were assessed using open-sources software and custom applications. Geometric characterization was performed by comparison of means, correlation, and linear discriminant analysis (LDA). RESULTS: Differences between metrics suggest dedicated or multistent approaches should be tailored for each bifurcation. For example, the side branch of the LCX (i.e., obtuse marginal; OM) was longer than that of the LMCA (i.e., LCXprox) and LAD (i.e., first diagonal; D1). Bifurcation metrics for some locations (e.g., LMCA Finet ratio) provide results and confidence intervals agreeing with prior findings, while revised metric values are presented for others (e.g., LAD and LCX). LDA revealed several metrics that differentiate between artery locations (e.g., LMCA vs. D1, LMCA vs. OM, LADprox vs. D1, and LCXprox vs. D1). CONCLUSIONS: These results provide a foundation for elucidating common parameters from healthy coronary arteries and could be leveraged in the future for treating diseased arteries. Collectively the current results may ultimately be used for design iterations that improve outcomes following implantation of future dedicated bifurcation stents. (c) 2015 Wiley Periodicals, Inc. PMID- 27251472 TI - Dissecting the role of transforming growth factor-beta1 in topmouth culter immunobiological activity: a fundamental functional analysis. AB - Transforming growth factor-beta1 (TGF-beta1) has been proven to function primarily in mammalian immunobiological activity, but information regarding the immune role of TGF-beta1 in teleosts is limited. In the present study, we describe the cDNA cloning and characterization of the TGF-beta1 molecule in the topmouth culter. TGF-beta1 is highly expressed in immune-related tissues of the culter, including the thymus, head kidney, and spleen. The recombinant culter TGF beta1 (cTGF-beta1) was successfully expressed and purified in vitro, and the effects of cTGF-beta1 on the mRNA expression of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta, in the absence or presence of LPS was determined in culter peripheral blood leukocytes. cTGF-beta1 was found to have bipolar properties in inflammatory reactions. Additionally, to assess the immune role of teleost TGF-beta1 in vivo, the expression of TGF-beta1 in the culter thymus and spleen tissues induced by poly I:C were also examined. The expression of TGF beta1 was obviously up-regulated, as shown in the cell lines. However, the peak time of cTGF-beta1 expression in the cell lines occurred significantly earlier than in the organic tissues under the same inducer, suggesting that the response of the teleost TGF-beta1 molecule to exogenous infection depends on a more complicated signalling pathway in vivo than in vitro. PMID- 27251474 TI - Vaginal cuff dehiscence: a randomized trial comparing robotic vaginal cuff closure methods. AB - The purpose of this study is to compare the rate of vaginal cuff dehiscence between two different methods of closure in patients undergoing robotic-assisted total laparoscopic hysterectomy and explore variables related to postoperative breakdown. This was a prospective, randomized controlled study with two arms. The control group (Arm 1) underwent single-layer continuous closure while the study group (Arm 2) had three additional imbricating figure-of-X sutures placed in addition to the standard protocol. Of the 263 patients who completed the study, 4 patients (1.49 %) experienced dehiscence of the vaginal cuff. Three of the four patients with dehiscence received the standard single vaginal cuff closure (Arm 1) and the one remaining case of dehiscence underwent the protocol with additional sutures (Arm 2). All patients who experienced dehiscence were current smokers. Our study suggests that there may be benefit in adding additional sutures to the standard single-layer vaginal cuff closure procedure. Physicians should evaluate smoking status before deciding on a vaginal cuff closure method. PMID- 27251475 TI - Non-coordinating anions assemble cyanine amphiphiles into ultra-small fluorescent nanoparticles. AB - A non-coordinating anion, fluorinated tetraphenylborate, assembles specially designed cationic cyanine amphiphiles into 7-8 nm fluorescent nanoparticles that are >40-fold brighter than a single cyanine dye. This kind of anion, combining hydrophobic and electrostatic forces in aqueous media, constitutes promising building blocks in the self-assembly of functional nanomaterials. PMID- 27251471 TI - Functional Impact of Ryanodine Receptor Oxidation on Intracellular Calcium Regulation in the Heart. AB - Type 2 ryanodine receptor (RyR2) serves as the major intracellular Ca2+ release channel that drives heart contraction. RyR2 is activated by cytosolic Ca2+ via the process of Ca2+-induced Ca2+ release (CICR). To ensure stability of Ca2+ dynamics, the self-reinforcing CICR must be tightly controlled. Defects in this control cause sarcoplasmic reticulum (SR) Ca2+ mishandling, which manifests in a variety of cardiac pathologies that include myocardial infarction and heart failure. These pathologies are also associated with oxidative stress. Given that RyR2 contains a large number of cysteine residues, it is no surprise that RyR2 plays a key role in the cellular response to oxidative stress. RyR's many cysteine residues pose an experimental limitation in defining a specific target or mechanism of action for oxidative stress. As a result, the current understanding of redox-mediated RyR2 dysfunction remains incomplete. Several oxidative modifications, including S-glutathionylation and S-nitrosylation, have been suggested playing an important role in the regulation of RyR2 activity. Moreover, oxidative stress can increase RyR2 activity by forming disulfide bonds between two neighboring subunits (intersubunit cross-linking). Since intersubunit interactions within the RyR2 homotetramer complex dictate the channel gating, such posttranslational modification of RyR2 would have a significant impact on RyR2 function and Ca2+ regulation. This review summarizes recent findings on oxidative modifications of RyR2 and discusses contributions of these RyR2 modifications to SR Ca2+ mishandling during cardiac pathologies. PMID- 27251473 TI - Current status of various neurovascular bundle-sparing techniques in robot assisted radical prostatectomy. AB - Nerve-sparing procedures during robot-assisted radical prostatectomy (RARP) have demonstrated improved postoperative functional outcomes. This article provides an overview of clinically applied prostatic neuro-anatomy, various techniques of nerve sparing (NS), and recent innovations in NS and potency outcomes of NS RARP. We retrieved and reviewed all listed publications within PubMed using keywords: nerve sparing, robotic radical prostatectomy, prostate cancer, outcomes, pelvic neuroanatomy and potency. Studies reporting potency outcomes of NS RARP (comparative and non-comparative) were analysed using the Delphi method with an expert panel of urological robotic surgeons. Herein, we outline the published techniques of NS during RARP. Potency and continence outcomes of individual series are discussed in light of the evidence provided by case series and published trials. The potency outcomes of various comparative and non-comparative series of NS RARP have also been mentioned. There are numerous NS techniques reported for RARP. Each method is complimented with benefits and constrained by idiosyncratic caveats, and thus, careful patient selection, a wise intraoperative clinical judgment and tailored approach for each patient is required, when decision for nerve sparing is made. Further large prospective multi-institutional randomized controlled trials are required to evaluate potency and continence outcomes of these techniques, using a rigid standard patient selection criteria and definition of potency are warranted in the new era of functional outcome driven research. PMID- 27251477 TI - Mediterranean Diet and cancer risk: an open issue. AB - The traditional Mediterranean Diet of the early 1960s meets the characteristics of an anticancer diet defined by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AIRC). A diet rich of whole grains, pulses, vegetables and fruits, limited in high-calorie foods (foods high in sugar or fat), red meat and foods high in salt, without sugary drinks and processed meat is recommended by the WCRF/AIRC experts to reduce the risk of cancer. The aim of this review was to examine whether Mediterranean Diet is protective or not against cancer risk. Three meta-analyses of cohort studies reported that a high adherence to the Mediterranean Diet significantly reduces the risk of cancer incidence and/or mortality. Nevertheless, the Mediterranean dietary pattern defined in the studies' part of the meta-analyses has qualitative and/or quantitative differences compared to the Mediterranean Diet of the early 1960s. Therefore, the protective role of the Mediterranean Diet against cancer has not definitely been established. In epidemiological studies, a universal definition of the Mediterranean Diet, possibly the traditional Mediterranean Diet of the early 1960s, could be useful to understand the role of this dietary pattern in cancer prevention. PMID- 27251476 TI - Relationship between genotype and arcuate fasciculus morphology in six young children with global developmental delay: Preliminary DTI stuy. AB - PURPOSE: To investigate whether different genetic mutations observed in children with global developmental delay (GD) are associated with unique patterns of the arcuate fasciculus dysmorphology. MATERIALS AND METHODS: Six children with GD (age: 36.8 +/- 14.1 months, 5 boys) having mutations in MID1, CDK4, SFRP1, EN2, RXRG-GLRB, or MECP2, and five children with typical development (TD, age: 38.5 +/ 20.5 months, 4 boys) underwent a 3 Tesla MRI including diffusion weighted imaging (DWI). Five language pathway segments in the left hemisphere, "C1 : Broca's to Wernicke's area," "C2 : Broca's to premotor area," "C3 : premotor to Wernicke's area," "C4 : Wernicke's to inferior parietal area," and "C5 : premotor to inferior parietal area" were objectively identified using the DWI "maximum a posteriori probability" classifier. RESULTS: Affinity propagation clustering analysis found that three arcuate pathway segments, C1,2,4 , of MID1, CDK4, EN2, and MECP2 had a similar pattern of volume ratio while those of SFRP1 and RXRG GLRB had a heterogeneous pattern of volume ratio (net similarity = -0.01). Using receiver operating characteristic curve analysis, the fiber ratios of C1,2,4 showed a high probability to discriminate between GD and TD, yielding an accuracy of 0.91, 0.91, 1.00, respectively. The fiber volumes of C1 and C4 showed a strong correlation with expressive language (R2 = 0.6019; P-value = 0.033) and receptive language (R2 = 0.6379; P-value = 0.028), respectively. CONCLUSION: The findings of the present study provide preliminary evidence to suggest that different segments of the arcuate fasciculus are formed under the regulation of different genes which, when mutated, may result in developmental delay. J. Magn. Reson. Imaging 2016;44:1504-1512. PMID- 27251478 TI - [Management of intraoperative carcinoid crises]. PMID- 27251479 TI - [Does the time interval between diagnosis and treatment influence survival of patients with resectable esophageal cancer?]. PMID- 27251480 TI - [Mediastinitis]. PMID- 27251481 TI - [RCT of chemoembolization plus rediofrequency ablation versus liver resection for hepatocellular carcinoma]. PMID- 27251482 TI - [Surgery without anatomy?]. AB - Anatomy is the basis of all operative medicine. While this branch of scientific medicine is frequently not explicitly mentioned in surgical publications, it is nonetheless quintessential to medical education. In the era of video sequences and digitized images, surgical methods are frequently communicated in the form of cinematic documentation of surgical procedures; however, this occurs without the help of explanatory drawings or subtexts that would illustrate the underlying anatomical nomenclature, comment on fine functionally important details or even without making any mention of the surgeon. In scientific manuscripts color illustrations frequently appear in such overwhelming quantities that they resemble long arrays of trophies but fail to give detailed explanations that would aid the therapeutic translation of the novel datasets. In a similar fashion, many anatomy textbooks prefer to place emphasis on illustrations and photographs while supplying only a paucity of explanations that would foster the understanding of functional contexts and thus confuse students and practitioners alike. There is great temptation to repeat existing data and facts over and over again, while it is proportionally rare to make reference to truly original scientific discoveries. A number of examples are given in this article to illustrate how discoveries that were made even a long time ago can still contribute to scientific progress in current times. This includes the NO signaling molecules, which were first described in 1775 but were only discovered to have a pivotal role as neurotransmitters in the function of human paradoxical sphincter muscles in 2012 and 2015. Readers of scientific manuscripts often long for explanations by the numerous silent coauthors of a publication who could contribute to the main topic by adding in-depth illustrations (e. g. malignograms, evolution and involution of lymph node structures). PMID- 27251483 TI - [Sternal osteomyelitis - Surgical treatment concepts]. AB - Sternal osteomyelitis is a potentially fatal condition following cardiac surgery. Sternal osteomyelitis should be diagnosed as early as possible followed by an interdisciplinary radical debridement. Subsequently plastic reconstructive surgery is necessary for defect reconstruction. This can be achieved by a number of established pedicled and free flap plastic surgery procedures. The choice of flap procedures is based on defect geometry and the individual patient situation, including potential flap donor sites. Smaller defects can generally be reconstructed by pedicled flap transfer. For extensive sternal defects, free flap transplantation is now a well-established therapeutic option. In some patients lacking sufficient recipient vessels, the creation of an arteriovenous (AV) loop as recipient vessel is necessary. In summary, successful therapy of sternal osteomyelitis is based on early interdisciplinary treatment by the various surgical subspecialties. PMID- 27251484 TI - Syndromes that Mimic an Excess of Mineralocorticoids. AB - Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of renin and aldosterone. It can be due to endogenous or exogenous substances that mimic the effector mechanisms of aldosterone, leading not only to alterations of electrolytes and hypertension, but also to an increased inflammatory reaction in several tissues. Enzymatic defects of adrenal steroidogenesis (deficiency of 17alpha-hydroxylase and 11beta hydroxylase), mutations of mineralocorticoid receptor (MR) and alterations of expression or saturation of 11-hydroxysteroid dehydrogenase type 2 (apparent mineralocorticoid excess syndrome, Cushing's syndrome, excessive intake of licorice, grapefruits or carbenoxolone) are the main causes of pseudohyperaldosteronism. In these cases treatment with dexamethasone and/or MR blockers is useful not only to normalize blood pressure and electrolytes, but also to prevent the deleterious effects of prolonged over-activation of MR in epithelial and non-epithelial tissues. Genetic alterations of the sodium channel (Liddle's syndrome) or of the sodium-chloride co-transporter (Gordon's syndrome) cause abnormal sodium and water reabsorption in the distal renal tubules and hypertension. Treatment with amiloride and thiazide diuretics can respectively reverse the clinical picture and the renin aldosterone system. Finally, many other more common situations can lead to an acquired pseudohyperaldosteronism, like the expansion of volume due to exaggerated water and/or sodium intake, and the use of drugs, as contraceptives, corticosteroids, beta-adrenergic agonists and FANS. In conclusion, syndromes or situations that mimic aldosterone excess are not rare and an accurate personal and pharmacological history is mandatory for a correct diagnosis and avoiding unnecessary tests and mistreatments. PMID- 27251485 TI - Children's use of evaluative devices in spoken and written narratives. AB - This study investigated the development of evaluation in narratives from middle to late childhood, within the context of differentiating between spoken and written modalities. Two parallel forms of a picture story were used to elicit spoken and written narratives from fourth- and sixth-graders. It was expected that, in addition to an increase of evaluative devices with age, written narratives would exhibit a higher frequency and diversity as a result of the intrinsic differences between the two modalities. From a developmental perspective, the results showed that only few categories exhibited the expected increase with age. Qualitative analyses provided a fruitful method to illustrate developmental changes. The results further indicated that modality had the expected impact on the diversity, and on the frequency, of most categories of evaluative language. Specifically, markers of decontextualized language and categories with a high degree of syntactic complexity were prone to modality differences. PMID- 27251486 TI - The Genetics of Success: How Single-Nucleotide Polymorphisms Associated With Educational Attainment Relate to Life-Course Development. AB - A previous genome-wide association study (GWAS) of more than 100,000 individuals identified molecular-genetic predictors of educational attainment. We undertook in-depth life-course investigation of the polygenic score derived from this GWAS using the four-decade Dunedin Study (N = 918). There were five main findings. First, polygenic scores predicted adult economic outcomes even after accounting for educational attainments. Second, genes and environments were correlated: Children with higher polygenic scores were born into better-off homes. Third, children's polygenic scores predicted their adult outcomes even when analyses accounted for their social-class origins; social-mobility analysis showed that children with higher polygenic scores were more upwardly mobile than children with lower scores. Fourth, polygenic scores predicted behavior across the life course, from early acquisition of speech and reading skills through geographic mobility and mate choice and on to financial planning for retirement. Fifth, polygenic-score associations were mediated by psychological characteristics, including intelligence, self-control, and interpersonal skill. Effect sizes were small. Factors connecting DNA sequence with life outcomes may provide targets for interventions to promote population-wide positive development. PMID- 27251488 TI - Dentate Circuitry as a Model to Study Epileptogenesis. AB - Epileptogenesis, which can be initiated by brain insults or gene mutations in the normal brain, is defined as the gradual (months to years) process of epilepsy development that begins before the first epileptic seizure. Epileptogenic changes include induction of immediate early genes, post-translational modification of ion-channel functions, neuronal death, gliosis, and reorganization of neural circuits. Each of these changes alone or in combination can contribute to an epileptogenic focus, which is defined by the minimal cortical region that is necessary and sufficient to induce synchronized epileptic bursting activity in neurons. Therefore to discover and develop anti-epileptogenic drugs it is essential to unveil the cellular and molecular mechanisms underlying the development of epileptogenic foci. Among the epileptogenic changes, abnormally appended excitatory recurrent circuits can directly cause synchronized bursting of neuron activity. Here, I will introduce and discuss the mechanisms underlying the development of two representative abnormal neural circuits, namely, hippocampal mossy fiber sprouting and ectopic granule cells, which are found in the dentate gyrus of patients with mesial temporal lobe epilepsy and its animal models. PMID- 27251487 TI - Extralaryngeal branching of the recurrent laryngeal nerve: a meta-analysis of 28,387 nerves. AB - INTRODUCTION: The recurrent laryngeal nerves (RLN) are branches of the vagus nerve that go on to innervate most of the intrinsic muscles of the larynx. Historically, the RLN has been considered to branch after it enters the larynx, but numerous studies have demonstrated that it often branches before. The wide variability of this extralaryngeal branching (ELB) has significant implications for the risk of iatrogenic injury. We aimed to assess the anatomical characteristics of ELB comprehensively. METHODS: Articles on the ELB of the RLN were identified by a comprehensive database search. Relevant data were extracted and pooled into a meta-analysis of the prevalence of branching, branching pattern, distance of ELB point from the larynx, and presence of positive motor signals in anterior and posterior ELB branches. RESULTS: A total of 69 articles (n = 28,387 nerves) from both intraoperative and cadaveric modalities were included in the meta-analysis. The overall pooled prevalence of ELB was 60.0 % (95 % CI 52.0-67.7). Cadaveric and intraoperative subgroups differed with prevalence rates of 73.3 % (95 % CI 61.0-84.0) and 39.2 % (95 % CI 29.0-49.9), respectively. Cadavers most often presented with a ELB pattern of bifurcation, with a prevalence of 61.1 %, followed by no branching at 23.4 %. Branching of the RLN occurred most often at a distance of 1-2 cm (74.8 % of cases) prior to entering the larynx. A positive motor signal was most often noted in anterior RLN branches (99.9 %) but only in 1.5 % of posterior branches. CONCLUSIONS: The anatomy of the RLN is highly variable, and ELB is likely to have been underreported in intraoperative studies. Because of its high likelihood, the possibility of ELB needs to be assessed in patients to prevent iatrogenic injury and long-term postoperative complications. PMID- 27251489 TI - Foreword. PMID- 27251490 TI - A Standardized Method for the Preparation of a Gas Phase Extract of Cigarette Smoke. AB - The gas phase of cigarette smoke is important from the viewpoint of human health, because it can pass through alveolar epithelium and enter the circulation. There is no standard method for the preparation of a gas phase extract of cigarette smoke (CSE), although CSE is widely used for research instead of whole cigarette smoke. We have established a standard method for the preparation of CSE. One cigarette per trial is continuously combusted under a reduced pressure generated by an aspiration pump with a velocity of 1.050 L/min: the main stream of the smoke is passed through a Cambridge filter to remove tar, and subsequently, bubbled through a glass ball filter (pore size, 20-30 um) into 15 mL of phosphate buffered saline (PBS). To express the concentration of CSE, a virtual tar concentration is introduced, which is calculated assuming that tar trapped on the Cambridge filter is dissolved in the PBS. CSEs prepared from smaller numbers of cigarettes (original virtual tar concentration<=15 mg/mL) show similar concentration-response curves for cytotoxicity versus virtual tar concentrations. CSEs prepared from various brands of cigarettes and by different smoking regimes (continuous and puff smoking) show similar cytotoxic potency if the virtual tar concentrations are the same. In conclusion, using the standardized method for CSE preparation in combination with the virtual tar concentration, it becomes possible to simply and rapidly prepare standard CSEs with defined concentrations from any brand of cigarettes, which are toxicologically equivalent to CSE prepared by puff smoking. PMID- 27251491 TI - Mass Spectrometric Approaches to the Identification of Potential Ingredients in Cigarette Smoke Causing Cytotoxicity. AB - Cigarette smoke contains many harmful chemicals that contribute to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease, cancer, and cardiovascular disease. Many studies have been done to identify cytotoxic chemicals in cigarette smoke and elucidate the onset of the above-mentioned diseases caused by smoking. However, definitive mechanisms for cigarette smoke toxicity remain unknown. As candidates for cytotoxic chemicals, we have recently found methyl vinyl ketone (MVK) and acetic anhydride in nicotine/tar-free cigarette smoke extract (CSE) using L-tyrosine (Tyr), an amino acid with highly reactive hydroxyl group. The presence of MVK and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS). We also found new reaction products formed in B16-BL6 mouse melanoma (B16-BL6) cells treated with CSE using LC/MS. These were identified as glutathione (GSH) conjugates of alpha,beta-unsaturated carbonyl compounds, MVK, crotonaldehyde (CA), and acrolein (ACR), by the mass value and product ion spectra of these new products. ACR and MVK are type-2 alkenes, which are well known as electron acceptors and form Michael-type adducts to nucleophilic side chain of amino acids on peptides. These alpha,beta-unsaturated carbonyl compounds may have a key role in CSE-induced cell death. PMID- 27251492 TI - Carbonyl Compounds in the Gas Phase of Cigarette Mainstream Smoke and Their Pharmacological Properties. AB - Cigarette mainstream smoke is composed of gas and tar phases and contains >4000 chemical constituents, including nicotine and tar. The substances in the gas phase but not in the tar phase can pass through the airway epithelial barrier, enter the systemic circulation via the pulmonary circulation, and increase systemic oxidative damage, leading to the development of cigarette smoking related diseases such as atherosclerosis. Recently, we identified some stable carbonyl compounds, including acrolein (ACR) and methyl vinyl ketone (MVK), as major cytotoxic factors in nicotine- and tar-free cigarette smoke extract (CSE) of the gas phase. CSE, ACR, and MVK induce protein kinase C (PKC)-dependent activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and subsequent generation of reactive oxygen species (ROS) via NOX, causing plasma membrane damage and cell apoptosis. CSE, ACR, and MVK also trigger carbonylation of PKC, which is an irreversible oxidative modification. Cell damage and PKC carbonylation in response to treatment with CSE, ACR, or MVK are abolished by thiol-containing antioxidants such as N-acetyl-L-cysteine and reduced glutathione. Thus pharmacological modulation of PKC and NOX activities and the trapping of ROS are potential strategies for the prevention of diseases related to cigarette smoking. PMID- 27251493 TI - Recent Progress in Analytical Methods for Determination of Urinary 3 Hydroxypropylmercapturic Acid, a Major Metabolite of Acrolein. AB - 3-Hydroxypropylmercapturic acid (3-HPMA), a major metabolite of acrolein in urine, has been recognized as a noninvasive biomarker of exposure to cigarette smoke. Since acrolein is formed endogenously from polyamines and is also formed during oxidative stress and aggravates tissue damage by changing protein activity through its conjugation in pathological lesions, it is thought that the urinary 3 HPMA level is useful as a biomarker to monitor the severity of several diseases related to acrolein. To study the correlation between 3-HPMA and disease severity, it is important to understand the properties of analytical methods for determination of 3-HPMA. In this article, we summarize the analytical methods for determination of urinary 3-HPMA and discuss the utility of 3-HPMA as one of the biomarkers for the diagnosis of brain infarction. PMID- 27251494 TI - Antigenotoxic and Antioxidant Properties of Solanum cernuum and Its Alkaloid, Cernumidine. AB - Solanum cernuum VE. has been used extensively for the treatment of urinary disorders, gonorrhea and skin infections; cernumidine is a major component of S. cernuum (SC) hydroalcoholic extract. The micronucleus test in V79 cells was used to evaluate the genotoxic and antigenotoxic potential of SC and cernumidine. For antigenotoxicity assessment, methyl methanesulfonate (MMS, 44 ug/mL) and hydrogen peroxide (H2O2, 3.5 ug/mL) were added as inducers of chromosome damage. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. Significantly higher frequencies of micronuclei were observed in cell cultures treated with SC concentrations of 160 and 320 ug/mL in comparison with the negative control, demonstrating a genotoxic effect. There was no significant difference in the frequency of micronuclei between cell cultures treated with a combination of SC and MMS and those treated only with MMS. On the other hand, a significant reduction in the frequency of micronuclei was observed for V79 cells treated with SC or cernumidine plus H2O2 compared to those treated only with H2O2. Furthermore, SC and cernumidine were able to scavenge free radicals in the DPPH assay. Thus, the protective effect of SC and cernumidine against H2O2 can be attributed to antioxidant activity. PMID- 27251495 TI - Effects of All trans-Retinoic Acid on Alveolar Regeneration in Dexamethasone Induced Emphysema Models and Its Relationship to Exposure in ICR and FVB Mice. AB - During the past two decades, it has been reported that treatment with all-trans retinoic acid (ATRA) induces alveolar regeneration in rodent emphysema models. In the present study, we investigated the regeneration by ATRA at various exposure conditions in two strains of mice with induced emphysema. The emphysema model was created by postnatal administration of dexamethasone to ICR and FVB mice, which were then treated with ATRA from postnatal day 42. The regeneration was observed in ICR mice but not in FVB mice given 10 and 40 mg/kg/d ATRA for 10 d. The concentration-time profiles of ATRA in plasma and lung were similar in both strains. These results suggest that the strain difference in the regeneration by ATRA was not caused by differences in the exposure to ATRA. On the other hand, the regeneration in ICR mice was enhanced by an increase of the intraperitoneal dose in the range of 10-40 mg/kg/d for 10 d. At an intraperitoneal dose of 40 mg/kg/d, the regeneration was observed after 10 and 20 d of treatment but not after 1 to 5 d of treatment. Meanwhile, the regeneration by intraperitoneal administration of ATRA was enhanced more than that by oral administration. Exposure to ATRA during repeated intraperitoneal administration to ICR mice was higher than that in oral administration. The results suggest that the regeneration in ICR mice requires at least 10 d of treatment with ATRA and its effects depend on the exposure to ATRA in plasma, which parallels that in lung. PMID- 27251496 TI - Effect of 1.8-Cineole in Dermatophagoides pteronyssinus-Stimulated Bronchial Epithelial Cells and Mouse Model of Asthma. AB - 1.8-Cineole (eucalyptol) is a phytoncide, a volatile organic compound derived from plants. Phytoncides are known to have an anti-inflammatory effect. However, the effects of 1.8-cineole in house dust mite (HDM)-stimulated bronchial epithelial cells are poorly understood. The objective of this study was to assess the effect of 1.8-cineole in HDM-stimulated bronchial epithelial cells and in the HDM-induced murine asthma model. The purpose of the present study is to evaluate the anti-inflammatory effects and mechanism of 1.8-cineole action in HDM-induced airway inflammation. Human bronchial epithelial cells (HBECs) were cultured with Dermatophagoides pteronyssinus (Der p) and 1.8-cineole. Cytokine protein levels, phosphorylation of protein kinases, and intracellular Toll-like receptor 4 (TLR4) expressions were measured. In the murine model, BALB/C mice were sensitized with Der p and were exposed to Der p via intranasal route during the challenge period. 1.8-Cineole was given by inhalation 6 h before the each challenge. Treatment with 1.8-cineole inhibited the Der p-induced cytokine protein expression, phosphorylation of p38 mitogen-activated protein kinase (MAPK) and Akt and intracellular TLR4 expression in HBECs. In the Der p-induced mouse model, airway hyper-responsiveness (AHR) and the number of eosinophils in bronchoalveolar lavage fluid (BALF) was also significantly reduced by 1.8-cineole treatment. The treatment of 1.8-cineole inhibited the increased production of interleukin (IL) 4, IL-13 and IL-17A in BALF after Der p challenge. These results suggest that 1.8 cineole suppresses Der p-induced IL-8, IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) production in HBECs. Finally, we confirmed that 1.8 cineole decreases AHR and eosinophilic airway inflammation in Der p-induced asthma mice. PMID- 27251497 TI - Effect of pH on the Misincorporation Rate of DNA Polymerase eta. AB - The many known eukaryotic DNA polymerases are classified into four families; A, B, X, and Y. Among them, DNA polymerase eta, a Y family polymerase, is a low fidelity enzyme that contributes to translesional synthesis and somatic hypermutation. Although a high mutation frequency is observed in immunoglobulin genes, translesional synthesis occurs with a high accuracy. We determined whether the misincorporation rate of DNA polymerase eta varies with ambient conditions. It has been reported that DNA polymerase eta is unable to exclude water molecules from the active site. This finding suggests that some ions affect hydrogen bond formation at the active site. We focused on the effect of pH and evaluated the misincorporation rate of deoxyguanosine triphosphate (dGTP) opposite template T by DNA polymerase eta at various pH levels with a synthetic template-primer. The misincorporation rate of dGTP by DNA polymerase eta drastically increased at pH 8.0-9.0 compared with that at pH 6.5-7.5. Kinetic analysis revealed that the Km value for dGTP on the misincorporation opposite template T was markedly affected by pH. However, this drastic change was not seen with the low fidelity DNA polymerase alpha. PMID- 27251498 TI - Simultaneous Addition of Shikonin and Its Derivatives with Lipopolysaccharide Induces Rapid Macrophage Death. AB - Macrophages play pivotal roles in inflammatory responses. Previous studies showed that various natural products exert antiinflammatory effects by regulating macrophage activation. Recent studies have shown that shikonin (SHK) and its derivatives (beta-hydroxyisovalerylshikonin, acetylshikonin, and isobutylshikonin), which are 1,4-naphthoquinone pigments extracted from the roots of Lithospermum erythrorhizon, have various pharmacological, including antiinflammatory and antitumor, effects. Even though there have been many studies on the antiinflammatory activities of SHK derivatives, only a few have described their direct effects on macrophages. We investigated the effects of SHK derivatives on lipopolysaccharide (LPS)-treated macrophages. Low doses of SHK derivatives induced significant macrophage cytotoxicity (mouse macrophage-like J774.1/JA-4 cells and mouse peritoneal macrophages) in the presence of LPS. SHK activated caspases-3 and -7, which led to DNA fragmentation, but this cytotoxicity was prevented through a pan-caspase inhibitor in LPS-treated JA-4 cells. Maximal cytotoxic effects were achieved when SHK was added immediately before LPS addition. These results indicate that SHK derivatives induce caspase dependent apoptotic cell death of LPS-treated macrophages and suggest that SHK acts during an early stage of LPS signaling. PMID- 27251499 TI - Preparation of Angiopep-2 Peptide-Modified Bubble Liposomes for Delivery to the Brain. AB - In the development of therapeutic approaches for central nervous system diseases, a significant obstacle is efficient drug delivery across the blood-brain barrier owing to its low permeability. Various nanocarriers have been developed for brain targeted drug delivery by modification with specific ligands. We have previously developed polyethylene glycol-modified liposomes (Bubble liposomes [BLs]) that entrap ultrasound (US) contrast gas and can serve as both plasmid DNA or small interfering RNA carriers and US contrast agents. In this study, we attempted to prepare brain-targeting BLs modified with Angiopep-2 (Ang2) peptide (Ang2-BLs). Ang2 is expected to be a useful ligand for the efficient delivery of nanocarriers to the brain. We showed that Ang2-BLs interacted specifically with brain endothelial cells via low-density lipoprotein receptor-related protein-1. We also confirmed that Ang2-BLs could entrap US contrast gas and had US imaging ability as well as unmodified BLs. Furthermore, we demonstrated that Ang2-BLs accumulated in brain tissue after intravascular injection. These results suggested that Ang2 BLs may be a useful tool for brain-targeted delivery and US imaging via systemic administration. PMID- 27251500 TI - Effects of Constituent Compounds of Smilax china on Nicotine-Induced Endothelial Dysfunction in Human Umbilical Vein Endothelial Cells. AB - This study investigated the effects of compounds isolated from 70% ethanol (EtOH) extraction of Smilax china L. (SCE), a plant belonging to the family Smilacaceae on nicotine-induced endothelial dysfunction (ED) in human umbilical vein endothelial cells. We isolated 10 compounds from ethyl acetate (EtOAc) fraction of 70% EtOH extract of SCE and investigated their inhibitory effect on nicotine induced ED in endothelial cells. Kaempferol, kaempferol 7-O-alpha-L rhamnopyranoside, puerarin and ferulic acid showed strong inhibition of nicotine induced vascular cell adhesion molecule (VCAM-1) expression while kaempferol, kaempferin, and caffeic acid attenuated intercellular adhesion molecule (ICAM-1) expression. Lepidoside, caffeic acid and methylsuccinic acid caused the highest up-regulated expression of endothelial nitric oxide synthase at the protein level with caffeic acid and ferulic acid showing strong inhibitory effects on inducible nitric oxide synthase (iNOS) expression. In addition, ferulic acid and kaempferol showed inhibition against interleukin-8 (IL-8) and interleukin-1beta (IL-1beta) expression while ferulic acid and caffeic acid showed comparatively higher inhibition of ED associated tumor necrosis factor-alpha (TNF-alpha) expression. These results show the potential of the aforementioned compounds to reverse the toxic effects of nicotine on the endothelium. PMID- 27251501 TI - Indirubin 3'-Epoxide Induces Caspase-Independent Cell Death in Human Neuroblastoma. AB - Indirubin inhibits cyclin-dependent kinases by binding to their ATP-binding site, thereby exerting potent cytotoxicity on some tumor cells. We examined the anti tumor effect of indirubin 3'-epoxide on human neuroblastoma cell lines (IMR-32, SK-N-SH, and NB-39). The results revealed potent cytotoxicity of indirubin 3' epoxide against the IMR-32 (IC50: 0.16 uM) and SK-N-SH (IC50: 0.07 uM) cells. Furthermore, it also induced an increase of the sub-G1 population in the IMR-32 cells. Examination by Hoechst 33342 staining revealed apoptosis characterized by cell shrinkage, nuclear condensation and nuclear fragmentation in a concentration dependent manner. Furthermore, annexin V-propidium iodide (PI) double-staining revealed an increase in the percentage of early apoptotic cells following treatment of the cells with indirubin 3'-epoxide without activation of caspases. In addition, significant decreases in the protein level of survivin and poly(ADP ribose)polymerase (PARP), and increase in that of apoptosis-inducing factor (AIF) were found in the nuclei of the cells. These results suggest that indirubin 3' epoxide induced caspase-independent apoptosis through mechanisms involving DNA fragmentation and inhibition of DNA repair. PMID- 27251502 TI - Effect of a Ferric Citrate Formulation, a Phosphate Binder, on Oxidative Stress in Chronic Kidney Diseases-Mineral and Bone Disorder Patients Receiving Hemodialysis: A Pilot Study. AB - A ferric citrate formulation for treating hyperphosphatemia is a new therapeutic that not only suppresses the accumulation of phosphorus in patients with chronic kidney disease-mineral bone disorders (CKD-MBD), but also ameliorates anemia caused by iron deficiency. In contrast, it has been demonstrated that intravenous iron injection markedly increases oxidative stress. This study was designed to investigate the effect of a ferric citrate formulation on oxidative stress in CKD MBD patients receiving hemodialysis therapy. Fifteen CKD-MBD patients undergoing dialysis were enrolled in this study. The patients were orally administered a ferric citrate formulation for 6 months. Their plasma phosphorus concentrations remained unchanged with the switch from other phosphorus adsorbents to the ferric citrate formulation. In addition, the ferric citrate formulation generally allowed for dose reduction of an erythropoiesis stimulating agent with an increased hematopoietic effect. The average values of plasma ferritin level increased after the introduction of a ferric citrate formulation, but did not exceed 100 (ng/mL). Interestingly, oxidative stress markers did not increase significantly, and anti-oxidative capacity was not significantly decreased at 6 months after the drug administration. Similarly, no change was observed in any inflammation markers. The ferric citrate formulation induces negligible oxidative stress in CKD-MBD patients receiving dialysis under the present clinical condition. PMID- 27251503 TI - Prevention of Barrier Disruption by Heme Oxygenase-1 in Intestinal Bleeding Model. AB - In this study we investigated the effect of free heme, the local level of which was increased by bleeding, on the intestinal barrier function, using human epithelial colorectal adenocarcinoma cells (Caco-2). Our results show that the addition of hemin to the culture medium markedly disrupted the barrier function, which was significantly improved by glutamine supplementation. Although hemin treatment caused the increased expression of heme oxygenase (HO)-1, the inhibition of HO activity resulted in the aggravation of hemin-induced barrier dysfunction. Up-regulation of HO-1 by pretreatment with a low concentration of hemin almost completely prevented hemin-induced barrier dysfunction. Taken together, these observations indicate that an abnormally high level of intracellular free heme causes barrier dysfunction, probably through the modulation of proteins forming tight junctions. PMID- 27251504 TI - Modeling and Simulation for Estimating the Influence of Renal Dysfunction on the Hypouricemic Effect of Febuxostat in Hyperuricemic Patients Due to Overproduction or Underexcretion of Uric Acid. AB - Whether renal dysfunction influences the hypouricemic effect of febuxostat, a xanthine oxidase (XO) inhibitor, in patients with hyperuricemia due to overproduction or underexcretion of uric acid (UA) remains unclear. We aimed to address this question with a modeling and simulation approach. The pharmacokinetics (PK) of febuxostat were analyzed using data from the literature. A kinetic model of UA was retrieved from a previous human study. Renal UA clearance was estimated as a function of creatinine clearance (CLcr) but non renal UA clearance was assumed constant. A reversible inhibition model for bovine XO was adopted. Integrating these kinetic formulas, we developed a PK pharmacodynamic (PK-PD) model for estimating the time course of the hypouricemic effect of febuxostat as a function of baseline UA level, febuxostat dose, treatment duration, body weight, and CLcr. Using the Monte Carlo simulation method, we examined the performance of the model by comparing predicted UA levels with those reported in the literature. We also modified the models for application to hyperuricemia due to UA overproduction or underexcretion. Thirty nine data sets comprising 735 volunteers or patients were retrieved from the literature. A good correlation was observed between the hypouricemic effects of febuxostat estimated by our PK-PD model and those reported in the articles (observed) (r=0.89, p<0.001). The hypouricemic effect was estimated to be augmented in patients with renal dysfunction irrespective of the etiology of hyperuricemia. While validation in clinical studies is needed, the modeling and simulation approach may be useful for individualizing febuxostat doses in patients with various clinical characteristics. PMID- 27251505 TI - Protective Effects of Ethyl Acetate Soluble Fraction of Limonium tetragonum on Diethylnitrosamine-Induced Liver Fibrosis in Rats. AB - Diethylnitrosamine (DEN) is a potent toxic material that can cause necrosis and subsequent fibrosis in the liver. Based on the previously reported hepatoprotective effect of Limonium tetragonum against the proliferation of hepatic stellate cells, we tested the EtOAc soluble fraction of L. tetragonum extract (EALT) in a DEN-induced hepatotoxic rat model. The development of hepatotoxicity including mononuclear cell infiltration and fibrosis induced by intraperitoneal injections of DEN (70 mg/2 mL/kg body weight (b.w.) per week) was observed at 4, 6 and 8 weeks after the first DEN treatment. Administration of EALT (200 mg/kg body weight, per os (p.o.)) induced significant reductions in serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and triglycerides (TG) in DEN-injected rats. Increased oxidative stress in DEN-induced liver fibrosis rats was diminished by EALT treatment through a decrease in malondialdehyde (MDA) and increase in superoxide dismutase (SOD). Histologic findings that included markedly attenuated mononuclear cell infiltration and fibrosis could be observed in liver samples from the EALT-treated groups. An extract of Hovenia dulcis fruit and Sylimarin were used as positive controls. The present study provides direct experimental evidence for EALT attenuated hepatic injury and fibrosis in DEN treated mice. The L. tetragonum EtOAc fraction might be useful in treating fibrotic liver diseases. PMID- 27251506 TI - Methyl-beta-Cyclodextrin Impairs the Monocyte-Adhering Ability of Endothelial Cells by Down-Regulating Adhesion Molecules and Caveolae and Reorganizing the Actin Cytoskeleton. AB - Due to its powerful ability to deplete cholesterol from the plasma membrane of cells, methyl-beta-cyclodextrin (MbetaCD) has been widely used as a putative research tool in cell biology. Recently, recruiting MbetaCD as an effective drug (e.g., antitumor drugs) has been developed. However, it remains unclear whether MbetaCD, when it enters the blood circulation as a drug, influences the functions of the endothelium, e.g., the adhesion of leukocytes to the endothelium. In this study, we found that MbetaCD can impair the adhesion of monocytes to the monolayer of endothelial cells by lowering the cell-surface adhesive force and expression of adhesion molecules and caveolae-related molecules on/in endothelial cells, and reorganizing the actin cytoskeleton of endothelial cells. The data imply that MbetaCD, when recruited as a drug, potentially helps to inhibit inflammation or initiation/progression of atherosclerosis since its important early step is the adhesion of circulating leukocytes (e.g., monocytes) to the endothelium. PMID- 27251507 TI - Glucosamines Attenuate Bone Loss Due to Menopause by Regulating Osteoclast Function in Ovariectomized Mice. AB - The effect of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) on bone metabolism in ovariectomized (OVX) mice was studied. After 12 weeks of feeding with 0.2% GlcN and 0.2% GlcNAc, the femoral bone mineral density in OVX mice was significantly increased compared with that in OVX mice fed the control diet. Histomorphometric analysis of the tibia indicated that the rates of osteogenesis and bone resorption were reduced due to the GlcN diet. The erosion depth of osteoclasts on the tibia in GlcN- and GlcNAc-fed OVX mice was significantly lower than that in the control OVX mice. The number of tartrate-resistant acid phosphatase-positive osteoclasts induced from bone marrow stem cells isolated from GlcN-fed OVX mice was significantly lower than that from control OVX mice. A loss of uterine weight and higher serum calcium concentration in the GlcN- and GlcNAc-fed OVX mice were observed. The results suggest that the intake of GlcN suppresses bone loss by inhibiting osteoclast differentiation and activity in a nonestrogenic manner. PMID- 27251508 TI - Carbon Tetrachloride-Induced Nephrotoxicity in Mice Is Prevented by Pretreatment with Zinc Sulfate. AB - Carbon tetrachloride (CCl4) is commonly used as a chemical inducer of experimental liver injury. In addition, many studies showed that CCl4 can induce kidney damage. In the current study, we evaluated the protective effect of zinc (Zn) against CCl4-induced nephrotoxicity. We hypothesized that this protective effect would result from the ability of Zn to serve as an inducer of metallothionein (MT), a known endogenous scavenger of free radicals. We administered Zn (as ZnSO4) 50 mg/kg subcutaneously once daily for 3 successive days prior to a single intraperitoneal administration of CCl4 4 g/kg in male ddY mice. Our results showed that Zn pretreatment significantly decreased creatinine and blood urea nitrogen levels and reduced renal histopathological damage at 6 h post-CCl4 injection, observations consistent with enhanced antioxidative activity in the kidney. Moreover, kidney MT levels in the Zn+CCl4-treated group decreased by greater than 70% compared with levels in the Zn-alone group, implying that MT was consumed by CCl4-induced radicals. These findings suggest that prophylaxis with Zn protects mice from CCl4-induced acute nephrotoxicity, presumably by induction of MT, which in turn scavenges radicals induced by CCl4 exposure. PMID- 27251509 TI - Potentiation of Methylmercury-Induced Death in Rat Cerebellar Granular Neurons Occurs by Further Decrease of Total Intracellular GSH with BDNF via TrkB in Vitro. AB - Brain-derived neurotrophic factor (BDNF) is a principal factor for neurogenesis, neurodevelopment and neural survival through a BDNF receptor, tropomyosin-related kinase (Trk) B, while BDNF can also cause a decrease in the intracellular glutathione (GSH) level. We investigated the exacerbation of methylmercury induced death of rat cerebellar granular neurons (CGNs) by BDNF in vitro. Since methylmercury can decrease intracellular GSH levels, we hypothesized that a further decrease of the intracellular GSH level is involved in the process of the exacerbation of neuronal cell death. In the present study, we established that in CGN culture, a decrease of the intracellular GSH level was further potentiated with BDNF in the process of the methylmercury-induced neuronal death and also in GSH reducer-induced neuronal death. BDNF treatment promoted the decrease in GSH levels induced by methylmercury and also by L-buthionine sulfoximine (BSO) and diethyl maleate (DEM). The promoting effect of BDNF was observed in a TrkB-vector transformant of the rat neuroblastoma B35 cell line but not in the mock-vector transformant. These results indicate that the exacerbating effect of BDNF on methylmercury-induced neuronal death in cultures of CGNs includes a further decrease of intracellular GSH levels, for which TrkB is essential. PMID- 27251510 TI - Protective Effect of Dimethyl Fumarate on an Oxidative Stress Model Induced by Sodium Nitroprusside in Mice. AB - Recent reports have shown that dimethyl fumarate (DMF) prevents brain damage induced by intracerebral hemorrhage and this beneficial effect is mediated by the nuclear erythroid 2 p45-related factor-2-antioxidant response element (Nrf2-ARE) pathway. However, the downstream mechanism underlying the activation of the Nrf2 ARE pathway is unclear. Here, we investigated the protective effect of DMF using an in vivo model of oxidative stress induced by sodium nitroprusside (SNP) and rat primary striatal cultures. Oral administration of DMF prevented SNP-induced motor dysfunction. Pre-administration of DMF (60-200 mg/kg) for 24 h dose dependently protected against brain damage induced by the striatal injection of SNP. Next, we investigated the protective effect and mechanism of DMF against oxidative stress using rat primary striatal cell cultures. Treatment of striatal cells with DMF (10 uM) markedly prevented hydrogen peroxide-induced cytotoxicity. The protective effect of DMF against oxidative stress in vitro was inhibited by zinc protoporphyrin IX, an inhibitor of heme oxygenase-1, but not by buthionine sulfoximine, an inhibitor of glutathione synthesis. These results suggest that the activation of heme oxygenase-1 plays an important role in the protective effect of DMF. PMID- 27251511 TI - Regulation of Human Kv1.4 Channel Activity by the Antidepressant Metergoline. AB - Metergoline is an ergot-derived psychoactive drug that is a ligand for various serotonin and dopamine receptors. Little is known about the effect of metergoline on different types of receptors and ion channels. Potassium channels are the most diverse group of ion channels. Kv1.4, a shaker family K channel alpha subunit, is one of a family of voltage gated K channels that mediates transient and rapid inactivating A-type currents and N-type inactivation. We demonstrated previously that metergoline inhibited the activity of neuronal voltage-dependent Na(+) channels in Xenopus laevis oocytes (Acta Pharmacol. Sin., 35, 2014, Lee et al.). In this study, we sought to elucidate the regulatory effects underlying metergoline-induced human Kv1.4 channel inhibition. We used the two electrode voltage-clamp (TEVC) technique to investigate the effect of metergoline on human Kv1.4 channel currents in Xenopus laevis oocytes expressing human Kv1.4 alpha subunits. Interestingly, metergoline treatment also induced inhibition of peak currents in human Kv1.4 channels in a concentration-dependent manner. The IC50 of peak currents of hKv1.4 currents was 3.6+/-0.6 uM. These results indicate that metergoline might regulate the human Kv1.4 channel activity that is expressed in X. laevis oocytes. Further, this regulation of potassium currents by metergoline might be one of the pharmacological actions of metergoline-mediated psychoactivity. PMID- 27251512 TI - Vaccination with Antigen Combined with alphabeta-ATP as a Vaccine Adjuvant Enhances Antigen-Specific Antibody Production via Dendritic Cell Activation. AB - Adjuvants are required to enhance antigen-specific immune responses by vaccines. Extracellular ATP serves as a danger signal to alert the immune system of tissue damage by acting on P2X and P2Y receptors and triggers the activation of dendritic cells (DCs). Here we investigated the in vivo adjuvant efficacy of alpha,beta-methylene-ATP (alphabeta-ATP), a non-hydrolysable form of ATP. We found that intradermal injection of ovalbumin (OVA), as a model antigen, combined with alphabeta-ATP, as the adjuvant, enhanced OVA-specific immune responses more than OVA alone. Additionally, DCs in the skin of mice injected with OVA and alphabeta-ATP had increased expression of major histocompatibility complex class II and co-stimulator molecules, CD40, CD80, and CD86, suggesting that alphabeta ATP activated DC. These findings indicate that alphabeta-ATP functions as a potent vaccine adjuvant. PMID- 27251513 TI - Locomotor-Reducing Activity of Sesquiterpenes Related to Zingiber zerumbet Essential Oil and Hexahydrozerumbone Derivatives. AB - Zerumbone derivatives 1-4 are 11-membered cyclic compounds synthesised from a sesquiterpene zerumbone obtained from the rhizomes of Zingiber zerumbet SMITH (Zingiberaceae). In this study, we investigated the locomotor-reducing effects of hexahydrozerumbone derivatives 1-3 and zerumbol 4, and those of beta caryophyllene 5 and caryophyllene oxide 6, which are present in Z. zerumbet essential oil. The absence of the double bond at C6 weakened the locomotor reducing effects. beta-Caryophyllene 5 and caryophyllene oxide 6 showed locomotor reducing effects in mice at 4.5*10(-3) mg/cage. Moreover, locomotor activity increased significantly at 0.45 mg/cage of caryophyllene oxide 6. PMID- 27251514 TI - Drug preparation, injection, and sharing practices in Tajikistan: a qualitative study in Kulob and Khorog. AB - BACKGROUND: Sharing injection equipment remains an important rout of transmission of HIV and HCV infections in the region of Eastern Europe and Central Asia. Tajikistan is one of the most affected countries with high rates of injection drug use and related epidemics.The aim of this qualitative study was to describe drug use practices and related behaviors in two Tajik cities - Kulob and Khorog. METHODS: Twelve focus group discussions (6 per city) with 100 people who inject drugs recruited through needle and syringe program (NSP) outreach in May 2014. Topics covered included specific drugs injected, drug prices and purity, access to sterile equipment, safe injection practices and types of syringes and needles used. Qualitative thematic analysis was performed using NVivo 10 software. RESULTS: All participants were male and ranged in age from 20 to 78 years. Thematic analysis showed that cheap Afghan heroin, often adulterated by dealers with other admixtures, was the only drug injected. Drug injectors often added Dimedrol (Diphenhydramine) to increase the potency of "low quality" heroin. NSPs were a major source of sterile equipment. Very few participants report direct sharing of needles and syringes. Conversely, many participants reported preparing drugs jointly and sharing injection paraphernalia. Using drugs in an outdoor setting and experiencing withdrawal were major contributors to sharing equipment, using non-sterile water, not boiling and not filtering the drug solution. CONCLUSION: Qualitative research can provide insights into risk behaviors that may be missed in quantitative studies. These finding have important implications for planning risk reduction interventions in Tajikistan. Prevention should specifically focus on indirect sharing practices. PMID- 27251515 TI - Surgical treatment options for septic arthritis of the hip in children. AB - Septic arthritis is the result of bacterial infection of the hip joint and is often found in infants and toddlers. It is the most common septic joint condition during growth and may cause the most devastating complications without prompt and proper treatment. Early diagnosis and intervention are required to avoid irreversible complications. This review documents the systematic approach to diagnosis and management of septic arthritis in children. PMID- 27251516 TI - Labial adhesion in children at the Jos University Teaching Hospital. AB - BACKGROUND: Labial adhesion is one of the most common reasons for gynaecologic consultations in children. We sought to determine the prevalence of labial adhesions, mode of presentation and treatment in children at the Jos University Teaching Hospital. MATERIALS AND METHODS: A retrospective study of labial adhesions in children from January 2004 to December 2013. Data on paediatric gynaecological consultations, and labial adhesions were retrieved from the gynaecological clinic and the theatre records. The case notes of those with labial adhesions were retrieved and the relevant data extracted. RESULTS: The total number of paediatric patients seen at the gynaecology clinic over the study period was 379 and 25 had labial adhesion (6.6%). The majority (88%) presented in the first 2 years of life, all the patients were asymptomatic, and 2 (8%) had surgical separation of the adhesions while the rest were managed conservatively. A total of 5 (20%) came for follow-up. While 2 (8%) came a week later following surgical management, 3 (12%) came back more than 6 months later due to recurrence following conservative management. CONCLUSION: Labial adhesions account for significant proportion of paediatric gynaecologic consultations. They are usually asymptomatic, occur in the first 2 years of life and frequently managed conservatively. PMID- 27251517 TI - Topical tranexamic acid as a novel treatment for bleeding peptic ulcer: A randomised controlled trial. AB - BACKGROUND: Peptic ulcers are among the most common causes of upper gastrointestinal (GI) bleeding in children. The standard care for GI bleeding is endoscopy for diagnostic and therapeutic purposes. We aimed to assess the effect of topical tranexamic acid (TXA) via endoscopic procedures in children with GI bleeding caused by bleeding ulcers. PROCEDURE: In this randomised controlled trial, 120 children were evaluated by diagnostic procedures for GI bleeding, of which 63 (30 girls, 33 boys) aged 1-month to 15 years were recruited. The patients were randomly divided into case and control groups. In the case group, TXA was administered directly under endoscopic therapy. In the control group, epinephrine (1/10,000) was submucosally injected to the four quadrants of ulcer margins as the routine endoscopic therapy. In both groups, the patients received supportive medical therapy with intravenous fluids and proton pump inhibitor drugs. RESULTS: The mean +/- standard deviation age of the children was 5 +/- 2.03 years. Rebleeding occurred in 15 (11.4%) and 21 (9.8%) patients in the case and control groups, respectively (P = 0.50). The frequency of blood transfusion episodes (P = 0.06) and duration of hospital stay (P = 0.07) were not statistically different between the groups. CONCLUSION: Using topical TXA via endoscopic procedures may be effective in cases of GI bleedings caused by active bleeding ulcers. In order to establish this therapeutic effect, a large number of clinical studies are needed. PMID- 27251518 TI - Correlation between adenoidal nasopharyngeal ratio and symptoms of enlarged adenoids in children with adenoidal hypertrophy. AB - BACKGROUND: Adenoid hypertrophy is one of the most common health problems affecting the paediatric population. This study aims to correlate adenoidal nasopharyngeal ratio (ANR) with symptoms of enlarged adenoids in children with enlarged adenoids. MATERIALS AND METHODS: It was a year, cross-sectional, hospital-based study conducted at Lautech Teaching Hospital, Osogbo. ANR was determined by dividing adenoidal depth with nasopharyngeal depth on the plain lateral radiographs. RESULTS: A total of 90 consecutive children consisting of 61 males and 29 females were included in the study with M:F ratio of 2.1:1. Their ages ranged from 8 months to 11 years. All the patients presented with nasal obstruction, mouth breathing and noisy breathing. Majority (64.5%) had severe obstructions with preponderance among children of 3-5 years (39.9%). Linear regression analysis showed significant association between age and ANR (t = 10.447, P < 0.001). There was high significant association (P < 0.05) between presenting symptoms and degree of nasopharyngeal airway obstruction; for snoring (r = 0.251, P = 0.000), sleep apnoea (r = 0.594, P = 0.000), nasal discharge (r = 0.314, P = 0.001), excessive daytime sleepiness (r = 0.219, P = 0.019) and failure to thrive (r = 0.240, P = 0.011). CONCLUSION: Lateral X-ray of the nasopharynx is an effective tool to evaluate children with suspected adenoid hypertrophy. It correlates well with patients' symptoms and provides objective measures of adenoid hypertrophy. PMID- 27251519 TI - One-stage vs. three-stage repair in anorectal malformation with rectovestibular fistula. AB - BACKGROUND: Anorectal malformations (ARMs) disease is one of the congenital anomalies with an incidence of about 1 in 5000 neonate births, and treatment requires surgical intervention. Selecting the one- or three-step surgical procedure to treat the disease, especially in female neonates with rectovestibular fistula, is a subject of debate. This study aims to compare the advantages and disadvantages of these two methods. MATERIALS AND METHODS: Forty female neonates with ARM and rectovestibular fistula between March 2011 and March 2013 were included in the study, and they were divided into two equal groups. Allocation of the first case was random, and all cases were then allocated alternatively (every other subject was assigned to a treatment group) until each group received 20 cases equally patients of study group underwent a one-stage posterior sagittal anorectoplasty (PSARP) and in control group patients underwent a three-stage operation (colostomy, PSARP, and closure of colostomy). The complications during and after the surgery were recorded in both groups, and the results were compared. RESULTS: In the control group, only one case (5%) of wound infection and dehiscence was seen, whereas in the one-stage study group, six cases (30%) of wound infection and dehiscence were seen (P value = 0.046). However, regarding the incidence of other complications, such as iatrogenic vaginal injury as well as final recovery, no considerable differences were seen between the two groups. CONCLUSIONS: Despite more surgical site infections and dehiscence in the one-stage repair, but due to the numerous advantages compared to the three-stage method, which is more time-consuming, more costly, and causes more adverse effect on parents and children, performing the one-stage repair is recommended for this anomaly. PMID- 27251520 TI - Comparison of trans-perineal ultrasound-guided pressure augmented saline colostomy distension study and conventional contrast radiographic colostography in children with anorectal malformation. AB - BACKGROUND: In children with high and intermediate anorectal malformation, distal colostography is an important investigation done to determine the relationship between the position of the rectal pouch and the probable site of the neo-anus as well as the presence or absence of a fistula. Conventionally, this is done using contrast with fluoroscopy or still X-ray imaging. This, however, has the challenges of irradiation, availability and affordability, especially in developing countries. This study compared the accuracy of trans-perineal ultrasound-guided pressure augmented saline colostomy distension study (SCDS) with conventional contrast distal colostography (CCDC) in the determination of the precise location of the distal rectal pouch and in detecting the presence and site of fistulous communication between the rectum and the urogenital tract was studied. MATERIALS AND METHODS: Trans-perineal ultrasound-guided pressure augmented SCDS, CCDC and intra-operative measurements were done sequentially for qualified infants with anorectal malformation and colostomy. Pouch skin distance and presence or absence of recto urinary or genital fistula was measured prospectively in each case. Statistical significance was inferred at P-value of <0.01. RESULTS: There were thirteen infants, 9 males and 4 females. The age at onset of investigation ranged from 2 to 12 months with a median value of 9 months. Using paired t-test at a confidence interval of 95%, the P value when SCDS values are compared with CCDC is 0.19; and 0.06 when SCDS was compared with intra-operative measurements. Hence, there is no statistical difference as P > 0.01. On its ability to detect presence or absence of a fistula: SCDS had a sensitivity of 50.0%, specificity of 100.0%, accuracy of 69.2%, negative predictive value of fistulas of 55.6% and a positive predictive value of fistulas of 100.0%. CONCLUSION: Ultrasound-guided pressure augmented SCDS can safely and reliably be used to assess the distal colonic anatomy and the presence of fistula in infants with Anorectal malformation who are on colostomy. PMID- 27251521 TI - Forgotten/retained double J ureteric stents: A source of severe morbidity in children. AB - BACKGROUND: The increase in the usage of double J (DJ) ureteral stents in the management of a variety of urinary tract disease processes mandates familiarity with these devices, their consequences and their potential complications, which at times can be devastating. We retrospectively reviewed our series of children with forgotten/retained DJ ureteric stents. MATERIALS AND METHODS: Hospital records of all patients' <18 years old who underwent removal of forgotten/retained DJ ureteral stent at our hospital were reviewed for age, gender, indication for insertion of DJ stent, duration of stent insertion, radiological images and surgical procedures performed. RESULTS: During the study period, January 2000 to December 2014 (a 15-year period), a total of 14 children underwent removal of forgotten/retained DJ ureteral stent. A combination of extracorporeal shock wave lithotripsy, cystolitholapaxy and percutaneous nephrolithotomy was done to free the DJ stent and extract it. CONCLUSIONS: Forgotten/retained stents in children are a source of severe morbidity, additional/unnecessary hospitalisation and definitely financial strain. PMID- 27251522 TI - Umbilical only access laparoscopic pyeloplasty in children: Preliminary report. AB - BACKGROUND: Over the past three decades, laparoscopic surgery has become a well established alternative to open surgery in the management of ureteropelvic junction (UPJ) obstruction. Currently, several efforts are being made, aimed at further reducing the morbidity associated with conventional laparoscopy. We report our experience with modified umbilical port laparoscopic pyeloplasty in children. MATERIALS AND METHODS: Children presenting with hydronephrosis secondary to UPJ obstruction formed the study group. A 5 mm endoscopic port was placed on the inferior umbilical crease. The two 3 mm instruments were introduced through puncture sites created a few mm superior and lateral to the endoscopic port, under vision. Total operating time, the time taken for insertion of double pigtail catheter, time taken for pyeloplasty anastomosis and complications were noted. RESULTS: During the study period, 16 children underwent modified umbilical only access laparoscopic pyeloplasty. The total operating time and the time for insertion of double pigtail catheter were significantly more in our earlier half of cases. CONCLUSIONS: Modified umbilical port laparoscopic pyeloplasty reduces the morbidity associated with conventional multiport laparoscopy without the need of expensive multichannel cannulas, curved laparoscopic instruments and longer laparoscopic endoscopes. Though crossing instruments are a factor which prolongs the duration of surgery, it does not hinder complex suturing needed during pyeloplasty. PMID- 27251523 TI - Endoscopic removal of impacted oesophageal foreign body: A case report and a review of literature. AB - Foreign body (FB) impaction in the oesophagus is fairly common in paediatric Gastroenterology practice. This study aims to describe a case of an unusually impacted button lithium battery, in the mid-oesophagus of a 7-year-old child that was confirmed, and removed during oesophagogastroduodenoscopy. A 7-year-old male child, presented at the Emergency Paediatric Unit of our hospital with a history of ingestion of a button-like metallic object. A plain soft tissue X-ray of the neck and chest, however, revealed a dense round object located at the sternal angle of Louis. The object was dislodged and identified as a flat lithium battery after an oesophagogastroduodenoscopy, carried out under general anaesthesia using a flexible forward-viewing video gastroscope. The button battery was subsequently passed in faeces. Endoscopic removal of impacted oesophageal FBs under general anaesthesia is an effective and safe procedure in children in experienced hands. PMID- 27251524 TI - Early diagnosis of post-varicella necrotising fasciitis: A medical and surgical emergency. AB - Necrotising fasciitis (NF) is an extremely rare complication of a rather common paediatric viral exanthem varicella. Delayed diagnosis and treatment can lead to significant morbidity and mortality. Laboratory risk indicator of NF score aids in early clinical diagnosis in suspected cases of post-varicella NF thus enabling timely intervention. Surgery delayed for more than 24 hours, is an independent risk factor for death. Surgical debridement with good antibiotic coverage is the definitive treatment for NF. PMID- 27251525 TI - Congenital diaphragmatic hernia, Meckel's diverticulum and malrotation in a 3 month-old infant. AB - Congenital diaphragmatic hernia (CDH) is a common developmental anomaly that usually presents in the neonatal period. It is known to be associated with cardiac, renal, genital and chromosomal anomalies. Late presentation of CDH (beyond 1-month of age) is seen in 13% of the cases. Malrotation is reported in 42% of CDH cases. We report a case of a 3-month-old infant with concurrent CDH, Meckel's diverticulum and malrotation. This is the first case report of such an association in an infant. PMID- 27251526 TI - Oesophageal pseudodiverticulum after foregut duplication cyst excision: Case report and literature review. AB - Oesophageal pseudodiverticula rarely occur after excision of benign oesophageal neoplasms. While management and outcomes have been reported in the adult leiomyoma literature, sparse data exist on the occurrence and management of pseudodiverticula after foregut duplication cyst excision. We discuss our experience with a paediatric patient and review relevant literature regarding operative techniques and surgical outcomes. PMID- 27251527 TI - Congenital hernias and hydrocele: Importance of age. PMID- 27251528 TI - Pre-impact fall detection. AB - Pre-impact fall detection has been proposed to be an effective fall prevention strategy. In particular, it can help activate on-demand fall injury prevention systems (e.g. inflatable hip protectors) prior to fall impacts, and thus directly prevent the fall-related physical injuries. This paper gave a systematical review on pre-impact fall detection, and focused on the following aspects of the existing pre-impact fall detection research: fall detection apparatus, fall detection indicators, fall detection algorithms, and types of falls for fall detection evaluation. In addition, the performance of the existing pre-impact fall detection solutions were also reviewed and reported in terms of their sensitivity, specificity, and detection/lead time. This review also summarized the limitations in the existing pre-impact fall detection research, and proposed future research directions in this field. PMID- 27251529 TI - Universal stress protein HRU1 mediates ROS homeostasis under anoxia. AB - Plant survival is greatly impaired when oxygen levels are limiting, such as during flooding or when anatomical constraints limit oxygen diffusion. Oxygen sensing in Arabidopsis thaliana is mediated by Ethylene Responsive Factor (ERF) VII transcription factors, which control a core set of hypoxia- and anoxia responsive genes responsible for metabolic acclimation to low-oxygen conditions. Anoxic conditions also induce genes related to reactive oxygen species (ROS). Whether the oxygen-sensing machinery coordinates ROS production under anoxia has remained unclear. Here we show that a low-oxygen-responsive universal stress protein (USP), Hypoxia Responsive Universal Stress Protein 1 (HRU1), is induced by RAP2.12 (Related to Apetala 2.12), an ERF-VII protein, and modulates ROS production in Arabidopsis. We found that HRU1 is strongly induced by submergence, but that this induction is abolished in plants lacking RAP2.12. Mutation of HRU1 through transfer DNA (T-DNA) insertion alters hydrogen peroxide production, and reduces tolerance to submergence and anoxia. Yeast two-hybrid and bimolecular fluorescence complementation (BiFC) analyses reveal that HRU1 interacts with proteins that induce ROS production, the GTPase ROP2 and the NADPH oxidase RbohD, pointing to the existence of a low-oxygen-specific mechanism for the modulation of ROS levels. We propose that HRU1 coordinates oxygen sensing with ROS signalling under anoxic conditions. PMID- 27251530 TI - Regulation of resource exchange in the arbuscular mycorrhizal symbiosis. AB - Arbuscular mycorrhizal (AM) fungi are one of the most important groups of plant symbionts. These fungi provide mineral nutrients to plants in exchange for carbon. Although substantial amounts of resources are exchanged, the factors that regulate trade in the AM symbiosis are poorly understood. Recent evidence for the reciprocally regulated exchange of resources by AM fungi and plants has led to the suggestion that these symbioses operate according to biological market dynamics, in which interactions are viewed from an economic perspective, and the most beneficial partners are favoured. Here we present five arguments that challenge the importance of reciprocally regulated exchange, and thereby market dynamics, for resource exchange in the AM symbiosis, and suggest that such reciprocity is only found in a subset of symbionts, under specific conditions. We instead propose that resource exchange in the AM symbiosis is determined by competition for surplus resources, functional diversity and sink strength. PMID- 27251532 TI - Visualizing the dynamic structure of the plant photosynthetic membrane. AB - The chloroplast thylakoid membrane is the site for the initial steps of photosynthesis that convert solar energy into chemical energy, ultimately powering almost all life on earth. The heterogeneous distribution of protein complexes within the membrane gives rise to an intricate three-dimensional structure that is nonetheless extremely dynamic on a timescale of seconds to minutes. These dynamics form the basis for the regulation of photosynthesis, and therefore the adaptability of plants to different environments. High-resolution microscopy has in recent years begun to provide new insights into the structural dynamics underlying a number of regulatory processes such as membrane stacking, photosystem II repair, photoprotective energy dissipation, state transitions and alternative electron transfer. Here we provide an overview of the essentials of thylakoid membrane structure in plants, and consider how recent advances, using a range of microscopies, have substantially increased our knowledge of the thylakoid dynamic structure. We discuss both the successes and limitations of the currently available techniques and highlight newly emerging microscopic methods that promise to move the field beyond the current 'static' view of membrane organization based on frozen snapshots to a 'live' view of functional membranes imaged under native aqueous conditions at ambient temperature and responding dynamically to external stimuli. PMID- 27251531 TI - Woody biomass production lags stem-girth increase by over one month in coniferous forests. AB - Wood is the main terrestrial biotic reservoir for long-term carbon sequestration(1), and its formation in trees consumes around 15% of anthropogenic carbon dioxide emissions each year(2). However, the seasonal dynamics of woody biomass production cannot be quantified from eddy covariance or satellite observations. As such, our understanding of this key carbon cycle component, and its sensitivity to climate, remains limited. Here, we present high-resolution cellular based measurements of wood formation dynamics in three coniferous forest sites in northeastern France, performed over a period of 3 years. We show that stem woody biomass production lags behind stem-girth increase by over 1 month. We also analyse more general phenological observations of xylem tissue formation in Northern Hemisphere forests and find similar time lags in boreal, temperate, subalpine and Mediterranean forests. These time lags question the extension of the equivalence between stem size increase and woody biomass production to intra annual time scales(3, 4, 5, 6). They also suggest that these two growth processes exhibit differential sensitivities to local environmental conditions. Indeed, in the well-watered French sites the seasonal dynamics of stem-girth increase matched the photoperiod cycle, whereas those of woody biomass production closely followed the seasonal course of temperature. We suggest that forecasted changes in the annual cycle of climatic factors(7) may shift the phase timing of stem size increase and woody biomass production in the future. PMID- 27251533 TI - Arabidopsis D6PK is a lipid domain-dependent mediator of root epidermal planar polarity. AB - Development of diverse multicellular organisms relies on coordination of single cell polarities within the plane of the tissue layer (planar polarity). Cell polarity often involves plasma membrane heterogeneity generated by accumulation of specific lipids and proteins into membrane subdomains. Coordinated hair positioning along Arabidopsis root epidermal cells provides a planar polarity model in plants, but knowledge about the functions of proteo-lipid domains in planar polarity signalling remains limited. Here we show that Rho-of-plant (ROP) 2 and 6, phosphatidylinositol-4-phosphate 5-kinase 3 (PIP5K3), DYNAMIN-RELATED PROTEIN (DRP) 1A and DRP2B accumulate in a sterol-enriched, polar membrane domain during root hair initiation. DRP1A, DRP2B, PIP5K3 and sterols are required for planar polarity and the AGCVIII kinase D6 PROTEIN KINASE (D6PK) is a modulator of this process. D6PK undergoes phosphatidylinositol-4,5-bisphosphate- and sterol dependent basal-to-planar polarity switching into the polar, lipid-enriched domain just before hair formation, unravelling lipid-dependent D6PK localization during late planar polarity signalling. PMID- 27251534 TI - Decentralized circadian clocks process thermal and photoperiodic cues in specific tissues. AB - The circadian clock increases organisms' fitness by regulating physiological responses(1). In mammals, the circadian clock in the suprachiasmatic nucleus (SCN) governs daily behavioural rhythms(2). Similarly, in Arabidopsis, tissue specific circadian clock functions have emerged, and the importance of the vasculature clock for photoperiodic flowering has been demonstrated(3-5). However, it remains unclear if the vasculature clock regulates the majority of physiological responses, like the SCN in mammals, and if other environmental signals are also processed by the vasculature clock. Here, we studied the involvement of tissue-specific circadian clock regulation of flowering and cell elongation under different photoperiods and temperatures. We found that the circadian clock in vascular phloem companion cells is essential for photoperiodic flowering regulation; by contrast, the epidermis has a crucial impact on ambient temperature-dependent cell elongation. Thus, there are clear assignments of roles among circadian clocks in each tissue. Our results reveal that, unlike the more centralized circadian clock in mammals, the plant circadian clock is decentralized, where each tissue specifically processes individual environmental cues and regulates individual physiological responses. Our new conceptual framework will be a starting point for deciphering circadian clock functions in each tissue, which will lead to a better understanding of how circadian clock processing of environmental signals may be affected by ongoing climate change(6). PMID- 27251535 TI - Three geographically separate domestications of Asian rice. AB - Domesticated rice (Oryza sativa L.) accompanied the dawn of Asian civilization(1) and has become one of world's staple crops. From archaeological and genetic evidence various contradictory scenarios for the origin of different varieties of cultivated rice have been proposed, the most recent based on a single domestication(2,3). By examining the footprints of selection in the genomes of different cultivated rice types, we show that there were three independent domestications in different parts of Asia. We identify wild populations in southern China and the Yangtze valley as the source of the japonica gene pool, and populations in Indochina and the Brahmaputra valley as the source of the indica gene pool. We reveal a hitherto unrecognized origin for the aus variety in central India or Bangladesh. We also conclude that aromatic rice is a result of a hybridization between japonica and aus, and that the tropical and temperate versions of japonica are later adaptations of one crop. Our conclusions are in accord with archaeological evidence that suggests widespread origins of rice cultivation(1,4). We therefore anticipate that our results will stimulate a more productive collaboration between genetic and archaeological studies of rice domestication, and guide utilization of genetic resources in breeding programmes aimed at crop improvement. PMID- 27251537 TI - Circadian clocks: Who knows where the time goes. PMID- 27251536 TI - The extremophile Nicotiana benthamiana has traded viral defence for early vigour. AB - A single lineage of Nicotiana benthamiana is widely used as a model plant(1) and has been instrumental in making revolutionary discoveries about RNA interference (RNAi), viral defence and vaccine production. It is peerless in its susceptibility to viruses and its amenability in transiently expressing transgenes(2,3). These unparalleled characteristics have been associated both positively and negatively with a disruptive insertion in the RNA-dependent RNA polymerase 1 gene, Rdr1(4-6). For a plant so routinely used in research, the origin, diversity and evolution of the species, and the basis of its unusual abilities, have been relatively unexplored. Here, by comparison with wild accessions from across the spectrum of the species' natural distribution, we show that the laboratory strain of N. benthamiana is an extremophile originating from a population that has retained a mutation in Rdr1 for ~0.8 Myr and thereby traded its defence capacity for early vigour and survival in the extreme habitat of central Australia. Reconstituting Rdr1 activity in this isolate provided protection. Silencing the functional allele in a wild strain rendered it hypersusceptible and was associated with a doubling of seed size and enhanced early growth rate. These findings open the way to a deeper understanding of the delicate balance between protection and vigour. PMID- 27251538 TI - Plant science and the food security agenda. PMID- 27251539 TI - Molecular Ecology: Trading defence for vigour. PMID- 27251540 TI - Tree physiology: Tracking tree carbon gain. PMID- 27251541 TI - Tree growth: Getting back up. PMID- 27251542 TI - Crop domestication: Baked beans. PMID- 27251543 TI - Ecology: Biocrusts buffer drought. PMID- 27251545 TI - Literary plants. PMID- 27251544 TI - Evolution: Symbiotic beginnings. PMID- 27251546 TI - Targeting asparagine and autophagy for pulmonary adenocarcinoma therapy. AB - The mounting number of patients with pulmonary adenocarcinoma (ADCA) is subjected to poor prognosis and heavy mortality, which prompts us to explore new potential therapeutics for lung ADCA. Herein, we reported a novel approach for lung ADCA therapy by abolishing autophagy and asparagine. We demonstrated that deprivation of asparagine by asparaginase could induce significant cytotoxicity and apoptosis in A549 and H1975 cells. During this process, autophagy was triggered by the asparaginase treatment, characterized by the autophagic flux with three main stages including formation of autophagosomes, lysosomes fused with autophagosomes, and degradation of autophagosomes by lysosomes. Importantly, suppression of autophagy could notably enhance the cytotoxicity and accelerate the caspase 3-dependent apoptosis induced by asparaginase. Furthermore, suppression of reactive oxygen species (ROS) could attenuated both the cytotoxicity and autophagy induced by asparaginase, while inhibition of autophagy promoted the generation of ROS in A549 and H1975 cells, indicating the essential role of ROS in asparagine deprivation therapy in lung ADCA cells. Our results demonstrated that targeting cytoprotective autophagy and asparagine could potently kill the ADCA cells, which highlighted a novel approach for lung ADCA therapy in the clinics. PMID- 27251547 TI - Characterization of a novel enzyme-Starmerella bombicola lactone esterase (SBLE) responsible for sophorolipid lactonization. AB - We recently discovered a novel enzyme in the exoproteome of Starmerella bombicola, which is structurally related to Candida antarctica lipase A. A knockout strain for this enzyme does no longer produce lactonic sophorolipids, prompting us to believe that this protein is the missing S. bombicola lactone esterase (SBLE). SBLE catalyzes a rather unusual reaction, i.e., an intramolecular esterification (lactonization) of acidic sophorolipids in an aqueous environment, which raised questions about its activity and mode of action. Here, we report the heterologous production of this enzyme in Pichia pastoris and its purification in a two-step strategy. Purified recombinant SBLE (rSBLE) was used to perform HPLC and liquid chromatography mass spectrometry (LCMS)-based assays with different sophorolipid mixtures. We experimentally confirmed that SBLE is able to perform ring closure of acetylated acidic sophorolipids. This substrate was selected for rSBLE kinetic studies to estimate the apparent values of K m . We established that rSBLE displays optimal activity in the pH range of 3.5 to 6 and has an optimal temperature in the range of 20 to 50 degrees C. Additionally, we generated a rSBLE mutant through site-directed mutagenesis of Ser194 in the predicted active site pocket and show that this mutant is lacking the ability to lactonize sophorolipids. We therefore propose that SBLE operates via the common serine hydrolase mechanism in which the catalytic serine residue is assisted by a His/Asp pair. PMID- 27251548 TI - [Targeting abattoirs to control cystic echinococcosis in Algeria]. AB - Cystic echinococcosis (CE) is an important anthropozoonotic parasitic common in Algeria. The predominant life cycle of E. granulosus is a synanthropic cycle with domestic dogs as definitive hosts and livestock animals as intermediate hosts. Slaughter activity represents a potential source for dogs to access infected offal. The aim of the present study was to determine if the contact between dogs and potentially infected offal was possible in licensed abattoirs. Eighty-one private and public abattoirs located in eastern Algeria were assessed with respect to their level of protection against the intrusion of dogs.We have demonstrated that in 42 % of these abattoirs, dogs could easily come in contact with potentially parasitized offal. The most common incorrect practices were the dumping of offal freely into the environment, the feeding of dogs with offal, and the leaving of unattended offal in an unsealed chamber. Overall, some hazardous practices remained common customs of workers, and enough abattoirs remain non compliant that the cattledog domestic cycle of CE is unlikely to be broken. Hence, some recommended measures to interrupt parasite transmission include the following: recognition of the importance of abattoirs in the maintenance of canine echinococcosis, the controlled and proper disposal of offal, the abolishment of the custom of feeding dogs with infected offal and improvements in the level of health education of abattoir staff. PMID- 27251549 TI - Data-directed RNA secondary structure prediction using probabilistic modeling. AB - Structure dictates the function of many RNAs, but secondary RNA structure analysis is either labor intensive and costly or relies on computational predictions that are often inaccurate. These limitations are alleviated by integration of structure probing data into prediction algorithms. However, existing algorithms are optimized for a specific type of probing data. Recently, new chemistries combined with advances in sequencing have facilitated structure probing at unprecedented scale and sensitivity. These novel technologies and anticipated wealth of data highlight a need for algorithms that readily accommodate more complex and diverse input sources. We implemented and investigated a recently outlined probabilistic framework for RNA secondary structure prediction and extended it to accommodate further refinement of structural information. This framework utilizes direct likelihood-based calculations of pseudo-energy terms per considered structural context and can readily accommodate diverse data types and complex data dependencies. We use real data in conjunction with simulations to evaluate performances of several implementations and to show that proper integration of structural contexts can lead to improvements. Our tests also reveal discrepancies between real data and simulations, which we show can be alleviated by refined modeling. We then propose statistical preprocessing approaches to standardize data interpretation and integration into such a generic framework. We further systematically quantify the information content of data subsets, demonstrating that high reactivities are major drivers of SHAPE-directed predictions and that better understanding of less informative reactivities is key to further improvements. Finally, we provide evidence for the adaptive capability of our framework using mock probe simulations. PMID- 27251550 TI - Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy. AB - The nuclear THO and TREX-2 complexes are implicated in several steps of nuclear mRNP biogenesis, including transcription, 3' end processing and export. In a recent genomic microscopy screen in Saccharomyces cerevisiae for mutants with constitutive stress granules, we identified that absence of THO and TREX-2 complex subunits leads to the accumulation of Pab1-GFP in cytoplasmic foci. We now show that these THO/TREX-2 mutant induced foci ("TT foci") are not stress granules but instead are a mRNP granule containing poly(A)(+) mRNA, some mRNP components also found in stress granules, as well several proteins involved in mRNA 3' end processing and export not normally seen in stress granules. In addition, TT foci are resistant to cycloheximide-induced disassembly, suggesting the presence of mRNPs impaired for entry into translation. THO mutants also exhibit defects in normal stress granule assembly. Finally, our data also suggest that TT foci are targeted by autophagy. These observations argue that defects in nuclear THO and TREX-2 complexes can affect cytoplasmic mRNP function by producing aberrant mRNPs that are exported to cytosol, where they accumulate in TT foci and ultimately can be cleared by autophagy. This identifies a novel mechanism of quality control for aberrant mRNPs assembled in the nucleus. PMID- 27251551 TI - Physiological evidence for plasticity in glycolate/glycerate transport during photorespiration. AB - Photorespiration recycles fixed carbon following the oxygenation reaction of Ribulose, 1-5, carboxylase oxygenase (Rubisco). The recycling of photorespiratory C2 to C3 intermediates is not perfectly efficient and reduces photosynthesis in C3 plants. Recently, a plastidic glycolate/glycerate transporter (PLGG1) in photorespiration was identified in Arabidopsis thaliana, but it is not known how critical this transporter is for maintaining photorespiratory efficiency. We examined a mutant deficient in PLGG1 (plgg1-1) using modeling, gas exchange, and Rubisco biochemistry. Under low light (under 65 MUmol m(-2) s(-1) PAR), there was no difference in the quantum efficiency of CO2 assimilation or in the photorespiratory CO2 compensation point of plgg1-1, indicating that photorespiration proceeded with wild-type efficiency under sub-saturating light irradiances. Under saturating light irradiance (1200 MUmol m(-2) s(-1) PAR), plgg1-1 showed decreased CO2 assimilation that was explained by decreases in the maximum rate of Rubisco carboxylation and photosynthetic linear electron transport. Decreased rates of Rubisco carboxylation resulted from probable decreases in the Rubisco activation state. These results suggest that glycolate/glycerate transport during photorespiration can proceed in moderate rates through an alternative transport process with wild-type efficiencies. These findings also suggest that decreases in net CO2 assimilation that occur due to disruption to photorespiration can occur by decreases in Rubisco activity and not necessarily decreases in the recycling efficiency of photorespiration. PMID- 27251552 TI - Intraventricular thrombolysis after endovascular treatment of a ruptured arteriovenous malformation. AB - Intraventricular haemorrhage (IVH) secondary to arteriovenous malformation (AVM) rupture carries significant morbidity and mortality. External ventricular drainage of IVH is frequently complicated by thrombus formation within the ventricular catheter and therefore often unsuccessful at treating hydrocephalus in this setting. Intraventricular administration of recombinant tissue-type plasminogen activator (rtPA) has proved successful in the treatment of spontaneous panventricular haemorrhage. However, usage of rtPA is contraindicated in the setting of a ruptured AVM or aneurysm in which the bleeding source has not been secured. There are only a few reports of intraventricular thrombolysis in the treatment of IVH from AVM rupture. We present the case of successful application of rtPA to treat IVH after endovascularly securing the haemorrhage site of the AVM. Intraventricular thrombolysis remains an option for the treatment of IVH in the setting of AVM rupture and should be considered on a case by-case basis. PMID- 27251553 TI - Development of an Emergency Medicine Simulation Fellowship Consensus Curriculum: Initiative of the Society for Academic Emergency Medicine Simulation Academy. AB - OBJECTIVES: There is currently no consolidated list of existing simulation fellowship programs in emergency medicine (EM). In addition, there are no universally accepted or expected standards for core curricular content. The objective of this project is to develop consensus-based core content for EM simulation fellowships to help frame the critical components of such training programs. METHODS: This paper delineates the process used to develop consensus curriculum content for EM simulation fellowships. EM simulation fellowship curricula were collected. Curricular content was reviewed and compiled by simulation experts and validated utilizing survey methodology, and consensus was obtained using a modified Delphi methodology. RESULTS: Fifteen EM simulation fellowship curricula were obtained and analyzed. Two rounds of a modified Delphi survey were conducted. The final proposed core curriculum content contains 47 elements in nine domains with 14 optional elements. CONCLUSION: The proposed consensus content will provide current and future fellowships a foundation on which to build their own specific and detailed fellowship curricula. Such standardization will ultimately increase the transparency of training programs for future trainees and potential employers. PMID- 27251554 TI - Fish allergy in patients with parvalbumin-specific immunoglobulin E depends on parvalbumin content rather than molecular differences in the protein among fish species. AB - Allergenic characteristics of purified parvalbumins from different fish species have not been thoroughly investigated. We revealed that purified parvalbumins from nine different fish species have identical IgE-reactivities and high cross reactivities. We also showed that fish allergenicity is associated with the parvalbumin content of the fish species, rather than species-specific differences in the molecular characteristics of the individual parvalbumin proteins. PMID- 27251555 TI - Parathyroid adenomas: a potential source of pitfalls for thyroid FNA cytology. PMID- 27251556 TI - Economic evaluation of the breast cancer screening programme in the Basque Country: retrospective cost-effectiveness and budget impact analysis. AB - BACKGROUND: Breast cancer screening in the Basque Country has shown 20 % reduction of the number of BC deaths and an acceptable overdiagnosis level (4 % of screen detected BC). The aim of this study was to evaluate the breast cancer early detection programme in the Basque Country in terms of retrospective cost effectiveness and budget impact from 1996 to 2011. METHODS: A discrete event simulation model was built to reproduce the natural history of breast cancer (BC). We estimated for lifetime follow-up the total cost of BC (screening, diagnosis and treatment), as well as quality-adjusted life years (QALY), for women invited to participate in the evaluated programme during the 15-year period in the actual screening scenario and in a hypothetical unscreened scenario. An incremental cost-effectiveness ratio was calculated with the use of aggregated costs. Besides, annual costs were considered for budget impact analysis. Both population level and single-cohort analysis were performed. A probabilistic sensitivity analysis was applied to assess the impact of parameters uncertainty. RESULTS: The actual screening programme involved a cost of 1,127 million euros and provided 6.7 million QALYs over the lifetime of the target population, resulting in a gain of 8,666 QALYs for an additional cost of 36.4 million euros, compared with the unscreened scenario. Thus, the incremental cost-effectiveness ratio was 4,214?/QALY. All the model runs in the probabilistic sensitivity analysis resulted in an incremental cost-effectiveness ratio lower than 10,000?/QALY. The screening programme involved an increase of the annual budget of the Basque Health Service by 5.2 million euros from year 2000 onwards. CONCLUSIONS: The BC screening programme in the Basque Country proved to be cost effective during the evaluated period and determined an affordable budget impact. These results confirm the epidemiological benefits related to the centralised screening system and support the continuation of the programme. PMID- 27251558 TI - Isolation of culturable aerobic bacteria and evidence of Kerstersia gyiorum from the blowhole of captive Yangtze finless porpoises. AB - Bacterial respiratory illnesses are problematic in aquatic mammals such as the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis; YFP), which is now at a critically endangered status. Yet little is known about the bacteria inhabiting the respiratory tract of YFPs. In this study, we preliminarily characterized the culturable aerobic bacteria from blow samples of captive YFPs. The bacterial diversity was assessed through cultivation by direct exhalation onto Columbia blood agar plates and identification of representative isolates through 16S rRNA gene sequence analysis. In total, eleven bacterial species belonging to four phyla Proteobacteria (71 %), Firmicutes (25 %), Bacteroidetes (3 %) and Actinobacteria (1 %) were identified. Most of these isolates were opportunistic pathogens found in respiratory illnesses in humans and animals. We also reported the first case of Kerstersia gyiorum isolated from an animal. This work provides a preliminary assessment of the bacteria present in the respiratory tract of captive YFPs, which will be an important first step in elucidating the roles of normal microbiota in maintaining respiratory health of YFPs. This study also points out the necessity of future long-term monitoring of blowhole microorganisms in the YFPs and making emergency preparedness plans for respiratory tract infections. These measures can aid in assessing the pathogenic risk of the critically endangered YFP populations. PMID- 27251557 TI - Genomic survey sequencing for development and validation of single-locus SSR markers in peanut (Arachis hypogaea L.). AB - BACKGROUND: Single-locus markers have many advantages compared with multi-locus markers in genetic and breeding studies because their alleles can be assigned to particular genomic loci in diversity analyses. However, there is little research on single-locus SSR markers in peanut. Through the de novo assembly of DNA sequencing reads of A. hypogaea, we developed single-locus SSR markers in a genomic survey for better application in genetic and breeding studies of peanut. RESULTS: In this study, DNA libraries with four different insert sizes were used for sequencing with 150 bp paired-end reads. Approximately 237 gigabases of clean data containing 1,675,631,984 reads were obtained after filtering. These reads were assembled into 2,102,446 contigs with an N50 length of 1,782 bp, and the contigs were further assembled into 1,176,527 scaffolds with an N50 of 3,920 bp. The total length of the assembled scaffold sequences was 2.0 Gbp, and 134,652 single-locus SSRs were identified from 375,180 SSRs. Among these developed single locus SSRs, trinucleotide motifs were the most abundant, followed by tetra-, di-, mono-, penta- and hexanucleotide motifs. The most common motif repeats for the various types of single-locus SSRs have a tendency to be A/T rich. A total of 1,790 developed in silico single-locus SSR markers were chosen and used in PCR experiments to confirm amplification patterns. Of them, 1,637 markers that produced single amplicons in twelve inbred lines were considered putative single locus markers, and 290 (17.7 %) showed polymorphisms. A further F2 population study showed that the segregation ratios of the 97 developed SSR markers, which showed polymorphisms between the parents, were consistent with the Mendelian inheritance law for single loci (1:2:1). Finally, 89 markers were assigned to an A. hypogaea linkage map. A subset of 100 single-locus SSR markers was shown to be highly stable and universal in a collection of 96 peanut accessions. A neighbor joining tree of this natural population showed that genotypes have obviously correlation with botanical varieties. CONCLUSIONS: We have shown that the detection of single-locus SSR markers from a de novo genomic assembly of a combination of different-insert-size libraries is highly efficient. This is the first report of the development of genome-wide single-locus markers for A. hypogaea, and the markers developed in this study will be useful for gene tagging, sequence scaffold assignment, linkage map construction, diversity analysis, variety identification and association mapping in peanut. PMID- 27251559 TI - Adoption Factors of the Electronic Health Record: A Systematic Review. AB - BACKGROUND: The Health Information Technology for Economic and Clinical Health (HITECH) was a significant piece of legislation in America that served as a catalyst for the adoption of health information technology. Following implementation of the HITECH Act, Health Information Technology (HIT) experienced broad adoption of Electronic Health Records (EHR), despite skepticism exhibited by many providers for the transition to an electronic system. A thorough review of EHR adoption facilitator and barriers provides ongoing support for the continuation of EHR implementation across various health care structures, possibly leading to a reduction in associated economic expenditures. OBJECTIVE: The purpose of this review is to compile a current and comprehensive list of facilitators and barriers to the adoption of the EHR in the United States. METHODS: Authors searched Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE, 01/01/2012-09/01/2015, core clinical/academic journals, MEDLINE full text, and evaluated only articles germane to our research objective. Team members selected a final list of articles through consensus meetings (n=31). Multiple research team members thoroughly read each article to confirm applicability and study conclusions, thereby increasing validity. RESULTS: Group members identified common facilitators and barriers associated with the EHR adoption process. In total, 25 adoption facilitators were identified in the literature occurring 109 times; the majority of which were efficiency, hospital size, quality, access to data, perceived value, and ability to transfer information. A total of 23 barriers to adoption were identified in the literature, appearing 95 times; the majority of which were cost, time consuming, perception of uselessness, transition of data, facility location, and implementation issues. CONCLUSIONS: The 25 facilitators and 23 barriers to the adoption of the EHR continue to reveal a preoccupation on cost, despite incentives in the HITECH Act. Limited financial backing and outdated technology were also common barriers frequently mentioned during data review. Future public policy should include incentives commensurate with those in the HITECH Act to maintain strong adoption rates. PMID- 27251560 TI - Downregulation of Checkpoint Protein Kinase 2 in the Urothelium of Healthy Male Tobacco Smokers. AB - With this letter to the editor we present for the first time a study on CHEK2 expression in normal urothelium of healthy male smokers, former smokers and non smokers. We could show a statistically significant downregulation of this DNA repair gene in current smokers compared to non-smokers, suggesting that smoking downregulates CHEK2 in normal urothelium, probably associated with an early step in carcinogenesis of urothelial bladder carcinoma. PMID- 27251561 TI - Iron Deficiency in India. PMID- 27251562 TI - Organizing pneumonia as the first manifestation of anti-synthetase syndrome. AB - BACKGROUND: Anti-synthetase syndrome associated interstitial lung disease can occur either simultaneously, before, or after the development of polymyositis/dermatomyositis. Histology of interstitial lung disease can be nonspecific interstitial pneumonia, usual interstitial pneumonia, diffuse alveolar damage, organizing pneumonia. Organizing pneumonia associated anti synthetase syndrome is a rare finding especially as the first manifestation. CASE PRESENTATION: We report a 41 year old male patient who presented with organizing pneumonia and 2 years following the onset, developed polymyositis with anti-JO-1 antibody positivity. CONCLUSION: It is important to screen patients with organizing pneumonia for anti-synthetase syndrome which can be manifested later. PMID- 27251563 TI - Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics. AB - BACKGROUND: The cytoprotective effect of heme oxygenase (HO)-1 in various forms of renal glomerular injury is established. However, little is known on the role of HO-1 in preserving glomerular structural/functional integrity in the absence of injury. The present study addressed this question in HO-1-deficient rats. METHODS: HO-1-deficient rats were generated using zinc finger nuclease-mediated HO-1 gene (Hmox1) disruption and studied. Glomeruli were isolated from HO-1 deficient (Hmox1-/-) rats and their wild type (WT) littermates for proteomic analysis. RESULTS: Glomerular lesions were characterized and differentially expressed proteins important for preserving integrity of the glomerular filtration barrier were identified. HO-1-deficient (Hmox1-/-) rats developed albuminuria with decreased glomerular filtration rate. In albuminuric rats, there were lesions resembling focal and segmental glomerulosclerosis (FSGS). Western blot analysis of the integral slit diaphragm proteins, nephrin and podocin revealed a significant decrease in nephrin, with no change in podocin. Proteomic analysis of glomerular protein lysates from Hmox1-/- and WT rats revealed differential expression of proteins previously linked with FSGS pathogenesis. Specifically, alpha-actinin-4, actin related protein 3, cytokeratins and novel candidates including transgelin-2 and lamins. Bioinformatic analysis predicted the upregulation of pathways implicated in platelet aggregation and fibrin clot formation. CONCLUSION: HO-1 is a putative regulator of proteins important in preserving glomerular structural stability and integrity, and in minimizing the activity of proinflammatory pathways. PMID- 27251564 TI - Well-defined palladium(0) complexes bearing N-heterocyclic carbene and phosphine moieties: efficient catalytic applications in the Mizoroki-Heck reaction and direct C-H functionalization. AB - Two series of well-defined palladium(0) complexes with phosphine-functionalized N heterocyclic carbene ligands were prepared. These complexes featured six- and seven-membered chelate rings in the two series. Among the seven-membered chelate complexes, those featuring the PCy2 moiety exhibited observable fluxional behavior on the NMR time scale, corresponding to the interchange between two sets of conformations. Most of these novel complexes were successfully structurally characterized by single-crystal X-ray diffraction studies. These two series of palladium(0) complexes were tested for their potential catalytic applications in two mechanistically distinct reactions, namely, Mizoroki-Heck coupling and direct C-H functionalization reactions. One of the six-membered chelate complexes was found to be an efficient pre-catalyst for mediating the coupling reactions between aryl chlorides and alkenes. The palladium(0) complex could also be effectively applied in the direct C-H functionalization reactions of aryl bromides with 1,2-dimethylimidazole. PMID- 27251565 TI - Iatrogenic injury of the lateral meniscus anterior insertion following anterior cruciate ligament reconstruction: A case report. PMID- 27251566 TI - Sustained Inflation and Its Role in the Delivery Room Management of Preterm Infants. AB - A noninvasive approach in the delivery room in place of intubation and mechanical ventilation can reduce rates of bronchopulmonary dysplasia and death. Nevertheless, the rate of nasal continuous positive airway pressure failure still remains high. In order to prevent lung injury and to enhance the success of continuous positive airway pressure, sustained inflation (administration by face mask or nasopharyngeal tube of a high peak pressure of 20-25 cm H2O, maintained for 10-15 s) has been recently proposed to establish an early and efficient functional residual capacity in the delivery room. Sustained inflation is an intriguing therapy, although the results of clinical trials are controversial in terms of respiratory outcomes. A critical role in the success of sustained inflation could be the presence of open or closed glottis and the contribution of spontaneous breathing that allows air to enter the lungs during the maneuver. Recent neonatal resuscitation guidelines suggest that sustained inflation may be considered in individual clinical circumstances or research settings. PMID- 27251567 TI - The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization. AB - Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30-90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm(2) to flat-shaped protrusions at 8,000 per cm(2), whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination. PMID- 27251568 TI - Clinical importance of change in physical activity after endovascular treatment combined with exercise training in patients with peripheral arterial disease. AB - We aimed to investigate the characteristics of changes in amount of physical activity of patients with peripheral arterial disease (PAD) before/after endovascular treatment (EVT) combined with exercise training. Twenty-two patients with peripheral arterial disease at stage-II of the Fontaine classification who received EVT combined with exercise training were included in this study. A tri axial accelerometer was used to record physical activity every day from the day before surgery to 3 months after discharge from hospital. The mean number of walking steps before surgery was 2664 steps (611 steps-5404 steps), whereas those after surgery was 3393 (567 steps-7578 steps). Ankle Brachial Index (from 0.69 to 1.03; p < 0.001), maximum walking distance (from 728.2 to 1271.8 m; p < 0.05) and Vascu-QOL (from 98.9 to 137.9; p < 0.01) showed improvement between before and after surgery. Physical activity of patients with PAD was still low at 3 months after surgery even though walking ability, QOL, and self-efficacy were improved after EVT combined with exercise training. Among the 22 patients, the number of walking steps increased in 17 of them and decreased in 5 of them. Compared with the patients in the increased-steps group, those in the decreased-steps group were significantly older (p < 0.05), and had a significantly higher cardiovascular event rate within the first 3 months after surgery (p < 0.05). These results suggested that, not only the improvement of walking ability, but increase in physical activity after EVT combined with exercise training is also important for short-term prognosis. PMID- 27251569 TI - Transcatheter aortic valve replacement in nonagenarians: early and intermediate outcome from the OBSERVANT study and meta-analysis of the literature. AB - The purpose of this study was to evaluate the outcome of nonagenarians after transcatheter aortic valve replacement (TAVR) from the OBSERVANT study and to pool the results of the literature on this topic. Aortic stenosis is the most common acquired valvular heart disease in the Western countries, and its prevalence is linked to the phenomenon of population aging. TAVR can be considered as a wise approach to treat nonagenarians, but data on its safety and effectiveness are scarce. Data on 80 patients aged >90 years who underwent TAVR from OBSERVANT study were analyzed. A systematic review and meta-analysis of published data were performed. Thirty-day mortality in the OBSERVANT series was 6.3 %. None of these patients experienced stroke. Permanent pacemaker implantation was necessary in 20 % of patients. Paravalvular regurgitation was observed in 57.5 %. Survival at 1, 2, and 3 years was 79.6, 71.9, and 61.5 %. Ten series provided data on 1227 nonagenarians who underwent TAVR. Pooled 30-day mortality rate was 7.1 %, stroke 2.8 %, vascular access complication 8.8 %, and permanent pacemaker implantation 10.6 %. Paravalvular regurgitation was observed in 60.1 % of patients. Pooled 1-, 2-, and 3-year survival rates were 79.2, 68.2, and 55.6 %. Transapical TAVR was associated with a significantly higher risk of early mortality compared with transfemoral TAVR. The results of OBSERVANT study and aggregate data meta-analysis suggest that in nonagenarians, TAVR is associated with low postoperative morbidity and excellent intermediate survival. Transapical TAVR in these very elderly is associated with high postoperative mortality. PMID- 27251570 TI - Serum carboxy-terminal telopeptide of type I collagen (I-CTP) is predictive of clinical outcome in peripheral artery disease patients following endovascular therapy. AB - Peripheral artery disease (PAD) is a risk factor for the development of heart failure and mortality. The serum levels of carboxy-terminal telopeptide of type I collagen (I-CTP), a marker for collagen degradation derived from the extracellular matrix of vascular and myocardial tissue, is reportedly a useful marker for cardiac events in patients with heart disease. However, it remains unclear whether I-CTP can predict poor clinical outcome in patients with PAD. Serum I-CTP was measured in 246 consecutive PAD patients who underwent endovascular therapy. Patients were prospectively followed during a median follow up period of 887 days with the end points of major adverse cardiovascular events (MACE). I-CTP was significantly higher in patients with critical limb ischemia than those without. A multivariate Cox proportional hazard analysis revealed that I-CTP was an independent predictor of MACE after adjusting for confounding factors. Patients were stratified into three groups based on I-CTP level tertile, and those with third tertile had higher levels of brain natriuretic peptide levels and high-sensitivity C-reactive protein compared to the other two groups. Kaplan-Meier analysis demonstrated that patients in the highest tertile of I-CTP also had the greatest risk of MACE. The net reclassification index significantly improved with the addition of I-CTP to basic predictors. I-CTP is a reliable marker and indicator for MACE in patients with PAD. PMID- 27251572 TI - Laparoscopic caudal approach for a small hepatocellular carcinoma located in the paracaval portion of a cirrhotic liver. AB - Resection of a tumor located in the paracaval portion of the liver, without sacrificing other parts of the liver, is surgically challenging. Here, we describe using a laparoscopic caudal approach for a small hepatocellular carcinoma located in the paracaval portion. It is the first case using the laparoscopic caudal approach to be reported in the literature. Compared with the conventional approaches, this procedure can minimize both surgical invasiveness and the volume of liver parenchyma to be resected. In addition, the laparoscopic view is suitable for this procedure. The laparoscopic caudal approach can be a safe procedure with minimal invasiveness for a small paracaval tumor, particularly in patients with liver cirrhosis. PMID- 27251571 TI - Zuogui Wan rescues the high-glucose-induced damaging effects on early embryo development. AB - BACKGROUND: High concentration of glucose in culture medium affects the developmental process and the quality of the pre-implantation embryo. This study examined the effects of Zuogui Wan (ZGW) supplementation on early embryo development cultured in high-glucose medium. METHODS: Embryos were cultured in high-glucose medium with or without ZGW supplementation. Developmental rate and competence was evaluated by cleavage rate, blastocyst rate, and blastocyst total cell number, reactive oxygen species (ROS) level, glutathione (GSH) concentration, and metabolome were also measured to determine the effect of ZGW on embryo development at the cellular level. RESULTS: Compared with the vehicle group, supplementation of 0.01 % (v/v) ZGW to high-glucose medium significantly increased cleavage rate (80.1 +/- 1.0 % vs 72.1 +/- 1.3 %), blastocyst rate (50.5 +/- 1.0 % vs 41.3 +/- 1.7 %), and blastocyst total cell number (63.2 +/- 2.2 vs 57.2 +/- 1.6). ROS level was lower and GSH concentration in blastocysts was higher in ZGW-treated group. Metabolomic analysis found that the ratio of glucose to succinic acid and glucose to fumaric acid were lower in the ZGW-treated group . CONCLUSIONS: Developmental rates of zygotes in high-glucose culture medium were significantly lower than those in regular culture medium. ZGW supplementation significantly improved embryo development and quality in high-glucose medium. Supplementing ZGW in high-glucose medium also significantly increased total cell number and GSH concentration but decreased ROS level in blastocysts likely by modifying metabolic profile during embryo development. Together, these data suggest that supplementation of ZGW rescues high-glucose-induced detrimental effects on pre-implantation embryo development. PMID- 27251574 TI - G-Quadruplexes with Tetra(ethylene glycol)-Modified Deoxythymidines are Resistant to Nucleases and Inhibit HIV-1 Reverse Transcriptase. AB - G-quadruplex formation in virally encoded templates arrests reverse transcription. Methods to stabilize this structure are promising for antiviral approaches. To stabilize G-quadruplex formation, deoxythymidines were modified with tetra(ethylene glycol) (TEG). The TEG-modified G-quadruplexes were stabilized significantly relative to unmodified DNA. In the presence of a TEG modified oligonucleotide that is capable of forming an intermolecular G quadruplex with a template containing a hu- man immunodeficiency virus-1 sequence, reverse transcription was inhibited by more than 70 % relative to the reaction in the absence of the TEG-modified oligonucleotide. Moreover, the TEG modified deoxythymidines protected the DNA oligonucleotide from degradation by various nucleases in human serum. Thus, DNA oligonucleotides modified with TEG have potential in therapeutic applications. PMID- 27251573 TI - Immuno-targeting the multifunctional CD38 using nanobody. AB - CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10(-11) molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma. PMID- 27251575 TI - The dark side of street lighting: impacts on moths and evidence for the disruption of nocturnal pollen transport. AB - Among drivers of environmental change, artificial light at night is relatively poorly understood, yet is increasing on a global scale. The community-level effects of existing street lights on moths and their biotic interactions have not previously been studied. Using a combination of sampling methods at matched-pairs of lit and unlit sites, we found significant effects of street lighting: moth abundance at ground level was halved at lit sites, species richness was >25% lower, and flight activity at the level of the light was 70% greater. Furthermore, we found that 23% of moths carried pollen of at least 28 plant species and that there was a consequent overall reduction in pollen transport at lit sites. These findings support the disruptive impact of lights on moth activity, which is one proposed mechanism driving moth declines, and suggest that street lighting potentially impacts upon pollination by nocturnal invertebrates. We highlight the importance of considering both direct and cascading impacts of artificial light. PMID- 27251576 TI - Frequent Nek1 overexpression in human gliomas. AB - Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients' poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87 MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ resistance. PMID- 27251577 TI - Concurrent enhancement of percolation and synchronization in adaptive networks. AB - Co-evolutionary adaptive mechanisms are not only ubiquitous in nature, but also beneficial for the functioning of a variety of systems. We here consider an adaptive network of oscillators with a stochastic, fitness-based, rule of connectivity, and show that it self-organizes from fragmented and incoherent states to connected and synchronized ones. The synchronization and percolation are associated to abrupt transitions, and they are concurrently (and significantly) enhanced as compared to the non-adaptive case. Finally we provide evidence that only partial adaptation is sufficient to determine these enhancements. Our study, therefore, indicates that inclusion of simple adaptive mechanisms can efficiently describe some emergent features of networked systems' collective behaviors, and suggests also self-organized ways to control synchronization and percolation in natural and social systems. PMID- 27251578 TI - A pilot investigation of the potential for incorporating lifelog technology into executive function rehabilitation for enhanced transfer of self-regulation skills to everyday life. AB - The objective of the study was to identify the potential target and effect size of goal management training (GMT) enhanced with life-logging technology compared with standard GMT on a range of possible primary outcomes reflecting cognitive and ecological aspects of executive functioning and quality of life. Sixteen patients with acquired brain injury involving executive dysfunction were randomly allocated to one of the two interventions: seven weeks of GMT (n = 8), or seven weeks of GMT+Lifelog (n = 8). Outcome measures included a battery of executive function tests, the Dysexecutive Questionnaire (DEX) and the Quality of Life after Brain Injury scale (QOLIBRI), measured pre- and post-interventions. Within group changes were assessed with related-samples t-tests and estimation of effect sizes. GMT+Lifelog was associated with significant changes, of medium to large effect size, in response inhibition (Stroop), multitasking (Strategy Application and Multiple Errand tests), DEX Intentionality and Positive Affect subscales and QOLIBRI Daily Life and Autonomy, subscales. GMT alone was associated with significant changes of overall quality of life. It was concluded that GMT+Lifelog holds promise to optimise the impact of GMT on executive dysfunction and quality of life. PMID- 27251579 TI - Very mild features of dysequilibrium syndrome associated with a novel VLDLR missense mutation. AB - Dysequilibrium syndrome (DES) is a non-progressive congenital ataxia characterized by severe intellectual deficit, truncal ataxia and markedly delayed, quadrupedal or absent ambulation. Recessive loss-of-function mutations in the very low density lipoprotein receptor (VLDLR) gene represent the most common cause of DES. Only two families have been reported harbouring homozygous missense mutations, both with a similarly severe phenotype. We report an Italian girl with very mild DES caused by the novel homozygous VLDLR missense mutation p.(C419Y). This unusually benign phenotype possibly relates to a less disruptive effect of the mutation, falling within a domain (EGF-B) not predicted as crucial for the protein function. PMID- 27251580 TI - Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy. AB - Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of <0.05. Four genes and seven RNA probes were with prognostic value for post operative seizure-free outcome. Gene expression associated with seizure-free outcome included relative down-regulation of zinc finger protein 852 (ZNF852), CUB domain-containing protein 2 (CDCP2), proline-rich transmembrane protein 1 (PRRT1), hypothetical LOC440200 (FLJ41170), RNA probe 8047763, RNA probe 8126238, RNA probe 8113489, RNA probe 8092883, RNA probe 7935228, RNA probe 806293, and RNA probe 8104131. This study describes the predictive value of temporal cortical gene expression for seizure-free outcome after ATL/AH. Four genes and seven RNA probes were found to predict post-operative seizure-free outcome. Future prospective investigation of these genes and probes in human brain tissue and blood could establish new biomarkers predictive of seizure outcome following ATL/AH. PMID- 27251581 TI - Consummatory succesive positive contrast produced by the downshift of an aversive solution in infant rats. AB - Subjects trained in successive positive contrast are usually given an appetitive stimulus of relatively low quality during a pre-shift, followed by exposure to a significantly greater quality of the same stimulus. Enhanced responsiveness to the high-quality stimulus during the post-shift phase, compared to a control group that receives the superior reward in both phases, is taken as an index of successive positive contrast. Successive positive contrast reports are rare, probably due to performance limitations inherent to the experimental protocols available. We exposed infant rats (14 days old at the start of training) to .1% or .01% quinine during 4, 10 min, trials (pre-shift phase). All animals were then given two trials of exposure to .01% quinine (post-shift phase). During the pre shift the level of intake was greater in pups stimulated with the relatively less aversive .01% quinine solution. These animals also exhibited, compared to those stimulated with .1% quinine, lower emission of the aversive response paw treading. During the post-shift phase, the group that had been exposed to .1% quinine exhibited significantly greater intake of .01% quinine, along with a reduction in the emission of paw treading and an enhancement in paw licking, an ingestive, appetitive response. Altogether, the evidence is suggestive of the emergence of consummatory successive positive contrast during the second week of life of the rat. To our knowledge, this is the first evidence of positive contrast using an aversive solution. PMID- 27251582 TI - Effect of 3,4-diaminopyridine at the murine neuromuscular junction. AB - INTRODUCTION: We investigated the effects of 3,4-diaminopyridine (3,4-DAP) and its acetylated metabolite, N-(4-amino-pyridin-3-yl) acetamide (3-Ac), at the mammalian neuromuscular junction. METHODS: Quantal release of acetylcholine was studied in diaphragm muscles of mice, using in vitro intracellular microelectrode recordings. RESULTS: Under conditions of low probability of release, 3,4-DAP produced a 1,000% increase in quantal release, but 3-Ac had no effect. Under conditions of normal probability of release, the effect of 3,4-DAP was modest and limited by concurrent depletion of synaptic vesicles, especially with high concentrations of 3,4-DAP and high frequencies of nerve stimulation. CONCLUSIONS: These findings predict 3,4-DAP is most effective in conditions with low probability of quantal release, such as Lambert-Eaton myasthenic syndrome. A beneficial effect is also expected in disorders of neuromuscular transmission in which the effect of 3,4-DAP on quantal release is not limited by depletion of synaptic vesicles, such as postsynaptic congenital myasthenic syndromes. Muscle Nerve, 2016 Muscle Nerve 55: 223-231, 2017. PMID- 27251583 TI - Lack of significant bleeding despite large acute rivaroxaban overdose confirmed with whole blood concentrations. AB - BACKGROUND: Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone. CASE REPORT: A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940 mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2 s; INR 7.2; aPTT, 55.7 s; BUN 28 mg/dL; and creatinine 1.2 mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160 ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization. CONCLUSION: In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient. PMID- 27251584 TI - Flexibilities of isoindoline-derived spin labels for nucleic acids by orientation selective PELDOR. AB - Pulsed electron electron double resonance experiments with rigid spin labels can reveal very detailed information about the structure and conformational flexibility of nucleic acid molecules. On the other hand, the analysis of such data is more involved the distance and orientation information encoded in the time domain data need to be extracted and separated. In this respect studies with different spin labels with variable internal mobility are interesting and can help to unambiguously interpret the EPR data. Here orientation selective multi frequency/multi-field 4-pulse PELDOR/DEER experiments with three recently presented semi-rigid or conformationally unambiguous isoindoline-derived spin labels were performed and simulated quantitatively by taking the spin label dynamics into account. PELDOR measurements were performed for a 20-mer dsDNA with two spin labels attached to two defined uridine derivatives. Measurements were recorded for different spin label positions within the double helical strand and for different magnetic field strengths. The experimental data sets were compared with simulations, taking into account the previously described dsDNA dynamics and the internal motions of the spin label itself, which had shown distinct differences between the three spin labels used. The (ExIm)U spin label shows a free rotation around a single bond, which averages out orientation effects, without influencing the distance distribution as it can occur in other spin labels. The (Im)U and (Ox)U spin label, on the other hand, show distinct orientation behaviour with minimal intrinsic motion. We could quantitatively determine this internal motion and demonstrate that the conformational dynamics of the nucleic acid and the spin label can be well separated by this approach. PMID- 27251585 TI - Downregulation of CXCR4 Expression and Functionality After Zoledronate Exposure in Canine Osteosarcoma. AB - BACKGROUND: The establishment and progression of metastases remains the life limiting factor for dogs diagnosed with osteosarcoma (OS). The pattern of metastases is likely regulated through interactions between chemokine receptors and chemokines, and perturbations in these signaling cascades responsible for cytoskeletal organization and directional migration have the potential to alter metastatic cell trafficking behaviors. HYPOTHESIS: Zoledronate will impair directional migration of OS cells through downregulation of chemokine (C-X-C motif) receptor 4 (CXCR4) expression and functionality. SAMPLES: Nineteen archived tumor specimens and plasma from 20 dogs with OS. METHODS: Prospectively, the expressions of CXCR4 were studied in OS cell lines and spontaneous tumor samples. The effect of zoledronate on CXCR4 expression and functionality was investigated by characterizing responses in 3 OS cell lines. In 19 OS specimens and 20 dogs with OS, changes in CXCR4 expression and circulating CXCR4 concentrations were characterized in response to zoledronate therapy respectively. RESULTS: All canine OS cells express CXCR4, and zoledronate reduces CXCR4 expression and functionality by 27.7% (P < .0001), through augmented proteasome degradation and reduced prenylation of heterotrimeric G-proteins in 33% of tumor cell lines evaluated. In OS-bearing dogs, zoledronate reduces CXCR4 expressions by 40% within the primary tumor compared to untreated controls (P = .03) and also decreases the circulating concentrations of CXCR4 in 18 of 20 dogs with OS. CONCLUSIONS AND CLINICAL IMPORTANCE: Zoledronate can alter CXCR4 expression and functionality in OS cells, and consequent perturbations in CXCR4 intracellular signaling cascades might influence patterns of metastases. PMID- 27251586 TI - Old World Leishmaniasis: an ancient disease with nonstandardized microscopic and clinical classifications. AB - BACKGROUND: Microscopic and clinical classifications of cutaneous leishmania have been set in the 1980s. Since then, they have been used invariably. Lebanon, a nonendemic country, is suffering from a leishmaniasis epidemic because of the massive population influx from endemic Syria. DESIGN: Patients diagnosed and speciated with leishmania (n = 169) using molecular and microscopic analysis were studied. General demographic data, microscopic data [Ridley's pattern (RP), microscopic pattern, Parasitic Index (PI)] and clinical stage were documented. Clinical score was scored as: 1: inflammatory; 2: proliferative/reorganization; 3: healed phases. The three patterns were studied in comparison to the lesion age and PI. RESULTS: At low PI, the clinical score and microscopic pattern showed healing scores (scores 3 and 4, respectively). In contrast, RP showed variable distribution at low PI. The same pattern is noted when correlating the different patterns with high PI. In comparison to lesion age, none of the three patterns showed the predicted linear correlation with lesion progression. CONCLUSION: In the studied population, the previously adopted classifications did not correlate with the disease progression. Such findings may raise the possibility of evolving disease. The proposed clinical and microscopic patterns showed better correlation with the disease progression. PMID- 27251587 TI - Botanical and biological pesticides elicit a similar Induced Systemic Response in tomato (Solanum lycopersicum) secondary metabolism. AB - Natural pesticides have attracted substantial interest due to the increase in organic agriculture and enhanced attention to environmental pollution. Plant Growth Promoting Bacteria (PGPB) are applied for both disease control and growth enhancement; PGPBs are known to elicit Induced Systemic Response (ISR) in plants. However, less is known about the effect of botanical pesticides, such as the azadirachtin-containing neem extracts, on plant metabolism. This study aimed to investigate the effects of foliar application of the above-mentioned natural pesticides on the metabolic profiling of tomato. Leaf application of Bacillus subtilis fostered Induced Systemic Resistance (ISR) in treated plants via the Jasmonic acid pathway, and enhanced production of secondary metabolites such as flavonoids, phytoalexins and auxins. Changes in sterols and terpenes, as well as an increase in glucosinolates were also observed. Interestingly, azadirachtin treated tomatoes also showed an increase in ISR and our results revealed that most of the enriched metabolites are shared with a B. subtilis treatment, suggesting conserved biochemical responses. These (un)expected findings indicate that plants are not insensitive to application of natural pesticide and while Azadirachtin is applied as a direct pesticide, it also stimulates a defense response in tomatoes very similar to B. subtilis induced ISR. PMID- 27251588 TI - Androgen receptor GGC repeat might be more involved than CAG repeat in the regulation of the metabolic profile in men. AB - The influence of androgen receptor (AR) GGC repeat polymorphism on the metabolic profile of men has been much less studied than the one of CAG tract polymorphism. Therefore, in this study, we looked for the association of GGC and CAG tract with cardiovascular risk factors in men. Ninety-eight men followed by our andrological unit were retrospectively reviewed. Clinical and biochemical parameters on cardiovascular risk were considered. AR CAG and GGC polymorphisms were studied. GGC triplets were found to be positively and significantly correlated with several cardiovascular risk factors. On the other hand, inverse and significant correlations of CAG triplets were found with insulin and HOMA. As expected, age was positively correlated with cardiovascular risk, whereas total testosterone was inversely correlated with metabolic profile. Estradiol was not found to be correlated with any of the metabolic parameters. In the total sample, multivariate linear regression analysis confirms the positive and independent association of GGC triplets with glycemia, glycated hemoglobin, total cholesterol, triglycerides and homeostasis model assessment of insulin resistance (HOMA), whereas CAG repeat length is negatively associated with insulin and HOMA. Such associations are also substantially confirmed in non-diabetic subjects, whereas in diabetic patients only the GGC tract seems to be involved in the metabolic profile regulation. Our work shows a relevant role for GGC repeat tract in conditioning male cardiovascular risk, thus rendering necessary a deeper analysis on the role of GGC polymorphism both from the molecular and the clinical point of view. PMID- 27251589 TI - DYT-40, a novel synthetic 2-styryl-5-nitroimidazole derivative, blocks malignant glioblastoma growth and invasion by inhibiting AEG-1 and NF-kappaB signaling pathways. AB - Astrocyte elevated gene-1 (AEG-1) has been explored as a novel target for human glioma therapy, thus reflecting its potential contribution to gliomagenesis. In the present study, we investigated the effect of DYT-40, a novel synthetic 2 styryl-5-nitroimidazole derivative, on cell growth and invasion in glioblastoma (GBM) and uncovered the underlying mechanisms of this molecule. DYT-40 induces the intrinsic mitochondrial pathway of apoptosis and inhibits the epithelial mesenchymal transition (EMT) and invasion of GBM cell lines. Furthermore, DYT-40 deactivates PI3K/Akt and MAPK pathways, suppresses AEG-1 expression, and inhibits NF-kappaB nuclear translocation. DYT-40 reduced the tumor volumes in a rat C6 glioma model by apoptotic induction. Moreover, HE staining demonstrated that the glioma rat model treated with DYT-40 exhibited better defined tumor margins and fewer invasive cells to the contralateral striatum compared with the vehicle control and temozolomide-treated rats. Microscopic examination showed a decrease in AEG-1-positive cells in DYT-40-treated rats compared with the untreated controls. DYT-40-treatment increases the in vivo apoptotic response of glioma cells to DYT-40 treatment by TUNEL staining. In conclusion, the inhibitory effects of DYT-40 on growth and invasion in GBM suggest that DYT-40 might be a potential AEG-1 inhibitor to prevent the growth and motility of malignant glioma. PMID- 27251591 TI - Oxidorhenium(V) Complexes with Tetradentate Iminophenolate Ligands: Influence of Ligand Flexibility on the Coordination Motif and Oxygen-Atom-Transfer Activity. AB - The synthesis of oxidorhenium(V) complexes 1-3 coordinated by tetradentate iminophenolate ligands H2L1-H2L3 bearing backbones of different rigidity (alkyl, cycloalkyl, and phenyl bridges) allows for the formation of distinct geometric isomers, including a symmetric trans-oxidochlorido coordination motif in complex 3. The complex employing a cycloalkyl-bridged ligand (2) of intermediate rigidity exhibits an interesting solvent- and temperature-dependent equilibrium between a symmetric (trans) isomer and an asymmetric (cis) isomer in solution. The occurrence of a symmetric isomer for 2 and 3 is confirmed by single-crystal X-ray diffraction analysis. Chlorido abstraction from 2 with AgOTf yields the corresponding cationic complex 2a, which does not exhibit an isomeric equilibrium in solution but adopts the isomeric form predominant for 2 in a given solvent. All complexes were, furthermore, employed in three benchmark oxygen-atom-transfer (OAT) reactions, namely, the reduction of perchlorate, the epoxidation of cyclooctene, and OAT from dimethyl sulfoxide (DMSO) to triphenylphosphane (PPh3), to assess the influence of the isomeric structure on the reactivity in these reactions. In perchlorate reduction, a clear structural influence was observed, where the trans arrangement in 3 led to the complete absence of activity. In the epoxidation reaction, all complexes led to comparable epoxide yields, albeit higher catalytic activity but lower overall stability of the catalysts with a trans arrangement was observed. In OAT from DMSO to PPh3, also a clear structural dependence was observed, where the trans complex 3 led to full phosphane conversion with an excess of oxidant, while the cis compound 1 was completely inactive. PMID- 27251592 TI - Trends in AIDS-related mortality among people aged 60 years and older in Brazil: a nationwide population-based study. AB - The success of antiretroviral therapy has led to an increase in the number of older people living with human immunodeficiency virus worldwide. This study analyzed the epidemiological patterns and time trends of acquired immunodeficiency syndrome (AIDS) related mortality in people aged 60 and older in Brazil from 2000 to 2011. Secondary mortality data from the Brazilian Mortality Information System was used to perform a nationwide population-based study, which included all AIDS-related deaths among people aged 60 years and older in Brazil from 2000 to 2011. Crude and age-adjusted mortality rates (per 100,000 inhabitants) were calculated by sex, age group and place of residence. Trends over time were assessed using joinpoint regression analysis. In the 12-year study period, 12,491,280 deaths were recorded in Brazil, of which 144,175 were AIDS related deaths. A total of 8194 AIDS-related deaths was identified in people aged 60 years and older (0.12% of all deaths and 5.7% of AIDS-related deaths). The overall age-adjusted mortality rate for the period was 4.30 deaths/100,000 inhabitants (95% confidence interval: 3.99-4.64). Males (6.45 deaths/100,000 inhabitants), aged 60-64 years (6.63 deaths/100,000 inhabitants) and residing in the South region (5.94 deaths/100,000 inhabitants) had the highest mortality rates. We observed a significant increase in mortality at the national level and in all the Brazilian regions, with a sharper increase in the most socioeconomically disadvantaged regions of the country, such as the North and Northeast. The findings show that AIDS in older people is an increasing public health problem in Brazil, and reinforce the need to establish public policies for the prevention, early diagnosis and appropriate clinical treatment of this age group. PMID- 27251590 TI - The Global Alliance for Chronic Diseases Supports 15 Major Studies in Hypertension Prevention and Control in Low- and Middle-Income Countries. PMID- 27251593 TI - Vinblastine as a second rescue for the treatment of canine multicentric lymphoma in 39 cases (2005 to 2014). AB - OBJECTIVES: The objective of this study was to retrospectively evaluate response and outcome of dogs with multicentric lymphoma treated with single-agent vinblastine as a second rescue. METHODS: Medical records from 39 client-owned dogs receiving vinblastine rescue treatment (having relapsed on or following completion of UW-Madison and CCNU/L-asparaginase protocols), between 2005 and 2014, were reviewed for information regarding clinical presentation, diagnostic testing, drug dosage, number of treatments, side effects, response and outcome. RESULTS: The median starting dose of vinblastine was 2.6 mg/m(2) (1.7 to 2.8 mg/m(2) ), administered weekly until disease progression. Of the 39 dogs treated, 3 dogs (7.7%) achieved a complete remission, 7 dogs (17.9%) achieved a partial response, 18 dogs (46.2%) maintained stable disease and 11 (28.2%) had progressive disease. Ten dogs (25.6%) developed a grade III or IV neutropenia, and 4 dogs (10.3%) developed grade III or IV thrombocytopenia (one dog in both categories). After starting vinblastine, the median progression-free survival was 29.5 days (0 to 77 days) and overall median survival time was 46 days (4 to 250 days). Duration of first remission was identified as a positive predictor of outcome. CLINICAL SIGNIFICANCE: Single-agent vinblastine is well tolerated in dogs with relapsed or refractory lymphoma. Responses were incomplete and short lasting. PMID- 27251594 TI - Knockdown of asparagine synthetase (ASNS) suppresses cell proliferation and inhibits tumor growth in gastric cancer cells. AB - OBJECTIVE: Asparagine synthetase (ASNS) gene encodes an enzyme that catalyzes the glutamine- and ATP-dependent conversion of aspartic acid to asparagine. ASNS is deemed as a promising therapeutic target and its expression is associated with the chemotherapy resistance in several human cancers. However, its role in gastric cancer tumorigenesis has not been investigated. METHODS: In this study, we employed small interfering RNA (siRNA) to transiently knockdown ASNS in two gastric cancer cell lines, AGS and MKN-45, followed by growth rate assay and colony formation assay. Dose response curve analysis was performed in AGS and MKN 45 cells with stable ASNS knockdown to assess sensitivity to cisplatin. Xenograft experiment was performed to examine in vivo synergistic effects of ASNS depletion and cisplatin on tumor growth. Expression level of ASNS was evaluated in human patient samples using quantitative PCR. Kaplan-Meier curve analysis was performed to evaluate association between ASNS expression and patient survival. RESULTS: Transient knockdown of ASNS inhibited cell proliferation and colony formation in AGS and MKN-45 cells. Stable knockdown of ASNS conferred sensitivity to cisplatin in these cells. Depletion of ASNS and cisplatin treatment exerted synergistic effects on tumor growth in AGS xenografts. Moreover, ASNS was found to be up regulated in human gastric cancer tissues compared with matched normal colon tissues. Low expression of ASNS was significantly associated with better survival in gastric cancer patients. CONCLUSION: ASNS may contribute to gastric cancer tumorigenesis and may represent a novel therapeutic target for prevention or intervention of gastric cancer. PMID- 27251596 TI - Truth is elusive. PMID- 27251595 TI - Synthesis and regioselective functionalization of perhalogenated BODIPYs. AB - Three perhalogenated BODIPYs (1b-3b), bearing chloro and bromo groups at all carbon positions, were synthesized and characterized. The reactivity of BODIPY 3b was investigated under Stille cross-coupling reactions, and single crystal X-ray analysis was used to confirm the regioselectivity of the reactions. Further substitution at the boron atom produced nona-functionalized BODIPYs 7a,b, which show 676 and 739 nm emissions with 91 and 100 nm Stokes shifts, respectively. PMID- 27251597 TI - Pharmacological treatment versus acute lung injury/acute respiratory distress syndrome - reflections from the clinical perspective and yacht racing (and more). PMID- 27251598 TI - Behavioral Pain Scale - translation, reliability, and validity in a Swedish context. AB - BACKGROUND: Assessing pain in the intensive care unit (ICU) is challenging. Due to intubation and sedation, communication can be limited. International guidelines recommend assessing pain with instruments based on behavioral parameters when critically ill patients are unable to self-report their pain level. One of the recommended instruments, the Behavioral Pain Scale (BPS), has shown good validity and reliability in international studies. The aim of this study was to translate and adapt the BPS for critically ill intubated and non intubated patients in a Swedish ICU context and to assess inter-rater reliability and discriminant validity. METHODS: The BPS (both for intubated and non-intubated patients) was translated and adapted into Swedish using a translation method consisting of ten steps. The Swedish version was then tested for inter-rater reliability and discriminant validity on 20 critically ill patients (10 intubated and 10 non-intubated) before and directly after a potentially painful procedure (repositioning). RESULTS: The Swedish version of the BPS showed inter-rater reliability with a percentage agreement of 85% when tested on a sample of critically ill patients. The instrument also showed discriminant validity between assessments at rest and after repositioning. CONCLUSION: Results of the Swedish version of the BPS support its use in critically ill patients who cannot self report their pain level. Still, additional studies are needed to further explore its reliability and validity in the Swedish ICU context. PMID- 27251599 TI - Photophysical properties of pyrrolocytosine, a cytosine fluorescent base analogue. AB - The photophysical behavior of pyrrolocytosine (PC), a fluorescent base analogue of cytosine, has been investigated using theoretical approaches. The similarities between the PC and cytosine structures allow PC to maintain the pseudo-Watson Crick base-pairing arrangement with guanine. Cytosine, similar to the other natural nucleobases, is practically non-fluorescent, because of ultrafast radiationless decay occurring through conical intersections. PC displays a much higher fluorescence quantum yield than cytosine, making it an effective fluorescent marker to study the structure, function, and dynamics of DNA/RNA complexes. Similar to 2-aminopurine, a constitutional isomer of adenine that base pairs with thymine, PC's fluorescence is quenched when it is incorporated into a dinucleotide or a trinucleotide. In this work we examine the photophysical properties of isolated PC, microhydrated PC, as well as, complexes where PC is either base-stacked or hydrogen-bonded with guanine. Our results indicate that hydration affects the radiationless decay pathways in PC by destabilizing conical intersections. The calculations of dimers and trimers show that the radiative decay is affected by pi stacking, while the presence of charge transfer states between PC and guanine may contribute to radiationless decay. PMID- 27251600 TI - N-Heterocyclic olefins as efficient phase-transfer catalysts for base-promoted alkylation reactions. AB - N-Heterocyclic olefins (NHOs) have very recently emerged as efficient promoters for several chemical reactions due to their strong Bronsted/Lewis basicities. Here we report the novel application of NHOs as efficient phase-transfer organocatalysts for synthetically important alkylation reactions on a wide range of substrates, further demonstrating the great potential of NHOs in organic chemistry. PMID- 27251601 TI - Management of a patient with pericardial decompression syndrome and HOCM. AB - A 44-year-old man, with a history of arterial hypertension, was referred with increasing shortness of breath due to a large pericardial effusion and imminent tamponade. Emergency ultrasound-guided pericardiocentesis resulted in the rapid withdrawal of 2760 cc of serous fluid. 3 hours later, the patient developed acute pulmonary oedema, which was successfully treated. Hypertrophic obstructive cardiomyopathy was later diagnosed and malignancy was excluded as a cause of the effusion. Clinicians performing pericardiocentesis need to be aware of pericardial decompression syndrome (PDS), a rare but serious complication. Although the underlying mechanisms causing PDS are not fully understood, patients with high left ventricular (LV) filling pressures are at particular risk. In other words: diastolic dysfunction of the LV is a risk factor for the occurrence of PDS. PMID- 27251602 TI - 5-Fluorouracil-induced acute reversible heart failure not explained by coronary spasms, myocarditis or takotsubo: lessons from MRI. AB - A 69-year-old woman presented with arterial hypotension, pulmonary oedema and a severely depressed left ventricular ejection fraction (LVEF) of 25% only 3 days after having received her first treatment for colorectal cancer with 5 fluorouracil (5-FU)-based therapy. The ECG demonstrated widespread ST-segment depression and echocardiography showed uniform hypokinesia of all left ventricular (LV) myocardial segments without signs of regional LV ballooning. Coronary angiography was normal and the patient gained full recovery after receiving treatment with heart failure medication. Interestingly, cardiac MRI scan 9 days later showed a normal LVEF with signs of neither myocardial oedema nor necrosis. Despite the high therapeutic efficacy of 5-FU in treatment of colorectal cancer, it is associated with undesired cardiac toxicities including coronary spasms, toxic inflammation and takotsubo cardiomyopathy. However, our patient did not fulfil the diagnostic criteria for the aforementioned complications. Based on this case report, we discuss alternative mechanisms including myocardial adenosine triphosphate depletion suggested from animal experiments. PMID- 27251603 TI - Intracardiac metastasis of high-grade sarcoma of the neck causing right ventricular outflow obstruction. PMID- 27251604 TI - Spleen and gone? An interesting case of fever in a young man. PMID- 27251605 TI - Functional analysis of thioredoxin from the desert lichen-forming fungus, Endocarpon pusillum Hedwig, reveals its role in stress tolerance. AB - Endocarpon pusillum is a lichen-forming fungus with an outstanding stress resistance property closely related to its antioxidant system. In this study, thioredoxin (Trx), one of the main components of antioxidant defense systems in E. pusillum (EpTrx), was characterized and analyzed both in transgenic yeasts and in vitro. Our analyses identified that the heterologous expression of EpTrx in the yeast Pichia pastoris significantly enhanced its resistance to osmotic and oxidative stresses. Assays in vitro showed EpTrx acted as a disulfide reductase as well as a molecular chaperone by assembling into various polymeric structures. Upon exposure to heat-shock stress, EpTrx exhibited weaker disulfide reductase activity but stronger chaperone activity, which coincided with the switching of the protein complexes from low molecular weight forms to high molecular weight complexes. Specifically, we found that Cys31 near but not at the active site was crucial in promoting the structural and functional transitions, most likely by accelerating the formation of intermolecular disulfide bond. Transgenic Saccharomyces cerevisiae harboring the native EpTrx exhibited stronger tolerance to oxidative, osmotic and high temperature stresses than the corresponding yeast strain containing the mutant EpTrx (C31S). Our results provide the first molecular evidence on how Trx influences stress response in lichen-forming fungi. PMID- 27251606 TI - The cross-talk between enterocytes and intraepithelial lymphocytes. AB - The gut mucosa is continuously exposed to food and microbial antigens. Both enterocytes and intraepithelial lymphocytes have a pivotal role in maintaining the integrity of intestinal mucosa, as these cells guarantee a first line of defense against pathogens and toxic molecules. Enterocytes maintain a physical barrier against microbes and directly contribute to the gut homeostasis by sampling the luminal agents through several pattern recognition receptors or presenting antigen to mucosa T cells. Similarly, due to a close physical contact with the intestinal epithelial cells, the intraepithelial lymphocytes represent an important part of the gut lymphoid tissue, contrasting the entry and spread of pathogens. An alteration of the cross-talk between intestinal epithelial cells and intraepithelial lymphocytes might actively contribute to the development of intestinal immune disorders, as occurring in patients with celiac disease. In genetically predisposed individuals, the gluten exposure results in a massive production of interleukin-15, activation of intraepithelial lymphocytes, and modification of small intestinal mucosa architecture and function. We will review the recent studies on the pathophysiology of cross-talk between enterocytes and intraepithelial T cells, and how this interaction is crucial for intestinal integrity and homeostasis. PMID- 27251607 TI - Mechanism of human rhinovirus infections. AB - About 150 human rhinovirus serotypes are responsible for more than 50 % of recurrent upper respiratory infections. Despite having similar 3D structures, some bind members of the low-density lipoprotein receptor family, some ICAM-1, and some use CDHR3 for host cell infection. This is also reflected in the pathways exploited for cellular entry. We found that even rhinovirus serotypes binding the same receptor can travel along different endocytic pathways and release their RNA genome into the cytosol at different locations. How this may account for distinct immune responses elicited by various rhinoviruses and the observed symptoms of the common cold is briefly discussed. PMID- 27251608 TI - Study on the mechanisms of the bronchodilator effects of Folium Eriobotryae and the selected active ingredient on isolated guinea pig tracheal strips. AB - CONTEXT: Folium Eriobotryae (FE), the dry leaf of Eriobotrya japonica (Thunb.) Lindl. (Rosaceae), has been widely used to treat respiratory disorders. OBJECTIVE: To examine the bronchodilatory activity of FE and the potential mechanisms involved. MATERIALS AND METHODS: The effects of ethyl acetate fraction of FE (EFE) (0.05-0.3 mg/mL) on the isolated tracheal strips, and ursolic acid (UA) (5-30 MUg/mL) that was the main constituent of EFE, were tested in vitro. Meanwhile, acetylcholine (Ach) and histamine (His)-induced bronchospasm were conducted in vivo in guinea pig. Furthermore, mechanisms of relaxant effects of EFE and UA were evaluated in the absence and presence of specific inhibitors. RESULTS: With in vitro studies, the contractile response evoked by Ach or His (EC50 = 0.21 and 0.16 mg/mL) was decreased by EFE, and UA caused a concentration dependent relaxation precontracted by His (EC50 = 23.2 MUg/mL). With in vivo studies, EFE strongly prolonged preconvulsive time similar to isoprenalin. The bronchodilator effects of EFE could be blocked by propranolol (1 MUM), NG-nitro-l arginine methyl ester (l-NAME) (100 MUM) and 1H-[1,2,4]oxadiazolo[4,3 a]quinoxaline-1-one (ODQ) (1 MUM). EFE also inhibited the contraction in Ca2+ free medium and produced rightward parallel displacement of CaCl2 curves. In addition, the relaxant effects of UA could only be blocked by l-NAME and ODQ. DISCUSSION AND CONCLUSION: These results suggest that bronchodilator activities of EFE were related to activation of beta-adrenoceptor and NO/cGMP pathway. Blockage of Ca2+ channels and inhibition of IP3R-mediated internal Ca2+ release were also involved. Additionally, UA produced relaxant effects by the NO/cGMP pathway. PMID- 27251609 TI - Stigma, Social Structure, and the Biomedical Framework: Exploring the Stigma Experiences of Inpatient Service Users in Two Belgian Psychiatric Hospitals. AB - The study discusses the stigma experiences of service users in mental health care, within the debate on the role of the biomedical framework for mental health care and power relations in society. Interview data of inpatient users ( n = 42) and care providers ( n = 43) from two Belgian psychiatric hospitals were analyzed using a constructivist grounded theory approach: Findings offer insight into how stigma experiences are affected by social structure. Stigma seemed to be related to the relation between care providers and service users their social position. The concept "mental health literacy" is used to frame this finding. In paying attention to the specific cultural and normative context, which influences the relationship between mental health literacy and stigma, it is further possible to cast some light on the meaning of the biomedical model for the construction and maintenance of power relations in mental health care and broader society. PMID- 27251611 TI - Changes to the Review Process. PMID- 27251610 TI - Short-term treatment outcomes in human immunodeficiency virus type-1 and hepatitis B virus co-infections. AB - BACKGROUND: Co-infection of HIV with HBV is common in West Africa but little information is available on the effects of HBV on short-term therapy for HIV patients. A 28 day longitudinal study was conducted to examine short-term antiretroviral therapy (ART) outcomes in HIV infected individuals with HBV co infection. METHODS: Plasma from 18 HIV infected individuals co-infected with HBV and matched controls with only HIV infection were obtained at initiation, and 7 and 28 days after ART. HIV-1 viral load changes were monitored. Clinical and demographic data were also obtained from patient folders, and HIV-1 drug resistance mutation and subtype analysis performed. RESULTS: The presence of HBV co-infection did not significantly affect HIV-1 viral load changes within 7 or 28 days. The CD4(+) counts on the other hand of patients significantly affected the magnitude of HIV-1 viral load decline after 7 days (rho = -0.441, p = 0.040), while the pre-ART HIV-1 VL (rho = 0.844, p = <0.001) and sex (U = 19.0, p = 0.020) also determined HIV-1 viral load outcomes after 28 days of ART. Even though the geometric sensitivity score of HIV-1 strains were influenced by the HIV-1 subtypes (U = 56.00; p = 0.036), it was not a confounder for ART outcomes. CONCLUSIONS: There may be the need to consider the confounder effects of sex, pre ART CD4(+), and pre-ART HIV-1 viral load in the discourse on HIV and HBV co infection. PMID- 27251612 TI - Neural Evidence for a Role of Urgency in the Speed-Accuracy Trade-off in Perceptual Decision-Making. PMID- 27251613 TI - How Do Microtubule Dynamics Relate to the Hallmarks of Learning and Memory? PMID- 27251614 TI - Visual Deprivation During the Critical Period Enhances Layer 2/3 GABAergic Inhibition in Mouse V1. AB - The role of GABAergic signaling in establishing a critical period for experience in visual cortex is well understood. However, the effects of early experience on GABAergic synapses themselves are less clear. Here, we show that monocular deprivation (MD) during the adolescent critical period produces marked enhancement of GABAergic signaling in layer 2/3 of mouse monocular visual cortex. This enhancement coincides with a weakening of glutamatergic inputs, resulting in a significant reduction in the ratio of excitation to inhibition. The potentiation of GABAergic transmission arises from both an increased number of inhibitory synapses and an enhancement of presynaptic GABA release from parvalbumin- and somatostatin-expressing interneurons. Our results suggest that augmented GABAergic inhibition contributes to the experience-dependent regulation of visual function. SIGNIFICANCE STATEMENT: Visual experience shapes the synaptic organization of cortical circuits in the mouse brain. Here, we show that monocular visual deprivation enhances GABAergic synaptic inhibition in primary visual cortex. This enhancement is mediated by an increase in both the number of postsynaptic GABAergic synapses and the probability of presynaptic GABA release. Our results suggest a contributing mechanism to altered visual responses after deprivation. PMID- 27251615 TI - Transient P2X7 Receptor Antagonism Produces Lasting Reductions in Spontaneous Seizures and Gliosis in Experimental Temporal Lobe Epilepsy. AB - Neuroinflammation is thought to contribute to the pathogenesis and maintenance of temporal lobe epilepsy, but the underlying cell and molecular mechanisms are not fully understood. The P2X7 receptor is an ionotropic receptor predominantly expressed on the surface of microglia, although neuronal expression has also been reported. The receptor is activated by the release of ATP from intracellular sources that occurs during neurodegeneration, leading to microglial activation and inflammasome-mediated interleukin 1beta release that contributes to neuroinflammation. Using a reporter mouse in which green fluorescent protein is induced in response to the transcription of P2rx7, we show that expression of the receptor is selectively increased in CA1 pyramidal and dentate granule neurons, as well as in microglia in mice that developed epilepsy after intra-amygdala kainic acid-induced status epilepticus. P2X7 receptor levels were increased in hippocampal subfields in the mice and in resected hippocampus from patients with pharmacoresistant temporal lobe epilepsy. Cells transcribing P2rx7 in hippocampal slices from epileptic mice displayed enhanced agonist-evoked P2X7 receptor currents, and synaptosomes from these animals showed increased P2X7 receptor levels and altered calcium responses. A 5 d treatment of epileptic mice with systemic injections of the centrally available, potent, and specific P2X7 receptor antagonist JNJ-47965567 (30 mg/kg) significantly reduced spontaneous seizures during continuous video-EEG monitoring that persisted beyond the time of drug presence in the brain. Hippocampal sections from JNJ-47965567-treated animals obtained >5 d after treatment ceased displayed strongly reduced microgliosis and astrogliosis. The present study suggests that targeting the P2X7 receptor has anticonvulsant and possibly disease-modifying effects in experimental epilepsy. SIGNIFICANCE STATEMENT: Temporal lobe epilepsy is the most common and drug-resistant form of epilepsy in adults. Neuroinflammation is implicated as a pathomechanism, but the upstream mechanisms driving gliosis and how important this is for seizures remain unclear. In our study, we show that the ATP-gated P2X7 receptor is upregulated in experimental epilepsy and resected hippocampus from epilepsy patients. Targeting the receptor with a new centrally available antagonist, JNJ-47965567, suppressed epileptic seizures well beyond the time of treatment and reduced underlying gliosis in the hippocampus. The findings suggest a potential disease-modifying treatment for epilepsy based on targeting the P2X7 receptor. PMID- 27251616 TI - Compartment-Specific Regulation of Autophagy in Primary Neurons. AB - Autophagy is an essential degradative pathway that maintains neuronal homeostasis and prevents axon degeneration. Initial observations suggest that autophagy is spatially regulated in neurons, but how autophagy is regulated in distinct neuronal compartments is unclear. Using live-cell imaging in mouse hippocampal neurons, we establish the compartment-specific mechanisms of constitutive autophagy under basal conditions, as well as in response to stress induced by nutrient deprivation. We find that at steady state, the cell soma contains populations of autophagosomes derived from distinct neuronal compartments and defined by differences in maturation state and dynamics. Axonal autophagosomes enter the soma and remain confined within the somatodendritic domain. This compartmentalization likely facilitates cargo degradation by enabling fusion with proteolytically active lysosomes enriched in the soma. In contrast, autophagosomes generated within the soma are less mobile and tend to cluster. Surprisingly, starvation did not induce autophagy in either the axonal or somatodendritic compartment. While starvation robustly decreased mTORC1 signaling in neurons, this decrease was not sufficient to activate autophagy. Furthermore, pharmacological inhibition of mammalian target of rapamycin with Torin1 also was not sufficient to markedly upregulate neuronal autophagy. These observations suggest that the primary physiological function of autophagy in neurons may not be to mobilize amino acids and other biosynthetic building blocks in response to starvation, in contrast to findings in other cell types. Rather, constitutive autophagy in neurons may function to maintain cellular homeostasis by balancing synthesis and degradation, especially within distal axonal processes far removed from the soma. SIGNIFICANCE STATEMENT: Autophagy is an essential homeostatic process in neurons, but neuron-specific mechanisms are poorly understood. Here, we compare autophagosome dynamics within neuronal compartments. Axonal autophagy is a vectorial process that delivers cargo from the distal axon to the soma. The soma, however, contains autophagosomes at different maturation states, including input received from the axon combined with locally generated autophagosomes. Once in the soma, autophagosomes are confined to the somatodendritic domain, facilitating cargo degradation and recycling of biosynthetic building blocks to primary sites of protein synthesis. Neuronal autophagy is not robustly upregulated in response to starvation or mammalian target of rapamycin inhibition, suggesting that constitutive autophagy in neurons maintains homeostasis by playing an integral role in regulating the quality of the neuronal proteome. PMID- 27251617 TI - Neural Representation of Odor-Guided Behavior in the Rat Olfactory Thalamus. AB - The mediodorsal thalamus (MDT) is a higher-order corticocortical thalamic nucleus involved in cognition and memory. However, anatomically, the MDT is also the primary site of olfactory representation in the thalamus, receiving strong inputs from olfactory cortex and having reciprocal connections with orbitofrontal cortex (OFC). Nonetheless, its role in olfaction remains unclear. Here, we recorded single units in the MDT, as well as local field potentials in the MDT, piriform cortex (PCX), and OFC in rats performing a two-alternative odor discrimination task. We show that subsets of MDT units display odorant selectivity during sampling, as well as encoding of spatio-motor aspects of the task. Furthermore, the olfactory trans-thalamic network rapidly switches functional connectivity between MDT and cortical areas depending on current task demands, with, for example, MDT-PCX coupling enhanced during odor sampling and MDT-OFC coupling enhanced during the decision/goal approach compared with baseline and presampling. These results demonstrate MDT representation of diverse sensorimotor components of an olfactory task. SIGNIFICANCE STATEMENT: The mediodorsal thalamus (MDT) is the major olfactory thalamic nucleus and links the olfactory archicortex with the prefrontal neocortex. The MDT is well known to be involved in higher order cognitive and memory functions, but its role in olfaction is poorly understood. Here, using single-unit and local field potential analyses, we explored MDT function during an odor-guided decision task in rats. We describe MDT odor and multisensory coding and demonstrate behavior-dependent functional connectivity within the MDT/sensory cortex/prefrontal cortex network. Our results suggest a rich representation of olfactory and other information within MDT required to perform this odor-guided task. Our work opens a new model system for understanding MDT function and exploring the important role of MDT in cortical cortical communication. PMID- 27251618 TI - An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons. AB - To investigate excitatory and inhibitory GABA actions in cortical neuronal networks, we present a novel optogenetic approach using a mouse knock-in line with conditional expression of channelrhodopsin-2 (ChR2) in GABAergic interneurons. During whole-cell recordings from hippocampal and neocortical slices from postnatal day (P) 2-P15 mice, photostimulation caused depolarization and excitation of interneurons and evoked barrages of postsynaptic GABAergic currents. Excitatory/inhibitory GABA actions on pyramidal cells were assessed by monitoring the alteration in the frequency of EPSCs during photostimulation of interneurons. We found that in slices from P2-P8 mice, photostimulation evoked an increase in EPSC frequency, whereas in P9-P15 mice the response switched to a reduction in EPSC frequency, indicating a developmental excitatory-to-inhibitory switch in GABA actions on glutamatergic neurons. Using a similar approach in urethane-anesthetized animals in vivo, we found that photostimulation of interneurons reduces EPSC frequency at ages P3-P9. Thus, expression of ChR2 in GABAergic interneurons of mice enables selective photostimulation of interneurons during the early postnatal period, and these mice display a developmental excitatory-to-inhibitory switch in GABA action in cortical slices in vitro, but so far show mainly inhibitory GABA actions on spontaneous EPSCs in the immature hippocampus and neocortex in vivo SIGNIFICANCE STATEMENT: We report a novel optogenetic approach for investigating excitatory and inhibitory GABA actions in mice with conditional expression of channelrhodopsin-2 in GABAergic interneurons. This approach shows a developmental excitatory-to-inhibitory switch in the actions of GABA on glutamatergic neurons in neocortical and hippocampal slices from neonatal mouse pups in vitro, but also reveals inhibitory GABA actions in the neonatal mouse neocortex and hippocampus in vivo. PMID- 27251619 TI - Representation of Behavioral Tactics and Tactics-Action Transformation in the Primate Medial Prefrontal Cortex. AB - To expedite the selection of action under a structured behavioral context, we develop an expedient to promote its efficiency: tactics for action selection. Setting up a behavioral condition for subhuman primates (Macaca fuscata) that induced the development of a behavioral tactics, we explored neuronal representation of tactics in the medial frontal cortex. Here we show that neurons in the posterior medial prefrontal cortex, but not much in the medial premotor cortex, exhibit activity representing the behavioral tactics, in advance of action-selective activity. Such activity appeared during behavioral epochs of its retrieval from instruction cues, maintenance in short-term memory, and its implementation for the achievement of action selection. At a population level, posterior medial prefrontal cortex neurons take part in transforming the tactics information into the information representing action selection. The tactics representation revealed an aspect of neural mechanisms for an adaptive behavioral control, taking place in the medial prefrontal cortex. SIGNIFICANCE STATEMENT: We studied behavioral significance of neuronal activity in the posterior medial prefrontal cortex (pmPFC) and found the representation of behavioral tactics defined as specific and efficient ways to achieve objectives of actions. Neuronal activity appeared during behavioral epochs of its retrieval from instruction cues, maintenance in short-term memory, and its use preceding the achievement of action selection. We found further that pmPFC neurons take part in transforming the tactics information into the information representing action selection. A majority of individual neurons was recruited during a limited period in each behavioral epoch, constituting, as a whole, a temporal cascade of activity. Such dynamics found in behavioral-tactics specific activity characterize the participation of pmPFC neurons in executive control of purposeful behavior. PMID- 27251621 TI - Sentential Negation Might Share Neurophysiological Mechanisms with Action Inhibition. Evidence from Frontal Theta Rhythm. AB - According to the literature, negations such as "not" or "don't" reduce the accessibility in memory of the concepts under their scope. Moreover, negations applied to action contents (e.g., "don't write the letter") impede the activation of motor processes in the brain, inducing "disembodied" representations. These facts provide important information on the behavioral and neural consequences of negations. However, how negations themselves are processed in the brain is still poorly understood. In two electrophysiological experiments, we explored whether sentential negation shares neural mechanisms with action monitoring or inhibition. Human participants read action-related sentences in affirmative or negative form ("now you will cut the bread" vs "now you will not cut the bread") while performing a simultaneous Go/NoGo task. The analysis of the EEG rhythms revealed that theta oscillations were significantly reduced for NoGo trials in the context of negative sentences compared with affirmative sentences. Given the fact that theta oscillations are often considered as neural markers of response inhibition processes, their modulation by negative sentences strongly suggests that negation uses neural resources of response inhibition. We propose a new approach that views the syntactic operator of negation as relying on the neural machinery of high-order action-monitoring processes. SIGNIFICANCE STATEMENT: Previous studies have shown that linguistic negation reduces the accessibility of the negated concepts and suppresses the activation of specific brain regions that operate in affirmative statements. Although these studies focus on the consequences of negation on cognitive and neural processes, the proper neural mechanisms of negation have not yet been explored. In the present EEG study, we tested the hypothesis that negation uses the neural network of action inhibition. Using a Go/NoGo task embedded in a sentence comprehension task, we found that negation in the context of NoGo trials modulates frontal theta rhythm, which is usually considered a signature of action inhibition and control mechanisms. PMID- 27251620 TI - Decreasing Striatopallidal Pathway Function Enhances Motivation by Energizing the Initiation of Goal-Directed Action. AB - Altered dopamine D2 receptor (D2R) binding in the striatum has been associated with abnormal motivation in neuropsychiatric disorders, including schizophrenia. Here, we tested whether motivational deficits observed in mice with upregulated D2Rs (D2R-OEdev mice) are reversed by decreasing function of the striatopallidal "no-go" pathway. To this end, we expressed the Galphai-coupled designer receptor hM4D in adult striatopallidal neurons and activated the receptor with clozapine-N oxide (CNO). Using a head-mounted miniature microscope we confirmed with calcium imaging in awake mice that hM4D activation by CNO inhibits striatopallidal function measured as disinhibited downstream activity in the globus pallidus. Mice were then tested in three operant tasks that address motivated behavior, the progressive ratio task, the progressive hold-down task, and outcome devaluation. Decreasing striatopallidal function in the dorsomedial striatum or nucleus accumbens core enhanced motivation in D2R-OEdev mice and control littermates. This effect was due to increased response initiation but came at the cost of goal directed efficiency. Moreover, response vigor and the sensitivity to changes in reward value were not altered. Chronic activation of hM4D by administering CNO for 2 weeks in drinking water did not affect motivation due to a tolerance effect. However, the acute effect of CNO on motivation was reinstated after discontinuing chronic treatment for 48 h. Used as a therapeutic approach, striatopallidal inhibition should consider the risk of impairing goal-directed efficiency and behavioral desensitization. SIGNIFICANCE STATEMENT: Motivation involves a directional component that allows subjects to efficiently select the behavior that will lead to an optimal outcome and an activational component that initiates and maintains the vigor and persistence of actions. Striatal output pathways modulate motivated behavior, but it remains unknown how these pathways regulate specific components of motivation. Here, we found that the indirect pathway controls response initiation without affecting response vigor or the sensitivity to changes in the reward outcome. A specific enhancement in the activational component of motivation, however, can come at the cost of goal directed efficiency when a sustained response is required to obtain the goal. These data should inform treatment strategies for brain disorders with impaired motivation such as schizophrenia and Parkinson's disease. PMID- 27251622 TI - Cue-Evoked Dopamine Release Rapidly Modulates D2 Neurons in the Nucleus Accumbens During Motivated Behavior. AB - Dopaminergic neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) fire in response to unpredicted rewards or to cues that predict reward delivery. Although it is well established that reward-related events elicit dopamine release in the NAc, the role of rapid dopamine signaling in modulating NAc neurons that respond to these events remains unclear. Here, we examined dopamine's actions in the NAc in the rat brain during an intracranial self-stimulation task in which a cue predicted lever availability for electrical stimulation of the VTA. To distinguish actions of dopamine at select receptors on NAc neurons during the task, we used a multimodal sensor that probes three aspects of neuronal communication simultaneously: neurotransmitter release, cell firing, and identification of dopamine receptor type. Consistent with prior studies, we first show dopamine release events in the NAc both at cue presentation and after lever press (LP). Distinct populations of NAc neurons encode these behavioral events at these same locations selectively. Using our multimodal sensor, we found that dopamine-mediated responses after the cue involve exclusively a subset of D2-like receptors (D2Rs), whereas dopamine mediated responses proximal to the LP are mediated by both D1-like receptors (D1R) and D2Rs. These results demonstrate for the first time that dopamine mediated responses after cues that predict reward availability are specifically linked to its actions at a subset of neurons in the NAc containing D2Rs. SIGNIFICANCE STATEMENT: Successful reward procurement typically involves the completion of a goal-directed behavior in response to appropriate environmental cues. Although numerous studies link the mesolimbic dopamine system with these processes, how dopamine's effects are mediated on the receptor level within a key neural substrate, the nucleus accumbens, remains elusive. Here, we used a unique multimodal sensor that reveals three aspects of neuronal interactions: neurotransmitter release, cell firing, and dopamine-receptor type. We identified a key role of D2-like receptor (D2R)-expressing neurons in response to a reward predicting cue, whereas both the D2R and D1R types modulate responses of neurons proximal to the goal-directed action. This work provides novel insight into the unique role of D2R-mediated neuronal activity to reward-associated cues, a fundamental aspect of motivated behaviors. PMID- 27251623 TI - Dopamine Release in the Nonhuman Primate Caudate and Putamen Depends upon Site of Stimulation in the Subthalamic Nucleus. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory Parkinson's disease. Although DBS has recognized clinical utility, its biologic mechanisms are not fully understood, and whether dopamine release is a potential factor in those mechanisms is in dispute. We tested the hypothesis that STN DBS-evoked dopamine release depends on the precise location of the stimulation site in the STN and the site of recording in the caudate and putamen. We conducted DBS with miniature, scaled-to-animal size, multicontact electrodes and used functional magnetic resonance imaging to identify the best dopamine recording site in the brains of nonhuman primates (rhesus macaques), which are highly representative of human brain anatomy and circuitry. Real-time stimulation-evoked dopamine release was monitored using in vivo fast-scan cyclic voltammetry. This study demonstrates that STN DBS-evoked dopamine release can be reduced or increased by redirecting STN stimulation to a slightly different site. SIGNIFICANCE STATEMENT: Electrical stimulation of deep structures of the brain, or deep brain stimulation (DBS), is used to modulate pathological brain activity. However, technological limitations and incomplete understanding of the therapeutic mechanisms of DBS prevent personalization of this therapy and may contribute to less-than-optimal outcomes. We have demonstrated that DBS coincides with changes in dopamine neurotransmitter release in the basal ganglia. Here we mapped relationships between DBS and changes in neurochemical activity. Importantly, this study shows that DBS-evoked dopamine release can be reduced or increased by refocusing the DBS on a slightly different stimulation site. PMID- 27251624 TI - Broadband Electrophysiological Dynamics Contribute to Global Resting-State fMRI Signal. AB - Spontaneous activity observed with resting-state fMRI is used widely to uncover the brain's intrinsic functional networks in health and disease. Although many networks appear modular and specific, global and nonspecific fMRI fluctuations also exist and both pose a challenge and present an opportunity for characterizing and understanding brain networks. Here, we used a multimodal approach to investigate the neural correlates to the global fMRI signal in the resting state. Like fMRI, resting-state power fluctuations of broadband and arrhythmic, or scale-free, macaque electrocorticography and human magnetoencephalography activity were correlated globally. The power fluctuations of scale-free human electroencephalography (EEG) were coupled with the global component of simultaneously acquired resting-state fMRI, with the global hemodynamic change lagging the broadband spectral change of EEG by ~5 s. The levels of global and nonspecific fluctuation and synchronization in scale-free population activity also varied across and depended on arousal states. Together, these results suggest that the neural origin of global resting-state fMRI activity is the broadband power fluctuation in scale-free population activity observable with macroscopic electrical or magnetic recordings. Moreover, the global fluctuation in neurophysiological and hemodynamic activity is likely modulated through diffuse neuromodulation pathways that govern arousal states and vigilance levels. SIGNIFICANCE STATEMENT: This study provides new insights into the neural origin of resting-state fMRI. Results demonstrate that the broadband power fluctuation of scale-free electrophysiology is globally synchronized and directly coupled with the global component of spontaneous fMRI signals, in contrast to modularly synchronized fluctuations in oscillatory neural activity. These findings lead to a new hypothesis that scale-free and oscillatory neural processes account for global and modular patterns of functional connectivity observed with resting-state fMRI, respectively. PMID- 27251626 TI - DNA Methyltransferase 1 Is Indispensable for Development of the Hippocampal Dentate Gyrus. AB - Development of the hippocampal dentate gyrus (DG) in the mammalian brain is achieved through multiple processes during late embryonic and postnatal stages, with each developmental step being strictly governed by extracellular cues and intracellular mechanisms. Here, we show that the maintenance DNA methyltransferase 1 (Dnmt1) is critical for development of the DG in the mouse. Deletion of Dnmt1 in neural stem cells (NSCs) at the beginning of DG development led to a smaller size of the granule cell layer in the DG. NSCs lacking Dnmt1 failed to establish proper radial processes or to migrate into the subgranular zone, resulting in aberrant neuronal production in the molecular layer of the DG and a reduction of integrated neurons in the granule cell layer. Interestingly, prenatal deletion of Dnmt1 in NSCs affected not only the developmental progression of the DG but also the properties of NSCs maintained into adulthood: Dnmt1-deficient NSCs displayed impaired neurogenic ability and proliferation. We also found that Dnmt1 deficiency in NSCs decreased the expression of Reelin signaling components in the developing DG and increased that of the cell cycle inhibitors p21 and p57 in the adult DG. Together, these findings led us to propose that Dnmt1 functions as a key regulator to ensure the proper development of the DG, as well as the proper status of NSCs maintained into adulthood, by modulating extracellular signaling and intracellular mechanisms. SIGNIFICANCE STATEMENT: Here, we provide evidence that Dnmt1 is required for the proper development of the hippocampal dentate gyrus (DG). Deletion of Dnmt1 in neural stem cells (NSCs) at an early stage of DG development impaired the ability of NSCs to establish secondary radial glial scaffolds and to migrate into the subgranular zone of the DG, leading to aberrant neuronal production in the molecular layer, increased cell death, and decreased granule neuron production. Prenatal deletion of Dnmt1 in NSCs also induced defects in the proliferation and neurogenic ability of adult NSCs. Furthermore, we found that Dnmt1 regulates the expression of key extracellular signaling components during developmental stages while modulating intracellular mechanisms for proliferation and neuronal production of NSCs in the adult. PMID- 27251627 TI - Reconstructing Perceived and Retrieved Faces from Activity Patterns in Lateral Parietal Cortex. AB - Recent findings suggest that the contents of memory encoding and retrieval can be decoded from the angular gyrus (ANG), a subregion of posterior lateral parietal cortex. However, typical decoding approaches provide little insight into the nature of ANG content representations. Here, we tested whether complex, multidimensional stimuli (faces) could be reconstructed from ANG by predicting underlying face components from fMRI activity patterns in humans. Using an approach inspired by computer vision methods for face recognition, we applied principal component analysis to a large set of face images to generate eigenfaces. We then modeled relationships between eigenface values and patterns of fMRI activity. Activity patterns evoked by individual faces were then used to generate predicted eigenface values, which could be transformed into reconstructions of individual faces. We show that visually perceived faces were reliably reconstructed from activity patterns in occipitotemporal cortex and several lateral parietal subregions, including ANG. Subjective assessment of reconstructed faces revealed specific sources of information (e.g., affect and skin color) that were successfully reconstructed in ANG. Strikingly, we also found that a model trained on ANG activity patterns during face perception was able to successfully reconstruct an independent set of face images that were held in memory. Together, these findings provide compelling evidence that ANG forms complex, stimulus-specific representations that are reflected in activity patterns evoked during perception and remembering. SIGNIFICANCE STATEMENT: Neuroimaging studies have consistently implicated lateral parietal cortex in episodic remembering, but the functional contributions of lateral parietal cortex to memory remain a topic of debate. Here, we used an innovative form of fMRI pattern analysis to test whether lateral parietal cortex actively represents the contents of memory. Using a large set of human face images, we first extracted latent face components (eigenfaces). We then used machine learning algorithms to predict face components from fMRI activity patterns and, ultimately, to reconstruct images of individual faces. We show that activity patterns in a subregion of lateral parietal cortex, the angular gyrus, supported successful reconstruction of perceived and remembered faces, confirming a role for this region in actively representing remembered content. PMID- 27251625 TI - Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain. AB - Maternal inflammation during pregnancy affects placental function and is associated with increased risk of neurodevelopmental disorders in the offspring. The molecular mechanisms linking placental dysfunction to abnormal fetal neurodevelopment remain unclear. During typical development, serotonin (5-HT) synthesized in the placenta from maternal l-tryptophan (TRP) reaches the fetal brain. There, 5-HT modulates critical neurodevelopmental processes. We investigated the effects of maternal inflammation triggered in midpregnancy in mice by the immunostimulant polyriboinosinic-polyribocytidylic acid [poly(I:C)] on TRP metabolism in the placenta and its impact on fetal neurodevelopment. We show that a moderate maternal immune challenge upregulates placental TRP conversion rapidly to 5-HT through successively transient increases in substrate availability and TRP hydroxylase (TPH) enzymatic activity, leading to accumulation of exogenous 5-HT and blunting of endogenous 5-HT axonal outgrowth specifically within the fetal forebrain. The pharmacological inhibition of TPH activity blocked these effects. These results establish altered placental TRP conversion to 5-HT as a new mechanism by which maternal inflammation disrupts 5 HT-dependent neurogenic processes during fetal neurodevelopment. SIGNIFICANCE STATEMENT: The mechanisms linking maternal inflammation during pregnancy with increased risk of neurodevelopmental disorders in the offspring are poorly understood. In this study, we show that maternal inflammation in midpregnancy results in an upregulation of tryptophan conversion to serotonin (5-HT) within the placenta. Remarkably, this leads to exposure of the fetal forebrain to increased concentrations of this biogenic amine and to specific alterations of crucially important 5-HT-dependent neurogenic processes. More specifically, we found altered serotonergic axon growth resulting from increased 5-HT in the fetal forebrain. The data provide a new understanding of placental function playing a key role in fetal brain development and how this process is altered by adverse prenatal events such as maternal inflammation. The results uncover important future directions for understanding the early developmental origins of mental disorders. PMID- 27251630 TI - Divisive Normalization Predicts Adaptation-Induced Response Changes in Macaque Inferior Temporal Cortex. AB - Stimulus repetition alters neural responses to the repeated stimulus. This so called adaptation phenomenon has been commonly observed at multiple spatial and temporal scales and in different brain areas, and has been hypothesized to affect the neural representation of the sensory input. Yet, the neural mechanisms underlying adaptation still remain unclear, especially in higher-order cortical areas. Here we employ a divisive normalization model of neural responses to predict adaptation-induced changes in responses of single neurons in the macaque inferior temporal (IT) cortex. According to this model, the response of a neuron is determined by an interplay between its direct excitatory and divisive normalizing inputs, with each input being subject to adaptation. To test the model, we recorded the responses of single IT cortex neurons to complex visual stimuli while separately adapting the two putative types of input to those neurons. We compared the changes in responses of these neurons following such adaptation with predictions derived from the divisive normalization model. As predicted by the model, we show that adaptation in the IT cortex can, depending on the relative strength of each putative type of input to a neuron, suppress or enhance the neural response to a complex stimulus. More generally, our data suggest that adaptation serves to selectively enhance processing of the stimuli that differ from recently experienced ones, even when these occur within a configuration of multiple stimuli. SIGNIFICANCE STATEMENT: Stimulus repetition alters neural responses to the repeated stimulus. This so-called adaptation phenomenon has been robustly demonstrated in brains of different species and is considered to be a form of short-term plasticity inherent to the processing of sensory stimuli. Nevertheless, the functional role and underlying mechanisms of adaptation remain unclear. Here we demonstrate that divisive normalization, a canonical neural computation operating throughout the brain, predicts the adaptation-induced changes in response of single neurons to complex stimulus configurations in the macaque inferotemporal cortex. Our findings embed adaptation effects of inferotemporal neurons into the context of a broader neural network perspective that includes divisive normalization. Additionally, our findings have implications for understanding of the function of adaptation in higher-order sensory cortices. PMID- 27251628 TI - Functional Evidence for a Cerebellar Node of the Dorsal Attention Network. AB - The "dorsal attention network" or "frontoparietal network" refers to a network of cortical regions that support sustained attention and working memory. Recent work has demonstrated that cortical nodes of the dorsal attention network possess intrinsic functional connections with a region in ventral cerebellum, in the vicinity of lobules VII/VIII. Here, we performed a series of task-based and resting-state fMRI experiments to investigate cerebellar participation in the dorsal attention network in humans. We observed that visual working memory and visual attention tasks robustly recruit cerebellar lobules VIIb and VIIIa, in addition to canonical cortical dorsal attention network regions. Across the cerebellum, resting-state functional connectivity with the cortical dorsal attention network strongly predicted the level of activation produced by attention and working memory tasks. Critically, cerebellar voxels that were most strongly connected with the dorsal attention network selectively exhibited load dependent activity, a hallmark of the neural structures that support visual working memory. Finally, we examined intrinsic functional connectivity between task-responsive portions of cerebellar lobules VIIb/VIIIa and cortex. Cerebellum to-cortex functional connectivity strongly predicted the pattern of cortical activation during task performance. Moreover, resting-state connectivity patterns revealed that cerebellar lobules VIIb/VIIIa group with cortical nodes of the dorsal attention network. This evidence leads us to conclude that the conceptualization of the dorsal attention network should be expanded to include cerebellar lobules VIIb/VIIIa. SIGNIFICANCE STATEMENT: The functional participation of cerebellar structures in nonmotor cortical networks remains poorly understood and is highly understudied, despite the fact that the cerebellum possesses many more neurons than the cerebral cortex. Although visual attention paradigms have been reported to activate cerebellum, many researchers have largely dismissed the possibility of a cerebellar contribution to attention in favor of a motor explanation, namely, eye movements. The present study demonstrates that a cerebellar subdivision (mainly lobules VIIb/VIIIa), which exhibits strong intrinsic functional connectivity with the cortical dorsal attention network, also closely mirrors a myriad of cortical dorsal attention network responses to visual attention and working memory tasks. This evidence strongly supports a reconceptualization of the dorsal attention network to include cerebellar lobules VIIb/VIIIa. PMID- 27251629 TI - Dynamin 1- and 3-Mediated Endocytosis Is Essential for the Development of a Large Central Synapse In Vivo. AB - Dynamin is a large GTPase crucial for endocytosis and sustained neurotransmission, but its role in synapse development in the mammalian brain has received little attention. We addressed this question using the calyx of Held (CH), a large nerve terminal in the auditory brainstem in mice. Tissue-specific ablation of different dynamin isoforms bypasses the early lethality of conventional knock-outs and allows us to examine CH development in a native brain circuit. Individual gene deletion of dynamin 1, a primary dynamin isoform in neurons, as well as dynamin 2 and 3, did not affect CH development. However, combined tissue-specific knock-out of both dynamin 1 and 3 (cDKO) severely impaired CH formation and growth during the first postnatal week, and the phenotypes were exacerbated by further additive conditional knock-out of dynamin 2. The developmental defect of CH in cDKO first became evident on postnatal day 3 (P3), a time point when CH forms and grows abruptly. This is followed by a progressive loss of postsynaptic neurons and increased glial infiltration late in development. However, early CH synaptogenesis before protocalyx formation was not altered in cDKO. Functional maturation of synaptic transmission in the medial nucleus of the trapezoid body in cDKO was impeded during development and accompanied by an increase in the membrane excitability of medial nucleus of the trapezoid body neurons. This study provides compelling genetic evidence that CH formation requires dynamin 1- and 3-mediated endocytosis in vivo, indicating a critical role of dynamin in synaptic development, maturation, and subsequent maintenance in the mammalian brain. SIGNIFICANCE STATEMENT: Synaptic development has been increasingly implicated in numerous brain disorders. Dynamin plays a crucial role in clathrin-mediated endocytosis and synaptic transmission at nerve terminals, but its potential role in synaptic development in the native brain circuitry is unclear. Using the calyx of Held, a giant nerve terminal in the mouse brainstem, we evaluated the role of dynamin in this process by using tissue specific knock-out (KO) of three different dynamin isoforms (dynamin 1, 2, and 3) individually and in combination. Our data demonstrated that dynamin is required for the formation, functional maturation, and subsequent survival of the calyx of Held. This study highlights the important role of dynamin-mediated endocytosis in the development of central synapses in the mammalian brain. PMID- 27251631 TI - Disruption of Fixation Reveals Latent Sensorimotor Processes in the Superior Colliculus. AB - Executive control of voluntary movements is a hallmark of the mammalian brain. In the gaze-control network, this function is thought to be mediated by a critical balance between neurons responsible for generating movements and those responsible for fixating or suppressing movements, but the nature of this balance between the relevant elements-saccade-generating and fixation-related neurons remains unclear. Specifically, it has been debated whether the two functions are necessarily coupled (i.e., push-and-pull) or independently controlled. Here we show that behavioral perturbation of ongoing fixation with the trigeminal blink reflex in monkeys (Macaca mulatta) alters the effective balance between fixation and saccade-generating neurons in the superior colliculus (SC) and can lead to premature gaze shifts reminiscent of compromised inhibitory control. The shift in balance is primarily driven by an increase in the activity of visuomovement neurons in the caudal SC, and the extent to which fixation-related neurons in the rostral SC play a role seems to be linked to the animal's propensity to make microsaccades. The perturbation also reveals a hitherto unknown feature of sensorimotor integration: the presence of a hidden visual response in canonical movement neurons. These findings offer new insights into the latent functional interactions, or lack thereof, between components of the gaze-control network, suggesting that the perturbation technique used here may prove to be a useful tool for probing the neural mechanisms of movement generation in executive function and dysfunction. SIGNIFICANCE STATEMENT: Eye movements are an integral part of how we explore the environment. Although we know a great deal about where sensorimotor transformations leading to saccadic eye movements are implemented in the brain, less is known about the functional interactions between neurons that maintain gaze fixation and neurons that program saccades. In this study, we used a novel approach to study these interactions. By transient disruption of fixation, we found that activity of saccade-generating neurons can increase independently of modulation in fixation-related neurons, which may occasionally lead to premature movements mimicking lack of impulse control. Our findings support the notion of a common pathway for sensory and movement processing and suggest that impulsive movements arise when sensory processes become "motorized." PMID- 27251632 TI - Role of SGK1 for fatty acid uptake, cell survival and radioresistance of NCI-H460 lung cancer cells exposed to acute or chronic cycling severe hypoxia. AB - BACKGROUND: Unsaturated fatty acids (FA) are required for cancer cell growth. In normoxia cells can generate unsaturated FA from saturated stearic and palmitic acid by desaturation. However, since the desaturation step is oxygen-dependent hypoxic cancer cells display an increased dependence on the uptake of unsaturated FA. Up to now the mechanism of increased FA uptake in hypoxia is largely unknown. Here we aimed to study the role of human serum and glucocorticoid-inducible kinase (SGK1) in the regulation of FA uptake in cancer cells exposed to acute or chronic cycling hypoxia and explore its use as target for the radiosensitization of hypoxic cancer cells. METHODS: The effect of SGK1-inhibition (GSK650394) on NCI-H460 lung adenocarcinoma cells exposed to normoxia, acute or chronic cycling hypoxia was analyzed under standard and serum-deprived conditions by short-term proliferation, apoptosis and cell death assays. The impact of SGK1-inhibition on radiation sensitivity was determined by standard colony formation assays. The effect of GSK650394 on FA uptake was quantified by measuring intracellular accumulation of fluorescent FA (C1-BODIPY(r)-C12). RESULTS: Exposure to acute or chronic cycling hypoxia was associated with up-regulated expression of SGK1 in NCI-H460 cells, increased uptake of FA from the culture medium, and increased sensitivity to serum deprivation. Survival of serum-deprived hypoxic NCI-H460 cells was rescued by the addition of the unsaturated FA, oleic acid, whereas the saturated FA, palmitic acid was highly toxic to the hypoxic cancer cells. Interestingly, SGK1 inhibition abrogated the rescue effect of oleic acid in serum deprived hypoxic cancer cells and this effect was associated with a reduction in FA uptake particularly in anoxia-tolerant cancer cells exposed to severe hypoxia. Finally, SKG1 inhibition decreased long-term survival and potently sensitized the parental and anoxia-tolerant NCI-H460 cells to the cytotoxic effects of ionizing radiation in normoxia as well as the anoxia-tolerant cancer cells in severe hypoxia. CONCLUSIONS: Our data suggest that SGK1 plays a role in the regulation of FA uptake that becomes essential under conditions of acute or chronic cycling hypoxia. We assume that SGK1 may represent a promising therapeutic target for the eradication of hypoxic cancer cells. PMID- 27251633 TI - "Others Like Me". An Approach to the Use of the Internet and Social Networks in Adolescents and Young Adults Diagnosed with Cancer. AB - The purpose of this study is to improve comprehension about how adolescents and young adults (AYA) diagnosed with cancer use the Internet and social networks to seek information about their illness and to establish relationships between them. A group of 20 AYA patients and survivors of cancer (ages 14 to 29) were interviewed from a qualitative approach. Most of the respondents (N = 16) sought information about their disease on the Internet. They looked for information using search engines (mainly Google) and general concepts as their own cancer name. In general, they did not share the information obtained with their parents or professional healthcare providers. The interviewees think that the information is difficult to understand because of jargon and that it is not aimed at a young audience. All (N = 20) have presence in social networking sites. AYAs with cancer are starting to create content themselves: three started a blog in order to explain their experience to others like them. The study shows that is necessary to increase efforts on adapting content to these age groups in order to help them learn more about their own disease. This may contribute to increment their adherence to treatment and to maintain surveillance of potential consequences and health problems post-treatment. PMID- 27251634 TI - Health Literacy and Health-Care Engagement as Predictors of Shared Decision Making Among Adult Information Seekers in the USA: a Secondary Data Analysis of the Health Information National Trends Survey. AB - The objective of this study is to examine the relationship between health literacy, health-care engagement, and shared decision-making (SDM). We analyzed Health Information National Trends Survey 4 (cycle 3) data for 1604 information seekers who had one or more non-emergency room health-care visits in the previous year. SDM was more than two times higher among adults who "always" versus "usually/sometimes/never" take health information to doctor visits (OR = 2.54; 95 % CI 1.19-5.43). There was a twofold increase in SDM among adults who were "completely/very confident" versus "somewhat/a little/not confident" about finding health information (OR = 2.03; 95 % CI 1.37-3.02). Differences in SDM between adults who understood health information and those who had difficulty understanding health information were not statistically significant (OR = 1.39; 95 % CI 0.93-2.07). A Healthy People 2020 goal is to increase SDM. Previous research has suggested that SDM may improve health outcomes across the continuum of care. Only about half of adults report always being involved in health-care decisions. Even more alarming is the fact that SDM has not increased from 2003 to 2013. Our findings suggest that increasing health literacy has the potential to increase health-care engagement and subsequently increase SDM. Effective intervention strategies are needed to improve health literacy and promote health care engagement. PMID- 27251636 TI - Fast, greener and scalable direct coupling of organolithium compounds with no additional solvents. AB - Although the use of catalytic rather than stoichiometric amounts of metal mediator in cross-coupling reactions between organic halides and organometallic counterparts improves significantly the atom economy and waste production, the use of solvents and stoichiometric generation of main-group byproducts (B, Sn and Zn) hamper the 'greenness' and industrial efficiency of these processes. Here we present a highly selective and green Pd-catalysed cross-coupling between organic halides and organolithium reagents proceeding without additional solvents and with short reaction times (10 min). This method bypasses a number of challenges previously encountered in Pd-catalysed cross-coupling with organolithium compounds such as strict exclusion of moisture, dilution and slow addition. Operational ease of this protocol combines the use of industrially viable catalysts loadings (down to 0.1 mol%), scalability of the process (tested up to 120 mmol) and exceptionally favourable environmental impact (E factors in several cases as low as 1). PMID- 27251635 TI - The rise of angiosperm-dominated herbaceous floras: Insights from Ranunculaceae. AB - The rise of angiosperms has been regarded as a trigger for the Cretaceous revolution of terrestrial ecosystems. However, the timeframe of the rise angiosperm-dominated herbaceous floras (ADHFs) is lacking. Here, we used the buttercup family (Ranunculaceae) as a proxy to provide insights into the rise of ADHFs. An integration of phylogenetic, molecular dating, ancestral state inferring, and diversification analytical methods was used to infer the early evolutionary history of Ranunculaceae. We found that Ranunculaceae became differentiated in forests between about 108-90 Ma. Diversification rates markedly elevated during the Campanian, mainly resulted from the rapid divergence of the non-forest lineages, but did not change across the Cretaceous-Paleogene boundary. Our data for Ranunculaceae indicate that forest-dwelling ADHFs may have appeared almost simultaneously with angiosperm-dominated forests during the mid Cretaceous, whereas non-forest ADHFs arose later, by the end of the Cretaceous terrestrial revolution. Furthermore, ADHFs were relatively unaffected by the Cretaceous-Paleogene mass extinction. PMID- 27251637 TI - Dual-responsive aggregation-induced emission-active supramolecular nanoparticles for gene delivery and bioimaging. AB - Dual-responsive aggregation-induced emission-active supramolecular fluorescent nanoparticles are reported, which have the ability to undergo a unique morphological transition combining with a cooperative optical variation in response to pH and light stimuli. The dynamic supramolecular nanoparticles show excellent biocompatibility and effective plasmid DNA condensation capability, further achieving efficient in vitro gene delivery and bioimaging. PMID- 27251639 TI - Changes in American Adults' Reported Same-Sex Sexual Experiences and Attitudes, 1973-2014. AB - We examined change over time in the reported prevalence of men having sex with men and women having sex with women and acceptance of those behaviors in the nationally representative General Social Survey of U.S. adults (n's = 28,161 33,728, ages 18-96 years), 1972-2014. The number of U.S. adults who had at least one same-sex partner since age 18 doubled between the early 1990s and early 2010s (from 3.6 to 8.7 % for women and from 4.5 to 8.2 % for men). Bisexual behavior (having sex with both male and female partners) increased from 3.1 to 7.7 %, accounting for much of the rise, with little consistent change in those having sex exclusively with same-sex partners. The increase in same-sex partners was larger for women than for men, consistent with erotic plasticity theory. Attitudes toward same-sex sexual behavior also became substantially more accepting, d = .75, between the early 1970s and early 2010s. By 2014, 49 % of American adults believed that same-sex sexual activity was "not wrong at all," up from 11 % in 1973 and 13 % in 1990. Controlling for acceptance reduced, but did not eliminate, the increase in same-sex behavior over time. Mixed effects (hierarchical linear modeling) analyses separating age, time period, and cohort showed that the trends were primarily due to time period. Increases in same-sex sexual behavior were largest in the South and Midwest and among Whites, were mostly absent among Blacks, and were smaller among the religious. Overall, same sex sexual behavior has become both more common (or at least more commonly reported) and more accepted. PMID- 27251638 TI - Metallothionein regulates intracellular zinc signaling during CD4(+) T cell activation. AB - BACKGROUND: The ultra-low redox potential and zinc binding properties of the intracellular pool of mammalian metallothioneins (MT) suggest a role for MT in the transduction of redox signals into intracellular zinc signals. Increased expression of MT after exposure to heavy metals, oxidative stress, or inflammatory cytokines leads to an increased intracellular redox-mobilizable zinc pool that can affect downstream zinc-sensitive signaling pathways. CD4(+) T helper cells are poised to be influenced by MT transduced zinc signaling because they produce intracellular reactive oxygen species following activation through the T cell receptor and are sensitive to small changes in intracellular [Zn(2+)]. RESULTS: MT expression and intracellular [Zn(2+)] are both increased during primary activation and expansion of naive CD4(+) T cells into the Tr1 phenotype in vitro. When Tr1 cells from wildtype mice are compared with congenic mice lacking functional Mt1 and Mt2 genes, the expression of intracellular MT is associated with a greater increase in intracellular [Zn(2+)] immediately following exposure to reactive oxygen species or upon restimulation through the T cell receptor. The release of Zn(2+) from MT is associated with a greater increase in p38 MAPK activation following restimulation and decreased p38 MAPK activation in MT knockout Tr1 cells can be rescued by increasing intracellular [Zn(2+)]. Additionally, IL-10 secretion is increased in MT knockout Tr1 cells compared with wildtype controls and this increase is prevented when the intracellular [Zn(2+)] is increased experimentally. CONCLUSIONS: Differences in zinc signaling associated with MT expression appear to be a result of preferential oxidation of MT and concomitant release of Zn(2+). Although zinc is released from many proteins following oxidation, release is greater when the cell contains an intracellular pool of MT. By expressing MT in response to certain environmental conditions, CD4(+) T cells are able to more efficiently release intracellular zinc and regulate signaling pathways following stimulation. The link between MT expression and increased zinc signaling following activation represents an important immunomodulatory mechanism of MT and illuminates the complex role MT plays in shaping immune responses. PMID- 27251640 TI - Perceptions of Sex, Gender, and Puberty Suppression: A Qualitative Analysis of Transgender Youth. AB - International guidelines recommend the use of Gonadotropin-Releasing Hormone (GnRH) agonists in adolescents with gender dysphoria (GD) to suppress puberty. Little is known about the way gender dysphoric adolescents themselves think about this early medical intervention. The purpose of the present study was (1) to explicate the considerations of gender dysphoric adolescents in the Netherlands concerning the use of puberty suppression; (2) to explore whether the considerations of gender dysphoric adolescents differ from those of professionals working in treatment teams, and if so in what sense. This was a qualitative study designed to identify considerations of gender dysphoric adolescents regarding early treatment. All 13 adolescents, except for one, were treated with puberty suppression; five adolescents were trans girls and eight were trans boys. Their ages ranged between 13 and 18 years, with an average age of 16 years and 11 months, and a median age of 17 years and 4 months. Subsequently, the considerations of the adolescents were compared with views of clinicians treating youth with GD. From the interviews with the gender dysphoric adolescents, three themes emerged: (1) the difficulty of determining what is an appropriate lower age limit for starting puberty suppression. Most adolescents found it difficult to define an appropriate age limit and saw it as a dilemma; (2) the lack of data on the long-term effects of puberty suppression. Most adolescents stated that the lack of long-term data did not and would not stop them from wanting puberty suppression; (3) the role of the social context, for which there were two subthemes: (a) increased media-attention, on television, and on the Internet; (b) an imposed stereotype. Some adolescents were positive about the role of the social context, but others raised doubts about it. Compared to clinicians, adolescents were often more cautious in their treatment views. It is important to give voice to gender dysphoric adolescents when discussing the use of puberty suppression in GD. Otherwise, professionals might act based on assumptions about adolescents' opinions instead of their actual considerations. We encourage gathering more qualitative research data from gender dysphoric adolescents in other countries. PMID- 27251641 TI - A Plea for Scientific Ambitions: Reply to Commentaries from Martin Wieser, Nikolai Veresov, Asger Neumann, and Peter Krojgaard. AB - The paper is a reply to commentaries to "Activity theories and the Ontology of Psychology: Learning from Danish and Russian Experiences" (Mammen and Mironenko 2015). At the same time it is an attempt to reply to more general issues raised by the commentators and an attempt to further develop some general ideas from our paper with a focus on the introduction of the new analytical concepts sense and choice categories. These concepts have been elaborated in an axiomatic frame in (Mammen 2016) and the present paper is thus also pointing forwards to that and supporting it with examples from research on adult human relations of love and affection and on infant cognitive development. A few examples from myth and literature are referred to also. The ambition is to introduce new analytical tools across schools and domains of psychology which open for theoretical inclusion of new phenomena and re-structuring of well-known ones. The hope is to surmount some problems, as e.g. the dilemma between dualism and reductionism, which have been obstacles in the search for conceptual and methodological coherence in psychology. In the first place the hope is also to sharpen the analytical, critical and practical potential of psychology as a science. The ambition is not, here and now, to develop a comprehensive general theory as a container for the huge amount of empirical results collected using very heterogeneous criteria for what belongs to the domain of psychology and very heterogeneous conceptual frames. Here we still need some patience following the lesson from natural science, step by step including new domains as the conceptual and practical frames are expanding, but on the other hand not excluding anything apriori. PMID- 27251642 TI - Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery. AB - PURPOSE: Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune checkpoints and other markers of tumor-related immunity in resected NSCLC patients. MATERIALS AND METHODS: All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease free survival (DFS) considering a median follow-up of 16.2 months. RESULTS: Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84-14.01 %), CD8-TILs of 2.9 % (range: 0.11-11.92 %), PD-1 of 0.65 % (range: 0.02-5.87 %), and PD-L1 of 0.7 % (range: 0.03-10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1 (rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho = 0.45; p = 0.001), CD8 TILs and PD-L1 (rho = 0.41; p = 0.003), CD68-TAMs and PD-L1 (rho = 0.30; p = 0.027), PD-1 and PD-L1 (rho = 0.26; p = 0.059). With respect to patients' outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p = 0.002, 0.004, and <0.001, respectively). CONCLUSIONS: The present study shows a direct association between metabolic parameters on FDG PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors. PMID- 27251643 TI - Evaluation of tumour hypoxia during radiotherapy using [18F]HX4 PET imaging and blood biomarkers in patients with head and neck cancer. AB - BACKGROUND AND PURPOSE: Increased tumour hypoxia is associated with a worse overall survival in patients with head and neck squamous cell carcinoma (HNSCC). The aims of this study were to evaluate treatment-associated changes in [18F]HX4 PET, hypoxia-related blood biomarkers, and their interdependence. MATERIAL AND METHODS: [18F]HX4-PET/CT scans of 20 patients with HNSCC were acquired at baseline and after +/-20Gy of radiotherapy. Within the gross-tumour-volumes (GTV; primary and lymph nodes), mean and maximum standardized uptake values, the hypoxic fraction (HF) and volume (HV) were calculated. Also, the changes in spatial uptake pattern were evaluated using [18F]HX4-PET/CT imaging. For all patients, the plasma concentration of CAIX, osteopontin and VEGF was assessed. RESULTS: At baseline, tumour hypoxia was detected in 69 % (22/32) of the GTVs. During therapy, we observed a significant decrease in all image parameters. The HF decreased from 21.7 +/- 19.8 % (baseline) to 3.6 +/- 10.0 % (during treatment; P < 0.001). Only two patients had a HV > 1 cm3 during treatment, which was located for >98 % within the baseline HV. During treatment, no significant changes in plasma CAIX or VEGF were observed, while osteopontin was increased. CONCLUSIONS: [18F]HX4-PET/CT imaging allows monitoring changes in hypoxia during (chemo)radiotherapy whereas the blood biomarkers were not able to detect a treatment-associated decrease in hypoxia. PMID- 27251644 TI - The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy. AB - PURPOSE: The purpose of this study was to prospectively investigate reoxygenation in the early phase of fractionated radiotherapy and serial changes of tumoricidal effects associated with intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer (HNC) using F-18 fluoromisonidazole (FMISO) PET and F 18 fluorodeoxyglucose (FDG) PET. METHODS: Patients with untreated HNC underwent FMISO-PET and FDG-PET studies prospectively. A PET evaluation was conducted before each IMRT (Pre-IMRT), during IMRT (at 30 Gy/15 fr) (Inter-IMRT), and after completion of IMRT (70 Gy/35 fr) (Post-IMRT). FMISO-PET images were scanned by a PET/CT scanner at 4 h after the FMISO injection. We quantitatively analyzed the FMISO-PET images of the primary lesion using the maximum standardized uptake (SUVmax) and tumor-to-muscle ratio (TMR). The hypoxic volume (HV) was calculated as an index of tumor hypoxia, and was defined as the volume when the TMR was >= 1.25. Each FDG-PET scan was started 1 h after injection. The SUVmax and metabolic tumor volume (MTV) values obtained by FDG-PET were analyzed. RESULTS: Twenty patients finished the complete PET study protocol. At Pre-IMRT, 19 patients had tumor hypoxia in the primary tumor. In ten patients, the tumor hypoxia disappeared at Inter-IMRT. Another seven patients showed the disappearance of tumor hypoxia at Post-IMRT. Two patients showed tumor hypoxia at Post-IMRT. The FMISO-PET results showed that the reduction rates of both SUVmax and TMR from Pre IMRT to Inter-IMRT were significantly higher than the corresponding reductions from Inter-IMRT to Post-IMRT (SUVmax: 27 % vs. 10 %, p = 0.025; TMR: 26 % vs. 12 %, p = 0.048). The reduction rate of SUVmax in FDG-PET from Pre-IMRT to Inter IMRT was similar to that from Inter-IMRT to Post-IMRT (47 % vs. 48 %, p = 0.778). The reduction rate of the HV in FMISO-PET from Pre-IMRT to Inter-IMRT tended to be larger than that from Inter-IMRT to Post-IMRT (63 % vs. 40 %, p = 0.490). Conversely, the reduction rate of the MTV in FDG-PET from Pre-IMRT to Inter-IMRT was lower than that from Inter-IMRT to Post-IMRT (47 % vs. 74 %, p = 0.003). CONCLUSIONS: Both the intensity and the volume of tumor hypoxia rapidly decreased in the early phase of radiotherapy, indicating reoxygenation of the tumor hypoxia. In contrast, the FDG uptake declined gradually with the course of radiotherapy, indicating that the tumoricidal effect continues over the entire course of radiation treatment. PMID- 27251645 TI - Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology. AB - Retinopathy of prematurity (ROP) continues to be a major preventable cause of blindness and visual handicaps globally. With improved perinatal care, improved survival of moderately preterm infants, and limited resources for oxygen delivery and monitoring, more mature preterm infants are developing severe ROP in developing countries. The pathophysiology of ROP is characterized by two phases. Phase I ROP is due to vaso-obliteration beginning immediately after birth secondary to a marked decrease in vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). Phase II begins around 33 weeks' postmenstrual age (PMA). During this phase, VEGF levels increase, especially if there is retinal hypoxia with increasing retinal metabolism and demand for oxygen leading to abnormal vasoproliferation. Since the original description of ROP in 1942 by Terry et al. [Am J Ophthalmol 1942;25:203-204], four epidemics of ROP have been observed. Prevention or early treatment of ROP involves careful titration of oxygen saturation by pulse oximeter (SpO2). Optimal SpO2 target remains elusive. Most of the large trials have focused on either a low SpO2 (85 89%) or a high SpO2 (91-95%) from the first day of birth to 36 weeks' PMA. Although the incidence of severe ROP and bronchopulmonary dysplasia decreased significantly, predischarge mortality was higher in these studies. Use of graded SpO2 during the 2 different phases of ROP (early, low SpO2 during phase I vs. late, high SpO2 during phase II) may be the best approach to prevent this disabling condition. Further trials should focus on this strategy. Other biological agents that are currently being studied include IGF-1 with IGF-binding protein-3 (rhIGF-1 + rhIGFBP-3) and propranolol. For advanced stages of ROP, laser ablation of avascular retina, early treatment of ROP (ETROP) protocol, intravitreal injection of anti-VEGF antibodies (e.g. bevacizumab) and vitrectomy are used to protect central vision and prevent retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally. PMID- 27251646 TI - Patient satisfaction with extended-interval warfarin monitoring. AB - Extended-interval monitoring of warfarin has been proposed to reduce follow-up burden and improve patient satisfaction. We aimed to make an initial assessment of anticoagulation satisfaction before and after an extended-interval warfarin monitoring intervention. We conducted a translational prospective single-arm pilot study of extended-interval warfarin monitoring in five pharmacist-managed anticoagulation clinics. Patients meeting CHEST guideline criteria for extended interval warfarin monitoring began progressive extended-interval follow-up (6, 8, and 12 weeks thereafter). The Duke Anticoagulation Satisfaction Scale (DASS) was administered at baseline and at end-of-study or study removal (in patients no longer appropriate for extended interval follow-up). Forty-six patients had evaluable pre- and post-intervention DASS survey data. Mean age of patients was 66.5 years, 74 % were non-Hispanic whites, and 48 % were men. Patients completed a mean +/- SD of 34 +/- 22 weeks of follow-up. Mean +/- SD total DASS score at baseline was 45.2 +/- 14.2 versus 49.1 +/- 14.9 at end-of-study (mean change, +3.9 [95 % CI -0.6-8.4; p = 0.09]), indicating no benefit-and trending toward decrement-to anticoagulation satisfaction. Change in anticoagulation satisfaction varied substantially following extended-interval monitoring, with no evidence of improved satisfaction. Plausible reasons for patients not preferring extended interval monitoring include increased anxiety and disengagement from self management activities, both potentially related to less frequent feedback and reassurance during extended interval-monitoring. Additional research is needed to identify who is likely to benefit most from extended-interval monitoring. Anticoagulation satisfaction should be considered with clinical factors and shared-decision making when implementing extended-interval warfarin monitoring. PMID- 27251647 TI - MRI and the distribution of bone marrow fat in hip osteoarthritis. AB - PURPOSE: To characterize the distribution of bone marrow fat in hip osteoarthritis (OA) using magnetic resonance imaging (MRI) and to assess its use as a potential biomarker. MATERIALS AND METHODS: In all, 67 subjects (39 female, 28 male) with either total hip replacement (THA) or different severities of radiographic OA, assessed by Kellgren-Lawrence grading (KLG), underwent 3T MRI of the pelvis using the IDEAL sequence to separate fat and water signals. Six regions of interest (ROIs) were identified within the proximal femur. Within each ROI the fractional-fat distribution, represented by pixel intensities, was described by its mean, standard deviation, skewness, kurtosis, and entropy. RESULTS: Hips were graded: 12 as severe symptomatic (THA), 33 had KLG0 or 1, 9 were KLG2, 11 with KLG3, and 2 with KLG4 were analyzed together. The fractional fat content in the whole proximal femur did not vary with severity in males (mean (SD) 91.2 (6.0)%) but reduced with severity in females from 89.1 (6.7)% (KLG0,1), 91.5 (2.9)% (KLG2), 85.8 (16.7)% (KLG3,4) to 77.5 (11.9)% (THA) (analysis of variance [ANOVA] P = 0.029). These differences were most pronounced in the femoral head, where mean values fell with OA severity in both sexes from 97.9% (2.5%) (KLG0,1) to 73.0% (25.9%) (THA, P < 0.001) with the largest difference at the final stage. The standard deviation and the entropy of the distribution both increased (P < 0.001). CONCLUSION: Descriptors of the fractional fat distribution varied little with the severity of OA until the most severe stage, when changes appeared mainly in the femoral head, and have, therefore, limited value as biomarkers. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:42-50. PMID- 27251648 TI - Effect of extrusion processing on immune activation properties of hazelnut protein in a mouse model. AB - Although food processing can alter food allergenicity, the impact of extrusion processing on in vivo hazelnut allergenicity is unknown. Here, we tested the hypothesis that extrusion processing will alter the immune activation properties of hazelnut protein (HNP) in mice. Soluble extrusion-processed HNP (EHNP) was prepared and evaluated for immune response using an established transdermal sensitization mouse model. Mice were sensitized with identical amounts of EHNP versus raw HNP. After confirming systemic IgE, IgG1 and IgG2a antibody responses, oral hypersensitivity reaction was quantified by hypothermia shock response (HSR). Mechanism was studied by measuring mucosal mast cell (MMC) degranulation. Compared to raw HNP, the EHNP elicited slower but similar IgE antibody (Ab) response, lower IgG1 but higher IgG2a Ab response. The EHNP exhibited significantly lower oral HSR as well as MMC degranulation capacity. These results demonstrate that the extrusion technology can be used to produce soluble HNP with altered immune activation properties. PMID- 27251649 TI - Ultrasound screening for cholangiocarcinoma could detect premalignant lesions and early-stage diseases with survival benefits: a population-based prospective study of 4,225 subjects in an endemic area. AB - BACKGROUND: Thailand has a high incidence of cholangiocarcinoma (CCA), particularly in the north and northeastern regions. Most CCA patients come at a late, unresectable stage and presently no optimal screening test for CCA has been established. We determined the prevalence of CCA in a remote northern village and explored if screening could lead to early detection and survival benefits. METHODS: A 5-year population-based study was started in October, 2011 for consented Thai individuals, aged 30-60 years. The screening program comprised blood testing, stool examination and serial ultrasonography every 6 months. RESULTS: During the first 3 years, 4,225 eligible individuals were enrolled. CCA was detected in 32 patients, with a mean age of 51.9 years (41-62 years), and 21/32 cases were at a curative resectable stage. The prevalence rate of CCA was 165.7 per 100,000 and one- and two-year incidence rate was 236.7/100,000 and 520.7/100,000, respectively. One- and 2-year overall survival rates of CCA patients were 90.9 and 61.5 %, respectively. Prognosis was better in resectable cases with 100 % 1-year and 77.8 % 2-year survival rates. Interestingly, premalignant pathological lesions (stage 0) were identified in 11 cases with 100 % 3-year survival rate. Serum biomarkers and alkaline phosphatase were not sufficient to detect early-stage disease. In 22 patients, stool samples were positive for Opistorchis viverrini, based on polymerase chain reaction. CONCLUSION: Detection of premalignant lesions and early-stage resectable CCA by ultrasonography resulted in improved clinical outcome. Ultrasonography should be offered as a first screening tool for CCA in an endemic area until other useful biological markers become available. PMID- 27251650 TI - Quantitative measurement of exchange dynamics in proteins via (13)C relaxation dispersion of (13)CHD2-labeled samples. AB - Methyl groups have emerged as powerful probes of protein dynamics with timescales from picoseconds to seconds. Typically, studies involving high molecular weight complexes exploit (13)CH3- or (13)CHD2-labeling in otherwise highly deuterated proteins. The (13)CHD2 label offers the unique advantage of providing (13)C, (1)H and (2)H spin probes, however a disadvantage has been the lack of an experiment to record (13)C Carr-Purcell-Meiboom-Gill relaxation dispersion that monitors millisecond time-scale dynamics, implicated in a wide range of biological processes. Herein we develop an experiment that eliminates artifacts that would normally result from the scalar coupling between (13)C and (2)H spins that has limited applications in the past. The utility of the approach is established with a number of applications, including measurement of ms dynamics of a disease mutant of a 320 kDa p97 complex. PMID- 27251651 TI - Dissociable roles for histone acetyltransferases p300 and PCAF in hippocampus and perirhinal cortex-mediated object memory. AB - The importance of histone acetylation for certain types of memory is now well established. However, the specific contributions of the various histone acetyltransferases to distinct memory functions remain to be determined; therefore, we employed selective histone acetyltransferase protein inhibitors and short-interference RNAs to evaluate the roles of CREB-binding protein (CBP), E1A binding protein (p300) and p300/CBP-associated factor (PCAF) in hippocampus and perirhinal cortex (PRh)-mediated object memory. Rats were tested for short- (STM) and long-term memory (LTM) in the object-in-place task, which relies on the hippocampus and PRh for spatial memory and object identity processing, respectively. Selective inhibition of these histone acetyltransferases by small interfering RNA and pharmacological inhibitors targeting the HAT domain produced dissociable effects. In the hippocampus, CBP or p300 inhibition impaired long term but not short-term object memory, while inhibition of PCAF impaired memory at both delays. In PRh, HAT inhibition did not impair STM, and only CBP and PCAF inhibition disrupted LTM; p300 inhibition had no effects. Messenger RNA analyses revealed findings consistent with the pattern of behavioral effects, as all three enzymes were upregulated in the hippocampus (dentate gyrus) following learning, whereas only CBP and PCAF were upregulated in PRh. These results demonstrate, for the first time, the necessity of histone acetyltransferase activity for PRh mediated object memory and indicate that the specific mnemonic roles of distinctive histone acetyltransferases can be dissociated according to specific brain regions and memory timeframe. PMID- 27251652 TI - Oxidative and nitrative stress and pro-inflammatory cytokines in Mucopolysaccharidosis type II patients: effect of long-term enzyme replacement therapy and relation with glycosaminoglycan accumulation. AB - Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by a deficient activity of iduronate-2-sulfatase, leading to abnormal accumulation of glycosaminoglycans (GAG). The main treatment for MPS II is enzyme replacement therapy (ERT). Previous studies described potential benefits of six months of ERT against oxidative stress in patients. Thus, the aim of this study was to investigate oxidative, nitrative and inflammatory biomarkers in MPS II patients submitted to long term ERT. It were analyzed urine and blood samples from patients on ERT (mean time: 5.2years) and healthy controls. Patients presented increased levels of lipid peroxidation, assessed by urinary 15-F2t-isoprostane and plasmatic thiobarbituric acid-reactive substances. Concerning to protein damage, urinary di-tyrosine (di-Tyr) was increased in patients; however, sulfhydryl and carbonyl groups in plasma were not altered. It were also verified increased levels of urinary nitrate+nitrite and plasmatic nitric oxide (NO) in MPS II patients. Pro-inflammatory cytokines IL-1beta and TNF-alpha were increased in treated patients. GAG levels were correlated to di-Tyr and nitrate+nitrite. Furthermore, IL-1beta was positively correlated with TNF-alpha and NO. Contrastingly, we did not observed alterations in erythrocyte superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, in reduced glutathione content and in the plasmatic antioxidant capacity. Although some parameters were still altered in MPS II patients, these results may suggest a protective role of long-term ERT against oxidative stress, especially upon oxidative damage to protein and enzymatic and non-enzymatic defenses. Moreover, the redox imbalance observed in treated patients seems to be GAG- and pro-inflammatory cytokine-related. PMID- 27251653 TI - Congenital retrosternal hernias of Morgagni: Manifestation and treatment in children. AB - BACKGROUND: Due to scarcity of congenital diaphragmatic hearnias of Morgagni (CDHM), non-specific clinical presentation in the pediatric age group, we aimed to investigate the incidence, clinical manifestations, anatomical characteristics, and develop diagnostic algorithm and treatment of CDHM in children. MATERIALS AND METHODS: The patients' records of children with CDHM treated in our hospital during past 20 years were retrospectively reviewed for the age at diagnosis, gender, clinical findings, anatomical features, operative details and outcome. RESULTS: Since 1995 to 2014 we observed 6 (3 boys, 3 girls) patients with CDHM, that comprise 3.2% of all congenital diaphragmatic hernia cases (n = 185). Age at diagnosis varied from 3 mo. to 10y.o. Failure to thrive was main symptom in 4 patients, followed by recurrent respiratory infections (n = 3), dyspnea (n = 3), and gastrointestinal manifestations: constipation (n = 2), abdominal pain (n = 1). Work-up consisted of plain X-ray for all (n = 6), upper GI (n = 3), barium enema (n = 2), sonography (n = 6) and CT (n = 2). Abdominal approach used in 5 patients, and thoracotomy in one. Herniated contents were: liver lobes (n = 4), transverse colon (n = 3) and greater omentum (n = 1). 5 had right-sided lesion, 1- left-sided. Defect repaired using local tissues. Post operative course was uneventful; all patients appeared well during follow-up. CONCLUSION: CDHM is very uncommon anomaly, very occasionally diagnosed at the early age. Failure to thrive and recurrent respiratory infections are most frequent clinical manifestations. In suspected CDHM we advocate the following work-up: plain chest and abdominal X-ray, contrast study (upper GI series or barium enema), ultrasonographic screen and CT scan. Surgical repair via abdominal approach, using local tissues and hernia sac removal is preferred. PMID- 27251654 TI - Diagnostic value of anti-smooth muscle antibodies and liver enzymes in differentiation of extrahepatic biliary atresia and idiopathic neonatal hepatitis. AB - BACKGROUND: We aimed to evaluate the diagnostic value of anti-smooth muscle antibodies (ASMA) and two liver markers (gamma-glutamyl transpeptidase [GGT] and alkaline phosphatase [ALP]) for differentiating between patients with extrahepatic biliary atresia (EHBA) and idiopathic neonatal hepatitis (INH). MATERIALS AND METHODS: During April 2010-2011, all infants at 2 weeks of age who were diagnosed with cholestasis and admitted to Children's Hospital of Tabriz were enrolled. Based on the results of physical examination, laboratory, imaging and pathological studies, neonates were divided into two groups (EHBA and INH). Receiver operating characteristics analysis was used to define sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for ASMA, GGT and ALP. RESULTS: Thirty neonates with cholestasis (18 with EHBA and 12 with INH) and mean age of 54.66 ? 25.86 days were enrolled. Total and direct bilirubin, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and ASMA titres were highly not significant (P > 0.05) in patients with INH. GGT (P = 0.008) and ALP (P = 0.01) had statistically significant differences that were higher in patients with EHBA. The sensitivity, specificity, PPV and NPV, accuracy, LR+ and LR- of SMA in differentiating cases with BA were 66.7%, 75%, 80% 60%, 70%, 2.68 and 0.44, respectively. For GGT, the values were 88.9%, 66.7%, 80%, 80%, 79.1%, 3.08 and 0.31, respectively. Finally, for ALP, the values were 77.8%, 75%, 82.4%, 69.2%, 80%, 2.66 and 0.24, respectively. CONCLUSION: Our study showed that ASMA may be a useful biomarker for differentiation of EHBA from INH. Further studies with larger samples are recommended for confirming the results of this study. PMID- 27251655 TI - Our experience with pre-operative haemostatic assessment of paediatric patients undergoing adenotonsillectomy at Federal Medical Centre, Makurdi. AB - BACKGROUND: In 2-4% of all patients requiring adenoidectomy, tonsillectomy or adenotonsillectomy, pre-operative screening tests for coagulation disorders are indicated to detect surgical bleeding complications. However, because of cost effect on the patients, the usefulness of these tests is being challenged. We therefore highlight our experience in paediatric patients undergoing adenoidectomy, tonsillectomy or both in our centre. PATIENTS AND METHODS: This is a 31/2-year analysis of the data of 165 paediatric patients who had adenoidectomy, tonsillectomy or both over the study period. The data collected included age, sex, procedure done and detailed clinical bleeding history. RESULTS: A total of 165 children had either adenoidectomy or tonsillectomy, or both. There were 76 males and 89 females giving a male to female ratio of 1:1.2. Their ages ranged from 10 months to 18 years. Eighty-five (51.5%) patients had adenotonsillectomy, 48 (29.1%) and 32 (19.4%) had only tonsillectomies and adenoidectomies, respectively. Only 11 (6.7%) families volunteered the history of either prolonged bleeding with minor injury on the skin or occasional slight nose bleeding. Six (3.6%) patients including 3 of the children with positive family history had posttonsillectomy bleed, out of which 4 (66.7%) were moderate whereas the remaining 2 (33.3%) were severe bleeding, which was not statistically significant (P = 0.041). The two cases of severe bleeding had fresh whole blood transfused whereas the rest that had no bleeding issues were discharged home 48 h postoperatively. CONCLUSION: Our experience in this study suggests that detailed bleeding history is necessary as well as pre-operative haemostatic assessment, if available and affordable for paediatric patients undergoing adenotonsillectomy. PMID- 27251656 TI - Is there any correlation between radiologic findings and eradication of symptoms after pyloromyotomy in hypertrophic pyloric stenosis? AB - BACKGROUND: Hypertrophic pyloric stenosis (HPS) is one of the most common gastrointestinal disorders during early infancy, with an incidence of 1-2:1000 live births in the world. In this study, we aimed to investigate the correlation between radiologic findings and eradication of symptoms after pyloromyotomy in HPS. MATERIALS AND METHODS: One hundred and twenty-five (102 boys and 23 girls) patients with suspected infantile HPS were treated surgically by Ramstedt pyloromyotomy between March 21, 2004 and March 20, 2014 at paediatric surgery ward of Tabriz Children's Hospital, Iran. The demographic features, clinical findings, diagnostic work-up, operation type and postoperative specifications of the patients were studied retrospectively. RESULTS: Male to female ratio was 4:1. The patients were 16-90 days of old and the mean age was 39 +/- 1.42 days. The range of pyloric canal length was 7.60-29.00 mm and the mean length was 19.54 +/- 3.42 mm. Pyloric muscle diameter was 2.70-9.00 mm, and the mean diameter was 4.86 +/- 1.14 mm. Seventy-two percent of patients had episodes of vomiting after operation. Mean time of persistence of vomiting after pyloromyotomy was 15.73 +/- 0.15 h. Mean discharge time was 55.22 +/- 0.08 h. Radiologic findings did not show any significant correlation with persistence of vomiting or discharge time. CONCLUSION: The present study revealed that radiographic findings could not predict postoperative symptom eradication after pyloromyotomy in HPS. PMID- 27251657 TI - Paediatric day-case neurosurgery in a resource challenged setting: Pattern and practice. AB - BACKGROUND: It has been generally observed that children achieve better convalescence in the home environment especially if discharged same day after surgery. This is probably due to the fact that children generally tend to feel more at ease in the home environment than in the hospital setting. Only few tertiary health institutions provide routine day-case surgery for paediatric neurosurgical patients in our sub-region. OBJECTIVE: To review the pattern and practice of paediatric neurosurgical day-cases at our hospital. PATIENTS AND METHODS: A prospective study of all paediatric day-case neurosurgeries carried out between June 2011 and June 2014. RESULTS: A total of 53 patients (34 males and 19 females) with age ranging from 2 days to 14 years were seen. Majority of the patients (77.4%) presented with congenital lesions, and the most common procedure carried out was spina bifida repair (32%) followed by ventriculoperitoneal shunt insertion (26.4%) for hydrocephalus. Sixty-eight percentage belonged to the American Society of Anesthesiologists physical status class 2, whereas the rest (32%) belonged to class 1. General anaesthesia was employed in 83% of cases. Parenteral paracetamol was used for intra-operative analgesia for most of the patients. Two patients had post-operative nausea and vomiting and were successfully managed. There was no case of emergency re operation, unplanned admission, cancellation or mortality. CONCLUSION: Paediatric day-case neurosurgery is feasible in our environment. With careful patient selection and adequate pre-operative preparation, good outcome can be achieved. PMID- 27251658 TI - How to manage a late diagnosed Hirschsprung's disease. AB - BACKGROUND: How to manage a late diagnosed Hirschsprung's disease (HD) and how to avoid calibre discrepancy? SUBJECTS AND METHODS: A retrospective study of all patients diagnosed with HD over 2 years in our hospital from January 2009 to December 2012. Data were analysed for clinical presentations, investigations, surgical procedures and post-operative outcome. RESULTS: Fifteen patients, operated by one single surgeon, were included in this study. The mean age was 6 years (2-16 years). Patients had an ultra-short segment type in 4 cases, rectosigmoid type in 9 cases and descending colonic aganglionosis in 2 cases. Rectal wash out was effective in 12 patients. A blowhole transverse colostomy was performed in 2 patients. Twelve patients underwent one single stage endorectal pull-through. Anastomosis incongruence was avoided by a plication procedure never described before. The assessment of post-operative outcomes by the paediatric incontinence and constipation scoring system revealed a normal continence function in all our patients, but 3 patients suffered from soiling secondary to constipation. CONCLUSION: One single stage pull-through can be safe and effective in children with late diagnosed HD. Routine rectal washout is a good way to prepare the colon. In some cases, blowhole colostomy can be an option. Anastomosis incongruence is a challenge; we describe a plication procedure to avoid it. PMID- 27251659 TI - Corrections of diverse forms of lower limb deformities in patients with mucopolysaccharidosis type IVA (Morquio syndrome). AB - BACKGROUND: Thoracolumbar kyphosis has been considered as the first presenting deformity and is often a key diagnostic clue noted in children with mucopolysaccharidosis (MPS) type IV (Morquio's syndrome). However, we observed that the progressive irregularities of the epiphyses of the long bones were the most prominent skeletal pathology, causing effectively the development of diverse forms of lower limbs deformities with extreme variation in age of onset. MATERIALS AND METHODS: Ten patients (seven children and three adults) with an average age of 15 years have been enrolled in this study. Age of diagnosis of MPS IVA has a variable age of onset and a MISLEADING rate of severity. Hip dislocations, genu valgum, protrusio acetabuli and osteoarthritis were the most common lower limbs deformities in these patients. Clinical and radiographic phenotypes were the baseline tools of documentation. Urinary screening and genotypic characterizations have been applied accordingly. RESULTS: Combined pelvic and femoral procedures for hip dislocation, epiphysiodeses and supracondylar osteotomy for genu valgum and hip arthroplasty for protrusio acetabuli have been performed. All patients manifested insufficient activity of N acetylgalactosamine-6-sulphate sulphatase, an enzyme that degrades keratin sulphate and chondroitin-6 sulphate. CONCLUSION: The extensive clinical heterogeneity contributed significantly in the delay in establishing the diagnosis particularly in adult patients with MPS IV. The epiphyseal irregularities of the long bones and the progressive flattening pathology of MPS IV A were the reason to falsely diagnose some patients as spondyloepiphyseal dysplasia congenital and/or tarda. Proximal femoral osteotomy, realignment osteotomy and total hip arthroplasty have been performed for coxa vara, genu valgum and protrusio acetabuli, respectively, in children and adult group of patients. The importance of early diagnosis on MPS IV A is to receive enzyme replacement therapy and plan for other therapeutic measures. PMID- 27251660 TI - Volvulus of the jejunum on cystic lymphangioma: About a clinical case. AB - Intestinal volvulus on mesenteric cysticum lymphangioma (CL) is rare in children. The clinical picture is not very suggestive. We report a case of intestinal volvulus on CL in a 7-year-old girl after an abdominal trauma. Resection and anastomosis were made. The confirmation diagnosis was done by anatomopathological examination. Early diagnosis of intra-abdominal CL will allow avoiding complication. PMID- 27251661 TI - Laparoscopic treatment of adrenal masses in children: Report of two cases and review of literature. AB - Laparoscopic adrenalectomy has become a common alternative to open surgery for the resection of adrenal lesions in adults: The advantages are to provide better exposure of the adrenal gland, diminish soft tissue dissection, decrease morbidity and postoperative pain; however, reporting on the laparoscopic adrenalectomy in paediatric patients has been limited. We present two cases of laparoscopic adrenalectomy performed at our institution in two children, for left adrenal neuroblastoma in a first patient with opsomyoclonus syndrome, and for a right incidentaloma in the second case. According to recent literature, our experience has demonstrated that the laparoscopic adrenalectomy is a feasible procedure in children with small, well-circumscribed adrenal masses: It can be used a safety to treat suspected benign and malignant adrenal masses in children, with minimal morbidity and short hospital stay. The lateral trans-peritoneal approach offers optimal visualisation and good outcomes in terms of minimal discomfort, rapid recovery and excellent cosmesis. However, in the paediatric field, the number of patients is limited, making the learning curve longer. PMID- 27251662 TI - Aneurysmal femoral neck cyst: Report of a paediatric case and review of literature. AB - The aneurysmal bone cyst (ABC) is a benign tumour of children and young adults. It represents approximately 1-2% of all bone tumours. The ABC may develop on all skeletal bones, but the proximal end of the femur is the most common location. The authors report a ABC femoral neck in a child of 13 years. This location is pretty special. Indeed, the fragility of the femoral neck due partly to the pathology itself and secondarily curettage requires a judicious attitude surgical (excisional curettage + bone graft + screw) to prevent the risk of high local recurrence and pathological fracture. PMID- 27251663 TI - A glance at rabies pre-exposure and post-exposure prophylaxis for dog bites. PMID- 27251664 TI - Dietary Fatty Acids: Is it Time to Change the Recommendations? AB - Limiting the saturated fatty acid (SAFA) consumption forms the basis of dietary fat recommendations for heart health, despite several meta-analyses demonstrating no link between dietary SAFA and the risk of cardiovascular disease (CVD). Three experts on dietary fat and health discussed the evidence of reducing SAFA intake at a symposium of the Federation of European Nutrition Societies in Berlin, Germany, October 23, 2015. Ronald P. Mensink, Maastricht University, the Netherlands, discussed the evidence linking dietary fatty acids and CVD risk. He emphasized the importance of the replacement nutrient(s) when SAFA intake is reduced. Julie Lovegrove, University of Reading, UK, addressed the question of whether higher intakes of unsaturated fatty acids are beneficial. She discussed the replacement of SAFA by polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA), noting the reduction in CVD risk with PUFA replacement and in CVD risk markers with MUFA replacement of SAFA. Ursula Schwab, University of Eastern Finland, Kuopio, Finland, discussed the importance of dietary patterns in achieving reduced risk of CVD, observing that several dietary patterns following the principles of a health-promoting diet and adapted to local customs, food preferences and seasonality are effective in reducing the risk of CVD, type 2 diabetes and other chronic diseases. This paper summarizes the symposium presentations. PMID- 27251665 TI - Application of Microneedles to Skin Induces Activation of Epidermal Langerhans Cells and Dermal Dendritic Cells in Mice. AB - An adequate immune response to percutaneous vaccine application is generated by delivery of sufficient amounts of antigen to skin and by administration of toxin adjuvants or invasive skin abrasion that leads to an adjuvant effect. Microneedles penetrate the stratum corneum, the outermost layer of the skin, and enable direct delivery of vaccines from the surface into the skin, where immunocompetent dendritic cells are densely distributed. However, whether the application of microneedles to the skin activates antigen-presenting cells (APCs) has not been demonstrated. Here we aimed to demonstrate that microneedles may act as a potent physical adjuvant for successful transcutaneous immunization (TCI). We prepared samples of isolated epidermal and dermal cells and analyzed the expression of major histocompatibility complex (MHC) class II and costimulatory molecules on Langerhans or dermal dendritic cells in the prepared samples using flow cytometry. The expression of MHC class II and costimulatory molecules demonstrated an upward trend in APCs in the skin after the application of 500- and 300-um microneedles. In addition, in the epidermal cells, application of microneedles induced more effective activation of Langerhans cells than did an invasive tape-stripping (positive control). In conclusion, the use of microneedles is likely to have a positive effect not only as an antigen delivery system but also as a physical technique inducing an adjuvant-like effect for TCI. PMID- 27251666 TI - Blood transfusion strategy and risk of postoperative delirium in nursing homes residents with hip fracture. A post hoc analysis based on the TRIFE randomized controlled trial. AB - OBJECTIVES: To investigate whether a liberal blood transfusion strategy [Hb levels >=11.3 g/dL (7 mmol/L)] reduces the risk of postoperative delirium (POD) on day 10, among nursing home residents with hip fracture, compared to a restrictive transfusion strategy [Hb levels >=9.7 g/dL (6 mmol/L)]. Furthermore, to investigate whether POD influences mortality within 90 days after hip surgery. METHODS: This is a post hoc analysis based on The TRIFE - a randomized controlled trial. Frail anemic patients from the Orthopedic Surgical Ward at Aarhus University Hospital were enrolled consecutively between January 18, 2010 and June 6, 2013. These patients (aged >=65 years) had been admitted from nursing homes for unilateral hip fracture surgery. After surgery, 179 patients were included in this study. On the first day of hospitalization, all enrolled patients were examined for cognitive impairment (assessed by MMSE) and delirium (assessed by CAM). Delirium was also assessed on the tenth postoperative day. RESULTS: The prevalence of delirium was 10 % in patients allocated to a liberal blood transfusion strategy (LB) and 21 % in the group with a restrictive blood transfusion strategy (RB). LB prevents development of delirium on day 10, compared to RB, odds ratio 0.41 (95 % CI 0.17-0.96), p = 0.04. Development of POD on day 10 increased the risk of 90-day death, hazard ratio 3.14 (95 % CI 1.72 5.78), p < 0.001. CONCLUSION: In nursing home residents undergoing surgery for hip fracture, maintaining hemoglobin level above 11.3 g/dL reduces the rate of POD on day 10 compared to a RB. Development of POD is associated with increased mortality. PMID- 27251667 TI - Continuous decline in incidence of distal humeral fracture of older women in Finland. AB - BACKGROUND: Low-trauma fractures (also called osteoporotic fragility fractures or fall-induced fractures) of older adults are a serious public health problem. However, very little population-based information is available on the nationwide numbers, incidences, and especially secular trends of elderly people's low-trauma fractures of the distal humerus. METHODS: We assessed the current trends in the number and incidence of these fractures in 60-year-old or older women in Finland by taking into account all women who were admitted to Finnish hospitals for primary treatment of such fracture in 1970-2014. RESULTS: The annual number of low-trauma distal humeral fractures among Finnish women 60 years of age or older rose over fivefold between 1970 and 1998 (from 42 to 224 fractures), but thereafter, the number decreased down to 198 fractures in 2014. The age-adjusted incidence (per 100,000 persons) of these fractures also increased in 1970-1998 (from 12 to 35) but decreased thereafter to 23 in 2014. The finding was similar in the age-specific patient groups (60-69, 70-79, and 80+): The incidence rose from 1970 till 1998 and decreased thereafter. CONCLUSIONS: The steep rise in the rate of low-trauma distal humeral fractures in 60-year-old or older Finnish women from 1970 till late 1990s has been followed by a clearly declining fracture rate. The exact reasons for this secular change are unknown, but a cohort effect toward improved functional ability among elderly women, as well as measures to prevent falls and alleviate fall severity, could partly explain the phenomenon. PMID- 27251668 TI - Pressurised metered dose inhaler-spacer technique in young children improves with video instruction. AB - The importance of good device technique to maximise delivery of aerosolised medications is widely recognised. Pressurised metered dose inhaler (pMDI)-spacer technique was investigated in 122 children, aged 2-7 years, with asthma. Eight individual steps of device technique were evaluated before and after viewing an instructional video for correct device technique. Video measurements were repeated every three months for nine months. Device technique improved directly after video instruction at the baseline study visit (p < 0.001) but had no immediate effect at subsequent visits. Additionally, pMDI-spacer technique improved with successive visits over one year for the group overall as evidenced by increases in the proportion of children scoring maximal (p = 0.02) and near maximal (p = 0.04) scores. CONCLUSION: Repeated video instruction over time improves inhaler technique in young children. WHAT IS KNOWN: * Correct device technique is considered essential for sufficient delivery of inhaled medication. * Poor inhaler use is common in young asthmatic children using pressurised metered dose inhalers and spacers. What is New: * Video instruction could be used as a strategy to improve device technique in young children. PMID- 27251669 TI - Perinatal practice in extreme premature delivery: variation in Dutch physicians' preferences despite guideline. AB - Decisions at the limits of viability about initiating care are challenging. We aimed to investigate physicians' preferences on treatment decisions, against the background of the 2010 Dutch guideline offering active care from 24(+0/7) weeks of gestational age (GA). Obstetricians' and neonatologists' opinions were compared. An online survey was conducted amongst all perinatal professionals (n = 205) of the 10 Dutch level III perinatal care centers. Response rate was 60 % (n = 122). Comfort care was mostly recommended below 24(+0/7) weeks and intensive care over 26(+0/7) weeks. The professional views varied most at 24 and 25 weeks, with intensive care recommended but comfort care at parental request optional being the median. There was a wide range in perceived lowest limits of GA for interventions as a caesarian section and a neonatologist present at birth. Obstetricians and neonatologists disagreed on the lowest limit providing chest compressions and administering epinephrine for resuscitation. The main factors restricting active treatment were presence of congenital disorders, "small for gestational age" fetus, and incomplete course of corticosteroids. CONCLUSION: There was a wide variety in individually preferred treatment decisions, especially when aspects were not covered in the Dutch guideline on perinatal practice in extreme prematurity. Furthermore, obstetricians and neonatologists did not always agree. WHAT IS KNOWN: * Cross-cultural differences exists in the preferred treatment at the limits of viability * In the Netherlands since 2010, intensive care can be offered starting at 24 (+0/7) weeks gestation What is new: * There was a wide variety in preferred treatment decisions at the limits of viability especially when aspects were not covered in the Dutch national guideline on perinatal practice in extreme prematurity. PMID- 27251670 TI - Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase. AB - Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC. PMID- 27251671 TI - [Choosing wisely in internal medicine]. AB - "Choosing wisely - DGIM" is an initiative of the German Society of Internal Medicine (DGIM) to strengthen the quality of diagnostics and indications for therapy. Aspects of inappropriate patient care are identified based on scientific evidence in collaboration with12 internal medicine and associated societies. Identified aspects are reviewed and endorsed by an interdisciplinary consensus committee. Addressed are those diagnostic and therapeutic measures which are rarely used despite scientific evidence of their usefulness and those which are frequently used although clear evidence exists that the measures are not useful or even harmful. The resulting positive or negative recommendations are intended to support physicians in the assessment of indications. The relevance of the "Choosing wisely - DGIM" initiative is confirmed by a survey involving 4200 members of DGIM. PMID- 27251672 TI - [Individualized treatment of osteoporosis]. AB - Osteoporosis is the most common clinical disorder of bone metabolism. Treatment decisions should be made on an individual basis, taking into consideration the relative benefits and risks in different patient populations. Drug selection should be based on the form (primary/secondary) and severity of osteoporosis, age, sex, the specific contraindications and precautions for using the various available medications, and existing comorbidities. PMID- 27251673 TI - Psoriatic nail involvement and its relationship with distal interphalangeal joint disease. AB - Psoriatic nail disease and distal interphalangeal (DIP) arthritis both are common manifestations of psoriatic arthritis (PsA). Several clinical characteristics are allegedly associated with DIP joint damage, particularly nail psoriasis. However, there is little evidence to substantiate this phenomenon. The purpose of this study is to investigate the relationship between DIP involvement, nail psoriasis and other parameters. A cross-sectional study involved 45 patients from local rheumatology clinic. Four hundred fifty psoriatic fingernails scored, and the radiographs of all these fingers were reviewed to define PsA DIP arthritic changes. 64.4 % patients had nail psoriasis and 35.6 % had DIP arthritis. Univariate analysis identified that swollen joint-count, digits with chronic dactylitis, HLA-B27 status and nail psoriasis were associated with DIP arthritis. Regression model supported that nail disease was the most significant associated factor of DIP arthritis (OR 9.7, p = 0.05). Nail psoriasis was identified in 40.2 % of digits. Pitting (29.6 %), onycholysis (15.1 %), crumbling (8.2 %), nail bed hyperkeratosis (2.0 %) were noted with the mean modified Nail Psoriasis Severity Index of 0.95 +/-1.68. Among all digits, 57 had DIP arthritis while 393 did not. Within DIP joints with PsA radiological change, 59.6 % had nail disease. Chi square test with the Bonferroni correction further supported an association between nail psoriasis and DIP involvement with p value of 0.001. Two specific nail subtypes-crumbling and onycholysis-were found to be significantly associated with DIP disease. A significant proportion of PsA patients had nail involvement and DIP arthritis. PsA patients with nail changes may be more susceptible to DIP disease. PMID- 27251674 TI - A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome. AB - Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a mysterious disorder characterized by periodically recurrent fevers, oropharyngeal inflammation, and adenitis, which mainly affects children, though in very recent times, it has been also recognized in adulthood. We enrolled 115 unrelated pediatric and adult patients with history of periodic fevers who fulfilled the current diagnostic criteria for PFAPA syndrome in three Italian referral centers and highlighted differences between children and adults. Eighty five children and 30 adults were evaluated: the frequency of flares was significantly higher in pediatric cases, while febrile attack duration was significantly longer in adults. Clockwork periodicity of fever and recurrent pharyngitis were more frequently observed in childhood, but no differences were identified for aphthosis and cervical adenopathy. Conversely, joint symptoms, myalgia, headache, fatigue, ocular signs, and rashes were more common in adults. The simultaneous occurrence of two or three cardinal PFAPA signs did not show any statistical difference between the groups, while the occurrence of only one cardinal manifestation was more frequent in adults. Corticosteroids were effective in 98.82 % of children and 88.2 % of adults. Tonsillectomy was rarely performed, resulting effective in only two patients. Our data illustrate the clinical overlap between pediatric and adult cases of PFAPA syndrome. Adults are characterized by a wider repertoire of inflammatory signs, suggesting that onset in adulthood might leave the disease misdiagnosed. Clinicians, not only pediatricians, should take into account this clinical entity in every patient of whatever age suffering from recurrent fevers of unknown origin. PMID- 27251675 TI - Serum decoy receptor 3 levels are associated with the disease activity of MPO ANCA-associated renal vasculitis. AB - Type 17 T-helper (Th17) cells have been suggested to be involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Th17 cell proliferation is promoted by tumor necrosis factor (TNF)-like ligand 1A (TL1A), which binds to death receptor 3 (DR3) expressed on Th17 cells. Decoy receptor 3 (DcR3) is known to block the TL1A-DR3 pathway by binding TL1A. To evaluate the Th17-TL1A systems as disease activity markers in AAV, we investigated the serum levels of TL1A and DcR3 in AAV patients. Serum IL-17, IL 23, TL1A, and DcR3 were measured by ELISA in 24 AAV patients with microscopic polyangiitis before the initial treatment, 24 AAV patients during remission, and 20 control subjects. There were no significant differences in serum IL-17, IL-23, and TL1A levels among the active-vasculitis patients, inactive-vasculitis patients, and controls. The mean serum DcR3 level was significantly higher in the active-vasculitis patients than in the inactive-vasculitis patients and controls (P < 0.0001, respectively). There were significant positive correlations between the serum DcR3 levels and Birmingham Vasculitis Activity Score (BVAS), myeloperoxidase (MPO)-ANCA titers, white blood cell counts, serum creatinine levels, and serum C-reactive protein levels. In a multiple regression analysis, there was a significant positive correlation between the serum DcR3 level and BVAS (beta = 0.650, P = 0.0462). The mean BVAS level was significantly higher in the active-vasculitis patients with high serum DcR3 levels than in those with the low serum DcR3 levels (P = 0.0202). The serum level of DcR3 may be a useful marker for disease activity in AAV. PMID- 27251676 TI - Utility of testing for apraxia and associated features in dementia. AB - INTRODUCTION: Existing literature suggests that the presence or absence of apraxia and associated parietal deficits may be clinically relevant in differential diagnosis of dementia syndromes. AIM: This study investigated the profile of these features in Alzheimer's disease (AD) and frontotemporal dementia (FTD) spectrum disorders, at first presentation. METHODS: Retrospective case note analysis was undertaken in 111 patients who presented to the Oxford Cognitive Disorders Clinic, Oxford, UK, including 29 amnestic AD, 12 posterior cortical atrophy (PCA), 12 logopenic primary progressive aphasia (lvPPA), 20 behavioural variant FTD (bvFTD), 7 non-fluent variant PPA (nfvPPA), 6 semantic variant PPA (svPPA) and 25 patients with subjective cognitive impairment (SCI). The clinical features of interest were: limb apraxia, apraxia of speech (AOS), and left parietal symptoms of dyslexia, dysgraphia, and dyscalculia. RESULTS: The prevalence of limb apraxia was highest in PCA, amnestic AD, lvPPA and nfvPPA. AOS was only observed in nfvPPA. Associated parietal features were more prevalent in AD spectrum than FTD spectrum disorders. Group comparisons between key differential diagnostic challenges showed that lvPPA and nfvPPA could be significantly differentiated on the presence of left parietal features and AOS, and amnestic AD could be differentiated from bvFTD, svPPA and SCI by limb apraxia. Regression analysis showed that limb apraxia could successfully differentiate between AD and FTLD spectrum disorders with 83% accuracy. DISCUSSION: Disease-specific profiles of limb apraxia and associated deficits can be observed. FTD and AD spectrum disorders can be difficult to differentiate due to overlapping cognitive symptoms, and measures of apraxia, in particular, appear to be a promising discriminator. PMID- 27251677 TI - (18)F-FDG uptake by rectal cancer is similar in mucinous and nonmucinous histological subtypes. AB - PURPOSE: PET/CT has been considered limited for the evaluation of mucinous colorectal tumors due to low (18)F-FDG uptake. The aim of our study was to compare PET/CT variables in mucinous (MC) and nonmucinous (NMC) rectal adenocarcinomas. METHODS: Consecutive patients with cT2-4N0-2M0 rectal cancer included in a prospective clinical trial were reviewed. PET/CT was performed for primary baseline staging. Visual and quantitative analysis included SUVmax and SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG). PET/CT parameters were compared according to histological subtypes. RESULTS: Overall, 73 patients were included (18 mucinous and 55 nonmucinous). SUVmax values were similar between MC and NMC (19.7 vs. 16.6; p = 0.5). MTV and TLG values were greater in the MC group (103.9 vs. 54.1; p = 0.007 and 892.5 vs. 358.8; p = 0.020) due to larger tumor volumes of MC. CONCLUSIONS: Metabolic parameters at baseline PET/CT for patients with rectal cancer are similar in mucinous and nonmucinous histological subtypes. PMID- 27251678 TI - Effect of antibrowning dips and controlled atmosphere storage on the physico chemical, visual and nutritional quality of minimally processed "Rojo Brillante" persimmons. AB - The combined effect of antibrowning dips and controlled atmosphere storage on fresh-cut "Rojo Brillante" persimmon quality was investigated. Persimmon slices were dipped in 10 g L-1 ascorbic acid, 10 g L-1 citric acid or water and were stored in different controlled atmospheres at 5 C. Controlled atmosphere conditions were 21 kPa O2 + 10 kPa CO2 (Atm-B), 21 kPa O2 + 20 kPa CO2 (Atm-C), 5 kPa O2 + 10 kPa CO2 (Atm-D) and 5 kPa O2 in the absence of CO2 (Atm-E). Air (Atm A) was used as a control. Atmospheres with high CO2 concentrations induced darkening, associated with a flesh disorder known as "internal flesh browning". Only the samples placed in Atm-E, and treated with 10 g L-1 ascorbic acid or 10 g L-1 citric acid, controlled enzymatic browning, reduced firmness loss and prevented the "internal flesh browning" disorder. The maximum limit of marketability was achieved in the samples treated with 10 g L-1 citric acid and stored in Atm-E for nine storage days at 5 C. The total vitamin C, free radical scavenging activity, total phenolic content and total carotenoids of the fresh cut "Rojo Brillante" persimmons were affected by maturity stage at harvest, whereas antibrowning dips and controlled atmosphere storage had no clear effect. PMID- 27251679 TI - Correction to 'Estimating oxygen distribution from vasculature in three dimensional tumour tissue'. PMID- 27251680 TI - Modelling the transport of environmental DNA through a porous substrate using continuous flow-through column experiments. AB - Detecting environmental DNA (eDNA) in water samples is a powerful tool in determining the presence of rare aquatic species. However, many open questions remain as to how biological and physical conditions in flowing waters influence eDNA. Motivated by what one might find in a stream/river benthos we conducted experiments in continuous flow columns packed with porous substrates to explore eDNA transport and ask whether substrate type and the presence of colonized biofilms plays an important role for eDNA retention. To interpret our data, and for modelling purposes, we began with the assumption that eDNA could be treated as a classical tracer. Comparing our experimental data with traditional transport models, we found that eDNA behaves anomalously, displaying characteristics of a heterogeneous, polydisperse substance with particle-like behaviour that can be filtered by the substrate. Columns were quickly flushed of suspended eDNA particles while a significant amount of particles never made it through and were retained in the column, as calculated from a mass balance. Suspended eDNA was exported through the column, regardless of biofilm colonization. Our results indicate that the variable particle size of eDNA results in stochastic retention, release and transport, which may influence the interpretation eDNA detection in biological systems. PMID- 27251681 TI - Community-based participatory research to improve life quality and clinical outcomes of patients with breast cancer (DianaWeb in Umbria pilot study). AB - INTRODUCTION: Breast cancer (BC) is the most frequent cancer in Europe and the International Agency for Research on Cancer (IARC) has estimated over 460 000 incident cases per year. Survival among patients with BC has increased in the past decades and EUROCARE-5 has estimated a 5-year relative survival rate of 82% for patients diagnosed in 2000-2007. There is growing evidence that lifestyle (such as a diet based on Mediterranean principles associated with moderate physical activity) may influence prognosis of BC; however, this information is not currently available to patients and is not considered in oncology protocols. Only a few epidemiological studies have investigated the role of diet in BC recurrence and metastasis. METHODS AND ANALYSIS: DianaWeb is a community-based participatory research dedicated to patients with BC and represents a collaborative effort between participants and research institutions to determine if specified changes in lifestyle would result in improved outcomes in terms of quality of life or survival. The aim of the study is to recruit a large number of participants, to monitor their lifestyle and health status over time, to provide them tips to encourage sustainable lifestyle changes, to analyse clinical outcomes as a function of baseline risk factors and subsequent changes, and to share with patients methodologies and results. DianaWeb uses a specific interactive website (http://www.dianaweb.org/) and, with very few exceptions, all communications will be made through the web. In this paper we describe the pilot study, namely DianaWeb in Umbria. ETHICS AND DISSEMINATION: DianaWeb does not interfere with prescribed oncological treatments; rather, it recommends that participants should follow the received prescriptions. The results will be used to plan guidelines for nutrition and physical activity for patients with BC. The pilot study was approved by the ethics committee of the University of Perugia (reference number 2015-002), and is supported by Fondazione Cassa di Risparmio di Perugia (2013.0185 021). PMID- 27251682 TI - Identification of responders to inhaled corticosteroids in a chronic obstructive pulmonary disease population using cluster analysis. AB - OBJECTIVES: To identify clusters of patients who may benefit from treatment with an inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) versus LABA alone, in terms of exacerbation reduction, and to validate previously identified clusters of patients with chronic obstructive pulmonary disease (COPD) (based on diuretic use and reversibility). DESIGN: Post hoc supervised cluster analysis using a modified recursive partitioning algorithm of two 1-year randomised, controlled trials of fluticasone furoate (FF)/vilanterol (VI) versus VI alone, with the primary end points of the annual rate of moderate-to-severe exacerbations. SETTING: Global. PARTICIPANTS: 3255 patients with COPD (intent-to treat populations) with a history of exacerbations in the past year. INTERVENTIONS: FF/VI 50/25 ug, 100/25 ug or 200/25 ug, or VI 25 ug; all one time per day. OUTCOME MEASURES: Mean annual COPD exacerbation rate to identify clusters of patients who benefit from adding an ICS (FF) to VI bronchodilator therapy. RESULTS: Three clusters were identified, including two groups that benefit from FF/VI versus VI: patients with blood eosinophils >2.4% (RR=0.68, 95% CI 0.58 to 0.79), or blood eosinophils <=2.4% and smoking history <=46 pack years, experienced a reduced rate of exacerbations with FF/VI versus VI (RR=0.78, 95% CI 0.63 to 0.96), whereas those with blood eosinophils <=2.4% and smoking history >46 pack-years were identified as non-responders (RR=1.22, 95% CI 0.94 to 1.58). Clusters of patients previously identified in the fluticasone propionate/salmeterol (SAL) versus SAL trials of similar design were not validated; all clusters of patients tended to benefit from FF/VI versus VI alone irrespective of diuretic use and reversibility. CONCLUSIONS: In patients with COPD with a history of exacerbations, those with greater blood eosinophils or a lower smoking history may benefit more from ICS/LABA versus LABA alone as measured by a reduced rate of exacerbations. In terms of eosinophils, this finding is consistent with findings from other studies; however, the validity of the 2.4% cut-off and the impact of smoking history require further investigation. TRIAL REGISTRATION NUMBERS: NCT01009463; NCT01017952; Post-results. PMID- 27251684 TI - Evolution of target organ damage and haemodynamic parameters over 4 years in patients with increased insulin resistance: the LOD-DIABETES prospective observational study. AB - OBJECTIVES: We prospectively examined the impact of type 2 diabetes compared with metabolic syndrome (MetS) on the development of vascular disease over 4 years as determined by anatomic and functional markers of vascular disease. By comparing the vascular outcomes of the 2 disorders, we seek to determine the independent effect of elevated glucose levels on vascular disease. SETTING: 2 primary care centres in Salamanca, Spain. PARTICIPANTS: We performed a prospective observational study involving 112 patients (68 with type 2 diabetes and 44 with MetS) who were followed for 4 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Measurements included blood pressure, blood glucose, lipids, smoking, body mass index, waist circumference, Homeostasis Model Assessment Insulin Resistance (HOMA IR), hs-c-reactive protein and fibrinogen levels. We also evaluated vascular, carotid intima media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index, heart and renal target organ damage (TOD). The haemodynamic parameters were central (CAIx) and peripheral (PAIx) augmentation indices. RESULTS: In year 4, participants with type 2 diabetes had increased IMT thickness. These patients had more plaques and an IMT>0.90 mm. In participants with MetS, we only found an increase in the number of plaques. We found no changes in PWV, CAIx and PAIx. The patients with diabetes had a greater frequency of vascular TOD. There were no differences neither in renal nor cardiac percentage of TOD in the patients with MetS or diabetes mellitus type 2. CONCLUSIONS: This prospective study showed that the evolution of vascular TOD is different in participants with type 2 diabetes compared with those with MetS. While IMT and PWV increased in type 2 diabetes, these were not modified in MetS. The renal and cardiac TOD evolution, as well as the PAIx and CAIx, did not change in either group. TRIAL REGISTRATION NUMBER: NCT01065155; Results. PMID- 27251683 TI - Association between white blood cell count and non-alcoholic fatty liver disease in urban Han Chinese: a prospective cohort study. AB - OBJECTIVES: The white blood cell (WBC) count is a simple and convenient marker of inflammation for use in medical practice; however, its association with non alcoholic fatty liver disease (NAFLD) has not been determined. We examined the relationship between WBC and NAFLD to provide a convenient and useful marker for the prediction of NAFLD. SETTING: A longitudinal cohort participating in a large health check-up programme for the Chinese population was selected and followed up from 2005 to 2011. PARTICIPANTS: A total of 21 307 male and female participants without NAFLD who underwent health check-ups at least twice between 2005 and 2011 were included in this study. 15 201 participants (7286 men and 7915 women) were eligible for inclusion. RESULTS: The baseline distribution of age, WBC, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL C), serum total protein (TP), albumin (ALB) and globin (GLO) and the prevalence of males, hypertension, hyperglycaemia, smoking and regular exercise were significantly different between the incident NAFLD and non-NAFLD groups (p<0.05). Cox proportional hazards regression analysis was performed to estimate the HRs and 95% CIs of WBC, which predicted the occurrence of NAFLD. Compared with the lowest WBC quartile (Q1), the HRs and 95% CIs of the other WBC quartiles (Q2, Q3 and Q4) for incident NAFLD were 1.090 (0.978 to 1.215), 1.174 (1.055 to 1.305) and 1.152 (1.035 to 1.281), respectively, after adjusting for age, gender, smoking, regular exercise, BMI, hypertension, hyperglycaemia, TC, TG, HDL-C, LDL C, ALB and GLO. CONCLUSIONS: Our study clearly showed that WBC count was a significant factor associated with incident NAFLD in Han Chinese. PMID- 27251685 TI - Prevalence of metabolic syndrome and its related factors among North Korean refugees in South Korea: a cross-sectional study. AB - OBJECTIVES: To determine the prevalence of metabolic syndrome (MetS) and its related factors among North Korean refugees (NKR) in South Korea. DESIGN: Cross sectional study conducted using a questionnaire and anthropometric and biochemical data on NKR in South Korea. SETTING: Seoul, South Korea. PARTICIPANTS: A sample of NKR who voluntarily underwent medical examinations in Anam Hospital of Korea University, Seoul, South Korea (N=708, consisting of 161 males and 547 females). To compare the prevalence of MetS, 1416 age- and gender matched individuals from the South Korean population (SKP, at a ratio of 1:2 to NKR) were randomly selected from the fifth Korean National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: The prevalence of MetS and its related factors among NKR in South Korea and comparison with its prevalence among the general SKP. RESULTS: The prevalence of MetS among male and female NKR in South Korea was 19.7% and 17.2%, respectively. Although obesity is more prevalent in South than in North Korea, we found no difference in the prevalence of MetS between the female NKR and SKP groups (17.2% vs 16.6%, respectively; p=0.830). As regards the males, the small sample size of the NKR group yielded insufficient evidence of any difference in MetS prevalence between the NKR and SKP groups (19.7% vs 26.2%, respectively; p=0.134). We found that excess weight gain (>=5%) in South Korea was significantly associated with MetS among NKR. CONCLUSIONS: The prevalence of MetS among NKR did not differ from that in the SKP group despite the lower prevalence of obesity in NKR than in the general SKP. The fact that excess weight gain in South Korea was associated with the risk of MetS suggests that public health policy makers should focus on preventing excess weight gain in NKR during resettlement in South Korea. PMID- 27251686 TI - Conflict of interest between professional medical societies and industry: a cross sectional study of Italian medical societies' websites. AB - OBJECTIVE: To describe how Italian medical societies interact with pharmaceutical and medical device industries through an analysis of the information available on their websites. DESIGN: Cross sectional study. SETTING: Italy. PARTICIPANTS: 154 medical societies registered with the Italian Federation of Medical-Scientific Societies. MAIN OUTCOME MEASURES: Indicators of industry sponsorship (presence of industry sponsorship in the programme of the last medical societies' annual conference; presence of manufacturers' logos on the homepage; presence of industry sponsorship of satellite symposia during the last annual conference). RESULTS: 131 Italian medical societies were considered. Of these, 4.6% had an ethical code covering relationships with industry on their websites, while 45.6% had a statute that mentioned the issue of conflict of interest and 6.1% published the annual financial report. With regard to industry sponsorship, 64.9% received private sponsorship for their last conference, 29.0% had manufacturers' logos on their webpage, while 35.9% had industry-sponsored satellite symposia at their last conference. The presence of an ethical code on the societies' websites was associated with both an increased risk of industry sponsorship of the last conference (relative risk (RR) 1.22, 95% CIs 1.01 to 1.48 after adjustment) and of conferences and/or satellite symposia (RR 1.22, 95% CIs 1.02 to 1.48 after adjustment) but not with the presence of manufacturers' logos on the websites (RR 1.79, 95% CIs 0.66 to 4.82 after adjustment). No association was observed with the other indicators of governance and transparency. CONCLUSIONS: This survey shows that industry sponsorship of Italian medical societies' conferences is common, while the presence of a structured regulatory system is not. Disclosure of the amount of industry funding to medical societies is scarce. The level of transparency therefore needs to be improved and the whole relationship between medical societies and industry should be further disciplined in order to avoid any potential for conflict of interest. PMID- 27251687 TI - Validation of chronic obstructive pulmonary disease (COPD) diagnoses in healthcare databases: a systematic review protocol. AB - INTRODUCTION: Healthcare databases are useful sources to investigate the epidemiology of chronic obstructive pulmonary disease (COPD), to assess longitudinal outcomes in patients with COPD, and to develop disease management strategies. However, in order to constitute a reliable source for research, healthcare databases need to be validated. The aim of this protocol is to perform the first systematic review of studies reporting the validation of codes related to COPD diagnoses in healthcare databases. METHODS AND ANALYSIS: MEDLINE, EMBASE, Web of Science and the Cochrane Library databases will be searched using appropriate search strategies. Studies that evaluated the validity of COPD codes (such as the International Classification of Diseases 9th Revision and 10th Revision system; the Real codes system or the International Classification of Primary Care) in healthcare databases will be included. Inclusion criteria will be: (1) the presence of a reference standard case definition for COPD; (2) the presence of at least one test measure (eg, sensitivity, positive predictive values, etc); and (3) the use of a healthcare database (including administrative claims databases, electronic healthcare databases or COPD registries) as a data source. Pairs of reviewers will independently abstract data using standardised forms and will assess quality using a checklist based on the Standards for Reporting of Diagnostic accuracy (STARD) criteria. This systematic review protocol has been produced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 statement. ETHICS AND DISSEMINATION: Ethics approval is not required. Results of this study will be submitted to a peer-reviewed journal for publication. The results from this systematic review will be used for outcome research on COPD and will serve as a guide to identify appropriate case definitions of COPD, and reference standards, for researchers involved in validating healthcare databases. TRIAL REGISTRATION NUMBER: CRD42015029204. PMID- 27251688 TI - Rethinking funding priorities in mental health research. AB - Mental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio. PMID- 27251689 TI - Invited commentary on ... Rethinking funding priorities in mental health research. AB - This commentary takes up the notion proposed by Lewis-Fernandez and colleagues that we need more balance in research priorities. Specifically, our reliance on neurobiology may be misplaced and likely to be unrewarding unless we ensure that: (a) research with better return for patients and the public is also pursued; (b) research findings are put into practice; and (c) we retain a focus on proportionate investment in service provision. Patient, public and economic perspectives should drive the decision making for better investment, and behaviour change might be better targeted at commissioners and policy makers rather than patients and providers. PMID- 27251690 TI - The FDA's failure to address the lack of generalisability of antidepressant efficacy trials in product labelling. AB - According to the US Food and Drug Administration's (FDA's) regulations, the criteria used to select patients into registration studies should be addressed in a product's label. The FDA's labelling guidelines, which specifically indicate that the routine exclusion of patients of a certain level of severity should be noted in the label, has been uniformly ignored. PMID- 27251694 TI - Antoni Kepinski (1918-1972), pioneer of post-traumatic stress disorder - psychiatry in history. PMID- 27251695 TI - Duration of depressive symptoms significantly related to increase in mortality. PMID- 27251696 TI - Authors' reply. PMID- 27251697 TI - Correction. PMID- 27251701 TI - A modified breathing pattern improves the performance of a continuous capnodynamic method for estimation of effective pulmonary blood flow. AB - In a previous study a new capnodynamic method for estimation of effective pulmonary blood flow (COEPBF) presented a good trending ability but a poor agreement with a reference cardiac output (CO) measurement at high levels of PEEP. In this study we aimed at evaluating the agreement and trending ability of a modified COEPBF algorithm that uses expiratory instead of inspiratory holds during CO and ventilatory manipulations. COEPBF was evaluated in a porcine model at different PEEP levels, tidal volumes and CO manipulations (N = 8). An ultrasonic flow probe placed around the pulmonary trunk was used for CO measurement. We tested the COEPBF algorithm using a modified breathing pattern that introduces cyclic end-expiratory time pauses. The subsequent changes in mean alveolar fraction of carbon dioxide were integrated into a capnodynamic equation and effective pulmonary blood flow, i.e. non-shunted CO, was calculated continuously breath by breath. The overall agreement between COEPBF and the reference method during all interventions was good with bias (limits of agreement) 0.05 (-1.1 to 1.2) L/min and percentage error of 36 %. The overall trending ability as assessed by the four-quadrant and the polar plot methodology was high with a concordance rate of 93 and 94 % respectively. The mean polar angle was 0.4 (95 % CI -3.7 to 4.5) degrees . A ventilatory pattern recurrently introducing end-expiratory pauses maintains a good agreement between COEPBF and the reference CO method while preserving its trending ability during CO and ventilatory alterations. PMID- 27251702 TI - Molecular epidemiology and phylogenetic analysis of HA gene of influenza A(H1N1)pdm09 strain during 2010-2014 in Dalian, North China. AB - The objective of the present study was to evaluate the epidemiology of influenza A(H1N1)pdm09 and its hemagglutinin (HA) molecular and phylogenetic analysis during 2010-2014 in Dalian, North China. A total of 3717 influenza-like illness (ILI) cases were tested by real-time PCR and 493 were found to be positive. Out of these 493 cases, 121 were subtype influenza A(H1N1)pdm09, of which 14 cases were reported in 2010-2011, 29 in 2012-2013, and 78 in 2013-2014. HA coding regions of 45 isolates were compared to that of the vaccine strain A/California/7/09(H1N1), and a number of variations were detected. P83S, S185T, S203T, R223Q, and I321V mutations were observed in all of the Dalian isolates. Furthermore, a high proportion >71 % of the strains possessed the variation D97N and K283E. Phylogenetic analysis confirmed the close match of the majority of circulating strains with the vaccine strains. However, it also reveals a trend of strains to accumulate amino acid variations and form new phylogenetic groups. PMID- 27251703 TI - Risk factors for ischaemic colitis after surgery for abdominal aortic aneurysm: a systematic review and observational meta-analysis. AB - BACKGROUND: Ischaemic colitis is an infrequent but serious complication following repair of abdominal aortic aneurysm (AAA), with high mortality rates. This systematic review set out to identify risk factors for the development of ischaemic colitis after AAA surgery. METHODS: A systematic search of the MEDLINE, EMBASE and CINAHL databases was performed. This search was limited to studies published in the English language after 1990. Abstracts were screened by two authors. Eligible studies were obtained as full text for further examination. Data was extracted by two authors, and any disputes were resolved via consensus. Extracted data was pooled using Mantel-Haenszel random effects models. Bias was assessed using two Cochrane-approved tools. Effect sizes are expressed as relative risk ratios alongside the 95 % confidence interval. Statistical significance was defined at the level of p < 0.05. RESULTS: From 388 studies identified in the initial search, 33 articles were included in the final synthesis and analysis. Risk factors were grouped into patient (female gender, disease severity) and operative factors (peri-procedural hypotension, operative modality). The risk of ischaemic colitis was significantly higher when undergoing emergency repair versus elective (risk ratio (RR) 7.36, 3.08 to 17.58, p < 0.001). Endovascular repair reduced the likelihood of ischaemic colitis (RR 0.22, 0.12 to 0.39, p < 0.001). DISCUSSION: The quality of published evidence on this subject is poor with many retrospective datasets and inconsistent reporting across studies. Despite this, emergency presentation and open repair should prompt close monitoring for the development of IC. PMID- 27251704 TI - Aspirin vs Heparin for the Prevention of Preeclampsia. AB - Preeclampsia is a hypertensive disorder of pregnancy that remains a significant cause of maternal morbidity and mortality worldwide. Preeclampsia can be resolved by delivery, and most of the proposed preventive treatment approaches are based on processes involved in placental development in early pregnancy. Yet, none of these has been established in clinical practice. Low-dose aspirin is the most promising candidate, nevertheless; while some individual randomized controlled trials showed minimal or no statistically significant benefit, recent metanalyses showed that early initiation before 16 weeks of gestation is associated with prevention of early-onset preeclampsia and reduction in prevalence of perinatal death or morbidity of pregnant women. Heparin could be an alternative antithrombotic and anti-inflammatory median to prevent preeclampsia either alone or in combination with aspirin; however, results are conflicting concerning efficacy. PMID- 27251705 TI - A Qualitative Study of Factors Affecting Morale in Psychiatry Residency Training. AB - OBJECTIVE: Resident morale is an important yet poorly understood aspect of the residency training experience. Despite implications for program quality, resident satisfaction, patient care, and recruitment, little is known about the variables influencing this complex phenomenon. This study sought to identify important factors affecting morale in psychiatry residency training. METHODS: The authors conducted four semi-structured focus groups at a moderately sized, urban, psychiatry residency program during the 2013-2014 academic year. They used qualitative data analysis techniques, including grounded theory and content analysis, to identify key themes affecting resident morale across training levels. RESULTS: Twenty-seven residents participated in the focus groups with equal distribution across post-graduate years (PGY) 1-4. Five major conceptual categories affecting resident morale emerged: Sense of Community, Individual Motivators, Clinical Work, Feeling Cared For, and Trust in the Administration. CONCLUSIONS: Morale is an important topic in residency education. The qualitative results suggest that factors related to a Sense of Community and Individual Motivators generally enhanced resident morale whereas factors related to a lack of Feeling Cared For and Trust in the Administration tended to contribute to lower morale. The authors describe the possible interventions to promote stronger program morale suggested by these findings. PMID- 27251706 TI - Cardiomyocyte-derived CXCL12 is not involved in cardiogenesis but plays a crucial role in myocardial infarction. AB - The chemokine CXCL12/SDF-1 is crucial for heart development and affects cardiac repair processes due to its ability to attract leukocytes and stem cells to injured myocardium. However, there is a great controversy whether CXCL12 is beneficial or detrimental after myocardial infarction (MI). The divergence in the reported CXCL12 actions may be due to the cellular source and time of release of the chemokine after MI. This study was designed to evaluate the role of cardiomyocyte-derived CXCL12 for cardiogenesis and heart repair after MI. We generated two rodent models each targeting CXCL12 in only one cardiac cell type: cardiomyocyte-specific CXCL12-overexpressing transgenic (Tg) rats and CXCL12 conditional knockout (cKO) mice. Animals of both models did not show any signs of cardiac abnormalities under baseline conditions. After induction of MI, cKO mice displayed preserved cardiac function and remodeling. Moreover, fibrosis was less pronounced in the hearts of cKO mice after MI. Accordingly, CXCL12 Tg rats revealed impaired cardiac function post-MI accompanied by enhanced fibrosis. Furthermore, we observed decreased numbers of infiltrating Th1 cells in the hearts of cKO mice. Collectively, our findings demonstrate that cardiomyocyte derived CXCL12 is not involved in cardiac development but has adverse effects on the heart after injury via promotion of inflammation and fibrosis. KEY MESSAGES: * CXCL12 in cardiomyocytes is not involved in cardiac development. * CXCL12 deficiency in cardiomyocytes improves outcome of myocardial infarction. * CXCL12 overexpression in cardiomyocytes worsens outcome of myocardial infarction. * CXCL12 increases fibrosis and invasion of Th1 cells in the heart after infarction. PMID- 27251708 TI - The Contribution of Hearing and Hearing Loss to Balance Control. AB - This study investigated the hypothesis that a hearing 'map' of our surroundings is used to maintain balance control. We investigated the effects of sound on postural sway using centre of pressure analysis in 50 subjects with normal hearing, 28 with hearing loss and 19 with vestibular dysfunction. The acoustic environments utilized sound cues that were either present or absent. It was found that auditory cues are utilized by subjects with normal hearing to improve postural sway. The ability to utilize sound for postural control is diminished when there is a hearing loss, but this appears to be overcome by the use of a hearing aid. Patients with additional vestibular deficits exploit auditory cues to a greater degree, suggesting that sensory weighting to enhance the use of auditory cues may be applied when there is diminished sensory redundancy. PMID- 27251707 TI - Early growth response-1 in the pathogenesis of cardiovascular disease. AB - This article reviews the regulatory roles of the immediate-early gene product and prototypic zinc finger transcription factor, early growth response-1 in models of cardiovascular pathobiology, focusing on insights using microRNA, DNAzymes, small hairpin RNA, small interfering RNA, oligonucleotide decoy strategies and mice deficient in early growth response-1. PMID- 27251709 TI - How Does Sensor-Space Group Blind Source Separation Face Inter-individual Neuroanatomical Variability? Insights from a Simulation Study Based on the PALS B12 Atlas. AB - Because of volume conduction and inter-individual neuroanatomical variability, similar sources in different brains may lead to variable topographies. This represents a major limitation for sensor-space group level decomposition of electroencephalographic data, a technique which introduces potential biases when aggregating individual data. To which extent this impedes subsequent source separation and localization was quantified in the present study. To this end, several simulations using an atlas of human cerebral cortex that takes into account the variability of cortical morphology (Van Essen in NeuroImage 28:635 662, 2005) were performed. For each virtual subject (up to n = 160), the orientation and location of each single simulated dipole was randomly modified as a function of the variability of the cortical shape of a given point in the brain provided by the probabilistic atlas. The resulting activity was projected on the scalp, and topographical shifts were estimated. Then, different algorithms based on second order statistics (SOS) or higher order statistics were used to recover the simulated sources from sensor space information with group blind source separation (gBSS) procedures (based on UWSOBI or EFICA, respectively). As expected, the variability of orientation of the cortical surface across subjects was found to induce substantial variability in scalp potential maps, especially if the sources originate from the dorsolateral prefrontal cortex or the temporoparietal junction. These biases could be compensated for by increasing drastically the number of subjects included in the topographical analyses. By contrast, gBSS was found to be insensitive to inter-individual differences of neuroanatomy. Rather, the estimation of the spatial filters seems to be optimized for the population of interest. Thus, optimal performance of source separation and subsequent source localization did not require the inclusion of a large sample of subjects (n < 20), at least when applying SOS-based statistics that use source spectral diversity to identify and gather similar sources with variable location and orientation. The resulting conclusion that inter-individual neuroanatomical variability is not a major limitation to sensor-space gBSS methods provides boosting perspectives for this promising approach, especially for the detection and localization of task/population related neural sources. PMID- 27251710 TI - Change in Excitability of Corticospinal Pathway and GABA-Mediated Inhibitory Circuits of Primary Motor Cortex Induced by Contraction of Adjacent Hand Muscle. AB - The present study examined whether the excitability of the corticospinal pathway and the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the tonically contracting hand muscle are changed by tonic contraction of the adjacent hand muscle. The motor evoked potential (MEP) and cortical silent period (CSP) in the tonically contracting hand muscle were obtained while the adjacent hand muscle was either tonically contracting or at rest. The MEP and CSP of the first dorsal interosseous (FDI) muscle elicited across the scalp sites where the MEP is predominantly elicited in the FDI muscle were decreased by tonic contraction of the abductor digiti minimi (ADM) muscle. The centers of the area of the MEP and the duration of the CSP in the FDI muscle elicited across the sites where the MEP is predominantly elicited in the FDI muscle were lateral to those in the FDI muscle elicited across the sites where the MEP is elicited in both the FDI and ADM muscles. They were also lateral to those in the ADM muscle elicited either across the sites where the MEP is predominantly elicited in the ADM muscle, or across the sites where the MEP is elicited in both the FDI and ADM muscles. The decrease in the corticospinal excitability and the excitability of the GABA-mediated inhibitory circuits of the primary motor cortex that project onto the corticospinal neurons in the FDI muscle may be due either to (1) the interaction between the activity of the lateral area of the FDI representation and the descending drive to the ADM muscle, or (2) the decreased susceptibility of the primary motor area that predominantly projects onto the corticospinal neurons in the FDI muscle, which also plays a role in independent finger movement when both the FDI and ADM muscles act together as synergists. PMID- 27251712 TI - Impact of the plastidial stringent response in plant growth and stress responses. AB - The regulatory nucleotide guanosine 5'-diphosphate 3'-diphosphate (ppGpp), which was originally identified in Escherichia coli, controls the expression of a large gene set and many enzyme activities. The ppGpp-dependent control of cell activities is referred to as the stringent response. Recently, genes responsible for the synthesis and degradation of ppGpp have been identified not only in bacteria, but also in eukaryotes, including plants and animals, indicating that the stringent response is, unexpectedly, widely conserved. However, the exact function of the eukaryotic stringent response remains elusive. Here, we isolated an Arabidopsis mutant that overproduces ppGpp in chloroplasts. This mutant shows metabolite reduction, dwarf chloroplasts and significantly suppressed plastidial transcription and translation. Under nutrient-deficient conditions, the mutant shows more robust growth than the wild type. These results indicate that the ppGpp-dependent control of the organelle function is crucial for the systematic growth of host organisms. PMID- 27251711 TI - Corynebacterium pseudotuberculosis may be under anagenesis and biovar Equi forms biovar Ovis: a phylogenic inference from sequence and structural analysis. AB - BACKGROUND: Corynebacterium pseudotuberculosis can be classified into two biovars or biovars based on their nitrate-reducing ability. Strains isolated from sheep and goats show negative nitrate reduction and are termed biovar Ovis, while strains from horse and cattle exhibit positive nitrate reduction and are called biovar Equi. However, molecular evidence has not been established so far to understand this difference, specifically if these C. pseudotuberculosis strains are under an evolutionary process. RESULTS: The ERIC 1 + 2 Minimum-spanning tree from 367 strains of C. pseudotuberculosis showed that the great majority of biovar Ovis strains clustered together, but separately from biovar Equi strains that also clustered amongst themselves. Using evolutionarily conserved genes (rpoB, gapA, fusA, and rsmE) and their corresponding amino acid sequences, we analyzed the phylogenetic relationship among eighteen strains of C. pseudotuberculosis belonging to both biovars Ovis and Equi. Additionally, conserved point mutation based on structural variation analysis was also carried out to elucidate the genotype-phenotype correlations and speciation. We observed that the biovars are different at the molecular phylogenetic level and a probable anagenesis is occurring slowly within the species C. pseudotuberculosis. CONCLUSIONS: Taken together the results suggest that biovar Equi is forming the biovar Ovis. However, additional analyses using other genes and other bacterial strains are required to further support our anagenesis hypothesis in C. pseudotuberculosis. PMID- 27251714 TI - Genome sequencing: Long reads for a short plant. PMID- 27251713 TI - Accessibility controls selective degradation of photosystem II subunits by FtsH protease. AB - The oxygen-evolving photosystem II (PSII) complex located in chloroplasts and cyanobacteria is sensitive to light-induced damage(1) that unless repaired causes reduction in photosynthetic capacity and growth. Although a potential target for crop improvement, the mechanism of PSII repair remains unclear. The D1 reaction center protein is the main target for photodamage(2), with repair involving the selective degradation of the damaged protein by FtsH protease(3). How a single damaged PSII subunit is recognized for replacement is unknown. Here, we have tested the dark stability of PSII subunits in strains of the cyanobacterium Synechocystis PCC 6803 blocked at specific stages of assembly. We have found that when D1, which is normally shielded by the CP43 subunit, becomes exposed in a photochemically active PSII complex lacking CP43, it is selectively degraded by FtsH even in the dark. Removal of the CP47 subunit, which increases accessibility of FtsH to the D2 subunit, induced dark degradation of D2 at a faster rate than that of D1. In contrast, CP47 and CP43 are resistant to degradation in the dark. Our results indicate that protease accessibility induced by PSII disassembly is an important determinant in the selection of the D1 and D2 subunits to be degraded by FtsH. PMID- 27251715 TI - A polarly localized transporter for efficient manganese uptake in rice. AB - Manganese is an essential metal for plant growth. A number of transporters involved in the uptake of manganese from soils, and its translocation to the shoot, have been identified in Arabidopsis and rice. However, the transporter responsible for the radial transport of manganese out of root exodermis and endodermis cells and into the root stele remains unknown. Here, we show that metal tolerance protein 9 (MTP9), a member of the cation diffusion facilitator family, is a critical player in this process in rice (Oryza sativa). We find that MTP9 is mainly expressed in roots, and that the resulting protein is localized to the plasma membrane of exo- and endodermis cells, at the proximal side of these cell layers (opposite the manganese uptake transporter Nramp5, which is found at the distal side). We demonstrate that MTP9 has manganese transport activity by expression in proteoliposomes and yeast, and show that knockout of MTP9 in rice reduces manganese uptake and its translocation to shoots. We conclude that at least in rice MTP9 is required for manganese translocation to the root stele, and thereby manganese uptake. PMID- 27251716 TI - An intact light harvesting complex I antenna system is required for complete state transitions in Arabidopsis. AB - Efficient photosynthesis depends on maintaining balance between the rate of light driven electron transport occurring in photosystem I (PSI) and photosystem II (PSII), located in the chloroplast thylakoid membranes. Balance is achieved through a process of 'state transitions' that increases energy transfer towards PSI when PSII is overexcited (state II), and towards PSII when PSI is overexcited (state I). This is achieved through redox control of the phosphorylation state of light-harvesting antenna complex II (LHCII). PSI is served by both LHCII and four light-harvesting antenna complex I (LHCI) subunits, Lhca1, 2, 3 and 4. Here we demonstrate that despite unchanged levels of LHCII phosphorylation, absence of specific Lhca subunits reduces state transitions in Arabidopsis. The severest phenotype-observed in a mutant lacking Lhca4 (DeltaLhca4)-displayed a 69% reduction compared with the wild type. Yet, surprisingly, the amounts of the PSI LHCI-LHCII supercomplex isolated by blue native polyacrylamide gel electrophoresis (BN-PAGE) from digitonin-solubilized thylakoids were similar in the wild type and DeltaLhca mutants. Fluorescence excitation spectroscopy revealed that in the wild type this PSI-LHCI-LHCII supercomplex is supplemented by energy transfer from additional LHCII trimers in state II, whose binding is sensitive to digitonin, and which are absent in DeltaLhca4. The grana margins of the thylakoid membrane were found to be the primary site of interaction between this 'extra' LHCII and the PSI-LHCI-LHCII supercomplex in state II. The results suggest that the LHCI complexes mediate energetic interactions between LHCII and PSI in the intact membrane. PMID- 27251717 TI - Biome-scale nitrogen fixation strategies selected by climatic constraints on nitrogen cycle. AB - Dinitrogen fixation by plants (in symbiosis with root bacteria) is a major source of new nitrogen for land ecosystems(1). A long-standing puzzle(2) is that trees capable of nitrogen fixation are abundant in nitrogen-rich tropical forests, but absent or restricted to early successional stages in nitrogen-poor extra-tropical forests. This biome-scale pattern presents an evolutionary paradox(3), given that the physiological cost(4) of nitrogen fixation predicts the opposite pattern: fixers should be out-competed by non-fixers in nitrogen-rich conditions, but competitively superior in nitrogen-poor soils. Here we evaluate whether this paradox can be explained by the existence of different fixation strategies in tropical versus extra-tropical trees: facultative fixers (capable of downregulating fixation(5,6) by sanctioning mutualistic bacteria(7)) are common in the tropics, whereas obligate fixers (less able to downregulate fixation) dominate at higher latitudes. Using a game-theoretic approach, we assess the ecological and evolutionary conditions under which these fixation strategies emerge, and examine their dependence on climate-driven differences in the nitrogen cycle. We show that in the tropics, transient soil nitrogen deficits following disturbance and rapid tree growth favour a facultative strategy and the coexistence of fixers and non-fixers. In contrast, sustained nitrogen deficits following disturbance in extra-tropical forests favour an obligate fixation strategy, and cause fixers to be excluded in late successional stages. We conclude that biome-scale differences in the abundance of nitrogen fixers can be explained by the interaction between individual plant strategies and climatic constraints on the nitrogen cycle over evolutionary time. PMID- 27251719 TI - Auxin production couples endosperm development to fertilization. AB - In flowering plants, seed development is preceded by a double fertilization event, whereby two male sperm cells fuse with two female gametes: the egg and central cells. The fertilized egg cell will form the embryo, and the fertilized central cell will give rise to the triploid endosperm, whose function is to nourish and support the embryo. Even though the endosperm has an unparalleled role for human nutrition, the molecular bases for its development are yet to be understood. Our results reveal that increasing auxin levels after fertilization drive the replication of the central cell in Arabidopsis thaliana. Auxin is sufficient to trigger central cell division and is necessary for correct endosperm development, a process dependent on the MADS-box transcription factor AGL62 (AGAMOUS-LIKE 62). We propose that the epigenetic regulators of the Polycomb group (PcG) family block central cell division before fertilization by repressing the expression of auxin biosynthesis genes in the female gametophyte. PMID- 27251720 TI - Degradation of glyoxalase I in Brassica napus stigma leads to self incompatibility response. AB - Self-incompatibility (rejection of 'self'-pollen) is a reproductive barrier that allows hermaphroditic flowering plants to prevent inbreeding, to promote outcrossing and hybrid vigour. The self-incompatibility response in Brassica involves allele-specific interaction between the pollen small cysteine-rich, secreted protein ligand (SCR/SP11) and the stigmatic S-receptor kinase (SRK), which leads to the activation of the E3 ubiquitin ligase ARC1 (Armadillo repeat containing 1), resulting in proteasomal degradation of compatibility factors needed for successful pollination. Despite this, targets of ARC1 and the intracellular signalling network that is regulated by these targets, have remained elusive. Here we show that glyoxalase I (GLO1), an enzyme that is required for the detoxification of methylglyoxal (MG, a cytotoxic by-product of glycolysis), is a stigmatic compatibility factor required for pollination to occur and is targeted by the self-incompatibility system. Suppression of GLO1 was sufficient to reduce compatibility, and overexpression of GLO1 in self incompatible Brassica napus stigmas resulted in partial breakdown of the self incompatibility response. ARC1-mediated destruction of GLO1 after self pollination results in increased MG levels and a concomitant increase in MG modified proteins (including GLO1), which are efficiently targeted for destruction in the papillary cells, leading to pollen rejection. Our findings demonstrate the elegant nature of plants to use a metabolic by-product to regulate the self-incompatibility response. PMID- 27251722 TI - Development: Turning on endosperm in seeds. PMID- 27251723 TI - Chloroplast biology: Cost-benefit analysis. PMID- 27251721 TI - The wheat Sr50 gene reveals rich diversity at a cereal disease resistance locus. AB - We identify the wheat stem rust resistance gene Sr50 (using physical mapping, mutation and complementation) as homologous to barley Mla, encoding a coiled-coil nucleotide-binding leucine-rich repeat (CC-NB-LRR) protein. We show that Sr50 confers a unique resistance specificity different from Sr31 and other genes on rye chromosome 1RS, and is effective against the broadly virulent Ug99 race lineage. Extensive haplotype diversity at the rye Sr50 locus holds promise for mining effective resistance genes. PMID- 27251724 TI - Ethylene signalling: EIN2 dual targeting. PMID- 27251725 TI - Growing innovations for the bioeconomy. PMID- 27251726 TI - Deep influence of soil microbes. PMID- 27251728 TI - Grassland ecology: Rare plants and rainfall. PMID- 27251727 TI - Self-incompatibility: Avoiding inbreeding in Arabidopsis. PMID- 27251729 TI - Synthetic biology: Elegans control by auxin. PMID- 27251730 TI - Flower development: Sex lessons from cucumbers. PMID- 27251731 TI - Neglected tropical crops? PMID- 27251732 TI - Nitrogen fixation: Fixing evolution in global forests. PMID- 27251733 TI - Torsion, infarction, and rupture of a nongravid uterus: a complication of a large ovarian cyst. AB - Torsion of a nongravid uterus is rare, as most cases of uterine torsion occur during pregnancy. We report a case of a large ovarian cyst causing uterine torsion, infarction, and rupture. A 57-year-old woman presented with acute-onset abdominal pain and increasing abdominal girth over the past year. Contrast enhanced computed tomography (CT) demonstrated axial rotation and swirling of the uterus and the mesenteric fat, leading to a preoperative diagnosis of uterine torsion. Laparotomy confirmed that the uterine corpus had undergone a 180-degree axial rotation, and further revealed uterine wall infarction and rupture into the endometrium as well as partial decapitation of the uterus from the cervix. The swirled appearance of the uterus, radiologically similar to the "whirlpool sign" seen in bowel volvulus, is an important CT finding to recognize, especially in view of the risk of irreversible ischemic complications this uncommon entity may inflict on the uterus. PMID- 27251734 TI - Normal main portal vein diameter measured on CT is larger than the widely referenced upper limit of 13 mm. AB - OBJECTIVE: We determined mean main portal vein diameter in healthy patients evaluated with CT, compared this value to the "upper limit of normal" reported previously, and evaluated effects of age, sex, height, and BMI on portal vein diameter. MATERIALS AND METHODS: Our cohort of healthy patients underwent abdominal CT as potential renal donors. We excluded patients with evidence of liver or severe cardiac disease. We recorded patients' age, sex, height, weight, and BMI. Patients' main portal vein diameters were measured by fellowship-trained abdominal imagers on non-contrast and post-contrast images in axial and coronal projections at a defined location. A general linear mixed model was used for analysis. RESULTS: 191 patients with 679 main portal vein measurements were included in the analysis. Mean main portal vein diameter was 15.5 +/- 1.9 mm; this value was significantly different from the upper limit of normal of 13 mm commonly referenced in the literature (95% CI: 2.22-2.69 mm higher, p < 0.0001). Portal vein diameter does not vary significantly when measured on axial vs. coronal images. On average, post-contrast main portal veins were 0.56 mm larger compared to non-contrast, (95% CI: 0.40-0.71 mm, p < 0.0071). Patient height and BMI are positively correlated with MPV diameter. CONCLUSIONS: Normal mean portal vein diameter measured on CT was significantly larger (mean 15.5 mm) than the accepted upper limit of 13 mm. Contrast-enhanced main portal veins are significantly larger (0.56 mm) than unenhanced. Sex, height, and BMI significantly affect main portal vein diameter. PMID- 27251735 TI - Massive splenic infarction and splenic venous thrombosis observed in a patient with acute splenic syndrome of sickle cell traits on contrast-enhanced thin-slice computed tomography. AB - We report a case of splenic infarction in a patient with sickle cell traits (SCT), focusing on the computed tomography (CT) findings. The patient was an African-American man in his twenties with no past medical history who experienced sudden left upper quadrant pain while climbing a mountain (over 3000 m above sea level). Dynamic contrast-enhanced CT revealed massive non-segmental splenic infarction accompanied with nodule-like preserved splenic tissue. The region of splenic infarction did not coincide with the arterial vascular territory and differed from the features of infarction caused by large arterial embolism. In addition, thrombotic occlusion of the distal splenic vein was depicted on plain and contrast-enhanced thin-slice CT images. Early-phase contrast-enhanced images also showed inhomogeneous enhancement of the hepatic parenchyma. The patient's symptoms improved with conservative therapy. A hemoglobin electrophoresis test confirmed the diagnosis of SCT. SCT is usually asymptomatic, but hypoxic environments may induce acute splenic syndrome, which is commonly manifested as splenic infarction. We observed splenic venous thrombosis and inhomogeneous hepatic parenchymal enhancement in addition to a huge splenic infarction in our patient. To the best of our knowledge, this is the first report describing the specific imaging findings, particularly splenic venous thrombosis and inhomogeneous hepatic parenchymal enhancement, of acute splenic syndrome in a patient with previously undiagnosed SCT. These findings demonstrate the pathophysiology of SCT, and may help with the diagnosis of this disease. PMID- 27251736 TI - The imaging findings of typical and atypical genital and gynecologic infections. AB - Genital and gynecologic infections are common medical problems, affecting millions of women worldwide. The spectrum of these infections extends from the labia, including processes such as necrotizing fasciitis and anogenital warts, to the upper reproductive tracts in conditions including endometritis and pelvic inflammatory disease. Although often a clinical diagnosis, the radiologist plays an important role in determining the etiology of acute abdominal and pelvic pain as well as facilitating the diagnosis for cases which are not clinically straightforward. Imaging also plays an important role in assessing the complications and sequelae of these conditions, including infertility, chronic abdominal and pelvic pain, and pelvic adhesions. Familiarity with the appearances of these infections, their complications, and their potential mimics on sonography, computed tomography, magnetic resonance imaging, and hysterosalpingography is important for timely diagnosis and optimal clinical outcomes. PMID- 27251737 TI - CT gastrography for volumetric measurement of remnant stomach after distal gastrectomy: a feasibility study. AB - PURPOSE: To evaluate the feasibility of post-operative CT gastrography for volumetry of the remnant stomach in gastric cancer patients treated with distal gastrectomy. METHODS: CT gastrography was performed with oral administration of effervescent granules in 35 gastric cancer patients who underwent distal gastrectomy. Two readers independently rated the degree of gastric distension on a four-point scale, one (near-total collapse) to four (well distended) and measured the volume of remnant stomach using either 3D or 2D volumetry. The inter volumetry agreements between the 2D and 3D methods and the interobserver agreements between readers 1 and 2 were assessed by intraclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: The mean score of gastric distension was 3.4 +/- 0.6 points and 3.4 +/- 0.7 points from readers 1 and 2, respectively. We regarded CT images scored with 3-4 points as a technical success for reliable CT volumetry, which achieved a rate of 91.4% (32/35). For the inter volumetry agreements between 3D and 2D volumetry, the ICCs were 0.9778 and 0.9814 from readers 1 and 2, respectively. The interobserver agreement between readers 1 and 2 was also excellent, with ICCs of 0.9961 and 0.9876 for 2D and 3D volumetry, respectively. On Bland-Altman plots, the means of differences between any pairs of volumetry measurements ranged from -31.1 to 3.2 cm(3), which may be an acceptable range of measurement variability. CONCLUSIONS: Post-operative CT gastrography is feasible in patients treated with distal gastrectomy. Both 2D and 3D volumetry methods are comparable in measuring the remnant stomach volume. PMID- 27251738 TI - [Connections between sleep and Alzheimer's disease : Insomnia, amnesia and amyloid]. AB - Sleep plays an essential role in memory consolidation. Although sleep problems are common in Alzheimer's disease, they are not usually thought to be key features of the disease; however, new experimental research has shown that sleep disturbances not only occur before the onset of typical cognitive deficits but are also associated with the pathogenesis of Alzheimer's disease and may have a decisive influence on the symptoms and course. Thus, sleep disturbances may be potentially modifiable risk factors for Alzheimer's disease that deserve more attention in research, diagnostics and treatment. PMID- 27251739 TI - [System-immanent incentives in the remuneration for psychiatry and psychosomatics : Analysis exemplified by treatment of alcohol-related disorders]. AB - BACKGROUND: The German fixed rate remuneration system in psychiatry and psychosomatics (PEPP) has been criticized by many specialty associations because negative effects on mental healthcare are expected through economic incentives. OBJECTIVE: Through analysis of performance data in the treatment of alcohol dependency at the Evangelical Hospital Bielefeld (Evangelisches Krankenhaus Bielefeld, EvKB) from 2014 and various simulations, the incentives of the PEPP (version 2015) were analyzed and its potential impact on patient care was evaluated. METHODS: Groups of cases were created based on the clinical data. Various parameters were evaluated, such as duration of treatment, PEPP coding, loss of income by merging cases and case remuneration. Additionally, changes in the duration of treatment, the intensity of treatment and the intensity of care were simulated. RESULTS: In the simulations a reduction in the duration of treatment by 16.1 % led to additional revenues of 1.9 % per treatment day. The calculated additional costs of 1:1 care and intensive nursing care were not completely covered by the additional revenues, whereas psychotherapeutic inpatient treatment programs showed positive profit contributions. Complicated cases with increased merging of cases showed lower revenues but with above average expenditure of efforts. CONCLUSION: The current version of the PEPP leads to misdirected incentives in patient care. This is caused, for example, by the fact that higher profit contributions can be realized in some patient groups and intensive nursing care of patients is insufficiently represented. It is not clear whether these incentives will persist or can be compensated in subsequent versions of the system. PMID- 27251740 TI - Concurrent Loss of Heterozygosity and Mosaic Deletion of 12p13.32pter. AB - Deletions in the short arm of chromosome 12 are the rarest subtelomeric imbalances. Less than 20 patients have been reported to date, and their microdeletions were identified either by FISH or array-CGH without SNP data. Here, we report a patient with a 12p13.32pter mosaic deletion detected by chromosome microarray analysis with loss of heterozygosity (LOH) of the deleted segment in addition to the adjacent distal segment. LOH is indicative of a complex rearrangement, suggestive of mitotic microhomology-mediated break-induced replication. PMID- 27251741 TI - The HSP90 inhibitor, 17AAG, protects the intestinal stem cell niche and inhibits graft versus host disease development. PMID- 27251742 TI - Regulation of osteosarcoma cell lung metastasis by the c-Fos/AP-1 target FGFR1. PMID- 27251743 TI - Electrocardiograms in African Americans and Non-African Americans Presenting with Takotsubo Syndrome. PMID- 27251744 TI - [Age is no protection against technology?!]. PMID- 27251745 TI - [Risk-benefit profile of testosterone treatment for older men]. PMID- 27251746 TI - Stem Cells for Neonatal Brain Disorders. AB - Despite recent advances in neonatal intensive care medicine, neonatal brain injury resulting from intraventricular hemorrhage or hypoxic-ischemic encephalopathy remains a major cause of neonatal mortality and neurologic morbidities in survivors. Several studies have indicated that stem cell therapy is a promising novel therapy for neonatal brain injury resulting from these disorders. This review summarizes recent advances in stem cell research for treating neonatal brain injury due to intraventricular hemorrhage or hypoxic ischemic encephalopathy with a particular focus on preclinical data, covering important issues for clinical translation such as optimal cell type, route, dose and timing of stem cell therapy, and translation of these preclinical results into a clinical trial. PMID- 27251747 TI - Genome-scale metabolic models as platforms for strain design and biological discovery. AB - Genome-scale metabolic models (GEMs) have been developed and used in guiding systems' metabolic engineering strategies for strain design and development. This strategy has been used in fermentative production of bio-based industrial chemicals and fuels from alternative carbon sources. However, computer-aided hypotheses building using established algorithms and software platforms for biological discovery can be integrated into the pipeline for strain design strategy to create superior strains of microorganisms for targeted biosynthetic goals. Here, I described an integrated workflow strategy using GEMs for strain design and biological discovery. Specific case studies of strain design and biological discovery using Escherichia coli genome-scale model are presented and discussed. The integrated workflow presented herein, when applied carefully would help guide future design strategies for high-performance microbial strains that have existing and forthcoming genome-scale metabolic models. PMID- 27251748 TI - Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment. AB - Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation. This transcription factor also directly or indirectly targets and controls the expression of some early and late adipogenic regulators (i.e. Zfp423, Zfp467, KLF15, C/EBPdelta, C/EBPalpha and PPARgamma). We further identified that Bcl6 transactivated the signal transducers and activators of transcription 1 (STAT1), which was determined as a required factor for adipogenesis. Moreover, overexpression of STAT1 rescued the impairment of adipogenic commitment and differentiation induced by Bcl6 knockdown in C3H10T1/2 cells, thereby confirming that STAT1 is a downstream direct target of Bcl6. This study identifies Bcl6 as a positive transcriptional regulator of early adipose commitment. PMID- 27251749 TI - Rapid Resorbable Sutures Are a Favourable Alternative to Non-resorbable Sutures in Closing Transcolumellar Incision in Rhinoplasty. AB - BACKGROUND: The open approach using inverted-V incisions has gained popularity in both primary and revision rhinoplasty during the last years. The risk of a disturbing columellar scar has been shown to be very low when meticulously closed. However, the suture extractions are usually painful and time consuming. OBJECTIVES: To investigate if rapid resorbable sutures could replace non resorbable sutures in nasal transcolumellar incisions. The present study compared (1) patient discomfort, (2) scarring and (3) risk for postoperative infection. MATERIALS AND METHODS: A total of 58 consecutive patients subjected to open rhinoplasty by the same surgeon using midcolumellar inverted-V incisions were investigated retrospectively. Forty-one (71 %) were eligible and investigated, of whom 27 (65 %) were of Middle Eastern descent and the rest Caucasians from Northern Europe. The first 21 patients were sutured with non-resorbable suture material polypropylene (PP) (Prolene((r)) 5/0; Ethicon Inc.) and the subsequent 20 patients with a rapidly resorbable suture material, the 5/0 irradiated Polygalactic acid (PGA); (Vicryl Rapide((r)) 5/0; Ethicon Inc.). Discomfort from the suture extraction of the PP sutures was compared to trimming of the PGA sutures at the skin surface 1 week postoperatively, and visibility of the columellar scars was evaluated by the patients themselves on a self-report questionnaire. This was done prior to the investigation and postoperative photography at the follow-up visit a minimum of 6 months postoperatively. The postoperative photographs were then assessed by 20 rhinoplasty surgeons independently, using the same questionnaire. RESULTS: Trimming of the PGA sutures caused significantly less discomfort than the extraction of PP sutures (p <= 0.01), of which 6 (29 %) found the suture extraction very painful. Overall, 40/41 (98 %) found their scars non-disturbing. Moreover, 17/21 (81 %) of the patients sutured with PP and 18/20 (90 %) of the patients sutured with PGA considered their scars to be invisible or almost invisible. The corresponding assessments from the observers were 16/21 (76 %) and 16/20 (80 %), respectively. No postoperative infection was found in any group. CONCLUSION: Suturing inverted-V transcolumellar incisions with rapid resorbable sutures caused significantly less discomfort but no difference in scarring compared to non-resorbable sutures as evaluated by patients and observers. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27251750 TI - Management of Breast Deformity After Removal of Injectable Polyacrylamide Hydrogel: Retrospective Study of 200 Cases for 7 Years. AB - BACKGROUND: Polyacrylamide hydrogel (PAAG), once used as an injection for breast augmentation, has been banned in the medical field for cosmetic purposes for more than 10 years in China. But a large number of breasts have characteristic deformities due to the gel's feature of erosion. Our aim is to explore a retrospective study on PAAG's long-term effects on women, ensuing breast deformity and the strategy for breast plasticity after removing the gel in our center from 2007 to 2014. METHODS: From 2007 to 2014, 200 patients, whose breasts were injected with PAAG, underwent the operation to remove the injectable material. Complications were summarized. Ultrasound or MRI was performed before the operation to disclose the general distribution of the gel and the muscle and gland infiltration. According to the gel distribution, muscle and gland infiltration, infection, gel residue, and other factors, the patients were treated, respectively, with or without prosthesis implantation surgery after the removal of the gel. According to the decision about whether or when to undergo prosthesis implantation, the patients were classified into three types: group I prosthesis implantation at the first stage, group II-prosthesis implantation at the second stage, and group III-only removing the material without prosthesis implantation. The scores of the BREAST-Q program were used to evaluate the preoperative and postoperative differences. RESULTS: Seventy-seven patients underwent prosthesis implantation at the first stage and 61 patients were operated on by placing the prosthesis at the second stage. A total of 62 patients only underwent the PAAG removal operation. By BREAST-Q evaluation, changes are summarized in Tables 1, 2, and 3 between mean preoperative scores and mean postoperative scores through categories of satisfaction with appearance of breasts, psychosocial wellbeing, sexual wellbeing, and physical wellbeing, in which all categories were presented with statistical significance (p < 0.001). Table 1 Patient demographics General patient data Number Number of patients 200 Age range 25-48 Follow-up period 6-12 months Injection material Domestic material 84 (42 %) Imported material 93 (46.5 %) Domestic + imported 23 (11.5 %) Injection site Regular hospital 47 (23.5 %) Clinics 153 (76.5 %) Complication Inflammation 10 (2 %) Pain 75 (37.5 %) Induration 155 (77.5 %) Shift 50 (25 %) Deformation 17 (8.5 %) Bilateral asymmetry 48 (24 %) Deposition milk 2 (1 %) Psychological fear 150 (75 %) Systemic symptoms 34 (17 %) Single complication 25 (16.97 %) Two or more complications 160 (80 %) Preoperative aspiration 48 (24 %) Table 2 Group I-changes in mean preoperative scores and mean postoperative scores Category Preoperatively (n = 77) Postoperatively (n = 77) p Satisfaction with appearance of breasts 18.8 +/- 16.2 81.6 +/- 13.1 <0.001 Psychosocial wellbeing 39.5 +/- 20.2 84.5 +/- 19.3 <0.001 Sexual wellbeing 38.7 +/- 23.1 77.2 +/- 20.5 <0.001 Physical wellbeing 42.4 +/- 16.3 81.7 +/- 10.5 <0.001 Table 3 Group II-changes in mean preoperative scores and mean postoperative scores Category Preoperatively (n = 61) Postoperatively (n = 61) p Satisfaction with appearance of breasts 19.6 +/- 15.3 82.5 +/- 11.1 <0.001 Psychosocial wellbeing 38.9 +/- 19.3 83.6 +/- 20.1 <0.001 Sexual wellbeing 37.6 +/- 22.4 79.3 +/- 20.4 <0.001 Physical wellbeing 41.3 +/- 15.1 82.2 +/- 9.9 <0.001 CONCLUSIONS: Timely removal is critical for women who have received the PAAG removal operation. However, the surgery may destroy the shape of the breast. It is recommended that preoperative communication and local tissue condition are guidelines for surgeons to choose conservative or aggressive surgery. A balance must be maintained between removing the gel as much as possible and retaining soft tissue to reshape breasts. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27251751 TI - Eumorphic Plastic Surgery: Expectation Versus Satisfaction in Body Dysmorphic Disorder. AB - BACKGROUND: Eumorphic Plastic Surgery aims at improving the severe psychosocial pain caused by a deformity. Dysmorphopathology is an increasingly relevant problem facing the plastic surgeon. OBJECTIVE: The aim of this study is to describe the perioperative questionnaires created by the senior author and to present a cohort of plastic surgery patients suffering from dysmorphopathies. These patients were prospectively followed and evaluated with the proposed questionnaires through their surgical pathway to explore the degree of satisfaction or disappointment compared to expectations. METHODS: All candidates for plastic surgery procedures between April 2011 and June 2013 were included in the study. Preoperatively, all patients completed the Patient Expectation Questionnaire (E-pgm). Twelve months postoperatively, they completed the Patient Satisfaction Questionnaire (S-pgm). The E-pgm and S-pgm were compared to evaluate the consistency between the patient's preoperative expectations and postoperative evaluations. RESULTS: A total of 158 patients were included in the study. Out of them, 79 % experienced an improvement or no variation between preoperative expectations and postoperative satisfaction. With regard to the motivation for undergoing surgery, 91 % showed that the surgical procedure met the motivation. An overall positive perioperative change in life was experienced by 93 % of patients. CONCLUSIONS: The E-pgm questionnaire proved to be a valid and reliable tool for the selection of suitable candidates for surgery and for identification of dysmorphophobic patients. Enhancing the doctor-patient relationship and communication can reduce ambiguity and avoid troublesome misunderstandings, litigation and other legal implications. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27251752 TI - Interaction in planning vocalizations and grasping. AB - Previous studies have shown a congruency effect between manual grasping and syllable articulation. For instance, a power grip is associated with syllables whose articulation involves the tongue body and/or large mouth aperture ([kalpha]) whereas a precision grip is associated with articulations that involve the tongue tip and/or small mouth aperture ([ti]). Previously, this effect has been observed in manual reaction times. The primary aim of the current study was to investigate whether this congruency effect also takes place in vocal responses and to investigate involvement of action selection processes in the effect. The congruency effect was found in vocal and manual responses regardless of whether or not the syllable or grip was known a priori, suggesting that the effect operates with minimal or absent action selection processes. In addition, the effect was observed in vocal responses even when the grip was only prepared but not performed, suggesting that merely planning a grip response primes the corresponding articulatory response. These results support the view that articulation and grasping are processed in a partially overlapping network. PMID- 27251753 TI - Limitations of videolaryngoscopy. PMID- 27251754 TI - Clinical and immunological analysis of measles patients admitted to a Beijing hospital in 2014 during an outbreak in China. AB - At the end of 2013, China reported a countrywide outbreak of measles. From January to May 2014, we investigated the clinical and immunological features of the cases of the outbreak admitted to our hospital. In this study, all 112 inpatients with clinically diagnosed measles were recruited from the 302 Military Hospital of China. The virus was isolated from throat swabs from these patients, and cytokine profiles were examined. By detecting the measles virus of 30 of the 112 patients, we found that this measles outbreak was of the H1 genotype, which is the major strain in China. The rates of complications, specifically pneumonia and liver injury, differed significantly in patients aged 18 years: pneumonia was more common in children, while liver injury was more common in adults. Pneumonia was a significant independent risk factor affecting measles duration. Compared to healthy subjects, measles patients had fewer CD4+IL-17+, CD4+IFN-gamma +, and CD8+IFN-gamma + cells in both the acute and recovery phases. In contrast, measles patients in the acute phase had more CD8+IL-22+ cells than those in recovery or healthy subjects. We recommend that future studies focus on the age-related distribution of pneumonia and liver injury as measles-related complications as well as the association between immunological markers and measles prognosis. PMID- 27251755 TI - Morphological Transformation between Nanocoils and Nanoribbons via Defragmentation Structural Rearrangement or Fragmentation-recombination Mechanism. AB - Kinetic control over the assembly pathways towards novel metastable functional materials or far-from-equilibrium systems has been much less studied compared to the thermodynamic equilibrium self-assembly. Herein, we report the distinct morphological transformation between nanocoils and nanoribbons in the self assembly of unsymmetric perylene diimide (PDI) molecules. We demonstrate that the morphological transformation of the kinetically trapped assemblies into the thermodynamically stable forms proceeds via two distinct mechanisms, i.e., a direct structural rearrangement (molecule 1 or 2) and a fragmentation recombination mechanism (molecule 4), respectively. The subtle interplay of the steric hindrance of the bulky substituents and the flexibility of the linker structure between the bulky moiety and the perylene core was demonstrated to enable the effective modulation of the energetic landscape of the assemblies and thus modulation of the assembly pathways. Herein, our work presents a new approach to control the self-assembly pathways and thereby can be used to achieve novel far-from-equilibrium systems. PMID- 27251756 TI - A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells. AB - BACKGROUND: Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells' viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris containing immune-activatory danger associated molecular patterns, and due to the increased quantities of degraded proteins and RNA. RESULTS: Over 40 resected BTs and non-tumorous brain tissue samples were dissociated into single cells by mechanical dissociation or by mechanical and enzymatic dissociation. The quality of dissociation was compared for all frequently used dissociation enzymes (collagenase, DNase, hyaluronidase, papain, dispase) and for neutral protease (NP) from Clostridium histolyticum. Single-cell dissociated cell mixtures were evaluated for cellular viability and for the cell mixture dissociation quality. Dissociation quality was graded by the quantity of subcellular debris, non-dissociated cell clumps, and DNA released from dead cells. Of all enzymes or enzyme combinations examined, NP (an enzyme previously not evaluated on brain tissues) produced dissociated cell mixtures with the highest mean cellular viability: 93 % in gliomas, 85 % in brain metastases, and 89 % in non-tumorous brain tissue. NP also produced cell mixtures with significantly less cellular debris than other enzymes tested. Dissociation using NP was non-aggressive over time-no changes in cell viability or dissociation quality were found when comparing 2-h dissociation at 37 degrees C to overnight dissociation at ambient temperature. CONCLUSIONS: The use of NP allows for the most effective dissociation of viable single cells from human BTs or brain tissue. Its non-aggressive dissociative capacity may enable ambient-temperature shipping of tumor pieces in multi-center clinical trials, meanwhile being dissociated. As clinical grade NP is commercially available it can be easily integrated into cell-therapy clinical trials in neuro-oncology. The high quality viable cells produced may enable investigators to conduct more consistent research by avoiding the experimental artifacts associated with the presence dead cells or cellular debris. PMID- 27251757 TI - Pharmacokinetics and the effect of heat on intraperitoneal pemetrexed using a murine model. AB - BACKGROUND: Pemetrexed is a systemic chemotherapeutic agent used in the treatment of malignant mesothelioma. This drug represents a potentially promising intraperitoneal (IP) agent to use for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal mesothelioma. However, this has yet to be supported by preclinical studies. Therefore, we aimed to study the effect of pemetrexed dose and perfusion temperature on the resultant pemetrexed concentration in 3 different compartments (systemic circulation, portal circulation and peritoneal tissues) using a murine model. METHODS: Under general anesthesia, 29 Sprague-Dawley rats were submitted to 3 different doses of IP pemetrexed (500, 1000 and 1500 mg/m2) combined with 3 different perfusion temperatures (37, 40 and 43 degrees C) for a total duration of 25 min. At the end of perfusion, samples in different compartments (systemic circulation, portal circulation and peritoneum) were harvested and concentrations of pemetrexed were measured using high performance liquid chromatography. RESULTS: With increasing dose of IP pemetrexed, higher concentrations were measured in the 3 compartments tested. In peritoneal cells, the difference between IP doses of 500 and 1000 mg/m2 (2.03 vs. 19.17 MUg/g, p < 0.001) was greater than the difference between 1000 and 1500 mg/m2 (19.17 vs. 22.80 MUg/g, p = 0.027). When the perfusion temperature increased, we observed a proportional rise of pemetrexed concentration in both the portal and systemic compartments; while in the peritoneal cells, the pemetrexed concentration increased up to 40 degrees C, after which it plateaued. CONCLUSION: Both heat and increasing doses of IP pemetrexed enhance peritoneal cell concentration of pemetrexed. However, for temperatures above 40 degrees C, pemetrexed concentration reached a plateau in peritoneal cells. Systemic and portal concentrations increased proportionally with both increasing temperatures and IP doses. We believe these results should be taken into consideration for the design of an eventual clinical study in humans. PMID- 27251760 TI - Initialized decadal prediction for transition to positive phase of the Interdecadal Pacific Oscillation. AB - The negative phase of the Interdecadal Pacific Oscillation (IPO), a dominant mode of multi-decadal variability of sea surface temperatures (SSTs) in the Pacific, contributed to the reduced rate of global surface temperature warming in the early 2000s. A proposed mechanism for IPO multidecadal variability indicates that the presence of decadal timescale upper ocean heat content in the off-equatorial western tropical Pacific can provide conditions for an interannual El Nino/Southern Oscillation event to trigger a transition of tropical Pacific SSTs to the opposite IPO phase. Here we show that a decadal prediction initialized in 2013 simulates predicted Nino3.4 SSTs that have qualitatively tracked the observations through 2015. The year three to seven average prediction (2015-2019) from the 2013 initial state shows a transition to the positive phase of the IPO from the previous negative phase and a resumption of larger rates of global warming over the 2013-2022 period consistent with a positive IPO phase. PMID- 27251758 TI - The co-chaperone Cdc37 regulates the rabies virus phosphoprotein stability by targeting to Hsp90AA1 machinery. AB - Cdc37, as a kinase-specific co-chaperone of the chaperone Hsp90AA1 (Hsp90), actively aids with the maturation, stabilization and activation of the cellular or viral kinase/kinase-like targets. Phosphoprotein (P) of rabies virus (RABV) is a multifunctional, non-kinase protein involved in interferon antagonism, viral transcription and replication. Here, we demonstrated that the RABV non-kinase P is chaperoned by Cdc37 and Hsp90 during infection. We found that Cdc37 and Hsp90 affect the RABV life cycle directly. Activity inhibition and knockdown of Cdc37 and Hsp90 increased the instability of the viral P protein. Overexpression of Cdc37 and Hsp90 maintained P's stability but did not increase the yield of infectious RABV virions. We further demonstrated that the non-enzymatic polymerase cofactor P protein of all the genotypes of lyssaviruses is a target of the Cdc37/Hsp90 complex. Cdc37, phosphorylated or unphosphorylated on Ser13, aids the P protein to load onto the Hsp90 machinery, with or without Cdc37 binding to Hsp90. However, the interaction between Cdc37 and Hsp90 appears to have additional allosteric regulation of the conformational switch of Hsp90. Our study highlighted a novel mechanism in which Cdc37/Hsp90 chaperones a non-kinase target, which has significant implications for designing therapeutic targets against Rabies. PMID- 27251759 TI - Racial differences in head and neck squamous cell carcinomas among non-Hispanic black and white males identified through the National Cancer Database (1998 2012). AB - PURPOSE: Head and neck squamous cell carcinoma (HNSCC) incidence is increasing, and evidence suggests survival disparities between non-Hispanic (nH) black and white males. However, temporal changes in HNSCCs and factors contributing to survival differences have not been examined at the national level. METHODS: National Cancer Database (NCDB) cases were used to evaluate temporal trends in HNSCC anatomical sites and site groupings (i.e., oral cavity, oropharyngeal, non oropharyngeal), and to estimate incidence ratios (IRs) comparing nH black and white males in demographic and clinical characteristics. RESULTS: Between 1998 and 2012, 18,443 (11 %) nH black males and 145,611 (89 %) nH white males were diagnosed with HNSCCs. Cases rose from 9094 diagnosed in 1998 to 13,838 in 2012, driven by increases in oropharyngeal tumors, particularly tumors of the tonsil and tongue. Annual percent changes in nH black males and nH white males were 1.93 and 3.17, respectively. Additionally, nH black males had higher incidence of the more aggressive non-oropharyngeal tumors (p < .0001) and distant-stage tumors (76 vs. 64 %, p < .0001). However, nH white males had higher incidence of high-risk HPV types (IRs range from 1.68, 95 % CI 1.50-1.88 in oropharyngeal tumors to 3.03, 95 % CI 1.11-8.25 in non-oropharyngeal tumors). CONCLUSIONS: Incidence of oropharyngeal tumors has risen in both nH black and white males. However, nH white males have higher incidence of HPV, and nH black males have higher incidence of more aggressive and advanced HNSCCs. Racial differences in clinical characteristics associated with poorer survival exist, and future studies should determine factors associated with these differences. PMID- 27251761 TI - Apparent Mineralocorticoid Excess Syndrome: A Case of Resistant Hypertension From Licorice Tea Consumption. PMID- 27251762 TI - Rethinking spontaneous giving: Extreme time pressure and ego-depletion favor self regarding reactions. AB - Previous experimental studies suggest that cooperation in one-shot anonymous interactions is, on average, spontaneous, rather than calculative. To explain this finding, it has been proposed that people internalize cooperative heuristics in their everyday life and bring them as intuitive strategies in new and atypical situations. Yet, these studies have important limitations, as they promote intuitive responses using weak time pressure or conceptual priming of intuition. Since these manipulations do not deplete participants' ability to reason completely, it remains unclear whether cooperative heuristics are really automatic or they emerge after a small, but positive, amount of deliberation. Consistent with the latter hypothesis, we report two experiments demonstrating that spontaneous reactions in one-shot anonymous interactions tend to be egoistic. In doing so, our findings shed further light on the cognitive underpinnings of cooperation, as they suggest that cooperation in one-shot interactions is not automatic, but appears only at later stages of reasoning. PMID- 27251764 TI - Intramolecular Electron Transfers Thwart Bistability in a Pentanuclear Iron Complex. AB - With the intention to investigate the redox properties of polynuclear complexes as previously reported for the pentamanganese complex [{Mn(II)(MU bpp)3}2Mn(III)Mn(II)2(MU3-O)](3+) (2(3+)), we focused on the analogous pentairon complex that was previously isolated as all-ferrous. As Masaoka and co-workers recently published, aerobic synthesis leads to the [{Fe(II)(MU bpp)3}2Fe(III)Fe(II)2(MU3-O)](3+) complex (1(3+)). This species exhibits in acetonitrile solution four reversible one-electron oxidation waves. Accordingly, the three oxidized species 1(4+), 1(5+), and 1(6+) with a 3Fe(II)2Fe(III), 2Fe(II)3Fe(III), and 1Fe(II)4Fe(III) composition, respectively, were generated by bulk electrolysis and isolated. Mossbauer spectroscopy allowed us to determine the spin states of all the iron ions and to unambiguously locate the sites of the successive oxidations. They all occur in the MU3-oxo core except for the 1(4+) to 1(5+) process that presents a striking electronic rearrangement, with both metals in axial position being oxidized while the core is reduced to the [Fe(III)Fe(II)2(MU3-O)](5+) oxidation level. This strongly differs from the redox behavior of the Mn5 system. The origin of this electronic switch is discussed. PMID- 27251763 TI - Finding Web-Based Anxiety Interventions on the World Wide Web: A Scoping Review. AB - BACKGROUND: One relatively new and increasingly popular approach of increasing access to treatment is Web-based intervention programs. The advantage of Web based approaches is the accessibility, affordability, and anonymity of potentially evidence-based treatment. Despite much research evidence on the effectiveness of Web-based interventions for anxiety found in the literature, little is known about what is publically available for potential consumers on the Web. OBJECTIVE: Our aim was to explore what a consumer searching the Web for Web based intervention options for anxiety-related issues might find. The objectives were to identify currently publically available Web-based intervention programs for anxiety and to synthesize and review these in terms of (1) website characteristics such as credibility and accessibility; (2) intervention program characteristics such as intervention focus, design, and presentation modes; (3) therapeutic elements employed; and (4) published evidence of efficacy. METHODS: Web keyword searches were carried out on three major search engines (Google, Bing, and Yahoo-UK platforms). For each search, the first 25 hyperlinks were screened for eligible programs. Included were programs that were designed for anxiety symptoms, currently publically accessible on the Web, had an online component, a structured treatment plan, and were available in English. Data were extracted for website characteristics, program characteristics, therapeutic characteristics, as well as empirical evidence. Programs were also evaluated using a 16-point rating tool. RESULTS: The search resulted in 34 programs that were eligible for review. A wide variety of programs for anxiety, including specific anxiety disorders, and anxiety in combination with stress, depression, or anger were identified and based predominantly on cognitive behavioral therapy techniques. The majority of websites were rated as credible, secure, and free of advertisement. The majority required users to register and/or to pay a program access fee. Half of the programs offered some form of paid therapist or professional support. Programs varied in treatment length and number of modules and employed a variety of presentation modes. Relatively few programs had published research evidence of the intervention's efficacy. CONCLUSIONS: This review represents a snapshot of available Web-based intervention programs for anxiety that could be found by consumers in March 2015. The consumer is confronted with a diversity of programs, which makes it difficult to identify an appropriate program. Limited reports and existence of empirical evidence for efficacy make it even more challenging to identify credible and reliable programs. This highlights the need for consistent guidelines and standards on developing, providing, and evaluating Web-based interventions and platforms with reliable up-to-date information for professionals and consumers about the characteristics, quality, and accessibility of Web-based interventions. PMID- 27251765 TI - Metabonomic analysis of the protective effect of quercetin on the toxicity induced by mixture of organophosphate pesticides in rat urine. AB - The present study aims to investigate the protective effect of quercetin against the joint toxic action induced by the mixture of four organophosphate pesticides (mixture-OPs) (dimethoate, acephate, dichlorvos, and phorate) at their corresponding no observed adverse effect level (NOAEL) using metabonomics. Rats were randomly divided into control, quercetin-treated, mixture-OPs-treated, and quercetin plus mixture-OPs-treated groups. Mixture-OPs and quercetin were given to the rats daily through drinking water and intragastric administration, respectively, for 90 days. The metabonomic profiles of rat urine were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC/MS). The 14 metabolites significantly changed in the treatment groups compared with the control group, including the biomarkers of OPs exposure (dimethylphosphate, dimethyldithiophosphate, diethylphosphate) and the metabolites of quercetin (quercetin and isorhamnetina). The intensities of gentisic acid, creatinine, suberic acid, hippuric acid, uric acid, and citric acid significantly decreased, whereas the intensities of 7-methylguanine, estrone sulfate, and cholic acid significantly increased, in the mixture-OPs-treated group compared with the control group ( p < 0.01). The variation tendency of the aforementioned metabolites was significantly ameliorated in the high-dose quercetin (50 mg/(kg bw day)) plus mixture-OPs-treated group compared with the mixture-OPs-treated group ( p < 0.05). However, the intensities of these metabolites in the high-dose quercetin plus mixture-OPs-treated group were still significantly different from those of the control group ( p < 0.05). Results indicated that high dose of quercetin elicits a partial protective effect on the toxicity induced by mixture OPs, including fatty acid and energy metabolism, antioxidant defense system, DNA damage, and liver and kidney function. PMID- 27251766 TI - Evaluation of nanoselenium (Nano-Se) effect on hematological and serum biochemical parameters of rat in experimentally lead poisoning. AB - The present study was designed to evaluate the effect of nanoselenium (Nano-Se) on hematological and biochemical parameters of rats experimentally intoxicated with lead (Pb). Thirty male rats were randomly divided into six groups as follows: the control, selenite, Nano-Se, Pb group, Pb + selenite, and Pb + Nano Se groups. After 35 days, blood was collected from rats and hematology and serum biochemical parameters of oxidative stress were measured. The thiobarbituric acid reactive substances (TBARS) level of Pb group was significantly higher than other groups. Also, TBARS level was significantly lower in the Pb + Nano-Se group than Pb + selenite group. The serum superoxide dismutase activities were significantly lower in Pb group than the control, Pb + selenite, and Pb + Nano-Se groups. The catalase activities in the Pb group showed no significant change when compared to other groups. In the Pb group, packed cell volume was lower than the control group. A significant difference was observed between the control group and the Pb, Pb + selenite, and Pb + Nano-Se groups. In the Pb group, the numbers of white blood cell (WBC) decreased in comparison with the control group. Also, there was significant increase in WBC counts in the Pb + Nano-Se and Pb + selenite groups in comparison with Pb group. The number of lymphocytes in the Pb group decreased in comparison with the control group. By comparing the means of the Pb + Nano-Se and Pb + selenite groups together, it was determined that there were significant differences in the lymphocytes and neutrophil counts. In conclusion, usage of selenium compounds particularly Nano-Se particles inhibits the adverse effects of Pb on antioxidant activity and immune system function in the Pb poisoning. PMID- 27251767 TI - Facile access to a Ge(ii) dication stabilized by isocyanides. AB - Herein, we introduce isocyanide as a ligand in main group chemistry and describe the facile isolation of a Ge(ii) dication. The reaction of 2,6 dimethylphenylisocyanide with GeCl2 leads to the formation of a Ge(ii) dication with two [GeCl3](-) molecules as counter anions. The dicationic Ge(ii) center is bound to four isocyanide ligands and also holds a lone pair of electrons. DFT calculations reveal that the dication is stabilized only by sigma-donation from the four isocyanide ligands. Natural population analysis gives a charge of +0.74 on the Ge(ii) center, indicating that the positive charge is shared by the isocyanide substituents. PMID- 27251768 TI - Wide angle and narrow-band asymmetric absorption in visible and near-infrared regime through lossy Bragg stacks. AB - Absorber is an important component in various optical devices. Here we report a novel type of asymmetric absorber in the visible and near-infrared spectrum which is based on lossy Bragg stacks. The lossy Bragg stacks can achieve near-perfect absorption at one side and high reflection at the other within the narrow bands (several nm) of resonance wavelengths, whereas display almost identical absorption/reflection responses for the rest of the spectrum. Meanwhile, this interesting wavelength-selective asymmetric absorption behavior persists for wide angles, does not depend on polarization, and can be ascribed to the lossy characteristics of the Bragg stacks. Moreover, interesting Fano resonance with easily tailorable peak profiles can be realized using the lossy Bragg stacks. PMID- 27251769 TI - Prostate cancer characteristics and outcome in renal transplant recipients: results from a contemporary single center study. AB - BACKGROUND: Prostate cancer (PCa) incidence is expected to increase in renal transplant recipients (RTR) with no clear nor contemporary data on management and oncological outcome. METHODS: We conducted a retrospective single center study of RTR diagnosed with PCa after transplantation between 2000 and 2013. Demographics, PCa characteristics, and treatment were assessed. For each RTR in radical prostatectomy (RP) subset, we included 4 non-organ transplant patients who underwent RP by the same surgeons, and compared pre-operative and post-operative oncological features, and biochemical recurrence (BCR) rate. RESULTS: Twenty-four RTR were included (PCa incidence 1.5%). Mean follow-up was 47 months. PCa was mostly localized (n=21, 87.5%) with treatments including RP (n=16, 76.2%), brachytherapy (n=3, 14.3%), radiation therapy (n=1, 4.7%), and active surveillance (n=1, 4.7%). No graft loss due to PCa treatment was reported. Nineteen RTR with localized PCa (90.5%) were free from BCR. Considering RP subset, no difference in PCa characteristics at diagnosis and BCR rate was found between RTR (n=16) and control patients (n=64). CONCLUSIONS: Localized PCa following renal transplantation was not associated with adverse features as compared with non-transplant patients. Standard treatments could be proposed to RTR with satisfying results both on oncological outcome and graft function. PMID- 27251770 TI - Validating alternative methodologies to estimate the regime of temporary rivers when flow data are unavailable. AB - Hydrological data for assessing the regime of temporary rivers are often non existent or scarce. The scarcity of flow data makes impossible to characterize the hydrological regime of temporary streams and, in consequence, to select the correct periods and methods to determine their ecological status. This is why the TREHS software is being developed, in the framework of the LIFE Trivers project. It will help managers to implement adequately the European Water Framework Directive in this kind of water body. TREHS, using the methodology described in Gallart et al. (2012), defines six transient 'aquatic states', based on hydrological conditions representing different mesohabitats, for a given reach at a particular moment. Because of its qualitative nature, this approach allows using alternative methodologies to assess the regime of temporary rivers when there are no observed flow data. These methods, based on interviews and high resolution aerial photographs, were tested for estimating the aquatic regime of temporary rivers. All the gauging stations (13) belonging to the Catalan Internal Catchments (NE Spain) with recurrent zero-flow periods were selected to validate this methodology. On the one hand, non-structured interviews were conducted with inhabitants of villages near the gauging stations. On the other hand, the historical series of available orthophotographs were examined. Flow records measured at the gauging stations were used to validate the alternative methods. Flow permanence in the reaches was estimated reasonably by the interviews and adequately by aerial photographs, when compared with the values estimated using daily flows. The degree of seasonality was assessed only roughly by the interviews. The recurrence of disconnected pools was not detected by flow records but was estimated with some divergences by the two methods. The combination of the two alternative methods allows substituting or complementing flow records, to be updated in the future through monitoring by professionals and citizens. PMID- 27251771 TI - Profiles and changes in stimulant use in Belgium in the period of 2011-2015. AB - Adapting illicit drug policy strategies requires detailed knowledge on types and amounts of substances consumed by the target population. In this study, we applied wastewater-based epidemiology to detect spatio-temporal changes in the relative amounts of stimulants (amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), cocaine) used in seven locations in Belgium over 2011-2015. Clear geographical differences were observed with stimulant users in large cities (Antwerp, Brussels) showing a preference for cocaine, while amphetamine use was most abundant in smaller cities (Geraardsbergen, Koksijde, Lier, Ninove, Ostend). Results obtained across odifferent years revealed that the investigated substances had a stable share in the total amount of stimulants used, suggesting that habits of stimulant use remained constant, although differences in absolute amounts were observed across years. Investigation of the weekly pattern in stimulant use showed an increase in the use of MDMA on the weekends compared to cocaine and amphetamine. PMID- 27251772 TI - Flt1/VEGFR1 heterozygosity causes transient embryonic edema. AB - Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1(+/-)) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1(+/-) capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1(+/-) embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1(-/-) mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1(+/-); Aspp1(-/-) mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype. PMID- 27251773 TI - Variations of lumbrical muscle innervation patterns in the hand, focusing on the dual innervation of the third lumbrical muscle. AB - INTRODUCTION: This study was conducted to clarify the innervation patterns of the lumbrical muscles by identifying the origin of the nerve fascicles innervating these muscles. METHODS: The lumbricals in the hand were investigated in 50 specimens of embalmed Korean adult cadavers. RESULTS: Dual innervation of the third lumbrical was most frequently observed in 64.0%. The third lumbrical was innervated by a branch arising from the median nerve (MN) distal to site at which the superficial branch of the ulnar nerve (sUN) joins the MN in 34%. When separating and tracing the nerve fascicles from the MN distal to the communicating branch from the sUN to MN, the fascicles contained parts of the MN and sUN in 18% and part of the MN in 16%. CONCLUSIONS: These results will be helpful for accurate diagnoses, surgical procedures, and electrophysiological examinations in lesions of the MN and ulnar nerve in the hand. Muscle Nerve, 2016 Muscle Nerve 55: 160-165, 2017. PMID- 27251774 TI - MRI of the knees in asymptomatic adolescent soccer players: A case-control study. AB - PURPOSE: To determine the range of asymptomatic abnormal findings in adolescent soccer players at 3.0T MRI of the knee. MATERIALS AND METHODS: In all, 87 knees of asymptomatic 14-17-year-old male adolescents were evaluated at 3T, using a standardized examination protocol comprising four sequences: two fat-suppressed T2 -weighted fast spin-echo sequences (T2 FSE), in the sagittal (repetition time / echo time [TR/TE], 5.300/71, echo train length [ETL] 17) and coronal planes (TR/TE, 4234/70, ETL 17), one fat-suppressed proton density (PD) sequence in the axial plane (TR/TE, 2.467/40, ETL 9), and one T1 -weighted spin-echo (T1 SE) sequence in the sagittal plane (TR/TE, 684/12.5). Soccer players (46 knees) were paired with controls (41 knees) by age and weight. Bone marrow, articular cartilage, meniscus, tendons, ligaments, fat pad abnormalities, and joint fluid were assessed. RESULTS: One or more abnormalities were detected in 31 knees (67.4%) in the soccer player group, compared to 20 knees (48.8%) in the control group. The prevalence of bone marrow edema was higher in the soccer group (19 knees, 41.3%) than in the control group (3 knees, 7.3%), P = 0.001. Other abnormalities found in this sample (joint effusion, cartilage lesions, tendinopathy, ganglion cysts, and infrapatellar fat pat edema) were not significantly different between the two study groups. CONCLUSION: Asymptomatic adolescents had a high prevalence of abnormal findings on knee imaging, especially bone marrow edema. This prevalence was higher among soccer players. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:59-65. PMID- 27251775 TI - Semirational Protein Engineering of CYP153AM.aq. -CPRBM3 for Efficient Terminal Hydroxylation of Short- to Long-Chain Fatty Acids. AB - The regioselective terminal hydroxylation of alkanes and fatty acids is of great interest in a variety of industrial applications, such as in cosmetics, in fine chemicals, and in the fragrance industry. The chemically challenging activation and oxidation of non-activated C-H bonds can be achieved with cytochrome P450 enzymes. CYP153AM.aq. -CPRBM3 is an artificial fusion construct consisting of the heme domain from Marinobacter aquaeolei and the reductase domain of CYP102A1 from Bacillus megaterium. It has the ability to hydroxylate medium- and long-chain fatty acids selectively at their terminal positions. However, the activity of this interesting P450 construct needs to be improved for applications in industrial processes. For this purpose, the design of mutant libraries including two consecutive steps of mutagenesis is demonstrated. Targeted positions and residues chosen for substitution were based on semi-rational protein design after creation of a homology model of the heme domain of CYP153AM.aq. , sequence alignments, and docking studies. Site-directed mutagenesis was the preferred method employed to address positions within the binding pocket, whereas diversity was created with the aid of a degenerate codon for amino acids located at the substrate entrance channel. Combining the successful variants led to the identification of a double variant-G307A/S233G-that showed alterations of one position within the binding pocket and one position located in the substrate access channel. This double variant showed twofold increased activity relative to the wild type for the terminal hydroxylation of medium-chain-length fatty acids. This variant furthermore showed improved activity towards short- and long-chain fatty acids and enhanced stability in the presence of higher concentrations of fatty acids. PMID- 27251776 TI - Bilateral cochlear implantation under local anaesthesia in a young adult - A case report. AB - OBJECTIVE: Cochlear implantation is routinely performed under general anaesthesia in most centres in the world. There have been reports of this surgery being performed under local anaesthesia and sedation for unilateral cochlear implantation. Our case study reports the first bilateral cochlear implantation carried out under local anaesthesia with sedation. This paper outlines the protocol used and discusses the challenges and advantages of the procedure being performed under local anaesthesia. CASE STUDY: A 28-year-old female with a history of multidrug-resistant tuberculosis presented with bilateral severe to profound sensorineural hearing loss. On evaluation, she was found to be a suitable candidate for cochlear implantation. However, she was clinically unfit to undergo the surgery under general anaesthesia. After counselling the patient, the decision to undertake the procedure under local anaesthesia was made. The procedure took 105 min and was uneventful. The patient was discharged the next day Conclusion: In the hands of an experienced surgeon and anaesthesiology team, bilateral cochlear implantation is possible under local anaesthesia. Patient motivation and cooperation are extremely important for the procedure to be done under local anaesthesia. This is an option for patients needing cochlear implantation who are medically unfit for general anaesthesia. PMID- 27251778 TI - Smarty plants. PMID- 27251779 TI - Transposable elements: Microbiomes in the genomes. PMID- 27251777 TI - Distinct genetic profiles of extracranial and intracranial acral melanoma metastases. AB - BACKGROUND: There is limited knowledge of the genetic alterations in acral melanoma metastases at different anatomic sites. Here, we characterized the genetic abnormalities of metastases in a 51-year-old man with stage IIIC heel melanoma who developed concomitant brain and cutaneous metastases in spite of multiple treatment modalities. METHODS: Melanoma cells were isolated following palliative resection of the patient's cortical tumor and biopsy of cutaneous thigh metastasis. Mutational analysis using polymerase chain reaction amplification and BLAST, as well as exome sequencing (160 Mb coverage) was performed on the tumors, cell lines generated thereof and normal lymph nodes. RESULTS: All specimens had neuroblastoma RAS viral oncogene homolog Q61K mutations. There was a 40-fold higher somatic mutation frequency in the brain metastasis compared to the cutaneous metastasis. The former showed truncations of DNA mismatch repair genes (MLH1 and MSH2), and non-canonical BRAF (v-raf murine sarcoma viral oncogene homolog B1), PIK3CA and NF-1 mutations not observed in the extracranial lesion. Genomic profiling of each cell line was concordant with the respective original tumor tissue. CONCLUSIONS: We present the mutational differences between brain and cutaneous acral melanoma metastases in a patient with concomitant lesions. Further genetic and functional studies are needed to understand the biology of metastatic disease appearing at different sites. PMID- 27251780 TI - Systems pharmacology to predict drug safety in drug development. AB - Ensuring that drugs are safe and effective is a very high priority for drug development and the US Food and Drug Administration review process. This is especially true today because of faster approval times and smaller clinical trials, especially in oncology and rare diseases. In light of these trends, systems pharmacology is seen as an essential strategy to understand and predict adverse drug events during drug development by analyzing interactions between drugs and multiple targets rather than the traditional "one-drug-one-target" approach. This commentary offers an overview of the current trends and challenges of using systems pharmacology to reduce the risks of unintended adverse events. PMID- 27251781 TI - Clustering siRNA conjugates for MMP-responsive therapeutics in chronic wounds of diabetic animals. AB - The MMP-responsive breakdown of siRNA clusters was translated to site-specific gene transfection and enhanced wound healing in diabetic ulcers. MMP-2 siRNA was chemically tethered to the end of multi-armed PEG via MMP-cleavable linkers (4PEG siRNA) and subsequently clustered into submicron particles complexed with LPEI. 4PEG-siRNA was more tightly complexed with LPEI and the associated cluster showed higher resistance against RNase attack, in comparison to naked siRNA. Because the size of the clusters increased depending on the increase in charge ratio of LPEI to siRNA, cellular uptake of the 4PEG-siRNA/LPEI cluster was significantly attenuated due to the huge size of the cluster. However, upon MMP treatment, the cluster dissociated into smaller particles and was efficiently endocytosed by cells. An in vivo fluorescence resonance energy transfer (FRET) study also revealed that the clusters were effectively dissociated in MMP-rich environments of dorsal wounds in diabetic animals. In addition, diabetic ulcers treated with the clusters showed a faster wound closure rate and the recovered tissue expressed a larger amount of cytokeratin along with a lower expression level of MMP-2 compared to the other groups. PMID- 27251782 TI - Lithium poisoning in the intensive care unit: predictive factors of severity and indications for extracorporeal toxin removal to improve outcome. AB - CONTEXT: Lithium is responsible for life-threatening poisoning, not consistently improved by extracorporeal toxin removal (ECTR). OBJECTIVE: Our aim was to identify predictive factors on admission of poisoning severity and based on an evaluation of practice, report indications for ECTR susceptible to improve outcome Methods: We performed a retrospective cohort study including all lithium poisoned patients admitted to the ICU in a university hospital. The usual clinical, biological and toxicological variables were collected. Poisoning severity was defined by seizures, catecholamine infusion, mechanical ventilation >48 h and/or fatality. Univariate followed by multiple logistic regression analyses were performed to identify prognosticators of poisoning severity and ECTR use. RESULTS: From 1992 to 2013, 128 lithium-poisoned patients including acutely (10%), acute-on-chronically (63%) and chronically poisoned patients (27%) were included. The presumed ingested dose of lithium was 17.0 g [8.0-24.5] (median [25th-75th percentiles]). Serum lithium concentrations were 2.6 mmol/l [1.5-4.6], 2.8 mmol/l [1.8-4.5] and 2.8 mmol/l [2.1-3.0] on admission, peaking at 3.6 mmol/l [2.6; 6.2], 4.3 mmol/l [2.4; 6.2] and 2.8 mmol/l [2.1; 3.1] in the three groups, respectively. Severe poisoning occurred in 48 patients (38%) including four fatalities. Using the regression analysis, predictive factors of poisoning severity were Glasgow coma score <=10 (Odds ratio (OR), 11.1; 95% confidence interval (CI), [4.1-33.3], p < 0.0001) and lithium concentration >=5.2 mmol/l (OR, 6.0; CI, [1.7-25.5], p = 0.005). Ninety-eight patients (77%) developed acute kidney injury according to KDIGO criteria and 22 (17%) were treated with ECTR. Peak lithium concentration >=5.2 mmol/l (OR, 22.4; CI, [6.4 96.4]; p < 0.0001) and peak creatinine concentration >=200 MUmol/l (OR, 5.0; CI, [1.4-19.2]; p = 0.01) were associated with ECTR use. Only 21/46 patients who presented one of these two criteria were actually treated with ECTR. More significant neurological impairment persisted on discharge in patients not treated with ECTR (p = 0.0007) despite not significantly shorter length of ICU stay. CONCLUSIONS: Lithium poisoning is responsible for severe impairments but rare fatalities. Severity can be predicted on admission using Glasgow coma score and lithium concentration. Our results suggest that ECTR could be indicated if serum lithium >=5.2 mmol/l or creatinine >=200 MUmol/l. PMID- 27251783 TI - Hormetic Effect of Chronic Hypergravity in a Mouse Model of Allergic Asthma and Rhinitis. AB - We aimed to evaluate the effect of chronic hypergravity in a mouse model of allergic asthma and rhinitis. Forty BALB/c mice were divided as: group A (n = 10, control) sensitized and challenged with saline, group B (n = 10, asthma) challenged by intraperitoneal and intranasal ovalbumin (OVA) to induce allergic asthma and rhinitis, and groups C (n = 10, asthma/rotatory control) and D (n = 10, asthma/hypergravity) exposed to 4 weeks of rotation with normogravity (1G) or hypergravity (5G) during induction of asthma/rhinitis. Group D showed significantly decreased eosinophils, neutrophils, and lymphocytes in their BAL fluid compared with groups B and C (p < 0.05). In real-time polymerase chain reaction using lung homogenate, the expression of IL-1beta was significantly upregulated (p < 0.001) and IL-4 and IL-10 significantly downregulated (p < 0.05) in group D. Infiltration of inflammatory cells into lung parenchyma and turbinate, and the thickness of respiratory epithelium was significantly reduced in group D (p < 0.05). The expression of Bcl-2 and heme oxygenase-1 were significantly downregulated, Bax and extracellular dismutase significantly upregulated in Group D. Therefore, chronic hypergravity could have a hormetic effect for allergic asthma and rhinitis via regulation of genes involved in antioxidative and proapoptotic pathways. It is possible that we could use hypergravity machinery for treating allergic respiratory disorders. PMID- 27251784 TI - A qualitative study of patient experiences of Type 2 Diabetes care delivered comparatively by General Practice Nurses and Medical Practitioners. AB - AIMS AND OBJECTIVES: To explore patient experiences of type 2 diabetes mellitus care delivered by general practice nurses in collaboration with the general practitioner. BACKGROUND: Australian general practice nurses are expanding their role in multidisciplinary type 2 diabetes care with limited research on patient perceptions of care provision within this collaborative model. DESIGN: Qualitative interpretive. METHODS: Purposeful sampling was used to invite the patients (n = 10). Data were collected from semi-structured face-to-face interviews. Braun and Clarke's () inductive coding thematic analysis process was used to interpret the data. RESULTS: All participants experienced their General Practice Nurse consultation as a clinical assessment for their General Practitioner. While they appreciated the extra time with the General Practice Nurse, they were unsure of the purpose of the consultation beyond clinical assessment. They described the ongoing challenge of living with T2DM and identified a need for additional information and advice. CONCLUSION: The results suggest that the model of general practice nurse type 2 diabetes care has an important role to play in the delivery of effective ongoing care of patients. However, this role requires further development to ensure that it is understood by the patients as a role that not only conducts clinical assessments but also provides relevant education and self-management support as part of a collaborative approach to care delivery with General Practitioners. RELEVANCE TO PRACTICE: The findings are relevant to primary health care clinicians providing diabetes care to inform more relevant supportive care by general practice nurses. PMID- 27251785 TI - Involving users and carers in the assessment of preregistration nursing students' clinical nursing practice: a strategy for patient empowerment and quality improvement? AB - AIMS AND OBJECTIVES: To examine (1) nursing lecturers' and (2) preregistration nursing students' perspectives of user and carer involvement in the formal assessment of preregistration nursing students' clinical practice. BACKGROUND: The involvement of service users and carers in the assessment of clinical practice in nursing education is a recent phenomenon. The Nursing and Midwifery Council Standards in the UK clearly reflect a shift in thinking from paternalistic approaches to person-centred approaches. This shift in thinking includes service user and carer involvement in student nursing assessment and there is evidence that this is being developed in several countries. DESIGN: Located in the interpretive paradigm, data from a two-staged, multicentre qualitative study are presented. METHODS: Interpretive analysis of semi structured, one to one interviews with nursing lecturers (n = 15) and focus groups with nursing students (n = 51) across 11 Higher Educational Institutions. RESULTS: There is a strong commitment for working alongside service users and carers in the education and training of nursing students; however, involving service users and carers in formal practice assessment is identified as more challenging compared with other areas of service user/carer involvement. Service user/carers should provide feedback/review or comment, but not necessarily formal, summative 'assessment'. CONCLUSIONS: The evidence base for involving users and carers in assessment is limited. Involvement of users and carers in providing feedback to nursing students is welcomed. However, concerns exist about the preparedness of users and carers for formal clinical assessment. RELEVANCE TO CLINICAL PRACTICE: Discussion and clarification with clinical mentors and user and carer groups is necessary to understand if they agree with the policy direction of user and carer involvement in the assessment of nursing students. Quality assurance concerns are raised by students and lecturers when involving user and carer in assessing nursing students' clinical skills. Mentors are seen as key to this process, but little is known about their perspectives. PMID- 27251786 TI - Sharing Progress in Neonatal (SPIN) Lung and Brain. PMID- 27251787 TI - The effects of intravenous lidocaine before propofol induction in premedicated dogs. AB - OBJECTIVE: The effects of lidocaine, administered before induction of anaesthesia with propofol, on arterial blood pressure, heart rate, respiratory rate, cough reflex, ease of intubation, extrapyramidal signs and required dose of propofol in healthy premedicated dogs were evaluated. METHODS: Twenty-four client-owned dogs were premedicated intramuscularly with 1 ug/kg dexmedetomidine and 0.2 mg/kg methadone, and randomly allocated to receive 2 mg/kg lidocaine (group L) or saline (group P) 120 seconds before induction of anaesthesia with propofol. Heart rate, non-invasive arterial blood pressure and respiratory rate were assessed at pre-established intervals. Quality of intubation, cough reflex and the occurrence of adverse effects were scored according to predefined scales. The total amount of propofol administered was also recorded. RESULTS: Cardiovascular and respiratory variables changed over time but were not significantly different between treatments. No significant differences between groups were found for the incidence of coughing, quality of intubation, adverse effects and propofol intubation dose. CLINICAL SIGNIFICANCE: Intravenous administration of lidocaine 2 mg/kg before propofol induction was not associated with significant cardiovascular and respiratory benefits compared to standard induction and did not result in a propofol dose-sparing effect or improvement of the quality of intubation in dogs premedicated with dexmedetomidine and methadone. PMID- 27251788 TI - Efficacy of CT-guided localization followed by video-assisted thoracoscopic surgery in children with tiny pulmonary nodules. AB - CT-guided localization followed by video-assisted thoracoscopic surgery was performed in three children with pulmonary nodules less than 5 mm in diameter. The patients' respective primary diagnoses were Wilms tumor, hepatoblastoma, and osteosarcoma of the femur. The pulmonary nodules were marked preoperatively by a percutaneously placed hook-wire or dye under CT guidance. Although none of the nodules was grossly detected during the operation, they were correctly resected under the guidance of the hook-wire wound or dye. A histological assessment revealed viable metastatic lesions in the case of hepatoblastoma, completely necrotic lesions in the case of Wilms tumor, and inflammatory nodules in the case of osteosarcoma. CT-guided localization followed by video-assisted thoracoscopic surgery appears to be a beneficial procedure in children with tiny pulmonary nodules. PMID- 27251789 TI - Phosphoproteomic Analyses of NRAS(G12) and NRAS(Q61) Mutant Melanocytes Reveal Increased CK2alpha Kinase Levels in NRAS(Q61) Mutant Cells. AB - In melanoma, mutant and thereby constantly active neuroblastoma rat sarcoma (NRAS) affects 15-20% of tumors, contributing to tumor initiation, growth, invasion, and metastasis. Recent therapeutic approaches aim to mimic RAS extinction by interfering with critical signaling pathways downstream of the mutant protein. This study investigates the phosphoproteome of primary human melanocytes bearing mutations in the two hot spots of NRAS, NRAS(G12) and NRAS(Q61). Stable isotope labeling by amino acids in cell culture followed by mass spectrometry identified 14,155 spectra of 3,371 unique phosphopeptides mapping to 1,159 proteins (false discovery rate < 2%). Data revealed pronounced PI3K/AKT signaling in NRAS(G12V) mutant cells and pronounced mitogen-activated protein kinase (MAPK) signaling in NRAS(Q61L) variants. Computer-based prediction models for kinases involved, revealed that CK2alpha is significantly overrepresented in primary human melanocytes bearing NRAS(Q61L) mutations. Similar differences were found in human NRAS(Q61) mutant melanoma cell lines that were also more sensitive to pharmacologic CK2alpha inhibition compared with NRAS(G12) mutant cells. Furthermore, CK2alpha levels were pronounced in patient samples of NRAS(Q61) mutant melanoma at the mRNA and protein level. The preclinical findings of this study reveal that codon 12 and 61 mutant NRAS cells have distinct signaling characteristics that could allow for the development of more effective, mutation-specific treatment modalities. PMID- 27251791 TI - Oral Metformin Ameliorates Bleomycin-Induced Skin Fibrosis. PMID- 27251790 TI - Association of Melanocortin-1 Receptor Variants with Pigmentary Traits in Humans: A Pooled Analysis from the M-Skip Project. PMID- 27251792 TI - Sex Differences in Age at Primary Melanoma Diagnosis in a Population-Based Analysis (US Surveillance, Epidemiology, and End Results, 2005-2011). PMID- 27251793 TI - Fragmented QRS Can Optimize the Exercise Stress Test Results. PMID- 27251794 TI - Do maize models capture the impacts of heat and drought stresses on yield? Using algorithm ensembles to identify successful approaches. AB - Stresses from heat and drought are expected to increasingly suppress crop yields, but the degree to which current models can represent these effects is uncertain. Here we evaluate the algorithms that determine impacts of heat and drought stress on maize in 16 major maize models by incorporating these algorithms into a standard model, the Agricultural Production Systems sIMulator (APSIM), and running an ensemble of simulations. Although both daily mean temperature and daylight temperature are common choice of forcing heat stress algorithms, current parameterizations in most models favor the use of daylight temperature even though the algorithm was designed for daily mean temperature. Different drought algorithms (i.e., a function of soil water content, of soil water supply to demand ratio, and of actual to potential transpiration ratio) simulated considerably different patterns of water shortage over the growing season, but nonetheless predicted similar decreases in annual yield. Using the selected combination of algorithms, our simulations show that maize yield reduction was more sensitive to drought stress than to heat stress for the US Midwest since the 1980s, and this pattern will continue under future scenarios; the influence of excessive heat will become increasingly prominent by the late 21st century. Our review of algorithms in 16 crop models suggests that the impacts of heat and drought stress on plant yield can be best described by crop models that: (i) incorporate event-based descriptions of heat and drought stress, (ii) consider the effects of nighttime warming, and (iii) coordinate the interactions among multiple stresses. Our study identifies the proficiency with which different model formulations capture the impacts of heat and drought stress on maize biomass and yield production. The framework presented here can be applied to other modeled processes and used to improve yield predictions of other crops with a wide variety of crop models. PMID- 27251799 TI - A novel reconstruction method for giant incisional hernia: Hybrid laparoscopic technic. AB - BACKGROUND AND OBJECTIVES: Laparoscopic reconstruction of ventral hernia is a popular technic today. Patients with large defects have various difficulties of laparoscopic approach. In this study, we aimed to present a new reconstruction technic that combines laparoscopic and open approach in giant incisional hernias. MATERIALS AND METHODS: Between January 2006 and August 2012, 28 patients who were operated consequently for incisional hernia with defect size over 10 cm were included in this study and separated into two groups. Group 1 (n = 12) identifies patients operated with standard laparoscopic approach, whereas Group 2 (n = 16) labels laparoscopic technic combined with open approach. Patients were evaluated in terms of age, gender, body mass index (BMI), mean operation time, length of hospital stay, surgical site infection (SSI) and recurrence rate. RESULTS: There were 12 patients in Group 1 and 16 patients in Group 2. Mean length of hospital stay and SSI rates are similar in both groups. Postoperative seroma formation was observed in 6 patients for Group 1 and in only 1 patient for Group 2. Group 1 had 1 patient who suffered from recurrence where as Group 2 had no recurrence. DISCUSSION: Laparoscopic technic combined with open approach may safely be used as an alternative method for reconstruction of giant incisional hernias. PMID- 27251795 TI - Capnocytophaga canimorsus bacteremia: clinical features and outcomes from a Helsinki ICU cohort. AB - BACKGROUND: Capnocytophaga canimorsus is a gram-negative rod capable of causing severe sepsis or septic shock. We studied the characteristics of patients with C. canimorsus bacteremia treated in intensive care unit (ICU). METHODS: Patients with C. canimorsus bacteremia in the Helsinki University Hospital district from 2005 to 2014 were retrospectively reviewed using laboratory database and electronical patient records. RESULTS: We identified 65 patients with C.canimorsus bacteremia. Of these, 16 (25%) were treated in an ICU. The most commonly affected organ systems were coagulation (94%) and kidney (69%). Mortality of ICU treated patients was 19%. Three survivors underwent lower limb amputations for gangrene. Only 25% of the patients were immune-compromised, but alcohol abuse was common (69%). All patients had a contact with dogs, but only 37% had a history of a dog-bite. CONCLUSION: Capnocytophaga canimorsus infection may present with severe sepsis or septic shock with organ dysfunction, most frequently coagulopathy and acute kidney injury. Previously recognized risk factors are not always present. A dog in a household may be a sufficient exposure for developing a severe form of the disease. The possibility of C. canimorsus infection should be considered in patients with any contact with dogs, even in immunocompetent patients. PMID- 27251803 TI - Laparoscopic retrieval of impacted Dormia basket. AB - For choledocholithiasis, endoscopic management is the first line of treatment. Both Dormia basket and balloon catheter are used to retrieve common bile duct (CBD) stones. Here we present a case of impaction of the Dormia basket during an endoscopic procedure. The patient was managed through laparoscopic choledochotomy, and the basket was found to be impacted with a common bile stone of size 18 mm. The stone was disengaged from the basket and, by holding the tip of the basket, was removed through one of the laparoscopic ports. PMID- 27251804 TI - Laparoscopic resection of a large paraganglioma arising in the organ of Zuckerkandl: Report of a case and review of the literature. AB - Paragangliomas are catecholamine-secreting neuroendocrine tumours arising from chromaffin tissue at extra-adrenal sites. The commonest site for a paraganglioma is the organ of Zuckerkandl. Traditional treatment of paraganglioma of organ of Zuckerkandl (POZ) involves open surgical resection, and only a few cases of laparoscopic approach to this pathology have been reported. We report the successful laparoscopic resection of a large POZ in a 22-year-old woman and review the previous cases reporting a laparoscopic approach to this rare tumour. PMID- 27251809 TI - Laparoscopic splenic artery ligation for hypersplenism in cirrhosis: A case series. AB - BACKGROUND: Splenectomy for the treatment of hypersplenism in patients with cirrhosis (HIC) is related with complications. Laparoscopic splenic artery ligation (LSAL) may be an alternative treatment option. AIMS: To evaluate safety and feasibility of LSAL in the treatment of HIC. PATIENTS AND METHODS: Retrospective analysis of prospectively collected data of ten patients with HIC who were treated with LSAL from October 2012 to February 2015. RESULTS: The median (range) age was 33.2 (13-56) years and sex distribution was equal. The median (range) leukocyte counts (*10(9)/L) before, and at 3, 6 and 12 months after LSAL were 2.2 (0.8-8.2) and 5.65 (2.78-10.7), 4.7 (2.8-7.8) and 4.95 (3.4 7.7) respectively. The median (range) platelet counts (*10(9)/L) before and at 3, 6 and 12 months after LSAL were 25.5 (11-65) and 75 (39-289), 74 (32-184) and 76 (56-251) respectively. Following LSAL, there was a significant improvement in total leucocyte count, platelet count and Model for End-Stage Liver Disease (MELD) score (P < 0.05). Two patients (20%) developed intraoperative bleeding and required conversion; one of these two patients developed splenic cyst that required radiological intervention. Four patients (40%) had post ligation syndrome (PLS) that was managed conservatively. During a median (range) follow-up of 19.5 (5-29) months, one patient (10%) required splenectomy due to inadequate response. CONCLUSION: LSAL is a safe and feasible treatment option for the palliation of symptomatic HIC, however, further prospective trials are necessary for confirmation. PMID- 27251808 TI - Management of gastric leaks after laparoscopic sleeve gastrectomy for morbid obesity: A tertiary care experience and design of a management algorithm. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed 'standalone' bariatric procedure in India. Staple line gastric leaks occur infrequently but cause significant and prolonged morbidity. The aim of this retrospective study was to analyse the management of patients with a gastric leak after LSG for morbid obesity at our institution. PATIENTS AND METHODS: From February 2008 to 2014, 650 patients with different degrees of morbid obesity underwent LSG. Among these, all those diagnosed with a gastric leak were included in the study. Patients referred to our institution with gastric leak after LSG were also included. The time of presentation, site of leak, investigations performed, treatment given and time of closure of all leaks were analysed. RESULTS: Among the 650 patients who underwent LSG, 3 (0.46%) developed a gastric leak. Two patients were referred after LSG was performed at another institution. The mean age was 45.60 +/- 15.43 years. Mean body mass index (BMI) was 44.79 +/- 5.35. Gastric leak was diagnosed 24 h to 7 months after surgery. One was early, two were intermediate and two were late leaks. Two were type I and three were type II gastric leaks. Endoscopic oesophageal stenting was used variably before or after re-surgery. Re-surgery was performed in all and included stapled fistula excision (re-sleeve), suture repair only or with conversion to roux-en-Y gastric bypass or fistula jujenostomy. There was no mortality. CONCLUSION: Leakage closure time may be shorter with intervention than expectant management. Sequence and choice of endoscopic oesophageal stenting and/or surgical re-intervention should be individualized according to clinical presentation. PMID- 27251811 TI - Is rhabdomyolysis an anaesthetic complication in patients undergoing robot assisted radical prostatectomy? AB - BACKGROUND: In patients undergoing robot-assisted radical prostatectomy (RARP), pneumoperitoneum, intraoperative fluid restriction and prolonged Trendelenburg position may cause rhabdomyolysis (RM) due to hypoperfusion in gluteal muscles and lower extremities. In this study, it was aimed to assess effects of body mass index (BMI), comorbidities, intra-operative positioning, fluid restriction and length of surgery on the development of RM in RARP patients during the perioperative period. SUBJECTS AND METHODS: The study included 52 American Society of Anesthesiologists I-II patients aged 50-80 years with BMI >25 kg/m2, who underwent RARP. Fluid therapy with normal saline (1 ml/kg/h) and 6% hydroxyethyl starch 200/05 (1 ml/kg/h) was given during the surgery. Charlson comorbidity index (CCI), operation time (OT) and Trendelenburg time (TT) were recorded. Blood samples for creatine phosphokinase (CPK), blood urea nitrogen, creatinine (Cr), aspartate aminotransferase (AST), alanine transferase (ALT), lactate dehydrogenase (LDH), creatinine kinase-MB, cardiac troponin I and arterial blood gases were drawn at baseline and on 6, 12, 24 and 48 h. RM was defined by serum CPK level exceeding 5000 IU/L. RESULTS: Seven patients met predefined criteria for RM. There were positive correlations among serum CPK and Cr, AST, ALT and LDH levels. However, there was no significant difference in BMI, OT and TT between patients with or without RM (P > 0.05). CCI scores were higher in patients with RM than those without (3.00 +/- 0.58 vs. 2.07 +/- 0.62; P< 0.01). No renal impairment was detected among patients with RM at the post operative period. CONCLUSIONS: It was found that comorbid conditions are more important in the development of RM during RARP rather than BMI, OT or TT. Patients with higher comorbidity are at risk for RM development and that this should be kept in mind at follow-up and when informing patients. PMID- 27251814 TI - A comparative study of two-port versus three-port laparoscopic cholecystectomy. AB - BACKGROUND: Conventionally, laparoscopic cholecystectomy (LC) is performed by using three or four ports of various sizes. As cosmesis is an important aspect of LC, the trend is now towards use of fewer ports, thereby resulting in better cosmesis for patients. The aim of this study was to compare three-port against two-port LC techniques and to see whether there is any advantage in using one technique over the other. SETTINGS AND DESIGN: The study was conducted in the Department of General Surgery of North Eastern Indira Gandhi Regional Institute of Health and Medical Sciences (NEIGRIHMS) hospital in Northeast India. A prospective comparative type of study was designed. An odd number of patients were operated on by using the three-port technique (Group A), whereas an even number of patients were operated on by the two-port technique (Group B). MATERIALS AND METHODS: Sixty patients with symptomatic gallstone disease were included in the study after obtaining informed consent from each of the patients. All patients were operated on under general anaesthesia. STATISTICAL ANALYSIS USED: Statistical analysis was done using SPSS software version 22. RESULTS: There were 51 female patients and 9 male patients. The mean patient age was 38.67 years. There was less operative time in group A but less postoperative pain in group B. Cosmetic appearance and patient satisfaction for the scar were better in group B. CONCLUSIONS: The two-port method appeared to have better acceptability among patients due to lower pain score and better cosmesis. PMID- 27251818 TI - Laparoscopic modified subtotal cholecystectomy for difficult gall bladders: A single-centre experience. AB - AIM: Laparoscopic cholecystectomy (LC) is considered the 'gold standard' intervention for gall bladder (GB) diseases. However, to avoid serious biliovascular injury, conversion is advocated for distorted anatomy at the Calot's triangle. The aim is to find out whether our technique of laparoscopic modified subtotal cholecystectomy (LMSC) is suitable, with an acceptable morbidity and outcome. PATIENTS AND METHODS: A retrospective analysis of prospectively collected data of 993 consecutive patients who underwent cholecystectomy was done at a large District General Hospital (DGH) between August 2007 and January 2015. The data are as follows: Patient's demographics, operative details including intra- and postoperative complications, postoperative stay including follow-up that was recorded and analysed. RESULTS: A total of 993 patients (263 males and 730 female) were included. The median age was 52*(18-89) years. Out of the 993 patients, 979 (98.5%) and 14 (1.5%) were listed for laparoscopic and open cholecystectomy, respectively. Of the 979 patients, 902 (92%) and 64 (6.5%) patients underwent LC +/- on-table cholangiography (OTC) and LMSC +/- OTC, respectively, with a median stay of 1* (0-15) days. Of the 64 patients, 55 (86%) had dense adhesions, 22 (34%) had acute inflammation, 19 (30%) had severe contraction, 12 (19%) had empyema, 7 (11%) had Mirizzi's syndrome and 2 (3%) had gangrenous GB. The mean operative time was 120 * (50-180) min [Table 1]. Six (12%) patients required endoscopic retrograde cholangiopancreatography (ERCP) postoperatively, and there were four (6%) readmissions in a follow-up of 30 * (8-76) months. The remaining 13 (1.3%) patients underwent laparoscopic cholecystectomy converted to an open cholecystectomy. The median stay for open/laparoscopic cholecystectomy converted to open cholecystectomy was 5 * (1 12) days. CONCLUSION: Our technique of LMSC avoided conversion in 6.5% patients and believe that it is feasible and safe for difficult GBs with a positive outcome. PMID- 27251816 TI - Short-stay daycare laparoscopic cholecystectomy at a dedicated daycare centre: Feasible or futile. AB - BACKGROUND: In the last decade, laparoscopic cholecystectomy (LC) has become a regular daycare surgery at many centres across the world. However, only a few centres in India have a dedicated daycare surgery centre, and very few of them have reported their experience. Concerns remain regarding the feasibility, safety and acceptability of the introduction of daycare laparoscopic cholecystectomy (DCLC) in India. There is a need to assess the safety and acceptability of the implementation of short-stay DCLC service at a centre completely dedicated to daycare surgery. PATIENTS AND METHODS: Comprehensive care and operative data were retrospectively collected from a daycare centre of our hospital. Postoperative recovery was monitored by telephone questionnaire on days 0, 1 and 5 postoperatively, including adverse outcomes. RESULTS: A total of 211 patients were admitted for DCLC during the period from November 2011 till November 2014, of whom 211 were discharged on the day of surgery. Two hundred and two patients could be discharged within 6 h of surgery. Mean operation time was 72 min. No patient required admission. No patient needed conversion to open surgery. Only 1 patient was re-admitted due to bilioma formation and was managed with minimal intervention. CONCLUSION: The introduction of short-stay DCLC in India is feasible and acceptable to patients. High body mass index (BMI) in otherwise healthy patients and selective additional procedures are not contraindications for DCLC. PMID- 27251819 TI - Inflammatory stricture of the right ureter following perforated appendicitis: The first Indian report. AB - Perforated appendicitis leading to inflammatory stricture of the right ureter is a rarity. We present this fairly uncommon case of a patient who developed a stricture of the right ureter secondary to an ongoing inflammatory process in the peritoneum and retroperitoneum. A perforated appendicitis was operated upon, and on follow-up the mild hydronephrosis had worsened. Stenting of the right ureter completely solved the problem. PMID- 27251820 TI - Reversal of the Hartmann's procedure: A comparative study of laparoscopic versus open surgery. AB - BACKGROUND: The Hartmann's operation, although less frequently performed today, is still used when initial colonic anastomosis is too risky in the short term. However, the subsequent procedure to restore gastrointestinal continuity is associated with significant morbidity and mortality. PATIENTS AND METHODS: The review of an institutional review board (IRB)-approved prospectively maintained database provided data on the Hartmann's reversal procedure performed by either laparoscopic or open technique at our institution. The data collected included: demographic data, operative approach, conversion for laparoscopic cases and perioperative morbidity and mortality. RESULTS: Over a 14-year period from January 1997 to August 2011, 74 Hartmann's reversal procedures were performed (laparoscopic surgery-49, open surgery-25). The average age was 55 years for the laparoscopic and 57 years for the open surgery group, respectively. Male patients represent 61% of both groups. There was no significant difference in operative time between the two groups (149 min vs 151 min; P = 0.95), and there was a tendency to lower morbidity (3/49-7.3% vs 4/25-16%; P = 0.24) in the laparoscopic surgery group. In the laparoscopic group, eight patients (16.3%) were converted to open surgery, mostly due to severe adhesions. The length of hospital stay was significantly shorter for the laparoscopic group (5 days vs 7 days; P = 0.44). CONCLUSIONS: The Hartmann's reversal procedure can be safely performed in the majority of the cases using a laparoscopic approach with a low morbidity rate and achieving a shorter hospital stay. PMID- 27251821 TI - Hepatic artery reconstruction following iatrogenic injury during laparoscopic distal pancreatectomy: Minimal access surgery is new horizon. AB - Although minimally invasive surgery has evolved in every field of surgery, its use in vascular surgery is limited to major vessel diseases only. A 23-year-old female presented with a cystic lesion in the distal body and the tail of the pancreas. Triphasic computed tomography (CT) abdomen revealed a 4.5 cm * 3.2 cm sized mass with calcifications. A diagnosis of the mucinous cystic neoplasm in the distal body and the tail of the pancreas was made and the patient was planned for laparoscopic distal pancreatectomy. During the procedure, hepatic artery was accidentally injured due to its anomalous course. The artery was then reconstructed laparoscopically using left gastric artery as conduit. The time duration of the procedure was 45 min and blood loss was approximately 75 mL. The patient recovered well and the postoperative Doppler study revealed normal blood flow. Medium-vessel surgery through laparoscopic approach is feasible and safe in select cases, while availing benefits of laparoscopy. PMID- 27251822 TI - Clinical anatomy of the inferior epigastric artery with special relevance to invasive procedures of the anterior abdominal wall. AB - INTRODUCTION: Injury to the inferior epigastric artery (IEA) has been reported following lower abdominal wall surgical incisions, abdominal peritoneocentesis and trocar placements at laparoscopic port sites, resulting in the formation of abdominal wall haematomas that may expand considerably due to lack of tissue resistance. The aim of this study was to localise its course in relation to standard anatomic landmarks and suggest safe areas for performance of invasive procedures. MATERIALS AND METHODS: Sixty IEAs of 30 adult cadavers (male = 19; female = 11) were dissected and the course of the IEA noted in relation to the mid-inguinal point, anterior superior iliac spine (ASIS) and umbilicus. RESULTS: The mean distance of the IEA from the midline was 4.45 +/- 1.42 cm at the level of the mid-inguinal point, 4.10 +/- 1.15 cm at the level of ASIS and 4.49 +/- 1.15 cm at the level of umbilicus. There was an average of 3.3 branches per IEA with more branches arising from its lateral aspect. The IEA was situated within one-third (32%) of the distance between the midline and the sagittal plane through ASIS at all levels. CONCLUSION: To avoid injury to IEA, trocars can be safely inserted 5.5 cm [mean + 1 standard deviation (SD)] away from the midline (or) slightly more than one-third of the distance between the midline and a sagittal plane running through ASIS. These findings may be useful not only for laparoscopic procedures but also for image-guided biopsy, abdominal paracentesis, and placement of abdominal drains. PMID- 27251823 TI - Modified uniportal video-assisted thoracic surgery in children. AB - Video-assisted thoracic surgery (VATS) has been traditionally performed by a multi-port approach, but uniportal VATS is gaining popularity among thoracic surgeons. The use of only one intercostal space may result in less pain, but competition among camera and operating instruments may be a disadvantage. In children, the limited space in the thorax makes the uniportal VATS difficult to accomplish. We present a modification of the uniportal VATS, using a single skin incision but placing the thoracoscope in the superior or inferior intercostal space relative to the working instruments to increase instrument range of motion within a single intercostal space. PMID- 27251825 TI - Life-threatening upper gastrointestinal bleeding due to gastric Dieulafoy's lesion: Successful minimally-invasive management. AB - Dieulafoy's lesion (DL) is a relatively rare, but potentially life-threatening condition. It accounts for 1-2% of acute gastrointestinal bleedings. Its serious nature makes it necessary for early diagnosis and treatment. This is a case report of a patient who presented with life-threatening haematemesis due to gastric Dieulafoy's that was successfully treated laparoscopically after failed endotherapy. PMID- 27251826 TI - Current status of mini-gastric bypass. AB - Mini-gastric bypass (MGP) is a promising bariatric procedure. Tens of thousands of this procedure have been performed throughout the world since Rutledge performed the first procedure in the United States of America in 1997. Several thousands of these have even been documented in the published scientific literature. Despite a proven track record over nearly two decades, this operation continues to polarise the bariatric community. A large number of surgeons across the world have strong objections to this procedure and do not perform it. The risk of symptomatic (bile) reflux, marginal ulceration, severe malnutrition, and long-term risk of gastric and oesophageal cancers are some of the commonly voiced concerns. Despite these expressed fears, several advantages such as technical simplicity, shorter learning curve, ease of revision and reversal, non-inferior weight loss and comorbidity resolution outcomes have prompted some surgeons to advocate a wider adoption of this procedure. This review examines the current status of these controversial aspects in the light of the published academic literature in English. PMID- 27251827 TI - Is mini-laparoscopic cholecystectomy any better than the gold standard?: A comparative study. AB - BACKGROUND: Mini-laparoscopic cholecystectomy (MLC) has widened the horizons of modern laparoscopic surgery. Standard four port laparoscopic cholecystectomy (SLC), which has long been established as the "Gold Standard" for gall bladder diseases, is under reconsideration following the advent of further minimally invasive procedures including MLC. Our study aims to provide a comparison between MLC and SLC and assesses whether MLC has any added benefits. MATERIALS AND METHODS: Patients with symptomatic gall bladder disease undergoing MLC or SLC during the 2.5-month period were included in the study. Thirty-two patients underwent MLC while SLC was performed on 40 patients by the same surgeon. Data was collected prospectively and analysed retrospectively using a predesigned questionnaire. RESULTS: In our study, both the groups had similar age, body mass index (BMI) and gender distribution. No cases of MLC required insertion of additional ports. The mean operative time for MLC was 38.2 min (33-61 min), which is longer than SLC; but it was not statistically significant. There was no significant difference in mean operative blood loss, postoperative pain, analgesia requirement and mobilization. Patients who underwent MLC were able to return to normal activity earlier than patients undergoing SLC (P < 0.01). CONCLUSION: Our experience suggests that MLC can safely be used as an alternative to SLC. Compared to SLC, it has the added benefit of an early return to work along with excellent cosmetic results. Further large scale trials are required to prove any additional benefit of MLC. PMID- 27251829 TI - Anomalous middle hepatic artery in laparoscopic cholecystectomy: Wolf in sheep's clothing. AB - Laparoscopic cholecystectomy is a simple but dangerous operation. The complex anatomy and frequent anomalies of the hepatic arterial and biliary system are often a shocking surprise to the laparoscopic surgeon. When these vital structures cannot be identified correctly, potentially crippling serious vascular and biliary injury can occur. A very rare case of middle hepatic artery encountered in the Calot's coursing over the gall bladder and travelling extraparenchymal into segment IV is reported. Identification and preservation of the middle hepatic artery is essential to prevent the possibility of hepatic artery thrombosis and to avoid ischemic cholangiopathy of segment IV duct. A comprehensive understanding of the hepatic arterial and biliary anatomy of the liver will empower laparoscopic surgeons to avoid crippling vascular and biliary injury. PMID- 27251830 TI - The difficulties encountered in conversion from classic pancreaticoduodenectomy to total laparoscopic pancreaticoduodenectomy. AB - BACKGROUND: Recently, total laparoscopic pancreatectomy has been performed at many centres as an alternative to open surgery. In this study, we aimed to present the difficulties that we have encountered in converting from classic open pancreaticoduodenectomy to total laparoscopic pancreatectomy. MATERIALS AND METHODS: Between December 2012 and January 2014, we had 100 open pancreaticoduodenectomies. Subsequently, we tried to perform total laparoscopic pancreaticoduodenectomy (TLPD) in 22 patients. In 17 of these 22 patients, we carried out the total laparoscopic procedure. We analysed the difficulties that we encountered converting to TLPD in three parts: Preoperative, operative and postoperative. Preoperative difficulties involved patient selection, preparation of operative instruments, and planning the operation. Operative difficulties involved the position of the trocars, dissection, and reconstruction problems. The postoperative difficulty involved follow-up of the patient. RESULTS: According to our experiences, the most important problem is the proper selection of patients. Contrary to our previous thoughts, older patients who were in better condition were comparatively more appropriate candidates than younger patients. This is because the younger patients have generally soft pancreatic texture, which complicates the reconstruction. The main operative problems are trocar positions and maintaining the appropriate position of the camera, which requires continuous changes in its angles during the operation. However, postoperative follow-up is not very different from the classic procedure. CONCLUSION: TLPD is a suitable procedure under appropriate conditions. PMID- 27251833 TI - Laparoscopic diverticulectomy with the aid of intraoperative gastrointestinal endoscopy to treat epiphrenic diverticulum. AB - OBJECTIVE: Most researchers believe that the presence of large epiphrenic diverticulum (ED) with severe symptoms should lead to the consideration of surgical options. The choice of minimally invasive techniques and whether Heller myotomy with antireflux fundoplication should be employed after diverticulectomy became points of debate. The aim of this study was to describe how to perform laparoscopic transhiatal diverticulectomy (LTD) and oesophagomyotomy with the aid of intraoperative gastrointestinal (GI) endoscopy and how to investigate whether the oesophagomyotomy should be performed routinely after LTD. PATIENTS AND METHODS: From 2008 to 2013, 11 patients with ED underwent LTD with the aid of intraoperative GI endoscopy at our department. Before surgery, 4 patients successfully underwent oesophageal manometry: Oesophageal dysfunction and an increase of the lower oesophageal sphincter pressure (LESP) were found in 2 patients. RESULTS: There were 2 cases of conversion to an open transthoracic procedure. Six patients underwent LTD, Heller myotomy and Dor fundoplication; and 3 patients underwent only LTD. The dysphagia and regurgitation 11 patients experienced before surgery improved significantly. Motor function studies showed that there was no oesophageal peristalsis in 5 patients during follow-up, while 6 patients showed seemingly normal oesophageal motility. The LESP of 6 patients undergoing LTD, myotomy and Dor fundoplication was 16.7 +/- 10.2 mmHg, while the LESPs of 3 patients undergoing only LTD were 26 mmHg, 18 mmHg and 21 mmHg, respectively. In 4 cases experiencing LTD, myotomy and Dor fundoplication, the gastro-oesophageal reflux occurred during the sleep stage. CONCLUSIONS: LTD constitutes a safe and valid approach for ED patients with severe symptoms. As not all patients with large ED have oesophageal disorders, according to manometric and endoscopic results, surgeons can categorise and decide whether or not myotomy and antireflux surgery after LTD will be conducted. PMID- 27251835 TI - Clinical outcomes of single incision laparoscopic surgery and conventional laparoscopic transabdominal preperitoneal inguinal hernia repair. AB - BACKGROUND: Laparoscopic surgery has been a frequently performed method for inguinal hernia repair. Studies have demonstrated that the laparoscopic transabdominal preperitoneal (TAPP) approach is an appropriate choice for inguinal hernia repair. Single-incision laparoscopic surgery (SILS) was developed to improve the cosmetic effects of conventional laparoscopy. The aim of this study was to evaluate the safety and feasibility of SILS-TAPP compared with TAPP technique. MATERIALS AND METHODS: A total of 148 patients who underwent TAPP or SILS-TAPP in our surgery clinic between December 2012 and January 2015 were enrolled. Data including patient demographics, hernia characteristics, operative time, intraoperative and postoperative complications, length of hospital stay and recurrence rate were retrospectively collected. RESULTS: In total, 60 SILS-TAPP and 88 TAPP procedures were performed in the study period. The two groups were similar in terms of gender, type of hernia, and American Society of Anesthesiologists (ASA) classification score. The patients in the SILS-TAPP group were younger when compared the TAPP group. Port site hernia (PSH) rate was significantly high in the SILS-TAPP group, and all PSHs were recorded in patients with severe comorbidities. The mean operative time has no significant difference in two groups. All SILS procedures were completed successfully without conversion to conventional laparoscopy or open repair. No intraoperative complication was recorded. There was no recurrence during the mean follow-up period of 15.2 +/- 3.8 months. CONCLUSION: SILS TAPP for inguinal hernia repair seems to be a feasible, safe method, and is comparable with TAPP technique. However, randomized trials are required to evaluate long-term clinical outcomes. PMID- 27251836 TI - An unusual approach for the treatment of oesophageal perforation: Laparoscopic endoscopic cooperative surgery. AB - Boerhaave syndrome describes a transmural oesophageal rupture that develops following a spontaneous, sudden intraluminal pressure increase (i.e. vomiting, cough). It has a high rate of mortality and morbidity because of its proximity to the mediastinum and pleura. Perforation localisation and treatment initiation time affect the morbidity and mortality. In this article, we aim to present our successful laparoscopic-endoscopic cooperative surgery in a 59-year-old female who was referred to our clinic with a diagnosis of spontaneous lower oesophageal perforation. Laparoscopy and a simultaneous oesophageal stent application may be assumed as an effective alternative to conventional surgical approaches in cases of spontaneous lower oesophageal perforation. PMID- 27251837 TI - Gastric duplication cyst in adult: Challenge for surgeons. AB - Gastric duplication cysts (GDCs) are uncommon developmental anomalies found primarily in children, being rarely seen in adults. Duplications can occur anywhere in the intestinal tract from the mouth to the anus. Accurate diagnosis of cysts before resection is difficult even using the most advanced imaging techniques. In this report, we present and discuss a case of GDC in a 25-year-old man treated laparoscopically. Patient admitted to our department with complaints of epigastric pain and swelling. Magnetic resonance imaging performed for accurate characterisation showed a 4 cm * 4.5 cm cystic lesion, with heterogeneous signal intensity on T2-weighted images, located in the posterior wall of the stomach. Pre-operative differential diagnosis including gastrointestinal stromal tumour (GIST) was made according to radiological findings. Patient underwent surgery and cyst resected laparoscopically. Histopathological examination suggesting duplication cyst. GDC can easily be mistaken for a GIST, and the clinician as well as radiologist must maintain a high degree of suspicion. PMID- 27251838 TI - Laparoscopic excision of a large retroperitoneal lymphovascular malformation in an adult. AB - Retroperitoneal lymphangioma is a rare benign tumour of the retroperitoneal lymphatics that usually manifests in infancy. It is worth reporting of an unexpected presentation, especially in an adult. They frequently affect the neck (75%) and the axilla (20%). Intra-abdominal lymphangiomas (<5%) have been reported in the mesentery, gastrointestinal tract, spleen, liver and pancreas. Retroperitoneal lymphangiomas account for nearly 1% of all lymphangiomas and are uncommon incidental findings usually at surgery, autopsy or lymphography. Differentiating cystic lymphangiomas from other cystic growths by imaging studies alone is often inconclusive, and surgery is frequently required for definitive diagnosis. An interesting and rare case of a retroperitoneal lymphangioma in an adult patient which was removed laparoscopically is described here. PMID- 27251839 TI - Complication reports for robotic surgery using three arms by a single surgeon at a single institution. AB - BACKGROUND: The aim of this study is to evaluate perioperative complications related to robotic-assisted laparoscopic surgery for management of gynaecologic disorders. MATERIALS AND METHODS: Eight hundred and fifty-one women who underwent robotic procedures between December 2011 and April 2015 were retrospectively included for analysis. Patient demographics, surgical outcomes and complications were evaluated. RESULTS: The overall complication rate was 5.5%, whereas the rate of complications for oncologic cases was 8.4%. Intra-operative complications (n = 7, 0.8%) consisted of five cases of bowel lacerations, one case of ureter laceration and one case of bladder injury. Early and late post-operative complications were 4.0% (n = 34) and 0.8% (n = 6), respectively. Six patients (0.7%) experienced Grade III complications based on the Clavien-Dindo classification and required further surgical intervention. CONCLUSION: Robotic assisted laparoscopic surgery is a feasible approach for management of gynaecologic disorders; the complication rates for this type of procedure are acceptable. PMID- 27251840 TI - Laparoscopic adrenalectomy in a patient with situs inversus totalis. AB - Situs inversus totalis(SIT) is a relatively rare condition involving transposition of both the abdominal and thoracic viscera. SIT typically presents as left to right reversal of the viscera combined with dextrocardia, while the individual organs function is normal. Although there are no obvious abnormalities in the function of transposed organs, anatomical irregularity causes important technical difficulties in the surgical treatment of these patients. In this study, we aim to report surgical challenges in laparoscopic adrenalectomy in a patient with SIT. PMID- 27251841 TI - Laparoscopic versus percutaneous endoscopic gastrostomy placement in children: Results of a systematic review and meta-analysis. AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) and laparoscopic-assisted gastrostomy (LAG) are widely used in the paediatric population. The aim of this study was to determine which one of the two procedures is the most effective and safe method. METHODS: This systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analyses statement. Primary outcomes were success rate, efficacy of feeding, quality of life, gastroesophageal reflux and post-operative complications. RESULTS: Five retrospective studies, comparing 550 PEG to 483 LAG placements in children, were identified after screening 2347 articles. The completion rate was similar for both procedures. PEG was associated with significantly more adjacent bowel injuries (P = 0.047), early tube dislodgements (P = 0.02) and complications that require reintervention under general anaesthesia (P < 0.001). Minor complications were equally frequent after both procedures. CONCLUSIONS: Because of the lack of well-designed studies, we have to be cautious in making definitive conclusions comparing PEG to LAG. To decide which type of gastrostomy placement is best practice in paediatric patients, randomised controlled trials comparing PEG to LAG are highly warranted. PMID- 27251842 TI - Laparoscopy in children and its impact on brain oxygenation during routine inguinal hernia repair. AB - BACKGROUND: The systemic impact of intra-abdominal pressure (IAP) and/or changes in carbon dioxide (CO2) during laparoscopy are not yet well defined. Changes in brain oxygenation have been reported as a possible cause of cerebral hypotension and perfusion. The side effects of anaesthesia could also be involved in these changes, especially in children. To date, no data have been reported on brain oxygenation during routine laparoscopy in paediatric patients. PATIENTS AND METHODS: Brain and peripheral oxygenation were investigated in 10 children (8 male, 2 female) who underwent elective minimally invasive surgery for inguinal hernia repair. Intraoperative transcranial near-infrared spectroscopy to assess regional cerebral oxygen saturation (rScO2), peripheral oxygen saturation using pulse oximetry and heart rate (HR) were monitored at five surgical intervals: Induction of anaesthesia (baseline T1); before CO2insufflation induced pneumoperitoneum (PP) (T2); CO2PP insufflation (T3); cessation of CO2PP (T4); before extubation (T5). RESULTS: rScO2decreases were recorded immediately after T1 and became significant after insufflation (P = 0.006; rScO2decreased 3.6 +/- 0.38%); restoration of rScO2was achieved after PP cessation (P = 0.007). The changes in rScO2were primarily due to IAP increases (P = 0.06). The HR changes were correlated to PP pressure (P < 0.001) and CO2flow rate (P = 0.001). No significant peripheral effects were noted. CONCLUSIONS: The increase in IAP is a critical determinant in cerebral oxygenation stability during laparoscopic procedures. However, the impact of anaesthesia on adaptive changes should not be underestimated. Close monitoring and close collaboration between the members of the multidisciplinary paediatric team are essential to guarantee the patient's safety during minimally invasive surgical procedures. PMID- 27251843 TI - Intra-cholecystic approach for laparoscopic management of Mirizzi's syndrome: A case series. AB - INTRODUCTION: Laparoscopic management of patients with Mirizzi's syndrome (MS) is not routinely recommended due to the high risk of iatrogenic complications. PATIENTS AND METHODS: Intra-cholecystic (IC) or inside-gall bladder (GB) approach was used for laparoscopic management of 16 patients with MS at a tertiary care referral centre in North India from May 2010 to August 2014; a retrospective analysis of prospectively collected data was performed. RESULTS: Mean age was 40.1 +/- 14.7 years, the male-to-female ratio was 1:3, and 9 (56.25%) patients had type 1 MS (MS1) and 7 (43.75%) had type 2 MS (MS2) (McSherry's classification). The laparoscopic intra-cholecystic approach (LICA) was successful in 11 (68.75%) patients, whereas 5 patients (31.25%) required conversion to open method. Median blood loss was 100 mL (range: 50-400 mL), and median duration of surgery was 3.25 h (range: 2-7.5 h). No major complications were encountered except 1 patient (6.5%) who required re-operation for retained bile duct stones. The final histopathology report was benign in all the patients. No remote complications were noted during a mean follow-up of 20.18 months. CONCLUSION: LICA is a feasible and safe approach for selected patients with Mirizzi's syndrome; however, a low threshold for conversion is necessary to avoid iatrogenic complications. PMID- 27251844 TI - Comparison of short outcomes between laparoscopic and experienced robotic gastrectomy: A meta-analysis and systematic review. AB - OBJECTIVE: The purpose of this meta-analysis is to compare the short-term outcomes between experienced robotic gastrectomy (RG) and laparoscopic gastrectomy (LG). MATERIALS AND METHODS: We searched the PubMed, Springer Link, Elsevier, and Embase databases for articles published in English before June 2015 using an electronic literature search and including cross-referenced articles. Three studies were eligible for the meta-analysis. The outcomes evaluated were operation time, estimated blood loss, harvested lymph nodes, complication, and postoperative hospital stay. RESULTS: Of a total of 562 patients, 165 underwent RG and 397 underwent LG. Operation time was significantly longer in the RG group [weighted mean difference (WMD): 21.49, 95% confidence interval (CI): 12.48 30.50, P< 0.00001). Estimated blood loss, harvested lymph nodes, complication, and postoperative hospital stay were similar between the two groups. CONCLUSION: Experienced RG has similar short-term outcomes to LG that is performed by sophisticated laparoscopic surgeons, except for operation time. PMID- 27251845 TI - Use of a novel multi-purpose sponge for laparoscopic surgery: Does it have special relevance to robotically-assisted laparoscopic surgery? AB - BACKGROUND: The STAR System (Ekymed SpA) is a novel multipurpose sponge developed for conventional manual laparoscopic surgery. MATERIALS AND METHODS: Between December 2012 and December 2014, we successfully used the sponge in ten robot assisted and ten direct manual laparoscopic operations to achieve haemostasis, for blunt dissections, for atraumatic lifting of solid organs, to check for bile leaks, for cleaning the surgical field thus avoiding frequent use of suction or the application of haemostatic agents. The reason of the insertion (RI), the main use (MU) and any further use (FU), once inserted, were registered for each operation and compared between the two groups. RESULTS: The principal RI was haemostasis for minor bleeding, without differences between the two groups (P = not significant). Regard to MU, in the robotic group cleaning the surgical field was utilised more than laparoscopic group (100% vs. 60%; P = 0.03). About FU, atraumatic solid organs lifting was more frequent during robotically assisted surgery than with laparoscopy (50% vs. 0%; P = 0.01). A statistically more frequent use of the sponge was registered during standard laparoscopy for the blunt dissection (30% vs. 80%; P = 0.03). CONCLUSIONS: The STAR System was beneficial in both approaches, but it imparts added benefit during robotically assisted laparoscopic surgery organs because of the lack of tactile feedback and because the operating surgeon is remote from the patient, and has to rely on the assisting surgeon in the sterile field for dealing with bleeding episodes, cleansing/mopping the operative field when necessary, who may not be experienced or completely proficient. PMID- 27251846 TI - Laparoscopic side-to-side pancreaticojejunostomy for chronic pancreatitis in children. AB - Surgical pancreatic duct (PD) drainage for chronic pancreatitis in children is relatively rare. It is indicated in cases of recurrent pancreatitis and PD dilatation that have not responded to medical therapy and therapeutic endoscopy. We performed laparoscopic side-to-side pancreaticojejunostomy for two paediatric patients with chronic pancreatitis. The main PD was opened easily by electrocautery after locating the dilated PD by intraoperative ultrasonography. The dilated PD was split longitudinally from the pancreatic tail to the pancreatic head by laparoscopic coagulation shears or electrocautery after pancreatography. A laparoscopic side-to-side pancreaticojejunostomy was performed by a one-layered technique using continuous 4-0 polydioxanone (PDS) sutures from the pancreatic tail to the pancreatic head. There were no intraoperative or postoperative complications or recurrences. This procedure has cosmetic advantages compared with open surgery for chronic pancreatitis. Laparoscopic side to-side pancreaticojejunostomy in children is feasible and effective for the treatment of chronic pancreatitis. PMID- 27251847 TI - Perforated Meckel's diverticulum containing a carcinoid tumor successfully treated by the laparoscopic approach: Case report. AB - Mekel's diverticulum is a gastrointestinal malformation. Occurs in one of every 40 patients. It is usually asymptomatic whereas complications can be developed in 2% to 4%. The report is based on a 41-year old male, who attended to emergency, complaining of right lower quadrant abdominal pain. Blood tests showed high level of inflammatory markers. With acute appendicitis as presumptive diagnosis, laparoscopy was performed. The intraoperative findings were: a perforated Mekel's diverticulum with normal cecal appendix. Mechanical diverticular resection was made. The patient was successfully recovered from surgery. Histopathology examination showed: Meckel's diverticulum perforated with acute inflammation and neuroendocrine tumor (G1) pT1. Mekel's diverticulum is rarely affected by inflammatory complications and just few cases are associated with tumors. However, has ever been described before, coexisting both situations, being our patient the first reported with this exceptional clinical presentation, and treated successfully by laparoscopic approach. PMID- 27251848 TI - GSK2656157, a PERK inhibitor, reduced LPS-induced IL-1beta production through inhibiting Caspase 1 activation in macrophage-like J774.1 cells. AB - IL-1beta is one of the inflammatory cytokines and is cleaved from pro-IL-1beta proteolytically by activated Caspase 1. For the activation of Caspase 1, inflammasome was formed by two signals, what is called, priming and triggering signals. In this study, it was found that mouse macrophage J774.1 cells, when treated by single large amount of lipopolysaccharide (LPS), produced a significant amount of IL-1beta. On the other hand, IL-1beta production was not detected when treated by a single, small amount of LPS. Then, focusing on endoplasmic reticulum (ER) stress response among stress responses induced by a large amount of LPS, when GSK2656157, a PERK inhibitor, was used for inhibition of ER stress, GSK2656157 reduced IL-1beta production dose-dependently. Next, when Thapsigargin, an ER stress reagent, was added with LPS, IL-1beta production increased more than by LPS alone. Thus, these results suggested that ER stress was involved in LPS-induced IL-1beta production. When the activation of Caspase 1 was examined by fluorescence activated cell sorter analysis, it was found that GSK2656157 inhibited LPS-induced Caspase 1 activation. Further, it was confirmed that GSK2656157 did not affect LPS-induced TNF-alpha production and activation of NF-kappaB and specifically inhibited the PERK/eIF-2alpha pathway. Therefore, it was found that GSK2656157 specifically inhibited ER stress induced by large amount of LPS and reduced LPS-induced IL-1beta production through inhibition of Caspase 1 activation. PMID- 27251849 TI - Cannulation Selection of Portal Venous and Splenic Venous Catheterization in Venovenous Bypass of Swine Orthotopic Liver Transplantation. AB - BACKGROUND The aim of this study was to compare the hemodynamic changes in 2 different cannulations in portal system (portal venous catheterization and splenic venous catheterization) during venovenous bypass (VVB) of swine orthotopic liver transplantation (OLT) MATERIAL AND METHODS Thirty pairs (a total of 60) of healthy Duroc pigs were selected for OLT. According to the difference of cannulation in portal venous system during VVB, these pigs were divided into 2 groups: the PVC group (pigs with portal venous catheterization, n=15) and the SVC group (pigs with splenic venous catheterization, n=15). Intraoperative hemodynamic parameters were monitored continuously. RESULTS Two recipients in the PVC group died: 1 died of unsmooth bypass during the operation and 1 died of disseminated intravascular coagulation (DIC). There was only 1 death in the SVC group, due to hemorrhagic shock. The duration of anhepatic phase (AP) in the SVC group was significantly shorter than in the PVC group (P<0.05). Moreover, hemodynamic parameters in phase III (5 min after start of portal vein suturing) and phase IV (5 min after graft reperfusion) were remarkably different between the SVC group and the PVC group (P<0.05). CONCLUSIONS Our results show that VVB via splenic venous catheterization in swine OLT: 1) shortens the AP time; 2) keeps the hemodynamics stable; and 3) reduces the occurrence of postoperative complications. Thus, SVC appears to be superior to PVC. PMID- 27251850 TI - MLX Is a Transcriptional Repressor of the Mammalian Golgi Stress Response. AB - The Golgi stress response is a homeostatic mechanism that controls the capacity of the Golgi apparatus in accordance with cellular demands. When the capacity of the Golgi apparatus becomes insufficient (Golgi stress), transcription levels of Golgi-related genes encoding glycosylation enzymes, a Golgi structural protein, and components of vesicular transport are upregulated through a common cis-acting enhancer-the Golgi apparatus stress response element (GASE). Here, we identified the transcription factor MLX as a GASE-binding protein. MLX resides in the cytoplasm and does not bind to GASE in normal growth conditions, whereas MLX translocates into the nucleus and specifically binds to GASE in response to Golgi stress. Suppression of MLX expression increased transcriptional induction of target genes of the Golgi stress response, whereas overexpression of MLX reduced GASE-binding of TFE3 as well as transcriptional induction from GASE, suggesting that MLX is a transcriptional repressor of the mammalian Golgi stress response. PMID- 27251852 TI - Analytical tools for the analysis of fire debris. A review: 2008-2015. AB - The analysis of fire debris evidence might offer crucial information to a forensic investigation, when for instance, there is suspicion of the intentional use of ignitable liquids to initiate a fire. Although the evidence analysis in the laboratory is mainly conducted by a handful of well-established methodologies, during the last eight years several authors proposed noteworthy improvements on these methodologies, suggesting new interesting approaches. This review critically outlines the most up-to-date and suitable tools for the analysis and interpretation of fire debris evidence. The survey about analytical tools covers works published in the 2008-2015 period. It includes sources of consensus-classified reference samples, current standard procedures, new proposals for sample extraction and analysis, and the most novel statistical tools. In addition, this review provides relevant knowledge on the distortion effects of the ignitable liquid chemical fingerprints, which have to be considered during interpretation of results. PMID- 27251851 TI - Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono- and Dimethyl Ethers. AB - The study of chemistry of naturally occurring compounds and the synthesis of their derivatives is fundamentally important for the development of new drugs. In this work, dehydrodieugenol (DHDE) was obtained through oxidative coupling of eugenol, promoted by an aqueous mixture of potassium ferricyanide (K3 [Fe(CN)6 ]) and NH3 . H2 O. The partial methoxylation of DHDE with MeI and K2 CO3 mainly resulted in the molecular-shaped monomethyl ether (DHDE-1MeO) and its dimethyl ether derivative (DHDE-2MeO). The products from the reactions were characterized by (1) H- and (13) C-NMR spectroscopy. Additionally, these studies have reported the antileishmanial activity of DHDE against Leishmania amazonensis (IC50 value of 42.20 MUg ml(-1) ) and shown that partial methoxylation of DHDE results in a significant increase in its antiparasitic activity (IC50 value of 13.68 MUg ml( 1) ). Based on in vitro bioassays, DHDE-1MeO has shown the highest leishmanicidal activity in promastigota form. Production by direct one-step synthesis of this monomethoxylated compound can be considered to be a cost-effective and environmentally friendly method with a short reaction time. PMID- 27251853 TI - Synchrotron radiation-based multi-analytical approach for studying underglaze color: The microstructure of Chinese Qinghua blue decors (Ming dynasty). AB - In this paper, we develop a methodological approach combining macro-X-ray fluorescence and synchrotron radiation-based techniques (MUXRF, full-field XANES and MUXRD) to determine the composition and microstructure of underglaze decors of Qinghua porcelains (Ming dynasty). Various transition metal elements (Fe, Mn, Co) are present in the blue decoration of these ceramics and the approach proposed allows for establishing the feature of each. Thus it shows that Fe ions are distributed homogeneously over the whole glaze without any significant difference in blue and white parts. They do not play a significant role in the color. In contrast, Co ions exhibit a heterogeneous distribution with CoAl2O4 particles close to the body/glaze interphase. These particles play a key role in the blue color and, the hue variations seem in greater part to link to their density and repartition. Co dispersed in the glassy matrix is also bivalent and mainly in tetragonal coordination, leading also to a blue color. Mn ion distribution is similar to the one of Co but without presenting local high concentrations associated to Mn based particles. Mn affects the darkness of the color and for the sample without CoAl2O4 particle; it is the main color contribution. The presence of CoAl2O4 crystals was confirmed by MUXRD, which revealed, in addition, a variation of cell parameters certainly linking to a Co partial substitution. PMID- 27251854 TI - Fast analysis of terbutaline in pharmaceuticals using multi-walled nanotubes modified electrodes from recordable compact disc. AB - In this study, homemade disposable gold electrodes made from recordable compact disks were modified with carbon nanotubes for amperometric quantification of terbutaline sulfate in pharmaceutical products. A flow cell using an impingent jet of solution on the electrode surface was build and used for amperometric detection, and a series of experiments were carried out to find the best experimental conditions for the new electrode in a specially designed cell. A linear response for terbutaline was obtained in the range from 3.0 * 10(-6) to 5.0 * 10(-4) mol L(-1) (at 0.63 V vs. Ag/AgCl). The limits of detection and quantification were calculated as 5.8 * 10(-7) mol L(-1) (S/N = 3) and 1.9 * 10( 6) mol L(-1) (S/N = 10), respectively. A frequency of 30 injections h(-1) was attained. The proposed method was successfully applied to the analyses of commercial syrup samples, and all results were in good agreement with those obtained by using high performance liquid chromatography and capillary electrophoresis-tandem mass spectrometry. PMID- 27251855 TI - Band-type microelectrodes for amperometric immunoassays. AB - A band-type microelectrode was made using a parylene-N film as a passivation layer. A circular-type, mm-scale electrode with the same diameter as the band type microelectrode was also made with an electrode area that was 5000 times larger than the band-type microelectrode. By comparing the amperometric signals of 3,5,3',5'-tetramethylbenzidine (TMB) samples at different optical density (OD) values, the band-type microelectrode was determined to be 9 times more sensitive than the circular-type electrode. The properties of the circular-type and the band-type electrodes (e.g., the shape of their cyclic voltammograms, the type of diffusion layer used, and the diffusion layer thickness per unit electrode area) were characterized according to their electrode area using the COMSOL Multiphysics software. From these simulations, the band-type electrode was estimated to have the conventional microelectrode properties, even when the electrode area was 100 times larger than a conventional circular-type electrode. These results show that both the geometry and the area of an electrode can influence the properties of the electrode. Finally, amperometric analysis based on a band-type electrode was applied to commercial ELISA kits to analyze human hepatitis B surface antigen (hHBsAg) and human immunodeficiency virus (HIV) antibodies. PMID- 27251856 TI - Children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. AB - This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. PMID- 27251857 TI - Influence of chitosan coating on magnetic nanoparticles in endothelial cells and acute tissue biodistribution. AB - Chitosan coating on magnetic nanoparticles (MNPs) was studied on biological systems as a first step toward the application in the biomedical field as drug targeted nanosystems. Composition of MNPs consists of magnetite functionalized with oleic acid and coated with the biopolymer chitosan or glutaraldehyde-cross linked chitosan. The influence of the biopolymeric coating has been evaluated by in vitro and in vivo assays on the effects of these MNPs on rat aortic endothelial cells (ECs) viability and on the random tissue distribution in mice. Results were correlated with the physicochemical properties of the nanoparticles. Nitric oxide (NO) production by ECs was determined, considering that endothelial NO represents one of the major markers of ECs function. Cell viability was studied by MTT assay. Different doses of the MNPs (1, 10 and 100 MUg/mL) were assayed, revealing that MNPs coated with non-cross-linked chitosan for 6 and 24 h did not affect neither NO production nor cell viability. However, a significant decrease in cell viability was observed after 36 h treatment with the highest dose of this nanocarrier. It was also revealed that the presence and dose of glutaraldehyde in the MNPs structureimpact on the cytotoxicity. The study of the acute tissue distribution was performed acutely in mice after 24 h of an intraperitoneal injection of the MNPs and sub acutely, after 28 days of weekly administration. Both formulations greatly avoided the initial clearance by the reticuloendothelial system (RES) in liver. Biological properties found for N1 and N2 in the performed assays reveal that chitosan coating improves biocompatibility of MNPs turning these magnetic nanosystems as promising devices for targeted drug delivery. PMID- 27251859 TI - The definition and diagnosis of developmental prosopagnosia. AB - Over the last 20 years much attention in the field of face recognition has been directed towards the study of developmental prosopagnosia (DP), with some authors investigating the behavioural characteristics of the condition, and many others using these individuals to further our theoretical understanding of the typical face-processing system. It is broadly agreed that the term "DP" refers to people who have failed to develop the ability to recognize faces in the absence of neurological illness or injury, yet more precise terminology in relation to potential subtypes of the population are yet to be confirmed. Furthermore, specific diagnostic techniques and inclusion and exclusion criteria have yet to be uniformly accepted across the field, making cross-paper comparisons and meta analyses very difficult. This paper presents an overview of the current challenges that face research into DP and introduces a series of papers that attempt to further our understanding of the condition's characteristics. It is hoped that this special issue will provide a springboard for further research addressing these issues, improving the current state of the art by ensuring the quality of theoretical investigations into DP, and by posing advances that will assist those who have the condition. PMID- 27251858 TI - Anomalous uptake and circulatory characteristics of the plant-based small RNA MIR2911. AB - Inconsistent detection of plant-based dietary small RNAs in circulation has thwarted the use of dietary RNA therapeutics. Here we demonstrate mice consuming diets rich in vegetables displayed enhanced serum levels of the plant specific small RNA MIR2911. Differential centrifugation, size-exclusion chromatography, and proteinase K treatment of plant extracts suggest this RNA resides within a proteinase K-sensitive complex. Plant derived MIR2911 was more bioavailable than the synthetic RNA. Furthermore, MIR2911 exhibited unusual digestive stability compared with other synthetic plant microRNAs. The characteristics of circulating MIR2911 were also unusual as it was not associated with exosomes and fractionated as a soluble complex that was insensitive to proteinase K treatment, consistent with MIR2911 being stabilized by modifications conferred by the host. These results indicate that intrinsic stability and plant-based modifications orchestrate consumer uptake of this anomalous plant based small RNA and invite revisiting plant-based microRNA therapeutic approaches. PMID- 27251861 TI - Strategic cooperation with WHO. PMID- 27251860 TI - Solvent-induced multicolour fluorescence of amino-substituted 2,3-naphthalimides studied by fluorescence and transient absorption measurements. AB - A series of amino-2,3-naphthalimide derivatives having the amino functionality at 1-, 5- and 6-positions (, and , respectively) were prepared, and their photophysical properties were systematically investigated based on the measurements of steady-state absorption and fluorescence spectra, fluorescence lifetimes as well as transient absorption spectra. The s efficiently fluoresced in solution, and the emission spectra appreciably shifted depending on the solvent polarity. displayed only a slight fluorescence red-shift upon increasing the solvent polarity. In contrast, and showed marked positive solvatofluorochromism with large Stokes shifts displaying multicolour fluorescence; the fluorescence colours of and varied from violet-blue in hexane to orange-red in methanol. and , thus, serve as micro-environment responding fluorophores. In methanol, the intensity of the fluorescence emission band of and significantly reduced. Based on the fluorescence quantum yields and lifetimes, and transient absorption measurements, it has been revealed that internal conversion from the S1 state of s to the ground state was accelerated by the protic medium, resulting in a reduction in their fluorescence efficiency, while intersystem crossing from the S1 state to a triplet state was not responsible for the decrease of fluorescence intensity. PMID- 27251862 TI - Elevated periostin in serum and peritoneal washing fluids as potential biomarkers for endometriosis. AB - BACKGROUND: To identify the level of periostin in serum and peritoneal washing fluids (PWF) from women with and without endometriosis, as well as to explore the potential of periostin as a biomarker of endometriosis. METHODS: Samples were obtained from 184 women with and without endometriosis. Concentrations of periostin in PWF and blood were measured by enzyme-linked immunosorbent assay. RESULTS: Levels of periostin both in serum and PWF were notably elevated in women with endometriosis in both the proliferative and secretory phase. Combined with dysmenorrhea and infertility, two potential covariates, the serum periostin had a sensitivity of 75.00%, specificity of 65.00%, and area under the curve (AUC) of 0.774, whereas the PWF periostin had a sensitivity of 94.23%, specificity of 90.00%, and AUC of 0.967 for the diagnosis of endometriosis. CONCLUSION: Serum and PWF periostin concentrations may be new potential biomarkers for endometriosis, especially when combined with dysmenorrhea and infertility. PMID- 27251863 TI - Inhibition of Osteoclast Differentiation and Bone Resorption by Bisphosphonate conjugated Gold Nanoparticles. AB - In recent years, gold nanoparticles (GNPs) have been reported to affect the regeneration of bone tissue. The goal of this study was to improve bone tissue regeneration by using targeted GNPs. We fabricated a functionalized GNPs conjugated with alendronate (ALD), of the bisphosphonate group. Subsequently, the ALD, GNPs, and ALD conjugated GNPs (GNPs-ALD) were analyzed by ultraviolet visible absorbance (UV-vis) spectrophotometer, Attenuated total reflectance Fourier transform infrared spectrometer (ATR-FTIR), and thermo gravimetric analysis (TGA). The prepared GNPs-ALD were used to investigate their inhibitory effects on the receptor activator of nuclear factor- kappab ligand (RANKL) induced osteoclastogenesis in bone marrow-derived macrophages (BMMs). Additionally, the GNPs-ALD were applied to ovariectomy (OVX)-induced osteoporotic mice and the experiments were evaluated. ALD was found to be successfully conjugated to the GNPs surface, and it displayed significant adhesion onto the bone surface. The in-vitro study indicated that the GNPs, ALD and GNPs-ALD suppressed osteoclast formation in a dose-dependent manner. Furthermore, in the OVX mouse model, the mice treated GNPs-ALD had higher bone density as compared to other OVX mice groups. The results from these tests indicated that GNPs-ALD can be useful agents for preventing and treating osteoporosis. PMID- 27251864 TI - Rol genes enhance the biosynthesis of antioxidants in Artemisia carvifolia Buch. AB - BACKGROUND: The secondary metabolites of the Artemisia genus are well known for their important therapeutic properties. This genus is one of the valuable sources of flavonoids and other polyphenols, but due to the low contents of these important metabolites, there is a need to either enhance their concentration in the original plant or seek alternative sources for them. The aim of the current study was to detect and enhance the yield of antioxidant compounds of Artemisia carvifolia Buch. HPLC analysis was performed to detect the antioxidants. With the aim of increasing flavonoid content, Rol gene transgenics of A. carvifolia were established. Two genes of the flavonoid biosynthetic pathway, phenylalanine ammonia-lyase and chalcone synthase, were studied by real time qPCR. Antioxidant potential was determined by performing different antioxidant assays. RESULTS: HPLC analysis of wild-type A. carvifolia revealed the presence of flavonoids such as caffeic acid (30 MUg/g DW), quercetin (10 MUg/g DW), isoquercetin (400 MUg/g DW) and rutin (300 MUg/g DW). Compared to the untransformed plants, flavonoid levels increased 1.9-6-fold and 1.6-4-fold in rol B and rol C transgenics, respectively. RT qPCR analysis showed a variable expression of the flavonoid biosynthetic genes, including those encoding phenylalanine ammonia-lyase and chalcone synthase, which were found to be relatively more expressed in transformed than wild-type plants, thus correlating with the metabolite concentration. Methanolic extracts of transgenics showed higher antioxidant capacity, reducing power, and protection against free radical-induced DNA damage. Among the transgenic plants, those harboring rol B were slightly more active than the rol C-transformants. CONCLUSION: As well as demonstrating the effectiveness of rol genes in inducing plant secondary metabolism, this study provides insight into the molecular dynamics of the flavonoid accumulation pattern, which correlated with the expression of biosynthetic genes. PMID- 27251867 TI - The National Children's Study: An Introduction and Historical Overview. AB - The National Children's Study (NCS) was an ambitious attempt to map children's health and development in a large representative group of children in the United States. In this introduction, we briefly review the background of the NCS and the history of the multiple strategies that were tested to recruit women and children. Subsequent articles then detail the protocols and outcomes of 4 of the recruitment strategies. It is hoped that lessons learned from these attempts to define a study protocol that could achieve the initial aims of the NCS will inform future efforts to conceptualize and execute strategies to provide generalizable insights on the longitudinal health of our nation's children. PMID- 27251865 TI - Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis. AB - Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl's gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID- 27251868 TI - The National Children's Study: Recruitment Outcomes Using an Enhanced Household Based Approach. AB - OBJECTIVES: Ten National Children's Study (NCS) study locations with diverse demographic characteristics used an enhanced household-based recruitment (EHBR) approach to enroll preconceptional and pregnant women. Study centers used different types and dosages of community outreach and engagement (COE) activities and supplemental strategies. The goal of the study was to determine whether variability in enumeration and recruitment outcomes correlated with study location characteristics or types and dosages of COE activities (number of COE events, number of advance household mailings, total media expenditures, and total COE expenditures). METHODS: Each of the sites provided data on COE activities, protocol implementation, supplemental recruitment activities, location demographic characteristics, and enumeration/recruitment outcomes. RESULTS: COE activities varied across sites in breadth and scope. Numerous strategies were used, including media advertising, social media, participation in community-wide events, presentations to stakeholders, and creation of advisory boards. Some sites included supplemental recruitment efforts. EHBR sites enrolled 1404 women at the initial pregnancy screening. No significant relationships were found between study location demographic characteristics or between the types and dosages of COE activities and recruitment outcomes. CONCLUSIONS: Probability sampling for a long-term study requires a positive image with stakeholders and within communities; this requirement may be especially true for door-to-door recruitment. EHBR sites successfully recruited a representative sample of preconceptional and pregnant women. Sites reported implementing similar COE activities but with varying dosage and cost; however, analyses did not support a benefit of COE strategies on study recruitment. PMID- 27251869 TI - The National Children's Study: Early Recruitment Outcomes Using the Direct Outreach Approach. AB - OBJECTIVE: In 2009, the National Children's Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment by using a birth rate probability sample. In 2010, the NCS Program Office launched 3 alternative recruitment methods. We tested whether direct outreach (DO) recruitment could be a more efficient strategy to recruit women of child-bearing age. METHODS: The NCS DO recruitment approach recruited women, 18 to 49 years, who were pregnant or trying to conceive using passive recruitment methods emphasizing broad community outreach and engagement to create study awareness. Study mailings to listed households included a pregnancy screening questionnaire to identify potentially eligible women from selected neighborhoods to contact the study center. Unique features of this recruitment approach included the following: (1) expansion of selected neighborhoods to maximize potential participant recruitment and enrollment while minimizing in-person participant contact and (2) offering 2 levels of study participation distinguished by data collection intensity. RESULTS: Ten study centers listed 255 475 geographically eligible households for contact representing, on average, 3.3% of households per Primary Sampling Unit. A total of 19 354 women were identified for screening, and 17 421 completed a pregnancy screener representing 6.8% of eligible households. Study-eligible pregnant women were older, more educated, and less likely to be Hispanic than the general population. Only 16% (2786) of 17 421 screened women were study-eligible, and 81.1% of these 2786 women consented to participate. CONCLUSIONS: Although feasible, the DO approach recruited a sample of study eligible pregnant women significantly different from the population. This recruitment approach was labor intensive for the yield of enrolled women. PMID- 27251870 TI - The National Children's Study: Recruitment Outcomes Using the Provider-Based Recruitment Approach. AB - OBJECTIVE: In 2009, the National Children's Study (NCS) Vanguard Study tested the feasibility of household-based recruitment and participant enrollment using a birth-rate probability sample. In 2010, the NCS Program Office launched 3 additional recruitment approaches. We tested whether provider-based recruitment could improve recruitment outcomes compared with household-based recruitment. METHODS: The NCS aimed to recruit 18- to 49-year-old women who were pregnant or at risk for becoming pregnant who lived in designated geographic segments within primary sampling units, generally counties. Using provider-based recruitment, 10 study centers engaged providers to enroll eligible participants at their practice. Recruitment models used different levels of provider engagement (full, intermediate, information-only). RESULTS: The percentage of eligible women per county ranged from 1.5% to 57.3%. Across the centers, 3371 potential participants were approached for screening, 3459 (92%) were screened and 1479 were eligible (43%). Of those 1181 (80.0%) gave consent and 1008 (94%) were retained until delivery. Recruited participants were generally representative of the county population. CONCLUSIONS: Provider-based recruitment was successful in recruiting NCS participants. Challenges included time-intensity of engaging the clinical practices, differential willingness of providers to participate, and necessary reliance on providers for participant identification. The vast majority of practices cooperated to some degree. Recruitment from obstetric practices is an effective means of obtaining a representative sample. PMID- 27251871 TI - Multilevel Provider-Based Sampling for Recruitment of Pregnant Women and Mother Newborn Dyads. AB - OBJECTIVE: In 2010, the National Children's Study launched 3 alternative recruitment methods to test possible improvements in efficiency compared with traditional household-based recruitment and participant enrollment. In 2012, a fourth method, provider-based sampling (PBS), tested a probability-based sampling of prenatal provider locations supplemented by a second cohort of neonates born at a convenience sample of maternity hospitals. METHODS: From a sampling frame of 472 prenatal care provider locations and 59 maternity hospitals, 49 provider and 7 hospital locations within or just outside 3 counties participated in study recruitment. During first prenatal care visits or immediately postdelivery at these locations, face-to-face contact was used to screen and recruit eligible women. RESULTS: Of 1450 screened women, 1270 were eligible. Consent rates at prenatal provider locations (62%-74% by county) were similar to those at birth locations (64%-77% by county). During 6 field months, 3 study centers enrolled a total prenatal cohort of 530 women (the majority in the first trimester) and during 2 months enrolled a birth cohort of an additional 320 mother-newborn dyads. As personnel became experienced in the field, the time required to enroll a woman in the prenatal cohort declined from up to 200 hours to 50 to 100 hours per woman recruited. CONCLUSIONS: We demonstrated that PBS was feasible and operationally efficient in recruiting a representative cohort of newborns from 3 diverse US counties. Our findings suggest that PBS is a practical approach to recruit large pregnancy and birth cohorts across the United States. PMID- 27251872 TI - The Experience of Direct Outreach Recruitment in the National Children's Study. AB - OBJECTIVE: Few studies have reported the outcome of direct outreach methods for recruitment of research participants in population-based samples. We describe the relationship of outreach strategies that are tailored to specific community factors to recruitment and consent outcomes in 10 National Children's Study direct outreach study locations (all were single counties). METHODS: Each study center collected data from a target population of women who resided in selected county segments that were sampled based on a geographic area probability sampling design. Based on county characteristics of the 10 study locations, each study center used site-specific marketing approaches (direct mail, mass media, provider referrals, social networking) to recruit study participants. Recruitment success was measured by the number of recruited women as well as by a qualitative assessment of the effectiveness of various recruitment methods. RESULTS: The number of women who consented varied from 67 to 792. The majority of women were pregnant at the time of consent. Community awareness varied from <1% to 70%. Although no significant associations were found between community characteristics and recruitment success, we found that certain types of outreach strategies enhanced recruitment. CONCLUSIONS: In a small sample of 10 US counties, recruitment success was not associated with community characteristics. It was, however, associated with certain types of outreach strategies that may be more effective in close-knit communities. PMID- 27251873 TI - Shifting El Nino inhibits summer Arctic warming and Arctic sea-ice melting over the Canada Basin. AB - Arctic climate changes include not only changes in trends and mean states but also strong interannual variations in various fields. Although it is known that tropical-extratropical teleconnection is sensitive to changes in flavours of El Nino, whether Arctic climate variability is linked to El Nino, in particular on interannual timescale, remains unclear. Here we demonstrate for the first time a long-range linkage between central Pacific (CP) El Nino and summer Arctic climate. Observations show that the CP warming related to CP El Nino events deepens the tropospheric Arctic polar vortex and strengthens the circumpolar westerly wind, thereby contributing to inhibiting summer Arctic warming and sea ice melting. Atmospheric model experiments can generally capture the observed responses of Arctic circulation and robust surface cooling to CP El Nino forcing. We suggest that identification of the equator-Arctic teleconnection, via the 'atmospheric bridge', can potentially contribute to improving the skill of predicting Arctic climate. PMID- 27251874 TI - A highly efficient supramolecular photoswitch for singlet oxygen generation in water. AB - A series of water-soluble supramolecular assemblies were constructed from dithienylethene-modified permethyl-beta-cyclodextrins and porphyrin derivatives, accompanied by a high FRET efficiency, and could be applied in the control of singlet oxygen generation in a 1% ethanol aqueous solution upon irradiation of different wavelength light. These findings will provide a feasible and convenient way to construct a potential photodynamic therapy material. PMID- 27251875 TI - Effect of Continuous Positive Airway Pressure on Blood Pressure Variability in Patients With Obstructive Sleep Apnea. AB - Obstructive sleep apnea (OSA) is a common risk factor for cardiovascular disease. Continuous positive airway pressure (CPAP) improves OSA symptoms and blood pressure (BP) control. The effect of CPAP on BP variability (BPV) in patients with and without hypertension treated with autotitrating CPAP (APAP) for 2 weeks was studied. A total of 78 participants (76.9% men, 49% hypertensive, mean body mass index 36.2 [6.9] kg/m2 , age 49.0 [12.9] years) underwent 2 weeks of APAP therapy. Office BP, BPV (standard deviation of three BP measurements), and pulse rate were measured before and after treatment. Systolic BPV (5.3+/-4.9 vs 4.2+/ 3.4 mm Hg, P=.047) and pulse rate (78.0+/-14.5 vs 75.5+/-15.8 beats per minute, P=.032) decreased after treatment, particularly in hypertensive participants. Mask leak was independently associated with reduced changes in systolic BPV (r= 0.237, P=.048). Short-term APAP treatment reduced BPV and pulse rate, particularly in hypertensive patients with OSA. PMID- 27251876 TI - Soft-template construction of three-dimensionally ordered inverse opal structure from Li2FeSiO4/C composite nanofibers for high-rate lithium-ion batteries. AB - Exploring a new method to fabricate small-sized nanofibers is essential to achieve superior performances for energy conversion and storage devices. Here, a novel soft-template strategy is developed to synthesize a three-dimensionally ordered macroporous (3DOM) architecture constructed from small-sized nanofibers. The effectiveness of a nanofiber-assembled three-dimensional inverse opal material as an electrode for high-rate lithium-ion batteries is demonstrated. The small-sized Li2FeSiO4/C composite nanofibers with a diameter of 20-30 nm are grown by employing a tri-block copolymer P123 as a structure directing agent. Accordingly, the macro-mesoporous hierarchical 3DOM architecture constructed from Li2FeSiO4/C nanofibers is further templated from P123 for the nanofibers and a polystyrene colloidal crystal array for the 3DOM architecture. We find that the thermal stability of the nanofiber morphology depends on the self-limited growth of Li2FeSiO4 nanocrystals in a crystalline-amorphous hybrid. As a cathode for a lithium-ion battery, the 3D hierarchical macro-mesoporous cathodes exhibit outstanding high-rate and ultralong-life performances with a capacity retention of 84% after 1500 cycles at 5 C in the voltage window of 1.5-4.5 V, which is greatly improved compared with a simple 3DOM Li2FeSiO4/C nanocomposite. PMID- 27251877 TI - Annexin A5 is the Most Abundant Membrane-Associated Protein in Stereocilia but is Dispensable for Hair-Bundle Development and Function. AB - The phospholipid- and Ca(2+)-binding protein annexin A5 (ANXA5) is the most abundant membrane-associated protein of ~P23 mouse vestibular hair bundles, the inner ear's sensory organelle. Using quantitative mass spectrometry, we estimated that ANXA5 accounts for ~15,000 copies per stereocilium, or ~2% of the total protein there. Although seven other annexin genes are expressed in mouse utricles, mass spectrometry showed that none were present at levels near ANXA5 in bundles and none were upregulated in stereocilia of Anxa5(-/-) mice. Annexins have been proposed to mediate Ca(2+)-dependent repair of membrane lesions, which could be part of the repair mechanism in hair cells after noise damage. Nevertheless, mature Anxa5(-/-) mice not only have normal hearing and balance function, but following noise exposure, they are identical to wild-type mice in their temporary or permanent changes in hearing sensitivity. We suggest that despite the unusually high levels of ANXA5 in bundles, it does not play a role in the bundle's key function, mechanotransduction, at least until after two months of age in the cochlea and six months of age in the vestibular system. These results reinforce the lack of correlation between abundance of a protein in a specific compartment or cellular structure and its functional significance. PMID- 27251878 TI - Bilingual Text4Walking Food Service Employee Intervention Pilot Study. AB - BACKGROUND: Half of all adults in the United States do not meet the level of recommended aerobic physical activity. Physical activity interventions are now being conducted in the workplace. Accessible technology, in the form of widespread usage of cell phones and text messaging, is available for promoting physical activity. OBJECTIVE: The purposes of this study, which was conducted in the workplace, were to determine (1) the feasibility of implementing a bilingual 12-week Text4Walking intervention and (2) the effect of the Text4Walking intervention on change in physical activity and health status in a food service employee population. METHODS: Before conducting the study reported here, the Text4Walking research team developed a database of motivational physical activity text messages in English. Because Hispanic or Latino adults compose one-quarter of all adults employed in the food service industry, the Text4Walking team translated the physical activity text messages into Spanish. This pilot study was guided by the Physical Activity Health Promotion Framework and used a 1-group 12 week pre- and posttest design with food service employees who self-reported as being sedentary. The aim of the study was to increase the number of daily steps over the baseline by 3000 steps. Three physical activity text messages were delivered weekly. In addition, participants received 3 motivational calls during the study. RESULTS: SPSS version 19.0 and R 3.0 were used to perform the data analysis. There were 33 employees who participated in the study (57.6% female), with a mean age of 43.7 years (SD 8.4). The study included 11 Hispanic or Latino participants, 8 of whom requested that the study be delivered in Spanish. There was a 100% retention rate in the study. At baseline, the participants walked 102 (SD 138) minutes/day (per self-report). This rate increased significantly (P=.008) to 182 (SD 219) minutes/day over the course of the study. The participants had a baseline mean of 10,416 (SD 5097) steps, which also increased significantly (P=.017) to 12,540 (SD 5149). They significantly improved their performance on their aerobic fitness test (P<.001). The participants had a baseline mean systolic blood pressure of 120 mm Hg and diastolic blood pressure of 76 mm Hg, a mean body mass index of 29.29 kg/m2, and a mean waist circumference of 36.95 inches, without significant changes seen at 12 weeks. CONCLUSIONS: We were able to conduct a motivational physical activity text messaging intervention within the workplace setting. Both physical activity and aerobic fitness improved. However, at baseline, participants were more active than they perceived themselves to be. Although there is insufficient evidence to draw strong conclusions about the study findings, it would be useful to test this physical activity text messaging intervention in a sedentary sample within a larger workplace intervention study trial conducted over a longer time frame. PMID- 27251879 TI - Sodium Ion Transport Mechanisms in Antiperovskite Electrolytes Na3OBr and Na4OI2: An in Situ Neutron Diffraction Study. AB - Na-rich antiperovskites are recently developed solid electrolytes with enhanced sodium ionic conductivity and show promising functionality as a novel solid electrolyte in an all solid-state battery. In this work, the sodium ionic transport pathways of the parent compound Na3OBr, as well as the modified layered antiperovskite Na4OI2, were studied and compared through temperature-dependent neutron diffraction combined with the maximum entropy method. In the cubic Na3OBr antiperovskite, the nuclear density distribution maps at 500 K indicate that sodium ions hop within and among oxygen octahedra, and Br(-) ions are not involved. In the tetragonal Na4OI2 antiperovskite, Na ions, which connect octahedra in the ab plane, have the lowest activation energy barrier. The transport of sodium ions along the c axis is assisted by I(-) ions. PMID- 27251880 TI - Application of vancomycin in patients with varying renal function, especially those with augmented renal clearance. AB - CONTEXT: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute, and has attracted wide attention in recent years. OBJECTIVE: This study evaluates the effects of ARC on serum vancomycin concentration in patients administered vancomycin. MATERIALS AND METHODS: This was a retrospective study in patients receiving vancomycin treatment at a dose of 1000 mg in every 12 h and undergoing serum monitoring admitted over a 2-year period (May 2013 to May 2015), in order to estimate the influence of ARC on serum vancomycin concentration. In this study, statistical comparisons were made on the results from patients grouped according to creatinine clearance (CLcr). RESULTS: One hundred forty-eight patients were enrolled in our study. The results showed that ARC patients were significantly younger, with a significantly lower Scr and higher GFR. The CLcr and steady-state trough concentrations of serum vancomycin exhibited a logarithmic correlation (Rs = -0.699, R2 = 0.488, p < 0.01) in the patients included in our study. The trough vancomycin concentrations of 62.9% patients in high CLcr group were under 10 MUg/mL. DISCUSSION AND CONCLUSION: Since ARC was significantly associated with subtherapeutic serum vancomycin concentration, it was necessary to devise adjusted dosage regimens for these patients based on their CLcr. PMID- 27251882 TI - Comment: A quick and reliable test of peripheral vestibular function-On an impulse. PMID- 27251881 TI - Linker design for the modular assembly of multifunctional and targeted platinum(ii)-containing anticancer agents. AB - A versatile and efficient modular synthetic platform was developed for assembling multifunctional conjugates and targeted forms of platinum-(benz)acridines, a class of highly cytotoxic DNA-targeted hybrid agents. The synthetic strategy involved amide coupling between succinyl ester-modified platinum compounds (P1, P2) and a set of 11 biologically relevant primary and secondary amines (N1-N11). To demonstrate the feasibility and versatility of the approach, a structurally and functionally diverse range of amines was introduced. These include biologically active molecules, such as rucaparib (a PARP inhibitor), E/Z endoxifen (an estrogen receptor antagonist), and a quinazoline-based tyrosine kinase inhibitor. Micro-scale reactions in Eppendorf tubes or on 96-well plates were used to screen for optimal coupling conditions in DMF solution with carbodiimide-, uronium-, and phosphonium-based compounds, as well as other common coupling reagents. Reactions with the phosphonium-based coupling reagent PyBOP produced the highest yields and gave the cleanest conversions. Furthermore, it was demonstrated that the chemistry can also be performed in aqueous media and is amenable to parallel synthesis based on multiple consecutive reactions in DMF in a "one-tube" format. In-line LC-MS was used to assess the stability of the conjugates in physiologically relevant buffers. Hydrolysis of the conjugates occurs at the ester moiety and is facilitated by the aquated metal moiety under low-chloride ion conditions. The rate of ester cleavage greatly depends on the nature of the amine component. Potential applications of the linker technology are discussed. PMID- 27251883 TI - Temozolomide induces radiologic pseudoprogression and tumor cell vanishing in oligodendroglioma. PMID- 27251884 TI - A new saccadic indicator of peripheral vestibular function based on the video head impulse test. AB - OBJECTIVE: While compensatory saccades indicate vestibular loss in the conventional head impulse test paradigm (HIMP), in which the participant fixates an earth-fixed target, we investigated a complementary suppression head impulse paradigm (SHIMP), in which the participant is fixating a head-fixed target to elicit anticompensatory saccades as a sign of vestibular function. METHODS: HIMP and SHIMP eye movement responses were measured with the horizontal video head impulse test in patients with unilateral vestibular loss, patients with bilateral vestibular loss, and in healthy controls. RESULTS: Vestibulo-ocular reflex gains showed close correlation (R(2) = 0.97) with slightly lower SHIMP than HIMP gains (mean gain difference 0.06 +/- 0.05 SD, p < 0.001). However, the 2 paradigms produced complementary catch-up saccade patterns: HIMP elicited compensatory saccades in patients but rarely in controls, whereas SHIMP elicited large anticompensatory saccades in controls, but smaller or no saccades in bilateral vestibular loss. Unilateral vestibular loss produced covert saccades in HIMP, but later and smaller saccades in SHIMP toward the affected side. Cumulative HIMP and SHIMP saccade amplitude differentiated patients from controls with high sensitivity and specificity. CONCLUSIONS: While compensatory saccades indicate vestibular loss in conventional HIMP, anticompensatory saccades in SHIMP using a head-fixed target indicate vestibular function. SHIMP saccades usually appear later than HIMP saccades, therefore being more salient to the naked eye and facilitating vestibulo-ocular reflex gain measurements. The new paradigm is intuitive and easy to explain to patients, and the SHIMP results complement those from the standard video head impulse test. CLASSIFICATION OF EVIDENCE: This case control study provides Class III evidence that SHIMP accurately identifies patients with unilateral or bilateral vestibulopathies. PMID- 27251885 TI - Sex hormones in women with and without migraine: Evidence of migraine-specific hormone profiles. AB - OBJECTIVE: To compare daily sex hormone levels and rates of change between women with history of migraine and controls. METHODS: History of migraine, daily headache diaries, and daily hormone data were collected in ovulatory cycles of pre- and early perimenopausal women in the Study of Women's Health Across the Nation. Peak hormone levels, average daily levels, and within-woman day-to-day rates of decline over the 5 days following each hormone peak were calculated in ovulatory cycles for conjugated urinary estrogens (E1c), pregnanediol-3 glucuronide, luteinizing hormone, and follicle-stimulating hormone. Comparisons were made between migraineurs and controls using 2-sample t tests on the log scale with results reported as geometric means. RESULTS: The sample included 114 women with history of migraine and 223 controls. Analyses of within-woman rates of decline showed that E1c decline over the 2 days following the luteal peak was greater in migraineurs for both absolute rate of decline (33.8 [95% confidence interval 28.0-40.8] pg/mgCr vs 23.1 [95% confidence interval 20.1-26.6] pg/mgCr, p = 0.002) and percent change (40% vs 30%, p < 0.001). There was no significant difference between migraineurs and controls in absolute peak or daily E1c, pregnanediol-3-glucuronide, luteinizing hormone, and follicle-stimulating hormone levels. Secondary analyses demonstrated that, among migraineurs, the rate of E1c decline did not differ according to whether a headache occurred during the cycle studied. CONCLUSIONS: Migraineurs are characterized by faster late luteal phase E1c decline compared to controls. The timing and rate of estrogen withdrawal before menses may be a marker of neuroendocrine vulnerability in women with migraine. PMID- 27251888 TI - Comment on 'Novel anticoagulants - an update on the latest developments and management for clinicians treating patients on these drugs'. PMID- 27251886 TI - Carbon isotope fractionation reveals distinct process of CH4 emission from different compartments of paddy ecosystem. AB - Carbon isotopic fractionations in the processes of CH4 emission from paddy field remain poorly understood. The delta(13)C-values of CH4 in association with production, oxidation and transport of CH4 in different pools of a paddy field were determined, and the stable carbon isotope fractionations were calibrated to assess relative contribution of acetate to CH4 production (fac) and fraction of CH4 oxidized (fox) by different pathways. The apparent isotope fractionation for CO2 conversion to CH4 (alphaapp) was 1.041-1.056 in the soil and 1.046-1.080 on the roots, indicating that fac was 10-60% and 0-50%, respectively. Isotope fractionation associated with CH4 oxidation (alphaox) was 1.021 +/- 0.007 in the soil and 1.013 +/- 0.005 on the roots, and the transport fractionation (epsilontransport) by rice plants was estimated to be -16.70/00 ~ -11.10/00. Rhizospheric fox was about 30-100%, and it was more important at the beginning but decreased fast towards the end of season. Large value of fox was also observed at the soil-water interface and soil and roots surfaces, respectively. The results demonstrate that carbon isotopic fractionations which might be different in different conditions were sensitive to the estimations of fac and fox in paddy field. PMID- 27251889 TI - In vivo Magnetic Resonance Microscopy and Hypothermic Anaesthesia of a Disease Model in Medaka. AB - In medical and pharmacological research, various human disease models in small fish, such as medaka (Oryzias latipes), have been created. To investigate these disease models noninvasively, magnetic resonance imaging (MRI) is suitable because these small fish are no longer transparent as adults. However, their small body size requires a high spatial resolution, and a water pool should be avoided to maximize the strength of MRI. We developed in vivo magnetic resonance microscopy (MR microscopy) without a water pool by combining hypothermic anaesthesia and a 14.1 T MR microscope. Using in vivo MR microscopy, we noninvasively evaluated the hepatic steatosis level of a non-alcoholic fatty liver disease model in medaka and followed the individual disease progression. The steatosis level was quantified by the MRI-estimated proton density fat fraction (MRI-PDFF), which estimates the triglyceride fat concentration in liver tissue and is recognized as an imaging biomarker. The MRI-PDFF results agreed with a histological analysis. Moreover, we optimized the hypothermic anaesthesia procedure to obtain a recovery proportion of 1 in the experiment involving MR microscopy. Recovered medaka could not be distinguished from naive medaka after the experiment. Therefore, the in vivo MR microscopy will expand the possibilities of a human disease model in fish. PMID- 27251890 TI - "Sorry, I'm Not Accepting New Patients": An Audit Study of Access to Mental Health Care. AB - Through a phone-based field experiment, I investigated the effect of mental help seekers' race, class, and gender on the accessibility of psychotherapists. Three hundred and twenty psychotherapists each received voicemail messages from one black middle-class and one white middle-class help seeker, or from one black working-class and one white working-class help seeker, requesting an appointment. The results revealed an otherwise invisible form of discrimination. Middle-class help seekers had appointment offer rates almost three times higher than their working-class counterparts. Race differences emerged only among middle-class help seekers, with blacks considerably less likely than whites to be offered an appointment. Average appointment offer rates were equivalent across gender, but women were favored over men for appointment offers in their preferred time range. PMID- 27251891 TI - Challenges Evaluating Chemotherapy-Induced Peripheral Neuropathy in Childhood Cancer Survivors. AB - Children treated for cancer are exposed to a variety of chemotherapeutic agents with known toxicity to the peripheral nervous system. The side effect of peripheral neuropathy can cause changes in sensation, function, and even cause pain. Although peripheral neuropathy is recognized by pediatric oncology nurses as an important and significant side effect, measuring neuropathy can be quite complex for clinical care and research efforts. With more children surviving a cancer diagnosis today, this issue is increasingly important for childhood cancer survivors. This article has reviewed existing literature examining peripheral neuropathy in childhood cancer survivors with particular interest paid to measurement tools available and needs for future research. It is important for nurses to choose appropriate measures for clinical care and research methods in order to have an impact on patients experiencing this condition. PMID- 27251892 TI - Optimal processing for gel electrophoresis images: Applying Monte Carlo Tree Search in GelApp. AB - In biomedical research, gel band size estimation in electrophoresis analysis is a routine process. To facilitate and automate this process, numerous software have been released, notably the GelApp mobile app. However, the band detection accuracy is limited due to a band detection algorithm that cannot adapt to the variations in input images. To address this, we used the Monte Carlo Tree Search with Upper Confidence Bound (MCTS-UCB) method to efficiently search for optimal image processing pipelines for the band detection task, thereby improving the segmentation algorithm. Incorporating this into GelApp, we report a significant enhancement of gel band detection accuracy by 55.9 +/- 2.0% for protein polyacrylamide gels, and 35.9 +/- 2.5% for DNA SYBR green agarose gels. This implementation is a proof-of-concept in demonstrating MCTS-UCB as a strategy to optimize general image segmentation. The improved version of GelApp-GelApp 2.0-is freely available on both Google Play Store (for Android platform), and Apple App Store (for iOS platform). PMID- 27251893 TI - Tetradentate polyamines as efficient metallodrugs for Chagas disease treatment in murine model. AB - A series of tetraamine-based compounds was prepared, and their trypanocidal effects against Trypanosoma cruzi and cytotoxicity were determined through the determination of IC50 values. In vivo assays were performed in mice, where parasitaemia levels were quantified by fresh blood examination and the assignment of a cure was determined by polymerase chain reaction and reactivation of blood parasitaemia levels after immunosuppression. The mechanisms of action were elucidated at metabolic and ultra-structural levels, by 1H NMR, Fe-SOD inhibition and TEM studies. The high-selectivity indexes observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. Compound 6 induced a remarkable decrease in the reactivation of parasitaemia after immunosuppression and curative rates of 33%. The experiments allowed us to select compound 6 as a promising candidate for treating Chagas disease, but a further high-level study should be considered to obtain an improved efficiency. PMID- 27251895 TI - If overuse injury is a 'training load error', should undertraining be viewed the same way? PMID- 27251896 TI - Current state of concussion prevention strategies: a systematic review and meta analysis of prospective, controlled studies. AB - OBJECTIVE: The aim of the current review was to systematically identify, evaluate and synthesise trials that examine concussion prevention via equipment, educational programmes and training programmes. DATA SOURCES: PubMed and EBSCO host (CINAHL, MEDLINE, SPORTDiscus). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: The electronic databases PubMed and EBSCO were searched using the phrases: concussion prevention equipment, concussion prevention training and concussion prevention education. Included studies utilised a prospective study design to evaluate the preventative effect of: (1) equipment, (2) training or (3) educational programmes on the incidence of concussions in comparison to a control group. DATA EXTRACTION: Demographic data and intervention methods were recorded. Intervention and control group concussion rates and superficial head injury rates were extracted and combined using random-effects relative risk meta-analysis. RESULTS: 14 studies evaluated interventions of novel protective equipment. One prospective investigation evaluated an educational programme. The relative risk of concussion for participants enrolled in the interventional arms of trials was not significantly different from that in standard practice arms (RR=0.78, 95% CI 0.55 to 1.11, chi2=1.8, p=0.17; I2=85.3%, 95% CI 71.5% to 90.8%). The relative risk of concussion for participants wearing protective equipment (ie, headgear, full face shields) relative to their counterparts wearing standard or no equipment, calculated from seven available reports, showed no effect of intervention (RR=0.82, 95% CI 0.56 to 1.20, chi2=1.06, p=0.30; I2=86.7%, 95% CI 73.3% to 91.8%). The relative risk of superficial head injury for participants wearing protective equipment relative to their counterparts, calculated from three reports, showed a significant risk reduction (RR=0.41, 95% CI 0.31 to 0.56, chi2=34.13, p<0.0001; I2=53.1%, 95% CI 0% to 85.2%). CONCLUSIONS: Prospective controlled studies indicate that certain protective equipment may prevent superficial head injury, but these items are suboptimal for concussion prevention in sport. PMID- 27251897 TI - Clinical outcomes of a scapular-focused treatment in patients with subacromial pain syndrome: a systematic review. AB - OBJECTIVE: To systematically review the literature on the clinical outcomes of scapular-focused treatments in participants with subacromial pain syndrome (SPS). DESIGN: Systematic literature review. Studies were appraised by two reviewers using the Physiotherapy Evidence Database (PEDro) scale, and a best-evidence synthesis was performed. DATA SOURCES: The literature search was conducted in the databases PubMed, Embase and Cinahl up to February 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials evaluating the clinical outcomes of a physiotherapeutic scapular-focused treatment in participants with SPS. RESULTS: Four studies were included describing various scapular-focused interventions, including scapular-focused exercise therapy, scapular mobilisation and scapular taping. All included studies had a PEDro score of 6 or higher, indicating low risk of bias. There was moderate evidence that scapular-focused treatment compared with other physiotherapeutic treatment is effective in improving scapular muscle strength in participants with SPS. Conflicting evidence was found for improvements in pain, function and clinical measures of scapular positioning. No evidence was found for improvements in shoulder range of motion or rotator cuff muscle strength. CONCLUSIONS: There is some support for the use of scapular-focused exercise therapy in patients with SPS. Owing to the low number of studies, no firm conclusions can be drawn. Therefore, more randomised controlled trials are needed to determine the clinical outcomes of scapular focused exercise therapy, scapular mobilisation techniques and scapular taping in patients with SPS. PMID- 27251898 TI - Critical components of neuromuscular training to reduce ACL injury risk in female athletes: meta-regression analysis. AB - OBJECTIVE: The aim of this study was to determine key components in neuromuscular training that optimise ACL injury reduction in female athletes using meta regression analyses. DESIGN: Systematic review and meta-regression. DATA SOURCES: The literature search was performed in PubMed and EBSCO. ELIGIBILITY CRITERIA: Inclusion criteria for the current analysis were: (1) documented the number of ACL injuries, (2) employed a neuromuscular training intervention that aimed to reduce ACL injuries, (3) had a comparison group, (4) used a prospective control study design and (5) recruited female athletes as participants. Two independent reviewers extracted studies which met the inclusion criteria. Methodological quality of included study and strength of recommendation were evaluated. Number of ACL injuries and participants in control and intervention groups, age of participants, dosage of neuromuscular training, exercise variations within neuromuscular training and status of verbal feedback were extracted. RESULTS: The meta-regression analyses identified age of participants, dosage of neuromuscular training, exercise variations within neuromuscular training and utilisation of verbal feedback as significant predictors of ACL injury reduction (p=0.01 in fixed-effects model, p=0.03 in random-effects model). Inclusion of 1 of the 4 components in neuromuscular training could reduce ACL injury risk by 17.2-17.7% in female athletes. No significant heterogeneity and publication bias effects were detected. Strength of recommendation was rated as A (recommendation based on consistent and good-quality patient-oriented study evidence). CONCLUSIONS: Age of participants, dosage of neuromuscular training, exercise variations within neuromuscular training and utilisation of verbal feedback are predictors that influence the optimisation of prophylactic effects of neuromuscular training and the resultant ACL injury reduction in female athletes. PMID- 27251899 TI - Longevity protein klotho is induced by a single bout of exercise. PMID- 27251900 TI - Centrofacial Balamuthiasis: case report of a rare cutaneous amebic infection. AB - Free-living amebae are ubiquitous in our environment, but rarely cause cutaneous infection. Balamuthia mandrillaris has a predilection for infecting skin of the central face. Infection may be restricted to the skin or associated with life threatening central nervous system (CNS) involvement. We report a case of a 91 year-old woman, who presented with a non-healing red plaque over her right cheek. Several punch biopsies exhibited non-specific granulomatous inflammation without demonstrable fungi or mycobacteria in histochemical stains. She was treated empirically for granulomatous rosacea, but the lesion continued to progress. A larger incisional biopsy was performed in which amebae were observed in hematoxylin-eosin stained sections. These were retrospectively apparent in the prior punch biopsy specimens. Immunohistochemistry and polymerase chain reaction studies identified the organisms as Balamuthia mandrillaris. Cutaneous infection by B. mandrillaris is a rare condition that is sometimes complicated by life threatening CNS involvement and which often evades timely diagnosis due to its rarity and nonspecific clinical manifestations. Moreover, these amebae are easily overlooked in histopathologic sections because of their small number and their resemblance to histiocytes. Dermatopathologists should be familiar with the histopathologic appearance of these organisms and include balamuthiasis and other amebic infections in the differential diagnosis of granulomatous dermatitis. PMID- 27251901 TI - Quantification of common carotid artery and descending aorta vessel wall thickness from MR vessel wall imaging using a fully automated processing pipeline. AB - PURPOSE: To develop and evaluate a method that can fully automatically identify the vessel wall boundaries and quantify the wall thickness for both common carotid artery (CCA) and descending aorta (DAO) from axial magnetic resonance (MR) images. MATERIALS AND METHODS: 3T MRI data acquired with T1 -weighted gradient-echo black-blood imaging sequence from carotid (39 subjects) and aorta (39 subjects) were used to develop and test the algorithm. The vessel wall segmentation was achieved by respectively fitting a 3D cylindrical B-spline surface to the boundaries of lumen and outer wall. The tube-fitting was based on the edge detection performed on the signal intensity (SI) profile along the surface normal. To achieve a fully automated process, Hough Transform (HT) was developed to estimate the lumen centerline and radii for the target vessel. Using the outputs of HT, a tube model for lumen segmentation was initialized and deformed to fit the image data. Finally, lumen segmentation was dilated to initiate the adaptation procedure of outer wall tube. The algorithm was validated by determining: 1) its performance against manual tracing; 2) its interscan reproducibility in quantifying vessel wall thickness (VWT); 3) its capability of detecting VWT difference in hypertensive patients compared with healthy controls. Statistical analysis including Bland-Altman analysis, t-test, and sample size calculation were performed for the purpose of algorithm evaluation. RESULTS: The mean distance between the manual and automatically detected lumen/outer wall contours was 0.00 +/- 0.23/0.09 +/- 0.21 mm for CCA and 0.12 +/- 0.24/0.14 +/- 0.35 mm for DAO. No significant difference was observed between the interscan VWT assessment using automated segmentation for both CCA (P = 0.19) and DAO (P = 0.94). Both manual and automated segmentation detected significantly higher carotid (P = 0.016 and P = 0.005) and aortic (P < 0.001 and P = 0.021) wall thickness in the hypertensive patients. CONCLUSION: A reliable and reproducible pipeline for fully automatic vessel wall quantification was developed and validated on healthy volunteers as well as patients with increased vessel wall thickness. This method holds promise for helping in efficient image interpretation for large-scale cohort studies. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:215-228. PMID- 27251902 TI - Early pathology in sleep studies of patients with familial Creutzfeldt-Jakob disease. AB - In this study, we aimed to assess sleep function in patients with recent-onset familial Creutzfeldt-Jakob disease (fCJD). The largest cluster of fCJD patients is found in Jews of Libyan origin, linked to the prion protein gene (PRNP) E200K mutation. The high index of suspicion in these patients often leads to early diagnosis, with complaints of insomnia being a very common presenting symptom of the disease. The study included 10 fCJD patients diagnosed by clinical manifestations, magnetic resonance imaging (MRI) scan of the brain, elevated tau protein in the cerebrospinal fluid (CSF) and positive PRNP E200K mutation. Standard polysomnography was performed after a brief interview confirming the presence of sleep disturbances. All patients showed a pathological sleep pattern according to all scoring evaluation settings. The sleep stages were characterized by (i) disappearance of sleep spindles; (ii) outbursts of periodic sharp waves and shallowing of sleep consisting in increased Stage 2 and wake periods during the night, as well as decrease of slow-wave sleep and rapid eye movement (REM) sleep. Recordings of respiratory functions reported irregular breathing with central and obstructive apnea and hypopnea. The typical hypotonia occurring during the night and atonia during REM sleep were replaced by hyperactive sleep consisting of multiple jerks, movements and parasomnia (mainly talking) throughout the night. In conclusion, we report unique pathological sleep patterns in early fCJD associated with the E200K mutation. Specific respiratory disturbances and lack of atonia could possibly serve as new, early diagnostic tools in the disease. PMID- 27251903 TI - Clinical toxicity following analytically confirmed use of the synthetic cannabinoid receptor agonist MDMB-CHMICA. A report from the Identification Of Novel psychoActive substances (IONA) study. AB - CONTEXT: Recreational use of Synthetic Cannabinoid Receptors Agonists (SCRAs) has become increasingly common in many countries and may cause severe toxic effects. OBJECTIVE: To describe the clinical features of toxicity in seven men after analytically confirmed exposure to MDMB-CHMICA, a recently described indole-based SCRA. MATERIALS AND METHODS: Clinical information and biological samples (blood, urine) were collected from patients with severe toxicity after suspected use of novel psychoactive substances. Samples were analyzed by data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE REPORTS: All seven cases were men who presented to hospitals in England between July and October 2015; six reported smoking "legal high" products. In all cases, MDMB-CHMICA was identified in blood samples taken on admission to hospital. Other substances were identified in four cases (methadone 1, methiopropamine 1, other SCRAs 2). Clinical features in all seven cases and in the three exposed to MDMB-CHIMICA alone included acidosis (7/7 and 3/3) which was respiratory (3/7 and 3/3), metabolic (3/7 and 0/3) or mixed (1/7, 0/3), reduced level of consciousness (6/7 and 3/3), mydriasis (5/7 and 3/3), tachycardia (5/7 and 2/3), bradycardia (2/7 and 1/3), tonic-clonic convulsions (2/7 and 1/3) and agitation (3/7 and 1/3). Recovery occurred within 24 h in all cases except one male also exposed to methiopropamine. CONCLUSIONS: Analytically confirmed exposure to MDMB-CHMICA was associated with acidosis (often of respiratory origin), reduced level of consciousness, mydriasis, heart rate disturbances and convulsions. PMID- 27251904 TI - Clinical leishmaniasis in dogs living in the UK. AB - OBJECTIVES: To investigate the prevalence of leishmaniasis in dogs in the UK and to describe clinical presentation, clinicopathological abnormalities, therapeutic protocols and outcome in this non-endemic country. MATERIALS AND METHODS: Medical records of dogs diagnosed with leishmaniasis at seven referral centres in the UK were retrospectively reviewed. RESULTS: The prevalence was between 0.007 and 0.04% with a higher number of cases in southern England. All dogs had a history of travel to or from an endemic country. Lethargy, dermatological disease, decreased appetite and lameness were the most common reasons for presentation. Allopurinol was used alone for treatment in the majority of cases. CLINICAL SIGNIFICANCE: Although rare, leishmaniasis should be considered in dogs in the UK if they have compatible clinical signs and history of travel to or from endemic areas. PMID- 27251906 TI - Clinician scientists in training. PMID- 27251907 TI - Ambitions for palliative and end-of-life care. PMID- 27251905 TI - Insights into autophagosome biogenesis from in vitro reconstitutions. AB - Macro-autophagy (autophagy) is a conserved catabolic pathway for the degradation of cytoplasmic material in the lysosomal system. This is achieved by the sequestration of the cytoplasmic cargo material within double membrane-bound vesicles that fuse with lysosomes, wherein the vesicle's inner membrane and the cargo are degraded. Autophagosomes form in a de novo manner and their precursors are initially detected as small membrane structures that are referred to as isolation membranes. The isolation membranes gradually expand and subsequently close to give rise to autophagosomes. Many proteins required to form autophagosomes have been identified but how they act mechanistically is still enigmatic. Here we critically review reconstitution approaches employed to decipher the inner working of the fascinating autophagy machinery. PMID- 27251908 TI - The combined medical/PhD degree: a global survey of physician-scientist training programmes. AB - Typically lasting 7-9 years, medical-scientist training programmes (MSTPs) allow students a unique opportunity to simultaneously intercalate medical (MBBS, MBChB or MD) and research (PhD) degrees. The nature of both degrees means that the combined programme is arduous, and selection is often restricted to a few highly motivated students. Despite the many successes of MSTPs, enthusiasm about MSTPs and the number of intercalating students, at least in some countries, appear to be diminishing. In this review, I shed light on MSTPs around the world, highlight the plethora of successes such programmes have had and provide insights on the setbacks experienced and solutions offered, with the aim of reigniting interest in these programmes. PMID- 27251909 TI - Blurred lines: the General Medical Council guidance on doctors and social media . AB - Digital technology in the early 21st century has introduced significant changes to everyday life and the ways in which we practise medicine. It is important that the ease and practicality of accessing and disseminating information does not intrude on the high standards expected of doctors, and that the boundaries between professional and public life do not become blurred through the increasing adoption of social media. This said, as with any such profound disruption, the social media age could be responsible for driving a new understanding of what it means to be a medical professional. PMID- 27251910 TI - Randomised controlled trial of GP-led in-hospital management of homeless people ('Pathway'). AB - Homeless people have complex problems. GP enhanced care (Pathway) has shown benefits. We performed a randomised, -parallel arm trial at two large inner city hospitals. Inpatient homeless adults were randomly allocated to either standard care (all management by the hospital-based clinical team) or enhanced care with input from a homeless care team. The hospital data system provided healthcare usage information, and we used questionnaires to assess quality of life. 206 patients were allocated to enhanced care and 204 to usual care. Length of stay (up to 90 days after admission) did not differ between groups (standard care 14.0 days, enhanced care 13.3 days). Average reattendance at the emergency department within a year was 5.8 visits in the standard care group and 4.8 visits with enhanced care, but this decrease was not significant. -Quality of life scores after discharge (in 108 patients) improved with enhanced care (EQ-5D-5L score increased by 0.12 [95% CI 0.032 to 0.22] compared wtih 0.03 [-0.1 to 0.15; p=0.076] with standard care). The proportion of people sleeping on the streets after discharge was 14.6% in the standard care arm and 3.8% in the enhanced care arm (p=0.034). The quality-of-life cost per quality-adjusted life-year was L26,000. The Pathway approach doesn't alter length of stay but improves quality of life and reduces street -homelessness. PMID- 27251911 TI - An in vitro analysis of the effect of acidosis on coagulation in chronic disease states - a thromboelastograph study. AB - Thrombosis is a complication of many chronic illnesses. Chronic obstructive pulmonary disease (COPD) and diabetes mellitus are common medical conditions frequently associated with a hypercoagulable state. Acidaemia has been shown to reduce coagulation. COPD and diabetes mellitus during acute deterioration can present with a severe acidaemia. The impact of this acidaemia on coagulation is poorly studied. Patients presenting with a diagnosis of diabetic ketoacidosis or type II respiratory failure from COPD and a pH of less than 7.2 were included in our study. A coagulation screen and a thromboelastograph (TEG) were performed on admission and 24 hours later. The mean pH on admission was 7.07 and mean base excess was -16.3. The activated partial thromboplastin time was associated with pH change but remained within the normal range (26-41 s). All other coagulation and TEG parameters failed to show evidence of association (p>0.05). In the two models of non-haemorrhagic acidosis investigated, coagulation was not altered by the changes in pH. More work is needed to understand the complex relationship between factors affecting coagulation in individual disease processes. PMID- 27251912 TI - Service contribution and cost-effectiveness of specialist registrars in NHS trusts: a survey and costing analysis. AB - Since the introduction of the European Working Time Directive, specialist registrars arguably contribute less to clinical service. The purpose of this study was to broadly quantify the service contribution of specialist registrars across a range of specialties and their value to an NHS organisation. A questionnaire-based survey of the clinical activities of specialist registrars in a large NHS trust was undertaken. Simple costing analyses of this -clinical activity were performed. Responses from 66 specialist registrars in 24 specialties showed an average of 51% overall clinical autonomy. Trainees attended an average of 2.7 outpatient clinics per week and spent 3.5 sessions a week doing ward work. Medical trainees took more referrals and attended more clinics. An analysis of costings suggested that surgical trainees might have generated around L700,000 income per year for the trust. Overall, specialist registrars make a substantial contribution to NHS clinical service and are cost-effective. PMID- 27251913 TI - The holistic management of consequences of cancer treatment by a gastrointestinal and nutrition team: a financially viable approach to an enormous problem? AB - There is no national NHS tariff to fund services for patients experiencing long term bowel and nutritional problems after cancer treatment. In this paper, we report the clinical characteristics and outcomes of patients referred to our service and the estimated cost of a completed episode of care. Patient characteristics, symptom severity, investigations, diagnoses, number of clinic visits and referrals elsewhere were recorded in a prospective cohort study. During 2013-14, 325 patients completed assessment and treatment. The majority of original cancer diagnoses were urological (43%) and gynaecological (21%). A median of six investigations were requested. 62% were found to have three or more new diagnoses including small intestinal bacterial overgrowth (46%), vitamin D deficiency (38%), bile acid malabsorption (28%), gastritis (22%), radiation induced bleeding (20%), vitamin B12 deficiency (17%), pelvic floor weakness (17%), colorectal polyps (13%) and pancreatic insufficiency (5%). A median of three visits were required and all commonly reported gastrointestinal symptoms improved by discharge. The mean episode of care per patient was costed at L1,563. Effective amelioration of chronic gastrointestinal toxicity after cancer treatment costs substantially less than treating the cancer in the first place and requires an NHS tariff. PMID- 27251914 TI - Drug treatments in Alzheimer's disease. AB - Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms rather than alter the course of the disease. Studies of potential disease-modifying therapy have generally been undertaken in patients with clinically detectable disease, yet evidence suggests that the pathological changes associated with AD begin several years before this. It is possible that pharmacological therapy may be beneficial in this pre-clinical stage before the neurodegenerative process is established. Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials. Recent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence. However, we currently remain a good distance away from clinically available disease-modifying therapy. PMID- 27251915 TI - Care of dying adults in the last days of life . AB - Care of people in their last days of life should be based on compassion, respect and, wherever possible, on research evidence. Previously the Liverpool Care Pathway attempted to facilitate this but it was withdrawn after an independent government report found that its uncritical implementation could lead to poor care. This Concise Guideline overviews NICE Clinical Guideline (NG31), which addresses: recognising dying; communication and shared decision making; maintaining hydration; and pharmacological symptom control, including anticipatory prescribing. Doctors may need to change their attitudes to care of dying people and those important to them. Specific areas where practices will need to reflect the individualised approach to care are highlighted. Limitations of the guideline are discussed. Potential barriers to implementation include need for further training and 24/7 availability of specialist support to front-line clinicians. PMID- 27251916 TI - Neuromuscular conditions for physicians - what you need to know. AB - The Royal College of Physicians (RCP) and the British Society of Rehabilitation Medicine co-hosted a meeting entitled 'Neuromuscular conditions for physicians - what you need to know' at the RCP on 30 November 2015. There was a series of talks, ranging from in-depth genetic and molecular descriptions of pathology to multidisciplinary management of chronic neuromuscular conditions, which stimulated lively debate and discussion. Some overarching themes emerged from the day, most notably: i) the changing expectations and survival rates in Duchenne muscular dystrophy (DMD), which are transforming this disorder into an adult as much as a paediatric condition; ii) the need for integrated management and good communication -between services - whether primary, secondary and tertiary care, medical teams and intensivists, or the multiple teams involved in providing treatment to neuromuscular patients; and iii) in line with the above, the essential need for streamlining care such that patients can avoid spending most of their time attending outpatient appointments, and instead concentrate on living full lives and exploring educational, occupational, leisure and social opportunities. PMID- 27251917 TI - Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance. AB - Polycystic ovary syndrome (PCOS) is a common condition that typically develops in reproductive-age women. The cardinal clinical and biochemical characteristics of PCOS include reproductive dysfunction and hyperandrogenic features. PCOS is also strongly associated with obesity based on data from epidemiological and genetic studies. Accordingly, PCOS often becomes manifest in those women who carry a genetic predisposition to its development, and who also gain weight. The role of weight gain and obesity in the development of PCOS is mediated at least in part, through worsening of insulin resistance. Compensatory hyperinsulinaemia that develops in this context disrupts ovarian function, with enhanced androgen production and arrest of ovarian follicular development. Insulin resistance also contributes to the strong association of PCOS with adverse metabolic risk, including dysglycaemia, dyslipidaemia and fatty liver. Conversely, modest weight loss of just 5% body weight with improvement in insulin sensitivity, frequently results in clinically meaningful improvements in hyperandrogenic, reproductive and metabolic features. Future developments of novel therapies for obese women with PCOS should focus on promotion of weight loss and improvement in insulin sensitivity. In this context, therapies that complement lifestyle changes such as dietary modification and exercise, particularly during the maintenance phase of weight loss are important. Putative novel targets for therapy in PCOS include human brown adipose tissue. PMID- 27251918 TI - The role of catheter ablation in the management of atrial fibrillation. AB - Atrial fibrillation is driven by spontaneous electrical activation emerging from the pulmonary veins. Catheter ablation using either radiofrequency or cryothermal energy electrically isolates these veins from the left atrium, both reducing the burden of atrial fibrillation episodes and improving the patient's symptoms. Catheter ablation is superior to antiarryhthmic drugs when patients are carefully selected. Underlying medical problems - including obesity, hypertension and obstructive sleep apnoea - should be optimally treated before considering ablation. Although this treatment has the potential to cure patients of their symptoms, they should be aware of the important associated procedural complications. PMID- 27251919 TI - The importance of interactions between atrial fibrillation and heart failure. AB - Heart failure (HF) and atrial fibrillation (AF) are among the commonest cardiovascular conditions encountered in clinical practice and frequently coexist. Over the last decade, they have evolved into global cardiovascular epidemics. This, in turn, has huge clinical and economic implications. There is ample evidence that AF and HF have a mutually deleterious effect on each other. AF is not only a marker of HF severity but also affects HF prognosis independently. This article presents the close pathophysiological relationship between AF and HF and the adverse prognostic consequences of this bidirectional interaction. The scope of various therapeutic modalities and their potential impacts are discussed briefly. PMID- 27251920 TI - ST elevation myocardial infarction. AB - ST segment elevation myocardial infarction remains a significant contributor to morbidity and mortality worldwide, despite a declining incidence and better survival rates. It usually results from thrombotic occlusion of a coronary artery at the site of a ruptured or eroded plaque. Diagnosis is based on characteristic symptoms and electrocardiogram changes, and confirmed subsequently by raised cardiac enzymes. Prognosis is dependent on the size of the infarct, presence of collaterals and speed with which the occluded artery is reopened. Mechanical reperfusion by primary percutaneous coronary intervention is superior to fibrinolytic therapy if delivered by an experienced team in a timely fashion. Post-reperfusion care includes monitoring for complications, evaluation of left ventricular function, secondary preventive therapy and cardiac rehabilitation. PMID- 27251921 TI - New approaches to predicting the risk of sudden death. AB - In this review article, we will explore some of the contemporary methods for predicting sudden cardiac death (SCD). These include experimental methods yet to be adopted in the clinical setting, and methods that have been extrapolated from observational data in those with a history of SCD. We will discuss how these relate to the different aetiologies and disease processes. We will also explore how these may be used in the clinical setting to decide on management. PMID- 27251922 TI - CME Cardiology (100622): self-assessment questionnaire. PMID- 27251923 TI - Lesson of the month 1: Post-malaria neurological syndromes. AB - There are three neurological syndromes that may follow -malarial infection after recovery and at a time when the patient is aparasitaemic. An acute disseminated encephalopathy; a cerebellar syndrome; and an acute demyelinating polyneuropathy. This paper reports a 42-year-old male patient who developed encephalopathy. PMID- 27251924 TI - Lesson of the month 2: Houssay phenomenon - hypopitutarism leading to remission of diabetes. AB - Because of a pituitary insult and the subsequent loss of counter-regulatory hormones, individuals can experience increased sensitivity to insulin, hypoglycaemia or even complete amelioration of diabetes; this is known as the Houssay phenomenon. Severe dehydration following diarrhoea can lead to pituitary infarction causing hypopituitarism. We describe this situation in a patient with insulin-treated type-2 diabetes presenting with recurrent hypoglycaemia and cessation of insulin requirement along with weight loss, hypotension and hyponatraemia. Pituitary imaging revealed a partial empty sella and a synacthen stimulation test revealed an initial positive response but later loss of response, proving recent-onset pituitary dysfunction. Physicians should keep this possibility in mind while treating hypoglycaemia in stable diabetic individuals. Judicious supplementation of deficient hormones is of utmost importance. PMID- 27251925 TI - Image of the month: Alternating bifid pulse - a novel -manifestation of low cardiac output states. PMID- 27251926 TI - Case series of short synacthen tests supports using 9 am cortisol level to exclude adrenal insufficiency. PMID- 27251927 TI - A symptom observation chart to support an individualised approach to care for dying patients in hospital. PMID- 27251928 TI - A cough that doesn't fit the mould. PMID- 27251929 TI - Response. PMID- 27251930 TI - Heart failure - what the general physician needs to know. PMID- 27251931 TI - Embedding comprehensive geriatric assessment in the emergency assessment unit: the impact of the COPE zone. PMID- 27251932 TI - Response. PMID- 27251933 TI - Embedding comprehensive geriatric assessment in the emergency assessment unit: the impact of the COPE zone. PMID- 27251934 TI - Response. PMID- 27251935 TI - Incorrect primer sequences in the article on methylprednisolone treatment. PMID- 27251936 TI - Extrapolating human judgments from skip-gram vector representations of word meaning. AB - There is a growing body of research in psychology that attempts to extrapolate human lexical judgments from computational models of semantics. This research can be used to help develop comprehensive norm sets for experimental research, it has applications to large-scale statistical modelling of lexical access and has broad value within natural language processing and sentiment analysis. However, the value of extrapolated human judgments has recently been questioned within psychological research. Of primary concern is the fact that extrapolated judgments may not share the same pattern of statistical relationship with lexical and semantic variables as do actual human judgments; often the error component in extrapolated judgments is not psychologically inert, making such judgments problematic to use for psychological research. We present a new methodology for extrapolating human judgments that partially addresses prior concerns of validity. We use this methodology to extrapolate human judgments of valence, arousal, dominance, and concreteness for 78,286 words. We also provide resources for users to extrapolate these human judgments for three million English words and short phrases. Applications for large sets of extrapolated human judgments are demonstrated and discussed. PMID- 27251937 TI - Biological invasion by a benthivorous fish reduced the cover and species richness of aquatic plants in most lakes of a large North American ecoregion. AB - Biological invasions are projected to be the main driver of biodiversity and ecosystem function loss in lakes in the 21st century. However, the extent of these future losses is difficult to quantify because most invasions are recent and confounded by other stressors. In this study, we quantified the outcome of a century-old invasion, the introduction of common carp to North America, to illustrate potential consequences of introducing non-native ecosystem engineers to lakes worldwide. We used the decline in aquatic plant richness and cover as an index of ecological impact across three ecoregions: Great Plains, Eastern Temperate Forests and Northern Forests. Using whole-lake manipulations, we demonstrated that both submersed plant cover and richness declined exponentially as carp biomass increased such that plant cover was reduced to <10% and species richness was halved in lakes in which carp biomass exceeded 190 kg ha-1 . Using catch rates amassed from 2000+ lakes, we showed that carp exceeded this biomass level in 70.6% of Great Plains lakes and 23.3% of Eastern Temperate Forests lakes, but 0% of Northern Forests lakes. Using model selection analysis, we showed that carp was a key driver of plant species richness along with Secchi depth, lake area and human development of lake watersheds. Model parameters showed that carp reduced species richness to a similar degree across lakes of various Secchi depths and surface areas. In regions dominated by carp (e.g., Great Plains), carp had a stronger impact on plant richness than human watershed development. Overall, our analysis shows that the introduction of common carp played a key role in driving a severe reduction in plant cover and richness in a majority of Great Plains lakes and a large portion of Eastern Temperate Forests lakes in North America. PMID- 27251939 TI - Are electrophysiological criteria useful in distinguishing childhood demyelinating neuropathies? PMID- 27251938 TI - Subcutaneous vs. intravenous immunoglobulin in CIDP: pharmacokinetic and clinical response. PMID- 27251940 TI - KIR2DL2 and KIR2DS2 as genetic markers to the methotrexate response in rheumatoid arthritis patients. AB - CONTEXT: Disease Modifying Anti-Rheumatic Drugs (DMARDs) are aimed to interfere with rheumatoid arthritis (RA) progression and reduce the joint damage; however, not all patients respond alike. Killer-cell immunoglobulin-like receptors (KIR) and their ligands, human leucocyte antigen class I (HLA-I), have been associated with RA pathology; therefore, KIR and HLA genes may influence the treatment response. MATERIALS AND METHODS: We evaluated the association of KIR genotype and their ligands HLA-C genes with the response to DMARDs in RA patients. We included 69 patients diagnosed with RA and 82 healthy individuals as the reference group. KIR and HLA-C genotyping was performed using SSP-PCR. RA patients were assessed at baseline and under treatment at 6 and 12 months; subsequently classified as responders and non-responders in each time period. We evaluated the association between DMARD response and genes using statistical analysis by using Fisher exact test with Bonferroni correction; results were regarded as statistically significant at p < 0.05. RESULTS: Significant difference was observed in gene frequencies of patients and the reference group, KIR2DL2 was associated with RA (p = 0.031, OR = 2.119). We also observed an association between KIR2DS2 and the response to methotrexate (MTX), moreover, the combination KIR2DL2+/KIR2DS2+ was more frequent in responders to MTX (p = 0.043). DISCUSSION AND CONCLUSIONS: In our results, responders and non-responders to DMARDs showed KIR2DS2 and KIR2DL2 different gene frequencies, therefore, these genes could be used as response predictors to DMARDs treatment. Thus, these genes were also associated with disease severity, as well as the treatment response possibly by the immunoregulatory function of NK cells. PMID- 27251941 TI - The phosphatidylethanolamine derivative diDCP-LA-PE mimics intracellular insulin signaling. AB - Insulin facilitates glucose uptake into cells by translocating the glucose transporter GLUT4 towards the cell surface through a pathway along an insulin receptor (IR)/IR substrate 1 (IRS-1)/phosphatidylinositol 3 kinase (PI3K)/3 phosphoinositide-dependent protein kinase-1 (PDK1)/Akt axis. The newly synthesized phosphatidylethanolamine derivative 1,2-O-bis-[8-{2-(2-pentyl cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE) has the potential to inhibit protein tyrosine phosphatase 1B (PTP1B) and to directly activate PKCzeta, an atypical isozyme, and PKCepsilon, a novel isozyme. PTP1B inhibition enhanced insulin signaling cascades downstream IR/IRS-1 by preventing tyrosine dephosphorylation. PKCzeta and PKCepsilon directly activated Akt2 by phosphorylating at Thr309 and Ser474, respectively. diDCP-LA-PE increased cell surface localization of GLUT4 and stimulated glucose uptake into differentiated 3T3-L1 adipocytes, still with knocking-down IR or in the absence of insulin. Moreover, diDCP-LA-PE effectively reduced serum glucose levels in type 1 diabetes (DM) model mice. diDCP-LA-PE, thus, may enable type 1 DM therapy without insulin injection. PMID- 27251942 TI - Heterogeneous Uptake of Gas-Phase Acetic Acid on the Surface of alpha-Al2 O3 Particles: Temperature Effects. AB - Heterogeneous reactions are thought to play a significant role in the formation of haze, especially in wintertime, which suggests that temperature may affect the heterogeneous formation of organic aerosols. As the most-abundant carboxylic acid in the Earth's atmosphere, we chose acetic acid to study the effect of temperature on its heterogeneous reaction with alpha-Al2 O3 between 248 and 298 K. The products were characterized by in situ DRIFTS, which indicated that lowering the temperature slowed the formation of acetate, but promoted the formation of crystalline acetic acid. Moreover, low temperatures promoted a different reaction mechanism to that at room temperature. Owing to the formation of chain structures at low temperatures, crystalline acetic acid molecules covered the surface active sites on alpha-Al2 O3 , thereby inhibiting the formation of acetate. However, crystalline acetic acid reacted with alpha-Al2 O3 itself in a sequential manner. Furthermore, the reactive uptake coefficients, active energies, and acetic acid lifetimes at different temperatures were investigated. PMID- 27251943 TI - Nebivolol and Endothelial Dysfunction in Patients With Essential Hypertension: A Reputation Saver of beta-Blockers? PMID- 27251944 TI - Microfluidic solutions enabling continuous processing and monitoring of biological samples: A review. AB - The last decade has witnessed tremendous advances in employing microfluidic solutions enabling Continuous Processing and Monitoring of Biological Samples (CPMBS), which is an essential requirement for the control of bio-processes. The microfluidic systems are superior to the traditional inline sensors due to their ability to implement complex analytical procedures, such as multi-step sample preparation, and enabling the online measurement of parameters. This manuscript provides a backgound review of microfluidic approaches employing laminar flow, hydrodynamic separation, acoustophoresis, electrophoresis, dielectrophoresis, magnetophoresis and segmented flow for the continuous processing and monitoring of biological samples. The principles, advantages and limitations of each microfluidic approach are described along with its potential applications. The challenges in the field and the future directions are also provided. PMID- 27251945 TI - Ethylene glycol assisted preparation of Ti(4+)-modified polydopamine coated magnetic particles with rough surface for capture of phosphorylated proteins. AB - The reversible protein phosphorylation is very important in regulating almost all aspects of cell life, while the enrichment of phosphorylated proteins still remains a technical challenge. In this work, polydopamine (PDA) modified magnetic particles with rough surface (rPDA@Fe3O4) were synthesized by introduction of ethylene glycol in aqueous solution. The PDA coating possessing a wealth of catechol hydroxyl groups could serve as an active medium to immobilize titanium ions through the metal-catechol chelation, which makes the fabrication of titanium ions modified rPDA@Fe3O4 particles (Ti(4+)-rPDA@Fe3O4) simple and very convenient. The spherical Ti(4+)-rPDA@Fe3O4 particles have a surface area of 37.7 m(2) g(-1) and superparamagnetism with a saturation magnetization value of 38.4 emu g(-1). The amount of Ti element in the particle was measured to be 3.93%. And the particles demonstrated good water dispersibility. The particles were used as adsorbents for capture of phosphorylated proteins and they demonstrated affinity and specificity for phosphorylated proteins due to the specific binding sites (Ti(4+)). Factors affecting the adsorption of phosphorylated proteins on Ti(4+) rPDA@Fe3O4 particles were investigated. The adsorption capacity of Ti(4+) rPDA@Fe3O4 particles for kappa-casein was 1105.6 mg g(-1). Furthermore, the particles were successfully applied to isolate phosphorylated proteins in milk samples, which demonstrated that Ti(4+)-rPDA@Fe3O4 particles had potential application in selective separation of phosphorylated proteins. PMID- 27251946 TI - Quantification of monosialogangliosides in human plasma through chemical derivatization for signal enhancement in LC-ESI-MS. AB - Gangliosides are found in abundance in the central nervous system of vertebrates. Their metabolic disruption and dysfunction are associated with various neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. In order to improve our understanding of the etiology of these diseases, analytical ganglioside assays with sufficient specificity and sensitivity in relevant biological matrices are required. In the present work we have developed and validated a reverse-phase ultra-performance liquid chromatography (UPLC)/tandem mass spectrometry (MS) method for determining monosialogangliosides GM1, GM2, and GM3 present in human plasma. Compared with our previous method, this method enhanced, by 15 fold, MS responses of the analytes by employing 2-(2 Pyridilamino)-ethylamine (PAEA) & 4-(4, 6-Dimethoxy-1, 3, 5-triazin-2-yl)-4 methylmorpholinium chloride (DMTMM)-based derivatization. The analytes and internal standards were derivatized with PAEA&DMTMM after extraction from plasma using a protein precipitation procedure. They were then purified using liquid liquid partitioning. When the samples were then analyzed by UPLC-MS/MS with a multiple reaction monitoring (MRM) mode, we achieved superior sensitivity and specificity. This method was evaluated for extraction recovery, calibration linearity, precision, accuracy, and lower limit of quantification (LLOQ). The validated method was successfully applied to monitor monosialoganglioside levels in the plasma from patients with GM3 synthase deficiency. With significantly increased sensitivity, we have, for the first time, detected a significant amount of GM3 in the affected patients. PMID- 27251947 TI - A pyrene-benzthiazolium conjugate portraying aggregation induced emission, a ratiometric detection and live cell visualization of HSO3(.). AB - The present study deals with the photophysical property of a pyrene benzthiazolium conjugate R1, as a strong intramolecular charge transfer (ICT) probe exhibiting long wavelength emission in the red region. Unlike traditional planar polyaromatic hydrocarbons whose aggregation generally quenches the light emission, the pyrene based R1 was found to display aggregation-induced emission (AIE) property along with simultaneous increase in its quantum yield upon increasing the water content of the medium. The R1 exhibits high specificity towards HSO3(-)/SO3(2-) by interrupting its own ICT producing there upon a large ratiometric blue shift of ~220 nm in its emission spectrum. The lowest detection limit for the above measurement was found to be 8.90 * 10(-8) M. The fluorescent detection of HSO3(-) was also demonstrated excellently by test paper strip and silica coated TLC plate incorporating R1. The live cell imaging of HSO3(?) through R1 in HeLa cells was studied using fluorescence microscopic studies. The particle size and morphological features of R1 and R1-HSO3(-) aggregates in aqueous solution were characterized by DLS along with SEM analysis. PMID- 27251948 TI - A homogeneous and "off-on" fluorescence aptamer-based assay for chloramphenicol using vesicle quantum dot-gold colloid composite probes. AB - In this work, a novel homogeneous and signal "off-on" aptamer based fluorescence assay was successfully developed to detect chloramphenicol (CAP) residues in food based on the fluorescence resonance energy transfer (FRET). The vesicle nanotracer was prepared through labeling single stranded DNA binding protein (SSB) on limposome-CdSe/ZnS quantum dot (SSB/L-QD) complexes. It was worth mentioning that the signal tracer (SSB/L-QD) with vesicle shape, which was fabricated being encapsulated with a number of quantum dots and SSB. The nanotracer has excellent signal amplification effects. The vesicle composite probe was formed by combining aptamer labeled nano-gold (Au-Apt) and SSB/L-QD. Which based on SSB's specific affinity towards aptamer. This probe can't emit fluoresce which is in "off" state because the signal from SSB/L-QD as donor can be quenched by the Au-aptas acceptor. When CAP was added in the composite probe solution, the aptamer on the Au-Apt can be preferentially bounded with CAP then release from the composite probe, which can turn the "off" signal of SSB/L-QD tracer into "on" state. The assay indicates excellent linear response to CAP from 0.001 nM to 10 nM and detection limit down to 0.3 pM. The vesicle probes with size of 88 nm have strong signal amplification. Because a larger number of QDs can be labeled inside the double phosphorus lipid membrane. Besides, it was employed to detect CAP residues in the milk samples with results being agreed well with those from ELISA, verifying its accuracy and reliability. PMID- 27251949 TI - Radiosynthesis and in vivo Evaluation of Carbon-11 (2S)-3-(1H-Indol-3-yl)-2-{[(4 methoxyphenyl)carbamoyl]amino}-N-{[1-(5-methoxypyridin-2 yl)cyclohexyl]methyl}propanamide: An Attempt to Visualize Brain Formyl Peptide Receptors in Mouse Models of Neuroinflammation. AB - Here, we describe the very first attempt to visualize in vivo formyl peptide receptors (FPRs) in mouse brain by positron emission tomography (PET). FPRs are expressed in microglial cells where they mediate chemotactic activity of beta amyloid peptide in Alzheimer disease and, thus, are involved in neuroinflammatory processes. To this purpose, we have selected (2S)-3-(1H-Indol-3-yl)-2-{[(4 methoxyphenyl)carbamoyl]amino}-N-{[1-(5-methoxypyridin-2 yl)cyclohexyl]methyl}propanamide ((S)-1), that we have previously identified as a potent non-peptidic FPR agonist. (S)-[(11) C]-1 has been prepared in high radiochemical yield. (S)-[(11) C]-1 showed very low penetration of blood-brain barrier and, thus, was unable to accumulate into the brain. In addition, (S) [(11) C]-1 was not able to label FPRs receptors in brain slices of PS19 and APP23 mice, two animal models of Alzheimer disease. Although (S)-[(11) C]-1 was not suitable to visualize FPRs in the brain, this study provides useful information for the design and characterization of future potential PET radioligands for visualization of brain FPRs by PET. PMID- 27251950 TI - Newly identified motifs in Candida albicans Cdr1 protein nucleotide binding domains are pleiotropic drug resistance subfamily-specific and functionally asymmetric. AB - An analysis of Candida albicans ABC transporters identified conserved related alpha-helical sequence motifs immediately C-terminal of each Walker A sequence. Despite the occurrence of these motifs in ABC subfamilies of other yeasts and higher eukaryotes, their roles in protein function remained unexplored. In this study we have examined the functional significance of these motifs in the C. albicans PDR transporter Cdr1p. The motifs present in NBD1 and NBD2 were subjected to alanine scanning mutagenesis, deletion, or replacement of an entire motif. Systematic replacement of individual motif residues with alanine did not affect the function of Cdr1p but deletion of the M1-motif in NBD1 (M1-Del) resulted in Cdr1p being trapped within the endoplasmic reticulum. In contrast, deletion of the M2-motif in NBD2 (M2-Del) yielded a non-functional protein with normal plasma membrane localization. Replacement of the motif in M1-Del with six alanines (M1-Ala) significantly improved localization of the protein and partially restored function. Conversely, replacement of the motif in M2-Del with six alanines (M2-Ala) did not reverse the phenotype and susceptibility to antifungal substrates of Cdr1p was unchanged. Together, the M1 and M2 motifs contribute to the functional asymmetry of NBDs and are important for maturation of Cdr1p and ATP catalysis, respectively. PMID- 27251951 TI - Modification of the pT2 substage classification in prostate adenocarcinoma. AB - The current substage classification of pT2 prostate cancer (AJCC, 7th edition, 2010) into pT2a (unilateral tumors <1/2 of lobe), pT2b (unilateral tumors >=1/2 of lobe), and pT2c (bilateral tumors) is of questionable relevance. Many studies show no difference in prognosis between substages, and incidence of pT2b prostate cancer is low. Other classification systems have been proposed based on tumor volume, as measured by dominant nodule size or tumor percentage. We characterized pT2b tumors and assessed the utility of current pT2 substaging in predicting biochemical recurrence-free survival after radical prostatectomy and compared them with different substaging methods based on tumor volume. Patients with pT2 tumors were selected among patients who underwent radical prostatectomy from 1998 to 2008. Dominant nodule size was dichotomized as <1.6 cm versus >=1.6 cm. Tumor percentage was dichotomized as <=25% versus >25%. Kaplan-Meier analysis and multivariate Cox proportional hazard regression models were used to evaluate pathological parameters predictive of biochemical recurrence-free survival. Of 785 patients who met criteria, 145 (18.5%) were pT2a, 15 (1.9%) were pT2b, and 625 (79.6%) were pT2c. The pT2 substages were not significant predictors of biochemical recurrence-free survival on univariate or multivariate analysis. In a multivariate model, tumor percentage >25% (P=.002) was associated with decreased biochemical recurrence-free survival. In patients with stage pT2 prostate cancer, the current substaging method lacks predictive value for biochemical recurrence free survival after accounting for other pathologic and clinical predictors. However, tumor percentage (<=25% versus >25%) is a promising approach to substaging of pT2 prostate cancer based on its prognostic significance. PMID- 27251952 TI - Association of rs6983267 Polymorphism and Thyroid Cancer Susceptibility: A Systematic Review and Meta-Analysis. AB - BACKGROUND Recent genome-wide association studies have identified rs6983267 polymorphism as a key locus in the 8q24 region associated with multisite cancers. However, the information on its association with thyroid cancer is inconclusive. The aim of this study was to determine whether this locus is a risk factor for susceptibility to thyroid cancer by conducting a meta-analysis. MATERIAL AND METHODS Relevant studies were identified by searching PubMed and Embase databases. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated. RESULTS A total of 4 studies including 2825 cases and 9684 controls were enrolled to this meta-analysis. The pooled data showed the G allele of the rs6983267 polymorphism is a risk factor for susceptibility to thyroid cancer (OR=1.08, 95%CI: 1.02-1.16, P=0.01). Significant associations were also found in homozygote comparison (GG vs. TT: OR=1.17, 95%CI: 1.03-1.33, P=0.02) and dominant model (GG+GT vs. TT: OR=1.13, 95%CI: 1.01-1.26, P=0.03). Borderline significant associations in similar directions were found in the recessive model (GG vs. GT+TT: OR=1.10, 95%CI: 0.99-1.22, P=0.07) and heterozygote comparison (GT vs. TT: OR=1.10, 95%CI: 0.99-1.24, P=0.09). CONCLUSIONS Our meta-analysis shows that the rs6983267 G>T polymorphism might be associated with higher risk of thyroid cancer. Further research with larger sample sizes and full investigation of confounding risk factors is needed to confirm or revise our conclusions. PMID- 27251953 TI - Biomolecule-assisted synthesis of defect-mediated Cd1-xZnxS/MoS2/graphene hollow spheres for highly efficient hydrogen evolution. AB - Moderate efficiency and the utilization of noble metal cocatalysts are the key factors that restrict the large-scale application of photocatalytic hydrogen production. To develop more efficient photocatalysts based on earth abundant elements, either a new material strategy or a fundamental understanding of the semiconductor/cocatalyst interfaces is highly desirable. In this paper, we studied the feasibility of in situ formation of defect-rich cocatalysts on graphene-based photocatalysts. A facile biomolecule-assisted strategy was used to self-assmble Cd1-xZnxS/MoS2/graphene hollow spheres. The defect-mediated cocatalyst and synergetic charge transfer around heterostructured interfaces exhibit a significant impact on the visible-light-driven photocatalytic activity of multicomponent solid solutions. With engineered interfacial defects, Cd0.8Zn0.2S/MoS2/graphene hollow spheres exhibited a 63-fold improved H2 production rate, which was even 2 and 3.8 times higher than those of CdS/MoS2/graphene hollow spheres and Cd0.8Zn0.2S/Pt. Therefore, our research provides a promising approach for the rational design of high-efficiency and low cost photocatalysts for solar fuel production. PMID- 27251954 TI - Genetic surfing, not allopatric divergence, explains spatial sorting of mitochondrial haplotypes in venomous coralsnakes. AB - Strong spatial sorting of genetic variation in contiguous populations is often explained by local adaptation or secondary contact following allopatric divergence. A third explanation, spatial sorting by stochastic effects of range expansion, has been considered less often though theoretical models suggest it should be widespread, if ephemeral. In a study designed to delimit species within a clade of venomous coralsnakes, we identified an unusual pattern within the Texas coral snake (Micrurus tener): strong spatial sorting of divergent mitochondrial (mtDNA) lineages over a portion of its range, but weak sorting of these lineages elsewhere. We tested three alternative hypotheses to explain this pattern-local adaptation, secondary contact following allopatric divergence, and range expansion. Collectively, near panmixia of nuclear DNA, the signal of range expansion associated sampling drift, expansion origins in the Gulf Coast of Mexico, and species distribution modeling suggest that the spatial sorting of divergent mtDNA lineages within M. tener has resulted from genetic surfing of standing mtDNA variation-not local adaptation or allopatric divergence. Our findings highlight the potential for the stochastic effects of recent range expansion to mislead estimations of population divergence made from mtDNA, which may be exacerbated in systems with low vagility, ancestral mtDNA polymorphism, and male-biased dispersal. PMID- 27251955 TI - Association of pre-eclampsia with metabolic syndrome and increased risk of cardiovascular disease in women: A systemic review. AB - BACKGROUND AND OBJECTIVES: Cardiovascular disease (CVD) is the leading cause of death in women globally. Preeclampsia has been linked to increased risk of developing heart disease later in life. The best approach for the prevention of CVD after preeclampsia is yet unclear. Studies assessing CVD risk post preeclampsia have included metabolic risk factors that define the metabolic syndrome (MS). This review quantifies the association between preeclampsia and CVD in the context of metabolic risk factors that define the MS. MATERIALS AND METHODS: PubMed database was searched for relevant articles from 1999 to March 2015. The search phrase was "preeclampsia and MS." After two levels of screening by title and abstract, case-control, cohort, and cross-sectional studies that included at least 50 subjects were selected. RESULTS: Twenty-four articles that reported the prevalence or odds for MS and its components following a history of preeclampsia and the prevalence of preeclampsia in women with prepregnancy MS were selected. A total of 9 case-control, 11 cohort, and four cross-sectional studies were included. The prevalence of MS ranged from 10.9% to 27.3% after a preeclamptic pregnancy. About 88% of the case-control studies showed a statistically significant difference in prevalence of MS post preeclampsia whereas 75% of the cohort studies reported prevalence values >10% for the prevalence of MS post preeclampsia. The odds for developing MS post preeclampsia ranged from 1.23 to 3.60 and 83% of the studies reported an odds ratio >2. The prevalence of developing preeclampsia in women with prepregnancy MS ranged from 26.7% to 45% compared to 4.7% to 17% among controls. CONCLUSION: The prevalence and odds for developing MS after a preeclamptic pregnancy are high suggesting that MS may be involved in the pathogenesis of CVD following preeclampsia. This will provide evidence on the potential health benefits of a modifiable CVD risk screening program for women with a history of preeclampsia. PMID- 27251956 TI - Effects of combined general anesthesia and thoracic epidural analgesia on cytokine response in patients undergoing laparoscopic cholecystectomy. AB - BACKGROUND: Severe postoperative pain is not often experienced in laparoscopic cholecystectomy. Anesthesia, surgery, and pain are stressful and cause different reactions in neuro-immuno-endocrine systems. Many factors such as the pharmacological effect of the drugs used, as well as the type and depth of anesthesia, can affect these reactions. OBJECTIVE: The aim of this study was to evaluate the effect of the combination of general anesthesia and thoracic epidural analgesia (TEA) on cytokine reaction in laparoscopic cholecystectomy. STUDY DESIGN: Prospective, randomized clinical comparative study. MATERIALS AND METHODS: Sixty adult patients scheduled for elective laparoscopic cholecystectomy were divided into four groups. Group saline (Group S), group fentanyl (Group F), group bupivacaine (Group B), and group levobupivacaine (Group L) were infused with saline, saline and fentanyl, bupivacaine and fentanyl, and levobupivacaine and fentanyl, respectively, via epidural catheter before surgical incision. RESULTS: There were no differences among groups in the demographic features, heart rate, mean arterial pressure, and peripheral oxygen saturation values. Group L had lower visual analogue scale value compared to the other postoperative groups (P < 0.01). In all groups, interleukin-6 (IL-6), IL-8, and IL-10 levels started to increase at 2 h and returned to the basal level at 24 h. IL levels increased in most of the epidural saline-administered group compared to other groups (P < 0.05). CONCLUSION: Combined general anesthesia and TEA provided pain control and hemodynamic stability more efficiently during the first 24 h of the intraoperative and postoperative period by suppressing cytokine levels. However, we determined that this effect was more obvious with the local anesthetic and opioid combination. PMID- 27251957 TI - W/M serrated osteotomy for infantile Blount's disease in Ghana: Short-term results. AB - PURPOSE: The W/M serrated high tibial osteotomy is a not frequently described surgical technique for simultaneously correcting the varus and torsional deformity in patients with Blount's disease. Without the need for internal fixation, this surgical treatment is well suited for developing countries. This study describes the short-term results of the bilateral and unilateral W/M serrated osteotomy in patients with infantile Blount's disease. METHODS: Between May 2008 and January 2013, 52 patients were treated with uni- (n = 22) or bi lateral (n = 30) W/M serrated osteotomy of the proximal tibia due to a tibial varus deformity in two district hospitals in Ghana. Other causes than infantile Blount's disease were excluded from the analysis. Pre- and post-operative clinical and radiological measurements were done, and complications were monitored up to 12 weeks after surgery. RESULTS: Seventeen patients (five males, 12 females; mean age 4.9 [standard deviation: 2.10]) were included, which underwent a total of 25 W/M serrated osteotomies. The femorotibial angle was corrected from 34.1 degrees ([mean] range: 6-68 degrees ) to - 7.1 degrees ([mean] range: -28-5 degrees ). Only one patient had developed a wound infection, and all reached full consolidation. CONCLUSIONS: The W/M serrated osteotomy seems a profitable alternative technique for treating the varus and torsional deformity in patients with Blount's disease in the circumstances of developing countries. The short-term outcomes are good and promising with a low complication rate and good consolidation. Long-term follow-up results of these patients are needed to observe possible complications. LEVEL OF EVIDENCE: IV, therapeutic case series. PMID- 27251958 TI - Comparison of Saudi child versus parent-report of child tooth-brushing practices. AB - OBJECTIVE: This cross-sectional study compared Saudi children's tooth-brushing practices as reported by children and parents and then matched the agreement of reports. MATERIALS AND METHODS: A sample of 100 Saudi parents and their children of ages 8-12 years participated in this cross-sectional investigation. A self administered structured questionnaire regarding the current tooth-brushing practice and habits at home was filled by the child. The same questionnaire was filled independently by parents. RESULTS: Mothers were more likely to teach children about tooth-brushing and fathers were minimally helping children during tooth-brushing. Mothers were the first to teach the children and approximately 33% of the children started brushing their teeth by age 5. Children and parents reported that children clean their teeth using a tooth-brush (73.74% and 76.77%), miswak (5.05% and 5.05%), or both (21.21% and 18.18%), respectively. CONCLUSIONS: There was some agreement between reported tooth-brushing practice of children and their parents. It is important to question both the child and parent regarding oral hygiene practice and compare their answers to get more broad knowledge about their practices. Approximately, one-third of the children started brushing their teeth by age 5, which differs from recommended oral hygiene practices. PMID- 27251959 TI - Day surgery is effective and safe for patients with great saphenous vein varices who meet American Society of Anesthesiologists I-II grading. AB - BACKGROUND AND AIM: Since the concept of "Day Surgery"; (DS) was firstly put forward in 1995, DS for great saphenous vein varices (GSVV) becomes more and more dominant in worldwide, but it is accepted only in a limited population in China. Hence in the present retrospective study, patients who received DS and regular surgery are compared to assess the effectiveness and safety of DS for GSVV. PATIENTS AND METHODS: From 2011 to 2013, 452 patients who received DS and 372 patients who received inpatient surgery (IS) were collected from hospital main clinical database. Baseline characteristics, prognosis, and 12-month-long follow up were compared. RESULTS: Mean age in DS group was 52.76 +/- 4.89, 53.42 +/- 5.52 in IS group. During follow-up after surgery, incidence of deep vein thrombosis (DVT), saphenous nerve injury (SNI), wound infection, and recurrence in DS and IS groups was 0.9% versus 0.8%; 2% versus 3%; 3.3% versus 3.8%; and 1.3% versus 1.1%, respectively. Moreover, there was no significant difference in incidence of DVT, SNI, wound infection, and recurrence between groups (P = 0.904; 0.376; 0.719; and 0.742). However, average hospital stays in DS group was 1 day, compared to 4.2 days in IS group. Moreover with respect to average medical cost (dollar), it was 780.33 dollars and 1021.06 dollars in DS and IS group, respectively. CONCLUSION: DS for GSVV is an effective and safe procedure, which was the same as IS. However compared with IS, DS could decrease the average medical cost for patients and hospital stays obviously. Hence DS for GSVV is a win-win procedure for patient and health care. PMID- 27251960 TI - Are blood pressure values compatible with medication adherence in hypertensive patients? AB - BACKGROUND AND AIM: In the management of hypertension (HT), maintaining the medication adherence with treatment is as important as starting treatment. Studies have shown that the majority of patients taking medication do not reach their target values. This study aimed to investigate the relationship between the patient medication adherence and blood pressure (BP) values and reflection to general well-being. MATERIAL AND METHODS: The study included 259 primary HT patients. The patients with BP measurements completed the Medication Adherence Self-Efficacy Scale-Short Form 13 and the World Health Organization-5 (WHO-5) well-being index. A Holter device was attached, and 24 h BP monitoring was completed. RESULTS: The mean points for medication adherence scale was 29.2 +/- 10.3 (1-40) and mean WHO-5 points was 13.7 +/- 4.6 (4-25) for patients. Clinical mean systolic BP was 140.0 +/- 12.6 and diastolic 84.8 +/- 9.0 mm Hg, while 24 h mean BP was systolic 119.5 +/- 10.6 and diastolic 73.3 +/- 8.1 mm Hg. While there was negative correlation between medication adherence scale scores and clinical systolic BP (r = -0.171; P = 0.006), there was no correlation with other BP readings. There was no correlation with the WHO-5 score and clinical readings, though there was a positive correlation between ambulatory mean systolic and diastolic BP (r = 0.141; P = 0.023 and r = 0.123; P = 0.049, respectively). There was positive correlation between the patient's medication adherence scores and the WHO-5 scores (r = 0.141; P = 0.023). CONCLUSION: When clinicians assess medication adherence of patients, they should benefit from objective BP measurements and scales. Subjective and objective findings are important while making clinical decision. PMID- 27251961 TI - The effects of different irrigation protocols on removing calcium hydroxide from the root canals. AB - OBJECTIVE: The aim of this study was to evaluate the efficiencies of different irrigation protocols and solutions in the removal of calcium hydroxide (Ca[OH]2). MATERIALS AND METHODS: Sixty-eight maxillary incisors were used. Root canals were prepared and filled with Ca(OH)2. Two control (n = 4) and six experimental groups (n = 10) were adjusted: Group 1:1% peracetic acid (PAA) + master apical file (MAF); Group 2: 17% ethylenediaminetetraacetic acid (EDTA) + MAF; Group 3: 9% 1 hydroxyethylidene-1,1-bisphosphonate (HEBP) + MAF; Group 4: 1% PAA + ultrasonic activation (UA); Group 5: 17% EDTA + UA; Group 6: 9% HEBP + UA. The cleanliness of root canal thirds were evaluated with scanning electron microscopy. Statistical analysis were performed (alpha = 0.05). RESULTS: At coronal thirds; PAA + UA was superior to EDTA + MAF, HEBP + MAF; and PAA + MAF was superior to EDTA + MAF, HEBP + MAF (P < 0.05). At middle thirds; PAA + MAF and PAA + UA were superior to EDTA + MAF and EDTA + UA; and, PAA + UA was superior to HEBP + MAF (P < 0.05). There were no significant differences among the rest of the experimental groups (P > 0.05). CONCLUSION: Complete removal of Ca(OH)2could not be achieved by none of the irrigants at all root thirds. PMID- 27251962 TI - Prevalence and associations of symptomatic renal papillary necrosis in sickle cell anemia patients in South-Eastern Nigeria. AB - AIM: To assess the prevalence and associations of symptomatic renal papillary necrosis (RPN) in sickle cell anemia patients. PATIENTS AND METHODS: The case notes of homozygous hemoglobin (Hb) S patients diagnosed with RPN were retrospectively assessed. Diagnosis was based on microscopic hematuria and positive ultrasound findings. Their steady state diastolic blood pressure, Hb, leukocyte count, platelet count, serum direct bilirubin, and aspartate transaminase, were obtained by automated analyzers. These were evaluated for any relationship with the occurrence of RPN. RESULTS: Two hundred and twenty patients were assessed aged 6-55 years with a median age of 24 years. The prevalence of symptomatic RPN was found to be 2.3%. RPN was positively associated with the female gender (Chi-square P value 0.001), but not with any other clinical or laboratory variable. However, other predictors of disease severity were positively associated with RPN such as age, diastolic blood pressure 0.180 (P = 0.016), serum aspartate transaminase, serum bilirubin 0.145 (0.027), Hb, and leukocyte count - 0.155 (P = 0.003). CONCLUSION: The prevalence of symptomatic RPN is low in this group of homozygous S patients and occurs more commonly in females. Improvement in care for these patients will reduce these chronic complications. PMID- 27251963 TI - Conventional trans-tibial versus anatomic medial portal technique for femoral tunnel preparation in anterior cruciate ligament reconstruction; comparison of clinical outcomes. AB - AIM: Method of femoral tunnel preparation in anterior cruciate ligament (ACL) reconstruction is controversial. In this study, we aimed to determine if there is any difference between the clinical outcomes of two most commonly used drilling techniques; which are conventional trans-tibial (TT) drilling of femoral tunnel and anatomic preparation of femoral tunnel through medial portal (MP), in patients who underwent ACL reconstruction. MATERIAL AND METHODS: One hundred and twenty-nine male patients who underwent ACL reconstruction between 2010 and 2012 were included in the study. Single-bundle reconstruction with a quadrupled autologous hamstring graft was performed in all patients. Femoral tunnel was drilled by the conventional TT technique in 58 patients (Group 1) and through MP in 71 patients (Group 2). Functional evaluation was made about 12 months postoperatively. Functional evaluation included the Lysholm Knee Scale, International Knee Documentation Committee Scoring (IKDC), and Tegner Activity Level Scale were used for assessment. The anteroposterior stability was assessed using KT-1000 arthrometer and the pivot shift test for assessment of rotational stability. RESULTS: Interval between injury and surgery was similar between two groups (median 8.0 vs. 10 weeks, for TT vs. MP, respectively). One hundred twenty five patients attending the final follow-up examination (96.8%) were evaluated. The results of Lysholm, IKDC, and Tegner scales were found to be similar. According to KT-1000 arthrometer results, MP group revealed slightly better results than TT group. Regarding pivot shift, MP group showed significantly better stability than TT group (P < 0.001). CONCLUSION: The anatomical single bundle femoral tunnel preparation in the reconstruction of the ACL seems as effective as the conventional technique in terms of functional stability in the midterm. The technique better preserved the rotational stability in non professional athletes. PMID- 27251964 TI - Effects of alpha-tocopherol on gingival expression of inducible nitric oxide synthase in the rats with experimental periodontitis and diabetes. AB - BACKGROUND: The aim of this study was to investigate effects of alpha-tocopherol and/or insulin on the number of gingival inducible nitric oxide synthase (iNOS) positive cells in rats with experimental periodontitis with or without streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: A total of 60 Sprague-Dawley rats were divided into three groups: Group I: The group without diabetes; Group II: The group with STZ-induced diabetes; Group III: The group with STZ-induced diabetes receiving insulin therapy. All animals received anesthesia, and 3/0 silk suture was inserted around the mandibular molar teeth. All groups were divided into subgroups receiving saline (Groups IA, IIA, IIIA) and alpha-tocopherol injection (Groups IB, IIB, IIIB). After a period of 3 weeks, all rats were sacrificed, and the number of gingival iNOS positive cells was analyzed using image analysis software. RESULTS: Applying alpha-tocopherol suppressed the number of gingival iNOS positive cells in Groups IB, IIB, and IIIB compared to application of saline (Groups IA, IIA, and IIIA) (P < 0.05). Numbers of gingival iNOS positive cells were found to be similar in the Groups I and III (P > 0.05). CONCLUSIONS: Within limitations of the current study, this is the first study one may suggest that alpha-tocopherol may reduce oxidative damage in the gingiva of the rats with periodontitis with or without STZ-induced diabetes and increase effects of insulin. PMID- 27251965 TI - Salivary glucose as a diagnostic tool in Type II diabetes mellitus: A case control study. AB - BACKGROUND AND OBJECTIVES: The prevalence of diabetes mellitus is increasing steadily in India. Understanding blood glucose level is the key to both diagnosis and management of diabetes mellitus. However, there is an on-going need for improvements in noninvasive, point-of-care tools for the diagnosis and prognosis of diabetes. Assessing a relationship between the blood glucose level and its concentration in other body fluids such as the saliva can help in developing a conservative method for blood sugar assessment replacing venous blood sampling. Diabetes mellitus is known to cause changes in salivary composition. Hence, this study was undertaken to evaluate the relationship of blood glucose level with salivary glucose in diabetic and nondiabetic patients. MATERIALS AND METHODS: The study sample included 100 diabetic patients and 100 nondiabetic patients aged above 35 years of age. Fasting blood and salivary glucose levels were measured in the two groups. Pearson's correlation coefficient was used to assess the correlation of blood glucose with salivary glucose in the two groups. RESULTS: The results of the study revealed an increase in the level of fasting salivary glucose in diabetics compared to that of nondiabetic patients. It also showed a highly significant positive correlation between fasting salivary glucose and serum glucose in both diabetic patients and in controls. CONCLUSION: From this study, it can be concluded that fasting salivary glucose level can be used as a noninvasive diagnostic, as well as a monitoring tool to assess the glycemic status of Type II diabetes mellitus patients. PMID- 27251966 TI - Bacterial contamination of hemodialysis water in three randomly selected centers in South Western Nigeria. AB - BACKGROUND: Hemodialysis (HD) is the most common method of renal replacement therapy for patients with either acute kidney injury in the failure stage or end stage kidney failure in Nigeria. The number of dialysis centers in Nigeria has risen exponentially from 10 centers two decades ago to more than 120 centers in 2015. The number of patients needing renal replacement therapy in the country in the form of HD has also risen close to a projected 2000/year. The outcome from HD in Nigeria is poor as a result of a myriad of interwoven factors such as complications of cardiovascular diseases and suboptimal dialysis dose primarily due to economic factors. These are often complicated by episodes of dialysis water related bacteremia, possibly as a result of the apparent lack of a standardized guideline or protocol for monitoring dialysis water treatment system which is the driving force of dialysis units. OBJECTIVES: This is a multicenter laboratory-based study designed to determine the microbiological quality of samples of HD water and dialysate in randomly selected dialysis units in three major government teaching hospitals in Nigeria. METHODOLOGY: Water samples were aseptically and serially collected from three HD units. The samples were taken from 6 points at each center coded A, B, and C over a 6-month period. RESULTS: The water system in the three dialysis centers were grossly contaminated with Gram-negative aerobic bacteria such as Pseudomonas species and Moraxella species at all the points in the three centers. CONCLUSION: Conventionally, water treatment is a major determinant of morbidity and mortality in HD units, and the microbial quality is a major factor involved. There is evidence of bacterial contamination in the dialysis units sampled in this study. There is thus the compelling need for periodic microbiological monitoring of water after each treatment step. A uniform national guideline as part of an effective quality assurance protocol in infection surveillance is also advocated for dialysis units in Nigeria. PMID- 27251967 TI - Dentists' knowledge of occlusal splint therapy for bruxism and temporomandibular joint disorders. AB - AIMS: The aim of this study was to investigate dentist's approaches to the use of splint therapy for myofascial pain, bruxism, and temporomandibular joint (TMJ) disorders and to assessment of treatment modalities. MATERIALS AND METHODS: A 12 item questionnaire was developed to determine dentists' knowledge of TMJ disorders and approaches for occlusal splint treatments. The researchers spoke with each dentist included in the study at his/her clinic or by telephone to assess their immediate knowledge and approach to the TMJ disorders. Chi-squared test was performed to analyze the values. The confidence interval was set as 95%. RESULTS: A total of 370 dentists working in Turkey were participated in this study. The most common splint application reason for occlusal splint treatment was bruxism (77.8%) while TMJ pain was very rare (%1.4). The use of hard splint ratios for 0-5 years of professional experience was 57.0%, 42.4.0%, and 26.8% for the experience of 5-15 years and over 15 years groups, respectively (P < 0.001). While the dentists' with sufficient knowledge soft splint application rates were 11.6%, hard splint application rates were 43.4% for the dentists with sufficient knowledge. Occlusion adjustment rate of dentists who practice in all three groups was under 16.0%. CONCLUSIONS: The knowledge of the dentists about TMJ disorders and occlusal splint therapy were found to be insufficient. Their knowledge decreased with increasing experience. PMID- 27251968 TI - Physician and nurse knowledge about patient radiation exposure in the emergency department. AB - BACKGROUND: Imaging methods that use ionizing radiation in emergency departments (EDs) have increased with advances in radiological diagnostic methods. Physician and nurse awareness of the radiation dose in the ED and the associated cancer risks to which the patients are exposed were surveyed with a questionnaire. METHODS: A total of 191 subjects in six EDs participated in this study. ED physicians and ED nurses were asked about the risks and the radiation doses of imaging methods ordered in the ED. The differences between the two groups were compared using Student's t-test for continuous variables. A Fisher's exact and Chi-squared tests were used for categorical variables. RESULTS: A total of 82 ED physicians and 109 ED nurses completed the questionnaire; 38 (46.3%) physicians and 8 (7.3%) nurses correctly answered the question about the chest X-ray radiation dose. A question about the number of chest X-rays that is equivalent to the dose of a pelvic X-ray was answered correctly by 5 (6.1%) physicians and 9 (8.3%) nurses (P = 0.571). Questions regarding abdominal computed tomography (CT), chest CT, brain CT, abdominal ultrasonography, and brain magnetic resonance imaging were answered correctly more frequently by the physician group than the nurse group (P < 0.05). The risk of developing cancer over a lifetime due to a brain CT was correctly answered by 21 (25.6%) physicians and 30 (27.5%) nurses (P = 0.170). A similar question regarding abdominal CT was correctly answered by 21 (25.6%) physicians and 42 (38.5%) nurses (P = 0.127). CONCLUSIONS: Knowledge of the radiation exposure of radiology examinations was lower in nurses than physicians, but knowledge was poor in both groups. ED physicians and nurses should be educated about radiation exposure and cancer risks associated with various diagnostic radiological methods. PMID- 27251969 TI - Clinical profile, knowledge, and beliefs about diabetes among patients attending a Tertiary Health Centre in Lagos: A cross-sectional survey. AB - INTRODUCTION: Diabetes affects 347 million people worldwide; more than 80% of the affected live in low- or middle-income countries. Patients' beliefs about their medical conditions are important in helping physician focus on beliefs that needed to be changed or reinforced. The overall aim of this study was to improve the standard of care of patients with diabetes. METHODS: The study designed was a cross-sectional survey; adults with diabetes attending diabetic clinic of LASUTH took part in the survey. Participants were asked to fill a structured questionnaire which was used to assess clinical patterns, beliefs, and practice about diabetes. RESULTS: One hundred and fifty patients with diabetes took part in the study. This study showed that more females presented with diabetes compared with males, type 2 diabetes is commonerthan type 1 and there is a highassociation of the disease with hypertension or being overweight. More than half of the participants do not know the cause of diabetes, 13% believed that disease is curable, and 30% admitted to use alternative medications in addition to the anti-diabetic medications prescribed by the physicians. CONCLUSION: Knowing patients' beliefs and knowledge about diabetes is important to impart overall care for them. Health education about a disease should be planned to address beliefs and knowledge of patients about their medical condition to address misinformation and misconceptions about their disease conditions. PMID- 27251970 TI - The prevalence of cervical ribs in Enugu, Nigeria. AB - BACKGROUND: Cervical rib is an important cause of nontraumatic thoracic outlet neurovascular compression. This study was undertaken as there is no known documented report on its prevalence in the study environment. AIMS: To evaluate the prevalence of cervical ribs and its variation with sex and age among patients presenting at radiological facilities for a chest radiograph. SETTINGS AND DESIGN: Retrospective evaluation of plain posterior-anterior view chest radiographs done in radiological facilities in Enugu, Southeast, Nigeria. SUBJECTS AND METHODS: Evaluated in this study were all 6571 chest radiographs consecutively obtained between 2009 and 2012 in three randomly selected radiological facilities in Enugu. STATISTICAL ANALYSIS USED: SPSS version 17 software was used in data analysis. Chi-square and student t-tests were used to test for the significance of findings at 95% confidence level. RESULTS: This study reports the overall prevalence of cervical ribs as 48 (0.7%) with a significantly higher rate in females 43 (1.1%) when compared to males 5 (0.2%) (P = 0.000). In 27 (0.4%) cases, the cervical ribs were bilateral; whereas in 21 (0.3%) cases, they were unilateral with 8 (0.1%) on the left and 13 (0.2%) on the right. There was no age-related variability with prevalence (P = -0.813). CONCLUSIONS: The prevalence of cervical rib in the study population is low and within the known range as seen in other geographical regions of Nigeria. PMID- 27251971 TI - The histological study of osseous regeneration following implantation of various bone graft biomaterials. AB - BACKGROUND: While various biomaterials are used for bone regeneration, the relative comparative efficiency of them has not been thoroughly investigated. PURPOSE: This study evaluated histopathological events during osseous healing after implantation of following bone grafts: Demineralized freeze-dried cortical bone powder (DFDB), natural coral implants, calcium sulfate-based putty containing demineralized bone matrix (CaS-DBM), and pure-phase beta tricalcium phosphate ceramic granules (beta-TCP). MATERIALS AND METHODS: Fifty-six Wistar Albino rats were used for this study. The postimplantation osseous healing was evaluated at 3rd, 6th weeks after the operation. RESULTS: DFDB did not induce bone formation in 3 weeks period, but it showed a highly osteoinductive effect at the end of 6th week period. The effects of coral implants on bone formation both at 3 and 6 weeks period were much higher than the DFDB. CaS-DBM showed higher bone formation than beta-TCP at 3rd, 6th weeks. It was found that coral and CaS DBM had a more beneficial impact on early bone healing compared to beta-TCP and DFDB. All these graft biomaterials are useable in human bone defects. The main difference in the ossous healing properties of these materials is observed early postimplantation with the delayed healing outcome being similar. PMID- 27251972 TI - The use of special stains in liver biopsy interpretation: Implications for the management of liver disease in Nigeria. AB - CONTEXT: The evaluation of a liver biopsy requires the use of stains other than routine hematoxylin and eosin (H and E) to highlight many important features. AIMS: Most Nigerian Histopathology Departments do not routinely perform special stains (personal communication by authors). This study aims to re-evaluate a set of liver biopsies which has been diagnosed solely on H and E stains by performing a standard set of special stains on them. SETTINGS AND DESIGN: This is a retrospective analysis. MATERIALS AND METHODS: The formalin fixed paraffin embedded blocks of liver biopsies reported in two histopathology laboratories between 2008 and 2013 were retrieved. These were stained with H and E and the following standard special stains for liver tissue histology - Perl's Prussian blue, reticulin, Sirius red, Shikata orcein, and periodic acid-Schiff with diastase. The stained slides were re-analyzed. STATISTICAL ANALYSIS USED: No formal statistical analysis was performed, but results are summarized and tabulated by summary statistics, where appropriate. RESULTS: Seventy-four liver biopsy paraffin blocks were received in the laboratories. Fifty-three (71.6%) were suitable for analysis out of which 51 (68.9%) had their clinical details retrievable. In 29 cases (56.9%), Perl's stain was positive for iron pigment within the hepatocytes with 17 (58.6%) of these being Grade 1, 7 (24.1%) Grade 2, and 5 (17.2%) Grade 3. Shikata orcein revealed hepatitis B viral surface antigen in 15 (29.4%) of the cases while copper-associated protein was demonstrable in 6 (11.8%) of the cases. The discovery of stainable iron implies some degree of disturbance of iron metabolism, and a Grade 3 stainable iron requires investigation for genetic hemochromatosis. The demonstration of copper-associated proteins suggests biliary disease in a noncirrhotic liver which also requires further investigation. CONCLUSION: This study confirms the need to routinely perform special stains in reporting liver biopsies to fully investigate and manage patients and their relatives. PMID- 27251973 TI - Various scoring systems for predicting mortality in Intensive Care Unit. AB - CONTEXT: Various scoring systems have been developed to predict mortality and morbidity in Intensive Care Unit (ICU), but different data has been reported so far. AIMS: This retrospective clinical study aims to evaluate predictability of Acute Physiology and Chronic Health Evaluation II (APACHE II), APACHE IV, Simplified Acute Physiology Score III (SAPS III) scoring systems regarding with mortality. SETTINGS AND DESIGN: Sixteen bed surgical-medical ICU in university hospital. MATERIALS AND METHODS: The study comprised 487 patients older than 18 years treated in ICU for at least 24 h. Age, gender, body weight, initial diagnosis, clinic of referral, intubation, comorbidities, APACHE II, APACHE IV, Glasgow coma scale, SAPS III scores, length of hospitalization before referral to ICU, length of stay in ICU, mechanical ventilation were recorded. RESULTS: Most of the patients (54.6%) were consulted from operating room. The most frequent diagnosis was acute respiratory failure. Total mortality rate was 26%. Mortality rate was higher in patients admitted from wards other than surgery (48%) (P < 0.005). In the presence of comorbidities, mortality rate was higher with comorbidities than without (P < 0.05). Regression analysis indicated a significant positive relationship between length of stay in ICU, length of mechanical ventilation and high mortality risk in patients referred from emergency service (P < 0.05). Accuracy rates of predicting mortality were 81%, 79%, and 81% for APACHE II, APACHE IV, and SAPS III, respectively. CONCLUSIONS: The investigated scoring systems are similar in sensitivity and specificity mortality prediction whereas the accuracy was higher for SAPS III and APACHE II than APACHE III in our patient population. PMID- 27251974 TI - Evaluation of gingival crevicular fluid transforming growth factor-beta1 level after treatment of intrabony periodontal defects with enamel matrix derivatives and autogenous bone graft: A randomized controlled clinical trial. AB - AIM: The present study aimed to evaluate the effects of enamel matrix derivatives (EMD) either alone or combined with autogenous bone graft (ABG) applied to intrabony defects in chronic periodontitis patients on clinical/radiographic parameters and gingival crevicular fluid (GCF) transforming growth factor-beta1 (TGF-beta1) level and to compare with open flap debridement (OFD). MATERIALS AND METHODS: A total of 30 deep intrabony defects in 12 patients were randomly treated with EMD + ABG (combination group), EMD alone (EMD group), or OFD (control group). Clinical parameters, including plaque index, gingival index, bleeding on probing, probing depth, relative attachment level, and recession were recorded at baseline and 6 months postsurgery. Intrabony defect fill percentage was calculated on the standardized radiographs. TGF-beta1 level was evaluated in GCF just before surgery and 7, 14, 30, 90, 180 days after surgery using enzyme linked immunosorbent assay. RESULTS: All treatment procedures led to significant improvements at 6 months (P < 0.01). Gain in attachment level (P < 0.01) and radiographic defect fill (P < 0.05) of the combination and EMD groups were found to be significantly higher than those of the control group, while the use of EMD either with ABG or alone was observed to produce significantly less recession than the OFD (P < 0.05). CONCLUSION: The findings suggest no clinical and radiographic differences between the combination and EMD groups whereas GCF TGF beta1 level demonstrates an increase during the healing phase and is positively affected from EMD. PMID- 27251975 TI - Bilateral concomitant intravitreal anti-vascular endothelial growth factor injection: Experience in a Nigerian tertiary private eye care facility. AB - OBJECTIVES: To evaluate the indication and safety profile of same-session bilateral intravitreal injection of anti-vascular endothelial growth factor (anti VEGF). METHODS: This is a retrospective case series of all the patients that received same-session bilateral intravitreal anti-VEGF in Eye Foundation Hospital, Ikeja, Lagos, from March 2013 to March 2015. Data retrieved from the patients' medical records includes demographics, indications for injections, complications, and systemic comorbidities. RESULTS: During the study period, a total of 442 injections were performed on 126 eyes of 63 patients (M:F ratio; 1.4:1) whose mean age was 55.7 +/- 15.6 standard deviation years. The modal age group was 51-70 years. All the patients received injection Bevacizumab (Avastin; Genentech Inc., South San Francisco, California, USA-1.25 mg). The most common primary indication for initiating bilateral intravitreal therapy was diabetic macular edema 23 (36.5%). Mean follow-up period was 40.6 days (range: 1-364 days). A combined diabetes mellitus and hypertension accounted for most of the systemic comorbidities 28 (44.4%). Subconjunctival hemorrhage was the only complication seen in these patients with 6 (9.5%) occurring intraoperatively and 9 (14.3%) postoperatively. There was no association between intraoperative complication and age (P = 0.66) or gender (P = 0.96). Furthermore, there exist no association between postoperative complication and age (P = 0.49) or gender (P = 0.99). CONCLUSIONS: No major systemic or ocular adverse events were noted. Given that there are potentially serious complications following anti-VEGF injection, further study with a larger number of patients will be necessary to definitively prove the safety of this treatment modality. PMID- 27251976 TI - Riedel's thyroiditis in a black African: A case report and review of literature. AB - Riedel's thyroiditis is a rare cause of the enlargement of the thyroid gland. The etiology is not fully known. There has been no report of Riedel thyroiditis in our country. We report a case of a 61-year-old man with the disease as well as review the literature. We present the case of 61-year-old carpenter seen in our clinic with 21/2 years history of painless anterior neck swelling associated with hoarseness of voice. He had multiple hard nodules on the left lobe of the thyroid gland with multiple cervical lymph nodes enlargement. No feature of hypothyroidism or thyroiditis. Clinical diagnosis of malignant goiter was made although Fine-needle aspiration for cytology did not suggest malignancy. He had surgery, findings included nonresectable hard multinodular left thyroid lobe from which a wedge biopsy was taken, Histology of the specimen revealed Riedel's thyroiditis. He was managed with oral Prednisolone and Tamoxifen with remarkable improvement in his clinical symptoms. Riedel's thyroiditis is a rare disease. It can easily mimic malignant goiter hence proper histological diagnosis will be necessary to differentiate. Review of medical literature showed that Riedel thyroiditis has not been reported in a black African patient inhabiting the sub Sahara Africa. This was a report of Riedel thyroiditis in a black Nigerian patient that was successfully managed on oral glucocorticoid, tamoxifen and L thyroxine. PMID- 27251977 TI - Simultaneous oroantral communication closure, sinus-lifting, and particulate bone grafting and immediate dental implant perforation. AB - The aim of this paper is to introduce an alternative technique for the treatment of oroantral communication (OAC). Closure of OAC, reconstruction of the posterior maxilla by sinus-lifting procedure with a particulate xenograft, and implant insertion were performed in the same operation. A lateral antral approach was used in the sinus elevations. The sinus membranes were elevated gently around the perforation area, and then a barrier membrane was used to close the perforation. Care was taken not to extend the perforation. Next, the maxillary sinus was filled with a particulate xenograft, and an implant was inserted simultaneously. Forty-seven and 40 months of clinical and radiographic follows-up revealed healthy and functional implants in the teeth area. PMID- 27251978 TI - Tension pneumoventricle: A report of two cases. AB - Pneumocephalus is often a complication of head trauma and cranial surgeries. Massive intraventricular pneumocephalus is an uncommon entity. We report the cases of two patients presenting same day with a clinical diagnosis of open head injury following separate road traffic accidents whose computed tomography (CT) brain images confirm skull base and vault fractures with massive pneumocephalus and tension pneumoventricles. CT scan remains invaluable in proper evaluation of head injury, and its complications for early and appropriate intervention toward reducing morbidity and mortality. PMID- 27251979 TI - Concomitant gentamicin-induced nephrotoxicity and bilateral ototoxicity. AB - Co-occurrence of aminoglycoside-induced ototoxicity and nephrotoxicity is rare, possibly as a result of divergent mechanisms of tissue damage despite similarities in the anatomy of the inner ear and the proximal renal tubular epithelium. We present the case of a 63-year-old hypertensive woman who developed nonoliguric acute exacerbation of chronic renal failure and sudden onset of sensorineural deafness after receiving daily injections of gentamicin. Coexisting ototoxicity and nephrotoxicity from aminoglycosides can occur, though rare. Adverse effects of aminoglycosides are better prevented by a careful exercise of discretion by prescribers. PMID- 27251980 TI - Endoprosthetic replacement of distal femoral tumors in Nigeria: A case series. AB - In this observational study, three consecutive patients who were treated for distal femur tumours using endoprosthetic replacement between June 2013 and June 2014 were studied. The patients were within the ages of 28-47 years at the time of surgery. All three patients had modular endoprosthesis fixation and were evaluated using the Musculoskeletal Tumour Society (MSTS) Scoring System. Numerical values from 0 to 5 points were assigned for each of the following 6 categories: pain, function, emotional acceptance, use of supports, walking ability and gait. These values were added and the functional score was presented as a percentage of the maximum possible score. The results for each patient were graded according to the following scale: Excellent - 75-100%; good - 70-74%; moderate - 60-69%; fair - 50-59% and poor - <50%. Of the 3 patients evaluated, 2 had a diagnosis of Giant Cell Tumour (GCT) of the distal femur; the third patient was diagnosed to have plasmacytoma. All underwent wide local resection with modular endoprosthetic distal femur reconstruction. The MSTS functional scores calculated were 70%, 78%, and 52% respectively. Complications noted included wound dehiscence in two patients and thrombosis of the Pulmonary artery needing an arterial embolectomy in one of these two patients. The same patient also had a post-operative loss of motor and sensory function below the level of the ankle. PMID- 27251981 TI - Utilizing Nontraditional Data Sources for Near Real-Time Estimation of Transmission Dynamics During the 2015-2016 Colombian Zika Virus Disease Outbreak. AB - BACKGROUND: Approximately 40 countries in Central and South America have experienced local vector-born transmission of Zika virus, resulting in nearly 300,000 total reported cases of Zika virus disease to date. Of the cases that have sought care thus far in the region, more than 70,000 have been reported out of Colombia. OBJECTIVE: In this paper, we use nontraditional digital disease surveillance data via HealthMap and Google Trends to develop near real-time estimates for the basic (R) and observed (Robs) reproductive numbers associated with Zika virus disease in Colombia. We then validate our results against traditional health care-based disease surveillance data. METHODS: Cumulative reported case counts of Zika virus disease in Colombia were acquired via the HealthMap digital disease surveillance system. Linear smoothing was conducted to adjust the shape of the HealthMap cumulative case curve using Google search data. Traditional surveillance data on Zika virus disease were obtained from weekly Instituto Nacional de Salud (INS) epidemiological bulletin publications. The Incidence Decay and Exponential Adjustment (IDEA) model was used to estimate R0 and Robs for both data sources. RESULTS: Using the digital (smoothed HealthMap) data, we estimated a mean R0 of 2.56 (range 1.42-3.83) and a mean Robs of 1.80 (range 1.42-2.30). The traditional (INS) data yielded a mean R0 of 4.82 (range 2.34-8.32) and a mean Robs of 2.34 (range 1.60-3.31). CONCLUSIONS: Although modeling using the traditional (INS) data yielded higher R estimates than the digital (smoothed HealthMap) data, modeled ranges for Robs were comparable across both data sources. As a result, the narrow range of possible case projections generated by the traditional (INS) data was largely encompassed by the wider range produced by the digital (smoothed HealthMap) data. Thus, in the absence of traditional surveillance data, digital surveillance data can yield similar estimates for key transmission parameters and should be utilized in other Zika virus-affected countries to assess outbreak dynamics in near real time. PMID- 27251984 TI - Effects of three pro-nuclei (3PN) proportion incidence on clinical outcomes of patients with lower retrieved oocytes in the fresh cleavage-stage embryo transfer (ET) cycles. AB - PURPOSE: To analyze the three pro-nuclei (3PN) incidence on clinical outcomes of patients with lower retrieved oocytes in the fresh cleavage-stage embryo transfer (ET) cycles. METHODS: This study included 1200 fresh cleavage-stage ET cycles from January 2013 to June 2015. The patients were divided into 3PN = 0% (773 cycles) and 3PN > 0% (427 cycles) group. Main outcomes compared were fertilization, cleavage, normal fertilization, good quality embryo, implantation, clinical pregnancy, and early abortion rate. RESULTS: We observed that there was no significant difference in female's age, the number of retrieved oocytes, the number of transferred embryos, the number of good quality embryos, endometrial thickness, infertile time, basal serum follicle-stimulating hormone, and E2 value between two groups (p > 0.05). The fertilization (89.43 versus 83.90%, p < 0.001) and cleavage (98.34 versus 97.19%, p = 0.048) rates were significantly higher in 3PN > 0% than 3PN = 0% group. However, the normal fertilization (70.05 versus 50.67%, p < 0.001), good quality embryos (37.11 versus 26.47%, p < 0.001), and clinical pregnancy (49.81 versus 43.79%, p = 0.046) rates were significantly higher in 3PN = 0% than 3PN > 0% group. The implantation (35.88 versus 33.78%, p = 0.333) and early abortion (8.83 versus 10.70%, p = 0.474) rates were not significantly different between two groups. CONCLUSION: 3PN incidence might make a negative effect on clinical outcomes for patients with lower retrieved oocytes in the fresh cleavage-stage ET cycles. PMID- 27251982 TI - 4D printing smart biomedical scaffolds with novel soybean oil epoxidized acrylate. AB - Photocurable, biocompatible liquid resins are highly desired for 3D stereolithography based bioprinting. Here we solidified a novel renewable soybean oil epoxidized acrylate, using a 3D laser printing technique, into smart and highly biocompatible scaffolds capable of supporting growth of multipotent human bone marrow mesenchymal stem cells (hMSCs). Porous scaffolds were readily fabricated by simply adjusting the printer infill density; superficial structures of the polymerized soybean oil epoxidized acrylate were significantly affected by laser frequency and printing speed. Shape memory tests confirmed that the scaffold fixed a temporary shape at -18 degrees C and fully recovered its original shape at human body temperature (37 degrees C), which indicated the great potential for 4D printing applications. Cytotoxicity analysis proved that the printed scaffolds had significant higher hMSC adhesion and proliferation than traditional polyethylene glycol diacrylate (PEGDA), and had no statistical difference from poly lactic acid (PLA) and polycaprolactone (PCL). This research is believed to significantly advance the development of biomedical scaffolds with renewable plant oils and advanced 3D fabrication techniques. PMID- 27251985 TI - The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice. AB - In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280 320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm(-2)) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF kappaB, TNF-alpha, IL-6, COX-2, VEGF, TGF-beta1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis. PMID- 27251986 TI - A method for measuring rotation of a thermal carbon nanomotor using centrifugal effect. AB - A thermal nanomotor is relatively easy to fabricate and regulate as it contains just a few or even no accessory devices. Since the double-wall carbon nanotube (CNT)-based rotary nanomotor was established in a thermostat, assessment of the rotation of the rotor (inner tube) in the stator (outer tube) of the nanomotor has been critical, but remains challenging due to two factors: the small size of the rotor (only a few nanometers) and the high rotational frequency ("1 GHz). To measure the rotation of the nanomotor, in the present study, a probe test method is proposed. Briefly, the rotor is connected to an end-tube (CNT) through a graphene (GN) nanoribbon. As the CNT-probe is on the trajectory of the end-tube which rotates with the rotor, it will collide with the end-tube. The sharp fluctuation indicating the probe tip deflection can be observed and recorded. As a curly GN by hydrogenation is adopted for connecting the rotor and the end-tube, collision between the end-tube and the probe tip occurs only when the centrifugal force is higher than a threshold which can be considered as the rotational frequency of the rotor being measured by the present method. PMID- 27251987 TI - Exploring the optimal pre-sintering temperature on compressive strength and anti fatigue property of graded zirconia-based glass/zirconia structure. AB - To explore the optimal pre-sintering temperature for graded glass/zirconia material, glass/zirconia specimens were prepared and pre-sintered at 900, 1,000 and 1,100 degrees C respectively, glass infiltration and densification at 1,450 degrees C. Monolith Y-TZP specimens were sintered at 1,450 degrees C. Nanoindentation was used to test Young's modulus and Hardness. Compressive strength test and cycling fatigue test were conducted. Nanoindentation test showed graded change of Young's modulus in glass/zirconia structure. The compressive strength and the number of cycles to failure of specimens pre sintered at 1,000 degrees C were significantly higher than those of Y-TZP and the specimens pre-sintered at 900 and 1,000 degrees C (p<0.05). It is concluded that when the pre-sintering temperature is set at 1,000 degrees C, the graded glass/zirconia structure exhibits the most optimal compressive strength and anti fatigue property. PMID- 27251988 TI - Adhesion of different resin cements to enamel and dentin. AB - The purpose of this in vitro study was to compare the shear bond strength (SBS) of five different resin cements to human enamel and dentin under different storage conditions. Five resin cements and their dedicated systems were tested. Teeth were embedded, ground flat to expose enamel or dentin and polished with sandpaper. Adhesive systems were applied according to the manufacturers'instructions. V2A steel cylinders with were silicated, coated, and cemented onto the teeth. Specimens were stored at three different conditions and subsequently thermocycled. SBS was measured. Significant differences were observed between the tested resin cements depending on the tooth surface. Different storage conditions influenced the bond strength, independent of the tooth surface, in all test cements. The bond strength of all experimental materials to enamel is higher than that to dentin surfaces. Furthermore, the adhesiveness decreases after wetness (hydro-) and hydrothermal stress, regardless of the tooth surface. PMID- 27251989 TI - Optical properties of supra-nano spherical filled resin composites compared to nanofilled, nano-hybrid and micro-hybrid composites. AB - This study aimed to evaluate and compare the optical properties of supra-nano spherical filled resin composites and the nanofilled, nano-hybrid and microhybrid composites using the Kubelka-Munk Theory. Diffuse reflectance of samples (Shade A2) was measured against white and black backgrounds, using a spectroradiometer, using a viewing booth with D65 illuminant and d/0o geometry. S and K coefficients and T were calculated using Kubelka-Munk's equations. The spectral behavior of S, K and T was similar for all dental resin composites analyzed (VAF close to 100%), even though they were, generally, statistically different (p<=0.05). The K-M T values overestimate the real value of Transmittance of the resin composites. Supra-nano spherical filled resin composites show the highest scattering and Transmittance when compared with the others materials, probably due to the shape and size of the filler. Such difference should be taken into consideration in a clinical situation to reproduce natural esthetic restorations. PMID- 27251990 TI - Effect of thermocycling on the durability of etch-and-rinse and self-etch adhesives on dentin. AB - The objective was to compare bond strengths of adhesives with/without thermocycling and to analyze the micromorphology of resindentin interfaces. Flat dentin surfaces were prepared and divided into eight groups to bond with four etch-and-rinse adhesives (Optibond FL, Adper Scotchbond Multi-Purpose, Optibond Solo Plus, and Single Bond 2) and four self-etch adhesives (Clearfil SE Bond, Adper SE Plus, Clearfil S(3) Bond and Adper Easy Bond). Specimens were further divided into two subgroups subjected for with/without thermocycling and then subjected to both micro-tensile test and resin-dentin interface evaluation. The results revealed that there were significant differences in bond strength between the groups with and without thermocycling for all etch-and-rinse groups and for the Adper Easy Bond self-etch group (p<0.01). Clearfil SE Bond demonstrated highly durable bond strengths. Furthermore, more silver ion uptake was observed at the resin-dentin interfaces for all etch-and-rinse adhesives and Adper SE Plus and Adper Easy Bond after thermocycling. PMID- 27251991 TI - Stress relieving behaviour of flowable composite liners: A finite element analysis. AB - The purpose of this study was to investigate the consequences of using flowable composite as a liner beneath class I resin composite restorations on polymerization shrinkage stress and occlusal force. Models of class I resin composite restorations were generated. A control model received no flowable composite liner. Thirteen test models received different flowable composite liners with varying elastic modulus. Finite element analysis was used. The polymerization shrinkage of the resin composite and an occlusal force were simulated in the models. The stress and strain energy density in each model were investigated. The results demonstrated that all flowable composite linings were able to reduce polymerization shrinkage stress and occlusal force in enamel, dentin, the hybrid layer, and the adhesive layer to various degrees in tooth restoration systems. Therefore, additional techniques may be applied to reduce the remaining stress and to ensure the long-term success of restorations. PMID- 27251992 TI - Comparison of the surface roughness of feldspathic porcelain polished with a novel alumina-zirconia paste or diamond paste. AB - This study compared the surface roughness of feldspathic porcelain polished with newly developed alumina-zirconia pastes or diamond paste. Porcelain discs were prepared and polished with sandpaper using a polishing-machine. The surface roughness (Ra) of each sample was measured using a profilometer. The samples were randomly divided into 6 groups (n=10). The control group was polished with diamond paste (DP), and the five remaining groups were polished with the newly developed alumina-zirconia paste with the following ratios of glycerin:alumina:zirconia by weight: 1:0.5:0.5 (Z0.5), 1:0.5:0.75 (Z0.75), 1:0.5:1 (Z1), 1:0.5:1.5 (Z1.5), and 1:0.5:2 (Z2). The specimens were polished for 120 s. The Ra values were determined again and the surface morphology of the porcelain samples was analyzed using SEM. The Ra values decreased as the amount of zirconia in the polishing paste increased, except for the Z2 group. The surface roughness as observed by SEM showed a correlation with the Ra values. PMID- 27251993 TI - Bond performance of "Touch and Cure" adhesives on resin core systems. AB - The purpose of this study was to compare the micro-tensile bond strength (uTBS) of three resin core composites to dentin and to examine the bonded interface of the composites. One experimental TDK-03(TD) and, two commercial, DC core Automix One (DC) and Unifil core EM(UN) were used. Flat dentin surfaces of human molars were exposed using #600 SiC paper and bonded with the respective adhesive of each system. After bonding, the composites were built up on the surfaces and cured under two conditions: "light condition" or "dark condition". uTBSs (MPa) in the light condition were: TD; 60.02+/-17.08, DC; 38.21+/-13.70, and UN; 29.50+/-9.71; in the dark condition: TD; 54.62+/-17.11, DC; 8.40+/-4.81, and UN; 9.47+/-6.56. Dark curing negatively affected the bond strength of the two commercial resin core materials. The experimental material was not affected by the curing conditions. PMID- 27251994 TI - Synthesis, biocompatibility and mechanical properties of ZrO2-Al2O3 ceramics composites. AB - This study evaluated cell viability, microhardness and flexural strength of two ceramic composites systems (ZA and AZ), pure alumina and zirconia. There were prepared homogeneous mixtures of 78wt%Al2O3+20wt%3Y-TZP+2wt%Al2O3w (AZ) and 80wt%3YTZP+18wt%Al2O3+2wt%Al2O3w (ZA), as well as 3Y-TZP (Z), pure Al2O3 (A) and commercial monolithic 3Y-TZP (Zc). Also mouse fibroblast cells 3T3-L1 and a MTT test was carried out at 24, 48 and 72 h. The surfaces were observed with SEM and the microhardness and three-point flexural strength values were estimated. The absolute microhardness values were: A>AZ>Z>Zc>ZA. Flexural strength of Zc, Z, and ZA were around double than AZ and A. All groups showed high biocompatibility trough cell viability values at 24, 48 and 72 h. Factors like grain shape, grain size and homogeneous or heterogeneous grain distributions may play an important role in physical, mechanical and biological properties of the ceramic composites. PMID- 27251995 TI - In vitro assessment of a calcium-fluoroaluminosilicate glass-based desensitizer for the prevention of root surface demineralization. AB - The purpose of this study was to evaluate the ability of a calcium fluoroaluminosilicate glass-based desensitizer (Nanoseal) to protect against root demineralization in vitro. Nanoseal was applied to human root dentin, which was immersed in acidic buffer for 72 h, or exposed to pH cycling by immersing in distilled water or mineralizing solution for 24 h intermediately during 48 h-acid attack. Demineralization was evaluated by MU-CT, and mineral loss (ML) and lesion depth (LD) were determined from mineral density profiles. ML and LD in all treatment groups were significantly smaller compared with control. The Nanoseal treated group with pH cycling using mineralizing solution had the lowest ML and LD. Analysis using an EPMA demonstrated calcium and phosphorous were incorporated into the superficial layer of specimens in the Nanoseal-treated groups, suggesting Nanoseal modified the dentin surface, making it resistant to demineralization. Application of Nanoseal is an effective method for protecting root from demineralization. PMID- 27251996 TI - Bonding of flowable resin composite restorations to class 1 occlusal cavities with and without cyclic load stress. AB - To examine the bonding of flowable resin composite restorations (F-restoration) to class 1 occlusal cavities with and without cyclic load stress, compared with that of a universal resin composite restoration (U-restoration). Two flowable composites and one universal composite (control) were applied with an adhesive system to 42 standardized class 1 occlusal cavities. The restored specimens were subjected to cyclic load stress and no stress modes. The microtensile bond strength (MU-TBS) of the dentin floor was measured. The U-restoration did not show pretesting failure. The F-restorations exhibited pretesting failure, regardless of the stress mode. The MU-TBS was not significantly different among the three restorations, regardless of the stress mode. The cyclic load stress did not influence the MU-TBS of the F-restorations; however, it significantly reduced MU-TBS in the U-restoration. The bonding reliability of the F-restorations was inferior to that of the U-restoration, for both stress modes. PMID- 27251997 TI - Mechanical properties, volumetric shrinkage and depth of cure of short fiber reinforced resin composite. AB - The mechanical properties, volumetric shrinkage and depth of cure of a short fiber-reinforced resin composite (SFRC) were investigated in this study and compared to both a bulk fill resin composite (BFRC) and conventional glass/ceramic-filled resin composite (CGRC). Fracture toughness, flexural properties, volumetric shrinkage and depth of cure of the SFRC, BFRC and CGRC were measured. SFRC had significantly higher fracture toughness than BFRCs and CGRCs. The flexural properties of SFRC were comparable with BFRCs and CGRCs. SFRC showed significantly lower volumetric shrinkage than the other tested resin composites. The depth of cure of the SFRC was similar to BFRCs and higher than CGRCs. The data from this laboratory investigation suggests that SFRC exhibits improvements in fracture toughness, volumetric shrinkage and depth of cure when compared with CGRC, but depth of cure of SFRC was similar to BFRC. PMID- 27251998 TI - Effect of thermal cyclic stress on acid resistance of resin-infiltrated incipient enamel lesions in vitro. AB - This study aimed to examine the effect of thermal cycling on gap formation at the interface between infiltrated resin (ICON((r))) and enamel lesion and on the durability of anti-demineralization efficacy to predict the future performance. SS-OCT technique was examined to determine whether it has the potential to detect the gap. Bovine enamel lesions were prepared, and the infiltrated resin was applied to the lesion. Resin-infiltrated lesion specimens were thermal cycled 10,000 cycles and further demineralized in pH 4.5 buffer for 7 days. Released Ca (mg/cm(2)) was quantified by Ca electrode. The SS-OCT technique was applied to detect the gap, and SEM observation was performed to determine the presence of the gap. There was no significant difference in the amount of Ca release before and after the thermal cycling, suggesting long-lasting anti-demineralization efficacy of the resin. SS-OCT and SEM observations indicated no apparent gap formation after the thermal cycling. PMID- 27251999 TI - Assessment of occlusal fissure depth and sealant penetration using optical coherence tomography. AB - Swept source optical coherence tomography (SS-OCT) is an interferometric imaging technique. This study aimed to assess SS-OCT as a diagnostic tool for the evaluation of occlusal fissure depth and sealant penetration into fissure. Seventy investigation sites of occlusal fissures without visible evidence of caries were categorized into four groups (smooth, shallow, intermediate, and deep fissures). Categorization utilized two methods: 1) visually, using a computer screen, and 2) using SS-OCT images. After sealant placement, penetration was observed in SS-OCT. The results obtained from SS-OCT and visual inspections were compared with those of confocal laser scanning microscope (CLSM). The diagnostic power of SS-OCT was higher than that of visual inspection for fissure depth. Additionally, clear cross-sectional images of sealant penetration into fissures were observed with SS-OCT. SS-OCT can be used to evaluate fissure depth and monitor sealant penetration. PMID- 27252000 TI - The pH effect of solvent in silanization on fluoride released and mechanical properties of heat-cured acrylic resin containing fluoride-releasing filler. AB - This study aimed to evaluate the effect of an acidic-adjusted pH of solvent in silanization on the amount of fluoride released and mechanical properties of heat cured acrylic resin containing a silanized fluoride-releasing filler. The experimental groups were divided into 4 groups; non-silanized, acidic-adjusted pH, non-adjusted pH, and no filler as control. For fluoride measurement, each specimen was placed in deionized water which was changed every day for 7 days, every week for 7 weeks and measured. The flexural strength and flexural modulus were evaluated after aging for 48 h, 1, and 2 months. Two-way ANOVA indicated significant differences among groups, storage times, and its interaction in fluoride measurement and flexural modulus. For flexural strength, there was significant difference only among groups. Acidic-adjusted pH of solvent in silanization enhanced the amount of fluoride released from acrylic resin, while non-adjusted pH of solvent exhibited better flexural strength of acrylic resin. PMID- 27252001 TI - A comparative study of marginal fit of copings prepared with various techniques on different implant abutments. AB - This study evaluated fabrication techniques of recently introduced all-ceramic copings' marginal adaptation on two different implant abutments with different finish lines. Five different copings were prepared (Casted chrome-cobalt metal coping, Zirkonzahn, Cercon, In Ceram Alumina and IPS e.max Press) on two cementable implant abutments with two marginal designs. Ten samples for each coping group were prepared (totally 100 samples). Copings were cemented to implant abutments and marginal gap measurements were done from 24 points with stereomicroscope and the datas were analyzed by the Kruskal-Wallis test before cementation. Cercon copings showed the lowest marginal fit scores and metal copings showed the highest scores. After cementation, all marginal gap values have been increased. All marginal gap values obtained from crown copings can be considered in clinically acceptable limits (<120 um) except metal copings after cementation on abutment with 135 degrees shoulder group (123 um). PMID- 27252002 TI - Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects. AB - The aim of this study was to examine the effects of recombinant human BMP-9 (rhBMP-9) with chitosan sponge (ChiS) or absorbable collagen sponge (ACS) on bone formation in rat calvarial defects. The defects were treated by one of the following implantations: ChiS, rhBMP-9/ChiS, ACS, rhBMP-9/ACS and no implantation. The animals were euthanized at 8 weeks for histological evaluation. The percentage of defect closure (DC) in the rhBMP-9/ACS group was significantly greater than that in the ACS group. The rhBMP-9/ACS group demonstrated the highest level of DC among all the groups. The newly formed bone area (NBA) and NBA/total area in the ChiS-implanted groups and in the rhBMP-9/ACS group were significantly greater compared with those in the ACS group. It can be concluded that rhBMP-9/ACS has a potential to induce bone formation in rat calvarial defects. Further studies are required to elucidate the mechanism of bone formation induced by rhBMP-9. PMID- 27252003 TI - Shear bond strengths of an indirect composite layering material to a tribochemically silica-coated zirconia framework material. AB - This study evaluated shear bond strengths of a layering indirect composite material to a zirconia framework material treated with tribochemical silica coating. Zirconia disks were divided into two groups: ZR-PRE (airborne-particle abrasion) and ZR-PLU (tribochemical silica coating). Indirect composite was bonded to zirconia treated with one of the following primers: Clearfil Ceramic Primer (CCP), Clearfil Mega Bond Primer with Clearfil Porcelain Bond Activator (MGP+Act), ESPE-Sil (SIL), Estenia Opaque Primer, MR. Bond, Super-Bond PZ Primer Liquid A with Liquid B (PZA+PZB), and Super-Bond PZ Primer Liquid B (PZB), or no treatment. Shear bond testing was performed at 0 and 20,000 thermocycles. Post thermocycling shear bond strengths of ZR-PLU were higher than those of ZR-PRE in CCP, MGP+Act, SIL, PZA+PZB, and PZB groups. Application of silane yielded better durable bond strengths of a layering indirect composite material to a tribochemically silica-coated zirconia framework material. PMID- 27252004 TI - Bone augmentation around a dental implant using demineralized bone sheet containing biologically active substances. AB - This study was designed to evaluate the volume of alveolar bone augmentation after immediate implant placement using demineralized bone. We examined the collagen matrix of demineralized bone and biologically active substances contained therein. Rat maxillary first molars were extracted, and the animals were divided into five groups as follows: tooth extraction only, implant into the mesial root socket, implant and other root sockets covered with demineralized bone sheet, implant and other root sockets filled with demineralized bone powder under the sheet, and implant and other root sockets covered with demineralized bone sheet from which proteins were extracted. We ascertained whether biologically active substances are contained in extracted proteins. Biologically active substances were detected in extracted proteins. Conditions using demineralized bone sheet with biologically active substances significantly augmented the height of the alveolar bone. Such resorbable membranes containing biologically active substances hold promise as clinical agents for bone augmentation upon implantation. PMID- 27252005 TI - Effect of an experimental adhesive resin containing multi-ion releasing fillers on direct pulp-capping. AB - The purpose of this study was to evaluate pulpal healing and reparative dentin formation after 14 and 28 days in exposed rat pulp directly capped with an experimentally developed all-in-one adhesive containing surface reaction-type pre reacted glass-ionomer (S-PRG) filler. The four experimental groups and the control group were compared using the Kruskal-Wallis test, followed by the Steel Dwass post-hoc test to compare the histopathological score. The Mann-Whitney U test was used to compare the histopathological score at 14 and 28 days for each observation item. All experimental adhesives containing S-PRG fillers developed for direct pulp capping showed no pulpal inflammation. After 14 days, the experimental adhesives containing S-PRG fillers and the control group formed tertiary dentin around the exposed pulp. After 28 days, the experimental adhesives containing 13 and 27 wt% of S-PRG fillers formed dentin bridge equal to the control. PMID- 27252006 TI - Shear bond strength and microleakage of a self-etching adhesive for fissure sealing after different types of aging. AB - The aim of this study was to evaluate shear bond strength (SBS) and microleakage of a self-etching adhesive (Adper Prompt L-Pop) in comparison to acid etching prior fissure sealing. Each procedure was tested with 3 aging procedures (1-day water storage, 3-month water storage and 1-day water storage/5,000* thermocycling). SBS was determined according to ISO standard 29022. Additional 30 third molars were utilized for the microleakage analyses. Data were analyzed using Mann-Whitney-U-Test and multiple linear regression models. The SBS of the self-etching adhesive were significantly lower (14.9, 11.9, and 13.0 MPa) than those of conventional fissure sealing (19.1, 18.2, and 15.6 MPa). Multiple linear regression models predicted that material and alteration significantly influenced SBS. The microleakage revealed no difference between both groups (1.3% vs. 1.2%). It can be concluded that the selfetching adhesive might be a pre-treatment alternative for fissure sealing in terms of the easier and shorter clinical workflow. PMID- 27252007 TI - Fracture resistance of palatal cusps defective premolars restored with polyethylene fiber and composite resin. AB - The aim of the study was to compare the fracture resistance of the palatal cusps of defective and endodontically treated premolars after restoration with various restorative techniques. Fifty premolars were assigned to five groups. The first group comprised intact teeth as control (G1), while the other experimental groups (G2, G3, G4 and G5) comprised endodontically-treated teeth, whose palatal cusps were cut and reduced the buccal cusps by 2 mm. G2, composite resin onlay with buccal cusp coverage (CR). G3, CR and fiber post. G4, CR and polyethylene fiber. G5, CR, fiber post and polyethylene fiber. Fracture resistance was tested. The data were recorded in Newton and submitted to ANOVA and Tukey post hoc tests. Statistically significant difference was found between the mean fracture resistances of the groups. Polyethylene fiber reinforced composite restorations strengthened the fracture resistance of palatal cusps defective and endodontically treated premolars. PMID- 27252008 TI - Depth of cure of contemporary bulk-fill resin-based composites. AB - This study evaluated the depth of cure (DOC) of packable and flowable bulk-fill resin-based composites (RBCs) including PRG (prereacted glass ionomer) and short fiber materials. The materials were placed in a black split-mold with a 7 mm deep recess and cured at 700 mW/cm(2) for 20 s using a LED curing light. DOC was assessed using the ISO scraping and Knoops hardness tests. Data (n=5) were computed and analyzed using one-way ANOVA/Scheffe's post hoc test (p<0.05). ISO DOC ranged from 3.66 to 2.54 mm while DOC based on hardness testing ranged from 3 to 1.5 mm. For all materials, a decrease in hardness was observed with increasing depths. The DOC of bulk-fill RBCs was product dependent and greater than standard composites. At 4 mm depth, none of the bulk-fill RBCs had a depth: top hardness ratio of 0.8 and above. PMID- 27252009 TI - Antimicrobial effect of titanium dioxide after ultraviolet irradiation against periodontal pathogen. AB - We focused on the antimicrobial effects of titanium dioxide (TiO2) after stopping ultraviolet (UV) irradiation as an adjunctive treatment for peri-implantitis in this study. The aim was to determine the continuous photocatalytic effects of TiO2 after UV irradiation and its antimicrobial activity against periodontal pathogen. The continuous photocatalytic effects of TiO2 after UV irradiation were determined by electron spin resonance (ESR) spectroscopy using TiO2 particles of various sizes with various UV irradiation times. In addition, antimicrobial activity against Porphyromonas gingivalis was investigated by quantitation of colony-forming units (CFUs). The results showed that the ESR signal ratio for the UV-irradiated TiO2 was significantly higher than that of the non-irradiated TiO2. UV-irradiated TiO2 significantly reduced the number of P. gingivalis when compared with non-irradiated controls. These results suggest that TiO2 has a continuous photocatalytic effect even after stopping UV irradiation and that it showed antimicrobial activity against periodontal pathogen. PMID- 27252010 TI - Effect of new light curing units on microleakage and microhardness of resin sealants. AB - To determine new developed light curing units with shorter curing times effects on microleakage and microhardness values for resin fissure sealants. Resin filled sealant (UltraSeal-XT), resin unfilled sealant (Delton Type-II) and ormocer-based sealant (Admira-Seal) were light cured with a quartz-tungsten-halogen (QTH), two LED light and a high power LED. Two hundred and forty extracted human molars were randomly allocated into four groups according to used light-curing unit and three subgroups were formed for three different fissure sealant materials. Specimens were immersed in 0.5% basic fuchsin for 24 h, sectioned and examined under a stereomicroscope, and scored for marginal microleakage. Knoop hardness number (KHN) readings were measured after 48 h. Statistical analyses of test were found in significant difference both microleakage and microhardness values between the various light curing units. The time saving approaches in the curing light were determined higher microhardness, although it was found in higher microleakage. PMID- 27252011 TI - Influence of different composite materials and cavity preparation designs on the fracture resistance of mesio-occluso-distal inlay restoration. AB - The aim of the study to evaluate the fracture resistance of a computer-aided design/computer-aided manufacturing (CAD/CAM) and three indirect composite materials for three different mesio-occluso-distal (MOD) inlay cavity designs. A total of 120 mandibular third molar were divided into three groups: (G1) non proximal box, (G2) 2-mm proximal box, and (G3) 4-mm proximal box. Each cavity design received four composite materials: Estenia, Epricord (Kuraray, Japan), Tescera (Bisco, USA), and Cerasmart CAD/CAM blocks (GC, USA). The specimens were subjected to a compressive load at a crosshead speed of 1 mm/min. The data was analyzed using the two-way analysis of variance and Bonferroni post hoc test (p<0.05). Estenia exhibited significantly higher fracture strength than Epricord and Cerasmart in G1. In G2 and G3, there was no significant difference among the four materials. Using a non-proximal box design for the cavity can improve the fracture resistance of the inlay restoration. PMID- 27252012 TI - Prospects for the therapeutic application of sulfated polysaccharides of brown algae in diseases of the cardiovascular system: review. AB - CONTEXT: Fucoidans are water-soluble, highly sulfated, branched homo- and hetero polysaccharides derived from the fibrillar cell walls and intercellular spaces of brown seaweeds of the class Phaeophyceae. Fucoidans possess mimetic properties of the natural ligands of protein receptors and regulate functions of biological systems via key signaling molecules. OBJECTIVES: The aim of this review was to collect and combine all available scientific literature about the potential use of the fucoidans for diseases of cardiovascular system. MATERIALS AND METHODS: The review has been compiled using references from major databases such as Web of Science, PubMed, Scopus, Elsevier, Springer and Google Scholar (up to September 2015). After obtaining all reports from database (a total number is about 580), the papers were carefully analyzed in order to find data related to the topic of this review (129 references). RESULTS: An exhaustive survey of literature revealed that fucoidans possess a broad spectrum of biological activity, including anti-coagulant, hypolipidemic, anti-thrombotic, anti-inflammatory, immunomodulatory, anti-tumor, anti-adhesive and anti-hypertensive properties. Numerous investigations of fucoidans in diseases of the cardiovascular system mainly focus on pleiotropic anti-inflammatory effects. Fucoidans also possess pro angiogenic and pro-vasculogenic properties. CONCLUSION: A great number of investigations in the past years have demonstrated that fucoidans has great potential for in-depth investigation of their effects on cardiovascular system. Through this review, the authors hope to attract the attention of researchers to use fucoidan as mimetic of natural ligand receptor protein with the view of developing new formulations with an improved therapeutic value. PMID- 27252014 TI - Prediction of individual implant bone levels and the existence of implant "phenotypes". AB - OBJECTIVES: To cluster implants placed in patients of a private practice and identify possible implant "phenotypes" and predictors of individual implant mean bone levels (IIMBL). MATERIALS AND METHODS: Clinical and radiographical variables were collected from 72 implant-treated patients with 237 implants and a mean 7.4 +/- 3.5 years of function. We clustered implants using the k-means method guided by multidimensional unfolding. For predicting IIMBL, we used principal component analysis (PCA) as a variable reduction method for an ensemble selection (ES) and a support vector machines models (SVMs). Network analysis investigated variable interactions. RESULTS: We identified a cluster of implants susceptible to peri implantitis (96% of the implants in the cluster were affected by peri implantitis) and two overlapping clusters of implants resistant to peri implantitis. The cluster susceptible to peri-implantitis showed a mean IIMBL of 5.2 mm and included implants placed mainly in the lower front jaw and in mouths having a mean of eight teeth. PCA extracted the parameters such as number of teeth, full-mouth plaque scores, implant surface, periodontitis severity, age and diabetes as significant in explaining the data variability. ES and SVMs showed good results in predicting IIMBL (root-mean-squared error of 0.133 and 0.149, 10 fold cross-validation error of 0.147 and 0.150, respectively). Network analysis revealed limited interdependencies of variables among peri-implantitis-affected and non-affected implants and supported the hypothesis of the existence of distinct implant "phenotypes." CONCLUSION: Two implant "phenotypes" were identified, one with susceptibility and another with resistance to peri implantitis. Prediction of IIMBL could be achieved by using six variables. PMID- 27252015 TI - Overview of the molecular defense systems used by sea urchin embryos to cope with UV radiation. AB - The sea urchin embryo is a well-recognized developmental biology model and its use in toxicological studies has been widely appreciated. Many studies have focused on the evaluation of the effects of chemical stressors and their mixture in marine ecosystems using sea urchin embryos. These are well equipped with defense genes used to cope with chemical stressors. Recently, ultraviolet radiation (UVR), particularly UVB (280-315 nm), received more attention as a physical stressor. Mainly in the Polar Regions, but also at temperate latitudes, the penetration of UVB into the oceans increases as a consequence of the reduction of the Earth's ozone layer. In general, UVR induces oxidative stress in marine organisms affecting molecular targets such as DNA, proteins, and lipids. Depending on the UVR dose, developing sea urchin embryos show morphological perturbations affecting mainly the skeleton formation and patterning. Nevertheless, embryos are able to protect themselves against excessive UVR, using mechanisms acting at different levels: transcriptional, translational and post translational. In this review, we recommend the sea urchin embryo as a suitable model for testing physical stressors such as UVR and summarize the mechanisms adopted to deal with UVR. Moreover, we review UV-induced apoptotic events and the combined effects of UVR and other stressors. PMID- 27252013 TI - ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation. AB - The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% (13/56) of AML t(8;21) patients, including missense and truncating mutations resulting in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A. The transcription factor ZBTB7A is important for haematopoietic lineage fate decisions and for regulation of glycolysis. On a functional level, we show that ZBTB7A mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of ZBTB7A mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1/RUNX1T1 fusion. PMID- 27252016 TI - Laser-resistance sensitivity to substrate pit size of multilayer coatings. AB - Nanosecond laser-resistance to dielectric multilayer coatings on substrate pits was examined with respect to the electric-field (E-field) enhancement and mechanical properties. The laser-induced damage sensitivity to the shape of the substrate pits has not been directly investigated through experiments, thus preventing clear understanding of the damage mechanism of substrate pits. We performed a systematic and comparative study to reveal the effects of the E-field distributions and localized stress concentration on the damage behaviour of coatings on substrates with pits. To obtain reliable results, substrate pits with different geometries were fabricated using a 520-nm femtosecond laser-processing platform. By using the finite element method, the E-field distribution and localized stress of the pitted region were well simulated. The 1064-nm damage morphologies of the coated pit were directly compared with simulated E-field intensity profiles and stress distributions. To enable further understanding, a simplified geometrical model was established, and the damage mechanism was introduced. PMID- 27252017 TI - The influence of body size on the intermittent locomotion of a pelagic schooling fish. AB - There is a potential trade-off between grouping and the optimizing of the energetic efficiency of individual locomotion. Although intermittent locomotion, e.g. glide and upward swimming (GAU), can reduce the cost of locomotion at the individual level, the link between the optimization of individual intermittent locomotion and the behavioural synchronization in a group, especially among members with different sizes, is unknown. Here, we continuously monitored the schooling behaviour of a negatively buoyant fish, Pacific bluefin tuna (N = 10; 21.0 ~ 24.5 cm), for 24 h in an open-sea net cage using accelerometry. All the fish repeated GAU during the recording periods. Although the GAU synchrony was maintained at high levels (overall mean = 0.62 for the cross-correlation coefficient of the GAU timings), larger fish glided for a longer duration per glide and more frequently than smaller fish. Similar-sized pairs showed significantly higher GAU synchrony than differently sized pairs. Our accelerometry results and the simulation based on hydrodynamic theory indicated that the advantage of intermittent locomotion in energy savings may not be fully optimized for smaller animals in a group when faced with the maintenance of group cohesion, suggesting that size assortative shoaling would be advantageous. PMID- 27252018 TI - Can you teach an old parrot new tricks? Cognitive development in wild kaka (Nestor meridionalis). AB - Despite recent efforts to characterize innovative individuals within a species, we still know very little about the ontogeny of innovation ability. A number of studies have found that innovation rates are correlated with personality traits, such as neophilia and exploration. Juvenile birds are frequently more neophilic and explorative, yet few studies have found evidence of age-related differences in innovative problem-solving success. Here, we show consistently higher innovation efficiency in juveniles of a wild, omnivorous parrot species across a variety of tasks and contexts. We tested 104 kaka (Nestor meridionalis), ranging in age from four months to 13 years. Twenty-four individuals participated in all three of our problem-solving tasks, two of which involved a familiar feeder and one an entirely novel apparatus. Juveniles were the most efficient problem solvers in all three tasks. By contrast, the adults' success was context dependent and limited to the novel apparatus, which did not require modification of a pre-learned behavioural response. This suggests greater behavioural flexibility in the juvenile birds, who also showed higher persistence and exploratory diversity than adults. These traits may enable young kaka to discover efficient foraging techniques, which are then maintained throughout adulthood. PMID- 27252019 TI - Facultative asexual reproduction and genetic diversity of populations in the humivorous termite Cavitermes tuberosus. AB - Termite colonies are typically founded by a pair of sexually reproducing dispersers, which can sometimes be replaced by some of their offspring. Some Reticulitermes and Embiratermes species routinely practice asexual queen succession (AQS): the queen is replaced by neotenic daughters produced by parthenogenesis, which mate with the primary king. Here, to cast light on the evolution of AQS, we investigated another candidate species, Cavitermes tuberosus (Termitinae). Of 95 nests, 39 contained a primary queen and 28 contained neotenic females (2-667 individuals), usually with the primary king. Microsatellite analyses confirmed that colonies were initiated by single pairs after large dispersal flights. More than 80% of the neotenic females were of exclusively maternal origin and completely homozygous, suggesting automictic parthenogenesis with gamete duplication. Conversely, workers, soldiers, and most alates and primary reproductives were produced sexually. AQS often occurs late, after colonies have reached maturity, whereas early AQS in other species may boost the young colony's growth rate. We suggest additional benefits of AQS in C. tuberosus, related with a smaller size, lesser stability and higher mobility of colonies. Our data add to the phylogenetical dispersion and diversity of modalities of AQS in termites, supporting a multiple evolutionary origin of this process. PMID- 27252020 TI - Hierarchical dynamics of informational patterns and decision-making. AB - Traditional studies on the interaction of cognitive functions in healthy and disordered brains have used the analyses of the connectivity of several specialized brain networks-the functional connectome. However, emerging evidence suggests that both brain networks and functional spontaneous brain-wide network communication are intrinsically dynamic. In the light of studies investigating the cooperation between different cognitive functions, we consider here the dynamics of hierarchical networks in cognitive space. We show, using an example of behavioural decision-making based on sequential episodic memory, how the description of metastable pattern dynamics underlying basic cognitive processes helps to understand and predict complex processes like sequential episodic memory recall and competition among decision strategies. The mathematical images of the discussed phenomena in the phase space of the corresponding cognitive model are hierarchical heteroclinic networks. One of the most important features of such networks is the robustness of their dynamics. Different kinds of instabilities of these dynamics can be related to 'dynamical signatures' of creativity and different psychiatric disorders. The suggested approach can also be useful for the understanding of the dynamical processes that are the basis of consciousness. PMID- 27252021 TI - Active dispersal in loggerhead sea turtles (Caretta caretta) during the 'lost years'. AB - Highly migratory marine species can travel long distances and across entire ocean basins to reach foraging and breeding grounds, yet gaps persist in our knowledge of oceanic dispersal and habitat use. This is especially true for sea turtles, whose complex life history and lengthy pelagic stage present unique conservation challenges. Few studies have explored how these young at-sea turtles navigate their environment, but advancements in satellite technology and numerical models have shown that active and passive movements are used in relation to open ocean features. Here, we provide the first study, to the best of our knowledge, to simultaneously combine a high-resolution physical forcing ocean circulation model with long-term multi-year tracking data of young, trans-oceanic North Pacific loggerhead sea turtles during their 'lost years' at sea. From 2010 to 2014, we compare simulated trajectories of passive transport with empirical data of 1-3 year old turtles released off Japan (29.7-37.5 straight carapace length cm). After several years, the at-sea distribution of simulated current-driven trajectories significantly differed from that of the observed turtle tracks. These results underscore current theories on active dispersal by young oceanic stage sea turtles and give further weight to hypotheses of juvenile foraging strategies for this species. Such information can also provide critical geographical information for spatially explicit conservation approaches to this endangered population. PMID- 27252022 TI - Invasion of two tick-borne diseases across New England: harnessing human surveillance data to capture underlying ecological invasion processes. AB - Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach-occupancy modelling to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct invasion trajectories of the co-vectored pathogens remain unresolved. Our approach allowed us to estimate the unobserved ecological processes underlying pathogen spread while accounting for imperfect detection of human cases. Our model predicts that tick-borne diseases spread in a diffusion-like manner with occasional long-distance dispersal and that babesiosis spread exhibits strong dependence on Lyme disease. PMID- 27252024 TI - Design, synthesis and biological evaluation of a novel series of glycosylated platinum(iv) complexes as antitumor agents. AB - A new series of glycosylated Pt(iv) complexes were designed, synthesized and evaluated for antitumor activities in vitro and in vivo. The incorporation of glycosyl groups to the Pt(iv) system has much influence on the antitumor abilities. Four lead compounds with activities comparable or even superior to cisplatin and oxaliplatin are screened out. These Pt(iv) complexes could be reduced to release Pt(ii) complexes and cause the death of tumour cells. The apoptosis-inducing properties of these compounds are similar to cisplatin. The accumulation of the glycosylated Pt(iv) complexes in cells and DNA is higher than cisplatin and oxaliplatin. The in vivo assay demonstrates that the tested compounds inhibit the growth of HepG2 tumors with low toxicity. PMID- 27252023 TI - Transmission and pathogenicity of novel reassortants derived from Eurasian avian like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs. AB - Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models. PMID- 27252025 TI - Antimicrobial photodynamic therapy of S. mutans biofilms attached to relevant dental materials. AB - BACKGROUND: Antimicrobial Photodynamic therapy (aPDT) has demonstrated efficacy in situations where conventional antibiotic therapies can be challenged such as biofilms, gram-negative bacteria, and antimicrobial resistant organisms. Surface characteristics can affect biofilm adherence and integrity and so may modify the effectiveness of aPDT. This study investigates the killing efficacy of aPDT on S. mutans biofilms grown on relevant dental substrata, examining the killing efficacy and specifically the effects of aPDT on the biofilm matrix architecture. MATERIALS AND METHODS: S. mutans (NCTC 10449) was grown in 48 hours biofilms on different substrata, specifically glass, titanium, and denture acrylic. During aPDT assays, the biofilms were treated with a purpurin based sensitizer ([25 ug/ml] in DMSO) for 30 minutes, then exposed to a 664 nm diode laser at light doses of 15, 30, and 45 J/cm2 . Colony forming unit assays were performed to determine survival following treatment. Controls for comparison in survival assays consisted of (No light/No PS; No light/PS; and No light/DMSO). MAIR-IR spectroscopy analysis was performed to investigate aPDT effects on biofilm composition before and after jet impingement. RESULTS: Survival was greatly reduced in the biofilm cultures following the aPDT assays. All light doses achieved a greater then 3-log inactivation on 48 hours biofilms grown on polished denture acrylic. The higher light doses (45 and 30 J) achieved greater than 3-log inactivation in 48 hours biofilms grown on glass. The higher light doses (30 and 45 J/cm2 ) produced a 2-log inactivation in 48 hours biofilms grown on titanium. Multiple attenuated internal reflection infrared (MAIR-IR) spectroscopy data demonstrates enhanced loss of exopolysaccharide (EPS) and Amide in the aPDT treated biofilms following jet impingement. CONCLUSION: Antimicrobial PDT experiments using a purpurin based sensitizer and laser light doses of 15, 30, and 45 J/cm2 , against S. mutans biofilm grown on different surfaces, show the effectiveness of this therapy. In CFU survival assays, a dose response to the laser is evident. While considerable disinfection was achieved on all surfaces compared to the controls, not all surfaces could be disinfected equally. MAIR-IR spectroscopy showed that aPDT groups lost more EPS and Amide versus controls, suggesting aPDT induced biofilm embrittlement, which was revealed by jet impingement. With demonstrated efficacy against various microbes and on different substrata, antimicrobial aPDT shows potential for clinical application in biofilm mediated diseases such as peri-implantitis and periodontitis. Lasers Surg. Med. 48:995-1005, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27252026 TI - Ac-LPFFD-Th: A Trehalose-Conjugated Peptidomimetic as a Strong Suppressor of Amyloid-beta Oligomer Formation and Cytotoxicity. AB - The inhibition of amyloid formation is a promising therapeutic approach for the treatment of neurodegenerative diseases. Peptide-based inhibitors, which have been widely investigated, are generally derived from original amyloid sequences. Most interestingly, trehalose, a nonreducing disaccharide of alpha-glucose, is effective in preventing the aggregation of numerous proteins. We have determined that the development of hybrid compounds could provide new molecules with improved properties that might synergically increase the potency of their single moieties. In this work, the ability of Ac-LPFFD-Th, a C-terminally trehalose conjugated derivative, to slow down the Abeta aggregation process was investigated by means of different biophysical techniques, including thioflavin T fluorescence, dynamic light scattering, ESI-MS, and NMR spectroscopy. Moreover, we demonstrate that Ac-LPFFD-Th modifies the aggregation features of Abeta and protects neurons from Abeta oligomers' toxic insult. PMID- 27252027 TI - Ketamine alone or combined with midazolam or dexmedetomidine does not affect anxiety-like behaviours and memory in adult Wistar rats. AB - Ketamine administration has been associated with controversial behavioural impairments and psychotic episodes. Even though ketamine alone and in combination with midazolam or dexmedetomidine are frequently used in laboratory animals, the side-effects of such protocols are not well known. Therefore, our aim was to evaluate the effects of ketamine alone and in combination with midazolam or dexmedetomidine on emotional reactivity, as well as the effects on learning and memory in adult rats at least 48 h after anaesthesia. The evaluation of the potential influence of 100 mg/kg ketamine administered alone and in combination with midazolam (5 mg/kg), or dexmedetomidine (0.25 mg/kg) on spatial learning and recognition memory was studied in adult Wistar rats using the radial maze as well as object recognition and location tests. The influence of these combinations on emotional reactivity was investigated using the new exploration test and the elevated plus maze. Results showed that ketamine alone or in combination with midazolam or dexmedetomidine affected neither spatial and recognition memory, nor emotional reactivity. These results reinforce the safe clinical use of ketamine and its combinations in rats in a research context since the administration of these anaesthetic combinations did not produce significant changes with regard to spatial and recognition memory or emotional reactivity. Furthermore, these results indicate that the quality of scientific data produced in adult rat neurobehavioural research is not jeopardized by the use of these anaesthetic protocols. PMID- 27252028 TI - The stripe rust fungal effector PEC6 suppresses pattern-triggered immunity in a host species-independent manner and interacts with adenosine kinases. AB - We identified a wheat stripe rust (Puccinia striiformis) effector candidate (PEC6) with pattern-triggered immunity (PTI) suppression function and its corresponding host target. PEC6 compromised PTI host species-independently. In Nicotiana benthamiana, it hampers reactive oxygen species (ROS) accumulation and callose deposition induced by Pseudomonas fluorescens. In Arabidopsis, plants expressing PEC6 were more susceptible to Pseudomonas syringae pv. tomato (Pto) DC3000 DeltaAvrPto/DeltaAvrPtoB. In wheat, PEC6-suppression of P. fluorescens elicited PTI was revealed by the fact that it allowed activation of effector triggered immunity by Pto DC3000. Knocking down of PEC6 expression by virus mediated host-induced gene silencing decreased the number of rust pustules, uncovering PEC6 as an important pathogenicity factor. PEC6, overexpressed in plant cells without its signal peptide, was localized to the nucleus and cytoplasm. A yeast two-hybrid assay showed that PEC6 interacts with both wheat and Arabidopsis adenosine kinases (ADKs). Knocking down wheat ADK expression by virus-induced gene silencing reduced leaf growth and enhanced the number of rust pustules, indicating that ADK is important in plant development and defence. ADK plays essential roles in regulating metabolism, cytokinin interconversion and methyl transfer reactions, and our data propose a model where PEC6 may affect one of these processes by targeting ADK to favour fungal growth. PMID- 27252029 TI - High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka - implications for global suicide prevention. AB - BACKGROUND: Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. METHODS: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. FINDINGS: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. CONCLUSIONS: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452 1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates. PMID- 27252030 TI - Development of infant and toddler sleep patterns: real-world data from a mobile application. AB - The aim of this study was to investigate the development of infant and toddler sleep patterns. Data were collected on 841 children (aged from birth to 36 months) via a free, publicly available, commercially sponsored iPhone app. Analyses were conducted on caregiver recordings of 156 989 sleep sessions across a 19-month period. Detailed visualizations of the development of sleep across the first 3 years of life are presented. In the first 3 months, sleep sessions primarily lasted less than 3.5 h throughout the day. Between 3 and 7 months old, sleep consolidated into two naps of about 1.5 h in length and a night-time sleep session of about 10.5 h. Across age groups, a negative relationship was observed between the start of bedtime and the length of the night-time sleep session (i.e. later bedtime is associated with a shorter night-time sleep period). The length of daytime sleep sessions (naps) varied with age, decreasing between 1 and 5 months old, and then increasing monotonically through 28 months. Morning wake time was observed to be invariant in children aged 5-36 months. Sleep patterns are ever-changing across the first few years with wide individual variability. Sleep patterns start to develop more clearly at 5-6 months, when longer night time sleep duration begins and sleep consolidation occurs. Daytime sleep patterns appeared to become more consistent and consolidated later in age than night-time sleep. Finally, there is greater variability in bedtimes than wake times, with bedtimes having a greater influence on night-time sleep duration. PMID- 27252031 TI - Myxoid cutaneous tumors: a review. AB - Unified by the common finding of myxoid background, the group of myxoid cutaneous tumors comprises many entities with different lineages, immunohistochemical profiles, underlying genetic abnormalities and biologic behaviors. These tumors may have significant histopathologic overlap causing diagnostic difficulty. Careful attention to subtle histopathologic features is key to accurate diagnosis. Immunohistochemical stains and molecular tests are valuable in selected cases. This review discusses selected myxoid tumors and myxoid variants of cutaneous tumors and focuses on key pathologic features and an effective strategy for the use of ancillary tests. PMID- 27252032 TI - The psychosocial experiences of breast cancer amongst Black, South Asian and White survivors: do differences exist between ethnic groups? AB - BACKGROUND: Very little UK-based research has examined breast cancer-related experiences of Black and Minority Ethnic populations, and we do not know whether the psychosocial impact of diagnosis and treatment in this group is any different to that of White women. Therefore, this study examined similarities and differences amongst Black, South Asian and White breast cancer survivors. METHODS: A quantitative, cross-sectional survey was conducted; 173 breast cancer survivors (80 White, 53 South Asian and 40 Black) completed a questionnaire, which assessed psychological functioning, social support, body image and beliefs about cancer. RESULTS: Significant differences (p < 0.05) were reported between White and South Asian participants: compared with White women, South Asian participants reported higher levels of anxiety and depression, poorer quality of life and held higher levels of internal and fatalistic beliefs pertaining to cancer. Black and South Asian women reported higher levels of body image concerns than White women, and held stronger beliefs that God was in control of their cancer. South Asian women turned to religion as a source of support more than Black and White women. CONCLUSION: This study enhances current understanding of the experience and impact of breast cancer amongst Black and South Asian women, and demonstrates similarities and differences between the ethnic groups. The findings highlight implications for healthcare professionals, particularly in relation to providing culturally sensitive care and support to their patients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27252033 TI - Shared structuring resources across domains: double task effects from linguistic processing on the structural integration of pitch sequences. AB - Many studies have reported evidence suggesting that resources involved in linguistic structural processing might be domain-general by demonstrating interference from simultaneously presented non-linguistic stimuli on the processing of sentences (Slevc, Rosenberg, & Patel, 2009 ). However, the complexity of the analysed linguistic processes often precludes the interpretation of such interference as being based on structural-rather than more general-processing resources (Perruchet & Poulin-Charronnat, 2013 ). We therefore used linguistic structure as a source of interference for another structural processing task, by asking participants to read sentences while processing experimentally manipulated pitch sequences. Half of the sentences contained a segment with either an "out-of-context" sentential violation or a "garden path" unexpectancy. Furthermore, the pitch sequences contained a cluster shift, which did or did not align with the sentential unexpectancies. A two-tone recognition task followed each pitch sequence, providing an index of the strength with which this structural boundary was processed. When a "garden path" unexpectancy (requiring structural reintegration) accompanied the cluster shift, the structural boundary induced by this shift was processed more shallowly. No such effect occurred with non-reintegratable "out-of-context" sentential violations. Furthermore, the discussed interference effect can be isolated from general pitch recognition performance, supporting the interpretation of such interference as being based on overlapping structural processing resources (Kljajevic, 2010 ; Patel, 2003 ). PMID- 27252034 TI - Down Syndrome: Changing Cardiac Phenotype? PMID- 27252035 TI - Trends in Congenital Heart Defects in Infants With Down Syndrome. AB - BACKGROUND: As a result of antenatal screening, abortion of fetuses with Down syndrome has become increasingly common. Little is known about the cardiovascular phenotype in infants with Down syndrome born today. METHODS: Population-based cohort study based on national health registers including 2588 infants with Down syndrome, live-born in Sweden from 1992 to 2012. Risk ratios for congenital heart defects were calculated per 3-year period, adjusted for maternal age, parity, BMI, smoking, diabetes and hypertensive disease, and infant gender. RESULTS: Any congenital heart defect was diagnosed in 54% of infants with Down syndrome. Overall, year of birth was not associated with risk of any congenital heart defect. However, the risk of complex congenital heart defects decreased over time. Compared with 1992 to 1994, the risk in 2010 to 2012 was reduced by almost 40% (adjusted risk ratio 0.62, 95% confidence interval 0.48-0.79). In contrast, risks for isolated ventricular septal defect (VSD) or atrial septal defect showed significant increases during latter years. Overall, the 3 most common diagnoses were atrioventricular septal defect, VSD, or atrial septal defect, accounting for 42%, 22%, and 16% of congenital heart defects, respectively. Although atrioventricular septal defect was far more common than VSD in 1992 to 1994, they were equally common in 2010 to 2012. CONCLUSIONS: Complex congenital heart defects have become less common in infants diagnosed with Down syndrome. This phenotypic shift could be a result of selective abortion of fetuses with Down syndrome, or due to general improvements in antenatal diagnostics of complex congenital heart defects. PMID- 27252036 TI - A 10-Month-Old With Intermittent Hypotonia and Paralysis. AB - A 10-month-old boy presented with a 1-day history of flaccid quadriplegia and dysconjugate gaze. His history was remarkable for stereotyped episodes of flaccid quadriplegia or hemiplegia, oculomotor abnormalities, and limb or neck posturing, beginning in the first days of life and becoming more frequent and more prolonged over time. The patient was healthy and developmentally normal between episodes. Results of extensive laboratory evaluations, including EEG and brain imaging studies, were negative. The patient's history, diagnostic evaluation, and final diagnosis are reviewed. This case illustrates the importance of a fundamental understanding of neurologic localization in pediatric care and a focused diagnostic approach to an infant with paroxysmal neurologic signs. PMID- 27252038 TI - Freud and the human connectome. PMID- 27252037 TI - Uncovering phonological and orthographic selectivity across the reading network using fMRI-RA. AB - Reading has been shown to rely on a dorsal brain circuit involving the temporoparietal cortex (TPC) for grapheme-to-phoneme conversion of novel words (Pugh et al., 2001), and a ventral stream involving left occipitotemporal cortex (OTC) (in particular in the so-called "visual word form area", VWFA) for visual identification of familiar words. In addition, portions of the inferior frontal cortex (IFC) have been posited to be an output of the dorsal reading pathway involved in phonology. While this dorsal versus ventral dichotomy for phonological and orthographic processing of words is widely accepted, it is not known if these brain areas are actually strictly sensitive to orthographic or phonological information. Using an fMRI rapid adaptation technique we probed the selectivity of the TPC, OTC, and IFC to orthographic and phonological features during single word reading. We found in two independent experiments using different task conditions in adult normal readers, that the TPC is exclusively sensitive to phonology and the VWFA in the OTC is exclusively sensitive to orthography. The dorsal IFC (BA 44), however, showed orthographic but not phonological selectivity. These results support the theory that reading involves a specific phonological-based temporoparietal region and a specific orthographic based ventral occipitotemporal region. The dorsal IFC, however, was not sensitive to phonological processing, suggesting a more complex role for this region. PMID- 27252039 TI - Ca2+ Signaling and Cell Death Induced by Protriptyline in HepG2 Human Hepatoma Cells. AB - The effect of protriptyline on Ca2+ physiology in human hepatoma is unclear. This study explored the effect of protriptyline on [Ca2+ ]i and cytotoxicity in HepG2 human hepatoma cells. Protriptyline (50-150 MUM) evoked [Ca2+ ]i rises. The Ca2+ entry was inhibited by removal of Ca2+ . Protriptyline-induced Ca2+ entry was confirmed by Mn2+ -induced quench of fura-2 fluorescence. Except nifedipine, econazole, SKF96365, GF109203X, and phorbol 12-myristate 13 acetate did not inhibit Ca2+ entry. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) inhibited 40% of protriptyline-induced response. Treatment with protriptyline abolished BHQ-induced response. Inhibition of phospholipase C (PLC) suppressed protriptyline-evoked response by 70%. At 20 40 MUM, protriptyline killed cells which was not reversed by the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in HepG2 cells, protriptyline induced [Ca2+ ]i rises that involved Ca2+ entry through nifedipine-sensitive Ca2+ channels and PLC-dependent Ca2+ release from endoplasmic reticulum. Protriptyline induced Ca2+ -independent cell death. PMID- 27252040 TI - The efficacy of lenalidomide combination therapy in heavily pretreated non Hodgkin lymphoma patients: an Italian observational, multicenter, retrospective study. PMID- 27252041 TI - Elevated CO2 and temperature increase soil C losses from a soybean-maize ecosystem. AB - Warming temperatures and increasing CO2 are likely to have large effects on the amount of carbon stored in soil, but predictions of these effects are poorly constrained. We elevated temperature (canopy: +2.8 degrees C; soil growing season: +1.8 degrees C; soil fallow: +2.3 degrees C) for 3 years within the 9th 11th years of an elevated CO2 (+200 ppm) experiment on a maize-soybean agroecosystem, measured respiration by roots and soil microbes, and then used a process-based ecosystem model (DayCent) to simulate the decadal effects of warming and CO2 enrichment on soil C. Both heating and elevated CO2 increased respiration from soil microbes by ~20%, but heating reduced respiration from roots and rhizosphere by ~25%. The effects were additive, with no heat * CO2 interactions. Particulate organic matter and total soil C declined over time in all treatments and were lower in elevated CO2 plots than in ambient plots, but did not differ between heat treatments. We speculate that these declines indicate a priming effect, with increased C inputs under elevated CO2 fueling a loss of old soil carbon. Model simulations of heated plots agreed with our observations and predicted loss of ~15% of soil organic C after 100 years of heating, but simulations of elevated CO2 failed to predict the observed C losses and instead predicted a ~4% gain in soil organic C under any heating conditions. Despite model uncertainty, our empirical results suggest that combined, elevated CO2 and temperature will lead to long-term declines in the amount of carbon stored in agricultural soils. PMID- 27252042 TI - Large spin-filtering effect in Ti-doped defective zigzag graphene nanoribbon. AB - Through first-principles calculations using the nonequilibrium Green's function formalism together with density functional theory, we study the conductance of double-vacancy zigzag graphene nanoribbons doped with four transition metal atoms Ti, V, Cr and Fe. We show that Ti doping induces large spin-filtering with an efficiency in excess of 90% for bias voltages below 0.5 V, while the other metal adatoms do not induce large spin filtering. This is despite the fact that the Ti dopant possesses small spin moment, while large moments reside on V, Cr and Fe dopants. Our analysis shows that the suppression of transmission in the spin-down channel in the Ti-doped graphene nanoribbon, thus the large spin filtering efficiency, is due to transmission anti-resonance arising from destructive quantum interference. These findings suggest that the decoration of graphene with titanium, and possibly other transition metals, can act as effective spin filters for nanospintronic applications. PMID- 27252044 TI - Review of anthraquinone applications for pest management and agricultural crop protection. AB - We have reviewed published anthraquinone applications for international pest management and agricultural crop protection from 1943 to 2016. Anthraquinone (AQ) is commonly found in dyes, pigments and many plants and organisms. Avian repellent research with AQ began in the 1940s. In the context of pest management, AQ is currently used as a chemical repellent, perch deterrent, insecticide and feeding deterrent in many wild birds, and in some mammals, insects and fishes. Criteria for evaluation of effective chemical repellents include efficacy, potential for wildlife hazards, phytotoxicity and environmental persistence. As a biopesticide, AQ often meets these criteria of efficacy for the non-lethal management of agricultural depredation caused by wildlife. We summarize published applications of AQ for the protection of newly planted and maturing crops from pest birds. Conventional applications of AQ-based repellents include preplant seed treatments [e.g. corn (Zea mays L.), rice (Oryza sativa L.), sunflower (Helianthus annuus L.), wheat (Triticum spp.), millet (Panicum spp.), sorghum (Sorghum bicolor L.), pelletized feed and forest tree species] and foliar applications for rice, sunflower, lettuce (Lactuca sativa L.), turf, sugar beets (Beta vulgaris L.), soybean (Glycine max L.), sweet corn and nursery, fruit and nut crops. In addition to agricultural repellent applications, AQ has also been used to treat toxicants for the protection of non-target birds. Few studies have demonstrated AQ repellency in mammals, including wild boar (Sus scrofa, L.), thirteen-lined ground squirrels (Ictidomys tridecemlineatus, Mitchill), black tailed prairie dogs (Cyomys ludovicainus, Ord.), common voles (Microtus arvalis, Pallas), house mice (Mus musculus, L.), Tristram's jirds (Meriones tristrami, Thomas) and black rats (Rattus rattus L.). Natural sources of AQ and its derivatives have also been identified as insecticides and insect repellents. As a natural or synthetic biopesticide, AQ is a promising candidate for many contexts of non-lethal and insecticidal pest management. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27252043 TI - A Schisandra-Derived Compound Schizandronic Acid Inhibits Entry of Pan-HCV Genotypes into Human Hepatocytes. AB - Despite recent progress in the development of hepatitis C virus (HCV) inhibitors, cost-effective antiviral drugs, especially among the patients receiving liver transplantations, are still awaited. Schisandra is a traditional medicinal herb used to treat a range of liver disorders including hepatitis for thousands of years in China. To isolate the bioactive compounds of schisandra for the treatment of HCV infection, we screened a schisandra-extracts library and identified a tetracyclic triterpenoid, schizandronic acid (SZA), as a novel HCV entry inhibitor. Our findings suggested that SZA potently inhibited pan-HCV genotype entry into hepatoma cells and primary human hepatocytes without interfering virus binding on cell surface or internalization. However, virion cell fusion process was impaired in the presence of SZA, along with the increased host membrane fluidity. We also found that SZA inhibited the spread of HCV to the neighboring cells, and combinations of SZA with interferon or telaprevir resulted in additive synergistic effect against HCV. Additionally, SZA diminished the establishment of HCV infection in vivo. The SZA target is different from conventional direct-acting antiviral agents, therefore, SZA is a potential therapeutic compound for the development of effective HCV entry inhibitors, especially for patients who need to prevent HCV reinfection during the course of liver transplantations. PMID- 27252045 TI - Four decades without diagnosis: Sheehan's syndrome, a retrospective analysis. AB - AIM: Sheehan's syndrome (SS) remains a frequent cause of hypopituitarism in undeveloped and developing countries, but due to improvements in obstetric care, it is rare in developed countries. We aimed to share the results of a retrospective study analyzing the demographic, clinical, imaging, and hormonal characteristics of a large group of patients with SS, and also increase awareness of this syndrome especially in developed countries. METHODS: The medical records of 124 patients with SS patients who were followed up in the Endocrinology Department of Dicle University between 1995 and 2015 were assessed retrospectively. RESULTS: The mean period of diagnostic delay was 20.37 +/- 8.34 years on average. 5.7% of patients with SS were literate; 62% of patients delivered at home. Anemia was identified in 64.5% of SS patients. Mean blood sodium levels were 129.8 +/- 11.3 mEq/L. The mean urine densities were 1013 +/- 6.5. Osteoporosis and osteopenia were found in 44 (35.4%) and 71 (57.2%) patients, respectively, According to pituitary magnetic resonance imaging (MRI) analyses, 92 (74.2%) patients with SS had completely empty sella, 29 (23.3%) had partially empty sella, and 1 patient had microadenoma, and 2 had normal pituitary MRI results. CONCLUSIONS: Improved obstetric care and effective interventions for postpartum hemorrhage have limited the prevalence of SS in developed countries. However, in developing countries like Turkey, SS due to postpartum bleeding remains common. Thus, physician's awareness of the symptoms of SS is urgently required to avoid the associated morbidity and mortality. PMID- 27252048 TI - Tri-layer wrinkling as a mechanism for anchoring center initiation in the developing cerebellum. AB - During cerebellar development, anchoring centers form at the base of each fissure and remain fixed in place while the rest of the cerebellum grows outward. Cerebellar foliation has been extensively studied; yet, the mechanisms that control anchoring center initiation and position remain insufficiently understood. Here we show that a tri-layer model can predict surface wrinkling as a potential mechanism to explain anchoring center initiation and position. Motivated by the cerebellar microstructure, we model the developing cerebellum as a tri-layer system with an external molecular layer and an internal granular layer of similar stiffness and a significantly softer intermediate Purkinje cell layer. Including a weak intermediate layer proves key to predicting surface morphogenesis, even at low stiffness contrasts between the top and bottom layers. The proposed tri-layer model provides insight into the hierarchical formation of anchoring centers and establishes an essential missing link between gene expression and evolution of shape. PMID- 27252046 TI - Absolute protein quantification of the yeast chaperome under conditions of heat shock. AB - Chaperones are fundamental to regulating the heat shock response, mediating protein recovery from thermal-induced misfolding and aggregation. Using the QconCAT strategy and selected reaction monitoring (SRM) for absolute protein quantification, we have determined copy per cell values for 49 key chaperones in Saccharomyces cerevisiae under conditions of normal growth and heat shock. This work extends a previous chemostat quantification study by including up to five Q peptides per protein to improve confidence in protein quantification. In contrast to the global proteome profile of S. cerevisiae in response to heat shock, which remains largely unchanged as determined by label-free quantification, many of the chaperones are upregulated with an average two-fold increase in protein abundance. Interestingly, eight of the significantly upregulated chaperones are direct gene targets of heat shock transcription factor-1. By performing absolute quantification of chaperones under heat stress for the first time, we were able to evaluate the individual protein-level response. Furthermore, this SRM data was used to calibrate label-free quantification values for the proteome in absolute terms, thus improving relative quantification between the two conditions. This study significantly enhances the largely transcriptomic data available in the field and illustrates a more nuanced response at the protein level. PMID- 27252047 TI - Eyes wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state dependent manner. AB - Transcranial alternating current stimulation (tACS) is used to modulate brain oscillations to measure changes in cognitive function. It is only since recently that brain activity in human subjects during tACS can be investigated. The present study aims to investigate the phase relationship between the external tACS signal and concurrent brain activity. Subjects were stimulated with tACS at individual alpha frequency during eyes open and eyes closed resting states. Electrodes were placed at Cz and Oz, which should affect parieto-occipital areas most strongly. Source space magnetoencephalography (MEG) data were used to estimate phase coherence between tACS and brain activity. Phase coherence was significantly increased in areas in the occipital pole in eyes open resting state only. The lag between tACS and brain responses showed considerable inter individual variability. In conclusion, tACS at individual alpha frequency entrains brain activity in visual cortices. Interestingly, this effect is state dependent and is clearly observed with eyes open but only to a lesser extent with eyes closed. PMID- 27252049 TI - The genetics of speciation: Insights from Fisher's geometric model. AB - Research in speciation genetics has uncovered many robust patterns in intrinsic reproductive isolation, and fitness landscape models have been useful in interpreting these patterns. Here, we examine fitness landscapes based on Fisher's geometric model. Such landscapes are analogous to models of optimizing selection acting on quantitative traits, and have been widely used to study adaptation and the distribution of mutational effects. We show that, with a few modifications, Fisher's model can generate all of the major findings of introgression studies (including "speciation genes" with strong deleterious effects, complex epistasis and asymmetry), and the major patterns in overall hybrid fitnesses (including Haldane's Rule, the speciation clock, heterosis, hybrid breakdown, and male-female asymmetry in the F1). We compare our approach to alternative modeling frameworks that assign fitnesses to genotypes by identifying combinations of incompatible alleles. In some cases, the predictions are importantly different. For example, Fisher's model can explain conflicting empirical results about the rate at which incompatibilities accumulate with genetic divergence. In other cases, the predictions are identical. For example, the quality of reproductive isolation is little affected by the manner in which populations diverge. PMID- 27252051 TI - School Pharmacists and Methods of Analysis in Health Science: Pharmaceutical Health Science for the Protection of Children's Health. PMID- 27252050 TI - Fluorescently Sensing of DNA Triplex Assembly Using an Isoquinoline Alkaloid as Selector, Stabilizer, Inducer, and Switch-On Emitter. AB - DNA triplex assembly has attracted a variety of interest in the regulation of genetic expression, drug screening, molecular switches, and sensors. However, these achievements are essentially dependent on the formation and stability of the triplex assembly. Herein, the recognition of DNA triplex assembly with various isoquinoline alkaloids was investigated. We found that natural chelerythrine (CHE) exhibits the highest selectivity in recognizing the triplex structure. The DNA triplex stability is substantially increased upon CHE binding, as opposed to the invariance in the stability of the duplex counterpart. CHE also favors the assembly of the triplex-forming oligonucleotide (TFO) with its duplex counterpart. The triplex binding switches CHE to a strong fluorescent emitter, which suggests CHE as a useful probe in following triplex assembly. As a unique triplex selector, inducer, and emitter, CHE successfully reports the wide pH- and metal-ion-dependent tunability of the triplex nanoswitch in a label-free manner. PMID- 27252052 TI - Management for School Environmental Health in Japan. AB - Some acts such as the Basic Environment Act are aimed at managing environmental health for a productive living environment in Japan. School is not only a place where lessons for a better future are taught but also an environment in which children spend many hours of their day. Therefore, activities involving regular checks are important to maintain and improve the school environment. Article 5 of the School Health and Safety Act states that schools must make plans and carry out regular checks on school environmental health. Article 6 prescribes that the Minister of Education, Culture, Sports, Science and Technology establish a "school environmental health standard". This standard involves metrics on the classroom environment (quality of air, illumination, and noise levels), quality of drinking/pool water and so on, and their standard values and evaluation methods. Article 23 prescribes that each school except colleges/universities have a school pharmacist. The school pharmacist plays an important role in maintaining and improving the school's environmental health. However, the current actions taken are not adequate. Therefore, prospects for future activities will be discussed based on the current situations and problems. PMID- 27252053 TI - School Pharmacist/School Environmental Hygienic Activities at School Site. AB - The "School Health and Safety Act" was enforced in April 2009 in Japan, and "school environmental health standards" were established by the Minister of Education, Culture, Sports, Science and Technology. In Article 24 of the Enforcement Regulations, the duties of the school pharmacist have been clarified; school pharmacists have charged with promoting health activities in schools and carrying out complete and regular checks based on the "school environmental health standards" in order to protect the health of students and staff. In supported of this, the school pharmacist group of Japan Pharmaceutical Association has created and distributed digital video discs (DVDs) on "check methods of school environmental health standards" as support material. We use the DVD to ensure the basic issues that school pharmacists deal with, such as objectives, criteria, and methods for each item to be checked, advice, and post measures. We conduct various workshops and classes, and set up Q&A committees so that inquiries from members are answered with the help of such activities. In addition, school pharmacists try to improve the knowledge of the school staff on environmental hygiene during their in-service training. They also conduct "drug abuse prevention classes" at school and seek to improve knowledge and recognition of drugs, including "dangerous drugs". PMID- 27252054 TI - School Pharmacist and "Methods of Analysis in Health Science". AB - The major duty of a school pharmacist is to serve as an expert in analysis. School pharmacists must perform regular and thorough assessments based on school environmental health standards. The objectives of the "environmental" component of the pharmacy education model core curriculum include performing analyses corresponding to the regularly checked items of the school environmental health standards. Students of the School of Pharmacy should cultivate their expertise in environmental analysis and environmental health, through practices such as sample collection, analysis operation, and evaluation of test results. As analysis experts, school pharmacists must know the principles and characteristics of analytical methods. The "Methods of Analysis in Health Science" published by the Pharmaceutical Society of Japan, provides comprehensive information on regular items to be cheked in the school environmental health standards, and school pharmacists should use this as a guide in their activities. PMID- 27252055 TI - Current Indoor Air Quality in Japan. AB - People spend more than two thirds of their daily time indoors. Hence, maintaining a healthy indoor environment is indispensable for the prevention of building related illness. In Japan, guidelines for indoor air quality have been established for 13 volatile/semi-volatile organic compounds (VOCs/SVOCs). These guidelines are now under revision by the Committee on Sick House Syndrome: Indoor Air Pollution. In order to gain information on the current indoor air pollutants and their levels, we carried out a nation-wide survey of VOCs and aldehydes in indoor residential air during 2012-2013. In this review, I concisely summarized the current indoor air quality of Japan. PMID- 27252056 TI - Exposure Measurements in Japan Environment and Children's Study. AB - The Japan Ministry of the Environment is conducting a large-scale birth cohort study called the Japan Environment and Children's Study (JECS), which involves 100000 mother-child pairs. Mothers are enrolled during pregnancy, and their children are followed up and studied until they reach the age of 13 years. The JECS started recruiting mothers in January 2011 and completed the registration of more than 103000 mothers in March 2014. The National Institute for Environmental Studies takes the lead in the study programming and implementation in cooperation with the National Centre for Child Health and Development and 15 Regional Centres that reach out to the study participants. In the study, the effects of environmental factors on children's health and development are investigated. The environment in this study is defined not only as air, soil, water, and indoor environments but also as various chemical substances, physical conditions, socioeconomic factors, psychological conditions, lifestyles and community situations. Mothers' and children's exposures to these environmental factors are measured through chemical analyses of biospecimens collected during pregnancy and after birth, questionnaires and computer modelling. The homes of the randomly selected participants (5000) are visited to measure the concentrations of volatile organic compounds, nitrogen and sulphuric oxides and particulate matter. Vacuum dust samples are also collected for chemical analysis. All these data will be combined with the information collected by the dwelling unit observation to assess the exposure of children aged 1.5 and 3 years. PMID- 27252057 TI - Mechanisms and Pharmacological Strategy Targeting Dysfunction of Endoplasmic Reticulum. PMID- 27252058 TI - Regulation of Unfolded Protein Response via Protein S-nitrosylation. AB - Nitric oxide (NO) plays a pivotal function in neurotransmission, vasodilation, proliferation, and apoptosis in various types of cells via protein S nitrosylation. Previously we demonstrated that protein disulfide isomerase (PDI) is S-nitrosylated in brains manifesting sporadic neurodegenerative diseases. This modification results in dysfunction of its enzymatic activity and consequently the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER). The aim of this study was to clarify the detailed function of NO on unfolded protein response (UPR) branches. We here found that the ER stress sensor IRE1alpha is S-nitrosylated. Interestingly, NO specifically abrogates ribonuclease activity, but not oligomerization or autophosphorylation of IRE1alpha. Site-directed mutagenesis revealed that Cys 931 and Cys951 in IRE1 are targets for S-nitrosylation. These mutants expressing in IRE1alpha knockout MEF showed a resistant role to the inhibition of nuclease activity by NO. Thus, we elucidated the effects of S-nitrosylation on ER stress sensors that mediate the UPR, and thus contribute to cell death pathways. PMID- 27252059 TI - Physiological Roles of Ubiquitin Ligases Related to the Endoplasmic Reticulum. AB - Studies on endoplasmic reticulum (ER)-associated degradation (ERAD), in which unfolded proteins accumulated in the ER are selectively transported to the cytosol for degradation by the ubiquitin-proteasome system, have been focused on molecular mechanisms in yeast. In human, disruption of the ER quality control system causes various diseases, such as neurodegenerative disease, lifestyle disease, and cancer. However, there are many ERAD genes with unknown physiological and pathological functions. We identified the novel ubiquitin ligase HRD1 involved in ERAD. HRD1 is expressed in brain neurons and protects against ER stress-induced apoptosis. In familial Parkinson's disease, accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of ubiquitin ligase Parkin involved in ERAD, causes ER stress and apoptosis. We demonstrated that HRD1 promotes ubiquitination and degradation of Pael-R and suppresses ER stress and apoptosis induced by Pael-R. Amyloid precursor protein (APP) is processed into amyloid beta (Abeta) in Alzheimer's disease. We found that HRD1 promotes APP ubiquitination and degradation, resulting in decreased generation of Abeta. Furthermore, suppression of HRD1 expression causes APP accumulation and Abeta generation associated with ER stress and apoptosis. Interestingly, HRD1 protein levels significantly decreased in the cerebral cortex of Alzheimer's disease patients, possibly because of its insolubilization. We demonstrated that HRD1 protein was insolubilized by oxidative stress, resulting in the accumulation of HRD1 into the aggresome. In conclusion, oxidative stress-induced HRD1 insolubilization might be involved in a vicious cycle of increased Abeta production and Abeta-induced oxidative stress in Alzheimer's disease pathogenesis. PMID- 27252060 TI - ER Stress-induced Aberrant Neuronal Maturation and Neurodevelopmental Disorders. AB - Neurodevelopmental disorders, which include autism spectrum disorder, are congenital impairments in the growth and development of the central nervous system. They are mainly accentuated during infancy and childhood. Autism spectrum disorder may be caused by environmental factors, genomic imprinting of chromosome 15q11-q13 regions, and gene defects such as those in genes encoding neurexin and neuroligin, which are involved in synaptogenesis and synaptic signaling. However, regardless of the many reports on neurodevelopmental disorders, the pathogenic mechanism and treatment of neurodevelopmental disorders remain unclear. Conversely, it has been reported that endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases. ER stress is increased by environmental factors such as alcohol consumption and smoking. Here we show the recent results on ER stress-induced neurodevelopmental disorders. ER stress led to a decrease in the mRNA levels of the proneural factors Hes1/5 and Pax6, which maintain an undifferentiated state of the neural cells. This stress also led to a decrease in nestin expression and an increase in beta-III tubulin expression. In addition, dendrite length was shortened by ER stress in microtubule-associated protein-2 (MAP-2) positive cells. However, the ubiquitin ligase HRD1 expression was increased by ER stress. By suppressing HRD1 expression, the ER stress-induced decrease in nestin and MAP-2 expression and increase in beta-III tubulin returned to control levels. Therefore, we suggest that ER stress induces abnormalities in neuronal differentiation and maturation via HRD1 expression. These results suggest that targeting ER stress may facilitate quicker approaches toward the prevention and treatment of neurodevelopmental disorders. PMID- 27252061 TI - Pathogenic Mechanism of Diabetes Development Due to Dysfunction of Unfolded Protein Response. AB - The endoplasmic reticulum (ER) is an organelle in which newly synthesized secretory and membrane proteins are folded and assembled. Various stresses cause the accumulation of unfolded or misfolded proteins in the ER, resulting in ER dysfunction. This condition is termed ER stress. To cope with ER stress, cells activate a signaling pathway termed the unfolded protein response (UPR). Recently, accumulating evidence suggests that the UPR plays a pivotal role in pancreatic beta cells. Pancreatic beta cells producing a large amount of insulin are highly sensitive when the UPR is impaired. In mammalian cells, three principal ER stress sensors, PERK, IRE1, and ATF6, initiate the UPR. Activated PERK attenuates protein translation through eIF2alpha phosphorylation to cope with the ER stress. PERK KO mice develop diabetes by 2-4 weeks of age due to progressive beta-cell loss. IRE1alpha noncanonically splices the XBP1 mRNA, leading to the upregulation of the ERAD components and ER molecular chaperones. This pathway is constitutively activated in pancreatic beta cells. To clarify the physiological role of the IRE1alpha pathway in beta cells, we generated pancreatic-beta-cell-specific IRE1alpha-conditional KO (cKO) mice and IRE1alpha cKO insulinoma cell lines. Here, we show that IRE1alpha is required for the upregulation of insulin-folding enzymes in pancreatic beta cells to balance insulin-folding enzymes with insulin. PMID- 27252062 TI - The Mechanisms and Pharmacological Strategy for Treatment of ER Stress-induced Metabolic Syndrome. AB - Obesity is one of the major risk factors of metabolic syndrome, such as hypertension, hyperlipidemia, and diabetes. Leptin exerts an anti-obesity effect through the Ob-Rb leptin receptor, which is mainly expressed on hypothalamic neuronal cells. Recent evidence indicated that one of the mechanisms of obesity may be the development of leptin resistance. In the present review, we discuss the mechanisms of leptin resistance in obesity, focusing on endoplasmic reticulum (ER) stress. We previously found that flurbiprofen is a candidate drug for attenuating ER stress and the subsequent development of leptin resistance. We will discuss a possible pharmacological strategy for treating obesity by ameliorating ER stress. PMID- 27252063 TI - Application of Unfolded Protein Response for Production of Biologics. AB - Improvements in the productivity of established mammalian cell lines used for biopharmaceutical production are desirable to increase product yields. Chinese hamster ovary (CHO) cells are the workhorse used for more than 60% of industrial therapeutic antibody production. Glycoprotein secretion by CHO cells requires intracellular processes including transcription, translation, glycosylation, and secretion. Within these intracellular steps, post-translational processes are rate limiting for production in high-producer cell lines. This review focuses on unfolded protein response-based engineering of CHO cells and details our recent progress in using overexpression of activating transcription factor 4 to promote recombinant protein production. PMID- 27252064 TI - Syntheses and Reactions of Chalcogen-containing Heterocycles. AB - The advances in my laboratory for the past 20-25 years concerning the chemistry of chalcogen-containing heterocycles are reviewed. The intramolecular cyclization of the chalcogenols (-TeH, -SeH, -SH) into a triple bond or appropriate leaving group produced various chalcogen-containing heterocycles. The reactions of the obtained products were examined: the reactions of 1-benzo- and 2-benzopyrylium salts containing a tellurium or selenium element with several nucleophiles, including alkoxides, amines, the cyanide ion, an active methyl compound (acetone), Grignard reagents, copper reagents, and tin reagents, along with hydrogenation and hydrolysis reactions, provided corresponding chromes or isochromes having various functional groups at the 2- or 1-C position. Isothiocyanate and isoselenocyanate were used as chalcogen sources for the preparation of five- or six-membered heterocycles. In addition, double intramolecular cyclization, ring-expansion reactions, electrophilic cyclization and iodocyclization were also carried out. PMID- 27252065 TI - Induction of Aneuploidy, Centrosome Abnormality, Multipolar Spindle, and Multipolar Division in Cultured Mammalian Cells Exposed to an Arsenic Metabolite, Dimethylarsinate. AB - Toxicological studies of arsenic compounds were conducted in cultured mammalian cells to investigate the effects of glutathione (GSH) depletion. Dimethylarsinate DMA(V) was not cytotoxic in cells depleted of GSH, but was found to be cytotoxic when GSH was present outside the cells. The results suggested that a reactive form of DMA(V) was generated through interaction with GSH. Dimethylarsine iodide DMI(III) was used as a model compound of DMA(III), and the biological effects were investigated. DMI(III) was about 10000 times more toxic to the cells than DMA(V). Chromosome structural aberrations and numerical changes, such as aneuploidy, were induced by DMI(III). DMA(V) induced multiple foci of the centrosome protein, gamma-tubulin, which were colocalized with multipolar spindles in mitotic cells. The multiple foci coalesced into a single dot on disruption of the microtubules (MT). However, reorganization of the MT caused multiple foci of gamma-tubulin, suggesting that the induction of centrosome abnormalities by DMA(V) required intact MT. Inhibition of the MT-dependent motor, kinesin, prevented formation of multiple foci of gamma-tubulin, which pointed to the involvement of the MT-dependent mitotic motor, kinesin, in the maintenance of centrosome abnormalities. DMI(III) caused abnormal cytokinesis (multipolar division). In addition, DMI(III) caused morphological transformation in Syrian hamster embryo cells. Consideration of the overall process following the centrosome abnormalities caused by DMA(V) suggested a mode of cytotoxicity in which the mitotic centrosome is a critical target. PMID- 27252066 TI - Reaction Development on pi- and sigma-Conjugated Bonds and Creation of Innovative Functions. AB - Monocarba-closo-dodecaborate (1; [closo-CB11H12](-), or C1-carborane anion) is a symmetrical, stable anionic cluster, which possesses low nucleophilicity/basicity and exhibits three-dimensional aromaticity. In contrast to the rich applications of C2-carborane molecules (C2B10H12), the chemistry of the C1-carborane anion as a platform for functional molecules has not been thoroughly studied thus far due to the lack of its efficient functionalization. In particular, no efficient general methods are available for the introduction of aryl and sp(2)/sp-carbon groups at the carbon vertex of the C1-carborane anion. The unique electronic structure and potential applications of the C1-carborane anion prompted us to investigate methods to functionalize it. We developed a general, efficient C-C cross-coupling reaction of 1 under palladium catalysis which yields a variety of 1-C-functionalized C1-carborane derivatives. The use of copper(I) or lithium species as a transmetalating partner facilitated the cross-coupling process of the sterically hindered C1-carborane anion. The potential application of 1-C arylated C1-carborane anion derivatives thus obtained were explored, some of which showed potential as pharmacophores and ionic liquid crystal behavior. Furthermore, conjugation between sigma- and pi-aromatic moieties in 1-C-arylated monocarba-closo-dodecaborate anion derivatives was identified by means of kinetic experimental studies combined with theoretical calculations. PMID- 27252067 TI - Animal Models for Elucidation of the Mechanisms of Neuropsychiatric Disorders Induced by Sleep and Dietary Habits. AB - Numerous changes in human lifestyle in modern life increase the risk of disease. Especially, modern sleep and dietary habits are crucial factors affecting lifestyle disease. In terms of sleep, decreases in total sleep time and in rapid eye movement sleep time have been observed in attention-deficit/hyperactivity disorder (ADHD) patients. From a dietary perspective, mastication during eating has several good effects on systemic, mental, and physical functions of the body. However, few animal experiments have addressed the influence of this decline in sleep duration or of long-term powdered diet feeding on parameters reflecting systemic health. In our studies, we examined both the influence of intermittent sleep deprivation (SD) treatment and long-term powdered diet feeding on emotional behavior in mice, and focused on the mechanisms underlying these impaired behaviors. Our findings were as follows: SD treatment induced hypernoradrenergic and hypodopaminergic states within the frontal cortex. Furthermore, hyperactivity and an explosive number of jumps were observed. Both the hypernoradrenergic state and the jumps were improved by treatment with ADHD therapeutic drugs. On the other hand, long-term powdered diet feeding increased social interaction behaviors. The feeding affected the dopaminergic function of the frontal cortex. In addition, the long-term powdered diet fed mice presented systemic illness signs, such as elevations of blood glucose, and hypertension. This review, describing the SD mice and long-term powdered diet fed mice can be a useful model for elucidation of the mechanism of neuropsychiatric disorders or the discovery of new therapeutic targets in combatting effects of the modern lifestyle. PMID- 27252068 TI - Pharmacokinetic and Pharmacodynamic Analyses of Drug-Drug Interactions between Iguratimod and Warfarin. AB - Iguratimod (IGU), a disease-modifying antirheumatic drug launched in September 2012, has been reported to carry a risk of severe hemorrhages through a suspected interaction with warfarin (WF) in the all-case surveillance and early postmarketing-phase vigilance. To elucidate possible mechanisms of adverse interaction between IGU and WF, we analyzed the effects of IGU on the pharmacodynamics and pharmacokinetics of WF in rats. IGU was orally administered to male Wistar rats once daily for 5 d at 10 or 30 mg/kg in combination with WF at an oral dose of 0.25 mg/kg. Coadministration of IGU 30 mg/kg enhanced the anticoagulant activity of WF; prolonged blood coagulation time (prothrombin time and activated partial thromboplastin time) and decreased levels of vitamin K (VK) dependent blood coagulation factors (II, VII, IX, and X) were observed. On the other hand, the pharmacokinetic parameters of WF including maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC0-24 h) were not affected by the combination with IGU. IGU alone did not change blood coagulation time at doses up to 100 mg/kg, while VK-dependent blood coagulation factors decreased slightly at 30 and 100 mg/kg. These results suggest that the pharmacodynamic effect of IGU on VK-dependent blood coagulation factors is involved in the mechanism of drug-drug interaction of IGU with WF. PMID- 27252069 TI - An Approach for Safe Medication Assistance in Nursing Homes: A Workshop to Identify Problems of and Plan Measures for Care Workers. AB - We conducted a workshop that aimed to clarify problems with care workers supporting medication use in nursing homes, to propose measures for solving these problems, and to raise awareness of these problems among care workers. Eighteen care workers from different fee-based elderly nursing homes were enrolled in the workshop, and divided into four groups. The participants in these groups identified the issues based on their experiences regarding medication-related incidents, and discussed related problems and viable measures using the KJ method. The issues identified by each group were "dropping a medication", "wrong resident", "refusal to take medication", and "confusion". To resolve these problems, the participants recommended: "conducting study sessions or testing of manuals and medication knowledge", "strengthening monitoring systems", "enhancing information sharing", etc. The involvement of pharmacists was hardly mentioned, despite the workshop being designed for "medication assistance". A post-workshop questionnaire revealed that 88.9% of the participants acknowledged an increased awareness of safe assistance in the use of medication. A follow-up questionnaire, distributed approximately seven months after the workshop, revealed that 82.4% of participants applied the experience and knowledge they learned at the workshop to their work. The workshop seemed to raise awareness and lead to preventive measures for safe medication assistance. Communication between care workers and other health care professionals, such as pharmacists, is important to designing and implementing safe medical care in nursing homes. PMID- 27252070 TI - Pharmaceutical Approach for the Diagnosis and Treatment of Malignant Syndrome: A Case Study. AB - Since 2012, Matsudo City Hospital has increased the number of pharmacists stationed in the ward on weekday mornings at the emergency care center, the intensive care unit (ICU) and the high care unit (HCU). Multidisciplinary joint meetings and joint conferences are conducted in the emergency care center, and patient and drug information is shared. A 20-year-old man was transferred to our hospital after a traffic accident. He was diagnosed with subarachnoid hemorrhage and brain contusion. He exhibited violent movement and intense restlessness. He was sedated with a continuous intravenous infusion of 5 mg/h midazolam and 20 MUg/h fentanyl, with intubation. Propofol was also used intermittently. The midazolam infusion was concluded on day 5 of hospitalization. However, his restlessness recurred so an intravenous drip infusion of 150 mg/h haloperidol was administered. On the 7th day, he developed a high-grade fever, muscle rigidity, perspiration, and leukocytosis, and malignant syndrome or malignant hyperthermia was suspected. For malignant syndrome treatment, he received an intravenous drip infusion of 60 mg dantrolene, followed by the combined oral administration of 100 mg/d dantrolene and 7.5 mg/d bromocriptine. Considering various pharmacological effects, we selected an intravenous drip infusion of 25 mg hydroxyzine hydrochloride as the drug to alleviate restlessness. The patient's course continued without recurrence of malignant syndrome; his symptoms improved because of pharmaceutical care with an awareness of patient benefits through clinical and laboratory findings, consultation with the attending physician, presentation of information on causative and therapeutic drugs, and coordinated planning of a prescription design. PMID- 27252071 TI - Proteolysis in plasmid DNA stable maintenance in bacterial cells. AB - Plasmids, as extrachromosomal genetic elements, need to work out strategies that promote independent replication and stable maintenance in host bacterial cells. Their maintenance depends on constant formation and dissociation of nucleoprotein complexes formed on plasmid DNA. Plasmid replication initiation proteins (Rep) form specific complexes on direct repeats (iterons) localized within the plasmid replication origin. Formation of these complexes along with a strict control of Rep protein cellular concentration, quaternary structure, and activity, is essential for plasmid maintenance. Another important mechanism for maintenance of low-copy-number plasmids are the toxin-antitoxin (TA) post-segregational killing (psk) systems, which prevent plasmid loss from the bacterial cell population. In this mini review we discuss the importance of nucleoprotein complex processing by energy-dependent host proteases in plasmid DNA replication and plasmid type II toxin-antitoxin psk systems, and draw attention to the elusive role of DNA in this process. PMID- 27252072 TI - An Internet-Based Intervention to Promote Alcohol-Related Attitudinal and Behavioral Change Among Adolescents: Protocol of a Cluster Randomized Controlled Trial. AB - BACKGROUND: Underage drinking is a prevalent risk behavior and common public health problem. Research shows that alcohol abuse not only affects the quality of life of drinkers themselves. The problems resulting from underage drinking pose substantial costs to society as well. The proposed study will address underage drinking with the use of an Internet campaign, which is a cost-effective way of tackling the problem. OBJECTIVE: The aims of this study are to test the effectiveness of an online quiz competition in changing adolescents' alcohol related attitudes and behavior and to explore the feasibility of using Internet viral marketing to reach a significant number of adolescents. METHODS: The study will constitute a cluster randomized controlled trial for 20 secondary schools (6720 Grade 7-9 students). Schools will be randomized to intervention or control arm with equal likelihood. Students in intervention schools will be invited to take part in the Internet campaign, whereas those in control schools will receive relevant promotional leaflets. RESULTS: Alcohol-related attitude and behavior will be the primary outcome measures. The results of the proposed study will provide evidence on the efficacy of an Internet intervention in modifying adolescents' attitudes and behavior and guide further investigation into the prevention of and intervention in such risk behaviors as underage drinking. The project was funded July 2015, enrollment started September 2015, and results are expected July 2017. CONCLUSIONS: With the Internet increasingly being recognized as a practical and cost-effective platform for health information delivery, the proposed Internet-based intervention is expected to be more effective in altering adolescents' alcohol-related attitudes and behaviors than traditional health promotion. CLINICALTRIAL: ClinicalTrials.gov NCT02450344; https://clinicaltrials.gov/ct2/show/NCT02450344 (Archived by WebCite at http://www.webcitation.org/6heB2zMBD). PMID- 27252073 TI - Magnetic targeted drug delivery carriers encapsulated with pH-sensitive polymer: synthesis, characterization and in vitro doxorubicin release studies. AB - Targeted and efficient delivery of drug to tumor is one of the crucial issues in cancer therapy. In this work, we have successfully designed and prepared the pH sensitive magnetic nanoparticles (MNPs) as targeted anticancer drug carriers, in which the MNPs were coated by poly(acrylic acid) (PAA) and the obtained PAA@MNPs exhibited a size within 100 nm, good stability, and superparamagnetic responsibility (Ms 45.97 emu/g). Doxorubicin (DOX) can be successfully loaded onto MNPs via electrostatic interaction, and the drug loading content and loading efficiency are 26.4 and 88.1%, respectively. Moreover, the release studies showed that the drug-loaded carriers (MNPs-DOX) had excellent pH sensitivity, 75.6% of the loaded DOX was released at pH 4.0 within 48 h. Importantly, MTT assays in HUVEC and MCF-7 cells demonstrated that MNPs-DOX exhibited high anti-tumor activity, while the PAA@MNPs were practically nontoxic. Thus, our results revealed that PAA@MNPs would be a competitive candidate for biomedical application and MNPs-DOX could be used in targeted cancer therapy. PMID- 27252074 TI - The Chinese Herbal Mixture Tien-Hsien Liquid Augments the Anticancer Immunity in Tumor Cell-Vaccinated Mice. AB - BACKGROUND: The Chinese herbal mixture, Tien-Hsien liquid (THL), has been used as an anticancer dietary supplement for more than 20 years. Our previous studies have shown that THL can modulate immune responseand inhibit tumor growth. In this study, we further evaluated the effect of THL on anticancer immune response in mice vaccinated with gamma-ray-irradiated tumor cells. METHODS: The antitumor effect of THL was determined in mice vaccinated with low-tumorigenic CT-26-low colon cancer cells or gamma-ray-irradiated high-tumorigenic CT-26-high colon cancer cells. The number of natural killer (NK) cells and T lymphocytes in the spleen was analyzed by flow cytometry. The tumor-killing activities of NK cells and cytotoxic T lymphocytes (CTLs) were analyzed by flow cytometry using YAC-1 and CT-26-high cells, respectively, as target cells. The levels of IFN-gamma, IL 2, and TNF-alpha were determined by ELISA. RESULTS: THL suppressed the growth of CT-26-high tumor in mice previously vaccinated with low-tumorigenic CT-26-low cells or gamma-irradiated CT-26-high cells. THL increased the populations of NK cells and CD4+ T lymphocytes in the spleen and enhanced the tumor-killing activities of NK cells and CTL in mice vaccinated with gamma-irradiated CT-26 high cells. THL increased the production of IFN-gamma, IL-2, and TNF-alpha in mice vaccinated with gamma-irradiated CT-26-high cells. CONCLUSION: THL can enhance the antitumor immune responses in mice vaccinated with killed tumor cells. These results suggest that THL may be used as a complementary medicine for cancer patients previously treated with killed tumor cell vaccines, radiotherapy, or chemotherapy. PMID- 27252075 TI - Use of Mindfulness Sitting Meditation in Chinese American Women in Treatment of Cancer. AB - BACKGROUND: Very few studies have been conducted to examine the prevalence, frequency, perceived effectiveness, and possible influencing factors of use of meditation in patients with cancer. OBJECTIVES: To examine use of mindfulness sitting medication (MSM) in Chinese American women in treatment of cancer, its relationship to specific symptom distress, and possible influencing factors of MSM. METHODS: Volunteer participants were recruited through the American Cancer Society support groups. The participants completed a demographic data form, a researcher-developed criteria and checklist for MSM, and the Memorial Symptom Assessment Scale-Short Form. RESULTS: Eighty-nine Chinese American women with a mean age of 58 years completed the questionnaires. Twenty-one patients (24%) reported the use of MSM during active treatment of cancer. Patients who had higher education, better income, better English proficiency, and health insurance were more likely to use MSM. Patients who had more symptom distress also reported to use more MSM. Most patients (20/21) who used meditation considered it effective. After controlling other variables, better English proficiency, breast cancer, and higher symptom distress predicted the use of MSM in Chinese American women in treatment of cancer. CONCLUSIONS: About 24% of Chinese American women used MSM in the treatment of cancer and most of them considered it effective. Symptom distress and English proficiency levels predicted the use of MSM. IMPLICATIONS FOR PRACTICE: Given the effectiveness of MSM, oncology nurses could recommend using MSM in Chinese American women in treatment of cancer, especially for patients who had higher symptom distress. PMID- 27252076 TI - Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors. AB - HYPOTHESES: Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. STUDY DESIGN: We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. METHODS: 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. RESULTS: The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. CONCLUSION: Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour. PMID- 27252077 TI - A Prospective Randomized Controlled Trial to Study the Impact of a Nutrition Sensitive Intervention on Adult Women With Cancer Cachexia Undergoing Palliative Care in India. AB - PURPOSE: Advanced cancer patients with disease progression develop cachexia. Nevertheless, cancer patients at nutritional risk have shown improved body weight and quality of life with oral nutritional supplements. METHOD: This was a randomized controlled trial in adult female cancer patients (n = 63) attending palliative clinics, with symptoms of cachexia. Eligible patients were randomly distributed into control (n = 33) and intervention (n = 30) groups. Both groups were provided with nutritional and physical activity counseling, but the intervention group received an additional 100 g of Improved Atta (IAtta) for 6 months daily consumption. This study was designed to assess the efficacy of IAtta (with counseling) in enhancing the health status of cachexic patients. Anthropometric measurements, dietary intake, physical activity level and quality of life parameters were assessed at baseline, after 3 months, and at the end of 6 months. RESULTS: Patients in the control group (n = 15) had significantly decreased body weight ( P = .003), mid-upper-arm circumference ( P = .002), and body fat ( P = .002) by the end of intervention. A trend of body weight gain in the intervention group (n = 17; P = .08) and significant increase of body fat ( P = .002) was observed; moreover, patients reported a significant improvement in fatigue ( P = .002) and appetite scores ( P = .006) under quality-of-life domains at the end of intervention. CONCLUSIONS: Embedding a nutrition-sensitive intervention ( IAtta ) within Indian palliative care therapy may improve quality of life and stabilize body weight in cancer cachexia patients. PMID- 27252079 TI - Multiplexed Cassegrain Reflector Antenna for Simultaneous Generation of Three Orbital Angular Momentum (OAM) Modes. AB - A multiplexed Cassegrain reflector antenna with a 2 * 2 open-ended rectangular waveguide (OERW) matrix feed and an orbital angular momentum (OAM) mode mux is proposed for the simultaneous generation of three OAM modes (l = 0, +/-1). The OAM mode mux (OMM) was designed using sequential combinations of quadrature hybrids, crossovers, and phase shifters to multiplex and demultiplex three OAM modes at the same time. The 2 * 2 OERW matrix feed and the OMM were separately measured and their performances were verified according to proposed theories. A near-field antenna measurement for a multiplexed Cassegrain reflector antenna was conducted to obtain the far-field magnitude and phase patterns around polar elevation angle theta and azimuthal angle phi, thus confirming that our antenna can produce three OAM modes simultaneously. We also measured the communication link characteristics of two identical multiplexed antennas. The measurement results show that the channel isolation of three OAM modes is more than 12.7 [dB] and 17 [dB] for fixed and compensated receiver positions, respectively, indicating that the proposed antenna system can be used for independent communication links with the same frequency and polarisation. PMID- 27252078 TI - Prevalence of Abdominal Aortic Aneurysm in Men Aged 65-74 Years in a Metropolitan Area in North-East Spain. AB - BACKGROUND: A declining prevalence of AAA and a shift in the distribution towards the older population have been observed during the last decade in Europe. The aim was to estimate the current screening prevalence of AAA in men aged 65-74 years in a metropolitan area in north-east Spain and to identify associated risk factors. METHODS: A cross sectional prevalence study in men registered in L'Hospitalet Primary Healthcare Services (Barcelona, Spain) was performed. There were 619 randomly selected subjects (expected prevalence of aneurysm, 5%; accuracy of estimation, +/-2%; loss to follow up, 30%). Exclusion criteria were life expectancy <1 year, limited quality of life, previous diagnosis of AAA, prior aorto-femoral surgery, and non-Caucasian. The following were measured: internal diameter of the infrarenal abdominal aorta using ultrasound, cardiovascular risk factors, personal (heart disease, stroke, peripheral vascular disease) and family history (AAA), physical examination, and blood tests. We estimated the prevalence and 95% confidence interval of AAA, and used logistic regression analysis to identify risk factors for AAA. RESULTS: Among the 651 individuals included in the analysis the prevalence of aneurysm was 2.30% (95% CI, 1.30-3.77%). In the regression analysis, AAA was associated with smoking (0 10, 11-20, or >20 cigarettes/day), diagnosis of myocardial infarction, and being taller than the median (165 cm). CONCLUSIONS: The current screening prevalence of AAA among men aged 65-74 years in a metropolitan area in north-east Spain is similar to that in northern Europe. Smoking, myocardial infarction, and height were associated with the presence of AAA. PMID- 27252080 TI - Vasorelaxant mode of action of dichloromethane-soluble extract from Agastache mexicana and its main bioactive compounds. AB - CONTEXT: Agastache mexicana (Kunth) Lint & Epling (Lamiaceae) is a plant used in Mexican traditional medicine for the treatment of hypertension, anxiety and so on. OBJECTIVE: To determine the vasorelaxant effect and functional mode of action of dichloromethane-soluble extract from A. mexicana (DEAm) and isolate the constituents responsible for the pharmacological activity. MATERIALS AND METHODS: Extracts were prepared from the aerial parts of A. mexicana (225.6 g) by successive maceration with hexane, dichloromethane and methanol (three times for 72 h at room temperature), respectively. DEAm (0.01-1000 MUg/mL), fractions (at 174.27 MUg/mL), acacetin and ursolic acid (UA) (0.5-500 MUM) were evaluated to determine their vasorelaxant effect on ex vivo rat aorta ring model. In vivo UA antihypertensive action was determined on spontaneously hypertensive rats. RESULTS AND DISCUSSION: DEAm induced a significant vasorelaxant effect in concentration-dependent and endothelium-independent manners (EC50 = 174.276 +/- 5.98 MUg/mL) by a calcium channel blockade and potassium channel opening. Bio guided fractionation allowed to isolate acacetin (112 mg), UA (2.830 g), acacetin/oleanolic acid (OA) (M1) (155 mg) and acacetin/OA/UA (M2) (1.382 g) mixtures, which also showed significant vasodilation. UA significantly diminished diastolic (80 mmHg) and systolic blood pressure (120 mmHg), but heart rate was not modified. CONCLUSION: DEAm produced significant vasorelaxant action by myogenic control cation. The presence of acacetin, OA and UA into the extract was substantial for the relaxant activity of DEAm. In vivo antihypertensive action of UA corroborates the use of A. mexicana as an antihypertensive agent on Mexican folk medicine. PMID- 27252081 TI - Interfaces between mitochondrial dynamics and disease. AB - In the cellular context, mitochondria display a number of dynamic behaviors including fusion, division (or fission), directed transport, and targeted destruction (mitophagy). The relevance of these processes to human diseases has been intensively studied over the last several years, and emphasize the importance of mitochondrial dynamics to the central nervous system. Intriguingly, a common theme is that these behaviors do not function in isolation, but influence one another either directly or indirectly. Here, we review the dynamic properties of mitochondria and summarize their relationships to human diseases. PMID- 27252082 TI - Sequential morphometric evaluation at UnicCa(r) and DCD(r) implant surfaces. An experimental study in the dog. AB - AIM: To study tissue components adjacent to implants with nanotechnologically modified surfaces at different periods of healing. MATERIAL & METHODS: In 12 beagle dogs, two different implant systems with different surface configurations were randomly installed in the edentulous premolar regions of the mandible. One surface was first acid-etched and subsequently, nanotechnologically modified with calcium ions (UnicCa(r) ), while the other was first sandblasted and acid-etched, and then additionally treated with a nanometer calcium phosphate deposition (discrete crystalline deposition; DCD(r) ). The implants were fully submerged; surgeries and sacrifices were planned to harvest biopsies after 1, 2, 4 and 8 weeks of healing (n = 6 per period). A morphometric evaluation of percentages of new and old bone, bone debris/particles and clot, new soft tissues (provisional matrix and immature marrow), mature bone marrow and vessels was performed in the spongiosa compartment adjacent to the implant surface up to a distance of about 0.4 mm from the surface. RESULTS: After 2 weeks of healing, the soft tissues were represented by 41.0% at the UnicCa(r) and 37.9% at the DCD(r) surfaces, in both cases mainly being composed of provisional matrix. These percentages decreased over time, being composed of greater amounts of immature bone marrow, and disappeared after 8 weeks. New bone increased progressively between 1 and 8 weeks of healing from 9.7 +/- 6.3% to 70.0 +/- 8.4% and from 8.2 +/- 3.5% to 67.0 +/- 6.1% at the UnicCa(r) and DCD(r) surfaces, respectively. Pristine bone was progressively resorbed. CONCLUSIONS: Throughout the periods of healing observed, the formation of a provisional matrix followed by the formation of new bone and marrow was revealed in a similar fashion as for other modified surface configurations. PMID- 27252083 TI - Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations. AB - Although telomere length is genetically determined, mouse embryonic stem (ES) cells with telomeres of twice the normal size have been generated. Here, we use such ES cells with 'hyper-long' telomeres, which also express green fluorescent protein (GFP), to generate chimaeric mice containing cells with both hyper-long and normal telomeres. We show that chimaeric mice contain GFP-positive cells in all mouse tissues, display normal tissue histology and normal survival. Both hyper-long and normal telomeres shorten with age, but GFP-positive cells retain longer telomeres as mice age. Chimaeric mice with hyper-long telomeres also accumulate fewer cells with short telomeres and less DNA damage with age, and express lower levels of p53. In highly renewing compartments, such as the blood, cells with hyper-long telomeres are longitudinally maintained or enriched with age. We further show that wound-healing rates in the skin are increased in chimaeric mice. Our work demonstrates that mice with functional, longer and better preserved telomeres can be generated without the need for genetic manipulations, such as TERT overexpression. PMID- 27252085 TI - Residual beta activity of particulate (234)Th as a novel proxy for tracking sediment resuspension in the ocean. AB - Sediment resuspension occurs in the global ocean, which greatly affects material exchange between the sediment and the overlying seawater. The behaviours of carbon, nutrients, heavy metals, and other pollutants at the sediment-seawater boundary will further link to climate change, eutrophication, and marine pollution. Residual beta activity of particulate (234)Th (RAP234) is used as a novel proxy to track sediment resuspension in different marine environments, including the western Arctic Ocean, the South China Sea, and the Southern Ocean. Sediment resuspension identified by high activity of RAP234 is supported by different lines of evidence including seawater turbidity, residence time of total (234)Th, Goldschmidt's classification, and ratio of RAP234 to particulate organic carbon. A conceptual model is proposed to elucidate the mechanism for RAP234 with dominant contributions from (234)Th-(238)U and (212)Bi-(228)Th. The 'slope assumption' for RAP234 indicated increasing intensity of sediment resuspension from spring to autumn under the influence of the East Asian monsoon system. RAP234 can shed new light on (234)Th-based particle dynamics and should benefit the interpretation of historical (234)Th-(238)U database. RAP234 resembles lithophile elements and has broad implications for investigating particle dynamics in the estuary-shelf-slope-ocean continuum and linkage of the atmosphere ocean-sediment system. PMID- 27252084 TI - Tomato 26S Proteasome subunit RPT4a regulates ToLCNDV transcription and activates hypersensitive response in tomato. AB - Involvement of 26S proteasomal subunits in plant pathogen-interactions, and the roles of each subunit in independently modulating the activity of many intra- and inter-cellular regulators controlling physiological and defense responses of a plant were well reported. In this regard, we aimed to functionally characterize a Solanum lycopersicum 26S proteasomal subunit RPT4a (SlRPT4) gene, which was differentially expressed after Tomato leaf curl New Delhi virus (ToLCNDV) infection in tolerant cultivar H-88-78-1. Molecular analysis revealed that SlRPT4 protein has an active ATPase activity. SlRPT4 could specifically bind to the stem loop structure of intergenic region (IR), present in both DNA-A and DNA-B molecule of the bipartite viral genome. Lack of secondary structure in replication-associated gene fragment prevented formation of DNA-protein complex suggesting that binding of SlRPT4 with DNA is secondary structure specific. Interestingly, binding of SlRPT4 to IR inhibited the function of RNA Pol-II and subsequently reduced the bi-directional transcription of ToLCNDV genome. Virus induced gene silencing of SlRPT4 gene incited conversion of tolerant attributes of cultivar H-88-78-1 into susceptibility. Furthermore, transient overexpression of SlRPT4 resulted in activation of programmed cell death and antioxidant enzymes system. Overall, present study highlights non-proteolytic function of SlRPT4 and their participation in defense pathway against virus infection in tomato. PMID- 27252086 TI - The histology of skin treated with a picosecond alexandrite laser and a fractional lens array. AB - BACKGROUND AND OBJECTIVES: The treatment of acne scars and wrinkles with a picosecond Alexandrite laser was recently FDA cleared. In 2014 we presented our initial histologic findings with this device on in vivo and ex vivo skin. This current study expands on the 2014 pilot study with an investigation of different energy settings using histology and the confocal microscope to describe the changes observed in the skin. MATERIALS AND METHODS: We used a 755 nm picosecond Alexandrite laser with a fractional optic with three different energy settings to treat in vivo. After treatment, the patients and skin samples were also evaluated with a confocal microscope followed by biopsies which were evaluated histologically. RESULTS: Histology revealed unique intra-epidermal cavities. The number, density, and the size of these cavities were dependent on the melanin index and delivered energy when evaluated with histopathology and the confocal microscope. These localized zones of injury appear to form microscopic epidermal injury zones which are exfoliated over a 3-week period. CONCLUSIONS: These intra epidermal cavities result from areas of laser-induced optical breakdown (LIOB). This injury is most consistent with a localized plasma formation in the epidermis initiated by the melanin absorption of the high energy picosecond light. It appears that treatments with this device and optic result in improvements in dyspigmentation and acne scars with new collagen, elastic tissue, and mucin. The production of this LIOB could directly stimulate an epidermal repair mechanism that results in these clinical findings. Lasers Surg. Med. 48:646-652, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27252087 TI - Mass Spectrometric Observation of Doubly Charged Alkaline-Earth Argon Ions. AB - Doubly charged diatomic ions MAr(2+) where M=Mg, Ca, Sr or Ba have been observed by mass spectrometry with an inductively coupled plasma ion source. Abundance ratios are quite high, 0.1 % for MgAr(2+) , 0.4 % for CaAr(2+) , 0.2 % for SrAr(2+) and 0.1 % for BaAr(2+) relative to the corresponding doubly charged atomic ions M(2+) . It is assumed that these molecular ions are formed through reactions of the doubly charged metal ions with neutral argon atoms within the ion source. Bond dissociation energies (D0 ) were calculated and agree well with previously published values. The abundance ratios MAr(+) /M(+) and MAr(2+) /M(2+) generally follow the predicted bond dissociation energies with the exception of MgAr(2+) . Mg(2+) should form the strongest bond with Ar [D0 (MgAr(2+) )=124 to 130 kJ mol(-1) ] but its relative abundance is similar to that of the weakest bound BaAr(2+) (D0 =34 to 42 kJ mol(-1) ). The relative abundances of the various MAr(2+) ions are higher than those expected from an argon plasma at T=6000 K, indicating that collisions during ion extraction reduce the abundance of the MAr(2+) ions relative to the composition in the source. The corresponding singly charged MAr(+) ions are also observed but occur at about three orders of magnitude lower intensity than MAr(2+) . PMID- 27252088 TI - A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two-step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin. AB - Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world-wide. However, the key UDP-dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two-step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site-directed mutagenesis revealed that Gln-352 may be important for the initial step of glucuronosylation, and His-22, Trp-370, Glu-375 and Gln 392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two-step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin. PMID- 27252089 TI - General anesthetics and cytotoxicity: possible implications for brain health. AB - BACKGROUND: The search for agents that bring about faster induction and quicker recovery in the operating room have yielded numerous anesthetics whose mechanisms of action and potential toxic side effects remain unknown, especially in the young and aging brain. OBJECTIVE: Taking advantage of our clinical and basic science expertise, here we subject the reader to an interesting perspective vis-a vis the current applications of general anesthetics, and present evidence for their neurotoxic effects on the developing and elderly brains. RESULTS: Recent studies have called into question the safety of general anesthetics, especially with regards to potentially significant detrimental impacts on the developing brains of young children, and cognitive decline in the elderly - often following multiple episodes of anesthesia. Despite accumulating evidence from animal studies demonstrating that general anesthesia leads to neurodegeneration and cognitive impairment, to date a clear consensus on the impact of anesthetics in humans remains elusive. Because a direct impact of anesthetics on human neuronal networks is often difficult to deduce experimentally, most laboratories have resorted to animal models - albeit with limited success in translating these findings back to the clinic. Moreover, the precise mechanisms that lead to potential cognitive, learning, and memory decline in young and elderly patients also remain to be fully defined. CONCLUSIONS: This review will focus primarily on the cytotoxic effects of anesthetics, and offer some practical resolutions that may attenuate their long-term harm. An urgent need for studies on animal models and an increased focus on highly controlled prospective epidemiological studies is also reinforced. PMID- 27252090 TI - Comparison of a single-channel EEG sleep study to polysomnography. AB - An accurate home sleep study to assess electroencephalography (EEG)-based sleep stages and EEG power would be advantageous for both clinical and research purposes, such as for longitudinal studies measuring changes in sleep stages over time. The purpose of this study was to compare sleep scoring of a single-channel EEG recorded simultaneously on the forehead against attended polysomnography. Participants were recruited from both a clinical sleep centre and a longitudinal research study investigating cognitively normal ageing and Alzheimer's disease. Analysis for overall epoch-by-epoch agreement found strong and substantial agreement between the single-channel EEG compared to polysomnography (kappa = 0.67). Slow wave activity in the frontal regions was also similar when comparing the single-channel EEG device to polysomnography. As expected, Stage N1 showed poor agreement (sensitivity 0.2) due to lack of occipital electrodes. Other sleep parameters, such as sleep latency and rapid eye movement (REM) onset latency, had decreased agreement. Participants with disrupted sleep consolidation, such as from obstructive sleep apnea, also had poor agreement. We suspect that disagreement in sleep parameters between the single-channel EEG and polysomnography is due partially to altered waveform morphology and/or poorer signal quality in the single-channel derivation. Our results show that single channel EEG provides comparable results to polysomnography in assessing REM, combined Stages N2 and N3 sleep and several other parameters, including frontal slow wave activity. The data establish that single-channel EEG can be a useful research tool. PMID- 27252092 TI - Tales of Antigen Evasion from CAR Therapy. AB - Both T cells bearing chimeric antigen receptors and tumor-specific antibodies can successfully target some malignancies, but antigen escape can lead to relapse. Two articles in this issue of Cancer Immunology Research explore what effective countermeasures may prevent it. Cancer Immunol Res; 4(6); 473-473. (c)2016 AACRSee articles by Zah et al., p. 498, and Rufener et al., p. 509. PMID- 27252091 TI - The diagnostic and prognostic value of SALL4 in hepatoblastoma. AB - AIMS: To investigate the expression of spalt-like transcription factor 4 (SALL4), a regulator of embryonal development, in three epithelial components of hepatoblastoma (HB) and the relationship between SALL4 expression levels and patients' clinicopathological features. METHODS AND RESULTS: A total of 115 specimens from 79 patients with HB were selected for immunostaining of SALL4. Nuclear staining was semi-quantified using the immunoreactive score (IS; range: 0 12). SALL4 expression was seen in all embryonal components (mean IS = 8.58) and in 41% of fetal components (mean IS = 0.78). No SALL4 expression was seen in either small cell undifferentiated or mesenchymal components of HB. Neither chemotherapy nor metastasis altered SALL4 expression significantly. High SALL4 expression levels were associated significantly with decreased overall survival (OS) (P = 0.004), event-free survival (EFS) (P = 0.003) and the presence of metastasis (P = 0.049) on univariate analysis. Multivariate analysis identified SALL4 as an independent prognostic predictor for OS (P = 0.029). CONCLUSIONS: SALL4 is useful for subtyping HB, and high SALL4 expression is associated with decreased survival in HB. PMID- 27252093 TI - IMAGING DIAGNOSIS-ENDOMETRIAL MINERALIZATION IN A DOG. AB - A 9-year-old intact female mixed breed dog was presented for mammary gland tumor surgery, and preoperative radiographs showed a tubular soft tissue opacity mass with multifocal mineralization in the caudoventral abdominal cavity. Subsequent ultrasonography demonstrated uterine dilation with echogenic fluid and endometrial acoustic shadowing consistent with mineralization. Resection of mammary gland tumors and ovariohysterectomy were performed. Pyometra was diagnosed on cytologic examination of uterine fluid. Histopathology of the uterine tissue confirmed a diagnosis of cystic endometrial hyperplasia with uterine mineralization. PMID- 27252094 TI - Event-related potentials reveal the development of stable face representations from natural variability. AB - Natural variability between instances of unfamiliar faces can make it difficult to reconcile two images as the same person. Yet for familiar faces, effortless recognition occurs even with considerable variability between images. To explore how stable face representations develop, we employed incidental learning in the form of a face sorting task. In each trial, multiple images of two facial identities were sorted into two corresponding piles. Following the sort, participants showed evidence of having learnt the faces performing more accurately on a matching task with seen than with unseen identities. Furthermore, ventral temporal event-related potentials were more negative in the N250 time range for previously seen than for previously unseen identities. These effects appear to demonstrate some degree of abstraction, rather than simple picture learning, as the neurophysiological and behavioural effects were observed with novel images of the previously seen identities. The results provide evidence of the development of facial representations, allowing a window onto natural mechanisms of face learning. PMID- 27252097 TI - Preparing a Paper for Publication: Help Us Help You Make It Happen. PMID- 27252095 TI - Ontogenetic scaling of fore limb and hind limb joint posture and limb bone cross sectional geometry in vervets and baboons. AB - OBJECTIVES: Previous studies suggest that the postures habitually adopted by an animal influence the mechanical loading of its long bones. Relatively extended limb postures in larger animals should preferentially reduce anteroposterior (A P) relative to mediolateral (M-L) bending of the limb bones and therefore decrease A-P/M-L rigidity. We test this hypothesis by examining growth-related changes in limb bone structure in two primate taxa that differ in ontogenetic patterns of joint posture. MATERIALS AND METHODS: Knee and elbow angles of adult and immature vervets (Chlorocebus aethiops, n = 16) were compared to published data for baboons (Papio hamadryas ursinus, n = 33, Patel et al., ). Ontogenetic changes in ratios of A-P/M-L bending rigidity in the femur and humerus were compared in skeletal samples (C. aethiops, n = 28; P. cynocephalus, n = 39). Size changes were assessed with linear regression, and age group differences tested with ANOVA. RESULTS: Only the knee of baboons shows significant postural change, becoming more extended with age and mass. A-P/M-L bending rigidity of the femur decreases during ontogeny in immature and adult female baboons only. Trends in the humerus are less marked. Adult male baboons have higher A-P/M-L bending rigidity of the femur than females. CONCLUSIONS: The hypothesized relationship between more extended joints and reduced A-P/M-L bending rigidity is supported by our results for immature and adult female baboon hind limbs, and the lack of significant age changes in either parameter in forelimbs and vervets. Adult males of both species depart from general ontogenetic trends, possibly due to socially mediated behavioral differences between sexes. Am J Phys Anthropol 161:72-83, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27252098 TI - Tissue Oxygenation Monitoring as a Guide for Trauma Resuscitation. AB - Hypoperfusion is the most common event preceding the onset of multiple organ dysfunction syndrome during trauma resuscitation. Detecting subtle changes in perfusion is crucial to ensure adequate tissue oxygenation and perfusion. Traditional methods of detecting physiological changes include measurements of blood pressure, heart rate, urine output, serum levels of lactate, mixed venous oxygen saturation, and central venous oxygen saturation. Continuous noninvasive monitoring of tissue oxygen saturation in muscle has the potential to indicate severity of shock, detect occult hypoperfusion, guide resuscitation, and be predictive of the need for interventions to prevent multiple organ dysfunction syndrome. Tissue oxygen saturation is being used in emergency departments, trauma rooms, operating rooms, and emergency medical services. Tissue oxygen saturation technology is just as effective as mixed venous oxygen saturation, central venous oxygen saturation, serum lactate, and Stewart approach with strong ion gap, yet tissue oxygen saturation assessment is also a direct, noninvasive microcirculatory measurement of oxygen saturation. PMID- 27252099 TI - Comparison of Head Elevation Protocols Following Femoral Artery Sheath Removal After Coronary Angiography. AB - OBJECTIVES: To compare 2 standard protocols for head elevation following removal of a femoral artery sheath after coronary angiography and their effects on bleeding complications and reported levels of back pain. One protocol involved flat supine bed rest; the other allowed progressive head elevation. METHODS: A prospective comparative study of 80 adult patients undergoing coronary angiography via the femoral approach. The Numeric Rating Scale was used as the measure of reported pain. RESULTS: No bleeding complications occurred in either group. Both groups had very low mean pain scores. Repeated-measures analysis demonstrated that the experience of pain differed significantly over time by location (F5,70 = 3.864, P = .004), with a notable decrease in pain scores more than 1 hour after sheath removal at the location that used the progressive head elevation protocol. Patients' satisfaction scores after discharge did not differ significantly between the 2 groups. Patients with a history of chronic back pain had consistently higher pain scores, but those pain scores did not differ significantly by location (or protocol). CONCLUSIONS: It appears that using a progressive head-elevation protocol within the first 3 hours after diagnostic angiography is not associated with an increased risk of bleeding complications at the access site and warrants further exploration in the mitigation of back pain associated with prolonged supine bed rest. PMID- 27252100 TI - Hereditary Hemorrhagic Telangiectasia: A Primer for Critical Care Nurses. AB - Hereditary hemorrhagic telangiectasia is a rare, autosomal dominant genetic disease that causes abnormal growth of blood vessels and, subsequently, life threatening arteriovenous malformations in vital organs. Epistaxis may be one of the initial clues that a patient has more serious, generalized arteriovenous malformations. Recommended treatment involves careful evaluation to determine the severity and risk of spontaneous rupture of the malformations and the management of various signs and symptoms. The disease remains undiagnosed in many patients, and health care providers may miss the diagnosis until catastrophic events happen in multiple family members. Prompt recognition of hereditary hemorrhagic telangiectasia and early intervention can halt the dangerous course of the disease. Critical care nurses can assist with early diagnosis within families with this genetic disease, thus preventing early death and disability. PMID- 27252101 TI - Fresh Whole Blood Transfusion: Military and Civilian Implications. AB - Uncontrolled hemorrhage and exsanguination are the leading cause of preventable death, and resuscitative therapy is a critical component for survival. In various combinations, fresh whole blood, blood components, colloids, and crystalloids have all been staples of trauma care. The use of fresh whole blood is a well established military practice that has saved the lives of thousands of American and coalition military personnel. Civilian use of fresh whole blood is far less established owing to the wide availability of individual blood components. However, this highly tailored blood supply is vulnerable to both natural and man made disasters. In the event of such disruption, such as a major hurricane, it may be necessary for civilian hospitals to rapidly enact a fresh whole blood program. Therefore, the aim of this article is to review the current use of blood therapy for trauma resuscitation, the US military's approach to fresh whole blood, and how maintaining a civilian capacity for fresh whole blood collection in the event of future man-made and natural disasters is key to promoting survival from trauma. PMID- 27252103 TI - Critical Care Nurses Cannot "Phone It In". PMID- 27252102 TI - Parent Advocacy Group for Events of Resuscitation. AB - BACKGROUND: The presence of patients' families during resuscitation has been an important practice issue. An American Association of Critical-Care Nurses (AACN) practice alert "Family Presence During Resuscitation and Invasive Procedures" supports family members of patients undergoing resuscitation being given the option of bedside presence. Parent Advocacy Group for Events of Resuscitation (PAGER) is an interdisciplinary collaborative in the pediatric intensive care unit. OBJECTIVES: To ensure that patients' families are provided the option of being with their child during cardiopulmonary resuscitation. METHODS: Resuscitation data were collected for 12 months by using the AACN practice alert audit tool. The Family Nurse Caring Belief Scale was administered to 150 pediatric intensive care unit nurses. PAGER nurses received crisis education. RESULTS: Pediatric intensive care unit nurses were supportive of providing the option of family presence during resuscitation. Family Nurse Caring Belief Scale data revealed areas for improvement in family caring practices. PAGER was implemented with positive outcomes for 2 families. CONCLUSIONS: PAGER has improved the care of families whose children experience cardiopulmonary resuscitation and should be implemented in pediatric critical care units. PAGER nurses are prepared to serve as role models in providing family-sensitive care during crisis. PMID- 27252104 TI - Best Practices in Caring for Patients Infected With Clostridium difficile. PMID- 27252105 TI - I Am a Critical Care Nurse. PMID- 27252106 TI - Acute Disseminated Encephalomyelitis After Influenza Vaccination: A Case Report. AB - Acute disseminated encephalomyelitis is an inflammatory demyelinating disease of the central nervous system that has been associated with influenza immunization, but only a few cases related to vaccination for influenza have been reported. Acute disseminated encephalomyelitis developed in a 42-year-old woman within 3 weeks of receiving the seasonal influenza vaccine. She had 80% recovery after 3 months of treatment with methylprednisolone. Although cases of acute disseminated encephalomyelitis after vaccination for influenza are rare, enough of them have occurred that critical care nurses should be aware of the possibility. Early treatment can prevent serious residual signs and symptoms; therefore, correct and quick diagnosis is important. Medical history obtained from patients with central nervous system problems should include history of recent vaccinations. PMID- 27252107 TI - Obtaining Accurate Noninvasive Blood Pressure Measurements in Adults. PMID- 27252108 TI - Solid-Organ Graft-Versus-Host Disease After Liver Transplant: A Case Report. AB - Solid-organ transplant graft-versus-host disease (SOT-GVHD) is a rare complication of organ transplant that is associated with high mortality. The initial signs and symptoms are vague, so this disease is easily confused with other posttransplant complications. A case of SOT-GVHD occurred after orthotopic liver transplant for liver failure due to hepatitis C in a patient in a Veterans Affairs intensive care unit. The patient had dehydration, acute kidney injuries, rashes, diarrhea, and pancytopenia. Results of skin biopsy, bone marrow biopsy, and cytogenetic studies were consistent with SOT-GVHD. Despite supportive care including antibiotics, antiviral and antifungal therapy, high-dose steroids, antithymoglobulin and neupogen, the patient died of overwhelming sepsis. Owing to the rarity of SOT-GVHD, no evidence-based guidelines or recommendations for treatment exist. Treatment includes high-dose corticosteroids and antibiotic, antifungal, and antiviral prophylaxis. Treatment of liver transplant-related GVHD with anti-tumor necrosis factor a agents has been successful. PMID- 27252109 TI - Lipopeptides from a novel Bacillus methylotrophicus 39b strain suppress Agrobacterium crown gall tumours on tomato plants. AB - BACKGROUND: This study aims to characterise the antibacterial activity of a novel Bacillus methylotrophicus strain named 39b against tumourigenic Agrobacterium tumefaciens C58 and B6 strains. It also aims to identify the compound that is responsible for its activity and to evaluate its efficiency to control crown gall disease in tomato plants. RESULTS: B. methylotrophicus strain 39b was found to stop the growth of phytopathogenic A. tumefaciens strains in in vitro experiments. Lipopeptides - surfactins, iturins and fengycins - were detected under various isoforms by mass spectrometry analysis of the methanolic extract. The active principle acting against Agrobacterium strains was isolated from TLC plates and identified by mass spectrometry as surfactin. The strain was effective in reducing the weight and the number of galls induced by A. tumefaciens strains on tomato plants. Total inhibition of gall formation was observed using the antibacterial compounds. CONCLUSION: B. methylotrophicus strain 39b exhibited antibacterial activity against phytopathogenic A. tumefaciens C58 and B6 both in vitro and in vivo. Lipopeptides are the main compounds that confer the biocontrol ability. This strain has the potential to be developed as a biological control agent for crown gall disease. (c) 2016 Society of Chemical Industry. PMID- 27252110 TI - Risk Factors and Utility of a Risk-Based Algorithm for Monitoring Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections in Pediatric Recipients after Allogeneic Hematopoietic Cell Transplantation. AB - Infectious complications, particularly viral infections, remain a significant cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (alloHCT). Only a handful of studies in children have analyzed the risks for and impact of viremia on alloHCT-related outcomes. We conducted a retrospective study of 140 pediatric patients undergoing alloHCT to investigate the incidence of and risk factors for cytomegalovirus (CMV), adenovirus (ADV), and Epstein-Barr virus (EBV) viremia and viral disease after alloHCT. Furthermore, we assessed the impact of viremia on days of hospitalization and develop an algorithm for routine monitoring of viremia. Patients were monitored before alloHCT and then weekly for 180 days after alloHCT. Patients were considered to have viremia if CMV were > 600 copies/mL, EBV were > 1000 copies/mL, or ADV were > 1000 copies/mL on 2 consecutive PCRs. The overall incidences of viremia and viral disease in all patients from day 0 to +180 after alloHCT were 41.4% (n = 58) and 17% (n = 24), respectively. The overall survival for patients with viremia and viral disease was significantly lower compared with those without viremia (58% versus 74.2%, P = .03) and viral disease (48.2% versus 71.2%, P = .024). We identified that pretransplantation CMV risk status, pre alloHCT viremia, and use of alemtuzumab were associated with the risk of post alloHCT viremia. The average hospitalization days in patients with CMV risk (P = .011), viremia (P = .024), and viral disease (P = .002) were significantly higher. The algorithm developed from our data can potentially reduce viral PCR testing by 50% and is being studied prospectively at our center. Improved preventative treatment strategies for children at risk of viremia after alloHCT are needed. PMID- 27252111 TI - Ameliorative Effect of Quercetin on Neurochemical and Behavioral Deficits in Rotenone Rat Model of Parkinson's Disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease). AB - Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death. PMID- 27252113 TI - Land-use contrasts reveal instability of subsoil organic carbon. AB - Subsoils contain large amounts of organic carbon which is generally believed to be highly stable when compared with surface soils. We investigated subsurface organic carbon storage and dynamics by analysing organic carbon concentrations, fractions and isotopic values in 78 samples from 12 sites under different land uses and climates in eastern Australia. Despite radiocarbon ages of several millennia in subsoils, contrasting native systems with agriculturally managed systems revealed that subsurface organic carbon is reactive on decadal timeframes to land-use change, which leads to large losses of young carbon down the entire soil profile. Our results indicate that organic carbon storage in soils is input driven down the whole profile, challenging the concept of subsoils as a repository of stable organic carbon. PMID- 27252114 TI - Hidden Nanobubbles in Undersaturated Liquids. AB - Here, we propose theoretically the existence of a new type of nanobubble in undersaturated liquids. These nanobubbles have a concave vapor-liquid interface featured with a negative curvature rather than a positive curvature for nanobubbles in supersaturated liquids, so that they often hide inside of the substrate textures and it might not be easy to characterize them through atomic force microscopy (AFM) measurements. However, these hidden nanobubbles are still stabilized by the contact line pinning effect and stay at the thermodynamically metastable state. We further demonstrate that similar to the nanobubbles in supersaturated liquids the contact angle of the hidden nanobubbles is more sensitive to the nanobubble size rather than the substrate chemistry, and their curvature radius is dependent on the chemical potential but independent of the base radius. Finally, we show several potential situations for the appearance of the hidden nanobubbles. PMID- 27252112 TI - Defense pattern of Chinese cork oak across latitudinal gradients: influences of ontogeny, herbivory, climate and soil nutrients. AB - Knowledge of latitudinal patterns in plant defense and herbivory is crucial for understanding the mechanisms that govern ecosystem functioning and for predicting their responses to climate change. Using a widely distributed species in East Asia, Quercus variabilis, we aim to reveal defense patterns of trees with respect to ontogeny along latitudinal gradients. Six leaf chemical (total phenolics and total condensed tannin concentrations) and physical (cellulose, hemicellulose, lignin and dry mass concentration) defensive traits as well as leaf herbivory (% leaf area loss) were investigated in natural Chinese cork oak (Q. variabilis) forests across two ontogenetic stages (juvenile and mature trees) along a ~14 degrees -latitudinal gradient. Our results showed that juveniles had higher herbivory values and a higher concentration of leaf chemical defense substances compared with mature trees across the latitudinal gradient. In addition, chemical defense and herbivory in both ontogenetic stages decreased with increasing latitude, which supports the latitudinal herbivory-defense hypothesis and optimal defense theory. The identified trade-offs between chemical and physical defense were primarily determined by environmental variation associated with the latitudinal gradient, with the climatic factors (annual precipitation, minimum temperature of the coldest month) largely contributing to the latitudinal defense pattern in both juvenile and mature oak trees. PMID- 27252115 TI - The role and significance of endomorphin-1 and MU-opioid receptor in rats with endometriosis. AB - Endomorphin-1 (EM-1) was reported to have very high affinity and selectivity for MU-opioid receptor (MOR). However, it remained unclear whether EM-1 and MOR were involved in the pathologies of endometriosis resulting in reduced fertility. In this study, RT-PCR, radioimmunoassay, immunohistochemistry, and Western blot were used, respectively. The results showed that the immune positive cells of EM-1 in hypothalamus, pituitary, and ovaries were significantly increased in endometriosis model rats, accompanied by the increase of plasma level of EM-1 and the decrease of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P). Interestingly, EM-1 was negatively correlated with FSH and LH (p < 0.05). More importantly, Naloxone (MOR antagonist) can significantly reduce the levels of EM-1 in serum, hypothalamus, pituitary, and ovaries, while increased the levels of FSH and LH. In conclusion, our results suggested that EM-1 may be involved in the pathogenesis of the endometriosis-associated infertility by regulating hypothalamus-pituitary-ovarian axis, and Naloxone may be a new alternative drug for the treatment of endometriosis. PMID- 27252116 TI - Characteristics and outcomes of lymphoblastic lymphoma - the University of Miami experience. PMID- 27252117 TI - The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice. AB - CONTEXT: Acetaminophen overdose is regarded to a common cause of acute liver failure. The hepatotoxicity leads to mitochondrial oxidative stress and subsequent necrotic hepatocellular death. OBJECTIVE: This study examines the protective effect of metformin on acetaminophen-induced oxidative stress, inflammation and subsequent hepatotoxicity in mice. MATERIALS AND METHODS: Male BALB/c mice were orally administered to acetaminophen (250 mg/kg/d) for a 7-day period. The mice received metformin (100 and 200 mg/kg/d, p.o.) for 21 days. To evaluate acetaminophen-induced oxidative stress, liver tissue level of malodialdehyde (MDA), end product of membrane lipid peroxidation, and activities of superoxide dismutase (SOD) and glutathione (GSH) were measured. Histological analysis and measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were performed. Moreover, tissue concentrations of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), along with, C-reactive protein (CRP) were assessed. RESULTS: Acetaminophen caused focal hepatocyte necrosis, inflammation and fatty degeneration, as well as increased tissue levels of AST, ALT, ALP and MDA, and also decreased GSH and SOD activities. Moreover, IL-6, TNF-alpha and CRP levels were increased following acetaminophen hepatotoxicity. Metformin (200 mg/kg/d) significantly normalized MDA, SOD and GSH levels (p < 0.001), and exerted a hepatoprotective effect by significant decreasing ALT, AST and ALP concentrations (p < 0.001). The tissue levels of IL-6, TNF-alpha and CRP were markedly decreased by 21-day treatment with metformin (200 mg/kg/d) (p < 0.001). DISCUSSION: The results suggest metformin protects hepatocytes against acute acetaminophen toxicity. Metformin is indicated to diminish oxidative stress, proinflammatory cytokines, and hepatocyte necrosis. PMID- 27252118 TI - Conjugated Polymer-Based Hybrid Materials for Turn-On Detection of CO2 in Plant Photosynthesis. AB - Detection of carbon dioxide (CO2) is of fundamental importance in diverse applications ranging from environmental analysis to agricultural production. In this work, a hybrid probe based on guanidinium-pendent oligofluorene (G-OF) and water-soluble conjugated polythiophene (PTP) has been developed for the turn on detection of CO2 with low background signal, taking advantage of the efficient fluorescence quenching of the tight aggregate of G-OF/PTP. In the presence of CO2, the electrostatic repulsion between G-OF and PTP can be effectively enhanced through protonation of the side chains, leading to the disaggregation and thus the "turn-on" fluorescence. The strategy allows for the light-up visible detection of CO2 with high sensitivity. Importantly, this system is capable of sensitively monitoring the concentration changes of CO2 in the process of the photosynthesis, which represents a concept to monitor the photosynthesis based on water-soluble conjugated polymers. PMID- 27252119 TI - Prognostic significance of hematological profiles in melanoma patients. AB - Cancer-related inflammation may play an important role in disease progression and patient outcome, and could be easily monitored through indirect parameters routinely evaluated at diagnosis. Here, we investigated if peripheral blood cells and the ratios of neutrophils to lymphocytes (NLR) and of lymphocytes to monocytes (LMR) as surrogate markers of cancer related inflammation are associated with disease progression and survival of melanoma patients at any stage of the disease. Records of 1,182 melanoma patients included in an Institutional tumor registry in the period 2000-2010, were reviewed. Among them, 584 patients with a cutaneous or unknown primary melanoma and available pre operative blood tests were analyzed. Survival was estimated with the Kaplan-Meier method, and analyzed using Log-rank test, Cox regression and multivariate Cox proportional hazard models. We found that patients presenting with distant metastases had higher leukocytes, neutrophils and monocytes, and lower lymphocytes compared to Stage I-III patients. Furthermore, at a single-patient level, hematological profiles changed on disease progression from regional to distant metastatic, with significantly increased circulating leukocytes, neutrophils and monocytes, and decreased lymphocytes. Peripheral blood cell counts were not associated with survival of patients with a localized or regionally metastasized melanoma. Instead, in Stage IV patients, leukocytes (p = 0.001), neutrophils (p = 0.0002), monocytes (p = 0.002), NLR (p < 0.0001) and LMR (p = 0.005) were all significantly associated with survival, independently of other known prognostic factors. These results suggest that cellular components of peripheral blood do count for survival of patients with advanced melanoma. PMID- 27252120 TI - Backfilling-Free Strategy for Biopatterning on Intrinsically Dual-Functionalized Poly[2-Aminoethyl Methacrylate-co-Oligo(Ethylene Glycol) Methacrylate] Films. AB - We demonstrated protein and cellular patterning with a soft lithography technique using poly[2-aminoethyl methacrylate-co-oligo(ethylene glycol) methacrylate] films on gold surfaces without employing a backfilling process. The backfilling process plays an important role in successfully generating biopatterns; however, it has potential disadvantages in several interesting research and technical applications. To overcome the issue, a copolymer system having highly reactive functional groups and bioinert properties was introduced through a surface initiated controlled radical polymerization with 2-aminoethyl methacrylate hydrochloride (AMA) and oligo(ethylene glycol) methacrylate (OEGMA). The prepared poly(AMA-co-OEGMA) film was fully characterized, and among the films having different thicknesses, the 35 nm-thick biotinylated, poly(AMA-co-OEGMA) film exhibited an optimum performance, such as the lowest nonspecific adsorption and the highest specific binding capability toward proteins. PMID- 27252121 TI - High performance CCD camera system for digitalisation of 2D DIGE gels. AB - An essential step in 2D DIGE-based analysis of differential proteome profiles is the accurate and sensitive digitalisation of 2D DIGE gels. The performance progress of commercially available charge-coupled device (CCD) camera-based systems combined with light emitting diodes (LED) opens up a new possibility for this type of digitalisation. Here, we assessed the performance of a CCD camera system (Intas Advanced 2D Imager) as alternative to a traditionally employed, high-end laser scanner system (Typhoon 9400) for digitalisation of differential protein profiles from three different environmental bacteria. Overall, the performance of the CCD camera system was comparable to the laser scanner, as evident from very similar protein abundance changes (irrespective of spot position and volume), as well as from linear range and limit of detection. PMID- 27252123 TI - Amphiphilic calixresorcinarene associates as effective solubilizing agents for hydrophobic organic acids: construction of nano-aggregates. AB - Here we represent the first example of the formation of mixed nanoscale associates, constructed from amphiphilic calixresorcinarenes and hydrophobic carboxylic acids including drugs. The amidoamino-calixresorcinarene self associates effectively solubilize hydrophobic carboxylic acids - drugs such as naproxen, ibuprofen, ursodeoxycholic acid and aliphatic dodecanoic acid - with the formation of the mixed aggregates with the macrocycle/substrate stoichiometry from 1/1 to 1/7. The ionization of organic acids and the peripheral nitrogen atoms of the macrocycles with the subsequent inclusion of hydrophobic acids into the macrocycle self-associates is the driving force of solubilization. In some cases, this leads to the co-assembly of the macrocycle polydisperse associates into supramolecular monodisperse nanoparticles with the diameter of about 100 nm. The efficiency of drug loading into the nanoparticles is up to 45% and depends on the structure of organic acid. The dissociation of the mixed aggregates and release of organic acid are attained by decreasing pH. PMID- 27252122 TI - R-loop: an emerging regulator of chromatin dynamics. AB - The dynamic structure of chromatin, which exists in two conformational states: heterochromatin and euchromatin, alters the accessibility of the DNA to regulatory factors during transcription, replication, recombination, and DNA damage repair. Chemical modifications of histones and DNA, as well as adenosine triphospahate-dependent nucleosome remodeling, have been the major focus of research on chromatin dynamics over the past two decades. However, recent studies using a DNA-RNA hybrid-specific antibody and next-generation sequencing approaches have revealed that the formation of R-loops, one of the most common non-canonical DNA structures, is an emerging regulator of chromatin states. This review focuses on recent insights into the interplay between R-loop formation and the epigenetic modifications of chromatin in normal and disease states. PMID- 27252124 TI - Post-exposure antiviral treatment of norovirus infections effectively protects against diarrhea and reduces virus shedding in the stool in a mortality mouse model. AB - Noroviruses are a leading cause of gastroenteritis across the world in all age groups and are linked to increased hospitalization and mortality in children, the elderly and immunocompromised. The development of specific antiviral treatment for norovirus gastroenteritis is urgently needed. We explored in a mouse model whether an inhibitor of norovirus replication could be used therapeutically post murine norovirus (MNV)-infection of mice. Using the MNV, we previously discovered that the viral polymerase inhibitor 2'-C-methylcytidine (2CMC) is able to protect against diarrhea and mortality in mice when used prophylactically and to block the transmission of MNV between mice. Here, we investigated whether 2CMC could be used therapeutically, starting treatment between 12 h and 3 days post-infection with 2CMC. Post-exposure treatment of MNV-infected mice with 2CMC was efficient up to 2 days after infection, preventing norovirus-induced diarrhea, delaying and reducing MNV shedding in stool of treated mice. Rehydration of 2CMC-treated animals did not result in a further improvement of the disease evolution compared to antiviral treatment only. The presence of MNV antigens and inflammation in the small intestine of infected mice inversely correlated with the effectiveness of delayed antiviral treatment. Anti-MNV IgGs were detected in re-challenged mice 10 weeks after the first contact, these protected the mice from re-infection. We here demonstrate the benefit of antiviral treatment in ongoing norovirus infections. PMID- 27252125 TI - Backpack palsy: A rare complication of backpack use in children and young adults A new case report. AB - Backpack palsy is a well-recognised, albeit rare, complication of carrying backpacks. Although it has been mostly described in cadets during strenuous training, sporadic cases of brachial nerve impairment have been reported in children and young adults. Here we reported the case of a 15-year-old girl who presented with a left-side brachial palsy with axonal denervation of C5C7 motor roots following a school challenge for the Duke of Edinburgh Award. Her symptoms began soon after starting the challenge and included weakness of shoulder abduction and elevation, as well as forearm, wrist and fingers extension. After 6 months of physiotherapy her motor function was completely restored. Backpack palsy can sometimes present in children and young adults. This disorder should be taken in consideration when planning for daily, as well as more challenging, physical activities in these age groups. PMID- 27252127 TI - Associations Between Substance Use in Commission of Sexual Crimes and Offense Characteristics Among Youth: Mitigating Effects of Substance Use Treatment. AB - The small extant research base on substance use and youth sexual offending has very few descriptive details. Furthermore, research has yet to test associations between the use of substances in the commission of sexual crimes and offense related characteristics and how substance use treatment can mitigate these effects. In a sample of residentially housed youth adjudicated of a sexual crime ( N = 332), prevalence patterns are broken down by type of substance use behavior. Sequential regression models are run to test the associations between substance use prior to a sexual crime and number of victims, sexual deviance, and non-sexual criminality. Substance use treatment is tested as a mitigating factor in these relationships. Results reveal high levels of family substance use, and high rates of alcohol, marijuana, and other substance use. There were associations between substance use prior to sexual criminality and sexual deviance and non-sexual criminality. Substance use treatment reduced the effects of substance use on non-sexual criminality. Research and treatment implications are offered. PMID- 27252126 TI - Adverse reaction after hyaluronan injection for minimally invasive papilla volume augmentation. A report on two cases. AB - OBJECTIVES: To report two cases of adverse reaction after mucosal hyaluronan (HY) injection around implant-supported crowns, with the aim to augment the missing interdental papilla. MATERIAL AND METHODS: Two patients with single, non neighbouring, implants in the anterior maxilla, who were treated within the frames of a randomized controlled clinical trial testing the effectiveness of HY gel injection to reconstruct missing papilla volume at single implants, presented an adverse reaction. Injection of HY was performed bilaterally using a 3-step technique: (i) creation of a reservoir in the mucosa directly above the mucogingival junction, (ii) injection into the attached gingiva/mucosa below the missing papilla, and (iii) injection 2-3 mm apically to the papilla tip. The whole-injection session was repeated once after approximately 4 weeks. RESULTS: Both patients presented with swelling and extreme tenderness with a burning sensation on the lip next to the injection area, after the second injection session. In one of the cases, a net-like skin discoloration (livedo reticularis) was also noted. The symptoms lasted for up to 7 days, and in both cases, symptoms resolved without any signs of skin or mucosal necrosis or any permanent damage. CONCLUSION: Most likely, water attraction over time by the highly hygroscopic HY, exerted progressively an external vascular compression and at least partial occlusion of neighbouring blood vessels. An infection or an allergic reaction seems unlikely, since all symptoms gradually disappeared within a week irrespective use of antimicrobials, while an allergic reaction most likely would not have been restricted to one side. PMID- 27252129 TI - Winning at Go: The Conundrum of Computational Mind. PMID- 27252128 TI - Advances in electroanalysis, sensing and monitoring in molten salts. AB - Microelectrodes have a number of advantages over macroelectrodes for quantitative electroanalysis and monitoring, including reduced iR drop, a high signal-to-noise ratio and reduced sensitivity to convection. Their use in molten salts has been generally precluded by the combined materials challenges of stresses associated with thermal cycling and physical and corrosive chemical degradation at the relatively high temperatures involved. We have shown that microfabrication, employing high precision photolithographic patterning in combination with the controlled deposition of materials, can be used to successfully address these challenges. The resulting molten salt compatible microelectrodes (MSMs) enable prolonged quantitative microelectrode measurements in molten salts (MSs). This paper reports the fabrication of novel MSM disc electrodes, chosen because they have an established ambient analytical response. It includes a detailed set of electrochemical characterisation studies which demonstrate both their enhanced capability over macroelectrodes and over commercial glass pulled microelectrodes, and their ability to extract quantitative electroanalytical information from MS systems. MSM measurements are then used to demonstrate their potential for shedding new light on the fundamental properties of, and processes in, MSs, such as mass transport, charge transfer reaction rates and the selective plating/stripping and alloying reactions of liquid Bi and other metals; this will underpin the development of enhanced MS industrial processes, including pyrochemical spent nuclear fuel reprocessing. PMID- 27252131 TI - Erratum. PMID- 27252130 TI - Talin: a mechanosensitive molecule in health and disease. AB - Talin is a ubiquitous, large focal adhesion protein that links intracellular networks with the extracellular matrix (ECM) via its connection with the actin cytoskeleton and membrane integrins. It is one of a handful molecules that can expose new recognition sites when undergoing force-induced mechanical unfolding, and it can bind and recruit cytoskeletal proteins that are involved in mechanotransduction. Talin has attracted great interest in the field of mechanobiology because of its plasticity in undergoing conformational changes under force stimulation as well as its cellular localization that bridges the cytoskeleton with the ECM. In addition to these roles in healthy cells, the dysregulation of talin activators can lead to disease states in which aberrant integrin activation and mechanotransduction precipitate changes in cell spreading, migration, and survival. New data have implicated a role for talin in diseases that are highly regulated by mechanical cues. In this review, we present the current understanding of talin structure, its relationship to binding partners, and its role in disease states.-Haining, A. W. M., Lieberthal, T. J., del Rio Hernandez, A. Talin: a mechanosensitive molecule in health and disease. PMID- 27252132 TI - Reporting postoperative morbidity and mortality by hospital and surgeon: a new era in accountability. PMID- 27252133 TI - Evolution of the Bi-National Colorectal Cancer Audit: history, governance and future directions. PMID- 27252134 TI - The 2015 Asia Pacific Federation of Coloproctogy Congress: bringing colorectal surgeons and stomal therapists together to the world's most liveable city. PMID- 27252135 TI - Medicine in small doses. PMID- 27252136 TI - 25, 50 & 75 years ago. PMID- 27252137 TI - Publons.com: credit where credit is due. PMID- 27252138 TI - Response to Re: No weak days? Impact of day in the week on surgical mortality. PMID- 27252139 TI - Re: No weak days? Impact of day in the week on surgical mortality. PMID- 27252140 TI - Folded superficial temporal artery flap for repair of penetrated nasal defects. PMID- 27252141 TI - Ectopic liver, choristoma and hepar succenturiatum. PMID- 27252142 TI - Re: Surgical dilemma: loss of open surgical skills to minimally invasive surgery. PMID- 27252143 TI - The Spirit and Intent of Motivational Interviewing. AB - PURPOSE: To describe an educational program to improve inpatient psychiatric nursing staff communication skills to better provide patient-centered care throughout patient hospitalization. DESIGN AND METHODS: Delivered and evaluated an educational program to increase inpatient staff knowledge and use of communication skills during patient encounters. CONCLUSIONS: Emphasizing the spirit and intent of motivational interviewing in a training program results in a translation of the newly obtained knowledge into nursing practice, as evidenced by observed use of motivational interviewing skills during which patient encounters to strengthen the therapeutic alliance. PRACTICE IMPLICATIONS: Advanced Psychiatric Nurse Practitioners can provide an important role of coaching/mentorship for inpatient psychiatric nursing staff to further develop communication skills that are meaningful, patient-centered, and may lead to improved treatment adherence. PMID- 27252145 TI - Corrigendum. PMID- 27252144 TI - Development of nap neurophysiology: preliminary insights into sleep regulation in early childhood. AB - Although all young children nap, the neurophysiological features and associated developmental trajectories of daytime sleep remain largely unknown. Longitudinal studies of napping physiology are fundamental to understanding sleep regulation during early childhood, a sensitive period in brain and behaviour development and a time when children transition from a biphasic to a monophasic sleep-wakefulness pattern. We investigated daytime sleep in eight healthy children with sleep electroencephalography (EEG) assessments at three longitudinal points: 2 years (2.5-3.0 years), 3 years (3.5-4.0 years) and 5 years (5.5-6.0 years). At each age, we measured nap EEG during three randomized conditions: after 4 h (morning nap), 7 h (afternoon nap) and 10 h (evening nap) duration of prior wakefulness. Developmental changes in sleep were most prevalent in the afternoon nap (e.g. decrease in sleep duration by 30 min from 2 to 3 years and by 20 min from 3 to 5 years). In contrast, nap sleep architecture (% of sleep stages) remained unchanged across age. Maturational changes in non-rapid eye movement sleep EEG power were pronounced in the slow wave activity (SWA, 0.75-4.5 Hz), theta (4.75 7.75 Hz) and sigma (10-15 Hz) frequency ranges. These findings indicate that the primary marker of sleep depth, SWA, is less apparent in daytime naps as children mature. Moreover, our fundamental data provide insight into associations between sleep regulation and functional modifications in the central nervous system during early childhood. PMID- 27252147 TI - From natural to biomimetic: The superhydrophobicity and the contact time. AB - The superhydrophobicities and the contact time of lotus leaf and reed leaf were investigated. The results indicated that both lotus leaf and reed leaf have good superhydrophobic properties, and the water contact time was 12.7 and 14.7 ms on the surface of lotus leaf and reed leaf, respectively. Surface structure plays a key role in the different contacting times. Homogeneous distribution of papillae on the surface of lotus leaf was more helpful to reduce the contact time than anisotropic groove-shape on the surface of reed leaf. Based on the bionics coupling theory, the bionics sample possessing similar lotus-leaf-like surface structure on the aluminum alloy was designed and fabricated successfully. The water contact angle was about 153 +/- 2 degrees , sliding angle less than 5 degrees , and the water contact time was 13.4 ms on the surface of bionics sample, which presented excellent superhydrophobic property, and achieved the aim of bionic design. Microsc. Res. Tech. 79:712-720, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27252148 TI - Interactive effects of temperature and drought on cassava growth and toxicity: implications for food security? AB - Cassava is an important dietary component for over 1 billion people, and its ability to yield under drought has led to it being promoted as an important crop for food security under climate change. Despite its known photosynthetic plasticity in response to temperature, little is known about how temperature affects plant toxicity or about interactions between temperature and drought, which is important because cassava tissues contain high levels of toxic cyanogenic glucosides, a major health and food safety concern. In a controlled glasshouse experiment, plants were grown at 2 daytime temperatures (23 degrees C and 34 degrees C), and either well-watered or subject to a 1 month drought prior to harvest at 6 months. The objective was to determine the separate and interactive effects of temperature and drought on growth and toxicity. Both temperature and drought affected cassava physiology and chemistry. While temperature alone drove differences in plant height and above-ground biomass, drought and temperature * drought interactions most affected tuber yield, as well as foliar and tuber chemistry, including C : N, nitrogen and cyanide potential (CNp; total cyanide released from cyanogenic glucosides). Conditions that most stimulated growth and yield (well-watered * high temperature) effected a reduction in tuber toxicity, whereas drought inhibited growth and yield, and was associated with increased foliar and tuber toxicity. The magnitude of drought effects on tuber yield and toxicity were greater at high temperature; thus, increases in tuber CNp were not merely a consequence of reduced tuber biomass. Findings confirm that cassava is adaptable to forecast temperature increases, particularly in areas of adequate or increasing rainfall; however, in regions forecast for increased incidence of drought, the effects of drought on both food quality (tuber toxicity) and yield are a greater threat to future food security and indicate an increasing necessity for processing of cassava to reduce toxicity. PMID- 27252149 TI - Treatment of kaposiform hemangioendothelioma and tufted angioma. AB - This meta-analysis was to evaluate the efficacy of current treatment modalities for kaposiform hemangioendothelioma and tufted angioma. A systematic review was performed using PubMed (Medline), Web of Science and Embase for clinical studies. The outcome was measured by pooled response rate with 95% confidence intervals (CIs), together with heterogeneity, subgroup analysis, sensitivity analysis and publication bias. Fifteen studies with 244 participants were included in this analysis. Vincristine therapy exhibited a relatively higher response rate (0.72; 95%CI, 0.64-0.79) compared with other therapies including systemic corticosteroid (0.27; 95%CI, 0.17-0.36), interferon (0.36; 95%CI, 0.24-0.48), radiotherapy (0.49; 95%CI, 0.26-0.73), embolization (0.66; 95%CI, 0.48-0.83), aspirin/ticlopidine (0.42; 95%CI, 0.06-0.78) and sirolimus (0.57; 95%CI, 0.00 0.10), in treating KHE/TA. Subgroup analysis indicated that the efficacy of systemic corticosteroids therapy was age-related. The pooled response rate was 0.15 (95%CI, 0.08-0.23) for participants 3.5 months of age and older compared with 0.35 (95% CI, 0.26-0.44) for participants less than 3.5 months. Regarding side effects, systemic corticosteroids treatment was 0.32 (95%CI, 0.15-0.50), vincristine modality was 0.16 (95%CI, 0.08-0.24) and interferon therapy was 0.28 (95%CI, 0.13-0.43). In conclusion, as one of the first reviews evaluating the effect of common therapies in the treatment of KHE/TA, our meta-analysis displayed that vincristine was more effective. Thus, vincristine was the most effective, providing evidence supporting the use of vincristine as a first-line therapy for KHE/TA. PMID- 27252151 TI - Biocomposite macroporous cryogels as potential carrier scaffolds for bone active agents augmenting bone regeneration. AB - Osteoinduction can be enhanced by combining scaffolds with bone morphogenic protein-2 (BMP-2). However, BMP's are known to also cause bone resorption. This can be controlled using bisphosphonates like zoledronic acid (ZA). In this study, we produced two different scaffolds containing silk-fibroin, chitosan, agarose and hydroxyapatite (HA) with and without bioactive glass. The aims of the study were to fabricate, physico-chemically characterize and evaluate the carrier properties of the scaffolds for recombinant human BMP-2 (rhBMP-2) and ZA. Scaffolds were characterized using various methods to confirm their composition. During cell-material interactions, both scaffolds exhibited gradual but sustained proliferation of both C2C12 and MSCs for a period of 6weeks with augmentative effects on their phenotype indicated by elevated levels of alkaline phosphatase (ALP) cuing towards osteogenic differentiation. In-vitro effects of rhBMP-2 and ZA contained within both the scaffolds was assessed on MC3T3 preosteoblast cells and the results show a significant increase in the ALP activity of the cells seeded on scaffolds with rhBMP-2. Further, the scaffold with both HA and bioactive glass was considered for the animal study. In-vitro, this scaffold released nearly 25% rhBMP-2 in 21-days and the addition of ZA did not affect the release. In the animal study, the scaffolds were combined with rhBMP-2 and ZA, rhBMP-2 or implanted alone in an ectopic muscle pouch model. Significantly higher bone formation was observed in the scaffold loaded with both rhBMP-2 and ZA as seen from micro-computed tomography, histomorphometry and energy dispersive X-ray spectroscopy. PMID- 27252150 TI - Prognostic value of health-related quality of life for death risk stratification in patients with unresectable glioblastoma. AB - Glioblastoma is the most common malignant brain tumor in adults. Baseline health related quality of life (HRQoL) is a major subject of concern for these patients. We aimed to assess the independent prognostic value of HRQoL in unresectable glioblastoma (UGB) patients for death risk stratification. One hundred and thirty four patients with UGB were enrolled from the TEMAVIR trial. HRQoL was evaluated at baseline using the EORTC QLQ-C30 and BN20 brain cancer module. Clinical and HRQoL parameters were evaluated in univariable and multivariable Cox analysis as prognostic factors for overall survival (OS). Performance assessment and internal validation of the final model were evaluated with Harrel's C-index, calibration plot, and bootstrap sample procedure. Two OS independent predictors were identified: future uncertainty and sensitivity deficit. The final model exhibited good calibration and acceptable discrimination (C statistic = 0.63). The internal validity of the model was verified with robust uncertainties around the hazard ratio. The prognostic score identified three groups of patients with distinctly different risk profiles with median OS estimated at 16.2, 9.2, and 4.5 months. We demonstrated the additional prognostic value of HRQoL in UGB for death risk stratification and provided a score that may help to guide clinical management and stratification in future clinical trials. PMID- 27252153 TI - Strong hydrophobic interaction between graphene oxide and supported lipid bilayers revealed by AFM. AB - Understanding the interaction between graphene oxide (GO) and lipid membranes is of great importance for its various applications in biotechnology. Here, we investigated the interaction between GO and charged supported lipid bilayers (SLBs) by in situ atomic force microscope (AFM) imaging. It was found that GO could peel off a single layer of positively charged SLBs and deposited on the hydrophobic part of the remaining sublayer. Then free lipid molecules would assemble on GO surface and formed 1.5 bilayers in a lipid-GO-lipid manner. For negatively charged lipid bilayers, however, GO deposited to the SLBs only when its concentration was very high. These results indicate that, in addition to electrostatic interaction, the hydrophobic interaction plays an important role when GO sheets deposit onto the charged lipid bilayers, and should be helpful to understand possible cytotoxicity and antibiosis of graphene-related nanomaterials. Microsc. Res. Tech. 79:721-726, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27252152 TI - Blood mercury levels and fish consumption in pregnancy: Risks and benefits for birth outcomes in a prospective observational birth cohort. AB - BACKGROUND: To avoid exposure to mercury, government advice on fish consumption during pregnancy includes information on fish species to avoid and to limit, while encouraging consumption of least two portions of fish per week. Some women may, however, chose to avoid fish completely during pregnancy despite potential benefits to the fetus. OBJECTIVES: Our aims were to evaluate the effects of blood mercury levels in pregnant women on birth outcomes in the UK, and to compare outcomes in those who ate fish with those who did not. METHODS: Pregnant women were enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Whole blood samples for singleton pregnancies with a live birth were analysed for Hg by inductively coupled plasma dynamic reaction cell mass spectrometry (n=4044). Fish intake was determined by a food frequency questionnaire during pregnancy. Data collected on the infants included anthropometric variables and gestational age at delivery. Regression models were adjusted for covariates using SPSS v23. RESULTS: There were no significant associations of maternal blood Hg level with birthweight, head circumference or crown-heel length in adjusted linear regression models. Similarly, there were no increased odds of low birthweight or preterm delivery in adjusted logistic regression models. When the models were repeated after stratification into fish-eaters and there were no associations except for a negative association with birthweight in non-fish eaters (unstandardised B coefficient -58.4 (95% confidence interval -113.8, -3.0) g, p=0.039). CONCLUSION: Moderate mercury levels in pregnancy were not associated with anthropometric variables, or on the odds of low birthweight or preterm birth. Fish consumption may have a protective effect on birthweight. Consumption of fish in line with government guidelines during pregnancy should be encouraged. PMID- 27252154 TI - H2O2 generated from mitochondrial electron transport chain in thoracic perivascular adipose tissue is crucial for modulation of vascular smooth muscle contraction. AB - The perivascular adipose tissue (PVAT) releases a variety of factors that affect vascular function. PVAT in the thoracic aorta shares characteristics with the brown adipose tissue, including a large amount of mitochondria. PVAT-derived factors influence both endothelial and smooth muscle function via several signaling mechanisms including the release/generation of reactive nitrogen and oxygen species. Considering the importance of reactive oxygen species (ROS) on vascular function and that mitochondria are an important source of ROS, we hypothesized that mitochondria-derived ROS in the PVAT modulates vascular reactivity. Vascular reactivity to norephinephrine (NE) was evaluated in thoracic aortic rings, with or without endothelium and/or PVAT, from male Wistar rats. Mitochondrial uncoupling, as well as hydrogen peroxide (H2O2) removal, increased the contraction in vessels surrounded by PVAT. PVAT stimulated with NE exhibited increased protein expression, determined by Western blot analysis, of manganese superoxide dismutase (Mn-SOD) and decreased protein expression of catalase. Ultimately, NE increased superoxide anion (O2(-)) generation in PVAT via increases in intracellular calcium. These results clearly demonstrate that mitochondrial electron transport chain (mETC) in PVAT contributes to modulation of aortic muscle contraction by generating higher amounts of O2(-) that is, in turn, dismutated to hydrogen peroxide, which then acts as a pivotal signaling molecule regulating vascular smooth muscle contraction. PMID- 27252155 TI - Gain or non-loss: The message matching effect of regulatory focus on moral judgements of other-orientation lies. AB - Previous studies found that individuals with promotion focus are more likely to be persuaded by messages framed in terms of gain-related words; individuals with prevention focus are more likely to be persuaded by messages framed in terms of loss-related words. This is known as the message matching effect of regulatory focus. The present study extended this effect into the field of moral judgement of other-orientation lies. Two experiments were conducted, revealing that (a) individuals with promotion focus judged gain-framed other-orientation lies to be more moral, while individuals with prevention focus judged non-loss-framed other orientation lies to be more moral; and (b) the subjective processing fluency had a partial mediating role in the message matching effect. Theoretical implications and future research directions were discussed. PMID- 27252156 TI - D-serine transporter in Staphylococcus saprophyticus identified. AB - Among staphylococci Staphylococcus saprophyticus is the only species that is typically uropathogenic and an important cause of urinary tract infections in young women. The amino acid D-serine occurs in relatively high concentrations in human urine and has a bacteriostatic or toxic effect on many bacteria. In uropathogenic Escherichia coli and S. saprophyticus, the amino acid regulates the expression of virulence factors and can be used as a nutrient. The ability of uropathogens to respond to or to metabolize D-serine has been suggested as a factor that enables colonization of the urinary tract. Until now nothing is known about D-serine transport in S. saprophyticus We generated mutants of putative transporter genes in S. saprophyticus 7108 that show homology to the D-serine transporter cycA of E. coli and tested them in a D-serine depletion assay to analyze the D-serine uptake rate of the cells. The mutant of SPP1070 showed a strong decrease in D-serine uptake. Therefore, SSP1070 was identified as a major D-serine transporter in S. saprophyticus 7108 and was named D-serine transporter A (DstA). D-serine caused a prolonged lag phase of S. saprophyticus in a chemically defined medium. This negative effect was dependent on the presence of DstA. PMID- 27252157 TI - Molecular dissection of blaKPC-2-bearing plasmids evolving in Klebsiella pneumoniae isolated at one teaching hospital in Shanghai, China. AB - The presence of carbapenemase gene blaKPC-2 in a wide variety of plasmids, especially conjugative plasmids, is key to the rapid, worldwide spread of carbapenemase enzymes. Thirty-eight, non-duplicated, carbapenem-resistant, clinical Klebsiella pneumoniae isolates were collected, all carrying blaKPC-2 bearing plasmids. Relaxase analysis was used to classify these plasmids; 8 and 30 plasmids belonged to the MOBP3 and MOBF12 subfamilies, respectively. Phylogenetic analysis revealed two genetic subclades in the MOBF12 subfamily and suggested that these subclades might not have originated from the same ancestor. Crossing PCR, used to sequence fully the type IV secretion system (T4SS, essential structures for conjugative plasmids) of the MOBF12 plasmids, found that T4SSs were distinctively different in certain functional genes, e.g. traS and traG. In conclusion, this study delineated the evolution of blaKPC-2-bearing plasmids at Huashan Hospital, Shanghai, China. The plasmids bearing blaKPC-2 were diverse and the MOBF12 plasmids were dominant in clinical K. pneumoniae isolates. PMID- 27252158 TI - Homeostasis - the Walter B. Cannon's Legacy - Applied to the Metabolic Syndrome and the Scientific Enterprise. PMID- 27252159 TI - Physiology in Perspective: Physiological Transitions During Our Lifespan. PMID- 27252161 TI - Aromatase: Contributions to Physiology and Disease in Women and Men. AB - Aromatase (estrogen synthetase; EC 1.14.14.1) catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. Aromatase is most widely known for its roles in reproduction and reproductive system diseases, and as a target for inhibitor therapy in estrogen-sensitive diseases including cancer, endometriosis, and leiomyoma (141, 143). However, all tissues contain estrogen receptor-expressing cells, the majority of genes have a complete or partial estrogen response element that regulates their expression (61), and there are plentiful nonreceptor effects of estrogens (79); therefore, the effect of aromatase through the provision of estrogen is almost universal in terms of health and disease. This review will provide a brief but comprehensive overview of the enzyme, its role in steroidogenesis, the problems that arise with its functional mutations and mishaps, the roles in human physiology of aromatase and its product estrogens, its current clinical roles, and the effects of aromatase inhibitors. While much of the story is that of the consequences of the formation of its product estrogens, we also will address alternative enzymatic roles of aromatase as a demethylase or nonenzymatic actions of this versatile molecule. Although this short review is meant to be thorough, it is by no means exhaustive; rather, it is meant to reflect the cutting-edge, exciting properties and possibilities of this ancient enzyme and its products. PMID- 27252160 TI - The VCD Mouse Model of Menopause and Perimenopause for the Study of Sex Differences in Cardiovascular Disease and the Metabolic Syndrome. AB - In females, menopause, the cessation of menstrual cycling, is associated with an increase in risk for several diseases such as cardiovascular disease, osteoporosis, diabetes, the metabolic syndrome, and ovarian cancer. The majority of women enter menopause via a gradual reduction of ovarian function over several years (perimenopause) and retain residual ovarian tissue. The VCD mouse model of menopause (ovarian failure in rodents) is a follicle-deplete, ovary-intact animal that more closely approximates the natural human progression through perimenopause and into the postmenopausal stage of life. In this review, we present the physiological parameters of how to use the VCD model and explore the VCD model and its application into the study of postmenopausal disease mechanisms, focusing on recent murine studies of diabetic kidney disease, the metabolic syndrome, and hypertension. PMID- 27252162 TI - Transcriptional Dysregulation of Adipose Tissue Autophagy in Obesity. AB - There is growing interest in understanding how dysregulated autophagy may contribute to pathogenesis of disease. Most frequently, disease states are associated with diminished autophagy, mostly attributed to genetic variation in autophagy genes and/or to dysfunctional posttranscriptional mechanisms. In human adipose tissue (AT), in obesity, expression of autophagy genes is upregulated and autophagy is likely activated, associating with adipose dysfunction. This review explores the emerging role of transcriptional mechanisms regulating AT autophagy in obesity. PMID- 27252163 TI - Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance. AB - Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ~100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. PMID- 27252165 TI - Residual Force Enhancement Following Eccentric Contractions: A New Mechanism Involving Titin. AB - Eccentric muscle properties are not well characterized by the current paradigm of the molecular mechanism of contraction: the cross-bridge theory. Findings of force contributions by passive structural elements a decade ago paved the way for a new theory. Here, we present experimental evidence and theoretical support for the idea that the structural protein titin contributes to active force production, thereby explaining many of the unresolved properties of eccentric muscle contraction. PMID- 27252164 TI - Viewing Extrinsic Proteotoxic Stress Through the Lens of Amyloid Cardiomyopathy. AB - Proteotoxicity refers to toxic stress caused by misfolded proteins of extrinsic or intrinsic origin and plays an integral role in the pathogenesis of cardiovascular diseases. Herein, we provide an overview of the current understanding of mechanisms underlying proteotoxicity and its contribution in the pathogenesis of amyloid cardiomyopathy. PMID- 27252166 TI - Why is UEFA carrying out injury studies? PMID- 27252167 TI - UEFA making vital contribution to football medicine. PMID- 27252168 TI - Can off-field 'brains' provide a competitive advantage in professional football? PMID- 27252169 TI - Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naive B cells. AB - Neonatal innate immunity is distinct from that of adults, which may contribute to increased susceptibility to infection and limit vaccine responses. B cells play critical roles in protection from infection and detect PAMPs via TLRs, that, when co-activated with CD40, can drive B-cell proliferation and Ab production. We characterized the expression of TLRs in circulating B cells from newborns and adults, and evaluated TLR- and CD40-mediated naive B-cell class-switch recombination (CSR) and cytokine production. Gene expression levels of most TLRs was similar between newborn and adult B cells, except that newborn naive B cells expressed more TLR9 than adult naive B cells. Neonatal naive B cells demonstrated impaired TLR2- and TLR7- but enhanced TLR9-mediated cytokine production. Significantly fewer newborn naive B cells underwent CSR to produce IgG, an impairment also noted with IL-21 stimulation. Additionally, co-stimulation via CD40 and TLRs induced greater cytokine production in adult B cells. Thus, while newborn naive B cells demonstrate adult-level expression of TLRs and CD40, the responses to stimulation of these receptors are distinct. Relatively high expression of TLR9 and impaired CD40-mediated Ig secretion contributes to distinct innate and adaptive immunity of human newborns and may inform novel approaches to early-life immunization. PMID- 27252170 TI - Myeloid cell-specific inositol polyphosphate-4-phosphatase type I knockout mice impair bacteria clearance in a murine peritonitis model. AB - Phosphatidylinositol 3-kinase (PI3K)/Akt signaling has been implicated in the anti-inflammatory response in a mouse model of endotoxemia and sepsis. The present study focused on the role of inositol polyphosphate-4-phosphatase type I (Inpp4a), which dephosphorylates PtdIns(3,4)P2 to PtdIns(3)P, in bacterial infections. We prepared myeloid cell-specific Inpp4a-conditional knockout mice. Macrophages from these mice showed increased Akt phosphorylation and reduced production of inflammatory cytokines in response to LPS or Escherichia coli in vitro The Inpp4a knockout mice survived for a shorter time than wild type mice after i.p. infection with E. coli, with less production of inflammatory cytokines. Additionally, E. coli clearance from blood and lung was significantly impaired in the knockout mice. A likely mechanism is that the Inpp4a-catalyzed dephosphorylation of PtdIns(3,4)P2 down-regulates Akt pathways, which, in turn, increases the production of inflammatory mediators. This mechanism at least fits the decreased E. coli clearance and short survival in the Inpp4a knockout mice. PMID- 27252172 TI - Erratum for the Research Article: "Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency" by S. S. De Ravin, X. Wu, S. Moir, S. Anaya-O'Brien, N. Kwatemaa, P. Littel, N. Theobald, U. Choi, L. Su, M. Marquesen, D. Hilligoss, J. Lee, C. M. Buckner, K. A. Zarember, G. O'Connor, D. McVicar, D. Kuhns, R. E. Throm, S. Zhou, L. D. Notarangelo, I. C. Hanson, M. J. Cowan, E. Kang, C. Hadigan, M. Meagher, J. T. Gray, B. P. Sorrentino, H. L. Malech. PMID- 27252171 TI - Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo. AB - The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested. Upon stimulation of murine macrophages, G-CSF secretion and NO production were strongly augmented by all TDXs tested, in a wide concentration range. In contrast, the TMXs triggered macrophage activation only at high concentrations. Macrophage activation by all TDXs required Mincle, but was independent of MyD88. The superior capacity of TDXs for activating macrophages was paralleled by direct binding of TDXs, but not of TMXs, to a Mincle-Fc fusion protein. Insertion of a short polyethylene glycol between the sugar and acyl chain in TDS reduced Mincle-binding and macrophage activation. Immunization of mice with cationic liposomes containing the analogues demonstrated the superior adjuvant activity of trehalose diesters. Overall, immune activation in vitro and in vivo by trehalose esters of simple fatty acids requires two acyl chains of length and involves Mincle. PMID- 27252173 TI - What does research reproducibility mean? AB - The language and conceptual framework of "research reproducibility" are nonstandard and unsettled across the sciences. In this Perspective, we review an array of explicit and implicit definitions of reproducibility and related terminology, and discuss how to avoid potential misunderstandings when these terms are used as a surrogate for "truth." PMID- 27252174 TI - Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. AB - Toca 511 (vocimagene amiretrorepvec) is an investigational nonlytic, retroviral replicating vector (RRV) that delivers a yeast cytosine deaminase, which converts subsequently administered courses of the investigational prodrug Toca FC (extended-release 5-fluorocytosine) into the antimetabolite 5-fluorouracil. Forty five subjects with recurrent or progressive high-grade glioma were treated. The end points of this phase 1, open-label, ascending dose, multicenter trial included safety, efficacy, and molecular profiling; survival was compared to a matching subgroup from an external control. Overall survival for recurrent high grade glioma was 13.6 months (95% confidence interval, 10.8 to 20.0) and was statistically improved relative to an external control (hazard ratio, 0.45; P = 0.003). Tumor samples from subjects surviving more than 52 weeks after Toca 511 delivery disproportionately displayed a survival-related mRNA expression signature, identifying a potential molecular signature that may correlate with treatment-related survival rather than being prognostic. Toca 511 and Toca FC show excellent tolerability, with RRV persisting in the tumor and RRV control systemically. The favorable assessment of Toca 511 and Toca FC supports confirmation in a randomized phase 2/3 trial (NCT02414165). PMID- 27252176 TI - Direct measurement of T cell receptor affinity and sequence from naive antiviral T cells. AB - T cells recognize and kill a myriad of pathogen-infected or cancer cells using a diverse set of T cell receptors (TCRs). The affinity of TCR to cognate antigen is of high interest in adoptive T cell transfer immunotherapy and antigen-specific T cell repertoire immune profiling because it is widely known to correlate with downstream T cell responses. We introduce the in situ TCR affinity and sequence test (iTAST) for simultaneous measurement of TCR affinity and sequence from single primary CD8(+) T cells in human blood. We demonstrate that the repertoire of primary antigen-specific T cells from pathogen-inexperienced individuals has a surprisingly broad affinity range of 1000-fold composed of diverse TCR sequences. Within this range, samples from older individuals contained a reduced frequency of high-affinity T cells compared to young individuals, demonstrating an age related effect of T cell attrition that could cause holes in the repertoire. iTAST should enable the rapid selection of high-affinity TCRs ex vivo for adoptive immunotherapy and measurement of T cell response for immune monitoring applications. PMID- 27252178 TI - Cytomegalovirus and Epstein-Barr Virus Infections. PMID- 27252179 TI - Acquired and Congenital Hemolytic Anemia. PMID- 27252180 TI - Preventing Infections in Children with Cancer. PMID- 27252181 TI - Case 1: A 7-Year-Old with 1 Month of Ear Pain and 1 Day of Facial Weakness. PMID- 27252177 TI - Microbiota and pathogen 'pas de deux': setting up and breaking down barriers to intestinal infection. AB - The gut microbiota plays essential roles in human health and disease. In this review, we focus on the role of the intestinal microbiota in promoting resistance to infection by bacterial pathogens as well as how pathogens overcome this barrier. We discuss how the resident microbiota restricts growth and colonization of invading pathogens by limiting availability of nutrients and through generation of a hostile environment. Additionally, we examine how microbiota derived signaling molecules interfere with bacterial virulence. In turn, we discuss how pathogens exploit non-competitive metabolites to replicate in vivo as well as to precisely control virulence and cause disease. This bacterial two step of creating and overcoming challenges important in preventing and establishing infection highlights the complexities of elucidating interactions between the commensal bacteria and pathogens. Better understanding of microbiota-pathogen interplay will have significant implications for developing novel therapeutics to treat infectious diseases. PMID- 27252182 TI - Case 2: Fever and Seizures in a 10-month-old Girl from Nigeria. PMID- 27252184 TI - Correction. PMID- 27252183 TI - Case 3: Recurrent Vomiting and 60-lb Weight Loss in a 17-year-old Girl. PMID- 27252185 TI - In Brief: Antifungal Drugs. PMID- 27252175 TI - A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. AB - Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process. PMID- 27252186 TI - Visual Diagnosis: Cough and Lip Slough: The Search for a Unifying Diagnosis. PMID- 27252188 TI - Hormones as Mediators of Phenotypic and Genetic Integration: an Evolutionary Genetics Approach. AB - Evolutionary endocrinology represents a synthesis between comparative endocrinology and evolutionary genetics. This synthesis can be viewed through the breeder's equation, a cornerstone of quantitative genetics that, in its univariate form, states that a population's evolutionary response is the product of the heritability of a trait and selection on that trait (R = h(2)S). Under this framework, evolutionary endocrinologists have begun to quantify the heritability of, and the strength of selection on, a variety of hormonal phenotypes. With specific reference to our work on testosterone and corticosterone in birds and lizards, we review these studies while emphasizing the challenges of applying this framework to hormonal phenotypes that are inherently plastic and mediate adaptive responses to environmental variation. Next, we consider the untapped potential of evolutionary endocrinology as a framework for exploring multivariate versions of the breeder's equation, with emphasis on the role of hormones in structuring phenotypic and genetic correlations. As an extension of the familiar concepts of phenotypic integration and hormonal pleiotropy, we illustrate how the hormonal milieu of an individual acts as a local environment for the expression of genes and phenotypes, thereby influencing the quantitative genetic architecture of multivariate phenotypes. We emphasize that hormones are more than mechanistic links in the translation of genotype to phenotype: by virtue of their pleiotropic effects on gene expression, hormones structure the underlying genetic variances and covariances that determine a population's evolutionary response to selection. PMID- 27252187 TI - The Emerging Role of FOXL2 in Regulating the Transcriptional Activation Function of Estrogen Receptor beta: An Insight Into Ovarian Folliculogenesis. AB - Germline mutations of the fork-head transcriptional factor forkhead box L2 (FOXL2) predispose embryos to autosomal-dominant blepharophimosis-ptosis epicanthus inversus syndrome with primary ovarian insufficiency in female patients, but the mechanisms of FOXL2 in ovarian follicular development remain elusive. Estrogens produced by ovarian granulosa cells and estrogen receptor (ER) alpha and ERbeta play fundamental roles in ovarian pathophysiology, and a previous study revealed that ERalpha and ERbeta physically interact with FOXL2. However, the underlying functions of these interactions have not been investigated. Herein, we report an ERbeta-specific repressive function of FOXL2. Histological examination demonstrated that FOXL2 expression tends to be intense during early follicular development. Immunoprecipitation revealed that ERbeta and FOXL2 interact in a ligand-independent manner. In vitro pull-down assays revealed a direct interaction between FOXL2 and the activation function (AF)-1/2 domain of ERbeta. The expression of FOXL2 represses the ligand-dependent transcriptional activation of ERbeta, but FOXL2 does not influence the ligand-dependent transcriptional activation of ERalpha. Consistent with these results, RNA interference-mediated depletion of FOXL2 stimulates the expression of the ERbeta downstream gene p450 aromatase. The convergence between FOXL2 functions and ERbeta-mediated transcription in the ovary suggests the putative mechanism of FOXL2 in early-phase follicular development, which may be partially attributed to the regulation of ERbeta-dependent gene expression. PMID- 27252189 TI - Gonads and the evolution of hormonal phenotypes. AB - Hormones are dynamic signaling molecules that influence gene activity and phenotype, and they are thus thought to play a central role in phenotypic evolution. In vertebrates, many fitness-related traits are mediated by the hormone testosterone (T), but the mechanisms by which T levels evolve are unclear. Here, we summarize a series of studies that advance our understanding of these mechanisms by comparing males from two subspecies of dark-eyed junco (Junco hyemalis) that differ in aggression, body size, and ornamentation. We first review our research demonstrating population differences in the time-course of T production, as well as findings that point to the gonad as a major source of this variation. In a common garden, the subspecies do not differ in pituitary output of luteinizing hormone, but males from the more androgenized subspecies have greater gonadal gene expression for specific steroidogenic enzymes, and they may be less sensitive to feedback along the hypothalamo-pituitary-gonadal (HPG) axis. Furthermore, we present new data from a common garden study demonstrating that the populations do not differ in gonadal sensitivity to gonadotropin-inhibitory hormone (i.e., GnIH receptor mRNA abundance), but the more androgenized subspecies expresses less gonadal mRNA for glucocorticoid receptor and mineralocorticoid receptor, suggesting altered cross-talk between the hypothalamo pituitary-gonadal and -adrenal axes as another mechanism by which these subspecies have diverged in T production. These findings highlight the diversity of mechanisms that may generate functional variation in T and influence hormone mediated phenotypic evolution. PMID- 27252191 TI - Transcriptional Profiling of Metabolic Transitions during Development and Diapause Preparation in the Copepod Calanus finmarchicus. AB - Calanus finmarchicus, like many other copepods in the family Calanidae, can enter into a facultative diapause during the last juvenile phase (fifth copepodid, C5) to enable survival during unfavorable periods. Diapause is essential to the persistence of Calanus populations and profoundly impacts energy flow within oceanic ecosystems, yet regulation of diapause is not understood in these animals. Transcriptional profiling has begun to provide insight into metabolic changes occurring as C. finmarchicus prepares for and enters into diapause or skips diapause to prepare for the terminal molt. In particular, components of the glycolysis, pentose phosphate and lipid synthesis pathways are upregulated early in the C5 stage when lipid stores are low. Currently, our ability to identify metabolic patterns is limited by the incomplete functional annotation of the C. finmarchicus transcriptome. Such limitations are widespread among studies of non model organisms and addressing them should be a priority for future research. In addition, integrating the results across multiple emerging complementary transcriptomic studies will provide a more complete picture of copepod physiology than isolated studies. Ultimately, identifying molecular markers of copepod physiology could enable robust identification of animals preparing to enter into diapause and ultimately lead to a greatly improved understanding of diapause regulation. PMID- 27252190 TI - Relationships between Endocrine Traits and Life Histories in Wild Animals: Insights, Problems, and Potential Pitfalls. AB - The endocrine mechanisms causing variation and plasticity in life history traits (e.g., development time, mass at birth/hatching, rate of postnatal growth, age or size at sexual maturity, litter or clutch size, annual survival, and lifespan) or fitness (annual or lifetime reproductive success) have recently garnered considerable interest. We review three issues facing studies that quantify relationships between endocrine traits and life histories or measures of fitness and describe possible solutions using insights from evolutionary ecology. We focus in particular on the steroid hormones glucocorticoids that are involved in the vertebrate neuroendocrine stress response. First, context-dependent associations between endocrine traits and life histories or fitness are widespread, and therefore, it is important to quantify how intrinsic or extrinsic factors modify these relationships. Second, studies in evolutionary endocrinology may aspire to quantify patterns of natural selection on endocrine traits, but this may not tell us how they influence fitness. Studies that also identify the actual targets of selection that the endocrine traits are influencing will be very useful. Third, environmental or intrinsic factors can cause co-variance between endocrine traits and life histories or fitness. This is problematic for interpreting the potential evolutionary consequences of selection on endocrine traits, but it can also produce divergent answers for relationships between endocrine traits and life histories or fitness depending upon whether the data are analyzed in an among- or within-year framework. Future long-term studies following uniquely marked individuals over their lifetime (longitudinal individual-based approach) in combination with experimental manipulations of the endocrine traits or environmental factors influencing both endocrine traits and life histories or fitness may help to produce new insights in evolutionary endocrinology despite these issues. This is an ambitious endeavor, and we briefly review some of the key issues facing such long-term studies and experimental manipulations of endocrine traits. PMID- 27252192 TI - New Lessons from an Old Fish: What Antarctic Icefishes May Reveal about the Functions of Oxygen-Binding Proteins. AB - The loss of expression of the oxygen-binding protein hemoglobin (Hb) in the family Channichthyidae (suborder Notothenioidei) of Antarctic fishes is considered a disaptation that has persisted because of the unusual conditions prevailing in the Southern Ocean during the evolution of the family. The loss of expression of the intracellular oxygen-binding protein myoglobin (Mb) in heart ventricles is more of a conundrum because it occurred at four points during the radiation of the family, suggesting weakened selective pressure maintaining expression of the protein. Yet, studies have shown that when present, Mb enhances function. Here, I discuss potential reasons for weakened selective pressure maintaining Mb expression in light of the multiple functions proposed for Mb. Additionally, I discuss results from recent studies exploring the possibility that the loss of Hb and Mb may be advantageous because it reduces the production of reactive oxygen species, levels of oxidized proteins, and the energetic costs associated with replacing oxidatively damaged proteins. PMID- 27252194 TI - Biological Impacts of Thermal Extremes: Mechanisms and Costs of Functional Responses Matter. AB - Thermal performance curves enable physiological constraints to be incorporated in predictions of biological responses to shifts in mean temperature. But do thermal performance curves adequately capture the biological impacts of thermal extremes? Organisms incur physiological damage during exposure to extremes, and also mount active compensatory responses leading to acclimatization, both of which alter thermal performance curves and determine the impact that current and future extremes have on organismal performance and fitness. Thus, these sub-lethal responses to extreme temperatures potentially shape evolution of thermal performance curves. We applied a quantitative genetic model and found that beneficial acclimatization and cumulative damage alter the extent to which thermal performance curves evolve in response to thermal extremes. The impacts of extremes on the evolution of thermal performance curves are reduced if extremes cause substantial mortality or otherwise reduce fitness differences among individuals. Further empirical research will be required to understand how responses to extremes aggregate through time and vary across life stages and processes. Such research will enable incorporating passive and active responses to sub-lethal stress when predicting the impacts of thermal extremes. PMID- 27252195 TI - Migration, Prospecting, Dispersal? What Host Movement Matters for Infectious Agent Circulation? AB - Spatial disease ecology is emerging as a new field that requires the integration of complementary approaches to address how the distribution and movements of hosts and parasites may condition the dynamics of their interactions. In this context, migration, the seasonal movement of animals to different zones of their distribution, is assumed to play a key role in the broad scale circulation of parasites and pathogens. Nevertheless, migration is not the only type of host movement that can influence the spatial ecology, evolution, and epidemiology of infectious diseases. Dispersal, the movement of individuals between the location where they were born or bred to a location where they breed, has attracted attention as another important type of movement for the spatial dynamics of infectious diseases. Host dispersal has notably been identified as a key factor for the evolution of host-parasite interactions as it implies gene flow among local host populations and thus can alter patterns of coevolution with infectious agents across spatial scales. However, not all movements between host populations lead to dispersal per se. One type of host movement that has been neglected, but that may also play a role in parasite spread is prospecting, i.e., movements targeted at selecting and securing new habitat for future breeding. Prospecting movements, which have been studied in detail in certain social species, could result in the dispersal of infectious agents among different host populations without necessarily involving host dispersal. In this article, we outline how these various types of host movements might influence the circulation of infectious disease agents and discuss methodological approaches that could be used to assess their importance. We specifically focus on examples from work on colonial seabirds, ticks, and tick-borne infectious agents. These are convenient biological models because they are strongly spatially structured and involve relatively simple communities of interacting species. Overall, this review emphasizes that explicit consideration of the behavioral and population ecology of hosts and parasites is required to disentangle the relative roles of different types of movement for the spread of infectious diseases. PMID- 27252193 TI - Hormones and the Evolution of Complex Traits: Insights from Artificial Selection on Behavior. AB - Although behavior may often be a fairly direct target of natural or sexual selection, it cannot evolve without changes in subordinate traits that cause or permit its expression. In principle, changes in endocrine function could be a common mechanism underlying behavioral evolution because they are well positioned to mediate integrated responses to behavioral selection. More specifically, hormones can influence both motivational (e.g., brain) and performance (e.g., muscles) components of behavior simultaneously and in a coordinated fashion. If the endocrine system is often "used" as a general mechanism to effect responses to selection, then correlated responses in other aspects of behavior, life history, and organismal performance (e.g., locomotor abilities) should commonly occur because any cell with appropriate receptors could be affected. Ways in which behavior coadapts with other aspects of the phenotype can be studied directly through artificial selection and experimental evolution. Several studies have targeted rodent behavior for selective breeding and reported changes in other aspects of behavior, life history, and lower-level effectors of these organismal traits, including endocrine function. One example involves selection for high levels of voluntary wheel running, one aspect of physical activity, in four replicate High Runner (HR) lines of mice. Circulating levels of several hormones (including insulin, testosterone, thyroxine, triiodothyronine) have been characterized, three of which-corticosterone, leptin, and adiponectin-differ between HR and control lines, depending on sex, age, and generation. Potential changes in circulating levels of other behaviorally and metabolically relevant hormones, as well as in other components of the endocrine system (e.g., receptors), have yet to be examined. Overall, results to date identify promising avenues for further studies on the endocrine basis of activity levels. PMID- 27252196 TI - Endocrine Proxies Can Simplify Endocrine Complexity to Enable Evolutionary Prediction. AB - It is well understood that much of evolutionary change is mediated through the endocrine system with growing interest to identify how this occurs. This however, causes a conflict of sorts. To understand endocrine mechanism, a focus on detail is required. In contrast, to understand evolutionary change, reduction to a few key traits is essential. Endocrine proxies, measurable traits that accurately reflect specific hormonal titers or the timing of specific hormonal events, can reduce endocrine complexity to a few traits that enable predictions of how the endocrine system regulates evolutionary change. In the tobacco hornworm (Manduca sexta, Sphingidae), three endocrine proxies, measured on 5470 individuals, were used to test explicit predictions of how the endocrine system regulates the response to 10 generations of simultaneous selection on body size and development time. The critical weight (CW) reflects the variation in the cessation of juvenile hormone (JH) secretion in the last larval instar, the interval to cessation of growth (ICG) reflects the variation in prothoracicotropic hormone and 20-hydroxyecdysone (20E). Growth rate (GR) reflects the nutrient signaling pathways, primarily the insulin and TOR This is a standard identity similar to DNA signaling pathways. These three endocrine proxies explained 99% and 93% of the variation in body size and development time, respectively, following the 10 generations of simultaneous selection. When the two focal traits, body size and development time, were selected in the same direction, both to either increase or both to decrease, the response to selection was determined primarily by the CW and the ICG, proxies for the developmental hormones JH and 20E, and constrained by GR. In contrast, when the two focal traits were selected in opposite directions, one to increase and the other to decrease, the response to selection was determined primarily by the insulin and TOR signaling pathways as measured by their proxy, GR, and constrained by the CW and the ICG. Thus, the use of endocrine proxies may be a powerful tool to reduce endocrine complexity to enable explicit and testable predictions how the endocrine system can enable or constrain evolutionary change. PMID- 27252197 TI - Introduction to the Symposium: Beyond the Mean: Biological Impacts of Changing Patterns of Temperature Variation. PMID- 27252198 TI - Studying Genital Coevolution to Understand Intromittent Organ Morphology. AB - Male intromittent organs are exceedingly diverse, yet we know comparatively little about female genital diversity. However, the most direct mechanical interaction between males and females occurs during copulation, and therefore, genital coevolution is expected to be widespread. This means that diversification of male structures must influence diversity of female genital features and vice versa. As we expand our understanding of coevolutionary interactions between the sexes, we need to expand our knowledge of three basic areas: First, we need quantitative data, on morphological variation of female genitalia. Second, we need to study the mechanics of copulatory interactions, and third, we need to use this understanding to determine which features of genital morphology are under selection, and how their variable morphology and function may affect fitness. Though studying coevolution is certainly difficult, this knowledge is crucial to our understanding of diversity in morphology of the male intromittent organ. PMID- 27252199 TI - Morphological characteristics regulating phallic glans engorgement in the American alligator. AB - The distal part of the crocodilian phallus consists of a bulbous glans containing well-developed vascular tissues that can inflate before or during sexual activity, enlarging and elaborating the glans into a complex, though still functionally undefined, copulatory structure. An enlarged glans putatively interacts with the female cloaca and may change the shape of her reproductive tract to facilitate insemination and increase the probability of fertilization. Here, we investigated the cellular-level properties of the glans and other inflatable phallic tissues associated with the sperm-conducting sulcus spermaticus in the American alligator (Alligator mississippiensis). Using histochemical staining, we visualized and defined collagen and elastin fiber densities and orientations in these tissues. Extracellular matrix architectures provided insights about phallic glans material properties and how they may affect tissue strength and flexibility during inflation and in response to copulatory forces. We also investigated the potential sources of fluids that induce inflation in alligator phalli. Combining serial sectioning and three-dimensional reconstruction, we identified a pair of supracrucal plexus vascular bodies at the proximal end of the alligator phallus that extend distally adjacent to ventro medial sulcus tissues. Together, our gross and histological examination of the American alligator phallic glans suggests that its tissues are arranged in a manner that would allow vascular inflation to expand the glans to a specific and repeatable shape, and potentially release secretory products into the female reproductive tract. Both elements could play roles in postcopulatory sexual selection, by mechanically and/or chemically affecting female reproductive physiology. PMID- 27252200 TI - Diverse Distributions of Extraocular Opsins in Crustaceans, Cephalopods, and Fish. AB - Non-visual and extraocular photoreceptors are common among animals, but current understanding linking molecular pathways to physiological function of these receptors is lacking. Opsin diversity in extraocular tissues suggests that many putative extraocular photoreceptors utilize the "visual" phototransduction pathway-the same phototransduction pathway as photoreceptors within the retina dedicated to light detection for image sensing. Here, we provide a brief overview of the current understanding of non-visual and extraocular photoreceptors, and contribute a synopsis of several novel putative extraocular photoreceptors that use both visual and non-visual phototransduction pathways. Crayfish, cephalopods, and flat fish express opsins in diverse tissues, suggesting the presence of extraocular photoreceptors. In most cases, we find that these animals use the same phototransduction pathway that is utilized in the retinas for image formation. However, we also find the presence of non-visual phototransduction components in the skin of flounders. Our evidence suggests that extraocular photoreceptors may employ a number of phototransduction pathways that do not appear to correlate with purpose or location of the photoreceptor. PMID- 27252201 TI - Life in the Frequency Domain: the Biological Impacts of Changes in Climate Variability at Multiple Time Scales. AB - Over the last few decades, biologists have made substantial progress in understanding relationships between changing climates and organism performance. Much of this work has focused on temperature because it is the best kept of climatic records, in many locations it is predicted to keep rising into the future, and it has profound effects on the physiology, performance, and ecology of organisms, especially ectothermic organisms which make up the vast majority of life on Earth. Nevertheless, much of the existing literature on temperature organism interactions relies on mean temperatures. In reality, most organisms do not directly experience mean temperatures; rather, they experience variation in temperature over many time scales, from seconds to years. We propose to shift the focus more directly on patterns of temperature variation, rather than on means per se, and present a framework both for analyzing temporal patterns of temperature variation and for incorporating those patterns into predictions about organismal biology. In particular, we advocate using the Fourier transform to decompose temperature time series into their component sinusoids, thus allowing transformations between the time and frequency domains. This approach provides (1) standardized ways of visualizing the contributions that different frequencies make to total temporal variation; (2) the ability to assess how patterns of temperature variation have changed over the past half century and may change into the future; and (3) clear approaches to manipulating temporal time series to ask "what if" questions about the potential effects of future climates. We first summarize global patterns of change in temperature variation over the past 40 years; we find meaningful changes in variation at the half day to yearly times scales. We then demonstrate the utility of the Fourier framework by exploring how power added to different frequencies alters the overall incidence of long-term waves of high and low temperatures, and find that power added to the lowest frequencies greatly increases the probability of long-term heat and cold waves. Finally, we review what is known about the time scales over which organismal thermal performance curves change in response to variation in the thermal environment. We conclude that integrating information characterizing both the frequency spectra of temperature time series and the time scales of resulting physiological change offers a powerful new avenue for relating climate, and climate change, to the future performance of ectothermic organisms. PMID- 27252202 TI - Ecological Immunology through the Lens of Exercise Immunology: New Perspective on the Links between Physical Activity and Immune Function and Disease Susceptibility in Wild Animals. AB - Locomotion and other physical activities by free-living animals may influence immune function and disease susceptibility. This influence may be a consequence of energetic trade-offs or other mechanisms that are often, but not always, inseparably linked to an animal's life history (e.g., flight and migration). Ecological immunology has mainly focused on these life-history trade-offs, overlooking the possible effects of physical activity per se on immune function and disease susceptibility. In this review, we explore the field of exercise immunology, which examines the impact of exercise on immune function and disease susceptibility in humans, with the aim of presenting new perspectives that might be transferable to ecological immunology. First, we explore key concepts in exercise immunology that could be extended to animals. Next, we investigate the concept "exercise" in animals, and propose the use of "physical activity" instead. We briefly discuss methods used in animals to quantify physical activity in terms of energy expenditure and summarize several examples of animals engaging in physical activity. Then, we highlight potential consequences of physical activity on immune function and disease susceptibility in animals, together with an overview of animal studies that examine these links. Finally, we explore and discuss the potential for incorporating perspectives from exercise immunology into ecological immunology. Such integration could help advance our understanding of human and animal health and contribute new ideas to budding "One Health" initiatives. PMID- 27252203 TI - The Landscape of Evolution: Reconciling Structural and Dynamic Properties of Metabolic Networks in Adaptive Diversifications. AB - The network of the interactions among genes, proteins, and metabolites delineates a range of potential phenotypic diversifications in a lineage, and realized phenotypic changes are the result of differences in the dynamics of the expression of the elements and interactions in this deterministic network. Regulatory mechanisms, such as hormones, mediate the relationship between the structural and dynamic properties of networks by determining how and when the elements are expressed and form a functional unit or state. Changes in regulatory mechanisms lead to variable expression of functional states of a network within and among generations. Functional properties of network elements, and the magnitude and direction of evolutionary change they determine, depend on their location within a network. Here, we examine the relationship between network structure and the dynamic mechanisms that regulate flux through a metabolic network. We review the mechanisms that control metabolic flux in enzymatic reactions and examine structural properties of the network locations that are targets of flux control. We aim to establish a predictive framework to test the contributions of structural and dynamic properties of deterministic networks to evolutionary diversifications. PMID- 27252204 TI - Ontogenetic Allometry in Shape and Flexibility Underlies Life History Patterns of Labrid Cleaning Behavior. AB - Body shape plays a crucial role in the movement of organisms. In the aquatic environment, the shape of the body, fins, and the underlying axial skeleton reflect the ability of organisms to propel and maneuver through water. Ontogenetic changes in body shape and flexibility of the axial skeleton may coincide with shifts in ecology (e.g., changes in habitat or feeding mode). We use the evolution of cleaning behavior in the Labridae (wrasses and parrotfishes) as a case study. Cleaner fishes are species that remove and consume ectoparasites from other organisms. In many cases, cleaning involves a high degree of maneuverability, as cleaners on the hunt for parasites may continuously dart around the body of their clients. In labrids, at least 58 species are known to clean. Over two-thirds of these species, however, clean predominately as juveniles, exhibiting an ontogenetic shift away from cleaning as they enter adulthood. Using a phylogenetic comparative framework, we examined features of the axial skeleton, overall body shape, and pectoral fin shape in 31 species of labrids spread across four major clades to assess how scaling patterns in these systems are associated with the ontogeny of cleaning behavior. We find that across wrasses, the ontogeny of body shape shows evolutionary concordance with the degree of flexibility across the vertebral column. A key driver of this relationship is that species that shift away from cleaning over ontogeny show stronger positive allometry for body depth and vertebral moment of inertia than other taxa. Species that clean throughout their life histories show a more elongate body and vertebral column, and tend to maintain the combination of these characteristics over ontogeny. Cleaning behavior in labrid fishes is thus an excellent model with which to investigate morphological patterns as they relate to evolution, development, and ecology. PMID- 27252205 TI - Transcriptional Profiling of Banana Shrimp Fenneropenaeus merguiensis with Differing Levels of Viral Load. AB - Viral pathogens are of serious concern to the culture of penaeid shrimps worldwide. However, little is known about the molecular response of shrimp to viral infection. Selective breeding has been suggested as an effective long-term strategy to manage viral disease, though more information on gene function is needed to help inform breeding programs. The study of cultured banana shrimp (Fenneropenaeus merguiensis) infected with hepatopancreatic parvo-like virus (HPV) provides a unique opportunity to explore the host response to viral infection independent of challenge testing. To gain insight into the genetic mechanisms underlying resistance to high levels of HPV, we examined hepatopancreas tissue from six full-sib groups of banana shrimp with differing levels of HPV infection for differences in gene expression. A total of 404 differentially expressed genes were identified with 180 being over-expressed and 224 under-expressed among high-HPV full-sib groups. Based on homology analysis, a large proportion of these genes were associated with processes reported to be involved in the immune response of crustaceans, including pattern recognition proteins, antimicrobial peptides, components of the prophenoloxidase system, and antiviral activity. The results indicate shrimp from high-HPV full-sib groups appear to have a lower presence of important immune response elements, yet possess upregulated putative antiviral pathways. Within the differentially expressed genes, over 4000 sequence variants were identified to be exclusive to either the high- or low-HPV full-sib groups. To our knowledge, this is the first report of differential expression analysis using RNA-Seq to explore differences in viral load among high- and low-HPV full-sib groups of cultured shrimp. This research has provided additional insight into our understanding of the mechanisms involved in the response of this shrimp species to a naturally occurring viral pathogen. Sequence variants identified in this study offer an exceptional resource for mining gene-associated markers of HPV resistance. PMID- 27252206 TI - The Distribution and Abundance of Parasites in Aquatic Ecosystems in a Changing Climate: More than Just Temperature. AB - SynopsisEvaluation of the potential response of parasites of aquatic organisms to climate change illustrates the complexity of host-parasite relationships and the difficulty of making accurate predictions for these biological systems. In recent years, trematodes have proven to be a useful model to evaluate potential effects of climate change on host-parasite systems. In the first part of this article, I review and summarize results from the recent use of trematodes and specifically their early life cycle stages in testing effects of temperature and other climate driven variables on life history traits and host-parasite interactions. However, metazoan parasites in aquatic systems respond directly to changes in temperature and also to changes in other climate-driven abiotic parameters that are mediated directly on the parasite or indirectly through changes in the distribution and abundance of their hosts. In addition, though most research to date has focused on the effects of temperature, it is imperative to explore effects of precipitation, eutrophication, acidification, water levels and flow rates, habitat loss and fragmentation, extreme weather, and other forms of anthropogenic interference on the distribution of both hosts and parasites, as these biotic and abiotic factors and stressors do not operate independently of climate. In the second part of this article, the effects of some of these factors derived from our own field studies, as well as other investigations both in the laboratory and the field, on the distribution, abundance, and community structure of parasites in aquatic ecosystems will be reviewed and discussed. PMID- 27252207 TI - Migratory monarchs wintering in California experience low infection risk compared to monarchs breeding year-round on non-native milkweed. AB - Long-distance migration can lower infection risk for animal populations by removing infected individuals during strenuous journeys, spatially separating susceptible age classes, or allowing migrants to periodically escape from contaminated habitats. Many seasonal migrations are changing due to human activities including climate change and habitat alteration. Moreover, for some migratory populations, sedentary behaviors are becoming more common as migrants abandon or shorten their journeys in response to supplemental feeding or warming temperatures. Exploring the consequences of reduced movement for host-parasite interactions is needed to predict future responses of animal pathogens to anthropogenic change. Monarch butterflies (Danaus plexippus) and their specialist protozoan parasite Ophryocystis elektroscirrha (OE) provide a model system for examining how long-distance migration affects infectious disease processes in a rapidly changing world. Annual monarch migration from eastern North America to Mexico is known to reduce protozoan infection prevalence, and more recent work suggests that monarchs that forego migration to breed year-round on non-native milkweeds in the southeastern and south central Unites States face extremely high risk of infection. Here, we examined the prevalence of OE infection from 2013 to 2016 in western North America, and compared monarchs exhibiting migratory behavior (overwintering annually along the California coast) with those that exhibit year-round breeding. Data from field collections and a joint citizen science program of Monarch Health and Monarch Alert showed that infection frequency was over nine times higher for monarchs sampled in gardens with year round milkweed as compared to migratory monarchs sampled at overwintering sites. Results here underscore the importance of animal migrations for lowering infection risk and motivate future studies of pathogen transmission in migratory species affected by environmental change. PMID- 27252208 TI - Species Distribution Modeling of Deep Pelagic Eels. AB - The ocean's midwaters (the mesopelagic and bathypelagic zones) make up the largest living space on the planet, but are undersampled and relatively poorly understood. The true distribution of many midwater species, let alone the abiotic factors most important in determining that distribution, is not well known. Because collecting specimens and data from the deep ocean is expensive and logistically difficult, it would be useful to be able to predict where species of interest are likely to occur so that sampling effort can be concentrated in appropriate areas. The distribution of two representative midwater fishes, the gulper eel Eurypharynx pelecanoides and the bobtail eel Cyema atrum (Teleostei: Saccopharyngiformes), were modeled with MaxEnt software to examine the viability of species distribution modeling (SDM) for globally distributed midwater fishes using currently available environmental data from the ocean surface and bottom. These species were chosen because they are relatively abundant, easily recognized, and unlikely to have been misidentified in database records, and are true midwater fishes, not known to undertake significant vertical diurnal migration. Models for both species show a generally worldwide distribution with some exceptions, including the Southern Ocean and Bering Sea. Variable contributions show that surface and bottom environmental variables correlate with species presence. Both species are more likely to be found in areas with low levels of silicate. SDM is a promising method for better understanding the ecology of midwater organisms. PMID- 27252209 TI - Distribution of RPTLN Genes Across Reptilia: Hypothesized Role for RPTLN in the Evolution of SVMPs. AB - We report the cloning, full-length sequencing, and broad distribution of reptile specific RPTLN genes across a number of Anapsida (Testudines), Diapsida (Serpentes, Sauria), and Archosauria (Crocodylia) taxa. The remarkable structural conservation of RPTLN genes in species that had a common ancestor more than 250 million years ago, their low transcriptional level, and the lack of evidence for RPTLN translation in any reptile organ investigated, suggest for this ancient gene family a yet elusive function as long noncoding RNAs. The high conservation in extant snake venom metalloproteinases (SVMPs) of the signal peptide sequence coded for by RPTLN genes strongly suggests that this region may have played a key role in the recruitment and restricted expression of SVMP genes in the venom gland of Caenophidian snakes, some 60-50 Mya. More recently, 23-16 Mya, the neofunctionalization of an RPTLN copy in the venom gland of snakes of the genera Macrovipera and Daboia marked the beginning of the evolutionary history of a new family of disintegrins, the alpha1beta1-collagen binding antagonists, short RTS/KTS disintegrins. This evolutionary scenario predicts that venom gland RPTLN and SVMP genes may share tissue-specific regulatory elements. Future genomic studies should support or refute this hypothesis. PMID- 27252211 TI - Diet Drives the Collective Migrations and Affects the Immunity of Mormon Crickets and Locusts: A Comparison of These Potential Superspreaders of Disease. AB - Differential transmission of disease among individuals within a population or among species in a community can result in superspreaders, relatively rare individuals responsible for a large proportion of transmission events. Migrating Mormon crickets and nymphal locusts readily engage in cannibalistic attacks and necrophagy. Typically multiple individuals consume a cadaver, which fosters the spread of disease. Cannibalistic attacks result in aligned, coordinated movement of individuals in massive bands that march daily for weeks at a time. Coordinated movement reduces contact frequency, which not only reduces cannibalism but the risk of disease transmission. When crowded, Mormon crickets and locusts elevate their constitutive immunity, which further reduces the risk of disease transmission. Bands of Mormon crickets show a variety of macronutrient dietary deficiencies that determine whether they will be more susceptible to pathogenic bacteria or fungi. In some migratory bands, Mormon crickets seek carbohydrates and have less anti-bacterial activity. A lipid transport protein that functions in both fuelling migration and anti-bacterial activity may cause a trade-off between the two activities when carbohydrates are limited. In other migratory bands, Mormon crickets prefer protein over carbohydrates, indicating protein deficiency. In these bands, the generalized immunity of Mormon crickets, measured as phenoloxidase, is compromised, and the insects are more susceptible to Beauveria bassiana fungal infection. In locusts, a high protein diet resulted in greater susceptibility to another entomopathogenic fungus, Metarhizium acridum, whereas in Mormon crickets, both phenoloxidase titers and immunity to M acridum increased with adult age. Color changes associated with death by either of these fungi diminishes cannibalism, but bands may cull infected or encounter cadavers too quickly to effectively reduce fungal transmission. As long as the insects show no signs of infection that ward off their conspecifics, then infected Mormon crickets and locusts in migratory bands could be superspreaders of disease. However, the diseases that they are most likely to harbor and amplify may depend on the dietary deficiencies exhibited by members of the band. PMID- 27252210 TI - Hampered performance of migratory swans: intra- and inter-seasonal effects of avian influenza virus. AB - The extent to which animal migrations shape parasite transmission networks is critically dependent on a migrant's ability to tolerate infection and migrate successfully. Yet, sub-lethal effects of parasites can be intensified through periods of increased physiological stress. Long-distance migrants may, therefore, be especially susceptible to negative effects of parasitic infection. Although a handful of studies have investigated the short-term, transmission-relevant behaviors of wild birds infected with low-pathogenic avian influenza viruses (LPAIV), the ecological consequences of LPAIV for the hosts themselves remain largely unknown. Here, we assessed the potential effects of naturally-acquired LPAIV infections in Bewick's swans, a long-distance migratory species that experiences relatively low incidence of LPAIV infection during early winter. We monitored both foraging and movement behavior in the winter of infection, as well as subsequent breeding behavior and inter-annual resighting probability over 3 years. Incorporating data on infection history we hypothesized that any effects would be most apparent in naive individuals experiencing their first LPAIV infection. Indeed, significant effects of infection were only seen in birds that were infected but lacked antibodies indicative of prior infection. Swans that were infected but had survived a previous infection were indistinguishable from uninfected birds in each of the ecological performance metrics. Despite showing reduced foraging rates, individuals in the naive-infected category had similar accumulated body stores to re-infected and uninfected individuals prior to departure on spring migration, possibly as a result of having higher scaled mass at the time of infection. And yet individuals in the naive-infected category were unlikely to be resighted 1 year after infection, with 6 out of 7 individuals that never resighted again compared to 20 out of 63 uninfected individuals and 5 out of 12 individuals in the re-infected category. Collectively, our findings indicate that acute and superficially harmless infection with LPAIV may have indirect effects on individual performance and recruitment in migratory Bewick's swans. Our results also highlight the potential for infection history to play an important role in shaping ecological constraints throughout the annual cycle. PMID- 27252212 TI - Evolutionary Endocrinology of Hormonal Rhythms: Juvenile Hormone Titer Circadian Polymorphism in Gryllus firmus. AB - Daily rhythms for hormonal traits are likely widespread and important aspects of organismal (e.g., life history) adaptation. Yet they remain substantially understudied, especially with respect to variable rhythms within species. The cricket, Gryllus firmus, exhibits a genetically polymorphic circadian rhythm for the blood titer of the key hormone, juvenile hormone (JH). Gryllus firmus is also wing-polymorphic, consisting of a dispersing morph that delays reproduction and a flightless morph with substantially enhanced egg production. JH circadian phenotype strongly covaries with morph type: The blood JH titer is strongly rhythmic in multiple populations artificially-selected for the dispersing morph (LW(f) = long wings with functional flight muscles) and is essentially arrhythmic in populations selected for the SW (short-winged) morph. Association between JH titer cycle and LW(f) morph is also found in natural populations of G. firmus and in several related species in the field. This is one of the very few studies of endocrine titer variation in natural populations of an insect. The morph-specific cycle is underlain by a circadian rhythm in hormone biosynthesis, which in turn is underlain by a rhythm in a brain neuropeptide regulator of JH biosynthesis. The morph-specific JH titer circadian cycle is also strongly correlated with a morph-specific daily rhythm in global gene expression. This is currently the only example of a genetically-variable hormone circadian rhythm in both the laboratory and field that is strongly associated with an ecologically important polymorphism. The extensive information on the underlying causes of the morph specific JH titer rhythm, coupled with the strong association between the JH circadian rhythm and wing polymorphism makes this system in G. firmus an exceptional experimental model to investigate the mechanisms underlying circadian hormonal adaptations. Genetic polymorphism for the JH titer circadian rhythm in G. firmus is discussed in context of circadian rhythms for endocrine traits reported for vertebrates and insects. Consequences of the failure to identify endocrine circadian rhythms on the accuracy of estimation of quantitative-genetic parameters, such as heritability and correlations between hormonal and fitness related traits, are also discussed. PMID- 27252213 TI - Next-Generation Sequencing and the Crustacean Immune System: The Need for Alternatives in Immune Gene Annotation. AB - Next-generation sequencing has been a huge benefit to investigators studying non model species. High-throughput gene expression studies, which were once restricted to animals with extensive genomic resources, can now be applied to any species. Transcriptomic studies using RNA-Seq can discover hundreds of thousands of transcripts from any species of interest. The power and limitation of these techniques is the sheer size of the dataset that is acquired. Parsing these large datasets is becoming easier as more bioinformatic tools are available for biologists without extensive computer programming expertise. Gene annotation and physiological pathway tools such as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology enable the application of the vast amount of information acquired from model organisms to non-model species. While noble in nature, utilization of these tools can inadvertently misrepresent transcriptomic data from non-model species via annotation omission. Annotation followed by molecular pathway analysis highlights pathways that are disproportionately affected by disease, stress, or the physiological condition being examined. Problems occur when gene annotation procedures only recognizes a subset, often 50% or less, of the genes differently expressed from a non-model organisms. Annotated transcripts normally belong to highly conserved metabolic or regulatory genes that likely have a secondary or tertiary role, if any at all, in immunity. They appear to be disproportionately affected simply because conserved genes are most easily annotated. Evolutionarily induced specialization of physiological pathways is a driving force of adaptive evolution, but it results in genes that have diverged sufficiently to prevent their identification and annotation through conventional gene or protein databases. The purpose of this manuscript is to highlight some of the challenges faced when annotating crustacean immune genes by using an American lobster (Homarus americanus) transcriptome as an example. Immune genes have evolved rapidly over time, facilitating speciation and adaption to highly divergent ecological niches. Complete and proper annotation of immune genes from invertebrates has been challenging. Modulation of the crustacean immune system occurs in a variety of physiological responses including biotic and abiotic stressors, molting and reproduction. A simple method for the identification of a greater number of potential immune genes is proposed, along with a short introductory primer on crustacean immune response. The intended audience is not the advanced bioinformatic user, but those investigating physiological responses who require rudimentary understanding of crustacean immunological principles, but where immune gene regulation is not their primary interest. PMID- 27252214 TI - The Baculum was Gained and Lost Multiple Times during Mammalian Evolution. AB - The rapid evolution of male genitalia is a nearly ubiquitous pattern across sexually reproducing organisms, likely driven by the evolutionary pressures of male-male competition, male-female interactions, and perhaps pleiotropic effects of selection. The penis of many mammalian species contains a baculum, a bone that displays astonishing morphological diversity. The evolution of baculum size and shape does not consistently correlate with any aspects of mating system, hindering our understanding of the evolutionary processes affecting it. One potential explanation for the lack of consistent comparative results is that the baculum is not actually a homologous structure. If the baculum of different groups evolved independently, then the assumption of homology inherent in comparative studies is violated. Here, we specifically test this hypothesis by modeling the presence/absence of bacula of 954 mammalian species across a well established phylogeny and show that the baculum evolved a minimum of nine times, and was lost a minimum of ten times. Three different forms of bootstrapping show our results are robust to species sampling. Furthermore, groups with a baculum show evidence of higher rates of diversification. Our study offers an explanation for the inconsistent results in the literature, and provides insight into the evolution of this remarkable structure. PMID- 27252215 TI - Intromittent Organ Morphology and Biomechanics: Defining the Physical Challenges of Copulation. AB - Intromittent organs-structures that place gametes into a mate for internal fertilization-evolved many times within the animal kingdom, and are remarkable for their extravagant morphological diversity. Some taxa build intromittent organs from tissues with reproductive system antecedents, but others copulate with modified fins, tentacles, or legs: anatomically, these structures can include combinations of stiff tissues, extensible tissues, and muscle. Their mechanical behavior during copulation is also diverse: males in some taxa reorient or protrude genital tissues, others inflate them and change their shape, while still other taxa combine these strategies. For these animals, the ability to ready an intromittent organ for copulation and physically interact with a mate's genital tissues is critical to reproductive success, and may be tied to aspects of postcopulatory selection such as sperm competition and sexual conflict. But we know little about their mechanical behavior during copulation. This review surveys mechanical strategies that animals may use for intromittent organ function during intromission and copulation, and discusses how they may perform when their tissues experience stresses in tension, compression, bending, torsion, or shear. PMID- 27252216 TI - Beyond the Eye: Molecular Evolution of Extraocular Photoreception. AB - The molecular mechanisms used by biological systems to detect light are diverse, with at least 10 classes of photosensor proteins and additional photosensitive domains characterized. At least six of these protein classes-Type I microbial opsins, Type II animal opsins, cryptochromes, gustatory-related receptors (GRRs), transient receptor potential A1 ion channels, and euglenoid photoactivated adenylyl cylases-can be considered as playing a role in extraocular systems (e.g., expressed outside of the eye in organisms with a visual system). These six classes of extraocular photosensor proteins consist of four broad groups: (1) seven transmembrane proteins, (2) cryptochromes, (3) ion channels, and (4) adenylyl cyclases. The light-driven functions of these extraocular photoreceptors are diverse, ranging from circadian entrainment to phototactic behavior. There are surprising similarities in structural motifs, with at least three independent families-the GRRs and Types I and II opsins-evolving a seven transmembrane helical tertiary structure for light sensing. When considering all of the photosensitive proteins, particularly those in microbial lineages, an image of evolutionary flexibility is emerging, with examples of fusion proteins from multiple types of photosensors and photosensitive domains shared among diverse arrays of proteins. In general, large questions remain for most of these photosensor proteins about exactly how the protein evolved light sensitivity, how light interacts with the protein, and how the photosensitive protein is transducing the signal. PMID- 27252217 TI - Applying the Power of Transcriptomics: Understanding Male Sexual Development in Decapod Crustacea. AB - The decapod Crustacea are the most species-rich order of the Crustacea and include some of the most charismatic and highly valued commercial species. Thus the decapods draw a significant research interest in relation to aquaculture, as well as gaining a broader understanding of these species' biology. However, the diverse physiology of the group considered with the lack of a model species have presented an obstacle for comparative analyses. In reflection of this, the recent integration of comparative transcriptomics has rapidly advanced our understanding of key regulatory pathways and developmental phenomena, an example being our understanding of sexual development. We discuss our work in the Eastern spiny lobster, Sagmariasus verreauxi, in the context of what is currently known about male sexual development in the decapods, highlighting the importance of transcriptomic techniques in achieving our recent advancements. We describe the progression made in our understanding of male sexual differentiation and maturation, as mediated by the insulin-like androgenic gland hormone (IAG), integrating the role of regulatory binding proteins (IGFBPs), a tyrosine kinase insulin receptor (TKIR), as well as the upstream effect of neuroendocrine hormones (GIH and MIH). We then consider the less well understood mechanism of male sex determination, with an emphasis on what we believe to be the key regulatory factors, the Dsx- and mab-3-related transcription factors (Dmrts). Finally, we discuss the function of the antennal gland (AnG) in sexual development, relating to the emergence of male-biased upregulation in the AnG in later sexual maturation and the sexually dimorphic expression of two key genes Sv TKIR and Sv-Dmrt1 We then present the AnG as a case study to illustrate how comparative transcriptomic techniques can be applied to guide preliminary analyses, like the hypothesis that the AnG may function in pheromone biosynthesis. In summary, we describe the power of transcriptomics in facilitating the progress made in our understanding of male sexual development, as illustrated by the commercial decapod species, S. verreauxi Considering future directions, we suggest that the integration of multiple omics-based techniques offers the most powerful tool to ensure we continue to piece together the biology of the important group of decapod Crustacea. PMID- 27252218 TI - Photoreception in Phytoplankton. AB - In many species of phytoplankton, simple photoreceptors monitor ambient lighting. Photoreceptors provide a number of selective advantages including the ability to assess the time of day for circadian rhythms, seasonal changes, and the detection of excessive light intensities and harmful UV light. Photoreceptors also serve as depth gauges in the water column for behaviors such as diurnal vertical migration. Photoreceptors can be organized together with screening pigment into visible eyespots. In a wide variety of motile phytoplankton, including Chlamydomonas, Volvox, Euglena, and Kryptoperidinium, eyespots are light sensitive organelles residing within the cell. Eyespots are composed of photoreceptor proteins and typically red to orange carotenoid screening pigments. This association of photosensory pigment with screening pigment allows for detection of light directionality, needed for light-guided behaviors such as positive and negative phototaxis. In Chlamydomonas, the eyespot is located in the chloroplast and Chlamydomonas expresses a number of photosensory pigments including the microbial channelrhodopsins (ChR1 and ChR2). Dinoflagellates are unicellular protists that are ecologically important constituents of the phytoplankton. They display a great deal of diversity in morphology, nutritional modes and symbioses, and can be photosynthetic or heterotrophic, feeding on smaller phytoplankton. Dinoflagellates, such as Kryptoperidinium foliaceum, have eyespots that are used for light-mediated tasks including phototaxis. Dinoflagellates belonging to the family Warnowiaceae have a more elaborate eye. Their eye-organelle, called an ocelloid, is a large, elaborate structure consisting of a focusing lens, highly ordered retinal membranes, and a shield of dark pigment. This complex eye-organelle is similar to multicellular camera eyes, such as our own. Unraveling the molecular makeup, structure and function of dinoflagellate eyes, as well as light-guided behaviors in phytoplankton can inform us about the selective forces that drove evolution in the important steps from light detection to vision. We show here that the evolution from simple photoreception to vision seems to have independently followed identical paths and principles in phytoplankton and animals, significantly strengthening our understanding of this important biological process. PMID- 27252219 TI - Thermal Change and the Dynamics of Multi-Host Parasite Life Cycles in Aquatic Ecosystems. AB - Altered thermal regimes associated with climate change are impacting significantly on the physical, chemical, and biological characteristics of the Earth's natural ecosystems, with important implications for the biology of aquatic organisms. As well as impacting the biology of individual species, changing thermal regimes have the capacity to mediate ecological interactions between species, and the potential for climate change to impact host-parasite interactions in aquatic ecosystems is now well recognized. Predicting what will happen to the prevalence and intensity of infection of parasites with multiple hosts in their life cycles is especially challenging because the addition of each additional host dramatically increases the potential permutations of response. In this short review, we provide an overview of the diverse routes by which altered thermal regimes can impact the dynamics of multi-host parasite life cycles in aquatic ecosystems. In addition, we examine how experimentally amenable host parasite systems are being used to determine the consequences of changing environmental temperatures for these different types of mechanism. Our overarching aim is to examine the potential of changing thermal regimes to alter not only the biology of hosts and parasites, but also the biology of interactions between hosts and parasites. We also hope to illustrate the complexity that is likely to be involved in making predictions about the dynamics of infection by multi-host parasites in thermally challenged aquatic ecosystems. PMID- 27252220 TI - Do Hormones, Telomere Lengths, and Oxidative Stress form an Integrated Phenotype? A Case Study in Free-Living Tree Swallows. AB - Synopsis All organisms must anticipate and balance energetic demands and available resources in order to maximize fitness. As hormones coordinate many interactions between an organism's internal condition and the external environment, they may be key in mediating the allocation of resources to meet these demands. However, given that individuals differ considerably in how they react to changes in energetic demand, we asked whether variations in endocrine traits also correspond with life history variation. We tested whether natural variation in glucocorticoid hormone levels, oxidative stress measurements, and condition related to reproductive effort in a free-living songbird, the tree swallow, Tachycineta bicolor We then tested whether any of these traits predicted the probability of a particular individual's return to the local population in the following two years, an indicator of survival in this philopatric species. We found that males and females with longer telomeres had lighter nestlings. Moreover, individuals with lower plasma antioxidant capacity and higher reactive oxygen metabolites (i.e., greater oxidative stress) were less likely to return to the population. However, none of these traits were related to glucocorticoid levels. Our findings suggest a trade-off between reproduction and survival, with individuals with shorter telomeres having heavier nestlings but potentially paying a cost in terms of higher oxidative stress and lower survival. Interestingly, the evidence of this trade-off was unrelated to natural variation in glucocorticoids. PMID- 27252221 TI - Evolution and Function of the Insulin and Insulin-like Signaling Network in Ectothermic Reptiles: Some Answers and More Questions. AB - The insulin and insulin-like signaling (IIS) molecular network regulates cellular growth and division, and influences organismal metabolism, growth and development, reproduction, and lifespan. As a group, reptiles have incredible diversity in the complex life history traits that have been associated with the IIS network, yet the research on the IIS network in ectothermic reptiles is sparse. Here, we review the IIS network and synthesize what is known about the function and evolution of the IIS network in ectothermic reptiles. The primary hormones of this network-the insulin-like growth factors 1 and 2 (IGFs) likely function in reproduction in ectothermic reptiles, but the precise mechanisms are unclear, and likely range from influencing mating and ovulation to maternal investment in embryonic development. In general, plasma levels of IGF1 increase with food intake in ectothermic reptiles, but the magnitude of the response to food varies across species or populations and the ages of animals. Long-term temperature treatments as well as thermal stress can alter expression of genes within the IIS network. Although relatively little work has been done on IGF2 in ectothermic reptiles, IGF2 is consistently expressed at higher levels than IGF1 in juvenile ectothermic reptiles. Furthermore, in contrast to mammals that have genetic imprinting that silences the maternal IGF2 allele, in reptiles IGF2 is bi allelically expressed (based on findings in chickens, a snake, and a lizard). Evolutionary analyses indicate some members of the IIS network are rapidly evolving across reptile species, including IGF1, insulin (INS), and their receptors. In particular, IGF1 displays extensive nucleotide variation across lizards and snakes, which suggests that its functional role may vary across this group. In addition, genetic variation across families and populations in the response of the IIS network to environmental conditions illustrates that components of this network may be evolving in natural populations. The diversity in reproductive physiology, metabolic plasticity, and lifespan among reptiles makes the study of the IIS network in this group a potentially rich avenue for insight into the evolution and function of this network. The field would benefit from future studies that discern the respective functions of IGF1 and IGF2 and how these functions vary across taxa, perfecting additional assays for measuring IIS components, and determining the role of IIS in different tissues. PMID- 27252223 TI - Endocrine Control of Exaggerated Trait Growth in Rhinoceros Beetles. AB - Juvenile hormone (JH) is a key insect growth regulator frequently involved in modulating phenotypically plastic traits such as caste determination in eusocial species, wing polymorphisms in aphids, and mandible size in stag beetles. The jaw morphology of stag beetles is sexually-dimorphic and condition-dependent; males have larger jaws than females and those developing under optimum conditions are larger in overall body size and have disproportionately larger jaws than males raised under poor conditions. We have previously shown that large males have higher JH titers than small males during development, and ectopic application of fenoxycarb (JH analog) to small males can induce mandibular growth similar to that of larger males. What remains unknown is whether JH regulates condition dependent trait growth in other insects with extreme sexually selected structures. In this study, we tested the hypothesis that JH mediates the condition-dependent expression of the elaborate horns of the Asian rhinoceros beetle, Trypoxylus dichotomus. The sexually dimorphic head horn of this beetle is sensitive to nutritional state during larval development. Like stag beetles, male rhinoceros beetles receiving copious food produce disproportionately large horns for their body size compared with males under restricted diets. We show that JH titers are correlated with body size during the late feeding and early prepupal periods, but this correlation disappears by the late prepupal period, the period of maximum horn growth. While ectopic application of fenoxycarb during the third larval instar significantly delayed pupation, it had no effect on adult horn size relative to body size. Fenoxycarb application to late prepupae also had at most a marginal effect on relative horn size. We discuss our results in context of other endocrine signals of condition-dependent trait exaggeration and suggest that different beetle lineages may have co-opted different physiological signaling mechanisms to achieve heightened nutrient-sensitive weapon growth. PMID- 27252222 TI - A Bird's Eye View of Influenza A Virus Transmission: Challenges with Characterizing Both Sides of a Co-Evolutionary Dynamic. AB - In nature, wild birds and influenza A viruses (IAV) are continually co-evolving, locked into a back-and-forth of resistance and conquest that has approached a stable equilibrium over time. This co-evolutionary relationship between bird host and IAV may appear stable at the organismal level, but is highly dynamic at the molecular level manifesting in a constant trade-off between transmissibility and virulence of the virus. Characterizing both sides of the host-virus dynamic has presented a challenge for ecologists and virologists alike, despite the potential for this approach to provide insights into which conditions destabilize the equilibrium state resulting in outbreaks or mortality of hosts in extreme cases. The use of different methods that are either host-centric or virus-centric has made it difficult to reconcile the disparate fields of host ecology and virology for investigating and ultimately predicting wild bird-mediated transmission of IAV. This review distills some of the key lessons learned from virological and ecological studies and explores the promises and pitfalls of both approaches. Ultimately, reconciling ecological and virological approaches hinges on integrating scales for measuring host-virus interactions. We argue that prospects for finding common scales for measuring wild bird-influenza dynamics are improving due to advances in genomic sequencing, host-tracking technology and remote sensing data, with the unit of time (months, year, or seasons) providing a starting point for crossover. PMID- 27252224 TI - Suchian Feeding Success at the Interface of Ontogeny and Macroevolution. AB - There have been a number of attempts to explain how crocodylian bite-force performance covaries with cranial form and diet. However, the mechanics and morphologies of crocodylian jaws have thus far remained incongruent with data on their performance and evolution. For example, it is largely assumed that the functional anatomy and performance of adults tightly fits the adult niche. At odds with this precept are groups with resource-dependent growth, whose juvenile stages undergo shifts in mass, morphology, and resource usage to overcome strong selection related to issues of small body size, as compared to adults. Crocodylians are an example of such a group. As living suchians, they also have a long and fossil-rich evolutionary history, characterized by analogous increases in body size, diversifications in rostrodental form, and shifts in diet. Here we use biomechanical and evolutionary modeling techniques to study the development and evolution of the suchian feeding apparatus and to formally assess the impact of potential ontogenetic-evolutionary parallels on clade dynamics. We show that patterns of ontogenetic and evolutionary bite-force changes exhibit inverted patterns of heterochrony, indicating that early ontogenetic trends are established as macroevolutionary patterns within Neosuchia, prior to the origin of Eusuchia. Although selection can act on any life-history stage, our findings suggest that selection on neonates and juveniles, in particular, can contribute to functionally important morphologies that aid individual and clade success without being strongly tied to their adult niche. PMID- 27252225 TI - Modeling vector-borne disease risk in migratory animals under climate change. AB - Recent theory suggests that animals that migrate to breed at higher latitudes may benefit from reduced pressure from natural enemies, including pathogens ("migratory escape"), and that migration itself weeds out infected individuals and lowers infection prevalence ("migratory culling"). The distribution and activity period of arthropod disease vectors in temperate regions is expected to respond rapidly to climate change, which could reduce the potential for migratory escape. However, climate change could have the opposite effect of reducing transmission if differential responses in the phenology and distribution of migrants and disease vectors reduce their overlap in space and time. Here we outline a simple modeling framework for exploring the influence of climate change on vector-borne disease dynamics in a migratory host. We investigate two scenarios under which pathogen transmission dynamics might be mediated by climate change: (1) vectors respond more rapidly than migrants to advancing phenology at temperate breeding sites, causing peak susceptible host density and vector emergence to diverge ("migratory mismatch") and (2) reduced migratory propensity allows increased nonbreeding survival of infected hosts and larger breeding-site epidemics (loss of migratory culling, here referred to as "sedentary amplification"). Our results highlight the need for continued surveillance of climate-induced changes to migratory behavior and vector activity to predict pathogen prevalence and its impacts on migratory animals. PMID- 27252226 TI - Pulmonary Hypertensive Crisis on Induction of Anesthesia. AB - Anesthesia for lung transplantation remains one of the highest risk surgeries in the domain of the cardiothoracic anesthesiologist. End-stage lung disease, pulmonary hypertension, and right heart dysfunction as well as other comorbid disease factors predispose the patient to cardiovascular, respiratory and metabolic dysfunction during general anesthesia. Perhaps the highest risk phase of surgery in the patient with severe pulmonary hypertension is during the induction of anesthesia when the removal of intrinsic sympathetic tone and onset of positive pressure ventilation can decompensate a severely compromised cardiovascular system. Severe hypotension, cardiac arrest, and death have been reported previously. Here we present 2 high-risk patients for lung transplantation, their anesthetic induction course, and outcomes. We offer suggestions for the safe management of anesthetic induction to mitigate against hemodynamic and respiratory complications. PMID- 27252227 TI - Fabrication and evaluation of electrohydrodynamic jet 3D printed polycaprolactone/chitosan cell carriers using human embryonic stem cell-derived fibroblasts. AB - Biological function of adherent cells depends on the cell-cell and cell-matrix interactions in three-dimensional space. To understand the behavior of cells in 3D environment and their interactions with neighboring cells and matrix requires 3D culture systems. Here, we present a novel 3D cell carrier scaffold that provides an environment for routine 3D cell growth in vitro We have developed thin, mechanically stable electrohydrodynamic jet (E-jet) 3D printed polycaprolactone and polycaprolactone/Chitosan macroporous scaffolds with precise fiber orientation for basic 3D cell culture application. We have evaluated the application of this technology by growing human embryonic stem cell-derived fibroblasts within these 3D scaffolds. Assessment of cell viability and proliferation of cells seeded on polycaprolactone and polycaprolactone/Chitosan 3D-scaffolds show that the human embryonic stem cell-derived fibroblasts could adhere and proliferate on the scaffolds over time. Further, using confocal microscopy we demonstrate the ability to use fluorescence-labelled cells that could be microscopically monitored in real-time. Hence, these 3D printed polycaprolactone and polycaprolactone/Chitosan scaffolds could be used as a cell carrier for in vitro 3D cell culture-, bioreactor- and tissue engineering-related applications in the future. PMID- 27252229 TI - Aortic coarctation associated with thrombosis mimicking interrupted arch. PMID- 27252228 TI - Epileptiform activity and spreading depolarization in the blood-brain barrier disrupted peri-infarct hippocampus are associated with impaired GABAergic inhibition and synaptic plasticity. AB - Peri-infarct opening of the blood-brain barrier may be associated with spreading depolarizations, seizures, and epileptogenesis as well as cognitive dysfunction. We aimed to investigate the mechanisms underlying neural network pathophysiology in the blood-brain barrier-dysfunctional hippocampus. Photothrombotic stroke within the rat neocortex was associated with increased intracranial pressure, vasogenic edema, and peri-ischemic blood-brain barrier dysfunction that included the ipsilateral hippocampus. Intrahippocampal recordings revealed electrographic seizures within the first week in two-thirds of animals, accompanied by a reduction in gamma and increase in theta frequency bands. Synaptic interactions were studied in parasagittal hippocampal slices at 24 h and seven days post stroke. Field potential recordings in CA1 and CA3 uncovered multiple population spikes, epileptiform episodes, and spreading depolarizations at 24 h. Input output analysis revealed that fEPSP-spike coupling was significantly enhanced at seven days. In addition, CA1 feedback and feedforward inhibition were diminished. Slices generating epileptiform activity at seven days revealed impaired bidirectional long-term plasticity following high and low-frequency stimulation protocols. Microarray and PCR data confirmed changes in expression of astrocyte related genes and suggested downregulation in expression of GABAA-receptor subunits. We conclude that blood-brain barrier dysfunction in the peri-infarct hippocampus is associated with early disinhibition, hyperexcitability, and abnormal synaptic plasticity. PMID- 27252230 TI - Emphysematous aortitis leading to esophagopleural fistula. AB - Emphysematous aortitis is a form of septic aortitis. It is a rare disease with a high mortality rate, necessitating prompt diagnosis and aggressive treatment. We present the computed tomography features of emphysematous aortitis leading to esophageal rupture and esophageal-pleural fistula in a 76-year-old female with rheumatoid arthritis. PMID- 27252231 TI - Dendriform pulmonary ossification in a patient with mucoepidermoid carcinoma. AB - Dendriform pulmonary ossification is a chronic process characterized by the presence of heterotopic bone within the interstitium and alveolar walls. It usually occurs in the setting of chronic inflammation. We report an unusual case of a 54-year-old man with a history of relapsing Hodgkin lymphoma who was diagnosed with concomitant mucoepidermoid pulmonary carcinoma and dendriform ossifications. The radiological features were initially misinterpreted as post radiation pulmonary fibrosis and bronchiectasis. The diagnosis was finally established after considering both the radiological and pathological findings. Dendriform pulmonary ossification is an under-recognized disease that should be considered in the differential diagnosis of lung chronic diseases. PMID- 27252232 TI - Idelalisib in the management of lymphoma. AB - Inhibition of the phosphatidylinositol-3-kinase (PI3K) pathway as an anticancer therapeutic strategy was realized with the approval of the orally bioavailable small molecule PI3Kdelta inhibitor idelalisib. In this focused review, we highlight the rationale for targeting the pathway in lymphomas, provide a brief summary of the preclinical data, and describe the clinical experience with this agent in patients with lymphoma. We describe some of the idiosyncratic toxicities of this agent, some of the mechanisms of resistance, and some of the ongoing combination strategies. PMID- 27252234 TI - Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration. AB - Several lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here, we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype, and exhibit enhanced capacity for T-cell activation and superior immune synapse formation when compared with paired peripheral blood (PB) samples. LN-derived CLL cells manifest a proliferative, CXCR4(dim)CD5(bright) phenotype compared with those in the PB and higher expression of T-cell activation molecules including CD80, CD86, and HLA-D-related (DR). In addition, LN-CLL cells have higher expression of alpha4beta1 (CD49d) which, as well as being a co stimulatory molecule, is required for CLL cells to undergo transendothelial migration (TEM) and enter the proliferation centers of the LNs. Using an in vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4(dim)CD5(bright) with higher CD49d, CD80, CD86, and HLA-DR compared with those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49d(hi) CLL cells showed an enhanced capacity to activate T cells compared with CD49d(lo) subpopulations from the same patient. Thus, although PB-CLL cells have a reduced capacity to form immune synapses and activate CD4(+) T cells, this was not the case for LN CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunologic function is not only modulated by microenvironmental interactions but is also a feature of a subpopulation of PB CLL cells that are primed for lymphoid tissue homing and interaction with T cells. PMID- 27252233 TI - Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice. AB - Thrombin-mediated proteolysis is central to hemostatic function but also plays a prominent role in multiple disease processes. The proteolytic conversion of fII to alpha-thrombin (fIIa) by the prothrombinase complex occurs through 2 parallel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermediate, meizothrombin (fIIa(MZ)). FIIa(MZ) has distinct catalytic properties relative to fIIa, including diminished fibrinogen cleavage and increased protein C activation. Thus, fII activation may differentially influence hemostasis and disease depending on the pathway of activation. To determine the in vivo physiologic and pathologic consequences of restricting thrombin generation to fIIa(MZ), mutations were introduced into the endogenous fII gene, resulting in expression of prothrombin carrying 3 amino acid substitutions (R157A, R268A, and K281A) to limit activation events to yield only fIIa(MZ) Homozygous fII(MZ) mice are viable, express fII levels comparable with fII(WT) mice, and have reproductive success. Although in vitro studies revealed delayed generation of fIIa(MZ) enzyme activity, platelet aggregation by fII(MZ) is similar to fII(WT) Consistent with prior analyses of human fIIa(MZ), significant prolongation of clotting times was observed for fII(MZ) plasma. Adult fII(MZ) animals displayed significantly compromised hemostasis in tail bleeding assays, but did not demonstrate overt bleeding. More notably, fII(MZ) mice had 2 significant phenotypic advantages over fII(WT) animals: protection from occlusive thrombosis after arterial injury and markedly diminished metastatic potential in a setting of experimental tumor metastasis to the lung. Thus, these novel animals will provide a valuable tool to assess the role of both fIIa and fIIa(MZ) in vivo. PMID- 27252235 TI - Public Opinion Regarding Financial Incentives to Engage in Advance Care Planning and Complete Advance Directives. AB - BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) recently instituted physician reimbursements for advance care planning (ACP) discussions with patients. AIM: To measure public support for similar programs. DESIGN: Cross sectional online and in-person surveys. SETTING/PARTICIPANTS: English-speaking adults recruited at public parks in Philadelphia, Pennsylvania, from July to August 2013 and online through survey sampling international Web-based recruitment platform in July 2015. Participants indicated support for 6 programs designed to increase advance directive (AD) completion or ACP discussion using 5 point Likert scales. Participants also indicated how much money (US$0-US$1000) was appropriate to incentivize such behaviors, compared to smoking cessation or colonoscopy screening. RESULTS: We recruited 883 participants: 503 online and 380 in-person. The status quo of no systematic approach to motivate AD completion was supported by 67.0% of participants (63.9%-70.1%). The most popular programs were paying patients to complete ADs (58.0%; 54.5%-61.2%) and requiring patients to complete ADs or declination forms for health insurance (54.1%; 50.8%-57.4%). Participants more commonly supported paying patients to complete ADs than paying physicians whose patients complete ADs (22.6%; 19.8%-25.4%) or paying physicians who document ACP discussions (19.1%; 16.5%-21.7%; both P < .001). Participants supported smaller payments for AD completion and ACP than for obtaining screening colonoscopies or stopping smoking. CONCLUSIONS: Americans view payments for AD completion or ACP more skeptically than for other health behaviors and prefer that such payments go to patients rather than physicians. The current CMS policy of reimbursing physicians for ACP conversations with patients was the least preferred of the programs evaluated. PMID- 27252237 TI - Sixty seconds on . . . Tamiflu. PMID- 27252236 TI - TransRate: reference-free quality assessment of de novo transcriptome assemblies. AB - TransRate is a tool for reference-free quality assessment of de novo transcriptome assemblies. Using only the sequenced reads and the assembly as input, we show that multiple common artifacts of de novo transcriptome assembly can be readily detected. These include chimeras, structural errors, incomplete assembly, and base errors. TransRate evaluates these errors to produce a diagnostic quality score for each contig, and these contig scores are integrated to evaluate whole assemblies. Thus, TransRate can be used for de novo assembly filtering and optimization as well as comparison of assemblies generated using different methods from the same input reads. Applying the method to a data set of 155 published de novo transcriptome assemblies, we deconstruct the contribution that assembly method, read length, read quantity, and read quality make to the accuracy of de novo transcriptome assemblies and reveal that variance in the quality of the input data explains 43% of the variance in the quality of published de novo transcriptome assemblies. Because TransRate is reference-free, it is suitable for assessment of assemblies of all types of RNA, including assemblies of long noncoding RNA, rRNA, mRNA, and mixed RNA samples. PMID- 27252238 TI - Prognostic value of body mass index and change in body weight in postoperative outcomes of lung cancer surgery. AB - OBJECTIVES: Nutritional status is associated with an effect on oncological outcomes. However, the effect of nutritional status on postoperative survival in lung cancer has not been well studied. We retrospectively analysed and evaluated the effect of preoperative body mass index (BMI) and changes in body weight on postoperative outcomes of lung cancer surgery. METHODS: A total of 1311 patients with non-small-cell lung cancer who underwent surgery between January 2001 and December 2011 were included in this study. Preoperative body weight at 4-12 weeks prior to surgery was obtained in 737 patients and the ratio of change in body weight was calculated. RESULTS: The patients were classified into four groups as follows: underweight (BMI < 18.5), normal weight (BMI from >=18.5 to <25), overweight (BMI from >=25 to <30) and obese (BMI >= 30). Postoperative survival curves of the BMI groups showed that the underweight group had a poorer prognosis than the other groups, especially for disease-free survival (DFS) (P = 0.03). Univariate and adjusted survival analyses using Cox's proportional hazards regression model showed that low BMI was a significantly poor prognostic factor in overall survival (OS) (P = 0.03 and P = 0.02, respectively) and DFS (P < 0.01 and P < 0.01, respectively). Among the BMI groups, the underweight group had a significant worse prognosis than the other groups for DFS in univariate and adjusted analyses (P = 0.04 and P < 0.01, respectively). With regard to changes in body weight, patients with a body weight loss of 3.7% or greater had a significantly poorer prognosis for OS and DFS in univariate analysis and for DFS in adjusted analyses compared with the other patients. Regarding short-term outcomes, the weight loss group had a significantly longer postoperative hospital stay than the non-weight loss group (P = 0.02) and postoperative 90-day mortality was significantly lower in the normal weight group than in the underweight group (P = 0.03). CONCLUSIONS: Low BMI and significant body weight loss before surgery have a negative effect on surgical outcomes for patients with non-small-cell lung cancer. PMID- 27252239 TI - Impact of donor age on cardiac transplantation outcomes and on cardiac function. AB - OBJECTIVES: Although the impact of older donors on heart transplant outcomes has been previously published, the survival results are conflicting. We herein analyse the impact of older donors on transplant survival and myocardial function. METHODS: The records of the patients who underwent heart transplant at Baylor University Medical Center at Dallas from November 2012 until March 2015 were reviewed and the data were extracted. The heart recipients were divided into two groups based on donors age; 50 years of age was the division point. The two groups were compared with regard to the following transplant outcomes: in hospital and 1-year survival, severe (3R) rejection, primary graft dysfunction, myocardial performance as reflected by the inotropic score, left ventricular ejection fraction, intensive care unit and overall length of stay. RESULTS: Anoxia was more common cause of death in younger donors (43.9%), whereas intracranial bleeding was more frequent in older donors (48.1%, P = 0.016). The in-hospital survival and 1-year survival were the same between the two groups. Additionally, cardiac transplantation from older donors was not associated with higher incidence of graft dysfunction, higher inotropic support score, longer intensive care unit and total hospital length of stay or more frequent severe rejection episodes. The left ventricular ejection fraction was similar between the two groups. CONCLUSIONS: Heart transplant from older donors is not associated with lower in-hospital and mid-term survival if donors are carefully selected; furthermore, the graft function is comparable. The use of hearts from donors older than 50 years of age can be expanded beyond critically ill recipients in carefully selected recipients. PMID- 27252240 TI - Transcatheter CoreValve implantation for aortic regurgitation in a Jehovah's witness with prior aortic dissection. AB - Indications for transcatheter valve implantation have been extended to treat native valve aortic regurgitation in case of disproportionate risk for open surgery. Transcatheter aortic valves are also an attractive alternative in patients who refuse blood transfusions. We report the successful off-label implantation of a self-expandable transcatheter valve in a Jehovah's Witness with prior replacement of the ascending aorta for Type A dissection, residual severe aortic regurgitation and refractory heart failure. PMID- 27252241 TI - Does positron emission tomography/computed tomography aid the diagnosis of prosthetic valve infective endocarditis? AB - A best evidence topic was constructed according to a structured protocol. The question addressed was whether (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) aids the diagnosis of prosthetic valve endocarditis (PVE)? A total of 107 publications were found using the reported search, of which 6 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The reported outcome of all studies was a final diagnosis of confirmed endocarditis on follow-up. All the six studies were non-randomized, single-centre, observational studies and thus represented level 3 evidence. The diagnostic capability of PET/CT for PVE was compared with that of the modified Duke Criteria and echocardiography, and reported in terms of sensitivity, specificity and positive and negative predictive values. All studies demonstrated an increased sensitivity for the diagnosis of PVE when PET/CT was combined with the modified Duke Criteria on admission. A higher SUVmax on PET was found to be significantly associated with a confirmed diagnosis of endocarditis and an additional diagnostic benefit of PET/CT angiography over conventional PET/non-enhanced CT is reported due to improved anatomical resolution. However, PET/CT was found to be unreliable in the early postoperative period due to its inability to distinguish between infection and residual postoperative inflammatory changes. PET/CT was also found to be poor at diagnosing cases of native valve endocarditis. We conclude that PET/CT aids in the diagnosis of PVE when combined with the modified Duke Criteria on admission by increasing the diagnostic sensitivity. The diagnostic ability of PET/CT can be potentiated by the use of PET/CTA; however, its use may be unreliable in the early postoperative period or in native valve endocarditis. PMID- 27252242 TI - Controversial 999 pilot ambulance trust chief executive resigns. PMID- 27252243 TI - Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. AB - We evaluated the differences in major markers of cardiovascular (CV) risk between inflammatory bowel diseases (IBDs) and controls by a systematic review and a meta analysis. We searched PubMed, EMBASE, and Cochrane databases for literature comparing CV risk markers in IBDs and controls. The overall mean carotid intima media thickness (CIMT), flow-mediated dilation (FMD%), and carotid-femoral pulse wave velocity (cfPWV) difference between patients with IBDs and control groups were calculated. Twenty-eight studies were included in the meta-analysis, including 16 studies with data on CIMT, 7 studies reporting FMD%, and 9 studies on cfPWV. Compared to controls, patients with IBDs showed significantly higher CIMT (standardized mean difference [ SMD]: 0.534 mm; 95% confidence interval [CI], 0.230 to 0.838; P = .001), significantly lower FMD% ( SMD, -0.721%; 95% CI, -1.020 to -0.421; P < .0001), and significantly increased cfPWV ( SMD, 0.849; 95% CI, 0.589 to 1.110; P < .0001). When analyzing subgroups with ulcerative colitis and Crohn disease (CD), all results were still significant except CIMT in CD. Our findings support the current evidence for an elevated CV burden in patients with IBD and support the clinical utility of markers of subclinical atherosclerosis in the management of these patients. PMID- 27252244 TI - Arterial Access in Patients With De Novo Acute Coronary Syndrome Undergoing Coronary Angiography. AB - Bleeding is a major limitation of antithrombotic therapy among invasively managed patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACSs). Randomized clinical trials have generally failed to favor either the femoral or the radial arterial approach for coronary angiography or intervention in NSTE ACS. In 561 hospitalized patients with a new diagnosis of NSTE-ACS referred for coronary angiography, 364 and 197 patients underwent the femoral and the radial approach, respectively. Femoral and radial access did not differ in bleeding complications in the first 72 hours (8 of 364 or 2.2% vs 8 of 197 or 4.1%, P = .21), duration of hospitalization (4.67 +/- 5.02 vs 4.51 +/- 4.81, P = .28) nor in-hospital mortality (0.8% vs 0.5%, P = .67). Contrast volume was higher for femoral versus radial cases (204 +/- 119 vs 168 +/- 104, P < .001). In patients with de novo NSTE-ACS without prior cardiac bypass, radial and femoral arterial access did not differ in instances of bleeding within the first 72 hours postoperatively, length of hospital stay, or in-hospital mortality. Less contrast was used in radial cases, which may represent an advantage for patients with renal insufficiency. PMID- 27252245 TI - Telehealth for patients at high risk of cardiovascular disease: pragmatic randomised controlled trial. AB - OBJECTIVE: To assess whether non-clinical staff can effectively manage people at high risk of cardiovascular disease using digital health technologies. DESIGN: Pragmatic, multicentre, randomised controlled trial. SETTING: 42 general practices in three areas of England. PARTICIPANTS: Between 3 December 2012 and 23 July 2013 we recruited 641 adults aged 40 to 74 years with a 10 year cardiovascular disease risk of 20% or more, no previous cardiovascular event, at least one modifiable risk factor (systolic blood pressure >=140 mm Hg, body mass index >=30, current smoker), and access to a telephone, the internet, and email. Participants were individually allocated to intervention (n=325) or control (n=316) groups using automated randomisation stratified by site, minimised by practice and baseline risk score. INTERVENTIONS: Intervention was the Healthlines service (alongside usual care), comprising regular telephone calls from trained lay health advisors following scripts generated by interactive software. Advisors facilitated self management by supporting participants to use online resources to reduce risk factors, and sought to optimise drug use, improve treatment adherence, and encourage healthier lifestyles. The control group comprised usual care alone. MAIN OUTCOME MEASURES: The primary outcome was the proportion of participants responding to treatment, defined as maintaining or reducing their cardiovascular risk after 12 months. Outcomes were collected six and 12 months after randomisation and analysed masked. Participants were not masked. RESULTS: 50% (148/295) of participants in the intervention group responded to treatment compared with 43% (124/291) in the control group (adjusted odds ratio 1.3, 95% confidence interval 1.0 to 1.9; number needed to treat=13); a difference possibly due to chance (P=0.08). The intervention was associated with reductions in blood pressure (difference in mean systolic -2.7 mm Hg (95% confidence interval -4.7 to -0.6 mm Hg), mean diastolic -2.8 (-4.0 to -1.6 mm Hg); weight -1.0 kg (-1.8 to -0.3 kg), and body mass index -0.4 ( -0.6 to -0.1) but not cholesterol -0.1 (-0.2 to 0.0), smoking status (adjusted odds ratio 0.4, 0.2 to 1.0), or overall cardiovascular risk as a continuous measure (-0.4, -1.2 to 0.3)). The intervention was associated with improvements in diet, physical activity, drug adherence, and satisfaction with access to care, treatment received, and care coordination. One serious related adverse event occurred, when a participant was admitted to hospital with low blood pressure. CONCLUSIONS: This evidence based telehealth approach was associated with small clinical benefits for a minority of people with high cardiovascular risk, and there was no overall improvement in average risk. The Healthlines service was, however, associated with improvements in some risk behaviours, and in perceptions of support and access to care.Trial registration Current Controlled Trials ISRCTN 27508731. PMID- 27252247 TI - A failed welfare state. PMID- 27252246 TI - GLP-1 Agonists in Type 1 Diabetes Mellitus. AB - OBJECTIVE: To review the use of GLP-1 agonists in patients with type 1 diabetes mellitus (T1DM). DATA SOURCES: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed through March 2016 using the search terms glucagon-like peptide 1 (GLP-1) agonists, incretin, liraglutide, exenatide, albiglutide, dulaglutide, type 1 diabetes mellitus STUDY SELECTION AND DATA EXTRACTION: All English-language trials that examined glycemic end points using GLP-1 agonists in humans with T1DM were included. DATA SYNTHESIS: A total of 9 clinical trials examining the use of GLP-1 agonists in T1DM were identified. On average, hemoglobin A1C (A1C) was lower than baseline, with a maximal lowering of 0.6%. This effect was not significant when tested against a control group, with a relative decrease in A1C of 0.1% to 0.2%. In all trials examined, reported hypoglycemia was low, demonstrating no difference when compared with insulin monotherapy. Weight loss was seen in all trials, with a maximum weight loss of 6.4 kg over 24 weeks. Gastrointestinal adverse effects are potentially limiting, with a significant number of patients in trials reporting nausea. CONCLUSION: The use of GLP-1 agonists should be considered in T1DM patients who are overweight or obese and not at glycemic goals despite aggressive insulin therapy; however, tolerability of these agents is a potential concern. Liraglutide has the strongest evidence for use and would be the agent of choice for use in overweight or obese adult patients with uncontrolled T1DM. PMID- 27252248 TI - Association of Eating Behavior With Nutritional Status and Body Composition in Primary School-Aged Children. AB - Problematic eating behaviors during childhood may lead to positive energy balance and obesity. Therefore, this study aims to investigate the association of eating behaviors with nutritional status and body composition in Malaysian children aged 7 to 12 years. A total of 1782 primary schoolchildren were randomly recruited from 6 regions in Malaysia. The multidimensional Children's Eating Behaviour Questionnaire (CEBQ) was reported by parents to determine the 8 different dimensions of eating styles among children. Body mass index (BMI), BMI-for-age Z score, waist circumference, and body fat percentage were assessed. Linear regression analyses revealed that both food responsiveness and desire to drink subscales were positively associated with a child's body adiposity, whereas satiety responsiveness, slowness in eating, and emotional undereating subscales were negatively associated with adiposity (all P < .05). A multidimensional eating style approach based on the CEBQ is needed to promote healthy eating behaviors in order to prevent excessive weight gain and obesity problems among Malaysian children. PMID- 27252250 TI - Protective effects of 1alpha,25-Dihydroxyvitamin D3 on cultured neural cells exposed to catalytic iron. AB - Recent studies have postulated a role for vitamin D and its receptor on cerebral function, and anti-inflammatory, immunomodulatory and neuroprotective effects have been described; vitamin D can inhibit proinflammatory cytokines and nitric oxide synthesis during various neurodegenerative insults, and may be considered as a potential drug for the treatment of these disorders. In addition, iron is crucial for neuronal development and neurotransmitter production in the brain, but its accumulation as catalytic form (Fe(3+)) impairs brain function and causes the dysregulation of iron metabolism leading to tissue damage due to the formation of toxic free radicals (ROS). This research was planned to study the role of vitamin D to prevent iron damage in neuroblastoma BE(2)M17 cells. Mechanisms involved in neurodegeneration, including cell viability, ROS production, and the most common intracellular pathways were studied. Pretreatment with calcitriol (the active form of vitamin D) reduced cellular injury induced by exposure to catalytic iron. PMID- 27252251 TI - Effect of dietary n-3 PUFA supplementation on the muscle transcriptome in older adults. AB - Dietary fish oil-derived n-3 PUFA supplementation can increase muscle mass, reduce oxygen demand during physical activity, and improve physical function (muscle strength and power, and endurance) in people. The results from several studies conducted in animals suggest that the anabolic and performance-enhancing effects of n-3 PUFA are at least in part transcriptionally regulated. The effect of n-3 PUFA therapy on the muscle transcriptome in people is unknown. In this study, we used muscle biopsy samples collected during a recently completed randomized controlled trial that found that n-3 PUFA therapy increased muscle mass and function in older adults to provide a comprehensive assessment of the effect of n-3 PUFA therapy on the skeletal muscle gene expression profile in these people. Using the microarray technique, we found that several pathways involved in regulating mitochondrial function and extracellular matrix organization were increased and pathways related to calpain- and ubiquitin mediated proteolysis and inhibition of the key anabolic regulator mTOR were decreased by n-3 PUFA therapy. However, the effect of n-3 PUFA therapy on the expression of individual genes involved in regulating mitochondrial function and muscle growth, assessed by quantitative RT-PCR, was very small. These data suggest that n-3 PUFA therapy results in small but coordinated changes in the muscle transcriptome that may help explain the n-3 PUFA-induced improvements in muscle mass and function. PMID- 27252253 TI - Stephanie de Giorgio: Hates arrogance and knuckle cracking. PMID- 27252252 TI - Limiting collagen turnover via collagenase-resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension. AB - Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension in which right ventricular (RV) afterload is increased and death typically occurs due to decompensated RV hypertrophy and failure. Collagen accumulation has been implicated in pulmonary artery remodeling, but how it affects RV performance remains unclear. Here, we sought to identify the role of collagen turnover, defined as the balance between collagen synthesis and degradation, in RV structure and function in PAH To do so, we exposed mutant (Col1a1(R/R)) mice, in which collagen type I degradation is impaired such that collagen turnover is reduced, and wild-type (Col1a1(+/+)) littermates to 14 days of chronic hypoxia combined with SUGEN treatment (HySu) to recapitulate characteristics of clinical PAH RV structure and function were measured by echocardiography, RV catheterization, and histology. Despite comparable increases in RV systolic pressure (Col1a1(+/+): 46 +/- 2 mmHg; Col1a1(R/R): 47 +/- 3 mmHg), the impaired collagen degradation in Col1a1(R/R) mice resulted in no RV collagen accumulation, limited RV hypertrophy, and maintained right ventricular-pulmonary vascular coupling with HySu exposure. The preservation of cardiac function in the mutant mice indicates a beneficial role of limited collagen turnover via impaired degradation in RV remodeling in response to chronic pressure overload. Our results suggest novel treatments that reduce collagen turnover may offer a new therapeutic strategy for PAH patients. PMID- 27252254 TI - From autoantibody research to standardized diagnostic assays in the management of human diseases - report of the 12th Dresden Symposium on Autoantibodies. AB - Testing for autoantibodies (AABs) is becoming more and more relevant, not only for diagnosing autoimmune diseases (AIDs) but also for the differentiation of defined AID subtypes with different clinical manifestations, course and prognosis as well as the very early diagnosis for adequate management in the context of personalized medicine. A major challenge to improve diagnostic accuracy is to harmonize or even standardize AAB analyses. This review presents the results of the 12th Dresden Symposium on Autoantibodies that focused on several aspects of improving autoimmune diagnostics. Topics that are addressed include the International Consensus on ANA Patterns (ICAP) and the International Autoantibody Standardization (IAS) initiatives, the optimization of diagnostic algorithms, the description and evaluation of novel disease-specific AABs as well as the development and introduction of novel assays into routine diagnostics. This review also highlights important developments of recent years, most notably the improvement in diagnosing and predicting the course of rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, and of autoimmune neurological, gastrointestinal and liver diseases; the potential diagnostic role of anti-DFS70 antibodies and tumor-associated AABs. Furthermore, some hot topics in autoimmunity regarding disease pathogenesis and management are described. PMID- 27252255 TI - Report on the second International Consensus on ANA Pattern (ICAP) workshop in Dresden 2015. AB - The second meeting for the International Consensus on Antinuclear antibody (ANA) Pattern (ICAP) was held on 22 September 2015, one day prior to the opening of the 12th Dresden Symposium on Autoantibodies in Dresden, Germany. The ultimate goal of ICAP is to promote harmonization and understanding of autoantibody nomenclature, and thereby optimizing ANA usage in patient care. The newly developed ICAP website www.ANApatterns.org was introduced to the more than 50 participants. This was followed by several presentations and discussions focusing on key issues including the two-tier classification of ANA patterns into competent-level versus expert-level, the consideration of how to report composite versus mixed ANA patterns, and the necessity for developing a consensus on how ANA results should be reported. The need to establish on-line training modules to help users gain competency in identifying ANA patterns was discussed as a future addition to the website. To advance the ICAP goal of promoting wider international participation, it was agreed that there should be a consolidated plan to translate consensus documents into other languages by recruiting help from members of the respective communities. PMID- 27252256 TI - Toward new criteria for systemic lupus erythematosus-a standpoint. AB - While clearly different in their aims and means, classification and diagnosis both try to accurately label the disease patients are suffering from. For systemic lupus erythematosus (SLE), this is complicated by the multi-organ nature of the disease and by our incomplete understanding of its pathophysiology. Hallmarks of SLE are the presence of antinuclear antibodies (ANA), and multiple immune-mediated organ symptoms that are largely independent. In an attempt to overcome limitations of the current sets of SLE classification criteria, a new four-phase approach is being developed, which is jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). This review attempts to delineate the performance of the current sets of criteria, the reasons for the decision for classification, and not diagnostic, criteria, and to provide a background of the current approach taken. PMID- 27252258 TI - Autoantibodies, complement and type I interferon as biomarkers for personalized medicine in SLE. AB - Systemic lupus erythematosus (SLE) can be a mysterious disease, presenting with extremely divergent clinical phenotypes. Already, biomarkers are very helpful tools for diagnosis, assessment and monitoring of disease activity, differential diagnosis of clinical manifestations, prediction of the disease course and stratified therapy, and they hold the key to personalized medicine in SLE. We summarize the clinical information that can only be supplied by autoantibodies, complement components and interferon biomarkers in this diverse disease. PMID- 27252257 TI - Multiparametric detection of autoantibodies in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a heterogeneous disease with respect to disease manifestations, disease progression and treatment response. Therefore, strategies to identify biomarkers that help distinguishing SLE subgroups are a major focus of biomarker research. We reasoned that a multiparametric autoantibody profiling approach combined with data mining tools could be applied to identify SLE patient clusters. We used a bead-based array containing 86 antigens including diverse nuclear and immune defense pathway proteins. Sixty four autoantibodies were significantly (p < 0.05) increased in SLE (n = 69) compared to healthy controls (HC, n = 59). Using binary cut-off thresholds (95% quantile of HC), hierarchical clustering of SLE patients yields five clusters, which differ qualitatively and in their total number of autoantibodies. In two patient clusters the overall accumulated autoantibody reactivity of all antigens tested was 31% and 48%, respectively. We observed a positive association between the autoantibody signature present in these two patient clusters and the clinical manifestation of glomerulonephritis (GLMN). In addition, groups of autoantibodies directed against distinct intracellular compartments and/or biological motifs characterize the different SLE subgroups. Our findings highlight the relevant potential of multiparametric autoantibody detection and may contribute to a deeper understanding of the clinical and serological diversity of SLE. PMID- 27252259 TI - Advances in the treatment of cutaneous lupus erythematosus. AB - Lupus erythematosus (LE) is a multifactorial autoimmune disease with clinical manifestations of differing severity which may present with skin manifestations as primary sign of the disease (cutaneous lupus erythematosus, CLE) or as part of a disease spectrum (systemic lupus erythematosus, SLE). To date, no drugs are approved specifically for the treatment of CLE and only single agents have been applied in randomized controlled trials. Therefore, topical and systemic agents are used "off-label", primarily based on open-label studies, case series, retrospective analyses, and expert opinions. In contrast, several agents, such as hydroxychloroquine, chloroquine, cyclophosphamide, azathioprine, and belimumab, are approved for the treatment of SLE. Recent approaches in the understanding of the molecular pathogenesis of LE enabled the development of further new agents, which target molecules such as interleukin 6 (IL-6) and interferon (IFN). Only single trials, however, applied these new agents in patients with cutaneous involvement of the disease and/or included endpoints which evaluated the efficacy of these agents on skin manifestations. This article provides an updated review on new and recent approaches in the treatment of CLE. PMID- 27252260 TI - Preventing the development of SLE: identifying risk factors and proposing pathways for clinical care. AB - Although challenging, developing evidence-based approaches to an early and accurate diagnosis of systemic lupus erythematosus is a key approach to preventing disease and lupus-associated morbidity and mortality. Advances in our understanding of preclinical and incomplete lupus erythematosus have enabled the identification of risk factors that may predict disease and the development of potential strategies aimed at primary prevention. Emerging data support the notion that there is a temporal disease progression from initial asymptomatic autoimmunity (preclinical lupus) through early clinical features of the disease (incomplete lupus erythematosus) to finally becoming fully classifiable systemic lupus erythematosus (complete lupus erythematosus). Here, we review the demographic, clinical, biomarker as well as genetic and environmental features that are reported to increase the risk of disease progression. Based on these risk factors, we propose a clinical care pathway for patients with early disease. We envisage that such a pathway, through early identification of disease, may improve patient outcomes, while reducing health care costs. PMID- 27252261 TI - B-cell subsets, signaling and their roles in secretion of autoantibodies. AB - B cells play a pivotal role in the pathogenesis of autoimmune diseases. In patients with systemic lupus erythematosus (SLE), the percentages of plasmablasts and IgD(-)CD27(-) double-negative memory B cells in peripheral blood are significantly increased, while IgD(+)CD27(+) IgM memory B cells are significantly decreased compared to healthy donors. The phenotypic change is significantly associated with disease activity and concentration of autoantibodies. Treatment of B-cell depletion using rituximab results in the reconstitution of peripheral B cells in SLE patients with subsequent improvement in disease activity. Numerous studies have described abnormalities in B-cell receptor (BCR)-mediated signaling in B cells of SLE patients. Since differences in BCR signaling are considered to dictate the survival or death of naive and memory B cells, aberrant BCR signal can lead to abnormality of B-cell subsets in SLE patients. Although Syk and Btk function as key molecules in BCR signaling, their pathological role in SLE remains unclear. We found that Syk and Btk do not only transduce activation signal through BCR, but also mediate crosstalk between BCR and Toll-like receptor (TLR) as well as BCR and JAK-STAT pathways in human B cells in vitro. In addition, pronounced Syk and Btk phosphorylation was observed in B cells of patients with active SLE compared to those of healthy individuals. The results suggest the involvement of Syk and Btk activation in abnormalities of BCR mediated signaling and B-cell phenotypes during the pathological process of SLE and that Syk, Btk and JAK are potential therapeutic targets in SLE. PMID- 27252262 TI - Organ involvement other than lupus nephritis in childhood-onset systemic lupus erythematosus. AB - In this review we critically analyze pulmonary, gastrointestinal and cardiac manifestations of childhood-onset systemic lupus erythematosus (cSLE). Clinical manifestations of these organ systems may be the initial manifestation of cSLE; frequently occur with very active cSLE; and are potential life-threatening manifestations often presenting to the emergency department and requiring admission to the intensive care unit. Early recognition and treatment of the pulmonary, gastrointestinal and cardiac manifestations of cSLE will result in improved prognosis and better outcomes. PMID- 27252263 TI - International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies. AB - OBJECTIVE: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). PATIENTS AND METHODS: A total of 1431 samples (SLE, n = 843; disease controls, n = 588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n = 566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off of > 4 was used to define active disease. RESULTS: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (p < 0.0001) in active SLE (SLEDAI-2K > 4; n = 232; median value 83.0 IU/mL) versus the inactive patients (n = 573; median value 22.3 IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearman's rho = 0.44, p < 0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. CONCLUSIONS: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity. PMID- 27252264 TI - Anti-C1q in systemic lupus erythematosus. AB - C1q is the first component of the classical complement pathway. Both clinically validated in-house ELISA assays as well as commercial ELISA kits are used for detection of anti-C1q antibodies. Anti-C1q autoantibodies can be detected in a wide range of autoimmune diseases and are highly sensitive for hypocomplementemic uticarial vasculitis. In SLE, anti-C1q are strongly associated with proliferative lupus nephritis, and their absence carries a negative predictive value for development of lupus nephritis of close to 100%. Anti-C1q in combination with anti-dsDNA and low complement has the strongest serological association with renal involvement. The anti-C1q titers correlate with global disease activity scores in patients with renal involvement, and higher titers seem to precede renal flares. After the successful treatment of a renal flare, anti-C1q has the tendency to decrease or even become undetectable. The main obstacle to the inclusion of anti-C1q in the classification criteria and clinical management of SLE is the lack of standardized laboratory assays. PMID- 27252265 TI - Complement levels and anti-C1q autoantibodies in patients with neuropsychiatric systemic lupus erythematosus. AB - OBJECTIVE: The objective of this paper is to analyse serum levels of anti-C1q, C1q circulating immune complexes (CIC), complement activation and complement components in systemic lupus erythematosus (SLE) patients during the first central nervous system neuropsychiatric (NP) event and to define the possible association between these results and clinical and laboratory characteristics. METHODS: A total of 280 patients suspected of having NP involvement due to SLE were recruited in the Leiden NPSLE-clinic. All SLE patients were classified according to the ACR 1982 revised criteria for the classification of SLE. The clinical disease activity was measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and NP diagnoses were classified according to the 1999 ACR case definitions for NPSLE. We measured in serum of all patients anti-C1q and C1q CIC levels, the activation capacity of complement (CH50 and AP50) and different complement components (C1q, C3, C4). RESULTS: In 92 patients the symptoms were attributed to SLE. NPSLE patients consisted of 63 patients with focal NPSLE and 34 patients with diffuse NPSLE. Anti-C1q antibodies were significantly higher and CH50, AP50 and C3 were significantly lower in NPSLE patients compared with SLE patients without NPSLE. This association was specially marked for diffuse NPSLE while no differences were found for focal NPSLE. After using potential predictors, decreased C4 remained significantly associated with focal NPSLE, but only when antiphospholipid antibodies (aPL) were included in the model. C3 and AP50 were independently associated with diffuse NPSLE. When SLEDAI-2K was included in the model these two associations were lost. When individual NPSLE syndromes were analysed, psychosis and cognitive dysfunction showed significantly lower values of complement activation capacity and all complement components. No significant associations were seen for other individual NPSLE syndromes. CONCLUSION: The associations between diffuse NPSLE and anti-C1q, C3/AP50 and focal NPSLE and C4 may be explained by disease activity and the presence of aPL, respectively. The role of complement activation and complement components in lupus psychosis and cognitive dysfunction merits further research. PMID- 27252266 TI - Clinical and serological associations of autoantibodies to the Ku70/Ku80 heterodimer determined by a novel chemiluminescent immunoassay. AB - BACKGROUND: Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of anti-Ku antibodies in different medical conditions using a novel chemiluminescent immunoassay. PATIENTS AND METHODS: Serum samples from adult patients with systemic lupus erythematosus (SLE, n=305), systemic sclerosis (SSc, n=70) and autoimmune myositis patients (AIM, n=109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n=30; infectious diseases, n=17) and healthy individuals (n=167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n=1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLE patient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review. RESULTS AND FINDINGS: In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious disease patients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs. CONTROLS: In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA. CONCLUSION: Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc. PMID- 27252267 TI - Development and multi-center evaluation of a novel immunoadsorption method for anti-DFS70 antibodies. AB - OBJECTIVE: Antinuclear antibodies (ANA) represent a hallmark in the diagnosis of ANA-associated rheumatic diseases (AARD). However, anti-DFS70 antibodies are present in a higher portion of the healthy individuals (HI) than in patients with AARD. Consequently, we developed a novel, highly specific indirect immunofluorescence (IIF) method that blocks anti-DFS70 antibodies from binding to HEp-2 cells and to evaluate the method in a multi-center study. METHODS: A total of 18 samples from systemic lupus erythematosus patients (SLE, n = 7) and HI (n = 11) were used for the initial development of the immunoadsorption method. For the multi-center evaluation, samples with a dense fine speckled (DFS) pattern (n = 99) were collected at three different sites based on their established IIF screening procedure at the respective laboratories. Additionally, four characterized samples with established clinically relevant IIF patterns (centromere, nucleolar, speckled, homogeneous) were blended in five different ratios (10%, 25%, 50%, 75%, 90%) with a sample positive for anti-DFS70 antibodies, which by itself showed a dense fine speckled (DFS) IIF pattern. All samples were tested by IIF with NOVA Lite HEp-2 ANA and NOVA Lite HEp-2 Select on the NOVA View(r) instrument, and also tested by QUANTA Flash DFS70 chemiluminescent immunoassay (CIA) for confirmation of anti-DFS70 antibodies (Inova Diagnostics, San Diego, CA, USA). RESULTS: For the development of the immunoadsorption method, only 1/7 ANA-positive samples from SLE patients, but 8/10 ANA-positive samples from healthy individuals turned negative using the immunoadsorption. Subsequently, 73/99 (73.7%) of the DFS pattern samples were positive by CIA for anti-DFS70 antibodies showing a strong quantitative Spearman's correlation (rho = 0.57 (95% CI, 0.39-0.71, p < 0.0001)) between light intensity units (LIU) measured by NOVA View and CIA. Intensities measured with NOVA Lite HEp-2 and NOVA Lite HEp-2 Select demonstrated significantly lower intensity values after inhibition with DFS70 antigen (p < 0.0001). When samples were processed to mimic samples with mixed patterns (DFS + clinically relevant pattern), the new immunoadsorption method demonstrated that all clinically relevant patterns remained unchanged whereas the LIUs from NOVA View analysis significantly decreased after inhibition (p < 0.0001). CONCLUSION: The data showed that the NOVA Lite HEp-2 Select kit effectively inhibits anti-DFS70 antibody binding to its cellular target antigen. PMID- 27252268 TI - Anti-beta-2 glycoprotein I epitope specificity: from experimental models to diagnostic tools. AB - Beta-2 glycoprotein I (beta2GPI) is the main antigenic target for anti phospholipid antibodies (aPL), the serological markers of anti-phospholipid syndrome (APS). Conformational changes of the molecule seem to be essential for exposing the cryptic epitope for aPL binding and to trigger pathogenic pathways. There is increasing evidence that a conformational epitope located in the Domain I (DI) of the molecule is the main epitope targeted by human autoantibodies. The pathogenic role of the DI epitope has been recently supported by in vivo models and by immuno-histopathological findings in APS patients. Antibodies targeting beta2GPI-DI are more frequently detected in patients with full-blown APS compared to asymptomatic aPL carriers or patients with infectious diseases who have antibodies directed against the whole molecule. Anti-DI antibodies are positively correlated with medium to high titres of aPL, with the presence of lupus anticoagulant and thrombotic and pregnancy manifestations, enabling identification of patients at higher risk of clinical events. However, some APS patients develop antibodies reacting against beta2GPI epitopes other than DI, suggesting that other anti-beta2GPI antibody subsets may be clinically relevant. Although preliminary results suggest that anti-DI antibodies can be detected by different assays in a comparable manner, further prospective studies are needed to support their use in the clinical setting and their predictive value. PMID- 27252269 TI - Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome. AB - INTRODUCTION: Antibodies to the domain 1 of beta 2 glycoprotein I (beta2GPI-D1) have been suggested as a risk marker for thrombosis in patients with the antiphospholipid syndrome (APS). This cross-sectional study aimed to analyze the clinical utility of a novel chemiluminescence assay for the detection of anti beta2GPI-D1 antibodies. PATIENTS AND METHODS: Sera collected from patients with primary or secondary APS (n = 106; 72 with and 34 without history of thrombosis) and controls (n = 272) were tested for anti-beta2GPI-D1 IgG by chemiluminescence assay (QUANTA Flash) and by two anti-beta2GPI IgG assays (QUANTA Lite and QUANTA Flash beta2GPI IgG). RESULTS: Anti-beta2GPI-D1 IgG titers were significantly higher in patients with thrombosis (P = 0.0032) than those without. At the cut off of 20 units, which yielded a 99.5% specificity, 24 of 72 (34.9%) patients with thrombosis and four of 34 (11.8%) without thrombosis were anti-beta2GPI-D1 IgG positive (odds ratio, OR = 4.0). By further optimizing the cut-off specifically for correlation with thrombosis, 20.8% of the patients with thrombosis and 2.9% of the patients without thrombosis were positive (OR = 8.7). The ORs were significantly lower for antibodies to the full-length beta2GPI by either the chemiluminescence assay or ELISA. Using the anti-beta2GPI chemiluminescence assay, the OR was 2.3 (recommended cut-off of 20 CU) or 4.1 (optimal cut-off 164.6 CU). Using the anti-beta2GPI ELISA, the OR was 2.7 (recommended cut-off of 20 units) or 3.7 (optimal cut-off 7.6 units). CONCLUSION: These data indicate that anti-beta2GPI-D1 IgG are present more frequently and in higher titers in APS patients with thrombotic complications than in those without.The novel beta2GPI-D1 chemiluminescence assay appears to be superior to full-length beta2GPI assays for the risk assessment of thrombotic events in APS patients. PMID- 27252270 TI - Diagnostic ANCA algorithms in daily clinical practice: evidence, experience, and effectiveness. AB - Detection of antineutrophil cytoplasmic antibodies (ANCA) for ANCA-associated vasculitides (AAV) is based on indirect immunofluorescence (IIF) on ethanol-fixed neutrophils and reactivity toward myeloperoxidase (MPO) and proteinase 3 (PR3). According to the international consensus for ANCA testing, presence of ANCA should at least be screened for by IIF and, if positive, followed by antigen specific immunoassays. Optimally, all samples are analyzed by both IIF and quantitative antigen-specific immunoassays. Since the establishment of this consensus many new technologies have become available and this has challenged the positioning of IIF in the testing algorithm for AAV. In the current paper, we summarize the novelties in ANCA diagnostics and discuss the possible implications of these developments for the different ANCA algorithms that are currently applied in routine diagnostic laboratories. Possible consequences of replacing ANCA assays by novel methods are illustrated by our data obtained in daily clinical practice. Eventually, it is questioned if there is a need to change the consensus, and if so, whether IIF can be discarded completely, or be used as a confirmation assay instead of a screening assay. Both alternative options require that ANCA requests for AAV can be separated from ANCA requests for gastrointestinal autoimmune diseases. PMID- 27252271 TI - Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. AB - Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are closely associated with interstitial lung disease in polymyositis and dermatomyositis. Anti-ARS-positive patients develop common clinical characteristics termed anti-synthetase syndrome and share a common clinical course, in which they respond well to initial treatment with glucocorticoids but in which disease tends to recur when glucocorticoids are tapered. Anti-MDA5 antibody is associated with rapidly progressive interstitial lung disease and poor prognosis, particularly in Asia. Therefore, intensive immunosuppressive therapy is required for anti-MDA5-positive patients from the early phase of the disease. New enzyme-linked immunosorbent assays to detect anti ARS and anti-MDA5 antibodies have recently been established and are suggested to be efficient and useful. These assays are expected to be widely applied in daily practice. PMID- 27252272 TI - Sweet but dangerous - the role of immunoglobulin G glycosylation in autoimmunity and inflammation. AB - Glycosylation is well-known to modulate the functional capabilities of immunoglobulin G (IgG)-mediated cellular and humoral responses. Indeed, highly sialylated and desialylated IgG is endowed with anti- and pro-inflammatory activities, respectively, whereas fully deglycosylated IgG is a rather lame duck, with no effector function besides toxin neutralization. Recently, several studies revealed the impact of different glycosylation patterns on the Fc part and Fab fragment of IgG in several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we provide a synoptic update summarizing the most important aspects of antibody glycosylation, and the current progress in this field. We also discuss the therapeutic options generated by the modification of the glycosylation of IgG in a potential treatment for chronic inflammatory diseases. PMID- 27252273 TI - Reactive oxygen homeostasis - the balance for preventing autoimmunity. AB - Being mainly known for their role in the antimicrobial defense and collateral damage they cause in tissues as agents of oxidative stress, reactive oxygen species were considered "the bad guys" for decades. However, in the last years it was shown that the absence of reactive oxygen species can lead to the development of immune-mediated inflammatory diseases. Animal models of lupus, arthritis and psoriasis revealed reactive oxygen species-deficiency as a potent driver of pathogenesis. On the contrary, in chronic stages oxidative stress can still contribute to progression of inflammation. It seems that a neatly adjusted redox balance is necessary to sustain an immune state that both prevents the development of overt autoimmunity and attenuates chronic stages of disease. PMID- 27252274 TI - GPs charged with manslaughter of 12 year old boy are acquitted. PMID- 27252276 TI - Molecular picture of cobalamin C/D defects before and after newborn screening era. AB - Objective Birth prevalence of Cobalamin (Cbl) C or D defects in Portugal is an estimated 1:85,000, one of the highest worldwide. We compared the genotype/phenotype of patients identified with CblC or CblD before and after the implementation of expanded newborn screening. Methods Twenty-five Portuguese CblC/D patients, 14 symptomatic and 11 identified through screening, were diagnosed using gas chromatography or tandem mass spectrometry. Molecular characterization was performed through the study of MMACHC and MMADHC genes. Results The most common MMACHC mutation, c.271dupA, was present in 100% of MMACHC alleles of all CblC screened patients, in contrast with the 61% identified before expanded newborn screening. All studied cases (except one, who presented a CblD deficiency) presented a CblC defect. More CblC late-onset patients were diagnosed before the introduction of newborn screening than in the post newborn screening era, probably because some early onset patients died without a definitive diagnosis. Conclusion The molecular data found in this cohort contribute to the improvement of screening and diagnosis of Cbl defects and would enable a confirmatory diagnosis of these patients, reducing the need for complex, costly, laborious, and time-consuming biochemical/enzymatic tests. PMID- 27252277 TI - When Is It Appropriate to Use Arginine in Critical Illness? AB - In health, arginine is considered a nonessential amino acid but can become an essential amino acid (ie, conditionally essential amino acid) during periods of metabolic or traumatic stress as endogenous arginine supply is inadequate to meet physiologic demands. Arginine depletion in critical illness is associated with impairments in microcirculatory blood flow, impaired wound healing, and T-cell dysfunction. The purpose of this review is to (1) describe arginine metabolism and role in health and critical illness, (2) describe the relationship between arginine and asymmetric dimethylarginine, and (3) review studies of supplemental arginine in critically ill patients. PMID- 27252278 TI - Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics. AB - Across the Western World there is an increasing trend to postpone childbearing. Consequently, the negative influence of age on oocyte quality may lead to a difficulty in conceiving for many couples. Furthermore, lifestyle factors may exacerbate a couple's difficulty in conceiving due mainly to the metabolic influence of obesity; however, the negative impacts of low peripheral body fat, excessive exercise, the increasing prevalence of sexually transmitted diseases, and smoking all have significant negative effects on fertility. Other factors that impede conception are the perceived increasing prevalence of the polycystic ovary syndrome, which is further exacerbated by obesity, and the presence of uterine fibroids and endometriosis (a progressive pelvic inflammatory disorder) which are more prevalent in older women. A tendency for an earlier sexual debut and to have more sexual partners has led to an increase in sexually transmitted diseases. In addition, there are several genetic influences that may limit the number of oocytes within the ovary; consequently, by postponing attempts at childbearing, a limitation of oocyte number may become evident, whereas in previous generations with earlier conception this potentially reduced reproductive life span did not manifest in infertility. Environmental influences on reproduction are under increasing scrutiny. Although firm evidence is lacking however, dioxin exposure may be linked to endometriosis, phthalate exposure may influence ovarian reserve, and bisphenol A may interfere with oocyte development and maturation. However, chemotherapy or radiotherapy is recognized to lead to ovarian damage and predispose the woman to ovarian failure. PMID- 27252279 TI - TRPV4: Molecular Conductor of a Diverse Orchestra. AB - Transient receptor potential vanilloid type 4 (TRPV4) is a calcium-permeable nonselective cation channel, originally described in 2000 by research teams led by Schultz (Nat Cell Biol 2: 695-702, 2000) and Liedtke (Cell 103: 525-535, 2000). TRPV4 is now recognized as being a polymodal ionotropic receptor that is activated by a disparate array of stimuli, ranging from hypotonicity to heat and acidic pH. Importantly, this ion channel is constitutively expressed and capable of spontaneous activity in the absence of agonist stimulation, which suggests that it serves important physiological functions, as does its widespread dissemination throughout the body and its capacity to interact with other proteins. Not surprisingly, therefore, it has emerged more recently that TRPV4 fulfills a great number of important physiological roles and that various disease states are attributable to the absence, or abnormal functioning, of this ion channel. Here, we review the known characteristics of this ion channel's structure, localization and function, including its activators, and examine its functional importance in health and disease. PMID- 27252280 TI - Public Space, Public Waste, and the Right to the City. AB - I draw on my experiences as an organizer with a waste-pickers collective, Kagad Kach Patra Kashtakari Panchayat in Pune, India, to reflect on the power dynamics in control of public space. The Pune Municipal Corporation (PMC), a public body, has used public resources to facilitate and enable accumulation by private companies, who have not been able to produce what they had committed to in the processing of waste. The waste pickers, in alliance with affected village-based land agitation committees, have mobilized against the dumping that is ruining their way of life, environments, and health, and are fighting for their own integration into waste value chains. The article uses the frame of David Harvey's(1) "right to the city"; a key part of the mobilizing work with waste pickers has been Freirean conscientization methods to spread awareness of the economic importance, to the city and to the planet, of waste recycling. PMID- 27252281 TI - The Informal Economy: Recent Trends, Future Directions. AB - Informal employment represents more than half of nonagricultural employment in most developing regions, contributes to the overall economy, and provides pathways to reduction of poverty and inequality. Support to the informal economy should include the expansion of occupational health and safety to include informal workers, based on an analysis of their work places and work risks. The paper presents main schools of thought and argues for a holistic understanding of the different segments of the informal work force and for policies and interventions tailored to the needs and constraints of these different segments. The paper recommends a policy approach which seeks to extend social protection, including occupational health and safety services, to informal workers, and to increase the productivity of informal enterprises and informal workers through an enabling environment and support services. The paper calls for a new paradigm of a hybrid economy which would value and integrate the informal economy alongside the formal economies. PMID- 27252282 TI - Erratum. PMID- 27252291 TI - Last Exit to Differentiation: Histone Variants as Signposts. PMID- 27252293 TI - What the Nucellus Can Tell Us. PMID- 27252294 TI - Bringing Climate Change into the Life Science Classroom: Essentials, Impacts on Life, and Addressing Misconceptions. PMID- 27252292 TI - Phytochrome Signaling Is Mediated by PHYTOCHROME INTERACTING FACTOR in the Liverwort Marchantia polymorpha. AB - Phytochromes are red light (R) and far-red light (FR) receptors that play important roles in many aspects of plant growth and development. Phytochromes mainly function in the nucleus and regulate sets of genes by inhibiting negatively acting basic helix-loop-helix transcription factors named PHYTOCHROME INTERACTING FACTORs (PIFs) in Arabidopsis thaliana Although R/FR photoreversible responses and phytochrome genes are well documented in diverse lineages of plants, the extent to which phytochrome signaling is mediated by gene regulation beyond angiosperms remains largely unclear. Here, we show that the liverwort Marchantia polymorpha, an emerging model basal land plant, has only one phytochrome gene, Mp-PHY, and only one PIF gene, Mp-PIF These genes mediate typical low fluence responses, which are reversibly elicited by R and FR, and regulate gene expression. Mp-phy is light-stable and translocates into the nucleus upon irradiation with either R or FR, demonstrating that the single phytochrome Mp-phy exhibits combined biochemical and cell-biological characteristics of type I and type II phytochromes. Mp-phy photoreversibly regulates gemma germination and downstream gene expression by interacting with Mp PIF and targeting it for degradation in an R-dependent manner. Our findings suggest that the molecular mechanisms for light-dependent transcriptional regulation mediated by PIF transcription factors were established early in land plant evolution. PMID- 27252295 TI - Exploring the MACH Model's Potential as a Metacognitive Tool to Help Undergraduate Students Monitor Their Explanations of Biological Mechanisms. AB - When undergraduate biology students learn to explain biological mechanisms, they face many challenges and may overestimate their understanding of living systems. Previously, we developed the MACH model of four components used by expert biologists to explain mechanisms: Methods, Analogies, Context, and How. This study explores the implementation of the model in an undergraduate biology classroom as an educational tool to address some of the known challenges. To find out how well students' written explanations represent components of the MACH model before and after they were taught about it and why students think the MACH model was useful, we conducted an exploratory multiple case study with four interview participants. We characterize how two students explained biological mechanisms before and after a teaching intervention that used the MACH components. Inductive analysis of written explanations and interviews showed that MACH acted as an effective metacognitive tool for all four students by helping them to monitor their understanding, communicate explanations, and identify explanatory gaps. Further research, though, is needed to more fully substantiate the general usefulness of MACH for promoting students' metacognition about their understanding of biological mechanisms. PMID- 27252296 TI - Early Engagement in Course-Based Research Increases Graduation Rates and Completion of Science, Engineering, and Mathematics Degrees. AB - National efforts to transform undergraduate biology education call for research experiences to be an integral component of learning for all students. Course based undergraduate research experiences, or CUREs, have been championed for engaging students in research at a scale that is not possible through apprenticeships in faculty research laboratories. Yet there are few if any studies that examine the long-term effects of participating in CUREs on desired student outcomes, such as graduating from college and completing a science, technology, engineering, and mathematics (STEM) major. One CURE program, the Freshman Research Initiative (FRI), has engaged thousands of first-year undergraduates over the past decade. Using propensity score-matching to control for student-level differences, we tested the effect of participating in FRI on students' probability of graduating with a STEM degree, probability of graduating within 6 yr, and grade point average (GPA) at graduation. Students who completed all three semesters of FRI were significantly more likely than their non-FRI peers to earn a STEM degree and graduate within 6 yr. FRI had no significant effect on students' GPAs at graduation. The effects were similar for diverse students. These results provide the most robust and best-controlled evidence to date to support calls for early involvement of undergraduates in research. PMID- 27252297 TI - Multilevel Assessment of Middle School Students' Interest in the Health Sciences: Development and Validation of a New Measurement Tool. AB - Using the context of a 2-wk instructional unit focused on eye and vision health, we developed and validated a multilevel measure of middle school students' interest in science and health careers. This survey contained three subscales positioned differently with respect to curricular content. Interest in Vision Care was most related, but less transferrable to other contexts. Interest in Science was most general, and Interest in Healthcare was positioned between the two. We found that, with two exceptions, items fitted well with validity expectations and were stable across a 2-wk intervention. Further, measures of interest in science, health, and vision-care careers were shown to be reliable and valid. We found that ease of facilitating change across the intervention was generally greater in subscales closely related to the curricular context but that the average magnitude of change in Interest in Healthcare and Interest in Science was not significantly different. We discuss use of these measures in informing instructional efforts and advise that changes in students' perceptions of how science and healthcare relate should be considered in longitudinal analyses. PMID- 27252298 TI - Improved Student Learning through a Faculty Learning Community: How Faculty Collaboration Transformed a Large-Enrollment Course from Lecture to Student Centered. AB - Undergraduate introductory biology courses are changing based on our growing understanding of how students learn and rapid scientific advancement in the biological sciences. At Iowa State University, faculty instructors are transforming a second-semester large-enrollment introductory biology course to include active learning within the lecture setting. To support this change, we set up a faculty learning community (FLC) in which instructors develop new pedagogies, adapt active-learning strategies to large courses, discuss challenges and progress, critique and revise classroom interventions, and share materials. We present data on how the collaborative work of the FLC led to increased implementation of active-learning strategies and a concurrent improvement in student learning. Interestingly, student learning gains correlate with the percentage of classroom time spent in active-learning modes. Furthermore, student attitudes toward learning biology are weakly positively correlated with these learning gains. At our institution, the FLC framework serves as an agent of iterative emergent change, resulting in the creation of a more student-centered course that better supports learning. PMID- 27252299 TI - Cognitive Difficulty and Format of Exams Predicts Gender and Socioeconomic Gaps in Exam Performance of Students in Introductory Biology Courses. AB - Recent reform efforts in undergraduate biology have recommended transforming course exams to test at more cognitively challenging levels, which may mean including more cognitively challenging and more constructed-response questions on assessments. However, changing the characteristics of exams could result in bias against historically underserved groups. In this study, we examined whether and to what extent the characteristics of instructor-generated tests impact the exam performance of male and female and middle/high- and low-socioeconomic status (SES) students enrolled in introductory biology courses. We collected exam scores for 4810 students from 87 unique exams taken across 3 yr of the introductory biology series at a large research university. We determined the median Bloom's level and the percentage of constructed-response questions for each exam. Despite controlling for prior academic ability in our models, we found that males and middle/high-SES students were disproportionately favored as the Bloom's level of exams increased. Additionally, middle/high-SES students were favored as the proportion of constructed-response questions on exams increased. Given that we controlled for prior academic ability, our findings do not likely reflect differences in academic ability level. We discuss possible explanations for our findings and how they might impact how we assess our students. PMID- 27252300 TI - Development of a Lac Operon Concept Inventory (LOCI). AB - Concept inventories (CIs) are valuable tools for educators that assess student achievement and identify misconceptions held by students. Results of student responses can be used to adjust or develop new instructional methods for a given topic. The regulation of gene expression in both prokaryotes and eukaryotes is an important concept in genetics and one that is particularly challenging for undergraduate students. As part of a larger study examining instructional methods related to gene regulation, the authors developed a 12-item CI assessing student knowledge of the lac operon. Using an established protocol, the authors wrote open-ended questions and conducted in-class testing with undergraduate microbiology and genetics students to discover common errors made by students about the lac operon and to determine aspects of item validity. Using these results, we constructed a 12-item multiple-choice lac operon CI called the Lac Operon Concept Inventory (LOCI), The LOCI was reviewed by two experts in the field for content validity. The LOCI underwent item analysis and was assessed for reliability with a sample of undergraduate genetics students (n = 115). The data obtained were found to be valid and reliable (coefficient alpha = 0.994) with adequate discriminatory power and item difficulty. PMID- 27252301 TI - Opening Doors to Inclusion and Engagement. PMID- 27252302 TI - President's Message: Transcultural Nursing Certification: Credentials Matter. PMID- 27252303 TI - The Migrant Crisis and Social Justice. PMID- 27252305 TI - Mutational Evidence for the Critical Role of CBF Transcription Factors in Cold Acclimation in Arabidopsis. AB - The three tandemly arranged CBF genes, CBF1, CBF2, and CBF3, are involved in cold acclimation. Due to the lack of stable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants deficient in all three CBF genes, it is still unclear whether the CBF genes are essential for freezing tolerance and whether they may have other functions besides cold acclimation. In this study, we used the CRISPR/Cas9 system to generate cbf single, double, and triple mutants. Compared to the wild type, the cbf triple mutants are extremely sensitive to freezing after cold acclimation, demonstrating that the three CBF genes are essential for cold acclimation. Our results show that the three CBF genes also contribute to basal freezing tolerance. Unexpectedly, we found that the cbf triple mutants are defective in seedling development and salt stress tolerance. Transcript profiling revealed that the CBF genes regulate 414 cold-responsive (COR) genes, of which 346 are CBF-activated genes and 68 are CBF-repressed genes. The analysis suggested that CBF proteins are extensively involved in the regulation of carbohydrate and lipid metabolism, cell wall modification, and gene transcription. Interestingly, like the triple mutants, cbf2 cbf3 double mutants are more sensitive to freezing after cold acclimation compared to the wild type, but cbf1 cbf3 double mutants are more resistant, suggesting that CBF2 is more important than CBF1 and CBF3 in cold acclimation-dependent freezing tolerance. Our results not only demonstrate that the three CBF genes together are required for cold acclimation and freezing tolerance, but also reveal that they are important for salt tolerance and seedling development. PMID- 27252307 TI - Using Random Forest Models to Identify Correlates of a Diabetic Peripheral Neuropathy Diagnosis from Electronic Health Record Data. AB - Objective: To identify variables correlated with a diagnosis of diabetic peripheral neuropathy (DPN) using random forest modeling applied to electronic health records. Design: Retrospective analysis. Setting: Humedica de-identified electronic health records database. Subjects: Subjects >= 18 years old with type 2 diabetes from January 1, 2008-September 30, 2013 having continuous data for 1 year pre- and postindex with DPN (n = 35,050) and without DPN (n = 288,328) were identified. Methods: Demographic, clinical, and health care resource utilization variables (e.g., inpatient and outpatient encounters, medications, and procedures) were input into a random forest model to identify the most important correlates of a DPN diagnosis. Random forest modeling is a computationally extensive, robust data mining technique that accommodates large sets of variables to identify associated factors using an ensemble of classifications trees. Accuracy of the model was evaluated using receiver operating characteristic curves (ROC). Results: The final random forest model consisted of the following variables (importance) associated with a DPN diagnosis: Charlson Comorbidity Index score (100%), age (37.1%), number of pre-index procedures and services (29.7%), number of pre-index outpatient prescriptions (24.2%), number of pre index outpatient visits (18.3%), number of pre-index laboratory visits (16.9%), number of pre-index outpatient office visits (12.1%), number of inpatient prescriptions (5.9%), and number of pain-related medication prescriptions (4.4%). ROC analysis confirmed model performance, with an area under the curve of 0.824 and accuracy of 89.6% (95% confidence interval 89.4%, 89.8%). Conclusions: Random forest modeling can determine likelihood of a DPN diagnosis. Further validation of the random forest model may help facilitate earlier diagnosis and enhance management strategies. PMID- 27252306 TI - Chloroplast-Specific in Vivo Ca2+ Imaging Using Yellow Cameleon Fluorescent Protein Sensors Reveals Organelle-Autonomous Ca2+ Signatures in the Stroma. AB - In eukaryotes, subcellular compartments such as mitochondria, the endoplasmic reticulum, lysosomes, and vacuoles have the capacity for Ca(2+) transport across their membranes to modulate the activity of compartmentalized enzymes or to convey specific cellular signaling events. In plants, it has been suggested that chloroplasts also display Ca(2+) regulation. So far, monitoring of stromal Ca(2+) dynamics in vivo has exclusively relied on using the luminescent Ca(2+) probe aequorin. However, this technique is limited in resolution and can only provide a readout averaged over chloroplast populations from different cells and tissues. Here, we present a toolkit of Arabidopsis (Arabidopsis thaliana) Ca(2+) sensor lines expressing plastid-targeted FRET-based Yellow Cameleon (YC) sensors. We demonstrate that the probes reliably report in vivo Ca(2+) dynamics in the stroma of root plastids in response to extracellular ATP and of leaf mesophyll and guard cell chloroplasts during light-to-low-intensity blue light illumination transition. Applying YC sensing of stromal Ca(2+) dynamics to single chloroplasts, we confirm findings of gradual, sustained stromal Ca(2+) increases at the tissue level after light-to-low-intensity blue light illumination transitions, but monitor transient Ca(2+) spiking as a distinct and previously unknown component of stromal Ca(2+) signatures. Spiking was dependent on the availability of cytosolic Ca(2+) but not synchronized between the chloroplasts of a cell. In contrast, the gradual sustained Ca(2+) increase occurred independent of cytosolic Ca(2+), suggesting intraorganellar Ca(2+) release. We demonstrate the capacity of the YC sensor toolkit to identify novel, fundamental facets of chloroplast Ca(2+) dynamics and to refine the understanding of plastidial Ca(2+) regulation. PMID- 27252308 TI - Association Between Carbohydrate Nutrition and Successful Aging Over 10 Years. AB - BACKGROUND: We prospectively examined the relationship between dietary glycemic index (GI) and glycemic load (GL), carbohydrate, sugars, and fiber intake (including fruits, vegetable of breads/cereals fiber) with successful aging (determined through a multidomain approach). METHODS: A total of 1,609 adults aged 49 years and older who were free of cancer, coronary artery disease, and stroke at baseline were followed for 10 years. Dietary data were collected using a semiquantitative Food Frequency Questionnaire. Successful aging status was determined through interviewer-administered questionnaire at each visit and was defined as the absence of disability, depressive symptoms, cognitive impairment, respiratory symptoms, and chronic diseases (eg, cancer and coronary artery disease). RESULTS: In all, 249 (15.5%) participants had aged successfully 10 years later. Dietary GI, GL, and carbohydrate intake were not significantly associated with successful aging. However, participants in the highest versus lowest (reference group) quartile of total fiber intake had greater odds of aging successfully than suboptimal aging, multivariable-adjusted odds ratio (OR), 1.79 (95% confidence interval [CI] 1.13-2.84). Those who remained consistently below the median in consumption of fiber from breads/cereal and fruit compared with the rest of cohort were less likely to age successfully, OR 0.53 (95% CI 0.34-0.84) and OR 0.64 (95% CI 0.44-0.95), respectively. CONCLUSIONS: Consumption of dietary fiber from breads/cereals and fruits independently influenced the likelihood of aging successfully over 10 years. These findings suggest that increasing intake of fiber-rich foods could be a successful strategy in reaching old age disease free and fully functional. PMID- 27252309 TI - Sexual Function and Mortality in Older Men: The Concord Health and Ageing in Men Project. AB - Background : The longitudinal association between progressive temporal change in sexual (dys)function and mortality in older men. Methods : Community-dwelling men aged 70 years and older from the Concord Health and Ageing in Men Project were assessed at baseline (2005-2007, n = 1,705), 2-years follow-up (n = 1,367), and 5 years follow-up (n = 958). Self-reported sexual function (erectile function and sexual activity) using standardized questions were analyzed by generalized estimating equations to examine the longitudinal prediction of mortality according to change in sexual function across three time-points. Results : Men reported to have erectile dysfunction increased from 64% to 80%, and to be sexually inactive increased from 56% to 59% over the course follow-up. In univariate analyses, erectile dysfunction (hazard ratio: 2.02, 95% confidence interval [CI]: 1.45-2.81) or having no sexual activity (hazard ratio: 2.31, 95% CI: 1.82-2.93) at baseline predicted increased mortality over the subsequent 7 years. Models adjusted for multivariate and major reproductive hormones had negligible impact on mortality prediction, but neither statistically significantly predicted mortality after adjusting for depression. Similarly, change in erectile dysfunction over time was associated with mortality over 7 years in univariate (odds ratio: 1.69, 95% CI: 1.34-2.14) and multivariate analysis, including hormones, but not after adjusting for depression (odds ratio: 1.24, 95% CI: 0.95-1.62). Change in sexual activity was associated with mortality over 7 years in univariate analysis (odds ratio: 2.37, 95% CI: 1.33-4.20) but not after adjusting for age (odds ratio: 1.45, 95% CI: 0.79-2.64). Conclusions : Our analyses suggest sexual dysfunction was not an independent risk factor of, but rather may be a biomarker for, all-cause mortality in older men. PMID- 27252310 TI - A tennis lesson: sharp practice in the science behind the Sharapova case. PMID- 27252311 TI - Improving multidisciplinary severe sepsis management using the Sepsis Six. PMID- 27252312 TI - A reflection on our day-to-day clinical practice: can we increase the predictability of pulmonary embolism (PE) by combining D-dimer with other biochemical variables and CXR findings? PMID- 27252313 TI - The role of palliative medicine in the acute medical admitting unit. PMID- 27252314 TI - When routine 7-day ambulatory ECG monitoring should be advocated in patients with ischaemic stroke. PMID- 27252315 TI - More discussions needed about resuscitation? DNAR orders in a district general hospital. PMID- 27252316 TI - Improving the documentation of pleural procedures: the impact of a new standardised pleural procedure pro forma. PMID- 27252317 TI - Good results of chronic HCV management in a single centre prison population. PMID- 27252318 TI - Which palliative care patients are most likely to benefit from parenteral nutrition? A retrospective service evaluation. PMID- 27252319 TI - Occlusion of uncommon anatomic variant of thalamic blood supply (so-called artery of Percheron) presenting as bilateral thalamic infarcts. PMID- 27252320 TI - Standardising the management of alcohol withdrawal at an NHS district general hospital. PMID- 27252321 TI - Advanced care planning in the elderly, are we doing it? PMID- 27252322 TI - Lumbar puncture: low-cost interventions improve efficiency and patient experience. PMID- 27252323 TI - Assessment of excision of basal cell carcinoma: did GPs really 'underperform'? PMID- 27252324 TI - Adequacy of fluid balance chart documentation on wards. PMID- 27252325 TI - A retrospective study of quality of care of patients with decompensated liver cirrhosis in the first 24 hours of admission to a local district general hospital in the UK. PMID- 27252326 TI - Paraneoplastic myositis: case report and review of literature. PMID- 27252327 TI - A rare case of Erdheim-Chester disease. PMID- 27252328 TI - An audit to establish the role of the gastroenterologist in patients who are diagnosed with acute severe colitis and go onto have a colectomy at Great Western Hospitals NHS Foundation Trust (GWH). PMID- 27252329 TI - Use of information technology and education improved screening for cognitive impairment in the over 65s. PMID- 27252330 TI - A case of posterior reversible encephalopathy syndrome. PMID- 27252331 TI - Faecal calprotectin - the Crohn's disease activity predictor of the future. PMID- 27252332 TI - The study of cytoskeletal regulators on cell motility using Dictyostelium discoideum as a model organism with a view to human application in Marfan's syndrome and valvular diseases. PMID- 27252333 TI - Acute hospital at home: a new age. PMID- 27252334 TI - Definition and delivery of an aortopathy bundle of care (ABC): a tool for improving diagnosis and management of Marfan syndrome and related conditions. PMID- 27252335 TI - Evaluation of the Aintree Stroke Alert System (SAS) - an elite multidisciplinary 'brain attack' team. PMID- 27252336 TI - How long do patients with chronic disease expect to live? A systematic review of the literature. PMID- 27252337 TI - A community integrated respiratory team can improve patient care, quality of life and reduce hospital stays. PMID- 27252338 TI - Efficacy and relapse rates of different Isotretinoin dosages in treating acne vulgaris: systemic review. PMID- 27252339 TI - A critical appraisal on whether a traumatic pneumothorax should be managed conservatively. PMID- 27252340 TI - Side rooms on the medical assessment unit - safety versus privacy and dignity. PMID- 27252341 TI - Improving 7-day working: face-to-face handover. PMID- 27252342 TI - Clinical manifestations of prune belly syndrome. PMID- 27252343 TI - Type-1 diabetes revisited and lessons learned. PMID- 27252344 TI - Use of the age-adjusted D-dimer as a screening tool for pulmonary thromboembolic disease in an older inpatient population. PMID- 27252345 TI - Do patients with neutropenic sepsis need granulocyte stimulating factor (GCSF)? PMID- 27252346 TI - Cause of long-term mortality among diabetics undergoing percutaneous coronary intervention. PMID- 27252347 TI - Association between bibliometric parameters, reporting and methodological quality of randomised controlled trials in vascular and endovascular surgery. AB - Purpose We aimed to investigate association between bibliometric parameters, reporting and methodological quality of vascular and endovascular surgery randomised controlled trials. Methods The most recent 75 and oldest 75 randomised controlled trials published in leading journals over a 10-year period were identified. The reporting quality was analysed using the CONSORT statement, and methodological quality with the Intercollegiate Guidelines Network checklist. We used exploratory univariate and multivariable linear regression analysis to investigate associations. Findings Bibliometric parameters such as type of journal, study design reported in title, number of pages; external funding, industry sponsoring and number of citations are associated with reporting quality. Moreover, parameters such as type of journal, subject area and study design reported in title are associated with methodological quality. Conclusions The bibliometric parameters of randomised controlled trials may be independent predictors for their reporting and methodological quality. Moreover, the reporting quality of randomised controlled trials is associated with their methodological quality and vice versa. PMID- 27252348 TI - Region- and Layer-Specific Activation of the Higher Order Auditory Cortex Te2 after Remote Retrieval of Fear or Appetitive Memories. AB - The auditory cortex is involved in encoding sounds which have acquired an emotional-motivational charge. However, the neural circuitry engaged by emotional memory processes in the auditory cortex is poorly understood. In this study, we investigated the layers and regions that are recruited in the higher order auditory cortex Te2 by a tone previously paired to either fear or appetitive stimuli in rats. By tracking the protein coded by the immediate early gene zif268, we found that fear memory retrieval engages layers II-III in most regions of Te2. These results were neither due to an enhanced fear state nor to fear evoked motor responses, as they were absent in animals retrieving an olfactory fear memory. These layers were also activated by appetitive auditory memory retrieval. Strikingly, layer IV was recruited by fear, but not appetitive memories, whereas layer V activity was related to the behavioral responses displayed to the CS. In addition to revealing the layers and regions that are recruited in the Te2 by either fear or appetitive remote memories, our study also shows that the neural circuitry within the Te2 that processes and stores emotional memories varies on the basis of the affective motivational charge of tones. PMID- 27252349 TI - Ultrasound Enhances the Expression of Brain-Derived Neurotrophic Factor in Astrocyte Through Activation of TrkB-Akt and Calcium-CaMK Signaling Pathways. AB - Low-intensity pulsed ultrasound (LIPUS) stimulation has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in astrocytes of an in vitro model and rat brains of an in vivo model; however, their molecular mechanisms are still not well clarified. Here, we investigated the underlying mechanisms of BDNF enhancement by LIPUS in rat cerebral cortex astrocytes. After LIPUS stimulation in astrocytes, the protein and mRNA expressions were measured by western blot and RT-PCR, respectively. The concentration of intracellular calcium was determined spectrophotometrically. The results showed that LIPUS enhanced the phosphorylation of tropomyosin-related kinase B (TrkB) and Akt but had no effect on Erk1/2 phosphorylation. Additionally, LIPUS increased the intracellular concentration of calcium and enhanced the protein levels of calmodulin-dependent kinase (CaMK) II and CaMKIV. LIPUS also activated the phosphorylation of NF-kappaB-p65 but did not promote the activation of cAMP response element-binding protein (CREB). Taken together, our results suggest that LIPUS stimulation upregulates BDNF production in astrocytes through the activation of NF-kappaB via the TrkB/PI3K/Akt and calcium/CaMK signaling pathways. BDNF has emerged as a major molecular player in the regulation of neural circuit development and function. Therefore, LIPUS stimulation may play a crucial and beneficial role in neurodegenerative diseases. PMID- 27252352 TI - Expression of Serotonin2C Receptors in Pyramidal and GABAergic Neurons of Rat Prefrontal Cortex: A Comparison with Striatum. AB - The prefrontal cortex (PFC) is enriched in several serotonin receptors, including 5-HT1A-R, 5-HT2A-R, and 5-HT3-R. These receptors modulate PFC activity due to their expression in large neuronal populations (5-HT1A-R, 5-HT2A-R) or in selected GABAergic populations (5-HT3-R). They are also relevant for antidepressant and antipsychotic drug action. Less is known about the localization of 5-HT2C-R, for which atypical antipsychotics show high affinity. Here, we report on the cellular distribution of 5-HT2C-R in rat PFC and striatum, using double in situ hybridization histochemistry. In PFC, 5-HT2C-R are expressed in pyramidal (VGLUT1-positive) and GABAergic (GAD-positive) neurons, including parvalbumin-positive neurons. There is a marked dorso-ventral gradient in the proportion of VGLUT1-positive cells expressing 5-HT2C-R (9% in the cingulate cortex, 61% in the tenia tecta and 66% in the piriform cortex), less marked for GABAergic neurons (13-27%). There is also a laminar gradient, with more cells expressing 5-HT2C-R in deep (V-VI) than in intermediate (II-III) layers. In common with 5-HT3-R, layer I GABAergic cells express 5-HT2C-R. The proportion of 5-HT2C-R-expressing striatal neurons was 23% (dorsolateral caudate-putamen), 37% (ventromedial caudate-putamen), 53% (nucleus accumbens-core), and 49% (nucleus accumbens-shell). These results help to better understand the serotonergic modulation of PFC-based networks, including basal ganglia circuits, and atypical antipsychotic drug action. PMID- 27252351 TI - Coding of Object Size and Object Category in Human Visual Cortex. AB - A salient aspect of objects is their real-world size. Large objects tend to be fixed in the world and can act as navigational barriers and landmarks, whereas small objects tend to be moveable and manipulable. Previous work has identified regions of visual cortex that respond differentially to large versus small objects, but the role of size in organizing representations of object categories has not been fully explored. To address this issue, we scanned subjects while they viewed large and small objects drawn from 20 categories, with retinotopic extent equated across size classes. Univariate analyses replicated previous results showing a greater response to large than small objects in scene responsive regions and the converse effect in the left occipitotemporal sulcus. Critically, multivariate analyses revealed organization-by-size both within and across functional regions, as evidenced by activation patterns that were more similar for object categories of the same size than for object categories of different size. This effect was observed in both scene- and object-responsive regions and across high-level visual cortex as a whole, but not in early visual cortex. We hypothesize that real-world size is an important dimension for object category organization because of the many ecologically significant differences between large and small objects. PMID- 27252350 TI - Stereoscopically Observing Manipulative Actions. AB - The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. PMID- 27252353 TI - Response Patterns of GABAergic Neurons in the Anterior Piriform Cortex of Awake Mice. AB - Local inhibition by gamma-amino butyric acid (GABA)-containing neurons is of vital importance for the operation of sensory cortices. However, the physiological response patterns of cortical GABAergic neurons are poorly understood, especially in the awake condition. Here, we utilized the recently developed optical tagging technique to specifically record GABAergic neurons in the anterior piriform cortex (aPC) in awake mice. The identified aPC GABAergic neurons were stimulated with robotic delivery of 32 distinct odorants, which covered a broad range of functional groups. We found that aPC GABAergic neurons could be divided into 4 types based on their response patterns. Type I, type II, and type III neurons displayed broad excitatory responses to test odorants with different dynamics. Type I neurons were constantly activated during odorant stimulation, whereas type II neurons were only transiently activated at the onset of odorant delivery. In addition, type III neurons displayed transient excitatory responses both at the onset and termination of odorant presentation. Interestingly, type IV neurons were broadly inhibited by most of the odorants. Taken together, aPC GABAergic neurons adopt different strategies to affect the cortical circuitry. Our results will allow for better understanding of the role of cortical GABAergic interneurons in sensory information processing. PMID- 27252354 TI - Inhibition of G9a/GLP Complex Promotes Long-Term Potentiation and Synaptic Tagging/Capture in Hippocampal CA1 Pyramidal Neurons. AB - Epigenetic regulations play an important role in regulating the learning and memory processes. G9a/G9a-like protein (GLP) lysine dimethyltransferase complex controls a prominent histone H3 lysine9 dimethylation (H3K9me2) that results in transcriptional silencing of the chromatin. Here, we report that the inhibition of G9a/GLP complex by either of the substrate competitive inhibitors UNC 0638 or BIX 01294 reinforces protein synthesis-independent long-term potentiation (early LTP) to protein synthesis-dependent long-term potentiation (late-LTP). The reinforcement effect was observed if the inhibitors were present during the induction of early-LTP and in addition when G9a/GLP complex inhibition was carried out by priming of synapses within an interval of 30 min before or after the induction of early-LTP. Surprisingly, the reinforced LTP by G9a/GLP complex inhibition was able to associate with a weak plasticity event from nearby independent synaptic populations, resulting in synaptic tagging/capture (STC). We have identified brain-derived neurotrophic factor (BDNF) as a critical plasticity protein that maintains G9a/GLP complex inhibition-mediated LTP facilitation and its STC. Our study reveals an epigenetic mechanism for promoting plasticity and associativity by G9a/GLP complex inhibition, and it may engender a promising epigenetic target for enhancing memory in neural networks. PMID- 27252355 TI - Investigating Mixture Interactions of Astringent Stimuli Using the Isobole Approach. AB - Astringents (alum, malic acid, tannic acid) representing 3 broad classes (multivalent salts, organic acids, and polyphenols) were characterized alone, and as 2- and 3-component mixtures using isoboles. In experiment 1, participants rated 7 attributes ("astringency," the sub-qualities "drying," "roughing," and "puckering," and the side tastes "bitterness," "sourness," and "sweetness") using direct scaling. Quality specific power functions were calculated for each stimulus. In experiment 2, the same participants characterized 2- and 3-component mixtures. Multiple factor analysis (MFA) and hierarchical clustering on attribute ratings across stimuli indicate "astringency" is highly related to "bitterness" as well as "puckering," and the subqualities "drying" and "roughing" are somewhat redundant. Moreover, power functions were used to calculate indices of interaction (I) for each attribute/mixture combination. For "astringency," there was evidence of antagonism, regardless of the type of mixture. Conversely, for subqualities, the pattern of interaction depended on the mixture type. Alum/tannic acid and tannic acid/malic acid mixtures showed evidence of synergy for "drying" and "roughing"; alum/malic acid mixtures showed evidence of antagonism for "drying," "roughing," and "puckering." Collectively, these data clarify some semantic ambiguity regarding astringency and its subqualities, as well as the nature of interactions of among different types of astringents. Present data are not inconsistent with the idea that astringency arises from multiple mechanisms, although it remains to be determined whether the synergy observed here might reflect simultaneous activation of these multiple mechanisms. PMID- 27252356 TI - Purification and Preparation of Rebaudioside A from Steviol Glycosides Using One Dimensional Hydrophilic Interaction Chromatography. AB - A method for purifying and preparing rebaudioside A (RA) from steviol glycosides at preparative scale was developed with resin based on hydrophilic interaction liquid chromatography (HILIC). In pure water and acetone-water system, the adsorption capacity and selectivity of five anion resins for RA, rebaudioside C (RC) and stevioside (ST) were examined and discussed. Strongly basic IRA458 with the quaternary amine group was chosen as the resin used for separating and preparing RA. The hydroxide form of IRA458 (IRA458-OH) showed the best results in terms of the adsorption behaviors for RA, RC and ST. The retentions of RA, RC and ST on IRA458-OH resin at high concentration of acetone solution followed HILIC mode, in which retention is probably based on surface adsorption of the resin. Under optimized chromatographic conditions, the pooled purity and yield of RA were up to 98.18 and 98.62%, the relative standard deviations (n = 3) for these two parameters were 1.2 and 5.7%, respectively. The present method has the characteristics of simple, low cost, high purity and high yield. The study will be a promising tool for RA industrialized production and also provides a possible mode for purifying and preparing polar components from their analogs. PMID- 27252357 TI - Exosomes secreted by mesenchymal stem cells promote endothelial cell angiogenesis by transferring miR-125a. AB - Angiogenesis plays crucial roles in various physiological processes including wound healing and tissue repair. It requires a tight interaction between endothelial cells and their surrounding environment. Mesenchymal stem cells (MSCs), one of the non-endothelial cell types present in the perivascular environment, have been shown to secret exosomes to modulate intercellular communications between MSCs and their target cells. In this study, we initially isolated exosomes secreted by human adipose-derived MSCs (adMSC-Exo) and examined their roles in angiogenesis. We found that adMSC-Exo could be taken up by endothelial cells and significantly promote angiogenesis in vitro and in vivo Further study showed that miR-125a was enriched in adMSC-Exo, and repressed the expression of the angiogenic inhibitor delta-like 4 (DLL4) by targeting its 3' untranslated region. Additionally, adMSC-Exo and its exosomal transferred miR 125a could repress DLL4 expression and modulate endothelial cell angiogenesis through promoting formation of endothelial tip cells. In conclusion, our study indicates that adMSC-Exo can transfer miR-125a to endothelial cells and promote angiogenesis by repressing DLL4. adMSC-Exo, as a pro-angiogenic factor, might be a promising candidate for therapeutical tissue repair. PMID- 27252358 TI - The endocytic activity of the flagellar pocket in Trypanosoma brucei is regulated by an adjacent phosphatidylinositol phosphate kinase. PMID- 27252359 TI - Additive Prognostic Value of Echocardiographic Global Longitudinal and Global Circumferential Strain to Electrocardiographic Criteria in Patients With Heart Failure Undergoing Cardiac Resynchronization Therapy. AB - BACKGROUND: Response to cardiac resynchronization therapy is most favorable in patients with heart failure with QRS duration >=150 ms and left bundle branch block and less predictable in those with QRS width 120 to 149 ms or non-left bundle branch block. METHODS AND RESULTS: We studied 205 patients with heart failure referred for cardiac resynchronization therapy with QRS >=120 ms and ejection fraction <=35%. We tested the hypothesis that contractile function using speckle-tracking echocardiographic global circumferential strain (GCS) from 2 short-axis views and global longitudinal strain (GLS) from 3 apical views add prognostic value to electrocardiographic criteria. There were 112 patients (55%) with GLS >-9% and 136 patients (66%) with GCS >-9%. During 4 years, 81 patients reached the combined primary end point (death, circulatory support, or transplant) and 120 reached the secondary end point (heart failure hospitalization or death). Both GLS >-9% and GCS >-9% were associated with increased risk of unfavorable events as follows: for the primary end point (hazard ratio=2.91; 95% confidence interval, 1.88-4.49; P<0.001) and (hazard ratio=3.73; 95% confidence interval, 2.39-5.82; P<0.001) for the secondary end point (hazard ratio=2.10; 95% confidence interval, 1.45-3.05; P<0.001) and (hazard ratio=3.25; 95% confidence interval, 2.23-4.75; P<0.001). In a prespecified subgroup of 120 patients with QRS 120 to 149 ms or non-left bundle branch block, significant associations of baseline GLS and GCS and outcomes remained: P=0.014 and P=0.002 for the primary end point and P=0.049 and P=0.001 for the secondary end point. Global strain measures had additive prognostic value to routine clinical or electrocardiographic parameters (P<0.001). CONCLUSIONS: Baseline GCS and GLS were significantly associated with long-term outcome after cardiac resynchronization therapy and had additive prognostic value to routine clinical and electrocardiographic selection criteria for cardiac resynchronization therapy. PMID- 27252360 TI - Echocardiographic Predictors of Response to Cardiac Resynchronization Therapy in 2016: Can Quantitative Global Parameters Succeed Where Segmental Parameters of Dyssynchrony Have Fallen Short? PMID- 27252361 TI - Protein Regulation in Signal Transduction. AB - SUMMARYCells must respond to a diverse, complex, and ever-changing mix of signals, using a fairly limited set of parts. Changes in protein level, protein localization, protein activity, and protein-protein interactions are critical aspects of signal transduction, allowing cells to respond highly specifically to a nearly limitless set of cues and also to vary the sensitivity, duration, and dynamics of the response. Signal-dependent changes in levels of gene expression and protein synthesis play an important role in regulation of protein levels, whereas posttranslational modifications of proteins regulate their degradation, localization, and functional interactions. Protein ubiquitylation, for example, can direct proteins to the proteasome for degradation or provide a signal that regulates their interactions and/or location within the cell. Similarly, protein phosphorylation by specific kinases is a key mechanism for augmenting protein activity and relaying signals to other proteins that possess domains that recognize the phosphorylated residues. PMID- 27252365 TI - A Rare Decade Where Magic Could Happen. PMID- 27252362 TI - Bone Morphogenetic Proteins. AB - Bone morphogenetic proteins (BMPs), originally identified as osteoinductive components in extracts derived from bone, are now known to play important roles in a wide array of processes during formation and maintenance of various organs including bone, cartilage, muscle, kidney, and blood vessels. BMPs and the related "growth and differentiation factors" (GDFs) are members of the transforming growth factor beta (TGF-beta) family, and transduce their signals through type I and type II serine-threonine kinase receptors and their intracellular downstream effectors, including Smad proteins. Furthermore, BMP signals are finely tuned by various agonists and antagonists. Because deregulation of the BMP activity at multiple steps in signal transduction is linked to a wide variety of human diseases, therapeutic use of activators and inhibitors of BMP signaling will provide potential avenues for the treatment of the human disorders that are caused by hypo- and hyperactivation of BMP signals, respectively. PMID- 27252367 TI - Biology of stress in poultry with emphasis on glucocorticoids and the heterophil to lymphocyte ratio. AB - The biology of stress in chickens is reviewed. Not only is stress associated with depressed production, but animal welfare influences consumer acceptance of poultry and eggs. The reciprocal of well-being is stress. The hypothalamo pituitary-adrenocortical axis in poultry consists of the neuropeptides, corticotropin releasing hormone, and arginine vasotocin that are released from the median eminence; the polypeptide hormone, adrenocorticotropic hormone (ACTH) secreted by the anterior pituitary gland; and the glucocorticoid hormone, corticosterone (CORT), synthesized by the adrenocortical cells. Many, but not all, stresses in chickens increase circulating concentrations of CORT. Circulating concentrations levels of CORT (both basal and in response to stressors) show marked differences in the literature, suggesting further attention is needed to ensure assays are validated for CORT in chicken plasma and other sources - excreta and feathers. As glucocorticoids influence the heterophil:lymphocyte (H:L) ratio, it is not surprising that the H:L is shifted with stress. It is recommended that close attention needs to be placed on the validity of assays including cross-laboratory standards. In addition, there is a strong case for determining multiple parameters of stress. PMID- 27252366 TI - Quantitative genetic analysis of causal relationships among feather pecking, feather eating, and general locomotor activity in laying hens using structural equation models. AB - The objective of this research was to analyze the relationship between feather pecking (FP) and feather eating (FE) as well as general locomotor activity (GLA) using structural equation models, which allow that one trait can be treated as an explanatory variable of another trait. This provides an opportunity to infer putative causal links among the traits. For the analysis, 897 F2-hens set up from 2 lines divergently selected for high and low FP were available. The FP observations were Box-Cox transformed, and FE and GLA observations were log and square root transformed, respectively. The estimated heritabilities of FE, GLA, and FP were 0.36, 0.29, and 0.20, respectively. The genetic correlation between FP and FE (GLA) was 0.17 (0.04). A high genetic correlation of 0.47 was estimated between FE and GLA. The recursive effect from FE to FP was [Formula: see text], and from GLA to FP [Formula: see text] These results imply that an increase of FE leads to an increased FP behavior and that an increase in GLA results in a higher FP value. Furthermore, the study showed that the genetic correlation among the traits is mainly caused by indirect effects. PMID- 27252368 TI - Survey of the prevalence of Salmonella species on laying hen farms in Kosovo. AB - A survey on the prevalence of Salmonella (S) species was carried out on 39 layer farms in Kosovo between April and September 2012. In total 367 samples, comprising feces, dust, eggs, and internal organs from dead birds, were investigated using bacteriological culture methods. Additionally, data on the location of the farm, the total number of birds on the farm, age of birds, and laying performance were collected. Salmonella were isolated from 38 samples obtained from 19 (49%) farms. The most common serovar identified was Salmonella enteritidis, found on 18 farms. The most common S. enteritidis phage type was PT29 followed by PT6, PT7, PT21, PT13a, PT8, PT14b, and PT4. One S. enteritidis isolate was not typable. Six farms had more than one phage type. Furthermore, serovar S. Bovismorbificans also was found in samples from 3 farms. Flock size or production stage was not associated with the probability of isolating Salmonella. The only flock factor found to be significantly associated was percent hen/day production: It was 2.8 times more likely to isolate Salmonella from flocks with production above 80% hen/day production compared to flocks producing at a lower level. Analysis of antimicrobial resistance patterns of 30 isolates revealed that all isolates were sensitive to gentamicin, ampicillin, sulphamethoxazole trimethoprim, and oxytetracycline, and 29 (97%) were sensitive to ciprofloxacin. All isolates showed intermediate resistance or were resistant to minocycline and cloxacillin. Twenty-six isolates (86%) had intermediate resistance to amoxicillin and 27 isolates (90%) were fully resistant to streptomycin. The present survey revealed a high prevalence of Salmonella enteritidis in layer flocks in Kosovo, indicating that table eggs have to be suspected as an important source of human salmone-llosis. PMID- 27252364 TI - Voltage-Gated Na+ Channels: Not Just for Conduction. AB - Voltage-gated sodium channels (VGSCs), composed of a pore-forming alpha subunit and up to two associated beta subunits, are critical for the initiation of the action potential (AP) in excitable tissues. Building on the monumental discovery and description of sodium current in 1952, intrepid researchers described the voltage-dependent gating mechanism, selectivity of the channel, and general structure of the VGSC channel. Recently, crystal structures of bacterial VGSC alpha subunits have confirmed many of these studies and provided new insights into VGSC function. VGSC beta subunits, first cloned in 1992, modulate sodium current but also have nonconducting roles as cell-adhesion molecules and function in neurite outgrowth and neuronal pathfinding. Mutations in VGSC alpha and beta genes are associated with diseases caused by dysfunction of excitable tissues such as epilepsy. Because of the multigenic and drug-resistant nature of some of these diseases, induced pluripotent stem cells and other novel approaches are being used to screen for new drugs and further understand how mutations in VGSC genes contribute to pathophysiology. PMID- 27252369 TI - Combined effects of Laminaria japonica and transglutaminase on physicochemical and sensory characteristics of semi-dried chicken sausages. AB - The effects of Laminaria japonica, Transglutaminase (TGase) and their combinations were investigated based on the physicochemical properties, textural properties, and sensory characteristics of semi-dried chicken sausages. The moisture content, ash content, and water activity of the semi-dried chicken sausage containing a combination of Laminaria japonica and TGase were higher than the control (P < 0.05). The semi-dried chicken sausage with 1.0% Laminaria japonica and 1.0% TGase (T3) had less cooking loss compared to the control and other treatments (P < 0.05). The protein content and fat content, pH of batters and sausages, springiness, and cohesiveness of the semi-dried chicken sausages were not significantly different between the control and treatments with a combination of Laminaria japonica and TGase (P > 0.05). Among the sensory traits, color score was highest in the control and in the treatment with 2.0% TGase (T5) (P < 0.05). The flavor score was highest in the control, while the treatments with 1.0% Laminaria japonica combined with 1.0% TGase (T3) had the highest tenderness and juiciness scores (P < 0.05). The results of this study show that the combination of Laminaria japonica and TGase successfully improved textural properties and sensory characteristics of the semi-dried chicken sausages, and the combination of 1.0% Laminaria japonica and 1.0% TGase improved quality of the semi-dried chicken sausages the most. PMID- 27252370 TI - Interactions between canola meal and flaxseed oil in the diets of White Lohmann hens on fatty acid profile and sensory characteristics of table eggs. AB - The current study was designed to assess the fatty acid composition and sensory attributes of eggs procured from hens consuming diets containing canola meal (CM) and/or flax oil (FO). A total of 96 group-caged White Lohmann hens received 1 of 4 isonitrogenous and isoenergetic diets for a period of 4 weeks. Diets were arranged in a 2 * 2 factorial design, containing 24% canola meal, 7.5% flax oil, both, or neither (control). All yolk fatty acids were affected by flax oil inclusion, with the exception of stearic acid (SA) and docosapentaenoic acid (DPA). Only SA was affected by CM inclusion. Additionally, significant interactions between CM and FO were observed for linoleic acid (LA) and total omega-6 polyunsaturated fatty acids (PUFA), with DPA approaching significance (P = 0.069). Trained panelists (n = 8) evaluated 7 aroma ('egg', 'creamy', 'buttery', 'salty', 'sweet', 'barny', and 'oceanic') and 6 flavor ('egg', 'creamy', 'buttery', 'salty', 'brothy', and 'oceanic') attributes of cooked egg product. No significant differences (P > 0.05) in aroma attributes were found between eggs from different dietary treatments. However, egg, creamy, buttery, and oceanic flavors were significantly different between the dietary treatments (P < 0.05). While oceanic flavor significantly increased with inclusion of FO, egg and creamy flavors showed a significant decrease (P < 0.05). Although CM addition alone did not result in significant sensory changes, the pairing of CM and FO resulted in even greater sensory changes than using FO alone, specifically with regard to egg flavor. Results from partial least squares analyses showed a strong association between oceanic flavor and omega-3 PUFA. Oppositely, egg, creamy, and buttery flavors were more correlated with the presence of omega-6 PUFA and palmitic acid. This experiment provides evidence that the interaction between CM and FO in the White Lohmann hen diet results in sensory changes of cooked eggs associated in part with changes in yolk fatty acid content. PMID- 27252363 TI - Regulation of the Bioavailability of TGF-beta and TGF-beta-Related Proteins. AB - The bioavailability of members of the transforming growth factor beta (TGF-beta) family is controlled by a number of mechanisms. Bona fide TGF-beta is sequestered into the matrix in a latent state and must be activated before it can bind to its receptors. Here, we review the molecules and mechanisms that regulate the bioavailability of TGF-beta and compare these mechanisms with those used to regulate other TGF-beta family members. We also assess the physiological significance of various latent TGF-beta activators, as well as other extracellular modulators of TGF-beta family signaling, by examining the available in vivo data from knockout mouse models and other biological systems. PMID- 27252371 TI - The efficacy of dietary xylanase and phytase in broiler chickens fed expeller extracted camelina meal. AB - A study was conducted to investigate the effects of dietary phytase (PHY) and xylanase (XYL) on growth performance, nutrient utilization, and intestinal characteristics in broilers fed corn-soybean meal-based diets with added expeller extracted camelina meal (CM). The corn-soybean meal-based diets without or with CM was formulated to contain 2.9 or 2.7 g/kg non phytate phosphorus, respectively. A total of 384 male Ross 708 broilers were allocated to 8 dietary treatments in a randomized complete block design with 6 replicates per treatment, from 7 to 21 d post hatching. The experiment consisted of a 2 * 2 * 2 factorial arrangement of treatments with 2 dietary CM levels (zero or 100 g/kg), 2 dietary levels of XYL (zero or 800 unit/kg), and 2 dietary levels of PHY (zero or 4,000 unit/kg). Chromic oxide was included in the diets as an indigestible marker. Growth was measured throughout the experiment and excreta were collected on d 18 to 21 post hatching for measurement of nutrient and energy retention. On d 21 post hatching, broilers were euthanized by CO2 asphyxiation, ileal digesta was collected for nutrient and energy digestibility measurements, and the left tibia was removed for bone ash measurement. Furthermore, duodenal digesta was collected and a segment of the mid jejunum was excised for viscosity and morphology measurement, respectively. Broilers fed 100 g/kg CM diets showed lower (P < 0.001) BW gain and G:F than those fed zero g/kg CM diets for 7 to 14 d and 7 to 21 d post hatching periods, respectively. Phytase supplementation improved (P < 0.05) all the growth parameters measured regardless of CM addition. Phytase supplementation resulted in an increase (P < 0.05) in jejunum villus height but there was no impact of CM or XYL. Additionally, duodenal digesta viscosity increased (P < 0.001) with added CM. Tibia ash and weight increased (P < 0.001) with PHY supplementation. There was a CM * PHY interaction (P < 0.05) on percentage tibia ash, with greater PHY effect in zero g/kg CM diets compared with 100 g/kg CM diets. Phytase supplementation increased (P < 0.05) ileal DM, N, energy, P, and neutral detergent fiber (NDF) digestibility. In diets with 100 g/kg CM, addition of PHY had a greater effect (CM * PHY; P < 0.05) on ileal P digestibility compared with diet without CM. There was a CM * PHY interaction (P < 0.05) for ileal digestible energy (IDE) in which PHY increased the IDE in birds fed CM supplemented diets. Both ileal digestibility and retentions of DM, N, energy, and IDE, AME, and AMEn were decreased (P < 0.05) by CM supplementation. Retention of ether extract and NDF decreased (P < 0.05) with CM supplementation. Nitrogen retention, AME, and AMEn decreased (CM * XYL; P < 0.05) with XYL supplementation in zero g/kg CM diets. There were CM * XYL interactions (P < 0.01) for P and Ca retentions in which XYL increased retentions in 100 g/kg CM diets. In conclusion, PHY was efficacious at improving P digestibility and retention of birds fed low P corn-soy based diets without or with CM. However, regardless of CM addition, XYL did not improve nutrient utilization and growth performance of broiler chickens. The present data also show that the mechanism underlying the detrimental effects of CM inclusion on nutrient utilization is not mediated through gut morphology and goblet cell density. The data also show that the villus height increase occurring with PHY addition might be a contributor to the improvements in ileal DM, N, and energy digestibility obtained with PHY supplementation. PMID- 27252372 TI - Peach skin powder inhibits oxidation in cooked turkey meat. AB - The objective of this study was to measure the antioxidant activity of peach skin and test the antioxidant effect of peach skin powder on cooked ground turkey meat during 12 d of refrigerated storage. Antioxidant activity of 3 cultivars of peaches grown in South Carolina was first evaluated by 3 antioxidant assays. The peach variety O'Henry showed the greatest antioxidant effect and therefore was used for further study. Two levels of peach skin powder (0.5%, 1%) and 0.01% butylated hydroxylanisole (BHA) were applied to ground turkey meat. Oxidation of cooked turkey meat was measured by detection of hexanal using gas chromatography mass spectrometry. Results indicated that all levels of peach skin powder used in this study had an antioxidant effect on ground turkey with a greater effect at the higher concentration. O'Henry peach skin powder was as effective as BHA in preventing oxidation at the levels tested. PMID- 27252373 TI - Inactivation of Salmonella enteritidis on shell eggs by coating with phytochemicals. AB - Salmonella enteritidis (SE) is a major foodborne pathogen that causes human infections largely by consumption of contaminated eggs. The external surface of eggs becomes contaminated with SE from multiple sources, highlighting the need for effective egg surface disinfection methods. This study investigated the efficacy of three GRAS-status, phytochemicals, namely carvacrol (CR), eugenol (EG), and beta-resorcylic acid (BR) applied as pectin or gum arabic based coating for reducing SE on shell eggs. White-shelled eggs, spot inoculated with a 5 strain mixture of nalidixic acid (NA) resistant SE (8.0 log CFU/mL) were coated with pectin or gum arabic solution containing each phytochemical (0.0, 0.25, 0.5, or 0.75%), and stored at 4 degrees C for 7 days. SE on eggs was enumerated on days 0, 1, 3, and 7 of storage. Approximately 4.0 log CFU/egg of SE was recovered from inoculated and pectin or gum arabic coated eggs on day 0. All coating treatments containing CR and EG, and BR at 0.75% reduced SE to undetectable levels on day 3 (P < 0.05). Results suggest that the aforementioned phytochemicals could effectively be used as a coating to reduce SE on shell eggs, but detailed studies on the sensory and quality attributes of coated eggs need to be conducted before recommending their use. PMID- 27252374 TI - The immunomodulatory effect of vitamin D in chickens is dose-dependent and influenced by calcium and phosphorus levels. AB - Vitamin D requirement is estimated to be higher than recommended values for the first two weeks of a broiler chicken's life, and is heavily dependent on the concentrations of Ca and P in the diet. There are data indicating the beneficial effect of higher vitamin D levels on performance and overall health of the chickens. However, data on the role of higher vitamin D levels on the innate immune response of chickens are limited. Therefore, in the current study, we examined the effect of higher doses of vitamin D supplementation on the innate immune response in broiler chickens receiving optimal or calcium (Ca) and phosphorus (P) deficient diets. Three hundred Ross-308 male broiler chicks were randomly allocated into 60 cages with 5 birds per cage in a 3 * 2 factorial design with three levels of vitamin D and two levels of Ca/P with each experimental diet fed to 10 cages (10 replicates). Quantitative reverse transcription PCR (n = 5) was used to assess Toll-like receptor (TLR2b and 4), cytokine/chemokine (IL-12, IFN-gamma, IL-10, IL-4, IL-13, IL-18, CxCLi2) and cathelicidin (CATH1, CATHB1, CATH3) transcription levels in peripheral blood mononuclear cells (PBMCs), spleen, and bursa of Fabricius. Vitamin D supplementation of the Ca and P deficient diet considerably augmented transcription of TLR2b, TLR4, CATH1, and CATHB1 and predominantly Th2 cytokines in spleen. Supplementation of the control diet with vitamin D downregulated TLR4 transcription, and dose-dependently increased CATH1, CATHB1, Th1, and Th2 cytokine transcription (Th2>Th1). All diets downregulated CATH3 transcription. In conclusion, vitamin D or its derivative 25-OH-D3 both have a robust immunomodulatory property with a more favorable Th2 response, while at the same time enhancing observed Th2 cytokine responses under both optimal and lower Ca and P inclusion levels in the diets of broiler chickens. PMID- 27252375 TI - The G1 Cyclin-dependent Kinase CRK1 in Trypanosoma brucei Regulates Anterograde Protein Transport by Phosphorylating the COPII Subunit Sec31. AB - Transport of secretory proteins from the endoplasmic reticulum to the Golgi is mediated by the coat protein II (COPII) complex comprising a Sec23-Sec24 heterodimer and a Sec13-Sec31 heterotetramer. The mechanisms underlying COPII mediated protein trafficking have been well defined, but the extent of regulation of this secretory machinery by cellular signaling pathways remains poorly understood. Here, we report that CRK1, a G1 cyclin-dependent kinase in Trypanosoma brucei, regulates anterograde protein trafficking by phosphorylating Sec31. Depletion of CRK1 abolished anterograde transport of the secretory protein and disrupted the localization of multiple Golgi proteins, reminiscent of Sec31 depletion. CRK1 phosphorylates Sec31 at multiple serine/threonine sites, and mutation of these phosphosites to alanine recapitulates the protein trafficking defects caused by Sec31 depletion. Mutation of these CRK1 phosphosites to aspartate restored Sec31 function. Taken together, these results uncover a novel function of CRK1 in anterograde protein trafficking and elucidate the mechanistic role of CRK1 in protein trafficking through regulation of the COPII subunit Sec31. PMID- 27252376 TI - Light-harvesting Complexes (LHCs) Cluster Spontaneously in Membrane Environment Leading to Shortening of Their Excited State Lifetimes. AB - The light reactions of photosynthesis, which include light-harvesting and charge separation, take place in the amphiphilic environment of the thylakoid membrane. The light-harvesting complex II (LHCII) is the main responsible for light absorption in plants and green algae and is involved in photoprotective mechanisms that regulate the amount of excited states in the membrane. The dual function of LHCII has been extensively studied in detergent micelles, but recent results have indicated that the properties of this complex differ in a lipid environment. In this work we checked these suggestions by studying LHCII in liposomes. By combining bulk and single molecule measurements, we monitored the fluorescence characteristics of liposomes containing single complexes up to densely packed proteoliposomes. We show that the natural lipid environment per se does not alter the properties of LHCII, which for single complexes remain very similar to that in detergent. However, we show that LHCII has the strong tendency to cluster in the membrane and that protein interactions and the extent of crowding modulate the lifetimes of the excited state in the membrane. Finally, the presence of LHCII monomers at low concentrations of complexes per liposome is discussed. PMID- 27252377 TI - Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation. AB - The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU- and beta-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPA-mediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp 1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus. PMID- 27252378 TI - Identification of a Noroxomaritidine Reductase with Amaryllidaceae Alkaloid Biosynthesis Related Activities. AB - Amaryllidaceae alkaloids are a large group of plant natural products with over 300 documented structures and diverse biological activities. Several groups of Amaryllidaceae alkaloids including the hemanthamine- and crinine-type alkaloids show promise as anticancer agents. Two reduction reactions are required for the production of these compounds: the reduction of norcraugsodine to norbelladine and the reduction of noroxomaritidine to normaritidine, with the enantiomer of noroxomaritidine dictating whether the derivatives will be the crinine-type or hemanthamine-type. It is also possible for the carbon-carbon double bond of noroxomaritidine to be reduced, forming the precursor for maritinamine or elwesine depending on the enantiomer reduced to an oxomaritinamine product. In this study, a short chain alcohol dehydrogenase/reductase that co-expresses with the previously discovered norbelladine 4'-O-methyltransferase from Narcissus sp. and Galanthus spp. was cloned and expressed in Escherichia coli Biochemical analyses and x-ray crystallography indicates that this protein functions as a noroxomaritidine reductase that forms oxomaritinamine from noroxomaritidine through a carbon-carbon double bond reduction. The enzyme also reduces norcraugsodine to norbelladine with a 400-fold lower specific activity. These studies identify a missing step in the biosynthesis of this pharmacologically important class of plant natural products. PMID- 27252379 TI - Solution Structures of Complement C2 and Its C4 Complexes Propose Pathway specific Mechanisms for Control and Activation of the Complement Proconvertases. AB - The lectin (LP) and classical (CP) pathways are two of the three main activation cascades of the complement system. These pathways start with recognition of different pathogen- or danger-associated molecular patterns and include identical steps of proteolytic activation of complement component C4, formation of the C3 proconvertase C4b2, followed by cleavage of complement component C2 within C4b2 resulting in the C3 convertase C4b2a. Here, we describe the solution structures of the two central complexes of the pathways, C3 proconvertase and C3 convertase, as well as the unbound zymogen C2 obtained by small angle x-ray scattering analysis. We analyzed both native and enzymatically deglycosylated C4b2 and C2 and showed that the resulting structural models were independent of the glycans. The small angle x-ray scattering-derived models suggest a different activation mode for the CP/LP C3 proconvertase as compared with that established for the alternative pathway proconvertase C3bB. This is likely due to the rather different structural and functional properties of the proteases activating the proconvertases. The solution structure of a stabilized form of the active CP/LP C3 convertase C4b2a is strikingly similar to the crystal structure of the alternative pathway C3 convertase C3bBb, which is in accordance with their identical functions in cleaving the complement proteins C3 and C5. PMID- 27252380 TI - 1,2-Propanediol Dehydration in Roseburia inulinivorans: STRUCTURAL BASIS FOR SUBSTRATE AND ENANTIOMER SELECTIVITY. AB - Glycyl radical enzymes (GREs) represent a diverse superfamily of enzymes that utilize a radical mechanism to catalyze difficult, but often essential, chemical reactions. In this work we present the first biochemical and structural data for a GRE-type diol dehydratase from the organism Roseburia inulinivorans (RiDD). Despite high sequence (48% identity) and structural similarity to the GRE-type glycerol dehydratase from Clostridium butyricum, we demonstrate that the RiDD is in fact a diol dehydratase. In addition, the RiDD will utilize both (S)-1,2 propanediol and (R)-1,2-propanediol as a substrate, with an observed preference for the S enantiomer. Based on the new structural information we developed and successfully tested a hypothesis that explains the functional differences we observe. PMID- 27252381 TI - Phosphorylation Interferes with Maturation of Amyloid-beta Fibrillar Structure in the N Terminus. AB - Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-beta (Abeta) peptide and investigate how phosphorylation at serine 8 affects the structure of Abeta aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric Abeta, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that Abeta phosphorylation at serine 8 causes structural changes in the N-terminal region of Abeta aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of Abeta aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration. PMID- 27252383 TI - CCN6 regulates mitochondrial function. AB - Despite established links of CCN6, or Wnt induced signaling protein-3 (WISP3), with progressive pseudo rheumatoid dysplasia, functional characterization of CCN6 remains incomplete. In light of the documented negative correlation between accumulation of reactive oxygen species (ROS) and CCN6 expression, we investigated whether CCN6 regulates ROS accumulation through its influence on mitochondrial function. We found that CCN6 localizes to mitochondria, and depletion of CCN6 in the chondrocyte cell line C-28/I2 by using siRNA results in altered mitochondrial electron transport and respiration. Enhanced electron transport chain (ETC) activity of CCN6-depleted cells was reflected by increased mitochondrial ROS levels in association with augmented mitochondrial ATP synthesis, mitochondrial membrane potential and Ca(2+) Additionally, CCN6 depleted cells display ROS-dependent PGC1alpha (also known as PPARGC1A) induction, which correlates with increased mitochondrial mass and volume density, together with altered mitochondrial morphology. Interestingly, transcription factor Nrf2 (also known as NFE2L2) repressed CCN6 expression. Taken together, our results suggest that CCN6 acts as a molecular brake, which is appropriately balanced by Nrf2, in regulating mitochondrial function. PMID- 27252382 TI - TFEB at a glance. AB - The transcription factor EB (TFEB) plays a pivotal role in the regulation of basic cellular processes, such as lysosomal biogenesis and autophagy. The subcellular localization and activity of TFEB are regulated by mechanistic target of rapamycin (mTOR)-mediated phosphorylation, which occurs at the lysosomal surface. Phosphorylated TFEB is retained in the cytoplasm, whereas dephosphorylated TFEB translocates to the nucleus to induce the transcription of target genes. Thus, a lysosome-to-nucleus signaling pathway regulates cellular energy metabolism through TFEB. Recently, in vivo studies have revealed that TFEB is also involved in physiological processes, such as lipid catabolism. TFEB has attracted a lot of attention owing to its ability to induce the intracellular clearance of pathogenic factors in a variety of murine models of disease, such as Parkinson's and Alzheimer's, suggesting that novel therapeutic strategies could be based on the modulation of TFEB activity. In this Cell Science at a Glance article and accompanying poster, we present an overview of the latest research on TFEB function and its implication in human diseases. PMID- 27252384 TI - Organelle size control - increasing vacuole content activates SNAREs to augment organelle volume through homotypic fusion. AB - Cells control the size of their compartments relative to cell volume, but there is also size control within each organelle. Yeast vacuoles neither burst nor do they collapse into a ruffled morphology, indicating that the volume of the organellar envelope is adjusted to the amount of content. It is poorly understood how this adjustment is achieved. We show that the accumulating content of yeast vacuoles activates fusion of other vacuoles, thus increasing the volume-to surface ratio. Synthesis of the dominant compound stored inside vacuoles, polyphosphate, stimulates binding of the chaperone Sec18/NSF to vacuolar SNAREs, which activates them and triggers fusion. SNAREs can only be activated by lumenal, not cytosolic, polyphosphate (polyP). Control of lumenal polyP over SNARE activation in the cytosol requires the cytosolic cyclin-dependent kinase Pho80-Pho85 and the R-SNARE Nyv1. These results suggest that cells can adapt the volume of vacuoles to their content through feedback from the vacuole lumen to the SNAREs on the cytosolic surface of the organelle. PMID- 27252385 TI - Endosomal assembly and transport of heteromeric septin complexes promote septin cytoskeleton formation. AB - Septins are conserved cytoskeletal structures functioning in a variety of biological processes including cytokinesis and cell polarity. A wealth of information exists on the heterooligomeric architecture of septins and their subcellular localization at distinct sites. However, the precise mechanisms of their subcellular assembly and their intracellular transport are unknown. Here, we demonstrate that endosomal transport of septins along microtubules is crucial for formation of higher-order structures in the fungus Ustilago maydis Importantly, endosomal septin transport is dependent on each individual septin providing strong evidence that septin heteromeric complexes are assembled on endosomes. Furthermore, endosomal trafficking of all four septin mRNAs is required for endosomal localization of their translation products. Based on these results, we propose that local translation promotes the assembly of newly synthesized septins in heteromeric structures on the surface of endosomes. This is important for the long-distance transport of septins and the efficient formation of the septin cytoskeleton. PMID- 27252386 TI - Substrate specificity and mapping of residues critical for transport in the high affinity glutathione transporter Hgt1p. AB - The high-affinity glutathione transporter Hgt1p of Saccharomyces cerevisiae belongs to a relatively new and structurally uncharacterized oligopeptide transporter (OPT) family. To understand the structural features required for interaction with Hgt1p, a quantitative investigation of substrate specificity of Hgt1p was carried out. Hgt1p showed a higher affinity for reduced glutathione (GSH), whereas it transported oxidized glutathione (GSSG) and other glutathione conjugates with lower affinity. To identify the residues of Hgt1p critical for substrate binding and translocation, all amino acid residues of the 13 predicted transmembrane domains (TMDs) have been subjected to mutagenesis. Functional evaluation of these 269 mutants by growth and biochemical assay followed by kinetic analysis of the severely defective mutants including previous mutagenic studies on this transporter have led to the identification of N124 (TMD1), V185 (TMD3), Q222, G225 and Y226 (TMD4), P292 (TMD5), Y374 (TMD6), L429 (TMD7) and F523 and Q526 (TMD9) as critical for substrate binding with at least 3-fold increase in Km upon mutagenesis to alanine. In addition residues Y226 and Y374 appeared to be important for differential substrate specificity. An ab initio model of Hgt1p was built and refined using these mutagenic data that yielded a helical arrangement that includes TMD3, TMD4, TMD5, TMD6, TMD7, TMD9 and TMD13 as pore-lining helices with the functionally important residues in a channel-facing orientation. Taken together the results of this study provides the first mechanistic insights into glutathione transport by a eukaryotic high-affinity glutathione transporter. PMID- 27252387 TI - Discovery, characterization and in vivo activity of pyocin SD2, a protein antibiotic from Pseudomonas aeruginosa. AB - Increasing rates of antibiotic resistance among Gram-negative pathogens such as Pseudomonas aeruginosa means alternative approaches to antibiotic development are urgently required. Pyocins, produced by P. aeruginosa for intraspecies competition, are highly potent protein antibiotics known to actively translocate across the outer membrane of P. aeruginosa. Understanding and exploiting the mechanisms by which pyocins target, penetrate and kill P. aeruginosa is a promising approach to antibiotic development. In this work we show the therapeutic potential of a newly identified tRNase pyocin, pyocin SD2, by demonstrating its activity in vivo in a murine model of P. aeruginosa lung infection. In addition, we propose a mechanism of cell targeting and translocation for pyocin SD2 across the P. aeruginosa outer membrane. Pyocin SD2 is concentrated at the cell surface, via binding to the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide (LPS), from where it can efficiently locate its outer membrane receptor FpvAI. This strategy of utilizing both the CPA and a protein receptor for cell targeting is common among pyocins as we show that pyocins S2, S5 and SD3 also bind to the CPA. Additional data indicate a key role for an unstructured N-terminal region of pyocin SD2 in the subsequent translocation of the pyocin into the cell. These results greatly improve our understanding of how pyocins target and translocate across the outer membrane of P. aeruginosa. This knowledge could be useful for the development of novel anti-pseudomonal therapeutics and will also support the development of pyocin SD2 as a therapeutic in its own right. PMID- 27252389 TI - Obesity, hypertension and aldosterone: is leptin the link? AB - Obesity is a serious health hazard with rapidly increasing prevalence in the United States. In 2014, the World Health Organization estimated that nearly 2 billion people worldwide were overweight with an estimated 600 million of these obese. Obesity is associated with many chronic diseases, including cardiovascular disease and hypertension. Data from the Framingham Heart study suggest that approximately 78% of the risk for hypertension in men and 65% in women is related to excess body weight, a relationship that is further supported by studies showing increases in blood pressure with weight gain and decreases with weight loss. However, the exact mechanism by which excess body fat induces hypertension remains poorly understood. Several clinical studies have demonstrated elevated plasma aldosterone levels in obese individuals, especially those with visceral adiposity, with decreased aldosterone levels measured in concert with reduced blood pressure following weight loss. Since aldosterone is a mineralocorticoid hormone that regulates blood volume and pressure, serum aldosterone levels may link obesity and hypertension. Nevertheless, the mechanism by which obesity induces aldosterone production is unclear. A recent study by Belin de Chantemele and coworkers suggests that one adipose-released factor, leptin, is a direct agonist for aldosterone secretion; other adipose-related factors may also contribute to elevated aldosterone levels in obesity, such as very low-density lipoprotein (VLDL), the levels of which are elevated in obesity and which also directly stimulates aldosterone biosynthesis. This focused review explores the possible roles of leptin and VLDL in modulating aldosterone secretion to underlie obesity-associated hypertension. PMID- 27252388 TI - Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study. AB - RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk. METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ~ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68-1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84-1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis. PMID- 27252395 TI - The Prehistory of Antibiotic Resistance. AB - Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. PMID- 27252398 TI - Colonization Dynamics of Subcortical Insects on Forest Sites With Relatively Stressed and Unstressed Loblolly Pine Trees. AB - Loblolly pine (Pinus taeda L.) is the most important commercial tree species in the southeastern United States. Since the 1950s, there have been reports of loblolly pines showing reduced growth and increased mortality, particularly in central Alabama and western Georgia, United States; the phenomenon is termed as southern pine decline (SPD). Recently, the role of rhizophagous (root-feeding) insects in loblolly pine health within the context of SPD has come under greater scrutiny. We investigated the impacts of subcortical insects, particularly rhizophagous weevils (Coleoptera: Curculionidae), on loblolly pine health in northeastern Georgia. We created plots-representing a gradient of increased relative tree stress-from ungirdled trees, ungirdled trees baited with ethanol and turpentine (ungirdled-baited), and girdled trees. In total, 10,795 subcortical insects from four families (Buprestidae, Cerambycidae, Curculionidae, and Siricidae) and >82 species were trapped in two years. Almost half of the insects trapped (46% of individuals and 11% of species) were nonnative to North America. Insect captures in plots with girdled trees were 61 and 187% greater than those with ungirdled-baited and ungirdled trees, respectively. Tree treatment impacted captures of native, but not nonnative insects. Relative feeding area by the rhizophagous weevils Hylobius pales (Herbst) and Pachylobius picivorus (Germar) on pine twigs placed in pitfall traps was 1, 17, and 82% in plots with ungirdled, ungirdled-baited, and girdled trees, respectively. Hence, there was a strong association of native subcortical insects, especially rhizophagous weevils, with relatively highly stressed trees, confirming that they are secondary instead of primary pine colonizers. PMID- 27252397 TI - Aminoglycosides: An Overview. AB - Aminoglycosides are natural or semisynthetic antibiotics derived from actinomycetes. They were among the first antibiotics to be introduced for routine clinical use and several examples have been approved for use in humans. They found widespread use as first-line agents in the early days of antimicrobial chemotherapy, but were eventually replaced in the 1980s with cephalosporins, carbapenems, and fluoroquinolones. Aminoglycosides synergize with a variety of other antibacterial classes, which, in combination with the continued increase in the rise of multidrug-resistant bacteria and the potential to improve the safety and efficacy of the class through optimized dosing regimens, has led to a renewed interest in these broad-spectrum and rapidly bactericidal antibacterials. PMID- 27252396 TI - Genome Stability Requires p53. AB - It is now clear that functional p53 is critical to protect the genome from alterations that lead to tumorigenesis. However, with the myriad of cellular stresses and pathways linked to p53 activation, much remains unknown about how p53 maintains genome stability and the proteins involved. The current understanding of the multiple ways p53 contributes to genome stability and how two of its negative regulators, Mdm2 and Mdmx, induce genome instability will be described. PMID- 27252399 TI - Integration of new alternative reference strain genome sequences into the Saccharomyces genome database. AB - The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org/) is the authoritative community resource for the Saccharomyces cerevisiae reference genome sequence and its annotation. To provide a wider scope of genetic and phenotypic variation in yeast, the genome sequences and their corresponding annotations from 11 alternative S. cerevisiae reference strains have been integrated into SGD. Genomic and protein sequence information for genes from these strains are now available on the Sequence and Protein tab of the corresponding Locus Summary pages. We illustrate how these genome sequences can be utilized to aid our understanding of strain-specific functional and phenotypic differences.Database URL: www.yeastgenome.org. PMID- 27252400 TI - An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab. AB - Vedolizumab is a novel therapeutic monoclonal antibody recently approved for the treatment of moderately to severely active ulcerative colitis and Crohn's disease in adults who have failed at least one conventional therapy. An integrin antagonist, vedolizumab binds to the alpha4beta7 integrin which is expressed specifically by a subset of gastrointestinal-homing T lymphocytes. The binding of alpha4beta7 integrin to mucosal addressin cell adhesion molecule-1 expressed on the surface of mucosal endothelial cells is a crucial component of the gut selective homing mechanism for lymphocytes.In contrast, other monoclonal antibodies approved for the treatment of inflammatory bowel diseases, such as tumour necrosis factor alpha antagonists and the integrin antagonist natalizumab, act systemically or on multiple targets to reduce inflammation.The unique gut selectivity of vedolizumab may contribute to the favourable benefit-risk profile observed in vedolizumab clinical trials. In this review, we summarise data from the preclinical development of vedolizumab and describe the current understanding of the mechanism of action as it relates to other biological therapies for inflammatory bowel disease. PMID- 27252402 TI - Sex and gender differences in chronic kidney disease: progression to end-stage renal disease and haemodialysis. AB - Sex and gender differences are of fundamental importance in most diseases, including chronic kidney disease (CKD). Men and women with CKD differ with regard to the underlying pathophysiology of the disease and its complications, present different symptoms and signs, respond differently to therapy and tolerate/cope with the disease differently. Yet an approach using gender in the prevention and treatment of CKD, implementation of clinical practice guidelines and in research has been largely neglected. The present review highlights some sex- and gender specific evidence in the field of CKD, starting with a critical appraisal of the lack of inclusion of women in randomized clinical trials in nephrology, and thereafter revisits sex/gender differences in kidney pathophysiology, kidney disease progression, outcomes and management of haemodialysis care. In each case we critically consider whether apparent discrepancies are likely to be explained by biological or psycho-socioeconomic factors. In some cases (a few), these findings have resulted in the discovery of disease pathways and/or therapeutic opportunities for improvement. In most cases, they have been reported as merely anecdotal findings. The aim of the present review is to expose some of the stimulating hypotheses arising from these observations as a preamble for stricter approaches using gender for the prevention and treatment of CKD and its complications. PMID- 27252403 TI - Bacterial pathogen gene regulation: a DNA-structure-centred view of a protein dominated domain. AB - The mechanisms used by bacterial pathogens to regulate the expression of their genes, especially their virulence genes, have been the subject of intense investigation for several decades. Whole genome sequencing projects, together with more targeted studies, have identified hundreds of DNA-binding proteins that contribute to the patterns of gene expression observed during infection as well as providing important insights into the nature of the gene products whose expression is being controlled by these proteins. Themes that have emerged include the importance of horizontal gene transfer to the evolution of pathogens, the need to impose regulatory discipline upon these imported genes and the important roles played by factors normally associated with the organization of genome architecture as regulatory principles in the control of virulence gene expression. Among these architectural elements is the structure of DNA itself, its variable nature at a topological rather than just at a base-sequence level and its ability to play an active (as well as a passive) part in the gene regulation process. PMID- 27252404 TI - Mitochondrial [dys]function; culprit in pre-eclampsia? AB - Mitochondria are extensively identified for their bioenergetic capacities; however, recently these metabolic hubs are increasingly being appreciated as critical regulators of numerous cellular signalling systems. Mitochondrial reactive oxygen species have evolved as a mode of cross-talk between mitochondrial function and physiological systems, to sustain equipoise and foster adaption to cellular stress. Redox signalling mediated by exaggerated mitochondrial-ROS (reactive oxygen species) has been incriminated in a plethora of disease pathologies. Excessive production of mitochondrial ROS is intrinsically linked to mitochondrial dysfunction. Furthermore, mitochondrial dysfunction is a key facilitator of oxidative stress, inflammation, apoptosis and metabolism. These are key pathogenic intermediaries of pre-eclampsia, hence we hypothesize that mitochondrial dysfunction is a pathogenic mediator of oxidative stress in the pathophysiology of pre-eclampsia. We hypothesize that mitochondrial targeted antioxidants may restrain production of ROS-mediated deleterious redox signalling pathways. If our hypothesis proves correct, therapeutic strategies directly targeting mitochondrial superoxide scavenging should be actively pursued as they may alleviate maternal vascular dysfunction and dramatically improve maternal and fetal health worldwide. PMID- 27252401 TI - miRNAs in NMDA receptor-dependent synaptic plasticity and psychiatric disorders. AB - The identification and functional delineation of miRNAs (a class of small non coding RNAs) have added a new layer of complexity to our understanding of the molecular mechanisms underlying synaptic plasticity. Genome-wide association studies in conjunction with investigations in cellular and animal models, moreover, provide evidence that miRNAs are involved in psychiatric disorders. In the present review, we examine the current knowledge about the roles played by miRNAs in NMDA (N-methyl-D-aspartate) receptor-dependent synaptic plasticity and psychiatric disorders. PMID- 27252405 TI - Adiponectin promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-27b through a CaMKII/AMPK/p38 signaling pathway in human chondrosarcoma cells. AB - Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis. PMID- 27252407 TI - Ant Foraging As an Indicator of Tropical Dry Forest Restoration. AB - Variation in foraging behavior may indicate differences in food availability and allow assessment of restoration actions. Ants are prominent bioindicators used in assessing ecological responses to disturbance. However, behavioral data have been poorly incorporated as an index. The foraging performance of red harvester ants was quantified in order to evaluate the success of a restoration ecology experiment in the tropical dry forest of Sierra de Huautla, Morelos, in central Mexico. Foraging performance by granivorous, Pogonomyrmex barbatus, ants was diminished after 6 and 8 years of cattle grazing and wood harvest were excluded as part of a restoration experiment in a highly degraded biome. Despite investing more time in foraging, ant colonies in exclusion plots showed lower foraging success and acquired less seed biomass than colonies in control plots. In line with the predictions of optimal foraging theory, in restored plots where ant foraging performance was poor, ants harvested a higher diversity of seeds. Reduced foraging success and increased harvest of non-preferred foods in exclusion plots were likely due to the growth of herbaceous vegetation, which impedes travel by foragers. Moreover, by 8 years of exclusion, 37% of nests in exclusion plots had disappeared compared to 0% of nests in control plots. Ants' foraging success and behavior were sensitive to changes in habitat quality due to the plant successional process triggered by a restoration intervention. This study spotlights on the utility of animal foraging behavior in the evaluation of habitat restoration programs. PMID- 27252406 TI - Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography. AB - This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during the recovery phase. Monocyte cytokine responses to LPS, DC subsets and co-stimulatory molecule expression were compared with controls. Duodenal morphology and occludin expression were also assessed. Monocytes obtained before ERCP from jaundiced patients demonstrated reduced cytokine responses to endotoxin compared with controls (IL-1beta: 2678 compared with 4631 pg/ml, P=0.04 and IL-6: 3442 compared with 6157 pg/ml, P=0.002). Monocytes from patients with malignancy had poorer responses to endotoxin than from those with benign OJ (IL-1beta: 2025 compared with 3332 pg/ml, P=0.001). After ERCP, the secretion of inflammatory cytokines by monocytes obtained from jaundiced patients increased (IL-1beta: 2150 compared with 2520 pg/ml, P=0.03 and IL-6: 2488 compared with 3250 pg/ml, P=0.01). Occludin expression (85 compared with 95%, P=0.004) and mean duodenal villus height (334 compared with 404 MUm, P=0.03) were lower in jaundiced patients. Before biliary drainage, patients with OJ had a higher percentage of myeloid dendritic cells (mDCs) and greater mDC expression of CD40 (P=0.04) and CD86 (P=0.04). Monocytes from patients with OJ had lower proinflammatory cytokine secretion in response to LPS, an effect reversed following biliary drainage. PMID- 27252408 TI - Diel Rhythms in Monochamus (Coleoptera: Cerambycidae): Production of and Response to a Male-Produced Aggregation Pheromone. AB - Recent research has shown that several species in the genus Monochamus, including Monochamus scutellatus scutellatus (Say) and Monochamus notatus (Drury), a close congener, are attracted to an aggregation pheromone, monochamol, but only M. s. scutellatus produces it. Investigations were conducted to determine if there is a diel rhythm in production of monochamol or response to monochamol + host attractants in field trials by M. s. scutellatus and M. notatus to prevent cross attraction with each other. Volatiles were collected from males and females of M. s. scutellatus and M. notatus every 8 h and analyzed by coupled gas chromatography-mass spectrometry. Traps baited with monochamol and the host volatiles alpha-pinene and ethanol were checked every 8 h in field tests. Only male M. s. scutellatus produced the pheromone, and did so in similar quantities during each 8-h time interval assessed, suggesting there is no diel rhythm in pheromone production. In field tests conducted in early to mid-July, significantly more M. s. scutellatus were captured during morning hours, and significantly more M. notatus were caught during afternoon or early evening hours, suggesting temporal partitioning of flight or in their response to the pheromone lures when both species are present. A temporal switch occurred later in the seasonal flight period (mid-August) when densities of M. s. scutellatus were low; all M. notatus and only one M. s. scutellatus were caught during morning hours. This suggests a temporal separation in mate location behavior when both species are abundant and using the same host to avoid interspecific mating. PMID- 27252410 TI - Transient focal leukoencephalopathy with cerebral oedema as a presentation of cerebral amyloid angiopathy. PMID- 27252409 TI - The Thermal Breadth of Nylanderia fulva (Hymenoptera: Formicidae) Is Narrower Than That of Solenopsis invicta at Three Thermal Ramping Rates: 1.0, 0.12, and 0.06 degrees C min-1. AB - Determining the upper (CTmax) and lower (CTmin) critical thermal limits of invasive ants provides insight into how temperature could shape their distribution, seasonality, and daily activity. Understanding the potential distribution of invasive ants is imperative to improving quarantine and management efforts. Nylanderia fulva (Mayr) (tawny crazy ant) and Solenopsis invicta (Buren) (red imported fire ant) are invasive ants that are established throughout the southeastern United States. Recent studies have found that body size and thermal ramping rate can affect the estimation of critical thermal limits. However, the effects of both variables and their interactions on the thermal limits of N. fulva and S. invicta have not previously been described. Thus, we evaluated the impacts of body size and ramping rate on the critical thermal limits of N. fulva and S. invicta Overall, N. fulva had a narrower thermal breadth than S. invicta (Nf CTmin = 7.3 degrees C and Nf CTmax = 41.3 degrees C vs. Si CTmin = 4.1 degrees C and Si CTmax = 45.3 degrees C). For both species, slower ramping rates resulted in lower CTmax values and ants with smaller head capsules had a narrower thermal breadth than ants with larger head capsules. These data improve our understanding of the critical thermal limits of both species and could be useful for developing predictive models that estimate the future spread of these invasive ants in nonnative ranges. PMID- 27252411 TI - Clinicopathological case: rapid cognitive decline in an older man. PMID- 27252413 TI - Nivolumab and Pembrolizumab for Non-Small Cell Lung Cancer. AB - The outcomes for patients with previously treated advanced stage non-small lung cancer (NSCLC) are very poor, with a modest benefit from chemotherapy over best supportive care. Immunotherapy offers a novel approach for the treatment of these patients, with two anti-programmed death 1 (PD-1) checkpoint inhibitors, nivolumab and pembrolizumab, recently approved by the FDA based on large randomized clinical trials showing increased overall survival compared with standard second-line docetaxel. Although only a subset of patients benefit from these drugs, the treatment is usually well tolerated and the responses are often durable, with an unprecedented number of survivors 3 years after starting the therapy. The next steps should be the identification of reliable predictors for benefit from immunotherapy with checkpoint inhibitors and the pursuit of well designed combination therapies. In this article, we review the rationale for the use of checkpoint inhibitors in NSCLC, the data from phase I and randomized clinical trials, and future directions. Clin Cancer Res; 22(15); 3713-7. (c)2016 AACR. PMID- 27252412 TI - GTL001, A Therapeutic Vaccine for Women Infected with Human Papillomavirus 16 or 18 and Normal Cervical Cytology: Results of a Phase I Clinical Trial. AB - PURPOSE: Women infected with human papillomavirus (HPV) with normal cytology to mild abnormalities currently have no treatment options other than watchful waiting or surgery if high-grade cervical lesions or cancer develop. A therapeutic vaccine would offer the possibility of preventing high-grade lesions in HPV-infected women. GTL001 is a therapeutic vaccine composed of recombinant HPV16 and HPV18 E7 proteins fused to catalytically inactive Bordetella pertussis CyaA. This study examined the tolerability and immunogenicity of GTL001 in women infected with HPV16 or HPV18 with normal cytology. EXPERIMENTAL DESIGN: This was a phase I trial (EudraCT No. 2010-018629-21). In an open-label part, subjects received two intradermal vaccinations 6 weeks apart of 100 or 600 MUg GTL001 + topical 5% imiquimod cream at the injection site. In a double-blind part, subjects were randomized 2:1:1 to two vaccinations 6 weeks apart of 600 MUg GTL001 + imiquimod, 600 MUg GTL001 + placebo cream, or placebo + imiquimod. RESULTS: Forty-seven women were included. No dropouts, treatment-related serious adverse events, or dose-limiting toxicities occurred. Local reactions were transient and mostly mild or moderate. HPV16/18 viral load decreased the most in the 600 MUg GTL001 + imiquimod group. In post hoc analyses, the 600 MUg GTL001 + imiquimod group had the highest rates of initial and sustained HPV16/18 clearance. Imiquimod increased antigen-specific T-cell response rates but not rates of solicited reactions. All subjects seroconverted to CyaA. CONCLUSIONS: For women infected with HPV16 or HPV18 with normal cervical cytology, GTL001 was immunogenic and had acceptable safety profile. Clin Cancer Res; 22(13); 3238-48. (c)2016 AACR. PMID- 27252414 TI - Cancer Tills the Premetastatic Field: Mechanistic Basis and Clinical Implications. AB - A growing body of work has shown that cancer metastasis is not a random spontaneous event; rather, it is the culmination of a cascade of priming steps through which a subpopulation of the tumor cells acquires invasive traits while readying a permissive environment, termed the "premetastatic niche," in which distant metastases can occur. Signals from the primary tumor mobilize and adapt immune cells as well as directly communicating with distant niche cells to induce a broad spectrum of adaptations in target organs, including the induction of angiogenesis, inflammation, extracellular matrix remodeling, and metabolic reprogramming. Together, these interactions facilitate the formation of a premetastatic niche composed of a variable mix of resident and recruited immune cells, endothelial cells, and stromal cells connected through a complex signaling network that we are only beginning to understand. Here, we summarize the latest findings on how cancer induces and guides the formation of this premetastatic niche as well as potential prognostic markers and therapeutic targets that may lead to a better understanding and effective treatment of metastatic disease. Clin Cancer Res; 22(15); 3725-33. (c)2016 AACR. PMID- 27252415 TI - Image Analysis-based Assessment of PD-L1 and Tumor-Associated Immune Cells Density Supports Distinct Intratumoral Microenvironment Groups in Non-small Cell Lung Carcinoma Patients. AB - PURPOSE: We investigated the correlation between immunohistochemical PD-L1 expression and tumor-associated immune cells (TAICs) density in non-small cell lung carcinoma (NSCLC) and correlated them with clinicopathologic variables. EXPERIMENTAL DESIGN: Tumor tissue specimens from 254 stage I-III NSCLCs [146 adenocarcinomas; 108 squamous cell carcinomas (SCCs)] were examined. PD-L1 expression in malignant cells and macrophages and the density of TAICs expressing CD3, CD4, CD8, CD57, granzyme B, CD45RO, PD-1, FOXP3, and CD68 were evaluated using immunohistochemistry and image analysis. RESULTS: Malignant cells PD-L1 H score > 5 was detected in 23% of adenocarcinomas and 31% of SCCs, and no significant differences were detected comparing both histologies; the median H score in macrophages was significantly higher in SCC than in adenocarcinoma (P < 0.001). In adenocarcinoma, high malignant cells PD-L1 expression and high TAIC density correlated with solid histology, smoking history, and airflow limitation. Multivariate analysis demonstrated that high CD57-positive cell density correlated with better recurrence-free survival (RFS; P = 0.0236; HR, 0.457) and overall survival (OS; P = 0.0261; HR, 0.481) rates for SCC. High CD68-positive cell density in intratumoral compartment correlated with better RFS (P = 0.0436; HR, 0.553) for adenocarcinoma. The combination of low CD4/CD8/C68-positive cell density and PD-L1 H-score >5 in malignant cells identified small subset of adenocarcinomas with worse outcomes (RFS: P = 0.036; HR, 4.299; OS: P = 0.00034; HR, 5.632). CONCLUSIONS: We detected different PD-L1 expression and TAIC density patterns in NSCLC. Distinct groups of tumor microenvironment correlated with NSCLC clinicopathologic features, including outcome. Clin Cancer Res; 22(24); 6278-89. (c)2016 AACR. PMID- 27252416 TI - Heterogeneous Mechanisms of Primary and Acquired Resistance to Third-Generation EGFR Inhibitors. AB - PURPOSE: To identify novel mechanisms of resistance to third-generation EGFR inhibitors in patients with lung adenocarcinoma that progressed under therapy with either AZD9291 or rociletinib (CO-1686). EXPERIMENTAL DESIGN: We analyzed tumor biopsies from seven patients obtained before, during, and/or after treatment with AZD9291 or rociletinib (CO-1686). Targeted sequencing and FISH analyses were performed, and the relevance of candidate genes was functionally assessed in in vitro models. RESULTS: We found recurrent amplification of either MET or ERBB2 in tumors that were resistant or developed resistance to third generation EGFR inhibitors and show that ERBB2 and MET activation can confer resistance to these compounds. Furthermore, we identified a KRASG12S mutation in a patient with acquired resistance to AZD9291 as a potential driver of acquired resistance. Finally, we show that dual inhibition of EGFR/MEK might be a viable strategy to overcome resistance in EGFR-mutant cells expressing mutant KRAS CONCLUSIONS: Our data suggest that heterogeneous mechanisms of resistance can drive primary and acquired resistance to third-generation EGFR inhibitors and provide a rationale for potential combination strategies. Clin Cancer Res; 22(19); 4837-47. (c)2016 AACR. PMID- 27252417 TI - Cross-Stratification and Differential Risk by Breast Cancer Index and Recurrence Score in Women with Hormone Receptor-Positive Lymph Node-Negative Early-Stage Breast Cancer. AB - PURPOSE: Previous results from the TransATAC study demonstrated that both the Breast Cancer Index (BCI) and the OncotypeDX Recurrence Score (RS) added significant prognostic information to clinicopathologic factors over a 10-year period. Here, we examined cross-stratification between BCI and RS to directly compare their prognostic accuracy at the individual patient level. EXPERIMENTAL DESIGN: A total of 665 patients with hormone receptor-positive (HR+) and lymph node-negative disease were included in this retrospective analysis. BCI and RS risk groups were determined using predefined clinical cut-off points. Kaplan Meier estimates of 10-year risk of distant recurrence (DR) and log-rank tests were used to examine cross-stratification between BCI and RS. RESULTS: As previously reported, both RS and BCI were significantly prognostic in years 0 to 10. BCI provided significant additional prognostic information to the Clinical Treatment Score (CTS) plus RS (DeltaLR-chi2 = 11.09; P < 0.001), whereas no additional prognostic information was provided by RS to CTS plus BCI (DeltaLR chi2 = 2.22; P = 0.1). Restratification by BCI of the low and intermediate RS risk groups led to subgroups with significantly different DR rates (P < 0.001 and P = 0.003, respectively). In contrast, restratified subgroups created by RS of BCI risk groups did not differ significantly. CONCLUSIONS: In this retrospective analysis, BCI demonstrated increased prognostic accuracy versus RS. Notably, BCI identified subsets of RS low and RS intermediate risk patients with significant and clinically relevant rates of DR. These results indicate that additional subsets of women with HR+, lymph node-negative breast cancer identified by BCI may be suitable candidates for adjuvant chemotherapy or extended endocrine therapy. Clin Cancer Res; 22(20); 5043-8. (c)2016 AACRSee related commentary by Brufsky and Davidson, p. 4963. PMID- 27252418 TI - High CDK6 Protects Cells from Fulvestrant-Mediated Apoptosis and is a Predictor of Resistance to Fulvestrant in Estrogen Receptor-Positive Metastatic Breast Cancer. AB - PURPOSE: Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a major clinical problem. Recently, the CDK4/6 inhibitor palbociclib combined with letrozole or fulvestrant was approved for treatment of ER+ advanced breast cancer. However, the role of CDK4/6 in endocrine resistance and their potential as predictive biomarkers of endocrine treatment response remains undefined. EXPERIMENTAL DESIGN: We investigated the specific role of increased CDK6 expression in fulvestrant-resistant cells by gene knockdown and treatment with palbociclib, and evaluated the effect in cell proliferation, apoptosis, and kinase activity. Furthermore, we evaluated CDK6 expression in metastatic samples from breast cancer patients treated or not with fulvestrant. RESULTS: We found increased expression of CDK6 in two fulvestrant-resistant cell models versus sensitive cells. Reduction of CDK6 expression impaired fulvestrant resistant cell growth and induced apoptosis. Treatment with palbociclib resensitized fulvestrant-resistant cells to fulvestrant through alteration of retinoblastoma protein phosphorylation. High CDK6 levels in metastatic samples from two independent cohorts of breast cancer patients treated with fulvestrant (N = 45 and 46) correlated significantly with shorter progression-free survival (PFS) on fulvestrant treatment (P = 0.0006 and 0.018), whereas no association was observed in patients receiving other first- or second-/third-line endocrine treatments (N = 68, P = 0.135 and 0.511, respectively). CONCLUSIONS: Our results indicate that upregulation of CDK6 may be an important mechanism in overcoming fulvestrant-mediated growth inhibition in breast cancer cells. Patients with advanced ER+ breast cancer exhibiting high CDK6 expression in the metastatic lesions show shorter PFS upon fulvestrant treatment and thus may benefit from the addition of CDK4/6 inhibitors in their therapeutic regimens. Clin Cancer Res; 22(22); 5514-26. (c)2016 AACR. PMID- 27252419 TI - Rituximab in the Treatment of Jo1 Antibody-associated Antisynthetase Syndrome: Anti-Ro52 Positivity as a Marker for Severity and Treatment Response. AB - OBJECTIVE: Rituximab (RTX) has been used successfully for the treatment of severe Jo1 antibody-associated antisynthetase syndrome. The aim of this retrospective study was to evaluate the effect of RTX in severe Jo1 antisynthetase syndrome and determine predictive factors for response. METHODS: There were 61 patients with Jo1 antisynthetase syndrome identified; 18 of these received RTX. One patient was lost to followup. The remaining 17 patients and 30 out of 43 patients who were treated with conventional immunosuppressive (IS) drugs were followed for a mean of 35 months and 84 months, respectively. RESULTS: Polymyositis/dermatomyositis (95%) and interstitial lung disease (ILD; 66%) were the dominant clinical manifestations. Detection of anti-Ro52 antibodies (43%) was significantly associated with acute-onset ILD (p = 0.016) with O2 dependency, and patients with high concentrations of anti-Ro52 (20%) had the highest risk (p = 0.0005). Sixteen out of 18 patients (89%) showed a fast and marked response to RTX. Among those patients who were highly positive for anti-Ro52, response to RTX was seen in 7 out of 7 cases (100%), but no response to cyclophosphamide (n = 4), cyclosporine A (n = 3), azathioprine (n = 9), methotrexate (n = 5), or leflunomide (n = 2) was observed. One patient treated with RTX died of pneumonia. CONCLUSION: RTX is effective in the treatment of severe forms of Jo1 antisynthetase syndrome. In our retrospective study, the presence of high anti-Ro52 antibody concentrations predicts severe acute-onset ILD and nonresponse to IS drugs. In contrast to conventional IS, RTX is equally effective in patients with Jo1 antisynthetase syndrome, independent of their anti-Ro52 antibody status. PMID- 27252420 TI - Costs in Relation to Disability, Disease Activity, and Health-related Quality of Life in Rheumatoid Arthritis: Observational Data from Southern Sweden. AB - OBJECTIVE: To compare how costs relate to disability, disease activity, and health-related quality of life (HRQOL) in rheumatoid arthritis (RA). METHODS: Antitumor necrosis factor (anti-TNF)-treated patients with RA in southern Sweden (n = 2341) were monitored 2005-2010. Health Assessment Questionnaire (HAQ), 28 joint Disease Activity Score (DAS28), and EQ-5D scores were linked to register derived costs of antirheumatic drugs (excluding anti-TNF agents), patient care, and work loss from 30 days before to 30 days after each visit (n = 13,289). Associations of HAQ/DAS28/EQ-5D to healthcare (patient care and drugs) and work loss costs (patients < 65 yrs) were studied in separate regression models, comparing standardized beta coefficients by nonparametric bootstrapping to assess which measure best reflects costs. Analyses were conducted based on both individual means (linear regression, comparing between-patient associations) and by generalized estimating equations (GEE), using all observations to also account for within-patient associations of HAQ/DAS28/EQ-5D to costs. RESULTS: Regardless of the methodology (linear or GEE regression), HAQ was most closely related to both cost types, while work loss costs were also more closely associated with EQ 5D than DAS28. The results of the linear models for healthcare costs were standardized beta = 0.21 (95% CI 0.15-0.27), 0.16 (0.11-0.21), and -0.15 (-0.21 to -0.10) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D). For work loss costs, the results were standardized beta = 0.43 (95% CI 0.39 0.48), 0.27 (0.23-0.32), and -0.34 (-0.38 to -0.29) for HAQ/DAS28/EQ-5D, respectively (p < 0.05 for HAQ vs DAS28/EQ-5D and for EQ-5D vs DAS28). CONCLUSION: Overall, HAQ disability is a better marker of RA costs than DAS28 or EQ-5D HRQOL. PMID- 27252421 TI - Plasma miR-26a as a Diagnostic Biomarker Regulates Cytokine Expression in Systemic Juvenile Idiopathic Arthritis. AB - OBJECTIVE: We sought to identify specific microRNA (miRNA) for systemic juvenile idiopathic arthritis (sJIA) and to determine the involvement of these miRNA in regulating the expression of cytokines. METHODS: Microarray profiling was performed to identify differentially expressed miRNA in sJIA plasma. Levels of candidate miRNA and mRNA were assessed by real-time PCR, and cytokines were measured by ELISA. Dual-luciferase reporter assay was used to validate the direct interaction between miR-26a and interleukin 6 (IL-6). RESULTS: Forty-eight miRNA were differentially expressed in the plasma of patients with sJIA compared with healthy controls (HC). Five miRNA were selected for further validation. The expression level of miR-26a was exclusively elevated in the plasma of patients with sJIA as compared with 4 rheumatic diseases and 2 subtypes of JIA (oligoarticular and polyarticular). The levels of IL-6, IL-1beta, and tumor necrosis factor-alpha in the plasma of patients with sJIA were increased, and only IL-6 presented a positive correlation with miR-26a (r = 0.539, p < 0.0001). After stimulation with IL-6, miR-26a expression was upregulated in THP-1 cells, while the supernatant level of IL-6 was downregulated by transfection of miR-26a mimics. Consistently, direct target relationship between miR-26a and IL-6 was confirmed. CONCLUSION: This study demonstrates that miR-26a is expressed specifically and highly in sJIA plasma and suggests that miR-26a may regulate the levels of cytokines in sJIA. Our findings highlight miR-26a as a potential biomarker for the diagnosis as well as differential diagnosis of sJIA. PMID- 27252422 TI - Telomere Length and Coronary Atherosclerosis in Rheumatoid Arthritis. AB - OBJECTIVE: Telomeres protect against chromosomal end damage and shorten with each cell division; their length may be a marker of cardiovascular and overall biological aging. We examined the hypothesis that reduced telomere length is associated with increased coronary atherosclerosis in rheumatoid arthritis (RA). METHODS: We performed a cross-sectional study in 145 patients with RA and 87 control subjects frequency-matched for age, race, and sex. Coronary artery calcium score was determined by noncontrast cardiac computed tomography. Telomere length was measured from whole blood DNA, using real-time quantitative polymerase chain reaction and expressed as telomeric product to a single-copy gene product ratio (T/S ratio). Associations between telomere length, coronary artery calcium score, and 28-joint Disease Activity Score (DAS28) were assessed with Spearman correlation, proportional odds logistic regression, and linear regression, adjusting for age, race, and sex. RESULTS: Telomere length was significantly inversely correlated with age in patients with RA (rho = -0.37, p < 0.001) and control subjects (rho = -0.39, p = 0.001). Among patients with RA, for every interquartile range (IQR) decrease in telomere length (T/S ratio), the odds of higher coronary artery calcium score increased by 38% (95% CI: 4-60) after adjusting for age, race, and sex (p adjusted = 0.03). Telomere length was not associated with DAS28 (p adjusted = 0.17). Telomere length was not significantly different in patients with RA [median (IQR): 1.02 units (0.9-1.11)] compared to control subjects [1.05 units (0.95-1.17); p = 0.10]. CONCLUSION: Telomere length is inversely associated with coronary artery calcium score, independent of age, race, and sex in patients with RA. PMID- 27252423 TI - Perivascular Cells in Diffuse Cutaneous Systemic Sclerosis Overexpress Activated ADAM12 and Are Involved in Myofibroblast Transdifferentiation and Development of Fibrosis. AB - OBJECTIVE: Microvascular damage is pivotal in the pathogenesis of systemic sclerosis (SSc), preceding fibrosis, and whose trigger is not still fully understood. Perivascular progenitor cells, with profibrotic activity and function, are identified by the expression of the isoform 12 of ADAM (ADAM12) and this molecule may be upregulated by transforming growth factor-beta (TGF-beta). The goal of this work was to evaluate whether pericytes in the skin of patients with diffuse cutaneous SSc (dcSSc) expressed ADAM12, suggesting their potential contribution to the fibrotic process, and whether TGF-beta might modulate this molecule. METHODS: After ethical approval, mesenchymal stem cells (MSC) and fibroblasts (FB) were isolated from bone marrow and skin samples collected from 20 patients with dcSSc. ADAM12 expression was investigated in the skin and in isolated MSC and FB treated with TGF-beta by immunofluorescence, quantitative real-time PCR, and western blot. Further, we silenced ADAM12 expression in both dcSSc-MSC and -FB to confirm the TGF-beta modulation. RESULTS: Pericytes and FB of dcSSc skin showed an increased expression of ADAM12 when compared with healthy control skin. TGF-beta in vitro treatment induced a significant increase of ADAM12 in both SSc-MSC and -FB, with the higher levels observed in dcSSc cells. After ADAM12 silencing, the TGF-beta ability to upregulate alpha-smooth muscle actin in both SSc-MSC and SSc-FB was inhibited. CONCLUSION: Our results suggest that in SSc, pericytes that transdifferentiate toward activated FB are present in the vascular tree, and TGF-beta, while increasing ADAM12 expression, may modulate this transdifferentiation. PMID- 27252424 TI - Visual Complications in Patients with Biopsy-proven Giant Cell Arteritis: A Population-based Study. AB - OBJECTIVE: To study the clinical and laboratory characteristics of patients with biopsy-proven giant cell arteritis (GCA) with visual complications, and to evaluate the incidence rate of visual complications in GCA compared to the background population. METHODS: Data from 840 patients with GCA in the county of Skane, Sweden, diagnosed between 1997 and 2010, were used for this analysis. Cases with visual complications were identified from a diagnosis registry and confirmed by a review of medical records. The rate of visual complications in patients with GCA was compared with an age- and sex-matched reference population. RESULTS: There were 85 patients (10%) who developed >= 1 visual complication after the onset of GCA. Of the patients, 18 (21%) developed unilateral or bilateral complete visual loss. The mean age at diagnosis was 78 years (+/- 7.3); 69% were women. Compared with patients without visual complications, those with visual complication had lower C-reactive protein levels at diagnosis and were less likely to have headache, fever, and palpable abnormal temporal artery. The use of beta-adrenergic inhibitors was associated with visual complications. The incidence of visual complications among patients with GCA was 20.9/1000 person years of followup compared to 6.9/1000 person-years in the reference population, resulting in a rate ratio of 3.0 (95% CI 2.3-3.8). CONCLUSION: Ten percent of patients with GCA developed visual complications, a rate substantially higher than that of the general population. Patients with GCA who had visual complications had lower inflammatory responses and were more likely to have been treated with beta-adrenergic inhibitors compared with patients without visual complications. PMID- 27252425 TI - Comorbidities in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis versus the General Population. AB - OBJECTIVE: To evaluate the consultation rates of selected comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) compared with the general population in southern Sweden. METHODS: We used data from a population-based cohort of patients with AAV diagnosed between 1998 and 2010 in Southern Sweden (701,000 inhabitants). For each patient we identified 4 reference subjects randomly sampled from the general population and matched for year of birth, sex, area of residence, and index year. Using the population-based Skane Healthcare Register, we identified relevant diagnostic codes, registered between 1998 and 2011, for selected comorbidities assigned after the date of diagnosis of AAV or the index date for the reference subjects. We calculated rate ratios for comorbidities (AAV:reference subjects). RESULTS: There were 186 patients with AAV (95 women, mean age 64.5 yrs) and 744 reference persons included in the analysis. The highest rate ratios (AAV:reference) were obtained for osteoporosis (4.6, 95% CI 3.0-7.0), followed by venous thromboembolism (4.0, 95% CI 1.9-8.3), thyroid diseases (2.1, 95% CI 1.3-3.3), and diabetes mellitus (2.0, 95% CI 1.3-2.9). For ischemic heart disease, the rate ratio of 1.5 (95% CI 1.0-2.3) did not reach statistical significance. No statistically significant differences were found for cerebrovascular accidents. CONCLUSION: AAV is associated with increased consultation rates of several comorbidities including osteoporosis and thromboembolic and endocrine disorders. Comorbid conditions should be taken into consideration when planning and providing care for patients with AAV. PMID- 27252426 TI - The Effect of Reduced or Withdrawn Etanercept-methotrexate Therapy on Patient reported Outcomes in Patients with Early Rheumatoid Arthritis. AB - OBJECTIVE: An analysis of a clinical trial to assess the effects of treatment reduction and withdrawal on patient-reported outcomes (PRO) in patients with early, moderate to severe rheumatoid arthritis (RA) who achieved 28-joint Disease Activity Score (DAS28) low disease activity (LDA) or remission with etanercept (ETN) plus methotrexate (MTX) therapy. METHODS: During treatment induction, patients received open-label ETN 50 mg weekly plus MTX for 52 weeks. In the reduced-treatment phase, patients with DAS28-erythrocyte sedimentation rate (ESR) <= 3.2 at Week 39 and DAS28-ESR < 2.6 at Week 52 in the open-label phase were randomized to double-blind treatment with ETN 25 mg plus MTX, MTX, or placebo (PBO) for 39 weeks (weeks 0-39). In the third phase, patients who achieved DAS28 remission (DAS28-ESR < 2.6) or LDA (2.6 <= DAS28-ESR <= 3.2) at Week 39 in the double-blind phase had all treatment withdrawn and were observed for an additional 26 weeks (weeks 39-65). RESULTS: Of the 306 patients enrolled, 193 were randomized in the double-blind phase and 131 participated in the treatment withdrawal phase. After reduction or withdrawal of ETN 50 mg/MTX, patients reduced to ETN 25 mg/MTX experienced slight, nonsignificant declines in the majority of PRO measures, whereas switching to PBO or MTX alone caused significant declines. Presenteeism and activity impairment scores were significantly better in the ETN reduced-dose group versus MTX monotherapy and PBO at Week 39 (p <= 0.05). CONCLUSION: In patients with early RA who achieved remission while receiving full-dose ETN/MTX, continuing combination therapy at a lower dose did not cause a significant worsening of PRO response, but switching to MTX alone or PBO did. ClinicalTrials.gov identifier: NCT00913458. PMID- 27252427 TI - Correlates of Hip Cartilage Defects: A Cross-sectional Study in Older Adults. AB - OBJECTIVE: Knee cartilage defects are a key feature of osteoarthritis (OA) but correlates of hip defects remain unexplored. The aims of this cross-sectional study were to describe the correlates of hip cartilage defects. METHODS: The study included 194 subjects from the Tasmanian Older Adult Cohort who had right hip short-tau inversion recovery magnetic resonance imaging (MRI). Hip cartilage defects were assessed and categorized as grade 0 = no defects, grade 1 = focal blistering or irregularities on cartilage or partial thickness defect, and grade 2 = full thickness defect. Hip pain was determined by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Hip structural changes were measured on MRI, and hip radiographic OA (ROA) was assessed. Leg strength and physical activity were assessed using dynamometer and pedometers, respectively. Data were analyzed using log binomial and linear regression. RESULTS: Of 194 subjects, 24% (n = 48) had no defects, 34% (n = 66) had grade 1, and 41% (n = 80) had grade 2. In multivariable analyses, any hip defects were associated with greater hip pain [prevalence ratio (PR) 1.20, 95% CI 1.02-1.35] and lower mean leg strength (men; mean ratio 0.83, 95% CI 0.67-0.98). Grade 1 defects were associated with hip bone marrow lesions (BML; PR 1.42, 95% CI 1.03-1.96) and high cartilage signal (men; PR 1.84, 95% CI 1.27-2.70), but not with hip pain or other structural findings. Grade 2 defects were associated with greater hip pain (PR 1.40, 95% CI 1.09-1.80), hip BML (PR 1.45, 95% CI 1.15-1.85), hip effusion cross sectional area (PR 1.14, 95% CI 1.01-1.30), hip ROA (men; PR 1.60, 95% CI 1.13 2.25), and steps/day (PR 0.97, 95% CI 0.96-0.99). CONCLUSION: Grade 2 defects in both sexes and grade 1 defects (mostly in men) are associated with clinical, demographic, and structural factors relevant for OA. Damage to the hip cartilage could be one of the major causes of rapid disease progression and pathophysiology of hip defects. The topic needs further study. PMID- 27252428 TI - Predictors of Loss of Remission and Disease Flares in Patients with Axial Spondyloarthritis Receiving Antitumor Necrosis Factor Treatment: A Retrospective Study. AB - OBJECTIVE: The aim of this study was to evaluate rate and predictive factors of loss of remission and disease flare in patients with axial spondyloarthritis (axSpA) receiving antitumor necrosis factor (anti-TNF) treatment. METHODS: In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria, treated with adalimumab, etanercept, or infliximab with a minimum followup of 12 months and satisfying the ASAS partial remission criteria and/or Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were studied. Disease flare was defined as a Bath Ankylosing Spondylitis Disease Activity Index score > 4.5 or ASDAS score > 2.5 on at least 1 occasion. RESULTS: One hundred seventy-four patients with axSpA were studied. After a median [interquartile range (IQR)] followup of 4 years (2-6), 37 patients (21.2%) experienced a loss of remission and 28 (16.1% of the whole study group) a disease flare. Median (IQR) duration of remission in patients who lost this status was 1 year (0.625-2). Higher median erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, continuous nonsteroidal antiinflammatory drug (NSAID) use, and an ASDAS-CRP >= 0.8 during the remission period were significantly associated with both loss of remission and disease flare. At the multivariate analysis, continuous NSAID intake (OR 4.05, 95% CI 1.4-11.74, p = 0.010) and ESR > 15 (OR 2.90, 95% CI 1.23 6.82, p = 0.015) were the only factors predictive of disease reactivation. CONCLUSION: In this study, loss of remission and disease flares occurred, respectively, in about 21% and 16% of the patients with axSpA who achieved a state of remission while receiving anti-TNF therapy. Residual disease activity was associated with disease reactivation. PMID- 27252429 TI - Trends in Emergency Department Visits and Charges for Gout in the United States between 2006 and 2012. AB - OBJECTIVE: To examine temporal trends in the rate of gout emergency department (ED) visits and charges in the United States between 2006 and 2012. METHODS: A serial cross-sectional analysis of the Nationwide Emergency Department Sample. RESULTS: The rate of ED visits for gout in adults overall increased from 75.0 to 85.4 per 100,000 persons over the study period (14% increase, p < 0.001), and increased 29% for those aged 45-54 years. Nationwide ED charges increased from $156 million to $281 million (80% increase, p < 0.001). CONCLUSION: Between 2006 and 2012, the rate of gout ED visits increased among US adults, most notably in those aged 45-54 years. PMID- 27252430 TI - The Effect of the Presence of Fibromyalgia on Common Clinical Disease Activity Indices in Patients with Psoriatic Arthritis: A Cross-sectional Study. AB - OBJECTIVE: To study the effect of the presence of fibromyalgia (FM) on common clinical disease activity indices in patients with psoriatic arthritis (PsA). METHODS: Seventy-three consecutive outpatients with PsA (mean age 51.7 yrs; 42 females, 57.5%) were enrolled in a prospective cross-sectional study. FM was determined according to American College of Rheumatism criteria (2010 and 1990). All patients underwent clinical evaluation of disease activity and completed the Health Assessment Questionnaire (HAQ), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Dermatology Life Quality Index, and the Leeds Enthesitis Index (LEI). Disease activity was evaluated using the Composite Psoriatic Disease Activity Index (CPDAI), minimal disease activity (MDA), and the Disease Activity Index for Psoriatic Arthritis (DAPSA) scores. RESULTS: The overall prevalence of FM was 17.8% (13 patients), and all but 1 were women (12 patients, 92.3%, p = 0.005). CPDAI and DAPSA scores were significantly higher in patients with coexisting PsA and FM (9.23 +/- 1.92 and 27.53 +/- 19.23, respectively) than in patients with PsA only (4.25 +/- 3.14 and 12.82 +/- 12.71, respectively; p < 0.001 and p = 0.003). None of the patients with FM + PsA met the criteria for MDA, whereas 26 PsA-only patients did (43.3%, p = 0.003). HAQ, BASDAI, and LEI scores were significantly worse in patients with PsA and associated FM. CONCLUSION: Coexisting FM is related to worse scores on all tested measures in patients with PsA. Its influence should be taken into consideration in the treatment algorithm to avoid unnecessary upgrading of treatment. PMID- 27252431 TI - Differences in Clinical Features and Mortality between Childhood-onset and Adult onset Systemic Lupus Erythematosus: A Prospective Single-center Study. AB - OBJECTIVE: To compare clinical features and mortality between childhood-onset systemic lupus erythematosus (cSLE) and adult-onset SLE (aSLE) in a prospective single-center cohort. METHODS: A total of 1112 patients with SLE (133 cSLE and 979 aSLE) were enrolled and followed from 1998 to 2012. The 2 groups were compared regarding American College of Rheumatology (ACR) classification criteria for SLE, autoantibodies, disease activity measured by the Adjusted Mean SLE Disease Activity Index (AMS), damage measured by the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), and medication. The standardized mortality ratio (SMR) was calculated. Predictors of mortality in SLE were evaluated using Cox proportional hazard models. RESULTS: After a mean followup of 7.6 years, patients with cSLE had a higher number of cumulative ACR criteria and a higher AMS (p < 0.001 each), but there was no difference in SDI (p = 0.797). Immunosuppressants were used more frequently by patients with cSLE (p < 0.001). The SMR of cSLE was 18.8 (95% CI 8.6-35.6), significantly higher than that of aSLE (2.9, 95% CI 2.1-3.9). We found cSLE to be an independent predictor of mortality (HR 3.6, p = 0.008). Moreover, presence of hemolytic anemia (7.2, p = 0.034) and antiphospholipid antibody (aPL; 3.8, p = 0.041) increased the magnitude of risk of early mortality more in the patients with cSLE than in those with aSLE. CONCLUSION: The clinical course of cSLE as measured by number of clinical manifestations and disease activity is worse than that of aSLE. Also, cSLE patients with hemolytic anemia and aPL are at greater risk of death than patients with aSLE who have those features. PMID- 27252432 TI - Intra-Articular, Single-Shot Hylan G-F 20 Hyaluronic Acid Injection Compared with Corticosteroid in Knee Osteoarthritis: A Double-Blind, Randomized Controlled Trial. AB - BACKGROUND: The treatment of knee osteoarthritis with hyaluronic acid or corticosteroid injection has been widely used. The purpose of this study was to compare the efficacy of hyaluronic acid (hylan G-F 20) with triamcinolone acetonide as a single intra-articular injection for knee osteoarthritis. METHODS: This study was a prospective, randomized, double-blind clinical trial. Participants with symptomatic knee osteoarthritis were recruited. They were randomized to receive a single-shot, intra-articular injection of either 6 mL of hylan G-F 20 or 6 mL of a solution comprising 1 mL of 40-mg triamcinolone acetonide and 5 mL of 1% lidocaine with epinephrine. The primary outcomes were knee pain severity, knee function, and range of motion at 6 months. Ninety-nine patients were assessed before injection and underwent a 6-month follow-up. Patients and evaluators were blinded. Multilevel regression models were used to estimate differences between the groups. RESULTS: At the 6-month follow-up, compared with patients who took hylan G-F 20, patients who took triamcinolone acetonide had similar improvement in knee pain, knee function, and range of motion. The difference in mean outcome scores between groups was, with regard to knee pain, a visual analog scale (VAS) score of 3 points (95% confidence interval [95% CI], -6 to 11 points); with regard to knee function, a modified Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of 0 points (95% CI, -8 to 6 points); and, with regard to range of motion, flexion of -1 degrees (95% CI, -5 degrees to 2 degrees ) and extension of 0 degrees (95% CI, -0.5 degrees to 0.5 degrees ). However, patients who took triamcinolone acetonide had better pain improvement from 24 hours until 1 week after injection; the mean difference between groups with regard to the VAS score was 12 points (95% CI, 5 to 20 points; p = 0.002) at 24 hours and 9 points (95% CI, 1 to 15 points; p = 0.018) at 1 week. At 2 weeks after injection, patients who took triamcinolone acetonide also had better knee functional improvement; the mean difference between groups for the modified WOMAC score was 6 points (95% CI, 0.7 to 12 points; p = 0.03). Both groups had improvement in pain, knee function, and range of motion during the 6-month follow-up (p < 0.0001). CONCLUSIONS: Triamcinolone acetonide provided similar improvement in knee pain, function, and range of motion compared with hylan G-F 20 at the 6-month follow-up, with better pain control in the first week and better knee functional improvement in the second week. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 27252433 TI - Reverse Shoulder Arthroplasty for Malunions of the Proximal Part of the Humerus (Type-4 Fracture Sequelae). AB - BACKGROUND: The treatment of fracture sequelae of the proximal part of the humerus in combination with posttraumatic arthritis is challenging. The reported results of treatment with anatomic shoulder arthroplasty are disappointing. The aim of this multicenter study was to analyze the clinical and radiographic results of reverse shoulder arthroplasty for treatment of posttraumatic sequelae of the proximal part of the humerus with malunion of the tuberosities. METHODS: This was a retrospective, multicenter study of 42 patients (42 shoulders) with the diagnosis of posttraumatic sequelae of the proximal part of the humerus with malunions of the tuberosities who were treated with reverse shoulder arthroplasty between 2000 and 2010. The mean age at the time of arthroplasty was 68 years (range, 27 to 83 years; median, 70 years). The dominant side was treated in 24 cases. The mean clinical and radiographic follow-up was 4 years (range, 2 to 13 years; median, 3.5 years). The Constant score including subgroups, shoulder flexion, rotation motion, and radiographs of the affected shoulders were analyzed before the surgical procedure and at the time of the latest follow-up. Patients categorized their postoperative results as very good, good, satisfactory, or unsatisfactory. RESULTS: The mean Constant score increased from 19.7 points (range, 0 to 52 points) preoperatively to 54.9 points (range, 21 to 83 points) postoperatively (p < 0.0001). All of the subgroups of the Constant score also increased, as did active shoulder flexion and external rotation (all p < 0.0001). In one case, loosening of the humeral and glenoid components occurred. Scapular notching was present in 22 shoulders (52%) and was grade 1 in 12 cases, grade 2 in 4 cases, grade 3 in 2 cases, and grade 4 in 4 cases. Complications occurred in 4 patients (9.5%). Eighteen patients (43%) rated their result as very good, 19 (45%) rated their result as good, 4 (10%) rated their result as satisfactory, and one (2%) rated the result as unsatisfactory. CONCLUSIONS: Reverse shoulder arthroplasty is a viable treatment option for type-4 proximal humeral fracture sequelae that cannot otherwise be treated with anatomic shoulder replacement. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27252435 TI - Anatomic Hip Center Decreases Aseptic Loosening Rates After Total Hip Arthroplasty with Cement in Patients with Crowe Type-II Dysplasia: A Concise Follow-up Report at a Mean of Thirty-six Years. AB - We previously reported the two to twenty-two-year results of 145 total hip arthroplasties (THAs) with cement performed from 1969 to 1980 in 117 patients with Crowe type-II dysplasia. The purpose of the present study was to update the long-term effects of a nonanatomic hip center on component loosening and aseptic revision in this cohort. Forty-nine patients (sixty hips) were alive at a mean of thirty-six years. The overall cumulative incidence of aseptic revision at thirty five years was 32% for acetabular cups and 21% for femoral stems. Acetabular loosening was less likely with a hip center placed within the true acetabular region (TAR), <15 mm superior to the approximate femoral head center (AFHC), <35 mm superior to the interteardrop line (ITL), or within zone 1. Femoral loosening and revision were less likely with the hip center placed <35 mm superior to the ITL and within zone 1. An anatomic hip center was associated with significantly lower loosening and aseptic revision rates for both acetabular and femoral components. The current study supports the placement of acetabular components in an anatomic position to promote long-term durability after THA with cement. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27252434 TI - Safety of Osseointegrated Implants for Transfemoral Amputees: A Two-Center Prospective Cohort Study. AB - BACKGROUND: Osseointegrated implants are an alternative for prosthetic attachment for individuals unable to wear a socket following an amputation. The concept of an integrated metal implant communicating with the external environment raises substantial concern about the risk of ascending infection. We report on the safety of press-fit osseointegrated implants currently used in Australia and the Netherlands. METHODS: We prospectively recorded all adverse events in all patients with transfemoral amputation who were managed with an osseointegration implant system between 2009 and 2013 at two centers. The procedure was performed in two stages. A customized porous-coated implant was placed in the first stage, and a stoma was created in the second. Adverse events were categorized according to type (infection or "other") and severity. Infections were classified according to four grades of severity based on clinical and radiographic findings: (1) low grade soft-tissue infection, (2) high-grade soft-tissue infection, (3) bone infection, and (4) septic implant failure. RESULTS: Eighty-six patients (ninety one implants), twenty-five to eighty-one years of age, were included in the study and followed for a median of thirty-four months (range, twenty-four to seventy one months). Thirty-one patients had an uneventful course with no complications; twenty-nine developed infection (all grade 1 or 2); and twenty-six did not develop infection but had one or more other complications requiring intervention, including stoma hypergranulation (seventeen patients), soft-tissue redundancy (fourteen), proximal femoral fracture (three), inadequate osseointegration leading to implant replacement (one), implant breakage (two), and breakage of the pin used as a fail-safe mechanism (twenty-five). CONCLUSIONS: Mild infection and irritation of the soft tissue in the skin-penetration area are common in transfemoral amputees who have an osseointegrated implant. These complications were successfully managed with simple measures. Severe infections resulting in septic implant loosening are rare. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27252436 TI - A Validated Preclinical Animal Model for Primary Bone Tumor Research. AB - BACKGROUND: Despite the introduction of 21st-century surgical and neoadjuvant treatment modalities, survival of patients with osteosarcoma (OS) has not improved in two decades. Advances will depend in part on the development of clinically relevant and reliable animal models. This report describes the engineering and validation of a humanized tissue-engineered bone organ (hTEBO) for preclinical research on primary bone tumors in order to minimize false positive and false-negative results due to interspecies differences in current xenograft models. METHODS: Pelvic bone and marrow fragments were harvested from patients during reaming of the acetabulum during hip arthroplasty. HTEBOs were engineered by embedding fragments in a fibrin matrix containing bone morphogenetic protein-7 (BMP-7) and implanted into NOD-scid mice. After 10 weeks of subcutaneous growth, one group of hTEBOs was harvested to analyze the degree of humanization. A second group was injected with human luciferase-labeled OS (Luc-SAOS-2) cells. Tumor growth was followed in vivo with bioluminescence imaging. After 5 weeks, the OS tumors were harvested and analyzed. They were also compared with tumors created via intratibial injection. RESULTS: After 10 weeks of in vivo growth, a new bone organ containing human bone matrix as well as viable and functional human hematopoietic cells developed. Five weeks after injection of Luc-SAOS-2 cells into this humanized bone microenvironment, spontaneous metastatic spread to the lung was evident. Relevant prognostic markers such as vascular endothelial growth factor (VEGF) and periostin were found to be positive in OS tumors grown within the humanized microenvironment but not in tumors created in murine tibial bones. Hypoxia-inducible transcription factor-2alpha (HIF-2alpha) was detected only in the humanized OS. CONCLUSIONS: We report an in vivo model that contains human bone matrix and marrow components in one organ. BMP-7 made it possible to maintain viable mesenchymal and hematopoietic stem cells and created a bone microenvironment mimicking human physiology. CLINICAL RELEVANCE: This novel platform enables preclinical research on primary bone tumors in order to test new treatment options. PMID- 27252437 TI - Corrective Surgery for Congenital Scoliosis Associated with Split Cord Malformation: It May Be Safe to Leave Diastematomyelia Untreated in Patients with Intact or Stable Neurological Status. AB - BACKGROUND: The treatment of congenital scoliosis associated with split cord malformation (SCM) raises the issue of how to best manage such patients to avoid neurological deficit while achieving a satisfactory correction. METHODS: This prospective clinical study was performed at our center from March 2000 through June 2013. We enrolled a total of 214 patients (61 male and 153 female) with congenital scoliosis associated with SCM who were undergoing spinal correction surgery. The mean age at surgery was 14.1 years. The inclusion criteria were congenital scoliosis with confirmed SCM; status as neurologically intact or stable over the preceding 2 years; and no neurological deterioration as evidenced on traction, side-bending, or fulcrum-bending radiographs. Patients with unstable neurological status or for whom vertebral column resection surgery was planned were excluded. All patients underwent scoliosis surgery without prophylactic detethering. RESULTS: On the basis of the Pang classification, 73 patients were in the type-I SCM group, and 141 were in the type-II SCM group. The groups did not differ significantly with respect to preoperative characteristics, operative time, blood loss, or number of levels fused. The mean follow-up was 37 months (range, 24 to 108 months). The rate of scoliosis correction was lower in the type I group than in the type-II group (p < 0.05). In the type-I group, the correction rate was 48.9% at 1 week postoperatively and 42.2% at the last follow-up. In the type-II group, the correction rate was 54.7% at 1 week postoperatively and 47.9% at the last follow-up. Eleven (5.1%) of the patients experienced transient neurological complications, with no significant difference between the groups (p = 0.415). No patient experienced permanent neurological deficit during surgery or follow-up. CONCLUSIONS: Patients with congenital scoliosis associated with SCM, regardless of type, can safely and effectively undergo spinal deformity correction and achieve spinal balance without neurological intervention. For such patients with intact or stable neurological status, prophylactic detethering prior to scoliosis surgery may not be necessary. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. PMID- 27252438 TI - Biomechanical Assessment of the Anterolateral Ligament of the Knee: A Secondary Restraint in Simulated Tests of the Pivot Shift and of Anterior Stability. AB - BACKGROUND: Injury to the lateral capsular tissues of the knee may accompany rupture of the anterior cruciate ligament (ACL). A distinct lateral structure, the anterolateral ligament, has been identified, and reconstruction strategies for this tissue in combination with ACL reconstruction have been proposed. However, the biomechanical function of the anterolateral ligament is not well understood. Thus, this study had two research questions: (1) What is the contribution of the anterolateral ligament to knee stability in the ACL-sectioned knee? (2) Does the anterolateral ligament bear increased load in the absence of the ACL? METHODS: Twelve cadaveric knees from donors who were a mean (and standard deviation) of 43 +/- 15 years old at the time of death were loaded using a robotic manipulator to simulate clinical tests of the pivot shift and anterior stability. Motions were recorded with the ACL intact, with the ACL sectioned, and with both the ACL and anterolateral ligament sectioned. In situ loads borne by the ACL and anterolateral ligament in the ACL-intact knee and borne by the anterolateral ligament in the ACL-sectioned knee were determined. RESULTS: Sectioning the anterolateral ligament in the ACL-sectioned knee led to mean increases of 2 to 3 mm in anterior tibial translation in both anterior stability and simulated pivot-shift tests. In the ACL-intact knee, the load borne by the anterolateral ligament was a mean of <=10.2 N in response to anterior loads and <17 N in response to the simulated pivot shift. In the ACL-sectioned knee, the load borne by the anterolateral ligament increased on average to <55% of the load normally borne by the ACL in the intact knee. However, in the ACL-sectioned knee, the anterolateral ligament engaged only after the tibia translated beyond the physiologic limits of motion of the ACL-intact knee. CONCLUSIONS: The anterolateral ligament is a secondary stabilizer compared with the ACL for the simulated Lachman, anterior drawer, and pivot shift examinations. CLINICAL RELEVANCE: Since the anterolateral ligament engages only during pathologic ranges of tibial translation, there is a limited need for anatomical reconstruction of the anterolateral ligament in a well-functioning ACL-reconstructed knee. PMID- 27252439 TI - Posterior Fixation of APC-2 Pelvic Ring Injuries Decreases Rates of Anterior Plate Failure and Malunion. AB - BACKGROUND: Biomechanical studies suggest that augmenting anterior fixation of the pelvic ring with posterior fixation increases stability. Prior clinical studies have assessed radiographic outcomes following plate fixation of the symphysis. However, to our knowledge, none have directly compared the radiographic and clinical outcomes of anterior plate fixation alone with the outcomes of such plate fixation with the addition of posterior percutaneous screw fixation in the treatment of a partially disrupted hemipelvis. We attempted to determine whether use of an anterior symphyseal plate alone is adequate to control sagittal and coronal plane rotation and prevent malunion of an anteroposterior compression type-2 (APC-2) pelvic ring injury. METHODS: The records of all skeletally mature patients with a traumatic pelvic disruption treated from 2004 to 2014 with an anterior symphyseal plate with or without a posterior iliosacral screw were retrospectively reviewed. Patients with an APC-2 pelvic ring injury evidenced by computed tomography (CT) were included in the study and divided into 2 groups: (1) fixation of the symphysis with an anterior 3.5-mm 6-hole plate alone and (2) the same anterior fixation supplemented posteriorly with a percutaneous partially threaded 7.0 or 7.3-mm iliosacral screw. Postoperative CT scans were reviewed to assess the reduction of the pelvic ring and the position of all implants. The patients were followed for a minimum of 6 months or until the fixation failed. Examined data included demographic factors, type of and time to fixation failure, and presence of malunion. Univariate and multivariate statistical analyses were completed. RESULTS: One hundred and thirty-four patients met the inclusion criteria. Ninety-two (69%) underwent combined anterior and posterior fixation, and 42 (31%) had anterior fixation alone. The average age and duration of follow-up were 38 years and 7.2 months, respectively. Anterior plate fixation failed in 5 patients (5%) in the combined-fixation group and in 17 patients (40%) in the anterior-only group (p < 0.0001). Malunion was identified in 1 patient (1%) in the combined group and in 15 (36%) in the anterior-only cohort (p < 0.0001). CONCLUSIONS: Our study indicated that use of an anterior plate and a supplemental posterior screw for fixation of APC-2 pelvic ring injuries significantly decreases the rate of anterior plate failure and malunion compared with use of an anterior plate alone. The potential for selection and detection bias introduced by our study design limited the strength of this conclusion. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27252440 TI - Acetabular Remodeling and Role of Osteotomy After Closed Reduction of Developmental Dysplasia of the Hip. AB - BACKGROUND: The purposes of this study were to evaluate acetabular remodeling after closed reduction of developmental dysplasia of the hip (DDH) and to delineate the role of osteotomy. METHODS: Eighty-four hips with DDH treated with closed reduction and followed until the patient was 8 years of age or older were included in this study. The mean age at closed reduction was 14.0 months (range, 3 to 30 months) and that at the latest follow-up visit was 12.7 years (range, 8.0 to 24.7 years). Osteotomy was performed in 26 hips (31%) during the follow-up period, at an average age of 2.8 years (range, 2.0 to 5.8 years). The acetabular index (AI) and center-edge angle (CEA) were measured, and osteonecrosis was graded. The treatment outcome was evaluated as satisfactory (Severin grade I or II) or unsatisfactory (III or IV). We retrospectively analyzed the associations among radiographic parameters, performance of osteotomy, grade of osteonecrosis, and final outcome. RESULTS: A satisfactory outcome was observed in 67 (80%) of the 84 hips. An osteotomy was not performed in 30 of 34 hips with an AI of <32 degrees and a CEA of >14 degrees at the age of 3 years, and 28 (93%) of these 30 hips showed a satisfactory outcome. Of the 33 hips with an AI of >=32 degrees and a CEA of <=14 degrees at the age of 3 years, the 20 that had undergone an osteotomy showed a higher proportion of satisfactory outcomes than the 13 hips that had not (p = 0.01). Three of the 4 hips that showed an unsatisfactory outcome following an osteotomy had an AI of >=34 degrees at 1 year post osteotomy. Grade-II, III, or IV osteonecrosis, according to the Bucholz-Ogden classification, developed in 10 of the 84 hips, and these 10 hips had a higher proportion of unsatisfactory outcomes than did those that developed no or grade-I osteonecrosis (p = 0.004). CONCLUSIONS: Hips with DDH showing poor acetabular remodeling after closed reduction may benefit from osteotomy. The AI and CEA at the age of 3 years can serve as one of the guidelines for osteotomy. Continued surveillance for acetabular remodeling is required even after osteotomy. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 27252441 TI - Glenoid Dysplasia: Pathophysiology, Diagnosis, and Management. AB - ?Subtle forms of glenoid dysplasia may be more common than previously thought and likely predispose some patients to symptomatic posterior shoulder instability. Severe glenoid dysplasia is a rare condition with characteristic radiographic findings involving the posteroinferior aspect of the glenoid that often remains asymptomatic.?Instability symptoms related to glenoid dysplasia may develop over time with increased activities or trauma. Physical therapy focusing on rotator cuff strengthening and proprioceptive control should be the initial management.?Magnetic resonance imaging and computed tomographic arthrograms are useful for detecting subtle glenoid dysplasia by revealing the presence of an abnormally thickened or hypertrophic posterior part of the labrum, increased capsular volume, glenoid retroversion, and posteroinferior glenoid deficiency.?Open and arthroscopic labral repair and capsulorrhaphy procedures have been described for symptomatic posterior shoulder instability. Glenoid retroversion of >10 degrees may be a risk factor for failure following soft tissue-only procedures for symptomatic glenoid dysplasia.?Osseous procedures are categorized as either glenoid reorientation (osteotomy) or glenoid augmentation (bone graft), and no predictable results have been demonstrated for any surgical strategy. Glenoid osteotomies have been described for increased retroversion, with successful results, although others have noted substantial complications and poor outcomes.?In severe glenoid dysplasia, the combination of bone deficiency and retroversion makes glenoid osteotomy extremely challenging. Bone grafts placed in a lateralized position to create a blocking effect may increase the risk of the development of arthritis, while newer techniques that place the graft in a congruent position may decrease this risk. PMID- 27252442 TI - Alternative Reimbursement Models: Bundled Payment and Beyond: AOA Critical Issues. AB - The Bundled Payments for Care Improvement (BPCI) initiative was begun in January 2013 by the U.S. Centers for Medicare & Medicaid Services (CMS) through its Innovation Center authority, which was created by the U.S. Patient Protection and Affordable Care Act (PPACA). The BPCI program seeks to improve health-care delivery and to ultimately reduce costs by allowing providers to enter into prenegotiated payment arrangements that include financial and performance accountability for a clinical episode in which a risk-and-reward calculus must be determined. BPCI is a contemporary 3-year experiment designed to test the applicability of episode-based payment models as a viable strategy to transform the CMS payment methodology while improving health outcomes. A summary of the 4 models being evaluated in the BPCI initiative is presented in addition to the awardee types and the number of awardees in each model. Data from one of the BPCI designated pilot sites demonstrate that strategies do exist for successful implementation of an alternative payment model by keeping patients first while simultaneously improving coordination, alignment of care, and quality and reducing cost. Providers will need to embrace change and their areas of opportunity to gain a competitive advantage. Health-care providers, including orthopaedic surgeons, health-care professionals at post-acute care institutions, and product suppliers, all have a role in determining the strategies for success. Open dialogue between CMS and awardees should be encouraged to arrive at a solution that provides opportunity for gainsharing, as this program continues to gain traction and to evolve. PMID- 27252443 TI - Musculoskeletal Workforce Needs: Are Physician Assistants and Nurse Practitioners the Solution? AOA Critical Issues. AB - Growth estimates and demographic shifts of the population of the United States foreshadow a future heightened demand for musculoskeletal care. Although many articles have discussed this growing demand on the musculoskeletal workforce, few address the inevitable need for more musculoskeletal care providers. As we are unable to increase the number of orthopaedic surgeons because of restrictions on graduate medical education slots, physician assistants (PAs) and nurse practitioners (NPs) represent one potential solution to the impending musculoskeletal care supply shortage. This American Orthopaedic Association (AOA) symposium report investigates models for advanced practice provider integration, considers key issues affecting PAs and NPs, and proposes guidelines to help to assess the logistical and educational possibilities of further incorporating NPs and PAs into the orthopaedic workforce in order to address future musculoskeletal care needs. PMID- 27252444 TI - Utilizing Health-Care Resources Wisely: Understanding the Efficacy of Our Interventions: Commentary on an article by Nattapol Tammachote, MD, MSc, et al.: "Intra-Articular, Single-Shot Hylan G-F 20 Hyaluronic Acid Injection Compared with Corticosteroid in Knee Osteoarthritis. A Double-Blind, Randomized Controlled Trial". PMID- 27252445 TI - One Step Forward, But a Need for Caution: Commentary on an article by Munjed Al Muderis, MB ChB, FRACS, FAOrthA, et al.: "Safety of Osseointegrated Implants for Transfemoral Amputees. A Two-Center Prospective Cohort Study". PMID- 27252446 TI - MicroRNA in alcoholic hepatitis: implications for pathophysiology and treatment. PMID- 27252447 TI - Anti-inflammatory treatment of acute coronary syndromes: the need for precision medicine. PMID- 27252448 TI - Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic immuno-mediated disease primarily affecting the joints, characterized by persistent high-grade systemic inflammation. Cardiovascular morbidity and mortality are significantly increased in RA, with >50% of premature deaths attributable to cardiovascular disease. In particular, RA patients were twice as likely to experience sudden cardiac death compared with non-RA subjects, pointing to an increased propensity to develop malignant ventricular arrhythmias. Indeed, ventricular repolarization (QT interval) abnormalities and cardiovascular autonomic nervous system dysfunction, representing two well-recognized risk factors for life-threatening ventricular arrhythmias in the general population, are commonly observed in RA. Moreover, large population-based studies seem to indicate that also the prevalence of atrial fibrillation is significantly higher in RA subjects than in the general population, thus suggesting that these patients are characterized by an abnormal diffuse myocardial electrical instability. Although the underlying mechanisms accounting for the pro-arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by chronic systemic inflammatory activation, able to promote arrhythmias both indirectly, by accelerating the development of ischaemic heart disease and congestive heart failure, and directly, by affecting cardiac electrophysiology. In this integrated mechanistic view, lowering the inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk in these patients. Intriguingly, these considerations could be more generally applicable to all the diseases characterized by chronic systemic inflammation, and could help elucidate the link between low-grade chronic inflammation and arrhythmic risk in the general population. PMID- 27252449 TI - Prelude to Takotsubo cardiomyopathy: subclinical progression of antecedent myocardial ischaemia prior to symptom onset. PMID- 27252450 TI - Positive emotions and Takotsubo syndrome: 'happy heart' or 'Diagoras' syndrome? PMID- 27252452 TI - Antithrombotic therapy in heart failure patients with and without atrial fibrillation: update and future challenges. AB - Atrial fibrillation (AF) and heart failure (HF) often coexist, and patients with AF and HF have a higher risk of thromboembolic events and overall mortality compared with those with AF without HF. Additionally, the prevalence of AF increases with the severity of HF. The use of vitamin K antagonists is more unstable in patients with concomitant AF and HF, which is an independent risk factor for reduced time under therapeutic range. More recently, non-vitamin K antagonists oral anticoagulants (NOACs) have emerged as therapeutic alternatives for stroke prevention in patients with non-valvular AF, as they have been shown to be at least as efficacious and safe, with less intracranial bleeding events, compared with vitamin K antagonists. The subgroup analyses of the NOAC trials in patients with AF and HF show that the efficacy and safety of these agents are likely to be similar to those observed in patients with AF and no HF. However, many gaps in evidence exist, since HF has not been consistently defined nor used as an endpoint in these trials. In patients with HF and sinus rhythm, the risk of stroke and other thrombotic events is high, and the use of warfarin has not, to date, been shown to confer outcome benefit. The benefit of the NOAC, rivaroxaban, is being investigated in HF without AF in the ongoing COMMANDER-HF trial. This review aims to provide an insightful perspective on the use of antithrombotic treatments in patients with both AF and HF, and in patients with HF and sinus rhythm, with particular attention to the NOACs, and provides background for therapeutic, outcome and trial improvement. PMID- 27252451 TI - Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease: a 5-year multicentre prospective registry analysis. AB - Aims: Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. Methods and results: The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P< 0.001). Conclusions: Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone. PMID- 27252453 TI - Evolutionary escalation: the bat-moth arms race. AB - Echolocation in bats and high-frequency hearing in their insect prey make bats and insects an ideal system for studying the sensory ecology and neuroethology of predator-prey interactions. Here, we review the evolutionary history of bats and eared insects, focusing on the insect order Lepidoptera, and consider the evidence for antipredator adaptations and predator counter-adaptations. Ears evolved in a remarkable number of body locations across insects, with the original selection pressure for ears differing between groups. Although cause and effect are difficult to determine, correlations between hearing and life history strategies in moths provide evidence for how these two variables influence each other. We consider life history variables such as size, sex, circadian and seasonal activity patterns, geographic range and the composition of sympatric bat communities. We also review hypotheses on the neural basis for anti-predator behaviours (such as evasive flight and sound production) in moths. It is assumed that these prey adaptations would select for counter-adaptations in predatory bats. We suggest two levels of support for classifying bat traits as counter adaptations: traits that allow bats to eat more eared prey than expected based on their availability in the environment provide a low level of support for counter adaptations, whereas traits that have no other plausible explanation for their origination and maintenance than capturing defended prey constitute a high level of support. Specific predator counter-adaptations include calling at frequencies outside the sensitivity range of most eared prey, changing the pattern and frequency of echolocation calls during prey pursuit, and quiet, or 'stealth', echolocation. PMID- 27252454 TI - Energetic cost determines voluntary movement speed only in familiar environments. AB - Locomotor performance is closely related to fitness. However, in many ecological contexts, animals do not move at their maximal locomotor capacity, but adopt a voluntary speed that is lower than maximal. It is important to understand the mechanisms that underlie voluntary speed, because these determine movement patterns of animals across natural environments. We show that voluntary speed is a stable trait in zebrafish (Danio rerio), but there were pronounced differences between individuals in maximal sustained speed, voluntary speed and metabolic cost of locomotion. We accept the hypothesis that voluntary speed scales positively with maximal sustained swimming performance (Ucrit), but only in unfamiliar environments (1st minute in an open-field arena versus 10th minute) at high temperature (30 degrees C). There was no significant effect of metabolic scope on Ucrit Contrary to expectation, we rejected the hypothesis that voluntary speed decreases with increasing metabolic cost of movement, except in familiar spatial (after 10 min of exploration) and thermal (24 degrees C but not 18 or 30 degrees C) environments. The implications of these data are that the energetic costs of exploration and dispersal in novel environments are higher than those for movement within familiar home ranges. PMID- 27252455 TI - Intermittent hypoxia leads to functional reorganization of mitochondria and affects cellular bioenergetics in marine molluscs. AB - Fluctuations in oxygen (O2) concentrations represent a major challenge to aerobic organisms and can be extremely damaging to their mitochondria. Marine intertidal molluscs are well-adapted to frequent O2 fluctuations, yet it remains unknown how their mitochondrial functions are regulated to sustain energy metabolism and prevent cellular damage during hypoxia and reoxygenation (H/R). We used metabolic control analysis to investigate the mechanisms of mitochondrial responses to H/R stress (18 h at <0.1% O2 followed by 1 h of reoxygenation) using hypoxia-tolerant intertidal clams Mercenaria mercenaria and hypoxia-sensitive subtidal scallops Argopecten irradians as models. We also assessed H/R-induced changes in cellular energy balance, oxidative damage and unfolded protein response to determine the potential links between mitochondrial dysfunction and cellular injury. Mitochondrial responses to H/R in scallops strongly resembled those in other hypoxia-sensitive organisms. Exposure to hypoxia followed by reoxygenation led to a strong decrease in the substrate oxidation (SOX) and phosphorylation (PHOS) capacities as well as partial depolarization of mitochondria of scallops. Elevated mRNA expression of a reactive oxygen species-sensitive enzyme aconitase and Lon protease (responsible for degradation of oxidized mitochondrial proteins) during H/R stress was consistent with elevated levels of oxidative stress in mitochondria of scallops. In hypoxia-tolerant clams, mitochondrial SOX capacity was enhanced during hypoxia and continued rising during the first hour of reoxygenation. In both species, the mitochondrial PHOS capacity was suppressed during hypoxia, likely to prevent ATP wastage by the reverse action of FO,F1 ATPase. The PHOS capacity recovered after 1 h of reoxygenation in clams but not in scallops. Compared with scallops, clams showed a greater suppression of energy consuming processes (such as protein turnover and ion transport) during hypoxia, indicated by inactivation of the translation initiation factor EIF-2alpha, suppression of 26S proteasome activity and a dramatic decrease in the activity of Na(+)/K(+)-ATPase. The steady-state levels of adenylates were preserved during H/R exposure and AMP-dependent protein kinase was not activated in either species, indicating that the H/R exposure did not lead to severe energy deficiency. Taken together, our findings suggest that mitochondrial reorganizations sustaining high oxidative phosphorylation flux during recovery, combined with the ability to suppress ATP-demanding cellular functions during hypoxia, may contribute to high resilience of clams to H/R stress and help maintain energy homeostasis during frequent H/R cycles in the intertidal zone. PMID- 27252456 TI - Effects of high temperatures on threatened estuarine fishes during periods of extreme drought. AB - Climate change and associated increases in water temperatures may impact physiological performance in ectotherms and exacerbate endangered species declines. We used an integrative approach to assess the impact of elevated water temperature on two fishes of immediate conservation concern in a large estuary system, the threatened longfin smelt (Spirinchus thaleichthys) and endangered delta smelt (Hypomesus transpacificus). Abundances have reached record lows in California, USA, and these populations are at imminent risk of extirpation. California is currently impacted by a severe drought, resulting in high water temperatures, conditions that will become more common as a result of climate change. We exposed fish to environmentally relevant temperatures (14 degrees C and 20 degrees C) and used RNA sequencing to examine the transcriptome-wide responses to elevated water temperature in both species. Consistent with having a lower temperature tolerance, longfin smelt exhibited a pronounced cellular stress response, with an upregulation of heat shock proteins, after exposure to 20 degrees C that was not observed in delta smelt. We detected an increase in metabolic rate in delta smelt at 20 degrees C and increased expression of genes involved in metabolic processes and protein synthesis, patterns not observed in longfin smelt. Through examination of responses across multiple levels of biological organization, and by linking these responses to habitat distributions in the wild, we demonstrate that longfin smelt may be more susceptible than delta smelt to increases in temperatures, and they have little room to tolerate future warming in California. Understanding the species-specific physiological responses of sensitive species to environmental stressors is crucial for conservation efforts and managing aquatic systems globally. PMID- 27252457 TI - Developmental changes of cognitive vocal control in monkeys. AB - The evolutionary origins of human language are obscured by the scarcity of essential linguistic characteristics in non-human primate communication systems. Volitional control of vocal utterances is one such indispensable feature of language. We investigated the ability of two monkeys to volitionally utter species-specific calls over many years. Both monkeys reliably vocalized on command during juvenile periods, but discontinued this controlled vocal behavior in adulthood. This emerging disability was confined to volitional vocal production, as the monkeys continued to vocalize spontaneously. In addition, they continued to use hand movements as instructed responses during adulthood. This greater vocal flexibility of monkeys early in ontogeny supports the neoteny hypothesis in human evolution. This suggests that linguistic capabilities were enabled via an expansion of the juvenile period during the development of humans. PMID- 27252458 TI - Antimicrobial Susceptibility Patterns of Brachyspira Species Isolated from Swine Herds in the United States. AB - Outbreaks of swine dysentery, caused by Brachyspira hyodysenteriae and the recently discovered "Brachyspira hampsonii," have reoccurred in North American swine herds since the late 2000s. Additionally, multiple Brachyspira species have been increasingly isolated by North American diagnostic laboratories. In Europe, the reliance on antimicrobial therapy for control of swine dysentery has been followed by reports of antimicrobial resistance over time. The objectives of our study were to determine the antimicrobial susceptibility trends of four Brachyspira species originating from U.S. swine herds and to investigate their associations with the bacterial species, genotypes, and epidemiological origins of the isolates. We evaluated the susceptibility of B. hyodysenteriae, B. hampsonii, Brachyspira pilosicoli, and Brachyspira murdochii to tiamulin, valnemulin, doxycycline, lincomycin, and tylosin by broth microdilution and that to carbadox by agar dilution. In general, Brachyspira species showed high susceptibility to tiamulin, valnemulin, and carbadox, heterogeneous susceptibility to doxycycline, and low susceptibility to lincomycin and tylosin. A trend of decreasing antimicrobial susceptibility by species was observed (B. hampsonii > B. hyodysenteriae > B. murdochii > B. pilosicoli). In general, Brachyspira isolates from the United States were more susceptible to these antimicrobials than were isolates from other countries. Decreased antimicrobial susceptibility was associated with the genotype, stage of production, and production system from which the isolate originated, which highlights the roles of biosecurity and husbandry in disease prevention and control. Finally, this study also highlights the urgent need for Clinical and Laboratory Standards Institute-approved clinical breakpoints for Brachyspira species, to facilitate informed therapeutic and control strategies. PMID- 27252459 TI - Evaluation of the Whole-Blood Alere Q NAT Point-of-Care RNA Assay for HIV-1 Viral Load Monitoring in a Primary Health Care Setting in Mozambique. AB - Viral load testing is the WHO-recommended monitoring assay for patients on HIV antiretroviral therapy (ART). Point-of-care (POC) assays may help improve access to viral load testing in resource-limited settings. We compared the performance of the Alere Q NAT POC viral load technology (Alere Technologies, Jena, Germany), measuring total HIV RNA using finger prick capillary whole-blood samples collected in a periurban health center, with that of a laboratory-based plasma RNA test (Roche Cobas Ampliprep/Cobas TaqMan v2) conducted on matched venous blood samples. The whole-blood Alere Q NAT POC assay produced results with a bias of 0.8593 log copy/ml compared to the laboratory-based plasma assay. However, at above 10,000 copies/ml, the bias was 0.07 log copy/ml. Using the WHO-recommended threshold to determine ART failure of 1,000 copies/ml, the sensitivity and specificity of the whole-blood Alere Q NAT POC assay were 96.83% and 47.80%, respectively. A cutoff of 10,000 copies/ml of whole blood with the Alere Q NAT POC assay appears to be a better predictor of ART failure threshold (1,000 copies/ml of plasma), with a sensitivity of 84.0% and specificity of 90.3%. The precision of the whole-blood Alere Q NAT POC assay was comparable to that observed with the laboratory technology (5.4% versus 7.5%) between detectable paired samples. HIV POC viral load testing is feasible at the primary health care level. Further research on the value of whole-blood viral load to monitor antiretroviral therapy is warranted. PMID- 27252460 TI - Performance of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Aspergillus, Scedosporium, and Fusarium spp. in the Australian Clinical Setting. AB - We developed an Australian database for the identification of Aspergillus, Scedosporium, and Fusarium species (n = 28) by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). In a challenge against 117 isolates, species identification significantly improved when the in house-built database was combined with the Bruker Filamentous Fungi Library compared with that for the Bruker library alone (Aspergillus, 93% versus 69%; Fusarium, 84% versus 42%; and Scedosporium, 94% versus 18%, respectively). PMID- 27252461 TI - Identification and Antifungal Susceptibility Profile of Candida guilliermondii and Candida fermentati from a Multicenter Study in China. AB - With molecular sequencing as a gold standard, the Vitek MS, Bruker Biotyper MS, and Vitek-2 Compact systems correctly identified 92.7%, 97.0%, and 15.2% of 164 Candida guillermondii isolates, respectively, and none of 8 C. fermentati isolates. All of the isolates showed high susceptibility to echinocandins, but some C. guilliermondii isolates showed low azole susceptibility. PMID- 27252462 TI - Prosthetic Vascular Graft Infections: Bacterial Cultures from Negative-Pressure Wound-Therapy Foams Do Not Improve Diagnostics. AB - We analyzed the diagnostic value of microorganisms cultured from negative pressure-wound-therapy (NPWT) foam samples compared to that of microorganisms cultured from deep tissue samples from patients with vascular graft infections. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 58%, 86%, 81%, and 66%, respectively. The diagnostic value of microbiological cultures from NPWT foams was poor. PMID- 27252464 TI - PCR-Based Serotyping of Streptococcus pneumoniae from Culture-Negative Specimens: Novel Primers for Detection of Serotypes within Serogroup 18. AB - Six multiplex-compatible PCR primers were designed to distinguish Streptococcus pneumoniae serotypes within serogroup 18 from culturable/nonculturable pneumococcal specimens, with no cross-reactivity with other serotypes and respiratory organisms. These primers will aid in the generation of better data on vaccine/nonvaccine serotypes in invasive and carriage pneumococcal surveillance and contribute to future vaccine formulation and impact studies. PMID- 27252463 TI - Novel Method Based on Real-Time Cell Analysis for Drug Susceptibility Testing of Herpes Simplex Virus and Human Cytomegalovirus. AB - The plaque reduction assay (PRA) is the gold standard phenotypic method to determine herpes simplex virus (HSV) and human cytomegalovirus (HCMV) susceptibilities to antiviral drugs. However, this assay is subjective and labor intensive. Here, we describe a novel antiviral phenotypic method based on real time cell analysis (RTCA) that measures electronic impedance over time. The effective drug concentrations that reduced by 50% (EC50s) the cytopathic effects induced by HSV-1 and HCMV were evaluated by both methods. The EC50s of acyclovir and foscarnet against a reference wild-type (WT) HSV-1 strain in Vero cells were, respectively, 0.5 MUM and 32.6 MUM by PRA and 0.8 MUM and 93.6 MUM by RTCA. The EC50 ratios for acyclovir against several HSV-1 thymidine kinase (TK) mutants were 101.8*, 73.4*, 28.8*, and 35.4* (PRA) and 18.0*, 52.0*, 5.5*, and 87.8* (RTCA) compared to those for the WT. The EC50 ratios for acyclovir and foscarnet against the HSV-1 TK/DNA polymerase mutant were 182.8* and 9.7* (PRA) and >125.0* and 10.8* (RTCA) compared to the WT. The EC50s of ganciclovir and foscarnet against WT HCMV strain AD169 in fibroblasts were, respectively, 1.6 MUM and 27.8 MUM by PRA and 5.0 MUM and 111.4 MUM by RTCA. The EC50 ratios of ganciclovir against the HCMV UL97 mutant were 3.8* (PRA) and 8.2* (RTCA) compared to those for the WT. The EC50 ratios of ganciclovir and foscarnet against the HCMV UL97/DNA polymerase mutant were 17.1* and 12.1* (PRA) and 14.7* and 4.6* (RTCA) compared to those for the WT. RTCA allows objective drug susceptibility testing of HSV and HCMV and could permit high-throughput screening of new antivirals. PMID- 27252466 TI - QuantiFERON-TB Gold Assay on Plasma for Confirmation of Presumed Tuberculosis Related Uveitis. AB - The QuantiFERON-TB Gold assay was used to measure interferon gamma levels in plasma from 4 patients with presumed tuberculosis-related uveitis before, during, and after antitubercular therapy. After treatment, all patients showed clinical improvement. The concentrations showed a reversion to an absence of interferon gamma in one case, decreased in two cases, and remained stable in one case. These results suggest that the QuantiFERON assay may be useful for tuberculosis-related uveitis diagnosis and follow-up. PMID- 27252465 TI - Phylogenetic Analysis of Enteroaggregative Escherichia coli (EAEC) Isolates from Japan Reveals Emergence of CTX-M-14-Producing EAEC O25:H4 Clones Related to Sequence Type 131. AB - Enteroaggregative Escherichia coli (EAEC) causes acute or persistent diarrhea. The aggR gene is widely used as a marker for typical EAEC. The heterogeneity of EAEC is well known; however, there are few reports on the phylogenetic relationships of EAEC. Recently, CTX-M extended-spectrum beta-lactamase (ESBL) producing EAEC strains have been reported worldwide. To characterize EAEC strains in Japan, we investigated the population structure of EAEC. A total of 167 aggR positive strains isolated from stool specimens from diarrheal patients in Kagoshima (139 strains) and Osaka (28 strains), Japan, between 1992 and 2010 were examined for the prevalence of EAEC virulence markers, the blaCTX-M gene, and the capacity to form biofilms. Multilocus sequence typing was also conducted. EAEC strains were widely distributed across four major E. coli phylogroups. Strains of O111:H21/clonal group 40 (CG40) (30 strains), O126:H27/CG200 (13 strains), and O86a:H27/CG3570 (11 strains) in phylogroup B1 are the historical EAEC clones in Japan, and they exhibited strong biofilm formation. Twenty-nine strains of EAEC O25:H4/CG131 were identified in phylogroup B2, 79% of which produced CTX-M-14. This clone has emerged since 2003. The clone harbored plasmid-encoded EAEC virulence genes but not chromosomal virulence genes and had lower biofilm-forming capacity than historical EAEC strains. This clone most likely emerged from a pandemic uropathogenic O25:H4/sequence type 131 clone by acquiring an EAEC virulence plasmid from canonical EAEC. Surveillance of the horizontal transfer of both virulence and ESBL genes among E. coli strains is important for preventing a worldwide increase in antimicrobial drug resistance. PMID- 27252467 TI - Biofortification of rice with the essential amino acid lysine: molecular characterization, nutritional evaluation, and field performance. AB - Rice (Oryza sativa L.), a major staple crop worldwide, has limited levels of the essential amino acid lysine. We previously produced engineered rice with increased lysine content by expressing bacterial aspartate kinase and dihydrodipicolinate synthase and inhibiting rice lysine ketoglutarate reductase/saccharopine dehydrogenase activity. However, the grain quality, field performance, and integration patterns of the transgenes in these lysine-enriched lines remain unclear. In the present study, we selected several elite transgenic lines with endosperm-specific or constitutive regulation of the above key enzymes but lacking the selectable marker gene. All target transgenes were integrated into the intragenic region in the rice genome. Two pyramid transgenic lines (High Free Lysine; HFL1 and HFL2) with free lysine levels in seeds up to 25-fold that of wild type were obtained via a combination of the above two transgenic events. We observed a dramatic increase in total free amino acids and a slight increase in total protein content in both pyramid lines. Moreover, the general physicochemical properties were improved in pyramid transgenic rice, but the starch composition was not affected. Field trials indicated that the growth of HFL transgenic rice was normal, except for a slight difference in plant height and grain colour. Taken together, these findings will be useful for the potential commercialization of high-lysine transgenic rice. PMID- 27252468 TI - SLG controls grain size and leaf angle by modulating brassinosteroid homeostasis in rice. AB - Grain size and leaf angle are two important traits determining grain yield in rice. However, the mechanisms regulating the two traits remain largely unknown. Here, we characterized a rice gain-of-function mutant, slender grain Dominant (slg-D), which exhibited longer and narrower grains and larger leaf angles, similar to plants with elevated brassinosteroid (BR) levels or strengthened BR signaling. The increased cell length is responsible for the mutant phenotypes in slg-D We demonstrated that the phenotype of slg-D is caused by enhanced expression of SLG, a BAHD acyltransferase-like protein gene. SLG is preferentially expressed in young panicles and lamina joints, implying its role in controlling cell growth in those two tissues. slg-D was restored to wild type by treatment with brassinazole, an inhibitor of BR biosynthesis. Overexpression of SLG in d11-2 (deficient in BR synthesis) and d61-1 (deficient in BR signaling) did not change the existing phenotypes. The slg-D plants had elevated BR contents and, accordingly, expression of BR-related genes was changed in a manner similar to BR treatment. Moreover, SLG RNAi plants displayed mild BR-deficient phenotypes including shorter grains, smaller leaf angles, and compact semi-dwarf plant types. The in vitro biochemical assays and transgenic approaches collectively demonstrated that SLG functions as homomers. Taken together, we conclude that SLG is an important regulator in BR homeostasis and that manipulation of SLG expression to an optimal level may provide a way to develop an ideal plant type. PMID- 27252469 TI - Homologs of SCAR/WAVE complex components are required for epidermal cell morphogenesis in rice. AB - Filamentous actins (F-actins) play a vital role in epidermal cell morphogenesis. However, a limited number of studies have examined actin-dependent leaf epidermal cell morphogenesis events in rice. In this study, two recessive mutants were isolated: less pronounced lobe epidermal cell2-1 (lpl2-1) and lpl3-1, whose leaf and stem epidermis developed a smooth surface, with fewer serrated pavement cell (PC) lobes, and decreased papillae. The lpl2-1 also exhibited irregular stomata patterns, reduced plant height, and short panicles and roots. Molecular genetic studies demonstrated that LPL2 and LPL3 encode the PIROGI/Specifically Rac1 associated protein 1 (PIR/SRA1)-like and NCK-associated protein 1 (NAP1)-like proteins, respectively, two components of the suppressor of cAMP receptor/Wiskott Aldrich syndrome protein-family verprolin-homologous protein (SCAR/WAVE) regulatory complex involved in actin nucleation and function. Epidermal cells exhibited abnormal arrangement of F-actins in both lpl2 and lpl3 expanding leaves. Moreover, the distorted trichomes of Arabidopsis pir could be partially restored by an overexpression of LPL2 A yeast two-hybrid assay revealed that LPL2 can directly interact with LPL3 in vitro Collectively, the results indicate that LPL2 and LPL3 are two functionally conserved homologs of the SCAR/WAVE complex components, and that they play an important role in controlling epidermal cell morphogenesis in rice by organising F-actin. PMID- 27252471 TI - Myo-inositol phosphate synthase expression in the European eel (Anguilla anguilla) and Nile tilapia (Oreochromis niloticus): effect of seawater acclimation. AB - A single MIPS gene (Isyna1/Ino1) exists in eel and tilapia genomes with a single myo-d-inositol 3-phosphate synthase (MIPS) transcript identified in all eel tissues, although two MIPS spliced variants [termed MIPS(s) and MIPS(l)] are found in all tilapia tissues. The larger tilapia transcript [MIPS(l)] results from the inclusion of the 87-nucleotide intron between exons 5 and 6 in the genomic sequence. In most tilapia tissues, the MIPS(s) transcript exhibits much higher abundance (generally >10-fold) with the exception of white skeletal muscle and oocytes, in which the MIPS(l) transcript predominates. SW acclimation resulted in large (6- to 32-fold) increases in mRNA expression for both MIPS(s) and MIPS(l) in all tilapia tissues tested, whereas in the eel, changes in expression were limited to a more modest 2.5-fold increase and only in the kidney. Western blots identified a number of species- and tissue-specific immunoreactive MIPS proteins ranging from 40 to 67 kDa molecular weight. SW acclimation failed to affect the abundance of any immunoreactive protein in any tissue tested from the eel. However, a major 67-kDa immunoreactive protein (presumed to be MIPS) found in tilapia tissues exhibited 11- and 54-fold increases in expression in gill and fin samples from SW-acclimated fish. Immunohistochemical investigations revealed specific immunoreactivity in the gill, fin, skin, and intestine taken from only SW-acclimated tilapia. Immunofluorescence indicated that MIPS was expressed within gill chondrocytes and epithelial cells of the primary filaments, basal epithelial cell layers of the skin and fin, the cytosol of columnar intestinal epithelial and mucous cells, as well as unknown entero-endocrine-like cells. PMID- 27252470 TI - New antiepileptic drugs: focus on ezogabine, clobazam, and perampanel. AB - Ezogabine, clobazam, and perampanel are among the newest antiseizure drugs approved by the Food and Drug Administration between 2011 and 2012. Ezogabine and perampanel are approved for adjunctive treatment of partial epilepsy. Perampanel is also approved for adjunctive treatment of primary generalized tonic-clonic seizures. Ezogabine and perampanel have novel mechanisms of action. Ezogabine binds to voltage-gated potassium channels and increases the M-current thereby causing membrane hyperpolarization. Perampanel is a selective, non-competitive 2 amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptor antagonist, which reduces neuronal excitation. Clobazam has been used worldwide since the 1970s and is approved for adjunctive treatment of seizures associated with Lennox Gastaut syndrome. Clobazam is the only 1,5-benzodiazepine currently in clinical use, which is less sedating than the commonly used 1,4-benzodiazepines. Phase III multicenter, randomized, double-blind, placebo-controlled trials demonstrated efficacy and good tolerability of these 3 new antiepileptic drugs. These drugs represent a welcome addition to the armamentarium of practitioners, but it remains to be seen how they will affect the landscape of pharmacoresistant epilepsy. PMID- 27252472 TI - Chronic intermittent hypoxia accelerates coronary microcirculatory dysfunction in insulin-resistant Goto-Kakizaki rats. AB - Chronic intermittent hypoxia (IH) induces oxidative stress and inflammation, which impair vascular endothelial function. Long-term insulin resistance also leads to endothelial dysfunction. We determined, in vivo, whether the effects of chronic IH and insulin resistance on endothelial function augment each other. Male 12-wk-old Goto-Kakizaki (GK) and Wistar control rats were subjected to normoxia or chronic IH (90-s N2, 5% O2 at nadir, 90-s air, 20 cycles/h, 8 h/day) for 4 wk. Coronary endothelial function was assessed using microangiography with synchrotron radiation. Imaging was performed at baseline, during infusion of acetylcholine (ACh, 5 MUg.kg(-1).min(-1)) and then sodium nitroprusside (SNP, 5 MUg.kg(-1).min(-1)), after blockade of both nitric oxide (NO) synthase (NOS) with N(omega)-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg) and cyclooxygenase (COX, meclofenamate, 3 mg/kg), and during subsequent ACh. In GK rats, coronary vasodilatation in response to ACh and SNP was blunted compared with Wistar rats, and responses to ACh were abolished after blockade. In Wistar rats, IH blunted the ability of ACh or SNP to increase the number of visible vessels. In GK rats exposed to IH, neither ACh nor SNP were able to increase visible vessel number or caliber, and blockade resulted in marked vasoconstriction. Our findings indicate that IH augments the deleterious effects of insulin resistance on coronary endothelial function. They appear to increase the dependence of the coronary microcirculation on NO and/or vasodilator prostanoids, and greatly blunt the residual vasodilation in response to ACh after blockade of NOS/COX, presumably mediated by endothelium-derived hyperpolarizing factors. PMID- 27252473 TI - Sexually dimorphic myeloid inflammatory and metabolic responses to diet-induced obesity. AB - It is well known in clinical and animal studies that women and men have different disease risk as well as different disease physiology. Women of reproductive age are protected from metabolic and cardiovascular disease compared with postmenopausal women and men. Most murine studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of similar protection in female mice. We have investigated dietary obesity in a mouse model and have directly compared inflammatory responses in males and females. In this review we will summarize what is known about sex differences in diet-induced inflammation and will summarize our data on this topic. It is clear that sex differences in high-fat diet-induced inflammatory activation are due to cell intrinsic differences in hematopoietic responses to obesogenic cues, but further research is needed to understand what leads to sexually dimorphic responses. PMID- 27252474 TI - Nax signaling evoked by an increase in [Na+] in CSF induces water intake via EET mediated TRPV4 activation. AB - Water-intake behavior is under the control of brain systems that sense body fluid conditions at sensory circumventricular organs (sCVOs); however, the underlying mechanisms have not yet been elucidated in detail. Nax is a sodium (Na(+)) level sensor in the brain, and the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 have been proposed to function as osmosensors. We herein investigated voluntary water intake immediately induced after an intracerebroventricular administration of a hypertonic NaCl solution in TRPV1-, TRPV4-, Nax-, and their double-gene knockout (KO) mice. The induction of water intake by TRPV1-KO mice was normal, whereas intake by TRPV4-KO and Nax-KO mice was significantly less than that by WT mice. Water intake by Nax/TRPV4-double KO mice was similar to that by the respective single KO mice. When TRPV4 activity was blocked with a specific antagonist HC-067047, water intake by WT mice was significantly reduced, whereas intake by TRPV4-KO and Nax-KO mice was not. Similar results were obtained with the administration of miconazole, which inhibits the biosynthesis of epoxyeicosatrienoic acids (EETs), endogenous agonists for TRPV4, from arachidonic acid (AA). Intracerebroventricular injection of hypertonic NaCl with AA or 5,6-EET restored water intake by Nax-KO mice to the wild-type level but not that by TRPV4-KO mice. These results suggest that the Na(+) signal generated in Nax-positive glial cells leads to the activation of TRPV4-positive neurons in sCVOs to stimulate water intake by using EETs as gliotransmitters. Intracerebroventricular injection of equiosmolar hypertonic sorbitol solution induced small but significant water intake equally in all the genotypes, suggesting the presence of an unknown osmosensor in the brain. PMID- 27252476 TI - Frontiers in heart failure: assessement, risk factors, and novel genetic and cell based therapies. PMID- 27252477 TI - CardioPulse Articles. PMID- 27252475 TI - Defining the Effectiveness of Antimalarial Chemotherapy: Investigation of the Lag in Parasite Clearance Following Drug Administration. AB - BACKGROUND: The emergence of drug-resistant malaria highlights the need for new agents. A desired characteristic of candidate antimalarials is rapid killing of parasites. This is typically measured by the rate of exponential clearance of parasitemia following treatment. However, this clearance rate excludes the highly variable lag phase, when the parasitemia level may increase, remain constant, or decrease. Understanding factors determining this lag phase is important for drug development. METHODS: We assessed the kinetics of parasitemia in 112 volunteers infected with blood-stage Plasmodium falciparum and treated with 8 different antimalarials. The parasitemia level was measured by quantitative polymerase chain reaction. We analyzed the relationship between the timing of treatment in the parasite growth cycle, and whether the parasitemia level rose or fell in the first 12 or 24 hours after treatment. RESULTS: The timing of treatment in the parasite life cycle predicted whether subjects experienced rises or falls in parasitemia level after treatment. Antimalarials were unable to prevent rises in the parasitemia level in the first 12 hours. However, in the first 24 hours after treatment, fast-acting but not slow-acting drugs reduced the parasitemia level independent of when treatment was administered. CONCLUSIONS: The highly variable lag phase depends on the speed of action of an antimalarial and when in the periodic growth cycle it is administered. PMID- 27252478 TI - Extensive Cutaneous Larva Migrans with Eczematous Reaction on Atypical Localization. PMID- 27252479 TI - Approaches to Evaluate the Impact of Community-Based Delivery Strategies. PMID- 27252480 TI - Independent Evaluation of the Integrated Community Case Management of Childhood Illness Strategy in Malawi Using a National Evaluation Platform Design. PMID- 27252481 TI - Splenectomy or Partial Splenectomy Should be Preferred Treatment for Large Splenic Hydatid Cysts. PMID- 27252482 TI - Varroa destructor (Mesostigmata: Varroidae) Parasitism and Climate Differentially Influence the Prevalence, Levels, and Overt Infections of Deformed Wing Virus in Honey Bees (Hymenoptera: Apidae). AB - The prevalence and loads of deformed wing virus (DWV) between honey bee (Apis mellifera L.) colonies from a tropical and a temperate environment were compared. The interaction between these environments and the mite Varroa destructor in relation to DWV prevalence, levels, and overt infections, was also analyzed. V. destructor rates were determined, and samples of mites, adult bees, brood parasitized with varroa mites and brood not infested by mites were analyzed. DWV was detected in 100% of the mites and its prevalence and loads in honey bees were significantly higher in colonies from the temperate climate than in colonies from the tropical climate. Significant interactions were found between climate and type of sample, with the highest levels of DWV found in varroa-parasitized brood from temperate climate colonies. Additionally, overt infections were observed only in the temperate climate. Varroa parasitism and DWV loads in bees from colonies with overt infections were significantly higher than in bees from colonies with covert infections. These results suggest that interactions between climate, V. destructor, and possibly other factors, may play a significant role in the prevalence and levels of DWV in honey bee colonies, as well as in the development of overt infections. Several hypotheses are discussed to explain these results. PMID- 27252483 TI - Saproxylic Beetle Assemblage Selection as Determining Factor of Species Distributional Patterns: Implications for Conservation. AB - The knowledge of the distributional patterns of saproxylic beetles is essential for conservation biology due to the relevance of this fauna in the maintenance of ecological processes and the endangerment of species. The complex community of saproxylic beetles is shaped by different assemblages that are composed of species linked by the microhabitats they use. We evaluate how different the species distribution patterns that are obtained can be, depending on the analyzed assemblage and to what extent these can affect conservation decisions. Beetles were sampled using hollow emergence and window traps in three protected areas of the Iberian Peninsula. Species richness, composition, and diversity turnover were analyzed for each sampling method and showed high variation depending on the analyzed assemblage. Beta diversity was clearly higher among forests for the assemblage captured using window traps. This method collects flying insects from different tree microhabitats and its captures are influenced by the forest structuring. Within forests, the assemblages captured by hollow emergence traps, which collect the fauna linked to tree hollows, showed the largest turnover of species, as they are influenced by the characteristics of each cavity. Moreover, the selection of the forest showing the highest species richness strongly depended on the studied assemblage. This study demonstrates that differences in the studied assemblages (group of species co-occurring in the same habitat) can also lead to significant differences in the identified patterns of species distribution and diversity turnover. This fact will be necessary to take into consideration when making decisions about conservation and management. PMID- 27252484 TI - ENDOCRINE TUMOURS: Imaging in the follow-up of differentiated thyroid cancer: current evidence and future perspectives for a risk-adapted approach. AB - The clinical and epidemiological profiles of differentiated thyroid cancers (DTCs) have changed in the last three decades. Today's DTCs are more likely to be small, localized, asymptomatic papillary forms. Current practice is, though, moving toward more conservative approaches (e.g. lobectomy instead of total thyroidectomy, selective use of radioiodine). This evolution has been paralleled and partly driven by rapid technological advances in the field of diagnostic imaging. The challenge of contemporary DTCs follow-up is to tailor a risk-of recurrence-based management, taking into account the dynamic nature of these risks, which evolve over time, spontaneously and in response to treatments. This review provides a closer look at the evolving evidence-based views on the use and utility of imaging technology in the post-treatment staging and the short- and long-term surveillance of patients with DTCs. The studies considered range from cervical US with Doppler flow analysis to an expanding palette of increasingly sophisticated second-line studies (cross-sectional, functional, combined-modality approaches), which can be used to detect disease that has spread beyond the neck and, in some cases, shed light on its probable outcome. PMID- 27252485 TI - A homozygous point mutation in the GH1 promoter (c.-223C>T) leads to reduced GH1 expression in siblings with isolated GH deficiency (IGHD). AB - CONTEXT: Mutations in the GH1 promoter are a rare cause of isolated growth hormone deficiency (IGHD). OBJECTIVE: To identify the molecular aetiology of a family with IGHD. DESIGN: DNA sequencing, electromobility shift (EMSA) and luciferase reporter assays. SETTING: University Hospital. PATIENTS: Three siblings (2M) born to consanguineous parents presented with IGHD with normal pituitary on MRI. METHODS: The GH1 proximal promoter, locus control region, five exons and four introns as well as GHRHR gene were sequenced in genomic DNA by Sanger method. DNA-protein interaction was evaluated by EMSA in nuclear extracts of GH3 pituitary cells. Dual-luciferase reporter assays were performed in cells transiently transfected with plasmids containing four different combinations of GH1 allelic variants (AV). RESULTS: The patients harboured two homozygous variants (c.-185T>C and c.-223C>T) in the GH1 promoter within a highly conserved region and predicted binding sites for POU1F1/SP1 and SP1 respectively. The parents and brother were carriers and these variants were absent in 100 controls. EMSA demonstrated absent binding of GH3 nuclear extract to the c.-223C>T variant and normal binding of both POU1F1 protein and GH3 nuclear extract to the c. 185T>C variant. In contrast to GH1 promoter with AV only at c.-185, the GH1 promoter containing the AV only at c.-223 and at both positions drove significantly less expression of luciferase compared with the promoter containing either positions wild type in luciferase reporter assays. CONCLUSION: To our knowledge, c.-223C>T is the first homozygous point mutation in the GH1 promoter that leads to short stature due to IGHD. PMID- 27252486 TI - Endocrine and metabolic diurnal rhythms in young adult men born small vs appropriate for gestational age. AB - OBJECTIVE: Sleep disturbances and alterations of diurnal endocrine rhythms are associated with increased risk of type 2 diabetes (T2D). We previously showed that young men born small for gestational age (SGA) and with increased risk of T2D have elevated fat and decreased glucose oxidation rates during nighttime. In this study, we investigated whether SGA men have an altered diurnal profile of hormones, substrates and inflammatory markers implicated in T2D pathophysiology compared with matched individuals born appropriate for gestational age (AGA). METHODS: We collected hourly blood samples for 24 h, to measure levels of glucose, free fatty acids (FFA), triglycerides (TG), insulin, C-peptide, leptin, resistin, ghrelin, plasminogen activator inhibitor-1 (PAI-1), incretins (GLP-1 and GIP), and inflammatory markers (TNF-alpha and IL-6) in 13 young men born SGA and 11 young men born AGA. RESULTS: Repeated measurements analyses were used to analyze the diurnal variations and differences between groups. The SGA subjects had increased 24-h glucose (P=0.03), glucagon (P=0.03) and resistin (P=0.003) levels with no difference in diurnal rhythms compared with AGA controls. We found significant diurnal variations in levels of blood glucose, plasma TG, FFA, insulin, C-peptide, GLP-1, GIP, leptin, visfatin, TNF-alpha, IL-6 and PAI-1. The variation in FFA levels differed between the groups during the evening. Plasma ghrelin and glucagon levels did not display diurnal variations. CONCLUSIONS: Young men born SGA exhibit elevated 24-h blood glucose, and plasma glucagon and resistin levels with no major differences in diurnal rhythms of these or other key metabolic hormones, substrates or inflammatory markers implicated in the origin of adiposity and T2D. PMID- 27252487 TI - Quantification of paravalvular regurgitation after transcatheter aortic valve implantation: improved accuracy means better standardization. PMID- 27252489 TI - Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia. AB - Sepsis is an uncontrolled systemic inflammatory response against an infection and a major public health issue worldwide. This condition affects several organs, and, when caused by Gram-negative bacteria, kidneys are particularly damaged. Due to the importance of renin-angiotensin system (RAS) in regulating renal function, in the present study, we aimed to investigate the effects of endotoxemia over the renal RAS. Wistar rats were injected with Escherichia coli lipopolysaccharide (LPS) (4 mg/kg), mimicking the endotoxemia induced by Gram-negative bacteria. Three days after treatment, body mass, blood pressure, and plasma nitric oxide (NO) were reduced, indicating that endotoxemia triggered cardiovascular and metabolic consequences and that hypotension was maintained by NO-independent mechanisms. Regarding the effects in renal tissue, inducible NO synthase (iNOS) was diminished, but no changes in the renal level of NO were detected. RAS was also highly affected by endotoxemia, since renin, angiotensin-converting enzyme (ACE), and ACE2 activities were altered in renal tissue. Although these enzymes were modulated, only angiotensin (ANG) II was augmented in kidneys; ANG I and ANG 1-7 levels were not influenced by LPS. Cathepsin G and chymase activities were increased in the endotoxemia group, suggesting alternative pathways for ANG II formation. Taken together, our data suggest the activation of noncanonical pathways for ANG II production and the presence of renal vasoconstriction and tissue damage in our animal model. In summary, the systemic administration of LPS affects renal RAS, what may contribute for several deleterious effects of endotoxemia over kidneys. PMID- 27252488 TI - Minor intron splicing is regulated by FUS and affected by ALS-associated FUS mutants. AB - Fused in sarcoma (FUS) is a ubiquitously expressed RNA-binding protein proposed to function in various RNA metabolic pathways, including transcription regulation, pre-mRNA splicing, RNA transport and microRNA processing. Mutations in the FUS gene were identified in patients with amyotrophic lateral sclerosis (ALS), but the pathomechanisms by which these mutations cause ALS are not known. Here, we show that FUS interacts with the minor spliceosome constituent U11 snRNP, binds preferentially to minor introns and directly regulates their removal. Furthermore, a FUS knockout in neuroblastoma cells strongly disturbs the splicing of minor intron-containing mRNAs, among them mRNAs required for action potential transmission and for functional spinal motor units. Moreover, an ALS associated FUS mutant that forms cytoplasmic aggregates inhibits splicing of minor introns by trapping U11 and U12 snRNAs in these aggregates. Collectively, our findings suggest a possible pathomechanism for ALS in which mutated FUS inhibits correct splicing of minor introns in mRNAs encoding proteins required for motor neuron survival. PMID- 27252490 TI - Low-dose testosterone protects against renal ischemia-reperfusion injury by increasing renal IL-10-to-TNF-alpha ratio and attenuating T-cell infiltration. AB - Renal ischemia-reperfusion (I/R) in male rats causes reductions in plasma testosterone, and infusion of testosterone 3 h postreperfusion is protective. We tested the hypotheses that acute high doses of testosterone promote renal injury after I/R, and that acute low-dose testosterone is protective by the following: 1) increasing renal IL-10 and reducing TNF-alpha; 2) its effects on nitric oxide; and 3) reducing intrarenal T-cell infiltration. Rats were subjected to renal I/R, followed by intravenous infusion of vehicle or testosterone (20, 50, or 100 MUg/kg) 3 h postreperfusion. Low-dose testosterone (20 MUg/kg) reduced plasma creatinine, increased nitrate/nitrite excretion, increased intrarenal IL-10, and reduced intrarenal TNF-alpha, whereas 50 MUg/kg testosterone failed to reduce plasma creatinine, increased IL-10, but failed to reduce TNF-alpha. A higher dose of testosterone (100 mg/kg) not only failed to reduce plasma creatinine, but significantly increased both IL-10 and TNF-alpha compared with other groups. Low dose nitro-l-arginine methyl ester (1 mg.kg(-1).day(-1)), given 2 days before I/R, prevented low-dose testosterone (20 MUg/kg) from protecting against I/R injury, and was associated with lack of increase in intrarenal IL-10. Intrarenal CD4(+) and CD8(+) T cells were significantly increased with I/R, but were attenuated with low-dose testosterone, as were effector T helper 17 cells. The present studies suggest that acute, low-dose testosterone is protective against I/R AKI in males due to its effects on inflammation by reducing renal T-cell infiltration and by shifting the balance to favor anti-inflammatory cytokine production rather than proinflammatory cytokines. PMID- 27252493 TI - Prospecting for Precision: Promises for Personalized Medicine. PMID- 27252491 TI - Late intervention with the small molecule BB3 mitigates postischemic kidney injury. AB - Ischemia-reperfusion-mediated acute kidney injury can necessitate renal replacement therapy and is a major cause of morbidity and mortality. We have identified BB3, a small molecule, which when first administered at 24 h after renal ischemia in rats, improved survival, augmented urine output, and reduced the increase in serum creatinine and blood urea nitrogen. Compared with control kidneys, the kidneys of BB3-treated animals exhibited reduced levels of kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and reduced tubular apoptosis and acute tubular necrosis but enhanced tubular regeneration. Consistent with its hepatocyte growth factor-like mode of action, BB3 treatment promoted phosphorylation of renal cMet and Akt and upregulated renal expression of the survival protein Bcl-2. These data suggest that the kidney is amenable to pharmacotherapy even 24 h after ischemia-reperfusion and that activation of the hepatocyte growth factor signaling pathway with the small molecule BB3 confers interventional benefits late into ischemia-reperfusion injury. These data formed, in part, the basis for the use of BB3 in a clinical trial in kidney recipients presenting with delayed graft function. PMID- 27252494 TI - Two Cases of Gouty Sacroiliitis Evaluated by Dual-energy Computed Tomography. PMID- 27252492 TI - Preconditioning mice with activators of AMPK ameliorates ischemic acute kidney injury in vivo. AB - This study had two objectives: 1) to determine whether preconditioning cultured proximal tubular cells (PTCs) with pharmacological activators of AMP-activated protein kinase (AMPK) protects these cells from apoptosis induced by metabolic stress in vitro and 2) to assess the effects of preconditioning mice with these agents on the severity of ischemic acute renal kidney injury (AKI) in vivo. We demonstrate that preconditioning PTCs with 5-aminoimidazole-4-carboxamide-1-beta d-ribofuranoside (AICAR) or A-769662 reduces apoptosis of PTCs induced by subsequent stress. We also show that the reduction in cell death during metabolic stress associated with pretreatment by AMPK activators is associated with an increase in the cytosolic level of ATP, which is mediated by an increase in the rate of glycolysis. In addition, we provide evidence that the effect of AMPK activators on glycolysis is mediated, at least in part, by an increased uptake of glucose, and by the induction of hexokinase II (HK II) expression. Our data also show that the increased in HK II expression associated with preconditioning with AMPK activators is mediated by the activation (phosphorylation) of the cAMP response element binding protein (CREB). We also provide entirely novel evidence that that A-79662 is substantially more effective than AICAR in mediating these alterations in PTCs in vitro. Finally, we demonstrate that preconditioning mice with AICAR or A-769662 substantially reduces the severity of renal dysfunction and tubular injury in a model of ischemic AKI in vivo and that the efficacy of AICAR and A-768662 in ameliorating ischemic AKI in vivo is comparable. PMID- 27252495 TI - Ultrasonography: A Useful Tool for the Diagnosis of Chondrocalcinosis of the Sternoclavicular Joint. PMID- 27252496 TI - Alar and Transverse Ligament Calcification and Crown Dens. PMID- 27252497 TI - The Importance of Linking Primary and Secondary Electronic Medical Records. PMID- 27252498 TI - Dr. Takizawa, et al reply. PMID- 27252499 TI - Dr. Matteson and Ms. Crowson reply. PMID- 27252500 TI - Predictors of Biological Antirheumatic Drug Discontinuation in Patients with Rheumatoid Arthritis while in Remission. PMID- 27252501 TI - Dr. Yoshida, et al reply. PMID- 27252502 TI - Retinopathy in the Era of Routine Hydroxychloroquine Monitoring. PMID- 27252503 TI - HLA-B*40:01 Is Associated with Ankylosing Spondylitis in HLA-B27-positive Populations. PMID- 27252504 TI - Dr. Durcan, et al reply. PMID- 27252505 TI - MRI Protocol for the Assessment of Juvenile Idiopathic Arthritis of the Wrist: Recommendations from the OMERACT MRI in JIA Working Group and Health-e-Child. PMID- 27252506 TI - Phenotypic Variability in Majeed Syndrome. PMID- 27252507 TI - Primary Sjogren Syndrome in a Child with a Neuromyelitis Optica Spectrum Disorder. PMID- 27252508 TI - The optimal dosing of gemtuzumab ozagamicin: where to go from here? PMID- 27252509 TI - HOXA-activated early T-cell progenitor acute lymphoblastic leukemia: predictor of poor outcome? PMID- 27252510 TI - Innovation in hematology. Perspectives: CML 2016. PMID- 27252511 TI - Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies. AB - Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-beta, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment. PMID- 27252512 TI - Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia. AB - Wilms tumor 1 (WT1) has long been implicated in acute myeloid leukemia. It has been described to be both overexpressed and mutated in different forms of acute myeloid leukemia, and overexpression has been reported to play a prognostic role in this disease. However, the precise mechanism through which WT1 may play a role in leukemogenesis has remained elusive. In recent years, new evidence has emerged that points towards a novel role of WT1 mutations in the deregulation of epigenetic programs in leukemic cells through its interaction with TET proteins. Herein we review the current status of the field and its therapeutic and prognostic implications in acute myeloid leukemia. PMID- 27252513 TI - How to select the best available related or unrelated donor of hematopoietic stem cells? AB - Recognition of HLA incompatibilities by the immune system represents a major barrier to allogeneic hematopoietic stem cell transplantation. HLA genotypically identical sibling donors are, therefore, the gold standard for transplantation purposes, but only 30% patients have such a donor. For the remaining 70% patients alternative sources of stem cells are a matched unrelated adult volunteer donor, a haploidentical donor or a cord blood unit. The definition of 'HLA matching' depends on the level of resolution and on which loci are tested. The development of HLA molecular typing technologies and the availability of more than 27 million donors in the international database has greatly facilitated unrelated donor searches. The gold standard is high resolution typing at the HLA-A, -B, -C, DRB1, and -DQB1 loci (10/10 match). Single disparities for HLA-A, -B, - C, or DRB1 are associated with increased risk of post-transplant complications, but less so in patients with advanced disease, and in those undergoing T-cell depleted allografting. HLA-DQB1 mismatches seem to be better tolerated and some HLA-C, -DRB1 and -DPB1 disparities are potentially less immunogenic. HLA typing by next-generation sequencing methods is likely to change matching algorithms by providing full sequence information on all HLA loci in a single step. In most European populations a 10/10 matched donor can be found for at least 50% of patients and an additional 20-30% patients may have a 9/10 matched donor. Genetic factors that help in identifying donors with less immunogenic mismatches are discussed. Haploidentical donors are increasingly used as an alternative source of stem cells for those patients lacking a matched unrelated donor. PMID- 27252514 TI - A milder clinical course for severe hemophilia B: a true or biased effect? PMID- 27252515 TI - Efficacy and safety of second-line ponatinib after failure of a single previous tyrosine kinase inhibitor for chronic myeloid leukemia patients in chronic phase. PMID- 27252516 TI - Comment on: Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma, by Yoo et al. PMID- 27252517 TI - Author reply to Comment on: Frequent CTLA4-CD28 gene fusion in diverse types of T cell lymphoma, by Yoo et al. PMID- 27252518 TI - Retroperitoneal calcifying fibrous tumor mimicking an adrenal tumor. AB - Establishing the etiology of a retroperitoneal tumor may be difficult due to close proximity of multiple organs. Evaluation of retroperitoneal tumors often leads to surgery, many times to obtain a definitive diagnosis and rule out malignancy. Calcifying fibrous tumors (CFT) are very rare soft tissue tumors occurring most often in young patients. They are most often found arising in the thoracic cavity, mediastinum, abdominal cavity and extremities and usually have a benign clinical course. Macrocscopically, the tumors are well circumscribed and firm with a white-tan appearance. Histologically, CFT comprised a hypocellular proliferation of bland spindle cells, densely hyalinized collagen, chronic lymphoplasmacytic inflammation and dystrophic calcifications. Other considerations in the pathologic differential diagnosis include solitary fibrous tumor and inflammatory myofibroblastic tumor. PMID- 27252519 TI - Blunt traumatic infrarenal aortic intimal flap progressing to pseudoaneurysm over 3 months. AB - Blunt traumatic infrarenal aortic injuries are unusual, and the formation of a delayed pseudoaneurysm of the aorta is even more rare. In this report, a young woman developed a small intimal flap of the infrarenal aorta after a motor vehicle accident which progressed into a 3 cm pseudoaneurysm after 3 months. Operative repair was successful and the patient recovered. This case illustrates the importance of repeat imaging of small blunt aortic injuries since progression can occur. PMID- 27252520 TI - Theatrical fire pursuant exploratory laparotomy. AB - Fire in the operating theater is a rare but potentially fatal complication. We report igniting an intraperitoneal fire while preforming an exploratory laparotomy for perforated viscus. Fortunately, the patient suffered no injuries as a result. PMID- 27252521 TI - Editorial: An ATRA oddity: new questions revealed on retinoid synthesis in bone marrow cells. PMID- 27252522 TI - Editorial: "Invisible" MDSC in tumor-bearing individuals after antibody depletion: fact or fiction? PMID- 27252523 TI - E4BP4 is an insulin-induced stabilizer of nuclear SREBP-1c and promotes SREBP-1c mediated lipogenesis. AB - Upon food intake, insulin stimulates de novo lipogenesis (DNL) in hepatocytes via the AKT-mTORC1-sterol regulatory element-binding protein (SREBP)-1c pathway. How insulin maintains the maximal SREBP-1c activities during the entire feeding state remains elusive. We previously reported that insulin induced b-ZIP transcription factor, E4-binding protein 4 (E4BP4), in hepatocytes. In the current study, we show that insulin injection increases hepatic E4bp4 expression by activating the AKT-mTORC1-SREBP-1c pathway in hepatocytes. E4bp4-deficient hepatocytes not only fail to maintain robust DNL but also become resistant to SREBP-1c-induced lipogenesis. In vivo, acute depletion of E4bp4 in the liver by adenoviral shRNA reduces the expression of lipogenic enzymes and results in reduced levels of serum triglycerides and cholesterol during the postprandial phase. In hepatocytes, E4BP4 interacts with nuclear SREBP-1c to preserve its acetylation, and subsequently protects it from ubiquitination-dependent degradation. In conclusion, the current studies uncover a novel positive feedback pathway mediated by E4BP4 to augment SREBP-1c-mediated DNL in the liver during the fed state. PMID- 27252524 TI - Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation. AB - Chronic hepatitis B (CHB) is prevalent worldwide. The infectious agent, hepatitis B virus (HBV), replicates via an RNA intermediate and is error prone, leading to the rapid generation of closely related but not identical viral variants, including those that can escape host immune responses and antiviral treatments. The complexity of CHB can be further enhanced by the presence of HBV variants with large deletions in the genome generated via splicing (spHBV variants). Although spHBV variants are incapable of autonomous replication, their replication is rescued by wild-type HBV. spHBV variants have been shown to enhance wild-type virus replication, and their prevalence increases with liver disease progression. Single-molecule deep sequencing was performed on whole HBV genomes extracted from samples, including the liver explant, longitudinally collected from a subject with CHB over a 15-year period after liver transplantation. By employing novel bioinformatics methods, this analysis showed that the dynamics of the viral population across a period of changing treatment regimens was complex. The spHBV variants detected in the liver explant remained present posttransplantation, and a highly diverse novel spHBV population as well as variants with multiple deletions in the pre-S genes emerged. The identification of novel mutations outside the HBV reverse transcriptase gene that co-occurred with known drug resistance-associated mutations highlights the relevance of using full-genome deep sequencing and supports the hypothesis that drug resistance involves interactions across the full length of the HBV genome. IMPORTANCE: Single-molecule sequencing allowed the characterization, in unprecedented detail, of the evolution of HBV populations and offered unique insights into the dynamics of defective and spHBV variants following liver transplantation and complex treatment regimens. This analysis also showed the rapid adaptation of HBV populations to treatment regimens with evolving drug resistance phenotypes and evidence of purifying selection across the whole genome. Finally, the new open-source bioinformatics tools with the capacity to easily identify potential spliced variants from deep sequencing data are freely available. PMID- 27252525 TI - Nonstructural 3 Protein of Hepatitis C Virus Modulates the Tribbles Homolog 3/Akt Signaling Pathway for Persistent Viral Infection. AB - Hepatitis C virus (HCV) infection often causes chronic hepatitis, liver cirrhosis, and ultimately hepatocellular carcinoma. However, the mechanisms underlying HCV-induced liver pathogenesis are still not fully understood. By transcriptome sequencing (RNA-Seq) analysis, we recently identified host genes that were significantly differentially expressed in cell culture-grown HCV (HCVcc)-infected cells. Of these, tribbles homolog 3 (TRIB3) was selected for further characterization. TRIB3 was initially identified as a binding partner of protein kinase B (also known as Akt). TRIB3 blocks the phosphorylation of Akt and induces apoptosis under endoplasmic reticulum (ER) stress conditions. HCV has been shown to enhance Akt phosphorylation for its own propagation. In the present study, we demonstrated that both mRNA and protein levels of TRIB3 were increased in the context of HCV replication. We further showed that promoter activity of TRIB3 was increased by HCV-induced ER stress. Silencing of TRIB3 resulted in increased RNA and protein levels of HCV, whereas overexpression of TRIB3 decreased HCV replication. By employing an HCV pseudoparticle entry assay, we further showed that TRIB3 was a negative host factor involved in HCV entry. Both in vitro binding and immunoprecipitation assays demonstrated that HCV NS3 specifically interacted with TRIB3. Consequently, the association of TRIB3 and Akt was disrupted by HCV NS3, and thus, TRIB3-Akt signaling was impaired in HCV infected cells. Moreover, HCV modulated TRIB3 to promote extracellular signal regulated kinase (ERK) phosphorylation, activator protein 1 (AP-1) activity, and cell migration. Collectively, these data indicate that HCV exploits the TRIB3-Akt signaling pathway to promote persistent viral infection and may contribute to HCV mediated pathogenesis. IMPORTANCE: TRIB3 is a pseudokinase protein that acts as an adaptor in signaling pathways for important cellular processes. So far, the functional involvement of TRIB3 in virus-infected cells has not yet been demonstrated. We showed that both mRNA and protein expression levels of TRIB3 were increased in the context of HCV RNA replication. Gene silencing of TRIB3 increased HCV RNA and protein levels, and thus, overexpression of TRIB3 decreased HCV replication. TRIB3 is known to promote apoptosis by negatively regulating the Akt signaling pathway under ER stress conditions. Most importantly, we demonstrated that the TRIB3-Akt signaling pathway was disrupted by NS3 in HCV infected cells. These data provide evidence that HCV modulates the TRIB3-Akt signaling pathway to establish persistent viral infection. PMID- 27252527 TI - Mutants at the 2-Fold Interface of Adeno-associated Virus Type 2 (AAV2) Structural Proteins Suggest a Role in Viral Transcription for AAV Capsids. AB - We previously reported that an amino acid substitution, Y704A, near the 2-fold interface of adeno-associated virus (AAV) was defective for transcription of the packaged genome (M. Salganik, F. Aydemir, H. J. Nam, R. McKenna, M. Agbandje McKenna, and N. Muzyczka, J Virol 88:1071-1079, 2013, doi: http://dx.doi.org/10.1128/JVI.02093-13). In this report, we have characterized the defect in 6 additional capsid mutants located in a region ~30 A in diameter on the surface of the AAV type 2 (AAV2) capsid near the 2-fold interface. These mutants, which are highly conserved among primate serotypes, displayed a severe defect (3 to 6 logs) in infectivity. All of the mutants accumulated significant levels of uncoated DNA in the nucleus, but none of the mutants were able to accumulate significant amounts of genomic mRNA postinfection. In addition, wild type (wt) capsids that were bound to the conformational antibody A20, which is known to bind the capsid surface in the region of the mutants, were also defective for transcription. In all cases, the mutant virus particles, as well as the antibody-bound wild-type capsids, were able to enter the cell, travel to the nucleus, uncoat, and synthesize a second strand but were unable to transcribe their genomes. Taken together, the phenotype of these mutants provides compelling evidence that the AAV capsid plays a role in the transcription of its genome, and the mutants map this functional region on the surface of the capsid near the 2 fold interface. This appears to be the first example of a viral structural protein that is also involved in the transcription of the viral genome that it delivers to the nucleus. IMPORTANCE: Many viruses package enzymes within their capsids that assist in expressing their genomes postinfection, e.g., retroviruses. A number of nonenveloped viruses, including AAV, carry proteases that are needed for capsid maturation or for capsid modification during infection. We describe here what appears to be the first example of a nonenveloped viral capsid that appears to have a role in promoting transcription. A total of six mutants at the AAV capsid 2-fold interface were shown to have a severe defect in expressing their genomes, and the defect was at the level of mRNA accumulation. This suggests that AAV capsids have a novel role in promoting the transcription of the genomes that they have packaged. Since wt virions could not complement the mutant viruses, and the mutant viruses did not effectively inhibit wt gene expression, our results suggest that the capsid exerts its effect on transcription in cis. PMID- 27252526 TI - Interaction between Nonstructural Proteins NS4B and NS5A Is Essential for Proper NS5A Localization and Hepatitis C Virus RNA Replication. AB - The hepatitis C virus NS5A protein is tethered to cellular membranes via an amphipathic amino-terminal helix that is inserted in-plane into the outer endoplasmic reticulum (ER)-derived membrane leaflet. The charged face of the helix faces the cytoplasm and may contribute to interactions involved in replicase assembly and function. Using an aggressive charge flip mutagenesis strategy, we identified a number of essential residues for replication on the charged face of the NS5A anchor and identified a double charge face mutant that is lethal for RNA replication but generates suppressor mutations in the carboxy terminal helix of the NS4B protein. This suppressor restores RNA replication of the NS5A helix double flip mutant (D1979K/D1982K) and, interestingly, seems to function by restoring the proper localization of NS5A to the viral replicase. These data add to our understanding of the complex organization and assembly of the viral replicase via NS4B-NS5A interactions. IMPORTANCE: Information about the functional role of the cytosolic face of the NS5A anchoring helix remains obscure. In this study, we show that while the hydrophobic face of the NS5A anchor helix mediates membrane association, the polar cytosolic face of the helix plays a key role during hepatitis C virus (HCV) replication by mediating the interaction of NS5A with other HCV nonstructural proteins via NS4B. Such an interaction determines the subcellular localization of NS5A by engaging NS5A in the HCV replication process during the formation of a functional HCV replication complex. Thus, collectively, it can be stated that the findings in the present study provide further information about the interactions between the HCV nonstructural proteins during HCV RNA replication and provide a platform to gain more insights about the molecular architecture of HCV replication complexes. PMID- 27252528 TI - Mutagenesis of S-Adenosyl-l-Methionine-Binding Residues in Coronavirus nsp14 N7 Methyltransferase Demonstrates Differing Requirements for Genome Translation and Resistance to Innate Immunity. AB - Eukaryotic mRNAs possess a methylated 5'-guanosine cap that is required for RNA stability, efficient translation, and protection from cell-intrinsic defenses. Many viruses use 5' caps or other mechanisms to mimic a cap structure to limit detection of viral RNAs by intracellular innate sensors and to direct efficient translation of viral proteins. The coronavirus (CoV) nonstructural protein 14 (nsp14) is a multifunctional protein with N7-methyltransferase (N7-MTase) activity. The highly conserved S-adenosyl-l-methionine (SAM)-binding residues of the DxG motif are required for nsp14 N7-MTase activity in vitro However, the requirement for CoV N7-MTase activity and the importance of the SAM-binding residues during viral replication have not been determined. Here, we engineered mutations in murine hepatitis virus (MHV) nsp14 N7-MTase at residues D330 and G332 and determined the effects of these mutations on viral replication, sensitivity to mutagen, inhibition by type I interferon (IFN), and translation efficiency. Virus encoding a G332A substitution in nsp14 displayed delayed replication kinetics and decreased peak titers relative to wild-type (WT) MHV. In addition, replication of nsp14 G332A virus was diminished following treatment of cells with IFN-beta, and nsp14 G332A genomes were translated less efficiently both in vitro and during viral infection. In contrast, substitution of alanine at MHV nsp14 D330 did not affect viral replication, sensitivity to mutagen, or inhibition by IFN-beta compared to WT MHV. Our results demonstrate that the conserved MHV N7-MTase SAM-binding-site residues are not required for MHV viability and suggest that the determinants of CoV N7-MTase activity differ in vitro and during virus infection. IMPORTANCE: Human coronaviruses, most notably severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, cause severe and lethal human disease. Since specific antiviral therapies are not available for the treatment of human coronavirus infections, it is essential to understand the functions of conserved CoV proteins in viral replication. Here, we show that substitution of alanine at G332 in the N7-MTase domain of nsp14 impairs viral replication, enhances sensitivity to the innate immune response, and reduces viral RNA translation efficiency. Our data support the idea that coronavirus RNA capping could be targeted for development of antiviral therapeutics. PMID- 27252529 TI - Time-Dependent Rate Phenomenon in Viruses. AB - Among the most fundamental questions in viral evolutionary biology are how fast viruses evolve and how evolutionary rates differ among viruses and fluctuate through time. Traditionally, viruses are loosely classed into two groups: slow evolving DNA viruses and fast-evolving RNA viruses. As viral evolutionary rate estimates become more available, it appears that the rates are negatively correlated with the measurement timescales and that the boundary between the rates of DNA and RNA viruses might not be as clear as previously thought. In this study, we collected 396 viral evolutionary rate estimates across almost all viral genome types and replication strategies, and we examined their rate dynamics. We showed that the time-dependent rate phenomenon exists across multiple levels of viral taxonomy, from the Baltimore classification viral groups to genera. We also showed that, by taking the rate decay dynamics into account, a clear division between the rates of DNA and RNA viruses as well as reverse-transcribing viruses could be recovered. Surprisingly, despite large differences in their biology, our analyses suggested that the rate decay speed is independent of viral types and thus might be useful for better estimation of the evolutionary time scale of any virus. To illustrate this, we used our model to reestimate the evolutionary timescales of extant lentiviruses, which were previously suggested to be very young by standard phylogenetic analyses. Our analyses suggested that these viruses are millions of years old, in agreement with paleovirological evidence, and therefore, for the first time, reconciled molecular analyses of ancient and extant viruses. IMPORTANCE: This work provides direct evidence that viral evolutionary rate estimates decay with their measurement timescales and that the rate decay speeds do not differ significantly among viruses despite the vast differences in their molecular features. After adjustment for the rate decay dynamics, the division between the rates of double-stranded DNA (dsDNA), single stranded RNA (ssRNA), and ssDNA/reverse-transcribing viruses could be seen more clearly than before. Our results provide a guideline for further improvement of the molecular clock. As a demonstration of this, we used our model to reestimate the timescales of modern lentiviruses, which were previously thought to be very young, and concluded that they are millions of years old. This result matches the estimate from paleovirological analyses, thus bridging the gap between ancient and extant viral evolutionary studies. PMID- 27252530 TI - Ebola Virus Does Not Induce Stress Granule Formation during Infection and Sequesters Stress Granule Proteins within Viral Inclusions. AB - A hallmark of Ebola virus (EBOV) infection is the formation of viral inclusions in the cytoplasm of infected cells. These viral inclusions contain the EBOV nucleocapsids and are sites of viral replication and nucleocapsid maturation. Although there is growing evidence that viral inclusions create a protected environment that fosters EBOV replication, little is known about their role in the host response to infection. The cellular stress response is an effective antiviral strategy that leads to stress granule (SG) formation and translational arrest mediated by the phosphorylation of a translation initiation factor, the alpha subunit of eukaryotic initiation factor 2 (eIF2alpha). Here, we show that selected SG proteins are sequestered within EBOV inclusions, where they form distinct granules that colocalize with viral RNA. These inclusion-bound (IB) granules are functionally and structurally different from canonical SGs. Formation of IB granules does not indicate translational arrest in the infected cells. We further show that EBOV does not induce formation of canonical SGs or eIF2alpha phosphorylation at any time postinfection but is unable to fully inhibit SG formation induced by different exogenous stressors, including sodium arsenite, heat, and hippuristanol. Despite the sequestration of SG marker proteins into IB granules, canonical SGs are unable to form within inclusions, which we propose might be mediated by a novel function of VP35, which disrupts SG formation. This function is independent of VP35's RNA binding activity. Further studies aim to reveal the mechanism for SG protein sequestration and precise function within inclusions. IMPORTANCE: Although progress has been made developing antiviral therapeutics and vaccines against the highly pathogenic Ebola virus (EBOV), the cellular mechanisms involved in EBOV infection are still largely unknown. To better understand these intracellular events, we investigated the cellular stress response, an antiviral pathway manipulated by many viruses. We show that EBOV does not induce formation of stress granules (SGs) in infected cells and is therefore unrestricted by their concomitant translational arrest. We identified SG proteins sequestered within viral inclusions, which did not impair protein translation. We further show that EBOV is unable to block SG formation triggered by exogenous stress early in infection. These findings provide insight into potential targets of therapeutic intervention. Additionally, we identified a novel function of the interferon antagonist VP35, which is able to disrupt SG formation. PMID- 27252531 TI - Using the E4orf6-Based E3 Ubiquitin Ligase as a Tool To Analyze the Evolution of Adenoviruses. AB - E4orf6 proteins from all human adenoviruses form Cullin-based ubiquitin ligase complexes that, in association with E1B55K, target cellular proteins for degradation. While most are assembled with Cul5, a few utilize Cul2. BC-box motifs enable all these E4orf6 proteins to assemble ligase complexes with Elongins B and C. We also identified a Cul2-box motif used for Cul2 selection in all Cul2-based complexes. With this information, we set out to determine if other adenoviruses also possess the ability to form the ligase complex and, if so, to predict their Cullin usage. Here we report that all adenoviruses known to encode an E4orf6-like protein (mastadenoviruses and atadenoviruses) maintain the potential to form the ligase complex. We could accurately predict Cullin usage for E4orf6 products of mastadenoviruses and all but one atadenovirus. Interestingly, in nonhuman primate adenoviruses, we found a clear segregation of Cullin binding, with Cul5 utilized by viruses infecting great apes and Cul2 by Old/New World monkey viruses, suggesting that a switch from Cul2 to Cul5 binding occurred during the period when great apes diverged from monkeys. Based on the analysis of Cullin selection, we also suggest that the majority of human adenoviruses, which exhibit a broader tropism for the eye and the respiratory tract, exhibit Cul5 specificity and resemble viruses infecting great apes, whereas those that infect the gastrointestinal tract may have originated from monkey viruses that share Cul2 specificity. Finally, aviadenoviruses also appear to contain E4orf6 genes that encode proteins with a conserved XCXC motif followed by, in most cases, a BC-box motif. IMPORTANCE: Two early adenoviral proteins, E4orf6 and E1B55K, form a ubiquitin ligase complex with cellular proteins to ubiquitinate specific substrates, leading to their degradation by the proteasome. In studies with representatives of each human adenovirus species, we (and others) previously discovered that some viruses use Cul2 to form the complex, while others use Cul5. In the present study, we expanded our analyses to all sequenced adenoviruses and found that E4orf6 genes from all mast- and atadenoviruses encode proteins containing the motifs necessary to form the ligase complex. We found a clear separation in Cullin specificity between adenoviruses of great apes and Old/New World monkeys, lending support for a monkey origin for human viruses of the Human mastadenovirus A, F, and G species. We also identified previously unrecognized E4orf6 genes in the aviadenoviruses that encode proteins containing motifs permitting formation of the ubiquitin ligase. PMID- 27252532 TI - Suppression of IRG-1 Reduces Inflammatory Cell Infiltration and Lung Injury in Respiratory Syncytial Virus Infection by Reducing Production of Reactive Oxygen Species. AB - Respiratory syncytial virus (RSV) infection is a common cause of lower respiratory tract illness in infants and children. RSV is a negative-sense, single-strand RNA (ssRNA) virus that mainly infects airway epithelial cells. Accumulating evidence indicates that reactive oxygen species (ROS) production is a major factor for pulmonary inflammation and tissue damage of RSV disease. We investigated immune-responsive gene-1 (IRG1) expression during RSV infection, since IRG1 has been shown to mediate innate immune response to intracellular bacterial pathogens by modulating ROS and itaconic acid production. We found that RSV infection induced IRG1 expression in human A549 cells and in the lung tissues of RSV-infected mice. RSV infection or IRG1 overexpression promoted ROS production. Accordingly, knockdown of IRG1 induction blocked RSV-induced ROS production and proinflammatory cytokine gene expression. Finally, we showed that suppression of IRG1 induction reduced immune cell infiltration and prevented lung injury in RSV-infected mice. These results therefore link IRG1 induction to ROS production and immune lung injury after RSV infection. IMPORTANCE: RSV infection is among the most common causes of childhood diseases. Recent studies identify ROS production as a factor contributing to RSV disease. We investigated the cause of ROS production and identified IRG1 as a critical factor linking ROS production to immune lung injury after RSV infection. We found that IRG1 was induced in A549 alveolar epithelial cells and in mouse lungs after RSV infection. Importantly, suppression of IRG1 induction reduced inflammatory cell infiltration and lung injury in mice. This study links IRG1 induction to oxidative damage and RSV disease. It also uncovers a potential therapeutic target in reducing RSV-caused lung injury. PMID- 27252533 TI - Two Polypyrimidine Tracts in Intron 4 of the Major Immediate Early Gene Are Critical for Gene Expression Switching from IE1 to IE2 and for Replication of Human Cytomegalovirus. AB - The human cytomegalovirus (HCMV) major immediate early (MIE) gene is essential for viral replication. The most abundant products encoded by the MIE gene include IE1 and IE2. Genes of IE1 and IE2 share the MIE promoter (MIEP), the first 3 exons, and the first 2 introns. IE1 is expressed earlier than IE2 after CMV infection or MIE gene transfection. In this study, we identified 2 polypyrimidine (Py) tracts in intron 4 (between exons 4 and 5) that are responsible for transcriptional switching from IE1 to IE2. The first Py is important and the second one is essential for the splicing and expression of IE2. In searching for the mechanisms of MIE gene switching from IE1 to IE2, we found that the second Py was required for the IE2's fourth intron to bind to a splicing factor such as U2AF65, as determined by an RNA electrophoretic mobility shift assay and a chromatin immunoprecipitation (ChIP) assay, while the first Py enhanced the binding of U2AF65 with the intron. An HCMV BACmid with the second Py mutated failed to produce any virus, while the HCMV with the first Py mutated replicated with a defective phenotype. Furthermore, we designed a small RNA (scRNAPy) that is complementary to the intron RNA covering the two Pys. The scRNAPy interfered with the interaction of U2AF65 with the intron and repressed the IE2 expression. Therefore, our studies implied that IE2 gene splicing might be an anti-CMV target. IMPORTANCE: CMV is a ubiquitous herpesvirus and a significant cause of disease and death in the immunocompromised and elderly. Insights into its gene regulation will provide clues in designing anti-CMV strategies. The MIE gene is one of the earliest genes of CMV and is essential for CMV replication. It is known that the MIE gene needs to be spliced to produce more than two proteins; however, how MIE gene splicing is regulated remains elusive. In the present studies, we identified two Pys in intron 4 and found that the first Py is important and the second is required for the splicing and expression of IE2. We further investigated the mechanisms of gene switching from IE1 to IE2 and found that the two Pys are responsible for U2AF65's binding with intron 4. Therefore, the Pys in intron 4 are the cis elements that determine the fate of IE2 splicing. Furthermore, we found that a small RNA that is complementary to intron 4 repressed IE2 expression. Hence, we provide the first piece of evidence for a unique mechanism of MIE gene regulation at the splicing level. PMID- 27252534 TI - Identification and Characterization of Influenza Virus Entry Inhibitors through Dual Myxovirus High-Throughput Screening. AB - Influenza A virus (IAV) infections cause major morbidity and mortality, generating an urgent need for novel antiviral therapeutics. We recently established a dual myxovirus high-throughput screening protocol that combines a fully replication-competent IAV-WSN strain and a respiratory syncytial virus reporter strain for the simultaneous identification of IAV-specific, paramyxovirus-specific, and broad-spectrum inhibitors. In the present study, this protocol was applied to a screening campaign to assess a diverse chemical library with over 142,000 entries. Focusing on IAV-specific hits, we obtained a hit rate of 0.03% after cytotoxicity testing and counterscreening. Three chemically distinct hit classes with nanomolar potency and favorable cytotoxicity profiles were selected. Time-of-addition, minigenome, and viral entry studies demonstrated that these classes block hemagglutinin (HA)-mediated membrane fusion. Antiviral activity extends to an isolate from the 2009 pandemic and, in one case, another group 1 subtype. Target identification through biolayer interferometry confirmed binding of all hit compounds to HA. Resistance profiling revealed two distinct escape mechanisms: primary resistance, associated with reduced compound binding, and secondary resistance, associated with unaltered binding. Secondary resistance was mediated, unusually, through two different pairs of cooperative mutations, each combining a mutation eliminating the membrane-proximal stalk N-glycan with a membrane-distal change in HA1 or HA2. Chemical synthesis of an analog library combined with in silico docking extracted a docking pose for the hit classes. Chemical interrogation spotlights IAV HA as a major druggable target for small molecule inhibition. Our study identifies novel chemical scaffolds with high developmental potential, outlines diverse routes of IAV escape from entry inhibition, and establishes a path toward structure-aided lead development. IMPORTANCE: This study is one of the first to apply a fully replication-competent third-generation IAV reporter strain to a large-scale high-throughput screen (HTS) drug discovery campaign, allowing multicycle infection and screening in physiologically relevant human respiratory cells. A large number of potential druggable targets was thus chemically interrogated, but mechanistic characterization, positive target identification, and resistance profiling demonstrated that three chemically promising and structurally distinct hit classes selected for further analysis all block HA-mediated membrane fusion. Viral escape from inhibition could be achieved through primary and secondary resistance mechanisms. In silico docking predicted compound binding to a microdomain located at the membrane-distal site of the prefusion HA stalk that was also previously suggested as a target site for chemically unrelated HA inhibitors. This study identifies an unexpected chemodominance of the HA stalk microdomain for small-molecule inhibitors in IAV inhibitor screening campaigns and highlights a novel mechanism of cooperative resistance to IAV entry blockers. PMID- 27252535 TI - Vaccine-Elicited Mucosal and Systemic Antibody Responses Are Associated with Reduced Simian Immunodeficiency Viremia in Infant Rhesus Macaques. AB - Despite significant progress in reducing peripartum mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) with antiretroviral therapy (ART), continued access to ART throughout the breastfeeding period is still a limiting factor, and breast milk exposure to HIV accounts for up to 44% of MTCT. As abstinence from breastfeeding is not recommended, alternative means are needed to prevent MTCT of HIV. We have previously shown that oral vaccination at birth with live attenuated Mycobacterium tuberculosis strains expressing simian immunodeficiency virus (SIV) genes safely induces persistent SIV-specific cellular and humoral immune responses both systemically and at the oral and intestinal mucosa. Here, we tested the ability of oral M. tuberculosis vaccine strains expressing SIV Env and Gag proteins, followed by systemic heterologous (MVA-SIV Env/Gag/Pol) boosting, to protect neonatal macaques against oral SIV challenge. While vaccination did not protect infant macaques against oral SIV acquisition, a subset of immunized animals had significantly lower peak viremia which inversely correlated with prechallenge SIV Env-specific salivary and intestinal IgA responses and higher-avidity SIV Env-specific IgG in plasma. These controller animals also maintained CD4(+) T cell populations better and showed reduced tissue pathology compared to noncontroller animals. We show that infants vaccinated at birth can develop vaccine-induced SIV-specific IgA and IgG antibodies and cellular immune responses within weeks of life. Our data further suggest that affinity maturation of vaccine-induced plasma antibodies and induction of mucosal IgA responses at potential SIV entry sites are associated with better control of viral replication, thereby likely reducing SIV morbidity. IMPORTANCE: Despite significant progress in reducing peripartum MTCT of HIV with ART, continued access to ART throughout the breastfeeding period is still a limiting factor. Breast milk exposure to HIV accounts for up to 44% of MTCT. Alternative measures, in addition to ART, are needed to achieve the goal of an AIDS-free generation. Pediatric HIV vaccines constitute a core component of such efforts. The results of our pediatric vaccine study highlight the potential importance of vaccine-elicited mucosal Env-specific IgA responses in combination with high-avidity systemic Env-specific IgG in protection against oral SIV transmission and control of viral replication in infant macaques. The induction of potent mucosal IgA antibodies by our vaccine is remarkable considering the age dependent development of mucosal IgA responses postbirth. A deeper understanding of postnatal immune development may inform the design of improved vaccine strategies to enhance systemic and mucosal SIV/HIV antibody responses. PMID- 27252536 TI - Herpes Simplex Virus Capsid Localization to ESCRT-VPS4 Complexes in the Presence and Absence of the Large Tegument Protein UL36p. AB - UL36p (VP1/2) is the largest protein encoded by herpes simplex virus 1 (HSV-1) and resides in the innermost layer of tegument, the complex protein layer between the capsid and envelope. UL36p performs multiple functions in the HSV life cycle, including a critical but unknown role in capsid cytoplasmic envelopment. We tested whether UL36p is essential for envelopment because it is required to engage capsids with the cellular ESCRT/Vps4 apparatus. A green fluorescent protein (GFP)-fused form of the dominant negative ATPase Vps4-EQ was used to irreversibly tag ESCRT envelopment sites during infection by UL36p-expressing and UL36-null HSV strains. Using fluorescence microscopy and scanning electron microscopy, we quantitated capsid/Vps4-EQ colocalization and examined the ultrastructure of the corresponding viral assembly intermediates. We found that loss of UL36p resulted in a two-thirds reduction in the efficiency of capsid/Vps4 EQ association but that the remaining UL36p-null capsids were still able to engage the ESCRT envelopment apparatus. It appears that although UL36p helps to couple HSV capsids to the ESCRT pathway, this is likely not the sole reason for its absolute requirement for envelopment. IMPORTANCE: Envelopment of the HSV capsid is essential for the assembly of an infectious virion and requires the complex interplay of a large number of viral and cellular proteins. Critical to envelope assembly is the virally encoded protein UL36p, whose function is unknown. Here we test the hypothesis that UL36p is essential for the recruitment of cellular ESCRT complexes, which are also known to be required for envelopment. PMID- 27252537 TI - Phosphorylation of Human Metapneumovirus M2-1 Protein Upregulates Viral Replication and Pathogenesis. AB - Human metapneumovirus (hMPV) is a major causative agent of upper- and lower respiratory-tract infections in infants, the elderly, and immunocompromised individuals worldwide. Like all pneumoviruses, hMPV encodes the zinc binding protein M2-1, which plays important regulatory roles in RNA synthesis. The M2-1 protein is phosphorylated, but the specific role(s) of the phosphorylation in viral replication and pathogenesis remains unknown. In this study, we found that hMPV M2-1 is phosphorylated at amino acid residues S57 and S60. Subsequent mutagenesis found that phosphorylation is not essential for zinc binding activity and oligomerization, whereas inhibition of zinc binding activity abolished the phosphorylation and oligomerization of the M2-1 protein. Using a reverse genetics system, recombinant hMPVs (rhMPVs) lacking either one or both phosphorylation sites in the M2-1 protein were recovered. These recombinant viruses had a significant decrease in both genomic RNA replication and mRNA transcription. In addition, these recombinant viruses were highly attenuated in cell culture and cotton rats. Importantly, rhMPVs lacking phosphorylation in the M2-1 protein triggered high levels of neutralizing antibody and provided complete protection against challenge with wild-type hMPV. Collectively, these data demonstrated that phosphorylation of the M2-1 protein upregulates hMPV RNA synthesis, replication, and pathogenesis in vivo IMPORTANCE: The pneumoviruses include many important human and animal pathogens, such as human respiratory syncytial virus (hRSV), hMPV, bovine RSV, and avian metapneumovirus (aMPV). Among these viruses, hRSV and hMPV are the leading causes of acute respiratory tract infection in infants and children. Currently, there is no antiviral or vaccine to combat these diseases. All known pneumoviruses encode a zinc binding protein, M2-1, which is a transcriptional antitermination factor. In this work, we found that phosphorylation of M2-1 is essential for virus replication and pathogenesis in vivo Recombinant hMPVs lacking phosphorylation in M2-1 exhibited limited replication in the upper and lower respiratory tract and triggered strong protective immunity in cotton rats. This work highlights the important role of M2 1 phosphorylation in viral replication and that inhibition of M2-1 phosphorylation may serve as a novel approach to develop live attenuated vaccines as well as antiviral drugs for pneumoviruses. PMID- 27252538 TI - Human T-Lymphotropic Virus Type 1-Induced Overexpression of Activated Leukocyte Cell Adhesion Molecule (ALCAM) Facilitates Trafficking of Infected Lymphocytes through the Blood-Brain Barrier. AB - Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease develops upon infiltration of HTLV-1 infected lymphocytes into the central nervous system, mostly the thoracic spinal cord. The central nervous system is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. In this study, we investigated the role of activated leukocyte cell adhesion molecule (ALCAM/CD166), a member of the immunoglobulin superfamily, in the crossing of the BBB by HTLV-1-infected lymphocytes. We demonstrated that ALCAM is overexpressed on the surface of HTLV-1 infected lymphocytes, both in chronically infected cell lines and in primary infected CD4(+) T lymphocytes. ALCAM overexpression results from the activation of the canonical NF-kappaB pathway by the viral transactivator Tax. In contrast, staining of spinal cord sections of HAM/TSP patients showed that ALCAM expression is not altered on the BBB endothelium in the context of HTLV-1 infection. ALCAM blockade or downregulation of ALCAM levels significantly reduced the migration of HTLV-1-infected lymphocytes across a monolayer of human BBB endothelial cells. This study suggests a potential role for ALCAM in HAM/TSP pathogenesis. IMPORTANCE: Human T-lymphotropic virus type 1 (HTLV-1) is the etiological agent of a slowly progressive neurodegenerative disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This disease is the consequence of the infiltration of HTLV-1-infected lymphocytes into the central nervous system (CNS), mostly the thoracic spinal cord. The CNS is normally protected by a physiological structure called the blood-brain barrier (BBB), which consists primarily of a continuous endothelium with tight junctions. The mechanism of migration of lymphocytes into the CNS is unclear. Here, we show that the viral transactivator Tax increases activated leukocyte cell adhesion molecule (ALCAM/CD166) expression. This molecule facilitates the migration of lymphocytes across the BBB endothelium. Targeting this molecule could be of interest in preventing or reducing the development of HAM/TSP. PMID- 27252545 TI - A CO2-Free Synthetic Host-Odor Mixture That Attracts and Captures Triatomines: Effect of Emitted Odorant Ratios. AB - Triatomines, vectors of Chagas Disease, are hematophagous insects. Efforts have been made to develop synthetic attractants based on vertebrate odor-to lure them into traps. However, because those lures are not practical or have low capture efficiency, they are not in use in control programs. Therefore, more work is needed to reach a practical and efficient odor lure. Recently, a three-component, CO2-free, synthetic blend of vertebrate odor (consisting of ammonia, l-(+)-lactic acid, and hexanoic acid), known as Sweetscent (Biogents AG, Regensburg, Germany), was shown to attract and capture triatomines in the laboratory. In this study, using a trap olfactometer and an odor blend with constituents similar to those of Sweetscent (delivered from low-density polyethylene sachets) we found that the odorant ratios of the mixtures have a strong effect in the capture of triatomines. The blend with the most efficient combination of odorant ratios evoked ca. 81% capture in two relevant triatomine species. In the case of the most effective odor mixtures, we measured the odor mass emission for the three components of the mixture and therefore were able to estimate the odorant ratios emitted that were responsible for such a high capture performance. Thus, in those mixtures, pentanoic acid was the main component (ca. 65 %) followed by ammonia (ca. 28%) and, l(+)-lactic acid (ca. 7 %). Our results are encouraging as efficient, practical, and cheap odor baits to trap triatomines in the field would be within reach. The odor-delivery system used should be improved to increase stability of odor emission. PMID- 27252540 TI - Embryonic hematopoiesis in vertebrate somites gives rise to definitive hematopoietic stem cells. AB - Hematopoietic stem cells (HSCs) replenish all types of blood cells. It is debating whether HSCs in adults solely originate from the aorta-gonad-mesonephros (AGM) region, more specifically, the dorsal aorta, during embryogenesis. Here, we report that somite hematopoiesis, a previously unwitnessed hematopoiesis, can generate definitive HSCs (dHSCs) in zebrafish. By transgenic lineage tracing, we found that a subset of cells within the forming somites emigrate ventromedially and mix with lateral plate mesoderm-derived primitive hematopoietic cells before the blood circulation starts. These somite-derived hematopoietic precursors and stem cells (sHPSCs) subsequently enter the circulation and colonize the kidney of larvae and adults. RNA-seq analysis reveals that sHPSCs express hematopoietic genes with sustained expression of many muscle/skeletal genes. Embryonic sHPSCs transplanted into wild-type embryos expand during growth and survive for life time with differentiation into various hematopoietic lineages, indicating self renewal and multipotency features. Therefore, the embryonic origin of dHSCs in adults is not restricted to the AGM. PMID- 27252539 TI - Dengue Virus Subverts Host Innate Immunity by Targeting Adaptor Protein MAVS. AB - Dengue virus (DENV) is the most common mosquito-borne virus infecting humans and is currently a serious global health challenge. To establish infection in its host cells, DENV must subvert the production and/or antiviral effects of interferon (IFN). The aim of this study was to understand the mechanisms by which DENV suppresses IFN production. We determined that DENV NS4A interacts with mitochondrial antiviral signaling protein (MAVS), which was previously found to activate NF-kappaB and IFN regulatory factor 3 (IRF3), thus inducing type I IFN in the mitochondrion-associated endoplasmic reticulum membranes (MAMs). We further demonstrated that NS4A is associated with the N-terminal CARD-like (CL) domain and the C-terminal transmembrane (TM) domain of MAVS. This association prevented the binding of MAVS to RIG-I, resulting in the repression of RIG-I induced IRF3 activation and, consequently, the abrogation of IFN production. Collectively, our findings illustrate a new molecular mechanism by which DENV evades the host immune system and suggest new targets for anti-DENV strategies. IMPORTANCE: Type I interferon (IFN) constitutes the first line of host defense against invading viruses. To successfully establish infection, dengue virus (DENV) must counteract either the production or the function of IFN. The mechanism by which DENV suppresses IFN production is poorly understood and characterized. In this study, we demonstrate that the DENV NS4A protein plays an important role in suppressing interferon production through binding MAVS and disrupting the RIG-I-MAVS interaction in mitochondrion-associated endoplasmic reticulum membranes (MAMs). Our study reveals that MAVS is a novel host target of NS4A and provides a molecular mechanism for DENV evasion of the host innate immune response. These findings have important implications for understanding the pathogenesis of DENV and may provide new insights into using NS4A as a therapeutic and/or prevention target. PMID- 27252546 TI - The Critical Reader-Magnitude and Strength of Findings. PMID- 27252547 TI - The Vertical Drop Jump Is a Poor Screening Test for ACL Injuries: Letter to the Editor. PMID- 27252548 TI - The Vertical Drop Jump Is a Poor Screening Test for ACL Injuries: Response. PMID- 27252549 TI - Screening Tests for ACL Injury: Letter to the Editor. PMID- 27252550 TI - Screening Tests for ACL Injury: Response. PMID- 27252551 TI - Collegiate Rugby Has Lower Injury Incidence Than American Football: Letter to the Editor. PMID- 27252552 TI - Collegiate Rugby Has Lower Injury Incidence Than American Football: Response. PMID- 27252553 TI - Sex-Based Differences as a Predictor of Recovery Trajectories in Young Athletes After a Sports-Related Concussion: Letter to the Editor. PMID- 27252554 TI - Sex-Based Differences as a Predictor of Recovery Trajectories in Young Athletes After a Sports-Related Concussion: Response. PMID- 27252555 TI - A Message from the Editor. PMID- 27252556 TI - A Promise Fulfilled-Addressing the Nation's Opioid Crisis Collectively. PMID- 27252557 TI - NIS vs. Immunization Registry MMR Rates for Counties in Oregon. PMID- 27252559 TI - Assessing Clinical Research Capacity in Vietnam: A Framework for Strengthening Capability for Clinical Trials in Developing Countries. AB - Although improving health systems promises important benefits, most developing nations lack the resources to support nationally driven clinical research. Strengthened clinical research capacity can advance national health goals by supporting greater autonomy in aligning research with national priorities. From March through June 2010, we assessed six elements of clinical research capacity in Vietnam: research agenda; clinical investigators and biostatisticians; donors and sponsors; community involvement; scientific, ethical, safety, and quality oversight; and clinical research institutions. Assessments were drawn from interviews with investigators, Ministry of Health staff members, nongovernment organizations, and U.S. Mission staff members, and document review. Observations and recommendations were shared with collaborators. Reassessment in 2015 found growth in the number of clinical trials, improved regulation in human subjects protection and community engagement, and modest advances in research agenda setting. Training and investment in institutions remain challenging. A framework for assessing clinical research capacity can affirm strengths and weaknesses and guide the coordination of capacity-building efforts. PMID- 27252558 TI - Understanding Non-Completion of the Human Papillomavirus Vaccine Series: Parent Reported Reasons for Why Adolescents Might Not Receive Additional Doses, United States, 2012. AB - Completion rates of the human papillomavirus (HPV) vaccine series among U.S. adolescents are below public health targets. We explored parent-reported reasons for their children's non-completion of the HPV vaccine series using a nationally representative online survey of parents of children aged 9-17 years, fielded in October 2012. Among the 1,653 parents who responded, the proportion reporting that their child would definitely continue with the HPV vaccine series among those who had started the series ranged from 28% to 54%. The most common reason cited by parents for non-completion of the series was their child's fear of needles, followed by lack of awareness about additional doses and safety concerns. These findings demonstrate the need to encourage adoption of strategies addressing needle fears, utilize reminders for parents about subsequent doses, and emphasize recent HPV vaccine safety data in discussions with parents. PMID- 27252560 TI - Using Hospital Inpatient Discharge Data to Supplement Active Surveillance for Invasive Pneumococcal Disease: Is the Extract Worth the Exertion? AB - OBJECTIVE: Invasive pneumococcal disease (IPD) surveillance systems monitor morbidity, mortality, and vaccine impact; accurate surveillance is important to detect changes in epidemiology. We evaluated completeness of IPD reporting in New Mexico by comparing data from the Hospital Inpatient Discharge Database (HIDD) and the New Mexico Active Bacterial Core Surveillance (ABCs) program. METHODS: We linked data from the HIDD and the ABCs program. We defined cases of IPD in the HIDD among New Mexico residents with hospitalizations during 2007-2009 as specific (320.1 or 038.2) or nonspecific (481, 320.2, or 041.2) using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. To validate if HIDD records that could not be matched to ABCs data were true IPD cases, we reviewed laboratory data and determined if Streptococcus pneumoniae (S. pneumoniae) had been isolated from a sterile body site. RESULTS: We examined 732 HIDD records for cases that were not matched in the ABCs database; of such records, S. pneumoniae was isolated from a sterile body site in 10 HIDD records. CONCLUSION: ABCs data detected the majority of IPD cases in New Mexico. Laboratory and medical record review is essential when using HIDD data because ICD-9-CM coding alone does not ensure data accuracy. The addition of IPD cases to the ABCs program from the HIDD was minimally beneficial to active surveillance and reporting completeness in New Mexico. States that rely exclusively on passive reporting and that have access to HIDD data might use linkages of pneumococcal and IPD-specific ICD-9-CM-coded HIDD data to improve IPD surveillance and case ascertainment. PMID- 27252561 TI - Dependency on Smartphone Use and Its Association with Anxiety in Korea. AB - OBJECTIVE: South Korea has the highest rate of smartphone ownership worldwide, which is a potential concern given that smartphone dependency may have deleterious effects on health. We investigated the relationship between smartphone dependency and anxiety. METHODS: Participants included 1,236 smartphone-using students (725 men and 511 women) from six universities in Suwon, South Korea. Participants completed measures of smartphone use, smartphone dependency, anxiety, and general characteristics (i.e., demographic, health related, and socioeconomic characteristics). To measure smartphone dependency and anxiety, we used questionnaires of Yang's test developed from Young's Internet Addiction Test and Zung's Self-Rating Anxiety Scale. We used multiple logistic regression to determine the association between smartphone dependency and anxiety after adjusting for relevant factors. RESULTS: On a scale from 25 to 100, with higher scores on the smartphone dependency test indicating greater dependency, women were significantly more dependent on smartphones than were men (mean smartphone dependency score: 50.7 vs. 56.0 for men and women, respectively, p<0.001). However, the amount of time spent using smartphones and the purpose of smartphone use affected smartphone dependency in both men and women. Particularly, when daily use time increased, smartphone dependency showed an increasing trend. Compared with times of use <2 hours vs. >=6 hours, men scored 46.2 and 56.0 on the smartphone dependency test, while women scored 48.0 and 60.4, respectively (p<0.001). Finally, for both men and women, increases in smartphone dependency were associated with increased anxiety scores. With each one-point increase in smartphone dependency score, the risk of abnormal anxiety in men and women increased by 10.1% and 9.2%, respectively (p<0.001). CONCLUSION: Among this group of university students in South Korea, smartphone dependency appeared to be associated with increased anxiety. Standards for smartphone use might help prevent deleterious health effects. PMID- 27252562 TI - Performance of Self-Report to Establish Cancer Diagnoses in Disaster Responders and Survivors, World Trade Center Health Registry, New York, 2001-2007. AB - OBJECTIVE: Large-scale disasters may disrupt health surveillance systems, depriving health officials and researchers of timely and accurate information needed to assess disaster-related health effects and leading to use of less reliable self-reports of health outcomes. In particular, ascertainment of cancer in a population is ordinarily obtained through linkage of self-reported data with regional cancer registries, but exclusive reliance on these sources following a disaster may result in lengthy delays or loss of critical data. To assess the impact of such reliance, we validated self-reported cancer in a cohort of 59,340 responders and survivors of the World Trade Center disaster against data from 11 state cancer registries (SCRs). METHODS: We focused on residents of the 11 states with SCRs and on cancers diagnosed from September 11, 2001, to the date of their last survey participation. Medical records were also sought in a subset of 595 self-reported cancer patients who were not recorded in an SCR. RESULTS: Overall sensitivity and specificity of self-reported cancer were 83.9% (95% confidence interval [CI] 81.9, 85.9) and 98.5% (95% CI 98.4, 98.6), respectively. Site specific sensitivities were highest for pancreatic (90.9%) and testicular (82.4%) cancers and multiple myeloma (84.6%). Compared with enrollees with true-positive reports, enrollees with false-negative reports were more likely to be non Hispanic black (adjusted odds ratio [aOR] = 1.8, 95% CI 1.2, 2.9) or Asian (aOR=2.2, 95% CI 1.2, 4.1). Among the 595 cases not recorded in an SCR, 13 of 62 (21%) cases confirmed through medical records were reportable to SCRs. CONCLUSION: Self-report of cancer had relatively high sensitivity among adults exposed to the World Trade Center disaster, suggesting that self-reports of other disaster-related conditions less amenable to external validation may also be reasonably valid. PMID- 27252563 TI - Barriers to Treatment Among New York City Residents with Chronic Hepatitis C Virus Infection, 2014. AB - OBJECTIVE: New, highly effective hepatitis C virus (HCV) medications recently changed the landscape of HCV treatment. Access to treatment, however, is limited. The New York City Department of Health and Mental Hygiene conducted an enhanced surveillance project to better understand the reasons patients are not treated for HCV. METHODS: In June 2014, we randomly selected 300 adults who were reported through routine surveillance as having a positive HCV ribonucleic acid test result and who had seen a medical provider since June 2012. We collected information on demographics, treatment, and barriers to treatment from these 300 patients and their providers by telephone, fax, mail, and medical record review. RESULTS: Of 179 providers, 74 (41%) cited co-occurring conditions and 50 (28%) cited patients not keeping follow-up or referral appointments with specialists as common barriers to treatment. Forty providers (22%) reported that they do not prescribe HCV medications and instead refer patients to specialists for treatment. Of 89 patients citing barriers to treatment, 30 (34%) cited co occurring conditions, 26 (29%) cited concerns about side effects, 21 (24%) indicated not feeling sick, 15 (17%) cited waiting for a better treatment regimen, and 12 (13%) cited medication costs or insurance issues. Only 11 providers and 10 patients denied any barriers to treatment. CONCLUSION: Increasing the number of New York City residents with HCV infection who are treated and cured will require programs to increase provider capacity, change provider behavior in treating patients with substance use and medical conditions, improve patient awareness of new medications, provide patient navigation and care coordination support through treatment, and initiate advocacy and policy work. PMID- 27252564 TI - County Health Factors Associated with Avoidable Deaths from Cardiovascular Disease in the United States, 2006-2010. AB - OBJECTIVE: Many cardiovascular deaths can be avoided through primary prevention to address cardiovascular disease (CVD) risk factors or better access to quality medical care. In this cross-sectional study, we examined the relationship between four county-level health factors and rates of avoidable death from CVD during 2006-2010. METHODS: We defined avoidable deaths from CVD as deaths among U.S. residents younger than 75 years of age caused by the following underlying conditions, using International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes: ischemic heart disease (I20-I25), chronic rheumatic heart disease (I05-I09), hypertensive disease (I10-I15), or cerebrovascular disease (I60-I69). We stratified county-level death rates by race (non-Hispanic white or non-Hispanic black) and age-standardized them to the 2000 U.S. standard population. We used County Health Rankings data to rank county level z scores corresponding to four health factors: health behavior, clinical care, social and economic factors, and physical environment. We used Poisson rate ratios (RRs) and 95% confidence intervals (CIs) to compare rates of avoidable death from CVD by health-factor quartile. RESULTS: In a comparison of worst ranked and best-ranked counties, social and economic factors had the strongest association with rates of avoidable death per 100,000 population from CVD for the total population (RR=1.49; 95% CI 1.39, 1.60) and for each racial/ethnic group (non-Hispanic white: RR=1.37; 95% CI 1.29, 1.45; non-Hispanic black: RR=1.54; 95% CI 1.42, 1.67). Among the non-Hispanic white population, health behaviors had the next strongest association, followed by clinical care. Among the non-Hispanic black population, we observed a significant association with clinical care and physical environment in a comparison of worst-ranked and best-ranked counties. CONCLUSION: Social and economic factors have the strongest association with rates of avoidable death from CVD by county, which reinforces the importance of social and economic interventions to address geographic disparities in avoidable deaths from CVD. PMID- 27252565 TI - A Review of State Licensing Regulations to Determine Alignment with Best Practices to Prevent Human Norovirus Infections in Child-Care Centers. AB - OBJECTIVES: Close, frequent contact between children and care providers in child care centers presents many opportunities to spread human noroviruses. We compared state licensing regulations for child-care centers with national guidelines written to prevent human noroviruses. METHODS: We reviewed child-care licensing regulations for all 50 U.S. states and the District of Columbia in effect in June 2015 to determine if these regulations fully, partially, or did not address 14 prevention practices in four topic areas: (1) hand hygiene, (2) exclusion of ill people, (3) environmental sanitation, and (4) diapering. RESULTS: Approximately two-thirds (8.9) of the 14 practices across all state regulations were partially or fully addressed, with few (2.6) fully addressed. Practices related to exclusion of ill people and diapering were fully addressed most often, while practices related to hand hygiene and environmental sanitation were fully addressed least often. CONCLUSION: Regulations based on guidelines for best practices are one way to prevent the spread of human noroviruses in child-care facilities, if the regulations are enforced. Our findings show that, in mid-2015, many state child-care regulations did not fully address these guidelines, suggesting the need to review these regulations to be sure they are based on best practices. PMID- 27252566 TI - Social Media's Initial Reaction to Information and Misinformation on Ebola, August 2014: Facts and Rumors. AB - OBJECTIVE: We analyzed misinformation about Ebola circulating on Twitter and Sina Weibo, the leading Chinese microblog platform, at the outset of the global response to the 2014-2015 Ebola epidemic to help public health agencies develop their social media communication strategies. METHODS: We retrieved Twitter and Sina Weibo data created within 24 hours of the World Health Organization announcement of a Public Health Emergency of International Concern (Batch 1 from August 8, 2014, 06:50:00 Greenwich Mean Time [GMT] to August 9, 2014, 06:49:59 GMT) and seven days later (Batch 2 from August 15, 2014, 06:50:00 GMT to August 16, 2014, 06:49:59 GMT). We obtained and analyzed a 1% random sample of tweets containing the keyword Ebola. We retrieved all Sina Weibo posts with Chinese keywords for Ebola for analysis. We analyzed changes in frequencies of keywords, hashtags, and Web links using relative risk (RR) and c(2) feature selection algorithm. We identified misinformation by manual coding and categorizing randomly selected sub-datasets. RESULTS: We identified two speculative treatments (i.e., bathing in or drinking saltwater and ingestion of Nano Silver, an experimental drug) in our analysis of changes in frequencies of keywords and hashtags. Saltwater was speculated to be protective against Ebola in Batch 1 tweets but their mentions decreased in Batch 2 (RR=0.11 for "salt" and RR=0.14 for "water"). Nano Silver mentions were higher in Batch 2 than in Batch 1 (RR=10.5). In our manually coded samples, Ebola-related misinformation constituted about 2% of Twitter and Sina Weibo content. A range of 36%-58% of the posts were news about the Ebola outbreak and 19%-24% of the posts were health information and responses to misinformation in both batches. In Batch 2, 43% of Chinese microblogs focused on the Chinese government sending medical assistance to Guinea. CONCLUSION: Misinformation about Ebola was circulated at a very low level globally in social media in either batch. Qualitative and quantitative analyses of social media posts can provide relevant information to public health agencies during emergency responses. PMID- 27252567 TI - Human Papillomavirus Vaccination in Washington State: Estimated Coverage and Missed Opportunities, 2006-2013. AB - OBJECTIVE: Human papillomavirus (HPV) causes almost all cervical cancer in women and contributes to vaginal, anal, oropharyngeal, and penile cancer morbidity and mortality. Although vaccines effective in preventing up to nine types of HPV are available, vaccination rates are low nationally. We assessed HPV vaccination coverage by age, sex, and county using Washington State Immunization Information System data. METHODS: We calculated on-time dose coverage by county and statewide among adolescents aged 11-12 years and assessed coverage by age 18 years. We calculated missed opportunities as the number of visits at which doses of other adolescent vaccines were administered without administration of the first dose of HPV vaccine (HPV1). RESULTS: In 2013, HPV vaccination coverage estimates with one, two, and three doses (HPV1-3) for adolescents aged 11-12 years were 48.5%, 32.4%, and 18.3% among girls and 31.2%, 17.1%, and 8.1% among boys. The three dose HPV vaccine coverage estimate increased to 40.1% among girls by age 18 but was unchanged for boys. Coverage estimates varied by age, sex, and county. One third of eligible unvaccinated girls and two of five eligible boys aged 11-17 years had at least one missed opportunity to receive HPV1. CONCLUSION: Despite a recommendation to vaccinate adolescents aged 11-12 years, HPV vaccination is often delayed and coverage levels among all age groups are below national target levels. Improved understanding of the variability of HPV vaccination coverage rates by age, sex, and county can inform targeted interventions statewide. PMID- 27252568 TI - Utility of Keywords from Chest Radiograph Reports for Pneumonia Surveillance Among Hospitalized Patients with Influenza: The CDC Influenza Hospitalization Surveillance Network, 2008-2009. AB - OBJECTIVE: Transcripts from admission chest radiographs could aid in identification of pneumonia cases for public health surveillance. We assessed the reliability of radiographic data abstraction and performance of radiographic key terms to identify pneumonia in patients hospitalized with laboratory-confirmed influenza virus infection. METHODS: We used data on patients hospitalized with laboratory-confirmed influenza virus infection from October 2008 through December 2009 from 10 geographically diverse U.S. study sites participating in the Influenza Hospitalization Surveillance Network (FluSurv-NET). Radiographic key terms (i.e., bronchopneumonia, consolidation, infiltrate, airspace density, and pleural effusion) were abstracted from final impressions of chest radiograph reports. We assessed the reliability of radiographic data abstraction by examining the percent agreement and Cohen's k statistic between clinicians and surveillance staff members. Using a composite reference standard for presence or absence of pneumonia based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and discharge summary data, we calculated sensitivity, specificity, positive predictive value (PPV), and percent agreement for individual and combined radiographic key terms. RESULTS: For each radiographic key term, the percent agreement between clinicians and surveillance staff members ranged from 89.4% to 98.6% and Cohen's k ranged from 0.46 (moderate) to 0.84 (almost perfect). The combination of bronchopneumonia or consolidation or infiltrate or airspace density terms had sensitivity of 66.5%, specificity of 89.2%, PPV of 80.4%, and percent agreement of 80.1%. Adding pleural effusion did not result in significant changes in sensitivity, specificity, PPV, or percent agreement. CONCLUSION: Radiographic key terms abstracted by surveillance staff members from final impressions of chest radiograph reports had moderate to almost perfect reliability and could be used to identify pneumonia among patients hospitalized with laboratory-confirmed influenza virus infection. This method can inform pneumonia surveillance and aid in public health response. PMID- 27252570 TI - Quarantine and Liability in the Context of Ebola. PMID- 27252569 TI - The Impact of Benzodiazepine Use on Mortality Among Polysubstance Users in Vancouver, Canada. AB - OBJECTIVE: Illicit drug use is a well-established risk factor for increased morbidity and mortality. However, little is known about the impact of benzodiazepine use on mortality among populations of polysubstance users. This study aimed to identify the effect of benzodiazepine use on mortality among a prospective cohort of people in Canada who inject drugs (PWID). METHODS: A cohort of PWID in Vancouver, Canada, was prospectively followed from May 1996 through November 2013. Data on participants were linked to the provincial vital statistics registry to ascertain mortality rates and causes of death. Multivariable extended Cox regression with time-dependent variables was used to investigate the relationship between benzodiazepine use and time to all-cause mortality. RESULTS: During the study period, 2,802 participants were followed for a median of 67 months (interquartile range: 25-107). In total, 527 (18.8%) participants died, for an incidence density of mortality of 2.9 (95% confidence interval [CI] 2.7, 3.2) deaths per 100 person-years. After adjusting for HIV infection and other potential confounders, benzodiazepine use was independently associated with increased all-cause mortality (adjusted hazard ratio = 1.86, 95% CI 1.38, 2.51) and had a higher risk for mortality than all other traditional substances of abuse among this population. Results were consistent when non overdose mortality was considered. CONCLUSION: In this setting, benzodiazepine use was more strongly associated with mortality than any other substance of abuse. Greater recognition of the safety concerns related to benzodiazepines and strategies to prevent diversion to illicit use are needed. PMID- 27252573 TI - A Mismatch Between the Educational Pipeline and Public Health Workforce: Can It Be Reconciled? PMID- 27252574 TI - Dan Vaughn's Legacy. PMID- 27252575 TI - Trigger point dry needling: the data do not support broad applicability or robust effect. PMID- 27252576 TI - Rebuttal to letter to the editor. PMID- 27252577 TI - EMG activity of selected rotator cuff musculature during grade III distraction and posterior glide glenohumeral mobilization: results of a pilot trial comparing painful and non-painful shoulders. AB - OBJECTIVES: The objectives of this pilot study were to investigate rotator cuff activity that may be present during grade III distraction and posterior glide mobilization of the glenohumeral (GH) joint, as well as to examine any differences in response between painful and non-painful shoulders utilizing these techniques. METHODS: EMG data were collected using Delsys EMGworks((r)) software and Trigno((r)) mini-wireless electrodes for the supraspinatus, infraspinatus and upper trapezius musculature during grade III GH distraction and posterior glide mobilization. A total of 20 shoulders (10 painful, 10 non-painful) were recruited from a sample of convenience. Submaximal voluntary dynamic contraction against gravity was used as reference for each of the three selected muscles. Participants underwent two trials of each mobilization, and the mean results for each group were assessed using descriptive statistics (mean, standard deviation) and effect size. RESULTS: Both the painful and non-painful groups exhibited considerable levels of rotator cuff activity during each test parameter, with the painful group consistently generating higher supraspinatus and infraspinatus RMS and peak force activity. Analysis of the peak combined rotator cuff activity during distraction (d = 0.58) and posterior glides (d = 0.64) suggests moderate to-high practical significance of the results. DISCUSSION: GH distraction and posterior glide mobilizations have traditionally been thought of as passive treatment procedures. The results of this pilot study indicate that the supraspinatus and infraspinatus are significantly active during these techniques. Findings suggest that during these techniques, the total infra/supraspinatus EMG activity approaches the level produced while raising the arm against gravity. LEVEL OF EVIDENCE: 2b. PMID- 27252578 TI - The effects of neurodynamic straight leg raise treatment duration on range of hip flexion and protective muscle activity at P1. AB - STUDY DESIGN: Randomized, single blind, same subject crossover trial. OBJECTIVES: To compare the effects of two neurodynamic treatment doses on range of hip flexion (ROM HF) and electromyographic (EMG) activity of semitendinosus, at first onset of pain (P1). METHODS: A total of 26 healthy participants without low back or leg pain received each treatment in a random order with at least 48 hours between sessions. Baseline ROM HF and EMG magnitude of semitendinosus at P1 were collected. Subjects then received either 361 or 362 minutes of oscillating end of range (grade IVz) straight leg raise (SLR) neurodynamic treatment and were re assessed for baseline measures. RESULTS: There was no significant difference between groups in EMG magnitude (P50.190) and ROM HF (P50.739) at P1. There was also no significant difference within groups in EMG magnitude at P1 (P50.182); however, there was a significant improvement in ROM HF at P1 in both groups compared to baseline readings (P50.000), with increases of 6.7u and 5.1u for the 361- and 362-minute groups, respectively. CONCLUSION: Findings indicate that 362 minutes of oscillating grade IVz SLR neurodynamic treatment has no additional benefit over 361 minute, on ROM HF or EMG magnitude of semitendinosus at P1. Using an oscillating SLR treatment may, however, help to increase pain-free ROM HF, although further studies are necessary to confirm this. PMID- 27252579 TI - The relationship between Quebec Task Force Classification and outcome in patients with low back pain treated through mechanical diagnosis and therapy. AB - OBJECTIVE: To determine the correlation between the Quebec Task Force Classification (QTFC) system and outcome in patients with non-specific low back pain (LBP). METHODS: Forty-nine patients who were treated in outpatient physical therapy clinics of Catholic Health System (CHS) of Western New York (WNY) were classified according to the QTFC at the initial examination by physical therapists (PTs) with training in Mechanical Diagnosis and Therapy (MDT). The patient's perceived level of function was assessed with the Focus On Therapeutic Outcomes (FOTO) tool at the initial examination, 2 weeks following the initiation of physical therapy and again at discharge. RESULTS: A linear regression model between acuity and change in FOTO score was performed and demonstrated statistical significance (P<0.05) as the more favorable outcome was found with the more acute patients. Spearman correlations between change in FOTO score and QTFC, duration of treatment and acuity of condition, and number of visits and change in FOTO score were not found to be statistically significant. CONCLUSIONS: The patients treated in this study demonstrated functional improvement in an average of eight visits, indicating efficacious care. Future research is needed to determine prioritized intervention strategies for designated LBP classifications. PMID- 27252580 TI - A novel way of functional retraining of cervical motor control in a water polo player with combined cervicogenic and tension type headaches. AB - This case report introduces an innovative and novel way of functionally retraining the sport specific cervical function in a 13-year-old elite water polo player with a combined tension type headache and cervicogenic headache. After an evidence based assessment and manipulative physical therapy management regime, consisting of manual mobilization and exercise focused on retraining the deep cervical flexors and sub-occipital extensors, the patient was left with persistent residual complaints inhibiting competitive level sport participation. Re-assessment and subsequent retraining of a specific provocative functional task was facilitated by using the Cervical Trainer(TM). Using a wireless sensor worn on the head, this device registers three-dimensional movement and displays this on a computer screen, providing direct feedback on movement performance. After a 6-week period of training sessions, the residual complaints subsided and her score on the Headache Impact Test-6 questionnaire improved from 51 to 36 signifying no impact of her headache on daily life activities. PMID- 27252581 TI - Manual physical therapy combined with high-intensity functional rehabilitation for severe lower extremity musculoskeletal injuries: a case series. AB - OBJECTIVES: Severe lower extremity trauma accounts for large healthcare costs and often results in elective amputation and poor long-term outcomes. The purpose of this case series is to describe an orthopedic manual physical therapy (OMPT) approach combined with a return to run (RTR) clinical pathway consisting of high intensity functional rehabilitation with a custom energy-storing orthosis. METHODS: Three consecutive male patients, aged 21-23 years, with severe lower extremity musculoskeletal injuries were treated with a combined intervention that included a mean (SD) of 12 (2.1) OMPT sessions and 24 (8.7) functional rehabilitation sessions over a mean of 6 weeks (1.0). Additional training with a custom energy-storing orthosis consisted of a mean of 15 (1.2) additional sessions over 4 weeks. Patient self-report outcome measures and a variety of physical performance tests captured change in function. RESULTS: Baseline lower extremity functional scale (LEFS) and foot and ankle ability measure activities of daily living subscale (FAAM-ADL) scores indicated severe disability. All patients exceeded the minimal clinically important difference (MCID) in at least one self-report outcome or physical performance test without a brace. Two of three patients exceeded the MCID for at least two physical performance tests after training with and utilizing a custom energy-storing orthosis. DISCUSSION: Clinically meaningful changes in self-reported function or physical performance were observed in all patients. A multi-modal approach, including manual therapy and functional exercise, may address the entire spectrum of impairments in patients with severe lower extremity trauma, resulting in improvements in both braced and un-braced function. PMID- 27252583 TI - Plant Quality Improvement and Nutrigenomics. PMID- 27252582 TI - Multiplanar lumbopelvic control in patients with low back pain: is multiplanar assessment better than single plane assessment in discriminating between patients and healthy controls? AB - OBJECTIVES: Patients with low back pain (LBP) commonly have lumbopelvic control deficits. Lumbopelvic assessment during sagittal motion is incorporated into commonly used clinical examination algorithms for Treatment Based Classification. The purpose of this study was to investigate whether combined assessment of lumbopelvic control during sagittal and frontal plane motion discriminates between people with and without LBP better than single plane assessment alone. METHODS: Nineteen patients with LBP and 18 healthy control participants volunteered for this study. The active straight leg raise (ASLR) and active hip abduction (AHAbd) tests were used to assess lumbopelvic control during sagittal and frontal plane motion, respectively. The tests were scored as positive or negative using published scoring criteria. Contingency tables were created for each test alone and for the combined tests (both positive/both negative) with presence/absence of LBP as the reference standard to calculate accuracy statistics of sensitivity (sn), specificity (sp), likelihood (+LR and -LR), and diagnostic odds ratios (OR). RESULTS: Active straight leg raise and AHAbd tests alone had sn of 0.63, 0.74, respectively, sp of 0.61, 0.50, respectively, and OR of 2.7, 2.8, respectively. The combined tests had sn = 0.89, sp = 0.60, and OR = 12.0. Forty percent of patients with LBP had control deficits in both planes of motion. DISCUSSION: The AHAbd and ALSR tests appear to have greater diagnostic discrimination when used in combination than when used independently. A percentage of patients with LBP had control deficits in both planes, while others demonstrated uniplanar deficits only. These findings highlight the importance of multiplanar assessment in patients with LBP. PMID- 27252585 TI - Molecular Approaches to Understand Nutritional Potential of Coarse Cereals. AB - Coarse grains are important group of crops that constitutes staple food for large population residing primarily in the arid and semi-arid regions of the world. Coarse grains are designated as nutri-cereals as they are rich in essential amino acids, minerals and vitamins. In spite of having several nutritional virtues in coarse grain as mentioned above, there is still scope for improvement in quality parameters such as cooking qualities, modulation of nutritional constituents and reduction or elimination of anti-nutritional factors. Besides its use in traditional cooking, coarse grains have been used mainly in the weaning food preparation and other malted food production. Improvement in quality parameters will certainly increase consumer's preference for coarse grains and increase their demand. The overall genetic gain in quality traits of economic importance in the cultivated varieties will enhance their industrial value and simultaneously increase income of farmers growing these varieties. The urgent step for improvement of quality traits in coarse grains requires a detailed understanding of molecular mechanisms responsible for varied level of different nutritional contents in different genotypes of these crops. In this review we have discussed the progresses made in understanding of coarse grain biology with various omics tool coupled with modern breeding approaches and the current status with regard to our effort towards dissecting traits related to improvement of quality and nutritional constituents of grains. PMID- 27252586 TI - The Contribution of Buckwheat Genetic Resources to Health and Dietary Diversity. AB - Despite several reports on the beneficial effects of buckwheat in prevention of human diseases, little attention has been devoted to the variability of biochemical and physiological traits in different buckwheat genetic resources. This review describes the biochemical evaluation of buckwheat genetic resources and the identification of elite genotypes for plant breeding and exploitation. The various types of bioactive compounds present in different varieties provide basic background information needed for the efficient production of buckwheat foods with added value. In this review, we will provide an integrated view of the biochemistry of bioactive compounds of buckwheat plants of different origin, especially of fagopyrin, proteins and amino acids, as well as of other phenolic compounds including rutin and chlorogenic acid. In addition to the genetic background, the effect of different growth conditions is discussed. The health effects of fagopyrin, phenolic acids, specific proteins and rutin are also presented. PMID- 27252584 TI - Ascribing Functions to Genes: Journey Towards Genetic Improvement of Rice Via Functional Genomics. AB - Rice, one of the most important cereal crops for mankind, feeds more than half the world population. Rice has been heralded as a model cereal owing to its small genome size, amenability to easy transformation, high synteny to other cereal crops and availability of complete genome sequence. Moreover, sequence wealth in rice is getting more refined and precise due to resequencing efforts. This humungous resource of sequence data has confronted research fraternity with a herculean challenge as well as an excellent opportunity to functionally validate expressed as well as regulatory portions of the genome. This will not only help us in understanding the genetic basis of plant architecture and physiology but would also steer us towards developing improved cultivars. No single technique can achieve such a mammoth task. Functional genomics through its diverse tools viz. loss and gain of function mutants, multifarious omics strategies like transcriptomics, proteomics, metabolomics and phenomics provide us with the necessary handle. A paradigm shift in technological advances in functional genomics strategies has been instrumental in generating considerable amount of information w.r.t functionality of rice genome. We now have several databases and online resources for functionally validated genes but despite that we are far from reaching the desired milestone of functionally characterizing each and every rice gene. There is an urgent need for a common platform, for information already available in rice, and collaborative efforts between researchers in a concerted manner as well as healthy public-private partnership, for genetic improvement of rice crop better able to handle the pressures of climate change and exponentially increasing population. PMID- 27252587 TI - Salinity Tolerance Mechanism of Economic Halophytes From Physiological to Molecular Hierarchy for Improving Food Quality. AB - Soil salinity is becoming the key constraints factor to agricultural production. Therefore, the plant especially the crops possessing capacities of salt tolerance will be of great economic significance. The adaptation or tolerance of plant to salinity stress involves a series of physiological, metabolic and molecular mechanisms. Halophytes are the kind of organisms which acquire special salt tolerance mechanisms to respond to the salt tress and ensure normal growth and development under saline conditions in their lengthy evolutionary adaptation, so understanding how halophytes respond to salinity stress will provide us with methods and tactics to foster and develop salt resistant varieties of crops. The strategies in physiological and molecular level adopted by halophytes are various including the changes in photosynthetic and transpiration rate, the sequestration of Na+ to extracellular or vacuole, the regulation of stomata aperture and stomatal density, the accumulation and synthesis of the phytohormones as well as the relevant gene expression underlying these physiological traits, such as the stress signal transduction, the regulation of the transcription factors, the activation and expression of the transporter genes, the activation or inhibition of the synthetases and so on. This review focuses on the research advances of the regulating mechanisms in halophytes from physiological to molecular, which render the halophytes tolerance and adaption to salinity stress. PMID- 27252588 TI - Transport of Calcium Ions into Mitochondria. AB - To uptake calcium ions of mitochondria is of significant functional connotation for cells, because calcium ions in mitochondria are involved in energy production, regulatory signals transfer, and mitochondrial permeability transition pore opening and even programmed cell death of apoptosis, further playing more roles in plant productivity and quality. Cytoplasmic calcium ions access into outer mitochondrial membrane (OMM) from voltage dependent anion selective channel (VDAC) and were absorbed into inner mitochondrial membrane (IMM) by mitochondrial calcium uniporter (MCU), rapid mitochondrial calcium uptake (RaM) or mitochondrial ryanodine receptor (mRyR). Although both mitochondria and the mechanisms of calcium transport have been extensively studied, but there are still long-standing or even new challenges. Here we review the history and recent discoveries of the mitochondria calcium ions channel complex involved calcium assimilation, and discuss the role of calcium ions into mitochondria. PMID- 27252589 TI - Improving Nutritional Quality of Plant Proteins Through Genetic Engineering. AB - Humans and animals are unable to synthesize essential amino acids such as branch chain amino acids methionine (Met), lysine (Lys) and tryptophan (Trp). Therefore, these amino acids need to be supplied through the diets. Several essential amino acids are deficient or completely lacking among crops used for human food and animal feed. For example, soybean is deficient in Met; Lys and Trp are lacking in maize. In this mini review, we will first summarize the roles of essential amino acids in animal nutrition. Next, we will address the question: "What are the amino acids deficient in various plants and their biosynthesis pathways?" And: "What approaches are being used to improve the availability of essential amino acids in plants?" The potential targets for metabolic engineering will also be discussed, including what has already been done and what remains to be tested. PMID- 27252590 TI - Vegetable Oil: Nutritional and Industrial Perspective. AB - Oils of plant origin have been predominantly used for food-based applications. Plant oils not only represent a non-polluting renewable resource but also provide a wide diversity in fatty acids (FAs) composition with diverse applications. Besides being edible, they are now increasingly being used in industrial applications such as paints, lubricants, soaps, biofuels etc. In addition, plants can be engineered to produce fatty acids which are nutritionally beneficial to human health. Thus these oils have potential to 1) substitute ever increasing demand of non -renewable petroleum sources for industrial application and 2) also spare the marine life by providing an alternative source to nutritionally and medically important long chain polyunsaturated fatty acids or 'Fish oil'. The biochemical pathways producing storage oils in plants have been extensively characterized, but the factors regulating fatty acid synthesis and controlling total oil content in oilseed crops are still poorly understood. Thus understanding of plant lipid metabolism is fundamental to its manipulation and increased production. This review on oils discusses fatty acids of nutritional and industrial importance, and approaches for achieving future designer vegetable oil for both edible and non-edible uses. The review will discuss the success and bottlenecks in efficient production of novel FAs in non-native plants using genetic engineering as a tool. PMID- 27252591 TI - Soybean Seed Development: Fatty Acid and Phytohormone Metabolism and Their Interactions. AB - Vegetable oil utilization is determined by its fatty acid composition. In soybean and other grain crops, during the seed development oil accumulation is important trait for value in food or industrial applications. Seed development is relatively short and sensitive to unfavorable abiotic conditions. These stresses can lead to a numerous undesirable qualitative as well as quantitative changes in fatty acid production. Fatty acid manipulation which targets a higher content of a specific single fatty acid for food or industrial application has gained more attention. Despite several successes in modifying the ratio of endogenous fatty acids in most domesticated oilseed crops, numerous obstacles in FA manipulation of seed maturation are yet to be overcome. Remarkably, connections with plant hormones have not been well studied despite their critical roles in the regulation and promotion of a plethora of processes in plant growth and development. While activities of phytohormones during the reproductive phase have been partially clarified in seed physiology, the biological role of plant hormones in oil accumulation during seed development has not been investigated. In this review seed development and numerous effects of abiotic stresses are discussed. After describing fatty acid and phytohormone metabolism and their interactions, we postulate that the endogenous plant hormones play important roles in fatty acid production in soybean seeds. PMID- 27252592 TI - Nutrigenomics and its Impact on Life Style Associated Metabolic Diseases. AB - Post-human genome revelation observes the emergence of 'Nutigenomics' as one of the exciting scientific advancement influencing mankind around the world. Food or more precisely 'nutrition' has the major impact in defining the cause-response interaction between nutrient (diet) and human health. In addition to substantial understanding of nutrition-human-health interaction, bases of 'nutrigenomic' development foster on advent in transcriptomics, genomics, proteomics and metabolomics as well as insight into food as health supplement. Interaction of selected nutrient with associated genes in specific organ or tissue necessary to comprehend that how individual's genetic makeup (DNA transcribed into mRNA and then to proteins) respond to particular nutrient. It provided new opportunities to incorporate natural bioactive compounds into food for specific group of people with similar genotype. As inception of diabetes associated with change in gene expression of, not limited to, protein kinase B, insulin receptor, duodenal homeobox and glucokinase, thus, targeting such proteins by modifying or improving the nutritional availability or uptake may help to devise novel food, supplements, or nutraceuticals. In this article, various aspects of R&D in nutrigenomics are reviewed to ascertain its impact on human health, especially with life-style associated diseases. PMID- 27252594 TI - Liver cancer with concomitant TP53 and CTNNB1 mutations: a case report. AB - BACKGROUND: In the spectrum of molecular alterations found in hepatocellular carcinoma (HCC), somatic mutations in the WNT/beta-catenin pathway and the p53/cell cycle control pathway are among the most frequent ones. It has been suggested that both mutations occur in a mutually exclusive manner and they are used as molecular classifiers in HCC classification proposals. CASE PRESENTATION: Here, we report the case of a treatment-naive mixed hepatocellular/cholangiocellular carcinoma (HCC/CCC) with morphological and genetic intratumor heterogeneity. Within the predominant part of the tumor with hepatocellular differentiation, a p.D32V mutation in exon 3 of the CTNNB1 gene occurred concomitantly with a TP53 intron 7/exon 8 splice site mutation. CONCLUSION: Intratumor heterogeneity challenges the concept of CTNNB1 and TP53 gene mutations being mutually exclusive molecular classifiers in HCC, which has implications for HCC classification approaches. PMID- 27252593 TI - A Comprehensive Review on the Genetic Regulation of Cisplatin-induced Nephrotoxicity. AB - Cisplatin (CDDP) is a well-known antineoplastic drug which has been extensively utilized over the last decades in the treatment of numerous kinds of tumors. However, CDDP induces a wide range of toxicities in a dose-dependent manner, among which nephrotoxicity is of particular importance. Still, the mechanism of CDDP-induced renal damage is not completely understood; moreover, the knowledge about the role of microRNAs (miRNAs) in the nephrotoxic response is still unknown. miRNAs are known to interact with the representative members of a diverse range of regulatory pathways (including postnatal development, proliferation, inflammation and fibrosis) and pathological conditions, including kidney diseases: polycystic kidney diseases (PKDs), diabetic nephropathy (DN), kidney cancer, and drug-induced kidney injury. In this review, we shed light on the following important aspects: (i) information on genes/proteins and their interactions with previously known pathways engaged with CDDP-induced nephrotoxicity, (ii) information on newly discovered biomarkers, especially, miRNAs for detecting CDDP-induced nephrotoxicity and (iii) information to improve our understanding on CDDP. This information will not only help the researchers belonging to nephrotoxicity field, but also supply an indisputable help for oncologists to better understand and manage the side effects induced by CDDP during cancer treatment. Moreover, we provide up-to-date information about different in vivo and in vitro models that have been utilized over the last decades to study CDDP-induced renal injury. Taken together, this review offers a comprehensive network on genes, miRNAs, pathways and animal models which will serve as a useful resource to understand the molecular mechanism of CDDP-induced nephrotoxicity. PMID- 27252596 TI - Retraction Note: Psoriasin (S100A7) is a novel biomarker for lung squamous cell carcinoma in humans. AB - [This retracts the article DOI: 10.1186/s12935-014-0154-0.]. PMID- 27252595 TI - Development and preliminary evaluation of the validity and reliability of a revised illness perception questionnaire for healthcare professionals. AB - BACKGROUND: Diverging perceptions between individual patients with somatic diseases and their healthcare professionals might cause problems in communication and decision-making. To date, no measurement tool is available to compare the illness perceptions between these two groups. The Revised Illness Perception Questionnaire (IPQ-R) is a validated, widely used instrument in many patient populations with somatic conditions. The aim of this study was to adapt the IPQ-R to a healthcare professional's version (IPQ-R HP) and to perform a preliminary evaluation of its validity and reliability. METHODS: After adaptation of the IPQ R HP, 17 doctors from 3 general hospitals and 9 head nurses from a university hospital evaluated the face and content validity of the IPQ-R HP. The results were quantified using the content validity index (CVI) and a modified kappa index (k*). For the reliability measurements a group of nurses from 4 nursing wards participated at 2 time points with an interval of 4 weeks. Internal consistency and test-retest reliability were calculated. RESULTS: Twenty-eight of the 38 items demonstrated excellent content validity and four items showed good content validity. Four items had a sufficient k* and two items had a low CVI. The average CVI of the 7 dimensions ranged from 0.66 to 0.89. The Cronbach's alpha scores for the seven dimensions, intraclass coefficients and effect size estimates were acceptable. CONCLUSIONS: This preliminary evaluation of the IPQ-R HP shows an acceptable to good validity and reliability. Further exploration of the psychometric properties of this questionnaire in a large cohort of healthcare professionals is warranted. PMID- 27252597 TI - Critical Appraisal of Evidence for Improving Gait Speed in People with Multiple Sclerosis: Dalfampridine Versus Gait Training. AB - BACKGROUND: Research has not yet compared the treatment effects of dalfampridine with traditional rehabilitation of gait impairments in multiple sclerosis (MS). The purpose of this review was to critically appraise the evidence for dalfampridine and gait training for increasing gait speed in people with MS. METHODS: A systematic search of the research literature was conducted. Consideration was given to only randomized controlled trials (RCTs), systematic reviews, and meta-analyses. For selection of gait training studies, only studies involving task-specific gait training interventions and measuring treatment effects on gait speed were considered. RESULTS: Treatment effects on gait speed were extracted from four studies examining the efficacy of dalfampridine and six gait training RCTs. Overall mean increase in gait speed with dalfampridine was 0.07 m/s (95% confidence interval [CI], 0.04-0.09 m/s) compared to 0.06 m/s (95% CI, 0.02-0.10 m/s) for gait training. Among dalfampridine responders (38% of participants in RCTs), the mean increase in gait speed was 0.16 m/s (95% CI, 0.13 0.18 m/s). Mean increases for individual gait training interventions ranged from 0.01 to 0.39 m/s; however, CIs were wide due to small sample sizes. CONCLUSIONS: Current evidence is insufficient to conclude whether dalfampridine or gait training is superior for improving gait speed in people with MS. These findings should be viewed cautiously due to differences in study populations and small sample sizes in gait training studies. Both treatment approaches provide only short-lived improvements. Head-to-head comparison trials and studies combining both treatment modalities are needed. PMID- 27252598 TI - Evaluation of a Fatigue Self-Management Program for People with Multiple Sclerosis. AB - BACKGROUND: Fatigue is one of the most common and debilitating symptoms of multiple sclerosis (MS). The program "Minimise Fatigue, Maximise Life: Creating Balance with Multiple Sclerosis" (MFML) was created in New Zealand because of the lack of a fatigue management program for people with MS in that country. This program aims to empower individuals with MS to manage their own symptoms of fatigue. The objective of this study was to evaluate the MFML fatigue self management program. METHODS: Self-report questionnaires were used to measure impact of fatigue (5-item Modified Fatigue Impact Scale), self-efficacy (MS Self efficacy Scale), and quality of life (12-item Short Form Health Status Survey [SF 12]) 1 month before (T1), at commencement of (T2) (to investigate the stability of questionnaire scores before the intervention), and at the end of (T3) the 6 week group-based program. Increased self-efficacy and quality of life scores and a decrease in reported impact of fatigue were the anticipated primary outcomes, with participants acting as their own controls. RESULTS: Twenty-five women (aged 37-63 years) participated. Stability of scores for all the questionnaires was evidenced between T1 and T2. After the intervention (T3), scores showed a significant improvement in self-efficacy and impact of fatigue, with large effect sizes, but no change in either the physical or mental component summary of the SF 12. CONCLUSIONS: Despite the small sample size, this study showed an organized approach to the management of fatigue for people living with MS, and its outcomes demonstrated benefits for participants. PMID- 27252599 TI - Examining the Relationship Between Family Caregivers' Emotional States and Ability to Empathize with Patients with Multiple Sclerosis: A Pilot Study. AB - BACKGROUND: Multiple sclerosis (MS) is the most common nontraumatic cause of disability affecting young adults in Canada. Caregivers of patients with MS are highly psychologically burdened. Empathy and helping behaviors are hallmarks of quality care, but when they are challenged, suboptimal patient care can result. We aimed to evaluate the prevalence of negative emotional states among primary caregivers of people with MS; the association between the caregiver's empathy related behavior and the physical and cognitive impairment of the person with MS; and the association between the caregiver's emotional status and his or her empathy-related behaviors. METHODS: We conducted a descriptive, cross-sectional pilot study with family caregivers of noninstitutionalized individuals living with MS. We used univariate linear regression models for each potential predictor. The Kruskal-Wallis test was conducted to compare differences in caregiver empathic responses depending on Profile of Mood States subscale scores. RESULTS: Thirty percent of caregivers had elevated or very elevated mood scores, and such elevated scores were associated with greater functional impact of MS on the person with MS. Patient severity of cognitive impairment was not associated with caregiver mood scores. Caregiver mood state was not associated with empathy related behaviors. Empathy-related behaviors were less frequent when levels of anger and hostility were higher, but this association did not reach statistical significance. CONCLUSIONS: Given the elevated levels of fatigue, depression, and anger observed among caregivers in this study, clinicians need to be aware of the potential impact of caregiving and to assess the needs of caregivers. PMID- 27252600 TI - Development and Feasibility of an Evidence-Based Patient Education Program for Managing Fatigue in Multiple Sclerosis: The "Fatigue Management in MS" Program (FatiMa). AB - BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. Fatigue is a common and disabling symptom, often causing decreased quality of life, social withdrawal, and unemployment. We developed and studied the feasibility of a cognitive-behavioral group intervention to manage fatigue in MS. We aimed to integrate the concepts of cognitive-behavioral therapy and evidence-based patient information. METHODS: We conducted patient interviews and a focus group to assess patients' interest in and need for fatigue self-management training and developed the program accordingly. The program consists of six 90-minute modules, which were structured with the use of moderation cards, helping to guarantee treatment fidelity. The program was tested on three pilot groups (N = 16) in a rehabilitation center. Fatigue, depression, and coping self-efficacy were assessed at baseline and after the intervention. Acceptance and general satisfaction with the program were also evaluated. RESULTS: Patient interviews elicited different characteristics of fatigue, suggesting that patients had different requirements. The program was very acceptable to patients. Pre-post assessments of the pilot study showed significantly improved scores on the Coping Self-Efficacy Scale (P = .013) but not on the Fatigue Scale for Motor and Cognitive Functions and the 30-item Inventory of Depressive Symptomatology. CONCLUSIONS: These preliminary results suggest that this program is a feasible cognitive-behavioral group training program that may improve coping self-efficacy and has the potential to subsequently reduce fatigue. The next step is evaluation of the program in a randomized controlled trial. PMID- 27252601 TI - Safety and Tolerability of Delayed-Release Dimethyl Fumarate Administered with Interferon Beta or Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis. AB - BACKGROUND: Delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) is indicated for relapsing multiple sclerosis (MS). The objective of this study was to explore the safety and tolerability of DMF when administered with interferon beta (IFNbeta) or glatiramer acetate (GA). METHODS: Patients with relapsing-remitting MS receiving established therapy with the same dose of IFNbeta or GA for at least 12 months continued their prescribed therapy for 2 months (monotherapy period) and then received DMF 240 mg three times daily in addition to their prescribed MS therapy for 6 months (add-on therapy period). Safety and magnetic resonance imaging outcomes were monitored monthly. RESULTS: During the add-on therapy period, in the DMF+IFNbeta (n = 57) and DMF+GA (n = 47) groups, the overall incidence of adverse events was 95% and 100%, respectively; the most common adverse events were flushing, diarrhea, and abdominal pain. In both groups, mean lymphocyte counts decreased but remained within normal limits, and hepatic transaminase levels increased transiently; no case met Hy's law criteria. There was no overall increased risk of infection. In both groups, gadolinium-enhancing lesion activity and new/enlarging T2 lesions decreased compared with the monotherapy period (exploratory endpoints). CONCLUSIONS: The safety profile of DMF taken with IFNbeta or GA was acceptable and consistent with the known safety profile of DMF monotherapy. PMID- 27252602 TI - Symptomatic Management of Multiple Sclerosis-Associated Tremor Among Participants in the NARCOMS Registry. AB - BACKGROUND: Tremor affects 25% to 58% of patients with multiple sclerosis (MS) and is associated with poor prognosis and increased disability. MS-related tremor is difficult to treat, and data regarding patient-reported characterization and response to treatment are limited. We describe the symptomatic treatment of tremor in 508 enrollees in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry who self-reported tremor. METHODS: From 777 surveys sent to NARCOMS participants who indicated mild or greater tremor using the Tremor and Coordination Scale, we compiled data regarding disability, tremor severity, symptomatic medication use, and reported response to medications. RESULTS: Symptomatic medications reported to reduce tremor were used by 238 respondents (46.9%). Symptomatic medication use was associated with increased rates of unemployment and disability, and many other characteristics were similar between groups. Symptomatic drug use was more likely in participants reporting moderate (53.9%) or severe (51.3%) tremor than in those with mild (36.6%) or totally disabling (35.0%) tremor. This disparity held true across multiple tremor severity scores. The most commonly used drug classes were anticonvulsants (50.8%) and benzodiazepines (46.2%), with gabapentin and clonazepam used most often in their respective classes. CONCLUSIONS: Tremor in MS remains poorly treated; less than half of the participants reported benefit from symptomatic medications. Patients with moderate-to-severe tremor are more likely to report tremor benefit than are those with mild or disabling tremor. gamma-Aminobutyric acid-active medications were most commonly reported as beneficial. PMID- 27252604 TI - Editorial. PMID- 27252603 TI - Analysis of Diagnoses Associated with Multiple Sclerosis-Related In-Hospital Mortality Using the Premier Hospital Database. AB - BACKGROUND: We sought to compare mortality rates and related diagnoses in hospitalized patients with multiple sclerosis (MS), those with diabetes mellitus (DM), and the general hospitalized population (GHP). METHODS: Patients who died between 2007 and 2011 were identified in the US hospital-based Premier Healthcare Database. Demographic information was collected, mortality rates calculated, and principal diagnoses categorized. RESULTS: Of 55,152 unique patients with MS identified, 1518 died. Mean age at death was 10 years younger for the MS group (63.4 years) than for the DM (73.3 years) and GHP (73.1 years) groups. Age adjusted mortality rates, based on the 2000 US Standard Million Population, were 1077, 1248, and 1133 per 100,000, respectively. Infection was the most common principal diagnosis at the hospital stay during which the patient died in the MS cohort (43.1% vs. 26.3% and 24.0% in the DM and GHP groups, respectively). Other common principal diagnoses in the MS group included pulmonary (17.5%) and cardiovascular (12.1%) disease. Septicemia/sepsis/septic shock was a secondary diagnosis for 50.7% of patients with MS versus 36.0% and 31.0% of patients in the DM and GHP cohorts, respectively. CONCLUSIONS: Patients with MS had a shorter life span than patients with DM or the GHP and were more likely to have a principal diagnosis of infection at their final hospital stay. However, the database was limited to codes recorded in the hospital; diagnoses received outside the hospital were not captured. PMID- 27252605 TI - [Not Available]. AB - This is an epidemiologic study of the need for Health Services for burns in the northern part of Franche Comte (north-east of France) along year 2014 (114 patients). Mean age was 26 years (8 month-81 years), one third of burns occurred in children below 15. Most burns take part in summer, around mealtime, in "school free" days, at home and are scalds. Their surface is low (4,81%) and they are usually partial thickness ones. Patients are consulted in Emergency Department in 88,59% of the cases, and hospitalised thereafter in a Burns Unit (in Lyon more than Nancy or Metz) in 12,28%. PMID- 27252606 TI - Development of an effective communication strategy for the prevention of burns in children: the PRIUS project. AB - This study has developed a learning kit for the prevention of domestic burns in childhood. The main objective was to trial an educational package for children (nursery and primary classes), for the prevention of burns, to be implemented through education in schools. The educational kit comprises posters, information leaflets, comic books, and pre and post education evaluation materials for school children, parents and teachers. Recipients of the preliminary study were the students of nine schools in the eight Italian cities where Burn Centers are located. In order to reach the target groups of children, it was necessary to identify the most effective communication strategy to convey the burn prevention message. For nursery school children, it was not possible to use tools with written texts alone, as they were not yet literate. Moreover, even for older children, it was necessary to find an attractive tool to catch their attention and interest, promoting the understanding and memorization of lessons learned. The most suitable means was found to be comic strips, allowing the messages to be conveyed through images as well as words. A total of 370 children (195 from nurseries and 175 from primary schools) participated in the trial of the educational kit. Overall, for every environment represented in the evaluation table, the ability to recognize the dangers among both the pre-school and primary school children increased significantly after the training activity. In conclusion, the educational kit has been positively assessed. PMID- 27252607 TI - [Not Available]. AB - Mortality in burn patients is most often caused by infections, which are frequently bacterial. These patients are subject to loss of the cutaneous barrier, invasive devices and immunosuppression which are all contributing factors to the onset of infections. Unfortunately, it is not easy to distinguish general signs of infection from other symptoms associated with burn injuries, making diagnosis difficult. Since infection is a great threat in burns patients, its prevention is a fundamental part of the treatment process. Moreover, due to the anomalous pharmacokinetic characteristics of burns patients, it is also mandatory to adapt any antimicrobial regimen to the outcomes of regular patient blood tests and sampling. At a time when bacterial resistance is becoming an increasing concern, research on alternative treatment (e.g. inhibitors of virulence factors, antimicrobial peptides, polyphenols, immunotherap, and so on) is crucial. One of the more promising possibilities in this area seems to be phagotherapy. PMID- 27252608 TI - Progress in burns research: a review of advances in burn pathophysiology. AB - Severe burns trigger a wide range of responses in the victim. Initial vascular changes are followed by hypermetabolic, inflammatory and immunologic changes. The prolonged hypermetabolic response is associated with an elevated resting rate of energy consumption, tissue wasting and altered substrate kinetics. There is increased blood glucose though insulin levels are above normal. The cortisol level is raised and, together with catecholamine, drives the metabolic response. The immune system is typically weakened. There is elevation in blood levels of a wide range of cytokines from activated cells. These agents drive a prolonged inflammatory response which can lead to tissue damage and multiple organ failure. Dynamic fluid resuscitation regimens have cut down mortality from shock in the early post-burn period. However, unbalanced activity of pro- and anti inflammatory cytokines can leave patients in an immuno-suppressed state that affects outcomes. So far, many treatments, such as propranolol, a cardio protector, and anabolic agents, such as oxandrolone and growth hormone, have been tried with mixed results. This review focuses on research that elucidated burn pathophysiology. Some clinical areas in which treatment centred on correcting altered physiology were also included. We have highlighted both the challenges and significant findings. Finally, this paper draws attention to the gaps between progress in basic research and clinical application and suggests areas where further research and funding could be focused. PMID- 27252609 TI - Procalcitonin: a diagnostic and prognostic biomarker of sepsis in burned patients. AB - The goal of this study was to analyse plasma procalcitonin (PCT) concentrations during infectious events of burns in ICU. We conducted a prospective, observational study in a 20-bed Burn Intensive Care Unit in Tunisia. A total of 121 patients admitted to the Burn ICU were included in our study. Serum PCT was measured over the entire course of stay in patients with predictive signs of sepsis according to the Americain Burn Association Criteria for the presence of infection. Patients were assigned to two groups depending on the clinical course and outcome: Group A = non septic patients; Group B = septic patients. A PCT cutoff value of 0,69 ng/ml for sepsis prediction was associated with the optimal combination of sensitivity (89%), specificity (85%), positive predictive value (82%) and negative predictive value (88%). Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injuries as well as in monitoring the response to antimicrobial therapy. PMID- 27252610 TI - Treatment of nasal burns: analysis of 150 cases. AB - Nasal burns present a challenge for the plastic surgeon in terms of immediate management, choice of primary treatment and secondary reconstruction with the goals of good aesthetic and functional outcome. We present a retrospective analysis of the management of 150 patients with nasal burns treated in our center between July 2005 and July 2011. We rationalized our conservative and all surgical treatments of this subset of burns patients and organized them in a simple and structured way. The reconstructive options for most complex full thickness nasal injury is determined by the integrity of adjacent facial tissues which would always be preferred when available. Microsurgical free tissue transfer is dependent upon the fitness of the patient and the availability of unburned skin at the donor site. Secondary nasal reconstruction is based on an assessment of the residual functional and cosmetic problems. Airways narrowing from scar contracture or loss of support are managed using standard plastic surgical and rhinoplasty principles. Cosmetic refinements range from flap debulking to the importation of new tissue on to the nose. Our experience with this challenging group of patients has led us to develop a simple treatment algorithm for the management of nasal burns. PMID- 27252611 TI - Epidemiology of pneumonia in a burn care unit: the influence of inhalation trauma on pneumonia and of pneumonia on burn mortality. AB - The aim of this study is to determine the epidemiological characteristics of burn patients developing pneumonia, as well as the predisposing factors and the mortality of these patients. Infectious complications present serious problems in severely burned patients. Pneumonia, in particular, is a major cause of morbidity and mortality in burn patients. Patients with inhalation injuries are exposed to a greater risk due to the possible development of infectious complications in the lower respiratory tract. During their stay in our Burn Care Unit, 22.9% of our burn patients developed pneumonia and 10.9 % of these patients died. Risk factors for the development of pneumonia in burn patients were found to be inhalation trauma, high ABSI score, the Baux and modified Baux index, and high ASA score (p<0.01). Age and gender showed no significant correlation to the incidence of pneumonia. In this study we were able to determine the incidence of pneumonia in burn patients, their mortality and the strong correlation of the presence of inhalation injury with the development of pneumonia. PMID- 27252612 TI - Topical use of Rectogesic(r) and Emla(r) to improve cutaneous blood perfusion following thermal injury. A comparative experimental study. AB - Early post-burn ischemic necrosis of the skin is of particular interest in modern burn research. The purpose of this study was to test the hypothesis that blood perfusion could be improved by the topical application of vasoactive substances. A sample of 55 wistar rats was used to investigate the effect of 0,4% nitroglycerin ointment (Rectogesic((r))) comparatively to no application and placebo. The beneficiary action of 5% prilocaine/lidocaine cream (EMLA((r))) in burn blood perfusion was also tested comparatively to Rectogesic((r)). Both preparations were tested respectively to non burned controls. Laser Doppler assessment of blood flow at 15, 30, 45, 60, 120 and 180 minutes after preparation application, demonstrated that the use of Rectogesic((r)) improved perfusion at all measurements compared to placebo and to no preparation application (p&0,05). There was no statistical significant difference in the effect of the two preparations. PMID- 27252613 TI - [Not Available]. AB - The association of burns and epilepsy is frequent in Morocco. These burns, often recurring, mainly occur in young women living in rural areas. The accidents usually occur in the kitchen and involve falling onto stoves situated on the floor during an epileptic crisis. Such burns may occur during a first attack before epilepsy has been diagnosed although, more often than not, the patient's illness is already known but insufficiently treated and managed. Consequences of these burns, which are always deep, are often tragic considering the sequelae, in patients whose social reintegration is already marred by epilepsy. Treatment should focus on both burns and epilepsy. Preventive measures to keep the epilepsy in check and avoid these sufferers being left alone in proximity to heat sources should be put in place. PMID- 27252614 TI - Suicidal behavior by burns among women in two bordering provinces in Iran. AB - The objective of the study was to describe epidemiologic features of suicidal behavior by burns among women in two bordering provinces in Iran. A prospective hospital-based study of all suicidal behaviors by burns among women was carried out in the Iranian provinces of Khorasan (which borders Afghanistan) and Ilam (which borders Iraq) in 2006. These two provinces suffered from war and economic instability with high rates of poverty and unemployment. Data were obtained from patients, family members, and/or significant others through interviews during the course of hospitalization. Of 181 hospitalized patients, 130 (71.8%) were female, representing a hospital separation rate of 5.4 per 100,000 person-year (P-Y). The rate of suicidal behavior involving burns among the rural population was higher than that in the urban population (6.3 vs. 4.7 per 100,000 P-Y, P = 0.09). The median age of the patients was 23 years old, with a mean (+/-SD) of 27.9 (+/ 14.3) years old. Approximately 68.5% of women were married. Quarrels with "a family member, spouse, a relative, or a friend" (marital plus other conflicts) was identified as the most common precipitating factor (88.5%) in attempting suicide. More than one third of women were abused (physically and/or verbally) by family members (i.e. spouse, father-in-law). Case fatality rate in this study was 52.3% (68/130). Suicide by burns is still a socio-epidemiological problem in Iran, particularly among young, married women in rural areas. Social and economic conditions, as well as violence against women, play a major role in the high rate of suicide by burns. The findings of this study highlight the need for the implementation of a well-organized approach to reduce the rate of suicide by burns among the most vulnerable populations in Iran. PMID- 27252615 TI - [Not Available]. PMID- 27252616 TI - MBC News. PMID- 27252618 TI - Amygdala and Emotion: The Bright Side of It. PMID- 27252619 TI - Measuring Neural Entrainment to Beat and Meter in Infants: Effects of Music Background. AB - Caregivers often engage in musical interactions with their infants. For example, parents across cultures sing lullabies and playsongs to their infants from birth. Behavioral studies indicate that infants not only extract beat information, but also group these beats into metrical hierarchies by as early as 6 months of age. However, it is not known how this is accomplished in the infant brain. An EEG frequency-tagging approach has been used successfully with adults to measure neural entrainment to auditory rhythms. The current study is the first to use this technique with infants in order to investigate how infants' brains encode rhythms. Furthermore, we examine how infant and parent music background is associated with individual differences in rhythm encoding. In Experiment 1, EEG was recorded while 7-month-old infants listened to an ambiguous rhythmic pattern that could be perceived to be in two different meters. In Experiment 2, EEG was recorded while 15-month-old infants listened to a rhythmic pattern with an unambiguous meter. In both age groups, information about music background (parent music training, infant music classes, hours of music listening) was collected. Both age groups showed clear EEG responses frequency-locked to the rhythms, at frequencies corresponding to both beat and meter. For the younger infants (Experiment 1), the amplitudes at duple meter frequencies were selectively enhanced for infants enrolled in music classes compared to those who had not engaged in such classes. For the older infants (Experiment 2), amplitudes at beat and meter frequencies were larger for infants with musically-trained compared to musically-untrained parents. These results suggest that the frequency-tagging method is sensitive to individual differences in beat and meter processing in infancy and could be used to track developmental changes. PMID- 27252620 TI - Commentary: Lack of functional specialization of neurons in the mouse primary visual cortex that have expressed calretinin. PMID- 27252617 TI - Multi-Target Directed Donepezil-Like Ligands for Alzheimer's Disease. AB - HIGHLIGHTS ASS234 is a MTDL compound containing a moiety from Donepezil and the propargyl group from the PF 9601N, a potent and selective MAO B inhibitor. This compound is the most advanced anti-Alzheimer agent for preclinical studies identified in our laboratory.Derived from ASS234 both multipotent donepezil indolyl (MTDL-1) and donepezil-pyridyl hybrids (MTDL-2) were designed and evaluated as inhibitors of AChE/BuChE and both MAO isoforms. MTDL-2 showed more high affinity toward the four enzymes than MTDL-1.MTDL-3 and MTDL-4, were designed containing the N-benzylpiperidinium moiety from Donepezil, a metal- chelating 8-hydroxyquinoline group and linked to a N-propargyl core and they were pharmacologically evaluated.The presence of the cyano group in MTDL-3, enhanced binding to AChE, BuChE and MAO A. It showed antioxidant behavior and it was able to strongly complex Cu(II), Zn(II) and Fe(III).MTDL-4 showed higher affinity toward AChE, BuChE.MTDL-3 exhibited good brain penetration capacity (ADMET) and less toxicity than Donepezil. Memory deficits in scopolamine-lesioned animals were restored by MTDL-3.MTDL-3 particularly emerged as a ligand showing remarkable potential benefits for its use in AD therapy. Alzheimer's disease (AD), the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills, and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, beta amyloid deposits, tau-protein phosphorylation, oxidative stress, and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept(r)) but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands (MTDL) based on the "one molecule, multiple targets" paradigm. Thus, in this context, different series of novel multifunctional molecules with antioxidant, anti-amyloid, anti-inflammatory, and metal-chelating properties able to interact with multiple enzymes of therapeutic interest in AD pathology including acetylcholinesterase, butyrylcholinesterase, and monoamine oxidases A and B have been designed and assessed biologically. This review describes the multiple targets, the design rationale and an in-house MTDL library, bearing the N benzylpiperidine motif present in donepezil, linked to different heterocyclic ring systems (indole, pyridine, or 8-hydroxyquinoline) with special emphasis on compound ASS234, an N-propargylindole derivative. The description of the in vitro biological properties of the compounds and discussion of the corresponding structure-activity-relationships allows us to highlight new issues for the identification of more efficient MTDL for use in AD therapy. PMID- 27252621 TI - Coding Deficits in Noise-Induced Hidden Hearing Loss May Stem from Incomplete Repair of Ribbon Synapses in the Cochlea. AB - Recent evidence has shown that noise-induced damage to the synapse between inner hair cells (IHCs) and type I afferent auditory nerve fibers (ANFs) may occur in the absence of permanent threshold shift (PTS), and that synapses connecting IHCs with low spontaneous rate (SR) ANFs are disproportionately affected. Due to the functional importance of low-SR ANF units for temporal processing and signal coding in noisy backgrounds, deficits in cochlear coding associated with noise induced damage may result in significant difficulties with temporal processing and hearing in noise (i.e., "hidden hearing loss"). However, significant noise induced coding deficits have not been reported at the single unit level following the loss of low-SR units. We have found evidence to suggest that some aspects of neural coding are not significantly changed with the initial loss of low-SR ANFs, and that further coding deficits arise in association with the subsequent reestablishment of the synapses. This suggests that synaptopathy in hidden hearing loss may be the result of insufficient repair of disrupted synapses, and not simply due to the loss of low-SR units. These coding deficits include decreases in driven spike rate for intensity coding as well as several aspects of temporal coding: spike latency, peak-to-sustained spike ratio and the recovery of spike rate as a function of click-interval. PMID- 27252622 TI - Evaluation of Gene Therapy as an Intervention Strategy to Treat Brain Injury from Stroke. AB - Stroke is a leading cause of death and disability, with a lack of treatments available to prevent cell death, regenerate damaged cells and pathways, or promote neurogenesis. The extended period of hours to weeks over which tissue damage continues to occur makes this disorder a candidate for gene therapy. This review highlights the development of gene therapy in the area of stroke, with the evolution of viral administration, in experimental stroke models, from pre-injury to clinically relevant timeframes of hours to days post-stroke. The putative therapeutic proteins being examined include anti-apoptotic, pro-survival, anti inflammatory, and guidance proteins, targeting multiple pathways within the complex pathology, with promising results. The balance of findings from animal models suggests that gene therapy provides a viable translational platform for treatment of ischemic brain injury arising from stroke. PMID- 27252623 TI - Reduced Glutamatergic Currents and Dendritic Branching of Layer 5 Pyramidal Cells Contribute to Medial Prefrontal Cortex Deactivation in a Rat Model of Neuropathic Pain. AB - Multiple studies have demonstrated that neuropathic pain is associated with major reorganization in multiple brain areas. In line with the strong emotional salience of chronic pain, involvement of the limbic system appears particularly important. Within the past few years, it has become clear that the functional deactivation of the prefrontal cortex (PFC) is critical for both the cognitive/emotional and the sensory components of pain. However, at the cellular level, details of this deactivation remain in large part unclear. Here we show that 1 week after a peripheral neuropathic injury (Spared Nerve Injury model) pyramidal cells in layer 5 (L5) of the rat medial PFC show responses to excitatory glutamatergic inputs that are reduced by about 50%, as well as reduced frequency of spontaneous excitatory synaptic currents. Additionally, these cells have reduced membrane capacitance and increased input resistance. All these findings are consistent with decreased dendritic length, thus we performed a detailed morphological analysis on a subset of the recorded neurons. We found that the apical dendrites proximal to the soma (excluding the tuft) are shorter and less complex in SNI animals, in agreement with the reduced capacitance and glutamatergic input. Finally, we used in vivo microdialysis to compare the basal concentrations of glutamate and GABA in the PFC of sham and SNI rats and found that ambient glutamate is decreased in SNI rats. Taken together, these data show that impaired glutamatergic transmission contributes to the functional deactivation of the mPFC in neuropathic pain. Additionally, the reduced branching of apical dendrites of L5 pyramidal neurons may underlay the gray matter reduction in chronic pain. PMID- 27252624 TI - Alterations of Cell Proliferation and Apoptosis in the Hypoplastic Reeler Cerebellum. AB - A mutation of the reln gene gives rise to the Reeler mouse (reln (-/-)) displaying an ataxic phenotype and cerebellar hypoplasia. We have characterized the neurochemistry of postnatal (P0-P60) reln (-/-) mouse cerebella with specific attention to the intervention of cell proliferation and apoptosis in the P0-P25 interval. Homozygous reln (-/-) mice and age-matched controls were analyzed by immunofluorescence using primary antibodies against NeuN, calbindin, GFAP, vimentin, SMI32, and GAD67. Proliferation and apoptosis were detected after a single intraperitoneal BrdU injection and by the TUNEL assay with anti digoxigenin rhodamine-conjugated antibodies. Quantitative analysis with descriptive and predictive statistics was used to calculate cell densities (number/mm(2)) after fluorescent nuclear stain (TCD, total cell density), labeling with BrdU (PrCD, proliferating cell density), or TUNEL (ApoCD, apoptotic cell density). By this approach we first have shown that the temporal pattern of expression of neuronal/glial markers in postnatal cerebellum is not affected by the Reeler mutation. Then, we have demonstrated that the hypoplasia in the Reeler mouse cerebellum is consequent to reduction of cortical size and cellularity (TCD), and that TCD is, in turn, linked to quantitative differences in the extent of cell proliferation and apoptosis, as well as derangements in their temporal trends during postnatal maturation. Finally, we have calculated that PrCD is the most important predictive factor to determine TCD in the cerebellar cortex of the mutants. These results support the notion that, beside the well-known consequences onto the migration of the cerebellar neurons, the lack of Reelin results in a measurable deficit in neural proliferation. PMID- 27252625 TI - Combining TMS and tACS for Closed-Loop Phase-Dependent Modulation of Corticospinal Excitability: A Feasibility Study. AB - BACKGROUND: The corticospinal excitability indexed by motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) of the sensorimotor cortex is characterized by large variability. The instantaneous phase of cortical oscillations at the time of the stimulation has been suggested as a possible source of this variability. To explore this hypothesis, a specific phase needs to be targeted by TMS pulses with high temporal precision. OBJECTIVE: The aim of this feasibility study was to introduce a methodology capable of exploring the effects of phase-dependent stimulation by the concurrent application of alternating current stimulation (tACS) and TMS. METHOD: We applied online calibration and closed-loop TMS to target four specific phases (0 degrees , 90 degrees , 180 degrees and 270 degrees ) of simultaneous 20 Hz tACS over the primary motor cortex (M1) of seven healthy subjects. RESULT: The integrated stimulation system was capable of hitting the target phase with high precision (SD +/- 2.05 ms, i.e., +/- 14.45 degrees ) inducing phase-dependent MEP modulation with a phase lag (CI95% = -40.37 degrees to -99.61 degrees ) which was stable across subjects (p = 0.001). CONCLUSION: The combination of different neuromodulation techniques facilitates highly specific brain state-dependent stimulation, and may constitute a valuable tool for exploring the physiological and therapeutic effect of phase-dependent stimulation, e.g., in the context of neurorehabilitation. PMID- 27252627 TI - A New Defective Helper RNA to Produce Recombinant Sindbis Virus that Infects Neurons but does not Propagate. AB - Recombinant Sindbis viruses are important tools in neuroscience because they combine rapid and high transgene expression with a capacity to carry large transgenes. Currently, two packaging systems based on the defective helper (DH) RNAs DH(26S)5'SIN and DH-BB(tRNA;TE12) are available for generating recombinant Sindbis virus that is neurotropic (able to infect neurons and potentially other cells). Both systems produce a fraction of viral particles that can propagate beyond the primary infected neuron. When injected into mouse brain, viruses produced using these DH RNAs produce transgene expression at the injection site, but also elsewhere in the brain. Such ectopic labeling caused recombinant Sindbis viruses to be classified as anterograde viruses with limited retrograde spread, and can complicate the interpretation of neuroanatomical and other experiments. Here we describe a new DH RNA, DH-BB(5'SIN;TE12ORF), that can be used to produce virus that is both neurotropic and propagation-incompetent. We show in mice that DH-BB(5'SIN;TE12ORF)-packaged virus eliminates infection of cells outside the injection site. We also provide evidence that ectopically labeled cells observed in previous experiments with recombinant Sindbis virus resulted from secondary infection by propagation-competent virus, rather than from inefficient retrograde spread. Virus produced with our new packaging system retains all the advantages of previous recombinant Sindbis viruses, but minimizes the risks of confounding results with unwanted ectopic labeling. It should therefore be considered in future studies in which a neurotropic, recombinant Sindbis virus is needed. PMID- 27252626 TI - Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions. AB - Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long lasting neuronal deficits. PMID- 27252628 TI - Cortical Terminations of the Inferior Fronto-Occipital and Uncinate Fasciculi: Anatomical Stem-Based Virtual Dissection. AB - We combined the neuroanatomists' approach of defining a fascicle as all fibers passing through its compact stem with diffusion-weighted tractography to investigate the cortical terminations of two association tracts, the inferior fronto-occipital fasciculus (IFOF) and the uncinate fasciculus (UF), which have recently been implicated in the ventral language circuitry. The aim was to provide a detailed and quantitative description of their terminations in 60 healthy subjects and to do so to apply an anatomical stem-based virtual dissection, mimicking classical post-mortem dissection, to extract with minimal a priori the IFOF and UF from tractography datasets. In both tracts, we consistently observed more extensive termination territories than their conventional definitions, within the middle and superior frontal, superior parietal and angular gyri for the IFOF and the middle frontal gyrus and superior, middle and inferior temporal gyri beyond the temporal pole for the UF. We revealed new insights regarding the internal organization of these tracts by investigating for the first time the frequency, distribution and hemispheric asymmetry of their terminations. Interestingly, we observed a dissociation between the lateral right-lateralized and medial left-lateralized fronto occipital branches of the IFOF. In the UF, we observed a rightward lateralization of the orbito-frontal and temporal branches. We revealed a more detailed map of the terminations of these fiber pathways that will enable greater specificity for correlating with diseased populations and other behavioral measures. The limitations of the diffusion tensor model in this study are also discussed. We conclude that anatomical stem-based virtual dissection with diffusion tractography is a fruitful method for studying the structural anatomy of the human white matter pathways. PMID- 27252629 TI - Compensatory Recovery after Multisensory Stimulation in Hemianopic Patients: Behavioral and Neurophysiological Components. AB - Lateralized post-chiasmatic lesions of the primary visual pathway result in loss of visual perception in the field retinotopically corresponding to the damaged cortical area. However, patients with visual field defects have shown enhanced detection and localization of multisensory audio-visual pairs presented in the blind field. This preserved multisensory integrative ability (i.e., crossmodal blindsight) seems to be subserved by the spared retino-colliculo-dorsal pathway. According to this view, audio-visual integrative mechanisms could be used to increase the functionality of the spared circuit and, as a consequence, might represent an important tool for the rehabilitation of visual field defects. The present study tested this hypothesis, investigating whether exposure to systematic multisensory audio-visual stimulation could induce long-lasting improvements in the visual performance of patients with visual field defects. A group of 10 patients with chronic visual field defects were exposed to audio visual training for 4 h daily, over a period of 2 weeks. Behavioral, oculomotor and electroencephalography (EEG) measures were recorded during several visual tasks before and after audio-visual training. After audio-visual training, improvements in visual search abilities, visual detection, self-perceived disability in daily life activities and oculomotor parameters were found, suggesting the implementation of more effective visual exploration strategies. At the electrophysiological level, after training, patients showed a significant reduction of the P3 amplitude in response to stimuli presented in the intact field, reflecting a reduction in attentional resources allocated to the intact field, which might co-occur with a shift of spatial attention towards the blind field. More interestingly, both the behavioral improvements and the electrophysiological changes observed after training were found to be stable at a follow-up session (on average, 8 months after training), suggesting long-term effects of multisensory audio-visual training. These long-lasting effects seem to be subserved by the activation of the spared retino-colliculo-dorsal pathway, which promotes orienting responses towards the blind field, able to both compensate for the visual field loss and concurrently attenuate visual attention towards the intact field. These results add to previous findings the knowledge that audio-visual multisensory stimulation promote long-term plastic changes in hemianopics, resulting in stable and long-lasting ameliorations in behavioral and electrophysiological measures. PMID- 27252630 TI - Commentary: Perceptual learning in autism: over-specificity and possible remedies. PMID- 27252631 TI - Single Neurons in the Insular Cortex of a Macaque Monkey Respond to Skin Brushing: Preliminary Data of the Possible Representation of Pleasant Touch. AB - Pleasant touch may serve as a foundation for affiliative behavior, providing a mechanism for the formation and maintenance of social bonds among conspecifics. In humans, this touch is usually referred to as the caress. Dynamic caressing performed on the hairy skin with a velocity of 1-10 cm/s is perceived as being pleasant and determines positive cardio-physiological effects. Furthermore, imaging human studies show that affiliative touch activates the posterior insular cortex (pIC). Recently, it was demonstrated that pleasant touch in monkeys (i.e., sweeping in a grooming-like manner) is performed with velocities similar to those characteristics of human caress (9.31 cm/s), and causes similarly positive autonomic effects, if performed with velocity of 5 cm/s and 10 cm/s, but not lower or higher. Due to similarities between the human caress and non-human primate sweeping, we investigated for the first time whether single neurons of the perisylvian regions (secondary somatosensory cortex [SII] and pIC) of a rhesus monkey can process sweeping touch differently depending on the stimulus speed. We applied stimulation with two speeds: one that optimally induces positive cardio-physiological effects in the monkey who receives it, and includes the real speed of sweep (5-15 cm/s, sweep fast), and a non-optimal speed (1-5 cm/s, sweep slow). The results show that single neurons of insular cortex differently encode the stimulus speed. In particular, even the majority of recorded somatosensory neurons (82.96%) did not discriminate the two speeds, a small set of neurons (16.59%) were modulated just during the sweep fast. These findings represent the first evidence that single neurons of the non-human primates insular cortex can code affiliative touch, highlighting the similarity between human and non-human primates' social touch systems. This study constitutes an important starting point to carry out deeper investigation on neuronal processing of pleasant sweeping in the central nervous system. PMID- 27252632 TI - Neural Substrates of Semantic Prospection - Evidence from the Dementias. AB - The ability to envisage personally relevant events at a future time point represents an incredibly sophisticated cognitive endeavor and one that appears to be intimately linked to episodic memory integrity. Far less is known regarding the neurocognitive mechanisms underpinning the capacity to envisage non-personal future occurrences, known as semantic future thinking. Moreover the degree of overlap between the neural substrates supporting episodic and semantic forms of prospection remains unclear. To this end, we sought to investigate the capacity for episodic and semantic future thinking in Alzheimer's disease (n = 15) and disease-matched behavioral-variant frontotemporal dementia (n = 15), neurodegenerative disorders characterized by significant medial temporal lobe (MTL) and frontal pathology. Participants completed an assessment of past and future thinking across personal (episodic) and non-personal (semantic) domains, as part of a larger neuropsychological battery investigating episodic and semantic processing, and their performance was contrasted with 20 age- and education-matched healthy older Controls. Participants underwent whole-brain T1 weighted structural imaging and voxel-based morphometry analysis was conducted to determine the relationship between gray matter integrity and episodic and semantic future thinking. Relative to Controls, both patient groups displayed marked future thinking impairments, extending across episodic and semantic domains. Analyses of covariance revealed that while episodic future thinking deficits could be explained solely in terms of episodic memory proficiency, semantic prospection deficits reflected the interplay between episodic and semantic processing. Distinct neural correlates emerged for each form of future simulation with differential involvement of prefrontal, lateral temporal, and medial temporal regions. Notably, the hippocampus was implicated irrespective of future thinking domain, with the suggestion of lateralization effects depending on the type of information being simulated. Whereas episodic future thinking related to right hippocampal integrity, semantic future thinking was found to relate to left hippocampal integrity. Our findings support previous observations of significant MTL involvement for semantic forms of prospection and point to distinct neurocognitive mechanisms which must be functional to support future oriented forms of thought across personal and non-personal contexts. PMID- 27252633 TI - Reduced Functional Connectivity within the Mesocorticolimbic System in Substance Use Disorders: An fMRI Study of Puerto Rican Young Adults. AB - Studies of the mesocorticolimbic reward system (MCLS) and its relationship with impulsivity and substance use disorders (SUD) have largely focused on individuals from non-minority backgrounds. This represents a significant gap in the literature particularly for minority populations who are disproportionately affected by the consequences of SUD. Using resting-state functional MRI (fMRI), we examined the coherence of neural activity, or functional connectivity, within the brain's MCLS in 28 young adult Puerto Ricans (ages 25-27) who were part of a population-based cohort study. Half of the sample lived in San Juan, Puerto Rico; the other half lived in the South Bronx, New York. At each of the two sites, half of the sample had a history of a SUD. Relative to those without SUD, individuals with SUD had decreased connectivity between the nucleus accumbens (NAcc) and several regions within the MCLS. This finding was true irrespective of study site (i.e., San Juan or South Bronx). Reduced connectivity within the MCLS was also associated with higher self-reported levels of impulsivity. Path analysis suggested a potential mechanism linking impulsivity, the MCLS, and SUD: impulsivity, potentially by chronically promoting reward seeking behaviors, may contribute to decreased MCLS connectivity, which in turn, may confer vulnerability for SUD. Expanding upon prior studies suggesting that alterations within the MCLS underlie SUD, our findings suggest that such alterations are also related to impulsivity and are present in a high-risk young minority population. PMID- 27252634 TI - A Complex Story: Universal Preference vs. Individual Differences Shaping Aesthetic Response to Fractals Patterns. AB - Fractal patterns offer one way to represent the rough complexity of the natural world. Whilst they dominate many of our visual experiences in nature, little large-scale perceptual research has been done to explore how we respond aesthetically to these patterns. Previous research (Taylor et al., 2011) suggests that the fractal patterns with mid-range fractal dimensions (FDs) have universal aesthetic appeal. Perceptual and aesthetic responses to visual complexity have been more varied with findings suggesting both linear (Forsythe et al., 2011) and curvilinear (Berlyne, 1970) relationships. Individual differences have been found to account for many of the differences we see in aesthetic responses but some, such as culture, have received little attention within the fractal and complexity research fields. This two-study article aims to test preference responses to FD and visual complexity, using a large cohort (N = 443) of participants from around the world to allow universality claims to be tested. It explores the extent to which age, culture and gender can predict our preferences for fractally complex patterns. Following exploratory analysis that found strong correlations between FD and visual complexity, a series of linear mixed-effect models were implemented to explore if each of the individual variables could predict preference. The first tested a linear complexity model (likelihood of selecting the more complex image from the pair of images) and the second a mid-range FD model (likelihood of selecting an image within mid-range). Results show that individual differences can reliably predict preferences for complexity across culture, gender and age. However, in fitting with current findings the mid-range models show greater consistency in preference not mediated by gender, age or culture. This article supports the established theory that the mid-range fractal patterns appear to be a universal construct underlying preference but also highlights the fragility of universal claims by demonstrating individual differences in preference for the interrelated concept of visual complexity. This highlights a current stalemate in the field of empirical aesthetics. PMID- 27252635 TI - Saccade Adaptation and Visual Uncertainty. AB - Visual uncertainty may affect saccade adaptation in two complementary ways. First, an ideal adaptor should take into account the reliability of visual information for determining the amount of correction, predicting that increasing visual uncertainty should decrease adaptation rates. We tested this by comparing observers' direction discrimination and adaptation rates in an intra-saccadic step paradigm. Second, clearly visible target steps may generate a slower adaptation rate since the error can be attributed to an external cause, instead of an internal change in the visuo-motor mapping that needs to be compensated. We tested this prediction by measuring saccade adaptation to different step sizes. Most remarkably, we found little correlation between estimates of visual uncertainty and adaptation rates and no slower adaptation rates with more visible step sizes. Additionally, we show that for low contrast targets backward steps are perceived as stationary after the saccade, but that adaptation rates are independent of contrast. We suggest that the saccadic system uses different position signals for adapting dysmetric saccades and for generating a trans saccadic stable visual percept, explaining that saccade adaptation is found to be independent of visual uncertainty. PMID- 27252636 TI - Common Genetic Variant in VIT Is Associated with Human Brain Asymmetry. AB - Brain asymmetry varies across individuals. However, genetic factors contributing to this normal variation are largely unknown. Here we studied variation of cortical surface area asymmetry in a large sample of subjects. We performed principal component analysis (PCA) to capture correlated asymmetry variation across cortical regions. We found that caudal and rostral anterior cingulate together account for a substantial part of asymmetry variation among individuals. To find SNPs associated with this subset of brain asymmetry variation we performed a genome-wide association study followed by replication in an independent cohort. We identified one SNP (rs11691187) that had genome-wide significant association (P Combined = 2.40e-08). The rs11691187 is in the first intron of VIT. In a follow-up analysis, we found that VIT gene expression is associated with brain asymmetry in six donors of the Allen Human Brain Atlas. Based on these findings we suggest that VIT contributes to normal brain asymmetry variation. Our results can shed light on disorders associated with altered brain asymmetry. PMID- 27252637 TI - Determining Optimal Feature-Combination for LDA Classification of Functional Near Infrared Spectroscopy Signals in Brain-Computer Interface Application. AB - In this study, we determine the optimal feature-combination for classification of functional near-infrared spectroscopy (fNIRS) signals with the best accuracies for development of a two-class brain-computer interface (BCI). Using a multi channel continuous-wave imaging system, mental arithmetic signals are acquired from the prefrontal cortex of seven healthy subjects. After removing physiological noises, six oxygenated and deoxygenated hemoglobin (HbO and HbR) features-mean, slope, variance, peak, skewness and kurtosis-are calculated. All possible 2- and 3-feature combinations of the calculated features are then used to classify mental arithmetic vs. rest using linear discriminant analysis (LDA). It is found that the combinations containing mean and peak values yielded significantly higher (p < 0.05) classification accuracies for both HbO and HbR than did all of the other combinations, across all of the subjects. These results demonstrate the feasibility of achieving high classification accuracies using mean and peak values of HbO and HbR as features for classification of mental arithmetic vs. rest for a two-class BCI. PMID- 27252638 TI - The Functional Role of Neural Oscillations in Non-Verbal Emotional Communication. AB - Effective interpersonal communication depends on the ability to perceive and interpret nonverbal emotional expressions from multiple sensory modalities. Current theoretical models propose that visual and auditory emotion perception involves a network of brain regions including the primary sensory cortices, the superior temporal sulcus (STS), and orbitofrontal cortex (OFC). However, relatively little is known about how the dynamic interplay between these regions gives rise to the perception of emotions. In recent years, there has been increasing recognition of the importance of neural oscillations in mediating neural communication within and between functional neural networks. Here we review studies investigating changes in oscillatory activity during the perception of visual, auditory, and audiovisual emotional expressions, and aim to characterize the functional role of neural oscillations in nonverbal emotion perception. Findings from the reviewed literature suggest that theta band oscillations most consistently differentiate between emotional and neutral expressions. While early theta synchronization appears to reflect the initial encoding of emotionally salient sensory information, later fronto-central theta synchronization may reflect the further integration of sensory information with internal representations. Additionally, gamma synchronization reflects facilitated sensory binding of emotional expressions within regions such as the OFC, STS, and, potentially, the amygdala. However, the evidence is more ambiguous when it comes to the role of oscillations within the alpha and beta frequencies, which vary as a function of modality (or modalities), presence or absence of predictive information, and attentional or task demands. Thus, the synchronization of neural oscillations within specific frequency bands mediates the rapid detection, integration, and evaluation of emotional expressions. Moreover, the functional coupling of oscillatory activity across multiples frequency bands supports a predictive coding model of multisensory emotion perception in which emotional facial and body expressions facilitate the processing of emotional vocalizations. PMID- 27252639 TI - High Working Memory Load Impairs Language Processing during a Simulated Piloting Task: An ERP and Pupillometry Study. AB - Given the important amount of visual and auditory linguistic information that pilots have to process, operating an aircraft generates a high working-memory load (WML). In this context, the ability to focus attention on relevant information and to remain responsive to concurrent stimuli might be altered. Consequently, understanding the effects of WML on the processing of both linguistic targets and distractors is of particular interest in the study of pilot performance. In the present work, participants performed a simplified piloting task in which they had to follow one of three colored aircraft, according to specific written instructions (i.e., the written word for the color corresponding to the color of one of the aircraft) and to ignore either congruent or incongruent concurrent auditory distractors (i.e., a spoken name of color). The WML was manipulated with an n-back sub-task. Participants were instructed to apply the current written instruction in the low WML condition, and the 2-back written instruction in the high WML condition. Electrophysiological results revealed a major effect of WML at behavioral (i.e., decline of piloting performance), electrophysiological, and autonomic levels (i.e., greater pupil diameter). Increased WML consumed resources that could not be allocated to the processing of the linguistic stimuli, as indexed by lower P300/P600 amplitudes. Also, significantly, lower P600 responses were measured in incongruent vs. congruent trials in the low WML condition, showing a higher difficulty reorienting attention toward the written instruction, but this effect was canceled in the high WML condition. This suppression of interference in the high load condition is in line with the engagement/distraction trade-off model. We propose that P300/P600 components could be reliable indicators of WML and that they allow an estimation of its impact on the processing of linguistic stimuli. PMID- 27252640 TI - Saccadic Adaptation in 10-41 Month-Old Children. AB - When saccade amplitude becomes systematically inaccurate, adaptation mechanisms gradually decrease or increase it until accurate saccade targeting is recovered. Adaptive shortening and adaptive lengthening of saccade amplitude rely on separate mechanisms in adults. When these adaptation mechanisms emerge during development is poorly known except that adaptive shortening processes are functional in children above 8 years of age. Yet, saccades in infants are consistently inaccurate (hypometric) as if adaptation mechanisms were not fully functional in early childhood. Here, we tested reactive saccade adaptation in 10 41 month-old children compared to a group of 20-30 year-old adults. A visual target representing a cartoon character appeared at successive and unpredictable locations 10 degrees apart on a computer screen. During the eye movement toward the target, it systematically stepped in the direction opposite to the saccade to induce an adaptive shortening of saccade amplitude (Experiment 1). In Experiment 2, the target stepped in the same direction as the ongoing saccade to induce an adaptive lengthening of saccade amplitude. In both backward and forward adaptation experiments, saccade adaptation was compared to a control condition where there was no intrasaccadic target step. Analysis of baseline performance revealed both longer saccade reaction times and hypometric saccades in children compared to adults. In both experiments, children on average showed gradual changes in saccade amplitude consistent with the systematic intrasaccadic target steps. Moreover, the amount of amplitude change was similar between children and adults for both backward and forward adaptation. Finally, adaptation abilities in our child group were not related to age. Overall the results suggest that the neural mechanisms underlying reactive saccade adaptation are in place early during development. PMID- 27252642 TI - Sustained Aftereffect of alpha-tACS Lasts Up to 70 min after Stimulation. AB - Transcranial alternating current stimulation (tACS) has been repeatedly demonstrated to increase power of endogenous brain oscillations in the range of the stimulated frequency after stimulation. In the alpha band this aftereffect has been shown to persist for at least 30 min. However, in most experiments the aftereffect exceeded the duration of the measurement. Thus, it remains unclear how the effect develops beyond these 30 min and when it decays. The current study aimed to extend existing findings by monitoring the physiological aftereffect of tACS in the alpha range for an extended period of 90 min post-stimulation. To this end participants received either 20 min of tACS or sham stimulation with intensities below their individual sensation threshold at the individual alpha frequency (IAF). Electroencephalogram (EEG) was acquired during 3 min before and 90 min after stimulation. Subjects performed a visual vigilance task during the whole measurement. While the enhanced power in the individual alpha band did not return back to pre-stimulation baseline in the stimulation group, the difference between stimulation and sham diminishes after 70 min due to a natural alpha increase of the sham group. PMID- 27252641 TI - Music Performance As an Experimental Approach to Hyperscanning Studies. AB - Humans are fundamentally social and tend to create emergent organizations when interacting with each other; from dyads to families, small groups, large groups, societies, and civilizations. The study of the neuronal substrate of human social behavior is currently gaining momentum in the young field of social neuroscience. Hyperscanning is a neuroimaging technique by which we can study two or more brains simultaneously while participants interact with each other. The aim of this article is to discuss several factors that we deem important in designing hyperscanning experiments. We first review hyperscanning studies performed by means of electroencephalography (EEG) that have been relying on a continuous interaction paradigm. Then, we provide arguments for favoring ecological paradigms, for studying the emotional component of social interactions and for performing longitudinal studies, the last two aspects being largely neglected so far in the hyperscanning literature despite their paramount importance in social sciences. Based on these premises, we argue that music performance is a suitable experimental setting for hyperscanning and that for such studies EEG is an appropriate choice as neuroimaging modality. PMID- 27252643 TI - Synergy of AMPA and NMDA Receptor Currents in Dopaminergic Neurons: A Modeling Study. AB - Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency. PMID- 27252644 TI - Dependence of Nociceptive Detection Thresholds on Physiological Parameters and Capsaicin-Induced Neuroplasticity: A Computational Study. AB - Physiological properties of peripheral and central nociceptive subsystems can be altered over time due to medical interventions. The effective change for the whole nociceptive system can be reflected in changes of psychophysical characteristics, e.g., detection thresholds. However, it is challenging to separate contributions of distinct altered mechanisms with measurements of thresholds only. Here, we aim to understand how these alterations affect Adelta fiber-mediated nociceptive detection of electrocutaneous stimuli. First, with a neurophysiology-based model, we study the effects of single-model parameters on detection thresholds. Second, we derive an expression of model parameters determining the functional relationship between detection thresholds and the interpulse interval for double-pulse stimuli. Third, in a case study with topical capsaicin treatment, we translate neuroplasticity into plausible changes of model parameters. Model simulations qualitatively agree with changes in experimental detection thresholds. The simulations with individual forms of neuroplasticity confirm that nerve degeneration is the dominant mechanism for capsaicin-induced increases in detection thresholds. In addition, our study suggests that capsaicin induced central plasticity may last at least 1 month. PMID- 27252645 TI - The Active and Periactive Zone Organization and the Functional Properties of Small and Large Synapses. AB - The arrival of an action potential (AP) at a synaptic terminal elicits highly synchronized quanta release. Repetitive APs produce successive synaptic vesicle (SV) fusions that require management of spent SV components in the presynaptic membrane with minimum disturbance of the secretory apparatus. To this end, the synaptic machinery is structured accordingly to the strength and the range of frequencies at which each particular synapse operates. This results in variations in the number and dimension of Active Zones (AZs), amount and distribution of SVs, and probably, in the primary endocytic mechanisms they use. Understanding better how these structural differences determine the functional response in each case has been a matter of long-term interest. Here we review the structural and functional properties of three distinct types of synapses: the neuromuscular junction (NMJ; a giant, highly reliable synapse that must exocytose a large number of quanta with each stimulus to guarantee excitation of the postsynaptic cell), the hippocampal excitatory small synapse (which most often has a single release site and a relatively small pool of vesicles), and the cerebellar mossy fiber-granule cell synapse (which possesses hundreds of release sites and is able to translocate, dock and prime vesicles at high speed). We will focus on how the release apparatus is organized in each case, the relative amount of vesicular membrane that needs to be accommodated within the periAZ upon stimulation, the different mechanisms for retrieving the excess of membrane and finally, how these factors may influence the functioning of the release sites. PMID- 27252646 TI - The Shank3 Interaction Partner ProSAPiP1 Regulates Postsynaptic SPAR Levels and the Maturation of Dendritic Spines in Hippocampal Neurons. AB - The postsynaptic density or PSD is a submembranous compartment containing a wide array of proteins that contribute to both morphology and function of excitatory glutamatergic synapses. In this study, we have analyzed functional aspects of the Fezzin ProSAP-interacting protein 1 (ProSAPiP1), an interaction partner of the well-known PSD proteins Shank3 and SPAR. Using lentiviral-mediated overexpression and knockdown of ProSAPiP1, we found that this protein is dispensable for the formation of both pre- and postsynaptic specializations per se. We further show that ProSAPiP1 regulates SPAR levels at the PSD and the maturation of dendritic spines. In line with previous findings on the ProSAPiP1 homolog PSD-Zip70, we conclude that Fezzins essentially contribute to the maturation of excitatory spine synapses. PMID- 27252647 TI - In Alzheimer's Disease, 6-Month Treatment with GLP-1 Analog Prevents Decline of Brain Glucose Metabolism: Randomized, Placebo-Controlled, Double-Blind Clinical Trial. AB - In animal models, the incretin hormone GLP-1 affects Alzheimer's disease (AD). We hypothesized that treatment with GLP-1 or an analog of GLP-1 would prevent accumulation of Abeta and raise, or prevent decline of, glucose metabolism (CMRglc) in AD. In this 26-week trial, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Abeta load in brain with tracer [(11)C]PIB (PIB), CMRglc with [(18)F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P >= 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means in precuneus (P = 0.009, 3.2 MUmol/hg/min, 95% CI: 5.45; 0.92), and in parietal (P = 0.04, 2.1 MUmol/hg/min, 95% CI: 4.21; 0.081), temporal (P = 0.046, 1.54 MUmol/hg/min, 95% CI: 3.05; 0.030), and occipital (P = 0.009, 2.10 MUmol/hg/min, 95% CI: 3.61; 0.59) lobes, and in cerebellum (P = 0.04, 1.54 MUmol/hg/min, 95% CI: 3.01; 0.064). In contrast, the GLP-1 analog treatment caused a numerical but insignificant increase of CMRglc after 6 months. Cognitive scores did not change. We conclude that the GLP-1 analog treatment prevented the decline of CMRglc that signifies cognitive impairment, synaptic dysfunction, and disease evolution. We draw no firm conclusions from the Abeta load or cognition measures, for which the study was underpowered. PMID- 27252649 TI - Cortical Thickness Changes Correlate with Cognition Changes after Cognitive Training: Evidence from a Chinese Community Study. AB - The aim of this study was to investigate whether changes in cortical thickness correlated with cognitive function changes in healthy older adults after receiving cognitive training interventions. Moreover, it also aimed to examine the differential impacts of a multi-domain and a single-domain cognitive training interventions. Longitudinal magnetic resonance imaging (MRI) scanning was performed on participants 65-75 years of age using the Siemens 3.0 T Trio Tim with the Magnetization Prepared Rapid Gradient Echo (MPRAGE) sequence. The cortical thickness was determined using FreeSurfer Software. Cognitive functioning was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were significant group * time interaction effects on the left supramarginal, the left frontal pole cortical regions; and a marginal significant group * time interaction effects on visuospatial/constructional and delayed memory scores. In a multi-domain cognitive training group, a number of cortical region changes were significantly positively correlated with changes in attention, delayed memory, and the total score, but significantly negatively correlated with changes in immediate memory and language scores. In the single-domain cognitive training group, some cortical region changes were significantly positively associated with changes in immediate memory, delayed memory, and the total score, while they were significantly negatively associated with changes in visuospatial/constructional, language, and attention scores. Overall, multi-domain cognitive training offered more advantages in visuospatial/constructional, attention, and delayed memory abilities, while single-domain cognitive training benefited immediate memory ability more effectively. These findings suggest that healthy older adults benefit more from the multi-domain cognitive training than single-domain cognitive training. Cognitive training has impacted on cortical thickness changes in healthy elderly. PMID- 27252648 TI - AMD Genetics in India: The Missing Links. AB - Age related macular degeneration is a disease which occurs in aged individuals. There are various changes that occur at the cellular, molecular and physiological level with advancing age (Samiec et al., 1988; Sharma K. et al., 2014). Drusen deposition between retinal pigment epithelium (RPE) and Bruch's membrane (BM) is one of the key features in AMD patients (Mullins et al., 2000; Hageman et al., 2001) similar to Abeta/tau aggregates in Alzheimer's disease (AD) patients. The primary goal of this review is to discuss whether the various candidate genes and associated biomarkers, that are known to play an independent role in progression of AMD, exert deleterious effect on phenotype, alone or in combination, in Indian AMD patients from the same ethnic group and the significance of such research. A statistical model for probable interaction between genes could be derived from such analysis. Therefore, one can use multiple modalities to identify and enrol AMD patients based on established clinical criteria and examine the risk factors to determine if these genes are associated with risk factors, biomarkers or disease by Mendelian randomization. Similarly, there are large numbers of single nucleotide polymorphisms (SNPs) identified in human population. Even non synonymous SNPs (nsSNPs) are believed to induce deleterious effects on the functionality of various proteins. The study of such snSNPs could provide a better genetic insight for diverse phenotypes of AMD patients, predicting significant risk factors for the disease in Indian population. Therefore, the prediction of biological effect of nsSNPs in the candidate genes and the associated grant applications in the subject are highly solicited.Therefore, genotyping and levels of protein expression of various genes would provide wider canvas in genetic complexity of AMD pathology which should be evaluated by valid statistical and bioinformatics' tools. Longitudinal follow up of Indian AMD patients to evaluate the temporal effect of SNPs and biomarkers on progression of disease would provide a unique strategy in the field. PMID- 27252650 TI - Phytoestrogen Bakuchiol Exhibits In Vitro and In Vivo Anti-breast Cancer Effects by Inducing S Phase Arrest and Apoptosis. AB - Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae). The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well-studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP) dose dependently (0-1 MUg/ml), demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 MUg/ml) induced the cell proliferation and ERalpha expression in MCF-7 cells, which could be blocked by the anti-estrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 MUg/ml) inhibited breast cancer cell growth, with a stronger anti-proliferative effect than resveratrol, a widely studied analog of bakuchiol. High doses of bakuchiol (4, 7, and 10 MUg/ml) were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERbeta expression and suppressed ERalpha expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15), Myt1, P-Wee1 (Ser642), p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce apoptosis via intrinsic apoptotic pathway. The in vivo anti-breast cancer effect of bakuchiol was further proved in zebrafish (Danio rerio, wild-type AB) xenografts. 0.5 MUg/ml of bakuchiol significantly reduced the MCF-7 cell mass in zebrafish xenografts. Overall, these results suggested the potential of using bakuchiol in HRT and breast cancer treatment. PMID- 27252651 TI - Immuno-Positron Emission Tomography with Zirconium-89-Labeled Monoclonal Antibodies in Oncology: What Can We Learn from Initial Clinical Trials? AB - Selection of the right drug for the right patient is a promising approach to increase clinical benefit of targeted therapy with monoclonal antibodies (mAbs). Assessment of in vivo biodistribution and tumor targeting of mAbs to predict toxicity and efficacy is expected to guide individualized treatment and drug development. Molecular imaging with positron emission tomography (PET) using zirconium-89 ((89)Zr)-labeled monoclonal antibodies also known as (89)Zr-immuno PET, visualizes and quantifies uptake of radiolabeled mAbs. This technique provides a potential imaging biomarker to assess target expression, as well as tumor targeting of mAbs. In this review we summarize results from initial clinical trials with (89)Zr-immuno-PET in oncology and discuss technical aspects of trial design. In clinical trials with (89)Zr-immuno-PET two requirements should be met for each (89)Zr-labeled mAb to realize its full potential. One requirement is that the biodistribution of the (89)Zr-labeled mAb (imaging dose) reflects the biodistribution of the drug during treatment (therapeutic dose). Another requirement is that tumor uptake of (89)Zr-mAb on PET is primarily driven by specific, antigen-mediated, tumor targeting. Initial trials have contributed toward the development of (89)Zr-immuno-PET as an imaging biomarker by showing correlation between uptake of (89)Zr-labeled mAbs on PET and target expression levels in biopsies. These results indicate that (89)Zr-immuno-PET reflects specific, antigen-mediated binding. (89)Zr-immuno-PET was shown to predict toxicity of RIT, but thus far results indicating that toxicity of mAbs or mAb drug conjugate treatment can be predicted are lacking. So far, one study has shown that molecular imaging combined with early response assessment is able to predict response to treatment with the antibody-drug conjugate trastuzumab emtansine, in patients with human epithelial growth factor-2 (HER2)-positive breast cancer. Future studies would benefit from a standardized criterion to define positive tumor uptake, possibly supported by quantitative analysis, and validated by linking imaging data with corresponding clinical outcome. Taken together, these results encourage further studies to develop (89)Zr-immuno-PET as a predictive imaging biomarker to guide individualized treatment, as well as for potential application in drug development. PMID- 27252652 TI - Bioabsorbable Bypass Grafts Biofunctionalised with RGD Have Enhanced Biophysical Properties and Endothelialisation Tested In vivo. AB - Small diameter arterial bypass grafts are considered as unmet clinical need since the current grafts have poor patency of 25% within 5 years. We have developed a 3D scaffold manufactured from natural and synthetic biodegradable polymers, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(??-caprolactone) (PCL), respectively. Further to improve the biophysical properties as well as endothelialisation, the grafts were covalently conjugated with arginine-glycine aspartic acid (RGD) bioactive peptides. The biophysical properties as well as endothelialisation of PHBV/PCL and PCL 2 mm diameter bypass grafts were assessed with and without biofunctionalisation with RGD peptides in vitro and in vivo. Morphology of the grafts was assessed by scanning electron microscopy, whereas physico-mechanical properties were evaluated using a physiological circulating system equipped with a state of art ultrasound vascular wall tracking system. Endothelialisation of the grafts in vitro and in vivo were assessed using a cell viability assay and rat abdominal aorta replacement model, respectively. The biofunctionalisation with RGD bioactive peptides decreased mean fiber diameter and mean pore area in PHBV/PCL grafts; however, this was not the case for PCL grafts. Both PHBV/PCL and PCL grafts with RGD peptides had lower durability compared to those without; these durability values were similar to those of internal mammary artery. Modification of PHBV/PCL and PCL grafts with RGD peptides increased endothelial cell viability in vitro by a factor of eight and enhanced the formation of an endothelial cell monolayer in vivo 1 month postimplantation. In conclusion, PHBV/PCL small-caliber graft can be a suitable 3D scaffold for the development of a tissue engineering arterial bypass graft. PMID- 27252654 TI - Pelleted Bone Marrow Derived Mesenchymal Stem Cells Are Better Protected from the Deleterious Effects of Arthroscopic Heat Shock. AB - INTRODUCTION: The impact of arthroscopic temperature on joint tissues is poorly understood and it is not known how mesenchymal stem cells (MSCs) respond to the effects of heat generated by the device during the process of arthroscopy assisted experimental cell-based therapy. In the present study, we isolated and phenotypically characterized human bone marrow mesenchymal stem cells (hBMMSCs) from osteoarthritis (OA) patients, and evaluated the effect of arthroscopic heat on cells in suspension and pellet cultures. METHODS: Primary cultures of hBMMSCs were isolated from bone marrow aspirates of OA patients and cultured using DMEM supplemented with 10% FBS and characterized for their stemness. hBMMSCs (1 * 10(6) cells) cultured as single cell suspensions or cell pellets were exposed to an illuminated arthroscope for 10, 20, or 30 min. This was followed by analysis of cellular proliferation and heat shock related gene expression. RESULTS: hBMMSCs were viable and exhibited population doubling, short spindle morphology, MSC related CD surface markers expression and tri-lineage differentiation into adipocytes, chondrocytes and osteoblasts. Chondrogenic and osteogenic differentiation increased collagen production and alkaline phosphatase activity. Exposure of hBMMSCs to an illuminated arthroscope for 10, 20, or 30 min for 72 h decreased metabolic activity of the cells in suspensions (63.27% at 30 min) and increased metabolic activity in cell pellets (62.86% at 10 min and 68.57% at 20 min). hBMMSCs exposed to 37, 45, and 55 degrees C for 120 s demonstrated significant upregulation of BAX, P53, Cyclin A2, Cyclin E1, TNF-alpha, and HSP70 in cell suspensions compared to cell pellets. CONCLUSIONS: hBMMSC cell pellets are better protected from temperature alterations compared to cell suspensions. Transplantation of hBMMSCs as pellets rather than as cell suspensions to the cartilage defect site would therefore support their viability and may aid enhanced cartilage regeneration. PMID- 27252655 TI - Cardiac Morphology and Function, and Blood Gas Transport in Aquaporin-1 Knockout Mice. AB - We have studied cardiac and respiratory functions of aquaporin-1-deficient mice by the Pressure-Volume-loop technique and by blood gas analysis. In addition, the morphological properties of the animals' hearts were analyzed. In anesthesia under maximal dobutamine stimulation, the mice exhibit a moderately elevated heart rate of < 600 min(-1) and an O2 consumption of ~0.6 ml/min/g, which is about twice the basal rate. In this state, which is similar to the resting state of the conscious animal, all cardiac functions including stroke volume and cardiac output exhibited resting values and were identical between deficient and wildtype animals. Likewise, pulmonary and peripheral exchange of O2 and CO2 were normal. In contrast, several morphological parameters of the heart tissue of deficient mice were altered: (1) left ventricular wall thickness was reduced by 12%, (2) left ventricular mass, normalized to tibia length, was reduced by 10 20%, (3) cardiac muscle fiber cross sectional area was decreased by 17%, and (4) capillary density was diminished by 10%. As the P-V-loop technique yielded normal end-diastolic and end-systolic left ventricular volumes, the deficient hearts are characterized by thin ventricular walls in combination with normal intraventricular volumes. The aquaporin-1-deficient heart thus seems to be at a disadvantage compared to the wild-type heart by a reduced left-ventricular wall thickness and an increased diffusion distance between blood capillaries and muscle mitochondria. While under the present quasi-resting conditions these morphological alterations have no consequences for cardiac function, we expect that the deficient hearts will show a reduced maximal cardiac output. PMID- 27252656 TI - Metabolomic Analysis in Brain Research: Opportunities and Challenges. AB - Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s). Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results. PMID- 27252657 TI - Community Structure Reveals Biologically Functional Modules in MEF2C Transcriptional Regulatory Network. AB - Gene regulatory networks are useful to understand the activity behind the complex mechanisms in transcriptional regulation. A main goal in contemporary biology is using such networks to understand the systemic regulation of gene expression. In this work, we carried out a systematic study of a transcriptional regulatory network derived from a comprehensive selection of all potential transcription factor interactions downstream from MEF2C, a human transcription factor master regulator. By analyzing the connectivity structure of such network, we were able to find different biologically functional processes and specific biochemical pathways statistically enriched in communities of genes into the network, such processes are related to cell signaling, cell cycle and metabolism. In this way we further support the hypothesis that structural properties of biological networks encode an important part of their functional behavior in eukaryotic cells. PMID- 27252653 TI - Specialized Functional Diversity and Interactions of the Na,K-ATPase. AB - Na,K-ATPase is a protein ubiquitously expressed in the plasma membrane of all animal cells and vitally essential for their functions. A specialized functional diversity of the Na,K-ATPase isozymes is provided by molecular heterogeneity, distinct subcellular localizations, and functional interactions with molecular environment. Studies over the last decades clearly demonstrated complex and isoform-specific reciprocal functional interactions between the Na,K-ATPase and neighboring proteins and lipids. These interactions are enabled by a spatially restricted ion homeostasis, direct protein-protein/lipid interactions, and protein kinase signaling pathways. In addition to its "classical" function in ion translocation, the Na,K-ATPase is now considered as one of the most important signaling molecules in neuronal, epithelial, skeletal, cardiac and vascular tissues. Accordingly, the Na,K-ATPase forms specialized sub-cellular multimolecular microdomains which act as receptors to circulating endogenous cardiotonic steroids (CTS) triggering a number of signaling pathways. Changes in these endogenous cardiotonic steroid levels and initiated signaling responses have significant adaptive values for tissues and whole organisms under numerous physiological and pathophysiological conditions. This review discusses recent progress in the studies of functional interactions between the Na,K-ATPase and molecular microenvironment, the Na,K-ATPase-dependent signaling pathways and their significance for diversity of cell function. PMID- 27252658 TI - beta-Cyclodextrins Decrease Cholesterol Release and ABC-Associated Transporter Expression in Smooth Muscle Cells and Aortic Endothelial Cells. AB - Atherosclerosis is an inflammatory disease that leads to an aberrant accumulation of cholesterol in vessel walls forming atherosclerotic plaques. During this process, the mechanism regulating complex cellular cholesterol pools defined as the reverse cholesterol transport (RCT) is altered as well as expression and functionality of transporters involved in this process, namely ABCA1, ABCG1, and SR-BI. Macrophages, arterial endothelial and smooth muscle cells (SMCs) have been involved in the atherosclerotic plaque formation. As macrophages are widely described as the major cell type forming the foam cells by accumulating intracellular cholesterol, RCT alterations have been poorly studied at the arterial endothelial cell and SMC levels. Amongst the therapeutics tested to actively counteract cellular cholesterol accumulation, the methylated beta cyclodextrin, KLEPTOSE(r) CRYSMEbeta, has recently shown promising effects on decreasing the atherosclerotic plaque size in atherosclerotic mouse models. Therefore we investigated in vitro the RCT process occurring in SMCs and in arterial endothelial cells (ABAE) as well as the ability of some modified beta CDs with different methylation degree to modify RCT in these cells. To this aim, cells were incubated in the presence of different methylated beta-CDs, including KLEPTOSE(r) CRYSMEbeta. Both cell types were shown to express basal levels of ABCA1 and SR-BI whereas ABCG1 was solely found in ABAE. Upon CD treatments, the percentage of membrane-extracted cholesterol correlated to the methylation degree of the CDs independently of the lipid composition of the cell membranes. Decreasing the cellular cholesterol content with CDs led to reduce the expression levels of ABCA1 and ABCG1. In addition, the cholesterol efflux to ApoA-I and HDL particles was significantly decreased suggesting that cells forming the blood vessel wall are able to counteract the CD-induced loss of cholesterol. Taken together, our observations suggest that methylated beta-CDs can significantly reduce the cellular cholesterol content of cells forming atherosclerotic lesions and can subsequently modulate the expression of ABC transporters involved in RCT. The use of methylated beta-CDs would represent a valuable and efficient tool to interfere with atherosclerosis pathogenesis in patients, nonetheless their mode of action still needs further investigations to be fully understood and finely controlled at the cellular level. PMID- 27252660 TI - In vivo Sarcomere Lengths and Sarcomere Elongations Are Not Uniform across an Intact Muscle. AB - Sarcomere lengths have been a crucial outcome measure for understanding and explaining basic muscle properties and muscle function. Sarcomere lengths for a given muscle are typically measured at a single spot, often in the mid-belly of the muscle, and at a given muscle length. It is then assumed implicitly that the sarcomere length measured at this single spot represents the sarcomere lengths at other locations within the muscle, and force-length, force-velocity, and power velocity properties of muscles are often implied based on these single sarcomere length measurements. Although, intuitively appealing, this assumption is yet to be supported by systematic evidence. The objective of this study was to measure sarcomere lengths at defined locations along and across an intact muscle, at different muscle lengths. Using second harmonic generation (SHG) imaging technique, sarcomere patterns in passive mouse tibialis anterior (TA) were imaged in a non-contact manner at five selected locations ("proximal," "distal," "middle," "medial," and "lateral" TA sites) and at three different lengths encompassing the anatomical range of motion of the TA. We showed that sarcomere lengths varied substantially within small regions of the muscle and also for different sites across the entire TA. Also, sarcomere elongations with muscle lengthening were non-uniform across the muscle, with the highest sarcomere stretches occurring near the myotendinous junction. We conclude that muscle mechanics derived from sarcomere length measured from a small region of a muscle may not well-represent the sarcomere length and associated functional properties of the entire muscle. PMID- 27252659 TI - Characterization of ATPase Activity of P2RX2 Cation Channel. AB - P2X purinergic receptors are plasma membrane ATP-dependent cation channels that are broadly distributed in the mammalian tissues. P2RX2 is a modulator of auditory sensory hair cell mechanotransduction and plays an important role in hair cell tolerance to noise. In this study, we demonstrate for the first time in vitro and in cochlear neuroepithelium, that P2RX2 possesses the ATPase activity. We observed that the P2RX2 V60L human deafness mutation alters its ability to bind ATP, while the G353R has no effect on ATP binding or hydrolysis. A non hydrolysable ATP assay using HEK293 cells suggests that ATP hydrolysis plays a significant role in the opening and gating of the P2RX2 ion channel. Moreover, the results of structural modeling of the molecule was in agreement with our experimental observations. These novel findings suggest the intrinsic ATPase activity of P2RX2 and provide molecular insights into the channel opening. PMID- 27252661 TI - Pictorial Personality Traits Questionnaire for Children (PPTQ-C)-A New Measure of Children's Personality Traits. AB - In order to adjust personality measurements to children's developmental level, we constructed the Pictorial Personality Traits Questionnaire for Children (PPTQ-C). To validate the measure, we conducted a study with a total group of 1028 children aged between 7 and 13 years old. Structural validity was established through Exploratory Structural Equation Model (ESEM). Criterion validity was confirmed with a multitrait-multimethod analysis for which we introduced the children's self-assessment scores from the Big Five Questionnaire for Children. Despite some problems with reliability, one can conclude that the PPTQ-C can be a valid instrument for measuring personality traits, particularly in a group of young children (aged ~7-10 years). PMID- 27252662 TI - Supervising and Controlling Unmanned Systems: A Multi-Phase Study with Subject Matter Experts. AB - Proliferation in the use of Unmanned Aerial Systems (UASs) in civil and military operations has presented a multitude of human factors challenges; from how to bridge the gap between demand and availability of trained operators, to how to organize and present data in meaningful ways. Utilizing the Design Research Methodology (DRM), a series of closely related studies with subject matter experts (SMEs) demonstrate how the focus of research gradually shifted from "how many systems can a single operator control" to "how to distribute missions among operators and systems in an efficient way". The first set of studies aimed to explore the modal number, i.e., how many systems can a single operator supervise and control. It was found that an experienced operator can supervise up to 15 UASs efficiently using moderate levels of automation, and control (mission and payload management) up to three systems. Once this limit was reached, a single operator's performance was compared to a team controlling the same number of systems. In general, teams led to better performances. Hence, shifting design efforts toward developing tools that support teamwork environments of multiple operators with multiple UASs (MOMU). In MOMU settings, when the tasks are similar or when areas of interest overlap, one operator seems to have an advantage over a team who needs to collaborate and coordinate. However, in all other cases, a team was advantageous over a single operator. Other findings and implications, as well as future directions for research are discussed. PMID- 27252663 TI - Development of a Brief Multicultural Version of the Test of Mobile Phone Dependence (TMDbrief) Questionnaire. AB - The Test of Mobile Phone Dependence (TMD) questionnaire (Choliz, 2012) evaluates the main features of mobile phone dependence: tolerance, abstinence syndrome, impaired impulse control, associated problems, excessive use, etc. OBJECTIVE: The objective of this study was to develop a multicultural version of the TMD (TMDbrief) adapted to suit the novel communication tools of smartphones. PROCEDURE: In this study, the TMD was completed by 2,028 young respondents in six distinct world regions: Southern Europe, Northwest Europe, South-America, Mesoamerica, Pakistan, and India. RESULTS: Psychometric analysis of the reliability of the instrument and factor analysis were performed to adapt the TMDbrief for use in these regions. Differences among regions with respect to TMD Mobile Phone Dependence scores were obtained. CONCLUSION: A brief questionnaire for the evaluation of mobile phone addiction in cross-cultural studies was successfully developed. PMID- 27252664 TI - Emotional Effects on University Choice Behavior: The Influence of Experienced Narrators and Their Characteristics. AB - This study analyzes the influence that experienced users of university resources might have as narrative sources of information for other students in the process of choosing their schools. Informative videos about the benefits of studying at the university provide a reference model. In these videos, a group of young people present their views and explain their reasons for choosing the university in which they are pursuing their degrees; the various narrators detail all the resources available. This study investigates whether the individual identifiers of these narrators (e.g., gender, age, physical appearance, nonverbal gestures such as smiling, posture) influence perceptions of the credibility of the information they provide. Among a sample of 150 students in their last year of pre-university training, the results demonstrate that the students' ability to identify with the narrators provides information and arouses emotions that inform their perceptions of reliability and therefore their consumption choices. None of these predictors appear to serve as determinants that can be generalized, but if emotional attitudes in response to narratives about the topic (i.e., the university) are positive, then they prompt a change in attitude toward that reference topic too. PMID- 27252665 TI - The Influence of Task-Irrelevant Flankers Depends on the Composition of Emotion Categories. AB - Face recognition usually takes place in a social context, where faces are surrounded by other stimuli. These can act as distracting flankers which impair recognition. Previous work has suggested that flankers expressing negative emotions distract more than positive ones. However, the various negative emotions differ in their relative impact and it is unclear whether all negative emotions are equally distracting. We investigated the impact of three negative (angry, fearful, sad) and one positive (happy) facial flanker conditions on target recognition in an emotion discrimination task. We examined the effect of the receiver's gender, and the impact of two different temporal delays between flanker and target onset, as stimulus onset asynchrony is assumed to affect distractor strength. Participants identified and rated the emotional intensity of target faces surrounded by either face (emotional and neutral) or non-face flankers. Target faces were presented either simultaneously with the flankers, or delayed by 300 ms. Contrary to our hypothesis, negative flankers did not exert stronger distraction effects than positive or neutral flankers. However, happy flankers reduced recognition performance. Results of a follow-up experiment with a balanced number of emotion categories (one positive, one negative and one neutral flanker condition) suggest that the distraction effect of emotional flankers depends on the composition of the emotion categories. Additionally, congruency effects were found to be valence-specific and overruled by threat stimuli. Females responded more quickly and rated targets in happy flankers as less intense. This indicates a gender difference in emotion processing, with greater sensitivity to facial flankers in women. Targets were rated as more intense when they were presented without a temporal delay, possibly due to a stronger flanker contrast. These three experiments show that an exceptional processing of threat-related flanker stimuli depends on emotion category composition, which should be considered a mediating factor when examining emotional context effects. PMID- 27252666 TI - Drinking Motives As Mediators of the Associations between Reinforcement Sensitivity and Alcohol Misuse and Problems. AB - Alcohol may be used and misused for different reasons, i.e., to enhance positive affect and to cope with negative affect. These to pathways are thought to depend on two distinct and relatively stable neurobiological systems: the behavioral activation (BAS; i.e., fun seeking, drive, reward responsiveness) and behavioral inhibition (BIS) systems. This study investigates the associations of BAS and BIS sensitivity with risky single-occasion drinking and alcohol use disorder in a representative sample of 5362 young Swiss men. In order to better understand the contribution of more proximal motivational factors in the associations of BIS and BAS with alcohol outcomes, mediations via drinking motives (i.e., enhancement, social, coping, conformity) was also tested. Risky single-occasion drinking and alcohol use disorder were positively associated with fun seeking and negatively with reward responsiveness. Drive was negatively associated with risky single occasion drinking. BIS was positively associated with alcohol use disorder and negatively with risky single-occasion drinking. Positive associations of fun seeking with risky single-occasion drinking and alcohol use disorder were partially mediated mainly by enhancement motives. Negative association of drive with risky single-occasion drinking was partially mediated by conformity motives. The negative reward responsiveness-alcohol use disorder association was partially mediated, whereas the negative reward responsiveness-risky single-occasion drinking association was fully mediated, mainly by coping and enhancement motives. The positive BIS-alcohol use disorder association was fully mediated mainly by coping motives. Fun seeking constitutes a risk factor, whereas drive and reward responsiveness constitute protective factors against alcohol misuse and disorder. BIS constitutes a protective factor against risky single-occasion drinking and a risk factor for alcohol use disorder. The results of the mediation analysis suggest that prevention strategies targeting coping and enhancement motives may reduce the risk associated with high BIS and with high fun seeking, respectively. PMID- 27252667 TI - Ready, Set, Go! Low Anticipatory Response during a Dyadic Task in Infants at High Familial Risk for Autism. AB - Children with autism spectrum disorder (ASD) demonstrate a host of motor impairments that may share a common developmental basis with ASD core symptoms. School-age children with ASD exhibit particular difficulty with hand-eye coordination and appear to be less sensitive to visual feedback during motor learning. Sensorimotor deficits are observable as early as 6 months of age in children who later develop ASD; yet the interplay of early motor, visual and social skill development in ASD is not well understood. Integration of visual input with motor output is vital for the formation of internal models of action. Such integration is necessary not only to master a wide range of motor skills, but also to imitate and interpret the actions of others. Thus, closer examination of the early development of visual-motor deficits is of critical importance to ASD. In the present study of infants at high risk (HR) and low risk (LR) for ASD, we examined visual-motor coupling, or action anticipation, during a dynamic, interactive ball-rolling activity. We hypothesized that, compared to LR infants, HR infants would display decreased anticipatory response (perception-guided predictive action) to the approaching ball. We also examined visual attention before and during ball rolling to determine whether attention engagement contributed to differences in anticipation. Results showed that LR and HR infants demonstrated context appropriate looking behavior, both before and during the ball's trajectory toward them. However, HR infants were less likely to exhibit context appropriate anticipatory motor response to the approaching ball (moving their arm/hand to intercept the ball) than LR infants. This finding did not appear to be driven by differences in motor skill between risk groups at 6 months of age and was extended to show an atypical predictive relationship between anticipatory behavior at 6 months and preference for looking at faces compared to objects at age 14 months in the HR group. PMID- 27252668 TI - Clarifying Associations between Childhood Adversity, Social Support, Behavioral Factors, and Mental Health, Health, and Well-Being in Adulthood: A Population Based Study. AB - Previous studies have shown that socio-demographic factors, childhood socioeconomic status (CSES), childhood traumatic experiences (CTEs), social support and behavioral factors are associated with health and well-being in adulthood. However, the relative importance of these factors for mental health, health, and well-being has not been studied. Moreover, the mechanisms by which CTEs affect mental health, health, and well-being in adulthood are not clear. Using data from a representative sample (n = 12,981) of the adult population in Tromso, Norway, this study examines (i) the relative contribution of structural conditions (gender, age, CSES, psychological abuse, physical abuse, and substance abuse distress) to social support and behavioral factors in adulthood; (ii) the relative contribution of socio-demographic factors, CSES, CTEs, social support, and behavioral factors to three multi-item instruments of mental health (SCL-10), health (EQ-5D), and subjective well-being (SWLS) in adulthood; (iii) the impact of CTEs on mental health, health, and well-being in adulthood, and; (iv) the mediating role of adult social support and behavioral factors in these associations. Instrumental support (24.16%, p < 0.001) explained most of the variation in mental health, while gender (21.32%, p < 0.001) explained most of the variation in health, and emotional support (23.34%, p < 0.001) explained most of the variation in well-being. Psychological abuse was relatively more important for mental health (12.13%), health (7.01%), and well-being (9.09%), as compared to physical abuse, and substance abuse distress. The subjective assessment of childhood financial conditions was relatively more important for mental health (6.02%), health (10.60%), and well-being (20.60%), as compared to mother's and father's education. CTEs were relatively more important for mental health, while, CSES was relatively more important for health and well-being. Respondents exposed to all three types of CTEs had a more than two-fold increased risk of being mentally unhealthy (RR Total Effect = 2.75, 95% CI: 2.19-3.10), an 89% increased risk of being unhealthy (RR Total Effect = 1.89, 95% CI: 1.47-1.99), and a 42% increased risk of having a low level of well-being in adulthood (RR Total Effect = 1.42, 95% CI: 1.29-1.52). Social support and behavioral factors mediate 11-18% (p < 0.01) of these effects. The study advances the theoretical understanding of how CTEs influence adult mental health, health, and well-being. PMID- 27252669 TI - Chromatic Perceptual Learning but No Category Effects without Linguistic Input. AB - Perceptual learning involves an improvement in perceptual judgment with practice, which is often specific to stimulus or task factors. Perceptual learning has been shown on a range of visual tasks but very little research has explored chromatic perceptual learning. Here, we use two low level perceptual threshold tasks and a supra-threshold target detection task to assess chromatic perceptual learning and category effects. Experiment 1 investigates whether chromatic thresholds reduce as a result of training and at what level of analysis learning effects occur. Experiment 2 explores the effect of category training on chromatic thresholds, whether training of this nature is category specific and whether it can induce categorical responding. Experiment 3 investigates the effect of category training on a higher level, lateralized target detection task, previously found to be sensitive to category effects. The findings indicate that performance on a perceptual threshold task improves following training but improvements do not transfer across retinal location or hue. Therefore, chromatic perceptual learning is category specific and can occur at relatively early stages of visual analysis. Additionally, category training does not induce category effects on a low level perceptual threshold task, as indicated by comparable discrimination thresholds at the newly learned hue boundary and adjacent test points. However, category training does induce emerging category effects on a supra-threshold target detection task. Whilst chromatic perceptual learning is possible, learnt category effects appear to be a product of left hemisphere processing, and may require the input of higher level linguistic coding processes in order to manifest. PMID- 27252670 TI - Implicit and Explicit Learning of a Sequential Postural Weight-Shifting Task in Young and Older Adults. AB - Sequence-specific postural motor learning in a target-directed weight-shifting task in 12 older and 12 young participants was assessed. In the implicit sequence learning condition participants performed a concurrent spatial cognitive task and in the two explicit conditions participants were required to discover the sequence order either with or without the concurrent cognitive task. Participants moved a cursor on the screen from the center location to one of the target locations projected in a semi-circle and back by shifting their center of pressure (CoP) on force plates. During the training the targets appeared in a simple fixed 5-target sequence. Plan-based control (i.e., direction of the CoP displacement in the first part of the target-directed movement) improved by anticipating the sequence order in the implicit condition but not in the explicit dual task condition. Only the young participants were able to use the explicit knowledge of the sequence structure to improve the directional error as indicated by a significant decrease in directional error over practice and an increase in directional error with sequence removal in the explicit single task condition. Time spent in the second part of the movement trajectory to stabilize the cursor on the target location improved over training in both the implicit and explicit sequence learning conditions, for both age groups. These results might indicate that an implicit motor learning method, which holds back explicit awareness of task relevant features, may be desirable for improving plan-based motor control in older adults. PMID- 27252671 TI - Monitoring Alpha Oscillations and Pupil Dilation across a Performance-Intensity Function. AB - Listening to degraded speech can be challenging and requires a continuous investment of cognitive resources, which is more challenging for those with hearing loss. However, while alpha power (8-12 Hz) and pupil dilation have been suggested as objective correlates of listening effort, it is not clear whether they assess the same cognitive processes involved, or other sensory and/or neurophysiological mechanisms that are associated with the task. Therefore, the aim of this study is to compare alpha power and pupil dilation during a sentence recognition task in 15 randomized levels of noise (-7 to +7 dB SNR) using highly intelligible (16 channel vocoded) and moderately intelligible (6 channel vocoded) speech. Twenty young normal-hearing adults participated in the study, however, due to extraneous noise, data from only 16 (10 females, 6 males; aged 19-28 years) was used in the Electroencephalography (EEG) analysis and 10 in the pupil analysis. Behavioral testing of perceived effort and speech performance was assessed at 3 fixed SNRs per participant and was comparable to sentence recognition performance assessed in the physiological test session for both 16- and 6-channel vocoded sentences. Results showed a significant interaction between channel vocoding for both the alpha power and the pupil size changes. While both measures significantly decreased with more positive SNRs for the 16-channel vocoding, this was not observed with the 6-channel vocoding. The results of this study suggest that these measures may encode different processes involved in speech perception, which show similar trends for highly intelligible speech, but diverge for more spectrally degraded speech. The results to date suggest that these objective correlates of listening effort, and the cognitive processes involved in listening effort, are not yet sufficiently well understood to be used within a clinical setting. PMID- 27252672 TI - Multilevel Modeling and Policy Development: Guidelines and Applications to Medical Travel. AB - Medical travel has expanded rapidly in recent years, resulting in new markets and increased access to medical care. Whereas several studies investigated the motives of individuals seeking healthcare abroad, the conventional analytical approach is limited by substantial caveats. Classical techniques as found in the literature cannot provide sufficient insight due to the nested nature of data generated. The application of adequate analytical techniques, specifically multilevel modeling, is scarce to non-existent in the context of medical travel. This study introduces the guidelines for application of multilevel techniques in public health research by presenting an application of multilevel modeling in analyzing the decision-making patterns of potential medical travelers. Benefits and potential limitations are discussed. PMID- 27252673 TI - Combat PTSD and Implicit Behavioral Tendencies for Positive Affective Stimuli: A Brief Report. AB - BACKGROUND: Prior cognitive research in posttraumatic stress disorder (PTSD) has focused on automatic responses to negative affective stimuli, including attentional facilitation or disengagement and avoidance action tendencies. More recent research suggests PTSD may also relate to differences in reward processing, which has lead to theories of PTSD relating to approach-avoidance imbalances. The current pilot study assessed how combat-PTSD symptoms relate to automatic behavioral tendencies to both positive and negative affective stimuli. METHOD: Twenty male combat veterans completed the approach-avoidance task (AAT), Clinician Administered PTSD Scale, Beck Depression Inventory-II, and State-Trait Anger Expression Inventory-II. During the AAT, subjects pulled (approach) or pushed (avoid) a joystick in response to neutral, happy, disgust, and angry faces based on border color. Bias scores were calculated for each emotion type (avoid approach response latency differences). Main and interaction effects for psychological symptom severity and emotion type on bias score were assessed using linear mixed models. RESULTS: There was a significant interaction between PTSD symptoms and emotion type, driven primarily by worse symptoms relating to a greater bias to avoid happy faces. Post hoc tests revealed that veterans with worse PTSD symptoms were slower to approach as well as quicker to avoid happy faces. Neither depressive nor anger symptoms related to avoid or approach tendencies of emotional stimuli. CONCLUSION: Posttraumatic stress disorder severity was associated with a bias for avoiding positive affective stimuli. These results provide further evidence that PTSD may relate to aberrant processing of positively valenced, or rewarding stimuli. Implicit responses to rewarding stimuli could be an important factor in PTSD pathology and treatment. Specifically, these findings have implications for recent endeavors in using computer-based interventions to influence automatic approach-avoidance tendencies. PMID- 27252674 TI - Goodbye or Identify: Detrimental Effects of Downsizing on Identification and Survivor Performance. AB - Research shows that after layoffs, employees often report decreased commitment and performance which has been coined the survivor syndrome. However, the mechanisms underlying this effect remain underexplored. The purpose of the paper is to show that reduced organizational identification can serve as an explanation for the survivor syndrome. We conducted a laboratory experiment, in which participants work as a group of employees for another participant who acts as employer. In the course of the experiment, the employer decides whether one of his or her employees should be laid off or not. Mediation analysis supports a social identity-based explanation for the emergence of the survivor syndrome: downsizing causes lower identification with the employer which in turn relates to lower performance of employees. PMID- 27252675 TI - Predicting Children's Reading and Mathematics Achievement from Early Quantitative Knowledge and Domain-General Cognitive Abilities. AB - One hundred children (44 boys) participated in a 3-year longitudinal study of the development of basic quantitative competencies and the relation between these competencies and later mathematics and reading achievement. The children's preliteracy knowledge, intelligence, executive functions, and parental educational background were also assessed. The quantitative tasks assessed a broad range of symbolic and nonsymbolic knowledge and were administered four times across 2 years of preschool. Mathematics achievement was assessed at the end of each of 2 years of preschool, and mathematics and word reading achievement were assessed at the end of kindergarten. Our goals were to determine how domain general abilities contribute to growth in children's quantitative knowledge and to determine how domain-general and domain-specific abilities contribute to children's preschool mathematics achievement and kindergarten mathematics and reading achievement. We first identified four core quantitative competencies (e.g., knowledge of the cardinal value of number words) that predict later mathematics achievement. The domain-general abilities were then used to predict growth in these competencies across 2 years of preschool, and the combination of domain-general abilities, preliteracy skills, and core quantitative competencies were used to predict mathematics achievement across preschool and mathematics and word reading achievement at the end of kindergarten. Both intelligence and executive functions predicted growth in the four quantitative competencies, especially across the first year of preschool. A combination of domain-general and domain-specific competencies predicted preschoolers' mathematics achievement, with a trend for domain-specific skills to be more strongly related to achievement at the beginning of preschool than at the end of preschool. Preschool preliteracy skills, sensitivity to the relative quantities of collections of objects, and cardinal knowledge predicted reading and mathematics achievement at the end of kindergarten. Preliteracy skills were more strongly related to word reading, whereas sensitivity to relative quantity was more strongly related to mathematics achievement. The overall results indicate that a combination of domain-general and domain-specific abilities contribute to development of children's early mathematics and reading achievement. PMID- 27252676 TI - Editorial: Evolutionary Theory: Fringe or Central to Psychological Science. PMID- 27252677 TI - Expertise and the Interaction between Different Perceptual-Cognitive Skills: Implications for Testing and Training. PMID- 27252678 TI - Sequence Effect in Parkinson's Disease Is Related to Motor Energetic Cost. AB - Bradykinesia is the most disabling motor symptom of Parkinson's disease (PD). The sequence effect (SE), a feature of bradykinesia, refers to the rapid decrement in amplitude and speed of repetitive movements (e.g., gait, handwriting) and is a major cause of morbidity in PD. Previous research has revealed mixed results regarding the role of dopaminergic treatment in the SE. However, external cueing has been shown to improve it. In this study, we aimed to characterize the SE systematically and relate this phenomenon to the energetic cost of movement within the context of cost-benefit framework of motor control. We used a dynamic isometric motor task with auditory pacing to assess the SE in motor output during a 15-s task segment in PD patients and matched controls. All participants performed the task with both hands, and without and with visual feedback (VF). Patients were also tested in "on"- and "off"-dopaminergic states. Patients in the "off" state did not show higher SE compared to controls, partly due to large variance in their performance. However, patients in the "on" state and in the absence of VF showed significantly higher SE compared to controls. Patients expended higher total motor energy compared to controls in all conditions and regardless of their medication status. In this experimental situation, the SE in PD is associated with the cumulative energetic cost of movement. Dopaminergic treatment, critical for internal triggering of movement, fails to maintain the motor vigor across responses. The high motor cost may be related to failure to incorporate limbic/motivational cues into the motor plan. VF may facilitate performance by shifting the driving of movement from internal to external or, alternatively, by functioning as a motivational cue. PMID- 27252679 TI - Resveratrol Ameliorates the Anxiety- and Depression-Like Behavior of Subclinical Hypothyroidism Rat: Possible Involvement of the HPT Axis, HPA Axis, and Wnt/beta Catenin Pathway. AB - Metabolic disease subclinical hypothyroidism (SCH) is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES) in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 MUg/kg for 16 days. The rats' plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic-pituitary-adrenal (HPA) activity were evaluated. The protein expression levels of the Wnt/beta-catenin in the hippocampus were detected by western blot. The results showed that RES treatment downregulated the elevated plasma thyroid-stimulating hormone concentration and the hypothalamic mRNA expression of thyrotropin-releasing hormone in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the open-field test, increased sucrose preference in the sucrose preference test, and decreased immobility in the forced swimming test compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels, and the hypothalamic corticotrophin-releasing hormone mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment upregulated the relative ratio of phosphorylated-GSK3beta (p-GSK3beta)/GSK3beta and protein levels of p-GSK3beta, cyclin D1, and c-myc, while downregulating the relative ratio of phosphorylated-beta-catenin (p-beta-catenin)/beta-catenin and expression of GSK3beta in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by downregulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt/beta catenin pathway. PMID- 27252680 TI - Silencing the Nucleocytoplasmic O-GlcNAc Transferase Reduces Proliferation, Adhesion, and Migration of Cancer and Fetal Human Colon Cell Lines. AB - The post-translational modification of proteins by O-linked beta-N acetylglucosamine (O-GlcNAc) is regulated by a unique couple of enzymes. O-GlcNAc transferase (OGT) transfers the GlcNAc residue from UDP-GlcNAc, the final product of the hexosamine biosynthetic pathway (HBP), whereas O-GlcNAcase (OGA) removes it. This study and others show that OGT and O-GlcNAcylation levels are increased in cancer cell lines. In that context, we studied the effect of OGT silencing in the colon cancer cell lines HT29 and HCT116 and the primary colon cell line CCD841CoN. Herein, we report that OGT silencing diminished proliferation, in vitro cell survival and adhesion of primary and cancer cell lines. SiOGT dramatically decreased HT29 and CCD841CoN migration, CCD841CoN harboring high capabilities of migration in Boyden chamber system when compared to HT29 and HCT116. The expression levels of actin and tubulin were unaffected by OGT knockdown but siOGT seemed to disorganize microfilament, microtubule, and vinculin networks in CCD841CoN. While cancer cell lines harbor higher levels of OGT and O-GlcNAcylation to fulfill their proliferative and migratory properties, in agreement with their higher consumption of HBP main substrates glucose and glutamine, our data demonstrate that OGT expression is not only necessary for the biological properties of cancer cell lines but also for normal cells. PMID- 27252682 TI - Low Fermentation pH Is a Trigger to Alcohol Production, but a Killer to Chain Elongation. AB - Gasification of organic wastes coupled to syngas fermentation allows the recovery of carbon in the form of commodity chemicals, such as carboxylates and biofuels. Acetogenic bacteria ferment syngas to mainly two-carbon compounds, although a few strains can also synthesize four-, and six-carbon molecules. In general, longer carbon chain products have a higher biotechnological (and commercial) value due to their higher energy content and their lower water solubility. However, de-novo synthesis of medium-chain products from syngas is quite uncommon in acetogenic bacteria. An alternative to de-novo synthesis is bioproduction of short-chain products (C2 and C4), and their subsequent elongation to C4, C6, or C8 through reversed beta-oxidation metabolism. This two-step synergistic approach has been successfully applied for the production of up to C8 compounds, although the accumulation of alcohols in these mixed cultures remained below detection limits. The present work investigates the production of higher alcohols from syngas by open mixed cultures (OMC). A syngas-fermenting community was enriched from sludge of an anaerobic digester for a period of 109 days in a lab-scale reactor. At the end of this period, stable production of ethanol and butanol was obtained. C6 compounds were only transiently produced at the beginning of the enrichment phase, during which Clostridium kluyveri, a bacterium able to carry out carbon chain elongation, was detected in the community. Further experiments showed pH as a critical parameter to maintain chain elongation activity in the co-culture. Production of C6 compounds was recovered by preventing fermentation pH to decrease below pH 4.5-5. Finally, experiments showed maximal production of C6 compounds (0.8 g/L) and alcohols (1.7 g/L of ethanol, 1.1 g/L of butanol, and 0.6 g/L of hexanol) at pH 4.8. In conclusion, low fermentation pH is critical for the production of alcohols, although detrimental to C. kluyveri. Fine control of fermentation pH to final values around 4.8 could allow sustained production of higher alcohols. PMID- 27252681 TI - Francisella philomiragia Infection and Lethality in Mammalian Tissue Culture Cell Models, Galleria mellonella, and BALB/c Mice. AB - Francisella (F.) philomiragia is a Gram-negative bacterium with a preference for brackish environments that has been implicated in causing bacterial infections in near-drowning victims. The purpose of this study was to characterize the ability of F. philomiragia to infect cultured mammalian cells, a commonly used invertebrate model, and, finally, to characterize the ability of F. philomiragia to infect BALB/c mice via the pulmonary (intranasal) route of infection. This study shows that F. philomiragia infects J774A.1 murine macrophage cells, HepG2 cells and A549 human Type II alveolar epithelial cells. However, replication rates vary depending on strain at 24 h. F. philomiragia infection after 24 h was found to be cytotoxic in human U937 macrophage-like cells and J774A.1 cells. This is in contrast to the findings that F. philomiragia was non-cytotoxic to human hepatocellular carcinoma cells, HepG2 cells and A549 cells. Differential cytotoxicity is a point for further study. Here, it was demonstrated that F. philomiragia grown in host-adapted conditions (BHI, pH 6.8) is sensitive to levofloxacin but shows increased resistance to the human cathelicidin LL-37 and murine cathelicidin mCRAMP when compared to related the Francisella species, F. tularensis subsp. novicida and F. tularensis subsp. LVS. Previous findings that LL-37 is strongly upregulated in A549 cells following F. tularensis subsp. novicida infection suggest that the level of antimicrobial peptide expression is not sufficient in cells to eradicate the intracellular bacteria. Finally, this study demonstrates that F. philomiragia is lethal in two in vivo models; Galleria mellonella via hemocoel injection, with a LD50 of 1.8 * 10(3), and BALB/c mice by intranasal infection, with a LD50 of 3.45 * 10(3). In conclusion, F. philomiragia may be a useful model organism to study the genus Francisella, particularly for those researchers with interest in studying microbial ecology or environmental strains of Francisella. Additionally, the Biosafety level 2 status of F. philomiragia makes it an attractive model for virulence and pathogenesis studies. PMID- 27252683 TI - The Geobacillus Pan-Genome: Implications for the Evolution of the Genus. AB - The genus Geobacillus is comprised of a diverse group of spore-forming Gram positive thermophilic bacterial species and is well known for both its ecological diversity and as a source of novel thermostable enzymes. Although the mechanisms underlying the thermophilicity of the organism and the thermostability of its macromolecules are reasonably well understood, relatively little is known of the evolutionary mechanisms, which underlie the structural and functional properties of members of this genus. In this study, we have compared 29 Geobacillus genomes, with a specific focus on the elements, which comprise the conserved core and flexible genomes. Based on comparisons of conserved core and flexible genomes, we present evidence of habitat delineation with specific Geobacillus genomes linked to specific niches. Our analysis revealed that Geobacillus and Anoxybacillus share a high proportion of genes. Moreover, the results strongly suggest that horizontal gene transfer is a major factor deriving the evolution of Geobacillus from Bacillus, with genetic contributions from other phylogenetically distant taxa. PMID- 27252684 TI - Diversity of Pneumocystis jirovecii during Infection Revealed by Ultra-Deep Pyrosequencing. AB - Pneumocystis jirovecii is an uncultivable fungal pathogen responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, the physiopathology of which is only partially understood. The diversity of the Pneumocystis strains associated with acute infection has mainly been studied by Sanger sequencing techniques precluding any identification of rare genetic events (< 20% frequency). We used next-generation sequencing to detect minority variants causing infection, and analyzed the complexity of the genomes of infection causing P. jirovecii. Ultra-deep pyrosequencing (UDPS) of PCR amplicons of two nuclear target region [internal transcribed spacer 2 (ITS2) and dihydrofolate reductase (DHFR)] and one mitochondrial DNA target region [the mitochondrial ribosomal RNA large subunit gene (mtLSU)] was performed on 31 samples from 25 patients. UDPS revealed that almost all patients (n = 23/25, 92%) were infected with mixtures of strains. An analysis of repeated samples from six patients showed that the proportion of each variant change significantly (by up to 30%) over time on treatment in three of these patients. A comparison of mitochondrial and nuclear UDPS data revealed heteroplasmy in P. jirovecii. The recognition site for the homing endonuclease I-SceI was recovered from the mtLSU gene, whereas its two conserved motifs of the enzyme were not. This suggests that heteroplasmy may result from recombination induced by unidentified homing endonucleases. This study sheds new light on the biology of P. jirovecii during infection. PCP results from infection not with a single microorganism, but with a complex mixture of different genotypes, the proportions of which change over time due to intricate selection and reinfection mechanisms that may differ between patients, treatments, and predisposing diseases. PMID- 27252685 TI - Bacterial Endophytes Isolated from Plants in Natural Oil Seep Soils with Chronic Hydrocarbon Contamination. AB - The bacterial endophytic communities of four plants growing abundantly in soils highly contaminated by hydrocarbons were analyzed through culturable and culture independent means. Given their tolerance to the high levels of petroleum contamination at our study site, we sought evidence that Achillea millefolium, Solidago canadensis, Trifolium aureum, and Dactylis glomerata support high levels of hydrocarbon degrading endophytes. A total of 190 isolates were isolated from four plant species. The isolates were identified by partial 16S rDNA sequence analysis, with class Actinobacteria as the dominant group in all species except S. canadensis, which was dominated by Gammaproteobacteria. Microbacterium foliorum and Plantibacter flavus were present in all the plants, with M. foliorum showing predominance in D. glomerata and both endophytic bacterial species dominated T. aureum. More than 50% of the isolates demonstrated degradative capabilities for octanol, toluene, naphthalene, kerosene, or motor oil based on sole carbon source growth screens involving the reduction of tetrazolium dye. P. flavus isolates from all the sampled plants showed growth on all the petroleum hydrocarbons (PHCs) substrates tested. Mineralization of toluene and naphthalene was confirmed using gas-chromatography. 16S based terminal restriction fragment length polymorphism analysis revealed significant differences between the endophytic bacterial communities showing them to be plant host specific at this site. To our knowledge, this is the first account of the degradation potential of bacterial endophytes in these commonly occurring pioneer plants that were not previously known as phytoremediating plants. PMID- 27252686 TI - In Situ Microbial Community Succession on Mild Steel in Estuarine and Marine Environments: Exploring the Role of Iron-Oxidizing Bacteria. AB - Microbiologically influenced corrosion (MIC) is a complex biogeochemical process involving interactions between microbes, metals, minerals, and their environment. We hypothesized that sediment-derived iron-oxidizing bacteria (FeOB) would colonize and become numerically abundant on steel surfaces incubated in coastal marine environments. To test this, steel coupons were incubated on sediments over 40 days, and samples were taken at regular intervals to examine microbial community succession. The experiments were conducted at two locations: (1) a brackish salt marsh stream and (2) a coastal marine bay. We analyzed DNA extracted from the MIC biofilms for bacterial diversity using high-throughput amplicon sequencing of the SSU rRNA gene, and two coupons from the coastal site were single cell sorted and screened for the SSU rRNA gene. We quantified communities of Zetaproteobacteria, sulfate-reducing bacteria (SRB), and total bacteria and archaea using qPCR analyses. Zetaproteobacteria and SRB were identified in the sequencing data and qPCR analyses for samples collected throughout the incubations and were also present in adjacent sediments. At the brackish site, the diversity of Zetaproteobacteria was lower on the steel compared to sediments, consistent with the expected enrichment of FeOB on steel. Their numbers increased rapidly over the first 10 days. At the marine site, Zetaproteobacteria and other known FeOB were not detected in sediments; however, the numbers of Zetaproteobacteria increased dramatically within 10 days on the steel surface, although their diversity was nearly clonal. Iron oxyhydroxide stalk biosignatures were observed on the steel and in earlier enrichment culture studies; this is evidence that the Zetaproteobacteria identified in the qPCR, pyrosequencing, and single cell data were likely FeOB. In the brackish environment, members of freshwater FeOB were also present, but were absent in the fully marine site. This work indicates there is a successional pattern in the colonization of steel surfaces with FeOB being early colonizers; over time the MIC community matures to include other members that may help accelerate corrosion. This work also shows there is a reservoir for Zetaproteobacteria in coastal sediment habitats, where they may influence the coastal iron cycle, and can rapidly colonize steel surfaces or other sources of Fe(II) when available. PMID- 27252687 TI - Comparative Bioinformatics and Experimental Analysis of the Intergenic Regulatory Regions of Bacillus cereus hbl and nhe Enterotoxin Operons and the Impact of CodY on Virulence Heterogeneity. AB - Bacillus cereus is a food contaminant with greatly varying enteropathogenic potential. Almost all known strains harbor the genes for at least one of the three enterotoxins Nhe, Hbl, and CytK. While some strains show no cytotoxicity, others have caused outbreaks, in rare cases even with lethal outcome. The reason for these differences in cytotoxicity is unknown. To gain insight into the origin of enterotoxin expression heterogeneity in different strains, the architecture and role of 5' intergenic regions (5' IGRs) upstream of the nhe and hbl operons was investigated. In silico comparison of 142 strains of all seven phylogenetic groups of B. cereus sensu lato proved the presence of long 5' IGRs upstream of the nheABC and hblCDAB operons, which harbor recognition sites for several transcriptional regulators, including the virulence regulator PlcR, redox regulators ResD and Fnr, the nutrient-sensitive regulator CodY as well as the master regulator for biofilm formation SinR. By determining transcription start sites, unusually long 5' untranslated regions (5' UTRs) upstream of the nhe and hbl start codons were identified, which are not present upstream of cytK-1 and cytK-2. Promoter fusions lacking various parts of the nhe and hbl 5' UTR in B. cereus INRA C3 showed that the entire 331 bp 5' UTR of nhe is necessary for full promoter activity, while the presence of the complete 606 bp hbl 5' UTR lowers promoter activity. Repression was caused by a 268 bp sequence directly upstream of the hbl transcription start. Luciferase activity of reporter strains containing nhe and hbl 5' IGR lux fusions provided evidence that toxin gene transcription is upregulated by the depletion of free amino acids. Electrophoretic mobility shift assays showed that the branched-chain amino acid sensing regulator CodY binds to both nhe and hbl 5' UTR downstream of the promoter, potentially acting as a nutrient-responsive roadblock repressor of toxin gene transcription. PlcR binding sites are highly conserved among all B. cereus sensu lato strains, indicating that this regulator does not significantly contribute to the heterogeneity in virulence potentials. The CodY recognition sites are far less conserved, perhaps conferring varying strengths of CodY binding, which might modulate toxin synthesis in a strain-specific manner. PMID- 27252688 TI - A Game of Russian Roulette for a Generalist Dinoflagellate Parasitoid: Host Susceptibility Is the Key to Success. AB - Marine microbial interactions involving eukaryotes and their parasites play an important role in shaping the structure of phytoplankton communities. These interactions may alter population densities of the main host, which in turn may have consequences for the other concurrent species. The effect generalist parasitoids exert on a community is strongly dependent on the degree of host specificity. Parvilucifera sinerae is a generalist parasitoid able to infect a wide range of dinoflagellates, including toxic-bloom-forming species. A density dependent chemical cue has been identified as the trigger for the activation of the infective stage. Together these traits make Parvilucifera-dinoflagellate hosts a good model to investigate the degree of specificity of a generalist parasitoid, and the potential effects that it could have at the community level. Here, we present for the first time, the strategy by which a generalist dinoflagellate parasitoid seeks out its host and determine whether it exhibits host preferences, highlighting key factors in determining infection. Our results demonstrate that in its infective stage, P. sinerae is able to sense potential hosts, but does not actively select among them. Instead, the parasitoids contact the host at random, governed by the encounter probability rate and once encountered, the chance to penetrate inside the host cell and develop the infection strongly depends on the degree of host susceptibility. As such, their strategy for persistence is more of a game of Russian roulette, where the chance of survival is dependent on the susceptibility of the host. Our study identifies P. sinerae as a potential key player in community ecology, where in mixed dinoflagellate communities consisting of hosts that are highly susceptible to infection, parasitoid preferences may mediate coexistence between host species, reducing the dominance of the superior competitor. Alternatively, it may increase competition, leading to species exclusion. If, however, highly susceptible hosts are absent from the community, the parasitoid population could suffer a dilution effect maintaining a lower parasitoid density. Therefore, both host community structure and host susceptibility will determine infectivity in the field. PMID- 27252689 TI - Molecular Evidence for Metabolically Active Bacteria in the Atmosphere. AB - Bacterial metabolisms are responsible for critical chemical transformations in nearly all environments, including oceans, freshwater, and soil. Despite the ubiquity of bacteria in the atmosphere, little is known about the metabolic functioning of atmospheric bacterial communities. To gain a better understanding of the metabolism of bacterial communities in the atmosphere, we used a combined empirical and model-based approach to investigate the structure and composition of potentially active bacterial communities in air sampled at a high elevation research station. We found that the composition of the putatively active bacterial community (assayed via rRNA) differed significantly from the total bacterial community (assayed via rDNA). Rare taxa in the total (rDNA) community were disproportionately active relative to abundant taxa, and members of the order Rhodospirillales had the highest potential for activity. We developed theory to explore the effects of random sampling from the rRNA and rDNA communities on observed differences between the communities. We found that random sampling, particularly in cases where active taxa are rare in the rDNA community, will give rise to observed differences in community composition including the occurrence of "phantom taxa", taxa which are detected in the rRNA community but not the rDNA community. We show that the use of comparative rRNA/rDNA techniques can reveal the structure and composition of the metabolically active portion of bacterial communities. Our observations suggest that metabolically active bacteria exist in the atmosphere and that these communities may be involved in the cycling of organic compounds in the atmosphere. PMID- 27252690 TI - Evaluation of Strategies to Separate Root-Associated Microbial Communities: A Crucial Choice in Rhizobiome Research. AB - Plants shape distinct, species-specific microbiomes in their rhizospheres. A main premise for evaluating microbial communities associated with root-soil compartments is their successful separation into the rhizosphere (soil-root interface), the rhizoplane (root surface), and the endosphere (inside roots). We evaluated different approaches (washing, sonication, and bleaching) regarding their efficiency to separate microbial cells associated with different root compartments of soil-grown rice using fluorescence microscopy and community fingerprinting of 16S rRNA genes. Vigorous washing detached 45% of the rhizoplane population compared to untreated roots. Additional sonication reduced rhizoplane attached microorganisms by up to 78% but caused various degrees of root tissue destruction at all sonication intensities tested. Treatment with sodium hypochlorite almost completely (98%) removed rhizoplane-associated microbial cells. Community fingerprinting revealed that microbial communities obtained from untreated, washed, and sonicated roots were not statistically distinguishable. Hypochlorite-treated roots harbored communities significantly different from all other samples, likely representing true endospheric populations. Applying these procedures to other root samples (bean and clover) revealed that treatment efficiencies were strongly affected by root morphological parameters such as root hair density and rigidity of epidermis. Our findings suggest that a careful evaluation of separation strategies prior to molecular community analysis is indispensable, especially when endophytes are the subject of interest. PMID- 27252691 TI - Ecotoxicological Impact of the Bioherbicide Leptospermone on the Microbial Community of Two Arable Soils. AB - The ecotoxicological impact of leptospermone, a beta-triketone bioherbicide, on the bacterial community of two arable soils was investigated. Soil microcosms were exposed to 0 * (control), 1 * or 10 * recommended dose of leptospermone. The beta-triketone was moderately adsorbed to both soils (i.e.,: K fa ~ 1.2 and K oc ~ 140 mL g(-1)). Its dissipation was lower in sterilized than in unsterilized soils suggesting that it was mainly influenced by biotic factors. Within 45 days, leptospermone disappeared almost entirely from one of the two soils (i.e., DT50 < 10 days), while 25% remained in the other. The composition of the microbial community assessed by qPCR targeting 11 microbial groups was found to be significantly modified in soil microcosms exposed to leptospermone. Pyrosequencing of 16S rRNA gene amplicons showed a shift in the bacterial community structure and a significant impact of leptospermone on the diversity of the soil bacterial community. Changes in the composition, and in the alpha- and beta-diversity of microbial community were transient in the soil able to fully dissipate the leptospermone, but were persistent in the soil where beta-triketone remained. To conclude the bacterial community of the two soils was sensitive to leptospermone and its resilience was observed only when leptospermone was fully dissipated. PMID- 27252692 TI - Systemic Concentrations of Short Chain Fatty Acids Are Elevated in Salmonellosis and Exacerbation of Familial Mediterranean Fever. AB - Gut microbiota-produced short chain fatty acids (SCFAs) play an important role in the normal human metabolism and physiology. Although the gradients of SCFAs from the large intestine, where they are largely produced, to the peripheral blood as well as the main routes of SCFA metabolism by different organs are known well for the healthy state, there is a paucity of information regarding how these are affected in disease. In particular, how the inflammation caused by infection or autoinflammatory disease affect the concentration of SCFAs in the peripheral venous blood. In this work, we revealed that diseases caused either by infectious agents (two Salmonella enterica serovars, S. Enteritidis, and S. Typhimurium) or by the exacerbation of an autoinflammatory disease, familial Mediterranean fever (FMF), both result in a significantly elevated systemic concentration of SCFAs. In the case of salmonellosis the concentration of SCFAs in peripheral blood was significantly and consistently higher, from 5- to 20-fold, compared to control. In the case of FMF, however, a significant increase of SCFAs in the peripheral venous blood was detected only in the acute phase of the disease, with a lesser impact in remission. It seems counterintuitive that the dysbiotic conditions, with a reduced number of gut microorganisms, produce such an effect. This phenomenon, however, must be appraised within the context of how the inflammatory diseases affect the normal physiology. We discuss a number of factors that may contribute to the "leak" and persistence of gut-produced SCFAs into the systemic circulation in infectious and autoinflammatory diseases. PMID- 27252693 TI - Metagenomic Reconstruction of Key Anaerobic Digestion Pathways in Municipal Sludge and Industrial Wastewater Biogas-Producing Systems. AB - Anaerobic digestion (AD) is a microbial process widely used to treat organic wastes. While the microbes involved in digestion of municipal sludge are increasingly well characterized, the taxonomic and functional compositions of AD digesters treating industrial wastewater have been understudied. This study examined metagenomes from a biogas-producing digester treating municipal sludge in Shek Wu Hui (SWH), Hong Kong and an industrial wastewater digester in Guangzhou (GZ), China, and compared their taxonomic composition and reconstructed biochemical pathways. Genes encoding carbohydrate metabolism and protein metabolism functions were overrepresented in GZ, while genes encoding functions related to fatty acids, lipids and isoprenoids were overrepresented in SWH, reflecting the plants' feedstocks. Mapping of genera to functions in each community indicated that both digesters had a high level of functional redundancy, and a more even distribution of genera in GZ suggested that it was more functionally stable. While fermentation in both samples was dominated by Clostridia, SWH had an overrepresentation of Proteobacteria, including syntrophic acetogens, reflecting its more complex substrate. Considering the growing importance of biogas as an alternative fuel source, a detailed mechanistic understanding of AD is important and this report will be a basis for further study of industrial wastewater AD. PMID- 27252694 TI - Recent Reticulate Evolution in the Ecologically Dominant Lineage of Coccolithophores. AB - The coccolithophore family Noelaerhabdaceae contains a number of taxa that are very abundant in modern oceans, including the cosmopolitan bloom-forming Emiliania huxleyi. Introgressive hybridization has been suggested to account for incongruences between nuclear, mitochondrial and plastidial phylogenies of morphospecies within this lineage, but the number of species cultured to date remains rather limited. Here, we present the characterization of 5 new Noelaerhabdaceae culture strains isolated from samples collected in the south east Pacific Ocean. These were analyzed morphologically using scanning electron microscopy and phylogenetically by sequencing 5 marker genes (nuclear 18S and 28S rDNA, plastidial tufA, and mitochondrial cox1 and cox3 genes). Morphologically, one of these strains corresponded to Gephyrocapsa ericsonii and the four others to Reticulofenestra parvula. Ribosomal gene sequences were near identical between these new strains, but divergent from G. oceanica, G. muellerae, and E. huxleyi. In contrast to the clear distinction in ribosomal phylogenies, sequences from other genomic compartments clustered with those of E. huxleyi strains with which they share an ecological range (i.e., warm temperate to tropical waters). These data provide strong support for the hypothesis of past (and potentially ongoing) introgressive hybridization within this ecologically important lineage and for the transfer of R. parvula to Gephyrocapsa. These results have important implications for understanding the role of hybridization in speciation in vast ocean meta-populations of phytoplankton. PMID- 27252695 TI - Innate Immune Responses in ALV-J Infected Chicks and Chickens with Hemangioma In Vivo. AB - Avian leukosis virus subgroup J (ALV-J) infection can cause tumors and immunosuppression. Since the precise mechanism of the innate immune response induced by ALV-J is unknown, we investigated the antiviral innate immune responses induced by ALV-J in chicks and chickens that had developed tumors. Spleen levels of interleukin-6 (IL-6), IL-10, IL-1beta, and interferon-beta (IFN beta) were not significantly different between the infected chick groups and the control groups from 1 day post hatch to 7 days post hatch. However, IL-6, IL 1beta, and IFN-beta protein levels in the three clinical samples with hemangiomas were dramatically increased compared to the healthy samples. In addition, the anti-inflammatory cytokine IL-10 increased sharply in two of three clinical samples. We also found a more than 20-fold up-regulation of ISG12-1 mRNA at 1 day post infection (d.p.i.) and a twofold up-regulation of ZC3HAV1 mRNA at 4 d.p.i. However, there were no statistical differences in ISG12-1 and ZC3HAV1 mRNA expression levels in the tumorigenesis phase. ALV-J infection induced a significant increase of Toll-like receptor 7 (TLR-7) at 1 d.p.i. and dramatically increased the mRNA levels of melanoma differentiation-associated gene 5 (MDA5) in the tumorigenesis phase. Moreover, the protein levels of interferon regulatory factor 1 (IRF-1) and signal transducer and activator of transcription 1 (STAT1) were decreased in chickens with tumors. These results suggest that ALV-J was primarily recognized by chicken TLR7 and MDA5 at early and late in vivo infection stages, respectively. ALV-J strain SCAU-HN06 did not induce any significant antiviral innate immune response in 1 week old chicks. However, interferon stimulated genes were not induced normally during the late phase of ALV-J infection due to a reduction of IRF1 and STAT1 expression. PMID- 27252696 TI - Bacterial and Fungal Microbiota Changes Distinguish C. difficile Infection from Other Forms of Diarrhea: Results of a Prospective Inpatient Study. AB - This study sought to characterize the bacterial and fungal microbiota changes associated with Clostridium difficile infection (CDI) among inpatients with diarrhea, in order to further explain the pathogenesis of this infection as well as to potentially guide new CDI therapies. Twenty-four inpatients with diarrhea were enrolled, 12 of whom had CDI. Each patient underwent stool testing for CDI prior to being treated with difficile-directed antibiotics, when appropriate. Clinical data was obtained from the medical record, while each stool sample underwent 16S rRNA and ITS sequencing for bacterial and fungal elements. An analysis of microbial community structures distinct to the CDI population was also performed. The results demonstrated no difference between the CDI and non CDI cohorts with respect to any previously reported CDI risk factors. Butyrogenic bacteria were enriched in both CDI and non-CDI patients. A previously unreported finding of increased numbers of Akkermansia muciniphila in CDI patients was observed, an organism which degrades mucin and which therefore may provide a selective advantage toward CDI. Fungal elements of the genus Penicillium were predominant in CDI; these organisms produce antibacterial chemicals which may resist recovery of healthy microbiota. The most frequent CDI microbial community networks involved Peptostreptococcaceae and Enterococcus, with decreased population density of Bacteroides. These results suggest that the development of CDI is associated with microbiota changes which are consistently associated with CDI in human subjects. These gut taxa contribute to the intestinal dysbiosis associated with C. difficile infection. PMID- 27252697 TI - Biochemical Characterization of 3-Methyl-4-nitrophenol Degradation in Burkholderia sp. Strain SJ98. AB - Several strains have been reported to grow on 3-methyl-4-nitrophenol (3M4NP), the primary breakdown product of the excessively used insecticide fenitrothion. However, the microbial degradation of 3M4NP at molecular and biochemical levels remains unknown. Here, methyl-1,4-benzoquinone (MBQ) and methylhydroquinone (MHQ), rather than catechol proposed previously, were identified as the intermediates before ring cleavage during 3M4NP degradation by Burkholderia sp. strain SJ98. Real-time quantitative PCR analysis indicated that the pnpABA1CDEF cluster involved in para-nitrophenol (PNP) and 2-chloro-4-nitrophenol (2C4NP) catabolism was also likely responsible for 3M4NP degradation in this strain. Purified PNP 4-monooxygenase (PnpA) is able to catalyze the monooxygenation of 3M4NP to MBQ and exhibited an apparent K m value of 20.3 +/- 2.54 MUM for 3M4NP, and pnpA is absolutely necessary for the catabolism of 3M4NP by gene knock-out and complementation. PnpB, a 1,4-benzoquinone reductase catalyzes the reduction of MBQ to MHQ, and also found to enhance PnpA activity in vitro in the conversion of 3M4NP to MBQ. By sequential catalysis assays, PnpCD, PnpE, and PnpF were likely involved in the lower pathway of 3M4NP catabolism. Although NpcCD, NpcE, and NpcF are able to catalyze the sequential conversion of MHQ in vitro, these enzymes are unlikely involved in 3M4NP catabolism because their coding genes were not upregulated by 3M4NP induction in vivo. These results revealed that the enzymes involved in PNP and 2C4NP catabolism were also responsible for 3M4NP degradation in strain SJ98. This fills a gap in our understanding of the microbial degradation of 3M4NP at molecular and biochemical levels and also provides another example to illustrate the adaptive flexibility in microbial catabolism for structurally similar compounds. PMID- 27252698 TI - The Effect of Helicobacter pylori Infection, Aging, and Consumption of Proton Pump Inhibitor on Fungal Colonization in the Stomach of Dyspeptic Patients. AB - BACKGROUND: The importance of coinfection of Helicobacter pylori (H.pylori) and Candida albicans (C. albicans) in the development of gastric diseases is not known. In this study, the frequency of concurrent infection of H. pylori and C. albicans in dyspeptic patients was assessed while considering age, gender, and PPI consumption of patients. METHODS: Gastric biopsies were taken from 74 yeast positive dyspeptic patients and gastric disease, age, gender, and proton pump inhibitor (PPI) consumption of subjects were recorded. One antral biopsy was used for rapid urease test (RUT) and one for H. pylori and yeast cultivation and smear preparation. Bacterial isolates were identified according to spiral morphology and the biochemical characteristics. Yeast isolates were identified on Chromagar and by the Nested-PCR amplification of C. albicans-specific topoisomerase II gene. Twenty-seven biopsy smears were Gram-stained and examined by the light microscope for observing H. pylori and yeast cells. RESULTS: Fifty-four (73%) of patients were >40 year. Of 68 patients with PPI consumption record, 46 (67.6%) consumed PPI (p = 0). Comparison of patients in peptic ulcer group (12, 16.2%) with (6, 8.1%) or without (6, 8.1%) H. pylori or in gastritis group (62, 83.8%) with (25, 33.8%) or without (37, 50%) H. pylori showed no significant difference (p > 0.05). Of the 46 patients who consumed PPI, 13 (17.5%) were H. pylori positive and 33 (44.6%) H. pylori-negative (p = 0). Ten out of twenty-seven smears showed the occurrence of H. pylori cells, including three with yeast cells. Of the 17 H. pylori-negative smears, three showed the occurrence of yeast cells only. Yeasts stained Gram-positive or Gram-negative and appeared as single or budding cells. CONCLUSION: The older age and PPI consumption could favor fungal colonization in the human stomach. The occurrence of a considerable number of H. pylori-positive or H. pylori-negative patients with gastritis or peptic ulcer shows that co-infection of Candida and H. pylori or infection of yeast alone could be associated with dyspeptic diseases. The occurrence of yeast cells in gastric biopsies with different Gram's reactions indicates that fungi might change their cell wall components for establishing a persistent colonization in the stomach. PMID- 27252699 TI - Second Messenger Signaling in Bacillus subtilis: Accumulation of Cyclic di-AMP Inhibits Biofilm Formation. AB - The Gram-positive model organism Bacillus subtilis produces the essential second messenger signaling nucleotide cyclic di-AMP. In B. subtilis and other bacteria, c-di-AMP has been implicated in diverse functions such as control of metabolism, cell division and cell wall synthesis, and potassium transport. To enhance our understanding of the multiple functions of this second messenger, we have studied the consequences of c-di-AMP accumulation at a global level by a transcriptome analysis. C-di-AMP accumulation affected the expression of about 700 genes, among them the two major operons required for biofilm formation. The expression of both operons was severely reduced both in the laboratory and a non-domesticated strain upon accumulation of c-di-AMP. In excellent agreement, the corresponding strain was unable to form complex colonies. In B. subtilis, the transcription factor SinR controls the expression of biofilm genes by binding to their promoter regions resulting in transcription repression. Inactivation of the sinR gene restored biofilm formation even at high intracellular c-di-AMP concentrations suggesting that the second messenger acts upstream of SinR in the signal transduction pathway. As c-di-AMP accumulation did not affect the intracellular levels of SinR, we conclude that the nucleotide affects the activity of SinR. PMID- 27252700 TI - Toll-Like Receptor 2 Mediates In Vivo Pro- and Anti-inflammatory Effects of Mycobacterium Tuberculosis and Modulates Autoimmune Encephalomyelitis. AB - Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll-like receptor 2 (Tlr2), by exploiting a previously characterized Tlr2 variant (Met82Ile). Tlr2 82ile promoted self-specific proinflammatory polarization as well as expansion of ag-specific FoxP3(+) Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-gamma and IL-17 proinflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participated directly to a putative binding pocket for sugars and cadherins. The distinct pro- and anti-inflammatory actions impacted severity, extent of remission, and distribution of the lesions within the central nervous system of experimental autoimmune encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses. PMID- 27252701 TI - CD1c-Related DCs that Express CD207/Langerin, but Are Distinguishable from Langerhans Cells, Are Consistently Present in Human Tonsils. AB - Several subsets of dendritic cells (DCs) are present in the oropharyngeal tonsillar tissues and are thought to behave as major actors in development and regulation of immunity by acting as a first line of recognition for airborne and alimentary antigens. We previously discovered in human adult tonsils infected with Epstein-Barr virus (EBV), a subset of DCs that expressed langerin/CD207, a lectin usually recognized as a hallmark of epidermal Langerhans cells (LCs). In the present study, we analyzed the content of several child and adult tonsils in order to characterize in more detail the phenotype of these tonsillar CD207 expressing DCs (tCD207 DCs) and to compare it with that of other human DC subsets. We showed that all the human tonsils studied (n = 12) contained significant proportions of tCD207 DCs among tonsillar cells expressing HLA-DR. Moreover, the presence of tCD207 DCs in tonsils from young children free of EBV infection indicated that these cells could be established early in the tonsil independently of EBV infection. We also showed that tCD207 DCs, that were found mainly located within the tonsillar lymphoid stroma, were distinguishable from LCs by the level of expression of CD1a and EpCAM, and also from human inflammatory DCs by the lack of CD1a, CD206, and CD14 expression. Detailed analysis of cell surface DC markers showed that tCD207 DCs were unrelated to CD141(+) DCs or macrophages, but defined a subtype of tonsillar DCs closely related to myeloid resident CD1c DCs. Since it was established that blood CD1c myeloid DCs exhibit plasticity and are capable of expressing CD207 notably in the presence of inflammatory cytokines, it is tempting to speculate that CD207(+) CD1c(+) DCs may play a specific immune role. PMID- 27252702 TI - Accessory Factors of Cytoplasmic Viral RNA Sensors Required for Antiviral Innate Immune Response. AB - Type I interferon (IFN) induces many antiviral factors in host cells. RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs) and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1alpha/gamma dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and, thus, cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway. PMID- 27252704 TI - Relevance of HLA-DP/DQ and ICAM-1 SNPs among Ovarian Cancer Patients. AB - BACKGROUND: Ovarian cancer is one of the most lethal gynecological malignancies and the fifth leading cause of cancer deaths among women. The high mortality rate is largely attributed to its diagnosis in advanced stages. Poor prognosis of ovarian cancer is usually due to the lack of specific or effective screening and diagnostic methods for identifying early-stage disease. AIM: Our study aimed to study the role of HLA-DP, HLA-DQ, and ICAM-1 SNPs in diagnosis and/or prognosis of ovarian tumors. SUBJECTS AND METHODS: The current study was conducted on 60 patients with ovarian tumors (benign, borderline, and malignant) and 20 healthy volunteers. Genotyping of HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs was done using 5' nuclease assay. RESULTS: We found significant association of HLA-DP rs3077 AA, HLA-DQ rs3920 GG, ICAM-1 rs1437 CC, and CT genotypes with increased risk of ovarian cancer (OR = 43.5, 6, 25, and 2.6, respectively). In addition, HLA-DQ rs3920 and ICAM-1 rs1437 alleles vary significantly among different types of ovarian cancer (P = 0.003 and 0.001, respectively). CONCLUSION: HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs could help in the diagnosis and prognosis of ovarian cancer. PMID- 27252703 TI - Spatiotemporal Regulation of Hsp90-Ligand Complex Leads to Immune Activation. AB - Although heat shock proteins (HSPs) primarily play a pivotal role in the maintenance of cellular homeostasis while reducing extracellular as well as intracellular stresses, their role in immunologically relevant scenarios, including activation of innate immunity as danger signals, antitumor immunity, and autoimmune diseases, is now gaining much attention. The most prominent feature of HSPs is that they function both in their own and as an HSP-ligand complex. We here show as a unique feature of extracellular HSPs that they target chaperoned molecules into a particular endosomal compartment of dendritic cells, thereby inducing innate and adaptive immune responses via spatiotemporal regulation. PMID- 27252706 TI - Commentary: Acute Hemorrhagic Leukoencephalitis (Weston-Hurst Syndrome) in a Patient with Relapse-Remitting Multiple Sclerosis. PMID- 27252705 TI - A Subset of Patients with Acute Myeloid Leukemia Has Leukemia Cells Characterized by Chemokine Responsiveness and Altered Expression of Transcriptional as well as Angiogenic Regulators. AB - Acute myeloid leukemia (AML) is an aggressive and heterogeneous bone marrow malignancy, the only curative treatment being intensive chemotherapy eventually in combination with allogeneic stem cell transplantation. Both the AML and their neighboring stromal cells show constitutive chemokine release, but chemokines seem to function as regulators of AML cell proliferation only for a subset of patients. Chemokine targeting is therefore considered not only for immunosuppression in allotransplanted patients but also as a possible antileukemic strategy in combination with intensive chemotherapy or as part of disease-stabilizing treatment at least for the subset of patients with chemokine responsive AML cells. In this study, we characterized more in detail the leukemia cell phenotype of the chemokine-responsive patients. We investigated primary AML cells derived from 79 unselected patients. Standardized in vitro suspension cultures were used to investigate AML cell proliferation, and global gene expression profiles were compared for chemokine responders and non-responders identified through the proliferation assays. CCL28-induced growth modulation was used as marker of chemokine responsiveness, and 38 patients were then classified as chemokine-responsive. The effects of exogenous CCL28 (growth inhibition/enhancement/no effect) thus differed among patients and was also dependent on the presence of exogenous hematopoietic growth factors as well as constitutive AML cell cytokine release. The effect of CCR1 inhibition in the presence of chemokine-secreting mesenchymal stem cells also differed among patients. Chemokine-responsive AML cells showed altered expression of genes important for (i) epigenetic transcriptional regulation, particularly lysine acetylation; (ii) helicase activity, especially DExD/H RNA helicases; and (iii) angioregulatory proteins important for integrin binding. Thus, chemokine responsiveness is part of a complex AML cell phenotype with regard to extracellular communication and transcriptional regulation. Chemokine targeting in chemokine-responsive patients may thereby alter AML cell trafficking and increase their susceptibility toward antileukemic treatment, e.g., conventional chemotherapy or targeting of other phenotypic characteristics of the chemokine responsive cells. PMID- 27252707 TI - Spatial Self-Organization of Vegetation Subject to Climatic Stress-Insights from a System Dynamics-Individual-Based Hybrid Model. AB - In simulation models of populations or communities, individual plants have often been obfuscated in favor of aggregated vegetation. This simplification comes with a loss of biological detail and a smoothing out of the demographic noise engendered by stochastic individual-scale processes and heterogeneities, which is significant among others when studying the viability of small populations facing challenging fluctuating environmental conditions. This consideration has motivated the development of precise plant-centered models. The accuracy gained in the representation of plant biology has then, however, often been balanced by the disappearance in models of important plant-soil interactions (esp. water dynamics) due to the inability of most individual-based frameworks to simulate complex continuous processes. In this study, we used a hybrid modeling approach, namely integrated System Dynamics (SD)-Individual-based (IB), to illustrate the importance of individual plant dynamics to explain spatial self-organization of vegetation in arid environments. We analyzed the behavior of this model under different parameter sets either related to individual plant properties (such as seed dispersal distance and reproductive age) or the environment (such as intensity and yearly distribution of precipitation events). While the results of this work confirmed the prevailing theory on vegetation patterning, they also revealed the importance therein of plant-level processes that cannot be rendered by reaction-diffusion models. Initial spatial distribution of plants, reproductive age, and average seed dispersal distance, by impacting patch size and vegetation aggregation, affected pattern formation and population survival under climatic variations. Besides, changes in precipitation regime altered the demographic structure and spatial organization of vegetation patches by affecting plants differentially depending on their age and biomass. Water availability influenced non-linearly total biomass density. Remarkably, lower precipitation resulted in lower mean plant age yet higher mean individual biomass. Moreover, seasonal variations in rainfall greater than a threshold (here, +/-0.45 mm from the 1.3 mm baseline) decreased mean total biomass and generated limit cycles, which, in the case of large variations, were preceded by chaotic demographic and spatial behavior. In some cases, peculiar spatial patterns (e.g., rings) were also engendered. On a technical note, the shortcomings of the present model and the benefit of hybrid modeling for virtual investigations in plant science are discussed. PMID- 27252708 TI - GintAMT3 - a Low-Affinity Ammonium Transporter of the Arbuscular Mycorrhizal Rhizophagus irregularis. AB - Nutrient acquisition and transfer are essential steps in the arbuscular mycorrhizal (AM) symbiosis, which is formed by the majority of land plants. Mineral nutrients are taken up by AM fungi from the soil and transferred to the plant partner. Within the cortical plant root cells the fungal hyphae form tree like structures (arbuscules) where the nutrients are released to the plant-fungal interface, i.e., to the periarbuscular space, before being taken up by the plant. In exchange, the AM fungi receive carbohydrates from the plant host. Besides the well-studied uptake of phosphorus (P), the uptake and transfer of nitrogen (N) plays a crucial role in this mutualistic interaction. In the AM fungus Rhizophagus irregularis (formerly called Glomus intraradices), two ammonium transporters (AMT) were previously described, namely GintAMT1 and GintAMT2. Here, we report the identification and characterization of a newly identified R. irregularis AMT, GintAMT3. Phylogenetic analyses revealed high sequence similarity to previously identified AM fungal AMTs and a clear separation from other fungal AMTs. Topological analysis indicated GintAMT3 to be a membrane bound pore forming protein, and GFP tagging showed it to be highly expressed in the intraradical mycelium of a fully established AM symbiosis. Expression of GintAMT3 in yeast successfully complemented the yeast AMT triple deletion mutant (MATa ura3 mep1Delta mep2Delta::LEU2 mep3Delta::KanMX2). GintAMT3 is characterized as a low affinity transport system with an apparent Km of 1.8 mM and a V max of 240 nmol(-1) min(-1) 10(8) cells(-1), which is regulated by substrate concentration and carbon supply. PMID- 27252709 TI - Transcriptomic Analysis Identifies Differentially Expressed Genes (DEGs) Associated with Bolting and Flowering in Radish (Raphanus sativus L.). AB - The transition of vegetative growth to bolting and flowering is an important process in the life cycle of plants, which is determined by numerous genes forming an intricate network of bolting and flowering. However, no comprehensive identification and profiling of bolting and flowering-related genes have been carried out in radish. In this study, RNA-Seq technology was applied to analyze the differential gene expressions during the transition from vegetative stage to reproductive stage in radish. A total of 5922 differentially expressed genes (DEGs) including 779 up-regulated and 5143 down-regulated genes were isolated. Functional enrichment analysis suggested that some DEGs were involved in hormone signaling pathways and the transcriptional regulation of bolting and flowering. KEGG-based analysis identified 37 DEGs being involved in phytohormone signaling pathways. Moreover, 95 DEGs related to bolting and flowering were identified and integrated into various flowering pathways. Several critical genes including FT, CO, SOC1, FLC, and LFY were characterized and profiled by RT-qPCR analysis. Correlation analysis indicated that 24 miRNA-DEG pairs were involved in radish bolting and flowering. Finally, a miRNA-DEG-based schematic model of bolting and flowering regulatory network was proposed in radish. These outcomes provided significant insights into genetic control of radish bolting and flowering, and would facilitate unraveling molecular regulatory mechanism underlying bolting and flowering in root vegetable crops. PMID- 27252710 TI - The Emerging Role of Protein Phosphorylation as a Critical Regulatory Mechanism Controlling Cellulose Biosynthesis. AB - Plant cell walls are extracellular matrices that surround plant cells and critically influence basic cellular processes, such as cell division and expansion. Cellulose is a major constituent of plant cell walls, and this paracrystalline polysaccharide is synthesized at the plasma membrane by a large protein complex known as the cellulose synthase complex (CSC). Recent efforts have identified numerous protein components of the CSC, but relatively little is known about regulation of cellulose biosynthesis. Numerous phosphoproteomic surveys have identified phosphorylation events in CSC associated proteins, suggesting that protein phosphorylation may represent an important regulatory control of CSC activity. In this review, we discuss the composition and dynamics of the CSC in vivo, the catalog of CSC phosphorylation sites that have been identified, the function of experimentally examined phosphorylation events, and potential kinases responsible for these phosphorylation events. Additionally, we discuss future directions in cellulose synthase kinase identification and functional analyses of CSC phosphorylation sites. PMID- 27252711 TI - Oxidative Metabolism of Rye (Secale cereale L.) after Short Term Exposure to Aluminum: Uncovering the Glutathione-Ascorbate Redox Network. AB - One of the major limitations to plant growth and yield in acidic soils is the prevalence of soluble aluminum ions (Al(3+)) in the soil solution, which can irreversible damage the root apex cells. Nonetheless, many Al-tolerant species overcome Al toxicity and are well-adapted to acidic soils, being able to complete their life cycle under such stressful conditions. At this point, the complex physiological and biochemical processes inherent to Al tolerance remain unclear, especially in what concerns the behavior of antioxidant enzymes and stress indicators at early plant development. Since rye (Secale cereale L.), is considered the most Al-tolerant cereal, in this study we resort to seedlings of two genotypes with different Al sensitivities in order to evaluate their oxidative metabolism after short term Al exposure. Al-induced toxicity and antioxidant responses were dependent on rye genotype, organ and exposure period. Al affected biomass production and membrane integrity in roots and leaves of the sensitive (RioDeva) genotype. Catalase was the primary enzyme involved in H2O2 detoxification in the tolerant (Beira) genotype, while in RioDeva this task was mainly performed by GPX and POX. Evaluation of the enzymatic and non-enzymatic components of the ascorbate-glutathione cycle, as well the oxalate content, revealed that Beira genotype coped with Al stress by converting DHA into oxalate and tartarate, which posteriorly may bind to Al forming non-toxic chelates. In contrast, RioDeva genotype used a much more ineffective strategy which passed through ascorbate regeneration. So, remarkable differences between MDHAR and DHAR activities appear to be the key for a higher Al tolerance. PMID- 27252712 TI - Global Transcriptional Analysis Reveals Unique and Shared Responses in Arabidopsis thaliana Exposed to Combined Drought and Pathogen Stress. AB - With frequent fluctuations in global climate, plants are exposed to co-occurring drought and pathogen infection and this combination adversely affects plant survival. In the past, some studies indicated that morpho-physiological responses of plants to the combined stress are different from the individual stressed plants. However, interaction of drought stressed plants with pathogen has not been widely studied at molecular level. Such studies are important to understand the defense pathways that operate as part of combined stress tolerance mechanism. In this study, Arabidopsis thaliana was exposed to individual drought stress, Pseudomonas syringae pv tomato DC3000 (Pst DC3000) infection and their combination. Using Affymetrix WT gene 1.0 ST array, global transcriptome profiling of leaves under individual drought stress and pathogen infection was compared with their combination. The results obtained from pathway mapping (KAAS and MAPMAN) demonstrated the modulation in defense pathways in A. thaliana under drought and host pathogen Pst DC3000 infection. Further, our study revealed "tailored" responses under combined stress and the time of occurrence of each stress during their concurrence has shown differences in transcriptome profile. Our results from microarray and RT-qPCR revealed regulation of 20 novel genes uniquely during the stress interaction. This study indicates that plants exposed to concurrent drought and pathogen stress experience a new state of stress. Thus, under frequently changing climatic conditions, time of occurrence of each stress in the interaction defines the plant responses and should thus be studied explicitly. PMID- 27252713 TI - Enhanced Nitrogen Availability in Karst Ecosystems by Oxalic Acid Release in the Rhizosphere. AB - In karst ecosystems, a high level of CaCO3 enhances the stabilization of soil organic matter (SOM) and causes nitrogen (N) and/or phosphorus (P) limitation in plants. Oxalic acid has been suggested to be involved in the nutrient-acquisition strategy of plants because its addition can temporarily relieve nutrient limitation. Therefore, understanding how oxalic acid drives N availability may help support successful vegetation restoration in the karst ecosystems of southwest China. We tested a model suggested by Clarholm et al. (2015) where oxalate reacts with Ca bridges in SOM, thus exposing previously protected areas to enzymatic attacks in a way that releases N for local uptake. We studied the effects of oxalic acid, microbial biomass carbon (MBC), and beta-1,4-N acetylglucosaminidase (NAG) on potential N mineralization rates in rhizosphere soils of four plant species (two shrubs and two trees) in karst areas. The results showed that rhizosphere soils of shrubs grown on formerly deforested land had significantly lower oxalic acid concentrations and NAG activity than that of trees in a 200-year-old forest. The levels of MBC in rhizosphere soils of shrubs were significantly lower than those of trees in the growing season, but the measure of shrubs and trees were similar in the non-growing season; the potential N mineralization rates showed a reverse pattern. Positive relationships were found among oxalic acid, MBC, NAG activity, and potential N mineralization rates for both shrubs and trees. This indicated that oxalic acid, microbes, and NAG may enhance N availability for acquisition by plants. Path analysis showed that oxalic acid enhanced potential N mineralization rates indirectly through inducing microbes and NAG activities. We found that the exudation of oxalic acid clearly provides an important mechanism that allows plants to enhance nutrient acquisition in karst ecosystems. PMID- 27252715 TI - Comparative Chloroplast Genome Analyses of Streptophyte Green Algae Uncover Major Structural Alterations in the Klebsormidiophyceae, Coleochaetophyceae and Zygnematophyceae. AB - The Streptophyta comprises all land plants and six main lineages of freshwater green algae: Mesostigmatophyceae, Chlorokybophyceae, Klebsormidiophyceae, Charophyceae, Coleochaetophyceae and Zygnematophyceae. Previous comparisons of the chloroplast genome from nine streptophyte algae (including four zygnematophyceans) revealed that, although land plant chloroplast DNAs (cpDNAs) inherited most of their highly conserved structural features from green algal ancestors, considerable cpDNA changes took place during the evolution of the Zygnematophyceae, the sister group of land plants. To gain deeper insights into the evolutionary dynamics of the chloroplast genome in streptophyte algae, we sequenced the cpDNAs of nine additional taxa: two klebsormidiophyceans (Entransia fimbriata and Klebsormidium sp. SAG 51.86), one coleocheatophycean (Coleochaete scutata) and six zygnematophyceans (Cylindrocystis brebissonii, Netrium digitus, Roya obtusa, Spirogyra maxima, Cosmarium botrytis and Closterium baillyanum). Our comparative analyses of these genomes with their streptophyte algal counterparts indicate that the large inverted repeat (IR) encoding the rDNA operon experienced loss or expansion/contraction in all three sampled classes and that genes were extensively shuffled in both the Klebsormidiophyceae and Zygnematophyceae. The klebsormidiophycean genomes boast greatly expanded IRs, with the Entransia 60,590 bp IR being the largest known among green algae. The 206,025-bp Entransia cpDNA, which is one of the largest genome among streptophytes, encodes 118 standard genes, i.e., four additional genes compared to its Klebsormidium flaccidum homolog. We inferred that seven of the 21 group II introns usually found in land plants were already present in the common ancestor of the Klebsormidiophyceae and its sister lineages. At 107,236 bp and with 117 standard genes, the Coleochaete IR-less genome is both the smallest and most compact among the streptophyte algal cpDNAs analyzed thus far; it lacks eight genes relative to its Chaetosphaeridium globosum homolog, four of which represent unique events in the evolutionary scenario of gene losses we reconstructed for streptophyte algae. The 10 compared zygnematophycean cpDNAs display tremendous variations at all levels, except gene content. During zygnematophycean evolution, the IR disappeared a minimum of five times, the rDNA operon was broken at four distinct sites, group II introns were lost on at least 43 occasions, and putative foreign genes, mainly of phage/viral origin, were gained. PMID- 27252714 TI - Insights into the Cyanobacterial Deg/HtrA Proteases. AB - Proteins are the main machinery for all living processes in a cell; they provide structural elements, regulate biochemical reactions as enzymes, and are the interface to the outside as receptors and transporters. Like any other machinery proteins have to be assembled correctly and need maintenance after damage, e.g., caused by changes in environmental conditions, genetic mutations, and limitations in the availability of cofactors. Proteases and chaperones help in repair, assembly, and folding of damaged and misfolded protein complexes cost-effective, with low energy investment compared with neo-synthesis. Despite their importance for viability, the specific biological role of most proteases in vivo is largely unknown. Deg/HtrA proteases, a family of serine-type ATP-independent proteases, have been shown in higher plants to be involved in the degradation of the Photosystem II reaction center protein D1. The objective of this review is to highlight the structure and function of their cyanobacterial orthologs. Homology modeling was used to find specific features of the SynDeg/HtrA proteases of Synechocystis sp. PCC 6803. Based on the available data concerning their location and their physiological substrates we conclude that these Deg proteases not only have important housekeeping and chaperone functions within the cell, but also are needed for remodeling the cell exterior. PMID- 27252716 TI - Within-Leaf Nitrogen Allocation in Adaptation to Low Nitrogen Supply in Maize during Grain-Filling Stage. AB - Nitrogen (N) plays a vital role in photosynthesis and crop productivity. Maize plants may be able to increase physiological N utilization efficiency (NUtE) under low-N stress by increasing photosynthetic rate (P n) per unit leaf N, that is, photosynthetic N-use efficiency (PNUE). In this study, we analyzed the relationship between PNUE and N allocation in maize ear-leaves during the grain filling stage under low N (no N application) and high N (180 kg N ha(-1)) in a 2 year field experiment. Under low N, grain yield decreased while NUtE increased. Low-N treatment reduced the specific N content of ear leaves by 38% without significant influencing P n, thereby increasing PNUE by 54%. Under low-N stress, maize plants tended to invest relatively more N into bioenergetics to sustain electron transport. In contrast, N allocated to chlorophyll and light-harvesting proteins was reduced to control excess electron production. Soluble proteins were reduced to shrink the N storage reservoir. We conclude that optimization of N allocation within leaves is a key adaptive mechanism to maximize P n and crop productivity when N is limited during the grain-filling stage in maize under low N conditions. PMID- 27252717 TI - Tetraploidy Enhances Boron-Excess Tolerance in Carrizo Citrange (Citrus sinensis L. Osb. * Poncirus trifoliata L. Raf.). AB - Tetraploidy modifies root anatomy which may lead to differentiated capacity to uptake and transport mineral elements. This work provides insights into physiological and molecular characters involved in boron (B) toxicity responses in diploid (2x) and tetraploid (4x) plants of Carrizo citrange (Citrus sinensis L. Osb. * Poncirus trifoliata L. Raf.), a widely used citrus rootstock. With B excess, 2x plants accumulated more B in leaves than 4x plants, which accounted for their higher B uptake and root-to-shoot transport rates. Ploidy did not modify the expression of membrane transporters NIP5 and BOR1 in roots. The cellular allocation of B excess differed between ploidy levels in the soluble fraction, which was lower in 4x leaves, while cell wall-linked B was similar in 2x and 4x genotypes. This correlates with the increased damage and stunted growth recorded in the 2x plants. The 4x roots were found to have fewer root tips, shorter specific root length, longer diameter, thicker exodermis and earlier tissue maturation in root tips, where the Casparian strip was detected at a shorter distance from the root apex than in the 2x roots. The results presented herein suggest that the root anatomical characters of the 4x plants play a key role in their lower B uptake capacity and root-to-shoot transport. HIGHLIGHTS: Tetraploidy enhances B excess tolerance in citrange CarrizoExpression of NIP5 and BOR1 transporters and cell wall-bounded B are similar between ploidiesB tolerance is attributed to root anatomical modifications induced by genome duplicationThe rootstock 4x citrange carrizo may prevent citrus trees from B excess. PMID- 27252718 TI - Increasing Confidence of Proteomics Data Regarding the Identification of Stress Responsive Proteins in Crop Plants. PMID- 27252720 TI - Morphology, Structure, and Ontogeny of Trichomes of the Grape Genus (Vitis, Vitaceae). AB - Trichomes are widely distributed on surfaces of different organs in the grape genus Vitis and are of taxonomic utility. To explore the morphology, structure and ontogeny of Vitis trichomes, we investigated the diversity and distribution of trichomes in 34 species of Vitis. Two main types of trichomes in Vitis are documented: non-glandular and glandular. Within non-glandular trichomes, ribbon and simple trichomes are found on different vegetative plant organs. The morphology and ontogeny of these types of trichomes are further examined with light microscopy and scanning electron microscopy. The ultrastructure of the glandular trichomes is explored with transmission electron microscopy. The ribbon trichomes are twisted, greatly elongated and unicellular, and this trichome type may be a morphological synapomorphy of Vitis and its closest tropical relative Ampelocissus and Pterisanthes in Vitaceae. The simple trichomes are documented in most species sampled in the genus. The glandular trichomes are multicellular, non vascularized and composed of both epidermis and subjacent layers. We show that prickles occurring along the stems and petioles of Vitis davidii are modified glandular trichomes. We observed that glandular trichomes of V. romanetii secrete mucilage and volatile substances which trap insectes on the glands. Transmission electron microscopy indicates that metabolic products accumulate in vacuoles, the cytoplasm and intercellular spaces. We infer that glandular trichomes and young prickles are involved in the secretion of these metabolic products and the intercellular spaces may be the places of temporary storage of these secretions. PMID- 27252719 TI - Recent Advances in Genome Editing Using CRISPR/Cas9. AB - The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is a versatile tool for genome engineering that uses a guide RNA (gRNA) to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM) puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding. PMID- 27252721 TI - Timing of False Ring Formation in Pinus halepensis and Arbutus unedo in Southern Italy: Outlook from an Analysis of Xylogenesis and Tree-Ring Chronologies. AB - Mediterranean tree rings are characterized by intra-annual density fluctuations (IADFs) due to partly climate-driven cambial activity. IADFs are used as structural signals to gain information on relations between environmental conditions and eco-physiological processes during xylogenesis, with intra-annual resolution. To reach an unbiased synchronization of the IADF position within tree rings and seasonal fluctuations in environmental conditions, it is necessary to know the timing of cambial activity and wood formation, which are species- and site-specific processes. We applied the microcoring technique to analyze xylogenesis in Pinus halepensis and Arbutus unedo. To the best of our knowledge, this is the first attempt to study xylogenesis in a hardwood species forming frequent IADFs. Both species co-occur at a site in southern Italy characterized by a Mediterranean climate. To facilitate tree-ring dating and identification of IADFs, we performed traditional dendroecological analysis. We analyzed xylogenesis during summer, which is considered a constraint for xylogenesis and a trigger for IADF formation. We followed the different phases of cell development in the current wood increment with the aim of evaluating whether and which type of IADFs were formed. We additionally analyzed the same phases again in September and in winter to verify the possible formation of IADFs in fall and whether cell production and differentiation was completed by the end of the calendar year. Both species formed the same type of IADFs (earlywood-like cells within latewood), due to temporary growth restoration triggered by rain events during the period of summer drought. At the end of the calendar year, no cells in the phases of enlargement and secondary cell wall deposition occurred. A. unedo was more sensitive than P. halepensis because IADFs were formed earlier in the season and were more frequent in the tree-ring series. The dendro-anatomical approach, combining analysis of tree-ring series and of xylogenesis, helped to detect the period of IADF formation in the two species. Results are discussed in functional terms, highlighting the environmental conditions triggering IADFs, and also in methodological terms, evaluating the applicability of xylogenesis analysis in Mediterranean woods, especially when the formation of IADFs is not uniform around the stem. PMID- 27252722 TI - Different Growth Promoting Effects of Endophytic Bacteria on Invasive and Native Clonal Plants. AB - The role of the interactions between endophytes and alien plants has been unclear yet in plant invasion. We used a completely germ-free culture system to quantify the plant growth-promoting (PGP) effects of endophytic bacteria Bacillus sp. on aseptic seedlings of Wedelia trilobata and of its native clonal congener W. chinensis. The endophytic bacteria did not affect the growth of W. chinensis, but they significantly promoted the growth of W. trilobata. With the PGP effects of endophytic bacteria, relative change ratios of the clonal traits and the ramets' growth traits of W. trilobata were significantly greater than those of W. chinensis. Our results indicate that the growth-promoting effects of endophytes may differ between invasive and native clonal plants, and the endophytes of invasive plant may be host-specific to facilitate plant invasion. PMID- 27252723 TI - Proteomic Dissection of Endosperm Starch Granule Associated Proteins Reveals a Network Coordinating Starch Biosynthesis and Amino Acid Metabolism and Glycolysis in Rice Endosperms. AB - Starch biosynthesis and starch granule packaging in cereal endosperms involve a coordinated action of starch biosynthesis enzymes and coordination with other metabolisms. Because directly binding to starch granules, starch granule associated proteins (SGAPs) are essential to understand the underlying mechanisms, however the information on SGAPs remains largely unknown. Here, we dissected developmentally changed SGAPs from developing rice endosperms from 10 to 20 days after flowering (DAF). Starch granule packaging was not completed at 10 DAF, and was finished in the central endosperm at 15 DAF and in the whole endosperm at 20 DAF. Proteomic analysis with two-dimensional differential in-gel electrophoresis and mass spectrometry revealed 115 developmentally changed SGAPs, representing 37 unique proteins. 65% of the unique proteins had isoforms. 39% of the identified SGAPs were involved in starch biosynthesis with main functions in polyglucan elongation and granule structure trimming. Almost all proteins involved in starch biosynthesis, amino acid biosynthesis, glycolysis, protein folding, and PPDK pathways increased abundance as the endosperm developed, and were predicted in an interaction network. The network represents an important mechanism to orchestrate carbon partitioning among starch biosynthesis, amino acid biosynthesis and glycolysis for efficient starch and protein storage. These results provide novel insights into mechanisms of starch biosynthesis and its coordination with amino acid metabolisms and glycolysis in cereal endosperms. PMID- 27252724 TI - ABA Suppresses Botrytis cinerea Elicited NO Production in Tomato to Influence H2O2 Generation and Increase Host Susceptibility. AB - Abscisic acid (ABA) production has emerged a susceptibility factor in plant pathogen interactions. This work examined the interaction of ABA with nitric oxide (NO) in tomato following challenge with the ABA-synthesizing pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production - an established mediator of defense against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME) suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS) generation but this was reduced in both L NAME and ABA-treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production. PMID- 27252725 TI - Molecular Cloning and Characterization of Four Genes Encoding Ethylene Receptors Associated with Pineapple (Ananas comosus L.) Flowering. AB - Exogenous ethylene, or ethephon, has been widely used to induce pineapple flowering, but the molecular mechanism behind ethephon induction is still unclear. In this study, we cloned four genes encoding ethylene receptors (designated AcERS1a, AcERS1b, AcETR2a, and AcETR2b). The 5' flanking sequences of these four genes were also cloned by self-formed adaptor PCR and SiteFinding-PCR, and a group of putative cis-acting elements was identified. Phylogenetic tree analysis indicated that AcERS1a, AcERS1b, AcETR2a, and AcETR2b belonged to the plant ERS1s and ETR2/EIN4-like groups. Quantitative real-time PCR showed that AcETR2a and AcETR2b (subfamily 2) were more sensitive to ethylene treatment compared with AcERS1a and AcERS1b (subfamily 1). The relative expression of AcERS1b, AcETR2a, and AcETR2b was significantly increased during the earlier period of pineapple inflorescence formation, especially at 1-9 days after ethylene treatment (DAET), whereas AcERS1a expression changed less than these three genes. In situ hybridization results showed that bract primordia (BP) and flower primordia (FP) appeared at 9 and 21 DAET, respectively, and flowers were formed at 37 DAET. AcERS1a, AcERS1b, AcETR2a, and AcETR2b were mainly expressed in the shoot apex at 1-4 DAET; thereafter, with the appearance of BP and FP, higher expression of these genes was found in these new structures. Finally, at 37 DAET, the expression of these genes was mainly focused in the flower but was also low in other structures. These findings indicate that these four ethylene receptor genes, especially AcERS1b, AcETR2a, and AcETR2b, play important roles during pineapple flowering induced by exogenous ethephon. PMID- 27252726 TI - Emerging Insights on Brazilian Pepper Tree (Schinus terebinthifolius) Invasion: The Potential Role of Soil Microorganisms. AB - Invasive plant species constitute a major ecological and economic problem worldwide, often distorting trophic levels and ecosystem balance. Numerous studies implicate factors ranging from environmental plasticity, competition for nutrient and space, and allelopathy in the success of invasive species in general. The Brazilian Pepper tree (BP) was introduced to the United States in the 1800s and has since become a category one invasive plant in Florida. It has aggressively spread to about 3000 km(2) of terrestrial surface, fueled in part by the prevalence of the hybrid genotypes and environmental perturbations. It displays some of the well-established invasive mechanisms but there is a serious dearth of knowledge on the plant-microbe-soil interactions and whether the rhizobiome plays any roles in the displacement of native flora and the range expansion of BP. Several control measures, including chemical, mechanical, and biological antagonism have been used with limited success while restoration of natives in soils from which BP was removed has proved problematic partly due to a poorly understood phenomenon described as the "BP legacy effect." Emerging evidence suggests that allelopathy, selective recruitment of beneficial soil microbes, disruption of microbial community structure and alteration of nutrient cycling, exhibited by many other invasive plant species may also be involved in the case of BP. This brief review discusses the well-established BP invasion mechanisms and highlights the current understanding of the molecular, below ground processes. It also points out the gaps in studies on the potential role of microbial interactions in the success of BP invasion. These hitherto poorly studied mechanisms could further explain the aggressive spread of BP and could potentially contribute significantly to effective control measures and enable appropriate strategies for restoring native plants. The review advocates for the use of cutting-edge techniques in advancing the plant microbiome science. Ultimately, comparing metagenomic analyses of the rhizobiome of invasive plants grown in native and non-native soils could lead to a better understanding of the microbial determinants of biotic resistance, potentially empowering environmental managers with some predictive power of future trends of plant invasion. PMID- 27252727 TI - Corrigendum: Melatonin: Current Status and Future Perspectives in Plant Science. AB - [This corrects the article on p. 1230 in vol. 6, PMID: 26793210.]. PMID- 27252728 TI - Transcriptome Profiling of Buffalograss Challenged with the Leaf Spot Pathogen Curvularia inaequalis. AB - Buffalograss (Bouteloua dactyloides) is a low maintenance U. S. native turfgrass species with exceptional drought, heat, and cold tolerance. Leaf spot caused by Curvularia inaequalis negatively impacts buffalograss visual quality. Two leaf spot susceptible and two resistant buffalograss lines were challenged with C. inaequalis. Samples were collected from treated and untreated leaves when susceptible lines showed symptoms. Transcriptome sequencing was done and differentially expressed genes were identified. Approximately 27 million raw sequencing reads were produced per sample. More than 86% of the sequencing reads mapped to an existing buffalograss reference transcriptome. De novo assembly of unmapped reads was merged with the existing reference to produce a more complete transcriptome. There were 461 differentially expressed transcripts between the resistant and susceptible lines when challenged with the pathogen and 1552 in its absence. Previously characterized defense-related genes were identified among the differentially expressed transcripts. Twenty one resistant line transcripts were similar to genes regulating pattern triggered immunity and 20 transcripts were similar to genes regulating effector triggered immunity. There were also nine up regulated transcripts in resistance lines which showed potential to initiate systemic acquired resistance (SAR) and three transcripts encoding pathogenesis related proteins which are downstream products of SAR. This is the first study characterizing changes in the buffalograss transcriptome when challenged with C. inaequalis. PMID- 27252729 TI - Use of Agrobacterium rhizogenes Strain 18r12v and Paromomycin Selection for Transformation of Brachypodium distachyon and Brachypodium sylvaticum. AB - The genetic transformation of monocot grasses is a resource intensive process, the quality and efficiency of which is dependent in part upon the method of DNA introduction, as well as the ability to effectively separate transformed from wildtype tissue. Agrobacterium-mediated transformation of Brachypodium has relied mainly on Agrobacterium tumefaciens strain AGL1. Currently the antibiotic hygromycin B has been the selective agent of choice for robust identification of transgenic calli in Brachypodium distachyon and Brachypodium sylvaticum but few other chemicals have been shown to work as well for selection of transgenic Brachypodium cells in tissue culture. This study demonstrates that Agrobacterium rhizogenes strain 18r12v and paromomycin selection can be successfully used for the efficient generation of transgenic B. distachyon and B. sylvaticum. Additionally we observed that the transformation rates were similar to or higher than those obtained with A. tumefaciens strain AGL1 and hygromycin selection. The A. rhizogenes strain 18r12v harboring the pARS1 binary vector and paromomycin selection is an effective means of generating transgenic Brachypodium plants. This novel approach will facilitate the transgenic complementation of T-DNA knockout mutants of B. distachyon which were created using hygromycin selection, as well as aid the implementation of more complex genome manipulation strategies which require multiple rounds of transformation. PMID- 27252730 TI - Identification of Candidate Transcriptional Regulators of Epidermal Transfer Cell Development in Vicia faba Cotyledons. AB - Transfer cells (TCs) are anatomically-specialized cells formed at apoplasmic symplasmic bottlenecks in nutrient transport pathways in plants. TCs form invaginated wall ingrowths which provide a scaffold to amplify plasma membrane surface area and thus increase the density of nutrient transporters required to achieve enhanced nutrient flow across these bottlenecks. Despite their importance to nutrient transport in plants, little is known of the transcriptional regulation of wall ingrowth formation. Here, we used RNA-Seq to identify transcription factors putatively involved in regulating epidermal TC development in cotyledons of Vicia faba. Comparing cotyledons cultured for 0, 3, 9, and 24 h to induce trans-differentiation of epidermal TCs identified 43 transcription factors that showed either epidermal-specific or epidermal-enhanced expression, and 10 that showed epidermal-specific down regulation. Members of the WRKY and ethylene-responsive families were prominent in the cohort of transcription factors showing epidermal-specific or epidermal-enhanced expression, consistent with the initiation of TC development often representing a response to stress. Members of the MYB family were also prominent in these categories, including orthologs of MYB genes involved in localized secondary wall deposition in Arabidopsis thaliana. Among the group of transcription factors showing down regulation were various homeobox genes and members of the MADs-box and zinc finger families of poorly defined functions. Collectively, this study identified several transcription factors showing expression characteristics and orthologous functions that indicate likely participation in transcriptional regulation of epidermal TC development in V. faba cotyledons. PMID- 27252731 TI - Promoting Roles of Melatonin in Adventitious Root Development of Solanum lycopersicum L. by Regulating Auxin and Nitric Oxide Signaling. AB - Melatonin (MT) plays integral roles in regulating several biological processes including plant growth, seed germination, flowering, senescence, and stress responses. This study investigated the effects of MT on adventitious root formation (ARF) of de-rooted tomato seedlings. Exogenous MT positively or negatively influenced ARF, which was dependent on the concentration of MT application. In the present experiment, 50 MUM MT showed the best effect on inducing ARF. Interestingly, exogenous MT promoted the accumulation of endogenous nitric oxide (NO) by down-regulating the expression of S-nitrosoglutathione reductase (GSNOR). To determine the interaction of MT and NO in ARF, MT synthesis inhibitor p-chlorophenylalanine, NO scavenger 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide potassium salt as well as GSNOR overexpression plants with low NO levels were used. The function of MT was removed by NO scavenger or GSNOR-overexpression plants. However, application of MT synthesis inhibitor did little to abolish the function of NO. These results indicate that NO, as a downstream signal, was involved in the MT-induced ARF. Concentrations of indole-3-acetic acid and indole-3-butyric acid, as well as the expression of several genes related to the auxin signaling pathway (PIN1, PIN3, PIN7, IAA19, and IAA24), showed that MT influenced auxin transport and signal transduction as well as auxin accumulation through the NO signaling pathway. Collectively, these strongly suggest that elevated NO levels resulting from inhibited GSNOR activity and auxin signaling were involved in the MT-induced ARF in tomato plants. This can be applied in basic research and breeding. PMID- 27252732 TI - Characterization of an Autophagy-Related Gene MdATG8i from Apple. AB - Nutrient deficiencies restrict apple (Malus sp.) tree growth and productivity in Northwest China. The process of autophagy, a conserved degradation pathway in eukaryotic cells, has important roles in nutrient-recycling and helps improve plant performance during periods of nutrient-starvation. Little is known about the functioning of autophagy-related genes (ATGs) in apple. In this study, one of the ATG8 gene family members MdATG8i was isolated from Malus domestica. MdATG8i has conserved putative tubulin binding sites and ATG7 interaction domains. A 1865 bp promoter region cloned from apple genome DNA was predicated to have cis regulatory elements responsive to light, environmental stresses, and hormones. MdATG8i transcriptions were induced in response to leaf senescence, nitrogen depletion, and oxidative stress. At cellular level, MdATG8i protein was expressed in the nucleus and cytoplasm of onion epidermal cells. Yeast two-hybrid tests showed that MdATG8i could interact with MdATG7a and MdATG7b. In Arabidopsis, its heterologous expression was associated with enhanced vegetative growth, leaf senescence, and tolerance to nitrogen- and carbon-starvation. MdATG8i overexpressing "Orin" apple callus lines also displayed improved tolerance to nutrient-limited conditions. Our results demonstrate that MdATG8i protein could function in autophagy in a conserved way, as a positive regulator in the response to nutrient-starvation. PMID- 27252733 TI - Cloning, Functional Characterization, and Catalytic Mechanism of a Bergaptol O Methyltransferase from Peucedanum praeruptorum Dunn. AB - Coumarins are main active components of Peucedanum praeruptorum Dunn. Among them, methoxylated coumarin compound, such as bergapten, xanthotoxin, and isopimpinellin, has high officinal value and plays an important role in medicinal field. However, major issues associated with the biosynthesis mechanism of coumarins remain unsolved and no corresponding enzyme has been cloned from P. praeruptorum. In this study, a local BLASTN program was conducted to find the candidate genes from P. praeruptorum transcriptome database using the nucleotide sequence of Ammi majus bergaptol O-methyltransferase (AmBMT, GenBank accession No: AY443006) as a template. As a result, a 1335 bp full-length of cDNA sequence which contains an open reading frame of 1080 bp encoding a BMT polypeptide of 359 amino acids was obtained. The recombinant protein was functionally expressed in Escherichia coli and displayed an observed activity to bergaptol. In vitro experiments show that the protein has narrow substrate specificity for bergaptol. Expression profile indicated that the cloned gene had a higher expression level in roots and can be induced by methyl jasmonate (MeJA). Subcellular localization analysis showed that the BMT protein was located in cytoplasm in planta. Homology modeling and docking based site-directed mutagenesis have been employed to investigate the amino acid residues in BMT required for substrate binding and catalysis. Conservative amino acid substitutions at residue H264 affected BMT catalysis, whereas substitutions at residues F171, M175, D226, and L312 affected substrate binding. The systemic study summarized here will enlarge our knowledge on OMTs and provide useful information in investigating the coumarins biosynthesis mechanism in P. praeruptorum. PMID- 27252734 TI - Elementary Vectors and Conformal Sums in Polyhedral Geometry and their Relevance for Metabolic Pathway Analysis. AB - A fundamental result in metabolic pathway analysis states that every flux mode can be decomposed into a sum of elementary modes. However, only a decomposition without cancelations is biochemically meaningful, since a reversible reaction cannot have different directions in the contributing elementary modes. This essential requirement has been largely overlooked by the metabolic pathway community. Indeed, every flux mode can be decomposed into elementary modes without cancelations. The result is an immediate consequence of a theorem by Rockafellar which states that every element of a linear subspace is a conformal sum (a sum without cancelations) of elementary vectors (support-minimal vectors). In this work, we extend the theorem, first to "subspace cones" and then to general polyhedral cones and polyhedra. Thereby, we refine Minkowski's and Caratheodory's theorems, two fundamental results in polyhedral geometry. We note that, in general, elementary vectors need not be support-minimal; in fact, they are conformally non-decomposable and form a unique minimal set of conformal generators. Our treatment is mathematically rigorous, but suitable for systems biologists, since we give self-contained proofs for our results and use concepts motivated by metabolic pathway analysis. In particular, we study cones defined by linear subspaces and nonnegativity conditions - like the flux cone - and use them to analyze general polyhedral cones and polyhedra. Finally, we review applications of elementary vectors and conformal sums in metabolic pathway analysis. PMID- 27252735 TI - From the Editor-in-Chief. PMID- 27252736 TI - Algodystrophy: complex regional pain syndrome and incomplete forms. AB - The algodystrophy, also known as complex regional pain syndrome (CRPS), is a painful disease characterized by erythema, edema, functional impairment, sensory and vasomotor disturbance. The diagnosis of CRPS is based solely on clinical signs and symptoms, and for exclusion compared to other forms of chronic pain. There is not a specific diagnostic procedure; careful clinical evaluation and additional test should lead to an accurate diagnosis. There are similar forms of chronic pain known as bone marrow edema syndrome, in which is absent the history of trauma or triggering events and the skin dystrophic changes and vasomotor alterations. These incomplete forms are self-limited, and surgical treatment is generally not needed. It is still controversial, if these forms represent a distinct self-limiting entity or an incomplete variant of CRPS. In painful unexplained conditions such as frozen shoulder, post-operative stiff shoulder or painful knee prosthesis, the algodystrophy, especially in its incomplete forms, could represent the cause. PMID- 27252737 TI - Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity! AB - Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID- 27252738 TI - Differences in monthly variation, cause, and place of injury between femoral neck and trochanteric fractures: 6-year survey (2008-2013) in Kyoto prefecture, Japan. AB - BACKGROUND: The incidence of femoral neck and trochanteric fractures reportedly differ by age and regionality. We investigated differences in monthly variations of the occurrence of femoral neck and trochanteric fractures as well as place and cause of injury in the Kyoto prefecture over a 6-year period. METHODS: Fracture type (neck or trochanteric fracture), age, sex, place of injury, and cause of injury were surveyed among patients aged >= 65 years with hip fractures that occurred between 2008 and 2013 who were treated in 1 of 13 participating hospitals (5 in an urban area and 8 in a rural area). The proportion of sick beds in the participating hospitals was 24.7% (4,151/16,781). Monthly variations in the number of patients were investigated in urban and rural areas in addition to the entire Kyoto prefecture. Place of injury was classified as indoors or outdoors, and cause of injury was categorized as simple fall, accident, or uncertain. RESULTS: There were 2,826 patients with neck fractures (mean age, 82.1 years) and 3,305 patients with trochanteric fractures (mean age, 85.0 years). There were similarities in the monthly variation of the number of fractures in addition to the place and cause of injury between neck and trochanteric fractures. Indoors (approximately 74%) and simple falls (approximately 78%) were the primary place and cause of injury, respectively. The place of injury was not significantly different by fracture type with each age group. Significantly more patients with neck fracture had "uncertain" as the cause of injury than trochanteric fracture in all age groups. CONCLUSIONS: Based on the results of the present study, the injury pattern might not have a great effect on the susceptibility difference between neck and trochanteric fractures. PMID- 27252739 TI - Comparison of the effects of eldecalcitol with either raloxifene or bisphosphonate on serum tartrate resistant acid phosphatase-5b, a bone resorption marker, in postmenopausal osteoporosis. AB - OBJECTIVE: This study analyzes whether concomitant raloxifene (RLX) or bisphosphonates (BP) plus eldecalcitol (ELD) has excessive suppressive effects on a bone resorption marker during the first 6 months of treatment in postmenopausal women in real-world setting. METHODS: 285 postmenopausal osteoporotic patients who had been treated with RLX or BP plus ELD were evaluated the bone resorption marker, serum tartrate resistant acid phosphatase-5b (TRACP-5b), during the first 6 months of treatment. RESULTS: In drug-naive group (not received osteoporosis medications before the administration, n=70), the concomitant RLX or BP with ELD significantly decreased levels of TRACP-5b without severe suppression. In vitamin D switch group [RLX or BP plus alfacalcidol (ALF) and then switched to RLX or BP plus ELD, n=215], the replacing ALF with ELD further and significantly decreased TRACP-5b and tertile analyses based on baseline values were significantly decreased far more in the highest, compared with the lowest tertile in the ELD+RLX and ELD+BP groups. CONCLUSION: ELD combined with RLX or BP administered for 6 months to postmenopausal women with osteoporosis who were drug-naive or who had switched medications significantly reduced and maintained TRACP-5b values within the reference range. PMID- 27252740 TI - Use of MR-based trabecular bone microstructure analysis at the distal radius for osteoporosis diagnostics: a study in post-menopausal women with breast cancer and treated with aromatase inhibitor. AB - PURPOSE: Treatment with aromatase inhibitor (AI) is recommended for post menopausal women with hormone-receptor positive breast cancer. However, AI therapy is known to induce bone loss leading to osteoporosis with an increased risk for fragility fractures. The purpose of this study was to investigate whether changes of magnetic resonance (MR)-based trabecular bone microstructure parameters as advanced imaging biomarker can already be detected in subjects with AI intake but still without evidence for osteoporosis according to dual energy X ray absorptiometry (DXA)-based bone mineral density (BMD) measurements as current clinical gold standard. METHODS: Twenty-one postmenopausal women (62+/-6 years of age) with hormone-receptor positive breast cancer, ongoing treatment with aromatase inhibitor for 23+/-15 months, and no evidence for osteoporosis (current DXA T-score greater than -2.5) were recruited for this study. Eight young, healthy women (24+/-2 years of age) were included as controls. All subjects underwent 3 Tesla magnetic resonance imaging (MRI) of the distal radius to assess the trabecular bone microstructure. RESULTS: Trabecular bone microstructure parameters were not significantly (p>0.05) different between subjects with AI intake and controls, including apparent bone fraction (0.42+/-0.03 vs. 0.42+/ 0.05), trabecular number (1.95+/-0.10 mm(-1) vs 1.89+/-0.15 mm(-1)), trabecular separation (0.30+/-0.03 mm vs 0.31+/-0.06 mm), trabecular thickness (0.21+/-0.01 mm vs 0.22+/-0.02 mm), and fractal dimension (1.70+/-0.02 vs. 1.70+/-0.03). CONCLUSION: These findings suggest that the initial deterioration of trabecular bone microstructure as measured by MRI and BMD loss as measured by DXA occur not sequentially but rather simultaneously. Thus, the use of MR-based trabecular bone microstructure assessment is limited as early diagnostic biomarker in this clinical setting. PMID- 27252741 TI - Clodronate news of efficacy in osteoporosis. AB - Clodronate belongs to Bisphosphonates family and it has been studied especially for osteoporosis treatment, Paget's disease, osteolytic metastases, hypercalcemia malignancy and some childhood skeletal diseases. Besides the osteoporosis treatment, it has been successfully used for treating tumoral osteolysis and for bone localization of multiple myeloma, hypercalcemia malignancy, primary hyperparathyroidism, Paget's disease and algodystrophy. Filipponi study showed a statistically significant reduction of the incidence of vertebral fractures after 4 years of treatment with clodronate, intravenously administered at a dose of 200 mg every three weeks. Frediani study, published in 2003 on BONE, proved the clodronate efficacy in the prevention of fractures caused by glucocorticoid induced osteoporosis (GIO). Clodronate doses of 800 mg/day per os and 100 mg i.m./week are substantially equivalent, because the oral absorption is about 1,9%. A higher efficacy on BMD was documented in various works, especially in cohorts of patients with a greater fracture risk, using higher doses (1600 mg per os). This has led to the hypothesis of using clodronate 200 mg i.m. formulation. Clodronate is an osteoporosis drug that can be assumed in different doses (100 mg i.m./week, clodronate 200 mg i.m. every 2 weeks) considering the risk band, identified by algorithms (FRAX o DeFRA), by BMD and by the presence of at least one risk factor. That means that it is possible to envisage a differentiated use of clodronate adapting the doses to the fracture risk and to the severity of pain symptoms, thus promoting a greater adherence to the therapy. To conclude clodronate is helpful in reducing fracture risk, is safe, well tolerated, and has a good rate cost/effectiveness in patients with fracture risk over 7% established with FRAX. PMID- 27252742 TI - Hyaluronan viscosupplementation: state of the art and insight into the novel cooperative hybrid complexes based on high and low molecular weight HA of potential interest in osteoarthritis treatment. AB - Osteoarthritis (OA) represents a group of chronic, painful, disabling conditions affecting synovial joints. It is characterized by degeneration of articular cartilage, alterations of peri-articular and subchondral bone, low-grade synovial inflammation (synovitis). Despite OA is commonly described as a non-inflammatory disease, it is known that its progression and the subsequent increment of symptoms correlate to the production of inflammatory factors that induce the secretion of enzymes responsible for cartilage degradation. In clinical practice, to alleviate pain and stiffness, not only during acute phases but also as maintenance therapy, intra-articular injections of corticosteroids or similar drugs are used, besides it is well diffused the viscosupplementation procedure based on hyaluronan gel. There are many different products containing high molecular weight linear HA or cross-linked derivatives, however the novelty in the field consist in the hybrid cooperative complexes derived from high and low molecular weight HA through a patented processing. This technique permit to double the amount of HA delivered to the injured site without increasing the injected volume, beside in vitro assay on human chondrocytes suggested hybrid complexes as effective in the modulation of several inflammatory cytokines in joints. PMID- 27252743 TI - Atraumatic intracapsular neck of femur fractures after prolonged bisphosphonate treatment: a new atypical variant? AB - We present 2 cases of elderly females presenting with atraumatic, near-vertical (Pauwells grade 3), intracapsular neck of femur fractures. Following diagnosis of osteoporosis on DEXA scans, they had received alendronic acid for 7 and 10 years respectively. Routine blood tests and serum estimations of calcium, vitamin-D and thyroid-stimulating hormone, done at admission, were within the normal ranges. These patients were managed with a hemiarthroplasty and a dynamic hip screw (DHS) respectively, following discontinuation of bisphosphonates. We present these 2 cases in light of emerging evidence that associates long-term bisphosphonate use with atypical low energy femoral fractures. Only subtrochanteric/diaphyseal fractures have been reported to date. We present a new variant of atypical femoral neck fractures in metaphyseal bone related to prolonged bisphosphonate therapy. PMID- 27252744 TI - Surgical prevention of femoral neck fractures in elderly osteoporotic patients. A literature review. AB - Fragility fractures of the femur are one of the major causes of morbidity and mortality worldwide. The incidence of new contralateral hip fractures in elderly osteoporotic patients ranges from 7 to 12% within 2 years after the first fracture. Secondary prevention can be divided in: pharmacological therapy based on the prescription of anti-osteoporotic drugs with different mechanism of action and non-pharmacological therapy which is based on modification of environmental risk factors, on a healthy diet with daily supplements of calcium and vitamin D and calcium and on the use of hip protectors. Recently a new form of prevention is becoming achievable: surgical prevention; the rationale of surgical reinforcement is the need to increase the resistance of the femoral neck to the compression and distraction forces acting on it. In this paper we analyse all the experimental and "on the market" device available for the surgical prevention of femoral neck fracture. PMID- 27252745 TI - Immobilization induced hypercalcemia. AB - Immobilization hypercalcemia is an uncommon diagnosis associated with increased bone remodeling disorders and conditions associated with limited movement such as medullar lesions or vascular events. Diagnosis requires an extensive evaluation to rule out other causes of hypercalcemia. This is a report of a woman with prolonged immobilization who presented with severe hypercalcemia. This case contributes to identification of severe hypercalcemia as a result of immobility and the description of bone metabolism during this state. PMID- 27252746 TI - Detection of melorheostosis in a young lady with upper limb pain on Three Phase Bone Scintigram/SPECT-CT. AB - Melorheostosis is a benign, noninheritable bone dysplasia characterized by its classic radiographic features of dense, flowing hyperostosis. It frequently affects one limb, usually the lower extremity and rarely the axial skeleton. A 26 year-old lady with obesity, polycystic ovarian syndrome and scalp dandruff presented with a long standing history of upper extremity pain and inability to adduct the arm completely. A Tc-99m MDP whole body and SPECT/CT scan performed for suspected fibrous dysplasia showed increased radiotracer uptake in densely sclerotic humeral and radial melorheostosis. This case highlighted the role of SPECT/CT imaging in this rare condition. PMID- 27252747 TI - An unusual case of hypercalcemia in a patient of concomitant hypoparathyroidism and celiac disease. AB - Milk alkali syndrome has shown resurgence with increase in use of (prescription or non prescription) calcium supplements. Cases of iatrogenic vitamin D intoxication has also increased due to increasing use of high doses of injectable vitamin D formulations by physicians, surgeons, orthopaedicians, gynecologists and other specialties inadvertently. Here, we present an unusual case of a 17 year-old boy who presented with iatrogenic hypercalcemia as a result of combination of milk alkali syndrome with vitamin D intoxication despite being a case of hypoparathyroidism and concomitantly suffering from celiac disease. PMID- 27252748 TI - Ossification of the cervical ligamentum flavum and osseous brown tumor: late manifestations of primary hyperparathyroidism misdiagnosed in a case of parathyroid carcinoma. AB - Parathyroid carcinoma represents an extremely rare neoplasm with diverse clinical manifestations. Herein we aimed at presenting an unique case of a young patient with late manifestations of parathyroid cancer and reviewing the relevant literature. A 45-year-old male patient presented in the Outpatient Clinic with an episode of nephrolithiasis. His personal medical history includes: recurrent episodes of nephrolithiasis, laminectomy in the cervical spine due to ossification of the cervical ligamentum flavum and surgical resection of a giant cell tumor of the brain. Laboratory testing revealed findings of primary hyperparathyroidism (serum calcium 16,0 mmol/l phosphorus 1,46 mg/dl and parathyroid hormone/PTH 8560 pg/ml). Neck ultrasound and technetium-99 m sestamibi scan were performed showing a parathyroid tumor. Due to the persistently high serum calcium and PTH levels, the high alkaline phosphatase levels (440 IU/L) and the late manifestations of HPT, surgical excision of the tumor was performed. The tumor was identified as parathyroid carcinoma. Immediately after surgery serum calcium and phosphorus levels were normalized. The patient is on a regular follow-up program with no signs of recurrence or metastasis one year after the excision. We describe the coexistence of rare late manifestations of HPT, which had not been adequately investigated at their onset in this young patient. Therefore, increased awareness is needed in order to recognize and further investigate signs or symptoms of HPT. PMID- 27252749 TI - Atypical femoral fractures bilaterally in a patient receiving bisphosphonate: a case report. AB - Atypical femoral fractures are often associated with prolonged bisphosphonate use. The American Society for Bone and Mineral Research (ASBMR) has set the diagnosis criteria for atypical subtrochanteric and diaphyseal femoral fractures by classifying them according to their major and minor criteria. Prolonged bisphosphonate use is correlated with AFF, but the pathogenetic mechanism that causes this kind of fracture has not been defined yet. We describe simultaneous bilaterally femoral fractures in a 76-year-old woman. PMID- 27252750 TI - Asymmetrical bone loss in a patient with poliomyelitis: an indication for anti osteoporotic therapy. AB - BACKGROUND: Poliomyelitis survivors suffer from post-myelitic complications including osteoporosis that are often overlooked. METHODS: We report a case of a 49-year-old lady with history of poliomyelitis with resultant flaccid paralysis of the involved limb. RESULTS: The bone mineral density revealed asymmetrical severe osteoporosis in the poliomyelitic limb. Given the risk of falls and fractures, she was commenced on oral bisphosphonate therapy. CONCLUSION: Poliomyelitis is an important acquired risk factor for regional osteoporosis. This condition should be detected and treated in this cohort of patients who are clearly at higher risk of fractures. PMID- 27252751 TI - Jaw tumor in primary hyperparathyroidism is not always a brown tumor. AB - Primary hyperparthyrodism (PHPT) is a common endocrine disease. It results from an inappropriate parathyroid hormone (PTH) secretion relative to serum ionized calcium level. Clinical manifestation of severe PHPT include bone disease called osteitis fibrosa cystica which reflects an increase osteoclastic resorption and osteoblastic activity. This high bone turnover is responsible of the occurrence of osteoclastomas, also named "brown tumors" (1). Rarely, PHPT may occur in inherited forms with association to fibrous jaw tumor that are unrelated to hyperparathyroidism. In this uncommon disease: hyperparathyroidism-jaw tumor (HPT JT) syndrome, parathyroid tumor is frequently malignant and usually associated with nonendocrine malignancies (2). We report a case of a HPT-JT syndrome to focus on the differential diagnosis with brown tumors. PMID- 27252752 TI - Efficacy of a specific rehabilitation protocol in postural control of a young woman with multiple fragility vertebral fractures: a case report. AB - The fragility vertebral fractures have a considerable impact on an individual's health-related quality of life due to pain, limitations in activity, social participation, altered mood and balance impairment. Physiotherapy interventions may have an important role in improving quality of life, balance and reducing the fracture risk in people with osteoporotic vertebral fractures. In literature there are only a few studies that examine exercise interventions in osteoporotic populations with vertebral fracture and few studies that examine the effects on balance with instrumental measurements. In this paper we present a case of a woman with fragility vertebral fractures and a related balance impairment and the effects of a specific rehabilitation program using both clinical evaluations that instrumental measurements. PMID- 27252753 TI - Effect of Fluoride, Casein Phosphopeptide-Amorphous Calcium Phosphate and Casein Phosphopeptide-Amorphous Calcium Phosphate Fluoride on Enamel Surface Microhardness After Microabrasion: An in Vitro Study. AB - OBJECTIVES: This study aimed to assess the effect of applying casein phosphopeptide- amorphous calcium phosphate (CPP-ACP) paste, casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) paste and sodium fluoride gel on surface microhardness of enamel after microabrasion. MATERIALS AND METHODS: Thirty freshly extracted human premolars were selected. All samples were subjected to hardness indentations made with the Vickers hardness machine and the average value was recorded as the initial surface microhardness. The specimens were then randomly divided into three groups (n=10) of CPP-ACPF, fluoride and CPPACP. The teeth were micro-abraded with Opalustre. Microhardness test was performed to assess the post-abrasion hardness. Three remineralization modalities were performed on samples of each group. The enamel surface microhardness measurements were performed. To compare the difference between groups, the rehardening and softening values were defined. One-way ANOVA and Tukey's post hoc test at a significance level of 5% were used for statistical analysis. RESULTS: The mean microhardness value (MMV) had a significant decrease after microabrasion from baseline. The MMV had a significant increase after remineralization in all groups. The MMV of CPP-ACPF group was significantly more than that of fluoride group (P=0.027). The rehardening value of fluoride group was significantly more than that of other groups (P<0.001). CONCLUSION: All the remineralizing agents were effective for rehardening the enamel after microabrasion. The CPP-ACP and CPP-ACPF pastes are effective, but to a lesser extent than neutral sodium fluoride gel in remineralizing enamel surface. Incorporation of fluoride to CPP-ACP formulation does not provide any additional remineralizing potential. PMID- 27252754 TI - Effect of Adhesive Application on Sealant Success: A Clinical Study of Fifth and Seventh Generation Adhesive Systems. AB - OBJECTIVES: The aim of the study was to compare the effect of fifth and seventh generation bonding agent on sealant success. MATERIALS AND METHODS: Sixty-four school children aged six to nine years received sealants in four permanent molars in a split mouth design, such that each patient received sealant in the first permanent molar with fifth generation bonding agent in one arch and seventh generation bonding agent in the other arch; contra-lateral molars were sealed with sealant alone. The evaluation was carried out at baseline, three months, six months and 12 months, according to the criteria by Feigal et al, in 2000. Chi- square test was used to analyze data at P<0.05 level of significance. RESULTS: Statistically significant differences were found for sealant retention between fifth generation and sealant group, and fifth generation and seventh generation groups; whereas, no significant difference was found for sealant retention between seventh generation and sealant group at three, six and 12 months. CONCLUSION: As separate etch and rinse steps are not required for seventh generation bonding agents, and almost similar results were obtained for both sealant and seventh generation groups, it can be concluded that application of sealant along with a seventh generation bonding agent may enhance sealant success and can be used for caries prevention in preventive programs. PMID- 27252755 TI - Effect of Different Obturation Materials on Residual Antimicrobial Activity of 2% Chlorhexidine in Dentin at Different Time Intervals: An Ex Vivo Study. AB - OBJECTIVES: The aim of this study was to evaluate the effect of gutta percha/AH26 and Resilon/RealSeal SE on residual antimicrobial activity of chlorhexidine (CHX) in human root dentin and suggest the best filling material when CHX is used as final irrigant. MATERIALS AND METHODS: One-hundred and forty-four single-rooted human teeth were selected for this study. Canals were instrumented to the apical size #35. Smear layer was removed using 5.25% NaOCl and 17% EDTA and then 108 teeth were irrigated with 2% CHX and randomly divided into three groups of gutta percha/AH26, Resilon/RealSeal SE and positive controls. Each group was divided into three subgroups for different time intervals (one, three and six weeks). Thirty-six teeth, as negative controls, were irrigated with saline and obturated with gutta percha/AH26 and Resilon/RealSeal SE. Dentin powder was prepared at the afore-mentioned intervals. After exposure to Enterococcus faecalis for 24 hours, colony forming units (CFUs) were counted and residual antimicrobial activity was calculated. The data were analyzed using the Kruskal Wallis test and one-way ANOVA. The significance level was set at P<0.05. RESULTS: The antimicrobial activity of CHX gradually decreased in a time-dependent manner but it maintained over 95% of its antimicrobial activity after six weeks. Moreover, Resilon/RealSeal SE significantly decreased the antimicrobial activity of CHX in comparison with gutta-percha/AH26 (P<0.05). CONCLUSION: After a final irrigation with CHX, gutta-percha/AH26 is a better choice for root canal obturation. PMID- 27252756 TI - Comparative Evaluation of Commercially Available Freeze Dried Powdered Probiotics on Mutans Streptococci Count: A Randomized, Double Blind, Clinical Study. AB - OBJECTIVES: Probiotic approaches are being considered to eliminate pathogenic microorganisms and are an alternative and promising way to combat infections by using harmless bacteria to displace pathogenic microorganisms. The aim of this study was to evaluate the effectiveness of commercially available freeze dried powdered probiotics on mutans streptococci count among 12-15 year-old Indian schoolchildren. MATERIALS AND METHODS: The study was conducted in two phases of in-vitro (phase I) and in-vivo (phase II) study, which was a double blind, randomized and placebo controlled clinical trial. A total of 33 schoolchildren between 12-15 years were included in the study. They were randomly allocated to three groups. Group A included 11 children using freeze dried Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum and Bifidobacterium lactis. Group B included 11 children using freeze dried lactic acid bacillus only. Group C included 11 children using placebo powder. The study was conducted over a period of three weeks and examination and sampling of the subjects were done on days 0 (baseline), seven, 14 and 21. RESULTS: For both the intervention groups A and B, statistically significant reduction (P<0.05) in salivary mutans streptococci counts was recorded up to the second week. CONCLUSION: Oral administration of probiotics showed a short-term effect on reduction of mutans streptococci count and showed a preventive role in caries development. PMID- 27252757 TI - Effects of Length and Inclination of Implants on Terminal Abutment Teeth and Implants in Mandibular CL1 Removable Partial Denture Assessed by Three Dimensional Finite Element Analysis. AB - OBJECTIVES: This study sought to assess the effects of length and inclination of implants on stress distribution in an implant and terminal abutment teeth in an implant assisted-removable partial denture (RPD) using three-dimensional (3D) finite element analysis (FEA). MATERIALS AND METHODS: In this in vitro study, a 3D finite element model of a partially dentate mandible with a distal extension RPD (DERPD) and dental implants was designed to analyze stress distribution in bone around terminal abutment teeth (first premolar) and implants with different lengths (7 and 10 mm) and angles (0 degrees , 10 degrees and 15 degrees ). RESULTS: Stress in the periodontal ligament (PDL) of the first premolar teeth ranged between 0.133 MPa in 10mm implants with 15 degrees angle and 0.248 MPa in 7mm implants with 0 degrees angle. The minimum stress was noted in implants with 10mm length with 0 degrees angle (19.33 MPa) while maximum stress (25.78 MPa) was found in implants with 10mm length and 15 degrees angle. In implants with 7 mm length, with an increase in implant angle, the stress on implants gradually increased. In implants with 10 mm length, increasing the implant angle gradually increased the stress on implants. CONCLUSION: Not only the length of implant but also the angle of implantation are important to minimize stress on implants. The results showed that vertical implant placement results in lower stress on implants and by increasing the angle, distribution of stress gradually increases. PMID- 27252758 TI - Effect of Saliva Contamination on Microleakage Beneath Bonded Brackets: A Comparison Between Two Moisture-Tolerant Bonding Systems. AB - OBJECTIVES: This study aimed to evaluate the effects of saliva contamination on the metallic bracket microleakage bonded with two moisture-tolerant bonding systems. MATERIALS AND METHODS: Ninety freshly extracted premolar teeth were randomly divided into six groups of 15 with the following treatments: G1 (control): After acid etching, Assure primer and Assure adhesive were applied to non-contaminated enamel surfaces. G2 (contaminated after etching): The etched enamel surface was exposed to saliva, then Assure primer and Assure adhesive were applied. G3 (contaminated after priming): Saliva contamination was done after application of Assure primer. The exact same procedures were applied to groups G4 to G6 except that TIMP primer and Transbond Plus adhesive system were used. To measure the microleakage score, the teeth were stained with 2% methylene blue for 24 hours, sectioned and examined under a stereomicroscope at *16 magnification. Data analysis was performed using Fisher's exact test. RESULTS: In dry conditions, Assure and TMIP were not significantly different in terms of microleakage scores. All contaminated groups exhibited higher microleakage score at the enamel/adhesive interface compared to the bracket/adhesive interface (P< 0.01). In wet conditions, Assure groups showed higher microleakage at the enamel adhesive interface compared to the TMIP groups (P<0.05). At the bracket-adhesive interface, the microleakage scores were not significantly different in saliva contaminated groups compared to the controls. CONCLUSION: Saliva contamination caused greater microleakage at the enamel-adhesive interface compared to the adhesive-bracket interface. PMID- 27252759 TI - Relationship of the Gonial Angle and Inferior Alveolar Canal Course Using Cone Beam Computed Tomography. AB - OBJECTIVES: Accurate localization of the inferior alveolar canal (IAC) is extremely important in some dental treatments. Anatomical variation of the canal means that it can be difficult to locate. The purpose of this study was to assess the relationship of the gonial angle (GA) size and IAC position using cone beam computed tomography (CBCT). MATERIALS AND METHODS: In this in vitro study, 61 dry adult human hemi-mandibles were used. The CBCT scans were taken of all samples and GA was measured on all CBCT scans. The samples were divided into two groups of low angle (<=125 degrees ) and high angle (>125 degrees ). The canal dimensions, length and course were evaluated. On the sagittal view, the IAC path was classified as type A, B or C. On the axial view, canal course was defined as A1 or A2 according to the mental foramen angle. RESULTS: The average GA size was 121.8+/-7.05 degrees at the right side and 123.8+/-6.32 degrees at the left side. On the sagittal view, there was a significant correlation between the GA size and the canal course (P=0.04). In the high-angle group, type A was dominant; whereas in the low-angle group, type B was more common. On the axial view of IAC course, type A1 was more common (73.43%). CONCLUSION: The results showed that GA size was associated with IAC course. In cases with a larger GA, the canal runs in a more straightforward path, and at the same level as the mental foramen. PMID- 27252760 TI - Treatment of Intrabony Defects by DFDBA Alone or in Combination with PRP: A Split Mouth Randomized Clinical and Three-Dimensional Radiographic Trial. AB - OBJECTIVES: The efficacy of adding platelet-rich plasma (PRP) to demineralized freeze-dried bone allograft (DFDBA) in order to improve the clinical and radiographic results obtained in treatment of deep periodontal intrabony defects has yet to be fully elucidated. MATERIALS AND METHODS: This double blind, split mouth randomized controlled clinical trial was conducted on 12 patients with two comparable bilateral intrabony defects. Each pair of defects was randomly treated with DFDBA+PRP (test) or DFDBA alone (control). Clinical attachment level (CAL), intrabony defect depth (IDD), distance from the stent to the alveolar crest and pocket depth (PD) as well as radiographic parameters including the radiographic defect depth, width and angulation were measured at baseline and six months post operatively. The paired t-test was used to compare the pre and post-treatment values and the unpaired t-test compared the test and control groups. RESULTS: The mean reductions in PD and CAL were 4.5 +/-1.3 mm and 3.6+/-1.6 mm in sites treated with DFDBA+ PRP, respectively (P<0.01); these reductions were 4.1+/-1.4 mm and 3.5+/-1.3 mm, respectively in DFDBA group (P<0.01). Radiographic evaluation revealed 2.5+/-1.1 mm reduction in the radiographic defect depth in the test and 2.1+/-1.2 mm in the control sites. The defect angulation increased at both sites. Statistically, there were no significant differences between the two treatment modalities (P<0.01). CONCLUSION: This study showed that both treatments resulted in significant PD reduction, CAL gain and IDD reduction. Also, PRP failed to enhance the results obtained by DFDBA. PMID- 27252761 TI - Accuracy of Implant Position Transfer and Surface Detail Reproduction with Different Impression Materials and Techniques. AB - OBJECTIVES: The purpose of this study was to compare the accuracy of implant position transfer and surface detail reproduction using two impression techniques and materials. MATERIALS AND METHODS: A metal model with two implants and three grooves of 0.25, 0.50 and 0.75 mm in depth on the flat superior surface of a die was fabricated. Ten regular-body polyether (PE) and 10 regular-body polyvinyl siloxane (PVS) impressions with square and conical transfer copings using open tray and closed tray techniques were made for each group. Impressions were poured with type IV stone, and linear and angular displacements of the replica heads were evaluated using a coordinate measuring machine (CMM). Also, accurate reproduction of the grooves was evaluated by a video measuring machine (VMM). These measurements were compared with the measurements calculated on the reference model that served as control, and the data were analyzed with two-way ANOVA and t-test at P= 0.05. RESULTS: There was less linear displacement for PVS and less angular displacement for PE in closed-tray technique, and less linear displacement for PE in open tray technique (P<0.001). Also, the open tray technique showed less angular displacement with the use of PVS impression material. Detail reproduction accuracy was the same in all the groups (P>0.05). CONCLUSION: The open tray technique was more accurate using PE, and also both closed tray and open tray techniques had acceptable results with the use of PVS. The choice of impression material and technique made no significant difference in surface detail reproduction. PMID- 27252762 TI - A Case of Successful Retreatment of a Maxillary Lateral Incisor with a Supernumerary Root. AB - Knowledge about the morphology of the root canal system is a pre-requisite for achieving a successful outcome in root canal treatment. In this report, a patient with a maxillary lateral incisor which had previously undergone orthograde endodontic retreatment for two times is discussed. The tooth had been misdiagnosed with a palatal groove or a root fracture, its prognosis had been determined to be poor and extraction was advised by a practitioner. During our evaluation, an unrecognized supernumerary root and root canal were detected and the tooth was maintained successfully with orthograde endodontic retreatment. The use of cone beam computed tomography (CBCT) and magnification were of significance in the treatment process of this case. PMID- 27252763 TI - The Role of Lead Exposure on Attention-Deficit/ Hyperactivity Disorder in Children: A Systematic Review. AB - OBJECTIVE: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common behavioral disorders in children effecting the families and society. This systematic review examined the literature on the role of lead exposure in children with ADHD? ?symptoms. Articles were analytically compared, focusing on the methodology used to assess exposure and? ?adverse effects? ?on children with ADHD. METHOD: Using the search strategy from six databases (Pub Med, PsycINFO, Web of Science, SID, IRAN Medex, IRAN DOC), hand searching in key journals, list of references of selected articles and gray literature, without time and language limitation, articles up to May 2014 were entered into this review. In this review, 1,387 articles were acquired at the primary search. Study selection and quality assessment processes were done based on Cochrane library guidelines. After assessing the quality and inclusion and exclusion criteria, 18 articles were selected and entered into the data synthesis. RESULTS: Blood Lead level (BLL) of less than 10ug/dL in children has been attributed to at least one type of ADHD i.e., Combined / Inattentive / Hyperactive-Impulsive. The results of this study revealed that in 16 out of the 18 studies, a significant association was found between BLL and one of the types of ADHD. CONCLUSION: Based on the findings of this study, even the BLL of less than the action level of 10ug/dL, chosen by Centers for Disease Control and Prevention (CDC), may affect children with ADHD.. PMID- 27252764 TI - Transition to Psychosis: Evaluation of the First-Degree Relatives of Patients with Schizophrenia . AB - OBJECTIVE: Schizophrenia and other psychoses have devastating personal and social impacts and many efforts have been devoted to study prodromal syndromes for psychosis in order to achieve earlier detection and interventions. However, only few studies have been performed in developing countries on this subject, and there is a dearth of evidence in the Iranian population. In this study, we focused on conversion rate to psychosis and changes in prodromal symptoms in a group of first-degree relatives of patients with schizophrenia and to compare the conversion rate in those with and without prodromal symptoms as assessed by the Structured Interview for Prodromal Syndromes (SIPS) and Scale of Prodromal Symptoms (SOPS). METHOD: Participants were the first-degree relatives of hospitalized patients with schizophrenia at Roozbeh Hospital, Tehran, Iran. At baseline, a trained psychiatrist interviewed the participants using the SIPS and the SOPS and assigned them to high- or low-risk groups either based on the presence of prodromal criteria or seeking mental health services. After 12 months, the same examiner re-evaluated the participants in order to determine the changes in their symptoms and identify the probable transitions to psychosis. RESULTS: One hundred participants, 50 participants within each of high- or low risk groups, were recruited at baseline. Eight participants dropped out of the study. At the follow-up, the rate of transition to full psychosis among high-risk group was 13% (95% CI [0.029, 0.23]), whereas none of the low-risk participants developed psychosis. None of the high-risk participants demonstrated attenuation in their prodromal states after a one-year follow-up. In contrast, of the 50 low risk participants, three experienced prodromal symptoms for psychosis during this period. High-risk participant's illustrated higher severity in almost all of the SOPS items compared to the low-risk participants at both baseline and follow-up evaluations. CONCLUSION: Prodromal syndrome for psychosis based on the SIPS and the SOPS was a predictive factor for transition to psychosis after a 12-month period in a group of first-degree relatives of patients with schizophrenia admitted to a psychiatric hospital in Iran. Conducting further studies on this at risk population is highly recommended in order to provide practical methods for early screening and therapeutic interventions.. PMID- 27252765 TI - Investigation of Mental Health in Patients with Medically Unexplained Physical Symptoms. AB - OBJECTIVE: Medically unexplained symptoms are physical symptoms, which cannot be explained by organic causes. This study aimed to investigate mental health in patients with medically unexplained physical symptoms. METHOD: One hundred outpatients who were admitted to the Electro Diagnosis Clinic of Imam Khomeini hospital, Ahvaz/Iran, participated in this study. Data were collected using physical examination, paraclinical examinations, and SCL-90-R, and analyzed through multivariate analysis of variance (MANOVA), Chi-square test and Fisher's exact test. RESULTS: The findings revealed significant differences between clients with medically explained and unexplained symptoms in obsessive compulsive and somatization (p<0.05). Differences in depression, anxiety, phobia, psychosis, aggression and paranoia were not significant (p>0.05). CONCLUSION: The present study suggested an association between some psychological problems and somatic symptoms. Therefore, screening for psychological impairments can improve clinical outcomes.. PMID- 27252766 TI - Effectiveness of Group Cognitive-Behavioral Therapy on Symptoms of Premenstrual Syndrome (PMS) . AB - OBJECTIVE: Standards of care and treatment of premenstrual syndrome (PMS) vary. Non-drug psychosocial intervention therapy is recommended for women with any kind of discomfort or distress caused by PMS. The current study examined the effectiveness of group cognitive-behavioral therapy on the symptoms of PMS at a girls' dormitory of North Khorasan University of Medical Sciences. METHOD: In this quasi-experimental study, 32 female students with PMS who were majoring in nursing and midwifery and residing in the dormitory were selected using the convenience sampling method and were assigned to experimental and control groups. The Standardized Premenstrual Symptoms Screening Tool was used as the research tool. Eight sessions of cognitive-behavioral group therapy were held for the students Results: There was a significant difference in psychological symptoms before and after cognitive-behavioral therapy (p=0.012). Furthermore, cognitive behavioral therapy was effective on social interferences caused by PMS symptoms (p=0.012). CONCLUSION: Group cognitive-behavioral therapy effectively alleviates PMS symptoms in female college students.. PMID- 27252767 TI - Iranian Version of Manchester Driving Behavior Questionnaire (MDBQ): Psychometric Properties. AB - OBJECTIVE: Since the study of driving behavior is of great importance, we conducted this research to investigate the psychometric properties and the factorial structure of the Manchester Driver Behavior Questionnaire (DBQ) in Iranian drivers. METHOD: This cross - sectional research was performed on a sample of 800 drivers (of category D and C) aged 23- 75 who were referred to Imam Sajjad Centre for drug Addiction Diagnosis. Manchester Driver Behavior Questionnaire (DBQ), a demographic questionnaire, were conducted to the sample. To analyze data, we used factor analysis, internal consistency (Cronbach's'alpha), split half, and test-retest using SPSS18 Software. RESULTS: As a result of reliability analysis and exploratory factor analysis by principal component and Varimax rotation, we extracted six factors (willful violations, unintentional errors, advertent errors, deliberate mistakes, unintentional violation, and unintentional mistakes, respectively). The factors reliability ranged from 0.65 to 0.75. The test-retest correlations of the DBQ and split- half reliability were 0.56 and 0.77, respectively. CONCLUSION: The results revealed that the Persian version of the DBQ in category D and C drivers is a valid and reliable tool to assess driving behaviors in Iranian drivers.. PMID- 27252768 TI - The Association between Dairy Intake, Simple Sugars and Body Mass Index with Expression and Extent of Anger in Female Students . AB - OBJECTIVE: A significant increase in violence in the world and its impact on public health and society can be an important reason to offer solutions to reduce or control anger. Studies have shown that specific food groups may be effective in controlling mental disorders such as depression, anxiety and anger. The purpose of this study was to determine the relationship between food intake and Body Mass Index on state-trait anger expression in female students of Shahid Beheshti University of Medical Sciences. METHOD: In this cross-sectional study, 114 female students were randomly selected from dormitories of Shahid Beheshti University of Medical Sciences. Body height and weight were measured using the scale and stadiometer, respectively. The required data for evaluating the relationship between state-trait anger expression and food consumption groups were collected using State-Trait Anger Expression Inventory-2 (STAXI-2) and Food Frequency questionnaires. RESULTS: The results revealed a significant negative correlation between consumption of dairy product and trait anger (angry reaction), (P = 0.015). This association remained significant after adjustment of confounding factors. No significant correlations were found between other food groups as well as BMI and state-trait anger expression. CONCLUSION: The higher intake of dairy products reduced state-trait anger expression. This result is consistent with the findings of many studies on the effect of dairy consumption on mental disorders. Therefore, consumption of dairy products can be a solution for reducing anger.. PMID- 27252769 TI - Late Recovery from Stuttering: The Role of Hand Dominancy, Fine Motor and Inhibition Control. AB - OBJECTIVE: There are controversial reports about factors that affect recovery from stuttering. In the present study, the effect of hand dominancy, fine motor and inhibition control on late recovery from stuttering was investigated among a group of Kurdish-Persian children who stuttered in Iran. METHOD: Twenty-two Kurdish-Persian children aged 7-14 years who stuttered were followed for 6 years. Based on the evaluation of three experienced speech therapists and parental judgments, these children were classified into recovered or persistent groups. Data about fine motor control of hand and inhibition control were obtained, using Purdue Pegboard and Victoria Strop Color Word Tests, respectively. Risk factors including sex, age, and family history of stuttering, handedness, inhibitory control and fine motor control of hand were compared between the groups and modeled to predict recovery from stuttering using logistic regression. RESULTS: From the 22 participants, 5 (22.7%) recovered from stuttering. The recovered and persistent groups did not show significant differences in the interference effect. By dividing the scores of the Purdue Pegboard tests to the right and left hand, we created a new Handedness Index (HI). HI was significantly higher in the recovered group. The score of right hand was higher than the left in the recovered group, but no difference was found between the two hands in the persistent group. Among the investigated risk factors, only HI could predict the recovery from or persistency of stuttering with 94% sensitivity and 84% specificity. CONCLUSION: Handedness Index can predict the recovery from stuttering significantly among children who stutter.. PMID- 27252770 TI - Evaluating Autonomic Parameters: The Role of Sleep Duration in Emotional Responses to Music . AB - OBJECTIVE: It has been recognized that sleep has an important effect on emotion processing. The aim of this study was to investigate the effect of previous night sleep duration on autonomic responses to musical stimuli in different emotional contexts. METHOD: A frequency based measure of GSR, PR and ECG signals were examined in 35 healthy students in three groups of oversleeping, lack of sleep and normal sleep. RESULTS: The results of this study revealed that regardless of the emotional context of the musical stimuli (happy, relax, fear, and sadness), there was an increase in the maximum power of GSR, ECG and PR during the music time compared to the rest time in all the three groups. In addition, the higher value of these measures was achieved while the participants listened to relaxing music. Statistical analysis of the extracted features between each pair of emotional states revealed that the most significant differences were attained for ECG signals. These differences were more obvious in the participants with normal sleeping (p<10-18). The higher value of the indices has been shown, comparing long sleep duration with the normal one. CONCLUSION: There was a strong relation between emotion and sleep duration, and this association can be observed by means of the ECG signals.. PMID- 27252771 TI - Escitalopram in Preschool-Age Children Diagnosed with Obsessive Compulsive Disorder: A Case Report . PMID- 27252772 TI - Identification of donor splice sites using support vector machine: a computational approach based on positional, compositional and dependency features. AB - BACKGROUND: Identification of splice sites is essential for annotation of genes. Though existing approaches have achieved an acceptable level of accuracy, still there is a need for further improvement. Besides, most of the approaches are species-specific and hence it is required to develop approaches compatible across species. RESULTS: Each splice site sequence was transformed into a numeric vector of length 49, out of which four were positional, four were dependency and 41 were compositional features. Using the transformed vectors as input, prediction was made through support vector machine. Using balanced training set, the proposed approach achieved area under ROC curve (AUC-ROC) of 96.05, 96.96, 96.95, 96.24 % and area under PR curve (AUC-PR) of 97.64, 97.89, 97.91, 97.90 %, while tested on human, cattle, fish and worm datasets respectively. On the other hand, AUC-ROC of 97.21, 97.45, 97.41, 98.06 % and AUC-PR of 93.24, 93.34, 93.38, 92.29 % were obtained, while imbalanced training datasets were used. The proposed approach was found comparable with state-of-art splice site prediction approaches, while compared using the bench mark NN269 dataset and other datasets. CONCLUSIONS: The proposed approach achieved consistent accuracy across different species as well as found comparable with the existing approaches. Thus, we believe that the proposed approach can be used as a complementary method to the existing methods for the prediction of splice sites. A web server named as 'HSplice' has also been developed based on the proposed approach for easy prediction of 5' splice sites by the users and is freely available at http://cabgrid.res.in:8080/HSplice. PMID- 27252773 TI - Efficacy of extra-peritoneal pelvic packing in hemodynamically unstable pelvic fractures, a Propensity Score Analysis. AB - BACKGROUND: An option for emergency control of pelvic hemorrhage is Extra peritoneal Pelvic Packing (EPP), which addresses the retroperitoneal source of exsanguination in pelvic fractures. The aim of this study was to demonstrate the efficacy of early EPP in reducing mortality due to hemorrhage from pelvic fractures, and to evaluate the impact of packing on transfusion requirements within the first 24 h and ICU length of stay (ICU-LOS). All data pertaining trauma patients admitted from October 2002 and December 2103 with hemodynamic instability and pelvic fractures were selected from the Hospital Trauma Registry. Patients with severe brain injury and bleeding from extra-pelvic sources were excluded. Patient population was divided into two groups: EPP group, including patients admitted from 2009 to 2013, with EPP as part of the treatment algorithm, and NO-EPP group, from 2002 to 2008, without EPP as atherapeutic option. Descriptive statistical analysis was performed on allpatients. Twenty-five patients of each group with similar features were matched using Propensity Score Analysis (PSA). RESULTS: Six hundred eighty out of 4659 major trauma (14.6 %) presented a pelvic fracture. In 78 hemodynamically unstable patients (30 in EPP group,48 in NO-EPP group) the major source of bleeding was the pelvis. Among patients selected by PSA early mortality was significantly reduced in EPP group (20 vs 52 %, p = .03) compared to NO-EPP, notwithstanding similar hemodynamic impairment. No difference was observed in transfusion requirements and ICU-LOS. CONCLUSIONS: The EPP is a safe and quick procedure, able to improve hemodynamic stabilization and to reduce acute mortality due to hemorrhage in patients with pelvic fracture, in combination with optimized transfusion protocol. EPP may be useful as a bridge for time-consuming procedures, such as angio-embolization. PMID- 27252775 TI - Syrian refugees in Lebanon: the search for universal health coverage. AB - The crisis in Syria has forced more than 4 million people to find refuge outside Syria. In Lebanon, in 2015, the refugee population represented 30 % of the total population. International health assistance has been provided to refugee populations in Lebanon. However, the current humanitarian system has also contributed to increase fragmentation of the Lebanese health system. Ensuring universal health coverage to vulnerable Lebanese, Syrian and Palestinian refugees will require in Lebanon to redistribute the key functions and responsibilities of the Ministry of Health and its partners to generate more coherence and efficiency. PMID- 27252774 TI - Gastrodia and Uncaria (tianma gouteng) water extract exerts antioxidative and antiapoptotic effects against cerebral ischemia in vitro and in vivo. AB - BACKGROUND: Gastrodia and Uncaria decoction (tianma gouteng yin) is commonly used in Chinese medicine to treat cerebral ischemia. The aim of this study was to investigate the neuroprotective effects of a water extract (GUW) of Gastrodia elata (tianma; GE) and Uncaria rhynchophylla (gouteng; UR) against ischemic insult using oxygen-glucose-deprived neuronal differentiated PC12 cells and rats subjected to middle cerebral artery occlusion (MCAO). METHODS: GUW was prepared by boiling raw GE and UR in water, followed by the lyophilization of the resulting extract. Neuronal differentiated PC12 cells were subjected to oxygen glucose deprivation with or without GUW. The neuroprotective effects of GUW were compared with those of the corresponding GE and UR extracts to tease apart the effects of the different herbs. The synergistic effect of GE and UR in GUW was measured using a modified version of Burgi's formulae. The neuroprotective mechanisms via Nrf2 and anti-apoptotic pathways were investigated using real time PCR and enzyme activity assays. The neuroprotective effects of GUW were studied in vivo using a rat MCAO model. Neurofunctional outcome and brain infarct volume we assessed. H&E staining, cresyl violet staining and immunohistochemistry were performed to assess the histological outcome. RESULTS: The results of lactate dehydrogenase assay showed that GUW protected cells in a concentration-dependent manner (P < 0.001). Moreover, the neuroprotective effects of GUW were greater than those of GE + UR (P = 0.018). Burgi's formula showed that the herbs in GUW acted synergistically to protect cells from ischemic injury. GUW significantly upregulated Bcl-2 expression (P = 0.0130) and reduced caspase-3 activity by 60 % (P < 0.001). GUW upregulated Nrf-2 expression (P = 0.0066) and the antioxidant response element pathway genes. The infarct volume was reduced by 55 % at day 7 of reperfusion (P < 0.001), and significant improvements were observed in the neurological deficit score and beam-walking test at 7 days (P < 0.001). H&E and cresyl violet staining revealed higher tissue integrity in the GUW treatment group compared with MCAO rats. CONCLUSION: GUW modulated the antioxidant system and antiapoptotic genes in oxygen-glucose deprived neuronal differentiated PC12 cells and MCAO sprague-dawley rats. PMID- 27252776 TI - Natural curcuminoids encapsulated in layered double hydroxides: a novel antimicrobial nanohybrid. AB - Currently, there is an increased scientific interest to discover plant based drug formulations with improved therapeutic potential. Among the cornucopia of traditional medicinal plants, Curcuma longa rhizomes have been used as a powerful antibacterial and antifungal agent. However, its practical applications are limited due to its instability under thermal and UV radiation and its low bioavailability and the extensive procedures needed for isolation. This study focuses on exploring the potential of nanotechnology-based approaches to stabilize the natural curcuminoids, the major active components in turmeric without the need for its isolation, and to evaluate the release characteristics, stability and antimicrobial activity of the resulting nanohybrids. Natural curcuminoids were selectively encapsulated into nanolayers present in Mg-Al layered double hydroxides (LDHs) using a method that avoids any isolation of the curcuminoids. The products were characterized using solid state techniques, while thermal and photo-stability were studied using thermogravimetric analysis (TGA) and UV exposure data. The morphological features were studied using scanning electron microscope (SEM) and transmission electron microscope (TEM). Drug release characteristics of the nanohybrid were quantitatively monitored under pH 3 and 5, and therapeutic potentials were assessed by using distinctive kinetic models. Finally, the antimicrobial activity of curcuminoids-LDH was tested against three bacterial and two fungal species. Powder X-ray diffraction, Fourier transform infra-red spectroscopy, SEM and TEM data confirmed the successful and selective encapsulation of curcuminoids in the LDH, while the TGA and UV exposure data suggested the stabilization of curcuminoids within the LDH matrix. The LDH demonstrated a slow and a sustained release of the curcuminoids in an acidic medium, while it was active against the three bacteria and two fungal species used in this study, suggesting its potential applications in pharmaceutical industry.Graphical abstractSynthesis of Curcuminoid-LDH by coprecipitation method and the slow release process of curcuminoids from LDH matrix. PMID- 27252777 TI - Kinetic, isotherm and thermodynamic studies on biosorption of chromium(VI) by using activated carbon from leaves of Ficus nitida. AB - BACKGROUND: Kinetics, thermodynamics and equilibrium of the removal of chromium(VI) ions from aqueous solutions by using chemically activated leaves of Ficus nitida were investigated. Adsorption runs were performed as a function of pH, mass of biosorbent, contact time, initial concentration of chromium(VI) ions and temperature. RESULTS: The optimum conditions for maximum removal of chromium(VI) ion from aqueous solutions (about 99 %) were found to be 0.80 g of chemically activated leaves of F. nitida, 25 min, 50.0 mg/L of initial concentration of chromium(VI). Values of thermodynamic activation parameters proved that the biosorption process is spontaneous and endothermic. Results were analyzed by using Langmuir, Freundlich and Temkin models. CONCLUSIONS: Results of the study showed that the chemically activated leaves of F. nitida can be used as low cost, ecofriendly and effective sorbent for the removal of chromium(VI) from aqueous solutions.Graphical abstractFicus nitida is an efficient bio-sorbent used for removal of Cr(VI) ion. PMID- 27252778 TI - Problem Management Plus (PM+) in the treatment of common mental disorders in women affected by gender-based violence and urban adversity in Kenya; study protocol for a randomized controlled trial. AB - BACKGROUND: Women affected by adversity, including gender-based violence, are at increased risk for developing common mental disorders such as depression, anxiety and posttraumatic stress disorder (PTSD). The World Health Organization (WHO) has developed Problem Management Plus (PM+), a 5-session, individual psychological intervention program, that can be delivered by non-specialist counsellors that addresses common mental disorders in people affected by adversity. The objectives of this study are to evaluate effectiveness of PM+ among women who have been affected by adversity, including gender-based violence, and to perform a process evaluation. METHODS: Informed by community consultations, the PM+ manual has been translated and adapted to the local context. A randomized controlled trial will be carried out in the catchment areas of three local health care facilities in Dagoretti Sub County, Nairobi. After informed consent, females with high psychological distress (General Health Questionnaire-12 (score >2) and functional impairment (WHO Disability Assessment Schedule 2.0 score >16) will be randomised to PM+ (n = 247) or enhanced treatment as usual (n = 247). Post-treatment and 3 months post-treatment follow-up assessments include psychological distress, functional disability, PTSD symptoms, perceived problems for which the person seeks help, health care use and health costs. For evaluating the process of implementing PM+ within local communities in Nairobi 20 key informant interviews will be carried out in participants, PM+ providers, decision makers, clinical staff. DISCUSSION: If PM+ is proven effective, it will be rolled out to other low and middle income areas and other populations for further adaptation and testing. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616000032459. Registered prospectively on January 18, 2016. PMID- 27252779 TI - DNA microarray of global transcription factor mutant reveals membrane-related proteins involved in n-butanol tolerance in Escherichia coli. AB - BACKGROUND: Escherichia coli has been explored as a platform host strain for biofuels production such as butanol. However, the severe toxicity of butanol is considered to be one major limitation for butanol production from E. coli. The goal of this study is therefore to construct butanol-tolerant E. coli strains and clarify the tolerance mechanisms. RESULTS: A recombinant E. coli strain harboring sigma(70) mutation capable of tolerating 2 % (v/v) butanol was isolated by the global transcription machinery engineering (gTME) approach. DNA microarrays were employed to assess the transcriptome profile of butanol-tolerant strain B8. Compared with the wild-type strain, 329 differentially expressed genes (197 up regulated and 132 down-regulated) (p < 0.05; FC >= 2) were identified. These genes are involved in carbohydrate metabolism, energy metabolism, two-component signal transduction system, oxidative stress response, lipid and cell envelope biogenesis and efflux pump. CONCLUSIONS: Several membrane-related proteins were proved to be involved in butanol tolerance of E. coli. Two down-regulated genes, yibT and yghW, were identified to be capable of affecting butanol tolerance by regulating membrane fatty acid composition. Another down-regulated gene ybjC encodes a predicted inner membrane protein. In addition, a number of up-regulated genes, such as gcl and glcF, contribute to supplement metabolic intermediates for glyoxylate and TCA cycles to enhance energy supply. Our results could serve as a practical strategy for the construction of platform E. coli strains as biofuel producer. PMID- 27252780 TI - A novel and simple approach to the good process performance of methane recovery from lignocellulosic biomass alone. AB - BACKGROUND: Solid-state anaerobic digestion (SS-AD) has been increasingly used for lignocellulosic biomass treatment. However, the separate reactor required for pretreatment prior digestion, poor treatment capacity, and process stability inhibit further development of the SS-AD. In this study, a novel method called SS AD with simultaneous urea treatment and soil addition was proposed. The process performance of methane yield from rape straw was investigated by adopting the method. RESULTS: The results show that the process performance of methane yield from rape straw using the method was better. The level of daily methane yield and the process stability were improved. The time required for reaching steady state was 6 days shorter than that of the common method (SS-AD and urea pretreatment), and the methane content in a stable-state level was 77.5-80.1 %. The total methane yield [409.6 L/kg volatile solids (VS)] was the maximal after using the method, which was 22.6 and 76.8 % higher than those of SS-AD with urea pretreatment and SS-AD with simultaneous urea treatment, respectively. In addition, the carbon dioxide content was reduced significantly. Degradation of feedstock was high; the highest reductions of VS, cellulose, and hemicellulose were 57.1, 61.4, and 65.8 %, respectively, which were in accordance with the maximal methane yield. SEM images also indicate that the biodegradation degree of rape straw in SS-AD was in line with methane yield. CONCLUSIONS: The process performance of SS-AD of lignocellulosic biomass (rape straw) with simultaneous urea treatment and soil addition was better. This simplified, low cost, and efficient method has good practicability, which can try to be used for other types of lignocellulosic biomass. PMID- 27252781 TI - A marker chromosome in post-transplant bone marrow. AB - Detection of small supernumerary marker chromosomes in karyotype analysis represents a diagnostic challenge. While such markers are usually detected during cytogenetic studies of constitutional chromosome abnormalities, they have also been found in specimens submitted from patients with acquired malignancies. We report here the detection of a marker chromosome in a bone marrow specimen from a patient who received a bone marrow transplantation. We discuss the importance of proper characterization and interpretation of marker chromosomes in clinical practice. PMID- 27252783 TI - Changes of 5-hydroxymethylcytosine distribution during myeloid and lymphoid differentiation of CD34+ cells. AB - BACKGROUND: Hematopoietic stem cell renewal and differentiation are regulated through epigenetic processes. The conversion of 5-methylcytosine into 5 hydroxymethylcytosine (5hmC) by ten-eleven-translocation enzymes provides new insights into the epigenetic regulation of gene expression during development. Here, we studied the potential gene regulatory role of 5hmC during human hematopoiesis. RESULTS: We used reduced representation of 5-hydroxymethylcytosine profiling (RRHP) to characterize 5hmC distribution in CD34+ cells, CD4+ T cells, CD19+ B cells, CD14+ monocytes and granulocytes. In all analyzed blood cell types, the presence of 5hmC at gene bodies correlates positively with gene expression, and highest 5hmC levels are found around transcription start sites of highly expressed genes. In CD34+ cells, 5hmC primes for the expression of genes regulating myeloid and lymphoid lineage commitment. Throughout blood cell differentiation, intragenic 5hmC is maintained at genes that are highly expressed and required for acquisition of the mature blood cell phenotype. Moreover, in CD34+ cells, the presence of 5hmC at enhancers associates with increased binding of RUNX1 and FLI1, transcription factors essential for hematopoiesis. CONCLUSIONS: Our study provides a comprehensive genome-wide overview of 5hmC distribution in human hematopoietic cells and new insights into the epigenetic regulation of gene expression during human hematopoiesis. PMID- 27252782 TI - Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres. AB - BACKGROUND: Chromatin containing the histone variant CENP-A (CEN chromatin) exists as an essential domain at every centromere and heritably marks the location of kinetochore assembly. The size of the CEN chromatin domain on alpha satellite DNA in humans has been shown to vary according to underlying array size. However, the average amount of CENP-A reported at human centromeres is largely consistent, implying the genomic extent of CENP-A chromatin domains more likely reflects variations in the number of CENP-A subdomains and/or the density of CENP-A nucleosomes within individual subdomains. Defining the organizational and spatial properties of CEN chromatin would provide insight into centromere inheritance via CENP-A loading in G1 and the dynamics of its distribution between mother and daughter strands during replication. RESULTS: Using a multi-color protein strategy to detect distinct pools of CENP-A over several cell cycles, we show that nascent CENP-A is equally distributed to sister centromeres. CENP-A distribution is independent of previous or subsequent cell cycles in that centromeres showing disproportionately distributed CENP-A in one cycle can equally divide CENP-A nucleosomes in the next cycle. Furthermore, we show using extended chromatin fibers that maintenance of the CENP-A chromatin domain is achieved by a cycle-specific oscillating pattern of new CENP-A nucleosomes next to existing CENP-A nucleosomes over multiple cell cycles. Finally, we demonstrate that the size of the CENP-A domain does not change throughout the cell cycle and is spatially fixed to a similar location within a given alpha satellite DNA array. CONCLUSIONS: We demonstrate that most human chromosomes share similar patterns of CENP-A loading and distribution and that centromere inheritance is achieved through specific placement of new CENP-A near existing CENP-A as assembly occurs each cell cycle. The loading pattern fixes the location and size of the CENP-A domain on individual chromosomes. These results suggest that spatial and temporal dynamics of CENP-A are important for maintaining centromere identity and genome stability. PMID- 27252784 TI - Abnormal X chromosome inactivation and sex-specific gene dysregulation after ablation of FBXL10. AB - BACKGROUND: Almost all CpG-rich promoters in the mammalian genome are bound by the multidomain FBXL10 protein (also known as KDM2B, JHDM1B, CXXC2, and NDY1). FBXL10 is expressed as two isoforms: FBXL10-1, a longer form that contains an N terminal histone demethylase domain with C-terminal F-box, CXXC, PHD, RING, and leucine-rich repeat domains, and FBXL10-2, a shorter form that initiates at an alternative internal exon and which lacks the histone demethylase domain but retains all other annotated domains. Selective deletion of Fbxl10-1 had been reported to produce a low penetrance and variable phenotype; most of the mutant animals were essentially normal. We constructed mutant mouse strains that were either null for Fbxl10-2 but wild type for Fbxl10-1 or null for both Fbxl10-1 and Fbxl10-2. RESULTS: Deletion of Fbxl10-2 (in a manner that does not perturb expression of Fbxl10-1) produced a phenotype very different from the Fbxl10-1 mutant, with craniofacial abnormalities, neural tube defects, and increased lethality, especially in females. Mutants that lacked both FBXL10-1 and FBXL10-2 showed embryonic lethality and even more extreme sexual dimorphism, with more severe gene dysregulation in mutant female embryos. X-linked genes were most severely dysregulated, and there was marked overexpression of Xist in mutant females although genes that encode factors that bind to Xist RNA were globally downregulated in mutant female as compared to male embryos. CONCLUSIONS: FBXL10 is the first factor shown to be required both for the normal expression and function of the Xist gene and for normal expression of proteins that associate with Xist RNA; it is proposed that FBXL10 coordinates the expression of Xist RNA with proteins that associate with this RNA. The function of FBXL10 is largely independent of the histone demethylase activity of the long form of the protein. PMID- 27252785 TI - Serotype epidemiology and multidrug resistance patterns of Salmonella enterica infecting humans in Italy. AB - BACKGROUND: Salmonella enterica is the zoonotic agent most frequently responsible for foodborne infections in humans worldwide. In this work the presence of S. enterica was investigated in 734 unique enteropathogenic isolates collected from human patients between 2011 and 2012. RESULTS: All Salmonella spp. isolates were subjected to serotyping and antimicrobial susceptibility testing. Isolates displaying phenotypes and antimicrobial susceptibility profiles different from the reference strains were genotipically characterized. Several plasmid-embedded resistance determinants were identified and characterized. Non-typhoidal serotypes were most frequently diagnosed; monophasic Salmonella typhimurium 1,4 [5],12:i- and S. typhimurium represented the most prevalent serovars. Five isolates displayed phenotypes with extremely reduced susceptibility to antimicrobials: we detected multidrug resistance elements belonging to Ambler class A and class C in two non-typhoidal S. enterica serovars, i.e. Rissen and monophasic S. typhimurium 1,4 [5],12:i-, and in one typhoidal serovar, i.e., Paratyphi B. These resistance determinants have been so far almost exclusively associated with non-Salmonella members of the Enterobacteriaceae family. Alarmingly, two colistin resistant Salmonella enteritidis were also found. CONCLUSIONS: This work draws the attention to the still low, but rising, percentage of multidrug resistant Salmonella isolates infecting humans in Italy. Our results suggest that prompt monitoring of Salmonella serovar dissemination and resistance to antimicrobials is highly required. PMID- 27252786 TI - Optimized cultivation of Campylobacter concisus from gut mucosal biopsies in inflammatory bowel disease. AB - BACKGROUND: Campylobacter concisus is a commensal of the human oral flora that has been linked to prolonged diarrhea and inflammatory bowel disease (IBD). It has been detected more often from intestinal biopsies in patients with IBD compared to healthy controls using PCR-based techniques, whereas the number of C. concisus culture-positive biopsies in previous studies has been very limited. Determining the rate of viable isolates present in the gut mucosa is of great importance when evaluating the role in different disease presentations. We therefore investigated a novel two-step cultivation procedure combining anaerobic and microaerobic incubation from several gut mucosal sites to improve isolate yield, and compared this to PCR results, from IBD patients and healthy controls. RESULTS: Cultivation with the novel two-step procedure yielded a higher rate of C. concisus isolates from mucosal biopsies than previously reported by other methods. From 52 IBD patients, 52/245 (21 %) biopsies were culture positive for C. concisus, while 121/245 (49 %) of biopsies were PCR positive. For 26 healthy controls, the numbers were 23/182 (13 %) and 66/182 (36 %), respectively (p < 0.001). The rate of cultivation and PCR detection was higher for IBD patients compared to healthy controls (p = 0.021, p = 0.008, respectively). CONCLUSIONS: Patients with IBD had a higher prevalence of C. concisus than healthy controls, by both cultivation and PCR detection. We found a higher rate of C. concisus isolates from gut mucosal biopsies in both IBD patients and healthy controls than in preceding studies, indicating that colonization of C. concisus in the gastrointestinal tract is more extensive than previously assumed. PMID- 27252787 TI - Lixisenatide improves glycemic outcomes of Japanese patients with type 2 diabetes: a meta-analysis. AB - BACKGROUND: The GetGoal-L-Asia and -S trials were multi-center trials conducted in 4 and 16 countries, respectively including Japan that evaluated the efficacy and safety of lixisenatide add-on treatment vs. placebo among patients with type 2 diabetes. The aims of this study were to determine the efficacy and safety of lixisenatide add-on treatment among Japanese patient groups. METHODS: All Japanese intent-to-treat patients with baseline and endpoint HbA1c measurements were included in the meta-analyses. Subgroup analyses were carried out for patients with low (<8 %) and high (>=8 %) baseline HbA1c levels, low (<25 kg/m(2)) and high (>=25 kg/m(2)) baseline body mass index (BMI), short (<10 years) and long (>=10 years) durations of diabetes, and for those <65 and >=65 years of age. RESULTS: The overall study population of Japanese type 2 diabetes patients included 143 patients (mean age: 59.0 years; 35 % female) treated with lixisenatide and 136 patients treated with placebo (mean age: 57.8 years; 32 % female). Among the subgroups, lixisenatide treatment vs. placebo was associated with greater change in HbA1c (Low HbA1c -0.80 %, p < 0.0001; High HbA1c -1.19 %, p < 0.0001; low BMI -0.88 %, p < 0.0001; high BMI -1.28 %, p < 0.0001; short diabetes duration -1.28 %, p < 0.0001; long diabetes duration -0.93 %, p < 0.0001; <65 years: -1.00 %, p < 0.0001; >=65 years -1.24 %, p < 0.0001). Additionally, among the subgroups, lixisenatide treatment vs. placebo was associated with greater change in post-prandial glucose. CONCLUSIONS: For Japanese type 2 diabetes patients lixisenatide may be an efficacious and safe add on therapy leading to improved glycemic outcomes. GetGoal-L-Asia NCT01169779 GetGoal-S NCT00713830. PMID- 27252788 TI - Implications of using whole genome sequencing to test unselected populations for high risk breast cancer genes: a modelling study. AB - BACKGROUND: The decision to test for high risk breast cancer gene mutations is traditionally based on risk scores derived from age, family and personal cancer history. Next generation sequencing technologies such as whole genome sequencing (WGS) make wider population testing more feasible. In the UK's 100,000 Genomes Project, mutations in 16 genes including BRCA1 and BRCA2 are to be actively sought regardless of clinical presentation. The implications of deploying this approach at scale for patients and clinical services are unclear. In this study we aimed to model the effect of using WGS to test an unselected UK population for high risk BRCA1 and BRCA2 gene variants to inform the debate around approaches to secondary genomic findings. METHODS: We modelled the test performance of WGS for identifying pathogenic BRCA1 and BRCA2 mutations in an unselected hypothetical population of 100,000 UK women, using published literature to derive model input parameters. We calculated analytic and clinical validity, described potential health outcomes and highlighted current areas of uncertainty. We also performed a sensitivity analysis in which we re-ran the model 100,000 times to investigate the effect of varying input parameters. RESULTS: In our models WGS was predicted to identify correctly 93 pathogenic BRCA1 mutations and 151 BRCA2 mutations in 120 and 200 women respectively, resulting in an analytic sensitivity of 75.5-77.5 %. Of 244 women with identified pathogenic mutations, we estimated that 132 (range 121-198) would develop breast cancer, so could potentially be helped by intervention. We also predicted that breast cancer would occur in 41 women (range 36-62) incorrectly identified with no pathogenic mutations and in 12,460 women without BRCA1 or BRCA2 mutations. There was considerable uncertainty about the penetrance of mutations in people without a family history of disease and the appropriate threshold of absolute disease risk for clinical action, which impacts on judgements about the clinical utility of intervention. CONCLUSIONS: This simple model demonstrates the need for robust processes to support the testing for secondary genomic findings in unselected populations that acknowledge levels of uncertainty about the clinical validity and clinical utility of testing positive for a cancer risk gene. PMID- 27252789 TI - Acute Prevertebral Calcific Tendinitis. AB - We present a case of neck pain in a middle-aged woman, initially attributed to a retropharyngeal infection and treated with urgent intubation. With the help of computed tomography, the diagnosis was later revised to acute prevertebral calcific tendinitis, a self-limiting condition caused by abnormal calcium hydroxyapatite deposition in the longus colli muscles. It is critical to differentiate between these two disease entities due to dramatic differences in management. A discussion of acute prevertebral calcific tendinitis and its imaging findings is provided below. PMID- 27252791 TI - Unusual Pulmonary Arterial Filling Defect caused by Systemic to Pulmonary Shunt in the Setting of Chronic Lung Disease Demonstrated by Dynamic 4D CTA. AB - Even though pulmonary embolism is by far the most common cause of filling defect in the pulmonary arterial system, other less common etiologies should be considered especially in the setting of atypical clinical scenario or unusual imaging findings. Unusual pattern of filling defect in the pulmonary artery in the setting of chronic inflammatory/fibrotic parenchymal lung disease should raise the concern for systemic to pulmonary artery shunt. This diagnosis is typically made by conventional angiography. Dynamic 4D CT angiography however can be a safe, noninvasive and effective alternative tool for making such a diagnosis. It has the added value of multiplanar reconstruction capabilities and providing detailed anatomy which can be vital for interventional radiologists when planning their approach for possible intervention. We present 2 cases of such shunts, and illustrate the demonstration of these shunts by using dynamic 4D CT angiography. PMID- 27252790 TI - Rosai-Dorfman Disease Isolated to the Thoracic Epidural Spine. AB - Rosai-Dorfman disease is a rare benign histiocytic disease that infrequently presents in the spine. We report a case of Rosai-Dorfman disease isolated to the epidural thoracic spine in a 26-year-old male. To our knowledge, this is the 15th reported case of isolated spinal disease and only the fourth case of isolated thoracic epidural disease. Given its rarity as well as non-specific symptoms and imaging findings, Rosai-Dorfman disease is often not considered and misdiagnosed on imaging studies. To help improve awareness of Rosai-Dorfman spinal disease, we review the literature and discuss the epidemiology, clinical presentation, imaging features, and treatment considerations for this condition. PMID- 27252792 TI - Aberrant systemic arterial supply to normal lung arising from the proper hepatic artery discovered during transarterial chemoembolization. AB - We report a rare case of dual arterial supply to an otherwise normal lung discovered incidentally during initial angiography performed with the intent of chemoembolization of hepatocellular carcinoma. In addition to normal hepatic arterial supply, the proper hepatic artery provided systemic arterial supply to the lower lobe of the left lung. Subsequent chest computed tomography angiography demonstrated a normal tracheobronchial tree and normal pulmonary arterial supply to the lung. Although other anatomic variants have been reported, there are no other reported cases of systemic arterial supply from the proper hepatic artery to the lung. Identifying systemic arterial supply to the lung during angiography is important while performing transcatheter chemoembolization or radioembolization in the liver in order to minimize non-target embolization of the lung. PMID- 27252793 TI - Idiopathic Arterial Calcification of Infancy: Case Report. AB - Idiopathic arterial calcification of infancy is a rare autosomal recessive disease, characterized by deposition of calcium along the internal elastic membrane of arteries, accompanied by fibrous thickening of the intima which causes luminal narrowing. Here we are reporting a case of idiopathic arterial calcification of infancy in a Saudi female newborn of non-consanguineous pregnant woman who had polyhydramnios. The newborn baby had severe respiratory distress, systemic hypertension and persistent pulmonary hypertension of newborn. She was admitted to Neonatal Intensive Care Unit, where she was ventilated and proper treatment was provided. Molecular genetic testing was positive for mutations of ectonucleotide pyrophosphatase/phosphodiesterase1 gene which is reported in 80% of cases of Idiopathic arterial calcification of infancy. The baby died at about 5 month of age because of myocardial ischemia and cardiorespiratory arrest. Idiopathic Arterial Calcification of Infancy should be considered in any newborn who presented with persistent pulmonary hypertension of newborn, severe systemic hypertension and echogenic vessels on any radiological study. Calcifications of large and medium-sized arteries are important diagnostic finding. PMID- 27252794 TI - Visualizing the quality of partially accruing data for use in decision making. AB - Secondary use of clinical health data for near real-time public health surveillance presents challenges surrounding its utility due to data quality issues. Data used for real-time surveillance must be timely, accurate and complete if it is to be useful; if incomplete data are used for surveillance, understanding the structure of the incompleteness is necessary. Such data are commonly aggregated due to privacy concerns. The Distribute project was a near real-time influenza-like-illness (ILI) surveillance system that relied on aggregated secondary clinical health data. The goal of this work is to disseminate the data quality tools developed to gain insight into the data quality problems associated with these data. These tools apply in general to any system where aggregate data are accrued over time and were created through the end-user-as-developer paradigm. Each tool was developed during the exploratory analysis to gain insight into structural aspects of data quality. Our key finding is that data quality of partially accruing data must be studied in the context of accrual lag-the difference between the time an event occurs and the time data for that event are received, i.e. the time at which data become available to the surveillance system. Our visualization methods therefore revolve around visualizing dimensions of data quality affected by accrual lag, in particular the tradeoff between timeliness and completion, and the effects of accrual lag on accuracy. Accounting for accrual lag in partially accruing data is necessary to avoid misleading or biased conclusions about trends in indicator values and data quality. PMID- 27252795 TI - Characterizing the Access of Clinical Decision Support Offered by Immunization Information System in Minnesota. AB - BACKGROUND: Healthy People 2020 aims to improve population health by increasing immunization rates to decrease vaccine-preventable infectious diseases. Amongst the many strategies, role of immunization information systems (IIS) are recognized by studies and taskforce reports. IIS are unique in their offering of clinical decision support for immunizations (CDSi) which are utilized by healthcare providers. Federal initiatives such as Meaningful Use (MU) and Affordable Care Act (ACA) aim to improve immunization rates through use of technology and expanding access to immunization services respectively. MU, the Electronic Health Record (EHR) incentive program includes use of IIS CDSi functionality as part of Stage 3. It is essential to understand access and use patterns of IIS CDSi, so as to utilize it better to improve immunization services. OBJECTIVES: To understand the utilization of clinical decision support for immunizations (CDSi) offered by immunization information system in Minnesota and to analyze the variability of its use across providers and EHR implementations. METHODS: IIS in Minnesota (Minnesota Immunization Information Connection: MIIC) offers CDSi that is accessed through EHRs and branded as Alternate Access (AA). Data from MIIC and technical documents were reviewed to create details on organizations which implemented AA functionality. Data on EHR adoption in clinics and local health departments was obtained from Minnesota eHealth assessment reports. Data on access were tracked from January 2015 through mid-October 2015 through weekly specialized reports to track the queries by organization, volume and day of the week. Data were analyzed, findings were synthesized and reviewed with subject matter experts. RESULTS: Currently 25 healthcare systems/organizations which represent 599 individual provider sites have implemented the AA functionality. Analysis of their EHR platform pointed to two EHRs (Epic and PH-Doc) as dominant products in Minnesota for private and public providers respectively. Use of this function was even across study time period. The query volume correlated to size of the organization, with the exception of an outlier organization with huge query count. Query was able to successfully locate a single matching record for 59% of searches, could not find a record for 5% and 31% resulted in blank/error and the match rates varied across health systems. CONCLUSION: High EHR adoption offers a great opportunity to promote use of IIS CDSi at point of care. Analysis did not track use at individual clinic level and how the queries were being generated. Additional research is needed to understand the provider level use of this CDSi and other organizational and technical factors which influence access to IIS. This is essential for IIS as they execute projects to improve population-level immunization rates, plan provider outreach and prioritize their system enhancements to meet federal requirements. PMID- 27252796 TI - Foreword to the CLER National Report of Findings 2016. PMID- 27252797 TI - Introduction to the CLER National Report of Findings 2016. PMID- 27252798 TI - The Overview of the CLER Program: CLER National Report of Findings 2016. PMID- 27252799 TI - The Methodology for the CLER National Report of Findings 2016. PMID- 27252800 TI - The Overarching Themes from the CLER National Report of Findings 2016. PMID- 27252801 TI - Challenges and Opportunities in the Six Focus Areas: CLER National Report of Findings 2016. PMID- 27252802 TI - Detailed Findings from the CLER National Report of Findings 2016. PMID- 27252804 TI - Appendices. PMID- 27252803 TI - Lessons Learned and Future Directions: CLER National Report of Findings 2016. PMID- 27252805 TI - Microbial and Antibiotic Susceptibility Profile among Clinical Samples of Patients with Acute Leukemia. AB - INTRODUCTION: Preventing and starting early treatment of infections in patients whose immunity system is weak due to malignancies like leukemia can reduce mortality. This study aimed to determine microbial and antibiotic resistance patterns in clinical samples of patients with acute leukemia to start early treatment before the results of clinical tests are known. SUBJECTS AND METHODS: In this cross-sectional study, the clinical samples of all patients hospitalized with the diagnosis of acute leukemia were cultured and their antibiogram was evaluated. Then, the data were analyzed by SPSS 18 based on the objectives of the study. RESULTS: Of a total of 2,366 samples, 18.95% were reported to be positive blood samples, 22.96% were reported to be urine samples and 36% wound samples. E. coli was the most common bacteria isolated from the blood and urine cultures (34% in blood, 32% in urine culture) while Staphylococcus Aureus was the most common in the wound culture (35%). The highest level of sensitivity in the organisms with positive blood culture was to Ciprofloxacin, while in positive urine and wound culture was to Imipenem. The highest resistance in blood, urine and wound culture was to Cotrimoxazole. CONCLUSION: According to results obtained from this study, it is necessary to conduct appropriate studies on this issue in specific conditions in our country. The findings of this study can be used in clinics for more accurate diagnosis, more effective treatment before the results of clinical tests are known and also for prevention of infection in cancer patients. PMID- 27252806 TI - JAK2V617F Allele Burden Measurement in Peripheral Blood of Iranian Patients with Myeloproliferative Neoplasms and Effect of Hydroxyurea on JAK2V617F Allele Burden. AB - BACKGROUND: Myeloproliferative neoplasms (MPNs) are clonal malignant diseases that represent a group of conditions including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The aim of this study was to evaluate possible correlations between JAK2V617F allele burden and clinicohematologic characteristics in Iranian patients with MPNs. We also aimed at determining the correlation between JAK2V617F allele burden and use of cyto reductive treatment (hydroxyurea). MATERIALS AND METHODS: We performed ARMS-PCR for all MPNs samples and subsequently performed real-time quantitative polymerase chain reaction (qRT-PCR) for JAK2V617F allele burden measurement using DNA from peripheral blood leukocytes. RESULTS: Two distinct groups of patients were examined at a single time point: group A (n=40; 20 PV, 20 ET) was examined at the time of diagnosis; group B (n=85; 40 PV, 30 ET and 15 PMF) while under treatment with hydroxyurea (HU). The median allele burden of the JAK2 V617F was 72% for PV and 49% for ET patients at the time of diagnosis (p=0.01). For patients with HU treatment, we determined the median JAK2V617F allele burden to be 43%, 40%, and 46.5 % in PV, ET and PMF patients; respectively. HU-treated PV patients had a significant lower %JAK2V617F than PV patients at the time of diagnosis (43% vs. 72%, p=0.005). In ET group, the relationship between the JAK2 V617F allele burden and leukocyte count was significant (p=0.02 and p=0.01 in untreated and treated patients, respectively). CONCLUSIONS: Our results showed that patients with PV have a higher JAK2V617F allele burden. Moreover, our study demonstrated that the JAK2V617F allele burden correlates with clinical features in ET group. We also showed hydroxyurea can affect the JAK2V617F allele burden in PV patients. PMID- 27252807 TI - The Relationship between Self-esteem and Quality of Life of Patients with Idiopathic Thrombocytopenic Purpura at Isfahan's Sayed Al-Shohada Hospital, Iran, in 2013. AB - BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is a chronic disease which is accompanied with hopelessness and loss of the sense of well-being due to its symptoms and treatment. It also affects patients' sense of social and spiritual well-being. This disorder decreases patients' self-esteem and their quality of life by changing their mental image and self-confidence. This study was performed to find the relationship between self-esteem and quality of life of patients with ITP. SUBJECTS AND METHODS: This was a descriptive-analytical study on 64 patients with ITP who referred to Isfahan's Sayed Al-Shohada Hospital, Iran. In this study, patients with ITP were selected randomly using a random number chart. The data collection tools consisted of the World Health Organization Quality of Life (WHOQOL)-BREF and Coopersmith Self-esteem Inventory (CSEI). Data were analyzed using SPSS and chi-square and Mann-Whitney tests and the Pearson and Spearman's rank correlation coefficients. RESULTS: In total, 64 patients completed the questionnaires. RESULTS showed that 32% of subjects were over 36 years of age and 59% were women. In addition, 29.7% of ITP patients had low self-esteem and quality of life. Chi-square test showed a significant relationship between self esteem and quality of life of patients with ITP. CONCLUSIONS: The results of the present study showed that considerable attention must be paid to self-esteem, as one of the most important factors influencing the promotion of quality of life. Therefore, it is suggested that patient's self-esteem be improved by the implementation of educational and psychological programs in order to decrease the consequences of poor quality of life. PMID- 27252808 TI - Granulocyte Colony-Stimulating Factor Use in a Large Iranian Hospital: Comparison with American Society of Clinical Oncology (ASCO) Clinical Practice Guideline. AB - BACKGROUND: Granulocyte Colony Stimulating Factors (GCSF) is high-cost agents commonly recommended for primary and secondary prophylaxis of chemotherapy induced neutropenia and febrile neutropenia. GCSFs have been shown to be beneficial in some patient subgroups, although they are probably overused in clinical settings. The American Society of Clinical Oncology (ASCO) guidelines summarize current data on the appropriate use of CSFs. The aim of this study was to assess and audit the use of GCSF in a tertiary care center according to the recommendation of ASCO guideline. SUBJECTS AND METHODS: A prospective observational study from November 2014 to June 2015 was performed on all patients prescribed with filgrastim in the large teaching hospital (Isfahan, Iran). Data was collected on demographics, indication, dosing regimen and duration of treatment, the Absolute Neutrophil Count (ANC) and patient outcome. RESULTS: 91 patients were recorded over the period of the study. 63.7% of prescription complied with the ASCO guideline. Febrile neutropenia post chemotherapy/radiotherapy was the most common appropriate indication (29.3%) followed by primary prophylaxis (25.8%). Fourteen (32%) patients showed ANC recovery in 1-3 days and 16 (37%) within 4-7 days. Ten patients (23%) showed no recovery. The overall mortality was 8 (8.8%) patients. CONCLUSION: This study revealed that at least one-third of prescribed GCSF was not in accordance with ASCO guideline. Considering the high cost of GCSF in our country and limitation of our resources, we proposed cost-effectiveness studies on GCSF treatment and also the development of a national guideline for optimizing GCSF use. PMID- 27252809 TI - Clinical Manifestations of beta-Thalassemia Major in Two Different Altitudes; Bushehr and Shahrekord. AB - BACKGROUND: Patients with beta-thalassemia major (TM) develop iron overload through increased iron absorption and transfusional therapy and it's the most important complication of TM. Thalassemia is common in coastal regions and lands with low altitudes. The aim of this study is to determine the effect of high and low altitude on serum ferritin and treatment requirement in two groups of beta thalassemia major (TM) patients. SUBJECTS AND METHODS: Patients were divided into two groups, the first group (No: 50) living at sea level (in the port of Bushehr, Iran) and the second group (No: 40) living at the altitude of 2061 m (in the city of Shahrekord, Iran). All patient's clinical history, blood transfusion and laboratory tests including complete blood count and hemoglobin electrophoresis were reviewed. RESULTS: There were no significant difference in ferritin levels, transfusion period and diabetes incidence of the two cities patients (P>0.05). Patient's cardiac function and liver condition were significantly better in patients of Bushehr (P<0.05). Patients under 20 years in Bushehr were less splenectomized in comparison with Shahrekord (P<0.05). CONCLUSION: Our result showed that some of clinical manifestations of patients in low altitude such as cardiac and liver condition were better. But it did not affect ferritin level probably due to transfusion and chelating therapy. Totally patients of Bushehr had better conditions and had longer survivals. PMID- 27252810 TI - In Vitro Effects of Propranolol on T Helper Type 1 Cytokine Profile in Human Leukemic T Cells. AB - INTRODUCTION: Cytokines are a large group of proteins play a key role in inflammation. Down-regulation of pro-inflammatory cytokines has beneficial effect on heart function. Propranolol, as a non selective beta-adrenergic blocker, has been extensively used for treatment of many cardiovascular problems such as arrhythmias and heart malfunction. In addition anti-inflammatory effects of propranolol have been revealed. In this study the propranolol effect on T helper type 1 cytokine profile in human leukemic T cells has been assessed in vitro. MATERIALS AND METHODS: Human leukemic T cells (Molt-4 and Jurkat) were cultured in complete RPMI medium. The cells were then incubated with different concentrations of propranolol (0.03- 30 uM) in the presence or absence of PHA (10 ug/ml) for 48 hours. The supernatants of cell culture media were collected and used for cytokines assay. RESULTS: Propranolol significantly decreased the T helper type 1 cytokine profile [Interleukin-2 (IL-2) and Interferon- gamma (IFN gamma)] production in PHA stimulated Molt-4 and Jurkat cells, after 48 hour of incubation time, dose-dependently compared to untreated control cells. CONCLUSION: Our data showed a dose dependent inhibitory effect of propranolol on the IL-2 and IFN-gamma production in human leukemic Molt-4 and Jurkat cells. The anti- inflammatory effect of propranolol reported by other investigators may be in part due to its suppressive effect on production of inflammatory cytokines such as IL-2 and IFN-gamma. So, propranolol along with its chronic long-term usage in cardiovascular problems may have potential implication in treatment of inflammatory-based disorders. PMID- 27252811 TI - Bilateral Maxillary, Sphenoid Sinuses and Lumbosacral Spinal Cord Extramedullary Relapse of CML Following Allogeneic Stem Cell Transplant. AB - Isolated extramedullary relapse of chronic myelogenous leukemia (CML) after allogeneic stem cell transplant is rare. There is a case report of a child who developed a granulocytic sarcoma of the maxillary and sphenoid sinuses and lumbosacral spinal cord mass 18 months after allogeneic bone marrow transplant for CML. He was presented with per orbital edema and neurological deficit of lower extremities and a mass lesion was found on spinal cord imaging. No evidence of hematologic relapse was identified at that time by bone marrow histology or cytogenetic. The patient died 1 month later with a picture of pneumonia, left ventricular dysfunction and a cardiopulmonary arrest on a presumed underlying sepsis with infectious etiology. Granulocytic sarcoma should be considered in the differential diagnosis of mass lesions presenting after allogeneic bone marrow transplantation for CML, even if there is no evidence of bone marrow involvement. PMID- 27252812 TI - A Case of Multiple Myeloma Following Bladder Cancer. AB - Second primary malignancy following multiple myeloma (MM) was reported several years ago. There are also rare reports of cases with synchronous MM and other malignancies. To our knowledge, only one case of MM following bladder cancer has been reported in the literature. Here, we report the second case occurred three months after diagnosis of bladder cancer. PMID- 27252813 TI - Approach to the Triple Negative Breast Cancer in New Drugs Area. AB - Triple negative breast cancers (TNBCs) are associated with aggressive course, higher rates of visceral and central nervous system metastases and lower survival rate than hormone receptor positive. Once metastasis has occurred, a median survival was approximately one year. Currently, chemotherapy in TNBC is similar to other HER2- negative breast cancers but in the near future, it will revolutionize. TNBCs are quite heterogeneous based on biomarkers and genetic variations. The series of new drugs have been tried; in this article, platinum, anti-epigenetic drugs, PARP inhibitors, epidermal growth factor receptor inhibitor, Src family kinase inhibitor, anti androgen, glycoprotein Non metastatic melanoma B (gpNMB) antibody, LHRH conjugated to cytotoxic drugs and inhibition of the PI3K/AKT/mTOR pathway will be explained. What is the optimal therapy for TNBC patients? It is still not clear but it seems that the road map according to biological and genetic markers is taking shape. PMID- 27252815 TI - The Diagnostic Role of Magnetic Resonance Enterography as a Complementary Test to Colonoscopy in Active Crohn's Disease. AB - BACKGROUND According to recent studies comparing magnetic resonance enterography (MRE) with ileocolonoscopy for assessing inflammation of small bowel and colonic segments in adults with active Crohn's disease (CD), we aimed to compare the accuracy of these two diagnostic methods in Iranian population. METHODS During 2013-2014 a follow-up study was done on 30 patients with active CD in a gastroenterology clinic affiliated to Tehran University of Medical Sciences. MRE and ileocolonoscopy were performed for all the patients. All statistical analyses were performed using SPSS (version 18) and p-value<0.05 was considered as statistically significant. RESULTS Of the 30 patients with active CD, 11(36.7%) were men and 19 (63.3%) were women with mean age of 37.30+/-13.66 years (range: 19-67 years). MRE had sensitivity and specificity of 50% and 90% with positive predictive value (PPV) and negative predictive value (NPV) of 71.43 and 78.26, respectively for localizing sigmoid lesions and ileum had sensitivity and specificity of 84.21 and 45.45 with PPV and NPV of 72.73 and 62.50, respectively. CONCLUSION While moderate sensitivity and high specificity of MRE in localizing colonic lesions makes it an appropriate confirmatory test after colonoscopy, the reported high sensitivity and moderate specificity of MRE versus colonoscopy in detecting ileal lesions makes it a suitable screening test for ileal lesions. Finally we can conclude that MRE can be an important complementary test to colonoscopy in detecting active disease. PMID- 27252814 TI - Pathological and Clinical Correlation between Celiac Disease and Helicobacter Pylori Infection; a Review of Controversial Reports. AB - There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection. PMID- 27252816 TI - Solid Pseudopapillary Neoplasm of Pancreas; A Case Series and Review Literature. AB - BACKGROUND Information regarding solid pseudopapillary neoplasm (SPN) of the pancreas is limited in Iran. We aimed to review the clinicocytopathological features and follow-up of patients with SPN of pancreas who were diagnosed in a single center in Iran. METHODS Seven patients with SPN of the pancreas were diagnosed during January 2010 to March 2015 at the Digestive Disease Research Institute of Tehran University of Medical Sciences. The patients were reviewed prospectively. RESULTS Six out of the 7 patients were female and the mean age of all the patients was 29.4 years ranging from 15 to 61 years. The most common clinical presentation was nonspecific abdominal pain (N=6). The tumors were located mostly in head and neck of the pancreas. SPN was diagnosed in all patients by fine needle aspiration through endosonography (EUS-FNA). All patients underwent surgery. Histological findings of surgical tissues were consistent with EUS-FNA. The postoperative follow-up period of about 14 months was uneventful. CONCLUSION SPN of the pancreas is a rare pancreatic tumor which affects primarily young women. EUS-guided FNA could play an important role in preoperative diagnosis of SPN of the pancreas. PMID- 27252817 TI - An Accessible and Pragmatic Experimental Model of Nonalcoholic Fatty Liver Disease. AB - BACKGROUND There is no convenient cheap pragmatic experimental model for Nonalcoholic Fatty Liver Disease (NAFLD)/Nonalcoholic Steatohepatitis (NASH). OBJECTIVE: Our objective was to create a pragmatic model of NAFLD/NASH. METHODS Sprague-Dawley rats were fed a high-fat, high sugar homemade diet ad libitum for seven weeks. The high-fat, high sugar diet included 59% of energy derived from fat, 30% from carbohydrates, and 11% from protein. Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes, insulin, and hepatic tumor necrosis factor-alpha (TNF-alpha) gene expression were determined. Hepatic histology was examined by H&E stain. RESULTS Rats fed the high-fat, high sugar diet developed hepatic steatosis, and a moderate inflammation, which was associated with increased serum levels of liver enzymes, glucose, insulin, triglyceride, cholesterol, and hepatic TNF-alpha gene expression. CONCLUSION This rat model resembles the key features of human NAFLD/NASH and provides a simple pragmatic experimental model for elucidating the disease prevention and treatment. PMID- 27252818 TI - Nonadherence to Medication in Inflammatory Bowel Disease: Rate and Reasons. AB - BACKGROUND This study is the first study to evaluate the nonadherence rate and reasons of same patient with inflammatory bowel disease (IBD) in Iran. METHODS During 9 months, 500 patients with IBD were enrolled in the study. Patients were interviewed about their nonadherence behaviors. Factor analysis was used to analyze the collected answers. RESULTS The overall rate of nonadherence was 33.3% (27.6% intentional nonadherence and 5.7% unintentional nonadherence). 33.6% of the patients had at least one relapse after discontinuing treatment. The most frequent reason for intentional nonadherence was discontinuing the treatment after recovering from symptoms (42.7%). The most frequent reason for unintentional nonadherence was forgetfulness (5.2%). 19.8% of the patients did not visit their gastroenterologist on time and they purchased drugs from the drugstore. These patients reported that their clinics were too far and difficult to access. There was no significant relationship between nonadherence and demographic variables. CONCLUSION Multiple reasons are suggested as factors of medication nonadherence and they seem to be different among different populations. Determining these possible reasons, could lead to finding suitable strategies to overcome or reduce them. PMID- 27252819 TI - Inverse Association of Plasma Level of Glutathione Peroxidase with Liver Fibrosis in Chronic Hepatitis B: Potential Role of Iron. AB - BACKGROUND Oxidative stress has a major pathogenic role for liver damage following chronic hepatitis B. Glutathione peroxidase (Gpx) is necessary in oxidative state mechanism that is generally down-regulated by Hepatitis B virus (HBV) infection. On the other hand, disorders of iron homeostasis have been found out in HBV infected patients. Therefore, the objective of this study was to assess the interplay of Gpx and serum iron on clinical and virological features of patients with chronic HBV infection. METHODS One hundred and fifty adult, treatment-naive, patients with chronic hepatitis B were randomly designated from an ongoing cohort of patients with HBV. Plasma Gpx1 concentration and HBV DNA quantity were measured. Liver stiffness was measured by transient elastography. RESULTS Serum iron had a positive association with HBV DNA count in the total population. Serum iron was not associated with liver stiffness. However, HBV DNA was significantly associated with liver stiffness only in male patients. Serum Gpx was inversely associated with liver stiffness. Serum iron and Gpx had indirect effects on liver stiffness via HBV DNA count. We observed dissimilar effects of serum iron on HBV DNA and Gpx on liver stiffness in male and female patients. CONCLUSION We identified interplay of serum iron and Gpx1 in relation to level of liver fibrosis in patients with chronic hepatitis B. Our results propose that oxidative stress and serum iron are differentially implicated in the progression of chronic hepatitis B in male and female patients. PMID- 27252820 TI - The Prevalence of Metabolic Syndrome In Non-alcoholic Fatty Liver Disease; A Population-Based Study. AB - BACKGROUND Some evidence, not in large study populations, suggests that nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) share common interactions. We aimed to determine the prevalence of NAFLD and MetS in a large population registered to Kavar Cohort Study center. We also assessed the role of each component of MetS in NAFLD existence. METHODS Data were obtained from 3415 volunteers who called and refereed to our center. Complete anthropometric and laboratory measurement and abdominal ultrasonography was done for these individuals to screen NAFLD and its grade. A questionnaire was also used to obtain information on demographical and medical history and alcohol consumption. MetS was defined in all participants based on the National Cholesterol Education Program Adult Treatment Panel III (2001) (NCEP/ATP-III) and criteria for clinical diagnosis of metabolic syndrome in Iranian adults (CCDMIA). RESULTS Among the refereed individuals, 2980 peoples were aged >=18 years with male to women ratio of 1:2.45. NAFLD was diagnosed by ultrasound in 32.9% and 27.4% of men and women, respectively. MetS was detected in 65.9 and 64.6 of the patients with NAFLD (based on NCEP/ATP-III) and in 30.1% and 73.7% (based on CCDMIA) of men and women, respectively. There were no significant differences between two gender in none of the components (p>0.05). Although, OR for hyperglycemia and abdominal obesity were approximately high in CCDMIA criteria (0.9613 and 1.2082, respectively), the differences were not statistically significant. CONCLUSION NAFLD was associated with MetS. However, it was not possible to determine whether NAFLD predating the development of MetS. PMID- 27252821 TI - Fever,Weight Loss and Early Satiety due to Gastric Inflammatory Myofibroblastic Tumor; Case Report and Literature Review. AB - Gastric inflammatory myofibroblastic tumor (IMT) is a rare tumor with and unpredictable prognosis usually find in young adults. We present an 18-yearold man with gastric IMT. He complained of epigastric pain, intermittent fever and night sweating associated with weight loss since two years ago. Physical examination showed anemic and cachestic features with mild abdominal tenderness in palpitation as well as an abdominal mass in epigastrium. Abdominal CT scan revealed a huge mass that was arising from the stomach. Upper endoscopy revealed a submucosal lesion in fundus of stomach of approximately 8cm. Endoscopic ultrasound showed a large sub-mucosal non homogenous fundal mass with areas of calcification. The patient underwent laparoscopic partial gastrectomy. Histopathologyand immunohistochemistryevaluation revealed an IMT. PMID- 27252822 TI - Juvenile Hemochromatosis in Iran: A Case Report with 5-Year Follow-up after Treatment. AB - Juvenile hemochromatosis is a rare autosomal recessive disorder that typically occurs in the first to third decades of life. Its symptoms are more acute and severe than classic hemochromatosis. We describe a 27-year-old man who was referred to the gastrointestinal clinic with a probable diagnosis of fatty liver and was finally diagnosed as having juvenile hemochromatosis. A review of the scientific literature reveals that recently only three siblings suffering from the disease have been reported in Iran. PMID- 27252823 TI - Is occult Hepatitis B virus infection with detectable anti-HBs infectious or not? PMID- 27252824 TI - An Uncommon Cause of Splenomegaly. PMID- 27252825 TI - A designed DNA binding motif that recognizes extended sites and spans two adjacent major grooves. AB - We report the rational design of a DNA-binding peptide construct composed of the DNA-contacting regions of two transcription factors (GCN4 and GAGA) linked through an AT-hook DNA anchor. The resulting chimera, which represents a new, non natural DNA binding motif, binds with high affinity and selectivity to a long composite sequence of 13 base pairs (TCAT-AATT-GAGAG). PMID- 27252826 TI - Exogenous H2S modulates mitochondrial fusion-fission to inhibit vascular smooth muscle cell proliferation in a hyperglycemic state. AB - AIM: Vascular smooth muscle cell (VSMC) proliferation in response to hyperglycemia is an important process in the development of arterial vessel hyperplasia. The shape change of mitochondria is dynamic and closely related to fission and fusion. Hydrogen sulfide (H2S) was confirmed to have anti-oxidative, anti-inflammatory and anti-proliferative effects. However, little it is known about its effects on mitochondrial morphology induced by hyperglycemia. The aim of the study is to demonstrate that H2S inhibits VSMC proliferation through regulating mitochondrial fission. METHODS AND RESULTS: We observe lower H2S levels as well as higher proliferative protein expression levels for proliferative cell nuclear antigen (PCNA) and cyclin D1 and higher mitochondrial fusion-fission protein expression levels for dynamin-related protein 1 (Drp 1) in human kidney arteries and in db/db mouse aorta. Exogenous H2S (100 MUM NaHS) inhibits vascular smooth muscle cells of human pulmonary aorta(HPASMC) proliferation and migration in response to high glucose using the BrdU and scratch wound repair assays, decreases proliferative protein (PCNA and cyclin D1) expression, and reduces ROS production in the cytoplasm and mitochondria. When HPASMCs proliferate with a high glucose treatment, the mitochondria become small spheres with a short rod-shaped structure, whereas NaHS, a mitochondrial division inhibitor and siDrp prevent VSMC proliferation and maintain mitochondria as stationary and randomly dispersed with fixed structures. CONCLUSION: Exogenous H2S aids in inhibiting mitochondrial fragmentation and affects proliferation in db/db mice and HPASMCs by decreasing Drp 1 expression. PMID- 27252827 TI - Paeoniflorin protects diabetic mice against myocardial ischemic injury via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway. AB - BACKGROUND: Diabetes mellitus has multiple complications including neuropathy and increases cardiovascular events. Paeoniflorin (PF), a monoterpene glycoside, plays an essential role in neuroprotection and ischemic heart disease. In this study, we aimed to investigate the hypothesis that PF protects mice with diabetes mellitus against myocardial ischemic injury, and determine its associated mechanisms. RESULTS: Myocardial infarction (MI) was generated in the streptozotocin-mediated diabetic mice, which were pretreated with either vehicle or PF, respectively. Myocardial infarct size, myocardial enzyme, cardiac function, circulating calcitonin gene-related peptide (CGRP) concentration, histological analysis and the expression of associated molecules were determined and compared among different experimental groups. Compared to diabetic hearts pretreated with vehicle, hearts pretreated with PF exhibited less tissue damage and better CGRP concentration in serum when subjected to myocardial ischemia. Transient receptor potential vanilloid 1(TRPV1) gene knockout attenuated PF mediated cardioprotection. Moreover, a specific Ca(2+)/calmodulin-dependent protein kinase (CaMK) inhibitor, KN-93, increased tissue damage and decreased CGRP activity in serum. Meanwhile, pretreated with PF increased the phosphorylation of cAMP response element binding protein (CREB). CONCLUSIONS: Taken together, these findings demonstrate that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway. PMID- 27252828 TI - Match injuries in amateur Rugby Union: a prospective cohort study - FICS Biennial Symposium Second Prize Research Award. AB - BACKGROUND: The majority of Rugby Union (rugby) players participate at the amateur level. Knowledge of player characteristics and injury risks is predominantly ascertained from studies on professional or junior athletes in rugby. The objectives of the current study are to: (1) describe the health related quality of life (HRQoL) and physical characteristics of a cohort of amateur rugby players; (2) describe the incidence, severity and mechanism of match injuries in amateur rugby, and; (3) explore factors associated with rates of match injury in this population. METHODS: Participants (n = 125) from one amateur men's rugby club were followed in a one-season (2012) prospective cohort study. Match injury and match time exposure data were collected. A participant match exposure log was maintained. Baseline variables collected include: participant's age, playing experience, position of play, the SF-36v2 health survey, height and weight. Injury incidence rates (IIRs) per 1000 match-hours exposure were calculated. Injury sub-groups were compared by calculating rate ratios of two IIRs. Poisson mixed-effects generalised linear modelling was used to explore relationships between IIRs and baseline predictors. RESULTS: A total of 129 injuries occurred during a combined period of 2465 match-hours of exposure. The overall IIR was 52.3 (43.7-62.2) /1000 match-hours exposure. Moderate-severe injuries (>1 week time-loss from play) comprised 36 % of all injuries. Tackling was the most common mechanism of injury, the head/face was the most common body region of injury and sprain/ligament injuries were the most common injury type. Fewer years of rugby participation, lower BMI and lower SF 36v2 mental component summary score were associated with higher IIR in amateur rugby. Age, player position i.e., backs versus forwards and SF-36v2 physical component summary score were not associated with injury incidence. CONCLUSION: Amateur rugby players report similar HRQoL as the general population. We found amateur players had a higher rate of injury and lower injury severity than previous amateur studies, but location, type, and mechanism were similar. In this study pre-season HRQoL and BMI were weakly associated with higher injury rate when controlling for other factors; a finding that should be interpreted with caution and clarified with future research. PMID- 27252829 TI - A simple method to predict body temperature of small reptiles from environmental temperature. AB - To study behavioral thermoregulation, it is useful to use thermal sensors and physical models to collect environmental temperatures that are used to predict organism body temperature. Many techniques involve expensive or numerous types of sensors (cast copper models, or temperature, humidity, radiation, and wind speed sensors) to collect the microhabitat data necessary to predict body temperatures. Expense and diversity of requisite sensors can limit sampling resolution and accessibility of these methods. We compare body temperature predictions of small lizards from iButtons, DS18B20 sensors, and simple copper models, in both laboratory and natural conditions. Our aim was to develop an inexpensive yet accurate method for body temperature prediction. Either method was applicable given appropriate parameterization of the heat transfer equation used. The simplest and cheapest method was DS18B20 sensors attached to a small recording computer. There was little if any deficit in precision or accuracy compared to other published methods. We show how the heat transfer equation can be parameterized, and it can also be used to predict body temperature from historically collected data, allowing strong comparisons between current and previous environmental temperatures using the most modern techniques. Our simple method uses very cheap sensors and loggers to extensively sample habitat temperature, improving our understanding of microhabitat structure and thermal variability with respect to small ectotherms. While our method was quite precise, we feel any potential loss in accuracy is offset by the increase in sample resolution, important as it is increasingly apparent that, particularly for small ectotherms, habitat thermal heterogeneity is the strongest influence on transient body temperature. PMID- 27252830 TI - Phylogenetic assemblage structure of North American trees is more strongly shaped by glacial-interglacial climate variability in gymnosperms than in angiosperms. AB - How fast does biodiversity respond to climate change? The relationship of past and current climate with phylogenetic assemblage structure helps us to understand this question. Studies of angiosperm tree diversity in North America have already suggested effects of current water-energy balance and tropical niche conservatism. However, the role of glacial-interglacial climate variability remains to be determined, and little is known about any of these relationships for gymnosperms. Moreover, phylogenetic endemism, the concentration of unique lineages in restricted ranges, may also be related to glacial-interglacial climate variability and needs more attention. We used a refined phylogeny of both angiosperms and gymnosperms to map phylogenetic diversity, clustering and endemism of North American trees in 100-km grid cells, and climate change velocity since Last Glacial Maximum together with postglacial accessibility to recolonization to quantify glacial-interglacial climate variability. We found: (1) Current climate is the dominant factor explaining the overall patterns, with more clustered angiosperm assemblages toward lower temperature, consistent with tropical niche conservatism. (2) Long-term climate stability is associated with higher angiosperm endemism, while higher postglacial accessibility is linked to to more phylogenetic clustering and endemism in gymnosperms. (3) Factors linked to glacial-interglacial climate change have stronger effects on gymnosperms than on angiosperms. These results suggest that paleoclimate legacies supplement current climate in shaping phylogenetic patterns in North American trees, and especially so for gymnosperms. PMID- 27252831 TI - Adcyap1 polymorphism covaries with breeding latitude in a Nearctic migratory songbird, the Wilson's warbler (Cardellina pusilla). AB - Understanding the genetic background of complex behavioral traits, showing multigenic control and extensive environmental effects, is a challenging task. Among such traits, migration is known to show a large additive genetic component. Yet, the identification of specific genes or gene regions explaining phenotypic variance in migratory behavior has received less attention. Migration ultimately depends on seasonal cycles, and polymorphism at phenological candidate genes may underlie variation in timing of migration or other aspects of migratory behavior. In this study of a Nearctic-Neotropical migratory songbird, the Wilson's warbler (Cardellina pusilla), we investigated the association between polymorphism at two phenological candidate genes, Clock and Adcyap1, and two aspects of the migratory phenotype, timing of spring migration through a stopover site and inferred latitude of the breeding destination. The breeding destination of migrating individuals was identified using feather deuterium ratio (delta (2)H), which reliably reflects breeding latitude throughout the species' western breeding range. Ninety-eight percent of the individuals were homozygous at Clock, and the rare heterozygotes did not deviate from homozygous migration phenology. Adcyap1 was highly polymorphic, and allele size was not significantly associated with migration date. However, Adcyap1 allele size significantly positively predicted the inferred breeding latitude of males but not of females. Moreover, we found a strong positive association between inferred breeding latitude and Adcyap1 allele size in long-distance migrating birds from the northern sector of the breeding range (western Canada), while this was not the case in short-distance migrating birds from the southern sector of the breeding range (coastal California). Our findings support previous evidence for a role of Adcyap1 in shaping the avian migratory phenotype, while highlighting that patterns of phenological candidate gene-phenotype associations may be complex, significantly varying between geographically distinct populations and even between the sexes. PMID- 27252832 TI - Structural (UV) and carotenoid-based plumage coloration - signals for parental investment? AB - Parental care increases parental fitness through improved offspring condition and survival but comes at a cost for the caretaker(s). To increase life-time fitness, caring parents are, therefore, expected to adjust their reproductive investment to current environmental conditions and parental capacities. The latter is thought to be signaled via ornamental traits of the bearer. We here investigated whether pre- and/or posthatching investment of blue tit (Cyanistes caeruleus) parents was related to ornamental plumage traits (UV crown coloration and carotenoid-based plumage coloration) expressed by either the individual itself (i.e. "good parent hypothesis") or its partner (i.e. "differential allocation hypothesis"). Our results show that neither prehatching (that is clutch size and offspring begging intensity) nor posthatching parental investment (provisioning rate, offspring body condition at fledging) was related to an individual's UV crown coloration or to that of its partner. Similar observations were made for carotenoid-based plumage coloration, except for a consistent positive relationship between offspring begging intensity and maternal carotenoid-based plumage coloration. This sex-specific pattern likely reflects a maternal effect mediated via maternally derived egg substances, given that the relationship persisted when offspring were cross-fostered. This suggests that females adjust their offspring's phenotype toward own phenotype, which may facilitate in particular mother-offspring co-adaptation. Overall, our results contribute to the current state of evidence that structural or pigment-based plumage coloration of blue tits are inconsistently correlated with central life-history traits. PMID- 27252833 TI - Nuclear introgression without mitochondrial introgression in two turtle species exhibiting sex-specific trophic differentiation. AB - Despite the presence of reproductive barriers between species, interspecific gene introgression has been documented in a range of natural systems. Comparing patterns of genetic introgression in biparental versus matrilineal markers can potentially reveal sex-specific barriers to interspecific gene flow. Hybridization has been documented in the freshwater turtles Graptemys geographica and G. pseudogeographica, whose ranges are largely sympatric. Morphological differentiation between the species is restricted to females, with female G. geographica possessing large heads and jaws compared to the narrow heads of G. pseudogeographica females. If hybrid females are morphologically intermediate, they may be less successful at exploiting parental feeding niches, thereby limiting the introgression of maternally inherited, but not biparental, molecular markers. We paired sequence data with stable isotope analysis and examined sex specific genetic introgression and trophic differentiation in sympatric populations of G. geographica and G. pseudogeographica. We observed introgression from G. pseudogeographica into G. geographica at three nuclear loci, but not at the mitochondrial locus. Analysis of ?(15)N and ?(13)C was consistent with species differences in trophic positioning in females, but not males. These results suggest that ecological divergence in females may reduce the opportunity for gene flow in this system. PMID- 27252834 TI - A trait-based approach reveals the feeding selectivity of a small endangered Mediterranean fish. AB - Functional traits are growing in popularity in modern ecology, but feeding studies remain primarily rooted in a taxonomic-based perspective. However, consumers do not have any reason to select their prey using a taxonomic criterion, and prey assemblages are variable in space and time, which makes taxon based studies assemblage-specific. To illustrate the benefits of the trait-based approach to assessing food choice, we studied the feeding ecology of the endangered freshwater fish Barbus meridionalis. We hypothesized that B. meridionalis is a selective predator which food choice depends on several prey morphological and behavioral traits, and thus, its top-down pressure may lead to changes in the functional composition of in-stream macroinvertebrate communities. Feeding selectivity was inferred by comparing taxonomic and functional composition (13 traits) between ingested and free-living potential prey using the Jacob's electivity index. Our results showed that the fish diet was influenced by 10 of the 13 traits tested. Barbus meridionalis preferred prey with a potential size of 5-10 mm, with a medium-high drift tendency, and that drift during daylight. Potential prey with no body flexibility, conical shape, concealment traits (presence of nets and/or cases, or patterned coloration), and high aggregation tendency had a low predation risk. Similarly, surface swimmers and interstitial taxa were low vulnerable to predation. Feeding selectivity altered the functional composition of the macroinvertebrate communities. Fish absence favored taxa with weak aggregation tendency, weak flexibility, and a relatively large size (10-20 mm of potential size). Besides, predatory invertebrates may increase in fish absence. In conclusion, our study shows that the incorporation of the trait-based approach in diet studies is a promising avenue to improve our mechanistic understanding of predator-prey interactions and to help predict the ecological outcomes of predator invasions and extinctions. PMID- 27252835 TI - Long-term demographic decline and late glacial divergence in a Californian paleoendemic: Sequoiadendron giganteum (giant sequoia). AB - Mediterranean ecosystems comprise a high proportion of endemic taxa whose response to climate change will depend on their evolutionary origins. In the California flora, relatively little attention has been given to the evolutionary history of paleoendemics from a molecular perspective, yet they number among some of the world's most iconic plant species. Here, we address questions of demographic change in Sequoiadendron giganteum (giant sequoia) that is restricted to a narrow belt of groves in the Sierra Nevada Mountains. We ask whether the current distribution is a result of northward colonization since the last glacial maximum (LGM), restriction of a broader range in the recent past (LGM) or independent colonizations in the deeper past. Genetic diversity at eleven microsatellite loci decreased with increasing latitude, but partial regressions suggested this was a function of smaller population sizes in the north. Disjunct populations north of the Kings River were divergent from those south of the Kings River that formed a single cluster in Bayesian assignment tests. Demographic inferences supported a demographic contraction just prior to the LGM as the most likely scenario for the current disjunct range of the species. This contraction appeared to be superimposed upon a long-term decline in giant sequoia over the last 2 million years, associated with increasing aridity due to the Mediterranean climate. Overall, low genetic diversity, together with competition in an environment to which giant sequoia is likely already poorly adapted, will pose major constraints on its success in the face of increasing aridity. PMID- 27252836 TI - Strong paleoclimatic legacies in current plant functional diversity patterns across Europe. AB - Numerous studies indicate that environmental changes during the late Quaternary have elicited long-term disequilibria between species diversity and environment. Despite its importance for ecosystem functioning, the importance of historical environmental conditions as determinants of FD (functional diversity) remains largely unstudied. We quantified the geographic distributions of plant FD (richness and dispersion) across Europe using distribution and functional trait information for 2702 plant species. We then compared the importance of historical and contemporary factors to determine the relevance of past conditions as predictors of current plant FD in Europe. For this, we compared the strength of the relationships between FD with temperature and precipitation stability since the LGM (Last Glacial Maximum), accessibility to LGM refugia, and contemporary environmental conditions (climate, productivity, soil, topography, and land use). Functional richness and dispersion exhibited geographic patterns with strong associations to the environmental history of the region. The effect size of accessibility to LGM refugia and climate stability since the LGM was comparable to that of the contemporary predictors. Both functional richness and dispersion increased with temperature stability since the LGM and accessibility to LGM refugia. Functional richness' geographic pattern was primarily associated with accessibility to LGM refugia growing degree-days, land use heterogeneity, diversity of soil types, and absolute minimum winter temperature. Functional dispersion's geographic pattern was primarily associated with accessibility to LGM refugia growing degree-days and absolute minimum winter temperature. The high explained variance and model support of historical predictors are consistent with the idea that long-term variability in environmental conditions supplements contemporary factors in shaping FD patterns at continental scales. Given the importance of FD for ecosystem functioning, future climate change may elicit not just short-term shifts in ecosystem functioning, but also long-term functional disequilibria. PMID- 27252837 TI - Extinct Beringian wolf morphotype found in the continental U.S. has implications for wolf migration and evolution. AB - Pleistocene diversity was much higher than today, for example there were three distinct wolf morphotypes (dire, gray, Beringian) in North America versus one today (gray). Previous fossil evidence suggested that these three groups overlapped ecologically, but split the landscape geographically. The Natural Trap Cave (NTC) fossil site in Wyoming, USA is an ideally placed late Pleistocene site to study the geographical movement of species from northern to middle North America before, during, and after the last glacial maximum. Until now, it has been unclear what type of wolf was present at NTC. We analyzed morphometrics of three wolf groups (dire, extant North American gray, Alaskan Beringian) to determine which wolves were present at NTC and what this indicates about wolf diversity and migration in Pleistocene North America. Results show NTC wolves group with Alaskan Beringian wolves. This provides the first morphological evidence for Beringian wolves in mid-continental North America. Their location at NTC and their radiocarbon ages suggest that they followed a temporary channel through the glaciers. Results suggest high levels of competition and diversity in Pleistocene North American wolves. The presence of mid-continental Beringian morphotypes adds important data for untangling the history of immigration and evolution of Canis in North America. PMID- 27252838 TI - Erratum: Loss of genetic integrity and biological invasions result from stocking and introductions of Barbus barbus: insights from rivers in England. AB - [This corrects the article DOI: 10.1002/ece3.1906.]. PMID- 27252839 TI - Current concepts in the pathogenesis of chronic thromboembolic pulmonary hypertension. AB - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by fibrotic obstruction of the proximal pulmonary arteries, and it is believed to result from incomplete thrombus resolution after acute pulmonary embolism. While treatment for this condition with surgery and medical therapy has improved outcomes, our understanding of the molecular mechanisms underlying CTEPH is incomplete. Numerous risk factors have been associated with the development of CTEPH, including but not limited to acquired thrombophilias and chronic inflammatory states. A minority of patients with CTEPH have an abnormal fibrin structure that may delay thrombus resolution. Recently, examination of resected scar material in patients with CTEPH has suggested that deficient angiogenesis may play a role in thrombus nonresolution, and there is increasing interest in factors that drive intravascular scar formation. An additional challenge in CTEPH research is understanding the etiology and implications of the small-vessel disease present in many patients. Future work will likely be directed at understanding the pathways important to disease pathogenesis through further examinations of resected tissue material, continued work on animal models, and genomic approaches to identify alterations in gene expression or gene variants that may distinguish CTEPH from other forms of pulmonary hypertension. PMID- 27252840 TI - Echocardiographic parameters of right ventricular function predict mortality in acute respiratory distress syndrome: a pilot study. AB - Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilot study measuring tricuspid annular plane systolic excursion (TAPSE), Tei index, RV-fractional area change (RV-FAC), pulmonary artery systolic pressure (PASP), and septal shift, reevaluated by an independent blinded cardiologist (JK). Thirty-eight patients were included. Patients were divided on the basis of 30-day survival. Thirty-day mortality was 47%. Survivors were younger than nonsurvivors. Survivors had a higher pH, PaO2?FiO2 ratio, and TAPSE. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were lower in survivors. TAPSE has the strongest association with increased 30-day mortality from date of TTE. Accordingly, TAPSE has a strong positive correlation with PaO2?FiO2 ratios, and Tei index has a strong negative correlation with PaO2?FiO2 ratios. Septal shift was associated with lower PaO2?FiO2 ratios. Decrease in TAPSE, increase in Tei index, and septal shift were seen in the severe ARDS group. In multivariate logistic regression models, TAPSE maintained a significant association with mortality independent of age, pH, PaO2?FiO2 ratios, positive end expiratory pressure, PCO2, serum bicarbonate, plateau pressures, driving pressures, APACHE II, SAPS II, and SOFA scores. In conclusion, TAPSE and other TTE parameters should be used as novel predictive indicators for RV dysfunction in ARDS. These parameters can be used as surrogate noninvasive RV hemodynamic measurements to be manipulated to improve mortality in patients with ARDS and contributory RV dysfunction. PMID- 27252841 TI - Sildenafil in heart failure with reactive pulmonary hypertension (Sildenafil HF) clinical trial (rationale and design). AB - In this article, we present the rationale and design of the Sildenafil HF trial (ClinicalTrials.gov identifier: NCT02304705). We will randomize patients with heart failure and reactive pulmonary hypertension (pulmonary capillary wedge pressure > 15 mmHg, pulmonary vascular resistance > 3 Wood units) into two groups: the treatment group receiving sildenafil 20 mg 3 times a day and a matching placebo group. The duration of intervention will be 3 months. The primary outcome is 6-minute walk distance. Key features of this trial include (1) that reactive pulmonary hypertension is an inclusion criterion, (2) that patients will be enrolled regardless of left ventricular ejection fraction, and (3) that clinical stability in the 3 months preceding enrollment is not required. PMID- 27252842 TI - Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. AB - Endothelin receptor antagonists (ERAs) have been shown to improve the prognosis of patients with pulmonary arterial hypertension (PAH). However, the effect of the oral dual ERA bosentan on peripheral endothelial dysfunction (PED), as assessed by flow-mediated vasodilation (FMD), in patients with pulmonary hypertension is not well characterized. We investigated the effect of bosentan on PED in patients with PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A total of 18 patients with PAH and 8 with CTEPH were treated with bosentan. All patients underwent FMD assessment before and after 3 months of bosentan treatment. Whereas FMD increased from 6.01% +/- 2.42% at baseline to 8.07% +/- 3.18% after 3 months (P < 0.0001) in patients with PAH, those with CTEPH showed no change in FMD after bosentan therapy. In addition, FMD at baseline showed no correlation with pulmonary vascular resistance (r = 0.09) or plasma brain natriuretic peptide levels (r = -0.23) in patients with PAH. Bosentan treatment ameliorated PED in patients with PAH but not in those with inoperable CTEPH. In addition, FMD did not correlate with PAH severity. PMID- 27252843 TI - Severity of pulmonary hypertension and obesity are not associated with worse functional outcomes after pulmonary thromboendarterectomy. AB - Predictors of functional outcomes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary thromboendarterectomy (PTE) are important to identify preoperatively. We hypothesized that baseline severity of pulmonary hypertension and obesity would not be associated with 6-month functional outcomes after PTE. Clinical and hemodynamic data were collected on consecutive patients undergoing PTE from 2008 to 2014. Patients were stratified according to baseline pulmonary vascular resistance (PVR) and body mass index (BMI). Six-minute walk distance (6MWD), New York Heart Association functional class (FC), and echocardiography were assessed in each group at baseline and 6 months after PTE. Regression analyses were performed to evaluate for associations between functional outcomes and baseline PVR and BMI. Forty-two patients underwent PTE and had 6-month follow up data. In comparisons of patients with high and low baseline PVR, the baseline characteristics, distribution of disease, 6MWD, and FC were similar. Postoperative hemodynamics for both groups were similar. At 6 months, both groups achieved improvements in FC, and there were no between-group differences in the change in 6MWD or FC. In comparisons of obese and nonobese patients, perioperative and FC improvement were similar; however, obese patients achieved a greater improvement in 6MWD than nonobese patients (P = 0.04). In conclusion, our data suggest that baseline severity of CTEPH and obesity were not associated with worse functional outcome. Further studies are needed to confirm these results, as these findings could have implications for patient selection for PTE. PMID- 27252844 TI - Diagnosis of pulmonary hypertension from magnetic resonance imaging-based computational models and decision tree analysis. AB - Accurately identifying patients with pulmonary hypertension (PH) using noninvasive methods is challenging, and right heart catheterization (RHC) is the gold standard. Magnetic resonance imaging (MRI) has been proposed as an alternative to echocardiography and RHC in the assessment of cardiac function and pulmonary hemodynamics in patients with suspected PH. The aim of this study was to assess whether machine learning using computational modeling techniques and image-based metrics of PH can improve the diagnostic accuracy of MRI in PH. Seventy-two patients with suspected PH attending a referral center underwent RHC and MRI within 48 hours. Fifty-seven patients were diagnosed with PH, and 15 had no PH. A number of functional and structural cardiac and cardiovascular markers derived from 2 mathematical models and also solely from MRI of the main pulmonary artery and heart were integrated into a classification algorithm to investigate the diagnostic utility of the combination of the individual markers. A physiological marker based on the quantification of wave reflection in the pulmonary artery was shown to perform best individually, but optimal diagnostic performance was found by the combination of several image-based markers. Classifier results, validated using leave-one-out cross validation, demonstrated that combining computation-derived metrics reflecting hemodynamic changes in the pulmonary vasculature with measurement of right ventricular morphology and function, in a decision support algorithm, provides a method to noninvasively diagnose PH with high accuracy (92%). The high diagnostic accuracy of these MRI based model parameters may reduce the need for RHC in patients with suspected PH. PMID- 27252845 TI - Socioeconomic status affects pulmonary hypertension disease severity at time of first evaluation. AB - A low socioeconomic status (SES) has been linked to disproportionate access to health care in many diseases, leading to worse disease severity at initial presentation. There is a paucity of these data in the pulmonary hypertension (PHTN) population. We studied the association of SES, as measured by zip code based median annual household income, with World Health Organization functional class (WHO-FC) at time of first evaluation in PHTN patients. All patients evaluated at our center with a right heart catheterization revealing a mean pulmonary artery pressure of >=25 mmHg within 12 months of initial evaluation were considered for the study. Demographics, WHO-FC, and zip codes were obtained from retrospective chart analysis. The 2010 US census was used to obtain zip code based annual median income. The income groups were divided into quartiles. Patients were categorized by their WHO-FC and zip code-derived median income. Similar analyses were conducted for pulmonary arterial hypertension (PAH) patients. Survival was estimated with the Kaplan-Meier method. Data were analyzed in SAS, and P < 0.05 was considered significant. There were 228 PHTN patients (70 [30.7%] male, 158 [69.3%] female). As median income decreased, the FC at presentation increased, signifying higher disease severity (Spearman correlation: r = -0.161, P < 0.0515). This association between median income groups and WHO-FC at initial evaluation was significant (chi(2) test: P < 0.0168). There were 116 PAH patients (32 [27.6%] male, 84 [72.4%] female). There was again a negative relationship between income and initial FC (Spearman correlation: r = -0.0307, P < 0.0007). A lower SES was associated with worse disease, as measured by WHO-FC. PMID- 27252846 TI - Reactive oxygen species-associated molecular signature predicts survival in patients with sepsis. AB - Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)-associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies. PMID- 27252847 TI - Proline-rich tyrosine kinase 2 downregulates peroxisome proliferator-activated receptor gamma to promote hypoxia-induced pulmonary artery smooth muscle cell proliferation. AB - Hypoxia stimulates pulmonary hypertension (PH), in part by increasing the proliferation of human pulmonary artery smooth muscle cells (HPASMCs) via sustained activation of mitogen-activated protein kinase, extracellular signal regulated kinases 1 and 2 (ERK 1/2), and nuclear factor-kappa B (NF-kappaB); elevated expression of NADPH oxidase 4 (Nox4); and downregulation of peroxisome proliferator-activated receptor gamma (PPARgamma) levels. However, the upstream mediators that control these responses remain largely unknown. We hypothesized that proline-rich tyrosine kinase 2 (Pyk2) plays a critical role in the mechanism of hypoxia-induced HPASMC proliferation. To test this hypothesis, HPASMCs were exposed to normoxia or hypoxia (1% O2) for 72 hours. Hypoxia activated Pyk2 (detected as Tyr402 phosphorylation), and inhibition of Pyk2 with small interfering RNA (siRNA) or tyrphostin A9 attenuated hypoxia-induced HPASMC proliferation. Pyk2 inhibition attenuated ERK 1/2 activation as early as 24 hours after the onset of hypoxia, suggesting a proximal role for Pyk2 in this response. Pyk2 inhibition also attenuated hypoxia-induced NF-kappaB activation, reduced HPASMC PPARgamma messenger RNA levels and activity, and increased NF-kappaB mediated Nox4 levels. The siRNA-mediated PPARgamma knockdown enhanced Pyk2 activation, whereas PPARgamma overexpression reduced Pyk2 activation in HPASMCs, confirming a reciprocal relationship between Pyk2 and PPARgamma. Pyk2 depletion also attenuated hypoxia-induced NF-kappaB p65 activation and reduced PPARgamma protein levels in human pulmonary artery endothelial cells. These in vitro findings suggest that Pyk2 plays a central role in the proliferative phenotype of pulmonary vascular wall cells under hypoxic conditions. Coupled with recent reports that hypoxia-induced PH is attenuated in Pyk2 knockout mice, these findings suggest that Pyk2 may represent a novel therapeutic target in PH. PMID- 27252848 TI - Antagonism of the thromboxane-prostanoid receptor is cardioprotective against right ventricular pressure overload. AB - Right ventricular (RV) failure is the primary cause of death in pulmonary arterial hypertension (PAH) and is a significant cause of morbidity and mortality in other forms of pulmonary hypertension. There are no approved therapies directed at preserving RV function. F-series and E-series isoprostanes are increased in heart failure and PAH, correlate to the severity of disease, and can signal through the thromboxane-prostanoid (TP) receptor, with effects from vasoconstriction to fibrosis. The goal of these studies was to determine whether blockade of the TP receptor with the antagonist CPI211 was beneficial therapeutically in PAH-induced RV dysfunction. Mice with RV dysfunction due to pressure overload by pulmonary artery banding (PAB) were given vehicle or CPI211. Two weeks after PAB, CPI211-treated mice were protected from fibrosis with pressure overload. Gene expression arrays and immunoblotting, quantitative histology and morphometry, and flow cytometric analysis were used to determine the mechanism of CPI211 protection. TP receptor inhibition caused a near normalization of fibrotic area, prevented cellular hypertrophy while allowing increased RV mass, increased expression of antifibrotic thrombospondin-4, and blocked induction of the profibrotic transforming growth factor beta (TGF-beta) pathway. A thromboxane synthase inhibitor or low-dose aspirin failed to replicate these results, which suggests that a ligand other than thromboxane mediates fibrosis through the TP receptor after pressure overload. This study suggests that TP receptor antagonism may improve RV adaptation in situations of pressure overload by decreasing fibrosis and TGF-beta signaling. PMID- 27252849 TI - Plasma 12- and 15-hydroxyeicosanoids are predictors of survival in pulmonary arterial hypertension. AB - This study aimed to characterize alterations in select eicosanoids in experimental and human pulmonary arterial hypertension (PAH) and to assess their potential utility as predictors of outcome. Using liquid chromatography-mass spectrometry, we performed targeted lipidomic analyses of the lungs and right ventricles (RVs) of chronically hypoxic rats and plasma of consecutive PAH patients and healthy controls. In rat lungs, chronic hypoxia was associated with significantly decreased lung prostacyclin (PGI2)/thromboxane B2 (TXB2) ratio and elevated lung 8-hydroxyeicosanoid (HETE) acid concentrations. RV eicosanoids did not exhibit any changes with chronic hypoxia. PAH treatment-naive patients had significantly increased plasma concentrations of TXB2 and 5-, 8-, 12-, and 15 HETE. The PGI2/TXB2 ratio was lower in PAH patients than in controls, especially in the treatment-naive cohort (median: 2.1, 0.3, and 1.3 in controls, treatment naive, and treated patients, respectively, P = 0.001). Survival was significantly worse in PAH patients with 12-HETEhigh (>=57 pg/mL) and 15-HETEhigh (>=256 pg/mL) in unadjusted and adjusted analyses (hazard ratio [HR]: 2.8 [95% confidence interval (CI): 1.1-7.3], P = 0.04 and HR: 4.3 [95% CI: 1.6-11.8], P = 0.004, respectively; adjustment was performed with the REVEAL [Registry to Evaluate Early and Long-Term PAH Disease Management] risk score). We demonstrate significant alterations in eicosanoid pathways in experimental and human PAH. We found that 12- and 15-HETE were independent predictors of survival in human PAH, even after adjusting for the REVEAL score, suggesting their potential role as novel biomarkers. PMID- 27252850 TI - Nonmuscle myosin light chain kinase activity modulates radiation-induced lung injury. AB - Radiotherapy as a primary treatment for thoracic malignancies induces deleterious effects, such as acute or subacute radiation-induced lung injury (RILI). Although the molecular etiology of RILI is controversial and likely multifactorial, a potentially important cellular target is the lung endothelial cytoskeleton that regulates paracellular gap formation and the influx of macromolecules and fluid to the alveolar space. Here we investigate the central role of a key endothelial cytoskeletal regulatory protein, the nonmuscle isoform of myosin light chain kinase (nmMLCK), in an established murine RILI model. Our results indicate that thoracic irradiation significantly augmented nmMLCK protein expression and enzymatic activity in murine lungs. Furthermore, genetically engineered mice harboring a deletion of the nmMLCK gene (nmMLCK(-/-) mice) exhibited protection from RILI, as assessed by attenuated vascular leakage and leukocyte infiltration. In addition, irradiated wild-type mice treated with two distinct MLCK enzymatic inhibitors, ML-7 and PIK (peptide inhibitor of kinase), also demonstrated attenuated RILI. Taken together, these data suggests a key role for nmMLCK in vascular barrier regulation in RILI and warrants further examination of RILI strategies that target nmMLCK. PMID- 27252851 TI - Pulmonary artery denervation for treatment of a patient with pulmonary hypertension secondary to left heart disease. AB - Pulmonary hypertension (PH) predicts poor outcome in patients with left heart disease. A 62-year-old man was referred for heart failure associated with ischemic cardiomyopathy. He received a diagnosis of combined postcapillary and precapillary PH secondary to left heart disease on the basis of hemodynamic parameters. After the pulmonary artery denervation procedure was performed, hemodynamic parameters were markedly improved, which resulted in a significant increase in functional capacity. PMID- 27252852 TI - Pulmonary arterial hypertension in primary amyloidosis. AB - Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID- 27252853 TI - The basal bodies of Chlamydomonas reinhardtii. AB - The unicellular green alga, Chlamydomonas reinhardtii, is a biflagellated cell that can swim or glide. C. reinhardtii cells are amenable to genetic, biochemical, proteomic, and microscopic analysis of its basal bodies. The basal bodies contain triplet microtubules and a well-ordered transition zone. Both the mother and daughter basal bodies assemble flagella. Many of the proteins found in other basal body-containing organisms are present in the Chlamydomonas genome, and mutants in these genes affect the assembly of basal bodies. Electron microscopic analysis shows that basal body duplication is site-specific and this may be important for the proper duplication and spatial organization of these organelles. Chlamydomonas is an excellent model for the study of basal bodies as well as the transition zone. PMID- 27252854 TI - Acute mountain sickness among tourists visiting the high-altitude city of Lhasa at 3658 m above sea level: a cross-sectional study. AB - BACKGROUND: Traveling to Tibet implies a risk for developing acute mountain sickness (AMS), and the size of this problem is likely increasing due to the rising number of tourists. No previous study on AMS has been conducted among the general tourist population in Tibet. Thus, the aim of this study was to estimate the prevalence and determinants of AMS in a large tourist population visiting Lhasa. METHODS: A sample of 2385 tourists was recruited from seven randomly selected hotels in Lhasa between June and October 2010. Within three days of their first arrival, the participants filled in a questionnaire based on the Lake Louise Scoring System (LLSS) about AMS-related symptoms and potential contributing factors. AMS was defined as the presence of headache and a cumulative Lake Louise Score >=4. After estimating the prevalence of AMS, a Log Binomial Model was applied to analyse the relationship between AMS and selected risk factors. RESULTS: The prevalence of AMS was 36.7 % (95 % CI: 34.6-38.7 %) and was not dependent on tourists' country of origin. Among the participants who developed AMS, 47.6 % reported that they experienced symptoms within the first 12 h after arriving in Lhasa, and 79.0 % reported that they had to reduce their activity level. A poor or average health condition (adjusted PR 1.63, 95 % CI 1.38-1.93), an age below 55 years (adjusted PR 1.29, 95 % CI 1.04-1.60), a rapid ascent to Lhasa (adjusted PR 1.17, 95 % CI 1.02-1.34) were independent AMS risk factors, while smoking (adjusted PR 0.75, 95 % CI 0.59-0.96) and pre-exposure to high altitude (adjusted PR 0.71, 95 % CI 0.60-0.84) reduced the risk of AMS. CONCLUSIONS: AMS is commonly experienced by tourists visiting Lhasa Tibet, and often affects their activities. The tourists' country of origin did not seem to affect their risk of AMS, and their age was inversely related to AMS. Subjects planning to visit a high-altitude area should be prepared for experiencing AMS related problems, and consider preventive measures such as pre-exposure or a gradual ascent to high altitudes. PMID- 27252855 TI - Identification of functional metabolic biomarkers from lung cancer patient serum using PEP technology. AB - BACKGROUND: Reprogrammed metabolism is a new hallmark of cancer. In many types of cancer, most of the genes in the glycolytic pathway are overexpressed, reflecting an essential shift of metabolism during cancer development. The reprogrammed metabolism contributes to cancer development in multiple ways, from supplying the elevated energy requirement to creating a microenvironment suitable for tumor growth and suppressing the human immune surveillance system. METHOD: In this study, a functional proteomics top-down approach was used to systematically monitor metabolic enzyme activities in resolved serum proteins produced by a modified 2-D gel separation and subsequent Protein Elution Plate, a method collectively called PEP. RESULTS: We found that the enrichment of low abundance proteins with a bead based product called AlbuVoidTM(,) is important to increase the number of observable features and to increase the level of signal achievable from the assay used. From our methods, significant metabolic enzyme activities were detected in both normal and lung cancer patient sera in many fractions after the elution of the 2-D gel separated proteins to the Protein Elution Plate (PEP). Eighteen fractions with the most dramatic metabolic enzyme activity difference between the normal and lung cancer patient sera were submitted for mass spectrometry protein identification. Proteins from the glycolytic metabolic pathway, such as GAPDH along with other proteins not previously annotated to the glycolytic pathway were identified. Further verification with commercially purified GAPDH showed that the addition of purified GAPDH to the metabolic enzyme assay system employed enhanced the enzyme activity, demonstrating that proteins identified from the PEP technology and mass spectrometry could be further verified with biological assay. CONCLUSION: This study identified several potential functional enzyme biomarkers from lung cancer patient serum, it provides an alternative and complementary approach to sequence annotation for the discovery of biomarkers in human diseases. PMID- 27252856 TI - Flexible characterization of animal movement pattern using net squared displacement and a latent state model. AB - BACKGROUND: Characterizing the movement patterns of animals is an important step in understanding their ecology. Various methods have been developed for classifying animal movement at both coarse (e.g., migratory vs. sedentary behavior) and fine (e.g., resting vs. foraging) scales. A popular approach for classifying movements at coarse resolutions involves fitting time series of net squared displacement (NSD) to models representing different conceptualizations of coarse movement strategies (i.e., migration, nomadism, sedentarism, etc.). However, the performance of this method in classifying actual (as opposed to simulated) animal movements has been mixed. Here, we develop a more flexible method that uses the same NSD input, but relies on an underlying discrete latent state model. Using simulated data, we first assess how well patterns in the number of transitions between modes of movement and the duration of time spent in a mode classify movement strategies. We then apply our approach to elucidate variability in the movement strategies of eight giant tortoises (Chelonoidis sp.) using a multi-year (2009-2014) GPS dataset from three different Galapagos Islands. RESULTS: With respect to patterns of time spent and the number of transitions between modes, our approach out-performed previous efforts to distinguish among migration, dispersal, and sedentary behavior. We documented marked inter-individual variation in giant tortoise movement strategies, with behaviors indicating migration, dispersal, nomadism and sedentarism, as well as hybrid behaviors such as "exploratory residence". CONCLUSIONS: Distilling complex animal movement into discrete modes remains a fundamental challenge in movement ecology, a problem made more complex by the ever-longer duration, ever-finer resolution, and gap-ridden trajectories recorded by GPS devices. By clustering into modes, we derived information on the time spent within one mode and the number of transitions between modes which enabled finer differentiation of movement strategies over previous methods. Ultimately, the techniques developed here address limitations of previous approaches and provide greater insights with respect to characterization of movement strategies across scales by more fully utilizing long-term GPS telemetry datasets. PMID- 27252857 TI - Difficulties in emotion regulation in patients with eating disorders. AB - BACKGROUND: A defining characteristic of eating disorders (EDs) is difficulty with emotion regulation (ER). Previous research indicates that ED subtypes demonstrate differing ER difficulties. Specifically, individuals with Anorexia Nervosa (AN) or Bulimia Nervosa (BN) show greater impairment in their ability to regulate emotions in areas such as achieving goals while upset, reacting impulsively to distress, and effectively using coping strategies, as compared to those with Binge Eating Disorder (BED). However, limited research includes the diagnostic category of Eating Disorder, Not Otherwise Specified (EDNOS). The aim of this study was to better understand ER difficulties for all ED diagnoses, especially EDNOS. It was hypothesized that patients with EDs will demonstrate similar ER difficulties as psychiatric patients without EDs and that patients with EDNOS will be similar in their total level of ER difficulties but will differ in their specific types of difficulties in ER as compared to patients with other EDs. METHODS: Participants included 404 adults presenting to an inpatient psychiatric hospital. Psychiatric diagnoses, including EDs, were determined using the Structured Clinical Interview for DSM Disorders. Differences in specific and overall difficulties with ER were examined across psychiatric patients using the multidimensional Difficulties in Emotion Regulation Scale. RESULTS: Results of this study indicate that individuals with EDs have greater ER difficulties in most domains of ER and that those with BED and EDNOS demonstrate the most significant differences in ER as compared to psychiatric patients without EDs. Additionally, it was found that ED subtypes typically did not differ in terms of specific difficulties in ER. One exception emerged indicating that individuals with BED demonstrated significantly greater difficulty on the Limited Access to Emotion Regulation Strategies subscale as compared to those with EDNOS. CONCLUSIONS: Researchers were able to clarify difficulties in ER across ED diagnoses. Results highlight the importance of providing ER skills training for patients with EDs, particularly those with BED and EDNOS, and give insight into the specific areas of ER that may be important for these patients to focus on throughout recovery. PMID- 27252858 TI - A case of adrenal Cushing's syndrome with bilateral adrenal masses. AB - A functional lesion in corticotrophin (ACTH)-independent Cushing's syndrome is difficult to distinguish from lesions of bilateral adrenal masses. Methods for distinguishing these lesions include adrenal venous sampling and (131)I-6beta iodomethyl-19-norcholesterol ((131)I-NP-59) scintigraphy. We present a case of a 29-year-old Han Chinese female patient with a history of hypercholesterolaemia and polycystic ovary syndrome. She presented with a 6month history of an 8kg body weight gain and gradual rounding of the face. Serial examinations revealed loss of circadian rhythm of cortisol, elevated urinary free-cortisol level and undetectable ACTH level (<5pg/mL). No suppression was observed in both the low- and high-dose dexamethasone suppression tests. Adrenal computed tomography revealed bilateral adrenal masses. Adrenal venous sampling was performed, and the right-to-left lateralisation ratio was 14.29. The finding from adrenal scintigraphy with NP-59 was consistent with right adrenal adenoma. The patient underwent laparoscopic right adrenalectomy, and the pathology report showed adrenocortical adenoma. Her postoperative cortisol level was 3.2MUg/dL, and her Cushingoid appearance improved. In sum, both adrenal venous sampling and (131)I NP-59 scintigraphy are good diagnostic methods for Cushing's syndrome presenting with bilateral adrenal masses. LEARNING POINTS: The clinical presentation of Cushing' syndrome includes symptoms and signs of fat redistribution and protein wasting features.The diagnosis of patients with ACTH-independent Cushing's syndrome with bilateral adrenal masses is challenging for localisation of the lesion.Both adrenal venous sampling and (131)I-NP-59 scintigraphy are good methods to use in these patients with Cushing's syndrome presenting with bilateral adrenal masses. PMID- 27252859 TI - Diabetic foot complicated by vertebral osteomyelitis and epidural abscess. AB - Vertebral osteomyelitis (or spondylodiscitis) is steadily increasing in Western countries and often results from hematogenous seeding, direct inoculation during spinal surgery, or contiguous spread from an infection in the adjacent soft tissue. We present the case of a 67-year-old white patient with type 2 diabetes who went to Hospital for high fever, back pain, and worsening of known infected ulcers in the left foot. Despite intravenous antibiotic treatment and surgical debridement of the foot infection, high fever and lower back pain continued. Bone biopsy and two consecutive blood cultures were positive for Staphylococcus aureus. A spinal magnetic resonance imaging (MRI) was performed, revealing serious osteomyelitis in L4 and L5 complicated by an epidural abscess. Contiguous or other distant focuses of infection were not identified. In this case, diabetic foot could be considered as a primary distant focus for vertebral osteomyelitis. Clinicians should consider vertebral osteomyelitis as a 'possible' diagnosis in patients with type 2 diabetes complicated by foot infection that is associated with fever and lower back pain. LEARNING POINTS: Vertebral osteomyelitis is increasing in Western countries, especially in patients with type 2 diabetes.The primary focus of infection is the genitourinary tract followed by skin, soft tissue, endocarditis, bursitis, septic arthritis, and intravascular access.Diabetic foot could be a rare primary focus of infection for vertebral osteomyelitis, and, however, vertebral osteomyelitis could be a serious, albeit rare, complication of diabetic foot.Clinicians should keep in mind the many potential complications of diabetic foot ulcerations and consider vertebral osteomyelitis as a "possible" diagnosis in patients with type 2 diabetes and foot ulcers associated with nonspecific symptoms such as lower back pain.Early diagnosis and correct management of vertebral osteomyelitis are crucial to improve clinical outcomes. PMID- 27252860 TI - Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults. AB - Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol. LEARNING POINTS: Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA).Sitagliptin administration in patients with LADA might prolong the insulin-free period.Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease. PMID- 27252861 TI - Is radioiodine administration in patients with papillary thyroid multifocal microcarcinoma unnecessary? AB - Radioiodine (RAI) has played a crucial role in differentiated thyroid cancer treatment for more than 60years. However, the use of RAI administration in patients with papillary thyroid microcarcinoma (even multifocal) is now being widely discussed and often not recommended. In accordance with European consensus, and contrary to the American Thyroid Association (ATA) guidelines, we recently performed RAI thyroid remnant ablation in a patient with differentiated papillary multifocal microcarcinoma. The post-therapeutic whole-body scan and SPECT/CT revealed the real and unexpected extent of disease, with metastases to upper mediastinal lymph nodes. This finding led to the patient's upstaging from stage I to stage IVa according to the American Joint Committee on Cancer/International Union Against Cancer criteria. LEARNING POINTS: (131)I is a combined beta-gamma emitter, thus allowing not only residual thyroid tissue ablation but also metastatic tissue imaging.RAI remnant ablation omission also means post-treatment whole-body scan omission, which may lead to disease underestimation, due to incorrect nodal and metastatic staging.RAI should be considered also in "low-risk" patients, especially when the lymph node involvement is not reliably documented.Lower administered RAI activity (30mCi, 1.1GBq) may be a workable compromise in low-risk patients, not indicated for RAI remnant ablation according to ATA guidelines. PMID- 27252862 TI - Thyroid lipomatosis in a 36-year-old patient with rheumatoid arthritis and a kidney transplant. AB - Thyroid lipomatosis is a rare disease, as a total of 20 cases have been described in the literature. It is characterized by diffuse infiltration of the stroma by mature adipose tissue and by progressive growth that produces different degrees of compressive symptoms. Our aim is to present the case of a 36-year-old woman who consulted because of dyspnea caused by a multinodular goiter. She underwent surgery with the presumptive diagnosis of a malignant neoplasia, but the pathological examination of the surgical specimen established the diagnosis of thyroid lipomatosis. LEARNING POINTS: Thyroid lipomatosis is a rare, benign disease characterized by diffuse infiltration of the stroma by mature adipose tissue.The pathophysiology of diffuse proliferation of adipose tissue in the thyroid gland is unclear.Thyroid lipomatosis is clinically manifested by a progressive enlargement of the thyroid that can involve the airway and/or upper gastrointestinal tract, producing dyspnea, dysphagia, and changes in the voice.Given the rapid growth of the lesion, the two main differential diagnoses are anaplastic carcinoma and thyroid lymphoma.Imaging studies may suggest a differential diagnosis, but a definitive diagnosis generally requires histopathological confirmation after a thyroidectomy. PMID- 27252863 TI - The McKittrick-Wheelock syndrome: a rare cause of curable diabetes. AB - McKittrick-Wheelock syndrome (MWS) is a rare consequence of severe dehydration and electrolyte depletion due to mucinous diarrhoea secondary to a rectosigmoid villous adenoma. Reported cases of MWS commonly describe hypersecretion of mucinous diarrhoea in association with dehydration, hypokalaemia, hyponatraemia, hypochloraemia and pre-renal azotemia. Hyperglycaemia and diabetes are rarely reported manifestations of MWS. Herein we describe the case of a 59-year-old woman who presented with new-onset diabetes and severe electrolyte derangement due to a giant rectal villous adenoma. Subsequent endoscopic resection of the tumour cured her diabetes and normalised electrolytes. This case describes a rare cause of 'curable diabetes' and indicates hyperaldosteronism and/or whole-body potassium stores as important regulators of insulin secretion and glucose homeostasis. LEARNING POINTS: McKittrick-Wheelock syndrome (MWS) is typically characterised by the triad of pre-renal failure, electrolyte derangement and chronic diarrhoea resulting from a secretory colonic neoplasm.Hyperglycaemia and new-onset diabetes are rare clinical manifestations of MWS.Hyperaldosteronism and/or hypokalaemia may worsen glucose tolerance in MWS.Aggressive replacement of fluid and electrolytes is the mainstay of acute management, with definitive treatment and complete reversal of the metabolic abnormalities being achieved by endoscopic or surgical resection of the neoplasm. PMID- 27252864 TI - Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing's syndrome. AB - Avascular necrosis (AVN) is a rare presenting feature of endogenous hypercortisolism. If left untreated, complete collapse of the femoral head may ensue, necessitating hip replacement in up to 70% of patients. The majority of the described patients with AVN due to endogenous hypercortisolaemia required surgical intervention. A 36-year-old female, investigated for right leg pain, reported rapid weight gain, bruising and secondary amenorrhoea. She had abdominal adiposity with violaceous striae, facial plethora and hirsutism, atrophic skin, ecchymosis and proximal myopathy. Investigations confirmed cortisol excess (cortisol following low-dose 48h dexamethasone suppression test 807nmol/L; 24h urinary free cortisol 1443nmol (normal<290nmol)). Adrenocorticotrophic hormone (ACTH) was <5.0pg/mL. CT demonstrated subtle left adrenal gland hypertrophy. Hypercortisolaemia persisted after left adrenalectomy. Histology revealed primary pigmented micronodular adrenal disease. Post-operatively, right leg pain worsened and left leg pain developed, affecting mobility. MRI showed bilateral femoral head AVN. She underwent right adrenalectomy and steroid replacement was commenced. Four months after surgery, leg pain had resolved and mobility was normal. Repeat MRI showed marked improvement of radiological abnormalities in both femoral heads, consistent with spontaneous healing of AVN. We report a case of Cushing's syndrome due to primary pigmented nodular adrenocortical disease, presenting with symptomatic AVN of both hips. This was managed conservatively from an orthopaedic perspective. Following cure of hypercortisolaemia, the patient experienced excellent recovery and remains symptom free 4 years after adrenalectomy. This is the first report of a favourable outcome over long-term follow-up of a patient with bilateral AVN of the hip, which reversed with treatment of endogenous hypercortisolaemia. LEARNING POINTS: AVN of femoral head can be a presenting feature of hypercortisolism, both endogenous and exogenous.Rarely, treatment of hypercortisolaemia can reverse AVN without the need for orthopaedic intervention.Primary pigmented nodular adrenal disease is a rare cause of ACTH-independent Cushing's syndrome. PMID- 27252865 TI - Turner syndrome: don't forget the vulva. AB - Turner syndrome (TS) has been linked to a number of autoimmune conditions, including lichen sclerosus (LS), at an estimated prevalence of 17%. LS is a known precursor to vulvar cancer. We present a case of vulvar cancer in a 44-year-old woman, who had previously complained of pruritus in the area, a known symptom of LS. Histology confirmed a squamous cell carcinoma with underlying LS. Vulvar assessment for the presence of LS should be undertaken regularly as part of the routine assessments proposed for adult TS women. If LS is identified, then the patient should be warned of the increased risk of vulvar cancer progression and should be monitored closely for signs of the condition. LEARNING POINTS: Patients with TS are at increased risk of developing LS.LS is a known precursor to vulvar cancer.TS women with LS may be at risk of developing vulvar cancer and should be offered annual vulvar screening and also be aware of signs and symptoms of early vulvar cancer. PMID- 27252866 TI - A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing's syndrome. AB - We present a case of a young female patient with a rare cause of relapsing and remitting Cushing's syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing's syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms 'relapsing and remitting' in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing's syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non smoking. LEARNING POINTS: Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing's syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient's symptoms is noteworthy, given the paucity of this finding among other published cases. PMID- 27252867 TI - Pancreas-protective effect of rituximab for acute-onset type 1 diabetes in the honeymoon period: a case report. AB - A randomized controlled study of rituximab demonstrated that the drug protects pancreatic function in patients with acute-onset type 1 diabetes mellitus (AOT1DM). However, the mechanism of this protective effect is poorly understood. We examined the effects of rituximab in two patients with AOT1DM in the honeymoon period and the mechanism of these effects. Case 1 was a 40-year-old man and Case 2 was a 45-year-old man, both diagnosed with AOT1DM. Various tests indicated intact capacity for endogenous insulin secretion and that they were in the honeymoon phase of AOT1DM. Treatment with rituximab protected against pancreatic beta-cell damage and maintained somewhat the endogenous insulin secretion. In Case 2, HbA1c level was maintained below 6.5% up to 24 months after treatment. However, in Case 1, the patient showed a gradual increase in HbA1c level starting around 9 months but fell at 12 months to >9.0% and required an insulin dose about twice greater than that of Case 2. High spleen tyrosine kinase (Syk) levels were recorded in the two patients before rituximab administration and after the treatment, the levels were further increased in Case 1, but decreased in Case 2. Both patients require continuous careful follow-up for glycemic control, insulin secretion capacity, and adverse reactions in the future. Although the clinical relevance of high Syk levels in AOT1DM patients remains unclear, the difference in the change in Syk level between the two patients may explain the different clinical courses. LEARNING POINTS: We described the pancreas-protective effect of rituximab in two patients with acute-onset type 1 diabetes mellitus in the honeymoon period and investigated the possible mechanism of action.The present study demonstrated that treatment with rituximab maintained endogenous insulin secretion capacity for 2 years in the two patients.The phosphorylated-spleen tyrosine kinase (p-Syk) data suggest that the differences in HbA1c level and the required insulin dose between the two patients could be due to reactivation or nonreactivation of beta-cells. PMID- 27252868 TI - Primary ovarian insufficiency: different approaches in three cases and a review of literature. AB - Primary ovarian insufficiency (POI) is the condition of intermittent or permanent gonadal insufficiency that occurs in women before the age of 40. We describe three cases of POI referred to the outpatient endocrinology clinic of a university hospital. The three patients met diagnostic criteria for POI and were managed by specific approaches tailored to individualized goals. In the first case, the main concern was fertility and the reproductive prognosis. The second patient was a carrier of a common genetic cause of POI: premutation of the FMR1 gene. The third case was a patient diagnosed with a POI and established osteoporosis, a common complication of estrogen deprivation. This study reports the treatment and follow-up of these cases, with an emphasis on relevant aspects of individualized management, alongside a brief literature review. LEARNING POINTS: A diagnosis of POI should be considered in patients presenting with amenorrhea or irregular menses and high serum follicle-stimulating hormone (FSH) levels before age 40 years.Patients with POI without an established cause, especially in familial cases, should be tested for FMR1 mutations.Estrogen/progestin replacement therapy is indicated since diagnosis until at least the estimated age of menopause, and is the cornerstone for maintaining the good health of breast and urogenital tract and for primary or secondary osteoporosis prevention in POI.Fertility should be managed through an individualized approach based on patient possibilities, such as egg or embryo donation and ovarian cryopreservation; pregnancy can occur spontaneously in a minority of cases.Women with POI should be carefully monitored for cardiovascular risk factors. PMID- 27252869 TI - Article 1: Supervision, Performance Assessment, and Recognition Strategy (SPARS) a multipronged intervention strategy for strengthening medicines management in Uganda: method presentation and facility performance at baseline. AB - BACKGROUND: Uganda introduced a multipronged intervention, the supervision, performance assessment, and recognition strategy (SPARS), to improve medicines management (MM) in public and not-for-profit health facilities. This paper, the first in a series, describes the SPARS intervention and reports on the MM situation in Uganda before SPARS (baseline). METHODS: To build MM capacity at health facilities, health workers were trained as MM supervisors to visit health facilities, assess MM performance, and use the findings to provide support and standardize MM practices. Performance is assessed based on 25 MM indicators covering five domains: dispensing quality (7 indicators), prescribing quality (5), stock management (4), storage management (5) and ordering and reporting (4). From the end of 2010 to 2013, MM supervisors assessed baseline MM performance of 1384 government (85 %) and private not-for-profit facilities at all levels of care in about half of Uganda's districts. RESULTS: The overall MM baseline median score was 10.3 out of a maximum of 25 with inter-quartile range (IQR) of 8.7 11.7. Facility domain scores (out of a maximum of 5) were as follows: storage management, median score of 2.9 (IQR 2.3-3.4); stock management 2.3 (IQR 2.0 2.8), ordering and reporting 2.2 (IQR 1.3-2.5), and dispensing quality 2.1 (IQR 1.7-2.7). Performance in prescribing quality was 0.9 (IQR 0.4-1.4). Significant regional differences were found: overall scores were highest in the Northern region (10.7; IQR 9.2-12.4) and lowest in the Eastern region (9.6; (IQR 7.8-11.2) (p < 0.001). Overall scores did not differ by facility ownership; however, government facilities scored lower in dispensing and storage and higher in ordering and reporting. Hospitals scored higher overall and in domains other than prescribing and stock management. Districts classified a priori as having high capacity for implementing SPARS had higher scores at baseline compared to lower capacity districts. CONCLUSION: Assessing and building national capacity in MM is needed in both private not-for-profit and government facilities at all levels of care. The indicator-based, multipronged SPARS assessment has been described here, while the strategy's impact has yet to be documented. PMID- 27252870 TI - A study of attitudes, beliefs and organisational barriers related to safe emergency oxygen therapy for patients with COPD (chronic obstructive pulmonary disease) in clinical practice and research. AB - BACKGROUND: Patients can be harmed by receiving too little or too much oxygen. There is ongoing disagreement about the use of oxygen in medical emergencies. METHODS: This was a mixed methods study (survey, telephone interviews and focus groups) involving patients, the public and healthcare professionals (HCPs). RESULTS: 62 patients with chronic obstructive pulmonary disease (COPD), 65 members of the public, 68 ambulance crew members, 22 doctors, 22 nurses and 10 hospital managers took part. For five factual questions about oxygen therapy, the average score for correct answers was 28% for patients with COPD, 33% for the general public and 75% for HCPs. The HCPs had an average score of 66% for five technical questions. Patients (79%) and members of the public (68%) were more likely than HCPs (36%) to believe that oxygen was beneficial in most medical emergencies and less likely to have concerns that it might harm some people (35%, 25% and 68%). All groups had complex attitudes about research into oxygen use in medical emergencies. Many participants would not wish for themselves or their loved ones to have their oxygen therapy determined by a randomised protocol, especially if informed consent was not possible in an emergency situation. CONCLUSIONS: We have found low levels of factual knowledge about oxygen use among patients with COPD and the general public and many false beliefs about the potential benefits and harms of using oxygen. HCPs had a higher level of factual knowledge. All groups had complex attitudes towards research into emergency oxygen use. PMID- 27252871 TI - Direct costs in impaired glucose regulation: results from the population-based Heinz Nixdorf Recall study. AB - OBJECTIVE: For the first time, this population-based study sought to analyze healthcare utilization and associated costs in people with normal fasting glycemia (NFG), impaired fasting glycemia (IFG), as well as previously undetected diabetes and previously diagnosed diabetes linking data from the prospective German Heinz Nixdorf Recall (HNR) study with individual claims data from German statutory health insurances. RESEARCH DESIGN AND METHODS: A total of 1709 participants of the HNR 5-year follow-up (mean age (SD) 64.9 (7.5) years, 44.5% men) were included in the study. Age-standardized and sex-standardized healthcare utilization and associated costs (reported as ? for the year 2008, perspective of the statutory health insurance) were stratified by diabetes stage defined by the participants' self-report and fasting plasma glucose values. Cost ratios (CRs) were estimated using two-part regression models, adjusting for age, sex, sociodemographic variables and comorbidity. RESULTS: The mean total direct healthcare costs for previously diagnosed diabetes, previously undetected diabetes, IFG, and NFG were ?2761 (95% CI 2378 to 3268), ?2210 (1483 to 4279), ?2035 (1732 to 2486) and ?1810 (1634 to 2035), respectively. Corresponding age adjusted and sex-adjusted CRs were 1.53 (1.30 to 1.80), 1.16 (0.91 to 1.47), and 1.09 (0.95 to 1.25) (reference: NFG). Inpatient, outpatient and medication costs varied in order between people with IFG and those with previously undetected diabetes. CONCLUSIONS: The study provides claims-based detailed cost data in well defined glucose metabolism subgroups. CRs of individuals with IFG and previously undetected diabetes were surprisingly low. Data are important for the model-based evaluation of screening programs and interventions that are aimed either to prevent diabetes onset or to improve diabetes therapy as well. PMID- 27252872 TI - Higher fasting plasma glucose is associated with striatal and hippocampal shape differences: the 2sweet project. AB - OBJECTIVE: Previous studies have demonstrated associations between higher normal fasting plasma glucose levels (NFG) (<6.1 mmol/L), type 2 diabetes (T2D) and hippocampal atrophy and other cerebral abnormalities. Little is known about the association between plasma glucose and the striatum despite sensorimotor deficits being implicated in T2D. This study aimed to investigate the relationship between plasma glucose levels and striatal and hippocampal morphology using vertex-based shape analysis. DESIGN: A population-based, cross-sectional study. SETTING: Canberra and Queanbeyan, Australia. PARTICIPANTS: 287 cognitively healthy individuals (mean age 63 years, 132 female, 273 Caucasian) with (n=261) or without T2D (n=26), selected from 2551 participants taking part in the Personality & Total Health (PATH) Through Life study by availability of glucose data, MRI scan, and absence of gross brain abnormalities and cognitive impairment. OUTCOME MEASURES: Fasting plasma glucose was measured at first assessment, and MRI images were collected 8 years later. Shape differences indicating outward and inward deformation at the hippocampus and the striatum were examined with FMRIB Software Library-Integrated Registration and Segmentation Toolbox (FSL-FIRST) after controlling for sociodemographic and health variables. RESULTS: Higher plasma glucose was associated with shape differences indicating inward deformation, particularly at the caudate and putamen, among participants with NFG after controlling for age, sex, body mass index (BMI), hypertension, smoking and depressive symptoms. Those with T2D showed shape differences indicating inward deformation at the right hippocampus and bilateral striatum, but outward deformation at the left hippocampus, compared with participants with NFG. CONCLUSIONS: These findings further emphasize the importance of early monitoring and management of plasma glucose levels, even within the normal range, as a risk factor for cerebral atrophy. PMID- 27252873 TI - Diabetes hinders community-acquired pneumonia outcomes in hospitalized patients. AB - OBJECTIVES: This study aimed to estimate the prevalence of diabetes mellitus (DM) in hospitalized patients with community-acquired pneumonia (CAP) and its impact on hospital length of stay and in-hospital mortality. RESEARCH DESIGN AND METHODS: We carried out a retrospective, nationwide register analysis of CAP in adult patients admitted to Portuguese hospitals between 2009 and 2012. Anonymous data from 157 291 adult patients with CAP were extracted from the National Hospital Discharge Database and we performed a DM-conditioned analysis stratified by age, sex and year of hospitalization. RESULTS: The 74 175 CAP episodes that matched the inclusion criteria showed a high burden of DM that tended to increase over time, from 23.7% in 2009 to 28.1% in 2012. Interestingly, patients with CAP had high DM prevalence in the context of the national DM prevalence. Episodes of CAP in patients with DM had on average 0.8 days longer hospital stay as compared to patients without DM (p<0.0001), totaling a surplus of 15 370 days of stay attributable to DM in 19 212 admissions. In-hospital mortality was also significantly higher in patients with CAP who have DM (15.2%) versus those who have DM (13.5%) (p=0.002). CONCLUSIONS: Our analysis revealed that DM prevalence was significantly increased within CAP hospital admissions, reinforcing other studies' findings that suggest that DM is a risk factor for CAP. Since patients with CAP who have DM have longer hospitalization time and higher mortality rates, these results hold informative value for patient guidance and healthcare strategies. PMID- 27252874 TI - Use of an electronic health record to identify prevalent and incident cardiovascular disease in type 2 diabetes according to treatment strategy. AB - BACKGROUND: The increasing use of electronic health records (EHRs) in clinical practice offers the potential to investigate cardiovascular outcomes over time in patients with type 2 diabetes (T2D). OBJECTIVE: To develop a methodology for identifying prevalent and incident cardiovascular disease (CVD) in patients with T2D who are candidates for therapeutic intensification of glucose-lowering therapy. METHODS: Patients with glycated hemoglobin (HbA1c) >=7% (53 mmol/mol) while receiving 1-2 oral diabetes medications (ODMs) were identified from an EHR (2005-2011) and grouped according to intensification with insulin (INS) (n=372), a different class of ODM (n=833), a glucagon-like peptide receptor 1 agonist (GLP 1RA) (n=59), or no additional therapy (NAT) (n=2017). Baseline prevalence of CVD was defined by documented International Classification of Diseases Ninth Edition (ICD-9) codes for coronary artery disease, cerebrovascular disease, or other CVD with first HbA1c >=7% (53 mmol/mol). Incident CVD was defined as a new ICD-9 code different from existing codes over 4 years of follow-up. ICD-9 codes were validated by a chart review in a subset of patients. RESULTS: Sensitivity of ICD 9 codes for CVD ranged from 0.83 to 0.89 and specificity from 0.90 to 0.96. Baseline prevalent (INS vs ODM vs GLP-1RA vs NAT: 65% vs 39% vs 54% vs 59%, p<0.001) and incident CVD (Kaplan-Meier estimates: 58%, 31%, 52%, and 54%, p=0.002) were greater in INS group after controlling for differences in baseline HbA1c (9.2+/-2.0% vs 8.3+/-1.2% vs 8.2+/-1.3% vs 7.7+/-1.1% (77 vs 67 vs 66 vs 61 mmol/mol), p<0.001) and creatinine (1.15+/-0.96 vs 1.10+/-0.36 vs 1.01+/-0.35 vs 1.07+/-0.45 mg/dL, p=0.001). CONCLUSIONS: An EHR can be an effective method for identifying prevalent and incident CVD in patients with T2D. PMID- 27252875 TI - Age-associated and breed-associated variations in haematological and biochemical variables in young labrador retriever and miniature schnauzer dogs. AB - Breed, sex and age effects on haematological and biochemical variables were investigated in 24 labrador retriever and 25 miniature schnauzer dogs during the first year of life. Blood samples were taken regularly between weeks 8 and 52. White blood cell and red blood cell counts, haemoglobin concentration, haematocrit, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, platelet count as well as total protein, albumin, calcium, phosphate, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, total cholesterol, triglycerides, creatine and urea were evaluated. For all haematological and biochemical parameters, there were significant effects of age on test results. Statistically significant effects for breed and the breed*age interaction on test results were observed for most of the parameters with the exception of haemoglobin. Variations in test results illustrate growth related alterations in body tissue and metabolism leading to dynamic and marked changes in haematological and biochemical parameters, which have to be considered for the interpretation of clinical data obtained from dogs in the first year of life. PMID- 27252876 TI - Observed change in peak oxygen consumption after aortic valve replacement and its predictors. AB - OBJECTIVE: To assess the change in peak oxygen consumption (pVO2) and determine its outcome predictors after aortic valve replacement (AVR) for aortic stenosis (AS). METHODS: Patients with AS and preserved left ventricular ejection fraction who were referred for single AVR had cardiopulmonary exercise testing prior to and 9 months post-AVR. Predictors of outcome for pVO2 were determined by multivariate linear and logistic regression analyses. A significant change in pVO2 was defined as a relative change that was more than twice the coefficient of repeatability by test-retest (>10%). RESULTS: The pre-AVR characteristics of the 37 study patients included the following: median age (range) 72 (46-83) years, aortic valve area index (AVAI) 0.41 (SD 0.11) cm(2)/m(2), mean gradient (MG) 49.1 (SD 15.3) mm Hg and New York Heart Association (NYHA)>=II 27 (73%). Pre-AVR and post-AVR mean pVO2 was 18.5 and 18.4 mL/kg/m(2) (87% of the predicted), respectively, but the change from pre-AVR was heterogeneous. The relative change in pVO2 was positively associated with the preoperative MG (beta=0.50, p=0.001) and negatively associated with brain natriuretic peptide > upper level of normal according to age and gender (beta=-0.40, p=0.009). A relative increase in pVO2 exceeding 10% was found in 9 (24%), predicted by lower pre-AVR AVAI (OR 0.18; 95% CI 0.04 to 0.82, p=0.027) and lower peak O2 pulse (OR 0.94; 95% CI 0.88 to 0.99, p=0.045). Decreases in pVO2 exceeding 10% were found in 11 (30%) and predicted by lower MG (OR 0.93; 95% CI 0.86 to 0.99, p=0.033). CONCLUSIONS: Change in pVO2 was heterogeneous. Predictors of favourable and unfavourable outcomes for pVO2 were identified. PMID- 27252877 TI - Switching between thienopyridines in patients with acute myocardial infarction and quality of care. AB - OBJECTIVE: In acute coronary syndromes, switching between thienopyridines is frequent. The aims of the study were to assess the association between switching practices and quality of care. METHODS: Registry study performed in 213 French public university, public non-academic and private hospitals. All consecutive patients admitted for acute myocardial infarction (MI; <48 hours) between 1/10/2010 and 30/11/2010 were eligible. Clinical and biological data were recorded up to 12 months follow-up. RESULTS: Among 4101 patients receiving thienopyridines, a switch was performed in 868 (21.2%): 678 (16.5%) from clopidogrel to prasugrel and 190 (4.6%) from prasugrel to clopidogrel. Predictors of switch were ST segment elevation MI presentation, admission to a cardiology unit, previous percutaneous coronary intervention, younger age, body weight >60 kg, no history of stroke, cardiac arrest, anaemia or renal dysfunction. In patients with a switch, eligibility for prasugrel was >82% and appropriate use of a switch was 86% from clopidogrel to prasugrel and 20% from prasugrel to clopidogrel. Quality indicators scored higher in the group with a switch and also in centres where the switch rate was higher. CONCLUSIONS: As applied in the French Registry on Acute ST-elevation and non ST-elevation Myocardial Infarction (FAST-MI) registry, switching from one P2Y12 inhibitor to another led to a more appropriate prescription and was associated with higher scores on indicators of quality of care. PMID- 27252879 TI - Congenital heart disease and the cost of mortality. PMID- 27252878 TI - Health utility indexes in patients with acute coronary syndromes. AB - BACKGROUND: Acute coronary syndromes (ACS) have been associated with lower health utilities (HUs) compared with the general population. Given the prognostic improvements after ACS with the implementation of coronary angiography (eg, percutaneous coronary intervention (PCI)), contemporary HU values derived from patient-reported outcomes are needed. METHODS: We analysed data of 1882 patients with ACS 1 year after coronary angiography in a Swiss prospective cohort. We used the EuroQol five-dimensional questionnaire (EQ-5D) and visual analogue scale (VAS) to derive HU indexes. We estimated the effects of clinical factors on HU using a linear regression model and compared the observed HU with the average values of individuals of the same sex and age in the general population. RESULTS: Mean EQ-5D HU 1-year after coronary angiography for ACS was 0.82 (+/-0.16) and mean VAS was 0.77 (+/-0.18); 40.9% of participants exhibited the highest utility values. Compared with population controls, the mean EQ-5D HU was similar (expected mean 0.82, p=0.58) in patients with ACS, but the mean VAS was slightly lower (expected mean 0.79, p<0.001). Patients with ACS who are younger than 60 years had lower HU than the general population (<0.001). In patients with ACS, significant differences were found according to the gender, education and employment status, diabetes, obesity, heart failure, recurrent ischaemic or incident bleeding event and participation in cardiac rehabilitation (p<0.01). CONCLUSIONS: At 1 year, patients with ACS with coronary angiography had HU indexes similar to a control population. Subgroup analyses based on patients' characteristics and further disease-specific instruments could provide better sensitivity for detecting smaller variations in health-related quality of life. PMID- 27252880 TI - Conventional hemodialysis is associated with greater bone loss than nocturnal hemodialysis: a retrospective observational study of a convenience cohort. AB - BACKGROUND: Compared with the general population, end-stage renal disease patients are at increased risk for bone loss and fractures. Nocturnal hemodialysis offers superior calcium-phosphate control and improved uremic clearance compared with conventional hemodialysis. Rates of bone loss by type of hemodialysis are unknown. OBJECTIVES: This study aims to determine whether there are differences in bone loss between frequent nocturnal hemodialysis and conventional hemodialysis. DESIGN: This is a retrospective observational study. SETTING: Participants were selected from two teaching hospitals in downtown Toronto. PARTICIPANTS: The study included 88 participants on dialysis for at least 6 months (52 patients on conventional hemodialysis and 36 patients converted from conventional hemodialysis to nocturnal hemodialysis). Patients on peritoneal dialysis and with previous renal transplants were excluded. MEASUREMENTS: We obtained demographic variables and biochemical data by a chart review. We examined changes in bone mineral density at the hip (femoral neck, total hip) and spine (L1 to L4) measured at baseline and about 1 year in the two groups. METHODS: We used Student's t test for evaluation of between-group mean differences in demographic and biochemical parameters. We used linear regression models adjusted for baseline age, weight, dialysis vintage, markers of mineral metabolism (serum phosphate, serum calcium, and parathyroid hormone), and baseline bone mineral density at the femoral neck, total hip, and lumbar spine to determine the annualized percent change by hemodialysis type. RESULTS: Conventional hemodialysis subjects were older than nocturnal hemodialysis subjects (66 +/- 9 vs 43 +/- 10 years; p < 0.0001) with no significant differences in weight, dialysis vintage, serum phosphate, or parathyroid hormone between the two groups at baseline. In a period over 1 year, conventional hemodialysis compared to nocturnal hemodialysis subjects had significantly greater bone mineral density losses at all sites (1.6 % loss at the lumbar spine (95 % confidence interval (CI) 0.2-3.1), 1.3 % loss at the femoral neck (95 % CI 0.1-2.5), and 1.1 % loss at the total hip (95 % CI 0.1-2.6). LIMITATIONS: Some limitations to this study are the lack of medication administration history, short duration (~1 year), and small sample sizes. CONCLUSIONS: This is the first study comparing bone density between hemodialysis modalities. Our study demonstrates that bone loss is less in nocturnal hemodialysis compared to that in conventional hemodialysis which may result in less fractures. Larger observational studies are ultimately needed to confirm preliminary findings from our study. PMID- 27252881 TI - Hepatic macrophages in liver fibrosis: pathogenesis and potential therapeutic targets. AB - Hepatic macrophages account for the largest non-parenchymal cell population in the liver. Recent studies have found that hepatic macrophages have different functions in different stages of experimental liver fibrosis. Some studies found that there are different types of hepatic macrophages in the liver, although others have suggested that hepatic macrophages could switch to different phenotypes in different environments. Many studies demonstrated that while hepatic macrophages promoted fibrosis through the recruitment of proinflammatory immune cells, and the secretion of proinflammatory cytokines and chemokines in the early stages, these also promoted the resolution of hepatic fibrosis through the secretion of matrix metalloproteinases in the late stages. This article will review the current role played by hepatic macrophages in liver fibrosis and the potential therapeutic targets that modulate hepatic macrophages. PMID- 27252882 TI - Multicentre prospective survey of SeHCAT provision and practice in the UK. AB - OBJECTIVE: A clinical diagnosis of bile acid malabsorption (BAM) can be confirmed using SeHCAT (tauroselcholic ((75)selenium) acid), a radiolabelled synthetic bile acid. However, while BAM can be the cause of chronic diarrhoea, it is often overlooked as a potential diagnosis. Therefore, we investigated the use of SeHCAT for diagnosis of BAM in UK hospitals. DESIGN: A multicentre survey was conducted capturing centre and patient-level information detailing patient care-pathways, clinical history, SeHCAT results, treatment with bile acid sequestrants (BAS), and follow-up in clinics. Eligible data from 38 centres and 1036 patients were entered into a validated management system. RESULTS: SeHCAT protocol varied between centres, with no standardised patient positioning, and differing referral systems. Surveyed patients had a mean age of 50 years and predominantly women (65%). The mean SeHCAT retention score for all patients was 19% (95% CI 17.8% to 20.3%). However, this differed with suspected BAM type: type 1: 9% (95% CI 6.3% to 11.4%), type 2: 21% (95% CI 19.2% to 23.0%) and type 3: 22% (95% CI 19.6% to 24.2%). Centre-defined 'abnormal' and 'borderline' results represented over 50% of the survey population. BAS treatment was prescribed to only 73% of patients with abnormal results. CONCLUSIONS: The study identified a lack of consistent cut off/threshold values, with differing centre criteria for defining an 'abnormal' SeHCAT result. BAS prescription was not related in a simple way to the SeHCAT result, nor to the centre-defined result, highlighting a lack of clear patient care-pathways. There is a clear need for a future diagnostic accuracy study and a better understanding of optimal management pathways. PMID- 27252883 TI - Variety and phosphate fertilizer dose effect on nutrient composition, in vitro digestibility and feeding value of cowpea haulm. AB - BACKGROUND: Cowpea (Vigna unguiculata [L.]) is a legume cultivated throughout most tropical countries and is valued as food and feed for human and livestock respectively. The search for an improved cowpea variety has been on-going with the aim of improving traits such as grain yield, drought and pest resistance. But no information exist on the feeding value of these improved varieties. Phosphate (P) fertilizer application is recommended to augment grain yield in grain legumes but data on the effect of P fertilizer on haulm quality is limited. RESULTS: Two separate experiments were conducted to determine the effect of P fertilizer dose on the nutritive value of haulms from different cowpea varieties (V). In experiment 1, effect of three P doses (30, 60 and 90 kg P2O5/ha) on in vitro gas production (IVGP) characteristics, concentrations of digestible organic matter (DOM), crude protein (CP), acid detergent fiber (ADF) and neutral detergent fiber (NDF) of haulms from five cowpea varieties (Zaayura-SARC 4-75, Songotra-IT97K-499 35, Hewale-IT93K-192-4, IT99K 573-1-1 and Asomdwe-IT94K-410-2) were investigated using the 3 (P) x 5 (V) factorial treatment arrangements in a completely randomized design. In experiment 2, the effects of two P doses (30 and 90 kg P2O5/ha) and two varieties (Zaayura-SARC 4-75 and Hewale-IT93K-192-4) on the voluntary feed intake, live weight, haematology and carcass characteristics of Djallonke lambs were also assessed using a 2(P) x 2(V) factorial treatment arrangement. The V x P interaction significantly affected CP, NDF and ADF with CP concentration increasing with increase in P doses in Zaayura-SARC 4-75 and Asomdwe-IT94K-410-2. Whilst an increase (P < 0.05) in NDF was observed in Songotra-IT97K-499-35and Asomdwe-IT94K-410-2 as P doses increased, the other V only increased from P dose 30 to 60 kg/ha and declined at P dose 90 kg/ha. The ADF decreased (P < 0.05) with increase in P dose for all V with the exception of Songotra-IT97K-499-35. There was a significant V effect on DOM with the highest reported in Zaayura-SARC 4-75 (43.44 %). Daily DM intake, carcass length and blood urea nitrogen of the lambs were significantly affected by the V x P interaction. There was a significant V effect on globulin and P effect on live weight at slaughter, dressed weight, chuck, leg, loin, rib and flank and liver and lungs. CONCLUSION: It can be concluded that nutrient concentrations of cowpea haulms were positively influenced by different P dose and varieties with favorable effects on growth, haematology and carcass composition of lambs. Varieties Zaayura-SARC 4-75 and Hewale-IT93K-192-4 at P dose at 90 kg/ha are recommended to enhance growth performance and carcass yield of Djallonke lambs. PMID- 27252884 TI - Investigation of enhanced hemocompatibility and tissue compatibility associated with multi-functional coating based on hyaluronic acid and Type IV collagen. AB - The biocompatibility of cardiovascular devices has always been considered crucial for their clinical efficacy. Therefore, a biofunctional coating composed of Type IV collagen (CoIV) and hyaluronan (HA) was previously fabricated onto the titanium (Ti) substrate for the application of promoting vascular smooth muscle cell contractile phenotype and improving surface endothelialization. However, the anti-inflammation property, blood compatibility and in vivo tissue compatibility of the HA/CoIV coating, as paramount consideration of cardiovascular materials surface coating, have not been investigated. Thus, in this study, the three crucial properties of the HA/CoIV coating were tested. The platelet adhesion/activation test and the dynamic whole blood experiment implied that the HA/CoIV coating had better blood compatibility compared with Ti substrate and pure CoIV coating. The macrophage adhesion/activation and inflammatory cytokine release (tumor necrosis factor-alpha and interleukin-1) results indicated that the HA/CoIV coating could significantly improve the anti-inflammation property of the Ti substrate. The in vivo implantation of SD rats for 3 weeks' results demonstrated that the HA/CoIV coating caused milder tissue response. All these results suggested that the multi-functional HA/CoIV coating possessed good biocompatibility. This research is anticipated to be potentially applied for the surface modification of cardiovascular stents. PMID- 27252885 TI - Degradation characteristics, cell viability and host tissue responses of PDLLA based scaffold with PRGD and beta-TCP nanoparticles incorporation. AB - This study is aimed to evaluate the degradation characteristics, cell viability and host tissue responses of PDLLA/PRGD/beta-TCP (PRT) composite nerve scaffold, which was fabricated by poly(d, l-lactic acid) (PDLLA), RGD peptide(Gly-Arg-Gly Asp-Tyr, GRGDY, abbreviated as RGD) modified poly-{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]}(PRGD) and beta-tricalcium phosphate (beta-TCP). The scaffolds' in vitro degradation behaviors were investigated in detail by analysing changes in weight loss, pH and morphology. Then, the 3-(4,5-dimethyl-2 thiazolyl) -2,5-diphenyl-2 -H-tetrazolium bromide (MTT) assay and cell live/dead assay were carried out to assess their cell viability. Moreover, in vivo degradation patterns and host inflammation responses were monitored by subcutaneous implantation of PRT scaffold in rats. Our data showed that, among the tested scaffolds, the PRT scaffold had the best buffering capacity (pH = 6.1 6.3) and fastest degradation rate (12.4%, 8 weeks) during in vitro study, which was contributed by the incorporation of beta-TCP nanoparticles. After in vitro and in vivo degradation, the high porosity structure of PRT could be observed using scanning electron microscopy. Meanwhile, the PRT scaffold could significantly promote cell survival. In the PRT scaffold implantation region, less inflammatory cells (especially for neutrophil and lymphocyte) could be detected. These results indicated that the PRT composite scaffold had a good biodegradable property; it could improve cells survival and reduced the adverse host tissue inflammation responses. PMID- 27252886 TI - Sirolimus-loaded CaP coating on Co-Cr alloy for drug-eluting stent. AB - To achieve polymer-free and controllable drug-eluting system, there have been many efforts to modify the surface composition and topography of metal stent. Recently, calcium phosphate is commonly applied to metallic implants as a coating material for fast fixation and firm-implant bone attachment on the account of its demonstrated bioactive and osteoconductive properties. In the present study, the release of sirolimus could be controllable because of immobilization of sirolimus during the process of biomimetic CaP coating forming. A completely new concept is the drug carrier of biomimetic CaP coating with sirolimus for an absorbable drug eluting system, which in turn can serve as a drug reservoir. We here describe the characteristic, mechanisms and drug release in vitro of new drug-eluting system in comparison to conventional system equivalent. Nano-structured calcium phosphate (CaP) coating was formed on the cobalt-chromium (Co-Cr) alloy substrate. By immersing coated sample in solution with sirolimus (rapamycin), the sirolimus could be immobilized in the newly formed CaP layer. The morphology, composition and formation process of the coating were studied with scanning electron microscopy, energy dispersive spectrometer, X-ray diffraction and X-ray photoelectron spectroscopy. The results showed that a uniform CaP coating incorporated with sirolimus was observed on Co-Cr alloy. PMID- 27252887 TI - Biomedical titanium alloys with Young's moduli close to that of cortical bone. AB - Biomedical titanium alloys with Young's moduli close to that of cortical bone, i.e., low Young's modulus titanium alloys, are receiving extensive attentions because of their potential in preventing stress shielding, which usually leads to bone resorption and poor bone remodeling, when implants made of their alloys are used. They are generally beta-type titanium alloys composed of non-toxic and allergy-free elements such as Ti-29Nb-13Ta-4.6Zr referred to as TNTZ, which is highly expected to be used as a biomaterial for implants replacing failed hard tissue. Furthermore, to satisfy the demands from both patients and surgeons, i.e., a low Young's modulus of the whole implant and a high Young's modulus of the deformed part of implant, titanium alloys with changeable Young's modulus, which are also beta-type titanium alloys, for instance Ti-12Cr, have been developed. In this review article, by focusing on TNTZ and Ti-12Cr, the biological and mechanical properties of the titanium alloys with low Young's modulus and changeable Young's modulus are described. In addition, the titanium alloys with shape memory and superelastic properties were briefly addressed. Surface modifications for tailoring the biological and anti-wear/corrosion performances of the alloys have also been briefly introduced. PMID- 27252889 TI - Scientific collaboration: a social network analysis based on literature of animal derived regenerative implantable medical devices. AB - The collaboration network of English publications on animal-derived regenerative implantable medical devices based on tissue engineering technology and its evolving processes and current states were mapped in this paper. A total of 10 159 English papers published before 1 January 2015 were obtained in eight databases. Social network analysis was conducted on these papers by utilizing UCINET software and Statistical Analysis Software for Informatics researched and developed by Peking University. The collaboration network has evolved from scattered formation to single-core dominated, and then to a core-edge one; collaboration has become more frequent and wider; network density and centrality have decreased; USA, UK and China are the top three countries with Wake Forest University, Harvard University and Tufts University being the top three contributing institutions cooperated mostly during the period between 2010 and 2014; plenty of edge institutes exist. In conclusion, more collaboration among different institutions and countries is needed; Edge institutions and developing countries should expand their scope of collaboration. PMID- 27252888 TI - Calcium phosphate nanoparticles-based systems for siRNA delivery. AB - Despite the enormous therapeutic potential of siRNA as a treatment strategy, the delivery is still a problem due to unfavorable biodistribution profiles and poor intracellular bioavailability. Calcium phosphate (CaP) co-precipitate has been used for nearly 40 years for in vitro transfection due to its non-toxic nature and simplicity of preparation. The surface charge of CaP will be tuned into positive by surface modification, which is important for siRNA loading and crossing cell membrane without enzymatic degradation. The new siRNA carrier system will also promote the siRNA escape from lysosome to achieve siRNA sustained delivery and high-efficiency silence. In this review, we focus on the current research activity in the development of CaP nanoparticles for siRNA delivery. These nanoparticles are mainly classified into lipid coated, polymer coated and various other types for discussion. PMID- 27252890 TI - Therapeutic implications of autoantibodies in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by the presence of autoantibodies. Their value for diagnostic/prognostic purposes has been well established. In contrast, their role in established disease and their associations with disease activity is less clear. Moreover, as evidence is accumulating that these autoantibodies are causally involved in certain key aspects of the disease, such as the initiation and perpetuation of joint inflammation or join destruction, autoantibodies in RA can no longer be regarded as mere epiphenomena, but are integral elements of the pathophysiology of RA. PMID- 27252891 TI - Leucocyte subset-specific type 1 interferon signatures in SLE and other immune mediated diseases. AB - OBJECTIVES: Type 1 interferons (IFN-1) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-1 on mixed cell populations. We aimed to define modules of IFN-1 associated genes in purified leucocyte populations and use these as a basis for a detailed comparative analysis. METHODS: CD4+ and CD8+ T cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers and gene expression then determined by microarray. Modules of IFN-1-associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed. RESULTS: 1150 of 1288 IFN-1-associated genes were specific to myeloid subsets, compared with 11 genes unique to T cells. IFN-1 genes were more highly expressed in myeloid subsets compared with T cells. A subset of neutrophil samples from healthy volunteers (HV) and conditions not classically associated with IFN-1 signatures displayed increased IFN-1 gene expression, whereas upregulation of IFN 1-associated genes in T cells was restricted to SLE. CONCLUSIONS: Given the broad upregulation of IFN-1 genes in neutrophils including in some HV, investigators reporting IFN-1 signatures on the basis of whole blood samples should be cautious about interpreting this as evidence of bona fide IFN-1-mediated pathology. Instead, specific upregulation of IFN-1-associated genes in T cells may be a useful biomarker and a further mechanism by which elevated IFN-1 contributes to autoimmunity in SLE. PMID- 27252892 TI - Practice what you preach? An exploratory multilevel study on rheumatoid arthritis guideline adherence by rheumatologists. AB - OBJECTIVES: To assess variation in and determinants of rheumatologist guideline adherence in patients with rheumatoid arthritis (RA), in daily practice. METHODS: In this retrospective observational study, guideline adherence in the first year of treatment was assessed for 7 predefined parameters on diagnostics, treatment and follow-up in all adult patients with RA with a first outpatient clinic visit at the study centre, from September 2009 to March 2011. Variation in guideline adherence was assessed on parameter and rheumatologist level. Determinants for guideline adherence were assessed in patients (demographic characteristics, rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibody (aCCP) positivity, erythrocyte sedimentation rate, erosive disease, comorbidity and the number of available disease modifying anti-rheumatic drug (DMARD) treatment options) and rheumatologists (demographic and practice characteristics, guideline knowledge and agreement, outcome expectancy, cognitive bias, thinking style, numeracy and personality). RESULTS: A total of 994 visits in 137 patients with RA were reviewed. Variation in guideline adherence among parameters was present (adherence between 21% and 72%), with referral to the physician assistant as lowest scoring and referral to a specialised nurse as highest scoring parameter. Variation in guideline adherence among rheumatologists was also present (adherence between 22% and 100%). Patient sex, the number of DMARD options, presence of erosions, comorbidity, RF/aCCP positivity, type of patient and the rheumatologists' scientific education status were associated with adherence to 1 or more guideline parameters. CONCLUSIONS: Guideline adherence varied considerably among the guideline parameters and rheumatologists, showing that there is room for improvement. Guideline adherence in our sample was related to several patient and rheumatologist determinants. PMID- 27252893 TI - Malignancy rates in patients with rheumatoid arthritis treated with tocilizumab. AB - OBJECTIVE: To analyse malignancy rates in patients with rheumatoid arthritis (RA) treated with tocilizumab. METHODS: Patients who received tocilizumab or placebo+methotrexate/disease-modifying antirheumatic drugs in the double-blind phases of 5-phase three trials or who received at least 1 dose of tocilizumab in the long-term extension studies were analysed up to the 2 May 2012 cut-off date. Malignancies were monitored throughout the studies, analysed and adjudicated as malignant by medical review. Risk was compared with that in the general population using standardised incidence ratios (SIRs) based on data from the Surveillance Epidemiology and End Results SEER (US general population) and GLOBOCAN (non-US general population) databases. RESULTS: In total, 4009 patients in the tocilizumab all-exposure population were included. Mean treatment duration was 4.0 years (mean 5.1 (range 0.0-6.8); total observation time was 16 120.1 patient-years (PY). The adjudicated malignancy rate (95% CI) was 1.26/100 PY (1.09 to 1.44) and remained constant over time. The SIR (95% CI) for all malignancies combined, excluding non-melanoma skin cancer, was 1.36 (1.01 to 1.80) for US and 1.81 (1.44 to 2.23) for non-US populations, driven primarily by higher rates in lung and bronchus (US/non-US) malignancies and prostate cancer and non-Hodgkin lymphoma (non-US), in contrast to those for the general populations; these higher rates are in line with those expected in patients with RA or in the geographic regions studied. CONCLUSIONS: Malignancy rates remained stable with long-term tocilizumab treatment, and malignancy types and rates were consistent with those expected in patients with RA. PMID- 27252894 TI - Translation of clinical problems in osteoarthritis into pathophysiological research goals. AB - Osteoarthritis (OA) accounts for more disability among the elderly than any other disease and is associated with an increased mortality rate. The prevalence in Europe will rise in the future since this continent has a strongly ageing population and an obesity epidemic; obesity and age both being major risk factors for OA. No adequate therapeutic options, besides joint replacement, are available, although they are greatly needed and should be acquired by adequate research investments. However, the perspective on OA from a researcher's point of view is not always aligned with the perspective of a patient with OA. Researchers base their views on OA mainly on abnormalities in structure and function while patients consider OA as a collection of symptoms. In this viewpoint paper, we discuss the possibility of translating the most important clinical problems into pathophysiological research goals to facilitate the translation from bench to bedside and vice versa. This viewpoint is the outcome of a dialogue within the 'European League Against Rheumatism study group on OA' and People with Arthritis/Rheumatism across Europe (PARE) representatives. PMID- 27252895 TI - Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set. AB - OBJECTIVE: To evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares was assessed using the agreement coefficient. Construct validity of flare questions was examined: convergent (Spearman's r); discriminant (mean differences between flaring/non-flaring patients); and consequential (proportions with prior treatment reductions and intended therapeutic change postflare). RESULTS: The 849 patients were 75% female, 81% white, 42% were in remission/low disease activity (R/LDA), and 16-32% were flaring at the second visit. Agreement of flare status was low-strong (kappa's 0.17-0.88) and inversely related to RA disease activity level. Flare domains correlated highly (r's>=0.70) with each other, patient global (r's>=0.66) and corresponding measures (r's 0.49-0.92); and moderately highly with MD and patient-reported joint counts (r's 0.29-0.62). When MD/patients agreed the patient was flaring, mean flare domain between-group differences were 2.1-3.0; 36% had treatment reductions prior to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with/without flare and have strong evidence of construct and consequential validity. Ongoing work will identify optimal scoring and cut points to identify RA flares. PMID- 27252896 TI - Bakers' cyst and tibiofemoral abnormalities are more distinctive MRI features of symptomatic osteoarthritis than patellofemoral abnormalities. AB - OBJECTIVE: To investigate which structural MR abnormalities discriminate symptomatic knee osteoarthritis (OA), taking co-occurrence of abnormalities in all compartments into account. METHODS: The Netherlands Epidemiology of Obesity (NEO) study is a population-based cohort aged 45-65 years. In 1285 participants (median age 56 years, 55% women, median body mass index (BMI) 30 kg/m(2)), MRI of the right knee were obtained. Structural abnormalities (osteophytes, cartilage loss, bone marrow lesions (BMLs), subchondral cysts, meniscal abnormalities, effusion, Baker's cyst) at 9 patellofemoral and tibiofemoral locations were scored following the knee OA scoring system. Symptomatic OA in the imaged knee was defined following the American College of Rheumatology criteria. Logistic ridge regression analyses were used to investigate which structural abnormalities discriminate best between individuals with and without symptomatic OA, crude and adjusted for age, sex and BMI. RESULTS: Symptomatic knee OA was present in 177 individuals. Structural MR abnormalities were highly frequent both in individuals with OA and in those without. Baker's cysts showed the highest adjusted regression coefficient (0.293) for presence of symptomatic OA, followed by osteophytes and BMLs in the medial tibiofemoral compartment (0.185-0.279), osteophytes in the medial trochlear facet (0.262) and effusion (0.197). CONCLUSIONS: Baker's cysts discriminate best between individuals with and without symptomatic knee OA. Structural MR abnormalities, especially in the medial side of the tibiofemoral joint and effusion, add further in discriminating symptomatic OA. Baker's cysts may present as a target for treatment. PMID- 27252897 TI - ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters. AB - The objective of this paper is to: describe the phenotype compound heterozygote for mutations in CECR1 in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa. Subsequently, two cerebral lacunar lesions were identified following a brain stroke. Clinical features improved on anti-tumour necrosis factor therapy. The first patient's sister demonstrated early-onset, long-lasting anaemia with mild biological inflammation; at the ages of 3 and 5 years, she had presented 2 acute, transient neurological events with lacunar lesions on MRI. CECR1 sequencing identified both sisters to be compound heterozygous for a p.Tyr453Cys mutation and a previously undescribed deletion of exon 7. ADA2 activity was reduced by 50%. Neutrophil-stimulated genes were not overexpressed, but interferon-stimulated genes were. The expression of a panel of other cytokine transcripts was not significantly altered. In conclusion, searching for CECR1 mutation or assessing ADA2 activity should be considered in patients with an atypical presentation of inflammatory disease. PMID- 27252898 TI - Performance of matrices developed to identify patients with early rheumatoid arthritis with rapid radiographic progression despite methotrexate therapy: an external validation study based on the ESPOIR cohort data. AB - INTRODUCTION: Use of prediction matrices of risk or rapid radiographic progression (RRP) for early rheumatoid arthritis (RA) in clinical practice could help to better rationalise the first line of treatment. Before use, they must be validated in populations that have not participated in their construction. The main objective is to use the ESPOIR cohort to validate the performance of 3 matrices (ASPIRE, BEST and SONORA) to predict patients at high risk of RRP at 1 year of disease despite initial treatment with methotrexate (MTX). METHODS: We selected from the ESPOIR cohort 370 patients receiving MTX or leflunomide (LEF) for >=3 months within the first year of follow-up. Patients were assessed clinically every 6 months, and structural damage progression seen on radiography was measured by the van der Heijde-modified Sharp score (vSHS) at 1 year. RRP was defined as an increase in the vSHS>=5 points during the first year. RESULTS: At 1 year, the mean vSHS score was 1.7+/-5.0 and 46 patients had RRP. The ASPIRE matrix had only moderate validity in the ESPOIR population, with area under the receiver operating characteristic curve (AUC) <0.7. The AUC for the BEST and SONORA matrices were 0.73 and 0.76. Presence of rheumatoid factor (RF)-or anti citrullinated protein antibodies (ACPAs) and initial structural damage were always predictive of RRP at 1 year. Disease Activity Score in 28 joints (DAS28) and C reactive protein (ASPIRE threshold) were not associated with RRP. CONCLUSIONS: Matrices to identify patients at risk of RRP tested in the ESPOIR cohort seem to perform moderately. There is no matrix that shows clearly superior performance. PMID- 27252899 TI - Applications of species accumulation curves in large-scale biological data analysis. AB - The species accumulation curve, or collector's curve, of a population gives the expected number of observed species or distinct classes as a function of sampling effort. Species accumulation curves allow researchers to assess and compare diversity across populations or to evaluate the benefits of additional sampling. Traditional applications have focused on ecological populations but emerging large-scale applications, for example in DNA sequencing, are orders of magnitude larger and present new challenges. We developed a method to estimate accumulation curves for predicting the complexity of DNA sequencing libraries. This method uses rational function approximations to a classical non-parametric empirical Bayes estimator due to Good and Toulmin [Biometrika, 1956, 43, 45-63]. Here we demonstrate how the same approach can be highly effective in other large-scale applications involving biological data sets. These include estimating microbial species richness, immune repertoire size, and k-mer diversity for genome assembly applications. We show how the method can be modified to address populations containing an effectively infinite number of species where saturation cannot practically be attained. We also introduce a flexible suite of tools implemented as an R package that make these methods broadly accessible. PMID- 27252901 TI - The Relationship Between Patients' Anthropometric Characteristics and Depth of Spinal Needle Insertion. AB - BACKGROUND: Many surgeries are performed under spinal anesthesia. Inexperienced practitioners may find it difficult to obtain subarachnoid access. OBJECTIVES: This study aimed to examine the relationship between patients' anthropometric characteristics and depth of spinal needle insertion to the subarachnoid cavity. PATIENTS AND METHODS: 385 patients with ASA class I - II, aged 18 - 65 years and undergoing elective surgery of the lower abdomen and extremities under spinal anesthesia, were selected for this cross-sectional study. The patients' demographic characteristics, body mass index (BMI), and anthropometric characteristics (height, weight, waist circumference, and arm circumference) were recorded. Linear regression and t-student tests were used to study the relationship between anthropometric characteristics and BMI, and depth of needle insertion. RESULTS: Of the 385 patients studied, 88 were female and 297 were male. There was a strong correlation between the depth of needle insertion and BMI (24.9 +/- 3.9), and between depth and weight/height ratio (r = 0.95 and r = 0.92, respectively). There was no significant correlation between depth of needle insertion and weight, height, gender, or arm circumference, when considered separately. The statistical predicting models showed that the following relationship was observed between the needle depth and the weight/height ratio: A: needle depth = 0.69 + (10.1 * weight/height); B: needle depth = 0.56 + (0.18 * BMI). CONCLUSIONS: The results of this study show that there is a strong relationship between depth of needle insertion and BMI, and between depth and the weight/height ratio; appropriate depths can be determined according to the equations obtained. PMID- 27252900 TI - Notochord Cells in Intervertebral Disc Development and Degeneration. AB - The intervertebral disc is a complex structure responsible for flexibility, multi axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID- 27252903 TI - Effective Bolus Dose of Sufentanil to Attenuate Cardiovascular Responses in Laryngoscopic Double-Lumen Endobronchial Intubation. AB - BACKGROUND: Sufentanil is a potent opioid analgesic frequently used in clinical anesthesia. Double-lumen endobronchial intubation induces profound cardiovascular responses in comparison with ordinary endotracheal intubation because of the larger tube diameter and direct irritation of the carina. OBJECTIVES: The purpose of this study was to determine the effective bolus dose of sufentanil to attenuate hemodynamic changes in response to laryngoscopic double-lumen endobronchial intubation. PATIENTS AND METHODS: We randomly assigned 72 patients aged 18 - 65 years and with an American Society of Anesthesiologists physical status of 1 or 2 to one of four sufentanil dose groups: NS, S0.1, S0.2, or S0.3. The respective doses for the groups were as follows: normal saline, 0.1 mcg/kg of sufentanil, 0.2 mcg/kg of sufentanil, and 0.3 mcg/kg of sufentanil. Blood pressure and heart rate were recorded during the pre-anesthesia period at baseline, pre-intubation, immediate post-intubation, and every minute during 5 minutes after intubation. RESULTS: Baseline mean arterial pressures in the NS, S0.1, S0.2, and S0.3 groups were 89.8 +/- 12.1, 89.2 +/- 10.9, 88.8 +/- 13.6, and 90.7 +/- 11.1, respectively. At immediate post-intubation, the mean arterial pressures in the NS, S0.1, S0.2, and S0.3 groups were 129.7 +/- 14.7, 120.7 +/- 14.2, 120.8 +/- 17.2, and 96.7 +/- 10.4, respectively. At immediate post intubation, the mean arterial pressure in the NS, S0.1, and S0.2 groups significantly increased from baseline (P < 0.001), but the S0.3 group showed no difference. In the time point comparison at immediate post- intubation, the S0.3 group had a significantly lower mean arterial pressure than did the NS, S0.1, and S0.2 groups (P < 0.001). CONCLUSIONS: We found that 0.3 mcg/kg of sufentanil attenuates cardiovascular responses to double-lumen endobronchial intubation without adverse effects. PMID- 27252902 TI - Novel Treatment of Radicular Pain With a Multi-Mechanistic Combination Topical Agent: A Case Series and Literature Review. AB - INTRODUCTION: Pharmacologic treatment of radicular pain with oral medications is limited by adverse effects and concern for dependence. While topical formulations have been explored in pain research, there is no published literature evaluating the efficacy in radicular pain. We present the first three cases of radicular pain successfully treated with a topical formulation of diclofenac, ibuprofen, baclofen, cyclobenzaprine, bupivacaine, gabapentin, and pentoxifylline (T7). CASE PRESENTATION: Case series evaluating T7 for treatment of radicular pain in a single, outpatient pain center. Pain was rated on the numeric rating scale (NRS) on initial evaluation and follow up after a trial of T7. One to two grams of T7 was applied to the affected area 3 - 4 times daily in addition to the patient's baseline pharmacologic management. Three patients with median age of 50 (range, 39 to 65) and diagnosis of cervical and/or lumbosacral radicular pain participated. Two of the three had chronic radicular pain despite use of analgesic agents, spinal injections and failed spinal surgery syndrome. Each reported subjective improvement in radicular pain, function and sleep. There was an average decrease in NRS score consistent with 30% - 40% global improvement in symptoms, clinically significant based on the minimal clinically important difference for radicular pain. T7 was well tolerated without adverse reactions. Surgery was prevented or delayed in all cases. CONCLUSIONS: This is the first report of the successful treatment of radicular pain with a topical agent. This highlights the need for randomized, prospective study of both single and compounded topical agents for treatment of radicular pain. PMID- 27252904 TI - Comparison of the Effects of Subcutaneous Versus Continuous Infusion of Heparin on Key Inflammatory Parameters Following Sepsis. AB - BACKGROUND: Sepsis is the result of the interaction between inflammatory mediators and coagulation pathway. Unfractionated heparin may play a role as an anti-inflammatory agent beyond its anticoagulatory effect in sepsis. As a result, it may cause reduction in organ failure rate in patients with sepsis due to its impact on both inflammatory and coagulation process. OBJECTIVES: The aim of this study was to evaluate the anti-inflammatory effects of heparin in sepsis. Plasma plasminogen activator inhibitor-1 (PAI-1) as an inflammatory mediator and urinary necoutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney injury were investigated. PATIENTS AND METHODS: This prospective, randomized controlled trial was conducted in a 32-bed intensive care unit. Thirty patients with sepsis were randomized to receive heparin infusion of 500 units/hour or 5000 units of heparin three times a day, subcutaneously. The plasma level of PAI-1 and urinary level of NGAL were determined at day 0, 2 and 7. RESULTS: The infusion group had a lower plasma PAI-1 level compared to the subcutaneous group at day 7 (11.3 +/- 1.6 vs. 16.5 +/- 4.2; P = 0.003). The urinary NGAL level was lower in the infusion group at day 2 (131.3 +/- 11.9 vs. 151.2 +/- 20.6; P = 0.014); however, at day 7 the NGAL level was decreased in the subcutaneous group as much as the infusion group and there was no significant difference between the two groups. There was no significant difference in the acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores between the two groups at day 0, 2 and 7. CONCLUSIONS: Low-dose heparin infusion compared to subcutaneous heparin can decrease the plasma PAI-1 and urinary NGAL levels more rapidly. It can be related to anti-inflammatory effects of heparin, which may be more prominent in infusion route. PMID- 27252905 TI - Predictors of Difficult Intubation Among Malay Patients in Indonesia. AB - BACKGROUND: Failure to maintain an adequate airway can lead to brain damage and death. To reduce the risk of difficulty in maintaining an airway during general anesthesia, there are several known predictors of difficult intubation. People with a Malay background have different craniofacial structures in comparison with other individuals. Therefore, different predictors should be used for patients of Malay race. OBJECTIVES: The aim of this study was to determine the ability to predict difficult visualization of the larynx (DVL) in Malay patients based on several predictors, such as the modified Mallampati test (MMT), thyromental distance (TMD), and hyomental distance ratio (HMDR). PATIENTS AND METHODS: This cross-sectional study included 277 consecutive patients requiring general anesthesia. All subjects were evaluated using the MMT, TMD, and HMDR, and the cut off points for the airway predictors were Mallampati III and IV, < 6.5 cm, and < 1.2, respectively. During direct laryngoscopy, the laryngeal view was graded using the Cormack-Lehane (CL) classification. CL grades III and IV were considered difficult visualization. The area under the curve (AUC), sensitivity, and specificity for each predictor were calculated both as sole and combined predictors. Logistic regression analysis was used to determine independent predictors of DVL. RESULTS: Difficulty in visualizing the larynx was found in 28 (10.1%) patients. The AUC, sensitivity, and specificity for the three airway predictors were as follows: MMT: 0.614, 10.7%, and 99.2%; HMDR: 0.743, 64.2%, and 74%; and TMD: 0.827, 82.1%, and 64.7%. The combination providing the best prediction in our study involved the MMT, HMDR, and TMD with an AUC, sensitivity, and specificity of 0.835, 60.7%, and 88.8%, respectively. Logistic regression analysis showed that the MMT, HMDR, and TMD were independent predictors of DVL. CONCLUSIONS: The TMD, with a cut-off point of 65 mm, had superior diagnostic value compared with the HMDR and Mallampati score. Therefore, the TMD could be used in Malay patients to predict the difficulty of larynx visualization during laryngoscopy. PMID- 27252906 TI - The Lateral Position Improved Airway Patency in Anesthetized Patient With Burn Induced Cervico-Mento-Sternal Scar Contracture. AB - A 78-year-old woman with burn-induced cervico-mento-sternal scar contracture was scheduled for laparoscopic cholecystectomy. During inhalational induction of sevoflurane, her airway patency deteriorated. The right lateral position and assist ventilation using a breathing bag dramatically improved her airway patency. PMID- 27252907 TI - Is the Pressure Control Mode for Pediatric Anesthesia Machines Really Required? PMID- 27252908 TI - Evaluating Persistent Postoperative Pain in One Tertiary Hospital: Incidence, Quality of Life, Associated Factors, and Treatment. AB - BACKGROUND: Persistent postoperative pain (PPP) is defined as persistent pain after surgery of greater than three months' duration. OBJECTIVES: Identify the incidence of PPP in our hospital and its associated factors; evaluate quality of life (QoL) and treatment of patients. PATIENTS AND METHODS: We conducted an observational prospective study in adults proposed to various types of surgery using the brief pain inventory short form preoperatively (T0), one day after surgery, and three months later (T3). If the patient had pain at T3 and other causes of pain were excluded, they were considered to have PPP, and the McGill Pain Questionnaire Short Form was applied. QoL was measured with the EuroQol 5 dimension questionnaire (EQ-5D). RESULTS: One hundred seventy-five patients completed the study. The incidence of PPP was 28%, and the affected patients presented lower QoL. The majority referred to a moderate to severe level of interference in their general activity. Cholecystectomies were less associated with PPP, and total knee/hip replacements were more associated with it. Preoperative pain, preoperative benzodiazepines or antidepressants, and more severe acute postoperative pain were associated with the development of PPP. Half of the patients with PPP were under treatment, and they refer a mean symptomatic relief of 69%. CONCLUSIONS: This study, apart from attempting to better characterize the problem of PPP, emphasizes the lack of its treatment. PMID- 27252910 TI - Prevalence of Urogenital Mycoplasmas in Iran and Their Effects on Fertility Potential: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Urogenital mycoplasmas are potentially pathogenic species causing genitourinary tract infections that may be initially asymptomatic but can progress and lead to severe complications and threaten reproductive health. However, the overall prevalence rate of this bacterium and its probable impacts on fertility potential have yet to be determined. METHODS: We searched both English and Persian electronic databases using key words such as "Mycoplasma," "Ureaplasma," "M. hominis," "M. genitalium," "U. urealyticum," "U. parvum," "prevalence," and "Iran". Finally, after some exclusion, 29 studies from different regions of Iran were included in our study, and a meta-analysis was performed on collected data. RESULTS: Urogenital mycoplasmas prevalence for women and men was high and ranged from 2%-40.5% and 2%-44.3%, respectively. The pooled prevalence in the male population was 11.1% (95% CI, 7.4%-16.4%) and in female was 12.8% (95% CI, 9.8%-16.5%). The prevalence of these bacteria was significantly higher in infertile men compared with that in fertile men. A high level of heterogeneity was observed for both men (I(2) = 92.4%; P<0.001) and women (I(2) = 93.3%; P<0.001). Some evidence for publication bias was observed in both men [Egger's test (two-tailed P=0.0007), and Begg's test (two-tailed P=0.0151)] and women [Egger's test (two-tailed P=0.0006), and Begg's test (two tailed P=0.0086)] analysis. CONCLUSION: Since urogenital mycoplasmas may play a role in male infertility, screening strategies, particularly for asymptomatic individuals, and treatment of infected ones, which can reduce consequent complications, looks to be necessary. PMID- 27252909 TI - Cap-Independent Translational Control of Carcinogenesis. AB - Translational regulation has been shown to play an important role in cancer and tumor progression. Despite this fact, the role of translational control in cancer is an understudied and under appreciated field, most likely due to the technological hurdles and paucity of methods available to establish that changes in protein levels are due to translational regulation. Tumors are subjected to many adverse stress conditions such as hypoxia or starvation. Under stress conditions, translation is globally downregulated through several different pathways in order to conserve energy and nutrients. Many of the proteins that are synthesized during stress in order to cope with the stress use a non-canonical or cap-independent mechanism of initiation. Tumor cells have utilized these alternative mechanisms of translation initiation to promote survival during tumor progression. This review will specifically discuss the role of cap-independent translation initiation, which relies on an internal ribosome entry site (IRES) to recruit the ribosomal subunits internally to the messenger RNA. We will provide an overview of the role of IRES-mediated translation in cancer by discussing the types of genes that use IRESs and the conditions under which these mechanisms of initiation are used. We will specifically focus on three well-studied examples: Apaf-1, p53, and c-Jun, where IRES-mediated translation has been demonstrated to play an important role in tumorigenesis or tumor progression. PMID- 27252911 TI - Economic Evaluation of Health Services Costs During Pandemic Influenza A (H1N1) Pdm09 Infection in Pregnant and Non-Pregnant Women in Spain. AB - BACKGROUND: The healthcare and socio-economic burden resulting from influenza A (H1N1) pdm09 in Spain was considerable. Our aim was to estimate and compare the management (resource utilization) and economic healthcare impact in an at-risk group of unvaccinated pregnant women with an unvaccinated group of non-pregnant woman of childbearing age (15-44 yr old). METHODS: We addressed this question with a longitudinal, observational, multicentre study. Inputs were the requirements in managing both groups of women. Outcome measures were healthcare costs. Direct healthcare (including medical utilisation, prescriptions of antivirals, medication, diagnostic tests, and hospitalisation) costs and indirect (productivity loss) costs were considered. Unit of cost was attributed to the frequency of health service resources utilisation. The mean cost per patient was calculated in this group of women. RESULTS: We found that the influenza clinical pattern was worse in non-pregnant women as they had a high medical risk of 20.4% versus 6.1% of pregnant women. Non-pregnant required more antipyretics and antibiotics, and needed more health service resource utilisation (338 medical visits in non-pregnant women vs. 42 in pregnant women). The total cost of non pregnant women was higher (?4,689.4/non-pregnant and ?2,945.07/pregnant). CONCLUSIONS: Cost per (H1N1) pdm09 was lower for pregnant women, probably due to more preventive measures adopted for their protection in Spain. The highest costs were incurred by hospitalisations/day and work absenteeism for non-pregnant than for pregnant women. These data will allow better future pandemic influenza planning. PMID- 27252912 TI - Predictive Role of Serum Tumor Markers in Diagnosis of Pulmonary Tuberculosis. AB - BACKGROUND: The diagnosis of pulmonary tuberculosis (PTB) is complicated and time consuming currently. There was association of PTB with serum tumor markers. In this study we aimed to evaluate the predictive role of serum CA125, CA199 and CEA as diagnostic tools for PTB. METHODS: This study was designed as a case-control study with 565 subjects who visited the Yijishan Hospital from Jun to Dec in 2014.This case-control study matched as for age and sex with 113 cases and 452 controls. Serum CA125, CA199 and CEA levels were detected by electrochemiluminescence instrument. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value on PTB. RESULTS: Serum levels of CA125, CA199 and CEA in PTB patients were significantly higher than those in control group (P<0.001). There was no significantly different of three tumor markers between initial treatment group and retreatment group. The logistic regression analysis showed that CA125 was an impact factor to PTB. The ROC analysis revealed that AUC of CA125 was 0.966 (95%CI: 0.951-0.981), the sensitivity, specificity in serum and cut-off were 95.6%, 85.0% and 10.30 U/ml, respectively. CONCLUSION: The serum CA125 has potential good diagnostic performance for PTB. PMID- 27252913 TI - Risk Factors for Primary Pulmonary TB in Almaty Region, Kazakhstan: A Matched Case-Control Study. AB - BACKGROUND: This study examined the association between incident pulmonary tuberculosis (TB) and social and behavioral characteristics in Almaty Oblast, Kazakhstan from 2012 to 2013. METHODS: We used a matched case-control design to estimate the role of factors for acquiring pulmonary TB. Totally 324 individuals were recruited from Sep 2012 to Mar 2013. Participants included 110 TB index cases with newly detected pulmonary TB. Each case was matched with one household and one community control. A total of 107 household and 107 community controls were included to the study. Adjusted odds ratios measuring associations between TB and risk factors were calculated by using a conditional multiple logistic regression analysis. RESULTS: TB cases were more likely to be younger, recent smokers and have diabetes, when compared to household controls. Between TB cases and community controls, TB was significantly associated with age, non-married family status, living in a rented home, recent smoker, and having diabetes. Comparing TB cases with community controls, we found that foreign birth was marginally associated with incident TB case status. CONCLUSION: Our findings confirm the role of modifiable risk factors for TB in Kazakhstan; highlighting the importance of developing interventions addressing social determinants and proximate risk factors for high TB burden regions. PMID- 27252914 TI - Construct Validity of Symptom Checklist-90-Revised (SCL-90-R) and General Health Questionnaire-28 (GHQ-28) in Patients with Drug Addiction and Diabetes, and Normal Population. AB - BACKGROUND: Given that validity is the baseline of psychological assessments, there is a need to provide evidence-based data for construct validity of such scales to advance the clinicians for evaluating psychiatric morbidity in psychiatric and psychosomatic setting. METHODS: This comparative cross-sectional study aimed to investigate the construct validity of the Malaysian version of the GHQ-28 and the SCL-90-R. The sample comprised 660 individuals including diabetics, drug dependents, and normal population. The research scales were administered to the participants. Convergent and discriminant validity of both scales were investigated by Confirmatory Factor Analysis (CFA) using AMOS. The Pearson correlation coefficient was utilized to obtain the relationship between the two scales. RESULTS: The internal consistency of the GHQ-28 and SCL-90-R were highly acceptable, and confirmatory factor analysis confirmed the convergent validity of both scales. The results of this study revealed that the construct validity of GHQ-28 was acceptable, whereas discriminant validity of SCL-90-R was not adequate. According to Pearson correlation coefficient the relationships between three common subscales of the GHQ-28 and SCL-90-R were significantly positive; somatization (r=0.671, P<0.01), Anxiety (r=0.728, P<0.01), and Depression (r=0.660, P <0.01). CONCLUSIONS: This study replicated the construct of the Malaysian version of GHQ-28, yet failed to support the nine-factor structure of the SCL-90-R. Therefore, multidimensionality of the SCL-90-R as clinical purposes is questionable, and it may be a better unitary measure for assessing and screening mental disorders. Further research need to be carried out to prove this finding. PMID- 27252915 TI - Association of the -243A>G, +61450C>A Polymorphisms of the Glutamate Decarboxylase 2 (GAD2) Gene with Obesity and Insulin Level in North Indian Population. AB - BACKGROUND: Obesity associated with type 2 diabetes, and hypertension increased mortality and morbidity. Glutamate decarboxylase 2 (GAD2) gene is associated with obesity and it regulate food intake and insulin level. We investigated the association of GAD-2gene -243A>G (rs2236418) and +61450C>A (rs992990) polymorphisms with obesity and related phenotypes. METHODS: Insulin, glucose and lipid levels were estimated using standard protocols. All subjects were genotyped (PCR-RFLP) method. RESULTS: The -243A>G polymorphism of the GAD-2 gene was significantly associated with higher risk of obesity (P<0.05). CONCLUSION: GAD-2 gene polymorphisms influence obesity and related phenotype in complex manner, probably by regulating the food intake, insulin and body weight. PMID- 27252916 TI - Application of Predictive Nursing Reduces Psychiatric Complications in ICU Patients after Neurosurgery. AB - BACKGROUND: Our aim was to investigate the effects of clinical application of perioperative predictive nursing on reducing psychiatric complications in Intensive Care Unit (ICU) patients after neurosurgery. METHODS: A total of 129 patients who underwent neurosurgery and received intensive care were enrolled in our study from February 2013 to February 2014. These patients were divided into two groups: the experimental group (n=68) receiving predictive nursing before and after operation, and the control group (n=61) with general nursing. Clinical data including length of ICU stay, duration of the patients' psychiatric symptoms, form and incidence of adverse events, and patient satisfaction ratings were recorded, and their differences between the two groups were analyzed. RESULTS: The duration of psychiatric symptoms and the length of ICU stay for patients in the experimental group were significantly shorter than those in the control group (P<0.05). The incidence of adverse events and psychiatric symptoms, such as sensory and intuition disturbance, thought disturbance, emotional disorder, and consciousness disorder, in the experimental group was significantly lower than that in the control group (P<0.05). Patient satisfaction ratings were significantly higher in the experimental group than those in the control group (P<0.05). CONCLUSION: Application of predictive nursing on ICU patients who undergo neurosurgery could effectively reduce the incidence of psychiatric symptoms as well as other adverse events. Our study provided clinical evidences to encourage predictive nursing in routine settings for patients in critical conditions. PMID- 27252917 TI - Factors Associated with Physical Activity among Macedonian Adolescents in Albanian Ethnic Community. AB - BACKGROUND: The purpose of this study was to determine the relationship of demographic, psychological, social and environmental factors with physical activity and to determine whether indicators of physical activity differ by gender among Macedonian adolescents from Albanian ethnic community from 11 to 14 yr (N = 886). METHODS: Research were conducted in 2014 in several primary schools randomly selected from Tetovo and Gostivar region of the R. Macedonia. Students completed a questionnaire which examined their level of participation in physical activity and sedentary behavior along with a number of potential correlates. Hierarchical regression was used to explore the relationship between hypothesised factors and physical activity. RESULTS: The boys unlike the girls showed significantly higher levels of physical activity (P=0.001). Respondents of both genders who perceive greater benefits from the physical activity (P=0.010). They have more confidence in their abilities (P=0.001), enjoy more in the physical activities (P=0.016), perceive greater social support from friends (P=0.008) and parents (P=0.001) and have higher levels of physical activity. CONCLUSIONS: The results indicate the importance of developing a national plan and program to promote physical activity in order to help young people to change unhealthy lifestyle habits and increase the physical activity, thus improving their health. PMID- 27252918 TI - Characterization of Staphylococcus aureus Biofilm Formation in Urinary Tract Infection. AB - BACKGROUND: The aim of this study was to investigate the antibiotic susceptibility pattern as well as the phenotypic and genotypic biofilm formation ability of Staphylococcus aureus isolates from patients with urinary tract infection (UTI). METHODS: A total of 39 isolates of S. aureus were collected from patients with UTI. The antibiotic susceptibility patterns of the isolates were determined by the Kirby-Bauer disk-diffusion. We used the Modified Congo red agar (MCRA) and Microtiter plate methods to assess the ability of biofilm formation. All isolates were examined for determination of biofilm related genes, icaA, fnbA, clfA and bap using PCR method. RESULTS: Linezolid, quinupristin/dalfopristin and chloramphenicol were the most effective agents against S. aureus isolates. Overall, 69.2% of S. aureus isolates were biofilm producers. Resistance to four antibiotics such as nitrofurantoin (71.4% vs. 28.6%, P=0.001), tetracycline (57.7% vs. 42.3%, P=0.028), erythromycin and ciprofloxacin (56% vs. 44%, P=0.017) was higher among biofilm producers than non biofilm producers. The icaA, fnbA and clfA genes were present in all S. aureus isolates. However, bap gene was not detected in any of the isolates. CONCLUSION: Our findings reinforce the role of biofilm formation in resistance to antimicrobial agents. Trimethoprimsulfamethoxazole and doxycycline may be used as an effective treatment for UTI caused by biofilm producers S. aureus. Our results suggest that biofilm formation is not dependent to just icaA, fnbA, clfA and bap genes harbor in S. aureus strains. PMID- 27252919 TI - Technical Efficiency of Hospitals in Tehran, Iran. AB - BACKGROUND: Nowadays, restriction on access and optimum use of resources is the main challenge of development in all organizations. Therefore, the aim of this study was to determine the technical efficiency and its factors, influencing hospitals of Tehran. METHODS: This research was a descriptive-analytical and retrospective study conducted in 2014-2015. Fifty two hospitals with public, private, and social security ownership type were selected for this study. The required data was collected by a researcher-made check list in 3 sections of background data, inputs and outputs. The data was analyzed by DEAP 1.0.2, and STATA-13 technique. RESULTS: Seventeen (31/48) of hospitals had the efficiency score of 1 as the highest technical efficiency. The highest average score of efficiency was related to social security hospitals as 84.32, and then the public and private hospitals with the average of 84.29 and 79.64 respectively. Tobit regression results showed that the size, type of practice, and ownership of hospitals were effective on the degree of their technical efficiency. However, there was no significant correlation between teaching / non-teaching hospitals with technical efficiency. CONCLUSION: Establishment of competition system among hospitals, constitution of medium size hospitals and allocation of budget to hospitals based on national accreditation system are recommended. PMID- 27252920 TI - Epidemiologic Pattern of Fatal Traffic Injuries among Iranian Drivers; 2004-2010. AB - BACKGROUND: Due to their specific nature, such as high incidence, high intensity and direct involvement of all members of society, traffic injuries are of particular importance. Through a mega data, this study investigated the epidemiological aspects and depict current situation of road traffic injuries in Iran. METHODS: Using legal medicine and traffic police data, deaths from road traffic injuries in men were predicted through determining the most appropriate model for death using time series statistical models; and then most important human factors associated with it in a period of 6 yr in Iran was analyzed using multi-nominal regression model. RESULTS: The frequency of deaths from traffic injuries in the last seven years was 172,834 cases and the number of deaths at the accident scene was 42798 cases, of which 24.24% (41,971 cases) were recorded by the Traffic Police experts. Death rate from traffic injuries has been declined from 38 cases per 100,000 people in 2004 to 31 cases per 100,000 people between 2009 and 2010. Fatigue and sleepiness (AOR=10.36, 95% CI: 8.41-13.3) was the most significant human risk factors for death outcome in the urban and suburban traffic injuries. According to the predictions, the death rate is about 16488 (CI 95%, 8531-24364) for the year 2012. CONCLUSION: Despite all measures to prevent such injuries, even fatal injuries have still a high incidence. Intervention in the human risk factors field would be more effective due to their important roles in traffic injuries in Iran. PMID- 27252921 TI - Observable Effects of Atmospheric Pollution on Outpatient and Inpatient Morbidity in Bulgaria. AB - BACKGROUND: One of Europe's most well-developed industrial regions is found in the Republic of Bulgaria. The industrialization of the region has a big impact on air pollution. Thermal power plant "Maritza East" (the largest of its kind in southeastern Europe), the army training range, machine manufacturers, household heating and high volume of automobile traffic are all major sources of pollution in the region. METHODS: A five year study (2009-2013) followed yearly concentrations of principal atmospheric pollutants such as sulfur dioxide, dust, nitrogen dioxide, lead aerosols and hydrogen sulfide, and the way in which those levels had an effect on morbidity (outpatient and inpatient medical care) in the area. Statistical processing of data has been completed to represent and analyze the collected data in nonparametric and alternative format. RESULTS: Atmospheric pollution affects human health directly through pathological changes in the human organism. The registered outpatient care provided for the period 2009-2013 is highest for diseases of the cardiovascular system (11.85%), the respiratory system (17.34%) and the genitourinary system (9.76%). The registered rate of hospitalization for the same period is for diseases of the digestive system (11.90%), the cardiovascular system (11.85%), respiratory system (10.86%) and the genitourinary system (8.88%). CONCLUSION: The observed period shows a decrease in average yearly concentrations of the principal atmospheric pollutants in the industrial region (Bulgaria) and reflects a decrease in morbidity based on outpatient care and an increase in morbidity by inpatient care (hospitalization). Our findings should be corroborated in future longitudinal studies. PMID- 27252922 TI - The First Serological Study of Coxiella burnetii among Pregnant Women in Iran. AB - BACKGROUND: Q fever is a zoonotic disease caused by Coxiella burnetii. There is no information about this disease in pregnant women in Iran. The aim of this study was to investigate the seroprevalence of C. burnetii infection among pregnant women in southwestern (Ahvaz) and northern (Parsabad) Iran and further to comparison its prevalence in normal and abnormal pregnancies. METHODS: A total of 400 samples were collected randomly from pregnant women who referred to diagnostic laboratories of Ahvaz and Parsabad in 2014. An indirect ELISA kit, designed in Veterinary Faculty, was used to detect the specific antibodies against phase II humanC. burnetii in serum samples. RESULTS: The overall prevalence of C. burnetii in sera from pregnant women was 29.3% (95% confidence interval (CI): 25-34%). The prevalence of C. burnetii infection was significantly different in Ahvaz and Parsabad with, respectively, 22 (95% CI: 16-28%) and 36.5% (95% CI: 30-43%). Total prevalence of C. burnetii infection in serum was significantly higher in women with abnormal pregnancy history (39.8%) compared with normal pregnancies (23.8%). Furthermore, maternal age had significant association with seropositivity and the prevalence increased with maternal age. This could be due to higher probability of encountering C. burnetii in older women. CONCLUSION: The present study demonstrated ahigh seroprevalence of C. burnetii infection among pregnant women in Iran for the first time. Seropositivity was associated with adverse pregnancy outcomes and maternal age. The pregnant women who experienced abnormal pregnancy had higher seroprevalence of C. burnetii compared to women with normal pregnancy. PMID- 27252923 TI - Intraventricular Hemorrhage in a Term Neonate: Manifestation of Protein S Deficiency- A Case Report. AB - Protein S (PS) is an antithrombotic plasma protein that plays essential roles in limiting thrombus formation in the anticoagulant system. Protein S deficiency is related with recurrent thrombosis. Here, the authors report a case of a term neonate with severe PS deficiency in year 2015, Imam Hospital, Tehran, Iran, that had seizures and intraventricular hemorrhage (IVH) since the age of 3 days. Nine month follow-up did not show any developmental problems and MRI showed no hemorrhage. PMID- 27252924 TI - Are the Public Health Centers Real Threats to Private Clinics in Korea? PMID- 27252925 TI - Determinants of Consanguinity and Inbreeding Coefficient F in Dir Lower District, North-West Pakistan: A Multivariate Approach. PMID- 27252926 TI - Drug Induced Autoimmune Hepatitis by Amoxicillin-Clavulanate. PMID- 27252927 TI - Evaluation of Therapeutic Effect of Jichuanjian on Cathartic Colon. PMID- 27252928 TI - Package of Office Exercise Training as a New Idea for Office Workers. PMID- 27252930 TI - Climate Change and its Impact on Food and Nutrition Security in Pakistan. PMID- 27252929 TI - Towards Better Understanding of OHRQoL in Edentulous Patients. PMID- 27252931 TI - A Letter to the Editor Titled "Breast Cancer among Pakistani Women" in the Iran J. Public Health (Vol. 44, No. 4, Apr 2015, pp. 586-587). PMID- 27252932 TI - The Prevalence of Yersinia Yop-Specific Iga Antibodies in Iranian Healthy Blood Donors and Evaluation of Blood Culture of Seropositive Donors. PMID- 27252933 TI - Patient Satisfaction with Community Pharmacies in Tehran, Iran; Part I. PMID- 27252934 TI - Association of some psychosocial factors with anthropometric measures in nationally representative sample of Iranian adolescents: the CASPIAN-III study. AB - BACKGROUND: During the last two decades, adolescent obesity has increased in western countries. In Iran-as a developing country- the prevalence of obesity is raised among youngsters as well. This study conducted to identify an association of adolescents' loneliness, self-confidence and relationship with others in home and school environment with their weight status. METHODS: In this cross-sectional national survey, 5682 students aged 10-18 years from urban and rural districts of 27 provinces of Iran were selected via stratified multi-stage sampling method. Data on psychological problems of students was gathered through a questionnaire. Height, weight, and waist circumferences were measured according to standard protocols. Body mass index (BMI) and waist- to-height ratio was calculated. RESULTS: Boys which did not have best friends, spend time with their friends after school or get acceptance from them, had higher BMI than others. Only girls who did not spend time with their friends had higher BMI (19.48 +/- 4.28) vs. (19.09 +/- 3.92) and WC (71.04 +/- 21.29) vs. (69.15 +/- 17.43) than others, P < 0.05. In both sexes, adolescents who had sense of pressure about doing homework or had difficulties in relationship with their parents had higher BMI and WC values. Girls who reported being victim of violent behaviors (being bullied), had lower BMI compared to others. Risk of being overweight and obese, but not abdominal obese was statistically higher in adolescents not having close friends (OR = 1.81, CI: 1.11-2.95). Lack of self-confidence increased only the risk of obesity in teens (OR = 1033, CI: 1.09-1.64). CONCLUSIONS: Our findings suggest that strategies for prevention of overweight and obesity in adolescent should be taking into account a deeper knowledge of psychosocial issues due to be able to design more effective programs for treating overweight teens. PMID- 27252935 TI - Long-term Outcomes of Childhood Onset Nephrotic Syndrome. AB - There are limited studies on long-term outcomes of childhood onset nephrotic syndrome (NS). A majority of children with NS have steroid-sensitive nephrotic syndrome (SSNS). Steroid-resistant nephrotic syndrome (SRNS) is associated with a high risk of developing end-stage renal disease. Biomarkers and analysis of genetic mutations may provide new information for prognosis in SRNS. Frequently relapsing and steroid-dependent NS is associated with long-term complications, including dyslipidemia, cataracts, osteoporosis and fractures, obesity, impaired growth, and infertility. Long-term complications of SSNS are likely to be under recognized. There remain many gaps in our knowledge of long-term outcomes of childhood NS, and further study is indicated. PMID- 27252936 TI - The BULT Method for Pediatric Minilaparoscopic Pyeloplasty in Infants: Technique and Results. AB - We reviewed retrospectively the results of transperitoneal minilaparoscopic pyeloplasty in children younger than 2 years. The surgical technique utilized as well as the retrograde placement of the stent is described in detail. Twenty-four consecutive children with a mean age of 7.9 months (range 1-23), a mean weight of 7.4 kg (range 4-12), and a mean follow-up of 18 months (range 3-59) are included. Preoperative grade of dilatation was 3.8 (SFU scale) and postoperatively improved to 1.5. The AP diameter of the pelvis decreased from a mean of 28-9 mm. In 83% of cases, there was complete resolution of hydronephrosis (grades 0-2) and the rest showed improvement. There was one conversion to open surgery in a child with a horseshoe kidney. There was one omental prolapse though a port site in a child in whom an inappropriate drain was used. There were no stent-related complications and no reinterventions for persistent or recurrent obstruction. Given these outcomes, low complication rate and excellent cosmetic results, we recommend transperitoneal minilaparoscopy with a double J stent and a perirenal drain for infants requiring pyeloplasty. PMID- 27252938 TI - Bayesian Inference on Predictors of Sex of the Baby. AB - It is well known that the sex ratio at birth is a biological constant, being about 106 boys to 100 girls. However couples have always wanted to know and decide in advance the sex of a newborn. For example, a large number of papers appeared connecting biometrical variables, such as length of follicular phase in the woman menstrual cycle or timing of intercourse acts to the sex of new baby. In this paper, we propose a Bayesian model to validate some of these theories by using an independent database. Results show that we could not show an effect of the follicular length on the sex of the baby. We also obtain a slightly larger probability, although not significant, of conceiving a female just after the mucus peak day. PMID- 27252937 TI - Thinking, Walking, Talking: Integratory Motor and Cognitive Brain Function. AB - In this article, we argue that motor and cognitive processes are functionally related and most likely share a similar evolutionary history. This is supported by clinical and neural data showing that some brain regions integrate both motor and cognitive functions. In addition, we also argue that cognitive processes coincide with complex motor output. Further, we also review data that support the converse notion that motor processes can contribute to cognitive function, as found by many rehabilitation and aerobic exercise training programs. Support is provided for motor and cognitive processes possessing dynamic bidirectional influences on each other. PMID- 27252939 TI - Biofilm Formation and Motility Depend on the Nature of the Acinetobacter baumannii Clinical Isolates. AB - Acinetobacter baumannii is a nosocomial pathogen involved in various infections ranging from minor soft-tissue infections to more severe infections such as ventilator-associated pneumonia and bacteremia. The severity and the type of infections depend on the genetic and phenotypic variations of the strains. In this study, we compared the extent of biofilm formation and motility displayed by 60 multidrug-resistant A. baumannii clinical strains isolated from blood and sputum samples from patients from Southern India. Our results showed that isolates from the sputum samples formed significantly more robust biofilm compared to the blood isolates. On the other hand, we observed that the blood isolates were more motile than the sputum isolates. To the best of our knowledge, this is the first study that systematically evaluated the correlation between these two phenotypic traits and the nature of the isolates. PMID- 27252940 TI - Plant G-Proteins Come of Age: Breaking the Bond with Animal Models. AB - G-proteins are universal signal transducers mediating many cellular responses. Plant G-protein signaling has been modeled on the well-established animal paradigm but accumulated experimental evidence indicates that G-protein-dependent signaling in plants has taken a very different evolutionary path. Here we review the differences between plant and animal G-proteins reported over past two decades. Most importantly, while in animal systems the G-protein signaling cycle is activated by seven transmembrane-spanning G-protein coupled receptors, the existence of these type of receptors in plants is highly controversial. Instead plant G-proteins have been proven to be functionally associated with atypical receptors such as the Arabidopsis RGS1 and a number of receptor-like kinases. We propose that, instead of the GTP/GDP cycle used in animals, plant G-proteins are activated/de-activated by phosphorylation/de-phosphorylation. We discuss the need of a fresh new look at these signaling molecules and provide a hypothetical model that departs from the accepted animal paradigm. PMID- 27252941 TI - The TRAPP Subunit Trs130p Interacts with the GAP Gyp6p to Mediate Ypt6p Dynamics at the Late Golgi. AB - Small GTPases of the Rab superfamily participate in virtually all vesicle mediated trafficking events. Cycling between an active GTP-bound form and an inactive GDP-bound form is accomplished in conjunction with guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs), respectively. Rab cascades have been described in which an effector of an activated Rab is a GEF for a downstream Rab, thus ensuring activation of a pathway in an ordered fashion. Much less is known concerning crosstalk between GEFs and GAPs although regulation between these factors could also contribute to the overall physiology of a cell. Here we demonstrate that a subunit of the TRAPP II multisubunit tethering factor, a Rab GEF, participates in the recruitment of Gyp6p, a GAP for the GTPase Ypt6p, to Golgi membranes. The extreme carboxy-terminal portion of the TRAPP II subunit Trs130p is required for the interaction between TRAPP II and Gyp6p. We further demonstrate that TRAPP II mutants, but not a TRAPP III mutant, display a defect in Gyp6p interaction. A consequence of this defective interaction is the enhanced localization of Ypt6p at late Golgi membranes. Although a ypt31/32 mutant also resulted in an enhanced localization of Gyp6p at the late Golgi, the effect was not as dramatic as that seen for TRAPP II mutants, nor was Ypt31/32 detected in the same TRAPP II purification that detected Gyp6p. We propose that the interaction between TRAPP II and Gyp6p represents a parallel mechanism in addition to that mediated by Ypt31/32 for the recruitment of a GAP to the appropriate membrane, and is a novel example of crosstalk between a Rab GAP and GEF. PMID- 27252942 TI - The Current and Future Treatment of Brain Metastases. AB - Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient's overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID- 27252944 TI - An Interplay among FIS, H-NS, and Guanosine Tetraphosphate Modulates Transcription of the Escherichia coli cspA Gene under Physiological Growth Conditions. AB - CspA, the most characterized member of the csp gene family of Escherichia coli, is highly expressed not only in response to cold stress, but also during the early phase of growth at 37 degrees C. Here, we investigate at molecular level the antagonistic role played by the nucleoid proteins FIS and H-NS in the regulation of cspA expression under non-stress conditions. By means of both probing experiments and immunological detection, we demonstrate in vitro the existence of binding sites for these proteins on the cspA regulatory region, in which FIS and H-NS bind simultaneously to form composite DNA-protein complexes. While the in vitro promoter activity of cspA is stimulated by FIS and repressed by H-NS, a compensatory effect is observed when both proteins are added in the transcription assay. Consistently with these findings, inactivation of fis and hns genes reversely affect the in vivo amount of cspA mRNA. In addition, by means of strains expressing a high level of the alarmone guanosine tetraphosphate ((p)ppGpp) and in vitro transcription assays, we show that the cspA promoter is sensitive to (p)ppGpp inhibition. The (p)ppGpp-mediated expression of fis and hns genes is also analyzed, thus clarifying some aspects of the regulatory loop governing cspA transcription. PMID- 27252943 TI - Dehydration and Cognition in Geriatrics: A Hydromolecular Hypothesis. AB - Dehydration is one of the ten most frequent diagnoses responsible for the hospital admission of elderly in the United States. It is associated with increased mortality, morbidity and an estimated cost of 1.14 billion per year (Xiao et al., 2004; Schlanger et al., 2010; Pretorius et al., 2013; Frangeskou et al., 2015). Older individuals are predisposed to dehydration encephalopathy as a result of decreased total body water (TBW) and diminished sensation of thirst. We hypothesize that thirst blunting in older individuals is the result of a defective microRNA-6842-3p failing to silence the expression of the vesicular GABA transporters (VGAT) and alpha 7 cholinergic nicotinic receptors in the subfornical organ (SFO) of the hypothalamus. We hypothesize further that resultant dehydration facilitates protein misfolding and aggregation, predisposing to neurocognitive disorders. We completed a search of predicted microRNA targets, utilizing the public domain tool miRDB and found that microRNA 6842-3p modulates the SLC6A1 and CHRNA7 genes both of which were previously hypothesized to inhibit the thirst sensation by their action on SFO. The primary aim of this article is to answer two questions: Can prevention and correction of dehydration in elderly lower age-related cognitive deterioration? Can exosomal miR-6842 in the peripheral blood predict dehydration encephalopathy in elderly? PMID- 27252945 TI - Altered Expression of TLR2 and TLR4 on Peripheral CD14+ Blood Monocytes in Children with Urinary Tract Infection. AB - Urinary tract infection (UTI) is the second most common bacterial infection, after otitis media, in infants and children. The mechanisms of disease susceptibility and the role of immunity in the pathogenesis of UTI in children have been evaluated. In recent years, Toll-Like Receptors (TLRs) have been recognized as specific components of the innate immune system constituting important mediators in host immune recognition. The aim of the present study was to determine TauLR2 and TLR4 expression during the acute phase of UTI in infants and children by measuring the CD14/TLR2 and CD14/TLR4 expression on monocytes. We also attempted to compare the TLRs expression with the immunological status of the patients to healthy children. The study group consisted of 60 children (36 females and 24 males) and the control group included 60 age-matched pediatric subjects (27 females and 33 males). In our study, no antibody deficiency was found either in the children with UTI or in healthy subjects. There might be a connection between low IgA, IgG, and IgG subclasses serum levels and UTI as there was a statistically significant difference between patients and healthy children. A higher expression of CD14/TLR2 was revealed in patients (90,07%) compared to controls (85,48%) as well as CD14/TLR4 in patients (90,53%) compared to controls (87,25%) (statistically significant difference, p < 0,05). The results of this study could provide new understanding of UTIs' pathogenesis in children. PMID- 27252946 TI - Free flap transfer for complex regional pain syndrome type II. AB - A patient with complex regional pain syndrome type II was successfully treated using free anterolateral thigh flap transfer with digital nerve coaptation to the cutaneous nerve of the flap. Release of the scarred tissue and soft tissue coverage with targeted sensory nerve coaptation were useful in relieving severe pain. PMID- 27252947 TI - Volar dislocation of the thumb metacarpophalangeal joint with acute repair of the ulnar collateral ligament. AB - Volar dislocations of the thumb metacarpophalangeal joint are uncommon and can be associated with rupture of the ulnar collateral ligament (UCL). We report a case where a volar thumb dislocation was successfully closed reduced, but instability required open repair of the UCL. Early motion protocol helped achieve favorable results. PMID- 27252948 TI - The bilobed flap for popliteal defect reconstruction. AB - Bilobed flaps were first introduced to close small nasal defects. We reconstructed a defect of the popliteal fossa using a random-pattern bilobed flap. We recommend the use of random-pattern bilobed flaps as a reliable technique for covering defects of the popliteal fossa. PMID- 27252949 TI - Angiofibrolipoma of the tendon sheath. AB - We present a rare case of benign tumor of the hand. PMID- 27252950 TI - Reconstruction after resection of malignant parapharyngeal space tumor. AB - Primary malignant tumor of the parapharyngeal space (PPS) is rare. After surgical resection, primary closure could be considered if the oropharynx mucosa remains. This report describes two patients who underwent reconstruction by free tissue transfer after the resection of PPS tumors. This report was presented at the 56th annual meeting of the Japanese Society of Plastic and Reconstructive Surgery, 4 April, 2013. PMID- 27252951 TI - Rapidly enlarging cutaneous nodules on a full-thickness skin graft following an excision of a squamous cell carcinoma - a diagnostic clue for multiple myeloma. AB - Cutaneous extramedullary plasmacytomas (EMPs) are rare plasma cell neoplasms of the skin occurring in 2-4% of patients with multiple myeloma (MM). We describe a man diagnosed with IgA lambda MM (Stage III) after rapidly enlarging cutaneous nodules developed in the surgical site of recently excised skin malignancies. Cutaneous EMP must be considered for expanding cutaneous nodules at sites of surgery or trauma. PMID- 27252952 TI - Endoscopic-assisted infraorbital nerve release. AB - Endoscopic-assisted techniques in plastic and craniofacial surgeries are limited. We present a patient with infraorbital nerve entrapment following traumatic facial injury that failed conservative management. Compression of the nerve was treated with an endoscopic-assisted nerve release of the surrounding soft tissue with a circumferential foraminal osteotomy. PMID- 27252953 TI - Acrometastasis to metacarpal bone disclosing an occult lung cancer. AB - The purpose of this study is to demonstrate an occulting metastatic lung cancer diagnosed by a painful mass at right hand. Under early diagnosis and meticulous treatment, this patient has been painless without local recurrence and had full hand function for 3 years. PMID- 27252954 TI - Occult moyamoya disease causing fulminant infarction after septorhinoplasty. AB - Moyamoya disease is an extremely rare cerebrovascular condition that predisposes affected patients to stroke in association with progressive stenosis of the intracranial internal carotid arteries and their proximal branches. To our knowledge, this is the first report of a lethal complication due to moyamoya disease after septorhinoplasty. A 25-year-old female Caucasian patient presented to our outpatient clinic with impaired nasal breathing for septorhinoplasty. Regrettably the patient died 6 days postoperatively due to progressive infarct series affecting all major cerebral vessels. Despite a thorough knowledge of possible local complications after septorhinoplasty, it is of utmost importance to consider rare general complications like moyamoya disease. Although cerebral infarctions are very rare in young people, it is crucial to identify and correctly interpret underlying typical symptoms. PMID- 27252955 TI - Flail extremity resulting from constriction band syndrome: Neurovascular implications and surgical management. AB - PURPOSE: Constriction band syndrome afflicting in utero development can lead to devastating and possibly fatal outcomes. A lack of consensus regarding noninvasive testing and surgical modalities is likely secondary to the continued poorly understood pathology. Methods : We provide a case report of a 6-month-old boy who presented with a functional, nonsensate upper limb after surgical release of midhumeral banding at 3 months of age. RESULTS: Exploration revealed intact, albeit atrophic, peripheral nerves with brachial artery disruption above the elbow. Sural nerve grafting was performed and 2-year follow-up demonstrated return of protective sensation in the median nerve distribution with minimal motor return. CONCLUSION: This case demonstrates that nerves present distal to the original soft tissue insult oppose the idea of failure of nerve formation. Early nerve grafting at the time of initial Z-plasty release may serve to improve long-term functional outcomes. PMID- 27252956 TI - Simultaneous closed rupture of flexor digitorum superficialis and flexor digitorum profundus tendons in the middle finger: a case report. AB - A 20-year-old man suffered a closed rupture of both flexor tendons in the middle finger while playing rugby. Primary repair of the flexor digitorum profundus and excision of the flexor digitorum superficialis was performed. At follow up he reported a Disabilities of the Arm, Shoulder and Hand score of 0 and unrestricted return to activities. PMID- 27252957 TI - A unique physeal injury of the distal phalanx. AB - An unusual Salter-Harris Type 1 fracture variant of the distal phalanx of the index finger is described. The epiphysis was dislocated, sitting dorsally over the middle phalanx head with the articular surface facing dorsal. Reduction could only be achieved through an open procedure. The reduction was stable without supplemental fixation. PMID- 27252958 TI - A novel use for suture button suspension: reconstruction of the dorsal ulnar ligament to treat thumb metacarpal dislocation. AB - There are numerous treatment algorithms that have been developed to treat thumb carpometacarpal (CMC) arthritis. A newer treatment option for these patients is CMC stabilization using suture button suspensionplasty. The authors of this case report have extensive experience with the suture-button suspensionplasty using the Mini TightRope CMC technique (Arthrex). We present a novel usage of the suture-button suspensionplasty to reconstruct the dorsal ulnar ligament (in contrast to the usual reconstruction of the volar beak ligament) to treat a patient with persistent thumb metacarpal dislocation at the CMC joint. Two separate patients are presented. One patient demonstrates volar beak ligament instability, and the other demonstrates dorsal ulnar ligament instability. Both patients' demographics and operative indications are described. The operative technique for the novel usage of the suture-button suspensionplasty is described. Operative results of the dorsal ulnar ligament reconstruction are reviewed. After suture-button suspension of the thumb metacarpal to the trapezium, the dorsal ulnar ligament has been reconstructed. The patient demonstrated stability of the thumb CMC joint without dorsal or radial dislocation. The authors of this case report present a novel usage of the suture-button suspensionplasty to treat a patient with proximal thumb metacarpal dislocation at the trapezial-metacarpal interface. This method, in contrast to the referenced method of volar beak ligament reconstruction, allows reconstruction of the dorsal ulnar ligament. This allows stabilization of the joint by preventing dorsal and radial dislocation of the metacarpal. PMID- 27252959 TI - Correction of thumb angulations after physiolysis of delta phalanges in a child with Rubinstein-Taybi syndrome: a case report. AB - Resection of the midzone of the continuous epiphysis of a delta phalanx (physiolysis) and its replacement by a free-fat graft from local tissue was performed to improve severe radial angulation of the both thumbs in a 22-month old child with Rubinstein-Taybi syndrome. Fifty-two months after surgery, satisfactory results were obtained for pinch function, appearance, and radiographic findings. Previous reports have indicated that corrective osteotomy of the thumbs in Rubinstein-Taybi syndrome has an associated risk of incomplete correction and >30% of recurrence, because severe preoperative deformities of the delta phalanx make angulatory osteotomies difficult. Additionally, physiolysis is a less invasive procedure than corrective osteotomy and offers a reduced risk of incomplete or excess correction, physeal injury, or osteonecrosis in younger children. Therefore, physiolysis appears to be useful as an initial means of correcting severe thumb angulations secondary to a delta phalanx. We reported a case in which the physiolysis of the delta phalanx significantly improved severe angular deformities of the thumbs in association with Rubinstein-Taybi syndrome. PMID- 27252960 TI - Dermatofibrosarcoma protuberans, a rare but locally aggressive tumor on finger: clinical and aeromedical considerations. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare, slow growing, locally infiltrative tumor of intermediate malignancy. It is mostly found on the trunk and head, rarely on hands. The course of evaluation and treatment of a young pilot with DFSP on left middle finger is reported. The clinical issues and aeromedical considerations of this rare tumor is discussed. PMID- 27252961 TI - Osteoid osteoma of the lunatum mimicking Kienbock's disease. AB - Hands, especially lunatum, are involved very rarely with osteoid osteoma. This report presents an osteoid osteoma of the lunatum, which was previously misdiagnosed as Kienbock's disease and had undergone surgery. Magnetic resonance imaging may lead the clinician to misdiagnose because of the excessive bone edema around the carpus. The operation should be planned according to radiography and computed tomography findings. PMID- 27252962 TI - Neglected lunate dislocation presenting as carpal tunnel syndrome. AB - Most of carpal tunnel syndrome cases are idiopathic, and secondary causes are so rare that can be easily missed. We present a patient with neglected undiagnosed lunate dislocation compressing on median nerve causing its signs and symptoms. PMID- 27252963 TI - Combined therapy of NPWT and bipedicled flap as an alternative approach for giant abdominal wall defect with significant visceral edema: report of a case. AB - Open abdomen management is commonly used for the critically injured patients to avoid abdominal compartment syndrome. But it usually continues for days to weeks and finally results in abdominal wall defect that is too wide to close at once. This article presents an alternative approach to close the giant abdominal wall defect by using the combination of bipedicled flaps with the components separation technique and V.A.C.(r) system. PMID- 27252964 TI - Carpal tunnel syndrome caused by vascular nerve impairment treated with open release of the carpal tunnel. AB - We present a patient suffering from classical unilateral symptoms of carpal tunnel syndrome, where the results of electrophysiological examinations were negative. Ultrasound showed at pulsatile median artery that led to direct mechanical impact on the median nerve. The patient was successfully treated with open release of the carpal tunnel. PMID- 27252965 TI - Localized lipomatosis of the perineum in a 58-year-old male patient - case report. AB - Lipomatosis of the perineum is an extremely rare condition. We report a localized hypertrophy of adipose tissue of the perineum in a 58-year-old man. The cause of enlargement could not be revealed. Nonetheless, preoperative workup and exclusion of possible malign tumors is essential. PMID- 27252966 TI - Anteromedial thigh perforator flap to cover the inguinal region in a crossover femorofemoral bypass. AB - We report the case of a 48-year-old male with an exposition of a femorofemoral crossover bypass in the inguinal region and superficial femoral occlusion. This was successfully treated using an anteromedial thigh (AMT) pedicled flap based on the perforator vessel of the descending branch of the lateral circumflex femoral artery. Our report focuses on: i) considering the AMT flap as a safe and easy option to cover the inguinal region in cases of bypass exposure; ii) describing the attachment of this flap to the deep femoral artery in a patient with superficial femoral occlusion, in spite of some literature controversy. PMID- 27252967 TI - A case of combined soft tissue and intraosseous venous malformation of the thumb treated with sclerotherapy using a bone marrow aspiration needle. AB - Vascular malformations of bone are complex lesions that can cause deformity and pain. A combined soft tissue and intraosseous venous malformation of the left thumb in a girl was treated with two sessions of ethanol sclerotherapy using a bone marrow aspiration needle under fluoroscopic guidance. PMID- 27252968 TI - Avascular necrosis of the distal pole of the scaphoid. AB - Avascular necrosis (AVN) of the scaphoid predominantly occurs in the proximal pole. Review of the literature revealed only six cases and all are suspect due to the lack of either MRI investigation or investigation of bleeding preoperatively. We report four new cases and one of them appears to be a real distal pole AVN of the scaphoid in the literature. PMID- 27252969 TI - New option for surgical treatment of the trapeziometacarpal osteoarthritis: a case report. AB - We present the case of a 71-year-old, left-handed woman with left thumb carpometacarpal (CMC) joint arthritis. The patient had no pain and could use the hand actively in daily life with a new option of surgical treatment, a vascularized pedicled third CMC joint transfer to the thumb CMC joint. PMID- 27252970 TI - A Japanese family with popliteal pterygium syndrome. AB - We investigated a family in which the mother and a daughter suffered from popliteal pterygium syndrome (PPS). Mutation in the interferon regulatory factor 6 (IRF6) gene was detected in the mother and daughter. This is the second report of a family case with mutation in the IRF6 gene in Japanese patients with PPS. PMID- 27252972 TI - The surgical treatment of familial cylindromatosis through subgaleal scalp excision. AB - We treated a 65-year-old woman with familial cylindromatosis, with cylindromas covering the entire scalp. Subgaleal tumor excision and split skin grafting was performed. The graft take was deemed to be excellent, with almost 100% coverage 2.5 weeks after operation, no complications and a satisfying esthetic result. PMID- 27252971 TI - Symmetrical peripheral gangrene caused by septic shock. AB - We report three cases of symmetrical peripheral gangrene (SPG) caused by septic shock. Most of sepsis survivors with SPG require amputation of the affected extremities. To preserve the length of the thumb and fingers, we performed surgical amputation and used flaps to cover the amputated peripheral extremities. PMID- 27252973 TI - Thrombosed vascular malformation within the flexor tendon sheath of the index finger in the palm. AB - Vascular malformations are relatively infrequent among benign lesions of the hand. We report the case of an arteriovenous malformation in a 48-year-old white woman presenting a mass in her left hand without any symptoms. The diagnosis was confirmed by histopathology and the lesion completely removed by surgery. PMID- 27252974 TI - Two case reports with literature review of the EEC syndrome: Clinical presentation and management. AB - We report on siblings who suffer from EEC syndrome and show our experiences of the "Basel concept" of cleft lip/palate repair based on the early, one-stage closure of all components. It is performed in the age of 3-4 months to provide early normal conditions for anatomy and muscle function. PMID- 27252975 TI - Restoration of oral competence in double free flap reconstructions of massive lower facial defects with fascia lata slings - Case series and review of the literature. AB - Restoration of adequate oral competence is especially challenging in double free flap reconstructions of massive head and neck defects resulting from composite resections. Our report illustrates that oral competence in double free flap reconstructions of extensive oromandibular defects can be successfully restored with tensor fascia lata suspension slings. PMID- 27252976 TI - Use of a pedicled fillet foot flap for knee preservation in severe lower extremity trauma: A case report and literature review. AB - We report the sequential use of a pedicled fillet foot flap in a clinical case of complex bilateral lower extremity trauma to achieve stable wound closure, maximizing length preservation and gait rehabilitation. In addition, we perform a literature review of the use of fillet foot flaps in lower extremity trauma. PMID- 27252977 TI - Reconstruction of a subtotally amputated auricle with a very narrow inferior pedicle. AB - In our case study, the left ear of a 57-year-old male patient was subtotally amputated due to an iron-plate cutting accident. Only a 5-mm inferior skin pedicle connected the amputated ear to the lobule. The ear was reattached with primary suture without microsurgery. The reattached ear healed uneventfully. PMID- 27252978 TI - Episode of massive pulmonary embolism after bilateral breast augmentation. AB - Pulmonary embolism is a rare postsurgical complication, even more so following breast augmentation. Herein we present a case of a 23-year-old woman who survived an episode of massive pulmonary embolism after breast implant surgery. Current literature about this subject is very scarce. PMID- 27252979 TI - "More than skin deep": Recurrent primary hand abscesses in a warehouse operative. AB - A 25-year-old male right-hand dominant warehouse operator presented with two hand infections within 12 weeks both requiring surgical drainage and antimicrobial therapy. Subsequent testing confirmed Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA). This case highlights the need for prompt multidisciplinary management of hand infections to consider, diagnose and manage atypical infections. PMID- 27252980 TI - Intestinal obstruction following harvest of VRAM-flap for reconstruction of a large perineal defect. AB - A patient with locally advanced adenocarcinoma of the rectum was operated with abdominoperineal resection and perineal reconstruction with a vertical rectus abdominis musculocutaneous flap. Six days postoperatively, there was herniation of the small bowel, between the anterior and posterior rectus sheaths, to a subcutaneous location. PMID- 27252981 TI - A dataset for assessing temporal changes in gene expression during the aging process of adult Drosophila melanogaster. AB - A Drosophila melanogaster genome-wide transcriptome dataset is available for studies on temporal patterns of gene expression. Gene expression was measured using two-dye color oligonucleotide arrays derived from Version 2 of the Drosophila Genomics Resource Center. A total of 15,158 oligonucleotide probes corresponded to a high proportion of the coding genes in the genome. The source of the flies was a highly genetically heterogeneous population maintained in an overlapping generation population regime. This regime was designed to maintain life history traits so that they were similar to those found in natural populations. Flies collected for the cohorts were obtained in a short period of time in a carefully controlled manner before virgin females and males were allowed to mate. Mated females were introduced into two large population cages in unusually high numbers (approximately 12,000 per cage) for a Drosophila laboratory longevity study. Samples were taken weekly from each cohort for 11 weeks; only a small proportion of surviving flies were present at the last two collection time points and thus they were exceptionally old compared to those collected in early-to-midlife samples. The data set is useful for studies of temporal patterns of gene expression as flies age. The very large size of each cohort, and relatively frequent incidence of temporal samples, allows for a fine scale study of gene expression from young to very old flies. PMID- 27252982 TI - Sagittal balance is more than just alignment: why PJK remains an unresolved problem. AB - BACKGROUND: The durability of adult spinal deformity surgery remains problematic. Revision rates above 20 % have been reported, with a range of causes including wound infection, nonunion and adjacent level pathology. While some of these complications have been amenable to changes in patient selection or surgical technique, Proximal Junctional Kyphosis (PJK) remains an unresolved challenge. This study examines the contributions of non-mechanical factors to the incidence of postoperative sagittal imbalance and PJK after adult deformity surgery. METHODS: We reviewed a consecutive series of adult spinal deformity patients who required revision for PJK from 2013 to 2015 and examined in their medical records in detail. RESULTS: Neurologic disorders were identified in 22 (76 %) of the 29 PJK cases reviewed in this series. Neurologic disorders included Parkinson's disease (1), prior stroke (5), metabolic encephalopathy (2), seizure disorder (1), cervical myelopathy (7), thoracic myelopathy (1), diabetic neuropathy (5) and other neuropathy (4). Other potential comorbidities affecting standing balance included untreated cataracts (9), glaucoma (1) and polymyositis (1). Eight patients were documented to have frequent falls, with twelve cases having a fall right before symptoms related to the PJK were noted. CONCLUSION: PJK is an important contributing factor to the substantial and unsustainable rate of revision surgery following adult deformity correction. Multiple efforts to avoid PJK via alterations in surgical technique have been largely unsuccessful. This study suggests that non-mechanical neuromuscular co-morbidities play an important role in post-operative sagittal imbalance and PJK. Recognizing the multi factorial etiology of PJK may lead to more successful strategies to avoid PJK and improve surgical outcomes. PMID- 27252983 TI - Scoliosis and Spinal Disorders journal: a new, cutting-edge frontier in spine publishing. PMID- 27252984 TI - Adolescent idiopathic scoliosis (AIS): a multifactorial cascade concept for pathogenesis and embryonic origin. AB - This paper formulates a novel multifactorial Cascade Concept for the pathogenesis of adolescent idiopathic scoliosis (AIS). This Concept stems from the longitudinal findings of Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) who identified leptin body composition factors at 10 years of age associated with a scoliosis deformity found at 15 years. We interpret these findings in the light of some concepts for AIS pathogenesis. In particular, we speculate that the leptin body composition effect is linked to central nervous system development and the initiation of the asynchronous neuro-osseous growth mechanism that involves the creation of a neuraxis tether of relative anterior vertebral overgrowth. The latter mechanism in combination with age and gender-related anatomical variants of vertebral backward tilt (dorsal shear concept), human upright posture, adolescent growth factors, Hueter-Volkmann effect in vertebrae and vertebral bone mass abnormalities, lead to AIS, possibly both initiation and progression of scoliosis curvatures. Being multifactorial, while the Cascade Concept cannot be tested for all its components, some components should be testable by the method of numerical simulation. Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) also suggested the origin of scoliosis was in the embryonic stages of life from cell types, including adipocytes and osteoblasts, derived from the same progenitor cells, and myoblasts from mesodermal somites. The involvement of cell types from different developmental origins suggests a process acting in embryonic life at a similar time, probably environmental, as previously proposed from anthropometric studies. As a Complex disease, AIS will involve genetic, environmental and life style factors operating in development and growth; this possibility needs evaluating in epidemiological studies. PMID- 27252986 TI - Brivaracetam: new compound approved for the treatment of epilepsy. AB - Brivaracetam was approved in the E.U. and U.S. at the beginning of 2016 for the adjunctive treatment of focal epilepsies in patients over 16 years of age. This compound is a novel high-affinity synaptic vesicle glycoprotein 2A (SV2A) ligand, with a selectivity for this protein that is 10- to 30-fold higher than that shown by levetiracetam. Preclinical studies show that brivaracetam might have a stronger anticonvulsant effect and distributes in the brain more quickly, when compared to levetiracetam. The agent has linear and simple pharmacokinetics and a low interaction potential. Six double-blind placebo-controlled studies have assessed doses from 5 to 200 mg/day. Significant efficacy has been observed from doses of 50 mg/day, but there was not a clear dose-effect relationship. Short term tolerability was excellent with all doses. Adverse events significantly associated with brivaracetam were dizziness, somnolence, fatigue and irritability. An excellent tolerability profile has been found after administration of a formulation for intravenous use. PMID- 27252985 TI - Is lumbar facet joint tropism developmental or secondary to degeneration? An international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium. AB - BACKGROUND: Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether tropism is a pre-existing developmental phenomena or secondary to progressive remodeling of the joint structure due to degenerative changes. As such, the following study addressed the occurrence of tropism of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. METHODS: An international, multi-center cross-sectional study that consisted of 349 patients with single level DS recruited from 33 spine institutes in the Asia Pacific region was performed. Axial MRI/CT from L3-S1 were utilized to assess left and right facet joint sagittal angulation in relation to the coronal plane. The angulation difference between the bilateral facets was obtained. Tropism was noted if there was 8 degrees or greater angulation difference between the facet joints. Tropism was noted at levels of DS and compared to immediate adjacent and distal non-DS levels, if applicable, to the index level. Age, sex-type and body mass index (BMI) were also noted and assessed in relation to tropism. RESULTS: Of the 349 subjects, there were 63.0 % females, the mean age was 61.8 years and the mean BMI was 25.6 kg/m(2). Overall, 9.7, 76.5 and 13.8 % had L3-L4, L4-L5 and L5-S1 DS, respectively. Tropism was present in 47.1, 50.6 and 31.3 % of L3-L4, L4-L5 and L5-S1 of levels with DS, respectively. Tropism involved 33.3 to 50.0 % and 33.3 to 58.8 % of the immediate adjacent and most distal non-DS levels from the DS level, respectively. Patient demographics were not found to be significantly related to tropism at any level (p > 0.05). CONCLUSIONS: To the authors' knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing facet joint tropism. Although levels with DS were noted to have tropism, immediate adjacent and distal levels with no DS also exhibited tropism, and were not related to age and other patient demographics. This study suggests that facet joint tropism or perhaps subsets of facet joint orientation may have a pre-disposed orientation that may be developmental in origin or a combination with secondary changes due to degenerative/slip effects. The presence of tropism should be noted in all imaging assessments, which may have implications in treatment decision-making, prognostication of disease progression, and predictive modeling. Having a deeper understanding of such concepts may further elaborate on the precision phenotyping of the facets and their role in more personalized spine care. Additional prospective and controlled studies are needed to further validate the findings. PMID- 27252988 TI - Memantine and donepezil: a fixed drug combination for the treatment of moderate to severe Alzheimer's dementia. AB - Donepezil (and other cholinesterase inhibitors [ChEIs]) and memantine are the mainstays of treatment in Alzheimer's dementia, addressing respectively, the cholinergic and glutamatergic dysregulation which underlies or results from its pathophysiology. To alleviate the pill burden and swallowing difficulties associated with the condition, a fixed drug combination of extended-release memantine and donepezil was developed. This combination was shown to be both bioequivalent to the components administered separately and could be administered sprinkled over soft food. The mode of action, pharmacokinetics, clinical efficacy and safety and tolerability of the combination are discussed together with the wider, often conflicting trial literature of combination versus monotherapy with memantine and ChEIs, their meta-analyses and treatment guidelines. PMID- 27252987 TI - Lumacaftor/ivacaftor combination for cystic fibrosis patients homozygous for Phe508del-CFTR. AB - Cystic fibrosis (CF) is a life-shortening inherited disease caused by the loss or dysfunction of the CF transmembrane conductance regulator (CFTR) channel activity resulting from mutations in the CFTR gene. Phe508del is the most prevalent mutation, with approximately 90% of all CF patients carrying it on at least one allele. Over the past two or three decades, significant progress has been made in understanding the pathogenesis of CF, and in the development of effective CF therapies. The approval of Orkambi(r) (lumacaftor/ivacaftor) marks another milestone in CF therapeutics development, which, with the advent of personalized medicine, could potentially revolutionize CF care and management. This article reviews the rationale, progress and future direction in the development of lumacaftor/ivacaftor combination to treat CF patients homozygous for the Phe508del-CFTR mutation. PMID- 27252989 TI - Venetoclax: Bcl-2 inhibition for the treatment of chronic lymphocytic leukemia. AB - Venetoclax (ABT-199) is a small-molecule selective oral inhibitor of the antiapoptotic protein Bcl-2 that promotes programmed cell death of chronic lymphocytic leukemia (CLL) cells regulating the release of proapoptotic factors, such as Smac/Diablo, apoptosis-inducing factor (AIF) and cytochrome c. In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax for patients diagnosed with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. This review will focus on the mechanism of action, preclinical studies and clinical development of venetoclax both as a monotherapy and in combination with other drugs for CLL in the current milieu of therapy dominated by novel tyrosine kinase inhibitors such as ibrutinib and idelalisib. PMID- 27252990 TI - European Association of Urology--31st Annual Congress (March 11-15, 2016--Munich, Germany). AB - The 31st Annual European Association of Urology (EAU) Congress held in Munich, Germany, was a platform for expert urological specialists from all over the world to find a unique space to share their evidence-based knowledge during state-of the art lectures, presentations and courses. This report covers selected presentations covering cancer-related presentations. PMID- 27252992 TI - Reply. PMID- 27252991 TI - Genomic imprinting defect in Zfp57 mutant iPS cell lines. AB - ZFP57 maintains genomic imprinting in mouse embryos and ES cells. To test its roles during iPS reprogramming,we derived iPS clones by utilizing retroviral infection to express reprogramming factors in mouse MEF cells. After analyzing four imprinted regions, we found that parentally derived DNA methylation imprint was largely maintained in the iPS clones with Zfp57 but missing in those without maternal or zygotic Zfp57. Intriguingly, DNA methylation imprint was lost at the Peg1 and Peg3 but retained at the Snrpn and Dlk1-Dio3 imprinted regions in the iPS clones without zygotic Zfp57. This finding will be pursued in future studies. PMID- 27252993 TI - [Diagnosis and treatment guideline on drug-induced liver injury]. PMID- 27253039 TI - The clinical utility of molecular genetic cancer profiling. AB - INTRODUCTION: Next-Generation-Sequencing (NGS) has enabled gene mutation profiling - cataloguing sequence variants and modifications in clinical assays encompassing tens to thousands of genes in tumors and in germlines. The clinical benefit of applying multi-gene NGS to diverse applications in various malignancies remains to be demonstrated. AREAS COVERED: Applications of gene mutation profiling in oncology include screening cancer-prone families, classification of malignancies, treatment selection, and monitoring the response to treatment of solid tumors (the 'liquid biopsy'). Google Scholar was used to search PubMed for the period 2011-2016 using combinations of the following search terms: 'clinical utility', NGS, 'molecular diagnostics'. Expert commentary: Clinical studies are in progress pairing mutation profiling with streamlined new trial designs to speed identification of promising drug-target combinations and to see if genotype-informed treatment selection will improve outcome across a spectrum of histologies. The analytical advantages and falling cost of NGS make focused gene panels likely to become the dominant modality in molecular diagnostic testing even if trials eventually discourage use of large panels to test all malignancies. PMID- 27253040 TI - Simultaneous Selective-Area and Vapor-Liquid-Solid Growth of InP Nanowire Arrays. AB - Selective-area epitaxy is highly successful in producing application-ready size homogeneous arrays of III-V nanowires without the need to use metal catalysts. Previous works have demonstrated excellent control of nanowire properties but the growth mechanisms remain rather unclear. Herein, we report a detailed growth study revealing that fundamental growth mechanisms of pure wurtzite InP ?111?A nanowires can indeed differ significantly from the simple picture of a facet limited selective-area growth process. A dual growth regime with and without metallic droplet is found to coexist under the same growth conditions for different diameter nanowires. Incubation times and highly nonmonotonous growth rate behaviors are revealed and explained within a dedicated kinetic model. PMID- 27253059 TI - Mechanism of B-box 2 domain-mediated higher-order assembly of the retroviral restriction factor TRIM5alpha. AB - Restriction factors and pattern recognition receptors are important components of intrinsic cellular defenses against viral infection. Mammalian TRIM5alpha proteins are restriction factors and receptors that target the capsid cores of retroviruses and activate ubiquitin-dependent antiviral responses upon capsid recognition. Here, we report crystallographic and functional studies of the TRIM5alpha B-box 2 domain, which mediates higher-order assembly of TRIM5 proteins. The B-box can form both dimers and trimers, and the trimers can link multiple TRIM5alpha proteins into a hexagonal net that matches the lattice arrangement of capsid subunits and enables avid capsid binding. Two modes of conformational flexibility allow TRIM5alpha to accommodate the variable curvature of retroviral capsids. B-box mediated interactions also modulate TRIM5alpha's E3 ubiquitin ligase activity, by stereochemically restricting how the N-terminal RING domain can dimerize. Overall, these studies define important molecular details of cellular recognition of retroviruses, and how recognition links to downstream processes to disable the virus. PMID- 27253060 TI - Complexin induces a conformational change at the membrane-proximal C-terminal end of the SNARE complex. AB - Complexin regulates spontaneous and activates Ca(2+)-triggered neurotransmitter release, yet the molecular mechanisms are still unclear. Here we performed single molecule fluorescence resonance energy transfer experiments and uncovered two conformations of complexin-1 bound to the ternary SNARE complex. In the cis conformation, complexin-1 induces a conformational change at the membrane proximal C-terminal end of the ternary SNARE complex that specifically depends on the N-terminal, accessory, and central domains of complexin-1. The complexin-1 induced conformation of the ternary SNARE complex may be related to a conformation that is juxtaposing the synaptic vesicle and plasma membranes. In the trans conformation, complexin-1 can simultaneously interact with a ternary SNARE complex via the central domain and a binary SNARE complex consisting of syntaxin-1A and SNAP-25A via the accessory domain. The cis conformation may be involved in activation of synchronous neurotransmitter release, whereas both conformations may be involved in regulating spontaneous release. PMID- 27253061 TI - CELF RNA binding proteins promote axon regeneration in C. elegans and mammals through alternative splicing of Syntaxins. AB - Axon injury triggers dramatic changes in gene expression. While transcriptional regulation of injury-induced gene expression is widely studied, less is known about the roles of RNA binding proteins (RBPs) in post-transcriptional regulation during axon regeneration. In C. elegans the CELF (CUGBP and Etr-3 Like Factor) family RBP UNC-75 is required for axon regeneration. Using crosslinking immunoprecipitation coupled with deep sequencing (CLIP-seq) we identify a set of genes involved in synaptic transmission as mRNA targets of UNC-75. In particular, we show that UNC-75 regulates alternative splicing of two mRNA isoforms of the SNARE Syntaxin/unc-64. In C. elegans mutants lacking unc-75 or its targets, regenerating axons form growth cones, yet are deficient in extension. Extending these findings to mammalian axon regeneration, we show that mouse Celf2 expression is upregulated after peripheral nerve injury and that Celf2 mutant mice are defective in axon regeneration. Further, mRNAs for several Syntaxins show CELF2 dependent regulation. Our data delineate a post-transcriptional regulatory pathway with a conserved role in regenerative axon extension. PMID- 27253062 TI - Testing the Munch hypothesis of long distance phloem transport in plants. AB - Long distance transport in plants occurs in sieve tubes of the phloem. The pressure flow hypothesis introduced by Ernst Munch in 1930 describes a mechanism of osmotically generated pressure differentials that are supposed to drive the movement of sugars and other solutes in the phloem, but this hypothesis has long faced major challenges. The key issue is whether the conductance of sieve tubes, including sieve plate pores, is sufficient to allow pressure flow. We show that with increasing distance between source and sink, sieve tube conductivity and turgor increases dramatically in Ipomoea nil. Our results provide strong support for the Munch hypothesis, while providing new tools for the investigation of one of the least understood plant tissues. PMID- 27253063 TI - ELKS controls the pool of readily releasable vesicles at excitatory synapses through its N-terminal coiled-coil domains. AB - In a presynaptic nerve terminal, synaptic strength is determined by the pool of readily releasable vesicles (RRP) and the probability of release (P) of each RRP vesicle. These parameters are controlled at the active zone and vary across synapses, but how such synapse specific control is achieved is not understood. ELKS proteins are enriched at vertebrate active zones and enhance P at inhibitory hippocampal synapses, but ELKS functions at excitatory synapses are not known. Studying conditional knockout mice for ELKS, we find that ELKS enhances the RRP at excitatory synapses without affecting P. Surprisingly, ELKS C-terminal sequences, which interact with RIM, are dispensable for RRP enhancement. Instead, the N-terminal ELKS coiled-coil domains that bind to Liprin-alpha and Bassoon are necessary to control RRP. Thus, ELKS removal has differential, synapse-specific effects on RRP and P, and our findings establish important roles for ELKS N terminal domains in synaptic vesicle priming. PMID- 27253064 TI - MiniCORVET is a Vps8-containing early endosomal tether in Drosophila. AB - Yeast studies identified two heterohexameric tethering complexes, which consist of 4 shared (Vps11, Vps16, Vps18 and Vps33) and 2 specific subunits: Vps3 and Vps8 (CORVET) versus Vps39 and Vps41 (HOPS). CORVET is an early and HOPS is a late endosomal tether. The function of HOPS is well known in animal cells, while CORVET is poorly characterized. Here we show that Drosophila Vps8 is highly expressed in hemocytes and nephrocytes, and localizes to early endosomes despite the lack of a clear Vps3 homolog. We find that Vps8 forms a complex and acts together with Vps16A, Dor/Vps18 and Car/Vps33A, and loss of any of these proteins leads to fragmentation of endosomes. Surprisingly, Vps11 deletion causes enlargement of endosomes, similar to loss of the HOPS-specific subunits Vps39 and Lt/Vps41. We thus identify a 4 subunit-containing miniCORVET complex as an unconventional early endosomal tether in Drosophila. PMID- 27253065 TI - Kinetics of initiating polypeptide elongation in an IRES-dependent system. AB - The intergenic IRES of Cricket Paralysis Virus (CrPV-IRES) forms a tight complex with 80S ribosomes capable of initiating the cell-free synthesis of complete proteins in the absence of initiation factors. Such synthesis raises the question of what effect the necessary IRES dissociation from the tRNA binding sites, and ultimately from all of the ribosome, has on the rates of initial peptide elongation steps as nascent peptide is formed. Here we report the first results measuring rates of reaction for the initial cycles of IRES-dependent elongation. Our results demonstrate that 1) the first two cycles of elongation proceed much more slowly than subsequent cycles, 2) these reduced rates arise from slow pseudo translocation and translocation steps, and 3) the retarding effect of ribosome bound IRES on protein synthesis is largely overcome following translocation of tripeptidyl-tRNA. Our results also provide a straightforward approach to detailed mechanistic characterization of many aspects of eukaryotic polypeptide elongation. PMID- 27253066 TI - Multi-step coordination of telomerase recruitment in fission yeast through two coupled telomere-telomerase interfaces. AB - Tightly controlled recruitment of telomerase, a low-abundance enzyme, to telomeres is essential for regulated telomere synthesis. Recent studies in human cells revealed that a patch of amino acids in the shelterin component TPP1, called the TEL-patch, is essential for recruiting telomerase to telomeres. However, how TEL-patch-telomerase interaction integrates into the overall orchestration of telomerase regulation at telomeres is unclear. In fission yeast, Tel1(ATM)/Rad3(ATR)-mediated phosphorylation of shelterin component Ccq1 during late S phase is involved in telomerase recruitment through promoting the binding of Ccq1 to a telomerase accessory protein Est1. Here, we identify the TEL-patch in Tpz1(TPP1), mutations of which lead to decreased telomeric association of telomerase, similar to the phosphorylation-defective Ccq1. Furthermore, we find that telomerase action at telomeres requires formation and resolution of an intermediate state, in which the cell cycle-dependent Ccq1-Est1 interaction is coupled to the TEL-patch-Trt1 interaction, to achieve temporally regulated telomerase elongation of telomeres. PMID- 27253067 TI - Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body beta-hydroxybutyrate. AB - Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite beta-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of beta-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnf expression were observed after direct ventricular application of beta-hydroxybutyrate. Electrophysiological measurements indicate that beta-hydroxybutyrate causes an increase in neurotransmitter release, which is dependent upon the TrkB receptor. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF. PMID- 27253070 TI - Review Article: Influenza Transmission on Aircraft: A Systematic Literature Review. AB - BACKGROUND: Air travel is associated with the spread of influenza through infected passengers and potentially through in-flight transmission. Contact tracing after exposure to influenza is not performed systematically. We performed a systematic literature review to evaluate the evidence for influenza transmission aboard aircraft. METHODS: Using PubMed and EMBASE databases, we identified and critically appraised identified records to assess the evidence of such transmission to passengers seated in close proximity to the index cases. We also developed a bias assessment tool to evaluate the quality of evidence provided in the retrieved studies. RESULTS: We identified 14 peer-reviewed publications describing contact tracing of passengers after possible exposure to influenza virus aboard an aircraft. Contact tracing during the initial phase of the influenza A(H1N1)pdm09 pandemic was described in 11 publications. The studies describe the follow-up of 2,165 (51%) of 4,252 traceable passengers. Altogether, 163 secondary cases were identified resulting in an overall secondary attack rate among traced passengers of 7.5%. Of these secondary cases, 68 (42%) were seated within two rows of the index case. CONCLUSION: We found an overall moderate quality of evidence for transmission of influenza virus aboard an aircraft. The major limiting factor was the comparability of the studies. A majority of secondary cases was identified at a greater distance than two rows from the index case. A standardized approach for initiating, conducting, and reporting contact tracing could help to increase the evidence base for better assessing influenza transmission aboard aircraft. PMID- 27253069 TI - A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro. AB - Fusion of mitochondrial outer membranes is crucial for proper organelle function and involves large GTPases called mitofusins. The discrete steps that allow mitochondria to attach to one another and merge their outer membranes are unknown. By combining an in vitro mitochondrial fusion assay with electron cryo tomography (cryo-ET), we visualize the junction between attached mitochondria isolated from Saccharomyces cerevisiae and observe complexes that mediate this attachment. We find that cycles of GTP hydrolysis induce progressive formation of a docking ring structure around extended areas of contact. Further GTP hydrolysis triggers local outer membrane fusion at the periphery of the contact region. These findings unravel key features of mitofusin-dependent fusion of outer membranes and constitute an important advance in our understanding of how mitochondria connect and merge. PMID- 27253068 TI - Primate TRIM5 proteins form hexagonal nets on HIV-1 capsids. AB - TRIM5 proteins are restriction factors that block retroviral infections by binding viral capsids and preventing reverse transcription. Capsid recognition is mediated by C-terminal domains on TRIM5alpha (SPRY) or TRIMCyp (cyclophilin A), which interact weakly with capsids. Efficient capsid recognition also requires the conserved N-terminal tripartite motifs (TRIM), which mediate oligomerization and create avidity effects. To characterize how TRIM5 proteins recognize viral capsids, we developed methods for isolating native recombinant TRIM5 proteins and purifying stable HIV-1 capsids. Biochemical and EM analyses revealed that TRIM5 proteins assembled into hexagonal nets, both alone and on capsid surfaces. These nets comprised open hexameric rings, with the SPRY domains centered on the edges and the B-box and RING domains at the vertices. Thus, the principles of hexagonal TRIM5 assembly and capsid pattern recognition are conserved across primates, allowing TRIM5 assemblies to maintain the conformational plasticity necessary to recognize divergent and pleomorphic retroviral capsids. PMID- 27253072 TI - Invisibly Disabled. PMID- 27253071 TI - Traumatic Brain Injury Imaging in the Second Near-Infrared Window with a Molecular Fluorophore. AB - Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. A bright, renal-excreted, and biocompatible near-infrared II fluorophore for in vivo imaging of TBI is designed. A transient hypoperfusion in the injured cerebral region, followed by fluorophore leakage, is observed. NIR-II fluorophores can provide noninvasive assessment of TBI. PMID- 27253073 TI - Features of Prolonged Grief Symptoms in Chinese and Swiss Bereaved Parents. AB - This study investigates clinical expressions of prolonged grief in samples of 32 Chinese and 33 Swiss bereaved parents, according to the proposed International Classification of Diseases, 11th Revision model of prolonged grief disorder (PGD). Sex differences and predictors (cultural attitudes, sense of coherence, and posttraumatic growth) of PGD were analyzed. In result, after controlling for sociodemographic and loss-related sample differences, both samples showed similar PGD symptom profiles, with Swiss parents exhibiting more severe grief-related preoccupation and Chinese parents exhibiting some accessory symptoms and functional impairment to a greater extent. Multivariate analyses revealed for the Chinese sample primary predictions of PGD by life satisfaction, general health and one's world view (social cynicism) and for the Swiss sample by female sex, sense of coherence, and life satisfaction. The findings substantiate the basic appropriateness of the International Classification of Diseases, 11th Revision PGD in distinct cultural groups and may contribute to a better understanding of grief expression and its potential predictors across different cultures. PMID- 27253074 TI - Audiologic Outcomes in Ehlers-Danlos Syndrome. AB - OBJECTIVE: The focus of this study was to evaluate the prevalence, type, and severity of hearing impairment in patients with Ehlers-Danlos Syndrome (EDS) and to compare these characteristics with patient demographics and other otologic factors. STUDY DESIGN: Retrospective analysis of the AudGen Database. SETTING: Tertiary academic referral center. PATIENTS: Pediatric patients in AudGenDB with a diagnosis EDS. INTERVENTIONS: Appropriate audiologic, otologic, and demographic data were recorded. MAIN OUTCOME MEASURE: One hundred forty one patients met inclusion criteria. Data for each patient were selected based on their first encounter by age with available audiometric data or their first encounter with a type of hearing loss documented. The patients were then stratified by type and severity of hearing loss, and available otologic issues were documented. RESULTS: One hundred nine patients had normal hearing. Thirty two patients had hearing loss, with 19 bilateral, and 13 unilateral. Of the 51 individual ears, 25 had conductive, 23 had sensorineural, and 3 had mixed hearing loss. Audiometric configuration was primarily flat in nature. The hearing loss severity was significantly correlated with age, but not influenced by the type of loss. CONCLUSION: Hearing loss is prevalent in patients with EDS. The hearing loss is equally of conductive and sensorineural origin, with a predisposition to be bilateral. Further evaluation of the underlying pathology of hearing loss in these patients is warranted to aid otolaryngologists and audiologists in diagnosis and management. PMID- 27253075 TI - Ossiculoplasty on Isolated Malleus Fractures: A Human Temporal Bone Study Using Laser Doppler Vibrometry. AB - HYPOTHESIS: In the literature several surgical methods have been reported that aim to improve hearing in patients with isolated malleus fractures; however, it is still not clear which method gives the best results. BACKGROUND: In this study, laser Doppler vibrometry (LDV) was used to compare the outcome of different surgical methods on malleus fractures in fresh frozen human temporal bones. METHODS: Fractured malleus shafts of defrosted human temporal bones were repaired with bone cement, with a malleus prosthesis from cortical bone, or with a partial ossicular replacement prosthesis (PORP) from cortical bone, and LDV measurements were obtained for analysis. RESULTS: The best result was achieved with the bone cement only, applied directly at the site of the fracture. The malleus prosthesis and the PORP gave similar results. CONCLUSION: All three surgical methods gave good results, but when the distal end of the fractured malleus can be attached close to the proximal end, the technique using only cement tends to be the best option. If the parts are too far apart, a malleus prosthesis or a PORP would be good options. PMID- 27253077 TI - Journals and CPD. AB - One of the significant tools for supporting continuing professional development (CPD) is the Institute of Medical Illustrators (IMI) owned publication the Journal of Visual Communication in Medicine. Other journals, for example the Journal of Biological Photography, The British Journal of Photography, British Medical Journal and specialist journals associated with specific areas of medicine, education and illustration, are also helpful. The aim of this paper is to look at journals and CPD together with activities to help you engage with current literature, practice and research. If you look at the examples of CPD activities suggested by both IMI and the Health Professions Council (HPC) one of the recurring themes is the role of journals ( Table 1 ). Journals, alongside conferences, regional and national meetings, are key means of dissemination of research and support for professional development. [Table: see text]. PMID- 27253076 TI - FleQ, a Transcriptional Activator, Is Required for Biofilm Formation In Vitro But Does Not Alter Virulence in a Cholesteatomas Model. AB - HYPOTHESIS: Bacterial biofilm formation within cholesteatomas is responsible for increased persistence and tissue destruction and Pseudomonas aeruginosa deficient in biofilm formation (PAO1 DeltafleQ) are less virulent than the parent bacteria. BACKGROUND: Infected aural cholesteatomas have been demonstrated to be more destructive than uninfected cholesteatomas and infections are more persistent. The chronicity and persistence of infections within cholesteatomas may be because of the presence of biofilm formation. METHODS: Twenty-seven mutant strains of PAO1 were screened for surface adherence. These strains were also screened for static biofilm formation. The biofilms were quantified by staining with crystal violet. Aural cholesteatomas were then induced in Mongolian gerbils by ligation of the ear canal. At the time of ligation, the ear canals were inoculated with wild-type PAO1 and a biofilm deficient PAO1 DeltafleQ strain of P. aeruginosa. A 7 weeks course of ciprofloxacin (20 mg/kg/day) was started on postoperative day 7. Eight weeks after induction of cholesteatomas, the cholesteatoma size, levels of bone destruction, and levels of bone remodeling were evaluated using microCT imaging. RESULTS: PAO1 DeltafleQ was identified as a poorly adherent and deficient biofilm forming mutant strain of P. aeruginosa. Infected cholesteatomas had more growth, bone destruction and bone remodeling than uninfected cholesteatomas. However, there was no difference observed between cholesteatomas infected with PAO1 (biofilm competent strain) and PAO1 DeltafleQ (biofilm deficient strain). CONCLUSION: We demonstrate that the biofilm phenotype is not an important virulence factor in cholesteatomas infected with P. aeruginosa. PMID- 27253078 TI - Narratives in Two Languages: Storytelling of Bilingual Cantonese-English Preschoolers. AB - PURPOSE: The aim of this study was to compare narratives generated by 4-year-old and 5-year-old children who were bilingual in English and Cantonese. METHOD: The sample included 47 children (23 who were 4 years old and 24 who were 5 years old) living in Toronto, Ontario, Canada, who spoke both Cantonese and English. The participants spoke and heard predominantly Cantonese in the home. Participants generated a story in English and Cantonese by using a wordless picture book; language order was counterbalanced. Data were transcribed and coded for story grammar, morphosyntactic quality, mean length of utterance in words, and the number of different words. RESULTS: Repeated measures analysis of variance revealed higher story grammar scores in English than in Cantonese, but no other significant main effects of language were observed. Analyses also revealed that older children had higher story grammar, mean length of utterance in words, and morphosyntactic quality scores than younger children in both languages. Hierarchical regressions indicated that Cantonese story grammar predicted English story grammar and Cantonese microstructure predicted English microstructure. However, no correlation was observed between Cantonese and English morphosyntactic quality. CONCLUSIONS: The results of this study have implications for speech-language pathologists who collect narratives in Cantonese and English from bilingual preschoolers. The results suggest that there is a possible transfer in narrative abilities between the two languages. PMID- 27253080 TI - Rational synthesis of carbon-coated hollow Ge nanocrystals with enhanced lithium storage properties. AB - High-capacity anode materials based on alloy-type group IV elements always have large volume expansion during lithiation when they are used in lithium-ion batteries. Designing hollow structures is a well-established strategy to accommodate the volume change because of sufficient internal void space. Here we report a facile template-free route to prepare hollow Ge nanospheres without using any templates through a quasi-microemulsion method. Ge nanocrystals are preferably self-assembled along the interface of liquid vesicles between water and tetrahydrofuran, and well-defined hollow architectures of ~50 nm in diameter are formed. Both the wall thickness and hollow interiors can be easily tuned. After subsequent carbon coating via pyrolysis of acetylene, the as-formed Ge@C nanocomposite with hollow interiors exhibits a highly reversible capacity of about 920 mA h g(-1) at 200 mA g(-1) over 50 cycles, and excellent rate capability. The small size and the high structural integrity of hollow Ge@C structures contribute to the superior lithium-storage performances. PMID- 27253081 TI - Privacy Practices of Health Social Networking Sites: Implications for Privacy and Data Security in Online Cancer Communities. AB - While online communities for social support continue to grow, little is known about the state of privacy practices of health social networking sites. This article reports on a structured content analysis of privacy policies and disclosure practices for 25 online ovarian cancer communities. All of the health social networking sites in the study sample provided privacy statements to users, yet privacy practices varied considerably across the sites. The majority of sites informed users that personal information was collected about participants and shared with third parties (96%, n = 24). Furthermore, more than half of the sites (56%, n = 14) stated that cookies technology was used to track user behaviors. Despite these disclosures, only 36% (n = 9) offered opt-out choices for sharing data with third parties. In addition, very few of the sites (28%, n = 7) allowed individuals to delete their personal information. Discussions about specific security measures used to protect personal information were largely missing. Implications for privacy, confidentiality, consumer choice, and data safety in online environments are discussed. Overall, nurses and other health professionals can utilize these findings to encourage individuals seeking online support and participating in social networking sites to build awareness of privacy risks to better protect their personal health information in the digital age. PMID- 27253082 TI - Acetate Salts as Nonhalogen Additives To Improve Perovskite Film Morphology for High-Efficiency Solar Cells. AB - A two-step method has been popularly adopted to fabricate a perovskite film of planar heterojunction organo-lead halide perovskite solar cells (PSCs). However, this method often generates uncontrollable film morphology with poor coverage. Herein, we report a facile method to improve perovskite film morphology by incorporating a small amount of acetate (CH3COO(-), Ac(-)) salts (NH4Ac, NaAc) as nonhalogen additives in CH3NH3I solution used for immersing PbI2 film, resulting in improved CH3NH3PbI3 film morphology. Under the optimized NH4Ac additive concentration of 10 wt %, the best power conversion efficiency (PCE) reaches 17.02%, which is enhanced by ~23.2% relative to that of the pristine device without additive, whereas the NaAc additive does not lead to an efficiency enhancement despite the improvement of the CH3NH3PbI3 film morphology. SEM study reveals that NH4Ac and NaAc additives can both effectively improve perovskite film morphology by increasing the surface coverage via diminishing pinholes. The improvement on CH3NH3PbI3 film morphology is beneficial for increasing the optical absorption of perovskite film and improving the interfacial contact at the perovskite/spiro-OMeTAD interface, leading to the increase of short-circuit current and consequently efficiency enhancement of the PSC device for NH4Ac additive only. PMID- 27253079 TI - Ion channel regulation by beta-secretase BACE1 - enzymatic and non-enzymatic effects beyond Alzheimer's disease. AB - beta-site APP-cleaving enzyme 1 (BACE1) has become infamous for its pivotal role in the pathogenesis of Alzheimer's disease (AD). Consequently, BACE1 represents a prime target in drug development. Despite its detrimental involvement in AD, it should be quite obvious that BACE1 is not primarily present in the brain to drive mental decline. In fact, additional functions have been identified. In this review, we focus on the regulation of ion channels, specifically voltage-gated sodium and KCNQ potassium channels, by BACE1. These studies provide evidence for a highly unexpected feature in the functional repertoire of BACE1. Although capable of cleaving accessory channel subunits, BACE1 exerts many of its physiologically significant effects through direct, non-enzymatic interactions with main channel subunits. We discuss how the underlying mechanisms can be conceived and develop scenarios how the regulation of ion conductances by BACE1 might shape electric activity in the intact and diseased brain and heart. PMID- 27253083 TI - Light Field Imaging Based Accurate Image Specular Highlight Removal. AB - Specular reflection removal is indispensable to many computer vision tasks. However, most existing methods fail or degrade in complex real scenarios for their individual drawbacks. Benefiting from the light field imaging technology, this paper proposes a novel and accurate approach to remove specularity and improve image quality. We first capture images with specularity by the light field camera (Lytro ILLUM). After accurately estimating the image depth, a simple and concise threshold strategy is adopted to cluster the specular pixels into "unsaturated" and "saturated" category. Finally, a color variance analysis of multiple views and a local color refinement are individually conducted on the two categories to recover diffuse color information. Experimental evaluation by comparison with existed methods based on our light field dataset together with Stanford light field archive verifies the effectiveness of our proposed algorithm. PMID- 27253084 TI - Operative Management of Adult Spinal Deformity Results in Significant Increases in QALYs Gained Compared to Nonoperative Management: Analysis of 479 Patients With Minimum 2-Year Follow-Up. AB - STUDY DESIGN: Retrospective review of prospective multicenter adult spinal deformity (ASD) database. OBJECTIVE: To compare the quality-adjusted life years (QALYs) between operative and nonoperative treatments for ASD patients. SUMMARY OF BACKGROUND DATA: Operative management of ASD repeatedly demonstrates improvements in HRQOL over nonoperative treatment. However, little is reported regarding QALY improvements after surgical correction of ASD. METHODS: Inclusion criteria: >=18 years, ASD. Health utility values were calculated from SF6D scores and used to calculate QALYs at minimum 2 years from the baseline utility value as well as at 1, 2, and 3 years for the available patients. A 1:1 propensity score matching using six baseline variables was conducted to account for the nonrandom distribution of operative and nonoperative treatments. RESULTS: Four hundred seventy-nine patients were included (OP:258, 70.7%, NONOP:221, 47.1%). One hundred fifty-one (OP:90, NONOP:61) had complete 1, 2, and 3 year data available for QALY trending. Unmatched results are not listed in the abstract. Mean baseline utility scores were statistically similar between the matched groups (OP: 0.609 +/- 0.093, NONOP: 0.600 +/- 0.091, P = 0.6401) and at 2 year min postop mean OP QALY was greater than NONOP (1.377 +/- 0.345 vs. 1.256 +/- 0.286, respectively, P < 0.01). For the subanalysis cohort, mean OP QALYs at 1, 2, and 3 years postoperative were all significantly greater than NONOP, P < 0.03 for all (1 yr: 0.651 +/- 0.089 vs. 0.61 +/- 0.079, 2 yr: 1.29 +/- 0.157 vs. 1.189 +/- 0.141, and 3 yr: 1.903 +/- 0.235 vs. 1.749 +/- 0.198, respectively). Matched OP had a larger QALYs gained (from baseline) at 2 year minimum postoperative (0.112 +/- 0.243 vs. 0.008 +/- 0.195, P < 0.01). For subanalysis of patients with complete 1 to 3 years data, OP had a significantly larger QALYs gained at 1, 2, and 3 years compared with NONOP: 1 year (0.073 +/- 0.121 vs. 0.029 +/- 0.082, P = 0.0447), 2 years (0.167 +/- 0.232 vs. 0.036 +/- 0.173, P = 0.0030), and 3years (0.238 +/- 0.379 vs. 0.059 +/- 0.258, P < 0.01). CONCLUSION: The operative treatment of adult spinal deformity results in significantly greater mean QALYs and QALYs gained at minimum 2 years postop as well as at the 1-, 2-, and 3-year time points compared with nonoperative management. LEVEL OF EVIDENCE: 3. PMID- 27253085 TI - Xenon Combined with Therapeutic Hypothermia Is Not Neuroprotective after Severe Hypoxia-Ischemia in Neonatal Rats. AB - BACKGROUND: Therapeutic hypothermia (TH) is standard treatment following perinatal asphyxia in newborn infants. Experimentally, TH is neuroprotective after moderate hypoxia-ischemia (HI) in seven-day-old (P7) rats. However, TH is not neuroprotective after severe HI. After a moderate HI insult in newborn brain injury models, the anesthetic gas xenon (Xe) doubles TH neuroprotection. The aim of this study was to examine whether combining Xe and TH is neuroprotective as applied in a P7 rat model of severe HI. DESIGN/METHODS: 120 P7 rat pups underwent a severe HI insult; unilateral carotid artery ligation followed by hypoxia (8% O2 for 150min at experimental normothermia (NT-37: Trectal 37 degrees C). Surviving pups were randomised to immediate NT-37 for 5h (n = 36), immediate TH-32: Trectal 32 degrees C for 5h (n = 25) or immediate TH-32 plus 50% inhaled Xe for 5h (n = 24). Pups were sacrificed after one week of survival. Relative area loss of the ligated hemisphere was measured, and neurons in the subventricular zone of this injured hemisphere were counted, to quantify brain damage. RESULTS: Following the HI insult, median (interquartile range, IQR) hemispheric brain area loss was similar in all groups: 63.5% (55.5-75.0) for NT-37 group, 65.0% (57.0-65.0) for TH-32 group, and 66.5% (59.0-72.0) for TH-32+Xe50% group (not significant). Correspondingly, there was no difference in neuronal cell count (NeuN marker) in the subventricular zone across the three treatment groups. CONCLUSIONS: Immediate therapeutic hypothermia with or without additional 50% inhaled Xe, does not provide neuroprotection one week after severe HI brain injury in the P7 neonatal rat. This model aims to mimic the clinical situation in severely asphyxiated neonates and treatment these newborns remains an ongoing challenge. PMID- 27253086 TI - Cigarette Smoke Extract-Exposed Methicillin-Resistant Staphylococcus aureus Regulates Leukocyte Function for Pulmonary Persistence. AB - Cigarette smoke (CS) predisposes exposed individuals to respiratory infections not only by suppressing immune response but also by enhancing the virulence of pathogenic bacteria. As per our observations, in methicillin-resistant Staphylococcus aureus strain USA300, CS extract (CSE) potentiates biofilm formation via the down-regulation of quorum-sensing regulon accessory gene regulator. Because accessory gene regulator is a global regulator of the staphylococcal virulome, in the present study we sought to identify the effects of CS exposure on staphylococcal gene expression using RNAseq. Comparative analysis of RNAseq profiles revealed the up-regulation of important virulence genes encoding surface adhesins (fibronectin- and fibrinogen-binding proteins A and B and clumping factor B) and proteins involved in immune evasion, such as staphylocoagulase, staphylococcal protein A, and nuclease. In concurrence with the RNAseq data, we observed: (1) significant up-regulation of the ability of CSE exposed USA300 to evade phagocytosis by macrophages and neutrophils, a known function of staphylococcal protein A; and (2) twofold higher (P < 0.001) number of CSE-exposed USA300 escaping neutrophil extracellular trap-mediated killing by neutrophils as a result of CS-mediated induction of nuclease. Importantly, in three different mouse strains, C57BL6/J, Balb/C, and A/J, we observed significantly higher pulmonary bacterial burden in animals infected with CSE exposed USA300 as compared with medium-exposed control USA300. Taken together, these observations indicate that bioactive chemicals in CS induce hypervirulence by augmenting the ability of USA300 to evade bactericidal functions of leukocytes, such as phagocytosis and neutrophil extracellular trap-mediated killing. PMID- 27253087 TI - Prophylaxis in von Willebrand Disease: Coming of Age? AB - Although in most cases von Willebrand disease (VWD) is a mild disorder, a subgroup of patients experience frequent bleeding. In contrast to severe hemophilia in which prophylaxis is the accepted standard of care, this is less frequently used in VWD. Most type 1 VWD patients can be adequately managed with episodic desmopressin and tranexamic acid. In patients with more severe disease, especially those with type 3 VWD, joint bleeds, epistaxis, menorrhagia, and gastrointestinal bleeding are problematic and usually require treatment with von Willebrand factor/factor VIII (VWF/FVIII) concentrate. While in the past these patients were managed with on-demand VWF/FVIII concentrate, several recent reports have demonstrated the value of prophylactic treatment. Despite some uncertainties about the economic impact of treatment of severe VWD, prophylaxis with VWF concentrate should now be considered as the standard of care for the more severe end of the spectrum of affected individuals. The recent introduction of recombinant VWF concentrate is likely to improve the acceptability of prophylaxis in VWD. PMID- 27253088 TI - Severe Thrombotic Complications in Congenital Afibrinogenemia: A Pathophysiological and Management Dilemma. AB - Congenital afibrinogenemia (CA) is a disease characterized by a complex pathophysiology, involving both the procoagulant and fibrinolytic systems, as well as platelet activity. Although hemorrhagic diathesis represents the most frequent clinical presentation of this disorder, severe thrombotic events can occur. It is not yet clear if these events are strictly related to the disease itself or to the fibrinogen replacement therapy. Different hypotheses on the pathophysiological mechanisms have been proposed. It is well known that fibrinogen/fibrin has a role in the downregulation of thrombin generation in plasma. In the absence of circulating fibrinogen, this "antithrombin" activity is missing and plasma thrombin levels rise; this excess of thrombin could promote clotting of the infused fibrinogen, initiating the thrombotic process. Furthermore, the observation of impaired plasmin generation in the plasma of CA patients has raised the hypothesis of a fibrinolytic system deficiency. We report the case of a CA male patient who at the age of 36 years experienced an arterial thrombosis in his left lower limb. Despite an aggressive medical treatment with low-molecular-weight heparin, fibrinolytic and antiplatelet agents, the arterial thrombosis progressed to the obstruction of the whole left arterial district and the patient underwent the amputation of the left lower limb. This case demonstrates the complexity of pathophysiology and clinical management of a "so called" bleeding disorder as CA. PMID- 27253089 TI - The electrostatic co-assembly in non-stoichiometric aqueous mixtures of copolymers composed of one neutral water-soluble and one polyelectrolyte (either positively or negatively charged) block: a dissipative particle dynamics study. AB - The electrostatic co-assembly in non-stoichiometric aqueous mixtures of diblock copolymers composed of a neutral water-soluble block and an either positively or negatively charged polyelectrolyte (PE) block has been studied by dissipative particle dynamics (DPD) simulations. The employed DPD variant includes explicit electrostatics and enables the investigation of the role of small ions in the co assembly. The properties of core-shell associates containing insoluble interpolyelectrolyte complex cores and protective neutral shells were investigated as functions of the ratio of positive-to-negative charges in the system. This ratio was varied by increasing the number of positively charged PE chains of the same length as those of negatively charged chains, and by changing the PE length and charge density. The simulation results show that the associates formed in non-stoichiometric mixtures differ from those formed in stoichiometric mixtures: their association numbers are lower, their cores are charged and a fraction of excess chains remain free in the non-associated state. The study demonstrates the important role of the compatibility of the counterions with the polymer blocks. It simultaneously emphasizes the necessity of including the electrostatic interaction of all the charged species in the DPD computational scheme. PMID- 27253136 TI - Trypanosoma cruzi: Time for International Recognition as a Foodborne Parasite. PMID- 27253137 TI - Sensitive and Quantitative Detection of C-Reaction Protein Based on Immunofluorescent Nanospheres Coupled with Lateral Flow Test Strip. AB - Sensitive and quantitative detection of protein biomarkers with a point-of-care (POC) assay is significant for early diagnosis, treatment, and prognosis of diseases. In this paper, a quantitative lateral flow assay with high sensitivity for protein biomarkers was established by utilizing fluorescent nanospheres (FNs) as reporters. Each fluorescent nanosphere (FN) contains 332 +/- 8 CdSe/ZnS quantum dots (QDs), leading to its superstrong luminescence, 380-fold higher than that of one QD. Then a detection limit of 27.8 pM C-reaction protein (CRP) could be achieved with an immunofluorescent nanosphere (IFN)-based lateral flow test strip. The assay was 257-fold more sensitive than that with a conventional Au based lateral flow test strip for CRP detection. Besides, the fluorescence intensity of FNs and bioactivity of IFNs were stable during 6 months of storage. Hence, the assay owns good reproducibility (intra-assay variability of 5.3% and interassay variability of 6.6%). Furthermore, other cancer biomarkers (PSA, CEA, AFP) showed negative results by this method, validating the excellent specificity of the method. Then the assay was successfully applied to quantitatively detect CRP in peripheral blood plasma samples from lung cancer and breast cancer patients, and healthy people, facilitating the diagnosis of lung cancer. It holds a good prospect of POC protein biomarker detection. PMID- 27253138 TI - Engineering Gram Selectivity of Mixed-Charge Gold Nanoparticles by Tuning the Balance of Surface Charges. AB - Nanoparticles covered with ligand shells comprising both positively and negatively charged ligands exhibit Gram-selective antibacterial action controlled by a single experimental parameter, namely the proportion of [+] and [-] ligands tethered onto these particles. Gram selectivity is attributed to the interplay between polyvalent electrostatic and non-covalent interactions that work in unison to disrupt the bacterial cell wall. The [+/-] nanoparticles are effective in low doses, are non-toxic to mammalian cells, and are tolerated well in mice. These results constitute the first example of rational engineering of Gram selectivity at the (macro)molecular level. PMID- 27253139 TI - Self-perceived need for dental treatment and related factors. A cross-sectional population-based study. AB - This study compared adolescents' self-perceived need for orthodontic treatment with the normative need for such treatment and investigated associations between socioeconomic and demographic variables and self-perceptions of dental malocclusion. This cross-sectional study involved 1015 schoolchildren aged 12-15 years in Sao Luis, Maranhao, Brazil. The following data were collected using a questionnaire and an orthodontic examination card: demographic and identifying data, socioeconomic data, educational levels of family, household income, economic classification criteria, and self-reported skin color behavioral data, and oral health data. Normative occlusal condition was examined using the Angle classification and Dental Aesthetic Index (DAI). Data were analyzed using the chi squared test (to analyze differences in the frequency distribuition of qualitative variables) and Poisson regression (to stimate associations between the perceived need of orthodontic treatment and study covariates), with a 5% significance level. Schoolchildren's self-perceived need for orthodontic treatment was associated with sex (p = 0.022) and the normative need for treatment (p = 0.004). Among socioeconomic, demographic, and oral health variables, only sex [prevalence ratio (PR) = 1.15; 95% confidence interval (95%CI) = 1.04-1.28; p = 0.009] and the normative need for orthodontic treatment (PR = 1.19; 95%CI = 1.08-1.32; p < 0.001) were associated with the perception of malocclusion, with female adolescents reporting a greater need for orthodontic treatment. Female adolescents seems to be more sensitive to oral health problems. The results suggest that the DAI score might reflect a self-perceived need for orthodontic treatment and the Angle classification might overestimate the orthodontic treatment need. PMID- 27253140 TI - Low-intensity laser phototherapy enhances the proliferation of dental pulp stem cells under nutritional deficiency. AB - Dental trauma in immature permanent teeth can damage pulp vascularization, which leads to necrosis and cessation of apexogenesis. Studies on tissue engineering using stem cells from human exfoliated deciduous teeth (SHEDs) have yielded promising results. Laser phototherapy (LPT) is able to influence the proliferation and differentiation of these cells, which could improve tissue engineering. SHEDs (eighth passage) were seeded into 96-well culture plates (103 cells/well) and were grown in culture medium supplemented with 15% defined fetal bovine serum (FBS) for 12 h. After determining the appropriate nutrition deficiency status (5% FBS), the cells were assigned into four groups: 1) G1 - 15% FBS (positive control); 2) G2 - 5% FBS (negative control); 3) G3 - 5% FBS+LPT 3 J/cm2; and 4) G4 - 5% FBS+LPT 5 J/cm2. For the LPT groups, two laser irradiations at 6 h intervals were performed using a continuous wave InGaAlP diode laser (660 nm, with a spot size of 0.028 cm2, 10 mW) in punctual and contact mode. Cell viability was assessed via an MTT reduction assay immediately after the second laser irradiation (0 h) and 24, 48, and 72 h later. We found that G3 and G4 presented a significantly higher cell growth rate when compared with G2 (p < 0.01). Moreover, G4 exhibited a similar cell growth rate as G1 throughout the entire experiment (p > 0.05). These findings indicate that LPT with 5 J/cm2 can enhance the growth of SHEDs during situations of nutritional deficiency. Therefore, LPT could be a valuable adjunct treatment in tissue engineering when using stem cells derived from the dental pulp of primary teeth. PMID- 27253141 TI - Prosthetic abutment influences bone biomechanical behavior of immediately loaded implants. AB - This study aimed to evaluate the influence of the type of prosthetic abutment associated to different implant connection on bone biomechanical behavior of immediately and delayed loaded implants. Computed tomography-based finite element models comprising a mandible with a single molar implant were created with different types of prosthetic abutment (UCLA or conical), implant connection (external hexagon, EH or internal hexagon, IH), and occlusal loading (axial or oblique), for both immediately and delayed loaded implants. Analysis of variance at 95%CI was used to evaluate the peak maximum principal stress and strain in bone after applying a 100 N occlusal load. The results showed that the type of prosthetic abutment influences bone stress/strain in only immediately loaded implants. Attachment of conical abutments to IH implants exhibited the best biomechanical behavior, with optimal distribution and dissipation of the load in peri-implant bone. PMID- 27253142 TI - Validation of cone-beam computed tomography as a predictor of osteoporosis using the Klemetti classification. AB - This study aimed at evaluating the validity of cone-beam computed tomography (CBCT) for assessing mandibular bone quality using the Klemetti classification. The morphology of the endosteal mandibular cortex of 30 (60 hemi-mandibles) postmenopausal women between the ages of 45 and 80 years was evaluated based on the Klemetti classification in panoramic radiographs used as reference images. Afterwards, panoramic reconstruction and cross-sectional slices of CBCT examinations of these patients were analyzed and categorized according to the same classification. All the images were assessed by two oral radiologists. The McNemar-Bowker test compared the agreement between the CBCT images and the reference images. No differences were found between the diagnostic results based on panoramic radiography and panoramic reconstruction. However, the mean scores for the cross-sectional evaluation were higher, and the results, statistically different from the others. Based on the disagreement found between the panoramic radiographs and the CBCT cross-sectional slices, the Klemetti classification is not an adequate means of assessing bone quality with CBCT. On the other hand, the higher values found for the cross-sectional slices could be associated with better visibility on the CBCT images. PMID- 27253143 TI - Maternal care influence on children's caries prevalence in southern Brazil. AB - This study aimed to investigate the influence of specific maternal-factors on caries prevalence in offspring. This cross sectional study was conducted in Pelotas, Brazil nested in a cohort of adolescent mothers with children aged 24-42 months. A questionnaire was administered to collect information in relationship to socio-economic, demographic, and behavioral maternal variables. The outcome (children's dental caries prevalence - dmfs > 0) was collected from clinical examinations. Bivariate and multivariate analyses were conducted. A total of 538 mother/child dyads were evaluated and 15.1% of the children exhibited caries. Adjusted multivariate analysis showed children from mothers living without partners (p < 0.027) had more caries than those living with partners. Maternal perception of a child's oral health was associated to occurrence of caries, particularly when mothers classified their child as poor and these children had a higher level of caries. In addition, mothers accurately evaluated their child's teeth when associated with caries occurrence. Maternal oral health care practices were associated with children's caries prevalence. Our results demonstrated mothers accurately evaluated the oral health of their offspring. PMID- 27253144 TI - Effect of new innovative restorative carbomised glass cement on intrapulpal temperature rise: an ex-vivo study. AB - This study aimed to evaluate the temperature changes that occurred in the pulp chamber when using GCP Glass Carbomer Fill (GCP) and two different resin-modified glass-ionomer (RGI) restorative materials at different dentin thicknesses. A standardized Class I occlusal cavity with 1 mm or 2 mm dentin thickness was prepared in the extracted human molar teeth. RGI and GCP fills were placed in the cavities and cured with two different light-curing units. This study included a total of 120 samples, with 20 samples in each group. The pulp microcirculation method was used for measuring the intrapulpal temperature changes. Statistical analysis was performed using the two-way ANOVA and Tukey HSD multiple comparison tests. Statistically significant differences were observed between 1 mm and 2 mm dentin thicknesses (p < 0.001). The GCP groups (both 1 mm and 2 mm dentin thicknesses) exhibited higher temperatures than the other groups (p < 0.001), and Fuji II LC and Photac Fil Quick Aplicap showed similar values (p > 0.05). The highest temperature changes were observed with 1 mm dentin thickness. While RGI materials in both dentin thicknesses did not cause temperature changes that were harmful to the pulp, GCP CarboLED LCU caused the highest intrapulpal temperature rise, and these values were borderline harmful to the dental pulp. PMID- 27253145 TI - Thickness and nanomechanical properties of protective layer formed by TiF4 varnish on enamel after erosion. AB - The layer formed by fluoride compounds on tooth surface is important to protect the underlying enamel from erosion. However, there is no investigation into the properties of protective layer formed by NaF and TiF4 varnishes on eroded enamel. This study aimed to evaluate the thickness, topography, nanohardness, and elastic modulus of the protective layer formed by NaF and TiF4 varnishes on enamel after erosion using nanoindentation and atomic force microscopy (AFM). Human enamel specimens were sorted into control, NaF, and TiF4 varnish groups (n = 10). The initial nanohardness and elastic modulus values were obtained and varnishes were applied to the enamel and submitted to erosive challenge (10 cycles: 5 s cola drink/5 s artificial saliva). Thereafter, nanohardness and elastic modulus were measured. Both topography and thickness were evaluated by AFM. The data were subjected to ANOVA, Tukey's test and Student's t test (alpha = 0.05). After erosion, TiF4 showed a thicker protective layer compared to the NaF group and nanohardness and elastic modulus values were significantly lower than those of the control group. It was not possible to measure nanohardness and elastic modulus in the NaF group due to the thin protective layer formed. AFM showed globular deposits, which completely covered the eroded surface in the TiF4 group. After erosive challenge, the protective layer formed by TiF4 varnish showed significant properties and it was thicker than the layer formed by NaF varnish. PMID- 27253146 TI - Clinical outcome of root caries restorations using ART and rotary techniques in institutionalized elders. AB - The aim of this study was to compare the clinical performance of root caries restorations after a six-month period using two methods, a conventional technique with rotary instruments and an atraumatic restorative technique (ART), in an institutionalized elderly population in the city of Bogota, Colombia. Root caries represents a multifactorial, progressive, chronic lesion with softened, irregular and darkened tissue involving the radicular surface; it is highly prevalent in the elderly, especially in those who are physically or cognitively impaired. A quasi-experimental, double-blind, longitudinal study was carried out after cluster randomization of the sample. Two different experienced dentists, previously trained, performed the restorations using each technique. After six months, two new investigators performed a blind evaluation of the condition of the restorations. The results showed a significantly higher rate of success (92.9%) using the conventional technique (p < 0.03). However, we concluded that ART may have been the preferred technique in the study population because 81% of those restorations survived or were successful during the observation period. PMID- 27253147 TI - Mineral metabolism: progress in the face of complexity. PMID- 27253149 TI - Glucose time series complexity as a predictor of type 2 diabetes. AB - BACKGROUND: Complexity analysis of glucose profile may provide valuable information about the gluco-regulatory system. We hypothesized that a complexity metric (detrended fluctuation analysis, DFA) may have a prognostic value for the development of type 2 diabetes in patients at risk. METHODS: A total of 206 patients with any of the following risk factors (1) essential hypertension, (2) obesity or (3) a first-degree relative with a diagnosis of diabetes were included in a survival analysis study for a diagnosis of new onset type 2 diabetes. At inclusion, a glucometry by means of a Continuous Glucose Monitoring System was performed, and DFA was calculated for a 24-h glucose time series. Patients were then followed up every 6 months, controlling for the development of diabetes. RESULTS: In a median follow-up of 18 months, there were 18 new cases of diabetes (58.5 cases/1000 patient-years). DFA was a significant predictor for the development of diabetes, with ten events in the highest quartile versus one in the lowest (log-rank test chi2 = 9, df = 1, p = 0.003), even after adjusting for other relevant clinical and biochemical variables. In a Cox model, the risk of diabetes development increased 2.8 times for every 0.1 DFA units. In a multivariate analysis, only fasting glucose, HbA1c and DFA emerged as significant factors. CONCLUSIONS: Detrended fluctuation analysis significantly performed as a harbinger of type 2 diabetes development in a high-risk population. Complexity analysis may help in targeting patients who could be candidates for intensified treatment. Copyright (c) 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd. PMID- 27253150 TI - Superconductivity and Charge Density Wave in ZrTe3-xSex. AB - Charge density wave (CDW), the periodic modulation of the electronic charge density, will open a gap on the Fermi surface that commonly leads to decreased or vanishing conductivity. On the other hand superconductivity, a commonly believed competing order, features a Fermi surface gap that results in infinite conductivity. Here we report that superconductivity emerges upon Se doping in CDW conductor ZrTe3 when the long range CDW order is gradually suppressed. Superconducting critical temperature Tc(x) in ZrTe3-xSex (0 <= x <= 0.1) increases up to 4 K plateau for 0.04 <= x <= 0.07. Further increase in Se content results in diminishing Tc and filametary superconductivity. The CDW modes from Raman spectra are observed in x = 0.04 and 0.1 crystals, where signature of ZrTe3 CDW order in resistivity vanishes. The electronic-scattering for high Tc crystals is dominated by local CDW fluctuations at high temperatures, the resistivity is linear up to highest measured T = 300 K and contributes to substantial in-plane anisotropy. PMID- 27253151 TI - (+) RNA virus replication compartments: a safe home for (most) viral replication. AB - This review describes recent advances in our understanding of the mechanisms by which (+) RNA viruses establish their replication niche. PMID- 27253152 TI - Helical tomotherapy for bilateral breast cancer: Clinical experience. AB - We report our initial clinical experience with using Helical tomotherapy to irradiate the bilateral breasts/chest-wall and regional nodes. METHODS: The records of patients who received bilateral irradiation of the breast/chest-wall and regional nodes with tomotherapy were retrospectively reviewed. Clinical outcomes for tumor and normal tissues were assessed. RESULTS: From August 2011 to January 2016, nine women were identified; median age 52 years (range 37-74), mean follow up was 10.3 months (range 0.3-34). In two patients, tomotherapy represented re-irradiation to one side. All received regional nodal irradiation. The average lung V20 was 29% (range 25-35), average lung V5 was 66% (range 51 75). Average heart mean dose was 20 Gy (range 13-28). NORMAL TISSUE OUTCOMES: Acute toxicity during radiation included dysphagia (5/9), fatigue (4/9), nausea and weight loss (1/9) and skin desquamation (9/9). Two patients were lost to long follow-up and one patient recently completed treatment. Longer-term toxicity included: pneumonitis (1/6), elevated liver function tests (1/6) and sternal osteonecrosis (1/6; in patient with prior sternal surgery). CONCLUSIONS: Despite the small numbers of patients and relatively short follow-up, significant clinical toxicities were observed. Given the rarity of this situation and relatively high rate of complications in this small series, considerable care should be taken in minimizing dose to normal structures. Longer follow up with larger numbers of patients will be needed to establish safe dosimetric parameters for bilateral breasts/chest wall and nodal irradiation with tomotherapy. PMID- 27253153 TI - Breast cancer-associated venous thromboembolism: A case-control study. AB - Breast cancer is frequently associated with venous thromboembolism (VTE). VTE may result in significant morbidity, a substantial economic burden and even leads to patients' death. Risk factor identification and management of VTE in breast cancer patients remains poorly studied. We evaluated breast cancer patients' baseline and treatment characteristics in predicting VTE occurrence as well as its prognosis. We conducted a case-control study of all breast cancer patients with a VTE diagnosed between January 2007 and December 2011 at the Instituto Nacional de Cancer (INCA) in Brazil. Two hundred and twenty five patients developed VTE and were compared with 225 controls, in the 5-year study period. The bulk of the thrombotic events were unilateral (94.2%) VTEs of the lower extremity (78.7%), largely proximally located (78%). VTE occurred more often within the first 3 years after the diagnosis of cancer (66.2%), being more common in the first 6 months (21.8%). Significant predictors of developing VTE were age 50 years and over (OR 1.85, 95% CI: 1.16-2.95), PS equal to or above 3 (OR 2.01, 95% CI: 1.24-3.26), and the presence of a CVC (OR 2.56, 95% CI: 1.42-4.62). This large retrospective analysis of VTE in breast cancer patients confirms that most events occur early in the treatment course. The incidence of VTE was associated with patients' age, PS, and the presence of CVC. Prospective studies are needed to evaluate outpatient thromboprophylaxis for selected groups of patients. PMID- 27253154 TI - Microfluidic nanoprecipitation systems for preparing pure drug or polymeric drug loaded nanoparticles: an overview. AB - INTRODUCTION: This review gives an overview of the different microfluidic setups used to produce either pure drug or drug-loaded polymeric nanoparticles. AREA COVERED: We propose a description of the different fluidic principles reported in the literature, explaining their respective design and configuration in parallel with the technical challenges related to the nanoprecipitation of the polymer, in relation with the results obtained, e.g., particle size, distribution and productivity. EXPERT OPINION: This review is mostly intended for a broad readership and provides key tools regarding the choice of microfluidic setups, tailored to given specifications. We discuss the specificities and geometries of the microfluidic devices intended to nanoprecipitation, advantages, drawbacks and limitations. PMID- 27253155 TI - Alcohol attitudes, motives, norms, and personality traits longitudinally classify nondrinkers, moderate drinkers, and binge drinkers using discriminant function analysis. AB - INTRODUCTION: Binge drinking is commonly defined in the literature as consuming at least 5 drinks for males and 4 drinks for females. These quantities correspond to approximately a blood alcohol concentration of 0.08%, the level of intoxication making it illegal to drive in the United States. METHODS: The study scrutinized the longitudinal classification of three drinker types using male (n=155) and female (n=351) college students. Measures of personality (sensation seeking, extraversion, agreeableness, conscientiousness, neuroticism, and openness), alcohol attitudes, alcohol motivations (social, coping, enhancement, and conformity), and alcohol social norms (typical students, friends, closest friends, and parents) were administered at Time 1. Drinker type (nondrinkers, moderate drinkers, or binge drinkers) was assessed one month later. RESULTS: Discriminant function analyses revealed that the set of measures statistically distinguished among the three drinker types. The first function was significant and yielded high loadings for attitudes, social motives, enhancement motives, coping motives, closest friend norms, and friend norms for both genders. Model classification accuracy was 73% for the male and 67% female samples. Multivariate analysis of variance (MANOVA) compared mean differences in a 2 (gender: males or females)*3 (drinker type: nondrinkers, moderate drinkers, or binge drinkers) design. Measures systematically differing across all pairwise comparisons of the three drinker types, starting from the strongest effect (eta-squared), were as follows: alcohol attitudes, social motives, enhancement motives, closest friend norms, friend norms, coping motives, sensation seeking, and extraversion. CONCLUSIONS: Attitude, motivation, and norm variables tended to be more important than personality in distinguishing drinker types. Considering the malleability of attitudes and belief motivations, the risk variables of alcohol attitudes, social motives, and enhancement motives identified in this research warrant consideration in prevention and campaign efforts targeting problematic drinking. PMID- 27253157 TI - Structure and Stability of Carbohydrate-Lipid Interactions. Methylmannose Polysaccharide-Fatty Acid Complexes. AB - We report a detailed study of the structure and stability of carbohydrate-lipid interactions. Complexes of a methylmannose polysaccharide (MMP) derivative and fatty acids (FAs) served as model systems. The dependence of solution affinities and gas-phase dissociation activation energies (Ea ) on FA length indicates a dominant role of carbohydrate-lipid interactions in stabilizing (MMP+FA) complexes. Solution (1) H NMR results reveal weak interactions between MMP methyl groups and FA acyl chain; MD simulations suggest the complexes are disordered. The contribution of FA methylene groups to the Ea is similar to that of heats of transfer of n-alkanes from the gas phase to polar solvents, thus suggesting that MMP binds lipids through dipole-induced dipole interactions. The MD results point to hydrophobic interactions and H-bonds with the FA carboxyl group. Comparison of collision cross sections of deprotonated (MMP+FA) ions with MD structures suggests that the gaseous complexes are disordered. PMID- 27253156 TI - Maternal AP determinants in the Drosophila oocyte and embryo. AB - An animal embryo cannot initiate its journey of forming a new life on its own. It must rely on maternally provided resources and inputs to kick-start its developmental process. In Drosophila, the initial polarities of the embryo along both the anterior-posterior (AP) and dorsal-ventral (DV) axes are also specified by maternal determinants. Over the past several decades, genetic and molecular studies have identified and characterized such determinants, as well as the zygotic genetic regulatory networks that control patterning in the early embryo. Extensive studies of oogenesis have also led to a detailed knowledge of the cellular and molecular interactions that control the formation of a mature egg. Despite these efforts, oogenesis and embryogenesis have been studied largely as separate problems, except for qualitative aspects with regard to maternal regulation of the asymmetric localization of maternal determinants. Can oogenesis and embryogenesis be viewed from a unified perspective at a quantitative level, and can that improve our understanding of how robust embryonic patterning is achieved? Here, we discuss the basic knowledge of the regulatory mechanisms controlling oogenesis and embryonic patterning along the AP axis. We explore properties of the maternal Bicoid gradient in relation to embryo size in search for a unified framework for robust AP patterning. WIREs Dev Biol 2016, 5:562-581. doi: 10.1002/wdev.235 For further resources related to this article, please visit the WIREs website. PMID- 27253170 TI - Relation Between Solvent Quality and Phase Behavior of Ternary Mixtures of Polymers and Two Solvents that Exhibit Cononsolvency. AB - The phase boundaries of polymer solutions in mixed solvents can be extremely complex due to the many competing van der Waals and associative interactions that can arise in these ubiquitous and technologically important complex fluids. The present paper focuses specific attention on ternary solutions of polymers (B) dissolved in a mixture of two solvents (A, C) that competitively associate with the polymer. We are particularly concerned with explaining the origin of the peculiar phenomenon of cononsolvency in mixed solvents, where a mixture of two individually good solvents behaves effectively as a poor solvent. Our computations are based on a recently developed generalization of Flory-Huggins theory that incorporates the competitive solvation of a polymer by two associating solvents. On the basis of this framework, we evaluate the limit of polymer phase stability (spinodal curves) and the second osmotic virial coefficient [Formula: see text] as a function of temperature and the composition of the pure solvent mixture that is maintained in osmotic equilibrium with the ternary solution. The calculations provide new insights into the miscibility patterns of ternary A/B/C polymer solutions exhibiting cononsolvency. PMID- 27253171 TI - Sorafenib in metastatic uveal melanoma: efficacy, toxicity and health-related quality of life in a multicentre phase II study. AB - BACKGROUND: The aim of the study was to analyse efficacy, safety, and health related quality of life (HRQoL) for sorafenib treatment in patients with metastatic uveal melanoma. METHODS: A multicentre, single-arm phase II trial was conducted. The primary objective was to determine the non-progression rate (RECIST) at 24 weeks for patients receiving sorafenib at a dose of 800 mg per day. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and HRQoL. RESULTS: Thirty-two patients were included. Ten patients showed non-progression at 24 weeks (31.2%) without objective tumour responses. The estimated 24-week PFS was 31.2% (95% CI: 14.8%-47.6%) and the estimated 24-week OS was 62.5% (95% CI: 45.4%-79.6%). Ten patients (34.3%) had at least one grade 3 or 4 adverse reaction and 12 patients (41.4%) required dose modifications due to toxicity. At 24 weeks, no patient had an improvement in global HRQoL and 87.5% experienced a permanent increase in physical fatigue. CONCLUSIONS: Sorafenib demonstrated non-progression at 24 weeks in 31.2% of patients. However, 41.4% of patients required dose modifications due to toxicity and no improvement in HRQoL was demonstrated. PMID- 27253173 TI - Conisation as a marker of persistent human papilloma virus infection and risk of breast cancer. AB - BACKGROUND: Human papillomavirus (HPV) infection may increase breast cancer (BC) risk. METHODS: To examine this, we used nationwide medical registries to identify all Danish women who underwent conisation to remove HPV-associated cervical precancerous lesions (n=87 782) from 1978 to 2013. We computed the absolute risk of BC and standardised incidence ratios (SIRs) and 95% confidence intervals (95% CIs) for breast cancer, based on national breast cancer incidence rates. RESULTS: Conisation was associated with slightly increased BC incidence (SIR=1.1, 95% CI=1.0-1.1), and an absolute BC risk of 7.7% (95% CI=7.3-8.1%) in 35.9 years of follow-up. BC risk was elevated throughout follow-up, especially in the first 5 years (<1 year: SIR=1.2, 95% CI=0.92-1.5; 1-5 years: SIR=1.2, 95% CI=1.1-1.3; ?5 years: SIR=1.1, 95% CI=1.0-1.1). Women who underwent conisation and had autoimmune disease had elevated BC risk after 5 years of follow-up (SIR=1.4, 95% CI=1.0-1.8). CONCLUSIONS: BC risk is slightly elevated in women with persistent HPV infection, possibly due to detection bias. PMID- 27253172 TI - Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee. AB - BACKGROUND: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. METHODS: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002 2015). RESULTS: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. CONCLUSIONS: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials. PMID- 27253174 TI - Improvement of cisplatin-related renal dysfunction by synthetic ghrelin: a prospective randomised phase II trial. AB - BACKGROUND: Ghrelin, a 28-amino acid peptide predominantly produced by the stomach, exerts powerful renal protective effects by increasing levels of insulin like growth factor-1 (IGF-1). The aim of this study was to evaluate the effects of ghrelin on the incidence of renal dysfunction in patients receiving cisplatin based chemotherapy. METHODS: Forty patients with oesophageal cancer receiving cisplatin-based chemotherapy were assigned to either the ghrelin group (n=20), which received ghrelin (0.5 MUg kg(-1) h(-1)) for 5 days, or a placebo group (n=20). The primary endpoint was serum creatinine. Secondary endpoints were serum cystatin C, chemotherapy-related adverse events, changes in serum ghrelin-related hormone levels, correlation between markers of renal injury and hormone concentrations, and effects on the second cycle of chemotherapy. RESULTS: Blood acyl ghrelin, total ghrelin, and IGF-1 concentrations on day 4 were significantly higher in the ghrelin group. The renal dysfunction, serum creatinine and cystatin C levels, dose reduction, and delay in the initiation of the second cycle of chemotherapy were lower in the ghrelin group than in the control group. Serum creatinine levels were significantly correlated with serum IGF-1 levels. CONCLUSION: Continuous synthetic ghrelin administration during cisplatin-based chemotherapy attenuated renal dysfunction and harmful effects on subsequent chemotherapy, possibly by increasing IGF-1 levels. PMID- 27253175 TI - Expression signature distinguishing two tumour transcriptome classes associated with progression-free survival among rare histological types of epithelial ovarian cancer. AB - BACKGROUND: The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies. METHODS: In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information. RESULTS: We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases (P=8.24 * 10(-3)). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS (P=1.43 * 10( 3)). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005%) and WNT signalling pathway (FDR=1.46%); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86%) and toll-like receptor pathways (FDR=2.37%). CONCLUSIONS: These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies. PMID- 27253176 TI - Association between prediagnostic glucose, triglycerides, cholesterol and meningioma, and reverse causality. AB - BACKGROUND: Although meningioma is a benign tumour, it may cause significant morbidity. Obesity and diabetes are positively associated with meningioma. To evaluate the potential effects of obesity-related prediagnostic glucose, triglycerides and cholesterol on meningioma and of prediagnostic meningioma on these biomarkers, we conducted a cohort study. METHODS: We identified 41 355 individuals in the Apolipoprotein MOrtality RISk cohort with values for these biomarkers within 15 years before meningioma diagnosis, death, migration or the end of follow-up. We then estimated hazard ratios (HRs) and their interactions with time and age using Cox regression. RESULTS: Meningioma was diagnosed in 181 women and 115 men whose median follow-up time was 7 years. Fasting serum glucose level was inversely related to meningioma among women (Ptrend=0.0006) but not men (Ptrend=0.24). Prediagnostic diabetes was inversely related to meningioma in both sexes combined (HR=0.45, 95% confidence interval (CI) 0.29-0.71), as was serum cholesterol within the year before diagnosis (HR=0.50, 95% CI 0.34-0.72). CONCLUSIONS: Paradoxically, hyperglycaemia is inversely associated with meningioma in women. This finding does not necessarily negate the positive role of obesity or diabetes in meningioma development; rather, it may indicate that their effects depend on the stage of development. Furthermore, the prediagnostic tumour may reduce serum cholesterol levels. PMID- 27253178 TI - Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh. AB - OBJECTIVE: To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal-weight children aged 6-24 months in urban Bangladesh. METHODS: Cohorts of 446 normal-weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow-up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status. RESULTS: Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate to-severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal-weight children, insufficient vitamin D status and moderate-to-severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only. CONCLUSION: This study demonstrates for the first time that normal-weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate-to-severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal-weight children. PMID- 27253177 TI - Risk of venous thromboembolism in people with lung cancer: a cohort study using linked UK healthcare data. AB - BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable cause of death in people with lung cancer. Identification of those most at risk and high risk periods may provide the opportunity for better targeted intervention. METHODS: We conducted a cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics and Cancer Registry data. Our cohort comprises 10 598 people with lung cancer diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, tumour and treatment-related factors (time-varying effects of chemotherapy and surgery) independently affected VTE risk. We also determined the effect of a VTE diagnosis on the survival of people with lung cancer. RESULTS: People with lung cancer had an overall VTE incidence of 39.2 per 1000 person-years (95% confidence interval (CI), 35.4-43.5), though rates varied depending on the patient group and treatment course. Independent factors associated with increased VTE risk were metastatic disease (hazard ratio (HR)=1.9, CI 1.2-3.0 vs local disease); adenocarcinoma subtype (HR=2.0, CI 1.5 2.7, vs squamous cell; chemotherapy administration (HR=2.1, CI 1.4-3.0 vs outside chemotherapy courses); and diagnosis via emergency hospital admission (HR=1.7, CI 1.2-2.3 vs other routes to diagnosis). Patients with VTE had an approximately 50% higher risk of mortality than those without VTE. CONCLUSIONS: People with lung cancer have especially high risk of VTE if they have advanced disease, adenocarcinoma or are undergoing chemotherapy. The presence of VTE is an independent risk factor for death. PMID- 27253179 TI - Identification of putative Z-ring-associated proteins, involved in cell division in human pathogenic bacteria Helicobacter pylori. AB - Cell division in bacteria is initiated by FtsZ, which forms a Z ring at the middle of the cell, between the nucleoids. The Z ring is stabilized by Z ring associated proteins (Zaps), which crosslink the FtsZ filaments and provide strength. The deletion of Zaps leads to the elongation phenotype with an abnormal Z ring. The components of cell division in Helicobacter pylori are similar to other gram negative bacteria except for the absence of few components including Zaps. Here, we used HHsearch to identify homologs of the missing cell division proteins and got potential hits for ZapA and ZapB, as well as for few other cell division proteins. We further validated the function of the putative ZapA homolog by genetic complementation, immuno-colocalization and biochemical analysis. PMID- 27253180 TI - Cinnamon extract reduces VEGF expression via suppressing HIF-1alpha gene expression and inhibits tumor growth in mice. AB - Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cinnamon (CE) was a potent inhibitor of VEGF production in human cancer cells and suggested inhibition might be mediated through the suppression of HIF-1alpha gene expression and protein synthesis. Furthermore, CE treatment was found to inhibit expression and phosphorylation of STAT3 and AKT, which are key factors in the regulation of HIF-1alpha expression, and significantly reduce angiogenesis potential of cancer cells by migration assay. Consistent with these results, we observed significant suppression of VEGF expression, blood vessel formation, and tumor growth in a human ovarian tumor model in mice treated with CE. Cinnamaldehyde, a major component in cinnamon, was identified as one active component in CE that inhibits VEGF expression. Taken together, our findings provide a novel mechanism underlying anti-angiogenic and anti-tumor actions of CE and support the potential use of CE in cancer prevention and treatment. (c) 2016 Wiley Periodicals, Inc. PMID- 27253181 TI - Clinical epidemiology of acute hepatitis C in South America. AB - There is scarce data pertaining to acute hepatitis C (aHC) infection in South America. We aimed to describe clinical characteristics and evolution of aHC in a South American cohort. A retrospective survey was conducted at 13 hepatology units. All patients >=16 years old with aHC diagnosis were included. Demographic, clinical and outcome information were registered in a standardized ad hoc questionnaire. Sixty-four patients were included. The majority were middle-aged (median age: 46 years) and female (65.6%); most of them were symptomatic at diagnosis (79.6%). HCV-1 was the most prevalent genotype (69.2%). Five patients had liver failure: three cases of severe acute hepatitis, one case of fulminant hepatitis and one case of acute-on-chronic liver failure. Nosocomial exposure was the most prevalent risk factor. Evolution was assessed in 46 patients. In the untreated cohort, spontaneous resolution occurred in 45.8% and was associated with higher values of AST/ALT and with the absence of intermittent HCV RNA viremia (P = 0.01, 0.05, and 0.01, respectively). In the treated cohort, sustained virological response was associated with nosocomial transmission and early treatment initiation (P = 0.04 each). The prevalence of nosocomial transmission in this South-American cohort of aHC stresses the importance of following universal precautions to prevent HCV infection. J. Med. Virol. 89:276 283, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27253182 TI - Educating Mental Health Clinicians About Sensory Modulation to Enhance Clinical Practice in a Youth Acute Inpatient Mental Health Unit: A Feasibility Study. AB - There is an emergence of literature describing effective sensory modulation (SM) interventions to de-escalate violence and aggression among mental health inpatients. However, the evidence is limited to adult settings, with the effect of SM in youth acute settings unknown. Yet, before SM may be used as a de escalation intervention in youth acute settings, multidisciplinary staff need to be educated about and supported in the clinical application of SM. In the current study, an online SM education package was developed to assist mental health staff understand SM. This was blended with action learning sets (ALS), small group experiential opportunities consisting staff and consumers to learn about SM resources, and the support of SM trained nurses. The aims of the study were to evaluate the effectiveness of this SM education intervention in (a) transferring knowledge of SM to staff, and (b) translating this knowledge into practice in a youth acute inpatient mental health unit. A mixed methods research design with an 11-item pre- and post-education questionnaire was used along with three-month follow-up focus groups. The SM education improved understanding about SM (all 11 items p <= 0.004, r >= 0.47). Three-months after SM education, four themes evident in the focus group data emerged about the practice and process of SM; (1) translating of learning into practice, (2) SM in practice, (3) perceptions of SM benefits, and (4) limitations of SM. A blended SM education process enhanced clinical practice in the unit, yet participants were mindful of limitations of SM in situations of distress or escalating agitation. PMID- 27253183 TI - How a Nanostructure's Shape Affects its Lifetime in the Environment: Comparing a Silver Nanocube to a Nanoparticle When Dispersed in Aqueous Media. AB - Herein, we detail how the morphology of a nanomaterial affects its environmental lifetime in aquatic ecosystems. In particular, we focus on the cube and particle nanostructures of Ag and age them in various aquatic mediums including synthetic hard water, pond water, and seawater. Our results show that in the synthetic hard water and pond water cases, there was little difference in the rate of morphological changes as determined by UV-vis spectroscopy. However, when these samples were analyzed with transmission electron microscopy, radically different mechanisms in the loss of their original nanostructures were observed. Specifically, for the nanocube we observed that the corners of the cubes had become more rounded, whereas the aged nanoparticles formed large aggregates. Most interestingly, when the seawater samples were analyzed, the nanocubes showed a substantially higher stability in maintaining the nano length scale in comparison to nanoparticles overtime. Moreover, high-resolution transmission electron microscopy analysis allowed us to determine that Ag+ ions diffused away from both the edge and from the faces of the cube, whereas the nanoparticle rapidly aggregated under the harsh seawater conditions. PMID- 27253185 TI - Ultralong Persistent Room Temperature Phosphorescence of Metal Coordination Polymers Exhibiting Reversible pH-Responsive Emission. AB - Ultra-long-persistent room temperature phosphorescence (RTP) materials have attracted much attention and present various applications in illumination, displays, and the bioimaging field; however, the persistent RTP is generally from the inorganic phosphor materials to date. Herein, we show that the metal coordination polymers (CPs) could be new types of emerging long-lived RTP materials for potential sensor applications. First, two kinds of Cd-based CPs, Cd(m-BDC)(H2O) (1) and Cd(m-BDC)(BIM) (2) (m-BDC = 1,3-benzenedicarboxylic acid; BIM = benzimidazole), were obtained through a hydrothermal process, and the samples were found to exhibit two-dimensional layered structures, which are stabilized by interlayer C-H...pi interaction and pi...pi interaction, respectively. The CPs show unexpected second-time-scale ultra-long-persistent RTP after the removal of UV excitation, and this persistent emission can be detected easily on a time scale of 0-10 s. The CPs also feature a tunable luminescence decay lifetime by adjusting their coordination situation and packing fashion of ligands. Theoretical calculation further indicates that the introduction of the second ligand could highly influence the electronic structure and intermolecular electron transfer toward tailoring the RTP of the CP materials. Moreover, CP 2 exhibits well-defined pH- and temperature-dependent phosphorescence responses. Therefore, this work provides a facile way to develop new type of CPs with steady state and dynamic tuning of the RTP properties from both experimental and theoretical perspectives, which have potential applications in the areas of displays, pH/temperature sensors, and phosphorescence logic gates. On account of suitable incorporation of inorganic and organic building blocks, it can be expected that the ultra-long-persistent RTP CPs can be extended to other similar systems due to the highly tunable structures and facile synthesis routes. PMID- 27253184 TI - Can Targeted Intervention Mitigate Early Emotional and Behavioral Problems?: Generating Robust Evidence within Randomized Controlled Trials. AB - This study examined the impact of a targeted Irish early intervention program on children's emotional and behavioral development using multiple methods to test the robustness of the results. Data on 164 Preparing for Life participants who were randomly assigned into an intervention group, involving home visits from pregnancy onwards, or a control group, was used to test the impact of the intervention on Child Behavior Checklist scores at 24-months. Using inverse probability weighting to account for differential attrition, permutation testing to address small sample size, and quantile regression to characterize the distributional impact of the intervention, we found that the few treatment effects were largely concentrated among boys most at risk of developing emotional and behavioral problems. The average treatment effect identified a 13% reduction in the likelihood of falling into the borderline clinical threshold for Total Problems. The interaction and subgroup analysis found that this main effect was driven by boys. The distributional analysis identified a 10-point reduction in the Externalizing Problems score for boys at the 90th percentile. No effects were observed for girls or for the continuous measures of Total, Internalizing, and Externalizing problems. These findings suggest that the impact of this prenatally commencing home visiting program may be limited to boys experiencing the most difficulties. Further adoption of the statistical methods applied here may help to improve the internal validity of randomized controlled trials and contribute to the field of evaluation science more generally. TRIAL REGISTRATION: ISRCTN Registry ISRCTN04631728. PMID- 27253186 TI - Clinical case report: a rare cause of acute kidney failure - tissue is the issue. AB - A patient was admitted to the medical emergency department by his family physician. His complaints were weakness and fatigue for more than one week. Four days before admission, he went to his general practitioner for these complaints and also for painful elbows. His physician prescribed diclofenac and esomeprazole. Upon presentation, he had high systolic/diastolic blood pressure (>180/>90 mm Hg, measured repeatedly), and otherwise normal parameters. He had gained 6.5 kg in body weight. Clinical examination was normal, except for very mild bilateral malleolar edema. Routine blood tests showed a strongly elevated serum creatinine, hyperkalemia, and elevated lactate dehydrogenase. Haptoglobin levels were normal. Urinalysis showed a normal sediment, urine and blood cultures remained sterile. Ophthalmoscopy was completely normal, as was a routine chest X ray. Renal ultrasound demonstrated kidneys with a diameter of 13 cm. Due to uncontrollable hypertension, our patient was hospitalized at the intensive care department where intravenous nifedipine was started, with good instantaneous control of blood pressure. Because of increasing potassium levels acute hemodialysis was started within 24 h after admission. Differential diagnosis consisted of diclofenac- or esomeprazole-induced interstitial nephritis or rapidly progressive glomerulonephritis. A renal biopsy was performed within 72 h after admission. The kidney biopsy showed an overwhelming inflammatory cell infiltrate consisting of a monoclonal lymphocytic cell population. However, the numerous mitotic figures, polyploidy, and prominent nucleoli present, were indicative of a lymphoma. Additional stainings confirmed a non-Hodgkin diffuse large-cell B-cell lymphoma. Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, and prednisolone) was initiated with very good clinical and biochemical response, yet only mild recovery of kidney function. Occasionally the kidney is involved as an extranodal non-Hodgkin lymphoma (NHL) localization. However, a primary presentation of acute kidney failure due to lymphoma localization is extremely rare. Our case demonstrates that early renal biopsy is indispensable for fast and adequate diagnosis and treatment. PMID- 27253188 TI - A phenotype of IGFBP-3 knockout mice revealed by dextran sulfate-induced colitis. AB - BACKGROUND AND AIM: Insulin-like growth factor-1 (IGF-1) bioactivity has been shown to be attenuated by insulin-like growth factor binding protein-3 (IGFBP-3), one of six IGF-binding proteins. While prior work revealed no major phenotype associated with IGFBP-3 knockout mice, we explored the possibility that a phenotype could be revealed under specific conditions of gastrointestinal stress. METHODS: The dextran sodium sulfate (DSS) murine model of ulcerative colitis was used for this study. RESULTS: Insulin-like growth factor binding protein-3 knockout mice had significantly reduced colitis on exposure to DSS as measured by lower levels of pro-inflammatory cytokines IL-6 (P < 0.0001), TNF-alpha (P = 0.0035), and IL-1beta (P = 0.0112), reduced weight loss (P < 0.0001), reduced myeloperoxidase activity (P = 0.0025), and maintenance of colorectal length (P < 0.05), all relative to wild-type mice exposed to DSS. IGFBP-3 knockout mice also exhibited increased colon epithelial cell proliferation (P < 0.0001) following DSS exposure. Semi-quantitative immunohistochemistry showed greater IGF-1 receptor activation in colon epithelial cells of IGFBP-3 knockout mice compared with control mice following DSS exposure. CONCLUSION: Our data demonstrate that IGFBP-3 influences severity of DSS-induced colitis. The observations suggest that in the absence of IGFBP-3, enhanced IGF bioactivity leads to increased epithelial proliferation and mucosal barrier repair, thereby lessening inflammation. PMID- 27253187 TI - Correlation Analysis between Polysomnography Diagnostic Indices and Heart Rate Variability Parameters among Patients with Obstructive Sleep Apnea Hypopnea Syndrome. AB - Heart rate variability (HRV) can reflect the changes in the autonomic nervous system (ANS) that are affected by apnea or hypopnea events among patients with obstructive sleep apnea hypopnea syndrome (OSAHS). To evaluate the possibility of using HRV to screen for OSAHS, we investigated the relationship between HRV and polysomnography (PSG) diagnostic indices using electrocardiography (ECG) and PSG data from 25 patients with OSAHS and 27 healthy participants. We evaluated the relationship between various PSG diagnostic indices (including the apnea hypopnea index [AHI], micro-arousal index [MI], oxygen desaturation index [ODI]) and heart rate variability (HRV) parameters using Spearman's correlation analysis. Moreover, we used multiple linear regression analyses to construct linear models for the AHI, MI, and ODI. In our analysis, the AHI was significantly associated with relative powers of very low frequency (VLF [%]) (r = 0.641, P = 0.001), relative powers of high frequency (HF [%]) (r = -0.586, P = 0.002), ratio between low frequency and high frequency powers (LF/HF) (r = 0.545, P = 0.049), normalized powers of low frequency (LF [n.u.]) (r = 0.506, P = 0.004), and normalized powers of high frequency (HF [n.u.]) (r = -0.506, P = 0.010) among patients with OSAHS. The MI was significantly related to standard deviation of RR intervals (SDNN) (r = 0.550, P = 0.031), VLF [%] (r = 0.626, P = 0.001), HF [%] (r = -0.632, P = 0.001), LF/HF (r = 0.591, P = 0.011), LF [n.u.] (r = 0.553, P = 0.004), HF [n.u.] (r = -0.553, P = 0.004), and absolute powers of very low frequency (VLF [abs]) (r = 0.525, P = 0.007) among patients with OSAHS. The ODI was significantly correlated with VLF [%] (r = 0.617, P = 0.001), HF [%] (r = 0.574, P = 0.003), LF [n.u.] (r = 0.510, P = 0.012), and HF [n.u.] (r = -0.510, P = 0.012) among patients with OSAHS. The linear models for the PSG diagnostic indices were AHI = -38.357+1.318VLF [%], MI = -13.389+11.297LF/HF+0.266SDNN, and ODI = -55.588+1.715VLF [%]. However, the PSG diagnostic indices were not related to the HRV parameters among healthy participants. Our analysis suggests that HRV parameters are powerful tools to screen for OSAHS patients in place of PSG monitoring. PMID- 27253190 TI - A general risk-based adaptive management scheme incorporating the Bayesian Network Relative Risk Model with the South River, Virginia, as case study. AB - Adaptive management has been presented as a method for the remediation, restoration, and protection of ecological systems. Recent reviews have found that the implementation of adaptive management has been unsuccessful in many instances. We present a modification of the model first formulated by Wyant and colleagues that puts ecological risk assessment into a central role in the adaptive management process. This construction has 3 overarching segments. Public engagement and governance determine the goals of society by identifying endpoints and specifying constraints such as costs. The research, engineering, risk assessment, and management section contains the decision loop estimating risk, evaluating options, specifying the monitoring program, and incorporating the data to re-evaluate risk. The 3rd component is the recognition that risk and public engagement can be altered by various externalities such as climate change, economics, technological developments, and population growth. We use the South River, Virginia, USA, study area and our previous research to illustrate each of these components. In our example, we use the Bayesian Network Relative Risk Model to estimate risks, evaluate remediation options, and provide lists of monitoring priorities. The research, engineering, risk assessment, and management loop also provides a structure in which data and the records of what worked and what did not, the learning process, can be stored. The learning process is a central part of adaptive management. We conclude that risk assessment can and should become an integral part of the adaptive management process. Integr Environ Assess Manag 2017;13:115-126. (c) 2016 SETAC. PMID- 27253191 TI - Association of type 2 diabetes susceptibility loci with peripheral nerve function in a Chinese population with diabetes. AB - AIMS/INTRODUCTION: Previous studies have suggested a possible relationship between type 2 diabetes mellitus susceptibility loci and diabetic complications. The present study aimed to investigate the associations between type 2 diabetes mellitus loci with peripheral nerve function in a Chinese population with type 2 diabetes mellitus. MATERIALS AND METHODS: A total of 1,900 type 2 diabetes mellitus patients were recruited in the study. We selected ten single nucleotide polymorphisms (SNPs) from ten type 2 diabetes mellitus susceptibility genes previously confirmed in Chinese patients. Genotyping was carried out by using a MassARRAY Compact Analyzer. Peripheral nerve function was evaluated by nerve conduction studies in all participants. The composite Z-scores for nerve conduction parameters including conduction velocity (CV), amplitude and latency were calculated, respectively. RESULTS: Rs5219 of KCNJ11 (E23K, G->A) was identified to be associated with all the parameters obtained from nerve conduction studies (Z-score of CV: beta = 0.113, P = 0.01; Z-score of amplitude: beta = 0.133, P = 0.01; Z-score of latency: beta = -0.116, P = 0.01) after adjustment for covariates including age, duration and glycated hemoglobin. Specifically, each copy of the A allele was related to better outcomes. CDKAL1 rs7756992 and TCF7L2 rs7903146 correlated with the composite Z-score of amplitude (P = 0.028 and P = 0.016, respectively), but not CV (P = 0.393 and P = 0.281, respectively) or latency (P = 0.286 and P = 0.273, respectively). There were no significant associations between the other seven SNPs and peripheral nerve function. CONCLUSIONS: Rs5219 at KCNJ11 (E23K) was associated with peripheral nerve function in a Chinese population with type 2 diabetes mellitus, suggesting shared genetic factors for type 2 diabetes mellitus and diabetic polyneuropathy in this population. PMID- 27253192 TI - Anti-infective Surface Coatings: Design and Therapeutic Promise against Device Associated Infections. PMID- 27253194 TI - Peak expiratory flow in healthy, young, non-active subjects in seated, supine, and prone postures. AB - OBJECTIVE: To compare the PEFs in healthy, young, non-active subjects in seated, supine, and prone postures. METHODS: A total of 30 healthy volunteers (15 male, mean age 22.7 years, non-smokers, sedentary) underwent a physical examination, spirometry to confirm normal pulmonary function, and PEF using the Mini-Wright Peak Flow Meter while wearing a nose clip. PEF measurements were repeated three times in each of three positions (seated, prone, and supine) in random order and differed by less than 20 L/min for a given position. Paired Student's t-tests were used to analyze the results, and the significance level was set at 5%. RESULTS: The PEF values obtained when the study participants were in a seated position (481.0 +/- 115.1 L/min) were higher than those obtained when participants were in prone (453.7 +/- 112.1 L/min) or supine (453.2 +/- 114.3 L/min) positions (p < 0.05). No significant difference in PEF values was observed between the prone and supine positions. CONCLUSION: Body posture affects PEF in healthy, young, non-active subjects. PEFs are higher when subjects are in a seated position compared to prone or supine positions, but no difference in PEF is observed between the prone and supine positions. PMID- 27253193 TI - Identification of Changes in Gene expression of rats after Sensory and Motor Nerves Injury. AB - Wallerian degeneration is a sequence of events in the distal stump of axotomized nerves. Despite large numbers of researches concentrating on WD, the biological mechanism still remains unclear. Hence we constructed a rat model with both motor and sensory nerves injury and then conducted a RNA-seq analysis. Here the rats were divided into the 4 following groups: normal motor nerves (NMN), injured motor nerves (IMN), normal sensory nerves (NSN) and injured sensory nerves (ISN). The transcriptomes of rats were sequenced by the Illumina HiSeq. The differentially expressed genes (DEGs) of 4 combinations including NMN vs. IMN, NSN vs. ISN, NMN vs. NSN and IMN vs. ISN were identified respectively. For the above 4 combinations, we identified 1666, 1514, 95 and 17 DEGs. We found that NMN vs. IMN shared the most common genes with NSN vs. ISN indicating common mechanisms between motor nerves injury and sensory nerves injury. At last, we performed an enrichment analysis and observed that the DEGs of NMN vs IMN and NSN vs. ISN were significantly associated with binding and activity, immune response, biosynthesis, metabolism and development. We hope our study may shed light on the molecular mechanisms of nerves degeneration and regeneration during WD. PMID- 27253195 TI - Complexes of carborane acids linked by strong hydrogen bonds: acidity scales. AB - Carborane acids, currently known as the strongest acis, are analyzed and compared with other species classified as superacids as well as with selected mineral acids and carbocations. Calculations (B3LYP/6-311++G(d,p) level) on these moieties as well as on their conjugate bases were performed to evaluate corresponding proton affinities. In addition, the complexes of these species with the CHB11F11(-) anion and the complexes of the conjugate bases with the trimethylammonium cation were analyzed. The scales, based on spectroscopic results, DFT energies and on the topological QTAIM (Quantum Theory of Atoms in Molecules) parameters, are introduced and discussed to order the acidity of the species analyzed here. The properties of the bond critical points corresponding to the intermolecular contacts are discussed. The majority of the results show that HCHB11F11 carborane acid is the strongest in agreement with the previous experimental studies of Reed and coworkers. Very often the abovementioned acidity scales show that carborane acids are able to protonate hydrocarbons. PMID- 27253197 TI - Non-equilibrium thermodynamics and collective vibrational modes of liquid water in an inhomogeneous electric field. AB - In this experiment liquid water is subject to an inhomogeneous electric field (?(2)Ea~ 10(10) V m(2)) using a high voltage (20 kV) point-plane electrode system. Using interferometry it was found that the application of a strong electric field gradient to water generates local changes in the refractive index of the liquid, polarizes the surface and creates a downward moving electro convective jet. A maximum temperature difference of 1 degrees C is measured in the immediate vicinity of the point electrode. Raman spectroscopy performed on water reveals an enhancement of the vibrational collective modes (3250 cm(-1)) as well as an increase in the local mode (3490 cm(-1)) energy. This bimodal enhancement indicates that the spectral changes are not due to temperature changes. The intense field gradient thus establishes an excited subpopulation of vibrational oscillators far from thermal equilibrium. Delocalization of the collective vibrational mode spatially expands this excited population beyond the microscale. Hindered rotational freedom due to electric field pinning of molecular dipoles retards the heat flow and generates a chemical potential gradient. These changes are responsible for the observed changes in the refractive index and temperature. It is demonstrated that polar liquids can thus support local non-equilibrium thermodynamic transient states critical to biochemical and environmental processes. PMID- 27253196 TI - Acceptability of Parental Financial Incentives and Quasi-Mandatory Interventions for Preschool Vaccinations: Triangulation of Findings from Three Linked Studies. AB - BACKGROUND: Childhood vaccinations are a core component of public health programmes globally. Recent measles outbreaks in the UK and USA have prompted debates about new ways to increase uptake of childhood vaccinations. Parental financial incentives and quasi-mandatory interventions (e.g. restricting entry to educational settings to fully vaccinated children) have been successfully used to increase uptake of childhood vaccinations in developing countries, but there is limited evidence of effectiveness in developed countries. Even if confirmed to be effective, widespread implementation of these interventions is dependent on acceptability to parents, professionals and other stakeholders. METHODS: We conducted a systematic review (n = 11 studies included), a qualitative study with parents (n = 91) and relevant professionals (n = 24), and an on-line survey with embedded discrete choice experiment with parents (n = 521) exploring acceptability of parental financial incentives and quasi-mandatory interventions for preschool vaccinations. Here we use Triangulation Protocol to synthesise findings from the three studies. RESULTS: There was a consistent recognition that incentives and quasi-mandatory interventions could be effective, particularly in more disadvantaged groups. Universal incentives were consistently preferred to targeted ones, but relative preferences for quasi-mandatory interventions and universal incentives varied between studies. The qualitative work revealed a consistent belief that financial incentives were not considered an appropriate motivation for vaccinating children. The costs of financial incentive interventions appeared particularly salient and there were consistent concerns in the qualitative work that incentives did not represent the best use of resources for promoting preschool vaccinations. Various suggestions for improving delivery of the current UK vaccination programme as an alternative to incentives and quasi mandates were made. CONCLUSIONS: Parental financial incentives and quasi mandatory interventions for increasing uptake of preschool vaccinations do not currently attract widespread enthusiastic support in the UK; but some potential benefits of these approaches are recognised. PMID- 27253198 TI - The Anatomy of the Global Football Player Transfer Network: Club Functionalities versus Network Properties. AB - Professional association football is a game of talent. The success of a professional club hinges largely on its ability of assembling the best team. Building on a dataset of player transfer records among more than 400 clubs in 24 world-wide top class leagues from 2011 to 2015, this study aims to relate a club's success to its activities in the player transfer market from a network perspective. We confirm that modern professional football is indeed a money game, in which larger investment spent on the acquisition of talented players generally yields better team performance. However, further investigation shows that professional football clubs can actually play different strategies in surviving or even excelling this game, and the success of strategies is strongly associated to their network properties in the football player transfer network. PMID- 27253199 TI - Decay Rate of Correlated Real-Space Delocalization Measures: Insights into Chemical Bonding and Mott Transitions from Hydrogen Chains. AB - We study in this contribution the spatial decay rate of real-space localization and delocalization indices in correlated systems. To that end, we examine Hubbard and quantum chemical models of simple cyclic hydrogen chains, showing that all descriptors of delocalization converge quickly toward the infinite chain limits. It is then shown that the localization index may be understood as a generalization of the standard order parameter in Mott insulator transitions and that the origin of the enigmatic sigmoidal profile of delocalization indices in chemical bond-breaking processes lies in the nonlinear mapping between intersite distances and correlation parameters. Although the long-range asymptotic decay of delocalization indices is exponential, we show that as the correlation parameter decreases quantum mechanical interference sets in and a switch to an oscillating pattern, related to core chemical concepts such as resonance or mesomerism, appears. PMID- 27253200 TI - Development of operating mode distributions for different types of roadways under different congestion levels for vehicle emission assessment using MOVES. AB - The Motor Vehicle Emission Simulator (MOVES) quantifies emissions as a function of vehicle modal activities. Hence, the vehicle operating mode distribution is the most vital input for running MOVES at the project level. The preparation of operating mode distributions requires significant efforts with respect to data collection and processing. This study is to develop operating mode distributions for both freeway and arterial facilities under different traffic conditions. For this purpose, in this study, we (1) collected/processed geographic information system (GIS) data, (2) developed a model of CO2 emissions and congestion from observations, (3) implemented the model to evaluate potential emission changes from a hypothetical roadway accident scenario. This study presents a framework by which practitioners can assess emission levels in the development of different strategies for traffic management and congestion mitigation. IMPLICATIONS: This paper prepared the primary input, that is, the operating mode ID distribution, required for running MOVES and developed models for estimating emissions for different types of roadways under different congestion levels. The results of this study will provide transportation planners or environmental analysts with the methods for qualitatively assessing the air quality impacts of different transportation operation and demand management strategies. PMID- 27253201 TI - Morphological and Molecular Identification of the New Species, Trichodina pseudoheterodentata sp. n. (Ciliophora, Mobilida, Trichodinidae) from the Channel Catfish, Ictalurus punctatus, in Chongqing China. AB - It is difficult to differentiate similar trichodinids solely based on morphological examination, thus other identification methods, such as molecular identification, are necessary for identification. One mobilid ciliate named Trichodina pseudoheterodentata sp. n. was isolated from the gills of channel catfish, Ictalurus punctatus, in Chongqing, China. In the present study, its SSU rDNA was sequenced for the first time. Based on the results from both morphological identification and SSU rDNA sequencing, the new species was identified and compared with similar species. The morphological analysis revealed that T. pseudoheterodentata is a large Trichodina species (cell diameter 73.0 82.5 MUm) and possesses robust denticles with broad blades and well-developed blade connections. Characterization of its primary and secondary SSU rDNA structures indicated that T. pseudoheterodentata was distinctly different from congeneric species in H12, H15, E10_1, and V4 regions. Phylogenetic analysis revealed that the genetic distances among the new species and similar species reached interspecific levels, furthermore, the phylogenetic study also validated the identification of T. pseudoheterodentata and its placement in the genus Trichodina. PMID- 27253203 TI - Intermolecular Interactions of a Chiral Amine Borane Adduct Revealed by VCD Spectroscopy. AB - Amine boranes feature strong hydrogen bonding acceptor and donor moieties in close proximity, leading, for instance, to dihydrogen bonding driven self aggregation. In this work, the infrared (IR) and vibrational circular dichroism (VCD) spectra of the bulky bis(alpha-phenylethyl)amine borane 1 in chloroform and acetonitrile solution are reported. By comparison with calculated spectra, the VCD spectral features observed in chloroform solution can clearly be associated with the presence of monomeric species. A shift of the conformational preferences occurs when changing the solvent to acetonitrile, which can only be deduced from the VCD spectral signatures but not from the IR spectrum. Using variable temperature IR and VCD spectroscopy, the dihydrogen bonded dimeric species is characterized experimentally at -50 degrees C and theoretically by means of density functional theory calculations. PMID- 27253202 TI - Aligning organizational priorities with ARC to improve youth mental health service outcomes. AB - OBJECTIVE: The Availability, Responsiveness, and Continuity (ARC) organizational intervention is designed to improve community-based youth mental health services by aligning organizational priorities with 5 principles of effective service organizations (i.e., mission driven, results oriented, improvement directed, relationship centered, participation based). This study assessed the effect of the ARC intervention on youth outcomes and the mediating role of organizational priorities as a mechanism linking the ARC intervention to outcomes. METHOD: Fourteen community-based mental health agencies in a midwestern metropolis along with 475 clinicians and 605 youth (ages 5-18) served by those agencies were randomly assigned to the 3-year ARC intervention or control condition. The agencies' priorities were measured with the ARC Principles Questionnaire (APQ) completed by clinicians at the end of the intervention. Youth outcomes were measured as total problems in psychosocial functioning described by their caregivers using the Shortform Assessment for Children (SAC) at 6 monthly intervals. RESULTS: The rate of improvement in youths' psychosocial functioning in agencies assigned to the ARC condition was 1.6 times the rate of improvement in agencies assigned to the control condition, creating a standardized difference in functioning of d = .23 between the 2 groups at the 6-month follow-up. The effect on youth outcomes was fully mediated by the alignment of organizational priorities described in the 5 ARC principles (d = .21). CONCLUSION: The ARC organizational intervention improves youth outcomes by aligning organizational priorities with the 5 ARC principles. The findings suggest that organizational priorities explain why some community mental health agencies are more effective than others. (PsycINFO Database Record PMID- 27253204 TI - Physical Activity, Sensation Seeking, and Aggression as Injury Risk Factors in Young Swiss Men: A Population-Based Cohort Study. AB - BACKGROUND: This study investigates the relationships between physical activity (PA), sports participation and sensation seeking or aggression and injury risk in young men. METHODS: A representative cohort study was conducted with 4686 conscripts for the Swiss army. Risk factors assessed at baseline were PA, the frequency of sports participation, sensation seeking, and aggression. The number of injuries during the past 12 months was reported 16 months after baseline. Exposure to moderate-tovigorous physical activity (MVPA) was estimated based on baseline PA. RESULTS: Among conscripts, 48.5% reported at least 1 injury for the past 12 months. After accounting for exposure to MVPA, the most inactive individuals (reference group) had the highest injury risk and those with high levels of PA and weekly sports participation the lowest (Poisson regression analysis: incidence rate ratio = 0.14 [0.12-0.16]). Independent of activity level, sensation seeking increased cumulative injury incidence significantly (Logistic regression analysis [injured vs. not injured]: odds ratio = 1.29 [1.02 1.63]) and incidence rates marginally. Aggression was marginally associated only with cumulative injury incidence and only in those participating in daily sports. CONCLUSIONS: When accounting for exposure to PA, being inactive is a strong injury risk factor in young men, whereas the roles of the personality variables are less clear. PMID- 27253205 TI - Zika Virus, Microcephaly, and Ocular Findings. PMID- 27253206 TI - Family Interactions and Developmental Risk Associated With Early Cognitive Delay: Influences on Children's Behavioral Competence. AB - Family interactions can be important contributors to the development of child psychopathology, yet the mechanisms of influence are understudied, particularly for populations at risk. This prospective longitudinal study addresses differences in whole family interactions in 194 families of young children with and without early-identified developmental risk associated with cognitive delay. The influence of family interactions on children's later externalizing behaviors, internalizing behaviors, and social skills was examined, and developmental risk was tested as a potential moderator of these relations. Results indicated that the presence of cognitive developmental risk was linked to higher levels of family control than in families of typically developing children, but groups did not differ on dimensions of cohesion, warmth, organization, or conflict. Observed cohesion and organization were associated with better social skills for all children, regardless of risk status. Significant interactions emerged, indicating that higher levels of conflict and control were associated with higher levels of behavior problems, but only for families of typically developing children. These findings underscore the importance of family-level assessment in understanding the development of children's behavior and suggest the need for deeper analysis of the nuances of family process over time. PMID- 27253207 TI - Fluorescence Methods for Probing G-Quadruplex Structure in Single- and Double Stranded DNA. AB - Interest in exploring G-quadruplex (G4) structures in nucleic acids is growing as it becomes more widely recognized that these structures have many interesting biological roles and chemical properties. Probing the G4-forming potential of DNA with dimethyl sulfate, polymerase stop assays, or nuclease digestion are three commonly used techniques that usually employ radio-isotopic labels for visualization. However, as fluorescent labeling methods have grown in popularity and versatility, many laboratories have moved away from the routine use of radio isotopic methods. We have adapted traditional procedures for structural analysis of G4-forming DNA sequences by using fluorescent labels and capillary electrophoresis and demonstrate their application to well-studied G4 structures, including c-MYC PU27 G4. The three fluorescent assays described here allow interrogation of G4 structures in double- and single-stranded DNA substrates, using either chemical or enzymatic cleavage. When combined, these techniques can provide valuable information for the investigation of G4 topology and structure, as well as visualizing any structural effects caused by interaction of quadruplexes with the complementary C-rich DNA strand. PMID- 27253208 TI - Influence of Perspective of Action Observation Training on Residual Limb Control in Naive Prosthesis Usage. AB - Prior work in amputees and partial limb immobilization have shown improved neural and behavioral outcomes in using their residual limb with prosthesis when undergoing observation-based training with a prosthesis-using actor compared to an intact limb. It was posited that these improvements are due to an alignment of user with the actor. It may be affected by visual angles that allow emphasis of critical joint actions which may promote behavioral changes. The purpose of this study was to examine how viewing perspective of observation-based training effects prosthesis adaptation in naive device users. Twenty nonamputated prosthesis users learned how to use an upper extremity prosthetic device while viewing a training video from either a sagittal or coronal perspective. These views were chosen as they place visual emphasis on different aspects of task performance to the device. The authors found that perspective of actions has a significant role in adaptation of the residual limb while using upper limb prostheses. Perspectives that demonstrate elbow adaptations to prosthesis usage may enhance the functional motor outcomes of action observation therapy. This work has potential implications on how prosthetic device operation is conveyed to persons adapting to prostheses through action observation based therapy. PMID- 27253210 TI - Inflammatory cytokines influence measures of white matter integrity in Bipolar Disorder. AB - BACKGROUND: Bipolar Disorder (BD) is associated with elevated biomarkers of cell mediated immune activation and inflammation and with signs of widespread disruption of white matter (WM) integrity in adult life. Consistent findings in animal models link WM damage in inflammatory diseases of the brain and serum levels of cytokines. METHODS: With an exploratory approach, we tested the effects of 22 serum analytes, including pro- and anti-inflammatory cytokines and neurotrophic/hematopoietic factors, on DTI measures of WM microstructure in a sample of 31 patients with a major depressive episode in course of BD. We used whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial (AD), radial (RD), and mean diffusivity (MD), and fractional anisotropy (FA). RESULTS: The inflammation-related cytokines TNF-alpha, IL-8, IFN-gamma and IL-10, and the growth factors IGFBP2 and PDGF-BB, shared the same significant associations with lower FA, and higher MD and RD, in large overlapping networks of WM fibers mostly located in the anterior part of the brain and including corpus callosum, cingulum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi, uncinate, forceps, corona radiata, thalamic radiation, internal capsule. CONCLUSIONS: Higher RD is thought to signify increased space between fibers, suggesting demyelination or dysmyelination. The pattern of higher RD and MD with lower FA suggests that inflammation-related cytokine and growth factor levels inversely associate with integrity of myelin sheaths. The activated inflammatory response system might contribute to BD pathophysiology by hampering structural connectivity in critical cortico-limbic networks. PMID- 27253209 TI - Predicting Allosteric Effects from Orthosteric Binding in Hsp90-Ligand Interactions: Implications for Fragment-Based Drug Design. AB - A key question in mapping dynamics of protein-ligand interactions is to distinguish changes at binding sites from those associated with long range conformational changes upon binding at distal sites. This assumes a greater challenge when considering the interactions of low affinity ligands (dissociation constants, KD, in the MUM range or lower). Amide hydrogen deuterium Exchange mass spectrometry (HDXMS) is a robust method that can provide both structural insights and dynamics information on both high affinity and transient protein-ligand interactions. In this study, an application of HDXMS for probing the dynamics of low affinity ligands to proteins is described using the N-terminal ATPase domain of Hsp90. Comparison of Hsp90 dynamics between high affinity natural inhibitors (KD ~ nM) and fragment compounds reveal that HDXMS is highly sensitive in mapping the interactions of both high and low affinity ligands. HDXMS reports on changes that reflect both orthosteric effects and allosteric changes accompanying binding. Orthosteric sites can be identified by overlaying HDXMS onto structural information of protein-ligand complexes. Regions distal to orthosteric sites indicate long range conformational changes with implications for allostery. HDXMS, thus finds powerful utility as a high throughput method for compound library screening to identify binding sites and describe allostery with important implications for fragment-based ligand discovery (FBLD). PMID- 27253211 TI - Significantly improved neurocognitive function in major depressive disorders 6 weeks after ECT. AB - BACKGROUND: Cognitive side effects may occur after electroconvulsive treatment (ECT) in depressive disorder patients. Previous studies have been limited by small numbers of cognitive functions assessed. The present study reports the first results from a prospective project monitoring cognitive effects of ECT using a comprehensive neuropsychological test battery and subjective report of everyday cognitive function. METHODS: Thirty-one patients with major depressive disorder were assessed with the MATRICS Consensus Cognitive Battery (MCCB). Subjective cognitive complaints were described with the Everyday Memory Questionnaire (EMQ). Severity of depression symptoms were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS). These assessments were performed prior to and 6 weeks after non-standardized ECT. RESULTS: Compared to baseline, the mean depression severity level was nearly halved and there were significant improvements in mean levels of Speed of Processing, Attention/Vigilance, and Visual Learning 6 weeks after ECT. The other cognitive domains were not altered from baseline. There was no significant change in subjective cognitive complaints. At baseline, there were several significant correlations between the MADRS and MCCB scores. There was no strong association between the EMQ and MCCB scores at either assessment point, but the post-ECT EMQ score was significantly correlated with depression severity. LIMITATIONS: Major limitations were low N and lack of uniform ECT procedure. CONCLUSIONS: There was significant improvement in Speed of Processing, Attention/Vigilance, and Visual Learning 6 weeks after ECT. Cognitive tests scores were related to severity of depression, but not to subjective memory complaints. PMID- 27253212 TI - Psychometric validation of the 16 Item Quick Inventory of Depressive Symptomatology Self-Report Version (QIDS-SR16) in military veterans with PTSD. AB - BACKGROUND: The Quick Inventory of Depressive Symptomatology-Self Report (QIDS SR16) is one example of a screening tool for depression, which has been utilized extensively following validation in a number of clinical populations. Despite the strengths of the QIDS-SR16, it has not been validated in military veterans, a particularly unique population considering their exposure to trauma and high rate of psychiatric comorbidities. The current report describes a psychometric validation of the QIDS-SR16 in a sample of United States military veterans diagnosed with military-related PTSD. METHODS: Participants (n=240) were administered the QIDS-SR16 and one of two gold-standard semi-structured interviews to establish diagnosis of a current Major Depressive Episode (MDE). The ability to discriminate between individuals with and without a current MDE using the QIDS-SR16 was tested with a stepwise logistic regression. Additionally, an optimal cutoff score for the QIDS-SR16 was established. RESULTS: The QIDS-SR16 was able to reliabily discriminate between individuals with and without a current MDE. The optimal cutoff score of the QIDS-SR16 for a current MDE was 13, with a sensitivity of 77.55% and specificity of 56.25%. LIMITATIONS: Limitations of this study included underrepresentation of some racial/ethnic groups, the inability to disentangle the potential influence of trauma type and gender on results, and the use of two diagnostic interviews to diagnose current MDE. DISCUSSION: The QIDS SR16 can be effectively utilized in military veterans with comorbid PTSD. However, the calculated cutoff score for this population was higher than the cutoff score for the general population. This could result from the overlap between PTSD and MDE symptoms. PMID- 27253214 TI - The long-term outcomes of an effectiveness trial of group versus individual psychoeducation for bipolar disorders. AB - BACKGROUND: In this effectiveness trial we compared the long-term effects on hospitalizations of group psychoeducation (GP) versus individual psychoeducation (IP) for a heterogeneous sample of patients with BD recruited from general clinical settings. METHODS: Eighty-five patients with BD were randomized to receive 10 weekly sessions of GP followed by 8 booster-sessions over the next two years, or three sessions of IP. Time to first admission over the course of GP was the primary outcome measure, with additional outcomes examining the use of psychiatric services over about 8 years. RESULTS: Patients allocated to GP had longer survival time compared to IP over 27 months (p<0.05). There were also group differences in survival time over 8 years, but treatment allocation alone was no longer a significant predictor of survival time (p=0.07). There was an interaction between group (GP/IP) and harmful substance use (HSU), such that GP cases with comorbid HSU had the shortest survival time, whilst GP cases without HSU survived the longest (p=0.02). Also, GP cases had a small but significant reduction in hospital use compared with IP (p=0.04). LIMITATIONS: We did not have a 'pure' treatment as usual group. Wide confidence intervals for some of the odds ratios suggest that the findings need to be treated with some caution. Insufficient sample size for more detailed subgroup analyses. CONCLUSIONS: GP is superior to IP in delaying hospitalizations in a clinically representative population. However, GP did not prevent or delay admissions in BD patients with HSU. PMID- 27253213 TI - Mood and motor activity in euthymic bipolar disorder with sleep disturbance. AB - BACKGROUND: The aims of this observational study of patients with euthymic bipolar disorder and sleep disturbance were to 1) compare characteristics related to mood and sleep between two groups with stable and unstable rest-activity cycles and 2) detect between-group differences in motor activity patterns. METHODS: 43 patients wore an actigraph for 6-8 days while reporting daily mood and sleep. Patients were defined as having an unstable rest-activity cycle if their diurnal active period duration presented variation above 2h from the mean during one week: 22 patients had stable and 21 unstable rest-activity cycles. Mood variability was defined as at least moderate symptoms and a change across two levels on a 7-point mood scale during one week. RESULTS: Patients with unstable rest-activity cycles were younger (37 vs. 48 years, p=0.01) and displayed more mood variability (p=0.02). Ten of 11 patients diagnosed with delayed sleep phase disorder were in the unstable group (p<0.01), and the unstable group had later and more variable get-up-times and bedtimes. In actigraphy recordings, the mean activity counts per minute did not differ between groups, but the minute-to-minute variability was elevated (p=0.04) and increased relative to the overall variability (p=0.03). LIMITATIONS: A relatively small study sample and a 1-week study period prevent exploration of long-term clinical implications of results. CONCLUSIONS: A subgroup of euthymic patients with bipolar disorder displayed unstable rest-activity cycles combined with mood variability and motor activity patterns that resemble findings in affective episodes. PMID- 27253215 TI - The relationship of self-compassion and depression: Cross-lagged panel analyses in depressed patients after outpatient therapy. AB - BACKGROUND: Previous cross-sectional studies suggest that self-compassion and depressive symptoms are consistently negatively associated. Although it is often implicitly assumed that (a lack of) self-compassion precedes depressive symptoms, so far no study has tested whether (lack of) self-compassion is a cause or a consequence of depressive symptoms, or both. METHOD: To examine such reciprocal effects, we used data of 125 depressed outpatients after a time limited cognitive behavioral psychotherapy. We assessed self-compassion and depressive symptoms via self-report measures and the presence of a major depressive episode directly after therapy, as well as 6 and 12 months later. RESULTS: Cross-lagged panel analyses indicated that (lack of) self-compassion significantly predicted subsequent depressive symptoms while controlling for autoregressive effects, whereas depressive symptoms did not predict subsequent levels of self-compassion. This was also the case for the relationship between self-compassion and the presence of a major depressive episode. The same patterns also occurred when we separately tested the reciprocal effects for two composite sub-measures of either positive or negative facets of self-compassion. LIMITATIONS: Causality cannot be inferred from our results. Depressive symptoms and self-compassion could still be causally unrelated, and a third variable could account for their negative association. CONCLUSIONS: These findings support the notions that (a lack of) self-compassion could serve as a vulnerability factor for depression and that cultivating self-compassion may deserve a focus in depression prevention programs or treatments. PMID- 27253216 TI - Cognitive effects of transcranial direct current stimulation in depression: Results from the SELECT-TDCS trial and insights for further clinical trials. AB - BACKGROUND: Cognitive dysfunction treatment remains an unmet clinical need in major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) may improve cognitive symptoms in MDD. Our aim was to investigate the cognitive effects of tDCS in the Sertraline vs. Electric Current Therapy for Treating Depression Clinical Study (SELECT-TDCS). We also explored whether tDCS could have mood-independent cognitive effects. METHODS: One hundred twenty MDD patients aged from 18 to 65 years received 12 sessions of active/sham tDCS (2mA for 30min) and real/placebo 50mg/d sertraline over 6 weeks in a factorial trial. We analyzed whether changes in performance of neuropsychological tests (Trail Making, Digit Span, Stroop Task, Mini-Mental Status Exam and Montreal Cognitive Assessment) occurred over time, according to treatment group and depression improvement. Exploratory analyses were carried out to verify the influence of clinical and demographic variables on the outcomes. RESULTS: Cognitive improvement was showed in most tests used, although they occurred regardless of intervention type and depression improvement. Further exploratory analyses revealed that clinical response and education level could have mediated pro-cognitive tDCS effects on some of the tests used. LIMITATIONS: The neuropsychological battery used might not have been sensitive to detect tDCS-induced effects on cognition. Lack of simultaneous cognitive training during application may have also limited its cognitive effects. CONCLUSIONS: We found no evidence of beneficial or deleterious cognitive effects of tDCS as a treatment for depression. We discussed clinical trial design considerations for further tDCS studies assessing cognitive effects, including sample and outcomes considerations. PMID- 27253217 TI - Quality of life in youth with bipolar disorder and unaffected offspring of parents with bipolar disorder. AB - BACKGROUND: There have been few studies investigating quality of life (QoL) in pediatric bipolar disorder (BD) patients and none comparing it with that observed in unaffected offspring of parents with BD and healthy controls. METHODS: The self-report Youth Quality of Life Instrument-Research version (YQoL-R) was administered in 26 pediatric BD patients, 17 unaffected offspring of parents with BD, and 24 individuals with no history of DSM-IV Axis I psychiatric disorders. All diagnoses were determined through interviews based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. RESULTS: There were statistical differences among the groups for all YQoL-R domains. Pairwise comparisons showed that perceived QoL was significantly worse in the BD group than in the unaffected offspring and healthy subjects, a difference that persisted even when only euthymic subjects were analyzed. There were no significant differences between the unaffected offspring and healthy subjects for any YQoL-R domain. LIMITATIONS: Our sample was small. There was no QoL report from subjects parents nor data about family environment or BD parents' mood state. CONCLUSIONS: There is a need for studies to investigate in greater detail the relationship between QoL and psychological resilience, particularly in the unaffected offspring of parents with BD. PMID- 27253218 TI - The ebb and flow of the wish to live and the wish to die among suicidal military personnel. AB - BACKGROUND: The relative balance between the wish to live and the wish to die (i.e., suicidal ambivalence) is a robust predictor of suicidal behavior and may be a mechanism underlying the effectiveness of treatments that reduce suicidal behaviors. To date, however, few studies have explored possible mechanisms of action in these treatments. METHOD: Active duty Soldiers (N=152) with a recent suicide attempt and/or active suicide ideation were randomized to receive brief cognitive behavioral therapy (BCBT) or treatment as usual (TAU). The Suicide Attempt Self-Injury Inventory (Linehan et al., 2006a) was used to assess the incidence of suicide attempts during the 2-year follow-up. The wish to live and the wish to die were assessed with items 1 and 2, respectively, of the Beck Scale for Suicide Ideation (Beck and Steer, 1991). RESULTS: Across both treatments, the wish to live was significantly weaker among patients who attempted suicide but the wish to die was stronger only among patients who attempted suicide in TAU. Among nonattempters, the wish to die stabilized the wish to live, but among attempters the wish to live and the wish to die were not associated with each other. In BCBT the wish to live destabilized the wish to die among nonattempters. LIMITATIONS: Self-report methodology, predominantly male sample. CONCLUSIONS: The emergence of suicidal behavior is driven primarily by the absence of the wish to live. BCBT is associated with a unique coupling of an ambivalent wish to live and wish to die, which may suggest an underlying mechanism of action. PMID- 27253219 TI - Exercise as a treatment for depression: A meta-analysis. AB - BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) examines the efficacy of physical exercise as treatment for unipolar depression, both as an independent intervention and as an adjunct intervention to antidepressant medication. METHODS: We searched PsycINFO, EMBASE, MEDLINE, CENTRAL, and Sports Discus for articles published until November 2014. Effect sizes were computed with random effects models. The main outcome was reduction in depressive symptoms or remission. RESULTS: A total of 23 RCTs and 977 participants were included. Physical exercise had a moderate to large significant effect on depression compared to control conditions (g=-0.68), but the effect was small and not significant at follow-up (g=-0.22). Exercise compared to no intervention yielded a large and significant effect size (g=-1.24), and exercise had a moderate and significant effect compared to usual care (g=-0.48). The effects of exercise when compared to psychological treatments or antidepressant medication were small and not significant (g=-0.22 and g=-0.08, respectively). Exercise as an adjunct to antidepressant medication yielded a moderate effect (g=-0.50) that trended toward significance. LIMITATIONS: Use of the arms with the largest clinical effect instead of largest dose may have overestimated the effect of exercise. CONCLUSIONS: Physical exercise is an effective intervention for depression. It also could be a viable adjunct treatment in combination with antidepressants. PMID- 27253221 TI - Sexual activity after dysvascular lower extremity amputation. AB - OBJECTIVE: This study examined the prevalence and correlates of sexual activity among individuals experiencing their first dysvascular lower extremity amputation. DESIGN: A prospective cohort was recruited from 4 Veterans Affairs Medical Centers. Of 198 potential participants who met inclusion criteria, 113 (57%) agreed to participate within 7 days of amputation (baseline) and 6 weeks, 4 months, and 12 months post-amputation; 105 completed the sexual activity items at baseline. Measures included self-reported frequency of sexual activity; desire for more or less sexual activity; importance of sexual activity to satisfaction with life; Patient Health Questionnaire-9; Locomotor Capability Index-5; pain intensity/frequency; quality of life. RESULTS: Depending on the time period post amputation, 11%-24% reported engaging in any sexual activity, although a majority indicated that sexual activity is very important to their satisfaction with life. Frequency of sexual activity increased between 6 weeks and 4 and 12 months post amputation. In univariate analyses, older age was associated with decreased sexual activity at all time points; at 4 and 12 months, greater mobility was associated with increased sexual activity. In multivariable models, mobility was associated with sexual activity at 4 and 12 months; age and race remained associated with sexual activity at 4 and 12 months, respectively. At all time points, frequency and importance of sexual activity were significantly associated with one another. CONCLUSIONS: Although a minority of individuals engaged in any sexual activity during the study period, it remained an important factor in overall satisfaction with life. Younger age and improved mobility were associated with increased sexual activity. Rehabilitation specialists are encouraged to address sexuality and, if relevant, incorporate it into rehabilitation goals. (PsycINFO Database Record PMID- 27253220 TI - Development of Sulfonamide Photoaffinity Inhibitors for Probing Cellular gamma Secretase. AB - gamma-Secretase is a multiprotein complex that catalyzes intramembrane proteolysis associated with Alzheimer's disease and cancer. Here, we have developed potent sulfonamide clickable photoaffinity probes that target gamma secretase in vitro and in cells by incorporating various photoreactive groups and walking the clickable alkyne handle to different positions around the molecule. We found that benzophenone is preferred over diazirine as a photoreactive group within the sulfonamide scaffold for labeling gamma-secretase. Intriguingly, the placement of the alkyne at different positions has little effect on probe potency but has a significant impact on the efficiency of labeling of gamma-secretase. Moreover, the optimized clickable photoprobe, 163-BP3, was utilized as a cellular probe to effectively assess the target engagement of inhibitors with gamma secretase in primary neuronal cells. In addition, biotinylated 163-BP3 probes were developed and used to capture the native gamma-secretase complex in the 3 [(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO) solubilized state. Taken together, these next generation clickable and biotinylated sulfonamide probes offer new tools to study gamma-secretase in biochemical and cellular systems. Finally, the data provide insights into structural features of the sulfonamide inhibitor binding site in relation to the active site and into the design of clickable photoaffinity probes. PMID- 27253222 TI - Parental reflective functioning and the neural correlates of processing infant affective cues. AB - Parental reflective functioning refers to the capacity for a parent to understand their own and their infant's mental states, and how these mental states relate to behavior. Higher levels of parental reflective functioning may be associated with greater sensitivity to infant emotional signals in fostering adaptive and responsive caregiving. We investigated this hypothesis by examining associations between parental reflective functioning and neural correlates of infant face and cry perception using event-related potentials (ERPs) in a sample of recent mothers. We found both early and late ERPs were associated with different components of reflective functioning. These findings suggest that parental reflective functioning may be associated with the neural correlates of infant cue perception and further support the value of enhancing reflective functioning as a mechanism in parenting intervention programs. PMID- 27253223 TI - Suppression of alpha-Amylase inactivation in the presence of ethanol: Application of a two-step model. AB - A number of years ago we reported a two-step inactivation mechanism for alpha amylase (enzyme) on the basis of theoretical and experimental studies in aqueous solutions. In the first step the metal (Ca2+ ) ion dissociates reversibly from the enzyme followed by an irreversible thermal inactivation of the apoenzyme. In this study we report inactivation of the enzyme in the presence of ethanol-water solutions. We noticed that as the concentration of ethanol in the aqueous solution is increased, the thermal inactivation of the enzyme is suppressed with almost no inactivation (in 1 h, 30 degrees C) when 50% alcohol is present in the solution. These results are explained by the two-step inactivation model. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1271-1275, 2016. PMID- 27253226 TI - Phonological awareness intervention and attention efficiency in children at risk: evidence of effectiveness on visual attention. AB - Using a pretest and posttest comparison group design, this 20 weeks study investigated the effects of a phonological awareness training program (PATP) on attention efficiency (AE) in 57 children (age = 5 to 6 years) at risk. The experimental group received the PATP (EG; n=30). We obtained pretest and posttest measures of phonological awareness and AE. The ANOVA showed significant interaction effects of the PATP and time on phonological awareness and AE. For both groups, posttest AE score means were higher than pretest score means. Pretest measures showed that the AE score mean for the EG was lower than that for the Control Group (CG; n=31); whereas posttest data showed no between group differences. Contrast analysis showed that the EG gained a greater level of phonological awareness ability and AE over CG. Our results indicate that children's attention efficiency not only improved as they developed, but also increased by means of a PATP. PMID- 27253225 TI - Questionnaire validation - PEACH on Brazilian Portuguese. AB - PURPOSE: Translate, adapt and validate the Parent's Evaluation of Aural/Oral Performance of Children questionnaire to Brazilian Portuguese, as well as analyzing the interaction between parents/caregivers and children. METHODS: After translated, back translated and adapted this questionnaire was administered to 13 parents or guardians of children with moderate to severe hearing loss that were treated in the ambulatory of audiology of the Institution. Parents should fill out the diary, answering the questionnaire, giving as many examples of observed behaviors for each question and return for follow-up after a week for an interview with the evaluator or child's therapist. RESULTS: Data are presented in frequency and percentage. We used chi-square test with a 5% significance level (p). Two questions were culturally adapted to Brazilian Portuguese. The questionnaires were answered by mothers most of the time (69.2%). CONCLUSIONS: The questionnaire was translated and adapted respecting the cultural aspects of the Brazilian population. It was observed that, for some questions, it is necessary care when analyzing the answers that parents provide, taking into consideration the child's age and linguistic content that is required for the observed behavior, avoiding erroneous interpretations made on the quality of amplification and the use of hearing aids or CI due to this. The questionnaire is of great importance since it measures the performance of children in their daily life situations. PMID- 27253224 TI - Addition of Anti-Angiogenetic Therapy with Bevacizumab to Chemo- and Radiotherapy for Leptomeningeal Metastases in Primary Brain Tumors. AB - Leptomeningeal dissemination of a primary brain tumor is a condition which is challenging to treat, as it often occurs in rather late disease stages in highly pretreated patients. Its prognosis is dismal and there is still no accepted standard of care. We report here a good clinical effect with a partial response in three out of nine patients and a stable disease with improvement on symptoms in two more patients following systemic anti-angiogenic treatment with bevacizumab (BEV) alone or in combination with chemo- and/or radiotherapy in a series of patients with leptomeningeal dissemination from primary brain tumors (diffuse astrocytoma WHO degrees II, anaplastic astrocytoma WHO degrees III, anaplastic oligodendroglioma WHO degrees III, primitive neuroectodermal tumor and glioblastoma, both WHO degrees IV). This translated into effective symptom control in five out of nine patients, but only moderate progression-free and overall survival times were reached. Partial responses as assessed by RANO criteria were observed in three patients (each one with anaplastic oligodendroglioma, primitive neuroectodermal tumor and glioblastoma). In these patients progression-free survival (PFS) intervals of 17, 10 and 20 weeks were achieved. In three patients (each one with diffuse astrocytoma, anaplastic astrocytoma and primitive neuroectodermal tumor) stable disease was observed with PFS of 13, 30 and 8 weeks. Another three patients (all with glioblastoma) were primary non-responders and deteriorated rapidly with PFS of 3 to 4 weeks. No severe adverse events were seen. These experiences suggest that the combination of BEV with more conventional therapy schemes with chemo- and/or radiotherapy may be a palliative treatment option for patients with leptomeningeal dissemination of brain tumors. PMID- 27253227 TI - ROC curve of the Pediatric Voice Related Quality-of-Life Survey (P-VRQOL). AB - To verify the efficiency and to determine the cutoff values that discriminate children/adolescents with and without vocal complaints, as well as the measures of sensibility, specificity and efficiency of the Brazilian Pediatric Voice Related Quality-of-Life Survey (P-VRQOL). The participants included 230 parents of children/adolescents of both genders, aged between 2 years and 18 years, with and without vocal complaints that responded the validated Brazilian version of P VRQOL. The three scores (total, physical and social-emotional) were analyzed by the Receiver Operating Characteristic Curve (ROC curve). The cutoff values, ROC curve and the measures of specificity, sensibility and efficiency varied as the score investigated - total, physical or social-emotional. The total score demonstrated excellent discrimination (efficiency=0.936; specificity=0.991; and sensibility=0.881); the social-emotional score was a reasonable indicator (efficiency=0.794; specificity=0.604; and sensibility=0.983) and the physical score was an excellent sorter (efficiency=0.918; specificity=0.946; and sensibility=0.890). The cutoff values and area under curve were: total score- cutoff=96.25 and AUC=0.98; physical score- cutoff=91.68 and AUC=0.97; social emotional score cutoff=96.87 and AUC=0.79. The P-VRQOL is an excellent sorter to discriminate children/adolescents with and without vocal complaints. The perception of parents about the presence of vocal problem allows the judge of lower quality of life in 98% of the cases, especially, in P-VRQOL physical domain. PMID- 27253229 TI - Associations Between Fish Consumption and Contaminant Biomarkers With Cardiovascular Conditions Among Older Male Anglers in Wisconsin. AB - OBJECTIVE: The aim of this study was to determine fish consumption habits and contaminant exposures associated with adverse cardiovascular outcomes among older male anglers. METHODS: One hundred fifty-four men aged 50 years and older living and fishing in Wisconsin completed a detailed survey and provided hair and blood samples. Associations between fish consumption and body burdens of several contaminants, with self-reported cardiovascular outcomes, were evaluated. RESULTS: Consuming fish species with higher methyl mercury content was positively associated with odds of angina, coronary heart disease (CHD), or heart attack, while consuming fattier species was negatively associated with high blood pressure or high cholesterol. Total mercury in blood was associated with 27% higher odds of heart attack, and certain classes of polychlorinated biphenyls were positively associated with CHD. CONCLUSION: Total mercury exposures may affect cardiovascular outcomes. Educational interventions promoting consumption of fish low in methyl mercury among older male anglers are needed. PMID- 27253228 TI - Fatigued, but Not Frail: Perceived Fatigability as a Marker of Impending Decline in Mobility-Intact Older Adults. AB - OBJECTIVES: To evaluate perceived fatigability as a predictor of meaningful functional decline in non-mobility-limited older adults. DESIGN: Longitudinal analysis of data from the Baltimore Longitudinal Study of Aging (BLSA). SETTING: National Institute on Aging, Clinical Research Unit, Baltimore, Maryland. PARTICIPANTS: Men and women aged 60 to 89 participating in the BLSA with concurrent perceived fatigability and functional assessments and follow-up functional assessment within 1 to 3 years (N = 540). MEASUREMENTS: Perceived fatigability was ascertained using the Borg rating of perceived exertion (RPE) after 5 minutes of treadmill walking at 1.5 miles per hour. Functional assessments included usual and fast gait speed, the Health, Aging and Body Composition physical performance battery (HABC PPB) and reported walking ability. Reported tiredness and energy level were examined as complementary predictors. Covariates included age, age squared, race, follow-up time, and baseline function. Meaningful decline was defined as 0.05 m/s per year for usual gait speed, 0.07 m/s per year for fast gait speed, 0.12 points/year for HABC PPB, and 1 point for walking ability index. RESULTS: Over a mean 2.1 years, 20-31% of participants declined across functional assessments. Fatigability was associated with a 13-19% greater likelihood of meaningful decline in all measures (P = .002- .02) per 1-unit RPE increase. After considering tiredness and energy level separately, findings were essentially unchanged, and neither was associated with gait speed or physical performance decline. In contrast, each separately predicted decline in reported walking ability independent of fatigability (P = .03 and P < .001, respectively). CONCLUSION: Routine assessment of fatigability may help identify older persons vulnerable to greater-than-expected functional decline. PMID- 27253230 TI - Fish Consumption, Levels of Nutrients and Contaminants, and Endocrine-Related Health Outcomes Among Older Male Anglers in Wisconsin. AB - OBJECTIVE: The aim of this study was to examine associations between endocrine disorders, fish consumption habits, and biomarkers of contaminants and nutrients METHODS: : Male anglers aged at least 50 years living in Wisconsin (n = 154) completed a questionnaire and provided biological samples. Adjusted logistic regression models were used to evaluate risk factors for endocrine outcomes. RESULTS: Nineteen percent of anglers reported either pre-diabetes or diabetes, while 4.6% reported thyroid disease. There were few associations between endocrine disease and fish consumption, fish meal source, or species, aside from a notable increase in diabetes risk with lake trout consumption. Docosahexaenoic acid, certain polychlorinated biphenyls (PCBs), and perfluorinated compounds were associated with an increased risk of diabetes or pre-diabetes. PCBs were associated with a decreased risk of thyroid disease. CONCLUSION: Fish consumption patterns may affect risk for endocrine outcomes, but direction and magnitude of association may depend on the balance of the contaminants and nutrients in the individual diet. PMID- 27253232 TI - Molecular Mechanisms of Toxicity and Cell Damage by Chemicals in a Human Pancreatic Beta Cell Line, 1.1B4. AB - OBJECTIVES: Mechanisms of toxicity and cell damage were investigated in novel clonal human pancreatic beta cell line, 1.1B4, after exposure to streptozotocin, alloxan, ninhydrin, and hydrogen peroxide. METHODS: Viability, DNA damage, insulin secretion/content, [Ca]i, and glucokinase/hexokinase, mRNA expression were measured by MTT assay, comet assay, radioimmunoassay, fluorometric imaging plate reader, enzyme-coupled photometry, and real-time polymerase chain reaction, respectively. RESULTS: Chemicals significantly reduced 1.1B4 cell viability in a time/concentration-dependent manner. Chronic 18-hour exposure decreased cellular insulin, glucokinase, and hexokinase activities. Chemicals decreased transcription of INS, GCK, PCSK1, PCSK2, and GJA1 (involved in secretory function). Insulin release and [Ca]i responses to nutrients and membrane depolarizing agents were impaired. Streptozotocin and alloxan up-regulated transcription of genes, SOD1 and SOD2 (antioxidant enzymes). Ninhydrin and hydrogen peroxide up-regulated SOD2 transcription, whereas alloxan and hydrogen peroxide increased CAT transcription. Chemicals induced DNA damage, apoptosis, and increased caspase 3/7 activity. Streptozotocin and alloxan decreased transcription of BCL2 while increasing transcription of BAX. Chemicals did not affect transcription of HSPA4 and HSPA5 and nitrite production. CONCLUSIONS: 1.1B4 cells represent a useful model of human beta cells. Chemicals impaired 1.1B4 cell secretory function and activated antioxidant defense and apoptotic pathways without activating endoplasmic reticulum stress response/nitrosative stress. PMID- 27253231 TI - A Randomized Comparative Study of 24- and 6-Hour Infusion of Nafamostat Mesilate for the Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Prospective Randomized Comparison Trial. AB - OBJECTIVES: Although prolonged intravenous infusion (24 hours) of nafamostat mesilate is effective for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, it requires hospitalization and is expensive. The aim of this study was to compare the efficacy of 24- versus 6-hour intravenous infusion of 20 mg nafamostat mesilate for the prevention of post-ERCP pancreatitis (PEP). METHODS: A total of 382 patients who underwent ERCP were randomly assigned into 2 groups: 24 hours or 6 hours. In both groups, nafamostat mesilate (20 mg) infusion was initiated up to an hour before ERCP and continued for either 24 or 6 hours. RESULTS: The overall incidence of pancreatitis was 2.4% (9/371). The rates of PEP following 24- and 6-hour infusion were 2.8% (5/179) and 2.1% (4/192), respectively (P = 0.744). No significant difference was observed in the severity of pancreatitis between the groups. On multivariate analysis, increasing pancreatic duct cannulations (odds ratio, 1.685; 95% confidence interval, 1.036-2.741; P = 0.036) was identified as a statistically significant risk factor of PEP. CONCLUSIONS: No difference was found in the incidence of PEP regardless of the duration of nafamostat mesilate infusion. Therefore, 6-hour infusion of 20 mg nafamostat mesilate may be useful for the prevention of PEP in an outpatient setting. PMID- 27253233 TI - Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls. AB - OBJECTIVE: This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. METHODS: The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. RESULTS: Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P < 0.01). The difference in smoking frequency was not significant between the patients with idiopathic pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. CONCLUSIONS: Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis. PMID- 27253234 TI - Assessment of D-Dimers for the Early Prediction of Complications in Acute Pancreatitis. AB - OBJECTIVES: Severe acute pancreatitis (AP) is characterized by early microcirculation defects causing hypercoagulability. The purpose of this study was to evaluate the early predictive value of D-dimers in complicated AP. METHODS: This was a prospective single-center study conducted between September 2010 and April 2012. All patients had AP for less than 48 hours duration at admission. The plasma D-dimer level was determined at admission and every 12 hours over 3 days and compared to other validated severity criteria. RESULTS: Of 71 patients admitted with AP, 36 (53.1%) developed complicated AP. A threshold D dimer level greater than 1474 ng/mL at 48 hours after pain onset was predictive of complications with an area under the curve (AUC) of 0.76. Combining D-dimers and C-reactive protein levels at 48 hours increased the prediction of complications (AUC of 0.83). At 36 hours, D-dimers greater than 1474 ng/mL predicted the occurrence of complications with an AUC of 0.75. CONCLUSIONS: D Dimer levels were predictive of complications of AP as early as 36 hours after the onset of pain. This simple and reproducible marker might be useful in clinical practice to improve the early management of complicated AP. PMID- 27253235 TI - Endocrine prevention of chemotherapy-induced ovarian failure. AB - PURPOSE OF REVIEW: Fertility preservation has recently gained a worldwide interest among fertility specialists, oncologists, and all healthcare providers. Thus, the protection against iatrogenic infertility caused by chemotherapy assumes a high priority. Specifically, the issue of endocrine prevention of gonadotoxicity is still a controversial subject. RECENT FINDINGS: During the last year, many publications on this subject appeared, swinging the pendulum toward the beneficial role of gonadotropin-releasing hormone agonist (GnRHa) cotreatment for fertility preservation despite gonadotoxic chemotherapy. Here, we summarize the recent publications on fertility preservation and minimizing chemotherapy induced gonadotoxicity. SUMMARY: More than 10 recent meta-analyses have concluded that GnRHa is beneficial and may decrease the risk of premature ovarian failure and increase the pregnancy rate in survivors. Furthermore, two recent international meetings of experts have concluded that GnRHa is effective and should be offered to every young woman facing gonadotoxic chemotherapy. PMID- 27253236 TI - Updates in uterine fibroid tissue extraction. AB - PURPOSE OF REVIEW: Safety concerns regarding morcellation of presumed benign fibroid disease have led to an increase in recent research activity on this topic, as well as advances in surgical technique. RECENT FINDINGS: The prevalence of occult leiomyosarcoma is debated; however, estimates from a robust meta analysis suggest it may be in the range of 1 case per 1960-8300 fibroid surgeries. Advancing age is an important clinical risk factor for occult malignancy. The impact of tumor morcellation may vary by mode of tissue removal, though tissue fragmentation is consistently associated with poorer outcomes. Decision and cost analyses continue to support laparoscopic hysterectomy as a low morbidity and cost-effective approach. The increased scrutiny on fibroid procedures in the past few years may lead to changes in surgical approach; however, alternative tissue extraction options are evolving, including incorporation of contained morcellation. SUMMARY: Although the incidence of occult leiomyosarcoma is low, outcomes are poor and may be worsened by morcellation. By addressing risk factors for malignancy and incorporating evolving surgical techniques into practice, gynecologists can continue to offer patients a minimally invasive approach for fibroid management. PMID- 27253237 TI - Endometrial ablation: considerations and complications. AB - PURPOSE OF REVIEW: The purpose of the review is to update the reader on endometrial ablation as a treatment for abnormal uterine bleeding, including modifications to initial treatment guidelines and current data on long-term outcomes. RECENT FINDINGS: Endometrial ablation continues to be a successful treatment for abnormal uterine bleeding, with new indications potentially forthcoming. Patient selection is key, as certain patient groups are at increased risk for ablation failure and complications. SUMMARY: Gynecologists should continue to offer this treatment to appropriate patients with abnormal uterine bleeding, with adequate counseling regarding anticipated success rates, factors associated with failure, alternative treatments, and long-term consequences related to ablation. PMID- 27253238 TI - Management considerations for patients with uterine fibroids and concurrent venous thromboembolism. AB - PURPOSE OF REVIEW: The purpose is to provide an update on management strategies for uterine fibroids in the setting of venous thromboembolism (VTE). RECENT FINDINGS: Uterine fibroids and VTE are independently associated with morbidity and increasing healthcare costs. Women with large uterine fibroids have a higher likelihood of VTE. Current strategies for stratifying patients with VTE take into account the nature of the VTE (i.e., truly provoked or unprovoked) and many patients may only require short-term anticoagulation. In those patients with risk factors for recurrent VTE, longer term anticoagulation may be required. SUMMARY: In women with large uterine fibroids, the likelihood of concurrent VTE increases. Peri and postoperative management should be determined based on patient-specific risk stratification, with the majority of patients requiring short-term anticoagulation. Further risk stratification may be required for patients with essentially an unprovoked VTE, and consultation with a thrombosis specialist is recommended. PMID- 27253239 TI - Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis patients: a Bayesian mixed treatment comparison. AB - BACKGROUND/AIMS: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to 'traditional' disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). METHODS: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, lef lunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, inf liximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). RESULTS: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. CONCLUSIONS: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients. PMID- 27253240 TI - Paving the way for new agents; is standard chemotherapy part of the treatment paradigm for chronic lymphocytic leukemia in the future? AB - INTRODUCTION: First and second generation tyrosine kinase inhibitors, represent a new, fully biologic and targeted approach to chronic lymphocytic leukemia and allowed to obtain high responses and acceptable tolerability even in elderly and high risk patients. On the other hand, prolonged experience with these agents has raised some questions on unexpected toxicities, response quality, treatment duration and onset of resistances. AREAS COVERED: This review analyzes the main published studies with the aim to discuss whether, in future, new agents could become a part of standard treatments or even replace the chemo-immunotherapy in chronic lymphocytic leukemia. Expert commentary: Despite different trials has been already published and many are still ongoing, follow up times are, at present, too short. A chemo-free approach surely represents a desirable goal for chronic lymphocytic leukemia, nevertheless longer observation is warranted to better define the correct use of targeted therapies. PMID- 27253261 TI - Ecocultural patterns of family engagement among low-income Latino families of preschool children. AB - For the 5 million low-income Latino children in the United States who are disproportionately impacted by the numerous risk factors associated with poverty, it is essential to identify proximal protective factors that mitigate these risks and bolster the academic and social skills that are foundational to a successful transition into formal schooling. Using ecocultural theory as a lens to guide this work, the present study: (a) described patterns of culture-contextualized family engagement among a low-income, Latino sample, and (b) examined relations between these patterns, family demographic factors, and children's language and social skills in preschool. Across Spanish and English language subsamples, we found evidence that there is heterogeneity in patterns of family engagement within and across language groups, such that different forms of family engagement defined the high engagement profiles in particular. We also found that demographic factors (such as child gender, family structure, and parental education and employment) predicted these patterns differentially across language groups, and that these patterns related to children's social and language skills in meaningful ways. Findings provide directions for future research, theory, and practice with this heterogeneous cultural group. (PsycINFO Database Record PMID- 27253263 TI - Productive extension of semantic memory in school-aged children: Relations with reading comprehension and deployment of cognitive resources. AB - We investigated 7- to 10-year-old children's productive extension of semantic memory through self-generation of new factual knowledge derived through integration of separate yet related facts learned through instruction or through reading. In Experiment 1, an experimenter read the to-be-integrated facts. Children successfully learned and integrated the information and used it to further extend their semantic knowledge, as evidenced by high levels of correct responses in open-ended and forced-choice testing. In Experiment 2, on half of the trials, the to-be-integrated facts were read by an experimenter (as in Experiment 1) and on half of the trials, children read the facts themselves. Self generation performance was high in both conditions (experimenter- and self-read); in both conditions, self-generation of new semantic knowledge was related to an independent measure of children's reading comprehension. In Experiment 3, the way children deployed cognitive resources during reading was predictive of their subsequent recall of newly learned information derived through integration. These findings indicate self-generation of new semantic knowledge through integration in school-age children as well as relations between this productive means of extension of semantic memory and cognitive processes engaged during reading. (PsycINFO Database Record PMID- 27253262 TI - Ecodevelopmental trajectories of family functioning: Links with HIV/STI risk behaviors and STI among Black adolescents. AB - We examined the effects of family functioning trajectories on sexual risk behaviors and STI in adolescents. A sample of 850 predominantly (80%) Black adolescents from Michigan, United States, was assessed at baseline, 12, 24, and 36 months postbaseline. Adolescents were from working-class families with a mean age of 14.9 years (SD = .64, Range = 13.9 to 16.9) at baseline. Participants completed measures of family functioning at each time point. At 36 months postbaseline, levels of sexual risk behaviors, including sex initiation, unprotected sex, and alcohol or drug use before last sexual intercourse, and STIs were assessed. Latent class growth analysis (LCGA) yielded 4-class solutions for family conflict and parent support. Adolescents with high or increasing family conflict trajectories, and low or decreasing family support trajectories, were at relatively greater risk of sexual risk behaviors and STIs. Yet, the additional trajectories differ across outcomes highlighting the complexities of the role of family functioning on sexual risk behaviors and STIs over time. Multiple Group LCGA indicate some findings vary as a function of gender. (PsycINFO Database Record PMID- 27253264 TI - Personal and familial predictors of peer victimization trajectories from primary to secondary school. AB - Using a sample of 767 children (403 girls, 364 boys), this study aimed to (a) identify groups with distinct trajectories of peer victimization over a 6-year period from primary school through the transition to secondary school, and (b) examine the associated personal (i.e., aggression or internalizing problems) and familial (family status, socioeconomic status, the parent-child relationship) predictors. Peer victimization was assessed via self-reports from Grades 4 through 9 (ages 10 through 15 years), aggression and internalizing problems were assessed in Grade 4 via peer nominations, and the parent-child relationship was assessed in Grade 7 (i.e., right after the transition to secondary school) via parent-reports. Growth Mixture modeling revealed 1 group (62%) who experienced little victimization in primary school and even less in secondary school, another group (31%) who was victimized in primary but not or much less in secondary school, and a third group (7%) who was chronically victimized in both school contexts. Boys were more likely than girls to follow any elevated victimization trajectory. Chronic victimization across primary and secondary school was predicted by nonintact family status and a combination of both internalizing problems and aggression compared with nonvictimized youth. In contrast, transitory victimization during primary but not in secondary school was predicted by aggression, but not internalizing problems. Support as well as conflict in the parent-child relationship also showed significant, albeit distinct associations with the different peer victimization trajectories. (PsycINFO Database Record PMID- 27253265 TI - Environmental impacts of genetically modified (GM) crop use 1996-2014: Impacts on pesticide use and carbon emissions. AB - This paper updates previous assessments of important environmental impacts associated with using crop biotechnology in global agriculture. It focuses on the environmental impacts associated with changes in pesticide use and greenhouse gas emissions arising from the use of GM crops since their first widespread commercial use in the mid 1990s. The adoption of GM insect resistant and herbicide tolerant technology has reduced pesticide spraying by 581.4 million kg (-8.2%) and, as a result, decreased the environmental impact associated with herbicide and insecticide use on these crops (as measured by the indicator, the Environmental Impact Quotient [EIQ]) by18.5%. The technology has also facilitated important cuts in fuel use and tillage changes, resulting in a significant reduction in the release of greenhouse gas emissions from the GM cropping area. In 2014, this was equivalent to removing nearly 10 million cars from the roads. PMID- 27253266 TI - Necessity - the Mother of Invention. PMID- 27253270 TI - Nanotwinned Boron Suboxide (B6O): New Ground State of B6O. AB - Nanotwinned structures in superhard ceramics rhombohedral boron suboxide (R-B6O) have been examined using a combination of transmission electron microscopy (TEM) and quantum mechanics (QM). QM predicts negative relative energies to R-B6O for various twinned R-B6O (denoted as tau-B6O, 2tau-B6O, and 4tau-B6O), consistent with the recently predicted B6O structure with Cmcm space group (tau-B6O) which has an energy 1.1 meV/B6O lower than R-B6O. We report here TEM observations of this tau-B6O structure, confirming the QM predictions. QM studies under pure shear deformation and indentation conditions are used to determine the deformation mechanisms of the new tau-B6O phase which are compared to R-B6O and 2tau-B6O. The lowest stress slip system of tau-B6O is (010)/?001? which transforms tau-B6O to R-B6O under pure shear deformation. However, under indentation conditions, the lowest stress slip system changes to (001)/?110?, leading to icosahedra disintegration and hence amorphous band formation. PMID- 27253269 TI - Are the Physical Activity Parenting Practices Reported by US and Canadian Parents Captured in Currently Published Instruments? AB - BACKGROUND: The purpose of this study was to compare the physical activity parenting practices (PAPPs) parents report using with the PAPPs incorporated in the published literature. METHODS: PAPPs in the literature were identified by reviewing the content of 74 published PAPP measures obtained from current systematic reviews supplemented with a literature search. The types of PAPPs used by parents were identified by surveying a stratified sample of 134 Canadian and US parents of 5- to 12 year-old children. Items from the literature and parent responses were coded using the same coding scheme. Differences between the PAPPs emphasized by the parents and the literature were examined. RESULTS: Parents significantly emphasized different issues than what is measured in the literature (P < .001). Parents emphasized more control (13.6% vs. 6.9%), modeling and teaching (13.2% vs. 9.2%), and structural strategies (32.2% vs. 28.6%) and less autonomy support (11.8% vs. 14.0%), logistical support (9.9% vs. 12.8%), and responsiveness strategies (19.3% vs. 28.5%). CONCLUSIONS: Physical activity practices most often employed by parents are not the ones emphasized in current measures. The extent to which putting more emphasis on the areas identified by parents will increase the predictive validity of the measures warrants further examination. PMID- 27253267 TI - Oxidative stress during early pregnancy and birth outcomes. AB - OBJECTIVE: Routine high-dose Fe supplementation in non-anaemic pregnant women may induce oxidative stress and eventually affect birth outcomes. The aim of the present study was to measure oxidative stress markers in pregnant women with low/normal and high Hb values in trimester 1 (Hb1) and to relate these to birth weight. DESIGN: A cross-sectional study where selected oxidative stress markers were analysed in both maternal (trimester 1; T1) and cord blood samples and correlated with birth weight. SETTING: A tertiary hospital in urban South India. SUBJECTS: One hundred women were chosen based on their Hb1 values (forty women with low/normal Hb1 (<110 g/l) and sixty women with high Hb1 (>=120 g/l)). RESULTS: In T1, women with high Hb1 values were found to have lower paraoxonase-1 (PON-1) activity (424.7 (sd 163.7) v. 532.9 (sd 144.7) pmol p-nitrophenol formed/min per ml plasma, P=0.002) and higher lipid peroxides compared with women with low/normal Hb1. Routine supplementation of Fe to these women resulted in persistent lower PON-1 activity in cord blood (P=0.02) and directionally lower (P=0.142) birth weights. Furthermore, women with high Hb1 who delivered low-birth weight babies were observed to have lowest PON-1 activity in T1. No changes were observed in other markers (myeloperoxidase activity and total antioxidant levels). CONCLUSIONS: Routine Fe supplementation in pregnant women with high Hb1 associated with increased oxidative stress, as reflected by low PON-1 activity in T1, could potentially lead to deleterious effects on birth weight. PMID- 27253271 TI - Toward Efficient Thick Active PTB7 Photovoltaic Layers Using Diphenyl Ether as a Solvent Additive. AB - The development of thick organic photovoltaics (OPV) could increase absorption in the active layer and ease manufacturing constraints in large-scale solar panel production. However, the efficiencies of most low-bandgap OPVs decrease substantially when the active layers exceed ~100 nm in thickness (because of low crystallinity and a short exciton diffusion length). Herein, we report the use of solvent additive diphenyl ether (DPE) that facilitates the fabrication of thick (180 nm) active layers and triples the power conversion efficiency (PCE) of conventional thienothiophene-co-benzodithiophene polymer (PTB7)-based OPVs from 1.75 to 6.19%. These results demonstrate a PCE 20% higher than those of conventional (PTB7)-based OPV devices using 1,8-diiodooctane. Morphology studies reveal that DPE promotes the formation of nanofibrillar networks and ordered packing of PTB7 in the active layer that facilitate charge transport over longer distances. We further demonstrate that DPE improves the fill factor and photocurrent collection by enhancing the overall optical absorption, reducing the series resistance, and suppressing bimolecular recombination. PMID- 27253268 TI - Adoption of Splenic Enhancement to Time and Trigger the Late Hepatic Arterial Phase During MDCT of the Liver: Proof of Concept and Clinical Feasibility. AB - OBJECTIVE: The purpose of this study was to prospectively investigate the clinical feasibility of adopting splenic enhancement for timing and triggering the acquisition of late hepatic arterial phase images during multiphasic liver MDCT for assessment of hypervascular tumors. SUBJECTS AND METHODS: Forty-eight patients (33 men, 15 women; median age, 59 years; chronic liver disease, 23 patients; portal venous hypertension, 17 patients) with a total of 81 hypervascular liver tumors underwent liver MDCT by random assignment to one of two scanning protocols. Scanning delay for the late hepatic arterial phase was determined by assessment of time-to-peak splenic enhancement (splenic-triggering protocol) or aortic enhancement (aortic-triggering protocol). Acquisition timing, vascular attenuation, liver attenuation and homogeneity, signal-to-noise ratio, tumor-to-liver contrast, and tumor-to-liver contrast-to-noise ratio were compared. Two blinded independent observers used Likert scales to score timing adequacy (3-point scale), diagnostic confidence (5-point scale), and per lesion conspicuity (4-point scale) for hypervascular tumor detection. RESULTS: The splenic- and aortic-triggering protocols had significant differences in mean late hepatic arterial phase imaging timing (splenic, 36 +/- 6 seconds; aortic, 32 +/- 3 seconds; p = 0.010). Images obtained with the splenic-triggering protocol had significantly better observer-based judgment of adequacy (splenic, 2.04; aortic, 1.58; p = 0.002). Mean attenuation and signal-to-noise ratios from liver and portal vein were significantly higher with the splenic- than with the aortic triggering protocol (p < 0.0001). The splenic-triggering protocol was associated with significant improvement in homogeneity of liver attenuation (p < 0.0001). Although the splenic-triggering protocol was associated with significantly higher lesion conspicuity than was the aortic-triggering protocol (p = 0.022), there was no significant difference in tumor detection rate. CONCLUSION: Our results provide a clinical foundation for and proof of principle that the adoption of splenic enhancement renders an optimal temporal window for late hepatic arterial phase imaging during MDCT of the liver for assessment of hypervascular tumors. PMID- 27253272 TI - The early developments of preeclampsia drugs. PMID- 27253321 TI - 3p14p12 deletion syndrome: report of a new case providing further evidence of a clinically recognizable syndrome. PMID- 27253320 TI - Highly Repeatable Dissolution Dynamic Nuclear Polarization for Heteronuclear NMR Metabolomics. AB - At natural (13)C abundance, metabolomics based on heteronuclear NMR is limited by sensitivity. We have recently demonstrated how hyperpolarization by dissolution dynamic nuclear polarization (D-DNP) assisted by cross-polarization (CP) provides a reliable way of enhancing the sensitivity of heteronuclear NMR in dilute mixtures of metabolites. In this Technical Note, we evaluate the precision of this experimental approach, a critical point for applications to metabolomics. The higher the repeatability, the greater the likelihood that one can detect small biologically relevant differences between samples. The average repeatability of our state-of-the-art D-DNP NMR equipment for samples of metabolomic relevance (20 mg dry weight tomato extracts) is 3.6% for signals above the limit of quantification (LOQ) and 6.4% when all the signals above the limit of detection (LOD) are taken into account. This first report on the repeatability of D-DNP highlights the compatibility of the technique with the requirements of metabolomics and confirms its potential as an analytical tool for such applications. PMID- 27253322 TI - Interfacial rheometry of polymer at a water-oil interface by intra-pair magnetophoresis. AB - We describe an interfacial rheometry technique based on pairs of micrometer-sized magnetic particles at a fluid-fluid interface. The particles are repeatedly attracted and repelled by well-controlled magnetic dipole-dipole forces, so called interfacial rheometry by intra-pair magnetophoresis (IPM). From the forces (~pN), displacements (~MUm) and velocities (~MUm s(-1)) of the particles we are able to quantify the interfacial drag coefficient of particles within a few seconds and over very long timescales. The use of local dipole-dipole forces makes the system insensitive to fluid flow and suited for simultaneously recording many particles in parallel over a long period of time. We apply IPM to study the time-dependent adsorption of an oil-soluble amino-modified silicone polymer at a water-oil interface using carboxylated magnetic particles. At low polymer concentration the carboxylated particles remain on the water side of the water-oil interface, while at high polymer concentrations the particles transit into the oil phase. Both conditions show a drag coefficient that does not depend on time. However, at intermediate polymer concentrations data show an increase of the interfacial drag coefficient as a function of time, with an increase over more than three orders of magnitude (10(-7) to 10(-4) N s m(-1)), pointing to a strong polymer-polymer interaction at the interface. The time-dependence of the interfacial drag appears to be highly sensitive to the polymer concentration and to the ionic strength of the aqueous phase. We foresee that IPM will be a very convenient technique to study fluid-fluid interfaces for a broad range of materials systems. PMID- 27253319 TI - Self-stigma, personality traits, and willingness to seek treatment in a community sample. AB - Stigma has received attention as a major barrier toward effective mental health service delivery, and previous research has demonstrated that the Five-Factor Model (FFM) domain of Openness to Experience is negatively correlated with stigmatized views of mental health. However, a lack of established relationships between personality and self-stigma, as well as how these concepts affect an individual's treatment-seeking intentions, has left a gap in the literature. To address this, our study recruited a low-income community sample and tested (a) the relationship between self-stigma of mental health treatment and the FFM, (b) the relationship between self-stigma and treatment-seeking intentions, and (c) the incremental validity of FFM personality beyond stigma in the prediction of treatment seeking. Results suggest that there is some incongruence with previous research on personality's relationship to stigma, personality does not act as an additive component in the prediction of the relationship between stigma and treatment seeking, and stigma is related only to the perceived need for mental health treatment but not to an individual's openness to seek that treatment. The discussion concludes with implications for the contextualization and treatment of stigma as a barrier for mental health treatment and a general synthesis of the personality trait profiles for those holding stigmatizing views of mental health. (PsycINFO Database Record PMID- 27253325 TI - Effects of Addition of Linseed and Marine Algae to the Diet on Adipose Tissue Development, Fatty Acid Profile, Lipogenic Gene Expression, and Meat Quality in Lambs. AB - This study examined the effect of linseed and algae on growth and carcass parameters, adipocyte cellularity, fatty acid profile and meat quality and gene expression in subcutaneous and intramuscular adipose tissues (AT) in lambs. After weaning, 33 lambs were fed three diets up to 26.7 +/- 0.3 kg: Control diet (barley and soybean); L diet (barley, soybean and 10% linseed) and L-A diet (barley, soybean, 5% linseed and 3.89% algae). Lambs fed L-A diet showed lower average daily gain and greater slaughter age compared to Control and L (P < 0.001). Carcass traits were not affected by L and L-A diets, but a trend towards greater adipocyte diameter was observed in L and L-A in the subcutaneous AT (P = 0.057). Adding either linseed or linseed and algae increased alpha-linolenic acid and eicosapentaenoic acid contents in both AT (P < 0.001); however, docosahexaenoic acid was increased by L-A (P < 0.001). The n-6/n-3 ratio decreased in L and L-A (P < 0.001). Algae had adverse effects on meat quality, with greater lipid oxidation and reduced ratings for odor and flavor. The expression of lipogenic genes was downregulated in the subcutaneous AT (P < 0.05): acetyl-CoA carboxylase 1 (ACACA) in L and L-A and lipoprotein lipase (LPL) and stearoyl-CoA desaturase (SCD) in L-A. Fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2) and fatty acid elongase 5 (ELOVL5) were unaffected. In the subcutaneous AT, supplementing either L or L-A increased peroxisome proliferator-activated receptor gamma (PPARG) and CAAT-enhancer binding protein alpha (CEBPA) (P < 0.05), although it had no effect on sterol regulatory element binding factor 1 (SREBF1). In the intramuscular AT, expression of ACACA, SCD, FADS1 and FADS2 decreased in L and L-A (P < 0.001) and LPL in L (P < 0.01), but PPARG, CEBPA and SREBF1 were unaffected. PMID- 27253324 TI - Modeling and Re-Engineering of Azotobacter vinelandii Alginate Lyase to Enhance Its Catalytic Efficiency for Accelerating Biofilm Degradation. AB - Alginate is known to prevent elimination of Pseudomonas aeruginosa biofilms. Alginate lyase (AlgL) might therefore facilitate treatment of Pseudomonas aeruginosa-infected cystic fibrosis patients. However, the catalytic activity of wild-type AlgL is not sufficiently high. Therefore, molecular modeling and site directed mutagenesis of AlgL might assist in enzyme engineering for therapeutic development. AlgL, isolated from Azotobacter vinelandii, catalyzes depolymerization of alginate via a beta-elimination reaction. AlgL was modeled based on the crystal structure template of Sphingomonas AlgL species A1-III. Based on this computational analysis, AlgL was subjected to site-directed mutagenesis to improve its catalytic activity. The kcat/Km of the K194E mutant showed a nearly 5-fold increase against the acetylated alginate substrate, as compared to the wild-type. Double and triple mutants (K194E/K245D, K245D/K319A, K194E/K245D/E312D, and K194E/K245D/K319A) were also prepared. The most potent mutant was observed to be K194E/K245D/K319A, which has a 10-fold improved kcat value (against acetylated alginate) compared to the wild-type enzyme. The antibiofilm effect of both AlgL forms was identified in combination with piperacillin/tazobactam (PT) and the disruption effect was significantly higher in mutant AlgL combined with PT than wild-type AlgL. However, for both the wild type and K194E/K245D/K319A mutant, the use of the AlgL enzyme alone did not show significant antibiofilm effect. PMID- 27253323 TI - Small RNA-Based Antiviral Defense in the Phytopathogenic Fungus Colletotrichum higginsianum. AB - Even though the fungal kingdom contains more than 3 million species, little is known about the biological roles of RNA silencing in fungi. The Colletotrichum genus comprises fungal species that are pathogenic for a wide range of crop species worldwide. To investigate the role of RNA silencing in the ascomycete fungus Colletotrichum higginsianum, knock-out mutants affecting genes for three RNA-dependent RNA polymerase (RDR), two Dicer-like (DCL), and two Argonaute (AGO) proteins were generated by targeted gene replacement. No effects were observed on vegetative growth for any mutant strain when grown on complex or minimal media. However, Deltadcl1, Deltadcl1Deltadcl2 double mutant, and Deltaago1 strains showed severe defects in conidiation and conidia morphology. Total RNA transcripts and small RNA populations were analyzed in parental and mutant strains. The greatest effects on both RNA populations was observed in the Deltadcl1, Deltadcl1Deltadcl2, and Deltaago1 strains, in which a previously uncharacterized dsRNA mycovirus [termed Colletotrichum higginsianum non-segmented dsRNA virus 1 (ChNRV1)] was derepressed. Phylogenetic analyses clearly showed a close relationship between ChNRV1 and members of the segmented Partitiviridae family, despite the non-segmented nature of the genome. Immunoprecipitation of small RNAs associated with AGO1 showed abundant loading of 5'U-containing viral siRNA. C. higginsianum parental and Deltadcl1 mutant strains cured of ChNRV1 revealed that the conidiation and spore morphology defects were primarily caused by ChNRV1. Based on these results, RNA silencing involving ChDCL1 and ChAGO1 in C. higginsianum is proposed to function as an antiviral mechanism. PMID- 27253326 TI - Second Language Ability and Emotional Prosody Perception. AB - The present study examines the effect of language experience on vocal emotion perception in a second language. Native speakers of French with varying levels of self-reported English ability were asked to identify emotions from vocal expressions produced by American actors in a forced-choice task, and to rate their pleasantness, power, alertness and intensity on continuous scales. Stimuli included emotionally expressive English speech (emotional prosody) and non linguistic vocalizations (affect bursts), and a baseline condition with Swiss French pseudo-speech. Results revealed effects of English ability on the recognition of emotions in English speech but not in non-linguistic vocalizations. Specifically, higher English ability was associated with less accurate identification of positive emotions, but not with the interpretation of negative emotions. Moreover, higher English ability was associated with lower ratings of pleasantness and power, again only for emotional prosody. This suggests that second language skills may sometimes interfere with emotion recognition from speech prosody, particularly for positive emotions. PMID- 27253328 TI - Effect of dolomite decomposition under CO2 on its multicycle CO2 capture behaviour under calcium looping conditions. AB - One of the major drawbacks that hinder the industrial competitiveness of the calcium looping (CaL) process for CO2 capture is the high temperature (~930-950 degrees C) needed in practice to attain full calcination of limestone in a high CO2 partial pressure environment for short residence times as required. In this work, the multicycle CO2 capture performance of dolomite and limestone is analysed under realistic CaL conditions and using a reduced calcination temperature of 900 degrees C, which would serve to mitigate the energy penalty caused by integration of the CaL process into fossil fuel fired power plants. The results show that the fundamental mechanism of dolomite decomposition under CO2 has a major influence on its superior performance compared to limestone. The inert MgO grains resulting from dolomite decomposition help preserve a nanocrystalline CaO structure wherein carbonation in the solid-state diffusion controlled phase is promoted. The major role played by the dolomite decomposition mechanism under CO2 is clearly demonstrated by the multicycle CaO conversion behaviour observed for samples decomposed at different preheating rates. Limestone decomposition at slow heating rates yields a highly crystalline and poorly reactive CaCO3 structure that requires long periods to fully decarbonate and shows a severely reduced capture capacity in subsequent cycles. On the other hand, the nascent CaCO3 produced after dolomite half-decomposition consists of nanosized crystals with a fast decarbonation kinetics regardless of the preheating rate, thus fully decomposing from the very first cycle at a reduced calcination temperature into a CaO skeleton with enhanced reactivity as compared to limestone derived CaO. PMID- 27253327 TI - Evaluating Crop Area Mapping from MODIS Time-Series as an Assessment Tool for Zimbabwe's "Fast Track Land Reform Programme". AB - Moderate Resolution Imaging Spectroradiometer (MODIS) data forms the basis for numerous land use and land cover (LULC) mapping and analysis frameworks at regional scale. Compared to other satellite sensors, the spatial, temporal and spectral specifications of MODIS are considered as highly suitable for LULC classifications which support many different aspects of social, environmental and developmental research. The LULC mapping of this study was carried out in the context of the development of an evaluation approach for Zimbabwe's land reform program. Within the discourse about the success of this program, a lack of spatially explicit methods to produce objective data, such as on the extent of agricultural area, is apparent. We therefore assessed the suitability of moderate spatial and high temporal resolution imagery and phenological parameters to retrieve regional figures about the extent of cropland area in former freehold tenure in a series of 13 years from 2001-2013. Time-series data was processed with TIMESAT and was stratified according to agro-ecological potential zoning of Zimbabwe. Random Forest (RF) classifications were used to produce annual binary crop/non crop maps which were evaluated with high spatial resolution data from other satellite sensors. We assessed the cropland products in former freehold tenure in terms of classification accuracy, inter-annual comparability and heterogeneity. Although general LULC patterns were depicted in classification results and an overall accuracy of over 80% was achieved, user accuracies for rainfed agriculture were limited to below 65%. We conclude that phenological analysis has to be treated with caution when rainfed agriculture and grassland in semi-humid tropical regions have to be separated based on MODIS spectral data and phenological parameters. Because classification results significantly underestimate redistributed commercial farmland in Zimbabwe, we argue that the method cannot be used to produce spatial information on land-use which could be linked to tenure change. Hence capabilities of moderate resolution data are limited to assess Zimbabwe's land reform. To make use of the unquestionable potential of MODIS time-series analysis, we propose an analysis of plant productivity which allows to link annual growth and production of vegetation to ownership after Zimbabwe's land reform. PMID- 27253330 TI - Development of Membrane-Based Desiccant Fiber for Vacuum Desiccant Cooling. AB - A novel hydrophobic membrane-based desiccant fiber (MDF) was developed by loading lithium chloride into hydrophobic hollow fiber membranes. The MDF thus made was then tested for vapor absorption under controlled conditions. Furthermore, an MDF pad, which was made by weaving MDF into a piece of garment, was built into a laboratory vacuum desiccant cooling (VDC) setup, which included the MDF pad as the desiccant layer and a cooling towel saturated with water as the water reservoir, to test the cooling effects at atmospheric pressure and vacuum of 25 in. of Hg. Results indicate that MDF is suitable for applications such as in VDC. Mass and heat transfer of vapor absorption by MDF were also analyzed. PMID- 27253332 TI - Development and Validation of the Sexual Contingent Self-Worth Scale. AB - Sexual contingent self-worth (CSW) refers to self-worth that is dependent on maintaining a sexual relationship, and has not been studied previously. This novel construct may have implications for sexual, relationship, and psychological well-being, because it could affect the cognitions, affect, and behaviors of individuals in sexual relationships. The purpose of this study was to develop the Sexual Contingent Self-Worth Scale and examine its reliability and validity in community samples. Two separate online studies (N = 329 and N = 282) included men and women who were in committed, sexually active relationships. The Sexual CSW Scale was adapted from a validated measure of relationship CSW. In Study 1, participants completed the Sexual CSW Scale, whereas in Study 2, participants also responded to standardized measures of related constructs. In addition, participants completed the Sexual CSW Scale again two weeks later in Study 2. Factor analysis yielded two subscales: (a) sexual CSW dependent on positive sexual events in the relationship and (b) sexual CSW dependent on negative sexual events. Results indicated good construct validity, incremental validity, internal consistency, and test-retest reliability for the Sexual CSW Scale. This research contributes to the fields of both CSW and sexuality by introducing a novel domain of CSW. PMID- 27253331 TI - Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of ovarian cancer. Many studies have evaluated these approaches, but the results were too inconsistent to be conclusive. This study is the first to systematically evaluate the accuracy of circulating cfDNA for the diagnosis of ovarian cancer by conducting meta analysis. METHODS: We searched PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure (CNKI) databases systematically for relevant literatures up to December 10, 2015. All analyses were conducted using Meta DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of circulating cfDNA for the diagnosis of ovarian cancer were pooled. Meta-regression was performed to identify the sources of heterogeneity. RESULTS: This meta-analysis included a total of 9 studies, including 462 ovarian cancer patients and 407 controls. The summary estimates for quantitative analysis of circulating cfDNA in ovarian cancer screen were as follows: sensitivity, 0.70 (95% confidence interval (CI), 0.65-0.74); specificity, 0.90 (95% CI, 0.87-0.93); positive likelihood ratio, 6.60 (95% CI, 3.90-11.17); negative likelihood ratio, 0.34 (95% CI, 0.25-0.47); diagnostic odds ratio, 26.05 (95% CI, 14.67-46.26); and area under the curve, 0.89 (95% CI, 0.83-0.95), respectively. There was no statistical significance for the evaluation of publication bias. CONCLUSIONS: Current evidence suggests that quantitative analysis of cfDNA has unsatisfactory sensitivity but acceptable specificity for the diagnosis of ovarian cancer. Further large-scale prospective studies are required to validate the potential applicability of using circulating cfDNA alone or in combination with conventional markers as diagnostic biomarker for ovarian cancer and explore potential factors that may influence the accuracy of ovarian cancer diagnosis. PMID- 27253329 TI - Non-degradative Ubiquitination of Protein Kinases. AB - Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP 70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well. PMID- 27253333 TI - Embodiment and aging in contemporary physiotherapy. AB - Contemporary discourses in the health sciences vary in their treatment of aging bodies and the mind-body relationship, yet our understanding of aging experiences and health care practices can be limited by an overreliance on biomedical or social constructionist approaches alone. This paper offers a conceptual exploration of embodiment as an innovative approach to enhance our understandings of aging bodies and health in physiotherapy practice. Embodiment attends to body and mind, nature and culture, structure and agency, while appreciating differences in aging bodies and health in aging. Conclusions consider embodiment in the practice and disciplinary discourse of contemporary physiotherapy, specifically, considering the ways embodied perspectives can support therapists in their health care practice and relationships with people with aging bodies. PMID- 27253334 TI - Responsiveness of the Berg Balance Scale in patients early after stroke. AB - The Berg Balance Scale (BBS) has previously shown good measurement properties. However, its ability to detect important change in patients early after stroke is still unknown. The purpose of the present study was to determine the minimal important change (MIC) and its relation to the minimal detectable change (MDC) for BBS in patients early after stroke. This prospective follow-up study included patients within the first 2 weeks after onset of stroke. The BBS, Barthel Index, and Scandinavian Stroke Scale were obtained at inclusion and 1 month later. At the follow-up assessment, the Patient Global Impression of Change was obtained. A receiver operating characteristic (ROC) curve was used to calculate the cut-off value for the MIC. Fifty-two patients (mean age of 78.7, SD 8.5 years) were included. All measures showed a significant improvement from baseline to follow up. The ROC analysis identified a MIC of >=6 BBS points, while the MDC was 5.97 BBS points at the 80% confidence level. This study shows that a change of 6 BBS point or more can be considered an important change for patients in the sub-acute phase after stroke, which also represents an 80% probability of exceeding the measurement error. A total of 80% of unchanged patients would display random fluctuations within the bounds of MDC80, while 20% of unchanged patients would exceed MDC80. PMID- 27253335 TI - The effect of core stability and general exercise on abdominal muscle thickness in non-specific chronic low back pain using ultrasound imaging. AB - BACKGROUND: There is a controversy regarding whether core stability exercise (CSE) is more effective than general exercise (GE) for chronic LBP. To compare different exercises regarding their effect on improving back strength and stability, performance of abdominal muscles is a useful index. Ultrasound imaging for measuring muscle thickness could be used to assess muscle performance. OBJECTIVE: The aim of this study was to compare CSE and GE in chronic LBP using ultrasound imaging for measurement of thickness of the deep stabilizing and main global trunk muscles in non-specific chronic LBP. METHODS: Each program included 16 training sessions three times a week. Using ultrasound imaging, four transabdominal muscle thickness were measured before and after the intervention. Disability and pain were measured as secondary outcomes. RESULTS: After the intervention on participants (n = 43), a significant increase in muscle thickness (hypertrophy) was seen only in right and left rectus abdominis in the GE group, but significant difference to the CSE group was only on the right side. Disability and pain reduced within the groups without a significant difference in the change between them. CONCLUSIONS: The present results provided evidence that only GE increased right and left rectus muscle thickness. The only significant difference between CSE and GE groups was the right rectus thickness. As rectus is a global muscle, the effect of GE on strength improvement (one side stronger than the other) may have a negative effect on motor control of lumbopelvic muscles and possibly increase the risk of back pain occurring or becoming worse, though this was not observed in the present study. PMID- 27253336 TI - Using simulation pedagogy to teach clinical education skills: A randomized trial. AB - INTRODUCTION: Supervision of students is a key role of senior physiotherapy clinicians in teaching hospitals. The objective of this study was to test the effect of simulated learning environments (SLE) on educators' self-efficacy in student supervision skills. METHODS: A pilot prospective randomized controlled trial with concealed allocation was conducted. Clinical educators were randomized to intervention (SLE) or control groups. SLE participants completed two 3-hour workshops, which included simulated clinical teaching scenarios, and facilitated debrief. Standard Education (StEd) participants completed two online learning modules. Change in educator clinical supervision self-efficacy (SE) and student perceptions of supervisor skill were calculated. Between-group comparisons of SE change scores were analyzed with independent t-tests to account for potential baseline differences in education experience. RESULTS: Eighteen educators (n = 18) were recruited (SLE [n = 10], StEd [n = 8]). Significant improvements in SE change scores were seen in SLE participants compared to control participants in three domains of self-efficacy: (1) talking to students about supervision and learning styles (p = 0.01); (2) adapting teaching styles for students' individual needs (p = 0.02); and (3) identifying strategies for future practice while supervising students (p = 0.02). CONCLUSIONS: This is the first study investigating SLE for teaching skills of clinical education. SLE improved educators' self-efficacy in three domains of clinical education. Sample size limited the interpretation of student ratings of educator supervision skills. Future studies using SLE would benefit from future large multicenter trials evaluating its effect on educators' teaching skills, student learning outcomes, and subsequent effects on patient care and health outcomes. PMID- 27253337 TI - Construct validity of the Modified Gait Efficacy Scale in older females. AB - There are few well-validated tools that focus on the assessment of walking confidence in older adults. The main objective of this study was to assess construct validity of the 10-item Modified Gait Efficacy Scale (mGES) as a measure of walking confidence in older adults. Twenty-four older females completed the mGES, the 16-item Activities-specific Balance Confidence (ABC-16) scale, and the Senior Fitness Test (SFT). Construct validity of the mGES was evaluated by quantifying relationships between the mGES and the ABC-16 and the SFT, and by examining the ability of the mGES to discriminate between known groups (no/lower fear of falling versus higher fear of falling). There was a strong correlation between mGES and the ABC-16 scale (rs = 0.85; p < 0.001). The mGES was significantly associated with SFT components that required lower extremity strength, stepping aerobic endurance, and walking agility and dynamic balance (rs = 0.45 to 0.61; p < 0.05). Relationships between the mGES and number of arm curls in 30 s, chair sit and reach test, and back scratch test were weak (rs = 0.13-0.25; p > 0.05). Mean mGES score was 91.5% in a no/lower fear of falling group, while it was 81.4% in a higher fear group (p = 0.22). There was a trend toward a significant difference in the unstandardized residuals derived from regression of ranked mGES scores on ranked covariate (age and 8 foot up and go) scores, between the no/lower versus higher fear of falling group (p = 0.095). These results support construct validity of the mGES as a measure of gait self efficacy in community-dwelling older females. PMID- 27253339 TI - Corrigendum. PMID- 27253338 TI - Corrigendum. PMID- 27253340 TI - Surface Adsorption from the Exchange-Hole Dipole Moment Dispersion Model. AB - The accurate calculation of intermolecular interaction energies with density functional theory requires methods that include a treatment of long-range, nonlocal dispersion correlation. In this work, we explore the ability of the exchange-hole dipole moment (XDM) dispersion correction to model molecular surface adsorption. Adsorption energies are calculated for six small aromatic molecules (benzene, furan, pyridine, thiophene, thiophenol, and benzenediamine) and the four DNA nucleobases (adenine, thymine, guanine, and cytosine) on the (111) surfaces of the three coinage metals (copper, silver, and gold). For benzene, where the experimental reference data is most precise, the mean absolute error in the computed absorption energies is 0.04 eV. For the other aromatic molecules, the computed binding energies are found to be within 0.09 eV of the available reference data, on average, which is well below the expected experimental uncertainties for temperature-programmed desorption measurements. Unlike other dispersion-corrected functionals, adequate performance does not require changes to the canonical XDM implementation, and the good performance of XDM is explained in terms of the behavior of the exchange hole. Additionally, the base functional employed (B86bPBE) is also optimal for molecular studies, making B86bPBE-XDM an excellent candidate for studying chemistry on material surfaces. Finally, the noncovalent interaction (NCI) plot technique is shown to detect adsorption effects in real space on the order of tenths of an eV. PMID- 27253350 TI - Engineering Porous Organic Cage Crystals with Increased Acid Gas Resistance. AB - Both known and new CC3-based porous organic cages are prepared and exposed to acidic SO2 in vapor and liquid conditions. Distinct differences in the stability of the CC3 cages exist depending on the chirality of the diamine linkers used. The acid catalyzed CC3 degradation mechanism is probed via in situ IR and a degradation pathway is proposed and supported with computational results. CC3 crystals synthesized with racemic mixtures of diaminocyclohexane exhibited enhanced stability compared to CC3-R and CC3-S. Confocal fluorescent microscope images reveal that the stability difference in CC3 species originates from an abundance of mesoporous grain boundaries in CC3-R and CC3-S, allowing facile access of aqueous SO2 throughout the crystal, promoting decomposition. These grain boundaries are absent from CC3 crystals made with racemic linkers. PMID- 27253351 TI - Imaging in glaucoma care pathways in the UK. AB - Glaucoma is an incurable disease of the eye that affects 2% of over 40s in the United Kingdom and 5% of those over 80. The National Institute for Health and Care Excellence (NICE) estimates that the disease affects around 480,000 people in the United Kingdom, with over a million glaucoma-related hospital outpatient appointments each year. This paper aims to establish the care pathways for glaucoma across the United Kingdom and the perceived value of imaging. A questionnaire was distributed to members of the Ophthalmic Imaging Association to identify imaging protocols with glaucoma; results indicated that there was variation between hospitals. The perceived clinical value of imaging from staff involved in the pathway was also explored. PMID- 27253352 TI - Cloning, expression and characterization of xylose isomerase from the marine bacterium Fulvimarina pelagi in Escherichia coli. AB - Production of a xylose isomerase (XI) with high tolerance to the inhibitors xylitol and calcium, and high activity at the low pH and temperature conditions characteristic of yeast fermentations, is desirable for a simultaneous isomerization/fermentation process for cellulosic ethanol production. A putative XI gene (xylA) from the marine bacterium Fulvimarina pelagi was identified by sequence analysis of the F. pelagi genome, and was PCR amplified, cloned, and expressed in Escherichia coli. The rXI was produced in shake flask and fed-batch fermentations using glucose as the growth substrate. The optimum pH for rXI was approximately 7, although activity was evident at pH as low as 5.5. The purified rXI had a molecular weight in 160 kDA, a Vmax of 0.142 U/mg purified rXI, and a KM for xylose in the range of 1.75-4.17 mM/L at pH 6.5 and a temperature of 35 degrees C. The estimated calcium and xylitol KI values for rXI in cell-free extracts were 2,500 mg/L and >50 mM, respectively. The low KM of the F. pelagi xylose isomerase is consistent with the low nutrient conditions of the pelagic environment. These results indicate that Ca2+ and xylitol are not likely to be inhibitory in applications employing the rXI from F. pelagi to convert xylose to xylulose in fermentations of complex biomass hydrolysates. A higher Vmax at low pH (<6) and temperature (30 degrees C) would be preferable for use in biofuels production. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1230-1237, 2016. PMID- 27253355 TI - Acute Genitourinary Swelling and Erythema as Presenting Symptoms of Henoch Schonlein Purpura. AB - Henoch-Schonlein purpura (HSP) may present in a variety of ways, most commonly with joint pain or the distinctive palpable purpura. Genitourinary manifestations of HSP are less common and may precede the classic signs and symptoms of HSP, making the diagnosis difficult. We report a case of a 19-month-old boy with penile and scrotal erythema and swelling at presentation who was later diagnosed with HSP. PMID- 27253353 TI - Psychiatric Comorbidity Among Egyptian Patients With Opioid Use Disorders Attributed to Tramadol. AB - OBJECTIVE: Opioid use disorders attributed to tramadol (OUD-T) is a public health problem in Egypt. The objective of this study was to assess the psychiatric comorbidity among patients with opioid use disorder attributed to tramadol. METHODS: This study included 100 patients with opioid use disorders attributed to tramadol (according to DSM-IV-TR) and 100 control persons (matched for age, sex, and education), who were recruited from Zagazig University Hospital, Egypt. The participants were interviewed using Structured Clinical Interview for DSM disorders (SCID-I and SCID-II), Addiction Severity Index scale (patients), and urine screening for drugs. RESULTS: Twenty-four percent of the patients used tramadol only (pure tramadol group), whereas 76% of the patients used other substances in addition to tramadol (polysubstance group). Most (91%) of the patients had tramadol dependence. Forty-nine percent of the patients had psychiatric comorbidity, especially mood disorders (59.2%), whereas only 24% of the control persons had psychiatric comorbidity, especially anxiety disorders (83.3%). The most common personality disorders among patients were borderline (24%) and antisocial (22%), whereas in control persons, the most common personality disorders were obsessive compulsive personality disorder (8%) and the avoidant personality disorder (7%). Cluster B (76.6%) was the most common category among patients (compared with 25.8% in control persons), whereas cluster C (51.6%) was the most common category among control persons (compared with 15.6% in patients). CONCLUSIONS: Most of the patients were dependent on tramadol, and approximately 3 out of 4 used many substances. Almost half of the patients had psychiatric comorbidity, and approximately 3 out of 4 had cluster B personality disorders. PMID- 27253354 TI - Chimeric antigen receptor-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-cell acute lymphoblastic leukemia and enhance survival. AB - Pre-emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine-induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft-versus-host-disease. CIK cells are a heterogeneous effector cell population including T cells (CD3(+) CD56(-) ), natural killer (NK) cells (CD3(-) CD56(+) ) and natural killer T (T-NK) cells (CD3(+) CD56(+) ) that exhibit non-major histocompatibility complex (MHC)-restricted cytotoxicity and are generated by ex vivo expansion of peripheral blood mononuclear cells in the presence of interferon (IFN)-gamma, anti-CD3 antibody, interleukin-2 (IL-2) and interleukin-15 (IL-15). To facilitate selective target-cell recognition and enhance specific cytotoxicity against B-cell acute lymphoblastic leukemia (B ALL), we transduced CIK cells with a lentiviral vector encoding a chimeric antigen receptor (CAR) that carries a composite CD28-CD3zeta domain for signaling and a CD19-specific scFv antibody fragment for cell binding (CAR 63.28.z). In vitro analysis revealed high and specific cell killing activity of CD19-targeted CIK/63.28.z cells against otherwise CIK-resistant cancer cell lines and primary B ALL blasts, which was dependent on CD19 expression and CAR signaling. In a xenograft model in immunodeficient mice, treatment with CIK/63.28.z cells in contrast to therapy with unmodified CIK cells resulted in complete and durable molecular remissions of established primary pre-B-ALL. Our results demonstrate potent antileukemic activity of CAR-engineered CIK cells in vitro and in vivo, and suggest this strategy as a promising approach for adoptive immunotherapy of refractory pre-B-ALL. PMID- 27253359 TI - Acute Disseminated Encephalomyelitis. PMID- 27253357 TI - Altered Mental Status in a Child With an Unwitnessed Fall: A Case Report. AB - We report a case of altered mental status in a 5-year-old boy who presented to the emergency department after presumed head trauma. A computed tomography head was conducted and its findings were normal, and the boy was discharged home. He returned the next day with persistent altered mental status and was found to have an abnormal MR brain suggestive of embolic strokes. An echocardiogram revealed a large atrial mass that was later confirmed by pathology to be an atrial myxoma. This is a unique and, to our knowledge, unreported presentation of a known but rare disease process in a pediatric patient. PMID- 27253358 TI - Acute Disseminated Encephalomyelitis. AB - Acute disseminated encephalomyelitis is a primarily pediatric, immune-mediated disease characterized by demyelination and polyfocal neurologic symptoms that typically occur after a preceding viral infection or recent immunization. This article presents the pathophysiology, diagnostic criteria, and magnetic resonance imaging characteristics of acute disseminated encephalomyelitis. We also present evaluation and management strategies. PMID- 27253356 TI - Treatment of Severe Hypervolemic Hyponatremia in a Child With Pneumonia. AB - A 21-month-old boy came to our attention because of pneumonia. His weight increased before presentation, and his blood test results showed hyponatremia (116 mEq/L), low plasma osmolarity (241 mOsm/L), and high urine osmolarity (435 mOsm/L). He was treated with 0.9% sodium chloride solution and intravenous furosemide, and sodium levels rose up to 135 mEq/L in 36 hours. No standard treatment is available for severe hyponatremia in children. The use of vaptans in pediatric patients is described in literature, but it lacks evidence about safety and effectiveness. We suggest that furosemide administration plus salt replacement is effective in restoring normal values of plasma sodium concentration in severe euvolemic and hypervolemic hyponatremia. PMID- 27253360 TI - Abdominal Cerebrospinal Fluid Pseudocyst Diagnosed by Point-of-Care Ultrasound. AB - Abdominal cerebrospinal fluid pseudocyst is an uncommon complication of ventriculoperitoneal shunt and is seen more commonly in the pediatric population. The diagnosis of an abdominal cerebrospinal fluid pseudocyst is typically made by ultrasonography, which demonstrates a simple or loculated fluid collection in the abdomen. We present a case of abdominal pseudocyst diagnosed by point-of-care ultrasound. PMID- 27253363 TI - Pediatric Emergency Medicine: Legal Briefs. PMID- 27253362 TI - A 5-Year-Old Boy With an Acute Onset of Emesis, and Throat and Chest Pain, After Taking a Drink. PMID- 27253361 TI - Essentials of PEM Fellowship Part 2: The Profession in Entrustable Professional Activities. AB - This article is the second in a 7-part series that aims to comprehensively describe the current state and future directions of pediatric emergency medicine (PEM) fellowship training from the essential requirements to considerations for successfully administering and managing a program to the careers that may be anticipated upon program completion. This article describes the development of PEM entrustable professional activities (EPAs) and the relationship of these EPAs with existing taxonomies of assessment and learning within PEM fellowship. It summarizes the field in concepts that can be taught and assessed, packaging the PEM subspecialty into EPAs. PMID- 27253364 TI - ECGs in the ED. PMID- 27253365 TI - Zika Virus, Microcephaly, and Ocular Findings-Reply. PMID- 27253366 TI - Potentially Unsafe Activities and Living Conditions of Older Adults with Dementia. AB - OBJECTIVES: To examine the prevalence of dementia in the absence of a reported dementia diagnosis and whether potentially unsafe activities and living conditions vary as a function of dementia diagnosis status in a nationally representative sample of older adults. DESIGN: Observational cohort study. SETTING: Community. PARTICIPANTS: Medicare beneficiaries aged 65 and older enrolled in the National Health and Aging Trends Study (N = 7,609). MEASUREMENTS: Participants were classified into four groups based on self-report of dementia diagnosis, proxy screening interview, and cognitive testing: probable dementia with reported dementia diagnosis (n = 457), probable dementia without reported dementia diagnosis (n = 581), possible dementia (n = 996), or no dementia (n = 5,575). Potentially unsafe activities (driving, preparing hot meals, managing finances or medications, attending doctor visits alone) and living conditions (falls, living alone, and unmet needs) were examined according to dementia status subgroups in stratified analyses and multivariate models, adjusting for sociodemographic factors, medical comorbidities, and physical capacity. RESULTS: The prevalence of driving (22.9%), preparing hot meals (31.0%), managing finances (21.9%), managing medications (36.6%), and attending doctor visits alone (20.6%) was lowest in persons with probable dementia; however, but in persons with probable dementia, the covariate-adjusted rates of driving, preparing hot meals, managing finances, managing medications, and attending doctor visits alone were significantly higher in those without reported dementia diagnosis than in those with reported diagnosis (all odds ratios >=2.00, all P < .01). CONCLUSION: Older adults with probable dementia who are not aware of a dementia diagnosis are more likely to report engaging in potentially unsafe behaviors. Understanding the prevalence of potentially unsafe activities and living conditions can help clinicians focus safety screening and counseling in older adults with diagnosed or suspected dementia. PMID- 27253368 TI - Naphthalenediimide-alt-Fused Thiophene D-A Copolymers for the Application as Acceptor in All-Polymer Solar Cells. AB - Three n-type alternating D-A copolymers based on a naphthalenediimide (NDI) acceptor (A) unit and three different donor (D) units with varied electron donating strength including thiophene (P(NDI-T)), thieno[3,2-b]thiophene (P(NDI TT)), and thieno[3,2-b;4,5-b]dithiophene (P(NDI-TDT)), were synthesized, for the application as acceptor materials in all-polymer solar cells (all-PSCs). The effect of the donor units of thiophene, thienothiophene (TT) and thienodithiophene (TDT) on the physicochemical and photovoltaic properties of the n-type D-A copolymers was systematically investigated. It was found that the absorption spectrum is red-shifted and the energy band gap (Eg ) is reduced for the NDI-based D-A copolymers with increasing number of thiophene rings in the thiophene or fused thiophene donor units. All-PSCs were fabricated with the medium band gap conjugated polymer J51 (Eg of ca 1.9 eV) as polymer donor and the n-type D-A copolymers as acceptor. The power conversion efficiency reached 2.59 %, 3.70 % and 5.10 % for the all-PSCs with P(NDI-T), P(NDI-TT), and P(NDI-TDT) as acceptor, respectively. The results indicate that a larger conjugated fused molecular plane with more thiophene rings as donor units in the NDI-based D-A copolymers is beneficial to reduce the band gap, broaden the absorption and enhance the photovoltaic performance of n-type D-A copolymer acceptors. PMID- 27253367 TI - We Remember... Elders' Memories and Perceptions of Sleeping Sickness Control Interventions in West Nile, Uganda. AB - The traditional role of African elders and their connection with the community make them important stakeholders in community-based disease control programmes. We explored elders' memories related to interventions against sleeping sickness to assess whether or not past interventions created any trauma which might hamper future control operations. Using a qualitative research framework, we conducted and analysed twenty-four in-depth interviews with Lugbara elders from north western Uganda. Participants were selected from the villages inside and outside known historical sleeping sickness foci. Elders' memories ranged from examinations of lymph nodes conducted in colonial times to more recent active screening and treatment campaigns. Some negative memories dating from the 1990s were associated with diagnostic procedures, treatment duration and treatment side effects, and were combined with memories of negative impacts related to sleeping sickness epidemics particularly in HAT foci. More positive observations from the recent treatment campaigns were reported, especially improvements in treatment. Sleeping sickness interventions in our research area did not create any permanent traumatic memories, but memories remained flexible and open to change. This study however identified that details related to medical procedures can remain captured in a community's collective memory for decades. We recommend more emphasis on communication between disease control programme planners and communities using detailed and transparent information distribution, which is not one directional but rather a dialogue between both parties. PMID- 27253370 TI - The Small-RNA Profiles of Almond (Prunus dulcis Mill.) Reproductive Tissues in Response to Cold Stress. AB - Spring frost is an important environmental stress that threatens the production of Prunus trees. However, little information is available regarding molecular response of these plants to the frost stress. Using high throughput sequencing, this study was conducted to identify differentially expressed miRNAs, both the conserved and the non-conserved ones, in the reproductive tissues of almond tolerant H genotype under cold stress. Analysis of 50 to 58 million raw reads led to identification of 174 unique conserved and 59 novel microRNAs (miRNAs). Differential expression pattern analysis showed that 50 miRNA families were expressed differentially in one or both of almond reproductive tissues (anther and ovary). Out of these 50 miRNA families, 12 and 15 displayed up-regulation and down-regulation, respectively. The distribution of conserved miRNA families indicated that miR482f harbor the highest number of members. Confirmation of miRNAs expression patterns by quantitative real- time PCR (qPCR) was performed in cold tolerant (H genotype) alongside a sensitive variety (Sh12 genotype). Our analysis revealed differential expression for 9 miRNAs in anther and 3 miRNAs in ovary between these two varieties. Target prediction of miRNAs followed by differential expression analysis resulted in identification of 83 target genes, mostly transcription factors. This study comprehensively catalogued expressed miRNAs under different temperatures in two reproductive tissues (anther and ovary). Results of current study and the previous RNA-seq study, which was conducted in the same tissues by our group, provide a unique opportunity to understand the molecular basis of responses of almond to cold stress. The results can also enhance the possibility for gene manipulation to develop cold tolerant plants. PMID- 27253369 TI - Measuring IgA Anti-beta2-Glycoprotein I and IgG/IgA Anti-Domain I Antibodies Adds Value to Current Serological Assays for the Antiphospholipid Syndrome. AB - INTRODUCTION: Currently available clinical assays to detect antiphospholipid antibodies (aPL) test for IgG and IgM antibodies to cardiolipin (aCL) and beta2 glycoprotein I (abeta2GPI). It has been suggested that testing for IgA aPL and for antibodies to Domain I (DI), which carries the key antigenic epitopes of beta2GPI, could add value to these current tests. We performed an observational, multicenter cohort study to evaluate the utility of IgG, IgM and IgA assays to each of CL, beta2GPI and DI in APS. METHODS: Serum from 230 patients with APS (n = 111), SLE but not APS (n = 119), and 200 healthy controls were tested for IgG, IgM and IgA aCL, abeta2GPI and aDI activity. Patients with APS were further classified into thrombotic or obstetric APS. Logistic regression and receiver operator characteristic analyses were employed to compare results from the nine different assays. RESULTS: All assays displayed good specificity for APS; IgG aCL and IgG abeta2GPI assays however, had the highest sensitivity. Testing positive for IgA abeta2GPI resulted in a higher hazard ratio for APS compared to IgM abeta2GPI. Positive IgG, IgM or IgA aDI were all associated with APS, and in subjects positive for aCL and/or abeta2GPI, the presence of aDI raised the hazard ratio for APS by 3-5 fold. IgG aCL, abeta2GPI, aDI and IgA aDI were associated with thrombotic but not obstetric complications in patients with APS. CONCLUSION: Measuring IgG aDI and IgA abeta2GPI and aDI may be useful in the management of patients with APS, particularly thrombotic APS. PMID- 27253371 TI - A sigmaE-Mediated Temperature Gauge Controls a Switch from LuxR-Mediated Virulence Gene Expression to Thermal Stress Adaptation in Vibrio alginolyticus. AB - In vibrios, the expression of virulence factors is often controlled by LuxR, the master quorum-sensing regulator. Here, we investigate the interplay between LuxR and sigmaE, an alternative sigma factor, during the control of virulence-related gene expression and adaptations to temperature elevations in the zoonotic pathogen Vibrio alginolyticus. An rpoE null V. alginolyticus mutant was unable to adapt to various stresses and was survival-deficient in fish. In wild type V. alginolyticus, the expression of LuxR-regulated virulence factors increased as the temperature was increased from 22 degrees C to 37 degrees C, but mutants lacking sigmaE did not respond to temperature, indicating that sigmaE is critical for the temperature-dependent upregulation of virulence genes. Further analyses revealed that sigmaE binds directly to -10 and -35 elements in the luxR promoter that drive its transcription. ChIP assays showed that sigmaE binds to the promoter regions of luxR, rpoH and rpoE at high temperatures (e.g., 30 degrees C and 37 degrees C). However, at higher temperatures (42 degrees C) that induce thermal stress, sigmaE binding to the luxR promoter decreased, while its binding to the rpoH and rpoE promoters was unchanged. Thus, the temperature-dependent binding of sigmaE to distinct promoters appears to underlie a sigmaE-controlled switch between the expression of virulence genes and adaptation to thermal stress. This study illustrates how a conserved temperature response mechanism integrates into quorum-sensing circuits to regulate both virulence and stress adaptation. PMID- 27253372 TI - A Cross Sectional Study of the Prevalence of Preputial and Penile Scrotal Abnormalities among Clients Undergoing Voluntary Medical Male Circumcision in Soweto, South Africa. AB - OBJECTIVE: Medical device use is currently approved for males without preputial or major penile scrotal abnormalities for voluntary medical male circumcision (VMMC). We determined the prevalence of preputial abnormalities at a busy VMMC centre in Soweto, South Africa. METHODS: This was a cross-sectional record review at a high-volume VMMC centre in South Africa. We collated pre-circumcision demographic and genital examination findings from clients 8 years and older who had undergone VMMC from 01 May 2013 to 30 April 2014. Logistic regression was used to determine factors associated with preputial abnormalities. FINDINGS: During the review period, 6861 circumcisions were conducted and 37.1% (n = 2543) were 8-13 year olds. Median age was 15 years (IQR: 12-23 years). Fifteen percent (n = 1030) had preputial abnormalities or major penile scrotal abnormalities. Age specific prevalence of preputial or major genital abnormalities were 27.3%, 10.6% and 6.0% in 8-13, 14-18 and > 18 year olds respectively. The odds of preputial or major penile scrotal abnormality were higher in younger clients aged 8-13 years (OR = 5.9; 95% CI = 4.8-7.1) and 14-18 years (OR = 1.9; 95% CI = 1.5-2.4) compared to older clients above18 years and in those testing for HIV outside our clinic network (OR = 1.9; 95% CI = 1.4-2.7). CONCLUSION: The high prevalence of preputial and penile scrotal abnormalities observed suggests a need for VMMC sites to provide for both open surgical and devices methods in the provision of VMMC services. This is especially so among young male subjects presenting themselves for VMMC services at the various sites being developed in sub Saharan African countries. PMID- 27253376 TI - Effect of Interpersonal Interaction on Festinating Gait Rehabilitation in Patients with Parkinson's Disease. AB - Although human walking gait rhythms are generated by native individual gait dynamics, these gait dynamics change during interactions between humans. A typical phenomenon is synchronization of gait rhythms during cooperative walking. Our previous research revealed that fluctuation characteristics in stride interval of subjects with Parkinson's disease changed from random to 1/f fluctuation as fractal characteristics during cooperative walking with the gait assist system Walk-Mate, which emulates a human interaction using interactive rhythmic cues. Moreover, gait dynamics were relearned through Walk-Mate gait training. However, the system's clinical efficacy was unclear because the previous studies did not focus on specific gait rhythm disorder symptoms. Therefore, this study aimed to evaluate the effect of Walk-Mate on festinating gait among subjects with Parkinson's disease. Three within-subject experimental conditions were used: (1) preinteraction condition, (2) interaction condition, and (3) postinteraction condition. The only difference between conditions was the interactive rhythmic cues generated by Walk-Mate. Because subjects with festinating gait gradually and involuntarily decreased their stride interval, the regression slope of stride interval as an index of severity of preinteraction festinating gait was elevated. The regression slope in the interaction condition was more gradual than during the preinteraction condition, indicating that the interactive rhythmic cues contributed to relieving festinating gait and stabilizing gait dynamics. Moreover, the gradual regression slope was carried over to the postinteraction condition, indicating that subjects with festinating gait have the potential to relearn stable gait dynamics. These results suggest that disordered gait dynamics are clinically restored through interactive rhythmic cues and that Walk-Mate may have the potential to assist therapists in more effective rehabilitation. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000012591. PMID- 27253377 TI - Particle Physics in High School: A Diagnose Study. AB - The science learning process improves when the contents are connected to students' lives. Particle physics has had a great impact in our society in the last years and has changed the theoretical picture about matter fundamental dynamics. Thus, we think that academic contents about matter components and interactions should be updated. With this study we aim to characterize the level of knowledge of high school students about this topic. We built a test with questions about classical atomic models, particle physics, recent discoveries, social implications and students opinions about it. Contrary to our first suspicion, students' answers show a high variability. They have new physics ideas and show a great interest towards modern concepts. We suggest including an updated view of this topic as part of the curriculum. PMID- 27253373 TI - EGFR Signal-Network Reconstruction Demonstrates Metabolic Crosstalk in EMT. AB - Epithelial to mesenchymal transition (EMT) is an important event during development and cancer metastasis. There is limited understanding of the metabolic alterations that give rise to and take place during EMT. Dysregulation of signalling pathways that impact metabolism, including epidermal growth factor receptor (EGFR), are however a hallmark of EMT and metastasis. In this study, we report the investigation into EGFR signalling and metabolic crosstalk of EMT through constraint-based modelling and analysis of the breast epithelial EMT cell model D492 and its mesenchymal counterpart D492M. We built an EGFR signalling network for EMT based on stoichiometric coefficients and constrained the network with gene expression data to build epithelial (EGFR_E) and mesenchymal (EGFR_M) networks. Metabolic alterations arising from differential expression of EGFR genes was derived from a literature review of AKT regulated metabolic genes. Signaling flux differences between EGFR_E and EGFR_M models subsequently allowed metabolism in D492 and D492M cells to be assessed. Higher flux within AKT pathway in the D492 cells compared to D492M suggested higher glycolytic activity in D492 that we confirmed experimentally through measurements of glucose uptake and lactate secretion rates. The signaling genes from the AKT, RAS/MAPK and CaM pathways were predicted to revert D492M to D492 phenotype. Follow-up analysis of EGFR signaling metabolic crosstalk in three additional breast epithelial cell lines highlighted variability in in vitro cell models of EMT. This study shows that the metabolic phenotype may be predicted by in silico analyses of gene expression data of EGFR signaling genes, but this phenomenon is cell-specific and does not follow a simple trend. PMID- 27253378 TI - Lipid-Albumin Nanoparticles (LAN) for Therapeutic Delivery of Antisense Oligonucleotide against HIF-1alpha. AB - Lipid-albumin nanoparticles (LAN) were synthesized for delivery of RX-0047, an antisense oligonucleotide (ASO) against the hypoxia inducible factor-1 alpha (HIF 1alpha) to solid tumor. These lipid nanoparticles (LNs) incorporated a human serum albumin-pentaethylenehexamine (HSA-PEHA) conjugate, which is cationic and can form electrostatic complexes with negatively charged oligonucleotides. The delivery efficiency of LAN-RX-0047 was investigated in KB cells and a KB murine xenograft model. When KB cells were treated with LAN-RX-0047, significant HIF 1alpha downregulation and enhanced cellular uptake were observed compared to LN RX-0047. LN-RX-0047 and LAN-RX-0047 showed similar cytotoxicity against KB cells with IC50 values of 19.3 +/- 3.8 and 20.1 +/- 4.2 MUM, respectively. LAN-RX-0047 was shown to be taken up by the cells via the macropinocytosis and caveolae mediated endocytosis pathways while LN-RX-0047 was taken up by cells via caveolae mediated endocytosis. In the KB xenograft tumor model, LAN-RX-0047 exhibited tumor suppressive activity and significantly reduced intratumoral HIF-1alpha expression compared to LN-RX-0047. Furthermore, LAN-RX-0047 greatly increased survival time of mice bearing KB-1 xenograft tumors at doses of either 3 mg/kg or 16 mg/kg. These results indicated that LAN-RX-0047 is a highly effective vehicle for therapeutic delivery of antisense agents to tumor. PMID- 27253380 TI - Priority Setting and Influential Factors on Acceptance of Pharmaceutical Recommendations in Collaborative Medication Reviews in an Ambulatory Care Setting - Analysis of a Cluster Randomized Controlled Trial (WestGem-Study). AB - BACKGROUND: Medication reviews are recognized services to increase quality of therapy and reduce medication risks. The selection of eligible patients with potential to receive a major benefit is based on assumptions rather than on factual data. Acceptance of interprofessional collaboration is crucial to increase the quality of medication therapy. OBJECTIVE: The research question was to identify and prioritize eligible patients for a medication review and to provide evidence-based criteria for patient selection. Acceptance of the prescribing general practitioner to implement pharmaceutical recommendations was measured and factors influencing physicians' acceptance were explored to obtain an impression on the extent of collaboration in medication review in an ambulatory care setting. METHODS: Based on data of a cluster-randomized controlled study (WestGem-study), the correlation between patient parameters and the individual performance in a medication review was calculated in a multiple logistic regression model. Physician's acceptance of the suggested intervention was assessed using feedback forms. Influential factors were analyzed. RESULTS: The number of drugs in use (p = 0.001), discrepancies between prescribed and used medicines (p = 0.014), the baseline Medication Appropriateness Index score (p<0.001) and the duration of the intervention (p = 0.006) could be identified as influential factors for a major benefit from a medication review, whereas morbidity (p>0.05) and a low kidney function (p>0.05) do not predetermine the outcome. Longitudinal patient care with repeated reviews showed higher interprofessional acceptance and superior patient benefit. A total of 54.9% of the recommendations in a medication review on drug therapy were accepted for implementation. CONCLUSIONS: The number of drugs in use and medication reconciliation could be a first rational step in patient selection for a medication review. Most elderly, multimorbid patients with polymedication experience a similar chance of receiving a benefit from a medication review. Longitudinal patient care should be preferred over confined medication reviews. The acceptance of medication reviews by physicians supports further implementation into health care systems. TRIAL REGISTRATION: ISRCTN ISRCTN41595373. PMID- 27253381 TI - Program Bytes: Satellite Meetings, SIGs, and AKEs at ISMB 2016. PMID- 27253379 TI - Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation. AB - Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART), and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9) potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART suppressed individuals (p = 0.002), more potently than vorinostat (p = 0.02). rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p<0.05). rGal-9 signals through N linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR<0.006) and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p<0.02) and with the quantity and binding avidity of circulating anti-HIV antibodies (p<0.009), suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies. PMID- 27253384 TI - Synthesis and functionalization of monodisperse near-ultraviolet and visible excitable multifunctional Eu(3+), Bi(3+):REVO4 nanophosphors for bioimaging and biosensing applications. AB - Near-ultraviolet and visible excitable Eu- and Bi-doped NPs based on rare earth vanadates (REVO4, RE = Y, Gd) have been synthesized by a facile route from appropriate RE precursors, europium and bismuth nitrate, and sodium orthovanadate, by homogeneous precipitation in an ethylene glycol/water mixture at 120 degrees C. The NPs can be functionalized either by a one-pot synthesis with polyacrylic acid (PAA) or by a Layer-by-Layer approach with poly(allylamine hydrochloride) (PAH) and PAA. In the first case, the particle size can also be tuned by adjusting the amount of PAA. The Eu- Bi-doped REVO4 based nanophosphors show the typical red luminescence of Eu(iii), which can be excited through an energy transfer process from the vanadate anions, resulting in a much higher luminescence intensity in comparison to the direct excitation of the europium cations. The incorporation of Bi into the REVO4 structure shifts the original absorption band of the vanadate anions towards longer wavelengths, giving rise to nanophosphors with an excitation maximum at 342 nm, which can also be excited in the visible range. The suitability of such nanophosphors for bioimaging and biosensing applications, as well as their colloidal stability in different buffer media of biological interest, their cytotoxicity, their degradability at low pH, and their uptake by HeLa cells have been evaluated. Their suitability for bioimaging and biosensing applications is also demonstrated. PMID- 27253383 TI - Freshwater Crayfish: A Potential Benthic-Zone Indicator of Nanosilver and Ionic Silver Pollution. AB - Nowadays, silver nanoparticles (AgNPs) are utilized in numerous applications, raising justified concerns about their release into the environment. This study demonstrates the potential to use freshwater crayfish as a benthic-zone indicator of nanosilver and ionic silver pollution. Crayfish were acclimated to 20 L aquaria filled with Hudson River water (HRW) and exposed for 14 days to widely used Creighton AgNPs and Ag(+) at doses of up to 360 MUg L(-1) to surpass regulated water concentrations. The uptake and distribution of Ag in over 650 exoskeletons, gills, hepatopancreas and muscles samples were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES) in conjunction with two complementary U.S. EPA-endorsed methods: the external calibration and the standard additions. Reflecting the environmental plasticity of the two investigated species, Orconectes virilis accumulated in a dose-dependent manner more Ag than Procambarus clarkii (on average 31% more Ag). Both species showed DNA damage and severe histological changes in the presence of Ag. However, Ag(+) generally led to higher Ag accumulations (28%) and was more toxic. By the harvest day, about 14 +/- 9% of the 360 MUg L(-1) of AgNP exposure in the HRW oxidized to Ag(+) and may have contributed to the observed toxicities and bioaccumulations. The hepatopancreas (1.5-17.4 MUg of Ag g(-1) of tissue) was identified as the best tissue-indicator of AgNP pollution, while the gills (4.5-22.0 MUg g(-1)) and hepatopancreas (2.5-16.7 MUg g(-1)) complementarily monitored the presence of Ag(+). PMID- 27253385 TI - Quality of Life and Mortality of Long-Term Colorectal Cancer Survivors in the Seattle Colorectal Cancer Family Registry. AB - BACKGROUND AND AIM: Because most colorectal cancer patients survive beyond five years, understanding quality of life among these long-term survivors is essential to providing comprehensive survivor care. We sought to identify personal characteristics associated with reported quality of life in colorectal cancer survivors, and sub-groups of survivors potentially vulnerable to very low quality of life. METHODS: We assessed quality of life using the Veterans RAND 12-item Health Survey within a population-based sample of 1,021 colorectal cancer survivors in the Seattle Colorectal Cancer Family Registry, approximately 5 years post-diagnosis. In this case-only study, mean physical component summary scores and mental component summary scores were examined with linear regression. To identify survivors with substantially reduced ability to complete daily tasks, logistic regression was used to estimate odds ratios for "very low" summary scores, defined as a score in the lowest decile of the reference US population. All cases were followed for vital status following QoL assessment, and mortality was analyzed with Cox proportional hazards regression. RESULTS: Lower mean physical component summary score was associated with older age, female sex, obesity, smoking, and diabetes or other co-morbidity; lower mean mental component summary score was associated with younger age and female sex. Higher odds of very low physical component summary score was associated with older age, obesity, less education, smoking, co-morbidities, and later stage at diagnosis; smoking was associated with higher odds of very low mental component summary score. A very low physical component score was associated with higher risk of mortality (hazard ratio (95% confidence interval): 3.97 (2.95-5.34)). CONCLUSIONS: Our results suggest that identifiable sub-groups of survivors are vulnerable to very low physical components of quality of life, decrements that may represent meaningful impairment in completing everyday tasks and are associated with higher risk of death. PMID- 27253382 TI - Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Impairs Host Defense in Experimental Melioidosis. AB - BACKGROUND: Triggering receptor expressed on myeloid cells (TREM) -1 and TREM-2 are key regulators of the inflammatory response that are involved in the clearance of invading pathogens. Melioidosis, caused by the "Tier 1" biothreat agent Burkholderia pseudomallei, is a common form of community-acquired sepsis in Southeast-Asia. TREM-1 has been suggested as a biomarker for sepsis and melioidosis. We aimed to characterize the expression and function of TREM-1 and TREM-2 in melioidosis. METHODOLOGY/PRINCIPAL FINDINGS: Wild-type, TREM-1/3 (Trem 1/3-/-) and TREM-2 (Trem-2-/-) deficient mice were intranasally infected with live B. pseudomallei and killed after 24, and/or 72 h for the harvesting of lungs, liver, spleen, and blood. Additionally, survival studies were performed. Cellular functions were further analyzed by stimulation and/or infection of isolated cells. TREM-1 and TREM-2 expression was increased both in the lung and liver of B. pseudomallei-infected mice. Strikingly, Trem-2-/-, but not Trem-1/3-/ , mice displayed a markedly improved host defense as reflected by a strong survival advantage together with decreased bacterial loads, less inflammation and reduced organ injury. Cellular responsiveness of TREM-2, but not TREM-1, deficient blood and bone-marrow derived macrophages (BMDM) was diminished upon exposure to B. pseudomallei. Phagocytosis and intracellular killing of B. pseudomallei by BMDM and alveolar macrophages were TREM-1 and TREM-2-independent. CONCLUSIONS/SIGNIFICANCE: We found that TREM-2, and to a lesser extent TREM-1, plays a remarkable detrimental role in the host defense against a clinically relevant Gram-negative pathogen in mice: TREM-2 deficiency restricts the inflammatory response, thereby decreasing organ damage and mortality. PMID- 27253386 TI - Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants. AB - CONTEXT: Several countries have reported a resurgence of pertussis in the last decades. This puts infants (especially <6 months) at risk of severe complications, because they are too young to be fully protected by vaccination. The global pertussis initiative has proposed pertussis vaccination of young infants' close contacts, in order to reduce pertussis transmission and the burden of the disease on infants. Our aim is to explore the perceived determinants (barriers and facilitators) of intention to accept vaccination among the possible target groups of pertussis vaccination for cocooning. Consideration of these determinants is necessary to optimise the uptake of the vaccination. METHODS: We conducted 13 focus groups and six individual semi-structured interviews with members of possible target groups for pertussis cocooning (i.e. parents, maternity assistants, midwives, and paediatric nurses) in the Netherlands. Here, both maternal pertussis vaccination as well as pertussis cocooning has not been implemented. The topic list was based on a literature review and a barrier framework. All interviews were transcribed verbatim and two researchers performed thematic content analysis. FINDINGS: The participants' risk perception, outcome expectations, general vaccination beliefs, moral norms, opinion of others, perceived autonomy, anticipated regret, decisional uncertainty, and perceived organisational barriers were all factors that influenced the intention to accept pertussis vaccination for cocooning. DISCUSSION: This study has identified nine perceived determinants that influence the intention to accept pertussis cocooning vaccination. We add the following determinants to the literature: perceived cost effectiveness (as a concept of outcome expectations), justice (as a concept of moral norms), anticipated regret, and decisional uncertainty. We recommend considering these determinants in vaccination programmes for pertussis cocooning vaccination. Experience, information and trust emerged as predominant themes within these determinants. These themes require particular attention in future research on vaccination acceptance, especially with regard to their role in use and implementation in policy and practice. PMID- 27253387 TI - Highly Thermally Conductive Composite Papers Prepared Based on the Thought of Bioinspired Engineering. AB - The rapid development of modern electronics and three-dimensional integration sets stringent requirements for efficient heat removal of thermal-management materials to ensure the long lifetime of the electronics. However, conventional polymer composites that have been used widely as thermal-management materials suffer from undesired thermal conductivity lower than 10 W m(-1) K(-1). In this work, we report a novel thermally conductive composite paper based on the thought of bioinspired engineering. The advantage of the bioinspired papers over conventional composites lies in that they possess a very high in-plane thermal conductivity up to 21.7 W m(-1) K(-1) along with good mechanical properties and high electrical insulation. We attribute the high thermal conductivity to the improved interfacial interaction between assembled components through the introduction of silver nanoparticles and the oriented structure based on boron nitride nanosheets and silicon carbide nanowires. This thought based on bioinspired engineering provides a creative opportunity for design and fabrication of novel thermally conductive materials, and this kind of composite paper has potential applications in powerful integrated microelectronics. PMID- 27253388 TI - Quantification of Stereochemical Communication in Metal-Organic Assemblies. AB - The derivation and application of a statistical mechanical model to quantify stereochemical communication in metal-organic assemblies is reported. The factors affecting the stereochemical communication within and between the metal stereocenters of the assemblies were experimentally studied by optical spectroscopy and analyzed in terms of a free energy penalty per "incorrect" amine enantiomer incorporated, and a free energy of coupling between stereocenters. These intra- and inter-vertex coupling constants are used to track the degree of stereochemical communication across a range of metal-organic assemblies (employing different ligands, peripheral amines, and metals); temperature dependent equilibria between diastereomeric cages are also quantified. The model thus provides a unified understanding of the factors that shape the chirotopic void spaces enclosed by metal-organic container molecules. PMID- 27253389 TI - Assimilating to Hierarchical Culture: A Grounded Theory Study on Communication among Clinical Nurses. AB - The purpose of this study was to generate a substantive model that accounts for the explanatory social processes of communication in which nurses were engaged in clinical settings in Korea. Grounded theory methodology was used in this study. A total of 15 clinical nurses participated in the in-depth interviews. "Assimilating to the hierarchical culture" emerged as the basic social process of communication in which the participants engaged in their work environments. To adapt to the cultures of their assigned wards, the nurses learned to be silent and engaged in their assimilation into the established hierarchy. The process of assimilation consisted of three phases based on the major goals that nurses worked to achieve: getting to know about unspoken rules, persevering within the culture, and acting as senior nurse. Seven strategies and actions utilized to achieve the major tasks emerged as subcategories, including receiving strong disapproval, learning by observing, going silent, finding out what is acceptable, minimizing distress, taking advantages as senior nurse, and taking responsibilities as senior nurse. The findings identified how the pattern of communication in nursing organizations affected the way in which nurses were assimilated into organizational culture, from individual nurses' perspectives. In order to improve the rigid working atmosphere and culture in nursing organizations and increase members' satisfaction with work and quality of life, managers and staff nurses need training that focuses on effective communication and encouraging peer opinion-sharing within horizontal relationships. Moreover, organization-level support should be provided to create an environment that encourages free expression. PMID- 27253390 TI - Structure and Sensilla of the Mouthparts of the Spotted Lanternfly Lycorma delicatula (Hemiptera: Fulgoromorpha: Fulgoridae), a Polyphagous Invasive Planthopper. AB - Mouthparts are among the most important sensory and feeding structures in insects and comparative morphological study may help explain differences in feeding behavior and diet breadth among species. The spotted lanternfly Lycorma delicatula (White) (Hemiptera: Fulgoromorpha: Fulgoridae) is a polyphagous agricultural pest originating in China, recently established and becoming widespread in Korea, and more recently introduced into eastern North America. It causes severe economic damage by sucking phloem sap and the sugary excrement produced by nymphs and adults serves as a medium for sooty mold. To facilitate future study of feeding mechanisms in this insect, the fine-structural morphology of mouthparts focusing on the distribution of sensilla located on the labium in adult L. delicatula was observed using a scanning electron microscope. The mouthparts consist of a small cone-shaped labrum, a tubular labium and a stylet fascicle consisting of two inner interlocked maxillary stylets partially surrounded by two shorter mandibular stylets similar to those found in other hemipteran insects. The five-segmented labium is unusual (most other Fulgoromorpha have four segments) and is provided with several types of sensilla and cuticular processes situated on the apex of its distal labial segment. In general, nine types of sensilla were found on the mouthparts. Six types of sensilla and four types of cuticular processes are present on sensory fields of the labial apex. The proposed taxonomic and functional significance of the sensilla are discussed. Morphological similarities in the interlocking mechanism of the stylets suggest a relationship between Fulgoromorpha and Heteroptera. PMID- 27253391 TI - Correction: Antigen-Specific Antibody Glycosylation Is Regulated via Vaccination. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005456.]. PMID- 27253395 TI - Virtual Simulations as Preparation for Lab Exercises: Assessing Learning of Key Laboratory Skills in Microbiology and Improvement of Essential Non-Cognitive Skills. AB - OBJECTIVE: To investigate if a virtual laboratory simulation (vLAB) could be used to replace a face to face tutorial (demonstration) to prepare students for a laboratory exercise in microbiology. METHODS: A total of 189 students who were participating in an undergraduate biology course were randomly selected into a vLAB or demonstration condition. In the vLAB condition students could use a vLAB at home to 'practice' streaking out bacteria on agar plates in a virtual environment. In the demonstration condition students were given a live demonstration from a lab tutor showing them how to streak out bacteria on agar plates. All students were blindly assessed on their ability to perform the streaking technique in the physical lab, and were administered a pre and post test to determine their knowledge of microbiology, intrinsic motivation to study microbiology, and self-efficacy in the field of microbiology prior to, and after the experiment. RESULTS: The results showed that there were no significant differences between the two groups on their lab scores, and both groups had similar increases in knowledge of microbiology, intrinsic motivation to study microbiology, as well as self-efficacy in the field of microbiology. CONCLUSION: Our data show that vLABs function just as well as face to face tutorials in preparing students for a physical lab activity in microbiology. The results imply that vLABs could be used instead of face to face tutorials, and a combination of virtual and physical lab exercises could be the future of science education. PMID- 27253396 TI - Ultrasensitive Detection of Low-Abundance Protein Biomarkers by Mass Spectrometry Signal Amplification Assay. AB - A mass spectrometry signal amplification method is developed for the ultrasensitive and selective detection of low-abundance protein biomarkers by utilizing tag molecules on gold nanoparticles (AuNPs). EpCAM and thrombin as model targets are captured by specific aptamers immobilized on the AuNPs. With laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS), the mass tag molecules are detected to represent the protein biomarkers. Benefiting from the MS signal amplification, the assay can achieve a limit of detection of 100 aM. The method is further applied to detect thrombin in fetal bovine serum and EpCAM in cell lysates to demonstrate its selectivity and feasibility in complex biological samples. With the high sensitivity and specificity, the protocol shows great promise for providing a new route to single-cell analysis and early disease diagnosis. PMID- 27253394 TI - Intracellular Spread of Rabies Virus Is Reduced in the Paralytic Form of Canine Rabies Compared to the Furious Form. AB - Studies of the furious and paralytic forms of canine rabies at the early stage of disease have shown a more rapid viral colonization of the cerebral hemispheres in the furious form, as measured by viral antigen within neuronal cell bodies and viral RNA levels. Measurement of cellular processes separate from neuronal cell body provides a visual record of the spread of rabies virus which occurs across synapses. In this study, the amount of rabies viral antigen within cell processes was quantitatively assessed by image analysis in a cohort of naturally rabies infected non-vaccinated dogs (5 furious and 5 paralytic) that were sacrificed shortly after developing illness. Measurements were taken at different levels of the spinal cord, brain stem, and cerebrum. Results were compared to the amount of rabies viral antigen in neuronal cell bodies. Generally, the amount of rabies viral antigen in cell processes decreased in a rostral direction, following the pattern for the amount of rabies viral antigen in neuronal cell bodies and the percentage of involved cell bodies. However, there was a delay in cell process involvement following cell body involvement, consistent with replication occurring in the cell body region and subsequent transport out to cell processes. Greater amounts of antigen were seen in cell processes in dogs with the furious compared to paralytic form, at all anatomic levels examined. This difference was even evident when comparing (1) neurons with similar amounts of antigen, (2) similar percentages of involved neurons, and (3) anatomic levels that showed 100% positive neurons. These findings suggest that intracellular transport of the virus may be slower in the paralytic form, resulting in slower viral propagation. Possible mechanisms might involve host-specific differences in intracellular virus transport. The latter could be cytokine-mediated, since previous studies have documented greater inflammation in the paralytic form. PMID- 27253393 TI - Longitudinal Changes in White Matter Tract Integrity across the Adult Lifespan and Its Relation to Cortical Thinning. AB - A causal link between decreases in white matter (WM) integrity and cortical degeneration is assumed, but there is scarce knowledge on the relationship between these changes across the adult human lifespan. We investigated changes in thickness throughout the cortical mantle and WM tract integrity derived from T1 and diffusion weighted magnetic resonance imaging (MRI) scans in 201 healthy adults aged 23-87 years over a mean interval of 3.6 years. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivity changes were calculated for forceps minor and major and eight major white matter tracts in each hemisphere by use of a novel automated longitudinal tractography constrained by underlying anatomy (TRACULA) approach. We hypothesized that increasing MD and decreasing FA across tracts would relate to cortical thinning, with some anatomical specificity. WM integrity decreased across tracts non-uniformly, with mean annual percentage decreases ranging from 0.20 in the Inferior Longitudinal Fasciculus to 0.65 in the Superior Longitudinal Fasciculus. For most tracts, greater MD increases and FA decreases related to more cortical thinning, in areas in part overlapping with but also outside the projected tract endings. The findings indicate a combination of global and tract-specific relationships between WM integrity and cortical thinning. PMID- 27253392 TI - Theoretical Insights into the Biophysics of Protein Bi-stability and Evolutionary Switches. AB - Deciphering the effects of nonsynonymous mutations on protein structure is central to many areas of biomedical research and is of fundamental importance to the study of molecular evolution. Much of the investigation of protein evolution has focused on mutations that leave a protein's folded structure essentially unchanged. However, to evolve novel folds of proteins, mutations that lead to large conformational modifications have to be involved. Unraveling the basic biophysics of such mutations is a challenge to theory, especially when only one or two amino acid substitutions cause a large-scale conformational switch. Among the few such mutational switches identified experimentally, the one between the GA all-alpha and GB alpha+beta folds is extensively characterized; but all-atom simulations using fully transferrable potentials have not been able to account for this striking switching behavior. Here we introduce an explicit-chain model that combines structure-based native biases for multiple alternative structures with a general physical atomic force field, and apply this construct to twelve mutants spanning the sequence variation between GA and GB. In agreement with experiment, we observe conformational switching from GA to GB upon a single L45Y substitution in the GA98 mutant. In line with the latent evolutionary potential concept, our model shows a gradual sequence-dependent change in fold preference in the mutants before this switch. Our analysis also indicates that a sharp GA/GB switch may arise from the orientation dependence of aromatic pi-interactions. These findings provide physical insights toward rationalizing, predicting and designing evolutionary conformational switches. PMID- 27253398 TI - Racial and Ethnic Differences in Electrocardiographic Features of Takotsubo Cardiomyopathy. PMID- 27253401 TI - Management of Ductal Carcinoma In Situ of the Breast: A Review. AB - IMPORTANCE: Ductal carcinoma in situ (DCIS) of the breast represents a disease process that continues to increase in incidence with treatment paradigms that continue to evolve. Greater access to long-term data from large observational studies addressing the natural history of the disease has contributed to changes in treatment paradigms and put into question traditional management strategies. OBSERVATIONS: While recent analyses have suggested that a more conservative approach to the management of DCIS without surgical intervention or radiation therapy may be advisable based on breast cancer mortality data, there is a lack of level 1 or prospective evidence to support the widespread adoption of these approaches. Currently, surgery remains the standard of care for the initial treatment of DCIS. Adjuvant radiation therapy (RT) has consistently demonstrated a reduction in the risk of local recurrence following breast-conserving surgery (BCS), even in "low-risk" populations of patients. Invasive recurrences following BCS are associated with increases in breast cancer mortality. Questions that remain to be answered include (1) what constitutes an acceptable risk of local recurrence, (2) what are the costs associated with managing local recurrences compared with RT given initially after BCS (particularly in light of data supporting shorter courses of RT), and (3) what are the benefits of endocrine therapy on local recurrence, and do they justify the additional toxic effects and potential noncompliance with their long-term administration? CONCLUSIONS AND RELEVANCE: Surgery and RT remain standard of care treatment options in the management of DCIS. Future studies are required to identify cohorts of patients in which RT can be safely omitted as well as to evaluate whether short-course RT alone may represent a better option than endocrine therapy with respect to compliance, toxic effects, cost and local control following BCS. PMID- 27253397 TI - Interleukin 1 Polymorphisms Contribute to Intervertebral Disc Degeneration Risk: A Meta-Analysis. AB - OBJECTIVE: We performed a meta-analysis to assess association between interleukin 1 (IL-1) polymorphisms and the risk of Intervertebral Disc Degeneration (IDD). BACKGROUND: A series of studies have investigated the association between common single nucleotide polymorphisms in IL-1 and IDD risk; however, the overall results are inconclusive. METHODS: Two independent investigators conducted a systematic search for relevant available studies. Allele frequencies were extracted from each study. The association between the IL-1alpha (+889C/T) or IL 1beta (+3954C/T) polymorphism and IDD risk was measured by odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Five and six studies, respectively, were ultimately included in the meta-analysis for the IL-1alpha (+889C/T) and IL 1beta (+3954C/T) polymorphism. The combined results showed that the IL-1alpha (+889C/T) polymorphism was significantly associated with increased susceptibility to IDD, particularly in Caucasians (TT versus CC: OR = 2.95, 95% CI: 1.45, 6.04; Pheterogeneity = 0.82; TT versus CC/CT: OR = 2.29, 95% CI: 1.18, 4.47; Pheterogeneity = 0.20). In contrast, the IL-1beta (+3954C/T) polymorphism showed a trend towards increased risk in Caucasians but no association in Asians. CONCLUSION: This meta-analysis suggested that the IL-1alpha (+889C/T) polymorphism is significantly associated with risk of IDD, especially in Caucasian populations. PMID- 27253399 TI - Structural and Functional Characterization of Aerobactin Synthetase IucA from a Hypervirulent Pathotype of Klebsiella pneumoniae. AB - Iron is a vital mineral nutrient required by virtually all life forms to prosper; pathogenic bacteria are no exception. Despite the abundance of iron within the human host, highly regulated iron physiology can result in exceedingly low levels of iron bioavailable to prospective invading bacteria. To combat this scarcity of iron, many pathogenic bacteria have acquired specific and efficient iron acquisition systems, which allow them to thrive in iron-deficient host environments. One of the more prominent bacterial iron acquisition systems involves the synthesis, secretion, and reuptake of small-molecule iron chelators known as siderophores. Aerobactin, a citrate-hydroxamate siderophore originally isolated nearly 50 years ago, is produced by a number of pathogenic Gram-negative bacteria. Aerobactin has recently been demonstrated to play a pivotal role in mediating the enhanced virulence of a particularly invasive pathotype of Klebsiella pneumoniae (hvKP). Toward further understanding of this key virulence factor, we report the structural and functional characterization of aerobactin synthetase IucA from a strain of hvKP. The X-ray crystal structures of unliganded and ATP-bound forms of IucA were solved, forming the foundation of our structural analysis. Small angle X-ray scattering (SAXS) data suggest that, unlike its closest structurally characterized homologues, IucA adopts a tetrameric assembly in solution. Finally, we employed activity assays to investigate the substrate specificity and determine the apparent steady-state kinetic parameters of IucA. PMID- 27253400 TI - Finasteride Enhances the Generation of Human Myeloid-Derived Suppressor Cells by Up-Regulating the COX2/PGE2 Pathway. AB - Myeloid-derived suppressor cells (MDSCs) have been known to be a key factor in the regulation of the immune system under numerous conditions such as tumors, infections, autoimmune diseases, and transplantations. In contrast to the proposed deleterious role of MDSCs in tumors and infections, MDSCs with their suppressive function are now proved to have the beneficial potential of suppressing the autoimmune response and promoting tolerance to transplantation. Therefore, the expansion of MDSCs could be a promising therapeutic strategy for many diseases. In this study, we aimed to identify FDA-approved drugs that could aid in the expansion of functional MDSCs. We performed a high-throughput screening (HTS) of FDA-approved drugs based on the in vitro human MDSC differentiation system and identified finasteride (FIN) to have the best potency to aid the generation of human MDSCs. The FIN-induced MDSCs were quite similar to monocytic MDSCs with regard to their surface phenotype, morphology, immunosuppressive function, and related gene expression. Next, we aimed to determine the mechanism of action of FIN and found that FIN induced the expansion of MDSCs through up-regulation of the COX2/PGE2 pathway by enhancing the activity of COX2 promoter. In addition, the administration of indomethacin (IND), a COX2 inhibitor, abrogated the effect of FIN. Based on these results, we suggested that FIN could find applications in the future in the expansion of MDSCs. Further development of FIN-like compounds could be a novel strategy for generating functional MDSCs for immunosuppressive therapies in various immune disorder conditions. PMID- 27253406 TI - Raptor hunted by caspases. PMID- 27253402 TI - Commentary: Mitochondrial DNA damage and loss in diabetes. AB - This commentary discusses damage and loss of mitochondrial DNA (mtDNA) in type 2 diabetes mellitus from both the clinical and experimental perspectives. Increasingly, an array of studies in experimental models and patients suggests that the cellular stresses of insulin resistance in type 2 diabetes damage mtDNA, leading to loss of mitochondrial genetic content. As such, mtDNA is emerging as both a valuable monitoring tool and translational preventive target for metabolic disease. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27253405 TI - A transcription factor 7-like 1-lipocalin 2 axis in the differentiation of keratinocytes. PMID- 27253403 TI - TMEM2 inhibits hepatitis B virus infection in HepG2 and HepG2.2.15 cells by activating the JAK-STAT signaling pathway. AB - We have previously observed the downregulation of TMEM2 in the liver tissue of patients with chronic hepatitis B virus (HBV) infection and in HepG2.2.15 cells with HBV genomic DNA. In the present study, we investigated the role and mechanism of TMEM2 in HepG2 and HepG2.2.15 during HBV infection HepG2 and HepG2.2.15. HepG2 shTMEM2 cells with stable TMEM2 knockdown and HepG2 TMEM2 and HepG2.2.15 TMEM2 cells with stable TMEM2 overexpression were established using lentivirus vectors. We observed reduced expression of TMEM2 in HBV-infected liver tissues and HepG2.2.15 cells. HBsAg, HBcAg, HBV DNA, and HBV cccDNA levels were significantly increased in HepG2 shTMEM2 cells but decreased in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells compared with naive HepG2 cells. On the basis of the western blotting results, the JAK-STAT signaling pathway was inhibited in HepG2 shTMEM2 cells but activated in HepG2 TMEM2 and HepG2.2.15 TMEM2 cells. In addition, reduced and increased expression of the antiviral proteins MxA and OAS1 was observed in TMEM2-silenced cells (HepG2 shTMEM2 cells) and TMEM2 overexpressing cells (HepG2 TMEM2 and HepG2.2.15 TMEM2 cells), respectively. The expression of Interferon regulatory factor 9 (IRF9) was not affected by TMEM2. However, we found that overexpression and knockdown of TMEM2, respectively, promoted and inhibited importation of IRF9 into nuclei. The luciferase reporter assay showed that IRF9 nuclear translocation affected interferon-stimulated response element activities. In addition, the inhibitory effects of TMEM2 on HBV infection in HepG2 shTMEM2 cells was significantly enhanced by pre-treatment with interferon but significantly inhibited in HepG2.2.15 TMEM2 cells by pre-treatment with JAK1 inhibitor. TMEM2 inhibits HBV infection in HepG2 and HepG2.2.15 by activating the JAK-STAT signaling pathway. PMID- 27253404 TI - Proteolytic degradation and potential role of onconeural protein cdr2 in neurodegeneration. AB - Cerebellar degeneration-related protein 2 (cdr2) is expressed in the central nervous system, and its ectopic expression in tumor cells of patients with gynecological malignancies elicits immune responses by cdr2-specific autoantibodies and T lymphocytes, leading to neurological symptoms. However, little is known about the regulation and function of cdr2 in neurodegenerative diseases. Because we found that cdr2 is highly expressed in the midbrain, we investigated the role of cdr2 in experimental models of Parkinson's disease (PD). We found that cdr2 levels were significantly reduced after stereotaxic injection of 1-methyl-4-phenylpyridinium (MPP(+)) into the striatum. cdr2 levels were also decreased in the brains of post-mortem PD patients. Using primary cultures of mesencephalic neurons and MN9D cells, we confirmed that MPP(+) reduces cdr2 in tyrosine hydroxylase-positive dopaminergic neuronal cells. The MPP(+)-induced decrease of cdr2 was primarily caused by calpain- and ubiquitin proteasome system mediated degradation, and cotreatment with pharmacological inhibitors of these enzymes or overexpression of calcium-binding protein rendered cells less vulnerable to MPP(+)-mediated cytotoxicity. Consequently, overexpression of cdr2 rescued cells from MPP(+)-induced cytotoxicity, whereas knockdown of cdr2 accelerated toxicity. Collectively, our findings provide insights into the novel regulatory mechanism and potentially protective role of onconeural protein during dopaminergic neurodegeneration. PMID- 27253410 TI - Continuous exposure of pancreatic cancer cells to dietary bioactive agents does not induce drug resistance unlike chemotherapy. AB - The repeated treatment of cancer cells with chemo- or radiotherapy induces therapy resistance, but it was previously unknown whether the same effect occurs upon continuous exposure of cancer cells to diet-derived chemopreventive agents. We elucidated this interesting question in pancreatic ductal adenocarcinoma, which is a highly aggressive cancer entity with a marked resistance toward gemcitabine and other cytotoxic drugs. The isothiocyanate sulforaphane, present in cruciferous vegetables, and the polyphenol quercetin, present in many fruits and vegetables induced apoptosis and reduced viability in gemcitabine-sensitive BxPC-3 cells but not in non-malignant ductal pancreas cells and mesenchymal stromal cells. In turn, BxPC-3 cells were treated with increasing concentrations of gemcitabine, sulforaphane or quercetin for more than 1 year and the surviving subclones Bx-GEM, Bx-SF and Bx-Q were selected, respectively. While Bx-GEM cells acquired a total resistance, Bx-SF or Bx-Q cells largely kept their sensitivity as proved by MTT assay, annexin staining and FACS analysis. The evaluation of the self-renewal-, differentiation- and migration-potential by colony formation, differentiation or migration assays demonstrated that cancer stem cell features were enriched in gemcitabine-resistant cells, but decreased in sulforaphane- and quercetin-long time-treated cells. These results were confirmed by orthotopic xenotransplantation of cancer cells to the mouse pancreas, where Bx-GEM formed large, Bx-Q small and Bx-SF cells almost undetectable tumors. An mRNA expression profiling array and subsequent gene set enrichment analysis and qRT-PCR confirmed that tumor progression markers were enriched in Bx-GEM, but reduced in Bx-SF and Bx-Q cells. This study demonstrates that the continuous exposure of pancreatic cancer cells to sulforaphane or quercetin does not induce resistance in surviving cells but reduces tumorigenicity by inhibition of tumor progression markers. These results highlight that cancer cells may not adapt to the preventive and therapeutic effects of a regular fruit- and vegetable-based diet. PMID- 27253417 TI - Free-Standing Copper Nanowire Network Current Collector for Improving Lithium Anode Performance. AB - Lithium metal is one of the most attractive anode materials for next-generation lithium batteries due to its high specific capacity and low electrochemical potential. However, the poor cycling performance and serious safety hazards, caused by the growth of dendritic and mossy lithium, has long hindered the application of lithium metal based batteries. Herein, we reported a rational design of free-standing Cu nanowire (CuNW) network to suppress the growth of dendritic lithium via accommodating the lithium metal in three-dimensional (3D) nanostructures. We demonstrated that as high as 7.5 mA h cm(-2) of lithium can be plated into the free-standing copper nanowire (CuNW) current collector without the growth of dendritic lithium. The lithium metal anode based on the CuNW exhibited high Coulombic efficiency (average 98.6% during 200 cycles) and outstanding rate performance owing to the suppression of lithium dendrite growth and high conductivity of CuNW network. Our results demonstrate that the rational nanostructural design of current collector could be a promising strategy to improve the performance of lithium metal anode enabling its application in next generation lithium-metal based batteries. PMID- 27253409 TI - Toll-like receptor 4 modulates the cochlear immune response to acoustic injury. AB - Acoustic overstimulation traumatizes the cochlea, resulting in auditory dysfunction. As a consequence of acoustic injury, the immune system in the cochlea is activated, leading to the production of inflammatory mediators and the infiltration of immune cells. However, the molecular mechanisms responsible for initiating these immune responses remain unclear. Here, we investigate the functional role of Toll-like receptor 4 (Tlr4), a cellular receptor that activates the innate immune system, in the regulation of cochlear responses to acoustic overstimulation. Using a Tlr4 knockout mouse model, we examined how Tlr4 deficiency affects sensory cell pathogenesis, auditory dysfunction and cochlear immune activity. We demonstrate that Tlr4 knockout does not affect sensory cell viability under physiological conditions, but reduces the level of sensory cell damage and cochlear dysfunction after acoustic injury. Together, these findings suggest that Tlr4 promotes sensory cell degeneration and cochlear dysfunction after acoustic injury. Acoustic injury provokes a site-dependent inflammatory response in both the organ of Corti and the tissues of the lateral wall and basilar membrane. Tlr4 deficiency affects these inflammatory responses in a site dependent manner. In the organ of Corti, loss of Tlr4 function suppresses the production of interleukin 6 (Il6), a pro-inflammatory molecule, after acoustic injury. By contrast, the production of inflammatory mediators, including Il6, persists in the lateral wall and basilar membrane. In addition to immune molecules, Tlr4 knockout inhibits the expression of major histocompatibility complex class II, an antigen-presenting molecule, in macrophages, suggesting that Tlr4 participates in the antigen-presenting function of macrophages after acoustic trauma. Together, these results suggest that Tlr4 regulates multiple aspects of the immune response in the cochlea and contributes to cochlear pathogenesis after acoustic injury. PMID- 27253411 TI - Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo. AB - Erianin, a natural product derived from Dendrobium chrysotoxum, has exhibited potential antitumor activity in various malignancies, including hepatocarcinoma, melanoma, and promyelocytic leukemia. Here we explored the effects of erianin on osteosarcoma (OS) in vitro and in vivo and further elucidated the underlying molecule mechanisms. In this study, we found that erianin potently suppressed cell viability in various OS cell lines. Treatment with erianin induced G2/M phase arrest, apoptosis, and autophagy in OS cells. Further studies showed that erianin-induced apoptosis and autophagy was attributed to reactive oxygen species (ROS), as N-acetyl cysteine (NAC), an ROS scavenger, attenuated them. Moreover, we found that erianin induced activation of c-Jun N-terminal kinase (JNK) signal pathway, which was also blocked by NAC. Downregulation of JNK by its specific inhibitor SP600125 could attenuate apoptosis and autophagy induced by erianin. Finally, erianin in vivo markedly reduced the growth with little organ-related toxicity. In conclusion, erianin induced cell cycle G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human OS. In light of these results, erianin may be a promising agent for anticancer therapy against OS. PMID- 27253407 TI - Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model. AB - Recent findings suggest that part of the anti-tumor effects of several chemotherapeutic agents require an intact immune system. This is in part due to the induction of immunogenic cell death. We have identified a gallotannin-rich fraction, obtained from Caesalpinia spinosa (P2Et) as an anti-tumor agent in both breast carcinoma and melanoma. Here, we report that P2Et treatment results in activation of caspase 3 and 9, mobilization of cytochrome c and externalization of annexin V in tumor cells, thus suggesting the induction of apoptosis. This was preceded by the onset of autophagy and the expression of immunogenic cell death markers. We further demonstrate that P2Et-treated tumor cells are highly immunogenic in vaccinated mice and induce immune system activation, clearly shown by the generation of interferon gamma (IFN-gamma) producing tyrosine-related protein 2 antigen-specific CD8+ T cells. Moreover, the tumor protective effects of P2Et treatment were abolished in immunodeficient mice, and partially lost after CD4 and CD8 depletion, indicating that P2Et's anti-tumor activity is highly dependent on immune system and at least in part of T cells. Altogether, these results support the hypothesis that the gallotannin-rich fraction P2Et's anti tumor effects are mediated to a great extent by the endogenous immune response following to the exposure to immunogenic dying tumor cells. PMID- 27253408 TI - Transglutaminase 2 has opposing roles in the regulation of cellular functions as well as cell growth and death. AB - Transglutaminase 2 (TG2) is primarily known as the most ubiquitously expressed member of the transglutaminase family with Ca(2+)-dependent protein crosslinking activity; however, this enzyme exhibits multiple additional functions through GTPase, cell adhesion, protein disulfide isomerase, kinase, and scaffold activities and is associated with cell growth, differentiation, and apoptosis. TG2 is found in the extracellular matrix, plasma membrane, cytosol, mitochondria, recycling endosomes, and nucleus, and its subcellular localization is an important determinant of its function. Depending upon the cell type and stimuli, TG2 changes its subcellular localization and biological activities, playing both anti- and pro-apoptotic roles. Increasing evidence indicates that the GTP-bound form of the enzyme (in its closed form) protects cells from apoptosis but that the transamidation activity of TG2 (in its open form) participates in both facilitating and inhibiting apoptosis. A difficulty in the study and understanding of this enigmatic protein is that opposing effects have been reported regarding its roles in the same physiological and/or pathological systems. These include neuroprotective or neurodegenerative effects, hepatic cell growth-promoting or hepatic cell death-inducing effects, exacerbating or having no effect on liver fibrosis, and anti- and pro-apoptotic effects on cancer cells. The reasons for these discrepancies have been ascribed to TG2's multifunctional activities, genetic variants, conformational changes induced by the immediate environment, and differences in the genetic background of the mice used in each of the experiments. In this article, we first report that TG2 has opposing roles like the protagonist in the novel Dr. Jekyll and Mr. Hyde, followed by a summary of the controversies reported, and finally discuss the possible reasons for these discrepancies. PMID- 27253415 TI - Endoplasmic reticulum stress eIF2alpha-ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced autophagy in kidney. AB - The heavy metal cadmium (Cd) is nephrotoxic. Recent studies show that autophagy plays an essential role in Cd-induced kidney injury. However, the mechanisms of Cd-induced kidney injury accompanied by autophagy are still obscure. In the present study, we first confirmed that Cd induced kidney damage and dysfunction, along with autophagy, both in vivo and in vitro. Then, we observed that cyclooxygenase-2 (COX-2) and the eIF2alpha-ATF4 pathway of endoplasmic reticulum (ER) stress were induced by Cd in both kidney tissues and cultured cells. Further studies showed that inhibition of COX-2 with celecoxib or RNA interference (RNAi) inhibited the Cd-induced autophagy in kidney cells. In addition, blocking ER stress with 4-phenylbutyrate or RNAi partially counteracted COX-2 overexpression and autophagy induced by Cd, which suggested that ER stress was required for Cd induced kidney autophagy. Significantly, our results showed that Cd activated ATF4 and induced its translocation to the nucleus. Knockdown of ATF4 inhibited Cd induced COX-2 overexpression. While COX-2 overexpression is involved in renal dysfunction, there is no prior report on the role of COX-2 in autophagy regulation. The results of the current study suggest a novel molecular mechanism that the ER stress eIF2alpha-ATF4 pathway-mediated COX-2 overexpression contributes to Cd-induced kidney autophagy and injury. The present study implies that COX-2 may be a potential target for therapy against Cd-induced nephrotoxicity. PMID- 27253418 TI - Subcutaneous versus sublingual immunotherapy. PMID- 27253416 TI - Guttiferone K impedes cell cycle re-entry of quiescent prostate cancer cells via stabilization of FBXW7 and subsequent c-MYC degradation. AB - Cell cycle re-entry by quiescent cancer cells is an important mechanism for cancer progression. While high levels of c-MYC expression are sufficient for cell cycle re-entry, the modality to block c-MYC expression, and subsequent cell cycle re-entry, is limited. Using reversible quiescence rendered by serum withdrawal or contact inhibition in PTEN(null)/p53(WT) (LNCaP) or PTEN(null)/p53(mut) (PC-3) prostate cancer cells, we have identified a compound that is able to impede cell cycle re-entry through c-MYC. Guttiferone K (GUTK) blocked resumption of DNA synthesis and preserved the cell cycle phase characteristics of quiescent cells after release from the quiescence. In vehicle-treated cells, there was a rapid increase in c-MYC protein levels upon release from the quiescence. However, this increase was inhibited in the presence of GUTK with an associated acceleration in c-MYC protein degradation. The inhibitory effect of GUTK on cell cycle re-entry was significantly reduced in cells overexpressing c-MYC. The protein level of FBXW7, a subunit of E3 ubiquitin ligase responsible for degradation of c-MYC, was reduced upon the release from the quiescence. In contrast, GUTK stabilized FBXW7 protein levels during release from the quiescence. The critical role of FBXW7 was confirmed using siRNA knockdown, which impaired the inhibitory effect of GUTK on c-MYC protein levels and cell cycle re-entry. Administration of GUTK, either in vitro prior to transplantation or in vivo, suppressed the growth of quiescent prostate cancer cell xenografts. Furthermore, elevation of FBXW7 protein levels and reduction of c-MYC protein levels were found in the xenografts of GUTK treated compared with vehicle-treated mice. Hence, we have identified a compound that is capable of impeding cell cycle re-entry by quiescent PTEN(null)/p53(WT) and PTEN(null)/p53(mut) prostate cancer cells likely by promoting c-MYC protein degradation through stabilization of FBXW7. Its usage as a clinical modality to prevent prostate cancer progression should be further evaluated. PMID- 27253412 TI - Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction. AB - Atherosclerosis is one of the most common vascular disorders. Endothelial cell (EC) dysfunction and vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. Long non-coding RNAs (lncRNAs) have been implicated in several biological processes and human diseases. Here we show that lncRNA-RNCR3 is expressed in ECs and VSMCs. RNCR3 expression is significantly upregulated in mouse and human aortic atherosclerotic lesions, and cultured ECs and VSMCs upon ox-LDL treatment in vitro. RNCR3 knockdown accelerates the development of atherosclerosis, aggravates hypercholesterolemia and inflammatory factor releases, and decreases EC and VSMC proliferation in vivo. RNCR3 knockdown also reduces the proliferation and migration, and accelerates apoptosis development of EC and VSMC in vitro. RNCR3 acts as a ceRNA, and forms a feedback loop with Kruppel-like factor 2 and miR-185-5p to regulate cell function. This study reveals that RNCR3 has an atheroprotective role in atherosclerosis, and its intervention is a promising strategy for treating atherosclerosis-related vascular dysfunction. PMID- 27253414 TI - A20 prevents chronic liver inflammation and cancer by protecting hepatocytes from death. AB - An important regulator of inflammatory signalling is the ubiquitin-editing protein A20 that acts as a break on nuclear factor-kappaB (NF-kappaB) activation, but also exerts important cytoprotective functions. A20 knockout mice are cachectic and die prematurely due to excessive multi-organ inflammation. To establish the importance of A20 in liver homeostasis and pathology, we developed a novel mouse line lacking A20 specifically in liver parenchymal cells. These mice spontaneously develop chronic liver inflammation but no fibrosis or hepatocellular carcinomas, illustrating an important role for A20 in normal liver tissue homeostasis. Hepatocyte-specific A20 knockout mice show sustained NF kappaB-dependent gene expression in the liver upon tumor necrosis factor (TNF) or lipopolysaccharide injection, as well as hepatocyte apoptosis and lethality upon challenge with sublethal doses of TNF, demonstrating an essential role for A20 in the protection of mice against acute liver failure. Finally, chronic liver inflammation and enhanced hepatocyte apoptosis in hepatocyte-specific A20 knockout mice was associated with increased susceptibility to chemically or high fat-diet-induced hepatocellular carcinoma development. Together, these studies establish A20 as a crucial hepatoprotective factor. PMID- 27253413 TI - A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment. AB - We have used polysome profiling coupled to microarray analysis to examine the translatome of a panel of peripheral blood (PB) B cells isolated from 34 chronic lymphocytic leukaemia (CLL) patients. We have identified a 'ribosome-related' signature in CLL patients with mRNAs encoding for ribosomal proteins and factors that modify ribosomal RNA, e.g. DKC1 (which encodes dyskerin, a pseudouridine synthase), showing reduced polysomal association and decreased expression of the corresponding proteins. Our data suggest a general impact of dyskerin dysregulation on the translational apparatus in CLL and importantly patients with low dyskerin levels have a significantly shorter period of overall survival following treatment. Thus, translational dysregulation of dyskerin could constitute a mechanism by which the CLL PB B cells acquire an aggressive phenotype and thus have a major role in oncogenesis. PMID- 27253422 TI - Spatial Distribution of Mycobacterium ulcerans in Buruli Ulcer Lesions: Implications for Laboratory Diagnosis. AB - BACKGROUND: Current laboratory diagnosis of Buruli ulcer (BU) is based on microscopic detection of acid fast bacilli, quantitative real-time PCR (qPCR), histopathology or cultivation. Insertion sequence (IS) 2404 qPCR, the most sensitive method, is usually only available at reference laboratories. The only currently available point-of-care test, microscopic detection of acid fast bacilli (AFB), has limited sensitivity and specificity. METHODOLOGY/ PRINCIPAL FINDINGS: Here we analyzed AFB positive tissue samples (n = 83) for the presence, distribution and amount of AFB. AFB were nearly exclusively present in the subcutis with large extracellular clusters being most frequently (67%) found in plaque lesions. In ulcerative lesions small clusters and dispersed AFB were more common. Beside this, 151 swab samples from 37 BU patients were analyzed by IS2404 qPCR and ZN staining in parallel. The amount of M. ulcerans DNA in extracts from swabs correlated well with the probability of finding AFB in direct smear microscopy, with 56.1% of the samples being positive in both methods and 43.9% being positive only in qPCR. By analyzing three swabs per patient instead of one, the probability to have at least one positive swab increased from 80.2% to 97.1% for qPCR and from 45% to 66.1% for AFB smear examination. CONCLUSION / SIGNIFICANCE: Our data show that M. ulcerans bacteria are primarily located in the subcutis of BU lesions, making the retrieval of the deep subcutis mandatory for examination of tissue samples for AFB. When laboratory diagnosis is based on the recommended less invasive collection of swab samples, analysis of three swabs from different areas of ulcerative lesions instead of one increases the sensitivity of both qPCR and of smear microscopy substantially. PMID- 27253421 TI - ACVR1B rs2854464 Is Associated with Sprint/Power Athletic Status in a Large Cohort of Europeans but Not Brazilians. AB - Skeletal muscle strength and mass, major contributors to sprint/power athletic performance, are influenced by genetics. However, to date, only a handful of genetic variants have been associated with sprint/power performance. The ACVR1B A allele (rs rs2854464) has previously been associated with increased muscle strength in non-athletic cohort. However, no follow-up and/or replications studies have since been conducted. Therefore, the aim of the present study was to compare the genotype distribution of ACVR1B rs2854464 between endurance athletes (E), sprint/power (S/P) athletes, mixed athletes (M), and non-athletic control participants in 1672 athletes (endurance athletes, n = 482; sprint/power athletes, n = 578; mixed athletes, n = 498) and 1089 controls (C) of both European Caucasians (Italian, Polish and Russians) and Brazilians. We have also compared the genotype distribution according to the athlete's level of competition (elite vs. sub-elite). DNA extraction and genotyping were performed using various methods. Fisher's exact test (adjusted for multiple comparisons) was used to test whether the genotype distribution of rs2854464 (AA, AG and GG) differs between groups. The A allele was overrepresented in S/P athletes compared with C in the Caucasian sample (adjusted p = 0.048), whereas there were no differences in genotype distribution between E athletes and C, in neither the Brazilian nor the Caucasian samples (adjusted p > 0.05). When comparing all Caucasian athletes regardless of their sporting discipline to C, we found that the A allele was overrepresented in athletes compared to C (adjusted p = 0.024). This association was even more pronounced when only elite-level athletes were considered (adjusted p = 0.00017). In conclusion, in a relatively large cohort of athletes from Europe and South America we have shown that the ACVR1B rs2854464 A allele is associated with sprint/power performance in Caucasians but not in Brazilian athletes. This reinforces the notion that phenotype-genotype associations may be ethnicity-dependent. PMID- 27253419 TI - 14-3-3gamma Prevents Centrosome Amplification and Neoplastic Progression. AB - More than 80% of malignant tumors show centrosome amplification and clustering. Centrosome amplification results from aberrations in the centrosome duplication cycle, which is strictly coordinated with DNA-replication-cycle. However, the relationship between cell-cycle regulators and centrosome duplicating factors is not well understood. This report demonstrates that 14-3-3gamma localizes to the centrosome and 14-3-3gamma loss leads to centrosome amplification. Loss of 14-3 3gamma results in the phosphorylation of NPM1 at Thr-199, causing early centriole disjunction and centrosome hyper-duplication. The centrosome amplification led to aneuploidy and increased tumor formation in mice. Importantly, an increase in passage of the 14-3-3gamma-knockdown cells led to an increase in the number of cells containing clustered centrosomes leading to the generation of pseudo bipolar spindles. The increase in pseudo-bipolar spindles was reversed and an increase in the number of multi-polar spindles was observed upon expression of a constitutively active 14-3-3-binding-defective-mutant of cdc25C (S216A) in the 14 3-3gamma knockdown cells. The increase in multi-polar spindle formation was associated with decreased cell viability and a decrease in tumor growth. Our findings uncover the molecular basis of regulation of centrosome duplication by 14-3-3gamma and inhibition of tumor growth by premature activation of the mitotic program and the disruption of centrosome clustering. PMID- 27253424 TI - Interstimulus Intervals and Sensory Modality Modulate the Impact of a Cognitive Task on Postural Control. AB - The present literature not only reveals the use of a wide variety of cognitive tasks but variability in their interaction with postural control. The question then arises, as to, whether postural control is sensitive to specific features of a cognitive task. The present experiment assessed the impact of cognitive tasks with interstimulus intervals (ISI) of varied duration and sensory modality on postural control in young adults. Seventeen participants (23.71 +/- 1.99 years old) were instructed to stand on a force platform while concurrently performing cognitive tasks with ISIs of two and 5 s. The tasks were presented both, auditorily and visually. The visual tasks consisted of counting the total occurrence of a single digit. The auditory tasks consisted of counting the total occurrence of a single letter. Performing the cognitive tasks with an ISI of 2 s resulted only in an increase in the anteroposterior mean power frequency. Presenting the tasks visually also significantly reduced area of 95% confidence ellipse and AP and mediolateral sway variability. These results may suggest that ISIs can modify postural performance by altering the allocation of attentional focus. Also, presenting tasks using a visual sensory modality appears to yield lower postural sway. PMID- 27253423 TI - Quantitative Assessment of Rectal Cancer Response to Neoadjuvant Combined Chemotherapy and Radiation Therapy: Comparison of Three Methods of Positioning Region of Interest for ADC Measurements at Diffusion-weighted MR Imaging. AB - Purpose To determine the impact of three different methods of region of interest (ROI) positioning for apparent diffusion coefficient (ADC) measurements on the assessment of complete response (CR) to neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer. Materials and Methods Institutional review board approval was obtained for this study; all patients gave written informed consent. ADCs were measured by two radiologists using three circular ROIs (three-ROIs), single-section (SS), and whole-tumor volume (WTV) methods in 62 patients with locally advanced rectal cancer on pre- and post-CRT images. Interobserver variability was analyzed by calculating intraclass correlation coefficient (ICC). Descriptive statistics and areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate performance in determining CR from pre- and post-CRT ADCs and ADC change. Histopathologic tumor regression grade was the reference standard. Results SS and WTV methods yielded higher AUCs than did the three-ROIs method when determining CR from post-CRT ADC (0.874 [95% confidence interval {CI}: 0.778, 0.970] and 0.886 [95% CI: 0.781, 0.990] vs 0.731 [95% CI: 0.583, 0.878], respectively; P = .033 and P = .003) and numeric change (0.892 [95% CI: 0.812, 0.972] and 0.897 [95% CI: 0.801, 0.994] vs 0.740 [95% CI: 0.591, 0.890], respectively; P = .048 and P = .0021). Respective accuracies of SS, WTV, and three-ROIs methods were 79% (49 of 62), 77% (48 of 62), and 61% (38 of 62) for post-CRT, 79% (49 of 62), 86% (53 of 62), and 60% (37 of 62) for numeric ADC change, and 77% (48 of 62), 84% (52 of 62), and 57% (35 of 62) for percentage ADC change (ADC cut-offs: 1.21, 1.30, and 1.05 * 10-3 mm2/sec, 0.33, 0.45, and 0.27 * 10-3 mm2/sec increases, and 40%, 54%, and 27% increases, respectively). Post-CRT and ADC change measurements achieved negative predictive values of 96% (44 of 46) to 100% (39 of 39). Intraobserver agreement was highest for WTV-derived ADCs (ICC, 0.742 [95% CI: 0.316, 0.892] to 0.891 [95% CI: 0.615, 0.956]) and higher for all pretreatment than posttreatment measurements (ICC, 0.761 [95% CI: 0.209, 0.930] and 0.648 [95% CI: 0.164, 0.895] for three-ROIs method, 0.608 [95% CI: 0.287, 0.844] and 0.582 [95% CI: 0.176, 0.870] for SS method, 0.891 [95% CI: 0.615, 0.956] and 0.742 for WTV method [95% CI: 0.316, 0.892]). Conclusion Tumor ADCs are highly dependent on the ROI positioning method used. Larger area measurements yield greater accuracy in response assessment. Post-CRT ADCs and values of ADC changes accurately identify noncomplete responders. WTV measurement of percentage ADC change provides the best results. (c) RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on September 19, 2016. PMID- 27253425 TI - Eosinophilic gastroenteritis: A state-of-the-art review. AB - Eosinophilic gastrointestinal disorders are a series of diseases that include eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. Among these disorders, eosinophilic gastroenteritis is an uncommon and heterogeneous disease characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of secondary causes, presenting with a variety of gastrointestinal manifestations. Up to now, epidemiology and pathophysiology of eosinophilic gastroenteritis are still unclear. Based on clinical manifestations and depth of eosinophilic infiltration into the gastrointestinal tract wall, eosinophilic gastroenteritis is classified into three different patterns including predominantly mucosal pattern, predominantly muscular pattern, and predominantly serosal pattern. For diagnosing eosinophilic gastroenteritis, it is necessary for clinicians to have a high degree of clinical suspicion. In addition to the gastrointestinal symptoms, other evidences such as laboratory results, radiological findings and endoscopy can also provide important diagnostic evidences for eosinophilic gastroenteritis. And these indirect pieces of information together with histological results will lead to a definitive diagnosis of eosinophilic gastroenteritis. To avoid specific allergen, dietary treatments can be considered as initial treatment strategy before drug treatment. Corticosteroids are the main medication for eosinophilic gastroenteritis and have a dramatic therapeutic efficacy. Yet other medications need to further verify their effects in clinical practice, and surgery should be avoided as far as possible. PMID- 27253426 TI - Psychometric properties of the Valued Living Questionnaire Adapted to Dementia Caregiving. AB - OBJECTIVES: Caring for a relative with dementia is associated with physical and emotional health problems in caregivers. There are no studies analysing the role of personal values in the caregiver stress process. This study aims to analyse the psychometric properties of the Valued Living Questionnaire Adapted to Caregiving (VLQAC), and to explore the relationship between personal values and stressors, coping strategies and caregiver distress. METHOD: A total of 253 individual interviews with caregivers of relatives with dementia were conducted, and the following variables were assessed: personal values, stressors, cognitive fusion, emotional acceptance, depression, anxiety, and satisfaction with life. An exploratory factor analysis and hierarchical regression analyses were carried out. RESULTS: Two factors were obtained, Commitment to Own Values and Commitment to Family Values which explain 43.42% of variance, with reliability coefficients (Cronbach's alpha) of .76 and .61, respectively. Personal values had a significant effect on emotional distress (depression and anxiety) and satisfaction with life, even when controlling for socio-demographic variables, stressors and coping strategies. CONCLUSION: Results suggest that the personal values construct of dementia caregivers is two-dimensional. The personal values of the caregivers play an important role in accounting for distress and satisfaction with life in this population. PMID- 27253427 TI - Perceived Control and Hedonic Tone Dynamics During Performance in Elite Shooters. AB - PURPOSE: The purpose of the study was to investigate the individuals' dynamics of perceived control and hedonic tone over time, with respect to the 4 performance states as conceptualized within the multiaction plan (MAP) model. We expected to find idiosyncratic and differentiated trends over time in the scores of perceived control and hedonic tone, typified by fluctuations among 2 optimal and 2 suboptimal types of processing during performance. METHOD: Ten elite-level shooters participated in the study. They were asked to identify the most relevant, idiosyncratic core component of their shooting action and perform 120 shots distanced 10 m from the target. Subjective accounts of perceived control and hedonic tone of the core component of action were assessed prior to and after each shot. We used a probabilistic approach to derive the 4 performance categories according to 2 * 2 interactions of perceived control and performance and hedonic tone and performance. RESULTS: Logistic ordinal regression analysis enabled the identification of 4 idiosyncratic performance types for each athlete with respect to perceived control and hedonic tone intensity scores. Within- and between-individual differences in intensity bandwidth and probability levels were apparent across the 4 performance types. Changes among 4 types of processing were also observed during performance. CONCLUSION: Consistent with the MAP model conceptualization, the findings provided support for the different patterns of perceived control and hedonic tone intensity scores during performance. The results suggest applied arguments for using action- and emotion-centered strategies to help athletes in reaching and sustaining optimal performance states. PMID- 27253428 TI - Automatic effects of illness schema activation on behavioral manifestations of illness. AB - OBJECTIVE: Relatively little research has directly evaluated the schematic nature of illness representations proposed by the common sense model of illness. Four studies tested the hypothesis that illness schema activation leads directly and automatically to behavioral manifestations of illness. METHOD: Study 1 was a survey (N = 970) that evaluated the proposition that the mental representation of common cold symptom experience includes functional deviation from the usual prototypical self. Studies 2 and 3 were experiments that tested effects of cold schema activation using a subliminal priming paradigm on walking speed (Study 2, N = 53) and free recall in a memory task (Study 3, N = 30). Study 4 (N = 65) used a 2 (cold prime vs. control) * 2 (alternate self vs. control) experimental design to investigate attenuation of the effect of the cold prime on free recall. RESULTS: Study 1 confirmed the multifactorial nature of functional self deviations representing the common cold symptomology. Studies 2 and 3 showed that participants primed with the common cold schema walked more slowly and performed worse on a memory recall task relative to controls in whom the schema was not activated. These effects were automatic in the sense that participants were not aware of the prime or of this influence. In Study 4, priming an alternative self identity overcame the deleterious effect of automatic common cold schema activation on free recall in a memory task. CONCLUSIONS: Subliminal activation of a schematic representation of illness automatically activates behavioral manifestations of illness. (PsycINFO Database Record PMID- 27253429 TI - Is daytime napping associated with inflammation in adolescents? AB - OBJECTIVE: Daytime napping has been associated with poor health outcomes in adults. It is not known whether daytime napping is similarly linked to adverse health in adolescents, although many report napping. The present study evaluated associations between daytime napping and 2 markers of increased inflammation, high-sensitivity C-reactive protein and interleukin-6 (IL-6), in healthy high school students. METHODS: Two hundred thirty-four Black and White high school students completed a week of actigraph and diary measures of sleep and napping and provided a fasting blood sample. Napping measures were the proportion of days napped and the average minutes napped across 1 week during the school year. RESULTS: Linear regressions adjusted for age, sex, race, average nocturnal sleep duration, time between sleep protocol and blood draw, and body mass index percentile demonstrated that proportion of days napped measured by actigraphy, B(SE) = .41(.19), p < .05, across the full week was positively associated with IL 6. Higher proportions of school days napped between 2 p.m. and 6 p.m., B(SE) = .40(.20), p < .05, and between 6 p.m. and 10 p.m., B(SE) = .57(.28), p < .05, were associated with increased IL-6. No associations emerged between average actigraphy-assessed nap duration and either study outcome. Diary-reported napping was unrelated to either study outcome. CONCLUSIONS: Actigraphy-assessed napping and IL-6 are associated but the direction of the relationship remains to be determined. Overall, napping is an important factor to consider to better understand the relationship between short sleep and cardiovascular health in adolescents. (PsycINFO Database Record PMID- 27253430 TI - In Vivo Self-Powered Wireless Cardiac Monitoring via Implantable Triboelectric Nanogenerator. AB - Harvesting biomechanical energy in vivo is an important route in obtaining sustainable electric energy for powering implantable medical devices. Here, we demonstrate an innovative implantable triboelectric nanogenerator (iTENG) for in vivo biomechanical energy harvesting. Driven by the heartbeat of adult swine, the output voltage and the corresponding current were improved by factors of 3.5 and 25, respectively, compared with the reported in vivo output performance of biomechanical energy conversion devices. In addition, the in vivo evaluation of the iTENG was demonstrated for over 72 h of implantation, during which the iTENG generated electricity continuously in the active animal. Due to its excellent in vivo performance, a self-powered wireless transmission system was fabricated for real-time wireless cardiac monitoring. Given its outstanding in vivo output and stability, iTENG can be applied not only to power implantable medical devices but also possibly to fabricate a self-powered, wireless healthcare monitoring system. PMID- 27253431 TI - MicroRNA-219-5p Inhibits Morphine-Induced Apoptosis by Targeting Key Cell Cycle Regulator WEE1. AB - BACKGROUND To identify the effects of microRNA (miR)-219-5p on morphine-induced apoptosis by targeting WEE1. MATERIAL AND METHODS Forty Balb/C mice (Toll-like receptor 9, TLR9 knockout) were randomly allocated to the experimental and control groups (20 in each group). The baseline miR-219-5p expression was detected using quantitative real-time PCR (qRT-PCR). After morphine was injected at 6 h on the 2nd and 6th days, experimental and control groups received miR-219 5p mimics or miRNA-negative control (NC), respectively, compound injection. Tissues and cells were later obtained from subjects in each group separately after mice were killed. TUNEL assay was used to investigate apoptosis in both groups. RAW264.7 cells were treated with miR-219-5p mimics and controls, respectively. After 24 h, 10 MUM of morphine was added at 24 h. Cell apoptosis was assessed by flow cytometer. The WEE1 and Phospho-cdc2 (Tyr15) expressions were examined by Western blotting. RESULTS MiR-219-5p expression in the experimental group was significantly lower than that in the control group (P<0.05). Mice injected with miR-219-5p mimic experienced an evident increase in apoptosis rate compared with the control group (P<0.05). The miR-219-5p NC group and the morphine group both presented an elevated apoptosis rate compared with the blank control group (both, P<0.05). The apoptosis rate in the miR-219-5p mimic group was 10.06%, remarkably lower than in the miR-219-5p NC group and blank control group (both P<0.05). WEE1 and Tyr15 protein expressions in the miR 219-5p NC group and morphine group were obviously stronger than those in the blank control group (all P<0.05). In the miR-219-5p mimic group, WEE1 and Tyr15 protein expressions were significantly lower compared with those in the miR-219 5p NC group and morphine group (all P<0.05). CONCLUSIONS Morphine significantly downregulated the expression of miRNA-219-5p, which targets WEE1 to suppress Tyr15 expressions and activate Cdc2, thus inhibiting the morphine-induced macrophage apoptosis. PMID- 27253432 TI - Zika Virus, Microcephaly, and Ocular Findings-Reply. PMID- 27253433 TI - Effect of Electrode Belt and Body Positions on Regional Pulmonary Ventilation- and Perfusion-Related Impedance Changes Measured by Electric Impedance Tomography. AB - Ventilator-induced or ventilator-associated lung injury (VILI/VALI) is common and there is an increasing demand for a tool that can optimize ventilator settings. Electrical impedance tomography (EIT) can detect changes in impedance caused by pulmonary ventilation and perfusion, but the effect of changes in the position of the body and in the placing of the electrode belt on the impedance signal have not to our knowledge been thoroughly evaluated. We therefore studied ventilation related and perfusion-related changes in impedance during spontaneous breathing in 10 healthy subjects in five different body positions and with the electrode belt placed at three different thoracic positions using a 32-electrode EIT system. We found differences between regions of interest that could be attributed to changes in the position of the body, and differences in impedance amplitudes when the position of the electrode belt was changed. Ventilation-related changes in impedance could therefore be related to changes in the position of both the body and the electrode belt. Perfusion-related changes in impedance were probably related to the interference of major vessels. While these findings give us some insight into the sources of variation in impedance signals as a result of changes in the positions of both the body and the electrode belt, further studies on the origin of the perfusion-related impedance signal are needed to improve EIT further as a tool for the monitoring of pulmonary ventilation and perfusion. PMID- 27253434 TI - Optical and Physicochemical Properties of Brown Carbon Aerosol: Light Scattering, FTIR Extinction Spectroscopy, and Hygroscopic Growth. AB - A great deal of attention has been paid to brown carbon aerosol in the troposphere because it can both scatter and absorb solar radiation, thus affecting the Earth's climate. However, knowledge of the optical and chemical properties of brown carbon aerosol is still limited. In this study, we have investigated different aspects of the optical properties of brown carbon aerosol that have not been previously explored. These properties include extinction spectroscopy in the mid-infrared region and light scattering at two different visible wavelengths, 532 and 402 nm. A proxy for atmospheric brown carbon aerosol was formed from the aqueous reaction of ammonium sulfate with methylglyoxal. The different optical properties were measured as a function of reaction time for a period of up to 19 days. UV/vis absorption experiments of bulk solutions showed that the optical absorption of aqueous brown carbon solution significantly increases as a function of reaction time in the spectral range from 200 to 700 nm. The analysis of the light scattering data, however, showed no significant differences between ammonium sulfate and brown carbon aerosol particles in the measured scattering phase functions, linear polarization profiles, or the derived real parts of the refractive indices at either 532 or 402 nm, even for the longest reaction times with greatest visible extinction. The light scattering experiments are relatively insensitive to the imaginary part of the refractive index, and it was only possible to place an upper limit of k <= 0.01 on the imaginary index values. These results suggest that after the reaction with methylglyoxal the single scattering albedo of ammonium sulfate aerosol is significantly reduced but that the light scattering properties including the scattering asymmetry parameter, which is a measure of the relative amount of forward-to-backward scattering, remain essentially unchanged from that of unprocessed ammonium sulfate. The optical extinction properties in the mid-IR range (800 to 7000 cm(-1)) also showed no significant changes in either the real or the imaginary parts of the refractive indices for brown carbon aerosol particles when compared to ammonium sulfate. Therefore, changes in the optical properties of ammonium sulfate in the mid-IR spectral range due to reaction with methylglyoxal appear to be insignificant. In addition to these measurements, we have characterized additional physicochemical properties of the brown carbon aerosol particles including hygroscopic growth using a tandem-differential mobility analyzer. Compared to ammonium sulfate, brown carbon aerosol particles are found to have lower deliquescence relative humidity (DRH), efflorescence relative humidity (ERH), and hygroscopic growth at the same relative humidities. Overall, our study provides new details of the optical and physicochemical properties of a class of secondary organic aerosol which may have important implications for atmospheric chemistry and climate. PMID- 27253435 TI - Changes in Policy Maker Attitudes Toward Active Living Communities Issues in Hawaii, 2007-2013. AB - BACKGROUND: Obesity and lack of physical activity are major public health problems in the United States. Well-designed, active living communities (ALCs) can help support physically active lifestyles. This study assessed attitudes of Hawaii decision makers in 2007 and 2013 to determine if priorities toward ALCs changed. METHODS: Elected and appointed state and county officials were mailed surveys both years. Respondents rated the importance of 23 specified problems, which included 1 obesity variable and 5 ALC variables. RESULTS: The survey was completed by 126 (70.4%) respondents in 2007 and 117 (60.9%) in 2013. Among the specific problems, only obesity increased in rank from 14th to ninth place. Three variables fell more than 2 places: increasing traffic (fifth to seventh place), poorly planned development and sprawl (seventh to 11th place) and pedestrian safety (12th to 17th place). The other 2 stayed relatively the same: lack of pedestrian walkways, sidewalks, and crosswalks (16th to 15th place) and lack of recreational activities (22nd to 23rd place). CONCLUSIONS: Across years, obesity concerns have increased but do not appear to be tied to increases in concern for ALC variables. More education for policymakers on the link between obesity, physical activity, and the built environment is necessary. PMID- 27253437 TI - Allostery: An Overview of Its History, Concepts, Methods, and Applications. AB - The concept of allostery has evolved in the past century. In this Editorial, we briefly overview the history of allostery, from the pre-allostery nomenclature era starting with the Bohr effect (1904) to the birth of allostery by Monod and Jacob (1961). We describe the evolution of the allostery concept, from a conformational change in a two-state model (1965, 1966) to dynamic allostery in the ensemble model (1999); from multi-subunit (1965) proteins to all proteins (2004). We highlight the current available methods to study allostery and their applications in studies of conformational mechanisms, disease, and allosteric drug discovery. We outline the challenges and future directions that we foresee. Altogether, this Editorial narrates the history of this fundamental concept in the life sciences, its significance, methodologies to detect and predict it, and its application in a broad range of living systems. PMID- 27253438 TI - Blood parasites of penguins: a critical review. AB - Blood parasites are considered some of the most significant pathogens for the conservation of penguins, due to the considerable morbidity and mortality they have been shown to produce in captive and wild populations of these birds. Parasites known to occur in the blood of penguins include haemosporidian protozoans (Plasmodium, Leucocytozoon, Haemoproteus), piroplamid protozoans (Babesia), kinetoplastid protozoans (Trypanosoma), spirochete bacteria (Borrelia) and nematode microfilariae. This review provides a critical and comprehensive assessment of the current knowledge on these parasites, providing an overview of their biology, host and geographic distribution, epidemiology, pathology and implications for public health and conservation. PMID- 27253439 TI - Iron-modulated pseudocyst formation in Tritrichomonas foetus. AB - Iron is an essential element for the survival of trichomonads during host parasite interaction. The availability of this metal modulates several metabolic pathways of the parasites and regulates the expression of virulence factors such as adhesins and proteolytic enzymes. In this study, we investigated the effect of iron depletion on the morphology and life cycle of Tritrichomonas foetus. Scanning and transmission electron microscopy analyses revealed that depletion of iron from the culture medium (named TYM-DIP inducer medium) induces morphological transformation of typical pear-shaped trophozoites into spherical and non-motile pseudocysts. Remarkably, inoculation of pseudocysts into an iron-rich medium (standard TYM medium), or addition of FeSO4 to a TYM-DIP inducer medium reverted the morphological transformation process and typical trophozoites were recovered. These results show that pseudocysts are viable forms of the parasite and highlight the role of iron as a modulator of the parasite phenotype. Although iron is required for the survival of T. foetus, iron depletion does not cause a cellular collapse of pseudocysts, but instead induces phenotypic alterations, probably in order to allow the parasite to survive conditions of nutritional stress. Together, these findings support previous studies that suggest pseudocysts are a resistance form in the life cycle of T. foetus and enable new approaches to understanding the multifactorial role of iron in the cell biology of this protozoan parasite. PMID- 27253436 TI - Selection for Protein Kinetic Stability Connects Denaturation Temperatures to Organismal Temperatures and Provides Clues to Archaean Life. AB - The relationship between the denaturation temperatures of proteins (Tm values) and the living temperatures of their host organisms (environmental temperatures: TENV values) is poorly understood. Since different proteins in the same organism may show widely different Tm's, no simple universal relationship between Tm and TENV should hold, other than Tm>=TENV. Yet, when analyzing a set of homologous proteins from different hosts, Tm's are oftentimes found to correlate with TENV's but this correlation is shifted upward on the Tm axis. Supporting this trend, we recently reported Tm's for resurrected Precambrian thioredoxins that mirror a proposed environmental cooling over long geological time, while remaining a shocking ~50 degrees C above the proposed ancestral ocean temperatures. Here, we show that natural selection for protein kinetic stability (denaturation rate) can produce a Tm<->TENV correlation with a large upward shift in Tm. A model for protein stability evolution suggests a link between the Tm shift and the in vivo lifetime of a protein and, more specifically, allows us to estimate ancestral environmental temperatures from experimental denaturation rates for resurrected Precambrian thioredoxins. The TENV values thus obtained match the proposed ancestral ocean cooling, support comparatively high Archaean temperatures, and are consistent with a recent proposal for the environmental temperature (above 75 degrees C) that hosted the last universal common ancestor. More generally, this work provides a framework for understanding how features of protein stability reflect the environmental temperatures of the host organisms. PMID- 27253441 TI - The Added Value of Family Material in the Discovery of Multiple Sclerosis Genes. AB - A mutation in a nuclear receptor (NR1H3) gene was detected in a familial, progressive form of multiple sclerosis (PPMS). Further analyses showed a significant association between a common NR1H3 variant in PPMS patients and loss of function for the encoded protein. PMID- 27253440 TI - Fetal alcohol spectrum disorders and assessment of maxillary and mandibular arc measurements. AB - Fetal alcohol spectrum disorders (FASD) comprise a range of physical differences and neurologic deficits from prenatal alcohol exposure. Previous studies suggest that relative maxillary growth deficiency can accompany FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how maxillary and mandibular arcs and the ratio between them differ between FASD and non-FASD individuals. First, we established normative values for maxillary and mandibular arcs and maxillary-to-mandibular arc ratio. In our control group (545 males, 436 females), mean maxillary and mandibular arcs for males/females were 24.98/24.52 cm and 25.91/25.35 cm, respectively. The ratio was 0.9643 and 0.9676 for males and females, respectively. We then evaluated the effect of microcephaly, short stature, and low weight (<10th centile), individually on arcs in controls. Generally, arcs were reduced significantly but the ratio did not differ. We compared our controls to 138 male and 135 female FASD cases. We noted a significant difference in arcs in male and female groups, but not the ratio. We compared non-FAS controls with reduced growth parameters to similar cases with FASD. We did not find a significant difference in arc or ratio measurements. Therefore, we conclude the effect of prenatal alcohol exposure on maxillary and mandibular arc measurements is primarily on overall facial growth and less on asymmetric growth of the maxilla relative to the mandible, at least using this technique. (c) 2016 Wiley Periodicals, Inc. PMID- 27253442 TI - Dynein's Life in the Slow Lane. AB - Dynein synthesized in neuronal cell bodies is conveyed into the axon by slow transport, but underlying mechanisms are unclear. In this issue, Twelvetrees et al. (2016) propose a model where dynein is transported by direct-but transient interactions with kinesin. PMID- 27253443 TI - Melanopsin: The Tale of the Tail. AB - In this issue of Neuron, Mure et al. (2016) demonstrate that two mechanisms phosphorylation of a C-terminal intracellular region, and mechanism involving the whole of the C terminus-oppositely shape the kinetics and sensitivity of the nonvisual photoreceptor melanopsin. PMID- 27253444 TI - The Variable Strength of Electrical Synapses. AB - In contrast to chemical synapses, less is known regarding the determinants of the strength of electrical synapses. New evidence from Szoboszlay et al. (2016) shows that the number of gap junctions is the dominant factor underlying the strength of electrical coupling between cerebellar interneurons. PMID- 27253445 TI - Cholinergic Coercion of Synaptic States for Motivational Memories. AB - Acetylcholine is critical for learning, yet the relationship between cholinergic signaling, plasticity, and behavior remains elusive. In this issue of Neuron, Lee et al. (2016) and Jiang et al. (2016) investigate how cholinergic signaling in the amygdala and nucleus accumbens influences synaptic plasticity and learning. PMID- 27253446 TI - Neuroscience Training for the 21st Century. AB - The field of neuroscience is enjoying a rapid expansion in scope, coupled with a remarkable broadening of conceptual approaches, scientific tools, and clinical applications. This growth poses new challenges for academic training programs as they prepare young neuroscientists for a more complex, competitive, and diverse career landscape. Multiple stakeholders, including academia, federal funding agencies, industry, scientific societies, private foundations, and other public and private sector contributors, need to be actively engaged in supporting this broad training effort. A renewed commitment to a more forward-looking, flexible yet integrative training vision offers opportunities for a bright future for young neuroscientists as they assume the role of vanguard of the enterprise that enriches our understanding of the brain. PMID- 27253447 TI - Decision Making and Sequential Sampling from Memory. AB - Decisions take time, and as a rule more difficult decisions take more time. But this only raises the question of what consumes the time. For decisions informed by a sequence of samples of evidence, the answer is straightforward: more samples are available with more time. Indeed, the speed and accuracy of such decisions are explained by the accumulation of evidence to a threshold or bound. However, the same framework seems to apply to decisions that are not obviously informed by sequences of evidence samples. Here, we proffer the hypothesis that the sequential character of such tasks involves retrieval of evidence from memory. We explore this hypothesis by focusing on value-based decisions and argue that mnemonic processes can account for regularities in choice and decision time. We speculate on the neural mechanisms that link sampling of evidence from memory to circuits that represent the accumulated evidence bearing on a choice. We propose that memory processes may contribute to a wider class of decisions that conform to the regularities of choice-reaction time predicted by the sequential sampling framework. PMID- 27253449 TI - M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia. PMID- 27253448 TI - Nuclear Receptor NR1H3 in Familial Multiple Sclerosis. AB - Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss and neuronal dysfunction. Despite the aggregation observed in some families, pathogenic mutations have remained elusive. In this study, we describe the identification of NR1H3 p.Arg415Gln in seven MS patients from two multi-incident families presenting severe and progressive disease, with an average age at onset of 34 years. Additionally, association analysis of common variants in NR1H3 identified rs2279238 conferring a 1.35-fold increased risk of developing progressive MS. The p.Arg415Gln position is highly conserved in orthologs and paralogs, and disrupts NR1H3 heterodimerization and transcriptional activation of target genes. Protein expression analysis revealed that mutant NR1H3 (LXRA) alters gene expression profiles, suggesting a disruption in transcriptional regulation as one of the mechanisms underlying MS pathogenesis. Our study indicates that pharmacological activation of LXRA or its targets may lead to effective treatments for the highly debilitating and currently untreatable progressive phase of MS. PMID- 27253450 TI - High Expression of HULC Is Associated with Poor Prognosis in Osteosarcoma Patients. AB - Osteosarcoma (OS) is the most common primary bone cancer in childhood. OS is an aggressive disease, and metastatic patients evolve with very poor clinical outcomes. Genetically, OSs are extremely complex tumors, and the related metastatic process is not well understood in terms of the biology of the disease. In this context, long non-coding RNAs (lncRNAs) have emerged as an important class of gene expression regulators that play key roles in the invasion and metastasis of several human tumors. Here, we evaluated the expression of HULC, which is an lncRNA that is associated with the tumor metastatic process, and assessed its potential role as a prognostic marker in OS. HULC expression was evaluated in primary OS samples using real-time RT-PCR. HULC expression status was determined by receiver operating characteristic (ROC) analysis, and its association with survival was assessed using the Kaplan-Meier method. The HULC expression level was not significantly associated with the clinicopathological characteristics of the OS patients. However, our data demonstrated that higher levels of expression of HULC were associated with lower survival rates in OS patients, both in terms of overall and event-free survival. Elevated HULC expression was associated with poor clinical outcomes among the OS patients, which suggests that HULC could be a potential prognostic biomarker in OS. PMID- 27253451 TI - Erythrocyte intracellular Mg(2+) concentration as an index of recognition and memory. AB - Magnesium (Mg(2+)) plays an important role in the neural system, and yet scarcely any research has quantitatively analyzed the link between endogenous Mg(2+) level and memory. Using our original technique, we measured erythrocyte intracellular ionized Mg(2+) concentration (RBC [Mg(2+)]i), which linearly correlated to recognition and spatial memory in normal aging rats. In the brain, RBC [Mg(2+)]i significantly correlated to hippocampus extracellular fluid Mg(2+) concentration, and further correlated to hippocampal synapse density. Elevation of Mg(2+) intake in aged rats demonstrated an association between RBC [Mg(2+)]i increase and memory recovery. The therapeutic effect of Mg(2+) administration was inversely correlated to individual basal RBC [Mg(2+)]i. In summary, we provide a method to measure RBC [Mg(2+)]i, an ideal indicator of body Mg(2+) level. RBC [Mg(2+)]i represents rodent memory performance in our study, and might further serve as a potential biomarker for clinical differential diagnosis and precise treatment of Mg(2+)-deficiency-associated memory decline during aging. PMID- 27253452 TI - The visual development of hand-centered receptive fields in a neural network model of the primate visual system trained with experimentally recorded human gaze changes. AB - Neurons have been found in the primate brain that respond to objects in specific locations in hand-centered coordinates. A key theoretical challenge is to explain how such hand-centered neuronal responses may develop through visual experience. In this paper we show how hand-centered visual receptive fields can develop using an artificial neural network model, VisNet, of the primate visual system when driven by gaze changes recorded from human test subjects as they completed a jigsaw. A camera mounted on the head captured images of the hand and jigsaw, while eye movements were recorded using an eye-tracking device. This combination of data allowed us to reconstruct the retinal images seen as humans undertook the jigsaw task. These retinal images were then fed into the neural network model during self-organization of its synaptic connectivity using a biologically plausible trace learning rule. A trace learning mechanism encourages neurons in the model to learn to respond to input images that tend to occur in close temporal proximity. In the data recorded from human subjects, we found that the participant's gaze often shifted through a sequence of locations around a fixed spatial configuration of the hand and one of the jigsaw pieces. In this case, trace learning should bind these retinal images together onto the same subset of output neurons. The simulation results consequently confirmed that some cells learned to respond selectively to the hand and a jigsaw piece in a fixed spatial configuration across different retinal views. PMID- 27253453 TI - Oxygen Nanocarrier for Combined Cancer Therapy: Oxygen-Boosted ATP-Responsive Chemotherapy with Amplified ROS Lethality. AB - Oxygen nanocarrier (A/D-ONC) with a polymeric core entrapping hemoglobin and a cationic lipid shell absorbing a DOX-intercalating DNA duplex is developed. After endocytosis oxygenated A/D-ONC donates O2 to cancer cells that acts therapeutically by: (1) increasing intracellular ATP content that promotes DOX release, thereby converting ATP to the trigger of detrimental chemotherapy; (2) by synchronously increasing the ROS amount to amplify the lethality to cancer cells. PMID- 27253455 TI - [Use of private motor vehicle transportation for taking children to school in Sao Paulo Metropolitan Area, Brazil, 1997-2012]. AB - Sao Paulo Metropolitan Area, Brazil, showed an increase from 1997 to 2007 in the use of private motor vehicles for taking children to school, with potential harm to their health. The aim of this study was to extend the analysis of this trend until 2012 and discuss possible strategies to increase the proportion of children who walk, cycle, or use public transportation to get to school. Analysis of the data from the Mobility Survey of 2012 indicate not only the continuation but also an accelerated increase in the use of private motorized transportation for schoolchildren aged 6 to 11 years. The effect of initiatives to promote walking will only be properly understood with adequate monitoring of daily commuting to school and the evaluation of their impact on the population's health. A package of policies and programs specifically targeted to the promotion and protection of walking, cycling, and use of public transport by schoolchildren is indispensable for guaranteeing their right to travel safely, independently, and actively in Sao Paulo Metropolitan Area. PMID- 27253454 TI - Patent foramen ovale in adults with sickle cell disease and stroke. PMID- 27253456 TI - [Why reconsider the recommendation of breast cancer screening?]. AB - The aim of this article was to discuss the recommendation of mammogram screening for breast cancer and its technical basis. The first part discusses criteria for the decision, which should be consistent with high-quality scientific evidence. The second part discusses over-diagnosis (the greatest harm of screening) and its meaning in questioning the natural history of disease model. The third part summarizes studies on the efficacy, effectiveness, and harms of screening, showing that the latter (especially over-diagnosis and false-positives) are significant, shedding doubt on the balance between harms and benefits. In conclusion, the recommendation of mammogram screening at any age should be reconsidered by Brazilian health authorities. PMID- 27253457 TI - [Not Available]. PMID- 27253458 TI - Diabetes education in primary care: a randomized clinical trial. AB - The aim of the study was to evaluate the effect of a structured group education program administered by a primary care nurse in patients with type 2 diabetes mellitus. The sample included 137 patients with type 2 diabetes mellitus, randomized into two groups: intervention (5-week educational course and reinforcements every 4 months for one year) and control (with no structured diabetes mellitus education) with an evaluation of metabolic control, weight, blood pressure, distress scores, and knowledge on diabetes. There were no differences between the two groups in HbA1c at 4, 8, or 12 months when compared to baseline values. An increase in HbA1c was observed in the control group after adjusting for baseline HbA1c and insulin dose (p = 0.044 between groups). Knowledge scores and diabetes-related distress improved after the intervention. A structured educational program administered to type 2 diabetes mellitus patients seen at a primary care unit improved the knowledge and distress associated with the disease. The results also suggest the prevention of an increase in HbA1c. PMID- 27253459 TI - Incentives and barriers to HIV testing in men who have sex with men in a metropolitan area in Brazil. AB - This study aimed to identify incentives and barriers to HIV testing in men who have sex with men (MSM). This was a cross-sectional study of MSM who had lived at least three months in greater metropolitan Fortaleza, Ceara State, Brazil, 2010. The study recruited 391 men >= 18 years of age who reported sexual relations with men in the previous six months, using Respondent Driven Sampling. Personal network and socio-demographic data were collected and HIV testing was offered, analyzed with RDSAT 6.0 and Stata 11.0. The majority were young (40.3%), had 5 to 11 years of schooling (57.3%), were single (85.1%), had low income (37.6%), and 58.1% had tested for HIV some time in life. Incentive to test: certainty of not being infected (34.1%) and the exposure to national campaign Fique Sabendo [Know your Status] (34%). Barriers: trust in partner(s) (21%) and fear of discrimination if tested positive (20.3%). Policies should be developed to ensure test confidentiality and communication campaigns focusing on information gaps and encouragement for testing. PMID- 27253460 TI - [Not Available]. PMID- 27253462 TI - Solar Thermal Energy Storage in a Photochromic Macrocycle. AB - The conversion and efficient storage of solar energy is recognized to hold significant potential with regard to future energy solutions. Molecular solar thermal batteries based on photochromic systems exemplify one possible technology able to harness and apply this potential. Herein is described the synthesis of a macrocycle based on a dimer of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo/thermal couple. By taking advantage of conformational strain, this DHA-DHA macrocycle presents an improved ability to absorb and store incident light energy in chemical bonds (VHF-VHF). A stepwise energy release over two sequential ring closing reactions (VHF->DHA) combines the advantages of an initially fast discharge, hypothetically addressing immediate energy consumption needs, followed by a slow process for consistent, long-term use. This exemplifies another step forward in the molecular engineering and design of functional organic materials towards solar thermal energy storage and release. PMID- 27253461 TI - MGMT Promoter Methylation and BRAF V600E Mutations Are Helpful Markers to Discriminate Pleomorphic Xanthoastrocytoma from Giant Cell Glioblastoma. AB - Giant Cell Glioblastoma (gcGBM) and Pleomorphic Xanthoastrocytoma (PXA) are rare astroglial tumors of the central nervous system. Although they share certain histomorphological and immunohistochemical features, they are characterized by different clinical behavior and prognosis. Nevertheless, few cases remain uncertain, as their histomorphological hallmarks and immunophenotypes do correspond to the typical pattern neither of gcGBM nor PXA. Therefore, in addition to the routinely used diagnostic histochemical and immunohistochemical markers like Gomori, p53 and CD34, we analyzed if genetic variations like MGMT promoter methylation, mutations in the IDH1/2 genes, or BRAF mutations, which are actually used as diagnostic, prognostic and predictive molecular markers in anaplastic glial tumors, could be helpful in the differential diagnostic of both tumor entities. We analyzed 34 gcGBM and 20 PXA for genetic variations in the above-named genes and found distinct distributions between both groups. MGMT promoter hypermethylation was observed in 3 out of 20 PXA compared to 14 out of 34 gcGBM (15% vs. 41.2%, p-value 0.09). BRAF V600E mutations were detected in 50% of the PXA but not in any of the gcGBM (50% vs. 0%, p-value < 0.001). IDH1 R132 and IDH R172 mutations were not present in any of the PXA and gcGBM cases. Our data indicate, that in addition to the histological and immunohistochemical evaluation, investigation of MGMT promoter methylation and in particular BRAF V600E mutations represent reliable additional tools to sustain differentiation of gcGBM from PXA on a molecular basis. Based on these data specific BRAF kinase inhibitors could represent a promising agent in the therapy of PXA and their use should be emphasized. PMID- 27253463 TI - EZH2 suppresses the nucleotide excision repair in nasopharyngeal carcinoma by silencing XPA gene. AB - The enhancer of zeste homolog 2 (EZH2) is involved in a number of fundamental pathological processes of cancer. However, its role in DNA repair pathway is still unclear. Here, we have identified XPA as a novel target gene of EZH2 via a DNA repair pathway PCR array. XPA plays a pivot role in nucleotide excision repair (NER). The expression of XPA was significantly increased by EZH2 specific inhibitor GSK126 or lentiviral shEZH2 in nasopharyngeal carcinoma (NPC) CNE and 8F cell lines. Chromatin immunoprecipitation assay demonstrated that EZH2 catalyzes H3K27 trimethylation at the XPA promoters. Furthermore, we validated the negative correlation of EZH2 and XPA in a NPC tissue microarray by immunohistochemistry staining. We also found that high expression of EZH2 was positively correlated with advanced T, N, and AJCC stage of NPC; and low expression of XPA was positively correlated with advanced T and N stage. In NPC cell lines, increased XPA expression by EZH2 inhibition resulted in a more rapid removal of UVC induced 6-4PP- and CPD-DNA adducts, as well as enhanced efficiency of DNA repair after UVC irradiation as detected by the Comet assay and immunofluorescence staining of gammaH2Ax. Consistently, increased cell clonogenic survival, decreased apoptosis, and necrosis after UVC irradiation, and increased resistance to DNA damaging agent cisplatin was also observed in EZH2 inhibited cells. These results illustrate that EZH2 may promote carcinogenesis and cancer development of NPC by transcriptional repression of XPA gene and inactivation of NER pathway. (c) 2016 Wiley Periodicals, Inc. PMID- 27253464 TI - Cartilage-Specific and Cre-Dependent Nkx3.2 Overexpression In Vivo Causes Skeletal Dwarfism by Delaying Cartilage Hypertrophy. AB - Nkx3.2, the vertebrate homologue of Drosophila bagpipe, has been implicated as playing a role in chondrogenic differentiation. In brief, Nkx3.2 is initially expressed in chondrocyte precursor cells and later during cartilage maturation, its expression is diminished in hypertrophic chondrocytes. In addition to Nkx3.2 expression analyses, previous studies using ex vivo chick embryo cultures and in vitro cell cultures have suggested that Nkx3.2 can suppress chondrocyte hypertrophy. However, it has never been demonstrated that Nkx3.2 functions in regulating chondrocyte hypertrophy during cartilage development in vivo. Here, we show that cartilage-specific and Cre-dependent Nkx3.2 overexpression in mice results in significant postnatal dwarfism in endochondral skeletons, while intramembranous bones remain unaltered. Further, we observed significant delays in cartilage hypertrophy in conditional transgenic ciTg-Nkx3.2 mice. Together, these findings confirm that Nkx3.2 is capable of controlling hypertrophic maturation of cartilage in vivo, and this regulation plays a significant role in endochondral ossification and longitudinal bone growth. J. Cell. Physiol. 232: 78 90, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27253465 TI - Can Nonvalidated Lower GI Bleeding Predictive Scores be Evaluated by Receiver Operator Characteristics? PMID- 27253466 TI - Novel Indications for Surgical Resection of Metachronous Lung Metastases From Pancreatic Cancer After Curative Resection. AB - Few reports exist regarding surgical resection of metachronous lung metastases (MLM) from pancreatic ductal adenocarcinoma (PDA) after curative resection. To elucidate the indications for surgical resection of MLM and long-term survival, we analyzed Japanese case reports of MLM from PDA. Between 1983 and 2014, 17 Japanese case reports concerning surgical resection of MLM from PDA were published. We determined long-term survival in 16 patients (considering the published data of 15 patients and 1 of our own) by using a questionnaire survey and analyzing the relationships between background factors and long-term survival. In 16 patients with long-term survival, 4 patients were still alive without recurrence. The remaining 12 patients died of disease after recurrence. The median survival after the initial lobectomy was 37 months and the 3- and 5 year survival for all patients after lobectomy was 50% and 41%, respectively. Fourteen patients had a disease-free interval after initial resection of the primary pancreatic tumor of >20 months. These patients had a longer median survival period after lobectomy (46 vs. 25.5 mo, P=0.19). Seven patients had MLM of <16 mm. These patients had a statistically longer overall survival after lobectomy (83 vs. 16 mo, P=0.04). Three of 4 patients with primary stage I tumors were still alive without recurrence. We found that the conventional criteria for surgical resection of MLM from PDA (first disease-free interval of >20 mo with no other metastatic lesions) were appropriate. In addition, it is possible that MLM of <16 mm or primary stage I tumors are novel criteria. PMID- 27253475 TI - Why were alternating-current-driven electrochemiluminescence properties from Ru(bpy)3(2+) dramatically improved by the addition of titanium dioxide nanoparticles? AB - Electrochemiluminescence (ECL) is a phenomenon in which light is emitted from the excited state of a redox-active material generated by electrochemical reactions. Among light-emitting devices, ECL devices have various advantages in terms of structure and ease of fabrication, and therefore, they are expected to be next generation emitting devices. In this study, we introduced rutile-type titanium dioxide nanoparticles (TiO2 NPs) in a Ru(ii)-complex-based electrolyte to improve the emission properties of an alternating current (AC)-driven ECL device. The properties of the ECL device with TiO2 NPs were greatly improved (emission luminescence, 165 cd m(-2); half-life time, 1000 s) compared to a previously reported AC-driven ECL device without nanoparticles. To determine how TiO2 NPs helped in achieving high emission luminescence and long-term stability, we measured the optical and electrochemical properties of the Ru(bpy)3(2+)-based ECL solution in detail. The PL intensity of Ru(bpy)3(2+) was increased by adding TiO2 NPs, which indicated that the suppression of non-radiative quenching of the complex's excited states could improve the ECL intensity. With respect to the enhanced stability, electron transfers between Ru(bpy)3(2+) and TiO2 were suggested by detailed electrochemical measurements. These electron transfers occurred from the reduced Ru(bpy)3(2+) species to the TiO2, and subsequently, from the TiO2 to the oxidized Ru(bpy)3(2+) species. Such electron transfers are thought to improve the balance of the redox reactions in the ECL device, leading to long-term stability. PMID- 27253476 TI - Sustainable hydrogen production from bio-oil model compounds (meta-xylene) and mixtures (1-butanol, meta-xylene and furfural). AB - In the present work m-xylene and an equimolecular mixture of m-xylene, 1-butanol and furfural, all of them bio-oil model compounds, were studied in steam reforming (SR) conditions. Three different nickel catalysts, which showed to be active in 1-butanol SR (Ni/Al2O3, Ni/CeO2-Al2O3 and Ni/La2O3-Al2O3), were tested and compared with thermodynamic equilibrium values. Tests were carried out at temperatures from 800 to 600 degrees C at atmospheric pressure with a steam to carbon ratio (S/C) of 5.0. Despite the different bio-oils fed, the amount of moles going through the catalytic bed was kept constant in order to obtain comparable results. After their use, catalysts were characterized by different techniques and those values were correlated with the activity results. All catalysts were deactivated during the SR of the mixture, mainly by coking. The highest hydrogen yields were obtained with Ni/Al2O3 and Ni/CeO2-Al2O3 catalysts in the SR of m-xylene and SR of the mixture, respectively. PMID- 27253477 TI - Accelerated acidification by inoculation with a microbial consortia in a complex open environment. AB - Bioaugmentation using microbial consortia is helpful in some anaerobic digestion (AD) systems, but accelerated acidification to produce methane has not been performed effectively with corn stalks and cow dung. In this study, the thermophilic microbial consortia MC1 was inoculated into a complex open environment (unsterilized and sterilized systems) to evaluate the feasibility of bioaugmentation to improve acidification efficiency. The results indicated that MC1 itself degraded lignocellulose efficiently, and accumulated more organic acids within 3days. Similar trends were also observed in the unsterilized system, where the hemicellulose degradation rate and organic acid concentrations increased significantly by two-fold and 20.1% (P<0.05), respectively, and clearly reduced the loss of product. Microbial composition did not change obviously after inoculating MC1, but the abundance of members of MC1, such as Bacillus and Clostridium, increased clearly on day 3. Finally, the acidogenic fluid improved methane yield significantly (P<0.05) via bioaugmentation. PMID- 27253478 TI - Valorization of Rhizoclonium sp. algae via pyrolysis and catalytic pyrolysis. AB - The valorization of Rhizoclonium sp. algae through pyrolysis for obtaining bio oils is studied in this work. The reaction is carried out at 400 degrees C, at high contact time. The bio-oil has a practical yield of 35% and is rich in phytol. Besides, it is simpler than the corresponding to lignocellulosic biomass due to the absence of phenolic compounds. This property leads to a bio-oil relatively stable to storage. In addition, heterogeneous catalysts (Al-Fe/MCM-41, SBA-15 and Cu/SBA-15), in contact with algae during pyrolysis, are analyzed. The general trend is that the catalysts decrease the concentration of fatty alcohols and other high molecular weight products, since their mild acidity sites promote degradation reactions. Thus, the amount of light products increases upon the use of the catalysts. Particularly, acetol concentration in the bio-oils obtained from the catalytic pyrolysis with SBA-15 and Cu/SBA-15 is notably high. PMID- 27253479 TI - New Delhi metallo-beta-lactamase-1: structure, inhibitors and detection of producers. AB - Since its discovery in 2008, New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Enterobacteriaceae have disseminated globally, facilitated predominantly by gut colonization and the spread of plasmids carrying the bla NDM-1 gene. With few effective antibiotics against NDM-1 producers, and resistance developing to those which remain, there is an urgent need to develop new treatments. To date, most drug design in this area has been focused on developing an NDM-1 inhibitor and has been aided by the wealth of structural and mechanistic information available from high resolution x-ray crystallography and molecular modeling. This review aims to summarize current knowledge regarding the detection of NDM-1 producers, the mechanism of action of NDM-1 and to highlight recent attempts toward the development of clinically useful inhibitors. PMID- 27253480 TI - Photochemistry of rose bengal in water and acetonitrile: a comprehensive kinetic analysis. AB - The photophysical and photochemical properties of rose bengal (RB) in degassed aqueous and acetonitrile solutions were studied using steady-state and transient absorption spectroscopies. This comprehensive investigation provides detailed information about the kinetics and the optical properties of all intermediates involved: the triplet excited state and the oxidized and reduced forms of RB. A full kinetic description is used to control the concentrations of these intermediates by changing the initial experimental conditions. PMID- 27253481 TI - Prospective Evaluation of Posttraumatic Stress Disorder in Injured Patients With and Without Orthopaedic Injury. AB - OBJECTIVES: The study purposes were to prospectively evaluate occurrence of posttraumatic stress (PTS) symptoms at hospital admission and 6 months later in patients with orthopaedic injury; to explore differences in PTS symptoms in those with and without orthopaedic injury; and to determine whether PTS symptoms are influenced by orthopaedic injury type. DESIGN: Prospective, longitudinal observational study. SETTING: Level 1 Trauma Center. PATIENTS/PARTICIPANTS: Two hundred fifty-nine participants admitted for at least 24 hours. MAIN OUTCOME MEASUREMENTS: The Primary Care Posttraumatic Stress Disorder (PTSD) Screen (PC PTSD) measured PTSD symptoms during hospitalization. The PTSD Checklist-Civilian Version (PCL-C) measured PTS symptoms at 6 months. RESULTS: In orthopaedic patients, 28% had PTS at 6 months, compared with 34% of nonorthopaedic patients. Odds ratios (ORs) were calculated to determine the influence of pain, physical and mental function, depression, and work status. At 6 months, if the pain score was 5 or higher, the odds of PTS symptoms increased to 8.38 (3.55, 19.8) (P < 0.0001). Those scoring below average in physical function were significantly more likely to have PTS symptoms [OR = 7.60 (2.99, 19.32), P < 0.0001]. The same held true for mental functioning and PTS [OR = 11.4 (4.16, 30.9), P < 0.0001]. Participants who screened positive for depression had a 38.9 (14.5, 104) greater odds (P < 0.0001). Participants who did not return to work after injury at 6 months were significantly more likely to have PTS [OR = 16.5 (1.87, 146), P = 0.012]. CONCLUSIONS: PTSD is common in patients after injury, including those with orthopaedic trauma. At 6 months, pain of 5 or greater, poor physical and mental function, depression, and/or not returning to work seem to be predictive of PTSD. Orthopaedic surgeons should identify and refer for PTSD treatment given the high incidence postinjury. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence. PMID- 27253482 TI - Do 25-Hydroxyvitamin D Levels Correlate With Fracture Complications? AB - OBJECTIVES: To determine the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the likelihood of postoperative complications and fracture reoperation rate in orthopaedic trauma patients receiving vitamin D and calcium supplementation. DESIGN: Retrospective case series. SETTING: Level I trauma center, Midwestern United States. PATIENTS: All orthopaedic trauma patients-18 years or older-over a 20-month period were included with available initial and repeat 25(OH)D serum levels. In total, 201 patients met inclusion criteria. INTERVENTION: All patients received 1000 IU of vitamin D3 and 1500 mg of calcium daily. Vitamin D deficient and insufficient patients also received 50,000 IU of ergocalciferol (vitamin D2) weekly until 25(OH)D levels normalized or fractures healed. MAIN OUTCOME MEASUREMENTS: fracture complications and 25(OH)D levels. RESULTS: Fifteen patients experienced postoperative healing complications. There was no significant difference between initial (P = 0.92) or repeat (P = 0.91) 25(OH)D levels between patients with and without fracture healing complications. Twenty-eight patients required repeat orthopaedic surgery. There was no significant difference between initial (P = 0.62) or repeat (P = 0.18) 25(OH)D levels between patients who did or did not require repeat orthopaedic surgery. There was no significant difference between initial (P = 0.66) or repeat (P = 0.89) 25(OH)D levels between patients who did or did not require nonorthopaedic surgery. CONCLUSIONS: Serum 25(OH)D levels did not significantly affect the likelihood of fracture healing complications requiring surgery or any nonorthopaedic injury-related surgery. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 27253483 TI - Molecular characterization of hepatitis B virus in blood donors from Burkina Faso: Prevalence of quasi-subgenotype A3, genotype E, and mixed infections. AB - Burkina Faso is a highly endemic area for Hepatitis B virus (HBV) which remains a major challenge for blood safety with >13% of candidate blood donors being chronically infected. However, little is known about the molecular epidemiology of the viral strains currently circulating. In this study, 99 HBV strains from HBsAg positive candidate blood donors in Ougadougou were genetically characterized by sequencing the pre-S/S region of the viral genome. Phylogenetic analyses revealed a 25% prevalence of HBV quasi-subgenotype A3 (A3QS ) co circulating with the confirmed dominant HBV genotype E (72%). HBV/A3QS sequences formed a sub-cluster closely related to West-African sequences previously characterized, and showed a low intra-group genetic diversity (0.75%) suggesting a relatively recent spreading of HBV/A3QS strains in Burkina Faso. Low genetic diversity of genotype E strains compared to A3QS was confirmed. Mixed infections with the two genotypes were identified in 3% of the donors tested and contributed to artifacts during PCR amplification of the viral genome leading to erroneous apparent intergenotype recombinant sequences. While the co-circulation of two HBV genotypes in a restricted area may favor the emergence of intergenotype recombinant variants, strictly controlled molecular experimental procedures should be used to accurately characterize HBV circulating recombinant forms. J. Med. Virol. 88:2145-2156, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27253484 TI - Update on biphasic anaphylaxis. AB - PURPOSE OF REVIEW: Biphasic anaphylaxis is a well documented complication of anaphylaxis, but it has been inconsistently defined in the literature. Analysis of contemporary studies of biphasic anaphylaxis based on modern definitions is needed. RECENT FINDINGS: The rate of biphasic reactions in contemporary literature ranges from 0.4 to 14.7% depending on the study population. Observational studies have reported risk factors associated with the development of biphasic reactions; however, findings have been inconsistent and of questionable generalizability. Although life-threatening biphasic reactions are rare, up to 50% of biphasic reactions will require treatment with epinephrine. Early epinephrine administration may have a role in prevention of biphasic reactions, but the role of steroids needs further investigation. The optimal duration of observation is yet to be determined. SUMMARY: Given the relative rarity of life-threatening biphasic anaphylaxis and the new context of the NIAID/FAAN standardized definition, further research regarding biphasic anaphylaxis is needed to better elucidate the care model for anaphylaxis patients with a focus on: prevention of biphasic reactions; identification of patients at increased risk of a biphasic reaction; determination of appropriate observation strategies for anaphylaxis patients; and patient education and preparation for management of potential biphasic reactions. PMID- 27253485 TI - Management of rhinosinusitis: an evidence based approach. AB - PURPOSE OF REVIEW: The most recent recommendations for the management of both acute (ARS) and chronic rhinosinusitis (CRS) based on the strongest data available for each treatment modality are summarized in this review. The clinical relationships between CRS and its comorbidities are also discussed. RECENT FINDINGS: The most promising advances in rhinosinusitis management involve the use of mAbs (anti-IgE, anti-IL-5, anti-IL-4Ralpha) in trials of CRS with nasal polyposis. Otherwise, the mainstays of treatment for both ARS and CRS have largely remained the same over the past several years. SUMMARY: The treatment of ARS primarily involves symptomatic control with intranasal corticosteroids and nasal saline irrigation; antibiotics should be reserved for the patients who are believed to have bacterial rhinosinusitis. Treating CRS effectively involves using intranasal corticosteroids and irrigation, systemic corticosteroids, and potentially systemic antibiotics. Biologics (mAbs) have shown benefit in clinical studies. Providers should also be aware of concomitant disease processes that may afflict patients with CRS. PMID- 27253486 TI - Emerging evidence of the role of gut microbiota in the development of allergic diseases. AB - PURPOSE OF REVIEW: The purpose is to review recent studies examining the role of gut microbiota in allergic diseases and asthma. RECENT FINDINGS: Work in experimental models gives further evidence that a disturbed gut microbiota influences the propensity to develop allergic manifestations, and that changing the gut microbiota by dietary means (high fiber/acetate or prebiotics) in pregnancy may reduce the risk of allergic airways disease and food allergy in the offspring, respectively. The gut microbiome in established allergic disease and prior to disease onset has also been assessed in clinical trials. One study demonstrated a strong association between high abundance of Faecalibacterium prausnitzii and decreased levels of butyrate and propionate, and established eczema. Lower relative abundance of Ruminococcaceae appears to be implicated in food sensitization and to precede the development of atopic eczema. Decreased relative abundance of Lachnospira, Veillonella, Faecalibacterium, and Rothia in early infancy was reported to be associated with increased asthma risk. Inoculation of germ-free mice with these genera decreased airway inflammation in their offspring thereby proposing a causal role of bacteria in preventing allergic airways disease. SUMMARY: Gut microbiome research is an actively developing field. Although candidate bacterial taxa have been reported it still remains unclear which bacteria (or other microbes), in which numbers and combinations, and when during the gut colonization process may prevent allergic diseases and asthma. There is still a call for standardized approaches that will enable direct comparison of different studies. PMID- 27253489 TI - Highly Stable Lyophilized Homogeneous Bead-Based Immunoassays for On-Site Detection of Bio Warfare Agents from Complex Matrices. AB - This study shows the development of dry, highly stable immunoassays for the detection of bio warfare agents in complex matrices. Thermal stability was achieved by the lyophilization of the complete, homogeneous, bead-based immunoassay in a special stabilizing buffer, resulting in a ready-to-use, simple assay, which exhibited long shelf and high-temperature endurance (up to 1 week at 100 degrees C). The developed methodology was successfully implemented for the preservation of time-resolved fluorescence, Alexa-fluorophores, and horse radish peroxidase-based bead assays, enabling multiplexed detection. The multiplexed assay was successfully implemented for the detection of Bacillus anthracis, botulinum B, and tularemia in complex matrices. PMID- 27253491 TI - Exploring U.S. Social Work Students' Sexual Attitudes and Abortion Viewpoints. AB - Social workers frequently engage with sexual and reproductive health topics, yet a notable paucity of social work research exists regarding abortion. Informed by overlapping theoretical frameworks of human rights and reproductive justice, this study examined a large, nationwide survey of social work students in the United States (N = 504). Linear regressions indicated that students' endorsements of permissive sexual attitudes and support for birth control are inversely associated with holding anti-choice abortion views. Moreover, distinct relationships were found among sociodemographic characteristics and abortion attitudes and knowledge, suggesting that social work education efforts regarding contentious reproductive and sexual health topics should also focus on nuances of cultural competence and diversity, as well as general human rights principles and professional ethics. PMID- 27253492 TI - Rh-catalysed [5 + 1] cycloaddition of allenylcyclopropanes and CO: reaction development and application to the formal synthesis of (-)-galanthamine. AB - A Rh-catalysed [5 + 1] cycloaddition of allenylcyclopropanes and CO has been developed to synthesize functionalized 2-methylidene-3,4-cyclohexenones. The scope of this methodology has been investigated, showing that various functional groups can be tolerated. Both di- and tri-substituted allenylcyclopropanes can be applied to this cycloaddition and the [5 + 1] cycloadducts with the E configuration were obtained as the major products. In addition, the present [5 + 1] cycloaddition reaction has been utilized as a key step in the formal synthesis of the natural product (-)-galanthamine. PMID- 27253487 TI - New advances in invasive aspergillosis immunobiology leading the way towards personalized therapeutic approaches. AB - Invasive aspergillosis (IA) remains a devastating disease in immune compromised patients despite significant advances in our understanding of fungal virulence and host defense mechanisms. In this review, we summarize important research advances in the fight against IA with particular focus on early events in the interactions between Aspergillus fumigatus and the host that occur in the respiratory tract. Advances in understanding mechanisms of immune effector cell recruitment, antifungal effector mechanisms, and how the dynamic host-fungal interaction alters the local microenvironment to effect outcomes are highlighted. These advances illustrate exciting new therapeutic opportunities, but also emphasize the importance of understanding each unique fungus-host interaction for improving patient outcomes. PMID- 27253493 TI - Conjugation to Poly(amidoamine) Dendrimers and Pulmonary Delivery Reduce Cardiac Accumulation and Enhance Antitumor Activity of Doxorubicin in Lung Metastasis. AB - Lung is one of the most common sites to which almost all other primary tumors metastasize. The major challenges in the chemotherapy of lung metastases include the low drug concentration found in the tumors and high systemic toxicity upon systemic administration. In this study, we combine local lung delivery and the use of nanocarrier-based systems for improving pharmacokinetics and biodistribution of the therapeutics to fight lung metastases. We investigate the impact of the conjugation of doxorubicin (DOX) to carboxyl-terminated poly(amidoamine) dendrimers (PAMAM) through a bond that allows for intracellular triggered release, and the effect of pulmonary delivery of the dendrimer-DOX conjugate in decreasing tumor burden in a lung metastasis model. The results show a dramatic increase in efficacy of DOX treatment of the melanoma (B16-F10) lung metastasis mouse model upon pulmonary administration of the drug, as indicated by decreased tumor burden (lung weight) and increased survival rates of the animals (male C57BL/6) when compared to iv delivery. Conjugation of DOX further increased the therapeutic efficacy upon lung delivery as indicated by the smaller number of nodules observed in the lungs when compared to free DOX. These results are in agreement with the biodistribution characteristics of the DOX upon pulmonary delivery, which showed a longer lung accumulation/retention compared to iv administration. The distribution of DOX to the heart tissue is also significantly decreased upon pulmonary administration, and further decreased upon conjugation. The results show, therefore, that pulmonary administration of DOX combined to conjugation to PAMAM dendrimer through an intracellular labile bond is a potential strategy to enhance the therapeutic efficacy and decrease systemic toxicity of DOX. PMID- 27253494 TI - "Balancing" the Block Davidson-Liu Algorithm. AB - We describe a simple modification ("balancing") of the block Davidson-Liu eigenvalue algorithm which allows the norms of the Krylov search directions to decrease naturally as convergence is approached. In the context of integral direct configuration interaction singles and time-dependent density functional theory, this provides for efficient utilization of density-based screening. Tests within the TeraChem GPGPU code exhibit speedups of ~2* on systems with up to 1500 atoms, with negligible loss in accuracy. PMID- 27253488 TI - Butyrate regulates the expression of inflammatory and chemotactic cytokines in human acute leukemic cells during apoptosis. AB - Butyrate is a histone deacetylase inhibitor implicated in many studies as a potential therapy for various forms of cancer. High concentrations of butyrate (>1.5mM) have been shown to activate apoptosis in several cancer cell lines including prostate, breast, and leukemia. Butyrate is also known to influence multiple signaling pathways that are mediators of cytokine production. The purpose of this study was to evaluate the impact of high concentrations of butyrate on the cancer microenvironment vis-a-vis apoptosis, cellular migration, and capacity to modulate cytokine expression in cancer cells. The results indicate that high concentrations of butyrate induced a 2-fold activation of caspase-3 and reduced cell viability by 60% in U937 leukemia cells. Within 24h, butyrate significantly decreased the levels of chemokines CCL2 and CCL5 in HL-60 and U937 cells, and decreased CCL5 in THP-1 leukemia cells. Differential effects were observed in treatments with valproic acid for CCL2 and CCL5 indicating butyrate-specificity. Many of the biological effects examined in this study are linked to activation of the AKT and MAPK signaling pathways; therefore, we investigated whether butyrate alters the levels of phosphorylated forms of these signaling proteins and how it correlated with the expression of chemokines. The results show that butyrate may partially regulate CCL5 production via p38 MAPK. The decrease in p-ERK1/2 and p-AKT levels correlated with the decrease in CCL2 production. These data suggest that while promoting apoptosis, butyrate has the potential to influence the cancer microenvironment by inducing differential expression of cytokines. PMID- 27253495 TI - Rhizobium strains differ considerably in outer membrane permeability and polymyxin B resistance. AB - Six rhizobium (Rhizobium leguminosarum bv. Trifolii TA1, Sinorhizobium meliloti 1021, Mesorhizobium huakuii IFO 15243(T), Ochrobactrum lupini LUP 21(T), Bradyrhizobium japonicum USDA110 and B. elkanii USDA 76) and two Escherichia coli strains (E. coli ATCC 25922 and E. coli HB 101) were compared in respect to polymyxin B and EDTA resistance, as well as bacterial outer membrane (OM) permeability to a fluorescent hydrophobic agent (N-phenyl-1-naphthylamine - NPN). TEM (Transmission Electron Microscopy) and a microbial test demonstrated that all the rhizobia were much more resistant to polymyxin B in comparison with E. coli strains. EDTA and polymyxin B enhance permeability of B. japonicum and O. lupini OM. Other rhizobia incorporated NPN independently of the presence of membrane deteriorating agents; however, the level of fluorescence (measured as NPN absorption) was strain dependent. PMID- 27253496 TI - Effective and complex stimulation of the biodegradation system of fungus Cerrena unicolor by rapeseed meal fermentation. AB - The effect of supplementation of medium with rapeseed meal (RM) on production of biotechnologically important enzymes was investigated in submerged cultures of the white rot fungus Cerrena unicolor. The addition of RM (3.5% w/v) distinctly stimulated the activities of laccase, chitinase, and beta-glucosidase. As compared to the control, the activities of chitinase, beta-glucosidase, and laccase in the RM supplemented cultures were up to 4.1, 8.4, and 3.9 times higher, respectively. The results of the spectrophotometric and spectrofluorometric measurements were additionally confirmed by zymographic analysis of the samples. The level of sugars and phenolic compounds as well as the antioxidative ability of fungal preparations were also determined. The results obtained indicate that the submerged liquid fermentation of rapeseed meal can be proposed as an inexpensive and very effective method for biotechnological production of chitinase, beta-glucosidase, and laccase by C. unicolor. PMID- 27253497 TI - School psychology recruitment research characteristics and implications for increasing racial and ethnic diversity. AB - Shortages of school psychologists and the underrepresentation of minorities in school psychology represent longstanding concerns. Scholars recommend that one way to address both issues is to recruit individuals from racially and ethnically diverse backgrounds into school psychology. The purpose of this study was to explore the characteristics and minority focused findings of school psychology recruitment studies conducted from 1994 to 2014. Using an electronic search that included specified databases, subject terms and study inclusion criteria along with a manual search of 10 school psychology focused journals, the review yielded 10 published, peer-reviewed recruitment studies focused primarily on school psychology over the 20-year span. Two researchers coded these 10 studies using a rigorous coding process that included a high level of inter rater reliability. Results suggest that the studies utilized varied methodologies, primarily sampled undergraduate populations, and mostly included White participants. Five studies focused on minority populations specifically. These studies indicate that programs should actively recruit minority undergraduates and offer financial support to attract minority candidates. Implications suggest a need for more recruitment research focused on minority populations and the implementation and evaluation of minority recruitment models. (PsycINFO Database Record PMID- 27253498 TI - Pharmacodynamic and pharmacokinetic assessment of fluticasone furoate + vilanterol for the treatment of asthma. AB - INTRODUCTION: The pharmacokinetic (PK) and pharmacodynamic (PD) effects of long acting beta2-agonists and mostly inhaled corticosteroids (ICSs) shape the efficacy and safety of these agents in the treatment of asthma. In fact, the PK and PD characteristics of the drug largely determine the degree of pulmonary targeting Areas covered. In this review, we summarize the PK and PD properties of inhaled fluticasone furoate (FF) and vilanterol trifenatate (VI) and their fixed dose combination (FDC) for the treatment of asthma Expert opinion. It is difficult to interpret the data that we have described because the preclinical and clinical development of FF/VI FDC was not really based on solid information on quantitative PK/PD approach. Unfortunately, for both FF and VI we only know concentrations in systemic blood, a compartment that is downstream of both target and non-target respiratory tissue. This lack of information does not allow us to understand the temporal relationship between the delivered dose and the drug concentration at the sites of action within the lungs. In addition, all studies performed with FF and VI did not address the fundamental issue that asthma can significantly alter lung deposition, absorption and also clearance of inhaled medicines. PMID- 27253508 TI - Colour imaging in the monitoring and documentation of choroidal naevi. Are Optomap colour images adequate for this purpose? AB - An audit project to evaluate and compare three different imaging systems used to photograph choroidal naevi and to determine whether the Optos Optomap((r)) can be used as the only colour image capture system for monitoring and documenting choroidal naevi. A further aim was to assess whether existing protocols could be improved to accurately document position and appearance of choroidal naevi. Twenty patients with choroidal naevi were photographed on three different colour image capture systems. Colour images were taken on the Optomap((r)) wide field P200MA camera; the Zeiss FF450plus((r)) mydriatic camera and the Topcon TRC NW6S((r)). All images were reviewed retrospectively by a medical retina consultant (SD) who completed a questionnaire to determine the most effective photographic system(s) in demonstrating the location of the naevi and the features of the condition. The Optomap((r)) was the most effective in pinpointing the location of the naevus and the Zeiss FF450plus mydriatic camera best captured the features of the naevus. The non-mydriatic camera was rated the least satisfactory for both tasks. The location of the naevus on the retina should determine the choice of modality. If it is possible to photograph the lesion and include the optic disc or central macula, then the mydriatic camera is considered the best modality for recording both the position and features of the pathology. However, if it is not possible, because of the location, to include both the disc or central macula with the lesion in the same frame, then the Optomap((r)) should be used to photograph the naevus to record its position and ideally a colour image on the mydriatic camera should also be taken to record the appearance of the lesion. PMID- 27253509 TI - Targeting hypoxia to overcome radiation resistance in head & neck cancers: real challenge or clinical fairytale? AB - INTRODUCTION: Tumor hypoxia is a major cause for failure of therapy in patients with inoperable head and neck cancers. AREAS COVERED: Various anti-hypoxic treatment strategies (e.g. hyperbaric oxygenation, hypoxic cell sensitizers) have been tested in clinical trials in head and neck cancer over the past 30 years and have shown modest improvements in combination with radiotherapy in meta-analyses. Anemia worsens tumor hypoxia, but anemia correction had no significant effect. New approaches (e.g. anti-HIF-directed molecular therapies) have just entered early clinical studies and data are lacking. Expert commentary: A new attractive and promising approach derives from recent advances in imaging and radiotherapy delivery. Progress in imaging of hypoxia (e.g. by positron emission tomography) can select patients for specific therapies and may, in particular, facilitate anti-hypoxia-directed radiotherapy which has become feasible with advanced radiotherapy techniques (IMRT with 'dose-painting'). The combination of both methods may offer a powerful tool for effective targeting of hypoxia in the near future. PMID- 27253510 TI - Global Biodiversity Loss by Freshwater Consumption and Eutrophication from Swiss Food Consumption. AB - We investigated water-related resource use, emissions and ecosystem impacts of food consumed in Switzerland. To do so, we coupled LCA methodologies on freshwater consumption, freshwater eutrophication and the consequent local and global biodiversity impacts with Swiss customs data and multiregional input output analysis. Most of the resource use, emissions and impacts occur outside the national boundaries which illustrates the extent of environmental outsourcing facilitated by international trade. Countries that are severely affected by Swiss food consumption include Spain, the United States and Ecuador. Cocoa, coffee, and almonds stood out as products with high impacts. By identifying spatial hotspots and impactful products, awareness of policy-makers as well as individual consumers can be raised and efforts of detailed assessments can be streamlined. However, political and economic constraints and the resistance by individual consumers limit the high potential of changes in diets and trade relations to decrease the environmental impacts of food. PMID- 27253511 TI - Cognitive Tests and Determining Fitness to Drive in Dementia: A Systematic Review. AB - Evidence has shown that although all individuals with dementia will eventually need to stop driving, most can continue to drive safely early in the disease. Fitness to drive needs to be monitored, and the use of cognitive testing to determine driver safety has been suggested. This review is the first to examine cognitive test results pertaining only to individuals with dementia. The aim was to examine the relationship between cognitive tests and driving to determine whether a cognitive assessment can be implemented as a tool to examine driver safety. A systematic review of 28 studies investigating the relationship between cognitive functioning and driving in individuals with dementia was conducted. The results of this review demonstrated a lack of consistency in the findings, with some studies showing a relationship between cognitive testing and driving performance for individuals with dementia, whereas others did not. Results relating to individual cognitive tests and measures confined to a single cognitive domain were variable and not consistently associated with driving performance. Studies consistently found that composite batteries predicted driving performance. The findings from this review support the use of composite batteries comprising multiple individual tests from different cognitive domains in predicting driving performance for individuals with dementia. Scores on individual tests or tests of a single cognitive domain did not predict driver safety. The composite batteries that researchers have examined are not clinically usable because they lack the ability to discriminate sufficiently between safe and unsafe drivers. Researchers need to develop a reliable, valid composite battery that can correctly determine driver safety in individuals with dementia. PMID- 27253513 TI - Treatment of Regional Lymph Nodes in Breast Cancer-Evidence in Favor of Radiation Therapy. PMID- 27253512 TI - 6-Substituted 2-Aminopurine-2'-deoxyribonucleoside 5'-Triphosphates that Trace Cytosine Methylation. AB - Gene expression is extensively regulated by the occurrence and distribution of the epigenetic marker 2'-deoxy 5-methylcytosine (5mC) in genomic DNA. Because of its effects on tumorigenesis there is an important link to human health. In addition, detection of 5mC can serve as an outstanding biomarker for diagnostics as well as for disease therapy. Our previous studies have already shown that, by processing O(6) -alkylated 2'-deoxyguanosine triphosphate (dGTP) analogues, DNA polymerases are able to sense the presence of a single 5mC unit in a template. Here we present the synthesis and evaluation of an extended toolbox of 6 substituted 2-aminopurine-2'-deoxyribonucleoside 5'-triphosphates modified at position 6 with various functionalities. We found that sensing of 5-methylation by this class of nucleotides is more general, not being restricted to O(6) -alkyl modification of dGTP but also applying to other functionalities. PMID- 27253515 TI - Failure Modes during Low-Voltage Electrowetting. AB - Low-voltage electrowetting devices allow significant contact angle changes below a 50 V bias; however, operation under prolonged cycling and failure modes have not yet been sufficiently elucidated. In this work, the failure modes and performance degradation of Cytop (23-210 nm)/aluminum oxide (15-44 nm) bilayers have been investigated. Contact angle and leakage current were measured during stepped voltage measurements up to failure, showing three electrowetting response regimes: ideal Young-Lippmann behavior, contact angle saturation, and dielectric breakdown. The onset of ionic conduction in aluminum oxide and the resulting breakdown control when the layer would ultimately fail, but the thickness of the Cytop layer determined the achievable contact angle versus voltage characteristics. Cyclic electrowetting measurements studied the repeatability of contact angle change using an applied voltage above or below the voltage drop needed for polymer breakdown (VT). Results show repeatable electrowetting below VT and a rapidly diminishing contact angle response above VT. The leakage current and injected charge cannot be used to comprehensively assess the stability of the system during operation. The contact potential difference measured with a Kelvin probe provides an alternative means of assessing the extent of the damage. PMID- 27253514 TI - Fecal Immunochemical Tests Combined With Other Stool Tests for Colorectal Cancer and Advanced Adenoma Detection: A Systematic Review. AB - OBJECTIVES: Despite moderate to high detection rates of fecal immunochemical tests (FITs) of colorectal cancer (CRC), detection of adenomas remains limited. Further stool tests exist, which are not used in routine practice, such as DNA or RNA markers and protein markers. We aimed at systematically investigating and summarizing evidence for diagnostic performance of combinations of FIT with other stool tests compared with FIT alone in early detection of CRC and its precursors. METHODS: We systematically reviewed studies that evaluated FITs in combination with other stool tests and compared measures of diagnostic accuracy with and without additional stool tests. PubMed and Web of Science were searched from inception to May 2015. Reference lists of eligible studies were also screened. Two reviewers extracted data independently. RESULTS: Some of the reports on DNA, RNA, or tissue tests, including tests based on DNA mutations, methylation, and integrity in selected genes as well as microRNA expression, showed some improvements of diagnostic test accuracy. In contrast, so far assessed stool protein markers did generally not lead to substantial improvements in performance of FIT when added to the latter. Many marker combinations were reported only in one study each, and few studies were conducted in a true screening setting. CONCLUSIONS: Several stool markers show potential to improve performance of FITs. However, the results require confirmation in further studies, which should also evaluate the costs and cost-effectiveness of combined screening strategies. PMID- 27253516 TI - Intermolecular Hybridization Creating Nanopore Orbital in a Supramolecular Hydrocarbon Sheet. AB - Molecular orbital engineering is a key ingredient for the design of organic devices. Intermolecular hybridization promises efficient charge carrier transport but usually requires dense packing for significant wave function overlap. Here we use scanning tunneling spectroscopy to spatially resolve the electronic structure of a surface-confined nanoporous supramolecular sheet of a prototypical hydrocarbon compound featuring terminal alkyne (-CCH) groups. Surprisingly, localized nanopore orbitals are observed, with their electron density centered in the cavities surrounded by the functional moieties. Density functional theory calculations reveal that these new electronic states originate from the intermolecular hybridization of six in-plane pi-orbitals of the carbon-carbon triple bonds, exhibiting significant electronic splitting and an energy downshift of approximately 1 eV. Importantly, these nanopore states are distinct from previously reported interfacial states. We unravel the underlying connection between the formation of nanopore orbital and geometric arrangements of functional groups, thus demonstrating the generality of applying related orbital engineering concepts in various types of porous organic structures. PMID- 27253517 TI - Patient experiences of training and transition to home haemodialysis: A mixed methods study. AB - AIM: This study aims to describe patients' perspectives on the transition to home haemodialysis. METHODS: Up to three sequential semi-structured interviews were conducted with 20 patients during the transition to home haemodialysis at an Australian renal unit. Transcripts were analysed thematically. Participants completed a satisfaction questionnaire after commencing home haemodialysis. RESULTS: We identified six themes: persevering despite trepidations (diminishing intimidation of machinery, acquiescing to fatal risks, reconciling fears of cannulation, dispelling concerns of neglect and tolerating necessary concessions); optimizing the learning pathway (practising problem solving, learning from mistakes, grasping technical complexity, minimizing cognitive overload and progressing at own pace); developing confidence (believing in own abilities, adapting to independence, depending on caregiver partnership and faith in crisis support); interrupted transition momentum (lacking individual attention, language barriers, installation delays, interfering illness and complications and acclimatizing to new conditions); noticing immediate gains (reclaiming lifestyle normality, satisfying self-sufficiency, personalizing treatment regime and thriving in a positive environment); and depleting resources and energy (exhaustion with gruelling routine, confronting medicalization of the home, draining financial reserves and imposing family burden). Fewer than 30% of respondents indicated low satisfaction with staff availability domains, staff interpersonal domains or technical domains. CONCLUSION: Home haemodialysis training fosters confidence in patients; however, many patients experience stress because of medical isolation, treatment responsibilities, family impositions and financial difficulties. Addressing patient's on-going psychosocial concerns may alleviate burdens on patients and their families during the transition to home haemodialysis. PMID- 27253518 TI - CD44 Splice Variant v8-10 as a Marker of Serous Ovarian Cancer Prognosis. AB - CD44 is a transmembrane hyaluronic acid receptor gene that encodes over 100 different tissue-specific protein isoforms. The most ubiquitous, CD44 standard, has been used as a cancer stem cell marker in ovarian and other cancers. Expression of the epithelial CD44 variant containing exons v8-10 (CD44v8-10) has been associated with more chemoresistant and metastatic tumors in gastrointestinal and breast cancers, but its role in ovarian cancer is unknown; we therefore investigated its use as a prognostic marker in this disease. The gene expression profiles of 254 tumor samples from The Cancer Genome Atlas RNAseqV2 were analyzed for the presence of CD44 isoforms. A trend for longer survival was observed in patients with high expression of CD44 isoforms that include exons v8-10. Immunohistochemical (IHC) analysis of tumors for presence of CD44v8-10 was performed on an independent cohort of 210 patients with high-grade serous ovarian cancer using a tumor tissue microarray. Patient stratification based on software analysis of staining revealed a statistically significant increase in survival in patients with the highest levels of transmembrane protein expression (top 10 or 20%) compared to those with the lowest expression (bottom 10 and 20%) (p = 0.0181, p = 0.0262 respectively). Expression of CD44v8-10 in primary ovarian cancer cell lines was correlated with a predominantly epithelial phenotype characterized by high expression of epithelial markers and low expression of mesenchymal markers by qPCR, Western blot, and IHC. Conversely, detection of proteolytically cleaved and soluble extracellular domain of CD44v8 10 in patient ascites samples was correlated with significantly worse prognosis (p<0.05). Therefore, presence of transmembrane CD44v8-10 on the surface of primary tumor cells may be a marker of a highly epithelial tumor with better prognosis while enzymatic cleavage of CD44v8-10, as detected by presence of the soluble extracellular domain in ascites fluid, may be indicative of a more metastatic disease and worse prognosis. PMID- 27253519 TI - Progress in understanding the safety and efficacy of Janus kinase inhibitors for treatment of rheumatoid arthritis. AB - INTRODUCTION: Treatment of rheumatoid arthritis (RA) has improved considerably following the advent of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, these drugs require special storage and transportation. Janus kinase (JAK) inhibitors are oral synthetic DMARDs that inhibit the non-receptor tyrosine kinase family Janus kinase. Recently, many JAK inhibitors are being developed as new therapies for patients with RA. AREAS COVERED: In this article, we mainly review the efficacy and safety of JAK inhibitors currently under investigation. Tofacitinib has already been approved in 43 countries except in the EU. Results of three JAK inhibitors (baricitinib, decernotinib, and peficitinib) in phase III are consistent with that of tofacitinib. Tofacitinib and baricitinib were partially effective in patients who had an inadequate response to biological DMARDs. Expert commentary: JAK kinase inhibitors provide a new therapeutic approach for rheumatoid arthritis. Meanwhile, further studies are needed to determine their risk-benefit ratio and the most appropriate patients suitable for such therapy. PMID- 27253520 TI - Ordered PdCu-Based Nanoparticles as Bifunctional Oxygen-Reduction and Ethanol Oxidation Electrocatalysts. AB - The development of superior non-platinum electrocatalysts for enhancing the electrocatalytic activity and stability for the oxygen-reduction reaction (ORR) and liquid fuel oxidation reaction is very important for the commercialization of fuel cells, but still a great challenge. Herein, we demonstrate a new colloidal chemistry technique for making structurally ordered PdCu-based nanoparticles (NPs) with composition control from PdCu to PdCuNi and PtCuCo. Under the dual tuning on the composition and intermetallic phase, the ordered PdCuCo NPs exhibit better activity and much enhanced stability for ORR and ethanol-oxidation reaction (EOR) than those of disordered PdCuM NPs, the commercial Pt/C and Pd/C catalysts. The density functional theory (DFT) calculations reveal that the improved ORR activity on the PdCuM NPs stems from the catalytically active hollow sites arising from the ligand effect and the compressive strain on the Pd surface owing to the smaller atomic size of Cu, Co, and Ni. PMID- 27253521 TI - Splenectomy is not indicated in living donor liver transplantation. AB - Simultaneous splenectomy (SPX) is preferentially performed in living donor liver transplantation (LDLT) to modulate portal flow; increase postoperative platelet count, especially among those with hepatitis C virus (HCV) infection; and modulate the immunologic status in ABO-incompatible cases. The negative effects of the procedure, however, are not well established. Records of 395 LDLTs performed at our institution, including 169 (42.8%) patients with simultaneous SPX and 226 (57.2%) patients with spleen preservation, were reviewed with special reference to the simultaneous SPX cases. The most common indication for SPX was HCV-related disease (n = 114), followed by low preoperative platelet count (n = 52), and other reasons (n = 3). Simultaneous splenectomy did not increase the platelet count in the early postoperative period, but the incidence of reoperation for postoperative hemorrhage was increased, mainly at the SPX site, within the first week. In addition, the operative time, intraoperative blood loss, and incidence of lethal infectious disease were significantly higher in the SPX group, whereas the incidence of small-for-size syndrome was comparable between groups. Finally, SPX was an independent predictor for both postoperative hemorrhage (odds ratio [OR] = 2.451; 95% confidence interval [CI] = 1.285-4.815; P = 0.006) and lethal infectious complication (OR = 3.748; 95% CI = 1.148-14.001; P = 0.03). In conclusion, on the basis of the present findings, we do not recommend simultaneous SPX in LDLT. Liver Transplantation 22 1526-1535 2016 AASLD. PMID- 27253522 TI - Predictive value of the composition of the vaginal microbiota in bacterial vaginosis, a dynamic study to identify recurrence-related flora. AB - Bacterial vaginosis (BV) is a highly prevalent disease in women, and increases the risk of pelvic inflammatory disease. It has been given wide attention because of the high recurrence rate. Traditional diagnostic methods based on microscope providing limited information on the vaginal microbiota increase the difficulty in tracing the development of the disease in bacteria resistance condition. In this study, we used deep-sequencing technology to observe dynamic variation of the vaginal microbiota at three major time points during treatment, at D0 (before treatment), D7 (stop using the antibiotics) and D30 (the 30-day follow-up visit). Sixty-five patients with BV were enrolled (48 were cured and 17 were not cured), and their bacterial composition of the vaginal microbiota was compared. Interestingly, we identified 9 patients might be recurrence. We also introduced a new measurement point of D7, although its microbiota were significantly inhabited by antibiotic and hard to be observed by traditional method. The vaginal microbiota in deep-sequencing-view present a strong correlation to the final outcome. Thus, coupled with detailed individual bioinformatics analysis and deep sequencing technology, we may illustrate a more accurate map of vaginal microbial to BV patients, which provide a new opportunity to reduce the rate of recurrence of BV. PMID- 27253523 TI - Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations. AB - The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1 diabetes. PMID- 27253524 TI - Correction: A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies. AB - [This corrects the article DOI: 10.1371/journal.pntd.0004349.]. PMID- 27253525 TI - Treatment of Oral Candidiasis Using Photodithazine(r)- Mediated Photodynamic Therapy In Vivo. AB - This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT) in the treatment of oral candidiasis in a murine model using Photodithazine(r) (PDZ). This model of oral candidiasis was developed to allow the monitoring of the infection and the establishment of the aPDT treatment. Six week-old female mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDZ-mediated aPDT and nystatin treatment were carried out for 5 consecutive days with one application per day. The macroscopic evaluation of oral lesions was performed. After each treatment, the tongue was swabbed to recover C. albicans cells. Viable colonies were quantified and the number of CFU/ml determined. The animals were sacrificed 24 hours and 7 days after treatment and the tongues were surgically removed for histological analysis and analysis of inflammatory cytokines expression (IL-1, TNF-alpha and IL-6) by RT-qPCR. Data were analyzed by two-way ANOVA. PDZ-mediated aPDT was as effective as Nystatin (NYS group) in the inactivation of C. albicans, reducing 3 and 3.2 logs10 respectively, 24 h after treatment (p<0.05). Animals underwent PDZ mediated aPDT showed complete remission of oral lesions, while animals treated with NYS presented partial remission of oral lesions in both periods assessed. Histological evaluation revealed mild inflammatory infiltrate in the groups treated with aPDT and NYS in both periods assessed. The aPDT induced the TNF alpha expression when compared with the control (P-L-) (p<0.05), 24 h and 7 days after treatment. In summary, the murine model developed here was able to mimic the infection and PDZ-mediated aPDT was effective to treat mice with oral candidiasis. PMID- 27253526 TI - Effect of a Brown Rice Based Vegan Diet and Conventional Diabetic Diet on Glycemic Control of Patients with Type 2 Diabetes: A 12-Week Randomized Clinical Trial. AB - OBJECTIVE: Several intervention studies have suggested that vegetarian or vegan diets have clinical benefits, particularly in terms of glycemic control, in patients with type 2 diabetes (T2D); however, no randomized controlled trial has been conducted in Asians who more commonly depend on plant-based foods, as compared to Western populations. Here, we aimed to compare the effect of a vegan diet and conventional diabetic diet on glycemic control among Korean individuals. MATERIALS AND METHODS: Participants diagnosed with T2D were randomly assigned to follow either a vegan diet (excluding animal-based food including fish; n = 46) or a conventional diet recommended by the Korean Diabetes Association 2011 (n = 47) for 12 weeks. HbA1c levels were measured at weeks 0, 4, and 12, and the primary study endpoint was the change in HbA1c levels over 12 weeks. RESULTS: The mean HbA1c levels at weeks 0, 4, and 12 were 7.7%, 7.2%, and 7.1% in the vegan group, and 7.4%, 7.2%, and 7.2% in the conventional group, respectively. Although both groups showed significant reductions in HbA1C levels, the reductions were larger in the vegan group than in the conventional group (-0.5% vs. -0.2%; p-for interaction = 0.017). When only considering participants with high compliance, the difference in HbA1c level reduction between the groups was found to be larger (-0.9% vs. -0.3%). The beneficial effect of vegan diets was noted even after adjusting for changes in total energy intake or waist circumference over the 12 weeks. CONCLUSION: Both diets led to reductions in HbA1c levels; however, glycemic control was better with the vegan diet than with the conventional diet. Thus, the dietary guidelines for patients with T2D should include a vegan diet for the better management and treatment. However, further studies are needed to evaluate the long-term effects of a vegan diet, and to identify potential explanations of the underlying mechanisms. TRIAL REGISTRATION: CRiS KCT0001771. PMID- 27253527 TI - Public Service by a Selfish Gene: A Domesticated Transposase Antagonizes Polycomb Function. PMID- 27253528 TI - Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells. AB - Bacterial lipopolysaccharide (LPS) induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3), methylation (H3K4, H3K9, H3K27) and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene. PMID- 27253583 TI - Comparative Analyses between Skeletal Muscle miRNAomes from Large White and Min Pigs Revealed MicroRNAs Associated with Postnatal Muscle Hypertrophy. AB - The molecular mechanism regulated by microRNAs (miRNAs) that underlies postnatal hypertrophy of skeletal muscle is complex and remains unclear. Here, the miRNAomes of longissimus dorsi muscle collected at five postnatal stages (60, 120, 150, 180, and 210 days after birth) from Large White (commercial breed) and Min pigs (indigenous breed of China) were analyzed by Illumina sequencing. We identified 734 miRNAs comprising 308 annotated miRNAs and 426 novel miRNAs, of which 307 could be considered pig-specific. Comparative analysis between two breeds suggested that 60 and 120 days after birth were important stages for skeletal muscle hypertrophy and intramuscular fat accumulation. A total of 263 miRNAs were significantly differentially expressed between two breeds at one or more developmental stages. In addition, the differentially expressed miRNAs between every two adjacent developmental stages in each breed were determined. Notably, ssc-miR-204 was significantly more highly expressed in Min pig skeletal muscle at all postnatal stages compared with its expression in Large White pig skeletal muscle. Based on gene ontology and KEGG pathway analyses of its predicted target genes, we concluded that ssc-miR-204 may exert an impact on postnatal hypertrophy of skeletal muscle by regulating myoblast proliferation. The results of this study will help in elucidating the mechanism underlying postnatal hypertrophy of skeletal muscle modulated by miRNAs, which could provide valuable information for improvement of pork quality and human myopathy. PMID- 27253584 TI - Why the resistance to statistical innovations? A comment on Sharpe (2013). AB - Sharpe's (2013) article considered reasons for the apparent resistance of substantive researchers to the adoption of newer statistical methods recommended by quantitative methodologists, and possible ways to reduce that resistance, focusing on improved communication. The important point that Sharpe missed, however, is that because research methods vary radically from one subarea of psychology to another, a particular statistical innovation may be much better suited to some subareas than others. Although there may be some psychological or logistical explanations that account for resistance to innovation in general, to fully understand the resistance to any particular innovation, it is necessary to consider how that innovation impacts specific subareas of psychology. In this comment, I focus on the movement to replace null hypothesis significance testing (NHST) with reports of effect sizes and/or confidence intervals, and consider its possible impact on research in which only the direction of the effect is meaningful, and there is no basis for predicting specific effect sizes (and very large samples are rarely used). There are numerous examples of these studies in social psychology, for instance, such as those that deal with priming effects. I use a study in support of terror management theory as my main example. I conclude that the degree to which statistical reformers have overgeneralized their criticisms of NHST, and have failed to tailor their recommendations to different types of research, may explain some of the resistance to abandoning NHST. Finally, I offer suggestions for improved communication to supplement those presented by Sharpe. (PsycINFO Database Record PMID- 27253585 TI - Initial management and outcomes after superficial thrombophlebitis: The Cardiovascular Research Network Venous Thromboembolism study. AB - Although superficial thrombophlebitis (SVTE) is generally considered a benign, self-limited disease, accumulating evidence suggests that it often leads to more serious forms of venous thromboembolism. We reviewed the medical charts of 329 subjects with SVTE from the Cardiovascular Research Network Venous Thromboembolism cohort study to collect information on the acute treatment of SVTE and subsequent diagnosis of deep venous thrombosis within 1 year. All participants received care within Kaiser Permanente Northern California, a large, integrated healthcare delivery system. Fourteen (4.3%) subjects with SVTE received anticoagulants, 148 (45.0%) were recommended antiplatelet agents or nonsteroidal anti-inflammatory drugs, and in 167 (50.8%) there was no documented antithrombotic therapy. In the year after SVTE diagnosis, 19 (5.8%) patients had a subsequent diagnosis of a deep venous thrombosis or pulmonary embolism. In conclusion, clinically significant venous thrombosis within a year after SVTE was uncommon in our study despite infrequent use of antithrombotic therapy. Journal of Hospital Medicine 2016;11:432-434. (c) 2016 Society of Hospital Medicine. PMID- 27253586 TI - Avoiding contrast-enhanced computed tomography scans in patients with shellfish allergies. PMID- 27253587 TI - Real-Time Imaging of Single HIV-1 Disassembly with Multicolor Viral Particles. AB - Viral disassembly is poorly understood and related to the infection mechanism. However, directly observing the process in living cells remains technically challenging. In this study, the genome RNA, capsid, and matrix protein of the HIV 1 virus were labeled with a Ru(II) complex ([Ru(phen)2(dppz)](2+)), the TC FlAsH/ReAsH system, and EGFP/ECFP, respectively. Using the multicolored virus and single-particle imaging, we were able to track the sequential disassembly process of single HIV-1 virus particles in live host cells. Approximately 0.1% of viral particles were observed to undergo a sequential disassembly process at 60-120 min post infection. The timing and efficiency of the disassembly were influenced by the cellular factor CypA and reverse transcription. The findings facilitate a better understanding of the processes governing the HIV-1 lifecycle. The multicolor labeling protocol developed in this study may find many applications involving virus-host-cell interactions. PMID- 27253588 TI - Interleukin 6 modulates PPARalpha and PGC-1alpha and is involved in high-fat diet induced cardiac lipotoxicity in mouse. AB - BACKGROUND: Interleukin 6 (IL-6) may be involved in regulation of cardiac lipid metabolism and mitochondrial function through its influence on peroxisome proliferator-activated receptors (PPARs). In this study we evaluated the impact of the physiological level of IL-6 on the expression of PPARalpha and PGC-1alpha in the heart and the effect of lack of this cytokine on high-fat diet (HFD) induced lipotoxicity. METHODS: Male C57BL6/J wild type (WT) and IL-6 knock-out (IL-6KO) mice were used. 20 animals of each genotype were fed with HFD for 15 18weeks. Cardiac function was assessed using echocardiography and cardiomyocyte ultrastructure was examined using electron microscopy. QT-PCR and Western blotting were applied to estimate the expression of PPARalpha and PGC-1alpha at the transcriptional and protein levels. RESULTS: At baseline WT and IL-6KO mice had similar size and function of the left ventricle. HFD induced similar left ventricular hypertrophic response in both groups without causing heart failure, but only WT animals had increased resting ejection fraction of the LV. Ultrastructure of HFD groups showed markers of lipotoxicity, that were more pronounced in IL-6KO group. In basal conditions IL-6KO animals had lower PPARalpha and similar PGC-1alpha expression as compared to WT. HFD induced downregulation of both PPARalpha and PGC-1alpha in WT animals, while in IL-6KO mice this effect was constrained. CONCLUSION: IL-6 is involved in basal regulation of PPARalpha and PGC-1alpha expression in cardiomyocytes. The lack of this cytokine promotes high-fat diet induced lipotoxicity but without overt manifestations of cardiac failure. PMID- 27253589 TI - Organizational culture of a private hospital. AB - Objective To assess the values and practices that characterize the organizational culture of a private hospital in the state of Sao Paulo in the perspective of nursing professionals. Methods Quantitative, descriptive, cross-sectional study. Data collection was conducted between January and March 2013 using the Brazilian Instrument for Assessing Organizational Culture. Twenty-one nurses and sixty-two nursing aides and technicians participated in the study. The responses of the participants were coded into numerical categories, generating an electronic database to be analyzed by means of the software Statistical Package for the Social Sciences. Results Scores of cooperative professionalism values (3.24); hierarchical strictness values (2.83); individual professionalism values (2.69); well-being values (2.71); external integration practices (3.73); reward and training practices (2.56); and relationship promotion practices (2.83). Conclusion In the perception of workers, despite the existence of hierarchical strictness there is cooperation at work and the institution pursues customer satisfaction and good interpersonal relationships. PMID- 27253590 TI - Difficulties and challenges in reviewing ethical aspects of research in Brazil. AB - Objective To reflect on the problems faced by researchers from different areas, especially of Humanities and Social Sciences, when submitting research projects for evaluation by the research ethics committees in Brazil. Method A theoretical and reflective study based on international literature and the critical analysis of the authors. Results Although Resolution 466/2012, which addresses human research, contains some innovations, issues related to the research participants remain obscure and the project evaluation process is time-consuming. Conclusion The difficulties faced by researchers, especially in the fields of Humanities and Social Sciences, must be transposed to ensure that the ethical guidelines are applicable, in terms of principles and procedures, to the different research traditions. Appropriate human research standards must be managed by a system with a satisfactory operational capacity, according to the specificities of the different areas of knowledge. PMID- 27253591 TI - Representations of nurses and individuals in psychological distress in the photographic exhibit USAnatomy, by Steven Klein. AB - Objectives To analyze the representations of the nurse and individual in mental suffering portrayed in the photographic work by Steven Klein, in the USAnatomy exhibit held at the Museum of Sculpture (Museu da escultura) in Sao Paulo, in 2011. Methods Qualitative study carried out in 2012. Three photographs were submitted to iconographic analysis. The interpretation of the findings was based on theoretical frameworks of Foucault and Bourdieu on power relations. Results The nurse is represented as a sensual, insensitive person, with the power to control and torture while the person in psychological distress is represented as dirty, imprisoned and subjected to an asymmetrical relationship of power with the nurse. Final considerations Relationships of submission and symbolic dominance, in which the person in psychological distress has their body molded by discipline imposed by the nurse. Stereotypes of the image of the nurse oppose the ideology of the profession, which is to ensure the integrity of those being cared for. PMID- 27253592 TI - Factors associated with the deaths of men poisoned by carbamato ("chumbinho"). AB - Objective To determine the factors associated with death in poisoning victims by carbamate ("Chumbinho"). Method Retrospective study, epidemiological case-control based on poisoning reporting forms, a poison control center located in the metropolitan region of Rio de Janeiro. We used 24 notification forms of poisoning in men aged 20 to 59 years with poisoning by carbamate history from 2005 to 2009. The records were randomly selected, respecting the ratio 1:3 (a case to three controls). The age range was 23-58 years, average 43.83 years. Results The most frequent symptoms were myosis (OR=1.0; 95% CI: 0.27 to 3.69 p=1.0.), drooling (OR=0.83; 95% CI. 0.22 to 3.12 p=0.78), and dyspnea (OR=0.66; 95% CI: 0:14-3.03 p=0.59). Conclusion The deaths were associated with drooling, miosis and dyspnea and a strong association with pulmonary rales, bronchospasm and pulmonary snoring. PMID- 27253593 TI - Nursing interventions and outcomes classifications in patients with wounds: cross mapping. AB - Objective Cross-mapping of terms referring to nursing interventions and outcomes in the medical records of patients with wounds compared to nursing interventions and nursing outcomes classifications. Method An observational retrospective study based on cross-mapping. The sample consisted of 81 outpatients treated in a university hospital in Rio de Janeiro. Data was collected from medical records between May and July of 2013. The analysis was done in four steps: search for phrases used to describe interventions and outcomes; setting the frequency of occurrence of phrases; grouping synonyms; comparison of terms with taxonomies. Results 13 interventions were mapped and the most frequent was "Care with wounds" (47.23%). Also, 6 results were mapped and the priority was "Wound healing: secondary intention" (45%). Conclusions The use of cross-mapping of terms referring to interventions and nursing outcomes in patients with wounds suggested additions to the taxonomies for adaptation to outpatient care. PMID- 27253594 TI - Quality of life of undergraduate nursing students. AB - Objective The aim of this paper is to analyse the quality of life (QOL) of undergraduate nursing students. Methods A descriptive cross-sectional study with 206 students conducted in July 2013, in the city of Picos/PI, Brazil. Data were collected using the WHOQOL-BREF questionnaire. The Mann-Whitney and Kruskal Wallis tests were used to analyse the data with a significance level of 5%. Results The domains with the best average scores were Physical (69.4) and Social Relations (74.3), and the domains with the worst average scores were Psychological (68.5) and Environment (54.2). For the overall assessment, the average was 66.6+10.8. A statistical significance was observed when crossing QOL with number of children (p = 0.029), where students without children performed better. Conclusion These results allow the early detection of difficulties experienced by nursing students and may support strategies that benefit the search for solutions to conflicts that affect QOL. PMID- 27253595 TI - Leadership in nursing and patient satisfaction in hospital context. AB - Objectives to know the quality of the leadership relationship from the perspective of a chief nurse and nurse, patient satisfaction, the relationship between the quality of the relationship perceived for both and patient satisfaction. Methods a quantitative, transverse and correlational approach. Non probabilistic convenience sample consists of 15 chief nurses, 342 nurses, 273 patients. Data collected at the Central Lisbon Hospital Center, between January and March 2013, through the LMX-7, CLMX-7 and SUCEH21 scales. Statistical analysis was performed through SPSS (r) Statistics 19. Results the chief nurse considers the quality of the leadership relationship good, the nurses consider it satisfactory, patients are considered to be satisfied with nursing care; there is a statistically significant correlation between the quality of the leadership relationship from the perspective of chief nurses and patient satisfaction, there is no statistically significant correlation between the quality of the leadership relationship in the nurse's perspective and satisfaction. Conclusion the chief nurse has a major role in patient satisfaction. PMID- 27253596 TI - Cases of violence involving transvestites and transsexuals in a northeastern Brazilian city. AB - Objective To analyze cases of violence against transvestites and transsexuals based on their sociodemographic profile. Method Cross-sectional, descriptive research performed in Cajazeiras / Paraiba, consisting of 16 transvestites and transsexuals. Data collection took place in April 2014 and was analyzed descriptively. Results The typology of violence that victimized transvestites and transsexuals were: verbal (91.96%), psychological (58.33%) and physical (33.33%), often between 24 hours and six months preceding the survey. Regarding the spatiality: the street, school and health services were all scenarios of aggression. With respect to the offending agent, the findings point towards neighbors, family members and health professionals. All forms of violence happened between agents and spaces of aggression. Conclusions Violence among this population, silence around the situations of abuse became more pronounced as did its invisibility in the social and institutional context, reflecting the inhibition of human rights and concealment of reality. PMID- 27253597 TI - Reasons and consequences of low adherence to standard precautions by the nursing team. AB - Standard precautions (SP) are recommendations to prevent infection and protect health care workers during the provision of care, however, still exists low adherence to these recommendations. Objective To analyze the reasons and consequences of low adherence to standard precautions by the nursing staff. Method integrative literature review, search in seven databases, from 2005 to 2014. Results 30 articles were selected for analysis. The reasons for low adherence evidenced relate to deficient practices of lifelong learning, risk behaviors of workers, inadequate provision of equipment and protective equipment and inadequate working conditions. The consequences are accidents and occupational diseases. There are few intervention studies, which merely provide guidance to professionals. Conclusions The low adhesion to standard precautions is linked to individual aspects of workers, employers and educational institutions. Intervention strategies carried out have shown little efficient by only focusing on the worker. PMID- 27253598 TI - Contribution of structured therapeutic play in a nursing care model for hospitalised children. AB - Objective To analyse how therapeutic play structured in a nursing care model contributes to the care of hospitalised children. Method This is a qualitative study based on convergent care research (CCR). Seven children participated in the study. Data were collected in September and October of 2014 by means of interviews with open-end questions and participant observation of therapeutic and dramatic play sessions and/or instructional play sessions based on the stages "Welcoming/Playing/Concluding" of the nursing model Care with Play. Data were analysed according to the analysis and interpretation stages of the CCR. Results The following three categories emerged: Meanings attributed by the child to hospitalisation and its influence on nursing care; Perception of the therapeutic procedures through therapeutic play, and Importance of the family in care. Final considerations It is concluded that the application of therapeutic play structured in the care model contributes to systematic and specialised nursing care. PMID- 27253599 TI - Contributions of the sandwich doctoral program to methodological approaches: an experience report. AB - Objective To share our experience on theoretical and methodological insights we have gained as researchers working together during the Sandwich Doctoral Program. Method This is a descriptive experience report. Results We have incorporated restoration thinking into a study on patient safety culture and will enhance knowledge translation by applying principles of deliberative dialogue to increase the uptake and implementation of research results. Conclusion Incorporating new approaches in Brazilian nursing research plays a key role in achieving international participation and visibility in different areas of nursing knowledge. PMID- 27253600 TI - Genesis of home care in Brazil at the start of the twentieth century. AB - Objective to discuss the conditions that enabled home care at the beginning of the twentieth century. Method study of the genealogic inspiration on home care. The empirical material consisted of legal documents on the subject that were published in the Official Journal. The documents were studied using analytical tools, such as Power, Discipline and Biopolitics, which were inspired in Foucault. Results two analytical categories were established, "home inspection: visiting nurses and tuberculosis" and "records: political and economic apparatus". Final considerations tuberculosis, the new profession of visiting nurses, inspection records and the detailed analysis of the cities grant home care a nature of surveillance, inspection and control to conduct the behaviour of individuals. PMID- 27253601 TI - Nursing work environment, patient safety and quality of care in pediatric hospital. AB - Objectives To describe the characteristics of the nursing work environment, safety attitudes, quality of care, measured by the nursing staff of the pediatric units, as well as to analyze the evolution of quality of care and hospital indicators. Methods Descriptive study with 136 nursing professionals at a paediatric hospital, conducted through personal and professional characterization form, Nursing Work Index - Revised, Safety Attitudes Questionnaire - Short Form 2006 and quality indicators. Results The professionals perceive the environment as favourable to professional practice, and consider good quality care that is also observed by reducing the incidence of adverse events and decreased length of stay. The domain job satisfaction was considered favourable to patient safety. Conclusions The work environment is favourable to nursing practice, the professionals nursing approve the quality of care and the indicators tended reducing adverse events and length of stay. PMID- 27253602 TI - Hypertensive patients in primary health care: access, connection and care involved in spontaneous demands. AB - Objective To assess the impacts of inclusion of care for spontaneous demands in the treatment of hypertensive patients in primary health care. Methods Third generation qualitative assessment survey conducted with 16 workers in a Primary Care Health Unit (PHCU) of the city of Fortaleza, state of Ceara, in the period between July and September of 2015. To collect data, systematic field observation and semi-structured interviews were used, and the stages of thematic content analysis were adopted for data analysis. Results Participants revealed that access, connection and care are fundamental to the treatment of hypertension. However, they said that the introduction of free access for spontaneous demands compromised the flow of care in the hypertension programs. Conclusion A dichotomy between the practice of care recommended by health policies and the one existing in the reality of PHCUs was shown, causing evident losses to the care of hypertensive patients in primary care. PMID- 27253603 TI - Laminated Graphene Films for Flexible Transparent Thin Film Encapsulation. AB - We introduce a simple, inexpensive, and large-area flexible transparent lamination encapsulation method that uses graphene films with polydimethylsiloxane (PDMS) buffer on polyethylene terephthalate (PET) substrate. The number of stacked graphene layers (nG) was increased from 2 to 6, and 6 layered graphene-encapsulation showed high impermeability to moisture and air. The graphene-encapsulated polymer light emitting diodes (PLEDs) had stable operating characteristics, and the operational lifetime of encapsulated PLEDs increased as nG increased. Calcium oxidation test data confirmed the improved impermeability of graphene-encapsulation with increased nG. As a practical application, we demonstrated large-area flexible organic light emitting diodes (FOLEDs) and transparent FOLEDs that were encapsulated by our polymer/graphene encapsulant. PMID- 27253605 TI - Investigation of the bipolar effect in the thermoelectric material CaMg2Bi2 using a first-principles study. AB - The bipolar effect in relatively narrow band-gap thermoelectric (TE) compounds is a negative process deteriorating the TE properties particularly at higher temperatures. In this work, we investigate the TE performance of the compound CaMg2Bi2 using the first-principles calculation and semi-classical Boltzmann transport theory in combination with our experimental data. It is revealed that this compound exhibits a remarkable bipolar effect and temperature-dependent carrier concentration. The bipolar effect imposes remarkable influence on all the electron-transport related TE parameters. An effective carrier concentration neff as a function of temperature is proposed to account for the bipolar effect induced carrier excitations. The as-evaluated TE parameters then show good consistency with measured results. This work may shed light on our understanding of the bipolar effect in TE compounds. PMID- 27253604 TI - Stepwise Evolution of Coral Biomineralization Revealed with Genome-Wide Proteomics and Transcriptomics. AB - Despite the importance of stony corals in many research fields related to global issues, such as marine ecology, climate change, paleoclimatogy, and metazoan evolution, very little is known about the evolutionary origin of coral skeleton formation. In order to investigate the evolution of coral biomineralization, we have identified skeletal organic matrix proteins (SOMPs) in the skeletal proteome of the scleractinian coral, Acropora digitifera, for which large genomic and transcriptomic datasets are available. Scrupulous gene annotation was conducted based on comparisons of functional domain structures among metazoans. We found that SOMPs include not only coral-specific proteins, but also protein families that are widely conserved among cnidarians and other metazoans. We also identified several conserved transmembrane proteins in the skeletal proteome. Gene expression analysis revealed that expression of these conserved genes continues throughout development. Therefore, these genes are involved not only skeleton formation, but also in basic cellular functions, such as cell-cell interaction and signaling. On the other hand, genes encoding coral-specific proteins, including extracellular matrix domain-containing proteins, galaxins, and acidic proteins, were prominently expressed in post-settlement stages, indicating their role in skeleton formation. Taken together, the process of coral skeleton formation is hypothesized as: 1) formation of initial extracellular matrix between epithelial cells and substrate, employing pre-existing transmembrane proteins; 2) additional extracellular matrix formation using novel proteins that have emerged by domain shuffling and rapid molecular evolution and; 3) calcification controlled by coral-specific SOMPs. PMID- 27253606 TI - Current indications for pegging in the anophthalmic socket: are there any? AB - PURPOSE OF REVIEW: To highlight the development, problems, and current status of coupling porous orbital implants to the overlying prosthetic eye. RECENT FINDINGS: Although increasing the risk of complications, pegging significantly contributes to prosthesis motility and satisfies the cosmetic expectations of some patients. Patients should be counseled regarding the increased risks in approximately one-third of individuals and that complications can occur even 10 years following implantation. SUMMARY: Although implant peg placement has declined dramatically over the past decade, a precise and meticulous technique under intravenous anesthesia in the appropriately selected patient can be a successful outpatient procedure. Fortunately, most problems are of a minor nature, and over 85% of patients are able to retain their pegs following proper management and timely intervention. Additional visits to the ophthalmic plastic surgeon or ocularist are required that may not be necessary if a peg had not been placed. PMID- 27253607 TI - Conjunctivodacryocystorhinostomy with Jones tube: a history and update. AB - PURPOSE OF REVIEW: Current opinions and trends in the management of upper lacrimal obstruction include design variations on the original Lester Jones tube and updated awareness and management of the problems associated with the tubes. This article includes a brief review of the fascinating history of the development of the Jones tube, which sets the perspective for the current scientific dialog. RECENT FINDINGS: First, many design modifications have been proposed to reduce the risk of tube migration and extrusion, with no consensus on the best tube. Second, the issue of retrograde airflow through the Jones tube with the use of continuous positive airway pressure is an increasingly common and challenging problem. Third, bacterial biofilms on the surface of the Jones tube can play a role in recalcitrant infections. Jones tubes can be cleaned or replaced in the office setting with topical anesthesia. SUMMARY: Conjunctivodacryocystorhinostomy (CDCR) with placement of a Jones tube remains the gold standard for management of upper lacrimal obstruction. This article provides an updated perspective on issues with extrusion or migration of the tube, bothersome retrograde airflow with the use of a continuous positive airway pressure device, and management of crusting and possible infectious biofilms on the tube. PMID- 27253608 TI - Obstacle Crossing Differences Between Blind and Blindfolded Subjects After Haptic Exploration. AB - Little is known about the ability of blind people to cross obstacles after they have explored haptically their size and position. Long-term absence of vision may affect spatial cognition in the blind while their extensive experience with the use of haptic information for guidance may lead to compensation strategies. Seven blind and 7 sighted participants (with vision available and blindfolded) walked along a flat pathway and crossed an obstacle after a haptic exploration. Blind and blindfolded subjects used different strategies to cross the obstacle. After the first 20 trials the blindfolded subjects reduced the distance between the foot and the obstacle at the toe-off instant, while the blind behaved as the subjects with full vision. Blind and blindfolded participants showed larger foot clearance than participants with vision. At foot landing the hip was more behind the foot in the blindfolded condition, while there were no differences between the blind and the vision conditions. For several parameters of the obstacle crossing task, blind people were more similar to subjects with full vision indicating that the blind subjects were able to compensate for the lack of vision. PMID- 27253609 TI - Corrigendum: Universal lineshapes at the crossover between weak and strong critical coupling in Fano-resonant coupled oscillators. PMID- 27253610 TI - Quantitative Fundus Autofluorescence in Early and Intermediate Age-Related Macular Degeneration. AB - IMPORTANCE: Increased lipofuscin accumulation is assumed to be an important factor in the pathogenesis of age-related macular degeneration (AMD), although direct evidence for this hypothesis is missing. OBJECTIVE: To quantitatively investigate lipofuscin-associated fundus autofluorescence (AF) in patients with early and intermediate AMD. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single-center, case-control study was conducted from August 1, 2014, to October 31, 2015, at a university referral center. Participants included 40 patients aged 65 years or younger and 108 individuals without eye disease serving as controls. All participants underwent quantitative fundus AF (qAF) imaging with a modified scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF values of an 8-segment circular ring centered on the fovea (qAF8) were measured and compared between patients and controls. For subgroup analysis, drusen were categorized as soft drusen, cuticular drusen, and/or reticular pseudodrusen (RPD). MAIN OUTCOMES AND MEASURES: The qAF8 levels. RESULTS: In the 40 patients with AMD, mean (SD) age was 54.8 (5.6) years, and 32 (80%) were women. None of the investigated patients had qAF8 values above the 95% prediction interval (PI) of the 108 controls. In the soft drusen (28 [70%]) and cuticular drusen (8 [20%]) groups, qAF8 levels within the 95% PI were noted in 22 patients (79%; 95% CI, 60% to 90%) and 7 patients (88%; 95% CI, 51% to 99%) respectively. The qAF8 values in the RPD group (4 [10%]) were below the 95% PI in 3 patients (75%; 95% CI, 29% to 97%). Compared with the controls, statistical analysis revealed lower qAF8 values in the overall AMD cohort after adjusting for age (difference, -19.9% [95% CI, -25.6% to -12.7%], P < .001) as well as in all subgroups (soft drusen, -17.1% [95% CI, -24.1% to -9.5%], P < .001; cuticular drusen, -19.6% [95% CI, -30.3% to -7.2%], P = .003; and RPD, -34.5% [95% CI, 47.1% to -21.3%]; P < .001). CONCLUSIONS AND RELEVANCE: The qAF8 measurements in this sample showed no increased lipofuscin-related fundus AF in patients with early and intermediate AMD. Lower qAF levels in certain subgroups may point to subnormal lipofuscin levels in the retinal pigment epithelium or, alternatively, limitations to detection of true retinal pigment epithelial lipofuscin content. The results of this study might expand the understanding of the pathogenesis of AMD and may have an effect on upcoming treatment trials that aim to modify lipofuscin accumulation. PMID- 27253612 TI - Improved resiliency and well-being among military personnel in a Swedish Naval Force after a counter-piracy operation off the coast of Somalia. AB - The aim of this study was to explore: (1) how the psychological health of the members of the first European Union Naval Force (ME01) was affected by international deployment off the coast of Somalia; and (2) if and how organizational and personal factors (e.g., type of personnel category, previous experiences, and resilience) affected their psychological health and well-being post-deployment. The study had an exploratory longitudinal design, where the participants were assessed both before and after deployment (i.e., T1 and T2). The participants (n = 129, 120 men, 9 women) were equally distributed between officers (n = 68; 64 men, 4 women) and sailors (n = 61; 56 men, 5 women). The members' average age was 31 years, ranging from 20 to 61. For the majority (78%) ME01 was their first international deployment and officers were, in general, more experienced than sailors. The overall results showed that the members' reported a positive experience with improved resilience and well-being (e.g., sense of coherence). However, the result also showed that type of personnel category (i.e., officer or sailor) affected their psychological health. Why and how these differences among military personnel arise is discussed, but deserves further attention. PMID- 27253611 TI - Enzymatic Process for High-Yield Turanose Production and Its Potential Property as an Adipogenesis Regulator. AB - Turanose is a sucrose isomer naturally existing in honey and a promising functional sweetener due to its low glycemic response. In this study, the extrinsic fructose effect on turanose productivity was examined in Neisseria amylosucrase reaction. Turanose was produced, by increasing the amount of extrinsic fructose as a reaction modulator, with high concentration of sucrose substrate, which resulted in 73.7% of production yield. In physiological functionality test, lipid accumulation in 3T3-L1 preadipocytes in the presence of high amounts of pure glucose was attenuated by turanose substitution in a dose dependent manner. Turanose treatments at concentrations representing 50%, 75%, and 100% of total glucose concentration in cell media significantly reduced lipid accumulation by 18%, 35%, and 72%, respectively, as compared to controls. This result suggested that turanose had a positive role in controlling adipogenesis, and enzymatic process of turanose production has a potential to develop a functional food ingredient for controlling obesity and related chronic diseases. PMID- 27253613 TI - Genome Editing with Engineered Nucleases in Economically Important Animals and Plants: State of the Art in the Research Pipeline. AB - After induced mutagenesis and transgenesis, genome editing is the next step in the development of breeding techniques. Genome editing using site-directed nucleases - including meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR/Cas9 system - is based on the mechanism of double strand breaks. The nuclease is directed to cleave the DNA at a specific place of the genome which is then repaired by natural repair mechanisms. Changes are introduced during the repair that are either accidental or can be targeted if a DNA template with the desirable sequence is provided. These techniques allow making virtually any change to the genome including specific DNA sequence changes, gene insertion, replacements or deletions with unprecedented precision and specificity while being less laborious and more straightforward compared to traditional breeding techniques or transgenesis. Therefore, the research in this field is developing quickly and, apart from model species, multiple studies have focused on economically important species and agronomically important traits that were the key subjects of this review. In plants, studies have been undertaken on disease resistance, herbicide tolerance, nutrient metabolism and nutritional value. In animals, the studies have mainly focused on disease resistance, meat production and allergenicity of milk. However, none of the promising studies has led to commercialization despite several patent applications. The uncertain legal status of genome-editing methods is one of the reasons for poor commercial development, as it is not clear whether the products would fall under the GMO regulation. We believe this issue should be clarified soon in order to allow promising methods to reach their full potential. PMID- 27253614 TI - Reply. PMID- 27253615 TI - Visualization of electrical field of electrode using voltage-controlled fluorescence release. AB - In this study we propose an approach to directly visualize electrical current distribution at the electrode-electrolyte interface of a biopotential electrode. High-speed fluorescent microscopic images are acquired when an electric potential is applied across the interface to trigger the release of fluorescent material from the surface of the electrode. These images are analyzed computationally to obtain the distribution of the electric field from the fluorescent intensity of each pixel. Our approach allows direct observation of microscopic electrical current distribution around the electrode. Experiments are conducted to validate the feasibility of the fluorescent imaging method. PMID- 27253616 TI - Dynamic frequency feature selection based approach for classification of motor imageries. AB - Electroencephalography (EEG) is one of the most popular techniques to record the brain activities such as motor imagery, which is of low signal-to-noise ratio and could lead to high classification error. Therefore, selection of the most discriminative features could be crucial to improve the classification performance. However, the traditional feature selection methods employed in brain computer interface (BCI) field (e.g. Mutual Information-based Best Individual Feature (MIBIF), Mutual Information-based Rough Set Reduction (MIRSR) and cross validation) mainly focus on the overall performance on all the trials in the training set, and thus may have very poor performance on some specific samples, which is not acceptable. To address this problem, a novel sequential forward feature selection approach called Dynamic Frequency Feature Selection (DFFS) is proposed in this paper. The DFFS method emphasized the importance of the samples that got misclassified while only pursuing high overall classification performance. In the DFFS based classification scheme, the EEG data was first transformed to frequency domain using Wavelet Packet Decomposition (WPD), which is then employed as the candidate set for further discriminatory feature selection. The features are selected one by one in a boosting manner. After one feature being selected, the importance of the correctly classified samples based on the feature will be decreased, which is equivalent to increasing the importance of the misclassified samples. Therefore, a complement feature to the current features could be selected in the next run. The selected features are then fed to a classifier trained by random forest algorithm. Finally, a time series voting-based method is utilized to improve the classification performance. Comparisons between the DFFS-based approach and state-of-art methods on BCI competition IV data set 2b have been conducted, which have shown the superiority of the proposed algorithm. PMID- 27253617 TI - Automated screening system for retinal health using bi-dimensional empirical mode decomposition and integrated index. AB - Posterior Segment Eye Diseases (PSED) namely Diabetic Retinopathy (DR), glaucoma and Age-related Macular Degeneration (AMD) are the prime causes of vision loss globally. Vision loss can be prevented, if these diseases are detected at an early stage. Structural abnormalities such as changes in cup-to-disc ratio, Hard Exudates (HE), drusen, Microaneurysms (MA), Cotton Wool Spots (CWS), Haemorrhages (HA), Geographic Atrophy (GA) and Choroidal Neovascularization (CNV) in PSED can be identified by manual examination of fundus images by clinicians. However, manual screening is labour-intensive, tiresome and time consuming. Hence, there is a need to automate the eye screening. In this work Bi-dimensional Empirical Mode Decomposition (BEMD) technique is used to decompose fundus images into 2D Intrinsic Mode Functions (IMFs) to capture variations in the pixels due to morphological changes. Further, various entropy namely Renyi, Fuzzy, Shannon, Vajda, Kapur and Yager and energy features are extracted from IMFs. These extracted features are ranked using Chernoff Bound and Bhattacharyya Distance (CBBD), Kullback-Leibler Divergence (KLD), Fuzzy-minimum Redundancy Maximum Relevance (FmRMR), Wilcoxon, Receiver Operating Characteristics Curve (ROC) and t test methods. Further, these ranked features are fed to Support Vector Machine (SVM) classifier to classify normal and abnormal (DR, AMD and glaucoma) classes. The performance of the proposed eye screening system is evaluated using 800 (Normal=400 and Abnormal=400) digital fundus images and 10-fold cross validation method. Our proposed system automatically identifies normal and abnormal classes with an average accuracy of 88.63%, sensitivity of 86.25% and specificity of 91% using 17 optimal features ranked using CBBD and SVM-Radial Basis Function (RBF) classifier. Moreover, a novel Retinal Risk Index (RRI) is developed using two significant features to distinguish two classes using single number. Such a system helps to reduce eye screening time in polyclinics or community-based mass screening. They will refer the patients to main hospitals only if the diagnosis belong to the abnormal class. Hence, the main hospitals will not be unnecessarily crowded and doctors can devote their time for other urgent cases. PMID- 27253618 TI - Finite element analysis of left ventricle during cardiac cycles in viscoelasticity. AB - To investigate the effect of myocardial viscoeslasticity on heart function, this paper presents a finite element model based on a hyper-viscoelastic model for the passive myocardium and Hill's three-element model for the active contraction. The hyper-viscoelastic model considers the myocardium microstructure, while the active model is phenomenologically based on the combination of Hill's equation for the steady tetanized contraction and the specific time-length-force property of the myocardial muscle. To validate the finite element model, the end-diastole strains and the end-systole strain predicted by the model are compared with the experimental values in the literature. It is found that the proposed model not only can estimate well the pumping function of the heart, but also predicts the transverse shear strains. The finite element model is also applied to analyze the influence of viscoelasticity on the residual stresses in the myocardium. PMID- 27253619 TI - A computational approach to mortality prediction of alcohol use disorder inpatients. AB - BACKGROUND: Health information technologies can assist clinicians in the Intensive Care Unit (ICU) by providing additional analysis of patient stability. However, because patient diagnoses can be confounded by chronic alcohol use, the predictive value of existing systems is suboptimal. Through the use of Electronic Health Records (EHR), we have developed computer software called AutoTriage to generate accurate predictions through multi-dimensional analysis of clinical variables. We analyze the performance of AutoTriage on the Alcohol Use Disorder (AUD) subpopulation in this study, and build on results we reported for AutoTriage performance on the general population in previous work. METHODS: AUD related ICD-9 codes were used to obtain a patient population from MIMIC III ICU dataset for a retrospective study. Patient mortality risk score is generated through analysis of eight EHR-based clinical variables. The score is determined by combining weighted subscores, each of which are obtained from singlets, doublets or triplets of one or more of the eight continuous-valued clinical variable inputs. A temporally updating risk score is computed with a continuously revised 12-hour mortality prediction. RESULTS: Among AUD patients, in a non overlapping test set, AutoTriage outperforms existing systems with an Area Under Receiver Operating Characteristic (AUROC) value of 0.934 for 12-h mortality prediction. At a sensitivity of 90%, AutoTriage achieves a specificity of 80%, positive predictive value of 40%, negative predictive value of 89%, and an Odds Ratio of 36. CONCLUSIONS: For mortality prediction, AutoTriage demonstrates improvements in both the accuracy and the Odds Ratio over current systems among the AUD patient population. PMID- 27253620 TI - Association and Diffusion of Li(+) in Carboxymethylcellulose Solutions for Environmentally Friendly Li-ion Batteries. AB - Carboxymethylcellulose (CMC) has been proposed as a polymeric binder for electrodes in environmentally friendly Li-ion batteries. Its physical properties and interaction with Li(+) ions in water are interesting not only from the point of view of electrode preparation-processability in water is one of the main reasons for its environmental friendliness-but also for its possible application in aqueous Li-ion batteries. We combine molecular dynamics simulations and variable-time pulsed field gradient spin-echo (PFGSE) NMR spectroscopy to investigate Li(+) transport in CMC-based solutions. Both the simulations and experimental results show that, at concentrations at which Li-CMC has a gel-like consistency, the Li(+) diffusion coefficient is still very close to that in water. These Li(+) ions interact preferentially with the carboxylate groups of CMC, giving rise to a rich variety of coordination patterns. However, the diffusion of Li(+) in these systems is essentially unrestricted, with a fast, nanosecond-scale exchange of the ions between CMC and the aqueous environment. PMID- 27253621 TI - Attentional cueing induces false memory. AB - The fluency of stimulus processing significantly contributes to recognition memory judgments. We investigated the effect of processing fluency induced by attentional cueing on recognition judgments. Participants performed a Remember/Know recognition test, while their spatial attention was manipulated in the test session. Stimulus location was either predicted (congruent condition) or unpredicted (incongruent condition) using an arrow cue. The results revealed that familiarity-based false recognition increased in the incongruent condition wherein the participants may have attributed part of the perceived disfluency to the attentional cue, and they may have overestimated the fluency for the stimulus, leading to increased false recognition. However, in the congruent condition, the participants may have attributed some parts of the perceived fluency to the attentional cue and underestimated the fluency for the stimulus, leading to decreased false recognition. In sum, stimulus-irrelevant attentional cueing induces unintentional processing about the source of fluency and biases recognition memory. PMID- 27253622 TI - Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugates Provide Very Long-Acting Octreotide. AB - We developed a long-acting drug-delivery system that supports subcutaneous administration of the peptidic somatostatin agonist octreotide-a blockbuster drug used to treat acromegaly and neuroendocrine tumors. The current once-a-month polymer-encapsulated octreotide, Sandostatin LAR, requires a painful intragluteal injection through a large needle by a health-care professional. To overcome such shortcomings, Tetra-PEG hydrogel microspheres were covalently attached to the alpha-amine of d-Phe(1) or the epsilon-amine of Lys(5) of octreotide by a self cleaving beta-eliminative linker; upon subcutaneous injection in the rat using a small-bore needle, octreotide was slowly released. The released drug from the epsilon-octreotide conjugate showed a remarkably long serum half-life that exceeded two months. The alpha-octreotide conjugate had a half-life of ~2 weeks, and showed an excellent correlation of in vitro and in vivo drug release. Pharmacokinetic models indicate these microspheres should support once-weekly to once-monthly self-administered subcutaneous dosing in humans. The hydrogel octreotide conjugate shows the favorable pharmacokinetics of Sandostatin LAR without its drawbacks. PMID- 27253623 TI - Discovery of the first small-molecule CsrA-RNA interaction inhibitors using biophysical screening technologies. AB - AIM: CsrA is a global post-transcriptional regulator protein affecting mRNA translation and/or stability. Widespread among bacteria, it is essential for their full virulence and thus represents a promising anti-infective drug target. Therefore, we aimed at the discovery of CsrA-RNA interaction inhibitors. Results & methodology: We followed two strategies: a screening of small molecules (A) and an RNA ligand-based approach (B). Using surface plasmon resonance-based binding and fluorescence polarization-based competition assays, (A) yielded seven small molecule inhibitors, among them MM14 (IC50 of 4 uM). (B) resulted in RNA-based inhibitor GGARNA (IC50 of 113 uM). CONCLUSION: The first small-molecule inhibitors of the CsrA-RNA interaction were discovered exhibiting micromolar affinities. These hits represent tools to investigate the effects of CsrA-RNA interaction inhibition on bacterial virulence. PMID- 27253624 TI - Correlation between anti-JC-virus and anti-cytomegalovirus, -Epstein-Barr virus and -measles/-rubella/-varicella-zoster-virus antibodies. AB - Anti-JCV antibody status is used for PML-risk-stratification in MS patients before and during Natalizumab therapy. JCV antibodies can be detected in around 60% of MS patients, however, only a small proportion actually develop PML. As anti-viral antibodies tend to occur unspecifically, the aim of this study was to correlate JCV antibody status and index with other common anti-viral antibodies. A total of 123 samples of MS-patients were tested for anti-JCV antibodies by JCV Stratify-ELISA at Unilabs, Denmark. The same samples were analyzed for measles, rubella, varicella zoster, EBV, and CMV IgG and IgM antibodies by ELISA, or chemiluminescence-microparticle immunoassay. For all antibody-titers correlations were calculated and group comparisons of JCV-positive and -negative patients were performed. Fifty-three patients (43.1%) were JCV negative and 70 (56.9%) positive. CMV-IgM antibodies were detected in six patients. Otherwise no IgM antibodies were detected. IgG antibodies against measles, rubella, varicella zoster, and EBV were detected in >=97% of patients and 47 samples (38.2%) tested positive for CMV-IgG. There was no significant correlation between any of the antibody titers including JCV index, however, a significantly higher prevalence (P = 0.003) of CMV-IgG in JCV positive compared to JCV negative patients, whereas no difference was detected for measles, rubella, varicella zoster, and EBV IgG. In conclusion, the JCV antibody response in MS patients seems to be largely independent of any other anti-viral immunity. The only coincidence was found with CMV IgG antibodies which might point towards some immunological cross-reactivity in anti-viral immune response or other mechanisms leading to combined viral infections such as shared transmission. J. Med. Virol. 89:3-9, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27253625 TI - Exposure of Somatic Cells to Cytoplasm Extracts of Porcine Oocytes Induces Stem Cell-Like Colony Formation and Alters Expression of Pluripotency and Chromatin Modifying Genes. AB - Cell permeabilization followed by exposure to cytoplasmic extracts of oocytes has been proposed as an alternative to transduction of transcription factors for inducing pluripotency in cultured somatic cells. The main goal in this study was to investigate the effect of treating porcine fibroblast cells with cytoplasmic extracts of GV-stage oocyte (OEx) followed by inhibition of histone deacetylases with Scriptaid (Scrip) on the formation of stem cell-like colonies and expression of genes encoding pluripotency and chromatin-modifying enzymes. Stem cell-like colonies start developing ~2 weeks after treatment in cells exposed to OEx or OEx + Scrip. The number of cell colonies at the first day of appearance and 48 hours later was also similar between OEx and OEx + Scrip treatments. Transcripts for Nanog, Rex1, and c-Myc genes were detected in most cell samples that were analyzed on different days after OEx treatment. However, Sox2 transcripts were not detected and only a small proportion of samples had detectable levels of Oct4 mRNA after OEx treatment. A similar pattern of transcripts for pluripotency genes was observed in cells treated with OEx alone or OEx + Scrip. Transcript levels for Dnmt1 and Ezh2 were reduced at Day 3 after treatment in cells exposed to OEx. These findings revealed that: (a) exposure to OEx can induce a partial reprogramming of fibroblast cells toward pluripotency, characterized by colony formation and activation of pluripotency genes; and (b) inhibition of histone deacetylases does not improve the reprogramming effect of OEx treatment. PMID- 27253626 TI - Phenotypes of Aging Postovulatory Oocytes After Somatic Cell Nuclear Transfer in Mice. AB - Oocytes rapidly lose their developmental potential after ovulation, termed postovulatory oocyte aging, and often exhibit characteristic phenotypes, such as cytofragmentation, abnormal spindle shapes, and chromosome misalignments. Here, we reconstructed mouse oocytes using somatic cell nuclear transfer (SCNT) to reveal the effect of somatic cell-derived nuclei on oocyte physiology during aging. Normal oocytes started undergoing cytofragmentation 24 hours after oocyte collection; however, this occurred earlier in SCNT oocytes and was more severe at 48 hours, suggesting that the transferred somatic cell nuclei affected oocyte physiology. We found no difference in the status of acetylated alpha-tubulin (Ac Tub) and alpha-tubulin (Tub) between normal and SCNT aging oocytes, but unlike normal oocytes, aging SCNT oocytes did not have astral microtubules. Interestingly, aging SCNT oocytes displayed more severely scattered chromosomes or irregularly shaped spindles. Observations of the microfilaments showed that, in normal oocytes, there was a clear actin ring beneath the plasma membrane and condensed microfilaments around the spindle (the actin cap) at 0 hours, and the actin filaments started degenerating at 1 hour, becoming completely disrupted and distributed to the cytoplasm at 24 hours. By contrast, in SCNT oocytes, an actin cap formed around the transplanted nuclei within 1 hour of SCNT, which was still present at 24 hours. Thus, SCNT oocytes age in a similar but distinct way, suggesting that they not only contain nuclei with abnormal epigenetics but are also physiologically different. PMID- 27253627 TI - Improvement of Chicken Primordial Germ Cell Maintenance In Vitro by Blockade of the Aryl Hydrocarbon Receptor Endogenous Activity. AB - Primordial germ cells (PGCs) are the undifferentiated progenitors of gametes. Germline competent PGCs can be developed as a cell-based system for genetic modification in chickens, which provides a valuable tool for transgenic technology with both research and industrial applications. This implies manipulation of PGCs, which, in recent years, encouraged a lot of research focused on the study of PGCs and the way of improving their culture. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that besides mediating toxic responses to environmental contaminants plays pivotal physiological roles in various biological processes. Since a novel compound that acts as an antagonist of this receptor has been reported to promote expansion of hematopoietic stem cells, we conducted the present study with the aim of determining whether addition of an established AHR antagonist to the standard culture medium used nowadays for in vitro chicken PGCs culture improves ex vivo expansion. We have found that addition of alpha-naphthoflavone in culture medium promotes the amplification of undifferentiated cells and that this effect is exerted by the blockade of AHR action. Our results constitute the first report of the successful use of a readily available AHR antagonist to improve avian PGCs expansion, and they further extend the knowledge of the effects of AHR modulation in undifferentiated cells. PMID- 27253628 TI - Effects of Activin in Embryoid Bodies Expressing Fibroblast Growth Factor 5. AB - Nodal/activin signaling is indispensable for embryonic development. We examined what activin does to the embryoid bodies (EBs) produced from mouse embryonic stem cells (mESCs) expressing an epiblast marker. The EBs were produced by culturing mESCs by the hanging drop method for 24 hours. The resulting EBs were transferred onto gelatin-coated dishes and allowed to further differentiate. The 24-hour EBs showed a stronger expression of fibroblast growth factor (FGF)5 and Brachyury (specific to the epiblast) in comparison with mESCs. Treating the transferred EBs with activin A maintained transcript levels of FGF5 and Oct4, while inhibiting definitive endoderm differentiation. The activin A treatment reversed the endoderm differentiation induced by retinoic acid (RA), while the inhibition of nodal/activin signaling promoted RA-induced endoderm differentiation. Inhibition of nodal/activin signaling in EBs, including epiblast-like cells, promotes differentiation into the endoderm, facilitating the transition from the pluripotent state to specification of the endoderm. PMID- 27253629 TI - Cell Synchronization by Rapamycin Improves the Developmental Competence of Porcine SCNT Embryos. AB - The cell cycle stage of donor cells influences the success of somatic cell nuclear transfer (SCNT). This study investigated the effects of rapamycin treatment on synchronization of porcine fibroblasts in comparison with control and serum-starved cells, SCNT donor cell viability, and SCNT-derived embryo development. Porcine fibroblasts were treated with 0.1, 1, 10, and 100 MUM rapamycin for 1 or 3 days. The proportion of cells in G0/G1 phase was significantly higher among cells treated with 1 MUM rapamycin for 3 days (D3-1R) than among control and serum-starved cells (p < 0.05). In comparison with control cells, rapamycin-treated cells exhibited reduced proliferation, similar to serum starved cells. The viability (as assessed by the MTT assay) of D3-1R-treated cells was good, similar to control cells, showing their quality was maintained. To confirm nutrient regulation by rapamycin treatment, we checked the transcript levels of nutrient transporter genes (SLC2A2, SLC2A4, SLC6A14, and SLC7A1). These levels were significantly lower in D3-1R-treated cells than in control cells (p < 0.01). We performed SCNT with D3-1R-treated cells (SCNT(D3-1R)) to confirm the effect of cell cycle synchronization by rapamycin treatment. Although SCNT(D3-1R) embryos did not have an increased fusion rate, their cleavage and blastocyst formation rates were significantly higher than those of control embryos (p < 0.05). Regarding embryo quality, the numbers of total and apoptotic cells per blastocyst were increased and decreased, respectively, in SCNT(D3-1R) blastocysts. The mRNA levels of developmental (CDX2 and CDH1) and proapoptotic (FAS and CASP3) genes were significantly higher and lower, respectively, in SCNT(D3-1R) blastocysts than in control blastocysts (p < 0.05). These results demonstrate that rapamycin treatment affects the cell cycle synchronization of donor cells and enhances the developmental potential of porcine SCNT embryos. PMID- 27253630 TI - Human Rabies - Wyoming and Utah, 2015. AB - In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk. PMID- 27253631 TI - A novel miR-203-DNMT3b-ABCG2 regulatory pathway predisposing colorectal cancer development. AB - Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. The majority of studies to date focused on genetic mutations and epigenetic changes that drive the CRC carcinogenesis process. Xenobiotic transporters play an important role in safeguarding our body from external toxic substances. These transporters lining the gastrointestinal tract protect us from dietary carcinogens. This study aimed to investigate the downregulation of an efflux transporter ABCG2 in CRC versus normal colon mucosa, so as to shed light on its relevance to CRC initiation and progression. We found that ABCG2 expression is at least 50-fold lower in adenomatous polyps and colon carcinoma specimens obtained from CRC patients than in their matched pair of adjacent normal colon mucosa. The underlying mechanism(s) for ABCG2 under-expression in CRC is currently not known. To this end, aberrant promoter methylation of ABCG2 has been reported to cause its repression in a few cancer types including renal carcinoma and multiple myeloma. In this study, miR-203 was found to be downregulated in all polyps and CRC specimens, relative to adjacent normal colon mucosa. We demonstrated that the de novo DNA methyltransferase DNMT3b is a direct target of miR-203. Importantly, by relieving the repression on DNMT3b, the lower expression of miR-203 in CRC caused ABCG2 promoter methylation and remarkable lower ABCG2 expression in colon cancer cell lines and the patient CRC specimens. The restoration of ABCG2 function via modulating this new microRNA-methylation mechanism in precancerous cells may represent an attractive strategy to delay the carcinogenesis process. (c) 2016 Wiley Periodicals, Inc. PMID- 27253632 TI - Effect of ethyleneoxide groups of anionic surfactants on lipase activity. AB - The use of enzymes in laundry and dish detergent products is growing. Such tendency implies dedicated studies to understand surfactant-enzyme interactions. The interactions between surfactants and enzymes and their impact on the catalytic efficiency represent a central problem and were here evaluated using circular dichroism, dynamic light scattering, and enzyme activity determinations. This work focuses on this key issue by evaluating the role of the ethyleneoxide (EO) groups of anionic surfactants on the structure and activity of a commercial lipase, and by focusing on the protein/surfactant interactions at a molecular level. The conformational changes and enzymatic activity of the protein were evaluated in the presence of sodium dodecyl sulfate (SDS also denoted as SLE0 S) and of sodium lauryl ether sulfate with two EO units (SLE2 S). The results strongly suggest that the presence of EO units in the surfactant polar headgroup determines the stability and the activity of the enzyme. While SDS promotes enzyme denaturation and consequent loss of activity, SLE2 S preserves the enzyme structure and activity. The data further highlights that the electrostatic interactions among the protein groups are changed by the presence of the adsorbed anionic surfactants being such absorption mainly driven by hydrophobic interactions. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1276-1282, 2016. PMID- 27253634 TI - Cost of hospitalisation for non-communicable diseases in India: are we pro-poor? AB - OBJECTIVES: To estimate out-of-pocket (OOP) expenditure due to hospitalisation from NCDs and its impact on households in India. METHODS: The study analysed nationwide representative data collected by the National Sample Survey Organisation in 2014 that reported health service utilisation and healthcare related OOP expenditure by income quintiles and by type of health facility (public or private). The recall period for inpatient hospitalisation expenditure was 365 days. Consumption expenditure was collected for a recall period of 1 month. OOP expenditure amounting to >10% of annual consumption expenditure was termed as catastrophic. Weighted analysis was performed. RESULTS: The median expenditure per episode of hospitalisation due to NCDs was USD 149 - this was ~3 times higher among the richest quintile compared to poorest quintile. There was a significantly higher prevalence of catastrophic expenditure among the poorest quintile, more so for cancers (85%), psychiatric and neurological disorders (63%) and injuries (63%). Mean private-sector OOP hospitalisation expenditure was nearly five times higher than that in the public sector. Medicines accounted for 40% and 27% of public- and private-sector OOP hospitalisation expenditure, respectively. CONCLUSION: Strengthening of public health facilities is required at community level for the prevention, control and management of NCDs. Promotion of generic medicines, better availability of essential drugs and possible subsidisation for the poorest quintile will be measures to consider to reduce OOP expenditure in public-sector facilities. PMID- 27253633 TI - Low Lean Mass Predicts Incident Fractures Independently From FRAX: a Prospective Cohort Study of Recent Retirees. AB - Whether low muscle mass predisposes to fracture is still poorly understood. In the diagnosis of sarcopenia, different thresholds for low lean mass have been proposed but comparative data for these criteria against hard outcomes such as fractures are lacking. This study aimed to investigate the prevalence of low lean mass according to different thresholds used in operational definitions of sarcopenia and their association with 3-year fracture incidence in a cohort of healthy 63- to 67-year-old community dwellers. In a longitudinal analysis of 913 participants (mean age 65.0 +/- 1.4 years) enrolled in the Geneva Retirees Cohort (GERICO) study, lean mass was assessed by dual-energy X-ray absorptiometry (DXA), and low trauma clinical fracture incidence was recorded over a 3-year period. Prevalence of low lean mass ranged from 3.5% to 20.2% according to the threshold applied. During a follow-up of 3.4 +/- 0.9 years, 40 (4.4%) participants sustained at least one low trauma fracture. After multivariate adjustment including Fracture Risk Assessment Tool (FRAX) probability with femoral neck bone mineral density (BMD), low lean mass, as defined by Baumgartner thresholds, was associated with higher fracture risk (odds ratio [OR], 2.32; 95% CI, 1.04 to 5.18; p = 0.040). It also added significant predictive value beyond FRAX (likelihood ratio test for nested models, 4.28; p < 0.039). No significant association was found for other definition thresholds. The coexistence of sarcopenia and a T-score <-2.5 at spine or hip was associated with a 3.39-fold (95% CI, 1.54 to 7.46; p = 0.002) increase in low trauma fracture risk. In conclusion, low lean mass, as defined by the Baumgartner thresholds, is a predictor of incident fractures in a large cohort of healthy 65-year-old community dwellers, independently of FRAX probability. The increased risk is related to the threshold for low lean mass selected. These findings suggest that identification of sarcopenia should be considered in fracture risk assessment beyond usual risk factors. (c) 2016 American Society for Bone and Mineral Research. PMID- 27253635 TI - Flexible Roles for American Indian Elders in Community-Based Participatory Research. AB - Community-based participatory research builds partnerships between communities and academic researchers to engage in research design, decision making, data collection, and dissemination of health promotion initiatives. Community-based participatory projects often have formal agreements or defined roles for community and academic partners. Our project (November 2012-November 2014) was designed to document life narratives of urban American Indian elders as a foundation for developing a resilience-based health promotion curriculum for urban American Indian adolescents aged 12 to 18. We used a flexible method for engaging community partners that honored the individual strengths of elders, encouraged them to describe how they wanted to contribute to the project, and provided multiple ways for elders to engage with university partners. We invited elders to participate in one or more of the following roles: as members of consensus panels to develop interview questions, as members of a community advisory board, or as participants in individual qualitative interviews. The flexibility of roles gave elders the opportunity to serve as advisors, co developers, interviewees, or reviewers during 2 years of curriculum development. Engaging American Indian elders in the research process acknowledged the multiple layers of expertise they had as traditional leaders in the community while promoting trust in and ownership of the project. This flexible technique can be used by other communities that may not be comfortable with structured processes of engagement. PMID- 27253636 TI - Community Interagency Connections for Immigrant Worker Health Interventions, King County, Washington State, 2012-2013. AB - INTRODUCTION: Cross-sector community partnerships are a potentially powerful strategy to address population health problems, including health disparities. US immigrants - commonly employed in low-wage jobs that pose high risks to their health - experience such disparities because of hazardous exposures in the workplace. Hazardous exposures contribute to chronic health problems and complicate disease management. Moreover, prevention strategies such as worksite wellness programs are not effective for low-wage immigrant groups. The purpose of this article was to describe an innovative application of social network analysis to characterize interagency connections and knowledge needed to design and deliver a comprehensive community-based chronic disease prevention program for immigrant workers. METHODS: Using iterative sample expansion, we identified 42 agencies representing diverse community sectors (service agencies, faith-based organizations, unions, nonprofits, government agencies) pertinent to the health of Chinese immigrant workers. To capture data on shared information, resources, and services as well as organizational characteristics, we jointly interviewed 2 representatives from each agency. We used social network analysis to describe interagency network structure and the positions of agencies within the networks. RESULTS: Agency interconnections were established primarily for information sharing. In the overall interagency network, a few service-oriented agencies held central or gatekeeper positions. Strong interconnectedness occurred predominately across service, public, and nonprofit sectors. The Chinese and Pan-Asian service sectors showed the strongest interconnectedness. CONCLUSION: Network analysis yields critical understanding of community structural links and assets needed to inform decisions about actual and potential community collaborations. Alternative intervention strategies may be needed to address health disparities among immigrant workers. PMID- 27253637 TI - Trends in Early Childhood Obesity in a Large Urban School District in the Southwestern United States, 2007-2014. AB - INTRODUCTION: Although recent studies indicate that rates of childhood obesity and severe obesity may be declining, few studies have reported prevalence trends in early childhood or differences in trends across sociodemographic groups. The primary aim of this study was to report trends in prevalence of early childhood obesity and severe obesity 2007 through 2014 in a diverse, metropolitan school district in the southwestern United States and determine whether these trends vary by race/ethnicity, socioeconomic status, and disability status. METHODS: We analyzed height, weight and demographic data from 43,113 kindergarteners enrolled in a large, urban school district in the southwestern United States for 7 school years. Adjusted odds of obesity and severe obesity were calculated to assess changes in prevalence for non-Hispanic white, Hispanic, and American Indian students; free or reduced-price lunch participants and nonparticipants; and students with and without disabilities. To test for differences in obesity trends, interaction terms were added to the logistic regressions between school year and sex, race/ethnicity, free or reduced-price lunch participation, and disability status. RESULTS: The adjusted prevalence of both obesity (from 13.1% in 2007-2008 to 12.0% in 2013-20014) and severe obesity (from 2.4% in 2007-2008 to 1.2% in 2013-2014) declined overall. We found no significant interactions between the adjusted prevalence of obesity over time and any of the sociodemographic subgroups. Obesity prevalence declined more among American Indian students than among Hispanic or non-Hispanic white students. CONCLUSION: In this district, from 2007 through 2014, severe obesity decreased and obesity did not increase, overall and across all sociodemographic subpopulations for kindergarten students. PMID- 27253638 TI - Sustained Release of Cx43 Antisense Oligodeoxynucleotides from Coated Collagen Scaffolds Promotes Wound Healing. AB - Antisense oligodeoxynucleotides targeting the mRNA of the gap junction protein Cx43 promote tissue repair in a variety of different wounds. Delivery of the antisense drug has most often been achieved by a thermoreversible hydrogel, Pluronic F-127, which is very effective in the short term but does not allow for sustained delivery over several days. For chronic wounds that take a long time to heal, repeated dosing with the drug may be desirable but is not always compatible with conventional treatments such as the weekly changing of compression bandages on venous leg ulcers. Here the coating of collagen scaffolds with antisense oligonucleotides is investigated and a way to provide protection of the oligodeoxynucleotide drug is found in conjunction with sustained release over a 7 d period. This approach significantly reduces the normal foreign body reaction to the scaffold, which induces an increase of Cx43 protein and an inhibition of healing. As a result of the antisense integration into the scaffold, inflammation is reduced with the rate of wound healing and contracture is significantly improved. This coated scaffold approach may be very useful for treating venous leg ulcers and also for providing a sustained release of any other types of oligonucleotide drugs that are being developed. PMID- 27253639 TI - Palladium-Zeolite nanofiber as an effective recyclable catalyst membrane for water treatment. AB - Zeolite is an exciting natural material due to its unique capability of ammonium nitrogen (NH3N) adsorption in water. In this study, multifunctional hybrid composites of zeolite/palladium (Ze/Pd) on polymer nanofiber membranes were fabricated and explored for sustainable contaminant removal. SEM and XRD demonstrated that zeolite and palladium nanoparticles were uniformly distributed and deposited on the nanofibers. NH3N recovery rate was increased from 23 to 92% when palladium coated zeolite was embedded on the nanofiber. Multifunctional nanofibers of Ze/Pd membranes were able to adsorb NH3N on the zeolites placed on the surface of fibers and palladium catalysts were capable of selective oxidation of NH3N to N2 gas. The cycling of NH3N adsorption-oxidation, high flux, hydrophilicity, and flexibility of the membrane makes it a strong candidate for water treatment. PMID- 27253651 TI - Ventricular Tachycardia: A Rare Commotio Cordis Presentation. AB - Commotio cordis is a rare event caused by an unfortunately timed blunt anterior chest wall impact that most commonly presents in young male adolescents and is the second leading cause of death in young athletes. The most common initial presenting dysrhythmias are ventricular fibrillation and asystole, although other rare dysrhythmias have been reported-predominantly in animal models. To our knowledge, this is the first telemetry-confirmed case of commotio cordis with a presenting cardiac rhythm of ventricular tachycardia. While prompt recognition of commotio cordis and early cardiopulmonary resuscitation and defibrillation (if applicable) are still the treatment in these cases, our case offers potential insight into the underlying commotio cordis process. PMID- 27253652 TI - Predicting Flow in the Pediatric Emergency Department: Are Holidays Lighter? AB - OBJECTIVE: The aim of this study was to determine whether patient volume in an urban pediatric emergency department (ED) can be predicted based on holidays and thus aid in staffing and resource allocation. METHODS: Log-in dates and times were obtained for all patients seen in an urban pediatric ED between July 1, 2006, and June 30, 2013. Visits were coded for the day of the week, tour (ie, shift), and season and whether they occurred on a holiday or nonholiday. Comparisons between the median number of patient visits on holidays versus nonholidays by day of the week, tour, and season were performed. Additional comparisons on 5 Monday holidays as well as New Year's Day, Thanksgiving, and Christmas Day were also performed. Data were presented as medians with interquartile ranges. Group comparisons were performed via using Mann-Whitney U tests and Kruskal-Wallis tests (alpha = 0.05, 2 tailed). RESULTS: There were 223,677 total patient visits, with a mean yearly census of 31,954. The median daily volume was 85, peaking on Mondays (median, 99). The summer season demonstrated the fewest number of patient visits (median, 74) relative to the other seasons (medians, 89-91). Compared with nonholidays, there were fewer patient visits on Thanksgiving and Christmas Day and in the late afternoon and evening on other individual holidays. CONCLUSIONS: Fewer patient visits on Thanksgiving and Christmas Days, as well as during the late afternoon/evening on several other holidays, point to the possibility of small adjustments to staffing in ways that can more efficiently balance demand with available resources. PMID- 27253653 TI - Pediatric Airway Management and Prehospital Patient Safety: Results of a National Delphi Survey by the Children's Safety Initiative-Emergency Medical Services for Children. AB - OBJECTIVE: The objective of this study was to determine what aspects of prehospital pediatric airway management may contribute to patient safety events. METHODS: We conducted a 3-phase Delphi survey in prehospital professionals across the United States to identify potential contributors to patient safety events. Respondents ranked how likely factors were to contribute on a 9-point Likert-type scale and were allowed to elaborate through open-ended questions. Analysis was conducted using a mixed-methods approach, including Likert-type responses and open-ended questions which were analyzed for specific themes. RESULTS: All 3 phases of the survey were completed by 492 participants; 50.8% of respondents were paramedics, 22% were emergency medical technician-basics/first responders, and 11.4% were physicians. Seventy-five percent identified lack of experience with advanced airway management, and 44% identified medical decision making regarding airway interventions as highly likely to lead to safety events. Within the domain of technical skills, advanced airway management was ranked in the top 3 contributors to safety events by 71% of participants, and bag-mask ventilation by 18%. Qualitative analysis of questions within the domains of equipment and technical skills identified endotracheal intubation as the top contributor to safety events, with bag-mask ventilation second. In the domains of assessment and decision making, respiratory assessment and knowing when to perform an advanced airway were ranked most highly. CONCLUSIONS: This national Delphi survey identified lack of experience with pediatric airway management and challenges in decision making in advanced airway management as high risk for safety events, with endotracheal intubation as the most likely of these. PMID- 27253654 TI - Outcomes After Pediatric Out-of-Hospital Cardiopulmonary Interventions. AB - OBJECTIVE: The aim of the study was to evaluate outcomes after pediatric out-of hospital cardiopulmonary interventions (CPIs) by emergency medical services (EMS). METHODS: Children (age, <=18 years) who received CPI by EMS from 2001 to 2008 were identified from the Utah Department of Health. Cardiopulmonary intervention was defined as oxygenation, ventilation or CPR, and transport to a hospital by EMS. Univariate and multivariable regression analyses evaluated associations between potential predictors and outcomes (death and new neurologic dysfunction). RESULTS: A total of 464 patients (58% male) received EMS attention. For the 71% patients (327) who were alive on EMS arrival, 63% (205) received CPI without CPR. Of note, 6% (12) of these patients died after arrival to the hospital and new neurologic dysfunction was diagnosed in 6% (13). Among the 12 patients who died, 50% (6) were younger than 1 year.On multivariable regression analysis, factors associated with increased risk of death before and in-hospital are the following: age younger than 1 year (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.17-0.39), shorter EMS transport time (OR, 0.94; 95% CI, 0.89 0.99), and longer EMS dispatch time (OR, 1.23; 95% CI, 1.08-1.40). Factors associated with increased risk of new neurologic dysfunction are the following: lack of pulse (OR, 0.14; 95% CI, 0.04-0.53), requiring CPR (OR, 6.15; 95% CI, 1.48-25.6), and CPR duration (OR, 1.20; 95% CI, 1.05-1.37). CONCLUSIONS: Age younger than 1 year, shorter transport time, and longer dispatch time were associated with increased risk of death. Being pulseless upon discovery and receiving CPR were associated with new neurologic dysfunction. Maximizing EMS transport interventions for patients younger than 1 year requiring CPI may improve patient outcomes. PMID- 27253655 TI - Methemoglobinemia Following Monolinuron Ingestion: A Case Report in a Child. AB - CASE: We describe a case report of a 2-year-old boy presenting to the emergency department with cyanosis and agitation. There was no suggestive history of poisoning but parents reported the presence of an aquarium at the family dinner the night before, with an aquarium cleaner beside it. Physical examination at admission revealed central cyanosis without signs of respiratory distress. Oxygen saturation measured by pulse oximetry (SpO2) was at 80% in room air. Plasma level of methemoglobin was measured at 11.8%. After 6 hours, methemoglobin decreased spontaneously to 5% and pulse oximetry saturation reached 98% in room air. Consciousness, weakness, and behavior were concomitantly improved. Because of rapid and spontaneous improvement, no specific treatment such as methylene blue was administered. A mass spectrometry toxicological analysis was performed in a blood sample taken the day of admission. Screening procedure of pesticides based on liquid chromatography coupled with mass spectrometry identified monolinuron, a phenylurea herbicide. CONCLUSIONS: We recommend considering acquired methemoglobinemia after ingestion of industrial products and drugs in children with cyanosis, mental status alteration, and without respiratory distress symptoms. PMID- 27253656 TI - Trauma Arrest and Spinal Injury in a 3-Year-Old Girl. AB - Management of an acutely injured pediatric patient with multiple traumas is a common challenge facing clinicians in pediatric emergency care. Blunt trauma is more common in the pediatric population with motor vehicle accidents being the most common cause of injury. Spinal injury, especially in young children, is only seen in 1% to 2% of cases and can be lethal. It is incumbent upon clinicians to be able to meet the challenges of patient management including airway management, providing hemodynamic support, and addressing potentially reversible causes of arrest while recognizing presenting symptoms of spinal injury. This case presents a child in trauma arrest after a motor vehicle crash requiring advanced interventions, diagnostics, and support. Her clinical course is described and reveals a complete distraction of the cervical and thoracic spine. This case illustrates pathology and management along with the importance of proper management and interventions by pediatric emergency clinicians to manage the patient and attempt to maximize the patient's outcome. PMID- 27253657 TI - Are We Adequately Treating Pain in Children Who Present to US Emergency Departments?: Factors That Contribute to Pain Treatment in Pediatric Patients. AB - OBJECTIVES: There are no recent national data on analgesic use for pain treatment in children. Our objective was to determine if there is adequate pain treatment for children in US emergency departments (EDs) and determine predictors of nonopioid and opioid analgesic administration. METHODS: Children younger than 18 years with the diagnosis of extremity fracture, appendicitis, or urinary tract stones were obtained from the National Health Ambulatory Medical Care Survey (NHAMCS) (2006-2010) and analyzed using logistic regression for complex samples. There were 2 analyses: (1) those who received analgesics versus those who did not; and (2) of those who received analgesics, opioid versus nonopioid analgesic use. RESULTS: There were 1341 records analyzed representing 4.5 million ED visits. Those who received analgesics were more likely to be older than age of 3 years (P = 0.05), be discharged from the hospital (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.04-2.94), arrive between noon and midnight (OR, 0.1.85; CI, 1.12-3.03), and have a higher pain rating (P < 0.01). Children who received opioid analgesics were more likely to live outside the Northeast (P = 0.04), require admission (OR, 2.95; CI, 1.09-7.98), have a higher acuity triage level (OR, 1.79; CI, 1.04-3.06), have higher pain scores (P < 0.01), and have private insurance (OR, 1.75; CI, 1.06-2.94). CONCLUSIONS: There is still a lot of room for improvement of pediatric pain control in US EDs. We aim to apply this information toward direct physician and nursing education interventions, including the recognition of age appropriate pain cues, and parental information and guidance to improve pediatric pain treatment in US EDs. PMID- 27253658 TI - Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study. AB - Suvorexant is a dual orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia at a maximum dose of 20 mg. This randomized double-blind crossover study evaluated the abuse potential of suvorexant in 36 healthy recreational polydrug users with a history of sedative and psychedelic drug use. Single doses of suvorexant (40, 80, and 150 mg: 2-7.5 * maximum dose), zolpidem (15 and 30 mg: 1.5-3 * maximum dose), and placebo were administered, with a 10-day washout between treatments. Subjective and objective measures, including visual analog scales (VASs), Addiction Research Center Inventory, and cognitive/psychomotor tests, were evaluated for 24-hour postdose. Suvorexant had significantly greater peak effects on "drug liking" VAS (primary endpoint) than placebo. Although effects of suvorexant on abuse potential measures were generally similar to zolpidem, they remained constant across doses, whereas zolpidem often had greater effects at higher doses. Suvorexant (all doses) had significantly fewer effects than zolpidem 30 mg on secondary measures, such as "high" VAS, Bowdle VAS, and Addiction Research Center Inventory morphine benzedrine group. The overall incidence of abuse-related adverse events, such as euphoric mood and hallucination, was numerically lower with suvorexant than zolpidem. In agreement with its classification as a schedule IV drug, suvorexant demonstrated abuse potential, compared with placebo. The abuse potential was similar to zolpidem using certain measures, but with a reduced incidence of abuse related adverse events. Although this suggests that the overall abuse liability of suvorexant may be lower than zolpidem, the actual abuse rates will be assessed with the postmarketing experience. PMID- 27253660 TI - A New Formulation of Oral Viscous Budesonide in Treating Paediatric Eosinophilic Oesophagitis: A Pilot Study. AB - OBJECTIVES: Oral viscous budesonide is a recent therapeutic option for eosinophilic oesophagitis (EoE) compared with dietary restriction and inhaled steroids. This single-centre, open-label, not blinded study aims to evaluate the efficacy and safety of a new, preprepared oral viscous budesonide suspension (PVB) in children and adolescents with EoE. METHODS: We treated 36 children with PVB (29 boys; median age 12 years) with EoE diagnosed according to European Society for Paediatric Gastroenterology Hepatology and Nutrition guidelines. Patients <150 and >150 cm height received 2 and 4 mg PVB daily, respectively, for 12 weeks. Upper gastrointestinal endoscopy was performed at baseline, after 12 weeks of therapy and 24 weeks after the end of therapy. Baseline and post treatment scores were calculated for symptoms, endoscopy, and histology. Serum cortisol was performed at baseline, 12, and 36 weeks. RESULTS: At the end of PVB trial, endoscopy showed macroscopic remission in 32 patients (88.9%), whereas at histology median pre- and post-treatment peak eosinophil count/high power field (HPF) markedly decreased from 42.2 (range: 15-100) to 2.9 (range: 0-30); moreover, mean symptom and histology scores impressively improved compared with baseline (P < 0.01). At 24 weeks after the end of PVB therapy, endoscopy showed oesophageal relapse in 21 patients (58.3%), whereas 15 (41.7%) were still in remission. Seven children (19.4%) with positive multichannel intraluminal impedance-pH were treated also with proton pump inhibitors. No significant difference between pre-/post-treatment morning cortisol levels occurred. CONCLUSIONS: The new PVB suspension presented in the present study is effective and safe for treating children with proven EoE. Larger placebo-controlled clinical trials would provide more information about dosing, efficacy, and long term safety of this formulation, specifically designed for the oesophagus. PMID- 27253661 TI - Pediatric Crohn Disease Clinical Outcome Assessments and Biomarkers: Current State and Path Forward for Global Collaboration. AB - OBJECTIVE: There is a pressing need for drug development in pediatric Crohn disease (CD). Our aim was to provide strategic approaches toward harmonization of current thinking about clinical outcome assessments (COAs) and biomarkers to facilitate drug development in pediatric CD. METHODS: Scientists from the United States Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan had monthly teleconferences from January 2014 through May 2015. A literature review was conducted to assess the measurement properties of all existing COA tools and to evaluate the current landscape of biomarkers used in pediatric CD. Based on the findings of literature review, we reached the consensus on the strategic approaches for evaluating outcomes in pediatric CD trials. RESULTS: The pediatric Crohn's Disease Activity Index, Crohn's Disease Activity Index, and Harvey Bradshaw's index were used in pediatric CD clinical studies. But they lack adequate measurement properties (validity, reliability, and ability to detect change of the treatment) that are required to support approval of products intended to treat pediatric CD. Biomarkers (ie, fecal lactoferrin, osteoprotegerin, and calprotectin) have shown some promise for their potential as noninvasive surrogate endpoints in CD. CONCLUSIONS: Lack of well-defined and reliable COAs presents a hurdle for global drug development in pediatric CD. It is essential to develop well-defined and reliable COAs that can measure meaningful clinical benefit for patients in terms of how they feel, function, and survive. Development of noninvasive biomarkers as reliable surrogate endpoints needs to be further explored. PMID- 27253662 TI - Deficiency in Mucosa-associated Lymphoid Tissue Lymphoma Translocation 1: A Novel Cause of IPEX-Like Syndrome. AB - OBJECTIVE: Early-onset inflammatory bowel diseases can result from a wide spectrum of rare mendelian disorders. Early molecular diagnosis is crucial in defining treatment and in improving life expectancy. Herein we aimed at defining the mechanism of an immunodeficiency-polyendrocrinopathy and enteropathy-X-linked (IPEX)-like disease combined with a severe immunodeficiency in 2 siblings born from distantly related parents. METHODS: Whole exome sequencing was performed on blood-extracted genomic DNA from the 2 affected children and their parents on the genomic platform of Institut IMAGINE. Candidate gene mutation was identified using the in-house software PolyWeb and confirmed by Sanger sequencing. Protein expression was determined by western blot. Flow cytometry was used to assess consequences of the mutation on lymphocyte phenotype and nuclear factor-kappa B (NF-kappaB) activation at diagnosis and after treatment by hematopoietic stem cell transplantation. RESULTS: We identified a homozygous missense mutation in mucosa-associated lymphoid tissue lymphoma translocation 1 gene (MALT1), which precluded protein expression. In keeping with the known function of MALT1, NF kappaB-dependent lymphocyte activation was severely impaired. Moreover, there was a drastic reduction in Forkhead box P3 (FOXP3) regulatory T cells accounting for the IPEX-like phenotype. Following identification of the mutation, both children received hematopoietic stem cell transplantation, which permitted full clinical recovery. Immunological workup at 6 and 12 months after transplantation showed normal NF-kappaB activation and correction of regulatory T cells frequency. CONCLUSIONS: Along with FOXP3, interleukin 2 receptor alpha chain (IL2RA), and cytotoxic T-lymphocyte protein 4 precursor (CTLA-4) mutations, MALT1 deficiency should now be considered as a possible cause of IPEX-like syndrome associated with immunodeficiency that can be cured by hematopoietic stem cell transplantation. PMID- 27253663 TI - Aeroallergens in Eosinophilic Esophagitis: Significant Triggers or Noise in the System? PMID- 27253665 TI - Testicular Receptor-4: Novel Regulator of Glucocorticoid Resistance. AB - CONTEXT: Glucocorticoids are powerful steroid hormones that regulate development, metabolism, and immune response. However, glucocorticoid unresponsiveness or resistance is observed in the treatment of inflammatory, autoimmune, and lymphoproliferative diseases and significantly limits their efficacy. OBJECTIVE: In Cushing's disease, although some glucocorticoid-mediated suppression of pituitary-derived ACTH is seen, corticotroph tumors exhibit relative resistance to glucocorticoid action. We previously demonstrated that testicular orphan receptor 4 (TR4) binds to the pro-opiomelanocortin (POMC) promoter to induce corticotroph tumor POMC expression and ACTH secretion, and we hypothesized that TR4 may interact with glucocorticoid signaling to modulate POMC expression and action. RESULTS: Here we demonstrate that TR4 abrogates glucocorticoid receptor (GR)- or dexamethasone-mediated POMC and activator protein-1 transrepression in both murine and human pituitary corticotroph tumor cells. Co-immunoprecipitation studies indicate that TR4 and GR interact directly with each other, resulting in TR4-mediated disruption of GR binding to the POMC promoter. CONCLUSION: These results demonstrate that TR4 binds GR to play an important role in glucocorticoid directed corticotroph tumor POMC regulation in addition to modulating glucocorticoid actions on other GR targets. Characterization of this pathway may offer important insights into glucocorticoid resistance and may identify a novel approach for the treatment of Cushing's disease and the glucocorticoid-resistant states. PMID- 27253664 TI - Rapid Proteasomal Degradation of Mutant Proteins Is the Primary Mechanism Leading to Tumorigenesis in Patients With Missense AIP Mutations. AB - CONTEXT: The pathogenic effect of mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene (AIPmuts) in pituitary adenomas is incompletely understood. We have identified the primary mechanism of loss of function for missense AIPmuts. OBJECTIVE: This study sought to analyze the mechanism/speed of protein turnover of wild-type and missense AIP variants, correlating protein half life with clinical parameters. DESIGN AND SETTING: Half-life and protein-protein interaction experiments and cross-sectional analysis of AIPmut positive patients' data were performed in a clinical academic research institution. PATIENTS: Data were obtained from our cohort of pituitary adenoma patients and literature reported cases. INTERVENTIONS: Protein turnover of endogenous AIP in two cell lines and fifteen AIP variants overexpressed in HEK293 cells was analyzed via cycloheximide chase and proteasome inhibition. Glutathione-S-transferase pull down and quantitative mass spectrometry identified proteins involved in AIP degradation; results were confirmed by coimmunoprecipitation and gene knockdown. Relevant clinical data was collected. MAIN OUTCOME MEASURES: Half-life of wild type and mutant AIP proteins and its correlation with clinical parameters. RESULTS: Endogenous AIP half-life was similar in HEK293 and lymphoblastoid cells (43.5 and 32.7 h). AIP variants were divided into stable proteins (median, 77.7 h; interquartile range [IQR], 60.7-92.9 h), and those with short (median, 27 h; IQR, 21.6-28.7 h) or very short (median, 7.7 h; IQR, 5.6-10.5 h) half-life; proteasomal inhibition rescued the rapid degradation of mutant proteins. The experimental half-life significantly correlated with age at diagnosis of acromegaly/gigantism (r = 0.411; P = .002). The FBXO3-containing SKP1-CUL1-F-box protein complex was identified as the E3 ubiquitin-ligase recognizing AIP. CONCLUSIONS: AIP is a stable protein, driven to ubiquitination by the SKP1-CUL1-F box protein complex. Enhanced proteasomal degradation is a novel pathogenic mechanism for AIPmuts, with direct implications for the phenotype. PMID- 27253666 TI - Nonalcoholic Fatty Liver Disease Is Associated With Coronary Artery Calcification Development: A Longitudinal Study. AB - CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown. OBJECTIVE: This study investigated the longitudinal association between NAFLD and CAC score. DESIGN AND SETTING: This study is a longitudinal cohort study performed in a healthcare center. PARTICIPANTS: Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography. MAIN OUTCOME MEASURES: CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed. RESULTS: More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P < .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose dependently associated with the development of CAC (P for trend = .043). CONCLUSIONS: NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors. PMID- 27253667 TI - Complex Genomic Rearrangement Within the GNAS Region Associated With Familial Pseudohypoparathyroidism Type 1b. AB - CONTEXT: Pseudohypoparathyroidism type 1b (PHP-1b) results from methylation defects at the G protein stimulatory alpha subunit (GNAS) exon A/B-differentially methylated region (DMR). Although microduplications in the GNAS region were recently identified in two PHP-1b patients, genetic information on these patients remained fragmentary. CASE DESCRIPTION: A 20-year-old Japanese male and his mother presented with hypocalcemia and elevated blood levels of intact PTH. The proband had a maternal uncle who was previously diagnosed with PHP-1b. Methylation-specific multiplex ligation-dependent probe amplification, array based comparative genomic hybridization, pyrosequencing, fluorescence in situ hybridization, and whole-genome sequencing were performed for this family. The proband, mother, and uncle carried maternally derived approximately 133-kb duplication-triplication-duplication rearrangements at 20q13.32 involving NESP55, NESPAS, XLalphas, and exon A/B-DMR but not STX16 or the Gsalpha coding region. These individuals exhibited partial methylation defects of NESP55-, NESPAS-, and XLalphas-DMRs, which were ascribable to the increased copy numbers of these regions retaining the maternally derived methylation pattern and loss of methylation of exon A/B-DMR, which was inexplicable by the copy-number alterations. Fusion junctions of the rearrangement resided within non-repeat sequences and were accompanied by short-templated insertions. CONCLUSIONS: Our results indicate that maternally derived copy-number gains in the GNAS region mediated by nonhomologous end-joining and/or by break-induced replication can underlie autosomal dominant PHP-1b. These rearrangements likely affect methylation of exon A/B-DMR by disconnecting or disrupting its cis-acting regulator(s). This study provides a novel example of human disorders resulting from functional disturbance in the cis-regulatory machinery of DNA methylation. PMID- 27253670 TI - Is H Atom Abstraction Important in the Reaction of Cl with 1-Alkenes? AB - The relative yields of products of the reaction of Cl atoms with 1-alkenes (C4 C9) were determined to see whether H atom abstraction is an important channel and if it is to identify the preferred position of abstraction. The presence of all the possible positional isomers of long chain alkenones and alkenols among the products, along with chloroketones and chloroalcohols, confirms the occurrence of H atom abstraction. A consistent pattern of distribution of abstraction products is observed with oxidation at C4 (next to allyl) being the lowest and that at CH2 groups away from the double bond being the highest. This contradicts with the higher stability of allyl (C3) radical. For a better understanding of the relative reactivity, ab initio calculations at MP2/6-311+G (d,p) level of theory are carried out in the case of 1-heptene. The total rate coefficient, calculated using conventional transition state theory, was found to be in good agreement with the experimental value at room temperature. The preferred position of Cl atom addition is predicted to be the terminal carbon atom, which matches with the experimental observation, whereas the rate coefficients calculated for individual channels of H atom abstraction do not explain the observed pattern of products. The distribution of abstraction products except at C4 is found to be better explained by reported structure activity relationship, developed from experimental rate coefficient data. This implies the reactions to be kinetically dictated and emphasizes the importance of secondary reactions. PMID- 27253672 TI - Rhodium-Catalyzed ortho-Amidations in the Preparation of Thiadiazine 1-Oxides. AB - Rhodium-catalyzed ortho-amidations of sulfoximines lead to key intermediates for the preparation of thiadiazine 1-oxides. Following a straightforward protocol, a variety of synthetically valuable compounds can be obtained, thus circumventing common multistep approaches towards potentially bioactive products. PMID- 27253668 TI - A Longitudinal Follow-up of Autoimmune Polyendocrine Syndrome Type 1. AB - CONTEXT: Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disease defined by the presence of two of the three major components: hypoparathyroidism, primary adrenocortical insufficiency, and chronic mucocutaneous candidiasis (CMC). Information on longitudinal follow-up of APS1 is sparse. OBJECTIVE: To describe the phenotypes of APS1 and correlate the clinical features with autoantibody profiles and autoimmune regulator (AIRE) mutations during extended follow-up (1996-2016). PATIENTS: All known Norwegian patients with APS1. RESULTS: Fifty-two patients from 34 families were identified. The majority presented with one of the major disease components during childhood. Enamel hypoplasia, hypoparathyroidism, and CMC were the most frequent components. With age, most patients presented three to five disease manifestations, although some had milder phenotypes diagnosed in adulthood. Fifteen of the patients died during follow-up (median age at death, 34 years) or were deceased siblings with a high probability of undisclosed APS1. All except three had interferon-omega) autoantibodies, and all had organ-specific autoantibodies. The most common AIRE mutation was c.967_979del13, found in homozygosity in 15 patients. A mild phenotype was associated with the splice mutation c.879+1G>A. Primary adrenocortical insufficiency and type 1 diabetes were associated with protective human leucocyte antigen genotypes. CONCLUSIONS: Multiple presumable autoimmune manifestations, in particular hypoparathyroidism, CMC, and enamel hypoplasia, should prompt further diagnostic workup using autoantibody analyses (eg, interferon-omega) and AIRE sequencing to reveal APS1, even in adults. Treatment is complicated, and mortality is high. Structured follow-up should be performed in a specialized center. PMID- 27253669 TI - Weight Loss and Lowering Androgens Predict Improvements in Health-Related Quality of Life in Women With PCOS. AB - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with reduced health related quality of life (HRQOL) and increased prevalence of depressive and anxiety disorders. The impact of PCOS-specific treatments on these co-morbidities is unclear. OBJECTIVE: To assess the impact of weight loss and decreasing hyperandrogenism on HRQOL and mood and anxiety disorders in women with PCOS. DESIGN/SETTING/PARTICIPANTS: A secondary analysis of a randomized controlled trial (OWL-PCOS) of preconception treatment conducted at two academic centers in women (age, 18-40 years; body mass index, 27-42 kg/m(2)) with PCOS defined by Rotterdam criteria. INTERVENTION: Continuous oral contraceptive pill (OCP) or intensive lifestyle intervention or the combination (Combined) for 16 weeks. MAIN OUTCOME MEASURE(S): Changes in HRQOL assessed by PCOSQ and SF-36 and prevalence of depression and anxiety disorder assessed by PRIME-MD PHQ. RESULTS: The lowest scores were noted on the general health domain of the SF-36 and the weight and infertility domains on the PCOSQ. All three interventions resulted in significant improvement in the general health score on the SF-36. Both the OCP and Combined groups showed improvements in all domains of the PCOSQ (P < .01) compared to baseline scores. The Combined group had significant improvements in the weight, body hair, and infertility domains compared to a single treatment group (P < .05). In a linear regression model, change in weight correlated with improvements in the weight domain (P < .001) and physical well-being (P < .02), change in T correlated with improvements in the hair domain (P < .001), and change in both weight and T correlated with the infertility (P < .001) and menstrual domains (P < .05). CONCLUSIONS: Both weight loss and OCP use result in significant improvements in several physical and mental domains related to quality of life, depressive symptoms, and anxiety disorders, and combined therapies offer further benefits in overweight/obese women with PCOS. PMID- 27253673 TI - Cs2CO3 as a source of carbonyl and ethereal oxygen in a Cu-catalysed cascade synthesis of benzofuran [3,2-c] quinolin-6[5-H]ones. AB - The simultaneous construction of C-C, C-O, and C-N bonds utilizing Cs2CO3 as a source of both carbonyl (CO) and ethereal oxygen and a cascade synthesis of benzofuro[3,2-c]quinolin-6(5H)-one have been achieved using a combination of Cu(OAc)2 and Ag2CO3. A plausible mechanism has been proposed for this unprecedented transformation. PMID- 27253676 TI - Does the circadian clock drift when pilots fly multiple transpacific flights with 1- to 2-day layovers? AB - On trips with multiple transmeridian flights, pilots experience successive non-24 h day/night cycles with circadian and sleep disruption. One study across a 9-day sequence of transpacific flights (no in-flight sleep, 1-day layovers between flights) reported an average period in the core body temperature rhythm of 24.6 h (circadian drift). Consequently, pilots were sometimes flying through the circadian performance nadir and had to readapt to home base time at the end of the trip. The present study examined circadian drift in trip patterns with longer flights and in-flight sleep. Thirty-nine B747-400 pilots (19 captains, 20 first officers, mean age = 55.5 years) were monitored on 9- to 13-day trips with multiple return flights between East Coast USA and Japan (in 4-pilot crews) and between Japan and Hawaii (in 3-pilot crews), with 1-day layovers between each flight. Measures included total in-flight sleep (actigraphy, log books) and top of descent (TOD) measures of sleepiness (Karolinska Sleepiness Scale), fatigue (Samn-Perelli Crew Status Check) and psychomotor vigilance task (PVT) performance. Circadian rhythms of individual pilots were not monitored. To detect circadian drift, mixed-model analysis of variance examined whether for a given flight, total in-flight sleep and TOD measures varied according to when the flight occurred in the trip sequence. In addition, sleep propensity curves for pre-trip and post-trip days were examined (Chi-square periodogram analyses). Limited data suggest that total in-flight sleep of relief crew at landing may have decreased across successive East Coast USA-Japan (flights 1, 3, 5 or 7; median arrival 03:45 Eastern Daylight Time (EDT)). However, PVT response speed at TOD was faster on East Coast USA-Japan flights later in the trip. On these flights, circadian drift would result in flights later in the trip landing closer to the evening wake maintenance zone, when sleep is difficult and PVT response speeds are fastest. On Japan-East Coast USA flights (flights 2, 4, 6 or 8; median arrival time 14:52 EDT), PVT response speeds were slower on flight 8 than on flight 2. Circadian drift would move these arrivals progressively earlier in the SCN pacemaker cycle, where PVT response speeds are slower. Across the five post trip days, 12 pilots (Group A) immediately resumed their pre-trip sleep pattern of a single nocturnal sleep episode; 9 pilots (Group B) had a daytime nap on most days that moved progressively earlier until it merged with nocturnal sleep and 17 pilots (Group C) had nocturnal sleep and intermittent naps. Chi-square periodogram analyses of the sleep propensity curves for each group across baseline and post-trip days suggest full adaptation to EDT from post-trip day 1 (dominant period = 24 h). However, in Groups B and C, the patterns of split sleep post-trip compared to pre-trip suggest that this may be misleading. We conclude that the trends in total in-flight sleep and significant changes in PVT performance speed at TOD provide preliminary evidence for circadian drift, as do persistent patterns of split sleep post-trip. However, new measures to track circadian rhythms in individual pilots are needed to confirm these findings. PMID- 27253677 TI - Formation of supramolecular assemblies and liquid crystals by purine nucleobases and cyanuric acid in water: implications for the possible origins of RNA. AB - The free nucleobases and mononucleotides of RNA do not form Watson-Crick base pairs in water, a fact that presents several challenges for the prebiotic synthesis of RNA. 2,6-Diaminopurine and adenosine-5'-monophosphate (AMP) are shown to form supramolecular assemblies with cyanuric acid in water. These assemblies and their propensity to form liquid crystals suggest a possible means by which non-covalent structures might have originally selected the shape of the Watson-Crick base pairs. PMID- 27253678 TI - N-Acetyl glycals are tight-binding and environmentally insensitive inhibitors of hexosaminidases. AB - Mono-, di- and trisaccharide derivatives of 1,2-unsaturated N-acetyl-d-glucal have been synthesized and shown to function as tight-binding inhibitors/slow substrates of representative hexosaminidases. Turnover is slow and not observed in the thioamide analogue, allowing determination of the 3-dimensional structure of the complex. Inhibition is insensitive to pH and to mutation of key catalytic residues, consistent with the uncharged character of the inhibitor. These properties could render this inhibitor class less prone to development of resistance. PMID- 27253679 TI - Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer's Agents: Synthesis and Biological Evaluation. AB - A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 +/- 0.01 MUM) for AChE and (1.84 +/- 0.03 MUM) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced Abeta1-42 aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing Abeta1-42-induced toxicity by attenuating abnormal levels of Abeta1-42, p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects. PMID- 27253680 TI - The role of visual representations in college students' understanding of mathematical notation. AB - Developing understanding of fractions involves connections between nonsymbolic visual representations and symbolic representations. Initially, teachers introduce fraction concepts with visual representations before moving to symbolic representations. Once the focus is shifted to symbolic representations, the connections between visual representations and symbolic notation are considered to be less useful, and students are rarely asked to connect symbolic notation back to visual representations. In 2 experiments, we ask whether visual representations affect understanding of symbolic notation for adults who understand symbolic notation. In a conceptual fraction comparison task (e.g., Which is larger, 5 / a or 8 / a?), participants were given comparisons paired with accurate, helpful visual representations, misleading visual representations, or no visual representations. The results show that even college students perform significantly better when accurate visuals are provided over misleading or no visuals. Further, eye-tracking data suggest that these visual representations may affect performance even when only briefly looked at. Implications for theories of fraction understanding and education are discussed. PMID- 27253684 TI - Web focus. AB - This regular feature highlights websites with information on clinical subjects. PMID- 27253690 TI - Pharmacokinetic and pharmacodynamic evaluation of oxycodone and naltrexone for the treatment of chronic lower back pain. AB - INTRODUCTION: Chronic low back pain (CLBP) is a common and difficult illness to manage. Some individuals with CLBP have pain processing disorders and are also at risk for opioid abuse, misuse; addiction and diversion. Guidelines have been published to guide management; neuromodulation, exercise, mindfulness-based stress reduction and cognitive behavior therapies among other non-pharmacological reduce the pain of CLBP with minimal toxicity. Pharmacological management includes acetaminophen, NSAIDs and antidepressants, mainly duloxetine. Abuse deterrent opioids have been developed which have been shown to reduce pain and opioid abuse risk. ALO-02 is a tamper-resistant sustained release opioid consisting of extended release oxycodone and sequestered naltrexone. Pivotal studies of ALO-02 have centered on patients with CLBP. AREAS COVERED: This manuscript will review CLBP, the pivotal analgesic and clinical abuse potential studies of ALO-02. The opinion will cover whether opioids should be used for CLBP, when they should be used and opioid choices. EXPERT OPINION: ALO-02 is one of several opioids which can be considered in the management of CLBP. The outcome to a trial of opioids should be function rather than analgesia. Most analgesic trials for CLBP have had analgesia as the primary outcome and function has not been vigorously studied as an outcome. Opioids should be considered as a trial only when other non-opioid analgesics have failed to improve analgesia and function. Universal precautions should be routinely part of phase III analgesic trial particularly for chronic non-malignant pain. PMID- 27253691 TI - Atomic force microscopy observation and characterization of single virions and virus-like particles by nano-indentation. AB - Structure and function of viruses are intimately related, and one of the goals in virology is to elucidate the mechanisms behind this relation. A variety of research endeavours is focused on studying these mechanisms and a relatively new technique in this field is Atomic Force Microscopy (AFM). Using AFM virions and virus-like particles can be imaged and manipulated at the single particle level. Here we review recent AFM nano-indentations studies unveiling for instance the mechanics of capsid-genome interactions, morphological changes that drive viral maturation, capsid stabilizing factors and viral uncoating. We show that in an increasing amount of literature a clear link between mechanics and infectivity is observed, which not only provides us with new fundamental insights into virology, but also provides ways to improve virus-like particles for applications in nanomedicine and nanotechnology. PMID- 27253692 TI - Developing immunotherapeutic strategies to target brain tumors. AB - INTRODUCTION: Recent years have seen rapid growth in cancer treatments that enhance the anti-tumor activities of the immune system. Collectively known as immunotherapy, modulation of the immune system has shown success treating some hematological malignancies, but has yet to be successfully applied to the treatment of patients with brain tumors. AREAS COVERED: This review highlights mechanistic insights from murine studies and compiled recent clinical trial data, focusing on the most aggressive brain tumor, glioblastoma (GBM). The field has recently accumulated a critical mass of data, and we discuss past treatment failures in the context of newly developed approaches now entering clinical trials. This article provides an overview of the immunotherapeutic armamentarium currently in development for the treatment of patients with GBM, who are in dire need of safe and effective therapies. Expert commentary: Themes that emerge include the importance of mitigating the effects of an immunosuppressive tumor microenvironment and the potential for innate immune cell activation to enhance cytotoxic anti-tumor activity. Consideration of these studies as a collective may inform the design of new immunotherapies, as well as the immune monitoring protocols for patients participating in clinical trials. PMID- 27253693 TI - Health and Climate-Relevant Pollutant Concentrations from a Carbon-Finance Approved Cookstove Intervention in Rural India. AB - Efforts to introduce more efficient stoves increasingly leverage carbon-finance to scale up dissemination of interventions. We conducted a randomized intervention study to evaluate a Clean Development Mechanism approved stove replacement impact on fuelwood usage, and climate and health-relevant air pollutants. We randomly assigned 187 households to either receive the intervention or to continue using traditional stoves. Measurements of fine particulate matter (PM2.5) and absorbance were conducted in cooking areas, village center and at upwind background site. There were minor and overlapping seasonal differences (post- minus preintervention change) between control and intervention groups for median (95% CI) fuel use (-0.60 (-1.02, -0.22) vs -0.52 ( 1.07, 0.00) kg day(-1)), and 24 h absorbance (35 (18, 60) vs 36 (22, 50) * 10(-6) m(-1)); for 24 h PM2.5, there was a higher (139 (61,229) vs 73(-6, 156) MUg m( 3))) increase in control compared to intervention homes between the two seasons. Forty percent of the intervention homes continued using traditional stoves. For intervention homes, absorbance-to-mass ratios suggest a higher proportion of black carbon in PM2.5 emitted from intervention compared with traditional stoves. Absent of field-based evaluation, stove interventions may be pursued that fail to realize expected carbon reductions or anticipated health and climate cobenefits. PMID- 27253694 TI - Cancer treatment and survivorship statistics, 2016. AB - The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. (c) 2016 American Cancer Society. PMID- 27253696 TI - Ionotropic Receptors Identified within the Tentacle of the Freshwater Snail Biomphalaria glabrata, an Intermediate Host of Schistosoma mansoni. AB - Biomphalaria glabrata (B. glabrata) is an air-breathing aquatic mollusc found in freshwater habitats across the Western Hemisphere. It is most well-known for its recognized capacity to act as a major intermediate host for Schistosoma mansoni, the human blood fluke parasite. Ionotropic receptors (IRs), a variant family of the ionotropic glutamate receptors (iGluR), have an evolutionary ancient function in detecting odors to initiate chemosensory signaling. In this study, we applied an array of methods towards the goal of identifying IR-like family members in B. glabrata, ultimately revealing two types, the iGluR and IR. Sequence alignment showed that three ligand-binding residues are conserved in most Biomphalaria iGluR sequences, while the IRs did exhibit a variable pattern, lacking some or all known glutamate-interactingresidues, supporting their distinct classification from the iGluRs. We show that B. glabrata contains 7 putative IRs, some of which are expressed within its chemosensory organs. To further investigate a role for the more ancient IR25a type in chemoreception, we tested its spatial distribution pattern within the snail cephalic tentacle by in situ hybridization. The presence of IR25a within presumptive sensory neurons supports a role for this receptor in olfactory processing, contributing to our understanding of the molecular pathways that are involved in Biomphalaria olfactory processing. PMID- 27253695 TI - Depletion of Histone Demethylase Jarid1A Resulting in Histone Hyperacetylation and Radiation Sensitivity Does Not Affect DNA Double-Strand Break Repair. AB - Histone demethylases have recently gained interest as potential targets in cancer treatment and several histone demethylases have been implicated in the DNA damage response. We investigated the effects of siRNA-mediated depletion of histone demethylase Jarid1A (KDM5A, RBP2), which demethylates transcription activating tri- and dimethylated lysine 4 at histone H3 (H3K4me3/me2), on growth characteristics and cellular response to radiation in several cancer cell lines. In unirradiated cells Jarid1A depletion lead to histone hyperacetylation while not affecting cell growth. In irradiated cells, depletion of Jarid1A significantly increased cellular radiosensitivity. Unexpectedly, the hyperacetylation phenotype did not lead to disturbed accumulation of DNA damage response and repair factors 53BP1, BRCA1, or Rad51 at damage sites, nor did it influence resolution of radiation-induced foci or rejoining of reporter constructs. We conclude that the radiation sensitivity observed following depletion of Jarid1A is not caused by a deficiency in repair of DNA double-strand breaks. PMID- 27253698 TI - Major Depression in Canada: What Has Changed over the Past 10 Years? AB - OBJECTIVE: Major depressive episodes (MDE) make an important contribution to disease burden in Canada. The epidemiology of MDE in the national population has been examined in 2 mental health surveys, one conducted in 2002 and the other in 2012. Our objective was to compare selected variables from the 2 surveys to determine whether changes have occurred in the prevalence, treatment, and impact of MDE. METHOD: The World Health Organization World Mental Health Composite International Diagnostic Interview was used in both surveys and the MDE module (which was not modified) was scored using the same algorithm. Some variables assessing impact and management of MDE were also identical in the 2 surveys. The analysis was based on frequency estimates and associated 95% confidence intervals. RESULTS: The annual prevalence of MDE was 4.7% (95% CI 4.3% to 5.1%) in 2012, nearly identical to 4.8% (95% CI 4.5% to 5.1%) in 2002. Receipt of potentially adequate treatment (defined as taking an antidepressant or 6 or more visits to a health professional for mental health reasons) increased from 41.3% in 2002 to 52.2% in 2012, mostly due to an increase in respondents reporting 6 or more visits. Use of second generation antipsychotics also increased. There was no evidence of diminishing prevalence or impact (as assessed by symptoms of distress). CONCLUSIONS: There appears to have been an increase in receipt of treatment for people with MDE and a changing pattern of management. However, it was not possible to confirm that the impact of MDE is diminishing as a result. PMID- 27253697 TI - A Review of 20 Years of Research on Overdiagnosis and Underdiagnosis in the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project. AB - The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project represents an integration of research methodology into a community-based outpatient practice affiliated with an academic medical centre. The MIDAS project is the largest clinical epidemiological study using semi-structured interviews to assess a wide range of psychiatric disorders in a general clinical outpatient practice. In an early report from the MIDAS project, we found that across diagnostic categories clinicians using unstandardized, unstructured clinical interviews underrecognized diagnostic comorbidity, compared with the results of semi-structured interviews. Moreover, we found that the patients often wanted treatment for symptoms of disorders that were diagnosed as comorbid, rather than principal, conditions. This highlighted the importance, from the patient's perspective, of conducting thorough diagnostic interviews to diagnose disorders that are not related to the patient's chief complaint because patients often desire treatment for these additional diagnoses. While several of the initial papers from the MIDAS project identified problems with the detection of comorbid disorders in clinical practice, regarding the diagnosis of bipolar disorder we observed the emergence of an opposite phenomenon-clinician overdiagnosis. The results from the MIDAS project, along with other studies of diagnosis in routine clinical practice, have brought to the forefront the problem with diagnosis in routine clinical practice. An important question is what do these findings suggest about the community standard of care in making psychiatric diagnoses, and whether and how the standard of care should be changed? The implications are discussed. PMID- 27253699 TI - Career Interests of Canadian Psychiatry Residents: What Makes Residents Choose a Research Career? AB - OBJECTIVES: Training future clinician-researchers remains a challenge faced by Canadian psychiatry departments. Our objectives were to determine the prevalence of residents interested in pursuing research and other career options as part of their practice, and to identify the factors associated with interest in research. METHOD: Data from a national online survey of 207 Canadian psychiatry residents from a total of 853 (24.3% response rate) were examined. The main outcome was interest in research as part of residents' future psychiatrist practice. Bivariate and multivariate analyses were performed to identify demographic and vocational variables associated with research interest. RESULTS: Interest in research decreases by 76% between the first and fifth year of psychiatry residency (OR 0.76 per year, 95% CI 0.60 to 0.97). Training in a department with a residency research track did not correlate with increased research interest (chi2 = 0.007, df = 1, P = 0.93). CONCLUSIONS: Exposing and engaging psychiatry residents in research as early as possible in residency training appears key to promoting future research interest. Psychiatry residency programs and research tracks could consider emphasizing research training initiatives and protected research time early in residency. PMID- 27253700 TI - Investigating Possible Reciprocal Relations Between Depressive and Problem Gambling Symptoms in Emerging Adults. AB - OBJECTIVE: Previous cross-sectional research has shown that depression and problem gambling co-occur. Longitudinal research, however, allows for a better determination of directionality, as behavioural changes in gambling involvement can be more reliably studied over time. Our study assesses symptoms of depression and problem gambling across 4 waves and addresses whether their relation is directional (with one reliably preceding the other), bidirectional, or pathoplastic. METHOD: As part of the Manitoba Longitudinal Study of Young Adults, prospective data were collected on Canadian young adults' (Wave 1: n = 679, 51.8% female, aged 18 to 20 years) depressive symptoms, involvement in gambling, and risky gambling behaviour. Recruitment and the first cycle of data collection (Wave 1) took place in fall 2007. Three additional waves of data collection then occurred in 12- to 18-month intervals: fall 2008, spring 2010, and spring 2011. The Problem Gambling Severity Index and the Composite International Diagnostic Interview-Short Form were administered through telephone interview at each wave. RESULTS: Bivariate growth curves showed that depressive and problem gambling symptoms were positively correlated at Wave 1, Wave 2, and Wave 4. Neither disorder was found to be a risk factor for the other, and depression and problem gambling were not pathoplastically related (that is, increases in one did not result in increases in the other over time, and vice versa). CONCLUSIONS: While depression and problem gambling are related, their co-occurrence may be better explained not by depressive- or gambling-related risk, but by the presence of a common underlying factor (such as substance abuse). PMID- 27253701 TI - A Longitudinal Study of the Temporal Relation Between Problem Gambling and Mental and Substance Use Disorders Among Young Adults. AB - OBJECTIVE: Relatively little is known about the temporal relation between at-risk gambling or problem gambling (PG) and mental and substance use disorders (SUDs) in young adulthood. Our study aimed to examine whether past-year, at-risk, or PG is associated with incident mental disorders and SUDs (that is, depression, generalized anxiety disorder, obsessive-compulsive disorder [OCD], or alcohol dependence) and illegal drug use, and whether past-year mental disorders and SUDs and illegal drug use is associated with incident at-risk or PG. METHOD: Data for this longitudinal study were drawn from the Manitoba Longitudinal Study of Young Adults (MLSYA). Respondents aged 18 to 20 years in 2007 were followed prospectively for 5 years. RESULTS: In cross-sectional analyses, at-risk or PG was associated with increased odds of depression, OCD, alcohol dependence, and illegal drug use. In longitudinal analysis at-risk or PG at cycle 1 was associated with incident major depressive disorder, alcohol dependence, and illegal drug use in the follow-up period. Only illegal drug use at cycle 1 was associated with incident at-risk or PG during follow-up. CONCLUSIONS: At-risk or PG was associated with more new onset mental disorders and SUDs (depression, alcohol dependence, and illegal drug use), compared with the reverse (illegal drug use was the only association with new onset at-risk or PG). Preventing at risk or PG from developing early in adulthood may correspond with decreases in new onset mental disorders and SUDs later in adulthood. PMID- 27253702 TI - Forty-Five Years of Civil Litigation Against Canadian Psychiatrists: An Empirical Pilot Study. AB - OBJECTIVES: To extract the themes pertaining to prudent psychiatric practice from written court judgments in Canada. METHODS: We searched the medical and legal literature for cases involving civil litigation against Canadian psychiatrist and reviewed all available written judgments. We completed a thematic analysis of the civil actions against psychiatrists as conveyed by those written court judgments. We classified the cases according to the disposal status and the essential lessons from the decisions on standard of care and practice by Canadian psychiatrists. RESULTS: Forty such cases were identified as involving psychiatrists over a 45-year period. A subgroup included those dealing with limitation periods and disclosure applications. Thirty of the 40 cases (75%) were decided in favour of the defendant psychiatrists, including 2 dismissed for running over the limitation period. The cases that actually went to trial suggest that documentation and obtaining second opinions are protective against claims of negligence. Inpatient cases resulting in successful litigation against psychiatrists involved fatal outcomes, but not all fatal outcomes led to successful litigation. CONCLUSIONS: The key lessons from these cases are the importance and relevance of regular best clinical practices, such as documentation, obtaining second opinions, following guidelines, and balancing competencies in the expert and manager or advocate roles. Incorporating these practices should allay concerns about litigation against psychiatrists. PMID- 27253704 TI - Acadian Mental Health: A Review of Published Literature. PMID- 27253703 TI - Mental Health Service Use Among Children and Youth in Ontario: Population-Based Trends Over Time. AB - OBJECTIVE: Little is known about mental health service use among Canadian children and youth. Our objective was to examine temporal trends in mental health service use across different sectors of the health care system among children and youth living in Ontario. METHODS: We conducted a population-based, repeated annual cross-sectional study of mental health service use, including mental health- and addictions-related emergency department (ED) visits, psychiatric hospitalizations, and mental health-related outpatient physician visits using linked health administrative databases. Subjects included Ontario residents between 10 and 24 years of age. We tested temporal trends between 2006 and 2011 using linear regression models. RESULTS: Between 2006 and 2011, the relative increase in rates of mental health-related ED visits and hospitalizations were 32.5% and 53.7%, respectively. The absolute increase in anxiety disorders, the most common reason for ED visits, was 2.2 per 1000 population (P < 0.001) while mood and affective disorders, the most common reason for hospitalizations, showed an increase of 0.6 per 1000 population (P < 0.01). The overall relative increase in rates of outpatient visits was 15.8%, with the largest absolute increase found among family physician visits (28.7 per 1000 population, P = 0.01). CONCLUSIONS: Mental health care use for children and youth is increasing over time in all sectors, but appears to be increasing at a greater rate in the acute care sector. Further research is required to understand whether the observed differences reflect difficulty with access to outpatient care. PMID- 27253706 TI - Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound. AB - In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x107 CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 MUg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10 soaked foam dressing (containing 20 MUg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models. PMID- 27253707 TI - Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo. AB - Streptococcus (S.) pneumoniae strains vary considerably in their ability to cause invasive disease in humans, which is at least in part determined by the capsular serotype. Platelets have been implicated as sentinel cells in the circulation for host defence. One of their utensils for this function is the expression of Toll like receptors (TLRs). We here aimed to investigate platelet response to S. pneumoniae and a role for TLRs herein. Platelets were stimulated using four serotypes of S. pneumonia including an unencapsulated mutant strain. In vitro aggregation and flow cytometry assays were performed using blood of healthy volunteers, or blood of TLR knock out and WT mice. For in vivo pneumonia experiments, platelet specific Myd88 knockout (Plt-Myd88-/-) mice were used. We found that platelet aggregation was induced by unencapsulated S. pneumoniae only. Whole blood incubation with all S. pneumoniae serotypes tested resulted in platelet degranulation and platelet-leukocyte complex formation. Platelet activation was TLR independent, as responses were not inhibited by TLR blocking antibodies, not induced by TLR agonists and were equally induced in wild-type and Tlr2-/-, Tlr4-/-, Tlr2/4-/-, Tlr9-/- and Myd88-/- blood. Plt-Myd88-/- and control mice displayed no differences in bacterial clearance or immune response to pneumonia by unencapsulated S. pneumoniae. In conclusion, S. pneumoniae activates platelets through a TLR-independent mechanism that is impeded by the bacterial capsule. Additionally, platelet MyD88-dependent TLR signalling is not involved in host defence to unencapsulated S. pneumoniae in vivo. PMID- 27253708 TI - In Vivo MRI Measurement of Spinal Cord Displacement in the Thoracolumbar Region of Asymptomatic Subjects with Unilateral and Sham Straight Leg Raise Tests. AB - BACKGROUND: Normal displacement of the conus medullaris with unilateral and bilateral SLR has been quantified and the "principle of linear dependence" has been described. PURPOSE: Explore whether previously recorded movements of conus medullaris with SLRs are i) primarily due to transmission of tensile forces transmitted through the neural tissues during SLR or ii) the result of reciprocal movements between vertebrae and nerves. STUDY DESIGN: Controlled radiologic study. METHODS: Ten asymptomatic volunteers were scanned with a 1.5T magnetic resonance (MR) scanner using T2 weighted spc 3D scanning sequences and a device that permits greater ranges of SLR. Displacement of the conus medullaris during the unilateral and sham SLR was quantified reliably with a randomized procedure. Conus displacement in response to unilateral and sham SLRs was quantified and the results compared. RESULTS: The conus displaced caudally in the spinal canal by 3.54+/-0.87 mm (mean+/-SD) with unilateral (p<=.001) and proximally by 0.32+/-1.6 mm with sham SLR (p<=.542). Pearson correlations were higher than 0.99 for both intra- and inter-observer reliability and the observed power was 1 for unilateral SLRs and 0.054 and 0.149 for left and right sham SLR respectively. CONCLUSIONS: Four relevant points emerge from the presented data: i) reciprocal movements between the spinal cord and the surrounding vertebrae are likely to occur during SLR in asymptomatic subjects, ii) conus medullaris displacement in the vertebral canal with SLR is primarily due to transmission of tensile forces through the neural tissues, iii) when tensile forces are transmitted through the neural system as in the clinical SLR, the magnitude of conus medullaris displacement prevails over the amount of bone adjustment. PMID- 27253710 TI - Population targeting amid complex mental health programming: Are California's Full Service Partnerships reaching underserved children? AB - California's Mental Health Services Act (MHSA) created Full Service Partnership programs (FSPs) targeting socially and economically vulnerable children with mental illness who are underserved by counties' public mental health treatment system. To determine whether FSPs reach a distinctive group of children, this study compares indicators of FSP-targeted underservice for FSP entrants (n = 15,598) versus everyone treated in the counties' public mental health systems (n = 282,178) and for FSP entrants versus entrants in the most intensive Medicaid delivered program in California, Therapeutic Behavioral Services (TBS, n = 11,993). Results identify that, despite first encountering mental health services systems at earlier ages, FSP clients had fewer months of treatment and were less likely to have been treated in the prior 6 months, except for crisis care, as compared to all other children served, after considering clinical severity and indicators of service need. FSP entrants also had more substance abuse and trauma related problems. Although less seriously ill than TBS served children, FSP served children were significantly underserved. The results indicate that, amid overlapping policies and programs, carving out and reaching a distinctly underserved population can be achieved in practice, and that specialized programs, such as the FSP program, which target underserved children, have the potential to augment a system's ability to reach the underserved. (PsycINFO Database Record PMID- 27253709 TI - A Complex Structural Variation on Chromosome 27 Leads to the Ectopic Expression of HOXB8 and the Muffs and Beard Phenotype in Chickens. AB - Muffs and beard (Mb) is a phenotype in chickens where groups of elongated feathers gather from both sides of the face (muffs) and below the beak (beard). It is an autosomal, incomplete dominant phenotype encoded by the Muffs and beard (Mb) locus. Here we use genome-wide association (GWA) analysis, linkage analysis, Identity-by-Descent (IBD) mapping, array-CGH, genome re-sequencing and expression analysis to show that the Mb allele causing the Mb phenotype is a derived allele where a complex structural variation (SV) on GGA27 leads to an altered expression of the gene HOXB8. This Mb allele was shown to be completely associated with the Mb phenotype in nine other independent Mb chicken breeds. The Mb allele differs from the wild-type mb allele by three duplications, one in tandem and two that are translocated to that of the tandem repeat around 1.70 Mb on GGA27. The duplications contain total seven annotated genes and their expression was tested during distinct stages of Mb morphogenesis. A continuous high ectopic expression of HOXB8 was found in the facial skin of Mb chickens, strongly suggesting that HOXB8 directs this regional feather-development. In conclusion, our results provide an interesting example of how genomic structural rearrangements alter the regulation of genes leading to novel phenotypes. Further, it again illustrates the value of utilizing derived phenotypes in domestic animals to dissect the genetic basis of developmental traits, herein providing novel insights into the likely role of HOXB8 in feather development and differentiation. PMID- 27253711 TI - The moderating role of cultural affiliation in the link between emotional closeness to grandparents and adolescent adjustment difficulties and prosocial behavior. AB - A growing body of research has shown the positive contribution of grandparents to adolescents' well-being. However, studies often overlook the cultural context in which this relationship is embedded. The current study examined whether emotional closeness to the grandparent identified by the adolescents as their closest grandparent varied among Arab and Jewish adolescents and whether cultural affiliation serves as a moderator in the association between emotional closeness to grandparents and adolescent adjustment difficulties and prosocial behaviors. The study was based on a sample of 2,751 Jewish and Arab secondary school students (aged 12-18) from Israel who completed a structured questionnaire. Among the whole sample, greater emotional closeness to the closest grandparent was associated with reduced emotional symptoms, reduced hyperactivity, and increased prosocial behaviors. While there were lower levels of emotional closeness to the closest grandparents among Arab adolescents, emotional closeness to grandparents was found to be more strongly associated with reduced emotional symptoms and increased prosocial behavior among Arab adolescents than among Jewish adolescents. These findings emphasize the importance of considering culture when examining intergenerational relationships in the family and their contribution to grandchildren's well-being. (PsycINFO Database Record PMID- 27253712 TI - A Mechanistic Model of Intermittent Gastric Emptying and Glucose-Insulin Dynamics following a Meal Containing Milk Components. AB - To support decision-making around diet selection choices to manage glycemia following a meal, a novel mechanistic model of intermittent gastric emptying and plasma glucose-insulin dynamics was developed. Model development was guided by postprandial timecourses of plasma glucose, insulin and the gastric emptying marker acetaminophen in infant calves fed meals of 2 or 4 L milk replacer. Assigning a fast, slow or zero first-order gastric emptying rate to each interval between plasma samples fit acetaminophen curves with prediction errors equal to 9% of the mean observed acetaminophen concentration. Those gastric emptying parameters were applied to glucose appearance in conjunction with minimal models of glucose disposal and insulin dynamics to describe postprandial glycemia and insulinemia. The final model contains 20 parameters, 8 of which can be obtained by direct measurement and 12 by fitting to observations. The minimal model of intestinal glucose delivery contains 2 gastric emptying parameters and a third parameter describing the time lag between emptying and appearance of glucose in plasma. Sensitivity analysis of the aggregate model revealed that gastric emptying rate influences area under the plasma insulin curve but has little effect on area under the plasma glucose curve. This result indicates that pancreatic responsiveness is influenced by gastric emptying rate as a consequence of the quasi-exponential relationship between plasma glucose concentration and pancreatic insulin release. The fitted aggregate model was able to reproduce the multiple postprandial rises and falls in plasma glucose concentration observed in calves consuming a normal-sized meal containing milk components. PMID- 27253714 TI - ZNC opens a new chapter focussing on the emerging field of natural and natural like compounds. PMID- 27253713 TI - Enhanced Th2 cell differentiation and function in the absence of Nox2. AB - BACKGROUND: Patients with chronic granulomatous disease (CGD), whom inherit abnormal function of NADPH oxidase 2 (Nox2), suffer from hyperinflammatory responses in lung as well as bacterial and fungal infection. There have been studies to reveal the function of Nox2 in hyperinflammatory diseases, especially in asthma, but the exact role of Nox2 in asthma is still unclear and controversial. Therefore, we attempted to clarify the exact role of Nox2 in asthma, using various experimental asthma models. METHODS: Asthma phenotypes were analyzed in response to various allergen-induced experimental asthma using Nox2 deficient mice and recombinase gene-activating-1-deficient mice. To understand the underlying mechanisms of exaggerated Th2 effector functions, we investigated the degree of T-cell activation, levels of activation-induced cell death (AICD), and regulatory T (Treg)-cell differentiation in Nox2-deficient T cells. RESULTS: Asthma phenotypes were increased through enhanced Th2 differentiation and function in Nox2-null mice regardless of dose and route of various allergens. Nox2-deficient T cells also showed hyperactivation, reduced AICD, and diminished Treg-cell differentiation through increased AKT phosphorylation (T308/S473) and enhanced mitochondrial ROS production. CONCLUSION: Our findings indicate that Nox2 deficiency results in exaggerated experimental asthma, which is caused by enhanced Th2 effector function in a T-cell-intrinsic manner. PMID- 27253715 TI - An Evolved RNA Recognition Motif That Suppresses HIV-1 Tat/TAR-Dependent Transcription. AB - Potent and selective recognition and modulation of disease-relevant RNAs remain a daunting challenge. We previously examined the utility of the U1A N-terminal RNA recognition motif as a scaffold for tailoring new RNA hairpin recognition and showed that as few as one or two mutations can result in moderate affinity (low MUM dissociation constant) for the human immunodeficiency virus (HIV) trans activation response element (TAR) RNA, an RNA hairpin controlling transcription of the human immunodeficiency virus (HIV) genome. Here, we use yeast display and saturation mutagenesis of established RNA-binding regions in U1A to identify new synthetic proteins that potently and selectively bind TAR RNA. Our best candidate has truly altered, not simply broadened, RNA-binding selectivity; it binds TAR with subnanomolar affinity (apparent dissociation constant of ~0.5 nM) but does not appreciably bind the original U1A RNA target (U1hpII). It specifically recognizes the TAR RNA hairpin in the context of the HIV-1 5'-untranslated region, inhibits the interaction between TAR RNA and an HIV trans-activator of transcription (Tat)-derived peptide, and suppresses Tat/TAR-dependent transcription. Proteins described in this work are among the tightest TAR RNA binding reagents-small molecule, nucleic acid, or protein-reported to date and thus have potential utility as therapeutics and basic research tools. Moreover, our findings demonstrate how a naturally occurring RNA recognition motif can be dramatically resurfaced through mutation, leading to potent and selective recognition-and modulation-of disease-relevant RNA. PMID- 27253716 TI - Radiolead (210)Pb and (210)Po/(210)Pb activity ratios in calcium supplements and the assessment of their possible dose to consumers. AB - This paper presents the results of pioneer study of the most popular calcium supplements as a potential additional source of radiolead (210)Pb in human diet. The analyzed calcium pharmaceutics contained organic or inorganic calcium compounds; some came from natural sources as mussels' shells, fish extracts, or sedimentary rocks. The idea was to investigate the naturally occurring (210)Pb activity in different calcium supplements and calculate the annual effective radiation dose from radiolead (210)Pb decay in consumed calcium supplement. The results showed (210)Pb concentrations in natural origin calcium supplements (especially sedimentary rocks) were significantly higher. The highest (210)Pb activity concentrations were determined in mineral tablets made from dolomite - 2.97 +/- 0.18 mBq g(-1), while the lowest was observed in organic calcium compounds - both calcium lactate - 0.08 +/- 0.01 and 0.13 +/- 0.01 mBq g(-1). The highest annual radiation dose from (210)Pb taken with 1 tablet of calcium supplement per day was calculated for soluble calcium lactate sample - 1.19 +/- 0.03 uSv year(-1), while the highest annual radiation dose from (210)Pb taken daily with 1 g of pure Ca for dolomite - 5.57 +/- 0.34 uSv year(-1). PMID- 27253717 TI - Fiber loss in diabetic polyneuropathy. PMID- 27253718 TI - The Effect of Nitrogen Deposition on Plant Performance and Community Structure: Is It Life Stage Specific? AB - Nitrogen (N) deposition is a key global change factor that is increasing and affecting the structure and function of many ecosystems. To determine the influence of N deposition on specific systems, however, it is crucial to understand the temporal and spatial patterns of deposition as well as the response to that deposition. Response of the receiving plant communities may depend on the life stage-specific performance of individual species. We focus on the California oak savanna because N deposition to this system is complex characterized by hotspots on the landscape and seasonal pulses. In a greenhouse experiment, we investigated the relative influence of N deposition on plant performance during early growth, peak biomass, and senescent life stages across different soil types, light, and community compositions. To represent the community we used three grass species-a native, naturalized exotic, and invasive exotic. At early growth and peak biomass stages performance was measured as height, and shoot and root biomass, and at the senescent stage as seed production. Simulated N deposition 1) increased shoot biomass and height of the native and, even more so, the naturalized exotic during early growth, 2) positively affected root biomass in all species during peak biomass, and 3) had no influence on seed production at the senescent stage. Alone, N deposition was not a strong driver of plant performance; however, small differences in performance among species in response to N deposition could affect community composition in future years. In particular, if there is a pulse of N deposition during the early growth stage, the naturalized exotic may have a competitive advantage that could result in its spread. Including spatial and temporal heterogeneity in a complex, manipulative experiment provides a clearer picture of not only where N management efforts should be targeted on the landscape, but also when. PMID- 27253719 TI - Metal-Organic Coordination Networks: Prussian Blue and Its Synergy with Pt Nanoparticles to Enhance Oxygen Reduction Kinetics. AB - Oxygen reduction reaction (ORR) is the cornerstone in the electrochemical energy conversion devices such as fuel cells and metal-air batteries. It remains a great challenge to develop the ORR electrocatalysts with fast kinetics and high durability. Herein, we report the synthesis of a novel metal-organic coordination networks material, prussian blue crystalline nanograins mosaicked within amorphous membrane (PB CNG-M-AM). Such unique PB CNG-M-AM is designed to enhance the electrocatalysis of Pt toward the ORR by the electrostatic self-assembly. Thus, obtained Pt-PB/C catalysts form numerous Pt-PB-gas three-phase boundaries and present rather high intrinsic activity, four-electron selectivity and superior stability. Moreover, a completely new synergetic mechanism between PB and Pt is discovered, which delicately alters the ORR route and significantly enhances the ORR kinetics. This work provides not only a new strategy and mechanism for developing highly efficient ORR electrocatalysts, but also an alternative way to utilize metal-organic coordination networks materials. PMID- 27253720 TI - Confined Water in Amyloid-Competent Oligomers of the Prion Protein. AB - Conformational switching of the prion protein into the abnormal form involves the formation of (obligatory) molten-oligomers that mature into ordered amyloid fibrils. The role of water in directing the course of amyloid formation remains poorly understood. Here, we show that the mobility of the water molecules within the on-pathway oligomers is highly retarded. The water relaxation time within the oligomers was estimated to be ~1 ns which is about three orders of magnitude slower than the bulk water and resembles the characteristics of (trapped) nano confined water. We propose that the coalescence of these obligatory oligomers containing trapped water is entropically favored because of the release of ordered water molecules in the bulk milieu and results in the sequestration of favorable inter-chain amyloid contacts via nucleated conformational conversion. The dynamic role of water in protein aggregation will have much broader implications in a variety of protein misfolding diseases. PMID- 27253721 TI - Immune-mediated mechanisms of atherosclerosis and implications for the clinic. AB - INTRODUCTION: A large body of evidence supports the inflammatory hypothesis of atherosclerosis, and both innate and adaptive immune responses play important roles in all disease stages. Areas covered: Here, we review our understanding of the role of the immune response in atherosclerosis, focusing on the pathways currently amenable to therapeutic modulation. We also discuss the advantages or undesirable effects that may be foreseen from targeting the immune response in patients at high cardiovascular risk, suggesting new avenues for research. Expert commentary: There is an extraordinary opportunity to directly test the inflammatory hypothesis of atherosclerosis in the clinic using currently available therapeutics. However, a more balanced interpretation of the experimental and translational data is needed, which may help address and identify in more detail the appropriate settings where an immune pathway can be targeted with minimal risk. PMID- 27253722 TI - Study of the Vapor Phase Over Fusarium Fungi Cultured on Various Substrates. AB - The compositions of volatile organic compounds (VOCs) emitted by Fusarium fungi (F. langsethiae, F. sibiricum, F. poae, and F. sporotrichioides) grown on two nutritive substrates: potato sucrose agar (PSA) and autoclaved wheat kernels (WK) were investigated. The culturing of fungi and study of their VOC emissions were performed in chromatographic vials at room temperature (23 - 24 degrees C) and the VOCs were sampled by a solid-phase microextraction on a 85 MUm carboxen/polydimethylsiloxane fiber. GC/MS was performed using a 60-m HP-5 capillary column. Components of the VOC mixture were identified by electron impact mass spectra and chromatographic retention indices (RIs). The most abundant components of the VOC mixture emitted by Fusarium fungi are EtOH, AcOH, (i) BuOH, 3-methylbutan-1-ol, 2-methylbutan-1-ol, ethyl 3-methylbutanoate, terpenes with M 136, sesquiterpenes with M 204 (a total of about 25), and trichodiene. It was found that the strains grown on PSA emit a wider spectrum and larger amount of VOCs compared with those grown on wheat kernels. F. langsethiae strain is the most active VOC producer on both substrates. The use of SPME and GC/MS also offers the potential for differentiation of fungal species and strains. PMID- 27253723 TI - Alexithymia, not autism, is associated with impaired interoception. AB - It has been proposed that Autism Spectrum Disorder (ASD) is associated with difficulties perceiving the internal state of one's body (i.e., impaired interoception), causing the socio-emotional deficits which are a diagnostic feature of the condition. However, research indicates that alexithymia - characterized by difficulties in recognizing emotions from internal bodily sensations - is also linked to atypical interoception. Elevated rates of alexithymia in the autistic population have been shown to underpin several socio emotional impairments thought to be symptomatic of ASD, raising the possibility that interoceptive difficulties in ASD are also due to co-occurring alexithymia. Following this line of inquiry, the present study examined the relative impact of alexithymia and autism on interoceptive accuracy (IA). Across two experiments, it was found that alexithymia, not autism, was associated with atypical interoception. Results indicate that interoceptive impairments should not be considered a feature of ASD, but instead due to co-occurring alexithymia. PMID- 27253725 TI - Aggregation of Heterogeneously Charged Colloids. AB - Patchy colloids are attractive as programmable building blocks for metamaterials. Inverse patchy colloids, in which a charged surface is decorated with patches of the opposite charge, are additionally noteworthy as models for heterogeneously charged biological materials such as proteins. We study the phases and aggregation behavior of a single charged patch in an oppositely charged colloid with a single-site model. This single-patch inverse patchy colloid model shows a large number of phases when varying patch size. For large patch sizes we find ferroelectric crystals, while small patch sizes produce cross-linked gels. Intermediate values produce monodisperse clusters and unusual worm structures that preserve finite ratios of area to volume. The polarization observed at large patch sizes is robust under extreme disorder in patch size and shape. We examine phase-temperature dependence and coexistence curves and find that large patch sizes produce polarized liquids, in contrast to mean-field predictions. Finally, we introduce small numbers of unpatched charged colloids. These can either suppress or encourage aggregation depending on their concentration and the size of the patches on the patched colloids. These effects can be exploited to control aggregation and to measure effective patch size. PMID- 27253724 TI - Neural mechanisms of goal-contingent task disengagement: Response-irrelevant stimuli activate the default mode network. AB - As we experience the world, we must decide not only when and how to act based on input from the environment, but also when to avoid responding in situations where acting could lead to a detrimental outcome. The ability to regulate behavior in this way requires flexible cognitive control, as the same stimulus may call for a response in one context but not in another. In this sense, explicit non responding can be characterized as an active, goal-directed cognitive process. Little is known about the mechanisms by which a currently active goal state modulates information processing to support the avoidance of undesired responding. In the present study, participants executed or withheld responses to a color target based whether its color matched that of a cue at the beginning of each trial. Behavioral and neural responses to task-irrelevant stimuli appearing as distractors were examined as a function of their relationship to the currently response-relevant color indicated by the cue. We observed a robust pattern in which stimuli possessing the currently response-irrelevant feature activate the default mode network (DMN), which was associated with a behavioral cost on trials in which this stimulus competed with a response-relevant target. Our findings reveal a role for the DMN in goal-directed cognitive control, facilitating active disengagement based on contextually-specific task demands. PMID- 27253726 TI - Determination of Interfacial Charge-Transfer Rate Constants in Perovskite Solar Cells. AB - A simple protocol to study the dynamics of charge transfer to selective contacts in perovskite solar cells, based on time-resolved laser spectroscopy studies, in which the effect of bimolecular electron-hole recombination has been eliminated, is proposed. Through the proposed procedure, the interfacial charge-transfer rate constants from methylammonium lead iodide perovskite to different contact materials can be determined. Hole transfer is faster for CuSCN (rate constant 0.20 ns(-1) ) than that for 2,2',7,7'-tetrakis-(N,N-di-4-methoxyphenylamino)-9,9' spirobifluorene (spiro-OMeTAD; 0.06 ns(-1) ), and electron transfer is faster for mesoporous (0.11 ns(-1) ) than that for compact (0.02 ns(-1) ) TiO2 layers. Despite more rapid charge separation, the photovoltaic performance of CuSCN cells is worse than that of spiro-OMeTAD cells; this is explained by faster charge recombination in CuSCN cells, as revealed by impedance spectroscopy. The proposed direction of studies should be one of the key strategies to explore efficient hole-selective contacts as an alternative to spiro-OMeTAD. PMID- 27253727 TI - Triple quantum filtered spectroscopy of homonuclear three spin-1/2 systems employing isotropic mixing. AB - We report the design and performance evaluation of novel pulse sequences for triple quantum filtered spectroscopy in homonuclear three spin-1/2 systems, employing isotropic mixing (IM) to excite triple quantum coherence (TQC). Our approach involves the generation of combination single quantum coherences (cSQC) from antisymmetric longitudinal or transverse magnetization components employing isotropic mixing (IM). cSQC's are then converted to TQC by a selective 180 degrees pulse on one of the spins. As IM ideally causes magnetization to evolve under the influence of the spin coupling Hamiltonian alone, TQC is generated at a faster rate compared to sequences involving free precession. This is expected to be significant when the spins have large relaxation rates. Our approach is demonstrated experimentally by TQC filtered 1D spectroscopy on a (1)H AX2 system (propargyl bromide in the presence of a paramagnetic additive), as well as a (31)P linear AMX system (ATP in agar gel). The performance of the IM-based sequences for TQC excitation are compared against the standard three pulse sequence (Ernst et al., 1987) and an AX2 spin pattern recognition sequence (Levitt and Ernst, 1983). The latter reaches the unitary bound on TQC preparation efficiency starting from thermal equilibrium in AX2 systems, not considering relaxation. It is shown that in systems where spins relax rapidly, the new IM based sequences indeed perform significantly better than the above two known TQC excitation sequences, the sensitivity enhancement being especially pronounced in the case of the proton system investigated. An overview of the differences in relaxation behavior is presented for the different approaches. Applications are envisaged to Overhauser DNP experiments and to in vivo NMR. PMID- 27253729 TI - Synthetic Glycosphingolipids for Live-Cell Labeling. AB - Glycosphingolipids are an important component of cell membranes that are involved in many biological processes. Fluorescently labeled glycosphingolipids are frequently used to gain insight into their localization. However, the attachment of a fluorophore to the glycan part or-more commonly-to the lipid part of glycosphingolipids is known to alter the biophysical properties and can perturb the biological function of the probe. Presented here is the synthesis of novel glycosphingolipid probes with mono- and disaccharide head groups and ceramide moieties containing fatty acids of varying chain length (C4 to C20). These glycosphingolipids bear an azide or an alkyne group as chemical reporter to which a fluorophore can be attached through a bioorthogonal ligation reaction. The fluorescent tag and any linker connected to it can be chosen in a flexible manner. We demonstrate the suitability of the probes by selective visualization of the plasma membrane of living cells by confocal microscopy techniques. Whereas the derivatives with the shorter fatty acids can be directly applied to HEK 293T cells, the hydrophobic glycosphingolipids with longer fatty acids can be delivered to cells using fusogenic liposomes. PMID- 27253728 TI - Drug Use on Mont Blanc: A Study Using Automated Urine Collection. AB - Mont Blanc, the summit of Western Europe, is a popular but demanding high altitude ascent. Drug use is thought to be widespread among climbers attempting this summit, not only to prevent altitude illnesses, but also to boost physical and/or psychological capacities. This practice may be unsafe in this remote alpine environment. However, robust data on medication during the ascent of Mont Blanc are lacking. Individual urine samples from male climbers using urinals in mountain refuges on access routes to Mont Blanc (Gouter and Cosmiques mountain huts) were blindly and anonymously collected using a hidden automatic sampler. Urine samples were screened for a wide range of drugs, including diuretics, glucocorticoids, stimulants, hypnotics and phosphodiesterase 5 (PDE-5) inhibitors. Out of 430 samples analyzed from both huts, 35.8% contained at least one drug. Diuretics (22.7%) and hypnotics (12.9%) were the most frequently detected drugs, while glucocorticoids (3.5%) and stimulants (3.1%) were less commonly detected. None of the samples contained PDE-5 inhibitors. Two substances were predominant: the diuretic acetazolamide (20.6%) and the hypnotic zolpidem (8.4%). Thirty three samples were found positive for at least two substances, the most frequent combination being acetazolamide and a hypnotic (2.1%). Based on a novel sampling technique, we demonstrate that about one third of the urine samples collected from a random sample of male climbers contained one or several drugs, suggesting frequent drug use amongst climbers ascending Mont Blanc. Our data suggest that medication primarily aims at mitigating the symptoms of altitude illnesses, rather than enhancing performance. In this hazardous environment, the relatively high prevalence of hypnotics must be highlighted, since these molecules may alter vigilance. PMID- 27253730 TI - Construction of a genetic linkage map and QTL analysis in bambara groundnut. AB - Bambara groundnut (Vigna subterranea (L.) Verdc.) is an indigenous underutilized legume that has the potential to improve food security in semi-arid Africa. So far, there are a lack of reports of controlled breeding populations that could be used for variety development and genetic studies. We report here the construction of the first genetic linkage map of bambara groundnut using a F3 population derived from a "narrow" cross between two domesticated landraces (Tiga Nicuru and DipC) with marked divergence in phenotypic traits. The map consists of 238 DArT array and SSR based markers in 21 linkage groups with a total genetic distance of 608.3 cM. In addition, phenotypic traits were evaluated for a quantitative trait loci (QTL) analysis over two generations. A total of 36 significant QTLs were detected for 19 traits. The phenotypic effect explained by a single QTL ranged from 11.6% to 49.9%. Two stable QTLs were mapped for internode length and growth habit. The identified QTLs could be useful for marker-assisted selection in bambara groundnut breeding programmes. PMID- 27253731 TI - Cell culture-adaptive mutations of NS5A affect replication of hepatitis C virus differentially depending on the viral genotypes. AB - Most of HCV RNAs require cell culture-adaptive mutations for efficient replication in cell culture and a number of such mutations have been described including a well-known S2204I substitution mutation in NS5A protein. In contrast, the replication of genotype 2a JFH1 RNA in cell culture does not require any cell culture-adaptive mutation. Rather, the presence of S2204I mutation impaired the JFH1 RNA replication. In this study, we examined the effect of reversions and substitutions of NS5A cell culture-adaptive mutations on virus replication in different genotypic backgrounds after either placing genotype 1a NS5A in the genotype 2a JFH1 or vice versa. The results from this investigation suggest that the S2204I mutation affects HCV RNA replication differentially depending on the viral genotypes but that the effect was not simply explained by the genotypic background. Perhaps, the effect of the S2204I mutation on HCV replication reflects both intra- and intergenic interactions of NS5A protein. J. Med. Virol. 89:146-152, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27253732 TI - Pharmacogenomic incidental findings in 308 families: The NIH Undiagnosed Diseases Program experience. AB - PURPOSE: Using single-nucleotide polymorphism (SNP) chip and exome sequence data from individuals participating in the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP), we evaluated the number and therapeutic informativeness of incidental pharmacogenetic variants. METHODS: Pharmacogenomics Knowledgebase (PharmGKB) annotated sequence variants were identified in 1,101 individuals. Medication records of participants were used to identify individuals prescribed medications with a genetic variant that might alter efficacy. RESULTS: A total of 395 sequence variants, including 19 PharmGKB 1A and 1B variants, were identified in SNP chip sequence data, and 388 variants, including 21 PharmGKB 1A and 1B variants, were identified in the exome sequence data. Nine participants had incidental pharmacogenetic variants associated with altered efficacy of a prescribed medication. CONCLUSIONS: Despite the small size of the NIH UDP patient cohort, we identified pharmacogenetic incidental findings potentially useful for guiding therapy. Consequently, groups conducting clinical genomic studies might consider reporting of pharmacogenetic incidental findings.Genet Med 18 12, 1303 1307. PMID- 27253733 TI - Results from an external proficiency testing program: 11 years of molecular genetics testing for myotonic dystrophy type 1. AB - PURPOSE: The aim of this study was to examine the performance of laboratories offering assessment for myotonic dystrophy type 1 (DM1) using external proficiency testing samples. DM1, a dominant disorder, has a prevalence of 1:20,000 due to the expansion of CTG trinucleotide repeats in the DMPK gene. METHODS: External proficiency testing administered by the College of American Pathologists/American College of Medical Genetics and Genomics distributes three samples twice yearly. Responses from 2003 through the first distribution of 2013 were analyzed after stratification by location (United States/international). Both the repeat sizes (analytic validity) and clinical interpretations were assessed. RESULTS: Over the 21 distributions, 45 US and 29 international laboratories participated. Analytic sensitivity for detecting and reporting expanded repeats (>=50) was 99.2% (382/385 challenges) and 97.1% (133/137 challenges), respectively. Analytic specificity (to within two repeats of the consensus) was 99.2% (1,790/1,805 alleles) and 98.6% (702/712 alleles), respectively. Clinical interpretations were correct for 99.3% (450/453) and 98.2% (224/228) of positive challenges and in 99.9% (936/937) and 99.6% (455/457) of negative challenges, respectively. Of four incorrect interpretations made in the United States, two were probably due to sample mix-up. CONCLUSION: This review of laboratory performance regarding laboratory-developed genetic tests indicates very high performance for both the analytic and interpretative challenges for DM1.Genet Med 18 12, 1290-1294. PMID- 27253734 TI - What are people willing to pay for whole-genome sequencing information, and who decides what they receive? AB - PURPOSE: Whole-genome sequencing (WGS) can be used as a powerful diagnostic tool as well as for screening, but it may lead to anxiety, unnecessary testing, and overtreatment. Current guidelines suggest reporting clinically actionable secondary findings when diagnostic testing is performed. We examined preferences for receiving WGS results. METHODS: A US nationally representative survey (n = 410 adults) was used to rank preferences for who decides (an expert panel, your doctor, you) which WGS results are reported. We estimated the value of information about variants with varying levels of clinical usefulness by using willingness to pay contingent valuation questions. RESULTS: The results were as follows: 43% preferred to decide themselves what information is included in the WGS report. 38% (95% confidence interval (CI): 33-43%) would not pay for actionable variants, and 3% (95% CI: 1-5%) would pay more than $1,000. 55% (95% CI: 50-60%) would not pay for variants for which medical treatment is currently unclear, and 7% (95% CI: 5-9%) would pay more than $400. CONCLUSION: Most people prefer to decide what WGS results are reported. Despite valuing actionable information more, some respondents perceive that genetic information could negatively impact them. Preference heterogeneity for WGS information should be considered in the development of policies, particularly to integrate patient preferences with personalized medicine and shared decision making.Genet Med 18 12, 1295-1302. PMID- 27253736 TI - Radical Changes in Lewis Acid Catalysis: Matching Metal and Substrate. AB - Whereas the stereochemical rigidity of the coordination sphere of boxmi/Cu(II) catalysts is key to achieving high enantioselectivity in the electrophilic alkylation of beta-ketoesters, this pathway is outperformed by a radical process for the corresponding catalytic transformation of oxindoles, giving rise to racemic products. For the corresponding Zn(II) catalysts, the selectivity in the latter process is outstanding despite the greater plasticity of the coordination shell. This reaction was thus developed into a highly useful synthetic method, which enabled the conversion of wide range of substrates with high yields and enantioselectivities. PMID- 27253735 TI - "Missing Tooth" Multidomain Peptide Nanofibers for Delivery of Small Molecule Drugs. AB - The clinical administration of many small molecule hydrophobic drugs is challenged by the insolubility of these drugs under physiological conditions. Because of this, the development of biocompatible scaffolds capable of effectively delivering hydrophobic drug molecules is of particular interest. Multidomain peptides (MDPs) provide biocompatible hydrogel scaffolds that are injectable and space-conforming, allowing for in situ delivery of a variety of drugs. Here we demonstrate that through manipulation of peptide primary sequence, a molecular cavity can be incorporated into the hydrophobic core of these peptide nanofibers allowing for encapsulation and delivery of small molecule drugs with poor water solubility. Using SN-38, daunorubicin, diflunisal, etodolac, levofloxacin, and norfloxacin, we demonstrate drug encapsulation and release from multidomain peptide fibers. Steady-state fluorescence and drug release studies show that hydrogels loaded with SN-38, diflunisal, and etodolac exhibit prolonged drug release profiles due to intrafibrillar drug encapsulation. This study establishes multidomain peptides as promising carriers for localized in situ delivery of small molecule drugs with poor water solubility. PMID- 27253737 TI - Treatment of Regional Lymph Nodes in Breast Cancer-Not Recommended for All Patients With 1 to 3 Positive Auxiliary Nodes. PMID- 27253738 TI - PREVALENCE OF BACTERIAL RESISTANCE IN HOSPITALIZED CIRRHOTIC PATIENTS IN SOUTHERN BRAZIL: A NEW CHALLENGE. AB - BACKGROUND & AIMS: An increased frequency of infections by multiresistant bacteria has been described in hospitalized patients. The aim of this study was to evaluate the bacterial resistance profile in cirrhotic patients. METHODS: This is a retrospective observational study. We assessed the antimicrobial susceptibility of 5,839 bacterial isolates from patients with and without cirrhosis. Regarding the multidrug resistance, we evaluated 4,505 bacterial isolates from 2,180 patients. RESULTS: Two hundred and fifty-one patients had cirrhosis (mean age 57.6 +/- 11 years; 61.8% were male, 47.8% of cases associated with hepatitis C virus). Of the isolates of patients with and without cirrhosis, 174/464 (37.5%) and 1,783/4,041 (44.1%) were multiresistant, respectively (p = 0.007). E. coli was the most common multiresistant bacteria in both groups. Approximately 20% of E. coli and Klebsiella sp. isolates were ESBL-producers and 44% of S. aureus isolates were methicillin-resistant in cirrhotic patients. In cirrhotic patients admitted to the emergency department, hospital ward, and intensive care unit, 28.3%, 50% and 40% had multiresistant isolates, respectively. In patients with and without cirrhosis, 36.2% and 33.5% of isolates were resistant to third-generation cephalosporins, respectively. CONCLUSIONS: The empirical treatment of infections in hospitalized patients using broad-spectrum antibiotics should consider the observed pattern of bacterial resistance. PMID- 27253739 TI - IMPACT OF THE PEGYLATED-INTERFERON AND RIBAVIRIN THERAPY ON THE TREATMENT-RELATED MORTALITY OF PATIENTS WITH CIRRHOSIS DUE TO HEPATITIS C VIRUS. AB - Although the protease inhibitors have revolutionized the therapy of chronic hepatitis C (CHC), the concomitant use of pegylated-interferon (PEG-IFN) and ribavirin (RBV) is associated to a high rate of adverse effects. In this study, we evaluated the consequences of PEG-IFN and RBV and their relationship with mortality in patients with cirrhosis. METHODS: Medical records of CHC who underwent treatment with PEG-IFN and RBV in a public hospital in Brazil were evaluated. All the patients with cirrhosis were selected, and their clinical and laboratory characteristics, response to treatment, side effects and mortality were evaluated. RESULTS: From the 1,059 patients with CHC, 257 cirrhotic patients were evaluated. Of these, 45 (17.5%) achieved sustained viral response (SVR). Early discontinuation of therapy occurred in 105 (40.8%) patients, of which 39 (15.2%) were due to serious adverse effects. The mortality rate among the 257 cirrhotic patients was 4.3%, occurring in 06/242 (2.4%) of the Child-A, and in 05/15 (33.3%) of the Child-B patients. In conclusion, the treatment of patients with cirrhosis due to HCV with PEG-IFN and RBV shows a low SVR rate and a high mortality, especially in patients with liver dysfunction. PMID- 27253741 TI - ANTHELMINTIC ACTIVITY OF CHLOROPHYLLIN AGAINST DIFFERENT LARVAL STAGES OF Fasciola gigantica. AB - Fasciolosis is a food borne zoonosis, caused by the digenetic trematode Fasciola. Freshwater lymnaeid snails are the intermediate host of the trematodes. Chlorophyllin, a semi-synthetic derivative of chlorophyll and its formulations obtained from freeze dried cow urine (FCU) had their toxicity tested against redia and cercaria larvae of F. gigantica. The larvicidal activity of chlorophyllin and its formulations were found to depend on both, time and concentration used against the larvae. Toxicity of chlorophyllin + FCU (1:1 ratio) in sunlight against redia larva (8 h LC50: 0.03 mg/mL) was more pronounced than using just chlorophyllin (8 h LC50: 0.06 mg/mL). Toxicity of chlorophyllin + FCU in sunlight against redia (8 h LC50: 0.03 mg/mL) was higher than against cercaria (8 h LC50: 0.06 mg/mL). The larvicidal activity of chlorophyllin in sunlight (redia/cercaria larvae: 8 h LC50: 0.06 mg/mL) was more pronounced than under laboratory conditions (redia: 8 h LC50: 22.21 mg/mL/, cercaria 8 h LC50: 96.21 mg/mL). Toxicity of FCU against both larvae was lower than that of chlorophyllin and chlorophyllin + FCU. Chlorophyllin and its formulations + FCU were 357.4 to 1603.5 times more effective against redia/cercaria larvae in sunlight than under laboratory conditions. The present study has shown that chlorophyllin formulations may be used as potent larvicides against fasciolosis. PMID- 27253740 TI - Echinococcus granulosus sensu lato GENOTYPES IN DOMESTIC LIVESTOCK AND HUMANS IN GOLESTAN PROVINCE, IRAN. AB - Cystic echinococcosis (CE) is a globally parasitic zoonosis caused by larval stages of Echinococcus granulosus. This study investigated E. granulosus genotypes isolated from livestock and humans in the Golestan province, northern Iran, southeast of the Caspian sea, using partial sequencing data of the cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase 1 (nad1) mitochondrial genes. Seventy E. granulosus isolates were collected from animals in slaughterhouses: 18 isolates from sheep, 40 from cattle, nine from camels, two from buffaloes and one from a goat, along with four human isolates (formalin fixed, paraffin-embedded tissues) from CE patients of provincial hospitals. All isolates were successfully analysed by PCR amplification and sequencing. The sequence analysis found four E. granulosus genotypes among the 74 CE isolates: G1 (78.3%), G2 (2.7%), G3 (15%) and G6 (4%). The G1-G3 complex genotype was found in all of the sheep, goat, cattle and buffalo isolates. Among the nine camel isolates, the frequency of G1-G3 and G6 genotypes were 66.7% and 33.3%, respectively. All four human CE isolates belonged to E. granulosus sensu stricto. This study reports the first occurrence of the G2 genotype in cattle from Iran and confirms the previously reported G3 genotype in camels in the same country. PMID- 27253742 TI - EPIDEMIOLOGY OF HONEYBEE STING CASES IN THE STATE OF CEARA, NORTHEASTERN BRAZIL. AB - In the American continent, honeybee envenomation is a public health problem due to the high incidence and severity of the cases. Despite its medical importance, there is a lack of epidemiological studies on this topic in Brazil, especially referring to the Northeastern states. The present study has aimed to describe the epidemiological features of honeybee envenomation cases in the state of the Ceara, Northeastern Brazil, from 2007 to 2013. Data were collected from the Injury Notification Information System database of the Health Department of Ceara. A total of 1,307 cases were analyzed. Cases were shown to be distributed in all the months of the studied years, reaching higher frequencies in August. The majority of cases occurred in urban areas and involved men aged between 20 and 29 years. Victims were mainly stung on the head and torso, and they received medical assistance predominantly within 3 hours after being stung. Local manifestations were more frequent than systemic ones. Most cases were classified as mild and progressed to cure. The high number of honeybee sting cases shows that Ceara may be an important risk area for such injuries. Moreover, the current study provides data for the development of strategies to promote control and prevention of bee stings in this area. PMID- 27253743 TI - PERFORMANCE OF CONVENTIONAL PCRs BASED ON PRIMERS DIRECTED TO NUCLEAR AND MITOCHONDRIAL GENES FOR THE DETECTION AND IDENTIFICATION OF Leishmania spp. AB - In visceral leishmaniasis, the detection of the agent is of paramount importance to identify reservoirs of infection. Here, we evaluated the diagnostic attributes of PCRs based on primers directed to cytochrome-B (cytB), cytochrome-oxidase subunit II (coxII), cytochrome-C (cytC), and the minicircle-kDNA. Although PCRs directed to cytB, coxII, cytC were able to detect different species of Leishmania, and the nucleotide sequence of their amplicons allowed the unequivocal differentiation of species, the analytical and diagnostic sensitivity of these PCRs were much lower than the analytical and diagnostic sensitivity of the kDNA-PCR. Among the 73 seropositive animals, the asymptomatic dogs had spleen and bone marrow samples collected and tested; only two animals were positive by PCRs based on cytB, coxII, and cytC, whereas 18 were positive by the kDNA-PCR. Considering the kDNA-PCR results, six dogs had positive spleen and bone marrow samples, eight dogs had positive bone marrow results but negative results in spleen samples and, in four dogs, the reverse situation occurred. We concluded that PCRs based on cytB, coxII, and cytC can be useful tools to identify Leishmania species when used in combination with automated sequencing. The discordance between the results of the kDNA-PCR in bone marrow and spleen samples may indicate that conventional PCR lacks sensitivity for the detection of infected dogs. Thus, primers based on the kDNA should be preferred for the screening of infected dogs. PMID- 27253744 TI - PREVALENCE, RISK FACTORS AND SYMPTOMS ASSOCIATED TO INTESTINAL PARASITE INFECTIONS AMONG PATIENTS WITH GASTROINTESTINAL DISORDERS IN NAHAVAND, WESTERN IRAN. AB - We studied the prevalence of intestinal parasites (IPs), their risk factors and associated symptoms among patients with gastrointestinal disorders. A total of 1,301 participants aged 22 days-90 years were enrolled in this study. We used a structured questionnaire to obtain socio-demographic and stool examination to investigate intestinal parasite infections. Data analysis was performed using SPSS16. The overall prevalence of intestinal parasites (IPs) was 32.2% (419/1,301). Three hundred and fifty nine cases/1,301 (27.6%) were infected with a single parasite and 60/1,301 cases (4.6%) presented polyparasitism. The most common IP was Blastocystis sp. 350/1,301 (26.9%), followed by Entamoeba coli 38/1,301 (2.92%), Giardia lamblia 30/1,301 (2.3%) and Cryptosporidium spp. 17/1,301 (1.3%). Regarding the socio-demographic variables, educational status (p = 0.001), contact with domestic animals and soil (p = 0.02), age above 15 years (p = 0.001) and seasons (p = 0.001) were significantly associated to intestinal parasitic infections. Concerning clinical characteristics, the presence of IPs was significantly associated to diarrhea (OR = 1.57; CI 95% = 1.24-1.98; p < 0.001) and dysentery (OR = 1.94; CI 95% = 1.03-3.66; p < 0.04). Our findings suggest that IPs are one of the main causal agents of gastrointestinal disorders. Improving the knowledge on local risk factors such as poverty, low level of education, poor sanitation, contact with soil and contact with domestic animal is warranted. PMID- 27253745 TI - EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE. AB - Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions. PMID- 27253746 TI - EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS. AB - Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity) and eggs hatchability (fertility) in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors. PMID- 27253747 TI - THE PROCESS OF Leishmania INFECTION - DISEASE AND NEW PERSPECTIVES OF PALEOPARASITOLOGY. AB - Species of the genus Leishmania (Kinetoplastida, Trypanosomatidae) are causative agents of leishmaniasis, a complex disease with variable clinical spectrum and epidemiological diversity, constituting, in some countries, a serious public health problem. The origin and evolution of leishmaniasis has been under discussion regarding some clinical and parasitological aspects. After the introduction of paleoparasitology, molecular methods and immunodiagnostic techniques have been applied allowing the recovery of parasite remains, as well as the diagnosis of past infections in humans and other hosts. The dating of archaeological samples has allowed the parasitological analysis in time and space. This manuscript presents the state of the art of leishmaniasis and prospects related to paleoparasitology studies and their contribution to the evolutionary and phylogenetic clarification of parasites belonging to the genus Leishmania, and the leishmaniasis caused by them. PMID- 27253748 TI - OCULAR SYPHILIS IN A KIDNEY TRANSPLANT RECIPIENT. AB - We present a case of ocular syphilis after a renal transplantation involving progressive vision loss without clinically identifiable ocular disease. Electroretinography showed signs of ischemia, especially in the internal retina. A serological test was positive for syphilis. Lumbar puncture revealed lymphocytic meningitis and a positive serologic test for syphilis in the cerebrospinal fluid. The patient was treated with penicillin, and had a quick vision improvement. In the case of transplant recipients, clinicians should always consider the diagnosis of ocular syphilis in cases with unexplained visual acuity decrement, as this condition may cause serious complications if not treated. PMID- 27253749 TI - BIOFILM FORMATION OF Vibrio cholerae ON STAINLESS STEEL USED IN FOOD PROCESSING. AB - Vibrio cholerae represents a significant threat to human health in developing countries. This pathogen forms biofilms which favors its attachment to surfaces and its survival and transmission by water or food. This work evaluated the in vitro biofilm formation of V. cholerae isolated from clinical and environmental sources on stainless steel of the type used in food processing by using the environmental scanning electron microscopy (ESEM). Results showed no cell adhesion at 4 h and scarce surface colonization at 24 h. Biofilms from the environmental strain were observed at 48 h with high cellular aggregations embedded in Vibrio exopolysaccharide (VPS), while less confluence and VPS production with microcolonies of elongated cells were observed in biofilms produced by the clinical strain. At 96 h the biofilms of the environmental strain were released from the surface leaving coccoid cells and residual structures, whereas biofilms of the clinical strain formed highly organized structures such as channels, mushroom-like and pillars. This is the first study that has shown the in vitro ability of V. cholerae to colonize and form biofilms on stainless steel used in food processing. PMID- 27253750 TI - Real-Time Structural and Electrical Characterization of Metal-Insulator Transition in Strain-Modulated Single-Phase VO2 Wires with Controlled Diameters. AB - Single-crystal VO2 wires have gained tremendous popularity for enabling the study of the fundamental properties of the metal-insulator transition (MIT); however, it remains tricky to precisely measure the intrinsic properties of the transitional phases with controlled wire-growth properties, such as diameter. Here, we report a facile method for growing VO2 wires with controlled diameters by separating the formation of the liquidus V2O5 seed droplets from the evolution of the VO2 wire using oxygen gas. The kinetic analyses suggest that the growth proceeds via the VS (vapor-solid) mechanism, whereas the droplet determines the size and the location of the wire. In situ Raman spectroscopy combined with analyses of the electrical properties of an individual wire allowed us to construct a diameter-temperature phase diagram from three initial phases (i.e., M1, T, and M2), which were created by misfit stress from the substrate and were preserved at room temperature. We also correlated this relation with resistivity diameter and activation energy-diameter relations supported by theoretical modeling. These carefully designed approaches enabled us to elucidate the details of the phase transitions over a wide range of stress conditions, offering an opportunity to quantify relevant thermodynamic and electronic parameters (including resistivities, activation energies, and energy barriers of the key insulating phases) and to explain the intriguing behaviors of the T phase during the MIT. PMID- 27253752 TI - New boron based salts for lithium-ion batteries using conjugated ligands. AB - A new anion design concept, based on combining a boron atom as the central atom and conjugated systems as ligands, is presented as a route for finding alternative Li-salts for lithium-ion batteries. The properties of a wide range of novel anions designed in this way have been evaluated by DFT calculations focusing on three different fundamental success factors/measures: the strength of the cation-anion interaction, ultimately determining both the solubility and the ionic conductivity, the oxidation limit, determining their possible use vs. high voltage cathodes, and the reduction stability, revealing a possible role of the anion in the SEI-formation at the anode. For a few anions superior properties vs. today's existing or suggested anions are predicted, especially the very low cation-anion interaction strengths are promising features. The design route itself is shown to be versatile in determining the correlation between different choices of ligands and the resulting overall properties - where the most striking feature is the decreased lithium cation interaction energy upon using the (1Z,3Z) buta-1,3-diene-1,2,3,4-tetracarbonitrile ligands. This also opens avenues for the further design of novel anions beyond those with a boron central atom. PMID- 27253751 TI - Interstitial Fluid Glucose Is Not Just a Shifted-in-Time but a Distorted Mirror of Blood Glucose: Insight from an In Silico Study. AB - BACKGROUND: Glucose sensors measure glucose concentration in the interstitial fluid (ISF), remote from blood. ISF glucose is well known to be "delayed" with respect to blood glucose (BG). However, ISF glucose is not simply a shifted-in time version of BG but exhibits a more complex pattern. METHODS: To gain insight into this problem, one can use linear systems theory. However, this may lose a more clinical readership, thus we use simulation and two case studies to convey our thinking in an easier way. In particular, we consider BG concentration measured after meal and exercise in 12 healthy volunteers, whereas ISF glucose is simulated using a well-accepted model of blood-ISF glucose kinetics, which permits calculation of the equilibration time, a parameter characterizing the system. Two metrics are defined: blood and ISF glucose difference at each time point and time to reach the same glucose value in blood and ISF. RESULTS: The simulation performed and the two metrics show that the relationship between blood ISF glucose profiles is more complex than a pure shift in time and that the pattern depends on both equilibration time and BG. CONCLUSIONS: In this in silico study, we have illustrated, with simple case studies, the meaning of the of ISF glucose with respect to BG. Understanding that ISF glucose is not just a shifted in-time version but a distorted mirror of BG is important for a correct use of continuous glucose monitoring for diabetes management. PMID- 27253753 TI - Reduced expression of the DNA glycosylase gene MUTYH is associated with an increased number of somatic mutations via a reduction in the DNA repair capacity in prostate adenocarcinoma. AB - 8-Hydroxyguanine (8OHG), a major oxidative DNA lesion, is known to accumulate in prostate cancer; however, the status of one of its repair enzymes, MUTYH, in prostate cancer remains to be elucidated. In this study, we showed that the expression levels of MUTYH mRNA and protein were significantly lower in prostate cancer than in non-cancerous prostatic tissue by examining two independent, publicly available databases and by performing an immunohistochemical analysis of prostate cancer specimens obtained at our hospital, respectively. About two thirds of the prostate cancers exhibited a reduced MUTYH expression. When the effect of reduced MUTYH expression in prostate adenocarcinoma on the somatic mutation load was examined using data from the Cancer Genome Atlas (TCGA) database, the numbers of total somatic mutations and somatic G:C to T:A mutations were significantly higher in the reduced MUTYH expression group than in the other group (P < 0.0001 and P = 0.0013, respectively). To determine the reason why reduced MUTYH expression leads to somatic mutation loads in prostate adenocarcinoma, we compared the DNA repair capacities between PC-3 prostatic cell line derived clones with different MUTYH expression levels. Both the capacities to cleave DNA containing adenine:8OHG mispairs and to suppress mutations caused by 8OHG were significantly lower in prostatic cell lines with lower MUTYH expression than in prostatic cell lines with higher MUTYH expression. These results suggested that reduced MUTYH expression is associated with somatic mutation loads via a reduction in DNA repair capacity in prostate adenocarcinoma. (c) 2016 Wiley Periodicals, Inc. PMID- 27253754 TI - Cigarette Smoking Among Urban American Indian Adults - Hennepin and Ramsey Counties, Minnesota, 2011. AB - In 2013, it was estimated that the prevalence of cigarette smoking among American Indians was 36.5%, the highest of all racial/ethnic groups in the continental United States (1). Among American Indians, considerable cultural and geographic variation in cigarette smoking exists. Smoking prevalence among American Indians is lowest in the Southwest and highest in the Upper Midwest/Northern Plains (2). Little information is available about tobacco use among urban American Indians, who might not have ever lived on a reservation or be enrolled in or affiliated with a tribe. In Minnesota, a significant proportion of American Indians reside in urban areas. Among Minnesota's residents who identify as American Indian alone or in combination with another race, 30% live in Hennepin County and Ramsey County, which encompass Minneapolis and St. Paul, respectively (collectively known as the Twin Cities). The predominant tribes (Ojibwe [Chippewa] and Dakota/Lakota/Nakota [Sioux]) traditionally have used locally grown tobacco (Nicotiana rustica), red willow, and other plants for religious ceremonies, although nonceremonial tobacco is often substituted for traditional plants. To assess prevalence of cigarette smoking among this population, it is important to distinguish ceremonial tobacco use (smoked or used in other ways) from nonceremonial tobacco use. To obtain estimates of cigarette smoking prevalence among American Indians in Hennepin and Ramsey counties, the American Indian Adult Tobacco Survey was administered to 964 American Indian residents in 2011, using respondent-driven sampling. Among all participants, 59% were current smokers, 19% were former smokers, and 22% had never smoked. Approximately 40% of employed participants reported that someone smoked in their workplace area during the preceding week. High prevalences of cigarette smoking and secondhand smoke exposure among urban American Indians in Minnesota underscores the need for a comprehensive and culturally appropriate approach to reducing nonceremonial tobacco use. PMID- 27253755 TI - An extractive membrane biofilm reactor as alternative technology for the treatment of methyl tert-butyl ether contaminated water. AB - Among the strategies developed for contaminated groundwater bioremediation, those based on the use of bacteria adhering to inert supports and establishing biofilms have gained great importance in this field. Extractive membrane biofilm reactor (EMBFR) technology offers productive solutions for the removal of volatile and semi-volatile compounds. EMBFR technology is based on the use of extractive semipermeable membranes through which contaminants migrate to the biological compartment in which microorganisms with pollutant biotransformation and/or mineralization capacities can grow, forming an active biofilm on the membrane surface. The objective of this study was to assess the use of three bacterial strains (Paenibacillus sp. SH7 CECT 8558, Agrobacterium sp. MS2 CECT 8557, and Rhodococcus ruber EE6 CECT 8612), as inoculum in a lab-scale EMBFR running for 28 days under aerobic conditions to eliminate methyl tert-butyl ether (MTBE) from water samples. Three different hydraulic retention times (1, 6, and 12 h) were employed. MTBE degradation values were determined daily by a gas GC-MS technique, as well as suspended bacterial growth. The biofilm established by the bacterial strains on the semipermeable membrane was detected by Field-Emission Scanning Electron Microscopy (FESEM) at the end of each experiment. The acute toxicity of the treated effluents and biomedium was determined by Microtox(c) assay (EC50 ).The results achieved from the MTBE degradation, biofilm formation, and toxicity analysis indicated that bacterial strains MS2 and EE6 were the best options as selective inoculum, although further research is needed, particularly with regard to their possible use as a mixed culture. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1238-1245, 2016. PMID- 27253756 TI - Protein-protein structure prediction by scoring molecular dynamics trajectories of putative poses. AB - The prediction of protein-protein interactions and their structural configuration remains a largely unsolved problem. Most of the algorithms aimed at finding the native conformation of a protein complex starting from the structure of its monomers are based on searching the structure corresponding to the global minimum of a suitable scoring function. However, protein complexes are often highly flexible, with mobile side chains and transient contacts due to thermal fluctuations. Flexibility can be neglected if one aims at finding quickly the approximate structure of the native complex, but may play a role in structure refinement, and in discriminating solutions characterized by similar scores. We here benchmark the capability of some state-of-the-art scoring functions (BACH SixthSense, PIE/PISA and Rosetta) in discriminating finite-temperature ensembles of structures corresponding to the native state and to non-native configurations. We produce the ensembles by running thousands of molecular dynamics simulations in explicit solvent starting from poses generated by rigid docking and optimized in vacuum. We find that while Rosetta outperformed the other two scoring functions in scoring the structures in vacuum, BACH-SixthSense and PIE/PISA perform better in distinguishing near-native ensembles of structures generated by molecular dynamics in explicit solvent. Proteins 2016; 84:1312-1320. (c) 2016 Wiley Periodicals, Inc. PMID- 27253757 TI - Thymol-based submicron emulsions exhibit antifungal activity against Fusarium graminearum and inhibit Fusarium head blight in wheat. AB - AIMS: Fusarium graminearum is a very destructive fungal pathogen that leads to Fusarium head blight (FHB) in wheat, a disease which costs growers millions of dollars annually both in crop losses and in remediation efforts. Current countermeasures include the deployment of wheat varieties with some resistance to FHB in conjunction with timed fungicide treatments. In this article, we introduce a fungicide based on thymol, a naturally occurring plant phenolic derived from essential oils. To overcome the hydrophobicity of thymol, the thymol active was incorporated into a low-surfactant submicron emulsion with and without a carrier oil. METHODS AND RESULTS: The minimum fungicidal concentration of F. graminearum was found to be both 0.02% for thymol emulsions with and without an oil component. Time-to-kill experiments showed that thymol emulsions were able to inactivate F. graminearum in as little as 10 s at concentrations above 0.06%. Spraying the thymol emulsions (~0.1% range) on the wheat variety Bobwhite demonstrated significant reductions in FHB infection rate (number of infected spikelets). However, with 0.5% thymol, the wheat heads exhibited premature senescence. Transmission and scanning electron micrographs suggest that the mechanism of antifungal action is membrane mediated, as conidia exposed to thymol showed complete organelle disorganization and evidence of lipid emulsification. CONCLUSION: The collective experimental data suggest that thymol emulsions may be an effective naturally derived alternative to the current thymol treatments, and chemical fungicides in ameliorating FHB. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first thymol-derived nanoemulsion particles resuspended into water and not DMSO, exhibiting the same antibacterial/antifungal activity as previously described thymol and thyme oil treatments. This drastically reduces the environmental footprint thymol will leave if utilized as a fungicide treatment on field crops. PMID- 27253758 TI - Scanning the Horizon. PMID- 27253759 TI - Corrigendum: Stiffness in vortex-like structures due to chirality-domains within a coupled helical rare-earth superlattice. PMID- 27253760 TI - Microperimetry Features of Geographic Atrophy Identified With En Face Optical Coherence Tomography. AB - IMPORTANCE: Progressive geographic atrophy (GA) of the retinal pigment epithelium leads to loss of central vision. To identify GA in age-related macular degeneration and assess treatment, correlation of function observed on microperimetry with structure observed on optical coherence tomographic (OCT) images may be of value. OBJECTIVE: To characterize the microperimetric function of GA as identified from en face OCT imaging. DESIGN, SETTING, AND PARTICIPANTS: In a case-series study, 20 patients (22 eyes) entered the study at the University of Padova according to preplanned conditions. From March 1 to July 30, 2014, en face OCT images were obtained at the outer retinal layer and choroidal layer levels. The microperimetry sensitivity map was superimposed on the en face OCT images, which had been used to measure GA areas. Relative and dense scotoma rates were calculated in the GA areas. After data collection, the study eyes were divided into 3 groups according to the macular residual mean sensitivity. MAIN OUTCOMES AND MEASURES: Retinal sensitivity measured by microperimetry within areas of GA identified by en face OCT images. RESULTS: Twenty patients (5 men and 15 women) were included in the study, with a mean (SD) age of 79.5 (7.0) years (range, 69-98 years). Macular residual mean retinal sensitivity was less than 5 dB in 7 eyes (group 1), 5 to 10 dB in 9 eyes (group 2), and greater than 10 dB in 6 eyes (group 3). Mean (SD) GA area differed among the groups at the outer retinal (13.13 [5.03] mm2 [range, 5.75-21.04 mm2] in group 1; 7.80 [3.25] mm2 [range, 3.31-13.52 mm2] in group 2; and 3.94 [2.35] mm2 [range, 1.46-7.90 mm2] in group 3; P = .001) and choroidal (11.83 [5.55] mm2 [range, 4.55-22.14 mm2] in group 1; 7.00 [4.29] mm2 [range, 0.90-13.83 mm2] in group 2; and 3.27 [2.29] mm2 [range, 0.91-7.23 mm2] in group 3; P = .007) layer levels. Mean (SD) GA area imaged at the outer retinal layer level was significantly larger than that imaged at the choroidal level in group 3 (difference, 0.67 mm2; 95% CI, 0.31-1.03 mm2; P = .005), but not in groups 1 or 2. Mean (SD) rate of relative scotoma was significantly higher in the GA area imaged at the outer retinal layer level than at the choroidal level in group 3 (47.70% [31.30%] [range, 13.60%-100%] vs 34.00% [37.30%] [range, 0%-100%]; difference, 13.74%; 95% CI, 3.84%-23.63%; P = .02), but not in groups 1 or 2. CONCLUSIONS AND RELEVANCE: In the early stage of GA, when retinal sensitivity is relatively good, these data suggest that the GA area imaged on en face OCT at the outer retinal level correctly detects the wide functional degenerative involvement of the photoreceptors. These findings provide novel data that correlate function and structure, which may be of value when assessing treatments that might prevent or reduce the rate of growth of GA. PMID- 27253761 TI - A comparison of self-reported quality of life for an Australian haemodialysis and haemodiafiltration cohort. AB - AIMS: Haemodiafiltration (HDF) has been widely studied for evidence of superior outcomes in comparison with conventional haemodialysis (HD), and there is increasing interest in determining if HDF confers any benefit in relation to quality of life. Studies have been conducted with randomized incident patients; however, little is known regarding HDF and quality of life for prevalent patients. This study examined and compared self-reported quality of life at two time points, 12 months apart in a cohort of satellite HD and HDF patients, using a disease specific questionnaire to determine if HDF conferred an advantage. METHODS: A longitudinal study with a linear mixed-effect model measuring quality of life in a cohort of 171 patients (HD, n = 85, HDF, n = 86) in seven South Australian satellite dialysis centres. RESULTS: Factors associated with significant reduction across the Kidney Disease Quality Of LifeTM domains measured were younger age (- 20 to - 29) and comorbid diabetes (- 4.8 to - 11.1). HDF was not associated with moderation of this reduction at either time point (P > 0.05). Baseline physical functioning was reported as very low (median 33.9) and further reduced at time point two. In addition, dialysing for more than 12 h per week in a satellite dialysis unit was associated with reduced quality of life in relation to the burden of kidney disease (- 13.69). CONCLUSION: This study has demonstrated that younger age and comorbid diabetes were responsible for a statistically significant reduction in quality of life, and HDF did not confer any advantage. PMID- 27253762 TI - A Highly Photostable Hyperbranched Polyglycerol-Based NIR Fluorescence Nanoplatform for Mitochondria-Specific Cell Imaging. AB - Considering the critical role of mitochondria in the life and death of cells, non invasive long-term tracking of mitochondria has attracted considerable interest. However, a high-performance mitochondria-specific labeling probe with high photostability is still lacking. Herein a highly photostable hyperbranched polyglycerol (hPG)-based near-infrared (NIR) quantum dots (QDs) nanoplatform is reported for mitochondria-specific cell imaging. Comprising NIR Zn-Cu-In-S/ZnS QDs as extremely photostable fluorescent labels and alkyl chain (C12 )/triphenylphosphonium (TPP)-functionalized hPG derivatives as protective shell, the tailored QDs@hPG-C12 /TPP nanoprobe with a hydrodynamic diameter of about 65 nm exhibits NIR fluorescence, excellent biocompatibility, good stability, and mitochondria-targeted ability. Cell uptake experiments demonstrate that QDs@hPG C12 /TPP displays a significantly enhanced uptake in HeLa cells compared to nontargeted QDs@hPG-C12 . Further co-localization study indicates that the probe selectively targets mitochondria. Importantly, compared with commercial deep-red mitochondria dyes, QDs@hPG-C12 /TPP possesses superior photostability under continuous laser irradiation, indicating great potential for long-term mitochondria labeling and tracking. Moreover, drug-loaded QDs@hPG-C12 /TPP display an enhanced tumor cell killing efficacy compared to nontargeted drugs. This work could open the door to the construction of organelle-targeted multifunctional nanoplatforms for precise diagnosis and high-efficient tumor therapy. PMID- 27253763 TI - Age-Related Differences in Sleep Architecture and Electroencephalogram in Adolescents in the National Consortium on Alcohol and Neurodevelopment in Adolescence Sample. AB - STUDY OBJECTIVES: To investigate age-related differences in polysomnographic and sleep electroencephalographic (EEG) measures, considering sex, pubertal stage, ethnicity, and scalp topography in a large group of adolescents in the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). METHODS: Following an adaptation/clinical screening night, 141 healthy adolescents (12-21 y, 64 girls) had polysomnographic recordings, from which sleep staging and EEG measures were derived. The setting was the SRI International Human Sleep Laboratory and University of Pittsburgh Pediatric Sleep Laboratory. RESULTS: Older age was associated with a lower percentage of N3 sleep, accompanied by higher percentages of N2, N1, and rapid eye movement (REM) sleep. Older boys compared with younger boys had more frequent awakenings and wakefulness after sleep onset, effects that were absent in girls. Delta (0.3-4 Hz) EEG power in nonrapid eye movement NREM sleep was lower in older than younger adolescents at all electrode sites, with steeper slopes of decline over the occipital scalp. EEG power in higher frequency bands was also lower in older adolescents than younger adolescents, with equal effects across electrodes. Percent delta power in the first NREM period was similar across age. African Americans had lower EEG power across frequency bands (delta to sigma) compared with Caucasians. Finally, replacing age with pubertal status in the models showed similar relationships. CONCLUSIONS: Substantial differences in sleep architecture and EEG were evident across adolescence in this large group, with sex modifying some relationships. Establishment and follow-up of this cohort allows the investigation of sleep EEG brain structural relationships and the effect of behaviors, such as alcohol and substance use, on sleep EEG maturation. PMID- 27253764 TI - Upper Airway Vibration Perception in School-Aged Children with Obstructive Sleep Apnea. AB - STUDY OBJECTIVES: Children with the obstructive sleep apnea (OSA) have impaired upper airway two-point discrimination compared to controls. In addition, blunted vibration threshold detection (VT) in the palate has been recognized in adults with OSA, but has not been studied in children. Both findings are indicative of a defect in the afferent limb of the upper airway dilator reflex that could prevent upper airway dilation secondary to airway loading, resulting in airway collapse. We hypothesized that children with OSA have impaired palate VT compared to controls, and that this improves after OSA treatment. METHODS: Case-control study. Children with OSA and healthy non-snoring controls underwent polysomnography and palate VT measurements. Children with OSA were retested after adenotonsillectomy. RESULTS: 29 children with OSA (median [interquartile range] age = 9.5 [7.5-12.6] years, obstructive apnea-hypopnea index [OAHI] = 11.3 [5.7 19.5] events/h, BMI z = 1.8 [1.3-2.1]) and 32 controls (age = 11.2 [9.3-13.5] years, P = 0.1; OAHI = 0.5 [0.1-0.7] events/h, P < 0.001; BMI z = 1 [0.3-1.7], P = 0.004) were tested. OSA palate VT (1.0 [0.8-1.5] vibration units) was similar to that of controls (1 [0.8-1.3], P = 0.37). 20 children with OSA were retested 4.4 (3.2-7.1) months after treatment. OAHI decreased from 13.1 (5.8-19) to 0.6 (0.2-2.5) events per hour (P < 0.001) postoperatively, but palate VT did not change (before = 1 [0.7-1.5], after = 1.2 [0.8-1.4], P = 0.37). CONCLUSIONS: Children with OSA and controls have similar palate VT. Unlike in adults, palate VT does not seem to be affected by childhood OSA. PMID- 27253765 TI - Familial Kleine-Levin Syndrome: A Specific Entity? AB - STUDY OBJECTIVES: Kleine-Levin syndrome (KLS) is a rare, mostly sporadic disorder, characterized by intermittent episodes of hypersomnia plus cognitive and behavior disorders. Although its cause is unknown, multiplex families have been described. We contrasted the clinical and biological features of familial versus sporadic KLS. METHODS: Two samples of patients with KLS from the United States and France (n = 260) were studied using clinical interviews and human leukocyte antigen (HLA) genotyping. A multiplex family contained two or more first- or second-degree affected relatives (familial cases). RESULTS: Twenty-one patients from 10 multiplex families (siblings: n = 12, including two pairs of monozygotic twins; parent-child: n = 4; cousins: n = 2; uncle-nephews: n = 3) and 239 patients with sporadic KLS were identified, yielding to 4% multiplex families and 8% familial cases. The simplex and multiplex families did not differ for autoimmune, neurological, and psychiatric disorders. Age, sex ratio, ethnicity, HLA typing, karyotyping, disease course, frequency, and duration of KLS episodes did not differ between groups. Episodes were less frequent in familial versus sporadic KLS (2.3 +/- 1.8/y versus 3.8 +/- 3.7/y, P = 0.004). Menses triggered more frequently KLS onset in the nine girls with familial KLS (relative risk, RR = 4.12, P = 0.03), but not subsequent episodes. Familial cases had less disinhibited speech (RR = 3.44, P = 0.049), less combined hypophagia/hyperphagia (RR = 4.38, P = 0.006), more abrupt termination of episodes (RR = 1.45, P = 0.04) and less postepisode insomnia (RR = 2.16, P = 0.008). There was similar HLA DQB1 distribution in familial versus sporadic cases and no abnormal karyotypes. CONCLUSION: Familial KLS is mostly present in the same generation, and is clinically similar to but slightly less severe than sporadic KLS. PMID- 27253766 TI - Cryptic Restlessness and Sleepwalking. PMID- 27253767 TI - The Social Patterning of Sleep in African Americans: Associations of Socioeconomic Position and Neighborhood Characteristics with Sleep in the Jackson Heart Study. AB - STUDY OBJECTIVES: We investigated cross-sectional associations of individual level socioeconomic position (SEP) and neighborhood characteristics (social cohesion, violence, problems, disadvantage) with sleep duration and sleep quality in 5,301 African Americans in the Jackson Heart Study. METHODS: All measures were self-reported. Sleep duration was assessed as hours of sleep; sleep quality was reported as poor (1) to excellent (5). SEP was measured by categorized years of education and income. Multinomial logistic and linear regression models were fit to examine the associations of SEP and neighborhood characteristics (modeled dichotomously and tertiles) with sleep duration (short vs. normal, long vs. normal) and continuous sleep duration and quality after adjustment for demographics and risk factors. RESULTS: The mean sleep duration was 6.4 +/- 1.5 hours, 54% had a short (<= 6 h) sleep duration, 5% reported long (>= 9 h) sleep duration, and 24% reported fair to poor sleep quality. Lower education was associated with greater odds of long sleep (odds ratio [OR] = 2.19, 95% confidence interval [CI] = 1.42, 3.38) and poorer sleep quality (beta = -0.17, 95% CI = -0.27, -0.07) compared to higher education after adjustment for demographics and risk factors. Findings were similar for income. High neighborhood violence was associated with shorter sleep duration (-9.82 minutes, 95% CI = -16.98, -2.66) and poorer sleep quality (beta = -0.11, 95% CI = -0.20, 0.00) after adjustment for demographics and risk factors. Results were similar for neighborhood problems. In secondary analyses adjusted for depressive symptoms in a subset of participants, most associations were attenuated and only associations of low SEP with higher odds of long sleep and higher neighborhood violence with poorer sleep quality remained statistically significant. CONCLUSIONS: Social and environmental characteristics are associated with sleep duration and quality in African Americans. Depressive symptoms may explain at least part of this association. PMID- 27253768 TI - Sleep Restriction Impairs Vocabulary Learning when Adolescents Cram for Exams: The Need for Sleep Study. AB - STUDY OBJECTIVES: The ability to recall facts is improved when learning takes place at spaced intervals, or when sleep follows shortly after learning. However, many students cram for exams and trade sleep for other activities. The aim of this study was to examine the interaction of study spacing and time in bed (TIB) for sleep on vocabulary learning in adolescents. METHODS: In the Need for Sleep Study, which used a parallel-group design, 56 adolescents aged 15-19 years were randomly assigned to a week of either 5 h or 9 h of TIB for sleep each night as part of a 14-day protocol conducted at a boarding school. During the sleep manipulation period, participants studied 40 Graduate Record Examination (GRE) type English words using digital flashcards. Word pairs were presented over 4 consecutive days (spaced items), or all at once during single study sessions (massed items), with total study time kept constant across conditions. Recall performance was examined 0 h, 24 h, and 120 h after all items were studied. RESULTS: For all retention intervals examined, recall of massed items was impaired by a greater amount in adolescents exposed to sleep restriction. In contrast, cued recall performance on spaced items was similar between sleep groups. CONCLUSIONS: Spaced learning conferred strong protection against the effects of sleep restriction on recall performance, whereas students who had insufficient sleep were more likely to forget items studied over short time intervals. These findings in adolescents demonstrate the importance of combining good study habits and good sleep habits to optimize learning outcomes. PMID- 27253769 TI - Automatic Video Analysis for Obstructive Sleep Apnea Diagnosis. AB - STUDY OBJECTIVES: We investigated the diagnostic accuracy for the identification of obstructive sleep apnea (OSA) and its severity of a noninvasive technology based on image processing (SleepWise). METHODS: This is an observational, prospective study to evaluate the degree of agreement between polysomnography (PSG) and SleepWise. We recruited 56 consecutive subjects with suspected OSA who were referred as outpatients to the Sleep Unit of the Hospital Universitari Germans Trias i Pujol (HUGTiP) from January 2013 to January 2014. All patients underwent laboratory PSG and image processing with SleepWise simultaneously the same night. Both PSG and SleepWise analyses were carried independently and blindly. RESULTS: We analyzed 50 of the 56 patients recruited. OSA was diagnosed through PSG in a total of 44 patients (88%) with a median apnea-hypopnea index (AHI) of 25.35 (24.9). According to SleepWise, 45 patients (90%) met the criteria for a diagnosis of OSA, with a median AHI of 22.8 (22.03). An analysis of the ability of PSG and SleepWise to classify patients by severity on the basis of their AHI shows that the two diagnostic systems distribute the different groups similarly. According to PSG, 23 patients (46%) had a diagnosis of severe OSA, 11 patients (22%) moderate OSA, and 10 patients (20%) mild OSA. According to SleepWise, 20, 13, and 12 patients (40%, 26%, and 24%, respectively) had a diagnosis of severe, moderate, and mild OSA respectively. For OSA diagnosis, SleepWise was found to have sensitivity of 100% and specificity of 83% in relation to PSG. The positive predictive value was 97% and the negative predictive value was 100%. The Bland-Altman plot comparing the mean AHI values obtained through PSG and SleepWise shows very good agreement between the two diagnostic techniques, with a bias of -3.85, a standard error of 12.18, and a confidence interval of -0.39 to -7.31. CONCLUSIONS: SleepWise was reasonably accurate for noninvasive and automatic diagnosis of OSA in outpatients. SleepWise determined the severity of OSA with high reliability. The current study including simultaneous laboratory PSG and SleepWise processing image is proposed as a reasonable validation standard. PMID- 27253770 TI - Exposure to Blue Light Increases Subsequent Functional Activation of the Prefrontal Cortex During Performance of a Working Memory Task. AB - STUDY OBJECTIVES: Prolonged exposure to blue wavelength light has been shown to have an alerting effect, and enhances performance on cognitive tasks. A small number of studies have also shown that relatively short exposure to blue light leads to changes in functional brain responses during the period of exposure. The extent to which blue light continues to affect brain functioning during a cognitively challenging task after cessation of longer periods of exposure (i.e., roughly 30 minutes or longer), however, has not been fully investigated. METHODS: A total of 35 healthy participants (18 female) were exposed to either blue (469 nm) (n = 17) or amber (578 nm) (n = 18) wavelength light for 30 minutes in a darkened room, followed immediately by functional magnetic resonance imaging (fMRI) while undergoing a working memory task (N-back task). RESULTS: Participants in the blue light condition were faster in their responses on the N back task and showed increased activation in the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex compared to those in the amber control light condition. Furthermore, greater activation within the VLPFC was correlated with faster N-back response times. CONCLUSIONS: This is the first study to suggest that a relatively brief, single exposure to blue light has a subsequent beneficial effect on working memory performance, even after cessation of exposure, and leads to temporarily persisting functional brain changes within prefrontal brain regions associated with executive functions. These findings may have broader implication for using blue-enriched light in a variety of work settings where alertness and quick decision-making are important. PMID- 27253771 TI - Erratum: Strain-Engineered Graphene Grown on Hexagonal Boron Nitride by Molecular Beam Epitaxy. PMID- 27253774 TI - Estimating Gait Stability: Asymmetrical Loading Effects Measured Using Margin of Stability and Local Dynamic Stability. AB - Changes to intersegmental locomotor control patterns may affect body stability. Our study aimed to (a) characterize upper body dynamic stability in response to the unilateral addition of mass to the lower extremity and (b) evaluate the efficacy of 2 different stability measures commonly used in the literature to detect resulting symmetrical step pattern modifications across the weighted segments (spatial) and between epochs of the gait cycle (temporal). Young adults walked on a treadmill while unloaded or with weights applied unilaterally to their foot, shank, or thigh. Both margin of stability and local dynamic stability (LDS) estimates detected similar trends of distal segment weighting resulting in more unstable upper body movement compared to proximal weighting; however only LDS detected anteroposterior changes in upper body stability over time. PMID- 27253772 TI - Pharmacogenetics and interstitial lung disease. AB - PURPOSE OF REVIEW: Interstitial lung disease (ILD) is comprised of a heterogeneous group of disorders with highly variable natural histories and response to therapies. Pharmacogenetics focuses on the variability in drug response because of the presence of genetic factors that influence drug metabolism or disease activity. In this article, we review relevant drug-specific and disease-specific polymorphisms that may influence therapeutic response, and then highlight a recently identified drug-gene interaction in patients with idiopathic pulmonary fibrosis (IPF). RECENT FINDINGS: The emergence of high throughput genomic technology has allowed for identification of gene polymorphisms associated with susceptibility to specific disease states, including IPF and several connective tissue diseases known to cause ILD. IPF risk loci span a diverse group of genes, while most associated with connective tissue disease are critical to immune signaling. A recent pharmacogenetic analysis of patients enrolled in an IPF clinical trial identified a variant within TOLLIP to be associated with differential response to N-acetylcysteine therapy. SUMMARY: Though few pharmacogenetic investigations have been conducted in patients with ILD to date, ample opportunities for pharmacogenetic exploration exist in this patient population. Such exploration will advance our understanding of specific ILDs and help usher in an era of personalized medicine. PMID- 27253773 TI - QSAR-Driven Discovery of Novel Chemical Scaffolds Active against Schistosoma mansoni. AB - Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro 1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol 3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents. PMID- 27253817 TI - Central Corneal Thickness in Aphakic Children With Microcornea-Microphthalmia. AB - PURPOSE: To study the central corneal thickness (CCT) in eyes with microcornea and aphakia and without glaucoma, compare it with normal controls, and correlate it with the measured intraocular pressure (IOP). METHODS: The study was conducted on 62 eyes of 31 aphakic children with microcornea. Controls (20 children) were selected from age-matched children presenting for routine refraction. Detailed anterior-segment and fundus examinations were conducted. The CCT and the axial length were measured. Medical records of the study patients were reviewed for the stability of the ocular parameters over time to exclude glaucoma. RESULTS: The mean+/-SD age of the study patients and controls were 4.0 (+/-3.1, 1.0 to 12.0) and 3.1 (+/-2.7, 0.6 to 12.0) years, respectively. The mean+/-SD CCT, the corneal diameter, the measured IOP, the cup/disc ratio, and the axial length of the study patients and the controls were 667.01+/-72.90 MUm, 8.9+/-0.8 mm, 10.9+/-5.7 mm Hg, 0.1+/-0.1, 20.35+/-2.90 mm and 545.22+/-28.14 MUm, 11.7+/-0.5 mm, 5.3+/-1.8 mm Hg, 0.1+/-0.1, and N/A, respectively. The difference between the study eyes and the controls in the CCT and the measured IOP was statistically significant (P<0.05). CONCLUSIONS: Aphakic eyes with microcornea have thicker CCTs and greater measured IOPs than normal eyes. Hence, the measurement of CCT is recommended in the assessment of aphakic eyes with microcornea for possible glaucoma. The measured IOP, although a reliable parameter, in isolation does not provide a diagnosis of glaucoma and must be viewed in conjunction with other patient findings, such as the cup/disc ratio, the progression of which over time must be considered for a more solid diagnosis. PMID- 27253829 TI - CYP2D6 function moderates the pharmacokinetics and pharmacodynamics of 3,4 methylene-dioxymethamphetamine in a controlled study in healthy individuals. AB - The role of genetic polymorphisms in cytochrome (CYP) 2D6 involved in the metabolism of 3,4-methylene-dioxymethamphetamine (MDMA, ecstasy) is unclear. Effects of genetic variants in CYP2D6 on the pharmacokinetics and pharmacodynamic effects of MDMA were characterized in 139 healthy individuals (70 men, 69 women) in a pooled analysis of eight double-blind, placebo-controlled crossover studies. In CYP2D6 poor metabolizers, the maximum concentrations (Cmax) of MDMA and its active metabolite 3,4-methylene-dioxyamphetamine were +15 and +50% higher, respectively, compared with extensive metabolizers and the Cmax of the inactive metabolite 4-hydroxy-3-methoxymethamphetamine was 50-70% lower. Blood pressure and subjective drug effects increased more rapidly after MDMA administration in poor metabolizers than in extensive metabolizers. In conclusion, the disposition of MDMA and its effects in humans are altered by polymorphic CYP2D6 activity, but the effects are small because of the autoinhibition of CYP2D6. PMID- 27253830 TI - Design, synthesis, molecular modeling and biological evaluation of novel 1H pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents. AB - In trying to develop new anticancer agents, a series of 1H-pyrazolo[3,4 b]pyridine derivatives was designed and synthesized. Fifteen compounds were evaluated in vitro for their anti-proliferative activity against HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Additionally, DNA binding affinity of the synthesized derivatives was investigated as a potential mechanism for the anticancer activity using DNA/methyl green assay and association constants assay. Compounds 19, 20, 21, 24 and 25 exhibited good activity against the four cancer cells comparable to that of doxorubicin. Interestingly, DNA binding assay results were in agreement with that of the cytotoxicity assays where the most potent anticancer compounds showed good DNA binding affinity comparable to that of doxorubicin and daunorubicin. Furthermore, a molecular docking of the tested compounds was carried out to investigate their binding pattern with the prospective target, DNA (PDB-code: 152d). PMID- 27253831 TI - The Prevalence of Exfoliation Syndrome in an Iranian Population Aged 45-69 Years. AB - PURPOSE: To determine the prevalence of exfoliation syndrome (XFS) and some of its related factors in an Iranian population aged 45-69 years. METHODS: In the first phase of the Shahroud Eye Cohort Study, 5190 people in 300 clusters from Shahroud city in the northeast of Iran participated in the study. The second phase of the study was conducted 5 years later in 2014. Vision testing, refraction, slit lamp examination, and fundus examination were performed for all participants. In this study, XFS was determined by an ophthalmologist using slit lamp biomicroscopy. RESULTS: Of the 5190 first phase study participants, 4737 participated in the second phase (response rate 91.3%). In this study, the prevalence of XFS was 0.46% (95% confidence interval, CI, 0.24-0.68%) and the prevalence of bilateral XFS was 0.20% (95% CI 0.07-0.33%). XFS prevalence in men was 0.74% (95% CI 0.28-1.20%) and in women 0.26% (95% CI 0.07-0.45%). In a multivariable-adjusted logistic regression model, age, sex, diabetes, smoking status, dyslipidemia, and hypertension were entered into the model as covariables, where older age (odds ratio, OR, 1.18, 95% CI 1.08-1.28) was the only variable that remained significantly associated with XFS prevalence. CONCLUSION: The prevalence of XFS in this study was very low. Similar to other studies, age was a factor associated with this syndrome. PMID- 27253832 TI - Maximal Strength Training Improves Surfboard Sprint and Endurance Paddling Performance in Competitive and Recreational Surfers. AB - Coyne, JOC, Tran, TT, Secomb, JL, Lundgren, LE, Farley, ORL, Newton, RU, and Sheppard, JM. Maximal strength training improves surfboard sprint and endurance paddling performance in competitive and recreational surfers. J Strength Cond Res 31(1): 244-253, 2017-Upper-body (UB) strength has very high correlations with faster surfboard paddling speeds. However, there is no research examining the effects of improving UB strength has on surfboard paddling ability. This study aimed to determine the influence that improvements in UB closed-kinetic chain maximal strength have on surfboard paddling in both competitive and recreational surfers. Seventeen competitive and recreational male surfers (29.7 +/- 7.7 years, 177.4 +/- 7.4 cm, 76.7 +/- 9.9 kg) participated in a repeated-measures, parallel control study design. Anthropometry; 5-, 10-, and 15-m sprint; and 400-m endurance surfboard paddling tests along with pull-up and dip 1 repetition maximum strength tests were assessed pre- and postintervention. Subjects in the training group performed 5 weeks of maximal strength training in the pull-up and dip. Differences between the training and control groups were examined postintervention. The training group increased their speed over the 5-, 10-, and 15-m sprint, whereas the control group became slower (d = 0.71, 0.51, and 0.4, respectively). The training group also displayed faster endurance paddling performance compared with the control group (d = 0.72). Short-term exposure to maximal strength training elicits improvements in paddling performance measures. However, the magnitude of performance increases seems to be dependent on initial strength levels with differential responses between strong and weaker athletes. Although a longer maximal strength training period may have produced more significant paddling improvements in stronger subjects, practitioners are unlikely to have any more than 5 weeks in an uninterrupted block with competitive surfing athletes. This study reveals that a "threshold" level of maximal strength that if possessed, short-term maximal strength training may only provide little improvement in paddling performance. PMID- 27253833 TI - Manuscript Clarification. PMID- 27253835 TI - Effects of a Six-Week Hip Thrust vs. Front Squat Resistance Training Program on Performance in Adolescent Males: A Randomized Controlled Trial. AB - Contreras, B, Vigotsky, AD, Schoenfeld, BJ, Beardsley, C, McMaster, DT, Reyneke, JHT, and Cronin, JB. Effects of a six-week hip thrust vs. front squat resistance training program on performance in adolescent males: A randomized controlled trial. J Strength Cond Res 31(4): 999-1008, 2017-The barbell hip thrust may be an effective exercise for increasing horizontal force production and may thereby enhance performance in athletic movements requiring a horizontal force vector, such as horizontal jumping and sprint running. The ergogenic ability of the squat is well known. The purpose of this study was to compare the effects of 6-week front squat and hip thrust programs in adolescent male athletes. Vertical jump height, horizontal jump distance, 10- and 20-m sprint times, and isometric midthigh pull peak force were among the measured performance variables, in addition to front squat and hip thrust 3 repetition maximum (3RM) strength. Magnitude-based effect sizes revealed potentially beneficial effects for the front squat in both front squat 3RM strength and vertical jump height when compared with the hip thrust. No clear benefit for one intervention was observed for horizontal jump performance. Potentially beneficial effects were observed for the hip thrust compared with the front squat in 10- and 20-m sprint times. The hip thrust was likely superior for improving normalized isometric midthigh pull strength and very likely superior for improving hip thrust 3RM and isometric midthigh pull strength. These results support the force vector theory. PMID- 27253836 TI - Influence of Strength Level on the Rest Interval Required During an Upper-Body Power Training Session. AB - Hernandez Davo, JL, Botella Ruiz, J, and Sabido, R. Influence of strength level on the rest interval required during an upper-body power training session. J Strength Cond Res 31(2): 339-347, 2017-The present study aimed to investigate the influence of subjects' strength level on both the ability to maintain power output performance and the physiological and perceived exertion responses during a power training session when different rest intervals (RI) are used. Thirty eight (18 men and 20 women) subjects were divided into a stronger or weaker group based on their ability to produce peak power output. Testing was performed using the same protocol (5 sets of 8 repetitions with 40% of 1 repetition maximum) in the bench press throw exercise, but differing the RI between sets (1, 2, and 3 minutes). During the sessions, mechanical (peak power), physiological ([La]) and perceptual (RPE) variables were measured. In addition, delayed onset muscular soreness (DOMS) 24 and 48 hours after the training session was reported. Both stronger and weaker (men and women) groups showed significant impairments in mechanical, physiological, and perceptual data when resting 1 minute. Nevertheless, although stronger groups were able to sustain power output over the sets when using the 2-minute RI, weaker groups needed at least 3 minutes to maintain power output performance. Therefore, strength level heavily influences the rest interval required during a power training session and should be taken into account when prescribing such training sessions. PMID- 27253837 TI - Arterial Stiffness and Autonomic Modulation After Free-Weight Resistance Exercises in Resistance Trained Individuals. AB - Kingsley, JD, Mayo, X, Tai, YL, and Fennell, C. Arterial stiffness and autonomic modulation after free-weight resistance exercises in resistance trained individuals. J Strength Cond Res 30(12): 3373-3380, 2016-We investigated the effects of an acute bout of free-weight, whole-body resistance exercise consisting of the squat, bench press, and deadlift on arterial stiffness and cardiac autonomic modulation in 16 (aged 23 +/- 3 years; mean +/- SD) resistance trained individuals. Arterial stiffness, autonomic modulation, and baroreflex sensitivity (BRS) were assessed at rest and after 3 sets of 10 repetitions at 75% 1-repetition maximum on each exercise with 2 minutes of rest between sets and exercises. Arterial stiffness was analyzed using carotid-femoral pulse wave velocity (cf-PWV). Linear heart rate variability (log transformed [ln] absolute and normalized units [nu] of low-frequency [LF] and high-frequency [HF] power) and nonlinear heart rate complexity (Sample Entropy [SampEn], Lempel-Ziv Entropy [LZEn]) were measured to determine autonomic modulation. BRS was measured by the sequence method. A 2 * 2 repeated measures analysis of variance (ANOVA) was used to analyze time (rest, recovery) across condition (acute resistance exercise, control). There were significant increases in cf-PWV (p = 0.05), heart rate (p = 0.0001), normalized LF (LFnu; p = 0.001), and the LF/HF ratio (p = 0.0001). Interactions were also noted for ln HF (p = 0.006), HFnu (p = 0.0001), SampEn (p = 0.001), LZEn (p = 0.005), and BRS (p = 0.0001) such that they significantly decreased during recovery from the resistance exercise compared with rest and the control. There was no effect on ln total power, or ln LF. These data suggest that a bout of resistance exercise using free-weights increases arterial stiffness and reduces vagal activity and BRS in comparison with a control session. Vagal tone may not be fully recovered up to 30 minutes after a resistance exercise bout. PMID- 27253838 TI - Impact of Prescribed Exercise on Physical Activity Compensation in Young Adults. AB - Liguori, G, Schuna, JM Jr, Tucker, J, and Fountaine, CM. Impact of prescribed exercise on physical activity compensation in young adults. J Strength Cond Res 31(2): 503-508, 2017-Army Reserve Officers' Training Corps cadets present a unique subpopulation because they are required to participate in regular physical activity (PA). This study describes PA patterns of cadets and attempts to identify evidence of nonexercise PA compensation (activitystat) as a result of prescribed PA (pPA) by comparing differences between training and nontraining days for (a) autonomous PA among cadets and (b) PA between cadets and noncadets. Participants included 84 university students (33 cadets and 51 noncadets) who each wore an accelerometer for 5 consecutive days to estimate moderate and vigorous physical activity (MVPA). A 2*2 mixed model analysis of variance was used to examine within- and between-group differences in MVPA on training and nontraining days. This analysis was repeated after removing the cadet's pPA. Cadets had lower-body fat than noncadets (p = 0.044), but all other characteristics were similar. Overall, moderate PA (MPA) and vigorous PA (VPA) were significantly greater among cadets (p = 0.048 and p < 0.001), because of greater weekend MPA (p = 0.021) and greater weekday VPA (p < 0.001). Cadets accumulated more MVPA on training days than nontraining days (p < 0.001) and accumulated more MVPA than noncadets on training days (p = 0.004). However, after accounting for pPA, cadet MVPA did not differ between training and nontraining days (within 1.2A +/- 18.4 min.d) and was similar between cadets and noncadets (within 1.5A +/- 5.9 min.d). These results suggest that cadets were significantly more active than noncadets due mainly to pPA. When controlling for pPA, cadets were similarly active across all days, and were as active as noncadets, indicating no evidence of activitystat in this population. PMID- 27253839 TI - Combined Experimental and Theoretical Investigations on Optical Activities of Mobius Aromatic and Mobius Antiaromatic Hexaphyrin Phosphorus Complexes. AB - Intrinsically chiral Mobius aromatic [28]hexaphyrin monophosphorus(V) and Mobius antiaromatic [30]hexaphyrin bisphosphorus(V) complexes have been optically resolved and their absolute configurations (ACs) were determined by combined experimental and theoretical investigations on their circular dichroisms (CDs). First elutes in chiral HPLC exhibited strong positive Cotton effects (CEs) at the B-band, characteristic for the ML configurations in their Mobius strips. Weak CEs at the Q-band, if attainable, complemented their AC assignment. The whole CD pattern and intensity were well reproduced by time-dependent approximate coupled cluster theory using model systems that omit five outward meso-aryl substituents (inward-meso-retained model), providing a solid basis for AC assignment. The cost efficient TD-DFT method with appropriate functionals for fully substituted (nontruncated) complexes well reproduced CEs around the B-band (but less satisfactory at the Q-band), also allows the rapid AC estimation for their Mobius strips. Observed difference in CDs between aromatic and antiaromatic hexaphyrins were better interpreted by their shifts in energy levels and altered interactions of relevant molecular orbitals, rather than small differences in Mobius geometries nor aromatic/antiaromatic character, despite the correlations recently claimed in planar pi-systems. PMID- 27253840 TI - Effects of Combat and Military Training on End-of-Life Care. PMID- 27253841 TI - Intravenous lipid emulsions in the critically ill: an update. AB - PURPOSE OF REVIEW: Purpose of the review is to summarize recent research addressing the role of intravenous lipid emulsions (IVLEs) in the critically ill. RECENT FINDINGS: Soybean oil-based IVLEs, which are high in the omega-6 polyunsaturated fatty acids, have been largely used in parenteral nutrition over the last several decades. However, it is now generally accepted that the higher content of phytosterols and polyunsaturated fatty acids in soybean oil IVLE may adversely affect the immunological and inflammatory status of the critically ill. In the last few years, alternative IVLEs with lower soybean oil content have been associated with important improvements in clinical outcomes, such as mortality, mechanical ventilation days, and ICU length of stay. Olive oil and fish oil IVLEs have been reported to reduce the incidence of infections, with no clear benefits in other clinical outcomes. Despite the promising results with these new parenteral nutrition strategies, the optimum composition, dosage and indication for alternative IVLEs still remain controversial. Nevertheless, according to current knowledge alternative IVLEs may be associated with improved clinical outcomes and should be considered in critically ill patients requiring parenteral nutrition. SUMMARY: There is a growing body of evidence suggesting that improved clinical outcomes can be achieved with selective use of alternative IVLEs in parenteral nutrition regimens for the critically ill. More high quality trials are needed, to better evaluate the efficacy of alternative IVLEs. PMID- 27253842 TI - Postoperative bleeding and coagulation disorders. AB - PURPOSE OF REVIEW: New data have been made available in the field of haemostasis and thrombosis. Some long-awaited answers to important questions have been published, and some debates have benefited from an updated perspective. RECENT FINDINGS: Two important domains are addressed in this update: massive bleeding (1/1/1 ratios and fibrinogen concentrates) and the management of direct oral anticoagulants (monitoring and antidotes). Both are highly controversial topics. Higher plasma/platelets/red blood cells units ratios are now partly supported by a new study in trauma. Several studies show that preemptive doses of fibrinogen do not appear to bring any benefit. Monitoring of direct oral anticoagulants is now possible, and it has to be recommended in some circumstances. Specific antidotes are being developed, but there are still more questions than answers. SUMMARY: These new data should help anaesthesiologists and intensivists to better understand and manage massively bleeding patients or direct oral anticoagulants treated patients. PMID- 27253843 TI - Postoperative hemodynamic instability and monitoring. AB - PURPOSE OF REVIEW: The purpose of the review is to identify the recently validated minimally invasive or noninvasive monitoring devices used to both monitor and guide resuscitation in the critically ill patients. RECENT FINDINGS: Recent advances in noninvasive measures of blood pressure, blood flow, and vascular tone have been validated and complement existing minimally invasive and invasive monitoring techniques. These monitoring approaches should be used within the context of a focused physical examination and static vital sign analysis. When available, measurement of urinary output is often included. All studies show that minimally invasive and noninvasive measure of arterial pressure and cardiac output are possible and often remain as accurate as invasive measures. The noninvasive techniques degrade in severe circulatory failure and the use of vasopressor therapy. Importantly, these output parameters form the treatment goals for many goal-directed therapies protocols. SUMMARY: When coupled with a focused physical examination and functional hemodynamic monitoring analyses, these measures become even more specific at defining volume responsiveness and vasomotor tone and can be used to drive resuscitation strategies. PMID- 27253844 TI - Oldies but goodies: The Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS) data can be used with the data obtained before the year 2012. PMID- 27253845 TI - Monothiocarbamates Strongly Inhibit Carbonic Anhydrases in Vitro and Possess Intraocular Pressure Lowering Activity in an Animal Model of Glaucoma. AB - A series of monothiocarbamates (MTCs) were prepared from primary/secondary amines and COS as potential carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, using the dithiocarbamates, the xanthates, and the trithiocarbonates as lead compounds. The MTCs effectively inhibited the pharmacologically relevant human (h) hCAs isoforms I, II, IX, and XII in vitro and showed KIs spanning between the low and medium nanomolar range. By means of a computational study, the MTC moiety binding mode on the CAs was explained. Furthermore, a selection of MTCs were evaluated in a normotensive glaucoma rabbit model for their intraocular pressure (IOP) lowering effects and showed interesting activity. PMID- 27253846 TI - Satisficing in split-second decision making is characterized by strategic cue discounting. AB - Much of our real-life decision making is bounded by uncertain information, limitations in cognitive resources, and a lack of time to allocate to the decision process. It is thought that humans overcome these limitations through satisficing, fast but "good-enough" heuristic decision making that prioritizes some sources of information (cues) while ignoring others. However, the decision making strategies we adopt under uncertainty and time pressure, for example during emergencies that demand split-second choices, are presently unknown. To characterize these decision strategies quantitatively, the present study examined how people solve a novel multicue probabilistic classification task under varying time pressure, by tracking shifts in decision strategies using variational Bayesian inference. We found that under low time pressure, participants correctly weighted and integrated all available cues to arrive at near-optimal decisions. With increasingly demanding, subsecond time pressures, however, participants systematically discounted a subset of the cue information by dropping the least informative cue(s) from their decision making process. Thus, the human cognitive apparatus copes with uncertainty and severe time pressure by adopting a "drop-the worst" cue decision making strategy that minimizes cognitive time and effort investment while preserving the consideration of the most diagnostic cue information, thus maintaining "good-enough" accuracy. This advance in our understanding of satisficing strategies could form the basis of predicting human choices in high time pressure scenarios. (PsycINFO Database Record PMID- 27253848 TI - Is formamide a geochemically plausible prebiotic solvent? AB - From a geochemical perspective, significant amounts of pure formamide (HCONH2) would have likely been rare on the early Earth. There may have been mixed formamide-water solutions, but even in the presence of catalyst, solutions with >20 weight% water in formamide would not have produced significant amounts of prebiotic compounds. It might be feasible to produce relatively pure formamide by a rare occurrence of freezing formamide/water mixtures at temperatures lower than formamide's freezing point (2.55 degrees C) but greater than the freezing point of water. Because of the high density of formamide ice it would have sunk and accumulated at the bottom of the solution. If the remaining water froze on the surface of this ice, and was then removed by a sublimation-ablation process, a small amount of pure formamide ice might have been produced. In addition a recent report suggested that ~85 weight% formamide could be prepared by a geochemical type of fractional distillation process, offering another possible route for prebiotic formamide production. PMID- 27253847 TI - The LysR-type transcriptional regulator, CidR, regulates stationary phase cell death in Staphylococcus aureus. AB - The Staphylococcus aureus LysR-type transcriptional regulator, CidR, activates the expression of two operons including cidABC and alsSD that display pro- and anti-death functions, respectively. Although several investigations have focused on the functions of different genes associated with these operons, the collective role of the CidR regulon in staphylococcal physiology is not clearly understood. Here we reveal that the primary role of this regulon is to limit acetate dependent potentiation of cell death in staphylococcal populations. Although both CidB and CidC promote acetate generation and cell death, the CidR-dependent co activation of CidA and AlsSD counters the effects of CidBC by redirecting intracellular carbon flux towards acetoin formation. From a mechanistic standpoint, we demonstrate that CidB is necessary for full activation of CidC, whereas CidA limits the abundance of CidC in the cell. PMID- 27253849 TI - Biology and management of clear cell sarcoma: state of the art and future perspectives. AB - INTRODUCTION: Clear cell sarcoma (CCS) is an aggressive tumor, typically developing in tendons or aponeuroses. The outcome of this orphan disease is poor, with 5-year and 10-year survival rates of localized CCS around 60-70% and 40-50%. Once the disease has metastasized, it is usually fatal due to its chemotherapy resistant nature. Systemic treatment options are poorly standardized and the use of chemotherapy is based on weak scientific evidence. AREAS COVERED: In this review, we systematically discuss the current scientific evidence for the systemic treatment of CCS, including tyrosine kinase inhibitors, immunotherapy and MET inhibitors. Expert commentary: Recent insights in the biology of CCS have identified new potential therapeutic targets, which should be tested in prospective clinical trials. Whenever possible, patients with metastatic CCS should be included in clinical trials with good biological rationale. Innovative trial methodology and new regulatory mechanisms are required to provide patients with uncommon cancers with active drugs. PMID- 27253850 TI - Lower critical solution temperature (LCST) phase behaviour of an ionic liquid and its control by supramolecular host-guest interactions. AB - Lower critical solution temperature (LCST) phase behaviour of an imidazolium based ionic liquid is reported, which can be controlled by concentration, the choice of cation, anion and solvent, and by supramolecular host-guest complex formation. Molecular dynamics simulations provide insight into the molecular basis of this LCST phenomenon. This thermo-responsive system has potential applications in cloud point extraction processes. PMID- 27253862 TI - Pupil dilation during recognition memory: Isolating unexpected recognition from judgment uncertainty. AB - Optimally discriminating familiar from novel stimuli demands a decision-making process informed by prior expectations. Here we demonstrate that pupillary dilation (PD) responses during recognition memory decisions are modulated by expectations, and more specifically, that pupil dilation increases for unexpected compared to expected recognition. Furthermore, multi-level modeling demonstrated that the time course of the dilation during each individual trial contains separable early and late dilation components, with the early amplitude capturing unexpected recognition, and the later trailing slope reflecting general judgment uncertainty or effort. This is the first demonstration that the early dilation response during recognition is dependent upon observer expectations and that separate recognition expectation and judgment uncertainty components are present in the dilation time course of every trial. The findings provide novel insights into adaptive memory-linked orienting mechanisms as well as the general cognitive underpinnings of the pupillary index of autonomic nervous system activity. PMID- 27253863 TI - Object formation in visual working memory: Evidence from object-based attention. AB - We report on how visual working memory (VWM) forms intact perceptual representations of visual objects using sub-object elements. Specifically, when objects were divided into fragments and sequentially encoded into VWM, the fragments were involuntarily integrated into objects in VWM, as evidenced by the occurrence of both positive and negative object-based attention effects: In Experiment 1, when subjects' attention was cued to a location occupied by the VWM object, the target presented at the location of that object was perceived as occurring earlier than that presented at the location of a different object. In Experiment 2, responses to a target were significantly slower when a distractor was presented at the same location as the cued object (Experiment 2). These results suggest that object fragments can be integrated into objects within VWM in a manner similar to that of visual perception. PMID- 27253864 TI - The implications of genetic variation for the pharmacokinetics and pharmacodynamics of aromatase inhibitors. AB - INTRODUCTION: Breast cancer is the most common female cancer and remains a serious public health concern worldwide. Third-generation aromatase inhibitors (AIs) are widely used in postmenopausal women with estrogen receptor positive breast cancer. However, there is marked interindividual variability in terms of the efficacy and incidence of adverse events following treatment with AIs. Pharmacogenetics has the potential to predict clinical outcomes based on patients' genetic information, paving the way towards personalized treatment. AREAS COVERED: This article reviews pharmacogenetic studies of AIs, including pharmacokinetic and pharmacodynamic aspects, highlighting those studies where the efficacy and adverse events of AIs have been examined using both candidate gene and genome-wide approaches. EXPERT OPINION: Pharmacogenetics is a promising approach to develop personalized medicine with AIs. However, the application of pharmacogenetics to predict therapeutic efficacy and adverse events in breast cancer patients is still far from implementation in routine clinical practice. Large, comprehensive, multicenter studies that simultaneously evaluate multiple genes and pathways, including rare variants, are warranted in order to produce reliable and informative results. The ultimate aim is to develop clinically relevant guidelines for breast cancer therapy. PMID- 27253865 TI - Effect of Ionic Liquids on Zebrafish (Danio rerio) Viability, Behavior, and Histology; Correlation between Toxicity and Ionic Liquid Aggregation. AB - The effect of 11 common amidinium, imidazolium, and phosphonium based ionic liquids (ILs) on zebrafish (Danio rerio) and Chinese hamster ovary cells (CHO) was investigated with specific emphasis on the effect of anion and cation chain length and aggregation of phosphonium based ILs. Viability and behavioral alteration in the locomotor activity and place preference, after IL treatment of 5 days postfertilization larvae, was recorded. Behavior and histological damage evaluation was performed for adult fish in order to get insight into the long term effects of two potential biomass-dissolving ILs, [DBNH][OAc] and [P4441][OAc]. To get an understanding of how IL aggregation is linked to the toxicity of ILs, median effective concentrations (EC50) and critical micelle concentrations (CMC) were determined. The long-chain ILs were significantly more toxic than the short-chain ones, and the anion chain length was shown to be less significant than the cation chain length when assessing the impact of ILs on the viability of the organisms. Furthermore, most of the ILs were as monomers when the EC50 was reached. In addition, the ILs used in the long-term tests showed no significant effect on the zebrafish behavior, breeding, or histology, within the used concentration range. PMID- 27253866 TI - Childhood cancer survivorship research in minority populations: A position paper from the Childhood Cancer Survivor Study. AB - By the middle of this century, racial/ethnic minority populations will collectively constitute 50% of the US population. This temporal shift in the racial/ethnic composition of the US population demands a close look at the race/ethnicity-specific burden of morbidity and premature mortality among survivors of childhood cancer. To optimize targeted long-term follow-up care, it is essential to understand whether the burden of morbidity borne by survivors of childhood cancer differs by race/ethnicity. This is challenging because the number of minority participants is often limited in current childhood cancer survivorship research, resulting in a paucity of race/ethnicity-specific recommendations and/or interventions. Although the overall childhood cancer incidence increased between 1973 and 2003, the mortality rate declined; however, these changes did not differ appreciably by race/ethnicity. The authors speculated that any racial/ethnic differences in outcome are likely to be multifactorial, and drew on data from the Childhood Cancer Survivor Study to illustrate the various contributors (socioeconomic characteristics, health behaviors, and comorbidities) that could explain any observed differences in key treatment-related complications. Finally, the authors outlined challenges in conducting race/ethnicity-specific childhood cancer survivorship research, demonstrating that there are limited absolute numbers of children who are diagnosed and survive cancer in any one racial/ethnic minority population, thereby precluding a rigorous evaluation of adverse events among specific primary cancer diagnoses and treatment exposure groups. Cancer 2016;122:2426-2439. (c) 2016 American Cancer Society. PMID- 27253868 TI - No age deficits in the ability to use attention to improve visual working memory. AB - Maintenance of information in mind to the moment-to-moment cognition is accomplished by working memory (WM). WM capacity is reduced in old age, but the nature of this decline is yet not clear. The current study examined the hypothesis that the decline in visual WM performance with age is related to a reduced ability to use attention to control the contents of WM. Young (M = 26 years) and old (M = 71 years) adults performed a color reproduction task in which the precise color of a set of dots had to be maintained in mind over a brief interval and later reproduced using a continuous color wheel. Attention was manipulated by presenting a spatial cue before the onset of the memory array (a precue) or during the maintenance phase (retro-cue). The cue indicated with 100% certainty the item to be tested at the end of the trial. A precue allows the selective encoding of only the relevant item to WM, whereas a retro-cue allows WM contents to be updated by refreshing the relevant (cued) item and removing nonrelevant (noncued) items. Aging was associated with a lower capacity in the baseline (no-cue) condition. Precues and (to a smaller extent) retro-cues improved WM performance (in terms of probability of recall and memory precision). Critically, the benefits of cueing were of similar magnitude in young and older adults showing that the ability to use attention to selectively encode and update the contents of WM is preserved with aging. (PsycINFO Database Record PMID- 27253867 TI - Early selection versus late correction: Age-related differences in controlling working memory contents. AB - We examined whether a reduced ability to ignore irrelevant information is responsible for the age-related decline of working memory (WM) functions. By means of event-related brain potentials, we will show that filtering is not out of service in older adults but shifted to a later processing stage. Participants performed a visual short-term memory task (change-detection task) in which targets were presented along with distractors. To allow early selection, a cue was presented in advance of each display, indicating where the targets were to appear. Despite this relatively easy selection criterion, older adults' filtering was delayed as indicated by the amplitude pattern of the contralateral delay activity. Importantly, WM-equated younger adults did not show a delay indicating that the delay is specific to older adults and not a general phenomenon that comes with low WM capacity. Moreover, the analysis of early visual potentials revealed qualitatively different perceptual/attentional processing between the age groups. Young adults exhibited stronger distractor sensitivity that in turn facilitated filtering. Older adults, in contrast, seemed to initially store distractors and to suppress them after the fact. These early selection versus late-correction modes suggest an age-related shift in the strategy to control the contents of WM. (PsycINFO Database Record PMID- 27253869 TI - Crowdsourcing Vector Surveillance: Using Community Knowledge and Experiences to Predict Densities and Distribution of Outdoor-Biting Mosquitoes in Rural Tanzania. AB - Lack of reliable techniques for large-scale monitoring of disease-transmitting mosquitoes is a major public health challenge, especially where advanced geo information systems are not regularly applicable. We tested an innovative crowd sourcing approach, which relies simply on knowledge and experiences of residents to rapidly predict areas where disease-transmitting mosquitoes are most abundant. Guided by community-based resource persons, we mapped boundaries and major physical features in three rural Tanzanian villages. We then selected 60 community members, taught them basic map-reading skills, and offered them gridded maps of their own villages (grid size: 200m*200m) so they could identify locations where they believed mosquitoes were most abundant, by ranking the grids from one (highest density) to five (lowest density). The ranks were interpolated in ArcGIS-10 (ESRI-USA) using inverse distance weighting (IDW) method, and re classified to depict areas people believed had high, medium and low mosquito densities. Finally, we used odor-baited mosquito traps to compare and verify actual outdoor mosquito densities in the same areas. We repeated this process for 12 months, each time with a different group of 60 residents. All entomological surveys depicted similar geographical stratification of mosquito densities in areas classified by community members as having high, medium and low vector abundance. These similarities were observed when all mosquito species were combined, and also when only malaria vectors were considered. Of the 12,412 mosquitoes caught, 60.9% (7,555) were from areas considered by community members as having high mosquito densities, 28% (3,470) from medium density areas, and 11.2% (1,387) from low density areas. This study provides evidence that we can rely on community knowledge and experiences to identify areas where mosquitoes are most abundant or least abundant, even without entomological surveys. This crowd-sourcing method could be further refined and validated to improve community based planning of mosquito control operations at low-cost. PMID- 27253870 TI - A Polymorphism in RNF213 Is a Susceptibility Gene for Intracranial Atherosclerosis. AB - BACKGROUND: Both intracranial atherosclerotic stenosis (ICAS) and moyamoya disease (MMD) are prevalent in Asians. We hypothesized that the Ring Finger protein 213 gene polymorphism (RNF213), a susceptibility locus for MMD in East Asians, is also a susceptibility gene for ICAS in patients whose diagnosis had been confirmed by conventional angiography (absence of basal collaterals) and high-resolution MRI (HR-MRI, presence of plaque). METHODS: We analyzed 532 consecutive patients with ischemic events in the middle cerebral artery (MCA) distribution and relevant stenotic lesion on the distal internal carotid artery or proximal MCA, but no demonstrable carotid or cardiac embolism sources. Additional angiography was performed on 370 (69.5%) patients and HR-MRI on 283 (53.2%) patients. RESULTS: Based on angiographic and HR-MRI findings, 234 patients were diagnosed with ICAS and 288 with MMD. The RNF213 variant was observed in 50 (21.4%) ICAS patients and in 119 (69.1%) MMD patients. The variant was observed in 25.2% of patients with HR-MRI-confirmed ICAS. Similarly, 15.8% of ICAS patients in whom MMD was excluded by angiography had this variant. Among the ICAS patients, RNF213 variant carriers were younger and more likely to have a family history of MMD than non-carriers were. Multivariate testing showed that only the age of ICAS onset was independently associated with the RNF213 variant (odds ratio, 0.97; 95% CI, 0.944-0.99). CONCLUSIONS: RNF213 is a susceptibility gene not only for MMD but also for ICAS in East Asians. Further studies are needed on RNF213 variants in ICAS patients outside East Asian populations. PMID- 27253871 TI - Surveying the new Allergic and hypersensitivity conditions chapter of the International Classification of Diseases (ICD)-11. PMID- 27253873 TI - Adipogenesis and aldosterone: a study in lean tryptophan-depleted rats. AB - Next to epithelial tissues, mineralocorticoid receptors are also expressed in adipose tissue and are involved in the process of adipogenesis. Mineralocorticoid receptors in adipose tissue are likely to be activated mainly by glucocorticoids. The aim of the present study was to test the hypothesis that the processes related to adipogenesis are modified under the conditions associated with high circulating aldosterone. We have made advantage of a model of depression based on tryptophan depletion in which we have previously demonstrated that the elevation of serum aldosterone precedes that of corticosterone. Sixty adult female Sprague Dawley rats were fed either a low tryptophan diet or control diet for 4 (elevation of aldosterone only), 7 and 14 days (broader neuroendocrine activation) respectively. Gene expression of several adipogenic factors, CD31, interleukin-6, adiponectin, resistin and leptin were evaluated. Levels of mRNAs coding for adipogenic, angiogenic and inflammatory factors in adipose tissue were elevated at 4 and 7 days of tryptophan depletion. Additionally, gene expression of aldosterone sensing 11-beta-hydroxysteroid dehydrogenase 2 and mineralocorticoid receptors were elevated. All changes disappeared at 14 days of tryptophan depletion. Synchronously an increase of adipose tissue mass was observed. Although direct evidence is not provided, observed changes in gene expression may be related to the action of aldosterone on mineralocorticoid receptors. Our findings represent the first data on any changes in gene expression in adipose tissue in animal models of depression. PMID- 27253872 TI - Genome Assembly of the Fungus Cochliobolus miyabeanus, and Transcriptome Analysis during Early Stages of Infection on American Wildrice (Zizania palustris L.). AB - The fungus Cochliobolus miyabeanus causes severe leaf spot disease on rice (Oryza sativa) and two North American specialty crops, American wildrice (Zizania palustris) and switchgrass (Panicum virgatum). Despite the importance of C. miyabeanus as a disease-causing agent in wildrice, little is known about either the mechanisms of pathogenicity or host defense responses. To start bridging these gaps, the genome of C. miyabeanus strain TG12bL2 was shotgun sequenced using Illumina technology. The genome assembly consists of 31.79 Mbp in 2,378 scaffolds with an N50 = 74,921. It contains 11,000 predicted genes of which 94.5% were annotated. Approximately 10% of total gene number is expected to be secreted. The C. miyabeanus genome is rich in carbohydrate active enzymes, and harbors 187 small secreted peptides (SSPs) and some fungal effector homologs. Detoxification systems were represented by a variety of enzymes that could offer protection against plant defense compounds. The non-ribosomal peptide synthetases and polyketide synthases (PKS) present were common to other Cochliobolus species. Additionally, the fungal transcriptome was analyzed at 48 hours after inoculation in planta. A total of 10,674 genes were found to be expressed, some of which are known to be involved in pathogenicity or response to host defenses including hydrophobins, cutinase, cell wall degrading enzymes, enzymes related to reactive oxygen species scavenging, PKS, detoxification systems, SSPs, and a known fungal effector. This work will facilitate future research on C. miyabeanus pathogen associated molecular patterns and effectors, and in the identification of their corresponding wildrice defense mechanisms. PMID- 27253874 TI - Site-Specific Turn-On Fluorescent Labeling of DNA-Interacting Protein Using Oligodeoxynucleotides That Modify Lysines To Produce 5,6-Dimethoxy 3 Methyleneisoindolin-1-one. AB - We have developed oligodeoxynucleotides (ODNs) that modify primary amines to produce 5,6-dimethoxy 3-methyleneisoindolin-1-one. Compared to the oxygen isosteric fluorophore, 4,5-dimethoxyphthalimide, this methyleneisoindolinone was more stable and exhibited an 85 nm blue-shifted fluorescent emission (lambdamax at 425 nm) with an intensity comparable to that of the phthalimide. Reaction of the DNA-binding domain of Escherichia coli DnaA protein with an ODN containing its binding sequence efficiently afforded a modified fluorescent protein at a specific lysine residue in the proximity of the ODN. A full-length DnaA protein was also successfully fluorescently labeled. These results demonstrate the potential utility of the ODNs developed in this study for the fluorescent labeling of DNA-interacting protein at the lysine residue of interest. PMID- 27253875 TI - Correction: Hydrophobicity of Antifungal beta-Peptides Is Associated with Their Cytotoxic Effect on In Vitro Human Colon Caco-2 and Liver HepG2 Cells. AB - [This corrects the article DOI: 10.1371/journal.pone.0149271.]. PMID- 27253876 TI - Insertion and Deletion Mismatches Distant from the Target Position Improve Gene Correction with a Tailed Duplex. AB - A 5'-tailed duplex (TD) DNA corrects a base-substitution mutation. In this study, the effects of insertion and deletion (indel) mismatches distant from the target position on the gene correction were examined. Three target plasmid DNAs with and without indel mismatches ~330 bases distant from the correction target position were prepared, and introduced into HeLa cells together with the TD. The indel mismatches improved the gene correction efficiency and specificity without sequence conversions at the indel mismatch site. These results suggested that the gene correction efficiency and specificity are increased when an appropriate second mismatch is introduced into the TD fragment. PMID- 27253877 TI - The Spreading of Social Energy: How Exposure to Positive and Negative Social News Affects Behavior. AB - Social news, unlike video games or TV programs, conveys real-life interactions. Theoretically, social news in which people help or harm each other and violate rules should influence both prosocial and violation behaviors. In two experiments, we demonstrated the spreading effects of social news in a social interaction context emphasizing social conventions and a nonsocial interaction context emphasizing moral norms. Across the two studies, the results showed that positive social news increased cooperation (decreased defection) but had no effect on cheating, whereas negative social news increased cheating but with no change in cooperation (or defection). We conclude that there is a spreading impact of positive social news in the conventional norm domain and of negative social news in the moral norm domain. PMID- 27253879 TI - Does the scientific underpinning of regulatory tools to estimate bioavailability of nickel in freshwaters matter? The European-wide environmental quality standard for nickel. AB - A bioavailability-based environmental quality standard (EQS) was established for nickel in freshwaters under the European Union's Water Framework Directive. Bioavailability correction based on pH, water hardness, and dissolved organic carbon is a demonstrable improvement on existing hardness-based quality standards, which may be underprotective in high-hardness waters. The present study compares several simplified bioavailability tools developed to implement the Ni EQS (biomet, M-BAT, and PNECPro) against the full bioavailability normalization procedure on which the EQS was based. Generally, all tools correctly distinguished sensitive waters from insensitive waters, although with varying degrees of accuracy compared with full normalization. Biomet and M-BAT predictions were consistent with, but less accurate than, full bioavailability normalization results, whereas PNECpro results were generally more conservative. The comparisons revealed important differences in tools in development, which results in differences in the predictions. Importantly, the models used for the development of PNECpro use a different ecotoxicity dataset, and a different bioavailability normalization approach using fewer biotic ligand models (BLMs) than that used for the derivation of the Ni EQS. The failure to include all of the available toxicity data, and all of the appropriate NiBLMs, has led to some significant differences between the predictions provided by PNECpro and those calculated using the process agreed to in Europe under the Water Framework Directive and other chemicals management programs (such as REACH). These considerable differences mean that PNECpro does not reflect the behavior, fate, and ecotoxicity of nickel, and raises concerns about its applicability for checking compliance against the Ni EQS. Environ Toxicol Chem 2016;35:2397-2404. (c) 2016 SETAC. PMID- 27253878 TI - Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana. AB - Eukaryotic genomes are regulated by epigenetic marks that act to modulate transcriptional control as well as to regulate DNA replication and repair. In Arabidopsis thaliana, mutation of the ATXR5 and ATXR6 histone methyltransferases causes reduction in histone H3 lysine 27 monomethylation, transcriptional upregulation of transposons, and a genome instability defect in which there is an accumulation of excess DNA corresponding to pericentromeric heterochromatin. We designed a forward genetic screen to identify suppressors of the atxr5/6 phenotype that uncovered loss-of-function mutations in two components of the TREX 2 complex (AtTHP1, AtSAC3B), a SUMO-interacting E3 ubiquitin ligase (AtSTUbL2) and a methyl-binding domain protein (AtMBD9). Additionally, using a reverse genetic approach, we show that a mutation in a plant homolog of the tumor suppressor gene BRCA1 enhances the atxr5/6 phenotype. Through characterization of these mutations, our results suggest models for the production atxr5 atxr6 induced extra DNA involving conflicts between the replicative and transcriptional processes in the cell, and suggest that the atxr5 atxr6 transcriptional defects may be the cause of the genome instability defects in the mutants. These findings highlight the critical intersection of transcriptional silencing and DNA replication in the maintenance of genome stability of heterochromatin. PMID- 27253880 TI - Activated Microporous Carbon Derived from Almond Shells for High Energy Density Asymmetric Supercapacitors. AB - Via the activation treatment of carbonized almond shells with HNO3 and KOH, activated microporous carbon (AMC-3 and AMC-2) was successfully synthesized. These two AMC electrodes demonstrate remarkable electrochemical behaviors such as high rate capability, high specific capacitance, and excellent cycle stability when serving as electrodes for supercapacitors. More importantly, through the use of a Zn-Ni-Co ternary oxide (ZNCO) positive electrode and the AMC negative electrode, asymmetric supercapacitors (ASC) were assembled that deliver superior energy density (53.3 Wh kg(-1) at a power density of 1126.1 W kg(-1) for ASC-2 and 53.6 Wh kg(-1) at a power density of 1124.5 W kg(-1) for ASC-3) and excellent stability (82.7% and 83.4% specific capacitance retention for ZNCO//AMC ASC-2 and ZNCO//AMC ASC-3, respectively, after 5000 cycles). Through these two methods, low cost, renewable, and environmentally friendly electrode materials can be provided for high energy density supercapacitors. PMID- 27253881 TI - Plasmodium falciparum Hep1 Is Required to Prevent the Self Aggregation of PfHsp70 3. AB - The majority of mitochondrial proteins are encoded in the nucleus and need to be imported from the cytosol into the mitochondria, and molecular chaperones play a key role in the efficient translocation and proper folding of these proteins in the matrix. One such molecular chaperone is the eukaryotic mitochondrial heat shock protein 70 (Hsp70); however, it is prone to self-aggregation and requires the presence of an essential zinc-finger protein, Hsp70-escort protein 1 (Hep1), to maintain its structure and function. PfHsp70-3, the only Hsp70 predicted to localize in the mitochondria of P. falciparum, may also rely on a Hep1 orthologue to prevent self-aggregation. In this study, we identified a putative Hep1 orthologue in P. falciparum and co-expression of PfHsp70-3 and PfHep1 enhanced the solubility of PfHsp70-3. PfHep1 suppressed the thermally induced aggregation of PfHsp70-3 but not the aggregation of malate dehydrogenase or citrate synthase, thus showing specificity for PfHsp70-3. Zinc ions were indeed essential for maintaining the function of PfHep1, as EDTA chelation abrogated its abilities to suppress the aggregation of PfHsp70-3. Soluble and functional PfHsp70-3, acquired by co-expression with PfHep-1, will facilitate the biochemical characterisation of this particular Hsp70 protein and its evaluation as a drug target for the treatment of malaria. PMID- 27253882 TI - Is the assessment of submucosal invasion still useful in the management of early rectal cancer? A study of 91 consecutive patients. AB - AIM: The only studies on the prognosis of T1 tumours are old and investigate colic and rectal cancers. Very few studies use Kikuchi's classification (of dividing submucosa into three strata) to evaluate the depth of the submucosal invasion. This study aimed to assess the pathological risk factors for lymph node metastasis (LNM), and the pathological and oncological results of patients with early rectal cancer (ERC, pT1 tumour). METHOD: Between 2000 and 2014, 91 consecutive patients undergoing surgery [primary total mesorectal excision (TME) or local excision (LE) alone, or LE followed by TME] for ERC were included. RESULTS: Eighteen patients underwent LE, 22 underwent LE followed by TME and 51 underwent primary total TME. After TME (n = 73), 16 (23%) patients had LNM. The LNM rate was 15% for Sm1 tumours, 14% for Sm2 tumours and 30% for Sm3 tumours. In multivariate analysis, lymphovascular invasion (P = 0.027) and high tumour budding (P = 0.037) were the only independent factors predictive of LNM. The depth of submucosal invasion was not associated with an increased risk of LNM. After a mean follow up of 56 +/- 46 months, 5-year overall survival, specific survival and disease-free survival were, respectively, 82%, 93% and 75%. No significant difference of survival was found according to the depth of submucosal invasion or to the surgical management. CONCLUSION: Histological features seem to be stronger risk factors for LNM than depth of submucosal invasion. Considering the LNM rate, TME should be discussed after LE in terms of one of these pathological criteria. PMID- 27253883 TI - Biomarkers in sarcoidosis. AB - INTRODUCTION: Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis. Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science. Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers. PMID- 27253884 TI - Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease. AB - Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD. PMID- 27253885 TI - Monitoring and predicting the risk of violence in residential facilities. No difference between patients with history or with no history of violence. AB - BACKGROUND: Most people with mental disorders are not violent. However, the lack of specific studies in this area and recent radical changes in Italy, including the closure of six Forensic Mental Hospitals, has prompted a more detailed investigation of patients with aggressive behaviour. AIMS: To compare socio demographic, clinical and treatment-related characteristics of long-term inpatients with a lifetime history of serious violence with controls; to identify predictors of verbal and physical aggressive behaviour during 1-year follow-up. METHODS: In a prospective cohort study, patients living in Residential Facilities (RFs) with a lifetime history of serious violence were assessed with a large set of standardized instruments and compared to patients with no violent history. Patients were evaluated bi-monthly with MOAS in order to monitor any aggressive behaviour. RESULTS: The sample included 139 inpatients, 82 violent and 57 control subjects; most patients were male. The bi-monthly monitoring during the 1-year follow-up did not show any statistically significant differences in aggressive behaviour rates between the two groups. The subscale explaining most of the MOAS total score was aggression against objects, although verbal aggression was the most common pattern. Furthermore, verbal aggression was significantly associated with aggression against objects and physical aggression. CONCLUSIONS: Patients with a history of violence in RFs, where treatment and clinical supervision are available, do not show higher rates of aggressiveness compared to patients with no lifetime history of violence. Since verbal aggression is associated with more severe forms of aggression, prompt intervention is warranted to reduce the risk of escalation. PMID- 27253886 TI - Study of Pyridine-Mediated Electrochemical Reduction of CO2 to Methanol at High CO2 Pressure. AB - The recently proposed highly efficient route of pyridine-catalyzed CO2 reduction to methanol was explored on platinum electrodes at high CO2 pressure. At 55 bar (5.5 MPa) of CO2 , the bulk electrolysis in both potentiostatic and galvanostatic regimes resulted in methanol production with Faradaic yields of up to 10 % for the first 5-10 C cm(-2) of charge passed. For longer electrolysis, the methanol concentration failed to increase proportionally and was limited to sub-ppm levels irrespective of biasing conditions and pyridine concentration. This limitation cannot be removed by electrode reactivation and/or pre-electrolysis and appears to be an inherent feature of the reduction process. In agreement with bulk electrolysis findings, the CV analysis supported by simulation indicated that hydrogen evolution is still the dominant electrode reaction in pyridine containing electrolyte solution, even with an excess CO2 concentration in the solution. No prominent contribution from either a direct or coupled CO2 reduction was found. The results obtained suggest that the reduction of CO2 to methanol is a transient process that is largely decoupled from the electrode charge transfer. PMID- 27253888 TI - Autoregressive linear least square single scanning electron microscope image signal-to-noise ratio estimation. AB - A technique based on linear Least Squares Regression (LSR) model is applied to estimate signal-to-noise ratio (SNR) of scanning electron microscope (SEM) images. In order to test the accuracy of this technique on SNR estimation, a number of SEM images are initially corrupted with white noise. The autocorrelation function (ACF) of the original and the corrupted SEM images are formed to serve as the reference point to estimate the SNR value of the corrupted image. The LSR technique is then compared with the previous three existing techniques known as nearest neighbourhood, first-order interpolation, and the combination of both nearest neighborhood and first-order interpolation. The actual and the estimated SNR values of all these techniques are then calculated for comparison purpose. It is shown that the LSR technique is able to attain the highest accuracy compared to the other three existing techniques as the absolute difference between the actual and the estimated SNR value is relatively small. SCANNING 38:771-782, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27253887 TI - Recombinant L-Asparaginase from Zymomonas mobilis: A Potential New Antileukemic Agent Produced in Escherichia coli. AB - L-asparaginase is an enzyme used as a chemotherapeutic agent, mainly for treating acute lymphoblastic leukemia. In this study, the gene of L-asparaginase from Zymomonas mobilis was cloned in pET vectors, fused to a histidine tag, and had its codons optimized. The L-asparaginase was expressed extracellularly and intracellularly (cytoplasmically) in Escherichia coli in far larger quantities than obtained from the microorganism of origin, and sufficient for initial cytotoxicity tests on leukemic cells. The in silico analysis of the protein from Z. mobilis indicated the presence of a signal peptide in the sequence, as well as high identity to other sequences of L-asparaginases with antileukemic activity. The protein was expressed in a bioreactor with a complex culture medium, yielding 0.13 IU/mL extracellular L-asparaginase and 3.6 IU/mL intracellular L asparaginase after 4 h of induction with IPTG. The cytotoxicity results suggest that recombinant L-asparaginase from Z. mobilis expressed extracellularly in E.coli has a cytotoxic and cytostatic effect on leukemic cells. PMID- 27253889 TI - The Ubiquity of Chronic Illness. AB - This is a review of five different books dealing with some aspect of what might be termed a "chronic illness" - Alzheimer's disease, lupus, addiction, erectile dysfunction, and leprosy. The array of different subjects examined in these books points to the negotiable limits of this hugely open category. What exactly constitutes an "illness"? Why not use a less biomedical term instead: "disturbance", "problem", or simply "condition"? And how are we to understand "chronic" - simply as the flipside of "acute" or "curable"? PMID- 27253890 TI - Lack of Genetic Interaction between Tbx18 and Tbx2/Tbx20 in Mouse Epicardial Development. AB - The epicardium, the outermost layer of the heart, is an essential source of cells and signals for the formation of the cardiac fibrous skeleton and the coronary vasculature, and for the maturation of the myocardium during embryonic development. The molecular factors that control epicardial mobilization and differentiation, and direct the epicardial-myocardial cross-talk are, however, insufficiently understood. The T-box transcription factor gene Tbx18 is specifically expressed in the epicardium of vertebrate embryos. Loss of Tbx18 is dispensable for epicardial development, but may influence coronary vessel maturation. In contrast, over-expression of an activator version of TBX18 severely impairs epicardial development by premature differentiation of epicardial cells into SMCs indicating a potential redundancy of Tbx18 with other repressors of the T-box gene family. Here, we show that Tbx2 and Tbx20 are co expressed with Tbx18 at different stages of epicardial development. Using a conditional gene targeting approach we find that neither the epicardial loss of Tbx2 nor the combined loss of Tbx2 and Tbx18 affects epicardial development. Similarly, we observed that the heterozygous loss of Tbx20 with and without additional loss of Tbx18 does not impact on epicardial integrity and mobilization in mouse embryos. Thus, Tbx18 does not function redundantly with Tbx2 or Tbx20 in epicardial development. PMID- 27253891 TI - Three decades after Baby Doe: how neonatologists and bioethicists conceptualize the Best Interests Standard. AB - OBJECTIVE: The objective of this study is to determine how neonatologists and bioethicists conceptualize and apply the Best Interests Standard (BIS). STUDY DESIGN: Members of the American Society for Bioethics and Humanities and the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine were surveyed to determine how they conceptualized the BIS and ranked the appropriateness of forgoing life-sustaining therapy (LST). RESULTS: Neonatologists' median response supported an infant-specific BIS conceptualization that linked the infant's and family's interests. They did not support allowing limitations on the family's obligations. Ethicists' supported a conceptualization that linked the infant's and family's interests and limitations on the family's obligations, a less infant-specific conceptualization. Ethicists were less or equally likely to agree with forgoing LST in seven of eight cases. CONCLUSIONS: Ethicists endorsed a conceptualization of the BIS that includes the effects on the family and rejected an infant-specific one. Neonatologists split between these two and rejected limiting the family's obligations. Critical appraisal of the BIS is needed in neonatal ethics. PMID- 27253892 TI - Trial of labor after cesarean in the low-risk obstetric population: a retrospective nationwide cohort study. AB - OBJECTIVE: The purpose of this study was to evaluate the risk of adverse maternal outcomes associated with trial of labor (TOL) after cesarean during subsequent pregnancies in the low-risk population. STUDY DESIGN: We conducted a retrospective cohort study using the Nationwide Inpatient Sample and ICD-9 diagnostic and procedure codes from the years 2003 to 2011. A cohort of low-risk pregnant women with a history of previous cesarean delivery were identified and separated into two groups: TOL and no TOL. Logistic regression analysis was used to calculate odds ratios (ORs) comparing adverse maternal outcomes between these two groups. RESULTS: Out of 7 290 474 registered deliveries, there were 685 137 low-risk women who met inclusion criteria. Of these women, 144 066 (21.0%) underwent a TOL, with rates remaining steady over the course of our study. The TOL group was at increased risk of overall morbidity (OR 1.74, 95% confidence interval (CI), 1.66-1.79), most notably uterine rupture (OR 22.52, 95% CI, 19.35 26.20, P<0.01). A secondary analysis showed no apparent correlation between TOL and concomitant adverse maternal outcomes in cases of uterine rupture. CONCLUSION: Although these outcomes remain rare, low-risk women undergoing a TOL remain at increased risk of adverse maternal events as compared with those who chose elective repeat cesarean delivery. PMID- 27253893 TI - Mode of delivery and antenatal steroids and their association with survival and severe intraventricular hemorrhage in very low birth weight infants. AB - OBJECTIVE: To determine whether CS delivery and receipt of antenatal steroids (ANS) in vertex-presenting singletons with a gestational age (GA) between 24 and 30 weeks is associated with improved survival and improved severe intraventricular hemorrhage (sIVH)-free survival. STUDY DESIGN: Multicenter cohort, retrospective analysis of prospectively collected data. Vertex-presenting singletons newborns with GA 24 to 30 weeks, birth weight between 500 and 1500 g, without major congenital malformations, born between 2001 and 2011 at Neocosur centers were included. RESULTS: Four thousand three hundred and eighty-six infants fulfilled inclusion criteria: 45.8% were delivered vaginally and 54.2% by cesarean section (CS). Newborns delivered vaginally received less ANS, had lower GA, Apgar scores and a lower incidence of survival and sIVH-free survival (P<0.001). Newborns with better survival were those with ANS, independent of mode of delivery. At 24 to 25 weeks GA, increased survival and sIVH-free survival were associated with ANS and CS delivery, compared with those who received ANS and delivered vaginally. CONCLUSIONS: Among vertex-presenting singletons with GA 24 to 30 weeks, better survival and IVH-free survival were associated with ANS, independent of mode of delivery. In infants at 24 to 25 weeks gestation the combination of ANS/CS was associated with improvement in both outcomes. PMID- 27253894 TI - The effect of pasteurization on trace elements in donor breast milk. AB - OBJECTIVE: Premature infants often receive pasteurized donor human milk when mothers are unable to provide their own milk. This study aims to establish the effect of the pasteurization process on a range of trace elements in donor milk. STUDY DESIGN: Breast milk was collected from 16 mothers donating to the milk bank at the Royal Brisbane and Women's Hospital. Samples were divided into pre- and post-pasteurization aliquots and were Holder pasteurized. Inductively coupled plasma mass spectrometry was used to analyze the trace elements zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), iodine (I), iron (Fe), molybdenum (Mo) and bromine (Br). Differences in trace elements pre- and post-pasteurization were analyzed. RESULTS: No significant differences were found between the trace elements tested pre- and post-pasteurization, except for Fe (P<0.05). The median (interquartile range, 25 to 75%; MUg l(-1)) of trace elements for pre- and post- pasteurization aliquots were-Zn: 1639 (888-4508), 1743 (878-4143), Cu: 360 (258 571), 367 (253-531), Se: 12.34 (11.73-17.60), 12.62 (11.94-16.64), Mn: (1.48 (1.01-1.75), 1.49 (1.11-1.75), I (153 (94-189), 158 (93-183), Fe (211 (171-277), 194 (153-253), Mo (1.46 (0.37-2.99), 1.42 (0.29-3.73) and Br (1066 (834-1443), 989 (902-1396). CONCLUSIONS: Pasteurization had minimal effect on several trace elements in donor breast milk but high levels of inter-donor variability of trace elements were observed. The observed decrease in the iron content of pasteurized donor milk is, however, unlikely to be clinically relevant. PMID- 27253895 TI - Wound complications in obese women after cesarean: a comparison of staples versus subcuticular suture. AB - OBJECTIVE: To compare wound complications between staples versus subcuticular suture for skin closure in obese women (body mass index (BMI)?30 kg m(-2)) after cesarean delivery (CD). STUDY DESIGN: We conducted a retrospective cohort study to compare wound complications between staples and subcuticular suture closure in women, with a prepregnancy BMI?30 kg m(-2) after CD between 2006 and 2011 at an inner-city teaching hospital. Wound complication was defined as a composite of wound disruption (hematoma or seroma) or infection diagnosed up to 6 weeks postpartum. Variables collected include age, parity, prior CDs, prior abdominal surgeries, incision type, chorioamnionitis, maternal comorbidities (hypertension, diabetes) and gestational age. RESULTS: Of the 1147 women included in the study, women with staple closure were older and had higher BMIs (40.6+/-9.3 versus 36.1+/-5.4) and were more likely to be multiparous, have a prior CD, diabetes and hypertension compared with women with subcuticular suture. The overall occurrence of wound complications was 15.5% (178/1147). Women with staples had higher wound complications compared with sutures (22.0% versus 9.7%) with a 2.27 unadjusted relative risk (RR) (95% confidence interval (CI), 1.7 to 3.0) and 1.78 adjusted RR (95% CI, 1.27 to 2.49) after controlling for confounders in the final analysis, including vertical skin incisions. CONCLUSIONS: In obese women, skin closure with staples at the time of CD is associated with a higher rate of wound complications compared with subcuticular suture. Skin closure with subcuticular suture over staples should be considered in obese women undergoing a CD regardless of skin incision type. PMID- 27253896 TI - Controlled n-Type Doping of Carbon Nanotube Transistors by an Organorhodium Dimer. AB - Single-walled carbon nanotube (SWCNT) transistors are among the most developed nanoelectronic devices for high-performance computing applications. While p-type SWCNT transistors are easily achieved through adventitious adsorption of atmospheric oxygen, n-type SWCNT transistors require extrinsic doping schemes. Existing n-type doping strategies for SWCNT transistors suffer from one or more issues including environmental instability, limited carrier concentration modulation, undesirable threshold voltage control, and/or poor morphology. In particular, commonly employed benzyl viologen n-type doping layers possess large thicknesses, which preclude top-gate transistor designs that underlie high density integrated circuit layouts. To overcome these limitations, we report here the controlled n-type doping of SWCNT thin-film transistors with a solution processed pentamethylrhodocene dimer. The charge transport properties of organorhodium-treated SWCNT thin films show consistent n-type behavior when characterized in both Hall effect and thin-film transistor geometries. Due to the molecular-scale thickness of the organorhodium adlayer, large-area arrays of top gated, n-type SWCNT transistors are fabricated with high yield. This work will thus facilitate ongoing efforts to realize high-density SWCNT integrated circuits. PMID- 27253897 TI - Correcting for H2O interference using a RAD7 electrostatic collection-based silicon detector. AB - The effect of water molecules on the electrostatic collection of 218Po ions onto the surface of silicon detectors (neutralization) is evaluated through the comparison with a scintillation cell (ZnS), not affected by air humidity. A radon monitor (RAD7, Durridge Company) was connected to a stainless steel radon chamber, equipped with the scintillation cell. Radon gas, extracted from an acidified RaCl2 source, was injected into the chamber and the amount of water molecules in the system was alternatively lowered or increased (from 0.00075 to 0.014 g of water in RAD7) by connecting the chamber to a desiccant or to a bubbling water bottle. The relative efficiency of the silicon detector with respect to the scintillation cell decreases with the growth of water molecules inside RAD7. This dependence, with a fixed i) electrostatic chamber geometry and ii) nominal high voltage, diverges during the humidification or the drying phase because it is in turn influenced by the length of interaction of polonium atoms with water molecules, which impacts on the size of 218Po clusters and thus on the neutralization process. For water contents higher that 0.01 g in RAD7, this effect is greatly enhanced. Temperature in the investigated range (18.5-35.6 degrees C) does not affect the efficiency of electrostatic collection-based silicon detectors. Based on these experiments, admitting a certain error on the efficiency (from 1.8 to 7.5%, depending on the water content), proper corrections were developed to adjust soil radon readings, when a desiccant is removed. This operation is necessary if recent Non-Aqueous Phase Liquids (NAPLs) leakage has occurred in the subsoil to avoid the sorption and possible later release of radon by Drierite, with related partition between the solid and liquid phases (water and NAPL). PMID- 27253898 TI - Rhodium-Catalyzed Enantioselective Silylation of Cyclopropyl C-H Bonds. AB - Hydrosilyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields and with high enantiomeric excesses in the presence of a rhodium catalyst derived from a rhodium precursor and the bisphosphine (S)-DTBM-SEGPHOS. The resulting enantioenriched oxasilolanes are suitable substrates for the Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee value from the C-H silylation. Preliminary mechanistic data suggest that C-H cleavage is likely to be the turnover-limiting and enantioselectivity-determining step. PMID- 27253899 TI - Access to childbirth care by adolescents and young people in the Northeastern region of Brazil. AB - OBJECTIVE: To identify the factors that interfere with the access of adolescents and young people to childbirth care for in the Northeast region of Brazil. METHODS: Cross-sectional study with 3,014 adolescents and young people admitted to the selected maternity wards to give birth in the Northeast region of Brazil. The sample design was probabilistic, in two stages: the first corresponded to the health establishments and the second to women who had recently given birth and their babies. The data was collected by means of interviews and consulting the hospital records, from pre-tested electronic form. Descriptive statistics were used for the univariate analysis, Pearson's Chi-square test for the bivariate analysis and multiple logistic regressions for the multivariate analysis. Sociodemographic variables, obstetrical history, and birth care were analyzed. RESULTS: Half of the adolescents and young people interviewed had not been given guidance on the location that they should go to when in labor, and among those who had, 23.5% did not give birth in the indicated health service. Furthermore, one third (33.3%) had to travel in search of assisted birth, and the majority (66.7%) of the postpartum women came to maternity by their own means. In the bivariate analysis, the variables marital status, paid work, health insurance, number of previous pregnancies, parity, city location, and type of health establishment showed a significant association (p < 0.20) with inadequate access to childbirth care. The multivariate analysis showed that married adolescents and young people (p < 0.015), with no health insurance (p < 0.002) and from the countryside (p < 0.001) were more likely to have inadequate access to childbirth care. CONCLUSIONS: Adolescents and young women, married, without health insurance, and from the countryside are more likely to have inadequate access to birth care. The articulation between outpatient care and birth care can improve this access and, consequently, minimize the maternal and fetal risks that arise from a lack of systematic hospitalization planning. PMID- 27253900 TI - Exposure to psychosocial risk factors in the context of work: a systematic review. AB - OBJECTIVE: To analyze the scientific literature about the effects of exposure to psychosocial risk factors in work contexts. METHODS: A systematic review was performed using the terms "psychosocial factors" AND "COPSOQ" in the databases PubMed, Medline, and Scopus. The period analyzed was from January 1, 2004 to June 30, 2012. We have included articles that used the Copenhagen Psychosocial Questionnaire (COPSOQ) as a measuring instrument of the psychosocial factors and the presentation of quantitative or qualitative results. German articles, psychometric studies or studies that did not analyze individual or work factors were excluded. RESULTS: We included 22 articles in the analysis. Individual factors, such as gender, age, and socioeconomic status, were analyzed along with work-related factors such as labor demands, work organization and content, social relationships and leadership, work-individual interface, workplace values, justice and respect, personality, health and well-being, and offensive behaviors. We analyzed the sample type and the applied experimental designs. Some population groups, such as young people and migrants, are more vulnerable. The deteriorated working psychosocial environment is associated with physical health indicators and weak mental health. This environment is also a risk factor for the development of moderate to severe clinical conditions, predicting absenteeism or intention of leaving the job. CONCLUSIONS: The literature shows the contribution of exposure to psychosocial risk factors in work environments and their impact on mental health and well-being of workers. It allows the design of practical interventions in the work context to be based on scientific evidences. Investigations in specific populations, such as industry, and studies with more robust designs are lacking. PMID- 27253901 TI - Safety and efficacy of fenproporex for obesity treatment: a systematic review. AB - OBJECTIVE: To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS: MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS: Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS: There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern. PMID- 27253902 TI - Hospitalization due to drug use did not change after a decade of the Psychiatric Reform. AB - OBJECTIVE: To investigate whether the psychiatric hospitalization rates due to use of psychoactive substances and average time of hospitalization suffered any changes after the first decade of effective implementation of the psychiatric reform in Brazil. METHODS: This article examines the evolution of hospitalizations due to disorders arising from the use of alcohol or other substances in the state of Santa Catarina, Southern Brazil, from 2000 to 2012. This is an ecological, time-series study, which uses data from admissions obtained by the Informatics Service of the Brazilian Unified Health System. Hospitalization rates by 100,000 inhabitants and average time of occupancy of beds were estimated. Coefficients of variation of these rates were estimated by Poisson Regression. RESULTS: The total and male hospitalization rates did not vary (p = 0.056 and p = 0.244, respectively). We observed an increase of 3.0% for the female sex (p = 0.049). We did not observe any significant variation for occupancy time of beds. CONCLUSIONS: The deployment of services triggered by the Brazilian psychiatric reform was not accompanied by a reduction of hospitalization rates or mean occupancy time of hospitalized patients during this first decade of implementation of the reform. PMID- 27253903 TI - Prevalence of hypertension among adolescents: systematic review and meta analysis. AB - OBJECTIVE: To estimate the prevalence of hypertension among adolescent Brazilian students. METHODS: A systematic review of school-based cross-sectional studies was conducted. The articles were searched in the databases MEDLINE, Embase, Scopus, LILACS, SciELO, Web of Science, CAPES thesis database and Trip Database. In addition, we examined the lists of references of relevant studies to identify potentially eligible articles. No restrictions regarding publication date, language, or status applied. The studies were selected by two independent evaluators, who also extracted the data and assessed the methodological quality following eight criteria related to sampling, measuring blood pressure, and presenting results. The meta-analysis was calculated using a random effects model and analyses were performed to investigate heterogeneity. RESULTS: We retrieved 1,577 articles from the search and included 22 in the review. The included articles corresponded to 14,115 adolescents, 51.2% (n = 7,230) female. We observed a variety of techniques, equipment, and references used. The prevalence of hypertension was 8.0% (95%CI 5.0-11.0; I2 = 97.6%), 9.3% (95%CI 5.6-13.6; I2 = 96.4%) in males and 6.5% (95%CI 4.2-9.1; I2 = 94.2%) in females. The meta regression failed to identify the causes of the heterogeneity among studies. CONCLUSIONS: Despite the differences found in the methodologies of the included studies, the results of this systematic review indicate that hypertension is prevalent in the Brazilian adolescent school population. For future investigations, we suggest the standardization of techniques, equipment, and references, aiming at improving the methodological quality of the studies. PMID- 27253904 TI - Molecular Crowding Effects on Microgel-Tethered Oligonucleotide Probes. AB - Microgel tethering is a nontraditional method with which to bind oligonucleotide hybridization probes to a solid surface. Microgel-tethering physically positions the probes away from the underlying hard substrate and maintains them in a highly waterlike environment. This paper addresses the question of whether molecular crowding affects the performance of microgel-tethered molecular beacon probes. The density of probe-tethering sites is controlled experimentally using thin-film blends of biotin-terminated [PEG-B] and hydroxyl-terminated [PEG-OH] poly(ethylene glycol) from which microgels are synthesized and patterned by electron beam lithography. Fluorescence measurements indicate that the number of streptavidins, linear DNA probes, hairpin probes, and molecular beacon probes bound to the microgels increases linearly with increasing PEG-B/PEG-OH ratio. For a given tethering-site concentration, more linear probes can bind than structured probes. Crowding effects emerge during the hybridization of microgel-tethered molecular beacons but not during the hybridization of linear probes, as the tethering density increases. Crowding during hybridization is associated with conformational constraints imposed by the close proximity of closed and hybridized structured probes. The signal-to-background ratio (SBR) of hybridized beacons is highest and roughly constant for low tethering densities and decreases at the highest tethering densities. Despite differences between microgel tethering and traditional oligonucleotide surface-immobilization approaches, these results show that crowding defines an optimum tethering density for molecular beacon probes that is less than the maximum possible, which is consistent with previous studies involving various linear and structured oligonucleotide probes. PMID- 27253905 TI - Association of Facial Paralysis-Related Disability With Patient- and Observer Perceived Quality of Life. AB - IMPORTANCE: The interaction between patient- and observer-perceived quality of life (QOL) and facial paralysis-related disability and the resulting effect of these interactions on social perception are incompletely understood. OBJECTIVE: To measure the associations between observer-perceived disability and QOL and patient-perceived disability and QOL in patients with facial paralysis. DESIGN, SETTING, AND PARTICIPANTS: This prospective study in an academic tertiary referral center included 84 naive observers who viewed static and dynamic images of faces with unilateral, House-Brackmann grades IV to VI facial paralysis (n = 16) and demographically matched images of nonparalyzed control individuals (n = 4). Data were collected from June 1 to August 1, 2014, and analyzed from August 2 to December 1, 2014. MAIN OUTCOMES AND MEASURES: Observers rated the patient and control images in 6 clinically relevant domains. The patients self-reported their disability and QOL using validated tools, such as the Facial Clinimetric Evaluation Scale. Quality of life, severity of paralysis, and disability were measured on a 100-point visual analog scale. RESULTS: The 84 observers (59 women [70%] and 25 men [30%]) ranged in age from 20 to 68 years (mean [SD] age, 35.2 [11.9]). Structural equation modeling showed that for each 1-point decrease in a patient's Facial Clinimetric Evaluation Scale score, the patient's visual analog scale QOL improved by 0.36 (SE, 0.03; 95% CI, 0.31-0.42) points. Similarly, from an observer perspective, as the perceived disability (-0.29 [SE, 0.04; 95% CI, 0.36 to -0.22]) and severity (-0.21 [SE, 0.03; 95% CI, -0.28 to -0.14]) decreased, the perceived QOL improved. Furthermore, attractive faces were viewed as having better QOL (disability, severity, and attractiveness regression coefficients, -0.29 [SE, 0.04; 95% CI, -0.36 to -0.22], -0.21 [SE, 0.03; 95% CI, 0.28 to -0.14], and 0.32 [SE, 0.03; 95% CI, 0.26 to 0.39], respectively). An inverse association was found between a paralyzed patient's self-reported QOL rating and the observers' perceived QOL. This association was complex and was mediated through perceived severity and disability. Observers judged the severity of paralyzed faces to be 3.61 (SE, 1.80; 95% CI, 0.09-7.14) points more severe when viewing dynamic rather than static images. CONCLUSIONS AND RELEVANCE: Observers were more likely to rate QOL lower owing to disability than were the patients with paralysis. This finding may be explained by previous literature reporting that disabled people adjust their values to accommodate their disability, thereby limiting the negative effect on their QOL. Given the importance of QOL on social interaction, the dissonance between observers and patients in this area has important implications for the socialization of patients with facial paralysis. LEVEL OF EVIDENCE: NA. PMID- 27253906 TI - The imperiled fish fauna in the Nicaragua Canal zone. AB - Large-scale infrastructure projects commonly have large effects on the environment. The planned construction of the Nicaragua Canal will irreversibly alter the aquatic environment of Nicaragua in many ways. Two distinct drainage basins (San Juan and Punta Gorda) will be connected and numerous ecosystems will be altered. Considering the project's far-reaching environmental effects, too few studies on biodiversity have been performed to date. This limits provision of robust environmental impact assessments. We explored the geographic distribution of taxonomic and genetic diversity of freshwater fish species (Poecilia spp., Amatitlania siquia, Hypsophrys nematopus, Brycon guatemalensis, and Roeboides bouchellei) across the Nicaragua Canal zone. We collected population samples in affected areas (San Juan, Punta Gorda, and Escondido drainage basins), investigated species composition of 2 drainage basins and performed genetic analyses (genetic diversity, analysis of molecular variance) based on mitochondrial cytb. Freshwater fish faunas differed substantially between drainage basins (Jaccard similarity = 0.33). Most populations from distinct drainage basins were genetically differentiated. Removing the geographic barrier between these basins will promote biotic homogenization and the loss of unique genetic diversity. We found species in areas where they were not known to exist, including an undescribed, highly distinct clade of live bearing fish (Poecilia). Our results indicate that the Nicaragua Canal likely will have strong impacts on Nicaragua's freshwater biodiversity. However, knowledge about the extent of these impacts is lacking, which highlights the need for more thorough investigations before the environment is altered irreversibly. PMID- 27253907 TI - A combined disc method with resazurin agar plate assay for early phenotypic screening of KPC, MBL and OXA-48 carbapenemases among Enterobacteriaceae. AB - AIM: To validate a combined disc method along with resazurin chromogenic agar for early screening and differentiation of Klebsiella pneumoniae carbapenemase, metallo-beta-lactamase and OXA-48 carbapenemase-producing Enterobacteriaceae. METHODS AND RESULTS: The combined disc test comprising of meropenem alone and with EDTA, phenylboronic acid or both EDTA and phenylboronic acid, and temocillin alone were evaluated with the resazurin chromogenic agar plate assay against a total of 86 molecularly confirmed Enterobacteriaceae clinical isolates (11 metallo-beta-lactamases, eight Kl. pneumoniae carbapenemases, 11 OXA-48, 32 AmpC and 15 extended-spectrum-beta-lactamase producers and nine co-producers of extended-spectrum-beta-lactamase and AmpC). The inhibition zone diameters were measured and interpreted at 7 h for the presence of carbapenemase. All carbapenemase producers were phenotypically distinguished by this assay with 100% sensitivity and specificity. CONCLUSIONS: This early phenotypic method is very simple, inexpensive, and reliable in the detection and differentiation of carbapenemase-producing Enterobacteriaceae. It could be exploited in any microbiological laboratory for diagnosis of these recalcitrant bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: This assay poses excellent performance in discrimination of Kl. pneumoniae carbapenemase, metallo-beta-lactamase and OXA-48 carbapenemases within 7 h, which is much faster than conventional disc diffusion methods. The rapid detection could help clinicians screen patients, control infection and provide epidemiological surveillance. PMID- 27253908 TI - Advances in Transition-Metal-Catalysed Alkyne Hydroarylations. AB - We present herein a personal account of our achievements in the development of novel catalytic systems based on late-transition-metal complexes for the hydroarylation of alkynes. In particular, our targets were intermolecular hydroarylation reactions with arene or heteroarene substrates devoid of directing groups. We have shown that complexes of palladium, platinum or gold with N heterocyclic carbene (NHC) ligands can be particularly useful catalysts for this reaction; the NHC ligand imparts greater stability to the complex and renders the catalytic system more productive. Furthermore, we have identified promoters and reaction media that allow to significantly improve the catalytic activity under mild conditions, to control the reaction chemoselectivity and to steer it towards more complex products; thus making this reaction considerably more attractive for the synthetic chemist. PMID- 27253910 TI - Incidental Finding in a Man With Objective Tinnitus. PMID- 27253909 TI - Tracing the locality of prisoners and workers at the Mausoleum of Qin Shi Huang: First Emperor of China (259-210 BC). AB - The mausoleum complex of the First Emperor of China, Qin Shi Huang (259-210 BC), is one of the most famous and important archaeological sites in China, yet questions remain as to how it was constructed and by whom. Here we present isotopic results of individuals from the Liyi (n = 146) and Shanren sites (n = 14), both associated with the mausoleum complex. Those buried at Liyi represent the local workers/inhabitants of the Qin population, and the delta(13)C (-8.7 +/- 1.5%) and delta(15)N (10.3 +/- 0.7%) values indicate that they consumed predominately millet and/or domestic animals fed millet. In contrast, the Shanren individuals were prisoners forced to construct the mausoleum (found buried haphazardly in a mass grave and some in iron leg shackles), and their delta(13)C (-15.4 +/- 2.9%) and delta(15)N (8.0 +/- 0.6%) results indicate a more mixed C3/C4 diet, with possibly less domestic animals and more wild game protein consumed. This pattern of decreased millet consumption is also characteristic of archaeological sites from southern China, and possible evidence the Shanren prisoners originated from this region (possibly the ancient Chu state located in modern day Hubei Province and parts of Hunan and Anhui Provinces). Further, this finding is in agreement with historical sources and is supported by previous ancient DNA evidence that the mausoleum workers had diverse origins, with many genetically related to southern Chinese groups. PMID- 27253911 TI - Differentiating between benign follicular nodules and follicular neoplasms in thyroid liquid-based cytology preparations. AB - BACKGROUND: The cytological morphology observed in liquid-based cytology (LBC) preparations is dissimilar to that of conventional preparations. The aim of this report is to clarify the cytological differences between benign follicular nodules (BFNs) and follicular neoplasms (FNs) in LBC preparations and identify novel diagnostic criteria for LBC preparations. METHODS: A retrospective review of LBC preparations from 38 BFN and 74 FN (57 follicular adenomas and 17 follicular carcinomas) cases confirmed by histological examination was conducted. LBC samples were obtained from the washout fluid in aspiration needles, fixed with CytoRich-RED(TM) , and prepared using the SurePath(TM) method. RESULTS: Fibrin was observed in 43.2% of FNs and in 23.7% of BFNs. The incidences of intercellular spaces, distinct outer margin, and cytoplasmic process were significantly higher in BFNs (P < 0.01, P < 0.01, and P < 0.05, respectively). Elongated microfollicles were seen in 55.4% of FNs and 10.5% of BFNs (P < 0.01). Membranous materials encircling the outer edge of the follicles were observed only in BFN cases (5.8%). There were no significant differences between follicular adenoma and carcinoma. CONCLUSION: Intercellular spaces, distinct outer margins of the follicular clusters, cytoplasmic process, and membranous materials constitute indicators of BFN in LBC preparations. Fibrin and elongated microfollicles point to FN. We believe that these findings will improve the diagnostic accuracy of thyroid LBC preparations. Diagn. Cytopathol. 2016;44:659 664. (c) 2016 Wiley Periodicals, Inc. PMID- 27253912 TI - Effects of continuous positive airway pressure on diaphragmatic kinetics and breathing pattern in healthy individuals. AB - BACKGROUND AND OBJECTIVE: In this study, we investigate the changes in diaphragmatic kinetics, breathing pattern and work of breathing induced by 10 cmH2 O of continuous positive airway pressure (CPAP). METHODS: We used sonography to study diaphragmatic kinetics and measured energy expenditure using indirect calorimetry in 50 healthy volunteers at 0 cmH2 O positive end expiratory pressure (ZEEP) and after application of 10 cmH2 O CPAP. In a subgroup of 14 subjects, the changes in thoracic and abdominal volumes and thoraco-abdominal asynchrony were recorded with inductive plethysmography, while accessory respiratory muscle activity was recorded with electromyography. RESULTS: Continuous positive airway pressure breathing induced acute lung hyperinflation of 600 mL above passive functional residual capacity. This hyperinflation induced changes in diaphragmatic kinetics and breathing pattern; diaphragmatic excursion, thickness and thickness ratio, tidal volume (Vt) and oxygen consumption (VO2) increased while respiratory rate decreased. The increase in Vt with CPAP was mainly due to rib cage contribution. Activation of the accessory inspiratory (scalene) and expiratory (transversus abdominis) muscles was recorded. The raised respiratory muscles workload induced an increase in VO2. CONCLUSION: In healthy volunteers, CPAP therapy leads to lung overdistention and recruitment of respiratory muscles. These mechanisms operate at a high energy cost. PMID- 27253913 TI - Electronic structure and optical properties of graphene/stanene heterobilayer. AB - The structural, electronic and optical properties of the graphene hybrid with stanene, the tin counterpart of graphene, are investigated by means of density functional calculation with the observation of band gap opening and enhanced visible light response. The lattice mismatch between graphene and stanene is taken into consideration and several stacking methods for model construction are proposed to study the possible effects. The Dirac feature can be observed in this bilayer system with relatively stronger interlayer interaction than weak van der Waals forces, which is ascribed to the unsaturated p orbital of stanene. Despite the mutual semi-metal nature of graphene and stanene, it is significant to note a band gap opening and the electrical neutrality of the bilayer. The combination of high carrier mobility of graphene and the excellent spin Hall effect of stanene is expected to coexist in the bilayer structure. In addition, we found that the stanene monolayer has a relatively lower work function than graphene and more importantly, it exhibits more pronounced optical absorption than graphene. The results indicate that a graphene/stanene heterobilayer will facilitate the performance of stanene related spintronic devices and is therefore a good candidate for photoelectronic devices. PMID- 27253914 TI - Development of a simple assay system for protein-stabilizing efficiency based on hemoglobin protection against denaturation and measurement of the cooperative effect of mixing protein stabilizers. AB - We have elucidated the cooperative stabilization of proteins by sugars, amino acids, and other protein-stabilizing agents using a new and simple assay system. Our system determines the protein-stabilizing ability of various compounds by measuring their ability to protect hemoglobin from denaturation. Hemoglobin denaturation was readily measured by quantitative changes in its ultraviolet visible absorption spectrum. The efficiency of our assay was confirmed using various sugars such as trehalose and sucrose that are known to be good protein stabilizers. We have also found that mixtures of two different types of protein stabilizers resulted in a cooperative stabilizing effect on protein. PMID- 27253968 TI - Long-term Follow-up of a Case of Gold Shunt Surgery for Refractory Silicone Oil induced Glaucoma. AB - PURPOSE: To report the first case of gold shunt surgery for treatment of silicone oil-induced refractory glaucoma in a tertiary care academic center, with 5-year follow-up. DESIGN: The study design is a case report. PARTICIPANTS: The participant was a patient who underwent gold shunt surgery. METHODS: Institutional Research Ethics Board approval for the study was obtained. A diabetic patient was referred for refractory glaucoma with a history of proliferative diabetic retinal detachment, and surgery with silicone oil. She was uncontrolled on maximal medical therapy and following informed consent, gold shunt surgery was performed. Ocular outcomes and number of medications were reviewed over a 5-year period. RESULTS: Following uncomplicated surgery, intraocular pressure was reduced from 41 to 14 mm Hg, and the number of medications was reduced from 4 to 1. Glaucomatous optic neuropathy remained stable. CONCLUSIONS: Gold shunt surgery in this challenging case of silicone oil refractory glaucoma provided long-term intraocular pressure control and reduced need for medication over a 5-year period. PMID- 27253969 TI - Evidence Supporting an Association Between Expression of Major Histocompatibility Complex II by Microglia and Optic Nerve Degeneration During Experimental Glaucoma. AB - AIM: We acquired age-matched and sex-matched Sprague-Dawley rats from 2 independent breeding establishments. Serendipitously, we observed that constitutive, and bacterial toxin-induced, expression of major histocompatibility complex (MHC) class II RT1B chain in the uveal tract was much lower in one of the cohorts. Activated microglia are known to upregulate MHC II RT1B expression during optic nerve (ON) degeneration induced by raised intraocular pressure (IOP). We investigated whether, in a model of experimental glaucoma, microglial upregulation of MHC II RT1B was less efficacious and ON degeneration correspondingly less severe in the cohort of rats with low MHC II RT1B expression. METHODS: Experimental glaucoma was induced by lasering the trabecular meshwork using a standard protocol. After 2 weeks of elevated IOP, retinal ganglion cells (RGC) survival, ON degeneration, and microglial responses were determined in both cohorts of rats. RESULTS: Raised IOP-induced expression of MHC II RT1B by microglia was muted in the "Low" cohort compared with the "High" cohort. Axonal degeneration, RGC loss, and microgliosis were all significantly lower in the cohort of rats with low basal and induced expression of MHC II RT1B, despite both cohorts displaying IOP responses that were indistinguishable in terms of peak IOP and IOP exposure. CONCLUSIONS: Expression of MHC II RT1B by activated microglia in the ON during experimental glaucoma was associated with more severe RGC degeneration. Further studies are needed to elucidate the role of MHC II during experimental glaucoma. PMID- 27253970 TI - Investigation of the photophysical and photochemical properties of peripherally tetra-substituted water-soluble zwitterionic and cationic zinc(ii) phthalocyanines. AB - In this study, 4-{4-[N-((3-dimethylamino)propyl)amide]phenoxy}phthalonitrile () and its zinc(ii) phthalocyanine derivative () were synthesized for the first time. 4-(N-((3-Dimethylamino)propyl)amide)phenoxy substituted zinc(ii) phthalocyanine () was converted to its water-soluble sulfobetaine (), betaine () and N-oxide () containing zwitterionic and quaternized cationic () derivatives. All newly synthesized compounds () were characterized by the combination of UV vis, FT-IR, (1)H NMR, mass spectroscopy techniques and elemental analysis. The photophysical (fluorescence quantum yields and lifetimes) and photochemical (singlet oxygen quantum yields) properties were investigated in DMSO for all the synthesized zinc(ii) phthalocyanines () and in both DMSO and aqueous solutions for zwitterionic and cationic phthalocyanines () for the specification of their capability as photosensitizers in photodynamic therapy (PDT). The binding behavior of water soluble phthalocyanines () to the bovine serum albumin protein was also examined for the determination of their transportation ability in the blood stream. PMID- 27253971 TI - Evidence for age-associated disinhibition of the wake drive provided by scoring principal components of the resting EEG spectrum in sleep-provoking conditions. AB - Age-associated changes in different bandwidths of the human electroencephalographic (EEG) spectrum are well documented, but their functional significance is poorly understood. This spectrum seems to represent summation of simultaneous influences of several sleep-wake regulatory processes. Scoring of its orthogonal (uncorrelated) principal components can help in separation of the brain signatures of these processes. In particular, the opposite age-associated changes were documented for scores on the two largest (1st and 2nd) principal components of the sleep EEG spectrum. A decrease of the first score and an increase of the second score can reflect, respectively, the weakening of the sleep drive and disinhibition of the opposing wake drive with age. In order to support the suggestion of age-associated disinhibition of the wake drive from the antagonistic influence of the sleep drive, we analyzed principal component scores of the resting EEG spectra obtained in sleep deprivation experiments with 81 healthy young adults aged between 19 and 26 and 40 healthy older adults aged between 45 and 66 years. At the second day of the sleep deprivation experiments, frontal scores on the 1st principal component of the EEG spectrum demonstrated an age-associated reduction of response to eyes closed relaxation. Scores on the 2nd principal component were either initially increased during wakefulness or less responsive to such sleep-provoking conditions (frontal and occipital scores, respectively). These results are in line with the suggestion of disinhibition of the wake drive with age. They provide an explanation of why older adults are less vulnerable to sleep deprivation than young adults. PMID- 27253972 TI - Current and future pharmacotherapy for treating overactive bladder. AB - INTRODUCTION: Drugs which prevent acetylcholine mediated involuntary detrusor contractions are the mainstay of overactive bladder(OAB) treatment but there are now several alternative therapeutic options available. AREAS COVERED: Current and future drug therapies for OAB are highlighted. These include novel antimuscarinic molecules (imidafenacin and tarafenacin); novel combination therapies with beta3 adrenoceptor agonists or muscarinic agonists (tolenix) and a novel vaginal delivery method for oxybutynin. beta3-adrenoceptor agonists(beta3-AR) have been shown to be efficiacious in the management of OAB. The evidence supporting the first licensed beta3-AR agonist, mirabegron, is assessed, as well as other putative beta3-AR agonists in development such as solabegron, ritobegron, aryloxypropanolamine, TRK-380, and CL 316,243. The role of vaginal oestrogen is highlighted followed by a detailed analysis of botulinum-A toxin. EXPERT OPINION: Anticholinergics were the first OAB drug therapy on the market and have the largest dataset available. Despite obvious limitations, these are still first line medical therapy. There are a number of new OAB therapies under investigation and we await their contribution to the management armamentarium. Other novel drugs have been licenced and these are now vying for pole position in the treatment algorithm. One must exercise caution however until the long term effects of any new medicines are known. PMID- 27253973 TI - Biotic Resistance to an Alien Amphibian: Larval Competition between Japanese Frogs and Invasive Cane Toads. AB - Understanding negative effects of native species on introduced taxa may suggest novel ways to control the invasive species by enhancing such effects. Previous studies have reported that the larvae of invasive cane toads (Rhinella marina) are suppressed by competition with the larvae of native anurans in Australia, but not in North America. We conducted laboratory trials to measure the effect of exposure to the larvae of Japanese frogs (Microhyla ornata, Fejervarya sakishimensis, Rhacophorus owstoni) on rates of survival, growth and development of cane toad tadpoles in Ishigaki Island, in southern Japan. Survival rates were not affected by native species, but competition with Dicroglossids and Rhacophorids (but not Microhylids) strongly reduced rates of growth and development in the tadpoles of cane toads. Dicroglossid tadpoles also reduced the body condition to toad tadpoles in addition to effects on SVL and mass. Encouraging populations of native frogs in toad-invaded areas of Japan thus may help to reduce the numbers of invasive cane toads. PMID- 27253974 TI - An Estimation of Mortality Risks among People Living with HIV in Karnataka State, India: Learnings from an Intensive HIV/AIDS Care and Support Programme. AB - BACKGROUND: In Indian context, limited attempts have been made to estimate the mortality risks among people living with HIV (PLHIV). We estimated the rates of mortality among PLHIV covered under an integrated HIV-prevention cum care and support programme implemented in Karnataka state, India, and attempted to identify the key programme components associated with the higher likelihood of their survival. METHODS: Retrospective programme data of 55,801 PLHIV registered with the Samastha programme implemented in Karnataka state during 2006-11 was used. Kaplan-Meier survival methods were used to estimate the ten years expected survival probabilities and Cox-proportional hazard model was used to examine the factors associated with risk of mortality among PLHIV. We also calculated mortality rates (per 1000 person-year) across selected demographic and clinical parameters. RESULTS: Of the total PLHIV registered with the programme, about nine percent died within the 5-years of programme period with an overall death rate of 38 per 1000 person-years. The mortality rate was higher among males, aged 18 and above, among illiterates, and those residing in rural areas. While the presence of co-infections such as Tuberculosis leads to higher mortality rate, adherence to ART was significantly associated with reduction in overall death rate. Cox proportional hazard model revealed that increase in CD4 cell counts and exposure to intensive care and support programme for at least two years can bring significant reduction in risk of death among PLHIV [(hazard ratio: 0.234; CI: 0.211-0.260) & (hazard ratio: 0.062; CI: 0.054-0.071), respectively] even after adjusting the effect of other socio-demographic, economic and health related confounders. CONCLUSION: Study confirms that while residing in rural areas and presence of co-infection significantly increases the mortality risk among PLHIV, adherence to ART and improvement in CD4 counts led to significant reduction in their mortality risk. Longer exposure to the intervention contributed significantly to reduce mortality among PLHIV. PMID- 27253987 TI - Improving the patient experience in the delivery of high quality surgical care and health outcomes. PMID- 27253975 TI - Bacteria with Phosphate Solubilizing Capacity Alter Mycorrhizal Fungal Growth Both Inside and Outside the Root and in the Presence of Native Microbial Communities. AB - Arbuscular mycorrhizal fungi (AMF) and phosphate solubilizing Pseudomonas bacteria (PSB) could potentially interact synergistically because PSB solubilize phosphate into a form that AMF can absorb and transport to the plant. However, very little is known about the interactions between these two groups of microorganisms and how they influence the growth of each other. We tested whether different strains of bacteria, that have the capacity to solubilize phosphate, are able to grow along AMF hyphae and differentially influence the growth of AMF both outside the roots of carrot in in vitro conditions and inside the roots of potato in the presence of a microbial community. We found strong effects of AMF on the growth of the different bacterial strains. Different bacterial strains also had very strong effects on the growth of AMF extraradical hyphae outside the roots of carrot and on colonization of potato roots by AMF. The differential effects on colonization occurred in the presence of a microbial community. Our results show that these two important groups of rhizosphere microorganisms indeed interact with each other. Such interactions could potentially lead to synergistic effects between the two groups but this could depend on whether the bacteria truly solubilize phosphate in the rhizosphere in the presence of microbial communities. PMID- 27253988 TI - IgG4 but no IgG1 antibody production after intralymphatic immunotherapy with recombinant MAT-Feld1 in human. AB - Allergy immunotherapy (AIT) mediates protection against allergen exposure in part due to allergen-specific antibodies. While immunization typically stimulated IgG1 and IgG2, AIT is often associated with production of IgG4. Here, twenty cat dander-sensitized patients were randomized to receive three injections of intralymphatic immunotherapy (ILIT) with MAT-Feld1 adsorbed to aluminum hydroxide or just aluminum hydroxide (placebo) in a double-blind setting (ClinicalTrials.gov NCT00718679). Whereas the clinical data, showing benefit of Mat-Feld1 ILIT was published in 2012 (Senti et al., J Allergy Clin Immunol, vol 129(5):1290-1296), the current study investigated the cat allergen-specific antibody responses. Blood was drawn prior to ILIT, as well as 1, 3, and 12 months after first ILIT. The sera were analyzed to characterize all IgG subclasses and IgE antibody responses. ILIT with MAT-Feld1 elicited high levels of total IgG that were maintained for at least 12 months. Interestingly, a strong increase in IgG4 and some increase in IgG2 were observed throughout the study, while production of cat-specific IgG1 and IgG3 was not stimulated by MAT-Feld1 ILIT. The IgE levels remained constant. PMID- 27253989 TI - A Selective and Slowly Reversible Inhibitor of l-Type Amino Acid Transporter 1 (LAT1) Potentiates Antiproliferative Drug Efficacy in Cancer Cells. AB - The l-type amino acid transporter 1 (LAT1) is a transmembrane protein carrying bulky and neutral amino acids into cells. LAT1 is overexpressed in several types of tumors, and its inhibition can result in reduced cancer cell growth. However, known LAT1 inhibitors lack selectivity over other transporters. In the present study, we designed and synthesized a novel selective LAT1 inhibitor (1), which inhibited the uptake of LAT1 substrate, l-leucin as well as cell growth. It also significantly potentiated the efficacy of bestatin and cisplatin even at low concentrations (25 MUM). Inhibition was slowly reversible, as the inhibitor was able to be detached from the cell surface and blood-brain barrier. Moreover, the inhibitor was metabolically stable and selective toward LAT1. Since the inhibitor was readily accumulated into the prostate after intraperitoneal injection to the healthy mice, this compound may be a promising agent or adjuvant especially for the treatment of prostate cancer. PMID- 27253990 TI - Correction: The Cotton WRKY Gene GhWRKY41 Positively Regulates Salt and Drought Stress Tolerance in Transgenic Nicotiana benthamiana. AB - [This corrects the article DOI: 10.1371/journal.pone.0143022.]. PMID- 27253991 TI - Assessing ecotoxicity of biomining effluents in stream ecosystems by in situ invertebrate bioassays: A case study in Talvivaara, Finland. AB - Mining of sulfide-rich pyritic ores produces acid mine drainage waters and has induced major ecological problems in aquatic ecosystems worldwide. Biomining utilizes microbes to extract metals from the ore, and it has been suggested as a new sustainable way to produce metals. However, little is known of the potential ecotoxicological effects of biomining. In the present study, biomining impacts were assessed using survival and behavioral responses of aquatic macroinvertebrates at in situ exposures in streams. The authors used an impedance conversion technique to measure quantitatively in situ behavioral responses of larvae of the regionally common mayfly, Heptagenia dalecarlica, to discharges from the Talvivaara mine (Sotkamo, Northern Finland), which uses a biomining technique. Behavioral responses measured in 3 mine-impacted streams were compared with those measured in 3 reference streams. In addition, 3-d survival of the mayfly larvae and the oligochaete Lumbriculus variegatus was measured in the study sites. Biomining impacts on stream water quality included increased concentrations of sulfur, sulfate, and metals, especially manganese, cadmium, zinc, sodium, and calcium. Survival of the invertebrates in the short term was not affected by the mine effluents. In contrast, apparent behavioral changes in mayfly larvae were detected, but these responses were not consistent among sites, which may reflect differing natural water chemistry of the study sites. Environ Toxicol Chem 2017;36:147-155. (c) 2016 SETAC. PMID- 27253992 TI - Role of the BrafV637E mutation in hepatocarcinogenesis induced by treatment with diethylnitrosamine in neonatal B6C3F1 mice. AB - The BrafV637E mutation is frequently reported in mouse hepatic tumors, depending on the mouse strain, and corresponds to the human BrafV600E mutation. In this study, we detected the BrafV637E mutation by whole-exome analysis in 4/4 hepatic tumors induced by neonatal treatment with diethylnitrosamine (DEN) in male B6C3F1 mice. We also detected the BrafV637E mutation in 54/63 (85.7%) hepatic lesions, including microscopic foci and grossly visible tumors, by PCR-direct sequencing. Although the mutation was detected in 5/7 (71.4%) hepatic tumors induced by neonatal DEN treatment followed by repeated CCl4 administration, it was not detected in 24 tumors induced by CCl4 treatment without DEN or in eight spontaneous lesions in B6C3F1 mice, suggesting that the mutation is induced by the genotoxic action of DEN. The DEN-induced tumors exhibited hyperphosphorylation of ERK1 and Akt, suggesting that the BrafV637E mutation might activate the MAPK and Akt pathways. Moreover, the DEN-induced tumors overexpressed mRNAs for the oncogene-induced senescence (OIS) markers such as p15Ink4b and p19Arf as well as pro-survival/pro-proliferative cytokines/chemokines such as complement C5/C5a, ICAM-1, IL-1 receptor antagonist and CXCL9, suggesting that the BrafV637E mutation influences the expression of genes involved in either OIS or cellular growth/survival. Liver-specific expression of mutated Braf under control of the albumin enhancer/promoter resulted in an enlarged liver that consisted entirely of small basophilic hepatocytes resembling DEN-induced preneoplastic hepatocytes with ERK1/Akt hyperphosphorylation and C5/C5a overexpression. These results indicate that the BrafV637E mutation induces hepatocytic changes in DEN-induced hepatic tumors. (c) 2016 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc. PMID- 27253993 TI - Family Presence during Resuscitation: A Qualitative Analysis from a National Multicenter Randomized Clinical Trial. AB - BACKGROUND: The themes of qualitative assessments that characterize the experience of family members offered the choice of observing cardiopulmonary resuscitation (CPR) of a loved one have not been formally identified. METHODS AND FINDINGS: In the context of a multicenter randomized clinical trial offering family members the choice of observing CPR of a patient with sudden cardiac arrest, a qualitative analysis, with a sequential explanatory design, was conducted. The aim of the study was to understand family members' experience during CPR. All participants were interviewed by phone at home three months after cardiac arrest. Saturation was reached after analysis of 30 interviews of a randomly selected sample of 75 family members included in the trial. Four themes were identified: 1- choosing to be actively involved in the resuscitation; 2- communication between the relative and the emergency care team; 3- perception of the reality of the death, promoting acceptance of the loss; 4- experience and reactions of the relatives who did or did not witness the CPR, describing their feelings. Twelve sub-themes further defining these four themes were identified. Transferability of our findings should take into account the country-specific medical system. CONCLUSIONS: Family presence can help to ameliorate the pain of the death, through the feeling of having helped to support the patient during the passage from life to death and of having participated in this important moment. Our results showed the central role of communication between the family and the emergency care team in facilitating the acceptance of the reality of death. PMID- 27253994 TI - Synthetic High-Density Lipoprotein (sHDL) Inhibits Steroid Production in HAC15 Adrenal Cells. AB - High density lipoprotein (HDL) transported cholesterol represents one of the sources of substrate for adrenal steroid production. Synthetic HDL (sHDL) particles represent a new therapeutic option to reduce atherosclerotic plaque burden by increasing cholesterol efflux from macrophage cells. The effects of the sHDL particles on steroidogenic cells have not been explored. sHDL, specifically ETC-642, was studied in HAC15 adrenocortical cells. Cells were treated with sHDL, forskolin, 22R-hydroxycholesterol, or pregnenolone. Experiments included time and concentration response curves, followed by steroid assay. Quantitative real-time RT-PCR was used to study mRNA of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, lanosterol 14-alpha-methylase, cholesterol side-chain cleavage enzyme, and steroid acute regulatory protein. Cholesterol assay was performed using cell culture media and cell lipid extracts from a dose response experiment. sHDL significantly inhibited production of cortisol. Inhibition occurred in a concentration- and time-dependent manner and in a concentration range of 3MUM 50MUM. Forskolin (10MUM) stimulated cortisol production was also inhibited. Incubation with 22R-hydroxycholesterol (10MUM) and pregnenolone (10MUM) increased cortisol production, which was unaffected by sHDL treatment. sHDL increased transcript levels for the rate-limiting cholesterol biosynthetic enzyme, 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase. Extracellular cholesterol assayed in culture media showed a positive correlation with increasing concentration of sHDL, whereas intracellular cholesterol decreased after treatment with sHDL. The current study suggests that sHDL inhibits HAC15 adrenal cell steroid production by efflux of cholesterol, leading to an overall decrease in steroid production and an adaptive rise in adrenal cholesterol biosynthesis. PMID- 27253995 TI - Adult-Onset Deletion of beta-Catenin in (10kb)Dmp1-Expressing Cells Prevents Intermittent PTH-Induced Bone Gain. AB - beta-Catenin (betacat) is a major downstream signaling node in canonical Wingless related integration site (Wnt) signaling pathway, and its activity is crucial for canonical Wnt signal transduction. Wnt signaling has recently been implicated in the osteo-anabolic response to PTH, a potent calcium-regulating factor. We investigated whether betacat is essential for the anabolic action of intermittent PTH by generating male mice with adult-onset deletion of betacat in a subpopulation of bone cells (osteocytes and late-stage osteoblasts), treating them with an anabolic regimen of PTH, and measuring the skeletal responses. Male (10kb)Dmp1-CreERt2 transgenic mice that also harbored floxed loss-of-function betacat alleles (betacat(f/f)) were induced for Cre activity using tamoxifen, then injected daily with human PTH 1-34 (30 MUg/kg) or vehicle for 5 weeks. Mice in which betacat was deleted showed either total lack of bone mineral density (BMD) gain, or BMD loss, and did not respond to PTH treatment. However, bone mass measurements in the trabecular compartment of the femur and spine revealed PTH induced bone gain whether betacat was deleted or not. PTH-stimulated increases in periosteal and cancellous bone formation rates were not impaired by betacat deletion, but resorption markers and cortical porosity were significantly increased in induced mice, particularly induced mice treated with PTH. These results suggest that betacat is required for net-positive BMD effects of PTH therapy but that the anabolic effects per se of PTH treatment might not require osteocytic/osteoblastic betacat. PMID- 27253996 TI - Rescue of Isolated GH Deficiency Type II (IGHD II) via Pharmacologic Modulation of GH-1 Splicing. AB - Isolated GH deficiency (IGHD) type II, the autosomal dominant form of GHD, is mainly caused by mutations that affect splicing of GH-1. When misspliced RNA is translated, it produces a toxic 17.5-kDa GH isoform that reduces the accumulation and secretion of wild-type-human GH (wt-hGH). Usually, isolated GHD type II patients are treated with daily injections of recombinant human GH in order to maintain normal growth. However, this type of replacement therapy does not prevent toxic effects of the 17.5-kDa GH isoform on the pituitary gland, which can eventually lead to other hormonal deficiencies. Here, we tested the possibility to restore the constitutive splicing pattern of GH-1 by using butyrate, a drug that mainly acts as histone deacetylase inhibitor. To this aim, wt-hGH and/or different hGH-splice site mutants (GH-IVS3+2, GH-IVS3+6, and GH ISE+28) were transfected in rat pituitary cells expressing human GHRH receptor (GHRHR) (GC-GHRHR). Upon butyrate treatment, GC-GHRHR cells coexpressing wt-hGH and each of the mutants displayed increased GH transcript level, intracellular GH content, and GH secretion when compared with the corresponding untreated condition. The effect of butyrate was most likely mediated by the alternative splicing factor/splicing factor 2. Overexpression of alternative ASF/SF2 in the same experimental setting, indeed, promoted the amount of full-length transcripts thus increasing synthesis and secretion of the 22-kDa GH isoform. In conclusion, our results support the hypothesis that modulation of GH-1 splicing pattern to increase the 22-kDa GH isoform levels can be clinically beneficial and hence a crucial challenge in GHD research. PMID- 27253997 TI - Clock Gene Bmal1 Modulates Human Cartilage Gene Expression by Crosstalk With Sirt1. AB - The critical regulation of the peripheral circadian gene implicated in osteoarthritis (OA) has been recently recognized; however, the causative role and clinical potential of the peripheral circadian rhythm attributable to such effects remain elusive. The purpose of this study was to elucidate the role of a circadian gene Bmal1 in human cartilage and pathophysiology of osteoarthritis. In our present study, the mRNA and protein levels of circadian rhythm genes, including nicotinamide adenine dinucleotide oxidase (NAD(+)) and sirtuin 1 (Sirt1), in human knee articular cartilage were determined. In OA cartilage, the levels of both Bmal1 and NAD(+) decreased significantly, which resulted in the inhibition of nicotinamide phosphoribosyltransferase activity and Sirt1 expression. Furthermore, the knockdown of Bmal1 was sufficient to decrease the level of NAD(+) and aggravate OA-like gene expression changes under the stimulation of IL-1beta. The overexpression of Bmal1 relieved the alteration induced by IL-1beta, which was consistent with the effect of the inhibition of Rev-Erbalpha (known as NR1D1, nuclear receptor subfamily 1, group D). On the other hand, the transfection of Sirt1 small interfering RNA not only resulted in a reduction of the protein expression of Bmal1 and a moderate increase of period 2 (per2) and Rev-Erbalpha but also further exacerbated the survival of cells and the expression of cartilage matrix-degrading enzymes induced by IL-1beta. Overexpression of Sirt1 restored the metabolic imbalance of chondrocytes caused by IL-1beta. These observations suggest that Bmal1 is a key clock gene to involve in cartilage homeostasis mediated through sirt1 and that manipulating circadian rhythm gene expression implicates an innovative strategy to develop novel therapeutic agents against cartilage diseases. PMID- 27253999 TI - Cardiac Tissue Injury and Remodeling Is Dependent Upon MR Regulation of Activation Pathways in Cardiac Tissue Macrophages. AB - Macrophage mineralocorticoid receptor (MR) signaling is an important mediator of cardiac tissue inflammation and fibrosis. The goal of the present study was to determine the cellular mechanisms of MR signaling in macrophages that promote cardiac tissue injury and remodeling. We sought to identify specific markers of MR signaling in isolated tissue macrophages (cardiac, aortic) vs splenic mononuclear cells from wild-type and myeloid MR-null mice given vehicle/salt or deoxycorticosterone (DOC)/salt for 8 weeks. Cardiac tissue fibrosis in response to 8 weeks of DOC/salt treatment was found in the hearts from wild-type but not myeloid MR-null mice. This was associated with an increased expression of the profibrotic markers TGF-beta1 and matrix metalloproteinase-12 and type 1 inflammatory markers TNFalpha and chemokine (C-X-C motif) ligand-9 in cardiac macrophages. Differential expression of immunomodulatory M2-like markers (eg, arginase-1, macrophage scavenger receptor 1) was dependent on the tissue location of wild-type and MR-null macrophages. Finally, intact MR signaling is required for the phosphorylation of c-Jun NH2-terminal kinase in response to a proinflammatory stimulus in bone marrow monocytes/macrophages in culture. These data suggest that the activation of the c-Jun NH2-terminal kinase pathway in macrophages after a tissue injury and inflammatory stimuli in the DOC/salt model is MR dependent and regulates the transcription of downstream profibrotic factors, which may represent potential therapeutic targets in heart failure patients. PMID- 27253998 TI - Thyroid Hormone Receptor-beta (TRbeta) Mediates Runt-Related Transcription Factor 2 (Runx2) Expression in Thyroid Cancer Cells: A Novel Signaling Pathway in Thyroid Cancer. AB - Dysregulation of the thyroid hormone receptor (TR)beta is common in human cancers. Restoration of functional TRbeta delays tumor progression in models of thyroid and breast cancers implicating TRbeta as a tumor suppressor. Conversely, aberrant expression of the runt-related transcription factor 2 (Runx2) is established in the progression and metastasis of thyroid, breast, and other cancers. Silencing of Runx2 diminishes tumor invasive characteristics. With TRbeta as a tumor suppressor and Runx2 as a tumor promoter, a compelling question is whether there is a functional relationship between these regulatory factors in thyroid tumorigenesis. Here, we demonstrated that these proteins are reciprocally expressed in normal and malignant thyroid cells; TRbeta is high in normal cells, and Runx2 is high in malignant cells. T3 induced a time- and concentration dependent decrease in Runx2 expression. Silencing of TRbeta by small interfering RNA knockdown resulted in a corresponding increase in Runx2 and Runx2-regulated genes, indicating that TRbeta levels directly impact Runx2 expression and associated epithelial to mesenchymal transition molecules. TRbeta specifically bound to 3 putative thyroid hormone-response element motifs within the Runx2-P1 promoter ((-)105/(+)133) as detected by EMSA and chromatin immunoprecipitation. TRbeta suppressed Runx2 transcriptional activities, thus confirming TRbeta regulation of Runx2 at functional thyroid hormone-response elements. Significantly, these findings indicate that a ratio of the tumor-suppressor TRbeta and tumor-promoting Runx2 may reflect tumor aggression and serve as biomarkers in biopsy tissues. The discovery of this TRbeta-Runx2 signaling supports the emerging role of TRbeta as a tumor suppressor and reveals a novel pathway for intervention. PMID- 27254000 TI - Morphology, Biochemistry, and Pathophysiology of MENX-Related Pheochromocytoma Recapitulate the Clinical Features. AB - Pheochromocytomas (PCCs) are tumors arising from neural crest-derived chromaffin cells. There are currently few animal models of PCC that recapitulate the key features of human tumors. Because such models may be useful for investigations of molecular pathomechanisms and development of novel therapeutic interventions, we characterized a spontaneous animal model (multiple endocrine neoplasia [MENX] rats) that develops endogenous PCCs with complete penetrance. Urine was longitudinally collected from wild-type (wt) and MENX-affected (mutant) rats and outputs of catecholamines and their O-methylated metabolites determined by mass spectrometry. Adrenal catecholamine contents, cellular ultrastructure, and expression of phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine, were also determined in wt and mutant rats. Blood pressure was longitudinally measured and end-organ pathology assessed. Compared with wt rats, mutant animals showed age-dependent increases in urinary outputs of norepinephrine (P = .0079) and normetanephrine (P = .0014) that correlated in time with development of tumor nodules, increases in blood pressure, and development of hypertension-related end-organ pathology. Development of tumor nodules, which lacked expression of N-methyltransferase, occurred on a background of adrenal medullary morphological and biochemical changes occurring as early as 1 month of age and involving increased adrenal medullary concentrations of dense cored vesicles, tissue contents of both norepinephrine and epinephrine, and urinary outputs of metanephrine, the metabolite of epinephrine. Taken together, MENX-affected rats share several biochemical and pathophysiological features with PCC patients. This model thus provides a suitable platform to study the pathogenesis of PCC for preclinical translational studies aimed at the development of novel therapies for aggressive forms of human tumors. PMID- 27254001 TI - Glucocorticoids Inhibit CRH/AVP-Evoked Bursting Activity of Male Murine Anterior Pituitary Corticotrophs. AB - Corticotroph cells from the anterior pituitary are an integral component of the hypothalamic-pituitary-adrenal (HPA) axis, which governs the neuroendocrine response to stress. Corticotrophs are electrically excitable and fire spontaneous single-spike action potentials and also display secretagogue-induced bursting behavior. The HPA axis function is dependent on effective negative feedback in which elevated plasma glucocorticoids result in inhibition at the level of both the pituitary and the hypothalamus. In this study, we have used an electrophysiological approach coupled with mathematical modeling to investigate the regulation of spontaneous and CRH/arginine vasopressin-induced activity of corticotrophs by glucocorticoids. We reveal that pretreatment of corticotrophs with 100 nM corticosterone (CORT; 90 and 150 min) reduces spontaneous activity and prevents a transition from spiking to bursting after CRH/arginine vasopressin stimulation. In addition, previous studies have identified a role for large conductance calcium- and voltage-activated potassium (BK) channels in the generation of secretagogue-induced bursting in corticotrophs. Using the dynamic clamp technique, we demonstrated that CRH-induced bursting can be switched to spiking by subtracting a fast BK current, whereas the addition of a fast BK current can induce bursting in CORT-treated cells. In addition, recordings from BK knockout mice (BK(-/-)) revealed that CORT can also inhibit excitability through BK-independent mechanisms to control spike frequency. Thus, we have established that glucocorticoids can modulate multiple properties of corticotroph electrical excitability through both BK-dependent and BK-independent mechanisms. PMID- 27254002 TI - Sex Differences in the Impact of Shift Work Schedules on Pathological Outcomes in an Animal Model of Ischemic Stroke. AB - Circadian clock desynchronization has been implicated in the pathophysiology of cardiovascular disease and related risk factors (eg, obesity, diabetes). Thus, we examined the extent to which circadian desynchronization exacerbates ischemic stroke outcomes and whether its detrimental effects on stroke severity and functional impairments are further modified by biological sex. Circadian entrainment of activity rhythms in all male and female rats was observed during exposure to a fixed light-dark (LD) 12:12 cycle but was severely disrupted when this LD cycle was routinely shifted (12 h advance/5 d) for approximately 7 weeks. In contrast to the regular estrous cycles in fixed LD animals, cyclicity was abolished and persistent estrus was evident in all shifted LD females. The disruption of estrous cyclicity in shifted LD females was associated with a significant increase in serum estradiol levels relative to that observed in fixed LD controls. Circadian rhythm disruption exacerbated stroke outcomes in both shifted LD male and female rats and further amplified sex differences in stroke impairments. In males, but not females, circadian disruption after exposure to the shifted LD cycle was marked by high rates of mortality. In surviving females, circadian desynchronization after exposure to shifted LD cycles produced significant increases in stroke-induced infarct volume and sensorimotor deficits with corresponding decreases in serum IGF-1 levels. These results suggest that circadian rhythm disruption associated with shift work schedules or the irregular nature of our everyday work and/or social environments may interact with other nonmodifiable risk factors such as biological sex to modulate the pathological effects of stroke. PMID- 27254003 TI - MCT8 Deficiency in Male Mice Mitigates the Phenotypic Abnormalities Associated With the Absence of a Functional Type 3 Deiodinase. AB - Mice deficient in the type 3 deiodinase (D3KO mice) manifest impaired clearance of thyroid hormone (TH), leading to elevated levels of TH action during development. This alteration causes reduced neonatal viability, growth retardation, and central hypothyroidism. Here we examined how these phenotypes are affected by a deficiency in the monocarboxylate transporter 8 (MCT8), which is a major contributor to the transport of the active thyroid hormone, T3, into the cell. MCT8 deficiency eliminated the neonatal lethality of type 3 deiodinase (D3)-deficient mice and significantly ameliorated their growth retardation. Double-mutant newborn mice exhibited similar peripheral thyrotoxicosis and increased brain expression of T3-dependent genes as mice with D3 deficiency only. Later in neonatal life and adulthood, double-mutant mice manifested central and peripheral TH status similar to mice with single MCT8 deficiency, with low serum T4, elevated serum TSH and T3, and decreased T3-dependent gene expression in the hypothalamus. In double-mutant adult mice, both thyroid gland size and the hypothyroidism-induced rise in TSH were greater than those in mice with single D3 deficiency but less than those in mice with MCT8 deficiency alone. Our results demonstrate that the marked phenotypic abnormalities observed in the D3-deficient mouse, including perinatal mortality, growth retardation, and central hypothyroidism in adult animals, require expression of MCT8, confirming the interdependent relationship between the TH transport into cells and the deiodination processes. PMID- 27254004 TI - Female Mice Lacking Estrogen Receptor-alpha in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass. AB - Estrogens are important regulators of bone mass and their effects are mainly mediated via estrogen receptor (ER)alpha. Central ERalpha exerts an inhibitory role on bone mass. ERalpha is highly expressed in the arcuate (ARC) and the ventromedial (VMN) nuclei in the hypothalamus. To test whether ERalpha in proopiomelanocortin (POMC) neurons, located in ARC, is involved in the regulation of bone mass, we used mice lacking ERalpha expression specifically in POMC neurons (POMC-ERalpha(-/-)). Female POMC-ERalpha(-/-) and control mice were ovariectomized (OVX) and treated with vehicle or estradiol (0.5 MUg/d) for 6 weeks. As expected, estradiol treatment increased the cortical bone thickness in femur, the cortical bone mechanical strength in tibia and the trabecular bone volume fraction in both femur and vertebrae in OVX control mice. Importantly, the estrogenic responses were substantially increased in OVX POMC-ERalpha(-/-) mice compared with the estrogenic responses in OVX control mice for cortical bone thickness (+126 +/- 34%, P < .01) and mechanical strength (+193 +/- 38%, P < .01). To test whether ERalpha in VMN is involved in the regulation of bone mass, ERalpha was silenced using an adeno-associated viral vector. Silencing of ERalpha in hypothalamic VMN resulted in unchanged bone mass. In conclusion, mice lacking ERalpha in POMC neurons display enhanced estrogenic response on cortical bone mass and mechanical strength. We propose that the balance between inhibitory effects of central ERalpha activity in hypothalamic POMC neurons in ARC and stimulatory peripheral ERalpha-mediated effects in bone determines cortical bone mass in female mice. PMID- 27254005 TI - Evidence for Ligand-Independent Activation of Hippocampal Estrogen Receptor-alpha by IGF-1 in Hippocampus of Ovariectomized Rats. AB - In the absence of ovarian estrogens, increased levels of estrogen receptor (ER)alpha in the hippocampus are associated with improvements in cognition. In vitro evidence indicates that under conditions of low estrogen, growth factors, including Insulin-Like Growth Factor 1 (IGF-1), can activate ERalpha and regulate ERalpha-mediated transcription through mechanisms that likely involve modification of phosphorylation sites on the receptor. The goal of the current work was to investigate a role for IGF-1 in ligand-independent activation of ERalpha in the hippocampus of female rats. Ovariectomized rats received a single intracerebroventricular infusion of IGF-1 and hippocampi were collected 1 or 24 hours later. After 1 h, IGF-1 increased hippocampal levels of phosphorylated ERalpha at serine 118 (S118) as revealed by Western blotting. Coimmunoprecipitation revealed that at 1 hour after infusion, IGF-1 increased association between ERalpha and steroid receptor coactivator 1, a histone acetyltransferase that increases transcriptional activity of phosphorylated ERalpha. IGF-1 infusion increased levels of the ERalpha-regulated proteins ERalpha, choline acetyltransferase, and brain-derived neurotrophic factor in the hippocampus 24 hours after infusion. Results indicate that IGF-1 activates ERalpha in ligand-independent manner in the hippocampus via phosphorylation at S118 resulting in increased association of ERalpha with steroid receptor coactivator 1 and elevation of ER-regulated proteins. To our knowledge, these data are the first in vivo evidence of ligand-independent actions of ERalpha and provide a mechanism by which ERalpha can impact memory in the absence of ovarian estrogens. PMID- 27254007 TI - Scylla and Charybdis: The MCAT, USMLE, and Degrees of Freedom in Undergraduate Medical Education. AB - In recent years, medical educators have been making meaningful attempts to rethink how premedical students are prepared for medical school, and how medical students are prepared for residency. Among the many challenges to redesigning premedical and medical school curricula, one that stands out is the constraint imposed by our current methods of assessing aptitude, particularly our use of the Medical College Admissions Test (MCAT) and the United States Medical Licensing Examination (USMLE). For much of the past century, medical school and residency admissions committees have relied heavily on MCAT and USMLE scores to evaluate and rank candidates to their programs. These high-stakes exams determine to a large extent what is taught, and what is stressed, in preparation for and during medical school-despite the fact that scores have limited ability to predict future success in clinical medicine or biomedical research. Additionally, evidence indicates that students from disadvantaged and minority backgrounds do not fare as well on these exams and, as a result, may be disproportionately excluded from the medical profession. While medical school admissions committees have made limited incremental gains in holistic review, residency programs appear to be increasingly focused on USMLE Step scores and veering away from the spirit of holistic review. The authors propose that substantive change will remain slow in coming unless members of the medical education community radically rethink how we report scores from these exams, and how we use them in our selection of future medical students and residents. PMID- 27254006 TI - mTORC1 Signaling Contributes to Drinking But Not Blood Pressure Responses to Brain Angiotensin II. AB - Mechanistic target of rapamycin complex 1 (mTORC1) is a molecular node that couples extracellular cues to a wide range of cellular events controlling various physiological processes. Here, we identified mTORC1 signaling as a critical mediator of angiotensin II (Ang II) action in the brain. In neuronal GT1-7 cells, we show that Ang II stimulates neuronal mTORC1 signaling in an Ang II type 1 receptor-dependent manner. In mice, a single intracerebroventricular (ICV) injection or chronic sc infusion of Ang II activated mTORC1 signaling in the subfornical organ, a critical brain region in cardiovascular control and fluid balance. Moreover, transgenic sRA mice with brain-specific overproduction of Ang II displayed increased mTORC1 signaling in the subfornical organ. To test the functional role of brain mTORC1 in mediating the action of Ang II, we examined the consequence of mTORC1 inhibition with rapamycin on Ang II-induced increase in water intake and arterial pressure. ICV pretreatment with rapamycin blocked ICV Ang II-mediated increases in the frequency, duration, and amount of water intake but did not interfere with the pressor response evoked by Ang II. In addition, ICV delivery of rapamycin significantly reduced polydipsia, but not hypertension, of sRA mice. These results demonstrate that mTORC1 is a novel downstream pathway of Ang II type 1 receptor signaling in the brain and selectively mediates the effect of Ang II on drinking behavior. PMID- 27254009 TI - Post-tenure Review at U.S. Medical Schools. AB - PURPOSE: To assess post-tenure review policies at U.S. medical schools by examining how prevalent post-tenure review is, what models of post-tenure review are employed, and what outcomes result from post-tenure review processes. METHOD: In late 2014, a Web-based survey was sent to the associate dean for faculty affairs (or equivalent) at each U.S. medical school accredited by the Liaison Committee on Medical Education (N = 141). The survey addressed elements of post tenure review policies, including whether a policy was in place, the frequency of the review, and the review outcomes. Descriptive statistics were calculated. RESULTS: Of the 94 responding schools with a tenure system, 39 (41%) had an established post-tenure review policy. Although these policies showed great variability across schools in duration, having been in place from 1 to 50 years, 12 (31%) were established within the last 5 years. The outcomes of post-tenure review also varied. Superior performance ratings generally resulted in notations in the faculty member's personnel file and notifications to school leadership. Conversely, when a faculty member received an unsatisfactory rating, a remediation or development plan was sometimes required. CONCLUSIONS: At least 40% of medical schools with a tenure system have post-tenure review, and it is becoming more common. These findings about the prevalence and use of post-tenure review across institutions can assist medical school leaders as they strive to shape policies to facilitate faculty engagement and productivity. They also can provide the foundation for future evaluative studies on the effectiveness, outcomes, and impact of post-tenure review. PMID- 27254008 TI - How Women in Biomedical PhD Programs Manage Gender Consciousness as They Persist Toward Academic Research Careers. AB - PURPOSE: Women remain underrepresented as biomedical faculty and are more likely than white and Asian men to lose interest in faculty careers in graduate school. However, some women maintain interest in academic research careers during PhD training and are the most likely candidates for faculty positions. This study explored how these women described and interpreted gender issues at early stages in their training. METHOD: Annual interviews from 2009 to 2014 with 22 female PhD students aspiring to research faculty careers were analyzed using an iterative, content analysis approach rooted in the interview data. Focusing on career intentions and experiences with gender, race, and ethnicity, authors arrived at 11 themes which describe a range of gendered experiences and strategies. RESULTS: Of the 22 women, 19 (86%) acknowl edged systemic gender inequities in science and/or reported instances of bias, while 15 of them also said they had not yet experienced unequal treatment. All 22 described using at least one "gender explicit strategy," where they based decisions on gender or in response to perceived biases. "Gender-agnostic strategies" emerged for 12 (55%) who doubted that gender will affect their career. CONCLUSIONS: Findings show that women biomedical PhD students continue to face conditions that can lead to unequal treatment; gender biases continue to persist. Students displayed a range of perceptions and strategies in response to these conditions at this early training stage. Following these students over time will determine whether these or other strategies are required and sufficient to enable persistence toward academic careers. PMID- 27254010 TI - Systems-Oriented Workplace Learning Experiences for Early Learners: Three Models. AB - PURPOSE: Early workplace learning experiences may be effective for learning systems-based practice. This study explores systems-oriented workplace learning experiences (SOWLEs) for early learners to suggest a framework for their development. METHOD: The authors used a two-phase qualitative case study design. In Phase 1 (spring 2014), they prepared case write-ups based on transcribed interviews from 10 SOWLE leaders at the authors' institution and, through comparative analysis of cases, identified three SOWLE models. In Phase 2 (summer 2014), studying seven 8-week SOWLE pilots, the authors used interview and observational data collected from the seven participating medical students, two pharmacy students, and site leaders to construct case write-ups of each pilot and to verify and elaborate the models. RESULTS: In Model 1, students performed specific patient care activities that addressed a system gap. Some site leaders helped students connect the activities to larger systems problems and potential improvements. In Model 2, students participated in predetermined systems improvement (SI) projects, gaining experience in the improvement process. Site leaders had experience in SI and often had significant roles in the projects. In Model 3, students worked with key stakeholders to develop a project and conduct a small test of change. They experienced most elements of an improvement cycle. Site leaders often had experience with SI and knew how to guide and support students' learning. CONCLUSIONS: Each model could offer systems-oriented learning opportunities provided that key elements are in place including site leaders facile in SI concepts and able to guide students in SOWLE activities. PMID- 27254011 TI - Professional Identity Formation and the Clinician-Scientist: A Paradigm for a Clinical Career Combining Two Distinct Disciplines. AB - The clinician-scientist role is critical to the future of health care, and in 2010, the Carnegie Report on Educating Physicians focused attention on the professional identity of practicing clinicians. Although limited in number, published studies on the topic suggest that professional identity is likely a critical factor that determines career sustainability. In contrast to clinicians with a singular focus on clinical practice, clinician-scientists combine two major disciplines, clinical medicine and scientific research, to bridge discovery and clinical care. Despite its importance to advancing medical practice, the clinician-scientist career faced a variety of threats, which have been identified recently by the 2014 National Institutes of Health Physician Scientist Workforce. Yet, professional identity development in this career pathway is poorly understood. This Perspective focuses on the challenges to the clinician scientist's professional identity and its development. First, the authors identify the particular challenges that arise from the different cultures of clinical care and science and the implications for clinician-scientist professional identity formation. Next, the authors synthesize insights about professional identity development within a dual-discipline career and apply their analysis to a discussion about the implications for clinician-scientist identity formation. Although not purposely developed to address identity formation, the authors highlight those elements within clinician-scientist training and career development programs that may implicitly support identity development. Finally, the authors highlight a need to identify empirically the elements that compose and determine clinician-scientist professional identity and the processes that shape its formation and sustainability. PMID- 27254012 TI - A Mixed-Methods Investigation of the Motivations, Goals, and Aspirations of Male and Female Academic Medical Faculty. AB - PURPOSE: Understanding the goals and aspirations of the physician-scientist workforce can inform policies to promote retention. The authors explored gender differences therein, given women's increasing representation. METHOD: In 2010 2011, the authors qualitatively analyzed interviews with 100 former recipients of National Institutes of Health career development awards and 28 of their mentors. They also compared survey responses of 1,267 clinician-investigators who received these awards from 2006 to 2009, using logistic regression to evaluate gender differences after adjusting for other characteristics. RESULTS: Interview participants described relatively consistent career goals, including scientific contribution and desire to positively affect lives through research, clinical care, and teaching. For many, the specific ways they sought to achieve and measure goal attainment evolved over time. Survey respondents endorsed a goal of publishing high-quality research with highest frequency (97.3%, no significant gender difference). Women were more likely to endorse the importance of balancing work and other activities (95.5% vs. 90.5%, P < .001). There were no significant gender differences in the importance of patient care (86.6%), teaching (71.6%), or publishing prolifically (64.9%). Men were more likely than women to consider salary (49.4% vs. 41.8%, P < .001), reputation (84.2% vs. 77.6%, P = .004), and leadership positions (38.9% vs. 34.3%, P = .03) important. CONCLUSIONS: In an elite research-oriented sample, gender differences in initial aspirations were generally limited. Gender differences in career outcomes in such groups are unlikely to exclusively result from different baseline aspirations. Goals appear to evolve in response to challenges experienced. PMID- 27254013 TI - Promoting the Development of Adaptive Expertise: Exploring a Simulation Model for Sharing a Diagnosis of Autism With Parents. AB - PURPOSE: To explore how a simulation model promoted the development of integrated competencies associated with adaptive expertise in senior health professions trainees as they learned to share a diagnosis of autism with parents. METHOD: A qualitative instrumental case study method was used at the University of Toronto in 2014 to explore what eight developmental pediatrics residents and two clinical psychology interns learned from participating in a simulation model designed to enable trainees to practice sharing a diagnosis of autism with parents. This model incorporated variability (three cases), active experimentation in a safe environment, and feedback from multiple perspectives (peers, faculty, standardized patients, and a parent). Field notes were collected, and semistructured interviews were conducted to explore what participants learned. Constant comparative analysis was used to identify themes iteratively. Team analysis continued until a stable thematic structure was developed and applied to the entire data set. RESULTS: Four themes were identified. Three themes described how participating in the simulation model changed residents' and interns' approaches to sharing a diagnosis of autism with parents from using a structured, scripted framework to share the diagnosis; to being flexible within the structured framework; and, finally, to being attentive and responsive to parents by adapting and creating new approaches for sharing the diagnosis. The fourth theme described how the multiple perspectives in the simulation model prompted learners to develop adaptive approaches. CONCLUSIONS: This simulation model helped residents and interns move beyond use of a structured, scripted communication framework toward development of adaptive expertise. PMID- 27254014 TI - The Predictive Validity of the National Board of Osteopathic Medical Examiners' COMLEX-USA Examinations With Regard to Outcomes on American Board of Family Medicine Examinations. AB - PURPOSE: To examine the predictive validity of the National Board of Osteopathic Medical Examiners' Comprehensive Osteopathic Medical Licensing Examination of the United States of America (COMLEX-USA) series with regard to the American Board of Family Medicine's (ABFM's) In-Training Examination (ITE) and Maintenance of Certification for Family Physicians (MC-FP) Examination. METHOD: A repeated measures design was employed, using test scores across seven levels of training for 1,023 DOs who took the MC-FP for the first time between April 2012 and November 2014 and for whom the ABFM had ITE scores for each of their residency years. Pearson and disattenuated correlations were calculated; Fisher r to z transformation was performed; and sensitivity, specificity, and positive and negative predictive values for the COMLEX-USA Level 2-Cognitive Evaluation (CE) with regard to the MC-FP were computed. RESULTS: The Pearson and disattenuated correlations ranged from 0.55 to 0.69 and from 0.61 to 0.80, respectively. For MC FP scores, only the correlation increase from the COMLEX-USA Level 2-CE to Level 3 was statistically significant (for Pearson correlations: z = 2.41, P = .008; for disattenuated correlations: z = 3.16, P < .001). The sensitivity, specificity, and positive and negative predictive values of the COMLEX-USA Level 2-CE with the MC-FP were 0.90, 0.39, 0.96, and 0.19, respectively. CONCLUSIONS: Evidence was found that the COMLEX-USA can assist family medicine residency program directors in predicting later resident performance on the ABFM's ITE and MC-FP, which is becoming increasingly important as graduate medical education accreditation moves toward a single aligned model. PMID- 27254015 TI - Priority Areas and Potential Solutions for Successful Integration and Sustainment of Health Systems Science in Undergraduate Medical Education. AB - Educators, policy makers, and health systems leaders are calling for significant reform of undergraduate medical education (UME) and graduate medical education (GME) programs to meet the evolving needs of the health care system. Nationally, several schools have initiated innovative curricula in both classroom and workplace learning experiences to promote education in health systems science (HSS), which includes topics such as value-based care, health system improvement, and population and public health. However, the successful implementation of HSS curricula across schools is challenged by issues of curriculum design, assessment, culture, and accreditation, among others. In this report of a working conference using thematic analysis of workshop recommendations and experiences from 11 U.S. medical schools, the authors describe seven priority areas for the successful integration and sustainment of HSS in educational programs, and associated challenges and potential solutions. In 2015, following regular HSS workgroup phone calls and an Accelerating Change in Medical Education consortium wide meeting, the authors identified the priority areas: partner with licensing, certifying, and accrediting bodies; develop comprehensive, standardized, and integrated curricula; develop, standardize, and align assessments; improve the UME to GME transition; enhance teachers' knowledge and skills, and incentives for teachers; demonstrate value added to the health system; and address the hidden curriculum. These priority areas and their potential solutions can be used by individual schools and HSS education collaboratives to further outline and delineate the steps needed to create, deliver, study, and sustain effective HSS curricula with an eye toward integration with the basic and clinical sciences curricula. PMID- 27254016 TI - Public Confidence in the Health Care System 1 Year After the Start of the Ebola Virus Disease Outbreak - Sierra Leone, July 2015. AB - Ensuring confidence in the health care system has been a challenge to Ebola virus disease (Ebola) response and recovery efforts in Sierra Leone (1). A national multistage cluster-sampled household survey to assess knowledge, attitudes, and practices (KAP) related to Sierra Leone's health care system was conducted in July 2015. Among 3,564 respondents, 93% were confident that a health care facility could treat suspected Ebola cases, and approximately 90% had confidence in the health system's ability to provide non-Ebola services, including immunizations, antenatal care, and maternity care. Respondents in districts with ongoing Ebola transmission ("active districts") and respondents with higher educational levels reported more confidence in the health care system than did respondents in nonactive districts and respondents with less education. Active districts were the focus of the Ebola response; these districts implemented intensified social mobilization and communication efforts, and established district response centers, Ebola-specific health care facilities, and ambulances. Greater infrastructure and response capacity might have resulted in higher confidence in the health care system in these areas. Respondents ranked Ebola and malaria as the country's most important health issues. Health system recovery efforts in Sierra Leone can build on existing public confidence in the health system. PMID- 27254017 TI - Use of the Violence Risk Scale-Sexual Offender Version and the Stable 2007 to assess dynamic sexual violence risk in a sample of treated sexual offenders. AB - The present study provides an examination of dynamic sexual violence risk featuring the Stable-2007 (Hanson, Harris, Scott, & Helmus, 2007) and the Violence Risk Scale-Sexual Offender version (VRS-SO; Wong, Olver, Nicholaichuk, & Gordon, 2003) in a Canadian sample of 180 federally incarcerated sexual offenders who attended a high-intensity sexual offender treatment program. Archival pretreatment and posttreatment ratings were completed on the VRS-SO and Stable 2007, and recidivism data were obtained from official criminal records, with the sample being followed up approximately 10 years postrelease. VRS-SO pre- and posttreatment dynamic scores demonstrated significant predictive accuracy for sexual, nonsexual violent, any violent (including sexual), and general recidivism, while Stable-2007 pre- and posttreatment scores were significantly associated with the latter 3 outcomes; these associations were maintained after controlling for the Static-99R (Helmus, Thornton, Hanson, & Babchishin, 2012). Finally, significant pre-post differences, amounting to approximately three quarters of a standard deviation, were found on Stable-2007 and VRS-SO scores. VRS-SO change scores were significantly associated with reductions in nonsexual violent, any violent, and general recidivism (but not sexual recidivism) after controlling for baseline risk or pretreatment score, while Stable-2007 change scores did not significantly predict reductions in any recidivism outcomes. Applications of these tools within the context of dynamic sexual violence risk assessment incorporating the use of change information are discussed. (PsycINFO Database Record PMID- 27254018 TI - Development and validation of a multifactor mindfulness scale in youth: The Comprehensive Inventory of Mindfulness Experiences-Adolescents (CHIME-A). AB - Mindfulness-based interventions show consistent benefits in adults for a range of pathologies, but exploration of these approaches in youth is an emergent field, with limited measures of mindfulness for this population. This study aimed to investigate whether multifactor scales of mindfulness can be used in adolescents. A series of studies are presented assessing the performance of a recently developed adult measure, the Comprehensive Inventory of Mindfulness Experiences (CHIME) in 4 early adolescent samples. Study 1 was an investigation of how well the full adult measure (37 items) was understood by youth (N = 292). Study 2 piloted a revision of items in child friendly language with a small group (N = 48). The refined questionnaire for adolescents (CHIME-A) was then tested in Study 3 in a larger sample (N = 461) and subjected to exploratory factor analysis and a range of external validity measures. Study 4 was a confirmatory factor analysis in a new sample (N = 498) with additional external validity measures. Study 5 tested temporal stability (N = 120). Results supported an 8-factor 25-item measure of mindfulness in adolescents, with excellent model fit indices and sound internal consistency for the 8 subscales. Although the CFA supported an overarching factor, internal reliability of a combined total score was poor. The development of a multifactor measure represents a first step toward testing developmental models of mindfulness in young people. This in turn will aid construction of evidence based interventions that are not simply downward derivations of adult mindfulness programs. (PsycINFO Database Record PMID- 27254019 TI - Basic dimensions defining mania risk: A structural approach. AB - Mania is the core criterion for bipolar disorder, a chronic and severe psychiatric illness centrally associated with positive affective disturbance. Many self-report measures have been created to assess symptoms of, and risk for, mania but there are notable disparities in their length, scope, and content. Thus, the goal of this study was to determine the structure and correlates of a number of widely used "bipolar-relevant" (BR) measures (e.g., Hypomanic Personality Scale, Altman Self-Rating Mania Scale, General Behavior Inventory, Mood Disorder Questionnaire). Data from a community sample (Study 1, N = 329) and a student sample assessed at two time points (Study 2; Ns = 382 and 308, respectively) provided strong evidence that the BR measures were characterized by both (a) a well-defined common dimension when a single factor was extracted, and (b) a clear structure of Emotional Lability and Activated Positive Affect upon extracting two factors. The general factor showed a relatively nonspecific pattern of associations with personality and psychopathology. In contrast, the Emotional Lability factor showed its strongest relations with neuroticism and depressive symptoms, displaying comparatively weaker relations with measures of extraversion and positive emotionality. Conversely, although Activated Positive Affect also associated positively with depressive symptoms and with neuroticism in some instances, its strongest relations were with measures of extraversion and high arousal positive emotionality. These findings suggest that measures defining Emotional Lability seem to assess mood volatility to a greater extent, whereas measures defining the Activated Positive Affect factor capture an intense, high arousal form of positive emotionality. (PsycINFO Database Record PMID- 27254020 TI - Cognitive-Affective Verbal Learning Test: An integrated measure of affective and neutral words. AB - Despite growing affective-memory research, only 2 potential clinical measures have been published, each with limitations. We describe the development and piloting of an integrated memory measure for neutral and affectively valenced words, the Cognitive-Affective Verbal Learning Test (C-AVLT). The C-AVLT and mood self-report measures were administered to 124 healthy university students in Study 1, with readministration to 40 students after 1 week. In Study 2, the C AVLT and other neuropsychological measures of memory and emotion were administered to 61 patients referred for polysomnogram evaluation of obstructive sleep apnea (OSA). Study 1 supported the C-AVLT's internal and test-retest reliabilities, as well as concurrent validity, that is, the affective-bias scores but not performance scores correlated with self-reported mood. In Study 2, convergent, criterion (specifically cross-sectional concurrent validity), and incremental validity were supported with regard to both performance and affective bias scores within the OSA sample. We demonstrated the C-AVLT is a reliable and clinically useful measure of both memory and affective-processing bias in 2 samples. Future clinical and research recommendations for the C-AVLT are discussed, including broadening normative data and criterion validity data in psychiatric and neurological samples. (PsycINFO Database Record PMID- 27254023 TI - Understanding and optimizing the addition of phytohormones in the culture of microalgae for lipid production. AB - Some studies have described the use of phytohormones in microalgal culture for the production of biodiesel or selected fatty acids. However, no study has determined the amount of phytohormones that maximizes lipid yield. We determined the optimal concentration of auxins and gibberellins (which is between 40 and 60 MUM) in two strains (Scenedemus abundans and Chlorella ellipsoidea) suitable for biodiesel production. More than 3-fold increment was reached with S. abundans and near 7-fold increment with C. ellipsoidea. Furthermore, this work suggests that the improved growth of the microalgae in the presence of the phytohormones was due to a reduction in the level of reactive oxygen species (ROS) in the cells. An economic analysis showed that, due to its low cost, auxin offers a positive cost benefit balance and therefore could be used at large scale. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1203-1211, 2016. PMID- 27254021 TI - Endogenous Mouse Dicer Is an Exclusively Cytoplasmic Protein. AB - Dicer is a large multi-domain protein responsible for the ultimate step of microRNA and short-interfering RNA biogenesis. In human and mouse cell lines, Dicer has been shown to be important in the nuclear clearance of dsRNA as well as the establishment of chromatin modifications. Here we set out to unambiguously define the cellular localization of Dicer in mice to understand if this is a conserved feature of mammalian Dicer in vivo. To this end, we utilized an endogenously epitope tagged Dicer knock-in mouse allele. From primary mouse cell lines and adult tissues, we determined with certainty by biochemical fractionation and confocal immunofluorescence microscopy that endogenous Dicer is exclusively cytoplasmic. We ruled out the possibility that a fraction of Dicer shuttles to and from the nucleus as well as that FGF or DNA damage signaling induce Dicer nuclear translocation. We also explored Dicer localization during the dynamic and developmental context of embryogenesis, where Dicer is ubiquitously expressed and strictly cytoplasmic in all three germ layers as well as extraembryonic tissues. Our data exclude a direct role for Dicer in the nuclear RNA processing in the mouse. PMID- 27254022 TI - Changing characteristics of livestock-associated meticillin-resistant Staphylococcus aureus isolated from humans - emergence of a subclade transmitted without livestock exposure, the Netherlands, 2003 to 2014. AB - Since 2007, livestock-associated meticillin-resistant Staphylococcus aureus (LA MRSA) has become the predominant MRSA clade isolated from humans in the Netherlands. To assess possible temporal changes, we molecularly characterised over 9,000 LA-MRSA isolates submitted from 2003 to 2014 to the Dutch MRSA surveillance. After an initial rapid increase with a peak in 2009 (n = 1,368), the total number of submitted LA-MRSA isolates has been slowly decreasing to 968 in 2014 and over 80% of LA-MRSA belonged to one of three predominant MLVA/spa types. Next generation sequencing (n=118) showed that MT569/t034 isolates were genetically more diverse than MT398/t011 and MT572/t108. Concurrent with the decrease in LA-MRSA, fewer people reported having contact with livestock and this was most prominent for people carrying MT569/t034 LA-MRSA. The proportion of LA MRSA isolated from infection-related materials increased from 6% in 2009, to 13% in 2014 and most of these isolates originated from patients older than 50 years of age. Remarkably, 83% of these patients reported not having contact with livestock. The results reveal an ongoing change in the genotypic and epidemiological characteristics of Dutch LA-MRSA isolated from humans with the emergence of a LA-MRSA subclade independent of livestock exposure, suggesting LA MRSA starts to resemble non-LA-MRSA in terms of transmissibility and pathogenicity. PMID- 27254024 TI - Correction: Substituent interference on supramolecular assembly in urea gelators: synthesis, structure prediction and NMR. AB - Correction for 'Substituent interference on supramolecular assembly in urea gelators: synthesis, structure prediction and NMR' by Francesca Piana et al., Soft Matter, 2016, 12, 4034-4043. PMID- 27254025 TI - Corkscrew Seals: Grey Seal (Halichoerus grypus) Infanticide and Cannibalism May Indicate the Cause of Spiral Lacerations in Seals. AB - Large numbers of dead seals with characteristic spiral lesions have been washing ashore around the North Atlantic over the past two decades. Interactions with ship propellers and shark predation have been suggested as the likely causal mechanisms. However, new evidence points towards a more likely candidate: grey seal predation. An adult male grey seal was observed and recorded catching, killing and eating five weaned grey seal pups over a period of one week on the Isle of May, Scotland. A further 9 carcasses found in the same area exhibited similar injuries. Post mortem analysis of lesions indicated the wound characteristics were similar to each other and in 12 of the 14 carcasses analysed, were indistinguishable from carcasses previously attributed to propeller interaction. We therefore propose that most of the seal carcasses displaying spiral lacerations in the UK are caused by grey seal predation. Cases in other locations should be re-evaluated using the scoring system presented here to identify whether grey seal predation is a major cause of mortality in phocid seals. PMID- 27254026 TI - Effects of neoadjuvant chemo or chemoradiotherapy for oesophageal cancer on perioperative haemodynamics: A prospective cohort study within a randomised clinical trial. AB - BACKGROUND: Neoadjuvant chemoradiotherapy might improve oncological outcome compared with chemotherapy after surgery for oesophagus or gastrooesophageal junction cancer. However, radiotherapy may induce cardiovascular side-effects that could increase the risk of perioperative adverse effects and postoperative morbidity. OBJECTIVES: The aim of this study was to compare the perioperative haemodynamics in patients undergoing oesophagectomy following neoadjuvant chemotherapy or chemoradiotherapy for cancer. DESIGN: A prospective single-centre cohort study within a randomised multi-centre trial. SETTING: A Swedish University Hospital from January 2009 to March 2013. PATIENTS: A total of 31 patients (chemotherapy 17, chemoradiotherapy 14) included in a multi-centre trial randomising chemotherapy vs. chemoradiotherapy and operated at Karolinska University Hospital, Huddinge. INTERVENTIONS: Cisplatin and 5-fluorouracil, either with or without concurrent radiotherapy (40 Gy), were given prior to surgery. Cardiac function was assessed with LiDCOplus (LiDCO Ltd, London, United Kingdom), echocardiography, troponin T and N-terminal pro-B-type natriuretic peptide, before, during and after surgery. MAIN OUTCOME MEASURES: The primary outcome was the interaction effect of the neoadjuvant treatment on stroke volume index during the perioperative period. Secondary outcomes were the interaction effects of oxygen delivery index, cardiac index, echocardiography and biochemical markers. RESULTS: The groups were matched regarding comorbidities, but patients in the chemoradiotherapy group were older (66 vs. 60 years P = 0.03). Haemodynamic values changed in a similar way in both groups during the study period. The chemoradiotherapy group had a lower cardiac index before surgery (2.9 vs. 3.4 l min m, P = 0.03). On the third postoperative day, both groups displayed a hyperdynamic state compared with baseline, with no increase in troponin T, and a similar increase in N-terminal pro-B-type natriuretic peptide. CONCLUSION: Neoadjuvant chemoradiotherapy for oesophageal or gastrooesophageal junction cancer seems to induce only a marginal negative effect on cardiac function compared with neoadjuvant chemotherapy. This difference did not remain when patients' haemodynamics were challenged by surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01362127. PMID- 27254027 TI - Reply to: survival after long-term isoflurane sedation in critically ill surgical patients. PMID- 27254028 TI - Immunogenicity and Safety of 13-valent Pneumococcal Conjugate Vaccine Compared With 7-valent Pneumococcal Conjugate Vaccine Among Healthy Infants in China. AB - BACKGROUND: Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) were compared with 7-valent pneumococcal conjugate vaccine (PCV7) in Chinese infants. METHODS: Healthy infants aged 2 months were randomized to a double-blind 3-dose infant series plus 1 toddler dose of PCV7 or PCV13 at 3, 4, 5 and 12 months or open-label PCV13 at 2, 4, 6 and 12 months. Serotype-specific immunoglobulin G (IgG) binding and functionality were measured 1 month after the infant series and after the toddler dose. Local reactions, systemic events and adverse events were assessed postvaccination. RESULTS: For the 7 common serotypes, serotype-specific binding IgGs elicited by PCV13 were noninferior to PCV7 after the 3-dose infant series; functional antibodies were comparable. For the 6 additional serotypes, PCV13 recipients had significantly higher serotype specific IgGs and functional antibodies than PCV7 recipients after the infant series. The toddler dose boosted the immune response. Local reactions and systemic events were mild in severity and similar across groups. No new safety signals were identified. CONCLUSIONS: For the 7 common serotypes, serotype specific binding IgG after 2 different 3-dose regimens of PCV13 were noninferior to PCV7 responses. PCV13 recipients had significantly higher immune responses to the 6 additional serotypes. PCV13 is expected to provide pneumococcal disease protection comparable to PCV7 for the common serotypes and further protection against disease caused by the 6 additional serotypes. Safety of PCV7 and PCV13 was comparable. PMID- 27254029 TI - Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study. AB - BACKGROUND: Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES: To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS: In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephonic interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS: Twenty seven percent of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months [odds ratio (OR) = 1.71, P = 0.01, 95% confidence interval (CI): 1.13-2.61], outdoor temperatures between 5 and 10 degrees C (OR = 2.33, P = 0.001, 95% CI: 1.41-3.86), older siblings (OR = 2.60, P = 0.001, 95% CI: 1.50-4.51) and childcare attendance (OR = 1.53, P = 0.07, 95% CI: 0.96-2.44). Fifty-one percent of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first 3 months of life (OR = 0.34, P = 0.003, 95% CI: 0.17-0.69) and in infants with atopic mothers (OR = 0.44, P = 0.008, 95% CI: 0.24-0.80). Increased tidal volume (OR = 1.67, P = 0.03, 95% CI: 1.04-2.68) and outdoor temperatures between 2 and 5 degrees C (OR = 2.79, P = 0.02, 95% CI: 1.17-6.61) were associated with more symptoms. CONCLUSIONS: RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy or premorbid lung function. PMID- 27254030 TI - A Systematic Review of the Effect of Rotavirus Vaccination on Diarrhea Outcomes Among Children Younger Than 5 Years. AB - BACKGROUND: Rotavirus is the leading cause of vaccine-preventable diarrhea among children under 5 globally. Rotavirus vaccination has been shown to prevent severe rotavirus infections with varying efficacy and effectiveness by region. METHODS: We sought to generate updated region-specific estimates of rotavirus vaccine efficacy and effectiveness. We systematically reviewed published vaccine efficacy and effectiveness studies to assess the region-specific effect of rotavirus vaccination on select diarrheal morbidity and mortality outcomes in children under 5 years of age. We employed meta-analytic methods to generate pooled effect sizes by Millennium Development Goal region. RESULTS: Rotavirus vaccination was both efficacious and effective in preventing rotavirus diarrhea, severe rotavirus diarrhea and rotavirus hospitalizations among children under 5 across all regions represented by the 48 included studies. Efficacy against severe rotavirus diarrhea ranged from 90.6% [95% confidence interval (CI): 82.3-95.0] in the developed region to 88.4% (95% CI: 67.1-95.9) in Eastern/Southeastern Asia, 79.6% (95% CI: 71.3-85.5) in Latin America and the Caribbean, 50.0% (95% CI: 34.4-61.9) in Southern Asia and 46.1% (95% CI: 29.1-59.1) in sub-Saharan Africa. Region specific effectiveness followed a similar pattern. There was also evidence of vaccine efficacy against severe diarrhea and diarrheal hospitalizations. CONCLUSION: Our findings confirm the protective efficacy and effectiveness of rotavirus vaccination against rotavirus diarrheal outcomes among children under 5 globally. PMID- 27254031 TI - Dyslipidemia, Diet and Physical Exercise in Children on Treatment With Antiretroviral Medication in El Salvador: A Cross-sectional Study. AB - BACKGROUND: Dyslipidemias are common in HIV-infected children, especially if treated with protease inhibitors, but there are few data on how to treat dyslipidemias in this population. We estimated the dyslipidemia prevalence and its association with treatment, diet and physical exercise in children on antiretroviral treatment at the El Salvador reference center for pediatric HIV care (CENID). METHODS: Information was gathered regarding socio-demographic characteristics, treatment, diet and physical activity of 173 children aged 5-18 years and receiving antiretroviral therapy. Triglycerides, total cholesterol, low density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), viral load and CD4 T-lymphocytes were measured. Abnormal concentrations were defined as triglycerides >=130 mg/dL in 10- to 18-year olds and >=100 mg/dL in <10-year olds; total cholesterol >=200 mg/dL; LDL-C >=130 mg/dL and HDL-C <=35 mg/dL. We adjusted 4 different multivariate models to assess the independent association of each type of dyslipidemia with protease inhibitors, diet and physical exercise. RESULTS: Of the 173 children, 83 (48%) had hypertriglyceridemia and 25 (14.5%) hypercholesterolemia. High LDL-C concentrations were observed in 17 children (9.8%) and low HDL-C in 38 (22%). Treatment with protease inhibitors was significantly associated with hypertriglyceridemia [prevalence ratio (PR) 2.8; 95% confidence interval (CI): 2.0-3.8] and hypercholesterolemia (PR 9.0; 95% CI: 3.6-22.2). Higher adherence to a "high fat/sugar diet" was associated with hypercholesterolemia (PR 1.6; 95% CI: 1.1-2.3) and high LDL-C (PR 1.7; 95% CI: 1.0-2.9). Compared with those exercising <3 times/week, children exercising >=7 times were less likely to have low HDL-C (PR = 0.4; 95% CI: 0.2-0.7). CONCLUSIONS: These results suggest that a healthy diet and exercise habits can contribute to controlling some aspects of the lipid profile in this population. PMID- 27254032 TI - Living Conditions as a Driving Factor in Persistent Methicillin-resistant Staphylococcus aureus Colonization Among HIV-infected Youth. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization has been linked to HIV-related sexual and social behaviors. MRSA risk factors may be different for HIV-infected children, adolescents and young adults. We investigated the association of MRSA colonization, persistent colonization and genotypes with potential risk factors among HIV-infected youth. METHODS: For this case-control study, patients 24 years of age or younger attending 2 HIV reference centers were recruited from February to August 2012 and followed for 1 year. Nasal swabs were collected at enrollment and every 3 months. MRSA clones were characterized by staphylococcal chromosomal cassette mec typing, spa typing and multilocus sequence typing. We compared MRSA colonization and persistent colonization with patient demographic and clinical characteristics. RESULTS: Among 117 participants, MRSA colonization frequency (calculated for each collection based on the number of positive cultures per patient) was 12.8% at the first collection. The average MRSA colonization frequency was 10.4%. Our results showed 11.1% were persistent carriers (subjects with more than 1 positive culture in at least 3). Crowding was the only factor associated with MRSA colonization (P = 0.018). Persistent carriers had significantly higher (4.2 times) odds of living in a crowded household (95% confidence interval-1.1-16.2). We observed high genetic diversity among MRSA isolates, with t002/ST5 and t318/ST30 being the most frequent. CONCLUSIONS: MRSA colonization among HIV-infected youth is more closely related to living in a low-income or slum community than to HIV-related clinical factors. High genetic MRSA isolate diversity in our population suggests frequent transmission. PMID- 27254033 TI - Rotavirus Serum IgA Immune Response in Children Receiving Rotarix Coadministered With bOPV or IPV. AB - BACKGROUND: Vaccine schedules including bivalent oral and inactivated poliovirus vaccines will replace trivalent oral poliovirus vaccines in 2016. METHODS: We evaluated rotavirus immunoglobulin A seroresponses when the second dose of Rotarix at 16 weeks was given concomitantly with inactivated or bivalent oral poliovirus vaccines. RESULTS: Rotavirus immunoglobulin A seroresponse rate at week 28 was 15% lower in recipients of bivalent oral poliovirus vaccines compared with inactivated poliovirus vaccines. CONCLUSION: Bivalent oral poliovirus vaccine decreases rotavirus IgA seroresponse rates when coadministered at 16 weeks of age. PMID- 27254034 TI - Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril) When Administered Concomitantly With a Tetravalent Dengue Vaccine Candidate in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru: A Randomized Trial. AB - BACKGROUND: Dengue and yellow fever (YF) viruses are closely related members of the Flaviviridae family. Given the inherent similarities between the YF vaccine and dengue vaccine (CYD-TDV) candidate, it is possible that the latter could interfere with the response to the licensed YF vaccine when coadministered. METHODS: In this randomized, observer-blind, controlled, phase III trial, conducted in Colombia and Peru, 787 toddlers were administered YF vaccine concomitantly with CYD-TDV (group 1) or placebo (group 2), followed by CYD-TDV after 6 and 12 months. YF and dengue neutralizing antibody titers were determined using a 50% plaque reduction neutralization test. Noninferiority was demonstrated if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates [(YF + CYD-TDV) - YF alone] was greater than -10%. The safety of both vaccines was also assessed. RESULTS: Concomitant administration of YF with either CYD-TDV or placebo yielded YF seroconversion rates of 100.0% and 99.7%, respectively. The difference in YF seroconversion rates between the 2 groups was 0.33% (95% confidence interval:0.98; 1.87), demonstrating that the immune response against YF administered concomitantly with CYD-TDV was noninferior to YF administered with placebo. After 2 injections of CYD-TDV, the percentage of participants with dengue titres >=10 (1/dil) for the 4 dengue serotypes were 91.2%-100% for group 1 and 97.2%-100% in group 2. There were no safety concerns during the study period. CONCLUSIONS: Concomitant administration of YF vaccine with CYD-TDV has no relevant impact on the immunogenicity or safety profile of the YF vaccine. PMID- 27254035 TI - Nonactivated Protein C in the Treatment of Neonatal Sepsis: A Retrospective Analysis of Outcome. AB - BACKGROUND: Previously, we found that plasma protein C (PC) activity <=10% significantly increased the probability of the occurrence of death during neonatal sepsis. Accordingly, if the activity of plasma PC declined during the course of sepsis to <=10%, we administered a nonactivated PC zymogen to increase a PC activity. The aim of that retrospective analysis was to explore treatment effects of PC zymogen supplementation in septic infants, with plasma PC activity <=10%. METHODS: A database was used to locate 85 newborns treated with PC from among 458 analyzed infants with confirmed sepsis. RESULTS: The median birth weight and gestational age of treated infants were, respectively, 1010.0 g and 29 weeks. In 47 infants, early-onset sepsis developed, whereas in 38 neonates, late onset sepsis was recognized. PC was given as a single dose of 200 IU/kg. Among 458 septic patients, death occurred in 19 newborns (4.2%), exclusively in infants with plasma PC activity <=10%. In 15 infants, death occurred in the course of early-onset sepsis and 4 newborns died of late-onset sepsis (early-onset sepsis vs. late-onset sepsis; P = 0.036; chi with the Yates correction). CONCLUSIONS: An increased risk of death in septic neonates with plasma PC activity <=10% suggests the necessity for its evaluation and possibility of supplementation of PC zymogen. PMID- 27254036 TI - Handshake Stewardship: A Highly Effective Rounding-based Antimicrobial Optimization Service. AB - BACKGROUND: Implementation of an antimicrobial stewardship program is recommended as one solution to combat increasing antimicrobial resistance. Most antimicrobial stewardship programs use preauthorization or restrictive strategies recommended in national guidelines. We describe a unique, rounding-based strategy, handshake stewardship. Handshake stewardship is distinguished by: (1) lack of restriction and preauthorization, (2) review of all prescribed antimicrobials and (3) a rounding-based, in-person approach to feedback by a pharmacist-physician team. METHODS: We retrospectively measured antimicrobial use hospital-wide and by unit during preimplementation, planning, and postimplementation phases of the handshake stewardship approach to determine the efficacy of this strategy in decreasing use in a freestanding children's hospital. All antimicrobials prescribed on the inpatient services between October 2010 and September 2014 were included in the review. Monthly antimicrobial use (hospital-wide and by unit) was measured in days of therapy per 1000 patient days (DOT/1000 PD). RESULTS: Overall antimicrobial use decreased by 10.9% during the 4 years of the analysis (942 to 839 DOT/1000 PD, P < 0.01), with an impact of 10.3% on antibacterials (750 to 673 DOT/1000 PD, P < 0.01). Vancomycin use decreased by 25.7% (105 to 78 DOT/1000 PD, P < 0.01). Meropenem use decreased by 22.2% (45 to 35 DOT/1000 PD, P = 0.04) without a compensatory increase of other antipseudomonal agents. Decreased usage was observed both hospital-wide and on individual units for most agents. CONCLUSIONS: The handshake stewardship approach is an effective strategy for an antimicrobial stewardship program, as demonstrated by the widespread and significant decrease in antimicrobial use after implementation. PMID- 27254037 TI - Safety and Immunogenicity of M-M-RII (Combination Measles-Mumps-Rubella Vaccine) in Clinical Trials of Healthy Children Conducted Between 1988 and 2009. AB - BACKGROUND: M-M-RII, a combination measles, mumps and rubella vaccine, was licensed in the United States in 1978 based on data from several clinical trials that demonstrated that the safety and immunogenicity of the vaccine were comparable to the component monovalent vaccines and to the previous trivalent combination vaccine. METHODS: Safety and immunogenicity data from 23 postlicensure clinical trials conducted with M-M-RII between 1988 and 2009 were summarized. A total of 12,901 children who received only a first dose, 920 children who received a first and second dose and 400 children who received only a second dose were evaluated. RESULTS: The vaccine was generally well tolerated among children who received a first and/or second dose of M-M-RII. During the 28 42-day follow-up after dose 1 and dose 2, the median rate of temperatures >=102 degrees F (oral equivalent) was 24.8% and 13.0% and the median rate of measles/rubella-like rash was 3.2% and 0.5%, respectively. The median rate of injection-site reactions during the first 5 days postdose 1 and postdose 2 was 17.3% and 42.7%, respectively. The seroconversion rates (enzyme-linked immunosorbent assay) after dose 1 were remarkably consistent from study to study between 1988 and 2009 (92.8%-100% for measles, 97.7%-100% for mumps and 92.8% 100% for rubella). A trend test showed that there was no change in the immunogenicity of the vaccine over the 21-year period. CONCLUSIONS: The results of this analysis demonstrate that M-M-RII is well tolerated and immunogenic. The vaccine performed consistently over 21 years of evaluation in clinical trials. PMID- 27254038 TI - Use of Ceftolozane/Tazobactam in the Treatment of Multidrug-resistant Pseudomonas aeruginosa Bloodstream Infection in a Pediatric Leukemia Patient. AB - Multidrug-resistant Pseudomonas aeruginosa is of increasing concern in pediatric patients. Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant Pseudomonas; however, no data exist on its use in children. This report summarizes the treatment of a multidrug-resistant P. aeruginosa bloodstream infection in a pediatric leukemia patient with ceftolozane/tazobactam and provides the first description of its pharmacokinetics in pediatrics. PMID- 27254039 TI - Subdural Empyema Caused by Neisseria meningitidis: A Case Report and Review of the Literature. AB - Subdural empyema complicating meningococcal meningitis is rare. We describe a case and 14 previously reported cases; all had persistent fever and 12 had seizures. Initial cerebrospinal fluid showed raised protein with low glucose values. Neuroimaging confirmed the diagnosis in all cases where undertaken. Ten children had neurosurgical intervention. Clinical outcome was available in 14 cases; a full recovery was reported in 10 and 1 child died. PMID- 27254041 TI - Pediatricians as Adolescent Ambassadors. PMID- 27254040 TI - Association between Exposure to Smartphones and Ocular Health in Adolescents. AB - PURPOSE: Smartphone use has dramatically increased in recent years. Smartphones may have adverse health effects, particularly on the eyes, because users stare at the screen for a much longer time than they do with ordinary mobile phones. The objective of this study was to elucidate the relationship between smartphone use and ocular symptoms among adolescents. METHODS: Information on smartphone use and ocular symptoms (blurring, redness, visual disturbance, secretion, inflammation, lacrimation and dryness) related to eye fatigue and strain from 715 adolescent subjects from three cities in Korea was obtained using a structured questionnaire. Ocular health was scored using number of ocular symptoms. Odds ratios (ORs), 95% confidence intervals (95% CIs) and p-values for ocular symptoms were calculated with binomial and multinomial logistic regression models. RESULTS: Higher prevalence rates for ocular symptoms were observed in groups with greater exposure to smartphones (p < 0.05). Longer daily smartphone use was associated with a higher likelihood of having multiple ocular symptoms (5-7 symptoms out of 7 symptoms; p = 0.005). Excessive/intermittent use (>2 hours daily and <=2 hours continuously) and excessive/persistent use (>2 hours daily and >2 hours continuously) compared to shorter use (<2 hours daily) were associated with multiple ocular symptoms (OR 2.18, 95% CI 1.09-4.39; OR 2.26, 95% CI 1.11-4.57, respectively). A higher lifetime exposure to smartphones was associated with a higher likelihood of having multiple ocular symptoms (OR 3.05, 95% CI 1.51-6.19; p = 0.001). CONCLUSION: Increasing exposure to smartphones can have a negative impact on ocular health in adolescents. PMID- 27254042 TI - Onset of Puberty in Relation to Obesity. PMID- 27254043 TI - Phenobarbital for Neonatal Seizures: A Time for Perusal. PMID- 27254044 TI - Age of Onset of Puberty in Apparently Healthy School Girls from Northern India. AB - OBJECTIVE: To determine the age of pubertal onset and menarche in school-going girls, and to assess the impact of obesity on pubertal timing. DESIGN: Cross sectional. SETTING: Seven schools across Delhi, India. PARTICIPANTS: 2010 school girls, aged 6-17 years. METHODS: Anthropometric measurement and pubertal staging was performed for all subjects. Menarche was recorded by status quo method. Body mass index was used to define overweight/obesity. Serum gonadotropins and serum estradiol were measured in every sixth participant. MAIN OUTCOME MEASURES: Age at thelarche and menarche analyzed for entire cohort and stratified based on body mass index. RESULTS: Median (95% CI) ages of thelarche, pubarche and menarche were 10.8 (10.7-10.9) y, 11.0. y (10.8-11.2) y and 12.4 y (12.2-12.5) y. Overweight/obese girls showed six months earlier onset of thelarche and menarche than those with normal BMI (P<0.05). Serum gonadotropins did not vary significantly in overweight/obese subjects. CONCLUSION: The study provides the normative data for pubertal growth in Indian girls. Pubertal onset occurs earlier in overweight and obese girls. PMID- 27254045 TI - Serum Phenobarbitone Levels in Term and Near Term Neonates with Seizures. AB - OBJECTIVE: To evaluate serum phenobarbitone levels in neonates with seizures and to evaluate the effect of repeated loading dose on serum phenobarbitone levels. METHODS: In this prospective observational study conducted in a tertiary care centre of Northern India during 2011- 2012, 99 neonates admitted with seizureswere included.Serum phenobarbitone levels in neonates with seizures at 20 minutes and 12 hours after the first loading dose of phenobarbitone were measured. RESULTS: Serum phenobarbitone levels [mean (SD)] at 20 min and 12 hours was 27.3 (28.4) ug/mL and 23 (19.1) ug/mL, respectively (P=0.07). The mean serum phenobarbitone levels 12 hours after the loading dose, and proportion of neonates with toxic levels increased with each loading dose of intravenous phenobarbitone. CONCLUSION: Monitoring of serum level of phonobarbitone may not be essential because seizure control in neonates appears to be independent of whether serum level is subtherapeutic, therapeutic or toxic range. PMID- 27254046 TI - Neurodevelopmental Outcome of Extremely Low Birth Weight Children at Corrected Age of Two Years. AB - OBJECTIVE: To assess the neurodevelopmental, cognitive and behavioral function of extremely low birth weight babies (ELBW) till corrected age of two years. METHODS: 79 ELBW babies were enrolled and followed at 1 year (n=50), 18 months (n=47) and 2 years (n=36). Adverse composite outcome was defined as death or moderate-to-severe neurodevelopmental impairment (defined as either cerebral palsy or DQ score <70 or deafness or blindness). RESULTS: At 1 year, 24% were neurologically abnormal. At 18 months, average score (>85) was seen in 25 (54%) children in motor and 8 (17%) in mental development. Abnormal behavioral score (?12) was seen in 89% children. Adverse composite outcome was present in 28 (35.4%) babies. CONCLUSIONS: ELBW neonates are at a high risk of neurodevelopmental and behavioral impairment. PMID- 27254047 TI - Lactose and Fructose Intolerance in Turkish Children with Chronic Abdominal Pain. AB - OBJECTIVE: To investigate the prevalence of lactose and fructose intolerance in children with chronic abdominal pain. METHODS: Hydrogen breath tests were done to detect lactose and fructose malabsorption in 86 children with chronic abdominal pain (44 irritable bowel syndrome, 24 functional abdominal pain and 17 functional abdominal pain syndrome as per Rome III criteria) presenting to a Pediatric Gastroentreology department. RESULTS: 14 (16.3%) of patients were diagnosed with lactose intolerance and 11 (12.8%) with fructose intolerance. CONCLUSION: Lactose and fructose intolerance in children can lead to chronic abdominal pain and symptoms improve with dietary modifications. PMID- 27254048 TI - Outbreaks of Hypoglycemic Encephalopathy in Muzaffarpur, India: Are These Caused by Toxins in Litchi Fruit?: The Point. PMID- 27254049 TI - Outbreaks of Hypoglycemic Encephalopathy in Muzaffarpur, India: Are These Caused by Toxins in Litchi Fruit?: The Counterpoint. PMID- 27254050 TI - Updated Neonatal Resuscitation Guidelines 2015 Major Changes. PMID- 27254051 TI - Writing the Results. PMID- 27254052 TI - Tubercular Meningitis, A Tale of 50 Years. PMID- 27254053 TI - Systematic Review of Effectiveness of Varicella Vaccines: A Critical Appraisal: Evidence based Medicine Viewpoint. PMID- 27254054 TI - Systematic Review of Effectiveness of Varicella Vaccines: A Critical Appraisal: Immunization Experts Viewpoint. PMID- 27254055 TI - Intracranial Hemorrhage Following Intrathecal Methotrexate Therapy for Acute Lymphoblastic Leukaemia. AB - BACKGROUND: Acute toxic leukoencephalopathy following intrathecal methotrexate administration is well documented but intracranial haemorrhage is extremely rare. CASE CHARACTERISTICS: A 2-year-6 months old girl with acute lymphoblastic leukemia developed sudden onset neurological deterioration following intrathecal methotrexate. OBSERVATIONS: Computed tomography scan of brain demonstrated intraventricular and subarachnoid hemorrhage. OUTCOME: Child improved gradually on conservative management. Follow-up neuroimaging showed resolution of hemorrhage. MESSAGE: Intracranial haemorrhage is a rare but serious complication of intrathecal methotrexate. PMID- 27254056 TI - Infantile Bullous Pemphigoid Following Vaccination. AB - BACKGROUND: Post-vaccination infantile bullous pemphigod is a rare presentation. CASE CHARACTERISTICS: A 2-month-old girl presented with widespread bullae, erosions, necrotic and targetoid lesions over body and mucosae after vaccination. Histology and direct immunofluorescence (DIF) were consistent with bullous pemphigoid. INTERVENTION: Clinical remission with oral steroids and no recurrence with subsequent vaccination. MESSAGE: Continuation of vaccination may not be contraindicated in infants where bullous pemphigoid onset occurs after vaccination. PMID- 27254057 TI - Delayed Diagnosis of Dopa responsive Dystonia in Two Siblings. AB - BACKGROUND: Dopa responsive dystonia is characterized by progressive disabling dystonia, diurnal variation and a dramatic response to Levodopa. CASE CHARACTERISTICS: Two siblings presented with regression of motor milestones and hypertonia in lower limbs. History of diurnal variation was present in elder sibling. OUTCOME: Both responded dramatically to Levodopa. The genomic DNA analysis of elder sibling revealed a novel mutation. MESSAGE: A trial of Levodopa should be considered in a child with motor regression with diurnal variation, in the presence of extrapyramidal features. PMID- 27254058 TI - The Crying Child. PMID- 27254059 TI - Psychosocial Care and its Association with Severe Acute Malnutrition. AB - This cross-sectional study compared 120 children having severe acute malnutrition with 120 healthy children for exposure to 40 behaviors, by measuring psychosocial care based on Home Observation for Measurement of the Environment (HOME) inventory. The mean (SD) psychosocial care score of cases and controls significantly differed [18.2 (2.2) vs 23.5 (2.1); P<0.001]. A score of less than 14 was significantly associated with severe acute malnutrition (OR 23.2; 95% CI 8.2, 50). PMID- 27254060 TI - Oxygen Saturation Index, A Noninvasive Tool for Monitoring Hypoxemic Respiratory Failure in Newborns. PMID- 27254061 TI - Association of Dietary Calcium Intake and Body Fat with Hypertension in Indian Adolescents. AB - To explore association of dietary calcium intake and body composition with blood pressure, 417 apparently healthy adolescents (218 boys) were studied for anthropometry, blood pressure, body composition and nutrient intakes using standard protocols. Blood pressure correlated negatively with dietary calcium (r= -0.120, P<0.01) and positively with body fat (r=0.56,P<0.001). Low dietary calcium intakes and high adiposity may increase risk of hypertension in Indian adolescents. PMID- 27254062 TI - High Mobility Group Box 1 in Preterm Infants with Intraventricular Hemorrhage. AB - We studied the level of high mobility group box 1(HMGB1) in preterm infants with intraventricular hemorrhage (IVH). Using enzyme-linked immunosorbent assay (ELISA), the concentration of HMGB1 in cord blood obtained from 41 infants with IVH and 67 infants without IVH were measured. The cord blood concentration of HMGB1 in infants with IVH were significantly higher than those without IVH (P=0.041). Increased levels of HMGB1 might be associated with IVH in preterm infants. PMID- 27254063 TI - Training Pediatric Emergency Medicine Specialists in India. PMID- 27254064 TI - Training Pediatric Emergency Medicine Specialists in India: Authors Reply. PMID- 27254065 TI - Kawasaki Disease in Jammu and Kashmir. PMID- 27254066 TI - Deep Vein Thrombosis Secondary to Early Onset Sepsis in a Neonate. PMID- 27254067 TI - Filtered Sunlight for Treatment of Neonatal Hyperbilirubinemia, A Rejoinder. PMID- 27254068 TI - Filtered Sunlight for Treatment of Neonatal Hyperbilirubinemia: A Rejoinder,Authors Reply. PMID- 27254069 TI - Is Newborn Hearing Screening Worthwhile in India? PMID- 27254070 TI - Is Newborn Hearing Screening Worthwhile in India?: Authors Reply. PMID- 27254071 TI - Year of Mnemonics and Acronyms. PMID- 27254072 TI - Publication: Predatory Journals and Beall. PMID- 27254073 TI - "Chaplains for Wellbeing" in Primary Care: A Qualitative Investigation of Their Perceived Impact for Patients' Health and Wellbeing. AB - Although Health Chaplaincy services are well-established in hospitals in the United Kingdom and across the world, Primary Care Chaplaincy is still in its infancy and much less extensively developed. This study explored the impact the introduction of a Primary Care "Chaplains for Wellbeing" service had upon patients' experience and perceived health and well-being. Sixteen patients participated in one-one interviews. Transcripts were analyzed using interpretative phenomenological analysis (IPA). Patients reported circumstances that had eroded perceived self-efficacy, self-identity, and security manifesting as existential displacement; summarized under the superordinate theme of "loss." "Loss" originated from a number of sources and was expressed as the loss of hope, self-confidence, self-efficacy, and sense of purpose and meaning. Chaplains used a wide range of strategies enabling patients to rebuild self-confidence and self esteem. Person-centered, dignified, and responsive care offered in a supportive environment enabled patients to adapt and cope with existential displacement. PMID- 27254074 TI - Erratum: (61)Ni synchrotron radiation-based Mossbauer spectroscopy of nickel based nanoparticles with hexagonal structure. PMID- 27254075 TI - Rapid remission of symptomatic brain metastases in melanoma by programmed-death receptor-1 inhibition. AB - Although ~40% of patients with metastatic melanoma develop brain metastases, the presence of brain metastases often precludes enrolment in clinical trials for advanced melanoma. However, the development of symptomatic brain metastases markedly increases mortality. The antiprogrammed-death-receptor-1 antibody pembrolizumab achieves extracranial metastases disease response rates of up to 50%. Here, we report the rapid and sustained response of symptomatic multifocal brain metastases in a melanoma ipilimumab-pretreated patient under pembrolizumab, combined with high-dose dexamethasone therapy during the induction phase of therapy. Complete remission has been maintained for over 1 year of follow-up and has correlated with the response rate observed in the extracranial metastases. Radiological disease response was identified during the first follow-up visit in the absence of adjuvant radiotherapy. This report highlights the need for further clinical studies to specifically address the therapeutic potential of antiprogrammed-death-receptor-1 monotherapy in the management of untreated brain metastases in melanoma. PMID- 27254076 TI - Factors Influencing the Placebo Effect in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: An Analysis of Two Randomized Clinical Trials. AB - OBJECTIVE: To explore factors related to the placebo effect in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). METHODS: This was a retrospective cohort study of patients with POAG and patients with OH who were treated with placebo. The patients' data were extracted from two randomized, double-masked, parallel, multicenter clinical trials (trial 1 and trial 2) in Japan. We explored the baseline factors that were associated with the intraocular pressure (IOP)-lowering effect of placebo ophthalmic solution after 4 weeks of instillation treatment at two time points by using multivariable models. The time points were Hour 0 (between 08:30 and 10:30 before instillation) and Hour 2 (within 1.5 to 2.5 h after instillation and by 12:30) at the baseline date and after 4 weeks. The changes in IOP from baseline to 4 weeks at the two time points were evaluated for the IOP-lowering effect induced by placebo instillation. RESULTS: Of the 330 patients included in the two trials, 89 patients were eligible for the analysis. The results of the multivariable analysis for Hour 0 indicated a high IOP at the baseline date (coefficient: 0.24, 95% confidence interval (CI): 0.02 to 0.46, P = 0.03), and the magnitude of the IOP fluctuation at the baseline date (coefficient: 0.57, 95% CI: 0.24 to 0.90, P = 0.001) was associated with the IOP-lowering effect after 4 weeks. With respect to Hour 2, the trial type was associated with the IOP-lowering effect (coefficient: -1.15, 95% CI: -2.14 to -0.16, P = 0.02). CONCLUSIONS: A large fluctuation in IOP during the day is associated with the IOP-lowering effect induced by placebo in patients with POAG or OH. This finding would be helpful to researchers when designing studies related to glaucoma in the early stages of clinical development of drugs. PMID- 27254077 TI - P2X6 Knockout Mice Exhibit Normal Electrolyte Homeostasis. AB - ATP-mediated signaling is an important regulator of electrolyte transport in the kidney. The purinergic cation channel P2X6 has been previously localized to the distal convoluted tubule (DCT), a nephron segment important for Mg2+ and Na+ reabsorption, but its role in ion transport remains unknown. In this study, P2x6 knockout (P2x6-/-) mice were generated to investigate the role of P2X6 in renal electrolyte transport. The P2x6-/- animals displayed a normal phenotype and did not differ physiologically from wild type mice. Differences in serum concentration and 24-hrs urine excretion of Na+, K+, Mg2+ and Ca2+ were not detected between P2x6+/+, P2x6+/- and P2x6-/- mice. Quantitative PCR was applied to examine potential compensatory changes in renal expression levels of other P2x subunits and electrolyte transporters, including P2x1-5, P2x7, Trpm6, Ncc, Egf, Cldn16, Scnn1, Slc12a3, Slc41a1, Slc41a3, Cnnm2, Kcnj10 and Fxyd2. Additionally, protein levels of P2X2 and P2X4 were assessed in P2x6+/+ and P2x6-/- mouse kidneys. However, significant changes in expression were not detected. Furthermore, no compensatory changes in gene expression could be demonstrated in heart material isolated from P2x6-/- mice. Except for a significant (P<0.05) upregulation of P2x2 in the heart of P2x6-/- mice compared to the P2x6+/+ mice. Thus, our data suggests that purinergic signaling via P2X6 is not significantly involved in the regulation of renal electrolyte handling under normal physiological conditions. PMID- 27254078 TI - Can Visual Illusions Be Used to Facilitate Sport Skill Learning? AB - Recently it has been reported that practicing putting with visual illusions that make the hole appear larger than it actually is leads to longer-lasting performance improvements. Interestingly, from a motor control and learning perspective, it may be possible to actually predict the opposite to occur, as facing a smaller appearing target should enforce performers to be more precise. To test this idea the authors invited participants to practice an aiming task (i.e., a marble-shooting task) with either a visual illusion that made the target appear larger or a visual illusion that made the target appear smaller. They applied a pre-post test design, included a control group training without any illusory effects and increased the amount of practice to 450 trials. In contrast to earlier reports, the results revealed that the group that trained with the visual illusion that made the target look smaller improved performance from pre- to posttest, whereas the group practicing with visual illusions that made the target appear larger did not show any improvements. Notably, also the control group improved from pre- to posttest. The authors conclude that more research is needed to improve our understanding of whether and how visual illusions may be useful training tools for sport skill learning. PMID- 27254079 TI - Observation of Charge Generation and Transfer during CVD Growth of Carbon Nanotubes. AB - Carbon nanotube (CNT) is believed to be the most promising material for next generation IC industries with the prerequisite of chirality specific growth. For various approaches to controlling the chiral indices of CNTs, the key is to deepen the understanding of the catalytic growth mechanism in chemical vapor deposition (CVD). Here we show our discovery that the as-grown CNTs are all negatively charged after Fe-catalyzed CVD process. The extra electrons come from the charge generation and transfer during the growth of CNTs, which indicates that an electrochemical process happens in the surface reaction step. We then designed an in situ measurement equipment, verifying that the CVD growth of CNTs can be regarded as a primary battery system. Furthermore, we found that the variation of the Fermi level in Fe catalysts have a significant impact on the chirality of CNTs when different external electric fields are applied. These findings not only provide a new perspective on the growth of CNTs but also open up new possibilities for controlling the growth of CNTs by electrochemical methods. PMID- 27254080 TI - Highly Ordered Graphene Oxide and Reduced Graphene Oxide Based Polymer Nanocomposites: Promise and Limits for Dynamic Impacts Demonstrated in Model Organic Coatings. AB - Graphene oxide (GO) dispersed in water has been combined with a mixture of aqueous polymer dispersions and melamine formaldehyde resin (MF). Stable low viscous fluids with no obvious signs of mesoscale ordering at 0.3 wt % yield transparent films with GO loadings up to one weight percent in the form of homogeneously aligned double strands, each comprising few individual layers of the carbon allotrope. While baking of the films at 160 degrees C results in minor thermal reduction of GO, in situ reduction with excess hydroxylamine (HA) in the presence of the polymer colloids yields stable dispersions in which amphiphilic graphene like flakes temporarily encapsulate gaseous reaction products. Depending on the parameters in the time-temperature domain, the hollow spheres may be transferred into solid material or disassemble during film formation, the latter case providing black, smooth, and transparent films with up to eight magnitudes increased electrical conductivity and an oxygen permeability 30-fold higher compared to the neat polymer matrix. In contrast, GO reduces oxygen permeability by that factor, while water permeability stays unchanged. Thermo-mechanical measurements reveal matrix stiffening by the platelets as well as by HA, the latter via modifying the MF reactivity. Excellent stone chip resistance and ballistic impact tests demonstrate efficient energy dissipation and crack deflection provided by the laminate like morphology of GO based composite. On the contrary, the same material only provides moderate substrate protection in rain erosion tests. PMID- 27254081 TI - Fn14: a new player in cancer-induced cachexia. AB - PURPOSE OF REVIEW: Although cancer cachexia is a very significant condition that is present in up to 80% of cancer cases, the cause of the condition has remained a puzzle. Cancer cachexia is a condition which is mainly characterised by muscle wasting, mobilization of fat reserves, and overall metabolic disturbance. This review aims to highlight some of the recent findings in cancer cachexia research. RECENT RESEARCH: It has been recently demonstrated that the expression of a single receptor, fibroblast growth factor-inducible 14, on a tumour can initiate cachexia and that this can be completely ablated by treatment with an antibody against this receptor. Also recently described was the role of parathyroid hormone receptor-binding proteins in causing cachexia through a mechanism where white adipose tissue is replaced with brown adipose tissue. In parallel, work done in drosophila suggests that the impaired insulin signalling is a direct cause of cancer cachexia through the release of an insulin growth factor binding protein that inhibits insulin and insulin-like growth factor 1 signalling. SUMMARY: Successful therapies are urgently needed to combat cancer cachexia in the clinic. Recent research is making progress toward discovering the underlying molecular causes of the condition, which could lead to new therapeutic approaches and in the future contribute to more positive clinical outcomes for cancer sufferers. PMID- 27254083 TI - Rejection sensitivity and depressive symptoms: Longitudinal actor-partner effects in adolescent romantic relationships. AB - The present study utilizes the actor-partner interdependence model to examine the longitudinal relationship between rejection sensitivity and one's own and one's partner's depressive symptoms. The sample included adolescent romantic couples from the U.S. (N = 198 adolescents; 50% girls; 90.2% Caucasian) whose rejection sensitivity at Time 1 and depressive symptoms approximately one year later (Time 2) were assessed. Additionally, aggressive behaviors and maintenance behaviors that commonly associated with rejection sensitivity (e.g., self-silencing) are explored as mediators. Results indicate that boyfriends' rejection sensitivity at Time 1 predicted girlfriends' depressive symptoms at Time 2. Additionally, girls' rejection sensitivity predicted their own and their boyfriends' self-silencing. Developmental and clinical implications are discussed. PMID- 27254084 TI - Markers of cerebral small vessel disease and severity of depression in the general population. AB - The vascular depression hypothesis postulates that cerebral small vessel disease can cause or exacerbate depression in elderly persons. Numerous studies explored the association of imaging markers of cerebral small vessel disease including white matter lesions (WMLs) and lacunar infarcts with depressive symptoms or disorders. However, cerebral microbleeds have not been tested in depression. In the current study, we aimed to explore the association of WMLs, lacunar infarcts and cerebral microbleeds with depression continuum in a large population-based sample, the Rotterdam Study. Study population consisted of 3799 participants (aged 45 or over) free of dementia. WML volumes, lacunar infarcts and cerebral microbleeds were measured with brain magnetic resonance imaging. Depressive symptoms, depressive disorders and co-morbid anxiety disorders were assessed with validated questionnaires and clinical interview. WML volumes and lacunar infarcts were associated with depressive symptoms and disorders. Cerebral microbleeds, especially in deep or infratentorial brain regions, were related to depressive disorders only. Our results indicate that WMLs and lacunar infarcts might be non specific vascular lesions seen in depressive symptoms and disorders. Association of cerebral microbleeds with more severe forms of depression may indicate impaired brain iron homeostasis or minor episodes of cerebrovascular extraversion, which may play a role in depression etiology. PMID- 27254085 TI - The effects of white matter disease on the accuracy of automated segmentation. AB - Automated segmentation of the brain is challenging in the presence of brain pathologies such as white matter hyperintensities (WMH). A late-life depression population was used to demonstrate the effect of WMH on brain segmentation and normalization. We used an automated algorithm to detect WMH, and either filled them with normal-appearing white-matter (NAWM) intensities or performed a multi spectral segmentation, and finally compared the standard approach to the WMH filling or multi-spectral segmentation approach using intra-class correlation coefficients (ICC). The presence of WMH affected segmentations for both approaches suggesting that studies investigating structural differences in populations with high WMH should account for WMH. We also investigated how functional data contrasts are affected using normalization between the standard compared to fill and multi-spectral approach. We found that the functional data was not affected. While replication with a larger sample is needed, this study shows that WMH can significantly affect the results of segmentation and these areas are not limited to those affected by WMH. It is clear that to study gray matter differences that some correction should be made to account for WMH. Future studies should investigate which methods for accounting for WMH are most effective. PMID- 27254086 TI - Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study. AB - The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy. PMID- 27254087 TI - Substance Use and Misuse: Emerging Epidemiological Trends, New Definitions, and Innovative Treatment Targets. PMID- 27254088 TI - Epidemiology of Injection Drug Use: New Trends and Prominent Issues. AB - After more than 30 years of research, numerous studies have shown that injection drug use is associated with a wide range of adverse health outcomes such as drug overdoses, drug-related suicidal behaviours, comorbid psychiatric disorders, bloodborne pathogens and other infectious diseases, and traumas. This review explores new trends and prominent issues associated with injection drug use. The dynamic nature of injection drug use is underlined by examining its recent trends and changing patterns in Canada and other "high-income countries." Three research topics that could further contribute to the development of comprehensive prevention and intervention strategies aimed at people who inject drugs are also discussed: risk behaviours associated with the injection of prescription opioids, binge injection drug use, and mental health problems as determinants of injection risk behaviours. PMID- 27254090 TI - Mental Health Literacy: Past, Present, and Future. PMID- 27254089 TI - Alcohol Effects on Stress Pathways: Impact on Craving and Relapse Risk. AB - A significant amount of neurobiological research regarding the development of alcohol use disorders (AUDs) has focused on alcohol-related activation and long term alterations in the mesocortical dopaminergic reward pathways. However, alcohol does not only interact with brain reward systems. Many of its acute and chronic effects may be related to allostatic adaptations in hypothalamic and extrahypothalamic stress regulation pathways. For example, acute binge intoxication is associated with hypothalamically driven increases in blood cortisol, norepinephrine, and sex steroid metabolite levels. This may contribute to the development of mesocortical sensitization to alcohol. Furthermore, chronic alcohol exposure is associated with systemic dysregulation of the hypothalamic pituitary adrenal axis, sympathetic adrenal medullary system, and sex steroid systems. This dysregulation appears to manifest as neuroendocrine tolerance. In this review, we first summarize the literature suggesting that alcohol-induced alterations in these hypothalamic systems influence craving and contribute to the development of AUDs. We note that for women, the effects of alcohol on these neuroendocrine stress regulation systems may be influenced by the rhythmic variations of hormones and steroids across the menstrual cycle. Second, we discuss how changes in these systems may indicate progression of AUDs and increased risk of relapse in both sexes. Specifically, neuroendocrine tolerance may contribute to mesocortical sensitization, which in turn may lead to decreased prefrontal inhibitory control of the dopaminergic reward and hypothalamic stress systems. Thus, pharmacological strategies that counteract alcohol-associated changes in hypothalamic and extrahypothalamic stress regulation pathways may slow the development and progression of AUDs. PMID- 27254091 TI - Using Evolutionary Theory to Guide Mental Health Research. AB - Evolutionary approaches to medicine can shed light on the origins and etiology of disease. Such an approach may be especially useful in psychiatry, which frequently addresses conditions with heterogeneous presentation and unknown causes. We review several previous applications of evolutionary theory that highlight the ways in which psychiatric conditions may persist despite and because of natural selection. One lesson from the evolutionary approach is that some conditions currently classified as disorders (because they cause distress and impairment) may actually be caused by functioning adaptations operating "normally" (as designed by natural selection). Such conditions suggest an alternative illness model that may generate alternative intervention strategies. Thus, the evolutionary approach suggests that psychiatry should sometimes think differently about distress and impairment. The complexity of the human brain, including normal functioning and potential for dysfunctions, has developed over evolutionary time and has been shaped by natural selection. Understanding the evolutionary origins of psychiatric conditions is therefore a crucial component to a complete understanding of etiology. PMID- 27254092 TI - Identifying Trajectories of Borderline Personality Features in Adolescence: Antecedent and Interactive Risk Factors. AB - OBJECTIVE: To examine trajectories of adolescent borderline personality (BP) features in a normative-risk cohort (n = 566) of Canadian children assessed at ages 13, 14, 15, and 16 and childhood predictors of trajectory group membership assessed at ages 8, 10, 11, and 12. METHOD: Data were drawn from the McMaster Teen Study, an on-going study examining relations among bullying, mental health, and academic achievement. Participants and their parents completed a battery of mental health and peer relations questionnaires at each wave of the study. Academic competence was assessed at age 8 (Grade 3). Latent class growth analysis, analysis of variance, and logistic regression were used to analyze the data. RESULTS: Three distinct BP features trajectory groups were identified: elevated or rising, intermediate or stable, and low or stable. Parent- and child reported mental health symptoms, peer relations risk factors, and intra individual risk factors were significant predictors of elevated or rising and intermediate or stable trajectory groups. Child-reported attention-deficit hyperactivity disorder (ADHD) and somatization symptoms uniquely predicted elevated or rising trajectory group membership, whereas parent-reported anxiety and child-reported ADHD symptoms uniquely predicted intermediate or stable trajectory group membership. Child-reported somatization symptoms was the only predictor to differentiate the intermediate or stable and elevated or rising trajectory groups (OR 1.15, 95% CI 1.04 to 1.28). Associations between child reported reactive temperament and elevated BP features trajectory group membership were 10.23 times higher among children who were bullied, supporting a diathesis-stress pathway in the development of BP features for these youth. CONCLUSIONS: Findings demonstrate the heterogeneous course of BP features in early adolescence and shed light on the potential prodromal course of later borderline personality disorder. PMID- 27254093 TI - Employer Best Practice Guidelines for the Return to Work of Workers on Mental Disorder-Related Disability Leave: A Systematic Review. AB - OBJECTIVE: There has been an increasing number of employer best practice guidelines (BPGs) for the return to work (RTW) from mental disorder-related disability leave. This systematic review addresses 2 questions: 1) What is the quality of the development and recommendations of these BPGs? and 2) What are the areas of agreement and discrepancy among the identified guidelines related to the RTW from mental illness-related disability leave? METHOD: A systematic literature search was performed using publically available grey literature and best practice portals. It focused on the RTW of workers with medically certified disability leave related to mental disorders. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) was used to assess the quality of the development and recommendations of these BPGs. RESULTS: A total of 58 unique documents were identified for screening. After screening, 5 BPGs were appraised using AGREE II; 3 BPGs were included in the final set. There were no discrepancies among the 3, although they were from different countries. They all agreed there should be: 1) well-described organizational policies and procedures for the roles and responsibilities of all stakeholders, 2) a disability leave plan, and 3) work accommodations. In addition, one guideline suggested supervisor training and mental health literacy training for all staff. CONCLUSION: Although there were no discrepancies among the 3 BPGs, they emphasized different aspects of RTW and could be considered to be complementary. Together, they provide important guidance for those seeking to understand employer best practices for mental illness-related disability. PMID- 27254096 TI - The CaregiverVoice Survey: A Pilot Study Surveying Bereaved Caregivers To Measure the Caregiver and Patient Experience at End of Life. AB - OBJECTIVE: To integrate patient and caregiver feedback into end-of-life (EOL) care improvement, we tested the feasibility of a standardized, common instrument to measure care experiences across multiple settings in the last three months of life. METHODS: We developed and tested a survey, called the CaregiverVoice survey, which combined two validated questionnaires, the FAMCARE-2 and VOICES-SF. A retrospective, observational design was used to survey bereaved caregivers of decedents who had received homecare services in Ontario, Canada. RESULTS: In total, 330 surveys were completed (overall response rate of 13%, regional rates ranged from 4% to 83%). There was less than 5% missing data. Most patients received care from multiple settings in the last three months of life, including 60% for which a hospital stay was reported. The overall mean of the 19 FAMCARE-2 items was 1.7 (SD 0.7), with 72% of ratings as 1 very satisfied to 2 satisfied. On VOICES-SF items, 6% of respondents rated "all end-of-life services" as fair or poor, 24% as good, and 70% as excellent or outstanding, with variation depending on care site rated. 13% of caregivers reported that pain management was fair or poor in the last week of life. CONCLUSIONS: This pilot study provides preliminary evidence that it is feasible to capture the patient and caregiver experience at EOL using a comprehensive survey, though survey distribution method greatly affected response rates. The majority of responses rated care as excellent or very good, although several specific areas for improvement were identified. PMID- 27254094 TI - Early Intervention for Psychosis in Canada: What Is the State of Affairs? AB - OBJECTIVE: Early intervention services (EIS) for psychosis have been developed in several countries, including Canada. There is some agreement about the program elements considered essential for improving the long-term outcomes for patients in the early phase of psychotic disorders. In the absence of national standards, the current state of EIS for psychosis in Canada needs to be examined in relation to expert recommendations currently available. METHOD: A detailed online benchmark survey was developed and administered to 11 Canadian academic EIS programs covering administrative, clinical, education, and research domains. In addition, an electronic database and Internet search was conducted to find existing guidelines for EIS. Survey results were then compared with the existing expert recommendations. RESULTS: Most of the surveyed programs offer similar services, in line with published expert recommendations (i.e., easy and rapid access, intensive follow-up through case management with emphasis on patient engagement and continuity of care, and a range of integrated evidence-based psychosocial interventions). However, differences are observed among programs in admission and discharge criteria, services for patients at ultra high risk (UHR) for psychosis, patient to clinician ratios, accessibility of services, and existence of specific inpatient units. These seem to diverge from expert recommendations. CONCLUSIONS: Although Canadian programs are following most expert recommendations on clinical components of care, some programs lack administrative and organizational elements considered essential. Continued mentoring and networking of clinicians through organizations such as the Canadian Consortium for Early Intervention in Psychosis (CCEIP), as well as the development of a fidelity scale through further research, could possibly help programs attain and maintain the best standards of early intervention. However, simply making clinical guidelines available to care providers is not sufficient for changing practices; this will need to be accompanied by adequate funding and support from organizations and policy makers. PMID- 27254097 TI - Computational Studies on Cinchona Alkaloid-Catalyzed Asymmetric Organic Reactions. AB - Remarkable progress in the area of asymmetric organocatalysis has been achieved in the last decades. Cinchona alkaloids and their derivatives have emerged as powerful organocatalysts owing to their reactivities leading to high enantioselectivities. The widespread usage of cinchona alkaloids has been attributed to their nontoxicity, ease of use, stability, cost effectiveness, recyclability, and practical utilization in industry. The presence of tunable functional groups enables cinchona alkaloids to catalyze a broad range of reactions. Excellent experimental studies have extensively contributed to this field, and highly selective reactions were catalyzed by cinchona alkaloids and their derivatives. Computational modeling has helped elucidate the mechanistic aspects of cinchona alkaloid catalyzed reactions as well as the origins of the selectivity they induce. These studies have complemented experimental work for the design of more efficient catalysts. This Account presents recent computational studies on cinchona alkaloid catalyzed organic reactions and the theoretical rationalizations behind their effectiveness and ability to induce selectivity. Valuable efforts to investigate the mechanisms of reactions catalyzed by cinchona alkaloids and the key aspects of the catalytic activity of cinchona alkaloids in reactions ranging from pharmaceutical to industrial applications are summarized. Quantum mechanics, particularly density functional theory (DFT), and molecular mechanics, including ONIOM, were used to rationalize experimental findings by providing mechanistic insights into reaction mechanisms. B3LYP with modest basis sets has been used in most of the studies; nonetheless, the energetics have been corrected with higher basis sets as well as functionals parametrized to include dispersion M05-2X, M06-2X, and M06-L and functionals with dispersion corrections. Since cinchona alkaloids catalyze reactions by forming complexes with substrates via hydrogen bonds and long-range interactions, the use of split valence triple-zeta basis sets including diffuse and polarization functions on heavy atoms and polarization functions on hydrogens are recommended. Most of the studies have used the continuum-based models to mimic the condensed phase in which organocatalysts function; in some cases, explicit solvation was shown to yield better quantitative agreement with experimental findings. The conformational behavior of cinchona alkaloids is also highlighted as it is expected to shed light on the origin of selectivity and pave the way to a comprehensive understanding of the catalytic mechanism. The ultimate goal of this Account is to provide an up-to-date overlook on cinchona alkaloid catalyzed chemistry and provide insight for future studies in both experimental and theoretical fields. PMID- 27254098 TI - Single dose treatment of malaria - current status and perspectives. AB - INTRODUCTION: Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. AREAS COVERED: Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns. PMID- 27254099 TI - Intolerance of Uncertainty: A Temporary Experimental Induction Procedure. AB - BACKGROUND AND OBJECTIVES: Intolerance of uncertainty (IU) is a trans-diagnostic construct involved in anxiety and related disorders. Research focused on cross sectional reporting, manipulating attitudes toward objective and impersonal events or on treatments designed to reduce IU in clinical populations. The current paper presents an experimental procedure for laboratory manipulations of IU and tests mediation hypotheses following the Intolerance of Uncertainty Model. METHODS: On pre-test, undergraduate volunteers (Study 1, n = 43;68% women. Study 2, n = 169;83.8% women) were asked to provide an idiosyncratic future negative life event. State-IU, Worry, Positive and Negative Affect were assessed after that a standardized procedure was used to identify event's potential negative consequences. The same variables were assessed on post-test, after that participants were asked to read-through increasing and decreasing IU statements. RESULTS: Temporary changes on IU were consistently reproduced in both studies. Participants receiving increasing IU instructions reported greater state-IU, Worry and Negative Affect than those receiving decreasing IU instructions. However, this latter condition was not different from a control one (Study 2). Both studies revealed significant indirect effects of IU induction instructions on Worry and Negative Affect through state-IU. LIMITATIONS: Both studies used undergraduate psychology students samples, younger than average population and predominantly female. Experimental manipulation and outcome measures belongs to the same semantic domain, uncertainty, potentially limiting generalizability. CONCLUSIONS: Results supported the feasibility and efficacy of the proposed IU manipulation for non-clinical sample. Findings parallel clinical research showing that state-IU preceded Worry and Negative Affect states. PMID- 27254100 TI - The Snow Must Go On: Ground Ice Encasement, Snow Compaction and Absence of Snow Differently Cause Soil Hypoxia, CO2 Accumulation and Tree Seedling Damage in Boreal Forest. AB - At high latitudes, the climate has warmed at twice the rate of the global average with most changes observed in autumn, winter and spring. Increasing winter temperatures and wide temperature fluctuations are leading to more frequent rain on-snow events and freeze-thaw cycles causing snow compaction and formation of ice layers in the snowpack, thus creating ice encasement (IE). By decreasing the snowpack insulation capacity and restricting soil-atmosphere gas exchange, modification of the snow properties may lead to colder soil but also to hypoxia and accumulation of trace gases in the subnivean environment. To test the effects of these overwintering conditions changes on plant winter survival and growth, we established a snow manipulation experiment in a coniferous forest in Northern Finland with Norway spruce and Scots pine seedlings. In addition to ambient conditions and prevention of IE, we applied three snow manipulation levels: IE created by artificial rain-on-snow events, snow compaction and complete snow removal. Snow removal led to deeper soil frost during winter, but no clear effect of IE or snow compaction done in early winter was observed on soil temperature. Hypoxia and accumulation of CO2 were highest in the IE plots but, more importantly, the duration of CO2 concentration above 5% was 17 days in IE plots compared to 0 days in ambient plots. IE was the most damaging winter condition for both species, decreasing the proportion of healthy seedlings by 47% for spruce and 76% for pine compared to ambient conditions. Seedlings in all three treatments tended to grow less than seedlings in ambient conditions but only IE had a significant effect on spruce growth. Our results demonstrate a negative impact of winter climate change on boreal forest regeneration and productivity. Changing snow conditions may thus partially mitigate the positive effect of increasing growing season temperatures on boreal forest productivity. PMID- 27254101 TI - Cuboctahedron-based indium-organic frameworks for gas sorption and selective cation exchange. AB - [Me2NH2]3[In3(BTB)4].2DMF.2DMA.28H2O (InOF-9) is an anionic indium-organic framework based on nanosized cuboctahedrons, which is sustained by tetrahedral [In(COO)4] nodes and 3-connected tricarboxylates. Although InOF-9 is structurally unstable when exposed to air, it exhibits excellent gas sorption capacity through a supercritical carbon dioxide activation process and selectively encapsulates guest methylene blue cations. PMID- 27254102 TI - A new sequence for shaped voxel spectroscopy in the human brain using 2D spatially selective excitation and parallel transmission. AB - Spatially selective excitation in two dimensions (2D-SSE) utilizing parallel transmission was applied as a means to acquire signal from voxels adapted to the anatomy of interest for in vivo (1) H MR spectroscopy. A novel method to select spectroscopy voxels with arbitrary shapes in two dimensions was investigated. An on-off scheme with an adiabatic slice selective inversion pulse preceding a 2D SSE pulse together with a segmented inward spiral excitation k-space trajectory enabled rapid free induction decay acquisitions. Performance of the sequence was evaluated in simulations, phantom experiments, and in vivo measurements at 3 T. High spatial fidelity of the excitation profile was achieved for different target shapes and with little off-resonance deterioration. Metabolite concentrations in human brain determined with the new sequence were quantified with Cramer-Rao lower bounds less than 20%. They were in the physiological range and did not deviate systematically from results acquired with a conventional SPECIAL sequence. In conclusion, a new approach for shaped voxel MRS in the human brain is presented, which complements existing sequences. Simulations show that 2D-SSE pulses yield reduced chemical shift artifact when compared with conventional localization methods. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27254103 TI - Unexpected Fe-enriched compounds observed in Mg-Ce alloy: An atomic-scale STEM investigation. AB - This paper investigates into the unexpected nanosize Fe-enriched particles with defects incorporated, using EDS under STEM mode and atomic-resolution HAADF. The particle that locates between eutectic Mg12 Ce phase and alpha-Mg phase is identified as CeFe2 Si2 compound. Two types of defects are incorporated: Type-I defect is Ce-Si in a simple cubic lattice; Type-II defect is Ce in a FCC lattice. The interface between the defect-free CeFe2 Si2 and the defects is fully coherent. In addition, another two Ce/Fe/Si-enriched particles are observed, proving that the enrichment of Ce, Fe, and Si is not an accidental phenomenon. The observed formation of Ce/Fe/Si-enriched particles provides a possible explanation for the improvement in corrosion resistance and the purification effect induced by addition of rare earth elements into alloys. In addition, the present study demonstrates an advanced application of Cs-corrected HAADF by successfully directly imaging the dislocation and complex defects incorporated in the compound and by achieving a one-angstrom resolution. SCANNING 38:783-791, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27254104 TI - Special considerations in pregnant systemic sclerosis patients. AB - INTRODUCTION: Evaluating the fertility and pregnancy outcomes in systemic sclerosis (SSc) women is challenging. Studies are still limited or subject to potential methodological biases. Areas covered: This work is a comprehensive review of the literature. We discuss the potential impact of SSc on women's pregnancy outcomes and the effects of pregnancy on SSc. We summarize the physiological changes during pregnancy and describe our experience. Expert commentary: Although the miscarriage rate does not appear increased in SSc, women are exposed to a higher risk of premature birth and intrauterine growth restriction compared with the general population. Early diffuse cutaneous SSc and use of corticosteroids are risk factors, whereas folic acid use prevents against premature birth. All SSc women wishing to conceive should be counselled during a preconception visit. Physiological changes arising during pregnancy may be the source of clinical problems in SSc women with organs with limited capacities. PMID- 27254105 TI - Correction: Evaluating Subcriticality during the Ebola Epidemic in West Africa. AB - [This corrects the article DOI: 10.1371/journal.pone.0140651.]. PMID- 27254106 TI - Characterization of multiple nestin isoforms in the goldfish brain. AB - Nestin is an intermediate filament protein involved in neurogenesis in fish, mice, and humans. In this study we used rapid amplification of cDNA ends PCR to isolate goldfish nestin (nes). PCR analysis and sequencing revealed three different nes transcripts of 4003, 2446, and 2126 nucleotides, which are predicted to generate proteins of 860, 274, and 344 amino acids in length. Sequence analysis suggests that these nes transcripts are likely a result of alternative splicing. We next applied a multiple-antigenic peptide strategy to generate a goldfish-specific nestin antibody. Western blotting with this antibody together with mass spectrometry verified the presence of major nestin protein isoforms with differing molecular weights (~70, 40 and 30kDa). We further examined expression patterns of these nestin protein isoforms in different parts of the goldfish brain and pituitary and found the telencephalon to express all three isoforms at a distinct level and abundance. We report that multiple nestin isoforms are present indicating another level of complexity for the regulation of intermediate filaments in comparison to mammals. Studying the differential roles and regulation of these nestins could lead to a better understanding of cellular remodeling during neurogenesis and the unparalleled regenerative abilities after damage in the teleost CNS. PMID- 27254107 TI - Reduced Graphene Oxide-GelMA Hybrid Hydrogels as Scaffolds for Cardiac Tissue Engineering. AB - Biomaterials currently used in cardiac tissue engineering have certain limitations, such as lack of electrical conductivity and appropriate mechanical properties, which are two parameters playing a key role in regulating cardiac cell behavior. Here, the myocardial tissue constructs are engineered based on reduced graphene oxide (rGO)-incorporated gelatin methacryloyl (GelMA) hybrid hydrogels. The incorporation of rGO into the GelMA matrix significantly enhances the electrical conductivity and mechanical properties of the material. Moreover, cells cultured on composite rGO-GelMA scaffolds exhibit better biological activities such as cell viability, proliferation, and maturation compared to ones cultured on GelMA hydrogels. Cardiomyocytes show stronger contractility and faster spontaneous beating rate on rGO-GelMA hydrogel sheets compared to those on pristine GelMA hydrogels, as well as GO-GelMA hydrogel sheets with similar mechanical property and particle concentration. Our strategy of integrating rGO within a biocompatible hydrogel is expected to be broadly applicable for future biomaterial designs to improve tissue engineering outcomes. The engineered cardiac tissue constructs using rGO incorporated hybrid hydrogels can potentially provide high-fidelity tissue models for drug studies and the investigations of cardiac tissue development and/or disease processes in vitro. PMID- 27254109 TI - Combining Optimized Particle Morphology with a Niobium-Based Coating for Long Cycling-Life, High-Voltage Lithium-Ion Batteries. AB - Morphologically optimized LiNi0.5 Mn1.5 O4 (LMNO-0) particles were treated with LiNbO3 to prepare a homogeneously coated material (LMNO-Nb) as cathode in batteries. Graphite/LMNO-Nb full cells present a twofold higher cycling life than cells assembled using uncoated LMNO-0 (graphite/LMNO-0 cell): Graphite/LMNO-0 cells achieve 80 % of the initial capacity after more than 300 cycles whereas for graphite/LMNO-Nb cells this is the case for more than 600 cycles. Impedance spectroscopy measurements reveal significantly lower film and charge-transfer resistances for graphite/LMNO-Nb cells than for graphite/LMNO-0 cells during cycling. Reduced resistances suggest slower aging related to film thickening and increase of charge-transfer resistances when using LMNO-Nb cathodes. Tests at 45 degrees C confirm the good electrochemical performance of the investigated graphite/LMNO cells while the cycling stability of full cells is considerably lowered under these conditions. PMID- 27254108 TI - Low miR-187 expression promotes resistance to chemoradiation therapy in vitro and correlates with treatment failure in patients with esophageal adenocarcinoma. AB - Esophageal adenocarcinoma (EAC) has a poor prognosis and is increasing in incidence in many western populations. Neoadjuvant chemoradiation therapy (CRT) followed by surgery is increasingly the standard of care for locally advanced EAC; however, resistance to treatment is a significant clinical problem. The identification of both novel biomarkers predicting response to treatment and novel therapeutic targets to enhance the efficacy of CRT are key to improving survival rates in EAC. In this study we performed global microRNA (miRNA) profiling of pre-treatment EAC biopsies and identified 67 miRNA significantly altered in patients who are resistant to CRT. One of these miRNA, miR-187, was significantly decreased in pre-treatment EAC tumors from patients having a poor response to neoadjuvant CRT, highlighting downregulation of miR-187 as a potential mechanism of treatment resistance in EAC. In vitro, miR-187 was demonstrated to play a functional role in modulating sensitivity to X-ray radiation and cisplatin in EAC and its dysregulation was demonstrated to be due to chromosomal alterations. In vitro, miR-187 altered expression of a diverse array of pathways, including the immune regulator complement component 3 (C3), serum levels of which we have previously demonstrated to predict patient response to CRT. In vivo, expression of C3 was significantly increased in tumors from patients having a poor response to CRT. This study highlights for the first time a role for miR-187 as a novel biomarker of response to CRT and a potential therapeutic target for enhancing the efficacy of CRT in EAC. PMID- 27254110 TI - The influence of obesity and body mass index on the outcome of laparoscopic colorectal surgery: a systematic literature review. AB - AIM: The relationship between obesity, body mass index (BMI) and laparoscopic colorectal resection is unclear. Our object was to assess systematically the available evidence to establish the influence of obesity and BMI on the outcome of laparoscopic colorectal resection. METHOD: A search of PubMed/Medline databases was performed in May 2015 to identify all studies investigating the impact of BMI and obesity on elective laparoscopic colorectal resection performed for benign or malignant bowel disease. Clinical end-points examined included operation time, conversion rate to open surgery, postoperative complications including anastomotic leakage, length of hospital stay, readmission rate, reoperation rate and mortality. For patients who underwent an operation for cancer, the harvested number of lymph nodes and long-term oncological data were also examined. RESULTS: Forty-five studies were analysed, the majority of which were level IV with only four level III (Oxford Centre for Evidence-based Medicine 2011) case-controlled studies. Thirty comparative studies containing 23 649 patients including 17 895 non-obese and 5754 obese showed no significant differences between the two groups with respect to intra-operative blood loss, overall postoperative morbidity, anastomotic leakage, reoperation rate, mortality and the number of retrieved lymph nodes in patients operated on for malignancy. Most studies, including 15 non-comparative studies, reported a longer operation time in patients who underwent a laparoscopic procedure with the BMI being an independent predictor in multivariate analyses for the operation time. CONCLUSION: Laparoscopic colorectal resection is safe and technically and oncologically feasible in obese patients. These results, however, may vary outside of high volume centres of expertise. PMID- 27254112 TI - High-Temperature Monoclinic Cc Phase with Reduced c/a Ratio in Bi-based Perovskite Compound Bi2ZnTi1-xMnxO6. AB - Monoclinic phases with Cm, Pm, and Cc space groups are indispensable to understand the high performance of electromechanical properties at the morphotropic phase boundary (MPB) of lead-based perovskite oxides Pb(ZrxTi1-x)O3 (PZT), [Pb(Mg1/3Nb2/3)O3]1-x-(PbTiO3)x (PMN-PT), and [Pb(Zn1/3Nb2/3)O3]1-x (PbTiO3)x (PZN-PT). Here, a nearly single monoclinic phase with space group Cc was observed in the Bi-based lead-free perovskite compound Bi2ZnTi1-xMnxO6 at x = 0.4. This phase was the same as the low-temperature phase of the MPB composition of PZT but existed at a much higher temperature. Despite the reduced pseudo c/a ratio of 1.065, which is the same as that of PbTiO3 at room temperature, ionic model calculation based on the Rietveld refinement data indicated the polarization of Bi2ZnTi0.6Mn0.4O6 is 95.8 MUC/cm(2). The tilting and significant anisotropic distortion of the octahedron were found to cause the c/a ratio to reduce. Accordingly, the effective piezoelectric constant d33 of Bi2ZnTi0.6Mn0.4O6 thin film was found to be 12 pm/V. PMID- 27254113 TI - Missing Data in Alcohol Clinical Trials with Binary Outcomes. AB - BACKGROUND: Missing data are common in alcohol clinical trials for both continuous and binary end points. Approaches to handle missing data have been explored for continuous outcomes, yet no studies have compared missing data approaches for binary outcomes (e.g., abstinence, no heavy drinking days). This study compares approaches to modeling binary outcomes with missing data in the COMBINE study. METHODS: We included participants in the COMBINE study who had complete drinking data during treatment and who were assigned to active medication or placebo conditions (N = 1,146). Using simulation methods, missing data were introduced under common scenarios with varying sample sizes and amounts of missing data. Logistic regression was used to estimate the effect of naltrexone (vs. placebo) in predicting any drinking and any heavy drinking outcomes at the end of treatment using 4 analytic approaches: complete case analysis (CCA), last observation carried forward (LOCF), the worst case scenario (WCS) of missing equals any drinking or heavy drinking, and multiple imputation (MI). In separate analyses, these approaches were compared when drinking data were manually deleted for those participants who discontinued treatment but continued to provide drinking data. RESULTS: WCS produced the greatest amount of bias in treatment effect estimates. MI usually yielded less biased estimates than WCS and CCA in the simulated data and performed considerably better than LOCF when estimating treatment effects among individuals who discontinued treatment. CONCLUSIONS: Missing data can introduce bias in treatment effect estimates in alcohol clinical trials. Researchers should utilize modern missing data methods, including MI, and avoid WCS and CCA when analyzing binary alcohol clinical trial outcomes. PMID- 27254114 TI - The Association Between Anxiety Symptoms and Sleep in School-Aged Children: A Combined Insight From the Children's Sleep Habits Questionnaire and Actigraphy. AB - The current study assessed the association between anxiety symptoms and sleep in 90 school-aged children, aged 6-12 years (Mage = 108 months, 52.2% male). The Children's Sleep Habits Questionnaire (CSHQ) and 14 nights of actigraphy were used to assess sleep. Anxiety was assessed using the Spence Children's Anxiety Scale (SCAS). A significant association was found between parent-reported anxiety symptoms and current sleep problems (i.e., CSHQ total scores >= 41). An examination of SCAS subscales identified a specific association between generalized anxiety disorder (GAD) symptoms and increased parental sleep concerns, including sleep onset delay, sleep duration, and daytime sleepiness. Regarding actigraphy, whilst anxiety was not associated with average sleep variables, a relationship was identified between anxiety and the night-to-night variability of actigraphy-derived sleep schedules. PMID- 27254111 TI - Cognitive Impairments Induced by Concussive Mild Traumatic Brain Injury in Mouse Are Ameliorated by Treatment with Phenserine via Multiple Non-Cholinergic and Cholinergic Mechanisms. AB - Traumatic brain injury (TBI), often caused by a concussive impact to the head, affects an estimated 1.7 million Americans annually. With no approved drugs, its pharmacological treatment represents a significant and currently unmet medical need. In our prior development of the anti-cholinesterase compound phenserine for the treatment of neurodegenerative disorders, we recognized that it also possesses non-cholinergic actions with clinical potential. Here, we demonstrate neuroprotective actions of phenserine in neuronal cultures challenged with oxidative stress and glutamate excitotoxicity, two insults of relevance to TBI. These actions translated into amelioration of spatial and visual memory impairments in a mouse model of closed head mild TBI (mTBI) two days following cessation of clinically translatable dosing with phenserine (2.5 and 5.0 mg/kg BID x 5 days initiated post mTBI) in the absence of anti-cholinesterase activity. mTBI elevated levels of thiobarbituric acid reactive substances (TBARS), a marker of oxidative stress. Phenserine counteracted this by augmenting homeostatic mechanisms to mitigate oxidative stress, including superoxide dismutase [SOD] 1 and 2, and glutathione peroxidase [GPx], the activity and protein levels of which were measured by specific assays. Microarray analysis of hippocampal gene expression established that large numbers of genes were exclusively regulated by each individual treatment with a substantial number of them co-regulated between groups. Molecular pathways associated with lipid peroxidation were found to be regulated by mTBI, and treatment of mTBI animals with phenserine effectively reversed injury-induced regulations in the 'Blalock Alzheimer's Disease Up' pathway. Together these data suggest that multiple phenserine-associated actions underpin this compound's ability to ameliorate cognitive deficits caused by mTBI, and support the further evaluation of the compound as a therapeutic for TBI. PMID- 27254115 TI - Tropical amphibians in shifting thermal landscapes under land-use and climate change. AB - Land-cover and climate change are both expected to alter species distributions and contribute to future biodiversity loss. However, the combined effects of land cover and climate change on assemblages, especially at the landscape scale, remain understudied. Lowland tropical amphibians may be particularly susceptible to changes in land cover and climate warming because many species have narrow thermal safety margins resulting from air and body temperatures that are close to their critical thermal maxima (CTmax ). We examined how changing thermal landscapes may alter the area of thermally suitable habitat (TSH) for tropical amphibians. We measured microclimates in 6 land-cover types and CTmax of 16 frog species in lowland northeastern Costa Rica. We used a biophysical model to estimate core body temperatures of frogs exposed to habitat-specific microclimates while accounting for evaporative cooling and behavior. Thermally suitable habitat area was estimated as the portion of the landscape where species CTmax exceeded their habitat-specific maximum body temperatures. We projected changes in TSH area 80 years into the future as a function of land-cover change only, climate change only, and combinations of land-cover and climate-change scenarios representing low and moderate rates of change. Projected decreases in TSH area ranged from 16% under low emissions and reduced forest loss to 30% under moderate emissions and business-as-usual land-cover change. Under a moderate emissions scenario (A1B), climate change alone contributed to 1.7- to 4.5-fold greater losses in TSH area than land-cover change only, suggesting that future decreases in TSH from climate change may outpace structural habitat loss. Forest restricted species had lower mean CTmax than species that occurred in altered habitats, indicating that thermal tolerances will likely shape assemblages in changing thermal landscapes. In the face of ongoing land-cover and climate change, it will be critical to consider changing thermal landscapes in strategies to conserve ectotherm species. PMID- 27254116 TI - Weight-related stigma is a significant psychosocial stressor in developing countries: Evidence from Guatemala. AB - Weight-related stigma is established as a major psychosocial stressor and correlate of depression among people living with obesity in high-income countries. Anti-fat beliefs are rapidly globalizing. The goal of the study is to (1) examine how weight-related stigma, enacted as teasing, is evident among women from a lower-income country and (2) test if such weight-related stigma contributes to depressive symptoms. Modeling data for 12,074 reproductive-age women collected in the 2008-2009 Guatemala National Maternal-Infant Health Survey, we demonstrate that weight-related teasing is (1) experienced by those both underweight and overweight, and (2) a significant psychosocial stressor. Effects are comparable to other factors known to influence women's depressive risk in lower-income countries, such as living in poverty, experiencing food insecurity, or suffering sexual/domestic violence. That women's failure to meet local body norms-whether they are overweight or underweight-serves as such a strong source of psychological distress is particularly concerning in settings like Guatemala where high levels of over- and under-nutrition intersect at the household and community level. Current obesity-centric models of weight-related stigma, developed from studies in high-income countries, fail to recognize that being underweight may create similar forms of psychosocial distress in low-income countries. PMID- 27254117 TI - Accommodative Anomalies in a Sample of Black High School Students in South Africa. AB - PURPOSE: Accommodative anomalies cause asthenopia and affect student reading efficiency and academic performance. The aim of conducting this study was to determine the prevalence and distribution of accommodative anomalies (insufficiency, excess and infacility) in relation to demographic variables (sex, age, school grade level and study location). METHODS: Study participants comprised 1,211 children (481 male and 730 female), with age range 13-19 years. Visual functions evaluated included refractive error, accommodative amplitude, accuracy, facility and relative accommodation. RESULTS: A total of 242 participants (20.2%) had accommodative anomalies. Prevalence estimates were; accommodative infacility 12.9% (95% confidence interval, CI, 10.9-14.7%), accommodative insufficiency 4.5% (95% CI 3.4-5.8%) and accommodative excess 2.8% (95% CI 1.9-3.8%). There were no significant differences based on sex, school grade level or study site, except in the prevalence of accommodative infacility, which was significantly higher in the younger grade level than the older (P=0.027). CONCLUSION: The study fills a gap in the literature in providing data on predominantly black South African students. The prevalence estimates for accommodative insufficiency and excess found in the sample studied are relatively low, while that of accommodative infacility is high. Accommodative anomalies were not markedly associated with demographic variables except for the prevalence of accommodative infacility, which was significantly higher in the younger grade level than the older. Identification and referral are important steps towards diagnosis and treatment of accommodative anomalies. Future studies on differences in prevalence of accommodative anomalies among different racial populations will be relevant. PMID- 27254131 TI - Carbon Monoxide: A Mild and Efficient Reducing Agent towards Atomically Precise Gold Nanoclusters. AB - In recent years, thiolate-protected gold nanoclusters (or thiolated Au NCs) with a core size below 2 nm have emerged as a new class of multifunctional nanoparticles because of their unique molecular-like properties and the potential to use these properties in many practical applications. A general synthesis of Au NCs may involve the use of a strong reducing agent (e.g., sodium borohydride (NaBH4 )), which often leads to the formation of mix-sized Au NCs if no delicate control is applied. To obtain atomically precise Au NCs, additional physical or chemical selection processes (e.g., high-resolution separation or size-focusing) are required, which are difficult to be scaled up or are limited to only thermodynamically stable products. By introducing a milder reducing agent - carbon monoxide (CO) - both stable and metastable thiolated Au NCs, including Au10-12 , Au15 , Au18 , Au25 , and Au29 , can be synthesized in a one-pot manner. In addition, CO reduction also enables the synthesis of a highly luminescent Au22 (SG)18 NC. Furthermore, the intermediates of Au NC growth can be tracked in the CO-reduction system due to the mild and readily stoppable nature of CO reduction. Therefore, the use of CO reduction may bring new flexibilities in designing synthetic strategies and understanding the growth mechanism of atomically precise Au NCs, which could contribute to a better design of functional Au NCs, further paving their way towards practical applications in various fields. PMID- 27254118 TI - RNA-Seq reveals 10 novel promising candidate genes affecting milk protein concentration in the Chinese Holstein population. AB - Paired-end RNA sequencing (RNA-Seq) was used to explore the bovine transcriptome from the mammary tissue of 12 Chinese Holstein cows with 6 extremely high and 6 low phenotypic values for milk protein percentage. We defined the differentially expressed transcripts between the two comparison groups, extremely high and low milk protein percentage during the peak lactation (HP vs LP) and during the non lactating period (HD vs LD), respectively. Within the differentially expressed genes (DEGs), we detected 157 at peak lactation and 497 in the non-lactating period with a highly significant correlation with milk protein concentration. Integrated interpretation of differential gene expression indicated that SERPINA1, CLU, CNTFR, ERBB2, NEDD4L, ANG, GALE, HSPA8, LPAR6 and CD14 are the most promising candidate genes affecting milk protein concentration. Similarly, LTF, FCGR3A, MEGF10, RRM2 and UBE2C are the most promising candidates that in the non-lactating period could help the mammary tissue prevent issues with inflammation and udder disorders. Putative genes will be valuable resources for designing better breeding strategies to optimize the content of milk protein and also to provide new insights into regulation of lactogenesis. PMID- 27254132 TI - Effectiveness of airway clearance techniques in children hospitalized with acute bronchiolitis. AB - OBJECTIVE: To evaluate the effectiveness of two airway clearance techniques (ACT's) in children <24 months hospitalized with mild to moderate bronchiolitis. DESIGN: One hundred and three children were randomly allocated to receive one 20 min session daily, either assisted autogenic drainage (AAD), intrapulmonary percussive ventilation (IPV), or bouncing (B) (control group), ninety-three finished the study. OUTCOME MEASURES: Mean time to recovery in days was our primary outcome measure. The impact of the treatment and the daily improvement was also assessed by a validated clinical and respiratory severity score (WANG score), heart rate (HR), and oxygen saturation (SaO2 ). RESULTS: Mean time to recovery was 4.5 +/- 1.9 days for the control group, 3.6 +/- 1.4 days, P < 0.05 for the AAD group and 3.5 +/- 1.3 days, P = 0.03 for the IPV group. Wang scores improved significantly for both physiotherapy techniques compared to the control group. CONCLUSION: Both ACT's reduced significantly the length of hospital stay compared to no physiotherapy. Pediatr Pulmonol. 2017;52:225-231. (c) 2016 Wiley Periodicals, Inc. PMID- 27254133 TI - Carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients. AB - AIM: Supplementation with levocarnitine preparations has been reported to improve hepatic encephalopathy, but no detailed investigations have addressed the dynamics of carnitine or its supplementation indication in cirrhosis patients. We studied carnitine dynamics in cirrhotic patients by measuring serum and liver tissue carnitine levels and tested the effects of levocarnitine supplementation on concurrent hyperammonemia. METHODS: In a pilot cohort of seven patients with liver cirrhosis and five patients without cirrhosis, the serum and liver carnitine concentrations were measured. Then the serum carnitine fractions were analyzed in 70 liver cirrhosis patients. Among them, a levocarnitine preparation (1800 mg/day) was supplemented orally for 3 months in 27 patients with refractory hyperammonemia, and the effects were evaluated. RESULTS: A significant correlation was observed between serum and liver tissue carnitine concentrations (r = 0.69, P < 0.05). The serum total carnitine concentration was 68.4 +/- 4.7 MUmol/L, the free carnitine concentration was 53.2 +/- 2.6 MUmol/L, and the acylcarnitine concentration was 13.2 +/- 1.1 MUmol/L in 70 cirrhotic patients (reference values are 45-91, 36-74, 6-23 MUmol/L, respectively). There was no correlation between blood ammonia and serum carnitine concentrations. The serum carnitine concentration rose with levocarnitine supplementation, reaching steady state after 1 month and, in parallel, refractory hyperammonemia was significantly improved. The cut-off level for a 20% decrease in blood ammonia was identified as 62.0 MUmol/L total carnitine concentration by receiver-operating characteristic curve analysis, with an area under the curve of 0.69. CONCLUSION: Serum carnitine concentrations were within standard levels in the majority of liver cirrhosis patients. In patients with concurrent hyperammonemia, the levocarnitine supplementation reduced blood ammonia levels. PMID- 27254134 TI - End of Frustration: Catalytic Precision Polymerization with Highly Interacting Lewis Pairs. AB - Herein we report on the catalytic polymerization of diverse Michael-type monomers with high precision by using simple but highly active combinations of phosphorus containing Lewis bases and organoaluminum compounds. The interacting Lewis pair catalysts enable the control of molecular weight and microstructure of the produced polymers. The reactions show a linear Mn vs consumption plot thus proving a living type polymerization. The initiation has been investigated by end group analysis with ESI mass spectrometric analysis. With these main-group element Lewis acid base pairs, it is not only possible to polymerize sterically demanding, functionalized as well as heteroatom containing monomers but also, for the first time, to catalytically polymerize extended Michael systems, like 4 vinylpyridine. PMID- 27254135 TI - Accelerated Aging in Bone Marrow Transplant Survivors. PMID- 27254136 TI - Influence of film structure on the dewetting kinetics of thin polymer films in the solvent annealing process. AB - On a non-wetting solid substrate, the solvent annealing process of a thin polymer film includes the swelling process and the dewetting process. Owing to difficulties in the in situ analysis of the two processes simultaneously, a quantitative study on the solvent annealing process of thin polymer films on the non-wetting solid substrate is extremely rare. In this paper, we design an experimental method by combining spectroscopic ellipsometry with optical microscopy to achieve the simultaneous in situ study. Using this method, we investigate the influence of the structure of swollen film on its dewetting kinetics during the solvent annealing process. The results show that for a thin PS film with low Mw (Mw = 4.1 kg mol(-1)), acetone molecules can form an ultrathin enriched layer between the PS film and the solid substrate during the swelling process. The presence of the acetone enriched layer accounts for the exponential kinetic behavior in the case of a thin PS film with low Mw. However, the acetone enriched layer is not observed in the case of a thin PS film with high Mw (Mw = 400 kg mol(-1)) and the slippage effect of polymer chains is valid during the dewetting process. PMID- 27254137 TI - Short Enantioselective Total Syntheses of trans-Clerodane Diterpenoids: Convergent Fragment Coupling Using a trans-Decalin Tertiary Radical Generated from a Tertiary Alcohol Precursor. AB - The evolution of a convergent fragment-coupling strategy for the enantioselective total synthesis of trans-clerodane diterpenoids is described. The key bond construction is accomplished by 1,6-addition of a trans-decalin tertiary radical with 4-vinylfuran-2-one. The tertiary radical is optimally generated from the hemioxalate salt of the corresponding tertiary alcohol upon activation by visible light and an Ir(III) photoredox catalyst. The enantioselective total synthesis of trans-clerodane diterpenoid 1 reported here was accomplished in seven steps from 3-methyl-2-cyclohexenone. The synthetic strategy described in this report allows a number of trans-clerodane diterpenoids to be synthesized in enantioselective fashion by synthetic sequences of 10 steps or less. This study illustrates a powerful tactic in organic synthesis in which a structurally complex target structure is disconnected at a quaternary carbon stereocenter to fragments of comparable complexity, which are united in the synthetic pathway by conjugate addition of a nucleophilic tertiary radical to a fragment harboring an electron deficient C-C double bond. PMID- 27254138 TI - Usefulness of an angioplasty balloon as selective bronchial blockade device after transbronchial cryobiopsy. AB - BACKGROUND AND OBJECTIVE: Transbronchial cryobiopsy (TBCB) is a technique in which frozen samples of lung are obtained using a probe inserted through a bronchoscope. We performed a retrospective study to assess the performance of the TBCB procedure complemented by segmental bronchial blockade using an angioplasty balloon, in terms of diagnostic yield and safety in diffuse parenchymal lung disease (DPLD). METHODS: Data from 100 patients with suspected DPLD (clinical and radiological findings), who underwent TBCB in our institution to establish a definitive diagnosis, were reviewed. In our institution, TBCB is monitored with fluoroscopy and performed under general anaesthesia by a multidisciplinary team (an anaesthesiologist, a pulmonologist and an interventional radiologist). In each patient, four samples were collected using a 2.4-mm distal diameter cryoprobe. To control bleeding, the biopsied segmental bronchus was blocked with a 6-mm diameter angioplasty balloon, inserted over a 0.035-inch angled hydrophilic guidewire. After the cryoextraction, the balloon was inflated for 3 min intervals until bleeding stopped. RESULTS: Overall, 98% of samples had diagnostic value. In 85% of cases, DPLD was confirmed, while in 7%, cancer was diagnosed. Complications were observed in 16% of the patients: 13 patients developed moderate haemorrhage, and 3 developed pneumothorax. CONCLUSION: Transbronchial cryobiopsy had a high diagnostic yield for DPLD. Performing the procedure under fluoroscopy guidance and using angioplasty balloon for selective bronchial blockade achieved a low rate of iatrogenic complications directly associated with the technique. PMID- 27254139 TI - Enzymatic synthesis of novel oligosaccharides from N-acetylsucrosamine and melibiose using Aspergillus niger alpha-galactosidase, and properties of the products. AB - Two kinds of oligosaccharides, N-acetylraffinosamine (RafNAc) and N acetylplanteosamine (PlaNAc), were synthesized from N-acetylsucrosamine and melibiose using the transgalactosylation activity of Aspergillus niger alpha galactosidase. RafNAc and PlaNAc are novel trisaccharides in which d glucopyranose residues in raffinose (Raf) and planteose are replaced with N acetyl-d-glucosamine. These trisaccharides were more stable in acidic solution than Raf. RafNAc was hydrolyzed more rapidly than Raf by alpha-galactosidase of green coffee bean. In contrast, RafNAc was not hydrolyzed by Saccharomyces cerevisiae invertase, although Raf was hydrolyzed well by this enzyme. These results indicate that the physicochemical properties and steric structure of RafNAc differ considerably from those of Raf. PMID- 27254141 TI - From pregnancy to childhood and adulthood: the trajectory of hypertension. PMID- 27254140 TI - Defense Meteorological Satellite Program data should no longer be used for epidemiological studies. PMID- 27254142 TI - Validation of noninvasive devices for central blood pressure assessment: a yet unresolved issue. PMID- 27254143 TI - Flavanol-rich cocoa at breakfast: the right remedy after a sleepless night to prevent negative effects on blood pressure and cognition? PMID- 27254144 TI - Blood pressure phenotypes in youth: advances in the application of central aortic pressure. PMID- 27254145 TI - Depression in hypertensive patients: the role of comorbidities. PMID- 27254146 TI - Reply. PMID- 27254147 TI - Mechanisms underlying elevated SBP differ with adiposity in young adults: the Enigma study. PMID- 27254148 TI - Reply. PMID- 27254149 TI - Blood pressure goals revisited. PMID- 27254150 TI - Food Neophobia in Wild Rats (Rattus norvegicus) Inhabiting a Changeable Environment-A Field Study. AB - Food neophobia is a reaction to novel food observed in many animal species, particularly omnivores, including Rattus norvegicus. A neophobic reaction is typically characterised by avoidance of novel food and the necessity to assess both its potential value and toxicity by the animal. It has been hypothesised that this reaction is not observed in rats inhabiting a changeable environment with a high level of variability with regard to food and food sources. This study was conducted in such changeable conditions and it aims to demonstrate the behaviour of wild rats R. norvegicus in their natural habitat. The rats were studied in a farm setting, and the experimental arena was demarcated by a specially constructed pen which was freely accessible to the rats. At regular intervals, the rats were given new flavour- and smell-altered foods, while their behaviour was video-recorded. The results obtained in the study seem to confirm the hypothesis that rats inhabiting a highly changeable environment do not exhibit food neophobia. The observed reaction to novel food may be connected with a reaction to a novel object to a larger extent than to food neophobia. The value of the results obtained lies primarily in the fact that the study was conducted in the animals' natural habitat, and that it investigated their spontaneous behaviours. PMID- 27254151 TI - Population Estimation Using a 3D City Model: A Multi-Scale Country-Wide Study in the Netherlands. AB - The remote estimation of a region's population has for decades been a key application of geographic information science in demography. Most studies have used 2D data (maps, satellite imagery) to estimate population avoiding field surveys and questionnaires. As the availability of semantic 3D city models is constantly increasing, we investigate to what extent they can be used for the same purpose. Based on the assumption that housing space is a proxy for the number of its residents, we use two methods to estimate the population with 3D city models in two directions: (1) disaggregation (areal interpolation) to estimate the population of small administrative entities (e.g. neighbourhoods) from that of larger ones (e.g. municipalities); and (2) a statistical modelling approach to estimate the population of large entities from a sample composed of their smaller ones (e.g. one acquired by a government register). Starting from a complete Dutch census dataset at the neighbourhood level and a 3D model of all 9.9 million buildings in the Netherlands, we compare the population estimates obtained by both methods with the actual population as reported in the census, and use it to evaluate the quality that can be achieved by estimations at different administrative levels. We also analyse how the volume-based estimation enabled by 3D city models fares in comparison to 2D methods using building footprints and floor areas, as well as how it is affected by different levels of semantic detail in a 3D city model. We conclude that 3D city models are useful for estimations of large areas (e.g. for a country), and that the 3D approach has clear advantages over the 2D approach. PMID- 27254152 TI - Upper Airway Computed Tomography Measures and Receipt of Tracheotomy in Infants With Robin Sequence. AB - IMPORTANCE: Airway management in infants with Robin sequence is challenging. Objective upper airway measures associated with severe airway compromise requiring tracheotomy are needed to guide decision making. OBJECTIVES: To define objective upper airway measures in infants with Robin sequence from craniofacial computed tomography (CT) and to identify those measures in Robin sequence associated with tracheotomy. DESIGN, SETTING, AND PARTICIPANTS: A cohort study (2003 to 2014, over 1-year follow-up) of 37 infants with Robin sequence evaluated for surgical management and 37 selected age- and sex-matched controls without a craniofacial condition conducted in a pediatric institution's craniofacial center. MAIN OUTCOMES AND MEASURES: Define and compare CT-generated upper airway measures in these groups: infants with Robin sequence vs controls, and infants with Robin sequence with vs without tracheotomy. A negative difference signifies lower values for the Robin sequence and tracheotomy groups. Clinical data collected included age and height at time of CT scan, sex, tracheotomy presence, associated syndrome, and laboratory indicators of hypoventilation and hypoxemia. To evaluate interrater reliability, 2 raters performed each measurement in the Robin sequence group. RESULTS: In 74 infants, 17 of 28 measures were different between infants with Robin sequence and those in the control group. Tracheotomy was performed in 14 of 37 (38%) infants with Robin sequence. Infants with tracheotomy more commonly had associated syndromes (12 of 14 [86%] vs 11 of 23 [48%]) and a history of hypoventilation and hypoxemia (13 of 14 [93%] vs 15 of 23 [65%]). Five of the 11 measures associated with tracheotomy were reliable and simpler to measure with the following mean differences (95% CIs) between groups: tongue length, 0.87 (0.26 to 1.48); tongue position relative to palate, 0.83 (0.22 to 1.45); mandibular total length, -0.8 (-1.42 to -0.19); gonial angle, 0.71 (0.08 to 1.34); and inferior pogonial angle, 0.66 (0.02 to 1.29). Using a receiver operating characteristic analysis, a composite score of these 5 measures for predicting tracheotomy risk yielded an area under the curve of 0.83 and achieved 86% sensitivity and 74% specificity. CONCLUSIONS AND RELEVANCE: Computed tomography measures quantifying tongue position and mandibular configuration can identify infants with Robin sequence, and importantly, differentiate those who have severe upper airway compromise requiring tracheotomy. Following validation, these measures can be used for objective upper airway assessment and for expediting clinical decision-making in these challenging cases for which no such tools currently exist. PMID- 27254153 TI - Effects of aging and soil properties on zinc oxide nanoparticle availability and its ecotoxicological effects to the earthworm Eisenia andrei. AB - To assess the influence of soil properties and aging on the availability and toxicity of zinc (Zn) applied as nanoparticles (Zn oxide [ZnO]-NPs) or as Zn2+ ions (Zn chloride [ZnCl2 ]), 3 natural soils were individually spiked with either ZnO-NPs or ZnCl2 and incubated for up to 6 mo. Available Zn concentrations in soil were measured by porewater extraction (ZnPW), whereas earthworms (Eisenia andrei) were exposed to study Zn bioavailability. Porewater extraction concentrations were lower when Zn was applied as NPs compared to the ionic form and decreased with increasing soil pH. For both Zn forms and Zn-PW values were affected by aging, but they varied among the tested soils, highlighting the influence of soil properties. Internal Zn concentration in the earthworms (ZnE) was highest for the soil with high organic carbon content (5.4%) and basic pH (7.6) spiked with Zn-NPs, but the same soil spiked with ZnCl2 showed the lowest increase in ZnE compared to the control. Survival, weight change, and reproduction of the earthworms were affected by both Zn forms; but differences in toxicity could not be explained by soil properties or aging. This shows that ZnO NPs and ZnCl2 behave differently in soils depending on soil properties and aging processes, but differences in earthworm toxicity remain unexplained. Environ Toxicol Chem 2017;36:137-146. (c) 2016 SETAC. PMID- 27254154 TI - Supramolecular Photochemistry as a Potential Synthetic Tool: Photocycloaddition. AB - Photochemistry, bearing significant applications in natural and man-made events such as photosynthesis, vision, photolithography, photodynamic therapy, etc., is yet to become a common tool during the synthesis of small molecules in a laboratory. Among other rationale, the inability to influence photochemical reactions with temperature, solvent, additives, etc., dissuades chemists from employing light-initiated reactions as a routine synthetic tool. This review highlights how diverse, highly organized structures such as solvent-free crystals and water-soluble host-guest assemblies can be employed to control and manipulate photoreactions and thereby serve as an efficient tool for chemists, including those interested in synthesis. The efficacy of the media in modifying the excited state behavior of organic molecules is illustrated with photocycloaddition in general and [2 + 2] photocycloaddition in particular, reactions widely employed in the synthesis of complex natural products as well as highly constrained molecules, as exemplars. The reaction media, highly pertinent in the context of green sustainable chemistry, include solvent-free crystals and solids such as silica, clay, and zeolite and water-soluble hosts that can solubilize and preorganize hydrophobic reactants in water. Since no other reagent would be more sustainable than light and no other medium greener than water, we believe that the supramolecular photochemistry expounded here has a momentous role as a synthetic tool in the future. PMID- 27254155 TI - Water as the Key to Proto-Aragonite Amorphous CaCO3. AB - Temperature and pH value can affect the short-range order of proto-structured and additive-free amorphous calcium carbonates (ACCs). Whereas a distinct change occurs in proto-vaterite (pv) ACC above 45 degrees C at pH 9.80, proto-calcite (pc) ACC (pH 8.75) is unaffected within the investigated range of temperatures (7 65 degrees C). IR and NMR spectroscopic studies together with EXAFS analysis showed that the temperature-induced change is related to the formation of proto aragonite (pa) ACC. The data strongly suggest that the binding of water molecules induces dipole moments across the carbonate ions in pa-ACC as in aragonite, where the dipole moments are due to the symmetry of the crystal structure. Altogether, a (pseudo-)phase diagram of the CaCO3 polyamorphism in which water plays a key role can be formulated based on variables of state, such as the temperature, and solution parameters, such as the pH value. PMID- 27254156 TI - Intraoperative Visual Documentation Using Smart Mobile Devices: A Simple Solution for Facial Plastic Surgeons. PMID- 27254157 TI - Suppressing the Rayleigh-Plateau Instability in Field-Directed Colloidal Assembly. AB - Suspensions of superparamagnetic colloids that equilibrate in a toggled magnetic field undergo a Rayleigh-Plateau instability with a characteristic wavelength lambda = 600 MUm for the toggle frequency nu = 0.66 Hz. The instability is suppressed when the chamber length L in the field direction is less than 2lambda. The final size of the magnetic domains perpendicular to the field, D, follows a power law relation of D ~ L(0.71+/-0.07). These results demonstrate the structural differences of field-directed suspensions when confined to lengths scale set by the phase separation process and can potentially be used to create self-assembled colloidal crystals with well-defined size and shape. PMID- 27254158 TI - A Case of Carotid-Esophageal Fistula Masquerading as an Upper Gastrointestinal Bleed. PMID- 27254159 TI - Nucleophilic Nitration of Arynes by Sodium Nitrite and its Multicomponent Reaction Leading to Double-Functionalized Arenes. AB - An unusual nucleophilic nitration of arynes by NaNO2 in the presence of water has been developed, and the concept was further demonstrated to accomplish a double functionalization of arynes using a multicomponent reaction protocol to synthesize pharmaceutically important (2-nitrophenyl)methanol derivatives. Such substitution ortho to -NO2 is difficult by other means. The reaction conditions are mild and avoid the use of strong acids, expensive transition metal catalysts, and additives. PMID- 27254169 TI - Awareness of human papilloma virus and cervical cancer prevention among Greek female healthcare workers. AB - The incidence rate of cervical cancer varies by geographic region, with less developed regions showing the highest rates. All risk factors for cervical cancer are actually preventable if appropriate lifestyle changes are adopted. In addition, vaccines protecting against the majority of human papilloma virus (HPV) high-risk types have been developed. Even though cervical cancer is preventable, not all women are aware of this or how it can be prevented. Thus, it is essential for every nation to assess the level of knowledge among women of cervical cancer and HPV prevention. In this work, we assessed the level of awareness and attitudes of Greek female healthcare workers on cervical cancer and HPV prevention through the delivery of a validated questionnaire between March and June 2012 in three hospitals in Greece. Our results show that there exist gaps in the knowledge of women on this topic, especially in terms of the newest information on cervical cancer prevention through HPV testing and vaccination. In fact, only 80% of surveyed women knew about the existence of HPV testing. We propose that more information needs to be transmitted to Greek women and men on HPV testing and vaccination. Even though the incidence of cervical cancer is not extremely high in Greece, this number can easily change, especially in the face of the economic crisis and the increasing rates of migration, which can result in higher rates of HPV infection in the population if no measures for HPV prevention are implemented. PMID- 27254231 TI - Patient experience and quality of urologic cancer surgery in US hospitals. AB - BACKGROUND: Care interactions as perceived by patients and families are increasingly viewed as both an indicator and lever for high-value care. To promote patient-centeredness and motivate quality improvement, payers have begun tying reimbursement with related measures of patient experience. Accordingly, the authors sought to determine whether such data correlate with outcomes among patients undergoing surgery for genitourinary cancer. METHODS: The authors used the Nationwide Inpatient Sample and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) data from 2009 through 2011. They identified hospital admissions for cancer-directed prostatectomy, nephrectomy, and cystectomy, and measured mortality, hospitalization length, discharge disposition, and complications. Mixed effects models were used to compare the likelihood of selected outcomes between the top and bottom tercile hospitals adjusting for patient and hospital characteristics. RESULTS: Among a sample of 46,988 encounters, the authors found small differences in patient age, race, income, comorbidity, cancer type, receipt of minimally invasive surgery, and procedure acuity according to HCAHPS tercile (P<.001). Hospital characteristics also varied with respect to ownership, teaching status, size, and location (P<.001). Compared with patients treated in low-performing hospitals, patients treated in high-performing hospitals less often faced prolonged hospitalization (odds ratio, 0.77; 95% confidence interval, 0.64-0.92) or nursing-sensitive complications (odds ratio, 0.85; 95% confidence interval, 0.72-0.99). No difference was found with regard to inpatient mortality, other complications, and discharge disposition (P>.05). CONCLUSIONS: Using Nationwide Inpatient Sample and HCAHPS data, the authors found a limited association between patient experience and surgical outcomes. For urologic cancer surgery, patient experience may be optimally viewed as an independent quality domain rather than a mechanism with which to improve surgical outcomes. Cancer 2016;122:2571-8. (c) 2016 American Cancer Society. PMID- 27254232 TI - Contributing to Your Journal. PMID- 27254233 TI - How to Facilitate Change. PMID- 27254234 TI - LETTER FROM THE PRESIDENT OF PSNCB. PMID- 27254235 TI - Vibration for Pain Reduction in a Plastic Surgery Clinic. AB - Patients can experience significant pain during routine procedures in the plastic surgery clinic. Methods for clinical pain reduction are often impractical, time consuming, or ineffective. Vibration is a safe, inexpensive, and highly applicable modality for pain reduction that can be readily utilized for a wide variety of procedures. This study evaluated the use of vibration as a viable pain reduction strategy in the clinical plastic surgery setting. Patients requiring at least 2 consecutive procedures that are considered painful were enrolled in the study. These included injections, staple removal, and suture removal. In the same patient, one half of the procedures were performed without vibration and the other half with vibration. After completing the procedures, the patients rated their pain with vibration and without vibration. The patient and the researcher also described the experience with a short questionnaire. Twenty-eight patients were enrolled in the study. Patients reported significantly less pain on the Numeric Rating Scale pain scale when vibration was used compared with the control group (p < .001). The average pain score was 3.46 without vibration and 1.93 with vibration, and vibration with injections resulted in the greatest improvement. Eighty-six percent of the patients claimed that vibration significantly reduced their pain. Vibration is an effective method of pain reduction. It significantly reduces the pain experienced by patients during minor office procedures. Given its practicality and ease of use, it is a welcome tool in the plastic surgery clinic. PMID- 27254236 TI - An Overview of Fat Grafting. AB - The use of autologous fat grafting for a wide variety of clinical applications has increased dramatically over the past few decades. The article provides an overview of the technique, a historic background, and briefly explores some of the current ways in which fat grafting is being used in plastic surgery. PMID- 27254237 TI - Can Probiotics Improve Your Surgical Outcomes? AB - Despite ongoing advances in medical technology, postoperative infections and infectious complications continue to be a significant cause of morbidity and mortality. Surgical trauma and prophylactic antibiotics disrupt the balance of the intestinal microbiota and barrier function of the gut, potentiating an enhanced inflammatory response and further immune system depression. With the increasing costs of health care and emergence of multidrug-resistant bacteria, alternative approaches must be explored. Many clinical studies have demonstrated that the use of probiotics, prebiotics, or a combination of both (synbiotics) as a part of innovative strategies can improve outcomes of elective abdominal and gastrointestinal surgical procedures. It has been demonstrated that probiotics play a role in gut barrier improvement and immunomodulation. However, it is evident that additional research is needed including larger, multicenter, randomized controlled trials to validate the safety and efficacy of their use in surgical patients. The purpose of this article is to discuss background of probiotic use in abdominal/gastrointestinal surgery, risk and benefits, clinical relevance for health care providers, and further implications for research. PMID- 27254238 TI - Promoting Health Literacy in the Nonsurgical Cosmetic Patient. AB - Significant numbers of adults, when presented with basic health care information, have been shown to struggle with their abilities to comprehend and integrate materials presented to them. This lack of perception underscores the essence of health literacy. Even though health literacy is a newer concept, its impact is gathering momentum, as politicians, health care providers, researchers, and the media become more aware of the extent this disparity is seen within the health care system and how it affects patient care. This article explores how nursing philosophy and knowledge development have the capacity to provide a solid infrastructure that may promote increased health literacy among patients within the nonsurgical cosmetic arena. PMID- 27254239 TI - An Inquiry Into the Role of the Aesthetic Nurse: "Should Nurses Sell?". AB - I am a registered nurse, working for more than a decade. In the last few years, I decided to pursue my passion in the field of medical aesthetics. I invested in learning new skills through training and certification programs and was excited to attain employment in my chosen field. Yet, despite my qualifications, many employers were measuring my competency as an aesthetic nurse on the number of neuromodulators and dermal fillers I was able to inject or, to put it bluntly, able to sell. Many asked me to role-play exactly how and what I would say to "close the sale." These experiences caused me to reflect "Should nurses sell?" and "Is it ethical for nurses to sell?" In this article, I set out to explore these dilemmas and their implications on the role of the aesthetic nurse, using diverse perspectives in the current literature. PMID- 27254240 TI - Congenital Hand Differences. AB - Congenital hand differences are frequently encountered by pediatric plastic surgeons. These anomalies may cause significant emotional and functional challenges for children. Pediatric plastic surgery nurses should have a basic understanding of common congenital hand differences and related treatment options to facilitate patient education and postoperative care. This article discusses clinical findings and management of 4 of the most common hand anomalies: syndactyly, polydactyly, thumb hypoplasia, and cleft hand. The goals of surgical treatment are to maximize hand function and aesthetics with minimal adverse outcomes. PMID- 27254241 TI - Breast Rash After Breast Reduction: A Case Study. AB - Breast reduction surgery is one of the most common procedures done by plastic surgeons. Although not detrimental to the final outcome, allergic reaction can negatively impact the postoperative course. This case presentation paints the classic picture of allergic reaction after breast surgery, likely due to skin glue. The typical signs of intense pruritus and erythematous rash surrounding incisions bilaterally are present. The patient was treated with our institutional protocol with good results. Our protocol is presented and further questions posed. PMID- 27254242 TI - Vibration for Pain Reduction in a Plastic Surgery Clinic. PMID- 27254243 TI - Congenital Hand Differences. PMID- 27254244 TI - Kinetic Growth of Ultralong Metastable Zincblende MnSe Nanowires Catalyzed by a Fast Ionic Conductor via a Solution-Solid-Solid Mechanism. AB - The metastable semiconductor phase allows for the exploration of unusual properties and functionalities of abnormal structures, although it is often difficult to prevent thermodynamic transformations to lower energy structures from higher, unfavored energy states. Here, we show for the first time the preparation of high-quality ultralong metastable zincblende (ZB)-MnSe nanowires with a four-coordinate structure via solution-solid-solid (SSS) growth in a mild solution-phase synthetic environment (120-220 degrees C) in the presence of a trace amount of Ag(I). The metastable ZB-MnSe nanowires are stabilized kinetically due to the catalysis of early formed body-centered cubic (bcc) fast ionic (superionic) Ag2Se nanocrystals from the Ag(I) source, and the ZB-MnSe nanowires grow epitaxially along the ?110? axis rather than the ?111? axis, as commonly observed for typical four-coordinate Grimm-Sommerfeld bonding solids. Our method provides a new route for the growth of metastable nanostructures. PMID- 27254245 TI - Synthesis and characterization of an A2BC type phthalocyanine and its visible light-responsive photocatalytic H2 production performance on graphitic carbon nitride. AB - A highly asymmetric A2BC type zinc phthalocyanine (Zn-di-PcNcTh) has been designed and synthesized. The Zn-di-PcNcTh used a pi electron rich thiophene ring in place of the benzenoid rings of phthalocyanine which acted as an electron donor, diphenylphenoxy substituents to retard aggregation and a carboxyl naphthalene unit as an electron acceptor. The asymmetric phthalocyanine shows a strongly split Q-band and wide spectral absorption in the visible/near-IR light region, which can extend the spectral response region of graphitic carbon nitride (g-C3N4) from ~450 nm to more than 800 nm. By using it as a sensitizer of 1.0 wt% Pt-loaded graphitic carbon nitride (g-C3N4), the experimental results indicate that Zn-di-PcNcTh-Pt/g-C3N4 shows a H2 production efficiency of 249 MUmol h(-1) with an impressive turnover number (TON) of 9960.8 h(-1) under visible light (lambda>= 420 nm) irradiation, much higher than that of pristine Pt/g-C3N4. Owing to the introduction of a highly bathochromic shift of 3,4-dicyanothiophene and the valuable "push-pull" effect from the thiophene (electron donor) to the carboxyl-naphthalene (electron acceptor) unit, Zn-di-PcNcTh/g-C3N4 gives an extremely high apparent quantum yield (AQY) of 2.44%, 3.05%, and 1.53% under 700, 730, and 800 nm monochromatic light irradiation, respectively, under optimized photocatalytic conditions. PMID- 27254246 TI - Corrigendum: Intrinsic challenges in ancient microbiome reconstruction using 16S rRNA gene amplification. PMID- 27254247 TI - Reactive oxygen species acts as executor in radiation enhancement and autophagy inducing by AgNPs. AB - Malignant glioma is one of the most common intracranial tumor with a dismal prognosis. The radiosensitizing effect of silver nanoparticles (AgNPs) on glioma both in vitro and in vivo were demonstrated in the previous studies of our group. However, the underlying mechanism is still unclear. In this present study, the use of antioxidants is employed for the regulating of reactive oxygen species (ROS) in U251 cells treated with various agents, and the results shows that ROS played an essential role in the autophagy inducing and radiosensitization effect of AgNPs. Moreover, the inhibition of protective autophagy with 3-MA is another way to increase ROS, resulting in the increasing of cell death and apoptosis. Taken together, understanding the relationship between the elevated ROS and autophagy and the effect of ROS should be useful to the clinical applications of AgNPs. These findings could potentially be exploited for new therapeutic strategies in glioma radiotherapy. PMID- 27254248 TI - Interim Guidance for Interpretation of Zika Virus Antibody Test Results. AB - Zika virus is a single-stranded RNA virus in the genus Flavivirus and is closely related to dengue, West Nile, Japanese encephalitis, and yellow fever viruses (1,2). Among flaviviruses, Zika and dengue virus share similar symptoms of infection, transmission cycles, and geographic distribution. Diagnostic testing for Zika virus infection can be accomplished using both molecular and serologic methods. For persons with suspected Zika virus disease, a positive real-time reverse transcription-polymerase chain reaction (rRT-PCR) result confirms Zika virus infection, but a negative rRT-PCR result does not exclude infection (3-7). In these cases, immunoglobulin (Ig) M and neutralizing antibody testing can identify additional recent Zika virus infections (6,7). However, Zika virus antibody test results can be difficult to interpret because of cross-reactivity with other flaviviruses, which can preclude identification of the specific infecting virus, especially when the person previously was infected with or vaccinated against a related flavivirus (8). This is important because the results of Zika and dengue virus testing will guide clinical management. Pregnant women with laboratory evidence of Zika virus infection should be evaluated and managed for possible adverse pregnancy outcomes and be reported to the U.S. Zika Pregnancy Registry or the Puerto Rico Zika Active Pregnancy Surveillance System for clinical follow-up (9,10). All patients with clinically suspected dengue should have proper management to reduce the risk for hemorrhage and shock (11). If serologic testing indicates recent flavivirus infection that could be caused by either Zika or dengue virus, patients should be clinically managed for both infections because they might have been infected with either virus. PMID- 27254249 TI - Uptake of inorganic and organic nutrient species during cultivation of a Chlorella isolate in anaerobically digested dairy waste. AB - A natural assemblage of microalgae from a facultative lagoon system treating municipal wastewater was enriched for growth in the effluents of an anaerobic digester processing dairy waste. A green microalga with close resemblance to Chlorella sp. was found to be dominant after multiple cycles of sub-culturing. Subsequently, the strain (designated as LLAI) was isolated and cultivated in 20* diluted digester effluents under various incident light intensities (255-1,100 umoles m-2 s-1 ) to systematically assess growth and nutrient utilization. Our results showed that LLAI production increased with increasing incident light and a maximum productivity of 0.34 g L-1 d-1 was attained when the incident irradiance was 1,100 umoles m-2 s-1 . Lack of growth in the absence of light indicated that the cultures did not grow heterotrophically on the organic compounds present in the medium. However, the cultures were able to uptake organic N and P under phototrophic conditions and our calculations suggest that the carbon associated with these organic nutrients contributed significantly to the production of biomass. Overall, under high light conditions, LLAI cultures utilized half of the soluble organic nitrogen and >90% of the ammonium, orthophosphate, and dissolved organic phosphorus present in the diluted waste. Strain LLAI was also found to accumulate triacylglycerides (TAG) even before the onset of nutrient limitation and a lipid productivity of 37 mg-TAG L-1 d-1 was measured in cultures incubated at an incident irradiance of 1,100 umoles m-2 s-1 . The results of this study suggest that microalgae isolates from natural environments are well-suited for nutrient remediation and biomass production from wastewater containing diverse inorganic and organic nutrient species. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1336-1342, 2016. PMID- 27254250 TI - Boron Nitride Nanosheet-Veiled Gold Nanoparticles for Surface-Enhanced Raman Scattering. AB - Atomically thin boron nitride (BN) nanosheets have many properties desirable for surface-enhanced Raman spectroscopy (SERS). BN nanosheets have a strong surface adsorption capability toward airborne hydrocarbon and aromatic molecules. For maximized adsorption area and hence SERS sensitivity, atomically thin BN nanosheet-covered gold nanoparticles have been prepared for the first time. When placed on top of metal nanoparticles, atomically thin BN nanosheets closely follow their contours so that the plasmonic hot spots are retained. Electrically insulating BN nanosheets also act as a barrier layer to eliminate metal-induced disturbances in SERS. Moreover, the SERS substrates veiled by BN nanosheets show an outstanding reusability in the long term. As a result, the sensitivity, reproducibility, and reusability of SERS substrates can be greatly improved. We also demonstrate that large BN nanosheets produced by chemical vapor deposition can be used to scale up the proposed SERS substrate for practical applications. PMID- 27254251 TI - Genomic determinants of cancer immunotherapy. AB - Cancer immunotherapies - including therapeutic vaccines, adoptive cell transfer, oncolytic viruses, and immune checkpoint blockade - yield durable responses in many cancer types, but understanding of predictors of response is incomplete. Genomic characterization of human cancers has already contributed to the success of targeted therapies; in cancer immunotherapy, identification of tumor-specific antigens through whole-exome sequencing may be key to designing individualized, highly immunogenic therapeutic vaccines. Additionally, pre-treatment tumor mutational and gene expression signatures can predict which patients are most likely to benefit from cancer immunotherapy. Continued work in harnessing genomic, transcriptomic, and immunological data from clinical cohorts of immunotherapy-treated patients will bring the promises of precision medicine to immuno-oncology. PMID- 27254252 TI - Influence of the interface on the optical activity of confined glucose films. AB - We report on the time evolution of the optical activity of a thinning liquid film containing glucose, and confined between two glass slides. This dynamics strongly depends on the presence of surfactant molecules. With sodium dodecyl sulfate (SDS), we evidence favorable interactions of sugar molecules with the sulfate group. As previously observed for a freely suspended soap film in the air (see Emile et al., 2013), this corresponds to an anchoring of glucose molecules at the interface. For glucose alone, we also highlight a molecular rearrangement that is not instantaneous and occurs after several minutes. This interfacial organization leads to an unusual giant optical activity that is different with or without SDS. Molecular simulations confirm the anchoring of the glucose molecules at the glass/liquid interface, and show a different molecular orientation in each case. PMID- 27254253 TI - Influence of the mutable kinetic parameters on the adhesion and debonding of thin viscoelastic films. AB - Detachment of a surface from a viscoelastic layer, such as a film of glue, engenders bridges between the surfaces until separation. Such surface instabilities arising during contact and detachment of viscoelastic films with rigid contactors have been theoretically explored by linear stability analysis and nonlinear simulations. The contact instabilities of viscoelastic materials are found to manifest in either a 'critical' or a 'dominant' mode in which the former is preferred when the contactor is slowly brought near the film while the latter manifests when the film is 'hard-pressed' against it. The nonlinear analysis considers the movement of contactor during adhesion-debonding cycle, which uncovers that the kinetic parameters can overshadow the thermodynamically predicted area of contact, average force for pull-off, energy of contactor-film separation, and pathways of debonding. Three distinct pathways of debonding - peeling, catastrophic column collapse, and column coalescence, are found to manifest with the variation in the ratio of the elastic to viscous compliances of the viscoelastic film. The study also reveals that in the dominant mode of instability, a smaller length scale with a larger area contact between the contactor and film can develop patterns having aspect ratio ~10 times larger than the same obtained from elastic film. PMID- 27254254 TI - Protein immobilization and fluorescence quenching on polydopamine thin films. AB - Mussel inspired polydopamine (PDA) film has attracted great interest as a versatile functional coating for biomolecule immobilization in various bio related devices. However, the details regarding the interaction between a protein and PDA film remain unclear. Particularly, there is very limited knowledge regarding the protein immobilization on PDA film, even though it is of essential importance in various fields. The situation is even more complicated if considering the fact that quite a number of approaches (e.g., different oxidizing reagent, buffer pH, grown time, grown media, etc.) have been developed to grow PDA films. In this work, protein attachment on PDA film was systematically investigated by using the real-time and label-free surface plasmon resonance (SPR) technique. The kinetics of protein-PDA interaction was explored and the influence of buffer pH and deposition media on the protein attachment was studied. Fluorescent protein microarray was further printed on PDA-coated glass slides for quantitative investigations and together with SPR data, the interesting fluorescence quenching phenomenon of PDA film was revealed. This work may deepen our understanding on the PDA-protein interaction and offer a valuable guide for efficient protein attachment on PDA film in various bio-related applications. PMID- 27254255 TI - Hydrogenation of nitroarenes into aromatic amines over Ag@BCN colloidal catalysts. AB - The present work reports that two-dimension layered ternary boron carbon nitrogen nanosheets can serve as good carriers to support and disperse noble metal nanoparticles. The Ag@BCN colloids have thus been prepared by attaching Ag nanoparticles on the surfaces of BCN nanosheets. The detailed structures of the Ag@BCN samples were investigated by X-ray diffraction, transmission electron microscopy, atomic force microscope, infrared, and X-ray photoelectron spectroscopy. It is found that the surface NH groups of BCN nanosheets are beneficial for the attachment of Ag nanopaprticles. Compared with the conventional organic capping compounds, the two dimensional planar BCN nanosheets endow the attached nanoparticle with the high active surfaces. Moreover, the hydrogenation of nitroarenes into the corresponding aromatic amines can be highly achieved over Ag@BCN colloids by NaBH4. In particular, the apparent activation energy of the conversion reaction of p-nitroaniline to p-phenylenediamine was found to be 76.0kJ/mol over the Ag@BCN colloids with 3wt% Ag content. Our results may provide a new approach for the design noble metal based composites and find the practical application for the hydrogenation of nitroarenes. PMID- 27254256 TI - The effects of pore structure on the behavior of water in lignite coal and activated carbon. AB - The effects of physical structure (pore structure) on behavior of water in lignite coal and activated carbon (AC) samples were investigated by using Differential Scanning Calorimetry (DSC) and low-temperature X-ray diffraction (XRD) techniques. AC samples with different pore structures were prepared at 800 degrees C in steam and the results were compared with that of parent lignite coal. The DSC results confirmed the presence of two types of freezable water that freeze at -8 degrees C (free water) and -42 degrees C (freezable bound water). A shift in peak position of free water (FW) towards lower temperature was observed in AC samples compared to the lignite coal with decreasing water loading. The amount of free water (FW) increased with increasing gasification conversion. The amounts of free and freezable bound water (FBW) in AC samples were calculated and correlated to pore volume and average pore size. The amount of FW in AC samples is well correlated to the pore volume and average pore size of the samples, while an opposite trend was observed for FBW. The low-temperature XRD analysis confirmed the existence of non-freezable water (NFW) in coal and AC with the boundary between the freezable and non-freezable water (NFW) determined. PMID- 27254257 TI - Monitoring the role of Mn and Fe in the As-removal efficiency of tetravalent manganese feroxyhyte nanoparticles from drinking water: An X-ray absorption spectroscopy study. AB - The implementation of amorphous tetravalent manganese feroxyhyte (TMFx) nanoparticles, prepared via co-precipitation synthesis, as an efficient As(V) removal material is investigated using X-ray absorption fine structure (XAFS) spectroscopy at the Fe-, Mn- and As-K-edges. The optimum synthesis conditions and chemical composition of the TMFx adsorbent were determined by the degree of polymerization in the adsorbents' microstructure. Under synthesis into mildly acidic conditions, the change in the polymerization of the metal-oxyhydroxyl chains (metal=Fe, Mn) provides more adsorption sites at edges and corner sites in the bonding environment of Fe and Mn, respectively, thereby enhancing As uptake. After exposure to As-polluted water, similar microstructural changes related to As-bidentate and monodentate geometries are generated: As(V) preferentially occupies the high energy adsorption sites ((2)C complexes) available in the Mn oxyhydroxyl groups and the low energy edge sites offered by Fe ((2)E complexes). It is revealed that optimum arsenic-removal by TMFx occurs into mildly acidic synthesis pH and for iron to manganese molar ratio equal to 3. PMID- 27254259 TI - Letter to the editor: Specificity of Zika virus ELISA: interference with malaria. PMID- 27254258 TI - Buspirone reduces sexual risk-taking intent but not cocaine self-administration. AB - Impulsive sexual decision-making may underlie sexual risk-taking behavior that contributes to the disproportionately high prevalence of HIV infection among cocaine users. Delay-discounting procedures measure impulsive decision-making and may provide insight into the underlying mechanisms of sexual risk-taking behavior. The anxiolytic drug buspirone reduces delay discounting in rats and blunts the reinforcing effects of cocaine in some preclinical studies suggesting that it might have utility in the treatment of cocaine-use disorders. This study determined whether buspirone mitigates impulsive risky sexual decision-making in cocaine users on a sexual delay-discounting procedure. The effects of buspirone maintenance on the abuse-related and physiological effects of cocaine were also tested. Nine (N = 9) current cocaine users completed a repeated-measures, inpatient protocol in which sexual delay discounting was assessed after 3 days of maintenance on placebo and buspirone (30 mg/day) in counterbalanced order. The reinforcing, subject-rated, and physiological effects of placebo and intranasal cocaine (15 and 45 mg) were also assessed during buspirone and placebo maintenance. Buspirone increased the likelihood of condom use for hypothetical sexual partners that were categorized as most likely to have a sexually transmitted infection and least sexually desirable. Cocaine functioned as a reinforcer and increased positive subjective effects ratings, but buspirone maintenance did not impact these effects of cocaine. Buspirone was also safe and tolerable when combined with cocaine and may have blunted some its cardiovascular effects. The results from the sexual delay-discounting procedure indicate that buspirone may reduce preference for riskier sex in cocaine users. (PsycINFO Database Record PMID- 27254260 TI - Hip Strength in Patients with Quadriceps Strength Deficits after ACL Reconstruction. AB - PURPOSE: Quadriceps strength deficits persist for years after anterior cruciate ligament (ACL) reconstruction, and patients with these deficits often shift torque demands away from the knee extensors to the hip during functional tasks. However, it is not clear how quadriceps strength deficits may affect hip strength. Therefore, the purpose of this study was to investigate differences in lower extremity strength in individuals with ACL reconstruction with differing levels of quadriceps strength asymmetry. METHODS: Isometric strength was recorded bilaterally in 135 participants (73 control and 62 with unilateral ACL reconstruction, time from surgery = 30.9 +/- 17.6 months) from the knee extensors and flexors, hip extensors and abductors, and hip internal and external rotator muscle groups. Symmetry indices (limb symmetry index (LSI)) were created based on quadriceps strength, and subjects with ACL reconstruction were subdivided (high quadriceps (LSI >= 90%), n = 37; low quadriceps (LSI < 85%), n = 18). Individual group (control vs high quadriceps vs low quadriceps) by limb (reconstructed/nondominant vs healthy/dominant) repeated-measures ANOVA was used to compare strength (%BW) for each of the six joint motions of interest (knee extensors/flexors, hip abductors/extensors/external, and internal rotators) while controlling for time from surgery. RESULTS: An interaction was observed for quadriceps strength (P < 0.001), and the reconstructed limb in the low quadriceps group was weaker than all other limbs. A main effect for group was observed with the low quadriceps group having greater hip extension (P = 0.007) strength in both limbs compared with the other groups. Knee flexion strength was weaker in the reconstructed limb of the high quadriceps group (P = 0.047) compared with all other groups and limbs. CONCLUSIONS: Individuals with ACL reconstruction and involved limb quadriceps weakness have greater hip extension strength in both limbs compared with patients with bilateral strength symmetry and controls. PMID- 27254261 TI - Overuse Injuries of the Pediatric and Adolescent Throwing Athlete. AB - In the hypercompetitive environment of year round youth baseball, arm pain is commonplace. Although much research has been done about injuries in the overhead throwing athlete, the emphasis has been on the more elite levels, where athletes have reached full development. The anatomy of the skeletally immature athlete, including open physeal plates and increased tissue laxity, raises unique issues in the presentation and treatment of repetitive throwing injuries of the elbow and shoulder. With a focus on "little leaguers," this discussion evaluates five of the most common elbow and shoulder injuries-Little Leaguer's elbow, ulnar collateral ligament sprain or tear, osteochondritis dissecans/Panner's disease, Little Leaguer's shoulder, and multidirectional instability. In the developmentally distinct pediatric athlete, pathogenesis, diagnosis, and treatment may differ from that established for adults. Offering early diagnosis and treatment appropriate to a child's level of development will enable youth to not only continue to play sports but to also maintain full functionality as active adults. PMID- 27254262 TI - Sensorimotor Learning in a Computerized Athletic Training Battery. AB - Sensorimotor abilities are crucial for performance in athletic, military, and other occupational activities, and there is great interest in understanding learning in these skills. Here, behavioral performance was measured over three days as twenty-seven participants practiced multiple sessions on the Nike SPARQ Sensory Station (Nike, Inc., Beaverton, Oregon), a computerized visual and motor assessment battery. Wrist-worn actigraphy was recorded to monitor sleep-wake cycles. Significant learning was observed in tasks with high visuomotor control demands but not in tasks of visual sensitivity. Learning was primarily linear, with up to 60% improvement, but did not relate to sleep quality in this normal sleeping population. These results demonstrate differences in the rate and capacity for learning across perceptual and motor domains, indicating potential targets for sensorimotor training interventions. PMID- 27254264 TI - Alaska. PMID- 27254263 TI - Closing the Gap between Policy and Practice in Screening for Perinatal Depression: A Policy Analysis and Call for Action. AB - Although perinatal depression (PND) is one of the most common maternal morbidities, it is frequently undetected. Screening for early detection and intervention has the potential to prevent depressive symptoms from worsening. In the United States, five states have enacted legislation in relation to screening for PND, but a gap remains between policy and practice in providing continuum of care for mothers who may be suffering from depressive symptoms. From the perspective of policy formation, the reasons for this gap include a discrepancy between policy and practice goals, lack of regulations on capability building among perinatal care providers, and few pathways for establishing collaborations between medical providers and mental health professionals. The authors recommend involving social workers in the process to promote a better continuum of care after screening through comprehensive policy that explicitly states goals to effectively screen women in the perinatal period. PMID- 27254266 TI - Pituitary diseases and sleep disorders. AB - PURPOSE OF REVIEW: Patients with pituitary diseases have decreased quality of life. Sleep disorders are prevalent among patients with pituitary diseases and contribute to decreased quality of life. RECENT FINDINGS: Patients previously treated for compression of the optic chiasm by surgery, and in some cases postoperative radiotherapy, suffer from sleep disorders. These are characterized by decreased sleep quality, delayed onset of sleep, and daytime sleepiness. Circumstantial evidence suggests that this may be caused by hypothalamic dysfunction. A challenging speculation is that previous compression of the optic chiasm compromised the function of the retinohypothalamic tract. Through this tract the eyes convey information on day-night cycles to the hypothalamic nuclei. Patients with acromegaly, even despite biochemical control, suffer frequently from obstructive sleep apnea. Patients with Cushing's disease suffer from fragmented sleep, sleep apnea, and snoring. Prolactinomas do not seem to affect sleep characteristics. The association between appropriately substituted pituitary insufficiency and sleep disorders is less clear. The effects of recombinant human growth hormone on sleep characteristics in adults are inconsistent. SUMMARY: Pituitary disorders are associated with different sleep disorders. Different studies point to irreversible changes in sleep-wake rhythmicity in patients treated previously for pituitary tumors with chiasm compression. VIDEO ABSTRACT. PMID- 27254265 TI - Heme Mobilization in Animals: A Metallolipid's Journey. AB - Heme is universally recognized as an essential and ubiquitous prosthetic group that enables proteins to carry out a diverse array of functions. All heme dependent processes, from protein hemylation to heme signaling, require the dynamic and rapid mobilization of heme to hemoproteins present in virtually every subcellular compartment. The cytotoxicity and hydrophobicity of heme necessitates that heme mobilization is carefully controlled at the cellular and systemic level. However, the molecules and mechanisms that mediate heme homeostasis are poorly understood. In this Account, we provide a heuristic paradigm with which to conceptualize heme trafficking and highlight the most recent developments in the mechanisms underlying heme trafficking. As an iron-containing tetrapyrrole, heme exhibits properties of both transition metals and lipids. Accordingly, we propose its transport and trafficking will reflect principles gleaned from the trafficking of both metals and lipids. Using this conceptual framework, we follow the flow of heme from the final step of heme synthesis in the mitochondria to hemoproteins present in various subcellular organelles. Further, given that many cells and animals that cannot make heme can assimilate it intact from nutritional sources, we propose that intercellular heme trafficking pathways must exist. This necessitates that heme be able to be imported and exported from cells, escorted between cells and organs, and regulated at the organismal level via a coordinated systemic process. In this Account, we highlight recently discovered heme transport and trafficking factors and provide the biochemical foundation for the cell and systems biology of heme. Altogether, we seek to reconceptualize heme from an exchange inert cofactor buried in hemoprotein active sites to an exchange labile and mobile metallonutrient. PMID- 27254267 TI - Type B insulin resistance syndrome. AB - PURPOSE OF REVIEW: To review the epidemiology, pathophysiology, clinical features, and management of type B insulin resistance syndrome. RECENT FINDINGS: Type B insulin resistance syndrome is a rare disorder caused by autoantibodies to the insulin receptor. This disorder is most frequently reported in middle-aged black women and is invariably associated with other autoimmune diseases. Typically, refractory transient hyperglycemia and extreme insulin resistance are the cardinal features, but hypoglycemia may also occur. Traditionally, the high reported mortality rate was typically attributed to the hypoglycemia. There is no well standardized treatment regimen. However, recent therapeutic advances with combination immunomodulatory therapy have led to significant reported improvements in hypoglycemia-associated mortality and durability of remission. SUMMARY: We review the literature on the pathophysiology and clinical features of type B insulin resistance syndrome and highlight the complexities and recent advances in the management of this disorder. PMID- 27254268 TI - Nucleic acid biomarkers of beta cell stress and death in type 1 diabetes. AB - PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances in the development of nucleic acid-based biomarkers of type 1 diabetes (T1D). RECENT FINDINGS: Recent rodent and human studies have identified new roles for stress pathways intrinsic to the beta cell during the development of T1D. As such, methods to identify an authentic nucleic acid signature of beta cell stress and/or death may improve our ability to predict T1D at earlier timepoints, allowing for optimal timing of immunomodulatory interventions. To this end, both targeted and unbiased approaches have begun to identify changes in microRNA expression patterns in T1D. Moreover, a number of groups have developed distinct assays that quantitatively detect circulating unmethylated insulin DNA, which is thought to primarily emanate from dying beta cells. SUMMARY: Here we highlight unique blood and urine microRNA signatures identified in T1D cohorts, compare differences between first, second, and third-generation assays that detect circulating unmethylated insulin DNA, and review recent technological advances that have the capacity to improve T1D biomarker development. PMID- 27254269 TI - Molecular markers in pituitary tumors. AB - PURPOSE OF REVIEW: This review summarizes our current understanding of the mechanisms and factors involved in pituitary tumorigenesis. It provides a comprehensive review on the role of genetic mutations, epigenetics, oncogenes, tumor suppressor genes, cell cycle deregulation, and highlights recent findings of altered micro-RNA and long noncoding RNA expression in pituitary tumors. RECENT FINDINGS: This article provides a concise summary of our knowledge regarding oncogenes, tumor suppressor genes, and cell cycle deregulation in pituitary tumors. Additionally, it highlights new findings in epigenetics and altered micro-RNA and long noncoding RNA expression in pituitary tumors. SUMMARY: Improved understanding of the mechanism(s) and candidates implicated in pituitary tumorigenesis may result in the identification of new therapeutic targets in pituitary tumors. PMID- 27254270 TI - Management of candidemia in patients with Clostridium difficile infection. AB - INTRODUCTION: Patients with C. difficile infection (CDI) experience intestinal microflora changes that can promote the overgrowth and subsequent translocation of gut resident pathogens into the blood. Consistently, CDI due to PCR-ribotype 027 strain, severe or relapsing CDI, and treatment with high-dosage vancomycin are independent risk factors for candidemia. AREAS COVERED: We review the role played by the gut microbiota during CDI and its treatment, as well as the clinical profile of CDI patients who are at risk of developing candidemia. Also, we discuss the management of these patients by focusing on pre-emptive strategies aimed at reducing the risk of candidemia, and on innovative anti-C. difficile therapies that may mitigate CDI-related effects such as the altered gut microbiota composition and prolonged intestinal mucosa damage. Expert commentary: A closer clinical and diagnostic monitoring of patients with CDI should help to limit the CDI-associated long-term consequences, including Candida infections, which worsen the outcome of hospitalized patients. PMID- 27254271 TI - Synthesis of 1,2,3,4-tetrasubstituted naphthalenes through a cascade reaction triggered by silyl acetal activation. AB - 1,2,3,4-Tetrasubstituted naphthalenes bearing four different substituents were synthesized in a regioselective manner through a fluoride-induced cascade reaction of lactol silyl ethers, which could be easily prepared from 4 alkynylisocoumarins and ketene silyl acetal. PMID- 27254272 TI - Interventions for cancer-related fatigue: a scoping review. AB - Cancer-related fatigue (CRF) is common and can be distressing for some survivors. There is increasing interest in measuring levels of CRF, highlighting its impact on quality of life. This review describes the nature and scope of evidence relating to interventions for CRF. Scoping review methodology was used to identify studies, extract data, collate and summarise results. Data were collated according to cancer tumour streams, stage of illness and the types of trial interventions. A total of 447 trials and 37 systematic reviews met the inclusion criteria. Nine papers reported longitudinal results. Populations studied were predominantly of mixed cancer diagnoses and breast cancer. The most frequent interventions were exercise, pharmacological, psycho-education and mind-body interventions. Fatigue was identified as a primary outcome measure (OM) in 58% of studies, with 58 different fatigue measures reported. Emerging evidence exists for the effectiveness of fatigue interventions for some cancer types. More research on interventions with participants with the same cancer type and illness phase is needed. Measurement of severity and impact of CRF using fewer, robust OMs will permit comparisons across studies. PMID- 27254273 TI - Bridging the gap between regulatory acceptance and industry use of non-animal methods. AB - Collaboration between industry and regulators resulted in the development of a decision tree approach using in vitro or ex vivo assays to replace animal tests when determining the eye irritation potential of antimicrobial cleaning products (AMCPs) under the United States Environmental Protection Agency (EPA) Office of Pesticide Programs' hazard classification and labeling system. A policy document issued by the EPA in 2013 and updated in 2015 describes the alternate testing framework that industry could apply to new registrations of AMCPs and, on a case by-case basis, to conventional pesticide products. Despite the collaborative effort, the availability of relevant non-animal methods, and the EPA's change in policy, only a limited number of AMCPs have been registered using the framework. Companies continue to conduct animal tests when registering AMCPs due to various challenges surrounding adoption of the new testing framework; however, recent discussions between industry, regulators, and other interested parties have identified ways these challenges may be overcome. In this article we explore how use of the alternate framework could be expanded through efforts such as increasing international harmonization, more proactively publicizing the framework, and enhancing the training of regulatory reviewers. Not only can these strategies help to increase use of the EPA alternate eye irritation framework, they can also be applied to facilitate the uptake of other alternative approaches to animal testing in the future. PMID- 27254274 TI - Deep brain stimulation for the treatment of hyperkinetic movement disorders. AB - INTRODUCTION: Deep brain stimulation effectiveness is well recognized for different movement disorders including Parkinson's disease, dystonia and essential tremor, however several other diseases in this field may benefit from the technique although experience is sparse and evidences of benefit and risks are not established. AREAS COVERED: In this review, we explored available evidence for effectiveness and safety of DBS in selected hyperkinetic movement disorders, including tardive dyskinesia, Huntington's disease, neuroacanthocytosis, myoclonus-dystonia, Tourette syndrome, orthostatic and Holmes' tremor. Expert commentary: The data referenced and discussed showed potential effectiveness for DBS in these disabling and refractory diseases. On the other hand, these disorders are quite complex and multifaceted, often composed of different movement disorders, as well as other motor and non-motor symptoms. Therefore, the possible contribution of DBS in improving patients' quality of life should be weighted in a strictly individual basis, keeping in mind the progressive nature of most of these disorders, as well as risk/benefit ratio. PMID- 27254275 TI - Expert opinion: the therapeutic challenges faced by statin intolerance. AB - INTRODUCTION: Statin intolerance is largely defined by muscle related symptoms, leading to intolerability and cessation. The nocebo effect coupled with the challenges of diagnosing statin myopathy undermines drug adherence that is critical for achieving the benefits of lipid-lowering and cardiovascular risk reduction. A temporal relationship should be made between the initiation of therapy and development of symptoms to aid in diagnosis. The mainstay of treatment is statin cessation or statin dose reduction and evaluation of alternative causes for muscle related symptoms. Most symptoms usually resolve within 2 weeks of discontinuing therapy. The patient can be re-challenged with the same statin at a lower dose or an alternative statin. Non-statin lipid lowering therapies offer an alternative to patients who cannot tolerate statins. AREAS COVERED: We discuss current guideline-focused management of patients with statin intolerance. EXPERT OPINION: When initiating statin therapy, attention to risk factors for statin intolerance is strongly recommended. Most patients will tolerate some degree of statin therapy; thus statin re-challenge is advisable. If alternative dosing regimens are not tolerated, non-statin medications are acceptable alternatives. To limit errors in the diagnosis of statin intolerance, improvements in clinician-patient communication about the side effects and benefits of statins should be attempted. PMID- 27254276 TI - Loss of tyrosine phosphorylation at Y406 abrogates the tumor suppressor functions of the thyroid hormone receptor beta. AB - We have recently identified that phosphorylation at tyrosine (Y)406 is critical for the tumor suppressor functions of the thyroid hormone receptor beta1 (TRbeta) in a breast cancer line. However, still unclear is whether the critical tumor suppressor role of phosphorylated Y406 of TRbeta is limited to only breast cancer cells or could be extended to other cell types. In the present studies, we addressed this question by stably expressing TRbeta, a mutated TRbeta oncogene (PV), or a TRbeta mutated at Y406 (TRbetaY406F) in rat PCCL3 thyroid follicular cells and evaluated their tumor characteristics in athymic mice with elevated thyroid stimulating hormone. PCCL3 cells stably expressing PV (PCCL3-PV), TRbetaY406F (PCCL3-TRbetaY406F), or vector only (PCCL3-Neo) developed tumors with sizes in the rank order of TRbetaY406F>PV = Neo, whereas PCCL3 cells expressing TRbeta (PCCL3-TRbeta) barely developed tumors. As evidenced by markedly elevated Ki67, cyclin D1, and p-Rb protein abundance, proliferative activity was high in PV and TRbetaY406F tumors, but low in TRbeta tumors. These results indicate that TRbeta acted as a tumor suppressor in PCCL3 cells, whereas TRbetaY406F and PV had lost tumor suppressor activity. Interestingly, TRbetaY406F tumors had very low necrotic areas with decreased TNFalpha-NFkappaB signaling to lower apoptotic activity. In contrast, PV tumors had prominent large necrotic areas, with no apparent changes in TNFalpha-NFkappaB signaling, indicating distinct oncogenic activities of mutant PV and TRbetaY406F. Thus, the present studies uncovered a novel mechanism by which TRbeta could function as a tumor suppressor through modulation of the TNFalpha-NFkappaB signaling. (c) 2016 Wiley Periodicals, Inc. PMID- 27254277 TI - Correction: Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial. AB - [This corrects the article DOI: 10.1371/journal.pone.0137834.]. PMID- 27254278 TI - A Single-Cell Assay for Time Lapse Studies of Exosome Secretion and Cell Behaviors. AB - To understand the inhomogeneity of cells in biological systems, there is a growing demand on the capability of characterizing the properties of individual single cells. Since single-cell studies require continuous monitoring of the cell behaviors, an effective single-cell assay that can support time lapsed studies in a high throughput manner is desired. Most currently available single-cell technologies cannot provide proper environments to sustain cell growth and, proliferation of single cells and convenient, noninvasive tests of single-cell behaviors from molecular markers. Here, a highly versatile single-cell assay is presented that can accommodate different cellular types, enable easy and efficient single-cell loading and culturing, and be suitable for the study of effects of in vitro environmental factors in combination with drug screening. One salient feature of the assay is the noninvasive collection and surveying of single-cell secretions at different time points, producing unprecedented insight of single-cell behaviors based on the biomarker signals from individual cells under given perturbations. Above all, the acquired information is quantitative, for example, measured by the number of exosomes each single-cell secretes for a given time period. Therefore, our single-cell assay provides a convenient, low cost, and enabling tool for quantitative, time lapsed studies of single-cell properties. PMID- 27254279 TI - Perforation forces of the intact porcine anterior lens capsule. AB - During the first step of cataract surgery, the lens capsule is perforated and a circular hole is created with a sharp instrument, a procedure called capsulorhexis. To develop automated systems that can assist ophthalmologists during capsulorhexis, the forces required must be quantified. This study investigates perforation forces of the central anterior lens capsule in porcine eyes, which are used as a conservative model for the human eye. A micro mechanical characterisation method is presented that measures capsular bag perforation forces with a high precision positioning and high-resolution force sensing system. The force during perforation of the anterior lens capsule was measured with various sized needles and indentation speeds and is found to be 15 35mN. A bio-mechanical model is identified that describes an exponential correlation between indentation force and depth, indicating strain hardening behaviour of the porcine anterior lens capsule. PMID- 27254280 TI - Optimization of process parameters for drilled hole quality characteristics during cortical bone drilling using Taguchi method. AB - Orthopaedic surgery involves drilling of bones to get them fixed at their original position. The drilling process used in orthopaedic surgery is most likely to the mechanical drilling process and there is all likelihood that it may harm the already damaged bone, the surrounding bone tissue and nerves, and the peril is not limited at that. It is very much feared that the recovery of that part may be impeded so that it may not be able to sustain life long. To achieve sustainable orthopaedic surgery, a surgeon must try to control the drilling damage at the time of bone drilling. The area around the holes decides the life of bone joint and so, the contiguous area of drilled hole must be intact and retain its properties even after drilling. This study mainly focuses on optimization of drilling parameters like rotational speed, feed rate and the type of tool at three levels each used by Taguchi optimization for surface roughness and material removal rate. The confirmation experiments were also carried out and results found with the confidence interval. Scanning electrode microscopy (SEM) images assisted in getting the micro level information of bone damage. PMID- 27254281 TI - Acid-resistant calcium silicate-based composite implants with high-strength as load-bearing bone graft substitutes and fracture fixation devices. AB - To achieve the excellent mechanical properties of biodegradable materials used for cortical bone graft substitutes and fracture fixation devices remains a challenge. To this end, the biomimetic calcium silicate/gelatin/chitosan oligosaccharide composite implants were developed, with an aim of achieving high strength, controlled degradation, and superior osteogenic activity. The work focused on the effect of gelatin on mechanical properties of the composites under four different kinds of mechanical stresses including compression, tensile, bending, and impact. The evaluation of in vitro degradability and fatigue at two simulated body fluid (SBF) of pH 7.4 and 5.0 was also performed, in which the pH 5.0 condition simulated clinical conditions caused by bacterial induced local metabolic acidosis or tissue inflammation. In addition, human mesenchymal stem cells (hMSCs) were sued to examine osteogenic activity. Experimental results showed that the appropriate amount of gelatin positively contributed to failure enhancement in compressive and impact modes. The 10wt% gelatin-containing composite exhibits the maximum value of the compressive strength (166.1MPa), which is within the reported compressive strength for cortical bone. The stability of the bone implants was apparently affected by the in vitro fatigue, but not by the initial pH environments (7.4 or 5.0). The gelatin not only greatly enhanced the degradation of the composite when soaked in the dynamic SBF solution, but effectively promoted attachment, proliferation, differentiation, and formation of mineralization of hMSCs. The 10wt%-gelatin composite with high initial strength may be a potential implant candidate for cortical bone repair and fracture fixation applications. PMID- 27254282 TI - Optimization of Norbornadiene Compounds for Solar Thermal Storage by First Principles Calculations. AB - Molecular photoswitches capable of storing solar energy are interesting candidates for future renewable energy applications. Here, using quantum mechanical calculations, we carry out a systematic screening of crucial optical (solar spectrum match) and thermal (storage energy density) properties of 64 such compounds based on the norbornadiene-quadricyclane system. Whereas a substantial number of these molecules reach the theoretical maximum solar power conversion efficiency, this requires a strong red-shift of the absorption spectrum, which causes undesirable absorption by the photoisomer as well as reduced thermal stability. These compounds typically also have a large molecular mass, leading to low storage densities. By contrast, single-substituted systems achieve a good compromise between efficiency and storage density, while avoiding competing absorption by the photo-isomer. This establishes guiding principles for the future development of molecular solar thermal storage systems. PMID- 27254283 TI - Aprepitant, granisetron, and dexamethasone versus palonosetron and dexamethasone for prophylaxis of cisplatin-induced nausea and vomiting in patients with upper gastrointestinal cancer: a randomized crossover phase II trial (KDOG 1002). AB - We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting. PMID- 27254284 TI - Knockdown of GRP78 enhances cell death by cisplatin and radiotherapy in nasopharyngeal cells. AB - Radiotherapy and adjuvant cisplatin chemotherapy are the mainstream approaches in the treatment of nasopharyngeal carcinoma (NPC). These have been shown to effectively improve the outcome and reduce tumor recurrence. However, radiotherapy and chemotherapy resistance during the course of treatment has become more common recently, resulting in the failure of NPC therapy. Therefore, new therapeutic strategies or adjuvant drugs are urgently needed. The current study was designed to look for new treatment strategies or auxiliary drugs in the treatment of NPC. Two human NPC cell lines, HNE1 and HNE1/DDP, were used to examine the relationship between endoplasmic reticulum stress and cell resistance to ionizing radiation (IR) and cisplatin (DDP). Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Meanwhile, propidium iodide (PI) staining and PI/Annexin V staining were used to observe cell apoptosis. Finally, western blot was used to detect the endogenous expression of glucose-regulated protein 78 (GRP78) and other apoptosis-related proteins. GRP78 small interference RNA was transfected using Lipofectamine 2000. Compared with HNE1/DDP, IR and DDP increased the cell apoptosis and inhibited the cell proliferation of HNE1. Inhibition of GRP78 can reverse IR and DDP resistance in NPC cells by PI/Annexin V staining. Knockdown of GRP78 upregulates the expression of pro-apoptotic proteins and downregulates the expression of antiapoptotic proteins. These results indicate that HNE1 is more sensitive to DDP and IR than HNE1/DDP. Knockdown GRP78 can reverse IR and DDP resistance in NPC cells. Inhibition of GRP78 gives us a new target to overcome resistance to radiotherapy and chemotherapy of NPC cells. Thus, this study should be further explored in vivo and assessed for possible clinical applications. PMID- 27254285 TI - Cytosine arabinoside and daunorubicin induction therapy in a patient with acute myeloid leukemia on chronic hemodialysis. AB - The combination of daunorubicin and cytarabine is the cornerstone of induction therapy for acute myeloid leukemia (AML). Little data are available on the optimal chemotherapy regimen for patients with AML and advanced renal failure, with some authors recommending administration of reduced daunorubicin doses. We report the case of a 54-year-old AML patient on chronic hemodialysis who was treated with a modified induction regimen with reduced-dose daunorubin. Daunorubicin levels were measured during the treatment schedule. Although daunorubicin terminal t1/2 appears to be unaffected in hemodialysis patients, the estimated 0-23 h area under the curve was comparable with that of patients receiving full-dose daunorubicin. Therefore, dose adjustment in this patient group may be prudent. PMID- 27254286 TI - Liver stiffness-based score in hepatoma risk assessment for chronic hepatitis C patients after successful antiviral therapy. AB - BACKGROUND & AIMS: Patients with chronic hepatitis C (CHC) after successful antiviral therapy remain at risk of hepatocellular carcinoma (HCC). This study was to determine whether liver stiffness measurement (LSM) was useful in HCC risk assessment and to develop a risk-score system for clinical use. METHODS: This retrospective study enrolled patients with CHC achieving sustained virological response (SVR) after interferon-based therapy with LSM at/after SVR determination. The demographics, clinical characteristics and HCC development were obtained from medical chart reviews. The diagnosis of HCC was based on recommended criteria. RESULTS: A total of 376 (M/F: 185/191, mean age: 54.1 years) patients, including 278 with pretreatment liver biopsy specimens, with a median follow-up period of 7.6 years were enrolled. Twenty-one patients developed HCC. The 5- and 10-year cumulative HCC incidences were 1.4% and 7.8%, respectively. Multivariate analysis showed advanced fibrosis/cirrhosis, diabetes and LSM were associated with HCC developments with odds ratio (OR) of 12.38, 2.80 and 1.01, respectively. For LSM in HCC prediction, the performance and cut-off were 0.783 and 12 kilopascal (kPa), respectively. For 278 patients with pretreatment biopsy, a risk-score system (score 0-4) combining advanced fibrosis/cirrhosis, diabetes and LSM >12 kPa was developed. With the low-risk group as a reference, patients in intermediate- (OR: 12.57) and high-risk (OR: 197.33) groups carried higher risk of HCC development. CONCLUSIONS: For patients with CHC achieving SVR, liver stiffness value at/after SVR determination was associated with HCC development independently. Patients with pretreatment advanced fibrosis/cirrhosis, diabetes and LSM >12 kPa after SVR were at high risk of HCC development. PMID- 27254287 TI - Amino- and Sulfo-Bifunctionalized Metal-Organic Frameworks: One-Pot Tandem Catalysis and the Catalytic Sites. AB - New MIL-101 metal-organic frameworks (MOFs) dually functionalized with amino and sulfo groups were fabricated by postsynthetic modification and used to catalyze one-pot deacetalization-Knoevenagel condensation. We proved that the MOFs take the zwitterionic form, with the catalytic acid site being the ammonium group rather than the sulfo one. The acid and base concentrations in the materials are correlated, and the ratio can be readily tuned to achieve optimal catalytic performance. PMID- 27254288 TI - The Ankylosing Spondylitis-associated HLA-B*2705 presents a B*0702-restricted EBV epitope and sustains the clonal amplification of cytotoxic T cells in patients. AB - HLA-B*27 is strongly associated with an inflammatory autoimmune disorder, the Ankylosing Spondylitis (AS) and plays a protective role in viral infections. The two aspects might be linked. In this work, we compared in B*2705/B*07 positive patients with AS, the CD8+ T cell responses to two immunodominant EBV-derived epitopes restricted for either the HLA-B*27 (pEBNA3C) or the HLA-B*07 (pEBNA3A). We have unexpectedly found that the HLA-B*07-restricted EBNA3A peptide is presented by both the B*0702 and the B*2705 but not by the non AS-associated B*2709, that differs from the AS-associated B*2705 for a single amino acid in the peptide-binding groove (His116Asp). We then analysed 38 B*2705-positive/B*07 negative (31 AS-patients and 7 healthy donors) and 8 B*2709-positive/B*07 negative subjects. EBNA3A-specific CD8+ T lymphocytes were present in 55.3% of the HLA-B*2705 but in none of the B*2709 donors (p=0.0049). TCR beta-chain analysis identified common TCRBV and TCRBJ gene segments and shared CDR3beta sequences in pEBNA3A-responsive CTLs of B*2705 carriers, suggesting the existence of a shared TCR repertoire for recognition of the uncanonical B*2705/pEBNA3A complex. These data highlight the plasticity of the AS-associated HLA-B*2705, which presents peptides with suboptimal binding motifs, possibly contributing both to its enhanced capacity to protect against pathogens and to predispose to autoimmunity. PMID- 27254290 TI - UV-photodegradation of desipramine: Impact of concentration, pH and temperature on formation of products including their biodegradability and toxicity. AB - Desipramine (DMI) is a widely used tricyclic antidepressant, and it is the major metabolite of imipramine (IMI) and lofepramine (LMI); IMI and LMI are two of the most commonly used tricyclic antidepressants. If DMI enters the aquatic environment, it can be transformed by the environmental bacteria or UV radiation. Therefore, photolysis of DMI in water was performed using a simulated sunlight Xenon-lamp and a UV-lamp. Subsequently, the biodegradability of DMI and its photo transformation products (PTPs) formed during its UV photolysis was studied. The influence of variable conditions, such as initial DMI concentration, solution pH, and temperature, on DMI UV photolysis behavior was also studied. The degree of mineralization of DMI and its PTPs was monitored. A Shimadzu HPLC-UV apparatus was used to follow the kinetic profile of DMI during UV-irradiation; after that, ion-trap and high-resolution mass spectrometry coupled with chromatography were used to monitor and identify the possible PTPs. The environmentally relevant properties and selected toxicity properties of DMI and the non-biodegradable PTPs were predicted using different QSAR models. DMI underwent UV photolysis with first-order kinetics. Quantum yields were very low. DOC values indicated that DMI formed new PTPs and was not completely mineralized. Analysis by means of high resolution mass spectrometry revealed that the photolysis of DMI followed three main photolysis pathways: isomerization, hydroxylation, and ring opening. The photolysis rate was inversely proportional to initial DMI concentration. The pH showed a significant impact on the photolysis rate of DMI, and on the PTPs in terms of both formation kinetics and mechanisms. Although temperature was expected to increase the photolysis rate, it showed a non-significant impact in this study. Results from biodegradation tests and QSAR analysis revealed that DMI and its PTPs are not readily biodegradable and that some PTPs may be human and/or eco-toxic, so they may pose a risk to the environment. PMID- 27254291 TI - The Cooking and Pneumonia Study (CAPS) in Malawi: A Nested Pilot of Photovoice Participatory Research Methodology. AB - The Cooking and Pneumonia Study (CAPS) is a village-level randomised controlled trial of an advanced cookstove intervention to prevent pneumonia in children under the age of 5 in rural Malawi (www.capstudy.org). The trial offers a unique opportunity to gain understanding about the social and cultural factors that may facilitate sustained use of improved cookstoves. In January 2015, the use of Photovoice as a participatory research methodology was piloted at the CAPS Chikhwawa site. Photovoice is a photographic technique that allows communities (including women and marginalised groups) to share knowledge about their perspectives and priorities. Four households were given digital cameras and asked to collect images over 24-48 hours and were then interviewed on film about their selection. This resulted in over 400 images and a one hour long film that revealed community concerns and could be thematically analysed. The collection of interview data through film was useful for capturing discussion and was acceptable to participants. Photovoice is a feasible participatory research methodology that can play a valuable role in qualitative studies of improved cookstove adoption in challenging resource poor settings. PMID- 27254292 TI - The Temporal Order of Changes in Physical Activity and Subjective Sleep in Depressed Versus Nondepressed Individuals: Findings From the MOOVD Study. AB - Epidemiological studies have shown an association between physical activity and sleep, but it is unclear what the temporal order of this association is and whether it differs for depressed patients and healthy controls. Using a multiple repeated observations design, 27 depressed and 27 pair-matched nondepressed participants completed daily measurements of subjective sleep quality and duration during 30 consecutive days while an accelerometer continuously registered their physical activity. Changes in sleep duration, not quality, predicted next-day changes in physical activity (B = -0.21, p < .001), but not the other way around. Significant heterogeneity between individuals was observed, but the effect was not different for depressed and nondepressed participants. The findings underline the strength of a multiple repeated observations design in observational sleep research. PMID- 27254289 TI - Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic Review. AB - Alcoholic hepatitis (AH) occurs in about one-third of individuals reporting long term heavy alcohol use. It is associated with high short-term mortality, economic burden, and hospital resources utilization. We performed this systematic review to (i) describe clinical characteristics and genomics associated with the risk of AH; (ii) discuss role and limitations of liver biopsy and prognostic scoring systems; (iii) summarize evidence regarding the currently available therapies including liver transplantation; and (iv) outline emerging therapies with areas of unmet need. Literature search was performed for studies published in English language (January 1971 through March 2016). The following search engines were used: PubMed, Elsevier Embase, PsycINFO, and Cochrane Library. For the treatment section, only randomized controlled studies were included for this review. A total of 138 studies (59 randomized, 22 systematic reviews or meta-analyses, 7 surveys or guidelines, 7 population-based, and 43 prospective cohorts) were cited. There are over 325,000 annual admissions with AH contributing to about 0.8% of all hospitalizations in the United States. Liver biopsy may be required in about 25 to 30% cases for uncertain clinical diagnosis. Corticosteroids with or without N-acetylcysteine remains the only available therapy for severe episodes. Data are emerging on the role of liver transplantation as salvage therapy for select patients. Abstinence remains the most important factor impacting long-term prognosis. Results from the ongoing clinical trials within the National Institute on Alcohol Abuse and Alcoholism-funded consortia are awaited for more effective and safer therapies. AH is a potentially lethal condition with a significant short-term mortality. A high index of suspicion is required. There remains an unmet need for noninvasive biomarkers for the diagnosis, and predicting prognosis and response to therapy. PMID- 27254293 TI - A systematic review of motivational values and conservation success in and around protected areas. AB - In conservation projects in and around protected areas (PAs), a suite of policy instruments are used to promote conservation behavior in local people. Few studies have related psychological research on motivational values to conservation in PAs. We conducted a systematic review of 120 peer-reviewed articles to assess the relative frequencies of policy instruments that aimed to foster intrinsic versus extrinsic motivations to conserve. We examined how the type of motivation engendered by the instrument (i.e., intrinsic or extrinsic motivation and based on the description of how the project was designed and implemented) influenced the ecological, economic, and social success of the project. We assessed the success of the project in only the case studies that included a quantitative or qualitative analysis of success. Projects designed to foster at least one intrinsically motivating instrument were 3 times more likely to meet socioeconomic or ecological goals. Although certain types of instruments such as payments or fines tended to be based on extrinsic motivators more often than education or monitoring programs, several successful projects involving payments or fines were linked to intrinsic motivation in the local community. Thus, our results suggest that rather than debating the relative merits of specific types of policy instruments, conservationists may have more success by focusing on how different motivators, suited to specific contexts, can better empower local communities to conserve. Broadly, our results suggest the current emphasis on social justice and well-being of local communities is a positive step toward protecting the world's remaining biodiversity. PMID- 27254294 TI - Treatment of seafood processing wastewater using upflow microbial fuel cell for power generation and identification of bacterial community in anodic biofilm. AB - Tubular upflow microbial fuel cell (MFC) utilizing sea food processing wastewater was evaluated for wastewater treatment efficiency and power generation. At an organic loading rate (OLR) of 0.6 g d(-1), the MFC accomplished total and soluble chemical oxygen demand (COD) removal of 83 and 95%, respectively. A maximum power density of 105 mW m(-2) (2.21 W m(-3)) was achieved at an OLR of 2.57 g d(-1). The predominant bacterial communities of anode biofilm were identified as RB1A (LC035455), RB1B (LC035456), RB1C (LC035457) and RB1E (LC035458). All the four strains belonged to genera Stenotrophomonas. The results of the study reaffirms that the seafood processing wastewater can be treated in an upflow MFC for simultaneous power generation and wastewater treatment. PMID- 27254301 TI - Erratum: Reduced Graphene Oxide Thin Film on Conductive Substrates by Bipolar Electrochemistry. PMID- 27254302 TI - Isoform-specific targeting of ROCK proteins in immune cells. AB - Rho-associated kinase 1 (ROCK1) and ROCK2 are activated by Rho GTPase and control cytoskeleton rearrangement through modulating the phosphorylation of their down stream effector molecules. Although these 2 isoforms share more than 90% homology within their kinase domain the question of whether ROCK proteins function identically in different cell types is not clear. By using both pharmacological inhibition and genetic knockdown approaches recent studies suggest that the ROCK2 isoform plays an exclusive role in controlling of T-cell plasticity and macrophage polarization. Specifically, selective ROCK2 inhibition shifts the balance between pro-inflammatory and regulatory T-cell subsets via concurrent regulation of STAT3 and STAT5 phosphorylation, respectively. Furthermore, the administration of an orally available selective ROCK2 inhibitor effectively ameliorates clinical manifestations in experimental models of autoimmunity and chronic graft-vs.-host disease (cGVHD). Because ROCK2 inhibition results in the suppression of M2-type macrophages while favoring polarization of M1-type macrophages, ROCK2 inhibition can correct the macrophage imbalance seen during age-related macular degeneration (AMD). In summary, the exclusive role of ROCK2 in immune system modulation argues for the development and testing of isoform specific ROCK2 inhibitors for the treatment of inflammatory disorders. PMID- 27254303 TI - Catalytic Radical Reduction in Aqueous Solution by a Ruthenium Hydride Intermediate. AB - Some manganese complexes can catalyze both antioxidant and pro-oxidant reactions, whereby the disparate reactivity modes are determined by the catalyst environment and afford distinct therapeutic effects. We recently reported the reduction of radicals in buffered aqueous solution catalyzed by a ruthenium complex with biologically relevant non-tertiary alcohols as terminal reductants. Mechanistic evidence is presented, indicating that this catalytic radical reduction is achieved by a Ru-hydride intermediate formed by beta-hydride elimination from a Ru-alkoxide species. A similar mechanism and Ru-hydride intermediate was previously reported to kill cancer cells with catalytic pro-oxidant effects. Therefore, our demonstration of catalytic antioxidant effects by the same type of intermediate reveals new potential therapeutic strategies and applications for catalytic systems that form Ru-hydride intermediates. PMID- 27254304 TI - Biomembranes from slaughterhouse blood erythrocytes as prolonged release systems for dexamethasone sodium phosphate. AB - The present study investigated preparation of bovine and porcine erythrocyte membranes from slaughterhouse blood as bio-derived materials for delivery of dexamethasone-sodium phosphate (DexP). The obtained biomembranes, i.e., ghosts were characterized in vitro in terms of morphological properties, loading parameters, and release behavior. For the last two, an UHPLC/-HESI-MS/MS based analytical procedure for absolute drug identification and quantification was developed. The results revealed that loading of DexP into both type of ghosts was directly proportional to the increase of drug concentration in the incubation medium, while incubation at 37 degrees C had statistically significant effect on loaded amount of DexP (P < 0.05). The encapsulation efficiency was about fivefold higher in porcine compared to bovine ghosts. Insight into ghosts' surface morphology by field emission-scanning electron microscopy and atomic force microscopy confirmed that besides inevitable effects of osmosis, DexP inclusion itself had no observable additional effect on the morphology of the ghosts carriers. DexP release profiles were dependent on erythrocyte ghost type and amount of residual hemoglobin. However, sustained DexP release was achieved and shown over 3 days from porcine ghosts and 5 days from bovine erythrocyte ghosts. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1046 1055, 2016. PMID- 27254305 TI - Up-front Targeted Therapy Prior to Cytoreductive Nephrectomy in Treatment-Naive Patients With Metastatic Renal Cell Carcinoma. PMID- 27254306 TI - Rational Design of Porous Conjugated Polymers and Roles of Residual Palladium for Photocatalytic Hydrogen Production. AB - Developing highly efficient photocatalyts for water splitting is one of the grand challenges in solar energy conversion. Here, we report the rational design and synthesis of porous conjugated polymer (PCP) that photocatalytically generates hydrogen from water splitting. The design mimics natural photosynthetics systems with conjugated polymer component to harvest photons and the transition metal part to facilitate catalytic activities. A series of PCPs have been synthesized with different light harvesting chromophores and transition metal binding bipyridyl (bpy) sites. The photocatalytic activity of these bpy-containing PCPs can be greatly enhanced due to the improved light absorption, better wettability, local ordering structure, and the improved charge separation process. The PCP made of strong and fully conjugated donor chromophore DBD (M4) shows the highest hydrogen production rate at ~33 MUmol/h. The results indicate that copolymerization between a strong electron donor and weak electron acceptor into the same polymer chain is a useful strategy for developing efficient photocatalysts. This study also reveals that the residual palladium in the PCP networks plays a key role for the catalytic performance. The hydrogen generation activity of PCP photocatalyst can be further enhanced to 164 MUmol/h with an apparent quantum yield of 1.8% at 350 nm by loading 2 wt % of extra platinum cocatalyst. PMID- 27254307 TI - WSe2 nanoribbons: new high-performance thermoelectric materials. AB - In this work, for the first time, we systematically investigate the ballistic transport properties of WSe2 nanoribbons using first-principles methods. Armchair nanoribbons with narrow ribbon width are mostly semiconductive but the zigzag nanoribbons are metallic. Surprisingly, an enhancement in thermoelectric performance is discovered moving from monolayers to nanoribbons, especially armchair ones. The maximum room-temperature thermoelectric figure of merit of 2.2 for an armchair nanoribbon is discovered. This may be contributed to by the effects of the disordered edges, owing to the existence of dangling bonds at the ribbon edge. H-passivation has turned out to be an effective way to stabilize the edge atoms, which enhances the thermodynamic stability of the nanoribbons. In addition, after H-passivation, all of the armchair nanoribbons exhibit semiconductive properties with similar band gaps (~1.3 eV). Our work provides instructional theoretical evidence for the application of armchair WSe2 nanoribbons as promising thermoelectric materials. The enhancement mechanism of the disordered edge effect can also encourage further exploration to achieve outstanding thermoelectric materials. PMID- 27254308 TI - Proteomic profile of cerebrospinal fluid in patients with multiple sclerosis using two dimensional gel electrophoresis. PMID- 27254309 TI - The incidence rate and characteristics of clinically diagnosed defecatory disorders in the community. AB - BACKGROUND: Defecatory disorders (DD) are defined by clinical and objective features of impaired rectal evacuation. The epidemiology of DD in the population is unknown, partly because many constipated patients do not undergo anorectal tests. Our objectives were to estimate the incidence rate and clinical features of DD in the community. METHODS: We reviewed the medical records of all patients older than 16 years in Olmsted County, MN, who had constipation and underwent anorectal manometry from 1999 through 2008. Criteria for diagnosing DD were constipation for 6 months or longer and one of the following: (i) abnormal rectal balloon expulsion test; (ii) reduced or increased perineal descent; or (iii) two or more abnormal features with defecography or surface electromyography. KEY RESULTS: Of 11 112 constipated patients, 516 had undergone anorectal tests; 245 of these (209 women, 36 men) had a DD. The mean (+/-SD) age at diagnosis was 44 years (+/-18) among women and 49 years (+/-19) among men. The overall age- and sex-adjusted incidence rate per 100 000 person-years was 19.3 (95% CI: 16.8 21.8). The age-adjusted incidence per 100 000 person-years was greater (p < 0.0001) in women (31.8, 95% CI: 27.4-36.1) than in men (6.6, 95% CI: 4.4-8.9). Prior to the diagnosis of DD, nearly 30% of patients had irritable bowel syndrome (IBS), 48% had a psychiatric diagnosis, 18% had a history of abuse, and 21% reported urinary and/or fecal incontinence. CONCLUSIONS & INFERENCES: Among constipated patients, DD are fourfold more common in women than men and often associated with IBS and psychiatric diagnoses. PMID- 27254310 TI - Effect of D3 dopamine receptor on dopamine D4 receptor expression and function in renal proximal tubule cells from Wistar-Kyoto rats and spontaneously hypertensive rats. AB - BACKGROUND: Dopamine receptors induce natriuresis in kidney. Previous studies have shown interactions between different subtypes of dopamine receptors in renal proximal tubule (RPT) cells. We hypothesize that D3 receptors have an interaction with D4 receptors in RPT cells from normotensive rats (Wistar-Kyoto, WKY) and spontaneously hypertensive rats (SHRs). METHODS: Immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to examine the expression of D3 and D4 receptors. Na-K-ATPase activity was used to measure the function of receptors. The distribution and colocalization of D3 and D4 receptors were detected by confocal microscopy and co-immunoprecipitation. RESULTS: D3 receptor agonist PD128907 increased the mRNA and protein expression of D4 receptors in RPT cells from WKY rats, but decreased that from SHRs. In the presence of PLC blocker (U73122, 10-mol/l) or PKC inhibitor 19 -31 (10-mol/l), the up-regulation of D3 receptor on D4 receptor was lost in WKY cells. Moreover, stimulation with PD128907 for 30 minutes decreased D4 receptor degradation in WKY cells, not in SHR cells. D3 and D4 receptors colocalized and co immunoprecipitated in RPT cells. PD128907 increased co-immunoprecipitation of D3 and D4 receptors in WKY RPT cells, but not in SHR RPT cells. Pre-treatment with D3 receptor agonist also increases D4 receptor mediated inhibitory effect on Na-K ATPase activity in WKY cells, but not in SHR cells. CONCLUSION: Renal D3 receptor regulates the expression and function of D4 receptor in RPT cells via PLC /PKC signaling pathway, the loss of this interaction might be involved in the pathogenesis of hypertension. PMID- 27254311 TI - A high normal ankle-brachial index combined with a high pulse wave velocity is associated with cerebral microbleeds. AB - OBJECTIVES: Arterial stiffness is associated with the pathogenesis of cerebral microbleeds (CMBs). The ankle-brachial index (ABI) is used to predict arterial stiffness. We hypothesized that the increase in ABI with age occurs as a result of increasing arterial stiffness and wave reflection, and is thus associated with target organ damage. The aim of this study was to investigate the relationship between ABI, brachial-ankle pulse wave velocity (baPWV), and CMBs. METHODS: We recruited 990 cardiovascular disease-free and stroke-free participants [median age 53 (24-86) years, 531 were woman] who underwent brain MRI, ABI, and baPWV at a health checkup. RESULTS: The prevalence of CMBs was 4%. Both ABI (1.14 vs. 1.10) and baPWV (17.29 vs. 14.68 m/s) were higher in participants with CMBs than those without. Cutoff values of ABI and baPWV for the presence of CMBs were 1.12 and 16.07 m/s, respectively. Multivariate logistic regression analysis showed that ABI at least 1.12 [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.30 5.37, P < 0.05] and baPWV at least 16.07 m/s (OR 2.08, 95% CI 1.02-4.38, P < 0.05) were independently associated with CMBs. Moreover, the combination of ABI at least 1.12 and baPWV at least 16.07 m/s was strongly associated with CMBs (OR 5.26, 95% CI 1.93-16.92, P < 0.05). CONCLUSION: A high normal ABI, combined with a high baPWV, was strongly associated with CMBs in a screened Japanese cohort, suggesting a novel use for ABI as a predictor for target organ damage. PMID- 27254312 TI - Electrocardiographic left atrial abnormalities and risk of incident stroke in hypertensive patients with electrocardiographic left ventricular hypertrophy. AB - BACKGROUND: Recent findings in population-based studies suggest that abnormal P wave terminal force in lead V1 (PTFV1), a marker of left atrial abnormalities such as fibrosis, dilatation and elevated filling pressures, is associated with incident ischemic stroke, even in the absence of atrial fibrillation. However, whether PTFV1 predicts incident stroke in hypertensive patients during blood pressure lowering has not been examined. METHODS: Risk of incident stroke was examined in relation to abnormal PTFV1 on a baseline ECG in 7778 hypertensive patients with ECG left ventricular hypertrophy, no history of atrial fibrillation, in sinus rhythm on their baseline ECG with no incident atrial fibrillation during follow-up, who were randomly assigned to losartan-based or atenolol-based treatment. Results focused on the subset of patients between 55 and 60 years old (n = 1879) because of a significant interaction between PTFV1 and age in Cox analyses. Abnormal PTFV1 was defined by the presence of a negative terminal P wave in lead V1 with amplitude * duration >= 4000 MUV ms. RESULTS: During mean follow-up of 4.8 +/- 0.9 years, 364 patients (4.7%) of the overall study population and 45 patients (2.4%) in the subset of patients aged 60 years or less experienced a definite stroke. In the overall population, abnormal PTFV1 was not a significant predictor of incident stroke [hazard ratio 1.12, 95% confidence interval (CI) 0.91-1.38, P = 0.301], but there was a highly significant interaction of PTFV1 with age stratified at 60 (P = 0.009, hazard ratio 2.30, 95% CI 1.27-4.13, P = 0.006 for abnormal PTFV1 in the interaction model). Further analyses in the subset of patients aged 60 years or less revealed a higher incidence of stroke occurred in those with abnormal than normal baseline PTFV1: incidence rate per 1000 person-years, 7.8 (95% CI 5.2-11.4) vs 3.4 (95% CI 2.2-5.2; P = 0.004); a greater than two-fold increased risk of incident stroke (hazard ratio 2.31, 95% CI 1.28-4.16, P = 0.005) in univariate Cox analysis; and in multivariable Cox regression models that adjusted for other significant predictors of incident stroke in this population (sex, history of stroke or transient ischemic attack, ischemic heart disease or diabetes, baseline creatinine and in-treatment SBP), that abnormal PTFV1 remained associated with a greater than two-fold increased risk of incident stroke (hazard ratio 2.06; 95% CI 1.14-3.74, P = 0.017). CONCLUSION: Abnormal PTFV1, a marker of left atrial abnormality, was strongly associated with incident stroke in hypertensive patients, independent of in-treatment SBP and other predictors of incident stroke. This association, in the absence of detectable atrial fibrillation, suggests that an underlying atrial cardiopathy may cause left atrial thrombus formation and a subsequent stroke without intervening clinically recognized atrial fibrillation. PMID- 27254313 TI - Changes in albuminuria and cardiovascular risk under antihypertensive treatment: a systematic review and meta-regression analysis. AB - BACKGROUND: Increased urine albumin excretion (UAE) is a well known predictor of cardiovascular events in patients with primary hypertension. Whether a reduction in UAE is associated to an improvement in cardiovascular risk is at present unclear. We performed a systematic review and meta-regression analysis of available trials to investigate whether treatment-induced changes in UAE are related to cardiovascular outcome. METHODS: We searched MEDLINE, ISIWeb of Science, Cochrane Database and Scopus for studies including hypertensive patients, which reported cardiovascular events and UAE at baseline and at end of follow-up. RESULTS: In trials reporting pairwise comparisons between antihypertensive treatment for cardiovascular outcome (16 randomized controlled trials and 48 580 patients, mean follow-up 45 months, 5867 cardiovascular events) after adjustment for differences in achieved blood pressure, a relationship between changes in albuminuria and risk was evident in the presence of a relevant between-arms difference in albuminuria [relative risks (RR) pooled 0.45, confidence interval (CI) 0.23-0.85] but not when no improvement in UAE was found between randomized arms (RR pooled 1.04, 95% CI 0.86-1.26, P for difference between subgroups <0.001). Meta-regression analysis showed a relationship between changes in albuminuria and risk after adjustment for blood pressure variation under treatment (adj. coeff. 0.005, 95% CI 0.0005-0.0096, P = 0.033, R 34.8%). In studies reporting changes in cardiovascular events on the basis of UAE variations (six trials and 36 325 patients, mean follow-up 60 months, 3741 cardiovascular events), the overall adjusted RR of total cardiovascular events was 0.51 (95% CI 0.38-0.59, P = 0.000) for albuminuria regression/stable vs increase. CONCLUSION: Reduction in UAE under antihypertensive treatment is associated with reduced risk of clinical cardiovascular events. Our findings suggest that UAE changes may represent a valuable intermediate end point for cardiovascular events in primary hypertension. PMID- 27254314 TI - Thirty-Day Perioperative Outcomes in Pediatric Parotidectomy. AB - IMPORTANCE: Limited information exists about the short-term morbidity of parotidectomy in children. This information is important when counseling parents and planning treatment for children with parotid masses. OBJECTIVE: To examine 30 day perioperative outcomes after parotidectomy in the pediatric population. DESIGN, SETTING, AND PARTICIPANTS: A prospective case series of 87 pediatric patients who underwent parotidectomy from January 1, 2008, to June 30, 2015, performed by 2 pediatric head and neck specialists in a tertiary care pediatric hospital. MAIN OUTCOMES AND MEASURES: Thirty-day perioperative complications, postoperative facial nerve function, reoperation rates, and readmission rates were the main outcome measures. Secondary outcome measures were operative time and length of stay. RESULTS: Ninety parotidectomies (71 superficial and 19 total) were performed in 87 patients (48 male and 39 female). Mean age at operation was 8.3 years. Eighty-five of the cases (94%) were performed for benign disease. Mean operative time was 4.09 hours (range, 1.58-10.43 hours) and mean length of stay was 2.24 days (range, 0.97-4.33 days). Immediate postoperative facial weakness was observed in 32 cases (36%); 10 of these cases (31%) involved the upper branch and 29 (90%) involved the lower branch. Immediate postoperative paresis occurred more often after total parotidectomy vs superficial parotidectomy (11 of 19 [58%] vs 21 of 71 [30%]; P = .03) but was unrelated to the etiologic cause of the patients' parotid disease. Thirty of 32 cases (94%) of facial nerve weakness were transient, and the mean time to resolution was 61 days. Eleven complications (12%) other than facial nerve weakness occurred during the 30-day postoperative period. Three patients (3%) required a return to the operating room for hematoma or wound dehiscence. One patient (1%) required readmission in the 30-day postoperative period for contralateral parotitis. CONCLUSIONS AND RELEVANCE: We observed a low rate of 30-day perioperative complications as a result of superficial or total parotidectomy for pediatric parotid disease. Major adverse events included return to the operating room and 1 wound infection. Only 1 patient required readmission. Transient weakness of the facial nerve is relatively common, observed more often in the lower division, and can be expected to resolve in most patients by an average of 2 months. PMID- 27254315 TI - Accelerated MRI of the fetal heart using compressed sensing and metric optimized gating. AB - PURPOSE: To develop and validate a method for accelerated time-resolved imaging of the fetal heart using a combination of compressed sensing (CS) and metric optimized gating (MOG). THEORY AND METHODS: Joint optimization of CS and MOG reconstructions was used to suppress competing artifact from random undersampling and ungated cardiac motion. Retrospectively and prospectively undersampled adult and fetal data were used to validate the proposed reconstruction algorithm qualitatively based on visual assessment, and quantitatively based on reconstruction error, blur, and MOG timing error. RESULTS: Excellent agreement was observed between the fully sampled and retrospectively undersampled reconstructions, up to an undersampling factor of four. Visually, differences between ECG and MOG reconstructions of adult data were negligible. This was consistent with quantitative comparisons of reconstruction error (RMSEECG = 0.07 0.13; RMSEMOG = 0.08-0.13), and image blur (BECG = 1.03-1.20; BMOG = 1.03 1.20). The calculated MOG timing error (2-42 ms) was comparable to the acquired temporal resolution (~60 ms). Quantitative evaluation of retrospectively undersampled (R = 2-8) fetal data (RMSEMOG = 0.06-0.12; BMOG = 1.04-1.27) was comparable to the adult volunteer results. CONCLUSION: CS-MOG for dynamic imaging of the fetal heart was developed and validated. Using CS-MOG, images were obtained up to four times faster than conventional acquisitions. Magn Reson Med 77:2125-2135, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27254316 TI - P120-Catenin Regulates Early Trafficking Stages of the N-Cadherin Precursor Complex. AB - It is well established that binding of p120 catenin to the cytoplasmic domain of surface cadherin prevents cadherin endocytosis and degradation, contributing to cell-cell adhesion. In the present work we show that p120 catenin bound to the N cadherin precursor, contributes to its anterograde movement from the endoplasmic reticulum (ER) to the Golgi complex. In HeLa cells, depletion of p120 expression, or blocking its binding to N-cadherin, increased the accumulation of the precursor in the ER, while it decreased the localization of mature N-cadherin at intercellular junctions. Reconstitution experiments in p120-deficient SW48 cells with all three major isoforms of p120 (1, 3 and 4) had similar capacity to promote the processing of the N-cadherin precursor to the mature form, and its localization at cell-cell junctions. P120 catenin and protein tyrosine phosphatase PTP1B facilitated the recruitment of the N-ethylmaleimide sensitive factor (NSF), an ATPase involved in vesicular trafficking, to the N-cadherin precursor complex. Dominant negative NSF E329Q impaired N-cadherin trafficking, maturation and localization at cell-cell junctions. Our results uncover a new role for p120 catenin bound to the N-cadherin precursor ensuring its trafficking through the biosynthetic pathway towards the cell surface. PMID- 27254318 TI - Perfluoroalkylation of Unactivated Alkenes with Acid Anhydrides as the Perfluoroalkyl Source. AB - An efficient perfluoroalkylation of unactivated alkenes with perfluoro acid anhydrides was developed. Copper salts play a crucial role as a catalyst to achieve allylic perfluoroalkylation with the in situ generated bis(perfluoroacyl) peroxides. Furthermore, carboperfluoroalkylation of alkene bearing an aromatic ring at an appropriate position on the carbon side chain was found to proceed under metal-free conditions to afford carbocycles or heterocycles bearing a perfluoroalkyl group. This method, which makes use of readily available perfluoroalkyl sources, offers a convenient and powerful tool for introducing a perfluoroalkyl group onto an sp(3) carbon to construct synthetically useful skeletons. PMID- 27254319 TI - Intraocular Teratoid Medulloepithelioma Presenting With a Completely Rhabdomyosarcomatous Distant Metastasis. AB - IMPORTANCE: Medulloepithelioma is the second most common primary neuroepithelial tumor of the eye. The full range of its morphologic expressions and appearances in metastases have not been fully explored. OBSERVATIONS: A patient in her 50s with glaucoma for decades had undergone multiple filtering surgical procedures, including the placement of a glaucoma drainage device. A paraspinal mass was discovered, and tumor and bone marrow biopsies disclosed rhabdomyosarcoma. This led to the discovery of a multicystic intraocular tumor. A metastatic rhabdomyosarcoma to the eye was considered unlikely because, to our knowledge, this event had never been reported. An enucleation was performed, and an intraocular tumor composed almost entirely of rhabdomyoblasts (desmin- and myogenin-positive) was discovered along with rare clusters of persistent neuroepithelial cells. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first case of a medulloepithelioma in which teratoid rhabdomyoblasts effaced all but trace amounts of neuroepithelium and generated a distant metastasis entirely composed of rhabdomyoblasts. The prolonged history and filtering procedures probably led to these 2 phenomena. PMID- 27254317 TI - Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases. AB - Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut. PMID- 27254320 TI - Aqueous Growth of Gold Clusters with Tunable Fluorescence Using Photochemically Modified Lipoic Acid-Based Ligands. AB - We report a one-phase aqueous growth of fluorescent gold nanoclusters (AuNCs) with tunable emission in the visible spectrum, using a ligand scaffold that is made of poly(ethylene glycol) segment appended with a metal coordinating lipoic acid at one end and a functional group at the other end. This synthetic scheme exploits the ability of the UV-induced photochemical transformation of LA-based ligands to provide DHLA and other thiol byproducts that exhibit great affinity to metal nanoparticles, obviating the need for chemical reduction of the dithiolane ring using classical reducing agents. The influence of various experimental conditions, including the photoirradiation time, gold precursor-to-ligand molar ratios, time of reaction, temperature, and the medium pH, on the growth of AuNCs has been systematically investigated. The photophysical properties, size, and structural characterization were carried out using UV-vis absorption and fluorescence spectroscopy, TEM, DOSY-NMR, and X-ray photoelectron spectroscopy. The hydrodynamic size (RH) obtained by DOSY-NMR indicates that the size of these clusters follows the trend anticipated from the absorption and PL data, with RH(red) > RH(yellow) > RH(blue). The tunable emission and size of these gold nanoclusters combined with their high biocompatibility would make them greatly promising for potential use in imaging and sensing applications. PMID- 27254375 TI - Experience by children and adolescents of more than one type of maltreatment: Association of different classes of maltreatment profiles with clinical outcome variables. AB - Most victims of child abuse have experienced more than one type of maltreatment, yet there is a lack of understanding of the impact of specific combinations of types of maltreatment. This study aimed to identify meaningful classes of maltreatment profiles and to associate them with short-term clinical outcomes. A total of 358 German children and adolescents aged 4-17 with a known history of child maltreatment were included in the study. Through interviews and questionnaires, information was obtained from participants and their primary caregivers on history of maltreatment, sociodemographics, psychopathology, level of psychosocial functioning, and health-related quality of life. Types of abuse were categorized into six major groups: sexual abuse in general, sexual abuse with penetration, physical abuse, emotional abuse, neglect, and exposure to domestic violence. A latent class analysis (LCA) was performed to determine distinct multi-type maltreatment profiles, which were then assessed for their associations with the sociodemographic and clinical outcome variables. The LCA revealed that participants could be categorized into three meaningful classes according to history of maltreatment: (1) experience of multiple types of maltreatment excluding sexual abuse (63.1%), (2) experience of multiple types of maltreatment including sexual abuse (26.5%), and (3) experience of predominantly sexual abuse (10.3%). Members of Class 2 showed significantly worse short-term outcomes on psychopathology, level of functioning, and quality of life compared to the other classes. Three distinct profiles of multiple types of maltreatment were empirically identified in this sample. Exposure to multiple types of abuse was associated with poorer outcomes. PMID- 27254376 TI - Disposition of emergency department patients diagnosed with acute heart failure: an international emergency medicine perspective. AB - Many patients with acute heart failure are initially managed in emergency departments (EDs) worldwide. Although some require hospitalization for further management, it is likely that a sizeable proportion could be safely discharged either directly from the ED or after a more extended period of management in an observation-type unit. Identification of low-risk patients who are safe for such an approach to management continues to be a global unmet need. This is driven in part by a lack of clarity on postdischarge outcomes for lower risk patients and a nonexistent consensus on what may be acceptable event rates. The current paper reviews previous studies carried out on patients directly discharged from the ED, suggests a general disposition algorithm and focuses on discharge metrics, which are based on both evidence and expert opinion. In addition, we propose that the following variables be considered for future determination of acceptable event rates: (a) baseline characteristics and risk status of the patient; (b) access to follow-up; PMID- 27254377 TI - Chemotherapy: Response and Survival Data #99. PMID- 27254379 TI - Interleukin-33, friend and foe in type-2 immune responses. AB - IL-33 is the most recent addition to the IL-1 cytokine family, identified in 2005 as the ligand of T1/ST2 and inducer of type-2 immune responses. IL-33 has been implicated in a wide range of disease settings, in anti-inflammatory responses and homeostasis, and thus signalling must be strictly regulated. Altered gene expression, post-translational modification, decoy receptor, and receptor signalling are all modulatory mechanisms used to control the IL-33 pathway. Understanding both the genetic and post-translational factors influencing IL-33 activity will be critical for provision of safe effective treatment of type-2 disorders. PMID- 27254380 TI - Childhood allergies and asthma: New insights on environmental exposures and local immunity at the lung barrier. AB - While certain bacteria and respiratory viruses promote local inflammation and disease onset, a more diverse colonization of the different species in the (gut) microbiome may be linked to more regulatory responses and protection against asthma and allergies. These processes are also influenced in part by food intake, both targeting the composition of the gut microbiome and influencing the immune system via metabolites. Early life environmental microbial exposure also contributes to protection against asthma and allergy and is linked with an early activation of the innate immune system and the development of regulatory immune responses. Although greater mechanistic insight is needed, it is tempting to speculate that part of the environmental effect can be explained by modulation of the microbiome composition at mucosal surfaces, epithelial barrier function and/or local immunity. A review of the latest studies is provided. PMID- 27254381 TI - The self-assembly of copolymers with one hydrophobic and one polyelectrolyte block in aqueous media: a dissipative particle dynamics study. AB - The reversible self-assembly of symmetrical block copolymers consisting of one hydrophobic block and one ionizable polyelectrolyte block of the same length has been studied in aqueous solutions by dissipative particle dynamics simulations. In addition to three standard dissipative particle dynamics forces (conservative soft repulsion, dissipative and stochastic forces), explicit interaction between smeared charges on ions and on ionized polymer beads described by the electrostatic potential with appropriately localized charges was taken into account. The self-assembly and properties of formed core-shell micelles were investigated as functions of the degree of ionization for systems differing in the hydrophobicity of the non-ionized polyelectrolyte block and in the compatibility of the polymer blocks. This study shows that micelles undergo massive dissociation with increasing degree of ionization. The simulation data compare well with the predictions of scaling theories for systems with soluble polyelectrolytes on a semi-quantitative level and broaden the knowledge of systems in poor solvents. PMID- 27254382 TI - Tuning the Protein Corona of Hydrogel Nanoparticles: The Synthesis of Abiotic Protein and Peptide Affinity Reagents. AB - Nanomaterials, when introduced into a complex, protein-rich environment, rapidly acquire a protein corona. The type and amount of proteins that constitute the corona depend significantly on the synthetic identity of the nanomaterial. For example, hydrogel nanoparticles (NPs) such as poly(N-isopropylacrylamide) (NIPAm) have little affinity for plasma proteins; in contrast, carboxylated poly(styrene) NPs acquire a dense protein corona. This range of protein adsorption suggests that the protein corona might be "tuned" by controlling the chemical composition of the NP. In this Account, we demonstrate that small libraries of synthetic polymer NPs incorporating a diverse pool of functional monomers can be screened for candidates with high affinity and selectivity to targeted biomacromolecules. Through directed synthetic evolution of NP compositions, one can tailor the protein corona to create synthetic organic hydrogel polymer NPs with high affinity and specificity to peptide toxins, enzymes, and other functional proteins, as well as to specific domains of large proteins. In addition, many NIPAm NPs undergo a change in morphology as a function of temperature. This transformation often correlates with a significant change in NP-biomacromolecule affinity, resulting in a temperature-dependent protein corona. This temperature dependence has been used to develop NP hydrogels with autonomous affinity switching for the protection of proteins from thermal stress and as a method of biomacromolecule purification through a selective thermally induced catch and release. In addition to temperature, changes in pH or buffer can also alter a NP protein corona composition, a property that has been exploited for protein purification. Finally, synthetic polymer nanoparticles with low nanomolar affinity for a peptide toxin were shown to capture and neutralize the toxin in the bloodstream of living mice. While the development of synthetic polymer alternatives to protein affinity reagents is in its early stages, these recent successes using only small libraries of functional monomers are most encouraging. It is likely that by expanding the chemical diversity of functional hydrogels and other polymers, a much broader range of NP-biomacromolecule affinity pairs will result. Since these robust, nontoxic polymers are readily synthesized in the chemistry laboratory, we believe the results presented in this Account offer a promising future for the development of low cost alternatives to more traditional protein affinity reagents such as antibodies. PMID- 27254383 TI - A Facile Strategy to Fabricate Multishape Memory Polymers with Controllable Mechanical Properties. AB - A facile blending strategy to fabricate multishape memory polymers (SMPs) with only one sort of phase transition material has been reported. In this work, olefin block copolymer (OBC) and styrene-b-(ethylene-co-butylene)-b-styrene (SEBS), which are both physically crosslinked, are blended with crystalline paraffin together. Due to the different interactions between polymer matrices and paraffin, the paraffin penetrated in OBC and SEBS exhibit separated melting transitions. It is quite interesting that merely paraffin distributed in OBC also shows two distinct melting transitions with enough OBC content in composites. Therefore, excellent quadruple shape memory effect can be achieved with a maximum of three melting transitions. Furthermore, through adjusting the polymer species and content, the mechanical and rheological properties can be conveniently tuned to a great extent. Compared with the reported strategies, this simple and controllable method sheds light on rapid design of multi-SMPs using inexpensive raw materials, which greatly paves the way for multi-SMPs from laboratory to factory. PMID- 27254384 TI - Bacterial community dynamics in long-term operation of a pilot plant using aerobic granular sludge to treat pig slurry. AB - Aerobic granular sludge represents an interesting approach for simultaneous organic matter and nitrogen removal in wastewater treatment plants. However, the information about microbial communities in aerobic granular systems dealing with industrial wastewater like pig slurry is limited. Herein, bacterial diversity and dynamics were assessed in a pilot scale plant using aerobic granular sludge for organic matter and nitrogen elimination from swine slurry during more than 300 days. Results indicated that bacterial composition evolved throughout the operational period from flocculent activated sludge, used as inoculum, to mature aerobic granules. Bacterial diversity increased at the beginning of the granulation process and then declined due to the application of transient organic matter and nitrogen loads. The operational conditions of the pilot plant and the degree of granulation determined the microbial community of the aerobic granules. Brachymonas, Zoogloea and Thauera were attributed with structural function as they are able to produce extracellular polymeric substances to maintain the granular structure. Nitrogen removal was justified by partial nitrification (Nitrosomonas) and denitrification (Thauera and Zoogloea), while Comamonas was identified as the main organic matter oxidizing bacteria. Overall, clear links between bacterial dynamics and composition with process performance were found and will help to predict their biological functions in wastewater ecosystems improving the future control of the process. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1212-1221, 2016. PMID- 27254385 TI - A Value-Critical Choice Analysis of a Policy to Prevent Suicide in Veterans and Service Members. AB - A few years after the advent of the Global War on Terror, veteran and service member suicide emerged on the national forefront as a public health issue of significant concern. This social policy analysis applies a value-critical choice model to the military suicide prevention provisions mandated by Section 2 of Exec. Order No. 13625 (2012): Improving Access to Mental Health Services for Veterans, Service Members, and Military Families. Results reveal that the suicide prevention provisions mandated by the order have not been fully and effectively implemented and the goal of reducing military suicide remains elusive. PMID- 27254386 TI - Corrigendum: Prognostic role of Gli1 expression in solid malignancies: a meta analysis. PMID- 27254387 TI - Cyano-decorated ligands: a powerful alternative to fluorination for tuning the photochemical properties of cyclometalated Ir(iii) complexes. AB - A new cyclometalating ligand, featuring nitrile moieties to enhance the photophysical and consequently photocatalytic properties of bis-cyclometalated Ir(iii) complexes, was synthesized. Nitrile moieties were selected to replace expensive and environmentally problematic fluoride moieties commonly employed for synthetic tuning of chromophores. Two new chromophores bearing the new nitrile decorated ligand were synthesized with strong electron-donating and electron withdrawing ancillary ligands to probe extremes of the complexes' tunability. These complexes possessed rich and drastically different electrochemical and photophysical properties. One chromophore possessed a particularly long lifetime of approximately 8 MUs; it was also a remarkably efficient triplet emitter with a quantum yield of 63%. The complexes were finally assessed as photosensitizers of water reduction with Pt colloids, where both complexes produced hydrogen with optimized conditions reaching 2000 and 1400 turnovers. PMID- 27254388 TI - A New Way to See a Bronchopleural Fistula. PMID- 27254389 TI - Sculpting infant soothability: the role of prenatal SSRI antidepressant exposure and neonatal SLC6A4 methylation status. AB - The role of prenatal Selective Serotonin Reuptake Inhibitor (SSRI) exposure and SLC6A4 promoter methylation status in shaping soothability at 3 and 6 months of age, for infants exposed to antidepressant medication prenatally (n = 46) and those not exposed (n = 69) was investigated. SSRI exposure status and duration of exposure (number of days) were examined along with neonatal methylation status at mean CpG 9,10 and via factor analysis across 10 CpG sites yielding PC1 (CpGs sites: 3,4,5,7) and PC2 (CpG 1,8). Analyses revealed interactions for methylation markers and SSRI exposure variables. A significant interaction between SSRI exposure and mean SLC6A4 methylation at CpG 9,10 and separately for PC1 emerged, controlling for multiple birth/medical and background covariates (e.g., Apgar scores, maternal education). Increased neonatal methylation status was associated with increased soothability changes from 3 to 6 months among infants prenatally exposed to SSRIs. PMID- 27254390 TI - Direct Measurement of the Electrical Abruptness of a Nanowire p-n Junction. AB - Electrostatic potential maps of GaAs nanowire, p-n junctions have been measured via off-axis electron holography and compared to results from in situ electrical probing, and secondary electron emission microscopy using scanning electron microscopy. The built-in potential and depletion length of an axial junction was found to be 1.5 +/- 0.1 V and 74 +/- 9 nm, respectively, to be compared with 1.53 V and 64 nm of an abrupt junction of the same end point carrier concentrations. Associated with the switch from Te to Zn dopant precursor was a reduction in GaAs nanowire diameter 3 +/- 1 nm that occurred prior to the junction center (n = p) and was followed by a rapid increase in Zn doping. The delay in Zn incorporation is attributed to the time required for Zn to equilibrate within the Au catalyst. PMID- 27254392 TI - Dengue and other Aedes-borne viruses: a threat to Europe? PMID- 27254391 TI - Analytical Inverse Optimization in Two-Hand Prehensile Tasks. AB - The authors explored application of analytical inverse optimization (ANIO) method to the normal finger forces in unimanual and bimanual prehensile tasks with discrete and continuously changing constraints. The subjects held an instrumented handle vertically with one or two hands. The external torque and grip force changed across trials or within a trial continuously. Principal component analysis showed similar percentages of variance accounted for by the first two principal components across tasks and conditions. Compared to unimanual tasks, bimanual tasks showed significantly more frequent inability to find a cost function leading to a stable solution. In cases of stable solutions, similar second-order polynomials were computed as cost functions across tasks and condition. The bimanual tasks, however, showed significantly worse goodness-of fit index values. The authors show that ANIO can be used in tasks with slowly changing constraints making it an attractive tool to study optimality of performance in special populations. They also show that ANIO can fail in multifinger tasks, likely due to irreproducible behavior across trials, more likely to happen in bimanual tasks compared to unimanual tasks. PMID- 27254393 TI - Lag-length effect on repetition priming of famous and unfamiliar faces: evidence from N250r and N400. AB - Previous event-related potentials research has reliably identified two repetition priming components in faces, the N250r and the N400, which are believed to reflect, respectively, the accessing to the stored structural representations and the semantic retrieval. However, the effect of lags longer than immediate repetition and shorter than 3 min on the two components has not been described as yet, and the interaction between lag length and familiarity is unclear. The current experiment aims to address these issues. In this experiment, famous and unfamiliar faces were represented after short, medium, or long lags, and participants were required to decide whether each face was known or not. The data showed that the frontal N250r, rather than the temporal counterpart, persisted to the medium lag case for famous faces; for unfamiliar faces, no N250r was observed. The frontal N400 was more regulated by lag length than the centroparietal counterpart. These results suggest that the frontal N250r and the frontal N400 are affected by the lag length; moreover, the former is more sensitive to the pre-experimental familiarity of faces. PMID- 27254394 TI - Visual evoked potentials to an illusory change in brightness: the Craik-Cornsweet O'Brien effect. AB - Can brain electrical activity associated with the Craik-Cornsweet-O'Brien effect (CCOB) be identified in humans? Opposing luminance gradients met in the middle of a square image to create a luminance contrast-defined vertical border. The resulting rectangles on each side of the border were otherwise equiluminant, but appeared to differ in brightness, the CCOB effect. When the contrast gradients were swapped, the participants perceived darker and lighter rectangles trading places. This dynamic CCOB stimulus was reversed 1/s to elicit visual evoked potentials. The CCOB effect was absent in two control conditions. In one, the immediate contrast border, where the gradients met, was replaced by a dark vertical stripe; in the other, the outer segments of both rectangles, where the illusion would otherwise occur, were replaced by dark rectangles, leaving only the contrast-reversing gradients. Visual evoked potential components P1 and N2 were present for the CCOB stimuli, but not the control stimuli. Results are consistent with functional MRI and single unit evidence, suggesting that the brightness of the CCOB effect becomes dissociated from the luminance falling on the eye early in visual processing. These results favor explanations of brightness induction invoking rapid, early amplification of very low spatial frequency information in the image to approximate natural scenes as opposed to a sluggish brightness adjustment spreading from the contrast border. PMID- 27254395 TI - Effect of photon induced photoacoustic streaming (PIPS) on bond strength to dentine of two root canal filling materials. AB - OBJECTIVES: The aim of this study was to evaluate the effect of photon induced photoacoustic streaming (PIPS) technique in combination with EDTA on bond strength of gutta-percha/AH Plus and Resilon/RealSeal SE root canal fillings to root dentine. MATERIALS AND METHODS: Forty freshly extracted human maxillary anterior teeth with intact straight roots, were instrumented endodontically with rotating ProTaper instruments and randomly divided into two experimental groups. In group 1 (n = 20), root canals were rinsed for 1 minute with 2 ml of 17% EDTA. In group 2 (n = 20), Er:YAG laser, with a 14 mm long 400 MU diameter tapered PIPS tip, was used for 1 minute with 2 ml of 17% EDTA. The laser parameters used were: 20 mJ per pulse, 15 Hz, 50 microsecond. In each experimental group, half of the root canals (n = 10) were obturated with gutta-percha/AH Plus and other half (n = 10) with Resilon/RealSeal SE. A micropush-out test was performed on sectiond specimens of the filled roots using a universal testing machine and resistance to failure plus failure modes were determined. RESULTS: Both gutta-percha/AH Plus groups had higher bond strength to root dentin than the Resilon/RealSeal SE groups (P < 0.05). The smear layer removal protocol, with EDTA only or combining PIPS technique with EDTA, had no influence on bond strength of either gutta percha/AH Plus, or Resilon/RealSeal SE (P > 0.05). CONCLUSION: Within the limitations of this study, it was found that the application of the PIPS technique did not have an affect on the push-out bond strength of Resilon/RealSeal SE root canal filling to dentin nor on the gutta-percha/AH Plus. A significant difference in bond strength was noted between the two root canal filling materials. Lasers Surg. Med. 48:951-954, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27254396 TI - Notes from the Field: Investigation of Hepatitis C Virus Transmission Associated with Injection Therapy for Chronic Pain - California, 2015. AB - On November 26, 2014, the California Department of Public Health (CDPH) contacted CDC concerning a report from the Santa Barbara County Public Health Department (SBPHD) regarding acute hepatitis C virus (HCV) infection in a repeat blood donor. The patient, who was asymptomatic, was first alerted of the infection by the blood bank and had no traditional risk factors for HCV infection. The donor had a negative HCV nucleic acid test (NAT) 56 days before the first positive NAT test, and an investigation into the donor's health care exposures and other potential risk factors, including injection drug use, incarceration, and long term hemodialysis within this narrow exposure window, was conducted by SBPHD. PMID- 27254397 TI - Wafer-Scale Nanopillars Derived from Block Copolymer Lithography for Surface Enhanced Raman Spectroscopy. AB - We report a novel nanofabrication process via block copolymer lithography using solvent vapor annealing. The nanolithography process is facile and scalable, enabling fabrication of highly ordered periodic patterns over entire wafers as substrates for surface-enhanced Raman spectroscopy (SERS). Direct silicon etching with high aspect ratio templated by the block copolymer mask is realized without any intermediate layer or external precursors. Uniquely, an atomic layer deposition (ALD)-assisted method is introduced to allow reversing of the morphology relative to the initial pattern. As a result, highly ordered silicon nanopillar arrays are fabricated with controlled aspect ratios. After metallization, the resulting nanopillar arrays are suitable for SERS applications. These structures readily exhibit an average SERS enhancement factor of above 10(8), SERS uniformities of 8.5% relative standard deviation across 4 cm, and 6.5% relative standard deviation over 5 * 5 mm(2) surface area, as well as a very low SERS background. The as-prepared SERS substrate, with a good enhancement and large-area uniformity, is promising for practical SERS sensing applications. PMID- 27254398 TI - Acoustic radiation force and torque exerted on a small viscoelastic particle in an ideal fluid. AB - We provide a detailed analysis on the acoustic radiation force and torque exerted on a homogeneous viscoelastic particle in the long-wave limit (i.e. the particle radius is much smaller than the incident wavelength) by an arbitrary wave. We assume that the particle behaves as a linear viscoelastic solid, which obeys the fractional Kelvin-Voigt model. Simple analytical expressions for the radiation force and torque are obtained. The developed theory is used to describe the interaction of acoustic waves (traveling and standing plane waves, and zero- and first-order Bessel beams) in the MHz-range with polymeric particles, namely lexan, low-density (LDPE) and high-density (HDPE) polyethylene. We found that particle absorption is chiefly the cause of the radiation force due to a traveling plane wave and zero-order Bessel beam when the frequency is smaller than 5MHz (HDPE), 3.9MHz (LDPE), and 0.9MHz (lexan). Whereas in a standing wave field, the radiation force is mildly changed due to dispersion inside the particle. We also show that the radiation torque caused by a first-order Bessel beam varies nearly quadratic with frequency. These findings may enable new possibilities of particle handling in acoustophoretic techniques. PMID- 27254400 TI - New approaches on the study of the psychometric properties of the STAI. AB - INTRODUCTION: The main purpose of this study was to analyze the psychometric properties of the State-Trait Anxiety Inventory (STAI1). Previous studies have indicated different factor solutions. Nevertheless, there is still a lack of consensus about the best dimensional model of STAI scores. METHOD: The sample consisted of 417 participants, composed of 387 (29.71% male) healthy participants (comparison group: M=35.5 years; SD=8.40), and 30 (36.66% male) patient (clinical group M=35.8 years; SD=12.94). RESULTS: The internal consistency evaluated through Ordinal Alpha was good, 0.98 and 0.94 in the non-clinical and the clinical samples, respectively. Test-retest reliability (two weeks) for Total Score was 0.81 for the non-clinical subsample, and 0.93 for the clinical subsample. Confirmatory factor analyses supported both a four factor model and bifactor model. Also, STAI scores showed statistically significant correlations with Burns Anxiety Inventory (Burns-A) scores. Furthermore, results showed statistically significant differences in the mean scores of the STAI between the clinical and the non-clinical subsamples. CONCLUSIONS: The psychometric properties of the STAI were adequate. The present study contributes to better understand the STAI structure through the comparison of new approaches in the study of the STAI internal structure. The results found may contribute in the efforts to improve the evaluation and identification of anxiety symptoms and disorders. PMID- 27254399 TI - Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy. AB - INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive neurostimulation technique that is able to induce neuromodulatory effects outlasting the duration of the stimulation train. The cortical excitability disturbance in epilepsy provides a rationale for investigating the efficacy of low-frequency rTMS as a treatment for epilepsy patients. Sofar clinical trials in epilepsy patients have shown conflicting results ranging from ineffective to very effective. AREAS COVERED: This manuscript provides an overview of the performed studies, retrieved from a PubMed search, and a critical appraisal of their results. A number of conclusions are drawn and potential optimization strategies are discussed. Expert commentary: Although the therapeutic efficacy of rTMS in refractory epilepsy has not yet been established, the non-invasiveness of the technique warrants further investigation of rTMS as a treatment for epilepsy. PMID- 27254401 TI - Fluoxetine, topiramate, and combination of both to stabilize eating behavior before bariatric surgery. AB - INTRODUCTION: Pharmacotherapy for the management of obesity is primarily aimed at weight loss, weight loss maintenance and risk reduction (reduction in body fat, risk factors for cardiovascular disease and the incidence of diabetes mellitus). Among drugs that have been evaluated for weight loss include antidepressants (fluoxetine) and antiepileptic (topiramate). MATERIAL AND METHODS: We analyzed eating behavior and weight loss in a sample of morbid obesity patients before bariatric surgery. The patients suffering eating disturbances symptoms were grouped into three groups: one group received 40 mg of flouxetine/day (Group A); another group received topiramate 200 mg/day (Group B); and the third group of patients were treated with fluoxetine 40 mg and 200 mg of topiramate/day (Group C). RESULTS: Patients treated with fluoxetine plus topiramate lost more weight at 3 and 6 months before surgery. CONCLUSIONS: The use of the psychopharmaceutical drug (fluoxetine and topiramate) in morbid obese patients with eating disorders could represent a new approach to the management of eating behavior before bariatric surgery. PMID- 27254402 TI - Is it possible to achieve functional recovery in schizophrenia? A qualitative and quantitative analysis of psychiatrist´s opinion. AB - INTRODUCTION: Psychiatrist´s opinion on functional recovery (FR) of patients with schizophrenia may modulate the therapeutic expectations and how to manage the disease. OBJECTIVE: This study aims to know the opinion of psychiatrists on FR, and to analyze the relationship between functioning and symptoms. METHODS: A qualitative and quantitative, descriptive and exploratory study. Two data collection techniques were used: a) a written survey consisting of 12 questions, directly, anonymously and confidentially answered by 132 psychiatrists; b) 5 focus group discussions involving 42 psychiatrists. RESULTS: 69.8% of psychiatrists considered realistic to get FR in schizophrenia and another 30.1% chose an intermediate response. The clinical priority for the 94% is to optimize the functional outcome of their patients, but only 14.4% commonly use rating scales. 91.7 % believed that there are differences between typical and atypical antipsychotics in terms of FR, and 83.3% believed essential to implement psychosocial interventions to achieve this goal. According to psychiatrists, FR is a complex concept and a primary therapeutic goal. Negative and cognitive symptoms are the strongest predictors of poor functioning. The low functioning of a patient, even in symptomatic stability, usually requires a re-evaluation of treatment. CONCLUSION: For psychiatrists, FR is a useful concept and a clinical priority, although there are doubts about how to achieve it. PMID- 27254403 TI - Mechanism of action of guanfacine: a postsynaptic differential approach to the treatment of attention deficit hyperactivity disorder (adhd). AB - The treatment of ADHD has focused on the use of psychostimulants drugs such as methylphenidate or amphetamine and derivatives, or not stimulants agents, such as atomoxetine. These agents act mainly on catecholaminergic presynaptic mechanisms. Recently the European Medicines Agency (EMA) has approved another not psychostimulant drug, guanfacine extended release (ER), as a new option to the treatment of ADHD, which acts at postsynaptic level. Guanfacine stimulates postsynaptic alfa-2A adrenergic receptors so it inhibits the production of cAMP and closes HCN channels enhancing the effectiveness of the signal of the pyramidal neurons of the prefrontal cortex (PFC), thus improving working memory and attention. In addition, stimulation of the alpha-2A receptors promotes growth and maturation of the dendritic spines of pyramidal neurons of the medial PFc, that are associated with brain function such as learning and memory. In contrast with psychostimulants or atomoxetine, guanfacine mimics noradrenaline stimulation of postsynaptic receptors alfa-2A on the PFC. PMID- 27254404 TI - Impulsivity and executive function in borderline personality disorder. PMID- 27254405 TI - Between the sanitary complacency and the factitious disorder by proxy. PMID- 27254407 TI - Endotoxin hitchhiking on polymer nanoparticles. AB - The control of microbial infections is critical for the preparation of biological media including water to prevent lethal septic shock. Sepsis is one of the leading causes of death in the United States. More than half a million patients suffer from sepsis every year. Both gram-positive and gram-negative bacteria are responsible for septic infection by the most common organisms i.e., Escherichia coli and Pseuodomonas aeruginosa. The bacterial cell membrane releases negatively charged endotoxins upon death and enzymatic destruction, which stimulate antigenic response in humans to gram-negative infections. Several methods including distillation, ethylene oxide treatment, filtration and irradiation have been employed to remove endotoxins from contaminated samples, however, the reduction efficiency remains low, and presents a challenge. Polymer nanoparticles can be used to overcome the current inability to effectively sequester endotoxins from water. This process is termed endotoxin hitchhiking. The binding of endotoxin on polymer nanoparticles via electrostatic and hydrophobic interactions offers efficient removal from water. However, the effect of polymer nanoparticles and its surface areas has not been investigated for removal of endotoxins. Poly(epsilon-caprolactone) (PCL) polymer was tested for its ability to effectively bind and remove endotoxins from water. By employing a simple one-step phase separation technique, we were able to synthesize PCL nanoparticles of 398.3 +/- 95.13 nm size and a polydispersity index of 0.2. PCL nanoparticles showed ~78.8% endotoxin removal efficiency, the equivalent of 3.9 * 10(5) endotoxin units (EU) per ml. This is 8.34-fold more effective than that reported for commercially available membranes. Transmission electron microscopic images confirmed binding of multiple endotoxins to the nanoparticle surface. The concept of using nanoparticles may be applicable not only to eliminate gram-negative bacteria, but also for any gram-positive bacteria, fungi and parasites. PMID- 27254408 TI - Hb Tianshui (HBB: C.119A > G) in Compound Heterozygosity with Hb S (HBB: C.20A > T) from Odisha, India. AB - We describe here a rare beta-globin gene variant, Hb Tianshui [beta39(C5)Glu >Arg; HBB: c.119A > G], detected during routine screening in Odisha, India. This is the second report of Hb Tianshui and the first to describe the cation exchange high performance liquid chromatography (HPLC) and DNA studies of two cases of this variant. Both cases had coinherited Hb S (HBB: c.20A > T) but none presented with typical symptoms of sickle cell disease. One of the cases was heterozygous for a common alpha-thalassemia (alpha-thal) allele (-alpha(3.7)) (rightward) (NG_000006.1: g.34164_37967del3804) and marginally raised Hb F percentage, while the other Hb S/Hb Tianshui case was completely benign and healthy. An atypical Asian Indian haplotype [+ - + - +] could be assigned to the Hb Tianshui variant. Hb Tianshui seems to mimic a few other Hb variants in cation exchange HPLC. However, we report two specific patterns in the chromatograms that are characteristic to Hb Tianshui. Combining an alkaline electrophoresis result with cation exchange HPLC at screening would be preferred to detect this rare variant, especially in regions with considerable frequency of Hb E [beta26(B8)Glu->Lys; HBB: c.79G > A] or Hb S. PMID- 27254409 TI - Pharmacotherapy for comorbidities in chronic heart failure: a focus on hematinic deficiencies, diabetes mellitus and hyperkalemia. AB - INTRODUCTION: Chronic heart failure (HF) is frequently accompanied by one or more comorbidities. The presence of comorbidities in chronic HF is strongly correlated to HF severity and impaired outcome. AREAS COVERED: This review will address several comorbidities with high prevalence and/or high impact in patients with chronic HF, including diabetes, anemia, hematinic deficiencies, and hyperkalemia. The background and subsequent pharmacotherapeutic options of these comorbidities will be discussed. For this review, a MEDLINE search was performed. EXPERT OPINION: Heart failure is increasingly considered a multimorbid syndrome, including metabolic derangements and chronic inflammation. Persistent metabolic derangements and low-grade inflammation might lead to progression of HF and the development of comorbidities. Although several comorbidity-specific drugs became available in the past decade, most of these therapies are studied in relatively small cohorts using surrogate end-points. Therefore, larger studies are needed to address whether treating these comorbidities will improve patient outcome in chronic HF. PMID- 27254410 TI - Correction: Cerebral Glioma Grading Using Bayesian Network with Features Extracted from Multiple Modalities of Magnetic Resonance Imaging. AB - [This corrects the article DOI: 10.1371/journal.pone.0153369.]. PMID- 27254411 TI - Stress and the Microbiota-Gut-Brain Axis: An Evolving Concept in Psychiatry. PMID- 27254412 TI - Posttraumatic Stress Disorder: Does the Gut Microbiome Hold the Key? AB - Gut bacteria strongly influence our metabolic, endocrine, immune, and both peripheral and central nervous systems. Microbiota do this directly and indirectly through their components, shed and secreted, ranging from fermented and digested dietary and host products to functionally active neurotransmitters including serotonin, dopamine, and gamma-aminobutyric acid. Depression has been associated with enhanced levels of proinflammatory biomarkers and abnormal responses to stress. Posttraumatic stress disorder (PTSD) appears to be marked in addition by low cortisol responses, and these factors seem to predict and predispose individuals to develop PTSD after a traumatic event. Dysregulation of the immune system and of the hypothalamic-pituitary-adrenal axis observed in PTSD may reflect prior trauma exposure, especially early in life. Early life, including the prenatal period, is a critical time in rodents, and may well be for humans, for the functional and structural development of the immune and nervous systems. These, in turn, are likely shaped and programmed by gut and possibly other bacteria. Recent experimental and clinical data converge on the hypothesis that imbalanced gut microbiota in early life may have long-lasting immune and other physiologic effects that make individuals more susceptible to develop PTSD after a traumatic event and contribute to the disorder. This suggests that it may be possible to target abnormalities in these systems by manipulation of certain gut bacterial communities directly through supplementation or indirectly by dietary and other novel approaches. PMID- 27254414 TI - Clinically Significant Differences among Canadian Mental Health Acts: 2016. PMID- 27254413 TI - Reframing the Teenage Wasteland: Adolescent Microbiota-Gut-Brain Axis. AB - Human adolescence is arguably one of the most challenging periods of development. The young adult is exposed to a variety of stressors and environmental stimuli on a backdrop of significant physiological change and development, which is especially apparent in the brain. It is therefore unsurprising that many psychiatric disorders are first observable during this time. The human intestine is inhabited by trillions of microorganisms, and evidence from both preclinical and clinical research focusing on the established microbiota-gut-brain axis suggests that the etiology and pathophysiology of psychiatric disorders may be influenced by intestinal dysbiosis. Provocatively, many if not all of the challenges faced by the developing teen have a documented impact on these intestinal commensal microbiota. In this review, we briefly summarize what is known about the developing adolescent brain and intestinal microbiota, discuss recent research investigating the microbiota-gut-brain axis during puberty, and propose that pre- and probiotics may prove useful in both the prevention and treatment of psychiatric disorders specifically benefitting the young adult. PMID- 27254415 TI - Characterization of Disability in Canadians with Mental Disorders Using an Abbreviated Version of a DSM-5 Emerging Measure: The 12-Item WHO Disability Assessment Schedule (WHODAS) 2.0. AB - OBJECTIVE: The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) is a disability scale included in Section 3 of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a possible replacement for the Global Assessment of Functioning Scale (GAF). To assist Canadian psychiatrists with interpretation of the scale, we have conducted a descriptive analysis using data from the 2012 Canadian Community Health Survey Mental Health component (CCHS-MH). METHODS: The 2012 CCHS-MH was a cross sectional survey of the Canadian community (n = 23,757). The survey included an abbreviated 12-item version of the WHODAS 2.0. Mental disorder diagnoses were assessed for schizophrenia, other psychosis, major depressive episode (MDE), generalized anxiety disorder (GAD), bipolar I disorder, substance abuse/dependence, and alcohol abuse/dependence. RESULTS: Mean scores ranged from 14.2 (95% CI, 14.1 to 14.3) for the overall community population to 23.1 (95% CI, 19.5 to 26.7) for those with schizophrenia, with higher scores indicating greater disability. Furthermore, the difference in scores between those with lifetime and past-month episodes suggests that the scale is sensitive to changes occurring during the course of these disorders; for example, scores varied from 23.6 (95% CI, 22.2 to 25.1) for past-month MDE to 14.4 (95% CI, 14.2 to 14.7) in the lifetime MDE group without a past-year episode. CONCLUSION: This analysis suggests that the WHODAS 2.0 may be a suitable replacement for the GAF. As a disability measure, even though it is not a mental health-specific instrument, the 12-item WHODAS 2.0 appears to be sensitive to the impact of mental disorders and to changes over the time course of a mental disorder. However, the clinical utility of this measure requires additional assessment. PMID- 27254417 TI - The Association of Level of Internet Use with Suicidal Ideation and Suicide Attempts in South Korean Adolescents: A Focus on Family Structure and Household Economic Status. AB - OBJECTIVE: To examine the association between the level of Internet addiction and suicidal ideation and suicide attempts in South Korean adolescents, focusing on the roles of family structure and household economic status. METHODS: Data from 221 265 middle and high school students taken from the 2008-2010 Korea Youth Risk Behavior Web-based Survey were used in this study. To identify factors associated with suicidal ideation/attempts, multiple logistic regression analysis was performed. The level of Internet use was measured using the simplified Korean Internet Addiction Self-assessment Tool. RESULTS: Compared with mild users of the Internet, high-risk users and potential-risk users were more likely to report suicidal ideation (nonuser, odds ratio [OR] 1.10, 95% confidence interval [CI] 1.05 to 1.15; potential risk, OR 1.49, 95% CI: 1.36 to 1.63; high risk OR 1.94, 95% CI 1.79 to 2.10) or attempts (nonuser, OR 1.33, 95% CI 1.25 to 1.42; potential risk, OR 1.20, 95% CI 1.04 to 1.38; high risk, OR 1.91, 95% CI 1.71 to 2.14). The nonuser group also had a slightly higher risk of suicidal ideation/attempts compared with mild users. This association appeared to vary by perceived economic status and family structure. CONCLUSIONS: Our study suggests that it is important to attend to adolescents who are at high risk for Internet addiction, especially when they do not have parents, have stepparents, or perceive their economic status as either very low or very high. PMID- 27254416 TI - Validation of the French Version of Conners' Parent Rating Scale Revised, Short Version: Factorial Structure and Reliability. AB - OBJECTIVE: Attention-deficit hyperactivity disorder is one of the most frequent neurodevelopmental disorders. Its diagnosis requires reference questionnaires such as the Conners' Parent Rating Scale (CPRS). Presently, in French-speaking countries, a few translations of the revised short CPRS have been put to use without previous formal validation. We sought here for the validation of a French version (Lausanne, Switzerland) of the revised short CPRS regarding construct validity, internal consistency, and item reliability in a sample of French schoolchildren. METHOD: The study involved 795 children and adolescents aged 9 to 19 years from a single school. The factorial structure and item reliability were assessed with a confirmatory factor analysis for ordered categorical variables. The dimension internal consistency was assessed with Guttman's lambda 6 coefficient. RESULTS: The results confirmed the original and strong 3-dimensional factorial structure (Oppositional, Cognitive Problems/Inattention, and Hyperactivity), showed satisfactory item reliability, and indicated a good dimension internal consistency (Guttman's lambda 6 coefficient: 0.87, 0.90, and 0.82, respectively, to the 3 dimensions). CONCLUSIONS: Thus, the Lausanne French version of the revised short CPRS may be considered validated regarding construct validity and item and dimension reliability; it can be now more confidently used in clinical practice. PMID- 27254419 TI - Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells. AB - The anticancer effects of fisetin, a dietary agent, are largely unknown against human gastric cancer. Herein, we investigated the mechanisms of fisetin-induced inhibition of growth and survival of human gastric carcinoma AGS and SNU-1 cells. Fisetin (25-100 MUM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells. We also observed that growth suppression and death of non neoplastic human intestinal FHs74int cells were minimally affected by fisetin. Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells. DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP. Fisetin-induced apoptosis was observed to be independent of p53. DCFDA and MitoSOX analyses showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion. It also increased cellular nitrite and superoxide generation. Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin induced DNA damage. The formation of comets were observed in only fisetin treated cells which was blocked by NAC pre-treatment. Further investigation of the source of ROS, using mitochondrial respiratory chain (MRC) complex inhibitors, suggested that fisetin caused ROS generation specifically through complex I. Collectively, these results for the first time demonstrated that fisetin possesses anticancer potential through ROS production most likely via MRC complex I leading to apoptosis in human gastric carcinoma cells. (c) 2016 Wiley Periodicals, Inc. PMID- 27254422 TI - A flying start. AB - The A&E Department at Warrington is a busy one, dealing with 70,000 new attenders per year with major trauma accounting for up to 2 per cent of these ( 1 ). Accordingly, trauma management has a high profile. PMID- 27254420 TI - The Longitudinal Effect of Emotion Regulation Strategies on Anxiety Levels in Children and Adolescents. AB - : There is growing evidence linking emotion dysregulation to anxiety. However, few studies have examined this relationship longitudinally or developmentally. Additionally, no studies have specifically examined the predictive relevance of the emotion regulation skills taught in mindfulness- and acceptance-based therapies. We explore whether specific emotion regulation processes differentially predict specific anxiety symptoms over time among children and adolescents. METHODS: Initial emotion non-awareness, nonacceptance, and difficulties with goal-directed behavior were assessed in a community sample (n = 312, age range = 8-16, mean age = 11.68, 59% female, 69% Caucasian). Social anxiety, separation anxiety, and physical anxiety symptoms were assessed every 3 months for 3 years. Hierarchical linear modeling was used to examine the concurrent and longitudinal effects of emotion dysregulation assessed at baseline or 18 months on anxiety. RESULTS: After controlling for depression, age, and gender, all three processes concurrently predicted physical and social anxiety, and all but nonacceptance predicted separation anxiety. Only difficulties with goal-directed behavior, however, predicted longitudinal change in separation anxiety over time with covariates. Additionally, emotion non-awareness and difficulties with goal-directed behavior predicted subsequent changes in social anxiety. CONCLUSIONS: Emotion dysregulation may serve as a potential risk factor for the development of anxiety symptoms among youth. It may be beneficial to target reductions in maladaptive strategies in prevention or intervention work. PMID- 27254423 TI - Environmental provisions for children in A&E. AB - The need to consider the effect of the hospital environment on the hospitalised child has been well established for over 30 years ( 1 ). While this has led to a more cheerful and appealing environment on paediatric wards, similar changes have not been reflected in AE departments ( 2 ), despite the fact that about three million children attend AE throughout the UK each year ( 3 ). PMID- 27254421 TI - Clinical features and treatment outcomes of peripheral T-cell lymphoma in children. A current data report from Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). AB - PURPOSE: Peripheral T-cell lymphomas (PTCL) are lymphoproliferative disorders derived from post-thymic cells, that occur extremely rarely in children. The optimal treatment of pediatric PTCL remains still unclear. PATIENTS AND METHODS: Ten children with PTCL from 3 up to 18 years of age registered by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) were retrospectively analyzed. All patients were treated with different regimens including protocols: for lymphoblastic lymphoma in 7 cases, for anaplastic large cell lymphoma in 1, CHOP in 1. Five of the 10 patients with PTCL were classified as stage II; 4 as stage III and 1 as stage IV due to extralymphatic organs (bone marrow) involvement. Four histological subtypes of PTCL were recognized: extranodal NK/T-cell lymphoma, nasal type (ENTNT), peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), subcutaneous panniculitis-like T-cell lymphoma (SPL), Sezary syndrome (SS). After first-line therapy 9 patients initially achieved complete remission, 4 relapsed, 5 died. One patient achieved remission spontaneously. Three children (1 with stage IV and 2 in relapse) underwent high-dose chemotherapy with allogeneic bone marrow stem cell transplantation and all of them are alive and in CR. RESULTS: The cumulative probability of 5-year overall survival (OS) for our whole group was 63.9% (95%CI: 35.2-88.2%) with a median follow-up time of 48.4 months (range 24-90+ months). The 5-year event free survival (EFS) was 81%. PTCLs are a heterogeneous and rare group of childhood NHLs. CONCLUSIONS: According to our experience the standard chemotherapy for precursor lymphomas seems to be a beneficial treatment option for children with PTCL. Allogeneic stem cell transplantation may improve the outcome in selected patients. PMID- 27254424 TI - Blood transfusions. PMID- 27254425 TI - Stabbing injuries. AB - Low velocity penetrating injuries commonly occur in the younger adult male. In a study of 80, 20-39 year olds in a Teeside hospital, 71 cases of penetrating injuries involved males. Within this group, four categories emerged; 20 stabbing injuries, four traumatic amputations and three gunshot wounds ( 1 ). From these figures it is necessary to clarify the meaning of the terms laceration and stabbing. 'Hie former is a tear to the flesh causing disruption of the skin structure, the latter is classified as a low velocity penetrating injury in which trauma is caused by a single blade, but may be multiple. This is compared with medium and high energy trauma associated with firearms, where tumble and fragmentation of bullets lead to secondary tissue trauma ( 2 ). PMID- 27254426 TI - Methods: pain. AB - Pain is one of the most common reasons for patient attendance at A&E departments ( 1 ), and its management should be a high priority in patient care. In order to do this, an assessment of pain is vital in determining the patient's progress, the impact and efficacy of treatment, and in some cases, as a diagnostic tool ( 2 ). PMID- 27254427 TI - Provision of clean injecting equipment. AB - Providing clean needles and syringes to injecting drug users is one established strategy to prevent the spread of HIV and other blood borne infections ( 1 ). Our A&E department had been faced with problems from intravenous (IV) drug users requesting clean injecting equipment, and we wanted to know how other A&Es dealt with such requests, and whether they experienced similar problems. PMID- 27254428 TI - Burns trauma: management and nursing care Chrissie Bosworth Bailliere Tindall 220pp L19.95 1-873853-32-7 1873853327. AB - The management and nursing care of burn trauma is a specialised area that requires a wealth of knowledge and clinical skills from the members of a large multidisciplinary team. PMID- 27254430 TI - New this month. AB - Critical Care Nursing: Science &Practice Sheila Adam and Sue Osborne Oxford Medical Publications 445pp ISBN a 19-263022-9. PMID- 27254431 TI - The Royal Marsden NHS Trust manual of clinical nursing procedures (fourth edition) The Royal Marsden NHS Trust manual of clinical nursing procedures (fourth edition) Jane Mallett and Christopher Bailey (Editors) Blackwell Science 662pp L15.99 0632-04068-8 0632040688. AB - Those who are familiar with earlier editions of this book will understand why it has become the definitive manual of clinical nursing procedures. It is because of its high quality, and common-sense approach, combined with a rigorous attention to detail. PMID- 27254432 TI - Abuse, Neglect and Exploitation of Older Persons: Strategies for Assessment and Intervention Abuse, Neglect and Exploitation of Older Persons: Strategies for Assessment and Intervention Lorin Baumhover and S Colleen Beall Jessica Kingsley publishers 269pp L18.95 1-85302-405-8 1853024058. AB - The abuse of older people is an emotive issue and has been a focus for policy makers for some time now. This text, however, deals with issues of neglect and exploitation in detail, giving valuable guidance and sources of reference for care staff. 'Hie characteristics and recognition of all types of abuse are thoroughly explained, as well as the formal assessment process and documentation required. It then follows thera peufic intervention and effective discharge planning, culminating in an abuse prevention programme for staff working in long term- care. The training material is useful for all levels of staff. PMID- 27254433 TI - Paracetamol overdoses Paracetamol overdoses Fagan E Wannan G Reducing paracetamol overdoses. British Medical Journal . 1996 . 313 , 1417 - 1418 . AB - Medicines containing paracetamol are the most common cause of intentional drug overdose in Britain with about 70,000 cases of paracetamol overdose each year. Fortunately, death from overdose is fare - about 200 cases - Against a safety record of 30 million packs containing paracetamol sold each year. PMID- 27254434 TI - Air gun dangers. AB - The handgun debate in the UK has heard arguments about the use of air guns, which assumes small lead pellets have a limited tissue penetration and do not cause significant tissue damage unless a vital structure is directly hit. A study of air gun injuries in paediatric patients treated at the University of Louisville contradicts this belief. PMID- 27254436 TI - Heparin plus aspirin for unstable angina. AB - Adding heparin to aspirin in the treatment of people with unstable angina reduces the risk of myocardial infarction or death, research suggests. A meta-analysis was undertaken of six randomised trials which compared aspirin alone with aspirin plus heparin. The overall summary relative risk of myocardial infarction or death during randomised treatment was 0.67 in those treated with aspirin plus heparin compared with those treated with heparin alone. The risk for recurrent ischaemic pain was 0.68, 0.82 for infarction or death two to 12 weeks post-randomisation, 1.03 for revascularisation and 1.99 for major bleeding. PMID- 27254435 TI - Teenager's risk taking behaviour. AB - Adolescents who use unhealthy methods to lose weight fire likely to engage in other unhealthy behaviours, researcher say. PMID- 27254438 TI - Information wanted. PMID- 27254439 TI - Childhood accidents. PMID- 27254440 TI - Evaluation of the efficiency under current use of human fibrinogen concentrate in trauma patients with life-threatening hemorrhagic disorders. AB - The aim of the study was to assess the influence of fibrinogen concentrate on survival when it is used in trauma patients with life-threatening hemorrhagic disorders. Secondly, to evaluate when the fibrinogen concentrate administration maximizes its efficacy, and to describe what other concomitant treatment the patients received in order to control their life-threatening hemorrhage. Retrospective, observational, and multicenter study was carried out in three trauma areas between June 2012 and June 2014. The totality of trauma patients with a documented life-threatening hemorrhage who received a fibrinogen concentrate prescription was included in the study. Demographic and analytical data, admission diagnosis, treatment indication, fibrinogen concentrate dose, survival after 1 and 7 days, hospitalization time, and concomitant blood product treatment were collected. One hundred and twenty-three patients were finally included. The mean dose of fibrinogen concentrate administered was 2.87 g. The mean initial fibrinogen plasma level was 1.49 g/l, which rose to 2.26 g/l. The number of patients who survived after 24 h was 80.49%, and 69.11% after 7 days. Lower fibrinogen plasma levels are statistically associated with a higher probability of death after 7 days (P = 0.004). The most suitable threshold to recommend the fibrinogen concentrate administration has been found to be 1.5 g/dl (P = 0006, after 24 h; P = 0.032, after 7 days). Finally, the most common concomitant treatment was the erythrocytes concentrate. A statistically significant relationship between lower fibrinogen plasma levels and a higher probability of death after 7 days has been found. Our data support the threshold of 1.5 g/l as the recommended level to administer fibrinogen concentrate in trauma patients. PMID- 27254441 TI - Coagulation abnormalities identified by thromboelastometry in patients with severe sepsis: the relationship to endotoxemia and mortality. AB - The aim of this study was to monitor the development of coagulation abnormalities in patients with severe sepsis using thromboelastometry and to assess whether increased endotoxin activity was associated with a change in coagulation. Data collected on ICU admission, day 2, 3, and 4 were analysed in 61 patients. Thromboelastometry made it possible to identify patients with a normal (group 1), hypercoagulable (group 2), or hypocoagulable (group 3) pattern. The best accuracy of thromboelastometry parameters as potential indices of coagulation abnormalities was yielded by the clot formation time and maximum clot firmness. The mortality rate was low in group 1(16%) and the presence of abnormalities, indicating either a hyper or hypocoagulation pattern, was associated with significantly higher mortality (42 and 39% respectively; P = 0.05). In group 1, baseline endotoxin activity was low [0.22 endotoxin activity units (EAU), 0.15 0.43] and did not change significantly during the observation period. In group 2, baseline endotoxin activity was elevated (0.52 EAU (0.39-0.62)) and remained high on day 2, 3, and 4. In group 3, baseline endotoxin activity was elevated (0.56 EAU (0.28-0.80)) and similarly to group 2, remained high on day 2, 3, and 4. The presence of coagulation disorders indicates a high-risk subpopulation of critically ill patients as reflected in significantly higher mortality rates and increased endotoxin activity. PMID- 27254442 TI - The value and impact of anti-Xa activity monitoring for prophylactic dose adjustment of low-molecular-weight heparin during pregnancy: a retrospective study. AB - : Low-molecular-weight heparin (LMWH) is the anticoagulant drug class of choice for the prevention of thrombosis during pregnancy and often used for prevention of severe obstetrical complications, yet the optimal dosage is still a matter of debate. Although several studies have evaluated LMWH dose adjustment methods based on anti-Xa levels, no definitive conclusion as yet exists. This extensive retrospective study sought to address the rationale of regular anti-Xa activity monitoring in pregnant patients given LMWH prophylaxis. We evaluated pregnant patients receiving LMWH prophylaxis with three or more anti-Xa measurements. The initial LMWH dose was fixed and adjusted for obesity. The desired anti-Xa activity was 0.2-0.6 IU/ml and LMWH dose was increased for anti-Xa levels less than 0.3 IU/ml. Of the 173 enrolled women, 79% required LMWH dose adjustment (56%: one dose increase; 20%: two; 3%: three). In the vast majority of patients, LMWH dose was increased before substantial body weight gain. The number of dose adjustments positively correlated with BMI, though not with body weight gain. Based on our study findings, we recommend conducting LMWH dose adjustments based on anti-Xa levels, monitored regularly during pregnancy to keep the anti-Xa activity within the desired range. PMID- 27254443 TI - Active inductor based fully integrated CMOS transmit/ receive switch for 2.4 GHz RF transceiver. AB - Modern Radio Frequency (RF) transceivers cannot be imagined without high performance (Transmit/Receive) T/R switch. Available T/R switches suffer mainly due to the lack of good trade-off among the performance parameters, where high isolation and low insertion loss are very essential. In this study, a T/R switch with high isolation and low insertion loss performance has been designed by using Silterra 0.13um CMOS process for 2.4GHz ISM band RF transceivers. Transistor aspect ratio optimization, proper gate bias resistance, resistive body floating and active inductor-based parallel resonance techniques have been implemented to achieve better trade-off. The proposed T/R switch exhibits 0.85dB insertion loss and 45.17dB isolation in both transmit and receive modes. Moreover, it shows very competitive values of power handling capability (P1dB) and linearity (IIP3) which are 11.35dBm and 19.60dBm, respectively. Due to avoiding bulky inductor and capacitor, the proposed active inductor-based T/R switch became highly compact occupying only 0.003mm2 of silicon space; which will further trim down the total cost of the transceiver. Therefore, the proposed active inductor-based T/R switch in 0.13um CMOS process will be highly useful for the electronic industries where low-power, high-performance and compactness of devices are the crucial concerns. PMID- 27254444 TI - Nematode larvae infecting Priacanthus arenatus Cuvier, 1829 (Pisces: Teleostei) in Brazil. AB - From July to December, 2013, thirty Priacanthus arenatus specimens commercialized in the cities of Niteroi and Rio de Janeiro, State of Rio de Janeiro, were acquired. The fish were necropsied and filleted to investigate the presence of nematode larvae. Twenty fish (66.7%) out of the total were parasitized by nematode larvae. A total of 2024 larvae were collected; among them, 30 third instar larvae of Anisakis sp. showed prevalence (P) = 20%, mean abundance (MA) = 1, and the mean intensity (MI) = 5, and infection sites (IS) = caecum, stomach, liver, and mesentery; and 1,994 third-instar larvae (1,757 encysted and 237 free) of Hysterothylacium deardorffoverstreetorum with P = 66.7%, MA = 66.5, and MI = 99.7, and IS = spleen, caecum, stomach, liver, mesentery, and abdominal muscle. This is the first study to report H. deardorffoverstreetorum and Anisakis sp. larvae parasitizing P. arenatus. PMID- 27254445 TI - In vitro antifungal activity of four chemotypes of Lippia alba (Verbenaceae) essential oils against Alternaria solani (Pleosporeaceae) isolates. AB - Several volatile natural compounds produced by plant secondary metabolism have been proven to present antimicrobial action, enabling their use in phytopathogen control. They also present low environmental impact when compared to conventional pesticides. Essential oils contain these compounds and can be found in several plant species, such as Lippia alba (Mill.) N.E. Brown (Verbenaceae). Essential oils of four chemotypes of L. alba, characterized by their major compounds, namely camphor, citral, linalool and camphor/1,8-cineole, were tested against the phytopathogen Alternaria solani Sorauer (Pleosporaceae), which causes early blight on tomatoes and is responsible for great economic losses regarding production. Essential oils antifungal action was tested in vitro using potato dextrose agar medium with essential oil concentrations at 0.1, 0.5, 1.0, 1.5 and 2.0 uL mL-1. The chemotype that had the best performance was citral, showing significant inhibition compared to the others, starting at the 0.5 uL mL-1 concentration. The essential oil belonging to the linalool chemotype was efficient starting at the 1.5 uL mL-1 concentration. Conversely, the camphor chemotype did not show any action against the phytopathogen. Moreover, the essential oils had no remarkable effect on tomato germination and growth. In conclusion, these essential oils presented fungicidal action against A. solani. PMID- 27254446 TI - Development of Dichelops melacanthus and its egg parasitoid Telenomus podisi reared on Bt-soybean MON 87701 x MON 89788 and its near conventional isoline under different temperatures. AB - Dichelops melacanthus was studied under controlled conditions (60 +/- 10% RH and 14/10 h L/D photoperiod), and three constant temperatures (19, 25, and 31 +/- 2 degrees C). Fresh pods of MON 87701 * MON 89788 soybeans and its near non-Bt isoline (A5547) were supplied to nymphs and adults. The biology of T. podisi was studied in the same controlled RH conditions, but only at the standard temperature of 25 +/- 2 degrees C. Overall, the development of D. melacanthus was better at higher temperatures, which accelerated the development of the stink bug without affecting adult biological parameters. No influence of Bt-soybeans on the biology of the pest was observed in any temperature studied, which shows that D. melacanthus is not affected by this transgenic soybean. The egg parasitoid T. podisi also was not harmed when it parasitized eggs of the pest fed with MON 87701 * MON 89788 soybeans, with similar results to those obtained in non-Bt isogenic soybeans. Thus, this study demonstrates that D. melacanthus is favored at high temperatures (31 +/- 2 degrees C), and that neither did MON 87701 * MON 89788 soybean pods affect the development of the pest nor its parasitoid T. podisi. PMID- 27254447 TI - Branching, flowering and fruiting of Jatropha curcas treated with ethephon or benzyladenine and gibberellins. AB - Jatropha curcas L. has been identified for biofuel production but it presents limited commercial yields due to limited branching and a lack of yield uniformity. The objective of this study was to evaluate the effects of single application of ethephon or a combination of 6-benzyladenine (BA) with gibberellic acid isomers A4 and A7 (GA4+7) on branch induction, flowering and fruit production in jatropha plants with and without leaves. Plants with and without leaves showed differences for growth and reproductive variables. For all variables except inflorescence set, there were no significant statistical interactions between the presence of leaves and plant growth regulators concentration. The total number of flowers per inflorescence was reduced as ethephon concentration was increased. As BA + GA4 +7 concentration increased, seed dry weight increased. Thus, ethephon and BA + GA4 +7 applications appeared to affect flowering and seed production to a greater extent than branching. The inability to discern significant treatment effects for most variables might have been due to the large variability within plant populations studied and thus resulting in an insufficient sample size. Therefore, data collected from this study were used for statistical estimations of sample sizes to provide a reference for future studies. PMID- 27254448 TI - Mesothelin as a biomarker for ovarian carcinoma: a meta-analysis. AB - The objective of this work was to estimate the accuracy of mesothelin as a biomarker for ovarian cancer. A quantitative systematic review was performed. A comprehensive search of the Medline, LILACS, SCOPUS, Embase, Cochrane Central Register of Controlled Trials, Biomed Central, and ISI Web of Science databases was conducted from January 1990 to June 2015. For inclusion in this systematic review, the papers must have measured mesothelin levels in at least two histological diagnoses; ovarian cancer (borderline or ovarian tumor) vs. benign or normal ovarian tissue. For each study, 2 x 2 contingency tables were constructed. We calculated the sensitivity, specificity and diagnostic odds ratio. The verification bias was performed according to QUADAS-2. Statistical analysis was performed with the software Stata 11, Meta-DiSc(r) and RevMan 5.2. Twelve studies were analyzed, which included 1,561 women. The pooled sensitivity was 0.62 (CI 95% 0.58 - 0.66) and specificity was 0.94 (CI 95% 0.92 - 0.95). The DOR was 38.92 (CI 95% 17.82 - 84.99). Our systematic review shows that mesothelin cannot serve alone as a biomarker for the detection of ovarian cancer. PMID- 27254449 TI - Metabolic responses of channel catfish (Ictalurus punctatus) exposed to phenol and post-exposure recovery. AB - Metabolic adjustments were studied in channel catfish Ictalurus punctatus exposed to 1.5 mg L-1 of phe nol (10% LC50) for four days and recovered for seven days. Lower triacylglycerol (TGA) stores and increased muscle fat free acids (FFA) suggest fat catabolism in muscle. Remarkable liver FFA decrease (-31%) suggests liver fat catabolism as well. Increased muscular ammonia levels and ASAT (aspartate aminotransferase) and decreased plasma aminoacids suggest higher muscular amino acid uptake. Constant levels of glucose and increased liver glycogen stores, associated with lower amino acids in plasma, indicate gluconeogenesis from amino acids. This is supported by higher hepatic ALAT and ASAT. Higher hepatic LDH followed by lower plasma lactate may indicate that plasma lactate was also used as gluconeogenic substrate. Biochemical alterations were exacerbated during the post-exposure recovery period. Reduction in muscle and plasma protein content indicate proteolysis. A higher rate of liver fat catabolism was resulted from a remarkable decrease in hepatic TGA (-58%). Catabolic preference for lipids was observed in order to supply such elevated energy demand. This study is the first insight about the metabolic profile of I. punctatus to cope with phenol plus its ability to recover, bringing attention to the biological consequences of environmental contamination. PMID- 27254450 TI - Trade-off between reservoir yield and evaporation losses as a function of lake morphology in semi-arid Brazil. AB - This study investigates the relationships between yield and evaporation as a function of lake morphology in semi-arid Brazil. First, a new methodology was proposed to classify the morphology of 40 reservoirs in the Ceara State, with storage capacities ranging from approximately 5 to 4500 hm3. Then, Monte Carlo simulations were conducted to study the effect of reservoir morphology (including real and simplified conical forms) on the water storage process at different reliability levels. The reservoirs were categorized as convex (60.0%), slightly convex (27.5%) or linear (12.5%). When the conical approximation was used instead of the real lake form, a trade-off occurred between reservoir yield and evaporation losses, with different trends for the convex, slightly convex and linear reservoirs. Using the conical approximation, the water yield prediction errors reached approximately 5% of the mean annual inflow, which is negligible for large reservoirs. However, for smaller reservoirs, this error became important. Therefore, this paper presents a new procedure for correcting the yield-evaporation relationships that were obtained by assuming a conical approximation rather than the real reservoir morphology. The combination of this correction with the Regulation Triangle Diagram is useful for rapidly and objectively predicting reservoir yield and evaporation losses in semi-arid environments. PMID- 27254451 TI - Probiotic level effects on growth performance, carcass traits, blood parameters, cecal microbiota, and immune response of broilers. AB - Probiotic effects on growth performance, carcass traits, blood parameters, cecal microbiota, and immune response of broilers were studied. Two hundred one-day-old male chickens were allocated to one of five treatments (four replicates of 10 birds per treatment): control, and the same control diet supplemented with 0.005%, 0.01%, 0.015% and 0.02% probiotics. Probiotics in feed at 0.01% or higher levels of supplementation improved body weight gain (+12%) and feed conversion rate (-5%) compared with the control. There were no effects on carcass traits, but the relative weights of drumsticks and wings showed increasing and decreasing linear responses, respectively, to probiotic supplementation level. Blood plasma glucose and albumin contents linearly increased (from 167.1 to 200.5 mg dl-1, and from 1.70 to 3.25 g dl-1) with increasing probiotic supplementation. Triglycerides and cholesterol contents were lower in probiotic supplemented treatments (average contents 71.3 and 125.3 mg dl-1 vs. 92.6 and 149.9 mg dl-1 in the control). Probiotics decreased cecal Escherichia coli counts, but had no effects on immunity related organs or immune response. The linear trends, either positive or negative, observed in many of the parameters studied, suggest that more studies are needed to establish the optimal concentration of probiotics in broiler feed. PMID- 27254452 TI - Bovine meat and bone meal is an economically viable alternative in quail feeding in the initial phase. AB - Quail egg production has experienced a steep rise in the last decade. Nutrition is the main factor affecting productive potential in the poultry industry, as appropriate nutritional management is necessary to ensure the maintenance of optimal physical conditions, growth and the production of high quality products. Meat and bone meal (MBM) has often been used in the poultry industry as an alternative and cost-effective source of protein in partial replacement of corn and soybean meal. However, there have been no studies to date that have investigated the effect of dietary MBM on the performance of quail or on the costs of production in the starter phase. This is particularly important considering that this phase is characterized by large investments by producers, without immediate economic return. In this study, we investigated whether partial replacement of soybean meal (SBM) by meat and bone meal (MBM) in the diet of Japanese quail during the starter phase is a viable alternative that would maintain or improve their productive and economic performance. Our results show that the inclusion of MBM in the diet of quail reduces feeding costs by up to 6% without impairing productive performance. PMID- 27254453 TI - Assessment and kinetics of soil phosphatase in Brazilian Savanna systems. AB - The activity and kinetics of soil phosphatases are important indicators to evaluate soil quality in specific sites such as the Cerrado (Brazilian Savanna). This study aimed to determine the activity and kinetic parameters of soil phosphatase in Cerrado systems. Soil phosphatase activity was assessed in samples of native Cerrado (NC), no-tillage (NT), conventional tillage (CT) and pasture with Brachiaria brizantha (PBb) and evaluated with acetate buffer (AB), tris-HCl buffer (TB), modified universal buffer (MUB) and low MUB. The Michaelis-Menten equation and Eadie-Hofstee model were applied to obtain the kinetic parameters of soil phosphatase using different concentrations of p-nitrophenol phosphate (p NPP). MUB showed the lowest soil phosphatase activity in all soils whereas AB in NC and NT presented the highest. Low MUB decreased interferences in the assessment of soil phosphatase activity when compared to MUB, suggesting that organic acids interfere on the soil phosphatase activity. In NC and NT, soil phosphatase activity performed with TB was similar to AB and low MUB. Km values from the Michaels-Menten equation were higher in NC than in NT, which indicate a lower affinity of phosphatase activity for the substrate in NC. Vmax values were also higher in NC than in NT. The Eadie-Hofstee model suggests that NC had more phosphatase isoforms than NT. The study showed that buffer type is of fundamental importance when assessing soil phosphatase activity in Cerrado soils. PMID- 27254454 TI - Interconnection between microstructure and microhardness of directionally solidified binary Al-6wt.%Cu and multicomponent Al-6wt.%Cu-8wt.%Si alloys. AB - An experimental study has been carried out to evaluate the microstructural and microhardness evolution on the directionally solidified binary Al-Cu and multicomponent Al-Cu-Si alloys and the influence of Si alloying. For this purpose specimens of Al-6wt.%Cu and Al-6wt.%Cu-8wt.%Si alloys were prepared and directionally solidified under transient conditions of heat extraction. A water cooled horizontal directional solidification device was applied. A comprehensive characterization is performed including experimental dendrite tip growth rates (VL) and cooling rates (TR) by measuring Vickers microhardness (HV), optical microscopy and scanning electron microscopy with microanalysis performed by energy dispersive spectrometry (SEM-EDS). The results show, for both studied alloys, the increasing of TR and VL reduced the primary dendrite arm spacing (l1) increasing the microhardness. Furthermore, the incorporation of Si in Al-6wt.%Cu alloy to form the Al-6wt.%Cu-8wt.%Si alloy influenced significantly the microstructure and consequently the microhardness but did not affect the primary dendritic growth law. An analysis on the formation of the columnar to equiaxed transition (CET) is also performed and the results show that the occurrence of CET is not sharp, i.e., the CET in both cases occurs in a zone rather than in a parallel plane to the chill wall, where both columnar and equiaxed grains are be able to exist. PMID- 27254455 TI - Influence of Duroc breed inclusion into Polish Landrace maternal line on pork meat quality traits. AB - Crossbreeding with Duroc breed allows to improve meat quality, but no data is available regarding specific influence of Duroc breed on characteristics of meat in the case of crossbreeding with various breeds. The aim of the present research was to evaluate the effect of crossbreeding Polish Landrace dames with Duroc sires on quality features of meat in reference to Polish Landrace breed. The objects of the study were Longissimus dorsi lumborum pork muscles obtained from Polish Landrace breed and Polish Landrace x Duroc crossbreed animals. Sarcomere length measurements were conducted using microscopic method and basic chemical composition measurement was analyzed using spectrophotometric scanning. Texture analysis of meat samples, performed after thermal treatment was expressed by Warner-Bratzler shear force and color analysis was obtained using CIE L*a*b* color system. No differences in sarcomere length, shear force as well as components of color values between pork meat originated from Polish Landrace breed and Polish Landrace x Duroc crossbreed were observed. Analysis of basic chemical composition revealed higher fat and lower ash contents in the case of meat of Polish Landrace breed animals. It was concluded that the actual impact of breed on meat characteristics is possibly altered by other factors. It may be suggested that influence of basic chemical composition on color of meat is breed related. PMID- 27254456 TI - Mercury bioaccumulation and isotopic relation between Trichiurus lepturus (Teleostei) and its preferred prey in coastal waters of southeastern Brazil. AB - The trophic transfer of total mercury (THg) and its bioaccumulation from prey species to the predator fish Trichiurus lepturus was analysed in coastal waters of southeastern Brazil to evaluate the trace element dynamic in this predator prey system. The isotopic (delta13C and delta15N) relation between this predator and its prey allowed inferences on prey assimilation and predator feeding habits. The THg increment varied from 4.5 to 19.5 times between prey and predator, with a biomagnification power of 0.59. The prey species could be divided into three groups regarding delta15N values: i) 13.6 to 13.20/00 (juvenile conspecifics, Pellona harroweri, and Peprilus paru); ii) 12.5 to 11.80/00 (Chirocentrodon bleekerianus, Lycengraulis grossidens, and Dorytheuthis plei); and iii) 10.50/00 (Xiphopenaeus kroyeri). Based on delta13C values, the prey groups were: i) 15.30/00 (X. kroyeri); ii) -17.6 to -16.80/00 (C. bleekerianus, D. plei, P. harroweri, P. paru, and juvenile conspecifics); and iii) -18.70/00 (L. grossidens). The values of THg and delta15N highlighted juvenile conspecifics as the main via of this trace element and the most assimilated prey. The isotopic relation between predator and its prey species showed a feeding activity preferably coastal and pelagic. PMID- 27254457 TI - Physiological behavior of bean's seeds and grains during storage. AB - Beans are one of the most used foods to meet the energy needs of the Brazilian diet, requiring farmers to use high seed physiological potential. The aim was to evaluate the physiological quality of beans stored for 360 days. Analyses were performed at 0, 30, 90, 180, 270, and 360 days after receiving the seeds (S1 and S2) and grains (G1 and G2) of BRS Splendor. Tests of germination, accelerated aging, cold, speed of germination, average length of shoots, and root were performed. The experimental design was completely randomized split-plot in time and the means were compared through Tukey test at 5% probability. Seed germination was not affected in S2, while the drop in S1 and G1 was significant. The vigor of grains from field 1 declined from 91 to 50% and from 93% to 76% by accelerated aging and cold, respectively, after 360 days. The germination speed tests performed showed a decreased during the experiment. The grains from field 1 had lower physiological quality. The accelerated aging and cold tests, through the speed of germination parameter, showed decrease in the vigor of the Splendor BRS. The storage period influenced the physiological quality of the beans tested. PMID- 27254458 TI - Antioxidant activity of oils extracted from orange (Citrus sinensis) seeds. AB - Due to the increasing production of food in the world with consequent increase of the production of waste, the importance of developing researches for its use is noticed. Thus, the interest in vegetable oils with bioactive compounds, such as the ones extracted from fruit seeds, is growing. Therefore, the present study aims to characterize the oils extracted from seeds of Hamlin, Natal, Pera-rio and Valencia orange varieties (Citrus sinensis), as to the levels of total carotenoids, total phenolic compounds, tocopherols and phytosterols, as well as to determine their antioxidant activity. The orange seed oils presented important content of total carotenoids (19.01 mg/kg), total phenolic compounds (4.43 g/kg), alpha-tocopherol (135.65 mg/kg) and phytosterols (1304.2 mg/kg). The antioxidant activity ranged from 56.0% (Natal) to 70.2% (Pera-rio). According to the results it is possible to conclude that the orange seed oils can be used as specialty oils in diet, since they contain considerable amounts of bioactive compounds and antioxidants. PMID- 27254459 TI - Electrochemically Produced Graphene for Microporous Layers in Fuel Cells. AB - The microporous layer (MPL) is a key cathodic component in proton exchange membrane fuel cells owing to its beneficial influence on two-phase mass transfer. However, its performance is highly dependent on material properties such as morphology, porous structure, and electrical resistance. To improve water management and performance, electrochemically exfoliated graphene (EGN) microsheets are considered as an alternative to the conventional carbon black (CB) MPLs. The EGN-based MPLs decrease the kinetic overpotential and the Ohmic potential loss, whereas the addition of CB to form a composite EGN+CB MPL improves the mass-transport limiting current density drastically. This is reflected by increases of approximately 30 and 70 % in peak power densities at 100 % relative humidity (RH) compared with those for CB- and EGN-only MPLs, respectively. The composite EGN+CB MPL also retains the superior performance at a cathode RH of 20 %, whereas the CB MPL shows significant performance loss. PMID- 27254460 TI - Peptide-Catalyzed Stereoselective Conjugate Addition Reactions of Aldehydes to Maleimide. AB - The tripeptide H-dPro-Pro-Asn-NH2 is presented as a catalyst for asymmetric conjugate addition reactions of aldehydes to maleimide. The peptidic catalyst promotes the reaction between various aldehydes and unprotected maleimide with high stereoselectivities and yields. The obtained products were readily derivatized to the corresponding pyrrolidines, lactams, lactones, and peptide like compounds. (1) H NMR spectroscopic, crystallographic, and computational investigations provided insight into the conformational properties of H-dPro-Pro Asn-NH2 and revealed the importance of hydrogen bonding between the peptide and maleimide for catalyzing the stereoselective C-C bond formation. PMID- 27254461 TI - A method for detergent-free isolation of membrane proteins in their local lipid environment. AB - Despite the great importance of membrane proteins, structural and functional studies of these proteins present major challenges. A significant hurdle is the extraction of the functional protein from its natural lipid membrane. Traditionally achieved with detergents, purification procedures can be costly and time consuming. A critical flaw with detergent approaches is the removal of the protein from the native lipid environment required to maintain functionally stable protein. This protocol describes the preparation of styrene maleic acid (SMA) co-polymer to extract membrane proteins from prokaryotic and eukaryotic expression systems. Successful isolation of membrane proteins into SMA lipid particles (SMALPs) allows the proteins to remain with native lipid, surrounded by SMA. We detail procedures for obtaining 25 g of SMA (4 d); explain the preparation of protein-containing SMALPs using membranes isolated from Escherichia coli (2 d) and control protein-free SMALPS using E. coli polar lipid extract (1-2 h); investigate SMALP protein purity by SDS-PAGE analysis and estimate protein concentration (4 h); and detail biophysical methods such as circular dichroism (CD) spectroscopy and sedimentation velocity analytical ultracentrifugation (svAUC) to undertake initial structural studies to characterize SMALPs (~2 d). Together, these methods provide a practical tool kit for those wanting to use SMALPs to study membrane proteins. PMID- 27254462 TI - Orthotopic mouse liver transplantation to study liver biology and allograft tolerance. AB - Orthotopic liver transplantation in the mouse is a powerful research tool that has led to important mechanistic insights into the regulation of hepatic injury, liver immunopathology, and transplant tolerance. However, it is a technically demanding surgical procedure. Setup of the orthotopic liver transplantation model comprises three main stages: surgery on the donor mouse; back-table preparation of the liver graft; and transplant of the liver into the recipient mouse. In this protocol, we describe our procedure in stepwise detail to allow efficient completion of both the donor and recipient operations. The protocol can result in consistently high technical success rates when performed by personnel experienced in the protocol. The technique can be completed in ~2-3 h when performed by an individual who is well practiced in performing mouse transplantation in accordance with this protocol. We have achieved a perioperative survival rate close to 100%. PMID- 27254464 TI - Adsorption and conformational modification of fibronectin and fibrinogen adsorbed on hydroxyapatite. A QCM-D study. AB - Hydroxyapatite is a bioactive ceramic frequently used for bone engineering/replacement. One of the parameters that influence the biological response to implanted materials is the conformation of the first adsorbed protein layer. In this work, the adsorption and conformational changes of two fibroid serum proteins; fibronectin and fibrinogen adsorbed onto four different hydroxyapatite powders are studied with a Quartz Crystal Microbalance with Dissipation (QCM-D). Each of the calcined apatites adsorbs less protein than their corresponding synthesized samples. Adsorption on synthesized samples yields always an extended conformation whereas a reorganization of the layer is observed for the calcined samples. Fg acquires a "Side on" conformation in all the samples at the beginning of the experiment except for one of the synthesized samples where an "End-on" conformation is obtained during the whole experiment. The Extended conformation is the active conformation for Fn. This conformation is favored by apatites with large specific surface area (SSA) and on highly concentrated media. Apatite surface features should be considered in the selection or design of materials for bone regeneration, since it is possible to control the conformation mode of attachment of Fn and Fg by an appropriate selection of them. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2585-2594, 2016. PMID- 27254463 TI - RecET direct cloning and Redalphabeta recombineering of biosynthetic gene clusters, large operons or single genes for heterologous expression. AB - Full-length RecE and RecT from Rac prophage mediate highly efficient linear linear homologous recombination that can be used to clone large DNA regions directly from genomic DNA into expression vectors, bypassing library construction and screening. Homologous recombination mediated by Redalphabeta from lambda phage has been widely used for recombinant DNA engineering. Here we present a protocol for direct cloning and engineering of biosynthetic gene clusters, large operons or single genes from genomic DNA using one Escherichia coli host that harbors both RecET and Redalphabeta systems. The pipeline uses standardized cassettes for horizontal gene transfer options, as well as vectors with different replication origins configured to minimize recombineering background through the use of selectively replicating templates or CcdB counterselection. These optimized reagents and protocols facilitate fast acquisition of transgenes from genomic DNA preparations, which are ready for heterologous expression within 1 week. PMID- 27254465 TI - Control of Polymer Phase Separation by Roughness Transfer Printing for 2D Microlens Arrays. AB - Great efforts have been devoted to the control of phase separation between blended polymers in terms of the advantages for engineering functional topologies. A simple and straightforward pathway through roughness transfer printing (RTP) is proposed to realize the control of polymer phase separation. The additional roughness difference, which is introduced by trace agarose transferred from a hydrogel stamp, offers a great effect on the rate of nucleation and coalescence orientation of polymethylmethacrylate (PMMA) protrusions grown from a polydimethylsiloxane (PDMS) network. Using a particular topography of agarose stamp and a proper growth time in toluene atmosphere, a 2D microlens array with high uniformity is obtained that shows great potential for optical applications. Moreover, the control of polymer phase separation was successfully extended to the collection and identification of fingerprints with a high degree of replication. PMID- 27254467 TI - Pyruvate Occupancy in the Carboxyl Transferase Domain of Pyruvate Carboxylase Facilitates Product Release from the Biotin Carboxylase Domain through an Intermolecular Mechanism. AB - Protein structure, ligand binding, and catalytic turnover contributes to the governance of catalytic events occurring at spatially distinct domains in multifunctional enzymes. Coordination of these catalytic events partially rests on the ability of spatially discrete active sites to communicate with other allosteric and active sites on the same polypeptide chain (intramolecular) or on different polypeptide chains (intermolecular) within the holoenzyme. Often, communication results in long-range effects on substrate binding or product release. For example, pyruvate binding to the carboxyl transferase (CT) domain of pyruvate carboxylase (PC) increases the rate of product release in the biotin carboxylase (BC) domain. In order to address how CT domain ligand occupancy is "sensed" by other domains, we generated functional, mixed hybrid tetramers using the E218A (inactive BC domain) and T882S (low pyruvate binding, low activity) mutant forms of PC. The apparent Ka pyruvate for the pyruvate-stimulated release of Pi catalyzed by the T882S:E218A[1:1] hybrid tetramer was comparable to the wild-type enzyme and nearly 10-fold lower than that for the T882S homotetramer. In addition, the ratio of the rates of oxaloacetate formation to Pi release for the WT:T882S[1:1] and E218A:T882S[1:1] hybrid tetramer-catalyzed reactions was 0.5 and 0.6, respectively, while the T882S homotetramer exhibited a near 1:1 coupling of the two domains, suggesting that the mechanisms coordinating catalytic events is more complicated that we initially assumed. The results presented here are consistent with an intermolecular communication mechanism, where pyruvate binding to the CT domain is "sensed" by domains on a different polypeptide chain within the tetramer. PMID- 27254468 TI - Graphitic Carbon Nanocubes Derived from ZIF-8 for Photothermal Therapy. AB - Graphitic carbon nanocubes (GCNCs) were prepared by pyrolysis of ZIF-8 nanocubes. The GCNCs resemble the structure of N-doped graphite and exhibit a high photothermal conversion efficiency of 40.4%. In vitro tests demonstrate that the GCNCs are highly biocompatible and induce an effective photothermal therapy effect under 808 nm irradiation. Our study provides a facile strategy for preparing functional carbon nanomaterials of prescribed size, morphology, and porous structure for bioapplications. PMID- 27254466 TI - Alcohol-Induced Developmental Origins of Adult-Onset Diseases. AB - Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID- 27254469 TI - Bone scaffolds loaded with siRNA-Semaphorin4d for the treatment of osteoporosis related bone defects. AB - Osteoporosis is a prominent disorder affecting over 200 million people worldwide. Recently, semaphorins have been implicated in the cell-cell communication between osteoclasts and osteoblasts and have been associated with the progression of osteoporosis. Previously, we demonstrated that knockdown of semaphorin4d (Sema4d) using siRNA delivered with a bone-targeting system prevented bone loss in an osteoporotic animal model. Here, we used this bone-specific technology containing siRNA-Sema4d and fabricated a PLLA scaffold capable of enhancing bone repair following fracture. We investigated the ability of the implant to release siRNA Sema4d into the surrounding tissues over time and to influence new bone formation in a 3 mm femur osteoporotic defect model in ovariectomized rats. Delivery of the bone-targeting system released from PLLA scaffolds began 2 hours post implantation, peaked at 1 day, and was sustained over a 21 day period. MUCT analysis demonstrated a significantly higher bone volume/total volume bone mineral density and number of osteoblasts in the rats that were transplanted with scaffolds loaded with siRNA-Sema4d. These results confirm the specific role of Sema4d in bone remodeling and demonstrate that significant increases in the speed and quality of new bone formation occur when siRNA-Sema4d is delivered via a PLLA scaffold. PMID- 27254471 TI - Two-wheel drive-based DNA nanomachine and its sensing potential for highly sensitive analysis of cancer-related gene. AB - With the biological significance and important advances of nano-scale DNA devices, scientific activities have been directed toward developing molecular machinery. In this work, we present a novel two-wheel drive-based DNA nanomachine composed of one signaling recognition probe (SRP), one label-free recognition probe (LRP), and one driving primer (DP). Target DNA hybridization can activate LRP-based wheel driving by resorting to DP-mediated polymerization/nicking/displacement cycles. This in turn results in the accumulation of nicked strand 1 (NS1) that can initiate extended SRP-based wheel driving. As a result, the hairpin structure of SRP is stretched and pre-quenched fluorescence is restored. Meanwhile, lots of nicked strand 2 (NS2) are produced, which could hybridize perfectly with SRP and lead to further fluorescence amplification. It is worth noting that, because the nanomachine operation relies strongly on inputted target trigger, the unwanted background is completely eliminated. The detection limit of 1 pM and an excellent capability to recognize the single-base mutation were achieved. Significantly, the interrogating of target trigger extracted from cancer cells is already available, reflecting the potential for practical applications. As a proof-of-concept building, the unique analytical properties would significantly benefit the DNA nanomachines and reveal great promise in biochemical and biomedical studies. PMID- 27254470 TI - Re-assessing the enhanced permeability and retention effect in peripheral arterial disease using radiolabeled long circulating nanoparticles. AB - As peripheral arterial disease (PAD) results in muscle ischemia and neovascularization, it has been claimed that nanoparticles can passively accumulate in ischemic tissues through the enhanced permeability and retention (EPR) effect. At this time, a quantitative evaluation of the passive targeting capabilities of nanoparticles has not been reported in PAD. Using a murine model of hindlimb ischemia, we quantitatively assessed the passive targeting capabilities of (64)Cu-labeled PEGylated reduced graphene oxide - iron oxide nanoparticles ((64)Cu-RGO-IONP-PEG) through the EPR effect using positron emission tomography (PET) imaging. Serial laser Doppler imaging was performed to monitor changes in blood perfusion upon surgical induction of ischemia. Nanoparticle accumulation was assessed at 3, 10, and 17 days post-surgery and found to be highest at 3 days post-surgery, with the ischemic hindlimb displaying an accumulation of 14.7 +/- 0.5% injected dose per gram (%ID/g). Accumulation of (64)Cu-RGO-IONP-PEG was lowest at 17 days post-surgery, with the ischemic hindlimb displaying only 5.1 +/- 0.5%ID/g. Furthermore, nanoparticle accumulation was confirmed by photoacoustic imaging (PA). The combination of PET and serial Doppler imaging showed that nanoparticle accumulation in the ischemic hindlimb negatively correlated with blood perfusion. Thus, we quantitatively confirmed that (64)Cu-RGO-IONP-PEG passively accumulated in ischemic tissue via the EPR effect, which is reduced as the perfusion normalizes. As (64)Cu-RGO-IONP-PEG displayed substantial accumulation in the ischemic tissue, this nanoparticle platform may function as a future theranostic agent, providing both imaging and therapeutic applications. PMID- 27254473 TI - Long-term outcomes following percutaneous hepatic vein recanalization for Budd Chiari syndrome. AB - BACKGROUND & AIMS: A proportion of patients with Budd-Chiari Syndrome (BCS) associated with stenosis or short occlusion of the hepatic vein (HV) or upper inferior vena cava (IVC) can be treated with recanalization by percutaneous venoplasty +/- HV stent insertion. We studied the long-term outcomes of this approach. METHODS: Single-centre retrospective analysis of patients referred for radiological assessment +/- intervention over a 27-year period. Of 155 BCS patients, 63 patients who underwent venoplasty were studied and compared to a previously reported series treated by TIPSS (n = 59). RESULTS: Patients treated with HV interventions (32 venoplasty alone, 31 endovascular stents): mean age, 34.9 +/- 10.9; M:F ratio 27:36; median follow-up, 113.0 months; 62% of patients had >=1 haematological risk factor. Technical success was 100%, with symptom resolution in 73%. Cumulative secondary patency at 1, 5, 10 years was 92%, 79%, 79% and 69%, 69%, 64% in the stenting and venoplasty groups respectively. Where long-term patency was not achieved, 10 patients required TIPSS, and 8 underwent surgery. Actuarial survival at 1, 5, 10 years was 97%, 89% and 85%. When compared to TIPSS, HV interventions resulted in similar patency and survival rates but significantly lower procedural complications (9.5% vs 27.1%) and hepatic encephalopathy (0% vs 18%). Patient age predicted survival following multivariate analysis. CONCLUSIONS: Our data support the stepwise approach to management of BCS, with very good outcomes from venoplasty combined with stenting when required. TIPSS should only be offered where HV interventions are not feasible or unsuccessful. PMID- 27254472 TI - Physiologic Frailty in Nonelderly Hematopoietic Cell Transplantation Patients: Results From the Bone Marrow Transplant Survivor Study. AB - Importance: Frailty results in decreased physiological reserve and diminished resistance to stressors; approximately 10% of those in the elderly population (those >=65 years) are frail. High-intensity treatments and complications after hematopoietic cell transplantation (HCT) injure normal tissues and may increase the risk of frailty even among nongeriatric HCT patients. Objective: To determine the prevalence of frailty in young adult HCT patients (18- to 64-year-olds) and siblings; and the impact of frailty on subsequent mortality in HCT survivors. Design, Setting, and Participants: This cohort study, conducted in August 2015 examined 998 HCT survivors, who underwent transplant procedures between 1974 and 1998, who have survived at least 2 years after HCT, and 297 frequency-matched siblings. The study was performed at City of Hope or University of Minnesota with participants completing surveys at home or in the clinic. Hematopoietic cell transplantation survivors and siblings participating in the Bone Marrow Transplant Survivor Study (BMTSS) completed a frailty survey between February 13, 1999 and June 15, 2005 (median time since HCT: 7.9 years); HCT survivors were followed for subsequent mortality (median: 10.3 years from survey). Main Outcomes and Measures: Prevalence and predictors of frailty; impact of frailty on subsequent mortality in HCT survivors. Frailty phenotype defined as exhibiting 3 or more of the following characteristics: clinically underweight, exhaustion, low energy expenditure, slow walking speed, and muscle weakness. The national Death Index, Social Security Death Index and medical records were used for mortality assessment as of December 21, 2011. Results: The 998 HCT survivors were a mean (SD) of 42.5 (11.6) years of age, and the 297 matched siblings were 43.8 (10.9) years of age. The prevalence of frailty among young adult HCT patients exceeded 8%. The HCT survivors were 8.4 times more likely to be frail than their siblings (95% CI, 2.0-34.5; P = .003). Among HCT recipients, allogeneic HCT recipients with chronic graft-vs-host disease (GvHD) were at increased risk of frailty compared with autologous HCT (OR,15.02; 95% CI, 6.6-34.3; P < .001); resolved chronic GvHD (OR, 2.7; 95% CI, 1.1-6.9; P = .04). Cumulative incidence of subsequent all-cause mortality was 39.3% and 14.7% at 10 years for HCT recipients with and without frailty, respectively (P < .001). Frailty was associated with a 2.76-fold (95% CI, 1.7-4.4; P < .001) increased risk of subsequent mortality after adjusting for relevant prognosticators. Conclusions and Relevance: The prevalence of frailty among young-adult HCT survivors approaches that seen in the elderly general population. Frail HCT survivors are at increased risk of subsequent mortality when compared with nonfrail survivors. This study identifies vulnerable populations needing close monitoring to anticipate and manage morbidity and prevent mortality. PMID- 27254474 TI - Exposure to Violence During Ferguson Protests: Mental Health Effects for Law Enforcement and Community Members. AB - There is little information available on the mental health effects of exposure to shared community violence such as the August 2014 violence that occurred in Ferguson, Missouri. This study sought to examine the relationship between proximity to community violence and mental health in both community members and police officers. We recruited 565 adults (community, n = 304, and police, n = 261) exposed to the violence in Ferguson to complete measures of proximity to violence, posttraumatic stress, depression, and anger. Using structural equation modeling, we assessed aspects of proximity to violence-connectedness, direct exposure, fear from exposure, media exposure, reactions to media, and life interruption-as correlates of posttraumatic stress disorder (PTSD) symptoms, depression, and anger. The final model yielded (n = 432), chi(2) (d = 12) = 7.4, p = .830; comparative fit index = 1.0, root mean square error of approximation = 0 [0, .04]. All aspects of proximity except direct exposure were associated with mental health outcomes. There was no moderation as a function of community versus police. Race moderated the relationship between life interruptions and negative outcomes; interruption was related to distress for White, but not Black community members. Based on group comparisons, community members reported more symptoms of PTSD and depression than law enforcement (etap (2) = .06 and .02, respectively). Black community members reported more PTSD and depression than White community members (etap (2) = .05 and .02, respectively). Overall, distress was high, and mental health interventions are likely indicated for some individuals exposed to the Ferguson events. PMID- 27254475 TI - Controlling the time evolution of mAb N-linked glycosylation, Part I: Microbioreactor experiments. AB - N-linked glycosylation is of key importance for the efficacy of many biotherapeutic proteins such as monoclonal antibodies (mAbs). Media components and cell culture conditions have been shown to significantly affect N-linked glycosylation during the production of glycoproteins using mammalian cell fed batch cultures. These parameters inevitably change in modern industrial processes with concentrated feed additions and cell densities beyond 2 * 107 cells/mL. In order to control the time-dependent changes of protein glycosylation, an automated microbioreactor system was used to investigate the effects of culture pH, ammonia, galactose, and manganese chloride supplementation on nucleotide sugars as well as mAb N-linked glycosylation in a time-dependent way. Two different strategies comprising of a single shift of culture conditions as well as multiple media supplementations along the culture duration were applied to obtain changing and constant glycosylation profiles. The different feeding approaches enabled constant glycosylation patterns throughout the entire culture duration at different levels. By modulating the time evolution of the mAb glycan pattern, not only the endpoint but also the ratios between different glycosylation structures could be modified. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1123-1134, 2016. PMID- 27254476 TI - Aromatic Side Chain Water-to-Lipid Transfer Free Energies Show a Depth Dependence across the Membrane Normal. AB - Quantitating and understanding the physical forces responsible for the interactions of biomolecules are fundamental to the biological sciences. This is especially challenging for membrane proteins because they are embedded within cellular bilayers that provide a unique medium in which hydrophobic sequences must fold. Knowledge of the energetics of protein-lipid interactions is thus vital to understand cellular processes involving membrane proteins. Here we used a host-guest mutational strategy to calculate the Gibbs free energy changes of water-to-lipid transfer for the aromatic side chains Trp, Tyr, and Phe as a function of depth in the membrane. This work reveals an energetic gradient in the transfer free energies for Trp and Tyr, where transfer was most favorable to the membrane interfacial region and comparatively less favorable into the bilayer center. The transfer energetics follows the concentration gradient of polar atoms across the bilayer normal that naturally occurs in biological membranes. Additional measurements revealed nearest-neighbor coupling in the data set are influenced by a network of aromatic side chains in the host protein. Taken together, these results show that aromatic side chains contribute significantly to membrane protein stability through either aromatic-aromatic interactions or placement at the membrane interface. PMID- 27254478 TI - NHC Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions of Aryl Boronate Esters with Perfluorobenzenes. AB - An efficient Suzuki-Miyaura cross-coupling reaction of perfluorinated arenes with aryl boronate esters using NHC nickel complexes as catalysts is described. The efficiencies of different boronate esters (p-tolyl-Beg, p-tolyl-Bneop, p-tolyl Bpin, p-tolyl-Bcat) and the corresponding boronic acid (p-tolyl-B(OH)2) in this type of cross-coupling reaction were evaluated (eg, ethyleneglycolato; neop, neopentylglycolato; pin, pinacolato; cat, catecholato). Aryl-Beg was shown to be the most reactive boronate ester among those studied. The use of CsF as an additive is essential for an efficient reaction of hexafluorobenzene with aryl neopentylglycolboronates. PMID- 27254477 TI - Calculating binding free energies of host-guest systems using the AMOEBA polarizable force field. AB - Molecular recognition is of paramount interest in many applications. Here we investigate a series of host-guest systems previously used in the SAMPL4 blind challenge by using molecular simulations and the AMOEBA polarizable force field. The free energy results computed by Bennett's acceptance ratio (BAR) method using the AMOEBA polarizable force field ranked favorably among the entries submitted to the SAMPL4 host-guest competition [Muddana, et al., J. Comput.-Aided Mol. Des., 2014, 28, 305-317]. In this work we conduct an in-depth analysis of the AMOEBA force field host-guest binding thermodynamics by using both BAR and the orthogonal space random walk (OSRW) methods. The binding entropy-enthalpy contributions are analyzed for each host-guest system. For systems of inordinate binding entropy-enthalpy values, we further examine the hydrogen bonding patterns and configurational entropy contribution. The binding mechanism of this series of host-guest systems varies from ligand to ligand, driven by enthalpy and/or entropy changes. Convergence of BAR and OSRW binding free energy methods is discussed. Ultimately, this work illustrates the value of molecular modelling and advanced force fields for the exploration and interpretation of binding thermodynamics. PMID- 27254480 TI - The Endoscopic Reference Score shows modest accuracy to predict histologic remission in adult patients with eosinophilic esophagitis. AB - BACKGROUND: The relationship between the severity of endoscopic signs scored according to the Endoscopic Reference Score (EREFS) and histopathologic signs of eosinophilic esophagitis (EoE) has not been sufficiently explored. We aimed to determine if the EREFS system predicts histopathologic activity in EoE patients. METHODS: We included 69 patients with EoE (age 35 [IQR 29-48] years; 80% male) who, between 2006 and 2014, underwent esophagogastroduodenoscopy (EGD) during which high-quality endoscopic images were taken and esophageal biopsy specimens were obtained. Per EGD, three or more depersonalized images were scored by an expert endoscopist, and histopathologic signs were scored by a pathologist with gastrointestinal expertise; both in a blinded fashion. The predictive values of endoscopic signs for disease activity (peak eosinophil count) were calculated. In addition, we measured the utility of the EREFS in the follow-up of 35 EoE patients. KEY RESULTS: Individual endoscopic signs did not correspond to the peak eosinophil count or other histopathologic signs. Although the composite fibrotic signs score, inflammatory signs score, and total EREFS correlated weakly to moderately with the peak eosinophil count, none of these scores had both high positive and negative predictive values for histopathologic disease activity. In the follow-up of 35 patients, lower peak eosinophil counts were not associated with a decrease in endoscopic abnormalities. CONCLUSIONS & INFERENCES: In adult patients with EoE, the EREFS system correlates with peak eosinophil counts, but their predictive value for disease activity is insufficient for clinical use. Therefore, biopsies remain indispensable for the assessment of disease activity. PMID- 27254481 TI - Association of Socioeconomic Status and Race/Ethnicity With Treatment and Survival in Patients With Medullary Thyroid Cancer. AB - IMPORTANCE: Medullary thyroid cancer (MTC) is a relatively rare neoplasm of the thyroid but accounts for 14% of thyroid cancer-related deaths. Female sex, young age, and stage at presentation have been found to predict survival and treatment. However, patterns of survival and treatment by socioeconomic status and race/ethnicity have not been fully described. OBJECTIVE: To determine whether socioeconomic status and race/ethnicity are associated with survival and treatment in patients with MTC. DESIGN, SETTING, AND PARTICIPANTS: Data for 1647 patients with MTC from January 1, 1998, to December 31, 2011, in the Surveillance, Epidemiology, and End Results (SEER) Program registry were examined. Data analysis was conducted from June 1, 2013, to July 31, 2014. MAIN OUTCOMES AND MEASURES: Differences in receipt of thyroidectomy and lymph node examination by race/ethnicity were examined using logistic regression models. Overall and disease-specific survival were examined by race/ethnicity using Kaplan-Meier survival curves and adjusted Cox proportional hazards regression models. RESULTS: Of the 1647 patients with MTC were 1192 white (72.4%), 139 black (8.4%), 222 Hispanic (13.5%), and 94 other races/ethnicities (5.7%). Of these, 1539 (93.4%) underwent surgical treatment. There were no differences in receipt of thyroidectomy by race/ethnicity; however, black patients (adjusted odds ratio, 0.61; 95% CI, 0.39-0.93) and female patients (adjusted odds ratio, 0.76; 95% CI, 0.59-0.99) were less likely to undergo lymph node examination compared with non Hispanic white and male patients. Black patients had lower overall (adjusted hazard ratio, 2.40; 95% CI, 1.45-3.98) and disease-specific survival (adjusted hazard ratio, 2.9; 95% CI, 1.64-5.14) compared with non-Hispanic white patients. CONCLUSIONS AND REVELANCE: In this population-based study of patients with MTC, black patients were less likely to have lymph node examination following surgery. Furthermore, Hispanic and black patients had poorer overall and disease-specific survival compared with non-Hispanic white patients after accounting for clinical factors. Racial/ethnic disparities exist in the type of treatment as well as outcomes in patients with MTC. PMID- 27254482 TI - Error Sensitivity to Environmental Noise in Quantum Circuits for Chemical State Preparation. AB - Calculating molecular energies is likely to be one of the first useful applications to achieve quantum supremacy, performing faster on a quantum than a classical computer. However, if future quantum devices are to produce accurate calculations, errors due to environmental noise and algorithmic approximations need to be characterized and reduced. In this study, we use the high performance qHiPSTER software to investigate the effects of environmental noise on the preparation of quantum chemistry states. We simulated 18 16-qubit quantum circuits under environmental noise, each corresponding to a unitary coupled cluster state preparation of a different molecule or molecular configuration. Additionally, we analyze the nature of simple gate errors in noise-free circuits of up to 40 qubits. We find that, in most cases, the Jordan-Wigner (JW) encoding produces smaller errors under a noisy environment as compared to the Bravyi Kitaev (BK) encoding. For the JW encoding, pure dephasing noise is shown to produce substantially smaller errors than pure relaxation noise of the same magnitude. We report error trends in both molecular energy and electron particle number within a unitary coupled cluster state preparation scheme, against changes in nuclear charge, bond length, number of electrons, noise types, and noise magnitude. These trends may prove to be useful in making algorithmic and hardware related choices for quantum simulation of molecular energies. PMID- 27254484 TI - Rapid Synthesis of Cobalt Nitride Nanowires: Highly Efficient and Low-Cost Catalysts for Oxygen Evolution. AB - Electrochemical splitting of water to produce hydrogen and oxygen is an important process for many energy storage and conversion devices. Developing efficient, durable, low-cost, and earth-abundant electrocatalysts for the oxygen evolution reaction (OER) is of great urgency. To achieve the rapid synthesis of transition metal nitride nanostructures and improve their electrocatalytic performance, a new strategy has been developed to convert cobalt oxide precursors into cobalt nitride nanowires through N2 radio frequency plasma treatment. This method requires significantly shorter reaction times (about 1 min) at room temperature compared to conventional high-temperature NH3 annealing which requires a few hours. The plasma treatment significantly enhances the OER activity, as evidenced by a low overpotential of 290 mV to reach a current density of 10 mA cm(-2) , a small Tafel slope, and long-term durability in an alkaline electrolyte. PMID- 27254483 TI - The recent fall in postperinatal mortality in New Zealand and the Safe Sleep programme. AB - AIM: Postneonatal mortality rates changed very little from 2000 until recently. There has been a decrease in mortality in New Zealand from 2009 to 2015. This study describes an infant Safe Sleep programme and postulates it is the cause for the recent decrease in deaths. METHODS: The Safe Sleep programme involved as follows: a focus on preventing accidental suffocation, a 'blitz' approach to SUDI education, the targeted provision of portable infant Safe Sleep devices (ISSD) and the development of Safe Sleep policy across all district health boards (DHBs). RESULTS: Participation in the education 'blitz' by health professionals exceeded one in 23 live births, distribution of Safe Sleep leaflets exceeded two for every live birth, and over 16 500 ISSDs have been distributed to vulnerable infants. Postperinatal mortality fell 29% from 2009 to 2015 (2.8 to 2.0/1000 live births). The fall has been greatest for Maori and in regions with the most intensive programmes. CONCLUSION: The recent fall in postperinatal mortality has not happened by chance. It is likely that the components of end-stage prevention strategy, a focus on preventing accidental suffocation, the education 'blitz', the targeted supply of ISSDs and strengthened health policy, have all contributed to varying degrees. PMID- 27254479 TI - Emerging roles for long noncoding RNAs in skeletal biology and disease. AB - Normal skeletal development requires tight coordination of transcriptional networks, signaling pathways, and biomechanical cues, and many of these pathways are dysregulated in pathological conditions affecting cartilage and bone. Recently, a significant role has been identified for long noncoding RNAs (lncRNAs) in developing and maintaining cellular phenotypes, and improvements in sequencing technologies have led to the identification of thousands of lncRNAs across diverse cell types, including the cells within cartilage and bone. It is clear that lncRNAs play critical roles in regulating gene expression. For example, they can function as epigenetic regulators in the nucleus via chromatin modulation to control gene transcription, or in the cytoplasm, where they can function as scaffolds for protein-binding partners or modulate the activity of other coding and noncoding RNAs. In this review, we discuss the growing list of lncRNAs involved in normal development and/or homeostasis of the skeletal system, the potential mechanisms by which these lncRNAs might function, and recent improvements in the methodologies available to study lncRNA functions in vitro and in vivo. Finally, we address the likely utility of lncRNAs as biomarkers and therapeutic targets for diseases of the skeletal system, including osteoarthritis, osteoporosis, and in cancers of the skeletal system. PMID- 27254485 TI - Oral Anticoagulants: The Move Beyond Warfarin. PMID- 27254486 TI - The relationship between brain-derived neurotrophic factor, irisin and cognitive skills of endurance athletes. AB - OBJECTIVE: The objective of this study was to assess the cognitive performance of endurance athletes and its relation with circulating brain-derived neurotrophic factor (BDNF) and irisin levels. METHODS: 26 endurance athletes (14 elite orienteers (mean +/- SD: age = 26.33 +/- 4.08, body weight = 70.33 +/- 4.64, body height = 177.7 +/- 6.1), 12 pentathletes (mean +/- SD: age = 29.42 +/- 5.32, body weight = 74.77 +/- 6.59, body height = 180.8 +/- 3.8)) and ten sedentary (mean +/ SD: age = 27.30 +/- 2.06, body weight = 76.65 +/- 12.50, body height = 176.9 +/- 5.2) men at almost same ages and educational levels participated in this study. Cognitive functions were analyzed with mini-mental-state examination (MMSE) and Isaacs' Set Test of Verbal Fluency (IST) tests. Insulin-like growth factor-1 (IGF 1), BDNF and irisin levels were measured in the blood samples. RESULTS: The MSSE and IST scores of the endurance athletes were higher than that of the sedentary control group (P < 0.05). Serum IGF-1 levels were higher in the pentathletes (111.18 +/- 22.26 ng mL(-1)) than the orienteers (85.89 +/- 19.32 ng mL(-1)) (P < 0.05). Plasma BDNF (2.78 +/- 0.81, 4.28 +/- 1.03, and 3.93 +/- 0.77 ng mL(-1) in the sedentary, orienteers and pentathletes, respectively) and irisin (3.25 +/- 0.70, 6.16 +/- 0.99, and 6.58 +/- 1.09 ug mL(-1) in the sedentary, orienteers and pentathletes, respectively) concentrations of the endurance trained athletes were higher than that of the sedentary control group (P < 0.05). Positive correlation between the cognitive function test results and BDNF and irisin concentrations were observed (P < 0.05). There was also a positive correlation between the circulating irisin and BDNF concentrations (P < 0.05). CONCLUSION: These results suggested that irisin and BDNF levels positively correlated with cognition in the endurance trained athletes. PMID- 27254488 TI - Erratum. PMID- 27254487 TI - The assessment and measurement of adult life stress: Basic premises, operational principles, and design requirements. AB - Life stress is a central factor in the onset and course of a wide range of medical and psychiatric conditions. Determining the precise etiological and pathological consequences of stress, though, has been hindered by weaknesses in prevailing definitional and measurement practices. The purpose of the current paper is to evaluate the primary strategies for defining and measuring major and minor acute life events, chronic stressors, and daily hassles as informed by 3 basic scientific premises. The first premise concerns the manner in which stress is conceptualized and operationally defined, and specifically we assert that stress measures must not conflate the stress exposure with the stress response. The second premise concerns how stress exposures are measured, and we provide guidelines for optimizing standardized and sensitive indicators of life stress. The third premise addresses the consequences of variations in the procedures for life event measurement with regard to the validity of the research designs employed. We show that life stress measures are susceptible to several sources of bias, and if these potential sources of bias are not controlled in the design of the research, spurious findings may result. Our goal is to provide a useful guide for researchers who consider life stress to be an important factor in their theoretical models of disease, wish to incorporate measures of life stress in their research, and seek to avoid the common pitfalls of past measurement practices. (PsycINFO Database Record PMID- 27254526 TI - Applying Judgment Analysis Theory and Methods to Obtain an Insight Into Clinical Judgments: Implementation and Findings With a Simulated Neonatal Intensive Care Unit Setup. AB - INTRODUCTION: Clinicians who provide acute care are required to quickly identify and judge the illness severity of patients who experience deterioration in their clinical state. Accuracy of judgments can only be tested with respect to a valid reference, but in most health care areas, there is no such score. Judgment analysis theory and methods are presented and proposed as a framework to obtain insight into clinical judgments. A study in a simulated neonatal intensive care unit setup is described to demonstrate the applicability of the proposed methodology. METHODS: Sixteen participants from a neonatal intensive care unit department reviewed 31 clips of simulated cases. The participants were directed to use a 5-point scale to rate their personal interpretation regarding the illness severity of the simulated patient. Judgment analysis techniques were used to identify the judgment capabilities of the participants and to determine factors that influence those capabilities. RESULTS: Most participants interpreted the clinical signs information consistently, but interpretation varied remarkably between clinicians, providing possible explanation to the differences between the clinicians' judgments. Significant correlations were found between the doctors' years of medical experience and attributes of their judgments. CONCLUSIONS: Judgment analysis can be used to obtain insight into clinical judgments and to identify and quantify factors that affect clinicians' judgments. Judgment analysis can promote health care by enhancing clinical assessment teaching, by providing objective and personalized feedback to team members about their judgment performance, and by introducing a unified and objective method to study elements that affect clinical judgments. PMID- 27254527 TI - More Than One Way to Debrief: A Critical Review of Healthcare Simulation Debriefing Methods. AB - STATEMENT: Debriefing is a critical component in the process of learning through healthcare simulation. This critical review examines the timing, facilitation, conversational structures, and process elements used in healthcare simulation debriefing. Debriefing occurs either after (postevent) or during (within-event) the simulation. The debriefing conversation can be guided by either a facilitator (facilitator-guided) or the simulation participants themselves (self-guided). Postevent facilitator-guided debriefing may incorporate several conversational structures. These conversational structures break the debriefing discussion into a series of 3 or more phases to help organize the debriefing and ensure the conversation proceeds in an orderly manner. Debriefing process elements are an array of techniques to optimize reflective experience and maximize the impact of debriefing. These are divided here into the following 3 categories: essential elements, conversational techniques/educational strategies, and debriefing adjuncts. This review provides both novice and advanced simulation educators with an overview of various methods of conducting healthcare simulation debriefing. Future research will investigate which debriefing methods are best for which contexts and for whom, and also explore how lessons from simulation debriefing translate to debriefing in clinical practice. PMID- 27254528 TI - Response to "Unlike History, Should a Simulator Not Repeat Itself?" Simulation in Healthcare 2015; 10(6): 331-335. PMID- 27254530 TI - Catalytic transfer hydrogenation of azobenzene by low-valent nickel complexes: a route to 1,2-disubstituted benzimidazoles and 2,4,5-trisubstituted imidazolines. AB - The one-pot synthesis of 1,2-disubstituted benzimidazoles by the transfer hydrogenation of azobenzene, using benzylamine as a hydrogen donor, sequential rearrangement of hydrazobenzene to semidine and further condensation with N benzylideneamine is reported, catalyzed by 2 mol% of [Ni(COD)2] : dippe. The N2 substitution on benzimidazole can be controlled by the selection of different azobenzenes and C2 substitution will only depend on the chosen benzylamine. The current methodology avoids the addition of external oxidants, which are needed in the classical benzimidazole synthesis. In addition, the byproduct, N benzylideneamine, obtained from dehydrogenation of benzylamine produced 2,4,5 trisubstituted imidazolines by cyclization and C-H functionalization, and this route was optimized with the use of 2 mol% of [Ni(COD)2] : 2PPh3. PMID- 27254529 TI - Endometrial Cancer Associated Symptoms: A Case-Control Study. AB - BACKGROUND: The majority of women with endometrial cancer (EC) present at an early stage with an associated 5-year survival rate of >90%. High rates of early detection are attributed to warning symptoms; however, the prevalence of such symptoms has not been well defined. METHODS: A case-control study was conducted assessing the prevalence of symptoms in EC patients at a large cancer center compared with healthy controls. Controls included patients seen for an annual gynecologic care visit (AV) or for a gynecological problem-based visit (PV). A self-administered questionnaire was given to all participants addressing EC associated symptoms, at the time of initial clinic visit. Odds ratios (ORs) were used to compare prevalence of symptoms between EC cases and controls. Logistic regression was used to determine the impact of menopausal status and obesity on symptom prevalence. RESULTS: The cases (n = 75) were significantly older than the AV (n = 203) and PV (n = 151) controls (59.7 vs. 49.8 vs. 51.0 years, p < 0.01), had a higher body mass index (35.5 vs. 29.4 vs. 30.9 kg/m2, p < 0.01), and were more likely to be postmenopausal (76% vs. 53.7% vs. 52.0%, p < 0.01). The cases were more likely to report postmenopausal bleeding (OR = 32.99 and 5.83, p < 0.01) and abnormal vaginal discharge (OR = 8.8 and 3.3, p < 0.01) compared with the AV and PV groups. Overall, 55.4% of cases reported abnormal vaginal discharge. CONCLUSIONS: Symptoms of both postmenopausal bleeding and abnormal vaginal discharge were significantly higher in EC compared with controls. The presence of such symptoms should raise concern for malignant disease and prompt immediate gynecological evaluation. PMID- 27254531 TI - Effect of Bright Light Exposure on Depression and Agitation in Older Adults with Dementia. AB - This study examined the effects of bright light exposure on three measures of depression and four measures of agitation in persons with dementia residing in long-term care. Using a randomized controlled design, participants were randomly assigned to receive either bright light (n = 30) or low intensity light (n = 30) for eight weeks. Bright light exposure was associated with significant improvement in depression and agitation, while participants receiving low intensity light displayed higher levels of depression and agitation or no significant change. Findings support the use of bright light exposure to reduce depression and agitation in this population. PMID- 27254532 TI - Exome sequencing identifies a novel nonsense mutation of HOXD13 in a Chinese family with synpolydactyly. AB - Synpolydactyly (SPD) is an autosomal dominant limb malformation with a distinctive combination of syndactyly and polydactyly. SPD is clinically heterogeneous and could be genetically classified into three types. The clinical phenotype of SPD is complicated by its variable expressivity. In the present study, whole exome sequencing (WES) was used to identify the affected gene(s) in a Chinese family with atypical SPD phenotype. Our results showed that a novel heterogenous nonsense mutation (c.556C > T, p.R186X) in HOXD13 was associated with this SPD case. Due to variable expressivity, the diagnosis of a clinical heterogenous disease such as SPD is usually difficult. Our results also suggested that WES is an efficient tool to assist with these diagnoses. PMID- 27254533 TI - An Unexpected Postvitrectomy Course. PMID- 27254534 TI - Macroporous p-GaP Photocathodes Prepared by Anodic Etching and Atomic Layer Deposition Doping. AB - P-type macroporous gallium phosphide (GaP) photoelectrodes have been prepared by anodic etching of an undoped, intrinsically n-type GaP(100) wafer and followed by drive-in doping with Zn from conformal ZnO films prepared by atomic layer deposition (ALD). Specifically, 30 nm ALD ZnO films were coated on GaP macroporous films and then annealed at T = 650 degrees C for various times to diffuse Zn in GaP. Under 100 mW cm(-2) white light illumination, the resulting Zn doped macroporous GaP consistently exhibit strong cathodic photocurrent when measured in aqueous electrolyte containing methyl viologen. Wavelength-dependent photoresponse measurements of the Zn-doped macroporous GaP revealed enhanced collection efficiency at wavelengths longer than 460 nm, indicating that the ALD doping step rendered the entire material p-type and imparted the ability to sustain a strong internal electric field that preferentially drove photogenerated electrons to the GaP/electrolyte interface. Collectively, this work presents a doping strategy with a potentially high degree of controllability for high-aspect ratio III-V materials, where the ZnO ALD film is a practical dopant source for Zn. PMID- 27254535 TI - Serotype/serogroup-specific antibiotic non-susceptibility of invasive and non invasive Streptococcus pneumoniae, Switzerland, 2004 to 2014. AB - Concurrent analysis of antibiotic resistance of colonising and invasive Streptococcus pneumoniae gives a more accurate picture than looking at either of them separately. Therefore, we analysed 2,129 non-invasive and 10,996 invasive pneumococcal isolates from Switzerland from 2004 to 2014, which spans the time before and after the introduction of the heptavalent (PCV7) and 13-valent (PCV13) conjugated pneumococcal polysaccharide vaccines. Serotype/serogroup information was linked with all antibiotic resistance profiles. During the study period, the proportion of non-susceptible non-invasive and invasive isolates significantly decreased for penicillin, ceftriaxone, erythromycin and trimethoprim/sulfamethoxazole (TMP-SMX). This was most apparent in non-invasive isolates from study subjects younger than five years (penicillin (p = 0.006), erythromycin (p = 0.01) and TMP-SMX (p = 0.002)). Resistant serotypes/serogroups included in PCV7 and/or PCV13 decreased and were replaced by non-PCV13 serotypes (6C and 15B/C). Serotype/serogroup-specific antibiotic resistance rates were comparable between invasive and non-invasive isolates. Adjusted odds ratios of serotype/serogroup-specific penicillin resistance were significantly higher in the west of Switzerland for serotype 6B (1.8; 95% confidence interval (CI): 1.4 4.8), 9V (3.4; 95% CI: 2.0-5.7), 14 (5.3; 95% CI: 3.8-7.5), 19A (2.2; 95% CI: 1.6 3.1) and 19F (3.1; 95% CI: 2.1-4.6), probably due to variations in the antibiotic consumption. PMID- 27254536 TI - Fracture risk calculation tool enhances dual-energy X-ray absorptiometry scan referral pathway in cirrhosis patients. AB - OBJECTIVES: Liver cirrhosis is associated with osteoporosis leading to an increased risk of fractures. We aimed to establish whether a risk stratification strategy using a fracture risk calculation tool (FRAX) to determine which patients should receive a dual-energy X-ray absorptiometry (DXA) scan is effective in reducing scan rates without compromising sensitivity for detecting osteoporosis. METHODS: A retrospective analysis of 252 patients with liver cirrhosis attending hepatoma surveillance clinics. Receiver operating characteristic analysis was performed to assess sensitivity and specificity at 10 year fracture risk thresholds of 5, 10 and 15%. RESULTS: DXA scans were performed among 252 patients. Mean age was 61.6+/-10.2 years, of which 53.2% were male. Cirrhosis aetiology was largely a result of alcohol excess (n=33.3%), chronic hepatitis C virus infection (n=20.2%) and nonalcoholic fatty liver disease (n=15.9%). The majority of patients were in good prognostic groups (87.4% Child Pugh A, 11.3% Child-Pugh B, 1.3% Child-Pugh C). Osteoporosis was present in 19.0% of those who underwent DXA scanning. The optimum 10-year fracture risk threshold was found to be 10% using the FRAX tool. This retained a high sensitivity of 95.8%, specificity 64.7%, and negative predictive value 98.5%. Introduction of a 10% FRAX threshold would result in a reduction of the DXA scanning rate to 46.8% of the current rate. CONCLUSION: A risk stratification strategy for DXA scanning using a fracture risk assessment tool (FRAX) and a 10-year fracture risk threshold of 10% leads to a significant reduction in scan rates without compromising osteoporosis detection rates. PMID- 27254537 TI - Method to assess the accuracy of scores in mortality prediction: more than receiver operating characteristic curve. PMID- 27254538 TI - In favour of early intervention for Budd-Chiari syndrome: another brick in the wall. PMID- 27254539 TI - Potential molecular aspects of Helicobacter pylori-related hyperplastic polyp development and progression. PMID- 27254541 TI - Remote MEG dipoles in focal cortical dysplasia at bottom of sulcus. AB - OBJECTIVE: To investigate whether the magnetoencephalography (MEG) single moving dipole (SMD) method could delineate the epileptic zone of focal cortical dysplasia (FCD) at the bottom of sulcus (FCDB). METHODS: We retrospectively analyzed 17 children (11 male; mean age 8.8 years, range 3-17 years) with FCD type II who underwent epilepsy surgery. We compared spatial congruence between the following: (1) MEG cluster and FCDB and (2) MEG cluster and FCD at the brain surface (FCDS). We measured the volume and depth of magnetic resonance imaging (MRI)-visible lesions to investigate whether they affect spatial congruence between MEG cluster and MRI-visible lesion. RESULTS: Eight children had FCDB and the other nine children had FCDS. The volume of MRI-visible lesions for FCDB ranged from 1,632 to 4,707 mm(3) (mean +/- standard deviation [SD] 3,095 +/- 1,211 mm(3) ). The depth of FCDB ranged from 19 to 33 mm (mean +/- SD 26 +/- 4 mm). The volume of MRI-visible lesion for FCDS ranged from 2,375 to 57,331 mm(3) (15,470 +/- 18,455 mm(3) ). There was a tendency for a smaller volume of MRI visible lesion for FCDB, relative to FCDS(p = 0.079). In FCDB, six children showed clusters of MEG dipoles and two children showed scattered MEG dipoles for interictal spikes. The spatial congruence between the MEG result and FCDB was partially overlapping in four children and discordant in another four children. In FCDS, eight children had MEG cluster and one child had MEG scatter alone. The spatial congruence between MEG result and FCDS was overlapping in eight of nine children (fully two; partially six) and discordant in one of nine children. Fifteen children (88%; FCDB eight; FCDS seven) became seizure-free after resective surgery. MEG spike dipole resection ratio in the cluster ranged from 4 100% (mean 67%) in 6 FCDB and 23-99% (mean 77%) in 8 FCDS. SIGNIFICANCE: The SMD method may drift MEG spike dipoles for FCDB. Lesionectomy can control seizures for four of eight patients in FCDB despite the remote MEG dipoles. The FCDB or FCDS partially overlapped with MEG cluster may have an extending/invisible epileptogenic zone consecutive to the MRI-visible lesion. PMID- 27254542 TI - Body Dissatisfaction and Its Correlates in 5- to 7-Year-Old Girls: A Social Learning Experiment. AB - There is limited research on cognitive risk factors for eating disorders among young girls despite accumulating evidence that body dissatisfaction and thin ideal internalization can begin to occur between 3 and 5 years of age. To improve upon the existing literature and significantly contribute to the prevention and intervention literature, the current study examined body dissatisfaction, thin ideal internalization, and self-objectification in girls between 5 and 7 years of age. The sample consisted of 151 mother-daughter dyads with 63 five-year-olds, 39 six-year-olds, and 49 seven-year-olds. Girls were interviewed about their body dissatisfaction, thin-ideal, and self-objectification. In addition, all mothers and daughters participated in an individual and joint mirror experiment. Levels of body dissatisfaction were consistent across 5- to 7-year-olds. Thin-ideal internalization was higher among 5-year-olds than 6- and 7-year-olds. In contrast, self-objectification was higher among 6- and 7-year-olds than 5-year old girls. Mother's body dissatisfaction significantly and positively predicted daughter's body dissatisfaction during the joint mirror experiment. Similarly, mother's body satisfaction significantly and positively predicted daughter's body satisfaction. Results from this study suggest that girls model their mothers' self-body talk. In addition, girls will change their positive or negative body responses after being exposed to their mothers' response. PMID- 27254544 TI - Electrospinning Directly Synthesized Porous TiO2 Nanofibers Modified by Graphitic Carbon Nitride Sheets for Enhanced Photocatalytic Degradation Activity under Solar Light Irradiation. AB - We report a direct approach to the fabrication of a composite made of porous TiO2 nanofibers (NFs) and graphitic carbon nitride (g-C3N4) sheets, by means of an angled two-nozzle electrospinning combined with calcination process. Different wt % amounts of g-C3N4 particles in a polymer solution from one nozzle and TiO2 precursors containing the same polymer solution from another nozzle were electrospun and deposited on the collector. Structural characterizations confirm a well-defined morphology of the TiO2/g-C3N4 composite in which the TiO2 NFs are uniformly attached on the g-C3N4 sheet. This proper attachment of TiO2 NFs on the g-C3N4 sheets occurred during calcination. The prepared composites showed the enhanced photocatalytic activity over the photodegradation of rhodamine B and reactive black 5 under natural sunlight. Here, the synergistic effect between the g-C3N4 sheets and the TiO2 NFs having anisotropic properties enhanced the photogenerated electron-hole pair separation and migration, which was confirmed by the measurement of photoluminescence spectra, cyclic voltammograms, and electrochemical impedance spectra. The direct synthesis approach that is established here for such kinds of sheetlike structure and porous NFs composites could provide new insights for the design of high-performance energy conversion catalysts. PMID- 27254545 TI - Hyperostosis Following Orbital Exenteration. AB - PURPOSE: To describe CT scan findings following orbital exenteration in 27 patients and to identify the factors involved in the development of post exenteration hyperostosis. METHODS: Noncomparative case series. The authors reviewed the charts of 27 patients ranging in age from 33 to 99 years, who underwent unilateral exenteration at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia and at the School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. Data regarding patient demographics, surgical procedure, clinical diagnosis, and preoperative and postoperative CT imaging of the orbits were obtained. The relationship between hyperostosis and postoperative time, gender, age, adjuvant radiotherapy, and cavity coverage was evaluated by multivariate stepwise logistic regression. RESULTS: Seventeen (73.9 %) orbits had postoperative orbital hyperostosis. No soft tissue masses were detected in the affected orbits except in 2 cases with tumor recurrence. The only factor associated with hyperostosis was immediate intraoperative socket rehabilitation (odds ratio = 0.13, 95% confidence interval: 0.01-0.89). There was an 87.0% lower chance of hyperostosis in patients whose socket was covered with musculocutaneous flaps. Sequential CT scans showed that orbital hyperostosis followed a specific pattern. Initially, bone thickening appeared as either uniform or undulating endo osteal minimal thickening along the roof and then on the lateral and medial walls. More advanced hyperostosis had a laminated/lamellated appearance progressing to homogeneous and diffuse circumferential bone thickening. New bone formation and bone overgrowth were late findings. Hyperostosis extended to involve the adjacent facial bone, more obviously on the maxilla. Some patients had minimal thickening of the adjacent frontal and squamous temporal bone. Over pneumatization of the paranasal sinuses was evident in all cases of hyperostosis. CONCLUSIONS: Development of hyperostosis following exenteration is not rare. Radiologists and surgeons should be aware of the need to monitor the orbital healing process closely to avoid misdiagnoses of tumor recurrence/radionecrosis or infection. Obliteration of the orbital cavity with musculocutaneous flaps significantly reduces the chances of bone hyperostosis. PMID- 27254543 TI - Hepatoma-derived Growth Factor Predicts Disease Severity and Survival in Pulmonary Arterial Hypertension. AB - RATIONALE: Pulmonary arterial hypertension (PAH) is a fatal disease, and pulmonary microvascular remodeling is an important contributor to PAH development. Therefore, we hypothesized that a circulating angiogenic factor could predict disease severity and survival. OBJECTIVES: We sought to assess the relationship of serum hepatoma-derived growth factor (HDGF) with PAH disease severity and survival. METHODS: Using a newly developed enzyme-linked immunosorbent assay, we evaluated circulating HDGF levels in two independent PAH cohorts and two different characterized control cohorts. Clinical and laboratory data were also used to assess the value of HDGF as a PAH prognostic biomarker. MEASUREMENTS AND MAIN RESULTS: Serum HDGF levels were significantly elevated in two independent PAH cohorts. Importantly, serum HDGF levels were not elevated in a noncardiac chronic disease cohort. Further, patients with elevated HDGF had significantly lower exercise tolerance, worse New York Heart Association functional class, and higher levels of N-terminal pro-brain natriuretic peptide. HDGF was a strong predictor of mortality, with an unadjusted hazard ratio of 4.5 (95% confidence interval, 1.9-10.3; P = 0.003 by log-rank test). In multivariable Cox proportional hazards models, elevated HDGF levels predicted decreased survival after being adjusted for age, PAH subtype, invasive hemodynamics, and N terminal pro-brain natriuretic peptide. CONCLUSIONS: Elevated HDGF was associated with worse functional class, exertional intolerance, and increased mortality in PAH, suggesting HDGF as a potential biomarker for predicting mortality and as having possible diagnostic value for distinguishing PAH from non-PAH. HDGF may add additional value in PAH risk stratification in clinical trials and may represent a potential target for future PAH drug development. PMID- 27254592 TI - Gibbs-Thomson Effect in Planar Nanowires: Orientation and Doping Modulated Growth. AB - Epitaxy-enabled bottom-up synthesis of self-assembled planar nanowires via the vapor-liquid-solid mechanism is an emerging and promising approach toward large scale direct integration of nanowire-based devices without postgrowth alignment. Here, by examining large assemblies of indium tin oxide nanowires on yttria stabilized zirconia substrate, we demonstrate for the first time that the growth dynamics of planar nanowires follows a modified version of the Gibbs-Thomson mechanism, which has been known for the past decades to govern the correlations between thermodynamic supersaturation, growth speed, and nanowire morphology. Furthermore, the substrate orientation strongly influences the growth characteristics of epitaxial planar nanowires as opposed to impact at only the initial nucleation stage in the growth of vertical nanowires. The rich nanowire morphology can be described by a surface-energy-dependent growth model within the Gibbs-Thomson framework, which is further modulated by the tin doping concentration. Our experiments also reveal that the cutoff nanowire diameter depends on the substrate orientation and decreases with increasing tin doping concentration. These results enable a deeper understanding and control over the growth of planar nanowires, and the insights will help advance the fabrication of self-assembled nanowire devices. PMID- 27254593 TI - Transcriptome profiles of metamorphosis in the ornamented pygmy frog Microhyla fissipes clarify the functions of thyroid hormone receptors in metamorphosis. AB - Anuran metamorphosis is an excellent system in which to study postembryonic development. Studies on Xenopus (Mesobatrachia) show that thyroid hormone receptors (TRs) regulate metamorphosis in a ligand-dependent manner by coordinating the action of hundreds of genes. However, whether this mechanism is conserved among amphibians is still unknown. To understand the molecular mechanism of this universal phenomenon, we report the transcriptional profiles of the three key developmental stages in Microhyla fissipes (Neobatrachia): premetamorphosis (PM), metamorphic climax (MC) and completion of metamorphosis (CM). In total, 2,293 differentially expressed genes were identified from comparisons of transcriptomes, and these genes showed stage-specific expression patterns. Unexpectedly, we found that TRalpha was highly expressed in Xenopus laevis and Bufo gargarizans at premetamorphosis but showed low expression in M. fissipes. In contrast, TRbeta was highly expressed during metamorphosis in M. fissipes and X. laevis. This result may imply that TRbeta is essential for initiating metamorphosis, at least in M. fissipes. Thus, our work not only identifies genes that are likely to be involved in Neobatrachia metamorphosis but also clarifies the roles of unliganded TRalpha in regulating tadpole growth and timing of metamorphosis, which may be conserved in anurans, and the role of liganded TRbeta in launching metamorphosis. PMID- 27254594 TI - Phagonaute: A web-based interface for phage synteny browsing and protein function prediction. AB - Distant homology search tools are of great help to predict viral protein functions. However, due to the lack of profile databases dedicated to viruses, they can lack sensitivity. We constructed HMM profiles for more than 80,000 proteins from both phages and archaeal viruses, and performed all pairwise comparisons with HHsearch program. The whole resulting database can be explored through a user-friendly "Phagonaute" interface to help predict functions. Results are displayed together with their genetic context, to strengthen inferences based on remote homology. Beyond function prediction, this tool permits detections of co-occurrences, often indicative of proteins completing a task together, and observation of conserved patterns across large evolutionary distances. As a test, Herpes simplex virus I was added to Phagonaute, and 25% of its proteome matched to bacterial or archaeal viral protein counterparts. Phagonaute should therefore help virologists in their quest for protein functions and evolutionary relationships. PMID- 27254595 TI - Localization of latency-associated nuclear antigen (LANA) on mitotic chromosomes. AB - In latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), viral gene expression is extremely limited and copy numbers of viral genomes remain constant. Latency-associated nuclear antigen (LANA) is known to have a role in maintaining viral genome copy numbers in growing cells. Several studies have shown that LANA is localized in particular regions on mitotic chromosomes, such as centromeres/pericentromeres. We independently examined the distinct localization of LANA on mitotic chromosomes during mitosis, using super resolution laser confocal microscopy and correlative fluorescence microscopy electron microscopy (FM-EM) analyses. We found that the majority of LANA were not localized at particular regions such as telomeres/peritelomeres, centromeres/pericentromeres, and cohesion sites, but at the bodies of condensed chromosomes. Thus, LANA may undergo various interactions with the host factors on the condensed chromosomes in order to tether the viral genome to mitotic chromosomes and realize faithful viral genome segregation during cell division. PMID- 27254596 TI - Rapid induction and persistence of paracrine-induced cellular antiviral states arrest viral infection spread in A549 cells. AB - The virus/host interaction is a complex interplay between pro- and anti-viral factors that ultimately determines the spread or halt of virus infections in tissues. This interplay develops over multiple rounds of infection. The purpose of this study was to determine how cellular-level processes combine to impact the spatial spread of infection. We measured the kinetics of virus replication (VSV), antiviral paracrine signal upregulation and secretion, spatial spread of virus and paracrine antiviral signaling, and inhibition of virus production in antiviral-exposed A549 human lung epithelial cells. We found that initially infected cells released antiviral signals 4-to-7h following production of virus. However, the subsequent rapid dissemination of signal and fast induction of a robust and persistent antiviral state ultimately led to a suppression of infection spread. This work shows how cellular responses to infection and activation of antiviral responses can integrate to ultimately control infection spread across host cell populations. PMID- 27254599 TI - Revealing stiffening and brittling of chronic myelogenous leukemia hematopoietic primary cells through their temporal response to shear stress. AB - Cancer cell transformation is often accompanied by a modification of their viscoelastic properties. When capturing the stress-to-strain response of primary chronic myelogenous leukemia (CML) cells, from two data sets of CD34+ hematopoietic cells isolated from healthy and leukemic bone marrows, we show that the mean shear relaxation modulus increases upon cancer transformation. This stiffening of the cells comes along with local rupture events, detected as reinforced sharp local maxima of this modulus, suggesting that these cancer cells respond to a local mechanical stress by a cascade of local brittle failure events. PMID- 27254598 TI - The potential use of cell-free-circulating-tumor DNA as a biomarker for prostate cancer. AB - INTRODUCTION: We are yet to identify an accurate, precise and non-invasive biomarker for the detection of prostate cancer. It would undoubtedly be useful to have a reliable and cost-effective biomarker to inform clinical practice, in order to make a non-invasive diagnosis and to predict risk of progression to aggressive prostate cancer. Since the detection of cell-free-circulating-tumor DNA in the body fluids of prostate cancer patients, a number of studies have been conducted to assess diagnostic and/or prognostic information. AREAS COVERED: In this literature review we evaluate the utility of cell-free-circulating-tumor-DNA for the development of a diagnostic and/or prognostic tool for prostate cancer. In addition, we identify potential areas for future research. Results from both quantitative and qualitative studies are presented. Expert commentary: Evidence for the suitability of a panel of DNA methylation markers for the non-invasive diagnosis of prostate cancer is strong. This panel would likely include the assessment of methylation status in gene promoter regions within the EDNR, GSTP1 and MDR genes. TIMP3 and APC show potential as diagnostic markers and should be further researched. Similarly, quantitation of cell-free-circulating-tumor-DNA in blood and urine requires further investigation. PMID- 27254600 TI - Health and the body: The Ingram Collection at the Royal College of General Practitioners (RCGP), London, UK. (3 March to 29 May 2016). AB - A new Ingram Collection exhibition, Health and the Body, opened for a period of two months at the Royal College of General Practitioners in London. The exhibition showcased paintings and sculptures by artists such as Eduardo Paolozzi, Barbara Hepworth, Geoffrey Clarke and Leon Underwood the artworks explored representations of the human body, and observed how these intersected with the history of general medical practice. PMID- 27254601 TI - Control of Integrated Task Sequences Shapes Components of Reaching. AB - Reaching toward an object usually consists of a sequence of elemental actions. Using a reaching task sequence, the authors investigated how task elements of that sequence affected feedforward and feedback components of the reaching phase of the movement. Nine right-handed adults performed, with their dominant and nondominant hands, 4 tasks of different complexities: a simple reaching task; a reach-to-grasp task; a reach-to-grasp and lift object task; and a reach-to-grasp, lift, and place object task. Results showed that in the reach-to-grasp and lift object task more time was allocated to the feedforward component of the reach phase, while latency between the task elements decreased. We also found between hand differences, supporting previous findings of increased efficiency of processing planning-related information in the preferred hand. The presence of task-related modifications supports the concept of contextual effects when planning a movement. PMID- 27254621 TI - ["Inflammaging" - aging as consequence of inflammation]. PMID- 27254622 TI - [Acute aortic syndrome]. AB - Acute aortic syndrome is the common denominator for acute events to the aortic wall and encompasses dissection of the aorta, intramural hematoma, formation of aortic ulcers and trauma to the aorta with an annual incidence of up to 35 cases/100.000 between 65 and 75 years of age. Both, inflammation and/or microtrauma at the level of the aortic media layer, and a genetic disposition are promoting elements of AAS, while the extent and anatomic involvement of the ascending aorta call for either surgical resection/repair in the proximal part of the aorta, or an endovascular solution for pathologies in the distal aorta; in all cases of dissection (regardless of location) reconstruction/realignment has been proven to portend better long-term outcomes (in addition to medical management of blood pressure). PMID- 27254623 TI - [Nutrition in dementia]. AB - Older people suffering from dementia are at increased risk of malnutrition due to various nutritional problems, and the question arises which interventions are effective in maintaining adequate nutritional intake and nutritional status in the course of the disease. In an international expert group, initiated by the European Society for Clinical Nutrition and Metabolism (ESPEN), 26 evidence-based recommendations for nutritional care of older persons with dementia have been developed, covering the topics of screening and assessment of malnutrition, strategies to support oral nutrition, oral supplementation and artificial nutrition. This article is a short version of the guideline. PMID- 27254624 TI - [Treatment of metastatic malignant melanoma]. PMID- 27254625 TI - [Health care of refugees - A short review with focus on infectious diseases]. AB - Few guidelines for health care of refugees exist in Germany. Screening as a part of initial health checks as well as general organisation of early health care for refugees is very heterogenous across different regions. Current experience will be relevant to develop integrated health care models. Prevention and care of infectious diseases are an important part of early health care for refugees, even if non-communicable diseases and mental health conditions should also be considered in every effort to design early health care models. We are presenting a pragmatic review of current evidence for prevention and care of tuberculosis, HIV, chronic viral hepatitis and other infectious diseases. More evidence is needed to assess morbidity and efficacy of early health care interventions and integrated care models in refugees. PMID- 27254626 TI - [Coagulation disorders in the intensive care unit - what is new?]. AB - The phase III non-vitamin K dependent oral anticoagulants (NOAC) studies and recently published real world data on the use of dabigatran and rivaroxaban have shown that the bleeding profile in particular of intracranial and other life threatening bleeding of NOAC is more favourable than that of warfarin. In case of a bleeding complication in a patient treated with a NOAC the recently updated EHRA practical guide offers management strategies. Idarucizumab, the specific antidot for dabigatran is approved to reverse the anticoagulant effect of dabigatran-treated patients who have serious bleeding and require an urgent procedure. Andexanet alfa, a specific antidot for direct and indirect factor Xa inhibitors will be available in the future. The frequency of thrombocytopenia in ICU patients is high whereas the heparin induced thrombocytopenia (HIT) only counts for a small minority of patients with thrombocytopenia. To avoid an overdiagnosis of HIT a reliable and complete clinical and laboratory workup has to be performed. New immunoassays have been developed to provide results within a short period of time. These tests appear to have improved diagnostic accuracy compared with ELISAs in patients with suspected HIT and may reduce misdiagnosis and overtreatment. Acquired haemophilia (AH) is a rare and often life threatening bleeding disorder caused by autoantibodies against factor VIII. Susoctocog alfa is a B-domain deleted recombinant factor VIII porcine sequence that has recently been approved to treat severe bleeding in patients with AH. Susoctocog alfa offers the ability to effectively titrate and monitor dosing based on factor VIII activity levels. PMID- 27254627 TI - [The new 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation]. AB - In 2015 the European Society of Cardiology published a new version of the guidelines for the management of acute coronary syndromes without persistent ST segment elevation. The current communication addresses some of the most important updates: introduction of the 1-hour diagnostic algorithm with high-sensitivity troponin assays, specified time lines for the invasive strategy, new recommendations for catheter intervention and peri-interventional antithrombotic therapy as well as new aspects of secondary prevention. PMID- 27254628 TI - [Primary and secondary arterial hypertension - update 2016]. AB - In patients with hypertension without diabetes and with an increased risk of cardiovascular complications a blood pressure of below 130 mmHg should be targeted. Hypertensive patients with an age above 80 years should be treated in the same way as younger hypertensive patients if they are otherwise healthy and functionally independent. On the other hand frail elderly patients could have an increased morbidity and mortality with intensive blood pressure control. In patients with resistant hypertension spironolactone was the most effective drug when given in addition to their baseline drugs (ACE-inhibitor/angiotensin receptor antagonist, calcium channel blocker and thiazide diuretic). PMID- 27254629 TI - [Treatment of refractory asthma with antibodies]. AB - Current guidelines of the global initiative for asthma (GINA) recommend the addition of biologics in step 5 of the stepwise asthma treatment approach. This review gives an overview on the effects and the clinical role of antibodies targeting immunoglobulin E, IgE (Omalizumab), Interleukin-5, IL-5 (Mepolizumab, Reslizumab) or the IL-5 receptor (Benralizumab). In addition, potential future treatment options of refractory asthma with antibodies (for instance Dupilumab) are discussed. PMID- 27254630 TI - [Immune system and rheumatic diseases in the elderly]. AB - Impairments of the immune system play an important role in all immun-mediated rheumatic diseases. Recently, the following news were reported: . Early aging of the immune system with thymus insufficiency has now been reported for both patients with rheumatoid arthritis and axial spondyloarthritis, without prethymic lack of progenitors at least in rheumatoid arthritis.. . For giant cell arteritis, the most frequent vasculitis in the elderly, an increased expression of IL-17A in temporal artery biopsies coincides with good prognosis and reponse to glucocorticoids.. . Concerning immunosenescence in systemic lupus erythematosus, BAFF appears to have an important role for relapses after B-cell depletion.. For the future it can be anticipated that the use of unified classification criteria for rheumatic diseases (as with the new 2012 EULAR / ACR classification criteria for polymyalgia rheumatica) will ensure better comparability of immunological studies also in the elderly. PMID- 27254631 TI - [Acute-on-chronic liver failure - new Definition of a complex clinical picture]. AB - Acute-on-chronic liver failure (ACLF) is characterized by a sudden onset of decompensation in patients with preexisting liver disease followed by subsequent organ failure and high short-term mortality. ACLF is extremely heterogeneous in terms of predisposing stage of liver disease, precipitating events, and the course of organ failure and has been defined differently by different medical associations in the East and in the West. A recent consensus working definition is the basis for further research in order to understand underlying pathophysiological mechanisms, to establish diagnostic and prognostic biomarkers, and to implement risk-adapted treatment strategies. PMID- 27254632 TI - [35-year old woman with fever and sudden leg pain]. PMID- 27254633 TI - [Borderline leprosy as a rare differential diagnosis]. AB - History and clinical findings | A 42-year-old migrant from Brazil presented with persistent sensory disturbances, skin discolorations and local alopecia in the upper limbs. Decisive for the presentation in our Tropical Medicine Clinic were new occurrences of severe pain and redness and swelling in the area of the lesions that had already been assessed by a number of medical specialists without a clear diagnosis could be made. Investigations and diagnosis | The histological analysis of skin biopsies showed perivascular, perineural, periadnexial lymphocytic and granulomatous dermatitis. In a direct microbiological preparation individual acid fast bacilli could be detected (Ziehl-Neelsen stain). The electroneurographical examination demonstrated a sensitive peripheral-neurogenic damage with emphasis on the right median nerve and the left ulnar and radial nerves. Thermography revealed an increased heating or cooling threshold. The serological investigation by ELISA for IgM antibodies against the phenolic glycolipid (PGL-1) was positive (titer 1 : 1200). In summary, the diagnosis of borderline leprosy (infection with Mycobacterium leprae) with transition to multibacillary leprosy (according to WHO) and leprosy reaction type 1 was made. Treatment and course | We initiated an oral antimycobacterial therapy (multidrug therapy, MDT) with rifampin, clofazimine and dapsone for 12 months (WHO regimen for multibacillary leprosy). Leprosy reaction type 1 was treated with prednisolone and by increasing the dose of clofazimine. Analgesic therapy on demand was carried out with nonsteroidal anti-inflammatory drugs (ibuprofen). MDT and successful management of leprosy reaction lead to a rapid improvement of symptoms. Conclusions | Leprosy is an infectious disease occurring only rarely in Germany (average incidence of 1-2 cases per year) that is diagnosed almost exclusively among migrants. Main symptoms comprise non-itchy, reddish, touch insensitive skin lesions or nerve deficits. The diagnosis is based primarily on the clinical presentation, supplemented by pathogen detection, histology, neurophysiological findings and serology. Standard therapy is a combination of rifampin, clofazimine and dapsone (WHO scheme) for at least 6 months. PMID- 27254634 TI - Associations of the Novel Polymorphisms of Periostin and Platelet-Derived Growth Factor Receptor-Like Genes with Egg Production Traits in Local Chinese Dagu Hens. AB - The periostin (POSTN) and platelet-derived growth factor receptor-like (PDGFRL) genes are implicated in regulation of hen ovarian development. In the present study, these genes were explored as possible molecular markers associated with egg production, egg weight and body weight in Chinese Dagu hens. Samples were analyzed using the PCR-single strand conformation polymorphism (PCR-SSCP) method, followed by sequencing analysis, and three novel single nucleotide polymorphisms (SNPs) were identified within the candidate genes. Among them, an A/T transversion at base position 2727 in intron 2 of POSTN gene was found to be polymorphic and named SNP A2727T; and two transitions, G/A at position 6761 and A/G at base 6839 in exon 2 of PDGFRL gene were detected and named SNPs G6761A and A6839G, respectively. For the SNP A2727T, a total of 360 Dagu hens were classified as AA and AB genotypes, allele A was found present at a higher frequency. Moreover, the AA genotype was significantly correlated with higher hen housed egg production (HHEP) at 43, 57, and 66 weeks (wks) of age and with a higher egg weight (EW) at 30 wks (P < 0.05). For the two linked SNPs (G6761A and A6839G) in the PDGFRL fragment, the hens were typed into TT, TC and CC genotypes, with the T allele shown to be dominant. The TT genotype was correlated with higher HHEP at 57 and 66 wks of age; genotype CC associated with the highest body weight and EW at 30 and 43 wks (P < 0.05), while it was correlated with the lowest HHEP at 57 and 66 wks of age (P < 0.05). Furthermore, five haplotypes were reconstructed based on these SNPs, with the AATT haplotype associated with the highest HHEP at 43 to 66 wks of age and higher EW at 30 wks (P < 0.05). Collectively, these SNPs identified in this study might be used as a potential molecular marker favorable to genetic improvement of egg productivity in chicken breeding. PMID- 27254635 TI - Foreword. PMID- 27254636 TI - A Review of Organ Transplantation: Heart, Lung, Kidney, Liver, and Simultaneous Liver-Kidney. AB - Heart, lung, kidney, liver, and simultaneous liver-kidney transplants share many features. They all follow the same 7-step process, the same 3 immunosuppressant medications, and the same reason for organ transplantation. Organs are transplanted because of organ failure. The similarities end there. Each organ has its unique causes for failure. Each organ also has its own set of criteria that must be met prior to transplantation. Simultaneous liver-kidney transplant criteria vary per transplant center but are similar in nature. Both the criteria required and the 7-step process are described by the United Network of Organ Sharing, which is a private, nonprofit organization, under contract with the US Department of Health and Human Services. Its function is to increase the number of transplants, improve survival rates after transplantation, promote safe transplant practices, and endorse efficiency. The purpose of this article is to review the reasons transplant is needed, specifically heart, lung, kidney, liver, and simultaneous liver-kidney, and a brief overview of the transplant process including criteria used, contraindications, and medications prescribed. PMID- 27254637 TI - The Path From Heart Failure to Cardiac Transplant. AB - Heart failure is a progressive and fatal disease impacting millions of American each year. Divided into stages, heart failure presents with progressive symptoms requiring a wide range of medical treatments. Treatments include diet and lifestyle changes, medications, electrical therapies (defibrillator and/or cardiac resynchronization therapy), as well as mechanical circulatory support. Cardiac transplant is the gold standard treatment of heart failure, although the availability of donors limits the utility of a cardiac transplant. This article outlines heart failure treatments and the indications, contraindications, and pretransplant evaluation for a cardiac transplant. Information on the allocation of donor hearts and donor characteristics is also included for the reader. PMID- 27254638 TI - Cardiac Transplant Postoperative Management and Care. AB - Heart failure impacts a multitude of individuals each year. Treatment is based on the progression of the disease and severity of symptoms. Cardiac transplant is the gold standard treatment of advanced heart failure, although the availability of organs limits the number of transplants received each year. Postoperative care and monitoring for cardiac transplant is complex and requires specialized nurses and providers at transplant centers for successful outcomes. This article outlines cardiac transplant from preoperative care through transplant, as well as posttransplant monitoring and care including discharge. Special attention is focused on management in the intensive care unit setting and potential complications that can occur in the immediate postoperative period. Interventions for potential complications are also highlighted. PMID- 27254639 TI - Immunosuppression in Solid-Organ Transplantation: Essentials and Practical Tips. AB - A multidisciplinary team approach is essential for successful management of patients with solid-organ transplant. Transplant nursing encompasses care and support of transplant recipients as well as caregivers and organ donors through all phases of transplantation, from pretransplant evaluation to posttransplant recovery and maintenance. The field of solid-organ transplantation has advanced rapidly, and new treatments continue to emerge. Nurses who are responsible for the care of transplant recipients should have a knowledge base in transplant immunology and pharmacology. This review discusses mechanism of action, indication, side effects, and drug interactions of commonly used immunosuppressive medications in solid-organ transplantation. Nonoral routes of drug administration, therapeutic drug monitoring, and patient monitoring strategies are also included as practical tips for bedside nurses who are responsible for delivery of direct patient care and education of patients and their caregivers. This review focuses on the following medications: antithymocyte globulins, basiliximab, alemtuzumab, corticosteroids, tacrolimus, cyclosporine, azathioprine, mycophenolate mofetil/mycophenolate sodium, sirolimus, everolimus, belatacept, intravenous immunoglobulin, and rituximab. PMID- 27254640 TI - CRRT Regional Anticoagulation Using Citrate in the Liver Failure and Liver Transplant Population. AB - Regional citrate for continuous renal replacement therapy (CRRT) use in patients with liver failure or post-liver transplant has been considered a contraindication because of the risk of citrate toxicity development. Regional citrate has the benefit of decreased bleeding risks over systemic anticoagulation; therefore, it is of great benefit to the coagulopathic and surgical populations. This article analyzes current empiric data and compares with a case study specifically related to liver failure, liver transplant, and CRRT use. We found that the use of a total serum to ionized calcium ratio was much more reliable in measuring liver function than liver enzyme figures. This when paired with a citrate-reduction guideline based on serum to ionized calcium ratios provided effective, early management of citrate toxicity. Using new measurements to calculate liver metabolism of citrate and using a new citrate reducing guideline allow the bedside practitioner to use regional citrate anticoagulation in patients with liver failure and liver transplant who require CRRT. PMID- 27254641 TI - Postoperative Care of a Liver Transplant Recipient Using a Classification System: Type A (Stable) Versus Type B (Unstable). AB - Liver transplantation has become an effective and valuable option for patients with end-stage liver disease and hepatocellular carcinoma. Liver failure, an acute or chronic condition, results in impaired bile production and excretion, clotting factor production, protein synthesis, and regulation of metabolism and glucose. Some acute conditions of liver disease have the potential to recover if the liver heals on its own. However, chronic conditions, such as cirrhosis, often lead to irreversible disease and require liver transplantation. In this publication, we review the pathophysiology of liver failure, examine common conditions that ultimately lead to liver transplantation, and discuss the postoperative management of patients who are either hemodynamically stable (type A) or unstable (type B). PMID- 27254642 TI - Pharmacologic Strategies to Prevent Blood Loss and Transfusion in Orthotopic Liver Transplantation. AB - Patients undergoing orthotopic liver transplantation are at risk of both life threatening blood loss and thrombosis due to preexisting liver dysfunction and major intra- and postoperative coagulopathy. Traditional laboratory markers of hemostasis and coagulopathy are often inadequate to describe the alterations. Whole blood global viscoelastic tests, thromboelastography, and thromboelastometry may provide more complete pictures of the hematologic derangements and allow for more targeted therapy to prevent blood loss and massive transfusion. Antifibrinolytic medications such as aprotinin, tranexamic acid, and [Latin Small Letter Open E]-aminocaproic acid have been used successfully to reduce blood loss and the need for transfusion, although most published data are from small prospective trials or larger retrospective cohorts. Recombinant factor VIIa has not been shown to improve outcomes. Although transfusion needs have been associated with adverse outcomes, no studied medications for prevention of blood loss and transfusion have been associated with improved mortality or graft survival post-liver transplant. PMID- 27254643 TI - Pediatric Liver Transplantation: Unique Concerns for the Critical Care Team. AB - Liver transplantation originated in children more than 50 years ago, and these youngest patients, while comprising the minority of liver transplant recipients nationwide, can have some of the best and most rewarding outcomes. The indications for liver transplantation in children are generally more diverse than those seen in adult patients. This diversity in underlying cause of disease brings with it increased complexity for all who care for these patients. Children, still being completely dependent on others for survival, also require a care team that is able and ready to work with parents and family in addition to the patient at the center of the process. In this review, we aim to discuss diagnoses of particular uniqueness or importance to pediatric liver transplantation. We also discuss the evaluation of a pediatric patient for liver transplant, the system for allocating them a new liver, and also touch on postoperative concerns that are unique to the pediatric population. PMID- 27254644 TI - Looking Outside: Summer Camp for Children Who Have Undergone a Solid-Organ Transplant. AB - A high-quality critical care team is an essential component of any successful organ transplant program. From pretransplant care to the crucial postoperative period, its importance cannot be discounted. However, because of the focused nature of work in an intensive care unit (ICU), all too often members of the ICU team are not able to see and appreciate the ultimate fruits of their labor. These are factors that can contribute to the high rates of burnout and turnover among ICU teams. This article presents the concept of a summer camp for children who have received a solid-organ transplant. We discuss a vehicle by which ICU staff as well as other members of a patient's care team can gain a better appreciation of the full nature of both medical and, perhaps more importantly in this situation, nonmedical goals and outcomes in pediatric transplantation. We review our institutional experience running a summer camp for these children, discuss some of the important points in making such a camp successful, and discuss potential benefits to the campers as well as those taking care of them. PMID- 27254645 TI - What Is Being Done to Increase Organ Donation? AB - The need for organs greatly outnumbers the amount of organs donated for transplantation. This is true for all countries around the world. Many organizations globally have been created to solve this problem. Spain has been very successful with its drive to increase organ donation. Educational campaigns are a great tool being utilized by all countries and the medical communities to promote a positive perception of organ donation. These campaigns include using the television industry, raising money for travel expenses, and education seminars. This article looks at the different groups and programs aimed at increasing organ donation. PMID- 27254646 TI - Letter to the Editor. PMID- 27254647 TI - Diacylglycerol acyl transferase: A pathogenicity related gene in Colletotrichum gloeosporioides. AB - To gain more insight into the molecular mechanisms of Colletotrichum gloeosporioides pathogenesis, restriction enzyme-mediated integration (REMI) mutagenesis identified the mutants of C. gloeosporioides impaired in pathogenicity. Transformants screened for defects in pathogenicity using detached leaves and fruits. Of the 20 REMI transformants tested, two mutants (H4 and H7) showed reduced pathogenicity on leaves of apple, kiwi, mango, peach, and fruits of guava, apple, and capsicum. One tagged gene from the genome sequence of mutant H4 was recovered by inverse PCR. Sequence analysis of the tagged site in mutant H4 revealed insertion in diacylglycerol acyltransferase gene which encodes diacylglycerol acyltransferase enzyme, catalyzing the steps involved in the biosynthesis of triacylglycerol, an important component of biological membranes and source of energy. Therefore, tagging of diacylglycerol acyltransferase gene in mutant H4 resulted in reduced pathogenicity, indicating possible role of this gene in pathogenicity of C. gloeosporioides. PMID- 27254648 TI - The Importance of Role Models in Research. PMID- 27254649 TI - Notes from the Field: Increase in Neisseria meningitidis-Associated Urethritis Among Men at Two Sentinel Clinics - Columbus, Ohio, and Oakland County, Michigan, 2015. AB - Neisseria meningitidis (Nm) urogenital infections, although less common than infections caused by Neisseria gonorrhoeae (Ng), have been associated with urethritis, cervicitis, proctitis, and pelvic inflammatory disease. Nm can appear similar to Ng on Gram stain analysis (gram-negative intracellular diplococci) (1 5). Because Nm colonizes the nasopharynx, men who receive oral sex (fellatio) can acquire urethral Nm infections (1,3,5). This report describes an increase in Nm associated urethritis in men attending sexual health clinics in Columbus, Ohio, and Oakland County, Michigan. PMID- 27254650 TI - The catalytic effect of water, water dimers and water trimers on H2S + (3)O2 formation by the HO2 + HS reaction under tropospheric conditions. AB - In this article, the reaction mechanisms of H2S + (3)O2 formation by the HO2 + HS reaction without and with catalyst X (X = H2O, (H2O)2 and (H2O)3) have been investigated theoretically at the CCSD(T)/6-311++G(3df,2pd)//B3LYP/6 311+G(2df,2p) level of theory, coupled with rate constant calculations by using conventional transition state theory. Our results show that in the presence of catalyst X (X = H2O, (H2O)2 and (H2O)3) into the channel of H2S + (3)O2 formation, the reactions between the SH radical and HO2(H2O)n (n = 1-3) complexes are more favorable than the corresponding reactions of the HO2 radical with HS(H2O)n (n = 1-3) complexes due to the lower barrier of the former reactions and the higher concentrations of HO2(H2O)n (n = 1-3) complexes. Meanwhile, the catalytic effect of water, water dimers and water trimers is mainly taken from the contribution of a single water vapor molecule, since the total effective rate constant of HO2H2O + HS and H2OHO2 + HS reactions was, respectively, larger by 7 9 and 9-12 orders of magnitude than that of SH + HO2(H2O)2 and SH + HO2(H2O)3 reactions. Besides, the enhancement factor of water vapor is only 0.37% at 240 K, while at high temperatures, such as 425 K, the positive water vapor effect is enhanced up to 38.00%, indicating that at high temperatures the positive water effect is obvious under atmospheric conditions. Overall, these results show how water and water clusters catalyze the gas phase reactions under atmospheric conditions. PMID- 27254651 TI - A masked negative self-esteem? Implicit and explicit self-esteem in patients with Narcissistic Personality Disorder. AB - The mask model of narcissism states that the narcissistic traits of patients with NPD are the result of a compensatory reaction to underlying ego fragility. This model assumes that high explicit self-esteem masks low implicit self-esteem. However, research on narcissism has predominantly focused on non-clinical participants and data derived from patients diagnosed with Narcissistic Personality Disorder (NPD) remain scarce. Therefore, the goal of the present study was to test the mask model hypothesis of narcissism among patients with NPD. Male patients with NPD were compared to patients with other PD's and healthy participants on implicit and explicit self-esteem. NPD patients did not differ in levels of explicit and implicit self-esteem compared to both the psychiatric and the healthy control group. Overall, the current study found no evidence in support of the mask model of narcissism among a clinical group. This implicates that it might not be relevant for clinicians to focus treatment of NPD on an underlying negative self-esteem. PMID- 27254652 TI - Effects of repetitive transcranial magnetic stimulation over supplementary motor area in patients with schizophrenia with obsessive-compulsive-symptoms: A pilot study. AB - In patients with schizophrenia, obsessive-compulsive symptoms (OCS) are associated with lower rates of quality of life and polypharmacy. No previous controlled studies have tested the efficacy of repetitive transcranial magnetic stimulation (rTMS) on the treatment of OCS in this population. The present study examined the therapeutic effects of rTMS applied to the supplementary motor area (1Hz, 20min, 20 sessions) on OCS and general symptoms in patients with schizophrenia or schizoaffective disorder, and whether this intervention can produce changes in plasma levels of brain derived neurotrophic factor (BDNF). A double-blind randomized controlled trial was conducted. Active and sham rTMS were delivered to 12 patients (6 on each group). Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Brief Psychiatric Rating Scale (BPRS) scores, as well as BDNF levels, were assessed before, after, and 4 weeks after treatment. rTMS did not significantly change the outcomes after treatment and on the follow-up (Y-BOCS: Wald's X(2)=3.172; p=0.205; BPRS: X(2)=1.629; p=0.443; BDNF: X(2)=2.930; p=0.231). There seemed to be a trend towards improvement of BPRS scores 4 weeks after rTMS treatment comparing with sham (Cohen's d=0.875, with 32.9% statistical power). No side effects were reported. Future studies with larger sample sizes are needed. PMID- 27254656 TI - Is Obesity in Adolescent Idiopathic Scoliosis Associated With Larger Curves and Worse Surgical Outcomes? AB - STUDY DESIGN: A multicenter retrospective study of preoperative characteristics and surgical outcomes in adolescent idiopathic scoliosis (AIS). OBJECTIVE: To determine the effect of obesity on (i) curve magnitude at first presentation to an orthopedic surgeon, and (ii) surgical outcomes. SUMMARY OF BACKGROUND DATA: Clinical findings for scoliosis may be less apparent in overweight adolescents. The effect of obesity on curve magnitude at presentation to an orthopedic surgeon has not been studied. It is unclear whether obesity is associated with worse surgical outcomes in AIS. METHODS: Demographic, radiographic, perioperative, and complications data were collected on AIS patients who had undergone posterior spinal fusion (PSF). Descriptive and inferential analyses were conducted to compare healthy-weight (HW) [body mass index percentile for age (BMI%) <= 84], overweight (OW; BMI% >= 85), and obese (OB; BMI% >= 95) adolescents. RESULTS: We analyzed 588 patients (454 HW, 134 OW, and 71 OB). In comparison with the HW adolescents, major curve magnitude at presentation to orthopedics was larger in the OW adolescents (49.3 degrees vs. 43.9 degrees ) (P < 0.0001) and OB adolescents (50.4 degrees vs. 43.9 degrees ) (P = 0.001). The OW and OB groups had increased preoperative major curve magnitude [(59.1 degrees vs. 55.4 degrees ) (P = 0.001); (59.9 degrees vs. 55.4 degrees ) (P = 0.001)], preoperative minor curve magnitude [(42.2 degrees vs. 37.2 degrees ) (P < 0.0001); (43.0 degrees vs. 37.2 degrees ) (P = 0.001)], preoperative thoracic kyphosis [(30.8 degrees vs. 25.7 degrees ) (P < 0.0001); (33.7 degrees vs. 25.7 degrees ) (P < 0.0001)], and surgical time [(307 vs. 276 mins) (P = 0.009); (320 vs. 276 mins) (P = 0.005)] than the HW group.Subgroup analysis of the patients with a minimum 2-year follow-up (n = 245) showed a trend towards a higher complication rate in the OB group (47.8% vs. 28.3%) (P = 0.054). The OB group had significantly more superficial infections than the HW group (13.0% vs. 1.6%) (P = 0.001). CONCLUSION: OW patients with AIS have a larger curve magnitude at presentation to an orthopedic surgeon. OW patients who undergo PSF for AIS have increased surgical times. OB patients may be at higher risk of postoperative complications. LEVEL OF EVIDENCE: 3. PMID- 27254657 TI - Use of S2-Alar-iliac Screws Associated With Less Complications Than Iliac Screws in Adult Lumbosacropelvic Fixation. AB - STUDY DESIGN: Retrospective comparative study. OBJECTIVE: To compare clinical and radiographic outcomes between the S2-alar-iliac (S2AI) and the iliac screw (IS) techniques in the adult population and clarify the clinical strength of S2AI screws. SUMMARY OF BACKGROUND DATA: S2AI screws have been described as an alternative method for lumbosacropelvic fixation in place of ISs. The S2AI technique has several advantages with lower prominence, increased ability to directly connect to proximal instrumentation, less extensive dissection of tissue, and enhanced biomechanical strength over the IS technique. However, the clinical significance of these advantages remains unclear. METHODS: A single center retrospective review of patients who underwent lumbosacropelvic fixation yielded 25 IS group patients and 65 S2AI group patients. Baseline demographic information, postoperative complications, pain and functional outcomes, and screw related outcomes were collected. RESULTS: The S2AI group had lower rates of reoperation (8.8% vs. 48.0%, P < 0.001), surgical site infection (SSI) (1.5% vs. 44.0%, P < 0.001), wound dehiscence (1.5% vs. 36.0%, P < 0.001), and symptomatic screw prominence (0.0% vs. 12.0%, P = 0.02) than the IS group, whereas rates of L5-S1 pseudarthrosis, proximal junctional failure, and sacroiliac joint pain were similar in both groups. Statistically significant pain relief and functional recovery were achieved in both groups without any significant intergroup differences. On multivariate analyses, age [odds ratio (OR) = 0.91, P = 0.004] and S2AI instrumentation (OR = 0.08, P < 0.001) were protective of reoperation, whereas diabetes mellitus (OR = 10.9, P = 0.03) and preoperative diagnosis of tumor (OR = 12.3, P = 0.04) were associated with SSI, and S2AI instrumentation (OR = 0.09, P < 0.001) was protective of SSI. CONCLUSION: The use of the S2AI technique over the IS technique was an independent predictor of preventing reoperation and SSI, while achieving similar clinical and functional outcomes. LEVEL OF EVIDENCE: 4. PMID- 27254658 TI - Frequency and Risk Factors for Additional Lesions in the Axial Spine in Subjects With Chordoma: Indications for Screening. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: We aim to evaluate the frequency and clinical significance of additional lesions in the axial spine in subjects with chordoma and to assess the need for screening. SUMMARY OF BACKGROUND DATA: Chordomas are rare tumors that may be multicentric or metastasize and affect several bones in the axial spine. The incidence of multiple lesions in the axial spine is unknown. Understanding the incidence rate of multiple lesions in the spine in subjects with chordomas will help guide utilization of total spine screening imaging. METHODS: We performed a retrospective review of medical records of 42 subjects with histologically confirmed chordomas who had complete imaging of the axial spine. Lesions with imaging characteristics suggestive of chordomas/notochordal remnants were identified. Data on age at diagnosis, sex, size (in maximal dimension), type of chordoma (conventional, chondroid, or dedifferentiated), and whether pulmonary metastases were present were recorded. Binomial two-sample tests of proportions were used to compare proportions. Logistic regression was used to assess predictors of additional lesions. RESULTS: Forty-two subjects (57.1% male) were identified. The proportion of subjects with additional lesions in the axial spine was 16.7% (7/42). Age, sex, size, and subtype of chordoma were not significant predictors of having additional lesions (P > 0.05 for each variable). However, having pulmonary metastases was a significant predictor of having additional lesions (P < 0.05). CONCLUSION: Approximately 17% of subjects with chordomas had additional lesions in the axial spine. It is unclear whether these represent metastases, synchronous primary chordomas or notochordal remnant tissue. Screening imaging of the axial spine may reveal additional lesions in particular in subjects with pulmonary metastases. LEVEL OF EVIDENCE: 3. PMID- 27254659 TI - Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats. AB - Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID- 27254660 TI - Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide. AB - In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61%) vs 23 (39%) males, and of whites, 49 (83.1%) vs 10 (16.9%) blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6). Regarding staging at diagnosis, 27 (45.7%) patients were in stage III A, with 12 (20.3%) patients having serum creatinine >=2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40) were: neutropenia (42.5%), diarrhea (47.5%), and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26) and sc (n=14) administration routes (P=0.343). In the group treated with thalidomide (n=19), 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038). Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%). Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines. PMID- 27254661 TI - Long-term efficacy of endovascular vs open surgical repair for complicated type-B aortic dissection: a single-center retrospective study and meta-analysis. AB - This study aimed to evaluate the long-term survival and risk factors of traditional open surgical repair (OSR) vs thoracic endovascular aneurysm repair (TEVAR) for complicated type-B aortic dissection (TBAD). A total of 118 inpatients (45 OSR vs 73 TEVAR) with TBAD were enrolled from January 2004 to January 2015. Kaplan-Meier curves and Cox proportional hazards analysis were performed to identify the long-term survival rate and independent predictors of survival, respectively. Meta-analysis was used to further explore the long-term efficacy of OSR and TEVAR in the eight included studies using Review Manager 5.2 software. An overall 10-year survival rate of 41.9% was found, and it was similar in the two groups (56.7% OSR vs 26.1% TEVAR; log-rank P=0.953). The risk factors of long-term survival were refractory hypertension (OR=11.1; 95%CI=1.428-86.372; P=0.021] and preoperative aortic diameter >55 mm (OR=4.5; 95%CI=1.842-11.346; P=0.001). Long-term survival rate did not differ significantly between OSR and TEVAR (hazard ratio=0.87; 95%CI=0.52-1.47; P=0.61). Compared with OSR, TEVAR did not show long-term advantages for patients with TBAD. Refractory hypertension and total aortic diameter >55 mm can be used to predict the long-term survival of TBAD in the Chinese Han population. PMID- 27254662 TI - Prevalence of genital human papillomavirus among rural and urban populations in southern Yunnan province, China. AB - This study was designed to investigate and compare the HPV prevalence, genotypes distribution and associated risk factors in rural and urban women living in Xishuang Banna district, in the province of Yunnan. A total of 177 and 190 women from rural and urban areas were engaged, respectively. HPV DNA was amplified using the L1 consensus primers system (MY09/11 and GP5/6) and HPV GenoArray test was conducted for genotyping. Proportions were compared by chi-square test, and logistic regression was used to evaluate risk factors. A total of 54 women were positive for HPV DNA. Among rural women, 23 women were positive for HPV infection, of which 21 showed a single infection and 2 had a multiple infection. HPV-16 (10/23) was the most prevalent genotype followed by HPV-52 (5/23), and HPV 58 (5/23). Urban women had a higher infection rate for overall HPV (31/54) and for multiple genotype infection (8/31). HPV-52 (9/31) was the most prevalent genotype followed by HPV-39 (7/31) and HPV-68 (5/31). The age-specific HPV prevalence was also different between rural and urban women. In urban area, women with age <35 years had the highest HPV prevalence, which declined thereafter as age advanced. However, in rural women the highest HPV prevalence was observed in an older age group (>56 years). Ethnicity, smoking and parity were significantly associated with HPV infection among urban women. Our study demonstrates that HPV prevalence and genotype distribution varies among women from rural and urban areas in the south of Yunnan. PMID- 27254663 TI - Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-beta1 improves cardiac function in heart failure rats. AB - The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-beta1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-beta1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-beta1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF beta1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-beta1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, alpha-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while alpha-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-beta1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-beta1 improved cardiac function in heart failure rats. PMID- 27254665 TI - Surgical Outcomes of Synchronous Multiple Primary Non-Small Cell Lung Cancers. AB - The prognostic indicators for synchronous multiple primary non-small cell lung cancer (NSCLC) vary across reports. In present study, the prognostic factors for the patients with synchronous multiple primary NSCLC were analyzed in a large cohort. A total of 285 patients with synchronous multiple primary NSCLC who underwent radical surgical resection and with complete follow-up information were included in this study. The Kaplan-Meier method were used for survival analysis, Cox proportional hazards regression models were used for risk factors evaluation. Among them, 94 (33.0%) patients had bilateral tumors and 51 (17.9%) had multiple (>=3) tumors. The 5-year disease-free survival (DFS) and overall survival (OS) rate was 58.7% and 77.6%, respectively. Univariate analysis identified parameters conferring shorter OS including male gender, symptomatic disease, negative family history, large maximal tumor size, not all adenocarcinomas, advanced highest T stage, and lymph node involvement. Multivariate analysis showed that male gender (p = 0.020), symptomatic disease (p = 0.017), and lymph node involvement (p < 0.001) were independent adverse prognosticators. For patients with multiple adenocarcinomas, the 5-year DFS and OS rate was 59.6% and 82.4%, respectively. The subtypes other than lepidic predominant (p < 0.001) and lymph node involvement (p = 0.002) were the independent unfavorable prognosticators. In conclusion, we identified independent prognosticators which will provide the valuable clues for postoperative management of patients with synchronous multiple primary NSCLC. PMID- 27254666 TI - Photo-reduction of CO2 Using a Rhenium Complex Covalently Supported on a Graphene/TiO2 Composite. AB - One of the promising solutions for decreasing atmospheric CO2 is artificial photosynthesis, in which CO2 can be photoconverted into solar fuels. In this study, a rhenium complex Re(PyBn)(CO)3 Cl (PyBn=1-(2-picolyl)-4-phenyl-1H-1,2,3 triazole) was covalently grafted onto the surface of reduced graphene oxide (rGO). This was further combined with TiO2 to fabricate a novel catalyst composite TiO2 -rGO-Re(PyBn)(CO)3 Cl for CO2 photo-reduction. This hybrid composite demonstrated high selectivity conversion of CO2 into CO under xenon lamp irradiation. Compared with the unsupported homogeneous catalyst Re(PyBn)(CO)3 Cl, the covalent immobilized catalyst composite TiO2 -rGO Re(PyBn)(CO)3 Cl enhanced the turnover number six times and significantly improved catalyst stability. During the process of CO2 photo-reduction, intermediate species with lifetimes longer than hundreds of microseconds were observed and the formation of CO products was revealed using timeresolved infrared spectroscopy. A plausible mechanism for CO2 photo-reduction by the TiO2 rGO-Re(PyBn)(CO)3 Cl catalyst composite has been suggested. The obtained results have implications for the future design of efficient catalyst composites for CO2 photo-conversion. PMID- 27254667 TI - Cavitands as Reaction Vessels and Blocking Groups for Selective Reactions in Water. AB - The majority of reactions currently performed in the chemical industry take place in organic solvents, compounds that are generally derived from petrochemicals. To promote chemical processes in water, we examined the use of synthetic, deep water soluble cavitands in the Staudinger reduction of long-chain aliphatic diazides (C8 , C10 , and C12 ). The diazide substrates are taken up by the cavitand in D2 O in folded, dynamic conformations. The reduction of one azide group to an amine gives a complex in which the substrate is fixed in an unsymmetrical conformation, with the amine terminal exposed and the azide terminal deep and inaccessible within the cavitand. Accordingly, the reduction of the second azide group is inhibited, even with excess phosphine, and good yields of the monofunctionalized products are obtained. In contrast, the reduction of the free diazides in bulk solution yields diamine products. PMID- 27254664 TI - NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies. AB - Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is neuroprotective in numerous preclinical models of neurodegeneration. Here, we show that brain nmnat2 mRNA levels correlate positively with global cognitive function and negatively with AD pathology. In AD brains, NMNAT2 mRNA and protein levels are reduced. NMNAT2 shifts its solubility and colocalizes with aggregated Tau in AD brains, similar to chaperones, which aid in the clearance or refolding of misfolded proteins. Investigating the mechanism of this observation, we discover a novel chaperone function of NMNAT2, independent from its enzymatic activity. NMNAT2 complexes with heat shock protein 90 (HSP90) to refold aggregated protein substrates. NMNAT2's refoldase activity requires a unique C-terminal ATP site, activated in the presence of HSP90. Furthermore, deleting NMNAT2 function increases the vulnerability of cortical neurons to proteotoxic stress and excitotoxicity. Interestingly, NMNAT2 acts as a chaperone to reduce proteotoxic stress, while its enzymatic activity protects neurons from excitotoxicity. Taken together, our data indicate that NMNAT2 exerts its chaperone or enzymatic function in a context-dependent manner to maintain neuronal health. PMID- 27254668 TI - Evolution-Based Functional Decomposition of Proteins. AB - The essential biological properties of proteins-folding, biochemical activities, and the capacity to adapt-arise from the global pattern of interactions between amino acid residues. The statistical coupling analysis (SCA) is an approach to defining this pattern that involves the study of amino acid coevolution in an ensemble of sequences comprising a protein family. This approach indicates a functional architecture within proteins in which the basic units are coupled networks of amino acids termed sectors. This evolution-based decomposition has potential for new understandings of the structural basis for protein function. To facilitate its usage, we present here the principles and practice of the SCA and introduce new methods for sector analysis in a python-based software package (pySCA). We show that the pattern of amino acid interactions within sectors is linked to the divergence of functional lineages in a multiple sequence alignment a model for how sector properties might be differentially tuned in members of a protein family. This work provides new tools for studying proteins and for generally testing the concept of sectors as the principal units of function and adaptive variation. PMID- 27254725 TI - Priorities for Improving Hearing Health Care for Adults: A Report From the National Academies of Sciences, Engineering, and Medicine. PMID- 27254726 TI - How Different Molecular Architectures Influence the Dynamics of H-Bonded Structures in Glass-Forming Monohydroxy Alcohols. AB - Primary alcohols have been an active area of research since the beginning of the 20th century. The main problem in studying monohydroxy alcohols is the molecular origin of the slower Debye relaxation, whereas the faster process, recognized as structural relaxation, remains much less investigated. This is because in many primary alcohols the structural process is strongly overlapped by the dominating Debye relaxation. Additionally, there is still no answer for many fundamental questions concerning the origin of the molecular characteristic properties of these materials. One of them is the role of molecular architecture in the formation of hydrogen-bonded structures and its potential connection to the relaxation dynamics of Debye and structural relaxation processes. In this article, we present the results of ambient and high-pressure dielectric studies of monohydroxy alcohols with similar chemical structures but different carbon chain lengths (2-ethyl-1-butanol and 2-ethyl-1-hexanol) and positions of the OH- group (2-methyl-2-hexanol and 2-methyl-3-hexanol). New data are compared with previously collected results for 5-methyl-2-hexanol. We note that differences in molecular architecture have a significant influence on the formation of hydrogen bonded structures, which is reflected in the behavior of the Debye and structural relaxation processes. Intriguingly, studying the relaxation dynamics in monohydroxy alcohols at high pressures of up to p = 1700 MPa delivers a fundamental bridge to understand the potential connection between molecular conformation and its response to the characteristic properties of these materials. PMID- 27254727 TI - Efficient Ceria-Platinum Inverse Catalyst for Partial Oxidation of Methanol. AB - Ceria-platinum-based bilayered thin films deposited by magnetron sputtering were developed and tested in regard to their catalytic activity for methanol oxidation by employing a temperature-programmed reaction (TPR) technique. The composition and structure of the samples were characterized by X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Both conventional (oxide-supported metal nanoparticles [NPs]) and inverse configurations (metal with oxide overlayer) were analyzed to uncover the structural dependence of activity and selectivity of these catalysts with respect to different pathways of methanol oxidation. We clearly demonstrate that the amount of cerium oxide (ceria) loading has a profound influence on methanol oxidation reaction characteristics. Adding a noncontinuous adlayer of ceria greatly enhances the catalytic performance of platinum (Pt) in favor of partial oxidation of methanol (POM), gaining an order of magnitude in the absolute yield of hydrogen. Moreover, the undesired by-production of carbon monoxide (CO) is strongly suppressed, making the ceria-platinum inverse catalyst a great candidate for clean hydrogen production. It is suggested that the methanol oxidation process is facilitated by the synergistic effect between both components of the inverse catalyst (involving oxygen from ceria and providing a reaction site on the adjacent Pt surface) as well as by the fact that the ability of ceria to exchange oxygen (i.e., to alter the oxidation state of Ce between 3+ and 4+) during the reaction is inversely proportional to its thickness. The increased redox capability of the discontinuous ceria adlayer shifts the preferred reaction pathway from dehydrogenation of hydroxymethyl intermediate to CO in favor of its oxidation to formate. PMID- 27254728 TI - Origin of Spectral Features and Acid-Base Properties of 3,7-Dihydroxyflavone and Its Monofunctional Derivatives in the Ground and Excited States. AB - Comprehensive spectral investigations of 3,7-dihydroxyflavone and its two derivatives, which each contain a methyl-blocked hydroxyl group, reveal complex radiation absorption in the 300-450 nm range and emission in the 370-650 nm range. The absorption and fluorescence characteristics of these compounds depend on the pH/H0 of the water/methanol media, which is caused by the existence of the compounds in various protolytic (cationic, neutral, anionic) and tautomeric forms. Combined analysis of steady-state, time-dependent and fluorescence decay spectral data enabled the identification of the emitting species, determination of their lifetimes with respect to radiative and nonradiative deactivation processes, fluorescence quantum yields, protolytic and tautomeric abilities under various conditions, and acidic dissociation constants of the cationic, neutral, and anionic forms of the compounds. Results of calculations carried out at the DFT and TD DFT levels of theory generally confirmed the experimental findings concerning tautomeric/protolytic transformations and equilibria. Computational methods also provided insight into possible tautomerization pathways. Electronically excited molecules are generally much more susceptible to tautomerization and acidic dissociation than ground-state ones. 3,7 Dihydroxyflavone exhibits distinguishable features among the compounds investigated and can be considered as potential spectral indicator of properties (polarity, hydrophobicity, hydrogen-bonding ability) and acidity/basicity of liquid environments. PMID- 27254729 TI - Autochthonous dengue outbreak in Nimes, South of France, July to September 2015. AB - In August and September 2015, seven locally acquired cases of dengue virus type 1 (DENV-1) were detected in Nimes, south of France, where Aedes albopictus has been established since 2011. Epidemiological and entomological investigations allowed to steer vector control measures to contain transmission. An imported case from French Polynesia with onset fever on 4 July was identified as primary case. This outbreak occurred from 8 August to 11 September in a 300 m radius area. Six sprayings to control mosquitos were performed in the affected area. We describe the first considerable dengue outbreak in mainland France where only sporadic cases of autochthonous dengue were recorded previously (2010, 2013 and 2014). The 69 day-period between the primary case and the last autochthonous case suggests multiple episodes of mosquito infections. The absence of notification of autochthonous cases during the month following the primary case's symptoms onset could be explained by the occurrence of inapparent illness. Recurrence of cases every year since 2013, the size of the 2015 outbreak and continuing expansion of areas with presence of Ae. albopictus highlight the threat of arboviral diseases in parts of Europe. Thus, European guidelines should be assessed and adjusted to the current context. PMID- 27254730 TI - Tough and Thermosensitive Poly(N-isopropylacrylamide)/Graphene Oxide Hydrogels with Macroscopically Oriented Liquid Crystalline Structures. AB - Bulk graphene oxide (GO) nanocomposite materials with macroscopically oriented GO liquid crystalline (LC) structures exhibit interesting anisotropic properties, but their facile preparations remain challenging. This work reports for the first time the facile preparation of poly(N-isopropylacrylamide) (PNIPAM)/GO nanocomposite hydrogels with macroscopically oriented LC structures with the assistance of a flow field induced by vacuum degassing and the in situ polymerization accelerated by GO. The hydrogel prepared with a GO concentration of 5.0 mg mL(-1) exhibits macroscopically aligned LC structures, which endow the gels with anisotropic optical, mechanical properties, and dimensional changes during the phase transition. The hydrogels show dramatically enhanced tensile mechanical properties and phase transition rates. The oriented LC structures are not damaged during the phase transition of the PNIPAM/GO hydrogels, and hence their LC behavior undergoes reversible change. Moreover, highly oriented LC structures can also be formed when the gels are elongated, even for the gels which do not have macroscopically oriented LC structures. Very impressively, the oriented LC structures in the hydrogels can be permanently maintained by drying the gel samples elongated to and then kept at a constant tensile strain. The thermosensitive nature of PNIPAM and the angle-dependent nature of the macroscopically aligned GO LC structures allow the practical applications of the PNIPAM/GO hydrogels as optical switches, soft sensors, and actuators and so on. PMID- 27254731 TI - Principal components analysis and the reported low intrinsic dimensionality of gene expression microarray data. AB - Principal components analysis (PCA) is a common unsupervised method for the analysis of gene expression microarray data, providing information on the overall structure of the analyzed dataset. In the recent years, it has been applied to very large datasets involving many different tissues and cell types, in order to create a low dimensional global map of human gene expression. Here, we reevaluate this approach and show that the linear intrinsic dimensionality of this global map is higher than previously reported. Furthermore, we analyze in which cases PCA fails to detect biologically relevant information and point the reader to methods that overcome these limitations. Our results refine the current understanding of the overall structure of gene expression spaces and show that PCA critically depends on the effect size of the biological signal as well as on the fraction of samples containing this signal. PMID- 27254732 TI - Chirality and catalysis with aromatic N-fused heterobicyclic carbenes. AB - The benzoannulation of the most common families of aromatic NHCs, imidazol-2 ylidenes and 1,2,4-triazol-3-ylidenes, results in heterobicyclic imidazo[1,5 a]pyridin-3-ylidenes ('s) and [1,2,4]triazolo[4,3-a]pyridin-3-ylidenes ('s), characterized by a bridged N atom. These are versatile platforms that offer multiple possibilities for the modulation of the steric and electronic properties of the carbene ligand and/or organocatalyst, and offer also diverse opportunities for the introduction of several types of chiralities. In this paper the different families of chiral and carbenes and their application in asymmetric catalysis will be discussed. PMID- 27254744 TI - Simulations of Pore Formation in Lipid Membranes: Reaction Coordinates, Convergence, Hysteresis, and Finite-Size Effects. AB - Transmembrane pores play an important role in various biophysical processes such as membrane permeation, membrane fusion, and antimicrobial peptide activity. In principal, all-atom molecular dynamics (MD) simulations provide an accurate model of pore formation in lipid membranes. However, the free energy landscape of transmembrane pore formation remains poorly understood, partly because potential of mean force (PMF) calculations of pore formation strongly depend on the choice of the reaction coordinate. In this study, we used umbrella sampling to compute PMFs for pore formation using three different reaction coordinates, namely, (i) a coordinate that steers the lipids in the lateral direction away from the pore center, (ii) the distance of a single lipid phosphate group from the membrane center, and (iii) the average water density inside a membrane-spanning cylinder. Our results show that while the three reaction coordinates efficiently form pores in membranes, they suffer from strong hysteresis between pore-opening and pore closing simulations, suggesting that they do not restrain the systems close to the transition state for pore formation. The two reaction coordinates that act via restraining the lipids lead to more pronounced hysteresis compared with the coordinate acting on the water molecules. By comparing PMFs computed from membranes with different numbers of lipids, we observed significant artifacts from the periodic boundary conditions in small simulation systems. Further analysis suggests that the formation and disruption of a continuous hydrogen bonding network across the membrane corresponds to the transition state for pore formation. Our study provides molecular insights into the critical steps of transmembrane pore formation, and it may guide the development of efficient reaction coordinates for pore formation. PMID- 27254743 TI - Effects of supplemental calcium and vitamin D on the APC/beta-catenin pathway in the normal colorectal mucosa of colorectal adenoma patients. AB - APC/beta-catenin pathway malfunction is a common and early event in colorectal carcinogenesis. To assess calcium and vitamin D effects on the APC/beta-catenin pathway in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, nested within a larger randomized, double-blind, placebo-controlled, partial 2 * 2 factorial chemoprevention clinical trial of supplemental calcium (1200 mg daily) and vitamin D (1000 IU daily), alone and in combination versus placebo, we assessed APC, beta-catenin, and E-cadherin expression in colon crypts in normal-appearing rectal mucosa biopsies from 104 participants at baseline and 1-yr follow up using standardized, automated immunohistochemistry and quantitative image analysis. For vitamin D versus no vitamin D, the ratio of APC expression to beta-catenin expression in the upper 40% (differentiation zone) of crypts (APC/beta-catenin score) increased by 28% (P = 0.02), for calcium versus no calcium it increased by 1% (P = 0.88), and for vitamin D + calcium versus calcium by 35% (P = 0.01). Total E-cadherin expression increased by 7% (P = 0.35) for vitamin D versus no vitamin D, 8% (P = 0.31) for calcium versus no calcium, and 12% (P = 0.21) for vitamin D + calcium versus calcium. These results support (i) that vitamin D, alone or in combination with calcium, may modify APC, beta catenin, and E-cadherin expression in humans in directions hypothesized to reduce risk for colorectal neoplasms; (ii) vitamin D as a potential chemopreventive agent against colorectal neoplasms; and (iii) the potential of APC, beta-catenin, and E-cadherin expression as treatable, pre-neoplastic risk biomarkers for colorectal neoplasms. (c) 2016 Wiley Periodicals, Inc. PMID- 27254745 TI - The bivalve Glycymeris pilosa as a multidecadal environmental archive for the Adriatic and Mediterranean Seas. AB - We evaluated the potential of Glycymeris pilosa as an environmental indicator for the Mediterranean region by applying sclerochronological techniques on a sample set collected from Pasman Channel in the middle Adriatic Sea. Maximal longevity of analyzed shells was 69 years. Growth increments in acetate peels of the hinge region had clear boundaries, and there was a strongly synchronous signal in growth-increment width among individuals. The final, replicated chronology spanned 1969 to 2013. Shell growth negatively correlated with local summer sea temperatures and positively with November precipitation. High correlation between shell growth and circulation patterns in the northern Ionian was also observed, with slower growth occurring during cyclonic regimes. Given its broad distribution in the region and the ability to crossdate, generate annually resolved chronologies, and of a length that substantially overlaps with observational records, G. pilosa has considerable potential to test hypotheses relating to environmental variability and biological response in the Mediterranean. PMID- 27254746 TI - Activity and MeCP2-dependent regulation of nNOS levels in enteric neurons. AB - BACKGROUND: Rett syndrome (RTT) is a neurological disorder characterized by severe cognitive impairment, motor dyspraxia, and seizures. Rett syndrome arises predominantly from mutations in MECP2, the gene coding for methyl-CpG-binding protein 2 (MeCP2). MeCP2 is an important mediator of synaptic development and is essential in regulating homeostatic synaptic plasticity (HSP) in the brain. In addition to demonstrating central nervous system impairment, RTT patients also suffer from gastrointestinal (GI) dysmotility. We hypothesize that this is due to a similar impairment of plasticity-dependent synaptic function in the enteric nervous system (ENS). We recently reported that MeCP2 is expressed in the ENS, providing evidence that neuronal dysfunction may mediate the GI pathology. METHODS: Baseline measures of MeCP2-KO vs wild-type (WT) GI neuronal nitric oxide synthase (nNOS) were assessed in tissue samples and in vitro. Experiments were carried out to measure nNOS in baseline vs activated plasticity states in vitro. Functional in vivo studies were carried out to determine whether MeCP2-KO mice reproduced the RTT GI hypomotility. KEY RESULTS: Methyl-CpG-binding protein 2-KO mice reproduced the GI hypomotility seen in RTT. MeCP2-KO GI tissue demonstrated elevated nNOS levels. Cultured WT enteric neurons showed upregulation of nNOS following moderate, prolonged stimulation by hyperkalemia; neurons from MeCP2-KO mice failed to show this nNOS upregulation. CONCLUSIONS & INFERENCES: MeCP2 is required for proper GI motility and normal nNOS levels. Neuronal nitric oxide synthase imbalances could mediate the GI dysmotility seen in RTT. Disruption of MeCP2-dependent HSP may be the basis for aberrant nNOS levels and hence GI dysmotility in MeCP2-KO and RTT. PMID- 27254747 TI - Mortality and survival patterns of people living with HIV-2. AB - PURPOSE OF REVIEW: People living with HIV-2 infected usually initiate antiretroviral therapy (ART) at an advanced period in the course of their infection after a long asymptomatic period characterized by high CD4 cell count and thus at a relatively advanced age. In the new international context of early and universal ART initiation, the aim was to review survival patterns among HIV-2 infected patients, either on ART or not. RECENT FINDINGS: Very few reports were published on mortality in people living with HIV-2 during the last 5 years. People living with HIV-2 experience high mortality rates although lower than people living with HIV-1 before ART initiation. They seem to survive longer regardless of the conditions of ART use. Mortality is associated with late presentation, male sex, CD4 cell count less than 500 cell/MUl, high plasma viral load, hemoglobin rate less than 8 g/dl and body mass index less than 18 kg/m. SUMMARY: People living with HIV-2 initiate ART later than HIV-1 and HIV duals, resulting in higher disease progression and mortality rate. The clinical management of HIV-2 infected patients should now include early diagnosis and treatment initiation as per international guidelines. Further research needs to explore the 'what to start' question and document specific causes of death in people living with HIV-2 and enrolled in care in Africa. PMID- 27254748 TI - Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. AB - PURPOSE OF REVIEW: Improved virological and immunological outcomes and reduced toxicity of antiretroviral combination therapy (ART) raise the hope that life expectancy of HIV-positive persons on ART will approach that of the general population. We systematically review the literature and summarize published estimates of life expectancy of HIV-positive populations on ART. We compare their life expectancy with the life expectancy of the general or, in sub-Saharan Africa, HIV-negative populations, by time period and gender. RECENT FINDINGS: Ten relevant studies were published from 2006 to 2015. Three studies were from Canada, two from European countries, three from sub-Saharan Africa and two were multicountry studies. Life expectancy increased over time in all studies and regions. Expressed as the percentage of life expectancy in the HIV-negative or general population, estimated life expectancy at age 20 years in HIV-positive people on ART ranged from 60.3% (95% CI 58.0-62.6%) in Rwanda (2008-2011) to 89.1% (95% CI 84.7-93.6%) in Canada (2008-2012). The percentage of life expectancy in the HIV-negative or general population achieved was higher in HIV positive women than in HIV-positive men in all countries, except for Canada wherein the opposite was the case. SUMMARY: Life expectancy in HIV-positive people on ART has improved worldwide in recent years, but important gaps remain compared with the general and HIV-negative population, and between regions and genders. PMID- 27254750 TI - Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer. AB - Importance: The role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain. Objective: To establish the safety and efficacy of upfront pazopanib therapy prior to cytoreductive nephrectomy in previously untreated patients with metastatic clear cell renal cancer. Design, Setting, and Participants: Single-arm phase 2 study of 104 previously untreated patients with metastatic clear cell renal cancer recruited between June 2008 and October 2012 at cancer treatment centers with access to nephrectomy services. The minimum follow-up was 30 months. Interventions: Patients received 12 to 14 weeks of preoperative pazopanib therapy prior to planned cytoreductive nephrectomy and continued pazopanib therapy after surgery. Treatment was stopped at disease progression. Main Outcomes and Measures: The primary end point was clinical benefit (using Response Evaluation Criteria in Solid Tumors, version 1.1) prior to surgery (at 12-14 weeks). Secondary end points included surgical complications, progression-free survival (PFS), overall survival (OS), and biomarker analysis. Results: Of 104 patients recruited, 100 patients were assessable for clinical benefit prior to planned nephrectomy; 80 of 104 (76.9%) were men; median [interquartile range] age, 64 [56-71] years). Overall, 84 of 100 (84% [95% CI, 75%-91%]) gained clinical benefit before planned nephrectomy. The median reduction in the size of the primary tumor was 14.4% (interquartile range, 1.4%-21.1%). No patients were unable to undergo surgery as a result of local progression of disease. Nephrectomy was performed in 63 (61%) of patients; 14 (22%) reported surgical complications. The 2 most common reasons for not undergoing surgery were progression of disease (n = 13) and patient choice (n = 9). There was 1 postoperative surgical death. The median PFS and OS for the whole cohort were 7.1 (95% CI, 6.0-9.2) and 22.7 (95% CI, 14.3-not estimable) months, respectively. Patients with MSKCC poor-risk disease or progressive disease prior to surgery had a poor outcome (median OS, 5.7 [95% CI, 2.6-10.8] and 3.9 [95% CI, 0.5-9.1] months, respectively). Surgical complications were observed in 14 (22%) of the nephrectomies. Biomarker analysis from sequential tissue samples revealed a decrease in CD8 expression (20.00 vs 13.75; P = .05) and significant reduction in expression of von Hippel-Lindau tumor suppressor (100 vs 40; P < .001) and C-MET (300 vs 100; P < .001) and increased programmed cell death ligand 1 expression (0 vs 1.5; P < .001) in the immune component. No on-treatment biomarker correlated with response. Conclusions and Relevance: Nephrectomy after upfront pazopanib therapy could be performed safely and was associated with good outcomes in patients with intermediate-risk metastatic clear cell renal cancer. PMID- 27254749 TI - Reducing rates of preventable HIV/AIDS-associated mortality among people living with HIV who inject drugs. AB - PURPOSE OF REVIEW: The modern antiretroviral therapy (ART) era has seen substantial reductions in mortality among people living with HIV. However, HIV positive people who inject drugs (PWIDs) continue to experience high rates of suboptimal HIV-related outcomes. We review recent findings regarding factors contributing to premature and preventable mortality among HIV-positive PWID, and describe the promise of interventions to improve survival in this group. RECENT FINDINGS: The current leading causes of death among HIV-positive PWID are HIV/AIDS-related causes, overdose, and liver-related causes, including infection with hepatitis C virus. Elevated mortality levels in this population are driven by social-structural barriers to ART access and adherence, particularly criminalization and stigmatization of drug use. In contexts where opioid substitution therapy and ART adherence support programs are widely accessible, evidence highlights comparable levels of survival among HIV-positive PWID and people living with HIV who do not inject drugs. SUMMARY: The life-saving benefits of ART can be realized among HIV-positive PWID when it is paired with strategies that address barriers to evidence-based medical care. Joint administration of ART and opioid substitution therapy, as well as repeal of punitive laws that criminalize drug users, are urgently needed to reduce HIV and injection-related mortality among PWID. PMID- 27254751 TI - Design of an enzyme cocktail consisting of different fungal platforms for efficient hydrolysis of sugarcane bagasse: Optimization and synergism studies. AB - Lignocellulosic materials represent a very important and promising source of renewable biomass. In order to turn them into fermentable sugars, synergism among the different enzymes that carry out bioconversion of these materials is one of the main factors that should be considered. Experimental mixture design was performed to optimize the proportion of enzymes produced by native strains of Trichoderma harzianum IOC 3844, Penicillium funiculosum ATCC 11797, and Aspergillus niger ATCC 1004, resulting in a proportion of 15, 50, and 35%, respectively. This mixture was able to hydrolyze 25 g/L of pretreated sugarcane bagasse with 91% of yield after 48 h of enzymatic reaction. Synergism along the hydrolysis process, besides the influence of lignin, hemicellulose, and solids loading, were also studied. Response surface methodology (RSM) based on Central Composite Rotatable Design was used to optimize solids and protein loadings to increase glucose release and enzymatic hydrolysis yield. The optimum solid and protein loadings established with RSM were 196 g/L and 24 mg/g cellulose, respectively, and under these conditions (94.1 +/- 8) g/L of glucose were obtained, corresponding to a hydrolysis yield of 64%. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1222-1229, 2016. PMID- 27254752 TI - Easy and Fast Western Blotting by Thin-Film Direct Coating with Suction. AB - Thin-film direct coating (TDC) has been successfully used in Western blotting (WB). In this study, the advanced technique of TDC with suction (TDCS) was developed to reduce the consumption amount of antibody by a factor of up to 10(4) in comparison with the amount consumed by the conventional WB using the capillary tube without any need of special micromachining processes. The operation time for completely finishing a high-quality WB can be reduced from 3 h in conventional WB to about 5 min or even less by TDCS. In addition, the signal-to-noise ratio of the immunoblotting by TDCS can be markedly increased. TDCS WB showed a high linearity within a 6-log2 dynamic range for detecting 90-6000 ng of purified recombinant glutathione-S-transferase (GST) proteins and could particularly detect extrinsic GST proteins added in crude Escherichia coli or 293T cell lysates. Moreover, a protein mixture containing bovine serum albumin, GST, and ubiquitin could be specifically probed in parallel with their corresponding antibodies through multichannel TDCS WB. This simple and innovative TDCS WB offers various potential applications in simultaneously finishing multiple antibody-antigen screenings in a fast and single experiment. PMID- 27254753 TI - CRSI Bronze Medals: P. S. Mukherjee, D. B. Ramachary, T. Govindaraju, and R. Gupta / SwarnaJayanti Fellowships: S. Ghosh and C. M. Reddy / Albrecht Kossel Prize: J. Buchner / DECHEMA Early-Career Researcher Prize: T. A. M. Gulder / Mattauch-Herzog Prize: K. Pagel / Honorary Doctorates: F. Schuth and T. J. Marks / Karl Max von Bauernfeind Medal: C. W. Kohlpaintner. PMID- 27254754 TI - Dopamine pathway imbalance in mice lacking Magel2, a Prader-Willi syndrome candidate gene. AB - The etiology of abnormal eating behaviors, including binge-eating disorder, is poorly understood. The neural circuits modulating the activities of the neurotransmitters dopamine and serotonin are proposed to be dysfunctional in individuals suffering from eating disorders. Prader-Willi syndrome is a neurodevelopmental disorder that causes extreme food seeking and binge-eating behaviors together with reduced satiety. One of the genes implicated in Prader Willi syndrome, Magel2, is highly expressed in the regions of the brain that control appetite. Our objective was to examine behaviors relevant to feeding and the neural circuits controlling feeding in a mouse model of Prader-Willi syndrome that lacks expression of the Magel2 gene. We performed behavioral tests related to dopaminergic function, measuring cocaine-induced hyperlocomotion, binge eating, and saccharin-induced anhedonia in Magel2-deficient mice. Next, we analyzed dopaminergic neurons in various brain regions and compared these findings between genotypes. Finally, we examined biochemical markers in the brain under standard diet, high-fat diet, and withdrawal from a high-fat diet conditions. We identified abnormal behaviors and biomarkers reflecting dopaminergic dysfunction in mice lacking Magel2. Our results provide a biological framework for clinical studies of dopaminergic function in children with Prader Willi syndrome, and may also provide insight into binge-eating disorders that occur in the general population. (PsycINFO Database Record PMID- 27254755 TI - Wire-guided intraduodenal ultrasonography using a catheter probe in the differential diagnosis of enlarged ampullary lesions. AB - BACKGROUND AND AIM: It can be difficult to identify the cause of an enlarged ampulla of Vater (AOV). This study evaluated the accuracy of wire-guided intraduodenal ultrasonography (US) for the differential diagnosis of an enlarged AOV during endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: Thirty-four patients with enlarged AOVs of unknown cause identified on imaging studies or endoscopic observations underwent wire-guided intraduodenal US using a catheter probe. RESULTS: The final diagnoses were malignant or premalignant tumors in 10 patients (29.4%), stones in nine patients (26.5%), inflammation in 14 patients (41.2%), and cyst in one patient (2.9%). The overall diagnostic accuracy of intraduodenal US for enlarged AOVs was 91.2%. The diagnostic accuracies of stones, inflammation, and AOV tumors were 100.0%, 94.1%, and 91.1%, respectively. CONCLUSIONS: Wire-guided intraduodenal US using a catheter probe is readily applicable during ERCP and may be useful in the differential diagnosis of enlarged ampullary lesions. PMID- 27254756 TI - Parathyroid Hormone Replacement Therapy in Hypoparathyroidism: A Meta-Analysis. AB - This study investigated the effect of human parathyroid hormone replacement therapy on specific disease-related outcomes in patients with hypoparathyroidism. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until January 13, 2015 for randomized trials using the following search terms: hypoparathyroidism, parathyroid hormone/PTH, and hormone replacement therapy. Five randomized controlled trials (n=245) that investigated effect of either PTH (1-34) (3 trials) or PTH (1-84) (2 trials) on serum calcium, phosphate, 1, 25 dihydroxyvitamin D, 25-dihydroxyvitamin D levels, and urine level of calcium were included in the meta-analysis. Both PTH (1-34) and PTH (1-84) therapies were not associated with change in serum calcium level compared with calcitriol/placebo. The level of 24-h urine calcium excretion had a significant decrease in PTH (1 34)-treated group compared placebo/calcitriol (control) group (p<=0.012). PTH (1 34) did not change serum phosphate (p=0.053). PTH (1-84) did not change level of 24-h urine calcium excretion compared with control (p>=0.214) but it did decrease the levels of serum phosphorous (p=0.000). Both PTH-replacement therapies were not associated with change in serum 1,25-dihydroxyvitamin D level compared with control (p>=0.606), but were associated with a significant decrease in serum 25 dihydroxyvitamin D levels (p<=0.04). In conclusion, although the number of randomized trial is limited, our meta-analysis suggests that PTH (1-34) replacement therapy may maintain the serum calcium levels in the normal range by reducing the levels of urine calcium excretion, and both replacement therapies may maintain 1,25-dihydroxyvitamin D serum levels by reducing serum level of 25 dihydroxyvitamin D. PMID- 27254757 TI - Characterization of extracellular polymeric substances of Bacillus amyloliquefaciens SQR9 induced by root exudates of cucumber. AB - Bacillus amyloliquefaciens SQR9 is a plant growth-promoting rhizobacterium (PGPRs) that forms biofilm on the roots of plants and protects them from a variety of pathogens. In this study, we reported the effect of root exudates produced by cucumber (Cucumis sativus L.) at different developmental stages on the biochemical composition of the biofilm matrix of SQR9. The results showed that the amino acids present in the root exudates of cucumber were responsible for triggering biofilm formation of SQR9. In addition, when root exudates harvested at different growth phases of cucumber were used as carbon sources for biofilm formation, the resulting biofilm matrixes differed both quantitatively and qualitatively. The biofilm matrix was mostly composed of amino groups observed by confocal laser scanning microscope (CLSM) hence the proteins formed the major component of the resulting extracellular polymeric substances (EPS). The potential use of amino acid-based dietary supplements to control biofilm formation in the plants may be a viable option to improve agricultural productivity by recruiting beneficial association with PGPRs in the manufacture of bio fertilizers or bio controls. PMID- 27254758 TI - Native American men-women, lesbians, two-spirits: Contemporary and historical perspectives. AB - People living in the role of the "other" sex in Native American cultures, often entering into same-sex relationships, have been subject to various anthropological, historical, and psychological analyses and interpretations. Most recently, there has been a shift to an indigenist/decolonial interdisciplinary focus on lesbian, gay, bisexual, transgender, and queer Native people. This article gives a discussion of approaches to the subject, with a focus on female gender variability. An overview is given of the latter, complemented by a discussion of the identities and concerns of contemporary Native lesbians, many of whom identify as "two-spirit," a term that alludes to the dual, spiritually powerful nature traditionally attributed in a number of Native American cultures to individuals who combine the feminine and masculine. PMID- 27254759 TI - Blessed by the Holy People. AB - Men-women and women-men have a long tradition in Dine (Navajo) culture where they were, and sometimes still are, held in high esteem. Their supernatural prototypes figure prominently in parts of the Dine Origin Story. It is in this cosmological worldview and tradition of acceptance that Carrie, a multi-dualistic spirit, grew up to be a female-bodied man supported and respected by his/her family and community. He/she has worked in various professions defined as "masculine" in Dine and Western contexts, such as fire fighter, heavy equipment operator, truck driver, and building contractor. In addition, Carrie is a keeper of Dine traditions, and has also been active educating Native and Non-Native audiences on 2SpiritLesbianGayBiTransIntersexQueer issues. PMID- 27254760 TI - Lesbian landscape. AB - In this article about first love, the author discusses her coming of age as a lesbian who is also tribally affiliated. PMID- 27254761 TI - "I'm in this world for a reason": Resilience and recovery among American Indian and Alaska Native two-spirit women. AB - American Indian and Alaska Native sexual minority (two-spirit) women are vulnerable to substance misuse and mental health challenges due to multiple minority oppressed status and exposure to stress and trauma. Yet, these women find pathways toward healing and wellness. We conducted a qualitative data analysis of interviews derived from a national health study and gained an understanding of 11 two-spirit women's resilience and recovery patterns. Emergent from the data, a braided resiliency framework was developed which elucidates multilayered abilities, processes, and resources involved in their resiliency. We recommend that resilience-promoting strategies be incorporated into substance misuse and mental health interventions. PMID- 27254762 TI - Detecting Two-Spirit erotics: The fiction of Carole laFavor. AB - This article examines the life and novels of Carole laFavor, arguing for her importance to and influence in Two-Spirit studies. Along with being a writer, laFavor was a powerful voice for social justice and Indigenous health sovereignty in Minnesota and the nation. Her two novels, Along the Journey River and Evil Dead Center, which both focus on Anishinaabe lesbian detective protagonist Renee LaRoche, are the first lesbian detective fiction published by a Native author. Renee's embrace of a specifically Two-Spirit erotics anchors her to family and brings her tribal community a powerful healing when she employs her skills to protect her people from instances of racism, abuse, and injustice. This article, then, reads these novels as the first of an emerging genre of texts that claim an overtly Two-Spirit erotic as well as vital precursors to the present embrace of sovereign erotics in Indigenous studies. PMID- 27254763 TI - Ojibwe lesbian visual AIDS: On the Red Road with Carole laFavor, Her Giveaway (1988), and Native LGBTQ2 film history. AB - After a century of suppression across the Silent, Classic, and New Hollywood eras, Native Lesbian/Gay media began to proliferate in the post-AIDS 1980s and into the second millennium. Her Giveaway: A Spiritual Journey with AIDS (1988) is a key tribal health AIDS video that exemplified a new contemporary media combination of visual, erotic, and theological sovereignty. The video's central Red Road narrative by the lesbian, Ojibwe, and AIDS/HIV+ spokesperson Carole laFavor emphasizes Native American traditional healing methods involving the medicine wheel and a reclamation of Native lesbian/gay identity. PMID- 27254764 TI - Ancestors of two-spirits: Historical depictions of Native North American gender crossing women through critical discourse analysis. AB - Letters written by Christian men of European origin during the sixteenth nineteenth centuries contain brief descriptions of gender-crossing individuals among indigenous Americans. Although now considered ethnocentrically biased because of the etic positioning of their authors, these historical sources are invaluable because they offer a glimpse of the ancestors of modern-day two spirits. An application of critical discourse analysis to three depictions of gender-crossing females from the eighteenth and nineteenth centuries demonstrates that such women were favorably portrayed. These results differ dramatically from those obtained from my similar analysis of depictions of gender-crossing males. It also became evident that the three descriptions of gender-crossing women were not based on actual observations, but only on hearsay, which makes their use as primary sources questionable. PMID- 27254765 TI - Female-partnered women conceiving kinship: Does sharing a sperm donor mean we are family? AB - This qualitative study explored how 36 initially female-partnered mothers defined their own, and their children's, relationships with families who share their unknown sperm donor (i.e., "linked" families). Shared genetics among children were sometimes sufficient to describe relationships among linked families as familial, especially from the children's perspectives. Most women described their own relationships with linked families as significant but not necessarily in traditional family terms. Family terms were sometimes seen as undermining ties to siblings and genetically unrelated mothers. As shared experiences have come to define "chosen family," definitions of significant relationships must expand to include those defined by shared genetics alone. PMID- 27254767 TI - The Chloroplast Genome of Euglena mutabilis-Cluster Arrangement, Intron Analysis, and Intrageneric Trends. AB - A comparative analysis of the chloroplast genome of Euglena mutabilis underlined a high diversity in the evolution of plastids in euglenids. Gene clusters in more derived Euglenales increased in complexity with only a few, but remarkable changes in the genus Euglena. Euglena mutabilis differed from other Euglena species in a mirror-inverted arrangement of 12 from 15 identified clusters, making it very likely that the emergence at the base of the genus Euglena, which has been considered a long branch artifact, is truly a probable position. This was corroborated by many similarities in gene arrangement and orientation with Strombomonas and Monomorphina, rendering the genome organization of E. mutabilis in certain clusters as plesiomorphic feature. By RNA analysis exact exon-intron boundaries and the type of the 77 introns identified were mostly determined unambiguously. A detailed intron study of psbC pointed at two important issues: First, the number of introns varied even between species, and no trend from few to many introns could be observed. Second, mat1 was localized in Eutreptiales exclusively in intron 1, and mat2 was not identified. With the emergence of Euglenaceae in most species, a new intron containing mat2 inserted in front of the previous intron 1 and thereby became intron 2 with mat1. PMID- 27254769 TI - Improved optical properties of silica/UV-cured polymer composite films made of hollow silica nanoparticles with a hierarchical structure for light diffuser film applications. AB - This study successfully improved the optical properties of silica/UV-cured polymer composite films made of hollow silica nanoparticles having a hierarchical structure. The particles were synthesized by an inorganic particle method, which involves two steps of sol-gel silica coating around the template and acid dissolution removal of the template. The pH of the acid was varied to achieve different hierarchical structures of the particles. The morphologies and surface properties of the obtained particles were characterized before dispersing in a UV curable acrylate monomer solution to prepare dispersions for fabricating light diffuser films. The optical properties and the light diffusing ability of the fabricated films were studied. The results revealed that the increased pH of the acid provides the particles with a thinner shell, a larger hollow interior and a higher specific surface area. Moreover, the films with these particles exhibit a better light diffusing ability and a higher diffuse transmittance value when compared to those without particles. Therefore, the composite films can be used as light diffuser films, which is an essential part of optical diffusers in the back-light unit of LCDs. In addition, utilizing the hierarchical particles probably reduces the number of back-light units in the LCDs leading to energy savings and subsequently lightweight LCDs. PMID- 27254768 TI - Pro-osteoclastic in vitro effect of Polyethylene-like nanoparticles: Involvement in the pathogenesis of implant aseptic loosening. AB - Polyethylene micro-sized wear particles released from orthopedic implants promote inflammation and osteolysis; however, less is known about the bioactivity of polyethylene nanosized wear particles released from the last generation of polymer-bearing surfaces. We aim to assess the internalization of fluorescent polyethylene-like nanoparticles by both human macrophages and osteoclasts and also, to determine their effects in osteoclastogenesis in vitro. Human macrophages and osteoclasts were incubated with several ratios of fluorescent polyethylene-like nanoparticles between 1 and 72 h, and 4 h, 2, 4, 6, and 9 days, respectively. The internalization of nanoparticles was quantified by flow cytometry and followed by both confocal and video time-lapse microscopy. Osteoclast differentiation and activity was semiquantified by tartrate-resistant acid phosphatase (TRAP) staining, TRAP mRNA relative expression, and pit resorption assay, respectively. Macrophages, osteoclast precursors and mature osteoclasts internalized nanoparticles in a dose- and time-dependent manner and maintained their resorptive activity. In addition, nanoparticles significantly increased the osteoclastogenesis as shown by upregulation of the TRAP expressing cell number. We conclude that polyethylene-like nanosized wear particles promote osteoclast differentiation without alteration of bone resorptive activity of mature osteoclasts and they could be considered as important actors in periprosthetic osteolysis of the last new generation of polymer-bearing surfaces. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2649-2657, 2016. PMID- 27254770 TI - Soil pollution at outdoor shooting ranges: Health effects, bioavailability and best management practices. AB - The total lead (Pb) concentrations of the surface soil, sub surface soil, vegetation and surface waters of outdoor shooting ranges are extremely high and above regulatory limits. Lead is dangerous at high concentrations and can cause a variety of serious health problems. Shooters and range workers are exposed to lead dust and can even take Pb dust home to their families while some animals around the shooting range can ingest the Pb bullets. The toxicity of Pb depends on its bioavailability which has been determined to be influenced greatly by the geochemical properties of each site. The bioavailability of Pb in shooting ranges has been found to be higher than other metal contaminated soils probably because of its very low residual Pb (<1%). Despite being an immobile element in the soil, migration of Pb within shooting ranges and offsite has been reported in literature. Best management practices to reduce mobility of Pb in shooting ranges involve an integrated Pb management program which has been described in the paper. The adoption of the non-toxic "green bullet" which has been developed to replace Pb bullets may reduce or prevent environmental pollution at shooting ranges. However, the contaminated soil resulting from decades of operation of several shooting ranges still needs to be restored to its natural state. PMID- 27254771 TI - Magnetic Trapping of Bacteria at Low Magnetic Fields. AB - A suspension of non-magnetic entities in a ferrofluid is referred to as an inverse ferrofluid. Current research to trap non-magnetic entities in an inverse ferrofluid focuses on using large permanent magnets to generate high magnetic field gradients, which seriously limits Lab-on-a-Chip applications. On the other hand, in this work, trapping of non-magnetic entities, e.g., bacteria in a uniform external magnetic field was studied with a novel chip design. An inverse ferrofluid flows in a channel and a non-magnetic island is placed in the middle of this channel. The magnetic field was distorted by this island due to the magnetic susceptibility difference between this island and the surrounding ferrofluid, resulting in magnetic forces applied on the non-magnetic entities. Both the ferromagnetic particles and the non-magnetic entities, e.g., bacteria were attracted towards the island, and subsequently accumulate in different regions. The alignment of the ferrimagnetic particles and optical transparency of the ferrofluid was greatly enhanced by the bacteria at low applied magnetic fields. This work is applicable to lab-on-a-chip based detection and trapping of non-magnetic entities bacteria and cells. PMID- 27254772 TI - The impact of endohedral atoms on the electronic and optical properties of Au25(SR)18 and Au38(SR)24. AB - An understanding of the rational modification of the optical properties of gold nanoparticles allows us to explore their versatility as molecular-sized materials. We show from theoretical relativistic calculations that such properties can be tuned efficiently by varying the architecture of the central core from endohedral to hollow structures in thiolate-protected clusters derived from two prototypical gold clusters, namely, Au25(SR)18 and Au38(SR)24. Our results estimate the feasible variation of the absorption spectrum driven by the modification of frontier levels due to the removal of the endohedral atom, leading to smaller gaps between occupied and low-lying unoccupied levels. This reveals a characteristic consequence for hollow counterparts given by a red-shift in energy of the optical properties. Hence, the formation of hollow derivatives can be a useful strategy for the fine-tuning of such properties. Future work will extend this observation to larger clusters, and allow gleaning knowledge of the electronic and optical properties in the case of higher order multilayer core nanoparticles. PMID- 27254773 TI - Weight loss experiences and willingness to intervention with pharmacotherapy among obese and very obese Danish people. AB - OBJECTIVES: Obesity is a growing issue with increasing impact on healthcare budgets, yet very little is known about weight loss experiences of people with body mass index (BMI)>=30kg/m(2) and their willingness to try and pay for weight loss interventions (WLI). The objective of this survey was to gather knowledge about weight loss experiences among obese and severely obese people. METHODS: 1,003 Danish people >18 years of age with BMI>=30 who wanted to lose weight completed an online survey. Data included demographics, experience with WLI, awareness of anti-obesity medication (AOM), and willingness to try and pay for WLI including AOM. RESULTS: Respondents had been trying to lose weight for several years (medium [25% percentile;75% percentile]);5.1[2.0;10.3] years (BMI 30-35) and 10.0 [5.0;20.0] (very obese (BMI>35) with co-morbidities (OWC). The desired weight loss was 20.0 [15.0;25.0] kg (BMI 30-35) and 35.0 [28.0;47.5] kg (OWC). Independent of educational level and gender, health concern was the main incentive for weight loss. Several WLI had been tried repeatedly, yet 60% of respondents with BMI 30-35 and 50% of the OWC were unaware of AOM. Among those who had tried AOM, side effects and lack of effectiveness were the main reasons to stop. 50-73% were willing to try AOM dependent on expected weight loss. Willingness to try and pay for new AOM was strongest for the OWC. CONCLUSION: Respondents had made repeated attempts for up to a decade to lose weight, yet remained far from their ideal weight. They had spent a substantial amount of money on WLI, had limited information of AOM, and indicated a desire for increased professional support. PMID- 27254774 TI - ADAMTS5 deficiency protects against non-alcoholic steatohepatitis in obesity. AB - BACKGROUND & AIMS: Increased prevalence of obesity is paralleled by an increase in non-alcoholic steatohepatitis (NASH). We previously found that the expression of ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin type 1 motifs; member 5) is enhanced in expanding adipose tissue. However, no information is available on a potential role in liver pathology. We studied the effect of ADAMTS5 deficiency on NASH in mice. METHODS: Wild-type (Adamts5+/+ ) and deficient (Adamts5-/- ) mice were kept on a standard- or high-fat diet (HFD) for 15 weeks. Alternatively, steatohepatitis was induced with methionine/choline deficient (MCD) diet. RESULTS: HFD feeding resulted in comparable body weights for both genotypes, but Adamts5-/- mice had approximately 40% lower liver weight (P = 0.0004). In the Adamts5-/- mice, the HFD as well as the MCD diet consistently induced less NASH with less fibrosis. The deteriorating effect of ADAMTS5 on the liver during diet-induced obesity may be due, at least in part, to proteolytic cleavage of the matrix components syndecan-1 and versican, thereby enhancing hepatic triglyceride clearance from the circulation. Plasma lipid levels were elevated in obese Adamts5-/- mice. There was no clear effect of ADAMTS5 deficiency on glycaemia or glucose tolerance, whereas insulin sensitivity was somewhat improved. Furthermore, Adamts5-/- mice were protected from hepatic mitochondrial dysfunction, as indicated by increased mitochondrial respiratory chain complex activity, higher ATP levels and higher expression of antioxidant enzymes. CONCLUSIONS: Absence of ADAMTS5 preserves liver integrity in a diet induced obesity model. Selective targeting of ADAMTS5 could provide a new therapeutic strategy for treatment/prevention of NASH. PMID- 27254776 TI - 14-Vertex Heteroboranes with 14 Skeletal Electron Pairs: An Experimental and Computational Study. AB - Three isomers of [(Cp*Ru)2 C2 B10 H12 ], the first examples of 14-vertex heteroboranes containing 14-skeletal electron pairs, have been synthesized by the direct electrophilic insertion of a {Cp*Ru(+) } fragment into the anion [4-Cp* 4,1,6-RuC2 B10 H12 ](-) . All three compounds have the same unique polyhedral structure having an approximate Cs symmetry and featuring a four-atom trapezoidal face. X-ray diffraction studies could confidently identify only one of the two cage C atoms in each structure. The other C atom position has been established by a combination of i) best fitting of computed and experimental (11) B and (1) H NMR chemical shifts, and ii) consideration of the lowest computed energy for series of isomers studied by DFT calculations. In all three isomers, one cage C atom occupies a degree-4 vertex on the short parallel edge of the trapezium. PMID- 27254775 TI - Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell cell adhesion. AB - E-cadherin mediated cell-cell adhesion plays a critical role in epithelial cell polarization and morphogenesis. Our recent studies suggest that the desmosomal cadherin, desmoglein 3 (Dsg3) cross talks with E-cadherin and regulates its adhesive function in differentiating keratinocytes. However, the underlying mechanism remains not fully elucidated. Since E-cadherin trafficking has been recognized to be a central determinant in cell-cell adhesion and homeostasis we hypothesize that Dsg3 may play a role in regulating E-cadherin trafficking and hence the cell-cell adhesion. Here we investigated this hypothesis in cells with loss of Dsg3 function through RNAi mediated Dsg3 knockdown or the stable expression of the truncated mutant Dsg3DeltaC. Our results showed that loss of Dsg3 resulted in compromised cell-cell adhesion and reduction of adherens junction and desmosome protein expression as well as the cortical F-actin formation. As a consequence, cells failed to polarize but instead displayed aberrant cell flattening. Furthermore, retardation of E-cadherin internalization and recycling was consistently observed in these cells during the process of calcium induced junction assembling. In contrast, enhanced cadherin endocytosis was detected in cells with overexpression of Dsg3 compared to control cells. Importantly, this altered cadherin trafficking was found to be coincided with the reduced expression and activity of Rab proteins, including Rab5, Rab7 and Rab11 which are known to be involved in E-cadherin trafficking. Taken together, our findings suggest that Dsg3 functions as a key in cell-cell adhesion through at least a mechanism of regulating E-cadherin membrane trafficking. PMID- 27254777 TI - Autoimmune hepatitis and long-term disease course in children in Turkey, a single center experience. AB - INTRODUCTION: The aim of this study is to determine clinic and laboratory features, treatment protocols, treatment responses, and long term follow-up of children with autoimmune hepatitis (AIH) in a region of Turkey followed at Ege University. MATERIALS AND METHODS: The records of 47 children with AIH between 1998 and 2012 were retrospectively analyzed for clinical profiles, treatment response, relapse rate, and long-term side effects. RESULTS: The median age of the children was 10+/-4.1 years (55.3% females). A total of 29 patients presented with chronic hepatitis (61.7%). According to the autoantibody profiles, 40 (85.1%) and seven (14.9%) cases were classified as type 1 and type 2, respectively. Presentation with acute hepatitis and chronic hepatitis was significantly higher in type 1 disease. Laboratory findings at presentation was found similar among races as well as AIH types (P>0.05). The prednisolone was used for remission induction in 37 patients; 86.4% (n: 32) achieved a complete response, 2.7% (n: 1) achieved a partial response, and four patients (10.8%) showed no response. Maintenance was attained by low-dose steroid plus thiopurine and relapse in steroid responders (n: 32) was 9.4% (n: 3) at 8, 12, and 48 months. A total of 36% (n: 24) had neither acute nor chronic treatment side effects. Bone marrow suppression was observed in five patients and hyperglycemia was observed in one patient (10.6 and 2.1%), respectively. CONCLUSION: AIH type 1 prevails in children in a region of Turkey during the second decade of life. Low dose corticosteroids combined with azathioprine are found. PMID- 27254778 TI - Inverted intramucosal carcinoma in the sigmoid colon. PMID- 27254779 TI - Effects of extremely low-frequency magnetotherapy on proliferation of human dermal fibroblasts. AB - Extremely low-frequency electromagnetic fields (ELF-EMFs) applied in magnetotherapy have frequency lower than 100 Hz and magnetic field intensity ranging from 0.1 to 20 mT. For many years, the use of magnetotherapy in clinics has been increasing because of its beneficial effects in many processes, e.g., skin diseases, inflammation and bone disorders. However, the understanding of the microscopic mechanisms governing such processes is still lacking and the results of the studies on the effects of ELF-EMFs are controversial because effects derive from different conditions and from intrinsic responsiveness of different cell types.In the present study, we studied the biological effects of 1.5 h exposure of human dermal fibroblasts to EMFs with frequencies of 5 and 50 Hz and intensity between 0.25 and 1.6 mT. Our data showed that the magnetic treatment did not produce changes in cell viability, but gave evidence of a sizeable decrease in proliferation at 24 h after treatment. In addition, immunofluorescence experiments displayed an increase in tubulin expression that could foreshadow changes in cell motility or morphology. The decrease in proliferation with unchanged viability and increase in tubulin expression could be consistent with the triggering of a transdifferentiation process after the exposure to ELF-EMFs. PMID- 27254780 TI - QuickStats: Age-Adjusted Prevalence*(,)(?) of Hypertension Treatment(S) Among Adults Aged >=18 Years with Hypertension,( ) by Sex and Race/Ethnicity - National Health and Nutrition Examination Survey, United States, 2011-2014. AB - During 2011-2014, 74.6% of adults aged >=18 years with hypertension reported taking antihypertensive medication. Overall, a smaller percentage of non-Hispanic Asian adults (63.8%) with hypertension reported taking antihypertensive medication compared with non-Hispanic white (75.8%), non-Hispanic black (77.3%), and Hispanic (70.7%) adults with hypertension. This pattern was found for both men and women with one exception: the difference between non-Hispanic Asian men and Hispanic men was not significant. A larger percentage of non-Hispanic white, non-Hispanic black, and Hispanic women reported taking antihypertensive medication than did their male counterparts. PMID- 27254781 TI - Amino-Functionalized Layered Crystalline Zirconium Phosphonates: Synthesis, Crystal Structure, and Spectroscopic Characterization. AB - Two new layered zirconium phosphonates functionalized with amino groups were synthesized starting from aminomethylphosphonic acid in the presence of different mineralizers, and their structures were solved from powder X-ray diffraction data. Their topologies are unprecedented in zirconium phosphonate chemistry: the first, of formula ZrH[F3(O3PCH2NH2)], prepared in the presence of hydrofluoric acid, features uncommon ZrO2F4 units and a remarkable thermal stability; the second, of formula Zr2H2[(C2O4)3(O3PCH2NH2)2].2H2O, prepared in the presence of oxalic acid, is based on ZrO7 units with oxalate anions coordinated to the metal atom, which were never observed before in any zirconium phosphonate. In addition, the structure of another compound based on (2-aminoethyl)phosphonic acid is reported, which was the object of a previously published study. This compound has layered alpha-type structure with -NH3(+) groups located in the interlayer space. All of the reported compounds were further characterized by means of vibrational spectroscopy, which provided important information on fine structural details that cannot be deduced from the powder X-ray diffraction data. PMID- 27254782 TI - N-Benzylpiperidine Derivatives as alpha7 Nicotinic Receptor Antagonists. AB - A series of multitarget directed propargylamines, as well as other differently susbstituted piperidines have been screened as potential modulators of neuronal nicotinic acetylcholine receptors (nAChRs). Most of them showed antagonist actions on alpha7 nAChRs. Especially, compounds 13, 26, and 38 displayed submicromolar IC50 values on homomeric alpha7 nAChRs, whereas they were less effective on heteromeric alpha3beta4 and alpha4beta2 nAChRs (up to 20-fold higher IC50 values in the case of 13). Antagonism was concentration dependent and noncompetitive, suggesting that these compounds behave as negative allosteric modulators of nAChRs. Upon the study of a series of less complex derivatives, the N-benzylpiperidine motif, common to these compounds, was found to be the main pharmacophoric group. Thus, 2-(1-benzylpiperidin-4-yl)-ethylamine (48) showed an inhibitory potency comparable to the one of the previous compounds and also a clear preference for alpha7 nAChRs. In a neuroblastoma cell line, representative compounds 13 and 48 also inhibited, in a concentration-dependent manner, cytosolic Ca(2+) signals mediated by nAChRs. Finally, compounds 38 and 13 inhibited 5-HT3A serotonin receptors whereas they had no effect on alpha1 glycine receptors. Given the multifactorial nature of many pathologies in which nAChRs are involved, these piperidine antagonists could have a therapeutic potential in cases where cholinergic activity has to be negatively modulated. PMID- 27254783 TI - Transcriptomic and Physiological Responses of the Green Microalga Chlamydomonas reinhardtii during Short-Term Exposure to Subnanomolar Methylmercury Concentrations. AB - The effects of short-term exposure to subnanomolar methyl-mercury (MeHg) concentrations, representative of contaminated environments, on the microalga Chlamydomonas reinhardtii were assessed using both physiological end points and gene expression analysis. MeHg bioaccumulated and induced significant increase of the photosynthesis efficiency, while the algal growth, oxidative stress, and chlorophyll fluorescence were unaffected. At the molecular level, MeHg significantly dysregulated the expression of genes involved in motility, energy metabolism, lipid metabolism, metal transport, and antioxidant enzymes. Data suggest that the cells were able to cope with subnanomolar MeHg exposure, but this tolerance resulted in a significant cost to the cell energy and reserve metabolism as well as ample changes in the nutrition and motility of C. reinhardtii. The present results allowed gaining new insights on the effects and uptake mechanisms of MeHg at subnanomolar concentrations in aquatic primary producers. PMID- 27254784 TI - Endothelial Monocyte-Activating Polypeptide II Mediates Macrophage Migration in the Development of Hyperoxia-Induced Lung Disease of Prematurity. AB - Myeloid cells are key factors in the progression of bronchopulmonary dysplasia (BPD) pathogenesis. Endothelial monocyte-activating polypeptide II (EMAP II) mediates myeloid cell trafficking. The origin and physiological mechanism by which EMAP II affects pathogenesis in BPD is unknown. The objective was to determine the functional consequences of elevated EMAP II levels in the pathogenesis of murine BPD and to investigate EMAP II neutralization as a therapeutic strategy. Three neonatal mouse models were used: (1) BPD (hyperoxia), (2) EMAP II delivery, and (3) BPD with neutralizing EMAP II antibody treatments. Chemokinic function of EMAP II and its neutralization were assessed by migration in vitro and in vivo. We determined the location of EMAP II by immunohistochemistry, pulmonary proinflammatory and chemotactic gene expression by quantitative polymerase chain reaction and immunoblotting, lung outcome by pulmonary function testing and histological analysis, and right ventricular hypertrophy by Fulton's Index. In BPD, EMAP II initially is a bronchial club-cell specific protein-derived factor that later is expressed in galectin-3+ macrophages as BPD progresses. Continuous elevated expression corroborates with baboon and human BPD. Prolonged elevation of EMAP II levels recruits galectin-3+ macrophages, which is followed by an inflammatory state that resembles a severe BPD phenotype characterized by decreased pulmonary compliance, arrested alveolar development, and signs of pulmonary hypertension. In vivo pharmacological EMAP II inhibition suppressed proinflammatory genes Tnfa, Il6, and Il1b and chemotactic genes Ccl2 and Ccl9 and reversed the severe BPD phenotype. EMAP II is sufficient to induce macrophage recruitment, worsens BPD progression, and represents a targetable mechanism of BPD development. PMID- 27254785 TI - Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling. AB - We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs bridged interaction between the Lewis-basic C-terminal carboxylate of the peptides with the distal arene of the substrate. PMID- 27254786 TI - Novel porous gold-palladium nanoalloy network-supported graphene as an advanced catalyst for non-enzymatic hydrogen peroxide sensing. AB - In an effort to develop electrocatalysts associated with effective design, testing, and fabrication, novel porous gold-palladium nanoalloy network-supported graphene (AuPd@GR) nanohybrids were successfully synthesized via electroless deposition followed by a chemical vapor deposition (CVD) method for the first time. The AuPd@GR nanohybrids were obtained as a continuous, porous, transparent, bendable, and ultrathin film with good assembly of the AuPd nanoalloy particles (<10nm) within the GR. The AuPd@GR nanohybrids exhibited excellent catalytic activity towards H2O2 detection with a wide detection range (5MUM-11.5mM), high sensitivity (186.86MUAmM(-1)cm(-2)), low limit of detection (1MUM), fast response (3s), and long-term working stability (2500s). Furthermore, the AuPd@GR nanohybrids demonstrated outstanding durability, along with negligible interference from ascorbic acid, dopamine, uric acid, urea, potassium ions, chloride ions, and glucose. These findings open a new pathway to fabricate electrocatalysts for application in high performance electrochemical sensors and bioelectronics. PMID- 27254787 TI - Nonenzymatic all-solid-state coated wire electrode for acetylcholine determination in vitro. AB - A nonenzymatic all-solid-state coated wire acetylcholine electrode was investigated. Poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate) (PEDOT/PSS) as conducting polymer was coated on one end of a gold wire (0.5mm in diameter). The acetylcholine selective membrane containing heptakis(2,3,6-tri Omicron-methyl)-beta-cyclodextrin as an ionophore covered the conducting polymer layer. The electrode could work stably in a pH range of 6.5-8.5 and a temperature range of 15-40 degrees C. It covered an acetylcholine concentration range of 10( 5)-10(-1)M with a slope of 54.04+/-1.70mV/decade, while detection limit was 5.69+/-1.06uM. The selectivity, dynamic response, reproducibility and stability were evaluated. The electrode could work properly in the rat brain homogenate to detect different concentrations of acetylcholine. PMID- 27254788 TI - Time Course of Tactile Gating in a Reach-to-Grasp and Lift Task. AB - Humans' sensory systems are bombarded by myriad events every moment of our lives. Thus, it is crucial for sensory systems to choose and process critical sensory events deemed important for a given task and, indeed, those that affect survival. Tactile gating is well known, and defined as a reduced ability to detect and discriminate tactile events before and during movement. Also, different locations of the effector exhibit different magnitudes of sensitivity changes. The authors examined that time course of tactile gating in a reaching and grasping movement to characterize its behavior. Tactile stimulators were attached to the right and left mid-forearms and the right index finger and fifth digit. When participants performed reach-to-grasp and lift targets, tactile acuity decreased at the right forearm before movement onset (F. L. Colino, G. Buckingham, D. T. Cheng, P. van Donkelaar, & G. Binsted, 2014 ). However, tactile sensitivity at the right index finger decreased by nearly 20% contrary to expectations. This result reflecting that there may be an additional source acting to reduce inhibition related to tactile gating. Additionally, sensitivity improved as movement end approached. Collectively, the present results indicate that predictive and postdictive mechanisms strongly influence tactile gating. PMID- 27254789 TI - New Understanding of Age-Related Macular Degeneration Through Quantitative Autofluorescence. PMID- 27254790 TI - An antiarrhythmic agent as a promising lead compound for targeting the hEAG1 ion channel in cancer therapy: insights from molecular dynamics simulations. AB - Experimental evidence suggests that hERG and hEAG potassium channels may serve as important cancer therapy targets because either of the channel blockade or inactivation by different methods leads to inhibition of cancer cells growth and proliferation. However, there is no known hEAG specific blocker, and hERG blockade leads to adverse cardiac side effects, although it is currently used in treating certain types of arrhythmias. There have been some attempts to explain the channels blockade by clofilium, an antiarrhythmic agent, and the results lead to different possible binding modes. This study investigates for the first time the potential of using clofilium as a lead compound for finding a novel cancer therapy agent which may target ion channels. The implied findings from a comparative assessment of literature studies were verified using molecular dynamics simulations. The results indicate a particular structural difference between the two channels that could provide a novel and realistic way of using clofilium analogs which may target the hEAG1 ion channel in cancer therapy. PMID- 27254791 TI - Training for the future. PMID- 27254792 TI - Emergence of family medicine in Ethiopia [corrected]: an international collaborative education model. AB - Family Medicine (FM) is a new specialty in Ethiopia. The first seven family physicians graduated in February 2016 from the inaugural residency programme at Addis Ababa University. Cooperation amongst Ethiopian and expatriate decision makers and physicians was needed to begin the programme. Intentional replacement of expatriates with Ethiopian family physicians has begun. Barriers include lack of understanding of FM and the human and financial resources needed for scaling up the programme. Regular programme review with resident physician involvement has allowed the FM training programme to adapt and fit the Ethiopian context. Further successes will result from ongoing support and advocacy from the Federal Ministry of Health and other Ethiopian, African, and international primary care organisations. PMID- 27254795 TI - Unsaturated amino acids derived from isoleucine trigger early membrane effects on plant cells. AB - Unsaturated amino acids (UnsAA) have been shown to affect the activity of various biological processes. However, their mode of action has been investigated poorly thus far. We show in this work that 2-amino-3-methyl-4-pentenoic acid (C2) and 2 amino-3-methyl-4-pentynoic acid (C3) structurally derived from isoleucine (Ile) exhibited a multisite action on plant cells. For one, C2 and C3 induced early modifications at the plasma membrane level, as shown by the hyperpolarization monitored by microelectrode implantation in the pulvinar cells of Mimosa pudica, indicating that these compounds are able to modify ionic fluxes. In particular, proton (H(+)) fluxes were modified, as shown by the pH rise monitored in the bathing medium of pulvinar tissues. A component of this effect may be linked to the inhibitory effect observed on the proton pumping and the vanadate-sensitive activity of the plasma membrane H(+)-ATPase monitored in plasma membrane vesicles (PMVs) purified from pulvinar tissues of M. pudica and leaf tissues of Beta vulgaris. This effect may explain, in part, the inhibitory effect of the compounds on the uptake capacity of sucrose and valine by B. vulgaris leaf tissues. In contrast, an unexpected action was observed in cell reactions, implicating ion fluxes and water movement. Indeed, the osmocontractile reactions of pulvini induced either by a mechanical shock in M. pudica or by dark and light signals in Cassia fasciculata were increased, indicating that, compared to Ile, these compounds may modify in a specific way the plasma membrane permeability to water and ions. PMID- 27254797 TI - Probing Rubber Cross-Linking Generation of Industrial Polymer Networks at Nanometer Scale. AB - We present improved analyses of rheometric torque measurements as well as (1)H double-quantum (DQ) nuclear magnetic resonance (NMR) buildup data on polymer networks of industrial compounds. This latter DQ NMR analysis allows finding the distribution of an orientation order parameter (Dres) resulting from the noncomplete averaging of proton dipole-dipole couplings within the cross-linked polymer chains. We investigate the influence of the formulation (filler and vulcanization systems) as well as the process (curing temperature) ending to the final polymer network. We show that DQ NMR follows the generation of the polymer network during the vulcanization process from a heterogeneous network to a very homogeneous one. The time variations of microscopic Dres and macroscopic rheometric torques present power-law behaviors above a threshold time scale with characteristic exponents of the percolation theory. We observe also a very good linear correlation between the kinetics of Dres and rheometric data routinely performed in industry. All these observations confirm the description of the polymer network generation as a critical phenomenon. On the basis of all these results, we believe that DQ NMR could become a valuable tool for investigating in situ the cross-linking of industrial polymer networks at the nanometer scale. PMID- 27254796 TI - Genome-wide identification of blood DNA methylation patterns associated with early-onset hepatocellular carcinoma development in hepatitis B carriers. AB - The etiology of early-onset hepatocellular carcinoma (HCC) among hepatitis B virus (HBV) carriers remains unclear. DNA methylation levels in peripheral leukocytes have been associated with different environmental exposures and immune or inflammatory response. We aimed to identify methylation signatures of peripheral leukocytes that could track hepatitis B progression to HCC, especially for early-onset HCC. We first performed an epigenome-wide association analysis on 48 matched case-control pairs in a nested case-control study within a 22-yr follow-up cohort of HBV carriers. Through this analysis we found that progression to early-onset HCC involved methylation variable positions across the genome, in which a substantial proportion displayed significant variation due to HBV viral load, chronic hepatitis status, and/or leukocyte subtype composition, and these associations were significantly enriched among genes in immune pathways. Methylation at probes cg00300879, cg06872964, and cg07080864, that are located within the proximal promoter of CNKSR1, IFI44L, and PENK, respectively, was validated by bisulfite pyrosequencing and findings were replicated in a case sibling study of early-onset HCC (134 cases vs. 174 sibling controls). Furthermore, a high methylation score, constructed using the three probes, was predictive for the risk of early-onset HCC in two datasets (adjusted-odds ratios = 0.21-0.32, P <= 0.0206). This association was also observed for late-onset HCC (adjusted-odds ratio = 0.42-0.47, P <= 0.0194) in a nested case-control study (120 cases vs. 178 controls). In prospective analysis, change in the score was detected 5-9 yr before HCC onset. Blood-based methylation profiling provides new insights into the complexity of virus-host interaction underlying HBV-related HCC, holding promise for the disease risk management. (c) 2016 Wiley Periodicals, Inc. PMID- 27254798 TI - Small Molecule Restores Itaconate Sensitivity in Salmonella enterica: A Potential New Approach to Treating Bacterial Infections. AB - In the context of increasing global antibiotic resistance, the need for alternative therapeutic targets is great. Although new antibiotics and resistance inhibitors provide temporary solutions, they are bound to become obsolete. In this work, we propose a new approach, coined "bacterio-modulation" that aims to restore macrophage potency towards bacterial strains that are able to survive in phagolysosomes. One key defense in the macrophage's arsenal is itaconate, an endogenous molecule with antimicrobial activity. Some intracellular pathogens have evolved to produce itaconate-degrading enzymes, which are required for intracellular proliferation and to promote pathogenicity. We herein present the first molecule able to resensitize Salmonella enterica to itaconate. PMID- 27254799 TI - Concussion and Psychiatric Outcome in Adults and Children. PMID- 27254800 TI - A Systematic Review of Psychiatric, Psychological, and Behavioural Outcomes following Mild Traumatic Brain Injury in Children and Adolescents. AB - BACKGROUND: Evidence regarding longer-term psychiatric, psychological, and behavioural outcomes (for example, anxiety, mood disorders, depression, and attention disorders) following mild traumatic brain injury (mTBI) in children and adolescents has not been previously synthesized. OBJECTIVE: To conduct a systematic review of the available evidence examining psychiatric, psychological, and behavioural outcomes following mTBI in children and adolescents. MATERIALS AND METHODS: Nine electronic databases were systematically searched from 1980 to August 2014. Studies selected met the following criteria: original data; study design was a randomized controlled trial, quasi-experimental design, cohort or historical cohort study, case-control study, or cross-sectional study; exposure included mTBI (including concussion); population included children and adolescents (<19 years) at the time of mTBI, as well as a comparison group (for example, healthy children, children with orthopaedic injuries); and included psychiatric, psychological, or behavioural outcomes (for example, anxiety, mood disorders, depression, attention disorders). Two authors independently assessed the quality and level of evidence with the Downs and Black (DB) criteria and Oxford Centre of Evidence-Based Medicine (OCEBM) model, respectively, for each manuscript. RESULTS: Of 9472 studies identified in the initial search, 30 were included and scored. Heterogeneity in methodology and injury definition precluded meta-analyses. The median methodological quality for all 30 studies, based on the DB criteria, was 15/33 (range 6 to 19). The highest level of evidence demonstrated by all reviewed studies was level 2b based on OCEBM criteria, with the majority (28/30 studies) classified at this level. Based on the literature included in this systematic review, psychological and psychiatric problems in children with a history of mTBI were found to be more prevalent when mTBI is associated with hospitalization, when assessment occurs earlier in the recovery period (that is, resolves over time), when there are multiple previous mTBIs, in individuals with preexisting psychiatric illness, when outcomes are based on retrospective recall, and when the comparison group is noninjured healthy children (as opposed to children with injuries not involving the head). CONCLUSIONS: Overall, few rigorous prospective studies have examined psychological, behavioural, and psychiatric outcomes following mTBI. In the absence of true reports of preinjury problems and when ideally comparing mild TBI to non-TBI injured controls, there is little evidence to suggest that psychological, behavioural, and/or psychiatric problems persist beyond the acute and subacute period following an mTBI in children and adolescents. PMID- 27254801 TI - Knowing What We Don't Know: Long-Term Psychiatric Outcomes following Adult Concussion in Sports. AB - OBJECTIVE: Amidst a growing concern regarding concussion in sports, there is an emerging link between sport concussion and mental health outcomes. This review summarizes the current literature addressing long-term psychiatric sequelae associated with sport concussion in adults. METHOD: Several databases were searched using a broad list of keywords for each of concussion, sports, and mental health, with a resultant 311 studies for initial review. After limiting studies based on duplication, appropriateness of data, and relevance, 21 studies remained pertaining to depression, anxiety, substance use, and behavioural changes, including those highlighting chronic traumatic encephalopathy (CTE). RESULTS: Most studies identified suggested an increased prevalence of depressive symptoms related to concussion history. A conference abstract and qualitative study suggested increasing anxiety related to concussion history; however, a PhD dissertation found no relationship. In reviewing substance use, several studies mentioned use in athletes suspected of having concussion histories, although no link was established, while another noted undiagnosed concussion as leading to current substance misuse. Regarding behavioural changes, all studies identified occurrences of behaviour and/or cognitive changes in participants, with 2 studies suggesting a link with concussion history. With respect to CTE, concerns with mood, behaviour, cognition, and substance use were consistently highlighted, suggesting relations to previous sport concussion; however, the notion of different CTE subtypes and clear aetiology behind concussion severity or frequency was not consistently elucidated. CONCLUSION: There appears to be a growing body of evidence supporting the presence of long-term psychiatric and psychological sequelae following sport concussion in adults. PMID- 27254802 TI - No Mental Health without Oral Health. AB - The poor physical health faced by people with mental illness has been the subject of growing attention, but there has been less focus on the issue of oral health even though it is an important part of physical health. This article discusses the two-way association between oral and mental health. In one direction, the prospect of dental treatment can lead to anxiety and phobia. In the other, many psychiatric disorders, such as severe mental illness, affective disorders, and eating disorders, are associated with dental disease: These include erosion, caries, and periodontitis. Left untreated, dental diseases can lead to teeth loss such that people with severe mental illness have 2.7 times the likelihood of losing all their teeth, compared with the general population. Possible interventions include oral health assessments using standard checklists that can be completed by nondental personnel, help with oral hygiene, management of iatrogenic dry mouth, and early dental referral. PMID- 27254803 TI - Apgar Scores Are Associated with Attention-Deficit/Hyperactivity Disorder Symptom Severity. AB - OBJECTIVE: Adverse events during pregnancy and delivery have been linked to attention-deficit/hyperactivity disorder (ADHD). Previous studies have investigated Apgar scores, which assess the physical condition of newborns, in relation to the risk of developing ADHD. We propose to go one step further and examine if Apgar scores are associated with ADHD symptom severity in children already diagnosed with ADHD. METHOD: ADHD symptoms severity, while off medication, was compared in 2 groups of children with ADHD: those with low (<=6, n = 52) and those with higher (>=7, n = 400) Apgar scores sequentially recruited from the ADHD clinic. RESULTS: Children with low Apgar at 1 minute after birth had more severe symptoms as assessed by the externalizing scale of the Child Behaviour Checklist, the Conners' Global Index for Parents, and the DSM-IV hyperactivity symptoms count (P = 0.02, <0.01, <0.01, respectively). CONCLUSION: Low 1-minute Apgar scores are associated with a significant increase in ADHD symptom severity. These findings underline the importance of appropriate pregnancy and perinatal care. PMID- 27254804 TI - Dopamine 2 Receptor Genes Are Associated with Raised Blood Glucose in Schizophrenia. AB - OBJECTIVE: Type 2 diabetes is commonly found in schizophrenia and is an important contributor to mortality and morbidity in this condition. Dopamine has been implicated in the aetiology of both diabetes and schizophrenia. It is possible that both disorders share a common genetic susceptibility. METHODS: In a cross sectional study, we examined 2 dopamine D2 receptor (DRD2) single-nucleotide polymorphisms (SNPs) previously associated with schizophrenia (C939 T, rs6275 and C957 T, rs6277) along with fasting blood glucose and body mass index (BMI) in 207 antipsychotic-treated patients with schizophrenia. All participants met DSM-IV criteria for schizophrenia, and those with other psychiatric disorders were excluded. Analysis of covariance was used to compare fasting glucose results by DRD2 genotypes, after controlling for known confounds. For significant associations, follow-up Bonferroni post hoc tests examined differences in fasting glucose levels between genotypes. Specific comparisons were also made using analysis of variance and chi-square (Fisher's exact test). RESULTS: The 2 DRD2 risk genotypes were associated with significant increases in blood glucose, after controlling for BMI, age, sex, dosage and type of antipsychotic medication, number of hospitalisations, and negative symptoms (rs6275, F(2, 182) = 5.901, P = 0.003; rs6277 SNP, F(2, 178) = 3.483, P = 0.033). CONCLUSIONS: These findings support the involvement of DRD2 not only in schizophrenia but also in elevated levels of blood glucose commonly found in antipsychotic-treated patients with schizophrenia. Our data support the notion that diabetes may not merely be a comorbid condition but could be fundamentally associated with the pathogenesis of schizophrenia itself. PMID- 27254806 TI - Potential for Drug-Drug Interactions with Adjunctive Tramadol Use in Treatment of Obsessive-Compulsive Disorder. PMID- 27254805 TI - Racial Discrimination, Cultural Resilience, and Stress. AB - OBJECTIVE: Racial discrimination is a social determinant of health for First Nations people. Cultural resilience has been regarded as a potentially positive resource for social outcomes. Using a compensatory model of resilience, this study sought to determine if cultural resilience (compensatory factor) neutralized or offset the detrimental effect of racial discrimination (social risk factor) on stress (outcome). METHODS: Data were collected from October 2012 to February 2013 (N = 340) from adult members of the Kettle and Stony Point First Nation community in Ontario, Canada. The outcome was perceived stress; risk factor, racial discrimination; and compensatory factor, cultural resilience. Control variables included individual (education, sociability) and family (marital status, socioeconomic status) resilience resources and demographics (age and gender). The model was tested using sequential regression. RESULTS: The risk factor, racial discrimination, increased stress across steps of the sequential model, while cultural resilience had an opposite modest effect on stress levels. In the final model with all variables, age and gender were significant, with the former having a negative effect on stress and women reporting higher levels of stress than males. Education, marital status, and socioeconomic status (household income) were not significant in the model. The model had R(2) = 0.21 and adjusted R(2) = 0.18 and semipartial correlation (squared) of 0.04 and 0.01 for racial discrimination and cultural resilience, respectively. CONCLUSIONS: In this study, cultural resilience compensated for the detrimental effect of racial discrimination on stress in a modest manner. These findings may support the development of programs and services fostering First Nations culture, pending further study. PMID- 27254807 TI - Dual-Polymer Drops, Contact Lens Comfort, and Lid Wiper Epitheliopathy. AB - PURPOSE: This study compared a new contact lens rewetting drop containing both carboxymethylcellulose and hyaluronic acid (CMC-HA) with a standard drop containing carboxymethylcellulose only (CMC). Symptoms of discomfort typical in lens wear and lid wiper epitheliopathy (LWE) were assessed over a 3-month period in a diverse sample of contact lens wearers. METHODS: Adapted daily-wear contact lens subjects using hydrogel, silicone hydrogel, or rigid gas permeable lenses were enrolled in this prospective, randomized, double-masked, parallel-group, 90 day study conducted at 15 clinical sites. Subjects were randomized 2:1 to CMC-HA (n = 244) or CMC alone (n = 121) with dosage at least four times per day, along with their habitual lens care system. At baseline and at days 7, 30, 60, and 90, subject-completed questionnaires, bulbar conjunctival staining, LWE, contact lens distance visual acuity (CLDVA), and standard safety measures were assessed. RESULTS: At day 90, CMC-HA performed significantly better than CMC in ocular symptoms including dryness throughout the day (p = 0.006), and burning/stinging throughout the day (p = 0.02) and at the end of the day (p < 0.001). CMC-HA also performed numerically better for dryness at the end of day (p = 0.06). LWE staining was improved in the CMC-HA group at day 90 whereas it increased slightly in the CMC alone group, with a significant between-group difference (p = 0.009). CMC-HA also demonstrated greater reduction in conjunctival staining compared with CMC alone at day 90 (p = 0.08). No differences in CLDVA, contact lens wear time, acceptability, and product use were observed, and safety outcomes were similar between groups. CONCLUSIONS: The addition of HA to a standard CMC rewetting drop improves clinical performance. In this comparison of rewetting drop efficacy in contact lens wearers, LWE was a useful clinical sign for differentiating clinical performance. PMID- 27254808 TI - Demographic Factors Affect Ocular Comfort Ratings During Contact Lens Wear. AB - PURPOSE: To determine if rating of ocular comfort during soft contact lens wear is affected by demographic factors. METHODS: Retrospective analysis of ocular comfort ratings during soft contact lens wear extracted from 44 nonrandomized similar clinical trials (n = 986). Subjects wore one of seven daily wear silicone hydrogels (SiHy) in combination with one of nine lens care products (LCP), and two daily disposables lenses. The effects on comfort rating of demographic factors were examined after adjusting for lens and LCP effects using general linear model. RESULTS: Males reported lower comfort on insertion than females (7.9 +/- 1.6 vs. 8.1 +/- 1.6, p = 0.001). Over 45 years old had higher comfort ratings than those between 26 and 45 or <26 years old at insertion (8.7 +/- 1.3 vs. 8.1 +/- 1.6 vs. 7.8 +/- 1.6, p < 0.001), during the day (8.6 +/- 1.2 vs. 8.0 +/- 1.6 vs. 8.2 +/- 1.2, p < 0.001), and end of day (7.7 +/- 1.6 vs. 6.8 +/- 2.0 vs. 7.0 +/- 1.6, p < 0.001). Neophytes reported lower comfort on insertion (7.3 +/- 1.6 vs. 8.2 +/- 1.5, p < 0.001) and during day (8.0 +/- 1.3 vs. 8.3 +/- 1.3, p = 0.020) than experienced wearers. Participants with Rx >=-3.50D had higher comfort ratings than those with <=-3.50D on insertion (8.3 +/- 1.4 vs. 7.8 +/- 1.6, p < 0.001), during the day (8.4 +/- 1.3 vs. 8.1 +/- 1.3, p = 0.010), and end of day (7.2 +/- 1.7 vs. 6.9 +/- 1.8, p = 0.046). Comfort during the day was different between participants of different ethnic origin (p = 0.024) with Asians reporting the lowest (8.1 +/- 1.3). CONCLUSIONS: Demographic factors such as age, gender, lens wear experience, ethnicity, and refractive status can influence the rating of ocular comfort in clinical studies. The confounding effects of such demographic factors can be controlled by implementing randomization and appropriate multivariable statistical analysis. PMID- 27254809 TI - Microbial Contamination of Contact Lens Storage Cases During Daily Wear Use. AB - PURPOSE: To evaluate contact lens (CL) storage case contamination when used with four different CL care solutions during daily wear of three different CL materials. METHODS: A parallel, prospective, bilateral, randomized clinical trial (n = 38) was conducted. Subjects were randomly assigned to use one of three CL materials (etafilcon A, senofilcon A, or galyfilcon A) on a daily wear basis. Subsequently, each subject randomly used one of four different CL care solutions (Biotrue, OPTI-FREE PureMoist, RevitaLens OcuTec, and CLEAR CARE) for 2 weeks, along with their respective storage cases. After every 2-week period, their storage cases were collected and the right and left wells of each storage case were randomized for two procedures: (1) microbial enumeration by swabbing the storage case surface and (2) evaluation of biofilm formation (multipurpose solution cases only) using a crystal violet staining assay. RESULTS: More than 80% of storage cases were contaminated when used in conjunction with the four CL care solutions, irrespective of the CL material worn. Storage cases maintained with CLEAR CARE (mean Log colony forming units (CFU)/well +/- SD, 2.0 +/- 1.0) revealed significantly (p < 0.001) greater levels of contamination, compared to those maintained with Biotrue (1.3 +/- 0.8) and RevitaLens OcuTec (1.2 +/- 0.8). Predominantly, storage cases were contaminated with Gram-positive bacteria (>=80%). There were significant differences (p = 0.013) for the levels of Gram negative bacteria recovered from the storage cases maintained with different CL care solutions. Storage cases maintained with OPTI-FREE PureMoist (0.526 +/- 0.629) showed significantly higher biofilm formation (p = 0.028) compared to those maintained with Biotrue (0.263 +/- 0.197). CONCLUSIONS: Levels of contamination ranged from 0 to 6.4 Log CFU/storage case well, which varied significantly (p < 0.001) between different CL care solutions, and storage case contamination was not modulated by CL materials. PMID- 27254810 TI - Developing a Very Low Vision Orientation and Mobility Test Battery (O&M-VLV). AB - PURPOSE: This study aimed to determine the feasibility of an assessment of vision related orientation and mobility (O&M) tasks in persons with severe vision loss. These tasks may be used for future low vision rehabilitation clinical assessments or as outcome measures in vision restoration trials. METHODS: Forty legally blind persons (mean visual acuity logMAR 2.3, or hand movements) with advanced retinitis pigmentosa participated in the Orientation & Mobility-Very Low Vision (O&M-VLV) subtests from the Low Vision Assessment of Daily Activities (LoVADA) protocol. Four categories of tasks were evaluated: route travel in three indoor hospital environments, a room orientation task (the "cafe"), a visual exploration task (the "gallery"), and a modified version of the Timed Up and Go (TUG) test, which assesses re-orientation and route travel. Spatial cognition was assessed using the Stuart Tactile Maps test. Visual acuity and visual fields were measured. RESULTS: A generalized linear regression model showed that a number of measures in the O&M-VLV tasks were related to residual visual function. The percentage of preferred walking speed without an aid on three travel routes was associated with visual field (p < 0.01 for all routes) whereas the number of contacts with obstacles during route travel was associated with acuity (p = 0.001). TUG-LV task time was associated with acuity (p = 0.003), as was the cafe time and distance traveled (p = 0.006 and p < 0.001, respectively). The gallery score was the only measure that was significantly associated with both residual acuity and fields (p < 0.001 and p = 0.001, respectively). CONCLUSIONS: The O&M VLV was designed to capture key elements of O&M performance in persons with severe vision loss, which is a population not often studied previously. Performance on these tasks was associated with both binocular visual acuity and visual field. This new protocol includes assessments of orientation, which may be of benefit in vision restoration clinical trials. PMID- 27254811 TI - Treatment Zone Decentration During Orthokeratology on Eyes with Corneal Toricity. AB - PURPOSE: To compare the magnitude of treatment zone decentration between eyes with minimally toric corneas (<=1.50 DC, LoTor group) and eyes with moderately toric corneas (1.50 to 3.50 DC, HiTor group) after a single overnight wear of spherical orthokeratology lenses. METHODS: In the LoTor group, 21 participants (9 M, 12 F, 20-40 years) were fitted using a conventional fitting approach based on the flat corneal meridian. In the HiTor group, 12 participants (5 M, 7 F, 19-45 years) were fitted using the conventional fitting method in one eye (HiTor group I) and the other eye was fitted with a lens with slightly deeper sagittal height (HiTor group II). In all groups, BE spherical orthokeratology trial contact lenses (Boston XO) were used and corneal topography data (Medmont E300) were obtained at baseline and after a single overnight wear. The magnitude of treatment zone decentration relative to vertex normal was determined from corneal topography refractive power difference maps. Treatment zone parameters including magnitude and direction of decentration were analyzed and related to baseline corneal parameters. RESULTS: After a single overnight wear, the mean magnitude of treatment zone decentration was 0.48 +/- 0.20 mm in the LoTor group, 1.06 +/- 0.57 mm in HiTor group I, and 0.95 +/- 0.44 mm in HiTor group II. Treatment zone decentration in the LoTor group was significantly different from HiTor group I (p < 0.001), both fitted using a conventional fitting method. Treatment zone decentration was not significantly different between HiTor group I and II (p = 0.606). The magnitude of treatment zone decentration was positively correlated with the amount of baseline corneal toricity (LoTor and HiTor group I combined, p = 0.048). CONCLUSIONS: Eyes with higher amounts of corneal toricity give rise to increased amounts of treatment zone decentration in overnight orthokeratology. PMID- 27254812 TI - The role of three-dimensional power Doppler ultrasound parameters measured on hCG day in the prediction of pregnancy during in vitro fertilization treatment. AB - OBJECTIVE: To investigate the value of ultrasound for the assessment of endometrial receptivity during in vitro fertilization (IVF) and embryo transfer (ET). MATERIALS AND METHODS: Only those patients in their first IVF cycle, followed a standard long gonadotropin releasing hormone (GnRH) agonist long ovarian stimulation regimen, and had 2 highest scoring embryos transferred on day 3 were included in the study. A 3D ultrasound examination was performed on the day of human chorionic gonadotropin (hCG) injection to determine endometrial thickness, endometrial pattern, peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI) and resistance index (RI) of endometrial spiral arteries, endometrial volume, vascularization index (VI), flow index (FI) and vasculariztion flow index (VFI) of endometrial and subendometrial region. Analyses were carried on between pregnant and non-pregnant groups, and miscarriage and ongoing pregnant groups. RESULTS: 435 patients were included in the study, in which 235 (58.8%) got clinical pregnancy, and 49 suffered miscarriage. Patients in both pregnant group and non-pregnant group, and miscarriage and ongoing pregnant group did not show significant difference in endometrial thickness, endometrial volume, endometrial pattern, uterine PI, RI, S/D, endometrial and subendometrial VI, FI and VFI. In relative thin endometrium group, pregnant patients had similar endometrial thickness, endometrial volume, endometrial pattern, uterine PI, RI, S/D, endometrial and subendometrial VI, FI and VFI with non-pregnant patients. CONCLUSION: 3D PDUS parameters of endometrium measured on hCG day were not good predictors of pregnancy in IVF treatment, neither good predictors of ongoing pregnancy. PMID- 27254813 TI - Modelling climate change impacts on viticultural yield, phenology and stress conditions in Europe. AB - Viticulture is a key socio-economic sector in Europe. Owing to the strong sensitivity of grapevines to atmospheric factors, climate change may represent an important challenge for this sector. This study analyses viticultural suitability, yield, phenology, and water and nitrogen stress indices in Europe, for present climates (1980-2005) and future (2041-2070) climate change scenarios (RCP4.5 and 8.5). The STICS crop model is coupled with climate, soil and terrain databases, also taking into account CO2 physiological effects, and simulations are validated against observational data sets. A clear agreement between simulated and observed phenology, leaf area index, yield and water and nitrogen stress indices, including the spatial differences throughout Europe, is shown. The projected changes highlight an extension of the climatic suitability for grapevines up to 55 degrees N, which may represent the emergence of new winemaking regions. Despite strong regional heterogeneity, mean phenological timings (budburst, flowering, veraison and harvest) are projected to undergo significant advancements (e.g. budburst/harvest can be >1 month earlier), with implications also in the corresponding phenophase intervals. Enhanced dryness throughout Europe is also projected, with severe water stress over several regions in southern regions (e.g. southern Iberia and Italy), locally reducing yield and leaf area. Increased atmospheric CO2 partially offsets dryness effects, promoting yield and leaf area index increases in central/northern Europe. Future biomass changes may lead to modifications in nitrogen demands, with higher stress in northern/central Europe and weaker stress in southern Europe. These findings are critical decision support systems for stakeholders from the European winemaking sector. PMID- 27254814 TI - Vibrational Sum Frequency Generation Spectroscopy Study of Hydrous Species in Soda Lime Silica Float Glass. AB - It is generally accepted that the mechanical properties of soda lime silica (SLS) glass can be affected by the interaction between sodium ions and hydrous species (silanol groups and water molecules) in its surface region. While the amount of these hydrous species can be estimated from hydrogen profiles and infrared spectroscopy, their chemical environment in the glass network is still not well understood. This work employed vibrational sum frequency generation (SFG) spectroscopy to investigate the chemical environment of hydrous species in the surface region of SLS float glass. SLS float glass shows sharp peaks in the OH stretching vibration region in SFG spectra, while the OH stretch peaks of glasses that do not have leachable sodium ions and the OH peaks of water molecules in condensed phases are normally broad due to fast hydrogen bonding dynamics. The hydrous species responsible for the sharp SFG peaks for the SLS float glass were found to be thermodynamically more stable than physisorbed water molecules, did not exchange with D2O, and were associated with the sodium concentration gradient in the dealkalized subsurface region. These results suggested that the hydrous species reside in static solvation shells defined by the silicate network with relatively slow hydrogen bonding dynamics, compared to physisorbed water layers on top of the glass surface. A putative radial distribution of the hydrous species within the SLS glass network was estimated based on the OH SFG spectral features, which could be compared with theoretical distributions calculated from computational simulations. PMID- 27254815 TI - Hydrosilane-B(C6F5)3 adducts as activators in zirconocene catalyzed ethylene polymerization. AB - Hydrosilane-B(C6F5)3 adducts were found to activate zirconocene dihalides and generate ternary catalytic systems possessing moderate to high activity in ethylene polymerization to high density polyethylene (HDPE). The activation efficacy of the adducts increased with increasing hydride donor ability and decreased with steric crowding of the particular hydrosilane used. NMR investigation of the HSiEt3/B(C6F5)3/Cp*2ZrF2 system (Cp* = eta(5)-C5Me5) revealed the formation of a stable intermediate [Cp*2ZrF(FSiEt3 kappaF)](+)[HB(C6F5)3](-), whereas a crucial role of the [HB(C6F5)3](-) anion as a hydride donor for generation of an active cationic zirconium hydride center was elucidated. PMID- 27254816 TI - The role of vitamin K in vascular calcification of patients with chronic kidney disease. AB - Patients with chronic kidney disease (CKD) are prone to vascular calcification. Pathogenetic mechanisms of vascular calcifications have been broadly studied and discussed such as the role of hyperphosphatemia, hypercalcemia, parathormone, and vitamin D. In recent years, new insights have been gained pointing to vitamin K as a main actor. It has been discovered that vitamin K is an essential cofactor for the activation of matrix Gla protein (MGP), a calcification inhibitor in the vessel wall. Patients with CKD often suffer from vitamin K deficiency, resulting in low active MGP and eventually a lack of inhibition of vascular calcification. Vitamin K supplementation and switching warfarin to new oral anticoagulants are potential treatments. In addition, MGP may have a role as a non-invasive biomarker for vascular calcification. PMID- 27254817 TI - Revealing hot executive function in children with motor coordination problems: What's the go? AB - Recent research suggests that children with Developmental Coordination Disorder (DCD) often show deficits in executive functioning (EF) and, more specifically, the ability to use inhibitory control in 'hot', emotionally rewarding contexts. This study optimized the assessment of sensitivity of children with DCD to emotionally significant stimuli by using easily discriminable emotional expressions in a go/no-go task. Thirty-six children (12 with DCD), aged 7 12years, completed an emotional go/no-go task in which neutral facial expressions were paired with either happy or sad ones. Each expression was used as both, a go and no-go target in different runs of the task. There were no group differences in omission errors; however, the DCD group made significantly more commission errors to happy no-go faces. The particular pattern of performance in DCD confirms earlier reports of (hot) EF deficits. Specifically, a problem of inhibitory control appears to underlie the atypical pattern of performance seen in DCD on both cold and hot EF tasks. Disrupted coupling between cognitive control and emotion processing networks, such as fronto-parietal and fronto striatal networks, may contribute to reduced inhibitory control in DCD. The implications for a broader theoretical account of DCD are discussed, as are implications for intervention. PMID- 27254818 TI - Generation of stable Chinese hamster ovary pools yielding antibody titers of up to 7.6 g/L using the piggyBac transposon system. AB - Chinese hamster ovary (CHO) cells remain the default production host for many biopharmaceutical drugs, particularly monoclonal antibodies (mAb). Production of gram and kilogram quantities of protein typically requires the generation of stable CHO clones. Unfortunately, this process takes several months, significantly slowing down the drug discovery and development process. Therefore, improved technologies are needed to accelerate biopharmaceutical drug discovery and final drug substance manufacturing. In this study, we describe the generation of stable CHO pools using the piggyBac transposon system. We evaluated the system using four model antibody molecules (3 mAbs and 1 bispecific Ab). Stable CHO pools were isolated in 7-12 days. Using a simple 16-day fed-batch process, we measured titers ranging from 2.3 to 7.6 g/L for the four model antibodies. This represented a 4- to 12-fold increase relative to the controls. Additionally, we isolated stable CHO clones. We found that the stable CHO clones isolated from the piggyBac transposon pools yielded titers two to threefold higher relative to the control clones. Taken together, these results suggest that stable CHO pool and clone generation can be significantly improved by using the piggyBac transposon system. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1301-1307, 2016. PMID- 27254819 TI - DDB1 and CUL4 associated factor 11 (DCAF11) mediates degradation of Stem-loop binding protein at the end of S phase. AB - In eukaryotes, bulk histone expression occurs in the S phase of the cell cycle. This highly conserved system is crucial for genomic stability and proper gene expression. In metazoans, Stem-loop binding protein (SLBP), which binds to 3' ends of canonical histone mRNAs, is a key factor in histone biosynthesis. SLBP is mainly expressed in S phase and this is a major mechanism to limit bulk histone production to the S phase. At the end of S phase, SLBP is rapidly degraded by proteasome, depending on two phosphorylations on Thr 60 and Thr 61. Previously, we showed that SLBP fragment (aa 51-108) fused to GST, is sufficient to mimic the late S phase (S/G2) degradation of SLBP. Here, using this fusion protein as bait, we performed pull-down experiments and found that DCAF11, which is a substrate receptor of CRL4 complexes, binds to the phosphorylated SLBP fragment. We further confirmed the interaction of full-length SLBP with DCAF11 and Cul4A by co immunoprecipitation experiments. We also showed that DCAF11 cannot bind to the Thr61/Ala mutant SLBP, which is not degraded at the end of S phase. Using ectopic expression and siRNA experiments, we demonstrated that SLBP expression is inversely correlated with DCAF11 levels, consistent with the model that DCAF11 mediates SLBP degradation. Finally, we found that ectopic expression of the S/G2 stable mutant SLBP (Thr61/Ala) is significantly more toxic to the cells, in comparison to wild type SLBP. Overall, we concluded that CRL4-DCAF11 mediates the degradation of SLBP at the end of S phase and this degradation is essential for the viability of cells. PMID- 27254820 TI - Allocating responsibility for environmental risks: A comparative analysis of examples from water governance. AB - The focus of the present study is on the allocation of responsibilities for addressing environmental risks in transboundary water governance. Effective environmental management in transboundary situations requires coordinated and cooperative action among diverse individuals and organizations. Currently, little insight exists on how to foster collective action such that individuals and organizations take the responsibility to address transboundary environmental risks. On the basis of 4 cases of transboundary water governance, it will be shown how certain allocation principles are more likely to encourage cooperative action. The main lesson from these case studies is that the allocation of responsibilities should be seen as a risk distribution problem, including considerations of effectiveness, efficiency, and fairness. Integr Environ Assess Manag 2017;13:371-375. (c) 2016 SETAC. PMID- 27254822 TI - Enhanced Intrinsic Catalytic Activity of lambda-MnO2 by Electrochemical Tuning and Oxygen Vacancy Generation. AB - Chemically prepared lambda-MnO2 has not been intensively studied as a material for metal-air batteries, fuel cells, or supercapacitors because of their relatively poor electrochemical properties compared to alpha- and delta-MnO2 . Herein, through the electrochemical removal of lithium from LiMn2 O4 , highly crystalline lambda-MnO2 was prepared as an efficient electrocatalyst for the oxygen reduction reaction (ORR). The ORR activity of the material was further improved by introducing oxygen vacancies (OVs) that could be achieved by increasing the calcination temperature during LiMn2 O4 synthesis; a concentration of oxygen vacancies in LiMn2 O4 could be characterized by its voltage profile as the cathode in a lithiun-metal half-cell. lambda-MnO2-z prepared with the highest OV exhibited the highest diffusion-limited ORR current (5.5 mA cm(-2) ) among a series of lambda-MnO2-z electrocatalysts. Furthermore, the number of transferred electrons (n) involved in the ORR was >3.8, indicating a dominant quasi-4 electron pathway. Interestingly, the catalytic performances of the samples were not a function of their surface areas, and instead depended on the concentration of OVs, indicating enhancement in the intrinsic catalytic activity of lambda-MnO2 by the generation of OVs. This study demonstrates that differences in the electrochemical behavior of lambda-MnO2 depend on the preparation method and provides a mechanism for a unique catalytic behavior of cubic lambda-MnO2 . PMID- 27254821 TI - Cotesia vestalis teratocytes express a diversity of genes and exhibit novel immune functions in parasitism. AB - Some endoparasitoid wasps lay eggs that produce cells called teratocytes. In this study, we sequenced and analyzed the transcriptome of teratocytes from the solitary endoparasitoid Cotesia vestalis (Braconidae), which parasitizes larval stage Plutella xylostella (Plutellidae). Results identified many teratocyte transcripts with potential functions in affecting host immune defenses, growth or metabolism. Characterization of teratocyte-secreted venom-like protein 8 (TSVP-8) indicated it inhibits melanization of host hemolymph in vitro, while two predicted anti-microbial peptides (CvT-def 1 and 3) inhibited the growth of bacteria. Results also showed the parasitized hosts lacking teratocytes experienced higher mortality after immune challenge by pathogens than hosts with teratocytes. Taken together, these findings indicate that C. vestalis teratocytes secrete products that alter host immune functions while also producing anti microbial peptides with functions that help protect the host from infection by other organisms. PMID- 27254823 TI - Child and Adolescent Development in Latin America: Introduction to the Special Issue. PMID- 27254824 TI - Childhood Poverty and Cognitive Development in Latin America in the 21st Century. AB - For at least eight decades, researchers have analyzed the association between childhood poverty and cognitive development in different societies worldwide, but few of such studies have been carried out in Latin America. The aim of the present paper is to systematically review the empirical studies that have analyzed the associations between poverty and cognitive development in children under 18 years of age from Latin American and Caribbean countries between 2000 and 2015. This analysis takes into consideration the country where the work was conducted, the experimental and analytical design, sample size and composition, cognitive and poverty paradigms implemented, levels of analysis, and the inclusion of mediation analyses. Through these, we identify common patterns in the negative impact of poverty that have been repeatedly verified in the literature in other continents; we also call attention to a set of issues regarding sample, design, paradigms, impact, and mediation analyses that should be considered in future studies in the region. PMID- 27254825 TI - School Readiness Research in Latin America: Findings and Challenges. AB - Educational results in Latin America (LA) are well below those of developed countries. One factor that influences how well children do at school is school readiness. In this article, we review studies conducted in LA on the readiness skills of preschool children. We begin by discussing contextual factors that affect what is expected of children upon school entry, and we examine critical aspects of children's developmental contexts in LA. We then review local research on the level and determinants of three readiness skills of preschoolers in LA. Few studies allow comparisons between LA and other regions, but some results suggest that the oral language of children in LA before school entry is lower than in developed countries. These entry-level differences do not seem large enough to explain the poor educational results obtained by children in LA. We conclude regarding research needed to explain educational results and to inform educational policies. PMID- 27254826 TI - Adolescent Peer Relations and Socioemotional Development in Latin America: Translating International Theory into Local Research. AB - Peer relations constitute a main developmental context for adolescents. Peers offer an instance for identity definition and set the norms of acceptable and valued characteristics, behaviors, and attitudes, representing a societal model that allows and restrains avenues for adolescents' socioemotional development. The present article departs from these considerations to review research on adolescents' peer relations in Latin America from a socioemotional perspective. First, approaches to adolescence are discussed, with a main focus on attachment and identity theories, based on a bioecological framework. Then, a review of research in Latin America on friendships, school climate, and intergroup relations is presented. The discussion addresses the tension between theories and evidence generated in developed societies and highlights the particularities of Latin American youth, stressing the need for collecting local data. PMID- 27254827 TI - Computational Tracking of Mental Health in Youth: Latin American Contributions to a Low-Cost and Effective Solution for Early Psychiatric Diagnosis. AB - The early onset of mental disorders can lead to serious cognitive damage, and timely interventions are needed in order to prevent them. In patients of low socioeconomic status, as is common in Latin America, it can be hard to identify children at risk. Here, we briefly introduce the problem by reviewing the scarce epidemiological data from Latin America regarding the onset of mental disorders, and discussing the difficulties associated with early diagnosis. Then we present computational psychiatry, a new field to which we and other Latin American researchers have contributed methods particularly relevant for the quantitative investigation of psychopathologies manifested during childhood. We focus on new technologies that help to identify mental disease and provide prodromal evaluation, so as to promote early differential diagnosis and intervention. To conclude, we discuss the application of these methods to clinical and educational practice. A comprehensive and quantitative characterization of verbal behavior in children, from hospitals and laboratories to homes and schools, may lead to more effective pedagogical and medical intervention. PMID- 27254828 TI - Reading Comprehension in Latin America: Difficulties and Possible Interventions. AB - Reading comprehension (RC) is below the international standard in many countries of Latin America (LA). Here we review factors that might be associated with failure in RC of the first language in LA. Then we present interventions reporting beneficial impact on RC in typically developing students from English speaking countries and discuss their possible applicability in LA. We conclude that research-based pedagogical interventions are currently available to promote RC at school and may be suitable to implement in LA in order to improve RC. PMID- 27254829 TI - What Do We Know About the Development of Creativity in South America? AB - We review recent research about the development of creativity in South America focusing on studies of individual differences in creativity and educational and developmental studies of children and adolescents' creativity. Most South American researchers are influenced by mainstream psychometric approaches, although computational and cultural approaches are also considered. Two main areas of inquiry are: (a) the relationship between creativity and other constructs, and (b) the structural and cultural inhibitors of creativity in school. Studies conducted beyond the school shed light on the role resilience has in fostering creativity. The lack of studies testing interventions aimed at promoting creativity is concerning. There is also a surprising lack of observational studies related to the pedagogy of creativity. Last but not least, there is a need to advance research on other factors, in addition to the educational ones, that may play a role in fostering creativity in South America. PMID- 27254830 TI - Research on Child and Adolescent Development and Public Policy in Latin America. AB - This commentary discusses the implication of child and adolescent development research for public policy in Latin America. As illustrated by the articles in this special issue, even though the research of child and adolescent development in Latin America is making significant progress, still more research is needed. Developmental research in the region faces the challenge of uncovering the mechanisms that affect child development in a context of high levels of poverty and inequality. In addition, researchers in the region should be particularly careful in using appropriate and rigorous methods, improving the design and adaptation of instruments that measure child and adolescent development, developing longitudinal datasets, and looking for causal evidence. Children and adolescents in Latin America will benefit from a further expansion of developmental research. Research in child and adolescent development using data from Latin America can advise policy makers and help improve the design and evaluation of interventions and public policies that promote child and adolescent well-being in the region. PMID- 27254831 TI - Synthesis of Two-Dimensional Materials for Capacitive Energy Storage. AB - The unique properties and great variety of two-dimensional (2D) nanomaterials make them highly attractive for energy storage applications. Here, an insight into the progress made towards the application of 2D nanomaterials for capacitive energy storage is provided. Synthesis methods, and electrochemical performance of various classes of 2D nanomaterials, particularly based on graphene, transition metal oxides, dichalcogenides, and carbides, are presented. The factors that directly influence capacitive performance are discussed throughout the text and include nanosheet composition, morphology and texture, electrode architecture, and device configuration. Recent progress in the fabrication of 2D-nanomaterials based microsupercapacitors and flexible and free-standing supercapacitors is presented. The main electrode manufacturing techniques with emphasis on scalability and cost-effectiveness are discussed, and include laser scribing, printing, and roll-to-roll manufacture. Various issues that prevent the use of the full energy-storage potential of 2D nanomaterials and how they have been tackled are discussed, and include nanosheet aggregation and the low electrical conductivity of some 2D nanomaterials. Particularly, the design of hybrid and hierarchical 2D and 3D structures based on 2D nanomaterials is presented. Other challenges and opportunities are discussed and include: control of nanosheets size and thickness, chemical and electrochemical instability, and scale-up of electrode films. PMID- 27254832 TI - Alteration of the Nonsystemic Behavior of the Pesticide Ferbam on Tea Leaves by Engineered Gold Nanoparticles. AB - A model system consisting of a nonsystemic pesticide (ferbam), engineered gold nanoparticles (AuNPs) and a plant tissue (tea leaves) was investigated using surface enhanced Raman spectroscopy (SERS). Ferbam has no ability by itself to penetrate into tea leaves. When AuNPs were placed with ferbam onto the surface of tea leaves, however, the SERS signal of the ferbam-AuNPs complex was observed inside of the tea leaves. Within 1 h, the ferbam-AuNPs complex rapidly penetrated into the leaf to a depth of approximately 190 MUm, about (1)/3 to (1)/2 of the leaf's thickness. The rate of penetration was dependent on the size of AuNPs, with 30 nm AuNPs-ferbam penetrating more rapidly when compared with complexes made with the 50 and 69 nm AuNPs. These results clearly demonstrated an alteration of the nonsystemic behavior of ferbam in the combined presence with AuNPs. This finding might lead to the development of some new pesticide formulations. Conversely, new toxicity issues may arise as the behaviors and fate of pesticides are altered significantly upon interaction with engineered NPs in the pesticide formulation or environment. PMID- 27254833 TI - Small-angle scattering and 3D structure interpretation. AB - This review focuses on advances in the application of solution small-angle scattering (SAS) in structural analysis of biomolecules and the complexes they form. Examples highlighted illustrate the unique contribution of SAS, using both X-rays and neutrons, in hybrid or integrative modelling methods. The increased information content when neutron scattering with contrast variation is used is a particular focus. Finally, progress toward an agreed reporting framework, the development of open data and model archives, and the importance of these initiatives is covered. PMID- 27254834 TI - An unsuspected cause of abdominal pain and fever: lost gallstone-related perisplenic abscess. PMID- 27254835 TI - Zika Virus, Microcephaly, and Ocular Findings. PMID- 27254836 TI - Foot Rollover Temporal Parameters During Straight-Ahead and Side-Cut Walking in Obese and Nonobese Postmenopausal Women. AB - The purpose of this study was to compare the temporal foot rollover data between straight-ahead and side-cut walking and to establish a reference dataset for obese and nonobese postmenopausal women. Pressure data were collected using the two-step protocol. The initial, final, and duration of contact of 10 foot areas were measured, as 5 instants and 4 phases. Significant temporal foot rollover differences were found during walking with and without directional changes; however, most of these differences were common for obese and nonobese subjects.The trailing limb during the side-cut task anticipated the initial and final contact of the lateral forefoot and increased midfoot and toes duration, suggesting a greater role of these areas in the initial break and in foot stability. The leading limb throughout the side-cut task exhibited longer duration of the heel, midfoot, and stance phase probably due to an increase in the stride length of the trailing limb and leaning of the trunk toward the inner side of the turn. Additionally, obese women revealed a later final contact and longer contact duration of some metatarsal areas suggesting that the greater inertia of these subjects demands more time to stabilize and prepare the foot for the next step. Please provide 3 to 5 keywords for the article. PMID- 27254837 TI - Incidence and mortality of gynaecological cancers: Secular trends in urban Shanghai, China over 40 years. AB - AIM: Appraisal of cancer trends is essential for future cancer control, but relevant studies in China are scarce due to a lack of long-term data. With 40 years of cancer registry data, we sought to evaluate secular time trends in incidence and mortality of gynaecological cancers in an urban Chinese population. MATERIALS AND METHODS: Data on incidence and mortality of invasive cervical, uterine and ovarian cancer were collected by the Shanghai Cancer Registry. Age standardised incidence and mortality rates were calculated for women aged 20-84 in urban Shanghai between 1973 and 2012. Age-period-cohort Poisson regression models were used to evaluate age, period and cohort effects. Overall linear trends, interpreted as the estimated annual percentage change (EAPC), were derived from the net drift in age-drift models. RESULTS: Overall, cervical cancer incidence and mortality substantially decreased (EAPC = -4.5% and -5.5%, respectively); however, an upward trend was apparent among younger women (age <60). Uterine cancer incidence increased slightly (EAPC = 1.8%), while mortality decreased over time (EAPC = -2.4%). Ovarian cancer incidence and mortality both increased, although the increase in incidence (EAPC = 1.8%) was larger than mortality (EAPC = 0.6%). While cohort effects were most evident for cervical cancer incidence and mortality, significant age, period, and cohort effects were found for all three gynaecological cancers evaluated. CONCLUSIONS: These secular trends in incidence and mortality of gynaecological cancers in Shanghai likely reflect changing risk factor profiles and improved cancer prognosis over time, and suggest new priorities and call for additional efforts for gynaecological cancer prevention and control for women in China. PMID- 27254839 TI - Marijuana Use in Youth from Bench to Bedside to Longitudinal Outlook. PMID- 27254838 TI - Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer. AB - Primary treatment of rectal cancer was the focus of the second St. Gallen European Organisation for Research and Treatment of Cancer (EORTC) Gastrointestinal Cancer Conference. In the context of the conference, a multidisciplinary international expert panel discussed and voted on controversial issues which could not be easily answered using published evidence. Main topics included optimal pretherapeutic imaging, indication and type of neoadjuvant treatment, and the treatment strategies in advanced tumours. Here we report the key recommendations and summarise the related evidence. The treatment strategy for localised rectal cancer varies from local excision in early tumours to neoadjuvant radiochemotherapy (RCT) in combination with extended surgery in locally advanced disease. Optimal pretherapeutic staging is a key to any treatment decision. The panel recommended magnetic resonance imaging (MRI) or MRI + endoscopic ultrasonography (EUS) as mandatory staging modalities, except for early T1 cancers with an option for local excision, where EUS in addition to MRI was considered to be most important because of its superior near-field resolution. Primary surgery with total mesorectal excision was recommended by most panellists for some early tumours with limited risk of recurrence (i.e. cT1 2 or cT3a N0 with clear mesorectal fascia on MRI and clearly above the levator muscles), whereas all other stages were considered for multimodal treatment. The consensus panel recommended long-course RCT over short-course radiotherapy for most clinical situations where neoadjuvant treatment is indicated, with the exception of T3a/b N0 tumours where short-course radiotherapy or even no neoadjuvant therapy were regarded to be an option. In patients with potentially resectable tumours and synchronous liver metastases, most panel members did not see an indication to start with classical fluoropyrimidine-based RCT but rather favoured preoperative short-course radiotherapy with systemic combination chemotherapy or alternatively a liver-first resection approach in resectable metastases, which both allow optimal systemic therapy for the metastatic disease. In general, proper patient selection and discussion in an experienced multidisciplinary team was considered as crucial component of care. PMID- 27254840 TI - Cannabis Use in Adolescence and Young Adulthood: A Review of Findings from the Victorian Adolescent Health Cohort Study. AB - The Victorian Adolescent Health Cohort Study (VAHCS) is a long-term Australian cohort study that has documented cannabis use in young Australians from the mid teens to the mid-30s. The study findings have described the natural history of early cannabis use, remission, and escalation and the social and mental health consequences of different patterns of use. The adverse consequences of cannabis use are most clear-cut in heavy early adolescent users. These consequences include educational failure, persisting mental health problems, and progression to other substance use. For later onset and occasional users, the risks are lower and appear to entail modest elevations in risk for other drug use compared with never users. With growing evidence of health consequences, there is a strong case for actions around early heavy adolescent users. Prevention of early use, identification and treatment of early heavy users, and harm reduction through diversion of early heavy users away from the custodial justice system into health care are all priority responses. PMID- 27254842 TI - The "Vulnerability" of Psychiatric Research Participants: Why This Research Ethics Concept Needs to Be Revisited. PMID- 27254841 TI - What Can Rats Tell Us about Adolescent Cannabis Exposure? Insights from Preclinical Research. AB - Marijuana is the most widely used drug of abuse among adolescents. Adolescence is a vulnerable period for brain development, during which time various neurotransmitter systems such as the glutamatergic, GABAergic, dopaminergic, and endocannabinoid systems undergo extensive reorganization to support the maturation of the central nervous system (CNS). ?-9-tetrahydrocannabinol (THC), the psychoactive component of marijuana, acts as a partial agonist of CB1 cannabinoid receptors (CB1Rs). CB1Rs are abundant in the CNS and are central components of the neurodevelopmental changes that occur during adolescence. Thus, overactivation of CB1Rs by cannabinoid exposure during adolescence has the ability to dramatically alter brain maturation, leading to persistent and enduring changes in adult cerebral function. Increasing preclinical evidence lends support to clinical evidence suggesting that chronic adolescent marijuana exposure may be associated with a higher risk for neuropsychiatric diseases, including schizophrenia. In this review, we present a broad overview of current neurobiological evidence regarding the long-term consequences of adolescent cannabinoid exposure on adult neuropsychiatric-like disorders. PMID- 27254843 TI - Ethno-Racial Variation in Recovery From Severe Mental Illness: A Qualitative Comparison. AB - OBJECTIVE: Purpose-driven studies examining the relationship between ethnicity, culture, and recovery are absent from the empirical literature. As such, the overall aim of this study was to examine ethno-racial variations in recovery perspectives. Specific objectives consist of comparing and contrasting ethno racial variations in 1) definitions of recovery, 2) barriers to recovery, and 3) facilitators of recovery. METHODS: We recruited people with severe mental illness from 2 broad ethno-racial groups (Caribbean-Canadian and Euro-Canadian) to partake in a qualitative interview on recovery (n = 47). Participants were asked to give their own definitions of recovery, as well as self-perceived barriers and facilitators. Interview transcripts were then subjected to thematic analysis. We compared and contrasted the distribution and salience of emerging themes between the Euro-Canadian and Caribbean-Canadian participants. RESULTS: Recovery was consistently defined as a gradual process involving progress in key life domains including employment, social engagement, and community participation by both groups. This was underpinned by a growing future orientation. Stigma, financial strain, and psychiatric hospitalization were considered major barriers to recovery in both groups. Participants from both groups generally considered stated definitions of recovery to be simultaneous facilitators of recovery employment and social engagement being the most frequently mentioned. God and religion were key facilitators for the Caribbean-Canadian group but not for Euro Canadians. CONCLUSIONS: Definitions, barriers, and facilitators to recovery were generally shared among our sample, regardless of ethno-racial status, with the exception of God and religion. PMID- 27254844 TI - Military Occupational Outcomes in Canadian Armed Forces Personnel with and without Deployment-Related Mental Disorders. AB - OBJECTIVE: Mental disorders are common in military organizations, and these frequently lead to functional impairments that can interfere with duties and lead to costly attrition. In Canada, the military mental health system has received heavy investment to improve occupational outcomes. We investigated military occupational outcomes of diagnosed mental disorders in a cohort of 30,513 personnel who deployed on the Afghanistan mission. METHODS: Cohort members were military personnel who deployed on the Afghanistan mission from 2001 to 2008. Mental disorder diagnoses and their attribution to the Afghanistan mission were ascertained via medical records in a stratified random sample (n = 2014). Career limiting medical conditions (that is, condition-associated restrictions that reliably lead to medically related attrition) were determined using administrative data. Outcomes were assessed from first Afghanistan-related deployment return. RESULTS: At 5 years of follow-up, the Kaplan-Meier estimated cumulative fraction with career-limiting medical conditions was 40.9% (95% confidence interval [CI] 35.5 to 46.4) among individuals with Afghanistan service related mental disorders (ARMD), 23.6% (CI 15.5 to 31.8) with other mental disorders, and 11.1% (CI 8.9 to 13.3) without mental disorders. The adjusted Cox regression hazard ratios for career-limiting medical condition risk were 4.89 (CI 3.85 to 6.23) among individuals with ARMD and 2.31 (CI 1.48 to 3.60) with other mental disorders, relative to those without mental disorders. CONCLUSIONS: Notwithstanding the Canadian military's mental health system investments, mental disorders (particularly ARMD) still led to a high risk of adverse military occupational outcomes. Such investments have intrinsic value but may not translate into reduced medically related attrition without improvements in prevention and treatment effectiveness. PMID- 27254845 TI - Rates of Mental Illness and Addiction among High-Cost Users of Medical Services in Ontario. AB - OBJECTIVE: To quantify the burden of mental illness and addiction among high costing users of medical services (HCUs) using population-level data from Ontario, and compare to a referent group of nonusers. METHOD: We conducted a population-level cohort study using health administrative data from fiscal year 2011-2012 for all Ontarians with valid health insurance as of April 1, 2011 (N = 10,909,351). Individuals were grouped based on medical costs for hospital, emergency, home, complex continuing, and rehabilitation care in 2011-2012: top 1%, top 2% to 5%, top 6% to 50%, bottom 50%, and a zero-cost nonuser group. The rate of diagnosed psychotic, major mood, and substance use disorders in each group was compared to the zero-cost referent group with adjusted odds ratios (AORs) for age, sex, and socioeconomic status. A sensitivity analysis included anxiety and other disorders. RESULTS: Mental illness and addiction rates increased across cost groups affecting 17.0% of the top 1% of users versus 5.7% of the zero-cost group (AOR, 3.70; 95% confidence interval [CI], 3.59 to 3.81). This finding was most pronounced for psychotic disorders (3.7% vs. 0.7%; AOR, 5.07; 95% CI, 4.77 to 5.38) and persisted for mood disorders (10.0% vs. 3.3%; AOR, 3.52; 95% CI, 3.39 to 3.66) and substance use disorders (7.0% vs. 2.3%; AOR, 3.82; 95% CI, 3.66 to 3.99). When anxiety and other disorders were included, the rate of mental illness was 39.3% in the top 1% compared to 21.3% (AOR, 2.39; 95% CI, 2.34 to 2.45). CONCLUSIONS: A high burden of mental illness and addiction among HCUs warrants its consideration in the design and delivery of services targeting HCUs. PMID- 27254849 TI - Parental Perception of Neighborhood Safety and Children's Physical Activity. AB - BACKGROUND: We examined the relationship between parents' perception of neighborhood safety and children's physical activity and use of recreation facilities in a US nationally representative sample of fifth grade children. METHODS: We used data from the Early Childhood Longitudinal Study Kindergarten cohort, fifth grade sample (N = 9827). Multivariate logistic and linear regression models were used to examine associations between parents' perception of neighborhood safety for outside play and number of days children engage in physical activity, as well as children's use of recreational facilities for physical activity. RESULTS: Children who used recreational facilities engaged in physical activity on more days of the week compared with children who did not use a facility (3.3 days vs. 3.8 days, P < .0001). Children from neighborhoods perceived as unsafe by parents engaged in almost 1 less day per week in physical activity (beta = -.89, P < .0001). Children from neighborhoods perceived as unsafe were less likely to use recreational facilities compared with children from neighborhoods perceived as safe (odds ratio = 0.72, P < .0001). Children from less affluent families across rural and urban areas had half the odds of using recreational facilities compared with children from the wealthiest families living in urban areas. CONCLUSIONS: Parents' perception of neighborhood safety for outside play can deter or promote children's physical activity and use of recreational facilities. Children from less affluent families are less likely to use facilities than children from wealthy families, regardless of place of residence. PMID- 27254846 TI - Psychosocial Interventions in Reducing Cannabis Use in Early Phase Psychosis: A Canadian Survey of Treatments Offered. AB - OBJECTIVE: Cannabis use in people with early phase psychosis (EPP) can have a significant impact on long-term outcomes. The purpose of this investigation was to describe current cannabis use treatment practices in English-speaking early intervention services (EISs) in Canada and determine if their services are informed by available evidence. METHOD: Thirty-five Canadian English-speaking EISs for psychosis were approached to complete a survey through email, facsimile, or online in order to collect information regarding their current cannabis use treatment practices. RESULTS: Data were acquired from 27 of the 35 (78%) programs approached. Only 12% of EISs offered formal services that targeted cannabis use, whereas the majority (63%) of EISs offered informal services for all substance use, not specifically cannabis. In programs with informal services, individual patient psychoeducation (86%) was slightly more common than individual motivational interviewing (MI) (76%) followed by group patient psychoeducation (52%) and information handouts (52%). Thirty-seven percent of EISs offered formal services for substance use, and compared to programs with informal services, more MI, cognitive-behavioural therapy, and family services were offered, with individual treatment modalities more common than groups. No EISs used contingency management, even though it has some preliminary evidence in chronic populations. Evidence-based service implementation barriers included appropriate training and administrative support. CONCLUSIONS: While most English-speaking Canadian EIS programs offer individual MI and psychoeducation, which is in line with the available literature, there is room for improvement in cannabis treatment services based on current evidence for both people with EPP and their families. PMID- 27254850 TI - The Stress-Metabolic Syndrome Relationship in Adolescents: An Examination of the Moderating Potential of Physical Activity. AB - BACKGROUND: The role of psychosocial stress in the development of obesity and metabolic syndrome is receiving increased attention and has led to examination of whether physical activity may moderate the stress-metabolic syndrome relationship. The current study examined relationships among physical activity, stress, and metabolic syndrome in adolescents. METHODS: Participants (N = 126; 57 girls, 69 boys) were assessed for anthropometry, psychosocial stress, physical activity, and metabolic syndrome variables; t tests were used to examine sex differences, and regression analysis was used to assess relationships among variables controlling for sex and maturity status. RESULTS: Mean body mass index approached the 75th percentile for both sexes. Typical sex differences were observed for systolic blood pressure, time spent in moderate and vigorous physical activity, and perceived stress. Although stress was not associated with MetS (beta = -.001, P = .82), a modest, positive relationship was observed with BMI (beta = .20, P = .04). CONCLUSIONS: Strong relationships between physical activity and stress with MetS or BMI were not found in this sample. Results may be partially explained by overall good physical health status of the participants. Additional research in groups exhibiting varying degrees of health is needed. PMID- 27254851 TI - Objectively Assessed Physical Activity and Associated Factors Among Adults in Peri-Urban and Rural Eastern Uganda: A Population-based Study. AB - BACKGROUND: Data on physical inactivity, a known risk factor for noncommunicable diseases and its correlates in sub-Saharan Africa are almost absent. We assessed physical activity patterns and associated factors among adults. METHODS: A populationbased study of 1208 adults was conducted in the Iganga-Mayuge Health and Demographic Surveillance Site, Uganda. Physical activity was assessed using a pedometer for 7 days. Physical inactivity was defined as a daily average of < 7500 steps while sedentary behavior was defined as a daily average of < 5000 steps. Logistic regression was conducted to identify factors associated with physical inactivity and sedentary behavior. RESULTS: Of the 1208 participants, 18.8% were sedentary (10.6% of men; 26.9% of women, P < .001), 37.6% were physically inactive (28.5% of men; 46.6% of women, P < .001). Factors associated with sedentary behavior were being female, >= 65 years, peri-urban residence, being a domestic worker, formal employment and lower primary education. Factors associated with physical inactivity were being female, 55 to 64 years, >= 65 years, peri-urban residence, overweight and obesity. CONCLUSIONS: Sedentary behavior and physical inactivity were prevalent among the adult population. Targeted physical activity promotion interventions are needed. PMID- 27254852 TI - Erratum to "Extracting Information From Previous Full-Dose CT Scan for Knowledge Based Bayesian Reconstruction of Current Low-Dose CT Images". AB - Advertisement, IEEE. PMID- 27254853 TI - Leisure-Time and Occupational Physical Activity in Early and Late Adulthood in Relation to Later Life Physical Functioning. AB - BACKGROUND: Physical activity (PA) has beneficial effects on older age physical functioning, but longitudinal studies with follow-ups extending up to decades are few. We investigated the association between leisure-time PA (LTPA) and occupational PA (OPA) from early to late adulthood in relation to later life performance-based physical functioning. METHODS: The study involved 1260 people aged 60 to 79 years who took part in assessments of physical functioning (Short Physical Performance Battery [SPPB] test, 10-m maximal walking test, and grip strength test). Participants' data on earlier life LTPA/OPA (age range 25 to 74 years) were received from the previous studies (average follow-up 13.4 years). Logistic, linear, and censored regression models were used to assess the associations between LTPA/OPA earlier in life and subsequent physical functioning. RESULTS: A high level of LTPA earlier in life was associated with a lower risk of having difficulties on the SPPB test (odds ratio [OR]: 0.37; 95% confidence interval [CI], 0.24-0.58) and especially on the chair rise test (OR: 0.42; 95% CI, 0.27-0.64) in old age. Heavy manual work predicted difficulties on SPPB (OR: 1.91; 95% CI, 1.22-2.98) and the chair rise test (OR: 1.75; 95% CI, 1.14-2.69) and poorer walking speed (beta = .10, P = .005). CONCLUSIONS: This study highlights the importance of LTPA on later life functioning, but also indicates the inverse effects that may be caused by heavy manual work. PMID- 27254855 TI - Drowsiness Detection by Bayesian-Copula Discriminant Classifier Based on EEG Signals During Daytime Short Nap. AB - OBJECTIVE: Daytime short nap involves individual physiological states including alertness and drowsiness. In order to have a better understanding of the periodical rhymes of physiological states and then promote a good interpretability of alertness, the aim of this study is to detect drowsiness during daytime short nap. METHODS: A method of Bayesian-copula discriminant classifier (BCDC) was introduced to detect individual drowsiness based on the physiological features extracted from electroencephalogram (EEG) signals. As an extension of traditional Bayesian decision theory, the BCDC method tries to construct the class-conditional probability density functions by exploiting the theory of copula and kernel density estimation. RESULTS: The proposed BCDC method was validated with experimental dataset and compared with other traditional methods for drowsiness detection. The obtained results showed that our method outperformed other methods in terms of three evaluation criteria. CONCLUSION: Our proposed method is effective to detect drowsiness with superior performance. Additionally, the BCDC method is relatively robust to different parameter settings on the group-level dataset. SIGNIFICANCE: The proposed method is likely to be a useful tool to improve the correctness of the estimated class-conditional probability density functions. Since features are extracted from spontaneous EEG recordings, the results of this study can be further generalized to other experimental environment to detect vigilance level or driver drowsiness. PMID- 27254858 TI - An Efficient Multilinear Optimization Framework for Hypergraph Matching. AB - Hypergraph matching has recently become a popular approach for solving correspondence problems in computer vision as it allows the use of higher-order geometric information. Hypergraph matching can be formulated as a third-order optimization problem subject to assignment constraints which turns out to be NP hard. In recent work, we have proposed an algorithm for hypergraph matching which first lifts the third-order problem to a fourth-order problem and then solves the fourth-order problem via optimization of the corresponding multilinear form. This leads to a tensor block coordinate ascent scheme which has the guarantee of providing monotonic ascent in the original matching score function and leads to state-of-the-art performance both in terms of achieved matching score and accuracy. In this paper we show that the lifting step to a fourth-order problem can be avoided yielding a third-order scheme with the same guarantees and performance but being two times faster. Moreover, we introduce a homotopy type method which further improves the performance. PMID- 27254856 TI - Evaluation of Six Registration Methods for the Human Abdomen on Clinically Acquired CT. AB - OBJECTIVE: This work evaluates current 3-D image registration tools on clinically acquired abdominal computed tomography (CT) scans. METHODS: Thirteen abdominal organs were manually labeled on a set of 100 CT images, and the 100 labeled images (i.e., atlases) were pairwise registered based on intensity information with six registration tools (FSL, ANTS-CC, ANTS-QUICK-MI, IRTK, NIFTYREG, and DEEDS). The Dice similarity coefficient (DSC), mean surface distance, and Hausdorff distance were calculated on the registered organs individually. Permutation tests and indifference-zone ranking were performed to examine the statistical and practical significance, respectively. RESULTS: The results suggest that DEEDS yielded the best registration performance. However, due to the overall low DSC values, and substantial portion of low-performing outliers, great care must be taken when image registration is used for local interpretation of abdominal CT. CONCLUSION: There is substantial room for improvement in image registration for abdominal CT. SIGNIFICANCE: All data and source code are available so that innovations in registration can be directly compared with the current generation of tools without excessive duplication of effort. PMID- 27254857 TI - Characterization of a Honeycomb-Like Scaffold With Dielectrophoresis-Based Patterning for Tissue Engineering. AB - OBJECTIVE: Seeding and patterning of cells with an engineered scaffold is a critical process in artificial tissue construction and regeneration. To date, many engineered scaffolds exhibit simple intrinsic designs, which fail to mimic the geometrical complexity of native tissues. In this study, a novel scaffold that can automatically seed cells into multilayer honeycomb patterns for bone tissue engineering application was designed and examined. METHODS: The scaffold incorporated dielectrophoresis for noncontact manipulation of cells and intrinsic honeycomb architectures were integrated in each scaffold layer. When a voltage was supplied to the stacked scaffold layers, three-dimensional electric fields were generated, thereby manipulating cells to form into honeycomb-like cellular patterns for subsequent culture. RESULTS: The biocompatibility of the scaffold material was confirmed through the cell viability test. Experiments were conducted to evaluate the cell viability during DEP patterning at different voltage amplitudes, frequencies, and manipulating time. Three different mammalian cells were examined and the effects of the cell size and the cell concentration on the resultant cellular patterns were evaluated. CONCLUSION: Results showed that the proposed scaffold structure was able to construct multilayer honeycomb cellular patterns in a manner similar to the natural tissue. SIGNIFICANCE: This honeycomb-like scaffold and the dielectrophoresis-based patterning technique examined in this study could provide the field with a promising tool to enhance seeding and patterning of a wide range of cells for the development of high quality artificial tissues. PMID- 27254859 TI - Modeling 4D Human-Object Interactions for Joint Event Segmentation, Recognition, and Object Localization. AB - In this paper, we present a 4D human-object interaction (4DHOI) model for solving three vision tasks jointly: i) event segmentation from a video sequence, ii) event recognition and parsing, and iii) contextual object localization. The 4DHOI model represents the geometric, temporal, and semantic relations in daily events involving human-object interactions. In 3D space, the interactions of human poses and contextual objects are modeled by semantic co-occurrence and geometric compatibility. On the time axis, the interactions are represented as a sequence of atomic event transitions with coherent objects. The 4DHOI model is a hierarchical spatial-temporal graph representation which can be used for inferring scene functionality and object affordance. The graph structures and parameters are learned using an ordered expectation maximization algorithm which mines the spatial-temporal structures of events from RGB-D video samples. Given an input RGB-D video, the inference is performed by a dynamic programming beam search algorithm which simultaneously carries out event segmentation, recognition, and object localization. We collected a large multiview RGB-D event dataset which contains 3,815 video sequences and 383,036 RGB-D frames captured by three RGB-D cameras. The experimental results on three challenging datasets demonstrate the strength of the proposed method. PMID- 27254860 TI - Learning Category-Specific Deformable 3D Models for Object Reconstruction. AB - We address the problem of fully automatic object localization and reconstruction from a single image. This is both a very challenging and very important problem which has, until recently, received limited attention due to difficulties in segmenting objects and predicting their poses. Here we leverage recent advances in learning convolutional networks for object detection and segmentation and introduce a complementary network for the task of camera viewpoint prediction. These predictors are very powerful, but still not perfect given the stringent requirements of shape reconstruction. Our main contribution is a new class of deformable 3D models that can be robustly fitted to images based on noisy pose and silhouette estimates computed upstream and that can be learned directly from 2D annotations available in object detection datasets. Our models capture top down information about the main global modes of shape variation within a class providing a "low-frequency" shape. In order to capture fine instance-specific shape details, we fuse it with a high-frequency component recovered from shading cues. A comprehensive quantitative analysis and ablation study on the PASCAL 3D+ dataset validates the approach as we show fully automatic reconstructions on PASCAL VOC as well as large improvements on the task of viewpoint prediction. PMID- 27254861 TI - An Air-Coupled Multiple Moving Membrane Micromachined Ultrasonic Transducer With Inverse Biasing Functionality. AB - A novel air-coupled multiple moving membrane-capacitive micromachined ultrasonic transducer ( [Formula: see text]-CMUT) with individually biased deflectable plates has been developed. Unlike the conventional capacitive micromachined ultrasonic transducer, this device cell structure includes an additional deflectable plate that is suspended underneath the transducer top plate. This added flexible plate contributes to the device signal transmission and reception. It is demonstrated that due to the presence of this added moving plate, the transducer is capable of operating under inverse bias condition, where the driving voltage is sandwiched between two grounded electrodes. COMSOL electromechanical simulations were conducted to investigate the influence of the transducer additional moving plate. A set of three individuals and an array of [Formula: see text]-CMUT transducers were fabricated using a sacrificial technique and with resonant frequencies ranging from 0.8 to 2.1 MHz. Electrical, optical, and pitch-catch acoustic measurements were performed to characterize the transducers properties under inverse bias condition. The experimental results are shown to be in good agreement with the simulation results for all of the fabricated transducers. It is shown that these transducers are fully functional under both normal and inverse bias conditions without any degradation in the transducer performance. PMID- 27254862 TI - Tissue Attenuation Estimation by Mean Frequency Downshift and Bandwidth Limitation. AB - Attenuation of ultrasound in tissue can be estimated from the propagating pulse center frequency downshift. This method assumes that the envelope of the emitted pulse can be approximated by a Gaussian function and that the attenuation linearly depends on frequency. The resulting downshift of the mean frequency depends not only on attenuation but also on pulse bandwidth and propagation distance. This kind of approach is valid for narrowband pulses and shallow penetration depth. However, for short pulses and deep penetration, the frequency downshift is rather large and the received spectra are modified by the limited bandwidth of the receiving system. In this paper, the modified formula modeling the mean frequency of backscattered echoes is presented. The equation takes into account the limitation of the bandwidth due to bandpass filtration of the received echoes. This approach was applied to simulate the variation of the mean frequency of the pulse propagating for both weakly and strongly attenuating media and for narrowband and wideband pulses. The behavior of both the standard and modified estimates of attenuation has been validated using RF data from a tissue mimicking phantom. The ultrasound attenuation of the phantom, determined with a corrected equation, was close to its true value, while the result obtained using the original formula was lower by as much as 50% at a depth of 8 cm. PMID- 27254863 TI - SAW Characteristics of AlN/SiO2/3C-SiC Layered Structure With Embedded Electrodes. AB - A layered structure of aluminum nitride (AlN)/silicon dioxide (SiO2)/cubic silicon carbide with embedded electrodes, which enables the growth of high quality AlN thin films, is proposed and studied. The phase velocity, coupling factor, and temperature coefficient of frequency (TCF) of surface acoustic waves in the proposed structure have been investigated using the finite-element method. The simulation results show that a high velocity of 5485 m/s and a large effective coupling factor ( K2) of 1.45% can be simultaneously obtained for the first mode. The dramatic enhanced K2 of 10.5% is also obtainable on the proposed structure employing Sc0.4Al0.6N thin film. Besides, the excellent zero TCF is also achieved without deteriorating the coupling factor by adding an amorphous SiO2 overlay. PMID- 27254864 TI - High-Temperature Dielectrics in BNT-BT-Based Solid Solution. AB - Bi0.5Na0.5TiO3-BaTiO3 (BNT-BT)-based ternary solid solutions were investigated for high-temperature capacitor applications. Through a comprehensive investigation of the (1 - x )(0.92Bi0.5Na0.5TiO3-0.08BaTiO3)- x NaNbO3 [(1 - x )(BNT-BT)- x NN, x = 0 -0.45] system, 0.85(BNT-BT)-0.15NN was selected as the parent matrix due to its relatively high permittivity (>1800) and favorable energy-storage density (0.56 J/cm3 at 7 kV/mm). The effect of bismuth substitution on the dielectric properties of the matrix was further characterized. The introduction of bismuth greatly broadened the operational temperature range of 0.85(BNT-BT)-0.15Na1-3yBiyNbO3 ceramics to over 327 degrees C for a +/-15% tolerance. The dc resistivities were of the order of 108 - [Formula: see text] magnitude from room temperature to 300 degrees C. An activation energy of 1.1-1.2 eV in 200-350 degrees C was obtained from dc resistivity data, suggesting that the conduction process in this temperature range may be associated with oxygen vacancy migration. Furthermore, the energy storage properties were largely improved by the addition of bismuth. When the substitution of Bi over Na achieved was up to 7%, the energy-storage density and efficiency reached 0.62 J/cm3 and 88% at 7 kV/mm, respectively. These results confirm that a BNT-BT-based solid solution is a promising candidate for lead-free high-temperature capacitor applications. PMID- 27254865 TI - Large Deformation Multiresolution Diffeomorphic Metric Mapping for Multiresolution Cortical Surfaces: A Coarse-to-Fine Approach. AB - Brain surface registration is an important tool for characterizing cortical anatomical variations and understanding their roles in normal cortical development and psychiatric diseases. However, surface registration remains challenging due to complicated cortical anatomy and its large differences across individuals. In this paper, we propose a fast coarse-to-fine algorithm for surface registration by adapting the large diffeomorphic deformation metric mapping (LDDMM) framework for surface mapping and show improvements in speed and accuracy via a multiresolution analysis of surface meshes and the construction of multiresolution diffeomorphic transformations. The proposed method constructs a family of multiresolution meshes that are used as natural sparse priors of the cortical morphology. At varying resolutions, these meshes act as anchor points where the parameterization of multiresolution deformation vector fields can be supported, allowing the construction of a bundle of multiresolution deformation fields, each originating from a different resolution. Using a coarse-to-fine approach, we show a potential reduction in computation cost along with improvements in sulcal alignment when compared with LDDMM surface mapping. PMID- 27254866 TI - Demosaicing Based on Directional Difference Regression and Efficient Regression Priors. AB - Color demosaicing is a key image processing step aiming to reconstruct the missing pixels from a recorded raw image. On the one hand, numerous interpolation methods focusing on spatial-spectral correlations have been proved very efficient, whereas they yield a poor image quality and strong visible artifacts. On the other hand, optimization strategies, such as learned simultaneous sparse coding and sparsity and adaptive principal component analysis-based algorithms, were shown to greatly improve image quality compared with that delivered by interpolation methods, but unfortunately are computationally heavy. In this paper, we propose efficient regression priors as a novel, fast post-processing algorithm that learns the regression priors offline from training data. We also propose an independent efficient demosaicing algorithm based on directional difference regression, and introduce its enhanced version based on fused regression. We achieve an image quality comparable to that of the state-of-the art methods for three benchmarks, while being order(s) of magnitude faster. PMID- 27254867 TI - Noise Power Spectrum Measurements in Digital Imaging With Gain Nonuniformity Correction. AB - The noise power spectrum (NPS) of an image sensor provides the spectral noise properties needed to evaluate sensor performance. Hence, measuring an accurate NPS is important. However, the fixed pattern noise from the sensor's nonuniform gain inflates the NPS, which is measured from images acquired by the sensor. Detrending the low-frequency fixed pattern is traditionally used to accurately measure NPS. However, detrending methods cannot remove high-frequency fixed patterns. In order to efficiently correct the fixed pattern noise, a gain correction technique based on the gain map can be used. The gain map is generated using the average of uniformly illuminated images without any objects. Increasing the number of images n for averaging can reduce the remaining photon noise in the gain map and yield accurate NPS values. However, for practical finite n , the photon noise also significantly inflates NPS. In this paper, a nonuniform-gain image formation model is proposed and the performance of the gain correction is theoretically analyzed in terms of the signal-to-noise ratio (SNR). It is shown that the SNR is O(?n) . An NPS measurement algorithm based on the gain map is then proposed for any given n . Under a weak nonuniform gain assumption, another measurement algorithm based on the image difference is also proposed. For real radiography image detectors, the proposed algorithms are compared with traditional detrending and subtraction methods, and it is shown that as few as two images ( n=1 ) can provide an accurate NPS because of the compensation constant (1+1/n) . PMID- 27254868 TI - Compression of 3D Point Clouds Using a Region-Adaptive Hierarchical Transform. AB - In free-viewpoint video, there is a recent trend to represent scene objects as solids rather than using multiple depth maps. Point clouds have been used in computer graphics for a long time, and with the recent possibility of real-time capturing and rendering, point clouds have been favored over meshes in order to save computation. Each point in the cloud is associated with its 3D position and its color. We devise a method to compress the colors in point clouds, which is based on a hierarchical transform and arithmetic coding. The transform is a hierarchical sub-band transform that resembles an adaptive variation of a Haar wavelet. The arithmetic encoding of the coefficients assumes Laplace distributions, one per sub-band. The Laplace parameter for each distribution is transmitted to the decoder using a custom method. The geometry of the point cloud is encoded using the well-established octtree scanning. Results show that the proposed solution performs comparably with the current state-of-the-art, while being much more computationally efficient. We believe this paper represents the state of the art in intra-frame compression of point clouds for real-time 3D video. PMID- 27254869 TI - Interactive High-Relief Reconstruction for Organic and Double-Sided Objects from a Photo. AB - We introduce an interactive user-driven method to reconstruct high-relief 3D geometry from a single photo. Particularly, we consider two novel but challenging reconstruction issues: i) common non-rigid objects whose shapes are organic rather than polyhedral/symmetric, and ii) double-sided structures, where front and back sides of some curvy object parts are revealed simultaneously on image. To address these issues, we develop a three-stage computational pipeline. First, we construct a 2.5D model from the input image by user-driven segmentation, automatic layering, and region completion, handling three common types of occlusion. Second, users can interactively mark-up slope and curvature cues on the image to guide our constrained optimization model to inflate and lift up the image layers. We provide real-time preview of the inflated geometry to allow interactive editing. Third, we stitch and optimize the inflated layers to produce a high-relief 3D model. Compared to previous work, we can generate high-relief geometry with large viewing angles, handle complex organic objects with multiple occluded regions and varying shape profiles, and reconstruct objects with double sided structures. Lastly, we demonstrate the applicability of our method on a wide variety of input images with human, animals, flowers, etc. PMID- 27254870 TI - A Parametric Simulation of Neuronal Noise From Microelectrode Recordings. AB - In this paper we present an efficient model of microelectrode recordings (MER) from the subthalamic nucleus acquired during deep brain stimulation (DBS) surgery. The model shows how changes in the "noise" relate to the neuronal spike time statistics. A top-down approach is used with analysis-by-synthesis of the MER power spectra. The model is built around a sum of filtered point processes consisting of thousands of neurons and including extracellular filtering. The quality of the model is demonstrated through comparisons to recordings from eight individuals (both hemispheres in six) who have undergone DBS implantation for the treatment of Parkinson's disease. The simulated recordings were compared using their voltage amplitude distributions, power spectral density estimates and phase synchrony while varying only one free parameter (the shape of the inter-spike interval distribution). Through this simple model, we show that the noise present in a DBS MER contains properties that match that of patient recordings when a Weibull distribution with shape parameter of 0.8 is used for the inter-spike interval. PMID- 27254871 TI - An Online Brain-Computer Interface Based on SSVEPs Measured From Non-Hair-Bearing Areas. AB - Steady state visual evoked potential (SSVEP)-based brain-computer interface (BCI) has gained a lot of attention due to its robustness and high information transfer rate (ITR). However, transitioning well-controlled laboratory-oriented BCI demonstrations to real-world applications poses severe challenges for this exciting field. For instance, conducting BCI experiments usually requires skilled technicians to abrade the area of skin underneath each electrode and apply an electrolytic gel or paste to acquire high-quality SSVEPs from hair-covered areas. Our previous proof-of-concept study has proposed an alternative approach that employed electroencephalographic signals collected from easily accessible non hair-bearing areas including neck, behind the ears, and face to realize an SSVEP based BCI. The study results showed that, with proper electrode placements and advanced signal-processing algorithms, the SSVEPs measured from non-hair-bearing areas in off-line SSVEP experiments could achieve comparable SNR to that obtained from the hair-bearing occipital areas. This study extended the previous work to systematically investigate the costs and benefits of non-hair SSVEPs. Furthermore, this study developed and evaluated an online BCI system based solely on non-hair EEG signals. A 12-target identification task was employed to quantitatively assess the performance of the online SSVEP-based BCI system. All subjects successfully completed the tasks using non-hair SSVEPs with 84.08 +/- 15.60% averaged accuracy and 30.21 +/- 10.61 bits/min averaged ITR. The empirical results of this study demonstrated the practicality of implementing an SSVEP based BCI based on signals from non-hair-bearing areas, significantly improving the feasibility and practicality of real-world BCIs. PMID- 27254872 TI - Two-Photon Imaging of DiO-Labelled Meissner Corpuscle in Living Mouse's Fingertip. AB - Meissner corpuscles are the fast adapting type I (FA-I) mechanoreceptor that locates at the dermal papillae of skin. The Meissner corpuscle is well known for its complex structure, consisting of spiral axons, lamellar cells, and a collagen capsule. Fluorescent microscopy has become a convenient method for observing the Meissner corpuscle and its inner structure. This method requires preparing samples with fingertip cross-sections and performing antibody staining before observation. Various kinds of microscopy can be used for observation, such as confocal microscopy, transmission electron microscopy (TEM), or scanning electron microscopy (SEM). Although the anatomical shape, distribution, and components of Meissner corpuscle are recognized, they have been mostly determined from observations of fixed tissues. Therefore, knowledge of mechanical transduction is limited by the lack of in vivo experiments and individual differences among samples. In this study, we propose a novel less invasive imaging method that incorporates a staining technique with lipophilic carbocyanine [Formula: see text] and two-photon microscopy. This combination allows us to repetitively observe the Meissner corpuscle in a living mouse. PMID- 27254873 TI - Visual Recognition by Learning From Web Data via Weakly Supervised Domain Generalization. AB - In this paper, a weakly supervised domain generalization (WSDG) method is proposed for real-world visual recognition tasks, in which we train classifiers by using Web data (e.g., Web images and Web videos) with noisy labels. In particular, two challenging problems need to be solved when learning robust classifiers, in which the first issue is to cope with the label noise of training Web data from the source domain, while the second issue is to enhance the generalization capability of learned classifiers to an arbitrary target domain. In order to handle the first problem, the training samples within each category are partitioned into clusters, where we use one bag to denote each cluster and instances to denote the samples in each cluster. Then, we identify a proportion of good training samples in each bag and train robust classifiers by using the good training samples, which leads to a multi-instance learning (MIL) problem. In order to handle the second problem, we assume that the training samples possibly form a set of hidden domains, with each hidden domain associated with a distinctive data distribution. Then, for each category and each hidden latent domain, we propose to learn one classifier by extending our MIL formulation, which leads to our WSDG approach. In the testing stage, our approach can obtain better generalization capability by effectively integrating multiple classifiers from different latent domains in each category. Moreover, our WSDG approach is further extended to utilize additional textual descriptions associated with Web data as privileged information (PI), although testing data do not have such PI. Extensive experiments on three benchmark data sets indicate that our newly proposed methods are effective for real-world visual recognition tasks by learning from Web data. PMID- 27254874 TI - Automated Analysis and Quantification of Human Mobility Using a Depth Sensor. AB - Analysis and quantification of human motion to support clinicians in the decision making process is the desired outcome for many clinical-based approaches. However, generating statistical models that are free from human interpretation and yet representative is a difficult task. In this paper, we propose a framework that automatically recognizes and evaluates human mobility impairments using the Microsoft Kinect One depth sensor. The framework is composed of two parts. First, it recognizes motions, such as sit-to-stand or walking 4 m, using abstract feature representation techniques and machine learning. Second, evaluation of the motion sequence in the temporal domain by comparing the test participant with a statistical mobility model, generated from tracking movements of healthy people. To complement the framework, we propose an automatic method to enable a fairer, unbiased approach to label motion capture data. Finally, we demonstrate the ability of the framework to recognize and provide clinically relevant feedback to highlight mobility concerns, hence providing a route toward stratified rehabilitation pathways and clinician-led interventions. PMID- 27254875 TI - Discovery and Clinical Decision Support for Personalized Healthcare. AB - With the advent of electronic health records, more data are continuously collected for individual patients, and more data are available for review from past patients. Despite this, it has not yet been possible to successfully use this data to systematically build clinical decision support systems that can produce personalized clinical recommendations to assist clinicians in providing individualized healthcare. In this paper, we present a novel approach, discovery engine (DE), that discovers which patient characteristics are most relevant for predicting the correct diagnosis and/or recommending the best treatment regimen for each patient. We demonstrate the performance of DE in two clinical settings: diagnosis of breast cancer as well as a personalized recommendation for a specific chemotherapy regimen for breast cancer patients. For each distinct clinical recommendation, different patient features are relevant; DE can discover these different relevant features and use them to recommend personalized clinical decisions. The DE approach achieves a 16.6% improvement over existing state-of the-art recommendation algorithms regarding kappa coefficients for recommending the personalized chemotherapy regimens. For diagnostic predictions, the DE approach achieves a 2.18% and 4.20% improvement over existing state-of-the-art prediction algorithms regarding prediction error rate and false positive rate, respectively. We also demonstrate that the performance of our approach is robust against missing information and that the relevant features discovered by DE are confirmed by clinical references. PMID- 27254876 TI - Distribution-Based Cluster Structure Selection. AB - The objective of cluster structure ensemble is to find a unified cluster structure from multiple cluster structures obtained from different datasets. Unfortunately, not all the cluster structures contribute to the unified cluster structure. This paper investigates the problem of how to select the suitable cluster structures in the ensemble which will be summarized to a more representative cluster structure. Specifically, the cluster structure is first represented by a mixture of Gaussian distributions, the parameters of which are estimated using the expectation-maximization algorithm. Then, several distribution-based distance functions are designed to evaluate the similarity between two cluster structures. Based on the similarity comparison results, we propose a new approach, which is referred to as the distribution-based cluster structure ensemble (DCSE) framework, to find the most representative unified cluster structure. We then design a new technique, the distribution-based cluster structure selection strategy (DCSSS), to select a subset of cluster structures. Finally, we propose using a distribution-based normalized hypergraph cut algorithm to generate the final result. In our experiments, a nonparametric test is adopted to evaluate the difference between DCSE and its competitors. We adopt 20 real-world datasets obtained from the University of California, Irvine and knowledge extraction based on evolutionary learning repositories, and a number of cancer gene expression profiles to evaluate the performance of the proposed methods. The experimental results show that: 1) DCSE works well on the real-world datasets and 2) DCSE based on DCSSS can further improve the performance of the algorithm. PMID- 27254877 TI - Deriving and Analyzing Analytical Structures of a Class of Typical Interval Type 2 TS Fuzzy Controllers. AB - A conventional controller's explicit input-output mathematical relationship, also known as its analytical structure, is always available for analysis and design of a control system. In contrast, virtually all type-2 (T2) fuzzy controllers are treated as black-box controllers in the literature in that their analytical structures are unknown, which inhibits precise and comprehensive understanding and analysis. In this regard, a long-standing fundamental issue remains unresolved: how a T2 fuzzy set's footprint of uncertainty, a key element differentiating a T2 controller from a type-1 (T1) controller, affects a controller's analytical structure. In this paper, we describe an innovative technique for deriving analytical structures of a class of typical interval T2 (IT2) TS fuzzy controllers. This technique makes it possible to analyze the analytical structures of the controllers to reveal the role of footprints of uncertainty in shaping the structures. Specifically, we have mathematically proven that under certain conditions, the larger the footprints, the more the IT2 controllers resemble linear or piecewise linear controllers. When the footprints are at their maximum, the IT2 controllers actually become linear or piecewise linear controllers. That is to say the smaller the footprints, the more nonlinear the controllers. The most nonlinear IT2 controllers are attained at zero footprints, at which point they become T1 controllers. This finding implies that sometimes if strong nonlinearity is most important and desired, one should consider using a smaller footprint or even just a T1 fuzzy controller. This paper exemplifies the importance and value of the analytical structure approach for comprehensive analysis of T2 fuzzy controllers. PMID- 27254878 TI - Group-Based Alternating Direction Method of Multipliers for Distributed Linear Classification. AB - The alternating direction method of multipliers (ADMM) algorithm has been widely employed for distributed machine learning tasks. However, it suffers from several limitations, e.g., a relative low convergence speed, and an expensive time cost. To this end, in this paper, a novel method, namely the group-based ADMM (GADMM), is proposed for distributed linear classification. In particular, to accelerate the convergence speed and improve global consensus, a group layer is first utilized in GADMM to divide all the slave nodes into several groups. Then, all the local variables (from the slave nodes) are gathered in the group layer to generate different group variables. Finally, by using a weighted average method, the group variables are coordinated to update the global variable (from the master node) until the solution of the global problem is reached. According to the theoretical analysis, we found that: 1) GADMM can mathematically converge at the rate , where is the number of outer iterations and 2) by using the grouping methods, GADMM can improve the convergence speed compared with the distributed ADMM framework without grouping methods. Moreover, we systematically evaluate GADMM on four publicly available LIBSVM datasets. Compared with disADMM and stochastic dual coordinate ascent with alternating direction method of multipliers-ADMM, for distributed classification, GADMM is able to reduce the number of outer iterations, which leads to faster convergence speed and better global consensus. In particular, the statistical significance test has been experimentally conducted and the results validate that GADMM can significantly save up to 30% of the total time cost (with less than 0.6% accuracy loss) compared with disADMM on large-scale datasets, e.g., webspam and epsilon. PMID- 27254879 TI - [Melanoma and Non-Melanoma Skin Cancers]. PMID- 27254880 TI - [Update on Evidence-Based Review for the Management of Cutaneous Melanoma]. PMID- 27254881 TI - [Squamous Cell Carcinoma and Basal Cell Carcinoma--The Frontline for Pathophysiology. Diagnosis and Therapy]. PMID- 27254882 TI - [Cutaneous Lymphoma--Update on the Pathophysiology, Diagnosis and Treatment]. PMID- 27254883 TI - THE RESEARCH IMPERATIVE AND THE IOM FUTURE OF NURSING: STRENGTHENING NURSING'S CONTRIBUTIONS TO LEADING CHANGE AND ADVANCING HEALTH. PMID- 27254884 TI - QUALITY AND SAFETY COMPETENCIES IN NURSING EDUCATION: STATE OF THE SCIENCE. PMID- 27254886 TI - RESEARCH METHODS FOR COMPLEXITY: FROM THE TRADITIONAL TO THE UNIQUE. PMID- 27254885 TI - AN INTEGRATIVE REVIEW OF RESEARCH ON NURSING HANDOFFS IN ACUTE CARE SETTINGS. PMID- 27254887 TI - THE "SO WHAT" FACTOR IN A TIME OF HEALTHCARE REFORM: CONDUCTING RESEARCH & EBP PROJECTS THAT IMPACT HEALTHCARE QUALITY, COST AND PATIENT OUTCOMES. PMID- 27254888 TI - TRANSLATION TEAM APPROACH: PSYCHOMETRICS OF A VIETNAMESE PAP TESTING SURVEY. PMID- 27254889 TI - Risk vs benefits of paracetamol. PMID- 27254890 TI - Optimising the management of bipolar disorder. AB - NICE recommends that when adults present in primary care with depression, they should be asked about previous periods of overactivity or disinhibited behaviour. If this behaviour lasted for four or more days referral for a specialist mental health assessment should be considered. Although depressive episodes are not necessary for a diagnosis of bipolar disorder, they are common and dominate the lifetime pattern of the condition: 50% of the time is spent in a euthymic (well) state, 38% in a depressed and 12% in a manic state. If there have only been depressive symptoms, it is not possible to exclude bipolar disorder. A diagnosis of bipolar disorder is supported by diagnostic criteria and usually confirmed by a psychiatrist. If the GP suspects mania or severe depression, or if patients are a danger to themselves or others, an urgent referral should be made for a specialist mental health assessment. If a manic episode has been present during the history the diagnosis is bipolar I disorder, while a hypomanic episode is indicative of bipolar disorder. The patient's care plan should include current health status, social situation, social support, co-ordination arrangements with secondary care, details of early warning signs, and the patient's preferred course of action in the event of a clinical relapse. Physical health checks should focus on cardiovascular disease, diabetes, obesity and respiratory disease given the heightened risk for these illnesses in bipolar disorder. PMID- 27254891 TI - Depression in young people often goes undetected. AB - Major (unipolar) depression is one of the most common mental health disorders in children and adolescents, with an estimated one year prevalence of 4-5% in mid late adolescence. Depression is probably the single most important risk factor for teenage suicide, the second to third leading cause of death in this age group and a forerunner of adult depressive disorder. Half of those with lifelong recurrent depression started to develop their symptoms before the age of 15 years. Family history is a well established risk factor and children born to depressed parents face three to four times increased rates of depression. Both genetic and environmental factors contribute to this risk. Adolescent girls are more vulnerable to depression in a ratio of 2:1. However, prepubertal depression has an equal sex ratio and is thought to be more strongly related to family dysfunction. Low mood is the predominant feature and depressed children might also have various unexplained physical symptoms, eating disorders, school refusal or substance misuse. Two thirds of adolescents with depression are thought to have at least one comorbid psychiatric disorder, most commonly the range of anxiety disorders, disruptive behavioural disorders and substance misuse problems. NICE highlights the importance of active listening and conversational techniques in order to screen for mood disorders effectively. The key questions used for screening are from the PHQ-2. PMID- 27254892 TI - Improving outcomes in diabetes in pregnancy. AB - One in 250 pregnancies in the UK involves diabetes. The majority of cases (87.5%) are gestational diabetes, 7.5% are type 1 and 5% are type 2 diabetes. Diabetes in pregnancy is associated with a five fold increase in risk of stillbirth and a two fold increased risk of congenital defects compared with the general maternity population. Fasting blood glucose levels above 5.3 mmol/L can directly affect organogenesis, particularly of the fetal heart and spine. Hyperglycaemia can cause placental failure and stillbirth and for this reason early delivery is recommended. For women with pre-existing diabetes good blood glucose control prior to conception can minimise pregnancy risks towards levels approaching that of women without diabetes. The recommended glycated haemoglobin (HbA(1c)) target in preparation for pregnancy is 48 mmol/mol (6.5%) if this can be safely achieved. Women with an HbA(1c) 86 mmol/mol should be strongly advised against pregnancy. In normal pregnancy, the increased insulin resistance mediated by placental hormone secretion is compensated by increased maternal insulin secretion to maintain euglycaemia. Gestational diabetes arises from an inability to meet these increased insulin requirements adequately. Lifestyle modification with input from a specialist diabetes dietician is key to the management of gestational diabetes. Women with gestational diabetes have a significant lifetime risk of developing type 2 diabetes, hence diabetes screening must be undertaken on an annual basis in primary care. PMID- 27254893 TI - CEREBROSPINAL MENINGITIS. 1915. PMID- 27254894 TI - Conditions in infants. PMID- 27254895 TI - Plan for the unpredictable. PMID- 27254896 TI - Home dialysis gets the spotlight--will it help? PMID- 27254897 TI - Medicaid changes coming in 2016. PMID- 27254898 TI - Patterns, causes, and effects of hyperkalemia. PMID- 27254899 TI - Potassium homeostasis in chronic kidney disease. AB - Adaptive increases in renal and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with CKD as long as the GFR remains > 15-20 mL/min. Once the GFR falls below these values, the impact of factors known to adversely affect K+ homeostasis is significantly magnified. Impaired renal K+ excretion can be the result of conditions that severely limit distal Na+ delivery, decreased mineralocorticoid levels or activity, or a distal tubular defect (Table 2). In clinical practice, hyperkalemia is usually the result of a combination of factors superimposed on renal dysfunction. PMID- 27254900 TI - Clinical and electrophysiological consequences of hyperkalemia. PMID- 27254901 TI - Heart failure with reduced ejection fraction. Hyperkalemia and worsening renal function as challenges to implementation (guidelines vs real-world). PMID- 27254902 TI - Arrhythmias and sudden cardiac death in hemodialysis patients. Temporal profile, electrolyte abnormalities, and potential targeted therapies. PMID- 27254903 TI - Current and future potassium binders. PMID- 27254904 TI - In search of a dialysis unit. An innovative approach in addressing patient placement challenges. PMID- 27254905 TI - NKF program offers nutritional fundamentals and complex challenges for the RD. PMID- 27254906 TI - NFK 2016 Spring Clinical Meetings. Social work program stresses interventions. PMID- 27254907 TI - DaVita seeing success with STI approach. PMID- 27254908 TI - How to improve living donation. PMID- 27254909 TI - [Effects of Chemical Fertilizers and Organic Fertilizer on Yield of Ligusticum chuanxiong Rhizome]. AB - OBJECTIVE: To study the effects of different N, P, K and organic fertilizer (OF) on yield of Ligusticum chuanxiong rhizome, in order to provide the theoretical foundation for the establishment of standardization cultivation techniques. METHODS: The field plot experiments used Ligusticum chuanxiong rhizome which planted in Pengshan as material, and were studied by the four factors and five levels with quadratic regression rotation-orthogonal combination design. According to the data obtained, a function model which could predict the fertilization and yield of Ligusticum chuanxiong rhizome accurately was established. RESULTS: The model analysis showed that the yields of Ligusticum chuanxiong rhizome were significantly influenced by the N, P, K and OF applications. Among these factors, the order of increase rates by the fertilizers was K > OF > N > P; The effect of interaction between N and K, N and OF, K and OF on the yield of Ligusticum chuanxiong rhizome were significantly different. High levels of N and P, N and organic fertilizer, K and organic fertilizer were conducive to improve the yield of Ligusticum chuanxiong rhizome. The results showed that the optimal fertilizer application rates of N was 148.20 - 172.28 kg/hm2, P was 511.92 - 599.40 kg/hm2, K was 249.70 - 282.37 kg/hm2, and OF was 940.00 - 1 104.00 kg/hm2. CONCLUSION: N, P, K and OF obviously affect the yield of Ligusticum chuanxiong rhizome. K and OF can significantly increase the yield of Ligusticum chuanxiong rhizome. Thus it is suggested that properly high mount of K and OF and appropriate increasing N are two favorable factors for cultivating Ligusticum chuanxiong. PMID- 27254910 TI - [Phenotypic Trait Variation, Correlation and Path Analysis of Clerodendranthus spicatus]. AB - OBJECTIVE: To investigate the phenotypic trait variation range of Clerodendranthus spicatus, and to look for phenotypic traits closely related with its yield and quality, in order to provide reference for its breeding. METHODS: Randomly labelled plants of Clerodendranthus spicatus, observed its phenotypic traits and analyzed by variation, principal component, correlation and path analysis. RESULTS: 13 phenotypic traits in the 15 germplasms of Clerodendranthus spicatus had great variations, the variations mainly distributed in yield, growth and genetic characteristics. Correlation and path analysis showed that, the plant dry weight had an extremely significantly positive correlation with fresh weight, and a positive correlation with stem height, stem diameter and root diameter. Plant fresh weight had a majorly direct contribution to the plant dry weight, stem height, stem diameter and root diameter also had a direct contribution to the plant dry weight. The other characters, including root length, branches, the number of leaf nodes, leaf number, leaf length, leaf width, fresh weight/dry weight ratio, rosmarinic acid content and ursolic acid content all had a negatively direct contribution to the plant dry weight. Rosmarinic acid content had a positive correlation with fresh weight, and a significantly positive correlation with fresh weight/dry weight ratio. Fresh weight had a majorly direct contribution to the rosmarinic acid content, stem height and stem diameter also had a direct contribution to the plant rosmarinic acid content. The other characters, including root length, root diameter, branches, the number of leaf nodes, leaf length, leaf width, dry weight, fresh weight/dry weight ratio, and ursolic acid content all had a negatively direct contribution to the rosmarinic acid content. CONCLUSION: The phenotypic traits of Clerodendranthus spicatus had rich variations on yield, growth and genetic characteristics. When choosing good germplasm, plant fresh weight, stem height, stem diameter and plant fresh weight/dry weight ratio having promoting effects on the plant dry weight and rosmarinic acid content should be considered comprehensively, and plant with vigorous growth, tall stem and more leaves can be choosed firstly. PMID- 27254911 TI - [Comparative Study on Photosynthetic Characteristics and Medicinal Ingredients in Different Months of Inula nervosa]. AB - OBJECTIVE: To compare the photosynthetic characteristics and medicinal ingredients in different months in order to provide a theoretical basis for cultivation and harvest of Inula nervosa. METHODS: The photosynthetic characteristics was measured by using LI-6400 and morphological characteristics were compared in different months, and the contents of total flavonoids and total phenols were determined by UV spectrophotometry. RESULTS: Net photosynthetic rate of Inula nervosa was the highest in June, which showed a single peak curve, and the average of daily change reached to 8.50 MUmol/(m2 x s). Light response curve data showed the ability of using the strongest light was in June. Chlorophyll fluorescence parameters values also displayed that, openness of reflect center and photochemical efficiency of leaves' photosystem II were the highest, which also had the fastest rate of electron transfer in June. Morphological indicators showed that the single leaf area and leaf area of Inula nervosa were significantly higher in June than those in other months. The content of total phenols were much higher than that of total flavonoids in Inula nervosa. And the medicinal ingredient content of the underground part was higher than that in the aerial part. CONCLUSION: The best harvest time of underground part of Inula nervosa should be after autumn, when the weight and active ingredients are accumulated to a considerable level. PMID- 27254912 TI - [Highly Frequent Regeneration System Establishment of Lycium ruthenicum]. AB - OBJECTIVE: To establish a rapid regeneration system of Lycium ruthenicum in order to produce large-scale commodity seedlings. METHODS: Cotyledon, hypocotyl and radicle of Lycium ruthenicum seedlings were used as explants to produce plantlets by depending on MS basal medium mixed with the different kinds and different concentration of hormones. RESULTS: The desirable hormone composition for the inducement was MS + 6-BA 1.0 mg/L + NAA 0.5 mg/L, and the callus induction rate was as high as 100%, the optimum medium for the buds sprouting and regeneration was that of MS + 6-BA 0.5 mg/L + NAA 0.5 mg/L, with a propagation coefficient of 7.73, and the suitable medium for the roots induction was 1/2MS + IBA 1.0 mg/L, 90% of the regenerated plantlets transferred to an open field survive and grow well. CONCLUSION: The callus can be induced by cotyledon, hypocotyls and radicle of Lycium ruthenicum seedlings, and hypocotyls is the best explants for callus induced. The formulations suitable for callus induction, differentiation, bud proliferation and rooting are screened out to establish the rapid regeneration system for Lycium ruthenicum. PMID- 27254913 TI - [Chemical Constituents from Periplaneta americana]. AB - OBJECTIVE: To study the chemical constituents in Periplaneta americana. METHODS: The chemical constituents were separated and purified by chromatographic methods after solvent extraction and identified by spectroscopic analyses. RESULTS: Ten compounds were isolated from Periplaneta americana and identified as following: 8 hydroxy-3,4-dihydroquinolin-2 (1H)-one (1), cyclo-( L-Phe-L-Pro) (2), cyclo-(Pro Ile) (3), cyclo-(L-Pro-D-Leu) (4), brevianamide F (5), cyclo-(Ile-Ala) (6), cyclo ( L-Val-L-Pro) (7), cyclo-(L-Pro-L-Tyr) (8), cyclo-(Trp-Val)-dipeptide (9), and ( )-(1S, 3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (10). CONCLUSION: Compounds 2 - 9 are isolated from Periplaneta americana for the first time. PMID- 27254914 TI - [Species, Damage and Community Structure of Weeds in Scrophularia ningpoensis Fields in Nanchuan, Chongqing]. AB - OBJECTIVE: To investigate the damage and community structure of weeds in Scrophularia ningpoensis fields in Nanchuan, Chongqing. METHODS: From 2013 to 2014, an investigation was carried out by inverted W-9 point sampling method to study the weed species. RESULTS: 96 weed species belonged to 75 genera of 30 families were observed, including 18 species of Asteraceae weeds (accounted for 18.75%), 10 species of Poaceae weeds (accounted for 10.42%). Moreover, there were 57 species of annual weeds (accounted for 59.38%) and 39 species of perennial weeds (accounted for 40.63%). The overall abundance of Erigeron annuus, Digitaria adscendens, Torilis scabra, Polygonum nepalense, Ranunculus japonicas, Stellaria media and Commelina communis were relatively higher than that of the others. CONCLUSION: The difference of weed species and community structure might result from the physical and chemical characteristics of soil, moisture content, cropping system, tillage type, environmental and climatic conditions, crop distribution and weed control. PMID- 27254915 TI - [Effects of Crude Atractylodis Rhizoma and Processed Atractylodis Rhizoma on AQP1 - AQP5 and Hemorheology in Healthy Rats]. AB - OBJECTIVE: To study the different effects of crude Atractylodis Rhizoma and processed Atractylodis Rhizoma in healthy rats, in order to prove the traditional theory that the crude Atractylodis Rhizoma has dry effects and the dry effects can be weaken by processing. METHODS: Health rats had been orally administered with pure water, crude Atractylodis Rhizoma, processed Atractylodis Rhizoma and atropine. The concentration of AQP1 and AQP5 in submaxillary gland were measured by ELISA. Their index of submaxillary gland, hemorheology and moisture content of intestine were also measured. RESULTS: There were obvious differences of concentration of AQP1 and AQP5 in submaxillary gland, index of submaxillary gland, hemorheology and moisture content of intestine between the rats which had been orally administered crude Atractylodis Rhizoma and the rats administered processed Rhizoma Atractylodes. CONCLUSIONS: The dry effects of Atractylodis Rhizoma works on rats' moisture content of intestine, index of submaxillary gland and hemorheology. The dry effects can be weaken by processing. PMID- 27254916 TI - [UPLC Fingerprints of Euphorbiae Ebracteolatae Radix and Its Vinegar-Processed Slices]. AB - OBJECTIVE: To compare the qualities of Euphorbiae Ebracteolatae Radix from different original plants and its vinegar-processed slices. METHODS: UPLC fingerprints of Euphoria ebracteolata, Euphoria fischeriana and vinegar-processed slices of Euphoria ebracteolata were established on a Waters ODS column (100 mm x 2.1 mm, 1.8 MUm), using jolkinolide B as the reference substance. A mixture of acetonitrile and water was used as the mobile phase in a gradient elution mode, with the flow rate of 0.4 mL/min, the column temperature at 30 degrees C and the UV detector at 210 nm. The UPLC analysis time was no more than 20 min. RESULTS: The qualities of Euphoria ebracteolata and its vinegar-processed slices were stable with similarities over 0.90, respectively. However, the fingerprints of the slices and their original crude drugs exhibited obvious difference on both number and the relative peak area of the common peaks. Meanwhile the similarities of the fingerprints of Euphoria fischeriana and Euphoria ebracteolata were less than 0.72, indicating significant difference of these two plants. CONCLUSION: The developed method is available for quality control of Euphorbiae Ebracteolatae Radix and mechanism exploration of its vinegar-processed slices. PMID- 27254917 TI - [Application of Cocktail Probe Drugs for Detecting Influences of Raw and Processed Phellodendri Cortex on Cytochrome P450 Isoforms]. AB - OBJECTIVE: To research and compare the influences of raw and processed Phellodendri Cortex on the cytochrome P450 four isoforms by Cocktail probe drugs, and to explore the processing principle of Phellodendri Cortex. METHODS: SD rats were randomly divided into raw group,processed with rice-wine group, processed with salt-water group and blank control group, which were given raw decoction, processed with rice-wine decoction, processed with salt-water decoction (3.24 g/kg) and normal saline respectively for one week, then given the mixture of four probe drugs on the 8th day, and soon after the blood samples were obtained through the orbits at a series of time-points. HPLC method was used to determine the concentrations of probe drugs in rat plasma, and pharmacokinetic parameters were estimated by DAS3.0. The effect of raw and processed Phellodendri Cortex on cytochrome P450 were judged indirectly by the pharmacokinetic parameters. RESULTS: Compared with the blank control group, the t1/2 significantly increased of theophylline in raw and processed with salt-water group. The CL/F significantly decreased and AUC(0-t) AUC(0-infinity). significantly increased of theophylline in raw and processed with rice-wine groups. The t(1/2) AUC(0 infinity) and AUC(0-infinity) significantly decreased and CL/F significantly increased of dapsone in raw, processed with rice-wine and processed with salt water group. The AUC(0-t) significantly increased of chlorzoxazone in raw and processed with salt-water group. The t(1/2), AUC(0-infinity). and AUC(0-t) significantly decreased and CL/F significantly increased of chlorzoxazone in processed with rice-wine group. The AUC(0-t), significantly decreased of tolbutamide in raw, processed with rice-wine and processed with salt-water groups. CONCLUSION: The raw Phellodendri Cortex can inhibit CYP1A2, induce CYP3 A4 and also is need to make a further research work on CYP2C9 and CYP2E1. Meanwhile, it also can change the activities of cytochrome P450 after processed with rice-wine and salt-water. The Phellodendri Cortex processed with rice-wine can reduce the inhibitory effect of CYP1A2 and enhance induction of CYP3A4, it provides reference and basis to make an interpretation about Phellodendri Cortex processed with rice-wine. PMID- 27254918 TI - [GPC Fingerprint Chromatograms of Aloe vera Leaf Gel Polysaccharides]. AB - OBJECTIVE: To establish the gel permeation chromatography (GPC) fingerprint chromatograms of polysaccharides in Aloe vera leaf gel from the same habitat (Beijing) and different habitats for evaluating the quality of Aloe vera leaf gel products commercially available and testing common adulterated substances. METHODS: The samples were prepared by water-extraction and alcohol-precipitation method. GPC separation was performed on a Shodex SUGAR KS-805 (300 mm x 8.0 mm, 7 MUm) column and a Shodex SUGAR KS-803 (300 mm x 8.0 mm, 6 MUm) column at the temperature of 60 degrees C by eluting with 0.1 mol/L NaNO3 (containing 0.2 per thousand NaN) at a flow rate of 0.8 mL/min, the chromatographic effluent was detected by refractive index detector (RID) at the temperature of 50 degrees C. RESULTS: The common pattern of GPC fingerprint chromatograms was established and four common peaks were demarcated. The similarities of samples from the same habitat (Beijing) and different habitats were over 0.9. Taking the GPC fingerprint chromatograms for the qualified model, three commercially available aloe products were evaluated to be made of Aloe vera by the different manufacturing processes and four common adulterated substances of aloe polysaccharides were identified effectively. CONCLUSION: The method is simple and accurate with a good reproducibility, and it can be used for the identification and quality evaluation of Aloe vera leaf gel products. PMID- 27254919 TI - [Antitumor Chemical Entities of Cordyceps taii Mycelia Powder from Guizhou]. AB - OBJECTIVE: To seperate and identify the chemicals from the antitumor fraction of Cordyceps taii mycelia powder. METHODS: The mycelia of Cordyceps taii were prepared by the submerged fermentation technique. Chemical entities in the antitumor fraction of Cordyceps taii were isolated and purified by using different column chromatographies (silica gel, Sephadex LH-20 and MCI), and semi preparative HPLC method. Theirs chemical structures were then identified by different spectrum techniques such as EI, ESI and 1D/2D-NMR, etc. The cytotoxic activity was investigated by the Sulforhodamine B (SRB) assay. RESULTS: Six compounds, such as 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (1), ergosterol (2), adenine nucleoside (3), helvolic acid (4), deacetylcytochalasin C (5) and zygosporin D (6), were identified. The IC50 value of compound 2 against human gastric cancer cell line SGC-7901 was 5.99 MUmol/L, which was less than the half value of cisplatin, and had lower cytotoxicity to normal cells in comparison with cisplatin. CONCLUSION: Six compounds have been isolated from the antitumor fraction of Cordyceps taii mycelia powder,of which compounds 1, 5 and 6 are isolated from Cordyceps taii for the first time. Compounds 1, 2 and 4 have cytotoxic activities against cancer cells, and should be the main antitumor compounds of Cordyceps taii. PMID- 27254920 TI - [Sesquiterpenes of Chloranthus serratus Root]. AB - OBJECTIVE: To study sesquiterpenes from the root of Chloranthus serratus. METHODS: The sesquiterpenes of Chloranthus serratus were isolated and purified by various chromatographic techniques, such as silica gel, Sephadex LH-20 and preparative HPLC. The structures of these isolated compounds were identified by spectroscopic analysis. RESULTS: Ten sesquiterpenes were isolated and identified as follows: 1beta, 8beta-dihydroxy-eudesman-4 (15), 7 (11) -dien-8alpha, 12-olide (I), curcolonol (II), 4beta, 8beta-dihydroxy-5alpha (H) -eudesm-7 (11) -en-8, 12 olide (III), 1beta, 8,beta-dihydroxy-eudesman-3, 7 (11) -dien-8alpha, 12-olide (IV), multistalactone E (V), zedoarofuran (VI), 8beta,9alpha-dihydroxylindan 4(5), 7(11) -dien-8alpha,12-olide(VII), serralactone A (VIII), 8-epi-ivangustin (IX), and chloranthalactone E (X ). CONCLUSION: Compounds I, II, IV - VII, IX and X are isolated from Chloranthus serratus for the first time. PMID- 27254921 TI - [Chemical Constituents of Citrus medica Fruit]. AB - OBJECTIVE: To study the chemical constituents of Citrus medica fruit. METHODS: The fruit of Citrus medica was extracted with 95% EtOH, and the compounds were separated and purified by silica gel, RP-18 and Sephadex LH-20 column chromatography. The structures were identified by spectroscopic analysis. RESULTS: A total of 16 compounds were isolated and identified, including methyl ferulic acid (1), dihydro-N-caffeoyltyramine (2) acacetin (3), beta-ecdysterone (4), (-)-balanophonin (5), p-methoxy cinnamic acid (6), umbelliferone (7), ferulic acid (8), pyrocatechualdehyde (9), diosmetin (10), 4-methoxy salicylic acid (1), beta-amyrin acetate (12), epigallocatechin (13), betulinic acid (14), lupeol (15) and nicotinamide (16). CONCLUSION: All the compounds are isolated from the fruit of Citrus medica for the first time. PMID- 27254923 TI - [Chemical Compositions from Stems and Branches of Sorbaria arborea]. AB - OBJECTIVE: To investigate the chemical constituents from the stems and branches of Sorbaria arborea. METHODS: The chemical constituents were isolated and purified by silica gel column chromatography, Sephadex LH-20 column chromatography and recrystallization. Their structures were identified by physicochemical properties and spectra analysis. RESULTS: Ten compounds were isolated and identified as ursolic acid (1), cucurbitacin F (2), (-) -epicatechin (3), daucosterol (4), arbutin (5), 3-O-beta-anthemisol (6), 2,6-dimethoxy-p hydroquinone-4-O-beta-D-glucopyranoside (7), lupeol (8), betulin (9) and lup-20 (29) -en-3beta, 30-diol (10). CONCLUSION: All the compounds are isolated from this plant for the first time, and compounds 1, 6 - 8 and 10 are obtained from Sorbaria genus for the first time. PMID- 27254922 TI - [Chemical Constituents from Drypetes hainanensis Stems and Leaves]. AB - OBJECTIVE: To study the chemical constituents from the stems and leaves in Drypetes hainanensis. METHODS: The constituents were isolated and purified by various chromatography, and the structures were identified by extensive spectral analysis. RESULTS: Eleven compounds were isolated and identified as syringaresinol-4-O-glycoside (1), koaburaside (2), abietin (3) syringin (4), kelampayoside A (5), 7,7'-bis-(4-hydroxy-3,5-dimethoxyphenyl)-8,8' dihydroxymethyl-tetrahydrofuran-4-O-beta-glucopyranoside (6), amentoflavone (7), 3,4,5-trimethoxyphenyl-beta-D-glucopyranoside (8),1,4-di-O-methyl-myo-inositol (9), glycerol (10) and succinic acid (11). CONCLUSION: All the compounds are isolated from this plant for the first time. PMID- 27254924 TI - [Chemical Constituents from Camellia oleifera Stem]. AB - OBJECTIVE: To study the chemical constituents of stem of Camellia oleifera. METHODS: The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. RESULTS: Seven compounds were isolated from the stem of Camellia oleifera, whose structures were elucidated as (-) -pinoresinol (1), (-) -medioresinol (2), skullcapflavone II (3), betulinic acid (4), ursolic acid (5), 3-O-beta-D glucopyranosyl- (1 --> 2) -beta-D-xylopyransoyl-(1 --> 3) -[beta-D-glucopyranosyl (1 --> 2)] -beta-D-glucuronopyranosyl-22alpha-angeloyloxyolean-12-ene 15alpha,16alpha,28-triol (6) and oleanolic acid (7). CONCLUSION: Compounds 1 - 6 are isolated from this plant for the first time, and compounds 1 - 3 are isolated from this genus for the first time. PMID- 27254925 TI - [Comparative Analysis of Content of Four Alkaloids in Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea]. AB - OBJECTIVE: To establish an assay method for simultaneous determination of peimine, peiminine, peimissine and hupehenine and to make a comparative analysis of the content of four alkaloids in Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea for the first time. METHODS: A Unitary C18 column(250 mm x 4.6 mm, 5 MUm) was chosen with acetonitrile-water (containing 0.05% diethylamine) as mobile phase in a gradient program. The column temperature was 35 degrees C and the flow-rate was 1.0 mL/min. RESULTS: There was high content of peiminine and the content of peimissine was inferior to peiminine in Fritillaria hupehensis. Relatively speaking, peimine and hupehenine were much lower than the other two ingredients. Fritillaria ebeiensis var. purpurea also contained high levels of peiminine, the minimum content of peimine and equivalent content of peimissine comparing with Fritillaria hupehensis. In addition, it didn't contain hupehenine in Fritillaria ebeiensis var. purpurea. CONCLUSION: This method is simple and fast, and it has good separation, reproducibility and reliable results. Also, it can be used as basis for the quality evaluation of Fritillaria hupehensis and Fritillaria ebeiensis var. purpurea. PMID- 27254926 TI - [Polyketone Reaction in Biosynthetic Pathways of 2, 3, 5, 4'-Tetrahydroxy Stilhene-2-O-beta-D-glucoside in Polygonum multiflorum by Biocatalysis]. AB - OBJECTIVE: 2, 3, 5, 4'-Tetrahydroxy stilbene-2-O-beta-D-glucoside (THSG), the active ingredient of Polygonum multiflorum, its polyketone reaction in the biosynthesis pathways was studied by biocatalysis method. METHODS: The substrates 4-coumaroyl-CoA and malonyl-CoA were catalyzed in vitro by the crude enzyme extracted from Polygonum multiflorum callus, then the products were verified by HPLC and LC-MS methods. And the crude enzyme was analyzed by ammonium sulfate precipitation method and SDS-PAGE. RESULTS: HPLC chromatogram showed the same retention time of both the product and resveratrol standards; LC-MS spectra showed that the m/z of product was 227, which was consistent with resveratrol standards under the mode of negative ion; Ammonium sulfate (AS) precipitation method showed AS of 40% - 70% had catalytic activity,and 50% - 60% was the optimum; SDS-PAGE showed protein bands were obviously different among different AS concentration between 20% - 80%, the protein band of 42 kDa was found in AS of 50% - 60%, which had the same molecular weight with stilbene synthase. CONCLUSION: The product of polyketone reaction in the biosynthesis of THSG is resveratrol rather than THSG, so it is speculated that THSG is the conversion product of resveratrol instead of the direct product of the polyketone reaction. PMID- 27254927 TI - [Effect of Danzhi Jiangtang Capsule on Myocardial Fibrosis in Diabetic Rats]. AB - OBJECTIVE: To investigate the effect of Danzhi Jiangtang Capsule on myocardial fibrosis in diabetic rats with fluctuated blood glucose and the possible mechanisms implicated. METHODS: Following induction of diabetes with intraperitoneal injection of streptozotocin (STZ), rats were administered with insulin or glucose at different time during a day to induce blood glucose fluctuation. After treatment with Danzhi Jiangtang Capsule for six weeks, rats were sacrificed and the hearts were collected for the determination of cardiac mass index. Cardiac levels of angiotensin II (Ang II), type I and type III collagens and transforming growth factor-beta1 (TGF-beta1) were assayed by ELISA. Levels of Smad3 phosphorylation and protein expression of matrix metalloproteinase-2 ( MMP-2) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) were determined by Western blot analysis. Total antioxidant capacity and malondialdehyde (MDA) content in cardiac tissues were measured colorimetrically. RESULTS: Treatment with Danzhi Jiangtang Capsule for six weeks significantly reduced cardiac mass index and cardiac levels of type I and type III collagens (P < 0.05 or P < 0.01). Levels of Ang II, TGF-beta1 and Smad3 phosphorylation in cardiac tissues were also decreased markedly (P < 0.05 or P < 0.01). Supplementation with Danzhi Jiangtang Capsule resulted in an evident up regulation of MMP-2 protein and down-regulation of TIMP-2 protein expression in cardiac tissues (P < 0.05 or P < 0.01). In addition, Danzhi Jiangtang Capsule significantly enhanced total antioxidant capacity in diabetic rats, while cardiac content of MDA was decreased markedly( P < 0.05 or P < 0.01). CONCLUSION: Danzhi Jiangtang Capsule significantly ameliorated myocardial fibrosis in diabetic rats with fluctuated blood glucose, which might be derived from enhancement of antioxidant capacity, suppression of RAS and TGF-beta1/Smad3 signaling pathway and regulation of MMP-2/TIMP-2 protein expression. PMID- 27254928 TI - [Pharmacokinetic Study on Brucine in Different Administration Methods of Liposome in Rats]. AB - OBJECTIVE: To compare the pharmacokinetic differences of brucine in rats after different administration methods of brucine liposome. METHODS: To determine brucine in rat plasma at different points in time by HPLC after oral administration, intramuscular injection, subcutaneous injection and intravenous injection of brucine liposome, respectively. The pharmacokinetic parameters were calculated and analyzed by DAS 3.0. RESULTS: Compared with other groups, AUC(0 - > t) of subcutaneous injection were higher, C(max) were lower and MRT(0 --> 1), were significantly improved. The pharmacokinetics parameters and absolute bioavailability of brucine show that bioavailability in rats after different administration methods of brucine liposome is subcutaneous injection > intramuscular injection > oral administration. PMID- 27254929 TI - [Anti-proliferation Effect of Taraxacum mongolicum Extract in HepG2 Cells and Its Mechanism]. AB - OBJECTIVE: To study the anti-proliferation effect of Taraxacum mongolicum extract in HepG2 cells and its mechanism. METHODS: The total proteins of HepG2 cells treated with Taraxacum mongolicum extract were. extracted and mitochondria mediated apoptosis-related proteins (Survivin, Mcl-1, BCL-xL, BCL-2, Smac, BAX, Bad, Cytochrome c and Caspase-3/7/9) were detected by Western blot. RESULTS: Taraxacum mongolicum extract obviously inhibited the proliferation of HepG2 cells and the expression of anti-apoptotic proteins (Survivin, BCL-xL and BCL-2), increased the expression of pro-apoptotic proteins (Smac and Caspase-3/7/9), and promoted the release of Cytochrome c from mitochondria to cytoplasm in HepG2 cells. The effects were in a dose-independent mode. CONCLUSION: Taraxacum mongolicum extract can inhibit the proliferation of HepG2 cells and the anti proliferation mechanism is related to mitochondria-mediated apoptosis. PMID- 27254930 TI - [Anti-hypertensive Effect of Total Flavonoids of Cydonia oblonga Leaves and Its Mechanism Based on Anti-inflammatory Function]. AB - OBJECTIVE: To study the anti-hypertensive effect of total flavonoids of Cydonia oblonga leaves in spontaneously hypertensive rats, then to preliminarily investigate the mechanism of action based on anti-inflammatory function. METHODS: Spontaneously hypertensive rats were divided into six groups as spontaneously hypertensive control group (SHR), captopril group (25 mg/kg), Eucommia ulmoides group (30 mg/kg), total flavonoids of Cydonia oblonga leaves low (40 mg/kg), middle (80 mg/kg) and high dose (160 mg/kg) groups. Eight Wistar-Kyoto (WKY) rats were given distilled water as the control. The drugs were given by intragastric administration for 16 weeks, then the contents of IL-1beta, IL-6, IL-10, TNF alpha and CRP in rats serum were detected. The weight and the blood pressure of rats were measured at 0 min and 2, 4, 6, 8, 10, 12, 14, 16 weeks after drug administrated. RESULTS: Compared with control group, the contents of IL-1beta, IL 6, TNF-alpha and CRP were increased and IL-10 was decreased; Compared with SHR group, the contents of IL-1beta,IL-6, TNF-alpha and CRP were decreased in total flavonoids of Cydonia oblonga leaves groups. CONCLUSION: Total flavonoids of Cydonia oblonga leaves show an anti-hypertensive activity in spontaneously hypertensive rats and the mechanism is related to the function of anti inflammatory. PMID- 27254931 TI - [Mechanism of Musk and Borneol on Inflammatory of Cerebral Ischemia and Reperfusion Injury at Different Time Points of Acute Phase in Rats]. AB - OBJECTIVE: To investigate the mechanism of Musk and Borneol on cerebral ischemia and reperfusion injury at different time points of acute phase in rats. METHODS: 180 rats were divided into seven groups including sham, ischemia-reperfusion after 24 h and 72 h model group, Musk 50 and 25 mg/kg groups, Borneol 50 and 25 mg/kg groups, and Xingnaojing 10 mL/kg group. Ischemia-reperfusion model was made after administration of each drug. The neurologic impairment scores at different time points after ischemia and reperfusion was evaluated, activities of cyclooxygenase (COX-2) and 5-lipoxygenase (5-LOX) in brain tissue were determined, and the expression of CysLT2 protein and mRNA in hippocampus were explored. RESULTS: Musk and Borneol significantly improved the neurologic impairment scores of ischemia-reperfusion injury rats, improved the pathological morphology of rats brain tissue, reduced the activities of COX-2 and 5-LOX in brain homogenates,and inhibited the expression of CysLT2 protein in hippocampus. CONCLUSION: Musk and Borneol have protective effect on inflammatory injury of acute injury in ischemia-reperfusion injury rats, the mechanism is related to inhibition the activity of COX-2 and 5-LOX in brain. PMID- 27254932 TI - [Nasal Mucosa Absorption of Scutellariae Radix Extract in Rats and Its Two Preparations Phospholipid Complex and Submicron Emulsion]. AB - OBJECTIVE: To study the nasal mucosa absorption of Scutellariae Radix extract in rats and its two preparations phospholipid complex and submicron emulsion, and to evaluate the rationality of Scutellariae Radix extract modification technology and preparation form. METHODS: According to the nasal absorption method, the absorption amount of Scutellariae Radix extract, phospholipid complex and submicron emulsion were determined. RESULTS: The absorption amount of Scutellariae Radix extract, phospholipid complex and submicron emulsion under the experimental conditions was improved in turn in 2 h and the absorption amount of submicron emulsion increased significantly. The absorption characteristics were passive diffusion. CONCLUSION: The modification methods and preparation form of Scutellariae Radix extract were scientific and reasonable. PMID- 27254933 TI - [Identification of Volatile Chemical Constituents from Hui Formula "Ha Hei Lili" by GC-MS]. AB - OBJECTIVE: The volatile components of the Hui formula "Ha Hei Lili" were extracted by steam distillation extraction (SD) and supercritical CO2 fluid extraction, and the structures were analyzed and identified by GC-MS. METHODS: The GC-MS conditions were set as follows: Rxi-5Sil MS quartz capillary column (30 m x 0.25 mm, 0.25 MUm), the initial temperature of 50 degrees C to keep 1 min, to 10 degrees C/min heating to 120 degrees C, maintained 3 min, then to 3 degrees C/min heating to 200 degrees C, maintained 3 min, and then to 5 degreesC/min heating to 290 degrees C, maintained until completion of analysis; helium as the carrier gas, column flow rate 1.0 ml/min, split ratio 25: 1, inlet temperature 250 degrees C, EI ionization source 70 eV, ion source temperature 230 degrees C, scan range of m/z 35 - 500. RESULTS: Yield of volatile oil were 0.21% and 5.44% extracted by SD and SFE methods, respectively; and for SD method, 36 kinds of compounds were identified, accounted for 87.02% of total mass of volatile oil; for SFE method, 38 kinds of constituents were identified, accounted for 97.47% of total mass of volatile oil. CONCLUSION: The type of constituents contained in the volatile oil extracted by SD and SFE methods are totally different; and GC-MS can be used to identify the structures and relative content of volatile components, the results of this study can provide an experimental basis for development and utilization of Hui formula "Ha Hei Lili". PMID- 27254934 TI - [HPLC Fingerprint of QingGuangAn and Determination of the Main Components]. AB - OBJECTIVE: To establish an HPLC fingerprint of ethanol extract of QingGuangAn, and to determine the contents of paeoniflorin and calycosin-7-glucosid. METHODS: HPLC analysis was performed on an Agilent 1260 Infinity LC system and carried out at 35 degrees C on a column of GRACE Alltima C18 (250 mm x 4.6 mm, 5 MUm). A binary gradient elution system was composed of acetonitrile (phase A) and water solution (phase B). Detection was performed at the wavelength of 254 nm, the mobile flow rate was 0.8 mL/min. A matrix including 20 variations (characteristic peaks area) and 10 samples was constructed for similarity evaluation. RESULTS: The results showed that the collected samples had a good similarity. A specificity fingerprint was produced and 20 characteristic peaks were designated. The content of paeoniflorin and calycosin-7-glucosid was 0.368 and 0.049 mg/g, respectively. CONCLUSION: It is a reliable, available and quick method for quality control of QingGuangAn,which provides some reference for the comparison of different extracting methods of QingGuangAn and the differences of pharmacodynamic. PMID- 27254935 TI - [Mechanism of COPD]. PMID- 27254936 TI - [Concept and management of COPD, from past to future]. AB - Our understanding of chronic obstructive pulmonary disease (COPD) has changed dramatically over the past two decades, especially since the first launching of GOLD document in 2001. The first GOLD workshop reports showed the global strategy for the diagnosis, management and prevention of COPD at that time. Its goal was to increase awareness of COPD, and a nihilistic attitude toward COPD occupied a dominant position due to the disappointment with available treatment options. Thereafter, both pharmacologic and non-pharmacologic treatments' options have steadily progressed, while the 'COPD' notion has moved from an airflow limitation centric view to a complex and heterogeneous disease, which leads inevitably to the need for personalizing the assessment and treatment of patients with COPD. PMID- 27254937 TI - [Outline of JRS COPD guideline Ed. 4]. AB - JRS COPD guideline Edition 4 updated current concept for clinical management of COPD in Japan. Minor but substantial changes were added to the definition and subtype of the disease. In pharmacological treatment, single use of LAMA or LABA is equally the first choice. If it is not enough, those combination are recommended. A-D classification that was presented in GOLD report 2011 was not adopted. In non-pharmacological treatment, pulmonary rehabilitation is steadily effective and essential. In terms of survival prognosis, at least, the concept of physical activity is important. Those improvement and maintenance were newly added to the objectives of the clinical management of COPD. PMID- 27254939 TI - [Etiological and exacerbation factors for COPD. Air pollution]. AB - Recently, it has been found that the number of patients with chronic obstructive pulmonary disease (COPD) who do not have a history of smoking is higher than expected, and a number of factors affect the development of COPD. Although adequate evidence for the relation of ambient air pollution, including the presence of particulate matter (PM2.5), with the development of COPD is lacking, higher mortality from respiratory and cardiovascular diseases has been reported among patients exposed to air pollution for a long time. In addition, several reports have pointed out the possibility that acute exacerbation of COPD can be caused by short-term exposure to air pollution. Tobacco smoke is the main cause of highly concentrated PM2.5 indoors, and second hand smoke is related with the development of COPD and the high mortality from COPD. In developing countries, biomass fuel combustion contributes to COPD, especially among housewives who do not smoke. PMID- 27254938 TI - [Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)]. AB - A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD. PMID- 27254940 TI - [Etiological and exacerbation factors for COPD. Respiratory tract infections]. AB - Respiratory tract infections are important events in the pathophysiology of COPD, and are known as one of the risk factors for COPD onset. More importantly, they are the most common risk factor of COPD exacerbations. As microorganisms for the causes of infections, both virus and bacteria are representative. Since exacerbations increase the decline in lung function, deterioration in health status and risk of death in COPD, prevention of exacerbations via appropriate long-term management, including smoking cessation, influenza and pneumococcal vaccinations, and pharmacotherapy, is very important. However, if exacerbations occur, early intervention with antibiotics, bronchodilators, and systemic corticosteroids administration should be considered to minimize poor outcomes. PMID- 27254941 TI - [Etiological and exacerbation factors for COPD. Body weight loss]. AB - Hunger or malnutrition is not only a historical issue but also a current problem worldwide. Biological responses to hunger are evolutionary prepared in our body, including energy generation by degradation of body proteins. Extreme weight loss (malnutrition) can cause air space enlargement in human and rodents. However, the changes in rodents could be reversible, since refeeding could repair the pathology. On the other hand, weight loss is a common feature in patients with more severe COPD. Complex factors, such as increased energy consumption, decreased food uptake by low grade inflammation, socio-economic factors and so on, are involved in weight loss. Weight loss in patients with COPD also increases the risk of exacerbation, hospitalization, and death. PMID- 27254942 TI - [Diagnosis and examination for COPD; medical interview/physical finding/ blood examination]. AB - Chronic obstructive pulmonary disease(COPD) is common disease. To diagnose COPD, pulmonary function test is required, however, usual physical examination and medical interview are both crucial. From both of them, we can acquire very important information and also this information will tell us much rather than pulmonary function test or images. In this article, we would like to summarize recent update about these topics. We focused on history taking from patients, examination of physical finding, and some possible biomarkers from blood examination. All of them may represent several important information of each patients, such as severity of disease, risk of future events, and also prognosis. For all physicians, it is necessary to evaluate these things. PMID- 27254943 TI - [Diagnosis and examination for COPD. Pulmonary function tests]. AB - Pulmonary function tests are essential for the diagnosis and management of COPD. It is important to understand the inspection method of tests and the interpretation of test results. The presence of a post-bronchodilator FEV1/FVC<0.70 confirms the presence of persistent airflow limitation and the diagnosis of COPD. On the other hand, the classification of severity of airflow limitation in COPD is based on %FEV1. In COPD patients, as airflow limitation worsens gas trapping and static hyperinflation occurs. These changes can be documented by lung volume measurement as increases in functional residual capacity, residual volume and total lung capacity. Measurement of diffusing capacity (DLco) provides information on the functional impact of emphysema in COPD. PMID- 27254944 TI - [Diagnosis and examination for COPD. Imaging]. AB - COPD is a chronic inflammatory disease with various comorbidities. Pulmonary emphysema and airway remodeling are two major pathological abnormalities in COPD, and these components can be quantified with imaging techniques such as chest computer assisted tomography (CT). Using CT images, we can evaluate local and regional information in the lung that cannot be obtained by other clinical indices such as pulmonary function tests. Furthermore, the alteration in pulmonary vasculature and chest wall including skeletal muscles and bones can be also evaluated in chest CT images. Recently, regional lung volume assessment using nonrigid image registration techniques or oxygenated oxygen-enhanced MR imaging are developed as functional imaging techniques to evaluate regional oxygenation or ventilation. PMID- 27254945 TI - [Distinguishing asthma from COPD]. AB - Asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. Asthma is characterized by airway inflammation, airway narrowing with reversibility, and hyperresponsiveness of airways. COPD has been associated with smoking and exposure to environmental fumes, which typically characterized by persistent airflow limitation and chronic inflammation of the airways. These differences are most apparent when young non-smoker with asthma and older smokers with COPD are compared. However, it would be difficult to differentiate asthma from COPD, especially in elderly who currently smoke or have a significant history of smoking. Furthermore, some patients exhibit characteristics of both diseases, this may represent a phenotype known as asthma-COPD overlap syndrome (ACOS). Therefore, the precise understanding of these diseases is important. PMID- 27254946 TI - [Asthma-COPD overlap syndrome (ACOS)]. AB - Asthma and COPD, once regarded as distinct disease entities, often overlaps especially in the elderly and smokers. GINA/GOLD joint document 2014 has proposed a clinical entity of ACOS (asthma-COPD overlap syndrome) characterized by irreversible airflow limitation with clinical features of both asthma and COPD, although evidences for definite diagnosis and treatment are limited. ACOS includes several different phenotypes such as severe asthma with airway remodeling, incomplete airflow reversibility as a consequence of childhood asthma and smoking, eosinophilic phenotype of COPD, and so on. Considering the therapeutic modalities currently available for asthma and COPD, it is important to identify the patients who respond well to inhaled corticosteroids. PMID- 27254947 TI - [Smoking cessation for COPD]. AB - Smoking cessation is the most effective intervention to prevent the annual decline in lung function in patients with chronic obstructive pulmonary disease. All primary healthcare providers should routinely ask all patients whether tobacco use is active or not, and advise tobacco users to stop smoking. In Japan a treatment of nicotine addiction with varenicline or nicotine patch has been started under health insurance coverage since 2006. About half of the patients taking varenicline could stop smoking. Education on the health risks of smoking in schools for younger ages is essential for prevention of COPD. PMID- 27254948 TI - [Pulmonary rehabilitation]. AB - Pulmonary rehabilitation commenced in Japan in 1957. However, the development of pulmonary rehabilitation took a long time due to the lack of the necessary health and medical services. Pulmonary rehabilitation is a comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, and behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health enhancing behaviors. The benefits of pulmonary rehabilitation include a decrease in breathlessness and an improvement in exercise tolerance. It is important that the gains in exercise tolerance lead to an increase in daily physical activity. PMID- 27254949 TI - [Home oxygen therapy and noninvasive ventilation for stable COPD]. AB - Chronic obstructive pulmonary disease (COPD) is the most common underlying disease of home oxygen therapy (HOT) and long-term noninvasive ventilation (NIV) in Japan. Although both have been increasingly used for stable COPD in clinical practice, there are numerous questions to be resolved with regard to the indication of these therapies. Here we briefly reviewed current indication and available evidence of HOT and long-term NIV for stable COPD. We also outline research agenda that should be investigated in future studies. PMID- 27254950 TI - [Nutrition management for COPD]. AB - Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory reaction of the lung and of the whole body, and pulmonary cachexia often occurs during the advanced stage. The effects of nutritional support upon the management of under nutrition in COPD remain controversial. However, a study of the effects of nutritional supplement therapy upon such patients with COPD has recently been published. The present report comprises a review of recent articles about the nutritional support of patients with COPD, especially those with cachexia, and a discussion about the roles of nutritional supplement therapy, focusing on exercise and treatment with ghrelin and vitamin D in the management of COPD. PMID- 27254951 TI - [Bronchoscopic treatments for COPD]. AB - Several non-surgical and minimally invasive bronchoscopic interventions, such as bronchoscopic lung volume reduction (BLVR) techniques, have been developed to treat patients with severe chronic obstructive pulmonary disease (COPD). BLVR has been studied for treatment in severe COPD patients with emphysema. BLVR with one way endobronchial valves is reported to be effective for patients with a heterogeneous emphysema distribution and without inter-lobar collateral ventilation. For the patients with collateral ventilation, and for the patients with homogeneous emphysema, BLVR with lung volume reduction coil has shown promising results. Targeted lung denervation(TLD) is a novel bronchoscopic intervention based on ablation of parasympathetic nerves surrounding the main bronchi. TLD seems to be effective for COPD with chronic bronchitis phenotype. This review gives a general overview of BLVR with one-way valve and lung volume reduction coil, and TLD. PMID- 27254952 TI - [Role of bronchodilators in therapy for COPD-mechanisms of LABA and LAMA on airway smooth muscle]. AB - Long-acting beta2-adrenergic receptor agonists (LABAs) and anticholinergics (LAMAs) are widely used clinically as therpy for COPD. Clinical reports have demonstrated that LABAs (salmeterol, formoterol, indacaterol, olodaterol, vilanterol) and LAMAs (tiotropium, glycopyrronium, umeclidinium, aclidinium) are useful to improving symptoms and lung function, and to reducing exacerbation and hospitarization. LABAs expect salmeterol are strong partial agonists, and LAMAs are non-specific antagonists. Ca2+ dynamics and Ca2+ sensitization contribute to relaxation of airway smooth muscle in these bronchodilators. LABAs act on orthosteric and allosteric sites on the beta2-adrenergic receptors. In contrast, LAMAs act not only on orthosteric site on the muscarinic receptors, but also allosteric site on the beta2-adrenergic receptors, leading to enhancing beta2 adrenergic action. Allosteric GPCR modulation is involved in the synergistic effects between LABAs and LAMAs. PMID- 27254953 TI - [LAMA/LABA fixed dose combination for treatment of COPD]. AB - Several new fixed-dose combination bronchodilators have been launched in the world, and 3 different types are now available in Japan. Assessing their efficacy relative to each other has not been performed yet. In the present manuscript, characteristics of glycopyrronium/indacaterol, umeclidinium/vilanterol and tiotropium/olodaterol were reviewed. In particular, changes in trough and peak forced expiratory volume in 1 second (FEV1), St George's Respiratory Questionnaire (SGRQ) total scores, and transitional dyspnea index (TDI) focal scores were reviewed in these bronchodilators. PMID- 27254954 TI - [Role of ICS/LABA on COPD treatment]. AB - In the treatment of chronic obstructive pulmonary disease (COPD), bronchodilators such as long acting muscarinic antagonist (LAMA) and long acting beta agonist(LABA) play key roles for improving respiratory function and symptoms, and reducing risk of exacerbation. However, inhaled corticosteroid (ICS), a key medicine for bronchial asthma, is limitedly used in COPD treatment. Japanese Respiratory Society recommends to use ICS for severe COPD patients who have been frequently exacerbated, because previous clinical studies indicated that ICS reduces exacerbation in moderate to severe COPD patients. Asthma sometimes overlaps with COPD, and symptoms of those patients are not well controlled by the bronchodilation therapy alone. Therefore, ICS/LABA or ICS/LAMA should be prescribed to those overlapped patients. Concentration of exhaled nitrogen oxide and percentage of peripheral eosinophil may be good biomarkers for discriminating the COPD patients who have good response to ICS treatment. PMID- 27254955 TI - [Effects of mucolytic agents and macrolides in the treatment of COPD]. AB - Mucolytic agents and macrolides have been used in the treatment of patients with chronic obstructive pulmonary disease (COPD). These drugs improve symptoms, such as sputum, and quality of life in COPD patients and reduce the frequency of COPD exacerbation. Mucolytic agents have various biological effects, such as reduction of mucin production, improvement of goblet cell hyperplasia and mucociliary transport, reduction of airway inflammation, and anti-oxidant and anti-viral effects. Similarly, in addition to antimicrobial effects, macrolides have biological effects, including reduction of mucin production and airway inflammation induced by airway infection, improvement of mucociliary transport, and anti-bacterial and anti-viral effects. These biological effects may be associated with clinical benefits of mucolvtic agents and macrolides in the treatment of COPD patients. PMID- 27254956 TI - [Pneumococcal vaccine and influenza vaccine for prevention of exacerbation in patients with COPD]. AB - Patients with chronic obstructive pulmonary diseases (COPD) are frequently exposed to infectious agents including influenza virus and Streptococcus pneumoniae. These infectious agents cause pneumonia and exacerbation of COPD. Prevention as well as anti-microbial treatments is critical for COPD. International guideline recommends that all COPD patients should be vaccinated against influenza virus. While pneumococcal vaccine is recommended for older and severe cases at present. Recently additive effect of pneumococcal vaccine and influenza vaccine are shown. PMID- 27254957 TI - [Improvement of physical activity in patients with COPD]. AB - Physical activity (PA) is defined as any bodily movement produced by skeletal muscles that results in energy expenditure beyond resting energy expenditure. Physical activity is an important clinical parameter closely related to morbidity and mortality in COPD. A self-report questionnaire is often subject to recall bias, correlates only poorly with objectively qualified PA, and does not provide an accurate estimate of free-living energy expenditure. In contrast, tri-axial accelerometers generate objective data in terms of quantifying steps or body movements performed over a period of a time. Low-intensity and home-based pulmonary rehabilitation with the feedback from using pedometer was effective in improving PA, and the improvements of physiological factors were correlated with increased walking time in stable elderly patients with COPD. PMID- 27254958 TI - [Comorbidities with COPD]. AB - Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder and age-related disorder associated with increased prevalence of comorbid diseases such as cardiovascular diseases, and pulmonary complications such as lung cancer. We described here the clinical significance of comorbid diseases with COPD and briefly review the mechanism in the production of comorbid diseases. PMID- 27254959 TI - [Management of older adults with COPD]. AB - In older adults, the clinical condition of COPD is complicated and treatment often becomes difficult, because of existence of multimorbidity, such as nutritional deficiencies, thinness, sarcopenia, osteoporosis, cardiovascular disease, depression and cognitive impairment. Consideration based on each of coexistence is needed in the management of older adults with COPD. In end period of COPD, sleep disorder, depressive state and decline of ADL are often shown, in addition to the respiratory symptoms, such as dyspnea, cough and sputum. Financial strain for the nursing cost and medical equipment cost tend to become big year by year, utilization of social resources (i.e. application of respiratory disabilities and an insurance of the elderly care) is need to be considered. PMID- 27254960 TI - [Lessons from the Hokkaido COPD cohort study]. AB - Hokkaido COPD cohort study is a carefully-designed, well-conducted, prospective observational 10 year-long study, which ended early in 2015. We have obtained a number of clinically-relevant novel findings, some of which are as follows. Severity of emphysema was highly varied even in those individuals whose airflow limitation is comparable. The annual change in forced expiratory volume in 1 second (FEV1) over 5 years was also widely varied with normal distribution among the subjects under appropriate treatment. Some patients maintained their pulmonary function for a long time, and others showed a rapid decline. Emphysema severity, but not pulmonary function, was independently associated with such an inter-subject variation in the annual decline in FEV1. When we explored any biomarkers for predicting the FEV1 decline, a lower leptin/adiponectin ratio alone emerged as an explanatory parameter for the rapid decline, and this was also confirmed in an independent Danish cohort study of different ethnicity. Monitoring of quality of life (QOL), using SGRQ scores, also provided interesting observations. The annual change in total score reflected that of FEV1 decline during the follow-up period. However, activity component in QOL deteriorated in almost all the subjects, while symptom component rather improved in many of the patients under appropriate treatment. PMID- 27254961 TI - [alpha1-Antitrypsin deficiency]. AB - alpha1-Antitrypsin deficiency (AATD) is the commonest genetic risk factor for developing chronic obstructive pulmonary disease. In 2015, AATD has been categorized as one of intractable diseases called "Nanbyo" in Japan. The prevalence of AATD is extremely low in Japanese compared with Caucasians in North America and Europe. According to recent nationwide epidemiological survey, the prevalence of AATD in Japan was estimated to be 24 patients with a 95% confidence interval. The mutation PI*S(iiyama) is commonly found in the Japanese patients with AATD, whereas PI*Z is the most frequent mutation associated with severe deficiency in Caucasians. The availability of AAT augmentation therapy in Japan is expected. This paper reviews the diagnosis and treatment in AATD. PMID- 27254962 TI - Nurses' Week 2016: Culture of Safety--It Starts With You. PMID- 27254963 TI - Nephrology Nursing and Education. AB - Professional nephrology nurses are responsible for their ongoing education and competency in their area of practice. ANNA has an additional opportunity for education for nephrology nurses at the 47th National Symposium to be held May 1 4, 2016, in Louisville, Kentucky. The Janel Parker Memorial Opening Session keynote speaker for the meeting will be Suzanne Miyamoto, PhD, RN, Senior Director of Government Affairs and Health Policy with the American Association of Colleges of Nursing. Her topic will be "Are We Practicing to the Fullest Extent? Licensure, Certification, and Education?" This session will help address educational competence in nephrology nursing. PMID- 27254964 TI - Professional Development: It Is Our Responsibility. PMID- 27254966 TI - Contrast-Induced Acute Kidney Injury: Comparison of Preventative Therapies. AB - Contrast medium is used daily for diagnostic and interventional procdures as a means to visualize blood vessels. The administration of contrast dye, however, can lead to an acute reduction in kidney function. This complication can impact length of hospital stay, risk of dialysis, and increased hospital mortality. Common preventative measures include N-acetylcysteine and intravenous hydration. The evidence reviewed revealed hydration to be the more effective treatment to reduce the risk of acute kidney injury. PMID- 27254965 TI - Relationship Between Age and Pre-End Stage Renal Disease Care in Elderly Patients Treated with Maintenance Hemodialysis. AB - Receipt of pre-end stage renal disease (ESRD) clinical care can improve outcomes for patients treated with maintenance hemodialysis (HD). This study addressed age related variations in receipt of a composite of recommended care to include nephrologist and dietician care, and use of an arteriovenous fistula at first outpatient maintenance HD. Less than 2% of patients treated with maintenance HD received all three forms of pre-ESRD care, and 63.3% received none of the three elements of care. The mean number of pre-ESRD care elements received by the oldest group (80 years and older) did not differ from the youngest group (less than 55 years), but was less than the 55 to 66 and 67 to 79 years groups; adjusted ratios of 0.93 (0.92 to 0.94; p < 0.001) and 0.94 (0.92 to 0.95; p < 0.001), respectively. A major effort is needed to ensure comprehensive pre-ESRD care for all patients with advanced chronic kidney disease (CKD), especially for the youngest and oldest patient groups, who were less likely to receive recommended pre-ESRD care. PMID- 27254967 TI - Perceptions of Culture of Safety in Hemodialysis Centers. AB - Staff members, physicians, nurse practitioners, and physician assistants from a sample of hemodialysis facilities in Network 6 (North Carolina, South Carolina, and Georgia) and Network 11 (Michigan, Minnesota, North Dakota, South Dakota, and Wisconsin) completed a 10-item assessment with modified questions from the Hospital Survey on Patient Safety Culture, with an emphasis on safety culture related to vascular access infections. A composite score was constructed, which was the average of the percent-positive scores of the items. Overall, scores were high, indicating a positive patient safety culture. Composite scores varied by role type, with nurses, patient care technicians, and other technicians reporting the lowest composite scores. Network 6 participants reported higher scores on two of the survey items. Fewer staff within a facility were associated with higher composite scores. PMID- 27254968 TI - A Comparison of Temporal Patterns of Fatigue in Patients on Hemodialysis. AB - This qualitative study describes the temporal patterns of fatigue found as part of a larger study designed to elicit a description of the experience and self management of fatigue for patients on hemodialysis. Two patterns of fatigue were identified. The first pattern, continuous fatigue, was characterized by participants who experienced fatigue at all times, which was their normal, baseline feeling. Within this group, two subgroups were identified. The second pattern of fatigue, post-dialysis fatigue only, was characterized by participants who experienced fatigue only after their hemodialysis session. This study is unique because it expands our knowledge about hemodialysis and fatigue by describing the patterns that fatigue follows over time from one hemodialysis session to the next. Insight into these phenomena could help ameliorate fatigue and allow nurses to tailor interventions for patients on hemodialysis. PMID- 27254969 TI - Kidney Transplantation in Patients with Human Immunodeficiency Virus Infection. PMID- 27254970 TI - Hemodialysis Catheter Care: Identifying Best Cleansing Agents. AB - In an attempt to create a standardized resource for cleansing both non-tunneled and tunneled hemodialysis catheters, it was discovered that all disinfectants are not compatible with all catheters. This article describes the process used to identify best practices for hemodialysis catheter care and steps taken to standardize practice throughout a hospital network. Standardized evidence-based practice preserves the integrity of catheters while allowing nurses to provide quality care to patients. PMID- 27254971 TI - Intimidating Behavior Among Healthcare Workers Is Still Jeopardizing Medication Safety. PMID- 27254972 TI - The Huddle: It's Not Just for Football Anymore. AB - Huddles are a wonderful team-building tool to enhance team function and efficiency. The Institute of Medicine (2011) report, The Future of Nursing- Leading Change, Advancing Health, identifies the need for collaborative healthcare teams. This is based on 14 years of research and evidence. Creating a team culture is identified as being essential to delivering high-quality patient care. Huddles are easy to complete and don't cost anything but a few minutes that are well worth their while! It's not often we get an opportunity to do so much with so little. So, 1, 2, 3, Hut; let's all go Huddle! PMID- 27254973 TI - Brilliant, Absolutely Brilliant: Reading to Dogs. PMID- 27254974 TI - Using Therapeutic Toys to Facilitate Venipuncture Procedure in Preschool Children. AB - Intravenous access procedures in children are considered to be one of the most stressful because it is invasive, and the use of needles generates anxiety, insecurity, and fear. Playful strategies using dolls and even the materials used for venipuncture can assist children in understanding, accepting, and coping with the procedure. Field research was developed on the applicability of the therapeutic toy in the preparation of preschool children for venipuncture procedure based on the protocol developed by Martins, Ribeiro, Borba, and Silva (2001) and Kiche and Almeida (2009). The study was done in a private hospital in Greater Sao Paulo, Brazil, with 10 children ages 3 to 6 years. Data were gathered through observation and questionnaires completed by the children's adult guardians. Before the activity, the children showed fearful facial expressions, used monosyllabic responses, and avoided looking at the health care professional. After the strategy of using therapeutic toy dolls and puppets, 40% of the children calmly accepted the venipuncture procedure, and 100% showed a change to their initial negative reaction, became more communicative and cooperative, and participated and interacted with researchers, even after the end of the activity and procedure. The strategy of therapeutic toys helps make an unfamiliar environment, strangers, and a procedure characterized as painful and difficult less stressful. Pediatric nurses are in a good position to use this resource to offer more humanized care to children. PMID- 27254975 TI - Sibling Experiences: Living with Young Persons with Autism Spectrum Disorders. AB - Like other young people, those with autism spectrum disorder (ASD) have an impact on siblings in both positive and negative ways. Research indicates positive attributes include maturity and responsibility; positive self-concept; less quarrelling and competition; admiration for the person with ASD; and satisfactory sibling relationships. Negative attributes include fear of frightening or violent behavior, decreased sibling intimacy, and social and emotional difficulties. However, most research relies on information from parents/teachers, rather than from siblings. Therefore, this qualitative descriptive study explored experiences of 11 brothers and 11 sisters living with a young person with ASD through audiorecorded semi-structured interviews. Analysis revealed the overall theme was contradiction. Participants recognized difficulties (decreased parental attention, extra responsibility, bothersome behaviors, communication difficulties) and positive aspects (became empathetic, loved and appreciated the child, realized the experience was life-changing) of living with a young person with ASD. Younger siblings frequently reflected on childhood experiences, wished they could play together, and mentioned what the young person could do. Adolescent siblings learned life lessons from the experience, talked about life changes when ASD was diagnosed, and seemed introspective and protective toward the young person with ASD. Male siblings often wished they played more often while growing up with the young person, and frequently mentioned the child/adolescent's aggressive behaviors; female siblings focused on relationship and communication difficulties of the young person ASD. Interventions to help siblings provide positive behavioral support, engage in developmentally appropriate play, and communicate reciprocally are warranted. Nurses can help parents understand siblings' perceptions and can encourage parents to support siblings. PMID- 27254977 TI - Measuring Perception: Purpose and Methods. PMID- 27254976 TI - Development of a Pediatric Fall Risk And Injury Reduction Program. AB - Fall prevention programs that include reliable, valid, and clinically tested screening tools have demonstrated more positive effects for adult and geriatric populations than those not including such assessment. In contrast, because falling is a natural part of growth and development for pediatric patients, progression toward effective prevention programs for this population has proven to be a challenge; a significant impediment is the lack of definition regarding what constitutes a reportable fall. This project explored pediatric health care providers' perceptions of patient falls in order to define a reportable pediatric fall and inform development of a prevention program. A concept analysis of defining attributes, antecedents, and consequences of pediatric falls from literature formed the basis for a set of questions; a convenience sample of 28 pediatric health care providers in an acute care hospital in New England participated in six moderated focus groups. Constant comparison method was used to code the qualitative data and develop themes. Participants unanimously agreed on several points; as expected, their years of experience in pediatric practice provided valuable insight. Three major themes emerged: patient characteristics, caregiver characteristics, and environmental characteristics. Based on factors identified by staff, a screening tool was adopted and integrated into the electronic medical record. Staff were actively engaged in developing definitions, selecting tools, and identifying next steps toward a comprehensive fall reduction program for their patients. As a result, they have embraced changes and advocated successfully for endorsement by the organization. PMID- 27254978 TI - Mentoring Practice and Mentoring Benefit 1: Welcoming and Belonging--An Overview and Application to Practice Using Mentoring Activities. PMID- 27254979 TI - Promoting Children's Health-Related Quality of Life. AB - Pediatric health care practitioners have the ability to impact a child's HRQoL. Children's HRQoL is well documented in the literature as an important matter for children receiving health care, with research to support its significance in their lives. Children and adolescents have much to teach practitioners, and listening to their perspectives of health care experiences has a direct effect on the clinician's ability to improve their HRQoL. Pediatric practitioners focused on providing high-quality patient care must incorporate the goal to positively influence children's HRQoL. PMID- 27254980 TI - KIDS CARE: A Behavioral Model To Strengthen Patient and Family Partnerships. AB - Patient- and Family-Centered Care is a core value of The Children's Hospital of Philadelphia (CHOP). Satisfaction/ experience data are closely tracked to assist in determining if hospital staff are partnering effectively with patients and families. When opportunities for improvement were identified within the Nursing Department, an existing institutional model, KIDS CARE, was used to promote change. KIDS CARE was developed to teach and reinforce respectful behaviors for nurses initiating partnerships with patients and families. The Patient Satisfaction Committee partnered with the Family Advisory Council and Shared Governance Council to revise this model to help achieve the goals of improving quality of care. Next steps involved educating patients, families, and staff using innovative multimodal strategies. By engaging in this renewed commitment to Patient- and Family-Centered Care, systems and structures were developed to keep KIDS CARE relevant and make strides toward improved outcomes for patients and families. PMID- 27254981 TI - Children's Specialized Hospital and GetWellNetwork Collaborate to Improve Patient Education and Outcomes Using an Innovative Approach. AB - Patient education in a pediatric setting is unique. There are different patient ages, degrees of learning, and diagnoses to take into account when educating children and their families. A new and innovative trend in practice called Interactive Patient Care (IPC) integrates technology into care processes to advance pediatric nursing education and patient and family satisfaction. Children's Specialized Hospital is the first pediatric rehabilitation hospital to develop and implement this type of program using an IPC platform from the GetWellNetwork. With the implementation of the GetWellNetwork, Children's Specialized Hospital has achieved positive results in patient satisfaction, health care utilization, quality, and safety measures. PMID- 27254983 TI - ALP SEEKS IMPROVEMENTS TO WORKERS' PROTECTIONS. PMID- 27254982 TI - Excessive Hunger and Weight Loss In a Healthy Teen. PMID- 27254984 TI - The Lost Souls: How Australia's Asylum Seeker Policy is Damaging Children. PMID- 27254985 TI - IMPROVING CARDIOVASCULAR NURSE-LED HEALTH SERVICES. PMID- 27254986 TI - WALK THE TIGHTROPE IN SAFETY AND IN HEALTH. PMID- 27254987 TI - WORKING LIFE: ROSE MCRCOHAN. PMID- 27254989 TI - DIABETES, OLDER PEOPLE AND EXERCISE: RECOMMENDATIONS FOR HEALTH PROMOTION PROGRAMS. PMID- 27254988 TI - PREGNANCY, CROHN'S DISEASE AND AZATHIOPRINE: A CASE STUDY AND LITERATURE REVIEW. PMID- 27254990 TI - GENERAL PRACTICE NURSE DIABETES CARE: WHAT DO PATIENTS EXPERIENCE? PMID- 27254991 TI - INSULIN THERAPY AT PRIMARY SCHOOL. PMID- 27254992 TI - SIMULATED PATIENTS ENHANCE DISCHARGE PROCESSES FOR PATIENTS WITH TYPE 2 DIABETES. PMID- 27254993 TI - MANAGING DIABETES AND MENTAL ILLNESS. PMID- 27254994 TI - AN INNOVATIVE ONLINE SELF-MANAGEMENT INTERVENTION FOR YOUNGER ADULTS WITH TYPE 1 DIABETES. PMID- 27254995 TI - FACTORS INFLUENCING BREASTFEEDING WOMEN LIVING WITH TYPE 1 AND TYPE 2 DIABETES. PMID- 27254996 TI - DIABETES HEALTH AT THE BEDSIDE: WHAT CAN YOU DO? PMID- 27254997 TI - DABETES NURSE PRACTITIONER: CONVERTING PRACTICE INTO VALUE. PMID- 27254998 TI - DIABETES AND MENTAL HEALTH: A HOLISTIC APPROACH IS NEEDED. PMID- 27254999 TI - THE WOMEN'S WELLNESS WITH TYPE 2 DIABETES PROGRAM. PMID- 27255000 TI - PERSON-CENTRED CARE IN DIABETES: A MUST HAVE. PMID- 27255001 TI - IMPROVING ACCESS AND SUPPORT FOR PEOPLE WITH TYPE 2 DIABETES COMMENCING INJECTABLE THERAPY. PMID- 27255002 TI - ENS DESERVE RECOGNITION. PMID- 27255003 TI - ACCEPTING A DIFFERENT POINT OF VIEW. PMID- 27255004 TI - AGED CARE WORKFORCE REPUTATION. PMID- 27255005 TI - CUTS TO CLIMATE CHANGE. PMID- 27255006 TI - THE AUSTRALIAN OF THE YEAR. PMID- 27255007 TI - A Winning Strategy: The ADA's Health Policy Institute. PMID- 27255009 TI - Hey, Did You Hear Tommy Retired? PMID- 27255010 TI - A Case for Orthodontic Involvement in Temporomandibular Disorders. PMID- 27255012 TI - Principle and Practice in Ethics and Morality--Part Two. PMID- 27255011 TI - It Follows: A Q & A on "What Works". PMID- 27255013 TI - By and For Our Members: The 2016 MDA President's Interview. PMID- 27255014 TI - What is this Prescription Monitoring Program About? Read on and Pay Attention! PMID- 27255015 TI - The Prescription Monitoring Program (PMP): The How and Why You Should Do It Today. PMID- 27255016 TI - [On organizing the 38th annual meeting of the Japanese Society for Clinical Toxicology]. PMID- 27255017 TI - [Dangerous marine animals. Food poisonings due to marine biotoxins of fishes]. PMID- 27255018 TI - [Risk assessment of rescue helicopter or ambulance transport of patients ingesting hazardous volatile materials]. AB - INTRODUCTION: In cases of transport by rescue helicopter or ambulance of patients having ingested hazardous substances, medical personnel may be at a certain risk of inhaling the substances. However, few reports have addressed such risk of causing secondary casualties. PURPOSE: This simulation study aimed to assess the risk of inhalation of hydrogen sulfide and chlo-opicrin in the cabin of a helicopter or an ambulance transporting a patient who has ingested calcium polysulfide or chloropicrin, which were previously reported to cause secondary casualties. METHOD: Concentrations of hydrogen sulfide and chloropicrin were assessed on the following as-umptions :The patient ingested 100 mL of the causative or original chemical. All chemical substances reacted with the gastric juice or were thoroughly vomited and evaporated uniformly within the cabin space of the helicopter or ambulance. Environmental conditions were 20 *degrees at 1 atmosphere of pres-ure in a 5 m3 cabin volume in the helicopter and a 13.5 m3 cabin volume in the ambulance. RESULTS: In the case of calcium polysulfide ingestion which produced hydrogen sulfide, its concen-ration reached 774 ppm in the helicopter and 287 ppm in the ambulance. For chloropicrin ingestion, the concentrations were 4,824 ppm and 1,787 ppm, respectively. DISCUSSION: The simulated concentration of hydrogen sulfide was more than 500 ppm in the heli opter, which may lead to respiratory paralysis and death. The simulated concentration of chloropicrin was more than 300 ppm, which has a risk of death within 10 minutes. Currently, as far as Japanese laws are concerned, there are no restrictions requiring pretransport assessment or setting criteria for transporting patients who might have ingested hazardous substances that could cause secondary casu-lties when vomited. CONCLUSION: When patients who might have ingested hazardous chemicals are transported, it is important to recognize the risk of causing secondary casualties by vomiting the chemicals. PMID- 27255019 TI - [Venomous stings: Especially jellyfish stinging cases]. PMID- 27255020 TI - [The current situation of aggravated intoxication with "kiken" drugs (law-evading drugs)]. AB - The intoxication caused by "kiken" drugs (law-evading drugs), such as synthetic cannabinoids, cathinones, and methoxetamine, has recently increased in Japan. We retrospectively examined the characteristics of patients poisoned with the "kiken" drugs. We included patients who presented at the emergency department at the Tokyo Metropolitan Bokutoh Hospital from January 2011 to December 2014. Eighteen patients admitted between January 2011 and December 2013 were included in the early period group and 10 patients admitted between January and December 2014 were categorized into the late period group. The number of the patients transported to our emergency department between 2011 and 2014 increased annually. Patients were mainly admitted between May and October 2014; no patients were admitted after November 2014. The patients' age, history of previous mental disease, habitual use, Triage DOA results, serum creatinine values on admission, and respiratory management differed significantly between the groups. However, the median serum creatinine values of both groups on admission were within the normal level. Patients poisoned with the "kiken" drugs showed more severe symptoms, higher rate of habitual use, and higher average age. The annual increase in the number of the patients observed thus far is expected to decrease in the future. Maintenance of the law and expansion of medical institutions that treat patients addicted to the "kiken" drugs are warranted. PMID- 27255021 TI - [Bowel obstruction-induced cholinergic crisis with progressive respiratory failure following distigmine bromide treatment]. AB - A 54-year-old female experienced rapid respiratory failure while being transported in an ambulance to our emergency department for evaluation and management of constipation and abdominal pain. The patient was on treatment with distigmine bromide for postoperative urination disorder and magnesium oxide for constipation. Increased salivary secretions, diminished respiratory excursion, type 2 respiratory failure (PaCO2 : 65 mmHg), low serum cholinesterase, and hypermagnesemia were detected. Imaging studies revealed that the patient had bilateral aspiration pneumonia, fecal impaction in the rectum, and a distended colon causing ileus. The patient was mechanically ventilated and was weaned off the ventilator on day 3. Therapeutic drug monitoring after discharge revealed that the serum level of distigmine bromide on admission was markedly elevated (377.8 ng/mL vs. the normal therapeutic level of 5-10 ng/mL). Distigmine bromide induced a cholinergic crisis with a resultant increase in airway secretions and respiratory failure. In this particular case, orally administered distigmine bromide was excessively absorbed because of prolonged intestinal transit time secondary to fecal impaction and sluggish bowel movement; this caused a cholinergic crisis and hypermagnesemia contributing to respiratory failure. Clinicians should be aware that bowel obstruction in a patient treated with distigmine bromide can increase the risk of a cholinergic crisis. PMID- 27255022 TI - [Acute valproic acid overdose causing only somnolence and stagger despite the extreme hyperammonemia: A case report]. PMID- 27255023 TI - [Three cases of acute serotonin syndrome due to psilocybin mushroom poisoning]. PMID- 27255024 TI - [Dealing with poisoning patients with borderline personality disorder]. PMID- 27255025 TI - [Sodium bicarbonate]. PMID- 27255026 TI - [Lung injury and safety measures for household waterproofing sprays]. PMID- 27255027 TI - [Practical analysis of toxic substances useful for clinical toxicology: From sample preparation to screening. Typical extraction method for biological samples]. PMID- 27255028 TI - [APAMT 2015]. PMID- 27255029 TI - [Investigation of acute poisoning of cosmetics based on JPIC inquiries]. PMID- 27255030 TI - [Changes of the mitochondrial DNA copy number and the antioxidant system in the PBMC of hepatocellular carcinoma]. AB - OBJECTIVE: To investigate the relationship between the changes of the copy numbers of mtDNA in peripheral blood mono-nucle- ar cell(PBMC) and the disordered of antioxidant capacity of hepatocellular carcinoma (HCC) patients. METHODS: The Ficoll Hypaque method was used to isolate the PBMC from blood specimens. The ND1 gene of the mitochondrial was amplified by real-time PCR; meantime beta-actin was served as a quantitative standard marker; the difference of mtDNA copy number in PBMC was compared between HCC and healthy control group. The level of reactive oxygen species (ROS) in PBMC was determined by flow cytometry. The change of total antioxidant capacity (T- AOC) of plasma was detected by the biochemistry examination. RESULTS: The copy numbers of ND1 gene in PBMC of HCC was 73% that of the healthy control group,which suggested a decrease of the copy numbers of mtDNA in HCC. The levels of ROS of PBMC in HCC was (417. 82 +/- 110.62) and (301.82 +/- 75.54) in control group, which showed that the levels of ROS of PBMC in HCC were significant higher than that in control group (P < 0.01).Plasma T-AOC in HCC was (1.30 +/- 0.85), and (3.20 +/- 1.62) in control. The T-AOC of plasma of HCC was significantly lower than in control group (P < 0.01). CONCLUSION: There was a certain relationship between the decrease of the copy numbers of mtDNA and the disordered antioxidant capacity in hepatocellular carcinoma, which may be associated with the development of hepatocellular carcinoma. PMID- 27255031 TI - [The effect of cold air and dust weather on the content of IL-6,8- iso-PGF2alpha and 11-DH-TXB2 in urine]. PMID- 27255032 TI - [Effect of hydrogen sulfide on oxidative stress and endoplasmic reticulum stress in diabetic cardiomyopathy]. AB - OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on oxidative stress and endoplasmic reticulum stress (ERS) in a rat model of diabetic cardiomyopathy (DCM). METHODS: Thirty male SD rats were randomly divided into control group, diabetes group and treatment group( n = 10). Intraperitoneal injection of streptozotocin was utilized to establish a rat model of DCM. The rats with DCM in treatment group were intraperitoneally injected with NaHS solution. After treated for 12 weeks, the hearts isolated from rats were perfused on a langendorff apparatus. The ventricular hemodynamic parameters were measured. The ultrastructures of myocardium were observed using electron microscopy. The content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in myocardial tissue were determined by spectrophotometry. The expressions of C/EBP homologous protein( CHOP), glucose regulated protein 78 (GRP78) and Caspase 12 at mRNA level in myocardium were detected using RT-PCR. RESULTS: Compared with control group, the cardiac function and myocardial ultrastructure were damaged obviously in diabetic rats. In myocardial tissue, the content of MDA was increased, while the activities of SOD and GSH-Px were decreased. CHOP, GRP78 and Caspase 12 mRNA expressions were increased significantly. Compared with diabetes group, cardiac function and myocardial ultrastructure damage were improved in treatment group. The content of MDA was decreased, while the activities of SOD and GSH-Px were increased significantly. The mRNA levels of CHOP, GRP78 and Caspase 12 were increased. CONCLUSION: H2S can protect myocardium in diabetic rats, maybe it is related to reduce oxidative stress damage and inhibition of the ERS-induced apoptosis pathway. PMID- 27255033 TI - [Expression and significance of Nrf2/ARE pathway ralated factors in the HepG2 cell model of steatosis]. AB - OBJECTIVE: To explore a new method of establishing HepG2 cell model of steatosis and observe the expression and significance of nuclear factor erythroid-2p45 related factor 2(Nrf2)/antioxidative response element (ARE) pathway related factors in HepG2 cells of steatosis. METHODS: HepG2 cells were induced with DMEM containing 25% fetal bovine serum, 0.1% MCT/LCT Fat Emulsion and 0.1 mmol/L free fatty acid (FFA) at different stages and the control group cells were cultured with normal DMEM medium. After the cell models were successfully established, lipid droplets in cytoplasm were observed with Oil Red 0 staining, and the triglyceride (TG) accumulation in HepG2 cells were tested by biochemical assay. Intracellular reactive oxygen species (ROS) concentration were detected by flow cytometry. Nitric oxide (NO), superoxide dismutase(SOD), malonyldialdehyde(MDA) and glutathione peroxidase(GSH-Px) were tested by biological reagent kit, while the protein expression of nuclear factor erythroid-2p45-related factor 2(Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1(NQO1) were analyzed by Western blot. RESULTS: Compared with that in the control group, red cytoplasmic lipid droplets were visible in model group; TG,ROS, NO, MDA concentration (P < 0.05, P < 0.01) and the protein expression of Nrf2, HO-1 and NQO1 (P < 0.05, P < 0.01)were significantly higher in model group, while SOD, GSH Px concentration reduced significantly (P < 0.01). CONCLUSION: The in vitro cell model of steatosis and oxidative stress was successfully established. The activation of Nrf2/ARE pathway related factors maybe relevant to the overreaction of oxidative stress in HepG2 cells of steatosis. PMID- 27255034 TI - [Effects of rapamycin on amyloid beta-protein induced impairments of working memory and synaptic plasticity in rats]. AB - OBJECTIVE: The present study investigated the effects of rapamycin on Abeta1-42 induced deficits in working memory and synaptic plasticity. METHODS: After bilateral hippocampal injection of Abeta1-42 and rapamycinin rats, spontaneous alternation in Y-maze and in vivo hippocampal long-term potentiation (LTP) of rats were recorded. All data were analized by two-way repeated measures analysis of variance (ANOVA). RESULTS: (Hippocampal injection of Abeta1-42 alone impaired working memory of rats; (2) Rapamycin did not affect working memory of rats, but alleviated Abeta1-42-induced working memory deficits, compared with Abeta1-42 alone group; (Abeta1-42 remarkably suppressed in vivo hippocampal LTP of fEPSPs in the CA1 region; (4) Pretreatment with rapamycin prevented Abeta1-42-induced suppression of LTP. CONCLUSION: These data indicates that rapamycin could protect against Abeta1-42-induced impairments in working memory and synaptic plasticity in rats. PMID- 27255035 TI - [The expression of Calbindin and Parvalbumin in auditory pathway of kit gene mutated C57BL/6J mouse]. AB - OBJECTIVE: To observe the expressions of Calbindin(CB) and Parvalbumin (PV), the two calcium-binding protein, in auditory pathway in mice of wild type C57BL/6J and kit+/kitW- 2Bao, a kit gene mutant. METHODS: Six mutated kit gene kit+/kitW- 2Bao mice and 6 wild type C57BL/6J (B6) mice were anaesthetized i. p. with chloral hydrate. After the mice were fixed by heart perfusion, the brains were removed and coronal sections were cut with a freezing microtome. RESULTS: We found that wild type mice had significant expressions of PV on ventral cochlear nucleus, anterior part (AVCN), ventral cochlear nucleus, posterior part (PVCN), inferior colliculus (IC) and auditory cortex (AC). CB was expressed in wild type mice on PVCN and nucleus of the trapezoid body (Tz). The mutant of kit gene induced the less expression of PV on PVCN, IC and AC (P < 0.01), but increased the expression of Tz (P < 0.01). CB could not be observed on PVCN in mutant mice, and the expression of AC was increased( P < 0.01). CONCLUSION: CB and PV has differential expression level in auditory pathway. Since mutated kit gene can affect expression of PV on PVCN, IC, Tz and AC, as well as CB on PVCN and AC, it suggests that the mutation of kit gene can affect the advanced function of central nervous system in auditory pathway. PMID- 27255036 TI - [The effect of hypoxia on pulmonary artery smooth muscle cells two pore domain potassium channels TASK-1 and the regulation of non-receptor tyrosine kinases]. AB - OBJECTIVE: To investigate the effect of hypoxia on the human pulmonary artery smooth muscle cells two pore domain potassium channels TASK-1 and the regulation of non-receptor tyrosine kinase c-Src in this process. METHODS: The cultured human pulmonary artery smooth muscle cells (hPASMCs) were divided into: normal group, hypoxia 30 minute group, hypoxia 6 hours group and hypoxia 48 hour group, and hypoxia 48 hour + PP2 group, hypoxia 48 hour + PP3 group, hypoxia 48 hour + bpV group. Flow cytometry was used to analyze the cell cycle, RT-PCR and Western blot technique were carried out to detect the expression changes of TASK-1 mRNA and protein in different groups. RESULTS: (1) Cell Cycle Show: Compared with normal control group, with prolonged hypoxia, the percentages of hPASMCs in S phases of cell cycle were increased. While compared with hypoxia 48 hour group, the percentages of hypoxia 48 hour + PP2 group hPASMCs in S phases of cell cycle were decreased. The expression of TASK-1 mRNA on hPASMCs in acute hypoxia 6 hour group was increased, while the expression of TASK-1 protein on hPASMCs in the acute and chronic hypoxia group was decreased, and the expression of TASK-1 mRNA on hPASMCs in the chronic hypoxia group was decreased; After pre-incubation of a potent and selective inhibitor of the Src family of protein tyrosine kinases PP2, the expression of TASK-1 mRNA and protein in hypoxia 48 hour group was increased, however after pre-incubation of the inhibitor of the Src family of protein tyrosine phosphatase bpV, the expression of TASK-1 protein in hypoxia 48 hour group was decreased. CONCLUSION: Hypoxia promotes human pulmonary artery smooth muscle cell proliferation, and non-receptor tyrosine kinase c-Src may participate in the expression of two pore domain potassium channels TASK-1 regulated by hypoxia. Therefore, we hypothesized that TASK-1 channels and c-Src participatein the acute and chronic hypoxic human pulmonary vasoconstriction. PMID- 27255037 TI - [Effects of glycyrrhizic acid beverage on exercise performance of fe- male undergraduates with moderate endurance training and its mechanism]. PMID- 27255038 TI - [The effects of sacral nerve root electrostimulation on the colon function and its mechanisms in a rat model of spinal cord injury]. AB - OBJECTIVE: To study the effects of sacral nerve root electrostimulation (SNS) on the colon function and its mechanisms in rats with spinal cord injury (SCI). METHODS: One hundred and four Wistar rats were divided into three groups: A, B and C. A group ( n = 24) was divided into three subgroups (n = 8) for studying the bioelectricity: Normal group (NG), SCI group (SCI) and SCI group with SNS(SNS); B group( n = 24) was divided into three subgroups( n = 8) for studying the colon motility: NG, SCI and SNS. C group( n = 56) were divided into three groups for studying the change of morphology and neurotransmitters(SP and VIP): NG (n = 8), SCI (n = 24), and SNS (n = 24) . In SCI and SNS, included of three subgroups: 24, 48, 72 h after spinal cord injury (n = 8). RESULTS: In SCI group, the activity of bioelectricity in proximal and distal colon was reduced; the colon motility was lessened, and colon mucosa appeared different degree of damage; cell-cell connections between intestinal epithelial cells were destroyed. The expressions of substance P(SP) and vasoactive intestinal peptide (VIP) in colon were decreased obviously. SNS was found to activate the bioelectricity, promote the colon motility, improve the intestinal mucosal, and increase the expressions of SP and VIP. Conclusion: SNS can activate the peristalsis, rehabilitate the motility of denervated colon, protection of the intestinal mechanical barrier between intestinal epithelial cells and tight junction, rebuild the colon function through activating the bioelectricity and increase the expressions of SP and VIP. PMID- 27255039 TI - [Protective effects of silybin . ursodeoxycholic acid evaporated co- precipitate on CCl4-induced acute liver injury in mice]. PMID- 27255040 TI - [The application of in vivo multi-channel recording methods in the studies of the affective pain in rats]. AB - OBJECTIVE: To record the electrical activities of Antirior cingulate cortex (ACC) neurons by in vivo multi-channel recording methods using the model of complete freund's adjuvant (CFA) induced conditioned place avoidance (C-CPA), which has been set up in our previous studies. METHODS: The electrode was self-made and the CPA responses were recorded by in vivo multi-channel recording method. RESULTS: (1) The electrical activities of ACC neurons could be successfully recorded by the self-made electrode. (2) Before or after the injection of CFA, rats were respectively conditioned to the different place. The firing rates of ACC neurons in the CFA-paired place vs that in the non-CFA-paired place was (0.853 +/- 1.377) imp/s vs (0.221 +/- 0.971) imp/s (P < 0.05, n = 26). (3) The CPA responses in the CFA-paired place vs that in the non-CFA-paired place were (303.55 +/- 61.77)s vs (140.32 +/- 33.52)s(P < 0.05, n = 6). CONCLUSION: The firing rates of rACC (rostral Anterior Cingulate Cortex) neurons were involved in the occurrence of the affective pain. PMID- 27255041 TI - [Construction of T vectors based on Xcm I recognition site and optimization of PCR fragments for ligation]. AB - OBJECTIVE: To construct T vectors based on Xcm I recognition site and optimize the PCR fragments for its ligation. METHODS: We firstly cloned the human histone H4 cDNA containing one Xcm I recognition site at both its 5' and 3' end into pCDNA 3.0 vector and then generated T vector with pCDNA 3.0 backbone by cutting the recombinant plasmid with Xcm I. To increase the ligation efficiency, the primers were firstly phosphorylated before DNA fragments amplification and then the PCR products were treated with Taq DNA polymerase and dATP after PCR amplification. Two DNA fragments with the length of 312 bp and 1 329 bp were ligated to it and the ligation mixture was transformed into E. coli DH5alpha competent cells and the positive rates of the transformants were evaluated by PCR and DNA agarose gel electrophoresis. RESULTS: Our results showed that the T vector produced by our method could ligate to the target DNA fragments with high efficiency. Besides, the phosphorylation state of the primers used for PCR amplification is also an important factor determining the cloning efficiency. What's more, as for longer DNA fragments, retreatment with Taq DNA polymerase and dATP after PCR amplification and purification could improve the ligation efficiency significantly. CONCLUSION: Our protocol may overcome the dependence on blue/white screening to get positive clones and provide a potent way to generate T vectors and ligate them to the target PCR fragment. PMID- 27255042 TI - [Effect of total flavonoids of astragalus on endoplasmic reticulum chaperone, calumenin and connecxin 43 in suckling mouse myocardium with myocarditis caused by coxsackievirus B3]. AB - OBJECTIVE: To investigate the effect of total flavonoids of astragalus on the expression of endoplasmic reticulum chaperone, calumenin and connecxin 43 (CX43) in suckling mouse myocardium with myocarditis caused by coxsackievirus B3 (CVB3). METHODS: The primary culture of suckling mouse myocardium cells were randomly divided into control group, CVB3 infected group and total flavonoids of astragalus group. Firstly, to confirm the identity of the suckling mouse myocardium, alpha-SMA was monitored by immunohistochemistry method. Then the protein expression changes of endoplasmic reticulum chaperone-glucose regulatory protein 78 ( GRP78), calumenin and CX43 were detected by Western blot. RESULTS: (1) Compared with that of the control group, the GRP78 expression level in CVB3 infected group was improved, the expression levels of calumenin and CX43 were all reduced. (2) Compared with that of CVB3 infected group, GRP78 expression level was decreased, and the expression levels of calumenin and CX43 were increased in total flavonoids of astragalus group. CONCLUSION: CVB3 infection may cause endoplasmic reticulum stress of rat myocardium cells by increasing the expression of GRP78 and decreasing the expression of calumenin and CX43. On the other hand, total flavonoids of astragalus can reduce the expression of GRP78 and increase the expression of calumenin and CX43.The results of this experiment may be closely related to the effects of anti-arrhythmia with viral myocarditis caused by CVB3. PMID- 27255043 TI - [The influence of the aerobic endurance training on the skeletal muscular mitochondria function and PI3K-Akt protein expression]. AB - OBJECTIVE: To determine the role of phosphatidylinositol 3-kinase--protein kinase B (PI3K-Akt) signaling pathway in the pro- tective effect of aerobic endurance training on the skeletal muscular mitochondria. METHODS: Thirty-six rats were randomly divided into three groups( n = 12): control group, aerobic endurance training group and one-time exhaustive group. After the intervention, the quadriceps femoris muscle sample was obtained to detect the mitochondrial membrane potential( MMP), the activities of succinate dehydrogenase (SDH) and cy- tochrome coxidase (COX), and the protein levels of p-PI3K and p-Akt. RESULTS: Compared with the control group, the levels of mitochondrial membrane potential, the activities of succinate dehydrogenase and cytochrome coxidase, and the protein levels of p-PI3K and p-Akt were all significantly decreased in the one time exhaustive group (P < 0.05). However, all the above was partially reversed in the endurance training group (P < 0.05), and there was no obvious difference with the control group (P > 0.05). CONCLUSION: Aerobic endurance training plays an important role in the protective effect on the skeletal muscular mitochondria, the mechanism may be related to activation PI3K-Akt signaling pathway. PMID- 27255044 TI - [Studies on external auditory canal injury in rabbits under simulated 50 mnitrogen-oxygen saturation diving and protective effect of compound aluminium acetate solution]. PMID- 27255045 TI - [The effects of graphene quantum dots on hematopoietic system in rats]. AB - OBJECTIVE: To study the effects of graphene quantum dots (GQDs) on hematopoietic system in rats. METHODS: Thirty male SD rats were randomly divided into three groups (n = 10): control group, high dose group (10 mg/kg . d), low dose group (5 mg/kg . d), The rats in experimental group were intravenous injected with GQDs for 28 days and those in control group were injected with normal saline at the same volume. Routine blood and the function of liver and kidney were detected by instrument analysis. The cycle and apoptosis of bone marrow mononuclear cells (BMCs) were detected by FCM. The other three only healthy male SD rat bone marrow mononuclear cells (BMCs) were cultured by joining GQDs for 24 h, 48 h,72 h in vitro, the proliferation was assayed by CCK-8, the content of granulocyte macrophage colony stimulating factor (GM-CSF) from cultural supernatants were detected by ELISA. RESULTS: The amount of red blood cell and concentration of hemoglobin from experimental group were increased significantly compared with those of control groups (P < 0.05), the concentration of triglyceride and high density lipoprotein were decreased. DNA synthesis period was prolonged (P < 0.01), there was no significant difference in apoptosis. BMCs were promoted proliferation clearly after using GQDs for 72 h (P < 0.05). The content of GM-CSF was increased (P < 0.01) . CONCLUSION: GQDs may promote hematopoietic function in rats. PMID- 27255046 TI - [Dynamic changes of TGF-alpha and TGF-beta1 in rats with liver cirrhosis induced by multiple pathogenic factors]. AB - OBJECTIVE: To explore the dynamic changes of transforming growth factor-alpha (TGF-alpha) and transforming growth factor-beta1 (TGF-beta1) of liver cirrhosis induced by multiple pathogenic factors in rats. METHODS: Animals in the cirrhosis group were fed a mixture of maize flour, lard, cholesterol and alcohol plus subcutaneously injection with carbon tetrachloride (CCl4), the CCl4(0.5 ml/100 g . w) was injected at the first day of experiment and the 40% CCl4oil solution (0.3 ml /100 g . w) was injected at an interval of three days. The thirty-six male SD rats were randomly divided into liver cirrhosis group of the 4th, 6th and 8 th week, and normal control group of the 4th, 6th and 8th week. The contents of alanine transferase (ALT), endotoxin, tumor necrosis factor-alpha (TNF-alpha) and homocysteine (Hcy) in plasma were evaluated. Histopathological changes of the liver were observed under microscope with the staining of HE. The expressions of TGF-alpha and TGF-beta1 were analyzed by the method of immunohistochemistry. RESULTS: Compared with the corresponding normal control group, the levels of ALT, endotoxin, TNF-alpha and Hcy in plasma were gradually significantly increased in liver cirrhosis group of the 4th, 6th and 8th week (P < 0.05); the expression of TGF-alpha in the liver tissues was significantly increased at the 4th week (P < 0.05); the expression of TGF-beta1 in the liver tissues was gradually significantly increased in every model group (P < 0.05). CONCLUSION: In the formation process of cirrhosis, the expression of TGF-alpha was increased in liver of cirrhosis group at the 4th week, and later it was suppressed; the expression of TGF-beta1 was continuously increased. The characteristic dynamic changes of TGF-alpha and TGF-beta1 might be related to sustained endotoxemia, the high level of TNF-alpha and hyperhomocysteinemia. PMID- 27255047 TI - [Effects 'of beta3 adrenoceptors on the contractility of rat thoracic aorta smooth muscle and the mechanism]. AB - OBJECTIVE: To observe the effect of beta3adrenoceptors (beta3-AR) activation on rat thoracic aorta smooth muscle contractility and the possible related mechanism. METHODS: The endothelium removed thoracic aorta was pre-contracted with 30 mmol/L KCl physiological saline solution (PSS). Then the tension of the thoracic aorta was recorded in presence of BRL37344 (BRL) to determine the action of beta3-AR. The tension of the thoracic aorta was also recorded in the presence of Propranolol (PRA), SR59230A (SR), L-NNA, H-89 and Iberiotoxin (IBTX) respectively to reveal the underling mechanism of beta3-AR activation on rat vascular smooth muscle. Immunohistochemistry was adopted to confirm the existence and the distribution of beta3-AR in rat thoracic aorta. RESULTS: The results showed that: (1) The thoracic aorta was relaxed by beta3-AR activation, with a relaxation percentage of (10.59 +/- 0.79). (2) beta3-AR was expressed in both endothelial and smooth muscle layer in thoracic aorta sections of rats. (3) PRA did not block the effect of BRL on the thoracic aorta. The relaxation actions of BRL could be antagonized by pre-incubating the thoracic aorta with SR. (4) L-NNA (a NOS inhibitor) and H-89 (a PKA inhibitor) reversed the relaxation effect of BRL on vascular smooth muscle. (5) The effect of BRL was decreased after application of Ibriotoxin (IBTX), a large conductance calcium dependent potassium channel blocker. CONCLUSION: The results confirmed that activation of beta3-AR led to relaxation of thoracic aorta smooth muscle. The relaxation action of beta3 AR on smooth muscle of rat thoracic aorta was related to activation of NOS and PKA signaling pathway. Large conductance Ca2+-K+ channels were involved in the relaxation action of beta3-AR activation on rat thoracic aorta smooth muscle. PMID- 27255048 TI - [Effect of matrine on cell apoptosis and proliferation and the apoptosis related proteins of human medulloblastoma D341 cells in vitro]. AB - OBJECTIVE: To investigate the apoptosis and proliferation effect of matrine on human medulloblastoma cell line D341 in vitro and the effect of the expression of the related caspase 3 and caspase 9 proteins. METHODS: The D341 cells were cultivated successfully in vitro. Then the cells were divided into 5 groups according to the concentration of matrine (0.5 mg/mI group, 1.0 mg/ml group, 1.5 mg/ml group, 2.0 mg/ml group and the control group was 0 mg/ml). All the experiments were repeated three times. The cell morphologic and structure change was observed with the optical microscope and the transmission electron microscope. The proliferation of D341 cell was analyzed using Cell Counting Kit-8 assay. Apoptosis was detected by Annexin V-FITC/PI double staining. The expression of Caspase3 and Caspase9 was detected by Western blot. RESULTS: With the effect of matrine, the proliferation inhibition rate gradually increased with drug concentrations increasing, and there was a significant difference (P < 0.01). The inhibitory effect of matrine on cell proliferation was different with the different treatment time, there was a significant difference between the 24 h to 72 h groups (P < 0.01). The apoptotic rate increased with matrine concentrations increasing. There were significant differences between the group of 0.5 mg/mI or 1.0 mg/mI to the group of 1.5 mg/mI or 2.0 mg/mI (P < 0.05). The apoptotic rate increased with the prolonged treatment time. There were significant differences between the group of 24 h or 48 h to the group of 72 h ( P < 0.05). With the increase of matrine concentration, the expression of Caspase 3 and Caspase 9 increased (P < 0.01). CONCLUSION: Matrine induces the apoptosis, and inhibits the proliferation of human medulloblastoma D341 cells in vitro by up regulation of the expression level of Caspase3, Caspase9. PMID- 27255049 TI - [Effect of nano-SiO2 exposure on spatial learning and memory and LTP of hippocampal dentate gyrus in rats]. AB - OBJECTIVE: To study the effect of nano-SiO2 on spatial learning and memory. METHODS: Twenty-four male rats were randomly divided into 3 groups: control group (C group), low dose group (L group) and high dose group (H group). The rats were intragastrically administrated with nanometer particles at 25 and 100 mg/kg body weight every day for 4 weeks. After exposure, the ability of learning and memory of rats was tested by Morris water maze, and electrophysiological brain stereotactic method was used to test long-tear potentiation (LTP) in dentate gyrus (DG) of the rats. RESULTS: The increase rate of body weight in H group was reduced significantly compared with C group ( P < 0.05). In the space exploration experiment of Morris water maze test, the escape latency of H group was longer than that of C group (P < 0.05). The rats of H group spent less time in finding the target quadrant (P < 0.05) . The rate of LP induction of H group was significantly lower than that of C group (P < 0.05). After high fre quency stimulation (HFS), The changes of amplitude of population spike (PS) of L group and H group were lower than those of C group significantly (P < 0.05, P < 0.01). CONCLUSION: Nano-SiO2may result in impairment of spatial learning and memory ability by reducing the rate of LTP induction and the increase of PS in hippocampus. PMID- 27255050 TI - [Association of CKMM gene A/G polymorphism and athletic performance of uyghurnationality]. AB - OBJECTIVE: Discusses the distributive characters of the Creatine Kinase MM (CKMM) gene A/G Polymorphism in XinjiangUyghur, One hundred and fourtheen athletes and 441 general population of Uyghur were involved in the study. METHODS: Polymerase chain reaction-restriction fragment length polymorphism was used. RESULTS: (1) The CKMM gene A/G frequency in Uyghur general population was(AA, AG and GG) 0.497, 0.392 and 0.111, the result test by Hardy-Weinberg (H-W) equilibrium and x2 = 2.72, P = 0.1, df = 2, indicated that the control group had representative. (2) AA, AG and GG genotype frequency of power-oriented athlete respectively was 0.442,0.302 and 0.256, frequency of GG genotype and G allele was higher than the control group, there were significant differences compared to thecontrol( P < 0.05, df = 2); (3) A/G genotype frequency of Endurance-oriented athletere spectively was 0.571, 0.400 and 0.029, there were nosignificant differences compared to the controls ( P > 0. 05, df = 2). (4) A/G genotype frequency of Uyghur soccer athletes respectively was0.472, 0.361 and 0.167, G allele was higher than the Endurance-oriented athlete and lower than the power-oriented athletes. and no significant differences compared to the controls( P > 0.05, df = 2). CONCLUSION: The results indicate that the CKMM gene GG genotype and G alleleare represented in power-oriented athletes, but don't find A/G polymorphism correlation with endurance and the football sport performance. PMID- 27255051 TI - [Effect of carnitin on skeletal muscle mitochondria H+-K+-ATPase enzyme activity after different intensity exercise intervention in rats]. PMID- 27255052 TI - [The dynamic expression changes of myocardium p-p38MAPK, NF-kappaB and COX-2 in rats after an exhausted exercise]. AB - OBJECTIVE: To observe the dynamic expression changes of p38 mitogen-activated protein kinase (p38MAPK), nucler facter kappa B (NF-kappaB) and cyclooxygenase-2 (COX-2) in myocardial tissue after an exhausted exercise and study the impact of p38MAPK, NF-kappaB and COX-2 on its myocardial damage. METHODS: Sixty Wister male rats were randomly divided into the control group (n = 10) and the exhausted exercise group (n = 50). Then the exhausted exercise group was further divided into 5 subgroups, namely 0 h, 3 h, 6 h, 12 h, 24 h after an exhausted exercise (n = 10). The myocardial injury animal model was set up by using an exhausted swimming exercise and the expression of p-p38MAPK, NF-kappaB and COX-2 were examined by Western blot. RESULTS: Compared with the control group, the expression of p-p38MAPK were increased significantly (P < 0.01) in all the groups and the 3 h group was the highest( P < 0.01); The expression of NF-kappaB were increased significantly (P < 0.05) in all the groups but 0 h P > 0.05) and the 6h group was increased significantly compared with the other groups( P < 0.05); The expression of COX-2 were increased significantly( P < 0.05) in all the groups but 0 h and the 24 h groups was increased significantly compared with the other groups(P < 0.05). CONCLUSION: p38MAPK was activated in an acute exhausted exercise, p-p38MAPK may play an important role in modulating NF-kappaB and COX-2 expression and mediating the exhausted exercise induced myocardial damage. PMID- 27255053 TI - [EEG characteristics of medial prefrontal cortex in rats with morphine dependent place preference under shuttling condition]. AB - OBJECTIVE: To study the correlation between EEG characteristics of medial prefrontal cortex (mPFC) and drug-seeking behavior of rats with morphine dependent place preference under shuttling condition. METHODS: Forty rats were randomly divided into four groups (n = 10): morphine PL group, NS PL group, morphine IL group and NS IL group. After embeding the electrode in prelimbic (PL) or infralimbic (IL) cortex of each group by brain stereotaxic operation, the model of morphine dependent conditioned place preference (CPP) in rats was established. The differences of EEG wave percentage in mPFC were telemetered and analyzed when rats shuttled before and after the model. RESULTS: After the model, the withdrawal symptoms were evident in morphine PL and IL group, and the activity time and distance in white box were increased obviously. Compared with control group, after the model, the EEG in morphine PL group showed that: when the rats shuttled to white box, 8 wave decreased obviously, P wave increased obviously. When the rats shuttled to black box, brain waves showed opposite changes. The EEG in morphine IL group showed that: when the rats shuttled to white box, a wave increased obviously, P and a wave decreased obviously. When the rats shuttled to black box, the brain wave had no significant differences compared with control group. CONCLUSION: The EEG changes are different in PL and IL cortex of morphine CPP rats under shuttling condition, and the EEG changes are also different when rats shuttling to white or black box. There is possibly different mechanism, when different drug-seeking environmental cues caused EEG changes in different regions of mPFC. PMID- 27255054 TI - Investment case concepts in leprosy elimination: A systematic review. AB - INTRODUCTION: Leprosy continues to be a global public health problem, but draws less attention because 'prevalence based elimination' has been misinterpreted as eradication. The ongoing transmission of M. leprae has renewed interest in complete elimination. The aim of our study is to review systematically the literature regarding the elimination of leprosy, and to assess this information on its applicability for defining a Leprosy Elimination Investment Case (LEIC) based on Eradication Investment Case guidelines. METHODOLOGY: A literature search was conducted using the MeSH subheadings and synonyms of leprosy. A total of 1007 articles were considered and 112 were included in the final selection. The search focused on the literature covering leprosy elimination and its public health aspects. The LEIC framework was adapted from an existing "Guide to Preparing an Eradication Investment Case". RESULTS: The LEIC framework provided 11 topics under which information was synthesized from the literature. The fields were categorised under sections: 1) Proposed investment; 2) Rationale for investing; 3) Issues to consider when moving from control to eradication; 4) Management and governance. Scanty quantitative data are available for developing a LEIC, particularly regarding disease burden, and new interventions that could contribute to elimination are not yet applied routinely. DISCUSSION: For monitoring global elimination, it is necessary to measure disease burden comprehensively, and contact centered preventive interventions should be part of a global elimination strategy. The biological and technical feasibility of elimination is not certain and advanced microbiological and operational research is necessary to understand transmission better. The current WHO road map for leprosy elimination is too vague and needs further structuring through a thoroughly prepared LEIC. PMID- 27255055 TI - How to improve early case detection in low endemic areas with pockets of leprosy: a study of newly detected leprosy patients in Guizhou Province, People's Republic of China. AB - Although leprosy in China is controlled at a low endemic level, the number of new cases in Guizhou province has shown no significant decrease over the past 20 years. Guizhou remains the province with the second highest prevalence in China. The authors conducted a study in which the characteristics of newly detected leprosy cases, found between 2008 and 2012 in Guizhou, were analysed. These cases represented people from pocket areas of leprosy in a generally low endemic environment. The purpose of the study was to understand characters of newly detected cases, strong points and weakness of routine detection approaches for improving the effectiveness of early case detection in the future. The analysis considered data that was collected from a 'Leprosy Management Information' report system and also from annual statistical reports of leprosy that reflect the situation throughout the province. 1274 new patients were detected in Guizhou from 2008 to 2012. That number included 58 (4.6%) children (0-14 years old). The average age of patients at diagnosis was 42.6 +/- 16.5 years. The proportion of people with WHO Grade 2 disability (WHO DG2) among new patients was 35.7% and the proportion of people with Grade 1 disability (DG1) constituted 10.1%. The average delay before diagnosis after the onset of symptoms of leprosy was 41.7 +/- 49.8 months. Suspect survey was a major method by which most cases were detected. Trough this method 790 (62.0%) new patients were detected. It was also in this group that the highest proportion of people with WHO DG2 359 of 790 (45.4%) was reported. Self- reporting, diagnosis at a general skin clinic, household contact examination, and spot surveys accounted for 13.0%, 11.8%, 11.5% and 1.7% of other cases detected respectively. It was generally found that cases detected through household contact examinations were earlier cases (delay to diagnosis < 24 months = 70.7%). It was also recorded that fewer of these had WHO DG2 (12.9%). The proportion of men with WHO DG2 was higher than that of females (38.2% compared with 28.8%). The proportion of Han Chinese new cases with WHO DG2 was significantly higher than that of the main minority group (41.5% compared with 29.2%). The proportion of new cases among the main minority group who self reported (50%) was significantly higher than those detected through other detection approaches. Detecting leprosy early in low endemic situations where pockets persist was difficult to achieve. The authors suggest that if more early patients are to be detected earlier, the quality of suspect surveys and household contact examination should be improved. Professional training and supervision might affect that result. Greater emphasis should be given to the role of general skin clinics as surveillance sites and advocacy for new health policy that will enhance the detection leprosy should be sustained. PMID- 27255056 TI - Leprosy in Brazilian counties bordering Paraguay: Mato Grosso do Sul State, 2001 2011. AB - BACKGROUND: In Mato Grosso do Sul state, Brazil, the dry border shared with Paraguay is a territory marked by facilities in the flow of goods, services and people, bringing difficulties for surveillance of communicable diseases. PURPOSE: The purpose of this study is to characterise leprosy epidemiologically in dry border municipalities of Mato Grosso do Sul in Brazil with contiguous urban areas with neighbouring Paraguayan counties, in the period 2001-2011. METHODS: This is an exploratory descriptive investigation that includes the four dry border municipalities of Mato Grosso do Sul (Coronel Sapucaia, Paranhos, Ponta Pora, and Sete Quedas) in Brazil whose urban areas are contiguous with Paraguay. Data comprised the period 2001-2011. RESULTS: The rates of leprosy detection and prevalence oscillated along the study period, increasing in the last 2 years investigated. The detection rate was 3.3/10,000 in 2011, up from 1.7/10,000 in 2009. Prevalence was 5.3/10,000 in 2011, up from 2.5/10,000 in 2009. The Virchowian disease form was predominant in 8 of the 11 years investigated. Most patients were male, with limited formal education (44.2% with less than 4 years of study). CONCLUSION: In the border of Brazil, most (greater than 70%) of the cases detected were classified as multibacillary. The higher coefficient found in Brazilian municipalities was the Virchowian clinical form, which can influence the operational classification in multibacillary. The predominance of the Virchowian clinical form, larger number of patients in rural areas and children under 15 years of age provides new information on the manifestations of the disease in the border territories. The study revealed that municipalities with contiguous cross-border urban areas with Paraguay have unique epidemiological features that need to be addressed by policies focusing leprosy as a public health priority. PMID- 27255057 TI - Children and adolescents' attitude towards having leprosy in a high endemic district of India. PMID- 27255058 TI - The association between neuropathic pain and disability grades in leprosy. AB - OBJECTIVE: To detect neuropathic pain in people who have had leprosy and correlate this association with the WHO Degree of Physical Disability classification (DPD-WHO). PATIENTS AND METHODS: Data were collected from medical records, interviews and physical examinations of patients treated in 2013 in a regional referral service that attends 102 municipals. Clinical and general data, the DPD-WHO classification and the Douleur Neuropathique 4 Questionnaire (DN4) were utilised to determine the profile and to diagnose neuropathic pain. RESULTS: Of 84 treated patients, 37 (44.1%) had leprosy-related pain at the time of the interview. The mean age was 53 years, 51.4% were women; 75.7% had multibacillary disease and 72.9% had some kind of reactional episode. Of the 37 patients with pain, 22 (59.5%) had neuropathic pain and 15 (40.5%) had nociceptive pain. The most frequently reported symptoms related to neuropathic pain, apart from numbness (64.9%), were tingling and touch hypoesthesia (56.8%). Of 22 patients with neuropathic pain, 20 had some physical disability; 14 (63.6%) had Grade I disability, six (27.2%) Grade II, and two (9.3%) Grade zero disability. An association was found between neuropathic pain and degree of disability (P-value < 0.05). CONCLUSION: Of the patients who reported pain related to leprosy, 59.5% had neuropathic pain. The DN4 seems to be suitable for determining the presence of neuropathic pain in leprosy. There is an association between the degree of disability and neuropathic pain, i.e. patients with neuropathic pain tend to have a physical disability too. PMID- 27255059 TI - Correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy. AB - BACKGROUND: In leprosy, sensory function of nerves is evaluated with monofilaments test and the motor function with voluntary muscle test, however electroneuromyography is considered as the gold-standard tool. OBJECTIVES: This study aimed: i) to evaluate the correlation between clinical tests and electroneuromyography for the diagnosis of leprosy neuropathy; and ii) to identify the prevalence of leprosy neuropathy and the most compromised peripheral nerves in leprosy. METHODS: We analysed the data from a nested case-control study that identified 166 patients diagnosed with leprosy neuropathy confirmed by electromyography. This study was designed for an analysis of correlation between the diagnostic tests. RESULTS: The most prevalent type of the neural damage was the sensory and motor multiple mononeuropathy, observed in 62 (37.3%) cases. The highest prevalence was the ulnar nerve in 67 (40.3%) cases. Agreement specified by nerves was moderate, ranging from k = 0.58 in the deep peroneal nerve to k = 0.41 in the posterior tibial nerve). Overall agreement between the clinical tests and electroneuromyography was very poor. Monofilaments test with k = 0.02 (95% CI 0.00-0.12) and voluntary muscle test with 0.16 (95% CI 0.04 to 0.28, P = 0.01). CONCLUSIONS: There is a low to moderate correlation between clinical tests (monofilaments and voluntary muscle tests) and the electroneuromyography examination. The most prevalent type of neural impairment was the sensory and motor multiple mononeuropathy, and the most affected nerve was the ulnar. PMID- 27255060 TI - Prospective analytical study of assessment of off loading by Total Contact Cast in treatment of non healing plantar ulcers in anaesthetic foot. AB - BACKGROUND: Chronic planter ulcer, also known as trophic ulcer, shows no tendency towards healing. It is usually seen in sensory deficient foot. The clinical result of a sensory, motor or autonomic loss of a nerve function is frequently the same--ulceration, although the exact cause may vary. The treatment principle involves dressing and avoiding pressure on the ulcerated site called 'offloading' and patient education for prevention. AIM OF THE STUDY: To determine the outcome of non-healing planter ulcers in an anaesthetic foot treated with offloading, total contact casting (TCC), in terms of rate and duration of healing and percentage of ulcers healed based on improvement of Wagner's grading with respect to the clinical profile of the patient. METHOD: Detailed examination of the patients was done, and neuropathic foot confirmed. Surgical debridement of the ulcer was done to take off all the necrotic tissues, periwound callus, and infected material down to viable tissues. Once the ulcer became clean, a total contact cast was applied with a walking iron for ambulation. TCC was renewed every 2 weeks and rate of healing was assessed. RESULT: 80% of the cases healed within 8 weeks, healing defined by complete re-epithelisation of wound. Average duration of healing of an ulcer was 6.73 +/-1.92 weeks. LIMITATIONS OF THE STUDY: Small sample size and the lack of control subjects for comparison. CONCLUSION: Offloading with total contact casts is believed to be the gold standard method with better and faster healing rates. PMID- 27255061 TI - Association of viable Mycobacterium leprae with Type 1 reaction in leprosy. AB - The working hypothesis is that, viable Mycobacterium leprae (M. leprae) play a crucial role in the precipitation of Type 1 reaction (T1R) in leprosy. MATERIAL AND METHODS: A total of 165 new multibacillary patients were studied. To demonstrate presence of viable M. leprae in reactional lesion (T1R+), three tests were used concurrently viz. growth in the mouse foot pad (MFP), immunohistochemical detection of M. leprae secretory protein Ag85, and 16s rRNA- using in situ RT-PCR. Mirror biopsies and non reactional lesions served as controls (T1R-). FINDINGS: A significantly higher proportion of lesion biopsy homogenates obtained at onset, from T1R(+) cases have shown unequivocal growth in MFP, proving the presence of viable bacteria, as compared to T1R(-) (P < 0.005). In contrast, few Mirror biopsies were positive in both T1R(+) and T1R(-). With respect to Ag85, while the overall positivity was higher in T1R(+) (74%), however the intensity of staining (Grade 2+) was disproportionately higher in T1R(+) BT BB lesions 11/20 (55%). In the rebiopsies obtained during a repeat episode of T1R, Ag 85 as well as 16s rRNA, positivity (62% & 100%) was higher in T1R(+). It is inferred therefore 'viable' bacteria are an essential component in T1R and difference in the quality of bacilli, not the quantity or the ratio of dead to viable play a role in the precipitation of T1R. In conclusion, the findings show that 'metabolically active' M. leprae is a component/prerequisite and the secretory protein Ag 85, might be the trigger for precipitation of T1R. PMID- 27255062 TI - Mutation at codon 442 in the rpoB gene of Mycobacterium leprae does not confer resistance to rifampicin. AB - BACKGROUND: Rifampicin is the major drug in the treatment of leprosy. The rifampicin resistance of Mycobacterium leprae results from a mutation in the rpoB gene, encoding the beta subunit of RNA polymerase. As M. leprae is a non cultivable organism observation of its growth using mouse food-pad (MFP) is the only Gold Standard assay used for confirmation of "in-vivo" drug resistance. OBJECTIVE: Any mutation at molecular level has to be verified by MFP assay for final confirmation of drug resistance in leprosy. MATERIAL AND METHODS: In the present study, M. leprae strains showing a mutation only at codon 442 Gln-His and along with mutation either at codon 424 Val-Gly or at 438 Gln-Val within the Rifampicin Resistance Determining Region (RRDR) confirmed by DNA sequencing and by high resolution melting (HRM) analysis were subjected for its growth in MFP. RESULT AND CONCLUSION: The M. leprae strain having the new mutation at codon 442 Gln-His was found to be sensitive to all the three drugs and strains having additional mutations at 424 Val-Gly and 438 Gln-Val were conferring resistance with Multi drug therapy (MDT) in MFP. These results indicate that MFP is the gold standard method for confirming the mutations detected by molecular techniques. PMID- 27255063 TI - Autochthonous borderline tuberculoid leprosy in a man from Florida. AB - Leprosy (Hansen's disease) is a chronic contagious granulomatous disease principally affecting the skin and peripheral nervous system, caused by Mycobacterium leprae. In this report, we present a case of autochthonous leprosy in a man from Florida as the first human case reported from this region. Authors believe dermatologists need to be aware of the possibility of autochthonous transmission of leprosy in the Eastern-Southern United States, and should consider leprosy in any patient with atypical skin lesions, even when a history of contact with armadillo is missing. PMID- 27255064 TI - The story of a deformed leprous foot. AB - Eccrine syringofibroadenoma (ESFA) is a rare adnexal tumour of eccrine ductal proliferation. A 50 year old treated case of leprosy presented with a chronic non healing ulcer of 5 years duration on the deformity laden right foot. Multiple verrucous papules and plaques were seen surrounding the ulcer which showed histopathological findings consistent with ESFA. Although ESFA constitutes a rare association with leprosy, considering the load of treated cases in our country and elsewhere, it may represent an under-reported entity which requires more attention in the post elimination era. PMID- 27255065 TI - Tuberculosis and leprosy infections in the Marshallese population of Arkansas, USA. AB - The cross-immunity between tuberculosis and leprosy is unknown. The aim of this pilot study was to evaluate the occurrence of Mycobacterium tuberculosis and M. leprae infection in Marshallese adult volunteers in Springdale, Arkansas, U.S.A., a population that experiences high rates of leprosy and tuberculosis. We used immunodiagnostic testing for tuberculosis and leprosy infection and found significant prevalence of latent tuberculosis infection (19.0%), and asymptomatic Mycobacterium leprae infection (22.2%). We found a negative association between presence of antibodies to Mycobacterium leprae and a positive interferon-gamma release assay for Mycobacterium tuberculosis infection, prevalence odds ratio = 0.1 (95% CI = 0.0, 0.9). Although these findings require confirmation on a larger scale, they are supportive of the existence of cross-immunity. PMID- 27255066 TI - Validation of the Leprosy Type 1 Reaction Severity Scale in Ethiopia. PMID- 27255067 TI - Management of chronic neuritis with a combination regimen of lower doses prednisolone and methotrexate: a brief report. AB - INTRODUCTION: Recommended fixed duration prednisolone regimen was not found effective in the treatment of chronic neuritis. Alternate effective treatment was being sought to reduce the deformity in the field of leprosy. OBJECTIVE: We wished to see whether a prolonged course of prednisolone and methotrexate could be of any help for them. METHODOLOGY: In 2012-2014, an open pilot clinical study was undertaken where three chronic neuritic patients were treated with lower doses prednisolone and methotrexate for 12 months and a follow up period was delivered for 12 months. The study was undertaken in one of the outdoor clinics of the university. RESULTS: Complete and permanent remission of neuritis was achieved with appreciable functional recovery. Few mild self-limiting side effects from prednisolone were observed and there was no side-effects from methotrexate. CONCLUSION: Prolonged course of prednisolone and methotrexate was found safe and effective in treating chronic neuritis. PMID- 27255068 TI - Bone marrow evaluation in leprosy: clinical implications. PMID- 27255069 TI - Cultural practice and beliefs hampering the treatment of leprosy--an area of concern. PMID- 27255070 TI - Dr. H. Srinivasan (1929-2015). PMID- 27255071 TI - Thomas Herald Rea, MD (1929-2016). PMID- 27255072 TI - Symposium on emerging needs in leprosy research in the post elimination era: The Leprosy Mission Trust India. PMID- 27255073 TI - Metabolic Risk Profile and Cancer in Korean Men and Women. AB - OBJECTIVES: Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. METHODS: We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. RESULTS: A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. CONCLUSIONS: The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women. PMID- 27255074 TI - Blood Triglycerides Levels and Dietary Carbohydrate Indices in Healthy Koreans. AB - OBJECTIVES: Previous studies have obtained conflicting findings regarding possible associations between indices measuring carbohydrate intake and dyslipidemia, which is an established risk factor of coronary heart disease. In the present study, we examined cross-sectional associations between carbohydrate indices, including the dietary glycemic index (GI), glycemic load (GL), total amount of carbohydrates, and the percentage of energy from carbohydrates, and a range of blood lipid parameters. METHODS: This study included 1530 participants (554 men and 976 women) from 246 families within the Healthy Twin Study. We analyzed the associations using a generalized linear mixed model to control for familial relationships. RESULTS: Levels of the Apo B were inversely associated with dietary GI, GL, and the amount of carbohydrate intake for men, but these relationships were not significant when fat-adjusted values of the carbohydrate indices were used. Triglyceride levels were positively associated with dietary GI and GL in women, and this pattern was more notable in overweight participants (body mass index [BMI] >=25 kg/m(2)). However, total, low-density lipoprotein and high-density lipoprotein cholesterol levels were not significantly related with carbohydrate intake overall. CONCLUSIONS: Of the blood lipid parameters we investigated, only triglyceride levels were positively related with dietary carbohydrate indices among women participants in the Healthy Twin Study, with an interactive role observed for BMI. However, these associations were not observed in men, suggesting that the association between blood lipid levels and carbohydrate intake depends on the type of lipid, specific carbohydrate indices, gender, and BMI. PMID- 27255075 TI - Risk Factors for Preterm Birth and Low Birth Weight Among Pregnant Indian Women: A Hospital-based Prospective Study. AB - OBJECTIVES: The present study was undertaken to study the maternal risk factors for preterm birth (PTB) and low birth weight (LBW) with a special emphasis on assessing the proportions of maternal genitourinary and periodontal infections among Indian women and their association with adverse pregnancy outcomes. METHODS: A hospital-based prospective study comprising 790 pregnant women visiting the obstetrics clinic for a routine antenatal check-up was undertaken. Once recruited, all study participants underwent clinical and microbiological investigations for genitourinary infections followed by a dental check-up for the presence of periodontitis. The study participants were followed up until their delivery to record the pregnancy outcomes. Infectious and non-infectious risk factors for PTB and LBW were assessed using univariate and multivariate Cox regression analysis. Independent risk factors for PTB and LBW were reported in terms of adjusted relative risk (ARR) with the 95% confidence interval (CI). RESULTS: Rates of PTB and LBW in the study population were 7.6% and 11.4%, respectively. Previous preterm delivery (ARR, 5.37; 95% CI, 1.5 to 19.1), periodontitis (ARR, 2.39; 95% CI, 1.1 to 4.9), Oligohydramnios (ARR, 5.23; 95% CI, 2.4 to 11.5), presence of Nugent's intermediate vaginal flora (ARR, 2.75; 95% CI, 1.4 to 5.1), gestational diabetes mellitus (ARR, 2.91; 95% CI, 1.0 to 8.3), and maternal height <1.50 m (ARR, 2.21; 95% CI, 1.1 to 4.1) were risk factors for PTB, while periodontitis (ARR, 3.38; 95% CI, 1.6 to 6.9), gestational hypertension (ARR, 3.70; 95% CI, 1.3 to 10.8), maternal height <1.50 m (ARR, 2.66; 95% CI, 1.3 to 5.1) and genital infection during later stages of pregnancy (ARR, 2.79; 95% CI, 1.2 to 6.1) were independent risk factors for LBW. CONCLUSIONS: Our study findings underscore the need to consider screening for potential genitourinary and periodontal infections during routine antenatal care in developing countries. PMID- 27255076 TI - Depressive Symptoms on the Geriatric Depression Scale and Suicide Deaths in Older Middle-aged Men: A Prospective Cohort Study. AB - OBJECTIVES: Prospective evaluations of the associations between depressive symptoms and suicide deaths have been mainly performed in high-risk populations, such as individuals with psychiatric disorders or histories of self-harm. The purpose of this study was to prospectively examine whether more severe depressive symptoms assessed using the Geriatric Depression Scale (GDS) were associated with a greater risk of death from suicide in a general-risk population. METHODS: A total of 113 478 men from the Korean Veterans Health Study (mean age, 58.9 years) who participated in a postal survey in 2004 were followed up for suicide mortality until 2010. RESULTS: Over 6.4 years of follow-up, 400 men died by suicide (56.7 deaths per 100 000 person-years). More severe depressive symptoms were associated with greater risk of suicide death (p for trend <0.001). The unadjusted hazard ratios (HRs) in comparison to the absence of depression were 2.18 for mild depression, 2.13 for moderate depression, 3.33 for severe depression, and 3.67 for extreme depression. After adjusting for potential confounders, men with a potential depressive disorder had an approximate 90% higher mortality from suicide (adjusted HR, 1.92; 95% confidence interval [CI], 1.38 to 2.68; p<0.001) than men without depression. Each five-point increase in the GDS score was associated with a higher risk of death by suicide (adjusted HR, 1.22; p<0.001). The value of the area under the receiver operating characteristics curve of GDS scores for suicide deaths was 0.61 (95% CI, 0.58 to 0.64). CONCLUSIONS: Depressive symptoms assessed using the GDS were found to be a strong independent predictor of future suicide. However, the estimate of relative risk was weaker than would be expected based on retrospective psychological autopsy studies. PMID- 27255077 TI - SUSHI: an exquisite recipe for fully documented, reproducible and reusable NGS data analysis. AB - BACKGROUND: Next generation sequencing (NGS) produces massive datasets consisting of billions of reads and up to thousands of samples. Subsequent bioinformatic analysis is typically done with the help of open source tools, where each application performs a single step towards the final result. This situation leaves the bioinformaticians with the tasks to combine the tools, manage the data files and meta-information, document the analysis, and ensure reproducibility. RESULTS: We present SUSHI, an agile data analysis framework that relieves bioinformaticians from the administrative challenges of their data analysis. SUSHI lets users build reproducible data analysis workflows from individual applications and manages the input data, the parameters, meta-information with user-driven semantics, and the job scripts. As distinguishing features, SUSHI provides an expert command line interface as well as a convenient web interface to run bioinformatics tools. SUSHI datasets are self-contained and self documented on the file system. This makes them fully reproducible and ready to be shared. With the associated meta-information being formatted as plain text tables, the datasets can be readily further analyzed and interpreted outside SUSHI. CONCLUSION: SUSHI provides an exquisite recipe for analysing NGS data. By following the SUSHI recipe, SUSHI makes data analysis straightforward and takes care of documentation and administration tasks. Thus, the user can fully dedicate his time to the analysis itself. SUSHI is suitable for use by bioinformaticians as well as life science researchers. It is targeted for, but by no means constrained to, NGS data analysis. Our SUSHI instance is in productive use and has served as data analysis interface for more than 1000 data analysis projects. SUSHI source code as well as a demo server are freely available. PMID- 27255078 TI - Articular cartilage generation applying PEG-LA-DM/PEGDM copolymer hydrogels. AB - BACKGROUND: Injuries to the human native cartilage tissue are particularly problematic because cartilage has little to no ability to heal or regenerate itself. Employing a tissue engineering strategy that combines suitable cell sources and biomimetic hydrogels could be a promising alternative to achieve cartilage regeneration. However, the weak mechanical properties may be the major drawback to use fully degradable hydrogels. Besides, most of the fully degradable hydrogels degrade too fast to permit enough extracellular matrix (ECM) production for neocartilage formation. In this study, we demonstrated the feasibility of neocartilage regeneration using swine articular chondrocytes photoencapsualted into poly (ethylene glycol) dimethacrylate (PEGDM) copolymer hydrogels composed of different degradation profiles: degradable (PEG-LA-DM) and nondegradable (PEGDM) macromers in molar ratios of 50/50, 60/40, 70/30, 80/20, and 90/10. METHODS: Articular chondrocytes were isolated enzymatically from juvenile Yorkshire swine cartilage. 6 * 10(7) cells cells were added to each milliliter of macromer/photoinitiator (I2959) solution. Nonpolymerized gel containing the cells (100 MUL) was placed in cylindrical molds (4.5 mm diameter * 6.5 mm in height). The macromer/photoinitiator/chondrocyte solutions were polymerized using ultraviolet (365 nm) light at 10 mW/cm(2) for 10 mins. Also, an articular cartilaginous ring model was used to examine the capacity of the engineered cartilage to integrate with native cartilage. Samples in the pilot study were collected at 6 weeks. Samples in the long-term experimental groups (60/40 and 70/30) were implanted into nude mice subcutaneously and harvested at 6, 12 and 18 weeks. Additionally, cylindrical constructs that were not implanted used as time zero controls. All of the harvested specimens were examined grossly and analyzed histologically and biochemically. RESULTS: Histologically, the neocartilage formed in the photochemically crosslinked gels resembled native articular cartilage with chondrocytes in lacunae and surrounded by new ECM. Increases in total DNA, glycosaminoglycan, and hydroxyproline were observed over the time periods studied. The neocartilage integrated with existing native cartilage. CONCLUSIONS: Articular cartilage generation was achieved using swine articular chondrocytes photoencapsulated in copolymer PEGDM hydrogels, and the neocartilage tissue had the ability to integrate with existing adjacent native cartilage. PMID- 27255080 TI - Effectiveness of a medication-adherence tool: study protocol for a randomized controlled trial. AB - BACKGROUND: Research shows that more than half of the people taking medication for a chronic condition are non-adherent. Nonadherence hinders disease control with a burden on patient quality of life and healthcare systems. We developed a tool that provides insight into nonadherence risks and barriers for medication adherence including an intervention strategy to overcome those barriers. This study aims to assess the effectiveness of using this adherence tool in starters with cardiovascular or oral blood glucose-lowering medication to improve medication-adherence. METHODS/DESIGN: In a cluster-randomized controlled trial 25 pharmacies in the Netherlands will be randomized to the intervention or control arm. Patients registered in a general practice participating in a collaborative can be included when they start cardiovascular or oral blood glucose-lowering medication prescribed by their general practitioner. Participants complete an assessment consisting of measuring nonadherence risk and potential barriers to adherence. For patients with an increased nonadherence risk, a graphic barrier profile is created, showing to what extent eight cognitive, emotional, or practical barriers are present. All patients will fill in the medication adherence assessment twice: between 1 and 2 weeks after the start of the medication and after 8 months. The intervention strategy consists of discussing this barrier profile to overcome barriers. Pharmacists and assistants of the intervention pharmacies are trained in discussing the profile and to offer a tailored intervention to overcome barriers. In the control arm, patients receive care as usual. The primary outcome is medication-adherence of patients with a high risk of nonadherence at 8 months follow-up. Secondary outcomes include the difference in the percentage of patients with an increased nonadherence risk between intervention and control group after 8 months, the predictive values of the baseline questionnaire in the control group in relation to medication adherence after 8 months, medication-adherence after 1 year follow-up, and barriers and facilitators in the implementation of the tool. DISCUSSION: This manuscript presents the protocol for a cluster-randomized clinical trial on the use of an adherence tool to improve medication-adherence. This study will provide insight into the effectiveness of the tool in starters with cardiovascular or oral blood glucose-lowering medication in improvement of medication-adherence. TRIAL REGISTRATION: The Netherlands National Trial Register, NTR5186 . Registered on 18 May 2015. PMID- 27255079 TI - The Probiotics in Pregnancy Study (PiP Study): rationale and design of a double blind randomised controlled trial to improve maternal health during pregnancy and prevent infant eczema and allergy. AB - BACKGROUND: Worldwide there is increasing interest in the manipulation of human gut microbiota by the use of probiotic supplements to modify or prevent a range of communicable and non-communicable diseases. Probiotic interventions administered during pregnancy and breastfeeding offer a unique opportunity to influence a range of important maternal and infant outcomes. The aim of the Probiotics in Pregnancy Study (PiP Study) is to assess if supplementation by the probiotic Lactobacillus rhamnosus HN001 administered to women from early pregnancy and while breastfeeding can reduce the rates of infant eczema and atopic sensitisation at 1 year, and maternal gestational diabetes mellitus, bacterial vaginosis and Group B Streptococcal vaginal colonisation before birth, and depression and anxiety postpartum. METHODS/DESIGN: The PiP Study is a two centre, randomised, double-blind placebo-controlled trial in Wellington and Auckland, New Zealand. Four hundred pregnant women expecting infants at high risk of allergic disease will be enrolled in the study at 14-16 weeks gestation and randomised to receive either Lactobacillus rhamnosus HN001 (6 * 10(9) colony forming units per day (cfu/day)) or placebo until delivery and then continuing until 6 months post-partum, if breastfeeding. Primary infant outcomes are the development and severity of eczema and atopic sensitisation in the first year of life. Secondary outcomes are diagnosis of maternal gestational diabetes mellitus, presence of bacterial vaginosis and vaginal carriage of Group B Streptococcus (at 35-37 weeks gestation). Other outcome measures include maternal weight gain, maternal postpartum depression and anxiety, infant birth weight, preterm birth, and rate of caesarean sections. A range of samples including maternal and infant faecal samples, maternal blood samples, cord blood and infant cord tissue samples, breast milk, infant skin swabs and infant buccal swabs will be collected for the investigation of the mechanisms of probiotic action. DISCUSSION: The study will investigate if mother-only supplementation with Lactobacillus rhamnosus HN001 in pregnancy and while breastfeeding can reduce rates of eczema and atopic sensitisation in infants by 1 year, and reduce maternal rates of gestational diabetes mellitus, bacterial vaginosis, vaginal carriage of Group B Streptococcus before birth and maternal depression and anxiety postpartum. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registration: ACTRN12612000196842. Date Registered: 15/02/12. PMID- 27255081 TI - Septochoanal polyp with osseous metaplasia: a case report. AB - BACKGROUND: Polyps originating from the posterior septum with choanal extension, also known as "septochoanal polyps," are uncommon, and septochoanal polyps with central calcification are extremely rare. We report the second case of septochoanal polyps with central calcification in the English literature. CASE PRESENTATION: A 55-year-old Thai woman presented with a progressive left-side nasal obstruction. An examination of her nose revealed an irregular lobulated mass, yellow in color, with a smooth surface that arose from her posterior nasal septum and extended down to her nasopharynx. Computed tomography revealed a large choanal mass with a central ossified structure. A punch biopsy was performed and microscopic examination showed an inflammatory polyp. The mass was removed using an endoscopic surgery technique, and the histology of this lesion confirmed a typical presentation of choanal polyps. CONCLUSIONS: Although septochoanal polyps with osseous metaplasia are known to be very rare, physicians should be aware of them and include them in the differential diagnosis of choanal mass with central calcification lesions. PMID- 27255082 TI - The global network antenatal corticosteroids trial: impact on stillbirth. AB - BACKGROUND: Antenatal corticosteroids are commonly used to reduce neonatal mortality, but most research to date has been in high-resource settings and few studies have evaluated its impact on stillbirth. In the Antenatal Corticosteroids Trial (ACT), a multi-country trial to assess impact of a multi-faceted intervention including antenatal corticosteroids to reduce neonatal mortality associated with preterm birth, we found an overall increase in 28-day neonatal mortality and stillbirth associated with the intervention. METHODS: The ACT was a cluster-randomized trial conducted in 102 clusters across 7 research sites in 6 countries (India [2 sites], Pakistan, Zambia, Kenya, Guatemala and Argentina), comparing an intervention to train birth attendants at all levels of the health system to identify women at risk of preterm birth, administer corticosteroids and refer women at risk. Because of inadequate gestational age dating, the <5(th) percentile birth weight was used as a proxy for preterm birth. A pre-specified secondary outcome of the trial was stillbirth. RESULTS: After adjusting for the pre-trial imbalance in stillbirth rates, the ACT intervention was associated with a non-significant increased risk of stillbirth (aRR 1.08, 95 % CI, 0.99-1.17, p 0.073). Additionally, the stillbirth rate was higher in the term births (1.20 95 % CI 1.06-1.37, 0.004) and among those with signs of maceration (RR 1.18 (1.04 1.35), p = 0.013) in the intervention vs. control clusters. Differences in obstetric care favored the control clusters and maternal infection was likely more common in the intervention clusters. CONCLUSIONS: In this pragmatic trial, limited data were available to identify the causes of the increase in stillbirths in the intervention clusters. A higher rate of stillbirth in the intervention clusters prior to the trial, differences in obstetric care and an increase in maternal infection are potential explanations for the observed increase in stillbirths in the intervention clusters during the trial. TRIAL REGISTRATION: clinicaltrials.gov (NCT01084096). PMID- 27255084 TI - The status of the Notes in the International Code of Nomenclature of Prokaryotes: proposal to emend General Consideration 6. AB - The International Code of Nomenclature of Prokaryotes contains 48 Notes to the General Considerations, the Principles, the Rules and the Recommendations. However, the formal status of these Notes is not defined in the Code. Therefore, we here propose an emendation of General Consideration 6 stating that the Notes are intended to clarify the preceding text and are an integral part of that text. PMID- 27255083 TI - Role of the ion channel, transient receptor potential cation channel subfamily V member 1 (TRPV1), in allergic asthma. AB - BACKGROUND: Asthma prevalence has increased world-wide especially in children; thus there is a need to develop new therapies that are safe and effective especially for patients with severe/refractory asthma. CD4(+) T cells are thought to play a central role in disease pathogenesis and associated symptoms. Recently, TRPV1 has been demonstrated to regulate the activation and inflammatory properties of CD4(+) cells. The aim of these experiments was to demonstrate the importance of CD4(+) T cells and the role of TRPV1 in an asthma model using a clinically ready TRPV1 inhibitor (XEN-D0501) and genetically modified (GM) animals. METHODS: Mice (wild type, CD4 (-/-) or TRPV1 (-/-)) and rats were sensitised with antigen (HDM or OVA) and subsequently topically challenged with the same antigen. Key features associated with an allergic asthma type phenotype were measured: lung function (airway hyperreactivity [AHR] and late asthmatic response [LAR]), allergic status (IgE levels) and airway inflammation. RESULTS: CD4(+) T cells play a central role in both disease model systems with all the asthma-like features attenuated. Targeting TRPV1 using either GM mice or a pharmacological inhibitor tended to decrease IgE levels, airway inflammation and lung function changes. CONCLUSION: Our data suggests the involvement of TRPV1 in allergic asthma and thus we feel this target merits further investigation. PMID- 27255085 TI - Egyptian prosecutors investigate the death of a girl during female genital mutilation. PMID- 27255087 TI - Clinical Management of ADHD in a Family Medicine Residency Program: Comparison with AAP Guidelines. AB - OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder. Research has shown that even with the growing incidence of children diagnosed as having ADHD, physicians may find providing optimal care to these patients challenging. Our objective was to contrast existing clinical management of ADHD in a family medicine setting with published American Academy of Pediatrics guidelines and review the literature pertinent to differences. METHODS: A report was generated for all visits with "ADHD" or "ADD" (attention deficit disorder) as a current or past medical problem that had been addressed at the family medicine clinic from July 2012 to June 2014. A total of 60 pediatric patients were identified. A retrospective chart review of clinical practice and management patterns for these patients was completed using a standardized data collection form based on the 2011 ADHD treatment guidelines set by the American Academy of Pediatrics. RESULTS: Fifty-seven (95%) patients had documentation of at least one core symptom of ADHD, and 27 (45%) patients had documentation of these symptoms in more than one setting (clinic/school/home). Only 30 (50%) patients were assessed at the initial ADHD visit for coexisting conditions. Coexisting conditions were found to be present in 20 (33.3%) patients. Of these 20 patients, coexisting conditions were not addressed during the visit in 12 (60%) patients before drug therapy for ADHD was initially prescribed. Behavioral therapy was initiated as first-line monotherapy in one of the nine preschool-age patients (4-5 years old). Fifty-two (86.7%) patients received a preferred initial medication as identified by guidelines, and 41 (78.8%) of those patients received an appropriate initial dose. Fifty-one (85%) patients were assessed for improvement of symptoms, and 39 (65%) were assessed for adverse events. Of 62 documented medication adjustments, 54 (87.1%) adjustments coincided with current practice guidelines. Sixteen (26.7%) patients were referred to mental health specialists. CONCLUSIONS: This retrospective review identified areas of strength and weakness for attending physicians and medical residents in the diagnosis, evaluation, and treatment of children with ADHD. A significant need was identified for more physician-focused education on the evaluation of coexisting conditions and long-term management associated with ADHD therapy. Further training in the initiation of behavioral therapy as a first-line treatment above drug therapy and proper medication selection in children aged 4 to 5 years also are recommended. PMID- 27255088 TI - Scorpion Envenomation in Pregnancy. AB - Scorpion envenomation affects more than 1 million people every year and represents an important public health problem worldwide. The effects of envenomation range from localized pain and paresthesias to overactivation of the sympathetic nervous system, leading to neurotoxicity and even death. Of the individuals affected by scorpion envenomation, certain populations, such as young children and older adults, are at high risk for severe disease. Substantial literature exists on the management of envenomation in children; however, scant literature exists that addresses the same phenomenon in pregnant women. This review serves to identify the effects of scorpion envenomation on pregnant women and the treatment options available to them. After thorough review of the treatment modalities that are used to treat scorpion envenomation, we developed a treatment algorithm that may help guide the management of pregnant women who present with scorpion envenomation. PMID- 27255086 TI - RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer programs. AB - The mechanisms of tumor cell dissemination and the contribution of membrane trafficking in this process are poorly understood. Through a functional siRNA screening of human RAB GTPases, we found that RAB2A, a protein essential for ER to-Golgi transport, is critical in promoting proteolytic activity and 3D invasiveness of breast cancer (BC) cell lines. Remarkably, RAB2A is amplified and elevated in human BC and is a powerful and independent predictor of disease recurrence in BC patients. Mechanistically, RAB2A acts at two independent trafficking steps. Firstly, by interacting with VPS39, a key component of the late endosomal HOPS complex, it controls post-endocytic trafficking of membrane bound MT1-MMP, an essential metalloprotease for matrix remodeling and invasion. Secondly, it further regulates Golgi transport of E-cadherin, ultimately controlling junctional stability, cell compaction, and tumor invasiveness. Thus, RAB2A is a novel trafficking determinant essential for regulation of a mesenchymal invasive program of BC dissemination. PMID- 27255089 TI - Making of a Successful Early Mobilization Program for a Medical Intensive Care Unit. AB - OBJECTIVES: To provide a guideline for intensive care unit (ICU) early mobilization program development and implementation and to describe the patient characteristics and endpoints for those who participated in our hospital's early mobilization program. METHODS: An ICU early mobilization program was developed with five guiding principles: analgesia/sedation optimization, sedation minimization, protocol of progressive mobility, physical therapy and occupational therapy recruitment, and nursing education. This program began in April 2014, and the initial 32 patients who ambulated while receiving mechanical ventilation were retrospectively assessed and their characteristics described. RESULTS: After program implementation, more than 50 mechanically ventilated patients ambulated in the first year following early mobilization initiation. Patients with an FiO2 as high as 1.0 and on nonconventional modes of mechanical ventilation successfully ambulated without adverse events. The mean ambulation distance was 102 +/- 152 f. and usually required three ICU staff members with 5 to 10 minutes of preparation before ambulation. After implementation, a retrospective analysis revealed a decrease in the average length of ICU stay, from 4.8 to 4.1 days. CONCLUSIONS: Addressing analgesia and sedation practices, along with instituting a progressive mobility protocol and recruiting physical and occupational therapy, may serve as a guide to the creation of a successful early mobilization program. This study provides additional supportive evidence that early mobilization in the ICU is safe and effective. PMID- 27255090 TI - Cardiovascular Health Status in Baby Boomers with Diabetes Mellitus. AB - OBJECTIVES: The objective of this study was to assess the cardiovascular health status of baby boomers with diabetes mellitus (DM) in comparison to the same-age population with DM 10 years previously. METHODS: The study was conducted in baby boomers with DM using data from the National Health and Nutrition Examination Survey (NHANES) 2009-2012 compared with NHANES 1999-2002. Cardiovascular health metrics were derived from the American Heart Association's Life's Simple 7. The primary outcome was the comparison of the proportion of individuals with each characteristic, including healthy diet, healthy weight, not smoking, exercising regularly, and maintaining an optimal level of glycated hemoglobin (HbA1C), cholesterol, and blood pressure. RESULTS: Current baby boomers with DM (NHANES 2009-2012) had more obesity (70.9% vs 58.8%; P = 0.009) and a lower proportion of ideal physical activity (20.9% vs 31.7%; P = 0.01) than people of the same age 10 years ago; fewer than 1% adhere to an ideal healthy diet. Current baby boomers more often had ideal cholesterol (59.4% vs 47.2; P = 0.01) and reached an ideal HbA1C (51.0% vs 43.4%; P = 0.047). Blood pressure control, adherence to ideal diet, and smoking rates were not significantly different from 10 years ago. In logistic regression analyses controlling for likely confounders, baby boomers persisted in having more obesity and exercising less often, and reaching an ideal cholesterol level more often (P < 0.01). CONCLUSIONS: Although improving in cholesterol and HbA1C, baby boomers demonstrated worsening in several key cardiovascular health indicators, particularly obesity and physical activity. PMID- 27255091 TI - Positive Predictive Value of a Single Assessment of Estimated GFR in the Diagnosis of Chronic Kidney Disease. AB - OBJECTIVES: The positive predictive value (PPV) of a single assessment of estimated glomerular filtration rate (eGFR) in the diagnosis of chronic kidney disease (CKD) is not known. Our objective was to determine the PPV of a single assessment of eGFR among adults with at least one eGFR <60 mL/min in their lifetime, using the Distributed Area Research and Therapeutics Network CKD natural history dataset. METHODS: In all, 47,104 adults who were cared for by 113 practices in the United States were included. Proportions of patients in eGFR categories at baseline were calculated using the following categories: <15 mL/min, 15 to 29.99 mL/min, 30 to 44.99 mL/min, and 45 to 59.99 mL/min. Comparisons were then made between the baseline and the endpoint to identify patients who had a follow-up eGFR that remained at <60 mL/min. The proportions of patients in each eGFR category were compared baseline to endpoint using cross tabulations. To test the proposed cutpoint, the proportions of patients who had an eGFR that remained at <60 mL/min were measured, using the cutpoints that included the highest cumulative proportion of patients. The sensitivity and specificity of that cutpoint were calculated. RESULTS: A cutpoint of <45 mL/min was identified, yielding a PPV of 93% with a sensitivity of 28% and a specificity of 94%. CONCLUSIONS: A valid cutpoint to screen for CKD was identified. This cutpoint may prove important to early screening for CKD while reducing the burden on the healthcare system and patients suspected of having CKD. PMID- 27255093 TI - Commentary on "Therapeutic Error Calls Among Older Adults Reported to a Regional Poison Control Center in Alabama". PMID- 27255092 TI - Therapeutic Error Calls Among Older Adults Reported to a Regional Poison Control Center in Alabama. AB - OBJECTIVES: Although Americans aged 65 years and older account for only 13.0% of the population, they consume one-third of all prescription medications each year. Increased life expectancy, age-related deterioration in health, and polypharmacy lead to a significant risk of potential medication errors. National Poison Data System studies have evaluated the older adult population and their interaction with poison centers; however, descriptive studies using regional poison center data to evaluate older adult-related medication errors, specifically in Alabama, have not been conducted. Our study assessed therapeutic errors in patients aged 65 years and older to evaluate the need for potential interventions by pharmacists and preventive education to reduce errors reported to the Regional Poison Control Center (RPCC) at Children's of Alabama. METHODS: A four-year retrospective analysis was conducted by gathering call-specific data from the RPCC toxiCALL database. Calls were included if they were made to the RPCC between January 1, 2010 and December 31, 2013, involved patients aged 65 years and older, and were coded as unintentional therapeutic errors. Analysis of call data was conducted using the Centers for Disease Control and Prevention's EpiInfo version 7.0.9.7. RESULTS: A total of 1699 calls were evaluated for patient demographics (sex, age), call data (month, year, shift, caller site), reason for therapeutic error, clinical effects, medical outcome, management site, and reported substance details. Nearly 40.0% of the therapeutic errors were caused by patients taking or being given the same medication twice. Five of the 15 reasons for therapeutic errors accounted for nearly 82.0% of all calls reported. The reasons included taking or being given the same medication twice (37.3%), taking or being given the wrong medication (14.6%), using an incorrect dosing route (13.1%), other incorrect dosing errors (9.9%), and taking doses too close together (7.5%). The top individual substance involved in a therapeutic error was reported verbatim by callers as Spiriva inhalation capsules (10.5%). CONCLUSIONS: Therapeutic error calls represent a significant and increasing proportion of calls made by older adults to the RPCC. The frequent interactions between healthcare providers and patients create opportunities to prospectively prevent medication problems in older adult patients. Healthcare providers, specifically pharmacists, should encourage clients to always read the label on medications and should counsel patients carefully when dispensing a product that is not an oral preparation. In addition, although national drug take-back days are conducted biennially, patients should be encouraged to dispose of old medications and expired over-the counter medications. The RPCC toll-free telephone number (800-222-1222) may be displayed to educate patients on its 24-hour/day availability. Current data will be used to implement programs for pharmacist interventions and to create appropriate educational material. PMID- 27255094 TI - Predictor of 90-Day Readmission Rate for Hepatic Encephalopathy. AB - OBJECTIVES: The purpose of our study was to identify clinical parameters associated with readmissions within 90 days in patients with hepatic encephalopathy (HE). METHODS: We reviewed electronic medical records of patients admitted between January 1, 2010 and September 30, 2013 at University Medical Center, Lubbock, Texas. Inclusion criteria were admission to the hospital with diagnosis of HE in patients older than 18 years. We compared the patients with readmission within 90 days with patients with no readmission using routine clinical data. RESULTS: A total of 140 admissions met inclusion criteria; 35% were white, 59.3% were Hispanic, and their mean age was 55.6 +/- 10.5 years. The median admission Model for End-Stage Liver Disease score was 15.5 (4-38). Univariate analysis demonstrated that a history of diabetes mellitus, a history of hypertension, prior transjugular intrahepatic portosystemic shunt placement, a history of prior HE, and the use of lactulose posthospitalization were associated with increased readmission rates and the presence of gastrointestinal bleeding was associated with decreased readmission rates (P < 0.05 for each factor). Multivariate logistic regression demonstrated that history of hypertension (P = 0.02) predicted an increased readmission rate. CONCLUSIONS: Our study demonstrates that hypertension increased the risk of readmission in patients with HE. More intensive interventions in these patients may decrease readmission rates and improve outcomes. PMID- 27255095 TI - Commentary on "Predictor of 90-Day Readmission Rate for Hepatic Encephalopathy". PMID- 27255096 TI - PPACA and Low-Income People Living with HIV: 2014 Qualified Health Plan Enrollment in a Medicaid Nonexpansion State. AB - People living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) often are uninsured or underinsured, and they may benefit from the Patient Protection and Affordable Care Act (PL 111-148) and its improved access to medical care. Safety net programs, such as AIDS Drug Assistance Programs (ADAP) funded through the Ryan White HIV/AIDS Program, which serve low-income people living with HIV, are incorporating Patient Protection and Affordable Care Act Marketplace-qualified health plans (QHPs) and helping to fund patients' participation. This changing landscape differs from state to state, and one main element contributing to the differing situations is whether a state elected to expand Medicaid. This review examines QHP enrollment of ADAP clients in Virginia, a Medicaid nonexpansion state, and explores some issues that affect people living with HIV in other Medicaid nonexpansion states. Virginia is a leader in the shift of ADAP healthcare delivery from direct medication provision to purchasing QHPs. Virginia ADAP clients accounted for approximately 2% of ADAP clients nationally, but they represent 17% of ADAP clients enrolled in QHPs nationwide. Ensuring good HIV care of the ADAP population is important to each patient's personal longevity, the public health, and the efficient use of healthcare dollars. As healthcare delivery models shift, the effects on patients and health outcomes achieved should be monitored, particularly for chronic diseases such as HIV. PMID- 27255097 TI - Improving Interdisciplinary Provider Communication Through a Unified Paging System. AB - OBJECTIVES: Interdisciplinary communication at a Veterans Affairs (VA) academic teaching hospital is largely dependent on alphanumeric paging, which has limitations as a result of one-way communication and lack of reliable physician identification. Adverse patient outcomes related to difficulty contacting the correct consulting provider in a timely manner have been reported. METHODS: House officers were surveyed on the level of satisfaction with the current VA communication system and the rate of perceived adverse patient outcomes caused by potential delays within this system. Respondents were then asked to identify the ideal paging system. These results were used to develop and deploy a new Web site. A postimplementation survey was repeated 1 year later. This study was conducted as a quality improvement project. RESULTS: House officer satisfaction with the preintervention system was 3%. The majority used more than four modalities to identify consultants, with 59% stating that word of mouth was a typical source. The preferred mode of paging was the university hospital paging system, a Web-based program that is used at the partnering academic institution. Following integration of VA consulting services within the university hospital paging system, the level of satisfaction improved to 87%. Significant decreases were seen in perceived adverse patient outcomes (from 16% to 2%), delays in patient care (from 90% to 16%), and extended hospitalizations (from 46% to 4%). CONCLUSIONS: Our study demonstrates significant improvement in physician satisfaction with a newly implemented paging system that was associated with a decreased perceived number of adverse patient events and delays in care. PMID- 27255098 TI - Was This Readmission Preventable? Qualitative Study of Patient and Provider Perceptions of Readmissions. AB - OBJECTIVES: Readmissions are a costly, burdensome, and potentially preventable occurrence in the healthcare system. With the renewed national focus on the cost and quality of health care, readmissions have become a major target for improvement; however, in general, the viewpoints of patients and healthcare providers have not been considered in these discussions. We aimed to compare provider and patient perspectives on the preventability of hospital readmissions. We also aimed to compare the factors that patients and providers perceive as contributing to readmissions. METHODS: We conducted descriptive statistics of readmissions using provider chart reviews (N = 213) on all readmissions to the University of North Carolina hospitalist service during a 6-month span. We also performed a qualitative analysis of those provider chart reviews, in addition to interviews with those readmitted patients (n = 23). We compared the percentage of providers versus patients who believed the readmission was preventable, and we explored the factors to which each group attributed the readmission. RESULTS: Providers stated that 30% of the readmissions were preventable, compared with only 13% of patients. Key contributing factors differed between providers and patients. Providers cited medical problems in 45% of readmissions, pain (24%), follow-up problems (22%), substance abuse (20%), and nonadherence (17%). Patients believed nothing could have been done to prevent them in 35% of readmissions, but they also cited medical problems (35%), incomplete diagnosis or treatment (22%), medication issues (17%), and system concerns (13%) as contributing to readmissions. CONCLUSIONS: These data suggest that patients and providers view the issue of readmissions differently and highlight potential areas for improvement. PMID- 27255099 TI - Root adaptations to soils with low fertility and aluminium toxicity. AB - BACKGROUND: Plants depend on their root systems to acquire the water and nutrients necessary for their survival in nature, and for their yield and nutritional quality in agriculture. Root systems are complex and a variety of root phenes have been identified as contributors to adaptation to soils with low fertility and aluminium (Al) toxicity. Phenotypic characterization of root adaptations to infertile soils is enabling plant breeders to develop improved cultivars that not only yield more, but also contribute to yield stability and nutritional security in the face of climate variability. SCOPE: In this review the adaptive responses of root systems to soils with low fertility and Al toxicity are described. After a brief introduction, the purpose and focus of the review are outlined. This is followed by a description of the adaptive responses of roots to low supply of mineral nutrients [with an emphasis on low availability of nitrogen (N) and phosphorus (P) and on toxic levels of Al]. We describe progress in developing germplasm adapted to soils with low fertility or Al toxicity using selected examples from ongoing breeding programmes on food (maize, common bean) and forage/feed (Brachiaria spp.) crops. A number of root architectural, morphological, anatomical and metabolic phenes contribute to the superior performance and yield on soils with low fertility and Al toxicity. Major advances have been made in identifying root phenes in improving adaptation to low N (maize), low P (common bean) or high Al [maize, common bean, species and hybrids of brachiariagrass, bulbous canarygrass (Phalaris aquatica) and lucerne (Medicago sativa)]. CONCLUSIONS: Advanced root phenotyping tools will allow dissection of root responses into specific root phenes that will aid both conventional and molecular breeders to develop superior cultivars. These new cultivars will play a key role in sustainable intensification of crop-livestock systems, particularly in smallholder systems of the tropics. Development of these new cultivars adapted to soils with low fertility and Al toxicity is needed to improve global food and nutritional security and environmental sustainability. PMID- 27255101 TI - Occipitocervical dissociation-incidence, evaluation, and treatment. AB - Traumatic occipitocervical dissociation (OCD) results from ligamentous injury to the craniocervical junction and is associated with a high rate of mortality and significant neurologic morbidity. The diagnosis is frequently missed on initial lateral cervical spinal radiographs mainly due to inadequate visualization of radiological landmarks and low degree of suspicion. Widespread availability of multidetector computed tomography (MDCT) of the spine and development of better diagnostic radiological criteria has allowed timely diagnosis and good clinical outcome following posterior occipitocervical fusion and instrumentation for a pathology that was once considered uniformly fatal. The present paper reviews the clinical features, diagnosis, and management of OCD in light of most recent literature. PMID- 27255100 TI - Optimal Imaging Strategies for Rectal Cancer Staging and Ongoing Management. AB - OPINION STATEMENT: Imaging determines the optimal treatment for rectal cancer patients. High-resolution magnetic resonance imaging (MRI) overcomes many of the known limitations of previous methods. When performed in accordance with the recommended standards, MRI enables accurate staging of both early and advanced rectal cancer, accurate response assessment, the delineation of recurrent disease and planning surgical treatment in a safe and effective manner. Tumour-related high-risk features with known adverse outcomes can be preoperatively identified and treated with neoadjuvant chemoradiotherapy. Further, MRI post-treatment tumour response assessment using TRG grading system also predicts the likely survival outcomes and in the future will be used to modify treatment further by stratification into good and poor responders. There is a paucity of literature with validated outcome data concerning use of diffusion-weighted imaging and positron emission tomography (PET)/computed tomography (CT), and in the absence of any validated methods and outcome data, their use in the initial assessment and restaging after treatment is limited to research protocols. Combination MRI and CT is essential for distant spread assessment and recurrent disease, and currently PET-CT is sometimes used in the workup of patients with recurrent and metastatic disease. PMID- 27255102 TI - Electrochemiluminescence (ECL) immunosensor for detection of Francisella tularensis on screen-printed gold electrode array. AB - An electrochemiluminescence (ECL) immunosensor for the rapid detection of the Francisella tularensis pathogen using whole antibodies or antibody fragments as capture biomolecule is described. A sandwich immunoassay was used with either lipopolysaccharide (LPS) or the whole inactivated bacterial cell (LVS) as a target, while Ru(bpy)3 (2+)-encapsulated silicate nanoparticles were linked to the secondary antibody and used as ECL labels. The assay was performed in a fluidic chip housed in a custom-built black box incorporating electronics, optics and fluidics. The obtained limit of detection for LPS was 0.4 ng/mL, while for the LVS it was 70 and 45 bacteria/mL when the capturing molecule was the whole antibody and the antibody F(ab) fragment, respectively. PMID- 27255103 TI - Ultra-sensitive film sensor based on Al2O3-Au nanoparticles supported on PDDA functionalized graphene for the determination of acetaminophen. AB - An electrochemical sensor of acetaminophen based on poly(diallyldimethylammonium chloride) (PDDA)-functionalized reduced graphene-loaded Al2O3-Au nanoparticles coated onto glassy carbon electrode (Al2O3-Au/PDDA/reduced graphene oxide (rGO)/glass carbon electrode (GCE)) were prepared by layer self-assembly technique. The as-prepared electrode-modified materials were characterized by scanning electron microscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy. The electrocatalytic performances of Al2O3-Au/PDDA/rGO modified glassy carbon electrode toward the acetaminophen were investigated by cyclic voltammetry and differential pulse voltammetry. The modified electrodes of graphene oxide (GO)/GCE, PDDA/rGO/GCE, and Al2O3-Au/PDDA/rGO/GCE were constructed for comparison and learning the catalytic mechanism. The research showed Al2O3 Au/PDDA/rGO/GCE having good electrochemical performance, attributing to the synergetic effect that comes from the special nanocomposite structure and physicochemical properties of Al2O3-Au nanoparticles and graphene. A low detection limit of 6 nM (S/N = 3) and a wide linear detection range from 0.02 to 200 MUM (R (2) = 0.9970) was obtained. The preparation of sensor was successfully applied for the detection of acetaminophen in commercial pharmaceutical pills. Graphical abstract Schematic diagram of synthesis of Al2O3-Au/PDDA/rGO/GCE. PMID- 27255105 TI - An analytical approach for the non-invasive selection of consolidants in rubber artworks. AB - The effectiveness of five polymeric materials for the long-term conservation and restoration of rubber artworks was evaluated by accelerated photo-oxidative degradation studies. Two different ethylene vinyl-acetate resins, generally used in industry and uncommon in conservation field, a new water-based polyurethane, and two ethylene butyl-acrylate resins were assessed for the consolidation of rubber. By monitoring their degradation along time with LED imaging coupled to statistics and Fourier transform infrared spectroscopy (FTIR), the polymeric materials with the best properties that ensure the protection and security of the artwork were identified. The degradation was performed in solar box simulating the light exposure in a museum, under controlled temperature at no more than 35 degrees C in order to exclude the thermal effects that could influence the ageing of polymers. The mechanical stress of the treated samples was also investigated. The spectroscopic analyses, the chromatic changes study, and the mechanical degradation were used as indicators of the consolidant stability, allowing the evaluation of the materials selected for the consolidation and conservation of rubber. The ethylene-vinyl acetate copolymers resulted the most stable and suitable for the conservation of rubber artworks. Lastly, the conservation treatment identified in this research was employed for the restoration of the contemporary artwork "Presagi di Birnam" made with bicycle inner tubes by the artist Carol Rama. PMID- 27255104 TI - Cyclometalated iridium(III) chelates-a new exceptional class of the electrochemiluminescent luminophores. AB - Recent development of the phosphorescent cyclometalated iridium(III) chelates has enabled, due to their advantageous electrochemical and photo-physical properties, important breakthroughs in many photonic applications. This particular class of 5d(6) ion complexes has attracted increasing interest because of their potential application in electroluminescence devices with a nearly 100 % internal quantum efficiency for the conversion of electric energy to photons. Similar to electroluminescence, the cyclometalated iridium(III) chelates have been successfully applied in the electricity-to-light conversion by means of the electrochemiluminescence (ECL) processes. The already reported ECL systems utilizing the title compounds exhibit extremely large ECL efficiencies that allow one to envisage many potential application for them, especially in further development of ECL-based analytical techniques. This review, based on recently published papers, focuses on the ECL properties of this very exciting class of organometallic luminophores. The reported work, describing results from fundamental as well as application-oriented investigations, will be surveyed and briefly discussed. Graphical abstract Depending on the chemical nature of the cyclometalated irdium(III) chelate different colours of the emitted light can be produced during electrochemical excitation. PMID- 27255106 TI - Stachybotrys mycotoxins: from culture extracts to dust samples. AB - The filamentous fungus Stachybotrys chartarum is known for its toxic metabolites and has been associated with serious health problems, including mycotoxicosis, among occupants of contaminated buildings. Here, we present results from a case study, where an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for known and tentatively identified compounds characterized via UHPLC-quadruple time-of-flight (QTOF) screening of fungal culture extracts, wall scrapings and reference standards. The UHPLC-MS/MS method was able to identify 12 Stachybotrys metabolites, of which four could be quantified based on authentic standards and a further six estimated based on similarity to authentic standards. Samples collected from walls contaminated by S. chartarum in a water-damaged building showed that the two known chemotypes, S and A, coexisted. More importantly, a link between mycotoxin concentrations found on contaminated surfaces and in settled dust was made. One dust sample, collected from a water-damaged room, contained 10 pg/cm(2) macrocyclic trichothecenes (roridin E). For the first time, more than one spirocyclic drimane was detected in dust. Spirocyclic drimanes were detected in all 11 analysed dust samples and in total amounted to 600 pg/cm(2) in the water damaged room and 340 pg/cm(2) in rooms adjacent to the water-damaged area. Their wide distribution in detectable amounts in dust suggested they could be good candidates for exposure biomarkers. Graphical abstract Stachybotrys growing on a gypsum board, and some of the compounds it produces. PMID- 27255107 TI - WHO recommends eight week abstinence or safer sex after return from Zika areas. PMID- 27255109 TI - Cryptic Species in Proechimys goeldii (Rodentia, Echimyidae)? A Case of Molecular and Chromosomal Differentiation in Allopatric Populations. AB - The spiny rats of the genus Proechimys have a wide distribution in the Amazon, covering all areas of endemism of this region. We analyzed the karyotype and cytochrome b (Cyt b) sequences in Proechimys goeldii from 6 localities representing 3 interfluves of the eastern Amazon. A clear separation of P. goeldii into 2 monophyletic clades was observed, both chromosomally and based on Cyt b sequences: cytotype A (2n = 26x2640;/27x2642;, NF = 42) for samples from the Tapajos-Xingu interfluve and cytotype B (2n = 24x2640;/25x2642;, NF = 42) for samples from the Xingu-Tocantins interfluve and east of the Tocantins River. The karyotypes differ in a pericentric inversion and a centric fusion/fission and an average nucleotide divergence of 6.1%, suggesting cryptic species. Meiotic analysis confirmed the presence of a XX/XY1Y2 multiple sex chromosome determination system for both karyotypes. The karyotypes also vary from the literature (2n = 24, NF = 42, XX/XY). The autosome translocated to the X chromosome is different both in size and morphology to P. cf. longicaudatus, which also has a multiple sex chromosome determination system (2n = 14x2640;/15x2640;x2642;/16x2640;/17x2642;, NF = 14). The Xingu River is a barrier that separates populations of P. goeldii, thus maintaining their allopatric nature and providing an explanation for the molecular and cytogenetic patterns observed for the Xingu River but not the Tocantins River. PMID- 27255108 TI - Genotypic and phenotypic detection of capsular polysaccharide and biofilm formation in Staphylococcus aureus isolated from bovine milk collected from Brazilian dairy farms. AB - Staphylococcus aureus is a pathogen that frequently causes mastitis in bovine herds worldwide. This pathogen produces several virulence factors, including cell associated adhesins, toxic and cytolytic exoproteins, and capsular polysaccharides. The aim of the present study was to test for the presence of genes involved in capsular polysaccharide production and biofilm formation in S. aureus isolated from bovine mastitis samples collected from 119 dairy herds located in three different Brazilian regions, as well as to assay the production of capsular polysaccharides and biofilm, in vitro. The detection of the cap, icaAD, and bap genes was performed using PCR. The detection and quantification of capsular polysaccharide production was performed using ELISA assays. The ability of the isolates to form a biofilm was examined using the polystyrene surface of microtiter plates. All 159 S. aureus isolates investigated harboured the cap gene: 80 % carried the cap5 gene and 20 % carried the cap8 gene. Sixty-nine percent of the isolates expressed capsular polysaccharide (CP) in vitro, 58 % expressed CP5 and 11 % expressed CP8. All of the isolates harboured the icaA and icaD genes, and 95.6 % of the isolates carried the bap gene. Of the 159 isolates analysed, 97.5 % were biofilm producers. A significant association between the capsular genotype and phenotype and the amount of biofilm formation was detected: cap5/CP5 isolates tended to form more biofilm and to produce a thinner CP layer than cap8/CP8 isolates. The results indicate a high potential for pathogenicity among S. aureus isolated from bovine milk collected from three different regions in Brazil. PMID- 27255110 TI - Decreased S100B expression in chronic liver diseases. AB - BACKGROUND/AIMS: Hepatic innervation in liver diseases is not fully understood. We here evaluated S100B expression as a marker of hepatic nerves in patients with various chronic liver diseases, topographically and semi-quantitatively. METHODS: Liver specimens were obtained from 70 subjects (three controls, and 32 chronic hepatitis B, 14 chronic hepatitis C, 14 liver cirrhosis, and seven hepatocellular carcinoma patients). The hepatic nerve density was calculated based on immunohistochemical staining of S100B protein in the portal tracts and hepatic lobules. S100B mRNA levels were semi-quantitatively assessed as the S100B/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA ratio. RESULTS: The densities of the hepatic nerves in portal tracts of chronic liver diseases were not significantly different from those of normal controls but the hepatic nerve densities in lobular areas of liver cirrhosis were significantly decreased (p = 0.025). Compared to the control, the S100B/GAPDH mRNA ratio was significantly decreased in chronic liver diseases (p = 0.006) and most decreased in chronic hepatitis C patients (p = 0.023). In chronic liver diseases, The S100B/GAPDH mRNA ratio tended to decrease as the fibrosis score > 0 (p = 0.453) but the overall correlation between the S100B/GAPDH mRNA ratio and fibrosis score was not statistically significant (r = 0.061, p = 0.657). CONCLUSIONS: Hepatic innervation is decreased in cirrhotic regenerating nodules compared to the control group and seems to decrease in early stages of fibrosis progression. Further studies are needed to clarify the association between changes of hepatic innervation and chronic liver disease progression. PMID- 27255111 TI - Why we need intravenous antiplatelet agents. AB - Oral ADP-receptor antagonists combined with aspirin are the standard for dual antiplatelet therapy (DAPT) during percutaneous coronary intervention (PCI). However, the oral route of administration of ADP-receptor antagonists leaves them vulnerable to unpredictable and often inadequate platelet inhibition at the time of PCI, while their prolonged effects often lead to the decision not to load them prior to PCI. Intravenous antiplatelet agents, including glycoprotein IIb/IIIa inhibitors (GPI) and cangrelor, a reversible P2Y12 inhibitor, address these shortcomings. In June 2015, the US FDA approved cangrelor for the prevention of thrombotic events associated with coronary stenting. This review examines the current state of peri-PCI DAPT and demonstrates that the selective use of GPIs and intravenous ADP-antagonist agents reduces the risk of periprocedural thrombosis. PMID- 27255112 TI - Redox Signaling and Bioenergetics Influence Lung Cancer Cell Line Sensitivity to the Isoflavone ME-344. AB - ME-344 [(3R,4S)-3,4-bis(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol] is a second-generation derivative natural product isoflavone presently under clinical development. ME-344 effects were compared in lung cancer cell lines that are either intrinsically sensitive or resistant to the drug and in primary immortalized human lung embryonic fibroblasts (IHLEF). Cytotoxicity at low micromolar concentrations occurred only in sensitive cell lines, causing redox stress, decreased mitochondrial ATP production, and subsequent disruption of mitochondrial function. In a dose-dependent manner the drug caused instantaneous and pronounced inhibition of oxygen consumption rates (OCR) in drug-sensitive cells (quantitatively significantly less in drug-resistant cells). This was consistent with targeting of mitochondria by ME-344, with specific effects on the respiratory chain (resistance correlated with higher glycolytic indexes). OCR inhibition did not occur in primary IHLEF. ME-344 increased extracellular acidification rates in drug-resistant cells (significantly less in drug-sensitive cells), implying that ME-344 targets mitochondrial proton pumps. Only in drug sensitive cells did ME-344 dose-dependently increase the intracellular generation of reactive oxygen species and cause oxidation of total (mainly glutathione) and protein thiols and the concomitant immediate increases in NADPH levels. We conclude that ME-344 causes complex, redox-specific, and mitochondria-targeted effects in lung cancer cells, which differ in extent from normal cells, correlate with drug sensitivity, and provide indications of a beneficial in vitro therapeutic index. PMID- 27255113 TI - Chiral Plasma Pharmacokinetics and Urinary Excretion of Bupropion and Metabolites in Healthy Volunteers. AB - Bupropion, widely used as an antidepressant and smoking cessation aid, undergoes complex metabolism to yield numerous metabolites with unique disposition, effect, and drug-drug interactions (DDIs) in humans. The stereoselective plasma and urinary pharmacokinetics of bupropion and its metabolites were evaluated to understand their potential contributions to bupropion effects. Healthy human volunteers (n = 15) were administered a single oral dose of racemic bupropion (100 mg), which was followed by collection of plasma and urine samples and determination of bupropion and metabolite concentrations using novel liquid chromatography-tandem mass spectrometry assays. Time-dependent, elimination rate limited, stereoselective pharmacokinetics were observed for all bupropion metabolites. Area under the plasma concentration-time curve from zero to infinity ratios were on average approximately 65, 6, 6, and 4 and Cmax ratios were approximately 35, 6, 3, and 0.5 for (2R,3R)-/(2S,3S)-hydroxybupropion, R-/S bupropion, (1S,2R)-/(1R,2S)-erythrohydrobupropion, and (1R,2R)-/(1S,2S) threohydrobupropion, respectively. The R-/S-bupropion and (1R,2R)-/(1S,2S) threohydrobupropion ratios are likely indicative of higher presystemic metabolism of S- versus R-bupropion by carbonyl reductases. Interestingly, the apparent renal clearance of (2S,3S)-hydroxybupropion was almost 10-fold higher than that of (2R,3R)-hydroxybupropion. The prediction of steady-state pharmacokinetics demonstrated differential stereospecific accumulation [partial area under the plasma concentration-time curve after the final simulated bupropion dose (300-312 hours) from 185 to 37,447 nM?h] and elimination [terminal half-life of approximately 7-46 hours] of bupropion metabolites, which may explain observed stereoselective differences in bupropion effect and DDI risk with CYP2D6 at steady state. Further elucidation of bupropion and metabolite disposition suggests that bupropion is not a reliable in vivo marker of CYP2B6 activity. In summary, to our knowledge, this is the first comprehensive report to provide novel insight into mechanisms underlying bupropion disposition by detailing the stereoselective pharmacokinetics of individual bupropion metabolites, which will enhance clinical understanding of bupropion's effects and DDIs with CYP2D6. PMID- 27255114 TI - Transcatheter closure of PFO as secondary prevention of cryptogenic stroke. AB - This article covers the main unsolved issues regarding the potential role that the patent foramen ovale (PFO) plays in the genesis of so-called cryptogenic stroke. Some brief notions of the anatomy and epidemiology of the PFO are outlined. Subsequently, the results of the three trials on secondary prevention (medical therapy vs. transcatheter closure) in patients with PFO and a history of cryptogenic stroke are presented. The conflicting results of numerous meta analyses derived from the three randomized controlled trials are discussed. Official scientific guidelines dispute an alleged superior efficacy of transcatheter PFO occlusion in comparison with antithrombotic therapy alone (anticoagulants or antiplatelet agents), except for selected cases of patients with documented PFO and a concomitant clinical-instrumental picture of deep venous thrombosis. Nevertheless, considering recent doubts about the presumptive thrombogenic and arrhythmogenic potential of PFO occlusion, which concerns only one of the septal occluders previously used, further in-depth investigations are warranted, centered on the use of newer dedicated devices to be tested in comparison with antithrombotic regimens alone. PMID- 27255115 TI - [Computed tomography in patients with chronic stable angina : Fractional flow reserve measurement]. AB - Coronary computed tomography angiography (cCTA) has been established for the non invasive diagnosis of coronary artery disease (CAD). Previous studies demonstrated the high diagnostic accuracy of cCTA, particularly for ruling out CAD. As a known limitation of cCTA a large number of visually significant coronary stenoses are found to be hemodynamically not relevant by invasive fractional flow reserve (FFR). CT-based FFR (CT-FFR) builds on recent advances in computational fluid dynamics and image simulation techniques. Along with CT myocardial perfusion imaging, CT-FFR is a promising approach towards a more accurate estimation of the hemodynamic relevance of coronary artery stenoses. CT FFR is derived from regular CT datasets without additional image acquisitions, contrast material, or medication. Two CT-FFR techniques can be differentiated. The initial method requires external use of supercomputers and has gained approval for clinical use in the USA. Furthermore, a prototype-software has been introduced which is less computationally demanding via integration of reduced order models for on-site calculation of CT-FFR. The present article reviews these methods in the context of available study results and meta-analyses. Furthermore, limitations and future concepts of CT-FFR are discussed. PMID- 27255116 TI - Results of pericardiectomy for constrictive pericarditis : Single-center experience. AB - BACKGROUND: We evaluated our early and late outcomes after pericardiectomy in patients with constrictive pericarditis (CP). PATIENTS AND METHODS: We retrospectively reviewed 31 patients who underwent pericardiectomy for CP from 1997 to 2015. Their mean age was 49.2 +/- 18.5 years and 74.2 % of them were male. The vast majority had severe functional impairment (NYHA class III-IV) with a mean duration of symptoms of 14.2 +/- 10.1 months. RESULTS: Early mortality was 9.7 %: n = 3; multiorgan failure (MOF) in 1, respiratory failure in 1, and left heart failure in 1. Preoperative systolic pulmonary artery pressure over 60 mmHg (p = 0.038, odds ratio [OR] = 0.12) and postoperative low cardiac output syndrome (p = 0.005, OR = 13.5) were significant predictors of early mortality in univariate analysis. Mean follow-up time was 57.8 +/- 61.9 months (4-216 months). Late mortality was 6.8 % (2/28 patients) and the cause was MOF secondary to end stage right heart failure. In Kaplan-Meier analyses, actuarial (including early mortality) and event-free survival rates were 83.9 and 51.1 % at 216 months, respectively. At the end of follow-up, the majority of patients (23/26, 92.9 %) were in good functional status (NYHA class I-II). There were fewer patients under diuretic therapy in the postoperative than in the preoperative period; however, the difference was not statistically significant (12/31 vs. 4/26, p = 0.76). There was no significant difference between the preoperative and follow-up tricuspid annular plane systolic excursion values (15.5 +/- 2.2 and 16.6 +/- 2.2 mm, respectively, p = 0.088). Left ventricular systolic function was preserved in all patients postoperatively. CONCLUSION: Although early mortality after pericardiectomy remains high, the procedure provides significant improvement in functional status in the long term. PMID- 27255117 TI - [Coronary microvascular dysfunction : Clinical aspects, diagnosis and therapy]. AB - Just as in epicardial coronary stenosis, coronary microvascular dysfunction (CMD) also leads to an imbalance of myocardial oxygen supply and demand. The dysfunction is located at the level of the coronary microcirculation with vessel diameters < 500 um and structural as well as functional alterations have been described. The underlying mechanisms are diverse, frequently overlap and are still incompletely understood. Among others, conditions such as chronic inflammation, estrogen deficiency and a genetic familial predisposition have been reported. A common and often underdiagnosed clinical manifestation of CMD is found in patients who have symptoms of angina pectoris but no obstructive epicardial coronary artery disease or myocardial disease. The CMD can be diagnosed using non-invasive procedures, such as the combination of coronary computed tomography (CT) angiography and cardiac stress magnetic resonance imaging (MRI) or coronary CT and positron emission tomography (PET). In addition, invasive coronary vasomotor assessment is also suitable. Very little evidence is available regarding the effectiveness of pharmacological treatment of CMD. The current European Society of Cardiology (ESC) guidelines on the management of stable coronary artery disease from 2013 recommend using acetylsalicylic acid (ASS) and a statin as well as beta blockers and/or calcium channel blockers. Patients with CMD have an elevated risk for coronary events and death of approximately 1.7 % per year. Moreover, there is an increased morbidity with frequent presentations in practices and emergency admissions. Clinical research efforts should aim at a better characterization of the underlying mechanisms of CMD in order to develop targeted treatment approaches. PMID- 27255118 TI - Packaging colour research by tobacco companies: the pack as a product characteristic. AB - BACKGROUND: Tobacco companies use colour on cigarette packaging and labelling to communicate brand imagery, diminish health concerns, and as a replacement for prohibited descriptive words ('light' and 'mild') to make misleading claims about reduced risks. METHODS: We analysed previously secret tobacco industry documents to identify additional ways in which cigarette companies tested and manipulated pack colours to affect consumers' perceptions of the cigarettes' flavour and strength. RESULTS: Cigarette companies' approach to package design is based on 'sensation transference' in which consumers transfer sensations they derive from the packaging to the product itself. Companies manipulate consumers' perceptions of the taste and strength of cigarettes by changing the colour of the packaging. For example, even without changes to the tobacco blends, flavourings or additives, consumers perceive the taste of cigarettes in packages with red and darker colours to be fuller flavoured and stronger, and cigarettes in packs with more white and lighter colours are perceived to taste lighter and be less harmful. CONCLUSIONS: Companies use pack colours to manipulate consumers' perceptions of the taste, strength and health impacts of the cigarettes inside the packs, thereby altering their characteristics and effectively creating new products. In countries that do not require standardised packaging, regulators should consider colour equivalently to other changes in cigarette characteristics (eg, physical characteristics, ingredients, additives and flavourings) when making determinations about whether or not to permit new products on the market. PMID- 27255119 TI - Variations of toxic and carcinogenic constituents in nasvai: call for systematic research and regulation. PMID- 27255120 TI - Methods for the detection of reactive oxygen species employed in the identification of plant photosensitizers. AB - Over the past ten years, alternative methods for the rapid screening of PSs have been developed. In the present work, a study was undertaken to correlate the phototoxicity of plant extracts on either prokaryotic or eukaryotic cells, with the total oxidation status (TOS) as well as with their ability to produce 1O2. Results demonstrated that the extracts containing PSs that were active either on eukaryotic cells or bacteria increased their TOS after illumination, and that there was a certain degree of positive correlation between the extract phototoxic efficacy and TOS levels. The production of 1O2 by the illuminated extracts was indirectly measured by the use of the fluorescence of "singlet oxygen sensor green", which is a method that has proved highly sensitive for such measurement. 1O2 was detectable only upon illumination of the most active extracts. In addition, the oxidation of tryptophan and was employed as a method capable of measuring ROS generated by both type I and II ROS reactions. However, it turned out to be not sensitive enough to detect the species generated by plant extracts. Results demonstrated that the TOS method, initially developed to measure the oxidant status in plasma, can be readily applied to plant extracts. Unlike the method used to detect 1O2, the method employed for the detection of TOS proved to be accurate, since all the extracts that displayed a high phototoxic activity on either prokaryotic or eukaryotic cells, presented high TOS levels after illumination. PMID- 27255121 TI - Pharmacokinetic Characterization and Bioavailability of Strawberry Anthocyanins Relative to Meal Intake. AB - Plasma strawberry anthocyanins were characterized in overweight (BMI: 26 +/- 2 kg/m(2)) adults (n = 14) on the basis of meal timing. At each visit, subjects ingested three study drinks: two control and one strawberry drink. A strawberry drink was given at either 2 h before the breakfast meal (BM), with the meal (WM), or 2 h after the meal (AM), and control drinks were given at the alternative time points. Plasma anthocyanins and their metabolic conjugates were assessed hourly for 10 h using a triple-quadrupole liquid chromatography mass spectrometer. Maximum concentrations (Cmax), area under the curve (AUC), and bioavailability of pelargonidin-based anthocyanins determined from the main conjugated metabolite (pelargonidin glucuronide) were greater when a strawberry drink was consumed 2 h before the meal (BM) compared to consumption WM or AM (p < 0.05). Our results indicate that the timing of strawberry consumption relative to a meal impacts anthocyanin pharmacokinetic variables. PMID- 27255122 TI - CO2 leaking from sub-seabed storage: Responses of two marine bacteria strains. AB - Carbon capture and storage (CCS) in stable geological locations is one of the options to mitigate the negative effects of global warming produced by the increase in CO2 concentrations in the atmosphere. A CO2 leak is one of the risks associated with this strategy. Marine bacteria attached to the sediment may be affected by an acidification event. Responses of two marine strains (Roseobacter sp. CECT 7117 and Pseudomonas litoralis CECT 7670) were assessed under different scenarios using a range of pH values (7.8, 7, 6.5, 6, and 5.5) to mimic a CO2 leak. A CO2 injection system was used to simulate an escape from a stable sub seabed. Growth rate (MU), cell number, inhibition of Relative Inhibitory Effect (RI CO2) and inhibited population were analysed as endpoints. P. litoralis showed more sensitivity to high CO2 concentrations than Roseobacter sp. Our results highlight the diversity and resistance in marine bacteria and their capacity to adapt under a stressful CO2 leakage. PMID- 27255123 TI - Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates. AB - Widespread contamination of coastal environments by emerging compounds includes low concentrations of pharmaceuticals. These pollutants are not currently incorporated in monitoring programs despite their effects on non-target organisms are very little documented. Among the selective serotonin reuptake inhibitor (SSRI) antidepressants, sertraline (SRT) is one of the most prescribed globally. In this work, earlier life stages of Amphibalanus amphitrite, Brachionus plicatilis and Mytilus galloprovincialis were exposed to environmental concentrations of SRT in order to study both sub-lethal and lethal responses in 24/48 h-tests. Low concentrations of SRT altered significantly swimming behavior in A. amphitrite and B. plicatilis giving 48 h-EC50 (MUg/L) of 113.88 and 282.23, respectively whereas higher values were observed for mortality and immobilization. EC50 embryotoxicity with M. galloprovincialis was 206.80 MUg/L. This work add new data about SRT ecotoxicity on marine invertebrates and confirms the applicability of behavioral endpoints to evaluate the environmental impact of antidepressants in marine organisms. PMID- 27255124 TI - Plant species effects on soil nutrients and chemistry in arid ecological zones. AB - The presence of vegetation strongly influences ecosystem function by controlling the distribution and transformation of nutrients across the landscape. The magnitude of vegetation effects on soil chemistry is largely dependent on the plant species and the background soil chemical properties of the site, but has not been well quantified along vegetation transects in the Great Basin. We studied the effects of plant canopy cover on soil chemistry within five different ecological zones, subalpine, montane, pinyon-juniper, sage/Mojave transition, and desert shrub, in the Great Basin of Nevada all with similar underlying geology. Although plant species differed in their effects on soil chemistry, the desert shrubs Sarcobatus vermiculatus, Atriplex spp., Coleogyne ramosissima, and Larrea tridentata typically exerted the most influence on soil chemistry, especially amounts of K(+) and total nitrogen, beneath their canopies. However, the extent to which vegetation affected soil nutrient status in any given location was not only highly dependent on the species present, and presumably the nutrient requirements and cycling patterns of the plant species, but also on the background soil characteristics (e.g., parent material, weathering rates, leaching) where plant species occurred. The results of this study indicate that the presence or absence of a plant species, especially desert shrubs, could significantly alter soil chemistry and subsequently ecosystem biogeochemistry and function. PMID- 27255125 TI - Intraoperative radiotherapy in elderly patients with breast cancer: Is there a clinical applicability? Review of the current evidence. AB - INTRODUCTION: Screening and adjuvant postoperative therapies have increased survival amongst women with breast cancer, but these tools are seldom applied in elderly patients. Higher rates of local recurrence occur in those elderly patients who avoid radiotherapy. TARGIT-A and ELIOT trials has been reported to not to be inferior to external beam RT in suitable subgroups of patients. The TARGIT-Elderly trial has been launched in order to confirm the efficacy of intraoperative radiotherapy (IORT) in a well selected group of elderly patients who are more likely to decline radiation treatment. OBJECTIVES: Current evidence of the medical literature on the clinical reliability and applicability of intraoperative radiotherapy amongst older women diagnosed with early breast cancer is after summarized. MATERIALS AND METHODS: Literature databases were searched up to June 2015. Terms used to retrieve articles were 'breast cancer', 'elderly', 'intraoperative radiotherapy', 'IORT' and 'IOERT'. RESULTS: Elderly patients with pT1N0 tumours are regarded to be suitable for IORT according to ASTRO and GEC-ESTRO recommendations, respectively. DISCUSSION: In the light of the medical literature we can assume that patients benefit from postoperative radiation therapy, but we still do not know who can be spared from it. These issues emphasize the urgent need to develop and support clinical trials for this older population of breast cancer patients. CONCLUSIONS: Whether radiotherapy is beneficial in elderly still remains a matter of debate. IORT along with BCS in a selected subgroup of patients (>70years, pT1N0 tumours) could represent a valid option for a better local control. PMID- 27255126 TI - Physiopathology and clinical considerations of laparoscopic surgery in the elderly. AB - OBJECTIVE: The marked improvements in medical technology and healthcare, lead an increasing number of elderly patients to take advantage of even complex surgical. Recently, laparoscopic surgery has been accepted as a minimally invasive treatment to reduce the morbidity after conventional surgery, and a number of studies have demonstrated the feasibility of laparoscopy with significant advantages also in the elderly. On the other side, the laparoscopic procedure has some drawbacks, including prolonged operation time and impact of carbon dioxide pneumoperitoneum on circulatory and respiratory dynamics. This paper will review the physiopathological implications of laparoscopy, as well as the current literature concerning the most common laparoscopic procedures that are increasingly performed in elderly patients. MATERIALS AND METHODS: A systematic review of the current literature was performed using the search engines EMBASE and PubMed to identify all studies reporting the physiopathological implications of laparoscopy in the elderly. The MeSH search terms used were "laparoscopy in the elderly", "physiopathology of laparoscopy", and "pneumoperitoneum". Multiple combinations of the keywords and MeSH terms were used with particular reference to elderly patients. RESULTS: Although laparoscopy is minimally invasive in its dissection techniques, the increased physiologic demands present particular challenges among elderly patients. CONCLUSIONS: Laparoscopy and its safety in the elderly patients remains a challenge and the evaluation of this approach is therefore mandatory. Although many studies have demonstrated the applicability and advantages of the laparoscopy also in the geriatric population, with low rates of morbidity and mortality, in elderly patients undergoing general surgical procedures the physiologic demands of laparoscopy should be carefully considered. PMID- 27255127 TI - Spirometry in elderly laryngectomized patients: A feasibility study. AB - BACKGROUND: Laryngeal cancer is the second most common respiratory neoplasm after lung cancer. Laryngectomy is a well established treatment for larynx cancers which involve relevant anatomic alterations. Spirometry is an essential investigation tool for diagnosis and severity of respiratory diseases, difficult to perform in laryngectomees. METHODS: 43 consecutive laryngectomized patients were enrolled from July 2014 to March 2015. Patients fulfilling inclusion criteria underwent spirometry at baseline assessment and after two days. During the examination, the spirometer was placed directly on the stoma of the patient, through mouthpiece "Spirometry Filter 74". RESULTS: At baseline, 26 eligible laryngectomees correctly performed the spirometry test with mouthpiece adhering to the stoma; 4 patients refused to perform the second spirometry after 2 days. The feasibility of spirometry examination in these patients was 100% despite difficulties in the execution of the test. The Pearson coefficient of reproducibility for FEV1, FVC and Tiffeneau Index was, respectively, 0.98, 0.94 and 0.77. DISCUSSION: Spirometry in laryngectomee patients is a feasible procedure for assessment of respiratory function; despite technical difficulties in the execution of the test, our results underline the reproducibility and repeatability of the spirometry. In conclusion, when performed within dedicated respiratory pathophysiology unit, spirometry is a reliable tool in the assessment and follow up of laryngectomees. PMID- 27255128 TI - Surgeon's clinical valuation and accuracy of ultrasound in the diagnosis of acute appendicitis: A comparison with intraoperative evaluation. Five years experience. AB - INTRODUCTION: Acute appendicitis is the most common cause of acute abdomen in adolescents, with an overall incidence of 7%. Two such tools are used to diagnose acute appendicitis: ultrasound and Computer Tomography imaging. End point of this study was to verify the accuracy of ultrasound imaging in the diagnosis of acute appendicitis with respect to intraoperative observations and the respective clinical and laboratory findings in young and in the elderly. METHODS: We considered all the appendectomies for acute appendicitis performed between 1 January 2010 and 1 January 2015. We evaluated clinical symptoms, laboratory findings, ultrasound findings, intraoperative signs, and anatomical and pathological findings. In the study we compared the ultrasound and intraoperative findings and then compared these with the respective clinical and laboratory data. RESULTS: In a comparison of diagnostic accuracy, the difference between clinical and ultrasound examinations was not significant. The differences between the diagnostic accuracy of clinical and laboratory findings and between ultrasound and laboratory investigations were statistically significant. CONCLUSION: We defined white blood cells and C protein levels as non-diagnostic of the type of acute inflammation but rather as indicators of the severity of the inflammatory process. We also agree with the authors who proposed the incorporation of ultrasonography into routine practice in the diagnosis of acute appendicitis, but only and exclusively to support other diagnostic procedures and preferably within emergency departments. A thorough clinical examination of patients with suspected acute appendicitis is still the best diagnostic procedure available to us. PMID- 27255129 TI - The thyroid disease in the elderly: Our experience. AB - INTRODUCTION: The number of elderly people in Italy is growing, so it is important to study the presentation of diseases in these subjects. MATERIALS AND METHODS: We selected 1362 patients who underwent thyroidectomy for different thyroid diseases from January 2008 to December 2014. The patients weredivided into two groups, according to the age. The patients aged 65 years and over were included in the group A, and the patients under the age of 65 years were included in the group B. DISCUSSION: Thyroid diseases in the elderly often present with atypical symptoms which are very similar to symptoms of the aging process. In elderly hypothyroidism occurs frequently sub-clinically and hyperthyroidism is often presented with cardiovascular symptoms. In our study we evaluated the differences in incidence of thyroid diseases in the elderly and in the younger groups of patients. CONCLUSION: The data analyzed in this study showed that in the elderly we have a reduced secretion and metabolization of thyroid hormones. The symptomatology in the elderly is nonspecific and can create a delay in the correct diagnosis. PMID- 27255130 TI - Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers. AB - Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. Hepatic IRI can seriously impair liver function, even producing irreversible damage, which causes a cascade of multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of ROS, intracellular Ca(2+) overload, cytokines and chemokines produced by KCs and neutrophils, and NO, are involved in the regulation of hepatic IRI processes. Matrix Metalloproteinases (MMPs) can be an important mediator of early leukocyte recruitment and target in acute and chronic liver injury associated to ischemia. MMPs and neutrophil gelatinase-associated lipocalin (NGAL) could be used as markers of I-R injury severity stages. This review explores the relationship between factors and inflammatory pathways that characterize hepatic IRI, MMPs and current pharmacological approaches to this disease. PMID- 27255131 TI - Pre-surgical bronchoscopic treatment for typical endobronchial carcinoids. AB - Carcinoids are tumors that originate from diffuse neuroendocrine system cells (APUD cells) and represent 1-2% of all pulmonary tumors. Although surgical resection remains the mainstay of treatment, bronchoscopic radical resection of typical carcinoids in selected cases exhibiting endoluminal growth and small implant base has also been explored. Bronchoscopic removal of endobronchial lesions may also reduce the risk of post-obstructive infections and improve pulmonary function, allowing the patient to undergo surgery in better clinical and respiratory state. In this paper we have evaluated the impact on surgical planning and outcome of preoperative bronchoscopic resection in treatment of endobronchial typical carcinoids. Our observations further support the role of bronchoscopic treatment before surgery in endobronchial typical carcinoids. PMID- 27255132 TI - Diagnostic value of computed tomography colonography (CTC) after incomplete optical colonoscopy. AB - INTRODUCTION: This study evaluated the role of computed tomography colonography (CTC) in patients who previously underwent incomplete optical colonoscopy (OC). We analyzed the impact of colonic lesions in intestinal segments not studied by OC and extracolonic findings in these patients. METHODS: Between January 2014 and May 2015, 61 patients with a history of abdominal pain and incomplete OC examination were studied by CTC. CTCs were performed by 320-row CT scan in both the supine and the prone position, without intravenous administration of contrast medium. In all patients both colonic findings and extracolonic findings were evaluated. RESULTS: Among the study group, 24 CTC examinations were negative for both colonic and extracolonic findings while 6 examinations revealed the presence of both colonic and extracolonic findings. In 24 patients CTC depicted colonic anomalies without extracolonic ones, while in 7 patients it showed extracolonic findings without colonic ones. DISCUSSION: CTC is a noninvasive imaging technique with the advantages of high diagnostic performance, rapid data acquisition, minimal patient discomfort, lack of need for sedation, and virtually no recovery time. CTC accurately allows the evaluation of the nonvisualized part of the colon after incomplete OC and has the distinct advantage to detect clinically important extracolonic findings in patients with incomplete OC potentially explaining the patient's symptoms and conditioning their therapeutic management. CONCLUSION: CTC accurately allows the assessment of both colonic and extracolonic pathologies representing a useful diagnostic tool in patients for whom complete OC is not achievable. PMID- 27255133 TI - Laparoscopic single site (LESS) and classic video-laparoscopic cholecystectomy in the elderly: A single centre experience. AB - Laparoscopic cholecystectomy (LC) is the gold-standard surgical method used to treat gallbladder diseases. Recently Laparoendoscopic single site surgery (LESS) has gained greater interest and diffusion for the surgical treatment of several pathologies. In elderly patients, just few randomized controlled trials are present in the literature that confirm the clinical advantages of LESS compared with the classic laparoscopic procedures. We present in this paper the preliminary results of this randomized prospective study regarding the feasibility and safety of LESS cholecystectomy versus classic laparoscopic technique. We demonstrated that LESS technique compared with traditional technique show some advantages like: acceptable operative times, lower post operative discomfort and sometimes reduction added complications. In addition we also demonstrate that fewer incisions and less scarring which mean less pain, and fewer parietal complications are related to this surgical procedure. In conclusion in the elderly LESS cholecystectomy technique is to be considered a suitable alternative to traditional three-port cholecystectomy. PMID- 27255134 TI - Short-course radiotherapy in elderly women with breast cancer: Comparison by age, comorbidity index and toxicity. AB - BACKGROUND: Breast cancer is the most common malignancy amongst elderly women. It represents the main cause of mortality for those women and it is steadily increasing. The primary therapeutic approach remains surgery, as in other age groups. The role of radiotherapy following surgery is still debated. The use of hypofractionated schedules is challenging the standard fractionation and has now been considered an advantageous option within this subgroup of patients. Results from randomized controlled trials have not been shown to be inferior to standard fractionation in terms of local recurrence, disease-free survival and overall survival. Acute and late side effects were not increased by hypofractionated regimens. PATIENTS AND METHODS: 60 elderly women treated by hypofractionated radiotherapy after breast conserving surgery were stratified by age. Comorbidities associated compliance and toxicity correlation to age were the first endpoints of the study. Comorbidity associated compliance was calculated by Cumulative Illness Rating Scale Geriatric. RESULTS: At a median follow-up of 15 months overall survival was 100%, without severe late toxicity. No statistical significant differences were found between Cumulative Illness Rating Scale Geriatric, systemic therapy and toxicity. CONCLUSION: In our experience hypofractioned regimens seem to be safe and reliable in the elderly setting, although longer follow up is needed. PMID- 27255135 TI - Homeostasis, singularities, and networks. AB - Homeostasis occurs in a biological or chemical system when some output variable remains approximately constant as an input parameter [Formula: see text] varies over some interval. We discuss two main aspects of homeostasis, both related to the effect of coordinate changes on the input-output map. The first is a reformulation of homeostasis in the context of singularity theory, achieved by replacing 'approximately constant over an interval' by 'zero derivative of the output with respect to the input at a point'. Unfolding theory then classifies all small perturbations of the input-output function. In particular, the 'chair' singularity, which is especially important in applications, is discussed in detail. Its normal form and universal unfolding [Formula: see text] is derived and the region of approximate homeostasis is deduced. The results are motivated by data on thermoregulation in two species of opossum and the spiny rat. We give a formula for finding chair points in mathematical models by implicit differentiation and apply it to a model of lateral inhibition. The second asks when homeostasis is invariant under appropriate coordinate changes. This is false in general, but for network dynamics there is a natural class of coordinate changes: those that preserve the network structure. We characterize those nodes of a given network for which homeostasis is invariant under such changes. This characterization is determined combinatorially by the network topology. PMID- 27255137 TI - Metabolic engineering of Corynebacterium glutamicum for methionine production by removing feedback inhibition and increasing NADPH level. AB - Relieving the feedback inhibition of key enzymes in a metabolic pathway is frequently the first step of producer-strain construction by genetic engineering. However, the strict feedback regulation exercised by microorganisms in methionine biosynthesis often makes it difficult to produce methionine at a high level. In this study, Corynebacterium glutamicum ATCC 13032 was metabolically engineered for methionine production. First, the metD gene encoding the methionine uptake system was deleted to achieve extracellular accumulation of methionine. Then, random mutagenesis was performed to remove feedback inhibition by metabolic end products. The resulting strain C. glutamicum ENM-16 was further engineered to block or decrease competitive branch pathways by deleting the thrB gene and changing the start codon of the dapA gene, followed by point mutations of lysC (C932T) and pyc (G1A, C1372T) to increase methionine precursor supply. To enrich the NADPH pool, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the pentose phosphate pathway were mutated to reduce their sensitivity to inhibition by intracellular metabolites. The resultant strain C. glutamicum LY-5 produced 6.85 +/- 0.23 g methionine l(-1) with substrate-specific yield (Y P/S) of 0.08 mol per mol of glucose after 72 h fed-batch fermentation. The strategies described here will be useful for construction of methionine engineering strains. PMID- 27255136 TI - Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose. AB - INTRODUCTION: Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients. METHODS: This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity. RESULTS: Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108). CONCLUSIONS: In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana. PMID- 27255138 TI - Hyphomonas pacifica sp. nov., isolated from deep sea of the Pacific Ocean. AB - Three Gram-negative, aerobic, non-spore-forming, oval- to pear-shaped bacterial strains (T16B2(T), T24B3, and C76AD) were isolated from petroleum-degrading microbial communities through an enrichment of sediments and seawater samples from the Pacific Ocean. Phylogenetic analysis showed strains T16B2(T), T24B3, and C76AD to form a robust clade together with Hyphomonas atlanticus 22II1-22F38(T) and Hyphomonas beringensis 25B14_1(T) (16S rRNA identity >=99.6 %). Genomic average nucleotide identity and DNA-DNA hybridization estimate values between strain T16B2(T) and nine type strains of the genus Hyphomonas are in the range of 82.9-88.2 and 18.3-33.6 %, respectively. The major cellular fatty acids in strains T16B2(T), T24B3, and C76AD are C16:0, C17:0, C18:1 omega7c-methyl, and summed feature 8 (C18:1 omega6c/omega7c). The DNA G+C content of strain T16B2(T) is 58.5 %. The predominant respiratory quinone of strain T16B2(T) is Q-11. Polar lipids comprise three unidentified glycolipids, one unidentified phospholipid, and two polar lipids. Combined phenotypic and genotypic data show strains T16B2(T), T24B3, and C76AD to represent a novel species of the genus Hyphomonas, for which the name Hyphomonas pacifica sp. nov. is proposed, with type strain T16B2(T) (=LMG 27911(T) = MCCC 1A04387(T)). PMID- 27255139 TI - Investigation of genes involved in nisin production in Enterococcus spp. strains isolated from raw goat milk. AB - Different strains of Lactococcus lactis are capable of producing the bacteriocin nisin. However, genetic transfer mechanisms allow the natural occurrence of genes involved in nisin production in members of other bacterial genera, such as Enterococcus spp. In a previous study, nisA was identified in eight enterococci capable of producing antimicrobial substances. The aim of this study was to verify the presence of genes involved in nisin production in Enterococcus spp. strains, as well as nisin expression. The nisA genes from eight Enterococcus spp. strains were sequenced and the translated amino acid sequences were compared to nisin amino-acid sequences previously described in databases. Although containing nisin structural and maturation related genes, the enterococci strains tested in the present study did not present the immunity related genes (nisFEG and nisI). The translated sequences of nisA showed some point mutations, identical to those presented by Lactococcus strains isolated from goat milk. All enterococci were inhibited by nisin, indicating the absence of immunity and thus that nisin cannot be expressed. This study demonstrated for the first time the natural occurrence of nisin structural genes in Enterococcus strains and highlights the importance of providing evidence of a link between the presence of bacteriocin genes and their expression. PMID- 27255140 TI - Identification of Cryptic Novel alpha-Galactosidase A Gene Mutations: Abnormal mRNA Splicing and Large Deletions. AB - Anderson-Fabry (FD) disease is an inborn error of metabolism caused by a deficiency of alpha-galactosidase A (GLA), a lysosomal enzyme. Many male FD patients display a classic FD phenotype; however, some female patients have neither reduced leukocyte GLA enzyme activity level nor FD symptoms. Thus, GLA gene analysis is especially important for diagnosing suspected FD in female subjects. In this study, we revealed 4 novel GLA gene mutations in 5 independent families using GLA cDNA analysis and multiplex ligation-dependent probe amplification (MLPA) analysis. These distinct mutations included a large deletion mutation from intron 1 to exon 5 (c.195-471_c.691del5.5k, corresponding to g.8508_g.14069del5.5k), an insertion mutation of splicing enhancer sequence in intron 4 (c.639+329_c.639+330ins113, corresponding to g.12627_g.12628ins113), an insertion mutation of retrotransposon L1 in exon 4 (c.634_c.635, corresponding to g.12293_g.12294), and a non-SNP deep intronic point mutation in intron 3 (c.547+395G>C, corresponding to g.11727G>C). It is difficult to detect these mutations with direct sequencing of only the exonic element. When exonic mutations are not found in the GLA gene from suspected FD patients, GLA cDNA and MLPA analyses should be performed to detect large deletion/insertion and intronic mutations including transcription abnormalities. PMID- 27255141 TI - Binuclear Cells in the Lactating Mammary Gland: New Insights on an Old Concept? AB - In a recent paper (Rios et al. Nat Commun. 7:11400, 2016), it was reported that polyploid cells are frequent in lactating mammary tissues. This phenomenon was observed in mammary tissue sampled from five separate mammalian species. According to that report, these binucleated cells occur late in pregnancy and early in lactation. Unfortunately, this paper did not mention a number of earlier observations and findings that remain pertinent to this day (Banerjee et al. Life sciences Pt 2: Biochemistry, general and molecular biology. 10(15):867-77, 1971; Banerjee MR, Wagner JE. Biochem. Biophys. Res. Commun. 49(2):480-7, 1972). In these classical experiments, the authors demonstrated in vivo that DNA synthesis continued without commensurate cell division during late pregnancy and lactation, and that this DNA synthesis was imperative for functional differentiation of the mammary epithelium. Later studies showed that DNA synthesis was indispensable to the induction of milk protein production in explant cultures of mammary tissue from unprimed, nulliparous mice. This dependence on DNA synthesis in mammary explant cultures stimulated by lactogenic hormones was found to be dispensable following a single pregnancy. The absolute requirement for DNA synthesis in nulliparous mouse mammary explants stimulated to synthesize milk protein in vitro has remained unexplained, as has the need for DNA synthesis prior to the onset of lactation. From a historical perspective, it is more likely that binuclear secretory cells in the lactating mammary gland are a consequence of the DNA synthesis requirement for lactation, rather than an essential element. PMID- 27255142 TI - Epidemiology of Nonfatal Injuries Among Schoolchildren. AB - Nonfatal injuries are considered as one of the major public health hazards affecting schoolchildren, and the majority of these injuries occur at school or in the home. A cross-sectional study was conducted over a period of 3 months, March-May 2015. The participants were 4,355 Jordanian schoolchildren in Grades 7 12. The Pearson chi(2) test was computed, and the odds ratio was used to determine the magnitude of various risk factors for nonfatal injuries among schoolchildren. The overall incidence of nonfatal injury was 33.9%. The group most likely to sustain nonfatal injuries was boys, aged 12-15, in Grade 7, whose parents had a low level of education or a high family income. Injury prevention in schools and at homes is a cornerstone for protection or reducing the incidence of injuries. School nurses have a duty to follow up and examine the accident reports and evaluate whether safety policies are applied and are effective in different school settings. Furthermore, health and education authorities should develop a national program for preventing injuries. PMID- 27255143 TI - Comments on "Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors". PMID- 27255144 TI - Higher mortality rates amongst emergency patients admitted to hospital at weekends reflect a lower probability of admission. AB - Objective Patients admitted as emergencies to hospitals at the weekend have higher death rates than patients admitted on weekdays. This may be because the restricted service availability at weekends leads to selection of patients with greater average severity of illness. We examined volumes and rates of hospital admissions and deaths across the week for patients presenting to emergency services through two routes: (a) hospital Accident and Emergency departments, which are open throughout the week; and (b) services in the community, for which availability is more restricted at weekends. Method Retrospective observational study of all 140 non-specialist acute hospital Trusts in England analyzing 12,670,788 Accident and Emergency attendances and 4,656,586 emergency admissions (940,859 direct admissions from primary care and 3,715,727 admissions through Accident and Emergency) between April 2013 and February 2014.Emergency attendances and admissions to hospital and deaths in any hospital within 30 days of attendance or admission were compared for weekdays and weekends. Results Similar numbers of patients attended Accident and Emergency on weekends and weekdays. There were similar numbers of deaths amongst patients attending Accident and Emergency on weekend days compared with weekdays (378.0 vs. 388.3). Attending Accident and Emergency at the weekend was not associated with a significantly higher probability of death (risk-adjusted OR: 1.010). Proportionately fewer patients who attended Accident and Emergency at weekend were admitted to hospital (27.5% vs. 30.0%) and it is only amongst the subset of patients attending Accident and Emergency who were selected for admission to hospital that the probability of dying was significantly higher at the weekend (risk-adjusted OR: 1.054). The average volume of direct admissions from services in the community was 61% lower on weekend days compared to weekdays (1317 vs. 3404). There were fewer deaths following direct admission on weekend days than weekdays (35.9 vs. 80.8). The mortality rate was significantly higher at weekends amongst direct admissions (risk-adjusted OR: 1.212) due to the proportionately greater reduction in admissions relative to deaths. Conclusions There are fewer deaths following hospital admission at weekends. Higher mortality rates at weekends are found only amongst the subset of patients who are admitted. The reduced availability of primary care services and the higher Accident and Emergency admission threshold at weekends mean fewer and sicker patients are admitted at weekends than during the week. Extending services in hospitals and in the community at weekends may increase the number of emergency admissions and therefore lower mortality, but may not reduce the absolute number of deaths. PMID- 27255146 TI - Platelet-rich plasma reduces the oxidative damage determined by a skeletal muscle contusion in rats. AB - Platelet-rich plasma (PRP) has received increasing attention and is widely used in clinical practice in order to stimulate human tissue healing. Contusions are very common injuries observed in sports and affect the function of the musculoskeletal system. This study investigated the effects of PRP on the oxidative damage determined by a contusion induced in gastrocnemius muscle of rats. PRP was injected intramuscularly immediately after injury and every 48 h, and the biochemical analysis was performed 1, 3, 5, or 7 days after the contusion onset in order to evaluate the changes characteristics of the healing process. The contusion increased the levels of oxidative stress markers such as thiobarbituric acid reactive substances and oxidized dichlorofluorescein both in skeletal muscle tissue and erythrocytes preparations, and PRP treatment significantly reduced these oxidative damage markers. Furthermore, the contusion decreased the cellular viability in the site of the lesion and PRP was effective in diminishing this effect. Moreover, PRP increased the levels of enzymatic antioxidants superoxide dismutase and catalase activities in the injured muscle, and also the non-protein thiols (-SH) group levels in erythrocytes. In conclusion PRP, in the form that was used in this study, was able to modulate the oxidative damage determined by a classical skeletal muscle injury possibly by reducing the impairment of myocytes mitochondrial function and improving their endogenous antioxidant defense systems. PMID- 27255145 TI - Improving the Medication Reconciliation Discharge Prescription Documentation of Rationale for New or Changed Medications at the Niagara Health System. PMID- 27255148 TI - Molecular dynamics simulations and CD spectroscopy reveal hydration-induced unfolding of the intrinsically disordered LEA proteins COR15A and COR15B from Arabidopsis thaliana. AB - The LEA (late embryogenesis abundant) proteins COR15A and COR15B from Arabidopsis thaliana are intrinsically disordered under fully hydrated conditions, but obtain alpha-helical structure during dehydration, which is reversible upon rehydration. To understand this unusual structural transition, both proteins were investigated by circular dichroism (CD) and molecular dynamics (MD) approaches. MD simulations showed unfolding of the proteins in water, in agreement with CD data obtained with both HIS-tagged and untagged recombinant proteins. Mainly intramolecular hydrogen bonds (H-bonds) formed by the protein backbone were replaced by H-bonds with water molecules. As COR15 proteins function in vivo as protectants in leaves partially dehydrated by freezing, unfolding was further assessed under crowded conditions. Glycerol reduced (40%) or prevented (100%) unfolding during MD simulations, in agreement with CD spectroscopy results. H-bonding analysis indicated that preferential exclusion of glycerol from the protein backbone increased stability of the folded state. PMID- 27255147 TI - 17beta-Estradiol Reverses Leptin-Inducing Ovarian Cancer Cell Migration by the PI3K/Akt Signaling Pathway. AB - Accumulating evidence suggests that leptin is expressed at higher levels in obese women and stimulates cell migration in epithelial cancers. However, the biology of ovarian cancer is different from others, mainly due to the production of estrogens because of the involvement of ovarian tissue, which is the main source of estrogens; as a result, the levels are at least 100- to 1000-fold higher than normal circulating levels. Thus, ovarian cancer tissues are exposed to 17beta estradiol, which promotes ovarian cancer cell migration and may modulate the effect of other hormones. Therefore, this study investigated the effects of 17beta-estradiol (1 nmol/L) with leptin (1-40 ng/mL) at physiological levels, on the migration of OVCAR-3 and SKOV-3 ovarian cancer cells, and the expression levels and activity of metalloproteinases (MMPs) 2 and 9. Here, we found that leptin stimulated ovarian cancer cell line migration, which is mediated via the expression and activity of MMP-9 in the OVCAR-3 but not in the SKOV-3 cells. After the administration of 17beta-estradiol and leptin, we observed antagonistic effects of 17beta-estradiol on leptin-induced OVCAR-3 cell migration and MMP-9 expression and activity. Moreover, the antagonistic effect of 17beta-estradiol on leptin-induced cancer cell migration was reversed by pretreatment of the cells with the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor. Taken together, our results, for the first time, show that in ovarian cancer cells ObR+/ER+, 17beta-estradiol has an antagonistic effect on leptin-induced cell migration as well as MMP-9 expression and activity, which is mediated by the PI3K pathway. PMID- 27255149 TI - Pertussis Antibody Concentrations in Infants Born Prematurely to Mothers Vaccinated in Pregnancy. AB - BACKGROUND AND OBJECTIVES: Maternal antenatal pertussis-containing vaccination is recommended for the prevention of neonatal pertussis, but the ability of maternal vaccination to protect premature infants is unknown. We hypothesized that that infants born prematurely to antenatally vaccinated women would have higher pertussis antibody concentrations than those born to unvaccinated women. METHODS: Mothers had been offered a combined tetanus, diphtheria, 5-component acellular pertussis, inactivated polio vaccine from 28 weeks' gestation as part of their routine antenatal care. Premature infants of vaccinated and unvaccinated mothers enrolled in a randomized controlled trial of pneumococcal conjugate vaccine schedules had antibody concentrations (pertussis toxin, filamentous hemoagglutinin [FHA], and fimbriae 2 and 3) measured at 2 months (before primary vaccination), 5 months (1 month after primary vaccination), and 12 months of age. RESULTS: Mothers of 31 (19%) of 160 premature infants had received combined tetanus, diphtheria, 5-component acellular pertussis, inactivated polio vaccine in pregnancy. Compared with infants of unvaccinated mothers, those born to vaccinated mothers had significantly higher antibody concentrations at 2 months for all measured vaccine antigens (P < .001). The number of days between maternal vaccination and delivery and immunoglobulin G concentration at 2 months of age was positively correlated for pertussis toxin (P = .011) and FHA (P = .001). After primary immunization, infants of vaccinated mothers had significantly lower antibody concentrations for FHA (P = .003) compared with infants of unvaccinated mothers; these differences had resolved by 12 months of age. CONCLUSIONS: Maternal vaccination administered early in the third trimester may provide protection for infants born prematurely. PMID- 27255150 TI - Congenital Trismus From Brainstem Dysgenesis: Case Report and Review of Literature. AB - Trismus refers to any condition inducing limited mouth opening and may present as a result of acquired or congenital pathology. We present the case of a newborn who presented with severe, congenital trismus due to brainstem dysgenesis. We describe the course of his investigations, and a multidisciplinary approach to the management of his care and follow-up. To our knowledge, this is one of the earliest reported cases of congenital trismus attributable to brainstem dysgenesis. A literature review was conducted to provide an overview of the differential pathogenesis as it presents in congenital cases and discuss the complexity of managing congenital trismus due to brainstem dysgenesis in a neonate and infant. PMID- 27255151 TI - Two-Step Process for ED UTI Screening in Febrile Young Children: Reducing Catheterization Rates. AB - BACKGROUND AND OBJECTIVES: Urinary tract infection (UTI) screening in febrile young children can be painful and time consuming. We implemented a screening protocol for UTI in a high-volume pediatric emergency department (ED) to reduce urethral catheterization, limiting catheterization to children with positive screens from urine bag specimens. METHODS: This quality-improvement initiative was implemented using 3 Plan-Do-Study-Act cycles, beginning with a small test of the proposed change in 1 ED area. To ensure appropriate patients received timely screening, care teams discussed patient risk factors and created patient specific, appropriate procedures. The intervention was extended to the entire ED after providing education. Finally, visual cues were added into the electronic health record, and nursing scripts were developed to enlist family participation. A time-series design was used to study the impact of the 6-month intervention by using a p-chart to determine special cause variation. The primary outcome measure for the study was defined as the catheterization rate in febrile children ages 6 to 24 months. RESULTS: The ED reduced catheterization rates among febrile young children from 63% to <30% over a 6-month period with sustained results. More than 350 patients were spared catheterization without prolonging ED length of stay. Additionally, there was no change in the revisit rate or missed UTIs among those followed within the hospital's network. CONCLUSIONS: A 2-step less-invasive process for screening febrile young children for UTI can be instituted in a high volume ED without increasing length of stay or missing cases of UTI. PMID- 27255152 TI - The association of serum long-chain n-3 PUFA and hair mercury with exercise cardiac power in men. AB - Long-chain n-3 PUFA from fish and exercise capacity are associated with CVD risk. Fish, especially large and old predatory fish, may contain Hg, which may attenuate the inverse association of long-chain n-3 PUFA with CVD. However, the associations of long-chain n-3 PUFA or Hg exposure with exercise capacity are not well known. We aimed to evaluate the associations of serum long-chain n-3 PUFA EPA, docosapentaenoic acid (DPA) and DHA and hair Hg with exercise cardiac power (ECP, a ratio of VO2max:maximal systolic blood pressure (SBP) during an exercise test), a measure for exercise capacity. For this, data from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were analysed cross-sectionally in order to determine the associations between serum long-chain n-3 PUFA, hair Hg and ECP in 1672 men without CVD, aged 42-60 years. After multivariate adjustments, serum total long-chain n-3 PUFA concentration was associated with higher ECP and VO2max (P trend across quartiles=0.04 and P trend=0.02, respectively), but not with maximal SBP (P trend=0.69). Associations were generally similar when EPA, DPA and DHA were evaluated individually. Hair Hg was not associated with ECP, VO2max or maximal SBP. However, the associations of total long-chain n-3 PUFA (P interaction=0.03) and EPA (P interaction=0.02) with higher VO2max were stronger among men with lower hair Hg. Higher serum long-chain n-3 PUFA concentration, mainly a marker for fish consumption in this study population, was associated with higher ECP and VO2max in middle-aged men from eastern Finland. PMID- 27255153 TI - Adhesive organ regeneration in Macrostomum lignano. AB - BACKGROUND: Flatworms possess pluripotent stem cells that can give rise to all cell types, which allows them to restore lost body parts after injury or amputation. This makes flatworms excellent model systems for studying regeneration. In this study, we present the adhesive organs of a marine flatworm as a simple model system for organ regeneration. Macrostomum lignano has approximately 130 adhesive organs at the ventral side of its tail plate. One adhesive organ consists of three interacting cells: one adhesive gland cell, one releasing gland cell, and one modified epidermal cell, called an anchor cell. However, no specific markers for these cell types were available to study the regeneration of adhesive organs. RESULTS: We tested 15 commercially available lectins for their ability to label adhesive organs and found one lectin (peanut agglutinin) to be specific to adhesive gland cells. We visualized the morphology of regenerating adhesive organs using lectin- and antibody staining as well as transmission electron microscopy. Our findings indicate that the two gland cells differentiate earlier than the connected anchor cells. Using EdU/lectin staining of partially amputated adhesive organs, we showed that their regeneration can proceed in two ways. First, adhesive gland cell bodies are able to survive partial amputation and reconnect with newly formed anchor cells. Second, adhesive gland cell bodies are cleared away, and the entire adhesive organ is build anew. CONCLUSION: Our results provide the first insights into adhesive organ regeneration and describe ten new markers for differentiated cells and tissues in M. lignano. The position of adhesive organ cells within the blastema and their chronological differentiation have been shown for the first time. M. lignano can regenerate adhesive organs de novo but also replace individual anchor cells in an injured organ. Our findings contribute to a better understanding of organogenesis in flatworms and enable further molecular investigations of cell-fate decisions during regeneration. PMID- 27255154 TI - A rare case of IgG4-related disease: a gastric mass, associated with regional lymphadenopathy. AB - BACKGROUND: IgG4-related disease (IgG4-RD) is a newly recognized disorder, characterized by massive IgG4+ lymphocyte and plasma cell infiltration, storiform fibrosis, causing enlargement, nodules or thickening of the various organs, simultaneously or metachronously. Involvement of the gastrointestinal tract is very rare and can be presented as a diffuse wall thickening or polyp or mass-like lesion. Up to now, there have been reported only a few cases of isolated gastric IgG4-RD. CASE PRESENTATION: We present an unusual case of IgG4-RD of the stomach with involvement of the regional lymph nodes, clinically manifested as a gastric cancer with related pyloric stenosis. The patient underwent distal gastrectomy, omentectomy and lymph node dissection. The postoperative serum IgG4 level was increased. The diagnosis was confirmed by immunohistochemical study. CONCLUSIONS: In the most of the reported cases there was not sufficient data about the regional lymph nodal status, although the majority of the patients had been operated with presumptive diagnosis of gastric neoplasm. Our case is rare and valuable because it presents a gastric IgG4-related lesion larger than all previously reported in literature, and IgG4-related lymphadenopathy, confirmed histologically, which contributes to better knowledge of the disease. PMID- 27255155 TI - Determinants of stillbirths in Ghana: does quality of antenatal care matter? AB - BACKGROUND: Each year, over two million babies die before they are born. Like maternal deaths, the great majority of these stillbirths occur in developing countries, with about a third of all cases worldwide in sub-Saharan Africa (SSA). Few studies have, however, examined the determinants of stillbirths in SSA. In addition, the emphases on promoting deliveries by skilled birth attendants and/or in health facilities to prevent maternal deaths, though important, may have undermined efforts to provide good quality antenatal care (ANC), which may have an additional role in preventing stillbirths. This study examines the factors associated with stillbirths in Ghana, focusing on the role of ANC quality. METHODS: Data are from the Ghana Maternal Health Survey (N = 4,868)-a national survey of women of reproductive age. The main analysis includes women who had a pregnancy ending in a live birth or stillbirth in the five years preceding the survey and who received ANC at least once. ANC quality is measured by an index based on receipt (or otherwise) of nine antenatal services during the last pregnancy, including education about pregnancy complications; with receipt of at least of eight services classified as higher quality ANC. Stillbirths refer to babies born dead at seven or more months of pregnancy. Analytic techniques include multilevel logistic regression, with moderation and mediation analysis to examine conditional and intervening effects respectively. RESULTS: Higher quality ANC decreases the odds of a stillbirth by almost half after accounting for other factors, including the type of delivery provider and facility. Educating pregnant women about pregnancy complications contributes significantly to this difference by ANC quality. The type of delivery facility and provider account for a small proportion (14 %) of the ANC quality effect on stillbirths and a larger proportion of the rural/urban difference (27 %) in stillbirths. Completing the recommended four antenatal visits decreases the odds of a stillbirth. Having a pregnancy complication, a multiple gestation, a past stillbirth, or a sister who died from pregnancy complications increases the odds of a stillbirth. CONCLUSIONS: Good quality ANC can improve birth outcomes in two ways: directly through preventative measures, and indirectly through promoting deliveries in health facilities where complications can be better managed. Targeted programs and policies to increase ANC quality, including adequately educating women on pregnancy complications, will help improve birth outcomes in Ghana, and in SSA as a whole. PMID- 27255156 TI - Task-specific ankle robotics gait training after stroke: a randomized pilot study. AB - BACKGROUND: An unsettled question in the use of robotics for post-stroke gait rehabilitation is whether task-specific locomotor training is more effective than targeting individual joint impairments to improve walking function. The paretic ankle is implicated in gait instability and fall risk, but is difficult to therapeutically isolate and refractory to recovery. We hypothesize that in chronic stroke, treadmill-integrated ankle robotics training is more effective to improve gait function than robotics focused on paretic ankle impairments. FINDINGS: Participants with chronic hemiparetic gait were randomized to either six weeks of treadmill-integrated ankle robotics (n = 14) or dose-matched seated ankle robotics (n = 12) videogame training. Selected gait measures were collected at baseline, post-training, and six-week retention. Friedman, and Wilcoxon Sign Rank and Fisher's exact tests evaluated within and between group differences across time, respectively. Six weeks post-training, treadmill robotics proved more effective than seated robotics to increase walking velocity, paretic single support, paretic push-off impulse, and active dorsiflexion range of motion. Treadmill robotics durably improved gait dorsiflexion swing angle leading 6/7 initially requiring ankle braces to self-discarded them, while their unassisted paretic heel-first contacts increased from 44 % to 99.6 %, versus no change in assistive device usage (0/9) following seated robotics. CONCLUSIONS: Treadmill integrated, but not seated ankle robotics training, durably improves gait biomechanics, reversing foot drop, restoring walking propulsion, and establishing safer foot landing in chronic stroke that may reduce reliance on assistive devices. These findings support a task-specific approach integrating adaptive ankle robotics with locomotor training to optimize mobility recovery. CLINICAL TRIAL IDENTIFIER: NCT01337960. https://clinicaltrials.gov/ct2/show/NCT01337960?term=NCT01337960&rank=1. PMID- 27255157 TI - Dabrafenib in an elderly patient with metastatic melanoma and BRAF V600R mutation: a case report. AB - BACKGROUND: Approximately 50 % of malignant melanomas harbor activating point mutations in the BRAF gene. Typically, these mutations result in the substitution of the amino acid valine at codon 600 of the gene, and 90-95 % of mutations are either BRAF (V600E) or BRAF (V600K). Specific BRAF inhibitors such as dabrafenib and vemurafenib are the mainstays of treatment in patients with metastatic BRAF mutant malignant melanomas. The third most common BRAF mutation is V600R, which also leads to increased BRAF signaling. Although evidence exists about the activity of dabrafenib and vemurafenib in patients with the BRAF (V600R) mutation, these patients have been systematically excluded from recent trials with targeted therapies. CASE PRESENTATION: Here, we report the positive results in terms of survival and quality of life obtained with dabrafenib in an 80-year old Caucasian male patient with a Charlson Comorbidity Index of 8 diagnosed with metastatic malignant melanoma harboring the BRAF (V600R) mutation. Our patient was treated with dabrafenib for 7 months with minimal toxicity. We also report exploratory analyses of circulating tumor DNA during targeted treatment. Interestingly, the mutation was not detected after starting treatment and became detectable before radiological disease progression. CONCLUSIONS: Our report suggests that (1) a relevant benefit can be obtained with a BRAF inhibitor in real-world patients with a malignant melanoma harboring a BRAF (V600R) mutation, and that (2) circulating tumor DNA detection might be of help in assessing tumor burden in everyday clinical practice. The results reported here should encourage the inclusion of patients with BRAF (V600R)-mutated malignant melanomas in future prospective clinical trials with BRAF inhibitors. PMID- 27255158 TI - Serum zinc concentrations and depression in persons with Human Immunodeficiency Virus infection: The positive living with HIV (POLH) study. AB - Low levels of serum zinc concentrations and depression are common in persons infected with Human Immunodeficiency Virus (HIV). Low levels of serum zinc concentrations may increase risk of depression in general population. However, research on the role of zinc in depression among HIV- infected person is limited. We assessed the association between serum zinc concentrations and depression in HIV-infected persons. A cross-sectional survey was conducted among 311 HIV positive people (177 men and 134 women) aged 18-60 years residing in Kathmandu, Nepal. The atomic absorption method was used to measure serum zinc concentrations and the Beck Depression Inventory (BDI)-Ia method was used to measure depression, with cut off score 20 or higher consistent with clinically significant depression. Relationships were assessed using multiple linear and logistic regression analyses. Serum zinc concentrations were significantly inversely associated with depression in all participants and in men but not in women. Participants with the highest tertile of serum zinc concentrations had a significantly decreased risk of depression in men but not in women. Serum zinc concentrations were inversely associated with depressive symptoms scores in HIV infected men. Further prospective studies are needed to confirm the role of zinc in depression among persons infected with HIV. PMID- 27255159 TI - Flexible endoscopic Zenker's diverticulotomy toolbox. PMID- 27255160 TI - An analysis of the origin of an early medieval group of individuals from Grodek based on the analysis of stable oxygen isotopes. AB - In the early Middle Ages, the region of the Cherven Towns, which is now located on both sides of the Polish-Ukrainian border, was fiercely contested by Slavs in the process of forming their early states. The main objective of the present study was to investigate the homogeneity of an early medieval population uncovered in that region, in the town of Grodek on the Bug River, by screening for non-local individuals. The origin of the studied skeletons was ascertained using analysis of oxygen isotopes in the phosphates isolated from bone tissue. In this paper, the isotope ratios obtained for samples collected from 62 human skeletons were compared to the background delta(18)O (in precipitation water) from the regions of Krakow (south-eastern Poland), Lviv (western Ukraine), Brest (western Belarus), and Grodek, as well as to the ratios determined for the animals coexisting with the studied population. Proportions of oxygen isotopes obtained for all the studied individuals were found to be similar to those for the precipitation water and animals, which indicates the absence of bone fragments of individuals originating in other regions. PMID- 27255161 TI - A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for beta-catenin. AB - Cell-cell adhesion is central to morphogenesis and maintenance of epithelial cell state. We previously identified 27 candidate cell-cell adhesion regulatory proteins (CCARPs) whose down-regulation disrupts epithelial cell-cell adhesion during collective migration. Using a protein interaction mapping strategy, we found that 18 CCARPs link to core components of adherens junctions or desmosomes. We further mapped linkages between the CCARPs and other known cell-cell adhesion proteins, including hits from recent screens uncovering novel components of E cadherin adhesions. Mechanistic studies of one novel CCARP which links to multiple cell-cell adhesion proteins, the phosphatase DUSP23, revealed that it promotes dephosphorylation of beta-catenin at Tyr 142 and enhances the interaction between alpha- and beta-catenin. DUSP23 knockdown specifically diminished adhesion to E-cadherin without altering adhesion to fibronectin matrix proteins. Furthermore, DUSP23 knockdown produced "zipper-like" cell-cell adhesions, caused defects in transmission of polarization cues, and reduced coordination during collective migration. Thus, this study identifies multiple novel connections between proteins that regulate cell-cell interactions and provides evidence for a previously unrecognized role for DUSP23 in regulating E cadherin adherens junctions through promoting the dephosphorylation of beta catenin. PMID- 27255162 TI - Genomic profiling of malignant phyllodes tumors reveals aberrations in FGFR1 and PI-3 kinase/RAS signaling pathways and provides insights into intratumoral heterogeneity. AB - Malignant phyllodes tumors of the breast are poorly understood rare neoplasms with potential for aggressive behavior. Few efficacious treatment options exist for progressed or metastatic disease. The molecular features of malignant phyllodes tumors are poorly defined, and a deeper understanding of the genetics of these tumors may shed light on pathogenesis and progression and potentially identify novel treatment approaches. We sequenced 510 cancer-related genes in 10 malignant phyllodes tumors, including 5 tumors with liposarcomatous differentiation and 1 with myxoid chondrosarcoma-like differentiation. Intratumoral heterogeneity was assessed by sequencing two separate areas in 7 tumors, including non-heterologous and heterologous components of tumors with heterologous differentiation. Activating hotspot mutations in FGFR1 were identified in 2 tumors. Additional recurrently mutated genes included TERT promoter (6/10), TP53 (4/10), PIK3CA (3/10), MED12 (3/10), SETD2 (2/10) and KMT2D (2/10). Together, genomic aberrations in FGFR/EGFR PI-3 kinase and RAS pathways were identified in 8 (80%) tumors and included mutually exclusive and potentially actionable activating FGFR1, PIK3CA and BRAF V600E mutations, inactivating TSC2 mutation, EGFR amplification and PTEN loss. Seven (70%) malignant phyllodes tumors harbored TERT aberrations (six promoter mutations, one amplification). For comparison, TERT promoter mutations were identified by Sanger sequencing in 33% borderline (n=12) and no (0%, n=8) benign phyllodes tumors (P=0.391 and P=0.013 vs malignant tumors, respectively). Genetic features specific to liposarcoma, including CDK4/MDM2 amplification, were not identified. Copy number analysis revealed intratumoral heterogeneity and evidence for divergent tumor evolution in malignant phyllodes tumors with and without heterologous differentiation. Tumors with liposarcomatous differentiation revealed more chromosomal aberrations in non heterologous components compared with liposarcomatous components. EGFR amplification was heterogeneous and present only in the non-heterologous component of one tumor with liposarcomatous differentiation. The results identify novel pathways involved in the pathogenesis of malignant phyllodes tumors, which significantly increase our understanding of tumor biology and have potential clinical impact. PMID- 27255163 TI - Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria. AB - Previously, our international team proposed a three-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification-A tumors have well-demarcated glands lacking destructive stromal invasion or lymphovascular invasion, Pattern Classification-B tumors show localized, limited destructive invasion arising from A-type glands, and Pattern Classification-C tumors have diffuse destructive stromal invasion, significant (filling a 4 * field) confluence, or solid architecture. Twenty-four cases of Pattern Classification-A, 22 Pattern Classification-B, and 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis originally established. One H&E slide per case was reviewed by seven gynecologic pathologists, four from the original study. Kappa statistics were prepared, and cases with discrepancies reviewed. We found a majority agreement with reference diagnosis in 81% of cases, with complete or near complete (six of seven) agreement in 50%. Overall concordance was 74%. Overall kappa (agreement among pathologists) was 0.488 (moderate agreement). Pattern Classification-B has lowest kappa, and agreement was not improved by combining B+C. Six of seven reviewers had substantial agreement by weighted kappas (>0.6), with one reviewer accounting for the majority of cases under or overcalled by two tiers. Confluence filling a 4 * field, labyrinthine glands, or solid architecture accounted for undercalling other reference diagnosis-C cases. Missing a few individually infiltrative cells was the most common cause of undercalling reference diagnosis-B. Small foci of inflamed, loose or desmoplastic stroma lacking infiltrative tumor cells in reference diagnosis-A appeared to account for those cases up-graded to Pattern Classification-B. In summary, an overall concordance of 74% indicates that the criteria can be reproducibly applied by gynecologic pathologists. Further refinement of criteria should allow use of this powerful classification system to delineate which cervical adenocarcinomas can be safely treated conservatively. PMID- 27255165 TI - Significance of myelodysplastic syndrome-associated somatic variants in the evaluation of patients with pancytopenia and idiopathic cytopenias of undetermined significance. AB - In this study, we set out to evaluate the frequency of mutations in 20 myelodysplastic syndrome-associated genes in 53 individuals with pancytopenia in which bone marrow evaluation failed to meet standard criteria for a diagnosis of myelodysplastic syndrome. These idiopathic pancytopenia cases were associated with no specific cause for their pancytopenia (n=28), aplastic anemia (n=13), pancytopenia attributable to liver disease (n=4), pancytopenia associated with autoimmune disease (n=4), and pancytopenia attributed to drug effect (n=4). We also selected 38 bone marrow aspirates from patients presenting with pancytopenia and meeting criteria for a diagnosis of myelodysplastic syndrome (n=21) or acute myeloid leukemia (n=17) as malignant comparison cases. Targeted sequencing of the 20 genes was performed on all cases. The idiopathic pancytopenia group had a lower average age (46 vs 66 years, P<0.0001) and a lower number of mutations per case that were statistically significant (0.81 vs 1.18, P=0.045). The frequency of cases with at least one mutation was higher for cases with a diagnosable myeloid neoplasm (68 vs 38%, P=0.012). Except for mutations in U2AF1, which was mutated in 5 of the 38 malignant cases (13.2%) and in none of the idiopathic pancytopenia cases (P=0.011), the frequency of mutations in the genes evaluated was not significantly different between idiopathic pancytopenia and malignant cases. Median and mean clinical follow-up for the idiopathic pancytopenia group was available for 444 and 739 days, respectively. Over this time frame, none of the idiopathic pancytopenia patients was diagnosed with a myelodysplastic syndrome or an acute myeloid leukemia. These findings provide further evidence that identification of mutations in several genes associated with myelodysplastic syndromes should not be used alone to support a diagnosis of a myelodysplastic syndrome. PMID- 27255164 TI - Genomewide copy number analysis of Mullerian adenosarcoma identified chromosomal instability in the aggressive subgroup. AB - Mullerian adenosarcomas are malignant gynecologic neoplasms. Advanced staging and sarcomatous overgrowth predict poor prognosis. Because the genomic landscape remains poorly understood, we conducted this study to characterize the genomewide copy number variations in adenosarcomas. Sixteen tumors, including eight with and eight without sarcomatous overgrowth, were subjected to a molecular inversion probe array analysis. Copy number variations, particularly losses, were significantly higher in cases with sarcomatous overgrowth. Frequent gains of chromosomal 12q were noted, often involving cancer-associated genes CDK4 (six cases), MDM2, CPM, YEATS4, DDIT3, GLI1 (five each), HMGA2 and STAT6 (four), without association with sarcomatous overgrowth status. The most frequent losses involved chromosomes 13q (five cases), 9p, 16q and 17q (four cases each) and were almost limited to cases with sarcomatous overgrowth. MDM2 and CDK4 amplification, as well as losses of RB1 (observed in two cases) and CDKN2A/B (one case), was verified by FISH. By immunohistochemistry, all MDM2/CDK4-coamplified cases were confirmed to overexpress both encoded proteins, whereas all four cases with (plus an additional four without) gain of HMGA2 overexpressed the HMGA2 protein. Both cases with RB1 loss were negative for the immunostaining of the encoded protein. Chromothripsis-like copy number profiles involving chromosome 12 or 14 were observed in three fatal cases, all of which harbored sarcomatous overgrowth. With whole chromosome painting and deconvolution fluorescent microscopy, dividing tumor cells in all three cases were shown to have scattered extrachromosomal materials derived from chromosomes involved by chromothripsis, suggesting that this phenomenon may serve as visual evidence for chromothripsis in paraffin tissue. In conclusion, we identified frequent chromosome 12q amplifications, including loci containing potential pharmacological targets. Global chromosomal instability and chromothripsis were more frequent in cases with sarcomatous overgrowth. To our knowledge, this is the first time that evidence of chromothripsis has been demonstrated in paraffin-embedded clinical tissues and in adenosarcomas. PMID- 27255166 TI - [Long-term prognosis of idiopathic chronic adult hydrocephalus: I. The University Hospital Marques de Valdecilla diagnostic and therapeutic protocol]. AB - INTRODUCTION: Despite the existence of published guidelines for more than a decade, there is still a substantial variation in the management of idiopathic normal pressure hydrocephalus due to its diagnostic and therapeutic complexity. DEVELOPMENT: The diagnostic and therapeutic protocol for the management of idiopathic normal pressure hydrocephalus in use at the Department of Neurosurgery of the University Hospital Marques de Valdecilla is presented. The diagnostic process includes neuropsychological testing, phase contrast cine MRI, urodynamic evaluation, continuous intracranial pressure monitoring, cerebrospinal fluid hydrodynamics by means of lumbar infusion testing, and intra-abdominal pressure measurement. A patient is considered a surgical candidate if any of the following criteria is met: mean intracranial pressure >15mmHg, or B-waves present in >10% of overnight recording; pressure-volume index <15ml, or resistance to cerebrospinal fluid outflow (ROUT) >4.5mmHg/ml/min in bolus infusion test; ROUT >12mmHg/ml/min, intracranial pressure >22mmHg, or high amplitude B-waves in the steady-state of the continuous rate infusion test; or a clinical response to high volume cerebrospinal fluid withdrawal. CONCLUSIONS: The implementation of a diagnostic and therapeutic protocol for idiopathic normal pressure hydrocephalus management could improve various aspects of patient care. It could reduce variability in clinical practice, optimise the use of health resources, and help in identifying scientific uncertainty areas, in order to direct research efforts in a more appropriate way. PMID- 27255167 TI - The RooPfs study to assess whether improved housing provides additional protection against clinical malaria over current best practice in The Gambia: study protocol for a randomized controlled study and ancillary studies. AB - BACKGROUND: In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. This study will determine if modern housing provides incremental protection against clinical malaria over the current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in The Gambia, determine the incremental cost-effectiveness of the interventions, and analyze the housing market in The Gambia. METHODS/DESIGN: A two-armed, household, cluster-randomized, controlled study will be conducted to assess whether improved housing and LLINs combine to provide better protection against clinical malaria in children than LLINs alone in The Gambia. The unit of randomization will be the household, defined as a house and its occupants. A total of 800 households will be enrolled and will receive LLINs, and 400 will receive improved housing before clinical follow-up. One child aged 6 months to 13 years will be enrolled from each household and followed for clinical malaria using active case detection to estimate malaria incidence for two malaria transmission seasons. Episodes of clinical malaria will be the primary endpoint. Study children will be surveyed at the end of each transmission season to estimate the prevalence of Plasmodium falciparum infection, parasite density, and the prevalence of anemia. Exposure to malaria parasites will be assessed using light traps, followed by detection of Anopheles gambiae species and sporozoite infection. Ancillary economic and social science studies will undertake a cost effectiveness analysis and use qualitative and participatory methods to explore the acceptability of the housing modifications and to design strategies for scaling-up housing interventions. DISCUSSION: The study is the first of its kind to measure the efficacy of housing on reducing clinical malaria, assess the incremental cost-effectiveness of improved housing, and identify mechanisms for scaling up housing interventions. Trial findings will help inform policy makers on improved housing for malaria control in sub-Saharan Africa. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN02622179 . Registered on 23 September 2014. PMID- 27255168 TI - Diastolic orthostatic hypertension and cardiovascular prognosis in type 2 diabetes: a prospective cohort study. AB - BACKGROUND: In patients with type 2 diabetes, the prognostic impact of an orthostatic rise in blood pressure is not known. Therefore, the aim of this study was to determine the prognostic implications of the diastolic orthostatic blood pressure response in a cohort of patients with type 2 diabetes. We also evaluated associations between different orthostatic blood pressure responses and markers of subclinical cardiovascular organ damage. METHODS: Office blood pressures were measured in the sitting and in the standing position in 749 patients with type 2 diabetes who participated in the CARDIPP study (Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care). Diastolic orthostatic hypertension was defined as a rise of diastolic blood pressure >=10 mmHg and diastolic orthostatic hypotension was defined as a drop of diastolic blood pressure >=10 mmHg. Recruitment took place between the years 2005-2008, and patients were followed until any of the primary outcome events (cardiovascular death or hospitalization for either myocardial infarction or stroke) occurred or until December 31st, 2014. Measurements of aortic pulse wave velocity and of carotid intima-media thickness were performed at base-line. RESULTS: Diastolic orthostatic hypertension was found in 140 patients (18.7 %) and was associated with significantly lower risk of cardiovascular events (crude hazard ratio compared with patients with normal systolic and diastolic orthostatic blood pressure response: 0.450, 95 % C.I. 0.206-0.987, P = 0.046). Diastolic orthostatic hypotension was found in 31 patients (4.1 %) and was associated with higher values for aortic pulse wave velocity and carotid intima-media thickness, compared with patients with normal systolic and diastolic orthostatic blood pressure response. CONCLUSIONS: Diastolic orthostatic hypertension is common in patients with type 2 diabetes, and may be a novel marker for decreased cardiovascular risk in these patients. PMID- 27255169 TI - A screen for constituents of motor control and decision making in Drosophila reveals visual distance-estimation neurons. AB - Climbing over chasms larger than step size is vital to fruit flies, since foraging and mating are achieved while walking. Flies avoid futile climbing attempts by processing parallax-motion vision to estimate gap width. To identify neuronal substrates of climbing control, we screened a large collection of fly lines with temporarily inactivated neuronal populations in a novel high throughput assay described here. The observed climbing phenotypes were classified; lines in each group are reported. Selected lines were further analysed by high-resolution video cinematography. One striking class of flies attempts to climb chasms of unsurmountable width; expression analysis guided us to C2 optic-lobe interneurons. Inactivation of C2 or the closely related C3 neurons with highly specific intersectional driver lines consistently reproduced hyperactive climbing whereas strong or weak artificial depolarization of C2/C3 neurons strongly or mildly decreased climbing frequency. Contrast-manipulation experiments support our conclusion that C2/C3 neurons are part of the distance evaluation system. PMID- 27255170 TI - Triple-site pacing for cardiac resynchronization in permanent atrial fibrillation - Acute phase results from a prospective observational study. AB - INTRODUCTION AND AIM: Multi-site pacing is emerging as a new method for improving response to cardiac resynchronization therapy (CRT), but has been little studied, especially in patients with atrial fibrillation. We aimed to assess the effects of triple-site (Tri-V) vs. biventricular (Bi-V) pacing on hemodynamics and QRS duration. METHODS: This was a prospective observational study of patients with permanent atrial fibrillation and ejection fraction <40% undergoing CRT implantation (n=40). One right ventricular (RV) lead was implanted in the apex and another in the right ventricular outflow tract (RVOT) septal wall. A left ventricular (LV) lead was implanted in a conventional venous epicardial position. Cardiac output (using the FloTracTM VigileoTM system), mean QRS and ejection fraction were calculated. RESULTS: Mean cardiac output was 4.81+/-0.97 l/min with Tri-V, 4.68+/-0.94 l/min with RVOT septal and LV pacing, and 4.68+/-0.94 l/min with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV). Mean pre implantation QRS was 170+/-25 ms, 123+/-18 ms with Tri-V, 141+/-25 ms with RVOT septal pacing and LV pacing and 145+/-19 with RV apical and LV pacing (p<0.001 for Tri-V vs. both BiV and pre-implantation). Mean ejection fraction was significantly higher with Tri-V (30+/-11%) vs. Bi-V pacing (28+/-12% with RVOT septal and LV pacing and 28+/-11 with RV apical and LV pacing) and pre implantation (25+/-8%). CONCLUSION: Tri-V pacing produced higher cardiac output and shorter QRS duration than Bi-V pacing. This may have a significant impact on the future of CRT. PMID- 27255171 TI - External validation of the ProACS score for risk stratification of patients with acute coronary syndromes. AB - INTRODUCTION: The ProACS risk score is an early and simple risk stratification score developed for all-cause in-hospital mortality in acute coronary syndromes (ACS) from a Portuguese nationwide ACS registry. Our center only recently participated in the registry and was not included in the cohort used for developing the score. Our objective was to perform an external validation of this risk score for short- and long-term follow-up. METHODS: Consecutive patients admitted to our center with ACS were included. Demographic and admission characteristics, as well as treatment and outcome data were collected. The ProACS risk score variables are age (>=72 years), systolic blood pressure (<=116 mmHg), Killip class (2/3 or 4) and ST-segment elevation. We calculated ProACS, Global Registry of Acute Coronary Events (GRACE) and Canada Acute Coronary Syndrome risk score (C-ACS) risk scores for each patient. RESULTS: A total of 3170 patients were included, with a mean age of 64+/-13 years, 62% with ST-segment elevation myocardial infarction. All-cause in-hospital mortality was 5.7% and 10.3% at one year follow-up. The ProACS risk score showed good discriminative ability for all considered outcomes (area under the receiver operating characteristic curve >0.75) and a good fit, similar to C-ACS, but lower than the GRACE risk score and slightly lower than in the original development cohort. The ProACS risk score provided good differentiation between patients at low, intermediate and high mortality risk in both short- and long-term follow-up (p<0.001 for all comparisons). CONCLUSIONS: The ProACS score is valid in external cohorts for risk stratification for ACS. It can be applied very early, at the first medical contact, but should subsequently be complemented by the GRACE risk score. PMID- 27255172 TI - Cardiac device infection: Review based in the experience of a single center. AB - INTRODUCTION: The incidence of cardiac implantable electronic device infections has increased significantly over the years and they are associated with significant morbidity and mortality. The epidemiology in the Central region of Portugal is not known. OBJECTIVE AND METHODS: To characterize cardiac implantable electronic device infections through a retrospective study of 3158 patients admitted to our center between January 2008 and September 2014 and to review the subject in the light of the current state of the art. RESULTS: The infection rate was 1.48% (pacemakers 1.21%, cardiac defibrillator/resynchronization devices 5.40%). The study population consisted of 47 patients with a mean age of 65+/-19 years, predominantly male (72.3%). Infections were mainly of pacemakers, the main device implanted in our population (n=2954), and most occurred late after first implantation. Clinically, most patients presented with fever and local inflammation. Blood cultures identified mainly Gram-positive microorganisms. Empiric antibiotic therapy with vancomycin was instituted in all patients, associated with gentamicin in 57%. The device was extracted in the majority of cases (72%). During follow-up (32+/-22 months) eight patients died (17%), seven of cardiovascular cause (15%), and seven were readmitted with device infection (15%). CONCLUSIONS: Our rate of infection was low, similar to other published series, with a higher rate in cardiac defibrillator/resynchronization devices. After standard treatment with antibiotic therapy and device extraction, the prognosis was good. PMID- 27255173 TI - Cardiotoxicity in anthracycline therapy: Prevention strategies. AB - The increasing use of anthracyclines, together with the longer survival of cancer patients, means the toxic effects of these drugs need to be monitored. In order to detect, prevent or mitigate anthracycline-induced cardiomyopathy, it is essential that all patients undergo a rigorous initial cardiovascular assessment, followed by close monitoring. Several clinical trials have shown the cardioprotective effect of non-pharmacological measures such as exercise, healthy lifestyles, control of risk factors and treatment of comorbidities; a cardioprotective effect has also been observed with pharmacological measures such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, statins, dexrazoxane and liposomal formulations. However, there are currently no guidelines for managing prevention in these patients. In this review the authors discuss the state of the art of the assessment, monitoring, and, above all, the prevention of anthracycline-induced cardiotoxicity. PMID- 27255174 TI - The arterial baroreflex effectiveness index in risk stratification of chronic heart failure patients who are candidates for cardiac resynchronization therapy. AB - INTRODUCTION: Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT. METHODS: The study population consisted of 25 patients with indication for CRT, aged 65+/-10 years, NYHA functional class >=III in 52%, QRS width 159+/-15 ms, left ventricular ejection fraction (LVEF) 29+/-5%, left ventricular end-systolic volume (LVESV) 150+/-48 ml, B-type natriuretic peptide (BNP) 357+/-270 pg/ml, and peak oxygen consumption (peak VO2) 18.4+/-5.0 ml/kg/min. An orthostatic tilt test was performed to assess the baroreflex effectiveness index (BEI) by the sequence method. This group was compared with 15 age-matched healthy individuals. RESULTS: HF patients showed a significantly depressed BEI during tilt (31+/-12% vs. 49+/ 18%, p=0.001). A lower BEI was associated with higher BNP (p=0.038), lower peak VO2 (p=0.048), and higher LVESV (p=0.031). By applying a cut-off value of 25% for BEI, two clusters of patients were identified: lower risk cluster (BEI >25%) QRS 153 ms, LVESV 129 ml, BNP 146 pg/ml, peak VO2 19.0 ml/kg/min; and higher risk cluster (IEB <=25%) QRS 167 ms, LVESV 189 ml, BNP 590 pg/ml, peak VO2 16.2 ml/kg/min. CONCLUSIONS: Candidates for CRT show depressed arterial baroreflex function. Lower BEI was observed in high-risk HF patients. Baroreflex function correlated closely with other clinical HF parameters. Therefore, BEI may improve risk stratification in HF patients undergoing CRT. PMID- 27255175 TI - Aortic embolization of an Edwards SAPIEN prosthesis due to sigmoid left ventricular hypertrophy: Case report. AB - Transcatheter aortic valve implantation (TAVI) is considered an alternative therapy in high-risk patients with severe aortic stenosis. Although a minimally invasive procedure, it is not free from complications, one of which is valve embolization at the time of TAVI. We present a case of embolization of a balloon expandable aortic valve due to sigmoid left ventricular hypertrophy and managed with a second valve without surgery. The embolized valve was repositioned in the aortic arch between the left common carotid artery and the brachiocephalic trunk. PMID- 27255176 TI - Development of hydroxy-based sphingosine kinase inhibitors and anti-inflammation in dextran sodium sulfate induced colitis in mice. AB - Sphingosine kinase (SphK)-catalyzed production of sphingosine-1-phosphate (S1P) regulates cell growth, survival and proliferation as well as inflammatory status in animals. In recent study we reported the N'-(3-(benzyloxy)benzylidene)-3,4,5 trihydroxybenzohydrazide scaffold as a potent SphK inhibitor. As a continuation of these efforts, 51 derivatives were synthesized and evaluated by SphK1/2 inhibitory activities for structure-activity relationship (SAR) study. Among them, 33 was identified as the most potent SphK inhibitor. Potency of 33 was also observed to efficiently decrease SphK1/2 expression in human colorectal cancer cells (HCT116) and significantly inhibit dextran sodium sulfate (DSS)-induced colitis as well as the decreased expression of interleukin (IL)-6 and cyclooxygenase-2 (COX-2) in mouse models. Collectively, 33 was validated as an effective SphK inhibitor, which can be served as anti-inflammatory agent to probably treat inflammatory bowel diseases in human. PMID- 27255177 TI - Design, synthesis, and biological evaluation of a novel series of peripheral selective noradrenaline reuptake inhibitors-Part 2. AB - Peripherally selective inhibition of noradrenaline reuptake is a novel mechanism for the treatment of stress urinary incontinence to overcome adverse effects associated with central action. Herein, we describe our medicinal chemistry approach to discover peripheral-selective noradrenaline reuptake inhibitors to avert the risk of P-gp-mediated DDI at the blood-brain barrier. We observed that steric shielding of the hydrogen-bond acceptors and donors (HBA and HBD) of compound 1 reduced the multidrug resistance protein 1 (MDR1) efflux ratio; however, the resulting compound 6, a methoxyacetamide derivative, was mainly metabolized by CYP2D6 and CYP2C19 in the in vitro phenotyping study, implying the risk of PK variability based on the genetic polymorphism of the CYPs. Replacement of the hydrogen atom with a deuterium atom in a strategic, metabolically hot spot led to compound 13, which was mainly metabolized by CYP3A4. To our knowledge, this study represents the first report of the effect of deuterium replacement for a major metabolic enzyme. The compound 13, N-{[(6S,7R)-7-(4-chloro-3 fluorophenyl)-1,4-oxazepan-6-yl]methyl}-2-[(2H(3))methyloxy]acetamide hydrochloride, which exhibited peripheral NET selective inhibition at tested doses in rats, increased urethral resistance in a dose-dependent manner. PMID- 27255178 TI - Synthesis and biological activity of pyrazole analogues of the staurosporine aglycon K252c. AB - A derivative of the staurosporine aglycon (K252c), in which the lactam ring was replaced by a pyrazole moiety, was synthesized. The resulting indolopyrazolocarbazole (3) inhibited Pim isoforms 1-3 whereas it did not impair the activity of two known targets of K252c, protein kinase C isoforms alpha and gamma. Compound 3 exhibited moderate cytotoxic activity toward human leukemia and colon carcinoma cell lines (K562 and HCT116), strongly suggesting that this new scaffold deserves further investigations for treatment of malignancies associated with Pim activity. PMID- 27255179 TI - Discovery of novel 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives as gamma-secretase modulators (Part 2). AB - gamma-Secretase modulators (GSMs), which lower pathogenic amyloid beta (Abeta) without affecting the production of total Abeta or Notch signal, have emerged as a potential therapeutic agent for Alzheimer's disease (AD). A novel series of 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine derivatives was discovered and characterized as GSMs. Optimization of substituents at the 8-position of the core scaffold using ligand-lipophilicity efficiency (LLE) as a drug-likeness guideline led to identification of various types of high-LLE GSMs. Phenoxy compound (R)-17 exhibited especially high LLE as well as potent in vivo Abeta42-lowering effect by single administration. Furthermore, multiple oral administration of (R)-17 significantly reduced soluble and insoluble brain Abeta42, and ameliorated cognitive deficit in novel object recognition test (NORT) using Tg2576 mice as an AD model. PMID- 27255180 TI - Design, synthesis, and in vitro antiproliferative and kinase inhibitory effects of pyrimidinylpyrazole derivatives terminating with arylsulfonamido or cyclic sulfamide substituents. AB - A novel series of substituted pyrimidine compounds bearing N-phenylpyrazole and terminating with aryl and cyclic sulfonamido moiety were designed, synthesized, and evaluated in vitro as antiproliferative agents against a panel of 53 cell lines of different tissues at the NCI. Among them, compound 1d with p chlorobenzenesulfonamido terminal moiety, ethylene spacer, and 4-chloro-3 methoxyphenyl ring at position 3 of the pyrazole nucleus showed the highest mean percentage inhibition value over the whole cancer cell line panel at 10 MUM concentration. It showed broad-spectrum antiproliferative activity over many cell lines of different cancer types. For instance, compound 1d inhibited the growth of HL-60 (TB), SR leukemia, and T-47D and MCF-7 breast cancer cell line by 135.92%, 119.44%, 95.32%, and 82.03% at 10 MUM, respectively. And it inhibited the growth of COLO 205 colon, HT29 colon, BT-549 breast, and ACHN renal cancer cell lines by more than 80% at the same test concentration. However, testing compound 1d upon determining its IC50 against the most sensitive cell lines showed to good extent selectivity against HT29 colon cancer cell line than HL-60 leukemia and MRC-5 lung fibroblasts (normal cells). Compound 1d was further tested against 12 kinases of different kinase families, and the highest inhibitory effect was exerted against RAF1, V600E-B-RAF, and V600K-B-RAF kinases. PMID- 27255181 TI - The first Danish family reported with an AQP5 mutation presenting diffuse non epidermolytic palmoplantar keratoderma of Bothnian type, hyperhidrosis and frequent Corynebacterium infections: a case report. AB - BACKGROUND: An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma, palmoplantar keratoderma of Bothnian type, is caused by mutations in the AQP5 gene encoding the cell-membrane water channel protein aquaporin 5 leading to defective epidermal-water-barrier function in the epidermis of the palms and soles. CASE PRESENTATION: We report the first Danish family diagnosed with diffuse non-epidermolytic palmoplantar keratoderma of Bothnian type in which fourteen individuals are potentially affected. The proband, a 36-year-old male had since childhood been affected by pronounced hyperhidrosis of the palms and soles along with palmoplantar keratoderma. He reported a very distinctive feature of the disorder, aquagenic wrinkling, as he developed pronounced maceration of the skin with translucent white papules and a spongy appearance following exposure to water. The patient presented recurrent fungal infections, a wellknown feature of the condition, but also periodic worsening with pitted keratolysis and malodour due to bacterial infections. CONCLUSIONS: Palmoplantar keratoderma of Bothnian type, which may be associated with hyperhidrosis, is frequently complicated by fungal infections and may be complicated by Corynebacterium infections. PMID- 27255182 TI - Methionine-restricted diet inhibits growth of MCF10AT1-derived mammary tumors by increasing cell cycle inhibitors in athymic nude mice. AB - BACKGROUND: Dietary methionine restriction (MR) improves healthspan in part by reducing adiposity and by increasing insulin sensitivity in rodent models. The purpose of this study was to determine whether MR inhibits tumor progression in breast cancer xenograft model and breast cancer cell lines. METHODS: Athymic nude mice were injected with MCF10AT1 cells in Matrigel(r) and fed a diet containing either 0.86 % methionine (control fed, CF), or 0.12 % methionine (MR) for 12 weeks. Plasma amino acid concentrations were measured by UPLC, and proliferation and apoptosis were examined using RT-PCR, immunohistochemistry, and Cell Titer 96(r) Aqueous One Solution Cell Proliferation assay. RESULTS: Mice on the MR diet had reduced body weight and decreased adiposity. They also had smaller tumors when compared to the mice bearing tumors on the CF diet. Plasma concentrations of the sulfur amino acids (methionine, cysteine, and taurine) were reduced, whereas ornithine, serine, and glutamate acid were increased in mice on the MR diet. MR mice exhibited decreased proliferation and increased apoptosis in cells that comprise the mammary glands and tumors of mice. Elevated expression of P21 occurred in both MCF10AT1-derived tumor tissue and endogenously in mammary gland tissue of MR mice. Breast cancer cell lines MCF10A and MDA-MB-231 grown in methionine-restricted cysteine-depleted media for 24 h also up-regulated P21 and P27 gene expression, and MDA-MB-231 cells had decreased proliferation. CONCLUSION: MR hinders cancer progression by increasing cell cycle inhibitors that halt cell cycle progression. The application of MR in a clinical setting may provide a delay in the progression of cancer, which would provide more time for conventional cancer therapies to be effective. PMID- 27255183 TI - Diagnostic accuracy of flexion-extension radiography for the detection of ligamentous cervical spine injury following a normal cervical spine computed tomography. AB - BACKGROUND: Flexion-extension radiography (FER) has been utilised for the detection of ligamentous injury in patients who have been cleared of bony injury. Some studies call into question the diagnostic accuracy of FER, the high proportion of inadequate FER images and the adverse effects of prolonged cervical collar immobilisation although awaiting FER. METHODS: We conducted a two-part retrospective study of trauma patients presenting to a trauma centre between January 2007 and December 2014. A cross-sectional analytic study was used to determine diagnostic accuracy and a case-control design was used to compare characteristics and complications of those having FER with similar patients not having FER. Inclusion criteria were age >=16, blunt trauma mechanism, a normal computed tomography (CT) of the cervical spine and FER to assess for ligamentous injury. The reference standard was magnetic resonance imaging evidence of ligamentous disruption or a therapeutic intervention to treat ligamentous instability. RESULTS: There were 176 participants meeting inclusion criteria. Studies were considered inadequate in 168 participants (95.5%). There were zero true positives, four false positives, 168 true negatives and four false negatives: sensitivity 0% (0.0-60.2%), specificity 97.7 (94.2-99.4%), positive predictive value 0% (0.0-60.2%) and negative predictive value 97.7 (94.2-99.4%). Participants having FER remained in cervical collars and in hospital longer than control patients. Complications of cervical collar use were uncommon. CONCLUSION: FER does not contribute additional diagnostic accuracy for the detection of ligamentous injury to the cervical spine following a normal CT of the cervical spine. We recommend FER be removed from cervical spine clearance protocols. PMID- 27255184 TI - Reducing methane production by supplementation of Terminalia chebula RETZ. containing tannins and saponins. AB - This study investigates the effects of Terminalia chebula Retz. meal supplementation on rumen fermentation and methane (CH4 ) production by using an in vitro gas technique. The experimental design was a completely randomized design (CRD) and the dietary treatments were T. chebula supplementation at 0, 4, 8, 12, 16 and 20 mg with 0.5 g of roughage and concentrate ratio at 60:40. The results revealed that cumulative gas production (96 h of incubation) were higher (P < 0.01) with T. chebula supplementation at 12, 16 and 20 mg than other treatments. However, in vitro dry matter degradability (IVDMD) and in vitro organic matter digestibility (IVOMD) were not significantly different among treatments (P > 0.05). The NH3 -N concentrations tended to quadratically increase with increasing levels of T. chebula in the diet. In addition, total volatile fatty acids (VFA) and propionate concentrations were increased (P < 0.01), while acetate concentration, acetate-to-propionate ratio, CH4 production and protozoal populations were decreased (P < 0.01) when supplemented with T. chebula at 8, 12 and 16 mg, respectively. Based on this study, it could be concluded that supplementation of T. chebula at 12 mg could improve rumen fermentation by reducing CH4 production and protozoa populations, thus improving in vitro gas production and VFA profiles. PMID- 27255185 TI - Middle East Respiratory Syndrome Coronavirus (MERS-CoV) origin and animal reservoir. AB - Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus discovered in 2012 and is responsible for acute respiratory syndrome in humans. Though not confirmed yet, multiple surveillance and phylogenetic studies suggest a bat origin. The disease is heavily endemic in dromedary camel populations of East Africa and the Middle East. It is unclear as to when the virus was introduced to dromedary camels, but data from studies that investigated stored dromedary camel sera and geographical distribution of involved dromedary camel populations suggested that the virus was present in dromedary camels several decades ago. Though bats and alpacas can serve as potential reservoirs for MERS CoV, dromedary camels seem to be the only animal host responsible for the spill over human infections. PMID- 27255186 TI - Alpha fetoprotein antagonizes apoptosis induced by paclitaxel in hepatoma cells in vitro. AB - Hepatocellular carcinoma (HCC) cell resistance to the effects of paclitaxel has not been adequately addressed. In this study, we found that paclitaxel significantly inhibited the viability of HLE, Bel 7402 and L-02 cells in a dose- and time-dependent manner. HLE cells and L-02 cells resisted the cytotoxicity of paclitaxel when transfected with pcDNA3.1-afp vectors. However, Bel 7402 cell sensitivity to paclitaxel was increased when transfected with alpha fetoprotein (AFP)-siRNA. Bel 7402 cell resistance to paclitaxel was associated with the expression of the "stemness" markers CD44 and CD133. Paclitaxel significantly inhibited growth and promoted apoptosis in HLE cells and L-02 cells by inducing fragmentation of caspase-3 and inhibiting the expression of Ras and Survivin, but pcDNA3.1-afp vectors prevented these effects. However, paclitaxel could not significantly promote the cleavage of caspase-3 or suppress the expression of Ras and Survivin in Bel 7402 cells. Silenced expression of AFP may be synergistic with paclitaxel to restrain proliferation and induce apoptosis, enhance cleavage of caspase-3, and suppress the expression of Ras and Survivin. Taken together, AFP may be an important molecule acting against paclitaxel-inhibited proliferation and induced apoptosis in HCC cells via repressing the activity of caspase-3 and stimulating the expression of Ras and Survivin. Targeted inhibition of AFP expression after treatment with paclitaxel is an available strategy for the therapy of patients with HCC. PMID- 27255187 TI - Tissue deposition and toxicological effects of commercially significant rare earth oxide nanomaterials: Material and physical properties. AB - Rare earth oxide (REO) materials are found naturally in earth's crust and at the nanoscale these REO nanoparticles exhibit unique thermal, electrical, and physicochemical properties. REO nanoparticles are widely used in different industrial sectors for ceramics, glass polishing, metallurgy, lasers, and magnets. Recently, some of these REO nanoparticles have been identified for their potential application in medicine, including therapy, imaging, and diagnostics. Concurrent research into the REO nanomaterials' toxicities has also raised concern for their environmental impacts. The correlation of REO nanoparticles mediated toxicity with their physiochemical properties can help to design nanoparticles with minimal effect on the environment and living organisms. In vitro assay revealed toxicity toward Human squamous epithelial cell line (CCL30) and Human umbilical vascular endothelial cells (HUVEC) at a concentration of 100 uM and higher. In vivo results showed, with the exception of CeO2 and Gd2 O3 , most of the naoparticles did not clear or had minimum clearance (10-20%) from the system. Elevated levels of alanine transferase were seen for animals given each different nanoparticle, however the increases were not significant for CeO2 and Dy2 O3 . Nephrotoxicity was only seen in case of Dy2 O3 and Gd2 O3 . Lastly, histological examination revealed presence of swollen hepatocytes which further confirms toxicity of the commercial REO nanomaterials. The in vivo toxicity is mainly due to excessive tissue deposition (70-90%) due to the commercial REO nanoparticles' poor physical properties (shape, stability, and extent of agglomeration). Therefore, optimization of nanoparticles physical properties is very important. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 904-917, 2017. PMID- 27255188 TI - Direct microfabrication of oxide patterns by local electrodeposition of precisely positioned electrolyte: the case of Cu2O. AB - An efficient technique for writing 2D oxide patterns on conductive substrates is proposed and demonstrated in this paper. The technique concerns a novel concept for selective electrodeposition, in which a minimum quantity of liquid electrolyte, through an extrusion nozzle, is delivered and manipulated into the desired shape on the substrate, meanwhile being electrodeposited into the product by an applied voltage across the nozzle and substrate. Patterns of primarily Cu2O with 80~90% molar fraction are successfully fabricated on stainless steel substrates using this method. A key factor that allows the solid product to be primarily oxide Cu2O instead of metal Cu - the product predicted by the equilibrium Pourbaix diagram given the unusually large absolute deposition voltage used in this method, is the non-equilibrium condition involved in the process due to the short deposition time. Other factors including the motion of the extrusion nozzle relative to the substrate and the surface profile of the substrate that influence the electrodeposition performance are also discussed. PMID- 27255189 TI - Generation of open biomedical datasets through ontology-driven transformation and integration processes. AB - BACKGROUND: Biomedical research usually requires combining large volumes of data from multiple heterogeneous sources, which makes difficult the integrated exploitation of such data. The Semantic Web paradigm offers a natural technological space for data integration and exploitation by generating content readable by machines. Linked Open Data is a Semantic Web initiative that promotes the publication and sharing of data in machine readable semantic formats. METHODS: We present an approach for the transformation and integration of heterogeneous biomedical data with the objective of generating open biomedical datasets in Semantic Web formats. The transformation of the data is based on the mappings between the entities of the data schema and the ontological infrastructure that provides the meaning to the content. Our approach permits different types of mappings and includes the possibility of defining complex transformation patterns. Once the mappings are defined, they can be automatically applied to datasets to generate logically consistent content and the mappings can be reused in further transformation processes. RESULTS: The results of our research are (1) a common transformation and integration process for heterogeneous biomedical data; (2) the application of Linked Open Data principles to generate interoperable, open, biomedical datasets; (3) a software tool, called SWIT, that implements the approach. In this paper we also describe how we have applied SWIT in different biomedical scenarios and some lessons learned. CONCLUSIONS: We have presented an approach that is able to generate open biomedical repositories in Semantic Web formats. SWIT is able to apply the Linked Open Data principles in the generation of the datasets, so allowing for linking their content to external repositories and creating linked open datasets. SWIT datasets may contain data from multiple sources and schemas, thus becoming integrated datasets. PMID- 27255190 TI - Determinants of sleep disturbances in Rett syndrome: Novel findings in relation to genotype. AB - Rett syndrome is a rare but severe neurological disorder associated with a mutation in the methyl CpG binding protein 2 (MECP2) gene. Sleep problems and epilepsy are two of many comorbidities associated with this disorder. This study investigated the prevalence and determinants of sleep problems in Rett syndrome using an international sample. Families with a child with a confirmed Rett syndrome diagnosis and a MECP2 mutation registered in the International Rett Syndrome Phenotype Database (InterRett) were invited to participate. Questionnaires were returned by 364/461 (78.9%) either in web-based or paper format. Families completed the Sleep Disturbance Scale for Children and provided information on the presence, nature, and frequency of their child's sleep problems. Multivariate multinomial regression was used to investigate the relationships between selected sleep problems, age group, and genotype and linear regression for the relationships between sleep disturbance scales and a range of covariates. Night waking was the most prevalent sleep problem affecting over 80% with nearly half (48.3%) currently waking often at night. Initiating and maintaining sleep was most disturbed for younger children and those with a p.Arg294* mutation. Severe seizure activity was associated with poor sleep after adjusting for age group, mutation type, and mobility. We were surprised to find associations between the p.Arg294* mutation and some sleep disturbances given that other aspects of its phenotype are milder. These findings highlight the complexities of aberrant MECP2 function in Rett syndrome and explain some of the variation in manifestation of sleep disturbances. (c) 2016 Wiley Periodicals, Inc. PMID- 27255192 TI - [A reconsideration of Tui and the original model of Jueyin]. AB - Revelation of the intrinsic characteristics of"tui"led to questioning of the"hypothesis that tui refers to Bancroftianfilariasis". The analysis of medical bamboo slips from the Han Dynasty unearthed in Wuwei proved that the disease referred to as"Tuo Xia Yang Shi(subscrotalmoistitch)"in these slips was most probably the one now known as Bancroftianfilariasis. The decipherment of numerous bamboo slips from the Chu State that are considered to date back to the period of Warring States revealed that the predecessor to Jue Yin disease was named"or or or or )D or A or C or F or H"; however, medical texts from Mawangdui and Mount Zhangjia refer to this disease as"tui(,>,)"and"tui()"respectively, whereas HuangdiNeijing (The Yellow Emperor's Inner Classic) renames this disease as"tui(,,)", revealing that everything was rendered phonetically. PMID- 27255194 TI - [Textual research on the fire needle and the fire needle therapy]. AB - There are different names of the fire needle therapy in the Huang di nei jing (Inner Canon of Huangdi) such as Zu-zhen (), Cui-zhen (,), Fan-zhen (), Huo-cui (), Cui (,,), Cuici ,), Fan zhen jie ci (). It is claimed that the lance needle, the round sharp needle and the long needle recorded in this Classic are puncturing tools for the fire needle therapy. In the Eastern Han Dynasty, Zhang Zhongjing expanded the indications for the fire needle therapy and Huo-zhen () firstly appeared in the Jin kui yu han jing(Classic of the Jade Box and Golden Chamber). The application of the fire needle therapy had been further expanded to a lot of internal and external disorders form the Wei-Jin-Southern and Northern Dynasties to the Ming and Qing Dynasties. There are more detailed records on the manipulation and the tools of the fire needle therapy during this period. In the 1970s, Huo zhen liao fa () was proposed and still in use today. However the Bai zhen (plain needle) in ancient literature is equal to the filiform needle and should not be regarded as the former name of the fire needle. PMID- 27255195 TI - [Classes of crude drugs and its distribution of producing area in the attached illustrations in Ben cao tu jing (Illustrated Classic of Materia Medica)]. AB - Ben cao tu jing (Illustrated Classic of Materia Medica) is the earliest extant atlas book of materia medica in China, with 933 attached drawings. Among them, the largest portion, amounting to 670, are herbaceous plants, mostly commonly used, with definite marks of the origin producing areas, distributed across 149 administrative divisions(prefectures and counties) of the Song Dynasty, most of them in Northern area which were distributed denser than those in Southern area. The densest ones were located in Southern Shanxi, Eastern Sichuan and Eastern Anhui. In the attached drawings, the frequency of highest occurrence appeared in this Classic are three prefectures, Chuzhou, Shizhou and Guangzhou. PMID- 27255191 TI - A 3D in vitro model to explore the inter-conversion between epithelial and mesenchymal states during EMT and its reversion. AB - Epithelial-to-mesenchymal transitions (EMT) are strongly implicated in cancer dissemination. Intermediate states, arising from inter-conversion between epithelial (E) and mesenchymal (M) states, are characterized by phenotypic heterogeneity combining E and M features and increased plasticity. Hybrid EMT states are highly relevant in metastatic contexts, but have been largely neglected, partially due to the lack of physiologically-relevant 3D platforms to study them. Here we propose a new in vitro model, combining mammary E cells with a bioengineered 3D matrix, to explore phenotypic and functional properties of cells in transition between E and M states. Optimized alginate-based 3D matrices provided adequate 3D microenvironments, where normal epithelial morphogenesis was recapitulated, with formation of acini-like structures, similar to those found in native mammary tissue. TGFbeta1-driven EMT in 3D could be successfully promoted, generating M-like cells. TGFbeta1 removal resulted in phenotypic switching to an intermediate state (RE cells), a hybrid cell population expressing both E and M markers at gene/protein levels. RE cells exhibited increased proliferative/clonogenic activity, as compared to M cells, being able to form large colonies containing cells with front-back polarity, suggesting a more aggressive phenotype. Our 3D model provides a powerful tool to investigate the role of the microenvironment on metastable EMT stages. PMID- 27255196 TI - [Zheng Meijian's Sha yu yi yu (Random Medical Talks in Leisure Time) and his new ideas on pulse-taking]. AB - Zheng Meijian, a doctor of Xin'an district in the reign of Qianlong Emperor of the Qing Dynasty, left his manuscript Sha yu yi yu (Random Medical Talks in Leisure Time), and was handed down in his family for generations. Sha yu yi yu was published in the Anhui Yixue of Issue 20, 1959, with horizontal layout and punctuation. The book records Zheng Meijian's understanding for the medicine, especially his new ideas on the cunkou pulse, with its underlying corresponding relationship among cun-guan-chi and zang-fu which should be combined with meridian and collateral system, claiming that the pulse taken superficially was corresponding to fu, while that taken deeply, to zang. He classified the strength of the fingers in pulse-taking into 8 levels, and advocated flexible application of pulse-taking. All his opinions had an important reference value for theoretical research and clinical application of pulse-taking. PMID- 27255197 TI - [Textual research on wei sheng (hygiene) and gong gong wei sheng (public health)]. AB - Wei sheng, a verb-object word group existed since the ancient time, referring to"protection of life", and it was evolved as a single word which can be translated as"hygiene"in modern times with multiple implications like"cleanliness","sterilization", and"prevention of disease", etc. Gong gong wei sheng was isolated from"hygiene", which has become a new term. In the Republic of China, scholars had made preliminary studies on the translation of"hygiene"during which gong gong wei sheng, and"guo min wei sheng"(national hygiene) and"gong zhong wei sheng"(people's hygiene) appeared also. Though the term"public health"was defined by the WHO and gong gong wei sheng was defined by Chinese scholars with gradual improvement, yet, the implications of both terms are still imperfect. PMID- 27255198 TI - [Early history of medicine and health career in Harbin]. AB - Harbin, located in the northeast of China, was still an agricultural region dominated by traditional natural economy in the late 19th century. Harbin became the"Eurasia land bridge"and the transportation junction of the northeast railway network, along with the building of Mid-east railway in 1898, which sped up the development of the city. With the influx of foreign workers and capital, in the 1930s, Harbin has become a city with 19 countries' consulates and nearly 100, 000 people from more than 20 foreign countries. In this international multicultural city, the rapid introduction and spread of western medicine showed the great effect for the development of medicine and health career, ranking the top in China. PMID- 27255199 TI - [Textual research on decipher of"prescriptions for treating children's head sore"from Zhi re bing yao lun (Essentials on Treatment of Febrile Diseases) in the Western Xia regime]. AB - There were 3 prescriptions for treating children's head sore, inv6476-28, 29, 30 preserved in Russia, included in the Zhi re bing yao lun (Essentials on Treatment of Febrile Diseases), a medical literature of the Western Xia regime. Based on the correlated relationship between the Tangut language and the Chinese characters, the 3 prescriptions were translated into Chinese, and then compared with Chinese medical documents. It could be seen that medical system in the Western Xia regime had an inseparable relationship with that of the Han nationality, while keeping the features of the northwestern nomadic nationalities at the same time. PMID- 27255200 TI - [Research on the"Association of Han medicine of State of Manchuria"]. AB - The"Association of Han medicine of State of Manchuria"was a puppet TCM academic society founded by the Puppet Manchukuo government, with well-organization system and widespread scope. During its period, though some efforts were made to promoting the TCM academic progress, improving the quality of TCM doctors, developing TCM clinic, education, academic research and administration, its essence was still a tool for the puppet government to controlling, transforming and utilizing TCM. PMID- 27255201 TI - Erratum to: 'Ultra-precise detection of mutations by droplet-based amplification of circularized DNA'. PMID- 27255202 TI - Barbara Williams. PMID- 27255203 TI - Clinical characteristics of atrial fibrillation-related cardioembolic stroke in patients aged 80 years or older. AB - AIM: Atrial fibrillation (AF)-related cardioembolic stroke is a serious problem in the aging society. The present study examined the clinical characteristics and outcomes of AF-related cardioembolic stroke in patients aged >=80 years. METHODS: Between September 2011 and April 2014, consecutive patients with ischemic stroke and AF were retrospectively extracted from the multicenter database. Clinical characteristics were compared between patients aged >=80 years and <80 years. Multivariate cox proportional hazard models were used to estimate hazard ratios and 95% confidential intervals on 90-day mortality for age of >=80 years. RESULTS: A total of 253 patients aged >=80 years (87 men, 86.4 +/- 5.0 years) and 196 patients aged <80 years (134 men, 70.4 +/- 7.1 years) were included. Patients aged >=80 years were more frequently female, and more likely to have higher premorbid modified Rankin Scale score (mRS), lower body mass index, previous history of stroke, prior antiplatelet therapy, congestive heart failure, and persistent AF. Patients aged >=80 years had higher initial National Institutes of Health Stroke Scale score and were more likely to have occlusion of the cervicocephalic arteries, but less likely to receive thrombolysis. Patients aged >=80 years had a higher mRS and mortality after 3 months. Age of >=80 years was a significant predictor of 90-day mortality after adjustment for sex (hazard ratio 2.20, 95% confidential interval 1.25-4.09), but was no longer significant after further adjustment for other clinical characteristics and stroke severity. CONCLUSIONS: In AF-related cardioembolic stroke, patients aged >=80 years had different clinical characteristics and poorer outcome compared with patients aged <80 years. Geriatr Gerontol Int 2017; 17: 708-713. PMID- 27255204 TI - Characterisation of Exposure to Ultrafine Particles from Surgical Smoke by Use of a Fast Mobility Particle Sizer. AB - INTRODUCTION: Electrosurgery is a method based on a high frequency current used to cut tissue and coagulate small blood vessels during surgery. Surgical smoke is generated due to the heat created by electrosurgery. The carcinogenic potential of this smoke was assumed already in the 1980's and there has been a growing interest in the potential adverse health effects of exposure to the particles in surgical smoke. Surgical smoke is known to contain ultrafine particles (UFPs) but the knowledge about the exposure to UFPs produced by electrosurgery is however sparse. The aims of the study were therefore to characterise the exposure to UFPs in surgical smoke during different types of surgical procedures and on different job groups in the operating room, and to characterise the particle size distribution. METHODS: Personal exposure measurements were performed on main surgeon, assistant surgeon, surgical nurse, and anaesthetic nurse during five different surgical procedures [nephrectomy, breast reduction surgery, abdominoplasty, hip replacement surgery, and transurethral resection of the prostate (TURP)]. The measurements were performed with a Fast Mobility Particle Sizer (FMPS) to assess the exposure to UPFs and to characterize the particle size distribution. Possible predictors of exposure were investigated using Linear Mixed Effect Models. RESULTS: The exposure to UFPs was highest during abdominoplasty arithmetic mean (AM) 3900 particles cm(-3) and lowest during hip replacement surgeries AM 400 particles cm(-3). The different job groups had similar exposure during the same types of surgical procedures. The use of electrosurgery resulted in short term high peak exposure (highest maximum peak value 272 000 particles cm(-3)) to mainly UFPs. The size distribution of particles varied between the different types of surgical procedures, where nephrectomy, hip replacement surgery, and TURP produced UFPs with a dominating mode of 9nm while breast reduction surgery and abdominoplasty produced UFPs with a dominating mode of 70 and 81nm, respectively. Type of surgery was the strongest predictor of exposure. When only including breast reduction surgery in the analysis, the use of one or two ES pencils during surgery was a significant predictor of exposure. When only including hip replacement surgery, the operating room was a significant predictor of exposure. CONCLUSION: The use of electrosurgery resulted in short-term high peak exposures to mainly UFPs in surgical smoke. Type of surgery was the strongest predictor of exposure and the different types of surgical procedures produced different sized particles. The job groups had similar exposure. Compared to other occupational exposures to UFPs involving hot processes, the personal exposure levels for UFPs were low during the use of electrosurgery. PMID- 27255205 TI - Ethics dilemmas of early detection of obesity. AB - AIM: To discuss the ethics dilemmas of the early detection of overweight and obesity. METHODS: Analysis of the ethical aspects of early detection. RESULTS: The early detection of overweight and obesity entails a number of ethical dilemmas because it may both be helpful and harmful. It may help people to lead a healthier life and non-detection could be considered neglectful. It may, however, cause anxiety, interfere with people's integrity, focus only on individual causes and responsibilities, cause stigmatization and have adverse effects by inducing weight gain. CONCLUSIONS DOCUMENTATION OF MORE POSITIVE THAN NEGATIVE EFFECTS IS REQUIRED BEFORE EARLY DETECTION IS INTRODUCED. PMID- 27255206 TI - Richard Nesbit Evans. PMID- 27255207 TI - Mobile health solutions for the aging population: A systematic narrative analysis. AB - Introduction The ubiquitous nature of mobile technology coupled with the acceptance of mobile health (mHealth) among the elderly offers an opportunity to augment the existing medical workforce in long-term care. The objective of this review and narrative analysis is to identify and analyse facilitators and barriers to adoption of mHealth for the elderly. Methods Studies over the last year were identified in multiple database indices, and three reviewers examined abstracts ( k = 0.82) and analysed articles for themes which were tallied in affinity diagrams to identify frequency of occurrence in the literature (n = 36). Results The three facilitators mentioned most often were independence (18%), understanding (13%), and visibility (13%). The three barriers mentioned most often were complexity (21%), limited by users (12%) and ineffective (12%). Discussion and conclusions The reviewers concluded that the work done so far illustrates that mHealth enables a perception of independence. Future research should focus on the barriers of complexity of technology and improving existing medical literacy in order to facilitate further adoption. PMID- 27255208 TI - New Edges of RNA Adenosine Methylation Modifications. PMID- 27255209 TI - Photoelectrochemical water splitting enhanced by self-assembled metal nanopillars embedded in an oxide semiconductor photoelectrode. AB - Production of chemical fuels by direct solar energy conversion in a photoelectrochemical cell is of great practical interest for developing a sustainable energy system. Various nanoscale designs such as nanowires, nanotubes, heterostructures and nanocomposites have been explored to increase the energy conversion efficiency of photoelectrochemical water splitting. Here we demonstrate a self-organized nanocomposite material concept for enhancing the efficiency of photocarrier separation and electrochemical energy conversion. Mechanically robust photoelectrodes are formed by embedding self-assembled metal nanopillars in a semiconductor thin film, forming tubular Schottky junctions around each pillar. The photocarrier transport efficiency is strongly enhanced in the Schottky space charge regions while the pillars provide an efficient charge extraction path. Ir-doped SrTiO3 with embedded iridium metal nanopillars shows good operational stability in a water oxidation reaction and achieves over 80% utilization of photogenerated carriers under visible light in the 400- to 600-nm wavelength range. PMID- 27255211 TI - Value of transvaginal sonography after cervical cerclage. PMID- 27255210 TI - Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model. AB - INTRODUCTION: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS: This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS: Compared with the HF group, attenuated atrial fibrosis (35.4 +/- 17.4% vs. 16.9 +/- 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 +/- 3.4% vs. 68.0 +/- 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 +/- 6.8 vs. 94.3 +/- 1.2, P = 0.002), APD90 (89.3 +/- 1.5 vs. 112.7 +/- 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 +/- 0.04 vs. 0.42 +/- 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS: Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling. PMID- 27255212 TI - A systematic review of randomised controlled trials in rheumatoid arthritis: the reporting and handling of missing data in composite outcomes. AB - BACKGROUND: Most reported outcome measures in rheumatoid arthritis (RA) trials are composite, whose components comprise single measures that are combined into one outcome. The aims of this review were to assess the range of missing data rates in primary composite outcomes and to document the current practice for handling and reporting missing data in published RA trials compared to the Consolidated Standards of Reporting Trials (CONSORT) recommendations. METHODS: A systematic search for randomised controlled trials was conducted for RA trials published between 2008 and 2013 in four rheumatology and four high impact general medical journals. RESULTS: A total of 51 trials with a composite primary outcome were identified, of which 38 (75 %) used the binary American College of Rheumatology responder index and 13 (25 %) used the Disease Activity Score for 28 joints (DAS28). Forty-four trials (86 %) reported on an intention-to-treat analysis population, while 7 trials (14 %) analysed according to a modified intention-to-treat population. Missing data rates for the primary composite outcome ranged from 2-53 % and were above 30 % in 9 trials, 20-30 % in 11 trials, 10-20 % in 18 trials and below 10 % in 13 trials. Thirty-eight trials (75 %) used non-responder imputation and 10 (20 %) used last observation carried forward to impute missing composite outcome data at the primary time point. The rate of dropout was on average 61 % times higher in the placebo group compared to the treatment group in the 34 placebo controlled trials (relative rate 1.61, 95 % CI: 1.29, 2.02). Thirty-seven trials (73 %) did not report the use of sensitivity analyses to assess the handling of missing data in the primary analysis as recommended by CONSORT guidelines. CONCLUSIONS: This review highlights an improvement in rheumatology trial practice since the revision of CONSORT guidelines, in terms of power calculation and participant's flow diagram. However, there is a need to improve the handling and reporting of missing composite outcome data and their components in RA trials. In particular, sensitivity analyses need to be more widely used in RA trials because imputation is widespread and generally uses single imputation methods, and in this area the missing data rates are commonly differentially higher in the placebo group. PMID- 27255213 TI - Local adaptations to a global health initiative: penalties for home births in Zambia. AB - Global health initiatives (GHIs) are implemented across a variety of geographies and cultures. Those targeting maternal health often prioritise increasing facility delivery rates. Pressure on local implementers to meet GHI goals may lead to unintended programme features that could negatively impact women. This study investigates penalties for home births imposed by traditional leaders on women during the implementation of Saving Mothers, Giving Life (SMGL) in Zambia. Forty focus group discussions (FGDs) were conducted across four rural districts to assess community experiences of SMGL at the conclusion of its first year. Participants included women who recently delivered at home (3 FGDs/district), women who recently delivered in a health facility (3 FGDs/district), community health workers (2 FGDs/district) and local leaders (2 FGDs/district). Findings indicate that community leaders in some districts-independently of formal programme directive-used fines to penalise women who delivered at home rather than in a facility. Participants in nearly all focus groups reported hearing about the imposition of penalties following programme implementation. Some women reported experiencing penalties firsthand, including cash and livestock fines, or fees for child health cards that are typically free. Many women who delivered at home reported their intention to deliver in a facility in the future to avoid penalties. While communities largely supported the use of penalties to promote facility delivery, the penalties effectively introduced a new tax on poor rural women and may have deterred their utilization of postnatal and child health care services. The imposition of penalties is thus a punitive adaptation that can impose new financial burdens on vulnerable women and contribute to widening health, economic and gender inequities in communities. Health initiatives that aim to increase demand for health services should monitor local efforts to achieve programme targets in order to better understand their impact on communities and on overall programme goals. PMID- 27255214 TI - Hierarchical Targeting Strategy for Enhanced Tumor Tissue Accumulation/Retention and Cellular Internalization. AB - Targeted delivery of therapeutic agents is an important way to improve the therapeutic index and reduce side effects. To design nanoparticles for targeted delivery, both enhanced tumor tissue accumulation/retention and enhanced cellular internalization should be considered simultaneously. So far, there have been very few nanoparticles with immutable structures that can achieve this goal efficiently. Hierarchical targeting, a novel targeting strategy based on stimuli responsiveness, shows good potential to enhance both tumor tissue accumulation/retention and cellular internalization. Here, the recent design and development of hierarchical targeting nanoplatforms, based on changeable particle sizes, switchable surface charges and activatable surface ligands, will be introduced. In general, the targeting moieties in these nanoplatforms are not activated during blood circulation for efficient tumor tissue accumulation, but re-activated by certain internal or external stimuli in the tumor microenvironment for enhanced cellular internalization. PMID- 27255215 TI - The nine-year changes of the incidence and characteristics of metabolic syndrome in China: longitudinal comparisons of the two cross-sectional surveys in a newly formed urban community. AB - BACKGROUND: To assess the 9-year changes of the incidence and characteristics of metabolic syndrome (MetS) in Chinese community under the background of dramatically changed environment. METHODS: Two cross-sectional surveys of the general population were carried out in 2005 and 2014 in Dengmin and Hongnan villages of Fengcheng community, a newly formed urban community from rural area 10 years ago. All permanent adult residents aged 18-80 without active malignant tumors and pregnancy were invited to attend the study. They participated in clinical examinations for anthropometric and blood pressure measurements. Fasting blood samples were drawn for analysis of lipids and glucose. Presence of MetS was defined based on the IDF/AHA harmonized criteria. MetS z-score was calculated to evaluate the degree of total metabolic disorder. RESULTS: A total of 1042 subjects in 2005 and 1053 subjects in 2014 were included in the final analysis. The participants were stratified by gender. The incidence of MetS was higher in 2014 than 2005 in both genders (female, 48.28 vs 31.61 %; male, 41.12 vs 26.30 %; p value, both <0.001). Of the five MetS components, the FBG and TG levels were higher in 2014 than 2005 in both gender, however, the SBP and DBP values were even lower in 2014 than 2005. The differences of FBG, blood pressure and lipid levels between 2005 and 2014 still exist after ruling out recognized diabetic, hypertensive and dyslipidemic subjects, individually. In MetS subjects, MetS z score showed the whole metabolic profile get worse in 2014 than 2005 in both sex (female, 1.97 +/- 2.53 vs 1.74 +/- 2.29; male, 2.51 +/- 2.79 vs 1.01 +/- 2.38. both P < 0.001). Using 3 abnormal components as a combination, we found the frequency of different kinds of combination also changed in MetS subjects. In female, the combination of WC + BP + HDL disorder decreased from 29.7 % (2005) to 11.0 % (2014) and WC + FBG + BP disorder became the most popular phenotype (18.8 %) in 2014. CONCLUSIONS: The dramatically changed environments have extensive influence on metabolic parameters of local residents. More targeted measures need to be taken to meet the serious challenges of metabolic diseases. Trial registration ChiCTR-ECS-14005052, http://www.chictr.org, Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China). PMID- 27255216 TI - Flow cytometry may allow microscope-independent detection of holocentric chromosomes in plants. AB - Two chromosomal structures, known as monocentric and holocentric chromosomes, have evolved in eukaryotes. Acentric fragments of monocentric chromosomes are unequally distributed to daughter cells and/or lost, while holocentric fragments are inherited normally. In monocentric species, unequal distribution should generate chimeras of cells with different nuclear DNA content. We investigated whether such differences in monocentric species are detectable by flow cytometry (FCM) as (i) a decreased nuclear DNA content and (ii) an increased coefficient of variance (CV) of the G1 peak after gamma radiation-induced fragmentation. We compared 13 monocentric and 9 holocentric plant species. Unexpectedly, monocentrics and holocentrics did not differ with respect to parameters (i) and (ii) in their response to gamma irradiation. However, we found that the proportion of G2 nuclei was highly elevated in monocentrics after irradiation, while holocentrics were negligibly affected. Therefore, we hypothesize that DNA damaging agents induce cell cycle arrest leading to endopolyploidy only in monocentric and not (or to much lesser extent) in holocentric plants. While current microscope-dependent methods for holocentrism detection are unreliable for small and numerous chromosomes, which are common in holocentrics, FCM can use somatic nuclei. Thus, FCM may be a rapid and reliable method of high-throughput screening for holocentric candidates across plant phylogeny. PMID- 27255218 TI - Transcriptome profiling of the antiviral immune response in Atlantic cod macrophages. AB - A study was conducted to determine the transcriptome response of Atlantic cod (Gadus morhua) macrophages to the viral mimic, polyriboinosinic polyribocytidylic acid (pIC), using a 20K Atlantic cod microarray platform and qPCR. We identified 285 significantly up-regulated and 161 significantly down-regulated probes in cod macrophages 24 h after pIC stimulation. A subset of 26 microarray-identified transcripts was subjected to qPCR validation using samples treated with pIC or phosphate-buffered saline (control) over time (3, 6, 12, 24, 48 h), and 77% of them showed a significant response to pIC. The microarray and qPCR analyses in this study showed that pIC induced the expression of cod macrophage transcripts involved in RLR- and TLR-dependent pathogen recognition (e.g. tlr3, tlr7, mda5 and lgp2), as well as signal transducers (e.g. stat1 and nfkbia) and transcription activators (e.g. irf7 and irf10) in the MyD88-independent and dependent signalling pathways. Several immune effectors (e.g. isg15s, viperin, herc4, mip2 and ccl13) were significantly up-regulated in pIC-stimulated cod macrophages. The expression of some transcripts (e.g. irf7, irf10, viperin) was significantly up-regulated by pIC as early as 12 h. All pIC-induced transcripts had peak expression at either 24 h (e.g. tlr7, irf7, mip2) or 48 h (e.g. tlr3, lgp2, stat1). This study suggests possible roles of both vertebrate-conserved (e.g. tlr3 as an up-regulated gene) and fish-specific (tlr22g as a down-regulated gene) receptors in dsRNA recognition, and the importance of conserved and potentially fish-specific interferon stimulated genes in cod macrophages. PMID- 27255217 TI - An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation. AB - CaV1.3 channels are a major class of L-type Ca(2+) channels which contribute to the rhythmicity of the heart and brain. In the brain, these channels are vital for excitation-transcription coupling, synaptic plasticity, and neuronal firing. Moreover, disruption of CaV1.3 function has been associated with several neurological disorders. Here, we focus on the de novo missense mutation A760G which has been linked to autism spectrum disorder (ASD). To explore the role of this mutation in ASD pathogenesis, we examined the effects of A760G on CaV1.3 channel gating and regulation. Introduction of the mutation severely diminished the Ca(2+)-dependent inactivation (CDI) of CaV1.3 channels, an important feedback system required for Ca(2+) homeostasis. This reduction in CDI was observed in two major channel splice variants, though to different extents. Using an allosteric model of channel gating, we found that the underlying mechanism of CDI reduction is likely due to enhanced channel opening within the Ca(2+)-inactivated mode. Remarkably, the A760G mutation also caused an opposite increase in voltage dependent inactivation (VDI), resulting in a multifaceted mechanism underlying ASD. When combined, these regulatory deficits appear to increase the intracellular Ca(2+) concentration, thus potentially disrupting neuronal development and synapse formation, ultimately leading to ASD. PMID- 27255219 TI - Characterization of a Kunitz-type protease inhibitor (MjKuPI) reveals the involvement of MjKuPI positive hemocytes in the immune responses of kuruma shrimp Marsupenaeus japonicus. AB - Serine proteases and their inhibitors play vital roles in biological processes. Serine protease inhibitors, including Kunitz-type protease inhibitors play important roles not only in physiological process (i.e. blood clotting and fibrinolysis) but also in immune responses. In this study, we characterized a Kunitz-type protease inhibitor, designated MjKuPI, from kuruma shrimp Marsupenaeus japonicus. An expression profile showed that MjKuPI was mainly expressed in hemocytes. Immunostaining revealed that some hemocytes expressed MjKuPI (MjKuPI(+) hemocytes) and others did not (MjKuPI(-) hemocytes). Injection of shrimp with Vibrio penaeicida and white spot syndrome virus (WSSV) upregulated the mRNA level of MjKuPI, and a flow cytometry analysis revealed that the proportion of MjKuPI(+) hemocytes increased significantly 24 h after injection. Together, these results suggest that MjKuPI and MjKuPI(+) hemocytes have a role in the innate immune system of kuruma shrimp. PMID- 27255220 TI - Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey. AB - This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liege, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4 +/- 10.4 % vs. 90.3 +/- 6.6 %, p = 0.0013; antibiotics documented 87.9 +/- 9.0 % vs. 95.6 +/- 5.1 %, p < 0.0001; and duration or review date documented 31.9 +/- 15.4 % vs. 67.7 +/- 15.2 %, p < 0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators. PMID- 27255221 TI - Neisseria gonorrhoeae antimicrobial susceptibility in Barcelona: penA, ponA, mtrR, and porB mutations and NG-MAST sequence types associated with decreased susceptibility to cephalosporins. AB - The aims of this study were to determine the antimicrobial susceptibility of Neisseria gonorrhoeae (NG) in our area, to analyze the molecular mechanisms involved in cephalosporins resistance, and to undertake molecular typing of our NG strains. Antimicrobial susceptibility was determined using the Etest. The genes penA, mtrR, penB, and ponA were studied. Molecular typing was performed by N. gonorrhoeae multiantigen sequence typing. Of 329 strains analyzed in 2013, none showed high-level cephalosporin resistance, but 8.2 % had resistance to cefixime [minimum inhibitory concentration (MIC) > 0.125 MUg/mL] and 0.6 % to ceftriaxone (MIC > 0.125 MUg/mL). Azithromycin resistance was documented in 4.3 % and ciprofloxacin resistance in 49.2 %. Among 48 strains with an MIC >= 0.125 MUg/mL to cefixime, 58.3 % showed the penA mosaic pattern XXXIV, 98 % a Leu -> Pro substitution at position 421 of the ponA gene, 100 % amino acid changes at positions 101 and 102 of the PorB1b porin, and 87.5 % of strains an adenine deletion in the promoter region of the MtrC-D-E efflux pump. A significant difference between strains with and without decreased cephalosporin susceptibility (MIC >= 0.125 MUg/mL) was observed for these four genes. Of the 48 strains with an MIC >= 0.125 MUg/mL to cefixime, 43.8 % belonged to the genogroup G1407 and 27.1 % belonged to the genogroup G2400. A significant association of G1407 with decreased susceptibility (MIC >= 0.125 MUg/mL) and G2992 with susceptibility was found, and also between G1407 and mosaic pattern XXXIV and between G2400 and A501T substitution in penA. The NG resistance rate in our area is higher than the median of Europe. We have detected the emergence of G2400, which may be a source of antimicrobial resistance. PMID- 27255222 TI - Efficient Microscale Basic Reverse Phase Peptide Fractionation for Global and Targeted Proteomics. AB - Analysis of small biological samples would benefit from an efficient microscale fractionation strategy that minimizes sample handling, transfer steps, and accompanying losses. Here we describe a microscale basic reverse phase liquid chromatographic (bRPLC) fractionation method that offers high reproducibility and efficiency for peptide mixtures from small (5-20 MUg) samples. We applied our platform to detect differentially expressed proteins from lung tumor cell lines that are sensitive (11-18) and resistant (11-18R) to the tyrosine kinase inhibitor erlotinib. Label-free analyses of 5-20 MUg samples yielded identifications of approximately 3,200 to 4,000 proteins with coefficients of variation of 1.9-8.9% in replicate analyses. iTRAQ analyses produced similar protein inventories. Label-free and iTRAQ analyses displayed high concordance in identifications of proteins differentially expressed in 11-18 and 11-18R cells. Micro-bRPLC fractionation of cell proteomes increased sensitivity by an average of 4.5-fold in targeted quantitation using parallel reaction monitoring for three representative receptor tyrosine kinases (EGFR, PDGFRA, and BMX), which are present at low abundance in 11-18 and 11-18R cells. These data illustrate the broad utility of micro-bRPLC fractionation for global and targeted proteomic analyses. Data are available through Proteome eXchange Accession PXD003604. PMID- 27255223 TI - The distance of visual targets affects the spatial magnitude and multifractal scaling of standing body sway in younger and older adults. AB - The spatial magnitude of standing body sway is greater during viewing of more distant targets and reduced when viewing nearby targets. Classical interpretations of this effect are based on the projective geometry of changes in visual stimulation that are brought about by body sway. Such explanations do not motivate predictions about the temporal dynamics of body sway. We asked whether the distance of visible targets would affect both the spatial magnitude and the multifractality of standing body sway. It has been suggested that the multifractality of movement may change with age. Separately, previous research has not addressed the effects of target distance on postural sway in older adults. For these reasons, we crossed our variation in target distance with variation in age. In an open-air setting, we measured standing body sway in younger and older adults while looking at visual targets that were placed at three distances. The distance of visual targets affected the spatial magnitude of body sway in younger adults, replicating past studies. Target distance also affected the spatial magnitude of sway in older adults, confirming that this relation persists despite other age-related changes. Target distance also affected the multifractality of body sway, but this effect was modulated by age. Finally, the width of the multifractal spectrum was greater for older adults than for younger adults, revealing that healthy aging can affect the multifractality of movement. These findings reveal similarities and differences between the spatial magnitude and the multifractality of human movement. PMID- 27255224 TI - [Thrombotic microangiopathy : Relevant new aspects for intensive care physicians]. AB - Thrombotic microangiopathy (TMA) is a clinical syndrome that is characterized by hemolysis, thrombocytopenia, and acute kidney injury, known as atypical hemolytic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and shigatoxin associated HUS (STEC-HUS) among others. Several diseases, like malignoma, infections, malignant hypertension, or autoimmune disease can result in secondary TMAs. aHUS is caused by a hyperactivated complement system. Identification of the underlying causes of the TMA is the most important issue and directly associated with treatment success. In case of secondary TMAs, treatment of the actual disease is the most important step, while in case of complement-mediated HUS treatment of choice is plasma exchange or anticomplement agents. For the treatment of TTP, rapid initiation of plasma exchange or plasma infusion is the treatment of choice. Patients with STEC-HUS should solely receive supportive treatment. PMID- 27255225 TI - [Thrombocytopenia in the intensive care unit : Diagnosis, differential diagnosis, and treatment]. AB - Thrombocytopenia is a frequent phenomenon in intensive care medicine. A variety of conditions can be responsible for low platelet counts. As platelets are part of the primary hemostatic system, bleeding is the most important complication of thrombocytopenia. Proper workup of the differential diagnosis to identify the cause of thrombocytopenia is essential because the various underlying disorders require different diagnostic and therapeutic management strategies. A low platelet count is a strong predictor of outcome in critically ill patients.This article summarizes the differential diagnosis and diagnostic workup of thrombocytopenia in the critically ill, describes the most important conditions, and gives an overview on therapeutic options and strategies. PMID- 27255226 TI - [Hemodynamic monitoring of critically ill patients : Bedside integration of data]. AB - BACKGROUND: Hemodynamic monitoring of critically ill patients is a key issue in intensive care medicine. Indication and application of invasive hemodynamic monitoring is a highly complex matter and requires thorough professional education and training. MATERIALS AND METHODS: A literature review was performed. RESULTS: A pragmatic approach can be divided into several steps such as medical history, physical examination, imaging, and laboratory results, which support the primary working diagnosis and allow further clarification of the underlying pathophysiology. Invasive arterial blood pressure and cardiac output measurement as well as components of the functional hemodynamic monitoring help to assess fluid responsiveness and to guide volume loading, diuretic therapy as well as administration of vasoactive or positive inotrope substances. CONCLUSIONS: All information gathered through medical history, physical examination, imaging, and hemodynamic monitoring help to form an overall picture and should be reevaluated regularly and in individual cases very closely depending on the hemodynamic instability of the patient. Target values are strictly indicative and are not binding taking into account that each patient has its unique pathophysiological profile. PMID- 27255227 TI - [Pathoanatomical and clinical aspects of the placenta in preterm birth]. AB - BACKGROUND: Prematurely born children show a clearly elevated risk for perinatal morbidity, long-term pediatric morbidities and development of chronic diseases in adulthood compared to babies born at term. The pathoanatomical investigation of placentas from preterm births is useful for assessing the etiology, the risk of recurrence and the prognosis for the child. AIMS: The focus is on presenting the clinical and pathoanatomical characteristics of acute chorioamnionitis as a frequent cause of preterm induction of labor and pregnancy-induced hypertension, in particular preeclampsia as a frequent reason for elective cesarean section. Other lesions, sometimes of unclear etiology associated with preterm birth and substantially elevated risk of recurrence are reviewed. The clinical correlations and therapeutic options of the various diseases are discussed taking the risk of recurrence into consideration. MATERIAL AND METHODS: Examination of placentas, association with the clinical course and a literature search. RESULTS AND DISCUSSION: Acute chorioamnionitis and omphalovasculitis can be histologically subdivided into different stages which correlate with the clinical severity and the prognosis for the newborn child. Chronic deciduitis, chronic chorioamnionitis, villitis of unknown etiology, massive perivillous fibrin deposition and chronic histiocytic intervillositis are entities of unclear etiology associated with recurrent abortion and preterm birth. Autoimmune diseases and thrombophilia are occasionally associated with these pathologically defined lesions. Pregnancy-associated hypertensive disease and particularly preeclampsia as the cause of intrauterine developmental delay and elective cesarean section often show characteristic pathoanatomical placental lesions, which can give indications for the severity and duration of the disease and the prognosis for the child. Early onset (<34 weeks of gestation) and late onset preeclampsia show clinical and morphological differences. Subsequent pregnancies are classified as being at risk and screening for preeclampsia should be clinically performed. PMID- 27255228 TI - [Grading of tumors in the tubular digestive tract : Esophagus, stomach, colon and rectum]. AB - Grading of tumors located in the tubular digestive tract is an integral component of pathology assessment reports but is subordinate to the histological typing of tumors with respect to the prognostic significance. Tumor grading has not been shown to be an independent prognostic marker for most tumor entities in the gastrointestinal tract; however, it may be relevant for further routine treatment decision making in early Union Internationale Contre le Cancer (UICC) stage cancers in which the prognosis for patients is less dominated by advanced tumor spread. Owing to the more favorable prognosis of microsatellite instability in colorectal cancer, the World Health Organization (WHO) has recommended that poorly differentiated tumors should be tested and graded as low grade (G1/G2) when microsatellite instability is detected. This recommendation has been integrated into the German S3 guidelines for colorectal cancers. Accordingly, microsatellite instability testing for grading purposes should become routine practice. PMID- 27255229 TI - Transition from traditional to modern forest management shaped the spatial extent of cattle pasturing in Bialowieza Primeval Forest in the nineteenth and twentieth centuries. AB - Pasturing of livestock in forests has had profound consequences for Europe's landscapes. In Bialowieza Primeval Forest (BPF), cattle pasturing was a part of traditional forest use that ceased only in the second half of the twentieth century. We collected information on the institutional changes governing forest cattle pasturing and the changes in spatial extent of cattle presence in BPF in last two centuries and information on cattle numbers and their impact on forest regeneration. The spatial extent of cattle pasturing was highly variable, with the distribution of grazing areas frequently changing. Forest near villages (constituting less than 10 % of the area) was most often used for cattle grazing during continued longer time periods. Historical data showed that cattle have had a clear impact on forest regeneration. However, the frequent changes that occurred in the extent of cattle grazing indicate that their impact occurred locally, was smaller in other less intensively used areas, and in the forest as a whole. PMID- 27255230 TI - Multiple-factor classification of a human-modified forest landscape in the Hsuehshan Mountain Range, Taiwan. AB - Human actions drive landscape heterogeneity, yet most ecosystem classifications omit the role of human influence. This study explores land use history to inform a classification of forestland of the Tayal Mrqwang indigenous people of Taiwan. Our objectives were to determine the extent to which human action drives landscape heterogeneity. We used interviews, field sampling, and multivariate analysis to relate vegetation patterns to environmental gradients and human modification across 76 sites. We identified eleven forest classes. In total, around 70 % of plots were at lower elevations and had a history of shifting cultivation, terrace farming, and settlement that resulted in alder, laurel, oak, pine, and bamboo stands. Higher elevation mixed conifer forests were least disturbed. Arboriculture and selective harvesting were drivers of other conspicuous forest patterns. The findings show that past land uses play a key role in shaping forests, which is important to consider when setting targets to guide forest management. PMID- 27255231 TI - T11TS Treatment Augments Apoptosis of Glioma Associated Brain Endothelial Cells, Hint Toward Anti-Angiogenic Action in Glioma. AB - Malignant glioma continues to be a clinical challenge with an urgent need for developing curative therapeutic intervention. Apoptosis induction in tumor associated endothelial cells represent a central mechanism that counteracts angiogenesis in glioma and other solid tumors. We previously demonstrated that intraperitoneal administration of sheep erythrocyte membrane glycopeptide T11 target structure (T11TS) in rodent glioma model inhibits PI3K/Akt pathway and Raf/MEK/ERK signaling in glioma-associated brain endothelial cells. In the present study, we investigated whether T11TS treatment influence apoptosis signaling in vivo in glioma-associated brain endothelial cells. Annexin-V/PI staining showed that T11TS treatment in glioma-induced rats increases apoptosis of glioma-associated endothelial cells within glioma milieu compared to brain endothelial cells in glioma induced and control groups. Flowcytometric JC-1 assay revealed that T11TS administration triggers loss of mitochondrial membrane potential in glioma-associated brain endothelial cells. Flowcytometry, immunoblotting, and in situ immunofluoresecnt imaging were employed to investigate the effect of T11TS on apoptotic regulatory proteins in brain endothelial cells. T11TS treatment-upmodulated expression of p53, Bax, Fas, FasL, and FADD in glioma associated endothelial cells and downregulated Bcl-2 protein. T11TS therapy induced cytochrome-c release into cytosol, activated caspase -9, 8, 3, and cleaved Bid in glioma associated brain endothelial cells. The study demonstrates that T11TS induces apoptosis in glioma-associated brain endothelial cells via p53 accumulation and activation of intrinsic as well as Fas-dependent extrinsic pathway. The pro-apoptotic action of T11TS on glioma-associated endothelial cells provides crucial insight into how T11TS exerts its anti angiogenic function in glioma. J. Cell. Physiol. 232: 526-539, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27255232 TI - A concept analysis of women's vulnerability during pregnancy, birth and the postnatal period. AB - AIM: To report an analysis of the concept of vulnerability associated with pregnancy, birth and the postnatal period. BACKGROUND: The concept of vulnerability during childbirth is complex and the term, 'to be vulnerable' frequently attains a vague application. Analysis about vulnerability is needed to guide policy, practice, education and research. Clarity around the concept has the potential to improve outcomes for women. DESIGN: Concept analysis. DATA SOURCES: Searches were conducted in CINAHL, EMBASE, PubMed, Psychinfo, MEDLINE, MIDIRS and ASSIA and limited to between January 2000 - June 2014. Data were collected over 12 months during 2014. METHODS: This concept analysis drew on Morse's qualitative methods. RESULTS: Vulnerability during pregnancy, birth and the postnatal period can be defined by three main attributes: (a) Threat; (b) Barrier; and (c) Repair. Key attributes have the potential to influence outcome for women. Inseparable sub-attributes such as mother and baby attachment, the woman's free will and choice added a level of complexity about the concept. CONCLUSION: This concept analysis has clarified how the term vulnerability is currently understood and used in relation to pregnancy, birth and the postnatal period. Vulnerability should be viewed as a complex phenomenon rather than a singular concept. A 'vulnerability journey plan' has the potential to identify how reparative interventions may develop the woman's capacity for resilience and influence the degree of vulnerability experienced. Methodology based around complex theory should be explored in future work about vulnerability. PMID- 27255233 TI - The value of serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein as a predictive marker for hepatitis C virus-related complications after systemic chemotherapy. AB - Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA(+)-M2BP) was developed recently as a predictive marker of progression to liver fibrosis and hepatocellular carcinoma (HCC) in patients seropositive for hepatitis C virus (HCV). We retrospectively analyzed 16 HCV-seropositive patients who received systemic chemotherapy for hematologic malignancies to evaluate the usefulness of WFA(+)-M2BP for predicting HCV-related complications. These were defined as the onset of significant liver damage (LD) with increased HCV RNA levels, leading to interrupted or discontinued chemotherapy or the occurrence of HCC after chemotherapy. Baseline WFA(+)-M2BP levels were determined using preserved serum samples. The median level of WFA(+)-M2BP was 1.59 [cutoff index (C.O.I.) value range 0.38-6.66]. With a median follow-up of 623 days (range 120-2404), LD and HCC were observed in three and two patients, respectively. Detectable HCV RNA and WFA(+)-M2BP >=2.0 C.O.I. at baseline were identified as risk factors for these HCV-related complications (P = 0.034 and P = 0.005, respectively). The sensitivity, specificity, and positive and negative predictive values of the WFA(+)-M2BP level (cutoff point: 2.0 C.O.I.) for the occurrence of HCV-related complications were 100.0, 81.8, 71.4, and 100.0 %, respectively. WFA(+)-M2BP may be a useful marker for the prediction of HCV-related complications in HCV seropositive patients following systemic chemotherapy. PMID- 27255235 TI - Field Inter-Rater Reliability of the Psychopathy Checklist-Revised. AB - Strong inter-rater reliability has been established for the Hare Psychopathy Checklist-Revised (PCL-R), specifically by examiners in research contexts. However, there is less support for inter-reliability in applied settings. This study examined archival data that included a sample of sex offenders ( n = 178) who entered federal custody between 1992 and 1998. The offenders were assessed using the PCL-R on two occasions. The first assessment occurred at Millhaven Institution, the intake unit for federally incarcerated offenders in the province of Ontario. The second assessment took place upon inmates' transfer to the Regional Treatment Center, which admits federal inmates with intense psychological and psychiatric needs. Intra-class correlation coefficients (ICCs) were calculated for item, total, factor, and facet scores. The ICC absolute agreement for the PCL-R total and factor scores from raters across both settings was slightly better than what has been previously reported by Hare. Results of this study show that the reliability of PCL-R scores in field settings can be comparable to those in research settings. Authors conclude by highlighting the importance of training, consultation, considering different scores for a given item, following the guidelines of the manual in addition to considering measures that enhance neutrality and reliability of findings in the criminal justice system. PMID- 27255236 TI - The Influence of Age and Sexual Drive on the Predictive Validity of the Juvenile Sex Offender Assessment Protocol-Revised. AB - The Juvenile Sex Offender Assessment Protocol-Revised (J-SOAP-II) is the most commonly used measure in the assessment of recidivism risk among juveniles who have committed sexual offenses (JSOs), but mixed support exists for its predictive validity. This study compared the predictive validity of the J-SOAP-II across two offender characteristics, age and sexual drive, in a sample of 156 JSOs who had been discharged from a correctional facility or a residential treatment program. The J-SOAP-II appeared to be a better predictor of sexual recidivism for younger JSOs (14-16 years old) than for older ones (17-19 years old), with significant differences found for the Dynamic Summary Scale and Scale III (Intervention). In addition, several of the measure's scales significantly predicted sexual recidivism for JSOs with a clear pattern of sexualized behavior but not for those without such a pattern, indicating that the J-SOAP-II may have greater clinical utility for JSOs with heightened sexual drive. The implications of these findings are discussed. PMID- 27255234 TI - Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats. AB - Vitamin D has an anabolic effect on bone developmental processes and is involved in maintaining skeletal integrity. In recent years, pediatric cases of vitamin D intoxication have attracted attention. Therefore, the aim of this study was to investigate the influence of long-term administration of physiologically-high dose calcitriol (1,25(OH)2D3) on bone remodeling in young developing rats. Neonatal rats received once-daily subcutaneous injection of calcitriol (250 ng/kg body weight), or PBS only as a control, for 3 weeks. At 1, 2 and 4 weeks' post administration, rats were sacrificed and fixed by transcardial perfusion with 4 % paraformaldehyde, following which tibiae were extracted for histochemical analysis. Compared with the control group, the number of tartrate-resistant acid phosphatase- and Cathepsin K-positive osteoclasts were significantly increased, and the expression of alkaline phosphatase in osteoblasts was decreased in trabecular bone of rats administered high-dose 1,25(OH)2D3, leading to decreased trabecular bone volume. In addition, the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) was increased, while that of osteoprotegerin was weaker in osteoblasts in the experimental group compared with the control group. Moreover, there was weaker immunoreactivity for EphrinB2 in osteoclasts and EphB4 in osteoblasts of trabecular bone in the experimental group compared with the control group. These findings suggest that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents. PMID- 27255238 TI - Phacoemulsification technology update. PMID- 27255237 TI - Evaluation of oxidative stress markers in obstructive sleep apnea syndrome and additional antioxidant therapy: a review article. AB - PURPOSE: The hypoxia and reoxygenation cycles in obstructive sleep apnea syndrome (OSAS) cause a change in the oxidative balance, leading to the formation of reactive oxygen species capable of reacting with other organic molecules impairing their functions. This study aimed to determine the best markers of oxidative stress in OSAS and what better antioxidant agent to be used to treat the disease. METHODS: Searches were conducted in three different databases (PubMed, LILACS, SCIELO), using as descriptors the terms obstructive sleep apnea, oxidative stress, and antioxidant therapy. A total of 120 articles were found but only those considered of interest to the research were selected. Thus, 10 articles were included for further analysis regarding the biomarkers of oxidative stress in OSAS, and 6 articles to evaluate the antioxidant most often used for demonstration of efficacy. RESULTS: The thioredoxin, malondialdehyde, superoxide dysmutase, and reduced iron were the most commonly used biomarkers and showed a more consistent relationship between increased oxidative stress and OSAS. As antioxidant therapy, vitamin C and N-acetylcysteine (NAC) presented interesting results as a reduction of oxidative stress, which may become an alternative to the complementary treatment of OSAS. CONCLUSIONS: This review's findings agree mostly to measure that the markers of oxidative stress in OSAS may be a contributing aspect to assessment and monitoring of patient, and the antioxidant therapy appears to be beneficial in the treatment of OSAS. PMID- 27255239 TI - Management of subluxated capsular bag-fixated intraocular lenses using a capsular anchor. AB - We describe the use of the capsular anchor (AssiAnchor) to manage a subluxated intraocular lens (IOL) in the capsular bag. The anchor comprises 2 prongs that hold the anterior lens capsule and a central rod that is sutured to the scleral wall, enabling centration of the IOL-capsular bag complex. Six pseudophakic patients presenting with subluxated posterior chamber IOLs in the capsular bag were operated on using the device. The anchor was used successfully in all cases, although in 2 cases only 1 prong was placed under the capsulorhexis edge. In 1 eye, 2 anchors were used 1 month apart following repeated traumatic zonular injury. The capsular bag holding the IOL remained centered and stable throughout the follow-up period. The anchoring device, which was originally designed to preserve the lens capsule and stabilize subluxated crystalline lenses, can also be used to treat subluxation of a capsular bag-fixated IOL. FINANCIAL DISCLOSURE: Dr. Assia is the inventor of the AssiAnchor, has a licensed patent of the anchor, and is consultant to Hanita Lenses. Dr. Lapid-Gortzak is a consultant to and speaker for Alcon Surgical, Inc., Hanita Lenses, Orca Surgical, and Sanoculis Ltd.; a speaker for Santen; and a consultant to Icon. Drs. Ton and Naftali have no financial or proprietary interest in any material or method mentioned. PMID- 27255240 TI - Near-point string: Simple method to demonstrate anticipated near point for multifocal and accommodating intraocular lenses. AB - We present a technique that uses a near-point string to demonstrate the anticipated near point of multifocal and accommodating intraocular lenses (IOLs). Beads are placed on the string at distances corresponding to the near points for diffractive and accommodating IOLs. The string is held up to the patient's eye to demonstrate where each of the IOLs is likely to provide the best near vision. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255241 TI - New regression formula for toric intraocular lens calculations. AB - PURPOSE: To evaluate and compare the accuracy of 2 toric intraocular lens (IOL) calculators with or without a new regression formula. SETTING: Ein-Tal Eye Center, Tel-Aviv, Israel, and the Lions Eye Institute, Nedlands, Western Australia, Australia. DESIGN: Retrospective case series. METHODS: A new regression formula (Abulafia-Koch) was developed to calculate the estimated total corneal astigmatism based on standard keratometry measurements. The error in the predicted residual astigmatism was calculated by the Alcon and Holladay toric IOL calculators with and without adjustments by the Abulafia-Koch formula. These results were compared with those of the Barrett toric calculator. RESULTS: Data from 78 eyes were evaluated to validate the Abulafia-Koch formula. The centroid errors in predicted residual astigmatism were against-the-rule with the Alcon (0.55 diopter [D]) and Holladay (0.54 D) toric calculators and decreased to 0.05 D (P < .001 [x-axis], P = .776 [y-axis]) and 0.04 D (P < .001 [x-axis], P = .726 [y-axis]) with adjustments by the Abulafia-Koch formula. The Alcon and the Holladay toric calculators had a higher proportion of eyes within +/-0.50 D of the predicted residual astigmatism with the Abulafia-Koch formula (76.9% and 78.2%, respectively) than without it (both 30.8%). There were no significant differences between the results of the Abulafia-Koch-modified Alcon and the Holladay toric calculators and those of the Barrett toric calculator. CONCLUSION: Adjustment of commercial toric IOL calculators by the Abulafia-Koch formula significantly improved the prediction of postoperative astigmatic outcome. FINANCIAL DISCLOSURE: Dr. Abulafia received a speaker's fee from Haag-Streit AG. Dr. Barrett has licensed the Barrett Toric Calculator to Haag-Streit AG. Dr. Koch is a consultant to Alcon Laboratories, Inc., Abbott Medical Optics, Inc., and Revision Optics, Inc. Dr. Hill is a paid consultant to Haag-Streit AG and Alcon Laboratories, Inc. None of the other authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255242 TI - Comparison of a new image-guided system versus partial coherence interferometry, Scheimpflug imaging, and optical low-coherence reflectometry devices: Keratometry and repeatability. AB - PURPOSE: To determine the repeatability of keratometry of the Verion image-guided system and to compare the keratometry (K) values with those of established biometric devices. SETTING: International Vision Correction Research Centre, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany. DESIGN: Prospective case series. METHODS: One randomly chosen eye of volunteers was examined with partial coherence interferometry (PCI) (IOLMaster 500), optical low-coherence reflectometry (OLCR) (Lenstar LS 900), a Scheimpflug device (Pentacam HR), and the new image-guided system by the same examiner. None of the eyes had ocular pathology. Three consecutive measurements were performed with the image-guided system and 1 with the other devices. The flat, steep, and average corneal radii; steep axis; and white-to-white (WTW) distance were analyzed and compared. RESULTS: One hundred twenty-three eyes of 123 volunteers (mean age 37.9 years +/- 16.2 [SD]) had valid measurements for all examinations and were available for analysis. The image-guided system measured statistically significant smaller flat, steep, and average corneal radii than the Scheimpflug device, statistically significant larger flat and average corneal radii than the PCI device, and no statistically significant different values than the OLCR device. The measured steep axis did not differ significantly in any comparison. The WTW measurements were significantly higher than those of all other devices. The analysis of repeatability of the image-guided system showed high intraclass correlation coefficients (range 0.919 to 0.997). CONCLUSIONS: The new image guided system had high repeatability for K, steep axis, and WTW measurements. The WTW measurements with the image-guided system were significantly higher than those using the other devices. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255243 TI - Agreement of anterior ocular biometric measurements with a new optical biometer and a Scheimpflug tomographer. AB - PURPOSE: To evaluate the agreement between a new optical biometer (AL-Scan) and an anterior-segment Scheimpflug tomographer (Pentacam HR). SETTING: Eye Hospital of Wenzhou Medical University, Zhejiang, China. DESIGN: Prospective randomized comparative case series. METHODS: Three consecutive scans of the right eye of each subject were obtained using each device in a random order. The following common parameters were recorded: central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth, and keratometry (K) readings (steep, flat, and mean). Bland-Altman limits of agreement (LoA) were calculated for the common device parameters. RESULTS: The study comprised 121 healthy subjects (57 men, 64 women) with a mean age of 25.41 years +/- 6.86 (SD) (range 18 to 54 years). The mean difference in CCT was 1.61 MUm with LoA of -6.29 to 9.52 MUm. The mean difference in the aqueous depth and ACD was 0.02 mm with LoA of -0.10 to 0.14 mm and -0.09 to 0.14 mm, respectively. For the 2.4 mm K readings from the new biometer versus the standard K readings from the Scheimpflug tomographer, the mean difference for flat K, steep K, and mean K was 0.10 diopter (D), 0.05 D, and 0.08 D, respectively. The LoA were -0.17 to 0.38 D, -0.29 to 0.39 D, and -0.19 to 0.34 D, respectively. The CCT, ACD, and all K readings were assessed to be clinically interchangeable. CONCLUSION: There was good agreement between the 2 devices for CCT, ACD, aqueous depth, and K readings. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255244 TI - Comparative analysis of optical biometers. AB - PURPOSE: To evaluate the level of agreement, repeatability, and correlation of 2 optical biometers, the IOLMaster (based on partial coherence interferometry [PCI]) and Aladdin (based on optical low-coherence interferometry [OLCI]) in terms of axial length (AL), mean keratometry (K), anterior chamber depth (ACD), and corneal diameter. SETTING: Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. DESIGN: Prospective comparative case series. METHODS: Each participant had biometry with both biometers. The level of agreement between the biometers was calculated using the Bland-Altman method. Double-angle polar plots were used to display the astigmatism vectors. Internal consistency was computed with the Cronbach alpha coefficient of reliability, whereas the dispersion of probability distribution was assessed with the coefficient of variation (CoV). The intraoperator repeatability was analyzed using the intraclass correlation coefficient (ICC); the AL was evaluated in all eyes and the mean K and the ACD in a subset of eyes. RESULTS: The study comprised 215 eyes; the ICC for the mean K and ACD was calculated in a subset of 54 eyes. There was a statistically significant difference between the 2 biometers in all measurements (P < .05). The level of agreement was high with both methods. The ICC and internal consistency were excellent with both biometers; the CoVs were low. CONCLUSIONS: The OLCI biometer provided good agreement and repeatability compared with the PCI biometer, the current gold standard in ocular biometry. Further comparative studies are necessary to clearly define the role of the OLCI biometer in predicting postoperative refractive outcomes. FINANCIAL DISCLOSURES: Dr. Findl is a scientific advisor to Carl Zeiss Meditec AG. None of the other authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255245 TI - Evaluation of intraocular lens position during phacoemulsification using intraoperative spectral-domain optical coherence tomography. AB - PURPOSE: To assess the position of intraocular lenses (IOLs) at the end of standard phacoemulsification with intraoperative spectral-domain optical coherence tomography (SD-OCT). SETTINGS: Department of Ophthalmology, Rudolf Foundation Hospital, Vienna, Austria. DESIGN: Prospective case series. METHODS: Standard phacoemulsification with IOL implantation was performed. The Rescan 700 SD-OCT system was used for intraoperative imaging. The anterior segment of the eye was scanned using SD-OCT at the end of the surgery. The distance from the IOL optic center and the IOL optic edge to the posterior capsule was measured postoperatively using graphic software. RESULTS: The study comprised 74 patients (101 eyes). The mean axial length was 23.97 mm (range 21.43 to 28.61 mm). The mean IOL power was 20.39 diopters (D) (range 6.5 to 27.5 D). Contact between the IOL and posterior capsule was absent in 88 cases (87.13%), and partial or full contact was present in 13 cases (12.87%). The mean distance between the IOL central optic and posterior capsule was 0.71 pixel (range 0.06 to 1.38 pixels) in 99 cases (98.02%). In 42 cases (57.53%), partial contact between the IOL edges and the posterior capsule was noticed. The mean distance between the IOL edge and posterior capsule was 0.21 pixel (range 0.04 to 0.92 pixel). CONCLUSIONS: Intraoperative SD-OCT facilitated the imaging of IOL position during standard phacoemulsification. Contact between the IOL central optic and posterior capsule at the end of the surgery occurred rarely. Improved IOL design should be considered. FINANCIAL DISCLOSURE: Drs. Binder and Glittenberg are consultants to Carl Zeiss Meditech AG. None of the other authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255246 TI - Relationship of corneal asphericity to intraocular lens power calculations after myopic laser in situ keratomileusis. AB - PURPOSE: To examine whether corneal asphericity affects underestimation in the SRK/T intraocular lens (IOL) power calculation after myopic laser in situ keratomileusis (LASIK) and to evaluate the predictability of IOL power underestimation using the asphericity. SETTING: Kitasato University, Kanagawa, and Miyata Eye Hospital, Miyazaki, Japan. DESIGN: Retrospective case series. METHODS: The clinical records of eyes that had IOL implantation during cataract surgery after previous myopic LASIK between May 2008 and October 2014 were reviewed. For eyes with an available clinical history, the effect of manifest refraction spherical equivalent before LASIK, axial length, and the asphericity (Q value) on cataract surgery and the refractive error in the use of the SRK/T formula were examined using stepwise multiple regression analysis. Predictions with the resultant regression equation and significant factors were evaluated with Bland-Altman plots. RESULTS: Fifty-four eyes of 37 patients were included. The mean duration from LASIK to cataract surgery was 9.1 years +/- 3.5 (SD) (range 2 to 14 years). Multiple regression analysis using 22 eyes of 22 patients resulted in a significant factor, which was the Q value (P < .001, R(2) = 0.80). The refractive errors in 53 eyes were predicted with tolerances of 64.5% and 87.0% within +/-0.5 diopter (D) and within +/-1.0 D, respectively. Bland-Altman analysis showed that 95% of the limitation range was 2.59 D. CONCLUSIONS: The corneal asphericity after myopic LASIK significantly correlated with the IOL power underestimation with use of the SRK/T formula. The refractive error could also be predicted well with the use of asphericity. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255247 TI - Risk factors for early-onset corneal haze after photorefractive keratectomy in an Asian population: Outcomes from the Singapore Armed Forces Corneal Refractive Surgery Programme 2006 to 2013. AB - PURPOSE: To assess the incidence and risk factors for early corneal haze after myopic photorefractive keratectomy (PRK). SETTING: Tertiary eye center, Singapore. DESIGN: Retrospective case series. METHODS: The refractive results and corneal haze severity 3 months after PRK were analyzed. Eyes were categorized into 4 groups based on haze severity. Multivariate ordinal logistic regression analysis adjusting for age, ethnicity, sex, use of intraoperative mitomycin-C (MMC), preoperative sphere, and preoperative cylinder was performed. RESULTS: The study reviewed data from 177 patients (347 eyes) with a mean age of 22.6 years +/ 4.1 (SD). The majority of the patients were Chinese (98.3%) and men (98.3%). The mean preoperative spherical equivalent (SE) was -3.34 +/- 1.19 diopters (D). One hundred thirty-five eyes (38.9%) had PRK with MMC. Ten eyes (2.9%) had enhancement surgery. The overall efficacy index was 0.88 and the safety index was 1.07. At 3 months, 187 eyes (53.9%) had no haze, 76 eyes (21.9%) had a haze grade of more than 0 and less than 1, 76 eyes (21.9%) had a haze grade of 1 or more and less than 2, and 8 eyes (2.3%) had grade 2 haze. Higher degrees of myopia (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.13-1.63; P = .001) and astigmatism (OR, 1.56; 95% CI, 1.09-2.24; P = .014) were associated with increased severity of corneal haze, whereas older age (OR, 0.94; 95% CI, 0.88 0.99; P = .023) had a protective effect. CONCLUSION: Myopia and astigmatism were associated with increased severity of haze, and older age was protective against early corneal haze development after PRK in an Asian population. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255248 TI - Sixteen-year follow-up of hyperopic laser in situ keratomileusis. AB - PURPOSE: To assess the long-term efficacy and safety of hyperopic laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom. DESIGN: Prospective cohort study. METHODS: Hyperopic LASIK was performed using a mechanical microkeratome, an optical zone of 6.5 mm, and a blend zone of 1.5 mm. Simple hyperopia was treated. RESULTS: The mean patient age was 51.6 years (range 34 to 60 years). Preoperatively, the mean spherical equivalent (SE) was +3.74 diopters (D) (range +1.25 to +6.50 D). The mean attempted correction was +3.64 D (range +1.5 to +6.0 D). The mean follow-up was 16.5 years. The mean SE was +0.28 D (range -1.0 to +1.5 D) at 12 months, +0.84 D (range -0.75 to +3.35 D) at 5 years, and +1.74 D (range -0.75 to +4.13 D) at 16 years, representing an increase in hyperopia of +1.47 D +/- 1.43 (SD) between 1 year and 16 years (P < .0001) and of +1.13 +/- 0.8 D between 5 years and 16 years (P < .03). The uncorrected distance visual acuity improved at 16 years (P < .0001); corrected distance visual acuity (CDVA) was unchanged (P < .2). The efficacy index was 0.5 and the safety index, 1.09. One eye (3%) lost 2 lines of CDVA. Keratometry remained stable between 1 year and 16 years (P < 1.0). Four eyes (12%) had cataract surgery, and 2 (6%) had laser iridotomy. There was no ectasia. CONCLUSIONS: After hyperopic LASIK, an increase in hyperopia occurred between 1 and 5 years and 16 years. At 16 years, efficacy was limited but with no sight-threatening complications. FINANCIAL DISCLOSURES: Dr. Marshall was a consultant to Summit Technology, Inc. Dr. O'Brart holds a noncommercial research grant from Alcon Laboratories, Inc. None of the other authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255249 TI - Nanosecond laser-assisted cataract surgery: Endothelial cell study. AB - PURPOSE: To evaluate corneal endothelial cell density (ECD) and morphology after cataract surgery using coaxial ultrasound (US) phacoemulsification or a recently introduced coaxial nanosecond laser technique. SETTING: Department of Ophthalmology, Medical University of Sofia, Sofia, Bulgaria. DESIGN: Prospective cohort study. METHODS: Coaxial US phacoemulsification was performed in 1 eye (US group) and coaxial nanosecond laser-assisted cataract surgery in the contralateral eye (laser group) of the same patient. Nuclear sclerosis was graded from nuclear opalescence (NO) 3, nuclear color (NC) 3 to NO4, NC4 using the Lens Opacities Classification System III. The central ECD, coefficient of variation (CoV) in cell size (objective measure of polymegethism), and percentage of hexagonal cells (an index of pleomorphism) were evaluated. RESULTS: Eighty-two eyes (41 patients) had uneventful surgery. The mean ECD was 2517 cells/mm(2) +/- 137 (SD) preoperatively and 2287 +/- 155 cells/mm(2) at 2 years in the US group and 2521 +/- 233 cells/mm(2) and 2420 +/- 292 cells/mm(2), respectively, in the laser group (both P < .001). The mean CoV was 0.27 +/- 2.4 preoperatively and 0.30 +/- 2.4 at 2 years in the US group and 0.27 +/- 2.8 and 0.27 +/- 2.0, respectively, in the laser group (both P < .001). The mean percentage of hexagonal cells was 42.3% +/- 3.6% preoperatively and 37.74% +/- 3.54% at 2 years in the US group and 42.8% +/- 3.2% and 43.00% +/- 2.68%, respectively, in the laser group (both P < .001). CONCLUSION: Nanosecond laser phacoemulsification had advantages over US phacoemulsification in terms of endothelial cell structure preservation. FINANCIAL DISCLOSURES: Dr. Kanellopoulos is consultant to Alcon Surgical, Inc., Allergan, Inc., Avedro, Inc., Keramed, Inc., Optovue, Inc., i Optics Corp., and Carl Zeiss Meditec AG. Neither of the other authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255250 TI - Fourier analysis of videokeratography data: Clinical usefulness in grade I and subclinical keratoconus. AB - PURPOSE: To evaluate the contribution of Fourier analysis of videokeratographic data in the diagnosis of subclinical keratoconus and keratoconus. SETTING: Eye Institute of Thrace, Democritus University, Alexandroupolis, Greece. DESIGN: Observational case series. METHODS: The following Pentacam-derived parameters, resulting from Fourier decomposition of keratometric data, were evaluated for their diagnostic capacity using receiver operating curves: spherical component and eccentricity, maximum decentration, regular astigmatism in the center and in the periphery, mean astigmatism, irregularities, regular astigmatism in the center plus the irregularities, and total astigmatism. Logistic regression was performed to identify a combined diagnostic model. RESULTS: The study comprised 80 keratoconus eyes, 55 eyes diagnosed with subclinical keratoconus, and 50 normal eyes. Significant differences were detected in spherical eccentricity, maximum decentration, irregularities, regular astigmatism in the center and in the periphery, regular astigmatism in the center plus the irregularities, mean astigmatism, and total astigmatism parameters between the groups. Almost all parameters had high diagnostic ability in both study groups (area under the curve >90%). Among individual parameters, those with the highest predictive accuracy were the regular astigmatism in the center plus the irregularities (subclinical keratoconus 97.6%, keratoconus 98.8%) and the maximum decentration (subclinical keratoconus 91.4%, keratoconus 98.5%). Sufficient predictive accuracy (subclinical keratoconus 99.4, keratoconus 100%) was identified in a diagnostic model that combined the regular astigmatism in the center plus the irregularities and the maximum decentration. CONCLUSION: Fourier decomposition of keratometric data provided parameters with high accuracy in differentiating corneas with subclinical keratoconus from normal corneas and should be included to allow prompt diagnosis of keratoconus. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255251 TI - Epithelium-on corneal collagen crosslinking for management of advanced keratoconus. AB - PURPOSE: To report the 1-year visual and keratometric results of epithelium-on corneal collagen crosslinking (CXL) for advanced keratoconus (median maximum keratometry [K] >=58.0 diopters [D]). SETTING: School of Ophthalmology and Optometry and Eye Hospital of Wenzhou Medical College, Wenzhou, China. DESIGN: Prospective case series. METHODS: Patients with bilateral progressive keratoconus had tetracaine-enhanced epithelium-on CXL. The worse eye had CXL, and the fellow eye was not treated. Results were reported 1, 3, 6, and 12 months postoperatively. The outcomes were compared with those in the fellow untreated eyes. RESULTS: Twenty-one eyes of 21 patients with a median age of 20.4 years (interquartile range [IQR], 9.5 years) were treated. A significant improvement in postoperative uncorrected distance visual acuity was observed at 12 months (P = .002). Postoperative corrected distance visual acuity improved at 6 months and 12 months (P <= .009) compared with baseline values. The maximum K decreased by 1.63 D from the median preoperative maximum K of 62.7 D (IQR, 12.9 D) at 12 months (P < .001). The reduction in maximum K was higher after CXL than in untreated eyes at the end of 12 months (P = .001). Correlation analysis between the preoperative maximum K values and the change over 6 to 12 months between different studies showed a significant correlation (r = -0.764, P < .001; Spearman correlation). CONCLUSIONS: Epithelium-on CXL was an effective treatment for patients with advanced keratoconus. A higher preoperative maximum K value correlated with greater corneal flattening after CXL. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255252 TI - Impact of botulinum toxin-A on corneal curvature assessed with Scheimpflug and Placido systems. AB - PURPOSE: To evaluate the effect of eyelid spasm treatment with botulinum toxin-A (BTX-A) on corneal curvature assessed with Scheimpflug (Pentacam) and Placido (Atlas) systems. SETTING: Federal University of Sao Paulo, Sao Paulo, Brazil. DESIGN: Prospective interventional case series. METHODS: Patients with hemifacial spasm were evaluated. Steep keratometry (K) and corneal astigmatism (magnitudes and treatment-induced astigmatism) obtained with the Placido and Scheimpflug systems were evaluated before BTX-A application and after 15 days and 2, 3, and 4 months. RESULTS: The study evaluated 48 eyes (24 affected and 24 normal contralateral eyes) of 24 patients. The mean steep K and astigmatism values obtained with the Placido system on the affected side before treatment were 46.91 diopters (D) +/- 3.57 (SD) and 2.63 +/- 2.46 D, respectively. A significant decrease in steep K (45.14 +/- 1.20 D) and astigmatism (1.01 +/- 0.58 D) was observed 2 months (P = .003 and P = .0004, respectively) and 3 months (45.64 +/- 1.77 D and 1.36 +/- 1.31 D, respectively) (P = .03 and P = .01, respectively) after treatment. The Scheimpflug system did not show significant changes in steep K measurements during the 4-month period. The mean astigmatism in the affected eye before treatment was 1.27 +/- 0.88 D. A significant reduction was observed at 15 days (1.16 +/- 1.16 D) and at 4 months (0.91 +/- 0.59 D) (P = .02 and P = .03, respectively). CONCLUSION: The Placido system was more sensitive in detecting a temporary reduction in corneal curvature after eyelid-spasm treatment. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255254 TI - Intraocular pressure study using monitored forced-infusion system phacoemulsification technology. AB - PURPOSE: To optimize phacoemulsification efficiency by varying the intraocular pressure (IOP) using the Centurion Vision System, a monitored forced-infusion system. SETTING: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Laboratory investigation. METHODS: Porcine lenses were soaked in formalin and divided into 2.0 mm cubes; 0.9 mm balanced tips were used. Intraocular pressure levels were tested from 30 to 110 mm Hg at 10 mm Hg intervals. Vacuum was set at 500 mm Hg, aspiration at 35 mL/min, and torsional power at 60%. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were measured. RESULTS: There was a linear relationship between efficiency and IOP. Increasing IOP led to an increase in efficiency (ie, to a decrease in time necessary to remove the lens fragment) (R(2) = .5769, P = .0176). Chatter correlated with IOP in the range of 30 to 50 mm Hg (R(2) = .4506, P = .0448) and was minimal at higher IOPs. CONCLUSIONS: Increasing IOP in the monitored forced-infusion system improved efficiency. Chatter was also decreased or eliminated with increasing IOP. Additional studies will be required to understand the reasons for these findings. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255253 TI - Congenital cataract surgery without intraocular lens implantation in persistent fetal vasculature syndrome: Long-term clinical and functional results. AB - PURPOSE: To evaluate long-term clinical and functional outcomes after congenital cataract surgery in persistent fetal vasculature (PFV). SETTING: Department of Ophthalmology, Goethe-University, Frankfurt, Germany. DESIGN: Retrospective comparative case series. METHODS: The records of eyes with congenital cataract associated or not associated with PFV that had cataract surgery without intraocular lens (IOL) implantation within the first 18 months of life were reviewed. Long-term visual outcomes and clinical parameters, including aphakic glaucoma, posterior capsule opacification (PCO), vitreous and anterior segment hemorrhage, retinal detachment (RD), and fibrin reaction, were evaluated. RESULTS: Congenital cataract was associated with PFV in 19 eyes (19 children) and not associated in 69 eyes (40 children). Sixteen patients had isolated anterior PFV; 3 eyes were classified as combined anterior and posterior PFV. The mean follow-up was 53.21 months. Postoperative visual acuity improvement was recorded in 68.4% of PFV-associated cataract eyes with a corrected visual acuity up to 20/100. Long-term visual outcomes in PFV-associated cataract eyes were significantly worse than in the 11 unilateral cataract eyes without additional PFV (P = .0067). The presence of PFV was strongly associated with a long-term increased risk for postoperative hemorrhage (P = .0001) and RD (P = .009) after primary cataract surgery and secondary IOL implantation. The prevalence of aphakic glaucoma, PCO, and fibrinous reaction was similar between PFV cataract eyes and controls. CONCLUSIONS: In most cases of PFV-associated congenital cataract, postoperative visual acuity improvement is possible. However, congenital cataract eyes associated with PFV have a long-term increased risk for postoperative hemorrhage and RD. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255255 TI - Qualitative and quantitative analyses of stroke dynamics and microfluidics of phacoemulsification probes operating in different modes. AB - PURPOSE: To compare phacoemulsification (phaco) tip movement, microfluidic dynamics, and tip-to-load interaction between longitudinal, torsional, and elliptical ultrasound (US) modalities. SETTING: Phacodynamics Laboratory, Clinica Oftalmologica, Pasteur, Santiago, Chile. DESIGN: Experimental study. METHODS: All experiments were performed using a fluid-filled optical test chamber and phaco tips that were US power activated. Tip movement was evaluated using stroke tracing and stroboscopy imaging techniques. Qualitative and quantitative assessments of microfluidic behavior were performed using bead seeding and high speed shadowgraphy imaging combined with particle-image velocimetry and vector analysis. Material load interaction was measured using a rubber sphere that represented lens material. RESULTS: Longitudinal and torsional US tips showed precise forward-and-backward and side-to-side (lateral) movement, respectively. Elliptical US tips scribed a 2-dimensional ellipsoid path that slightly changed in shape and orientation plane at higher powers. Longitudinal and lateral components of tip motion were evident in elliptical mode. Regular fluid flow was observed with longitudinal mode (forward-directed flow away from the aspiration port) and torsional mode (steady backflow into the aspiration port). In elliptical mode, bead repulsion, erratic bursts of acoustic streaming, oblique backflow, and areas of multidirectional flow were observed. The longitudinal mode caused the material load to bounce against the tip, whereas the torsional mode maintained a consistent load attraction. In elliptical mode, the material load rotated slightly and bounced away from the tip in irregular intervals when attraction was achieved. CONCLUSIONS: Tip movement, microfluidic behavior, and material load interaction were related within but varied across US modalities. The elliptical mode showed a movement pattern with longitudinal and lateral components and irregular microfluidic behaviors. FINANCIAL DISCLOSURE: Dr. Zacharias received research funding from Alcon Laboratories, Inc. He has no financial or proprietary interest in any material or method mentioned. PMID- 27255256 TI - Assessing the in vitro optical quality of presbyopic solutions based on the axial modulation transfer function. AB - PURPOSE: To present a metric for assessing the in vitro optical quality of rotationally symmetrical optical elements based on volume calculation under the surface defined by the axial modulation transfer function (MTF). SETTING: University of Valencia, Valencia, Spain. DESIGN: Experimental study. METHODS: The metric volume under the axial MTF was used to assess the optical quality of 2 rotationally symmetrical multifocal intraocular lenses (IOLs) within various defocus intervals (0.50 diopter [D], 0.75 D, and 1.00 D) and at various spatial frequency intervals (7.5 cycles per degree [cpd], 15.0 cpd, and 30.0 cpd). RESULTS: The far focus of the bifocal IOL yielded higher volume values at all spatial frequencies and defocus intervals than the trifocal IOL. The results for the near focus were similar for both IOLs. In addition, the trifocal IOL provided a distinct focus for intermediate vision. CONCLUSIONS: The volume under the axial MTF proved to be a useful tool for objective evaluation of multifocal IOLs. Moreover, it can be applied to evaluate the optical quality of every rotationally symmetrical IOL or optical element. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255257 TI - Bilateral cataract, crash risk, driving performance, and self-regulation practices among older drivers. AB - This comprehensive literature review summarizes published studies examining cataract and cataract surgery and driving outcomes to identify gaps in the literature that require further research. Six electronic databases were searched for articles published up to and including March 2015. Articles were reviewed if they included older drivers with cataract or drivers who had cataract surgery and at least 1 of the following driving outcomes: crash risk, driving self-regulation practices, and driving performance. There was consistent evidence that cataract negatively affects driving and that cataract surgery is beneficial to driving outcomes. Future research should examine the separate effects of first- and second-eye cataract surgery on crash risk, driving self-regulation, and driving performance. It should also determine how visual measures relate to driving performance among cataract patients so those most at risk for driving difficulties can be identified, advised, and possibly prioritized for surgery. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID- 27255258 TI - Small-incision lenticule extraction in posterior polymorphic corneal dystrophy. AB - We present the case of a 37-year-old man with posterior polymorphic corneal dystrophy who had small-incision lenticule extraction surgery to correct myopic refractive errors. The subjective refraction was -2.62 in the right eye and -2.50 -0.25 * 80 in the left eye. Slitlamp biomicroscopy revealed a band-like lesion in the corneal endothelium of the right eye. The endothelial cell count was 1745 cells/mm(2) in the right eye and 2945 cells/mm(2) in the left eye. Small-incision lenticule extraction was performed to correct the myopic refractive errors in both eyes. Twelve months after surgery, the uncorrected distance visual acuity in both eyes was 20/20 and the posterior polymorphic corneal dystrophy lesion had not progressed. The case suggests that small-incision lenticule extraction surgery can be performed successfully and safely in patients with posterior polymorphic corneal dystrophy. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned. PMID- 27255259 TI - Is the corneal stromal demarcation line depth a true indicator of corneal collagen crosslinking efficacy? PMID- 27255260 TI - Lens exchange and trabecular microbypass stent surgery to treat secondary pigmentary glaucoma resulting from a 1-piece foldable intraocular lens in the sulcus. PMID- 27255261 TI - Complications of sutured versus sutureless scleral-fixated intraocular lenses. PMID- 27255262 TI - Reply. PMID- 27255263 TI - Muslim Spirituality, Religious Coping, and Reactions to Terrorism Among Pakistani University Students. AB - Pakistani Muslim university students (N = 207) displayed Personal Distress, Public Distress, and Personal Defeat Reactions to Terrorism. All three reactions predicted poorer mental health with Personal Defeat being especially disturbed in its adjustment implications. In line with the assumptions of coping theory, scores on the Negative Religious Coping Scale correlated positively with Personal Distress and with Personal Defeat. However, Positive Religious Coping, the spirituality of Muslim Experiential Religiousness, and the Intrinsic and Extrinsic Personal Religious Orientations exhibited positive rather than the expected negative linkages with Personal Distress and Public Distress. Muslim Experiential Religiousness moderated associations of Positive and Negative Religious Coping with Public Distress. When spirituality was high, these relationships were negative. When spirituality was low, they became positive. These data documented the negative impacts that terrorism can have on Pakistanis and suggested that Muslim religious commitments may have an important role to play in resisting those influences. PMID- 27255264 TI - Persistent Renal Dysfunction After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction. AB - We determined the incidence, predictors, and outcomes of persistent renal dysfunction (PRD) following percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Among 16 264 patients enrolled in a nationwide registry, we studied patients with AMI who had their estimated glomerular filtration rate at baseline and 1 month later (n = 3606). We used multivariate regression and propensity score (PS)-matched Cox proportional hazards to evaluate the association between PRD and outcomes. Persistent renal dysfunction occurred in 1333 (37%) patients. Significant PRD contributors included old age, low body mass index (BMI), hypertension, Killip class, and the extent of vessel disease. Persistent renal dysfunction was associated with an increased 1-year major adverse cardiac events (all-cause death, myocardial infarction, or revascularization) relative to no-PRD (entire cohort: 6.2% vs 4.5%, hazard ratio[HR] 1.63, 95% confidence interval [CI] 1.18-2.25, P = .003; PS matched cohort: 7.2% vs 4.9%, HR 1.67, 95% CI 1.08-2.58, P = .022). In conclusion, PRD occurred in approximately one-third of patients with AMI following PCI. It was associated with old age, hypertension, low BMI, initial hemodynamic instability, and extent of vessel disease and was a predictor of worse outcomes at 1 year. PMID- 27255265 TI - Implications of a History of Syncope in Patients Hospitalized With Heart Failure. AB - We assessed the frequency and implications of a history of syncope of up to 1 year prior to hospitalization with acute heart failure (AHF) between February and November 2012. Data were collected for 5005 patients hospitalized with AHF and analyzed and compared according to the absence/presence of a history of syncope (group 1 vs group 2). Prior syncope among patients with heart failure was 5.3%. Age, gender, hypertension, atrial fibrillation, bundle branch block, left ventricular ejection fraction (LVEF), and obstructed coronary vessels were comparable in the 2 groups. Group 2 patients were more likely to smoke or have diabetes mellitus, stroke, and cardiac arrest. Group 2 patients frequently required aggressive treatment and had more worse in-hospital and 1-year outcomes compared to group 1. After adjustment for age, sex, ethnicity, and LVEF, multivariate regression analysis showed that history of syncope predicted in hospital mortality (odds ratio: 2.61; 95% confidence interval: 1.707-4.002). History of syncope during the year prior to the index admission with AHF is a marker of worse outcomes regardless of patient age and LVEF. Further studies are required to confirm this observation and its clinical implications. PMID- 27255268 TI - Attempting to Honor Beliefs of Jehovah's Witnesses at the Edge of Viability in an Infant Born at 23 Weeks' Gestational Age. AB - BACKGROUND: Infants born at 23 weeks' gestation have a poor prognosis and require intensive care, including blood transfusions, to survive. Generally speaking, the decision to forgo life support is acceptable. Jehovah's Witnesses believe that life is sacred and want lifesaving interventions except for blood transfusions. Therefore, an ethical dilemma exists when a baby is born on the edge of viability to parents that are Jehovah's Witnesses. In this case, if parents and healthcare professionals disagree on the best interests of the child, the medical team should obtain a court order from the state to intervene. CASE REPORT: We present the case of an infant born at 23 weeks' gestation to parents who are Jehovah's Witnesses. The parents wanted full life-support, except for blood transfusions, to be given. The clinical team obtained a court order to transfuse the infant. The infant unfortunately died despite all efforts. CONCLUSIONS: Currently, it is nearly impossible to honor the beliefs of Jehovah's Witnesses to provide lifesaving treatments without blood transfusions for infants born at the border of viability. If the goal is to prolong life, the standard of care for a premature infant is for a doctor to obtain a court order to override the beliefs and wishes of Jehovah's Witness parents and transfuse blood products as medically indicated. Although bloodless techniques for high-risk surgeries are under development, care for premature infants at 23 weeks' gestation necessitates red cell transfusions. PMID- 27255266 TI - Evaluation of the "Pipeline" for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research. AB - Cocaine use disorder is a persistent public health problem for which no widely effective medications exist. Self-administration procedures, which have shown good predictive validity in estimating the abuse potential of drugs, have been used in rodent, nonhuman primate, and human laboratory studies to screen putative medications. This review assessed the effectiveness of the medications development process regarding pharmacotherapies for cocaine use disorder. The primary objective was to determine whether data from animal and human laboratory self-administration studies predicted the results of clinical trials. In addition, the concordance between laboratory studies in animals and humans was assessed. More than 100 blinded, randomized, fully placebo-controlled studies of putative medications for cocaine use disorder were identified. Of the 64 drugs tested in these trials, only 10 had been examined in both human and well controlled animal laboratory studies. Within all three stages, few studies had been conducted for each drug and when multiple studies had been conducted conclusions were sometimes contradictory. Overall, however, there was good concordance between animal and human laboratory results when the former assessed chronic drug treatment. Although only seven of the ten reviewed drugs showed fully concordant results across all three types of studies reviewed, the analysis revealed several subject-related, procedural, and environmental factors that differ between the laboratory and clinical trial settings that help explain the disagreement for other drugs. The review closes with several recommendations to enhance translation and communication across stages of the medications development process that will ultimately speed the progress toward effective pharmacotherapeutic strategies for cocaine use disorder. PMID- 27255269 TI - Patterns of User Engagement with Mobile- and Web-Delivered Self-Care Interventions for Adults with T2DM: A Review of the Literature. AB - Technology-delivered interventions can improve the health behaviors and clinical outcomes of persons with diabetes, but only if end users engage with these interventions. To summarize the current knowledge on engagement with technology based interventions, we conducted a review of recent mobile- and web-delivered intervention studies for adults with type 2 diabetes published from 2011 to 2015. Among 163 identified studies, 24 studies satisfied our inclusion criteria. There was substantial variation in how intervention engagement was reported across studies. Engagement rates were lower among interventions with a longer duration, and engagement decreased over time. In several studies, older age and lower health literacy were associated with less engagement, and more engagement was associated with intervention improvement in at least one outcome, including glycemic control. Future technology-based intervention studies should report on engagement, examine and report on associations between user characteristics and engagement, and aim to standardize how this is reported, particularly in longer trials. PMID- 27255270 TI - Tolerance to the Intestinal Microbiota Mediated by ROR(gammat)(+) Cells. AB - Harmless microbes colonizing the gut require the establishment of a well equilibrated symbiosis between this microbiota and its host. However, the immune system is primed to recognize both conserved microbial patterns and foreign antigens, and therefore developed strong tolerance mechanisms to prevent potential fatal immune reactivity to symbiotic microbes. The transcription factor RAR-related orphan-like gammat [ROR(gammat); encoded by Rorc] plays a key role in the gut for lymphoid tissue organogenesis, development of innate lymphoid cells type 3 (ILC3s) and proinflammatory type 17 T helper (Th17) cells. Surprisingly, recent research has revealed a contribution of ROR(gammat)-expressing cells in a variety of tolerance mechanisms in both the innate and adaptive immune system. PMID- 27255272 TI - Intending, hastening and causing death in non-treatment decisions: a physician interview study. AB - PURPOSE: To explore how physicians analyse their non-treatment decisions in light of the concepts of hastening, causing and intending the patient's death. METHODS: Sixteen Norwegian physicians from relevant specialties were interviewed and the results analysed by systematic text condensation, a qualitative analysis framework. RESULTS: The physicians' chief dilemma in non-treatment decisions was the attempt to achieve the proper balance for the level of treatment at life's end. Respondents framed their challenges in medical and not ethical terms. They treated the concepts of intending, hastening and causing the patient's death as alien to their practical deliberations and, for many, irrelevant to the moral appraisal of their end-of-life practices. CONCLUSIONS: The core concepts of traditional medico-ethical analyses of end-of-life decision-making do not map the practical terrain well. Research on physician intentions must be designed and interpreted in light of this. PMID- 27255271 TI - High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes. AB - BACKGROUND: Early detection of oral squamous cell carcinomas (OSCCs) is urgently needed to improve the prognosis and quality of life (QOL) of patients. Oral leukoplakias (OLs), known as the most common premalignant lesions in the oral cavity, often precede OSCCs. Especially, OLs with dysplasia are known to have a high risk of malignant transformation. Here, we searched for the promoter methylation characteristic of high-risk OLs. METHODS: To identify methylation silenced genes, a combined analysis of methylated DNA immunoprecipitation (MeDIP) - CpG island (CGI) microarray analysis and expression microarray analysis after treatment with a demethylating agent was performed in two OSCC cell lines (Ca9-22 and HSC-2). The methylation statuses of each gene were examined by methylation specific PCR. RESULTS: A total of 52 genes were identified as candidates for methylation-silenced genes in Ca9-22 or HSC-2. The promoter regions of 13 genes among the 15 genes randomly selected for further analysis were confirmed to be methylated in one or more of five cell lines. In OSCC tissues (n = 26), 8 of the 13 genes, TSPYL5, EGFLAM, CLDN11, NKX2-3, RBP4, CMTM3, TRPC4, and MAP6, were methylated. In OL tissues (n = 24), seven of the eight genes, except for EGFLAM, were found to be methylated in their promoter regions. There were significantly greater numbers of methylated genes in OLs with dysplasia than in those without dysplasia (p < 0.0001). CONCLUSIONS: OLs at high risk for malignant transformation were associated with aberrant promoter methylation of multiple genes. PMID- 27255267 TI - Epilepsy, Antiepileptic Drugs, and Aggression: An Evidence-Based Review. AB - Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases. PMID- 27255273 TI - The implausibility of response shifts in dementia patients. AB - Dementia patients may express wishes that do not conform to or contradict earlier expressed preferences. Our understanding of the difference between their prior preferences and current wishes has important consequences for the way we deal with advance directives. Some bioethicists and gerontologists have argued that dementia patients change because they undergo a 'response shift'. In this paper we question this assumption. We will show that proponents of the response shift use the term imprecisely and that response shift is not the right model to explain what happens to dementia patients. We propose a different explanation for the changed wishes of dementia patients and conclude that advance directives of dementia patients cannot be simply put aside. PMID- 27255274 TI - Fatty acid and metabolomic profiling approaches differentiate heterotrophic and mixotrophic culture conditions in a microalgal food supplement 'Euglena'. AB - BACKGROUND: Microalgae have been recognized as a good food source of natural biologically active ingredients. Among them, the green microalga Euglena is a very promising food and nutritional supplements, providing high value-added poly unsaturated fatty acids, paramylon and proteins. Different culture conditions could affect the chemical composition and food quality of microalgal cells. However, little information is available for distinguishing the different cellular changes especially the active ingredients including poly-saturated fatty acids and other metabolites under different culture conditions, such as light and dark. RESULTS: In this study, together with fatty acid profiling, we applied a gas chromatography-mass spectrometry (GC-MS)-based metabolomics to differentiate hetrotrophic and mixotrophic culture conditions. CONCLUSIONS: This study suggests metabolomics can shed light on understanding metabolomic changes under different culture conditions and provides a theoretical basis for industrial applications of microalgae, as food with better high-quality active ingredients. PMID- 27255276 TI - Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study. PMID- 27255275 TI - Trade and investment liberalization, food systems change and highly processed food consumption: a natural experiment contrasting the soft-drink markets of Peru and Bolivia. AB - BACKGROUND: Free trade agreements (FTAs) can affect food environments and non communicable disease risks through altering the availability of highly-processed foods. Few studies have quantified such effects. Using a natural experiment this paper quantifies changes in Peru's soft-drink market before/after entry into the US-Peru FTA, compared with Bolivia, a county with no such agreement. METHODS: Difference-in-difference models were used to test for between country differences in the rate of per capita foreign direct investment (FDI) inflows, soft-drink imports, the volumes of various soft-drinks sold, and the volumes of sugar from soft-drinks before/after FTA ratification (2006) and enforcement (2009). RESULTS: In Peru average per capita FDI-inflows rose from US$103.11 in the pre ratification period to US$269.79 post-ratification, with little change in Bolivia. This corresponded with a 122 % increase in Peruvian soft-drink production. There was a significant between-country difference in FDI-inflows pre /post-ratification (DID:1.07, 95 % CI:0.19-1.96; p = 0.01). Despite little difference in total per capita soft-drink sales volumes there was a significant between-country difference in per capita sugar from soft-drinks pre-/post enforcement (DID:-0.99, 95 % CI: -1.91-0.06; p = 0.03) with stagnated growth in Peru and continued growth in Bolivia. This resulted from stagnated sugar sweetened carbonates growth and increased bottled water, juice and sports & energy drinks growth in Peru, with continued carbonates growth in Bolivia. There was a significant between-country difference in per capita carbonates (DID: 1.44, 95 % CI: -2.52-0.36, p = 0.01) and bottled water (DID:0.63; 95 % CI: -0.01 1.26; p = 0.04) sales volumes. CONCLUSIONS: The FTA may have resulted in increased FDI-inflows and soft-drink production and also contributed to the diversification of soft drinks produced and sold in Peru with some positive (stagnated carbonates and increased bottled water) and some negative (increased juice and sports & energy drinks) implications for nutrition. These changes were not evident in Bolivia. These results should be interpreted cautiously given the study design limitations. PMID- 27255278 TI - Erratum to: Towards exergaming commons: composing the exergame ontology for publishing open game data. PMID- 27255277 TI - Sorting it out: bedding particle size and nesting material processing method affect nest complexity. AB - As part of routine husbandry, an increasing number of laboratory mice receive nesting material in addition to standard bedding material in their cages. Nesting material improves health outcomes and physiological performance in mice that receive it. Providing usable nesting material uniformly and efficiently to various strains of mice remains a challenge. The aim of this study was to determine how bedding particle size, method of nesting material delivery, and processing of the nesting material before delivery affected nest building in mice of strong (BALB/cAnNCrl) and weak (C3H/HeNCrl) gathering abilities. Our data suggest that processing nesting material through a grinder in conjunction with bedding material, although convenient for provision of bedding with nesting material 'built-in', negatively affects the integrity of the nesting material and subsequent nest-building outcomes. We also found that C3H mice, previously thought to be poor nest builders, built similarly scored nests to those of BALB/c mice when provided with unprocessed nesting material. This was true even when nesting material was mixed into the bedding substrate. We also observed that when nesting material was mixed into the bedding substrate, mice of both strains would sort their bedding by particle size more often than if it were not mixed in. Our findings support the utility of the practice of distributing nesting material mixed in with bedding substrate, but not that of processing the nesting material with the bedding in order to mix them. PMID- 27255279 TI - Tobacco TTG2 regulates vegetative growth and seed production via the predominant role of ARF8 in cooperation with ARF17 and ARF19. AB - BACKGROUND: Plant TRANSPARENT TESTA GLABRA (TTG) proteins regulate various developmental activities via the auxin signaling pathway. Recently, we elucidated the developmental role of tobacco (Nicotiana tabacum L.) NtTTG2 in association with 12 genes that putatively encode AUXIN RESPONSIVE FACTOR (ARF) proteins, including NtARF8, NtARF17, and NtARF19. Here we show that NtTTG2 regulates tobacco growth and development by involving the NtARF8, NtARF17, and NtARF19 genes, with the NtARF8 gene playing a predominant contribution. RESULTS: Independent silencing of the NtARF8 gene more strongly repressed tobacco growth than silencing the NtARF17 or NtARF19 gene and more effectively eradicated the growth enhancement effect of NtTTG2 overexpression. In contrast, plant growth was not affected by silencing additional nine NtTTG2-regulated NtARF genes. In double and triple gene silencing combinations, silencing the NtARF8 gene was more effective than silencing the NtARF17 or NtARF19 gene to repress growth as well as nullify growth enhancement. Therefore, the NtARF8 predominantly cooperated with the NtARF17 and NtAFR19 of the NtTTG2 functional pathway. NtARF8 also contributed to NtTTG2-regulated seed production as concurrent NtTTG2 and NtARF8 overexpression played a synergistic role in seed production quantity, whereas concurrent silencing of both genes caused more severe seed abortion than single gene silencing. In plant cells, the NtTTG2 protein facilitated the nuclear import of NtARF8 as well as increased its function as a transcription activator. CONCLUSIONS: NtARF8 is an integral component of the NtTTG2 functional pathway, which regulates tobacco growth and development. PMID- 27255280 TI - Pilot study evaluating a brief mindfulness intervention for those with chronic pain: study protocol for a randomized controlled trial. AB - BACKGROUND: The burden of chronic pain is a major challenge, impacting the quality of life of patients. Intensive programmes of mindfulness-based therapy can help patients to cope with chronic pain but can be time consuming and require a trained specialist to implement. The self-management model of care is now integral to the care of patients with chronic pain; home-based interventions can be very acceptable, making a compelling argument for investigating brief, self management interventions. The aim of this study is two-fold: to assess the immediate effects of a brief self-help mindfulness intervention for coping with chronic pain and to assess the feasibility of conducting a definitive randomized controlled trial to determine the effectiveness of such an intervention. METHODS/DESIGN: A randomized controlled pilot study will be conducted to evaluate a brief mindfulness intervention for those with chronic pain. Ninety chronic pain patients who attend hospital outpatient clinics will be recruited and allocated randomly to either the control or treatment group on a 1:1 basis using the computer-generated list of random numbers. The treatment group receives mindfulness audios and the control group receives audios of readings from a non fiction book, all of which are 15 minutes in length. Immediate effects of the intervention are assessed with brief psychological measures immediately before and after audio use. Mindfulness, mood, health-related quality of life, pain catastrophizing and experience of the intervention are assessed with standardized measures, brief ratings and brief telephone follow-ups, at baseline and after one week and one month. Feasibility is assessed by estimation of effect sizes for outcomes, patient adherence and experience, and appraisal of resource allocation in provision of the intervention. DISCUSSION: This trial will assess whether a brief mindfulness-based intervention is effective for immediately reducing perceived distress and pain with the side effect of increasing relaxation in chronic pain patients and will determine the feasibility of conducting a definitive randomized controlled trial. Patient recruitment began in January 2015 and is due to be completed in June 2016. TRIAL REGISTRATION: ISRCTN61538090 Registered 20 April 2015. PMID- 27255281 TI - Obesity Prevention and Weight Maintenance After Loss. AB - Obesity is one of the most prevalent medical diseases in pets. Outcomes are often disappointing; many animals either fail to reach target weight or regain weight. This article discusses managing obesity, focusing on prevention. It gives guidance on establishing monitoring programs that use regular body weight and condition assessments to identify animals at risk of inappropriate weight gain, enabling early intervention. Weight management in obese animals is a lifelong process. Regular weight and body condition monitoring are key to identifying animals that rebound early, while continuing to feed a therapeutic weight loss diet can help prevent it from happening. PMID- 27255282 TI - N-methyl-d-aspartate (NMDA) receptor antibodies encephalitis mimicking an autistic regression. AB - Expressive dysphasia and mutism are common clinical features in children and adults with N-methyl-d-aspartate receptor antibodies (NMDAR-Ab) encephalitis, and are likely to result from NMDAR hypofunction. A prodromal loss of social and communication skills can typify that of an autistic regression, particularly when presenting under the age of 3 years. Here we describe two toddlers who presented with developmental regression, particularly of their social communication skills, mimicking an autistic regression, who were found to have NMDAR-Ab in the serum and cerebrospinal fluid. Although both patients had some other neurological features, they were subtle, which resulted in delayed diagnosis of NMDAR-Ab encephalitis. Importantly, immunotherapy was beneficial in both patients, with significant improvement of their language skills and behaviour. PMID- 27255283 TI - Gallstone Disease and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Observational Studies. AB - OBJECTIVES: Gallstone disease shares certain risk factors with cardiovascular disease, particularly metabolic risk factors. Patients with gallstone disease may be at increased risk of cardiovascular disease. Several recent studies exploring the effect of gallstone disease on cardiovascular disease outcomes demonstrated inconsistent results. DESIGN: We conducted a systematic review and meta-analysis of cohort, case-control, and cross-sectional studies that compared the risk of developing cardiovascular disease events in patients with gallstone disease versus non-gallstone disease controls. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate the pooled hazard ratio, odd ratio, and 95% confidence interval. RESULTS: Data were extracted from six studies involving 176,734 cases and 803,714 controls. The pooled hazard ratio of cardiovascular events in patients with gallstone disease was 1.28 (95% confidence interval: 1.23-1.33, I2 = 42%). The pooled odd ratio of cardiovascular events in patients with gallstone disease was 1.82 (95% confidence interval: 1.47-2.24, I2 = 68%). CONCLUSIONS: Our study demonstrated a statistically significant increase in the risk of cardiovascular disease among patients with gallstone disease. PMID- 27255284 TI - Jean Forbes Trainer. PMID- 27255287 TI - Z-Score Reference Ranges for Angular M-Mode Displacement at 22-40 Weeks' Gestation. AB - OBJECTIVES: To construct Z-score reference ranges for fetal mitral and tricuspid annular plane systolic excursions (MAPSE and TAPSE), using angular M-mode (AM) and conventional M-mode (CM). METHODS: A prospective cross-sectional investigation was conducted on 261 normal singleton fetuses from 22 to 40 weeks' gestation. TAPSE and MAPSE were measured by AM and CM. Reference ranges of TAPSE and MAPSE derived from AM and CM were determined against gestational age (GA) and heart area (HA), using regression analyses of the mean and standard deviation. RESULTS: TAPSE and MAPSE showed positive correlations with GA and HA. A cubic regression was the best-fitted model for the mean of MAPSE and TAPSE based on HA, while a linear regression model was established for the mean based on GA. Z scores and 95% reference intervals for predicting MAPSE and TAPSE were established. Strong correlations were found between AM and CM, whereas CM underestimated AM (mean error: MAPSE 0.25 +/- 0.18 mm; TAPSE 0.35 +/- 0.2 mm). CONCLUSION: Normal data and the Z-scores of fetal MAPSE and TAPSE were provided against GA and HA, which can be useful for quantitative assessment of fetal cardiac dysfunction, particularly in cases of intrauterine growth restriction. PMID- 27255286 TI - The Road to Reproducibility in Animal Research. AB - Reproducibility of research findings is the hallmark of scientific advance. However, the recently noted lack of reproducibility and transparency of published research using animal models of human biology and disease has alarmed funders, scientists, and the public. Improved reporting of methodology and better use of statistical tools are needed to enhance the quality and utility of published research. Reporting guidelines like Animal Research: Reporting In Vivo Experiments (ARRIVE) have been devised to achieve these goals, but most biomedical research journals, including the JBMR, have not been able to obtain high compliance. Cooperative efforts among authors, reviewers and editors empowered by increased awareness of their responsibilities, and enabled by user friendly guidelines-are needed to solve this problem. (c) 2016 American Society for Bone and Mineral Research. PMID- 27255285 TI - Integrated omics approaches provide strategies for rapid erythromycin yield increase in Saccharopolyspora erythraea. AB - BACKGROUND: Omics approaches have significantly increased our understanding of biological systems. However, they have had limited success in explaining the dramatically increased productivity of commercially important natural products by industrial high-producing strains, such as the erythromycin-producing actinomycete Saccharopolyspora erythraea. Further yield increase is of great importance but requires a better understanding of the underlying physiological processes. RESULTS: To reveal the mechanisms related to erythromycin yield increase, we have undertaken an integrated study of the genomic, transcriptomic, and proteomic differences between the wild type strain NRRL2338 (WT) and the industrial high-producing strain ABE1441 (HP) of S. erythraea at multiple time points of a simulated industrial bioprocess. 165 observed mutations lead to differences in gene expression profiles and protein abundance between the two strains, which were most prominent in the initial stages of erythromycin production. Enzymes involved in erythromycin biosynthesis, metabolism of branched chain amino acids and proteolysis were most strongly upregulated in the HP strain. Interestingly, genes related to TCA cycle and DNA-repair were downregulated. Additionally, comprehensive data analysis uncovered significant correlations in expression profiles of the erythromycin-biosynthetic genes, other biosynthetic gene clusters and previously unidentified putative regulatory genes. Based on this information, we demonstrated that overexpression of several genes involved in amino acid metabolism can contribute to increased yield of erythromycin, confirming the validity of our systems biology approach. CONCLUSIONS: Our comprehensive omics approach, carried out in industrially relevant conditions, enabled the identification of key pathways affecting erythromycin yield and suggests strategies for rapid increase in the production of secondary metabolites in industrial environment. PMID- 27255288 TI - The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015. AB - This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths. PMID- 27255290 TI - Synthesis, structure elucidation, DNA-PK, PI3K, anti-platelet and anti-bacteria activity of linear 5, 6, and 10-substituted-2-morpholino-chromen-oxazine-dione and angular 3, 4, 6-substituted-8-morpholino-chromen-oxazine-2,10-dione. AB - Coumarin, a naturally occurring or synthesised phytochemical, displays a wide range of biological activities. However, chromen-2-ones fused with 1,3 benzoxazine rings is not well documented and there is a gap in the literature which required engaging. The substituted-2-thioxo-chromen-oxazine linear compounds 14a-i and angular compounds 16a-e were synthesised from the reaction of hydroxy-substituted-chromene-carboxylic 10-13 with freshly prepared Ph3P(SCN)2. 2 Morpholino-substituted-chromen-oxazine-4,8-dione and 8-morpholino-substituted chromen-oxazine-2,10-dione 15a-f and 17 were synthesised from the reaction of the corresponding oxazines 14 and 16 with morpholine. PI3K activity was observed for the hydroxy-substituted-chromene-carboxylic acid of which compound 13b showed moderate PI3Kgamma (IC50 = 5.56 MUM) and PI3Kalpha (IC50 = 14.7 MUM) activity. Additionally, 8-morpholino-chromen-oxazine-2,10-dione 17a showed isoform selective PI3Kdelta activity with IC50 = 5.08 MUM with non-DNA-PK >= 100 MUM. Consequently compound 17a can be considered as a selective PI3Kdelta inhibitor with non-DNA-PK at compound concentrations >=100 MUM. PMID- 27255291 TI - Right Atrial Dilatation, Determined by Echocardiography, and Correlation with Right Atrial Pressure, Determined with Cardiac Catheterization, in Children with Pulmonary Hypertension. PMID- 27255289 TI - Phase I study of orally administered S-1 in combination with epirubicin and oxaliplatin in patients with advanced solid tumors and chemotherapy-naive advanced or metastatic esophagogastric cancer. AB - BACKGROUND: This phase I study investigated the safety and the maximum tolerated dose (MTD) of the oral fluoropyrimidine S-1 when combined with epirubicin and oxaliplatin (EOS). METHODS: Patients aged >=18 years with advanced or metastatic solid tumors were enrolled in a 3 + 3 design with S-1 dose escalation (two planned cohorts) performed according to the occurrence of dose-limiting toxicity (DLT). On day 1 of each 21-day cycle, patients received epirubicin 50 mg/m2 followed by oxaliplatin 130 mg/m2 (maximum 8 cycles) and then S-1 [20 mg/m2 (cohort 1) or 25 mg/m2 (cohort 2), twice daily]: first dose, evening of day 1; subsequent administration on days 2-14, twice daily; last dose, morning of day 15 (unlimited number of S-1 cycles). After protocol amendment, enrollment in a third cohort was restricted to patients with chemotherapy-naive advanced or metastatic esophagogastric cancer. RESULTS: DLT was reported for two of the five patients in cohort 2, defining 20 mg/m2 twice daily as the MTD of S-1 combined with epirubicin and oxaliplatin in heavily pretreated patients. Thirteen patients with chemotherapy-naive advanced or metastatic esophagogastric cancer were subsequently enrolled and treated at an S-1 dose level of 25 mg/m2 twice daily; no DLTs were reported; median overall survival was 13.1 months. Of the 11 evaluable patients, three (27 %) had partial responses and seven (64 %) had stable disease. The safety profile was in line with expectations. CONCLUSIONS: The promising activity of EOS (S-1 dose level, 25 mg/m2 twice daily) and acceptable safety profile support further clinical development of this combination for the first-line treatment of patients with advanced or metastatic esophagogastric cancer. PMID- 27255292 TI - Decline of Systolic and Diastolic 2D Strain Rate During Follow-Up of HLHS Patients After Fontan Palliation. AB - Accurate assessment of ventricular function is particularly important in children with hypoplastic left heart syndrome (HLHS) after completion of the total cavopulmonary connection (TCPC). For this purpose, two-dimensional speckle tracking (2DST) is a promising technique as it does not depend on the angle of insonation or the geometry of the ventricle. The objective of this study was to assess changes in systolic and diastolic right ventricular (RV) function within a 5-year follow-up period of HLHS patients after TCPC using conventional and 2DST echocardiography. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), E/A, E/e' and 2DST parameters [global longitudinal peak systolic strain (GS) and strain rate (GSRs), global strain rate in early (GSRe) and late (GSRa) diastole] of 40 HLHS patients were compared at 1.6 and at 5.1 years after TCPC. RVFAC, E/A, E/e' and GS did not change, whereas TAPSE (13.7 +/- 3.2 vs. 10.5 +/- 2.4 mm/m(2), p < 0.001), GSRs (-1.56 +/- 0.28 vs. -1.35 +/- 0.31 1/s, p < 0.001), GSRe (2.22 +/- 0.49 vs. 1.96 +/- 0.44 1/s, p = 0.004) and GSRa (1.19 +/- 0.39 vs. 0.92 +/- 0.39 1/s, p < 0.001) decreased significantly. Systolic and diastolic RV function parameters of HLHS patients decreased from 1.6 to 5.1 years after TCPC in our patients. Changes in global strain rate parameters may be signaling early RV dysfunction that is not detectable by traditional echocardiography. Further study is needed to verify this and to determine whether these changes are clinically relevant. PMID- 27255293 TI - Intrapericardial left-sided ectopic thyroid mass supplied by the left circumflex artery. AB - Intrapericardial left-sided ectopic thyroid tissue is a rare entity. We report a 47-year old female patient with an intrapericardial mass mounting the left atrial wall. Two prominent vessels, both originating from the left circumflex artery (LCX), supplied the tumour. Owing to the compression of the left atrium and the left upper pulmonary vein, the patient was highly symptomatic with exertional dyspnoea and ventricular extrasystoles. Histopathological examination showed regressive thyroid adenoma with no signs of malignancy. Complete resection was feasible. The evaluation of thyroid hormone levels was not indicative for diagnosis. Postoperative hormone substitution appeared to be unnecessary. PMID- 27255294 TI - Benefits and medium-term outcome of the Sorin Pericarbon Freedom stentless aortic prosthesis in cases of acute bacterial endocarditis. AB - OBJECTIVES: The aim of this study is to evaluate the ease of use and the advantages of Sorin Pericarbon Freedom (SPF) stentless valve in cases of acute bacterial endocarditis and to check the intermediate-term results after the implant of SPF with respect to resistance to infection, valve deterioration and durability. METHODS: Between June 2003 and February 2015, 26 patients with active aortic valve bacterial endocarditis underwent aortic valve replacement with SPF pericardial stentless aortic prosthesis. The mean age was 57 +/- 18 years; 73% of the patients were in preoperative NYHA class III and VI. Mean Logistic EuroSCORE was 14.2 +/- 12.7. Endocarditis occurred in 18 patients with native valves, and in 9 patients with prosthetic valves (4 mechanical aortic valve prostheses; 5 aortic bioprostheses). Aortic root abscesses were observed in 16 cases (61.5%). Surgery was emergent in 3 cases (11.5%). Redo surgery was performed in 9 cases (35%). Cumulative follow-up was 126.8 patient-years (mean 4.9 +/- 3.3 years). RESULTS: Operative hospital mortality was 0% for all patients. Residual mean prosthetic gradient at discharge was 9.4 +/- 3.6 mmHg. Neither residual aortic incompetence nor residual abscess cavity was observed at discharge. Mean ejection fraction at discharge was 54 +/- 8% (Min; Max: 35%; 65%). A total of 4 patients died at follow-up, all for non-cardiac causes. One patient was lost to follow-up. Two patients (8%) underwent non-valve-related reoperation with 0% mortality. Residual mean gradient at follow-up was 7.2 +/- 2.1 mmHg. Three patients (17%) presented with mild/moderate aortic incompetence and 89% of patients were in NYHA Class I-II at follow-up. At 9 years, actuarial freedom from valve-related reoperation and from structural valve deterioration was 100%. CONCLUSIONS: The SPF aortic prosthesis is a true pericardial stentless prosthesis suitable for the treatment of acute bacterial endocarditis. Intermediate-time results in terms of freedom from reoperation, structural valve deterioration and resistance to infections are satisfactory. Haemodynamic performances are excellent since a complete exclusion of aortic root abscesses is achieved without any reduction of the aortic annular diameter, usually due to marsupialization or patch closure of the infected cavities. PMID- 27255296 TI - Evaluation of apoptotic cell death on liver and kidney tissues following administration of levetiracetam during prenatal period. AB - OBJECTIVE: Levetiracetam is a new generation antiepileptic drug used in treatment of patients with epilepsy and has adverse effects on different tissues. We aimed to evaluate the apoptotic effects of levetiracetam exposure during pregnancy on liver and kidney tissues of rat pups. METHODS: We analyzed the newborn rat pups exposed to levetiracetam during prenatal period. Fifteen pregnant female rats were divided into three groups. The group 1 and 2 rats were treated with different doses of levetiracetam (25 mg/kg/d and 50 mg/kg/d, respectively) from gestational days 1-22 during pregnancy. Group 3 (control group) was treated with the same volume of saline. Apoptosis was evaluated by the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) method. Liver and kidney tissues from rat pups were used for investigation. RESULTS: The percent of TUNEL positive apoptotic cells in group 1 were 22 and 17.5 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 2 were 20.9 and 20.9 for kidney and liver, respectively. The percent of TUNEL positive apoptotic cells in group 3 were 18.4 and 17.1, respectively, for kidney and liver. The apoptotic index was the same in kidney and liver tissues of all groups. CONCLUSION: Our results demonstrate that the prenatal exposure of levetiracetam has no apoptotic effects on liver and kidney of rat pups and, it has biosafety in pregnancy in terms of apoptosis. The first study evaluating the apoptotic effects on liver and kidney tissues following administration of levetiracetam during prenatal period. PMID- 27255295 TI - Association between SLC2A9 (GLUT9) gene polymorphisms and gout susceptibility: an updated meta-analysis. AB - The relationship between the SLC2A9 (solute carrier family 2, member 9) gene polymorphisms and gout was still inconsistent among the individual genetic association studies. Therefore, this present research was aimed to systematically evaluate the association between SLC2A9 gene polymorphisms and gout susceptibility. Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the associations. The heterogeneity between each of the studies was calculated by using the Q statistic methods, and Begg's funnel plot and Egger's tests were performed to evaluate publication bias. A total of 13 studies investigated four single nucleotide polymorphisms (SNPs) in SLC2A9 were included. In this study, we found that the allele C of rs3733591 was higher in patients than in controls in both all-pooled population [C vs. T: OR (95 % CI) = 1.432 (1.213-1.691)] and Asians-pooled population [C vs. T: OR (95 % CI) = 1.583 (1.365-1.835)]. The allele frequency C of s6449213 was lower in the gout patients than in controls in both all-pooled population and Caucasians-pooled population. Additionally, the allele frequency T of rs16890979 and the allele frequency C of rs1014290 were lower in gout patients than in controls. This study demonstrated that the genetic susceptibility for gout is associated with the SLC2A9 gene polymorphisms. Four of them except for the rs3733591 are protective SNPs in Caucasians, and rs16890979 and rs1014290 are protective SNPs in both Caucasians and Asians, while rs3733591 may be susceptibility SNP in Asians. PMID- 27255297 TI - Proposal to modify the Note to Rule 61 of the International Code of Nomenclature of Prokaryotes. AB - In view of the current difficulty to make minor typographical or orthographic corrections to incorrectly formed names of taxa, we propose a change in the text of the Note to Rule 61 of the International Code of Nomenclature of Prokaryotes, to be applied retroactively from August 2009. The proposed change will enable the List Editors of the International Journal of Systematic and Evolutionary Microbiology and others to correct minor errors without having to refer each case to the Judicial Commission of the International Committee for Systematics of Prokaryotes. PMID- 27255298 TI - [Food-induced anaphylaxis - data from the anaphylaxis registry]. AB - Anaphylactic reactions due to food occur in the context of food allergy and, together with venom and drugs, are the most frequent elicitors of severe allergic reactions. In small children the most frequent elicitors of severe allergic reactions according to data from the anaphylaxis registry are hen's egg and milk, whereas in school children peanut and hazelnut are frequent elicitors of allergic reactions. Other frequent elicitors of anaphylactic reactions in childhood are wheat and soy. In adults the most frequent elicitors of severe allergic reactions due to food, based on data from the anaphylaxis registry, are wheat, soy, celery, shellfish and hazelnut. Rare elicitors of food-induced anaphylaxis in German speaking countries are mustard and cabbage. However, the panel of rare elicitors of food-induced anaphylaxis show regional differences. As of March 2015, 17 cases of fatal anaphylaxis were registered and among these seven were food-induced. Co factors can either trigger the elicitation of a severe allergic reaction or affect its severity. Among such co-factors are physical activity, the intake of certain drugs, and psychological stress. The data on the role of cofactors is sparse. The management of food-induced anaphylaxis includes acute management according to current guidelines, but also long-term management, which should include educational measures regarding treatment but also information about the food allergen in daily life. PMID- 27255299 TI - [Dietary management of food allergies]. AB - A therapeutic diet is only indicated if the diagnosis of food allergy is certain. In the case of an unproven suspicion everything should be done to confirm or disprove the diagnosis by diagnostic measures (patient history, diet history, food and symptom protocol etc.). In the case of proven food allergy there are different aims of nutritional therapy. Most importantly the patient should learn how to identify his eliciting agent in pre-packed and non-prepacked food and how to avoid it. The elimination diet should take into account the individual condition of the patient. In particular, if basic foods have to be eliminated from the diet, safe alternatives have to be determined to maintain a nutritionally balanced diet and to maintain a high quality of life. To ensure the nutritional adequacy of the diet, micro- and macronutrient intake should be analysed and improved, if necessary. For pollen-associated food allergy and certain chronic conditions it might be necessary to be aware of possible triggering factors as well as potential cross-reactions. Moreover, individual tolerance should be maintained during elimination diets and not jeopardized by voluntary and unnecessary self-denial of certain foods.An effective individual management of food allergies by the patient is considerably dependent on the quality of the nutritional education and therapy. PMID- 27255300 TI - Evaluation of the impact of carotid artery bifurcation angle on hemodynamics by use of computational fluid dynamics: a simulation and volunteer study. AB - In this study, we evaluated the hemodynamics of carotid artery bifurcation with various geometries using simulated and volunteer models based on magnetic resonance imaging (MRI). Computational fluid dynamics (CFD) was analyzed by use of OpenFOAM. The velocity distribution, streamline, and wall shear stress (WSS) were evaluated in a simulated model with known bifurcation angles (30 degrees , 40 degrees , 50 degrees , 60 degrees , derived from patients' data) and in three dimensional (3D) healthy volunteer models. Separated flow was observed at the outer side of the bifurcation, and large bifurcation models represented upstream transfer of the point. Local WSS values at the outer bifurcation [both simulated (<30 Pa) and volunteer (<50 Pa) models] were lower than those in the inner region (>100 Pa). The bifurcation angle had a significant negative correlation with the WSS value (p<0.05). The results of this study show that the carotid artery bifurcation angle is related to the WSS value. This suggests that hemodynamic stress can be estimated based on the carotid artery geometry. The construction of a clinical database for estimation of developing atherosclerosis is warranted. PMID- 27255301 TI - Using LC-MS Based Methods for Testing the Digestibility of a Nonpurified Transgenic Membrane Protein in Simulated Gastric Fluid. AB - The digestibility of a nonpurified transgenic membrane protein was determined in pepsin, as part of the food safety evaluation of its resistance to digestion and allergenic potential. Delta-6-desaturase from Saprolegnia diclina, a transmembrane protein expressed in safflower for the production of gamma linolenic acid in the seed, could not be obtained in a pure, native form as normally required for this assay. As a novel approach, the endoplasmic reticulum isolated from immature seeds was digested in simulated gastric fluid (SGF) and the degradation of delta-6-desaturase was selectively followed by SDS-PAGE and targeted LC-MS/MS quantification using stable isotope-labeled peptides as internal standards. The digestion of delta-6-desaturase by SGF was shown to be both rapid and complete. Less than 10% of the initial amount of D6D remained intact after 30 s, and no fragments large enough (>3 kDa) to elicit a type I allergenic response remained after 60 min. PMID- 27255302 TI - Long-term outcomes in radically treated synchronous vs. metachronous oligometastatic non-small-cell lung cancer. AB - BACKGROUND: Radical treatment for oligometastatic non-small-cell lung cancer (NSCLC) has a curative potential for selected patients. The present retrospective study was designed to examine the relevance of synchronous vs. metachronous manifestations as a potential prognostic factor when ablative treatments are performed in oligometastatic disease. METHODS: Seventy-five patients with radically treated oligometastatic NSCLC were identified, of whom 39 presented with synchronous and 36 with metachronous metastatic manifestations. For patients with synchronous metastases, an additional therapy of the thoracic locoregional disease with a curative intent (either surgery or radiochemotherapy) was required. All patients with metachronous metastases had a documented remission of the primary tumor. Ablative treatment of the complete extent of oligometastatic disease consisted (as a minimum requirement) of either complete surgical resection or definitive ablative stereotactic radiotherapy. A comparative survival analysis of two groups of patients with oligometastatic NSCLC (synchronous vs. metachronous) and a complementary analysis of prognostic factors for the whole group of patients (by means of Cox regression analysis) was performed. Endpoints were median overall and progression-free survival (OS, PFS, respectively). RESULTS: Of the 75 patients, 57 presented with a solitary metastasis, in only 7 patients metastastatic lesions were present in >=2 organs and 66 patients had a Karnofsky performance score (KPS) of 80 % or 90 %. The median follow-up was 54.0 months (95 % CI 28-81), the median OS 21.8 months (16.1 27.6) and the median PFS 13.7 months (9.7-17.6). In univariable Cox regression analysis, no single clinical factor was significantly associated with OS. For PFS both 'metastatic involvement of >=2 organs vs. 1 organ' (hazard ratio (HR) 0.43, 0.23-0.83, p = 0.012) and a 'KPS of 90 % vs. 70-80 %' (HR 4.32, 1.73-10.89, p = 0.02) were significant prognostic factors as calculated by multivariable analysis. Comparing the cohorts with synchronous (n = 39) vs. metachronous oligometastases (n = 36), no differences in median OS and PFS were found. Both cohorts were well-balanced except for the KPS, which was significantly superior in patients with synchronous oligometastases. CONCLUSIONS: Radical treatment of oligometastatic NSCLC was associated with acceptable long-term survival rates in patients with good KPS and it was equally effective for synchronous and metachronous manifestations. PMID- 27255303 TI - Pulse Proteolysis and Precipitation for Target Identification. AB - In recent years, phenotypic screening has assumed a leading role in drug discovery efforts. However, development of new drugs from bioactive compounds obtained in screening campaigns requires identification of the cellular targets responsible for their biological activities. A new energetics-based method for target identification is presented: pulse proteolysis and precipitation for target identification (PePTID). In this method, proteins incubated with or without a ligand and submitted to a brief proteolytic pulse are directly analyzed and compared using a label-free semiquantitative mass spectrometry strategy, dispensing the SDS-PAGE readout and greatly improving the throughput. As a proof of-concept, we applied the PePTID method to identify ATP-binding proteins in Mycobacterium smegmatis, a model system for Mycobacterium tuberculosis, the etiological agent of tuberculosis. PMID- 27255304 TI - Impact of traffic-related air pollution on the expression of Platanus orientalis pollen allergens. AB - Air pollutants and their interaction with environmental allergens have been considered as an important reason for the recent increase in the prevalence of allergic diseases. The aim of this study was to investigate the traffic pollution effect, as a stressor, on Platanus orientalis pollen allergens messenger RNA (mRNA) and protein expression. P. orientalis pollen grains were collected along main streets of heavy traffic and from unpolluted sites in Mashhad city, in northeast Iran. The pollen samples were examined by scanning electron microscopy. To assess the abundance of pollen allergens (Pla or 1, Pla or 2, and Pla or 3) from polluted and unpolluted sites, immunoblotting was performed. Moreover, the sequences encoding P. orientalis allergens were amplified using real-time PCR. Scanning electron microscopy showed a number of particles of 150-550 nm on the surface of pollen from polluted sites. Also, protein and gene expression levels of Pla or 1 and Pla or 3 were considerably greater in pollen samples from highly polluted areas than in pollen from unpolluted areas (p < 0.05). In contrast, no statically significant difference in Pla or 2 protein and mRNA expression level was found between samples from the two areas. We found greater expression of allergens involved in plant defense mechanisms (Pla or 1 and Pla or 3) in polluted sites than in unpolluted ones. The high expression of these proteins can lead to an increase in the prevalence of allergic diseases. These findings suggest the necessity of supporting public policies aimed at controlling traffic pollution to improve air quality and prevent the subsequent clinical outcomes and new cases of asthma. PMID- 27255305 TI - Routine transfusion of platelet concentrates effectively reduces reoperation rate for bleeding and pericardial effusion after elective operations for ascending aortic aneurysm. AB - Patients with ascending aortic aneurysm undergoing complex surgical procedures are at increased risk of early postoperative excessive blood loss. The aim of this study was to analyze safety and efficacy of routine transfusions of platelet (PLT) concentrates in reduction of hemorrhagic postoperative complications. The study involved 396 consecutive patients (289 males and 107 females) with the mean age of 55.9 +/- 13.6 years who underwent elective operations for aortic aneurysms. They were divided retrospectively into two groups, without (group A; n = 123) or with the routine use of PLTs (group B; n = 273). PLTs were transfused intraoperatively just after completion of cardiopulmonary bypass. Twelve patients in group A (9.8%) and 10 (3.7%) in group B required re-thoracotomy due to hemorrhage (p = 0.027). Routine transfusions of PLT concentrates reduced postoperative incidence of excessive pericardial effusion from 24.1% in group A to 2.1% in group B (p = 0.002). In a consequence, significantly less units (p < 0.0001) of red blood concentrates and fresh frozen plasma were transfused in group B than in group A. The rates of other adverse events in the early postoperative period did not differ between groups. Patients with pericardial effusion required 6.3 +/- 2.7 additional days of hospitalization due to surgical re-intervention. Neither blood transfusion-related infections nor adverse reactions were noted. In conclusion, routine intraoperative transfusions of PLT concentrates in patients with ascending aortic aneurysms significantly reduced a need for re-intervention due to both early bleeding and late cardiac tamponade. PMID- 27255306 TI - Sexual Identity Mobility and Depressive Symptoms: A Longitudinal Analysis of Moderating Factors Among Sexual Minority Women. AB - Sexual minority identity (bisexual, lesbian) is a known risk factor for depression in women. This study examined a facet of minority stress prevalent among women-sexual identity mobility-as an identity-related contributor to higher levels of depressive symptoms. We used three waves of data from the Chicago Health and Life Experiences of Women study, a longitudinal study of sexual minority women (N = 306). Random effects OLS regression models were constructed to examine the effect of sexual identity changes on depressive symptoms. We found that 25.6 % of the sample reported a sexual identity change between Wave I and Wave II, and 24.9 % reported a sexual identity change between Waves II and III. Women who reported a change in sexual identity also reported more depressive symptoms subsequent to identity change. This effect was moderated by the number of years participants had reported their baseline identity and by whether the participant had initiated a romantic relationship with a male partner. PMID- 27255308 TI - Marsupials as models for understanding the role of chromosome rearrangements in evolution and disease. AB - Chromosome rearrangements have been implicated in diseases, such as cancer, and speciation, but it remains unclear whether rearrangements are causal or merely a consequence of these processes. Two marsupial families with very different rates of karyotype evolution provide excellent models in which to study the role of chromosome rearrangements in a disease and evolutionary context. The speciose family Dasyuridae displays remarkable karyotypic conservation, with all species examined to date possessing nearly identical karyotypes. Despite the seemingly high degree of chromosome stability within this family, they appear prone to developing tumours, including transmissible devil facial tumours. In contrast, chromosome rearrangements have been frequent in the evolution of the species-rich family Macropodidae, which displays a high level of karyotypic diversity. In particular, the genus Petrogale (rock-wallabies) displays an extraordinary level of chromosome rearrangement among species. For six parapatric Petrogale species, it appears that speciation has essentially been caught in the act, providing an opportunity to determine whether chromosomal rearrangements are a cause or consequence of speciation in this system. This review highlights the reasons that these two marsupial families are excellent models for testing hypotheses for hotspots of chromosome rearrangement and deciphering the role of chromosome rearrangements in disease and speciation. PMID- 27255309 TI - Diabetes treatment intensification and associated changes in HbA1c and body mass index: a cohort study. AB - BACKGROUND: To describe common type 2 diabetes treatment intensification regimens, patients' characteristics and changes in glycated hemoglobin (HbA1c) and body mass index (BMI). METHODS: We constructed a national retrospective cohort of veterans initially treated for diabetes with either metformin or sulfonylurea from 2001 through 2008, using Veterans Health Administration (VHA) and Medicare data. Patients were followed through September, 2011 to identify common diabetes treatment intensification regimens. We evaluated changes in HbA1c and BMI post-intensification for metformin-based regimens. RESULTS: We identified 323,857 veterans who initiated diabetes treatment. Of these, 55 % initiated metformin, 43 % sulfonylurea and 2 % other regimens. Fifty percent (N = 89,057) of metformin initiators remained on metformin monotherapy over a median follow-up 58 months (interquartile range [IQR] 35, 74). Among 80,725 patients who intensified metformin monotherapy, the four most common regimens were addition of sulfonylurea (79 %), thiazolidinedione [TZD] (6 %), or insulin (8 %), and switch to insulin monotherapy (2 %). Across these regimens, median HbA1c values declined from a range of 7.0-7.8 % (53-62 mmol/mol) at intensification to 6.6-7.0 % (49-53 mmol/mol) at 1 year, and remained stable up to 3 years afterwards. Median BMI ranged between 30.5 and 32 kg/m(2) at intensification and increased very modestly in those who intensified with oral regimens, but 1-2 kg/m(2) over 3 years among those who intensified with insulin-based regimens. CONCLUSIONS: By 1 year post intensification of metformin monotherapy, HbA1c declined in all four common intensification regimens, and remained close to 7 % in subsequent follow-up. BMI increased substantially for those on insulin-based regimens. PMID- 27255307 TI - A Review of the Status of Brain Structure Research in Transsexualism. AB - The present review focuses on the brain structure of male-to-female (MtF) and female-to-male (FtM) homosexual transsexuals before and after cross-sex hormone treatment as shown by in vivo neuroimaging techniques. Cortical thickness and diffusion tensor imaging studies suggest that the brain of MtFs presents complex mixtures of masculine, feminine, and demasculinized regions, while FtMs show feminine, masculine, and defeminized regions. Consequently, the specific brain phenotypes proposed for MtFs and FtMs differ from those of both heterosexual males and females. These phenotypes have theoretical implications for brain intersexuality, asymmetry, and body perception in transsexuals as well as for Blanchard's hypothesis on sexual orientation in homosexual MtFs. Falling within the aegis of the neurohormonal theory of sex differences, we hypothesize that cortical differences between homosexual MtFs and FtMs and male and female controls are due to differently timed cortical thinning in different regions for each group. Cross-sex hormone studies have reported marked effects of the treatment on MtF and FtM brains. Their results are used to discuss the early postmortem histological studies of the MtF brain. PMID- 27255310 TI - Effects of organic acids on the photosynthetic and antioxidant properties and accumulations of heavy metals of Melilotus officinalis grown in Cu tailing. AB - The effect of citric acid (CA), acetic acid (Ac), and ethylene diamine tetraacetic acid (EDTA) on the photosynthetic and antioxidant properties and the accumulation of some heavy metals (HMs) of Melilotus officinalis seedling growing in Cu mine tailings for 25 days were studied. Results showed that the formation of photosynthesizing cells of M. officinalis was inhibited by EDTA at 2 mmol/kg. Photosynthetic pigment contents under EDTA of 2 mmol/kg were reduced by 26, 40, and 19 %, respectively, compared to the control. The proline contents in aboveground and underground parts increased as the level of EDTA was enhanced. CA and Ac enhanced the activities of superoxide dismutase (SOD) and peroxidase (POD) in the aboveground parts and EDTA inhibited the activity of POD in the underground parts. The addition of CA promoted significantly the growth of M. officinalis, while the biomass decreased significantly under 2 mmol/kg EDTA. Cu contents in the aboveground parts treated with 0.5 and 2.0 mmol/kg EDTA reached 175.50 and 265.17 MUg/g dry weight, respectively. Ac and EDTA treatments promoted Cd to translocate from root to aboveground parts. The result indicated that M. officinalis was a tolerant species of Cu tailing and can be used to remediate Cu contaminated environment, and rationally utilization of organic acids, especially EDTA, in the phytoremediation can improve the growth and metals accumulation of M. officinalis. PMID- 27255311 TI - Toxicity of Cu (II) to the green alga Chlorella vulgaris: a perspective of photosynthesis and oxidant stress. AB - The toxic effects of Cu (II) on the freshwater green algae Chlorella vulgaris and its chloroplast were investigated by detecting the responses of photosynthesis and oxidant stress. The results showed that Cu (II) arrested the growth of C. vulgaris and presented in a concentration- and time-dependent trend and the SRichards 2 model fitted the inhibition curve best. The chlorophyll fluorescence parameters, including qP, Y (II), ETR, F v /F m , and F v /F 0, were stimulated at low concentration of Cu (II) but declined at high concentration, indicating the photosystem II (PSII) of C. vulgaris was destroyed by Cu (II). The chloroplasts were extracted, and the Hill reaction activity (HRA) of chloroplast was significantly decreased with the increasing Cu (II) concentration under both illuminating and dark condition, and faster decline speed was observed under dark condition. Activities of superoxide dismutase (SOD) and catalase (CAT) and malondialdehyde (MDA) content were also significantly decreased at high concentration Cu (II), companied with a large number of reactive oxygen species (ROS) production. All these results indicated a severe oxidative stress on algal cells occurred as well as the effect on photosynthesis, thus inhibiting the growth of algae, which providing sights to evaluate the phytotoxicity of Cu (II). PMID- 27255312 TI - Water reclamation during drinking water treatments using polyamide nanofiltration membranes on a pilot scale. AB - The aim of this study was to investigate the performances of polyamide nanofiltration membranes during water reclamation. The study was conducted using nanofiltration concentrates obtained from two different nanofiltration drinking water treatment plants placed in the northern part of Serbia (Kikinda and Zrenjanin). Used nanofiltration concentrates contained high concentrations of arsenic (45 and 451 MUg/L) and natural organic matter (43.1 and 224.40 mgKMnO4/L). Performances of polyamide nanofiltration membranes during water reclamation were investigated under various fluxes and transmembrane pressures in order to obtain drinking water from nanofiltration concentrates and, therefore, reduce the amount of produced concentrates and minimize the waste that has to be discharged in the environment. Applied polyamide nanofiltration membranes showed better removal efficiency during water reclamation when the concentrate with higher content of arsenic and natural organic matter was used while the obtained permeates were in accordance with European regulations. This study showed that total concentrate yield can be reduced to ~5 % of the optimum flux value, in both experiments. The obtained result for concentrate yield under the optimum flux presents considerable amount of reclaimed drinking water and valuable reduced quantity of produced wastewater. PMID- 27255313 TI - Effects of production conditions on yield and physicochemical properties of biochars produced from rice husk and oil palm empty fruit bunches. AB - Biochar is the bio-solid material produced by pyrolysis. The biochar properties are controlled by feedstock and pyrolysis variables. In this study, the impacts of these production variables on biochar yield and physicochemical properties including pH, cation exchange capacity (CEC), total organic carbon (TOC) content, surface area, and pore volume and size were investigated. Rice husk (RH) and oil palm empty fruit bunches (EFB) were used as biomass. The biochars were produced at temperature range of 300 to 700 degrees C, heating rate of 3 to 10 degrees C/min and retention time of 1 to 3 h. The pyrolysis conditions were optimized using response surface methodology (RSM) technique to maximize the values of the responses. Analysis of variance (ANOVA) of the results demonstrated that the data fitted well to the linear and quadratic equations. Temperature was found to be the most effective parameter on the responses followed by retention time and heating rate, sequentially. CEC, TOC, surface area, and pore characteristics were evaluated as biochar properties determining their sorption potential. The optimum conditions for the maximum values of the properties were temperatures of 700 and 493.44 degrees C and time of 3 and 1 h for RH and EFB biochars, respectively. Heating rate at 3 degrees C/min was found to be the best rate for both biochars. The structure of EFB biomass was more sensitive to heating than rice husk. The biomass type and the production variables were demonstrated as the direct effective factors on biochar yield and physicochemical properties. PMID- 27255314 TI - Cadmium (Cd) distribution and contamination in Chinese paddy soils on national scale. AB - Rice is a staple food by an increasing number of people in China. As more issues have arisen in China due to rice contaminated by cadmium (Cd), Cd contamination in arable soils has become a severe problem. In China, many studies have examined Cd contamination in arable soils on a national scale, but little studies have focused on the distribution of Cd in paddy fields. This study explored the spatial pattern of Cd in paddy soils in China, made a preliminary evaluation of the potential risk, and identified the most critically contaminated regions based on the domestic rough rice trade flow. The results showed that Cd concentrations in paddy soils in China ranged from 0.01 to 5.50 mg/kg, with a median value of 0.23 mg/kg. On average, the highest Cd concentrations were in Hunan (0.73 mg/kg), Guangxi (0.70 mg/kg), and Sichuan (0.46 mg/kg) provinces. Cd concentrations in paddy soils in central and western regions were higher than those in eastern regions, especially the southeastern coastal regions. Of the administrative regions, Cd standard exceedance rate was 33.2 %, and the heavy pollution rate was 8.6 %. Regarding to Cd of paddy soil, soil environmental quality was better in Northeast China Plain than in Yangtze River Basin and southeastern coastal region. Mining activities were the main anthropogenic pollution source of Cd in Chinese paddy soil. Based on rice trade, more of the Chinese population would be exposed to Cd through intake of rice produced in Hunan province. Certain regions that output rice, especially Hunan province, should be given priority in the management and control of Cd contamination in paddy soil. PMID- 27255315 TI - Degradation of Direct Red 81 mediated by Fenton reactions: multivariate optimization, effect of chloride and sulfate, and acute ecotoxicity assessment. AB - The role of different operational parameters related to Fenton reactions (pH, concentration of Fe2+ and H2O2, and reaction time) and of Cl- and SO 4- was investigated in the degradation of the azo dye Direct Red 81, expressed in terms of its decolorization. The factorial design and Pareto's charts showed that only Fe2+ concentration and pH influence the decolorization under the conditions evaluated. So, only these parameters were optimized using the response surface model. Under the best experimental conditions (initial pH 2.5, 11 mg L-1 Fe2+, 78 mg L-1 H2O2, and 20 min of reaction), 94 % of decolorization was achieved. However, even under the these conditions, but in the presence of Cl- and SO 4- , a striking loss of efficiency was observed as the concentration of these ions was increased, due the formation of chloride- and sulfate-iron complexes and less reactive inorganic radicals (Cl2*- and SO4*-). The results show that the presence of Cl- is more deleterious, since sulfate-iron complexes are more reactive towards H2O2, and the SO4*- turns out to favor the degradation. On the other hand, the negative effect of Cl- can be compensated by increasing the chloride concentration up to 300 mmol L-1. In addition, although a high degradation level has been obtained by monitoring the dye absorbance and by HPLC-UV, a low mineralization occurred, being generated degradation products of higher ecotoxicity to Vibrio fischeri, showing the need of subsequent studies to identify these compounds as well as the application of additional treatments aiming the complete mineralization of the dye. PMID- 27255317 TI - Trends and variations of pH and hardness in a typical semi-arid river in a monsoon climate region during 1985-2009. AB - The rapid growth of urbanization and industrialization, along with dramatic climate change, has strongly influenced hydrochemical characteristics in recent decades in China and thus could cause the variation of pH and general total hardness of a river. To explore such variations and their potential influencing factors in a river of the monsoon climate region, we analyzed a long-term monitoring dataset of pH, SO4 (2-), NOx, general total hardness (GH), Mg(2+), Ca(2+), and Cl(-) in surface water and groundwater in the Luan River basin from 1985 to 2009. The nonparametric Seasonal Kendall trend test was used to test the long-term trends of pH and GH. Relationship between the affecting factors, pH and GH were discussed. Results showed that pH showed a decreasing trend and that GH had an increasing trend in the long-term. Seasonal variation of pH and GH was mainly due to the typical monsoon climate. Results of correlation analysis showed that the unit area usage amounts of chemical fertilizer, NO3 (-), and SO4 (2-) were negatively correlated with pH in groundwater. In addition, mining activity affected GH spatial variation. Acid deposition, drought, and increasing the use of chemical fertilizers would contribute to the acidification trend, and mining activities would affect the spatial variation of GH. Variations of precipitation and runoff in semi-arid monsoon climate areas had significant influences on the pH and GH. Our findings implied that human activities played a critical role in river acidification in the semi-arid monsoon climate region of northern China. PMID- 27255318 TI - Molecular and phenotypic responses of Japanese medaka (Oryzias latipes) early life stages to environmental concentrations of cadmium in sediment. AB - Japanese medaka embryos were exposed to environmental concentrations of cadmium (Cd) to investigate adverse and adaptive responses in fish early life stages. Embryos were exposed during their whole development by static sediment-contact to environmental Cd concentrations (2 and 20 MUg/g dry weight). Cd bioaccumulation, developmental defects, biochemical and biomolecular (qRT-PCR) responses were analyzed in embryos and hatchlings. A dose-dependent increase of Cd bioaccumulation and developmental defects was observed at hatching. Cd had clear impacts on heartbeat and cardiac morphogenesis and also induced to spinal deformities. The profile and the level of gene transcription were differentially modulated according to the Cd concentration, the duration of exposure and/or the developmental stage of fish. Pro-apoptotic bax and DNA repair rad51 transcripts were significantly repressed in embryos exposed to the highest Cd concentration. Repression of these genes was correlated to the increase of heart rate in 6-day old embryos. NADH-dehydrogenase nd5 gene transcription was inhibited in larvae at the lowest concentration suggesting mitochondrial respiratory chain impairment, in association with Cd-induced teratogenicity. Finally, wnt1 gene was overexpressed indicating putative deregulation of Wnt signaling pathway, and suggested to be implied in the occurrence of some spinal and cardiac deformities. Results of this study permitted to propose some promising markers at the transcriptional and phenotypical level, responding to environmental concentrations of Cd. The present work also highlights the usefulness of the modified version of the medaka embryo-larval assay with sediment-contact exposure (MELAc) to investigate the toxicity and the modes of action of sediment-bound pollutants. PMID- 27255316 TI - Adsorptive amputation of hazardous azo dye Congo red from wastewater: a critical review. AB - Increasing amount of dyes in an ecosystem has propelled the search of various methods for dye removal. Amongst all the methods, adsorption occupies a prominent place in dye removal. Keeping this in mind, many adsorbents used for the removal of hazardous anionic azo dye Congo red (CR) from aqueous medium were reviewed by the authors. The main objectives behind this review article are to assemble the information on scattered adsorbents and enlighten the wide range of potentially effective adsorbents for CR removal. Thus, CR sorption by various adsorbents such as activated carbon, non-conventional low-cost materials, nanomaterials, composites and nanocomposites are surveyed and critically reviewed as well as their sorption capacities are also compared. This review also explores the grey areas of the adsorption performance of various adsorbents with reference to the effects of pH, contact time, initial dye concentration and adsorbent dosage. The equilibrium adsorption isotherm, kinetic and thermodynamic data of different adsorbents used for CR removal were also analysed. It is evident from a literature survey of more than 290 published papers that nanoparticle and nanocomposite adsorbents have demonstrated outstanding adsorption capabilities for CR. Graphical abstract ?. PMID- 27255319 TI - Solar-driven photocatalytic treatment of diclofenac using immobilized TiO2-based zeolite composites. AB - The study is aimed at evaluating the potential of immobilized TiO2-based zeolite composite for solar-driven photocatalytic water treatment. In that purpose, TiO2 iron-exchanged zeolite (FeZ) composite was prepared using commercial Aeroxide TiO2 P25 and iron-exchanged zeolite of ZSM5 type, FeZ. The activity of TiO2-FeZ, immobilized on glass support, was evaluated under solar irradiation for removal of diclofenac (DCF) in water. TiO2-FeZ immobilized in a form of thin film was characterized for its morphology, structure, and composition using scanning electron microscopy/energy-dispersive x-ray spectroscopy (SEM/EDX). Diffuse reflectance spectroscopy (DRS) was used to determine potential changes in band gaps of prepared TiO2-FeZ in comparison to pure TiO2. The influence of pH, concentration of hydrogen peroxide, FeZ wt% within the composite, and photocatalyst dosage on DCF removal and conversion efficiency by solar/TiO2 FeZ/H2O2 process was investigated. TiO2-FeZ demonstrated higher photocatalytic activity than pure TiO2 under solar irradiation in acidic conditions and presence of H2O2. PMID- 27255320 TI - Degradation of ethyl paraben by heat-activated persulfate oxidation: statistical evaluation of operating factors and transformation pathways. AB - A factorial design methodology was implemented to evaluate the importance of ethyl paraben (EP) concentration (500-1500 MUg/L), sodium persulfate concentration (400-500 mg/L), temperature (40-60 degrees C), reaction time (2-30 min), water matrix (pure water or secondary treated wastewater), and initial solution pH (3-9) on EP removal by heat-activated persulfate oxidation. All individual effects, except the solution pH, were statistically significant and so were the second-order interactions of ethyl paraben concentration with temperature or the reaction time. The influence of the water matrix was crucial, and the efficiency of the process was lower in secondary treated wastewater due to the presence of natural organic matter and inorganic salts that compete with ethyl paraben for the reactive oxygen species. Liquid chromatography time-of flight mass spectrometry (LC-TOF-MS) was employed to identify major transformation by-products (TBPs); 13 compounds were detected as TBPs of EP. Degradation occurred through (i) hydroxylation, (ii) dealkylation, and (iii) oligomerization reactions leading to TBPs with ether and biphenyl structures. Oligomerization reactions were found to be the dominant pathway during the first steps of the reaction. The toxicity of 500 MUg/L EP in secondary treated wastewater was tested against marine bacteria Vibrio fischeri; toxicity increased during the first minutes due to the production of several TBPs, but it consistently decreased thereafter. PMID- 27255322 TI - Evaluating levels and health risk of heavy metals in exposed workers from surgical instrument manufacturing industries of Sialkot, Pakistan. AB - The study aimed to monitor heavy metal (chromium, Cr; cadmium, Cd; nickel, Ni; copper, Cu; lead, Pb; iron, Fe; manganese, Mn; and zinc, Zn) footprints in biological matrices (urine, whole blood, saliva, and hair), as well as in indoor industrial dust samples, and their toxic effects on oxidative stress and health risks in exposed workers. Overall, blood, urine, and saliva samples exhibited significantly higher concentrations of toxic metals in exposed workers (Cr; blood 16.30 MUg/L, urine 58.15 MUg/L, saliva 5.28 MUg/L) than the control samples (Cr; blood 5.48 MUg/L, urine 4.47 MUg/L, saliva 2.46 MUg/L). Indoor industrial dust samples also reported to have elevated heavy metal concentrations, as an example, Cr quantified with concentration of 299 mg/kg of dust, i.e., more than twice the level of Cr in household dust (136 mg/kg). Superoxide dismutase (SOD) level presented significant positive correlation (p <= 0.01) with Cr, Zn, and Cd (Cr > Zn > Cd) which is an indication of heavy metal's associated raised oxidative stress in exposed workers. Elevated average daily intake (ADI) of heavy metals resulted in cumulative hazard quotient (HQ) range of 2.97-18.88 in workers of different surgical units; this is an alarming situation of health risk implications. Principal component analysis-multiple linear regression (PCA-MLR) based pie charts represent that polishing and cutting sections exhibited highest metal inputs to the biological and environmental matrices than other sources. Heavy metal concentrations in biological matrices and dust samples showed a significant positive correlation between Cr in dust, urine, and saliva samples. Current study will help to generate comprehensive base line data of heavy metal status in biomatrices and dust from scientifically ignored industrial sector. Our findings can play vital role for health departments and industrial environmental management system (EMS) authorities in policy making and implementation. PMID- 27255323 TI - Use of sugarcane filter cake and nitrogen, phosphorus and potassium fertilization in the process of bioremediation of soil contaminated with diesel. AB - This study evaluated the use of sugarcane filter cake and nitrogen, phosphorus and potassium (NPK) fertilization in the bioremediation of a soil contaminated with diesel fuel using a completely randomized design. Five treatments (uncontaminated soil, T1; soil contaminated with diesel, T2; soil contaminated with diesel and treated with 15 % (wt) filter cake, T3; soil contaminated with diesel and treated with NPK fertilizer, T4; and soil contaminated with diesel and treated with 15 % (wt) filter cake and NPK fertilizer, T5) and four evaluation periods (1, 60, 120, and 180 days after the beginning of the experiment) were used according to a 4 * 5 factorial design to analyze CO2 release. The variables total organic carbon (TOC) and total petroleum hydrocarbons (TPH) remaining in the soil were analyzed using a 5 * 2 factorial design, with the same treatments described above and two evaluation periods (1 and 180 days after the beginning of the experiment). In T3 and T5, CO2 release was significantly higher, compared with the other treatments. Significant TPH removal was observed on day 180, when percent removal values were 61.9, 70.1, 68.2, and 75.9 in treatments T2, T3, T4, and T5, respectively, compared with the initial value (T1). PMID- 27255321 TI - Heavy metal and trace elements in riparian vegetation and macrophytes associated with lacustrine systems in Northern Patagonia Andean Range. AB - Vegetation associated with lacustrine systems in Northern Patagonia was studied for heavy metal and trace element contents, regarding their elemental contribution to these aquatic ecosystems. The research focused on native species and exotic vascular plant Salix spp. potential for absorbing heavy metals and trace elements. The native species studied were riparian Amomyrtus luma, Austrocedrus chilensis, Chusquea culeou, Desfontainia fulgens, Escallonia rubra, Gaultheria mucronata, Lomatia hirsuta, Luma apiculata, Maytenus boaria, Myrceugenia exsucca, Nothofagus antarctica, Nothofagus dombeyi, Schinus patagonicus, and Weinmannia trichosperma, and macrophytes Hydrocotyle chamaemorus, Isoetes chubutiana, Galium sp., Myriophyllum quitense, Nitella sp. (algae), Potamogeton linguatus, Ranunculus sp., and Schoenoplectus californicus. Fresh leaves were analyzed as well as leaves decomposing within the aquatic bodies, collected from lakes Futalaufquen and Rivadavia (Los Alerces National Park), and lakes Moreno and Nahuel Huapi (Nahuel Huapi National Park). The elements studied were heavy metals Ag, As, Cd, Hg, and U, major elements Ca, K, and Fe, and trace elements Ba, Br, Co, Cr, Cs, Hf, Na, Rb, Se, Sr, and Zn. Geochemical tracers La and Sm were also determined to evaluate contamination of the biological tissues by geological particulate (sediment, soil, dust) and to implement concentration corrections. PMID- 27255324 TI - Adsorptive removal of naphthalene induced by structurally different Gemini surfactants in a soil-water system. AB - A new generation of surfactant, Gemini surfactants, have been synthesized and have attracted the attention of various industrial and academic research groups. This study focused on the use of symmetric and dissymmetric quaternary ammonium Gemini surfactants to immobilize naphthalene onto soil particles, and is used as an example of an innovative application to remove HOC in situ using the surfactant-enhanced sorption zone. The sorption capacity of modified soils by Gemini surfactant and natural soils was compared and the naphthalene sorption efficiency, in the absence and presence of Gemini surfactants with different alkyl chain lengths, was investigated in the soil-water system. The results have shown that the increased added Gemini surfactant formed admicelles at the interface of soil/water having superior capability to retard contaminant. Symmetric and dissymmetric Gemini surfactants have opposite effect on the aspect of removing of PAH attributing to their solubilization and sorption behavior in soil-water system. Compared with the natural soil, sorption of naphthalene by Gemini-modified soil is noticeably enhanced following the order of C12-2-16 < C12 2-12 < C12-2-8. However, the symmetric Gemini surfactant C12-2-12 is the optimized one for in situ barrier remediation, which is not only has relative high retention ability but also low dosage. PMID- 27255326 TI - Covalent versus Charge Transfer Modification of Graphene/Carbon-Nanotubes with Vitamin B1: Co/N/S-C Catalyst toward Excellent Oxygen Reduction. AB - High-performance nonprecious cathodic catalysts for oxygen reduction are highly demanded for low-temperature polymer electrolyte membrane fuel cells (PEMFCs). Here, we report a noble-meta- free, nitrogen and sulfur codoped graphene(G)/carbon-nanotube(CNT) material decorated with Co nanoparticles (NPs), which serve as catalytic sites for excellent oxygen reduction reaction (ORR) in basic and acidic media. Out of the cathodic catalysts synthesized by either covalent (cov) or charge transfer (CT) modification of graphen oxide (GO) with thiamine (Th: Vitamin B1), ThG/CNT/Co-cov shows more promising ORR properties than ThG/CNT/Co-CT. Catalyst ThG/CNT/Co-cov exhibits onset/halfwave potentials of 0.95/0.86 V in 0.1 M KOH and 0.92/0.83 V in 0.1 M HClO4, which are comparable to those of commercial catalyst Pt/C (0.95/0.86 V). As compared to Pt/C, our catalyst shows higher current densities of 6.72 mA cm(-2) in basic medium and 7.08 mA cm(-2) in acidic medium at 0.55 V (vs reversible hydrogen electrode (RHE)). It also exhibits better catalytic stability and methanol tolerance. High catalytic efficiency and stability of ThG/CNT/Co-cov show a promising prospect of materialization of PEMFCs for clean energy production. PMID- 27255325 TI - Suitability of passive sampling for the monitoring of pharmaceuticals in Finnish surface waters. AB - The occurrence of five pharmaceuticals, consisting of four anti-inflammatory and one antiepileptic drug, was studied by passive sampling and grab sampling in northern Lake Paijanne and River Vantaa. The passive sampling was performed by using Chemcatcher(r) sampler with a SDB-RPS Empore disk as a receiving phase. In Lake Paijanne, the sampling was conducted during summer 2013 at four locations near the discharge point of a wastewater treatment plant and in the years 2013 and 2015 at four locations along River Vantaa. The samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring mode. The concentrations of carbamazepine, diclofenac, ibuprofen, ketoprofen, and naproxen in Lake Paijanne determined by passive sampling ranged between 1.4-2.9 ng L(-1), 15-35 ng L(-1), 13-31 ng L(-1), 16-27 ng L(-1), and 3.3-32 ng L(-1), respectively. Similarly, the results in River Vantaa ranged between 1.2-40 ng L(-1), 15-65 ng L(-1), 13-33 ng L(-1), 16 31 ng L(-1), and 3.3-6.4 ng L(-1). The results suggest that the Chemcatcher passive samplers are suitable for detecting pharmaceuticals in lake and river waters. PMID- 27255327 TI - Protocol for a systematic review of the efficacy of epidermal grafting for wound healing. AB - BACKGROUND: Autologous skin grafting is an important modality for wound coverage; however, it can result in donor site morbidity. Epidermal grafting is an emerging option to overcome this challenge. Furthermore, it can be done in an outpatient setting with minimal or no pain. To date, the evidence on the efficacy of this technique for wound healing has yet to be outlined. We aim to synthesise the current evidence on epidermal grafting for wound healing to establish the efficacy of this technique. METHODS/DESIGN: We will conduct a comprehensive search in the MEDLINE, EMBASE, and CENTRAL databases (up to May 2016) to identify studies on epidermal grafting for wound healing. We will include any primary studies (excluding case reports or case series lesser than three patients) or systematic reviews of such studies to assess the outcome of epidermal grafting for wound healing either on its own or compared to other methods. The expected primary outcome measures are the efficacy of epidermal grafting for wound healing (measured by the proportion of wounds healed at 6 weeks) and the mean wound healing time (time for complete re-epithelialisation). Secondary outcome measures are the mean donor site-healing time, need for anaesthesia, costs associated with resource use, health-related quality of life, and proportion of patients with adverse event. Subgroup analysis will be performed for the proportions of wounds healed based on wound aetiology. DISCUSSION: This is a timely systematic review, and the finding of this systematic review is expected to guide research and clinical practice aimed at improving wound care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033051. PMID- 27255328 TI - Cross-National Variation in Glycemic Control and Diabetes-Related Distress Among East Asian Patients Using Insulin: Results from the MOSAIc Study. AB - INTRODUCTION: Guidelines recommend insulin progression for patients with type 2 diabetes (T2D) with inadequate glycemic control. The Multinational Observational Study Assessing Insulin use (MOSAIc [ClinicalTrials.gov identifier, NCT01400971]) study is a 2-year observational study, investigating factors that influence insulin progression in T2D patients. In this first of two reports, we describe baseline clinical and psychosocial characteristics of Chinese, Japanese, and South Korean patients who participated in MOSAIc. Insulin treatment, factors affecting progression, and outcomes will be reported separately. METHODS: Patients with T2D using insulin for >=3 months were eligible. Baseline demographic, clinical, and psychosocial data were collected from patients. Quality of life instruments, including the Diabetes Distress Scale (DDS), were used to assess patient's concerns about disease management, support, and emotional burden. The association between the DDS and the selected covariates was also assessed. RESULTS: A total of 373 patients in China, 157 in Japan, and 141 in South Korea were enrolled from July 2011 to July 2013. Mean +/- standard deviation duration (years) of T2D differed across countries (China 11.4 +/- 7.5; Japan 13.8 +/- 8.7; South Korea 15.7 +/- 8.8; P < 0.0001). Japanese patients used more noninsulin anti-hyperglycemic agents than did Chinese or South Korean patients (P < 0.0001). Exclusive use of basal insulin was most common in Japan and South Korea compared with China, whereas approximately 66.8% of Chinese patients used mixed insulin. Covariates associated with the DDS were younger age [P = 0.044 (Japan)], higher incidence of monthly hypoglycemia [P = 0.036 [China]; P = 0.021 (South Korea)], and male gender [P = 0.037 (South Korea)]. CONCLUSIONS: There were significant differences amongst East Asian patients with T2D treated with insulin, including in quality of life scores. Results from the MOSAIc longitudinal analyses will further investigate trends of insulin intensification and barriers to insulin progression. FUNDING: Eli Lilly and Company. PMID- 27255329 TI - Adapting HIV patient and program monitoring tools for chronic non-communicable diseases in Ethiopia. AB - BACKGROUND: Chronic non-communicable diseases (NCDs) have become a huge public health concern in developing countries. Many resource-poor countries facing this growing epidemic, however, lack systems for an organized and comprehensive response to NCDs. Lack of NCD national policy, strategies, treatment guidelines and surveillance and monitoring systems are features of health systems in many developing countries. Successfully responding to the problem requires a number of actions by the countries, including developing context-appropriate chronic care models and programs and standardization of patient and program monitoring tools. METHODS: In this cross-sectional qualitative study we assessed existing monitoring and evaluation (M&E) tools used for NCD services in Ethiopia. Since HIV care and treatment program is the only large-scale chronic care program in the country, we explored the M&E tools being used in the program and analyzed how these tools might be adapted to support NCD services in the country. Document review and in-depth interviews were the main data collection methods used. The interviews were held with health workers and staff involved in data management purposively selected from four health facilities with high HIV and NCD patient load. Thematic analysis was employed to make sense of the data. RESULTS: Our findings indicate the apparent lack of information systems for NCD services, including the absence of standardized patient and program monitoring tools to support the services. We identified several HIV care and treatment patient and program monitoring tools currently being used to facilitate intake process, enrolment, follow up, cohort monitoring, appointment keeping, analysis and reporting. Analysis of how each tool being used for HIV patient and program monitoring can be adapted for supporting NCD services is presented. CONCLUSION: Given the similarity between HIV care and treatment and NCD services and the huge investment already made to implement standardized tools for HIV care and treatment program, adaptation and use of HIV patient and program monitoring tools for NCD services can improve NCD response in Ethiopia through structuring services, standardizing patient care and treatment, supporting evidence-based planning and providing information on effectiveness of interventions. PMID- 27255330 TI - Mass testing and treatment for malaria in low transmission areas in Amhara Region, Ethiopia. AB - BACKGROUND: In areas with ongoing malaria transmission, strategies to clear parasites from populations can reduce infection and transmission. The objective of this paper was to describe a malaria mass testing and treatment (MTAT) intervention implemented in six kebeles (villages) in Amhara Region, Ethiopia, at the beginning of the 2014 transmission season. METHODS: Intervention kebeles were selected based on incidence of passively detected Plasmodium falciparum and mixed (P. falciparum and P. vivax) malaria cases during the 2013 malaria transmission season. All households in intervention kebeles were targeted; consenting residents received a rapid diagnostic test (RDT) and RDT-positive individuals received artemether-lumefantrine for P. falciparum/mixed infections or chloroquine for P. vivax. Data were collected on MTAT participation, sociodemographic characteristics, malaria risk factors, and RDT positivity. RESULTS: Of 9162 households targeted, 7974 (87.0 %) participated in the MTAT. Among the 35,389 residents of these households, 30,712 (86.8 %) received an RDT. RDT-positivity was 1.4 % (0.3 % P. vivax, 0.7 % P. falciparum, 0.3 % mixed), ranging from 0.3 to 5.1 % by kebele; 39.4 % of RDT-positive individuals were febrile, 28.5 % resided in the same household with another RDT-positive individual, 23.0 % were not protected by vector control interventions [mosquito net or indoor residual spray (IRS)], and 7.1 % had travel history. For individuals under 10 years of age, the odds of being RDT-positive was significantly higher for those with fever, recent use of anti-malarial drugs or residing in the same household with another RDT-positive individual; 59.0 % of RDT-positive individuals had at least one of these risk factors. For individuals 10 years of age and older, the odds of being RDT positive was significantly higher for those with reported travel, fever, recent use of anti-malarial drugs, no use of vector control, and those residing in the same household as another RDT positive individual; 71.2 % of RDT-positive individuals had at least one of these risk factors. CONCLUSIONS: In the Ethiopia setting, an MTAT intervention is operationally feasible and can be conducted with high coverage. RDT-positivity is low and varies widely by kebele. While several risk factors are significantly associated with RDT-positivity, there are still many RDT-positive individuals who do not have any of these risk factors. Strategies that target populations for testing and treatment based on these risk factors alone are likely to leave many infections undetected. PMID- 27255331 TI - Aspiration thrombectomy prior to percutaneous coronary intervention in ST elevation myocardial infarction: a systematic review and meta-analysis. AB - BACKGROUND: Trials of aspiration thrombectomy (AT) prior to primary percutaneous intervention (PCI) in patients with ST-segment elevation MI (STEMI) have shown apparently inconsistent results and therefore generated uncertainty and controversy. To summarize the effects of AT prior to PCI versus conventional PCI in STEMI patients. METHODS: Searches of MEDLINE, EMBASE and CENTRAL to June 2015 and review of reference lists of previous reviews. We included randomized controlled trials (RCTs) comparing AT prior to PCI with conventional PCI alone. Pairs of reviewers independently screened eligible articles; extracted data; and assessed risk of bias. We used the GRADE approach to rate overall certainty of the evidence. RESULTS: Among 73 potential articles identified, 20 trials including 21,660 patients were eligible; data were complete for 20,866 patients. Moderate-certainty evidence suggested a non statistically significant decrease in overall mortality (risk ratio (RR) 0.89, 95 % confidence interval, 0.78 to 1.01, risk difference (RD) 4/1,000 over 6 months), no impact on recurrent MI (RR 0.94, 95 % CI, 0.79 to 1.12) or major bleeding (RR 1.02, 95 % CI, 0.78 to 1.35), and an increase in stroke (RR 1.56, 95 % CI, 1.09 to 2.24, RD 3/1,000 over 6 months). CONCLUSIONS: Moderate certainty evidence suggests aspiration thrombectomy is associated with a possible small decrease in mortality (4 less deaths/1000 over 6 months) and a small increase in stroke (3 more strokes/1000 over 6 months). Because absolute effects are very small and closely balanced, thrombectomy prior to primary PCI should not be used as a routine strategy. PMID- 27255332 TI - Cardiac injury biomarkers in paediatric age: Are we there yet? AB - The aim of this article is to evaluate the clinical utility of cardiac injury biomarkers in paediatric age. In December 2015, a literature search was performed (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included the following medical subject headings and text terms for the key words: "cardiac injury biomarkers", "creatine kinase-MB", "myoglobin", "troponin", "children", "neonate/s", "newborn/s", "infant/s" and echocardiography. In the paediatric population, troponins show a good correlation with the extent of myocardial damage following cardiac surgery and cardiotoxic medication and can be used as predictors of subsequent cardiac recovery and mortality. Elevation of cardiac injury biomarkers may also have diagnostic value in cases when cardiac contusion or pericarditis is suspected. Cardiac injury biomarkers are very sensitive markers for the detection of myocardial injury and have been studied in healthy newborns, after tocolysis, intrauterine growth restriction, respiratory distress and asphyxia. The proportion of newborns with elevated troponin was higher than that in ill infants, children, and adolescents and in healthy adults, suggesting that myocardial injury, although clinically occult, is common in this young age group. Results suggest that significant elevation of cord troponin is an excellent early predictor of severity of hypoxic ischaemic encephalopathy and mortality in term infants. Cardiac biomarkers may also benefit centres without on-site echocardiography with evidence showing good correlation with echo-derived markers of myocardial function. Further studies are needed to better clarify the role of cardiac biomarkers in paediatric age and their correlation with echocardiographic parameters. PMID- 27255333 TI - The emergence of sarcoptic mange in Australian wildlife: an unresolved debate. AB - Due to its suspected increase in host range and subsequent global diversification, Sarcoptes scabiei has important implications at a global scale for wildlife conservation and animal and human health. The introduction of this pathogen into new locations and hosts has been shown to produce high morbidity and mortality, a situation observed recently in Australian and North American wildlife.Of the seven native animal species in Australia known to be infested by S. scabiei, the bare-nosed wombat (Vombatus ursinus) suffers the greatest with significant population declines having been observed in New South Wales and Tasmania. The origins of sarcoptic mange in Australian native animals are poorly understood, with the most consistent conclusion being that mange was introduced by settlers and their dogs and subsequently becoming a major burden to native wildlife. Four studies exist addressing the origins of mange in Australia, but all Australian S. scabiei samples derive from only two of these studies. This review highlights this paucity of phylogenetic knowledge of S. scabiei within Australia, and suggests further research is needed to confidently determine the origin, or multiple origins, of this parasite.At the global scale, numerous genetic studies have attempted to reveal how the host species and host geographic location influence S. scabiei phylogenetics. This review includes an analysis of the global literature, revealing that inconsistent use of gene loci across studies significantly influences phylogenetic inference. Furthermore, by performing a contemporary analytical approach on existing data, it is apparent that (i) new S. scabiei samples, (ii) appropriate gene loci targets, and (iii) advanced phylogenetic approaches are necessary to more confidently comprehend the origins of mange in Australia. Advancing this field of research will aid in understanding the mechanisms of spillover for mange and other parasites globally. PMID- 27255334 TI - Can Technology Improve the Quality of Colonoscopy? AB - In order for screening colonoscopy to be an effective tool in reducing colon cancer incidence, exams must be performed in a high-quality manner. Quality metrics have been presented by gastroenterology societies and now include higher adenoma detection rate targets than in the past. In many cases, the quality of colonoscopy can often be improved with simple low-cost interventions such as improved procedure technique, implementing split-dose bowel prep, and monitoring individuals' performances. Emerging technology has expanded our field of view and image quality during colonoscopy. We will critically review several technological advances in the context of quality metrics and discuss if technology can really improve the quality of colonoscopy. PMID- 27255335 TI - David Stanley Hinchcliff Cannon. PMID- 27255336 TI - Kernel machine score test for pathway analysis in the presence of semi-competing risks. AB - In cancer studies, patients often experience two different types of events: a non terminal event such as recurrence or metastasis, and a terminal event such as cancer-specific death. Identifying pathways and networks of genes associated with one or both of these events is an important step in understanding disease development and targeting new biological processes for potential intervention. These correlated outcomes are commonly dealt with by modeling progression-free survival, where the event time is the minimum between the times of recurrence and death. However, identifying pathways only associated with progression-free survival may miss out on pathways that affect time to recurrence but not death, or vice versa. We propose a combined testing procedure for a pathway's association with both the cause-specific hazard of recurrence and the marginal hazard of death. The dependency between the two outcomes is accounted for through perturbation resampling to approximate the test's null distribution, without any further assumption on the nature of the dependency. Even complex non-linear relationships between pathways and disease progression or death can be uncovered thanks to a flexible kernel machine framework. The superior statistical power of our approach is demonstrated in numerical studies and in a gene expression study of breast cancer. PMID- 27255338 TI - Cardiac Findings in the Fetus with Cerebral Arteriovenous Malformation Are Associated with Adverse Outcome. AB - OBJECTIVES: To assess cardiac sequelae of fetal cerebral arteriovenous malformations (CAVMs) and evaluate any association with outcomes. METHODS: We retrospectively analyzed cardiac structure and function in fetuses with CAVMs who underwent fetal echocardiography (October 1999 to August 2015, n = 11), and compared them with normal controls. RESULTS: The median gestational age was 36 weeks (range 18-38). Common abnormal findings included dilated superior vena cava (100%) and right atrium (82%), reduced middle cerebral artery pulsatility index (86%), tricuspid regurgitation (82%), and right ventricular (RV) dysfunction (64%). Hydrops was present in 1 fetus, who did not survive. The median cardiothoracic ratio (CTR) was 0.36 (0.29-0.45, n = 10); the median combined cardiac output indexed to estimated fetal weight (iCCO) was 565 ml/kg/min (379 1,565, n = 7). Of the 11 fetuses, 1 patient elected for termination, and 5 suffered neonatal demise. Comparing survivors (n = 5) and nonsurvivors (n = 6), a larger tricuspid valve (TV) z-score (p = 0.009) and RV dysfunction (p = 0.015) were associated with nonsurvival, and nonsurvivors had a higher iCCO than controls (990 vs. 550 ml/kg/min, p = 0.035). A larger difference between the TV and mitral valve z-scores (surrogate for RV dilation, p = 0.052), and CTR >0.38 (p = 0.0762) tended towards nonsurvival. CONCLUSION: CAVMs impose volume load on the fetal circulation, mainly affecting right heart structures. Increased right heart dilation and dysfunction are associated with nonsurvival. PMID- 27255337 TI - Functional Genomic Analysis of the Impact of Camelina (Camelina sativa) Meal on Atlantic Salmon (Salmo salar) Distal Intestine Gene Expression and Physiology. AB - The inclusion of plant meals in diets of farmed Atlantic salmon can elicit inflammatory responses in the distal intestine (DI). For the present work, fish were fed a standard fish meal (FM) diet or a diet with partial replacement of FM with solvent-extracted camelina meal (CM) (8, 16, or 24 % CM inclusion) during a 16-week feeding trial. A significant decrease in growth performance was seen in fish fed all CM inclusion diets (Hixson et al. in Aquacult Nutr 22:615-630, 2016). A 4x44K oligonucleotide microarray experiment was carried out and significance analysis of microarrays (SAM) and rank products (RP) methods were used to identify differentially expressed genes between the DIs of fish fed the 24 % CM diet and those fed the FM diet. Twelve features representing six known transcripts and two unknowns were identified as CM responsive by both SAM and RP. The six known transcripts (including thioredoxin and ependymin), in addition to tgfb, mmp13, and GILT, were studied using qPCR with RNA templates from all four experimental diet groups. All six microarray-identified genes were confirmed to be CM responsive, as was tgfb and mmp13. Histopathological analyses identified signs of inflammation in the DI of salmon fed CM-containing diets, including lamina propria and sub-epithelial mucosa thickening, infiltration of eosinophilic granule cells, increased goblet cells and decreased enterocyte vacuolization. All of these were significantly altered in 24 % CM compared to all other diets, with the latter two also altered in 16 % CM compared with 8 % CM and control diet groups. Significant correlation was seen between histological parameters as well as between five of the qPCR analyzed genes and histological parameters. These molecular biomarkers of inflammation arising from long-term dietary CM exposure will be useful in the development of CM-containing diets that do not have deleterious effects on salmon growth or physiology. PMID- 27255340 TI - US death rates rise slightly. PMID- 27255339 TI - The role of polyamines during exocarp formation in a russet mutant of 'Dangshansuli' pear (Pyrus bretschneideri Rehd.). AB - KEY MESSAGE: Differential genes of suberin, polyamine and transcription factors in transcriptome sequences and the contents of H 2 O 2 , spermidine, spermine, and putrescine changed significantly after treating with MGBG. Russeting is a commercially important process that restores the control of water loss through the skin via the formation of a waterproofing periderm just beneath the microcracked skin of pear primary fruit. A spontaneous russet skin mutant, the yellow-green 'Dangshansuli' pear, has been identified. To understand the role of polyamines in the formation of the russet skin of the mutant-type (MT) pear, it was treated with methylglyoxal-bis-(guanylhydrazone) (MGBG) for 4 weeks after full bloom. One week later, differentially expressed genes among the wild-type (WT), MT, and MGBG-treated MT pears were screened, hydrogen peroxide (H2O2) was localized using CeCl3, and the contents of H2O2 and polyamine were measured. A total of 57,086,772, 61,240,014, and 67,919,420 successful reads were generated from the transcriptomes of WT, MT, and MGBG-treated MT, with average unigene lengths of 701, 720, and 735 bp, respectively. Differentially expressed genes involved in polyamine metabolism and suberin synthesis were screened in 'Dangshansuli' and in the mutant libraries, and their relative expression was found to be significantly altered after treatment with MGBG, which was confirmed by real-time PCR. The expression patterns of differentially expressed transcription factors were identified and were found to be similar to those of the polyamine- and suberin-related genes. The results indicated that the H2O2 generated during polyamine metabolism might contribute to russet formation on the exocarp of the mutant pear. Furthermore, the contents of H2O2, spermidine, spermine, and putrescine and H2O2 localization provided a comprehensive transcriptomic view of russet formation in the mutant pear. PMID- 27255342 TI - Hybridization and de-hybridization between the locally-excited (LE) state and the charge-transfer (CT) state: a combined experimental and theoretical study. AB - Excited state properties play a key role in the photoluminescence (PL) and electroluminescence (EL) performance of organic light-emitting diode (OLED) materials. The solvatochromic effects were observed in a series of triphenylamine (TPA)-phenanthroimidazole (PI) derivatives with the increase of solvent polarity, accompanied by the transformation of an excited state character from the locally excited (LE) state to the charge-transfer (CT) state in the emission spectra. The excited state properties were systematically investigated in these donor-acceptor systems using time-dependent density functional theory (TD-DFT). The hybridization and de-hybridization processes between LE and CT states were resolved with an increasing number of phenyls along horizontal and vertical directions, respectively. We provide a novel insight into the fine modulation of the excited-state characters and compositions in the donor-acceptor system for the new-generation, low-cost and high-efficiency fluorescent OLED materials. PMID- 27255341 TI - Obesity and Pelvic Floor Disorders: A Review of the Literature. AB - Overweight and obesity are becoming a worldwide health problem associated with numerous co-morbidities. National costs of obesity and pelvic flor disorders have been rising since the 1950s across the world. Obesity is thought to have a very strong effect on pelvic floor disorders, and, considering the high prevalence of both problems worldwide, it is of utmost importance to evaluate the association between these pathologies as well as the impact of obesity on treatment efficacy. This review is based on a selection of reports in the literature (PubMed search), including guidelines and Cochrane reviews. Obesity seems to be a well-documented risk factor for lower urinary tract symptoms (LUTS) and is a predictor of exacerbation of stress urinary incontinence (SUI) and overactive bladder (OAB). Weight loss is also associated with improvement or resolution of SUI and OAB. In the case of pelvic organ prolapse (POP), weight loss is associated with improvement in quality of life. Although obesity is associated with POP in general, the exact role of obesity in symptomatic POP remains uncertain. While outcomes of anti-incontinence surgery among obese women are similar to those in non-obese women, postoperative urge incontinence is more likely to occur. It seems that obesity is not a risk factor for postoperative complications or short term efficacy of POP surgical treatment. Long-term effects are still uncertain. Obesity is a strong risk factor for LUTS, but in most cases it does not affect efficacy of operative treatment. It may be associated with some post-operative complications. Weight loss in many cases allows avoiding surgical intervention. PMID- 27255343 TI - Photo-induced in situ crosslinking of polymer brushes with dimethyl maleimide moieties for dynamically stimulating stem cell differentiation. AB - We designed photo-crosslinkable polymer brushes with dimethylmaleimide moieties, in order to demonstrate dynamic stimulation of cell differentiation in mesenchymal stem cells (MSCs). The polymer brushes were synthesized by surface initiated reversible addition fragmentation chain transfer polymerization using dimethylmaleimide ethyl methacrylate and methyl methacrylate on a chain transfer agent-immobilized glass surface. The polymer brushes were crosslinked by photodimerization of the dimethylmaleimide moieties within polymer chains with stem cells present on the surface. In order to evaluate the effects of in situ photo-induced crosslinking of the polymer brushes on gene expression of stem cells, human bone marrow MSCs were cultured under static and dynamic culture conditions for 7 days. Expression of the osteocalcin (Ocn) gene in MSCs was used as an indicator of osteoblast differentiation under dynamic culture conditions. Structural conversion from non-crosslinked polymer brushes to crosslinked polymer brushes increased the expression of Ocn by 1.4-fold in the presence of adhered cells, compared with non-crosslinked polymer brushes under static culture conditions. These results suggest that MSCs recognized surface conversion from non-crosslinked to crosslinked structures, which resulted in altered differentiation lineages. Therefore, photo-crosslinkable surfaces with dimethyl maleimide moieties are potential novel materials for dynamically stimulating MSC differentiation. PMID- 27255345 TI - Directional anisotropy, finite size effect and elastic properties of hexagonal boron nitride. AB - Classical molecular dynamics simulations have been performed to analyze the elastic and mechanical properties of two-dimensional (2D) hexagonal boron nitride (h-BN) using a Tersoff-type interatomic empirical potential. We present a systematic study of h-BN for various system sizes. Young's modulus and Poisson's ratio are found to be anisotropic for finite sheets whereas they are isotropic for the infinite sheet. Both of them increase with system size in accordance with a power law. It is concluded from the computed values of elastic constants that h BN sheets, finite or infinite, satisfy Born's criterion for mechanical stability. Due to the the strong in-plane sp2 bonds and the small mass of boron and nitrogen atoms, h-BN possesses high longitudinal and shear velocities. The variation of bending rigidity with system size is calculated using the Foppl-von Karman approach by coupling the in-plane bending and out-of-plane stretching modes of the 2D h-BN. PMID- 27255344 TI - Rhizorhabdus dicambivorans sp. nov., a dicamba-degrading bacterium isolated from compost. AB - Strain Ndbn-20T, a Gram-staining-negative, non-spore-forming bacterium, was isolated from compost of plant litter. The strain was able to degrade dicamba. Phylogenetic analysis based on 16S rRNA gene sequences indicated that Ndbn 20Trepresented a member of the family Sphingomonadaceae of the Alphaproteobacteria and showed high sequence similarities to Rhizorhabdusargentea SP1T (98.8 %), Sphingomonaswittichii RW1T (97.9 %), Sphingomonasstarnbergensis 382T (97.7 %) and Sphingomonashistidinilytica UM2T (97.7 %). However, the strain showed low DNA sequence relatedness with R. argentea SP1T (45.6+/-1.9 %), S. wittichii RW1T (33.5+/-2.3 %), S.histidinilytica UM2T (39.4+/-3.6 %) and S. starnbergensis382T (42.1+/-4.1 %). Ndbn-20T possessed Q-10 as the predominant ubiquinone, spermidine as the major polyamine, and summed feature 8 (comprising C18 : 1omega7c/C18 : 1omega6c), summed feature 3 (comprising C16 : 1omega7c/C16 : 1omega6c), C17 : 1omega6c, C16 : 0 and C14 : 02-OH as the major fatty acids (>5 % of the total). The profile of polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, glycolipid, sphingoglycolipid, phosphatidyldimethylethanolamine and phosphatidylglycerol. The DNA G+C content was 65.4 mol%. Based on a polyphasic taxonomic analysis, strain Ndbn-20T is proposed to represent a novel species of the genus Rhizorhabdus, with the proposed name of Rhizorhabdus dicambivorans sp. nov. The type strain is Ndbn-20T (=CCTCC AB 2016143=KACC 18661). PMID- 27255346 TI - Absence of galectin-3 promotes neuroprotection in retinal ganglion cells after optic nerve injury. AB - A trauma to the mature central nervous system (CNS) often leads to persistent deficits, due to the inability of axons to regenerate after being injured. Increasing evidence suggests that pro-inflammatory and pro-apoptotic genes can present a major obstacle to promoting neuroprotection of retinal ganglion cells and consequently succeed in axonal regeneration. This study evaluated the effect of the absence of galectin-3 (Gal-3) on retinal ganglion cells (RGC) survival and axonal regeneration/degeneration after optic nerve crush injury. Two weeks after crush there was a 2.6 fold increase in the rate of cell survival in Gal-3-/- mice (1283+/-79.15) compared to WT animals (495.4+/-53.96). However, no regeneration was observed in the Gal-3-/- mice two weeks after lesion. Furthermore, axonal degeneration presented a particular pattern on those mice; Electron Microscopy (EM) analysis showed incomplete axon degeneration while the WT mice presented an advanced stage of degeneration. This suggests that the removal of the nerve fibers in the Gal 3-/- mice could be deficient and this would cause a delay in the process of Wallerian degeneration once there is a decrease in the number of macrophages/microglia in the nerve. This study demonstrates how the absence of Gal-3 can affect RGC survival and optic nerve regeneration/degeneration after lesion. Our results suggest that the absence of Gal-3 plays an important role in the survival of RGC and thus can be a potential target for therapeutic intervention in RGC neuroprotection. PMID- 27255347 TI - Explaining frailty by lifestyle. AB - OBJECTIVE: To determine whether the effects of lifestyle factors on frailty can be adequately addressed by asking a single self-report question. DESIGN: Cross sectional study. SETTING: A sample of Dutch citizens completed the web-based questionnaire "Seniorenbarometer". PARTICIPANTS: 610 persons aged 50 years and older. MEASUREMENTS: Seven lifestyle factors were assessed: smoking, use of alcohol, intake of vegetables, intake of fruit, having breakfast, exercise, and teeth brushing. The single self-report question of lifestyle was: "Overall, how healthy would you say your lifestyle is?" Frailty was measured by the Tilburg Frailty Indicator. RESULTS: Age was positively associated with a healthy lifestyle (less smoking, more intake of vegetables, fruit and eating breakfast). The lifestyle factors did not improve the prediction of total, physical, psychological, and social frailty, after controlling for the single self-report question. CONCLUSION: Our study suggests that one general self-report lifestyle question, rather than a list of specific lifestyle factors, suffices for predicting frailty. PMID- 27255348 TI - Challenging the motor control of walking: Gait variability during slower and faster pace walking conditions in younger and older adults. AB - BACKGROUND: Gait variability is a measure of motor control of gait. Little is known about age-related changes in the motor control of gait (gait variability) during challenging walking conditions, such as slower and faster pace walking. OBJECTIVE: The purpose of this study was to examine the impact of challenging walking conditions (slower and faster speeds) on gait variability in younger and older adults. DESIGN: This study was a cross-sectional, observational design. METHODS: Forty younger (mean age=26.6+/-6.0years) and 111 community-dwelling older adults (mean age=77.3+/-6.0years), independent in ambulation, were studied. Gait characteristics were collected using a computerized walkway (GaitMat IITM). Step length, step width, step time, swing time, stance time and double support time variability were derived as the standard deviation of all steps across the 4 passes. RESULTS: Compared to younger, older adults had a significant change in their gait variability from usual to slower in step width (-0.006+/-0.003), step time (0.028+/-0.006), swing time (0.023+/-0.004), stance time (0.042+/-0.008), and double support time (0.024+/-0.005). Changes in gait variability from usual to faster were not significantly different between younger and older adults. LIMITATION: Gait variability was examined during self-selected over-ground walking, where subjects directed to walk "slower", "usual" and "faster". CONCLUSIONS: Walking slowly is more challenging to the motor control of gait and may be more sensitive to age-related declines in gait than usual and faster speed walks. PMID- 27255349 TI - Self-reported verbal abuse in 1300+ older women within a private, tertiary women's health clinic. AB - OBJECTIVE: Several studies describe "elder abuse" among residents of nursing homes, but this issue is less well studied among independently functioning, community-based women. The current study was undertaken to report rates of self reported intimate partner violence - with a focus on verbal abuse - among older women within a private tertiary women's health clinic. METHODS: This study focused on women who completed a questionnaire on domestic abuse. RESULTS: A total of 1389 women with a median age of 55 years (range: 50, 90) are the focus of this report. Most 1102 (79%) were married. Within this group, 100 (7%) women reported verbal abuse within the last year. Rates of physical and sexual abuse were much lower with 9 women (1%) and 2 (<1%), respectively. In univariate analyses, being divorced, being an alcoholic, and having suffered prior abuse were associated with reported verbal abuse. In multivariate analyses, self reported alcoholism and physical abuse were independently associated with reported verbal abuse. CONCLUSION: This study found a notable rate of patient reported verbal abuse in older women within a private, tertiary women's health clinic. IMPLICATIONS: This observation should prompt healthcare providers to ask about intimate partner violence - and specifically verbal abuse - regardless of healthcare setting. PMID- 27255350 TI - How Much Surface Coating of Hydrophobic Azithromycin Is Sufficient to Prevent Moisture-Induced Decrease in Aerosolisation of Hygroscopic Amorphous Colistin Powder? AB - Aerosolisation performance of hygroscopic particles of colistin could be compromised at elevated humidity due to increased capillary forces. Co-spray drying colistin with a hydrophobic drug is known to provide a protective coating on the composite particle surfaces against moisture-induced reduction in aerosolisation performance; however, the effects of component ratio on surface coating quality and powder aerosolisation at elevated relative humidities are unknown. In this study, we have systematically examined the effects of mass ratio of hydrophobic azithromycin on surface coating quality and aerosolisation performance of the co-spray dried composite particles. Four combination formulations with varying drug ratios were prepared by co-spray drying drug solutions. Both of the drugs in each combination formulation had similar in vitro deposition profiles, suggesting that each composite particle comprises two drugs in the designed mass ratio, which is supported by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) data. XPS and ToF-SIMS measurements also revealed that 50% by weight (or 35% by molecular fraction) of azithromycin in the formulation provided a near complete coating of 96.5% (molar fraction) on the composite particle surface, which is sufficient to prevent moisture-induced reduction in fine particle fraction (FPF)recovered and FPFemitted. Higher azithromycin content did not increase coating coverage, while contents of azithromycin lower than 20% w/w did not totally prevent the negative effects of humidity on aerosolisation performance. This study has highlighted that a critical amount of azithromycin is required to sufficiently coat the colistin particles for short-term protection against moisture. PMID- 27255351 TI - [Current situation on fertility preservation in cancer patients in Spain: Level of knowledge, information, and professional involvement]. AB - INTRODUCTION: The estimated risks of infertility in childhood cancer due to radiation, chemotherapy and surgery are well known. The involvement of professionals and advances in the different methods of preservation are increasing. However, many patients do not receive information or perform any method of preservation. MATERIAL: Questionnaires to paediatric onco-haematology institutions throughout Spain. The questionnaire consisted of 22 questions assessing their usual practices and knowledge about fertility preservation. RESULTS: Fifty members of the Spanish Society of Paediatric Haematology and Oncology, representing 24 of 43 centres, responded. These represented 82% of centres that treated higher numbers of patients. The effect of treatment on fertility was known by 78% of those who responded, with 76% admitting not knowing any guideline on fertility in children or adolescents. As for the ideal time and place to inform the patient and/or family, only 14% thought it should be done in the same cancer diagnosis interview. In clinical practice, 12% of those surveyed never referred patients to Human Reproduction Units, another 12% only did so if the patients showed interest, and 38% only refer patients in puberty. Just over one-third (34%) of those referrals were going to receive highly gonadotoxic treatment. CONCLUSIONS: There are clear differences between pre-puberty and puberty patients. The frequency with which some method of fertility preservation is performed in patients is low. All respondents believe that the existence of national guidelines on the matter would be of interest. PMID- 27255352 TI - [Patient experience in emergency departments: What do children and adolescents think?] AB - INTRODUCTION: Improving patient experience must become a priority in paediatric emergency departments. This experience is often studied by surveying parents, and not children directly. The aim of this study was to assess the patient experience of children attended in a Paediatric Emergency Department (PED). PATIENTS AND METHODS: A prospective descriptive study was conducted using a survey based on the Picker questionnaire on the patient experience. From January to May 2014, children 8-17 years seen in the Paediatric Emergency Department and admitted to the hospital were asked to complete the questionnaires anonymously, within 24hours of admission. RESULTS: A total of 217 patients completed the survey. The responses showed the 19.4% had to wait longer than expected, with 46.2% saying that there was not enough for children of their age group to do while waiting to be seen. As regards care and treatment, 4.6% of participants said staff did not fully explain what they were doing, and 23% said that they were not given enough privacy when being examined. Overall, 99.1% of patients said that they were well treated. CONCLUSIONS: Overall patient experience in the PED was positive. Some aspects have to be improved (activities in the waiting room, and privacy during the examination). PMID- 27255353 TI - CORRELATIONS BETWEEN INTELLIGENCE, HEAD CIRCUMFERENCE AND HEIGHT: EVIDENCE FROM TWO SAMPLES IN SAUDI ARABIA. AB - This study was based on two independent studies which in total consisted of 1812 school pupils aged 6-12 years in Saudi Arabia. Study I consisted of 1591 school pupils (609 boys and 982 girls) attending state schools, and Study II consisted of 211 boys with learning disabilities. Intelligence (measured using the Standard Progressive Matrices Plus for Study I and the Standard Progressive Matrices for Study II), head size and height were measured for the two samples. The results showed that intelligence was statistically significantly correlated with head circumference (r=0.350, p<0.001 for Study I and r=0.168, p<0.05 for Study II) and height (r=0.271, p<0.001 for Study I and r=0.178, p<0.05 for Study II). PMID- 27255354 TI - Association of Pentraxin 3 with Autoimmune Diseases: A Systematic Review and Meta Analysis. AB - BACKGROUND AND AIMS: Pentraxin 3 (PTX3) plays an important role in the inflammatory processes. Recently it has been reported to be involved in autoimmune diseases. Many studies have investigated the serum/plasma levels of PTX3 in autoimmune diseases, but the results are contradictory or inconclusive among those findings. The purpose of this meta-analysis was to investigate whether serum/plasma levels of PTX3 were associated with autoimmune diseases by comparing the serum/plasma levels of PTX3 in the autoimmune diseases and healthy controls. METHODS: PubMed, ELSEVIER ScienceDirect and Cochrane Library databases (up to December 26, 2015) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random effect model analysis. RESULTS: A total of 20 studies including seven studies of systemic lupus erythematosus (SLE), four studies of ankylosing spondylitis (AS), five studies of rheumatoid arthritis (RA), three studies of systemic sclerosis (SSc) and one study of multiple sclerosis (MS) were finally included in the meta analysis. The results revealed that the serum/plasma levels of PTX3 in autoimmune diseases were significantly higher than in normal controls (SMD = 0.496 ng/mL, 95% CI = 0.107-0.886, p <0.001; I(2) = 91.9, p <0.001). The subgroup analysis showed that the serum/plasma levels of PTX3 in AS and SSc were higher than in healthy controls (pooled SMD = 0.926 ng/mL, 95% CI = 0.174-1.677, p <0.001, I(2) = 77.0, p = 0.013; pooled SMD = 0.546 ng/mL, 95% CI = 0.136-0.957, p <0.001; I(2) = 30.9, p = 0.299, respectively). CONCLUSIONS: Serum/plasma levels of PTX3 in autoimmune diseases were higher than in normal controls. PMID- 27255355 TI - Does the Serum Metallothionein Level Reflect the Stage of Testicular Germ Cell Tumor? AB - Increased levels of metallothionein (MT) have recently been found in the blood serum of men with newly diagnosed testicular germ cell tumors (TGCT). In light of previously published results, the aim of this study was to investigate the difference in serum MT levels among patients with different stages of TGCT and compare MT with commonly used markers (alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase). The concentration of total MT was determined in the serum of 25 men with TGCT (seminoma or non-seminoma) by differential pulse voltammetry. Serum samples were obtained prior to chemotherapy, after two cycles of chemotherapy and 1 year after chemotherapy. A statistically significant difference in MT levels in patients with different stages of TGCT was observed in the serum of patients with non-seminoma obtained before chemotherapy. Although not significant, an increase in serum MT levels commensurate with the disease stage increase was also observed in patients with seminomatous TGCT. The results indicate that, in combination with the existing markers, MT could be useful for the identification of the histological type of tumor and stage of the disease before biopsy diagnosis. PMID- 27255356 TI - CD147 and matrix-metalloproteinase-2 expression in metastatic and non-metastatic uveal melanomas. AB - BACKGROUND: Extracellular matrix remodelling regulated by matrix metalloproteinase (MMP) inducer (CD147) is a crucial process during tumor cell invasion and regulation of blood supply. In this study, we evaluated the correlation of CD147 and MMP-2 expression with major prognostic factors for uveal melanoma and the development of metastasis. METHODS: The expression of CD147 and MMP-2 was analyzed in 49 samples of uveal melanomas. Triple immunofluorescence stainings using markers against glial cells (GFAP), endothelial cells (CD34) and macrophages (CD68) were performed to further analyse the exact localisation of CD147 and MMP-2 positivity. In 28 cases clinical metastatic disease were found. The remaining 21 cases showed no signs of metastatic disease for an average follow-up of 10 years. Correlation analysis (Pearson correlation) was performed to analyse the association of CD147 and MMP-2 expression with known prognostic factors, vasculogenic mimicry (VM), the mature vasculature (von Willebrand Factor) and tumor induced angiogenesis (by means of Endoglin expression). RESULTS: CD147 and MMP-2 were expressed in 47 (96.0 %) of the uveal melanomas. CD147 up-regulation was significantly correlated with a higher MMP-2 expression. The overall expression analysis revealed no significant difference in the metastatic (p = 0.777) and non-metastatic subgroup (p = 0.585). No correlation of CD147 expression and any system of blood supply was evident. In the non metastatic sub-group a significant correlation of clustered CD147 positive cells with largest basal diameter (p = 0.039), height (p = 0.047) and TNM-stage (p = 0.013) was evident. CONCLUSIONS: These data may indicate that CD147 regulates MMP 2 expression in uveal melanoma cells. PMID- 27255357 TI - Response to letter to the editor, "Lung cancer stigma and patient-provider communication: A complex association". PMID- 27255358 TI - Structural determinants of hydration, mechanics and fluid flow in freeze-dried collagen scaffolds. AB - Freeze-dried scaffolds provide regeneration templates for a wide range of tissues, due to their flexibility in physical and biological properties. Control of structure is crucial for tuning such properties, and therefore scaffold functionality. However, the common approach of modeling these scaffolds as open cell foams does not fully account for their structural complexity. Here, the validity of the open-cell model is examined across a range of physical characteristics, rigorously linking morphology to hydration and mechanical properties. Collagen scaffolds with systematic changes in relative density were characterized using Scanning Electron Microscopy, X-ray Micro-Computed Tomography and spherical indentation analyzed in a time-dependent poroelastic framework. Morphologically, all scaffolds were mid-way between the open- and closed-cell models, approaching the closed-cell model as relative density increased. Although pore size remained constant, transport pathway diameter decreased. Larger collagen fractions also produced greater volume swelling on hydration, although the change in pore diameter was constant, and relatively small at ~6%. Mechanically, the dry and hydrated scaffold moduli varied quadratically with relative density, as expected of open-cell materials. However, the increasing pore wall closure was found to determine the time-dependent nature of the hydrated scaffold response, with a decrease in permeability producing increasingly elastic rather than viscoelastic behavior. These results demonstrate that characterizing the deviation from the open-cell model is vital to gain a full understanding of scaffold biophysical properties, and provide a template for structural studies of other freeze-dried biomaterials. STATEMENT OF SIGNIFICANCE: Freeze-dried collagen sponges are three-dimensional microporous scaffolds that have been used for a number of exploratory tissue engineering applications. The characterization of the structure-properties relationships of these scaffolds is necessary to understand their biophysical behavior in vivo. In this work, the relationship between morphology and physical properties in the dry and hydrated states was investigated across a range of solid concentrations in the scaffolds. The quantitative results provided can aid the design of scaffolds with a target trade-off between mechanical properties and structural features important for their biological activity. PMID- 27255359 TI - Extracorporeal shock wave therapy does not improve hypertensive nephropathy. AB - Low-energy extracorporeal shock wave therapy (SWT) has been shown to improve myocardial dysfunction, hind limb ischemia, erectile function, and to facilitate cell therapy and healing process. These therapeutic effects were mainly due to promoting angiogenesis. Since chronic kidney diseases are characterized by renal fibrosis and capillaries rarefaction, they may benefit from a proangiogenic treatment. The objective of our study was to determine whether SWT could ameliorate renal repair and favor angiogenesis in L-NAME-induced hypertensive nephropathy in rats. SWT was started when proteinuria exceeded 1 g/mmol of creatinine and 1 week after L-NAME removal. SWT consisted of implying 0.09 mJ/mm(2) (400 shots), 3 times per week. After 4 weeks of SWT, blood pressure, renal function and urinary protein excretion did not differ between treated (LN + SWT) and untreated rats (LN). Histological lesions including glomerulosclerosis and arteriolosclerosis scores, tubular dilatation and interstitial fibrosis were similar in both groups. In addition, peritubular capillaries and eNOS, VEGF, VEGF R, SDF-1 gene expressions did not increase in SWT-treated compared to untreated animals. No procedural complications or adverse effects were observed in control (C + SWT) and hypertensive rats (LN + SWT). These results suggest that extracorporeal kidney shock wave therapy does not induce angiogenesis and does not improve renal function and structure, at least in the model of hypertensive nephropathy although the treatment is well tolerated. PMID- 27255360 TI - Vascular flow reserve as a link between long-term blood pressure level and physical performance capacity in mammals. AB - Mean arterial pressure (MAP) is surprisingly similar across different species of mammals, and it is, in general, not known which factors determine the arterial pressure level. Mammals often have a pronounced capacity for sustained physical performance. This capacity depends on the vasculature having a flow reserve that comes into play as tissue metabolism increases. We hypothesize that microvascular properties allowing for a large vascular flow reserve is linked to the level of the arterial pressure.To study the interaction between network properties and network inlet pressure, we developed a generic and parsimonious computational model of a bifurcating microvascular network where diameter and growth of each vessel evolves in response to changes in biomechanical stresses. During a simulation, the network develops well-defined arterial and venous vessel characteristics. A change in endothelial function producing a high precapillary resistance and thus a high vascular flow reserve is associated with an increase in network inlet pressure. Assuming that network properties are independent of body mass, and that inlet pressure of the microvascular network is a proxy for arterial pressure, the study provides a conceptual explanation of why high performing animals tend to have a high MAP. PMID- 27255361 TI - Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice. AB - Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice. PMID- 27255362 TI - What approaches to social prescribing work, for whom, and in what circumstances? A protocol for a realist review. AB - BACKGROUND: The use of non-drug, non-health-service interventions has been proposed as a cost-effective alternative to help those with long-term conditions manage their illness and improve their health and well-being. Interventions typically involve accessing activities run by the third sector or community agencies and may also be described as non-medical referral, community referral or social prescribing. To be effective, patients need to be "transferred" from the primary care setting into the community and to maintain their participation in activities. However, it is not currently known how and why these approaches enable which people under what circumstances to reach community services that may benefit their health and well-being. METHODS: Database searches and extensive searching of grey sources will be carried out in an attempt to find evidence associated with referral and retention in social prescribing. After initial scoping searches, two main phases of searching will be conducted: (a) will focus on the identification of programme theories to illustrate how approaches to social prescribing work for different people and in different contexts and (b) will consist of targeted searches to locate evidence to refine these candidate theories into configurations of the contexts in which populations and the main mechanisms outcomes are achieved. Inclusion criteria will initially be broad in order to develop a clear picture of the ways in which social prescriptions might operate but may iteratively become more focused in response to initially identified evidence, for example, in terms of the population group. An expert advisory group consisting of professionals working in a range of organisations involved in social prescribing will be convened to check the approaches in the review and provide real-life experience of social prescribing. Findings from the review will be disseminated to commissioners, published in a peer-reviewed journal and used to help refine an intervention model for an outdoor nature-based group intervention. DISCUSSION: This realist review will explore why mechanisms of social prescribing work, for what groups of people and their impact on enrolment, attendance and adherence to programmes. The use of realist approaches to detail the social prescribing process is novel and will offer insights into effective transfer of patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016039491. PMID- 27255363 TI - Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): I. Seasonal patterns and effects of stress and adrenocorticotropic hormone. AB - The secretion of steroids from the adrenal gland is a classic endocrine response to perturbations that can affect homeostasis. During an acute stress response, glucocorticoids (GC), such as corticosterone (CORT), prepare the metabolic physiology and cognitive abilities of an animal in a manner that promotes survival during changing conditions. Although GC functions during stress are well established, much less is understood concerning how adrenal androgens, namely dehydroepiandrosterone (DHEA) are influenced by stress. I conducted three field studies (one experimental and two descriptive) aimed at identifying how both CORT and DHEA secretion in free-living male northern cardinals (Cardinalis cardinalis), vary during acute stress; across different circulations (brachial vs. jugular); in response to ACTH challenge; and during the annual cycle. As predicted, restraint stress increased plasma CORT, but unexpectedly DHEA levels decreased, but the latter effect was only seen for blood sampled from the jugular vein, and not the brachial. The difference in DHEA between circulations may result from increased neural uptake of DHEA during stress. Injection with exogenous adrenocorticotropic hormone (ACTH) increased CORT concentrations, but failed to alter DHEA levels, thus suggesting ACTH is not a direct regulator of DHEA. Monthly field sampling revealed distinct seasonal patterns to both initial and restraint stress CORT and DHEA levels with distinct differences in the steroid milieu between breeding and non-breeding seasons. These data suggest that the CORT response to stress remains relatively consistent, but DHEA secretion is largely independent of the response by CORT. Although CORT functions have been well-studied in wild animals, little research exists for the role of DHEA and their variable relationship sets the stage for future experimental research addressing steroid stress responses. PMID- 27255364 TI - Expression of insulin-like growth factors at mRNA levels during the metamorphic development of turbot (Scophthalmus maximus). AB - Insulin-like growth factors I and II (IGF-I and IGF-II) are important regulators of vertebrate growth and development. This study characterized the mRNA expressions of igf-i and igf-ii during turbot (Scophthalmus maximus) metamorphosis to elucidate the possible regulatory role of the IGF system in flatfish metamorphosis. Results showed that the mRNA levels of igf-i significantly increased at the early-metamorphosis stage and then gradually decreased until metamorphosis was completed. By contrast, mRNA levels of igf-ii significantly increased at the pre-metamorphosis stage and then substantially decreased during metamorphosis. Meanwhile, the whole-body thyroxine (T4) levels varied during larval metamorphosis, and the highest value was observed in the climax-metamorphosis. The mRNA levels of igf-i significantly increased and decreased by T4 and thiourea (TU, inhibitor of endogenous thyroid hormone) during metamorphosis, respectively. Conversely, the mRNA levels of igf-ii remained unchanged. Furthermore, TU significantly inhibited the T4-induced mRNA up regulation of igf-i during metamorphosis. The whole-body thyroxine (T4) levels were significantly increased and decreased by T4 and TU during metamorphosis, respectively. These results suggested that igf-i and igf-ii may play different functional roles in larval development stages, and igf-i may have a crucial function in regulating the early metamorphic development of turbot. These findings may enhance our understanding of the potential roles of the IGF system to control flatfish metamorphosis and contribute to the improvement of broodstock management for larvae. PMID- 27255365 TI - Development of a homologous radioimmunoassay for red seabream follicle stimulating hormone and regulation of gonadotropins by GnRH in red seabream, Pagrus major. AB - Using a recombinant chimeric single-chain follicle stimulating hormone (FSH), we established a radioimmunoassay (RIA) for red seabream (Pagrus major) FSH (pmFSH) which became a powerful tool for studying reproductive physiology. We studied the profiles in plasma and pituitary concentrations of FSH and luteinizing hormone (LH) during sexual maturation. A pre-established RIA for red seabream LH was used for the LH measurements. The regulation of FSH and LH secretion from the pituitary was investigated using a gonadotropin-releasing hormone analog (GnRHa) in vivo and in vitro. Marked differences in plasma and pituitary FSH levels were observed between males and females; pituitary FSH content in males was much higher than that in females during all seasons, and plasma FSH levels in males were high during the spawning season, whereas those in females were unchanged. In contrast, plasma and pituitary levels of LH were elevated before and during the spawning season in males and females. Injecting or implanting (cholesterol pellet) a GnRHa into adult and juvenile red seabream resulted in significant increases in plasma LH concentrations; however, no significant change was observed in plasma FSH. Moreover, GnRHa stimulated only LH secretion in an in vitro experiment using dispersed pituitary cells. The discrete FSH and LH secretion profiles revealed suggest differential roles for the two gonadotropins during red seabream gametogenesis. In addition, the marked difference in pituitary FSH levels in males and females suggests the relative significance of FSH in male reproduction. PMID- 27255366 TI - Temperature-induced variation in yolk androgen and thyroid hormone levels in avian eggs. AB - Global warming has substantially changed the environment, but the mechanisms to cope with these changes in animals, including the role of maternal effects, are poorly understood. Maternal effects via hormones deposited in eggs, have important environment-dependent effects on offspring development and fitness: thus females are expected to adjust these hormones to the environment, such as the ambient temperature. Longer-term temperature variation could function as a cue, predicting chick rearing conditions to which yolk hormone levels are adjusted, while short-term temperature variation during egg formation may causally affect hormone transfer to eggs. We studied the effects of ambient temperature on yolk androgens (testosterone and androstenedione) and thyroid hormones (thyroxine and triiodothyronine) in great tits (Parus major) using data from unmanipulated clutches from a wild population and from aviary birds (ad libitum food) exposed to different experimental temperature treatments during five years. Both in the wild and in captivity, longer-term pre-laying ambient temperature was not associated with clutch mean yolk hormone levels, while the way androstenedione and thyroxine levels varied across the laying sequence did associate with pre-laying temperature in the wild. Yolk testosterone levels were positively correlated with short-term temperature (during yolk formation) changes within clutches in both wild and captivity. We also report, for the first time in a wild bird, that yolk thyroxine levels correlated with a key environmental factor: thyroxine levels were negatively correlated with ambient temperature during egg formation. Thus, yolk hormone levels, especially testosterone, seem to be causally affected by ambient temperature. These short-term effects might reflect physiological changes in females with changes in ambient temperature. The adaptive value of the variation with ambient temperatures pre-laying or during egg formation should be studied with hormone manipulations in different thermal environments. PMID- 27255367 TI - Sources of variation in plasma corticosterone and dehydroepiandrosterone in the male northern cardinal (Cardinalis cardinalis): II. Effects of urbanization, food supplementation and social stress. AB - Perturbations in an organism's environment can induce significant shifts in hormone secretory patterns. In this context, the glucocorticoid (GC) steroids secreted by the adrenal cortex have received much attention from ecologists and behaviorists due to their role in the vertebrate stress response. Adrenal GCs, such as corticosterone (CORT), are highly responsive to instability in environmental and social conditions. However, little is understood about how adrenal dehydroepiandrosterone (DHEA) is influenced by changing conditions. We conducted field experiments to determine how circulating CORT and DHEA vary during restraint stress in the male northern cardinals (Cardinalis cardinalis). Specifically, we examined how four different changes in the physical (urbanization and food availability) and social (territorial conflict, distress of a mate) environment affect CORT and DHEA levels. The majority of cardinals responded to restraint stress by increasing and decreasing CORT and DHEA, respectively, however this depended on sampling context. Cardinals sampled from urban habitats had both lower initial and restraint stress CORT concentrations, but a comparable DHEA pattern to those sampled from a forest. Supplementing food to territorial males did not alter circulating initial DHEA or CORT concentrations nor did it change the response to restraint stress when compared to unsupplemented controls. Exposing cardinals to varying durations of song playback, which mimics a territorial intrusion, did not affect CORT levels, but did attenuate the DHEA response to restraint stress. Examining a larger dataset of males captured before, after or at the same time as their female mate, allowed us to address how the stress of a captured mate affected the male's CORT and DHEA response. Males showed elevated initial and restraint CORT and DHEA when their female mate was captured first. Taken together, these data demonstrate that both CORT and DHEA secretion patterns depends on environmental, and particularly current social conditions. PMID- 27255368 TI - Effects of thyroid endocrine manipulation on sex-related gene expression and population sex ratios in Zebrafish. AB - Thyroid hormone reportedly induces masculinization of genetic females and goitrogen treatment delays testicular differentiation (ovary-to-testis transformation) in genetic males of Zebrafish. This study explored potential molecular mechanisms of these phenomena. Zebrafish were treated with thyroxine (T4, 2nM), goitrogen [methimazole (MZ), 0.15mM], MZ (0.15mM) and T4 (2nM) (rescue treatment), or reconstituted water (control) from 3 to 33days postfertilization (dpf) and maintained in control water until 45dpf. Whole fish were collected during early (25dpf) and late (45dpf) testicular differentiation for transcript abundance analysis of selected male (dmrt1, amh, ar) and female (cyp19a1a, esr1, esr2a, esr2b) sex-related genes by quantitative RT-PCR, and fold-changes relative to control values were determined. Additional fish were sampled at 45dpf for histological assessment of gonadal sex. The T4 and rescue treatments caused male biased populations, and T4 alone induced precocious puberty in ~50% of males. Male-biased sex ratios were accompanied by increased expression of amh and ar and reduced expression of cyp19a1a, esr1, esr2a, and esr2b at 25 and 45dpf and, unexpectedly, reduced expression of dmrt1 at 45dpf. Goitrogen exposure increased the proportion of individuals with ovaries (per previous studies interpreted as delay in testicular differentiation of genetic males), and at 25 and 45dpf reduced the expression of amh and ar and increased the expression of esr1 (only at 25dpf), esr2a, and esr2b. Notably, cyp19a1a transcript was reduced but via non thyroidal pathways (not restored by rescue treatment). In conclusion, the masculinizing activity of T4 at the population level may be due to its ability to inhibit female and stimulate male sex-related genes in larvae, while the inability of MZ to induce cyp19a1a, which is necessary for ovarian differentiation, may explain why its "feminizing" activity on gonadal sex is not permanent. PMID- 27255369 TI - Hyperoside reduces albuminuria in diabetic nephropathy at the early stage through ameliorating renal damage and podocyte injury. AB - Diabetic nephropathy (DN) is one of the major microvascular complications in diabetes. Podocyte injury such as slit diaphragm effacement is regarded as a determinant in the occurrence and development of albuminuria in DN. In this study, we examined the effect of hyperoside, an active flavonoid glycoside, on proteinuria and renal damage in a streptozotocin-induced DN mouse model at the early stage. The results showed that oral administration of hyperoside (30 mg/kg/day for 4 weeks could significantly decrease urinary microalbumin excretion and glomerular hyperfiltration in DN mice, but did not affect the glucose and lipid metabolism. Periodic acid-Schiff staining and transmission electron microscopy showed that glomerular mesangial matrix expansion and podocyte process effacement in DN mice were significantly improved by hyperoside. Further investigations via immunofluorescence staining, real-time reverse transcription polymerase chain reaction and Western blot analysis showed that the decreased slit diaphragm protein nephrin and podocin mRNA expression and protein levels in DN mice were restored by hyperoside treatment. Collectively, these findings demonstrated that hyperoside could decrease albuminuria at the early stage of DN by ameliorating renal damage and podocyte injury. PMID- 27255371 TI - Application of oleosin-flanked keratinocyte growth factor-2 expressed from Arabidopsis thaliana promotes hair follicle growth in mice. AB - OBJECTIVE: To determine an efficient expression strategy in Arabidopsis thaliana and to determine whether a dimeric oleosin fusion approach could achieve keratinocyte growth factor-2 (KGF2) expression and bioactivity. RESULTS: Higher recombinant protein accumulation was observed in the two dimeric oleosin constructs than in a single-oleosin-fused protein (O::KGR2) or KGF2 control. Highest expression was in O-O::KGF2-transgenic seeds. MTT assay in FGFR2 III b BaF3 cells revealed comparable levels of bioactivity due to O-O::KGF2 and O::KGR2, whereas O::KGF2-O had no effect on FGFR2 III b-BaF3 opithelial cell growth. The transgenic proteins had a pronounced stimulatory effect on hair follicle proliferation in C57BL/6 mice. CONCLUSION: A dimeric oleosin approach can be used to express KGF2 with the non-symmetrical O-O::KGF2 construct showing the highest expression and bioactivity. PMID- 27255370 TI - Towards sustainable partnerships in global health: the case of the CRONICAS Centre of Excellence in Chronic Diseases in Peru. AB - Human capital requires opportunities to develop and capacity to overcome challenges, together with an enabling environment that fosters critical and disruptive innovation. Exploring such features is necessary to establish the foundation of solid long-term partnerships. In this paper we describe the experience of the CRONICAS Centre of Excellence in Chronic Diseases, based at Universidad Peruana Cayetano Heredia in Lima, Peru, as a case study for fostering meaningful and sustainable partnerships for international collaborative research. The CRONICAS Centre of Excellence in Chronic Diseases was established in 2009 with the following Mission: "We support the development of young researchers and collaboration with national and international institutions. Our motivation is to improve population's health through high quality research." The Centre's identity is embedded in its core values - generosity, innovation, integrity, and quality- and its trajectory is a result of various interactions between multiple individuals, collaborators, teams, and institutions, which together with the challenges confronted, enables us to make an objective assessment of the partnership we would like to pursue, nurture and support. We do not intend to provide a single example of a successful partnership, but in contrast, to highlight what can be translated into opportunities to be faced by research groups based in low- and middle-income countries, and how these encounters can provide a strong platform for fruitful and sustainable partnerships. In defiant contexts, partnerships require to be nurtured and sustained. Acknowledging that all partnerships are not and should not be the same, we also need to learn from the evolution of such relationships, its key successes, hurdles and failures to contribute to the promotion of a culture of global solidarity where mutual goals, mutual gains, as well as mutual responsibilities are the norm. In so doing, we will all contribute to instil a new culture where expectations, roles and interactions among individuals and their teams are horizontal, the true nature of partnerships. PMID- 27255372 TI - Application of phosphatidylethanol (PEth) in whole blood in comparison to ethyl glucuronide in hair (hEtG) in driving aptitude assessment (DAA). AB - For driving aptitude assessment (DAA), the analysis of several alcohol biomarkers is essential for the detection of alcohol intake besides psycho-medical exploration. In Switzerland, EtG in hair (hEtG) is often the only direct marker for abstinence monitoring in DAA. Therefore, the suitability of phosphatidylethanol (PEth) was investigated as additional biomarker. PEth 16:0/18:1 and 16:0/18:2 were determined by online-SPE-LC-MS/MS in 136 blood samples of persons undergoing DAA and compared to hEtG, determined in hair segments taken at the same time. With a PEth 16:0/18:1 threshold of 210 ng/mL for excessive alcohol consumption, all (n = 30) but one tested person also had hEtG values >=30 pg/mg. In 54 cases, results are not in contradiction to an abstinence as neither PEth (<20 ng/mL) nor hEtG (<7 pg/mg) was detected. In eight cases, both markers showed moderate consumption. Altogether, PEth and hEtG were in accordance in 68 % of the samples, although covering different time periods of alcohol consumption. With receiver operating characteristic analysis, PEth was evaluated to differentiate abstinence, moderate, and excessive alcohol consumption in accordance with hEtG limits. A PEth 16:0/18:1 threshold of 150 ng/mL resulted in the best sensitivity (70.6 %) and specificity (98.8 %) for excessive consumption. Values between 20 and 150 ng/mL passed for moderate consumption, values <20 ng/mL passed for abstinence. As PEth mostly has a shorter detection window (2-4 weeks) than hEtG (up to 6 months depending on hair length), changes in drinking behavior can be detected earlier by PEth than by hEtG analysis alone. Therefore, PEth helps to improve the diagnostic information and is a valuable additional alcohol marker for DAA. PMID- 27255373 TI - Pharmacological treatment of hypertension and hyperlipidemia in Izhevsk, Russia. AB - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in Russia. Hypertension and hyperlipidemia are important risk factors for CVD that are modifiable by pharmacological treatment and life-style changes. We aimed to characterize the extent of the problem in a typical Russian city by examining the prevalence, treatment and control rates of hypertension and hyperlipidemia and investigating whether the specific pharmacological regimes used were comparable with guidelines from a country with much lower CVD rates. METHODS: The Izhevsk Family Study II included a cross-sectional survey of a population sample of 1068 men, aged 25-60 years conducted in Izhevsk, Russia (2008-2009). Blood pressure and total cholesterol were measured and self-reported medication use was recorded by a clinician. We compared drug treatments with the Russian and Canadian treatment guidelines for hypertension and hyperlipidemia. RESULTS: The prevalence of hypertension was 61 % (age-standardised prevalence 51 %), with 66 % of those with hypertension aware of their diagnosis and 50 % of those aware taking treatment. 17 % of those taking treatment achieved blood pressure control. The majority (59 %) of those taking treatment were not doing so regularly. Prevalence of hyperlipidemia was 45 % (age-standardised prevalence 40 %), however less than 2 % of those with hyperlipidemia were taking any treatment. Types of lipid lowering and anti-hypertensive medications prescribed were broadly in line with Russian and Canadian guidelines. CONCLUSION: The prevalence of hypertension and hyperlipidemia is high in Izhevsk while the proportion of those treated and attaining treatment targets is very low. Prescribed medications were concurrent with those in Canada, but adherence is a major issue. PMID- 27255374 TI - Salvianolic Acid B Ameliorates Cerebral Ischemia/Reperfusion Injury Through Inhibiting TLR4/MyD88 Signaling Pathway. AB - Ischemic stroke can activate multiple transcription factors and cause inflammatory reactions, which involve pattern recognition receptors with immunostimulatory effects. Toll-like receptor 4 (TLR4) is one of the receptors related to innate immunity and several inflammatory reactions. The promising anti inflammatory activity of salvianolic acid B (SAB) had been previously reported, but its effect on ischemic stroke remains unknown. An oxygen-glucose deprivation and reoxygenation (OGD/R) model in vitro and a middle cerebral artery occlusion (MCAO) model in vivo were used in this paper, and the results showned that SAB remarkably increased the viabilities of PC12 cells and primary cortical neurons after OGD/R injury and notably prevented cerebral ischemia/reperfusion (I/R) injury. SAB also significantly ameliorated NeuN release from primary cortical neurons. Further research indicated that the neuroprotection of SAB was completed through inhibiting the TLR4/MyD88/TRAF6 signaling pathway. The blocking of TLR4 by SAB also restrained NF-kB transcriptional activity and pro-inflammatory cytokine responses (IL-1beta, IL-6, and TNF-alpha). These findings supply a new insight that will aid in clarifying the effect of SAB against cerebral I/R injury and provide the development of SAB as a potential candidate for treating ischemic stroke. PMID- 27255375 TI - Formulation and evaluation of proniosomes containing lornoxicam. AB - Proniosomes are the new generation provesicular drug delivery system of non-ionic surfactant, lecithin and cholesterol which upon reconstitution get converted into niosomes. The objective of current study was to develop stable and sustain transdermal delivery system for lornoxicam. Lornoxicam-loaded topically applied proniosomal gel was formulated, optimized, and evaluated with the aim to deliver drug transdermally. Lornoxicam-loaded proniosomal gels were prepared that contained Lutrol F68 and lecithin as surfactants, cholesterol as a stabilizer, and minimal amount of ethanol and trace water. The resultant lornoxicam-loaded proniosomal gel were assessed for stability and the proniosomes-derived niosomes were characterized for morphology, size, zeta potential, and entrapment efficiency, which revealed that they were suitable for skin application. The coacervation phase separation technique was used in formulation of lornoxicam proniosomal gel and the gel was further assessed for in vitro permeation of lornoxicam through the freshly excised rat skin and the cumulative permeation amount of lornoxicam from proniosome, all exhibited significant increase as compared to 1.0 % lornoxicam-loaded pure gel. The optimized F5 batch had shown maximum entrapment efficiency up to 66.98 %. It has shown sustained drug release for more than 24 h. The skin permeability of proniosomal gel was found to be 59.73 %. The SEM and zeta potential studies showed formation of good and stable vesicles. Thus, proniosomes proved to have better potential for transdermal delivery of lornoxicam over conventional gel formulations. PMID- 27255376 TI - Immunogenetic markers associated with a naturally acquired humoral immune response against an N-terminal antigen of Plasmodium vivax merozoite surface protein 1 (PvMSP-1). AB - BACKGROUND: Humoral immune responses against proteins of asexual blood-stage malaria parasites have been associated with clinical immunity. However, variations in the antibody-driven responses may be associated with a genetic component of the human host. The objective of the present study was to evaluate the influence of co-stimulatory molecule gene polymorphisms of the immune system on the magnitude of the humoral immune response against a Plasmodium vivax vaccine candidate antigen. METHODS: Polymorphisms in the CD28, CTLA4, ICOS, CD40, CD86 and BLYS genes of 178 subjects infected with P. vivax in an endemic area of the Brazilian Amazon were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The levels of IgM, total IgG and IgG subclasses specific for ICB2-5, i.e., the N-terminal portion of P. vivax merozoite surface protein 1 (PvMSP-1), were determined by enzyme-linked immuno assay. The associations between the polymorphisms and the antibody response were assessed by means of logistic regression models. RESULTS: After correcting for multiple testing, the IgG1 levels were significantly higher in individuals recessive for the single nucleotide polymorphism rs3116496 in CD28 (p = 0.00004). Furthermore, the interaction between CD28 rs35593994 and BLYS rs9514828 had an influence on the IgM levels (p = 0.0009). CONCLUSIONS: The results of the present study support the hypothesis that polymorphisms in the genes of co-stimulatory components of the immune system can contribute to a natural antibody-driven response against P. vivax antigens. PMID- 27255378 TI - Effects of platelet-rich plasma on liver regeneration in CCl4-induced hepatotoxicity model. AB - Numerous bioactive growth factors and cytokines in platelet-rich plasma (PRP) have recently made it an attractive biomaterial for therapeutic purposes. These growth factors have the potential to regenerate the injured tissues. The aim of this study was to investigate the therapeutic effects of PRP in hepatotoxic animal model. Hepatotoxicity was induced in rats by oral administration of 4 mL/kg/week of CCl4 diluted 1:1 in corn oil for 10 weeks. To confirm the hepatotoxicity, 24 h after the last CCl4 administration, blood samples were collected via cardiac puncture to assess the serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein, and total bilirubin. Twenty-four hours after blood collection, the experimental animals received a single injection of PRP (1 mL) via the anterior mesenteric vein. One week later, all biochemical tests were performed again, and the rats were scarified and their livers were removed, prepared histologically, and stained. The stereological analyses were performed to evaluate the effects of PRP on histopathological features of CCl4-treated livers. The results were compared statistically with the corresponding control and CCl4+normal saline (NS) treated animals. A significant decrease in the number and volume of hepatocytes (p = 0.01), and also a reduction in the volume of sinusoids (p = 0.001) and connective tissue (p = 0.04), were observed in the PRP-treated animals compared with the CCl4+NS-treated ones. Our findings demonstrated that application of PRP had beneficial effects on CCl4-induced fibrosis; however, it had detrimental effects on the total number of hepatocytes and the volume of hepatocytes and sinusoidal spaces. PMID- 27255377 TI - The level of netrin-1 is decreased in newly diagnosed type 2 diabetes mellitus patients. AB - BACKGROUND: Pancreatic beta-cell dysfunction resulting from inflammation has been recognized to contribute to type 2 diabetes mellitus (T2DM). Netrin-1 is a new indicator of subclinical inflammation and it has a role in beta-cell apoptosis. This study evaluated the level of netrin-1 in newly diagnosed T2DM patients and explored whether netrin-1 is a reliable marker or a key factor in the development of T2DM. METHODS: Netrin-1 level was determined using a commercially available human enzyme-linked immune sorbent assay (ELISA) kit. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index to measure insulin resistance. The sample consisted of 30 patients with newly diagnosed T2DM who had a glycosylated hemoglobin (HbA1c) level ranging from 7.5 % (58 mmol/mol) to 10.5 % (91 mmol/mol). The control group consisted of 26 healthy individuals matched for age and body mass index. RESULTS: The netrin-1 level of T2DM patients was significantly lower than that of healthy controls (p < 0.01). Logistic regression analysis showed that the level of netrin-1 was negatively correlated with HOMA-IR, fasting blood glucose, postprandial blood glucose, fasting insulin and HbA1c. CONCLUSIONS: Plasma netrin-1 levels were decreased in patients with newly diagnosed T2DM, and the levels of netrin-1 were negatively associated with IR and glucose homeostasis. Future studies on the precise mechanism will offer new insights into the prevention and treatment of T2DM. PMID- 27255380 TI - Pyrazinamide Induced Rat Cholestatic Liver Injury through Inhibition of FXR Regulatory Effect on Bile Acid Synthesis and Transport. AB - Pyrazinamide (PZA) is an indispensable first-line drug used for the treatment of tuberculosis which may cause serious hepatotoxicity; however, the mechanisms underlying these toxicities are poorly understood. Cholestasis plays an important role in drug-induced liver injury. Since there were no previous published works reported cholestasis and PZA hepatotoxicity relationship, this study aimed to identify whether PZA can induce liver injury with characterized evidences of cholestasis and to clarify expression changes of proteins related to both bile acid synthesis and transport in PZA-induced liver injury. PZA (2 g/kg) was administered for 7 consecutive days by oral gavage. Results showed there were 2 fold elevation in both ALT and AST serum levels in PZA-treated rats. In addition, a 10-fold increment in serum total bile acid was observed after PZA administration. The mRNA and protein expressions of bile acid synthesis and transport parameters were markedly altered, in which FXR, Bsep, Mrp2, Mdr2, Ostalpha/beta, Oatp1a1, Oatp1b2, and Cyp8b1 were decreased (P < .05), while Mrp3, Ntcp, Oatp1a4, and Cyp7a1 were increased (P < .05). Moreover, treatment with the FXR agonist obeticholic acid (OCA) generated obvious reductions in serum ALT, AST, and TBA levels in PZA-treated rats. Those effects were due to transcriptional regulation of pre-mentioned target genes by OCA. Taken together, these results suggested that PZA-induced cholestatic liver injury was related to FXR inhibition, leading to the dysfunction in bile acid synthesis and transport. PMID- 27255379 TI - Statistical inference of a convergent antibody repertoire response to influenza vaccine. AB - BACKGROUND: Vaccines dramatically affect an individual's adaptive immune system and thus provide an excellent means to study human immunity. Upon vaccination, the B cells that express antibodies (Abs) that happen to bind the vaccine are stimulated to proliferate and undergo mutagenesis at their Ab locus. This process may alter the composition of B cell lineages within an individual, which are known collectively as the antibody repertoire (AbR). Antibodies are also highly expressed in whole blood, potentially enabling RNA sequencing (RNA-seq) technologies to query this diversity. Less is known about the diversity of AbR responses across individuals to a given vaccine and if individuals tend to yield a similar response to the same antigenic stimulus. METHODS: Here we implement a bioinformatic pipeline that extracts the AbR information from a time-series RNA seq dataset of five patients who were administered a seasonal trivalent influenza vaccine (TIV). We harness the detailed time-series nature of this dataset and use methods based in functional data analysis (FDA) to identify the Abs that respond to the vaccine. We then design and implement rigorous statistical tests in order to ask whether or not these patients exhibit a convergent AbR response to the same TIV. RESULTS: We find that high-resolution time-series data can be used to help identify the Abs that respond to an antigenic stimulus and that this response can exhibit a convergent nature across patients inoculated with the same vaccine. However, correlations in AbR diversity among individuals prior to inoculation can confound inference of a convergent signal unless it is taken into account. CONCLUSIONS: We developed a framework to identify the elements of an AbR that respond to an antigen. This information could be used to understand the diversity of different immune responses in different individuals, as well as to gauge the effectiveness of the immune response to a given stimulus within an individual. We also present a framework for testing a convergent hypothesis between AbRs; a hypothesis that is more difficult to test than previously appreciated. Our discovery of a convergent signal suggests that similar epitopes do select for antibodies with similar sequence characteristics. PMID- 27255382 TI - Editor's Highlight: Abrasion of Artificial Stones as a New Cause of an Ancient Disease. Physicochemical Features and Cellular Responses. AB - New outbursts of silicosis were recently reported among workers manufacturing an engineered material known as "artificial stone," composed by high percentages of quartz (up to 98%) agglomerated with pigments and polymeric resins. Dusts released by abrasion during artificial stone polishing were characterized for particle size, morphology, and elemental composition and studied for (1) ability to catalyze free radical generation in acellular tests, (2) membranolytic potential on human erythrocytes, (3) cytotoxic activity (lactate dehydrogenase release) on murine alveolar macrophages (MH-S) and human bronchial epithelial (BEAS-2B) cell lines, (4) induction of epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Min-U-Sil 5 was used as reference quartz. Artificial stone dusts exhibited morphological features close to quartz, but contained larger amount of metal transition ions (mainly, Fe, Cu, and Ti), potentially responsible for the high reactivity in free radical generation observed. Opposite to Min-U-Sil 5, they were neither hemolytic nor cytotoxic on MH-S cells, a low cytotoxicity only being observed with BEAS-2B cells. The presence on the particle surface of residues of the resin accounts for this attenuated behavior, as hemolysis appeared and cytotoxicity increased after thermal degradation of the resin, when the free quartz surface was exposed. All dusts induced EMT with loss of E cadherin expression and increased the expression of mesenchymal proteins (alpha smooth muscle actin and vimentin). This may contribute to explain the development of fibrosis on workers exposed to artificial stone dusts. PMID- 27255381 TI - Mechanisms of Doxorubicin Toxicity in Pancreatic beta-Cells. AB - Exposure to chemotherapeutic agents has been linked to an increased risk of type 2 diabetes (T2D), a disease characterized by both the peripheral insulin resistance and impaired glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells. Using the rat beta-cell line INS-1 832/13 and isolated mouse pancreatic islets, we investigated the effect of the chemotherapeutic drug doxorubicin (Adriamycin) on pancreatic beta-cell survival and function. Exposure of INS-1 832/13 cells to doxorubicin caused impairment of GSIS, cellular viability, an increase in cellular toxicity, as soon as 6 h post-exposure. Doxorubicin impaired plasma membrane electron transport (PMET), a pathway dependent on reduced equivalents NADH and NADPH, but failed to redox cycle in INS 1 832/13 cells and with their lysates. Although NADPH/NADP(+ )content was unaffected, NADH/NAD(+ )content decreased at 4 h post-exposure to doxorubicin, and was followed by a reduction in ATP content. Previous studies have demonstrated that doxorubicin functions as a topoisomerase II inhibitor via induction of DNA cross-linking, resulting in apoptosis. Doxorubicin induced the expression of mRNA for mdm2, cyclin G1, and fas whereas downregulating p53, and increased the melting temperature of genomic DNA, consistent with DNA damage and induction of apoptosis. Doxorubicin also induced caspase-3 and -7 activity in INS 1 832/13 cells and mouse islets; co-treatment with the pan-caspase inhibitor Z VAD-FMK temporarily attenuated the doxorubicin-mediated loss of viability in INS 1 832/13 cells. Together, these data suggest that DNA damage, not H2O2 produced via redox cycling, is a major mechanism of doxorubicin toxicity in pancreatic beta-cells. PMID- 27255383 TI - Histone Deacetylase Inhibitors Prolong Cardiac Repolarization through Transcriptional Mechanisms. AB - Histone deacetylase (HDAC) inhibitors are an emerging class of anticancer agents that modify gene expression by altering the acetylation status of lysine residues of histone proteins, thereby inducing transcription, cell cycle arrest, differentiation, and cell death or apoptosis of cancer cells. In the clinical setting, treatment with HDAC inhibitors has been associated with delayed cardiac repolarization and in rare instances a lethal ventricular tachyarrhythmia known as torsades de pointes. The mechanism(s) of HDAC inhibitor-induced effects on cardiac repolarization is unknown. We demonstrate that administration of structurally diverse HDAC inhibitors to dogs causes delayed but persistent increases in the heart rate corrected QT interval (QTc), an in vivo measure of cardiac repolarization, at timepoints far removed from the Tmax for parent drug and metabolites. Transcriptional profiling of ventricular myocardium from dogs treated with various HDAC inhibitors demonstrated effects on genes involved in protein trafficking, scaffolding and insertion of various ion channels into the cell membrane as well as genes for specific ion channel subunits involved in cardiac repolarization. Extensive in vitro ion channel profiling of various structural classes of HDAC inhibitors (and their major metabolites) by binding and acute patch clamp assays failed to show any consistent correlations with direct ion channel blockade. Drug-induced rescue of an intracellular trafficking deficient mutant potassium ion channel, hERG (G601S), and decreased maturation (glycosylation) of wild-type hERG expressed by CHO cells in vitro correlated with prolongation of QTc intervals observed in vivo The results suggest that HDAC inhibitor-induced prolongation of cardiac repolarization may be mediated in part by transcriptional changes of genes required for ion channel trafficking and localization to the sarcolemma. These data have broad implications for the development of these drug classes and suggest that the optimal time to assess potentially transcriptionally mediated physiologic effects will be delayed relative to an epigenetic drug's Tmax/Cmax. PMID- 27255384 TI - From the Cover: Disease-Induced Disparities in Formation of the Nanoparticle Biocorona and the Toxicological Consequences. AB - Nanoparticle (NP) association with macromolecules in a physiological environment forms a biocorona (BC), which alters NP distribution, activity, and toxicity. While BC formation is dependent on NP physicochemical properties, little information exists on the influence of the physiological environment. Obese individuals and those with cardiovascular disease exist with altered serum chemistry, which is expected to influence BC formation and NP toxicity. We hypothesize that a BC formed on NPs following incubation in hyperlipidemic serum will result in altered NP-BC protein content, cellular association, and toxicity compared to normal serum conditions. We utilized Fe3O4 NPs, which are being developed as MRI contrast and tumor targeting agents to test our hypothesis. We used rat aortic endothelial cells (RAECs) within a dynamic flow in vitro exposure system to more accurately depict the in vivo environment. A BC was formed on 20nm PVP-suspended Fe3O4 NPs following incubation in water, 10% normal or hyperlipidemic rat serum. Addition of BCs resulted in increased hydrodynamic size and decreased surface charge. More cholesterol associated with Fe3O4 NPs after incubation in hyperlipidemic as compared with normal serum. Using quantitative proteomics, we identified unique differences in BC protein components between the 2 serum types. Under flow conditions, formation of a BC from both serum types reduced RAECs association of Fe3O4 NPs. Addition of BCs was found to exacerbate RAECs inflammatory gene responses to Fe3O4 NPs (Fe3O4-hyperlipidemic > Fe3O4 normal > Fe3O4) including increased expression of IL-6, TNF-alpha, Cxcl-2, VCAM 1, and ICAM-1. Overall, these findings demonstrate that disease-induced variations in physiological environments have a significant impact NP-BC formation, cellular association, and cell response. PMID- 27255385 TI - Generalized Concentration Addition Modeling Predicts Mixture Effects of Environmental PPARgamma Agonists. AB - The vast array of potential environmental toxicant combinations necessitates the development of efficient strategies for predicting toxic effects of mixtures. Current practices emphasize the use of concentration addition to predict joint effects of endocrine disrupting chemicals in coexposures. Generalized concentration addition (GCA) is one such method for predicting joint effects of coexposures to chemicals and has the advantage of allowing for mixture components to have differences in efficacy (ie, dose-response curve maxima). Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that plays a central role in regulating lipid homeostasis, insulin sensitivity, and bone quality and is the target of an increasing number of environmental toxicants. Here, we tested the applicability of GCA in predicting mixture effects of therapeutic (rosiglitazone and nonthiazolidinedione partial agonist) and environmental PPARgamma ligands (phthalate compounds identified using EPA's ToxCast database). Transcriptional activation of human PPARgamma1 by individual compounds and mixtures was assessed using a peroxisome proliferator response element-driven luciferase reporter. Using individual dose-response parameters and GCA, we generated predictions of PPARgamma activation by the mixtures, and we compared these predictions with the empirical data. At high concentrations, GCA provided a better estimation of the experimental response compared with 3 alternative models: toxic equivalency factor, effect summation and independent action. These alternatives provided reasonable fits to the data at low concentrations in this system. These experiments support the implementation of GCA in mixtures analysis with endocrine disrupting compounds and establish PPARgamma as an important target for further studies of chemical mixtures. PMID- 27255386 TI - From the Cover: Thirdhand Cigarette Smoke Causes Stress-Induced Mitochondrial Hyperfusion and Alters the Transcriptional Profile of Stem Cells. AB - Thirdhand cigarette smoke (THS) was recently recognized as an environmental health hazard; however, little is known about it effects on cells. Mitochondria are sensitive monitors of cell health and report on environmentally induced stress. We tested the effects of low levels of THS extracted from terry cloth on mitochondrial morphology and function using stem cells with well-defined mitochondria. Concentrations of THS that did not kill cells caused stress-induced mitochondrial hyperfusion (SIMH), which was characterized by changes in mitochondrial morphology indicative of fusion, increased mitochondrial membrane potential (MMP), increased ATP levels, increased superoxide production, and increased oxidation of mitochondrial proteins. SIMH was accompanied by a decrease in Fis1 expression, a gene responsible for mitochondrial fission, and a decrease in apoptosis-related genes, including Aifm2, Bbc3, and Bid There was also down regulation of Ucp2, Ucp4, and Ucp5, genes that decrease MMP thereby reducing oxidative phosphorylation, while promoting glycolysis. These effects, which collectively accompany SIMH, are a prosurvival mechanism to rescue damaged mitochondria and protect cells from apoptosis. Prolonged exposure to THS caused a reduction in MMP and decreased cell proliferation, which likely leads to apoptosis. PMID- 27255387 TI - Editor's Highlight: Characterization of Hepatotoxicity Mechanisms Triggered by Designer Cathinone Drugs (beta-Keto Amphetamines). AB - The use of cathinone designer drugs in recreational settings has been associated with severe toxic effects, including liver damage. The precise mechanisms by which cathinones induce hepatotoxicity and whether they act by common pathways remain to be elucidated. Herein, we assessed the toxicity of the cathinones methylone, pentedrone, 3,4-methylenedioxypyrovalerone (MDPV) and 4 methylethcathinone (4-MEC) in primary rat hepatocytes (PRH) and HepaRG cells, and compared with that of 3,4-methylenedioxymethamphetamine (MDMA). MDPV and pentedrone were significantly more toxic than MDMA, while methylone was the least cytotoxic compound. Importantly, PRH revealed to be the most sensitive experimental model and was thus used to explore the mechanisms underlying the observed toxicity. All drugs elicited the formation of reactive oxygen and nitrogen species (ROS and RNS), but more markedly for methylone, pentedrone and 4 MEC. GSH depletion was also a common effect at the highest concentration tested, whereas only MDPV and pentedrone caused a significant decrease in ATP levels. The antioxidants ascorbic acid or N-acetyl-L-cysteine partially attenuated the observed cell death. All cathinones triggered significant caspase activation and apoptosis, which was partially reversed by the caspase inhibitor Ac-LETD-CHO. In conclusion, the present data shows that (1) cathinones induce in vitro hepatotoxic effects that vary in magnitude among the different analogues, (2) oxidative stress and mitochondrial dysfunction play a role in cathinones-induced hepatic injury, and (3) apoptosis appears to be an important pathway of cell death elicited by these novel drugs. PMID- 27255388 TI - Deducing the symmetry of helical assemblies: Applications to membrane proteins. AB - Helical reconstruction represents a convenient and powerful approach for structure determination of macromolecules that assemble into helical arrays. In the case of membrane proteins, formation of tubular crystals with helical symmetry represents an attractive alternative, especially when their small size precludes the use of single-particle analysis. An essential first step for helical reconstruction is to characterize the helical symmetry. This process is often daunting, due to the complexity of helical diffraction and to the low signal-to-noise ratio in images of individual assemblies. Furthermore, the large diameters of the tubular crystals produced by membrane proteins exacerbates the innate ambiguities that, if not resolved, will produce incorrect structures. In this report, we describe a set of tools that can be used to eliminate ambiguities and to validate the choice of symmetry. The first approach increases the signal to-noise ratio along layer lines by incoherently summing data from multiple helical assemblies, thus producing several candidate indexing schemes. The second approach compares the layer lines from images with those from synthetic models built with the various candidate schemes. The third approach uses unit cell dimensions measured from collapsed tubes to distinguish between these candidate schemes. These approaches are illustrated with tubular crystals from a boron transporter from yeast, Bor1p, and a beta-barrel channel from the outer membrane of E. coli, OmpF. PMID- 27255389 TI - The Gut Microbiome and Obesity. AB - The gut microbiome consists of trillions of bacteria which play an important role in human metabolism. Animal and human studies have implicated distortion of the normal microbial balance in obesity and metabolic syndrome. Bacteria causing weight gain are thought to induce the expression of genes related to lipid and carbohydrate metabolism thereby leading to greater energy harvest from the diet. There is a large body of evidence demonstrating that alteration in the proportion of Bacteroidetes and Firmicutes leads to the development of obesity, but this has been recently challenged. It is likely that the influence of gut microbiome on obesity is much more complex than simply an imbalance in the proportion of these phyla of bacteria. Modulation of the gut microbiome through diet, pre- and probiotics, antibiotics, surgery, and fecal transplantation has the potential to majorly impact the obesity epidemic. PMID- 27255390 TI - Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study. AB - Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits, but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age matched cirrhotic patients without MHE; the resting motor threshold, the short interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE. PMID- 27255391 TI - Expression and actions of GnIH and its orthologs in vertebrates: Current status and advanced knowledge. AB - The physiology of reproduction is very complex and is regulated by multiple factors, including a number of hypothalamic neuropeptides. In last few decades, various neuropeptides have been discovered to be involved in stimulation or inhibition of reproduction. In 2000, Tsutsui and colleagues uncovered gonadotropin-inhibitory hormone (GnIH), a neuropeptide generating inhibitory drive to the reproductive axis, in the brain of Coturnix quail. Afterward, GnIH orthologs were discovered in other vertebrates from fish to mammals including human. In these vertebrates, all the discovered GnIH and its ortholgs have LPXRFamide (X=L or Q) sequence at C-terminus. GnIH orthologs of mammals and primates are also termed as RFamide-related peptide (RFRP)-1 and -3 that too have an LPXRFamide (X=L or Q) motif at their C-terminus. GnIH and its orthologs form a member of the RFamide peptide family. GnIH signals via its canonical G protein coupled receptor 147 (GPR147). Both GnIH and GPR147 are expressed in hypothalamus and other brain regions. Besides actions through the hypothalamic GnRH and kisspeptinergic neurons, GnIH-GPR147 signaling exerts inhibitory effect on the reproductive axis via pituitary gonadotropes and directly at gonadal level. Various factors including availability and quality of food, photoperiod, temperature, social interaction, various stresses and some diseases modulate GnIH GPR147 signaling. In this review, we have discussed expression and actions of GnIH and its orthologs in vertebrates. Special emphasis is given on the role of GnIH-GPR147 signaling pathway in the regulation of reproduction. We have also reviewed and discussed currently available literature on the participation of GnIH-GPR147 signaling pathway in the stress modulation of reproduction. PMID- 27255392 TI - Compressed sodium chloride as a fast-acting antimicrobial surface: results of a pilot study. AB - Antimicrobial surfaces are currently being studied as an aid to reduce transmission of pathogens leading to healthcare-associated infections (HAIs). Among the most harmful and costly pathogens that cause HAIs is meticillin resistant Staphylococcus aureus (MRSA). Currently available and previously investigated antimicrobial surface technologies that are effective against MRSA (e.g. copper alloy surfaces) take 30min to several hours to achieve significant reduction. This article presents a new antimicrobial surface technology made of compressed sodium chloride that reduces MRSA 20-30 times faster than copper alloy surfaces. PMID- 27255394 TI - Research misconduct and data fraud in clinical trials. PMID- 27255395 TI - Prevalence of data fraud. PMID- 27255393 TI - Risk factors of early recurrence within 6 months after esophagectomy following neoadjuvant chemotherapy for resectable advanced esophageal squamous cell carcinoma. AB - BACKGROUND: Esophagectomy following neoadjuvant chemotherapy (NAC) is a standard treatment for resectable advanced esophageal cancer in Japan. However, approximately 10 % of patients with resectable advanced esophageal cancer experience recurrence within 6 months. METHODS: One hundred twenty-eight patients with resectable advanced esophageal cancer underwent NAC between October 2008 and July 2015 in Kumamoto University Hospital. Among them, 82 patients with esophageal squamous cell carcinoma (SCC), who underwent curative esophagectomy without adjuvant treatment, were eligible. Clinicopathological factors correlated with early recurrence were retrospectively analyzed. RESULTS: Of 82 patients, 14 (17 %) recurred within 6 months after surgery. The logistic regression analysis suggested that CRP before NAC >= 0.5 mg/dl [hazard ratio (HR) 33.8, 95 % confidence interval (CI) 2.767-413.9; p = 0.006), presence of poorly differentiated SCC component (HR 138, 95 % CI 5.339-3576; p = 0.003), and pathological vessel invasion (HR 16.3, 95 % CI 1.960-136.1; p = 0.010) were candidates for independent risk factors of early recurrence. Patients with at least two factors frequently recurred (82 %). Of 14 patients with early recurrence, 13 (93 %) had a distant metastasis. CONCLUSIONS: Patients with resectable advanced esophageal cancer with at least two factors of CRP before NAC >= 0.5 mg/dl, presence of poorly differentiated SCC component, and pathological vessel invasion might be at high risk for early recurrence after esophagectomy following NAC. These patients might be considered for additional treatment and should be meticulously followed up after treatment. PMID- 27255396 TI - Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients. AB - OBJECTIVES: To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. METHODS: Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. RESULTS: Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. CONCLUSION: Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. KEY POINTS: * Xp11.2/TFE RCC was more prevalent in young women. * On unenhanced CT, Xp11.2/TFE RCC attenuation was greater than in renal parenchyma. * Xp111/2TFE RCC arises primarily from the renal medulla. * Xp11.2/TFE RCC enhancement was less than in the cortex on all phases. * Enhancement was greater than in the medulla in arterial and corticomedullary phase. PMID- 27255397 TI - Outcome of hypovascular hepatic nodules with positive uptake of gadoxetic acid in patients with cirrhosis. AB - OBJECTIVES: To evaluate the longitudinal risk to patients with cirrhosis of hypervascular hepatocellular carcinoma (HCC) developing from hypovascular hepatic nodules that show positive uptake of gadoxetic acid (hyperintensity) on hepatocyte phase images. METHODS: In 69 patients, we evaluated findings from serial follow-up examinations of 633 hepatic nodules that appeared hypovascular and hyperintense on initial gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) until the nodules demonstrated hypervascularity and were diagnosed as hypervascular HCC. Cox analyses were performed to identify risk factors for the development of hypervascular HCCs from the nodules. RESULTS: The median follow-up was 663 days (range, 110 to 1215 days). Hypervascular HCCs developed in six of the 633 nodules (0.9 %) in five of the 69 patients. The only independent risk factor, the nodule's initial maximum diameter of 10 mm or larger, demonstrated a hazard ratio of 1.25. The one-year risk of hypervascular HCC developing from a nodule was 0.44 %. The risk was significantly higher for nodules of larger diameter (1.31 %) than those smaller than 10 mm (0.10 %, p < 0.01). CONCLUSIONS: Hypervascular HCC rarely develops from hypovascular, hyperintense hepatic nodules. We observed low risk even for nodules of 10 mm and larger diameter at initial examination. KEY POINTS: * Hypervascularization was rare on follow-up examination of hypovascular, hyperintense nodules * The risk of hypervascularization in a nodule increased with large size * Hypovascular, hyperintense nodules require neither treatment nor more intense follow-up. PMID- 27255398 TI - Ultrasound assessment of the posterior circumflex humeral artery in elite volleyball players: Aneurysm prevalence, anatomy, branching pattern and vessel characteristics. AB - OBJECTIVES: To determine the prevalence of posterior circumflex humeral artery (PCHA) aneurysms and vessel characteristics of the PCHA and deep brachial artery (DBA) in elite volleyball players. METHODS: Two-hundred and eighty players underwent standardized ultrasound assessment of the dominant arm by a vascular technologist. Assessment included determination of PCHA aneurysms (defined as segmental vessel dilatation >=150 %), PCHA and DBA anatomy, branching pattern, vessel course and diameter. RESULTS: The PCHA and DBA were identified in 100 % and 93 % (260/280) of cases, respectively. The prevalence of PCHA aneurysms was 4.6 % (13/280). All aneurysms were detected in proximal PCHA originating from the axillary artery (AA). The PCHA originated from the AA in 81 % of cases (228/280), and showed a curved course dorsally towards the humeral head in 93 % (211/228). The DBA originated from the AA in 73 % of cases (190/260), and showed a straight course parallel to the AA in 93 % (177/190). CONCLUSIONS: PCHA aneurysm prevalence in elite volleyball players is high and associated with a specific branching type: a PCHA that originates from the axillary artery. Radiologists should have a high index of suspicion for this vascular overuse injury. For the first time vessel characteristics and reference values are described to facilitate ultrasound assessment. KEY POINTS: * Prevalence of PCHA aneurysms is 4.6 % among elite volleyball players. * All aneurysms are in proximal PCHA that originates directly from AA. * Vessel characteristics and reference values are described to facilitate US assessment. * Mean PCHA and DBA diameters can be used as reference values. * Radiologists need a high index of suspicion for this vascular overuse injury. PMID- 27255400 TI - Prediction of infarction development after endovascular stroke therapy with dual energy computed tomography. AB - OBJECTIVES: After intraarterial recanalisation (IAR), the haemorrhage and the blood-brain barrier (BBB) disruption can be distinguished using dual-energy computed tomography (DECT). The aim of the present study was to investigate whether future infarction development can be predicted from DECT. METHODS: DECT scans of 20 patients showing 45 BBB disrupted areas after IAR were assessed and compared with follow-up examinations. Receiver operator characteristic (ROC) analyses using densities from the iodine map (IM) and virtual non-contrast (VNC) were performed. RESULTS: Future infarction areas are denser than future non infarction areas on IM series (23.44 +/- 24.86 vs. 5.77 +/- 2.77; p < 0.0001) and more hypodense on VNC series (29.71 +/- 3.33 vs. 35.33 +/- 3.50; p < 0.0001). ROC analyses for the IM series showed an area under the curve (AUC) of 0.99 (cut-off: <9.97 HU; p < 0.05; sensitivity 91.18 %; specificity 100.00 %; accuracy 0.93) for the prediction of future infarctions. The AUC for the prediction of haemorrhagic infarctions was 0.78 (cut-off >17.13 HU; p < 0.05; sensitivity 90.00 %; specificity 62.86 %; accuracy 0.69). The VNC series allowed prediction of infarction volume. CONCLUSIONS: Future infarction development after IAR can be reliably predicted with the IM series. The prediction of haemorrhages and of infarction size is less reliable. KEY POINTS: * The IM series (DECT) can predict future infarction development after IAR. * Later haemorrhages can be predicted using the IM and the BW series. * The volume of definable hypodense areas in VNC correlates with infarction volume. PMID- 27255399 TI - Subsolid pulmonary nodule morphology and associated patient characteristics in a routine clinical population. AB - OBJECTIVES: To determine the presence and morphology of subsolid pulmonary nodules (SSNs) in a non-screening setting and relate them to clinical and patient characteristics. METHODS: A total of 16,890 reports of clinically obtained chest CT (06/2011 to 11/2014, single-centre) were searched describing an SSN. Subjects with a visually confirmed SSN and at least two thin-slice CTs were included. Nodule volumes were measured. Progression was defined as volume increase exceeding the software interscan variation. Nodule morphology, location, and patient characteristics were evaluated. RESULTS: Fifteen transient and 74 persistent SSNs were included (median follow-up 19.6 [8.3-36.8] months). Subjects with an SSN were slightly older than those without (62 vs. 58 years; p = 0.01), but no gender predilection was found. SSNs were mostly located in the upper lobes. Women showed significantly more often persistent lesions than men (94 % vs. 69 %; p = 0.002). Part-solid lesions were larger (1638 vs. 383 mm3; p < 0.001) and more often progressive (68 % vs. 38 %; p = 0.02), compared to pure ground-glass nodules. Progressive SSNs were rare under the age of 50 years. Logistic regression analysis did not identify additional nodule parameters of future progression, apart from part-solid nature. CONCLUSIONS: This study confirms previously reported characteristics of SSNs and associated factors in a European, routine clinical population. KEY POINTS: * SSNs in women are significantly more often persistent compared to men. * SSN persistence is not associated with age or prior malignancy. * The majority of (persistent) SSNs are located in the upper lung lobes. * A part-solid nature is associated with future nodule growth. * Progressive solitary SSNs are rare under the age of 50 years. PMID- 27255401 TI - Prediction of the treatment outcome using intravoxel incoherent motion and diffusional kurtosis imaging in nasal or sinonasal squamous cell carcinoma patients. AB - OBJECTIVES: To evaluate the diagnostic value of intravoxel incoherent motion (IVIM) and diffusional kurtosis imaging (DKI) parameters in nasal or sinonasal squamous cell carcinoma (SCC) patients to determine local control/failure. METHODS: Twenty-eight patients were evaluated. MR acquisition used single-shot spin-echo EPI with 12 b-values. Quantitative parameters (mean value, 25th, 50th and 75th percentiles) of IVIM (perfusion fraction f, pseudo-diffusion coefficient D*, and true-diffusion coefficient D), DKI (kurtosis value K, kurtosis corrected diffusion coefficient Dk) and apparent diffusion coefficient (ADC) were calculated. Parameter values at both the pretreatment and early-treatment period, and the percentage change between these two periods were obtained. RESULTS: Multivariate logistic regression analysis: the percentage changes of D (mean, 25th, 50th, 75th), K (mean, 50th, 75th), Dk (mean, 25th, 50th), and ADC (mean, 25th, 50th) were predictors of local control. ROC curve analysis: the parameter with the highest accuracy = the percentage change of D value with the histogram 25th percentile (0.93 diagnostic accuracy). Multivariate Cox regression analyses: the percentage changes of D (mean, 25th, 50th), K (mean, 50th, 75th), Dk (mean, 25th, 50th) and ADC (mean, 25th, 50th) are predictors. CONCLUSIONS: IVIM and DKI parameters, especially the D-value's histogram 25th percentile, are useful for predicting local control. KEY POINTS: * Noninvasive assessment of treatment outcome in SCC patients was achieved using IVIM/DKI. * Several IVIM and DKI parameters can predict the local control. * Especially, the D-value's histogram 25th percentile has high diagnostic accuracy. PMID- 27255402 TI - The number of unrecognized myocardial infarction scars detected at DE-MRI increases during a 5-year follow-up. AB - OBJECTIVES: In an elderly population, the prevalence of unrecognized myocardial infarction (UMI) scars found via late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging was more frequent than expected. This study investigated whether UMI scars detected with LGE-CMR at age 70 would be detectable at age 75 and whether the scar size changed over time. METHODS: From 248 participants that underwent LGE-CMR at age 70, 185 subjects underwent a follow-up scan at age 75. A myocardial infarction (MI) scar was defined as late enhancement involving the subendocardium. RESULTS: In the 185 subjects that underwent follow-up, 42 subjects had a UMI scar at age 70 and 61 subjects had a UMI scar at age 75. Thirty-seven (88 %) of the 42 UMI scars seen at age 70 were seen in the same myocardial segment at age 75. The size of UMI scars did not differ between age 70 and 75. CONCLUSIONS: The prevalence of UMI scars detected at LGE-CMR increases with age. During a 5-year follow-up, 88 % (37/42) of the UMI scars were visible in the same myocardial segment, reassuring that UMI scars are a consistent finding. The size of UMI scars detected during LGE-CMR did not change over time. KEY POINTS: * UMI scars detected by LGE-CMR are frequent in elderly. * The prevalence of UMI scars detected with LGE-CMR increases with age. * UMI scar size does not change over time. PMID- 27255403 TI - Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells. AB - During cancer metastasis, circulating tumor cells constantly experience hemodynamic shear stress in the circulation. Cellular responses to shear stress including cell viability and proliferation thus play critical roles in cancer metastasis. Here, we developed a microfluidic approach to establish a circulatory microenvironment and studied circulating human colon cancer HCT116 cells in response to a variety of magnitude of shear stress and circulating time. Our results showed that cell viability decreased with the increase of circulating time, but increased with the magnitude of wall shear stress. Proliferation of cells survived from circulation could be maintained when physiologically relevant wall shear stresses were applied. High wall shear stress (60.5 dyne/cm(2)), however, led to decreased cell proliferation at long circulating time (1 h). We further showed that the expression levels of beta-catenin and c-myc, proliferation regulators, were significantly enhanced by increasing wall shear stress. The presented study provides a new insight to the roles of circulatory shear stress in cellular responses of circulating tumor cells in a physiologically relevant model, and thus will be of interest for the study of cancer cell mechanosensing and cancer metastasis. PMID- 27255404 TI - Valproate-Associated Parkinsonism: A Critical Review of the Literature. AB - Valproate was first approved as an antiepileptic drug in 1962 and has since also become established as a mood stabiliser and as prophylaxis for migraine. In 1979, Lautin published the first description of a valproate-associated extrapyramidal syndrome. Many cases of valproate-associated parkinsonism have subsequently been published, but uncertainties remain concerning its prevalence, risk factors and prognosis. The aim of this paper is to provide a critical review of the existing literature on valproate-associated parkinsonism and to discuss possible mechanisms. Literature databases were searched systematically: we identified a total of 116 patients with valproate-associated parkinsonism published in case reports, case series and systematic analyses. Prevalence rates ranged widely, between 1.4 and 75 % of patients taking valproate. There was great heterogeneity with regard to clinical presentation, age of onset, valproate dose, concomitant conditions and imaging findings. In all patients apart from three, valproate plasma concentrations were within or even below the recommended reference range when the parkinsonism occurred. Parkinsonism was reversible in the majority of patients, although recovery was often prolonged and sometimes incomplete. A dopaminergic deficit was confirmed in three of six patients investigated with dopamine transporter imaging. Seven of 14 patients who were treated with dopaminergic medication had a good response. The quality of the evidence was assessed and probability of causation was examined using the Naranjo score, which ranged from 0 to 7 (median: 5.0). Several pathophysiological mechanisms, including altered gene expression and neurotransmitter signalling, enhanced neurodegeneration or unmasking subclinical dopaminergic degeneration, could theoretically lead to valproate-associated parkinsonism. Further studies are warranted to elucidate this entity and its underlying pathophysiology. PMID- 27255406 TI - Retrieving orbital angular momentum distribution of light with plasmonic vortex lens. AB - We utilize a plasmonic vortex lens (PVL) to retrieve the orbital angular momentum (OAM) distribution of light. The OAM modes are coupled to the surface plasmon polaritons (SPPs) in the form of various Bessel functions respectively. By decomposing the interference pattern of SPPs into these Bessel functions, we can retrieve the relative amplitude and the relative phase of input OAM modes simultaneously. Our scheme shows advantage in integration and can measure hybrid OAM states by one measurement. PMID- 27255405 TI - Barriers to the Use of Long-Acting Injectable Antipsychotics in the Management of Schizophrenia. AB - Schizophrenia and related disorders remain major disabling conditions, mainly due to antipsychotic treatment resistance and to relapses related to antipsychotic nonadherence. Treatment nonadherence rates are consistently high in long-term patients, but also in first-episode patients with schizophrenia. Long-acting injectable antipsychotics (LAIAs) were mainly developed to improve adherence to treatment and to reduce the rate of relapse and rehospitalization in schizophrenia due to treatment discontinuation. There is favorable clinical evidence, in terms of both efficacy and treatment adherence, that could support higher LAIA prescription rates, especially in patients in early phases of psychotic disorders. Several factors could be hindering wider use of LAIAs, mainly associated with perceptions and attitudes of patients, clinicians, and health managers or policy makers. The main aims of this review are (i) to summarize the existing data on the efficacy and tolerability of LAIAs compared with oral formulations in the management of schizophrenia and related disorders, focusing on the novel, second-generation LAIA options; (ii) to analyze the barriers that exist to the more widespread use of these formulations; and (iii) to discuss possible approaches to overcoming these barriers. PMID- 27255407 TI - [Randomised clinical trial to evaluate the efficacy and safety of a new pediculicide made with saponified olive oil in the eradication of Pediculus humanus capitis]. AB - INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of a new pediculicide in the eradication of Pediculus humanus capitis infestation. MATERIAL AND METHODS: A randomised clinical trial was designed, in which children aged between 5 and 15 years diagnosed with pediculosis were selected. Treatment was administered on days 1 and 7 after selection, and they were evaluated in 4 visits (day 2, 7, 9, and 14). The product under evaluation with saponified olive oil was Inex Pediculicide Soap(r), which was compared with Paranix(r), with a similar mechanism of action. The primary efficacy endpoint was the eradication of the parasite by day 14 (louse-free rate), using an intention to treat analysis. RESULTS: Six paediatricians from 5 Primary Health Care centres in the Community of Madrid (Spain) and one private clinic participated in the study. A total of 45 children were included, of which 75.6% were girls (n=34). The mean age was 7.1 years (95% CI 6.3-7.9). The large majority (80%) were middle class, and 82.2% had a history of previous pediculosis. The efficacy at 14 days was 76.2% (95% CI 52.8 91.8) in the group treated with Inex Pediculicide Soap(r) group, and 79.2% (95% CI 57.9-92.9) in Paranix(r) group (NNT=33.3). No adverse effects were observed with treatment. CONCLUSIONS: The 2 products were effective and safe in the eradication therapy Pediculus humanus capitis, with no statistical differences. PMID- 27255408 TI - Outcome of heavily pretreated recurrent oral squamous cell carcinoma after salvage resection: A monocentric retrospective analysis. AB - PURPOSE: The goals of the present study were to analyze survival data of patients who received salvage surgery due to recurrent oral squamous cell carcinoma (OSCC) of the oral cavity with curative intent, and to investigate the feasibility of microvascular flap reconstruction in a heavily pretreated patient cohort. MATERIAL AND METHODS: A total of 32 patients who received salvage surgery due to recurrent OSCC were included. The cohort was analyzed in regard to relevant clinical and pathological features. Survival was estimated by using Kaplan-Meier analysis and verified in a multivariate Cox regression model. RESULTS: All patients recovered well from surgery. The most common severe complication was free flap failure in 7 patients (24.1%). R0-resection was achieved in 16 patients (50%). Univariate Kaplan-Meier analysis showed that the estimated overall survival and disease-free survival of all patients after 24 months were 37.8% and 30.9%, respectively. Multivariate testing identified R1-resection was the only independent predictor of treatment failure. CONCLUSION: Salvage surgery is the only potential curative treatment option in recurrent OSCC. Microvascular reconstruction is feasible in heavily pretreated patients, but it is associated with a higher free flap failure rate. Recurrent OSCC in heavily pretreated patients shows different biological behavior. Further prospective clinical and molecular studies are needed to develop a better molecular understanding of recurrent OSCC and the best and safest individual therapeutic strategy. PMID- 27255410 TI - Engineering Paper-Based Sensors for Zika Virus. AB - The emergence of Zika virus (ZIKV) infections in Latin America and Southeast Asia has created an urgent need for new, simple, yet sensitive, diagnostic tests. We highlight recent work using paper-based sensors coupled with CRISPR/Cas9 to detect ZIKV RNA as a new approach to achieve rapid development and deployment of field-ready diagnostics for emerging infectious diseases. PMID- 27255409 TI - Identification of interleukin genes in Pogona vitticeps using a de novo transcriptome assembly from RNA-seq data. AB - Interleukins are a group of cytokines with complex immunomodulatory functions that are important for regulating immunity in vertebrate species. Reptiles and mammals last shared a common ancestor more than 350 million years ago, so it is not surprising that low sequence identity has prevented divergent interleukin genes from being identified in the central bearded dragon lizard, Pogona vitticeps, in its genome assembly. To determine the complete nucleotide sequences of key interleukin genes, we constructed full-length transcripts, using the Trinity platform, from short paired-end read RNA sequences from stimulated spleen cells. De novo transcript reconstruction and analysis allowed us to identify interleukin genes that are missing from the published P. vitticeps assembly. Identification of key cytokines in P. vitticeps will provide insight into the essential molecular mechanisms and evolution of interleukin gene families and allow for characterization of the immune response in a lizard for comparison with mammals. PMID- 27255411 TI - Dynamic CT myocardial perfusion imaging identifies early perfusion abnormalities in diabetes and hypertension: Insights from a multicenter registry. AB - BACKGROUND: To identify patients with early signs of myocardial perfusion reduction, a reference base for perfusion measures is needed. OBJECTIVE: To analyze perfusion parameters derived from dynamic computed tomography perfusion imaging (CTPI) in patients with suspected coronary artery disease (CAD), and relationship with risk factors. METHODS: In this multicenter study, coronary CT angiography (cCTA) and dynamic CTPI were performed by second-generation dual source CT in patients suspected of CAD. Risk factors were collected from hospital records. Patients with visual perfusion defects on CTPI, previous coronary intervention, or missing risk factor details were excluded. This analysis included 98 patients (mean age +/- standard deviation [SD], 59.0 +/- 8.6yrs; 73 male). Global measures of left ventricular myocardial blood flow (MBF), myocardial blood volume (MBV) and volume transfer constant (K(trans)) were calculated. RESULTS: Mean MBF was 139.3 +/- 31.4 mL/100 mL/min, MBV 19.1 +/- 2.7 mL/100 mL, and Ktrans 85.0 +/- 17.5 mL/100 mL/min. No significant differences in perfusion parameters were found by gender or age category. Hypertension and diabetes mellitus resulted in lower perfusion parameters (hypertension vs normotension: MBV 18.5 +/- 3.0 vs 19.7 +/- 2.3 mL/100 mL and K(trans) 82.0 +/- 18.0 vs 89.0 +/- 16.0, p < 0.05; diabetes vs no diabetes: MBF 128.5 +/- 31.5 vs 144.0 +/- 30.5 mL/100 mL/min and MBV 17.9 +/- 2.4 vs 19.4 +/- 2.8 mL/100 mL, p < 0.05). In patients with hyperlipidemia, MBF was higher (146.8 +/- 34.4 vs 130.7 +/- 24.3 mL/100 mL/min, p < 0.05). Smoking and family history did not show perfusion parameter differences. CONCLUSIONS: Dynamic CTPI identifies early perfusion disturbances in conditions like diabetes and hypertension. With further standardization, absolute perfusion measures may improve CAD risk stratification in patients without visual perfusion defects. PMID- 27255412 TI - Manifestations of Pediatric Intracranial Hypertension From the Intracranial Hypertension Registry. AB - OBJECTIVE: The purpose of this study was to examine the presenting symptoms, demographics, and interventions in pediatric patients enrolled in the Intracranial Hypertension Registry. METHODS: We analyzed confirmed intracranial hypertension patients <=18 years at the time of initial diagnosis who were enrolled in the registry. RESULTS: A total of 203 patients met the criteria for inclusion; 142 (70%) were considered primary intracranial hypertension. Females made up 72.5% (103 of 142) and 75.8% (47 of 61) in the primary intracranial hypertension and secondary intracranial hypertension groups, respectively. There were no clinically significant differences in age, body mass index, or opening pressure between the primary intracranial hypertension and secondary intracranial hypertension groups. Symptoms most often reported were headache and blurred vision. Bilateral optic disc edema occurred in 89.3% of primary intracranial hypertension and 78.7% of secondary intracranial hypertension patients. When divided into pre- and postpubertal status, 32.5% of patients were classified prepubertal; 77.3% of these had primary intracranial hypertension. This resulted in a female to male ratio of 1:1.04 for prepubertal and 6:1 for postpubertal primary intracranial hypertension patients. The body mass index was significantly higher in the postpubertal primary intracranial hypertension group (P = 0.0014). There was no significant difference in opening pressure. CONCLUSIONS: The common symptoms of intracranial hypertension, including headache, optic disc edema, and vision changes, occurred with similar frequencies in our cohort to those reported in the literature. In separate subanalyses, we found significantly higher rates of obesity in postpubertal females with primary intracranial hypertension. The female-to-male ratios in the postpubertal primary intracranial hypertension and secondary intracranial hypertension groups were higher than reported in the literature. PMID- 27255413 TI - Recent Advances in Resting-State Electroencephalography Biomarkers for Autism Spectrum Disorder-A Review of Methodological and Clinical Challenges. AB - BACKGROUND: Electroencephalography (EEG) has been used for almost a century to identify seizure-related disorders in humans, typically through expert interpretation of multichannel recordings. Attempts have been made to quantify EEG through frequency analyses and graphic representations. These "traditional" quantitative EEG analysis methods were limited in their ability to analyze complex and multivariate data and have not been generally accepted in clinical settings. There has been growing interest in identification of novel EEG biomarkers to detect early risk of autism spectrum disorder, to identify clinically meaningful subgroups, and to monitor targeted intervention strategies. Most studies to date have, however, used quantitative EEG approaches, and little is known about the emerging multivariate analytical methods or the robustness of candidate biomarkers in the context of the variability of autism spectrum disorder. METHODS: Here, we present a targeted review of methodological and clinical challenges in the search for novel resting-state EEG biomarkers for autism spectrum disorder. RESULTS: Three primary novel methodologies are discussed: (1) modified multiscale entropy, (2) coherence analysis, and (3) recurrence quantification analysis. Results suggest that these methods may be able to classify resting-state EEG as "autism spectrum disorder" or "typically developing", but many signal processing questions remain unanswered. CONCLUSIONS: We suggest that the move to novel EEG analysis methods is akin to the progress in neuroimaging from visual inspection, through region-of-interest analysis, to whole-brain computational analysis. Novel resting-state EEG biomarkers will have to evaluate a range of potential demographic, clinical, and technical confounders including age, gender, intellectual ability, comorbidity, and medication, before these approaches can be translated into the clinical setting. PMID- 27255414 TI - Two-Dimensional Sonographic Evaluation of Endometrial Polyps - Parameters That Are Reassuring. AB - AIMS: To assess intra-endometrial lesions according to five two-dimensional sonographic parameters for predicting malignancy. MATERIAL AND METHODS: This is a retrospective analysis of stored digital images from consecutive pathological reports of patients with benign endometrial polyps and stage 1 endometrial carcinoma. Five sonographic parameters were evaluated: heterogeneous or complex echogenicity of the lesion, presence of a 'bright edge sign,' regular endometrial myometrial junction, the presence of a normal endometrium adjacent to the lesion, and detection of small intralesional cysts. The sensitivity, specificity, PPV, and NPV of these parameters were calculated, as well as combinations of pairs of parameters. RESULTS: Seventy-nine patients were eligible for the current study, 26 with benign endometrial polyps and 53 with stage 1 endometrial carcinoma. The sonographic appearance of numerous small intralesional cysts (cystic formation) was highly related to benign polyp; the presence of a lesion with heterogeneous echogenicity had sensitivity and specificity for malignancy of 63.5 and 88.5%, respectively. CONCLUSIONS: We have shown that asymptomatic endometrial lesions, which are homogenous, have bright edges, and small intralesional cysts are likely to be benign Determining these parameters during sonographic evaluation can assist in identifying patients who will benefit from a follow-up strategy instead of an unnecessary surgical intervention. PMID- 27255415 TI - Atomic and electronic structure of Lomer dislocations at CdTe bicrystal interface. AB - Extended defects are of considerable importance in determining the electronic properties of semiconductors, especially in photovoltaics (PVs), due to their effects on electron-hole recombination. We employ model systems to study the effects of dislocations in CdTe by constructing grain boundaries using wafer bonding. Atomic-resolution scanning transmission electron microscopy (STEM) of a [1-10]/(110) 4.8 degrees tilt grain boundary reveals that the interface is composed of three distinct types of Lomer dislocations. Geometrical phase analysis is used to map strain fields, while STEM and density functional theory (DFT) modeling determine the atomic structure at the interface. The electronic structure of the dislocation cores calculated using DFT shows significant mid-gap states and different charge-channeling tendencies. Cl-doping is shown to reduce the midgap states, while maintaining the charge separation effects. This report offers novel avenues for exploring grain boundary effects in CdTe-based solar cells by fabricating controlled bicrystal interfaces and systematic atomic-scale analysis. PMID- 27255416 TI - Diagnostic accuracy of a TRAIL, IP-10 and CRP combination for discriminating bacterial and viral etiologies at the Emergency Department. PMID- 27255417 TI - In situ microscopic studies on the structures and phase behaviors of SF/PEG films using solid-state NMR and Raman imaging. AB - In order to overcome the drawbacks of silk fibroin (SF)-based materials, SF has been blended with some polymers. Before using the blend material, understanding of the structures and phase behaviors of the blend is thought to be essential. In this study, solid-state (13)C CP-MAS NMR and Raman imaging techniques were used to study the structures and phase behaviors of blends of SF with polyethylene glycol (PEG) at a molecular weight that varied from 2 to 20 kDa and a blend ratio of SF/PEG from 95/5 to 70/30 (w/w%) at the molecular and microscopic levels. It is found that the conformational transition of SF to the beta-sheet increased as the PEG content increased, while the amount of the formed beta-sheet conformers was decreased as the PEG molecular weight increased for a given content. It is also observed that SF was incompatible with PEG to some extent. The phase separation into "sea" and "island" domains took place in the SF/PEG blend films. SF was dominantly present in the "sea" domain, while PEG in the "island" domains. The conformation of SF in the interface between SF and PEG was changed to the beta-sheet, while that in the protein-rich domain remained in the random coil and/or helix conformation. These observations suggest that the specifically expected materials, for example, the silk-based microspheres or scaffold materials can be manufactured by controlling the molecular weight and content of PEG in the blend system. PMID- 27255418 TI - Response to: 'Issues with anti-Gr1 antibody-mediated myeloid-derived suppressor cell depletion' by Xing et al. PMID- 27255420 TI - Phase-Transformation-Induced Extra Thermal Expansion Behavior of (SrxBa1 x)TiO3/Cu Composite. AB - The properties of metal matrix composites (MMCs) can be optimized effectively through adjusting the type or the volume fraction of reinforcement. Generally, the coefficient of thermal expansion (CTE) of MMCs can be reduced by increasing the volume fraction of the reinforcement with lower CTE than metal matrix. However, it is great challenge to fabricate low CTE MMCs with low reinforcement volume fraction because of the limitation of reinforcement CTEs. SrxBa1-xTiO3 (SBT) powder presents negative thermal expansion behavior during the phase transformation from tetragonal to cubic phase. Here, we demonstrate that the phase transformation of SBT can be utilized to reduce and design the thermal expansion properties of SBT particle-reinforced Cu (SBT/Cu) composite, and ultralow CTE can be obtained in SBT/Cu composite. The X-ray diffraction analysis on heating indicates that the temperature range of phase transformation is extended greatly, therefore, the low CTE can be achieved within wide temperature range. Landau-Devonshire theory study on the phase transformation behaviors of SBT particles in the composite indicates that thermal mismatch stress significantly affects the Curie temperature of SBT particles and the CTE of the composite. The results given in the present study provide a new approach to design the MMCs with low CTE. PMID- 27255421 TI - Corrigendum: Radiocarbon constraints on the extent and evolution of the South Pacific glacial carbon pool. PMID- 27255419 TI - CXCL3 contributes to CD133(+) CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation. AB - Although the chemotactic cytokine CXCL3 is thought to play an important role in tumor initiation and invasion, little is known about its function in hepatocellular carcinoma (HCC). In our previous study, we found that Ikaros inhibited CD133 expression via the MAPK pathway in HCC. Here, we showed that Ikaros may indirectly down-regulate CXCL3 expression in HCC cells, which leads to better outcomes in patients with CD133(+) cancer stem cell (CSC) populations. CD133 overexpression induced CXCL3 expression, and silencing of CD133 down regulated CXCL3 in HCC cells. Knockdown of CXCL3 inhibited CD133(+) HCC CSCs' self-renewal and tumorigenesis. The serum CXCL3 level was higher in HCC patients' samples than that in healthy individual. HCC patients with higher CXCL3 expression displayed a poor prognosis, and a high level of CXCL3 was significantly associated with vascular invasion and tumor capsule formation. Exogenous CXCL3 induced Erk1/2 and ETS1 phosphorylation and promoted CD133 expression, indicating a positive feedback loop between CXCL3 and CD133 gene expression in HCC cells via Erk1/2 activation. Together, our findings indicated that CXCL3 might be a potent therapeutic target for HCC. PMID- 27255422 TI - Role of Chloride for a Simple, Non-Grignard Mg Electrolyte in Ether-Based Solvents. AB - Mg battery operates with Chevrel phase (Mo6S8, ~1.1 V vs Mg) cathodes that apply Grignard-based or derived electrolytes, which allow etching of the passivating oxide coating forms at the magnesium metal anode. Majority of Mg electrolytes studied to date are focused on developing new synthetic strategies to achieve a better reversible Mg deposition. While most of these electrolytes contain chloride as a component, and there is a lack of literature which investigates the fundamental role of chloride in Mg electrolytes. Further, ease of preparation and potential safety benefits have made simple design of magnesium electrolytes an attractive alternative to traditional air sensitive Grignard reagents-based electrolytes. Work presented here describes simple, non-Grignard magnesium electrolytes composed of magnesium bis(trifluoromethane sulfonyl)imide mixed with magnesium chloride (Mg(TFSI)2-MgCl2) in tetrahydrofuran (THF) and diglyme (G2) that can reversibly plate and strip magnesium. Based on this discovery, the effect of chloride in the electrolyte complex was investigated. Electrochemical properties at different initial mixing ratios of Mg(TFSI)2 and MgCl2 showed an increase of both current density and columbic efficiency for reversible Mg deposition as the fraction content of MgCl2 increased. A decrease in overpotential was observed for rechargeable Mg batteries with electrolytes with increasing MgCl2 concentration, evidenced by the coin cell performance. In this work, the fundamental understanding of the operation mechanisms of rechargeable Mg batteries with the role of chloride content from electrolyte could potentially bring rational design of simple Mg electrolytes for practical Mg battery. PMID- 27255423 TI - A Clinical Review of Return-to-Play Considerations After Anterior Shoulder Dislocation. AB - CONTEXT: Shoulder dislocations are common in contact sports, yet guidelines regarding the best treatment strategy and time to return to play have not been clearly defined. EVIDENCE ACQUISITION: Electronic databases, including PubMed, MEDLINE, and Embase, were reviewed for the years 1980 through 2015. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Much has been published about return to play after anterior shoulder dislocation, but almost all is derived from expert opinion and clinical experience rather than from well designed studies. Recommendations vary and differ depending on age, sex, type of sport, position of the athlete, time in the sport's season, and associated pathology. Despite a lack of consensus and specific recommendations, there is agreement that before being allowed to return to sport, athletes should be pain free and demonstrate symmetric shoulder and bilateral scapular strength, with functional range of motion that allows sport-specific participation. Return to play usually occurs 2 to 3 weeks from the time of injury. Athletes with in-season shoulder instability returning to sport have demonstrated recurrence rates ranging from 37% to 90%. Increased bone loss, recurrent instability, and injury occurring near the end of season are all indications that may push surgeons and athletes toward earlier surgical intervention. CONCLUSION: Most athletes are able to return to play within 2 to 3 weeks but there is a high risk of recurrent instability. PMID- 27255425 TI - Colin Deas Campbell. PMID- 27255424 TI - NHS England confirms it will not fund HIV prevention pill. PMID- 27255426 TI - Whole-genome resequencing of honeybee drones to detect genomic selection in a population managed for royal jelly. AB - Four main evolutionary lineages of A. mellifera have been described including eastern Europe (C) and western and northern Europe (M). Many apiculturists prefer bees from the C lineage due to their docility and high productivity. In France, the routine importation of bees from the C lineage has resulted in the widespread admixture of bees from the M lineage. The haplodiploid nature of the honeybee Apis mellifera, and its small genome size, permits affordable and extensive genomics studies. As a pilot study of a larger project to characterise French honeybee populations, we sequenced 60 drones sampled from two commercial populations managed for the production of honey and royal jelly. Results indicate a C lineage origin, whilst mitochondrial analysis suggests two drones originated from the O lineage. Analysis of heterozygous SNPs identified potential copy number variants near to genes encoding odorant binding proteins and several cytochrome P450 genes. Signatures of selection were detected using the hapFLK haplotype-based method, revealing several regions under putative selection for royal jelly production. The framework developed during this study will be applied to a broader sampling regime, allowing the genetic diversity of French honeybees to be characterised in detail. PMID- 27255428 TI - Ab initio calculations of mechanical properties of bcc W-Re-Os random alloys: effects of transmutation of W. AB - To examine the effect of neutron transmutation on tungsten as the first wall material of fusion reactors, the elastic properties of W1-x-y Re x Os y (0 ? x, y ? 6%) random alloys in body centered cubic (bcc) structure are investigated systematically using the all-electron exact muffin-tin orbitals (EMTO) method in combination with the coherent-potential approximation (CPA). The calculated lattice constant and elastic properties of pure W are consistent with available experiments. Both Os and Re additions reduce the lattice constant and increase the bulk modulus of W, with Os having the stronger effect. The polycrystalline shear modulus, Young's modulus and the Debye temperature increase (decrease) with the addition of Re (Os). Except for C 11, the other elastic parameters including C 12, C 44, Cauchy pressure, Poisson ratio, B/G, increase as a function of Re and Os concentration. The variations of the latter three parameters and the trend in the ratio of cleavage energy to shear modulus for the most dominant slip system indicate that the ductility of the alloy enhances with increasing Re and Os content. The calculated elastic anisotropy of bcc W slightly increases with the concentration of both alloying elements. The estimated melting temperatures of the W-Re-Os alloy suggest that Re or Os addition will reduce the melting temperature of pure W solid. The classical Labusch-Nabarro model for solid-solution hardening predicts larger strengthening effects in W1-y Os y than in W1-x Re x . A strong correlation between C' and the fcc-bcc structural energy difference for W1-x-y Re x Os y is revealed demonstrating that canonical band structure dictates the alloying effect on C'. The structural energy difference is exploited to estimate the alloying effect on the ideal tensile strength in the [0 0 1] direction. PMID- 27255427 TI - Optical diffraction for measurements of nano-mechanical bending. AB - We explore and exploit diffraction effects that have been previously neglected when modelling optical measurement techniques for the bending of micro-mechanical transducers such as cantilevers for atomic force microscopy. The illumination of a cantilever edge causes an asymmetric diffraction pattern at the photo-detector affecting the calibration of the measured signal in the popular optical beam deflection technique (OBDT). The conditions that avoid such detection artefacts conflict with the use of smaller cantilevers. Embracing diffraction patterns as data yields a potent detection technique that decouples tilt and curvature and simultaneously relaxes the requirements on the illumination alignment and detector position through a measurable which is invariant to translation and rotation. We show analytical results, numerical simulations and physiologically relevant experimental data demonstrating the utility of the diffraction patterns. We offer experimental design guidelines and quantify possible sources of systematic error in OBDT. We demonstrate a new nanometre resolution detection method that can replace OBDT, where diffraction effects from finite sized or patterned cantilevers are exploited. Such effects are readily generalized to cantilever arrays, and allow transmission detection of mechanical curvature, enabling instrumentation with simpler geometry. We highlight the comparative advantages over OBDT by detecting molecular activity of antibiotic Vancomycin. PMID- 27255429 TI - The lower body muscle activation of intermediate to experienced kayakers when navigating white water. AB - In white-water kayaking, the legs play a vital part in turning, stabilising and bracing actions. To date, there has been no reported information on neuromuscular activation of the legs in an authentic white-water environment. The aim of the current study was to identify lower body muscle activation, using 'in-boat' electromyography (EMG), whilst navigating a white-water run. Ten experienced male kayakers (age 31.5 +/- 12.5 yr, intermediate to advanced experience) completed three successful runs of an international standard white-water course (grade 3 rapids), targeting right and left sides of the course, in a zigzag formation. Surface EMG (sEMG) outputs were generated, bilaterally, for the rectus femoris (RF), vastus lateralis, biceps femoris and gastrocnemius, expressed as a percentage of a dynamic maximal voluntary contraction (dMVC). Only RF showed significantly higher activation than any muscle on the left side of the body, and only on the left side of the course (P = .004; ETA(2) = 0.56). Other results showed no significant difference between muscle activation in the right and left legs during each run, nor when assessed at either the right or left side of the course (P > .05). These findings indicate that contralateral symmetry in lower limb muscle activation is evident during white-water kayaking. This symmetry may provide a stable base to allow more asymmetrical upper body and trunk movements to be fully optimised. Lower body symmetry development should be considered useful in targeted training programmes for white-water kayakers. PMID- 27255430 TI - Diabetes mellitus, hypertension and frailty: A population-based, cross-sectional study of Mexican older adults. AB - AIM: Chronic diseases are frequent in older adults, particularly hypertension and diabetes. The relationship between frailty and these two conditions is still unclear. The aim of the present analyses was to explore the association between frailty with diabetes and hypertension in Mexican older adults. METHODS: Analyses of the Mexican Health and Nutrition Survey, a cross-sectional survey, are presented. Data on diabetes and hypertension were acquired along with associated conditions (time since diagnosis, pharmacological treatment, among others). A 36 item frailty index was constructed and rescaled to z-values (individual scores minus population mean divided by one standard deviation). Multiple linear regression models were carried out, adjusted for age and sex. RESULTS: From 7164 older adults, 54.8% were women, and their mean age was 70.6 years with a mean frailty index score of 0.175. The prevalence of diabetes was of 22.2%, and 37.3% for hypertension. An independent association between diabetes, hypertension or both conditions (coefficients 0.28, 0.4 and 0.63, respectively, P < 0.001) with frailty was found. Having any diabetic complication was significantly associated with frailty with a coefficient of 0.55 (95% CI 0.45-0.65, P < 0.001) in the adjusted model. The number of years since diagnosis was also associated with frailty for both conditions. CONCLUSIONS: Diabetes and hypertension are associated with frailty. In addition, an incremental association was found when both conditions were present or with worse associated features (any complication, more time since diagnosis). Frailty should be of particular concern in populations with a high prevalence of these conditions. Geriatr Gerontol Int 2017; 17: 925-930. PMID- 27255431 TI - Efficacy and safety of coadministration of sitagliptin with insulin glargine in type 2 diabetes. AB - BACKGROUND: The aim of the randomized present study was to compare the therapeutic efficacy and safety of a combination of sitagliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, plus insulin glargine (GL + sita) with that of premixed insulin aspart 30 (NOV) for type 2 diabetes (T2D) patients controlled with oral hypoglycemic drugs (HbA1c 7 %-9 %). METHODS: Sixty-five patients were randomized (1: 1) to the GL + sita (n = 33) and NOV (n = 32) groups and were treated with the combination regimen or premixed insulin twice a day for 16 weeks. The primary endpoint was mean change in HbA1c. Secondary endpoints included fasting blood glucose, blood glucose profiles (seven time points), rate of achieving target HbA1c (<7 % or <=6.5 %), insulin dose, incidence of hypoglycemia, and body weight. RESULTS: After 16 weeks, there was no significant difference in HbA1c between the two groups, although more patients achieved HbA1c <7.0 % in the GL + sita group. There was a significant difference in body weight changes between the GL + sita and NOV groups (-0.45 vs 1.52 kg, respectively; P < 0.001). Mean plasma glucose and the mean amplitude of glycemic excursion were significantly lower in the GL + sita than NOV group (P < 0.005), as was the incidence of symptomatic hypoglycemia (2.85 % vs. 13.3 %, respectively; P < 0.001). CONCLUSION: The combination of GL + sita greatly improved HbA1c in T2D patients (HbA1c 7 %-9 %) with an efficacy that was equal to that of premixed insulin. Thus, GL + sita treatment is a viable option for patients who fail to achieve glycemic control using oral hypoglycemic drugs. PMID- 27255432 TI - Gating Modulation of the Tumor-Related Kv10.1 Channel by Mibefradil. AB - Several reports credit mibefradil with tumor suppressing properties arising from its known inhibition of Ca2+ currents. Given that mibefradil (Mb) is also known to inhibit K+ channels, we decided to study the interaction between this organic compound and the tumor-related Kv10.1 channel. Here we report that Mb modulates the gating of Kv10.1. Mb induces an apparent inactivation from both open and early closed states where the channels dwell at hyperpolarized potentials. Additionally, Mb accelerates the kinetics of current activation, in a manner that depends on initial conditions. Our observations suggest that Mb binds to the voltage sensor domain of Kv10.1 channels, thereby modifying the gating of the channels in a way that in some, but not all, aspects opposes to the gating effects exerted by divalent cations. J. Cell. Physiol. 232: 2019-2032, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27255433 TI - Systematic Review of the Diagnostic Accuracy of Haptoglobin, Serum Amyloid A, and Fibrinogen versus Clinical Reference Standards for the Diagnosis of Bovine Respiratory Disease. AB - BACKGROUND: Bovine respiratory disease (BRD) is a worldwide animal health concern especially in feedlot, dairy, and veal calves. One of the greatest challenges is the absence of a gold standard for achieving an accurate antemortem diagnosis. Various blood markers, including the acute-phase proteins (AAP), have been proposed as potential valuable tools for BRD diagnosis. OBJECTIVES: To perform a systematic review of the literature to assess the accuracy of selected APP (haptoglobin [Hp], serum amyloid A [SAA], and fibrinogen [Fb]) as diagnostic tools for cattle with naturally occurring BRD when compared with clinical reference standards of diagnosis. METHODS: This review was performed with eligible studies selected from CAB Abstract and MEDLINE from 1946 to 2015, as well as the "gray literature." Methodological quality of included studies was assessed using the QUADAS-2 tool developed for diagnostic accuracy studies. The accuracy parameters sensitivity (Se) and specificity (Sp) were obtained from the articles or through contact with the authors when not directly reported. RESULTS: A total of 314 studies were identified, from them, 23 met inclusion criteria as diagnostic studies for naturally occurring BRD. Quality of studies showed high risk of bias for case selection (70% of articles) and unclear risk of bias for index test (65%), reference standard (74%), and flow and timing (61%). There were high concerns regarding applicability for case selection (61% of studies) and reference standards used for defining BRD (48%). The concerns regarding index test application were low (83% of the studies). Only 4-8 studies could be included in the meta-analysis for each APP. No pooled estimates or pooled accuracy measurements were performed due to the low number of studies and multiple differences between studies, including reference standard definitions. CONCLUSIONS AND CLINICAL IMPORTANCE: On the basis of these findings, it is not possible to make conclusions regarding the accuracy of APP for BRD diagnosis. The reporting of accuracy of APP for BRD detection is inconsistent among studies. Recommendations to improve capability for future meta-analyses in this area include reporting studies on diagnostic tests following the Standard for the Reporting of Diagnostic Accuracy Studies (STARD), as well as trying to standardize BRD definition across future studies. PMID- 27255434 TI - Effect of supplemented sericin on the development, cell number, cryosurvival and number of lipid droplets in cultured bovine embryos. AB - Sericin was investigated as an alternative to fetal bovine serum (FBS) for bovine embryo culture. In vitro matured oocytes were developed using 0.05%, 0.1% or 0.15% sericin. The developmental rate, cryosurvival rate and blastulation time of these embryos were compared with those of embryos developed using 5% FBS. The number of lipid droplets was compared among the blastocysts developed using 5% FBS, using 0.05% sericin and in vivo. The rate of cleavage and blastocyst formation was similar among all groups. Blastulation occurred significantly earlier in the embryos developed using 5% FBS than in those developed using sericin at any concentration (P < 0.05). At 72 h after thawing, the cryosurvival rate of the blastocysts developed using 5% FBS and 0.05% sericin were significantly higher compared with those developed using 0.1% and 0.15% sericin (P < 0.05). The blastocysts developed using 0.05% sericin and in vivo produced a significantly fewer number of medium and large lipid droplets than those developed using 5% FBS. These results suggest that the blastocysts developed using 0.05% sericin show characteristics similar to those of the blastocysts developed in vivo and that the use of sericin as an alternative to FBS is feasible. PMID- 27255435 TI - Scandinavian SSAI clinical practice guideline on pre-hospital airway management. AB - BACKGROUND: The Scandinavian society of anaesthesiology and intensive care medicine task force on pre-hospital airway management was asked to formulate recommendations following standards for trustworthy clinical practice guidelines. METHODS: The literature was systematically reviewed and the grading of recommendations assessment, development and evaluation (GRADE) system was applied to move from evidence to recommendations. RESULTS: We recommend that all emergency medical service (EMS) providers consider to: apply basic airway manoeuvres and airway adjuncts (good practice recommendation); turn unconscious non-trauma patients into the recovery position when advanced airway management is unavailable (good practice recommendation); turn unconscious trauma patients to the lateral trauma position while maintaining spinal alignment when advanced airway management is unavailable [strong recommendation, low quality of evidence (QoE)]. We suggest that intermediately trained providers use a supraglottic airway device (SAD) or basic airway manoeuvres on patients in cardiac arrest (weak recommendation, low QoE). We recommend that advanced trained providers consider using an SAD in selected indications or as a rescue device after failed endotracheal intubation (ETI) (good practice recommendation). We recommend that ETI should only be performed by advanced trained providers (strong recommendation, low QoE). We suggest that videolaryngoscopy is considered for ETI when direct laryngoscopy fails or is expected to be difficult (weak recommendation, low QoE). We suggest that advanced trained providers apply cricothyroidotomy in 'cannot intubate, cannot ventilate' situations (weak recommendation, low QoE). CONCLUSION: This guideline for pre-hospital airway management includes a combination of techniques applied in a stepwise fashion appropriate to patient clinical status and provider training. PMID- 27255436 TI - Conserved form and function of the germinal epithelium through 500 million years of vertebrate evolution. AB - The germinal epithelium, i.e., the site of germ cell production in males and females, has maintained a constant form and function throughout 500 million years of vertebrate evolution. The distinguishing characteristic of germinal epithelia among all vertebrates, males, and females, is the presence of germ cells among somatic epithelial cells. The somatic epithelial cells, Sertoli cells in males or follicle (granulosa) cells in females, encompass and isolate germ cells. Morphology of all vertebrate germinal epithelia conforms to the standard definition of an epithelium: epithelial cells are interconnected, border a body surface or lumen, are avascular and are supported by a basement membrane. Variation in morphology of gonads, which develop from the germinal epithelium, is correlated with the evolution of reproductive modes. In hagfishes, lampreys, and elasmobranchs, the germinal epithelia of males produce spermatocysts. A major rearrangement of testis morphology diagnoses osteichthyans: the spermatocysts are arranged in tubules or lobules. In protogynous (female to male) sex reversal in teleost fishes, female germinal epithelial cells (prefollicle cells) and oogonia transform into the first male somatic cells (Sertoli cells) and spermatogonia in the developing testis lobules. This common origin of cell types from the germinal epithelium in fishes with protogynous sex reversal supports the homology of Sertoli cells and follicle cells. Spermatogenesis in amphibians develops within spermatocysts in testis lobules. In amniotes vertebrates, the testis is composed of seminiferous tubules wherein spermatogenesis occurs radially. Emerging research indicates that some mammals do not have lifetime determinate fecundity. The fact emerged that germinal epithelia occur in the gonads of all vertebrates examined herein of both sexes and has the same form and function across all vertebrate taxa. Continued study of the form and function of the germinal epithelium in vertebrates will increasingly clarify our understanding of vertebrate reproduction. J. Morphol. 277:1014-1044, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27255437 TI - Recommended responsibilities for management of MR safety. PMID- 27255439 TI - Asbestos and product defence science. PMID- 27255438 TI - Cognitive and emotional outcomes after prolonged education: a quasi-experiment on 320 182 Swedish boys. AB - Background: Cognitive and socio-emotional abilities are powerful predictors of death and disease as well as of social and economic outcomes. Education is societies' main way of promoting these abilities, ideally so that inequalities by socioeconomic background are reduced. However, the extent to which education serves these cognitive, social-emotional and equality objectives is relatively unknown and intensively debated. Drawing on a Swedish school reform that was explicitly designed as a massive quasi-experiment, we assessed differential impact of education on intelligence and emotional control across childhood socioeconomic position. We also assessed initial differences in abilities by childhood socioeconomic position and how well childhood socioeconomic position and abilities predict all-cause mortality. Methods: The Swedish comprehensive school reform, rolled out during the 1950s, extended compulsory education from 8 to 9 years in some municipalities whereas others were kept as controls for the sake of evaluation. We followed eight full cohorts of Swedish boys born between 1951 and 1958, who lived in 1017 municipalities with known experimental status (344 336 boys) and whose childhood socioeconomic position was known (320 182 boys). At conscription, intelligence was measured by four subtests and emotional control (calm and efficient responses in various situations) was rated by a military psychologist. Both measures were standardized to have a mean of 100 and standard deviation of 15. All-cause mortality was recorded until 49-56 years of age. Results: The reform had an average positive impact on intelligence of 0.75 IQ units (95% confidence interval (CI): 0.54, 0.97; P < 0.0005). The impact on emotional control was negative; -0.50 units (95% CI: -0.72, -0.28; P < 0.0005). Both effects differed by socioeconomic background so that the average IQ difference between sons of high non-manual and unqualified manual workers was reduced from 16.32 to 15.57 units and the difference in emotional control was reduced from 6.50 to 5.63 units. All-cause mortality was predicted by low childhood socioeconomic position [hazard ratio (HR) = 1.15 [95% CI: 1.11, 1.20], P < 0.0005], low intelligence [HR = 1.39 (95% CI: 1.34, 1.44), P < 0.0005] as well as low emotional control [HR = 1.61 (95% CI: 1.55, 1.67), P < 0.0005] in mutually adjusted models. Conclusions: Extending compulsory education promoted intelligence but lowered emotional control, and reduced disparities over social background in both. Emotional control was the strongest predictor of all-cause mortality. Our results are in line with the idea that education is important in our efforts to achieve healthy, competent and fair societies, but much more work is needed to understand the links between education and non-cognitive skills. PMID- 27255440 TI - Lessons from a decade of suicide surveillance in India: who, why and how? AB - Background: This paper investigates trends in suicide rate, the reasons for and means of suicide and the occupation of deceased, to prioritize suicide prevention activities in India and to highlight the limitations to data quality for surveillance. Methods: Data available in the public domain from the National Crimes Record Bureau (NCRB) were analysed from 2001 to 2010 at the national and sub-national levels, split by age groups and sex for ages 15 years and above. Results: The reported suicide rate was 14.9 and 15.4 suicides per 100 000 population in 2001 and 2010, respectively. More developed states reported significantly higher suicide rates than the less developed (mean 20.5 versus 8.16), but neither experienced large changes over time. Among males, the reported suicide rate changed slightly (17.8 to 19.5); it remained almost similar for females (11.9 to 11.1). Housewives accounted for the highest proportion of suicide deaths over the decade. Distribution of the reasons for suicide remained almost constant over time; most suicides (33.7%) were due to personal/social reasons, followed by health at 24.3% and unknown reasons at 16.4%; differences were observed between the more and less developed states. Marriage-related suicides were higher for females, and health reasons increased with increasing age. Nationally, poison/overdose with drugs/pesticides was the leading means of suicide through the decade, although the gap between this and hanging decreased over time. The state level data showed considerable heterogeneity in the quality of data across the indicators assessed. Conclusions: These data provide a range of information to identify vulnerable groups, to formulate appropriate suicide prevention strategies. Addressing the limitations in data quality would facilitate further utility of surveillance data to prevent suicides. PMID- 27255441 TI - Actinomadura montaniterrae sp. nov., isolated from mountain soil. AB - The taxonomic position of the mountain soil actinomycete, strain CYP1-1BT, was clarified by a polyphasic study. The strain produced a single spore, or occasionally a chain of spores, on aerial mycelium. Chemotaxonomic data supported the classification of CYP1-1BT as representing a member of the genus Actinomadura on the basis of the presence of meso-diaminopimelic acid in the peptidoglycan; galactose, glucose, madurose and ribose as whole cell sugars; MK-9(H6), MK-9(H8) and MK-9(H4) as dominant menaquinones; C16 : 0, 10-methylated C18 : 0 and C18 : 1omega9c as the major cellular fatty acids; and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol manosides as the predominant phospholipids. The DNA G+C content was 74.3 mol%. On the basis of the combination of morphological and chemotaxonomic characteristics, CYP1-1BT was identified as representing a member of the genus Actinomadura. On the basis of the results of 16S rRNA gene analysis, CYP1-1BT, was shown to be closely related to Actinomadura nitritigenes DSM 44137T (98.9 %). Phenotypic, genotypic and DNA DNA hybridization data supported the hypothesis that CYP1-1BT represents a novel species of the genus Actinomadura for which the name Actinomadura montaniterrae sp. nov. is proposed. The type strain is CYP1-1BT (=JCM 16995T=KCTC 39784T=PCU 349T=TISTR 2400T). PMID- 27255442 TI - Oxidative Inactivation of Liver Mitochondria in High Fructose Diet-Induced Metabolic Syndrome in Rats: Effect of Glycyrrhizin Treatment. AB - Metabolic syndrome is a serious health problem in the present world. Glycyrrhizin, a triterpenoid saponin of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate the primary complications and hepatocellular damage in rats with the syndrome. In this study, we have explored metabolic syndrome induced changes in liver mitochondrial function and effect of glycyrrhizin against the changes. Metabolic syndrome was induced in rats by high fructose (60%) diet for 6 weeks. The rats were then treated with glycyrrhizin (50 mg/kg body weight) by single intra-peritoneal injection. After 2 weeks of the treatment, the rats were sacrificed to collect liver tissue. Elevated mitochondrial ROS, lipid peroxidation and protein carbonyl, and decreased reduced glutathione content indicated oxidative stress in metabolic syndrome. Loss of mitochondrial inner membrane cardiolipin was observed. Mitochondrial complex I activity did not change but complex IV activity decreased significantly. Mitochondrial MTT reduction ability, membrane potential, phosphate utilisation and oxygen consumption decreased in metabolic syndrome. Reduced mitochondrial aconitase activity and increased aconitase carbonyl content suggested oxidative damage of the enzyme. Elevated Fe(2+) ion level in mitochondria might be associated with increased ROS generation in metabolic syndrome. Glycyrrhizin effectively attenuated mitochondrial oxidative stress and aconitase degradation, and improved electron transport chain activity. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27255443 TI - RKIP expression of liver and kidney after arsenic exposure. AB - Arsenic is associated with cancers of kidney and liver. Raf kinase inhibitor protein (RKIP) has been identified as a member of a novel class of molecules that suppress the metastatic spread of tumors. In order to investigate the effect of arsenic to RKIP of liver and kidney, the expression of RKIP of liver and kidney with As (III) was explored in this study. Thirty male mice were chronically fed with 42.5 ppm, 85 ppm NaAsO2 and water for 180 days. The kidney and liver accumulation levels of As (III) in mice were determined by electro-thermal atomic absorption spectrometry. The method of RT-PCR, Western blotting analysis and immunohistochemistry were used to determine gene expression and protein expression of RKIP. The results showed that arsenic level was significantly increased in kidney and liver of As (III)-exposed mice as compared with control group. The gene expression and protein expression of RKIP was significantly decreased in kidney and liver of As (III)-exposed mice in comparison with these of control mice. These data suggested that RKIP decrease of liver and kidney with As (III) may be dangerous index in formation of cancer. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1079-1082, 2017. PMID- 27255444 TI - Interstitial 1q23.3q24.1 deletion in a patient with renal malformation, congenital heart disease, and mild intellectual disability. AB - Interstitial deletions including chromosome region 1q23.3q24.1 are rare. Only eight patients with molecularly characterized deletions have been reported to date. Their phenotype included intellectual disability/developmental delay, growth retardation, microcephaly, congenital heart disease, and renal malformations. We report on a female patient with mild developmental delay, congenital heart disease, and bilateral renal hypoplasia in whom an interstitial de novo deletion of approximately 2.7 Mb in 1q23.3q24.1 was detected by array CGH. This is the smallest deletion described in this region so far. Genotype phenotype comparison with previously published patients allowed us to propose LMX1A and RXRG as potential candidate genes for intellectual disability, PBX1 as a probable candidate gene for renal malformation, and enabled us to narrow down a chromosome region associated with microcephaly. (c) 2016 Wiley Periodicals, Inc. PMID- 27255445 TI - Discordant anomalies and karyotype in a monochorionic twin pregnancy: a call for comprehensive genetic evaluation. PMID- 27255447 TI - Conditioned breathing depression during neonatal life as a function of associating ethanol odor and the drug's intoxicating effects. AB - Fetal and neonatal ethanol-related alterations upon the respiratory system have been described in different mammals. Studies also indicate that perinates learn about the sensory attributes of ethanol and associate them with diverse physiological effects of the state of intoxication. The present study was conducted in rat neonates during a developmental stage equivalent to the third human gestational trimester. The major goal was to analyze the consequences of ethanol odor exposure, the state of intoxication, or the temporal contiguity between these factors upon breathing patterns. The main findings were as follows: (a) a conditioned breathing depression was observed following few trials defined by the association between ethanol odor and the state of intoxication and (b) sequential exposure to ethanol sensitizes the organism to the drug's respiratory depressant effects without affecting ethanol metabolism. These results indicate that early breathing disruptions caused by ethanol can be determined or modulated via learning processes. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:670 686, 2016. PMID- 27255446 TI - [Choosing wisely together with the patient]. AB - Within the framework of the Choosing wisely initiative of the German Society for Internal Medicine, all scientific societies associated with internal medicine were requested to highlight the unnecessary or underused medical tests or procedures out of the 60 defined examples, which are of immediate relevance within the doctor-patient interaction. Each of the 12 scientific internal medicine societies compiled and substantiated 2 recommendations. This resulted in a spectrum of important recommendations covering the entire field of internal medicine. In difficult situations these recommendations should contribute to developing and supporting the dialogue with patients on an evidence-based level. PMID- 27255448 TI - The efficacy of simultaneous bilateral axillary brachial plexus block under the guidance of neurostimulator or ultrasound: a prospective study. AB - PURPOSE: This study was designed to investigate the risk of local anesthetic toxicity and efficacy of simultaneous bilateral axillary brachial plexus block performed under the guidance of ultrasound or a neurostimulator. METHODS: One hundred and twenty patients who were anesthetized with bilateral axillary plexus block simultaneously between February 2012 and March 2014 were enrolled in the study. The patients were anesthetized under the guidance of a neurostimulator (group N, n = 60) or ultrasound (group U, n = 60). The block performance time, procedure-related pain, adverse events, total and free plasma concentrations of ropivacaine, and other data were recorded. The comparison was analyzed statistically. RESULTS: The block performance time, and onset of the sensory and motor block, of group N was longer than that of group U (p < 0.001). The procedure-related pain of group N was more serious than that of group U (p < 0.05). The patient satisfaction rate of group U was higher than that of group N (p < 0.05). The total plasma concentrations of ropivacaine in group N were comparable to those of group U, except for the value at 50 min after injection (p < 0.05). The free plasma concentrations of ropivacaine of group N at 5 min were significantly higher than that of group U (p < 0.001). No apparent serious adverse events were observed perioperatively in both groups. CONCLUSIONS: Simultaneous bilateral axillary brachial plexus block guided by neurostimulator or ultrasound in bilateral distal upper extremity surgery seems to have a low risk of local anesthetic toxicity and to be effective. The ultrasound-guided block is superior in terms of providing the same degree of anesthesia with shorter duration, less pain, and faster onset of sensory and motor blockades, which is important in clinical practice. PMID- 27255449 TI - Sevoflurane anesthetic preconditioning protects the lung endothelial glycocalyx from ischemia reperfusion injury in an experimental lung autotransplant model. AB - PURPOSE: The glycocalyx is a glycoprotein-polysaccaride layer covering the endothelium luminal surface, and plays a key regulatory role in several endothelial functions. Lung ischemia reperfusion (IR) is a clinical entity that occurs in everyday thoracic surgery and causes glycocalix destruction and a florid local and systemic immune response. Moreover, sevoflurane is able to modulate the inflammatory response triggered by IR lung injury. In this study, we evaluated the protective effects of sevoflurane on the pulmonary endothelial glycocalyx in an in-vivo lung autotransplant model in pigs. METHODS: Sixteen Large White pigs underwent pneumonectomy plus lung autotransplant. They were divided into two groups depending on the hypnotic agent received (propofol or anesthetic preconditioning with sevoflurane). Glycocalyx components (syndecan-1 and heparan sulphate), cathepsin B, chemokines (MCP-1, MIP-1, and MIP-2) and adhesion molecules (VCAM and ICAM-1) were measured at four different timepoints using porcine-specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: There were no differences between groups in weight or in surgical and one-lung ventilation time. Greater glycocalyx destruction and higher chemokine and adhesion molecule expression were observed in the group that did not receive sevoflurane. Heparan sulphate and serum syndecan levels were higher in the propofol group (P < 0.0001) after reperfusion, as was cathepsin B activity (P < 0.015). MCP-1, MIP-1, MIP-2, VCAM, and ICAM-1 levels were also higher in the propofol group (P < 0.006). CONCLUSION: Sevoflurane preconditioning protects pulmonary glycocalyx and reduces expression of leukocyte chemokines in an in-vivo model of pulmonary IR. PMID- 27255450 TI - The isolation and the characterization of two polysaccharides from the branch bark of mulberry (Morus alba L.). AB - Two water-soluble polysaccharides termed MBBP-1 and MBBP-2 were isolated from the branches of the mulberry tree (Morus alba L.) using hot water extraction and purified on Anion-exchange DEAE52-cellulose and Sephadex G-100 column. MBBP-1 was shown to be composed of rhamnose, xylose, arabinose, mannose, glucose and galactose in the molar ratio of 4.53:2.49:4.38:4.67:17.85:5.88. MBBP-2 was composed of rhamnose, xylose, arabinose, mannose, glucose, galactose and galacturonic acid in the molar ratio of 26.85:13.8:3.14:4.4:6.1:3.19:4.9. Their structural characteristics were further investigated by FI-IR spectroscopy, Smith degradation, methylation analysis and NMR spectroscopy. Based on the data obtained, MBBP-1 had a backbone mainly consisting of (1 -> 3)-linked glucose. MBBP-2 had a backbone mainly consisting of (1 -> 3)-linked rhamnose and (1 -> 2, 4)-linked xylose. Antioxidant assays indicated that antioxidant activities of MBBP-2 were significantly stronger than those of MBBP-1, and this was likely in relation to the different content of 8.2 % galacturonic acid in MBBP-2. PMID- 27255451 TI - Number of pegs influence focal stress distributions and micromotion in glenoid implants: a finite element study. AB - The present study was conducted to compare the stability of four commercially available implants by investigating the focal stress distributions and relative micromotion using finite element analysis. Variations in the numbers of pegs between the implant designs were tested. A load of 750 N was applied at three different glenoid positions (SA: superior-anterior; SP: superior-posterior; C: central) to mimic off-center and central loadings during activities of daily living. Focal stress distributions and relative micromotion were measured using Marc Mentat software. The results demonstrated that by increasing the number of pegs from two to five, the total focal stress volumes exceeding 5 MPa, reflecting the stress critical volume (SCV) as the threshold for occurrence of cement microfractures, decreased from 8.41 to 5.21 % in the SA position and from 9.59 to 6.69 % in the SP position. However, in the C position, this change in peg number increased the SCV from 1.37 to 5.86 %. Meanwhile, micromotion appeared to remain within 19-25 um irrespective of the number of pegs used. In conclusion, four-peg glenoid implants provide the best configuration because they had lower SCV values compared with lesser-peg implants, preserved more bone stock, and reduced PMMA cement usage compared with five-peg implants. PMID- 27255452 TI - Mechanobiological simulations of peri-acetabular bone ingrowth: a comparative analysis of cell-phenotype specific and phenomenological algorithms. AB - Several mechanobiology algorithms have been employed to simulate bone ingrowth around porous coated implants. However, there is a scarcity of quantitative comparison between the efficacies of commonly used mechanoregulatory algorithms. The objectives of this study are: (1) to predict peri-acetabular bone ingrowth using cell-phenotype specific algorithm and to compare these predictions with those obtained using phenomenological algorithm and (2) to investigate the influences of cellular parameters on bone ingrowth. The variation in host bone material property and interfacial micromotion of the implanted pelvis were mapped onto the microscale model of implant-bone interface. An overall variation of 17 88 % in peri-acetabular bone ingrowth was observed. Despite differences in predicted tissue differentiation patterns during the initial period, both the algorithms predicted similar spatial distribution of neo-tissue layer, after attainment of equilibrium. Results indicated that phenomenological algorithm, being computationally faster than the cell-phenotype specific algorithm, might be used to predict peri-prosthetic bone ingrowth. The cell-phenotype specific algorithm, however, was found to be useful in numerically investigating the influence of alterations in cellular activities on bone ingrowth, owing to biologically related factors. Amongst the host of cellular activities, matrix production rate of bone tissue was found to have predominant influence on peri acetabular bone ingrowth. PMID- 27255454 TI - Public perceptions of snakes and snakebite management: implications for conservation and human health in southern Nepal. AB - BACKGROUND: Venomous snakebite and its effects are a source of fear for people living in southern Nepal. As a result, people have developed a negative attitude towards snakes, which can lead to human-snake conflicts that result in killing of snakes. Attempting to kill snakes increases the risk of snakebite, and actual killing of snakes contributes to loss of biodiversity. Currently, snake populations in southern Nepal are thought to be declining, but more research is needed to evaluate the conservation status of snakes. Therefore, we assessed attitudes, knowledge, and awareness of snakes and snakebite by Chitwan National Park's (CNP) buffer zone (BZ) inhabitants in an effort to better understand challenges to snake conservation and snakebite management. The results of this study have the potential to promote biodiversity conservation and increase human health in southern Nepal and beyond. METHODS: We carried out face-to-face interviews of 150 randomly selected CNP BZ inhabitants, adopting a cross sectional mixed research design and structured and semi-structured questionnaires from January-February 2013. RESULTS: Results indicated that 43 % of respondents disliked snakes, 49 % would exterminate all venomous snakes, and 86 % feared snakes. Farmers were the most negative and teachers were the most ambivalent towards snakes. Respondents were generally unable to identify different snake species, and were almost completely unaware of the need of conserve snakes and how to prevent snakebites. Belief in a snake god, and the ability of snakes to absorb poisonous gases from the atmosphere were among many superstitions that appeared to predispose negativity towards snakes of BZ residents. CONCLUSION: People with predisposed negativity towards snakes were not proponents of snake conservation. Fear, negativity, ambivalence towards, and ignorance about, snakes and the need for snake conservation were strong indicators of the propensity to harm or kill snakes. It seems that if wanton killing of snakes continues, local snake populations will decline, and rare and endangered snake species may even become locally extirpated. Moreover, inappropriate perception and knowledge about snakes and snakebites may put BZ people at increased risk of venomous snakebite. Therefore, intensive, pragmatic educational efforts focused on natural history and ecology of snakes and prevention of snakebite should be undertaken in communities and at schools and universities. PMID- 27255455 TI - Biodegradable Smart Nanogels: A New Platform for Targeting Drug Delivery and Biomedical Diagnostics. AB - Nanogels (or nanohydrogels) have been extensively investigated as one of the most promising nanoparticulate biomedical platforms owing to their advantageous properties that combine the characteristics of hydrogel systems with nanoparticles. Among them, smart nanogels that have the ability to respond to external stimuli, such as pH, redox, temperature, enzymes, light, magnetic field and so forth, are most attractive in the area of drug delivery. Besides, numerous multifunctionalized nanogels with high sensitivity and specificity were designed for diagnostic applications. In this feature article, we have reviewed and discussed the recent progress of biodegradable nanogels as smart nanocarriers of anticancer drugs and biomedical diagnostic agents for cancer. PMID- 27255453 TI - Gene expression profiling of midbrain dopamine neurons upon gestational nicotine exposure. AB - Maternal smoking during pregnancy is associated with low birth weight, increased risk of stillbirth, conduct disorder, attention-deficit/hyperactivity disorder and neurocognitive deficits. Ventral tegmental area dopamine (DA) neurons in the mesocorticolimbic pathway were suggested to play a critical role in these pathological mechanisms induced by nicotine. Nicotine-mediated changes in genetic expression during pregnancy are of great interest for current researchers. We used patch clamp methods to identify and harvest DA and non-DA neurons separately and assayed them using oligonucleotide arrays to elucidate the alterations in gene expressions in these cells upon gestational nicotine exposure. Microarray analysis identified a set of 135 genes as significantly differentially expressed between DA and non-DA neurons. Some of the genes were found to be related to neurological disease pathways, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Significantly up-/down-regulated genes found in DA neurons were mostly related to G-protein-coupled protein receptor signaling and developmental processes. These alterations in gene expressions may explain, partially at least, the possible pathological mechanisms for the diseases induced by maternal smoking. PMID- 27255456 TI - Efficacy of the Hydroalcoholic Extract of Tribulus terrestris on the Serum Glucose and Lipid Profile of Women With Diabetes Mellitus: A Double-Blind Randomized Placebo-Controlled Clinical Trial. AB - AIM: Considering traditional use of Tribulus terrestris in diabetes and proven antihyperglycemic and antihyperlipidemic effects of T terrestris in animal studies, we aimed to evaluate the efficacy of the hydroalcoholic extract of T terrestris on the serum glucose and lipid profile of women with non-insulin dependent diabetes mellitus. METHODS: Ninety-eight women with diabetes mellitus type 2 were randomly allocated to receive the T terrestris (1000 mg/d) or placebo for 3 months. The patients were evaluated in terms of the fasting blood glucose, 2-hour postprandial glucose, glycosylated hemoglobin, and lipid profile. RESULTS: Tribulus terrestris showed a significant blood glucose-lowering effect in diabetic women compared to placebo (P < .05). Also, the total cholesterol and low density lipoprotein of T terrestris group was significantly reduced compared with placebo, while no significant effect was observed in the triglyceride and high density lipoprotein levels. CONCLUSIONS: The study showed preliminary promising hypoglycemic effect of T terrestris in women with diabetes mellitus type 2. PMID- 27255457 TI - Disentangling the concept of "the complex older patient" in general practice: a qualitative study. AB - BACKGROUND: The rising life expectancy in the developed world leads to an increase in the number of older patients and the complexity of their complaints in general practice. Although interventions and support for general practitioners are available, implementation lags. Knowledge on what determines a complex older patient, the problems of which general practitioners encounter and the situations they actually need support for, is necessary for better implementation. METHODS: To provide support to general practitioners in their struggle with complex older patients, the aim of this research was to disentangle the concept of the complex older patient in general practice. A qualitative approach was used consisting of 15 semi-structured interviews with general practitioners. The general practitioner was asked to prepare a case of a complex older patient out of their own practice that could be discussed during the interview. Transcripts of the interview were analysed using inductive thematic analysis. RESULTS: Analysis of the interviews resulted in twelve themes that could be categorised into five factors that contribute to the complexity of cases of older patients. The five factors are: not being in charge, different views on necessary care, encountering the boundaries of medicine, limits to providing social care, ill-equipped. CONCLUSION: The factors that were found imply that a better organisational structure for elderly care and consulting elderly care physicians could support general practitioners in providing care for older complex patients. Furthermore, understanding the current concept of patient autonomy seems unjustified in cases of complex older patients. PMID- 27255458 TI - Correlation between outer retinal layer thickness and cone density in patients with resolved central serous chorioretinopathy. AB - PURPOSE: We aimed to observe photoreceptors and outer retinal layer thickness by using an adaptive optics (AO) fundus camera and spectral domain optical coherence tomography (SD-OCT) in patients with central serous chorioretinopathy (CSC). METHODS: Twelve eyes of 12 patients with resolved CSC were studied. After subretinal fluid (SRF) had resolved, AO images of the macula were obtained by using the rtx1TM AO fundus camera (Imagine Eyes, France). Cones in the nasal and temporal areas of the macula, 0.5 mm from the foveal center, were counted. Outer retinal layer thickness was measured as the distance between the outer border of external limiting membrane (ELM) and the inner border of retinal pigment epithelium (RPE) at 0.5 mm from the foveal center. The first measurement was performed after resolution of the subretinal fluid and was defined as the baseline. Then, the second measurement was performed in the same location after 12 months. RESULTS: In the eyes with resolved CSC, the mean logMAR values of visual acuity at baseline and 12 months were 0.16 and 0.01, respectively (p = 0.0023). The mean cone densities at baseline and 12 months were 12,213 and 17,146 cones/mm2, respectively. The mean cone densities at 12 months were significantly increased compared to baseline (p = 0.0014). The mean outer retinal layer thickness at baseline (53.5 MUm) was significantly thinner than that at 12 months (60.7 MUm) (p = 0.0013). The mean cone densities were significantly correlated with outer retinal layer thickness and logMAR visual acuity. CONCLUSIONS: Adaptive optics imaging revealed a gradual increase in the number of macular cone densities during 12 months in patients with resolved CSC, which was correlated with outer retinal layer thickness and visual acuity in a short term. PMID- 27255459 TI - Retinal vessel diameter in bilateral glaucoma suspects: comparison between the eye converted to glaucoma and the contralateral non-converted eye. AB - PURPOSE: To investigate retinal vessel diameter in patients classified as bilateral glaucoma suspects who showed unilateral glaucomatous conversion. METHODS: This retrospective study included 21 patients who had initially been diagnosed as bilateral glaucoma suspects but showed unilateral glaucomatous conversion during a follow-up period of more than 2 years. Conversion to glaucoma was determined either by documentation of a new retinal nerve fiber layer defect on red-free photography or a reproducible glaucomatous visual field defect. The central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured from fundus photographs taken at baseline and at the point of glaucoma conversion. RESULTS: The mean CRAE of the converted eyes was significantly lower than that of the non-converted eyes at baseline (164.9 +/ 13.2 MUm vs 175.2 +/- 15.6 MUm; p = 0.001), but no significant difference was observed in the mean CRVE (p = 0.108). The mean CRAE of the converted eyes was also lower than in the non-converted eyes at the point of glaucoma conversion (158.6 +/- 13.5 MUm vs 168.0 +/- 17.2 MUm; p = 0.011). CONCLUSION: In bilateral glaucoma suspects, there was a significant inter-eye difference in CRAE at baseline between eyes that converted to glaucoma and those that did not. These findings suggest that measurement of retinal arteriolar diameter may help clinicians when evaluating the risk of conversion in glaucoma suspects. PMID- 27255460 TI - Evaluation of the retinal ganglion cell and choroidal thickness in young Turkish adults with hyperopic anisometropic amblyopia. PMID- 27255461 TI - Outcome of 2 cc pure sulfur hexafluoride gas tamponade for macular hole surgery. AB - BACKGROUND: Isoexpansile concentrations of intraocular gases are typically used as tamponading agent in macular hole surgery. Using a small volume of the pure form of these gases may achieve the same result without increasing the incidence of postoperative complications. The purpose of this study was to evaluate the anatomical and visual outcomes following macular hole surgery with 2 cc pure (100 %) sulfur hexafluoride (SF6) gas tamponade. METHODS: A retrospective study of eyes with idiopathic macular holes that underwent 23-gauge pars plana vitrectomy with 2 cc pure SF6 gas tamponade. Macular hole surgery was performed alone or in combination with phacoemulsification in eyes with cataract. Preoperative and postoperative data including best corrected visual acuity recorded in LogMAR units, slit-lamp biomicroscopy, and optical coherence tomography were analysed. Surgical complications were also recorded. RESULTS: Seventy six eyes of seventy five patients were analysed. A closure rate of 100 % was achieved with reoperation in 4 eyes. There was a significant improvement in best-corrected visual acuity from a mean of 0.65 LogMAR preoperatively to 0.36 at 6 months (p value 0.004). Forty five (59 %) eyes gained at least 2 lines on the Snellen visual acuity chart. Postoperative elevation in intraocular pressure (>=30 mmHg) was documented in 3 eyes (4 %). CONCLUSION: Macular hole surgery with 2 cc pure SF6 gas tamponade achieved a high success rate with a low incidence of complications. The smaller volume of gas required makes it a cheaper technique. PMID- 27255462 TI - Standardizing disease-specific quality of life measures across multiple chronic conditions: development and initial evaluation of the QOL Disease Impact Scale (QDIS(r)). AB - BACKGROUND: To document the development and evaluation of the Quality of life Disease Impact Scale (QDIS(r)), a measure that standardizes item content and scoring across chronic conditions and provides a summary, norm-based QOL impact score for each disease. METHODS: A bank of 49 disease impact items was constructed from previously-used descriptions of health impact to represent ten frequently-measured quality of life (QOL) content areas and operational definitions successfully utilized in generic QOL surveys. In contrast to health in general, all items were administered with attribution to a specific disease (osteoarthritis, rheumatoid arthritis, angina, myocardial infarction, congestive heart failure, chronic kidney disease (CKD), diabetes, asthma, or COPD). Responses from 5418 adults were analyzed as five disease groups: arthritis, cardiovascular, CKD, diabetes, and respiratory. Unidimensionality, item parameter and scale-level invariance, reliability, validity and responsiveness to change during 9-month follow-up were evaluated by disease group and for all groups combined using multi-group confirmatory factor analysis (MGCFA), item response theory (IRT) and analysis of variance methods. QDIS was normed in an independent chronically ill US population sample (N = 4120). RESULTS: MGCFA confirmed a 1 factor model, justifying a summary score estimated using equal parameters for each item across disease groups. In support of standardized IRT-based scoring, correlations were very high between disease-specific and standardized IRT item slopes (r = 0.88-0.96), thresholds (r = 0.93-0.99) and person-level scores (r >= 0.99). Internal consistency, test-retest and person-level IRT reliability were consistently satisfactory across groups. In support of interpreting QDIS as a disease-specific measure, in comparison with generic measures, QDIS consistently discriminated markedly better across disease severity levels, correlated higher with other disease-specific measures in cross-sectional tests, and was more responsive in comparisons of groups with better, same or worse evaluations of disease-specific outcomes at the 9-month follow-up. CONCLUSIONS: Standardization of content and scoring across diseases was shown to be justified psychometrically and enabled the first summary measure of disease-specific QOL impact normed in the chronically ill population. This disease-specific approach substantially improves discriminant validity and responsiveness over generic measures and provides a basis for better understanding the relative QOL impact of multiple chronic conditions in research and clinical practice. PMID- 27255463 TI - Partnered pharmacist charting on admission in the General Medical and Emergency Short-stay Unit - a cluster-randomised controlled trial in patients with complex medication regimens. AB - WHAT IS KNOWN AND OBJECTIVE: Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. METHODS: We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. RESULTS: Of the 473 patients who received standard medical staff charting during the study period, 372 (78.7%) had at least one medication error identified compared to 15 patients (3.7%) on the partnered pharmacist charting arm (P < 0.001). The relative risk of an error with standard medical charting was 21.4 (95% CI: 13.0 35.0) with a number needed to treat (NNT) to prevent one error of 1.3 (95% CI: 1.3-1.4), and the relative risk of a high or extreme risk error with standard medical charting was 150.9 (95% CI: 21.2-1072.9) with a NNT to prevent one high or extreme error of 2.7 (95% CI 2.4-3.1). WHAT IS NEW AND CONCLUSION: Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy. PMID- 27255464 TI - Caring for frail older people in the last phase of life - the general practitioners' view. AB - BACKGROUND: Frail older people are an increasingly important group in primary care due to demographic change. For these patients, a palliative care approach may be useful to sustain the quality of life in the last phase of their lives. While general practitioners (GPs) play a key role in the primary care for older patients, general palliative care is still in its infancy and little is known in Germany about caring for frail older people towards the end of life. This study aims to explore the tasks and challenges regarding the care for frail older patients in the last phase of life from the GPs' point of view, and the latter's perception of their own role and responsibilities. METHODS: Explorative qualitative study based on semi-structured in-depth interviews with 14 GPs from urban and rural regions in Lower Saxony, Germany. Analysis was carried out according to the principles of Grounded Theory. RESULTS: The GPs' key commitment "caring for frail older patients until the end" as an integral part of primary care was worked out as a key category, flanked by central issues: "causal conditions and challenges," which include patients' preconditions and care needs as well as communication and cooperation aspects on the carers' level. "Barriers and facilitators within the health system" refers to prerequisites of the German healthcare system, such as high caseloads. Regarding "strategies to comply with this commitment", various self-developed strategies for the care of frail older people are presented, depending on the GPs' understanding of their professional role and individual circumstances. CONCLUSIONS: The GPs show a strong commitment to caring for the frail older patients until the end of life. However, it is a challenging and complex task that requires significant time, which can take GPs to their limits. There is a great need to improve patient-and family-centered proactive communication, as well as interprofessional cooperation. Strengthening the team approach in primary care could relieve the burden on GPs, especially in rural areas, while simultaneously improving end-of-life care for their patients. PMID- 27255465 TI - Timing of beta oscillatory synchronization and temporal prediction of upcoming stimuli. AB - Modulations of beta oscillatory power serve a predictive role, in preparation of future actions. It is well known that beta amplitude decreases prior to voluntary movements and expected tactile stimuli. Paradoxically, recent studies have reported a beta amplitude increase prior to expected visual and auditory stimuli. Moreover, it has been suggested that, in isochronic stimulus series, the rising beta slope is adjusted to the duration of the interstimulus interval. We investigated the characteristics of such timing related pre-stimulus beta power increases using visual stimulus sequences that were presented at three regular rates (0.61, 0.74 and 0.95Hz). EEG was recorded from twenty participants while they attended the sequences by performing a clock reading task. Time-frequency analyses showed a consistent pattern of beta modulation: the post-stimulus beta power decrease was followed by a steep increase. Contrary to recent views, we found that the peaks of beta power, for the three presentation rates, were reached at a similar latency post-stimulus, instead of a fixed interval preceding the next stimulus. This demonstrates that, at interstimulus intervals between 1 2s, beta synchronization slopes are not modulated by timing mechanisms related to prediction of upcoming stimuli. We reconcile the discrepant results by proposing that when shorter interval durations are used, as in previous studies, beta resynchronization is interrupted by the presentation of a new stimulus, making it seem as if beta power peaks prior to upcoming stimuli. We emphasize caution with respect to the notion that the timing of beta synchronization is an expression of predictive timing. PMID- 27255466 TI - Low vaccination coverage for seasonal influenza and pneumococcal disease among adults at-risk and health care workers in Ireland, 2013: The key role of GPs in recommending vaccination. AB - The World Health Organization (WHO), and European Agencies recommend influenza vaccination for individuals at-risk due to age (>=65 years), underlying diseases, pregnancy and for health care workers (HCWs) in Europe. Pneumococcal vaccine is recommended for those at-risk of pneumococcal disease. In Ireland, vaccination uptake among at-risk adults is not routinely available. In 2013, we conducted a national survey among Irish residents >=18 years of age, to estimate size and vaccination coverage of at-risk groups, and identify predictive factors for influenza vaccination. We used computer assisted telephone interviews to collect self-reported information on health, vaccination status, attitudes towards vaccination. We calculated prevalence and prevalence ratios (PR) using binomial regression. Overall, 1770 individuals participated. For influenza, among those aged 18-64 years, 22% (325/1485) [95%CI: 17%-20%] were at-risk; 28% [95%CI: 23% 33%] were vaccinated. Among those aged >=65 years, 60% [95%CI: 54%-66%] were vaccinated. Influenza vaccine uptake among HCWs was 28% [95%CI: 21%-35%]. For pneumococcal disease, among those aged 18-64 years, 18% [95%CI: 16%-20%] were at risk; 16% [95%CI: 12%-21%] reported ever-vaccination; among those aged >=65 years, 36% [95%CI: 30%-42%] reported ever-vaccination. Main reasons for not receiving influenza vaccine were perceptions of not being at-risk, or not thinking of it; and among HCWs thinking that vaccination was not necessary or they were not at-risk. At-risk individuals were more likely to be vaccinated if their doctor had recommended it (PR 3.2; [95%CI: 2.4%-4.4%]) or they had access to free medical care or free vaccination services (PR 2.0; [95%CI: 1.5%-2.8%]). Vaccination coverage for both influenza and pneumococcal vaccines in at-risk individuals aged 18-64 years was very low. Influenza vaccination coverage among individuals >=65 years was moderate. Influenza vaccination status was associated with GP vaccination recommendation and free access to vaccination services. Doctors should identify and recommend vaccination to at-risk patients to improve uptake. PMID- 27255467 TI - Pigment patterns and photoprotection of anthocyanins in the young leaves of four dominant subtropical forest tree species in two successional stages under contrasting light conditions. AB - Light-driven subtropical forest succession is a dynamic process in which mesophytic climax communities replace heliophytic ones. Juvenile leaves (particularly mesophytic ones) are sensitive to high irradiances. To determine the photoprotection strategy that juvenile leaves use during subtropical forest succession, anthocyanin accumulation patterns were investigated in the young leaves of two mid-successional dominant trees (i.e., Schima superba and Castanopsis fissa) and two late-successional dominant trees (i.e., Cryptocarya concinna and Acmena acuminatissima) grown in 100% (FL) and 25% (LL) of full sunlight. All four tree species produced anthocyanins in their juvenile leaves when <50% of chlorophylls and carotenoids had developed. Higher anthocyanin concentrations accumulated in the young leaves grown in FL than in those grown in LL and in late-successional than in mid-successional trees. The juvenile leaves of late-successional trees were subjected to higher light-induced photoinhibition than those of mid-successional trees, despite of the fact that the leaves of late successional trees showed greater non-photochemical quenching than those of mid successional trees. Under LL conditions, photosystem II excitation pressure (1 - qP) was significantly higher in the juvenile leaves of late-successional trees than those of mid-successional trees. Under either FL or LL conditions, anthocyanin concentrations in juvenile leaves were negatively related to the light compensation point in mature leaves across species. However, anthocyanin concentrations were positively related to the antioxidant capacity of juvenile leaves. These results indicate that anthocyanin accumulation in the juvenile leaves of subtropical dominant trees during forest community succession is a flexible photoprotective response to ambient irradiances according to leaf sensitivity to light. PMID- 27255470 TI - Acidemia in neonates with a 5-minute Apgar score of 7 or greater - What are the outcomes? AB - BACKGROUND: The Apgar score is universally used for fetal assessment at the time of birth, whereas, the collection of fetal cord blood gases is performed commonly in high-risk situations or in the setting of Apgar scores of <7, which is a less standardized approach. It has been well-established that neonatal acidemia at the time of delivery can result in significant neonatal morbidity and death. Because of this association, knowledge of the fetal acid-base status and detection of acidemia at the time of delivery can serve as a sensitive and useful component in the assessment of a neonate's risk. Umbilical cord blood gas analysis is an accurate and validated tool for the assessment of neonatal acidemia at the time of delivery. Because the collection of fetal cord blood gases is not a standardized practice, it is possible that, with such a varied approach, some cases of neonatal acidemia are not detected, particularly in the setting of reassuring Apgar scores. OBJECTIVE: In a setting of universally obtained cord blood gases, we sought to identify the rates of acidemia and associated factors in neonates with 5-minute Apgar scores of >=7. STUDY DESIGN: This retrospective cohort study identified all term, singleton, nonanomolous neonates with 5-minute Apgar scores of >=7. The incidence of umbilical artery pH <=7.0 or <=7.1 and base excess <=-12 mmol/L or <=-10 mmol/L were examined overall and in association with obstetric complications and adverse neonatal outcomes. Chi-squared tests were used to compare proportions, and multivariable logistic regression was used to control for potential confounders. RESULTS: In this cohort, the incidence of an umbilical artery pH of <=7.0 was 0.5%, of a pH <=7.1 was 3.4%, of a base excess <=-12 mmol/L was 1.4%, and of <=-10 mmol/L was 4.0%. Rates of neonatal acidemia were greater in the setting of meconium (4.3% vs 3.2%; P<.001), placental abruption (13.2% vs 3.4%; P<.001), and cesarean deliveries (5.8% vs 2.8%; P<.001), despite normal 5-minute Apgar scores. Additionally, umbilical artery pH <=7.0 was associated with an increased risk of respiratory distress syndrome (adjusted odds ratio, 6.5; 95% confidence interval, 2.9-14.3) and neonatal intensive care unit admission (adjusted odds ratio, 10.8; 95% confidence interval, 6.8-17.4). Base excess of <=-12 mmol/L was also associated with an increased risk of neonatal sepsis (adjusted odds ratio, 4.7; 95% confidence interval, 1.9-12.1). Finally, when examined together, neonates with both a pH of <=7.0 and base excess of <=-12 mmol/L continued to demonstrate an increased risk of neonatal intensive care unit admission and respiratory distress syndrome, with adjusted odds ratios of 9.6 and 6.0, respectively. This risk persisted in neonates with a pH of <=7.1 and base excess of <=-10 mmol/L as well, with adjusted odds ratios of 4.5 and 1.1, respectively. CONCLUSION: Because neonates with reassuring Apgar scores have a residual risk of neonatal acidemia that is associated with higher rates of adverse outcomes, the potential utility of obtaining universal cord blood gases should be further investigated. PMID- 27255469 TI - The Bone Microenvironment: a Fertile Soil for Tumor Growth. AB - Bone metastatic disease remains a significant and frequent problem for cancer patients that can lead to increased morbidity and mortality. Unfortunately, despite decades of research, bone metastases remain incurable. Current studies have demonstrated that many properties and cell types within the bone and bone marrow microenvironment contribute to tumor-induced bone disease. Furthermore, they have pointed to the importance of understanding how tumor cells interact with their microenvironment in order to help improve both the development of new therapeutics and the prediction of response to therapy. PMID- 27255471 TI - Pregnant at work: time for prenatal care providers to act. AB - Fifty years ago, when a woman became pregnant, she was expected to stop working. Today, however, most women who work are the primary, sole, or co-breadwinner for their families, and their earnings during pregnancy are often essential to their families' economic well-being. Medical data about working during pregnancy are sparse but generally show that both low-risk and high-risk women can tolerate work-related duties well, although some work accommodations (eg, providing a chair for sitting, allowing snacks, or modifying the work schedule) may be necessary. However, some employers refuse to accommodate pregnant women who need adjustments. This can result in a woman being forced to make the choice between working without accommodations and losing her income and health insurance or even her job. Prenatal care providers can play an important role by implementing changes in their own practice, shaping public policy, and conducting research to increase protections for pregnant women and to ensure that they receive medically recommended accommodations while continuing to earn income for their growing families. PMID- 27255468 TI - Novel insights into redox system and the mechanism of redox regulation. AB - In view of the critical role of redox system in numerous physiological and pathophysiological processes, it is important to clearly understand the family members and regulatory mechanism of redox system. In this work, we will systematically review the current data detailing the reactive oxygen species (ROS), enzymatic and non-enzymatic antioxidants and redox sensitive transcription factors and we give a brief description of redox-mediated epigenetic and post translational regulation. We propose that the redox system functions as a "Redox Chain", consisting of "ROS-generating Enzyme Chain", "Combined Antioxidant Chain" and "Transcription Factor Chain". We suggest that an individualized assessment of the redox status in the body should be conducted for the redox intervention of a patient. The strategy of intervention is to maintain redox homeostasis via either facilitation of ROS signaling or enhancement of antioxidant defense. These findings provide valuable new insights into redox system and open up new paths for the control of redox-related disorders. PMID- 27255472 TI - The effect of combined inositol supplementation on maternal metabolic profile in pregnancies complicated by metabolic syndrome and obesity. AB - BACKGROUND: Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype. OBJECTIVE: The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model. STUDY DESIGN: Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice. RESULTS: Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 +/- 3984.4 vs placebo: 29687.14 +/- 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 +/- 976.4 pg/dL vs placebo: 24181.9 +/- 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D chiroinositol-treated dams compared with the placebo group (myoinositol/D chiroinositol: 10.9 +/- 0.5 g vs 12.6 +/- 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity. CONCLUSION: Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams. PMID- 27255473 TI - Association of interleukin-2 and interferon-gamma single nucleotide polymorphisms with Juvenile systemic lupus erythematosus. AB - PURPOSE: Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon gamma (IFN-gamma) genes in a case control study. MATERIALS AND METHODS: The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at -330, rs2069762, and G/T at +166, rs2069763) and IFN-gamma (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. RESULTS: Results of the analysed data revealed a negative allelic association for JSLE in IL-2 -330/T (P=0.02), as well as a positive allelic association for IL-2 330/G (P=0.02). IL-2 GG genotype (-330) in the patient group was also significantly overrepresented (P<0.001), while IL-2 GT genotype (-330) was notably decreased in the patients with JSLE (P<0.001). Additionally, the frequency of IL-2 (-330, +166) GT haplotype was significantly higher in the patient group (P<0.001). CONCLUSION: IL-2 cytokine gene polymorphisms could affect individual susceptibility to JSLE and can take on the role of possible genetic markers for vulnerability to JSLE. PMID- 27255474 TI - Effects of zinc supplementation in the prevention of respiratory tract infections and diarrheal disease in Colombian children: A 12-month randomised controlled trial. AB - BACKGROUND: Among the preventive strategies for lowering the incidence of upper respiratory tract infections (URTI) and acute diarrhoea episodes, two of the most common diseases in children, zinc supplementation has received special interest. However, there is a need for additional studies that determine the preventive effects of different doses of zinc on URTI and diarrhoeal disease episodes in children. METHODS: In a randomised, triple-blind clinical trial, we evaluated the efficacy of 12 months of daily zinc supplementation in the incidence of URTI and acute diarrhoea in a population of healthy children aged between 6 and 12 months living in Bogota, Colombia. The outcomes analysed were incidence of URTI, acute diarrhoeal disease episodes, and side effects of the interventions. RESULTS: Between 2010 and 2013, a total of 355 children underwent randomisation, with 174 assigned to the zinc supplementation group and 181 to the control group. In the multivariate analyses, having been randomised to the non-supplemented control group (IRR 1.73, 95% CI 1.52-1.97, p<0.001), and nursery attendance (IRR 1.41, 95% CI 1.07-1.87, p=0.016) were independently linked to the number of URTI. Likewise, having been randomised to the non-supplemented group (IRR 1.43, 95% CI 1.20-1.71, p<0.001), and lower socioeconomic status (IRR 1.86, 95% CI 1.11-3.13, p=0.018) were independently associated to the number of diarrhoeal disease episodes. CONCLUSIONS: Daily supplementation of 5mg of zinc during 12 months significantly decreased the incidence of URTI and diarrhoeal disease episodes in a healthy population of children aged between 6 and 12 months. PMID- 27255475 TI - Mould and grass pollen allergy as risk factors for childhood asthma in Zaragoza, Spain. AB - OBJECTIVE: Examine the prevalence of asthma and associated predictive factors in a group of 468 students. PATIENTS AND METHODS: A descriptive, cross-sectional observational study in a randomly selected population of 468 children aged 10-12, in the city of Zaragoza. We used the ISAAC questionnaire on asthma completed by children under supervision of the investigators. We assessed the genetic risk (family history of asthma) and environmental risks. The risk for atopy was assessed by the presence of positive skin prick tests. RESULTS: 25.3% of the children had symptoms consistent with asthma in the city of Zaragoza. Among them 33.1% reported a history of asthma in close relatives (OR=1.78, p<0.001). The history of hospitalisations for lower respiratory tract illness was strongly associated with the presence of asthma (OR=6.72, p<0.0001). Positive skin tests to Alternaria (OR=2.00, p<0.0001) and grass pollen (OR=1.76, p<0.001) were predictors of asthma. 63.6% of asthmatic children had presented clinical rhinitis in the previous 12 months, compared with 32% of non-asthmatics, and this difference was statistically significant (OR=3.89, p<0.0001). 47% of asthmatics presented with or previously had eczema, whereas only 26.9% of non-asthmatics presented with or previously had these types of lesions (p<0.0001). CONCLUSION: The following are predictors of asthma: History of hospital admissions for lower respiratory tract illness, presence of rhinitis and/or eczema, positive prick test for certain aeroallergens, especially Alternaria and grass pollen, and family history of asthma. PMID- 27255476 TI - Response to pneumococcal polysaccharide vaccine in children with asthma, and children with recurrent respiratory infections, and healthy children. AB - BACKGROUND: To analyse specific immune response to the 23-valent pneumococcal polysaccharide vaccine by measuring pneumococcal antibodies in children with asthma and with respiratory recurrent infection (RRI) as compared to healthy children. METHODS: The study included 60 children, divided into three groups: 20 with asthma, 20 with RRI, and 20 healthy controls. Post-vaccination specific IgG antibodies against 10 pneumococcal serotypes (S1, S3, S4, S5, S6B, S9V, S14, S18C, S19F, and S23F) contained in the 23-valent pneumococcal polysaccharide vaccine (PPV) were measured. A specific IgG concentration >=1.3MUg/mL was considered a protective response to the vaccine. For statistical analysis, levels of specific IgG antibodies against each of the 10 pneumococcal serotypes were compared across the three groups of children using the x(2) test. RESULTS: All of the children showed antipneumococcal antibody levels >1.3MUg/mL for over 70% of the serotypes, considered within the normal range of response. Average IgG antibody levels and percentages of children protected were statistically comparable among the three groups studied. CONCLUSION: The asthmatic children without RRI had pneumococcal antibody levels and percentages of serotype-specific protection to PPV comparable to those of healthy children. Asthmatic children with recurrent infections should be evaluated for specific antibody deficiency (SAD). Because asthma patients are at high risk for invasive pneumococcal infections, it would be worthwhile to explore systematic administration of PPV in children over the age of two years who have not received a pneumococcal conjugate vaccine, considering the positive response to PPV reported here. PMID- 27255477 TI - Association between two polymorphisms of histamine-metabolising enzymes and the severity of allergic rhinitis in a group of Mexican children. AB - BACKGROUND: It has been suggested that polymorphisms of histamine metabolising enzymes can be a risk factor for developing histamine-involving diseases. The aim of the present study is to research the possible association between two functional single nucleotide polymorphisms (SNPs): C314T in the Histamine-N Methyl Transferase gene and C2029G in the Diamine Oxidase gene, with the severity of allergic rhinitis and the number of allergic diseases, in a group of allergic Mexican children. METHODS: We studied 154 unrelated allergic children. SNPs were analysed by RT-PCR. The total serum IgE was measured by chemiluminescence and the serum histamine by ELISA. We used logistic regression analysis to determine OR. RESULTS: Patients carrying the mutant allele for any SNP had more risk to develop higher rhinitis severity or a bigger number of allergic diseases. Haplotype analysis revealed that this effect is synergistic. In patients carrying one or two mutant alleles, serum histamine levels were higher than those of patients carrying only wild alleles. Serum IgE levels were not associated with the presence of mutant alleles. CONCLUSION: The presence of these SNPs in patients with allergic rhinitis can lead to higher serum histamine, therefore to a higher risk of developing more severe symptoms or more associated allergic diseases, even if the serum IgE remains low. PMID- 27255478 TI - Development of a solitary koinobiont hyperparasitoid in different instars of its primary and secondary hosts. AB - Parasitoid wasps are excellent organisms for studying the allocation of host resources to different fitness functions such as adult body mass and development time. Koinobiont parasitoids attack hosts that continue feeding and growing during parasitism, whereas idiobiont parasitoids attack non-growing host stages or paralyzed hosts. Many adult female koinobionts attack a broad range of host stages and are therefore faced with a different set of dynamic challenges compared with idiobionts, where host resources are largely static. Thus far studies on solitary koinobionts have been almost exclusively based on primary parasitoids, yet it is known that many of these are in turn attacked by both koinobiont and idiobiont hyperparasitoids. Here we compare parasitism and development of a primary koinobiont hyperparasitoid, Mesochorus gemellus (Hymenoptera: Ichneumonidae) in larvae of the gregarious primary koinobiont parasitoid, Cotesia glomerata (Hymenoptera: Braconidae) developing in the secondary herbivore host, Pieris brassicae (Lepidoptera: Pieridae). As far as we know this is the first study to examine development of a solitary primary hyperparasitoid in different stages of its secondary herbivore host. Pieris brassicae caterpillars were parasitized as L1 by C. glomerata and then these parasitized caterpillars were presented in separate cohorts to M. gemellus as L3, L4 or L5 instar P. brassicae. Different instars of the secondary hosts were used as proxies for different developmental stages of the primary host, C. glomerata. Larvae of C. glomerata in L5 P. brassicae were significantly longer than those in L3 and L4 caterpillars. Irrespective of secondary host instar, every parasitoid cluster was hyperparasitized by M. gemellus but all only produced male progeny. Male development time decreased with host stage attacked, whereas adult male body mass did not, which shows that M. gemellus is able to optimally exploit older host larvae in terms of adult size despite their decreasing mass during the pupal stage. Across a range of cocoon masses, hyperparasitoid adult male body mass was approximately 84% as large as primary parasitoids, revealing that M. gemellus is almost as efficient at exploiting host resources as secondary (pupal) hyperparasitoids. PMID- 27255479 TI - Prognostic value of preoperative NLR, dNLR, PLR and CRP in surgical renal cell carcinoma patients. AB - BACKGROUND: Emerging evidences indicate that inflammation plays a crucial role in carcinogenesis and tumor progression. Inflammatory response biomarkers are recognized as promising prognostic factors for improving predictive accuracy in renal cell carcinoma (RCC). We aimed to evaluate the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR) and serum C-reactive protein (CRP) in RCC. METHODS: 484 surgical RCC patients were enrolled from 2006 to 2010 in this study. Receiver operating curve (ROC) was applied to assess the optimal cutoff levels for four biomarkers, and the prognostic values were determined by Kaplan-Meier curve, univariate and multivariate COX regression models. The predictive accuracy was evaluated by concordance index (c-index). RESULTS: The median follow-up duration after surgical resection was 36 months. The optimal cutoff levels were 2.78 for NLR, 2.05 for dNLR, 185 for PLR and 5.1 for CRP by ROC curves analysis. Elevated NLR, dNLR, PLR and CRP were significantly correlated with worse overall survival (OS). Multivariate analysis showed that elevated NLR was an independent risk factor for OS, and NLR was superior to dNLR, PLR and CRP based on hazard ratio (HR 2.10, 95 % CI 1.21-3.64, P = 0.008). Additionally, the nomogram could more effectively work in predicting OS (c-index: 0.749) in surgical RCC patients. CONCLUSION: Pre-operation NLR can be considered as a potential prognostic biomarker in patients with RCC who underwent surgical resection. PMID- 27255480 TI - Correlates of mobile screen media use among children aged 0-8: protocol for a systematic review. AB - BACKGROUND: Childhood is a crucial period for shaping healthy behaviours; however, it currently appears to be dominated by screen time. A large proportion of young children do not adhere to the screen time recommendations, with the use of mobile screen devices becoming more common than fixed screens. Existing systematic reviews on correlates of screen time have focused largely on the traditional fixed screen devices such as television. Reviews specially focused on mobile screen media are almost non-existent. This paper describes the protocol for conducting a systematic review of papers published between 2009 and 2015 to identify the correlates of mobile screen media use among children aged 0-8 years. METHODS: A systematic literature search of electronic databases will be carried out using different combinations of keywords for papers published in English between January 2009 and December 2015. Additionally, a manual search of reference lists and citations will also be conducted. Papers that have examined correlates of screen time among children aged 0-8 will be included in the review. Studies must include at least one type of mobile screen media (mobile phones, electronic tablets or handheld computers) to be eligible for inclusion. This study will identify correlates of mobile screen-viewing among children in five categories: (i) child biological and demographic correlates, (ii) behavioural correlates, (iii) family biological and demographic correlates, (iv) family structure-related correlates and (v) socio-cultural and environmental correlates. PRISMA statement will be used for ensuring transparency and scientific reporting of the results. DISCUSSION: This study will identify the correlates associated with increased mobile screen media use among young children through the systematic review of published peer-reviewed papers. This will contribute to addressing the knowledge gap in this area. The results will provide an evidence base to better understand correlates of mobile screen media use and potentially inform the development of recommendations to reduce screen time among those aged 0-8 years. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015028028 . PMID- 27255482 TI - A Simulation Framework for Benchmarking EEG-Based Brain Connectivity Estimation Methodologies. AB - Due to its high temporal resolution, electroencephalography (EEG) is widely used to study functional and effective brain connectivity. Yet, there is currently a mismatch between the vastness of studies conducted and the degree to which the employed analyses are theoretically understood and empirically validated. We here provide a simulation framework that enables researchers to test their analysis pipelines on realistic pseudo-EEG data. We construct a minimal example of brain interaction, which we propose as a benchmark for assessing a methodology's general eligibility for EEG-based connectivity estimation. We envision that this benchmark be extended in a collaborative effort to validate methods in more complex scenarios. Quantitative metrics are defined to assess a method's performance in terms of source localization, connectivity detection and directionality estimation. All data and code needed for generating pseudo-EEG data, conducting source reconstruction and connectivity estimation using baseline methods from the literature, evaluating performance metrics, as well as plotting results, are made publicly available. While this article covers only EEG modeling, we will also provide a magnetoencephalography version of our framework online. PMID- 27255481 TI - Purifying selection shapes the coincident SNP distribution of primate coding sequences. AB - Genome-wide analysis has observed an excess of coincident single nucleotide polymorphisms (coSNPs) at human-chimpanzee orthologous positions, and suggested that this is due to cryptic variation in the mutation rate. While this phenomenon primarily corresponds with non-coding coSNPs, the situation in coding sequences remains unclear. Here we calculate the observed-to-expected ratio of coSNPs (coSNPO/E) to estimate the prevalence of human-chimpanzee coSNPs, and show that the excess of coSNPs is also present in coding regions. Intriguingly, coSNPO/E is much higher at zero-fold than at nonzero-fold degenerate sites; such a difference is due to an elevation of coSNPO/E at zero-fold degenerate sites, rather than a reduction at nonzero-fold degenerate ones. These trends are independent of chimpanzee subpopulation, population size, or sequencing techniques; and hold in broad generality across primates. We find that this discrepancy cannot fully explained by sequence contexts, shared ancestral polymorphisms, SNP density, and recombination rate, and that coSNPO/E in coding sequences is significantly influenced by purifying selection. We also show that selection and mutation rate affect coSNPO/E independently, and coSNPs tend to be less damaging and more correlated with human diseases than non-coSNPs. These suggest that coSNPs may represent a "signature" during primate protein evolution. PMID- 27255483 TI - Effect of sitting postures and shoulder position on the cervicocephalic kinesthesia in healthy young males. AB - Information about head orientation, position, and movement with respect to the trunk relies on the visual, vestibular, extensive muscular, and articular proprioceptive system of the neck. Various factors can affect proprioception since it is the function of afferent integration, and tuning of muscular and articular receptors. Pain, muscle fatigue, and joint position have been shown to affect proprioceptive capacity. Thus, it can be speculated that changes in body posture can alter the neck proprioception. This study was undertaken to investigate the effect of body posture on cervicocephalic kinesthetic sense in healthy subjects. Cervicocephalic kinesthetic sensibility was measured by the kinesthetic sensibility test in healthy young adults while in (a) habitual slouched sitting position with arms hanging by the side (SS), (b) habitual slouched sitting position with arms unloaded (supported) (SS-AS), and (c) upright sitting position with arms hanging by the side (US) during maximum and 30 degree right, left rotations, flexion, and extension. Thirty healthy male adults (mean age 27.83; SD 3.41) volunteered for this study. The least mean error was found for the SS-AS position (0.48; SD 0.24), followed by SS (0.60; SD 0.43) and US (0.96; SD 0.71), respectively. For all test conditions, there was significant difference in mean absolute error while head repositioning from maximum and 30 degree rotation during SS and SS-AS positions (p < 0.05). In conclusion, body posture can affect the proprioception function of the neck. Supporting the upper extremities in such a way that their weight is unloaded, which leads to reduction in the tension between the neck and shoulder girdle, can improve cervicocephalic kinesthetic sense in both the horizontal and vertical planes. The findings of this study can be implemented in people who have to do repeated arm and neck movements, by using ergonomically effective chairs with proper arm supports. This might help in prevention and treatment of neck pain. PMID- 27255484 TI - The ERF11 Transcription Factor Promotes Internode Elongation by Activating Gibberellin Biosynthesis and Signaling. AB - The phytohormone gibberellin (GA) plays a key role in promoting stem elongation in plants. Previous studies show that GA activates its signaling pathway by inducing rapid degradation of DELLA proteins, GA signaling repressors. Using an activation-tagging screen in a reduced-GA mutant ga1-6 background, we identified AtERF11 to be a novel positive regulator of both GA biosynthesis and GA signaling for internode elongation. Overexpression of AtERF11 partially rescued the dwarf phenotype of ga1-6 AtERF11 is a member of the ERF (ETHYLENE RESPONSE FACTOR) subfamily VIII-B-1a of ERF/AP2 transcription factors in Arabidopsis (Arabidopsis thaliana). Overexpression of AtERF11 resulted in elevated bioactive GA levels by up-regulating expression of GA3ox1 and GA20ox genes. Hypocotyl elongation assays further showed that overexpression of AtERF11 conferred elevated GA response, whereas loss-of-function erf11 and erf11 erf4 mutants displayed reduced GA response. In addition, yeast two-hybrid, coimmunoprecipitation, and transient expression assays showed that AtERF11 enhances GA signaling by antagonizing the function of DELLA proteins via direct protein-protein interaction. Interestingly, AtERF11 overexpression also caused a reduction in the levels of another phytohormone ethylene in the growing stem, consistent with recent finding showing that AtERF11 represses transcription of ethylene biosynthesis ACS genes. The effect of AtERF11 on promoting GA biosynthesis gene expression is likely via its repressive function on ethylene biosynthesis. These results suggest that AtERF11 plays a dual role in promoting internode elongation by inhibiting ethylene biosynthesis and activating GA biosynthesis and signaling pathways. PMID- 27255485 TI - Redox- and Reactive Oxygen Species-Dependent Signaling into and out of the Photosynthesizing Chloroplast. AB - Photosynthesis is a high-rate redox metabolic process that is subjected to rapid changes in input parameters, particularly light. Rapid transients of photon capture, electron fluxes, and redox potentials during photosynthesis cause reactive oxygen species (ROS) to be released, including singlet oxygen, superoxide anion radicals, and hydrogen peroxide. Thus, the photosynthesizing chloroplast functions as a conditional source of important redox and ROS information, which is exploited to tune processes both inside the chloroplast and, following retrograde release or processing, in the cytosol and nucleus. Analyses of mutants and comparative transcriptome profiling have led to the identification of these processes and associated players and have allowed the specificity and generality of response patterns to be defined. The release of ROS and oxidation products, envelope permeabilization (for larger molecules), and metabolic interference with mitochondria and peroxisomes produce an intricate ROS and redox signature, which controls acclimation processes. This photosynthesis related ROS and redox information feeds into various pathways (e.g. the mitogen activated protein kinase and OXI1 signaling pathways) and controls processes such as gene expression and translation. PMID- 27255487 TI - Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification. AB - INTRODUCTION: Spontaneous reports of suspected adverse drug reactions (ADRs) can be analyzed to yield additional drug safety evidence for the pediatric population. Signal detection algorithms (SDAs) are required for these analyses; however, the performance of SDAs in the pediatric population specifically is unknown. We tested the performance of two SDAs on pediatric data from the US FDA Adverse Event Reporting System (FAERS) and investigated the impact of age stratification and age adjustment on the performance of SDAs. METHODS: We tested the performance of two established SDAs: the proportional reporting ratio (PRR) and the empirical Bayes geometric mean (EBGM) on a pediatric dataset from FAERS (2004-2012). We compared the performance of the SDAs with a published pediatric specific reference set by calculating diagnostic test-related statistics, including the area under the curve (AUC) of receiver operating characteristics. Impact of age stratification and age-adjustment on the performance of the SDAs was assessed. Age adjustment was performed by pooling (Mantel-Hanszel) stratum specific estimates. RESULTS: A total of 115,674 pediatric reports (patients aged 0-18 years) comprising 893,587 drug-event combinations (DECs) were analysed. Crude values of the AUC were similar for both SDAs: 0.731 (PRR) and 0.745 (EBGM). Stratification unmasked four DECs, e.g., 'ibuprofen and thrombocytopenia'. Age adjustment did not improve performance. CONCLUSION: The performance of the two tested SDAs was similar in the pediatric population. Age adjustment does not improve performance and is therefore not recommended to be performed routinely. Stratification can reveal new associations, and therefore is recommended when either drug use is age-specific or when an age-specific risk is suspected. PMID- 27255488 TI - Genetic control and regulatory mechanisms of succinoglycan and curdlan biosynthesis in genus Agrobacterium. AB - Agrobacterium is a genus of gram-negative bacteria that can produce several typical exopolysaccharides with commercial uses in the food and pharmaceutical fields. In particular, succinoglycan and curdlan, due to their good quality in high yield, have been employed on an industrial scale comparatively early. Exopolysaccharide biosynthesis is a multiple-step process controlled by different functional genes, and various environmental factors cause changes in exopolysaccharide biosynthesis through regulatory mechanisms. In this mini review, we focus on the genetic control and regulatory mechanisms of succinoglycan and curdlan produced by Agrobacterium. Some key functional genes and regulatory mechanisms for exopolysaccharide biosynthesis are described, possessing a high potential for application in metabolic engineering to modify exopolysaccharide production and physicochemical properties. This review may contribute to the understanding of exopolysaccharide biosynthesis and exopolysaccharide modification by metabolic engineering methods in Agrobacterium. PMID- 27255486 TI - A Cotton Annexin Affects Fiber Elongation and Secondary Cell Wall Biosynthesis Associated with Ca2+ Influx, ROS Homeostasis, and Actin Filament Reorganization. AB - Annexins play pivotal roles in a variety of cellular processes as well as in fiber development; however, the functional mechanisms of their activities are unclear. Here, an annexin gene that is preferentially expressed in fibers, GhFAnnxA, was found to be significantly associated with various cotton (Gossypium hirsutum) fiber traits. Transgenic analysis demonstrated that GhFAnnxA affected cotton fiber elongation and was involved in secondary cell wall (SCW) biosynthesis. Functional studies demonstrated that GhFAnnxA may act as a Ca(2+) conductance regulator and that reactive oxygen species (ROS) produced by Rbohs in a Ca(2+)-dependent manner may determine fiber elongation caused by elevated intracellular turgor and cell wall loosening. However, excessive hydrogen peroxide (H2O2) inhibited cotton fiber elongation in vitro. We speculate that a positive feedback loop involving ROS and Ca(2+) is regulated by GhCDPK1 and regulates fiber cell elongation. Furthermore, the convergence of actin filaments is altered by their interaction with GhFAnnxA, and this also may contribute to fiber elongation. Moreover, GhFAnnxA may affect SCW biosynthesis through changes in cell wall components caused by an increase in H2O2 levels. These results not only provide new insights into the signaling pathways of GhFAnnxA in fiber development but also clarify the role of ROS in fiber development. PMID- 27255489 TI - Identification and characterization of a novel (+)-gamma-lactamase from Microbacterium hydrocarbonoxydans. AB - 2-Azabicyclo[2.2.1]hept-5-en-3-one (gamma-lactam) is an important precursor of many carbocyclic nucleoside analogs and pharmaceuticals. (-)-gamma-Lactam has attracted much attention because of its role as an intermediate of antiviral drugs such as abacavir and carbovir. (+)-gamma-Lactamase can be used for the kinetic resolution of gamma-lactam to obtain (-)-gamma-lactam. In this study, a novel (+)-gamma-lactamase (Mh33H4-5540) was discovered from the gene library of Microbacterium hydrocarbonoxydans based on a colorimetric high-throughput screening method and it could be used to enantioselectively catalyze the bioresolution of racemic gamma-lactam with high enantiomeric excess (ee) (>99 %) and yield (>49 %). An unexpected finding was that Mh33H4-5540 was unrelated to other known gamma-lactamases (5.7, 4.8, 7.2, and 5.4 % similarities in amino sequence with (+)-gamma-lactamase from Comamonas acidovorans, Bradyrhizobium japonicum, Aeropyrum pernix, and Sulfolobus solfataricus, respectively) but rather related to isochorismatases. The homolog analysis of Mh33H4-5540 revealed that it was similar in structure with bacterial isochorismatases (an isochorismatase from Pseudomonas putida (PDB number 4H17) and a putative isochorismatase from Oleispira antarctica (PDB number 3LQY)). Thus, Mh33H4-5540 represented another type of (+)-gamma-lactamase. Mh33H4-5540 was overexpressed in E. coli Rosetta (DE3), purified to homogeneity and functionally characterized. The enzyme displayed optimal activity at 25 degrees C and pH 8.0. The activity showed a 5.5-fold increase in the presence of 0.5 M Ni2+ or Co2+. Mh33H4-5540 displayed much higher (+)-gamma-lactamase activity than any other biochemically characterized (+)-gamma-lactamases. Overall, we discovered a novel (+)-gamma lactamase Mh33H4-5540 which displayed the highest activity. It could be a promising candidate of biocatalyst for industrial applications of highly valuable chiral pharmaceutical chemicals. PMID- 27255490 TI - Gold nanoparticle-based lateral flow biosensor for rapid visual detection of Leishmania-specific DNA amplification products. AB - Leishmaniasis is a disease, caused by Leishmania parasites, which infect humans and animals, posing a major social and economic burden worldwide. The need for accurate and sensitive disease diagnosis led to the widespread adoption of PCR amplification. Detection of the amplification products (i.e. gel electrophoresis) require time-consuming protocols performed by trained personnel, with high cost. Aim of the present study was the simplification of PCR product detection, using a nucleic acid lateral flow, combined with functionalized gold nanoparticles. Amplification reactions targeting kinetoplastid DNA of Leishmania spp were performed on canine blood samples and a positive signal was formed as a red test zone. The visual detection was completed in 20min. Extensive optimization enabled the detection of 100fmol of target DNA. Clinical samples of infected dog blood were analyzed with high specificity. Overall, the proposed lateral flow biosensor can be considered an appealing alternative platform for Leishmania-specific amplification products detection with low cost and attractive simplicity. PMID- 27255491 TI - Impact of Age at Diagnosis and Hypothalamic Involvement on Body Mass Index Z Score Change in Pediatric Brain Tumor Survivors. AB - BACKGROUND: Obesity risk is increased for pediatric central nervous system tumor survivors. Hypothalamic involvement (HI) by tumor or treatment increases the risk. In healthy children, body mass index (BMI) normally declines until adiposity rebound (AR). We hypothesized that HI and diagnosis before AR would lead to increased BMI at follow-up. METHODS: A chart review of 114 brain tumor survivors diagnosed between 2001-2011 at the Children's Hospital of Wisconsin extracted tumor location, treatment and BMI z-scores at diagnosis and 2-year follow-up. Children were categorized based on age at diagnosis relative to AR and presence/absence of HI. RESULTS: Children diagnosed pre-AR and post-AR with HI had higher BMI z-scores at 2-year follow-up (pre-AR: 1.6, post-AR: 1.3) than at diagnosis (0.5, 0.6). All groups without HI showed no increase in BMI z-score from diagnosis to 2-year follow-up (pre-AR: 0.7-0.6, during AR: 0.7-0.8, post-AR: 0.7-0.8). The pre-AR and during-AR cohorts with HI had a higher BMI z-score at 2 year follow-up relative to those without HI, while the post-AR group did not. CONCLUSION: Except for the post-AR group, patients with HI have increased BMI at 2 years after diagnosis compared to those without HI. Diagnosis pre-AR is associated with greater follow-up BMI z-score. PMID- 27255492 TI - Cyclophosphamide versus mycophenolate mofetil in scleroderma interstitial lung disease (SSc-ILD) as induction therapy: a single-centre, retrospective analysis. AB - BACKGROUND: Scleroderma is a systemic autoimmune disease characterized mainly by skin manifestations and involvement of various visceral organs, especially the lungs. Lung involvement is the leading cause of mortality in patients with scleroderma. There are data to suggest that cyclophosphamide (CYC) and mycophenolate mofetil (MMF) are effective in the management of scleroderma interstitial lung disease (SSc-ILD) but no head to head comparative data are available to date. METHODS: For the last 3 years, patients with SSc-ILD have been treated at our centre by protocol-based administration of intravenous CYC and MMF. Results of lung function tests (spirometry) were recorded at baseline, 3 months and 6 months in every patient. The clinical records of patients with systemic sclerosis and significant ILD, who were not previously exposed to any immunosuppressant and were treated with MMF OR CYC, were reviewed. The efficacy of treatment was assessed by the change in forced vital capacity on spirometry. RESULTS: Of the total 57 patients included in the analysis, 34 were treated with MMF and 23 were treated with CYC. Mean duration of illness was 4.19 +/- 2.82 years in the MMF and 6.04 +/- 5.96 years in the CYC group. After 6 months of therapy, FVC increased by 10.84 +/- 13.81 % in the CYC group and by 6.07 +/- 11.92 % in the MMF group. This improvement from baseline was statistically significant in both groups (P < 0.01). The improvement was comparable with no statistically significant differences between groups (P = 0.373). There were no major adverse events reported in either arm. CONCLUSION: Both MMF and CYC were equally effective in stabilizing lung function in patients with scleroderma and ILD. PMID- 27255493 TI - Cryptococcal meningitis in a tertiary hospital in Pretoria, mortality and risk factors - A retrospective cohort study. AB - Aim This retrospective cohort study analyzes the impact of possible risk factors on the survival chance of patients with cryptococcal meningitis. These factors include the patient's socio-economic background, age, gender, presenting symptoms, comorbidities, laboratory findings and, in particular, non-adherence versus adherence to therapy. Methods Data were collected from all adult patients admitted to Kalafong Hospital with laboratory confirmed cryptococcal meningitis over a period of 24 months. We analyzed the data by the presentation of descriptive summary statistics, logistic regression was used to assess factors which showed association between outcome of measure and factor. Furthermore, multivariable logistic regression analysis using all the factors that showed significant association in the cross tabulation was applied to determine which factors had an impact on the patients' mortality risk. Results A total of 87 patients were identified. All except one were HIV-positive, of which 55.2% were antiretroviral therapy naive. A history of previous tuberculosis was given by 25 patients (28.7%) and 49 (56.3%) were on tuberculosis treatment at admission or started during their hospital stay. In-hospital mortality was 31%. Statistical analysis showed that antiretroviral therapy naive patients had 9.9 (CI 95% 1.2 81.2, p < 0.0032) times greater odds of dying compared to those on antiretroviral therapy, with 17 from 48 patients (35.4%) dying compared with 1 out of 21 patients (4.8%) on treatment. Defaulters had 14.7 (CI 95% 1.6-131.6, p < 0.016) times greater odds of dying, with 9 from 18 patients dying (50%), compared to the non-defaulters. In addition, patients who presented with nausea and vomiting had a 6.3 (95% CI 1.7-23.1, p < 0.005) times greater odds of dying (18/47, 38.3%); this remained significant when adjusted for antiretroviral therapy naive patients and defaulters. Conclusion Cryptococcal meningitis is still a common opportunistic infection in people living with HIV/AIDS resulting in hospitalization and a high mortality. Defaulting antiretroviral therapy and presentation with nausea and vomiting were associated with a significantly increased mortality risk. PMID- 27255494 TI - Can exercise affect the course of inflammatory bowel disease? Experimental and clinical evidence. AB - The inflammatory bowel disease (IBD) consisting of Crohn's disease (CD) and ulcerative colitis (UC) are defined as idiopathic, chronic and relapsing intestinal disorders occurring in genetically predisposed individuals exposed to environmental risk factors such as diet and microbiome changes. Since conventional drug therapy is expensive and not fully efficient, there is a need for alternative remedies that can improve the outcome in patients suffering from IBD. Whether exercise, which has been proposed as adjunct therapy in IBD, can be beneficial in patients with IBD remains an intriguing question. In this review, we provide an overview of the effects of exercise on human IBD and experimental colitis in animal models that mimic human disease, although the information on exercise in human IBD are sparse and poorly understood. Moderate exercise can exert a beneficial ameliorating effect on IBD and improve the healing of experimental animal colitis due to the activity of protective myokines such as irisin released from working skeletal muscles. CD patients with higher levels of exercise were significantly less likely to develop active disease at six months. Moreover, voluntary exercise has been shown to exert a positive effect on IBD patients' mood, weight maintenance and osteoporosis. On the other hand, depending on its intensity and duration, exercise can evoke transient mild systemic inflammation and enhances pro-inflammatory cytokine release, thereby exacerbating the gastrointestinal symptoms. We discuss recent advances in the mechanism of voluntary and strenuous exercise affecting the outcome of IBD in patients and experimental animal models. PMID- 27255495 TI - Charles S Hirsch. PMID- 27255496 TI - BME staff are more likely to be bullied in most acute trusts, report finds. PMID- 27255497 TI - Effects of Playing a Serious Computer Game on Body Mass Index and Nutrition Knowledge in Women. AB - BACKGROUND: Obesity and weight gain is a critical public health concern. Serious digital games are gaining popularity in the context of health interventions. They use persuasive and fun design features to engage users in health-related behaviors in a non-game context. As a young field, research about effectiveness and acceptability of such games for weight loss is sparse. OBJECTIVE: The goal of this study was to evaluate real-world play patterns of SpaPlay and its impact on body mass index (BMI) and nutritional knowledge. SpaPlay is a computer game designed to help women adopt healthier dietary and exercise behaviors, developed based on Self-Determination theory and the Player Experience of Need Satisfaction (PENS) model. Progress in the game is tied to real-life activities (e.g., eating a healthy snack, taking a flight of stairs). METHODS: We recruited 47 women to partake in a within-subject 90-day longitudinal study, with assessments taken at baseline, 1-, 2-, and 3- months. Women were on average, 29.8 years old (+/-7.3), highly educated (80.9% had BA or higher), 39% non-White, baseline BMI 26.98 (+/ 5.6), who reported at least contemplating making changes in their diet and exercise routine based on the Stages of Change Model. We computed 9 indices from game utilization data to evaluate game play. We used general linear models to examine inter-individual differences between levels of play, and multilevel models to assess temporal changes in BMI and nutritional knowledge. RESULTS: Patterns of game play were mixed. Participants who reported being in the preparation or action stages of behavior change exhibited more days of play and more play regularity compared to those who were in the contemplation stage. Additionally, women who reported playing video games 1-2 hours per session demonstrated more sparse game play. Brief activities, such as one-time actions related to physical activity or healthy food, were preferred over activities that require a longer commitment (e.g., taking stairs every day for a week). BMI decreased significantly (P<.001) from baseline to 3-month follow-up, yielding a large effect size of 1.28. Nutritional knowledge increased significantly (P<.001) from first to third month follow-ups, with an effect size of .86. The degree of change in both outcomes was related to game play, baseline readiness to change, and the extent of video game play in general. CONCLUSIONS: This work demonstrates initial evidence of success for using a serious game as an intervention for health behavior change in real world settings. Our findings also highlight the need to understand not only game effectiveness but also inter-individual differences. Individualizing content and the intervention medium appears to be necessary for a more personalized and long-lasting impact. PMID- 27255500 TI - Erratum to: Far-infrared promotes burn wound healing by suppressing NLRP3 inflammasome caused by enhanced autophagy. PMID- 27255499 TI - Plerixafor improves the endothelial health balance. The effect of diabetes analysed by polychromatic flow cytometry. AB - BACKGROUND AND AIMS: Diabetes damages the endothelium and reduces the availability of bone marrow (BM)-derived endothelial progenitor cells (EPCs). The mobilization of hematopoietic stem cells (HSCs) and EPCs in response to G-CSF is impaired by diabetes, owing to CXCL12 dysregulation. We have previously shown that the CXCR4/CXCL12 disruptor plerixafor rescues HSC and EPC mobilization in diabetes. We herein explored the effects of plerixafor on HSCs, EPCs, and circulating endothelial cells (CECs) in patients with and without diabetes. METHODS: We re-analysed data gathered in the NCT02056210 trial, wherein patients with (n = 10) and without diabetes (n = 10) received plerixafor to test stem/progenitor cell mobilization. We applied a novel and very specific polychromatic flow cytometry (PFC) approach to identify and quantify HSCs, EPCs, and CECs. RESULTS: We found that 7-AAD(-)Syto16(+)CD34(+)CD45(dim) HSC levels determined by PFC strongly correlated to the traditional enumeration of CD34(+) cells, whereas 7-AAD(-)Syto16(+)CD34(+)CD45(neg)KDR(+) EPCs were unrelated to the traditional enumeration of CD34(+)KDR(+) cells. Using PFC, we confirmed that plerixafor induces rapid mobilization of HSCs and EPCs in both groups, with a marginally significant defect in patients with diabetes. Plerixafor reduced live (7-AAD(-)) and dead (7-AAD(+)) Syto16(+)CD34(bright)CD45(neg)CD146(+) CECs more in patients without than in those with diabetes. The EPC/CEC ratio, a measure of the vascular health balance, was increased by plerixafor, but less prominently in patients with that in those without diabetes. CONCLUSIONS: In addition to rescuing defective mobilization associated with diabetes, plerixafor improves the balance between EPCs and CECs, but the latter effect is blunted in patients with diabetes. PMID- 27255501 TI - Effect of aerobic exercise intensity on glycemic control in type 2 diabetes: a meta-analysis of head-to-head randomized trials. AB - AIMS: To conduct a meta-analysis of head-to-head trials comparing aerobic exercise training of different intensities on glycemic control in type 2 diabetes. METHODS: Databases, including MEDLINE and EMBASE, were searched up to January 2016. Randomized trials of at least 12 weeks in duration that compared two exercise interventions of different intensities were identified. Two reviewers independently extracted data from eligible trials. Using fixed effect model, weighted mean differences (WMD) between different exercise intensities were calculated for changes in glycated hemoglobin (HbA1c) and secondary outcomes, such as fasting glucose and fasting insulin. RESULTS: Eight studies with a total of 235 participants were eligible. The exercise interventions lasted from 12 weeks to 6 months. The prescribed exercise intensities varied among studies. Four studies utilized vigorous exercise intensities for short durations by performing interval training. Overall, higher-intensity exercise resulted in a greater reduction in HbA1c compared to lower-intensity exercise (WMD = -0.22 %; 95 % confidence interval [-0.38, -0.06]; or -2.4 mmol/mol [-4.15, -0.66], I (2) = 0). Adherence to exercise and proportion of dropouts did not differ within trials. No adverse events were reported in these small trials with selected inclusion criteria. CONCLUSIONS: Although our meta-analysis had a limited sample size, increasing exercise intensity safely accentuated reductions in HbA1c in some people with type 2 diabetes. Different approaches have been used to increase exercise intensity (i.e., some used interval training, whereas others used higher intensity continuous exercise). However, at this time, it is unclear which form, if any, leads to the most favorable results. PMID- 27255502 TI - Fetal MRI versus postnatal imaging in the MR-compatible incubator. AB - INTRODUCTION: One of the aims of fetal magnetic resonance imaging (MRI) is to avoid postnatal scanning. However, clinicians sometimes wish to have postnatal confirmation of prenatal findings. This study's purpose was to check whether there was indeed the added value of neonatal MRI performed in the MR-compatible incubator (INC) after fetal examination. MATERIALS AND METHODS: Material consists of 25 neonates (14 girls) who underwent prenatal and postnatal MRI in a 1.5 T scanner, the latter in INC. Mean time of prenatal MRI was 30th gestational week, of postnatal MRI-16th day of life. RESULTS: In 14 cases (56 %) postnatal findings were the same as prenatal ones. In 11 (44 %) postnatal MRI showed some different/new/more precise results, in two the differences were attributed to other factors than the advantage of postnatal MRI over prenatal one. Altogether then postnatal results were partly discordant with prenatal ones in 9/25 cases (36 %). CONCLUSIONS: In most cases there was no added value of postnatal MRI as compared to prenatal one. This value lied in small details that could not have been noticed on prenatal MRI or required contrast medium administration to be noticed. On the other hand, MR examination performed with use of the dedicated neonatal coils in the MR-compatible incubator is a safe and reliable method of visualization of these small details with better spatial resolution thus helping to establish final diagnosis, treatment plan and prognosis. PMID- 27255503 TI - Radiotherapy in the multidisciplinary treatment of liver cancer: a survey on behalf of the Italian Association of Radiation Oncology. AB - PURPOSE: To report the results of the first Italian survey investigating the role of liver-directed radiotherapy in the multidisciplinary approach of primary and metastatic liver cancer. MATERIALS AND METHODS: A 21-item, two-section questionnaire was sent to all Italian radiotherapy centers on June 2014. The two sections aimed at: (1) evaluating the presence of a multidisciplinary liver tumor board and describing the role of radiation oncologists within the latter, (2) analyzing Radiotherapy treatment details and differences between centers. RESULTS: A total of 37 centers completed the survey. A multidisciplinary liver tumor board was available in most centers (73 %), with a radiation oncologist routinely attending the latter in the majority of cases (85 %). Most of the respondents considered liver-directed Radiotherapy as the third line choice when other therapies were not indicated or technically suitable. 18 centers reported the use of liver-directed radiotherapy. The majority of centers started liver irradiation after 2010. The most adopted motion management strategy was abdominal compression. The most adopted GTV-CTV expansion was 0 and 5 mm for metastases and hepatocellular carcinoma, respectively. Stereotactic body radiotherapy was the technique of choice; several treatment schedules were registered, being 45 Gy in three fractions the most reported fractionation scheme. Dose was prescribed at the PTV margin in most cases. CONCLUSION: Liver-directed radiotherapy represents a new field of interest which is currently adopted by 10 % of all Italian Centers. The technical equipment seems adequate. The variations observed in the treatment regimens reflect the lack of a well-established standard schedule. PMID- 27255504 TI - Sustained effectiveness of a multifaceted intervention to reduce potentially inappropriate prescribing in older patients in primary care (OPTI-SCRIPT study). AB - BACKGROUND: Potentially inappropriate prescribing (PIP) is common in older people in primary care and can result in increased morbidity, adverse drug events and hospitalisations. We previously demonstrated the success of a multifaceted intervention in decreasing PIP in primary care in a cluster randomised controlled trial (RCT). OBJECTIVE: We sought to determine whether the improvement in PIP in the short term was sustained at 1-year follow-up. METHODS: A cluster RCT was conducted with 21 GP practices and 196 patients (aged >=70) with PIP in Irish primary care. Intervention participants received a complex multifaceted intervention incorporating academic detailing, medicine review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices delivered usual care and received simple, patient-level PIP feedback. Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions at 1-year follow-up. Intention-to-treat analysis using random effects regression was used. RESULTS: All 21 GP practices and 186 (95 %) patients were followed up. We found that at 1-year follow-up, the significant reduction in the odds of PIP exposure achieved during the intervention was sustained after its discontinuation (adjusted OR 0.28, 95 % CI 0.11 to 0.76, P = 0.01). Intervention participants had significantly lower odds of having a potentially inappropriate proton pump inhibitor compared to controls (adjusted OR 0.40, 95 % CI 0.17 to 0.94, P = 0.04). CONCLUSION: The significant reduction in the odds of PIP achieved during the intervention was sustained after its discontinuation. These results indicate that improvements in prescribing quality can be maintained over time. TRIAL REGISTRATION: Current controlled trials ISRCTN41694007 . PMID- 27255505 TI - Combined assessment of clinical and patient factors on doctors' decisions to prescribe antibiotics. AB - BACKGROUND: Antibiotic overprescription is a worldwide problem. Decisions regarding antibiotic prescription for respiratory tract infections (RTIs) are influenced by medical and non-medical factors. METHODS: In family medicine practices in Bialystok, Poland, family medicine residents directly observed consultations with patients with RTI symptoms. The observing residents completed a questionnaire including patient data, clinical symptoms, diagnosis, any prescribed antibiotic, and assessment of ten patient pressure factors. RESULTS: Of 1546 consultations of patients with RTIs, 54.26 % resulted in antibiotic prescription. Antibiotic prescription was strongly associated with rales (OR 26.90, 95 % CI 9.00-80.40), tonsillar exudates (OR 13.03, 95 % CI 7.10-23.80), and wheezing (OR 14.72, 95 % CI 7.70-28.10). The likelihood of antibiotic prescription was increased by a >7-day disease duration (OR 3.94, 95 % CI 2.80 5.50), purulent nasal discharge (OR 3.87, 95 % CI 2.40-6.10), starting self medication with antibiotics (OR 4.11, 95 % CI 2.30-7.30), and direct request for antibiotics (OR 1.87, 95 % CI 1.30-2.80). Direct request not to prescribe antibiotics decreased the likelihood of receiving antibiotics (OR 0.34, 95 % CI 0.27-0.55). CONCLUSION: While clinical signs and symptoms principally impact prescribing decisions, patient factors also contribute. The most influential patient pressure factors were starting self-medication with antibiotics, and directly requesting antibiotic prescription or no antibiotic prescription. Interventions aiming to improve clinical sign and symptom interpretation and to help doctors resist direct patient pressure could be beneficial for reducing unnecessary antibiotic prescribing. PMID- 27255507 TI - Family history of diabetes predisposes to cardiovascular disease among patients with type 2 diabetes: What is the nature of the association? PMID- 27255508 TI - Changing needs of heart failure patients and their families during the illness trajectory: A challenge for health care. PMID- 27255506 TI - Forearm muscle oxidative capacity index predicts sport rock-climbing performance. AB - Rock-climbing performance is largely dependent on the endurance of the forearm flexors. Recently, it was reported that forearm flexor endurance in elite climbers is independent of the ability to regulate conduit artery (brachial) blood flow, suggesting that endurance is not primarily dependent on the ability of the brachial artery to deliver oxygen, but rather the ability of the muscle to perfuse and use oxygen, i.e., skeletal muscle oxidative capacity. PURPOSE: The aim of the study was to determine whether an index of oxidative capacity in the flexor digitorum profundus (FDP) predicts the best sport climbing red-point grade within the last 6 months. Participants consisted of 46 sport climbers with a range of abilities. METHODS: Using near-infrared spectroscopy, the oxidative capacity index of the FDP was assessed by calculating the half-time for tissue oxygen resaturation (O2HTR) following 3-5 min of ischemia. RESULTS: Linear regression, adjusted for age, sex, BMI, and training experience, revealed a 1-s decrease in O2HTR was associated with an increase in red-point grade by 0.65 (95 % CI 0.35-0.94, Adj R (2) = 0.53). CONCLUSIONS: Considering a grade of 0.4 separated the top four competitors in the 2015 International Federation Sport Climbing World Cup, this finding suggests that forearm flexor oxidative capacity index is an important determinant of rock-climbing performance. PMID- 27255509 TI - Nocardia shinanonensis sp. nov., isolated from a patient with endophthalmitis. AB - A nocardioform strain IFM 11456T was isolated from the aqueous humor from a patient with endophthalmitis and was characterized to its taxonomic position. IFM 11456T contained arabinose, galactose and meso-diaminopimelic acid in whole-cell hydrolysates and mycolic acids that co-migrated with those from the type strain of Nocardiaasteroides. The acyl type of muramic acid was N-glycolyl. The diagnostic polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and two unidentified glycolipids and the predominant menaquinone was MK-8(H4, omega cycl.). These characteristics are typical of members of the genus Nocardia. Results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the isolate represented a novel species of the genus Nocardia and was most closely related to the type strains of Nocardia mikamii JCM 15508T (98.1 %) and Nocardiaaobensis IFM 0372T (98.1 %). However, analysis of partial gyrB sequences showed that strain IFM 11456T had 90.2 % similarity to Nocardia concava IFM 0354T and 90 % to Nocardianiigatensis IFM 0330T. The DNA-DNA relatedness values for strain IFM 11456T compared with N. mikamii JCM 15508T, N. aobensisIFM 0372T and N. concava IFM 0354T ranged from 24.4 to 39.9 %. Phenotypic characteristics that differentiated IFM 11456T from phylogenetically related species were growth at 45 degrees C, utilization of citrate and growth with inositol as a sole carbon source. On the basis of this polyphasic study, the isolate represents a novel species within the genus Nocardia, for which the name Nocardia shinanonensis sp. nov. is proposed. The type strain is IFM 11456T (=NBRC 109590T=TBRC 5149T). PMID- 27255510 TI - Impact of attenuation correction on clinical [(18)F]FDG brain PET in combined PET/MRI. AB - BACKGROUND: In PET/MRI, linear photon attenuation coefficients for attenuation correction (AC) cannot be directly derived, and cortical bone is, so far, usually not considered. This results in an underestimation of the average PET signal in PET/MRI. Recently introduced MR-AC methods predicting bone information from anatomic MRI or proton density-weighted zero-time imaging may solve this problem in the future. However, there is an ongoing debate if the current error is acceptable for clinical use and/or research. METHODS: We examined this feature for [(18)F] fluorodeoxyglucose (FDG) brain PET in 13 patients with clinical signs of dementia or movement disorders who subsequently underwent PET/CT and PET/MRI on the same day. Multiple MR-AC approaches including a CT-derived AC were applied. RESULTS: The resulting PET data was compared to the CT-derived standard regarding the quantification error and its clinical impact. On a quantitative level, -11.9 to +2 % deviations from the CT-AC standard were found. These deviations, however, did not translate into a systematic diagnostic error. This, as overall patterns of hypometabolism (which are decisive for clinical diagnostics), remained largely unchanged. CONCLUSIONS: Despite a quantitative error by the omission of bone in MR-AC, clinical quality of brain [(18)F]FDG is not relevantly affected. Thus, brain [(18)F]FDG PET can already, even now with suboptimal MR-AC, be utilized for clinical routine purposes, even though the MR AC warrants improvement. PMID- 27255511 TI - The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic. AB - BACKGROUND: To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value. METHODS: Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose. RESULTS: The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge. CONCLUSIONS: This study shows that component resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group. PMID- 27255512 TI - Rice panicle plasticity in Near Isogenic Lines carrying a QTL for larger panicle is genotype and environment dependent. AB - BACKGROUND: Panicle architectural traits in rice (branching, rachis length, spikelet number) are established between panicle initiation and heading stages. They vary among genotypes and are prone to Genotype x Environment interactions. Together with panicle number, panicle architecture determines sink-based yield potential. Numerous studies analyzed genetic and environmental variation of plant morphology, but the plasticity of panicle structure is less well understood. This study addressed the response of rice panicle size and structure to limited light availability at plant level for near-isogenic lines (NILs) with IR64 or IRRI146 backgrounds, carrying the QTL qTSN4 (syn. SPIKE) for large panicles. Full light and shading in the greenhouse and two population densities in the field were implemented. The image analysis tool P-TRAP was used to analyze the architecture of detached panicles. RESULTS: The qTSN4 increased total branch length, branching frequency and spikelet number per panicle in IRRI146 background in the field and greenhouse, and in IR64 background in the greenhouse, but not for IR64 in the field. In the field, however, qTSN4 reduced panicle number, neutralizing any potential yield gains from panicle size. Shading during panicle development reduced spikelet and branch number but qTSN4 mitigated partly this effect. Spikelet number over total branch length (spikelet density) was a stable allometry across genotypes and treatments with variation in spikelet number mainly due to the frequency of secondary branches. Spikelet number on the main tiller was correlated with stem growth rate during panicle development, indicating that effects on panicle size seemed related to resources available per tiller. CONCLUSIONS: The qTSN4 effects on panicle spikelet number appear as indirect and induced by upstream effects on pre-floral assimilate resources at tiller level, as they were (1) prone to G x E interactions, (2) non-specific with respect to panicle architectural traits, and (3) associated with pre-floral stem growth rate. PMID- 27255513 TI - Genome evolution in alpine oat-like grasses through homoploid hybridization and polyploidy. AB - Hybridization and polyploidization can radically impact genome organization from sequence level to chromosome structure. As a result, often in response to environmental change and species isolation, the development of novel traits can arise and will tend to result in the formation of homoploid or polyploid hybrid species. In this study we focus on evidence of hybridization and polyploidization by ascertaining the species parentage of the endemic alpine Helictotrichon parlatorei group. This group comprises five taxa; the diploids H. parlatorei, Helictotrichon setaceum subsp. setaceum and subsp. petzense, their putative hybrid Helictotrichon *krischae and the hexaploid Helictotrichon sempervirens. For molecular analyses, cloned nuclear Topoisomerase VI genes of H. sempervirens and H. *krischae were sequenced and compared with sequences of the diploids to estimate the evolutionary history in this group. In addition, detailed chromosome studies were carried out including fluorescence in situ hybridization (FISH) with 5S and 45S ribosomal and satellite DNA probes, and fluorochrome staining with chromomycin and DAPI. Two distinct types of Topoisomerase VI sequences were identified. One of them (SET) occurs in both subspecies of H. setaceum, the other (PAR) in H. parlatorei. Both types were found in H. *krischae and H. sempervirens Karyotypes of H. parlatorei and H. setaceum could be distinguished by chromosomes with a clearly differentiated banding pattern of ribosomal DNAs. Both patterns occurred in the hybrid H. *krischae Hexaploid H. sempervirens shares karyotype features with diploid H. parlatorei, but lacks the expected chromosome characteristics of H. setaceum, possibly an example of beginning diploidization after polyploidization. The geographic origin of the putative parental species and their hybrids and the possible biogeographical spread through the Alps are discussed. PMID- 27255514 TI - The structure of legume-rhizobium interaction networks and their response to tree invasions. AB - Establishing mutualistic interactions in novel environments is important for the successful establishment of some non-native plant species. These associations may, in turn, impact native species interaction networks as non-natives become dominant in their new environments. Using phylogenetic and ecological interaction network approaches we provide the first report of the structure of belowground legume-rhizobium interaction networks and how they change along a gradient of invasion (uninvaded, semi invaded and heavily invaded sites) by Australian Acacia species in South Africa's Cape Floristic Region. We found that native and invasive legumes interact with distinct rhizobial lineages, most likely due to phylogenetic uniqueness of native and invasive host plants. Moreover, legume rhizobium interaction networks are not nested, but significantly modular with high levels of specialization possibly as a result of legume-rhizobium co evolution. Although network topology remained constant across the invasion gradient, composition of bacterial communities associated with native legumes changed dramatically as acacias increasingly dominated the landscape. In stark contrast to aboveground interaction networks (e.g. pollination and seed dispersal) we show that invasive legumes do not infiltrate existing native legume rhizobium networks but rather form novel modules. This absence of mutualist overlap between native and invasive legumes suggests the importance of co invading rhizobium-acacia species complexes for Acacia invasion success, and argues against a ubiquitous role for the formation and evolutionary refinement of novel interactions. PMID- 27255515 TI - Variability in the amount of homoeologous pairing among F1 hybrids. AB - Genes involved in the exclusive pairing of homologous chromosomes have been described in several polyploid species but little is known about the activity of these genes in diploids (which have only one dose of each homoeologous genome). Analysis of the meiotic behaviour of species, natural and artificial hybrids and polyploids of Glandularia suggests that, in allopolyploids where homoeologous genomes are in two doses, regulator genes prevent homoeologous pairing. The different meiotic phenotypes in diploid F1 hybrids between Glandularia pulchella and Glandularia incisa strongly suggest that these pairing regulator genes possess an incomplete penetrance when homoeologous genomes are in only one dose. Moreover, the meiotic analysis of natural and artificial F1 hybrids suggests that the genetic constitution of parental species influences the activity of pairing regulator genes and is mainly responsible for variability in the amount of homoeologous pairing observed in diploid hybrids. In Glandularia, the pairing regulator genes originated in South American diploid species. The cytogenetic characteristics of this genus make it a good model to analyse and explore in greater depth the activity of pairing regulator genes at different ploidy levels. PMID- 27255516 TI - The use of plant community attributes to detect habitat quality in coastal environments. AB - The monitoring of biodiversity has mainly focused on the species level. However, researchers and land managers are making increasing use of complementary assessment tools that address higher levels of biological organization, i.e. communities, habitats and ecosystems. Recently, a variety of frameworks have been proposed for assessing the conservation status of communities or ecosystems. Among the various criteria proposed, all the protocols suggest considering (i) spatial aspects (range and area), and (ii) qualitative aspects of specific structures and functions. However, changes to ecological function are difficult to quantify and many protocols end up by using qualitative criteria. The aim of this work was to test the efficacy of some plant community attributes for the detection of vegetation quality in sand dune plant communities. We chose plant community attributes that either help to distinguish a habitat from others (diagnostic components) or play a significant role in habitat function and persistence over time. We used a diachronic approach by contrasting up-to-date vegetation data with data from previous studies carried out within the same areas. Changes in species composition were detected through detrended correspondence analyses (detrended correspondence analyses), Multi-Response Permutation Procedures and Indicator Species Analysis, while structural changes were analyzed by comparing species richness, total species cover, ecological groups of species and growth forms through null models. Ecological groups such as native focal species and aliens, and growth forms proved their efficacy in discriminating between habitat types and in describing their changes over time. The approach used in this study may provide an instrument for the assessment of plant community quality that can be applied to other coastal ecosystems. PMID- 27255517 TI - Neural Reactivity to Angry Faces Predicts Treatment Response in Pediatric Anxiety. AB - Although cognitive-behavioral psychotherapy (CBT) and pharmacotherapy are evidence-based treatments for pediatric anxiety, many youth with anxiety disorders fail to respond to these treatments. Given limitations of clinical measures in predicting treatment response, identifying neural predictors is timely. In this study, 35 anxious youth (ages 7-19 years) completed an emotional face-matching task during which the late positive potential (LPP), an event related potential (ERP) component that indexes sustained attention towards emotional stimuli, was measured. Following the ERP measurement, youth received CBT or selective serotonin reuptake inhibitor (SSRI) treatment, and the LPP was examined as a predictor of treatment response. Findings indicated that, accounting for pre-treatment anxiety severity, neural reactivity to emotional faces predicted anxiety severity post- CBT and SSRI treatment such that enhanced electrocortical response to angry faces was associated with better treatment response. An enhanced LPP to angry faces may predict treatment response insofar as it may reflect greater emotion dysregulation or less avoidance and/or enhanced engagement with environmental stimuli in general, including with treatment. PMID- 27255518 TI - Uncovering the composition of microbial community structure and metagenomics among three gut locations in pigs with distinct fatness. AB - Uncovering the phylogenetic composition of microbial community and the potential functional capacity of microbiome in different gut locations is of great importance to pig production. Here we performed a comparative analysis of gut microbiota and metagenomics among jejunum, ileum and cecum in pigs with distinct fatness. 16S rRNA gene sequencing revealed dramatic differences of microbial composition, diversity and species abundance between small intestine and cecum. Clostridium and SMB53 were enriched in the small intestine, while Prevotella, Treponema, Ruminococcus and Faecalibacterium showed a higher abundance in the cecum. Functional capacity analysis of gut microbiome revealed that the microbiome of small intestine plays important roles in the metabolism of small molecule nutrients, while the microbiome of cecum has the stronger ability to degrade xylan, pectin and cellulose. We identified tens of fatness associated bacterial species including Escherichia spp. that showed a notable increase of relative abundance in all three gut locations of high fatness pigs. We further suggested that the potential pathogens, inflammation process, and microbial metabolism and nutrient sensing are involved in the high fatness of pigs. These results improve our knowledge about microbiota compositions in different gut locations, and give an insight into the effect of gut microbiota on porcine fatness. PMID- 27255519 TI - Antiosteoporotic effect of Petroselinum crispum, Ocimum basilicum and Cichorium intybus L. in glucocorticoid-induced osteoporosis in rats. AB - BACKGROUND: Glucocorticoid-induced osteoporosis (GIO) is one of the serious side effects which have become the most common secondary osteoporosis. The purpose of this study is to evaluate the effect of aqueous extract of parsley, basil and chicory on glucocorticoid-induced osteoporosis in rats. METHODS: Fifty Female rats were divided into five groups and treated for 8 weeks as follow: group 1 served as control; group (2) subcutaneously injected with 0.1 mg/kg b. wt. dexamethasone dissolved in saline; group 3 received similar dose of dexamethasone together with aqueous parsley extract in a dose of 2 g/kg b. wt.; group 4 received similar dose of dexamethasone together with 400 mg/kg b. wt. aqueous basil extract and group 5 received similar dose of dexamethasone together with 100 mg/kg b. wt. aqueous chicory extract. RESULTS: The dexamethasone group showed a significant decrease in serum E2, Ca, P levels and significant decrease in total BMD, BMC and a significant increase in serum PTH, ALP and ACP. Bone TBARs was significantly increased while GSH, antioxidant enzymes were significantly decreased. These changes were attenuated by parsley, basil and chicory extracts in the group 3, 4 and 5 respectively. CONCLUSION: Aqueous extracts of parsley, basil and chicory showed bone protection against glucocorticoid-induced in rats. From our results, we concluded that chicory has a potent protective effect more than parsley and basil due to containing flavonoids and inulin. PMID- 27255520 TI - The Diagnosis of Metastatic Axillary Lymph Nodes of Breast Cancer By Diffusion Weighted Imaging: a meta-analysis and systematic review. AB - BACKGROUND: The purpose of this meta-analysis was to evaluate the clinical significance of diffusion-weighted imaging in assessing the status of axillary lymph nodes in patients with breast cancer. METHODS: We searched the PubMed, Cochrane, and EMBASE databases, selected studies by inclusion and exclusion criteria, and assessed the quality of selected studies. We explored the source of heterogeneity; calculated sensitivity, specificity, positive and negative likelihood ratios, and pretest probability. A summary receiver operating characteristic curve was performed. Student's t test was used to compare the different mean apparent diffusion coefficient values of different status lymph nodes. RESULTS: In selected 10 studies, a total of 801 patients and 2305 lymph nodes were included following inclusion criteria. All scores of the quality assessment of the included studies were greater than or equal to 10 points. The sensitivity was 0.89 (95 % CI 0.79-0.95), the specificity was 0.83 (95 % CI 0.71 0.91), the positive and negative likelihood ratios were 3.86 (95 % CI 2.75-5.41) and 0.17 (95 % CI 0.09-0.32), the pretest probabilities were 53 and 54 %, the area under the curve were 0.93 (95 % CI 0.90-0.95), respectively. The mean apparent diffusion coefficient value of metastatic lymph nodes was significantly lower than that of nonmetastatic axillary lymph nodes. CONCLUSIONS: Diffusion weighted imaging is a promising tool to discriminate between metastatic and nonmetastatic axillary lymph nodes. Combined with the mean apparent diffusion coefficient value, it can quantitatively diagnose lymph node metastases. Conducting large-scale, high-quality researches can improve the clinical significance of diffusion-weighted imaging to distinguish metastatic and nonmetastatic axillary lymph nodes in patients with breast cancer and provide the evidence to assess the status of axillary lymph nodes. PMID- 27255521 TI - Unique Case of Pseudomembranous Aspergillus Tracheobronchitis: Tracheal Perforation and Horner's Syndrome. AB - Pseudomembranous aspergillus tracheobronchitis is an uncommon form of invasive pulmonary aspergillosis, and it is generally seen in immunocompromised patients. We report about a mildly immunocompromised case with pseudomembranous aspergillus tracheobronchitis, which caused tracheal perforation, and Horner's syndrome. A 44 year-old female with uncontrolled diabetes mellitus, complaining of fever and dyspnea, was admitted to the hospital. She was hospitalized with community acquired pneumonia and diabetic ketoacidosis. Insulin infusion and empirical antibiotics were firstly commenced. Bronchoscopy showed left vocal cord paralysis with extensive whitish exudative membranes covering the trachea and the main bronchi. Liposomal amphotericin B was added due to the probability of fungal etiology. Mucosal biopsy revealed aspergillus species. Second bronchoscopic examination demonstrated a large perforation in the tracheobronchial system. Despite all treatments, respiratory failure developed on the 25th day and the patient died within 2 days. Pseudomembranous aspergillus tracheobronchitis is fatal in about 78 % of all cases despite appropriate therapy. Early diagnosis and efficient antifungal therapy may improve the prognosis. PMID- 27255524 TI - Mechanical and neural function of triceps surae in elite racewalking. AB - Racewalking is a unique event combining mechanical elements of walking with speeds associated with running. It is currently unclear how racewalking technique impacts lower limb muscle-tendon function despite the relevance of this to muscle economy and overall performance. The present study examined triceps surae neuromechanics in 11 internationally competitive racewalkers (age 25 +/- 11 yr) walking and running on a treadmill at speeds between 4.5 and 13.8 km/h while triceps surae fascicle lengths, electromyography, and kinematic data were recorded. Cumulative muscle activity required to traverse a unit distance (CMAPD) was calculated for each muscle. Medial gastrocnemius (MG) and soleus fascicle lengths/velocities were determined using an automated tracking algorithm, and muscle-tendon unit lengths were determined. Running was associated with net shortening of muscle fascicles during stance, combined with substantial lengthening of the muscle-tendon unit, implying energy storage in the Achilles tendon. When the same participants racewalked at the same speed, the fascicles shortened (soleus) or lengthened (MG), coinciding with rapid shortening followed by a relatively small increase in muscle-tendon length during stance. Consequently, compared with running at the same speed, racewalking decreased the energy-saving role of the Achilles tendon. Moreover, CMAPD was generally highest in racewalking, implying that in individual muscles, the energy cost of racewalking was higher than running. Together these results suggest that racewalking is neurally and mechanically costly relative to running at a given speed. As racewalking events are typically between 10 and 50 km, neuromechanical inefficiencies that occur with each stride likely result in substantial energetic penalties. PMID- 27255522 TI - Rapid Assays for Specific Detection of Fungi of Scopulariopsis and Microascus Genera and Scopulariopsis brevicaulis Species. AB - PURPOSE: Fungi of Scopulariopsis and Microascus genera cause a wide range of infections, with S. brevicaulis being the most prevalent aetiological agent of mould onychomycosis. Proper identification of these pathogens requires sporulating culture, which considerably delays the diagnosis. So far, sequencing of rDNA regions of clinical isolates has produced ambiguous results due to the lack of reference sequences in publicly available databases. Thus, there is a clear need for the development of new molecular methods that would provide simple, rapid and highly specific identification of Scopulariopsis and Microascus species. The objective of this study was to develop simple and fast assays based on PCR and real-time PCR for specific detection of fungi from Scopulariopsis and Microascus genera, and separately, S. brevicaulis species. METHODS: On the basis of alignment of beta-tubulin gene sequences, Microascus/Scopulariopsis-specific primers were designed and S. brevicaulis-specific primers were reevaluated. DNA from cultured fungal isolates, extracted in a two-step procedure, was used in Microascus/Scopulariopsis-specific and S. brevicaulis-specific PCR and real-time PCR followed by electrophoresis or melting temperature analysis, respectively. RESULTS: The specificity of the assays was confirmed, as positive results were obtained only for Scopulariopsis spp. and Microascus spp. isolates tested in Microascus/Scopulariopsis-specific assay, and only for S. brevicaulis and S. koningii (syn. S. brevicaulis) isolates in a S. brevicaulis-specific assay, respectively, and no positive results were obtained neither for other moulds, dermatophytes, yeast-like fungi, nor for human DNA. CONCLUSIONS: The developed assays enable fast and unambiguous identification of Microascus spp. and Scopulariopsis spp. pathogens. PMID- 27255523 TI - Effects of high-intensity interval training and moderate-intensity continuous training on endothelial function and cardiometabolic risk markers in obese adults. AB - We hypothesized that high-intensity interval training (HIIT) would be more effective than moderate-intensity continuous training (MICT) at improving endothelial function and maximum oxygen uptake (Vo2 max) in obese adults. Eighteen participants [35.1 +/- 8.1 (SD) yr; body mass index = 36.0 +/- 5.0 kg/m(2)] were randomized to 8 wk (3 sessions/wk) of either HIIT [10 * 1 min, 90 95% maximum heart rate (HRmax), 1-min active recovery] or MICT (30 min, 70-75% HRmax). Brachial artery flow-mediated dilation (FMD) increased after HIIT (5.13 +/- 2.80% vs. 8.98 +/- 2.86%, P = 0.02) but not after MICT (5.23 +/- 2.82% vs. 3.05 +/- 2.76%, P = 0.16). Resting artery diameter increased after MICT (3.68 +/- 0.58 mm vs. 3.86 +/- 0.58 mm, P = 0.02) but not after HIIT (4.04 +/- 0.70 mm vs. 4.09 +/- 0.70 mm; P = 0.63). There was a significant (P = 0.02) group * time interaction in low flow-mediated constriction (L-FMC) between MICT (0.63 +/- 2.00% vs. -2.79 +/- 3.20%; P = 0.03) and HIIT (-1.04 +/- 4.09% vs. 1.74 +/- 3.46%; P = 0.29). Vo2 max increased (P < 0.01) similarly after HIIT (2.19 +/- 0.65 l/min vs. 2.64 +/- 0.88 l/min) and MICT (2.24 +/- 0.48 l/min vs. 2.55 +/- 0.61 l/min). Biomarkers of cardiovascular risk and endothelial function were unchanged. HIIT and MICT produced different vascular adaptations in obese adults, with HIIT improving FMD and MICT increasing resting artery diameter and enhancing L-FMC. HIIT required 27.5% less total exercise time and ~25% less energy expenditure than MICT. PMID- 27255525 TI - Aerobic training prevents oxidative profile and improves nitric oxide and vascular reactivity in rats with cardiometabolic alteration. AB - Cardiovascular disease is the major cause of death worldwide; therefore it is important to understand the natural history of the pathophysiologic process and develop strategies to halt its progression. Thus this study investigated the protective effect of aerobic training on pathophysiological mechanisms involved in subclinical cardiometabolic alterations in a model with constant exposure to a prejudicial agent. Male Wistar rats were divided into a control group (C), which received drinking water, fructose group (F), which was fed 10% fructose in drinking water for 10 wk, and control training (CT) and fructose training groups (FT), in which moderate aerobic training was added in the last 8 wk of the study. Insulin, triacylglycerol, and isoprostane were higher and superoxide dismutase (SOD) was lower in the F group. There was no difference in thoracic aorta histology, but a decreased vascularization was seen in the F group, avoided by training in left ventricle. Regarding vascular function, the F group exhibited increased vasoconstrictory reactivity to phenylephrine. The F group presented impaired vasodilation to acetylcholine. Regarding endothelial nitric oxide synthase (eNOS), the F group presented a lower expression, and phosphorylated eNOS was higher in the trained groups than in their respective control groups. This same pattern was observed for nitric oxide bioavailability, antioxidant protein expression in aorta, left ventricle, and muscle (catalase, SOD, and glutathione peroxidase), serum SOD activity, and muscle mass. These results suggest that exercise training enhanced the antioxidant pathway and, as a consequence, the eNOS pathway, preventing an impairment in vascular vasodilatory capacity. PMID- 27255527 TI - Leishmania DNA Replication Timing: A Stochastic Event? AB - For eukaryotic genomes, DNA synthesis initiates at multiple discrete regions known as replication origins in a dynamic yet regulated manner to ensure genomic stability. Two recent studies using different approaches reveal few Leishmania origins and that origin firing may proceed in a mainly stochastic manner. PMID- 27255526 TI - Cattle and Nematodes Under Global Change: Transmission Models as an Ally. AB - Nematode infections are an important economic constraint to cattle farming. Future risk levels and transmission dynamics will be affected by changes in climate and farm management. The prospect of altered parasite epidemiology in combination with anthelmintic resistance requires the adaptation of current control approaches. Mathematical models that simulate disease dynamics under changing climate and farm management can help to guide the optimization of helminth control strategies. Recent efforts have increasingly employed such models to assess the impact of predicted climate scenarios on future infection pressure for gastrointestinal nematodes (GINs) in cattle, and to evaluate possible adaptive control measures. This review aims to consolidate progress in this field to facilitate further modeling and application. PMID- 27255528 TI - CONTRASTING CONCURRENT AND CHILDHOOD SOCIOECONOMIC PREDICTORS OF SELF-RATED HEALTH AMONG OLDER EUROPEAN MEN AND WOMEN. AB - This study aimed to assess the relative importance of childhood and adulthood socioeconomic position (SEP) on the self-rated health (SRH) of men and women aged 50 or higher in Europe, controlling for a substantial number of mediators and health conditions. Data from Wave 2 (current data) and Wave 3 (retrospective material) of the Survey of Health, Ageing and Retirement in Europe (SHARE) were combined (N=20,829) and logistic regression models applied; the analysis was carried out for males and females separately. The findings indicate that concurrent and past SEP, when considered separately, are both very significant predictors of SRH. When all factors were included in a comprehensive model most childhood and adult SEP variables retained their significance, implying that both types of socioeconomic circumstances have a strong and independent effect on SRH. However, the relative importance of several childhood indicators was reduced, signifying that their effect on SRH is mediated by adult SEP and, especially, educational attainment. Some childhood predictors, such as having experienced a period of hunger, remained very significant. Though these findings roughly hold for both sexes, the relative effects differentiate by sex. Current SEP is more important among women, with the exception of income and 'making ends meet in the household'. Childhood SEP indicators are more significant among men. PMID- 27255529 TI - Could we use a lower dose of rituximab to treat rheumatoid arthritis in clinical practice: pros and cons? AB - The CERERRA database provides evidence that low-dose rituximab performs as well as the conventional dose in the real world, thus highlighting the possible pharmacoeconomic impact. In clinical trials, it has been shown that rituximab 500 mg twice, performs as well as 1 g twice, 2 weeks apart, in terms of the American College of Rheumatology (ACR)20 and ACR50, but not the ACR70. The choice should always be made after considering that the IMAGE trial has demonstrated similar radiographic progression after the first 6 months, but with less control, with low-dose rituximab in the first 6 months. A possible alternative can be hypothesized. PMID- 27255530 TI - [Bilateral retinal detachment]. PMID- 27255531 TI - [Bilateral crystalline deposits in corneal stroma]. PMID- 27255533 TI - Racial disparities in individual breast cancer outcomes by hormone-receptor subtype, area-level socio-economic status and healthcare resources. AB - The aim of the study is to determine the influence of area-level socio-economic status and healthcare access in addition to tumor hormone-receptor subtype on individual breast cancer stage, treatment, and mortality among Non-Hispanic (NH) Black, NH-White, and Hispanic US adults. Analysis was based on 456,217 breast cancer patients in the SEER database from 2000 to 2010. Multilevel and multivariable-adjusted logistic and Cox proportional hazards regression analysis was conducted to account for clustering by SEER registry of diagnosis. NH-Black women had greater area-level access to healthcare resources compared with women of other races. For instance, the average numbers of oncology hospitals per million population in counties with NH-Black, NH-White, and Hispanic women were 8.1, 7.7, and 5.0 respectively; average numbers of medical doctors per million in counties with NH-Black, NH-White, and Hispanic women were 100.7, 854.0, and 866.3 respectively; and average number of Ob/Gyn in counties with NH-Black, NH-White, and Hispanic women was 155.6, 127.4, and 127.3, respectively (all p values <0.001). Regardless, NH-Black women (HR 1.39, 95 % CI 1.36-1.43) and Hispanic women (HR 1.05, 95 % CI 1.03-1.08) had significantly higher breast cancer mortality compared with NH-White women even after adjusting for hormone-receptor subtype, area-level socio-economic status, and area-level healthcare access. In addition, lower county-level socio-economic status and healthcare access measures were significantly and independently associated with stage at presentation, surgery, and radiation treatment as well as mortality after adjusting for age, race/ethnicity, and HR subtype. Although breast cancer HR subtype is a strong, important, and consistent predictor of breast cancer outcomes, we still observed significant and independent influences of area-level SES and HCA on breast cancer outcomes that deserve further study and may be critical to eliminating breast cancer outcome disparities. PMID- 27255534 TI - Therapeutic inhibition of breast cancer bone metastasis progression and lung colonization: breaking the vicious cycle by targeting alpha5beta1 integrin. AB - At diagnosis, 10 % of breast cancer patients already have locally advanced or metastatic disease; moreover, metastasis eventually develops in at least 40 % of early breast cancer patients. Osteolytic bone colonization occurs in 80-85 % of metastatic breast cancer patients and is thought to be an early step in metastatic progression. Thus, breast cancer displays a strong preference for metastasis to bone, and most metastatic breast cancer patients will experience its complications. Our prior research has shown that the alpha5beta1 integrin fibronectin receptor mediates both metastatic and angiogenic invasion. We invented a targeted peptide inhibitor of activated alpha5beta1, Ac-PHSCN-NH2 (PHSCN), as a validated lead compound to impede both metastatic invasion and neovascularization. Systemic PHSCN monotherapy prevented disease progression for up to 14 months in Phase I clinical trial. Here, we report that the next generation construct, Ac-PhScN-NH2 (PhScN), which contains D-isomers of histidine (h) and cysteine (c), is greater than 100,000-fold more potent than PHSCN at blocking basement membrane invasion. Moreover, PhScN is also up to 10,000-fold more potent than PHSCN at inhibiting lung extravasation and colonization in athymic mice for both MDA-MB-231 metastatic and SUM149PT inflammatory breast cancer cells. Furthermore, we show that systemic treatment with 50 mg/kg PhScN monotherapy reduces established intratibial MDA-MB-231 bone colony progression by 80 %. Thus, PhScN is a highly potent, well-tolerated inhibitor of both lung colonization and bone colony progression. PMID- 27255532 TI - The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium inaugural meeting report. AB - The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is a novel, interdisciplinary initiative comprised of experts across many fields, including genomics, data analysis, engineering, public health, and architecture. The ultimate goal of the MetaSUB Consortium is to improve city utilization and planning through the detection, measurement, and design of metagenomics within urban environments. Although continual measures occur for temperature, air pressure, weather, and human activity, including longitudinal, cross-kingdom ecosystem dynamics can alter and improve the design of cities. The MetaSUB Consortium is aiding these efforts by developing and testing metagenomic methods and standards, including optimized methods for sample collection, DNA/RNA isolation, taxa characterization, and data visualization. The data produced by the consortium can aid city planners, public health officials, and architectural designers. In addition, the study will continue to lead to the discovery of new species, global maps of antimicrobial resistance (AMR) markers, and novel biosynthetic gene clusters (BGCs). Finally, we note that engineered metagenomic ecosystems can help enable more responsive, safer, and quantified cities. PMID- 27255536 TI - Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD. AB - OBJECTIVE: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). METHOD: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to functional impairment were investigated. RESULTS: The MEWS functioned well as a brief measure of excessive MW in adult ADHD, showing good internal consistency (alpha > .9), and high sensitivity (.9) and specificity (.9) for the ADHD diagnosis, comparable with that of existing ADHD symptom rating scales. Elevated levels of MW were found in adults with ADHD, which contributed to impairment independently of core ADHD symptom dimensions. CONCLUSION: Findings suggest excessive MW is a common co-occurring feature of adult ADHD that has specific implications for the functional impairments experienced. The MEWS has potential utility as a screening tool in clinical practice to assist diagnostic assessment. PMID- 27255535 TI - Selective activity of deguelin identifies therapeutic targets for androgen receptor-positive breast cancer. AB - Triple-negative breast cancers (TNBC) are aggressive malignancies with no effective targeted therapies. Recent gene expression profiling of these heterogeneous cancers and the classification of cell line models now allows for the identification of compounds with selective activities against molecular subtypes of TNBC. The natural product deguelin was found to have selective activity against MDA-MB-453 and SUM-185PE cell lines, which both model the luminal androgen receptor (LAR) subtype of TNBC. Deguelin potently inhibited proliferation of these cells with GI50 values of 30 and 61 nM, in MDA-MB-453 and SUM-185PE cells, respectively. Deguelin had exceptionally high selectivity, 197 to 566-fold, for these cell lines compared to cell lines representing other TNBC subtypes. Deguelin's mechanisms of action were investigated to determine how it produced these potent and selective effects. Our results show that deguelin has dual activities, inhibiting PI3K/Akt/mTOR signaling, and decreasing androgen receptor levels and nuclear localization. Based on these data, we hypothesized that the combination of the mTOR inhibitor rapamycin and the antiandrogen enzalutamide would have efficacy in LAR models. Rapamycin and enzalutamide showed additive effects in MDA-MB-453 cells, and both drugs had potent antitumor efficacy in a LAR xenograft model. These results suggest that the combination of antiandrogens and mTOR inhibitors might be an effective strategy for the treatment of androgen receptor-expressing TNBC. PMID- 27255537 TI - Asymmetric epiphyseal closure of the femoral head as a potential cause of the primary cam lesion: a case report. AB - Cam-type femoroacetabular impingement is a pathologic condition caused by repetitive impact of the abnormal femur on a normal acetabular rim, resulting in damage to the articular cartilage. Excluding cases with known underlying diseases, the development of primary cam deformity is not well understood. Here, we describe a patient with cam-type femoroacetabular impingement exhibiting delayed epiphyseal closure at the site of the cam lesion. The authors believe that this may represent a cause of primary cam deformity, and hereby report the case with review of the literature. PMID- 27255538 TI - Hypercortisolism due to a Pituitary Adenoma Associated with Beckwith-Wiedemann Syndrome. AB - BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome with an increased risk of cancer. Most BWS patients show a molecular defect in the 11p15 region that contains imprinted genes. BWS has been associated with malignant neoplasms during infancy. Descriptions of benign tumors, especially in adult patients, are rarer. METHODS/RESULTS: We report the case of a BWS patient with pituitary adenoma caused by loss of methylation (LOM) at ICR2 (locus CDKN1C/KCNQ1OT1). The patient was referred to an endocrinology unit for suspicion of Cushing's disease due to a history of macroglossia and hemihyperplasia. Biological tests led to the diagnosis of ACTH-dependent hypercortisolism. MRI showed a microadenoma of the pituitary gland, confirming the diagnosis of Cushing's disease. DNA methylation analysis revealed LOM at ICR2 that was in a mosaic state in the patient's leukocytes, but was present in nearly all cells of the pituitary adenoma. The epigenetic defect was associated with a somatic USP8 mutation in the adenoma. CONCLUSION: Pituitary adenoma rarely occurs in patients with BWS. However, BWS should be considered in cases of pituitary adenoma with minor and/or major signs of BWS. The association between ICR2 LOM and USP8 mutation in the adenoma is questionable. (c) 2016 S. Karger AG, Basel. PMID- 27255539 TI - Reprint of: Microglial toll-like receptors and Alzheimer's disease. AB - Microglial activation represents an important pathological hallmark of Alzheimer's disease (AD), and emerging data highlight the involvement of microglial toll-like receptors (TLRs) in the course of AD. TLRs have been observed to exert both beneficial and detrimental effects on AD-related pathologies, and transgenic animal models have provided direct and credible evidence for an association between TLRs and AD. Moreover, analyses of genetic polymorphisms have suggested interactions between genetic polymorphisms in TLRs and AD risk, further supporting the hypothesis that TLRs are involved in AD. In this review, we summarize the key evidence in this field. Future studies should focus on exploring the mechanisms underlying the potential roles of TLRs in AD. PMID- 27255540 TI - The roles of RelA/(p)ppGpp in glucose-starvation induced adaptive response in the zoonotic Streptococcus suis. AB - The (p)ppGpp signal molecules play a central role in the stringent response (SR) to adapt to nutrient starvation in bacteria, yet the carbohydrate starvation induced adaptive response and the roles of SR in this response is not well characterized, especially in Gram-positives. Here, two (p)ppGpp synthetases RelA and RelQ are identified in Streptococcus suis, an important emerging zoonotic Gram-positive bacterium, while only RelA is functional under glucose starvation. To characterize the roles of RelA/(p)ppGpp in glucose starvation response in S. suis, the growth curves and transcriptional profiles were compared between the mutant strain DeltarelA [a (p)ppGpp(0) strain under glucose starvation] and its parental strain SC-19 [(p)ppGpp(+)]. The results showed great difference between SC-19 and DeltarelA on adaptive responses when suffering glucose starvation, and demonstrated that RelA/(p)ppGpp plays important roles in adaptation to glucose starvation. Besides the classic SR including inhibition of growth and related macromolecular synthesis, the extended adaptive response also includes inhibited glycolysis, and carbon catabolite repression (CCR)-mediated carbohydrate dependent metabolic switches. Collectively, the pheno- and genotypic characterization of the glucose starvation induced adaptive response in S. suis makes a great contribution to understanding better the mechanism of SR. PMID- 27255541 TI - Impact of sarcopenia on surgical site infection after restorative proctocolectomy for ulcerative colitis. AB - PURPOSE: The coexistence of sarcopenia is associated with postoperative complications, including infection after abdominal surgery. We evaluated the association between sarcopenia and surgical site infection (SSI) after surgery for ulcerative colitis. METHODS: The subjects of this retrospective study were 69 patients who underwent restorative proctocolectomy with perioperative abdominal computed tomography (CT). Sarcopenia was diagnosed by measuring the cross sectional area of the right and left psoas muscles as the total psoas muscle area on CT images. We assessed whether sarcopenia was associated with SSI and clinical factors, including nutritional and inflammatory markers. RESULTS: The lowest quartiles defined as sarcopenia in men and women were 567.4 and 355.8 mm2/m2, respectively. According to this classification, 12 men and 6 women had sarcopenia. Patients with sarcopenia had a lower body mass index (p = 0.0004) and a higher C-reactive protein concentration (p = 0.05) than those without sarcopenia. SSIs were identified in 12 patients (17.3 %) and included six pelvic abscesses and seven wound infections. According to multivariate analysis, sarcopenia was an independent risk factor for SSI (odds ratio = 4.91, 95 % confidence interval 1.09-23.5, p = 0.03). CONCLUSION: Sarcopenia is predictive of SSI after pouch surgery for ulcerative colitis. PMID- 27255543 TI - Epilepsy in pregnancy. PMID- 27255542 TI - Validity of linear measurements of the jaws using ultralow-dose MDCT and the iterative techniques of ASIR and MBIR. AB - PURPOSE: To assess the comparability of linear measurements of dental implant sites recorded from multidetector computed tomography (MDCT) images obtained using standard-dose filtered backprojection (FBP) technique with those from various ultralow doses combined with FBP, adaptive statistical iterative reconstruction (ASIR), and model-based iterative reconstruction (MBIR) techniques. The results of the study may contribute to MDCT dose optimization for dental implant site imaging. METHODS: MDCT scans of two cadavers were acquired using a standard reference protocol and four ultralow-dose test protocols (TP). The volume CT dose index of the different dose protocols ranged from a maximum of 30.48-36.71 mGy to a minimum of 0.44-0.53 mGy. All scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Linear measurements were recorded from standardized images of the jaws by two examiners. Intra- and inter-examiner reliability of the measurements were analyzed using Cronbach's alpha and inter-item correlation. Agreement between the measurements obtained with the reference-dose/FBP protocol and each of the test protocols was determined with Bland-Altman plots and linear regression. Statistical significance was set at a P-value of 0.05. RESULTS: No systematic variation was found between the linear measurements obtained with the reference protocol and the other imaging protocols. The only exceptions were TP3/ASIR-50 (bone kernel) and TP4/ASIR-100 (bone and standard kernels). The mean measurement differences between these three protocols and the reference protocol were within +/-0.1 mm, with the 95 % confidence interval limits being within the range of +/ 1.15 mm. CONCLUSIONS: A nearly 97.5 % reduction in dose did not significantly affect the height and width measurements of edentulous jaws regardless of the reconstruction algorithm used. PMID- 27255544 TI - Autism is underdiagnosed in prisoners. PMID- 27255545 TI - Unmasking Partial Seizure after Deep Brain Stimulation for Treatment-Resistant Depression: A Case Report. PMID- 27255546 TI - Influence of loading rate and modes on infiltration of treated wastewater in soil based constructed wetland. AB - Over the last 10 years soil-based constructed wetlands for discharge of treated wastewater (TWW) are commonly presented as a valuable option to provide tertiary treatment. The uncomplete knowledge in soil modifications and a lack of clear design practices laid the foundation of this work. The aim of this study was to determine optimal hydraulic loads and to observe the main critical parameters affecting treating performances and hydraulic loads acceptance. For this purpose, a soil rich in clay and backfill was chosen to perform column infiltration tests with TWW. Two loading rates and two loading modes were compared to study the influence of an intermittent feeding. Inlet and outlet waters were periodically analysed and columns were instrumented with balances, tensiometers, O2 and temperature probes. Soil physico-chemical characteristics were also taken into account to better understand the modification of the soil. One of the main expectations of tertiary treatment is to improve phosphate removal. A particular attention was thus given to phosphorus retention. The interest of an intermittent feeding in presence of a soil with high clay content was showed. This study highlighted that an intermittent feeding could make possible the use of a clay rich soil for water infiltration. PMID- 27255547 TI - Amino acid transporter B(0)AT1 (slc6a19) and ancillary protein: impact on function. AB - Amino acids play an important role in the metabolism of all organisms. Their epithelial re-absorption is due to specific transport proteins, such as B(0)AT1, a Na(+)-coupled neutral amino acid symporter belonging to the solute carrier 6 family. Here, a recently cloned fish orthologue, from the intestine of Salmo salar, was electrophysiologically characterized with the two-electrode voltage clamp technique, in Xenopus laevis oocytes heterologously expressing the transporter. Substrate specificity, apparent affinities and the ionic dependence of the transport mechanism were determined in the presence of specific collectrin. Results demonstrated that like the human, but differently from sea bass (Dicentrarchus labrax) orthologue, salmon B(0)AT1 needs to be associated with partner proteins to be correctly expressed at the oocyte plasma membrane. Cloning of sea bass collectrin and comparison of membrane expression and functionality of the B(0)AT1 orthologue transporters allowed a deeper investigation on the role of their interactions. The parameters acquired by electrophysiological and immunolocalization experiments in the mammalian and fish transporters contributed to highlight the dynamic of relations and impacts on transport function of the ancillary proteins. The comparative characterization of the physiological parameters of amino acid transporters with auxiliary proteins can help the comprehension of the regulatory mechanism of essential nutrient absorption. PMID- 27255548 TI - Detection of cell surface calreticulin as a potential cancer biomarker using near infrared emitting gold nanoclusters. AB - Calreticulin (CRT) is a cytoplasmic calcium-binding protein. The aim of this study was to investigate CRT presence in cancer with the use of fluorescent gold nanoclusters (AuNCs) and to explore AuNC synthesis using mercaptosuccinic acid (MSA) as a coating agent. MSA-coated AuNCs conferred well-dispersed, bio-stable, water-soluble nanoparticles with bioconjugation capacity and 800-850 nm fluorescence after broad-band excitation. Cell-viability assay revealed good AuNC tolerability. A native CRT amino-terminus corresponding peptide sequence was synthesised and used to generate rabbit site-specific antibodies. Target specificity was demonstrated with antibody blocking in colorectal and breast cancer cell models; human umbilical vein endothelial cells served as controls. We demonstrated a novel route of AuNC/MSA manufacture and CRT presence on colonic and breast cancerous cell surface. AuNCs served as fluorescent bio-probes specifically recognising surface-bound CRT. These results are promising in terms of AuNC application in cancer theranostics and CRT use as surface biomarker in human cancer. PMID- 27255549 TI - Diagnostic investigations of DKK-1 and PDCD5 expression levels as independent prognostic markers of human chondrosarcoma. AB - In this study, we investigated the expression levels of Dickkopf-1 (DKK-1) and programmed cell death 5 (PDCD5) by using quantitative real-time PCR and immunohistochemistry in patients with chondrosarcoma. The DKK-1 mRNA levels were significantly higher in chondrosarcoma when compared with the corresponding nontumor tissues (mean +/- SD: 4.23 +/- 1.54; 1.54 +/- 0.87; P = 0.001). PDCD5 mRNA levels were remarkably deceased in tumor tissues when compared with corresponding nontumor tissues (mean +/- SD: 1.94 +/- 0.73; 5.42 +/- 1.73; P = 0.001). The high and moderate DKK-1 expressions were observed for 60% of chondrosarcoma samples in comparison with 27.5% of corresponding nontumor tissues (P = 0.001). Moreover, low expression of PDCD5 was found in 67.5% of the tumor tissues when compared with the nontumor tissues (32.5%; P = 0.002). The results of this study showed that high DKK-1 expression levels were strongly related to MSTS stage (P = 0.011) and the advancement of histological grade (P < 0.001). Furthermore, the PDCD5 expression levels were correlated with histological grade (P < 0.001), MSTS stage (P = 0.016), and distant metastasis (P = 0.001). Kaplan Meier survival and log-rank survival showed that patients with high DKK-1 levels and low PDCD5 levels were correlated with shorter overall survival (log-rank test P < 0.001). PDCD5 levels, histological grade, and tumor stage were independent predictors of overall survival. In conclusion, DKK-1 and PDCD5 can be independent predictors of overall survival in patients suffering from chondrosarcoma. (c) 2016 IUBMB Life, 68(7):597-601, 2016. PMID- 27255550 TI - Zika Virus Infection: An Emerging Disease the Dermatologist Must Know About. PMID- 27255551 TI - [Osteogenic tumors of bone]. AB - BACKGROUND: Osteogenic tumors include malignant and benign tumors that produce tumor osteoid and/or bone tissue. Osteosarcoma is the most common malignant bone tumor, especially in children and young adults. OBJECTIVES: The entities with their characteristic morphological features are described to enable the reader to come to a diagnosis and differential diagnosis on the basis of patient age, history and predominant location of the tumor. METHODS: For this review we selectively used mainly large published patient cohorts. Our own and externally published data on widely accepted tumor criteria were also compared. RESULTS: Detection is the initial diagnostic step for an osseous lesion, and is determined by the sensitivity of the method applied. Plain X-ray films in two planes and CT are the basics in the radiological toolkit for osteogenic tumors. For evaluation of local tumor extension and biopsy planning MRI or scintigraphy should be combined. MRI as a stand-alone diagnostic tool is insufficient. For malignant bone tumors staging should be performed, applying a variable combination of thoracic CT, MRI, scintigraphy, and positron emission tomography (PET). Osteosarcoma, along with Ewing sarcoma and chondrosarcoma, are the most common malignant bone tumors; all sub-entities are significantly rarer. Among benign bone tumors, osteoid osteomas have the highest incidence, presenting with typical pain, location, and age predilection. CONCLUSIONS: Diagnostics and treatment of malignant bone tumors should preferably be performed in specialized centers because of significant therapeutic implications for patients. In uncertain cases, a second opinion should always be obtained. PMID- 27255552 TI - Paternal under-nutrition programs metabolic syndrome in offspring which can be reversed by antioxidant/vitamin food fortification in fathers. AB - There is an ever increasing body of evidence that demonstrates that paternal over nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health. PMID- 27255553 TI - Genistein regulates tumor microenvironment and exhibits anticancer effect in dimethyl hydrazine-induced experimental colon carcinogenesis. AB - Colon cancer is one of the leading causes of cancer mortality, worldwide. Cancer stem cells are attractive targets for therapeutic interventions since their abnormal growth may trigger tumor initiation, progression, and recurrence. Colon cancer in rats were induced with 1, 2-dimethyl hydrazine (DMH) and treated with genistein, an isoflavone rich in the soy food products, which also possesses various biological activities. Genistein treatment regulates enzymatic and non enzymatic anti-oxidants in the DMH-induced colonic tissue microenvironment. Alcian blue staining in colonic tissue reveals that mucin secretion was found to be depleted in DMH-induced group of animals. The alterations were normalized in the genistein-treated groups. Also, the mast cell population and collagen deposition were reduced as compared to induced group. Genistein treatment reduces the prognostic marker Argyrophilic nuclear organizer region (AgNOR) and proliferating cell nucleolar antigen (PCNA) in DMH-induced group of rats. DMH administration induces oxidative stress, whereas genistein activates nuclear factor-erythroid 2 related factor 2 (Nrf-2) and its downstream target hemoxygenase-1 (HO-1). Colonic stem cell marker protein CD133, CD44, and beta catenin expressions were found to be increased in DMH-induced group of animals as compared to control group of rats. Genistein treatment suppressed the expression of these stem cell markers suggesting rapid dysfunctional activation and proliferation of colonic stem cell-induced by DMH. The results of this study indicate that genistein administration in rats restored the colonic niche that was damaged by DMH and inhibits colon cancer progression. (c) 2016 BioFactors, 42(6):623-637, 2016. PMID- 27255554 TI - Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection. AB - BACKGROUND: Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the association between HK2 and Beta2AR expressions in HCC tissues, and to evaluate the synergistic effect of HK2 and Beta2AR in HCC prognosis. METHODS: Immunohistochemistry of HK2 and Beta2AR was performed on 155 paraffin embedded HCC samples retrieved from the archives of pathology department. Corresponding clinical data and prognostic data were collected through searching medical record systems, death registration systems and interviews with patient families. Spearman correlation test was performed to evaluate the association between HK2 and Beta2AR expression. Kaplan Meier survival curves and Cox regressions were employed to evaluate HK2 and Beta2AR expression in HCC prognosis, respectively and synergistically. RESULTS: 109 of 155 HCC patients reached the death point, the survival time of HCC patients was 46.23 +/- 31.01 months after curative surgical resections of HCC. Kaplan-Meier survival analysis showed that large tumor size (more than 5 cm) (hazard ratio (HR) = 8.42, 95 % confidence interval (CI) = 3.81-18.59, P < 0.0001), advanced TNM stage (III and IV stages) (HR = 2.09, 95%CI = 1.21-3.62, P < 0.001) and AFP more than 20 MUg/L (HR = 1.49, 95%CI = 1.02-2.18, P = 0.0302) were predictors for poor prognosis. HK2 and Beta2AR positive expression was detected in 66 (42.58) and 122 (78.71 %) HCC samples respectively. In univariate analysis, HK2(+) (HR = 2.70, 95%CI = 1.76-4.15, P < 0.0001) and Beta2AR(+) (HR = 4.61, 96%CI = 3.14-6.76, P < 0.0001) were associated with poor prognosis. In multivariate analysis, HK2(+) (P < 0.0001) and Beta2AR(+) (P < 0.0001) were also associated with poor prognosis. HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(-)/Beta2AR(-) in both univariate analysis (HR = 4.69, 95%CI = 2.91-7.57, P < 0.0001) and multivariate analysis (P < 0.0001). HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2( )/Beta2AR(+) in both univariate analysis (HR = 1.76, 95%CI = 1.17-2.64, P = 0.003) and multivariate analysis (P = 0.004). CONCLUSION: HK2 and Beta2AR play important roles in HCC progression. HK2 and Beta2AR expression in HCC is correlated positively. Beta2AR may increase HCC invasion and metastasis in collaboration with HK2. HK2 and Beta2AR can predict HCC prognosis both independently and synergistically. PMID- 27255555 TI - Strong association between glucocerebrosidase mutations and Parkinson's disease in Sweden. AB - Several genetic studies have demonstrated an association between mutations in glucocerebrosidase (GBA), originally implicated in Gaucher's disease, and an increased risk of Parkinson's disease (PD). We have investigated the possible involvement of genetic GBA variations in PD in the Swedish population. Three GBA variants, E326K, N370S, and L444P were screened in the largest Swedish Parkinson cohort reported to date; 1625 cases and 2025 control individuals. We found a significant association with high effect size of the rare variant L444P with PD (odds ratio 8.17; 95% confidence interval: 2.51-26.23; p-value = 0.0020) and a significant association of the common variant E326K (odds ratio 1.60; 95% confidence interval: 1.16-2.22; p-value = 0.026). The rare variant N370S showed a trend for association. Most L444P carriers (68%) were found to reside in northern Sweden, which is consistent with a higher prevalence of Gaucher's disease in this part of the country. Our findings support the role of GBA mutations as risk factors for PD and point to lysosomal dysfunction as a mechanism contributing to PD etiology. PMID- 27255557 TI - Flavobacterium verecundum sp. nov., isolated from a freshwater river. AB - Strain TTM-46T, isolated from a water sample taken from the Caohu River in Taiwan, was characterized using a polyphasic taxonomy approach. Cells of TTM-46T were Gram-staining-negative, strictly aerobic, motile by gliding, rod-shaped, surrounded by a thick capsule and formedyellowish-green colored colonies. Growth occurred at 20-30 degrees C (optimum, 30 degrees C), at pH 6-8 (optimum, pH 7) and with 0-0.3 % NaCl (optimum, 0 % w/v). Phylogenetic analyses based on 16 S rRNA gene sequences showed that TTM-46T represented a member of the genus Flavobacterium and was most closely related to Flavobacterium columnare IFO 15943T and Flavobacterium brevivitae TTM-43T with a sequence similarity of 96.9 % for both. TTM-46T contained iso-C15 : 0, summed feature 9 (iso-C17 : 1omega9c and/or 10-methyl C16 : 0), iso-C17 : 0 3-OH, iso-C15 : 1 G, iso-C15 : 0 3-OH and summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) as the predominant fatty acids. The major isoprenoid quinone was MK-6. The polar lipid profile consisted of phosphatidylethanolamine, four uncharacterized aminophospholipids and five uncharacterized phospholipids. The major polyamine was homospermidine. The genomic DNA G+C content of TTM-46T was 39 mol%. On the basis of the phylogenetic inference and phenotypic data, TTM-46T was recognized as a representative of a novel species within the genus Flavobacterium. The name Flavobacterium verecundum sp. nov. is proposed, with TTM-46T (=BCRC 80914T=LMG 29005T=KCTC 42745T) as the type strain. PMID- 27255556 TI - Quantum mechanical effects in plasmonic structures with subnanometre gaps. AB - Metallic structures with nanogap features have proven highly effective as building blocks for plasmonic systems, as they can provide a wide tuning range of operating frequencies and large near-field enhancements. Recent work has shown that quantum mechanical effects such as electron tunnelling and nonlocal screening become important as the gap distances approach the subnanometre length scale. Such quantum effects challenge the classical picture of nanogap plasmons and have stimulated a number of theoretical and experimental studies. This review outlines the findings of many groups into quantum mechanical effects in nanogap plasmons, and discusses outstanding challenges and future directions. PMID- 27255558 TI - Explaining outcomes in major system change: a qualitative study of implementing centralised acute stroke services in two large metropolitan regions in England. AB - BACKGROUND: Implementing major system change in healthcare is not well understood. This gap may be addressed by analysing change in terms of interrelated components identified in the implementation literature, including decision to change, intervention selection, implementation approaches, implementation outcomes, and intervention outcomes. METHODS: We conducted a qualitative study of two cases of major system change: the centralisation of acute stroke services in Manchester and London, which were associated with significantly different implementation outcomes (fidelity to referral pathway) and intervention outcomes (provision of evidence-based care, patient mortality). We interviewed stakeholders at national, pan-regional, and service-levels (n = 125) and analysed 653 documents. Using a framework developed for this study from the implementation science literature, we examined factors influencing implementation approaches; how these approaches interacted with the models selected to influence implementation outcomes; and their relationship to intervention outcomes. RESULTS: London and Manchester's differing implementation outcomes were influenced by the different service models selected and implementation approaches used. Fidelity to the referral pathway was higher in London, where a 'simpler', more inclusive model was used, implemented with a 'big bang' launch and 'hands-on' facilitation by stroke clinical networks. In contrast, a phased approach of a more complex pathway was used in Manchester, and the network acted more as a platform to share learning. Service development occurred more uniformly in London, where service specifications were linked to financial incentives, and achieving standards was a condition of service launch, in contrast to Manchester. 'Hands-on' network facilitation, in the form of dedicated project management support, contributed to achievement of these standards in London; such facilitation processes were less evident in Manchester. CONCLUSIONS: Using acute stroke service centralisation in London and Manchester as an example, interaction between model selected and implementation approaches significantly influenced fidelity to the model. The contrasting implementation outcomes may have affected differences in provision of evidence-based care and patient mortality. The framework used in this analysis may support planning and evaluating major system changes, but would benefit from application in different healthcare contexts. PMID- 27255559 TI - Pharmacoepidemiological safety studies in children: a systematic review. AB - PURPOSE: In order to identify challenges in pediatric pharmacoepidemiological safety studies, we assessed the characteristics of such (published) studies. METHODS: Relevant articles from inception to 2013 were retrieved from Embase and Medline. We sequentially screened titles, abstracts and full texts with independent validation. We systematically collected data regarding general information, study methods and results. RESULTS: Out of 4825 unique articles, 268 full texts (5.6%) were retained; 147 (54.9%) pertained to drugs rather than vaccines. Considering the 268 studies, 202 (75.4%) concerned children and adolescents (2 to 11 years) and 14 (5.3%) included preterm newborns. Most studies originated from North America (154 [57.5%]) or Europe (92 [34.3%]). Only 47 studies (17.5%) were privately funded. The majority (174 [64.9%]) were cohort studies. Out of 268 studies, 196 (73.1%) collected data retrospectively; paper medical charts were the most common data source for the exposures (85 [31.7%]) and outcomes (122 [45.5%]). Only 3 (2.0%) drug-only studies investigated rarely used drugs. Considering all 268 studies, only 27 (10.1%) reported sample size or power calculation. Most (75 [51.0%]) drug-only studies corrected confounding by multivariate modeling unlike stratification in 66 (55.9%) vaccine-only studies. Considering 75 child-only studies without any statistically significant result, 41 (54.7%) did not discuss lack of power. CONCLUSIONS: Although the field of pediatric pharmacoepidemiology is steadily developing evaluation seldom includes neonates, is mainly focused on few drug classes and safety outcomes and concerns mainly drug use in developed countries. Small study size is a specific challenge in pediatrics. Reporting should be improved. (c) 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. PMID- 27255560 TI - Dexamethasone as adjuvant for femoral nerve block following knee arthroplasty: a randomized, controlled study. AB - BACKGROUND: We examined the effect of the addition of dexamethasone to bupivacaine for femoral nerve blocks on the block duration and the quality of post-operative analgesia following total knee replacement surgery. METHODS: In total, 200 ASA I-III patients were randomly allocated to either the control group who received bupivacaine 0.5% or the dexamethasone group who received bupivacaine 0.5% plus 8 mg dexamethasone for the femoral nerve block, followed by a continuous perineural bupivacaine infusion started at the time of block resolution. Patients were assessed for the duration of analgesia by the return of pinprick sensation and the 24-h morphine consumption as the primary outcomes of the study. A numerical rating scale from 0 to 10 was used to assess post operative pain at zero, 1/2, 2, 6, 24, 48, and 72 h. RESULTS: There was no difference between groups in either sensory or motor block onset; however, the duration of the block was significantly prolonged in the dexamethasone group, 25.7 +/- 3 h, vs. 18.8 +/- 4 h in the control group P < 0.0001. The total morphine consumption was not different between groups, but the dexamethasone group consumed less morphine in the first 6 h post-operatively. The addition of dexamethasone improved pain control on the first post-operative day, but no difference in the pain score was detected on days 2 or 3. CONCLUSION: The addition of dexamethasone to bupivacaine for femoral nerve block prolonged the duration of analgesia, improved early post-operative pain following total knee arthroplasty. PMID- 27255561 TI - Applications of hierarchically structured porous materials from energy storage and conversion, catalysis, photocatalysis, adsorption, separation, and sensing to biomedicine. AB - Over the last decade, significant effort has been devoted to the applications of hierarchically structured porous materials owing to their outstanding properties such as high surface area, excellent accessibility to active sites, and enhanced mass transport and diffusion. The hierarchy of porosity, structural, morphological and component levels in these materials is key for their high performance in all kinds of applications. The introduction of hierarchical porosity into materials has led to a significant improvement in the performance of materials. Herein, recent progress in the applications of hierarchically structured porous materials from energy conversion and storage, catalysis, photocatalysis, adsorption, separation, and sensing to biomedicine is reviewed. Their potential future applications are also highlighted. We particularly dwell on the relationship between hierarchically porous structures and properties, with examples of each type of hierarchically structured porous material according to its chemical composition and physical characteristics. The present review aims to open up a new avenue to guide the readers to quickly obtain in-depth knowledge of applications of hierarchically porous materials and to have a good idea about selecting and designing suitable hierarchically porous materials for a specific application. In addition to focusing on the applications of hierarchically porous materials, this comprehensive review could stimulate researchers to synthesize new advanced hierarchically porous solids. PMID- 27255562 TI - Interaction Induced High Catalytic Activities of CoO Nanoparticles Grown on Nitrogen-Doped Hollow Graphene Microspheres for Oxygen Reduction and Evolution Reactions. AB - Nitrogen doped graphene hollow microspheres (NGHSs) have been used as the supports for the growth of the CoO nanoparticles. The nitrogen doped structure favors the nucleation and growth of the CoO nanoparticles and the CoO nanoparticles are mostly anchored on the quaternary nitrogen doped sites of the NGHSs with good monodispersity since the higher electron density of the quaternary nitrogen favors the nucleation and growth of the CoO nanoparticles through its coordination and electrostatic interactions with the Co(2+) ions. The resulting NGHSs supported CoO nanoparticles (CoO/NGHSs) are highly active for the oxygen reduction reaction (ORR) with activity and stability higher than the Pt/C and for the oxygen evolution reaction (OER) with activity and stability comparable to the most efficient catalysts reported to date. This indicates that the CoO/NGHSs could be used as efficient bi-functional catalysts for ORR and OER. Systematic analysis shows that the superior catalytic activities of the CoO/NGHSs for ORR and OER mainly originate from the nitrogen doped structure of the NGHSs, the small size of the CoO nanoparticles, the higher specific and electroactive surface area of the CoO/NGHSs, the good electric conductivity of the CoO/NGHSs, the strong interaction between the CoO nanoparticles and the NGHSs, etc. PMID- 27255563 TI - Physalis alkekengi and Alhagi maurorum ameliorate the side effect of cisplatin induced nephrotoxicity. AB - Cisplatin is frequently being used for the treatment of different tumors, although the application of this agent is associated with nephrotoxicity. Here, we explored the antioxidant and anti-inflammatory activities of Physalis alkekengi and Alhagi maurorum; 400 mg kg(-1) per day P. alkekengi and 100 mg kg( 1) per day A. maurorum were administered in rats, orally for 10 days after a single dose of 7 mg kg(-1) intraperitoneal cisplatin. The concentrations of creatinine, urea-nitrogen, and relative and absolute excretion of sodium/potassium were evaluated before/after therapy. Levels of malondialdehyde (MDA) and ferric-reducing antioxidant power (FRAP) were measured to assess the oxidative stress induced by cisplatin. Moreover, tissues sections were used for histological analyses and evaluation of the degree of tissue damage. Cisplatin increased serum levels of creatinine and urea-nitrogen, relative/absolute excretion of sodium/potassium, and MDA, whereas decreased FRAP level. Interestingly, P. alkekengi or A. maurorum were able to reduce the level of the renal function markers as well as the levels of sodium/potassium. This effect was more pronounced by P. alkekengi. Moreover, cisplatin induced pathological damage in kidney, whereas treatment with these agents improved this condition. Our findings demonstrate the potential therapeutic impact of P. alkekengi and A. maurorum for improving cisplatin-induced nephrotoxicity, supporting further investigations on the novel potential clinical application of these agents for patients being treated with cisplatin to ameliorate cisplatin-induced nephrotoxicity. PMID- 27255564 TI - Total pregnancy loss after chorionic villus sampling and amniocentesis: a cohort study. AB - OBJECTIVES: To identify maternal-, operator- and procedure-related variables that affect procedure-related pregnancy loss after transcervical (TC) and transabdominal (TA) chorionic villus sampling (CVS) and amniocentesis and to estimate the rates of spontaneous and procedure-related loss in comparable subgroups of women. METHODS: This was a retrospective cohort study conducted at the University Medical Center Groningen and the Academic Medical Center, The Netherlands. Databases of both centers were searched to identify singleton pregnancies that had undergone a combined test and/or anomaly scan at around 20 weeks' gestation, or an invasive procedure (CVS and/or amniocentesis) between January 2001 and December 2011. Maternal characteristics, obstetric history, technical aspects of the invasive procedure, ultrasound examinations and fetal and neonatal outcomes were available for 29 201 cases. Women were categorized, according to the type of examination they had received, into the following five groups: first-trimester combined test (and 20-week anomaly scan); 20-week anomaly scan only; CVS; amniocentesis; amniocentesis after unsuccessful CVS. Rates of fetal loss were compared between groups. RESULTS: Variables significantly associated with a higher rate of fetal loss were, for CVS, repeat attempts during the procedure, use of TC cannula instead of biopsy forceps, gestational age at procedure >= 13 weeks and a pregnancy after assisted reproductive techniques, and, for amniocentesis, if indication was fetal anomaly or family history of anomalies and repeat attempts during the procedure. In women aged >= 36 years who did not undergo an invasive procedure, spontaneous fetal loss rate (FLR) after first-trimester combined test was 1.40%, whereas after CVS, FLR was 2.76% and 2.43% for a TC and TA approach, respectively. The additional risk of fetal loss with TC-CVS was therefore 1.36% (1 : 74), which varied according to the instrument used (0.27% for forceps and 3.12% for cannula), and with TA-CVS was 1.03% (1 : 97). In women aged >= 36 years who underwent a 20-week anomaly scan only, spontaneous FLR was 0.63%. In women who underwent amniocentesis solely because of advanced maternal age, FLR was 1.11%. The additional risk of fetal loss with amniocentesis was 0.48% (1 : 208). CONCLUSION: The total rate of procedure-related fetal loss after TA- and TC-CVS and amniocentesis appears lower than the risks on which women are currently counseled. There was a trend for a decrease in risk when the level of experience of the operator increased. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27255565 TI - Erratum to: 'A cost and performance comparison of Public Private Partnership and public hospitals in Spain'. PMID- 27255567 TI - A multi-layer microchip for high-throughput single-cell gene expression profiling. AB - Microfluidics or Bio-MEMS technology offers significant advantages for performing high-throughput screens and sensitive assays. The ability to correlate single cell genetic information with cellular phenotypes is of great importance to biology and medicine because it holds the potential to gain insight into disease pathways that is unavailable from ensemble measurements. Previously, we reported two kinds of prototypes for integrated on-chip gene expression profiling at the single-cell level, and the throughput was designed to be 6. In this work, we present a five-layer microfluidic system for parallelized, rapid, quantitative analysis of RNA templates with low abundance at the single-cell level. The microchip contains two multiplexors and one partitioning valve group, and it leverages a matrix (6 * 8) of quantitative reverse transcription polymerase chain reaction (RT-qPCR) units formed by a set of parallel microchannels concurrently controlled by elastomeric pneumatic valves, thereby enabling parallelized handling and processing of biomolecules in a simplified operation procedure. A comprehensive metallic nanofilm with passivation layer is used to run polymerase chain reaction (PCR) temperature cycles. To demonstrate the utility of the approach, artificial synthesized RNA templates (XenoRNA) and mRNA templates from single cells are employed to perform the 48-readout RT-qPCRs. The PCR products are imaged on a fluorescence microscope using a hydrolysis probe/primer set (TaqMan). Fluorescent intensities of passive reference dye and a fluorescein amidite reporter dye are acquired and measured at the end of PCR cycles. PMID- 27255566 TI - Evaluation of Aloe vera and synbiotic as antibiotic growth promoter substitutions on performance, gut morphology, immune responses and blood constitutes of broiler chickens. AB - This study was performed to investigate the effect of dietary supplementation with Aloe vera (AV) powder and synbiotic as growth promoter agents on performance, gut morphology, immune responses, hematology and serum biochemistry in broilers. A total of 240-day-old male broiler chicks (Ross 308) were randomly assigned to six treatments with four replicates. Birds were offered either a corn soybean meal basal diet (control) or the basal diet supplemented with 200 mg/kg virginiamycin (VM), 1 g/kg synbiotic (Syn), 2.5 g/kg AV (AV1), 5.0 g/kg AV (AV2) or 7.5 g/kg AV (AV3). Chickens fed any of the diets, except diet AV1, exhibited better feed conversion ratios at the 14-28 day period and higher average daily gain and duodenal villus height/crypt depth ratio at 42 days than those fed the control diet. Synbiotic supplementation caused a marked increase in the serum antibody titer against infectious bursal disease and infectious bronchitis vaccines. Feeding diet AV3 significantly increased red blood cell count and hemoglobin concentration, and decreased serum triglyceride level compared to the control group. The results suggested that dietary inclusion of 5 and 7.5 g/kg AV, similar with synbiotic supplementation, can be applied as effective alternatives to in-feed antibiotics for broiler diets. PMID- 27255568 TI - Differential hypoxic response of human choroidal and retinal endothelial cells proposes tissue heterogeneity of ocular angiogenesis. AB - PURPOSE: To elaborate molecular differences between choroidal and retinal angiogenesis by generating and comparatively analysing human primary choroidal and retinal endothelial cell (CEC and REC) lines. METHODS: Human CEC and REC were isolated by positive selection and were cultured. Characterization was performed by immunostaining for endothelial cell (EC)-specific markers. Total RNA and protein were extracted from normoxic or hypoxic CEC and REC cultures. Quantitative polymerase chain reaction (PCR) arrays were used to comparatively analyse 133 genes between CEC and REC, and the expression differences were calculated by DeltaDeltaCt method. A total of 57 angiogenesis-related protein expression differences were investigated by Western blot and proteome profiler and were calculated by densitometry. RESULTS: Primary human CEC and REC lines stained positively for all EC markers and demonstrated high purity with similar staining and morphology. Under normoxia, CEC showed significantly lower expression levels for cell proliferation and vessel maturation genes and higher expression levels for inflammation-related genes when compared to REC. In response to hypoxia, CEC and REC displayed differential regulation for a multitude of angiogenesis-related genes and proteins. Furthermore, within the vascular endothelial growth factor (VEGF) family, CEC showed preferential upregulation for vascular endothelial growth factor A (VEGFA) while REC upregulated placenta growth factor (PlGF) levels. CONCLUSION: Differential normoxic and hypoxic regulation of angiogenesis-related factors by CEC and REC outlines tissue heterogeneity of ocular angiogenesis and suggests that tissue specificity should be considered as a novel treatment modality for successfully overcoming choroidal and retinal angiogenic conditions in the clinic. PMID- 27255569 TI - Delayed intracytoplasmic sperm injection (ICSI) with trophectoderm biopsy and preimplantation genetic screening (PGS) show increased aneuploidy rates but can lead to live births with single thawed euploid embryo transfer (STEET). AB - PURPOSE: The aim of this study was to report the results of IVF with trophectoderm biopsy and preimplantation genetic screening (PGS) following delayed intracytoplasmic sperm injection (ICSI). METHODS: Patients undergoing IVF with PGS and delayed ICSI were included in the study. Indications for delayed ICSI included absent or poor fertilization via standard insemination or more than 50 % immature oocytes, noted post-cumulus stripping for standard ICSI procedure. Delayed ICSI was performed the day after retrieval due to absent or poor fertilization. The immature oocytes were kept in extended culture, and if demonstrated maturity, ICSI was performed. Primary outcome included fertilization rate and blastocyst stage formation, defined by the number of blastocysts for biopsy. Secondary outcome included aneuploidy rate and pregnancy outcomes following single thawed euploid embryo transfers (STEET). RESULTS: Sixteen patients with delayed ICSI were included in the study. Twelve were due to poor fertilization and four secondary to immature oocytes. A total of 219 oocytes were retrieved; ten were frozen upon patient request, 168 had standard insemination, and 13 had routine ICSI on the day of retrieval. A total of 129 oocytes underwent delayed ICSI. Sixty-three (49 %) fertilized, 19 (14.7 %) reached blastocysts for biopsy; fivw of which were chromosomally normal (26.3 %). Three patients underwent STEET of a delayed ICSI embryo; all three resulted in live births, including one embryo biopsied on day 8 of development. CONCLUSION: Fertilization failure or an excessive proportion of immature oocytes in an IVF cycle, necessitating delayed ICSI, showed equivalent fertilization and blast formation rates. With the implementation of trophectoderm biopsy and PGS, these embryos can lead to healthy live born babies. PMID- 27255570 TI - Can Coenzyme Q10 supplementation protect the ovarian reserve against oxidative damage? AB - PURPOSE: We investigated antioxidant effects of CoQ10 supplementation on the prevention of OS-induced ovarian damage and to evaluate the protective effect of such supplementation against OS-related DNA damage. METHODS: Twenty-four adult female Sprague-Dawley rats were randomly divided into three groups (8 rats per group): group 1 (control): saline, ip, and orally; group 2 (cisplatin group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days; and group 3 (cisplatin + CoQ10 group): cisplatin, 4.5 mg/kg ip, two times with an interval of 7 days, and 24 h before cisplatin, 150 mg/kg/day orally in 1 mL of saline daily for 14 days. Serum concentrations of anti-Mullerian hormone (AMH), number of AMH positive follicles, the assessment of the intensity of 8'OHdG immunoreactivity, the primordial, antral and atretic follicle counts in the ovary were assessed. RESULT(S): The mean serum AMH concentrations were 1.3 +/- 0.19, 0.16 +/- 0.03, and 0.27 +/- 0.20 ng/mL in groups 1, 2, and 3, respectively (p < 0.01). Serum AMH levels were significantly higher in group 1 compared to groups 2 and 3 (p < 0.01 and p = 0.01, respectively). There was a statistically significant difference in AMH-positive follicle count between the groups (p < 0.01). Group 1 showed higher numbers of AMH-positive granulosa cells compared to group 2 (p = 0.01). A significant difference was found in the primordial, the atretic, and antral follicle counts between the three groups (p < 0.01, p < 0.01, and p < 0.01, respectively). The atretic follicle count was significantly lower in the cisplatin plus CoQ10 group compared to the cisplatin group (p < 0.01). The antral follicle counts were significantly higher in the cisplatin plus CoQ10 group compared with the cisplatin group (p < 0.01). There was a statistically significant difference in the intensity of staining of the follicles that were positive for anti-8'OHdG between the groups (p = 0.02). Group 1 showed a significant lower intensity of staining of the follicles positive for anti-8'OHdG compared with group 2 (p = 0.03). CONCLUSION(S): CoQ10 supplementation may protect ovarian reserve by counteracting both mitochondrial ovarian ageing and physiological programmed ovarian ageing although the certain effect of OS in female infertility is not clearly known. PMID- 27255571 TI - Combined inguinal hernia in the elderly. Portraying the progression of hernia disease. AB - INTRODUCTION: Identification of a combined hernia is a common occurrence in the course of inguinal hernia repair. This type of protrusion disease seems to affect the elderly, in particular. Very few investigations have been carried out to ascertain the structural changes that occur in the groin affected by this clinical condition. METHOD: Analysis of intraoperative findings of combined inguinal hernias evidenced in the elderly, from the most recent 100 groin hernia repair procedures carried out by a single operator, represents the basis of the article. Protrusions that presumably represent the forerunner of this type of hernia were also analyzed: double ipsilateral inguinal hernias composed of a direct and an indirect protrusion. The gross anatomical, as well as histological, modifications occurring during the development of combined protrusions were also evaluated. RESULTS: Combined hernia was the most frequent protrusion in patients over 65 years, accounting for 36% of the total in this patient group. In the same patient cohort, double inguinal hernia further involves 22% of elderly subjects. Macroscopically, progressive disruption of the inguinal back wall and degenerative reabsorption of the inferior epigastric vessels were evidenced. Histologically, inflammatory infiltrate, significant nerve and vascular injuries, along with severe muscle degeneration were recognized. CONCLUSIONS: The results seem to confirm that inguinal hernia is an unremitting progressive disease caused by chronic compressive structural damage. Combined hernias represent a frequent clinical condition in the elderly consequent to long-term degenerative damage. Therapy of combined protrusions must consider the impact of visceral vector forces. PMID- 27255572 TI - Zygomatic fractures: Technical modifications for better aesthetic and functional results in older patients. AB - INTRODUCTION: The zygomaticomaxillary complex, with its intrinsically prominent convexity, is highly vulnerable to injury. In this study, we evaluated a novel combined approach to the reduction and stabilization of frontozygomatic dislocated fractures without aesthetic damage. MATERIALS AND METHODS: Ten patients (mean age, 52 years) were referred for complex frontozygomatic dislocated fractures. Five patients underwent a transconjunctival approach without canthotomy in association with a transoral maxillary approach and lateral rim skin incision, also without canthotomy. The other five patients underwent a traditional subciliary incision at the lower eyelid and a vertical lateral incision at the lateral orbital margin. Orbital floor reconstruction was achieved using two to three fixation points and autologous platelet-rich fibrin (PRF). During the 6-month follow-up, the patients were routinely evaluated using computed tomography. RESULTS: Treatment was successful in all cases; there were no problems at surgery or postoperatively. During follow-up, all patients had satisfactory facial symmetry, no noticeable scar, ectropion, or lower-eyelid drop, and no functional impairment. DISCUSSION: Aesthetic considerations are an important aspect of treatment planning in patients with orbitozygomatic fractures, because of the importance of the eye and lid areas to facial aesthetics. In our patients, good aesthetic results were achieved using a novel combined approach. In patients with a large orbital floor dislocation, the reconstructive titanium mesh can be covered by autologous PRF membranes to improve vascularization of the surgical site. By preventing aesthetic damage and functional impairment, our conservative approach is of particular utility in older individuals due to age-related tissue laxity. PMID- 27255573 TI - Submental flap as an alternative to microsurgical flap in intraoral post oncological reconstruction in the elderly. AB - Oral and oropharyngeal squamous cell carcinoma (Scc) occur most commonly in middle-aged and elderly individuals. Free flaps are commonly used for reconstruction of extensive tumor resection defects in the oral cavity. Age alone is not an independent variable for increased risk in microvascular reconstruction; however operative time and ASA risk score correlated with medical complications but not with surgical complications. The submental island flap has proven to be a reliable alternative in reconstruction of composite oral cavity defects for its thinness, pliability and versatility in design, shared by the radial forearm free flap, and its advantageous donor site. The submental flap can be easily raised and involves shorter operative time and hospital stay compared to the free-flap procedure. It can be an excellent choice in patients with a high ASA risk score, moreover in elderly patients, where the potential complications linked to microsurgical procedures are avoided. PMID- 27255574 TI - Development of Multifunctional Fluorescent-Magnetic Nanoprobes for Selective Capturing and Multicolor Imaging of Heterogeneous Circulating Tumor Cells. AB - Circulating tumor cells (CTC) are highly heterogeneous in nature due to epithelial-mesenchymal transition (EMT), which is the major obstacle for CTC analysis via "liquid biopsy". This article reports the development of a new class of multifunctional fluorescent-magnetic multicolor nanoprobes for targeted capturing and accurate identification of heterogeneous CTC. A facile design approach for the synthesis and characterization of bioconjugated multifunctonal nanoprobes that exhibit excellent magnetic properties and emit very bright and photostable multicolor fluorescence at red, green, and blue under 380 nm excitation is reported. Experimental data presented show that the multifunctional multicolor nanoprobes can be used for targeted capture and multicolor fluorescence mapping of heterogeneous CTC and can distinguish targeted CTC from nontargeted cells. PMID- 27255575 TI - Discontinuation of peri-operative gentamicin use for indwelling urinary catheter manipulation in orthopaedic surgery. AB - BACKGROUND: Gentamicin has historically been used prior to insertion and removal of indwelling urinary catheters (IDCs) around elective joint replacement surgery to prevent infection; however, this indication is not recognized in the Australian Therapeutic Guidelines: Antibiotic and the paradigm for safe use of gentamicin has shifted. METHODS: The antimicrobial stewardship team of a 500 bed tertiary regional hospital performed a retrospective clinical study of gentamicin IDC prophylaxis around total hip and knee arthroplasties. Results were presented to the orthopaedic surgeons. A literature review identified no guidelines to support gentamicin prophylaxis and only a very low risk of bacteraemia associated with IDC insertion/removal in patients with established bacteriuria. Consensus was reached with the surgeons to discontinue this practice. Subsequent prospective data collection was commenced to determine effectiveness, with weekly feedback to the Department Head of Orthopaedics. RESULTS: Data from 137 operations pre-intervention (6 months) were compared with 205 operations post intervention (12 months). The median patient age was 72 years in both groups. Following the intervention, reductions in gentamicin use were demonstrated for IDC insertion (59/137 (42%) to 4/205 (2%), P < 0.01) and removal (39/137 (28%) to 6/205 (3%), P < 0.01). No gentamicin use was observed during the final 40 weeks of the post-intervention period. There were no significant differences between the groups for pre-operative bacteriuria, surgical site infections or acute kidney injury. CONCLUSION: A collaborative approach using quality improvement methodology can lead to an evidence-based reappraisal of established practice. Regular rolling audits and timely feedback were useful in sustaining change. PMID- 27255576 TI - Whole-exome sequencing implicates DGKH as a risk gene for panic disorder in the Faroese population. AB - The demographic history of the isolated population of the Faroe Islands may have induced enrichment of variants rarely seen in outbred European populations, including enrichment of risk variants for panic disorder (PD). PD is a common mental disorder, characterized by recurring and unprovoked panic attacks, and genetic factors have been estimated to explain around 40% of the risk. In this study the potential enrichment of PD risk variants was explored based on whole exome sequencing of 54 patients with PD and 211 control individuals from the Faroese population. No genome-wide significant associations were found, however several single variants and genes showed strong association with PD, where DGKH was found to be the strongest PD associated gene. Interestingly DGKH has previously demonstrated genome-wide significant association with bipolar disorder as well as evidence of association to other mental disorders. Additionally, we found an enrichment of PD risk variants in the Faroese population; variants with otherwise low frequency in more outbreed European populations. (c) 2016 Wiley Periodicals, Inc. PMID- 27255577 TI - Environmentally friendly power generator based on moving liquid dielectric and double layer effect. AB - An electrostatic power generator converts mechanical energy to electrical energy by utilising the principle of variable capacitance. This change in capacitance is usually achieved by varying the gap or overlap between two parallel metallic plates. This paper proposes a novel electrostatic micro power generator where the change in capacitance is achieved by the movement of an aqueous solution of NaCl. A significant change in capacitance is achieved due to the higher than air dielectric constant of water and the Helmholtz double layer capacitor formed by ion separation at the electrode interfaces. The proposed device has significant advantages over traditional electrostatic devices which include low bias voltage and low mechanical frequency of operation. This is critical if the proposed device is to have utility in harvesting power from the environment. A figure of merit exceeding 10000(10(8)MUW)/(mm(2)HzV(2)) which is two orders of magnitude greater than previous devices, is demonstrated for a prototype operating at a bias voltage of 1.2 V and a droplet frequency of 6 Hz. Concepts are presented for large scale power harvesting. PMID- 27255578 TI - Direct antiviral agents and risk for HCC early recurrence: Much ado about nothing. PMID- 27255579 TI - Reply to: "High volume plasma exchange in patients with acute liver failure". PMID- 27255580 TI - High volume plasma exchange in patients with acute liver failure. PMID- 27255581 TI - Reply to "Direct antiviral agents and risk for hepatocellular carcinoma (HCC) early recurrence: Much ado about nothing". PMID- 27255582 TI - Hepatocellular carcinoma recurrence after treatment with direct-acting antivirals: First, do no harm by withdrawing treatment. PMID- 27255583 TI - Effect of exercise on the development of new fatty liver and the resolution of existing fatty liver. AB - BACKGROUND & AIMS: Guidelines about recommendations for amounts of exercise/physical activity are variable in non-alcoholic fatty liver disease. Our aim was to determine the amount of exercise that was associated with two outcomes: a) development of incident liver fat and b) resolution of baseline liver fat, at five-year follow-up. METHODS: In an occupational health screening program, weekly frequency of exercise was assessed using the validated Korean version of the International Physical Activity Questionnaire Short Form (IPAQ SF). Liver fat was identified by ultrasonography (3.5MHz probe) at baseline and at five-year follow-up. Fully adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs and 95% confidence intervals [CI]) for incident fatty liver and resolution of fatty liver at follow-up. RESULTS: 233,676 men and women were studied between 2002 and 2014. 126,811 individuals were identified without fatty liver, and of these subjects, 29,014 subjects developed incident fatty liver during follow-up. At baseline, there were 42,536 individuals with liver fat and of these individuals, fatty liver resolved in 14,514, during follow up. After full adjustment, compared to no exercise, exercise was associated with benefit for both outcomes; for exercise ?5times per week for incident fatty liver: HR 0.86 (95% CI 0.80,0.92), p<0.001, and for resolution of fatty liver HR 1.40 (95% CI 1.25,1.55), p<0.001. CONCLUSIONS: Moderate to vigorous exercise is beneficial in decreasing risk of development of new fatty liver or improving resolution of existing fatty liver during 5years of follow-up. LAY SUMMARY: The amount of exercise/physical activity to benefit fatty liver disease in non alcoholic fatty liver disease is not known. In a large study of free-living people, our aim was to determine the amount of exercise that was linked with a decrease in new fatty liver and also improvement of existing fatty liver over 5years of follow-up. Compared to no exercise, exercise ?5times per week (lasting at least 10min on each occasion) was linked to a highly significantly benefit for both a decrease in new fatty liver and also improvement of existing fatty liver. PMID- 27255584 TI - Re: Pasquale Rescigno, David Lorente, Diletta Bianchini, et al. Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer. Eur Urol 2016;70:724-31. PMID- 27255585 TI - Improving Survival for Metastatic Castrate-resistant Prostate Cancer: Will Combination Therapy Help Us To Move Forward? PMID- 27255586 TI - Cutaneous larva migrans in a temperate area. PMID- 27255587 TI - Phytochemical profiles and inhibitory effects of Tiger Milk mushroom (Lignosus rhinocerus) extract on ovalbumin-induced airway inflammation in a rodent model of asthma. AB - BACKGROUND: Lignosus rhinocerus (L. rhinocerus), which is known locally as Tiger Milk mushroom, is traditionally used in the treatment of asthma by indigenous communities in Malaysia. However, to date, its efficacy on asthma has not been confirmed by scientific studies and there is also sparse information available on its active constituents. In this study, the volatile constituent of L. rhinocerus hot water extract was investigated using gas chromatography mass spectrometry (GC MS). The potential effects of L. rhinocerus extract for anti-asthmatic activity was further investigated on ovalbumin (OVA)-sensitized asthmatic Sprague Dawley rats. METHODS: Sequential extraction using five solvents (petroleum ether, diethyl ether, hexane, ethyl acetate and methanol) was conducted prior to GC-MS analysis. Male Sprague Dawley rats were divided into the following four groups of five animals each: 1) normal rats, 2) sensitization plus OVA-challenged rats 3) sensitization plus OVA-challenged with L. rhinocerus treatment and 4) sensitization plus OVA-challenged with dexamethasone treatment. The levels of immunoglobulin E (IgE) in the serum and T-helper 2 cytokines, including interleukin (IL)-4, IL-5 and IL-13, in bronchoalveolar lavage fluid (BALF), as well as eosinophil infiltration in the lungs, were investigated. RESULTS: GC-MS analysis revealed the presence of five main groups (alkane, fatty acids, benzene, phenol and dicarboxylic acid) with a total of 18 constituents. Linoleic acid (21.35 %), octadecane (11.82 %) and 2,3-dihydroxypropyl elaidate (10.47 %) were present in high amounts. The extract significantly ameliorated the increase in total IgE in serum and IL-4, IL-5 and IL-13 levels in BALF and also effectively suppressed eosinophils numbers in BALF while attenuating eosinophil infiltrations in the lungs. CONCLUSION: L. rhinocerus hot water extract has the potential to be used as an alternative for the treatment of acute asthma. PMID- 27255588 TI - Enhancing the early home learning environment through a brief group parenting intervention: study protocol for a cluster randomised controlled trial. AB - BACKGROUND: The quality of the home learning environment has a significant influence on children's language and communication skills during the early years with children from disadvantaged families disproportionately affected. This paper describes the protocol and participant baseline characteristics of a community based effectiveness study. It evaluates the effects of 'smalltalk', a brief group parenting intervention (with or without home coaching) on the quality of the early childhood home learning environment. METHODS/DESIGN: The study comprises two cluster randomised controlled superiority trials (one for infants and one for toddlers) designed and conducted in parallel. In 20 local government areas (LGAs) in Victoria, Australia, six locations (clusters) were randomised to one of three conditions: standard care (control); smalltalk group-only program; or smalltalk plus (group program plus home coaching). Programs were delivered to parents experiencing socioeconomic disadvantage through two existing age-based services, the maternal and child health service (infant program, ages 6-12 months), and facilitated playgroups (toddler program, ages 12-36 months). Outcomes were assessed by parent report and direct observation at baseline (0 weeks), post intervention (12 weeks) and follow-up (32 weeks). Primary outcomes were parent verbal responsivity and home activities with child at 32 weeks. Secondary outcomes included parenting confidence, parent wellbeing and children's communication, socio-emotional and general development skills. Analyses will use intention-to-treat random effects ("multilevel") models to account for clustering. RECRUITMENT AND BASELINE DATA: Across the 20 LGAs, 986 parents of infants and 1200 parents of toddlers enrolled and completed baseline measures. Eighty four percent of families demonstrated one or more of the targeted risk factors for poor child development (low income; receives government benefits; single, socially isolated or young parent; culturally or linguistically diverse background). DISCUSSION: This study will provide unique data on the effectiveness of a brief group parenting intervention for enhancing the early home learning environment of young children from disadvantaged families. It will also provide evidence of the extent to which additional one-on-one support is required to achieve change and whether there are greater benefits when delivered in the 1st year of life or later. The program has been designed for scale-up across existing early childhood services if proven effective. TRIAL REGISTRATION: 8 September 2011; ACTRN12611000965909 . PMID- 27255589 TI - Metatarsal head resurfacing arthroplasty in the treatment of hallux rigidus: is it reliable treatment option? AB - BACKGROUND: This study looks at the failure and complications arising secondary to resurfacing and hemi-arthroplasty done at the metatarsal head in patients with hallux rigidus. Our report includes a review of the relevant literature to verify the validity of our techniques. MATERIALS AND METHODS: We performed metatarsal head resurfacing with hemi-arthroplasty using the HemiCap((r)), on 12 patients with hallux rigidus between the dates of March 2010 and October 2013. The mean follow-up period was 22.3 months (range 12-54). All patients were clinically and radiologically evaluated according to the American Orthopedics Foot and Ankle Society (AOFAS) functional scale and the Coughlin and Shurnas classification. RESULTS: The recorded mean AOFAS score showed an increase from the preoperative score of 49.2 +/- 13.1 to a postoperative follow-up score of 80.8 +/- 13.1 (p < 0.001). Pain scores also showed an improvement from 16.5 +/- 7.1 points preoperatively to 32.5 +/- 6.9 points during the postoperative follow-up (p < 0.001). The mean function score improved from 17.7 +/- 7.6 points preoperatively to 33.2 +/- 7.6 points during the final postoperative follow-up (p < 0.001). Furthermore, the mean range of motion improved from 16.3 +/- 4.8 degrees preoperatively to 45.4 +/- 13.2 degrees postoperatively (p < 0.001). Three patients (25 %) reported pain at rest. Surgical revision was done on these patients who have significant pain that limited their range of motion. CONCLUSION: Favorable outcomes were achieved by performing minimal bone resection which also helps maintain metatarso-phalangeal joint function through metatarsal head resurfacing arthroplasty. We expect the failure rates to decrease with the advancements of surgical techniques. Selecting the appropriate patient populous in the application of the technique is crucial in attaining successful clinical results. PMID- 27255590 TI - Safety, efficacy and repeatability of a novel house dust mite allergen challenge technique in the Fraunhofer allergen challenge chamber. AB - BACKGROUND: Efficacy testing of immunotherapy in field studies is often hampered by variation of airborne allergens. Standardized allergen exposure in challenge chamber settings might be an alternative. Therefore, we developed a universal technique to create an atmosphere loaded with allergen particles of adjustable size from aqueous solutions of licensed allergen extracts. OBJECTIVE: The aim of this study was to apply this technique and test the safety and efficacy of challenges with house dust mite (HDM) allergen in the Fraunhofer allergen challenge chamber. METHODS: Aerosol particles carrying HDM allergen were produced by spray-drying of an aqueous solution containing HDM allergen and lactose. In a monocenter, placebo-controlled, single-blind, dose-escalation pilot study, 18 subjects with perennial allergic rhinitis and sensitization to HDM were exposed to HDM allergen for 4 h at either 250, 500, 1000 SQE/m3 or lactose alone (0 SQE/m3 ) 7 days apart. The dose of 500 SQE/m3 was repeated to investigate reproducibility. Total nasal symptom score (TNSS) was the primary endpoint. RESULTS: Exposure to HDM increased TNSS (mean +/- SD) to 3.4 +/- 1.8, 3.3 +/- 2.1, and 3.6 +/- 2.0 at 250, 500 and 1000 SQE/m3 , respectively, while lactose alone did not change TNSS (0.7 +/- 0.6). The results were reproducible at 500 SQE/m3 . Pulmonary function and adverse event frequency did not change with escalation of allergen dose. CONCLUSION: This HDM allergen particle generation is safe, specific and reproducible and can therefore be used for efficacy testing of immunotherapy and for basic clinical research. PMID- 27255592 TI - Retraction Note: Changes in the electron paramagnetic resonance spectra of albumin-associated spin-labeled stearic acid as a diagnostic parameter of colorectal cancer. PMID- 27255591 TI - Evaluating Quality and Adequacy of Gastrointestinal Samples Collected using Reusable or Disposable Forceps. AB - BACKGROUND: Sample quality of gastrointestinal endoscopic biopsies is of paramount importance for accurate histological diagnosis. Many veterinary practices use reusable forceps as a result of perceived decreased cost. With reusable forceps, it remains unknown whether sample quality declines with repeated use and becomes inferior to single-use forceps and is therefore more or less cost effective than single-use forceps. HYPOTHESIS/OBJECTIVES: The study hypothesis was that reusable forceps sample quality would deteriorate after repeated use as compared to single-use forceps. ANIMALS: Sixty-five dogs undergoing gastrointestinal endoscopy for diagnostic investigations at the Hospital for Small Animals, Edinburgh University. METHOD: A prospective, pathologist-blinded study comparing single-use and reusable alligator standard cup biopsy forceps (Olympus 2.0 mm 1550 mm) with 5 randomized reusable forceps. Sample quality (stomach, duodenum, ileum, and colon) was assessed by a single pathologist using the WSAVA guidelines. RESULTS: There was no difference in the adequacy, depth, villi number, or crush artifact in the 4 intestinal areas between forceps type with at least 10, and up to 15, repeated uses of the reusable forceps. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrates that reusable cup biopsy forceps provide equivalent biopsy quality after repeated uses to single-use forceps and are cost effective at 10-case use. PMID- 27255593 TI - Secukinumab: A Review in Ankylosing Spondylitis. AB - Secukinumab (Cosentyx((r))) is a fully human monoclonal antibody against the proinflammatory cytokine interleukin-17A. It is the first drug in its class to be approved for use in patients with active ankylosing spondylitis (AS). This article reviews the efficacy and tolerability of secukinumab in this indication and briefly summarizes its pharmacology. In ongoing phase III trials, 16 weeks' treatment with subcutaneous secukinumab 150 mg was effective in terms of improving the clinical signs and symptoms of disease and health-related quality of life in patients with AS, with these improvements maintained during longer term (up to 2 years) treatment. In subgroup analyses, secukinumab was effective both in tumour necrosis factor (TNF) inhibitor-naive patients and in patients intolerant of or refractory to TNF inhibitors. Secukinumab was generally well tolerated, with a tolerability profile consistent with that seen previously in patients with plaque psoriasis. In the absence of head-to-head trials, the position of secukinumab with respect to TNF inhibitors remains to be fully determined. Nevertheless, secukinumab is an effective and generally well tolerated treatment option for patients with AS. PMID- 27255594 TI - Is there a link between dizziness and vision? A systematic review. AB - PURPOSE: The aim of this study was to systematically review the literature to investigate the link (if any) between vision and dizziness. METHODS: Medline, CINAHL, AMED, Web of Science and The Cochrane Library were searched with keywords chosen to find articles which investigated the causes of dizziness and considered vision as a possible trigger. Citation chaining of all included papers was performed in addition to the hand searching of all reference lists. Unpublished literature was identified using www.opengrey.eu. The review considered studies involving adults which link, measure or attempt to improve any aspect of vision in relation to dizziness. RESULTS: Nine thousand six hundred and eighty one possible references were found, and the abstracts were screened independently by two reviewers to determine if they should be included in the study. Thirteen papers were found which investigated whether dizziness was linked to an assessment of vision. Visual impairment measures were crude and typically self report, or Snellen visual acuity with little or no measurement details. Five studies found an independent link between dizziness and vision, five found a weak association (typically finding a link when univariate analyses were used, but not when multivariate analyses were used), and three found no association. Studies finding a strong link were usually cross-sectional with a large study population whereas those finding a weak association had relatively small numbers of participants. Studies which did not find an association used a broad definition of dizziness that included the term light-headedness, an unreliable Rosenbaum near visual acuity chart or an unusual categorisation of visual acuity. CONCLUSIONS: This review suggests that dizziness (although likely not 'light headedness') is linked with poor vision although further studies using more appropriate measures of vision are recommended. PMID- 27255595 TI - The effect of middle turbinate resection on topical drug distribution into the paranasal sinuses. AB - BACKGROUND: During sinus surgery, partial or complete resection of the middle turbinate (MT) is sometimes necessary because of polypoid changes or demineralization. Topical drug delivery to the paranasal sinuses is an integral component in managing chronic rhinosinusitis (CRS) with and without nasal polyposis. The purpose of this study was to examine the role of the MT and MT resection in topical drug distribution into the sinuses via nebulization. We report on a novel technique of quantitatively evaluating the delivery of nebulized dye in cadavers. METHODS: Endoscopic sinus surgery was performed on 5 fresh cadavers. Complementary colored dyes mixed with saline were successively nebulized using the following protocol: (1) fluorescein prior to MT resection; (2) brilliant green following partial MT resection; and (3) methylene blue following total MT resection. Photodocumentation of the sinuses was performed following each nebulization and standardized photoanalysis was performed. RESULTS: Successive nebulizations with fluorescein, brilliant green, and methylene blue produced a complementary staining pattern that provided an easy side-by-side analysis of the extent of mucosal staining. Dye delivery to the frontal and sphenoid sinuses significantly increased following partial resection of the MT (p = 0.013 and p = 0.0027, respectively) and complete resection of the MT (p = 0.027 and p = 0.027, respectively). Following complete MTR, dye delivery to the maxillary sinus significantly increased compared to baseline (MT intact) (p = 0.0027). CONCLUSION: Resection of the MT appears to have a significant effect on nebulized drug delivery into the frontal, maxillary, and sphenoid sinuses. Future prospective studies will help delineate the clinical relevance of this effect. PMID- 27255596 TI - Regulation of group 2 innate lymphoid cells. AB - Group 2 innate lymphoid cells (ILC2) exert critical roles in type 2 immune responses, epithelial repair at mucosal tissues and metabolic homeostasis. ILC2 rapidly provide large amounts of type 2 signature cytokines, thereby driving type 2 immune responses such as the defense against helminths. However, if deregulated, ILC2 facilitate tissue fibrosis and trigger unwanted type 2 immunopathologies such as allergies, asthma and atopic dermatitis. Therefore, ILC2 need to be tightly regulated and we are just beginning to understand which mediators activate or inhibit this rare but important cell population. In this review, we summarize current knowledge about positive and negative regulation of ILC2 and discuss its immunological consequences. PMID- 27255597 TI - Improved Accuracy of Automated Estimation of Cardiac Output Using Circulation Time in Patients with Heart Failure. AB - BACKGROUND: Lung-to-finger circulation time of oxygenated blood during nocturnal periodic breathing in heart failure patients measured using polysomnography correlates negatively with cardiac function but possesses limited accuracy for cardiac output (CO) estimation. METHODS AND RESULTS: CO was recalculated from lung-to-finger circulation time using a multivariable linear model with information on age and average overnight heart rate in 25 patients who underwent evaluation of heart failure. The multivariable model decreased the percentage error to 22.3% relative to invasive CO measured during cardiac catheterization. CONCLUSIONS: This improved automated noninvasive CO estimation using multiple variables meets a recently proposed performance criterion for clinical acceptability of noninvasive CO estimation, and compares very favorably with other available methods. PMID- 27255598 TI - Poly(ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors Reduce Reactive Gliosis and Improve Angiostatin Levels in Retina of Diabetic Rats. AB - Diabetic retinopathy (DR) is a multifactorial disease characterized by reactive gliosis and disbalance of angiogenesis regulators, contributing to endothelial dysfunction and microvascular complications. This study was organized to elucidate whether poly(ADP-ribose) polymerase-1 (PARP-1) inhibition could attenuate diabetes-induced damage to macroglia and correct angiogenic disbalance in diabetic rat retina. After 8 weeks of streptozotocin (STZ)-induced diabetes, Wistar male rats were treated with PARP-1 inhibitors, nicotinamide (NAm) or 3 aminobenzamide (3-AB) (100 and 30 mg/kg/daily i.p., respectively), for 14 days. After the 10-weeks experiment period, retinas were undergone an immunohistochemical staining for glial fibrillary acidic protein (GFAP), while western blots were performed to evaluate effects of PAPR-1 inhibitors on the levels of PARP-1, poly(ADP-ribosyl)ated proteins (PARs), GFAP, and angiostatin isoforms. Diabetes induced significant up-regulation and activation of retinal PARP-1, reactive gliosis development, and GFAP overexpression compared to non diabetic control. Moreover, extensive fragmentation of both PARP-1 and GFAP (hallmarks of apoptosis and macroglia reactivation, respectively) in diabetic retina was also observed. Levels of angiostatin isoforms were dramatically decreased in diabetic retina, sustaining aberrant pro-angiogenic condition. Both NAm and 3-AB markedly attenuated damage to macroglia, evidenced by down regulation of PARP-1, PARs and total GFAP compared to diabetic non-treated group. PARP-1-inhibitory therapy prevented formation of PARP-1 and GFAP cleavage-derived products. In retinas of anti-PARP-treated diabetic animals, partial restoration of angiostatin's levels was shown. Therefore, PARP-1 inhibitors counteract diabetes-induced injuries and manifest retinoprotective effects, including attenuation of reactive gliosis and improvement of angiogenic status, thus, such agents could be considered as promising candidates for DR management. PMID- 27255599 TI - Taurine Pretreatment Prevents Isoflurane-Induced Cognitive Impairment by Inhibiting ER Stress-Mediated Activation of Apoptosis Pathways in the Hippocampus in Aged Rats. AB - Isoflurane, a commonly used inhalation anesthetic, may induce neurocognitive deficits, especially in elderly patients after surgery. Recent study demonstrated that isoflurane caused endoplasmic reticulum (ER) stress and subsequent neuronal apoptosis in the brain, contributing to cognitive deficits. Taurine, a major intracellular free amino acid, has been shown to inhibit ER stress and neuronal apoptosis in several neurological disorders. Here, we examined whether taurine can prevent isoflurane-induced ER stress and cognitive impairment in aged rats. Thirty minutes prior to a 4-h 1.3 % isoflurane exposure, aged rats were treated with vehicle or taurine at low, middle and high doses. Aged rats without any treatment served as control. The brains were harvested 6 h after isoflurane exposure for molecular measurements, and behavioral study was performed 2 weeks later. Compared with control, isoflurane increased expression of hippocampal ER stress biomarkers including glucose-regulated protein 78, phosphorylated (P-) inositol-requiring enzyme 1, P-eukaryotic initiation factor 2-alpha (EIF2alpha), activating transcription factor 4 (ATF-4), cleaved ATF-6 and C/EBP homologous protein, along with activation of apoptosis pathways as indicated by decreased B cell lymphoma 2 (BCL-2)/BCL2-associated X protein, increased expressions of cytochrome-c and cleaved caspase-3. Taurine pretreatment dose-dependently inhibited isoflurane-induced increase in expression of ER stress biomarkers except for P-EIF2alpha and ATF-4, and reversed isoflurane-induced changes in apoptosis-related proteins. Moreover, isoflurane caused spatial working memory deficits in aged rats, which were prevented by taurine pretreatment. The results indicate that taurine pretreatment prevents anesthetic isoflurane-induced cognitive impairment by inhibiting ER stress-mediated activation of apoptosis pathways in the hippocampus in aged rats. PMID- 27255600 TI - Cognition Enhancing Activity of Sulforaphane Against Scopolamine Induced Cognitive Impairment in Zebra Fish (Danio rerio). AB - Several epidemiological studies have shown that consumption of large quantities of vegetables especially cruciferous vegetables (Broccoli and Brussels sprouts) can protect against chronic diseases. Sulforaphane, an isothiocynate found in cruciferous vegetables has been demonstrated to have neuroprotective effects in several experimental paradigms. This study was undertaken to examine the effect of sulforaphane on cognitive impairment in zebra fish model using a novel method of fear conditioning. Initially, the normal behaviour of zebra fishes was studied in light-dark tank for 10 min daily for 10 days. Fishes were then divided into seven groups of twelve in each. Group I served as normal, group II served as fear conditioned control, group III and group IV were sulforaphane (25 uM/L) and piracetam (200 mg/L) treated respectively. Group V served as scopolamine (400 uM/L) induced memory impairment fishes. Group VI and VII were sulforaphane (25 uM/L) and piracetam (200 mg/L) treated scopolamine induced memory impairment groups respectively. In normal behavioural analysis, fishes preferred to stay in dark compartment. The average number of entries into the dark and time spent in dark were significantly more. Fishes in group II to VII were individually subjected to fear conditioning passive avoidance task and evaluated for learned task memory. It was observed that the average number of entries into dark and time spent in dark were significantly decreased. After exposure to respective treatment fishes in group III to VII were subjected to cognitive evaluation. There was no significant difference in cognition of group III and IV fishes exposed to sulforaphane and piracetam alone respectively. Fishes exposed to scopolamine showed a significant cognitive impairment. Sulforaphane exposure prior to scopolamine significantly retained the memory of learned task. These findings suggest that sulforaphane might be a promising therapeutic agent for cognitive enhancement in Alzheimer's disease. PMID- 27255601 TI - Arecoline Induces Neurotoxicity to PC12 Cells: Involvement in ER Stress and Disturbance of Endogenous H2S Generation. AB - Arecoline is a major alkaloid of areca nut and has been effect on central nervous system. Although arecoline-induced neurotoxicity has been reported, the possible underlying neurotoxic mechanisms have not yet been elucidated. Increasing evidences have shown that both excessive endoplasmic reticulum (ER) stress and disturbance of hydrogen sulfide (H2S) production are involved in the pathophysiology of numerous neurodegenerative diseases. Here, the purpose of present study was to verify whether ER stress and the disturbance of endogenous H2S generation are also involved in arecoline-caused neurotoxicity. We found that treatment of PC12 cells with arecoline induced the down-regulation of cells viability and up-regulation of apoptosis and the activity of caspase-3, indicating the neurotoxic role of arecoline to PC12 cells. In addition, arecoline also increased the expression of Bax (pro-apoptotic protein) and attenuated the expression of Bcl-2 (anti-apoptotic protein) in PC12 cells. Simultaneously, arecoline caused excessive ER stress in PC12 cells, as evidenced by the up regulations of Glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), and Cleaved caspase-12 expressions. Notably, the level of H2S in the culture supernatant and the expressions of cystathionine beta-synthase and 3-mercaptopyruvate sulfurtransferase (two major enzymes for endogenous H2S generation in PC12 cells) were also reduced by arecoline treatment. These results indicate that arecoline-caused neurotoxicity to PC12 cells is involved in ER stress and disturbance of endogenous H2S generation and suggest that the modulation of ER stress and endogenous H2S generation may be potential therapeutic approach in treatment of arecoline-caused neurotoxicity. PMID- 27255602 TI - RNA Interference Silencing of Glycogen Synthase Kinase 3beta Inhibites Tau Phosphorylation in Mice with Alzheimer Disease. AB - To explore the effect of glycogen synthase kinase 3beta (GSK-3beta) silencing on Tau-5 phosphorylation in mice suffering Alzheimer disease (AD). GSK-3beta was firstly silenced in human neuroblastoma SH-SY5Y cells using special lentivirus (LV) and the content of Tau (A-12), p-Tau (Ser396) and p-Tau (PHF-6) proteins. GSK-3beta was also silenced in APP/PS1 mouse model of AD mice, which were divided into three groups (n = 10): AD, vehicle, and LV group. Ten C57 mice were used as control. The memory ability of mice was tested by square water maze, and the morphological changes of hippocampus and neuron death were analyzed by haematoxylin-eosin staining. Moreover, the levels of Tau and phosphorylated Tau (p-Tau) were detected by western blotting and immunohistochemistry, respectively. The lentivirus-mediated GSK-3beta silencing system was successfully developed and silencing GSK-3beta at the cellular level reduced Tau phosphorylation obviously. Moreover, GSK-3beta silence significantly improved the memory ability of AD mice in LV group compared with AD group (P < 0.05) according to the latency periods and error numbers. As for the hippocampus morphology and neuron death, no significant change was observed between LV group and normal control. Immunohistochemical detection and western blotting revealed that the levels of Tau and p-Tau were significantly down-regulated after GSK-3beta silence. Silencing GSK-3beta may have a positive effect on inhibiting the pathologic progression of AD through down-regulating the level of p-Tau. PMID- 27255604 TI - Effects of aortic root motion on wall stress in the Marfan aorta before and after personalised aortic root support (PEARS) surgery. AB - Aortic root motion was previously identified as a risk factor for aortic dissection due to increased longitudinal stresses in the ascending aorta. The aim of this study was to investigate the effects of aortic root motion on wall stress and strain in the ascending aorta and evaluate changes before and after implantation of personalised external aortic root support (PEARS). Finite element (FE) models of the aortic root and thoracic aorta were developed using patient specific geometries reconstructed from pre- and post-PEARS cardiovascular magnetic resonance (CMR) images in three Marfan patients. The wall and PEARS materials were assumed to be isotropic, incompressible and linearly elastic. A static load on the inner wall corresponding to the patients' pulse pressure was applied. Cardiovascular MR cine images were used to quantify aortic root motion, which was imposed at the aortic root boundary of the FE model, with zero displacement constraints at the distal ends of the aortic branches and descending aorta. Measurements of the systolic downward motion of the aortic root revealed a significant reduction in the axial displacement in all three patients post-PEARS compared with its pre-PEARS counterparts. Higher longitudinal stresses were observed in the ascending aorta when compared with models without the root motion. Implantation of PEARS reduced the longitudinal stresses in the ascending aorta by up to 52%. In contrast, the circumferential stresses at the interface between the supported and unsupported aorta were increase by up to 82%. However, all peak stresses were less than half the known yield stress for the dilated thoracic aorta. PMID- 27255603 TI - Deletion of Brg1 causes abnormal hair cell planer polarity, hair cell anchorage, and scar formation in mouse cochlea. AB - Hair cells (HCs) are mechanosensors that play crucial roles in perceiving sound, acceleration, and fluid motion. The precise architecture of the auditory epithelium and its repair after HC loss is indispensable to the function of organ of Corti (OC). In this study, we showed that Brg1 was highly expressed in auditory HCs. Specific deletion of Brg1 in postnatal HCs resulted in rapid HC degeneration and profound deafness in mice. Further experiments showed that cell intrinsic polarity of HCs was abolished, docking of outer hair cells (OHCs) by Deiter's cells (DCs) failed, and scar formation in the reticular lamina was deficient. We demonstrated that Brg1 ablation disrupted the Galphai/Insc/LGN and aPKC asymmetric distributions, without overt effects on the core planer cell polarity (PCP) pathway. We also demonstrated that Brg1-deficient HCs underwent apoptosis, and that leakage in the reticular lamina caused by deficient scar formation shifted the mode of OHC death from apoptosis to necrosis. Together, these data demonstrated a requirement for Brg1 activity in HC development and suggested a role for Brg1 in the proper cellular structure formation of HCs. PMID- 27255605 TI - Optimizing nutrient channel spacing and revisiting TGF-beta in large engineered cartilage constructs. AB - Cartilage tissue engineering is a promising approach to treat osteoarthritis. However, current techniques produce tissues too small for clinical relevance. Increasingly close-packed channels have helped overcome nutrient transport limitations in centimeter-sized chondrocyte-agarose constructs, yet optimal channel spacings to recapitulate native cartilage compositional and mechanical properties in constructs this large have not been identified. Transient active TGF-beta treatment consistently reproduces native compressive Young's modulus (EY) and glycosaminoglycan (GAG) content in constructs, but standard dosages of 10ng/mL exacerbate matrix heterogeneity. To ultimately produce articular layer sized constructs, we must first optimize channel spacing and investigate the role of TGF-beta in the utility of channels. We cultured ?10mm constructs with 0, 12, 19, or 27 nutrient channels (?1mm) for 6-8 weeks with 0, 1, or 10ng/mL TGF-beta; subsequently we analyzed them mechanically, biochemically, and histologically. Constructs with 12 or 19 channels grew the most favorably, reaching EY=344+/ 113kPa and GAG and collagen contents of 10.8+/-1.2% and 2.2+/-0.2% of construct wet weight, respectively. Constructs with 27 channels had significantly less deposited GAG than other groups. Channeled constructs given 1 or 10ng/mL TGF-beta developed similar properties. Without TGF-beta, constructs with 0 or 12 channels exhibited properties that were indistinguishable, and lower than TGF-beta supplemented constructs. Taken together, these results emphasize that nutrient channels are effective only in the presence of TGF-beta, and indicate that spacings equivalent to 12 channels in ?10mm constructs can be employed in articular-layer-sized constructs with reduced dosages of TGF-beta. PMID- 27255606 TI - Can a linear combination of gait principal component vectors identify hip OA stages? AB - Hip osteoarthritis (OA) has been shown to affect gait patterns of lower extremities. However, until now, no specific identifying gait characteristics for the various disease stages of hip OA have emerged. The present study addresses the following questions: (1) does a vector-based principal component analysis (PCA) discriminate between various disease stages? And, is this analysis more robust than using discrete gait variables? (2) Does the elimination of differences in walking speed affect the discriminatory robustness of a vector based PCA? De-identified data sets of forty-five unilateral hip OA patients with varying disease stages and twenty-three age-matched, healthy control subjects were obtained from an available repository. PCA was performed on trial matrices consisting of all external joint moments and sagittal joint angles of one full gait cycle. Group differences in sagittal angles, external moments and the linear combination of PC vectors were investigated using spatial parameter mapping (SPM), a statistical vector field test. Several individual gait variables (i.e. joint moments or angles) demonstrated differences between healthy and moderately and/or severely affected subjects. Only the hip adduction moment could discriminate between the healthy and the early-stage OA group. There was no variable that could distinguish between all OA disease stages. In contrast, the linear combination of PC vectors demonstrated significant group differences between all stages of osteoarthritis; furthermore, these group differences stayed significant when matched speeds were input to the model. PMID- 27255607 TI - The Design of the Internet's Architecture by the Internet Engineering Task Force (IETF) and Human Rights. AB - The debate on whether and how the Internet can protect and foster human rights has become a defining issue of our time. This debate often focuses on Internet governance from a regulatory perspective, underestimating the influence and power of the governance of the Internet's architecture. The technical decisions made by Internet Standard Developing Organisations (SDOs) that build and maintain the technical infrastructure of the Internet influences how information flows. They rearrange the shape of the technically mediated public sphere, including which rights it protects and which practices it enables. In this article, we contribute to the debate on SDOs' ethical responsibility to bring their work in line with human rights. We defend three theses. First, SDOs' work is inherently political. Second, the Internet Engineering Task Force (IETF), one of the most influential SDOs, has a moral obligation to ensure its work is coherent with, and fosters, human rights. Third, the IETF should enable the actualisation of human rights through the protocols and standards it designs by implementing a responsibility by-design approach to engineering. We conclude by presenting some initial recommendations on how to ensure that work carried out by the IETF may enable human rights. PMID- 27255608 TI - Caregiving burden and gain among adult-child caregivers caring for parents with dementia in China: the partial mediating role of reciprocal filial piety. AB - BACKGROUND: The majority of the family caregivers are adult children in China. The aim of this study was to examine the mediating role of reciprocal filial piety (RFP) between the care recipient's behavioral and psychological symptoms of dementia (BPSD) and the caregiver's burden or gain among adult-child caregivers caring for parents with dementia in China. METHODS: Using Kramer's caregiver adaptation model as the research framework, a cross-sectional survey collected data from 401 adult-child caregivers caring for parents with dementia from hospitals in China. RESULTS: Results of the regression analysis revealed that after adjusting for covariates, the regression coefficient between care recipient's BPSD and caregiver burden reduced from c = 1.01 to c' = 0.91 when controlling for RFP. Using the bootstrap approach, the estimated indirect effect through RFP between care recipient's BPSD and caregiver burden was 0.11 (95% CI: 0.03, 0.20). The mediation proportion was 11%. The absolute value of the regression coefficient between care recipient's BPSD and caregiver gain reduced from c = -0.75 to c' = -0.63 when controlling for RFP. The bootstrapped estimate of the indirect effect through RFP between care recipient's BPSD and caregiver gain was -0.12 (95% CI: -0.18, -0.07). The mediation proportion was 12%. CONCLUSIONS: The findings suggest that the effect of care recipient's BPSD on caregiver's burden/gain may be related to the level of RFP among adult-child caregivers in China. PMID- 27255609 TI - Cortisol during human fetal life: Characterization of a method for processing small quantities of newborn hair from 26 to 42 weeks gestation. AB - OBJECTIVE: Fetal cortisol may be reflected in hair collected shortly after birth. The objective of this study was to determine the range of human fetal hair cortisol concentrations (HCC) in live-born neonates using an approach for processing small quantities of hair. MATERIALS AND METHODS: Hair was cut on the day of birth from neonates and their mothers, born between 26 and 42 weeks gestational age (GA). HCC was determined by enzyme immunoassay. Maternal sociodemographics and birth data were collected. T-tests, ANOVA, Pearson correlation, and Wilcoxon Signed Rank test were used as appropriate. RESULTS: Ninety maternal and neonatal hair samples were cut from 79 term (T) and 11 preterm (PT) delivered pregnancies. All samples weighed >=2.5 mg. Fetal HCC correlated with GA (r = .25, p = .02) and birth weight (r = .25, p = .03) and was lower in PT (4.3 +/- .3 LN pg/mg) than T (5.3 +/- .1, LN pg/mg, p < .001) neonates. No significant relationships were seen between fetal HCC and maternal characteristics or maternal HCC. Fetal HCC was significantly higher than maternal HCC. CONCLUSION: Fetal cortisol exposure was determined using this approach for processing small amounts of hair. Preterm neonates have significantly lower HCC than term neonates and fetal HCC is associated with GA at delivery and birth weight. Fetal HCC is significantly higher than maternal HCC cut on the same day. These data provide novel information on the intrauterine fetal cortisol environment. PMID- 27255610 TI - Endoplasmic Reticulum Calcium Regulates Epidermal Barrier Response and Desmosomal Structure. AB - Ca(2+) fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, and epidermal barrier homeostasis. We previously showed that intracellular Ca(2+) stores constitute a major portion of the calcium gradient especially in the stratum granulosum. Loss of the calcium gradient triggers epidermal barrier homeostatic responses. In this report, using unfixed ex vivo epidermis and human epidermal equivalents we show that endoplasmic reticulum (ER) Ca(2+) is released in response to barrier perturbation, and that this release constitutes the major shift in epidermal Ca(2+) seen after barrier perturbation. We find that ER Ca(2+) release correlates with a transient increase in extracellular Ca(2+). Lastly, we show that ER calcium release resulting from barrier perturbation triggers transient desmosomal remodeling, seen as an increase in extracellular space and a loss of the desmosomal intercellular midline. Topical application of thapsigargin, which inhibits the ER Ca(2+) ATPase activity without compromising barrier integrity, also leads to desmosomal remodeling and loss of the midline structure. These experiments establish the ER Ca(2+) store as a master regulator of the Ca(2+) gradient response to epidermal barrier perturbation, and suggest that ER Ca(2+) homeostasis also modulates normal desmosomal reorganization, both at rest and after acute barrier perturbation. PMID- 27255612 TI - How Regrouping Alerts in Computerized Physician Order Entry Layout Influences Physicians' Prescription Behavior: Results of a Crossover Randomized Trial. AB - BACKGROUND: As demonstrated in several publications, low positive predictive value alerts in computerized physician order entry (CPOE) induce fatigue and may interrupt physicians unnecessarily during prescription of medication. Although it is difficult to increase the consideration of medical alerts by physician through an improvement of their predictive value, another approach consists to act on the way they are presented. The interruption management model inspired us to propose an alternative alert display strategy of regrouping the alerts in the screen layout, as a possible solution for reducing the interruption in physicians' workflow. OBJECTIVE: In this study, we compared 2 CPOE designs based on a particular alert presentation strategy: one design involved regrouping the alerts in a single place on the screen, and in the other, the alerts were located next to the triggering information. Our objective was to evaluate experimentally whether the new design led to fewer interruptions in workflow and if it affected alert handling. METHODS: The 2 CPOE designs were compared in a controlled crossover randomized trial. All interactions with the system and eye movements were stored for quantitative analysis. RESULTS: The study involved a group of 22 users consisting of physicians and medical students who solved medical scenarios containing prescription tasks. Scenario completion time was shorter when the alerts were regrouped (mean 117.29 seconds, SD 36.68) than when disseminated on the screen (mean 145.58 seconds, SD 75.07; P=.045). Eye tracking revealed that physicians fixated longer on alerts in the classic design (mean 119.71 seconds, SD 76.77) than in the centralized alert design (mean 70.58 seconds, SD 33.53; P=.001). Visual switches between prescription and alert areas, indicating interruption, were reduced with centralized alerts (mean 41.29, SD 21.26) compared with the classic design (mean 57.81, SD 35.97; P=.04). Prescription behavior (ie, prescription changes after alerting), however, did not change significantly between the 2 strategies of display. The After-Scenario Questionnaire (ASQ) that was filled out after each scenario showed that overall satisfaction was significantly rated lower when alerts were regrouped (mean 4.37, SD 1.23) than when displayed next to the triggering information (mean 5.32, SD 0.94; P=.02). CONCLUSIONS: Centralization of alerts in a table might be a way to motivate physicians to manage alerts more actively, in a meaningful way, rather than just being interrupted by them. Our study could not provide clear recommendations yet, but provides objective data through a cognitive psychological approach. Future tests should work on standardized scenarios that would enable to not only measure physicians' behavior (visual fixations and handling of alerts) but also validate those actions using clinical criteria. PMID- 27255611 TI - Nutrient shortage triggers the hexosamine biosynthetic pathway via the GCN2-ATF4 signalling pathway. AB - The hexosamine biosynthetic pathway (HBP) is a nutrient-sensing metabolic pathway that produces the activated amino sugar UDP-N-acetylglucosamine, a critical substrate for protein glycosylation. Despite its biological significance, little is known about the regulation of HBP flux during nutrient limitation. Here, we report that amino acid or glucose shortage increase GFAT1 production, the first and rate-limiting enzyme of the HBP. GFAT1 is a transcriptional target of the activating transcription factor 4 (ATF4) induced by the GCN2-eIF2alpha signalling pathway. The increased production of GFAT1 stimulates HBP flux and results in an increase in O-linked beta-N-acetylglucosamine protein modifications. Taken together, these findings demonstrate that ATF4 provides a link between nutritional stress and the HBP for the regulation of the O-GlcNAcylation dependent cellular signalling. PMID- 27255613 TI - Corrigendum: Diverse human extracellular RNAs are widely detected in human plasma. PMID- 27255614 TI - Extra fees for uninsured services. PMID- 27255615 TI - [Frais accessoires]. PMID- 27255616 TI - Social accountability: Nunavut perspective. PMID- 27255617 TI - Greener medical homes: Environmental responsibility in family medicine. PMID- 27255618 TI - Ecology of family physicians' research engagement. PMID- 27255619 TI - [Responsabilite sociale: Perspective du Nunavut]. PMID- 27255620 TI - Update on the new 9-valent vaccine for human papillomavirus prevention. AB - OBJECTIVE: To provide family physicians with information on the efficacy, safety, public health effects, and cost-effectiveness of the 9-valent human papillomavirus (HPV) vaccine. QUALITY OF EVIDENCE: Relevant publications in PubMed up to May 2015 were reviewed and analyzed. Most evidence cited is level I (randomized controlled trials and meta-analyses) or level II (cross-sectional, case-control, and epidemiologic studies). Government reports and recommendations are also referenced. MAIN MESSAGE: The 9-valent HPV vaccine, which protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, is safe and effective and will further reduce the incidence of HPV infection, as well as HPV-related cancers. It can also indirectly protect unvaccinated individuals through herd immunity. With an effective vaccination program, most cervical cancers can be prevented. Analyses show that the cost-effectiveness of the 9-valent HPV vaccine in female patients is comparable to the original quadrivalent HPV vaccine (which protects against HPV types 6, 11, 16, and 18) currently in use. However, the usefulness of vaccinating male patients with the 9-valent HPV vaccine needs further investigation. CONCLUSION: The 9-valent HPV vaccine offers more protection against HPV than the quadrivalent HPV vaccine does and is as safe. Analysis of cost-effectiveness favours its use, at least in adolescent girls. Therefore, physicians should recommend the 9-valent HPV vaccine to patients instead of the quadrivalent HPV vaccine. PMID- 27255621 TI - Acyclovir for herpetic gingivostomatitis in children. AB - QUESTION: Every year I see preschool children with gingivostomatitis. There seems to be quite a substantial burden of illness with this condition. Because it is caused by herpes simplex virus type 1, should I prescribe antiherpetic therapy with oral acyclovir? ANSWER: While most children with primary gingivostomatitis will be asymptomatic, some will experience considerable pain and discomfort and are at risk of dehydration. There are no large, well designed studies to clearly determine appropriate therapy for all children. Based on a single randomized study, treatment should be started only within the first 72 hours of symptom onset if substantial pain or dehydration are documented. PMID- 27255622 TI - Deep tissue infection of the perineum: Case report and literature review of Fournier gangrene. PMID- 27255623 TI - Choosing Wisely Canada recommendations: Interview with Dr Jean Pierre Arseneau. PMID- 27255625 TI - Pharmacologic management of COPD: Breadth of products for encouraging a breath of air. PMID- 27255624 TI - Is less more with isotretinoin and acne? PMID- 27255626 TI - What's sewn in. PMID- 27255627 TI - Beyond frozen ground: Climate change and health. PMID- 27255629 TI - [Les medecins d'urgence repondent aux besoins de la communaute]. PMID- 27255628 TI - Feedback in family medicine training. PMID- 27255630 TI - Emergency physicians respond to community needs. PMID- 27255631 TI - [Des centres de medecine plus ecologiques: Responsabilite environnementale en medecine familiale]. PMID- 27255632 TI - [L'ecologie de l'engagement des medecins de famille dans la recherche]. PMID- 27255633 TI - [Prise en charge pharmacologique de la BPCO: Un eventail de produits pour insuffler une bouffee d'air]. PMID- 27255634 TI - Providing continuity of care to a specific population: Attracting new family physicians. AB - OBJECTIVE: To analyze the factors that influence newly licensed family physicians in their decision to provide continuity of care to a specific primary care population. DESIGN: Mixed-methods study that included a self-administered online questionnaire for family physicians followed by individual interviews. SETTING: Monteregie, the second-most populated region of Quebec, with rural and urban areas. PARTICIPANTS: All family physicians with 10 or fewer years of work experience who were practising in Monteregie were contacted (366 physicians). Of this group, 118 completed the online questionnaire (response rate of 32.2%). Of the respondents, 10 physicians with varied continuity of care profiles were selected for individual interviews. MAIN OUTCOME MEASURES: The percentage of work time spent on continuity of care analyzed in conjunction with factors that support or present barriers to continuity of care at the contextual and organizational levels and for family physicians and patients. RESULTS: The main factors that facilitate continuity of care are the physician-patient relationship, interest in clinical continuity of care activities, positive role models, working alongside a nurse, and adequate access to resources, specifically mental health resources. The main barriers are the scope of administrative duties, interest in a comprehensive practice, a negative experience of continuity of care during training, a sense of inadequacy with respect to continuity of care, a heavy case load, and a lack of support in the first years of practice. CONCLUSION: Possible ways to encourage newly licensed family physicians to provide continuity of care to a specific population are offered. Areas for improvement include medical training, administrative support, and human resources. PMID- 27255635 TI - [Au-dela du gelisol Le changement climatique et la sante]. PMID- 27255636 TI - [Retroaction efficace durant la residence en medecine familiale]. PMID- 27255637 TI - Linoelaidic acid enhances adipogenic differentiation in adipose tissue-derived stromal cells through suppression of Wnt/beta-catenin signaling pathway in vitro. AB - Obesity has become a major health problem which is related with high-trans fatty acids diet. Adipogenic differentiation of adipose tissue-derived stromal cells (ADSCs) plays an important role in the development of adipose tissue. In order to determine the effect of trans fatty acids on adipogenic differentiation in ADSCs, cells were treated with linoelaidic acid, as well as linoleic acid and linolenic acid. We found that linoelaidic acid significantly increased the lipid droplet formation and triglyceride content compared with linoleic acid and linolenic acid. Linoelaidic acid also down-regulated the levels of beta-catenin in cells and inhibited the accumulation of beta-catenin in cell nuclei. Lithium chloride, an activator of Wnt/beta-catenin pathway, antagonized the enhancement of linoelaidic acid on adipogenesis and up-regulated the levels of beta-catenin in ADSCs. These results indicated that linoelaidic acid could enhance the adipogenic differentiation in ADSCs in vitro, which is partly due to the suppression of Wnt/beta-catenin pathway. PMID- 27255638 TI - Reducing dietary intake of linoleic acid of mouse dams during lactation increases offspring brain n-3 LCPUFA content. AB - Omega (n-)3 and n-6 long chain polyunsaturated fatty acids (LCPUFA) accumulation in the infant brain after birth is strongly driven by dietary supply of n-3 and n 6 LCPUFAs and their C18 precursors through breast milk or infant formula. n-3 LCPUFA accretion is associated with positive effects on neurodevelopmental outcome whereas high n-6 LCPUFA accumulation is considered disadvantageous. Maternal diet is crucial for breast milk fatty acid composition. Unfortunately, global increases in linoleic acid (C18:2n-6; LA) intake have dramatically increased n-6 LCPUFA and reduced n-3 LCPUFA availability for breastfed infants. We investigated the effects of reducing maternal dietary LA, or increasing n-3 LCPUFA, during lactation on milk and offspring brain fatty acids in mice. Offspring brain n-3 LCPUFA was higher following both interventions, although effects were mediated by different mechanisms. Because of competitive interactions between n-3 and n-6 fatty acids, lowering maternal LA intake may support neurodevelopment in breastfed infants. PMID- 27255639 TI - Astrocyte arachidonate and palmitate uptake and metabolism is differentially modulated by dibutyryl-cAMP treatment. AB - Astrocytes play a vital role in brain lipid metabolism; however the impact of the phenotypic shift in astrocytes to a reactive state on arachidonic acid metabolism is unknown. Therefore, we determined the impact of dibutyryl-cAMP (dBcAMP) treatment on radiolabeled arachidonic acid ([1-(14)C]20:4n-6) and palmitic acid ([1-(14)C]16:0) uptake and metabolism in primary cultured murine cortical astrocytes. In dBcAMP treated astrocytes, total [1-(14)C]20:4n-6 uptake was increased 1.9-fold compared to control, while total [1-(14)C]16:0 uptake was unaffected. Gene expression of long-chain acyl-CoA synthetases (Acsl), acyl-CoA hydrolase (Acot7), fatty acid binding protein(s) (Fabp) and alpha-synuclein (Snca) were determined using qRT-PCR. dBcAMP treatment increased expression of Acsl3 (4.8-fold) and Acsl4 (1.3-fold), which preferentially use [1-(14)C]20:4n-6 and are highly expressed in astrocytes, consistent with the increase in [1 (14)C]20:4n-6 uptake. However, expression of Fabp5 and Fabp7 were significantly reduced by 25% and 45%, respectively. Acot7 (20%) was also reduced, suggesting dBcAMP treatment favors acyl-CoA formation. dBcAMP treatment enhanced [1 (14)C]20:4n-6 (2.2-fold) and [1-(14)C]16:0 (1.6-fold) esterification into total phospholipids, but the greater esterification of [1-(14)C]20:4n-6 is consistent with the observed uptake through increased Acsl, but not Fabp expression. Although total [1-(14)C]16:0 uptake was not affected, there was a dramatic decrease in [1-(14)C]16:0 in the free fatty acid pool as esterification into the phospholipid pool was increased, which is consistent with the increase in Acsl3 and Acsl4 expression. In summary, our data demonstrates that dBcAMP treatment increases [1-(14)C]20:4n-6 uptake in astrocytes and this increase appears to be due to increased expression of Acsl3 and Acsl4 coupled with a reduction in Acot7 expression. PMID- 27255640 TI - The role of endogenous opioid peptides in the antinociceptive effect of 15 deoxy(Delta12,14)-prostaglandin J2 in the temporomandibular joint. AB - We have previously demonstrated that peripheral administration of 15d-PGJ2 in the Temporomandibular joint (TMJ) of rats can prevent nociceptor sensitization, mediated by peroxisome proliferator activated receptor-gamma (PPAR-gamma), and kappa- and delta- opioid receptors. However, the mechanism that underlies the signaling of PPAR-gamma (upon activation by 15d-PGJ2) to induce antinociception, and how the opioid receptors are activated via 15d-PGJ2 are not fully understood. This study demonstrates that peripheral antinociceptive effect of 15d-PGJ2 is mediated by PPAR-gamma expressed in the inflammatory cells of TMJ tissues. Once activated by 15d-PGJ2, PPAR-gamma induces the release of beta-endorphin and dynorphin, which activates kappa- and delta-opioid receptors in primary sensory neurons to induce the antinociceptive effect. PMID- 27255641 TI - Low immune cell ARA and high plasma 12-HETE and 17-HDHA in iron-deficient South African school children with allergy. AB - Allergy has been associated with altered fatty acid and inflammatory status. In this cross-sectional study of 321 rural iron deficient (ID) South African children (aged 6-11 years), a subsample (n=111) of children with parent-reported allergy data were divided into an allergic (n=30) and non-allergic (n=81) group and compared. PBMC arachidonic acid (ARA; P=0.010) and the PBMC ARA to dihomo gamma-linolenic acid (DGLA) ratio (P=0.035) were lower in the allergic children. Plasma 12-hydroxyeicosatetraenoic acid and 17-hydroxydocosahexaenoic acid (17 HDHA) were higher (P=0.040 and 0.020, respectively) in the allergic group. Thus, a fatty acid composition and lipid mediator levels indicative of increased release of ARA from PBMC membranes, increased inflammation as well as the resolving thereof, were associated with parent-reported allergy symptoms. This study used baseline data of an intervention study which was registered at clinicaltrials.gov as NCT01092377. PMID- 27255642 TI - People with schizophrenia and depression have a low omega-3 index. AB - Cardiovascular disease (CVD) is higher in people with mental illness and is associated with a 30 year higher mortality rate in this population. Erythrocyte docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (omega-3 index)<=4% is a marker for increased mortality risk from CVD while >8% is protective. Omega 3 polyunsaturated fatty acids are also important for brain function and may ameliorate symptoms of mental illness. We investigated the erythrocyte omega-3 index in people with mental illness. One hundred and thirty adults aged 18-65 years (32.6% male) with schizophrenia (n=14) and depression (n=116) provided blood samples and completed physiological assessments and questionnaires. Both populations had risk factors for metabolic syndrome and CVD. The average omega-3 index was 3.95% (SD=1.06), compared to an estimated 5% in the Australian population. These data indicate an unfavourable omega-3 profile in people with mental illness that could contribute to higher CVD risk. PMID- 27255643 TI - MicroRNA-125b: association with disease activity and the treatment response of patients with early rheumatoid arthritis. AB - BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression by targeting mRNA. It was proved that some miRNAs are significantly deregulated in rheumatoid arthritis (RA). MicroRNA-125b negatively regulates expression of TNF alpha, which plays a crucial role in RA pathogenesis. The aim of this study was to determine the treatment outcome of patients with early RA based on the expression of circulating and cellular miR-125b. METHODS: Total RNA was isolated from the plasma and peripheral blood mononuclear cells (PBMCs) of 58 patients with early RA before and three months after treatment initiation and of 54 age- and sex-matched healthy controls (HC). The expression of miR-125b was measured by TaqMan quantitative PCR. The treatment responders were defined as patients achieving remission or low disease activity (28-joint count disease activity score (DAS28) <3.2). Receiver operating characteristic (ROC) curve and stepwise backward multivariable logistic regression analyses of miR-125b expression were used to predict the disease outcome at three and six months after initiation of treatment. RESULTS: The expression of miR-125b in the PBMCs and plasma of treatment-naive early RA patients was significantly lower than that of HC and increased significantly after three months of treatment, particularly in responders. However, only the cellular expression of miR-125b was inversely correlated with disease activity. MiR-125b expression in PBMCs was higher in responders than in non-responders after three months (p = 0.042). Using ROC analysis, the cellular expression of miR-125b, but not the disease activity at baseline, predicted the treatment response after three months of therapy (area under the curve 0.652 (95 % CI 0.510 to 0.793); p = 0.048). CONCLUSION: The expression of miR-125b in PBMCs of treatment-naive patients may present a novel biomarker for monitoring the treatment outcome during the early phase of RA. PMID- 27255644 TI - Hyponatremia at discharge as a predictor of 12-month clinical outcomes in hospital survivors after acute myocardial infarction. AB - Hyponatremia in the early phase of acute myocardial infarction (AMI) is a well known predictor of poor prognosis. However, little is known about the clinical implication of sodium levels at discharge in hospital survivors after AMI. The study included 1290 consecutive patients (64 +/- 12 years; 877 men) who survived the index hospitalization after AMI. We determined the 12-month mortality rates of these patients. Patients who died during the 12-month follow-up had lower sodium levels at discharge than those who had survived (137 +/- 6 vs. 139 +/- 4 mmol/L; P < 0.014). Hyponatremia at discharge, defined as a serum sodium level <=135 mmol/L, was present in 210 patients (16.3 %). In the Cox-proportional hazard model, hyponatremia at discharge (hazard ratio, 2.264; 95 % confidence interval, 1.119-4.579; P = 0.023) was an independent predictor of 12-month mortality. Moreover, hyponatremia at discharge had an incremental prognostic value over conventional risk factors (chi 2 = 7, P = 0.007), and conventional risk factors and log N-terminal Pro-B-type natriuretic peptide combined (chi 2 = 5, P = 0.021). In the subgroup analysis, the 12-month mortality of patients with hyponatremia at discharge was significantly higher than in those without, irrespective of age, Killip class, left ventricular ejection fraction, percutaneous coronary intervention at index hospitalization, and prescription of diuretics at discharge. Hyponatremia at discharge is an independent predictor of 12-month mortality in hospital survivors after AMI. PMID- 27255645 TI - iMAPTM imaging of tumorous lesions surrounding the coronary arteries in a patient with an elevated serum level of immunoglobulin G4. AB - A 76-year-old woman with multiple coronary risk factors was admitted to our hospital because of episodes of new-onset chest pain that had begun 3 days previously. She underwent percutaneous coronary intervention (PCI) for severe stenoses in the two high lateral (HL) branches. Intravascular ultrasound (IVUS) revealed massive stenotic lesions in the HL branches and tumorous nonstenotic lesions in the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LCx). iMAPTM, optical coherence tomography (OCT), and coronary computed tomography angiography (CCTA) were performed. iMAP depicted fibrosis in the vessel (green areas) and nonfibrotic tissue change suggestive of inflammation outside the vessel (yellow/red areas). OCT revealed high-intensity homogenous intimal hyperplasia with superficial calcification, and CCTA showed massive periarterial soft lesions in the HL, LAD, and LCx. The serum IgG4 level was high at 252-427 mg/dL (8 measurements) (reference range, 4.8-105.0 mg/dL). We suspected IgG4-related coronary periarteritis on the basis of the comprehensive diagnostic criteria as a possible diagnosis. The clinical course was good after initial and subsequent PCIs for both the HL stenoses and the progressing LCx stenosis, and there was no recurrence of angina pectoris thereafter. Steroids were not administered because the massive lesions did not enlarge during the 16 months of follow-up. iMAP was able to evaluate the tissue characteristics of tumorous lesions in the stenosed HL branches and the nonstenotic LAD and LCx in a patient with an elevated level of IgG4. PMID- 27255647 TI - Effect of Gaussian curvature modulus on the shape of deformed hollow spherical objects. AB - A popular description of soft membranes uses the surface curvature energy introduced by Helfrich, which includes a spontaneous curvature parameter. In this paper we show how the Helfrich formula can also be of interest for a wider class of spherical elastic surfaces, namely with shear elasticity, and likely to model other deformable hollow objects. The key point is that when a stress-free state with spherical symmetry exists before subsequent deformation, its straightforwardly determined curvature ("geometrical spontaneous curvature") differs most of the time from the Helfrich spontaneous curvature parameter that should be considered in order to have the model being correctly used. Using the geometrical curvature in a set of independent parameters unveils the role of the Gaussian curvature modulus, which appears to play on the shape of an elastic surface even though this latter is closed, contrary to what happens for surfaces without spontaneous curvature. In appendices, clues are given to apply this alternative and convenient formulation of the elastic surface model to the particular case of thin spherical shells of isotropic material (TSSIMs). PMID- 27255646 TI - Latent pathogenicity of the G38S polymorphism of KCNE1 K+ channel modulator. AB - KCNE1 encodes a modulator of KCNQ1 and KCNH2 channels. Although KCNE1(G38S), a single-nucleotide polymorphism (SNP) causing a G38S substitution in KCNE1, is found frequently, whether and how this SNP causes long QT syndrome (LQTS) remains unclear. We evaluated rate-dependent repolarization dynamics using Holter electrocardiogram (ECG) to assess the pathogenicity of KCNE1(G38S). Forty-five patients exhibiting long QT intervals, as assessed by their baseline ECGs, and 16 control subjects were enrolled. KCNE1(G38S) carriers were identified using genome sequencing. LQTS patients were classified into LQT1 or LQT2 using genetic analysis or epinephrine test. QT-RR relations were determined using 24-h Holter ECG recordings. Among the 15 patients (33.3 %) with KCNE1(G38S), four patients without any mutations or amino acid changes in other major cardiac ion channels were categorized as KCNE1(G38S) carriers. In the QT-RR regression lines, the QT RR slope was greater in the KCNE1(G38S) carriers and the LQT2 patients (0.215 +/- 0.021 and 0.207 +/- 0.032, respectively) than in the LQT1 patients (0.163 +/- 0.014, P < 0.05) and the control subjects (0.135 +/- 0.025, P < 0.001). The calculated QT intervals at an RR interval of 1200 ms were longer in the KCNE1(G38S) carriers and LQT1 and LQT2 patients than in the control subjects. Patients with KCNE1(G38S) had a rate-dependent repolarization abnormality similar to patients with LQT2 and, therefore, may have a potential risk to develop lethal arrhythmias. PMID- 27255649 TI - Paediatric life support courses for health centres in low and middle income countries. PMID- 27255648 TI - Economic cost analysis of malaria case management at the household level during the malaria elimination phase in The People's Republic of China. AB - BACKGROUND: In China, malaria has been posing a significant economic burden on households. To evaluate malaria economic burden in terms of both direct and indirect costs has its meaning in improving the effectiveness of malaria elimination program in China. METHODS: A number of study sites (eight counties in five provinces) were selected from the malaria endemic area in China, representing the different levels of malaria incidence, risk classification, economic development. A number of households with malaria cases (n = 923) were surveyed during the May to December in 2012 to collect information on malaria economic burden. Descriptive statistics were used to characterize the basic profiles of selected malaria cases in terms of their gender, age group, occupation and malaria type. The malaria economic costs were evaluated by direct and indirect costs. Comparisons were carried out by using the chi-square test (or Z-test) and the Mann-Whitney U test among malaria cases with reference to local/imported malaria patients, hospitalized/out patients, and treatment hospitals. RESULTS: The average cost of malaria per case was 1 691.23 CNY (direct cost was 735.41 CNY and indirect cost was 955.82 CNY), which accounted for 11.1 % of a household's total income. The average costs per case for local and imported malaria were 1 087.58 CNY and 4271.93 CNY, respectively. The average cost of a malaria patient being diagnosed and treated in a hospital at the county level or above (3 975.43 CNY) was 4.23 times higher than that of malaria patient being diagnosed and treated at a village or township hospital (938.80 CNY). CONCLUSION: This study found that malaria has been posing a significant economic burden on households in terms of direct and indirect costs. There is a need to improve the effectiveness of interventions in order to reduce the impact costs of malaria, especially of imported infections, in order to eliminate the disease in China. PMID- 27255650 TI - Disparities in time trends of cervical cancer mortality rates in Brazil. AB - PURPOSE: This study aimed to correct and describe cervical cancer mortality rates and trends by regions and age-groups in Brazil. It may help planning and implementing policies for cervical cancer control. METHODS: Data from 2003 to 2012 were accessed through the centralized national mortality database. Correction of the age-specific mortality rates was done by proportional redistribution of ill-defined causes of death and deaths coded as 'uterine, part unspecified'. Annual percentage change (APC) was obtained by trend analysis (Joinpoint regression). RESULTS: In the 10-year period, cancer and ill-defined causes corresponded, respectively, to 18.9 and 10.8 % of all deaths (except injuries). The proportion of ill-defined causes was reduced by more than a half in the period. The age-standardized cervical cancer mortality rate was 7.2 per 100,000 women-years after correction. The total increase in rates after corrections was 50.5 %. A significant decreasing trend in rates was observed at the national level (APC = -0.17, p < 0.001). North was the only region that did not show a decreasing significant trend (APC + 0.07, p = 0.28). Decreasing trends were restricted to age-groups over 40 years. CONCLUSIONS: A consistent decreasing trend of cervical cancer mortality rates in Brazil from 2003 to 2012 was observed, although this was not consistent in all regions and restricted to older age-groups. Quality of data needs to be improved. Cancer control policies may consider the differences in access to care and the characteristics of regions to improve their efficiency. PMID- 27255652 TI - FLT-PET/CT diagnosis of primary and metastatic nodal lesions of gastric cancer: comparison with FDG-PET/CT. AB - PURPOSE: To examine the diagnostic performance of (18)F-fluorothymidine (FLT) PET/CT of primary and metastatic nodal lesions of gastric cancer by comparing with (18)F-fluorodeoxyglucose (FDG)-PET/CT. METHODS: The enrolled study population comprised 17 patients with 17 newly diagnosed gastric cancers who underwent surgery of the primary lesion and regional nodes after both FDG- and FLT-PET/CT scans. Visual detectability of the primary gastric lesions was correlated with pathological factors using the Fisher exact or Mann-Whitney U test. The sensitivity, specificity, and accuracy in detecting nodal lesions were compared between both PET/CT scans using the McNemar exact or chi (2) test. RESULTS: Fourteen of 17 (82.4%) primary cancers were visualized by both FDG- and FLT-PET/CT scans. Although FDG or FLT visibility was not significantly associated with tumor size (p = 0.16) or histological type (p = 1.00), the 3 nonvisible lesions were pathologically early (T1) cancers. The sensitivity, specificity, and accuracy for detecting nodal metastasis were 44.8% (13/29), 98.7% (164/166), and 90.8% (177/195) for FDG-PET/CT, and 31.0% (9/29), 100% (166/166), and 89.7% (175/195) for FLT-PET/CT, respectively. No significant difference was found between the two scans in sensitivity (p = 0.13), specificity (p = 0.48), or accuracy (p = 1.00). CONCLUSION: FLT-PET/CT may have the same diagnostic value as FDG-PET/CT for detection of primary and nodal lesions of gastric cancer. PMID- 27255653 TI - Exposure Variation and Endocrine Disruption of the Male Reproductive System. AB - Exposure to endocrine disruptors varies geographically and temporally. Environmental levels of persistent organic pollutants have decreased after international regulation, whereas potential exposure to thousands of new chemicals has increased. The adverse effects of endocrine disruptors depend on susceptibility and timing of the exposure. Fetal and childhood exposures are often most harmful because of organizational and programming effects. In this review, we use the exposure to persistent organic pollutants such as polybrominated diphenyl ethers, dioxins and dioxin-like polychlorinated biphenyls and differences in the incidence of reproductive disorders between Denmark and Finland as an example to highlight how exposure variation and variation in genetic susceptibility may influence the strength of the association between the exposure to endocrine disruptors and adverse effects. Understanding the causes and implications of interindividual differences in susceptibility to endocrine disruptors is crucial for the protection of normal development. PMID- 27255651 TI - Insights into the role of sulfated glycans in cancer cell adhesion and migration through use of branched peptide probe. AB - The tetra-branched peptide NT4 selectively binds to different human cancer cells and tissues. NT4 specifically binds to sulfated glycosaminoglycans on cancer cell membranes. Since sulfated glycosaminoglycans are involved in cancer cell interaction with the extracellular matrix, we evaluated the effect of NT4 on cancer cell adhesion and migration. We demonstrated here that the branched peptide NT4 binds sulfated glycosaminoglycans with high affinity and with preferential binding to heparan sulfate. NT4 inhibits cancer cell adhesion and migration on different proteins, without modifying cancer cell morphology or their ability to produce protrusions, but dramatically affecting the directionality and polarity of cell movement. Results obtained by taking advantage of the selective targeting of glycosaminoglycans chains by NT4, provide insights into the role of heparan sulfate proteoglycans in cancer cell adhesion and migration and suggest a determinant role of sulfated glycosaminoglycans in the control of cancer cell directional migration. PMID- 27255654 TI - Evaluation of degenerative disease of the lumbar spine: MR/MR myelography versus conventional myelography/post-myelography CT. AB - BACKGROUND: To compare the use of magnetic resonance (MR)/MR myelography (MRM) with conventional myelography/post-myelography CT (convM) for detailed surgery planning in degenerative lumbar disease. METHODS: Twenty-six patients with suspected complex lumbar degenerative disease underwent MRM in addition to convM as preoperative workup. Surgery was planned based on convM-as usual at our department. Post hoc, surgical planning was repeated planned again-now based on MRM. Furthermore, the MRM-based planning was performed by six independent neurosurgeons (three groups) of different degrees of specialisation. RESULTS: In only 31 % of the patients, post hoc MRM-based planning resulted in the same surgical decision as originally performed, whereas in 69 % (n = 18) a different procedure was indicated. In patients with non-concurring convM- and MRM-based surgical plans, a less extended procedure was the result of MRM in six patients (23 %), a more extended one in five (19 %), and a related to side/level of decompression or nucleotomy different plan in six patients (23 %). In one patient (4 %), the MRM-based planning would have led to a completely different surgery compared to convM. Overall interobserver agreement on the MRM-based planning was substantial. CONCLUSIONS: Detailed planning of operative procedures for complex lumbar degenerative disease is highly dependent on the image modality used. PMID- 27255655 TI - Endoscope-assisted, minimally invasive evacuation of sub-acute/chronic epidural hematoma: Novelty or paradox of Theseus? AB - BACKGROUND: Sub-acute/chronic epidural hematoma (EDH) may present with nagging symptoms of headache, nausea, vomiting, lethargy, etc. We attempted to offer a minimally invasive, single burr hole, endoscope-assisted evacuation of EDHs instead of a conventional craniotomy. METHODS: Seven patients with sub acute/chronic EDH (six supratentorial and one infratentorial) presented to us 3 to 7 days after low-velocity road traffic accidents with complaints of headache and lethargy. The EDH volumes measured between 20 to 50 ml, and the patients were operated on using a single burr hole made through a small incision. We used 0-, 30- and 70-degree, angulated, rigid, high-definition endoscopes to identify and evacuate the organized clots in the extradural space. Flexible catheters were used for suction and irrigation. After achieving hemostasis, the dura was hitched back to the burr hole site. The wound was closed over a negative suction drain. RESULTS: All patients had prompt recovery from symptoms. Postoperative CT scans showed complete or near complete evacuation of the hematomas. The hospital stay and analgesic requirements were minimal. There was no infective complication or conversion to conventional open surgery. The average time for surgery was 77.8 min, and average blood loss was 328.5 ml. CONCLUSION: Endoscope-assisted evacuation of sub-acute/chronic EDH is a novel concept, which offers quick relief from symptoms in a minimally invasive fashion and a cosmetically acceptable way. None of the standard principles of surgery are hampered. It avoids extensive dissection of the temporalis or sub-occipital muscles. However, achieving hemostasis can be difficult. Further study and better equipment will validate the procedure. PMID- 27255656 TI - Detection of carotid artery stenosis using histological specimens: a comparison of CT angiography, magnetic resonance angiography, digital subtraction angiography and Doppler ultrasonography. AB - BACKGROUND: Carotid endarterectomy (CEA) is accepted as a primary modality to treat carotid stenosis. The accuracy of measuring carotid stenosis is important for indication of the CEA procedure. Different diagnostic tools have been developed and used in the past 2 decades for the diagnosis of carotid stenosis. Only a few studies, however, have focused on the comparison of different diagnostic tools to histological findings of carotid plaque. METHOD: Patients with internal carotid artery (ICA) stenosis were investigated primarily by computed tomography angiography (CTA). Digital subtraction angiography (DSA), Doppler ultrasonography (DUS) and magnetic resonance angiography (MRA) were performed as well. Atherosclerotic plaque specimens were transversally cut into smaller segments and histologically processed. The slides were scanned and specimens showing maximal stenosis were determined; the minimal diameter and the diameter of the whole plaque were measured. High quality histological specimen and histological measurement was considered to be the prerequisite for inclusion into the analysis. The preoperative findings were compared with histological measurement. CTA and histological measurements were obtained from 152 patients. DSA measurements were available in 138 of these cases, MRA in 107 and DUS in 88. A comparison between preoperative and histological findings was performed. In addition, correlation coefficients were computed and tested. RESULTS: A significant correlation was found for each of the diagnostic procedures. The strongest correlation coefficient and the best allocation of stenosis into clinical significant groups (<50 %, 50-69 %, >=70 %) was observed for CTA. Mean differences in the whole cohort between preoperative and histological measurements were as follows: CTA underestimated histological measurement by 2.4 % (based on European Carotid Surgery Trial [ECST] methodology) and 11.9 % (based on North American Symptomatic Carotid Endarterectomy Trial [NASCET] methodology). DSA underestimated the histological measurement by 7 % (ECST) and 12.2 % (NASCET). MRA overestimated the histological measurement by 2.6 % (ECST) and underestimated by 0.6 % (NASCET). DUS overestimated the stenosis by 1.8 %. CONCLUSIONS: CTA yields the best accuracy in detection of carotid stenosis, provided that all axial slices of the stenosis are checked and carefully analysed. DSA underestimates moderate and mild ICA stenosis, whereas DUS overestimates high-grade ICA stenosis. For MRA, a relatively low correlation coefficient was observed with histological findings. We conclude that CTA-ecst technique is the most reliable technique for carotid stenosis measurement. PMID- 27255657 TI - Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer. AB - Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI >=3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4-67.3 %] vs. 69.2 % [95 % CI 64.2-73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67-0.93, p = 0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes. PMID- 27255658 TI - The Likely Sites of Nodal Metastasis Differs According to the Tumor Extent in Distal Bile Duct Cancer. AB - BACKGROUND: In the revised Japanese and Worldwide TNM classification of distal bile duct cancer, the lymph node status is defined as N0 or N1 without reference to the tumor location or extent, according to the presence/absence of metastasis to the regional lymph nodes. METHODS: Data of 94 patients with distal bile duct cancer who had undergone pancreaticoduodenectomy were reviewed retrospectively. In formalin-fixed specimens, we measured the longitudinal lengths from the papilla to the lower and upper margins of the tumor, in order to investigate the correlation of the tumor extent with the likely sites of nodal metastasis. RESULTS: The frequencies of metastasis to the posterior pancreaticoduodenal nodes (7.1 %) and superior mesenteric artery nodes (0.0 %) were significantly lower in the cases in which the length from the papilla to the lower margin of the tumor was >=30 mm. The frequencies of nodal metastasis to the common hepatic artery nodes (0.0 %) and hepatoduodenal ligament nodes (6.7 %) were significantly lower in the cases in which the length from the papilla to the upper margin was <40 mm. CONCLUSION: The likely sites of nodal metastasis differ according to the extent of the tumor in cases of bile duct cancer. PMID- 27255659 TI - Targeted lipid-polyaniline hybrid nanoparticles for photoacoustic imaging guided photothermal therapy of cancer. AB - Designing a targeted and versatile photothermal agent for the integration of precise diagnosis and effective photothermal treatment of tumors is desirable but remains a great challenge. In this study, folic acid ligand conjugated lipid coated polyaniline hybrid nanoparticles (FA-Lipid-PANI NPs) were successfully fabricated by a distinctive technology. The obtained hybrid FA-Lipid-PANI NPs with small size exhibited not only significant photoacoustic (PA) imaging signals, but also a remarkable photothermal effect for tumor treatment. With PA imaging and photothermal therapy (PTT), the tumor could be accurately positioned and thoroughly eradicated in vivo after intravenous injection of FA-Lipid-PANI NPs. These multifunctional nanoparticles could play an important role in simultaneously facilitating imaging and PTT to achieve better therapeutic efficacy. PMID- 27255660 TI - Bone Mineral Density Is Negatively Associated With Arterial Stiffness in Men With Hypertension. AB - Hypertension (HTN) and osteoporosis are associated with the development and progress of atherosclerosis. However, little research has been conducted to examine the relationship between arterial stiffness and bone mineral density (BMD) in men with HTN. This cross-sectional study recruited 355 men with HTN and 353 control patients without HTN. Brachial-ankle pulse wave velocity (baPWV) and BMD measurements were performed. BMD was decreased and baPWV was elevated in patients with HTN compared with control patients (femoral neck [FN] BMD in the HTN and control groups were 0.662+/-0.195 g/cm2 and 0.713+/-0.204 g/cm2 , respectively [P=.001], and baPWV in the HTN and control groups were 1403.3+/ 156.8 cm/s and 1354.8+/-136.0 cm/s, respectively [P<.001]). Multiple linear regression analysis demonstrated that FN BMD was negatively associated with increased baPWV in HTN. Reduced FN BMD may be an independent factor for baPWV in patients with HTN. PMID- 27255661 TI - Clinical Prognostic Factors and Survival Outcome Of Chronic Myelomonocytic Leukemia: Reviewing 3,686 Patients. PMID- 27255662 TI - Impact of Body Mass Index on the Prognosis of Japanese Patients With Non-Valvular Atrial Fibrillation. AB - Obesity is a risk factor for atrial fibrillation (AF); however, obesity is associated with lower mortality in patients with established AF, a phenomenon known as the obesity paradox. Previous studies reported inconsistent results regarding effects of body weight on risk of cardiogenic embolism in patients with AF. To determine relation between body mass index (BMI) and prognosis among Japanese patients with nonvalvular AF (NVAF), a post hoc analysis was conducted using observational data in the J-RHYTHM Registry. Subjects were categorized as underweight (BMI <18.5), normal (18.5 to 24.9), overweight (25.0 to 29.9), or obese (>=30 kg/m(2)). End points included thromboembolism, major hemorrhaging, all-cause mortality, and cardiovascular mortality. Of the 7,406 patients with NVAF, 6,379 patients (70 +/- 10 years old; BMI, 23.6 +/- 3.9 kg/m(2)) having baseline BMI data constituted the study group. During the 2-year follow-up period, 111 patients had thromboembolism, 124 experienced major hemorrhage, and 159 died. Multivariate analysis with the Cox proportional hazards model showed that none of the BMI categories were independent predictors of thromboembolism. However, being underweight was an independent predictor of all-cause mortality (hazard ratio [HR] 2.45; 95% confidence interval [CI] 1.62 to 3.69; p <0.001) and cardiovascular mortality (HR 3.00, 95% CI 1.52 to 5.91, p = 0.001) when normal weight was used as the reference. Additionally, being overweight was a predictor of lower all-cause mortality (HR 0.60, 95% CI 0.37 to 0.95, p = 0.029). In conclusion, being underweight is associated with higher risks of all-cause and cardiovascular mortality compared with having a normal weight. Being overweight or obese is not associated with increased mortality among Japanese patients with NVAF. PMID- 27255663 TI - IGF1R as a Key Target in High Risk, Metastatic Medulloblastoma. AB - Risk or presence of metastasis in medulloblastoma causes substantial treatment related morbidity and overall mortality. Through the comparison of cytokines and growth factors in the cerebrospinal fluid (CSF) of metastatic medulloblastoma patients with factors also in conditioned media of metastatic MYC amplified medulloblastoma or leptomeningeal cells, we were led to explore the bioactivity of IGF1 in medulloblastoma by elevated CSF levels of IGF1, IGF-sequestering IGFBP3, IGFBP3-cleaving proteases (MMP and tPA), and protease modulators (TIMP1 and PAI-1). IGF1 led not only to receptor phosphorylation but also accelerated migration/adhesion in MYC amplified medulloblastoma cells in the context of appropriate matrix or meningothelial cells. Clinical correlation suggests a peri /sub-meningothelial source of IGF-liberating proteases that could facilitate leptomeningeal metastasis. In parallel, studies of key factors responsible for cell autonomous growth in MYC amplified medulloblastoma prioritized IGF1R inhibitors. Together, our studies identify IGF1R as a high value target for clinical trials in high risk medulloblastoma. PMID- 27255666 TI - Spatial and temporal variability in the otolith chemistry of the Brazilian snapper Lutjanus alexandrei from estuarine and coastal environments. AB - Otolith chemistry of juvenile and adult individuals of the Brazilian snapper Lutjanus alexandrei was measured to assess the utility of natural markers for investigating individual movements. Individuals were collected over a 3-year period (2010-2012) along the north-eastern coast of Brazil from both estuarine (juvenile to sub-adult stages) and coastal (sub-adult to adult stages) areas. Six elements ((7) Li, (24) Mg, (55) Mn, (59) Co, (88) Sr and (137) Ba) were measured in sectioned otoliths of L. alexandrei using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Edge composition analysis indicated that element:Ca ratios in the otoliths of juvenile and sub-adult L. alexandrei from estuaries were not significantly different among the three consecutive years (2010, 2011 and 2012), suggesting that physicochemical conditions within the nursery area investigated were temporally stable. Similarly, apart from two elements (Ba and Co), element:Ca ratios for larger L. alexandrei inhabiting coastal waters were also similar. In contrast, otolith chemistry of similar sized L. alexandrei from estuarine and coastal areas was significantly different (based on recently accreted material). Otolith Mn:Ca and Ba:Ca were both significantly higher for L. alexandrei collected in estuaries compared to fish from adjacent coastal reefs, while the opposite trend was observed for Sr:Ca. Given the pronounced differences in otolith chemistry between estuarine and coastal areas, element:Ca transects were constructed from the core to margin of the otoliths for adults (age 7+ years) collected on reefs to determine the timing of movement (ontogenetic migration) from estuarine to coastal areas. Based on observed patterns of decline for both Mn:Ca and Ba:Ca, it appears that L. alexandrei begin the move to more coastal habitats (i.e. lower element:Ca ratios) after age 2 years. The patterns observed for this species highlight the importance of conserving connectivity between coastal habitats to maintain sustainable fish stocks exploited by artisanal fisheries. PMID- 27255665 TI - The spectrum of ectopic thymomas. AB - Thymomas are rare tumors that usually manifest in the anterosuperior mediastinum. Occasionally, thymomas may also originate from ectopically dispersed thymic tissue and can arise in locations such as the neck, lung, or pleura or other locations in the thoracic cavity. The occurrence of thymomas in these ectopic locations can cause substantial diagnostic difficulty as the entity is almost never included in the differential diagnosis and its biphasic morphology can cause further complications during the diagnostic process. In this review, we summarize the clinical and pathological spectrum of ectopic thymomas and discuss the histogenesis, treatment, and prognosis of these extraordinary tumors. PMID- 27255664 TI - Mechanisms, pools, and sites of spontaneous vesicle release at synapses of rod and cone photoreceptors. AB - Photoreceptors have depolarized resting potentials that stimulate calcium dependent release continuously from a large vesicle pool but neurons can also release vesicles without stimulation. We characterized the Ca(2+) dependence, vesicle pools, and release sites involved in spontaneous release at photoreceptor ribbon synapses. In whole-cell recordings from light-adapted horizontal cells (HCs) of tiger salamander retina, we detected miniature excitatory post-synaptic currents (mEPSCs) when no stimulation was applied to promote exocytosis. Blocking Ca(2+) influx by lowering extracellular Ca(2+) , by application of Cd(2+) and other agents reduced the frequency of mEPSCs but did not eliminate them, indicating that mEPSCs can occur independently of Ca(2+) . We also measured release presynaptically from rods and cones by examining quantal glutamate transporter anion currents. Presynaptic quantal event frequency was reduced by Cd(2+) or by increased intracellular Ca(2+) buffering in rods, but not in cones, that were voltage clamped at -70 mV. By inhibiting the vesicle cycle with bafilomycin, we found the frequency of mEPSCs declined more rapidly than the amplitude of evoked excitatory post-synaptic currents (EPSCs) suggesting a possible separation between vesicle pools in evoked and spontaneous exocytosis. We mapped sites of Ca(2+) -independent release using total internal reflectance fluorescence (TIRF) microscopy to visualize fusion of individual vesicles loaded with dextran-conjugated pHrodo. Spontaneous release in rods occurred more frequently at non-ribbon sites than evoked release events. The function of Ca(2+) -independent spontaneous release at continuously active photoreceptor synapses remains unclear, but the low frequency of spontaneous quanta limits their impact on noise. PMID- 27255667 TI - The travesty of expensive insulin. PMID- 27255668 TI - Patients are being let down by lack of electronic health records, finds review. PMID- 27255671 TI - Proton pump inhibitor prescribing patterns in the UK: a primary care database study. AB - PURPOSE: To determine the prevalence and pattern of proton pump inhibitor (PPI) prescription and the practices employed to reduce PPI use in the UK general population. METHODS: The UK's Clinical Practice Research Database was used to identify individuals who were issued with >=1 PPI prescription during the period 1990-2014. Point and period prevalence of PPI use were estimated annually. Additionally, new users of PPI therapy who had 5 years of follow-up data were included in a cohort analysis to describe patterns of cessation and duration of PPI use. RESULTS: Both the period and point prevalence of PPI use increased between 1990 and 2014 (period prevalence increased from 0.2 to 15.0% and point from 0.03 to 7.7%). A total of 596 334 new users of PPI therapy in the cohort study received 8 784 272 prescriptions. Of these, 26.7% used PPI therapy long term (>=1 year continuously), while 3.9% remained on PPI therapy for 5 years. Clear attempts to step down dose were identified in 39.9% of long-term users, while this was 47% in patients whose initial indication did not mandate long-term use. CONCLUSION: A considerable increase in PPI use was observed in UK general practice. Of long-term PPI users, 60% did not have an attempt to discontinue or step down. Considerable opportunities may therefore exist to reduce the cost and side effects of PPI use through improving adherence to recommended withdrawal strategies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27255672 TI - Tandem dissolution of UO3 in amide-based acidic ionic liquid and in situ electrodeposition of UO2 with regeneration of the ionic liquid: a closed cycle. AB - A closed cycle is demonstrated for the tandem dissolution and electroreduction of UO3 to UO2 with regeneration of the acidic ionic liquid. The dissolution is achieved by use of the acidic ionic liquid [DMAH][NTf2] in [EMIM][NTf2] serving as the diluent. A sequential dissolution, electroreduction, and regeneration cycle is presented. PMID- 27255669 TI - Synthetic mixed-signal computation in living cells. AB - Living cells implement complex computations on the continuous environmental signals that they encounter. These computations involve both analogue- and digital-like processing of signals to give rise to complex developmental programs, context-dependent behaviours and homeostatic activities. In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately. Here we integrate analogue and digital computation to implement complex hybrid synthetic genetic programs in living cells. We present a framework for building comparator gene circuits to digitize analogue inputs based on different thresholds. We then demonstrate that comparators can be predictably composed together to build band-pass filters, ternary logic systems and multi-level analogue-to-digital converters. In addition, we interface these analogue-to-digital circuits with other digital gene circuits to enable concentration-dependent logic. We expect that this hybrid computational paradigm will enable new industrial, diagnostic and therapeutic applications with engineered cells. PMID- 27255673 TI - Relationship between [123 I]-FP-CIT SPECT and clinical progression in Parkinson's disease. AB - BACKGROUND: The demonstration of presynaptic dopaminergic deficiency on [123 I] FP-CIT SPECT imaging is a useful ancillary tool in the diagnosis of Parkinson's disease (PD). Whilst there is evidence of a cross-sectional relationship between the degree of dopaminergic deficiency and severity of bradykinesia and rigidity, longitudinal studies are rare. Moreover, the relationship between motor subtypes and their dopaminergic deficient state is not well characterized. AIM: Our primary aim was to assess the correlations between dopaminergic deficiency on baseline [123 I]-FP-CIT SPECT imaging with the progression of motor severity in patients classified by motor subtype, and the development of motor complications. Our secondary aim was to assess the correlation between UPDRS-III subscores and the time to onset of motor complications. METHODS: 42 PD patients with abnormal baseline [123 I]-FP-CIT SPECT scans and at least 3 years of clinical follow-up were classified by motor subtype: akinetic-rigid, tremor-dominant or mixed. UPDRS III scores at baseline and at 3-year follow-up, and time to onset of motor complications were recorded. RESULTS: [123 I]-FP-CIT uptake ratios were inversely correlated with UPDRS-III scores at 3 years only in akinetic-rigid patients (r= .51, P=.04). Time to onset of motor complications was inversely correlated with UPDRS-III subscores for bradykinesia and rigidity at baseline (r=-.52, P=.02) and at 3 years (r=-.54, P=.01). CONCLUSION: The degree of dopaminergic deficiency on baseline [123 I]-FP-CIT SPECT inversely correlates with motor severity at 3-year follow-up in akinetic-rigid patients only. Furthermore, UPDRS-III subscores for bradykinesia and rigidity at baseline show an inverse correlation with time to onset of motor complications across all PD subtypes. PMID- 27255675 TI - Carbon-Silicon Bond Formation in the Synthesis of Benzylic Silanes. AB - Sterically encumbered organosilanes can be difficult to synthesize with conventional, strongly basic reagents; the harsh reaction conditions are often low yielding and not suitable for many functional groups. As an alternative to the typical anionic strategies to construct silanes, the coupling of benzylic halides and arylhalosilanes with sonication has been identified as a high yielding and general strategy to access bulky and functionalized benzylic silanes. This new methodology provides a solution for the synthesis of families of bulky benzylic silanes for study in catalysis and other areas of chemical synthesis. PMID- 27255674 TI - Prescription of potentially inappropriate medication in Korean older adults based on 2012 Beers Criteria: a cross-sectional population based study. AB - BACKGROUND: A high number of elderly people with multiple comorbidities are exposed to the risk of polypharmacy and prescription of potentially inappropriate medication (PIM). The purpose of this study was to determine the prevalence and patterns of PIM prescription in Korean older adults according to the 2012 Beers Criteria. METHODS: A retrospective study was conducted using data from the Korean Health Insurance Review and Assessment (KHIRA) database of outpatient prescription claims collected from January 1, 2009 to December 31, 2011. A total of 523,811 elderly subjects aged 65 years and older were included in the study, and several covariates related to the prescription of PIMs were obtained from the KHIRA database. These covariates were analyzed using Student's t test and the chi square test; furthermore, multivariate logistic regression analysis was used to evaluate the risk factors associated with the prescription of PIMs. RESULTS: A total of 80.96 % subjects were prescribed at least one PIM independent of their diagnosis or condition according to the 2012 Beers Criteria. The most commonly prescribed medication class was first-generation antihistamines with anticholinergic properties (52.33 %). Pain medications (43.04 %) and benzodiazepines (42.53 %) were next in line. When considering subjects' diagnoses or conditions, subjects diagnosed with central nervous system conditions were most often prescribed PIMs. Female sex, severity of comorbidities, and polypharmacy were significant risk factors for PIM prescriptions. CONCLUSIONS: This study confirmed that PIM prescription is common among elderly Koreans. A clinical decision support system should be developed to decrease the prevalence of PIM prescriptions. PMID- 27255677 TI - Brevitalea aridisoli, B. deliciosa and Arenimicrobium luteum, three novel species of Acidobacteria subdivision 4 (class Blastocatellia) isolated from savanna soil and description of the novel family Pyrinomonadaceae. AB - Three novel strains of the phylum Acidobacteria (Ac_11_E3T, Ac_12_G8T and Ac_16_C4T) were isolated from Namibian semiarid savanna soils by a high throughput cultivation approach using low-nutrient growth media. 16S rRNA gene sequence analysis placed all three strains in the order Blastocatellales of the class Blastocatellia (Acidobacteria subdivision 4). However, 16S rRNA gene sequence similarities to their closest relative Pyrinomonas methylaliphatogenes K22T were <=90 %. Cells of strains Ac_11_E3T, Ac_12_G8T and Ac_16_C4T were Gram staining-negative and non-motile and divided by binary fission. Ac_11_E3T and Ac_16_C4T formed white colonies, while those of Ac_12_G8T were orange-yellowish. All three strains were aerobic chemoorganoheterotrophic mesophiles with a broad pH range for growth. All strains used a very limited spectrum of carbon and energy sources for growth, with a preference for complex proteinaceous substrates. The major respiratory quinone was MK-8. The major shared fatty acid was iso-C15 : 0. The DNA G+C contents of strains Ac_11_E3T, Ac_12_G8T and Ac_16_C4T were 55.9 mol%, 66.9 mol% and 54.7 mol%, respectively. Based on these characteristics, the two novel genera Brevitaleagen. nov. and Arenimicrobiumgen. nov. are proposed, harboring the novel species Brevitaleaaridisoli sp. nov. (Ac_11_E3T=DSM 27934T=LMG 28618T), Brevitalea deliciosa sp. nov. (Ac_16_C4T=DSM 29892T=LMG 28995T) and Arenimicrobium luteum sp. nov. (Ac_12_G8T=DSM 26556T=LMG 29166T), respectively. Since these novel genera are only distantly related to established families, we propose the novel family Pyrinomonadaceaefam. nov. that accommodates the proposed genera and the genus Pyrinomonas(Crowe et al., 2014). PMID- 27255676 TI - Direct repeat-mediated DNA deletion of the mating type MAT1-2 genes results in unidirectional mating type switching in Sclerotinia trifoliorum. AB - The necrotrophic fungal pathogen Sclerotinia trifoliorum exhibits ascospore dimorphism and unidirectional mating type switching - self-fertile strains derived from large ascospores produce both self-fertile (large-spores) and self sterile (small-spores) offsprings in a 4:4 ratio. The present study, comparing DNA sequences at MAT locus of both self-fertile and self-sterile strains, found four mating type genes (MAT1-1-1, MAT1-1-5, MAT1-2-1 and MAT1-2-4) in the self fertile strain. However, a 2891-bp region including the entire MAT1-2-1 and MAT1 2-4 genes had been completely deleted from the MAT locus in the self-sterile strain. Meanwhile, two copies of a 146-bp direct repeat motif flanking the deleted region were found in the self-fertile strain, but only one copy of this 146-bp motif (a part of the MAT1-1-1 gene) was present in the self-sterile strain. The two direct repeats were believed to be responsible for the deletion through homologous intra-molecular recombination in meiosis. Tetrad analyses showed that all small ascospore-derived strains lacked the missing DNA between the two direct repeats that was found in all large ascospore-derived strains. In addition, heterokaryons at the MAT locus were observed in field isolates as well as in laboratory derived isolates. PMID- 27255678 TI - Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03). AB - BACKGROUND: Experimental data demonstrated that concurrent anti-angiogenic treatment with sunitinib may improve the efficacy of radiation therapy (RT). Here we report the results of a phase I trial performed within the German Interdisciplinary Sarcoma Group (GISG-03) of combined sunitinib and RT for neoadjuvant treatment of locally advanced soft tissue sarcoma (STS). METHODS: The primary endpoint of the study was to explore the recommended dose of sunitinib combined with RT for subsequent trials. Treatment response, postoperative complications after tumor resection and toxicity according to CTCAE 4.0 were secondary endpoints. The study used a 3 + 3 design. Patients received either 25 mg (dose level 1) or 37.5 mg (dose level 2) sunitinib two weeks prior to and throughout RT (28 * 1.8 Gy). Surgery was scheduled 5-8 weeks after completion of neoadjuvant treatment. STUDY REGISTRATION: NCT01498835. RESULTS: Six patients were enrolled in dose level 1 and three patients in dose level 2. Median tumor size was 11 cm. Tumors were located in the retroperitoneum (4/9), lower leg (3/9) or trunk (2/9). At dose level 1, 1/6 patients developed dose limiting lymphopenia. At dose level 2, no patient developed dose limiting toxicity. Most frequent toxicities were hematological (8/9) and oral (5/9). Dose adjustments of sunitinib were necessary in 5/9 patients. All patients received full dose RT and underwent tumor resection (8/9 R0 and 1/9 R1). Local toxicity of RT did not exceed Grade 2. 2/9 patients had postoperative complications requiring re intervention. Treatment response according to RECIST was as follows: partial response 1/9, stable disease 7/9, and progressive disease 1/9. Pathological examination revealed >= 95 % tumor necrosis in 3/9 resected specimens. CONCLUSIONS: Combined sunitinib and RT was tolerable as neoadjuvant treatment for locally advanced STS patients regardless of tumor localization. The recommended sunitinib dose for subsequent trials is 37.5 mg. PMID- 27255679 TI - Utilizing dual energy CT to improve CT diagnosis of posterior fossa ischemia. AB - BACKGROUND AND PURPOSE: Evaluation of posterior fossa ischemia on conventional CT is limited. The goal of our study was to determine if virtual monochromatic CT increases the diagnostic accuracy for the detection of posterior infarcts relative to standard CT while using diffusion-weighted MRI as a reference standard. METHODS: Thirty consecutive subjects who meet the following inclusion criteria were retrospectively enrolled: (1) symptoms of posterior fossa stroke (e.g. vertigo, fainting, and dizziness), (2) unenhanced dual-energy CT of the head performed upon admission to the emergency department, and (3) MRI of the brain within 7 days following the CT. Eight of the 30 subjects were determined to have MRI diffusion-weighted imaging findings consistent with acute posterior fossa ischemia. Monochromatic energy reconstructions at 60, 80, 100, 120keV and the clinical CT were interpreted independently by two fellowship-trained neuroradiologists, who assessed the images for posterior fossa infarcts and for imaging quality. RESULTS: Reconstructions obtained at 80keV provided the best artifact reduction and overall maximization of image quality and were statistically significantly better than standard head CT (P<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were at least not less than standard CT, and there was a trend toward better values at 100keV (P=0.096). CONCLUSION: Monoenergetic 80 or 100keV reconstructions may improve the detection of posterior fossa ischemia compared to conventional CT. However, if clinical suspicion for posterior fossa ischemia warrants, a brain MRI with diffusion-weighted imaging should still be obtained, even in the presence of a negative dual energy CT of the brain. PMID- 27255680 TI - HIV-associated vasculopathy: Potential pitfall for IV thrombolysis and indication for vessel wall imaging. PMID- 27255681 TI - Colorectal cancer treatment and survival over three decades at four major public hospitals in South Australia: trends by age and in the elderly. AB - Data from registries at four major public hospitals in South Australia indicate increased 5-year disease-specific survivals for colorectal cancer from 48% to 63% between 1980-1986 and 2005-2010. For 80+ year olds, the increase was smaller, from 47% to 52%. Risk of case fatality halved overall, adjusting for age, gender, stage, differentiation and sub-site. Patients aged 80+ years had a lower risk reduction of about a third (hazards ratio: 0.69; 95% confidence limits, 0.52 0.92). Percentages having surgery and other specified treatments were lower for 80+ year olds than younger cases, although increases in treatment intensity occurred in this age range during 1980-2010, as seen in younger ages, in accordance with guidelines. The study illustrates the important feedback clinical registries can provide to clinicians on care patterns and outcomes in their hospital settings. Feedback can be the subject of local deliberations on how to achieve the best outcomes, including in the elderly by considering the best trade offs between optimal cancer care and accommodations for co-morbidity and frailty. Clinical registry data can be used in comparative effectiveness research in local settings where there are sufficient case numbers. PMID- 27255682 TI - Zika virus: oral health care and oral disease. PMID- 27255683 TI - Two New Highly Oxygenated Spirostanol Saponins from Paris polyphylla var. stenophylla. AB - Phytochemical investigation of the rhizomes of Paris polyphylla var. stenophylla led to the isolation of two new highly oxygenated spirostanol saponins, named paristenosides A (1) and B (2), together with seven known compounds. Their structures were established mainly on the base of NMR spectroscopic techniques and mass spectrometry, as well as chemical methods. In addition, the cytotoxicity of the two new saponins was tested. Two new highly oxygenated spirostanol saponins, paristenosides A (1) and B (2), were isolated from the rhizomes of Paris polyphylla var. stenophylla. Their structures were established mainly based on NMR spectroscopic techniques and mass spectrometry, as well as chemical methods. PMID- 27255685 TI - Associations Between Social Support, Social Networks, and Financial Exploitation in Older Adults. AB - Social support and social networks are important correlates of elder mistreatment. This study tests hypothesized associations between perceived social support, social network size, and financial exploitation (FE). A population-based survey of 903 older adults (60+) in Allegheny County (Pittsburgh, Pennsylvania) found that lower perceived social support and larger social networks were simultaneously associated with higher risk for FE since age 60, controlling for known risk factors. The same associations were found for FE in the last 6 months. Older adults with larger social networks combined with lower perceived social support were most likely to report FE. When it comes to the role of social relationships and risk for FE, "more may not always be better." Encouragement to widen the social network by "making new friends" should be stressed less than making sure these new network members will truly be supportive of the older adult. PMID- 27255686 TI - A New Tool for Assessing Mobile Device Proficiency in Older Adults: The Mobile Device Proficiency Questionnaire. AB - Mobile device proficiency is increasingly required to participate in society. Unfortunately, there still exists a digital divide between younger and older adults, especially with respect to mobile devices (i.e., tablet computers and smartphones). Training is an important goal to ensure that older adults can reap the benefits of these devices. However, efficient/effective training depends on the ability to gauge current proficiency levels. We developed a new scale to accurately assess the mobile device proficiency of older adults: the Mobile Device Proficiency Questionnaire (MDPQ). We present and validate the MDPQ and a short 16-question version of the MDPQ (MDPQ-16). The MDPQ, its subscales, and the MDPQ-16 were found to be highly reliable and valid measures of mobile device proficiency in a large sample. We conclude that the MDPQ and MDPQ-16 may serve as useful tools for facilitating mobile device training of older adults and measuring mobile device proficiency for research purposes. PMID- 27255687 TI - Comparison of shape memory polymer foam versus bare metal coil treatments in an in vivo porcine sidewall aneurysm model. AB - The endovascular delivery of platinum alloy bare metal coils has been widely adapted to treat intracranial aneurysms. Despite the widespread clinical use of this technique, numerous suboptimal outcomes are possible. These may include chronic inflammation, low volume filling, coil compaction, and recanalization, all of which can lead to aneurysm recurrence, need for retreatment, and/or potential rupture. This study evaluates a treatment alternative in which polyurethane shape memory polymer (SMP) foam is used as an embolic aneurysm filler. The performance of this treatment method was compared to that of bare metal coils in a head-to-head in vivo study utilizing a porcine vein pouch aneurysm model. After 90 and 180 days post-treatment, gross and histological observations were used to assess aneurysm healing. At 90 days, the foam-treated aneurysms were at an advanced stage of healing compared to the coil-treated aneurysms and showed no signs of chronic inflammation. At 180 days, the foam treated aneurysms exhibited an 89-93% reduction in cross-sectional area; whereas coiled aneurysms displayed an 18-34% area reduction. The superior healing in the foam-treated aneurysms at earlier stages suggests that SMP foam may be a viable alternative to current treatment methods. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1892-1905, 2017. PMID- 27255688 TI - Phase transformations during processing and in vitro degradation of porous calcium polyphosphates. AB - A 2-Step sinter/anneal treatment has been reported previously for forming porous CPP as biodegradable bone substitutes [9]. During the 2-Step annealing treatment, the heat treatment used strongly affected the rate of CPP degradation in vitro. In the present study, x-ray diffraction and (31)P solid state nuclear magnetic resonance were used to determine the phases that formed using different heat treating processes. The effect of in vitro degradation (in PBS at 37 degrees C, pH 7.1 or 4.5) was also studied. During CPP preparation, beta-CPP and gamma-CPP were identified in powders formed from a calcium monobasic monohydrate precursor after an initial calcining treatment (10 h at 500 degrees C). Melting of this CPP powder (at 1100 degrees C), quenching and grinding formed amorphous CPP powders. Annealing powders at 585 degrees C (Step-1) resulted in rapid sintering to form amorphous porous CPP. Continued annealing to 650 degrees C resulted in crystallization to form a multi-phase structure of beta-CPP primarily plus lesser amounts of alpha-CPP, calcium ultra-phosphates and retained amorphous CPP. Annealing above 720 degrees C and up to 950 degrees C transformed this to beta CPP phase. In vitro degradation of the 585 degrees C (Step-1 only) and 650 degrees C Step-2 annealed multi-phase samples occurred significantly faster than the beta-CPP samples formed by Step-2 annealing at or above 720 degrees C. This faster degradation was attributable to preferential degradation of thermodynamically less stable phases that formed in samples annealed at 650 degrees C (i.e. alpha-phase, ultra-phosphate and amorphous CPP). Degradation in lower pH solutions significantly increased degradation rates of the 585 and 650 degrees C annealed samples but had no significant effect on the beta-CPP samples. PMID- 27255689 TI - Terahertz radiation driven by two-color laser pulses at near-relativistic intensities: Competition between photoionization and wakefield effects. AB - We numerically investigate terahertz (THz) pulse generation by linearly polarized, two-color femtosecond laser pulses in highly-ionized argon. Major processes consist of tunneling photoionization and ponderomotive forces associated with transverse and longitudinal field excitations. By means of two dimensional particle-in-cell (PIC) simulations, we reveal the importance of photocurrent mechanisms besides transverse and longitudinal plasma waves for laser intensities >10(15) W/cm(2). We demonstrate the following. (i) With two color pulses, photoionization prevails in the generation of GV/m THz fields up to 10(17) W/cm(2) laser intensities and suddenly loses efficiency near the relativistic threshold, as the outermost electron shell of ionized Ar atoms has been fully depleted. (ii) PIC results can be explained by a one-dimensional Maxwell-fluid model and its semi-analytical solutions, offering the first unified description of the main THz sources created in plasmas. (iii) The THz power emitted outside the plasma channel mostly originates from the transverse currents. PMID- 27255690 TI - Impact of anastomotic leak on recurrence and survival after colorectal cancer surgery: a BioGrid Australia analysis. AB - BACKGROUND: There is conflicting evidence regarding the oncological impact of anastomotic leak following colorectal cancer surgery. This study aims to test the hypothesis that anastomotic leak is independently associated with local recurrence and overall and cancer-specific survival. METHODS: Analysis of prospectively collected data from multiple centres in Victoria between 1988 and 2015 including all patients who underwent colon or rectal resection for cancer with anastomosis was presented. Overall and cancer-specific survival rates and rates of local recurrence were compared using Cox regression analysis. RESULTS: A total of 4892 patients were included, of which 2856 had completed 5-year follow up. The overall anastomotic leak rate was 4.0%. Cox regression analysis accounting for differences in age, sex, body mass index, American Society of Anesthesiologists score and tumour stage demonstrated that anastomotic leak was associated with significantly worse 5-year overall survival (chi 2 = 6.459, P = 0.011) for colon cancer, but only if early deaths were included. There was no difference in 5-year colon cancer-specific survival (chi 2 = 0.582, P = 0.446) or local recurrence (chi 2 = 0.735, P = 0.391). For rectal cancer, there was no difference in 5-year overall survival (chi 2 = 0.266, P = 0.606), cancer-specific survival (chi 2 = 0.008, P = 0.928) or local recurrence (chi 2 = 2.192, P = 0.139). CONCLUSION: Anastomotic leak may reduce 5-year overall survival in colon cancer patients but does not appear to influence the 5-year overall survival in rectal cancer patients. There was no effect on local recurrence or cancer specific survival. PMID- 27255691 TI - Cataract surgery in patients with neovascular age-related macular degeneration. AB - PURPOSE: To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti vascular endothelial growth factor (VEGF) injections in routine clinical practice. METHODS: We extracted information about patients recorded in electronic databases managing anti-VEGF injections and cataract surgery. We compared Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and frequency of anti-VEGF injections before and after cataract surgery. RESULTS: We identified 89 eyes from 89 patients who had cataract surgery after being treated with a median of 10 (range 3-36) anti-VEGF injections for neovascular AMD. Visual acuity improved by a mean of 7.1 [95% confidence interval (CI) 4.6-9.6] ETDRS letters in the first 6 months after cataract surgery. The need of anti-VEGF injections did not change after cataract surgery with an average of 1.5 in the 6 months before surgery versus 1.7 in the 6 months after surgery (p = 0.25). Visual improvement was greater in patients when the time from latest injection to cataract surgery was lower. CONCLUSIONS: Cataract surgery improves vision in patients undergoing treatment for neovascular AMD. Cataract surgery was not associated with an increased need for anti-VEGF treatment and patients who were in active anti-VEGF treatment had better visual outcomes than patients who had cataract surgery after long injection-free periods. PMID- 27255692 TI - The dynamic experience of pain in burn patients: A phenomenological study. AB - Although pain is one of the main sources of suffering during the acute phase and rehabilitation in burn patients, it remains as a major challenge for burn care, and clinical management not always correlates with the experience felt by patients. The aim of this study was to understand the experience of pain from people who has suffered severe burns, to identify personal strategies used to cope with this challenging event. A qualitative phenomenological study with purposive sampling was carried out with severe burn patients admitted to a Burn Unit. Through individual in-depth interviews, verbatim transcription and content analysis, two main categories were isolated: a dynamic and changing experience of pain, from the onset to the hospital discharge, and diverse strategies developed by patients to cope with pain, being distraction the most frequently used. Pain experienced acquires its maximum intensity during wound care, and divergent patients' opinions about sedation are present. This study highlights how understanding subjective experiences is an invaluable aid to improve care in pain assessment and management. Furthermore, it points out the need to guarantee patient involvement in the organization and improvement of burn care, inasmuch as traditional professional centered approach is not ensuring an optimal management. PMID- 27255693 TI - MEF2C haploinsufficiency syndrome: Report of a new MEF2C mutation and review. AB - INTRODUCTION: MEF2C haploinsufficiency syndrome is characterized by severe intellectual disability, epilepsy, stereotypic movements, minor dysmorphisms and brain abnormalities. We report the case of a patient with a new MEF2C mutation, comparing his clinical and imaging features to those previously reported in the literature. CASE REPORT: A 10 year-old boy first came to pediatric neurology clinic at the age of 11 months because of severe psychomotor delay, without regression. He presented generalized hypotonia, poor eye contact, hand-mouth stereotypies, strabismus and minor facial dimorphisms. Epileptic seizures started at 26 months of age and were refractory. Brain MRI showed a slight increase in periventricular white matter signal and globally enlarged CSF spaces. Molecular analysis revealed a de novo, pathogenic and causative MEF2C mutation. DISCUSSION: MEF2C haploinsufficiency syndrome was recently recognized as a neurodevelopmental disorder. Severe intellectual disability with inability to speak and epilepsy are universal features in patients with MEF2C mutations, although mild cognitive and speech disorders have been reported to occur in patients with duplications. Epilepsy might be absent in patients with partial deletions. Abnormal movement patterns are very common in patients with MEF2C haploinsufficiency. Delayed myelination seems to be more commonly observed in patients with MEF2C mutations, while malformations of cortical development were only reported in patients with microdeletions. Although MEF2C haploinsufficiency prevalence is yet to be determined, it should be considered in the differential diagnosis of patients with severe intellectual disability and Rett-like features. PMID- 27255694 TI - The similarity of life across the universe. AB - Is the hypothesis correct that if life exists elsewhere in the universe, it would have forms and structures unlike anything we could imagine? From the subatomic level in cellular energy acquisition to the assembly and even behavior of organisms at the scale of populations, life on Earth exhibits characteristics that suggest it is a universal norm for life at all levels of hierarchy. These patterns emerge from physical and biochemical limitations. Their potentially universal nature is supported by recent data on the astrophysical abundance and availability of carbon compounds and water. Within these constraints, biochemical and biological variation is certainly possible, but it is limited. If life exists elsewhere, life on Earth, rather than being a contingent product of one specific experiment in biological evolution, is likely to reflect common patterns for the assembly of living matter. PMID- 27255696 TI - Towards a nanospecific approach for risk assessment. AB - In the current paper, a new strategy for risk assessment of nanomaterials is described, which builds upon previous project outcomes and is developed within the FP7 NANoREG project. NANoREG has the aim to develop, for the long term, new testing strategies adapted to a high number of nanomaterials where many factors can affect their environmental and health impact. In the proposed risk assessment strategy, approaches for (Quantitative) Structure Activity Relationships ((Q)SARs), grouping and read-across are integrated and expanded to guide the user how to prioritise those nanomaterial applications that may lead to high risks for human health. Furthermore, those aspects of exposure, kinetics and hazard assessment that are most likely to be influenced by the nanospecific properties of the material under assessment are identified. These aspects are summarised in six elements, which play a key role in the strategy: exposure potential, dissolution, nanomaterial transformation, accumulation, genotoxicity and immunotoxicity. With the current approach it is possible to identify those situations where the use of nanospecific grouping, read-across and (Q)SAR tools is likely to become feasible in the future, and to point towards the generation of the type of data that is needed for scientific justification, which may lead to regulatory acceptance of nanospecific applications of these tools. PMID- 27255695 TI - Engineering therapeutic protein disaggregases. AB - Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., alpha-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID- 27255697 TI - Globus pallidus degeneration and clinicopathological features of Huntington disease. AB - OBJECTIVE: Numerous studies have focused on striatal neurodegeneration in Huntington disease (HD). In comparison, the globus pallidus (GP), a main striatal output nucleus, has received less focus in HD research. This study characterizes the pattern of neurodegeneration in 3 subdivisions of the human GP, and its relation to clinical symptomatology. METHODS: Stereology was used to measure regional atrophy, neuronal loss, and soma neuronal atrophy in 3 components of the GP-the external segment (GPe), internal segment (GPi), and ventral pallidum (VP) in 8 HD cases compared with 7 matched control cases. The findings in the HD patients were compared with HD striatal neuropathological grade, and symptom scores of motor impairment, chorea, cognition, and mood. RESULTS: Relative to controls, in the HD patients the GPe showed a 54% overall volume decline, 60% neuron loss, and 34% reduced soma volume. Similarly, the VP was reduced in volume by 31%, with 48% neuron loss and 64% reduced soma volume. In contrast, the GPi was less affected, with a 38% reduction in overall volume only. The extent of GP neurodegeneration correlated with increasing striatal neuropathological grade. Decreasing GPe and VP volumes were associated with poorer cognition and increasing motor impairments, but not chorea. In contrast, decreasing GPi volumes were associated with decreasing levels of irritability. INTERPRETATION: The HD gene mutation produces variable degrees of GP segment degeneration, highlighting the differential vulnerability of striato-GP target projections. The relationship established between clinical symptom scores and pallidal degeneration provides a novel contribution to understanding the clinicopathological associations in HD. Ann Neurol 2016;80:185-201. PMID- 27255698 TI - Most stomatal closure in woody species under moderate drought can be explained by stomatal responses to leaf turgor. AB - Reduced stomatal conductance (gs ) during soil drought in angiosperms may result from effects of leaf turgor on stomata and/or factors that do not directly depend on leaf turgor, including root-derived abscisic acid (ABA) signals. To quantify the roles of leaf turgor-mediated and leaf turgor-independent mechanisms in gs decline during drought, we measured drought responses of gs and water relations in three woody species (almond, grapevine and olive) under a range of conditions designed to generate independent variation in leaf and root turgor, including diurnal variation in evaporative demand and changes in plant hydraulic conductance and leaf osmotic pressure. We then applied these data to a process based gs model and used a novel method to partition observed declines in gs during drought into contributions from each parameter in the model. Soil drought reduced gs by 63-84% across species, and the model reproduced these changes well (r(2) = 0.91, P < 0.0001, n = 44) despite having only a single fitted parameter. Our analysis concluded that responses mediated by leaf turgor could explain over 87% of the observed decline in gs across species, adding to a growing body of evidence that challenges the root ABA-centric model of stomatal responses to drought. PMID- 27255699 TI - Diuretic and serum electrolyte regulation potential of aqueous methanolic extract of Solanum surattense fruit validates its folkloric use in dysuria. AB - BACKGROUND: Solanum surattense Burm. (Solanaceae) is traditionally used for management of various ailments. The study was conducted for provision of pharmacological justification for folkloric uses of Solanum surattense in the treatment of dysuria. METHODS: Rats were randomly divided into 5 groups, each of (n = 6). Aqueous methanolic fruit extract of S. surattense were also administered intraperitoneally to the rats at doses of 50, 70 and 100 mg/kg. Furosemide (10 mg/kg i.p) was used as standard drug whereas controls were given saline solution (40 mL/kg i.p). The electrolytes in urine were measured using a flame photometer whereas serum sodium, potassium, calcium, bicarbonate and blood urea nitrogen (BUN) were determined by using an automatic analyzer. Urine osmolality was assayed by the micro-osmometer. RESULTS: The extract S. surattense induced diuretic effects in a dose-dependent manner as compared with control. Upon administration of extract (70 and 100 mg/kg), we observed the prominent (p < 0.01) increase in the urine volume and osmolality in comparison to control group. However, plant extract (100 mg/kg) significantly increase the urinary electrolyte excretion especially calcium (p < 0.05) to that of the furosemide whereas level of magnesium remains constant. Moreover, our results showed a decrease in serum levels of sodium, potassium, calcium and blood urea nitrogen (BUN), but concentration dependent increase in bicarbonate was found in the test groups. There was no substantial change in the pH of urine samples of the extract-treated groups. CONCLUSION: These results indicate that S. surattense investigated exert its action by causing diuresis in the treatment of dysuria. PMID- 27255700 TI - Hypersomatotropism in 3 Cats without Concurrent Diabetes Mellitus. PMID- 27255701 TI - Ectomycorrhizal and saprotrophic fungi respond differently to long-term experimentally increased snow depth in the High Arctic. AB - Changing climate is expected to alter precipitation patterns in the Arctic, with consequences for subsurface temperature and moisture conditions, community structure, and nutrient mobilization through microbial belowground processes. Here, we address the effect of increased snow depth on the variation in species richness and community structure of ectomycorrhizal (ECM) and saprotrophic fungi. Soil samples were collected weekly from mid-July to mid-September in both control and deep snow plots. Richness of ECM fungi was lower, while saprotrophic fungi was higher in increased snow depth plots relative to controls. [Correction added on 23 September 2016 after first online publication: In the preceding sentence, the richness of ECM and saprotrophic fungi were wrongly interchanged and have been fixed in this current version.] ECM fungal richness was related to soil NO3 N, NH4 -N, and K; and saprotrophic fungi to NO3 -N and pH. Small but significant changes in the composition of saprotrophic fungi could be attributed to snow treatment and sampling time, but not so for the ECM fungi. Delayed snow melt did not influence the temporal variation in fungal communities between the treatments. Results suggest that some fungal species are favored, while others are disfavored resulting in their local extinction due to long-term changes in snow amount. Shifts in species composition of fungal functional groups are likely to affect nutrient cycling, ecosystem respiration, and stored permafrost carbon. PMID- 27255702 TI - Longitudinal comparative evaluation of the equivalence of an integrated peer support and clinical staffing model for residential mental health rehabilitation: a mixed methods protocol incorporating multiple stakeholder perspectives. AB - BACKGROUND: A novel staffing model integrating peer support workers and clinical staff within a unified team is being trialled at community based residential rehabilitation units in Australia. A mixed-methods protocol for the longitudinal evaluation of the outcomes, expectations and experiences of care by consumers and staff under this staffing model in two units will be compared to one unit operating a traditional clinical staffing. The study is unique with regards to the context, the longitudinal approach and consideration of multiple stakeholder perspectives. METHODS/DESIGN: The longitudinal mixed methods design integrates a quantitative evaluation of the outcomes of care for consumers at three residential rehabilitation units with an applied qualitative research methodology. The quantitative component utilizes a prospective cohort design to explore whether equivalent outcomes are achieved through engagement at residential rehabilitation units operating integrated and clinical staffing models. Comparative data will be available from the time of admission, discharge and 12-month period post-discharge from the units. Additionally, retrospective data for the 12-month period prior to admission will be utilized to consider changes in functioning pre and post engagement with residential rehabilitation care. The primary outcome will be change in psychosocial functioning, assessed using the total score on the Health of the Nation Outcome Scales (HoNOS). Planned secondary outcomes will include changes in symptomatology, disability, recovery orientation, carer quality of life, emergency department presentations, psychiatric inpatient bed days, and psychological distress and wellbeing. Planned analyses will include: cohort description; hierarchical linear regression modelling of the predictors of change in HoNOS following CCU care; and descriptive comparisons of the costs associated with the two staffing models. The qualitative component utilizes a pragmatic approach to grounded theory, with collection of data from consumers and staff at multiple time points exploring their expectations, experiences and reflections on the care provided by these services. DISCUSSION: It is expected that the new knowledge gained through this study will guide the adaptation of these and similar services. For example, if differential outcomes are achieved for consumers under the integrated and clinical staffing models this may inform staffing guidelines. PMID- 27255703 TI - Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice. AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments. PMID- 27255704 TI - Long Pauses in Cerebellar Interneurons in Anesthetized Animals. AB - Are long pauses in the firing of cerebellar interneurons (CINs) related to Purkinje cell (PC) pauses? If PC pauses affect the larger network, then we should find a close relationship between CIN pauses and those in PCs. We recorded activity of 241 cerebellar cortical neurons (206 CINs and 35 PCs) in three anesthetized cats. One fifth of the CINs and more than half of the PCs were identified as pausing. Pauses in CINs and PCs showed some differences: CIN mean pause length was shorter, and, after pauses, only CINs had sustained reduction in their firing rate (FR). Almost all pausing CINs fell into same cluster when we used different methods of clustering CINs by their spontaneous activity. The mean spontaneous firing rate of that cluster was approximately 53 Hz. We also examined cross-correlations in simultaneously recorded neurons. Of 39 cell pairs examined, 14 (35 %) had cross-correlations significantly different from those expected by chance. Almost half of the pairs with two CINs showed statistically significant negative correlations. In contrast, PC/CIN pairs did not often show significant effects in the cross-correlation (12/15 pairs). However, for both CIN/CIN and PC/CIN pairs, pauses in one unit tended to correspond to a reduction in the firing rate of the adjacent unit. In our view, our results support the possibility that previously reported PC bistability is part of a larger network response and not merely a biophysical property of PCs. Any functional role for PC bistability should probably be sought in the context of the broader network. PMID- 27255705 TI - Cerebellar Changes in Guinea Pig Offspring Following Suppression of Neurosteroid Synthesis During Late Gestation. AB - Elevated gestational concentrations of allopregnanolone are essential for the development and neuroprotection of the foetal brain. Preterm birth deprives the foetus of these high levels of allopregnanolone, which may contribute to the associated adverse effects on cerebellar development. Preterm birth alters expression of GABAA receptor subunit composition, which may further limit neurosteroid action. The objective of this study was to determine the effects of suppression of allopregnanolone levels on the markers of development and functional outcome. Pregnant guinea pigs were treated with finasteride at a dose (25 mg/kg maternal weight) shown to suppress allopregnanolone between 60 days of gestation until delivery (term ~71 days). The cerebella from neonates, whose mothers were treated with finasteride or vehicle during pregnancy, were collected at postnatal age 8. Pups that received finasteride displayed significantly greater glial fibrillary acid protein area coverage and reduced GABAA receptor alpha6-subunit messenger RNA within the cerebellum than pups that were exposed to vehicle. These findings indicate that loss of neurosteroid action on the foetal brain in late gestation produces prolonged astrocyte activation and reductions in GABAA receptor alpha6-subunit expression. These changes may contribute to the long-term changes in function associated with preterm birth. PMID- 27255706 TI - Diffusion Tensor Tractography of the Cerebellar Peduncles in Prematurely Born 7 Year-Old Children. AB - The objective of this study was to correlate neurodevelopmental outcome of preterm-born children and their perinatal clinical and imaging characteristics with diffusion magnetic resonance imaging (MRI) measures of the three cerebellar peduncles at age 7. Included in this prospective longitudinal study were 140 preterm-born children (<30 weeks gestation) who underwent neurodevelopmental assessment (IQ, motor, language, working memory) and diffusion-weighted imaging (DWI) at age 7 years. White matter tracts in the superior, middle, and inferior cerebellar peduncles were delineated using regions of interest drawn on T2 weighted images and fractional anisotropy (FA) maps. Diffusion measures (mean diffusivity (MD) and FA) and tract volumes were calculated. Linear regression was used to assess relationships with outcome. The severity of white matter injury in the neonatal period was associated with lower FA in the right superior cerebellar peduncle (SCP) and lower tract volumes of both SCPs and middle cerebellar peduncles (MCPs). In the MCP, higher IQ was associated with lower MD in the whole group and higher FA in right-handed children. In the SCP, lower motor scores were associated with higher MD and higher language scores were associated with higher FA. These associations remained significant in multivariable models. This study adds to the body of literature detailing the importance of cerebellar involvement in cognitive function related to reciprocal connections with supratentorial structures. PMID- 27255707 TI - Selection of affinity-improved neutralizing human scFv against HBV PreS1 from CDR3 VH/VL mutant library. AB - A CDR3 mutant library was constructed from a previously isolated anti-HBV neutralizing Homo sapiens scFv-31 template by random mutant primers PCR. Then the library was displayed on the inner membrane surface in Escherichia coli periplasmic space. Seven scFv clones were isolated from the mutant library through three rounds of screening by flow cytometry. Competition ELISA assay indicates that isolated scFv fragments show more efficient binding ability to HBV PreS1 compared with parental scFv-31. HBV neutralization assay indicated that two clones (scFv-3 and 59) show higher neutralizing activity by blocking the HBV infection to Chang liver cells. Our method provides a new strategy for rapid screening of mutant antibody library for affinity-enhanced scFv clones and the neutralizing scFvs obtained from this study provide a potential alternative of Hepatitis B immune globulin. PMID- 27255708 TI - Possible involvement of hippocampal immediate-early genes in contextual fear memory deficit induced by cranial irradiation. AB - Cranial irradiation can trigger adverse effects on brain functions, including cognitive ability. However, the cellular and molecular mechanisms underlying radiation-induced cognitive impairments remain still unknown. Immediate-early genes (IEGs) are implicated in neuronal plasticity and the related functions (i.e., memory formation) in the hippocampus. The present study quantitatively assessed changes in the mRNA and protein levels of the learning-induced IEGs, including Arc, c-fos, and zif268, in the mouse hippocampus after cranial irradiation using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. Mice (male, 8-week-old C57BL/6) received whole-brain irradiation with 0 or 10Gy of gamma-ray and, 2weeks later, contextual fear conditioning (CFC) was used to induce IEGs. In the CFC task, mice evaluated 2weeks after irradiation exhibited significant memory deficits compared with sham (0Gy)-irradiated controls. The levels of mRNA encoding IEGs were significantly upregulated in the hippocampus 10 and 30min after CFC training. The mRNA levels in the irradiated hippocampi were significantly lower than those in the sham-irradiated controls. The IEG protein levels were significantly increased in all hippocampal regions, including the hippocampal dentate gyrus, cornu ammonis (CA)1, and CA3, after CFC training. The CFC-induced upregulation of Arc and c-fos in 10Gy-irradiated hippocampi was significantly lower than that in sham-irradiated controls, although there were no significant differences in the protein levels of the learning-induced zif268 between sham-irradiated and 10Gy-irradiated hippocampi. Thus, cranial irradiation with 10Gy of gamma-ray impairs the induction of hippocampal IEGs (particularly Arc and c-fos) via behavioral contextual fear memory, and this disturbance may be associated with the memory deficits evident in mice after cranial irradiation, possibly through the dysregulation of neuronal plasticity during memory formation. PMID- 27255710 TI - Short Term Palmitate Supply Impairs Intestinal Insulin Signaling via Ceramide Production. AB - The worldwide prevalence of metabolic diseases is increasing, and there are global recommendations to limit consumption of certain nutrients, especially saturated lipids. Insulin resistance, a common trait occurring in obesity and type 2 diabetes, is associated with intestinal lipoprotein overproduction. However, the mechanisms by which the intestine develops insulin resistance in response to lipid overload remain unknown. Here, we show that insulin inhibits triglyceride secretion and intestinal microsomal triglyceride transfer protein expression in vivo in healthy mice force-fed monounsaturated fatty acid-rich olive oil but not in mice force-fed saturated fatty acid-rich palm oil. Moreover, when mouse intestine and human Caco-2/TC7 enterocytes were treated with the saturated fatty acid, palmitic acid, the insulin-signaling pathway was impaired. We show that palmitic acid or palm oil increases ceramide production in intestinal cells and that treatment with a ceramide analogue partially reproduces the effects of palmitic acid on insulin signaling. In Caco-2/TC7 enterocytes, ceramide effects on insulin-dependent AKT phosphorylation are mediated by protein kinase C but not by protein phosphatase 2A. Finally, inhibiting de novo ceramide synthesis improves the response of palmitic acid-treated Caco-2/TC7 enterocytes to insulin. These results demonstrate that a palmitic acid-ceramide pathway accounts for impaired intestinal insulin sensitivity, which occurs within several hours following initial lipid exposure. PMID- 27255709 TI - Molecular Mechanism of Mot1, a TATA-binding Protein (TBP)-DNA Dissociating Enzyme. AB - The essential Saccharomyces cerevisiae ATPase Mot1 globally regulates transcription by impacting the genomic distribution and activity of the TATA binding protein (TBP). In vitro, Mot1 forms a ternary complex with TBP and DNA and can use ATP hydrolysis to dissociate the TBP-DNA complex. Prior work suggested an interaction between the ATPase domain and a functionally important segment of DNA flanking the TATA sequence. However, how ATP hydrolysis facilitates removal of TBP from DNA is not well understood, and several models have been proposed. To gain insight into the Mot1 mechanism, we dissected the role of the flanking DNA segment by biochemical analysis of complexes formed using DNAs with short single-stranded gaps. In parallel, we used a DNA tethered cleavage approach to map regions of Mot1 in proximity to the DNA under different conditions. Our results define non-equivalent roles for bases within a broad segment of flanking DNA required for Mot1 action. Moreover, we present biochemical evidence for two distinct conformations of the Mot1 ATPase, the detection of which can be modulated by ATP analogs as well as DNA sequence flanking the TATA sequence. We also show using purified complexes that Mot1 dissociation of a stable, high affinity TBP-DNA interaction is surprisingly inefficient, suggesting how other transcription factors that bind to TBP may compete with Mot1. Taken together, these results suggest that TBP-DNA affinity as well as other aspects of promoter sequence influence Mot1 function in vivo. PMID- 27255711 TI - Structural Basis of the Recruitment of Ubiquitin-specific Protease USP15 by Spliceosome Recycling Factor SART3. AB - Ubiquitin-specific proteases (USPs) USP15 and USP4 belong to a subset of USPs featuring an N-terminal tandem domain in USP (DUSP) and ubiquitin-like (UBL) domain. Squamous cell carcinoma antigen recognized by T-cell 3 (SART3), a spliceosome recycling factor, binds to the DUSP-UBL domain of USP15 and USP4, recruiting them to the nucleus from the cytosol to control deubiquitination of histone H2B and spliceosomal proteins, respectively. To provide structural insight, we solved crystal structures of SART3 in the apo-form and in complex with the DUSP-UBL domain of USP15 at 2.0 and 3.0 A, respectively. Structural analysis reveals SART3 contains 12 half-a-tetratricopeptide (HAT) repeats, organized into two subdomains, HAT-N and HAT-C. SART3 dimerizes through the concave surface of HAT-C, whereas the HAT-C convex surface binds USP15 in a novel bipartite mode. Isothermal titration calorimetry measurements and mutagenesis analysis confirmed key residues of USP15 involved in the interaction and indicated USP15 binds 20-fold stronger than USP4. PMID- 27255712 TI - Phosphorylation of Deinococcus radiodurans RecA Regulates Its Activity and May Contribute to Radioresistance. AB - Deinococcus radiodurans has a remarkable capacity to survive exposure to extreme levels of radiation that cause hundreds of DNA double strand breaks (DSBs). DSB repair in this bacterium depends on its recombinase A protein (DrRecA). DrRecA plays a pivotal role in both extended synthesis-dependent strand annealing and slow crossover events of DSB repair during the organism's recovery from DNA damage. The mechanisms that control DrRecA activity during the D. radiodurans response to gamma radiation exposure are unknown. Here, we show that DrRecA undergoes phosphorylation at Tyr-77 and Thr-318 by a DNA damage-responsive serine threonine/tyrosine protein kinase (RqkA). Phosphorylation modifies the activity of DrRecA in several ways, including increasing its affinity for dsDNA and its preference for dATP over ATP. Strand exchange reactions catalyzed by phosphorylated versus unphosphorylated DrRecA also differ. In silico analysis of DrRecA structure support the idea that phosphorylation can modulate crucial functions of this protein. Collectively, our findings suggest that phosphorylation of DrRecA enables the recombinase to selectively use abundant dsDNA substrate present during post-irradiation recovery for efficient DSB repair, thereby promoting the extraordinary radioresistance of D. radiodurans. PMID- 27255714 TI - Is the Annual Confidential Report system effective? A study of the government appraisal system in Gujarat, India. AB - BACKGROUND: Effective performance appraisal systems can not only motivate employees to improve performance but also be important for the performance of organizations. However, the appraisal systems in civil services called the Annual Confidential Report (ACR) systems can be ineffective and do not contribute to employees' learning and development. With this background, the current study aimed at understanding the ACR system and assessing its effectiveness. The research aims to contribute in filling the knowledge gap in the existing literature on the need as to why the ACR system in civil services is an important human resource management (HRM) function. METHODS: The analysis is based on policy review to understand the extant appraisal-related rules and policies. Nineteen in-depth interviews with medical officers (MOs) working with the government health department of Gujarat, India, were conducted. The main objective of the research was to assess the effectiveness of the actual appraisal system called or referred to as the ACR as perceived by MOs. Thematic framework approach was used to analyze qualitative data using NVIVO 9. Themes were built around five features of an effective appraisal system, i.e., purpose, source, feedback quality, link of the ACR system with other human resource functions, and administrative effectiveness. RESULTS: The five features of the effective appraisal system studied in the current research (purpose, source, feedback quality, link of ACR system with other HRM functions, and administrative effectiveness) indicate that the overall appraisal system is ineffective. The overall appraisal system was perceived to be subjective and one directional in character by the study respondents. Furthermore, respondents perceived the appraisal system to be a ritual and where MOs hardly got to know about their performance, especially good performance. Hence, the feedback loop, an important feature for an effective appraisal system, was absent. The overall ACR system functions in isolation with no link to other HRM functions such as training and counselling, and a weak link with salary administration and promotion. CONCLUSIONS: Addressing the five features or domains of an effective appraisal system can lead to improved perceived fairness MOs have on the current appraisal system which may further influence the satisfaction and motivation positively. Improved motivation and satisfaction with the appraisal system can influence two important human resource for health-related outcomes, i.e., performance and retention. PMID- 27255715 TI - Theory of mind grows up: Reflections on new research on theory of mind in middle childhood and adolescence. PMID- 27255713 TI - Drug Treatment of Venous Thromboembolism in the Elderly. AB - Half of all patients with acute venous thromboembolism are aged over 70 years; they then face the added hazard of an age-related increase in the incidence of major bleeding. This makes it even more important to weigh the balance of benefit and risk when considering anticoagulant treatment and treatment duration. Traditional treatment with a heparin (usually low molecular weight) followed by a vitamin K antagonist such as warfarin is effective but is often complicated, especially in the elderly. The direct-acting oral anticoagulants (DOACs), i.e. the thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban and edoxaban, are given in fixed doses, do not need laboratory monitoring, have fewer drug-drug interactions and are therefore much easier to take. Randomised trials, their meta-analyses and 'real-world' data indicate the DOACs are no less effective than warfarin (are non-inferior) and probably cause less major bleeding (especially intracranial). It seems the relative safety of DOACs extends to age above 65 or 70 years, although bleeding becomes more likely regardless of the chosen anticoagulant. Renal impairment, comorbidities (especially cancer) and interventions are special hazards. Ways to minimise bleeding include patient selection and follow-up, education about venous thromboembolism, anticoagulants, drug interactions, regular checks on adherence and avoiding needlessly prolonged treatment. The relatively short circulating half-lives of DOACs mean that time, local measures and supportive care are the main response to major bleeding. They also simplify the management of invasive interventions. An antidote for dabigatran, idarucizumab, was recently approved by regulators, and a general antidote for factor Xa inhibitors is in advanced development. PMID- 27255716 TI - Extensive coronavirus-induced membrane rearrangements are not a determinant of pathogenicity. AB - Positive-strand RNA (+RNA) viruses rearrange cellular membranes during replication, possibly in order to concentrate and arrange viral replication machinery for efficient viral RNA synthesis. Our previous work showed that in addition to the conserved coronavirus double membrane vesicles (DMVs), Beau-R, an apathogenic strain of avian Gammacoronavirus infectious bronchitis virus (IBV), induces regions of ER that are zippered together and tethered open-necked double membrane spherules that resemble replication organelles induced by other +RNA viruses. Here we compared structures induced by Beau-R with the pathogenic lab strain M41 to determine whether membrane rearrangements are strain dependent. Interestingly, M41 was found to have a low spherule phenotype. We then compared a panel of pathogenic, mild and attenuated IBV strains in ex vivo tracheal organ culture (TOC). Although the low spherule phenotype of M41 was conserved in TOCs, each of the other tested IBV strains produced DMVs, zippered ER and spherules. Furthermore, there was a significant correlation for the presence of DMVs with spherules, suggesting that these structures are spatially and temporally linked. Our data indicate that virus induced membrane rearrangements are fundamentally linked to the viral replicative machinery. However, coronavirus replicative apparatus clearly has the plasticity to function in different structural contexts. PMID- 27255717 TI - Serum HER2 extracellular domain levels and HER2 circulating tumor cell status in patients with metastatic breast cancer. AB - AIM: To shed light on the clinical role of HER2 status in serum as extracellular domain (ECD) and corresponding circulating tumor cells (CTCs) in metastatic breast cancer patients. METHODS: 68 patients were analyzed. Serum HER2 was determined by ADVIA Centaur((r)) Serum HER2 test. CellSearch System was performed for CTC quantification. RESULTS: HER2 was overexpressed in 21 primary tumors. In total, 19 patients had ECD >15 ng/ml (the cut-off used), 48 patients had at least one CTC. ECD positivity was associated with CTC number (p = 0.01), HER2-positive CTC (p = 0.01) and the ratio HER2-positive CTC/total CTC (p = 0.02). ECD was not associated with survival. CONCLUSION: ECD in combination with HER2 CTC status would deserve further investigation in larger series for addressing its putative prognostic relevance. PMID- 27255718 TI - CORRIGENDUM. PMID- 27255721 TI - Letter to the Editor: Comment on "Thyroid stimulating antibodies are highly prevalent in Hashimoto thyroiditis and associated orbitopathy" Dear Editor. PMID- 27255722 TI - Response, Letter to the Editor: Author Response to Mustafa Sahin. PMID- 27255723 TI - Letter to the Editor: Association Between Body Mass Index and Hip Fragility in Older Adults. PMID- 27255724 TI - Vitamin D Deficiency Accelerates Coronary Artery Disease Progression in Swine. AB - OBJECTIVE: The role of vitamin D deficiency in coronary artery disease (CAD) progression is uncertain. Chronic inflammation in epicardial adipose tissue (EAT) has been implicated in the pathogenesis of CAD. However, the molecular mechanism underlying vitamin D deficiency-enhanced inflammation in the EAT of diseased coronary arteries remains unknown. We examined a mechanistic link between 1,25 dihydroxyvitamin D-mediated suppression of nuclear factor-kappaB (NF-kappaB) transporter, karyopherin alpha4 (KPNA4) expression and NF-kappaB activation in preadipocytes. Furthermore, we determined whether vitamin D deficiency accelerates CAD progression by increasing KPNA4 and nuclear NF-kappaB levels in EAT. APPROACH AND RESULTS: Nuclear protein levels were detected by immunofluorescence and Western blot. Exogenous KPNA4 was transported into cells by a transfection approach and constituted lentiviral vector. Swine were administered vitamin D-deficient or vitamin D-sufficient hypercholesterolemic diet. After 1 year, the histopathology of coronary arteries and nuclear protein expression of EAT were assessed. 1,25-dihydroxyvitamin D inhibited NF-kappaB activation and reduced KPNA4 levels through increased vitamin D receptor expression. Exogenous KPNA4 rescued 1,25-dihydroxyvitamin D-dependent suppression of NF-kappaB nuclear translocation and activation. Vitamin D deficiency caused extensive CAD progression and advanced atherosclerotic plaques, which are linked to increased KPNA4 and nuclear NF-kappaB levels in the EAT. CONCLUSIONS: 1,25 dihydroxyvitamin D attenuates NF-kappaB activation by targeting KPNA4. Vitamin D deficiency accelerates CAD progression at least, in part, through enhanced chronic inflammation of EAT by upregulation of KPNA4, which enhances NF-kappaB activation. These novel findings provide mechanistic evidence that vitamin D supplementation could be beneficial for the prevention and treatment of CAD. PMID- 27255726 TI - Catatonia. AB - One of the most exciting psychiatric conditions is the bizarre psychomotor syndrome called catatonia, which may present with a large number of different motor signs and even vegetative instability. Catatonia is potentially life threatening. The use of benzodiazepines and electroconvulsive therapy (ECT) has been efficient in the majority of patients. The rich clinical literature of the past has attempted to capture the nature of catatonia. But the lack of diagnostic clarity and operationalization has hampered research on catatonia for a long time. Within the last decades, it became clear that catatonia had to be separated from schizophrenia, which was finally accomplished in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). In DSM-5, catatonia syndrome may be diagnosed as a specifier to major mood disorders, psychotic disorders, general medical conditions, and as catatonia not otherwise specified. This allows diagnosing the syndrome in a large variety of psychiatric disorders. Currently, the pathobiology remains widely unknown. Suspected neurotransmitter systems include gamma-aminobutyric acid (GABA) and glutamate. Neuroimaging reports pointed to reduced resting state activity and reduced task activation in motor areas of the frontal and parietal cortex. The new classification of catatonia will foster more clinical research and neuroscientific approaches by testing catatonia in various populations and applying stringent criteria. The scarce number of prospective trials will hopefully increase, as more trials will be encouraged within a more precise concept of catatonia. PMID- 27255725 TI - Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone. AB - OBJECTIVE: Myogenic tone (MT) of resistance arteries ensures autoregulation of blood flow in organs and relies on the intrinsic property of smooth muscle to contract in response to stretch. Nucleotides released by mechanical strain on cells are responsible for pleiotropic vascular effects, including vasoconstriction. Here, we evaluated the contribution of extracellular nucleotides to MT. APPROACH AND RESULTS: We measured MT and the associated pathway in mouse mesenteric resistance arteries using arteriography for small arteries and molecular biology. Of the P2 receptors in mouse mesenteric resistance arteries, mRNA expression of P2X1 and P2Y6 was dominant. P2Y6 fully sustained UDP/UTP-induced contraction (abrogated in P2ry6(-/-) arteries). Preventing nucleotide hydrolysis with the ectonucleotidase inhibitor ARL67156 enhanced pressure-induced MT by 20%, whereas P2Y6 receptor blockade blunted MT in mouse mesenteric resistance arteries and human subcutaneous arteries. Despite normal hemodynamic parameters, P2ry6(-/-) mice were protected against MT elevation in myocardial infarction-induced heart failure. Although both P2Y6 and P2Y2 receptors contributed to calcium mobilization, P2Y6 activation was mandatory for RhoA-GTP binding, myosin light chain, P42-P44, and c-Jun N-terminal kinase phosphorylation in arterial smooth muscle cells. In accordance with the opening of a nucleotide conduit in pressurized arteries, MT was altered by hemichannel pharmacological inhibitors and impaired in Cx43(+/-) and P2rx7(-/-) mesenteric resistance arteries. CONCLUSIONS: Signaling through P2 nucleotide receptors contributes to MT. This mechanism encompasses the release of nucleotides coupled to specific autocrine/paracrine activation of the uracil nucleotide P2Y6 receptor and may contribute to impaired tissue perfusion in cardiovascular diseases. PMID- 27255727 TI - CORR Insights(r): Proximal Tibia Reconstruction After Bone Tumor Resection: Are Survivorship and Outcomes of Endoprosthetic Replacement and Osteoarticular Allograft Similar? PMID- 27255728 TI - Pearls: How to Place an Interposition Segmental Bone Block for Lengthening or Alignment. PMID- 27255729 TI - Do the Reasons for Ceramic-on-ceramic Revisions Differ From Other Bearings in Total Hip Arthroplasty? AB - BACKGROUND: Despite widespread use of ceramic-on-ceramic (CoC) in total hip arthroplasty (THA) during the past 10 years, little is known about why revisions are performed in hips with this bearing or the time elapsed before revision. QUESTIONS/PURPOSES: The purposes of this study were: (1) Do the reasons for first revision differ between CoC bearings and other bearing couples? (2) Does the time to revision differ between CoC and other bearing couples? (3) Are there unique reasons for revisions of CoC bearings? METHODS: All members of the Societe Francaise de Chirurgie Orthopedique et Traumatologique (SoFCOT) who performed >= 30 revisions per year were invited to participate in this multicenter, prospective, observational study. Our data represent 12% of the revision procedures performed in France. A total of 2107 first revisions of THA (from January 2010 to December 2011) were done in 2107 patients (1201 females [57%] and 906 males [43%]; median age, 73 years; age range, 17-104 years) at the time of surgery after a median of 11 years (range, 0 day-42 years) after the primary THA. There were 238 of 2107 (11%) CoC, 148 of 2107 (7%) metal-on-metal (MoM), and 1721 of 2017 (82%) metal-on-polyethylene (MoP) bearings. RESULTS: The reasons for reoperation differed according to the bearing component: (1) for the MoP reference bearing (odds ratio [OR]; 95% confidence interval), cup loosening occurred in 698 of 1721 hips (41%), periprosthetic fracture in 220 of 1721 hips (13%), and osteolysis in 213 of 1721 hips (12%); (2) for CoC, cup loosening occurred in 41 of 238 hips (17%) (OR, 0.31 [0.22-0.43; p < 0.001), infection in 39 of 238 hips (16%) (OR, 1.63 [1.12-2.37]; p = 0.01), and dislocation in 23 of 238 hips (10%) (OR, 0.9 [0.57-1.42]; p = 0.9); (3) for MoM, cup loosening occurred in 28 of 148 hips (19%) (OR, 0.34 [0.22-0.52]; p < 0.001), adverse reaction to metallic debris in 26 of 148 hips (18%) (OR, 18.12 [9.84-33.4]; p < 0.001), and infection in 16 of 148 hips (11%) (OR, 1 [0.59-1.73]; p = 0.9). In comparison with MoP, osteolysis was rarely the reason for revision in CoC (four of 238 hips [2%]; OR, 0.12 [0.05-0.33]; p < 0.001), but this bearing was frequently revised because of iliopsoas irritation (18 of 238 hips [8%]; OR, 4.9 [2.7-9]; p < 0.001). The time elapsed before revision differed between bearings: median of 3 years (range, 3 days to 28 years) for CoC and 4 years (range, 14 days to 37 years) for MoM versus a median 13 years (range, 0 day to 42 years) for MoP (p < 0.001). Thirty-seven of the 238 revisions (16%) were directly related to ceramic use (ceramic breakage [n = 23], squeaking [n = 6], impingement [n = 7], incorrect ceramic insert insertion [n = 1]). No factors were identified that contributed to breakage of the 12 bulk ceramic components (eight heads, four inserts, four of 12 Delta ceramic). No factors were associated with squeaking, iliopsoas irritation, or impingement, but component orientation was not assessed. CONCLUSIONS: The reasons and time to first revision differed between CoC and other bearings. CoC THAs are revised earlier and are sensitive to mechanical problems such as impingement, squeaking, and ceramic rupture that did not disappear with introduction of Delta ceramics and large-diameter (>= 36 mm) bearings. CoC was rarely revised for osteolysis, but a high rate of iliopsoas irritation requires further investigation. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27255730 TI - Cholesterol is required for maintaining T-tubule integrity and intercellular connections at intercalated discs in cardiomyocytes. AB - BACKGROUNDS: Low serum cholesterol levels are associated with cardiac arrhythmias and poor prognosis in patients with chronic heart failure. However, the underlying mechanisms by which decreases in cholesterol content lead to cardiac dysfunction remain unclear. Multiple studies have implicated damage to cardiac transverse (T)-tubules as a key mediator of excitation-contraction (E-C) coupling dysfunction and heart failure. Since the T-tubule membrane system is enriched in cholesterol, we hypothesized that depletion of membrane cholesterol promotes T tubule remodeling and E-C coupling dysfunction. METHODS AND RESULTS: We first examined the impact of membrane cholesterol depletion on T-tubule architecture by treating isolated C57BL/6 murine cardiomyocytes with methyl-beta-cyclodextrin (MbetaCD). T-tubule structural integrity was progressively decreased by MbetaCD in a concentration- and time-dependent manner. Membrane cholesterol depletion also promoted a severe decrease in the amplitude of Ca(2+) transients and an increase in Ca(2+) release dyssynchrony as well as a significant increase in the frequency of spontaneous Ca(2+) sparks. Reintroduction of cholesterol restored T tubule integrity and partially restored Ca(2+) handling properties in acutely treated myocytes and slowed T-tubule deterioration in response to chronic MbetaCD exposure. Studies were extended to determine the impact of membrane cholesterol depletion on T-tubule structure in intact hearts. In addition to T-tubule remodeling, Langendorff perfusion of MbetaCD resulted in rapid and severe disruption of the intercellular connections between cardiomyocytes, in particular at intercalated disc regions in intact hearts. CONCLUSIONS: These data provide the first evidence that cholesterol plays a critical role in maintaining cardiac T-tubule structure as well as the integrity of intercalated discs. PMID- 27255731 TI - Prognostic factors in children undergoing salvage surgery for bladder/prostate rhabdomyosarcoma. AB - BACKGROUND: Prognostic factors have been studied in patients with rhabdomyosarcoma in general, but little is known about prognostic factors in the subgroup of patients with bladder/prostate rhabdomyosarcoma (BP-RMS) requiring salvage surgery after failure of chemotherapy +/- radiotherapy to achieve local control. We reviewed the 28-year Italian experience with BP-RMS requiring salvage surgery after failure of nonsurgical management indicated by evidence of disease persistence after chemotherapy +/- radiotherapy. Our hypothesis was that the same variables identified as prognostic factors in the general population with RMS could have prognostic value in this subgroup. METHOD: Between 1986 and 2014, 108 patients with a histological diagnosis of BP-RMS were registered into three consecutive protocols. Patients undergoing salvage surgery after failure of chemotherapy +/- radiotherapy and follow-up >5 years were considered for study. Variables related to the patient, to treatment, and to the surgical specimen were compared using the log-rank test in patients who achieved and failed to achieve 5 year progression-free survival (5-yr PFS). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated for significant variables. RESULTS: Of the 108 patients enrolled in the protocols, 33 (30.6%) underwent salvage surgery and 26 matched study criteria. Seventeen patients were disease-free after a median follow-up of 125 months (range 65.5-311.7 months), 5-yr PFS 65.4%. Nine events were registered after a median follow-up of 5.4 months (range 1.9-27.5 months). Among the variables assessed (Table), only an undifferentiated histology proved to be significantly associated with a poorer 5-yr PFS, whereas a tumor size above 5 cm in the removed specimen approached significance. The OR (95% CI) for failure of 5-yr PFS was 28 (2.4-326.8) and 8.3 (1.03-67.1), respectively. CONCLUSION: 5 yr PFS proved unrelated to excision margins of the surgical specimen, that is on whether there was evidence of microscopic residues left behind during surgery. These data suggest that the outcome is more influenced by the biological properties of the tumor. If small foci of differentiated cells are left behind, these probably do not compromise final prognosis. In our patients requiring salvage bladder-prostate surgery after failure of chemotherapy +/- radiotherapy, long-term progression-free survival seemed unrelated to patient/tumor characteristics at presentation and preoperative management. Regarding the characteristics of the removed specimen, instead, an undifferentiated tumor histology and a diameter of the removed tumor >5 cm negatively influenced prognosis, whereas the presence of positive excision margins did not. PMID- 27255733 TI - Maintenance of peripheral tolerance to islet antigens. AB - Reestablishment of immune tolerance to the insulin-producing beta cells is the desired goal for type 1 diabetes (T1D) treatment and prevention. Immune tolerance to multiple islet antigens is defective in individuals with T1D, but the mechanisms involved are multifaceted and may involve loss of thymic and peripheral tolerance. In this review we discuss our current understanding of the varied mechanisms by which peripheral tolerance to islet antigens is maintained in healthy individuals where genetic protection from T1D is present and how this fails in those with genetic susceptibility to disease. Novel findings in regards to expression of neo-islet antigens, non-classical regulatory cell subsets and the impact of specific genetic variants on tolerance induction are discussed. PMID- 27255732 TI - Using metabarcoding to reveal and quantify plant-pollinator interactions. AB - Given the ongoing decline of both pollinators and plants, it is crucial to implement effective methods to describe complex pollination networks across time and space in a comprehensive and high-throughput way. Here we tested if metabarcoding may circumvent the limits of conventional methodologies in detecting and quantifying plant-pollinator interactions. Metabarcoding experiments on pollen DNA mixtures described a positive relationship between the amounts of DNA from focal species and the number of trnL and ITS1 sequences yielded. The study of pollen loads of insects captured in plant communities revealed that as compared to the observation of visits, metabarcoding revealed 2.5 times more plant species involved in plant-pollinator interactions. We further observed a tight positive relationship between the pollen-carrying capacities of insect taxa and the number of trnL and ITS1 sequences. The number of visits received per plant species also positively correlated to the number of their ITS1 and trnL sequences in insect pollen loads. By revealing interactions hard to observe otherwise, metabarcoding significantly enlarges the spatiotemporal observation window of pollination interactions. By providing new qualitative and quantitative information, metabarcoding holds great promise for investigating diverse facets of interactions and will provide a new perception of pollination networks as a whole. PMID- 27255735 TI - Erratum: Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis. PMID- 27255734 TI - Predictors of slow progression to diabetes in children with multiple islet autoantibodies. AB - Although most children with multiple islet autoantibodies develop type 1 diabetes, rate of progression is highly variable. The goal of this study was to explore potential factors involved in rate of progression to diabetes in children with multiple islet autoantibodies. The Diabetes Autoimmunity Study in the Young (DAISY) has followed 118 children with multiple islet autoantibodies for progression to diabetes. After excluding 27 children currently diabetes-free but followed for <10 years, the study population was grouped into: rapid progressors (N = 39) who developed diabetes in <5 years; moderate progressors (N = 25), diagnosed with diabetes within 5-10 years; and slow progressors (N = 27), diabetes-free for >10 years. Islet autoimmunity appeared at 4.0 +/- 3.5, 3.2 +/- 1.8 and 5.8 +/- 3.1 years of age in rapid, moderate and slow progressors, respectively (p = 0.006). Insulin autoantibody levels were lower in slow progressors compared to moderate and rapid progressors. The groups did not differ by gender, ethnicity, family history, susceptibility HLA and non-HLA genes. The rate of development of individual islet autoantibodies including mIAA, GADA, IA 2A and ZnT8A were all slower in the slow versus moderate/rapid progressors. In multivariate analyses, older age at seroconversion and lower initial mIAA levels independently predicted slower progression to diabetes. Later onset of islet autoimmunity and lower autoantibody levels predicted slower progression to diabetes among children with multiple islet autoantibodies. These factors may need to be considered in the design of trials to prevent type 1 diabetes. PMID- 27255736 TI - Manipulating Google's Knowledge Graph Box to Counter Biased Information Processing During an Online Search on Vaccination: Application of a Technological Debiasing Strategy. AB - BACKGROUND: One of people's major motives for going online is the search for health-related information. Most consumers start their search with a general search engine but are unaware of the fact that its sorting and ranking criteria do not mirror information quality. This misconception can lead to distorted search outcomes, especially when the information processing is characterized by heuristic principles and resulting cognitive biases instead of a systematic elaboration. As vaccination opponents are vocal on the Web, the chance of encountering their non-evidence-based views on immunization is high. Therefore, biased information processing in this context can cause subsequent impaired judgment and decision making. A technological debiasing strategy could counter this by changing people's search environment. OBJECTIVE: This study aims at testing a technological debiasing strategy to reduce the negative effects of biased information processing when using a general search engine on people's vaccination-related knowledge and attitudes. This strategy is to manipulate the content of Google's knowledge graph box, which is integrated in the search interface and provides basic information about the search topic. METHODS: A full 3x2 factorial, posttest-only design was employed with availability of basic factual information (comprehensible vs hardly comprehensible vs not present) as the first factor and a warning message as the second factor of experimental manipulation. Outcome variables were the evaluation of the knowledge graph box, vaccination-related knowledge, as well as beliefs and attitudes toward vaccination, as represented by three latent variables emerged from an exploratory factor analysis. RESULTS: Two-way analysis of variance revealed a significant main effect of availability of basic information in the knowledge graph box on participants' vaccination knowledge scores (F2,273=4.86, P=.01), skepticism/fear of vaccination side effects (F2,273=3.5, P=.03), and perceived information quality (F2,273=3.73, P=.02). More specifically, respondents receiving comprehensible information appeared to be more knowledgeable, less skeptical of vaccination, and more critical of information quality compared to participants exposed to hardly comprehensible information. Although, there was no significant interaction effect between the availability of information and the presence of the warning, there was a dominant pattern in which the presence of the warning appeared to have a positive influence on the group receiving comprehensible information while the opposite was true for the groups exposed to hardly comprehensible information and no information at all. Participants evaluated the knowledge graph box as moderately to highly useful, with no significant differences among the experimental groups. CONCLUSION: Overall, the results suggest that comprehensible information in the knowledge graph box positively affects participants' vaccination-related knowledge and attitudes. A small change in the content retrieval procedure currently used by Google could already make a valuable difference in the pursuit of an unbiased online information search. Further research is needed to gain insights into the knowledge graph box's entire potential. PMID- 27255737 TI - Ultrasonically improved semi-hydrogenation of alkynes to (Z-)alkenes over novel lead-free Pd/Boehmite catalysts. AB - This paper reports the application of ultrasound in the semi-hydrogenation of alkynes over two novel Pd/Boehmite catalysts. The semi-hydrogenations of phenylacetylene, diphenylacetylene and 2-butyne-1,4-diol have either been investigated in an ultrasonic bath under atmospheric hydrogen pressure, or in an ultrasonic horn reactor under 0.1-0.5MPa hydrogen pressure. Alkyne hydrogenation was suppressed by sonication under atmospheric hydrogen pressure, but promoted by sonication under 0.1MPa of hydrogen pressure. Sonication increased selectivity towards the semi-hydrogenated products in both cases. Catalyst loading, hydrogen pressure, temperature and the presence of quinoline, all impacted on hydrogenation rate, activity and selectivity to semi-hydrogenated products. Palladium leaching from the catalyst was evaluated in ethanol and hexane both under plain stirring and sonication. PMID- 27255738 TI - Compositional data analysis of the microbiome: fundamentals, tools, and challenges. AB - PURPOSE: Human microbiome studies are within the realm of compositional data with the absolute abundances of microbes not recoverable from sequence data alone. In compositional data analysis, each sample consists of proportions of various organisms with a sum constrained to a constant. This simple feature can lead traditional statistical treatments when naively applied to produce errant results and spurious correlations. METHODS: We review the origins of compositionality in microbiome data, the theory and usage of compositional data analysis in this setting and some recent attempts at solutions to these problems. RESULTS: Microbiome sequence data sets are typically high dimensional, with the number of taxa much greater than the number of samples, and sparse as most taxa are only observed in a small number of samples. These features of microbiome sequence data interact with compositionality to produce additional challenges in analysis. CONCLUSIONS: Despite sophisticated approaches to statistical transformation, the analysis of compositional data may remain a partially intractable problem, limiting inference. We suggest that current research needs include better generation of simulated data and further study of how the severity of compositional effects changes when sampling microbial communities of widely differing diversity. PMID- 27255739 TI - Challenges for case-control studies with microbiome data. AB - PURPOSE: In case-control studies of the human microbiome, the goal is to evaluate whether cases differ from controls in the microbiome composition of a particular body habitat and which taxa are responsible for the differences. These studies leverage sequencing technology and spectroscopy that provide new measurements of the microbiome. METHODS: Three challenges in conducting reproducible microbiome research using a case-control design are compensating for differences in observed and actual microbial community composition, detecting "rare" taxa in microbial communities, and choosing properly powered analysis methods. The significance of each challenge, evaluation of commonly held views, analysis of unanswered questions, and suggestions of strategies for solutions are discussed. RESULTS: Understanding the effects of these choices on case-control analyses has been underappreciated, with an implicit assumption that further advances in technology will address all the current shortcomings. CONCLUSIONS: It is recommended that research on the human microbiome include positive and negative control experiments to provide insight into bias, contamination, and technical variation. Research protocols such as these may afford a better opportunity to make quantitative and qualitative adjustments to data, thereby reducing the risk of falsely positive results, increasing power to discover true disease determinants, and enhancing interpretation across studies. PMID- 27255740 TI - Predictors of mortality in pediatric trauma: experiences of a level 1 trauma center and an assessment of the International Classification Injury Severity Score (ICISS). AB - OBJECTIVES: Injury severity scoring tools allow systematic comparison of outcomes in trauma research and quality improvement by indexing an expected mortality risk for certain injuries. This study investigated the predictive value of the empirically derived ICD9-derived Injury Severity Score (ICISS) compared to expert consensus-derived scoring systems for trauma mortality in a pediatric population. METHODS: 1935 consecutive trauma patients aged <18 years from 1/2000 to 12/2012 were reviewed. Mechanism of injury (MOI), Injury Severity Score (ISS), Revised Trauma Score (RTS), Trauma Score ISS (TRISS), and ICISS were compared using univariate and multivariate logistic regression analysis and receiver operator characteristic analysis. RESULTS: The population was a median age of 11 +/- 6 year, 70 % male, and 76 % blunt injury. Median ISS 13 +/- 12 and overall mortality 3.5 %. Independent predictors of mortality were initial hematocrit [odds ratio (OR) 0.83 (0.73-0.95)], HCO3 [OR 0.82 (0.67-0.98)], Glasgow Coma Scale score [OR 0.75 (0.62-0.90)], and ISS [OR 1.10 (1.04-1.15)]. TRISS was superior to ICISS in predicting survival [area under receiver operator curve: 0.992 (0.982-1.000) vs 0.888 (0.838-0.938)]. CONCLUSIONS: ICISS was inferior to existing injury scoring tools at predicting mortality in pediatric trauma patients. PMID- 27255742 TI - Reimbursable drug classes and ceilings in Italy: why not only one? PMID- 27255741 TI - Notochordal cell conditioned medium (NCCM) regenerates end-stage human osteoarthritic articular chondrocytes and promotes a healthy phenotype. AB - BACKGROUND: Notochordal cell conditioned medium (NCCM) derived from non chondrodystrophic dogs has pro-anabolic and anti-catabolic effects upon nucleus pulposus (NP) cells. Here, for the first time, we assessed the ability of NCCM to influence the production of extracellular matrix and inflammatory proteins by healthy and osteoarthritic human chondrocytes within engineered cartilage tissues. We hypothesized that, similar to its action on NP cells, NCCM exerts metabolic and anti-catabolic effects on human articular chondrocytes and has the potential to significantly counteract inflammatory mediators. METHODS: Chondrocytes from nine non-osteoarthritic patients and from six osteoarthritic (OA) donors at the time of total knee arthroplasty were chondro-differentiated in pellets for 2 weeks. Non-OA pellets were exposed for 72 hours to IL-1beta/TNF alpha and then cultured up to 14 days in 2 % FBS-supplemented NCCM or 2 % FBS supplemented medium (control (ctr)). OA pellets were cultured in NCCM or ctr medium without pro-inflammatory treatment. Tissues after each culture phase were analyzed biochemically (GAG/DNA), (immuno-) histologically (collagen I, II and GAG) and by Western blotting. Supernatants were analyzed by ELISA. RESULTS: Response to NCCM was age and disease dependent with healthy chondrocyte pellets (from donors >55 years of age) recovering their glycosaminoglycan (GAG) contents to baseline levels only with NCCM. OA pellets treated with NCCM significantly increased GAG content (1.8-fold) and levels of hyaluronic acid link protein (HAPLN), fibromodulin and SOX-9. The catabolic proteins (matrix metalloproteinase (MMP)-3 and MMP-13) and pro-inflammatory enzyme levels (cyclooxygenase-2 (COX-2)) were markedly reduced and there was significantly reduced secretion of pro inflammatory chemokines (IL-6 and IL-8). CONCLUSIONS: NCCM restores cartilage matrix production of end-stage human OA chondrocytes towards a healthy phenotype and suppresses the production of inflammatory mediators. Harnessing the necessary and sufficient factors within NCCM that confers chondroprotection and regenerative effects could lead to a minimally invasive agent for treatment of degenerative and inflammatory joint diseases. PMID- 27255743 TI - Evaluation of knowledge-based reconstruction for magnetic resonance volumetry of the right ventricle after arterial switch operation for dextro-transposition of the great arteries. AB - Right ventricular (RV) volume and function evaluation is essential in the follow up of patients after arterial switch operation (ASO) for dextro-transposition of the great arteries (d-TGA). Cardiac magnetic resonance (CMR) imaging using the Simpson's method is the gold-standard for measuring these parameters. However, this method can be challenging and time-consuming, especially in congenital heart disease. Knowledge-based reconstruction (KBR) is an alternative method to derive volumes from CMR datasets. It is based on the identification of a finite number of anatomical RV landmarks in various planes, followed by computer-based reconstruction of the endocardial contours by matching these landmarks with a reference library of representative RV shapes. The purpose of this study was to evaluate the feasibility, accuracy, reproducibility and labor intensity of KBR for RV volumetry in patients after ASO for d-TGA. The CMR datasets of 17 children and adolescents (males 11, median age 15) were studied for RV volumetry using both KBR and Simpson's method. The intraobserver, interobserver and intermethod variabilities were assessed using Bland-Altman analyses. Good correlation between KBR and Simpson's method was noted. Intraobserver and interobserver variability for KBR showed excellent agreement. Volume and function assessment using KBR was faster when compared with the Simpson's method (5.1 +/- 0.6 vs. 6.7 +/- 0.9 min, p < 0.001). KBR is a feasible, accurate, reproducible and fast method for measuring RV volumes and function derived from CMR in patients after ASO for d TGA. PMID- 27255744 TI - Effect of household size on mental problems in children: results from the Norwegian Mother and Child Cohort study. AB - BACKGROUND: Most people in industrialized societies grow up in core (parents only) families with few if any siblings. Based on an evolutionary perspective, it may be argued that this environment reflects a mismatch, in that the tribal setting offered a larger number of close affiliates. The present project examined whether this mismatch may have a negative impact on mental health. METHODS: We used data from the Norwegian Mother and Child Cohort Study (MoBa), which includes 114 500 children. The mothers were recruited during pregnancy and followed up with questionnaires as the infants grew older. Correlates between number and type of people living in the household and questions probing mental health were corrected for likely confounders. RESULTS: The number of household members correlated with scores on good mental health at all ages tested (3, 5 and 8 years). The effects were distinct, highly significant, and present regardless of how mental issues were scored. The outcome could be attributed to having older siblings, rather than adults beyond parents. The more siblings, and the closer in age, the more pronounced was the effect. Living with a single mother did not make any difference compared to two parents. Girls were slightly more responsive to the presence of siblings than boys. Household pets did not have any appreciable impact. CONCLUSION: A large household is associated with fewer mental problems in children. PMID- 27255745 TI - Poorly Controlled Congenital Hypothyroidism due to an Underlying Allgrove Syndrome. AB - BACKGROUND: Congenital hypothyroidism of thyroidal origin (CHT) is a common disorder in pediatric endocrinology practices, which can be difficult to manage. Elevated thyrotropin (TSH) concentrations are in the great majority of cases explained by poor compliance to levothyroxine therapy. METHODS: Case description. RESULTS: We present a boy with CHT, with 2 heterozygous mutations in the TSH receptor gene, who showed persistently elevated TSH concentrations and psychomotor retardation, initially misinterpreted as malcompliance. At the age of 4 years, he was diagnosed with adrenal insufficiency, wherefore a broad diagnostic search was initiated. After the start of glucocorticoid replacement therapy, his TSH normalized and the levothyroxine could be lowered. At the age of 6 years, his TSH increased again, this time caused by malabsorption of levothyroxine due to esophageal achalasia. In retrospect, alacrima was also present and the diagnosis of Allgrove syndrome was genetically confirmed. The CHT was considered a separate disease entity. CONCLUSIONS: In case of persistently elevated TSH levels in children with CHT, causes other than noncompliance must be considered. Second, in establishing the cause of adrenal insufficiency, specific symptoms, such as alacrima, are easily overlooked. Third, Allgrove syndrome is a rare disorder, in which diagnostic delay can lead to potentially life-threatening complications. PMID- 27255746 TI - Complete sequence of a double-stranded RNA from the phytopathogenic fungus Erysiphe cichoracearum that might represent a novel endornavirus. AB - A double-stranded RNA (dsRNA) HBJZ1506 recovered from the phytopathogenic fungus Erysiphe cichoracearum infecting Calendula officinalis in Jingzhou, Hubei Province, China, was sequenced. HBJZ1506 comprises 11,908 nucleotides (nt) and contains a 11,859-nt-long open reading frame (ORF) coding for a polypeptide that is 61 % identical to that of a putative endornavirus named grapevine endophyte endornavirus (GeEV). The putative polyprotein has an RNA-dependent RNA polymerase (RdRp) domain and an RNA helicase domain, which show homology to and have an arrangement that is similar to that of their counterparts in approved or putative endornaviruses. In a phylogenetic tree constructed using amino acid sequences of the RdRp region of HBJZ1506 and selected endornaviruses, HBJZ1506 clustered with endornaviruses and formed a well-supported monophyletic branch with GeEV. These results suggest that HBJZ1506 might represent a novel endornavirus, for which the name Erysiphe cichoracearum endornavirus (EcEV) is proposed. PMID- 27255747 TI - Genetic relatedness of infectious hematopoietic necrosis virus (IHNV) from cultured salmonids in Korea. AB - Infectious hematopoietic necrosis virus (IHNV; n = 18) was identified in the Korean national surveillance program between February 2013 and April 2015, suggesting that IHNV is a major viral pathogen in cultured salmonids. By phylogeny analysis, we found that the JRt-Nagano and JRt-Shizuoka groups could each be further subdivided into three distinct subtypes. The Korean strains were genetically similar to Japanese isolates, suggesting introduction from Japan. Interestingly, the amino acid sequences of the middle glycoprotein gene show that distinct Korean subtypes have circulated, indicating that the settled IHNVs might be evolved stably in cultured salmonid farm environments. PMID- 27255748 TI - Influenza virus neuraminidase (NA): a target for antivirals and vaccines. AB - Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage. PMID- 27255749 TI - BMI Trajectories as a Harbinger of Pre-Diabetes or Underdiagnosed Diabetes: an 18 Year Retrospective Cohort Study in Taiwan. AB - BACKGROUND: Although prior studies have examined BMI trajectories in Western populations, little is known regarding how BMI trajectories in Asian populations vary between adults with and without diabetes. OBJECTIVE: To examine how BMI trajectories vary between those developing and not developing diabetes over 18 years in an Asian cohort. DESIGN: Multilevel modeling was used to depict levels and rates of change in BMI for up to 18 years for participants with and without self-reported physician-diagnosed diabetes. PARTICIPANTS: We used 14,490 data points available from repeated measurements of 3776 participants aged 50+ at baseline without diabetes from a nationally representative survey of the Taiwan Longitudinal Study on Aging (TLSA1989-2007). MAIN MEASURES: We defined development of diabetes as participants who first reported diabetes diagnoses in 2007 but had no diabetes diagnoses at baseline. We defined the reference group as those participants who reported the absence of diabetes at baseline and during the entire follow-up period. KEY RESULTS: When adjusted for time-varying comorbidities and behavioral factors, higher level and constant increases in BMI were present more than 6.5 years before self-reported diabetes diagnosis. The higher BMI level associating with the development of diabetes was especially evident in females. Within 6.5 years prior to self-reported diagnosis, however, a wider range of decreases in BMI occurred (betadiabetes = 1.294, P = 0.0064; betadiabetes*time = 0.150, P = 0.0327; betadiabetes*time (2) = -0.008, P = 0.0065). The faster rate of increases in BMI followed by a greater decline was especially prominent in males and individuals with BMI ?24. CONCLUSIONS: An unintentional decrease in BMI in sharp contrast to the gradually rising BMI preceding that time may be an alarm for undiagnosed diabetes or a precursor to developing diabetes. PMID- 27255750 TI - An Electronic Adherence Measurement Intervention to Reduce Clinical Inertia in the Treatment of Uncontrolled Hypertension: The MATCH Cluster Randomized Clinical Trial. AB - BACKGROUND: To appropriately manage uncontrolled hypertension, clinicians must decide whether blood pressure (BP) is above goal due to a need for additional medication or to medication nonadherence. Yet, clinicians are poor judges of adherence, and uncertainty about adherence may promote inertia with respect to medication modification. OBJECTIVE: We aimed to determine the effect of sharing electronically-measured adherence data with clinicians on the management of uncontrolled hypertension. DESIGN: This was a cluster randomized trial. PARTICIPANTS: Twenty-four primary care providers (12 intervention, 12 usual care; cluster units) and 100 patients with uncontrolled hypertension (65 intervention, 35 usual care) were included in the study. INTERVENTIONS: At one visit per patient, clinicians in the intervention group received a report summarizing electronically measured adherence to the BP regimen and recommended clinical actions. Clinicians in the control group did not receive a report. MAIN MEASURES: The primary outcome was the proportion of visits with appropriate clinical management (i.e., treatment intensification among adherent patients and adherence counseling among nonadherent patients). Secondary outcomes included patient-rated quality of care and communication during the visit. KEY RESULTS: The proportion of visits with appropriate clinical management was higher in the intervention group than the control group (45 out of 65; 69 %) versus (12 out of 35; 34 %; p = 0.001). A higher proportion of adherent patients in the intervention group had their regimen intensified (p = 0.01), and a higher proportion of nonadherent patients in the intervention group received adherence counseling (p = 0.005). Patients in the intervention group were more likely to give their clinician high ratings on quality of care (p = 0.05), and on measures of patient-centered (p = 0.001) and collaborative communication (p = 0.02). CONCLUSIONS: Providing clinicians with electronically-measured antihypertensive adherence reports reduces inertia in the management of uncontrolled hypertension. TRIAL REGISTRATION: NCT01257347 ; http://clinicaltrials.gov/show/ NCT01257347. PMID- 27255753 TI - Pregnant women in Scotland to be offered free vitamins. PMID- 27255751 TI - Sub-synaptic localization of Cav3.1 T-type calcium channels in the thalamus of normal and parkinsonian monkeys. AB - T-type calcium channels (Cav3) are key mediators of thalamic bursting activity, but also regulate single cells excitability, dendritic integration, synaptic strength and transmitter release. These functions are strongly influenced by the subcellular and subsynaptic localization of Cav3 channels along the somatodendritic domain of thalamic cells. In Parkinson's disease, T-type calcium channels dysfunction in the basal ganglia-receiving thalamic nuclei likely contributes to pathological thalamic bursting activity. In this study, we analyzed the cellular, subcellular, and subsynaptic localization of the Cav3.1 channel in the ventral anterior (VA) and centromedian/parafascicular (CM/Pf) thalamic nuclei, the main thalamic targets of basal ganglia output, in normal and parkinsonian monkeys. All thalamic nuclei displayed strong Cav3.1 neuropil immunoreactivity, although the intensity of immunolabeling in CM/Pf was significantly lower than in VA. Ultrastructurally, 70-80 % of the Cav3.1 immunoreactive structures were dendritic shafts. Using immunogold labeling, Cav3.1 was commonly found perisynaptic to asymmetric and symmetric axo-dendritic synapses, suggesting a role of Cav3.1 in regulating excitatory and inhibitory neurotransmission. Significant labeling was also found at non-synaptic sites along the plasma membrane of thalamic neurons. There was no difference in the overall pattern and intensity of immunostaining between normal and parkinsonian monkeys, suggesting that the increased rebound bursting in the parkinsonian state is not driven by changes in Cav3.1 expression. Thus, T-type calcium channels are located to subserve neuronal bursting, but also regulate glutamatergic and non glutamatergic transmission along the whole somatodendritic domain of basal ganglia-receiving neurons of the primate thalamus. PMID- 27255752 TI - A novel recombinant 6Abeta15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 * Tg-AD mice. AB - Alzheimer's disease (AD) is a neurodegenerative disorder that impairs memory and cognition. Targeting amyloid-beta (Abeta) may be currently the most promising immunotherapeutic strategy for AD. In this study, a recombinant chimeric 6Abeta15 THc-C immunogen was formulated with alum adjuvant as a novel Abeta B-cell epitope candidate vaccine (rCV02) for AD. We examined its efficacy in preventing the cognitive deficit and synaptic impairment in 3 * Tg-AD mice. Using a toxin derived carrier protein, the rCV02 vaccine elicited robust Abeta-specific antibodies that markedly reduced AD-like pathology and improved behavioral performance in 3 * Tg-AD mice. Along with the behavioral improvement in aged 3 * Tg-AD mice, rCV02 significantly decreased calpain activation concurrent with reduced soluble Abeta or oligomeric forms of Abeta, probably by preventing dynamin 1 and PSD-95 degradation. Our data support the hypothesis that reducing Abeta levels in rCV02-immunized AD mice increases the levels of presynaptic dynamin 1 and postsynaptic PSD-95 allowing functional recovery of cognition. In conclusion, this novel and highly immunogenic rCV02 shows promise as a new candidate prophylactic vaccine for AD and may be useful for generating rapid and strong Abeta-specific antibodies in AD patients with pre-existing memory Th cells generated after immunization with conventional tetanus toxoid vaccine. PMID- 27255754 TI - RNA-binding protein CUGBP1 regulates insulin secretion via activation of phosphodiesterase 3B in mice. AB - AIMS/HYPOTHESIS: CUG-binding protein 1 (CUGBP1) is a multifunctional RNA-binding protein that regulates RNA processing at several stages including translation, deadenylation and alternative splicing, as well as RNA stability. Recent studies indicate that CUGBP1 may play a role in metabolic disorders. Our objective was to examine its role in endocrine pancreas function through gain- and loss-of function experiments and to further decipher the underlying molecular mechanisms. METHODS: A mouse model in which type 2 diabetes was induced by a high-fat diet (HFD; 60% energy from fat) and mice on a standard chow diet (10% energy from fat) were compared. Pancreas-specific CUGBP1 overexpression and knockdown mice were generated. Different lengths of the phosphodiesterase subtype 3B (PDE3B) 3' untranslated region (UTR) were cloned for luciferase reporter analysis. Purified CUGBP1 protein was used for gel shift experiments. RESULTS: CUGBP1 is present in rodent islets and in beta cell lines; it is overexpressed in the islets of diabetic mice. Compared with control mice, the plasma insulin level after a glucose load was significantly lower and glucose clearance was greatly delayed in mice with pancreas-specific CUGBP1 overexpression; the opposite results were obtained upon pancreas-specific CUGBP1 knockdown. Glucose- and glucagon-like peptide1 (GLP-1)-stimulated insulin secretion was significantly attenuated in mouse islets upon CUGBP1 overexpression. This was associated with a strong decrease in intracellular cAMP levels, pointing to a potential role for cAMP PDEs. CUGBP1 overexpression had no effect on the mRNA levels of PDE1A, 1C, 2A, 3A, 4A, 4B, 4D, 7A and 8B subtypes, but resulted in increased PDE3B expression. CUGBP1 was found to directly bind to a specific ATTTGTT sequence residing in the 3' UTR of PDE3B and stabilised PDE3B mRNA. In the presence of the PDE3 inhibitor cilostamide, glucose- and GLP-1-stimulated insulin secretion was no longer reduced by CUGBP1 overexpression. Similar to CUGBP1, PDE3B was overexpressed in the islets of diabetic mice. CONCLUSIONS/INTERPRETATION: We conclude that CUGBP1 is a critical regulator of insulin secretion via activating PDE3B. Repressing this protein might provide a potential strategy for treating type 2 diabetes. PMID- 27255756 TI - Corrigendum. AB - Maltais, F., Singh, S., Donald, A., Crater, G., Church, A., Goh, A. et al. (2014) Effects of a combination of umeclidinium/vilanterol on exercise endurance in patients with chronic obstructive pulmonary disease: two randomized, double-blind clinical trials. Ther Adv Respir Dis 8: 169-181. PMID- 27255755 TI - The Respiratory Protection Effectiveness Clinical Trial (ResPECT): a cluster randomized comparison of respirator and medical mask effectiveness against respiratory infections in healthcare personnel. AB - BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts. METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team. DISCUSSION: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010). PMID- 27255757 TI - Utilisation and Tolerability of Aliskiren in the Primary Care Setting in England. AB - Aliskiren (Rasilez), a direct renin inhibitor, is indicated for the treatment of essential hypertension. A postmarketing prescription-event monitoring (PEM) study was conducted in England to monitor the safety and utilization of aliskiren. Summary statistics and event incidence densities were calculated. The cohort consisted of 6385 individuals with a median age of 68 years (interquartile range, 59-76). Aliskiren was largely prescribed for its licensed indication of hypertension (93.3%) and was reported as "effective" by the prescriber in 77.4% of individuals. Frequently reported clinical events during treatment were diarrhea (3.1% of on-treatment events), malaise/lassitude (3.0%), and nausea/vomiting (1.2%), which were also common reasons for treatment cessation. Renal events were rare, with 24 cases probably or possibly related to aliskiren use, and four of which were classified as acute renal failure using RIFLE (Risk Injury Failure Loss End-Stage Kidney Disease) criteria. These results should be used in conjunction with other clinical and pharmacoepidemiologic studies to optimize the safe prescribing of aliskiren. PMID- 27255758 TI - Direct quantification of rare earth doped titania nanoparticles in individual human cells. AB - There are many possible biomedical applications for titania nanoparticles (NPs) doped with rare earth elements (REEs), from dose enhancement and diagnostic imaging in radiotherapy, to biosensing. However, there are concerns that the NPs could disintegrate in the body thus releasing toxic REE ions to undesired locations. As a first step, we investigate how accurately the Ti/REE ratio from the NPs can be measured inside human cells. A quantitative analysis of whole, unsectioned, individual human cells was performed using proton microprobe elemental microscopy. This method is unique in being able to quantitatively analyse all the elements in an unsectioned individual cell with micron resolution, while also scanning large fields of view. We compared the Ti/REE signal inside cells to NPs that were outside the cells, non-specifically absorbed onto the polypropylene substrate. We show that the REE signal in individual cells co-localises with the titanium signal, indicating that the NPs have remained intact. Within the uncertainty of the measurement, there is no difference between the Ti/REE ratio inside and outside the cells. Interestingly, we also show that there is considerable variation in the uptake of the NPs from cell-to-cell, by a factor of more than 10. We conclude that the NPs enter the cells and remain intact. The large heterogeneity in NP concentrations from cell-to-cell should be considered if they are to be used therapeutically. PMID- 27255759 TI - The Parasol Protocol for computational mutagenesis. AB - To aid in the discovery and development of peptides and proteins as therapeutic agents, a virtual screen can be used to predict trends and direct workflow. We have developed the Parasol Protocol, a dynamic method implemented using the AMBER MD package, for computational site-directed mutagenesis. This tool can mutate between any pair of amino acids in a computationally expedient, automated manner. To demonstrate the potential of this methodology, we have employed the protocol to investigate a test case involving stapled peptides, and have demonstrated good agreement with experiment. PMID- 27255760 TI - Hepatitis B virus whole-X and X protein play distinct roles in HBV-related hepatocellular carcinoma progression. AB - BACKGROUND: The role of HBV X protein (HBx) in the development of hepatocellular carcinoma (HCC) has been well studied. However, little is known about the molecular functions of HBV whole-X protein (HBwx), a protein fused with HBx and upstream 56 amino acid, in HCC. In current study, the molecular functions of HBwx in HCC pathogenesis has been investigated, as well as comparison between HBwx and HBx. METHODS: Expression of HBwx and HBx in 50 HCC tissues was examined by immunohistochemistry. Their tumor-forming abilities were evaluated by an animal model and colony formation assay. Migration and invasion were detected by transwell assay and subcellular localization was tracked by GFP fluorescence. Cell proliferation, cell cycle and apoptosis were detected by CCK8 and FCM. Protein level was determined by Western blotting. RESULTS: HBwx was present in 72 % (36/50) of the liver tumor tissues and mainly expressed in the nucleus and deposited in the cytoplasm surrounding karyotheca. HBwx showed a promoting effect on tumorigenesis and growth in vivo and in vitro as well as cell migration and invasion, whilst such effect is compromised compared with that of HBx. Further analysis demonstrated differences in cell proliferation, cell cycle and cell apoptosis between cells expressing HBwx and those expressing HBx. Additionally, it was confirmed that RKIP-p-ERK pathway was involved in HBwx-related tumor formation. CONCLUSION: HBwx, with the extra 56 amino acids, is closely related with hepatocarcinogenesis, while displays different biological functions from HBx. PMID- 27255761 TI - Exploiting E. coli auxotrophs for leucine, valine, and threonine specific methyl labeling of large proteins for NMR applications. AB - A simple and cost effective method to independently and stereo-specifically incorporate [(1)H,(13)C]-methyls in Leu and Val in proteins is presented. Recombinant proteins for NMR studies are produced using a tailored set of auxotrophic E. coli strains. NMR active isotopes are routed to either Leu or Val methyl groups from the commercially available and scrambling-free precursors alpha-ketoisovalerate and acetolactate. The engineered strains produce deuterated proteins with stereospecific [(1)H,(13)C]-methyl labeling separately at Leu or Val amino acids. This is the first method that achieves Leu-specific stereospecific [(1)H,(13)C]-methyl labeling of proteins and scramble-free Val specific labeling. Use of auxotrophs drastically decreases the amount of labeled precursor required for expression without impacting the yield. The concept is extended to Thr methyl labeling by means of a Thr-specific auxotroph that provides enhanced efficiency for use with the costly L-[4-(13)C,2,3-(2)H2,(15)N] Thr reagent. The Thr-specific strain allows for the production of Thr [(13)CH3](gamma2) labeled protein with an optimal isotope incorporation using up to 50 % less labeled Thr than the traditional E. coli strain without the need for (2)H-glycine to prevent scrambling. PMID- 27255762 TI - Aureimonas galii sp. nov. and Aureimonas pseudogalii sp. nov. isolated from the phyllosphere of Galium album. AB - Four yellow-pigmented, Gram-stain-negative, rod-shaped bacteria, strains PP-WC-4G 234T, PP-CE-2G-454T, PP-WC-1G-202 and PP-CC-3G-650, were isolated from the phyllosphere of Galium album. The strains shared 99.7-100 % 16S rRNA gene sequence similarity but could be differentiated by genomic fingerprinting using rep- and random amplification of polymorphic DNA PCRs. Phylogenetic analysis based on the 16S rRNA gene placed the strains within the family Aurantimonadaceae with highest 16S rRNA gene sequence similarity of 97.2-97.3 % to the type strain of Aureimonas phyllosphaerae. Sequence similarities to all other Aurantimonadaceae were below 97 %. The main cellular fatty acids of the strains were C18 : 1omega7c as the predominant fatty acid followed by C16 : 0 and summed feature 3 (C16 : 1omega7c/C16 : 1omega8c). The polyamine patterns of strains PP WC-4G-234T and PP-CE-2G-454T contained sym-homospermidine as a major compound, and the major respiratory quinone was ubiquinone Q-10. Predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, phosphatidylcholine, sulfoquinovosyldiacylglycerol, three unidentified phospholipids and one unidentified lipid only detectable after total lipid staining. The DNA G+C content was 66.4, 68.9, 67.4 and 70.5 mol% for strains PP-WC-4G-234T, PP-CE-2G 454T, PP-WC-1G-202 and PP-CC-3G-650, respectively. Based on phylogenetic, chemotaxonomic and phenotypic analyses we propose two novel species of the genus Aureimonas, Aureimonas galii sp. nov. with PP-WC-4G-234T (=LMG 28655T=CIP 110892T) as the type strain and Aureimonas pseudogalii sp. nov. with PP-CE-2G 454T (=LMG 29411T=CCM 8665T) as the type strain and two further strains representing the same species, PP-WC-1G-202 and PP-CC-3G-650. PMID- 27255764 TI - Contributions of Dryland Forest (Caatinga) to Species Composition, Richness and Diversity of Drosophilidae. AB - In this study, semi-arid environments were tested to see if they support insect diversity. This was evaluated through the structure of the composition of assemblies of drosophilids in three conservation units placed in three different ecoregions in the dryland forests, Caatinga. This is a unique biome in northeast Brazil, comprising approximately 10% of the country. Species richness was investigated over 2 years during a prolonged drought, considered the worst affliction the Caatinga ecosystem had experienced in the last 50 years. Alpha diversity indices and the ecological similarity between the samples were calculated to determine how the environments drive the composition of Drosophilidae in such semi-arid places. A total of 7352 specimens were sampled. They were classified into 20 species belonging to four genera: Drosophila, Rhinoleucophenga, Scaptodrosophila, and Zaprionus. Drosophila nebulosa Sturtevant (44.5%) and Drosophila cardini Sturtevant (12.5%) were the most abundant species. The occurrences and abundances of all the species differed greatly between sites. These results and other ecological analyses indicate that although placed in the same biome, there are great variability in the drosophilid species and abundance among the three protected and conserved dryland environments. PMID- 27255763 TI - Substantial Effects of Luseogliflozin Revealed by Analyzing Responses to Postprandial Hyperglycemia: Post Hoc Subanalyses of a Randomized Controlled Study. AB - INTRODUCTION: In our previous study investigating effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, on 24-h glycemic variability by continuous glucose monitoring (CGM), luseogliflozin elicited parallel downward shifts in fasting and postprandial glucose levels. However, further review of individual patients' data revealed that postprandial hyperglycemia was not reduced in some patients, while preprandial glucose was ameliorated in most patients. Therefore, we divided patients into two groups according to their postprandial glucose responses and conducted a post hoc subanalyses to elucidate which factors contributed to the differential effects of luseogliflozin. METHODS: Thirty-four Japanese type 2 diabetic patients in our previous randomized, double blind, placebo-controlled, crossover study with 7-day luseogliflozin administration were divided into postprandial glucose responders (PGR, n = 23, ameliorated peak glucose) and postprandial glucose non-responders (PGNR; n = 11, non-ameliorated peak glucose). Baseline characteristics, variations in CGM measured 24-h glucose levels, and other pharmacodynamic variabilities were compared. RESULTS: Baseline characteristics did not differ significantly between groups. Placebo-subtracted peak glucose was significantly lowered in PGR and significantly increased in PGNR (-43.8 and 17.9 mg/dL; both p < 0.05). Luseogliflozin significantly lowered "lowest glucose" (defined as the lowest level measured throughout a 24-h period) similarly in PGR and PGNR (-19.2 and 24.0 mg/dL; both p < 0.05), significantly reduced the mean amplitude of glucose excursions in PGR (-15.50 mg/dL; p < 0.05), and increased the area under the curve for plasma glucagon over 24 h in PGNR (median difference vs. placebo: 240 pg/mL h; p < 0.05). Luseogliflozin increased urinary glucose excretion (UGE) and decreased serum insulin by similar magnitudes in both groups. CONCLUSIONS: Luseogliflozin diminished glucose fluctuations in most patients by lowering peak glucose to a greater extent than lowest glucose. Luseogliflozin may also lower lowest glucose in patients whose peak glucose was not ameliorated despite increasing UGE. The glucagon increase in PGNR might explain its hypoglycemic effect on postprandial glucose. FUNDING: Taisho Pharmaceutical Co., Ltd, Tokyo, Japan. TRIAL REGISTRATION: JapicCTI-142548. PMID- 27255765 TI - Immature Stages of Six Species of Adelpha Hubner (Lepidoptera: Nymphalidae: Limenitidinae) from Southern Brazil Coastal Forests. AB - Six species of Adelpha Hubner from Balneario Barra do Sul (Santa Catarina) and Morretes (Parana) were collected as eggs or larvae and reared in captivity, aiming to provide descriptions and photography of the immature stages and imagoes. The species studied were Adelpha radiata radiata Fruhstorfer; Adelpha serpa serpa (Boisduval); Adelpha plesaure plesaure Hubner; Adelpha thesprotia (C. Felder & R. Felder); Adelpha lycorias lycorias (Godart); and Adelpha capucinus velia (C. Felder & R. Felder). Two new records of host plants were provided, Tapirira guianensis Aubl. for A. radiata radiata and Heteropterys for A. capucinus velia. This study provides a summary of host plants and the seasonality of occurrence of immature stages of these species. Data were organized in photographic plates that could be useful for the identification process. PMID- 27255766 TI - Fitness Advantage in Heterozygous Ladybird Beetle Eriopis connexa (Germar) Resistant to Lambda-Cyhalothrin. AB - The pyrethroid lambda-cyhalothrin is widely recommended for use against defoliators in crop ecosystems, but this broad-spectrum insecticide lacks efficacy against aphids; thus, key aphid predators such as the ladybird beetle Eriopis connexa (Germar) (Coleoptera: Coccinellidae) must be preserved. Given that populations of E. connexa recently identified as resistant to lambda cyhalothrin show potential of integrating chemical and biological control in crop ecosystems, a historical goal of integrated pest management. In the present study, the resistance maintenance over F1, F2, and F3 progenies from crossing resistant (R) and susceptible (S) E. connexa populations that might be expected after releasing R predator in the crop field and the F1 offspring performance when the R population is crossed with the S population are evaluated. The offspring performance is determined for F1 progenies from crossing the R population at F40- and F45-reared generations in the laboratory with the S population at F38- and F1-reared generations in the laboratory. The mortality rate in the heterozygous F1 progeny is low and similar to the rate for the R population (<5%), but it is about 75% in F2 and F3 progenies from crossing R and S populations. Fecundity and longevity of the heterozygous F1 progeny are significantly greater compared to the R population. These results suggest that when R population beetles are released and mating with S population residents, their field offspring retains the resistance phenotype with the advantages of greater egg production and longer survival compared to the parental R population. PMID- 27255767 TI - Toxicity of Piper aduncum (Piperaceae) Essential Oil Against Euschistus heros (F.) (Hemiptera: Pentatomidae) and Non-Effect on Egg Parasitoids. AB - Plant essential oils have been recognized as significant natural resources for insecticides. Herein, we have assessed the toxicity of the essential oil of Piper aduncum (Piperaceae) against Euschistus heros (F.) (Hemiptera: Pentatomidae), a key soybean pest in Neotropical America. In addition, we have assessed its effect on the performance of egg parasitoids. The essential oil was obtained from the leaves of P. aduncum via hydrodistillation. Subsequently, bioassays of the concentration response to eggs (contact and immersion methods), nymphs, and adults (topical application) were conducted, to assess the lethal effects on the stink bug. We also evaluated the performance of parasitism and adult emergence of egg parasitoids, when the host eggs were treated with essential oil. In the egg bioassay, both exposure methods were efficient for unviable eggs (immersion LC50 = 15.64 mg mL-1; contact LC50 = 21.29 mg mL-1), with the highlight on the immersion method. The bioassay with nymphs indicated a higher toxicity of essential oil, with lower concentrations (LC50 = 11.37 mg mL-1) being required to cause the death of insects. For adults, a reduction in survival of insects was observed, and consequently, there was a reduction in the number of individuals in the next generation. Although the essential oil was toxic to E. heros, it exhibited lower toxicity for egg parasitoids, as there was no effect on parasitism and the emergence of wasps. We discuss likely explanations for such selectivity. In summary, we found that the essential oil was promising for the control of E. heros, because it caused deleterious effects at all development stages of the stink bug and had no effect on parasitism and emergence of the egg parasitoids, which suggested compatibility with biological control. PMID- 27255768 TI - Constancy, Distribution, and Frequency of Lepidoptera Defoliators of Eucalyptus grandis and Eucalyptus urophylla (Myrtaceae) in Four Brazilian Regions. AB - The growth of the Brazilian forest sector with monocultures favors the adaptation of Arthropoda pests. The Lepidoptera order includes major pests of Eucalyptus spp. (Myrtaceae). The aim of this work is to study the population constancy, distribution, and frequency of Lepidoptera primary pests of Eucalyptus spp. Lepidoptera pests in Eucalyptus spp. plantations were collected in Tres Marias and Guanhaes (state of Minas Gerais), Niquelandia (state of Goias), and Monte Dourado (state of Para), Brazil, for a period of 5 years, with light traps and captures, every 15 days, for every region. The number of primary pest species (12) has been similar in the four regions, and even with 1.5 to 2.4% of the total species collected, this group has shown a high frequency, especially in Tres Marias, Niquelandia, and Monte Dourado, with 66.3, 54.2, and 40.0% of the individuals collected, respectively, for 5 years. The primary pest species have been constant and frequent in all the regions, with population peaks from February to September in Tres Marias, February and May in Niquelandia, and from July to September in Monte Dourado. The highest population peaks of these species have been recorded when the Eucalyptus spp. plants are 3 to 6 years old. The Guanhaes region is more stable and, therefore, has a lower possibility of outbreaks of the Lepidoptera primary pest species. PMID- 27255769 TI - Engaging Australian Aboriginal narratives to challenge attitudes and create empathy in health care: a methodological perspective. AB - BACKGROUND: Unconscious bias and negative attitudes towards minority groups have detrimental effects on the way health care is, or is not, provided to these groups. Recognition of racist attitudes and behaviours as well as understanding clients' experiences of health and health care are pivotal to developing better health care strategies to positively impact on the quality and safety of care provided to Indigenous people. Indigenous research demands inclusive research processes and the use of culturally appropriate methodologies. This paper presents a methodological account of collecting narratives which accurately and respectfully reflect Aboriginal Australians' experiences with health care in Western Australia. The purpose of these narratives is to provide health students and professionals with an opportunity to 'walk-in the shoes' of Aboriginal people where face-to-face interaction is not feasible. METHODS: With the incorporation of Indigenous peoples' voices being an important link in cultural safety, the project was led by an Indigenous Reference group, who encouraged active participation of Aboriginal people in all areas of the project. Using a phenomenological approach and guided by the Indigenous Reference group, yarning data collection was implemented to collect stories focusing on Aboriginal people's experiences with health care services. An open-access, on-line website was established to host education resources developed from these "yarns". RESULTS: Yarning provided a rich source of information on personal experiences and encouraged the story provider to recognise their facilitative role in the research process. While the methodology used in this project was lengthy and labour-intensive it afforded a respectful manner for story collection and highlighted several innate flaws when Western methods are applied to an Indigenous context. CONCLUSION: Engagement of an Indigenous Reference Group was pivotal to designing an appropriate methodology that incorporated the voices of Aboriginal people in a multimedia resource of Aboriginal narratives. However further research is warranted to understand how the resources are being used and integrated into curricula, and their impact on students and health care outcomes. PMID- 27255770 TI - Borderline personality disorder and violence in the UK population: categorical and dimensional trait assessment. AB - BACKGROUND: Borderline personality disorder (BPD) is characterised by difficulties with impulse control and affective dysregulation. It is unclear whether BPD contributes to the perpetration of violence or whether this is explained by comorbidity. We explored independent associations between categorical and dimensional representations of BPD and violence in the general population, and differential associations from individual BPD criteria. METHODS: We used a representative combined sample of 14,753 men and women from two British national surveys of adults (>=16 years). BPD was assessed using the Structured Clinical Interview II- Questionnaire. We measured self-reported violent behaviour in the past 5 years, including severity, victims and locations of incidents. Associations for binary, dimensional and trait-level exposures were performed using weighted logistic regression, adjusted for demography and comorbid psychopathology. RESULTS: Categorical diagnosis of BPD was associated only with intimate partner violence (IPV). Associations with serious violence leading to injuries and repetitive violence were better explained by comorbid substance misuse, anxiety and antisocial personality disorder (ASPD). However, anger and impulsivity BPD items were independently associated with most violent outcomes including severity, repetition and injury; suicidal behaviours and affective instability were not associated with violence. Both trait-level and severity dimensional analyses showed that BPD symptoms might impact males and females differently in terms of violence. CONCLUSIONS: For individuals diagnosed BPD, violence is better explained by comorbidity. However, BPD individual traits show different pathways to violence at the population level. Gender differences in BPD traits and their severity indicate distinct, underlying mechanisms towards violence. BPD and traits should be evaluated in perpetrators of IPV. PMID- 27255771 TI - New definition of sepsis and septic shock: What does it give us? PMID- 27255772 TI - Factors affecting surgery decision-making in patients with a chronic neurovascular condition. AB - AIMS AND OBJECTIVES: To explore the factors that affect patient decision-making for an elective surgery. BACKGROUND: Cerebral cavernous malformations are lesions found in the brain and spinal cord comprised of abnormal blood vessels, which bleed sporadically causing serious neurological deficits. Course of treatment for cerebral cavernous malformation is often ultimately left up to the patient, and can include symptom management or surgery. Decision-making for surgery in life threatening conditions has been well documented in the literature. Less extensive research has focused on elective surgeries, where patients have a choice. There has been no research on the factors that affect decision-making for cavernous malformation patients. DESIGN: Correlational self-report survey. METHODS: In part of a larger online study, participants were asked to rate the importance of six factors on their decision-making about surgery for cavernous malformation. RESULTS: Factors that were rated most important for individuals' decision-making included doctor's opinion regarding surgery, presence of disabling symptoms, fear of symptoms getting worse or developing new symptoms, and availability of an expert surgeon. Results indicated that these were rated as more important than having social support during recovery or having the means to pay for surgery. Additionally, having social support during recovery was rated as significantly more important than having the means to pay for surgery. CONCLUSIONS: Factors that affect decision-making for patients diagnosed with cavernous malformation were similar to those found with other medical conditions requiring elective surgery. This study will assist healthcare workers in understanding the decision making process of individuals who may choose an elective surgery for potentially disabling conditions with uncertain outcomes. RELEVANCE TO CLINICAL PRACTICE: Understanding the complex factors that affect decision-making in cavernous malformation will assist healthcare professionals to better communicate and support patients in their elective surgery decision-making. PMID- 27255773 TI - How Well Can Analytic Hierarchy Process be Used to Elicit Individual Preferences? Insights from a Survey in Patients Suffering from Age-Related Macular Degeneration. AB - BACKGROUND: In this study, we tested the feasibility of an interviewer-assisted analytic hierarchy process (AHP) in a special patient population with age-related macular degeneration (AMD). OBJECTIVES: One aim was to generate preference weights regarding AMD treatment characteristics. A secondary aim was to explore the consistency of preference judgments and reasons for inconsistency. METHODS: We generated quantitative importance weights for decision criteria using the matrix multiplication method. A qualitative study component in the form of asking patients to think aloud throughout their judgments was implemented to facilitate understanding of quantitative findings. Consistency ratios were calculated as a measure of logical judgment performance within AHP. If consistency ratios exceeded 0.2, we explored reasons for inconsistency. RESULTS: We interviewed 86 patients and generated preference weights for criteria. Patients rated the injection's effect on visual function the highest (0.44), followed by the frequency of monitoring visits (0.18), approval status (0.13), injection frequency (0.13), and side effects (0.12). Inconsistency in judgments was prevalent at the subcriteria level. Whereas much of the observed inconsistency was due to an excessive use of high/extreme value judgments, these judgments seemed to result from patients reasonably trying to highlight their strong preferences. CONCLUSION: Our study combines quantitative with qualitative data to explore patients' preference weights and decision processes using the AHP. It suggests that the type of inconsistency observed in judgments of AMD patients mostly results from rational decision making, not from error or lack of understanding. Further research should address which type and extent of inconsistency might be acceptable in different AHP settings. PMID- 27255774 TI - Effects of the intramyocardial implantation of stromal vascular fraction in patients with chronic ischemic cardiomyopathy. AB - BACKGROUND: Stromal vascular fraction (SVF) can easily be obtained from a mini lipoaspirate procedure of fat tissue. The SVF contains a mixture of cells including ADSCs and growth factors and has been depleted of the adipocyte (fat cell) population. We evaluated the safety and efficacy of administering SVF intra myocardially into patients with chronic ischemic cardiomyopathy. METHODS: A total of 28 patients underwent a local tumescent liposuction procedure to remove approximately 60 ml of fat tissue. The fat was separated to isolate the SVF and the cells were delivered into the akinetic myocardial scar region using a transendocardial delivery system (MyoCath((r))) in patients who had experienced a previous myocardial infarct. The subjects were then monitored for adverse events, ejection fraction via echocardiogram and six-minute walk test (6MWT) over a period of 6 months. RESULTS: The average EF was 29 % at baseline and significantly increased to 35 % at both 3 and 6 months. Patients walked an average of 349 m at baseline and demonstrated a statistically significant improvement at 3 and 6 months' post treatment of more than 80 m. CONCLUSIONS: Overall, patients were pleased with the treatment results. More importantly, the procedure demonstrated a strong safety profile with no severe adverse events or complications linked to the therapy. Trial registration NCT01502514 Name of registry: http://www.clinicaltrials.gov URL: https://www.clinicaltrials.gov/ct2/show/NCT01502514?term=adipose+cells+heart&rank 4 Date of registration: December 27, 2011 Date of enrollment: January 2012. PMID- 27255775 TI - Improvement on D-xylose to Xylitol Biotransformation by Candida guilliermondii Using Cells Permeabilized with Triton X-100 and Selected Process Conditions. AB - Cells of Candida guilliermondii permeabilized with Triton X-100 were able to efficiently produce xylitol from a medium composed only by D-xylose and MgCl2.6H2O in potassium phosphate buffer, at 35 degrees C and pH 6.5. Under these conditions, the results were similar to those obtained when cofactor and co substrate or nutrients were added to the medium (about 95 % D-xylose was assimilated producing 42 g/L of xylitol, corresponding to 0.80 g/g yield and 2.65 g/L h volumetric productivity). Furthermore, the permeabilized cells kept the D xylose assimilation in about 90 % and the xylitol production in approx. 40 g/L during three bioconversion cycles of 16 h each. These values are highly relevant when compared to others reported in the literature using enzyme technology and fermentative process, thereby demonstrating the effectiveness of the proposed method. The present study reveals that the use of permeabilized cells is an interesting alternative to obtain high xylitol productivity using low cost medium formulation. This approach may allow the future development of xylitol production from xylose present in lignocellulosic biomass, with additional potential for implementation in biorefinery strategies. PMID- 27255776 TI - Individual neurons in the caudal fastigial oculomotor region convey information on both macro- and microsaccades. AB - Recent studies have suggested that microsaccades, the small amplitude saccades made during fixation, are precisely controlled. Two lines of evidence suggest that the cerebellum plays a key role not only in improving the accuracy of macrosaccades but also of microsaccades. First, lesions of the fastigial oculomotor regions (FOR) cause horizontal dysmetria of both micro- and macrosaccades. Secondly, our previous work on Purkinje cell simple spikes in the oculomotor vermis (OV) has established qualitatively similar response preferences for these two groups of saccades. In this work, we investigated the control signals for micro- and macrosaccades in the FOR, the target of OV Purkinje cell axons. We found that the same FOR neurons discharged for micro- and macrosaccades. For both groups of saccades, FOR neurons exhibited very similar dependencies of their discharge strength on direction and amplitude and very similar burst onset time differences for ipsi- and contraversive saccades and, in both, response duration reflected saccade duration, at least at the population level. An intriguing characteristic of microsaccade-related responses is that immediate pre-saccadic firing rates decreased with distance to the target center, a pattern that strikingly parallels the eye position dependency of both microsaccade metrics and frequency, which may suggest a potential neural mechanism underlying the role of FOR in fixation. Irrespective of this specific consideration, our study supports the view that microsaccades and macrosaccades share the same cerebellar circuitry and, in general, further strengthens the notion of a microsaccade-macrosaccade continuum. PMID- 27255777 TI - Development and validation of the Slovenian drug-related problem classification system based on the PCNE classification V 6.2. AB - Background Classifying drug-related problems increases pharmacists' awareness of patients' drug-related needs and supports the development of counselling skills through increased awareness of the nature and frequency of drug-related problems. No standardised classification system was used in daily pharmacy practice in Slovenia. Objective To translate, upgrade and validate the Pharmaceutical Care Network Europe (PCNE) classification V 6.2 for use in Slovenian community pharmacies. Setting Expert panel meetings at the Faculty of Pharmacy and home based classification validation. Methods The PCNE classification V 6.2 was translated to Slovenian language by forward-backward translation procedure. An expert panel consisting of nine practicing pharmacists upgraded the content of the translated version. Thirty-one community pharmacists validated this version with the PCNE set of 18 patient cases by coding problems, risk factors and interventions they believed were present in each case. The expert panel discussed the results and upgraded the classification accordingly. Afterwards, 33 community pharmacists validated the upgraded version with a set of 40 actual Slovenian pharmacy patient cases. Based on the results, the expert panel formed a final version of the classification. Main outcome measure Coding consistency between community pharmacists. Results The expert panel performed some major modifications to the PCNE classification V 6.2: the potential problem was added as a sub domain to problems domain; the term adverse drug event was used instead of adverse drug reaction; the causes domain was renamed to risk factors and its sub domains were organized into prescribing, dispensing and use of drugs; dispensing errors were specified; use of drugs was organized into intentional and unintentional use of drugs; the sub domains in the interventions domain were divided according to the communication and agreement with the prescriber. The average coding consistencies in the first validation study were 75 % (+/-16 %) for problems, 74 % (+/-20 %) for risk factors and 94 % (+/-10 %) for interventions. The average coding consistencies in the second validation study were 83 % (+/-16 %) for problems, 85 % (+/-17 %) for risk factors and 80 % (+/-20 %) for interventions. Conclusion A drug-related problem classification for use in Slovenian community pharmacies was developed based on The PCNE classification V 6.2. The validation studies demonstrated high coding consistencies. PMID- 27255778 TI - Development of a fresh cadaver model for instruction of ultrasound-guided breast biopsy during the surgery clerkship: pre-test and post-test results among third year medical students. AB - BACKGROUND: The aim of our study was to determine if a fresh cadaver model is a viable method for teaching ultrasound (US)-guided breast biopsy of palpable breast lesions. METHODS: Third-year medical students were assessed both preinstruction and postinstruction on their ability to perform US-guided needle aspiration or biopsy of artificially created masses using a 10-item checklist. RESULTS: Forty-one third-year medical students completed the cadaver laboratory as part of the surgery clerkship. Eight items on the checklist were found to be significantly different between pre-testing and post-testing. The mean preinstruction score was 2.4, whereas the mean postinstruction score was 7.10 (P < .001). CONCLUSIONS: Fresh cadaver models have been widely used in medical education. However, there are few fresh cadaver models that provide instruction on procedures done in the outpatient setting. Our model was found to be an effective method for the instruction of US-guided breast biopsy among medical students. PMID- 27255779 TI - "Face validity" is not a legitimate type of validity evidence! AB - The American Journal of Surgery (AJS) is a long-standing leader among surgery publications and has published high-quality research dating back to 1926. To preserve AJS's reputation, it is necessary to identify issues that may affect the journal, and subsequently the broader field of surgery, in a negative way, and attempt to resolve those issues. To that end, I would like to address the issue of citing "face validity" as a type of validity evidence. In a review of AJS articles since 2006, 30 articles have consisted of researchers citing face validity as part of their validity evidence. This is problematic because validity theorists (scholars who dedicate their careers to studying validity and what constitutes acceptable types of validity evidence) have universally agreed there is no such thing as "face validity". Thus, the purpose of this article is to encourage surgeons to study recent, and authoritative, works on validity theory, so they can better articulate the trustworthiness of their research findings and be more informed consumers of research. PMID- 27255780 TI - Diabetes is associated with perforated appendicitis: evidence from a population based study. AB - BACKGROUND: The purpose of this study was to investigate the relationship between perforated appendicitis and patient with diabetes using a population-based data set. METHODS: This study used data from the Longitudinal Health Insurance Database 2005 in Taiwan. We identified 4,806 patients hospitalized with acute appendicitis. The independent variable was whether a patient had ever received a diagnosis of diabetes before the index hospitalization. We performed a conditional logistic regression model to explore the odds ratio and its corresponding 95% confidence interval of perforated appendicitis. RESULTS: Rates of perforated appendicitis for patients with and those without diabetes were 46.2% and 28.3%, respectively. A chi-square test revealed that there was a significant difference in rates of perforated appendicitis between patients with and those without diabetes (P < .001). The conditional logistic regression model revealed that the adjusted odds ratio of perforated appendicitis for patients with diabetes was 1.35 (95% confidence interval = 1.11 to 1.65) compared with patients without diabetes. CONCLUSIONS: Our study demonstrated that a history of diabetes is an important factor with regard to the rate of perforated appendicitis. PMID- 27255781 TI - Risk factors associated with post-extubation stridor in the trauma intensive care unit. AB - BACKGROUND: Post-extubation stridor is an uncommon complication in medical intensive care units (ICUs) but has not been well studied in trauma patients. We sought to determine the incidence of reintubation due to stridor in trauma patients and describe associated risk factors. METHODS: A retrospective review of all intubated trauma patients was performed. Data collected included presence of stridor, demographic data, and details of intubation and extubation. RESULTS: Of all trauma patients reintubated, 31% were for stridor. Although female gender, age less than 18, blunt mechanism, and duration of intubation 5 days or more were associated with reintubation for stridor, endotracheal tube diameter was not. Mortality was not increased with reintubation. CONCLUSIONS: Trauma ICU patients are reintubated for stridor at a higher rate than medical ICU patients. Age, gender, blunt mechanism, and duration of intubation are risk factors for this complication. PMID- 27255782 TI - Outcomes of colonic diverticulitis according to the reason of immunosuppression. AB - BACKGROUND: The aims of this study were to analyze the relationship between the different causes of immunosuppression (IMS) and diverticulitis. METHODS: IMS patients admitted for colonic diverticulitis were included in the study. Patients were divided in 5 groups according to the reasons of IMS: group I, chronic corticosteroid therapy; group II, transplant patients; group III, malignant neoplasm disease; group IV, chronic renal failure; group V, others immunosuppressant treatment. Rate of emergency surgery, outcomes in terms of postoperative mortality, and recurrence rate after nonoperative management were analyzed according to the reason of IMS. RESULTS: Emergency surgery was performed in 76 patients (39.3%). It was needed more frequently in group I. Overall, postoperative mortality was of 31.6% and recurrence rate after successful nonoperative management occurred in 30 patients (27.8%). No differences were observed among the groups. CONCLUSIONS: The rate of emergency surgery in IMS patients at the first episode of acute colonic diverticulitis is high. Elective surgery in IMS patients should be individually indicated according to persistence of symptoms or early recurrences. PMID- 27255784 TI - Long term effects of nocturnal hypoxia and urinary uric acid excretion: How much linked to COPD and OSAS? PMID- 27255783 TI - Resistance and Security Index of Networks: Structural Information Perspective of Network Security. AB - Recently, Li and Pan defined the metric of the K-dimensional structure entropy of a structured noisy dataset G to be the information that controls the formation of the K-dimensional structure of G that is evolved by the rules, order and laws of G, excluding the random variations that occur in G. Here, we propose the notion of resistance of networks based on the one- and two-dimensional structural information of graphs. Given a graph G, we define the resistance of G, written , as the greatest overall number of bits required to determine the code of the module that is accessible via random walks with stationary distribution in G, from which the random walks cannot escape. We show that the resistance of networks follows the resistance law of networks, that is, for a network G, the resistance of G is , where and are the one- and two-dimensional structure entropies of G, respectively. Based on the resistance law, we define the security index of a network G to be the normalised resistance of G, that is, . We show that the resistance and security index are both well-defined measures for the security of the networks. PMID- 27255785 TI - Secondhand smoke exposure in children: It is time to move forward. PMID- 27255787 TI - Haematopoietic stem cell transplantation for sickle cell disease - current practice and new approaches. AB - Sickle cell disease is an inherited disorder that affects over 5 million people worldwide. Current maintenance therapy has been successful in reducing complications and enhancing life expectancy; yet subclinical complications persist. To date, allogeneic haematopoietic stem cell transplant (HSCT) remains the only available curative therapy for sickle cell disease. With declining incidences of rejection and transplant- related mortality, disease-free survival after human leucocyte antigen-identical sibling transplant exceeds 90%. However, the majority of individuals with sickle cell disease do not have an human leucocyte antigen (HLA)-identical sibling; therefore, research is expanding to focus on new approaches to alternative donor transplant. Advances in supportive care and conditioning regimens have led to expansion of the pool of donors to unrelated donors and haploidentical donors. Challenges remain in improving the safety and efficacy of HSCT from alternate donors. Early results from gene therapy may provide another curative option in patients with sickle cell disease. These approaches show early promise, but larger, longitudinal studies are needed to better determine the optimal clinical circumstances for transplant in sickle cell disease. PMID- 27255786 TI - The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria. AB - The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186 G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC). The rs867186-GG genotype was more frequent in CC (4.1%) than SM (0.6%, P = 0.002). The rs867186-G variant was associated with increased sEPCR levels and sEPCR was lower in children with SM than CC (P < 0.001). Among SM children, those who had a second SM episode showed a trend toward lower plasma sEPCR both at initial admission and at 6-month follow-up compared to those without repeated SM (P = 0.06 for both). The study findings support a role for sEPCR in severe malaria pathogenesis and emphasize a distinct role of sEPCR in malaria as compared to other infectious diseases. PMID- 27255788 TI - Sleep-Related Disorders in Children with Attention-Deficit Hyperactivity Disorder: Preliminary Results of a Full Sleep Assessment Study. AB - BACKGROUND AND METHODS: We present the preliminary results of a prospective case control sleep study in children with a diagnosis of attention-deficit hyperactivity disorder (ADHD). A deep sleep assessment including sleep questionnaires, sleep habits, a video-polysomnographic recording with full high density electroencephalography (EEG) and cardiorespiratory polygraphy, multiple sleep latency test, and 1-week actigraphic recording were performed to verify whether children with ADHD may be classified into one of the following five phenotypes: (1) hypoarousal state, resembling narcolepsy, which may be considered a "primary" form of ADHD; (2) delayed sleep onset insomnia; (3) sleep-disordered breathing; (4) restless legs syndrome and/or periodic limb movements; and (5) sleep epilepsy and/or EEG interictal epileptiform discharges. RESULTS: Fifteen consecutive outpatients with ADHD were recruited (two female, mean age 10.6 +/- 2.2, age range 8-13.7 years) over 6 months. The narcolepsy-like sleep phenotype was observed in three children, the sleep onset insomnia phenotype was observed in one child, mild obstructive sleep apnea was observed in three children, sleep hyperkinesia and/or PLMs were observed in five children, while IEDs and or nocturnal epilepsy were observed in three children. Depending on the sleep phenotype, children received melatonin, iron supplementation, antiepileptic drugs, or stimulants. CONCLUSIONS: Our study further highlights the need to design an efficient sleep diagnostic algorithm for children with ADHD, thereby more accurately identifying cases in which a full sleep assessment is indicated. PMID- 27255789 TI - Complexes trans-Pt(BODIPY)X(PEt3)2: excitation energy-dependent fluorescence and phosphorescence emissions, oxygen sensing and photocatalysis. AB - We report on five new complexes with the general formula trans-Pt(BODIPY)X(PEt3)2 (), where the platinum(ii) ion is sigma-bonded to a 4,4-difluoro-4-bora-3a,4a diaza-s-indacen-8-yl (BODIPY) and an anionic ligand X(-) (X(-) = Cl(-), I(-), NO2(-), NCS(-), CH3(-)). All five complexes were characterized by multinuclear NMR, electronic absorption and luminescence spectroscopy and by X-ray diffraction analysis. Four of these complexes show efficient intersystem crossing (ISC) from an excited singlet state to a BODIPY-centred T1 state and exhibit dual fluorescence and phosphorescence emission from the BODIPY ligand. In , the fluorescence is almost completely quenched, whereas the phosphorescence quantum yield reaches a value of 40%. The rate of ISC and the ratio of phosphorescence to fluorescence emissions depend on the excitation wavelength (i.e. on which specific transition is excited). The performance of these complexes as one component oxygen sensors and their photocatalytic activities were tested by Stern Volmer quenching experiments and by monitoring the oxidation of 1,5 dihydroxynaphthalene with (1)O2 generated from the long-lived triplet state of the sensitizer by triplet-triplet annihilation with (3)O2. Exceptionally high (1)O2 generation quantum yields of up to near unity were obtained. PMID- 27255790 TI - Distress in significant others of patients with chronic fatigue syndrome: A systematic review of the literature. AB - PURPOSE: The objective of this study was to systematically review existing empirical research assessing levels and correlates of distress in significant others of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). METHODS: Systematic searches in CINAHL, Web of Science and PsycINFO were conducted in August 2014. The search was repeated in January 2015 to check for newly published articles. Studies published in English with quantitative, qualitative, or mixed designs exploring distress, poor subjective health, poor mental health, reduced quality of life and well-being, and symptoms of depression and anxiety in significant others (>18 years) of children and adults with CFS/ME were included. Quality appraisal of included studies was carried out. Quantitative and qualitative studies were summarized separately. RESULTS: Six articles met eligibility criteria. Two quantitative studies with significant others of adult patients, and one quantitative and two mixed-methods studies with significant others of child patients showed moderate to high levels of distress. One qualitative study (adult patients) found minimal evidence of distress and that acceptance of CFS/ME was related to better adjustment. In the quantitative and mixed-methods studies, significant others who attributed some level of responsibility for symptoms to the patient, or who were female, or whose partners had poorer mental health, had higher levels of distress. CONCLUSIONS: The small number of studies to date, the contrary evidence from a qualitative study, and the limited data available on levels of distress in significant others of patients with CFS/ME mean that our conclusion that distress levels are elevated is provisional. We recommend that future qualitative studies focus on this particular topic. Further longitudinal studies exploring correlates of distress within the context of a predictive theoretical model would be helpful. Statement of contribution What is already known on this subject? Chronic fatigue syndrome (CFS/ME) entails considerable economic, social, and personal costs. Uncertainties exist around diagnosis and management. This may lead to particular difficulties for significant others trying to support patients. What does this study add? Few studies have examined distress and its correlates in significant others of people with CFS/ME. Significant others report elevated levels of distress on quantitative measures. PMID- 27255791 TI - Synergistic Effect of Compounds from a Chinese Herb: Compatibility and Dose Optimization of Compounds from N-Butanol Extract of Ipomoea stolonifera. AB - The herbal medicine Ipomoea stolonifera (I. stolonifera) has previously been shown to have considerable anti-inflammatory potential in vivo and in vitro. To establish a method for exploring the synergistic effects of multiple compounds, we study the compatibility and dose optimization of compounds isolated from n butanol extract of I. stolonifera (BE-IS). Raw264.7 cell was treated with lipopolysaccharide (LPS) in the presence of compounds from BE-IS, namely scopoletin, umbelliferone, esculetin, hesperetin and curcumin, using the orthogonal design, uniform design and median-effect method. To verify the best efficacy of principal constituents in vivo, the uniform design was used in the croton oil-induced mouse ear edema model. The results from LPS-induced the production of prostaglandin E2 (PGE2) show that, esculetin, curcumin and hesperetin were the principal constituents that had synergistic effects when used at the optimal ratio. Additionally, the principal constituents were found to work synergistically in the croton oil-induced mouse ear edema model at low doses. It turned out that the three experimental optimization and analysis methods (orthogonal design, uniform design and median-effect method) can be effectively used to solve both compatibility and dose optimization for combined use of multiple compounds. PMID- 27255793 TI - The bactericidal activity of glutaraldehyde-impregnated polyurethane. AB - Although glutaraldehyde is known to be bactericidal in solution, its potential use to create novel antibacterial polymers suitable for use in healthcare environments has not been evaluated. Here, novel materials were prepared in which glutaraldehyde was either incorporated into polyurethane using a simple "swell encapsulation-shrink" method (hereafter referred to as "glutaraldehyde impregnated polyurethane"), or simply applied to the polymer surface (hereafter referred to as "glutaraldehyde-coated polyurethane"). The antibacterial activity of glutaraldehyde-impregnated and glutaraldehyde-coated polyurethane samples was tested against Escherichia coli and Staphylococcus aureus. Glutaraldehyde impregnated polyurethane resulted in a 99.9% reduction in the numbers of E. coli within 2 h and a similar reduction of S. aureus within 1 h, whereas only a minimal reduction in bacterial numbers was observed when the biocide was bound to the polymer surface. After 15 days, however, the bactericidal activity of the impregnated material was substantially reduced presumably due to polymerization of glutaraldehyde. Thus, although glutaraldehyde retains antibacterial activity when impregnated into polyurethane, activity is not maintained for extended periods of time. Future work should examine the potential of chemical modification of glutaraldehyde and/or polyurethane to improve the useful lifespan of this novel antibacterial polymer. PMID- 27255792 TI - MutSbeta promotes trinucleotide repeat expansion by recruiting DNA polymerase beta to nascent (CAG)n or (CTG)n hairpins for error-prone DNA synthesis. AB - Expansion of (CAG)*(CTG) repeats causes a number of familial neurodegenerative disorders. Although the underlying mechanism remains largely unknown, components involved in DNA mismatch repair, particularly mismatch recognition protein MutSbeta (a MSH2-MSH3 heterodimer), are implicated in (CAG)*(CTG) repeat expansion. In addition to recognizing small insertion-deletion loop-outs, MutSbeta also specifically binds DNA hairpin imperfect heteroduplexes formed within (CAG)n*(CTG)n sequences. However, whether or not and how MutSbeta binding triggers expansion of (CAG)*(CTG) repeats remain unknown. We show here that purified recombinant MutSbeta physically interacts with DNA polymerase beta (Polbeta) and stimulates Polbeta-catalyzed (CAG)n or (CTG)n hairpin retention. Consistent with these in vitro observations, MutSbeta and Polbeta interact with each other in vivo, and colocalize at (CAG)*(CTG) repeats during DNA replication. Our data support a model for error-prone processing of (CAG)n or (CTG)n hairpins by MutSbeta and Polbeta during DNA replication and/or repair: MutSbeta recognizes (CAG)n or (CTG)n hairpins formed in the nascent DNA strand, and recruits Polbeta to the complex, which then utilizes the hairpin as a primer for extension, leading to (CAG)*(CTG) repeat expansion. This study provides a novel mechanism for trinucleotide repeat expansion in both dividing and non-dividing cells. PMID- 27255794 TI - A nonlinear controlling function of geological features on magmatic-hydrothermal mineralization. AB - This paper reports a nonlinear controlling function of geological features on magmatic-hydrothermal mineralization, and proposes an alternative method to measure the spatial relationships between geological features and mineral deposits using multifractal singularity theory. It was observed that the greater the proximity to geological controlling features, the greater the number of mineral deposits developed, indicating a nonlinear spatial relationship between these features and mineral deposits. This phenomenon can be quantified using the relationship between the numbers of mineral deposits N(epsilon) of a D dimensional set and the scale of epsilon. The density of mineral deposits can be expressed as rho(epsilon) = Cepsilon(-(De-a)), where epsilon is the buffer width of geological controlling features, De is Euclidean dimension of space (=2 in this case), a is singularity index, and C is a constant. The expression can be rewritten as rho = Cepsilon(a-2). When a < 2, there is a significant spatial correlation between specific geological features and mineral deposits; lower a values indicate a more significant spatial correlation. This nonlinear relationship and the advantages of this method were illustrated using a case study from Fujian Province in China and a case study from Baguio district in Philippines. PMID- 27255795 TI - Bibliometric analysis of the scientific production in implantology (2009-2013). AB - OBJECTIVES: To quantify, using bibliometric indicators, the scientific productivity of researchers, organizations, and countries, publishing articles on implantology in dental journals indexed in Journal Citation Reports between 2009 and 2013. MATERIALS AND METHODS: Published texts were identified by applying the truncated search term "implant*." Document type was limited to "Article." Records were manually refined and normalized to unify terms and to remove typographical, transcription, and/or indexing errors. RESULTS: A total of 6088 articles were located. A progressive increase in the rate of publication was observed, especially between 2010 and 2012. This increase was clearly linked to increased collaboration between authors, institutions, and countries. Keywords appeared at a frequency of 3.1 per document. The journals Clinical Oral Implants Research and International Journal of Oral & Maxillofacial Implants published the highest numbers of articles. CONCLUSIONS: This study revealed a significant growth in implant dentistry literature in terms of the total number of journals, number of authors, organizations, and author collaborations. Most key bibliometric indicators demonstrated upward trends. PMID- 27255796 TI - Microgobius meeki as a potential bio-indicator of habitat disturbance in shallow estuarine areas: a useful tool for the assessment of estuarine quality. AB - The relationships between changes in habitat quality (disturbed and undisturbed sites) and the population parameters (density, size distribution, reproductive activity and diet) of a goby Microgobius meeki were investigated in a tropical estuary to assess its value as an indicator of anthropogenic changes, predominantly the effects of sedimentation and mangrove removal in shallow estuarine areas. Fish sampling surveys were conducted bimonthly between June 2009 and May 2010 over the entire estuarine gradient of the Paraguacu River estuary, located on the central Brazilian coast. A predictive model was developed to assess the population changes of this species in 10 other tropical estuaries with different dimensions, basin features and distinct levels of anthropogenic disturbance. General linear models were used to relate the population structure of M. meeki to sediment type, habitat type resulting from mangrove conservation status, anthropogenic pressure and environmental characteristics such as salinity, dissolved oxygen concentrations and temperature. Sediment type and the presence of mangrove forests were the most effective predictors of local variability in the population structure of M. meeki. Individuals with mature gonads and high rates of feeding activity were associated predominantly with undisturbed habitats. Estuaries and estuarine sectors with high levels of sedimentation in shallow marginal areas, anthropogenic pressure from domestic and industrial effluents, and evidence of mangrove deforestation yielded the lowest capture rates of both juvenile and adult M. meeki. Based on these findings, M. meeki is identified as a potential indicator of the consequences of anthropogenic disturbance in transitional waters. A simple, but efficient collection protocol, in which overt signs of distress can be promptly observed is proposed. Testing the generality of this approach across different systems might prove useful in a broader conservation biology context. PMID- 27255797 TI - Endovascular retrograde recanalization in Asian critical limb ischaemia patients. AB - BACKGROUND: To evaluate endovascular retrograde recanalization of critical limb ischaemia (CLI) patients with chronic total occlusions (CTOs) in an Asian population. METHODS: We conducted a single centre-based retrospective review of CLI patients with CTOs who had undergone endovascular retrograde recanalization using the subintimal arterial flossing with antegrade-retrograde intervention technique. RESULTS: A total of 40 CLI patients with CTOs underwent endovascular intervention. The median age was 71 years; 67.5% were males and Chinese accounted for 65% of the patients, of which 55% were in Rutherford category 6, 37.5% in category 5 and 7.5% in category 4. Antegrade-retrograde access was performed via the femoral artery in 39 cases and the brachial artery in one case for the proximal puncture, and the following arteries for the distal puncture: superficial femoral, n = 4 (10%); popliteal, n = 4 (10%); anterior tibial, n = 12 (30%); dorsalis pedis, n = 9 (22.5%); peroneal, n = 4 (10%) and posterior tibial, n = 7 (17.5%). Technical success was high at 92.5% (n = 37). After intervention, 25% (n = 10) had below-knee triple vessel runoff, 52.5% (n = 21) had double vessel runoff and 15.0% (n = 6) had single vessel runoff. Stenting for target vessel dissections was required in 12 patients. There were two cases of significant bleeding; one common femoral artery pseudoaneurysm was treated with ultrasound-guided thrombin injection and another case of distal puncture site bleeding only required compression. Limb salvage at 1 year was 92.5% (n = 37). CONCLUSION: The subintimal arterial flossing with antegrade-retrograde intervention technique is safe with high technical success rates and acceptable outcomes in Asian CLI patients with CTOs. PMID- 27255798 TI - Using Fractal and Local Binary Pattern Features for Classification of ECOG Motor Imagery Tasks Obtained from the Right Brain Hemisphere. AB - The feature extraction and classification of brain signal is very significant in brain-computer interface (BCI). In this study, we describe an algorithm for motor imagery (MI) classification of electrocorticogram (ECoG)-based BCI. The proposed approach employs multi-resolution fractal measures and local binary pattern (LBP) operators to form a combined feature for characterizing an ECoG epoch recording from the right hemisphere of the brain. A classifier is trained by using the gradient boosting in conjunction with ordinary least squares (OLS) method. The fractal intercept, lacunarity and LBP features are extracted to classify imagined movements of either the left small finger or the tongue. Experimental results on dataset I of BCI competition III demonstrate the superior performance of our method. The cross-validation accuracy and accuracy is 90.6% and 95%, respectively. Furthermore, the low computational burden of this method makes it a promising candidate for real-time BCI systems. PMID- 27255799 TI - Classification of EEG Single Trial Microstates Using Local Global Graphs and Discrete Hidden Markov Models. AB - We present a novel synergistic methodology for the spatio-temporal analysis of single Electroencephalogram (EEG) trials. This new methodology is based on the novel synergy of Local Global Graph (LG graph) to characterize define the structural features of the EEG topography as a global descriptor for robust comparison of dominant topographies (microstates) and Hidden Markov Models (HMM) to model the topographic sequence in a unique way. In particular, the LG graph descriptor defines similarity and distance measures that can be successfully used for the difficult comparison of the extracted LG graphs in the presence of noise. In addition, hidden states represent periods of stationary distribution of topographies that constitute the equivalent of the microstates in the model. The transitions between the different microstates and the formed syntactic patterns can reveal differences in the processing of the input stimulus between different pathologies. We train the HMM model to learn the transitions between the different microstates and express the syntactic patterns that appear in the single trials in a compact and efficient way. We applied this methodology in single trials consisting of normal subjects and patients with Progressive Mild Cognitive Impairment (PMCI) to discriminate these two groups. The classification results show that this approach is capable to efficiently discriminate between control and Progressive MCI single trials. Results indicate that HMMs provide physiologically meaningful results that can be used in the syntactic analysis of Event Related Potentials. PMID- 27255800 TI - Intrinsic Plasticity for Natural Competition in Koniocortex-Like Neural Networks. AB - In this paper, we use the neural property known as intrinsic plasticity to develop neural network models that resemble the koniocortex, the fourth layer of sensory cortices. These models evolved from a very basic two-layered neural network to a complex associative koniocortex network. In the initial network, intrinsic and synaptic plasticity govern the shifting of the activation function, and the modification of synaptic weights, respectively. In this first version, competition is forced, so that the most activated neuron is arbitrarily set to one and the others to zero, while in the second, competition occurs naturally due to inhibition between second layer neurons. In the third version of the network, whose architecture is similar to the koniocortex, competition also occurs naturally owing to the interplay between inhibitory interneurons and synaptic and intrinsic plasticity. A more complex associative neural network was developed based on this basic koniocortex-like neural network, capable of dealing with incomplete patterns and ideally suited to operating similarly to a learning vector quantization network. We also discuss the biological plausibility of the networks and their role in a more complex thalamocortical model. PMID- 27255801 TI - Adaptation and Validation of the Basque Version of the Emotional Creativity Inventory in Higher Education. AB - Emotional creativity is defined as the ability to feel and express emotions in a new, effective and authentic way. There are currently no Basque-language self report instruments to provide valid and reliable measures of this construct. Thus, this paper describes the process of adapting and validating the Emotional Creativity Inventory (ECI) for the Basque-speaking population. The sample was comprised of 594 higher education students (388 women and 206 men) aged between 18 and 32 years old (Mage = 20.47; SD = 2.48). The Basque version of the ECI was administered along with the TMMS-23, NEO PI-R, and PANAS. The results of exploratory and confirmatory factor analyses on the Basque ECI corroborated the original scale's three-factor structure (preparedness, novelty, and effectiveness/authenticity). Those dimensions showed acceptable indexes of internal consistency (alpha = .80, .83, and .83) and temporal stability (r = .70, .69, and .74). The study also provided some evidence of external validity (p < .05) based on the relationships found between emotional creativity and emotional intelligence, personality, affect, and sex. The Basque ECI can be regarded as a useful tool to evaluate perceived emotional creativity during the preparation and verification phases of the creative process. PMID- 27255802 TI - Assessment of oxidative stress responses and the cytotoxic and genotoxic potential of the herbicide tembotrione in HepG2 cells. AB - Tembotrione is a triketone herbicide, usually used for post-emergence weed control in corn. Currently, there is little or no published data on its genotoxicity to human cells either in vitro or in vivo. This study evaluated the impact of acute (4 and 24 h) exposure to low concentrations of tembotrione [corresponding to the acceptable daily intake (0.17 MUg/mL), residential exposure level (0.002 MUg/mL) and acceptable operator exposure level (0.0012 MUg/mL)] on human hepatocellular carcinoma cell line HepG2, using biomarkers of oxidative stress, CCK-8 colorimetric assay for cell viability, alkaline comet assay, and cytokinesis-block micronucleus "cytome" assay. Tembotrione applied at concentrations likely to be encountered in occupational and residential exposures induced cytogenetic outcomes in non-target cells despite non-significant changes in the values of oxidative stress biomarkers. We assume that the observed effects were mainly the consequence of impaired metabolic pathways in HepG2 cells due to the inhibition of the enzyme 4-hydroxyphenyl-pyruvate-dioxygenase by tembotrione, which possibly caused a depletion of folate levels leading to excess formation of nuclear buds in the affected cells. Regardless of the fact that tembotrione was previously reported negative for mutations and chromosome aberrations in vitro, our findings call for more precaution in its use. PMID- 27255803 TI - Urine and serum biomonitoring of exposure to environmental estrogens II: Soy isoflavones and zearalenone in pregnant women. AB - Urine and serum biomonitoring was used to measure internal exposure to selected dietary estrogens in a cohort of 30 pregnant women. Exposure was measured over a period comprising one-half day in the field (6 h) and one day in a clinic (24 h). Biomonitoring of the dietary phytoestrogens genistein (GEN), daidzein (DDZ) and equol (EQ), as well as the mycoestrogen, zearalenone (ZEN) and its congeners, was conducted using UPLC-MS/MS. Biomonitoring revealed evidence of internal exposure to naturally occurring dietary estrogens during pregnancy. Urinary concentrations of total GEN, DDZ and EQ were similar to levels reported for general adult U.S. POPULATION: Measurable concentrations of total (parent and metabolites) GEN, DDZ and EQ were present in 240, 207 and 2 of 270 serum samples, respectively. Six out of 30 subjects had measurable concentrations of unconjugated GEN and/or DDZ in serum between 0.6 and 7.1 nM. Urine to serum total isoflavone ratios for GEN, DDZ and EQ were 13, 47, and 180, respectively. ZEN and its reductive metabolite, alpha-zearalenol (alpha-ZEL), were present in pregnant women (11 out of 30 subjects) as conjugates at levels near the limit of quantification. The average total urinary concentration was 0.10 MUg/L for ZEN and 0.11 MUg/L for alpha-ZEL. PMID- 27255804 TI - Probabilistic assessment of exposure to cosmetic products by French children aged 0-3 years. AB - Very few exposure data are available for children in Europe and worldwide. The aim of this study was to assess the exposure to cosmetic products used on children aged 0-3 years using recent consumption data generated for the French population. Exposure was assessed using a probabilistic method for 24 products including cleanser, skin care, fragrance, solar and bottom products. The exposure data obtained in this study for children aged 0-3 years were higher than the values fixed by the SCCS for all common products: liquid shampoo, face moisturizer cream, toothpaste, shower gel and body moisturizer cream. Exposure was assessed for the first time for many products such as sunscreens, Eau de toilette and massage products. These new French exposure values will be useful for safety assessors and for safety agencies. PMID- 27255805 TI - Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology. AB - AIM: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). MATERIALS & METHODS: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. RESULTS: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. CONCLUSION: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH. PMID- 27255806 TI - Interobserver Reliability of Peripheral Muscle Strength Tests and Short Physical Performance Battery in Patients With Chronic Obstructive Pulmonary Disease: A Prospective Observational Study. AB - OBJECTIVE: To evaluate the interobserver reliability of the Short Physical Performance Battery (SPPB) and hand dynamometry when measuring isometric muscle strength in people with chronic obstructive pulmonary disease (COPD). DESIGN: Reliability study. Each patient was assessed by a pulmonology physician and a physical therapist in 2 separate sessions 7 to 14 days apart (mean, 9.8+/-0.8d). Each rater was blinded to the other's results. SETTING: Pneumology unit of a public hospital. PARTICIPANTS: Random sample of outpatients with stable COPD (N=30). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SPPB and muscle strength (kg) using electronic handgrip and handheld dynamometers. Reliability was assessed with intraclass correlation coefficients (ICCs), standard error of measurement values, and Bland-Altman plots. ICCs were calculated for the SPPB summary score and for its 3 subscales. RESULTS: The ICCs for the overall reliability of the SPPB summary score and for grip and quadriceps strength were .82 (95% confidence interval [CI], .62-.91), .97 (95% CI, .93-.98), and .76 (95% CI, .49-.88), respectively. The standard error of measurement values were .55 points, 1.30kg, and 1.22kg, respectively. The mean differences between the rater's scores were near zero for grip strength and SPPB summary score measures. The ICCs for the SPPB subscales were .84 (95% CI, .66-.92) for the chair subscale, .75 (95% CI, .48-.88) for gait, and .33 (95% CI, -.42 to .68) for balance. CONCLUSIONS: Interobserver reliability was good for quadriceps and handgrip dynamometry and for the SPPB summary score and its chair stand and gait speed subscales. Both pulmonary physicians and physical therapists can obtain and exchange the scores. Because the reliability of the balance subscale was questionable, it is better to use the SPPB summary score. PMID- 27255807 TI - Denosumab-associated hypocalcaemia: incidence, severity and patient characteristics in a tertiary hospital setting. AB - PURPOSE: Denosumab-associated hypocalcaemia (DAH) has been reported in patients with osteoporosis or metastatic bone disease and is associated with stages 4 and 5 chronic kidney disease (CKD, estimated glomerular filtration rate <30 mL/min/1.73m2 ). Other risk factors for hypocalcaemia have not been fully elucidated. We aimed to investigate the incidence of hypocalcaemia amongst patients receiving denosumab and to identify clinical features associated with this adverse event. METHODS: Retrospective cohort study between June 2013 and June 2014 of patients administered denosumab (60/120 mg) at a tertiary hospital in Melbourne, Australia, to identify the incidence of an albumin-adjusted serum calcium concentration <2.10 mmol/L or ionized calcium <1.13 mmol/L within 6 months of treatment. Univariable and multivariable logistic regression analyses were performed to identify clinical features associated with DAH. RESULTS: One hundred and fifty-five patients were administered denosumab (100 osteoporosis, 55 bone metastases). Twenty-two patients (14% [95%CI 9.1-20.7]) developed hypocalcaemia: 55% were men, and 55% had osteoporosis. Eighty-six per cent had a 25-hydroxyvitamin D concentration >50 nmol/L, and 91% were on calcium/colecalciferol supplementation. Stages 4 and 5 CKD (adjusted odd ratio [aOR] 4.71, 95%CI 1.61-13.79, p = 0.005) and male sex (aOR 4.30, 95%CI 1.69 10.96, p = 0.002) were associated with DAH. No patients were documented as having hypocalcaemic symptoms. One patient received intravenous calcium gluconate treatment. CONCLUSIONS: The incidence of denosumab-associated hypocalcaemia was 14% (95%CI 9.1-20.7) within 6 months of treatment despite widespread use of appropriate calcium/colecalciferol supplementation. Stages 4 and 5 CKD and male sex were associated with subsequent hypocalcaemia. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27255808 TI - Large-scale ordering of nanoparticles using viscoelastic shear processing. AB - Despite the availability of elaborate varieties of nanoparticles, their assembly into regular superstructures and photonic materials remains challenging. Here we show how flexible films of stacked polymer nanoparticles can be directly assembled in a roll-to-roll process using a bending-induced oscillatory shear technique. For sub-micron spherical nanoparticles, this gives elastomeric photonic crystals termed polymer opals showing extremely strong tunable structural colour. With oscillatory strain amplitudes of 300%, crystallization initiates at the wall and develops quickly across the bulk within only five oscillations. The resulting structure of random hexagonal close-packed layers is improved by shearing bidirectionally, alternating between two in-plane directions. Our theoretical framework indicates how the reduction in shear viscosity with increasing order of each layer accounts for these results, even when diffusion is totally absent. This general principle of shear ordering in viscoelastic media opens the way to manufacturable photonic materials, and forms a generic tool for ordering nanoparticles. PMID- 27255809 TI - "Less Than A Wife": A Study of Polycystic Ovary Syndrome Content in Teen and Women's Digital Magazines. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a major public health problem that affects women's physical and mental health. According to the US National Institutes of Health Office of Disease Prevention, there is a need to improve public awareness of the syndrome among health care providers and the public. Women's magazines are a type of "edutainment" that publish health content in addition to beauty, fashion, and entertainment content. These media have the potential to expose primarily female readers to content on PCOS and influence readers' beliefs and attitudes about women with PCOS. OBJECTIVE: The objective of this study was to explore how digital (online) teen and women's magazines portray women with PCOS. METHODS: We used data from the Alliance for Audited Media to identify popular digital teen and women's magazines with circulation rates >=1,000,001. We also included magazines with circulation rates 100,001-1,000,000 directed toward racial and ethnic minority readers. A search of magazine websites over a 1-month period in 2015 yielded 21 magazines (eg, Glamour, Cosmopolitan en Espanol, Essence, and O, The Oprah Magazine) and 170 articles containing "PCOS" and "polycystic ovary syndrome." Textual analysis using a grounded theory approach was used to identify themes. RESULTS: Articles depicted PCOS symptoms as a hindrance to women's social roles as wives and mothers and largely placed personal responsibility on women to improve their health. To a lesser extent, women were depicted as using their personal experience with PCOS to advocate for women's health. Experiences of Latina and African American women and adolescents with PCOS were absent from women's magazine articles. CONCLUSIONS: The findings can inform health education programs that teach women to be critical consumers of PCOS-related content in digital women's magazines. Future research on PCOS content in digital teen and women's magazines can help researchers, patients, and consumer groups engage with the media to increase public awareness of PCOS. PMID- 27255810 TI - Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects. AB - Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD. In this study, we assayed plasma profiles of ACCs in a cohort of healthy elderly control, MCI subjects, and AD patients. Compared with healthy controls or MCI subjects, AD patients showed significant lower plasma levels of several medium-chain ACCs. Furthermore, in AD patients, these lower concentrations were associated with lower prefrontal gray matter volumes and the presence of cognitive impairment. Interestingly, lower levels of medium-chain ACCs were also found to be associated with lower plasma levels of 2-hydroxybutyric acid. Overall, these findings suggest that altered metabolism of medium-chain ACCs and impaired ketogenesis can be metabolic features of AD. PMID- 27255811 TI - Differential effects of Cdh23(753A) on auditory and vestibular functional aging in C57BL/6J mice. AB - The C57BL/6J (B6) mouse strain carries a cadherin 23 mutation (Cdh23(753A), also known as Ahl), which affects inner ear structures and results in age-related hearing loss. The B6.CAST strain harbors the wild type Cdh23 gene, and hence, the influence of Ahl is absent. The purpose of the present study was to characterize the effect of age and gender on gravity receptor function in B6 and B6.CAST strains and to compare functional aging between auditory and vestibular modalities. Auditory sensitivity declined at significantly faster rates than gravity receptor sensitivity for both strains. Indeed, vestibular functional aging was minimal for both strains. The comparatively smaller loss of macular versus cochlear sensitivity in both the B6 and B6.CAST strains suggests that the contribution of Ahl to the aging of the vestibular system is minimal, and thus very different than its influence on aging of the auditory system. Alternatively, there exist unidentified genes or gene modifiers that serve to slow the degeneration of gravity receptor structures and maintain gravity receptor sensitivity into advanced age. PMID- 27255812 TI - Certified normal: Alzheimer's disease biomarkers and normative estimates of cognitive functioning. AB - Normative samples drawn from older populations may unintentionally include individuals with preclinical Alzheimer's disease (AD) pathology, resulting in reduced means, increased variability, and overestimation of age effects on cognitive performance. A total of 264 cognitively normal (Clinical Dementia Rating = 0) older adults were classified as biomarker negative ("Robust Normal," n = 177) or biomarker positive ("Preclinical Alzheimer's Disease" [PCAD], n = 87) based on amyloid imaging, cerebrospinal fluid biomarkers, and hippocampal volumes. PCAD participants performed worse than robust normals on nearly all cognitive measures. Removing PCAD participants from the normative sample yielded higher means and less variability on episodic memory, visuospatial ability, and executive functioning measures. These results were more pronounced in participants aged 75 years and older. Notably, removing PCAD participants from the sample significantly reduced age effects across all cognitive domains. Applying norms from the robust normal sample to a separate cohort did not improve Clinical Dementia Rating classification when using standard deviation cutoff scores. Overall, removing individuals with biomarker evidence of preclinical AD improves normative sample quality and substantially reduces age effects on cognitive performance but provides no substantive benefit for diagnostic classifications. PMID- 27255813 TI - Disrupted axon-glia interactions at the paranode in myelinated nerves cause axonal degeneration and neuronal cell death in the aged Caspr mutant mouse shambling. AB - Emerging evidence suggests that axonal degeneration is a disease mechanism in various neurodegenerative diseases and that the paranodes at the nodes of Ranvier may be the initial site of pathogenesis. We investigated the pathophysiology of the disease process in the central and peripheral nervous systems of a Caspr mutant mouse, shambling (shm), which is affected by disrupted paranodal structures and impaired nerve conduction of myelinated nerves. The shm mice manifest a progressive neurological phenotype as mice age. We found extensive axonal degeneration and a loss of neurons in the central nervous system and peripheral nervous system in aged shm mice. Axonal alteration of myelinated nerves was defined by abnormal distribution and expression of neurofilaments and derangements in the status of phosphorylated and non/de-phosphorylated neurofilaments. Autophagy-related structures were also accumulated in degenerated axons and neurons. In conclusion, our results suggest that disrupted axon-glia interactions at the paranode cause the cytoskeletal alteration in myelinated axons leading to neuronal cell death, and the process involves detrimental autophagy and aging as factors that promote the pathogenesis. PMID- 27255814 TI - Impaired thermoregulation and beneficial effects of thermoneutrality in the 3*Tg AD model of Alzheimer's disease. AB - The sharp rise in the incidence of Alzheimer's disease (AD) at an old age coincides with a reduction in energy metabolism and core body temperature. We found that the triple-transgenic mouse model of AD (3*Tg-AD) spontaneously develops a lower basal body temperature and is more vulnerable to a cold environment compared with age-matched controls. This was despite higher nonshivering thermogenic activity, as evidenced by brown adipose tissue norepinephrine content and uncoupling protein 1 expression. A 24-hour exposure to cold (4 degrees C) aggravated key neuropathologic markers of AD such as: tau phosphorylation, soluble amyloid beta concentrations, and synaptic protein loss in the cortex of 3*Tg-AD mice. Strikingly, raising the body temperature of aged 3*Tg-AD mice via exposure to a thermoneutral environment improved memory function and reduced amyloid and synaptic pathologies within a week. Our results suggest the presence of a vicious cycle between impaired thermoregulation and AD-like neuropathology, and it is proposed that correcting thermoregulatory deficits might be therapeutic in AD. PMID- 27255815 TI - Sirt1 deficiency protects cochlear cells and delays the early onset of age related hearing loss in C57BL/6 mice. AB - Hearing gradually declines with age in both animals and humans, and this condition is known as age-related hearing loss (AHL). Here, we investigated the effects of deficiency of Sirt1, a member of the mammalian sirtuin family, on age related cochlear pathology and associated hearing loss in C57BL/6 mice, a mouse model of early-onset AHL. Sirt1 deficiency reduced age-related oxidative damage of cochlear hair cells and spiral ganglion neurons and delayed the early onset of AHL. In cultured mouse inner ear cell lines, Sirt1 knockdown increased cell viability under oxidative stress conditions, induced nuclear translocation of Foxo3a, and increased acetylation status of Foxo3a. This resulted in increased activity of the antioxidant enzyme catalase. In young wild-type mice, both Sirt1 and Foxo3a proteins resided in the cytoplasm of the supporting cells within the organ of Corti of the cochlea. Therefore, our findings suggest that SIRT1 promotes early-onset AHL through suppressing FOXO3a-mediated oxidative stress resistance in the cochlea of C57BL/6 mice. PMID- 27255816 TI - Large cross-sectional study of presbycusis reveals rapid progressive decline in auditory temporal acuity. AB - The auditory system relies on extraordinarily precise timing cues for the accurate perception of speech, music, and object identification. Epidemiological research has documented the age-related progressive decline in hearing sensitivity that is known to be a major health concern for the elderly. Although smaller investigations indicate that auditory temporal processing also declines with age, such measures have not been included in larger studies. Temporal gap detection thresholds (TGDTs; an index of auditory temporal resolution) measured in 1071 listeners (aged 18-98 years) were shown to decline at a minimum rate of 1.05 ms (15%) per decade. Age was a significant predictor of TGDT when controlling for audibility (partial correlation) and when restricting analyses to persons with normal-hearing sensitivity (n = 434). The TGDTs were significantly better for males (3.5 ms; 51%) than females when averaged across the life span. These results highlight the need for indices of temporal processing in diagnostics, as treatment targets, and as factors in models of aging. PMID- 27255818 TI - Loss of ceramide synthase 2 activity, necessary for myelin biosynthesis, precedes tau pathology in the cortical pathogenesis of Alzheimer's disease. AB - The anatomical progression of neurofibrillary tangle pathology throughout Alzheimer's disease (AD) pathogenesis runs inverse to the pattern of developmental myelination, with the disease preferentially affecting thinly myelinated regions. Myelin is comprised 80% of lipids, and the prototypical myelin lipids, galactosylceramide, and sulfatide are critical for neurological function. We observed severe depletion of galactosylceramide and sulfatide in AD brain tissue, which can be traced metabolically to the loss of their biosynthetic precursor, very long chain ceramide. The synthesis of very long chain ceramides is catalyzed by ceramide synthase 2 (CERS2). We demonstrate a significant reduction in CERS2 activity as early as Braak stage I/II in temporal cortex, and Braak stage III/IV in hippocampus and frontal cortex, indicating that loss of myelin-specific ceramide synthase activity precedes neurofibrillary tangle pathology in cortical regions. These findings open a new vista on AD pathogenesis by demonstrating a defect in myelin lipid biosynthesis at the preclinical stages of the disease. We posit that, over time, this defect contributes significantly to myelin deterioration, synaptic dysfunction, and neurological decline. PMID- 27255819 TI - Braak stage and trajectory of cognitive decline in noncognitively impaired elders. AB - In a previous cross-sectional study, we found that nondemented elderly participants from the Rush Religious Orders Study (RROS) displayed a wide range of Braak neurofibrillary tangle and amyloid plaque pathology similar to that seen in prodromal and frank Alzheimer's disease. Here, we examined longitudinal changes in cognitive domains in subjects from this cohort grouped by Braak stage using linear mixed effects models. We found that the trajectory of episodic memory composite (EMC), executive function composite (EFC), and global cognitive composite scores (GCS: average of EMC and EFC scores) was significantly associated with age at visit over time, but not with Braak stage, apolipoprotein E (APOE) epsilon4 status or plaque pathology alone. By contrast, the combined effects of Braak stage, APOE status, and age at visit were strongly correlated with the trajectory of EMC, EFC and GCS performance over time. These data suggest that age and APOE epsilon4 status, rather than Alzheimer's disease-related pathology, play a more prominent role in the trajectory of cognitive decline over time in this elderly nondemented population. However, the findings reported require confirmation in a larger cohort of cases. PMID- 27255817 TI - Age-dependent differences in brain tissue microstructure assessed with neurite orientation dispersion and density imaging. AB - Human aging is accompanied by progressive changes in executive function and memory, but the biological mechanisms underlying these phenomena are not fully understood. Using neurite orientation dispersion and density imaging, we sought to examine the relationship between age, cellular microstructure, and neuropsychological scores in 116 late middle-aged, cognitively asymptomatic participants. Results revealed widespread increases in the volume fraction of isotropic diffusion and localized decreases in neurite density in frontal white matter regions with increasing age. In addition, several of these microstructural alterations were associated with poorer performance on tests of memory and executive function. These results suggest that neurite orientation dispersion and density imaging is capable of measuring age-related brain changes and the neural correlates of poorer performance on tests of cognitive functioning, largely in accordance with published histological findings and brain-imaging studies of people of this age range. Ultimately, this study sheds light on the processes underlying normal brain development in adulthood, knowledge that is critical for differentiating healthy aging from changes associated with dementia. PMID- 27255820 TI - Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats. AB - Advanced age is associated with a higher incidence of stroke and worse functional outcomes. Vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a potential method to improve recovery after brain injury but to date has only been evaluated in young rats. Here, we evaluated whether VNS paired with rehabilitative training would improve recovery of forelimb function after ischemic lesion of the motor cortex in rats 18 months of age. Rats were trained to perform the isometric pull task, an automated, quantitative measure of volitional forelimb strength. Once proficient, rats received an ischemic lesion of the motor cortex and underwent rehabilitative training paired with VNS for 6 weeks. VNS paired with rehabilitative training significantly enhances recovery of forelimb function after lesion. Rehabilitative training without VNS results in a 34% +/- 19% recovery, whereas VNS paired with rehabilitative training yields a 98% +/- 8% recovery of prelesion of forelimb function. VNS does not significantly reduce lesion size. These findings demonstrate that VNS paired with rehabilitative training enhances motor recovery in aged subjects in a model of stroke and may suggest that VNS therapy may effectively translate to elderly stroke patients. PMID- 27255821 TI - Concurrent white and gray matter degeneration of disease-specific networks in early-stage Alzheimer's disease and behavioral variant frontotemporal dementia. AB - This study investigates regional coherence between white matter (WM) microstructure and gray matter (GM) volume and perfusion measures in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) using a correlational approach. WM-GM coherence, compared with controls, was stronger between cingulum WM and frontotemporal GM in AD, and temporoparietal GM in bvFTD. In addition, in AD compared with controls, coherence was stronger between inferior fronto-occipital fasciculus WM microstructure and occipital GM perfusion. In this first study assessing regional WM-GM coherence in AD and bvFTD, we show that WM microstructure and GM volume and perfusion measures are coherent, particularly in regions implicated in AD and bvFTD pathology. This indicates concurrent degeneration in disease-specific networks. Our methodology allows for the detection of incipient abnormalities that go undetected in conventional between-group analyses. PMID- 27255822 TI - Perception-related EEG is more sensitive to Alzheimer's disease effects than resting EEG. AB - To characterize the effects of Alzheimer's disease (AD) on cortical functional connectivity in perception, we analyzed interhemispheric lagged synchronization (ILS) in the source space of high-density EEG recorded in aged controls and patients with amnestic mild cognitive impairment (aMCI) or AD while they viewed collinear and noncollinear bilateral moving gratings. Beta-band ILS was lower in aMCI and AD compared with controls in a large region centered on BA39. As previously reported, in young adults, collinear iso-oriented gratings versus noncollinear gratings synchronizes EEG reflecting perceptual grouping. Only aged controls showed the expected beta-band ILS increase originating in the dorsal visual stream (BA18). The aMCI group only showed a theta-band increase in an adjacent region (BA19). In AD patients, there was no ILS increase. Regression analysis revealed that the posterior callosal area and EEG slowing predict reduction of beta but not emergence of theta ILS response. Considering that we found no between-group differences in resting ILS, perception-related EEG appears to be more sensitive to AD effects, including ILS signs of neurodegeneration and compensation. PMID- 27255823 TI - The age-related neuroinflammatory environment promotes macrophage activation, which negatively impacts synaptic function. AB - The impact of infiltration of macrophages into the brain is debatable with evidence of both beneficial and detrimental effects. Recent work suggests that inflammatory macrophages, with an inflammatory phenotype that resembles the M1 activation state, may be detrimental, whereas anti-inflammatory M2-like macrophages may be beneficial. We set up a model to examine the response of bone marrow-derived macrophages to the inflammatory milieu that occurs in the aged brain. Expression of MHCII and CD40 was increased in macrophages incubated with soluble brain extract prepared from aged, compared with young, mice and this was accompanied by increased production of tumor necrosis factor-alpha and interleukin-6. Analysis of soluble brain extract indicated that it contained increased concentrations of several inflammatory mediators and, importantly, when bone marrow-derived macrophages were incubated in the inflammatory cytokines that were increased and applied to hippocampal slices, long-term potentiation was inhibited. The data suggest that infiltrating macrophages respond to local conditions and, in the case of aging, adopt an inflammatory phenotype that ultimately has a neurodetrimental effect. PMID- 27255824 TI - Determinants of iron accumulation in the normal aging brain. AB - In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p <= 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. PMID- 27255825 TI - Peripheral sphingolipids are associated with variation in white matter microstructure in older adults. AB - Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10.5 years later in 17 WM regions of 150 cognitively normal adults (mean age 67.2). Elevated ceramide species (C20:0, C22:0, C22:1, and C24:1) were associated with lower FA in multiple WM regions, including total cerebral WM, anterior corona radiata, and the cingulum of the cingulate gyrus. Higher sphingomyelins (C18:1 and C20:1) were associated with lower FA in regions such as the anterior corona radiata and body of the corpus callosum. Furthermore, lower sphingomyelin to ceramide ratios (C22:0, C24:0, and C24:1) were associated with lower FA or higher mean diffusivity in regions including the superior and posterior corona radiata. However, although these associations were significant at the a priori p < 0.05, only associations with some regional diffusion measures for ceramide C22:0 and sphingomyelin C18:1 survived correction for multiple comparisons. These findings suggest plasma sphingolipids are associated with variation in WM microstructure in cognitively normal aging. PMID- 27255826 TI - Tract-specific white matter microstructure and gait in humans. AB - Gait is a complex sequence of movements, requiring cooperation of many brain areas, such as the motor cortex, somatosensory cortex, and cerebellum. However, it is unclear which connecting white matter tracts are essential for communication across brain areas to facilitate proper gait. Using diffusion tensor imaging, we investigated associations of microstructural organization in 14 brain white matter tracts with gait, among 2330 dementia- and stroke-free community-dwelling individuals. Gait was assessed by electronic walkway and summarized into Global Gait, and 7 gait domains. Higher white matter microstructure associated with higher Global Gait, Phases, Variability, Pace, and Turning. Microstructure in thalamic radiations, followed by association tracts and the forceps major, associated most strongly with gait. Hence, in community dwelling individuals, higher white matter microstructure associated with better gait, including larger strides, more single support, less stride-to-stride variability, and less turning steps. Our findings suggest that intact thalamocortical communication, cortex-to-cortex communication, and interhemispheric visuospatial integration are most essential in human gait. PMID- 27255827 TI - Temporal discrimination threshold with healthy aging. AB - The temporal discrimination threshold (TDT) is the shortest interstimulus interval at which a subject can perceive successive stimuli as separate. To investigate the effects of aging on TDT, we studied tactile TDT using the method of limits with 120% of sensory threshold in each hand for each of 100 healthy volunteers, equally divided among men and women, across 10 age groups, from 18 to 79 years. Linear regression analysis showed that age was significantly related to left-hand mean, right-hand mean, and mean of 2 hands with R-square equal to 0.08, 0.164, and 0.132, respectively. Reliability analysis indicated that the 3 measures had fair-to-good reliability (intraclass correlation coefficient: 0.4 0.8). We conclude that TDT is affected by age and has fair-to-good reproducibility using our technique. PMID- 27255828 TI - Metabolic profiling of potential lung cancer biomarkers using bronchoalveolar lavage fluid and the integrated direct infusion/ gas chromatography mass spectrometry platform. AB - Lung cancer is one of the ten most common causes of death worldwide, so that the search for early diagnosis biomarkers is a very challenging task. Bronchoalveolar lavage fluid (BALF) provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomics techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. BIOLOGICAL SIGNIFICANCE: The search for early diagnosis of lung cancer is a very challenging task because of the high mortality associated to this disease and its critical linkage to the initiation of treatment. Bronchoalveolar lavage fluid provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Since BALF is in close interaction with lung tissue it is a more representative sample of lung status than other peripheral biofluids as blood or urine studied in previous works. Therefore, this study represents an innovative contribution in this topic that complement previous investigations about lung cancer, opening up new possibilities for understanding the pathogenesis of this disease and the use of efficient biomarkers. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomic techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically significant differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. PMID- 27255829 TI - Adult onset hemophagocytic lymphohistiocytosis prognosis is affected by underlying disease and coexisting viral infection: analysis of a single institution series of 35 patients. AB - Adult onset hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome, which can develop as a complication of many disorders. Early diagnosis is essential in order to avoid a fatal outcome. To confirm the diagnosis of acquired HLH made in a single institution series of adult patients with HLH-04 criteria, we applied the HScore and evaluated prognostic factors associated with clinical outcome. The median age of 35 patients was 54 (range 17-81), M/F ratio was 20/15. In 26/35 (74.3%) patients, an underlying haematological disease was present (2 Multicentric Castleman Disease, 10 B-cell Non-Hodgkin Lymphoma [NHL] and 14 T/NK-cell NHL); an autoimmune disorder was observed in four (11.4%) patients (one Still Disease, one undifferentiated connective tissue disease and two haemolytic anaemia); in five (14.3%), no underlying disease was identified. A concomitant infection by EBV was observed in 10 patients (28.6%), CMV in 8 (22.9%), HHV8 in 6 (17.1%) and HIV in 1 (2.9%). Hyperferritinemia, fever and splenomegaly were present in more than 90% of patients, whereas bone marrow hemophagocytosis in 51% of cases only. According to HScore, 34/35 patients had a >75% and 32/35 >93% probability of HLH. Four-year overall survival and HLH-free survival were 17.8% (CI 1.9-33.8) and 23.8% (CI 7.3-40.3), respectively. By multivariate analysis, presence of oedema and hyperbilirubinemia were predictors of death, whereas there was a statistically significant trend for viral infection as predictor of poor prognosis. B-NHL diagnosis was confirmed as associated to a better prognosis in comparison with T/NK lymphoma (4-year HFS 53.3% vs. 0%, p = 0.09) and similar to other aetiologies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27255830 TI - Medications associated with geriatric syndromes and their prevalence in older hospitalized adults discharged to skilled nursing facilities. AB - BACKGROUND: More than half of the hospitalized older adults discharged to skilled nursing facilities (SNFs) have more than 3 geriatric syndromes. Pharmacotherapy may be contributing to geriatric syndromes in this population. OBJECTIVES: Develop a list of medications associated with geriatric syndromes and describe their prevalence in patients discharged from acute care to SNFs. DESIGN: Literature review and multidisciplinary expert panel discussion, followed by cross-sectional analysis. SETTING: Academic medical center in the United States PARTICIPANTS: One hundred fifty-four hospitalized Medicare beneficiaries discharged to SNFs. MEASUREMENTS: Development of a list of medications that are associated with 6 geriatric syndromes. Prevalence of the medications associated with geriatric syndromes was examined in the hospital discharge sample. RESULTS: A list of 513 medications was developed as potentially contributing to 6 geriatric syndromes: cognitive impairment, delirium, falls, reduced appetite or weight loss, urinary incontinence, and depression. Medications included 18 categories. Antiepileptics were associated with all syndromes, whereas antipsychotics, antidepressants, antiparkinsonism, and opioid agonists were associated with 5 geriatric syndromes. In the prevalence sample, patients were discharged to SNFs with an overall average of 14.0 (+/-4.7) medications, including an average of 5.9 (+/-2.2) medications that could contribute to geriatric syndromes, with falls having the most associated medications at discharge at 5.5 (+/-2.2). CONCLUSIONS: Many commonly prescribed medications are associated with geriatric syndromes. Over 40% of all medications ordered upon discharge to SNFs were associated with geriatric syndromes and could be contributing to the high prevalence of geriatric syndromes experienced by this population. Journal of Hospital Medicine 2016;11:694-700. (c) 2016 Society of Hospital Medicine. PMID- 27255831 TI - Influence of HIV infection and the use of antiretroviral therapy on selenium and selenomethionine concentrations and antioxidant protection. AB - OBJECTIVE: The aim of the present study was to evaluate whether HIV infection and antiretroviral therapy (ART) use are associated with oxidative stress, concentrations of selenium and selenomethionine, and antioxidant protection. METHODS: Individuals were classified as HIV negatives: control group (CG; n = 40); HIV positives: group 1 (G1; taking ART for >5 y, n = 40) and group 2 (G2; taking ART for <5 y, n = 40). Plasma and erythrocyte selenium, selenomethionine, glutathione (GSH), glutathione peroxidase activity (GPX), and malondialdehyde (MDA) were evaluated. RESULTS: Selenium deficiency (plasma selenium 45 MUg/L) was not observed in any of the participants, and plasma selenium in CG (69.4 MUg/L) was lower than in G1 and G2 (88.4 and 72.5 MUg/L, respectively). G1 and G2 showed higher concentrations of MDA and GPX and lower concentration of GSH than CG. Multiple linear regression analysis indicated an association of MDA, GPX, and GSH with HIV status. CG participants showed higher concentrations of selenomethionine than G1 and G2 individuals and we observed a significant negative correlation between the concentration of selenomethionine and the use of ART. CONCLUSIONS: Prolonged ART use seems to increase the selenium in plasma, but influences the reduction of selenomethionine. HIV infection was associated with increased oxidative stress and appears to affect in protective activity of GPX. Finally, more studies are required to further address the importance of selenium and selenometabolites in the pathogenesis of infection and metabolism of HIV-positive individuals in prolonged use of ART. PMID- 27255832 TI - Pro-apoptotic Bax molecules densely populate the edges of membrane pores. AB - How the pro-apoptotic Bax protein permeabilizes the mitochondrial outer membrane is not fully understood. Previously, using cryo-electron microscopy (cryo-EM), we showed that activated Bax forms large, growing pores. Whether formed in liposomes or in mitochondrial outer membranes, Bax-induced pores exhibit the same morphology, with negative curvature flanking the edges and with no visible protein structure protruding from the membranes. Here we used cryo-EM to show that gold-labeled Bax molecules, after activation by Bid, became localized strictly at pore edges. This argues that Bax acts at short range to deform the membrane. Also, Bax molecules populated the walls of both small and large pores at the same density, implying that Bax is continuously recruited to the pores as they widen. Moreover, because all Bax molecules became oligomerized after membrane insertion, we infer that Bax oligomers are present at pore edges. We suggest that oligomerization may promote pore enlargement. PMID- 27255833 TI - Long-term potentiation-like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset. AB - OBJECTIVE: Alzheimer's disease (AD) is considered an age-related disorder. However, it is unclear whether AD induces the same pathological and neurophysiological modifications in synaptic functions independently from age of disease onset. We used transcranial magnetic stimulation tools to investigate the mechanisms of cortical plasticity and sensory-motor integration in AD patients with a wide range of disease onset. METHODS: We evaluated newly diagnosed sporadic AD (n = 54) in comparison with healthy age-matched controls (HS; n = 24). Cortical plasticity mechanisms of long-term potentiation (LTP) or of long term depression (LTD) were assessed using respectively intermittent (iTBS) or continuous theta burst stimulation (cTBS) protocols. Sensory-motor integration was evaluated by means of short afferent inhibition (SAI) protocol. RESULTS: AD patients show after iTBS an impairment of LTP-like cortical plasticity forming a paradoxical LTD in comparison to HS. LTD-like cortical plasticity is similar between AD and HS. LTP-like cortical plasticity is not associated with age, but AD patients presenting with more altered LTP-like cortical plasticity have more severe cognitive decline at 18 months. SAI is impaired in AD and shows a strong association with the individual age of subjects rather than with disease age of onset. INTERPRETATION: Cortical LTP disruption is a central mechanism of AD that is independent from age of onset. AD can be described primarily as a disorder of LTP-like cortical plasticity not influenced by physiological aging and associated with a more-severe cognitive decline. Ann Neurol 2016;80:202-210. PMID- 27255834 TI - Role of bifunctional ammonia-lyase in grass cell wall biosynthesis. AB - L-Phenylalanine ammonia-lyase (PAL) is the first enzyme in the biosynthesis of phenylpropanoid-derived plant compounds such as flavonoids, coumarins and the cell wall polymer lignin. The cell walls of grasses possess higher proportions of syringyl (S)-rich lignins and high levels of esterified coumaric acid compared with those of dicotyledonous plants, and PAL from grasses can also possess tyrosine ammonia-lyase (TAL) activity, the reason for which has remained unclear. Using phylogenetic, transcriptomic and in vitro biochemical analyses, we identified a single homotetrameric bifunctional ammonia-lyase (PTAL) among eight BdPAL enzymes in the model grass species Brachypodium distachyon. (13)C isotope labelling experiments along with BdPTAL1-downregulation in transgenic plants showed that the TAL activity of BdPTAL1 can provide nearly half of the total lignin deposited in Brachypodium, with a preference for S-lignin and wall-bound coumarate biosynthesis, indicating that PTAL function is linked to the characteristic features of grass cell walls. Furthermore, isotope dilution experiments suggest that the pathways to lignin from L-phenylalanine and L tyrosine are distinct beyond the formation of 4-coumarate, supporting the organization of lignin synthesis enzymes in one or more metabolons. PMID- 27255835 TI - Convergence of light and chloroplast signals for de-etiolation through ABI4-HY5 and COP1. AB - Seedling de-etiolation prepares plants to switch from heterotrophic to photoautotrophic growth, a transition essential for plant survival. This delicate de-etiolation process is precisely controlled by environmental and endogenous signals. Although intracellular plastid-derived retrograde signalling is essential for the de-etiolation process, the molecular nature of these retrograde signals remains elusive(1-3). Here we show that chloroplast and light signals antagonistically fine-tune a suite of developmental and physiological responses associated with de-etiolation through a transcriptional module of ABA INSENSITIVE 4 (ABI4) and ELONGATED HYPOCOTYL 5 (HY5). Moreover, ABI4 and HY5 antagonistically regulate the expression of CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) and the subsequent greening process. In turn, ABI4 and HY5 are targeted for degradation by COP1 in the light and dark, respectively, to ensure a proper interplay of ABI4 and HY5 actions during seedling de-etiolation. Our study provides a new molecular mechanism for understanding how chloroplast signals converge with light signals to optimize early plant development. PMID- 27255836 TI - Hydraulic basis for the evolution of photosynthetic productivity. AB - Clarifying the evolution and mechanisms for photosynthetic productivity is a key to both improving crops and understanding plant evolution and habitat distributions. Current theory recognizes a role for the hydraulics of water transport as a potential determinant of photosynthetic productivity based on comparative data across disparate species. However, there has never been rigorous support for the maintenance of this relationship during an evolutionary radiation. We tested this theory for 30 species of Viburnum, diverse in leaf shape and photosynthetic anatomy, grown in a common garden. We found strong support for a fundamental requirement for leaf hydraulic capacity (Kleaf) in determining photosynthetic capacity (Amax), as these traits diversified across this lineage in tight coordination, with their proportionality modulated by the climate experienced in the species' range. Variation in Kleaf arose from differences in venation architecture that influenced xylem and especially outside xylem flow pathways. These findings substantiate an evolutionary basis for the coordination of hydraulic and photosynthetic physiology across species, and their co-dependence on climate, establishing a fundamental role for water transport in the evolution of the photosynthetic rate. PMID- 27255837 TI - The rubber tree genome reveals new insights into rubber production and species adaptation. AB - The Para rubber tree (Hevea brasiliensis) is an economically important tropical tree species that produces natural rubber, an essential industrial raw material. Here we present a high-quality genome assembly of this species (1.37 Gb, scaffold N50 = 1.28 Mb) that covers 93.8% of the genome (1.47 Gb) and harbours 43,792 predicted protein-coding genes. A striking expansion of the REF/SRPP (rubber elongation factor/small rubber particle protein) gene family and its divergence into several laticifer-specific isoforms seem crucial for rubber biosynthesis. The REF/SRPP family has isoforms with sizes similar to or larger than SRPP1 (204 amino acids) in 17 other plants examined, but no isoforms with similar sizes to REF1 (138 amino acids), the predominant molecular variant. A pivotal point in Hevea evolution was the emergence of REF1, which is located on the surface of large rubber particles that account for 93% of rubber in the latex (despite constituting only 6% of total rubber particles, large and small). The stringent control of ethylene synthesis under active ethylene signalling and response in laticifers resolves a longstanding mystery of ethylene stimulation in rubber production. Our study, which includes the re-sequencing of five other Hevea cultivars and extensive RNA-seq data, provides a valuable resource for functional genomics and tools for breeding elite Hevea cultivars. PMID- 27255839 TI - NaKR1 regulates long-distance movement of FLOWERING LOCUS T in Arabidopsis. AB - Flowering plants perceive photoperiodic signals in leaves to generate mobile stimuli required for the induction of flower formation at shoot apices. Although FLOWERING LOCUS T (FT) has been identified as part of the mobile floral stimuli in Arabidopsis thaliana, the mechanisms underlying long-distance movement of FT from leaves to shoot apices remain largely unclear. Here we show that a heavy metal-associated (HMA) domain-containing protein, SODIUM POTASSIUM ROOT DEFECTIVE 1 (NaKR1), is activated by CONSTANS (CO) under long-day conditions and regulates long-distance movement of FT in Arabidopsis. Loss of function of NaKR1 compromises FT transport to shoot apices through sieve elements, causing late flowering under long-day conditions. NaKR1 and FT share similar expression patterns and subcellular localization, and interact with each other in vivo. Grafting experiments demonstrate that NaKR1 promotes flowering through mediating FT translocation from leaves to shoot apices. Thus, photoperiodic control of floral induction requires NaKR1-mediated long-distance delivery of florigenic signals. PMID- 27255840 TI - Challenges of transgenic crop commercialization in China. PMID- 27255838 TI - Insight into the evolution of the Solanaceae from the parental genomes of Petunia hybrida. AB - Petunia hybrida is a popular bedding plant that has a long history as a genetic model system. We report the whole-genome sequencing and assembly of inbred derivatives of its two wild parents, P. axillaris N and P. inflata S6. The assemblies include 91.3% and 90.2% coverage of their diploid genomes (1.4 Gb; 2n = 14) containing 32,928 and 36,697 protein-coding genes, respectively. The genomes reveal that the Petunia lineage has experienced at least two rounds of hexaploidization: the older gamma event, which is shared with most Eudicots, and a more recent Solanaceae event that is shared with tomato and other solanaceous species. Transcription factors involved in the shift from bee to moth pollination reside in particularly dynamic regions of the genome, which may have been key to the remarkable diversity of floral colour patterns and pollination systems. The high-quality genome sequences will enhance the value of Petunia as a model system for research on unique biological phenomena such as small RNAs, symbiosis, self incompatibility and circadian rhythms. PMID- 27255841 TI - The essential need for GM crops. PMID- 27255842 TI - Archaeobotany: The wheat and the chaff. PMID- 27255843 TI - Lignin biosynthesis: Tyrosine shortcut in grasses. PMID- 27255844 TI - Flowering time: Have florigen, will travel. PMID- 27255846 TI - Ethnogenomics: The societies that rubber built. PMID- 27255845 TI - Secrets of the world's most popular bedding plant unlocked. PMID- 27255847 TI - Gorilla behaviour: Audible enjoyment. PMID- 27255848 TI - Meristem development: Ratchet block. PMID- 27255849 TI - Auxin signalling: Grass on acid. PMID- 27255850 TI - Floral scent: Extending encounters. PMID- 27255851 TI - Strength in shoulders. PMID- 27255852 TI - Stopping Manual and Vocal Actions in Tourette's Syndrome. AB - Evidence that Tourette's syndrome (TS) disrupts inhibitory motor control is highly mixed. The authors investigated inhibitory control of manual and vocal actions in young adults with relatively uncomplicated, persistent TS. Both TS and control groups showed similar response latencies when executing manual and vocal reactions, but individuals with TS were slower at stopping their manual and vocal responses. While alterations in inhibitory motor control may not be a generalizable phenomenon in TS, these results add to an emerging literature suggesting that individuals with relatively uncomplicated TS, whose symptoms persist into adulthood, show disruption to inhibitory control mechanisms. PMID- 27255853 TI - Remote Cerebellar Stroke Associated With Delusions and Disorganization. PMID- 27255854 TI - White Matter Dementia: Origin, Development, Progress, and Prospects. AB - The term white matter dementia (WMD) was introduced in 1988 to highlight the role of white matter in the development of dementia. As the concept has been refined with new insights into the structure and function of normal and abnormal white matter, research has expanded to consider normal cognition, network connectivity, novel treatment ideas, and the etiopathogenesis of neurodegenerative dementia. Emerging data are also identifying new opportunities for dementia prevention by avoidance of acquired vascular and traumatic white matter insults. The idea of WMD promises to continue as a useful construct informing the study of dementia and the understanding of brain-behavior relationships. PMID- 27255855 TI - Depression Symptoms in Chronic Left Hemisphere Stroke Are Related to Dorsolateral Prefrontal Cortex Damage. AB - Damage to the brain's mood regulation systems may contribute to poststroke depression. This study examines relationships between depression symptoms and psychosocial factors and then uses multivariate lesion-symptom mapping to localize depression symptoms in people with chronic left hemisphere stroke. Depression symptoms relate inversely to education and directly to physical disability. Damage in the left dorsolateral prefrontal cortex is associated with greater depression symptoms. These results demonstrate a neurological contribution to depression symptoms in chronic left hemisphere stroke and provide evidence of convergent biological mechanisms for poststroke depression symptoms and major depression with regard to left dorsolateral prefrontal cortex dysfunction. PMID- 27255856 TI - Screening for Cognitive Impairments After Traumatic Brain Injury: A Comparison of a Brief Computerized Battery With the Montreal Cognitive Assessment. AB - Detecting cognitive dysfunction in a busy traumatic brain injury (TBI) clinic is challenging given the length of conventional assessments and the need for psychometric expertise. The authors report the utility of a 10-minute, easily administered computerized battery that is more sensitive than the Montreal Cognitive Assessment in detecting cognitive impairments in people with a TBI. PMID- 27255857 TI - Amygdala Volumetric Change Following Psychotherapy for Posttraumatic Stress Disorder. AB - The authors investigated the impact of eye movement desensitization and reprocessing (EMDR) and prolonged exposure (PE) on the volumes of the amygdala and hippocampus, structures known to be important in fear conditioning, in 20 patients with posttraumatic stress disorder (PTSD). Patients were randomly allocated to either EMDR or PE. Volumes were assessed before and after treatment via magnetic resonance imaging (MRI). Both groups showed significant improvements in PTSD symptoms. Left amygdala mean volume increased significantly following EMDR treatment only. No significant volumetric changes were found for the hippocampus. PMID- 27255858 TI - Evaluation of a New Newborn Screening Model for Cystic Fibrosis. PMID- 27255859 TI - Count on It! Accurately Measured Respiratory Rate Is Associated with Lung Function and Clinical Severity in Children with Acute Asthma Exacerbations. PMID- 27255860 TI - Fetal, neonatal, and infant microbiome: Perturbations and subsequent effects on brain development and behavior. AB - The human gastrointestinal tract harbors a diverse and complex community of microbes, termed gut microbiota, that normally assemble during the first postnatal years of life. This evolution-driven process has been shown to contribute to the developmental programming of epithelial barrier function, gut homeostasis, and angiogenesis, as well as the development and function of the immune system. Research over the last few years has revealed that the actions of the gut microbiota have much wider effects on host physiology and development than originally believed, including the modulation of brain development and behavior. This article briefly reviews recent findings on the impact of the gut microbiota on brain development, and how disturbances in the assembly and maturation of the gut microbiota may impact development of motor, social, and cognitive functions. The potential link between microbiota and metabolic requirements of the developing brain is also considered. PMID- 27255861 TI - Genetic evidence for involvement of membrane trafficking in the action of 5 fluorouracil. AB - To identify novel genes that mediate cellular sensitivity and resistance to 5 fluorouracil (5-FU), we performed a genome-wide genetic screening to identify altered susceptibility to 5-FU by Schizosaccharomyces pombe haploid nonessential gene deletion library containing 3004 deletion mutants. We identified 50 hypersensitive and 12 resistant mutants to this drug. Mutants sensitive or resistant to 5-FU were classified into various categories based on their putative functions. The largest group of the genes whose disruption renders cells altered susceptibility to 5-FU is involved in nucleic acid metabolism, but to our surprise, the second largest group is involved in membrane trafficking. In addition, several other membrane traffic mutants examined including gdi1-i11, ypt3-i5, Deltaryh1, Deltaric1, and Deltaaps1 exhibited hypersensitivity to 5-FU. Furthermore, we found that 5-FU in low concentration that generally do not affect cell growth altered the localization of Syb1, a secretory vesicle SNARE synaptobrevin which is cycled between the plasma membrane and the endocytic pathway. Notably, 5-FU at such low concentration also significantly inhibited the secretion of acid phosphatase. Altogether, our findings revealed the first evidence that 5-FU influences membrane trafficking as the potential underlying mechanism of the drug action. PMID- 27255862 TI - The Potential Impact of Internet and Mobile Use on Headache and Other Somatic Symptoms in Adolescence. A Population-Based Cross-Sectional Study. AB - OBJECTIVE: The purpose of this cross-sectional study was to determine whether migraine or tension-type headaches are associated with abuse of the internet and/or mobile phones and to explore whether headache and the abuse of the two technologies are associated with sleep disturbances and other self-reported somatic symptoms. BACKGROUND: In the last several years, estimates indicate the increasing pervasiveness of the internet and other technologies in the lives of young people, highlighting the impact on well-being. DESIGN: A population-based cross-sectional study was conducted between February 2013 and June 2014. METHOD: The initial sample was composed of 1004 Italian students (aged 10-16 years) recruited within public middle schools not randomly selected in central Italy. The final convenience sample consisted of 841 students (Males = 51.1%; Females = 48.9%) who were included in the analysis. Data were collected using self-reported measures. RESULTS: Headache was reported by 28.0% of the total sample. A significant relationship was determined with gender (chi(2) (1) = 7.78, P < .01), with female students being overrepresented in the headache group. Approximately 39.6% of subjects were non-abusers of both technologies, internet and mobile. Mobile only abusers were approximately 26.0% of the study population; internet only abusers were approximately 14.9%; and abusers of both media were 19.5%. No significant relationship was found between students with and without headache with respect to the abuse of internet and mobile phone categories (headache was, respectively, the 26% in no abusers, the 30% in internet abusers, the 29% in mobile abusers, and the 29% in internet and mobile abusers, P = .86). Additionally, also by excluding the no headache group, the relationship between the two groups of headache (migraine and tension type headache) and the abuse of media (tension type headache was the 31% in no abusers, the 43% in internet abusers, the 49% in mobile abusers, and the 29% in internet and mobile abusers) is not statistically significant (P = .06). No significant relationship emerged between headache and the internet and mobile phone addiction groups (headache was the 28% in no addiction group, the 35% in mobile addiction group, the 25% of internet addiction group, and the 28% in mobile and internet addiction group, P = .57) as well as no significant relationship was found when only the different headache types were considered (tension type headache was the 39% in no addiction group, the 40% in mobile addiction group, the 32% in internet addiction group, and the 31% in mobile and internet addiction group, P = .71). Daily internet users reported higher median scores for somatic symptoms than the occasional internet users in the no-headache group (Kruskal-Wallis chi(2) (1) = 5.44, P = .02) and in the migraine group (Kruskal-Wallis chi(2) (1) = 6.54, P = .01). CONCLUSIONS: Results highlighted the potential impact of excessive internet and mobile use, which ranges from different types of headache to other somatic symptoms. Further studies are needed to confirm these findings and to determine if there is a need for promoting preventive health interventions, especially in school setting. PMID- 27255864 TI - How differences matter: tracing diversity practices in obesity treatment and health promotion. AB - Diversity has become a buzzword in medical care, denoting a re-evaluation of what it means to attend to differences among human bodies and lives. Questions about what types of differences matter and how they should be defined have become important normative and analytical challenges. Drawing on two case studies, we show how differences between patients and patient-collectives are not simply waiting to be recognised and addressed but also enacted within situated healthcare practices. Although concerns with diversity are present in both cases, they take different forms. In a Viennese health-promotion project for obese clients, care practices are both based on and reproduce large-scale categories that divide the population into distinct subgroups with specific needs. Conversely, in an outpatient clinic for bariatric surgery patients, a technical fix-oriented procedure leads to concerns over diversity becoming an add-on realised by tending to each patient's idiosyncrasies and personal stories. By tracing the practices of diversity and the tensions they produce, we show how classifications and understandings of human difference are based on infrastructures that enable and constrain them. Furthermore, we discuss how they become consequential in healthcare, thereby indicating the importance of remaining reflexive about the political implications of diversity discourse and practice. PMID- 27255865 TI - Epidermal electronics for electromyography: An application to swallowing therapy. AB - Head and neck cancer treatment alters the anatomy and physiology of patients. Resulting swallowing difficulties can lead to serious health concerns. Surface electromyography (sEMG) is used as an adjuvant to swallowing therapy exercises. sEMG signal collected from the area under the chin provides visual biofeedback from muscle contractions and is used to help patients perform exercises correctly. However, conventional sEMG adhesive pads are relatively thick and difficult to effectively adhere to a patient's altered chin anatomy, potentially leading to poor signal acquisition in this population. Here, the emerging technology of epidermal electronics is introduced, where ultra-thin geometry allows for close contouring of the chin. The two objectives of this study were to (1) assess the potential of epidermal electronics technology for use with swallowing therapy and (2) assess the significance of the reference electrode placement. This study showed comparative signals between the new epidermal sEMG patch and the conventional adhesive patches used by clinicians. Furthermore, an integrated reference yielded optimal signal for clinical use; this configuration was more robust to head movements than when an external reference was used. Improvements for future iterations of epidermal sEMG patches specific to day-to day clinical use are suggested. PMID- 27255867 TI - A 58-Year-Old Man With Self-Inflicted Facial Trauma. PMID- 27255868 TI - Chest Pain. PMID- 27255869 TI - Loss of Opportunity. PMID- 27255872 TI - 2015 Air Medical Safety Survey. PMID- 27255863 TI - Challenges in structural approaches to cell modeling. AB - Computational modeling is essential for structural characterization of biomolecular mechanisms across the broad spectrum of scales. Adequate understanding of biomolecular mechanisms inherently involves our ability to model them. Structural modeling of individual biomolecules and their interactions has been rapidly progressing. However, in terms of the broader picture, the focus is shifting toward larger systems, up to the level of a cell. Such modeling involves a more dynamic and realistic representation of the interactomes in vivo, in a crowded cellular environment, as well as membranes and membrane proteins, and other cellular components. Structural modeling of a cell complements computational approaches to cellular mechanisms based on differential equations, graph models, and other techniques to model biological networks, imaging data, etc. Structural modeling along with other computational and experimental approaches will provide a fundamental understanding of life at the molecular level and lead to important applications to biology and medicine. A cross section of diverse approaches presented in this review illustrates the developing shift from the structural modeling of individual molecules to that of cell biology. Studies in several related areas are covered: biological networks; automated construction of three-dimensional cell models using experimental data; modeling of protein complexes; prediction of non-specific and transient protein interactions; thermodynamic and kinetic effects of crowding; cellular membrane modeling; and modeling of chromosomes. The review presents an expert opinion on the current state-of-the-art in these various aspects of structural modeling in cellular biology, and the prospects of future developments in this emerging field. PMID- 27255873 TI - Implementing a Neonatal Transport System With Simulation in Kosovo. AB - OBJECTIVE: Post-war Kosovar health care systems have reduced gaps in maternal and newborn health care. Coordinated neonatal transport programs may further improve survival and morbidities. METHODS: Transport care paradigms were tested using in situ (Kosovo) and ex situ (the United States) mobile immersive simulation. Patient demographics and outcomes were measured at the tertiary referral center. RESULTS: Four paired physician and nurse transport teams performed 7 simulated interfacility transports across Kosovo. In situ simulations revealed safety threats in facilities, ambulances, and team process. Ex situ observations reinforced roles and professionalism. For the first year after simulations, tertiary neonatal intensive care unit admissions were more premature (-2.4 weeks), smaller (-725 g), and out born (+12%). Mortality was higher (14.7% vs. 7.8%), hypothermia was lower (0.2% vs. 4.6%), and culture-positive sepsis was lower (15.7% vs. 42.9%). CONCLUSION: In situ augmented by ex situ simulation provided perspective and depth of understanding to implement a new care delivery paradigm. Simulations involving Kosovar health care providers across a network of facilities generated practical experience in nationwide neonatal transport, with temporal association to altered referral patterns at the tertiary care facility. PMID- 27255874 TI - Intubation Performance of Advanced Airway Devices in a Helicopter Emergency Medical Service Setting. AB - OBJECTIVE: This study attempts to determine if newer indirect laryngoscopes or intubating devices are superior to a standard laryngoscope for intubation success among helicopter emergency medical service (HEMS) personnel. METHODS: Flight nurses and paramedics intubated standardized mannequins with a normal airway, a trauma airway, and a difficult airway using a standard laryngoscope, a gum elastic bougie, the Airtraq laryngoscope (King System Corp, Noblesville, IN), the Glidescope Ranger laryngoscope (Verathon Inc, Bothell, WA), and the S.A.L.T. device (Microtek Medical, Inc, Lehmberg, IN) in grounded helicopters wearing helmets and flight gear. Participant demographics, time to glottic view, the modified Cormack-Lehane score, total intubation time, number of attempts, and overall successful intubation were recorded for each type of airway. RESULTS: Two hundred thirty-six subjects were initially enrolled across 107 bases in 15 states, and 177 completed the study. First-attempt success rates did not vary by device for the normal airway (P = .203), but the Airtraq laryngoscope and the S.A.L.T. device were highest in the difficult airway (82.0% and 85.0%, respectively; P < .0001). The time to first-attempt success in the difficult airway was lowest for the S.A.L.T. device and the Airtraq laryngoscope (mean = 9.72 seconds and 19.70 seconds, respectively; P < .0001). CONCLUSION: Using HEMS providers, the Airtraq laryngoscope and the S.A.L.T. device showed the fastest and highest intubation success on the first attempt in difficult simulated HEMS airway scenarios. PMID- 27255876 TI - Structure of Rapid Response Car Operations in an Urban Trauma Service. AB - OBJECTIVE: Emergency medical vehicle collisions are an inherent risk for health care providers, patients, and other road users. Air ambulance services often use rapid response cars (RRCs) to maintain operational resilience. We aim to describe the operational concept of London's Air Ambulance (LAA) RRCs and activity over a 1-year period. METHODS: This was a retrospective dispatch database study. The RRC operational concept, car configuration, and training are also described. RESULTS: LAA implemented principles from motorsports and aviation including car configuration, training, navigation, and communication. RRCs were activated a total of 2,241 times during the study period (average of 6.1 activations per day). RRCs traveled a total of 22,973 km and a median of 8.7 km (interquartile range = 5-15.1) with blue lights; there were missing data for 123 (5%) activations. Furthermore, the RRCs spent a total of 28,536 minutes with blue lights and a median of 12 minutes (interquartile range = 7-18); there were missing data for 89 (4%) activations. The safety management system included 5 reports, none of which were related to serious RRC incidents. CONCLUSION: Translating lessons from aviation and motorsports, LAA has developed an RRC operation concept to improve safety and operational capacity. One-year operational data indicate high activity without any serious incidents. PMID- 27255875 TI - Airway Management: A Structured Curriculum for Critical Care Transport Providers. AB - OBJECTIVE: Airway assessment and management are vital skills for the critical care transport provider. Nurses and paramedics often enter a transport program with limited or no exposure to airway management. Many programs lack a structured curriculum to show skill competence. Optimal methods in the development of airway management competence and the frequency of training needed to maintain skills have not been clearly defined. Because of this lack of standardization, the actual level of competence in both new and experienced critical care transport providers is unknown. METHODS: A pretest, post-test repeated measures approach using an online curriculum combined with a deliberate practice model was used. Competence in airway management was measured using 3 evaluation points: static mannequin head, simulation scenario, and the live patient. RESULTS: A convenience sample of critical care transport providers participated (N = 9). Knowledge improvement was significant, with a higher percentage of participants scoring above 85% on the post-test compared with the pretest (P = .028). Mean scores in completion of the airway checklist pre- versus postintervention were significantly increased on all 3 evaluation points (P < .001 for all comparisons). Significant changes were noted in the response profile evaluating participants' confidence in their ability to verbalize indications for endotracheal intubation (P < .05). CONCLUSION: The development of a standardized, blended learning curriculum combined with deliberate simulation practice and rigorous assessment showed improvements in multiple areas of airway assessment and management. PMID- 27255877 TI - Emergent Bleeding in Patients Receiving Direct Oral Anticoagulants. AB - Direct oral anticoagulants (DOACs) offer clinical advantages over warfarin, such as minimal medication and food interactions and fixed dosing without the need for routine monitoring of coagulation status. As with all anticoagulants, bleeding, either spontaneous or provoked, is the most common complication. The long-term use of these drugs is increasing, and there is a crucial need for emergency medicine service professionals to understand the optimal management of associated bleeding. This review aims to describe the indications and pharmacokinetics of available DOACs; to discuss the risk of bleeding; to provide a treatment algorithm to manage DOAC-associated emergency bleeding; and to discuss future directions in bleeding management, including the role of specific reversal agents, such as the recently approved idarucizumab for reversal of the direct thrombin inhibitor dabigatran. Because air medical personnel are increasingly likely to encounter patients receiving DOACs, it is important that they have an understanding of how to manage patients with emergent bleeding. PMID- 27255878 TI - Cerebral Oxygenation and Acceleration in Pediatric and Neonatal Interfacility Transport. AB - OBJECTIVE: The purpose of this study is to measure peak acceleration forces during interfacility transport; examine whether drops in cerebral oxygenation occurred; and test the associations between cerebral oxygenation, acceleration, and patient positioning. METHODS: A cerebral oximeter (INVOS-5100C; Somanetics, Minneapolis, MN) monitored regional saturation of oxygen (rSO2 [cerebral oxygenation]) in pediatric and neonatal patients (N = 24) transported between facilities by ground ambulance, helicopter, or fixed wing aircraft. An accelerometer (GP1; SENSR, Georgetown, TX) bolted to the isolette or gurney recorded z-axis (aligned with the spine) accelerations. RESULTS: The z-axis peak accelerations (absolute values of g) by transport type were as follows: ground ambulance takeoff mean = 0.16 and landing mean = 0.08, helicopter takeoff mean = 0.16 and landing mean = 0.05, fixed wing aircraft takeoff mean = 0.14 and landing mean = 0.20. During takeoff, 2 of 7 patients in the head-to-front of vehicle position experienced rSO2 drop. During landing, 4 of 13 patients in the head-to back of vehicle position experienced rSO2 drop. There were no significant associations of rSO2 drop during takeoff and landing with patient positioning or with z-axis peak acceleration. CONCLUSION: Acceleration forces of pediatric and neonatal interfacility transport are small and comparable in magnitude. The relationship between rSO2 drop and patient positioning was not significant in this pilot study. PMID- 27255879 TI - Mechanical Ventilation in Critical Care Transport. AB - OBJECTIVE: Although the benefit of transferring patients with hypoxemic respiratory failure to tertiary care centers has been shown, transporting hypoxemic patients remains controversial, given the risk of desaturation in transit. METHODS: We performed a retrospective analysis of a database of critical care transports (CCTs) of patients with hypoxemic respiratory failure to quantify the number, types, and effects of ventilator changes performed by the CCT teams. We evaluated the changes in fraction of inspired oxygen (FiO2), positive end expiratory pressure (PEEP), tidal volume, both FiO2 and PEEP, and the administration of a neuromuscular blocking medication to assess for an association with an improvement in the arterial partial pressure of oxygen (PaO2) from the sending to the receiving hospitals. RESULTS: Ventilator changes were made in 211 (89%) of the 237 identified transports, with significant changes in the tidal volume, PEEP, and FiO2. Analysis of variance revealed a significant relationship between changes in FiO2, PEEP, tidal volume, FiO2 and PEEP, and the administration of neuromuscular blocking agents and change in PaO2 (F5,1037 = 119.6, P < .001). Multivariable regression analyses showed a significant association between an increase in PaO2 and increasing FiO2, increasing FiO2 and PEEP, and the administration of a neuromuscular blocking medication. CONCLUSION: The CCT team performed multiple changes to ventilators. Complex ventilator management was associated with a higher PaO2 on arrival. PMID- 27255880 TI - Drowning Injuries: Analysis of a Decennial Air Medical Rescue Center Experience. AB - OBJECTIVE: Drowning is one of the leading injury death causes in younger children. Common intensive care measures seem not to improve neurologic outcome, and early prognostic options appear partially unreliable. Therefore, we evaluated a cohort of drowning patients cotreated by a helicopter emergency medical service regarding typical incident constellations, early and subsequent prognostic options, and relevant interventions. METHODS: All patients prehospitally cotreated by helicopter emergency medical service "Christoph 4" in primary missions because of drowning incidents during a 10-year period were evaluated. Patient, prehospital, and clinical data were recorded retrospectively; correlations and prognostic values were evaluated with appropriate statistical tests. RESULTS: Fifty-one patients were included. Various examination results (several vital, neurologic, and laboratory parameters) and sufficient prehospital first aid measures were significantly correlated with the final outcome (P < .05, respectively). Aspartate aminotransferase and alanine aminotransferase values precisely discriminated between the final outcome groups (P = .001 and area under the receiver operating characteristic curve = 1.0 in both cases). CONCLUSION: Aspartate aminotransferase and alanine aminotransferase values were the most useful predictors of outcome in our study. Sufficient prehospital first aid measures were correlated with improved outcome. Regular first aider training is recommended. PMID- 27255881 TI - Pediatric Extracorporeal Membrane Oxygenation Transport by EC-145 With a Custom Built Sled. AB - Indications for the use of extracorporeal membrane oxygenation (ECMO) in pediatrics has expanded beyond the initial historic treatment of neonates with respiratory failure. Patients with severe refractory cardiopulmonary failure may benefit from ECMO support until the primary insult has subsided or been treated. More recently, ECMO has been used by some centers as a bridge to transplant for irreversible organ failure. Nationwide Children's Hospital is a referral center that supports the use of ECMO as a bridge to transplant and is able to provide transport services for ECMO patients referred for transplant evaluation. In this report, we describe our design of a unique, custom-built sled designed specifically for the EC-145 helicopter to transport pediatric ECMO patients to our institution. This report is the first, to our knowledge, to describe the safe and successful transport of a pediatric ECMO patient in an EC-145 helicopter. PMID- 27255882 TI - Hot Air Balloon: An Unusual Cause of Multicasualty Trauma Incident. AB - Hot air balloon incidents are few and far between compared with the total number of flights. Nevertheless, hot air balloon incidents may produce severe trauma involving several patients and are linked to significant mortality. The prehospital management of injured patients starts after having secured potential surrounding dangers, such as fire or explosion. In the context of a rescue by helicopter, close attention must be paid to potential obstacles, like trees or electrical wires, and the risk of aspiration of the balloon envelope into the rotor. Patients involved in such incidents are often split up in a closed perimeter around the crash point. The severity of the trauma depends essentially on the height of the fall. The most frequent traumatic lesions involve fractures of the lower limbs, the spine, and the pelvis as well as severe burns caused by the balloon fire. Because of the number of patients present, an initial triage is usually required at the site. The use of rescue helicopters can be helpful. They can perform aerial reconnaissance, provide on-site high-level resources, enable access to the patients even in hostile environments, and quickly transport them to trauma center hospitals. PMID- 27255884 TI - Erratum to "Interprofessional Flight Camp" [Air Medical Journal (2016) 70-72]. PMID- 27255885 TI - Erratum to "Case Review: 17-Year-Old-Female With Respiratory Depression as a Result of Opioid Overdose" [Air Medical Journal (2016) 52]. PMID- 27255883 TI - Management of a Mass Casualty Event Caused by Electrocution Using Doctor Helicopters. AB - OBJECTIVE: This is the first report to show the use of doctor helicopters in a mass casualty event induced by electrocution. METHODS: We performed a narrative review. RESULTS: Two children obtained electrocution burns by breaking an electric fence. Five adults also received electrocution burns. Emergency medical technicians at the scene requested additional dispatch of an ambulance and the doctor helicopter. Two adult men with cardiopulmonary arrest were transported by 2 ambulances to a nearby hospital. One adult woman was in a restless confusional state, intubated, and transferred to another hospital using the doctor helicopter. One boy, who was initially in a coma, and his mother were transferred to our hospital by 1 ambulance. Another boy, who had finger amputation, was transferred to the other hospital by another doctor helicopter. A remaining elderly woman was transported to the other local hospital by ambulance. All the victims, except the 2 fathers who fell into cardiac arrest, survived. CONCLUSION: Early confirmation of the safety of the scene, early establishment of command and control, early request for dispatch of other parties and the doctor Helicopter, appropriate triage, appropriate treatment at the scene, selecting appropriate medical facilities, and dispersion transportation were crucial. PMID- 27255886 TI - Concern Network. PMID- 27255887 TI - Predictive factors for extraction site hernia after laparoscopic right colectomy. AB - PURPOSE: Incisional hernia at the extraction site (ESIH) is a common complication after laparoscopic colorectal resections. The aim of this study was to evaluate the prevalence and potential risk factors for ESIH in a large cohort study having standardized technique. METHODS: A cross-sectional study was performed including all patients who underwent elective laparoscopic right or extended right colectomy for cancer from November 2006 to October 2013 using a standard technique. All patients have been followed up for a minimum of 1 year with abdominal CT scan. RESULTS: A total of 292 patients were included with a median follow-up of 42 months. Twenty patients (6.8 %) developed ESIH. Obesity (odds ratio (OR) = 3.76, 95 % confidence interval (CI) 1.39-10.15; p = 0.009) and incision length (OR 2.86, 95 % CI 1.077-7.60; p = 0.035) significantly predisposed to the development of ESIH. CONCLUSION: This study identified that the risk of ESIH is significant after colonic resections and there are several risk factors responsible for the development of ESIH. PMID- 27255888 TI - Antibodies directed against endogenous and exogenous citrullinated antigens pre date the onset of rheumatoid arthritis. AB - BACKGROUND: Anti-citrullinated-peptide antibodies (ACPA) have been detected in individuals with developing rheumatoid arthritis (RA) before the onset of symptom, with an initially limited spectrum of reactivities that gradually broadens. The aim was to analyze the evolution of ACPA response pre-dating symptom onset, using four selected citrullinated exogenous and endogenous antigens. METHODS: A cohort of 521 individuals sampled before symptoms of RA appeared and 272 population controls were identified from the Biobank of Northern Sweden; 241 samples from patients with early RA were also collected. ACPA were detected by ELISA on viral citrullinated peptides (VCP) derived from Epstein-Barr virus nuclear antigen (EBNA)1 and EBNA2 (VCP1 and VCP2) and histone-4-derived citrullinated peptides (HCP1 and HCP2). RESULTS: In pre-symptomatic individuals vs. patients with early RA, anti-VCP1 antibodies were detected in 10.4 % vs. 36.1 %, anti-VCP2 in 17.1 % vs. 52.3 %, anti-HCP1 in 10.2 % vs. 37.3 %, and anti-HCP2 in 16.3 % vs. 48.5 %, respectively. Anti-VCP and anti-HCP concentrations were significantly increased in pre-symptomatic individuals vs. controls (p < 0.001) and were increased approaching symptom onset. Anti-VCP and anti-HCP appeared simultaneously (median (IQR) 5.3 (6) years before symptom onset) and in combination yielded a high-risk ratio for disease development (OR = 8.0-18.9). Anti-VCP2 and anti-HCP2 antibodies were associated with HLA-DRB1*0401 in pre symptomatic individuals. Three peptidylarginine deiminase (PAD)I3/PADI4 single nucleotide polymorphisms (SNPs) were significantly associated with anti-HCP1. CONCLUSIONS: Anti-VCP and anti-HCP antibodies pre-date symptom onset and predict disease development, but no hierarchy of citrullinated epitopes can be identified. These results suggest that no inciting citrullinated antigen so far described is common to all patients with RA. The association between PADI3/PADI4 polymorphism and anti-HCP1 antibodies suggests a novel link between deimination and production of ACPA. PMID- 27255889 TI - Dehydration-responsive features of Atrichum undulatum. AB - Drought is an increasingly important limitation on plant productivity worldwide. Understanding the mechanisms of drought tolerance in plants can lead to new strategies for developing drought-tolerant crops. Many moss species are able to survive desiccation-a more severe state of dehydration than drought. Research into the mechanisms and evolution of desiccation tolerance in basal land plants is of particular significance to both biology and agriculture. In this study, we conducted morphological, cytological, and physiological analyses of gametophytes of the highly desiccation-tolerant bryophyte Atrichum undulatum (Hedw.) P. Beauv during dehydration and rehydration. Our results suggested that the mechanisms underlying the dehydration-recovery cycle in A. undulatum gametophytes include maintenance of membrane stability, cellular structure protection, prevention of reactive oxygen species (ROS) generation, elimination of ROS, protection against ROS-induced damage, and repair of ROS-induced damage. Our data also indicate that this dehydration-recovery cycle consists not only of the physical removal and addition of water, but also involves a highly organized series of cytological, physiological, and biochemical changes. These attributes are similar to those reported for other drought- and desiccation-tolerant plant species. Our findings provide major insights into the mechanisms of dehydration-tolerance in the moss A. undulatum. PMID- 27255890 TI - Impact of Social Networking Sites on Children in Military Families. AB - Youth in military families experience a relatively unique set of stressors that can put them at risk for numerous psychological and behavior problems. Thus, there is a need to identify potential mechanisms by which children can gain resiliency against these stressors. One potential mechanism that has yet to be empirically studied with military youth is social networking sites (SNSs). SNSs have gained significant popularity among society, especially youth. Given the significance of these communication tools in youths' lives, it is important to analyze how SNS use may affect military youth and their ability to cope with common military life stressors. The current review examines the potential positive and negative consequences associated with SNS use in coping with three common stressors of youth in military families: parent deployment, frequent relocation, and having a family member with a psychological or physical disability. By drawing from SNS and military literature, we predict that SNS use can be a positive tool for helping children in military families to cope with stressors. However, certain SNS behaviors can potentially result in more negative outcomes. Recommendations for future research are also discussed. PMID- 27255892 TI - Salt Plug Formation Caused by Decreased River Discharge in a Multi-channel Estuary. AB - Freshwater input to estuaries may be greatly altered by the river barrages required to meet human needs for drinking water and irrigation and prevent salt water intrusion. Prior studies have examined the salt plugs associated with evaporation and salt outwelling from tidal salt flats in single-channel estuaries. In this work, we discovered a new type of salt plug formation in the multi-channel Pasur River Estuary (PRE) caused by decreasing river discharges resulting from an upstream barrage. The formation of a salt plug in response to changes in river discharge was investigated using a conductivity-temperature depth (CTD) recorder during spring and neap tides in the dry and wet seasons in 2014. An exportation of saline water from the Shibsa River Estuary (SRE) to the PRE through the Chunkhuri Channel occurred during the dry season, and a salt plug was created and persisted from December to June near Chalna in the PRE. A discharge-induced, relatively high water level in the PRE during the wet season exerted hydrostatic pressure towards the SRE from the PRE and thereby prevented the intrusion of salt water from the SRE to the PRE. PMID- 27255891 TI - Worry is associated with robust reductions in heart rate variability: a transdiagnostic study of anxiety psychopathology. AB - BACKGROUND: Individuals with anxiety disorders display reduced resting-state heart rate variability (HRV), although findings have been contradictory and the role of specific symptoms has been less clear. It is possible that HRV reductions may transcend diagnostic categories, consistent with dimensional-trait models of psychopathology. Here we investigated whether anxiety disorders or symptoms of anxiety, stress, worry and depression are more strongly associated with resting state HRV. METHODS: Resting-state HRV was calculated in participants with clinical anxiety (n = 25) and healthy controls (n = 58). Symptom severity measures of worry, anxiety, stress, and depression were also collected from participants, regardless of diagnosis. RESULTS: Participants who fulfilled DSM-IV criteria for an anxiety disorder displayed diminished HRV, a difference at trend level significance (p = .1, Hedges' g = -.37, BF10 = .84). High worriers (Total n = 41; n = 22 diagnosed with an anxiety disorder and n = 19 not meeting criteria for any psychopathology) displayed a robust reduction in resting state HRV relative to low worriers (p = .001, Hedges' g = -.75, BF10 = 28.16). CONCLUSIONS: The specific symptom of worry - not the diagnosis of an anxiety disorder - was associated with the most robust reductions in HRV, indicating that HRV may provide a transdiagnostic biomarker of worry. These results enhance understanding of the relationship between the cardiac autonomic nervous system and anxiety psychopathology, providing support for dimensional-trait models consistent with the Research Domain Criteria framework. PMID- 27255893 TI - Meta-analysis suggests that the electromagnetic technique is better than the free hand method for the distal locking during intramedullary nailing procedures. AB - OBJECTIVES: To evaluate the comparative effectiveness and accuracy of electromagnetic technique (EM) verses free-hand method (FH) for distal locking in intramedullary nailing procedure. MATERIAL AND METHODS: Relevant original studies were searched in Medline, Pubmed, Embase, China National Knowledge Infrastructure, and Cochrane Central Database (all through October 2015). Comparative studies providing sufficient data of interest were included in this meta-analysis. The Stata 11.0 was used to analyze all data. RESULTS: Eight studies involving 611 participants were included, with 305 in EM group and 306 in FH group. EM outperformed FH with reduced distal locking time of 4.1 minutes [standardized mean difference (SMD), 1.61; 95 % confidence interval (95 %CI), 0.81 to 2.41] and the reduced fluoroscopy time of 25.3 seconds (SMD, 2.64; 95 %CI, 2.12 to 3.16). Regarding the accuracy of distal screw placement, no significant difference was observed between two techniques (OR, 2.39; 95 %CI, 0.38 to 15.0). There was a trend of longer operative time in FH versus EM by 10 minutes (79.0 and 69.0 minutes), although the difference was not statistically significant (SMD, 0.341; 95 % CI, -0.02 to 0.703). CONCLUSIONS: The existing evidence suggests EM technique is a better alternative for distal locking in intramedullary nailing procedure, and this might aid in the management of diaphyseal fractures in lower extremities. PMID- 27255894 TI - Spermine cycling in mitochondria is mediated by adenine nucleotide translocase activity: mechanism and pathophysiological implications. AB - Spermine, besides to be transported in mitochondria by an energy dependent electrophoretic mechanism, can be also released by two different mechanisms. The first one is induced in deenergizing conditions by FCCP or antimycin A and it is mediated by an electroneutral exchange spermine protons. The second one takes place in energizing conditions during the activity of the adenine nucleotide translocase and is mediated by an electroneutral symport mechanism involving the efflux in co-transport of spermine and phosphate and the exchange of exogenous ADP with endogenous ATP. The triggering of this mechanism permits an alternating cycling of spermine across the mitochondrial membrane, that is spermine is transported or released by energized mitochondria in the absence or presence of ATP synthesis, respectively. The physiological implications of this cycling of spermine are related to the induction or prevention of mitochondrial permeability transition and, consequently, on apoptosis or its prevention. PMID- 27255895 TI - The AR/NCOA1 axis regulates prostate cancer migration by involvement of PRKD1. AB - Due to the urgent need for new prostate cancer (PCa) therapies, the role of androgen receptor (AR)-interacting proteins should be investigated. In this study we aimed to address whether the AR coactivator nuclear receptor coactivator 1 (NCOA1) is involved in PCa progression. Therefore, we tested the effect of long term NCOA1 knockdown on processes relevant to metastasis formation. [(3)H] thymidine incorporation assays revealed a reduced proliferation rate in AR positive MDA PCa 2b and LNCaP cells upon knockdown of NCOA1, whereas AR-negative PC3 cells were not affected. Furthermore, Boyden chamber assays showed a strong decrease in migration and invasion upon NCOA1 knockdown, independently of the cell line's AR status. In order to understand the mechanistic reasons for these changes, transcriptome analysis using cDNA microarrays was performed. Protein kinase D1 (PRKD1) was found to be prominently up-regulated by NCOA1 knockdown in MDA PCa 2b, but not in PC3 cells. Inhibition of PRKD1 reverted the reduced migratory potential caused by NCOA1 knockdown. Furthermore, PRKD1 was negatively regulated by AR. Immunohistochemical staining of PCa patient samples revealed a strong increase in NCOA1 expression in primary tumors compared with normal prostate tissue, while no final conclusion could be drawn for PRKD1 expression in tumor specimens. Thus, our findings directly associate the AR/NCOA1 complex with PRKD1 regulation and cellular migration and support the concept of therapeutic inhibition of NCOA1 in PCa. PMID- 27255896 TI - D-Peptides as Recognition Molecules and Therapeutic Agents. AB - Over recent years, D-peptides have attracted increasing attention. D-peptides increase enzymatic stability, prolong the plasma half-life, improve oral bioavailability, and enhance binding activity and specificity with receptor or target proteins, in comparison with the corresponding L-peptide. Therefore, D peptides are considered to have potential as recognition molecules and therapeutic agents. This review focuses on the design and application of D peptides with biological activity. PMID- 27255897 TI - Polarization memory effect in the photoluminescence of nc-Si-SiOx light-emitting structures. AB - The polarization memory (PM) effect in the photoluminescence (PL) of the porous nc-Si-SiOx light-emitting structures, containing nanoparticles of silicon (nc-Si) in the oxide matrix and passivated in a solution of hydrofluoric acid (HF), has been investigated. The studied nc-Si-SiOx structures were produced by evaporation of Si monoxide (SiO) powder in vacuum and oblique deposition on Si wafer, and then the deposited silicon oxide (SiOx) films were annealed in the vacuum at 975 degrees C to grow nc-Si. It was found that the PM effect in the PL is observed only after passivation of nanostructures: during etching in HF solution, the initial symmetric nc-Si becomes asymmetric elongated. It was also found that in investigated nanostructures, there is a defined orientational dependence of the PL polarization degree (rho) in the sample plane which correlates with the orientation of SiOx nanocolumns, forming the structure of the porous layer. The increase of the rho values in the long-wavelength spectral range with time of HF treatment can be associated with increasing of the anisotropy of large Si nanoparticles. The PM effect for this spectral interval can be described by the dielectric model. In the short-wavelength spectral range, the dependence of the rho values agrees qualitatively with the quantum confinement effect. PMID- 27255898 TI - CO and Soot Oxidation over Ce-Zr-Pr Oxide Catalysts. AB - A set of ceria, ceria-zirconia (Ce 80 at.%, Zr 20 at.%), ceria-praseodymia (Ce 80 at.%, Pr 20 at.%) and ceria-zirconia-praseodymia (Ce 80 at.%, Zr 10 at.% and Pr 10 at.%) catalysts has been prepared by the solution combustion synthesis (SCS). The effects of Zr and Pr as dopants on ceria have been studied in CO and soot oxidation reactions. All the prepared catalysts have been characterized by complementary techniques, including XRD, FESEM, N2 physisorption at -196 degrees C, H2-temperature-programmed reduction, and X-ray photoelectron spectroscopy to investigate the relationships between the structure and composition of materials and their catalytic performance. Better results for CO oxidation have been obtained with mixed oxides (performance scale, Ce80Zr10Pr10 > Ce80Zr20 > Ce80Pr20) rather than pure ceria, thus confirming the beneficial role of multicomponent catalysts for this prototypical reaction. Since CO oxidation occurs via a Mars-van Krevelen (MvK)-type mechanism over ceria-based catalysts, it appears that the presence of both Zr and Pr species into the ceria framework improves the oxidation activity, via collective properties, such as electrical conductivity and surface or bulk oxygen anion mobility. On the other hand, this positive effect becomes less prominent in soot oxidation, since the effect of catalyst morphology prevails. PMID- 27255899 TI - Synergistic Effects of Gold Nanocages in Hyperthermia and Radiotherapy Treatment. AB - Gold nanocages (GNCs) are a promising material that not only converts near infrared (NIR) light to heat for the ablation of tumors but also acts as a radiosensitizer. The combination of hyperthermia and radiotherapy has a synergistic effect that can lead to significant tumor cell necrosis. In the current study, we synthesized GNCs that offered the combined effects of hyperthermia and radiotherapy. This combination strategy resulted in increased tumor cell apoptosis and significant tumor tissue necrosis. We propose that GNCs can be used for clinical treatment and to potentially overcome resistance to radiotherapy by clearly increasing the antitumor effect. PMID- 27255900 TI - Influence of GaAsBi Matrix on Optical and Structural Properties of InAs Quantum Dots. AB - InAs/GaAsBi dot-in-well structures were fabricated using gas-source molecular beam epitaxy and investigated for its optical and structural properties. GaAsBi strained buffer layer and strain reduction layer are both effective to extend the photoluminescence (PL) emission wavelength of InAs quantum dot (QD). In addition, a remarkable PL intensity enhancement is also obtained compared with low temperature-grown GaAs-capped InAs QD sample. The GaAsBi matrix also preserves the shape of InAs QDs and leads to increase the activation energy for nonradiative recombination process at low temperature. Lower density and larger size of InAs QDs are obtained on the GaAsBi surface compared with the QDs grown on GaAs surface. PMID- 27255901 TI - Piezo-phototronic effect enhanced UV photodetector based on CuI/ZnO double-shell grown on flexible copper microwire. AB - In this work, we present a facile, low-cost, and effective approach to fabricate the UV photodetector with a CuI/ZnO double-shell nanostructure which was grown on common copper microwire. The enhanced performances of Cu/CuI/ZnO core/double shell microwire photodetector resulted from the formation of heterojunction. Benefiting from the piezo-phototronic effect, the presentation of piezocharges can lower the barrier height and facilitate the charge transport across heterojunction. The photosensing abilities of the Cu/CuI/ZnO core/double-shell microwire detector are investigated under different UV light densities and strain conditions. We demonstrate the I-V characteristic of the as-prepared core/double shell device; it is quite sensitive to applied strain, which indicates that the piezo-phototronic effect plays an essential role in facilitating charge carrier transport across the CuI/ZnO heterojunction, then the performance of the device is further boosted under external strain. PMID- 27255902 TI - Droplet etching of deep nanoholes for filling with self-aligned complex quantum structures. AB - Strain-free epitaxial quantum dots (QDs) are fabricated by a combination of Al local droplet etching (LDE) of nanoholes in AlGaAs surfaces and subsequent hole filling with GaAs. The whole process is performed in a conventional molecular beam epitaxy (MBE) chamber. Autocorrelation measurements establish single-photon emission from LDE QDs with a very small correlation function g ((2))(0)? 0.01 of the exciton emission. Here, we focus on the influence of the initial hole depth on the QD optical properties with the goal to create deep holes suited for filling with more complex nanostructures like quantum dot molecules (QDM). The depth of droplet etched nanoholes is controlled by the droplet material coverage and the process temperature, where a higher coverage or temperature yields deeper holes. The requirements of high quantum dot uniformity and narrow luminescence linewidth, which are often found in applications, set limits to the process temperature. At high temperatures, the hole depths become inhomogeneous and the linewidth rapidly increases beyond 640 degrees C. With the present process technique, we identify an upper limit of 40-nm hole depth if the linewidth has to remain below 100 MUeV. Furthermore, we study the exciton fine-structure splitting which is increased from 4.6 MUeV in 15-nm-deep to 7.9 MUeV in 35-nm-deep holes. As an example for the functionalization of deep nanoholes, self-aligned vertically stacked GaAs QD pairs are fabricated by filling of holes with 35 nm depth. Exciton peaks from stacked dots show linewidths below 100 MUeV which is close to that from single QDs. PMID- 27255903 TI - Non-adiabatic molecular dynamic simulations of opening reaction of molecular junctions. AB - We report non-adiabatic molecular dynamic simulations of the ring opening reaction of diarylethene (DAE) derivative molecules, both free standing and embedded between gold electrodes. Simulations are performed by the surface hopping method employing density functional theory. Typically, the free-standing molecules exhibit large quantum yields to open and close; however the process is quenched for the molecules embedded between electrodes. Our simulations reveal the importance of the DAE side chemical groups, which explain the efficiency of the quenching process. Namely, delocalization of the LUMO state contributes to electronic coupling between the molecule and electrodes, suppressing or enhancing the reaction process. The simulations indicate that a proper choice of the chemical side group, which provides the strong localization of the LUMO state, can substantially diminish the quenching mechanism. Additionally, we analyze a strong dependency of the quantum yield of the opening reaction coming from the mechanical strength of the molecules. PMID- 27255904 TI - Defining small-for-gestational-age: prescriptive versus descriptive birthweight standards. AB - Descriptive population-based birthweight standards possess low sensitivity in detecting infants with growth impairment. A prescriptive birthweight standard based on a 'healthy' subpopulation without risk factors for intrauterine growth restriction might be superior. We created two birthweight standards based on live born, singleton infants with gestational age 24-42 weeks and born in The Netherlands between 2000 and 2007. Inclusion criteria for the prescriptive birthweight standard were restricted to infants without congenital malformations, born to healthy mothers after uncomplicated pregnancies. We defined small-for gestational-age (SGA) as birthweight <10th percentile and assessed the ability of both standards to predict adverse neonatal outcomes. The prescriptive birthweight standard identified significantly more infants as SGA, up to 38.0 % at 29 weeks gestation. SGA infants classified according to both standards as well as those classified according to the prescriptive birthweight standard only, were at increased risk of both major and minor adverse neonatal outcomes. The prescriptive birthweight standard was both more sensitive and less specific, with a maximum increase in sensitivity predicting bronchopulmonary dysplasia (+42.6 %) and a maximum decrease in specificity predicting intraventricular haemorrhage ( 26.9 %) in infants aged 28-31 weeks. CONCLUSION: Prescriptive birthweight standards could improve identification of infants born SGA and at risk of adverse neonatal outcomes. WHAT IS KNOWN: * Descriptive birthweight standards possess low sensitivity in detecting growth restricted infants at risk of adverse neonatal outcomes. * Prescriptive standards could improve identification of very preterm small-for-gestational-age (SGA) infants at risk of intraventricular haemorrhage. What is New: * Prescriptive standards identify more preterm and term SGA infants at risk of major adverse neonatal outcomes. * Late preterm and term SGA infants classified according to the prescriptive standard are at increased risk of minor adverse neonatal outcomes with potentially harmful implications. PMID- 27255905 TI - [Manual medicine and osteopathic methods on the growing spine]. AB - The application of various techniques in manual medicine on infants, toddlers and adolescents enjoys widespread acknowledgement not only in the musculoskeletal field but also beyond that. For a long time, the seminars of the DGMM have been trying to structure the advanced training of doctors and the vocational training of physiotherapists and to adjust it according to the latest clinical and scientific findings (in this subject matter). Considering the controversial debates, this seems particularly necessary and meaningful. This article aims to identify the current state of discussion and the consensus between medical associations but it also means to provide assistance in daily routine. PMID- 27255907 TI - India increases retirement age of government doctors to 65. PMID- 27255906 TI - [Injuries of the thoracolumbar spine in children]. AB - BACKGROUND: Injuries of the thoracolumbar spine in children are rare and challenging for the treating physician. Besides knowledge of fracture treatment, the anatomical particularities of the spine in children are of great importance. METHODS: The article gives an overview of the diagnosis and therapy with the most common classification of injuries of the thoracolumbar spine. RESULTS: Taking into account the children's age and the fracture morphology most cases can be treated conservatively, especially because the young spine has great potential for remodelling. The older the child becomes, the more smoothly the transition to adult treatment occurs; thus, unstable fractures should be treated with surgery. CONCLUSION: The difficult indication and the specific characteristics of surgery necessitate treatment in a spine centre with experience with surgery on children. PMID- 27255908 TI - Evaluation of the effectiveness of robotic gait training and gait-focused physical therapy programs for children and youth with cerebral palsy: a mixed methods RCT. AB - BACKGROUND: Robot assisted gait training (RAGT) is considered to be a promising approach for improving gait-related gross motor function of children and youth with cerebral palsy. However, RAGT has yet to be empirically demonstrated to be effective. This knowledge gap is particularly salient given the strong interest in this intensive therapy, the high cost of the technology, and the requirement for specialized rehabilitation centre resources. METHODS: This is a research protocol describing a prospective, multi-centre, concurrent mixed methods study comprised of a randomized controlled trial (RCT) and an interpretive descriptive qualitative design. It is a mixed methods study designed to determine the relative effectiveness of three physical therapy treatment conditions (i.e., RAGT, a functional physical therapy program conducted over-ground (fPT), and RAGT + fPT) on gait related motor skills of ambulatory children with cerebral palsy. Children with cerebral palsy aged 5-18 years who are ambulatory (Gross Motor Function Classification System Levels II and III) will be randomly allocated to one of four treatment conditions: 1) RAGT, 2) fPT, 3) RAGT and fPT combined, or 4) a maintenance therapy only control group. The qualitative component will explicate child and parent experiences with the interventions, provide insight into the values that underlie their therapy goals, and assist with interpretation of the results of the RCT. DISCUSSION: n/a. TRIAL REGISTRATION: NCT02391324 Registered March 12, 2015. PMID- 27255909 TI - Acquired partial lipodystrophy (Barraquer-Simons syndrome) and IgA nephropathy. PMID- 27255910 TI - Thirteen treated of acute renal failure secondary to multiple myeloma with high cut off filters. AB - INTRODUCTION: Multiple myeloma (MM) is a haematological tumour that is characterised by uncontrolled proliferation of plasma cells and a significant volume of serum free light chains (sFLCs), which can cause acute renal failure due to intratubular precipitation, resulting in cast nephropathy. Acute renal failure is a complication that can arise in more than 20% of patients with multiple myeloma, half of which will require dialysis. METHODS: We report our experience with 13 patients who were treated with dialysis using high cut off filters (HCO) between July 2011 and February 2015. A total of 6 consecutive 6 hour sessions were performed using a 2.1 m(2) HCO filter (Theralite(r) by Gambro(r)). Afterwards, further 6-hour sessions were continued on alternate days. RESULTS: A total of 151 sessions were conducted, with an average of 11.6 sessions per patient (range 6-27). The treatment proved to be effective in removing both kappa and lambda sFLCs, resulting in a 93.7% fall in sFLCs by the end of treatment. The average reduction was 57.7% per dialysis session. 10 out of the 13 cases recovered sufficient renal function to become independent of dialysis. There were no major changes in albumin levels using an infusion protocol of 2 50 mL vials of 20% albumin at the end of the dialysis session. CONCLUSIONS: Combination treatment with chemotherapy and long dialysis with HCO filters was effective in reducing the sFLC levels and recovering sufficient renal function in 77% of cases. With HCO filters, significant cost savings are achieved, contrary to what was previously believed. PMID- 27255911 TI - Phenotypic and genetic characteristics of Vibrio cholerae O1 carrying Haitian ctxB and attributes of classical and El Tor biotypes isolated from Silvassa, India. AB - Vibrio cholerae O1 biotype El Tor, the causative agent of the seventh pandemic, has recently been replaced by strains carrying classical and Haitian ctxB in India, Haiti and other parts of the world. We conducted phenotypic and genetic tests to characterize V. cholerae O1 isolated between 2012 and 2014 from Silvassa, India, to examine the presence of virulence and regulatory genes, seventh pandemic marker, ctxB type and biofilm formation and to study genomic diversity. Of the 59 V. cholerae O1, eight isolates belong to El Tor prototype, one to classical prototype and the remaining isolates have attributes of both classical and El Tor biotypes. PCR and ctxB gene sequencing revealed the presence of classical ctxB in four strains and Haitian ctxB in 55 isolates; indicating that isolates were either an El Tor or hybrid variant. All isolates carried virulence, regulatory, adherence, Vibrio seventh pandemic pathogenicity island I and seventh pandemic group-specific marker VC2346, in addition to tcpAET and rstRET, the features of seventh pandemic strains, and produced cholera toxin and biofilm. PFGE analysis showed that the majority of isolates are clonal and belong to fingerprint pattern A; however, pattern B is unrelated and patterns C and D are distinct, suggesting considerable diversity in the genomic content among them. These data thus show that isolates from Silvassa are genetically diverse and that Haitian ctxB and hybrid phenotypes are undergoing global dissemination. PMID- 27255912 TI - Expectations of relatives of Syrian patients in intensive care units in a state hospital in Turkey. AB - AIMS AND OBJECTIVES: The purpose of the study was to describe the personal experiences of relatives of Syrian patients in the intensive care unit in one hospital in Turkey. BACKGROUND: The concept of the intensive care unit can be particularly frightening for family members. Current recommendations for training Intensive care unit nurses should support a holistic approach to patient (and family) care, including explanations at a level that families can easily understand and allowing family members to see the patient at regular intervals. DESIGN: This qualitative study was conducted between June and August 2014 and included a study sample of 30 Syrian family members related to patients receiving treatment at a state hospital intensive care unit in Turkey. METHODS: Data were collected by semi-structured interviews. We used percentages to represent descriptive data and conducted qualitative content analysis. RESULTS: Following data analysis, six themes arose: (1) communication-related difficulties, (2) difficulties receiving information regarding the patient's condition, (3) difficulties meeting personal needs, (4) difficulties communicating with other family members, (5) difficulties receiving support from other family members, and (6) unmet expectations from nurses and hospital administration. CONCLUSIONS: Syrian patient's relatives receiving treatment in an intensive care unit in Turkey experienced communication difficulties in terms of receiving information from health care personnel, informing other family members, receiving social support from other family members, and having various unmet expectations from nurses and hospital administration. RELEVANCE TO CLINICAL PRACTICE: The results of this study can be used to develop guidelines and predictions for scenarios that are likely to arise for patients' relatives from foreign countries who arrive to support patients who receive healthcare services in our increasingly global world. PMID- 27255915 TI - Predicting disease trait with genomic data: a composite kernel approach. AB - With the advancement of biotechniques, a vast amount of genomic data is generated with no limit. Predicting a disease trait based on these data offers a cost effective and time-efficient way for early disease screening. Here we proposed a composite kernel partial least squares (CKPLS) regression model for quantitative disease trait prediction focusing on genomic data. It can efficiently capture nonlinear relationships among features compared with linear learning algorithms such as Least Absolute Shrinkage and Selection Operator or ridge regression. We proposed to optimize the kernel parameters and kernel weights with the genetic algorithm (GA). In addition to improved performance for parameter optimization, the proposed GA-CKPLS approach also has better learning capacity and generalization ability compared with single kernel-based KPLS method as well as other nonlinear prediction models such as the support vector regression. Extensive simulation studies demonstrated that GA-CKPLS had better prediction performance than its counterparts under different scenarios. The utility of the method was further demonstrated through two case studies. Our method provides an efficient quantitative platform for disease trait prediction based on increasing volume of omics data. PMID- 27255914 TI - Embracing an integromic approach to tissue biomarker research in cancer: Perspectives and lessons learned. AB - Modern approaches to biomedical research and diagnostics targeted towards precision medicine are generating 'big data' across a range of high-throughput experimental and analytical platforms. Integrative analysis of this rich clinical, pathological, molecular and imaging data represents one of the greatest bottlenecks in biomarker discovery research in cancer and other diseases. Following on from the publication of our successful framework for multimodal data amalgamation and integrative analysis, Pathology Integromics in Cancer (PICan), this article will explore the essential elements of assembling an integromics framework from a more detailed perspective. PICan, built around a relational database storing curated multimodal data, is the research tool sitting at the heart of our interdisciplinary efforts to streamline biomarker discovery and validation. While recognizing that every institution has a unique set of priorities and challenges, we will use our experiences with PICan as a case study and starting point, rationalizing the design choices we made within the context of our local infrastructure and specific needs, but also highlighting alternative approaches that may better suit other programmes of research and discovery. Along the way, we stress that integromics is not just a set of tools, but rather a cohesive paradigm for how modern bioinformatics can be enhanced. Successful implementation of an integromics framework is a collaborative team effort that is built with an eye to the future and greatly accelerates the processes of biomarker discovery, validation and translation into clinical practice. PMID- 27255913 TI - Severe hypoxemia: which strategy to choose. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is characterized by a noncardiogenic pulmonary edema with bilateral chest X-ray opacities and reduction in lung compliance, and the hallmark of the syndrome is hypoxemia refractory to oxygen therapy. Severe hypoxemia (PaO2/FiO2 < 100 mmHg), which defines severe ARDS, can be found in 20-30 % of the patients and is associated with the highest mortality rate. Although the standard supportive treatment remains mechanical ventilation (noninvasive and invasive), possible adjuvant therapies can be considered. We performed an up-to-date clinical review of the possible available strategies for ARDS patients with severe hypoxemia. MAIN RESULTS: In summary, in moderate-to-severe ARDS or in the presence of other organ failure, noninvasive ventilatory support presents a high risk of failure: in those cases the risk/benefit of delayed mechanical ventilation should be evaluated carefully. Tailoring mechanical ventilation to the individual patient is fundamental to reduce the risk of ventilation-induced lung injury (VILI): it is mandatory to apply a low tidal volume, while the optimal level of positive end-expiratory pressure should be selected after a stratification of the severity of the disease, also taking into account lung recruitability; monitoring transpulmonary pressure or airway driving pressure can help to avoid lung overstress. Targeting oxygenation of 88-92 % and tolerating a moderate level of hypercapnia are a safe choice. Neuromuscular blocking agents (NMBAs) are useful to maintain patient ventilation synchrony in the first hours; prone positioning improves oxygenation in most cases and promotes a more homogeneous distribution of ventilation, reducing the risk of VILI; both treatments, also in combination, are associated with an improvement in outcome if applied in the acute phase in the most severe cases. The use of extracorporeal membrane oxygenation (ECMO) in severe ARDS is increasing worldwide, but because of a lack of randomized trials is still considered a rescue therapy. CONCLUSION: Severe ARDS patients should receive a holistic framework of respiratory and hemodynamic support aimed to ensure adequate gas exchange while minimizing the risk of VILI, by promoting lung recruitment and setting protective mechanical ventilation. In the most severe cases, NMBAs, prone positioning, and ECMO should be considered. PMID- 27255916 TI - Circular RNA: an emerging key player in RNA world. AB - Insights into the circular RNA (circRNA) exploration have revealed that they are abundant in eukaryotic transcriptomes. Diverse genomic regions can generate different types of RNA circles, implying their diversity. Covalently closed loop structures elevate the stability of this new type of noncoding RNA. High throughput sequencing analyses suggest that circRNAs exhibit tissue- and developmental-specific expression, indicating that they may play crucial roles in multiple cellular processes. Strikingly, several circRNAs could function as microRNA sponges and regulate gene transcription, highlighting a new class of important regulators. Here, we review the recent advances in knowledge of endogenous circRNA biogenesis, properties and functions. We further discuss the current findings about circRNAs in human diseases. In plants, the roles of circRNAs remain a mystery. Online resources and bioinformatics identification of circRNAs are essential for the analysis of circRNA biology, although different strategies yield divergent results. The understanding of circRNA functions remains limited; however, circRNAs are enriching the RNA world, acting as an emerging key player. PMID- 27255917 TI - Addenbrooke's cognitive examination test for brief cognitive assessment of adolescents suffering from migraine with aura. AB - The aim of this study was to assess the role of the Addenbrooke's cognitive examination test (ACE-R) in the evaluation of cognitive status in migraineurs interictally. A total of 44 adolescent patients and 44 healthy controls, matched by age and gender, have undergone ACE-R testing. Migraineurs were additionally questioned about migraine aura features and presence of higher cortical dysfunctions (HCD) during an aura. According to the questionnaire results, patients were subsequently divided into HCD and Non-HCD group. ACE-R scores of migraine patients were significantly lower than in healthy controls (93.68 +/- 3.64 vs 96.91 +/- 2.49; t = 4.852, p < 0.001). Also, subscores of memory and verbal fluency were significantly higher in the control population. There was no correlation of HCD occurrence with cognitive examination score, although Non-HCD subgroup achieved better score (93.13 +/- 3.91 vs 94.29 +/- 3.30; t = 1.053, p = 0.298). Findings have shown that migraineurs get lower ACE-R test scores, with a tendency to have a poorer outcome in more complex aura. Also, our study has revealed that the ACE-R test is an easily administered test for brief assessment of cognitive status in migraineurs. Future perspectives could be further evaluation of ACE-R test in larger sample size and the impact of migraine with aura on cognitive function in adolescents. PMID- 27255918 TI - Isolated hypoglossal nerve paralysis and hypoglossal-vertebral entrapment syndrome. PMID- 27255919 TI - Effects of deoxynivalenol (DON), zearalenone (ZEN), and related metabolites on equine peripheral blood mononuclear cells (PBMC) in vitro and background occurrence of these toxins in horses. AB - Both deoxynivalenol (DON), zearalenone (ZEN), and their metabolites are known to modulate immune cells in various species whereby viability and proliferation are influenced. Such effects were rarely examined in horses. Therefore, one aim of the present study was to titrate the inhibitory concentrations of DON, 3-acetyl DON (3AcDON), de-epoxy-DON (DOM-1), ZEN, and alpha- and beta-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC50) and 10 % (IC10) in vitro. For evaluation of practical relevance of the in vitro findings, a further aim was to screen horses for the background occurrence of DON, ZEN, and their metabolites in systemic circulation and to relate toxin residues both to the inhibitory toxin concentrations and to hematological and clinical-chemical characteristics.The IC50 (MUM) for DON, 3AcDON, beta-ZEL, alpha ZEL, and ZEN were determined at 3.09, 25.90, 75.44, 97.44, and 98.15 in unstimulated cells, respectively, while in proliferating cells, the corresponding IC50 values were 0.73, 6.89, 45.16, 75.96, and 82.51. Neither viability nor proliferation was influenced by DOM-1 up to a concentration of 100 MUM.The in vivo screening (N = 49) revealed the occurrence of ZEN (N = 24), alpha-ZEL (N = 3), beta-ZEL (N = 37), DON, and DOM-1 (N = 2). The detected concentrations were much lower than the corresponding IC50 while the IC10 of DON and beta-ZEL for proliferating PBMC corresponded to approximately 26 and 35 ng/mL which might be relevant when contaminated diets are fed.Clinical-chemical and hematological traits were not related to mycotoxin residue levels excepting blood urea nitrogen which was positively correlated to the sum of beta-ZEL, alpha-ZEL, and ZEN concentration. Whether this reflects simply the feeding history of the horses or renal failures giving rise to a prolonged half-life of the toxins needs to be clarified further. PMID- 27255920 TI - Evaluation of the free, open source software WordPress as electronic portfolio system in undergraduate medical education. AB - BACKGROUND: Electronic portfolios (ePortfolios) are used to document and support learning activities. E-portfolios with mobile capabilities allow even more flexibility. However, the development or acquisition of ePortfolio software is often costly, and at the same time, commercially available systems may not sufficiently fit the institution's needs. The aim of this study was to design and evaluate an ePortfolio system with mobile capabilities using a commercially free and open source software solution. METHODS: We created an online ePortfolio environment using the blogging software WordPress based on reported capability features of such software by a qualitative weight and sum method. Technical implementation and usability were evaluated by 25 medical students during their clinical training by quantitative and qualitative means using online questionnaires and focus groups. RESULTS: The WordPress ePortfolio environment allowed students a broad spectrum of activities - often documented via mobile devices - like collection of multimedia evidences, posting reflections, messaging, web publishing, ePortfolio searches, collaborative learning, knowledge management in a content management system including a wiki and RSS feeds, and the use of aid tools for studying. The students' experience with WordPress revealed a few technical problems, and this report provides workarounds. The WordPress ePortfolio was rated positively by the students as a content management system (67 % of the students), for exchange with other students (74 %), as a note pad for reflections (53 %) and for its potential as an information source for assessment (48 %) and exchange with a mentor (68 %). On the negative side, 74 % of the students in this pilot study did not find it easy to get started with the system, and 63 % rated the ePortfolio as not being user-friendly. Qualitative analysis indicated a need for more introductory information and training. CONCLUSIONS: It is possible to build an advanced ePortfolio system with mobile capabilities with the free and open source software WordPress. This allows institutions without proprietary software to build a sophisticated ePortfolio system adapted to their needs with relatively few resources. The implementation of WordPress should be accompanied by introductory courses in the use of the software and its apps in order to facilitate its usability. PMID- 27255921 TI - On the domain-specificity of the visual and non-visual face-selective regions. AB - What happens in our brains when we see a face? The neural mechanisms of face processing - namely, the face-selective regions - have been extensively explored. Research has traditionally focused on visual cortex face-regions; more recently, the role of face-regions outside the visual cortex (i.e., non-visual-cortex face regions) has been acknowledged as well. The major quest today is to reveal the functional role of each this region in face processing. To make progress in this direction, it is essential to understand the extent to which the face-regions, and particularly the non-visual-cortex face-regions, process only faces (i.e., face-specific, domain-specific processing) or rather are involved in a more domain-general cognitive processing. In the current functional MRI study, we systematically examined the activity of the whole face-network during face unrelated reading task (i.e., written meaningful sentences with content unrelated to faces/people and non-words). We found that the non-visual-cortex (i.e., right lateral prefrontal cortex and posterior superior temporal sulcus), but not the visual cortex face-regions, responded significantly stronger to sentences than to non-words. In general, some degree of sentence selectivity was found in all non visual-cortex cortex. Present result highlights the possibility that the processing in the non-visual-cortex face-selective regions might not be exclusively face-specific, but rather more or even fully domain-general. In this paper, we illustrate how the knowledge about domain-general processing in face regions can help to advance our general understanding of face processing mechanisms. Our results therefore suggest that the problem of face processing should be approached in the broader scope of cognition in general. PMID- 27255922 TI - Eating disorders among fashion models: a systematic review of the literature. AB - PURPOSE: In the light of recent concerns regarding the eating disorders among fashion models and professional regulations of fashion model occupation, an examination of the scientific evidence on this issue is necessary. The article reviews findings on the prevalence of eating disorders and body image concerns among professional fashion models. METHOD: A systematic literature search was conducted using ProQUEST, EBSCO, PsycINFO, SCOPUS, and Gale Canage electronic databases. RESULTS: A very low number of studies conducted on fashion models and eating disorders resulted between 1980 and 2015, with seven articles included in this review. Overall, results of these studies do not indicate a higher prevalence of eating disorders among fashion models compared to non-models. Fashion models have a positive body image and generally do not report more dysfunctional eating behaviors than controls. However, fashion models are on average slightly underweight with significantly lower BMI than controls, and give higher importance to appearance and thin body shape, and thus have a higher prevalence of partial-syndrome eating disorders than controls. CONCLUSION: Despite public concerns, research on eating disorders among professional fashion models is extremely scarce and results cannot be generalized to all models. The existing research fails to clarify the matter of eating disorders among fashion models and given the small number of studies, further research is needed. PMID- 27255923 TI - A cluster-randomized, controlled trial of nutritional supplementation and promotion of responsive parenting in Madagascar: the MAHAY study design and rationale. AB - BACKGROUND: Over half of the world's children suffer from poor nutrition, and as a consequence they experience delays in physical and mental health, and cognitive development. There is little data evaluating the effects of delivery of lipid based, nutrition supplementation on growth and development during pregnancy and early childhood within the context of a scaled-up program. Furthermore, there is limited evidence on effects of scaled-up, home-visiting programs that focus on the promotion of child development within the context of an existing, national nutrition program. METHODS/DESIGN: The MAHAY ("smart" in Malagasy) study uses a multi-arm randomized-controlled trial (RCT) to test the effects and cost effectiveness of combined interventions to address chronic malnutrition and poor child development. The arms of the trial are: (T0) existing program with monthly growth monitoring and nutritional/hygiene education; (T1) is T0 + home visits for intensive nutrition counseling within a behavior change framework; (T2) is T1 + lipid-based supplementation (LNS) for children 6-18 months old; (T3) is T2 + LNS supplementation of pregnant/lactating women; and (T4) is T1 + intensive home visiting program to support child development. There are anticipated to be n = 25 communities in each arm (n = 1250 pregnant women, n = 1250 children 0-6 months old, and n = 1250 children 6-18 months old). Primary outcomes include growth (length/height-for-age z-scores) and child development (mental, motor and social development). Secondary outcomes include care-giver reported child morbidity, household food security and diet diversity, micro-nutrient status, maternal knowledge of child care and feeding practices, and home stimulation practices. We will estimate unadjusted and adjusted intention-to-treat effects. Study protocols have been reviewed and approved by the Malagasy Ethics Committee at the Ministry of Health in Madagascar and by the institutional review board at the University of California, Davis. This study is funded by the Strategic Impact Evaluation Fund (SIEF), the World Bank Innovation Grant, the Early Learning Partnership Grant, the Japan Scaling-up for Nutrition Trustfund, and Grand Challenges Canada. The implementation of the study is financed by Madagascar's National Nutrition Office. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14393738 . Registered June 23, 2015. PMID- 27255925 TI - Dissipation of Energy by Dry Granular Matter in a Rotating Cylinder. AB - We study experimentally the dissipation of energy in a rotating cylinder which is partially filled by granular material. We consider the range of angular velocity corresponding to continous and stationary flow of the granulate. In this regime, the stationary state depends on the angular velocity and on the filling mass. For a wide interval of filling levels we find a universal behavior of the driving torque required to sustain the stationary state as a function of the angular velocity. The result may be of relevance to industrial applications, e.g. to understand the power consumption of ball mills or rotary kilns and also for damping applications where mechanical energy has to be dissipated in a controlled way. PMID- 27255924 TI - Development and validation of a classification and scoring system for the diagnosis of oral squamous cell carcinomas through confocal laser endomicroscopy. AB - BACKGROUND: Confocal laser endomicroscopy (CLE) is an optical biopsy method allowing in vivo microscopic imaging at 1000-fold magnification. It was the aim to evaluate CLE in the human oral cavity for the differentiation of physiological/carcinomatous mucosa and to establish and validate, for the first time, a scoring system to facilitate CLE assessment. METHODS: The study consisted of 4 phases: (1) CLE-imaging (in vivo) was performed after the intravenous injection of fluorescein in patients with histologically confirmed carcinomatous oral mucosa; (2) CLE-experts (n = 3) verified the applicability of CLE in the oral cavity for the differentiation between physiological and cancerous tissue compared to the gold standard of histopathological assessment; (3) based on specific patterns of tissue changes, CLE-experts (n = 3) developed a classification and scoring system (DOC-Score) to simplify the diagnosis of oral squamous cell carcinomas; (4) validation of the newly developed DOC-Score by non CLE-experts (n = 3); final statistical evaluation of their classification performance (comparison to the results of CLE-experts and the histopathological analyses). RESULTS: Experts acquired and edited 45 sequences (260 s) of physiological and 50 sequences (518 s) of carcinomatous mucosa (total: 95 sequences/778 s). All sequences were evaluated independently by experts and non experts (based on the newly proposed classification system). Sensitivity (0.953) and specificity (0.889) of the diagnoses by experts as well as sensitivity (0.973) and specificity (0.881) of the non-expert ratings correlated well with the results of the present gold standard of tissue histopathology. Experts had a positive predictive value (PPV) of 0.905 and a negative predictive value (NPV) of 0.945. Non-experts reached a PPV of 0.901 and a NPV of 0.967 with the help of the DOC-Score. Inter-rater reliability (Fleiss' kappa) was 0.73 for experts and 0.814 for non-experts. The intra-rater reliability (Cronbach's alpha) of the experts was 0.989 and 0.884 for non-experts. CONCLUSIONS: CLE is a suitable and valid method for experts to diagnose oral cancer. Using the DOC-Score system, an accurate chair-side diagnosis of oral cancer is feasible with comparable results to the gold standard of histopathology-even in daily clinical practice for non experienced raters. PMID- 27255926 TI - Trace Element Accumulation and Tissue Distribution in the Purpleback Flying Squid Sthenoteuthis oualaniensis from the Central and Southern South China Sea. AB - Sthenoteuthis oualaniensis is a species of cephalopod that is becoming economically important in the South China Sea. As, Cd, Cr, Cu, Hg, Pb, and Zn concentrations were determined in the mantle, arms, and digestive gland of S. oualaniensis from 31 oceanographic survey stations in the central and southern South China Sea. Intraspecific and interspecific comparisons with previous studies were made. Mean concentrations of trace elements analyzed in arms and mantle were in the following orders: Zn > Cu > Cd > Cr > As > Hg. In digestive gland, the concentrations of Cd and Cu exceed that of Zn. All the Pb concentrations were under the detected limit. PMID- 27255927 TI - Use of Praise and Reprimands as Critical Ingredients of Teacher Behavior Management: Effects on Children's Development in the Context of a Teacher Mediated Classroom Intervention. AB - This intervention study examined teachers' use of verbal praise and reprimands as specific components of teacher behavior management that can promote children's development in schools. The impact of teacher praise and reprimands on children's development was examined in the context of a teacher-mediated, classroom intervention. The sample involved 570 children and 30 teachers from second grade classrooms in 15 primary schools. The Good Behavior Game was implemented in half of the classrooms based on random assignment within schools. Teacher behavior management (praise for appropriate behavior and reprimands for inappropriate behavior) was observed during regular classroom lessons. Hyperactive, disruptive, and withdrawn child behavior were assessed using teacher and peer reports, global self-concept and emotional engagement were assessed using child self-reports. All variables were assessed at the beginning (pre-test) and at the end (post-test) of the school year. Multilevel regression models accounted for the nested structure of the data. The results suggested positive effects of fewer reprimands and more praise on child outcomes (except emotional school engagement), although the results differed by informant. We also found indirect effects of the Good Behavior Game (GBG) on child outcomes via teacher praise and reprimands. Overall, the study suggests that teachers' use of praise and reprimands is a malleable classroom factor that influences children's behavioral and socio-emotional development. PMID- 27255928 TI - YUCCA-mediated auxin biogenesis is required for cell fate transition occurring during de novo root organogenesis in Arabidopsis. AB - Many plant organs have the ability to regenerate a new plant after detachment or wounding via de novo organogenesis. During de novo root organogenesis from Arabidopsis thaliana leaf explants, endogenic auxin is essential for the fate transition of regeneration-competent cells to become root founder cells via activation of WUSCHEL-RELATED HOMEOBOX 11 (WOX11). However, the molecular events from leaf explant detachment to auxin-mediated cell fate transition are poorly understood. In this study, we used an assay to determine the concentration of indole-3-acetic acid (IAA) to provide direct evidence that auxin is produced after leaf explant detachment, a process that involves YUCCA (YUC)-mediated auxin biogenesis. Inhibition of YUC prevents expression of WOX11 and fate transition of competent cells, resulting in the blocking of rooting. Further analysis showed that YUC1 and YUC4 act quickly (within 4 hours) in response to wounding after detachment in both light and dark conditions and promote auxin biogenesis in both mesophyll and competent cells, whereas YUC5, YUC8, and YUC9 primarily respond in dark conditions. In addition, YUC2 and YUC6 contribute to rooting by providing a basal auxin level in the leaf. Overall, our study indicates that YUC genes exhibit a division of labour during de novo root organogenesis from leaf explants in response to multiple signals. PMID- 27255929 TI - Artificially decreased vapour pressure deficit in field conditions modifies foliar metabolite profiles in birch and aspen. AB - Relative air humidity (RH) is expected to increase in northern Europe due to climate change. Increasing RH reduces the difference of water vapour pressure deficit (VPD) between the leaf and the atmosphere, and affects the gas exchange of plants. Little is known about the effects of decreased VPD on plant metabolism, especially under field conditions. This study was conducted to determine the effects of artificially decreased VPD on silver birch (Betula pendula Roth.) and hybrid aspen (Populus tremula L.*P. tremuloides Michx.) foliar metabolite and nutrient profiles in a unique free air humidity manipulation (FAHM) field experiment during the fourth season of humidity manipulation, in 2011. Long-term exposure to decreased VPD modified nutrient homeostasis in tree leaves, as demonstrated by a lower N concentration and N:P ratio in aspen leaves, and higher Na concentration and lower K:Na ratio in the leaves of both species in decreased VPD than in ambient VPD. Decreased VPD caused a shift in foliar metabolite profiles of both species, affecting primary and secondary metabolites. Metabolic adjustment to decreased VPD included elevated levels of starch and heptulose sugars, sorbitol, hemiterpenoid and phenolic glycosides, and alpha tocopherol. High levels of carbon reserves, phenolic compounds, and antioxidants under decreased VPD may modify plant resistance to environmental stresses emerging under changing climate. PMID- 27255931 TI - The Cer-cqu gene cluster determines three key players in a beta-diketone synthase polyketide pathway synthesizing aliphatics in epicuticular waxes. PMID- 27255930 TI - Ascorbic acid accumulates as a defense response to Turnip mosaic virus in resistant Brassica rapa cultivars. AB - We initially observed that Brassica rapa cultivars containing the Turnip mosaic virus (TuMV) resistance gene, Rnt1-1, accumulated a high level of endogenous ascorbic acid (AS) and dehydroascobic acid (DHA) when infected with TuMV. We here hypothesized a possible contribution of an elevated level of AS+DHA (TAA) to the Rnt1-1-mediated resistance, and conducted a series of experiments using B. rapa and Arabidopsis plants. The application of l-galactose (the key substrate in AS synthesis) to a susceptible cultivar could increase the TAA level ~2-fold, and simultaneously lead to some degree of enhanced viral resistance. To confirm some positive correlation between TAA levels and viral resistance, we analyzed two Arabidopsis knockout mutants (ao and vtc1) in the AS pathways; the TAA levels were significantly increased and decreased in ao and vtc1 plants, respectively. While the ao plants showed enhanced resistance to TuMV, vtc1 plants were more susceptible than the control, supporting our hypothesis. When we analyzed the expression profiles of the genes involved in the AS pathways upon TuMV infection, we found that the observed TAA increase was mainly brought about by the reduction of AS oxidation and activation of AS recycling. We then investigated the secondary signals that regulate endogenous TAA levels in response to viral infection, and found that jasmonic acid (JA) might play an important role in TAA accumulation. In conclusion, we reason that the elevated TAA accumulation in B. rapa plants would be at least partly mediated by the JA-dependent signaling pathway and may significantly contribute to viral resistance. PMID- 27255934 TI - [Dialogical principle in patient interaction]. PMID- 27255932 TI - Drosophila cells use nanotube-like structures to transfer dsRNA and RNAi machinery between cells. AB - Tunnelling nanotubes and cytonemes function as highways for the transport of organelles, cytosolic and membrane-bound molecules, and pathogens between cells. During viral infection in the model organism Drosophila melanogaster, a systemic RNAi antiviral response is established presumably through the transport of a silencing signal from one cell to another via an unknown mechanism. Because of their role in cell-cell communication, we investigated whether nanotube-like structures could be a mediator of the silencing signal. Here, we describe for the first time in the context of a viral infection the presence of nanotube-like structures in different Drosophila cell types. These tubules, made of actin and tubulin, were associated with components of the RNAi machinery, including Argonaute 2, double-stranded RNA, and CG4572. Moreover, they were more abundant during viral, but not bacterial, infection. Super resolution structured illumination microscopy showed that Argonaute 2 and tubulin reside inside the tubules. We propose that nanotube-like structures are one of the mechanisms by which Argonaute 2, as part of the antiviral RNAi machinery, is transported between infected and non-infected cells to trigger systemic antiviral immunity in Drosophila. PMID- 27255933 TI - Fludeoxyglucose positron emission tomography-computed tomography scan showing polyarthritis in a patient with an atypical presentation of Henoch-Schonlein vasculitis without clinical signs of arthritis: a case report. AB - BACKGROUND: Henoch-Schonlein vasculitis is the most common systemic vasculitis in children. Arthritis or arthralgia occurs in 80 % of patients. We believe this to be the first case report to describe the finding of polyarthritis in a fludeoxyglucose positron emission tomography-computed tomography scan in a patient with Henoch-Schonlein vasculitis without clinical signs of arthritis. CASE PRESENTATION: A 4.5-year-old Caucasian boy presented with fever of 4 days' duration followed by debilitating migratory arthralgia and inflammation. He underwent a fludeoxyglucose positron emission tomography-computed tomography scan to exclude a possible malignant cause or to detect any infectious or autoimmune focus of his symptoms. Fludeoxyglucose uptake was observed in multiple large joints and in multiple tendons. These findings suggested active polyarthritis and polytendinitis. However, physical and ultrasound evaluations did not show any signs of arthritis in our patient, despite his evident arthralgia. CONCLUSIONS: Fludeoxyglucose positron emission tomography-computed tomography might be able to detect inflammatory activity in painful joints that cannot yet be detected clinically or with ultrasound evaluation in a patient with Henoch-Schonlein vasculitis. Therefore, fludeoxyglucose positron emission tomography-computed tomography can be of additional value in the diagnostic workup of patients with an unresolved diagnosis of suspected autoimmune disease, especially in patients with unresolved arthralgia and fever of unknown cause. PMID- 27255935 TI - Fetishes and factishes: Durkheim and Latour. AB - This paper defends the concept of 'fetishism' as an explanatory parameter in sociological theorizing on Durkheimian grounds, while at the same time paying due attention to important insights regarding the role of objects in social life, originating from Actor-Network Theory (ANT). It critically assesses the current critique of the concept of fetishism propagated by ANT protagonist Bruno Latour. Latour and suggests a compromise between these two 'schools'. First, to place the paper firmly in context, I analyse some examples of modern fetishism and outline the themes of the ensuing discussion. Next, I turn to Durkheim, seeking to develop a distinct interpretation of the concept of the social and of fetishism, and then point to some of Durkheim's shortcomings and attempt to make room for Latourian perspectives. Finally, I critically assess Latour's dismissal of forms of social 'explanation' and of the concept of fetishism. PMID- 27255936 TI - Specialization of the motor system in infancy: from broad tuning to selectively specialized purposeful actions. AB - In executing purposeful actions, adults select sufficient and necessary limbs. But infants often move goal-irrelevant limbs, suggesting a developmental process of motor specialization. Two experiments with 9- and 12-month-olds revealed gradual decreases in extraneous movements in non-acting limbs during unimanual actions. In Experiment 1, 9-month-olds produced more extraneous movements in the non-acting hand/arm and feet/legs than 12-month-olds. In Experiment 2, analysis of the spatiotemporal dynamics of infants' movements revealed developmental declines in the spatiotemporal coupling of movements between acting and non acting arms. We also showed that the degree of specialization in infants' unimanual actions is associated with individual differences in motor experience and visual attention, indicating the experience-dependent and broad functional nature of these developmental changes. Our study provides important new insights into motor development: as in cognitive domains, motor behaviours are initially broadly tuned to their goal, becoming progressively specialized during the first year of life. PMID- 27255937 TI - Effects of Untreated Periodontitis on Osseointegration of Dental Implants in a Beagle Dog Model. AB - BACKGROUND: There have been previous studies on the relationship between periodontitis and peri-implantitis, but limited information is available on how periodontitis affects osseointegration and wound healing of newly placed dental implants adjacent to natural teeth. The objective of the present experiment is to evaluate healing around dental implants adjacent to teeth with untreated experimental periodontitis. METHODS: The study included six male beagle dogs. Scaling and plaque control procedures were performed on three dogs (control group). In the other three dogs (experimental group), retraction cords and ligature wires were placed subgingivally around all premolars and the first molars. Induced experimental periodontitis was confirmed after 3 months. Each control or experimental group was divided into two subgroups depending on the timing of implant placement (immediate/delayed). Twelve dental implants (two implants for each dog) were placed immediately, and the other 12 dental implants (two implants for each dog) were placed 2 months after extraction. The animals were sacrificed 2 months after implant placement. Histologic and histometric analyses were performed. RESULTS: Four implants (three from the immediate placement group and one from the delayed placement group) failed in the experimental group. There were significant differences in the percentage of bone to-implant contact and marginal bone volume density between the control and experimental groups. Both parameters were significantly lower in the experimental group than in the control group (P <0.05). There was a tendency toward more marginal bone loss in the experimental group than the control group. CONCLUSIONS: Immediate placement of implants is associated with a higher failure rate compared with delayed placement. Untreated experimental periodontitis was correlated with compromised osseointegration in the implants with delayed placement. PMID- 27255938 TI - Civilian Airway Trauma: A Single-Institution Experience. AB - BACKGROUND: Injuries to the airway in the neck and thorax are uncommon, but may be potentially life threatening. The objective of this study is to determine the clinical characteristics and outcomes for patients with airway injury. METHODS: From 1974 to 2014, a prospectively entered trauma database at a Level 1 trauma center was accessed to identify patients with injuries to the larynx, cervical trachea, or thoracic airway. Hospital charts were reviewed to obtain data on demographics, presentation, injury management, in-hospital and long-term morbidity and in-hospital mortality. Multivariate logistic regression was used to estimate predictors of mortality and long-term vocal cord morbidity. Data are expressed as N (%). RESULTS: One hundred and twenty patients were included (median injury severity score: 19 [interquartile range: 10-27]). There were 65 (54 %) blunt and 55 (46 %) penetrating injuries, with 90 (75 %) suffering multiple injuries. Sixteen (13 %) patients died from associated injuries (7: in ER; 9: after admission). Injuries were located in the cervical airway [101 (84 %)], thoracic airway [21 (18 %)], or both [2 (2 %)]. Eighty-six (72 %) patients were managed surgically. Predictors of in-hospital mortality included hemodynamic instability (OR 6.54, 95 % CI 1.11-37.14), GCS < 8 upon presentation (OR 4.35, 95 % CI 3.24-5.41), and head trauma (OR 4.10, 95 % CI 1.91-6.30). Fracture of cricoid or thyroid cartilages was a strong predictor of long-term vocal cord injury (OR 3.93, 95 % CI 1.25-12.59). CONCLUSIONS: Airway trauma remains a major challenge for early diagnosis, airway control, and management of both acute life threatening injury and long-term morbidity. PMID- 27255939 TI - Orthopedic Activity in Field Hospitals Following Earthquakes in Nepal and Haiti : Variability in Injuries Encountered and Collaboration with Local Available Resources Drive Optimal Response. AB - BACKGROUND: Field hospitals have been deployed by the Israel Defense Forces (IDF) Medical Corps in numerous disaster events. Two recent deployments were following earthquakes in Haiti in 2010 and in Nepal in 2015. Despite arrival in similar timetables, the mode of operation was different-independently in Haiti and in collaboration with a local hospital in Nepal. The pathology encountered in the two hospitals and the resultant treatment requirements were significantly different between the two events. The purpose of this study was to analyze these differences and their implications for preparation and planning of future deployments. METHODS: Data were obtained from IDF records and analyzed using SPSSTM software. RESULTS: 1686 patients were treated in Nepal versus 1111 in Haiti. The caseload in Nepal included significantly less earthquake-related injuries (26 vs. 66 %) with 28 % of them sustaining fractures versus 47 % in Haiti. Femoral fractures accounted for 7.9 % of fractures in Nepal versus 26.4 % in Haiti with foot fractures accounting for 23.8 and 6.4 %, respectively. The rate of open fracture was similar at 29.4 % in Nepal and 27.5 % in Haiti. 18.1 % of injured patients in Nepal underwent surgery, and 32.9 % of which was skeletal compared to 32 % surgical cases (58.8 % skeletal) in Haiti. 74.2 % of patients in Nepal and 34.3 % in Haiti were treated for pathology unrelated to the earthquake. CONCLUSIONS: The reasons for the variability in activities between the two hospitals include the magnitude of the disaster, the functionality of the local medical system which was relatively preserved in Nepal and destroyed in Haiti and the mode of operation which was independent in Haiti and collaborative with a functioning local hospital in Nepal. Emergency medical teams (EMTs) may encounter variable caseloads despite similar disaster scenarios. Advance knowledge of the magnitude of the disaster, the functionality of the local medical system, and the collaborative possibilities will help in planning and preparing EMTs to function optimally and appropriately. However, as this information will often be unavailable, EMTs should be capable to adapt to unexpected conditions. PMID- 27255940 TI - Significant Improvement in Outcomes of Patients with Intrahepatic Cholangiocarcinoma after Surgery. AB - BACKGROUND: The prognosis of intrahepatic cholangiocarcinoma (ICC) remains poor despite improvements in treatment and post-operative clinical management. We review our experiences and evaluate our current surgical approaches by comparing patients from two consecutive treatment periods. METHODS: One hundred forty-four patients who underwent hepatectomy for ICC between 1993 and 2014 were divided into groups that received treatment before (n = 65, first period) and after 2006 (n = 79, second period), when new treatment options such as adjuvant chemotherapy and multimodal therapy for recurrence were introduced. Clinicopathological characteristics and survival outcomes were compared between the groups. RESULTS: First-period patients exhibited more advanced tumor characteristics, including larger tumors, higher serum carbohydrate antigen 19-9 levels, and vascular invasion. Median overall survival (OS) durations of the first- and second-period groups were 21.4 and 57.7 months, respectively (p < 0.001); corresponding median disease-free survival (DFS) durations were 12.2 and 16.6 months, respectively (p = 0.027). Multivariate analysis found an independent association of the treatment time period with OS and DFS. Notably, second-period patients with N1 disease achieved a longer OS and DFS (median OS time: 12.4 and 26.0 months, p = 0.0018, and median DFS: 4.7 and 10.7 months p = 0.019, respectively). Among recurrent patients (first, n = 50 and second, n = 44), second-period patients had a significantly longer survival after recurrence (8.0 vs. 22.3 months, p < 0.001). CONCLUSION: ICC patients, particularly those with N1 disease, achieved significant survival improvements that were partly attributable to patient selection, adjuvant chemotherapy, and multimodal treatment after recurrence. PMID- 27255941 TI - Perioperative Mortality Rates in Australian Public Hospitals: The Influence of Age, Gender and Urgency. AB - INTRODUCTION: A decline in surgical deaths has been observed in Australia since the introduction of the Australian and New Zealand Audit of Surgical Mortality (ANZASM). The current study was conducted to determine whether the perioperative mortality rate (POMR) has also declined. METHODS: This study is a retrospective review of the POMR for surgical procedures in Australian public hospitals between July 2009 and June 2013, using data obtained from the Australian Institute of Health and Welfare. Operative procedures contained in the Australian Refined Diagnosis Related Groups were selected and the POMR was modelled using urgency of admission, age and gender as explanatory covariates. RESULTS: The POMR in Australian public hospitals reduced by 15.4 % over the 4-year period. The emergency admissions POMR dropped from 1.40 to 1.12 %, and the elective admissions POMR from 0.09 to 0.08 %. The binary logistic regression model used to predict patient mortality showed emergency admissions to have a higher POMR than elective, being more evident at older ages. For emergency admissions, the difference in POMR between females and males increased with age, from about 55 years onwards, with females being lower. For elective surgeries, the difference between males and females was of little practical importance across ages. CONCLUSIONS: The reduction in the POMR in Australia confirms the reduction in surgical deaths reported to ANZASM. Continuing to monitor POMR will be important to ensure the safest surgery in Australia. Further investigations into case-mix will allow better risk adjustment and comparison between regions and time periods, to facilitate continuous quality improvement. PMID- 27255942 TI - Outcomes of Percutaneous Cholecystostomy for Acute Cholecystitis. AB - BACKGROUND: Acute cholecystitis (AC) is an important cause of emergency admissions among the elderly. The use of percutaneous cholecystostomy (PC) as bridging therapy among high-risk patients is widely accepted. However, the use of PC as definitive treatment is controversial. AIM: To determine the characteristics, clinical outcomes and predictors of recurrence of AC among patients who underwent PC. METHODS: A retrospective case series of 71 consecutive patients [73 (38-96) years, 43/71 males] treated with PC for AC at a tertiary hospital from 2007 to 2013, with data collected from case records. RESULTS: Patients were followed up for 37.0 (0.1-110.8) months after PC. Mortality rate was 8.5 % (6/71) during the index admission and 32.4 % (23/71) at the end of follow-up. Recurrence rate for AC was 11.9 % (7/59). Median time to recurrence was 62 (13-464) days. PC was definitive treatment in 33/59. Predictors of recurrence were higher serum alkaline phosphatase (ALP) at diagnosis (OR = 1.01, 95 % CI 1.00-1.02, p = 0.021) and acute myocardial infarction (AMI) during index admission (OR = 8.00, 95 % CI 1.19-54.0, p = 0.033). Fifteen patients (26.3 %, 15/71) had post-procedural complications including dislodgement (14 %, 10/71), tube obstruction (7.0 %, 5/71), bile leaks (2.8 %, 2/71), gallbladder perforation (1.4 %, 1/71), bowels perforation (1.4 %, 1/71) and severe post-procedural haemorrhage (1.4 %, 1/71). CONCLUSION: PC is effective and relatively safe in high-risk patients with AC. However, patients with higher ALP or AMI during index admission have higher risk of recurrence and might benefit from definitive cholecystectomy. PMID- 27255943 TI - Prognostic Analysis of Surgical Resection for Pulmonary Metastasis from Hepatocellular Carcinoma. AB - INTRODUCTION: Pulmonary metastases are the most common among extrahepatic recurrences from hepatocellular carcinoma (HCC). It causes high risk of HCC related death, despite recent progress in therapeutic options. However, a role of pulmonary metastasectomy as well as prognostic factors after metastasectomy has not been well established. We aimed to investigate survival outcomes and prognostic factors after pulmonary resection for metastases from HCC. METHODS: A series of 93 patients who underwent pulmonary resections for metastases from HCC between June 1990 and July 2013 from multi-institutional database were retrospectively evaluated. Perioperative clinicopathological data and their association with prognosis were investigated. RESULTS: Of 93 patients, 77 had one pulmonary metastasis, and 16 had two or more. Recurrence after pulmonary resection was noted in 60 patients (64.5 %). The estimated 5-year overall survival rate was 41.4 % with median survival time after pulmonary metastatectomy of 39.0 months. Univariate prognostic analysis showed that disease-free interval of >=12 months was significantly associated with favorable outcomes in both overall survival (5-year rate, 59.3 vs. 28.7 %, p = 0.026) and disease-specific survival (5-year rate, 62.5 vs. 36.2 %; p = 0.038) after pulmonary metastatectomy. A multivariate analysis revealed that disease-free interval was an independent prognostic factor (HR = 2.020, 95 % CI, 1.069-3.816, p = 0.030). CONCLUSION: We have shown that a disease-free interval was an independent prognostic factor in patients who underwent pulmonary resection for metastasis from HCC. Also, pulmonary metastasectomy can be one of the therapeutic choices for select patients. PMID- 27255944 TI - Androgen receptor splice variant 7 in castration-resistant prostate cancer: Clinical considerations. AB - Constitutively-active ligand-independent splice variants of the androgen receptor are an adaptive response by prostate cancer cells to escape androgen deprivation therapy and novel androgen receptor-directed treatments. Androgen receptor splice variant 7 is the most common splice variant detected in clinical biospecimens, and emerging data now suggest that the presence of tumoral androgen receptor splice variant 7 might be indicative of primary and acquired resistance to next generation androgen pathway inhibitors, such as abiraterone and enzalutamide. At the same time, taxane chemotherapy might retain its efficacy regardless of androgen receptor splice variant 7 status, thus suggesting the potential for a predictive biomarker guiding treatment selection in men with metastatic castration-resistant prostate cancer. Herein, we review the preclinical data elucidating the structure and function of androgen receptor splice variant 7, we describe the existing clinical data using this biomarker in metastatic castration resistant prostate cancer, and we highlight potential therapeutic strategies to target androgen receptor splice variant 7-expressing prostate cancer. PMID- 27255945 TI - Up-Regulation of SIRT1 Reduces Endoplasmic Reticulum Stress and Renal Fibrosis. AB - BACKGROUND: Endoplasmic reticulum (ER) stress is emerging as an important factor in the development of organ fibrosis. Therefore, modulation of ER stress may serve as one of the possible therapeutic approaches to renal fibrosis. SIRT1, a class III histone deacetylase, has been found to exert beneficial effects in kidney diseases. However, it is largely unknown whether and how SIRT1 suppresses the ER stress. We postulated that upregulation of SIRT1 would suppress the ER stress through induction of heme oxygenase-1 (HO-1) and thioredoxin. METHODS: HK 2 tubular cells, experimental mouse models of tunicamycin (TM)-induced ER stress and unilateral ureteral obstruction (UUO) were used. Expression of ER stress induced protein was measured by Western blot analysis and immunohistochemical staining. ER stress was induced by chemical ER stress inducers [TM [,]thapsigargin (TG)] and non-chemical inducers such as angiotensin II, aldosterone, high glucose and albumin. RESULTS: SIRT1 activator (SRT1720) induced SIRT1 expression in a time- and dose-dependent manner in HK-2 cells. SRT1720 suppressed the TM- or TG-induced ER stress, as shown by inhibition of TM- or TG induced upregulation of glucose-related protein 78 (GRP78), phosphor-specific eukaryotic translation initiation factor-2alpha and C/EBP homologous protein through HO-1 and thioredoxin, which were abolished by pretreatment with SIRT1 inhibitor (sirtinol). SRT1720 also suppressed the ER stress induced by angiotensin II, aldosterone, high glucose and albumin. In animal studies, treatment with SRT1720 reduced the tubular expression of GRP78 and increased the expression of HO-1 and thioredoxin. SRT1720 also reduced the UUO-induced renal fibrosis. CONCLUSION: SIRT1 may serve as a promising therapeutic target by reducing ER stress and fibrosis. PMID- 27255946 TI - Post-refractive surgery complications and eye disease, active component, U.S. Armed Forces, 2005-2014. AB - Refractive surgery (RS) is a common procedure in the U.S. military population. This report provides an estimation of incident RS for vision correction purposes in the active component of the U.S. military from 1 January 2005 through 31 December 2014 and the prevalence of post-RS complications and eye disease in the 1-year period after RS. During the surveillance period, a total of 121,571 subjects without a diagnosis of eye disease other than hyperopia, myopia, or astigmatism in the previous year received a single incident RS procedure. In the 1-year period after RS, 5.3% of subjects with preoperative hyperopia or myopia had treatment-persistent (unresolved) hyperopia or myopia; 2.0% of subjects with preoperative astigmatism had treatment-persistent (unresolved) astigmatism; and 3.8% were diagnosed with tear film insufficiency. In general, most outcomes showed higher prevalences in Army and Air Force personnel versus Navy and Marine Corps personnel, in women versus men, in officer versus enlisted personnel, and in aviation and Special Forces personnel. A wide variation in outcome prevalences was noted by procedural military treatment facility. PMID- 27255947 TI - Update: Urinary stones, active component, U.S. Armed Forces, 2011-2015. AB - Urinary stones can cause debilitating morbidity that impairs the operational effectiveness of affected members of the U.S. Armed Forces. This report documents that, during the past 5 years, rates of incident diagnoses of urinary stones decreased by about 17% in the active component of the U.S. military. During the period, annual rates of inpatient diagnosed cases were low and relatively stable, while rates of outpatient diagnosed cases slightly decreased. Incidence rates were slightly higher among females than males in 2011; however, rates were very similar among males and females from 2012 through 2015. Rates of incident diagnoses among white, non-Hispanic and Native American/Alaska Native service members were consistently 80%-100% higher than among black, non-Hispanic and Asian/Pacific Islander service members and 35%-45% higher than among Hispanic and "other race/ethnicity" service members. During the 5-year period, a total of 3,350 service members received more than one incident diagnosis of urinary stones ("recurrent cases"); one-tenth (10.2%) of all incident cases during the period were recurrent cases. Service members with histories of urinary stones should be counseled and closely supervised to avoid dehydration and to adhere to diets that reduce the risk of stone formation. PMID- 27255948 TI - Surveillance snapshot: Zika virus infection among Military Health System beneficiaries following introduction of the virus into the Western Hemisphere, 20 May 2016. PMID- 27255949 TI - Surveillance snapshot: Department of Defense Global, Laboratory-Based Influenza Surveillance Program, 2014-2015 season. PMID- 27255950 TI - Seasonal changes and spatial distributions of nonylphenol ethoxylates in sewage treatment plant with BAF process. AB - Recently, there has been growing concern over the prevalence of Nonylphenol ethoxylates (NPnEOs) in the natural environment as these compounds are known endocrine disruptors. This study focuses on the seasonal variation and spatial distribution of NPnEOs in the wastewater of a full scale sewage treatment plant, operating a Biological Aerated Filter (BAF), in Harbin, a city in Northeast China. Water samples were collected seasonally from 2009 to 2010, with the findings revealing remarkable seasonal variations in the concentrations of NPnEOs. The total influent concentrations of short-chain NPnEOs (NP, NP1EO and NP2EO) measured during winter was 16 mg L-1, with decreasing concentrations observed during autumn, summer and spring of 89, 67 and 41 mg L-1, respectively. The concentrations of the short-chain NPnEOs measured during autumn become higher (89 mg L-1), with summer becoming the lowest (16 mg L-1). Although the removal efficiencies of short-chain NPnEOs in STP showed various trends in different seasons, they all achieve relatively good performance during summer and winter. The BAF process plays the main role in the elimination of short-chain NPnEOs compounds; however, the ambient temperatures were not found to significantly influence the removal efficiency of short-chain NPnEOs compounds from the STP. PMID- 27255952 TI - Acute respiratory compromise on inpatient wards in the United States: Incidence, outcomes, and factors associated with in-hospital mortality. AB - AIM: To estimate the United States' incidence and in-hospital mortality of acute respiratory events on inpatient wards and to identify factors associated with mortality. METHODS: This is an analysis of prospectively collected data from the Get With the Guidelines((r)) - Resuscitation registry. We included adult patients with index acute respiratory events on inpatient wards from January 2005 to December 2013. A negative binomial regression model was used to estimate the 2012 United States incidence and a multivariable logistic regression model was used to examine time trends and characteristics associated with in-hospital mortality. RESULTS: There were 13,086 index events from 320 hospitals included in the analysis. Using 2012 data, the estimated number of events in the United States was 44,551 (95%CI: 25,170-95,371). The in-hospital mortality for the entire cohort was 39.4% (95%CI: 38.5, 40.2) and rose to 82.6% (95%CI: 79.9, 85.2) for events leading to cardiac arrest. There was a decrease in in-hospital mortality over time (48.3% in 2005 to 34.5% in 2013, p<0.001). Characteristics associated with mortality included agonal breathing, hypotension and septicemia. CONCLUSIONS: Acute respiratory events on inpatient wards in the US is common with an associated in-hospital mortality of approximately 40% that has been decreasing over the past decade. Multiple factors were associated with in-hospital mortality. PMID- 27255951 TI - Intermolecular biparatopic trapping of ErbB2 prevents compensatory activation of PI3K/AKT via RAS-p110 crosstalk. AB - Compensatory mechanisms, such as relief of AKT-ErbB3-negative feedback, are known to desensitize ErbB2-dependent tumours to targeted therapy. Here we describe an adaptation mechanism leading to reactivation of the PI3K/AKT pathway during trastuzumab treatment, which occurs independently of ErbB3 re-phosphorylation. This signalling bypass of phospho-ErbB3 operates in ErbB2-overexpressing cells via RAS-PI3K crosstalk and is attributable to active ErbB2 homodimers. As demonstrated by dual blockade of ErbB2/RAS and ErbB3 by means of pharmacological inhibition, RNA interference or by specific protein binders obstructing the RAS p110alpha interaction, both routes must be blocked to prevent reactivation of the PI3K/AKT pathway. Applying these general principles, we developed biparatopic designed ankyrin repeat proteins (DARPins) trapping ErbB2 in a dimerization incompetent state, which entail pan-ErbB inhibition and a permanent OFF state in the oncogenic signalling, thereby triggering extensive apoptosis in ErbB2 addicted tumours. Thus, these novel insights into mechanisms underlying network robustness provide a guide for overcoming adaptation response to ErbB2/ErbB3 targeted therapy. PMID- 27255953 TI - Alterations in cognitive outcome between 3 and 12 months in survivors of out-of hospital cardiac arrest. AB - OBJECTIVES: To prospectively investigate cognitive recovery from 3 to 12 months after resuscitation from out-of-hospital cardiac arrest (OHCA) and the associations between cognitive performance at 3 months and health-related quality of life (HRQL), psychological distress and work status after 12 months. METHODS: At both assessments, neuropsychological tests were used to measure aspects of general mental ability, verbal and visual memory, psychomotor speed and executive function. The Short Form-36 (SF-36) was used to measure mental and physical HRQL, and the Hospital Anxiety and Depression Scale (HADS) to assess psychological distress. RESULTS: 33 survivors completed both exams (31 males, mean age 58.6 years, SD=13). The OHCAs were witnessed and due to cardiac origins. Nine patients were awake at admission to the hospital. Longer coma duration was associated with poorer cognitive results. Memory impairments were the most common symptom. The mean changes and effect sizes indicated minor improvements in cognitive performance from 3 to 12 months (Hedges g<=.26). Reliable change indices for an individual's results further confirmed the stability of the group statistics. The HADS scores showed increased depressive symptoms, and mental HRQL was reduced from 3 to 12 months. Higher reports of psychological distress were related to worse HRQL. Work participation increased. Better cognitive results at 3 months were correlated with better HRQL and return to work at 12 months. CONCLUSIONS: The current data describe stability in results from 3 to 12 months. A worse cognitive performance at 3 months and higher reports of psychological distress were associated with lower HRQL. PMID- 27255954 TI - Endotracheal suction in term non vigorous meconium stained neonates-A pilot study. AB - AIM: To evaluate the effect of 'No endotracheal suction' on occurrence of meconium aspiration syndrome (MAS) and/or all-cause mortality in non-vigorous neonates born through meconium stained amniotic fluid (MSAF). METHODS: This pilot randomized controlled trial enrolled term non-vigorous neonates (>=37 weeks) born through MSAF. Neonates randomized to 'No Endotracheal suction group' ('No ET' Group; n=88) did not undergo endotracheal suction before the definitive steps of resuscitation. Neonates randomized to 'Endotracheal suction group' ('ET' Group; n=87) underwent tracheal suction as part of the initial steps as per the current NRP recommendations. The primary outcome was occurrence of MAS and/or death. Secondary outcome variables were duration and severity of respiratory distress, need for respiratory support, development of hypoxic ischemic encephalopathy (HIE) and duration of oxygen therapy and hospitalization. RESULTS: Baseline characters including birth weight and gestational age were similar between the two groups. MAS was present in 23 (26.1%) vs. 28 (32.2%) neonates in 'No ET' and 'ET' groups respectively (OR 0.4 (0.12-1.4); p=0.14) with 4 (4.6%) and 9 (10.34%) deaths amongst these neonates with MAS in respective groups (OR 0.75 (0.62-1.2); p=0.38). Other parameters like severity and duration of respiratory distress, need for respiratory support, incidence of HIE, duration of oxygen therapy and duration of hospitalization were comparable. CONCLUSION: This study demonstrates that it is feasible to randomize non-vigorous infants born through meconium stained liquor to receive on not receive endotracheal suction. There is a need for a multi-center trial to address whether the current practices and guidelines can be justified. PMID- 27255955 TI - HEMS advanced trauma team retrieval of a patient with accidental hypothermic cardiac arrest for ECMO therapy. PMID- 27255956 TI - An intervention for cardiac arrest survivors with chronic fatigue: A feasibility study with preliminary outcomes. AB - AIM: The primary aim was to examine the feasibility of recruiting and retaining participants for an Energy Conservation+Problem Solving Therapy (EC+PST) intervention delivered over the telephone, to evaluate the acceptability of the intervention, and to assess the appropriateness of the outcome measures. The secondary aim was to evaluate the preliminary intervention effect on fatigue impact, activity performance, and participation in daily activities in post cardiac arrest (CA) adults with chronic fatigue. METHODS: This feasibility study used a prospective, pre-post experimental design. Individuals who were at least 3 months post-CA with moderate-to-severe fatigue were eligible to participate. By participating in EC+PST intervention sessions, participants learned how to apply EC strategies to solve their fatigue-related problems. Participants were assessed before and after completing the intervention using outcome measures assessing fatigue, activity performance, and participation in daily activities. RESULTS: Eighteen CA survivors with chronic fatigue successfully completed the intervention and the assessments with high satisfaction. We observed a 15% recruitment rate and ceiling effects on two outcome measures of perceived performance in daily activities. Significant decreases in the impact of physical (p=.001) and cognitive (p=.006) fatigue of CA survivors were observed with small to moderate effect sizes of r=0.23-0.25 after receiving the EC+PST intervention. CONCLUSION: The delivery of EC+PST intervention over the telephone is feasible, and the intervention is highly acceptable to CA survivors with chronic fatigue. Also, the EC+PST intervention seems promising in reducing the impact of physical and cognitive fatigue of CA survivors. PMID- 27255957 TI - Using the relationship between brain tissue regional saturation of oxygen and mean arterial pressure to determine the optimal mean arterial pressure in patients following cardiac arrest: A pilot proof-of-concept study. AB - INTRODUCTION: Prospectively assess cerebral autoregulation and optimal mean arterial pressure (MAPOPT) using the dynamic relationship between MAP and regional saturation of oxygen (rSO2) using near-infrared spectroscopy. METHODS: Feasibility study of twenty patients admitted to the intensive care unit following a cardiac arrest. All patients underwent continuous rSO2 monitoring using the INVOS((r)) cerebral oximeter. ICM+((r)) brain monitoring software calculates the cerebral oximetry index (COx) in real-time which is a moving Pearson correlation coefficient between 30 consecutive, 10-s averaged values of MAP and correspond rSO2 signals. When rSO2 increases with increasing MAP (COx >=0.3), cerebral autoregulation is dysfunctional. Conversely, when rSO2 remains constant or decreases with increasing MAP (COx <0.3), autoregulation is preserved. ICM+((r)) fits a U-shaped curve through the COx values plotted vs. MAP. The MAPOPT is nadir of this curve. RESULTS: The median age was 59 years (IQR 54-67) and 7 of 20 were female. The cardiac arrest was caused by myocardial infarction in 12 (60%) patients. Nineteen arrests were witnessed and return of spontaneous circulation occurred in a median of 15.5min (IQR 8-33). Patients underwent a median of 30h (IQR 23-46) of monitoring. COx curves and MAPOPT were generated in all patients. The mean overall MAP and MAPOPT were 76mmHg (SD 10) and 76mmHg (SD 7), respectively. MAP was outside of 5mmHg from MAPOPT in 50% (SD 15) of the time. Out of the 7672 5-min averaged COx measurements, 1182 (15%) were at 0.3 or above, indicating absence of autoregulation. Multivariable polynomial fractional regression demonstrated an increase in COx with increasing temperature (P=0.008). CONCLUSIONS: We demonstrated the feasibility to determine a MAPOPT using cerebral oximetry in patients after cardiac arrest. PMID- 27255958 TI - The amyloid cascade hypothesis: are we poised for success or failure? AB - The first description of Alzheimer's disease (AD) was made in 1907 by Alois Alzheimer (Allgemeine Zeitschrift fur Psyciatrie und Psychisch-Gerichtliche Medizin 64, 3, 1907), although other contemporary physicians had made similar, and rather more complete, assessments of the neuropathological changes present in the AD brain (Fischer, Monatsschr Psychiat Neurol 22, 17, 1907). Our knowledge of AD has increased dramatically and continues to accelerate. This year is 25 years after the publication of a series of papers that, in various ways, articulated the amyloid cascade hypothesis (ACH) for AD (Beyreuther and Masters, Brain Pathol 1, 241-251, 1991; Hardy and Allsop, Trends Pharmacol Sci 12, 383-388, 1991; Selkoe, Neuron 6, 487-498, 1991; Hardy and Higgins, Science 256, 184-185, 1992). This review will cover some familiar territory, but we shall also place the ACH into a wider context, compare it with other hypotheses for AD, explore the evolution of the hypothesis to encompass new findings, and determine, irrespective of the merits of the hypothesis itself, whether it has been useful for the research field, both in academia and in industry. Finally, we shall review how the ACH has led to a number of therapeutic approaches, all of which have, to date, failed to reach their primary efficacy end-points in clinical trials and reflect upon what the future may hold. We review the amyloid cascade hypothesis (ACH) and compare it with other hypotheses that have been posited to explain the initiation and progression Alzheimer's disease. We document the data that support the ACH, and also reflect upon its deficiencies. We list the recent clinical failures of amyloidocentric drugs and anticipate the results that new therapeutic approaches may deliver. This article is part of the 60th Anniversary special issue. PMID- 27255959 TI - Attitudes, practice, and experience of German dentists regarding repair restorations. AB - OBJECTIVES: The aim of the present study was to perform a representative survey among German dentists about attitudes, practice, and experience regarding single tooth repair restorations. MATERIALS AND METHODS: An anonymous questionnaire was designed and mailed to all registered dentists in Lower Saxony (n = 6600). Twenty eight percent were returned (n = 1852), and n = 1805 could be analyzed. Statistical analyses were done by Wilcoxon signed-rank tests, Kruskal-Wallis tests, and ordered logistic regressions (p < 0.05). RESULTS: Only 2.2 % of the dentists declared to never perform repair restorations. Composite restorations were repaired significantly more often than all other materials. Frequency of performing repair restorations was partially associated to dentist-related factors. The decision for repairing a restoration was dependent on several tooth- and restoration-associated variables. The main indications for repair were the partial loss of restoration or adjacent tooth structure as well as chipping and endodontic access cavities of crowns. Repair restorations were mostly done with composite using various different preconditioning techniques. Overall patients' acceptance was reported to be high. Most of the dentists considered repair restorations as permanent restoration with a moderate to high longevity. Estimated success of repair restorations depended significantly on the dentists' experiences (frequency and techniques of repair restorations). CONCLUSIONS: Repair restorations were often performed and were well accepted by dentists and patients, but indications for repair restorations as well as applied materials and techniques varied distinctly. CLINICAL RELEVANCE: Repairs of single-tooth restorations are well accepted and frequently performed, but indications, techniques, and materials require further research. PMID- 27255960 TI - Scaling of morphogenetic patterns in reaction-diffusion systems. AB - Development of multicellular organisms is commonly associated with the response of individual cells to concentrations of chemical substances called morphogens. Concentration fields of morphogens form a basis for biological patterning and ensure its properties including ability to scale with the size of the organism. While mechanisms underlying the formation of morphogen gradients are reasonably well understood, little is known about processes responsible for their scaling. Here, we perform a formal analysis of scaling for chemical patterns forming in continuous systems. We introduce a quantity representing the sensitivity of systems to changes in their size and use it to analyse scaling properties of patterns forming in a few different systems. Particularly, we consider how scaling properties of morphogen gradients forming in diffusion-decay systems depend on boundary conditions and how the scaling can be improved by passive modulation of morphogens or active transport in the system. We also analyse scaling of morphogenetic signal caused by two opposing gradients and consider scaling properties of patterns forming in activator-inhibitor systems. We conclude with a few possible mechanisms which allow scaling of morphogenetic patterns. PMID- 27255961 TI - Headache Induced by Fibrous Dysplasia of the Sphenoid Sinus: A Case Report. AB - Although is a rare disease entity and it is not enough to know about the causal relationship between fibrous dysplasia (FD) of the sphenoid sinus and headache, we should keep in mind the headache is the most common symptom among wide spectrum of potential symptoms in craniofacial FD. PMID- 27255962 TI - Correction. PMID- 27255963 TI - Correction. PMID- 27255964 TI - Correction. PMID- 27255965 TI - Rate-Dependent Exit Conduction Block From Pulmonary Vein to Left Atrium After Entrance Block: New Implications of Pacing Rate to Confirm Bidirectional Conduction Block. PMID- 27255967 TI - Pretreatment thrombocytosis predicts survival in colorectal cancer. PMID- 27255966 TI - The Prevalence and Significance of the Early Repolarization Pattern in Sudden Arrhythmic Death Syndrome Families. AB - BACKGROUND: The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear. METHODS AND RESULTS: We analyzed 12-lead ECGs of 401 first-degree relatives of individuals who had died from SADS. The prevalence of ER patterns was compared with family clustered controls. ER was more common in SADS family members than in controls (21% versus 8%; odds ratio: 5.14; 95% confidence interval, 3.37-7.84) independent of the presence of a familial cardiac diagnosis. Both ascending and horizontal ER patterns were more common. In addition, ER was investigated for associations with findings from ajmaline provocation (n=332), exercise ECG (n=304), and signal averaged ECG (n=118) when performed. ER was associated with a trend toward late depolarization, in general was suppressed with exercise and was unaffected by ajmaline. Inferior and horizontal patterns were, however, more likely to persist during exercise. Augmentation of ER with ajmaline was rare. CONCLUSIONS: The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness. The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology. The differing response of ER subtypes to exercise and ajmaline provocation suggests underlying mechanisms of both abnormal repolarization and depolarization. PMID- 27255968 TI - Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques. AB - Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies. Hence, the present study aimed to develop a simple, versatile model based on Computational Fluid Dynamics (CFD) simulation. Current observations of CFD have shown the regions of modulated shear stress by the disturbed fluid flow. To execute and validate the model in real sense, cell morphology, cytoskeletal arrangement, cell death, reactive oxygen species (ROS) profile, nitric oxide production and disturbed flow markers under the above condition were assessed. Endothelium at disturbed flow region which had been exposed to low shear stress and swirling flow pattern showed morphological and expression similarities with the pathological disturbed flow environment reported previously. Altogether, the proposed model can serve as a platform to simulate the real time micro-environment of disturbed flow associated with eccentric plaque shapes and the possibilities of studying its downstream events. PMID- 27255969 TI - A theoretical assessment of microplastic transport in river catchments and their retention by soils and river sediments. AB - The presence of microplastics (MPs) in the environment is a problem of growing concern. While research has focused on MP occurrence and impacts in the marine environment, very little is known about their release on land, storage in soils and sediments and transport by run-off and rivers. This study describes a first theoretical assessment of these processes. A mathematical model of catchment hydrology, soil erosion and sediment budgets was upgraded to enable description of MP fate. The Thames River in the UK was used as a case study. A general lack of data on MP emissions to soils and rivers and the mass of MPs in agricultural soils, limits the present work to serve as a purely theoretical, nevertheless rigorous, assessment that can be used to guide future monitoring and impact evaluations. The fundamental assumption on which modelling is based is that the same physical controls on soil erosion and natural sediment transport (for which model calibration and validation are possible), also control MP transport and storage. Depending on sub-catchment soil characteristics and precipitation patterns, approximately 16-38% of the heavier-than-water MPs hypothetically added to soils (e.g. through routine applications of sewage sludge) are predicted to be stored locally. In the stream, MPs < 0.2 mm are generally not retained, regardless of their density. Larger MPs with densities marginally higher than water can instead be retained in the sediment. It is, however, anticipated that high flow periods can remobilize this pool. Sediments of river sections experiencing low stream power are likely hotspots for deposition of MPs. Exposure and impact assessments should prioritize these environments. PMID- 27255971 TI - Caffeoylquinic Acid Derivatives Protect SH-SY5Y Neuroblastoma Cells from Hydrogen Peroxide-Induced Injury Through Modulating Oxidative Status. AB - Oxidative stress has been confirmed as a contribution to the pathogenesis and pathophysiology of many neurological disorders such as Alzheimer's disease and Parkinson's disease. Caffeoylquinic acids (CQAs) are considered to have anti oxidative stress ability in a previous study, but the structure-activity relationships (SARs) of CQAs in neuroprotective effects are still unclear. In the present study, we primarily expound the SARs of CQAs in counteracting H2O2 induced injury in SH-SY5Y cells. We found that CQAs (1-10) represented the protection of SH-SY5Y cells against H2O2-induced injury in varying degrees and malonyl groups could obviously increase the anti-oxidative stress ability of CQAs. Intensive studies of 4,5-O-dicaffeoyl-1-O-(malic acid methyl ester)-quinic acid (MDCQA) indicated that the mechanisms could potentially involve activation of endogenous antioxidant enzymes and the regulation of the phosphorylation of MAPKs and AKT. In conclusion, MDCQA could serve as a neuroprotective agent with a potential to attenuate oxidative stress. PMID- 27255972 TI - EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma. AB - We conducted this research to explore the role of latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus (EBV) in modulating the DNA damage response (DDR) and its regulatory mechanisms in radioresistance. Our results revealed that LMP1 repressed the repair of DNA double strand breaks (DSBs) by inhibiting DNA-dependent protein kinase (DNA-PK) phosphorylation and activity. Moreover, LMP1 reduced the phosphorylation of AMP-activated protein kinase (AMPK) and changed its subcellular location after irradiation, which appeared to occur through a disruption of the physical interaction between AMPK and DNA-PK. The decrease in AMPK activity was associated with LMP1-mediated glycolysis and resistance to apoptosis induced by irradiation. The reactivation of AMPK significantly promoted radiosensitivity both in vivo and in vitro. The AMPKalpha (Thr172) reduction was associated with a poorer clinical outcome of radiation therapy in NPC patients. Our data revealed a new mechanism of LMP1-mediated radioresistance and provided a mechanistic rationale in support of the use of AMPK activators for facilitating NPC radiotherapy. PMID- 27255973 TI - Design of a CRISPR-Cas system to increase resistance of Bacillus subtilis to bacteriophage SPP1. AB - Clustered regularly interspaced short palindromic repeats (CRISPR) together with CRISPR-associated (cas) genes form an adaptive prokaryotic immune system which provides acquired resistance against viruses and plasmids. Bacillus subtilis presently is the best-characterized laboratory model for Gram-positive bacteria and also widely used for industrial production of enzymes, vitamins and antibiotics. In this study, we show that type II-A CRISPR-Cas system from Streptococcus thermophilus can be transferred into B. subtilis and provides heterologous protection against phage infection. We engineered a heterologous host by cloning S. thermophilus Cas9 and a spacer targeting bacteriophage SPP1 into the chromosome of B. subtilis, which does not harbor its own CRISPR-Cas systems. We found that the heterologous CRISPR-Cas system is functionally active in B. subtilis and provides resistance against bacteriophage SPP1 infection. The high efficiency of the acquired immunity against phage could be useful in generation of biotechnologically important B. subtilis strains with engineered chromosomes. PMID- 27255970 TI - The Regulation of GluN2A by Endogenous and Exogenous Regulators in the Central Nervous System. AB - The NMDA receptor is the most widely studied ionotropic glutamate receptor, and it is central to many physiological and pathophysiological processes in the central nervous system. GluN2A is one of the two main types of GluN2 NMDA receptor subunits in the forebrain. The proper activity of GluN2A is important to brain function, as the abnormal regulation of GluN2A may induce some neuropsychiatric disorders. This review will examine the regulation of GluN2A by endogenous and exogenous regulators in the central nervous system. PMID- 27255974 TI - Isolation and structure determination of a new lantibiotic cinnamycin B from Actinomadura atramentaria based on genome mining. AB - New lantibiotic cinnamycin B was isolated from the extract of Actinomadura atramentaria NBRC 14695(T), based on genome mining and chemical investigation. The partial structure of cinnamycin B was established by 2D NMR experiments, which indicated that cinnamycin B had same methyl lanthionine bridging pattern with cinnamycin. The reduction with NaBH4-NiCl2 afforded the reduced cinnamycin B, and MS/MS experiment indicated the presence of hydroxy asparatic acid in the molecule. Cinnamycin B showed an antibacterial activity against Streptomyces antibioticus with dosage of 5 MUg (0.5MUL, 10 mg/mL solution) at spot-on-lawn testing method. The gene cluster of cinnamycin B on the genome of A. atramentaria was identified and discussed in comparison with that of cinnamycin. PMID- 27255975 TI - Succinic acid production by Actinobacillus succinogenes from batch fermentation of mixed sugars. AB - Succinic acid production from the monosaccharides xylose, arabinose, glucose, mannose and galactose was studied using the bacterium Actinobacillus succinogenes. In Duran bottle cultures, containing 10 g/L of each of sugar, succinic acid was produced from all sugars except for galactose. The highest succinate yield, 0.56 g/g, was obtained with glucose, whereas the succinate yield was 0.42, 0.38 and 0.44 g/g for xylose, mannose and arabinose, respectively. The specific succinate productivity was 0.7 g/g h for glucose, but below 0.2 g/g h for the other sugars. Batch bioreactor fermentations were carried out using a sugar mixture of the five sugars giving a total concentration of 50 g/L, mimicking the distribution of sugars in spent sulfite liquor (SSL) from Eucalyptus which is rich in xylose. In this mixture, an almost complete conversion of all sugars (except galactose) was achieved resulting in a final succinate concentration of 21.8-26.8 g/L and a total yield of 0.59-0.68 g/g. There was evidence of co-consumption of glucose and xylose, whereas mannose was consumed after glucose. The main by-products were acetate 0.14-0.20 g/g and formate 0.08-0.13 g/g. NADH balance calculations suggested that NADH required for succinate production was not met solely from formate and acetate production, but other means of NADH production was necessary. Results from mixed sugar fermentations were verified using SSL as substrate resulting in a succinate yield of 0.60 g/g. In addition, it was found that CO2 sparging could replace carbonate supply in the form of MgCO3 without affecting the succinate yield. PMID- 27255976 TI - Thoracoscopic removal of an intrapulmonary foreign body in a child. AB - A 9-year-old boy presented to our institution 6 months after falling on a needle that pierced his left chest wall. He presented to us after multiple unsuccessful attempts to have this foreign body removed at other hospitals. A thoracoscopic removal was successfully undertaken aided by fluoroscopy. This report shows how the needle's position and location were precisely defined by fluoroscopy, despite the needle being invisible on thoracoscopy. PMID- 27255977 TI - Reduced heterotrophy in the stony coral Galaxea fascicularis after life-long exposure to elevated carbon dioxide. AB - Ocean acidification imposes many physiological, energetic, structural and ecological challenges to stony corals. While some corals may increase autotrophy under ocean acidification, another potential mechanism to alleviate some of the adverse effects on their physiology is to increase heterotrophy. We compared the feeding rates of Galaxea fascicularis colonies that have lived their entire lives under ocean acidification conditions at natural carbon dioxide (CO2) seeps with colonies living under present-day CO2 conditions. When provided with the same quantity and composition of zooplankton as food, corals acclimatized to high CO2 showed 2.8 to 4.8 times depressed rates of zooplankton feeding. Results were consistent over four experiments, from two expeditions and both in field and chamber measurements. Unless replenished by other sources, reduced zooplankton uptake in G. fascicularis acclimatized to ocean acidification is likely to entail a shortage of vital nutrients, potentially jeopardizing their health and survival in future oceans. PMID- 27255978 TI - Evidence based treatment for unstable slipped upper femoral epiphysis: Systematic review and exploratory patient level analysis. AB - The management of slipped upper femoral epiphysis is controversial and evolving as insight into the condition develops. Loder introduced the concept of slip stability and demonstrated a strong association between poor outcome and instability. Almost half of patients with unstable slip developed femoral head osteonecrosis. This has been influential in surgeons' choice of treatments. Some surgeons have adopted a minimal intervention approach such as pinning in situ or gentle reduction and pinning whereas others advocated an urgent open reduction and stabilisation of slip using various surgical techniques. In this review we analysed the influence of various interventions, timing of surgery and severity of the slip on the outcome of unstable slip. PMID- 27255979 TI - Extremely Delayed Multiple Brain Metastases from Renal Cell Carcinoma: Remission Achieved with Total Surgical Removal: Case Report and Literature Review. AB - BACKGROUND: Late brain metastasis from renal cell carcinoma (RCC), which is generally considered as metastasis occurring more than 10 years after nephrectomy, often occurs as a solitary lesion, and total resection is recommended to achieve remission. CASE DESCRIPTION: We describe a rare case of multiple late brain metastases from RCC in a 60-year-old man who presented with 3 brain metastases from RCC 22 years after nephrectomy. Total removal of the 3 lesions achieved remission without adjuvant therapy. CONCLUSIONS: Total removal of late brain metastasis from RCC, even occurring with multiple lesions, can achieve total remission under specific conditions. PMID- 27255980 TI - Progress in tear microdesiccate analysis by combining various transmitted-light microscope techniques. AB - BACKGROUND: Tear desiccation on a glass surface followed by transmitted-light microscopy has served as diagnostic test for dry eye. Four distinctive morphological domains (zones I, II, III and transition band) have been recently recognized in tear microdesiccates. Physicochemical dissimilarities among those domains hamper comprehensive microscopic examination of tear microdesiccates. Optimal observation conditions of entire tear microdesiccates are now investigated. One-MUl aliquots of tear collected from individual healthy eyes were dried at ambient conditions on microscope slides. Tear microdesiccates were examined by combining low-magnification objective lenses with transmitted-light microscopy (brightfield, phase contrasts Ph1,2,3 and darkfield). RESULTS: Fern like structures (zones II and III) were visible with all illumination methods excepting brightfield. Zone I was the microdesiccate domain displaying the most noticeable illumination-dependent variations, namely transparent band delimited by an outer rim (Ph1, Ph2), homogeneous compactly built structure (brightfield) or invisible domain (darkfield, Ph3). Intermediate positions of the condenser (BF/Ph1, Ph1/Ph2) showed a structured roughly cylindrical zone I. The transition band also varied from invisibility (brightfield) to a well-defined domain comprising interwoven filamentous elements (phase contrasts, darkfield). CONCLUSIONS: Imaging of entire tear microdesiccates by transmitted-light microscopy depends upon illumination. A more comprehensive description of tear microdesiccates can be achieved by combining illumination methods. PMID- 27255981 TI - Driving and Other Important Activities in Older Adulthood. PMID- 27255982 TI - Pitfalls and major issues in the histologic diagnosis of peripheral T-cell lymphomas: results of the central review of 573 cases from the T-Cell Project, an international, cooperative study. AB - Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of neoplasms that are derived from post-thymic lymphoid cells at different stages of differentiation with different morphological patterns, phenotypes and clinical presentations. PTCLs are highly diverse, reflecting the diverse cells from which they can originate and are currently sub-classified using World Health Organization (WHO) 2008 criteria. In 2006 the International T-Cell Lymphoma Project launched the T-Cell Project, building on the retrospective study previously carried on by the network, with the aim to prospectively collect accurate data to improve knowledge on this group of lymphomas. Based on previously published reports from International Study Groups it emerged that rendering a correct classification of PTCLs is quite difficult because the relatively low prevalence of these diseases results in a lack of confidence by most pathologists. This is the reason why the T-Cell Project requested the availability of diagnostic material from the initial biopsy of each patient registered in the study in order to have the initial diagnosis centrally reviewed by expert hematopathologists. In the present report the results of the review process performed on 573 cases are presented. Overall, an incorrect diagnosis was centrally recorded in 13.1% cases, including 8.5% cases centrally reclassified with a subtype eligible for the project and 4.6% cases misclassified and found to be disorders other than T-cell lymphomas; 2.1% cases were centrally classified as T-Cell disorders not included in the study population. Thus, the T-Cell Project confirmed the difficulties in providing an accurate classification when a diagnosis of PTCLs is suspected, singled out the major pitfalls that can bias a correct histologic categorization and confirmed that a centralized expert review with the application of adequate diagnostic algorithms is mandatory when dealing with these tumours. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27255983 TI - Effect of Biofilm on Passive Sampling of Dissolved Orthophosphate Using the Diffusive Gradients in Thin Films Technique. AB - We evaluated the possibility of sampling dissolved orthophosphate using the diffusive gradient in thin films (DGT) technique with a phosphate ion-imprinted polymer (PIP)-based adsorbent and assessed the effect of biofilm on the DGT measurement. The composition of biofilm formed on the DGT surface was analyzed, and the effect of biofouling on the diffusion coefficient of the analyte was investigated. The corrected diffusion coefficient for the biofouled DGT was estimated and used for the calculation of the DGT equation. PIP-binding gels had a higher adsorption affinity for orthophosphate than for the other anions, indicating its selectivity for orthophosphate. The concentrations predicted via DGT agreed well with the concentrations determined in the bulk solutions. Sampling of orthophosphate using PIP-DGT was consistent over a pH range of 3-9 and ionic strength range of 0.01-10 000 MUM. Other P compounds cannot be measured using the PIP-DGT technique. The diffusion coefficient of the orthophosphate linearly decreased with increasing thickness of the biofilm. This sampling method performed predictably in freshwater when the biofilm was not formed or when value for the biofilm interference was reduced by using the corrected diffusion coefficient. PMID- 27255984 TI - Effect of subthreshold slope on the sensitivity of nanoribbon sensors. AB - In this work, we investigate how the sensitivity of a nanowire or nanoribbon sensor is influenced by the subthreshold slope of the sensing transistor. Polysilicon nanoribbon sensors are fabricated with a wide range of subthreshold slopes and the sensitivity is characterized using pH measurements. It is shown that there is a strong relationship between the sensitivity and the device subthreshold slope. The sensitivity is characterized using the current sensitivity per pH, which is shown to increase from 1.2% ph(-1) to 33.6% ph(-1) as the subthreshold slope improves from 6.2 V dec(-1) to 0.23 V dec(-1) respectively. We propose a model that relates current sensitivity per pH to the subthreshold slope of the sensing transistor. The model shows that sensitivity is determined only on the subthreshold slope of the sensing transistor and the choice of gate insulator. The model fully explains the values of current sensitivity per pH for the broad range of subthreshold slopes obtained in our fabricated nanoribbon devices. It is also able to explain values of sensitivity reported in the literature, which range from 2.5% pH(-1) to 650% pH(-1) for a variety of nanoribbon and nanowire sensors. Furthermore, it shows that aggressive device scaling is not the key to high sensitivity. For the first time, a figure of-merit is proposed to compare the performance of nanoscale field effect transistor sensors fabricated using different materials and technologies. PMID- 27255985 TI - Is it necessary to use ABR in myringosclerosis studies? PMID- 27255986 TI - Iris metastasis. PMID- 27255987 TI - [Macroglossia in Madelung's disease]. PMID- 27255988 TI - Septic sacroilitis and psoas abscess. PMID- 27255989 TI - Age-related distance esotropia: Clinical features and therapeutic outcomes. AB - OBJECTIVE: To describe the clinical characteristics and surgical outcomes of a group of patients with age-related distance esotropia (ARDE). METHODS: A retrospective study was conducted on a consecutive case series of 16 adult patients diagnosed with ARDE between 2008 and 2015. The clinical features evaluated included mean age and gender, primary position deviations at distance and near, measured in prism dioptres (pd), treatment offered in each case, and post-surgical deviations. Ductions and versions were full, with no evidence of lateral rectus paresis. None of these patients had any obvious underlying neurological disorder, such as, high myopia or thyroid disease. A good result is considered to be the disappearance of diplopia in all positions of gaze. RESULTS: A total of 16 patients (11 females [68.8%]) were identified. The mean age at diagnosis was 78.19+/-6.77 years. The mean initial esodeviation was 2.25+/-3.08 pd at near (-4 to +8 pd) and 9.5+/-4.18 pd at distance (2 to 18 pd). Treatment was not necessary in 5 cases because the symptoms were intermittent or well tolerated. Of the 11 patients with symptoms, one was corrected with an external base therapeutic prism. Botulinum toxin was administered in another patient, without satisfactory results. Unilateral medial rectus muscle recession was performed on one patient, and unilateral lateral rectus plication on 7 patients, indicating prisms before surgery. One patient refused surgery despite continuous diplopia in far vision. After a mean follow-up of 16.5 months, all operated patients were asymptomatic. CONCLUSIONS: Not all patients with ARDE require treatment, as the tolerance to diplopia varies from one subject to another. Both medial rectus weakening and lateral rectus strengthening provides excellent results. PMID- 27255990 TI - Antonio Vena was the first. PMID- 27255991 TI - T cells expressing CD19-specific Engager Molecules for the Immunotherapy of CD19 positive Malignancies. AB - T cells expressing chimeric antigen receptors (CARs) or the infusion of bispecific T-cell engagers (BITEs) have shown antitumor activity in humans for CD19-positive malignancies. While BITEs redirect the large reservoir of resident T cells to tumors, CAR T cells rely on significant in vivo expansion to exert antitumor activity. We have shown that it is feasible to modify T cells to secrete solid tumor antigen-specific BITEs, enabling T cells to redirect resident T cells to tumor cells. To adapt this approach to CD19-positive malignancies we now generated T cells expressing secretable, CD19-specific BITEs (CD19-ENG T cells). CD19-ENG T cells recognized tumor cells in an antigen-dependent manner as judged by cytokine production and tumor killing, and redirected bystander T cells to tumor cells. Infusion of CD19-ENG T cells resulted in regression of leukemia or lymphoma in xenograft models and a survival advantage in comparison to control mice. Genetically modified T cells expressing engager molecules may present a promising addition to current CD19-targeted immunotherapies. PMID- 27255992 TI - In vivo dynamics of GFRalpha1-positive spermatogonia stimulated by GDNF signals using a bead transplantation assay. AB - In mouse testes, spermatogonial stem cells (SSCs), a subpopulation of GFRalpha1 (GDNF family receptor-alpha1)-positive spermatogonia, are widely distributed along the convoluted seminiferous tubules. The proliferation and differentiation of the SSCs are regulated in part by local expression of GDNF (glial cell-derived neurotorphic factor), one of major niche factors for SSCs. However, the in vivo dynamics of the GDNF-stimulated GFRalpha1-positive spermatogonia remains unclear. Here, we developed a simple method for transplanting DiI-labeled and GDNF-soaked beads into the mouse testicular interstitium. By using this method, we examined the dynamics of GFRalpha1-positive spermatogonia in the tubular walls close to the transplanted GDNF-soaked beads. The bead-derived GDNF signals were able to induce the stratified aggregate formation of GFRalpha1-positive undifferentiated spermatogonia by day 3 post-transplantation. Each aggregate consisted of tightly compacted Asingle and marginal Apaired-Aaligned GFRalpha1-positive spermatogonia and was surrounded by Aaligned GFRalpha1-negative spermatogonia at more advanced stages. These data not only provide in vivo evidence for the inductive roles of GDNF in forming a rapid aggregation of GFRalpha1-positive spermatogonia but also indicate the usefulness of this in vivo assay system of various growth factors for the stem/progenitor spermatogonia in mammalian spermatogenesis. PMID- 27255993 TI - Identification and bioactivity evaluation of two novel temporins from the skin secretion of the European edible frog, Pelophylax kl. esculentus. AB - The amphibian temporins, amongst the smallest antimicrobial peptides (AMPs), are alpha-helical, amphipathic, hydrophobic and cationic and are active mainly against Gram-positive bacteria but inactive or weakly active against Gram negative bacteria. Here, we report two novel members of the temporin family, named temporin-1Ee (FLPVIAGVLSKLFamide) and temporin-1Re (FLPGLLAGLLamide), whose biosynthetic precursor structures were deduced from clones obtained from skin secretion-derived cDNA libraries of the European edible frog, Pelophylax kl. esculentus, by 'shotgun' cloning. Deduction of the molecular masses of each mature processed peptide from respective cloned cDNAs was used to locate respective molecules in reverse-phase HPLC fractions of secretion. Temporin-1Ee (MIC = 10 MUM) and temporin-1Re (MIC = 60 MUM) were both found to be active against Gram-positive Staphylococcus aureus, but retaining a weak haemolytic activity. To our knowledge, Single-site substitutions can dramatically change the spectrum of activity of a given temporin. Compared with temporine-1Ec, just one chemically-conservative substitution (Val8 instead of Leu8), temporin-1Ee bearing a net charge of +2 displays broad-spectrum activity with particularly high potency on the clinically relevant Gram-negative strains, Escherichia coli (MIC = 40 MUM). These factors bode well for translating temporins to be potential drug candidates for the design of new and valuable anti-infective agents. PMID- 27255994 TI - Elevated expression of CD93 promotes angiogenesis and tumor growth in nasopharyngeal carcinoma. AB - CD93, also known as the complement component C1q receptor (C1qRp), has been reported to promote the progression of some cancer types. However, the expression and physiological significance of CD93 in nasopharyngeal carcinoma (NPC) remain largely elusive. In this study, we first examined the expression of CD93 in NPC and experimentally manipulated its expression. We observed that vascular CD93 expression is elevated in NPC and is correlated with T classification, N classification, distant metastasis, clinical stage and poor prognosis (all P < 0.05). In addition, overexpression of CD93 promoted angiogenesis in vitro. What's more, we found that CD93 was highly expressed in NPC tissues and cells, and the regulation of CD93 on cell proliferation was determined by cell counting kit (CCK)-8 assay and cell cycle analyses. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as CD93 to improve NPC treatment. PMID- 27255995 TI - Effects of light-emitting diode spectra on the vertebrate ancient long opsin and gonadotropin hormone in the goldfish Carassius auratus. AB - We determined the molecular mechanism underlying the environmental (photoperiodic) regulation of sexual maturation in fish, we examined the expression of sexual maturation-related hormones and vertebrate ancient long opsin (VAL-opsin) in goldfish (Carassius auratus) exposed to different light spectra (red and green light-emitting diodes). We further evaluated the effect of exogenous gonadotropin hormone (GTH) on the expression of VAL-opsin under different light conditions. Our results demonstrated that the expression of GTHs was higher in the fish exposed to green light, and VAL-opsin levels were increased in the fish receiving GTH injection. Therefore, we have uncovered a molecular mechanism underlying the environmental (light)-induced trigger for sexual maturation: VAL-opsin is activated by green light and GTH, which promotes the expression of sexual maturation genes. PMID- 27255996 TI - Network-based analysis for identification of candidate genes for colorectal cancer progression. AB - Although high-throughput biological technologies have been producing a vast amount of multi-omics data regarding cancer genomics and several disease susceptible genes have been reported, many of these genes are likely to be irrelevant for the cancer process because only one feature of the tumor pathway could be focused on. By identifying 'CpG core', which was extracted from CpG sites in genomic DNA by our newly developed method, we performed integrated analysis using gene expression and DNA methylation profiles of 116 colorectal cancer samples. First, based on gene expression values, colorectal cancer samples were divided into three clusters (Cluster-1, -2, and -3) by k-means clustering. The 5-year overall survival rates of colorectal cancer patients were 74.8%, 29.2%, and 29.4% in Cluster-1, -2, and -3, respectively, and the prognosis of Cluster-2 was significantly poorer than that of the other two clusters owing to liver metastasis (P < 0.001). Second, each cluster was divided into two subgroups based on methylation status, and the 5-year overall survival rate of Cluster-1H (36.8%) was significantly shorter than that of Cluster-1L (96.1%) due to the accumulation of aberrant DNA methylation (P = 0.014). Third, network-based analysis using expression and methylation profiles demonstrated that nucleoporin family genes were downregulated in Cluster-2 and that the PTX3 gene was highly methylated in Cluster-1H. These combined data indicate that integrated analysis can identify disease characteristics that would be missed using single comprehensive analysis, and that multiple pathways would play pivotal roles in the liver metastasis of colorectal cancer. PMID- 27255997 TI - MUS81 is associated with cell proliferation and cisplatin sensitivity in serous ovarian cancer. AB - The dysfunction of DNA damage repair (DDR) pathway contributes to tumorigenesis and drug-resistance in cancer. MUS81 is a member of the conserved xeroderma pigmentosum group F (XPF) family protein of endonucleases, which is important to the DDR pathway. However, the role of MUS81 in the development of ovarian cancer remains uncertain. To explore the expression of MUS81 and its association to serous ovarian cancer (SOC), 43 biopsies of SOC patients were detected by qRT PCR, and 29 specimens were further performed by immunohistochemistry analysis. Here, we observed that MUS81 was over-expressed in SOC tissues at both transcript and protein levels, and the expression level of MUS81 protein in ovarian cancer cell lines was also higher than that in human normal ovarian surface epithelial cell line (HOSEpiC). We also found that down-regulation of MUS81 expression in ovarian cancer cells inhibited cell proliferation and colony formation ability, and influenced cell cycle progression. Moreover, inhibition of MUS81 expression induced cellular senescence and enhanced the antitumor effect of cisplatin. Down regulation of MUS81 expression could suppress the growth and development of SOC. These results indicate that MUS81 might play important roles in the progression of SOC and influence the antitumor effect of cisplatin. PMID- 27255998 TI - The regulatory domain of human tryptophan hydroxylase 1 forms a stable dimer. AB - The three eukaryotic aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase have essentially identical catalytic domains and discrete regulatory domains. The regulatory domains of phenylalanine hydroxylase form ACT domain dimers when phenylalanine is bound to an allosteric site. In contrast the regulatory domains of tyrosine hydroxylase form a stable ACT dimer that does not bind the amino acid substrate. The regulatory domain of isoform 1 of human tryptophan hydroxylase was expressed and purified; mutagenesis of Cys64 was required to prevent formation of disulfide linked dimers. The resulting protein behaved as a dimer upon gel filtration and in analytical ultracentrifugation. The sw value of the protein was unchanged from 2.7 to 35 MUM, a concentration range over which the regulatory domain of phenylalanine hydroxylase forms both monomers and dimers, consistent with the regulatory domain of tryptophan hydroxylase 1 forming a stable dimer stable that does not undergo a monomer-dimer equilibrium. Addition of phenylalanine, a good substrate for the enzyme, had no effect on the sw value, consistent with there being no allosteric site for the amino acid substrate. PMID- 27255999 TI - Taking It at "Face Value": The Use of Face Processing Strategies in Bipolar Disorder and Schizophrenia. AB - OBJECTIVES: Use of appropriate face processing strategies is important for facial emotion recognition, which is known to be impaired in schizophrenia (SZ) and bipolar disorder (BD). There is preliminary evidence of abnormalities in the use of face processing strategies in the former, but there has been no explicit attempt to assess face processing in patients with BD. METHODS: Twenty-eight BD I, 28 SZ, and 28 healthy control participants completed tasks assessing featural and configural face processing. The facial inversion effect was used as a proxy of second order configural face processing and compared to featural face processing performance (which is known to be relatively less affected by facial inversion). RESULTS: Controls demonstrated the usual second-order inversion pattern. In the BD group, the absence of a second-order configural inversion effect in the presence of a disproportionate bias toward a featural inversion effect was evident. Despite reduced accuracy performance in the SZ group compared to controls, this group unexpectedly showed a normal second-order configural accuracy inversion pattern. This was in the context of a reverse inversion effect for response latency, suggesting a speed-versus-accuracy trade-off. CONCLUSIONS: To our knowledge, this is the first study to explicitly examine and contrast face processing in BD and SZ. Our findings indicate a generalized impairment on face processing tasks in SZ, and the presence of a second-order configural face processing impairment in BD. It is possible that these face processing impairments represent a catalyst for the facial emotion recognition deficits that are commonly reported in the literature. (JINS, 2016, 22, 652-661). PMID- 27256001 TI - Introduction to this issue: Conditional Release: Part II. PMID- 27256000 TI - Capecitabine plus paclitaxel induction treatment in gastric cancer patients with liver metastasis: a prospective, uncontrolled, open-label Phase II clinical study. AB - AIM: To determine the overall survival rate, radical resection rate, objective response rate and safety of capecitabine plus paclitaxel induction chemotherapy in gastric cancer patients with liver metastases. PATIENTS & METHODS: A total of 30 patients (median age: 59.5 years) diagnosed as gastric adenocarcinoma with liver metastasis received >=3 cycles of capecitabine and paclitaxel therapy followed by radical resection 4-6 weeks after termination of chemotherapy. RESULTS: The median survival time was 11.4 months, and the objective response rate was 53.3%. The radical resection rate was 23.3% (95% CI: 9.9-42.3). Major toxicities included grade 3 neutropenia (10.0%) and grade 3 diarrhea (3.3%). CONCLUSION: Capecitabine plus paclitaxel chemotherapy may be effective and safe to improve overall survival and the resection rate of gastric cancer patients with liver metastases. ClinicalTrials.gov identifier: NCT0116704. PMID- 27256002 TI - Conditional Release of Forensic Psychiatric Patients Consistent with or Contrary to Behavioral Experts' Recommendations in the Netherlands: Prevalence Rates, Patient Characteristics and Recidivism After Discharge from Conditional Release. AB - The present study examined a group of 447 Dutch forensic psychiatric patients on conditional release (CR). After a brief overview of the Dutch CR system for forensic psychiatric patients is presented, two sets of factors were studied: factors associated with behavioral experts' recommendations on CR readiness (prevalence rates of recommendations in contrast to or consistent with the judge's decision on CR, written vs. oral recommendations and consensus among parties); and characteristics of forensic psychiatric patients on CR imposed consistent with or contrary to behavioral experts' recommendations (i.e., demographic variables, psychopathology, judicial background and outcomes of violent behavior). Patients on CR consistent with or contrary to the behavioral experts' recommendations did not differ in demographic background variables and psychopathology. Patients on CR contrary to the behavioral experts' recommendations, however, had more prior convictions, and their index offense more often included a sex offense and a property offense (with or without violence) as compared to patients on CR consistent with the behavioral experts' recommendations. In addition, decisions contrary to the behavioral experts' recommendations were more often reached after a 3-month continuation adjournment and after an appeal. Also, patients on CR contrary to the behavioral experts' recommendations were less often found to have been on trial leave before their CR. Finally, recidivism rates were found to be much higher for those on CR contrary to, as compared with those on CR consistent with the behavioral experts' recommendations. However, when corrected for other well-known static predictors of recidivism, this significant difference was no longer prevalent. The implications for evaluators' CR readiness reports and lessons that may be learned from the Dutch forensic psychiatric CR system are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27256003 TI - Closing Italian Forensic Psychiatry Hospitals in Favor of Treating Insanity Acquittees in the Community. AB - Originally a hedge against the death penalty, the insanity defense came to offer hospitalization as an alternative to imprisonment. In the late 19th century Italy opened inpatient services first for mentally ill prisoners and then for offenders found not guilty by reason of insanity. Within the past decade, a series of decrees has resulted in transferring the responsibility for treating NGRI acquittees and "dangerous" mentally ill prisoners from the Department of Justice to the Department of Health, and their treatment from Italy's high security forensic psychiatric hospitals (OPGs) to community regional facilities (REMSs, Residences for the Execution of Security Measures), community mental health facilities, one of which is located in each region of Italy. Today community REMSs provide the treatment and management of socially dangerous offenders. The dynamic evolution of Italy's progressive mental health system for insanity acquittees, to our knowledge the most libertarian, community oriented approach of any country, is retraced. Discussion includes cautionary concerns as well as potential opportunities for improvements in mental health services. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27256004 TI - Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer. AB - PURPOSE: Immune checkpoint molecules are key targets for the treatment of various malignancies. Due to the heterogeneity of advanced gastric cancer (GC), the role of programmed cell death ligand 1 (PD-L1) expression as a tumor biomarker remains controversial. In this study, the prognostic value of soluble PD-L1 (sPD-L1) levels in serum samples was assessed in patients with metastatic GC. METHODS: All patients received first-line treatment with fluoropyrimidine and platinum chemotherapy, and trastuzumab was added for HER2-positive patients. Serum levels of sPD-L1 were measured by enzyme-linked immunosorbent assay. RESULTS: Among 75 metastatic GC patients, the median serum sPD-L1 level was 0.704 ng/ml (range <0.156-3.214). Serum sPD-L1 was significantly higher in patients with a high versus a low white blood cell count at baseline. When the cutoff value was set as the median, multivariate analyses showed that high sPD-L1 levels were associated with worse overall survival compared with low sPD-L1 levels (HR 2.218, 95 % CI 1.139-4.320, P = 0.019). Regardless of HER2 status, overall survival tended to be shorter in patients with high sPD-L1 compared with low sPD-L1. There was no significant association between sPD-L1 level and progression-free survival on the first-line treatment of metastatic GC. CONCLUSIONS: High serum levels of sPD-L1 correlated with worse overall survival on the first-line chemotherapy in metastatic GC patients. PMID- 27256005 TI - Abundance of sulfur-degrading bacteria in a benthic bacterial community of shallow sea sediment in the off-Terengganu coast of the South China Sea. AB - This study for the first time provides insight into the bacterial community in the benthic region of the Off-Terengganu Coastline, which is considered to be anthropogenically polluted due to heavy fishing vessel commotion. Subsurface bacteria were randomly collected from two locations at different depths and were examined using the 16S rDNA V3-V4 marker gene on the IlluminaTM Miseq platform. In addition, the physiochemical parameters of the sediment were also measured. Surprisingly, the results show a high diversity of sulfur-oxidizing bacteria in the surveyed area, where Sulfurovum sp. was identified to predominate the overall bacterial community. The physiochemical parameters reveal insufficient evidence of hydrothermal vents in the surveyed area. However, there are traces of hydrocarbon pollutants such as gasoline, diesel, and mineral oil in this area. It is assumed that sediment accumulation in the lee of breakwater plays an important role in trapping the runoff from the nearby harbor, which includes oil spills. Based on the common knowledge, Sulvurofum sp. is a native bacterium that exists in deep hydrothermal vents and volcanic territories. Although the reason for the abundance of Sulfurovum sp. in the surveyed area is still unclear, there is a possibility that metabolic adaptation plays an important role in regulating hydrocarbon pollutants for survival. The work presented in this paper therefore has profound implications for future studies on Sulfurovum sp. versatility. However, future research is needed to strengthen the findings of this study and to provide a better evidence regarding the metabolic response of this bacterium toward hydrocarbon pollutants. PMID- 27256006 TI - Tumorigenesis: Cancer goes tick tock. PMID- 27256008 TI - Epigenetics: Misdirecting methylation to drive oncogenesis. PMID- 27256010 TI - Palatal injection for removal of maxillary teeth: is it required? A systematic review. AB - There is a growing body of work examining whether a palatal injection is necessary for the extraction of maxillary teeth with contemporary local anaesthetics. The available literature was reviewed systematically by conducting a search of the PubMed, EMBASE, and Cochrane CENTRAL databases for trials examining outcomes of maxillary tooth extraction where buccal injection of local anaesthetic only was used for one or more test groups. The selected studies were reviewed for study type, sample size, quality, participant characteristics and methodology, outcome variables, and findings. Fifteen studies met the inclusion criteria. Six of the studies were randomized controlled trials. Four studies were controlled clinical trials that did not report randomization. Five were clinical trials that were not controlled and examined outcomes of one or more test groups. The pain of local anaesthetic injection(s) in the test group (buccal injection only) versus control group (buccal and palatal injection), number of cases requiring supplemental buccal or palatal injection in cases of unsuccessful local anaesthesia, and pain during the procedure were designated as primary outcomes. Pain on probing of the mucosa was designated as a secondary outcome. All nine controlled studies that assessed pain during the procedure found no statistically significant difference between the test and control groups. PMID- 27256009 TI - Real-time automated clinical deterioration alerts predict thirty-day hospital readmission. AB - INTRODUCTION: Clinical deterioration alerts (CDAs) are increasingly employed to identify deteriorating patients. METHODS: We performed a retrospective study to determine whether CDAs predict 30-day readmission. Patients admitted to 8 general medicine units were assessed for all-cause 30-day readmission. RESULTS: Among 3015 patients, 567 (18.8%) were readmitted within 30 days. Patients triggering a CDA (n = 1141; 34.4%) were more likely to have a 30-day readmission (23.6% vs 15.9%; P < 0.001). Logistic regression identified triggering of a CDA to be independently associated with 30-day readmission (odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.26-1.55; P = 0.001). Other predictors were: an emergency department visit in the previous 6 months (OR: 1.23; 95% CI:, 1.20 1.26; P < 0.001), increasing age (OR: 1.01; 95% CI: 1.01-1.02; P = 0.003), presence of connective tissue disease (OR: 1.63; 95% CI: 1.34-1.98; P = 0.012), diabetes mellitus with end-organ complications (OR: 1.23; 95% CI: 1.13-1.33; P = 0.010), chronic renal disease (OR: 1.16; 95% CI: 1.08-1.24; P = 0.034), cirrhosis (OR: 1.25; 95% CI: 1.17-1.33; P < 0.001), and metastatic cancer (OR: 1.12; 95% CI: 1.08-1.17; P = 0.002). Addition of the CDA to the other predictors added only modest incremental value for the prediction of hospital readmission. CONCLUSIONS: Readily identifiable clinical variables can be identified that predict 30-day readmission. It may be important to include these variables in existing prediction tools if pay for performance and across-institution comparisons are to be "fair" to institutions that care for more seriously ill patients. Journal of Hospital Medicine 2016;11:768-772. (c) 2016 Society of Hospital Medicine. PMID- 27256011 TI - Graftless sinus augmentation with simultaneous dental implant placement: clinical results and biological perspectives. AB - After a sinus lifting procedure, the compartment around the implants under the sinus mucosal lining in the sinus floor is filled with a blood clot from surrounding bleeding. The aim of this study was to evaluate the feasibility of bone formation following graftless sinus lifting with the simultaneous placement of dental implants. Thirty graftless sinus lifting procedures were performed and 72 dental implants placed in 18 consecutive patients, using the lateral window approach. Clinical and radiological follow-up was conducted throughout the 6 month healing period. Biopsies of 30 cases were collected at 6 months post treatment: 15 biopsies were taken from the newly formed bone near the basal floor and 15 from the newly formed bone near the elevated membrane. New bone consolidation in the maxillary sinus was apparent radiologically and histologically at 6 months after sinus augmentation, providing an average 6.14+/ 1.34mm of bone-gain. Based on histological analysis and histomorphometric data, the consolidated bone in the augmented sinus comprised 56.7+/-11.9% to 59.9+/ 13.4% vital bone tissue. Out of the 72 implants placed, only four failed, indicating a 94% overall implant survival rate. Based on this case series, blood clot can be considered autologous osteogenic graft material, to which osteoprogenitors can migrate, differentiate, and regenerate bone. PMID- 27256012 TI - Modified tragus edge approach for mid-level or low condylar fractures. AB - The aim of this study was to evaluate and report a modified tragus edge approach (MTEA) for surgical access to mid-level or low condylar fractures. The MTEA was used on 45 patients (59 sides). All of the patients were reviewed for scarring, parotid fistula, facial nerve function, occlusion, deviation, and limitation of mouth opening (MO). Forty-one patients (64 sides) with middle or low level condylar fractures who underwent surgery by retromandibular approach during the same period were selected for comparison. In the MTEA group, scars were not obvious and there was no parotid fistula. The occlusion of four cases (8.9%) was not ideal, but returned to normal after 2 weeks of intermaxillary traction. Temporary facial nerve damage was present on two sides (3.4%). MO was not deviated in any patient, but was limited in the first 2 weeks after operation in three cases (6.7%). The risks of facial nerve dysfunction and parotid fistula were much higher in the retromandibular approach group than in the MTEA group, while the risks of malocclusion and limitation of MO were similar. MTEA is safe and has good aesthetic outcomes. MTEA represents an appropriate surgical access to mid-level and low condylar fractures. PMID- 27256007 TI - The isomerase PIN1 controls numerous cancer-driving pathways and is a unique drug target. AB - Targeted drugs have changed cancer treatment but are often ineffective in the long term against solid tumours, largely because of the activation of heterogeneous oncogenic pathways. A central common signalling mechanism in many of these pathways is proline-directed phosphorylation, which is regulated by many kinases and phosphatases. The structure and function of these phosphorylated proteins are further controlled by a single proline isomerase: PIN1. PIN1 is overactivated in cancers and it promotes cancer and cancer stem cells by disrupting the balance of oncogenes and tumour suppressors. This Review discusses the roles of PIN1 in cancer and the potential of PIN1 inhibitors to restore this balance. PMID- 27256013 TI - Objective Non-irradiant Imaging of Fat Distribution: New Essential Tools for the Bariatric Surgery? PMID- 27256014 TI - Factors Leading to Self-Removal from the Bariatric Surgery Program After Attending the Orientation Session. AB - BACKGROUND: Bariatric surgery orientation sessions are often the first point of contact and a recommended component of pre-bariatric surgery assessment. Self removal rates after bariatric program orientation are as high as 25 % despite the proven efficacy of this procedure. The objective of this study was to identify factors contributing to patient self-removal after orientation using a mixed method approach. METHODS: Patients who attended the Toronto Western Hospital Bariatric Surgery Program orientation between 2012 and 2013 and then self-removed from the program (N = 216) were included in the study. Subjects were interviewed via telephone using a semi-structured interview guide, generating both quantitative and qualitative data. Factors leading to discontinuation were rated on a five-point Likert scale. Qualitative data was analyzed using constant comparative methodology. RESULTS: The response rate was 59 % with a 40.7 % completion rate (N = 88). Concerns about potential surgical risks and complications and the ability to adapt to changes in eating and drinking post operatively were identified as the top two factors for patients' self-removal from the program. Thematic analysis uncovered 11 major themes related to patient self-removal. Unexpected themes include perceived personal suitability for the surgery, family impact of surgery, miscommunication with the family physician, and fears related to the orientation information. CONCLUSIONS: This is one of the first studies examining barriers to bariatric surgery in the pre-operative setting and offers new insights into the reasons patients self-remove from bariatric surgery programs. This study may inform bariatric orientation program changes resulting in improved access to this effective surgical intervention. PMID- 27256015 TI - The ABA receptor PYL9 together with PYL8 plays an important role in regulating lateral root growth. AB - Abscisic acid is a phytohormone regulating plant growth, development and stress responses. PYR1/PYL/RCAR proteins are ABA receptors that function by inhibiting PP2Cs to activate SnRK2s, resulting in phosphorylation of ABFs and other effectors of ABA response pathways. Exogenous ABA induces growth quiescence of lateral roots, which is prolonged by knockout of the ABA receptor PYL8. Among the 14 members of PYR1/PYL/RCAR protein family, PYL9 is a close relative of PYL8. Here we show that knockout of both PYL9 and PYL8 resulted in a longer ABA-induced quiescence on lateral root growth and a reduced sensitivity to ABA on primary root growth and lateral root formation compared to knockout of PYL8 alone. Induced overexpression of PYL9 promoted the lateral root elongation in the presence of ABA. The prolonged quiescent phase of the pyl8-1pyl9 double mutant was reversed by exogenous IAA. PYL9 may regulate auxin-responsive genes in vivo through direct interaction with MYB77 and MYB44. Thus, PYL9 and PYL8 are both responsible for recovery of lateral root from ABA inhibition via MYB transcription factors. PMID- 27256017 TI - Porcine respiratory disease complex: Interaction of vaccination and porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, and Mycoplasma hyopneumoniae. AB - Porcine respiratory disease is a multifactorial and complex disease caused by a combination of infectious pathogens, environmental stressors, differences in production systems, and various management practices; hence the name porcine respiratory disease complex (PRDC) is used. Porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and Mycoplasma hyopneumoniae are considered to be the most important pathogens that cause PRDC. Although interactions among the three major respiratory pathogens are well documented, it is also necessary to understand the interaction between vaccines and the three major respiratory pathogens. PRRSV and M. hyopneumoniae are well known to potentiate PCV2-associated lesions; however, PRRSV and mycoplasmal vaccines can both enhance PCV2 viraemia regardless of the effects of the actual PRRSV or M. hyopneumoniae infection. On the other hand, M. hyopneumoniae potentiates the severity of pneumonia induced by PRRSV, and vaccination against M. hyopneumoniae alone is also able to decrease PRRSV viraemia and PRRSV-induced lung lesions in dually infected pigs. This review focuses on (1) interactions between PCV2, PRRSV, and M. hyopneumoniae; and (2) interactions between vaccines and the three major respiratory pathogens. PMID- 27256016 TI - Cost-effectiveness of zoledronic acid and strontium-89 as bone protecting treatments in addition to chemotherapy in patients with metastatic castrate refractory prostate cancer: results from the TRAPEZE trial (ISRCTN 12808747). AB - OBJECTIVE: To evaluate the cost-effectiveness of adding zoledronic acid or strontium-89 to standard docetaxel chemotherapy for patients with castrate refractory prostate cancer (CRPC). PATIENTS AND METHODS: Data on resource use and quality of life for 707 patients collected prospectively in the TRAPEZE 2 * 2 factorial randomised trial (ISRCTN 12808747) were used to assess the cost effectiveness of i) zoledronic acid versus no zoledronic acid (ZA vs. no ZA), and ii) strontium-89 versus no strontium-89 (Sr89 vs. no Sr89). Costs were estimated from the perspective of the National Health Service in the UK and included expenditures for trial treatments, concomitant medications, and use of related hospital and primary care services. Quality-adjusted life-years (QALYs) were calculated according to patients' responses to the generic EuroQol EQ-5D-3L instrument, which evaluates health status. Results are expressed as incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves. RESULTS: The per-patient cost for ZA was L12 667, L251 higher than the equivalent cost in the no ZA group. Patients in the ZA group had on average 0.03 QALYs more than their counterparts in no ZA group. The ICER for this comparison was L8 005. Sr89 was associated with a cost of L13 230, L1365 higher than no Sr89, and a gain of 0.08 QALYs compared to no Sr89. The ICER for Sr89 was L16 884. The probabilities of ZA and Sr89 being cost-effective were 0.64 and 0.60, respectively. CONCLUSIONS: The addition of bone-targeting treatments to standard chemotherapy led to a small improvement in QALYs for a modest increase in cost (or cost-savings). ZA and Sr89 resulted in ICERs below conventional willingness to-pay per QALY thresholds, suggesting that their addition to chemotherapy may represent a cost-effective use of resources. PMID- 27256018 TI - Nitrous oxide: The nearly 'ideal' clinical sedative. PMID- 27256019 TI - Measuring the growth rate of UK dairy heifers to improve future productivity. AB - Sub-optimal heifer growth is associated with higher disease rates and reduced future performance and longevity in the dairy herd. This report describes a system for measuring heifer growth from birth to first calving that was used on commercial dairy farms in South West England, in order to gather benchmarking data to feed back to farmers. Weights (n = 8443) were collected from 20 farms. There was a marked variation in individual and herd mean growth rates. Overall, calves gained no weight in the first 8 days after birth and had a very low growth rate (median 0.12 kg/day) up to 30 days, a period when feed conversion efficiency is high and calves are vulnerable to disease. Heifers whose growth rate up to 180 days was low were significantly less likely to achieve target service weight (374 kg) by 420 days. Monitoring heifer growth during the rearing period enables farmers to improve heifer growth rates and so impact both the efficiency of heifer rearing and, potentially, the productivity and performance of the adult herd. PMID- 27256020 TI - Prevalence and risk factors of Staphylococcus spp. carriage among dogs and their owners: A cross-sectional study. AB - This study investigated colonization and association of staphylococci between healthy dogs and their owners. In a cross-sectional study, nasal carriage and antibiotic susceptibility of isolated staphylococci were determined for 119 dogs and 107 owners. Relatedness of the Staphylococcus isolates in dogs and their owners was investigated using antibiograms, toxin profiles, and genotyping by pulsed-field gel electrophoresis (PFGE), multilocus sequence type, and spa typing. Risk factors for carriage of methicillin-resistant staphylococci in dogs were also evaluated. Staphylococcus spp. were isolated from 65 (60.7%) owners and 44 (37.0%) dogs. The following species were isolated, listed in order of decreasing frequency: S. epidermidis, S. pseudintermedius, S. aureus, S. scheiferi subsp. coagulans, S. haemolyticus, S. sciuri, S. saprophyticus and S. warneri. S. pseudintermedius (65.9%) was the major isolate in dogs while S. epidermidis (81.5%) was the major type in owners. Among the isolates, 71.6% were methicillin resistant (MR) and 95.4% of the isolates demonstrated multi-drug resistance regardless of the origin. Only one dog-owner pair shared the same Staphylococcus spp. (S. pseudintermedius); however, the organisms were of different PFGE subtypes and exhibited different antibiotic resistance and toxin profiles while both isolates displayed same sequence type (ST365). While the dog origin isolate showed spa type t02, the owner-origin isolate was negative to PCRs targeting spa gene sequence. Risk factor analysis showed that the presence of cohabitant animals was correlated with the nasal carriage of MR staphylococci in dogs. The cumulative data indicated that animal- and owner-origin staphylococci have various subtypes with high prevalence of MR; however, the bacteria are not shared between healthy dogs and their owners. PMID- 27256021 TI - Farmers' beliefs about bovine tuberculosis control in Northern Ireland. AB - Beliefs can play an important role in farmer behaviour and willingness to adopt new policies. In Northern Ireland, bovine tuberculosis (bTB) is one of the most important endemic diseases facing the cattle industry. An observational study was conducted on 192 farms in a high bTB incidence area during 2010-2011 in order to obtain a better understanding of farmers' beliefs in relation to bTB control. The views of farmers who had experienced a recent confirmed or multiple reactor bTB breakdowns (cases) were compared to those of farmers who had no recent reactors or restricted herd tests (controls). Data were obtained from a face-to-face questionnaire assessing farmers' agreement to 22 statements. All participating farmers found bTB control important and most were keen to learn more about bTB biosecurity measures and were in favour of the cattle-related bTB control measures as presented in the questionnaire (isolation of skin test inconclusive animals, use of the gamma-interferon test and pre-movement testing). The majority of farmers would allow badger vaccination and culling on their own land with an overall preference for vaccination. Highest disagreement was shown for the statements querying a willingness to pay for bTB control measures. There was agreement on most issues between case and control farmers and between different age groups of farmers although case farmers showed more support for additional advice on bTB biosecurity measures (P = 0.042). Case farmers were also more in favour of allowing badger vaccination (P = 0.008) and culling (P = 0.043) on their land and showed less concern for public opposition (P = 0.048). PMID- 27256022 TI - Combining reverse-transcription multiplex PCR and microfluidic electrophoresis to simultaneously detect seven mosquito-transmitted zoonotic encephalomyelitis viruses. AB - Several mosquito-transmitted viruses are causative agents for zoonotic encephalomyelitis. Rapid identification of these viruses in mosquito populations is an effective method for surveying these diseases. To detect multiple mosquito transmitted viral agents, including West Nile virus, Saint Louis encephalitis virus, Venezuelan equine encephalomyelitis virus, Western equine encephalomyelitis virus, Eastern equine encephalomyelitis virus, Highlands J virus and Japanese encephalitis virus, an assay using multiplex reverse transcription PCR combined with microfluidic electrophoresis was developed and evaluated. Tailed nested primers were used in the assay to amplify specific viral genomic segments, and products with specific length were further analyzed by using a microfluidic electrophoresis chip. The assay exhibited good specificity and analytical sensitivity (10(2) copies/uL). This technology can be helpful in the quarantine and surveillance of exotic encephalomyelitis viruses which are transmitted by mosquitoes. PMID- 27256023 TI - Transcriptomic analysis identified up-regulation of a solute carrier transporter and UDP glucuronosyltransferases in dogs with aggressive cutaneous mast cell tumours. AB - Gene expression analyses have been recently used in cancer research to identify genes associated with tumorigenesis and potential prognostic markers or therapeutic targets. In the present study, the transcriptome of dogs that had died because of mast cell tumours (MCTs) was characterised to identify a fingerprint having significant influence on prognosis determination and treatment selection. A dataset (GSE50433) obtained using a commercial canine DNA microarray platform was used. The transcriptome of seven biopsies obtained from dogs with histologically confirmed, surgically removed MCTs, treated with chemotherapy, and dead for MCT-related causes, was compared with the transcriptional portrait of 40 samples obtained from dogs with histologically confirmed, surgically removed MCTs and that were still alive at the end of the follow-up period. Among the differentially expressed genes (DEGs), eight transcripts were validated by quantitative real time PCR and their mRNA levels were measured in a cohort of 22 additional MCTs. Statistical analysis identified 375 DEGs (fold change 2, false discovery rate 5%). The functional annotation analysis indicated that the DEGs were associated with drug metabolism and cell cycle pathways. Particularly, members of solute carrier transporter (SLC) and UDP glucuronosyltransferase (UGT) gene families were identified as dysregulated. Principal component analysis (PCA) of the 22 additional MCTs identified the separate cluster dogs dead for MCT related causes. SLCs and UGTs have been recently recognised in human cancer as important key factors in tumour progression and chemo-resistance. An in-depth analysis of their roles in aggressive canine MCT is warranted in future studies. PMID- 27256024 TI - ERas protein is overexpressed and binds to the activated platelet-derived growth factor beta receptor in bovine urothelial tumour cells associated with papillomavirus infection. AB - Embryonic stem cell-expressed Ras (ERas) encodes a constitutively active form of guanosine triphosphatase (GTPase) that binds to and activates phosphatidylinositol 3 kinase (PI3K), which in turn phosphorylates and activates downstream targets such as Akt. The current study evaluated ERas regulation and expression in papillomavirus-associated urothelial tumours in cattle grazing on lands rich in bracken fern. ERas was found upregulated and overexpressed by PCR, real time PCR and Western blot. Furthermore, protein overexpression was also confirmed by immunohistochemistry. ERas was found to interact physically and colocalise with the activated platelet derived growth factor beta receptor (PDGFbetaR) by coimmunoprecipitation and laser scanning confocal investigations. Phosphorylation of Akt, a downstream effector both of ERas and PDGFbetaR, appeared to be increased in urothelial tumour cells. Altogether, these data indicate that ERas/PDGFbetaR complex could play a role in the pathogenesis of bovine papillomavirus-associated bladder neoplasia. PMID- 27256025 TI - A review of fibropapillomatosis in Green turtles (Chelonia mydas). AB - Despite being identified in 1938, many aspects of the pathogenesis and epidemiology of fibropapillomatosis (FP) in marine turtles are yet to be fully uncovered. Current knowledge suggests that FP is an emerging infectious disease, with the prevalence varying both spatially and temporally, even between localities in close proximity to each other. A high prevalence of FP in marine turtles has been correlated with residency in areas of reduced water quality, indicating that there is an environmental influence on disease presentation. Chelonid herpesvirus 5 (ChHV5) has been identified as the likely aetiological agent of FP. The current taxonomic position of ChHV5 is in the family Herpesviridae, subfamily Alphaherpesvirinae, genus Scutavirus. Molecular differentiation of strains has revealed that a viral variant is typically present at specific locations, even within sympatric species of marine turtles, indicating that the disease FP originates regionally. There is uncertainty surrounding the exact path of transmission and the conditions that facilitate lesion development, although recent research has identified atypical genes within the genome of ChHV5 that may play a role in pathogenesis. This review discusses emerging areas where researchers might focus and theories behind the emergence of FP globally since the 1980s, which appear to be a multi-factorial interplay between the virus, the host and environmental factors influencing disease expression. PMID- 27256026 TI - Effects of sphingolipid extracts on the morphological structure and lipid profile in an in vitro model of canine skin. AB - Ceramides (CER) are essential sphingolipids of the stratum corneum (SC) that play an important role in maintaining cutaneous barrier function. Skin barrier defects occur in both human beings and dogs affected with atopic dermatitis, and have been associated with decreased CER concentrations and morphological alterations in the SC. The aim of the present study was to investigate the changes induced by three different sphingolipid extracts (SPE-1, SPE-2 and SPE-3) on the morphological structure and lipid composition of canine skin, using an in vitro model, whereby keratinocytes were seeded onto fibroblast-embedded collagen type I matrix at the air-liquid interface. Cell cultures were supplemented with SPE-1, SPE-2, SPE-3 or vehicle (control) for 14 days. The relative concentrations of lipids were determined by ultra-performance liquid chromatography coupled to mass spectrometry. The ultrastructural morphology of samples was examined by transmission electron microscopy. SPE-1 induced significant elevation in total CERs, CER[NS], CER[NDS], CER[NP], CER[AS], CER[AP], CER[EOS] and CER[EOP] subclasses, whereas SPE-2 induced a significant elevation in total CER, CER[AP] and CER[EOS] compared with control conditions. Ultrastructural analysis revealed an increase in lamellar-lipid structures in the SC of SPE-1-treated samples. The findings demonstrated that SPE-1 stimulates production of CERs, as shown by changes in lipid composition and ultrastructural morphology. Thus, SPE-1 contributes to the formation of a well-organised SC and represents a potential therapeutic target for improving skin barrier function in atopic dermatitis. PMID- 27256027 TI - Measuring body composition in dogs using multifrequency bioelectrical impedance analysis and dual energy X-ray absorptiometry. AB - Thirty-five healthy, neutered, mixed breed dogs were used to determine the ability of multifrequency bioelectrical impedance analysis (MFBIA) to predict accurately fat-free mass (FFM) in dogs using dual energy X-ray absorptiometry (DXA)-measured FFM as reference. A second aim was to compare MFBIA predictions with morphometric predictions. MFBIA-based predictors provided an accurate measure of FFM, within 1.5% when compared to DXA-derived FFM, in normal weight dogs. FFM estimates were most highly correlated with DXA-measured FFM when the prediction equation included resistance quotient, bodyweight, and body condition score. At the population level, the inclusion of impedance as a predictor variable did not add substantially to the predictive power achieved with morphometric variables alone; in individual dogs, impedance predictors were more valuable than morphometric predictors. These results indicate that, following further validation, MFBIA could provide a useful tool in clinical practice to objectively measure FFM in canine patients and help improve compliance with prevention and treatment programs for obesity in dogs. PMID- 27256028 TI - Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs. AB - In order to determine the comparative efficacy of vaccines administered intranasally or orally to protect puppies from disease subsequent to experimental infection with Bordetella bronchiseptica (Bb), a randomized controlled trial was performed using 48 approximately 8-week-old specific pathogen free, Bb naive Beagle puppies. Puppies were randomized into three groups and administered vaccines containing Bb intranasally or orally, or a placebo intranasally. Twenty one days later, all dogs were challenge exposed via aerosol administration of Bb. Clinical signs, nasal bacterial shedding and immune responses were monitored for 28 days after challenge. Intranasally vaccinated puppies had significantly lower rates of coughing, nasal discharge, retching and sneezing (i.e. were less sick clinically) than control puppies. The distinction between the orally vaccinated puppies and the control puppies was less consistent. The orally vaccinated puppies had less coughing and less retching than the control puppies, but nasal discharge and sneezing did not differ from control animals. Orally vaccinated puppies had higher rates of coughing, nasal discharge, retching and sneezing than the intranasally vaccinated puppies. Although both intranasal and oral Bb vaccines stimulated immune responses associated with disease sparing following Bb infection, the intranasal route of delivery conferred superior clinical outcomes. The observed difference in clinical efficacy suggests the need to question the rationale for the use of currently available orally administered Bb vaccines. PMID- 27256029 TI - Potential of circulating microRNAs as biomarkers in veterinary medicine. PMID- 27256030 TI - Investigations into the seasonal presence of Mycoplasma species in fattening lambs. AB - The presence of infection with Mycoplasma species in association with lung consolidation, environmental temperature and relative humidity was investigated in 410 clinically healthy fattening lambs from five different feedlots in Extremadura (southwestern Spain). Isolates of Mycoplasma species were obtained (n= 117), including Mycoplasma ovipneumoniae (n = 18) and Mycoplasma arginini (n = 99). Two seasonal periods were identified. The first period, which included February, March, September, October, and November, had an average temperature of 17.5 +/- 4.7 degrees C and a relative humidity of 61.3 +/- 15.8%. The second seasonal period, which included the months from April to August, had an average temperature of 22.9 +/- 5.5 degrees C and a relative humidity of 48.4 +/- 10.7%. Most Mycoplasma species were isolated from the second seasonal period, indicating that higher temperatures and lower relative humidity favour the presence of Mycoplasma species. M. arginini was also associated with lung consolidation. PMID- 27256032 TI - Whilst quality research has mattered for decades, historical imperatives have been ignored. PMID- 27256031 TI - Proteinuria and lipoprotein lipase activity in Miniature Schnauzer dogs with and without hypertriglyceridemia. AB - Spontaneous hyperlipidemia in rats causes glomerular disease. Idiopathic hypertriglyceridemia (HTG) is prevalent in Miniature Schnauzers, but its relationship with proteinuria is unknown. Decreased activity of major lipid metabolism enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL), may play a role in the cyclic relationship between hyperlipidemia and proteinuria. These enzymes have also not been previously investigated in Miniature Schnauzers. The aims of this study were to determine the relationship between HTG and proteinuria in Miniature Schnauzers and to measure LPL and HL activities in a subset of dogs. Fifty-seven Miniature Schnauzers were recruited (34 with and 23 without HTG). Fasting serum triglyceride concentrations and urine protein-to-creatinine ratios (UPC) were measured in all dogs, and LPL and HL activities were determined in 17 dogs (8 with and 9 without HTG). There was a strong positive correlation between triglyceride concentration and UPC (r = 0.77-0.83, P < 0.001). Proteinuria (UPC >= 0.5) was present in 60% of dogs with HTG and absent from all dogs without HTG (P < 0.001). Proteinuric dogs were not azotemic or hypoalbuminemic. Dogs with HTG had a 65% reduction in LPL activity relative to dogs without HTG (P < 0.001); HL activity did not differ. Proteinuria occurs with HTG in Miniature Schnauzers and could be due to lipid-induced glomerular injury. Reduced LPL activity may contribute to the severity of HTG, but further assay validation is required. PMID- 27256033 TI - Tracheostomy in childhood: review of the literature on complications and mortality over the last three decades. AB - INTRODUCTION: Tracheostomy is a procedure with unique characteristics when used on pediatric patients due to the greater technical difficulty and higher morbidity and mortality rates relative to the procedure in adults. In recent decades, there have been significant changes in the medical care available to children, particularly for those who need intensive care. Surgical conditions have also improved, and there has been an advent of new equipment and medications. These advances have brought changes to both tracheostomy indications and tracheostomy complications. OBJECTIVE: To perform a review of the articles published over the last three decades on the complications and mortality associated with tracheostomies in children. METHODS: Articles were selected from the Cochrane, Latin American and Caribbean Health Sciences Literature, SciELO, National Library of Medicine (Medline Plus), and PubMed online databases. The articles selected had been published between January 1985 and December 2014, and the data was compared using the Chi-square test. RESULTS: A total of 3797 articles were chosen, 47 of which were used as the basis for this review. When the three decades were evaluated as a whole, an increase in tracheostomies in male children under one year of age was found. The most common complications during the period analyzed in descending order of frequency were granuloma, infection, and obstruction of the cannula, accidental decannulation, and post decannulation tracheocutaneous fistula. In the second and third decades of the review, granulomas represented the most common complication; in the first decade of the review, pneumothoraces were the most common. Mortality associated with tracheostomy ranged from 0% to 5.9%, while overall mortality ranged from 2.2% to 59%. In addition, the review included four studies on premature and/or very underweight infants who had undergone tracheostomies; the studies reported evidence of higher mortality in this age group to be largely associated with underlying diseases. CONCLUSION: Improved surgical techniques and intensive care, the creation of new medications, and vaccines have all redefined the main complications and the mortality rates of tracheostomy in children. It is a safe procedure that increases chances of survival in those who require the prolonged use of mechanical ventilation. PMID- 27256034 TI - Vascular sinonasal lesions. How useful is radiology in diagnosis of rare lesions? PMID- 27256035 TI - The Electronic Patient Reported Outcome Tool: Testing Usability and Feasibility of a Mobile App and Portal to Support Care for Patients With Complex Chronic Disease and Disability in Primary Care Settings. AB - BACKGROUND: People experiencing complex chronic disease and disability (CCDD) face some of the greatest challenges of any patient population. Primary care providers find it difficult to manage multiple discordant conditions and symptoms and often complex social challenges experienced by these patients. The electronic Patient Reported Outcome (ePRO) tool is designed to overcome some of these challenges by supporting goal-oriented primary care delivery. Using the tool, patients and providers collaboratively develop health care goals on a portal linked to a mobile device to help patients and providers track progress between visits. OBJECTIVES: This study tested the usability and feasibility of adopting the ePRO tool into a single interdisciplinary primary health care practice in Toronto, Canada. The Fit between Individuals, Fask, and Technology (FITT) framework was used to guide our assessment and explore whether the ePRO tool is: (1) feasible for adoption in interdisciplinary primary health care practices and (2) usable from both the patient and provider perspectives. This usability pilot is part of a broader user-centered design development strategy. METHODS: A 4-week pilot study was conducted in which patients and providers used the ePRO tool to develop health-related goals, which patients then monitored using a mobile device. Patients and providers collaboratively set goals using the system during an initial visit and had at least 1 follow-up visit at the end of the pilot to discuss progress. Focus groups and interviews were conducted with patients and providers to capture usability and feasibility measures. Data from the ePRO system were extracted to provide information regarding tool usage. RESULTS: Six providers and 11 patients participated in the study; 3 patients dropped out mainly owing to health issues. The remaining 8 patients completed 210 monitoring protocols, equal to over 1300 questions, with patients often answering questions daily. Providers and patients accessed the portal on an average of 10 and 1.5 times, respectively. Users found the system easy to use, some patients reporting that the tool helped in their ability to self-manage, catalyzed a sense of responsibility over their care, and improved patient-centered care delivery. Some providers found that the tool helped focus conversations on goal setting. However, the tool did not fit well with provider workflows, monitoring questions were not adequately tailored to individual patient needs, and daily reporting became tedious and time-consuming for patients. CONCLUSIONS: Although our study suggests relatively low usability and feasibility of the ePRO tool, we are encouraged by the early impact on patient outcomes and generally positive responses from both user groups regarding the potential of the tool to improve care for patients with CCDD. As is consistent with our user-centered design development approach, we have modified the tool based on user feedback, and are now testing the redeveloped tool through an exploratory trial. PMID- 27256036 TI - Interdisciplinary psychosocial care for families with inherited cardiovascular diseases. AB - Inherited cardiovascular diseases pose unique and complex psychosocial challenges for families, including coming to terms with life-long cardiac disease, risk of sudden death, grief related to the sudden death of a loved one, activity restrictions, and inheritance risk to other family members. Psychosocial factors impact not only mental health but also physical health and cooperation with clinical recommendations. We describe an interdisciplinary approach to the care of families with inherited cardiovascular disease, in which psychological care provided by specialized cardiac genetic counselors, nurses, and psychologists is embedded within the cardiovascular care team. We report illustrative cases and the supporting literature to demonstrate common scenarios, as well as practical guidance for clinicians working in the inherited cardiovascular disease setting. PMID- 27256037 TI - Focus on paediatrics. PMID- 27256038 TI - Severe traumatic brain injury in children: a vision for the future. PMID- 27256039 TI - Enantioselective Vinylogous Organocascade Reactions. AB - Cascade reactions are powerful tools for rapidly assembling complex molecular architectures from readily available starting materials in a single synthetic operation. Their marriage with asymmetric organocatalysis has led to the development of novel techniques, which are now recognized as reliable strategies for the one-pot enantioselective synthesis of stereochemically dense molecules. In recent years, even more complex synthetic challenges have been addressed by applying the principle of vinylogy to the realm of organocascade catalysis. The key to the success of vinylogous organocascade reactions is the unique ability of the chiral organocatalyst to transfer reactivity to a distal position without losing control on the stereo-determining events. This approach has greatly expanded the synthetic horizons of the field by providing the possibility of forging multiple stereocenters in remote positions from the catalyst's point of action with high selectivity, while simultaneously constructing multiple new bonds. This article critically describes the developments achieved in the field of enantioselective vinylogous organocascade reactions, charting the ideas, the conceptual advances, and the milestone reactions that have been essential for reaching highly practical levels of synthetic efficiency. PMID- 27256040 TI - [To strengthen the deep exploration of thyroid papillary microcarcinoma]. PMID- 27256041 TI - [Clinicopathologic study of primary angiosarcoma of thyroid]. AB - OBJECTIVE: To investigate the clinicopathologic characteristics of primary angiosarcoma in thyroid. METHODS: Three cases of primary angiosarcoma in thyoid were analyzed by gross examination, light microscopy and immunohistochemical staining, as well as related literatures were reviewed. RESULTS: The patients included 2 males and 1 female. The age of patients ranged from 52 to 78 years. The tumors showed an infiltrating histological pattern. Irregular, anastomosing gaping vascular channels were usually evident, and intravascular papillary fronds were occasionally present. In other areas, tumors featured a solid pattern of growth with cells arranged in sheets and nests with no intervening stroma. The neoplastic cells were epithelioid, spindled or polygonal-shaped with abundant eosinophilic cytoplasm and round, large, vesicular nuclei containing prominent nucleoli. The tumors showed brisk mitotic activity and necrosis. Immunohistochemical study revealed that the tumor cells were positive for CD31, ERG, Fli1, CD34, FVIIIRAg and CKpan to different extents. CONCLUSIONS: Primary epithelioid angiosarcoma of the thyroid is a rare, high-grade malignancy that may be misdiagnosed as other malignancies, especially anaplastic thyroid carcinoma. Recognizing its clinicopathologic characters and combined application of specific vascular endothelial immunohistochemical markers is important to avoid confusion with other lesions. PMID- 27256042 TI - [Fine needle aspiration cytology of thyroid nodules: a cytopathologic study of 2 043 cases]. AB - OBJECTIVE: To evaluate the clinical value of thyroid fine needle aspiration cytology(FNAC) and the Bethesda system for reporting thyroid cytopathology(TBSRTC). METHODS: FNAC was performed for 2 043 cases and cytopathological data were retrospectively analyzed. Cytopathological diagnoses according to TBSRTC were classified as non-diagnostic, benign, atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS), follicular neoplasm/suspicious for follicular neoplasm(FN/SFN), suspicious for malignancy(SM) and malignancy. The results of 234 FNAC samples in which surgery was performed were compared with the histological diagnoses. RESULTS: Of the 2 043 FNAC samples, 15.7%(320/2 043)were non-diagnostic, 51.2%(1 047/2 043)were benign, 16.6%(339/2 043) were AUS/FLUS, 2.3%(46/2 043)were FN/SFN, 8.6%(176/2 043)were SM and 5.6%(115/2 043)were malignant. In 234 cases, there was follow-up histology. Rates of malignancy were as follows: non-diagnostic, 18.2%(2/11); benign(2.2%, 1/45); AUS/FLUS(25.6%, 10/29); FN/SFN(12.1%, 10/39); SM(91.8%, 56/61); malignant(100.0%, 45/45). The sensitivity, specificity, false positive rate, false negative rate and overall accuracy of FNAC in the diagnosis of thyroid nodules was 87.1%(101/116), 95.3%(102/107), 4.7%(5/107), 12.9%(15/116), 91.0%(203/223). CONCLUSIONS: FNAC is a reliable diagnostic method for evaluation of thyroid disease. TBSRTC is a accurate and effective reporting system for cytopathological diagnoses, so it is worthy of being widely popularized in clinical application. PMID- 27256043 TI - [Expression and clinical significance of CD147 in parathyroid carcinoma]. AB - OBJECTIVE: To study the expression and clinical significance of CD147 in the patients of parathyroid carcinoma. METHODS: Fourteen cases of parathyroid carcinoma encountered during the period from 2012 to 2015 were enrolled. Thirty three cases of parathyroid adenoma encountered during the same period were enrolled. The expression of CD147 in parathyroid carcinoma and parathyroid adenoma was studied by means of immunohistochemistry (EnVision method). RESULTS: CD147 positive color was brown and yellow, and positive position was located mainly in the cytomembrane, and a small amount of cytoplasm was appeared. Among 14 cases of parathyroid carcinoma, 11 cases of CD147 positive score was 3+ , 3 cases of CD147 positive score was 2+ ; Among 33 cases of parathyroid adenoma , 8 cases of CD147 positive score was 2+ , 15 cases of it was 1+ , 10 cases of it was negative. CD147 was highly expressed in parathyroid carcinoma tissues, and the expression of CD147 was significantly different from the expression of parathyroid adenoma(P<0.05). CONCLUSION: CD147 immunohistochemical staining can help to diagnose parathyroid carcinoma. PMID- 27256044 TI - [Prognostic significance of the changes of elastic fibers in acinar predominant or papillary-predominant pulmonary adenocarcinomas]. AB - OBJECTIVE: To evaluate the role of elastic fiber changes in predicting survival outcomes in intermediate-grade lung adenocarcinoma. METHODS: All pulmonary adenocarcinoma resections conducted between January 2009 and December 2009 were reviewed. Pathologically confirmed adenocarcinomas smaller than 3 cm were included in the present study. All cases were categorized into three elastic fiber patterns (EFP): complete loss as pattern I (EFP I), partial loss as pattern II (EFP II), normal and diffusely increase as pattern III (EFP III). Patients with different EFP were compared. RESULTS: One hundred and ninety four patients were included in this study, with 67(34.5%), 70(36.1%)and 57(29.4%) cases presenting as EFP I, EFP II, and EFP III, respectively. Lymph nodal metastases occurred in 35.8% (24/67), 40.0% (28/70), and 10.5% (6/57) of EFP I, EFP II and EFP III patterns, respectively. The percentage of EFP I and II increased with increasing tumor size, these patterns occurring in 55.1% (38/69) of tumors <=2.0 cm, and 79.2% (99/125) of tumors 2.1-3.0 cm in sizes, respectively. The overall 5 year overall survival rate was 75.8%, and 67.2% for EFP I, 68.6% for EFP II, and 94.7% for EFP III. CONCLUSION: In patients with intermediate-grade lung adenocarcinoma, EFP should be formally recognized as a feature of tumor invasion, and its evaluation can help to recognize tumor invasive and access clinical prognosis. PMID- 27256045 TI - [Inflammatory fibroid polyp of the gastrointestinal tract: a clinicopathologic features of 37 cases]. AB - OBJECTIVE: To study the clinicopathologic features, pathogenesis, and differential diagnosis of inflammatory fibroid polyp (IFP) of the gastrointestinal tract. METHODS: The clinical and pathologic findings of 37 IFPs in the gastrointestinal tract were retrospectively analyzed. Immunohistochemical study and KIT, PDGFRA molecular analysis were carried out and the literatures reviewed. RESULTS: There were 9 males and 28 females. The median age was 57 (range 37 to 78) years. Twenty-two were in the antrum, nine in the ileum, three in the cardia, and one each in the gastric angle, corpora ventriculi and duodenum. The lesion ranged in size from 0.5 to 5.5 cm (mean 3 cm). Grossly, the majority appeared as a solitary non-encapsulated, submucosal, polypoid lesion. There was associated mucosal ulceration in three cases. Microscopically, the gastric lesions showed spindle-shaped cells arranged in an onion skin-like pattern around vessels and mucosal glands in a concentric formation. But the lesions in the ileum represented Vanek's tumor subtype devoid of concentric formations, with spindled to epithelioid cells dispersed in edematous stroma. Most of the lesions were in the mucosa and submucoma, but one small intestinal IFP infiltrated the muscularis propria. The inflammatory component of the lesions consisted predominantly of lymphocytes and eosinophils. Immunohistochemically, all cases displayed diffuse reactivity for vimentin and CD34; and 18 expressed PDGFRA. Analysis of KIT and PDGFRA mutations was performed in 18 cases. No KIT mutations were identified. However, four cases harbored activating mutations in PDGFRA exon 18 (D842V), five showed mutations in exon 12 (p.566 571delSPDGHEinsR). Follow-up in 30 cases showed no recurrence or metastasis. CONCLUSIONS: IFPs not only exhibit two morphologies, but also show mutations in the PDGFRA gene. IFP is a benign mesenchymal tumor rather than a reactive lesion. PMID- 27256046 TI - [Value of MDM2, CDK4 and SATB2 immunohistochemistry in histologic diagnosis of low-grade osteosarcoma]. AB - OBJECTIVE: To investigate the value of combined application of MDM2, CDK4 and SATB2 immunohistochemistry in pathological diagnosis of low-grade osteosarcoma. METHODS: Forty-seven cases of low grade osteosarcoma, including low grade central osteosarcoma (n=20) and parosteal osteosarcoma (n=27), were selected from Shanghai Jiaotong University Affiliated the Sixth People's Hospital. The clinical, radiography and histopathology were reviewed. The sensitivity and specificity of MDM2, CDK4 and SATB2 immunohistochemistry in the diagnosis of low grade osteosarcoma were assessed along with an evaluation of their expressions in fibrous dysplasia, desmoplastic fibroma, low-grade fibrosarcoma and other fibrous tumors. RESULTS: Low-grade osteosarcoma had protracted clinical course, occurring mostly in elder adults and mainly involving long bones. Radiographic studies showed that low-grade central osteosarcoma had a mainly malignant lytic presentation, however about 5/18 of tumors overlapping with intermediate and benign bone diseases, while parosteal osteosarcoma was characterized by a densely sclerotic malignant appearance. Histologically, low-grade osteosarcomas were characterized by well-differentiated spindle tumor cells, various mature tumor bones and an aggressive growth pattern. The positive expression rates of MDM2 and CDK4 in low-grade osteosarcoma were 74.5% and 55.3%, respectively. Eighty-three percent of low-grade osteosarcoma expressed one or both markers. Low-grade osteosarcoma and fibrous dysplasia were both positive for SATB2, while desmoplastic fibroma, low-grade fibrosacoma and other fibrous tumors were negative for SATB2. CONCLUSIONS: Accurate diagnosis of low-grade osteosarcoma should be based on combination of clinical presentation, imaging and histopathology, with immunohistochemistry as a diagnostic adjunct. Positive immunostaining for CDK4 and/or MDM2 supports the diagnosis of low-grade osteosarcoma, but the negative one does not rule out such lesion. The negative expression of SATB2 is helpful to exclude fibrous tumors originating from bone with the exception of fibrous dysplasia. PMID- 27256047 TI - [Comparison of HER2 gene status between primary breast cancer and synchronous axillary lymph node metastasis]. AB - OBJECTIVE: To investigate the discordant rate of HER2 gene status between primary breast cancer and synchronous axillary lymph node metastasis. METHODS: One hundred and fifty cases of primary breast cancer with corresponding synchronous lymph node metastases were collected, including 50 cases of HER2 FISH positive, 50 cases of HER2 FISH negative and 50 cases of HER2 FISH equivocal primary tumors, at Peking Union Medical College Hospital between May 2012 and June 2015. The HER2 gene status in lymph node metastatic tumors was analyzed by FISH, and the discordance of HER2 gene status was identified between primary and metastatic tumors. RESULTS: The incidence of discordant HER2 gene status between primary breast cancer and synchronous lymph node metastasis was 20.67%(31/150). Forty four FISH positive, 3 FISH equivocal and 3 FISH negative cases were found in the first group of 50 patients with HER2 positive results in primary tumor. Forty seven FISH negative, 3 FISH equivocal cases were discovered in the second group of 50 patients with HER2 negative results in primary tumor. Four FISH positive, 18 FISH negative and 28 equivocal cases were observed in the third group of 50 patients with HER2 equivocal results in primary tumor. The discordance of HER2 gene status between primary tumor and lymph node metastasis in the third group of patients was significantly higher than the other two groups (P<0.05). CONCLUSIONS: Significant discordance of HER2 gene status between the primary and lymph node metastatic tumors exists. Patients with lymph node metastasis, simultaneous testing of HER2 status may be performed in both primary breast tumor and its lymph node metastasis. HER2 status of nodal metastatic lesion may be more relevant for guiding anti-HER2 target therapy. PMID- 27256048 TI - [BRCA1/2 gene mutation and clinicopathologic features of triple negative breast cancer]. AB - OBJECTIVE: To investigate the incidence of BRCA1/2 gene mutation among triple negative breast cancer (TNBC) patients. METHODS: Polymerase chain reaction and DNA sequencing were used to detect mutations of BRCA1 (exons 2, 11 and 20) and BRCA2 (exon 11) genes using paraffin-embedded tissue samples of 33 TNBC patients (21 Uyghur patients and 12 Han patients ) in Xinjiang Uygur Autonomous Region. RESULTS: Among 33 cases of TNBC, 5 cases (5/33, 15.2%) were found to have BRCA1 gene mutation. The exon 11 of BRCA1 gene mutation proportion was seen in 4/5 and exon 20 of BRCA1 gene mutation proportion was seen in 1/5. No germline mutation was found in exon 2 of BRCA1 gene and exon 11 of BRCA2 gene. The onset age of patients with BRCA1 mutations were younger than 50 years. Four BRCA1 mutation patients were premenopausal. The proportions of BRCA1 gene mutation of Uygur TNBC patients and Han TNBC patients were 2/12 and 3/21, respectively, without significant difference (P=0.854). BRCA mutations were mainly found in stageItoII (4/5) and only 1 case (1/5) was found with stage III disease. No significant difference was found in fertility status, menstrual status and age at menarche between mutated and non-mutated patients (P>0.05) . CONCLUSIONS: Germline mutation of BRCA1 may be more often associated with TNBC than BRCA2 for its higher mutation rate. Compared with non-mutated TNBC cases, several clinicopathologic features could be identified among mutated cases. PMID- 27256049 TI - [Roles of glucose-regulated protein 78 in proliferation and migration of human colorectal carcinoma cell line RKO]. AB - OBJECTIVE: To investigate the roles of glucose regulated protein 78(GRP78) in proliferation and migration of human colorectal carcinoma cell RKO. METHODS: The colorectal carcinoma cell line RKO was transfected by lentiviral vector pLV-shRNA GRP78 and lentivirus vector pLV-control. MTT test and colony formation assay were used to evaluate the cell proliferation ability. Distribution of cell cycle was analyzed by flow cytometry. Cell migration ability was detected by scratches migration experiment. In vivo tumorigenicity ability was measured using subcutaneous tumor assay. Differentially expressed genes were detected by Affymetrix human genome-wide expression profile chip and confirmed by Western blot analysis. RESULTS: Compared with the negative vector transfection group, cell proliferation was inhibited in vitro and in vivo (P<0.05), while there was no significant difference in migration (P>0.05). Flow cytometry results showed that silencing GRP78 resulted in a significant increase in the proportion of cells in G1 phase, while the proportion of cells in S phase was significantly lower (P<0.05). The gene chip results showed that 397 genes were differentially expressed by at least 1.2 folds in GRP78 knocked-out RKO cells, including 258 up regulated and 139 down-regulated ones. Bioinformatics analysis identified 3 genes (CDKN2B, MTOR and BIRC3) with specific expression in GRP78 down-regulated RKO cells, and the result was verified by Western blot. CONCLUSIONS: GRP78 knock-out inhibits the proliferation and growth of colorectal cancer cell, but has no obvious effect on migration invasion. Down regulation of GRP78 results in expression changes of lots of genes in RKO cells. GRP78 may exert its role in proliferation of RKO cell through regulating these genes. PMID- 27256050 TI - [Expression and clinical significance of epidermal growth factor receptor,HER2, PI3Kp110alpha and PI3Kp110beta in gastric carcinoma]. PMID- 27256051 TI - [CD24 down-regulation in non-small cell lung cancer prolongs patient survival]. PMID- 27256052 TI - [Clinicopathologic features and molecular genetics of alveolar rhabdomyosarcoma]. PMID- 27256053 TI - [Analysis of the first national "Huaxiabei" frozen section competition]. PMID- 27256054 TI - [Thyroid follicular tumor with fibrous capsule]. PMID- 27256055 TI - [Fetal heart failure caused by maternal hyperthyroidism:report of a case]. PMID- 27256056 TI - [Schwannoma of the thyroid gland: report of a case]. PMID- 27256057 TI - [Ectopic thyroid in adrenal gland:report of a case]. PMID- 27256058 TI - [Biologic behavior of thyroid carcinoma in indeterminate category of fine needle aspirates]. PMID- 27256059 TI - [Research progress on triage of ASC-US in cervical cytology]. PMID- 27256060 TI - [Community-acquired pneumonia: Incidence rate in Madrid. ATENAS study]. PMID- 27256061 TI - The agony of choice in dermatophyte diagnostics-performance of different molecular tests and culture in the detection of Trichophyton rubrum and Trichophyton interdigitale. AB - Dermatophytosis caused by dermatophytes of the genera Trichophyton and Microsporum belong to the most frequent mycoses worldwide. Molecular detection methods proved to be highly sensitive and enable rapid and accurate detection of dermatophyte species from clinical specimens. For the first time, we compare the performance of different molecular methods with each other and with conventional diagnostics in the detection of dermatophytoses caused by Trichophyton rubrum and Trichophyton interdigitale in clinical specimens (nail, skin and hair). The compared molecular methods comprise two already published PCR-ELISAs, a published quantitative RT-PCR as well as a newly developed PCR-ELISA targeting the internal transcribed spacer region. We investigated the sensitivity of the assays by analysing 375 clinical samples. In 148 specimens (39.5%) a positive result was gained in at least one of the four molecular tests or by culture, but the number of detected agents differed significantly between some of the assays. The most sensitive assay, a PCR-ELISA targeting a microsatellite region, detected 81 T. rubrum infections followed by an internal transcribed spacer PCR-ELISA (60), quantitative RT-PCR (52) and a topoisomerase II PCR-ELISA (51), whereas cultivation resulted in T. rubrum identification in 37 samples. The pros and cons of all four tests in routine diagnostics are discussed. PMID- 27256062 TI - Lower sensitivity of serum (1,3)-beta-d-glucan for the diagnosis of candidaemia due to Candida parapsilosis. AB - The aim of this study was to evaluate the sensitivity and the levels of 1,3-beta d-glucan (BDG) among patients with candidaemia due to different Candida species. Retrospective study of all patients who had a single-species candidaemia and BDG testing performed within 48 h from the onset of candidaemia during 2009-2015 was performed. Factors influencing the sensitivity of BDG, including the presence of a central venous catheter, antifungal therapy and Candida species, were analysed in univariate and multivariate models. In all, 107 patients with the following Candida distribution were included: 46 (43%) Candida albicans, 37 (35%) Candida parapsilosis, and 24 (22%) other species. BDG sensitivity and levels were the highest in C. albicans candidaemia and lowest for C. parapsilosis (respectively, 72% and 410 pg/mL for C. albicans, 41% and 39 pg/mL for C. parapsilosis, and 63% and 149 pg/mL for other species; p 0.015 and p 0.003). In multivariate analysis, Candida species (parapsilosis versus others) was the only factor influencing the sensitivity of BDG (OR 0.3, 95% CI 0.1-0.7, p 0.006). The sensitivity of BDG in candidaemia seems highly dependent on the fungal species, with the lowest being for C. parapsilosis. PMID- 27256063 TI - A dynamic relationship between mucosal T helper type 17 and regulatory T-cell populations in nasopharynx evolves with age and associates with the clearance of pneumococcal carriage in humans. AB - Pneumococcal carriage is common in young children, which may account for the high incidence of disease in this age group. Host factors determining the clearance of carriage in humans remain unclear. We aimed to study the relationships between T helper type 17 (Th17) and Foxp3(+) regulatory T (Treg) cells in nasopharynx associated lymphoid tissue (NALT) and carriage in children and adults. Frequencies of Th17 and Treg cells in NALT were analysed by flow cytometry in association with age and pneumococcal carriage status. Cytokine responses following pneumococcal stimulation were analysed by cytometric beads array. The frequencies of Th17 and Treg cells in NALT were inversely correlated (R -0.60). Whereas Treg cell frequency decreased with age (R -0.63), both Th17 and the Th17: Treg ratio increased with age (R 0.62 and R 0.64, respectively). Also, the Th17: Treg ratio was higher in carriage-negative than in carriage-positive children (p <0.01). Pneumococcal stimulation of tonsillar cells increased both Th17 and Treg cell numbers, but the Th17: Treg ratio and pattern of cytokine responses differed between carriage-negative and carriage-positive children. The former showed markedly higher Th17: Treg and interleukin-17A: interleukin-10 ratios than in the latter (p <0.01). Pneumococcal stimulation also induces Th17, although the capacity of this Th17 differentiation from naive T cells of young children was low, but increased with age. We demonstrated a dynamic relationship between Th17 and Treg cells in human nasopharynx that evolves with age. The balance between Th17 and Treg cells in NALT appears to be a major host factor closely associated with the clearance of Streptococcus pneumoniae from the nasopharynx. PMID- 27256064 TI - Dose and duration of intraventricular antibiotic therapy in meningitis. PMID- 27256065 TI - A case report of SPG11 mutations in a Chinese ARHSP-TCC family. AB - BACKGROUND: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a complicated form of hereditary spastic paraplegia, characterized by progressive spastic paraplegia, weakness of the lower extremities and is usually accompanied by mental retardation. Mutations in the Spastic Paraplegia gene 11 (SPG11) account for a large proportion of ARHSP-TCC cases worldwide. CASE PRESENTATION: We describe a Chinese family with ARHSP-TCC. Two daughters of this family presented with a spastic gait and cognitive impairment. Brain imaging of the index patient revealed a thin corpus callosum. We performed detailed physical and auxiliary examinations and were able to exclude acquired causes of spastic paraplegia. To determine the causative mutation, we took a candidate gene approach and screened the coding sequence and some flanking intronic sequence of SPG11 by direct Sanger sequencing. We identified two novel compound heterozygous mutations in SPG11 in affected individuals (c.1551_1552delTT, p.Cys518SerfsTer39 and c.5867-1G > T (IVS30-1G > T), p.Thr1956ArgfsTer15). Bioinformatic analysis predicts that these mutations would lead to a loss of protein function due to the truncation of the SPG11 protein. CONCLUSIONS: The results of this case report indicate a broader approach to include screening for SPG11 mutations in ARHSP-TCC patients. Our findings enrich the phenotypic spectrum of SPG11 mutations. PMID- 27256066 TI - Group calls for more to be done to tackle corruption in the pharmaceutical industry. PMID- 27256067 TI - Predictors of coronary artery disease in middle-aged Taiwanese women at premenopause, postmenopause and after undergoing hysterectomy. AB - AIMS AND OBJECTIVES: To examine the predictors of coronary artery disease among middle-aged women at various menopausal statuses. BACKGROUND: Few studies have explored coronary artery disease predictors among middle-aged women at various menopausal statuses, particularly with the inclusion of women who underwent a hysterectomy. DESIGN: A cross-sectional design was adopted. METHODS: Two hundred and twenty-five middle-aged women who were waiting for catheterisation examinations because of possible coronary artery disease were selected. These patients were divided into premenopausal (n = 41), postmenopausal (n = 143) and women who had undergone a hysterectomy groups (n = 41). The differences in the risk factors for coronary artery disease between patients with coronary artery disease (catheterisation results showing stenosis of >50% in at least one major coronary artery) and those without coronary artery disease in the three groups were compared. RESULTS: The participants were aged 56.8 +/- 5.9 years. In the premenopausal group, the odds of coronary artery disease among ever or current smokers was 8.46 times the odds of coronary artery disease for the never smokers. In the postmenopausal group, the odds of coronary artery disease among diabetes patients was 2.89 times the odds of coronary artery disease for those without diabetes. Each additional point on the Chinese Beck Depression Inventory-II increased the risk of coronary artery disease by 5%. In the hysterectomy group, each additional increase in 1 mmHg in systolic blood pressure increased the risk of coronary artery disease by 4%. CONCLUSIONS: Smoking, diabetes, depression and systolic blood pressure are predictors of coronary artery disease in middle-aged women at premenopause, postmenopause and after undergoing hysterectomy respectively. RELEVANCE TO CLINICAL PRACTICE: These results are beneficial for middle-aged women at various menopausal stages to effectively implement prevention of coronary artery disease. These findings were among women being evaluated for possible coronary artery disease, we suggest the need for further study in lager, longitudinal studies. PMID- 27256068 TI - Unexpected versus all-cause mortality as the endpoint for investigating the effects of a Rapid Response System in hospitalized patients. AB - BACKGROUND: The purpose of this study was to assess the effect of replacing all cause mortality by death without limitation of medical treatments (LOMT) as the endpoint in a study of rapid response teams (RRTs) in hospitalized patients. We also described the time course of LOMT orders in patients dying on a general ward and the influence of RRTs on such orders. METHODS: This study is a secondary analysis of the COMET trial, a pragmatic prospective Dutch multicenter before after study. We repeated the original analysis of the influence of RRTs on death before hospital discharge by replacing all-cause mortality by death without an LOMT order. In a subgroup of all patients dying before hospital discharge, we documented patient demographics, admission characteristics and LOMT orders of each patient. Patients age 18 ears or above were included. RESULTS: In total, 166,569 patients were included in the study. The unadjusted ORs were 0.865 (95 % CI 0.77-0.98) in the original analysis using all-cause mortality and 0.557 (95 % CI 0.40-0.78) when choosing death without LOMT as the endpoint. In total, 3408 patients died before discharge. At time of death, 2910 (85 %) had an LOMT order. Median time from last change in LOMT status and death was 2 days (IQR 1-5) in the before-phase and median time after introduction of the RRT was 1 day (IQR 1-4) (p value not significant). CONCLUSIONS: The improvement in survival of hospitalized patients after introduction of a rapid response team in the COMET study was more pronounced when choosing death without limitation of medical treatment, rather than all deaths as the endpoint. Most patients who died during hospitalization had limitation of medical treatments ordered, often shortly before death. Rapid response teams did not influence the institution of limitation of medical treatments. PMID- 27256069 TI - Physical Therapist-Led Ambulatory Rehabilitation for Patients Receiving CentriMag Short-Term Ventricular Assist Device Support: Retrospective Case Series. AB - BACKGROUND AND PURPOSE: Short-term ventricular assist device (VAD) support is used in the intensive care unit (ICU) to support individuals in end-stage heart failure prior to heart transplantation or implantation of a long-term left VAD. The literature investigating the feasibility, safety, and content of rehabilitation for this patient group is lacking. This report retrospectively describes the rehabilitation strategy, safety measures used, and nature of any adverse events and, therefore, the feasibility of this practice. CASE SERIES DESCRIPTION: Ten individuals (80% male) admitted to the ICU in critical cardiogenic shock required support via a short-term VAD. A prerehabilitation risk assessment was used to reduce the risk of cannula dislodgement. The therapeutic strategy was a stepwise progression of exercises, mobilization, and ambulation. OUTCOMES: Retrospective inspection of the case notes showed 330 rehabilitation sessions (X=33, SD=18.1, range=16-72) were performed and progressed to ambulation on 71 occasions (X=7.1, SD=7.7, range=1-27). Distance ambulated ranged from 7 to 1,200 m (X=157.7, SD=367.3). The Chelsea Critical Care Physical Assessment Tool (CPAx) score for 7 patients improved from a median of 0 (interquartile range=0-1) on day 1 to a median peak score of 39 (interquartile range=37-42). There were 8 episodes of minor adverse events (2.4% incidence rate), including 7 of transient low VAD flows. There were no major adverse events. DISCUSSION: Early rehabilitation and ambulation of recipients of short-term VAD support was safe and feasible. Recipients demonstrated improvements in physical function (CPAx score) while the VAD was in situ. PMID- 27256070 TI - Application of Intervention Mapping to the Development of a Complex Physical Therapist Intervention. AB - BACKGROUND: Physical therapist interventions, such as those designed to change physical activity behavior, are often complex and multifaceted. In order to facilitate rigorous evaluation and implementation of these complex interventions into clinical practice, the development process must be comprehensive, systematic, and transparent, with a sound theoretical basis. Intervention Mapping is designed to guide an iterative and problem-focused approach to the development of complex interventions. PURPOSE: The purpose of this case report is to demonstrate the application of an Intervention Mapping approach to the development of a complex physical therapist intervention, a remote self management program aimed at increasing physical activity after acquired brain injury. CASE DESCRIPTION: Intervention Mapping consists of 6 steps to guide the development of complex interventions: (1) needs assessment; (2) identification of outcomes, performance objectives, and change objectives; (3) selection of theory based intervention methods and practical applications; (4) organization of methods and applications into an intervention program; (5) creation of an implementation plan; and (6) generation of an evaluation plan. The rationale and detailed description of this process are presented using an example of the development of a novel and complex physical therapist intervention, myMoves-a program designed to help individuals with an acquired brain injury to change their physical activity behavior. CONCLUSION: The Intervention Mapping framework may be useful in the development of complex physical therapist interventions, ensuring the development is comprehensive, systematic, and thorough, with a sound theoretical basis. This process facilitates translation into clinical practice and allows for greater confidence and transparency when the program efficacy is investigated. PMID- 27256071 TI - Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4 mediated suppression of yes-associated protein. AB - The pH of extracellular fluids is a basic property of the tissue microenvironment and is normally maintained at 7.40 +/- 0.05 in humans. Many pathological circumstances, such as ischemia, inflammation, and tumorigenesis, result in the reduction of extracellular pH in the affected tissues. In this study, we reported that the osteogenic differentiation of BMSCs was significantly inhibited by decreases in the extracellular pH. Moreover, we demonstrated that proton-sensing GPR4 signaling mediated the proton-induced inhibitory effects on the osteogenesis of BMSCs. Additionally, we found that YAP was the downstream effector of GPR4 signaling. Our findings revealed that the extracellular pH modulates the osteogenic responses of BMSCs by regulating the proton-sensing GPR4-YAP pathway. PMID- 27256072 TI - Adult microbiota-deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus. AB - Increasing evidence implicates the microbiota in the regulation of brain and behaviour. Germ-free mice (GF; microbiota deficient from birth) exhibit altered stress hormone signalling and anxiety-like behaviours as well as deficits in social cognition. Although the mechanisms underlying the ability of the gut microbiota to influence stress responsivity and behaviour remain unknown, many lines of evidence point to the amygdala and hippocampus as likely targets. Thus, the aim of this study was to determine if the volume and dendritic morphology of the amygdala and hippocampus differ in GF versus conventionally colonized (CC) mice. Volumetric estimates revealed significant amygdalar and hippocampal expansion in GF compared to CC mice. We also studied the effect of GF status on the level of single neurons in the basolateral amygdala (BLA) and ventral hippocampus. In the BLA, the aspiny interneurons and pyramidal neurons of GF mice exhibited dendritic hypertrophy. The BLA pyramidal neurons of GF mice had more thin, stubby and mushroom spines. In contrast, the ventral hippocampal pyramidal neurons of GF mice were shorter, less branched and had less stubby and mushroom spines. When compared to controls, dentate granule cells of GF mice were less branched but did not differ in spine density. These findings suggest that the microbiota is required for the normal gross morphology and ultrastructure of the amygdala and hippocampus and that this neural remodelling may contribute to the maladaptive stress responsivity and behavioural profile observed in GF mice. PMID- 27256073 TI - Excessive Activation of TGFbeta by Spinal Instability Causes Vertebral Endplate Sclerosis. AB - Narrowed intervertebral disc (IVD) space is a characteristic of IVD degeneration. EP sclerosis is associated with IVD, however the pathogenesis of EP hypertrophy is poorly understood. Here, we employed two spine instability mouse models to investigate temporal and spatial EP changes associated with IVD volume, considering them as a functional unit. We found that aberrant mechanical loading leads to accelerated ossification and hypertrophy of EP, decreased IVD volume and increased activation of TGFbeta. Overexpression of active TGFbeta in CED mice showed a similar phenotype of spine instability model. Administration of TGFbeta Receptor I inhibitor attenuates pathologic changes of EP and prevents IVD narrowing. The aberrant activation of TGFbeta resulting in EPs hypertrophy induced IVD space narrowing provides a pharmacologic target that could have therapeutic potential to delay DDD. PMID- 27256074 TI - The Use of Polyethylene Glycol in Mammalian Herbivore Diet Studies: What Are We Measuring? AB - Polyethylene glycol (PEG) has been used to study the intake and digestion of tannin-rich plants by mammalian herbivores because it preferentially binds to tannins. However, it is not clear whether the responses of herbivores to dietary PEG is due to increased protein availability from the release of tannin-bound protein, amelioration of tannin effects, or whether PEG also may bind to other compounds and change their activity in the gut. We used three native New Zealand tree species to measure the effect of PEG on the amount of foliage eaten by invasive common brushtail possums (Trichosurus vulpecula) and on in vitro digestible nitrogen (available N). The addition of PEG increased the in vitro available N content of Weinmannia racemosa foliage, and possums ate significantly more PEG-treated foliage than untreated foliage. However, possums also ate more PEG-treated Fuchsia excorticata foliage, even though PEG did not increase in vitro available N in this species. Possums ate very little Melicytus ramiflorus, regardless of PEG treatment, even though M. ramiflorus contained the highest concentration of in vitro available N. These results prompted us to use PEG and a protein supplement, casein, to manipulate the available N concentration of diets containing ground eucalypt foliage, a well-studied food species for possums. Again, the response of possums to PEG was independent of changes in in vitro available N. In addition, altering the protein content of the diet via the addition of casein did not affect how much food the possums consumed. We conclude that the effects of PEG on dry matter intake by mammalian herbivores are not due solely to the release of tannin-bound protein. There is need for a better understanding of PEG-tannin interactions in order to ensure that the use of PEG in nutritional studies does not outstrip an understanding of its mechanisms of action. PMID- 27256075 TI - Nicotine inhibits activation of microglial proton currents via interactions with alpha7 acetylcholine receptors. AB - Alpha 7 subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in microglia and are involved in the suppression of neuroinflammation. Over the past decade, many reports show beneficial effects of nicotine, though little is known about the mechanism. Here we show that nicotine inhibits lipopolysaccharide (LPS) induced proton (H+) currents and morphological change by using primary cultured microglia. The H+ channel currents were measured by whole-cell patch clamp method under voltage-clamp condition. Increased H+ current in activated microglia was attenuated by blocking NADPH oxidase. The inhibitory effect of nicotine was due to the activation of alpha7 nAChR, not a direct action on the H+ channels, because the effects of nicotine was cancelled by alpha7 nAChR antagonists. Neurotoxic effect of LPS-activated microglia due to inflammatory cytokines was also attenuated by pre-treatment of microglia with nicotine. These results suggest that alpha7 nAChRs in microglia may be a therapeutic target in neuroinflammatory diseases. PMID- 27256076 TI - Medium-grade tubular proteinuria is common in HIV-positive patients and specifically associated with exposure to tenofovir disoproxil Fumarate. AB - OBJECTIVES: The aim of this cross-sectional study was to evaluate the prevalence and risk factors of medium-grade proteinuria (100-500 mg/g creatinine) among HIV positive adults. METHODS: Spot urine samples of HIV-positive adults without known renal disease were analyzed quantitatively between January 2009 and February 2011. Demographic and medical data were collected. Multivariate regression models for different patterns of proteinuria were constructed. RESULTS: Among 411 patients, 18 (4.4 %) presented albuminuria >300 mg/g creatinine and/or proteinuria >500 mg/g creatinine and were excluded from further analyses. Among the study population of 393 patients, 181 (46.1 %) had no significant proteinuria or albuminuria (<100 and <30 mg/g creatinine, respectively), 60 (15.3 %) had moderate albuminuria, while 152 (38.7 %) had proteinuria without albuminuria, suggesting tubular proteinuria. Independent predictors for medium-grade tubular proteinuria in multivariate analysis were exposure to tenofovir (DF), a CD4 nadir <500/ul, older age, and anti-HCV-antibodies. There was no association with classic renal risk factors like diabetes mellitus and arterial hypertension, or with estimated glomerular filtration rate (eGFR). CONCLUSIONS: We detected significant proteinuria in 230 (56.0 %) of 411 HIV-positive patients. Among this group, 152 (66.1 %) had medium-grade proteinuria without albuminuria, which was significantly associated with exposure to tenofovir, older age, a lower CD4 nadir and Hepatitis C. Nephrologic or HIV treatment guidelines fail to detect most of these patients but rather identify patients with high cardiovascular risk. In the absence of an association with eGFR the role of medium-grade tubular proteinuria as a potential early marker of chronic kidney disease remains unclear. Prospective studies are needed. PMID- 27256077 TI - Applying different mathematical variability methods to identify older fallers and non-fallers using gait variability data. AB - BACKGROUND: The clinical assessment of gait variability may be a particularly powerful tool in the screening of older adults at risk of falling. Measurement of gait variability is important in the assessment of fall risk, but the variability metrics used to evaluate gait timing have not yet been adequately studied. OBJECTIVES: The aims of this study were (1) to identify the best mathematical method of gait variability analysis to discriminate older fallers and non-fallers and (2) to identify the best temporal, kinematic parameter of gait to discriminate between older fallers and non-fallers. METHODS: Thirty-five physically active volunteers participated in this study including 16 older women fallers (69.6 +/- 8.1 years) and 19 older women non-fallers (66.1 +/- 6.2 years). Volunteers were instructed to walk for 3 min on the treadmill to record the temporal kinematic gait parameters including stance time, swing time and stride time by four footswitches sensors placed under the volunteers' feet. Data analysis used 40 consecutive gait cycles. Six statistical methods were used to determine the variability of the stance time, swing time and stride time. These included: (1) standard deviation of all the time intervals; (2) standard deviation of the means of these intervals taken every five strides; (3) mean of the standard deviations of the intervals determined every five strides; (4) root mean-square of the differences between intervals; (5) coefficient of variation calculated as the standard deviation of the intervals divided by the mean of the intervals; and (6) a geometric method calculated based on the construction of a histogram of the intervals. RESULTS: The standard deviation of 40 consecutive gait cycles was the most sensitive (100 %) and specificity (100 %) parameter to discriminate older fallers and non-fallers. CONCLUSION: The standard deviation of stance time is the kinematic gait variability parameter that demonstrated the best ability to discriminate older fallers from non-fallers. PROTOCOL NUMBER OF BRAZILIAN REGISTRY OF CLINICAL TRIALS: RBR-6rytw2. PMID- 27256078 TI - The role of DXA in sarcopenia. AB - Sarcopenia is a condition characterized by progressive and generalized reduction in skeletal muscle mass and muscle strength, associated with an increased risk of adverse outcomes (disability, hospitalization, death). The growing attention in the last years, aiming to establish a consensus definition and treatment, reflects the interest of the scientific community toward this complex condition, which has many implications in clinical practice and public health. Dual-energy X ray absorptiometry (DXA) is the gold-standard technique in the analysis of body composition at molecular level, providing assessment and quantification of fat mass, lean mass and bone mineral content, both in a single body region of interest and at whole-body level. In particular, through the assessment of non bone lean mass parameters, such as appendicular lean mass adjusted for BMI or height (ALM/BMI and ALM/ht2, respectively), it is possible to discriminate subjects with "physiological" loss of muscle mass from those with "pathological" impoverishment of this compartment, referring to specific cutoff values validated in the literature, but keeping in mind the lack of standardization of DXA measures. In addition, it is useful in treatment planning, estimating resting energy expenditure, and in follow-up, because it allows quantifying with high reproducibility the modifications in BC, distinguishing when the change is biological (deterioration due to a progression of the disease or improvement due to treatment). Due to DXA favorability in terms of accuracy, simplicity, availability, low cost and low radiation exposure, its role in sarcopenia diagnosis is becoming increasingly important, emerging as reference assessment technique in muscle mass evaluation. PMID- 27256079 TI - Correlations between the levels of acute infection markers and serum albumin in elderly patients with hip fracture. AB - OBJECTIVE: The aim of this study was to explore a clinical index that could predict the decline of serum albumin (ALB) in elderly patients (over 60 years old) with hip fractures in 2014. METHODS: All the data came from the retrospective survey, and the correlations between the ALB changes and acute infection markers were then analyzed using correlation analysis. The changes of infection markers and ALB before and after surgery were compared using the t test. RESULTS: There was no correlation of the serum ALB blood with interleukin-6 (IL-6) (r = 0.072, P = 0.588), C-reactive protein (CRP) (r = -0.249, P = 0.057), or calcitonin (PCT) (r = -0.038, P = 0.775) when patients were admitted, but it was negatively correlated with the total amount of infection markers (TAIMs) (r = -0.301, P = 0.020). The postoperative levels of IL-6 (154.23 +/- 177.14 pg/mL) (P < 0.001), CRP (69.52 +/- 39.84 mg/L) (P < 0.001), and PCT (1.27 +/- 2.4 ng/mL) (P < 0.001) were significantly increased than those before surgery [IL-6 (44.96 +/- 54.58 pg/mL), CRP (31.78 +/- 29.90 mg/L), and PCT (0.42 +/- 1.06 ng/mL)]. The postoperative level of serum ALB (29.93 +/- 3.02 g/L) was significantly reduced than that before surgery (33.95 +/- 3.69 g/L) (P < 0.001). The serum ALB level was negatively correlated with IL-6 (r = -0.333, P = 0.015) before surgery, but not correlated with TAIMs (r = -0.256, P = 0.061). The serum ALB level was negatively correlated with IL-6 (r = -0.292, P = 0.034) and TAIMs (r = -0.271, P = 0.050) after surgery. CONCLUSIONS: The serum IL-6 level could predict the changes of ALB during the disease process. PMID- 27256080 TI - Acute effects of exergames on cognitive function of institutionalized older persons: a single-blinded, randomized and controlled pilot study. AB - BACKGROUND: Improvements on balance, gait and cognition are some of the benefits of exergames. Few studies have investigated the cognitive effects of exergames in institutionalized older persons. AIMS: To assess the acute effect of a single session of exergames on cognition of institutionalized older persons. METHODS: Nineteen institutionalized older persons were randomly allocated to Wii (WG, n = 10, 86 +/- 7 year, two males) or control groups (CG, n = 9, 86 +/- 5 year, one male). The WG performed six exercises with virtual reality, whereas CG performed six exercises without virtual reality. Verbal fluency test (VFT), digit span forward and digit span backward were used to evaluate semantic memory/executive function, short-term memory and work memory, respectively, before and after exergames and Delta post- to pre-session (absolute) and Delta % (relative) were calculated. Parametric (t independent test) and nonparametric (Mann-Whitney test) statistics and effect size were applied to tests for efficacy. RESULTS: VFT was statistically significant within WG (-3.07, df = 9, p = 0.013). We found no statistically significant differences between the two groups (p > 0.05). Effect size between groups of Delta % (median = 21 %) showed moderate effect for WG (0.63). DISCUSSION: Our data show moderate improvement of semantic memory/executive function due to exergames session. It is possible that cognitive brain areas are activated during exergames, increasing clinical response. CONCLUSION: A single session of exergames showed no significant improvement in short-term memory, working memory and semantic memory/executive function. The effect size for verbal fluency was promising, and future studies on this issue should be developed. PROTOCOL NUMBER OF BRAZILIAN REGISTRY OF CLINICAL TRIALS: RBR-6rytw2. PMID- 27256081 TI - Self-directed learning can outperform direct instruction in the course of a modern German medical curriculum - results of a mixed methods trial. AB - BACKGROUND: Modernised medical curricula in Germany (so called "reformed study programs") rely increasingly on alternative self-instructed learning forms such as e-learning and curriculum-guided self-study. However, there is a lack of evidence that these methods can outperform conventional teaching methods such as lectures and seminars. This study was conducted in order to compare extant traditional teaching methods with new instruction forms in terms of learning effect and student satisfaction. METHODS: In a randomised trial, 244 students of medicine in their third academic year were assigned to one of four study branches representing self-instructed learning forms (e-learning and curriculum-based self study) and instructed learning forms (lectures and seminars). All groups participated in their respective learning module with standardised materials and instructions. Learning effect was measured with pre-test and post-test multiple choice questionnaires. Student satisfaction and learning style were examined via self-assessment. RESULTS: Of 244 initial participants, 223 completed the respective module and were included in the study. In the pre-test, the groups showed relatively homogenous scores. All students showed notable improvements compared with the pre-test results. Participants in the non-self-instructed learning groups reached scores of 14.71 (seminar) and 14.37 (lecture), while the groups of self-instructed learners reached higher scores with 17.23 (e-learning) and 15.81 (self-study). All groups improved significantly (p < .001) in the post test regarding their self-assessment, led by the e-learning group, whose self assessment improved by 2.36. CONCLUSIONS: The study shows that students in modern study curricula learn better through modern self-instructed methods than through conventional methods. These methods should be used more, as they also show good levels of student acceptance and higher scores in personal self-assessment of knowledge. PMID- 27256082 TI - Don't miss it, it might be a hydatid cyst in the gluteus. AB - Hydatid cyst is one of the five most diagnosed zoonotic diseases in the Mediterranean region. However, intramuscular localisation is very rare. It is reported that muscular involvement constitutes 1-5.4% of all Echinococcus infections. Here we would like to report an unusual case of hydatid cyst in the gluteus muscle, which had been treated with both surgical and medical treatment. PMID- 27256083 TI - Isolated tubercular hypoglossal nerve paralysis. AB - Hypoglossal nerve palsy is not an uncommon neurological finding but primary nasopharyngeal tuberculosis (TB) presenting as hypoglossal nerve palsy is very rare. A 31-year-old woman presented with headache and progressive tongue deviation towards the right side. Diagnostic nasal endoscopy revealed soft tissue mass lesion on the posterior wall of nasopharynx while MRI revealed isointense tumour in nasopharynx with normal hypoglossal nerve and brain. Histopathological examination found TB. We discuss the clinical challenges and possible pathogenesis of this rare clinical entity. PMID- 27256084 TI - Long-term outcomes of destructive seronegative (rheumatoid) arthritis - description of four clinical cases. AB - BACKGROUND: Seronegative rheumatoid arthritis is associated with a milder course of progression compared to seropositive disease. However, long-term follow-up data of the clinical course of seronegative rheumatoid arthritis are sparse. Here we describe four cases with a rare disease entity of aggressive destructive seronegative (rheumatoid) arthritis with 20-35 years of follow-up. CASE PRESENTATION: The four cases are women with an initial presentation of seronegative rheumatoid arthritis in 1980-1996 and have received disease modifying anti-rheumatic drugs since the diagnosis. In all cases, the condition has been refractory to treatments and evolved into a severe disease with destructions of the wrists, sub-talar and ankle joints, as well as large joints but not small joints of fingers and toes. All cases are negative with regard to rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antibodies against carbamylated proteins. CONCLUSIONS: This report adds to the existing literature, making the reader aware of this sub-type of inflammatory arthritis which despite being seronegative, can have devastating disease consequences. The report highlights the need for further research into this field in order to better understand this disease sub-type, the pathogenesis, disease course and outcomes. PMID- 27256086 TI - Effect of sex and age on the association between suicidal behaviour and obesity in Korean adults: a cross-sectional nationwide study. AB - OBJECTIVES: To examine the hypothesis that the relationship between obesity and the risk of suicidal behaviour would differ according to sex and age. SETTING: Data from the 2007-2012 Korean National Health and Nutrition Examination Survey (KNHANES) were used. PARTICIPANTS: 36 211 adults with body mass index (BMI) data were included and the mean age was 49.6 years. INDEPENDENT VARIABLE: BMI. PRIMARY AND SECONDARY OUTCOME MEASURES: Suicide ideation and attempts. DESIGN AND ANALYSIS: A cross-sectional study was performed. Multiple logistic regressions after controlling for socioeconomic variables and concomitant diseases were applied to see the relationship between obesity level and suicidal ideation or attempt. RESULTS: Women with severe obesity had the highest prevalence of suicide attempts and ideation, whereas among males, underweight men had the highest prevalence. After adjustment, obese men had a lower OR for suicide ideation (OR=0.87, 95% CI 0.76 to 1.00). Among women, the ORs of severely obese and underweight women were 1.27 (95% CI 1.06 to 1.52) and 1.24 (95% CI 1.06 to 1.45), respectively. When grouped by age category, the ORs for suicide ideation in severely obese women aged 18 to <30 years or attempts in severely obese women aged 30 to <50 years were 2.30 (95% CI 1.36 to 3.89) and 3.07 (95% CI 1.50 to 6.31), respectively. However, overweight and obese women aged more than 50 years exhibited significantly less ORs of suicide ideation, when compared with counterparts of normal weight. CONCLUSIONS: The association between obesity and suicidal behaviour exhibited a different pattern by sex and age in South Korea. In particular, severely obese young women had a substantial risk of suicidal behaviour. Our study results highlighted the importance of obesity management in the prevention of suicide among young women, and may be helpful for the drafting of the health agenda in Asian countries with an obesity prevalence and culture similar to those in Korea. PMID- 27256085 TI - Modelling estimates of the burden of respiratory syncytial virus infection in children in the UK. AB - OBJECTIVE: The burden of respiratory syncytial virus (RSV) illness is not well characterised in primary care. We estimated the burden of disease attributable to RSV in children in the UK between 1995 and 2009. DESIGN: Time-series regression modelling. SETTING: A multiple linear regression model based on weekly viral surveillance (RSV and influenza, Public Health England), and controlled for non specific seasonal drivers of disease, estimated the proportion of general practitioner (GP) episodes of care (counted as first visit in a series within 28 days; Clinical Practice Research Datalink, CPRD), hospitalisations (Hospital Episode Statistics, HES) and deaths (Office of National Statistics, ONS) attributable to RSV each season. PARTICIPANTS: Children 0-17 years registered with a GP in CPRD, or with a respiratory disease outcome in the HES or ONS databases. PRIMARY OUTCOME MEASURES: RSV-attributable burden of GP episodes, hospitalisations and deaths due to respiratory disease by age. RSV-attributable burden associated with selected antibiotic prescriptions. RESULTS: RSV attributable respiratory disease in the UK resulted in an estimated 450 158 GP episodes, 29 160 hospitalisations and 83 deaths per average season in children and adolescents, with the highest proportions in children <6 months of age (14 441/100 000 population, 4184/100 000 and 6/100 000, respectively). In an average season, there were an estimated 125 478 GP episodes for otitis media and 416 133 prescriptions for antibiotics attributable to RSV. More GP episodes, hospitalisations and deaths from respiratory disease were attributable to RSV than to influenza in children under 5 years. CONCLUSIONS: The burden of RSV in children in the UK exceeds that of influenza. RSV in children and adolescents contributes substantially to GP office visits for a diverse range of illnesses, and was associated with an average 416 133 prescribed antibiotic courses per season. Effective antiviral treatments and preventive vaccines are urgently needed for the management of RSV infection in children. TRIAL REGISTRATION NUMBER: NCT01706302. PMID- 27256087 TI - Establishing the effectiveness, cost-effectiveness and student experience of a Simulation-based education Training program On the Prevention of Falls (STOP Falls) among hospitalised inpatients: a protocol for a randomised controlled trial. AB - INTRODUCTION: Simulation-based education (SBE) is now commonly used across health professional disciplines to teach a range of skills. The evidence base supporting the effectiveness of this approach for improving patient health outcomes is relatively narrow, focused mainly on the development of procedural skills. However, there are other simulation approaches used to support non-procedure specific skills that are in need of further investigation. This cluster, cross over randomised controlled trial with a concurrent economic evaluation (cost per fall prevented) trial will evaluate the effectiveness, cost-effectiveness and student experience of health professional students undertaking simulation training for the prevention of falls among hospitalised inpatients. This research will target the students within the established undergraduate student placements of Monash University medicine, nursing and allied health across Peninsula Health acute and subacute inpatient wards. METHODS AND ANALYSIS: The intervention will train the students in how to provide the Safe Recovery program, the only single intervention approach demonstrated to reduce falls in hospitals. This will involve redevelopment of the Safe Recovery program into a one-to-many participant SBE program, so that groups of students learn the communication skills and falls prevention knowledge necessary for delivery of the program. The primary outcome of this research will be patient falls across participating inpatient wards, with secondary outcomes including student satisfaction with the SBE and knowledge gain, ward-level practice change and cost of acute/rehabilitation care for each patient measured using clinical costing data. ETHICS AND DISSEMINATION: The Human Research Ethics Committees of Peninsula Health (LRR/15/PH/11) and Monash University (CF15/3523-2015001384) have approved this research. The participant information and consent forms provide information on privacy, storage of results and dissemination. Registration of this trial has been completed with the Australian and New Zealand Clinical Trials Registry: ACTRN12615000817549. This study protocol has been prepared according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. TRIAL REGISTRATION NUMBER: ACTRN12615000817549; Pre-results. PMID- 27256088 TI - Risk factors of direct heat-related hospital admissions during the 2009 heatwave in Adelaide, Australia: a matched case-control study. AB - OBJECTIVE: The extreme heatwave of 2009 in South Australia dramatically increased morbidity, with a 14-fold increase in direct heat-related hospitalisation in metropolitan Adelaide. Our study aimed to identify risk factors for the excess morbidity. DESIGN: A matched case-control study of risk factors was conducted. SETTING: Patients and matched community controls were interviewed to gather data on demographics, living environment, social support, health status and behaviour changes during the heatwave. PARTICIPANTS: Cases were all hospital admissions with heat-related diagnoses during the 5-day heatwave in 2009. Controls were randomly selected from communities. OUTCOME MEASURES: Descriptive analyses, simple and multiple conditional logistic regressions were performed. Adjusted ORs (AORs) were estimated. RESULTS: In total, 143 hospital patients and 143 matched community controls were interviewed, with a mean age of 73 years (SD 21), 96% European ethnicity, 63% retired, 36% with high school or higher education, and 8% institutional living. The regression model indicated that compared with the controls, cases were more likely to have heart disease (AOR=13.56, 95% CI 1.27 to 144.86) and dementia (AOR=26.43, 95% CI 1.99 to 350.73). The protective factors included higher education level (AOR=0.48, 95% CI 0.23 to 0.99), having air conditioner in the bedroom (AOR=0.12, 95% CI 0.02 to 0.74), having an emergency button (AOR=0.09, 95% CI 0.01 to 0.96), using refreshment (AOR=0.10, 95% CI 0.01 to 0.84), and having more social activities (AOR=0.11, 95% CI 0.02 to 0.57). CONCLUSIONS: Pre-existing heart disease and dementia significantly increase the risk of direct heat-related hospitalisations during heatwaves. The presence of an air-conditioner in the bedroom, more social activities, a higher education level, use of emergency buttons and refreshments reduce the risk during heatwaves. PMID- 27256089 TI - Retrospective angiographic study to determine the effect of atherosclerotic stenoses of upstream arteries on the degree of atherosclerosis in distal vascular territories. AB - OBJECTIVE: Experimental coarctation of the aorta prevents the development of downstream atherosclerosis. The aim of this study was to find out whether or not atherosclerotic stenoses protect distal vascular territories from developing atherosclerosis in humans. DESIGN AND SETTING: A total of 2125 vascular segments from angiographies of 101 patients were evaluated by calculating the maximum degree of stenosis (NASCET criteria), the degree of calcification, the degree of collaterals and the Friesinger score. RESULTS: Stenosis >=30-49% was found in 685 vascular segments (32.2%), >=50-69% in 490 (23.1%), >=70-89% in 373 (17.6%) and >=90% in 265 (12.5%). If a stenosis of at least >=70-89% was present in the common iliac, the external iliac or the common femoral artery, the degrees of stenosis distal to it were lower than those on the contralateral side (19.8+/ 22.3% (CI 11.7 to 28.0) vs 25.2+/-20.7% (CI 21.2 to 29.1); Friesinger scores 1.1+/-1.2 (CI 0.6 to 1.5) vs 1.4+/-1.1 (CI 1.2 to 1.6); degrees of calcification 0.8+/-1.0 (CI 0.4 to 1.1) vs 1.2+/-1.1 (CI 1.2 to 1.6); p<0.05 each). This effect depended on the degree of proximal stenosis, but not on collaterals, and was most pronounced distal to stenoses of the common iliac, the superficial femoral and the popliteal artery. In regression models, stenoses of the pelvic arteries were shown to be an independent protective factor for the distal vascular territories. CONCLUSIONS: Atherosclerotic stenoses seem to protect distal vascular territories from developing atherosclerosis. The underlying pathophysiological mechanism of this phenomenon remains to be determined. It could be based on pulse pressure reduction. PMID- 27256090 TI - Risk factors for dermatitis in submariners during a submerged patrol: an observational cohort study. AB - OBJECTIVE: The aim of this pilot study was to determine risk factors, including Staphylococcus aureus nasal carriage, for dermatitis in submariners during a submarine patrol. PARTICIPANTS AND METHODS: 36 submariners undertaking a submerged 6-week patrol participated in the study. Severity of dermatitis and its impact was assessed using visual analogue scales and questionnaires at baseline and weekly throughout the patrol. S. aureus carriage levels in submariners were determined by nasal swabbing at baseline and shortly before disembarking the submarine. Occurrence of any skin or soft tissue infections (SSTI) were reported to the medical officer and swabs of the area were taken for subsequent analysis. RESULTS: S. aureus carriers were significantly more likely than non-carriers to have previously received treatment for a cutaneous abscess (39% vs 5%, OR=13 (95% CI 1.3 to 130)) with a trend to being submariners longer (p=0.051). Skin scores at baseline and on patrol were not significantly associated with carriage status. Higher dermatitis scores were observed in those who had been submariners longer (p=0.045). Smoking and allergies were not found to be linked to carriage status or skin health score in this cohort. CONCLUSIONS: This small pilot study investigates S. aureus carriage status and skin health in submariners. Length of submarine service but not S. aureus carriage was identified as a risk factor for worsening skin health in this small cohort during a 6-week patrol. This does not support S. aureus decolonisation to improve skin health in this population. Further investigation into causes of dermatitis in submariners is required. This data supports a better understanding of the potential impact of exposure to environmental factors that could affect skin health in submariners. PMID- 27256092 TI - Methamphetamine use in Central Germany: protocol for a qualitative study exploring requirements and challenges in healthcare from the professionals' perspective. AB - INTRODUCTION: The synthetic drug methamphetamine with its high addiction potential is associated with substantial adverse health effects. In Germany, especially Central Germany, the increase in the consumption of methamphetamine has exceeded that of other illegal drugs. The treatment system and service providers are facing new challenges due to this rise in consumption. This qualitative study will explore the demand created by the increasing healthcare needs of methamphetamine-addicted persons in Central Germany, and the difficulty of rehabilitating addicted people. METHODS AND ANALYSIS: The collection of empirical data will take place in a consecutive, two-stage process. In the first part of data collection, the experiences and perspectives of 40 professionals from numerous healthcare sectors for methamphetamine-addicted persons will be explored with the help of semistructured face-to-face interviews and probed by the research team. These findings will be discussed in 2 focus groups consisting of the participants of the face-to-face interviews; these group discussions comprise the second part of the data collection process. The interviews will be audio recorded, transcribed, and then subjected to qualitative content analysis. ETHICS AND DISSEMINATION: All interviewees will receive comprehensive written information about the study, and sign a declaration of consent prior to the interview. The study will comply rigorously with data protection legislation. The research team has obtained the approval of the Ethical Review Committee at the Martin Luther University Halle-Wittenberg, Germany. The results of the study will be published in high-quality, peer-reviewed international journals, presented at several congresses and used to design follow-up research projects. TRIAL REGISTRATION NUMBER: VfD_METH_MD_15_003600. PMID- 27256091 TI - How do women trade-off benefits and risks in chemotherapy treatment decisions based on gene expression profiling for early-stage breast cancer? A discrete choice experiment. AB - OBJECTIVES: Gene expression profiling (GEP) of tumours informs baseline risk prediction, potentially affecting adjuvant chemotherapy decisions for women with early-stage breast cancer. Since only 15% will experience a recurrence, concerns have been raised about potential harms from overtreatment and high GEP costs in publicly funded healthcare systems. We aimed to estimate preferences and personal utility of GEP testing information and benefit-risk trade-offs in chemotherapy treatment decisions. DESIGN, SETTING AND INTERVENTION: Based on literature review and findings from our qualitative research (focus groups, interviews with patients with breast cancer and medical oncologists), we developed a discrete choice experiment (DCE) survey and administered it via an internet panel. The DCE included 12 choice tasks with 5 attributes and 3 alternatives considering orthogonality, D-efficiency and level balance. PARTICIPANTS: The DCE survey was administered to 1004 Canadian women from the general population. MAIN OUTCOME MEASURES: Preferences were analysed using conditional logit and hierarchical Bayes and evaluated for goodness of fit. We conducted simulation analyses for alternative scenarios. RESULTS: GEP test score indicating likely benefit from chemotherapy was the most important attribute. Doctor's clinical estimate of the risk of cancer returning, trust in your cancer doctor and side effects of chemotherapy (temporary and permanent) were relatively less important but showed significant differences among levels. In the scenario analyses, 78% were likely to choose chemotherapy in a high-risk scenario, 55% in a moderate-risk scenario and 33% in a low-risk scenario, with the other attributes held constant. A high GEP score was more important in influencing the choice of chemotherapy for those at intermediate clinical risk. CONCLUSIONS: GEP testing information influences chemotherapy treatment decisions in early-stage breast cancer and varies depending on clinical risk. Clinicians should be aware of these differences and tailor the use of GEP testing accordingly. PMID- 27256093 TI - Protocol of a randomised phase III clinical trial of sequential capecitabine or 5 fluorouracil plus bevacizumab (Cape/5-FU-Bmab) to capecitabine or 5-fluorouracil plus oxaliplatin plus bevacizumab (CapeOX/mFOLFOX6-Bmab) versus combination CapeOX/mFOLFOX6-Bmab in advanced colorectal cancer: the C-cubed (C3) study. AB - INTRODUCTION: Results from several randomised trials suggest that the sequential use of cytotoxic agents in patients with metastatic colorectal cancer (mCRC) has the potential to improve overall survival compared with combination chemotherapy. This study is designed to investigate whether sequential treatment with bevacizumab-based first-line treatment with oxaliplatin is superior to combination treatment of mCRC. METHODS AND ANALYSIS: The C-cubed (C(3)) study is a two-arm, multicentre, open-label, randomised phase III trial in Japan comparing the efficacy and safety of sequential capecitabine or 5-fluorouracil plus bevacizumab (Cape/5-FU-Bmab) with escalation to capecitabine or 5-fluorouracil plus oxaliplatin plus bevacizumab (CapeOX/mFOLFOX6-Bmab) versus combination CapeOX/mFOLFOX6-Bmab as the first-line treatment of mCRC. In the sequential arm (Arm A: oxaliplatin 'wait-and-go'), treatment escalation from Cape/5-FU-Bmab to CapeOX/mFOLFOX6-Bmab is recommended in the case of progressive disease. In the combination arm (Arm B: oxaliplatin 'stop-and-go'), de-escalation from CapeOX/mFOLFOX6-Bmab to Cape/5-FU-Bmab is possible after 12 weeks of treatment. Re-escalation to CapeOX/mFOLFOX6-Bmab after progressive disease is considered only for patients who received de-escalation of oxaliplatin after 12 weeks of treatment not caused by oxaliplatin-associated toxicity. A target sample size of 304 evaluable patients is considered sufficient to validate an expected HR for time to failure of strategy of the sequential approach 'wait-and-go' compared to the combination approach 'stop-and go' with 80% power and 2-sided 5% alpha in case of a true HR<0.69. ETHICS AND DISSEMINATION: This study is conducted according to the standards of Good Clinical Practice and in compliance with the Declaration of Helsinki 2013 and local regulations, and has been submitted and approved by the Ethical Committee of the Non-Profit Organization MINS Institutional Review Board. The protocol and the trial results, even inconclusive, will be presented at international oncology congresses and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000015405, Pre-results. PMID- 27256095 TI - Clinical excellence: evidence on the assessment of senior doctors' applications to the UK Advisory Committee on Clinical Excellence Awards. Analysis of complete national data set. AB - OBJECTIVES: To inform the rational deployment of assessor resource in the evaluation of applications to the UK Advisory Committee on Clinical Excellence Awards (ACCEA). SETTING: ACCEA are responsible for a scheme to financially reward senior doctors in England and Wales who are assessed to be working over and above the standard expected of their role. PARTICIPANTS: Anonymised applications of consultants and senior academic GPs for awards were considered by members of 14 regional subcommittees and 2 national assessing committees during the 2014-2015 round of applications. DESIGN: It involved secondary analysis of complete anonymised national data set. PRIMARY AND SECONDARY OUTCOME MEASURES: We analysed scores for each of 1916 applications for a clinical excellence award across 4 levels of award. Scores were provided by members of 16 subcommittees. We assessed the reliability of assessments and described the variance in the assessment of scores. RESULTS: Members of regional subcommittees assessed 1529 new applications and 387 renewal applications. Average scores increased with the level of application being made. On average, applications were assessed by 9.5 assessors. The highest contributions to the variance in individual assessors' assessments of applications were attributable to assessors or to residual variance. The applicant accounted for around a quarter of the variance in scores for new bronze applications, with this proportion decreasing for higher award levels. Reliability in excess of 0.7 can be attained where 4 assessors score bronze applications, with twice as many assessors being required for higher levels of application. CONCLUSIONS: Assessment processes pertaining in the competitive allocation of public funds need to be credible and efficient. The present arrangements for assessing and scoring applications are defensible, depending on the level of reliability judged to be required in the assessment process. Some relatively minor reconfiguration in approaches to scoring might usefully be considered in future rounds of assessment. PMID- 27256094 TI - Community-based physical activity and nutrition programme for adults with metabolic syndrome in Vietnam: study protocol for a cluster-randomised controlled trial. AB - INTRODUCTION: Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases and type II diabetes. In Vietnam, more than one-quarter of its population aged 50-65 have MetS. This cluster-randomised controlled trial aims to evaluate the effectiveness of interventions to increase levels of physical activity and improve dietary behaviours among Vietnamese adults aged 50 65 years with MetS. METHOD AND ANALYSIS: This 6-month community-based intervention includes a range of strategies to improve physical activity and nutrition for adults with MetS in Hanam, a province located in northern Vietnam. 600 participants will be recruited from 6 communes with 100 participants per commune. The 6 selected communes will be randomly allocated to either an intervention group (m=3; n=300) or a control group (m=3; n=300). The intervention comprises booklets, education sessions, resistance bands and attending local walking groups that provide information and encourage participants to improve their physical activity and healthy eating behaviours during the 6-month period. The control group participants will receive standard and 1-time advice. Social cognitive theory is the theoretical concept underpinning this study. Measurements will be taken at baseline and postintervention to evaluate programme effectiveness. ETHICS AND DISSEMINATION: The research protocol was approved by the Curtin University Human Research Ethics Committee (approval number: HR139/2014). The results of the study will be disseminated through publications, reports and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12614000811606. PMID- 27256096 TI - Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression. AB - BACKGROUND: To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. METHODS: Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. RESULTS: Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. CONCLUSION: The clinical course of varicella and herpes zoster in children under immunosuppression is variable, with 4 (18 %) of 22 children showing a complicated course. Thorough assessment of VZV disease and vaccination history and correct VZV vaccination according to national guidelines at diagnosis of a rheumatic autoimmune disease is essential to minimize VZV complications during a later immunosuppressive treatment. PMID- 27256097 TI - Comparing Clinicopathologic and Radiographic Findings Between TT-UMP, Classical, and Non-Encapsulated Follicular Variants of Papillary Thyroid Carcinomas. AB - Thyroid tumors of uncertain malignant potential (TT-UMP) comprise an accepted subgroup of follicular-patterned thyroid tumors for which benignancy or malignancy cannot be precisely assessed. We aimed to evaluate the demographic characteristics, ultrasound (US) findings, and cytological results of patients with TT-UMP and compare these findings to a classical variant of papillary thyroid carcinoma (CV-PTC) and non-encapsulated follicular variant of PTC (NEFV PTC) patients; we also evaluated the immunohistochemical characteristics of patients with TT-UMP. Twenty-four patients with TT-UMP, 672 with CV-PTC, and 132 with NEFV-PTC were included in the study. Mean longitudinal nodule size and median nodule volume were higher in the TT-UMP group than in the CV-PTC and NEFV PTC groups (p < 0.001 and p < 0.001 for CV-PTC; p < 0.001 and p = 0.008 for NEFV PTC). The presence of halo and peripheral vascularization was observed more frequently in the TT-UMP group than in the CV-PTC group (p = 0.002 and p = 0.024). Benign and follicular neoplasm/suspicious for follicular neoplasm cytological results were higher in the TT-UMP group than in the CV-PTC group (p = 0.030 and p = 0.001). US findings were similar between TT-UMP and NEFV-PTC groups (all, p > 0.05). However, none of the patients with TT-UMP were called malignant; 105 patients (31.2 %) of CV-PTC and 11 patients (9.5 %) of NEFV-PTC (infiltrative FV) were classified as malignant cytologically. Tumor size was higher in the TT UMP group than in the CV-PTC and NEFV-PTC groups (p < 0.001 and p = 0.006). In the TT-UMP group, positive expression of HBME-1, CK-19, and Gal-3 was found in 50, 33.3, and 25 % of patients, respectively. This study demonstrated that none of the TT-UMP patients were evaluated as malignant in preoperative cytology. However, patients with TT-UMP had higher nodule and tumor sizes than CV-PTC and NEFV-PTC patients; US features were similar between NEFV-PTC and TT-UMP patients. PMID- 27256098 TI - Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin. AB - Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki 67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy. PMID- 27256099 TI - Assessment of cancer pain in a patient with communication difficulties: a case report. AB - BACKGROUND: The number of patients who have difficulty with mutual understanding has been increasing recently due to an aging society. This emerging issue needs to be addressed. We report an instructive case of a patient who had communication difficulties due to dementia and sequelae of alcoholic encephalopathy. CASE PRESENTATION: A 66-year-old man of Mongolian race presented with coronary arteriosclerosis, spinal canal stenosis, transverse colon cancer, and alcoholic encephalopathy. We had been requested to remove wires that had been used for the closure of his chest in a coronary artery bypass grafting procedure. However, on admission, a tortured expression and abdominal distention were observed, along with emaciation. We diagnosed terminal stage cancer, and palliative care was offered. An abdominal computed tomographic scan revealed rectal cancer with stenosis and invasion to the adjacent tissues. A metallic stent was inserted, leading to reduction of the abdominal distention and an improvement of tachycardia. However, the patient's tortured expression was not completely relieved; therefore, an assessment of cancer pain was considered. The Abbey Pain Scale was applied. On the basis of the patient's score, analgesics and an opioid, among other medications, were administered. These led to relief of the patient's tortured expression and reduced his Abbey Pain Scale score. Following this, the patient's vital signs continued to be stable, and he was transferred to the referral institution. CONCLUSIONS: Management of cancer pain in elderly patients with mutual understanding difficulties must be performed carefully. In the case of our patient, staff at the referral institution informed us of the patient's latent torture, and we applied the Abbey Pain Scale. There was some confusion and uncertainty regarding clinical management throughout the patient's care; however, his condition eventually stabilized. We believe the application of the Abbey Pain Scale assists in the relief of cancer pain. However, accumulation of further cases and experiences to verify this assessment is required. PMID- 27256100 TI - [Novel anti-osteoporotic drugs on the horizon]. AB - In recent years the great progress in knowledge on bone cell biology has allowed identification of molecular structures that can be targeted with pinpoint precision (druggable targets). Osteoclasts are regulated via the RANK-RANK-ligand (RANKL) signaling pathway and osteoblasts via the Wnt signaling pathway, both of which can be influenced for therapeutic measures. As a result the number of (functional) osteoclasts can be decreased or the genesis of osteoblasts can be increased and bone resorption is inhibited or bone formation is enhanced, respectively. Osteoclasts degrade collagen through cathepsin K and inactivation of this enzyme stabilizes the bone matrix; however, as osteoclasts are still able to maintain a stimulatory cross-talk with osteoblasts, formation of new bone will not be reduced. Parathyroid hormone-related protein plays a role in endochondral ossification and a synthetic analogue of this protein may have potent bone anabolic activity; however, the use of such new and highly efficient therapeutic principles comes with new questions and uncertainties on the sequence of therapies, duration of therapy, long-term side effects, undesired activation of metabolic pathways and effectiveness in comparison to other strategies of fracture prevention. PMID- 27256101 TI - Regarding "Radioembolization: Is Prophylactic Embolization of Hepaticoenteric Arteries Necessary? A Systematic Review". PMID- 27256102 TI - Irreversible Electroporation of Prostate Cancer: Patient-Specific Pretreatment Simulation by Electric Field Measurement in a 3D Bioprinted Textured Prostate Cancer Model to Achieve Optimal Electroporation Parameters for Image-Guided Focal Ablation. PMID- 27256103 TI - Cryoablation of Hepatocellular Carcinoma with High-Risk for Percutaneous Ablation: Safety and Efficacy. AB - PURPOSE: The aim of this study was to evaluate the safety and effectiveness of cryoablation in the treatment of subcapsular hepatocellular carcinoma (HCC) adjacent to various organs. MATERIALS AND METHODS: Twenty-eight patients with subcapsular HCC were treated with cryoablation in our institution. The degree of peri-procedural pain was measured using the visual analog scale (VAS). Technical success, local tumor progression, and overall disease progression rates were calculated. Procedure-related complications were identified by reviewing electronic medical records. Biochemical data, including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels before and after the procedure were collected. RESULTS: Subcapsular HCC tumors were located near the gallbladder, colon, stomach, kidney, diaphragm, or abdominal wall. The technical success rate of cryoablation was 96.4 % (27/28). Local recurrence- and progression-free survival rates were 96 and 84 % at 6 months, and 82 and 43 % at 1 year, respectively. All patients survived during the follow-up period. The VAS pain score ranged from 0 to 3 (mean, 1.57). A major complication occurred in one patient (3.6 %) and minor complications occurred at a rate of 17.9 %. Transient elevations of serum AST, ALT, and bilirubin levels were observed. CONCLUSION: Cryoablation is a safe and an effective procedure for the treatment of subcapsular HCC adjacent to various major organs. PMID- 27256104 TI - Percutaneous Image-Guided Screw Fixation of Bone Lesions in Cancer Patients: Double-Centre Analysis of Outcomes including Local Evolution of the Treated Focus. AB - AIM: To review outcomes and local evolution of treated lesions following percutaneous image-guided screw fixation (PIGSF) of pathological/insufficiency fractures (PF/InF) and impeding fractures (ImF) in cancer patients at two tertiary centres. MATERIALS AND METHODS: Thirty-two consecutive patients (mean age 67.5 years; range 33-86 years) with a range of tumours and prognoses underwent PIGSF for non/minimally displaced PF/InF and ImF. Screws were placed under CT/fluoroscopy or cone-beam CT guidance, with or without cementoplasty. Clinical outcomes were assessed using a simple 4-point scale (1 = worse; 2 = stable; 3 = improved; 4 = significantly improved). Local evolution was reviewed on most recent follow-up imaging. Technical success, complications, and overall survival were evaluated. RESULTS: Thirty-six lesions were treated with 74 screws mainly in the pelvis and femoral neck (58.2 %); including 47.2 % PF, 13.9 % InF, and 38.9 % ImF. Cementoplasty was performed in 63.9 % of the cases. Technical success was 91.6 %. Hospital stay was <=3 days; 87.1 % of lesions were improved at 1-month follow-up; three major complications (early screw-impingement radiculopathy; accelerated coxarthrosis; late coxofemoral septic arthritis) and one minor complication were observed. Unfavourable local evolution at imaging occurred in 3/24 lesions (12.5 %) at mean 8.7-month follow-up, including poor consolidation (one case) and screw loosening (two cases, at least 1 symptomatic). There were no cases of secondary fractures. CONCLUSIONS: PIGSF is feasible for a wide range of oncologic patients, offering good short-term efficacy, acceptable complication rates, and rapid recovery. Unfavourable local evolution at imaging may be relatively frequent, and requires close clinico-radiological surveillance. PMID- 27256105 TI - Ablation of Adenosine Monophosphate-Activated Protein Kinase alpha1 in Vascular Smooth Muscle Cells Promotes Diet-Induced Atherosclerotic Calcification In Vivo. AB - RATIONALE: Atherosclerotic calcification is highly linked with plaque rapture. How calcification is regulated is poorly characterized. OBJECTIVE: We sought to determine the contributions of AMP-activated protein kinase (AMPK) in atherosclerotic calcification. METHODS AND RESULTS: Aortic calcification was evaluated in aortic roots and brachiocephalic arteries of atherosclerotic prone ApoE(-/-) mice or in mice with dual deficiencies of ApoE and AMPKalpha isoforms in whole body (ApoE(-/-)/AMPKalpha1(-/-) and ApoE(-/-)/AMPKalpha2(-/-)) or vascular smooth muscle cell (VSMC)-specific or macrophage-specific knockout of AMPKalpha1 fed with Western diet for 24 weeks. Genetic deficiency of AMPKalpha1 but not of AMPKalpha2 promoted atherosclerotic calcification and the expression of Runx2 (Runt-related transcription factor). Conversely, chronic administration of metformin, which activated AMPK, markedly reduced atherosclerotic calcification and Runx2 expression in ApoE(-/-) mice but had less effects in ApoE(-/-)/AMPKalpha1(-/-) mice. Furthermore, VSMC-specific but not macrophage specific ablation of AMPKalpha1 promoted aortic calcification in vivo. Ablation of AMPKalpha1 in VSMC prevented Runx2 from proteasome degradation in parallel with aberrant osteoblastic differentiation of VSMC, whereas AMPK activation promoted Runx2 post-translational modification by small ubiquitin-like modifier (SUMO, SUMOylation), which is associated with its instability. Mechanically, we found that AMPKalpha1 directly phosphorylated protein inhibitor of activated STAT 1 (PIAS1), the SUMO E3-ligase of Runx2, at serine 510, to promote its SUMO E3 ligase activity. Finally, mutation of protein inhibitor of activated STAT-1 at serine 510 suppressed metformin-induced Runx2 SUMOylation and subsequently prevented metformin's effect on reducing oxidized low-density lipoprotein triggered Runx2 expression in VSMC. CONCLUSIONS: AMPKalpha1 phosphorylated protein inhibitor of activated STAT-1 to promote Runx2 SUMOylation and subsequently lead to its instability. AMPKalpha1 deficiency in VSMC increased Runx2 expression and promoted atherosclerotic calcification in vivo. PMID- 27256106 TI - Enumeration and Molecular Characterisation of Circulating Tumour Cells in Endometrial Cancer. AB - BACKGROUND: This is a feasibility study to determine whether circulating tumour cells (CTCs) are detectable and suitable for molecular profiling in advanced endometrial cancer (aEC). METHOD: Between October 2012 and February 2014, 30 patients with aEC had baseline and up to 3 follow-up samples. CTCs and stathmin expression were evaluated using the CellSearch platform. Epithelial cell adhesion molecule (EpCAM) and stathmin immunohistochemistry were performed on FFPE tumour tissue. RESULTS: Eighteen from 30 (60%) patients had detectable CTCs during study [1 CTC (n = 7), 2 (n = 4), 3 (n = 1), 4 (n = 2), 7 (n = 1), 8 (n = 1), 22 (n = 1), 172 (n = 1) in 7.5 ml blood]. Ten from 18 patients had between 50 and 100% of detectable CTCs that were stathmin positive. More CTC-positive than CTC-negative patients had non-endometrioid versus endometrioid histology, tumour size >=5 versus <5 cm, higher-stage disease and worse survival [hazard ratio 3.3, p > 0.05, 95% confidence interval 0.7-16.2]. Twenty-one tumour blocks were tested for EpCAM and stathmin immunohistochemistry (IHC). Stathmin tumour immunostaining scores (TIS) on IHC were higher in CTC-positive patients. CONCLUSION: CTC enumeration and molecular profiling with stathmin on the CellSearch platform is feasible in aEC. Stathmin TIS on IHC, a known prognostic marker in EC, was associated with CTC positivity. PMID- 27256107 TI - Clinical Presentation and Diagnostic Challenges of Thyroid Lymphoma: A Cohort Study. AB - BACKGROUND: Thyroid lymphoma is a relatively rare disease often posing a diagnostic challenge. Reaching the final diagnosis can be delayed if insufficient biopsy material is obtained for immunohistochemistry analysis. The aim of this study was to evaluate the clinical, biochemical, and radiological features of thyroid lymphoma. METHODS: A retrospective analysis was conducted of all Mayo Clinic patients evaluated between 2000 and 2014 who had a tissue biopsy positive for thyroid lymphoma. RESULTS: Seventy-five subjects had biopsy-proven thyroid lymphoma, and 62.7% were primary thyroid lymphomas. The median age at diagnosis was 67 years (range 20-90 years). A total of 50.7% were male, and 54.7% had a history of Hashimoto's thyroiditis. Presenting symptoms included neck mass (88%), dysphagia (45.3%), and hoarseness (37.3%). The typical ultrasound appearance consisted of a solid, hypoechoic mass with increased vascularity and variable edge characteristics. Fine-needle aspiration (FNA) biopsies were abnormal in 70.7% of cases, and 42% indicated a specific lymphoma subtype. The diagnosis was confirmed in 53.3% by core biopsy, in 21.3% by thyroidectomy (partial or total), in 12% through incisional biopsy, and in 12% by lymph node biopsy. Core biopsy had a higher sensitivity compared with FNA (93% vs. 71%, p = 0.006). CONCLUSION: A rapidly enlarging neck mass in the setting of Hashimoto's thyroiditis should raise suspicion for thyroid lymphoma. Radiologically, this usually presents as a large, unilateral, thyroid-centered mass, hypoechoic by ultrasound, and expanding into adjacent soft tissues. Core-needle biopsy should be the first diagnostic test to expedite reaching the final diagnosis and decrease patient burden of additional tests and interventions. PMID- 27256108 TI - Simultaneous biopsy and radiofrequency ablation of T1a renal cell carcinoma. AB - OBJECTIVE: The goal of this study was to retrospectively evaluate the outcome, including feasibility, safety, diagnostic yield, and factors affecting the success of computed tomography fluoroscopy-guided biopsy when performed during the same procedure than radiofrequency ablation (RFA) in renal tumors strongly suspected of being T1a renal cell carcinoma (RCC). MATERIALS AND METHODS: Nineteen patients (13 men, 6 women; mean age, 66.7 years) with a total of 19 suspected renal tumors (mean diameter, 1.8cm) underwent computed tomography fluoroscopy-guided biopsy during (n=6) or immediately after (n=13) RFA. All patients were strongly suspected of having RCC on the basis of patient's medical histories and/or the results of imaging investigations. All procedures were divided into diagnostic and non-diagnostic biopsies. Various variables were compared between the 2 groups using univariate analysis. RESULTS: In all tumors, biopsy procedures were technically feasible. No major complications were observed, except for 8 minor post-procedural bleedings. All but one tumor was completely ablated. Local recurrence in the ablation zone as well as tumor seeding in retroperitoneal fat occurred in 1 patient 8.5months after the procedure and were successfully treated with further percutaneous cryoablation. Thirteen tumors were diagnosed as RCC, whereas 6 were ultimately found to contain normal renal tissue (n=5) or connective tissue (n=1). Univariate analysis revealed that none of the variables were significantly different between the diagnostic and non-diagnostic biopsies. CONCLUSION: The performance of renal tumor biopsy and RFA in the same session is feasible and safe. Although pre treatment pathological diagnosis would be generally desirable, simultaneous biopsy with RFA can be an option for the patients who are not amenable to pre treatment biopsy. PMID- 27256109 TI - Induction chemotherapy for head and neck squamous cell carcinoma. PMID- 27256110 TI - S-adenosylmethionine reduces airway inflammation and fibrosis in a murine model of chronic severe asthma via suppression of oxidative stress. AB - Increased oxidative stress has an important role in asthmatic airway inflammation and remodeling. A potent methyl donor, S-adenosylmethionine (SAMe), is known to protect against tissue injury and fibrosis through modulation of oxidative stress. The aim of this study was to evaluate the effect of SAMe on airway inflammation and remodeling in a murine model of chronic asthma. A mouse model was generated by repeated intranasal challenge with ovalbumin and Aspergillus fungal protease twice a week for 8 weeks. SAMe was orally administered every 24 h for 8 weeks. We performed bronchoalveolar lavage (BAL) fluid analysis and histopathological examination. The levels of various cytokines and 4-hydroxy-2 nonenal (HNE) were measured in the lung tissue. Cultured macrophages and fibroblasts were employed to evaluate the underlying anti-inflammatory and antifibrotic mechanisms of SAMe. The magnitude of airway inflammation and fibrosis, as well as the total BAL cell counts, were significantly suppressed in the SAMe-treated groups. A reduction in T helper type 2 pro-inflammatory cytokines and HNE levels was observed in mouse lung tissue after SAMe administration. Macrophages cultured with SAMe also showed reduced cellular oxidative stress and pro-inflammatory cytokine production. Moreover, SAMe treatment attenuated transforming growth factor-beta (TGF-beta)-induced fibronectin expression in cultured fibroblasts. SAMe had a suppressive effect on airway inflammation and fibrosis in a mouse model of chronic asthma, at least partially through the attenuation of oxidative stress and TGF-beta-induced fibronectin expression. The results of this study suggest a potential role for SAMe as a novel therapeutic agent in chronic asthma. PMID- 27256111 TI - Concurrent progress of reprogramming and gene correction to overcome therapeutic limitation of mutant ALK2-iPSC. AB - Fibrodysplasia ossificans progressiva (FOP) syndrome is caused by mutation of the gene ACVR1, encoding a constitutive active bone morphogenetic protein type I receptor (also called ALK2) to induce heterotopic ossification in the patient. To genetically correct it, we attempted to generate the mutant ALK2-iPSCs (mALK2 iPSCs) from FOP-human dermal fibroblasts. However, the mALK2 leads to inhibitory pluripotency maintenance, or impaired clonogenic potential after single-cell dissociation as an inevitable step, which applies gene-correction tools to induced pluripotent stem cells (iPSCs). Thus, current iPSC-based gene therapy approach reveals a limitation that is not readily applicable to iPSCs with ALK2 mutation. Here we developed a simplified one-step procedure by simultaneously introducing reprogramming and gene-editing components into human fibroblasts derived from patient with FOP syndrome, and genetically treated it. The mixtures of reprogramming and gene-editing components are composed of reprogramming episomal vectors, CRISPR/Cas9-expressing vectors and single-stranded oligodeoxynucleotide harboring normal base to correct ALK2 c.617G>A. The one-step mediated ALK2 gene-corrected iPSCs restored global gene expression pattern, as well as mineralization to the extent of normal iPSCs. This procedure not only helps save time, labor and costs but also opens up a new paradigm that is beyond the current application of gene-editing methodologies, which is hampered by inhibitory pluripotency-maintenance requirements, or vulnerability of single-cell dissociated iPSCs. PMID- 27256112 TI - Leucine in Obesity: Therapeutic Prospects. AB - Obesity develops from an imbalance of energy homeostasis and is associated with chronic low-grade inflammation in white adipose tissues (WAT). Inflammation is involved in the pathophysiology of many obesity-induced disorders including insulin resistance and diabetes. Increasing evidence has shown that dietary leucine supplementation positively affects the parameters associated with obesity and obesity-related metabolic disorders. The beneficial effects include increased loss of body weight, reduced WAT inflammation, improved lipid and glucose metabolism, enhanced mitochondrial function, and preserved lean body mass. Although these beneficial effects have not been clearly established, dietary leucine supplementation, either alone or as part of a therapeutic regimen, may be a good nutritional tool in the prevention and management of obesity and obesity induced metabolic disorders. PMID- 27256114 TI - Corrigendum to: Modulation of functional network with real-time fMRI feedback training of right premotor cortex activity [Neuropsychologia (2014) 111-123]. PMID- 27256113 TI - Glutamate Neurotransmission in Rodent Models of Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is a leading cause of death and disability in people younger than 45 and is a significant public health concern. In addition to primary mechanical damage to cells and tissue, TBI involves additional molecular mechanisms of injury, termed secondary injury, that continue to evolve over hours, days, weeks, and beyond. The trajectory of recovery after TBI is highly unpredictable and in many cases results in chronic cognitive and behavioral changes. Acutely after TBI, there is an unregulated release of glutamate that cannot be buffered or cleared effectively, resulting in damaging levels of glutamate in the extracellular space. This initial loss of glutamate homeostasis may initiate additional changes in glutamate regulation. The excitatory amino acid transporters (EAATs) are expressed on both neurons and glia and are the principal mechanism for maintaining extracellular glutamate levels. Diffusion of glutamate outside the synapse due to impaired uptake may lead to increased extrasynaptic glutamate signaling, secondary injury through activation of cell death pathways, and loss of fidelity and specificity of synaptic transmission. Coordination of glutamate release and uptake is critical to regulating synaptic strength, long-term potentiation and depression, and cognitive processes. In this review, we will discuss dysregulation of extracellular glutamate and glutamate uptake in the acute stage of TBI and how failure to resolve acute disruptions in glutamate homeostatic mechanisms may play a causal role in chronic cognitive symptoms after TBI. PMID- 27256115 TI - Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues. AB - Microsomal triglyceride transfer protein (MTP) is a unique lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins by the liver and intestine. Previous studies in mice identified a splice variant of MTP with an alternate first exon. Splice variants of human MTP have not been reported. Using PCR approaches we have identified two splice variants in human tissues, which we have named MTP-B and MTP-C. MTP-B has a unique first exon (Ex1B) located 10.5 kb upstream of the first exon (Ex1A) for canonical MTP (MTP-A); MTP-C contains both first exons for MTP-A and MTP-B. MTP-B was found in a number of tissues, whereas MTP-C was prominent in brain and testis. MTP-B does not encode a protein; MTP-C encodes the same protein encoded by MTP-A, although MTP-C translation is strongly inhibited by regulatory elements within its 5'-UTR. Using luciferase assays, we demonstrate that the promoter region upstream of exon 1B is quite adequate to drive expression of MTP. We conclude that alternate splicing plays a key role in regulating cellular MTP levels by introducing distinct promoter regions and unique 5'-UTRs, which contain elements that alter translation efficiency, enabling the cell to optimize MTP activity. PMID- 27256116 TI - Mitigation in the toxicity of graphene oxide nanosheets towards Escherichia coli in the presence of humic acid. AB - GO nanosheets have been reported to show strong cytotoxicity towards Escherichia coli (E. coli) in aqueous solution. Natural organic matters (NOMs) in water may probably coat on the surface of GO nanosheets, which possibly influence its cytotoxicity. In this study, we illustrated how humic acid (HA), a ubiquitous NOM, mitigated the toxicity of GO nanosheets towards E. coli based on the cytotoxicity mechanism of GO nanosheets. Adsorption and cell viability tests proved that HA was adsorbed by GO nanosheets and decreased the toxicity of GO nanosheets towards E. coli. It was found that HA was adsorbed on the surface of GO nanosheets by polar groups, which prevented E. coli from contacting with GO nanosheets and weakened the toxicity of GO nanosheets. Besides, HA exerted an antioxidant role in maintaining the activity of the antioxidant enzyme and decreasing the ROS generation according to the results of oxidative stress experiments. The work revealed that HA relieved the toxicity of GO nanosheets and decreased the ecological risks induced by GO nanosheets. PMID- 27256118 TI - Letter From The Editor. PMID- 27256117 TI - A novel suicide shuttle plasmid for Streptococcus suis serotype 2 and Streptococcus equi ssp. zooepidemicus gene mutation. AB - The mariner-based Himar1 system has been utilized for creating mutant libraries of many Gram-positive bacteria. Streptococcus suis serotype 2 (SS2) and Streptococcus equi ssp. zooepidemicus (SEZ) are primary pathogens of swine that threaten the swine industry in China. To provide a forward-genetics technology for finding virulent phenotype-related genes in these two pathogens, we constructed a novel temperature-sensitive suicide shuttle plasmid, pMar4s, which contains the Himar1 system transposon, TnYLB-1, and the Himar1 C9 transposase from pMarA and the repTAs temperature-sensitive fragment from pSET4s. The kanamycin (Kan) resistance gene was in the TnYLB-1 transposon. Temperature sensitivity and Kan resistance allowed the selection of mutant strains and construction of the mutant library. The SS2 and SEZ mutant libraries were successfully constructed using the pMar4s plasmid. Inverse-Polymerase Chain Reaction (Inverse-PCR) results revealed large variability in transposon insertion sites and that the library could be used for phenotype alteration screening. The thiamine biosynthesis gene apbE was screened for its influence on SS2 anti phagocytosis; likewise, the sagF gene was identified to be a hemolytic activity related gene in SEZ. pMar4s was suitable for mutant library construction, providing more information regarding SS2 and SEZ virulence factors and illustrating the pathogenesis of swine streptococcosis. PMID- 27256119 TI - Locating Biobanks in the Canadian Privacy Maze. AB - Although Canada has not yet enacted any biobanking-specific privacy law, guidance and oversight are provided via various federal and provincial health and privacy related laws as well as via ethics and policy documents. The primary policy document governing health research, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, provides the framework for the strong role of Research Ethics Boards in Canada, and limits research funding from Canada's three main federal funding agencies to those who agree to adhere to its policies. The broad consent model is gaining traction in Canada, although lack of legal and constitutional precedence for the broad consent or opt-out options makes this an evolving issue. In general, data is required to be coded; more specific security measures are outlined in guidelines that may be implemented by local policy. International sharing is allowed, and Canada meets the European Union's standards for receipt of data and samples. PMID- 27256120 TI - Biobanking in Estonia. AB - Estonia is a democratic, parliamentary republic with a health care system that is built on the principle of compulsory, solidarity-based insurance and the all round availability of services of private service providers. Estonia has specific biobank legislation as well as oversight via data protection laws. Its population based biobank, the Estonian Genome Center (EGCUT), established in 2001, is one of the largest biobanks in Europe, and its database may be used only for scientific research, public health research, and statistics. The EGCUT can issue data to a third party, but only in coded form. This comprehensive database of genotypic, phenotypic, health, and genealogical information represents about 5% of Estonia's adult population, and is the largest cohort ever gathered in Estonia. Government approval is required for international data sharing, and sharing can be further limited by the requirement of ethics approval and permission from Estonian government. PMID- 27256121 TI - Biobanks as a Central Part of the Finnish Growth and Genomic Strategies: How to Balance Privacy in an Innovation Ecosystem? AB - Finland has aimed to make itself an international leader in genomic research and related business and, in working towards that goal, has enacted biobank legislation. The Biobank Act requires biobanks to gain approval, be supervised, and register at the national level. Numerous other laws may also apply in any given research setting, such as the Personal Data Act, the Medical Research Act, and the Act on Medical Use of Human Organs and Tissues.In terms of privacy protection, anonymization is generally not permitted under Finnish law and therefore most biobanks pseudonomize data and samples. However, the broad understanding of what is identifiable data in Finland has created difficulties in sharing with non-EU countries. Furthermore, consent to biobank research is only applicable to the sample and related data, not to data stored in other health related registries, and consent is only to the field of research for that particular biobank. These restrictions impede the sharing of samples and data for research. PMID- 27256122 TI - Privacy Laws and Biobanking in Germany. AB - While the possibility of enacting a sui generis Biobank Act has been debated in Germany at great length, as of yet the country has not implemented any biobankspecific legislation. Instead, oversight is available via a network of research and privacy laws, including those of the European Union. The Nationale Kohorte, Germany's large-scale, population-based epidemiological research biobank, is funded by the Federal Ministry of Education and Research, and there are currently 108 registered bio-banks throughout Germany. The current system, including the structure and study design of the Nationale Kohorte, privileges the protection of personal information even at the cost of socially desirable research; it remains to be seen if forthcoming legislation will shift this balance. PMID- 27256123 TI - Biobanking and Privacy in India. AB - Biobank-based research is not specifically addressed in Indian statutory law and therefore Indian Council for Medical Research guidelines are the primary regulators of biobank research in India. The guidelines allow for broad consent and for any level of identification of specimens. Although privacy is a fundamental right under the Indian Constitution, courts have limited this right when it conflicts with other rights or with the public interest. Furthermore, there is no established privacy test or actionable privacy right in the common law of India. In order to facilitate biobank-based research, both of these lacunae should be addressed by statutory law specifically addressing biobanking and more directly addressing the accompanying privacy concerns. A biobank specific law should be written with international guidelines in mind, but harmonization with other laws should not be attempted until after India has created a law addressing biobank research within the unique legal and cultural environment of India. PMID- 27256124 TI - Mexican Regulation of Biobanks. AB - Biobank-based research in Mexico is mostly governed by research and data protection laws. There is no direct mention of biobanks in either statutory or regulatory law besides a requirement that the Federal Ministry of Health and a Mexican institution devoted to scientific research approve the transfer of biological materials outside of Mexico for population genetics research purposes. Such requirements are the basis of Genomic Sovereignty in Mexico, but such requirements have not prevented international collaboration. In addition, Mexican law singles out genetic research in informed consent provisions, but it does not specify whether all biobank-based research is genetic research. In order to facilitate international collaboration on biobank-based research, Mexico should directly address biobanking in its laws, building on the research framework and data protection framework already in place. PMID- 27256125 TI - Regulating Privacy and Biobanks in the Netherlands. AB - The Netherlands does not have any specific legislation pertaining to human biological materials and data collection by biobanks. Instead, these issues are governed by a patchwork of laws, codes of practices, and other ethical instruments, where special emphasis is given to the right to privacy and self determination. While draft legislation for biobanking was scheduled to enter into force in 2007, as of mid-2015 such legislation was still under consideration, with the intent that it would focus particularly on individual self determination, the interests of research, the use of bodily materials collected by biobanks for criminal law purposes, and dilemmas around results that are clinically relevant for biobank participants. Under the current framework, the amount of privacy protection afforded to data is linked to its level of identifiability. International sharing of personal data to non-EU/European Economic Area countries is allowed if these countries provide adequate protection. PMID- 27256126 TI - Biobank and Genomic Research in Uganda: Are Extant Privacy and Confidentiality Regimes Adequate? AB - Not many African countries have been able to develop a robust system for regulating health research within their respective jurisdictions, particularly in the realm of biobanking and genomics. This is not without reason. Aside from underdevelopment and all that it entails or perhaps in consequence thereof, countries in the region have been unable to make significant strides in medical research. But there are exceptions. Amongst the few seeming success stories is Uganda. Nonetheless, although the country has developed what appears to be a functional framework to govern genomic research and biobanking, the consistency of key provisions with international standards, especially those pertaining to privacy of research participants and confidentiality of their health information, is not at all clear. Yet, making this determination - the main objective of this article - is critical in determining the adequacy of protection available to human research subjects in the country. PMID- 27256127 TI - Biobank Report: United Kingdom. AB - The United Kingdom is a leader in genomics research, and the presence of numerous types of biobanks and the linking of health data and research within the UK evidences the importance of biobank-based research in the UK. There is no biobank specific law in the UK and research on biobank materials is governed by a confusing set of statutory law, common law, regulations, and guidance documents. Several layers of applicable law, from European to local, further complicate an understanding of privacy protections. Finally, biobanks frequently contain data in addition to the samples; the legal framework in the UK generally differentiates between data and samples and the form of the data affects the applicability of legal provisions. Biobanks must be licensed by the Human Tissue Authority; certain projects must be reviewed by Research Ethics Committees, and all projects are encouraged to be reviewed by them. Data Access Committees in biobanks are also common in the UK. While this confusing array of legal provisions leaves privacy protections in biobanking somewhat unclear, changes at the EU level may contribute to harmonization of approaches to privacy. PMID- 27256128 TI - Biobanking Research and Privacy Laws in the United States. AB - Privacy is protected in biobank-based research in the US primarily by the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule and the Federal Policy for Protection of Human Subjects (Common Rule). Neither rule, however, was created to function in the unique context of biobank research, and therefore neither applies to all biobank-based research. Not only is it challenging to determine when the HIPAA Privacy Rule or the Common Rule apply, but these laws apply different standards to protect privacy. In addition, many other federal and state laws may be applicable to a particular biobank, researcher, or project. US law also does not directly address international sharing of data or specimens outside of the EU-US Safe Harbor Agreement, which only applies to receipt of data by certain US entities from EU countries, and is in the process of revision. Although new rules would help clarify privacy protections in biobanking, any implemented changes should be studied to determine the sufficiency of the protections as well as its ability to facilitate or hinder international collaborations. PMID- 27256129 TI - EU Laws on Privacy in Genomic Databases and Biobanking. AB - Both the European Union and the Council of Europe have a bearing on privacy in genomic databases and biobanking. In terms of legislation, the processing of personal data as it relates to the right to privacy is currently largely regulated in Europe by Directive 95/46/EC, which requires that processing be "fair and lawful" and follow a set of principles, meaning that the data be processed only for stated purposes, be sufficient for the purposes of the processing, be kept only for so long as is necessary to achieve those purposes, and be kept securely and only in an identifiable state for such time as is necessary for the processing. The European privacy regime does not require the de identification (anonymization) of personal data used in genomic databases or biobanks, and alongside this practice informed consent as well as governance and oversight mechanisms provide for the protection of genomic data. PMID- 27256130 TI - The European Union's Adequacy Approach to Privacy and International Data Sharing in Health Research. AB - The European Union (EU) approach to data protection consists of assessing the adequacy of the data protection offered by the laws of a particular jurisdiction against a set of principles that includes purpose limitation, transparency, quality, proportionality, security, access, and rectification. The EU's Data Protection Directive sets conditions on the transfer of data to third countries by prohibiting Member States from transferring to such countries as have been deemed inadequate in terms of the data protection regimes. In theory, each jurisdiction is evaluated similarly and must be found fully compliant with the EU's data protection principles to be considered adequate. In practice, the inconsistency with which these evaluations are made presents a hurdle to international data-sharing and makes difficult the integration of different data sharing approaches; in the 20 years since the Directive was first adopted, the laws of only five countries from outside of the EU, Economic Area, or the European Free Trade Agreement have been deemed adequate to engage in data transfers without the need for further administrative safeguards. PMID- 27256131 TI - Privacy and Security within Biobanking: The Role of Information Technology. AB - Along with technical issues, biobanking frequently raises important privacy and security issues that must be resolved as biobanks continue to grow in scale and scope. Consent mechanisms currently in use range from fine-grained to very broad, and in some cases participants are offered very few privacy protections. However, developments in information technology are bringing improvements. New programs and systems are being developed to allow researchers to conduct analyses without distributing the data itself offsite, either by allowing the investigator to communicate with a central computer, or by having each site participate in meta analysis that results in a shared statistic or final significance result. The implementation of security protocols into the research biobanking setting requires three key elements: authentication, authorization, and auditing. Authentication is the process of making sure individuals are who they claim to be, frequently through the use of a password, a key fob, or a physical (i.e., retinal or fingerprint) scan. Authorization involves ensuring that every individual who attempts an action has permission to do that action. Finally, auditing allows for actions to be logged so that inappropriate or unethical actions can later be traced back to their source. PMID- 27256132 TI - Comparative Approaches to Biobanks and Privacy. AB - Laws in the 20 jurisdictions studied for this project display many similar approaches to protecting privacy in biobank research. Although few have enacted biobank-specific legislation, many countries address biobanking within other laws. All provide for some oversight mechanisms for biobank research, even though the nature of that oversight varies between jurisdictions. Most have some sort of controlled access system in place for research with biobank specimens. While broad consent models facilitate biobanking, countries without national or federated biobanks have been slow to adopt broad consent. International guidelines have facilitated sharing and generally take a proportional risk approach, but many countries have provisions guiding international sharing and a few even limit international sharing. Although privacy laws may not prohibit international collaborations, the multi-prong approach to privacy unique to each jurisdiction can complicate international sharing. These symposium issues can serve as a resource for explaining the sometimes intricate privacy laws in each studied jurisdiction, outlining the key issues with regards to privacy and biobanking, and serving to describe a framework for the process of harmonization of privacy laws. PMID- 27256133 TI - The Forced Marriage of Minors: A Neglected Form of Child Abuse. AB - The forced marriage of minors is child abuse, consequently duties exist to stop them. Yet over 14 million forced marriages of minors occur annually in developing countries. The American Bar Association (ABA) concludes that the problem in the US is significant, widespread but largely ignored, and that few US laws protect minors from forced marriages. Although their best chance of rescue often involves visits to health care providers, US providers show little awareness of this growing problem. Strategies discussed to stop forced marriages include recommendations from the UN, the ABA, and the UK. The author anticipates and responds to criticisms that first, no duty to intervene exists without better laws and practice guidelines; and second, that such marriages are not child abuse in traditions where parental rights or familism allegedly justify them. PMID- 27256134 TI - Whither the "Improvement Standard"? Coverage for Severe Brain Injury after Jimmo v. Sebelius. AB - As improvements in neuroscience have enabled a better understanding of disorders of consciousness as well as methods to treat them, a hurdle that has become all too prevalent is the denial of coverage for treatment and rehabilitation services. In 2011, a settlement emerged from a Vermont District Court case, Jimmo v. Sebelius, which was brought to stop the use of an "improvement standard" that required tangible progress over an identifiable period of time for Medicare coverage of services. While the use of this standard can have deleterious effects on those with many chronic conditions, it is especially burdensome for those in the minimally conscious state (MCS), where improvements are unpredictable and often not manifested through repeatable overt behaviors. Though the focus of this paper is on the challenges of brain injury and the minimally conscious state, which an estimated 100,000 to 200,000 individuals suffer from in the United States, the post-Jimmo arguments presented can and should have a broad impact as envisioned by the plaintiffs who brought the case on behalf of multiple advocacy groups representing patients with a range of chronic care conditions. PMID- 27256136 TI - Genomic Test Results and the Courtroom: The Roles of Experts and Expert Testimony. AB - The rapid advancement from single-gene testing to whole genome sequencing has significantly broadened the type and amount of information available to researchers, physicians, patients, and the public in general. Much debate has ensued about whether genomic test results should be reported to research participants, patients and consumers, and at what stage we can be sure that existing evidence justifies their use in clinical settings. Courts and judges evaluating the utility of these results will not be immune to this uncertainty. As scholars increasingly explore the duty of care standards related to reporting genomic test results, it is timely to provide a framework for understanding how uncertainty about genetic and genomic tests influences evidentiary considerations in the court room. Here, we explore the subtleties and nuances of interpreting genetic data in an environment of substantial discord related to the value that individuals should place on genetic and genomic tests. In conjunction, we discuss the roles courts should play in qualifying experts, expert testimony, and genetic and genomic tests given the intricate and complex nature of genetic and genomic information. PMID- 27256135 TI - Contrasting Medical and Legal Standards of Evidence: A Precision Medicine Case Study. AB - As the health care system transitions to a precision medicine approach that tailors clinical care to the genetic profile of the individual patient, there is a potential tension between the clinical uptake of new technologies by providers and the legal system's expectation of the standard of care in applying such technologies. We examine this tension by comparing the type of evidence that physicians and courts are likely to rely on in determining a duty to recommend pharmacogenetic testing of patients prescribed the oral anti-coagulant drug warfarin. There is a large body of inconsistent evidence and factors for and against such testing, but physicians and courts are likely to weigh this evidence differently. The potential implications for medical malpractice risk are evaluated and discussed. PMID- 27256137 TI - How Genetics Might Affect Real Property Rights: Currents in Contemporary Bioethics. AB - New developments in genetics could affect a variety of real property rights. Mortgage lenders, mortgage insurers, real estate sellers, senior living centers, retirement communities, or other parties in residential real estate transactions begin requiring predictive genetic information as part of the application process. One likely use would be by retirement communities to learn an individual's genetic risk for Alzheimer's disease. The federal Fair Housing Act prohibits discrimination based on disability, but it is not clear that it would apply to genetic risk assessments. Only California law explicitly applies to this situation and there have been no reported cases. PMID- 27256140 TI - Liver regeneration following repeated reversible portal vein embolization in an experimental model. AB - BACKGROUND: Portal vein embolization (PVE) is used routinely to prevent postoperative liver failure as a result of anticipated insufficient future liver remnant volume following resection. The authors have recently developed a technique for temporary PVE. The aim of this study was to assess the effect of repeated reversible PVE on hepatocyte proliferation and subsequent liver hypertrophy in rodents. METHODS: Four treatments were compared (n = 21 rats per group): single reversible PVE, two PVEs separated by 14 days, partial portal vein ligation or sham procedure. The feasibility and tolerance of the procedure were assessed. Volumetric imaging by CT was used to estimate the evolution of liver volumes. After death, the weight of liver lobes was measured and hepatocyte proliferation evaluated by immunostaining. RESULTS: Embolization of portal branches corresponding to 70 per cent of total portal flow was performed successfully in all animals. Repeated PVE induced additional hepatocyte proliferation. Repeated embolization resulted in superior hepatocyte proliferation in the non-occluded segments compared with portal vein ligation (31.1 versus 22.2 per cent; P = 0.003). The non-occluded to total liver volume ratio was higher in the repeated PVE group than in the single PVE and sham groups (P = 0.050 and P = 0.001 respectively). CONCLUSION: Repeated reversible PVE successfully induced additional hepatocyte proliferation and subsequent liver hypertrophy. Surgical relevance Portal vein embolization (PVE) is used routinely to prevent postoperative liver failure as a result of anticipated insufficient future liver remnant volume following resection. In the present study, a technique of repeated temporary PVE was developed in a rat model; this induced additional hepatocyte proliferation and an increase in liver volume compared with single embolization. This novel approach might help induce major hypertrophy of the future remnant liver, which could increase the rate of patients amenable to major liver resections. PMID- 27256139 TI - Interactions between amiodarone and the hERG potassium channel pore determined with mutagenesis and in silico docking. AB - The antiarrhythmic drug amiodarone delays cardiac repolarisation through inhibition of hERG-encoded potassium channels responsible for the rapid delayed rectifier potassium current (IKr). This study aimed to elucidate molecular determinants of amiodarone binding to the hERG channel. Whole-cell patch-clamp recordings were made at 37 degrees C of ionic current (IhERG) carried by wild type (WT) or mutant hERG channels expressed in HEK293 cells. Alanine mutagenesis and ligand docking were used to investigate the roles of pore cavity amino-acid residues in amiodarone binding. Amiodarone inhibited WT outward IhERG tails with a half-maximal inhibitory concentration (IC50) of ~45nM, whilst inward IhERG tails in a high K(+) external solution ([K(+)]e) of 94mM were blocked with an IC50 of 117.8nM. Amiodarone's inhibitory action was contingent upon channel gating. Alanine-mutagenesis identified multiple residues directly or indirectly involved in amiodarone binding. The IC50 for the S6 aromatic Y652A mutation was increased to ~20-fold that of WT IhERG, similar to the pore helical mutant S624A (~22-fold WT control). The IC50 for F656A mutant IhERG was ~17-fold its corresponding WT control. Computational docking using a MthK-based hERG model differentiated residues likely to interact directly with drug and those whose Ala mutation may affect drug block allosterically. The requirements for amiodarone block of aromatic residues F656 and Y652 within the hERG pore cavity are smaller than for other high affinity IhERG inhibitors, with relative importance to amiodarone binding of the residues investigated being S624A~Y652A>F656A>V659A>G648A>T623A. PMID- 27256141 TI - [Trends in indication of selected laboratory methods by general practitioners]. AB - The indication of laboratory methods in general practice is significantly influenced by practical guidelines and protocols for preventive care. The financial regulation pushes on rationalisation of the use of laboratory methods. Point of care testing is more and more important in prevention, diagnostics and follow up in primary care settings.Based on the data available from Skoda Insurance Company authors aimed to describe trends in induction and cost of laboratory methods, the most frequent methods used in primary care and trends in the use of POCT methods within general practice.The expenditures for laboratory methods in general practice are stable for a long term and suggest a rational behaviour of general practitioners. The most frequently indicated methods in general practice are glycaemia, ALT and AST. From expensive methods the most frequent are PSA, troponin and tumormarkers. The number of general practices performing POCT methods and also the number of POCT examinations increase. More than one half of INR examinations and nearly half of all CRP examinations are performed in POCT regime. KEY WORDS: laboratory methods, clinical biochemistry, general practitioner, primary care, POCT. PMID- 27256142 TI - [Potential sources of phthalates and bisphenol A and their significance in the development of metabolic diseases]. AB - Nowadays, there is increasing evidence showing that the development of the metabolic syndrome combining obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia involves except of traditional risk factors (overnutrition, lack of physical activity, genetic predisposition) also the effect of environmental organic substances called organic pollutants or endocrine disruptors. These chemicals can be found in plastic covers, paints, flame retardants, exhaust gases, fertilizers as well as diverse daily utensils. Phthalates, used primarily as plasticizers, and bisphenol A, are among the most wide-spread members of this group.The aim of this article is to provide a basic overview of the relationship between phthalates and bisphenol A and the etiopathogenesis of the metabolic syndrome and to highlight their potential sources. According to the analysis of materials used for parenteral nutrition and urinary excretion of phthalate metabolites and bisphenol A in subjects on long term parenteral nutrition we suppose that currently used medical materials are safe with respect to the exposure to both phthalates and bisphenol A and that home environment, especially cosmetic products, might constitute a more probable source of these substances. PMID- 27256143 TI - [Surgical treatment of lower extremity peripheral nerve injuries]. AB - Peripheral nerve injuries of the lower extremities are not frequent. The most common are traction injury of the peroneal nerve at the knee level or iatrogenic trauma of the pelvic nerves during abdominal surgery. Civil sharp injuries are rare.Indications for surgical revision follow the general rules of nerve surgery. Sharp injury should be treated as soon as possible, ideally within 72 hours. Closed lesions are indicated for surgery if a complete denervation remains unchanged three months after the injury. Best results can be achieved within six months from the injury. Irritations caused by bone fragments or scarring or by iatrogenic injury (clamps, cement, screws, etc.) may be revised later. However, the most important is early clinical examination in a specialized neurosurgical department. PMID- 27256144 TI - [Outpatient parenteral antibiotic therapy (OPAT)]. AB - Traditionally, parenteral (i. e. intravenous) antimicrobial therapy has been used in inpatients with various bacterial infections. In recent decades there has been growing experience with outpatient parenteral antimicrobial therapy, mainly in the USA and western Europe. This article provides basic information on OPAT, based on available literature and the author's experience on running OPAT service in the UK. PMID- 27256145 TI - [Faecal incontinence - serious medical and social issue]. AB - Faecal incontinence presents gastrointestinal disorder with high prevalence (more than 2% of population) and serious impact on the quality of life. General practitioners, gastroenterologists and colorectal surgeons play the principal role in screening, diagnostics and providing health care to patients who suffer from faecal incontinence. Insufficient knowledge about faecal incontinence and minimal training aimed at its diagnostics and therapy lead to the low quality of provided health care.Authors offer comprehensive up-to-date review focused on faecal incontinence - its definition, prevalence, seriousness, consequences, pathophysiology, diagnostics and management. Detailed anatomical and physiological assessment of each patient is fundamental in determining correct cause of faecal incontinence and consequent selection of the most appropriate therapeutic modality.Broad spectrum of available therapeutic options comprises conservative management (lifestyle modification, diet, medications, and absorbent tools), biofeedback and surgical interventions (sphincter augmentation, sphincter reconstruction, sacral nerve stimulation, sphincter substitution and stools diversion). Application of the most appropriate treatment can lead in majority of patients to significant improvement in faecal incontinence and quality of life. Early diagnosis prevents possible complications, which would possibly deteriorate patients quality of life. PMID- 27256146 TI - [Vesicoureteric reflux in children: many questions still unanswered]. AB - Vesicoureteric reflux (VUR) is the most common congenital anomaly of the uropoetic system. The gold standard for its diagnosis is the voiding cystourethrogram. Sonographic cystourethrography is an alternative method for reflux detection, but it is still not used routinely. Static scintigraphy enables us to diagnose renal scarring reflux nephropathy (RN). While congenital RN is a result of prenatal kidney injury, acquired RN results from pyelonephritis-induced renal damage.Risk factors for RN include VUR, recurrent APN, lower urinary tract dysfunction and delay in treatment of febrile urinary tract infection. Management of children after APN with VUR consists of antibiotic prophylaxy, surgery or surveillance only. The conclusions of performed studies are controversial, thus unified guidelines for the management of patients with VUR are not available. PMID- 27256147 TI - [Hyponatremia in children: from pathophysiology to therapy]. AB - This present review analyzes the etiology, diagnostics and management of conditions associated with hyponatremia. Excess water and/or sodium wasting lead to the development of hyponatremia in children. There are diverse etiologies associated with hyponatremia, correct diagnosis is based on detailed history, physical examination and basic laboratory tests. Symptomatic hyponatremia can be a life threatening emergency and thus requires fast and vigorous management. Inappropriate treatment may cause fatal consequences. PMID- 27256148 TI - [Role of incretins in energy metabolism and weight changes after smoking cessation]. AB - Incretine-based therapies are frequently used to treat patients with type 2 diabetes. Some of these drugs are used to induce weight loss. Liraglutide, a glucagon-like peptide 1 receptor agonist, was recently approved for the treatment of obesity. Smoking cessation is associated with weight gain. The mechanism responsible for the increase in body weight post cessation remains unclear. While increased caloric intake may play a role, weight gain may also be linked to nicotine, which has been shown to stimulate smokers basal metabolic rate. The effect of incretines on body weight and energy metabolism after smoking cessation is unclear. Recently published data suggests that incretine hormones may not be involved in the above mentioned changes. PMID- 27256149 TI - [Biobanks European infrastructure]. AB - Biobanks are structured repositories of human tissue samples connected with specific information. They became an integral part of personalized medicine in the new millennium. At the European research area biobanks are isolated not well coordinated and connected to the network. European commission supports European infrastructure BBMRI-ERIC (Biobanks and Biomolecular Resources Research Infrastructure European Research Infrastructure Consortium), consortium of 54 members with more than 225 associated organizations, largely biobanks from over 30 countries. The aim is to support biomedical research using stored samples. Czech Republic is a member of the consortium as a national node BBMRI_CZ, consisting of five partners. PMID- 27256150 TI - [Surgeons and Neurosurgeons as Nobel Prize Winners]. AB - Since 1901 Nobel Prize is awarded for exceptional achievements in physics, chemistry, literature, peace, economy (since 1968) and medicine or physiology. The first aim of the paper is to provide an overview of surgeons - winners of Nobel Prize for medicine or physiology. Although the prominent neurosurgeons were frequently nominated as Nobel Prize candidates, surprisingly no neurosurgeon received this prestigious award so far despite that the results of their research transgressed the relatively narrow limits of neurosurgical speciality.The most prominent leaders in the field of neurosurgery, such as Victor Horsley, Otfrid Foerster, Walter Dandy and Harvey Cushing are discussed from the point of their nominations. The overview of the activity of the Portuguese neurologists and Nobel Prize Winter in 1949 Egas Moniz (occasionally erroneously reported as neurosurgeon) is also provided. Although his work on brain angiography has fundamentally changed the diagnostic possibilities in neurology and neurosurgery, he was eventually awarded Nobel Prize for the introduction of the currently outdated frontal lobotomy.The fact that none of the above mentioned prominent neurosurgeons has not been recognised by Nobel Prize, may be attributed to the fact that their extensive work cannot be captured in a short summary pinpointing its groundbreaking character. PMID- 27256151 TI - Aromatase deficiency: a novel compound heterozygous mutation identified in a Chinese girl with severe phenotype and obvious maternal virilization. AB - BACKGROUND: Aromatase deficiency is a rare autosomal recessive disorder that is caused by an impairment of androgen conversion to estrogens. Affected 46, XX individuals generally present with virilization of external genitalia at birth and mutations in CYP19A1 gene. OBJECTIVE: This study described the clinical features and molecular basis of a Chinese 46, XX girl born with ambiguous genitalia and investigated the functional alteration of two novel mutations of the CYP19A1 gene. METHODS AND RESULTS: Obvious prepartum virilization and remarkably elevated testosterone were observed in the mother, who was initially suspected to have a testosterone-producing ovarian tumor. Clinical phenotypes and hormone profiles of the patient and her mother were investigated. Genotyping analyses of the CYP19A1 gene were performed in the patient and her parents. Functional impairment of the mutations was explored using three-dimensional computer model and mutagenesises in vitro transfection assays. A compound heterozygous mutation of the CYP19A1 gene was revealed in the patient, with a G deletion in nucleotide 264 of exon 3 in one allele and a 23-bp insertion in exon 9 in another allele; both mutations resulted in reading frame-shifts that led to truncated proteins of 87 and 360 amino acids, respectively. Molecular modeling analysis suggested that the two renascent truncated proteins lacked crucial amino acids that were involved in substrate access and catalysis as well as heme binding region. Functional studies in transfected HEK-293T cells exhibited a nearly complete abolishment of enzyme activity, which may underlie the phenotype and hormone profile. CONCLUSIONS: Two novel CYP19A1 mutations were identified in a Chinese girl born with ambiguous genitalia and severe maternal virilization during pregnancy. Maternal virilization should prompt consideration of aromatase deficiency, preventing unnecessary interventions in pregnancy. This study broadens the spectrum of phenotype and genetic mutations of this rare disorder. PMID- 27256152 TI - Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome. AB - Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Mullerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies. PMID- 27256153 TI - Process evaluation of a randomised controlled trial of a diabetes prevention intervention in Dutch primary health care: the SLIMMER study. AB - OBJECTIVE: To investigate (i) how the SLIMMER intervention was delivered and received in Dutch primary health care and (ii) how this could explain intervention effectiveness. DESIGN: A randomised controlled trial was conducted and subjects were randomly allocated to the intervention (10-month combined dietary and physical activity intervention) or the control group. A process evaluation including quantitative and qualitative methods was conducted. Data on process indicators (recruitment, reach, dose received, acceptability, implementation integrity and applicability) were collected via semi-structured interviews with health-care professionals (n 45) and intervention participant questionnaires (n 155). SETTING: SLIMMER was implemented in Dutch primary health care in twenty-five general practices, eleven dietitians, nine physiotherapist practices and fifteen sports clubs. SUBJECTS: Subjects at increased risk of developing type 2 diabetes were included. RESULTS: It was possible to recruit the intended high-risk population (response rate 54 %) and the SLIMMER intervention was very well received by both participants and health-care professionals (mean acceptability rating of 82 and 80, respectively). The intervention programme was to a large extent implemented as planned and was applicable in Dutch primary health care. Higher dose received and participant acceptability were related to improved health outcomes and dietary behaviour, but not to physical activity behaviour. CONCLUSIONS: The present study showed that it is feasible to implement a diabetes prevention intervention in Dutch primary health care. Higher dose received and participant acceptability were associated with improved health outcomes and dietary behaviour. Using an extensive process evaluation plan to gain insight into how an intervention is delivered and received is a valuable way of identifying intervention components that contribute to implementation integrity and effective prevention of type 2 diabetes in primary health care. PMID- 27256154 TI - Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study. AB - BACKGROUND: There is limited information about active tuberculosis (TB) occurring in psoriasis patients treated with Tumor necrosis factor (TNF) antagonists. OBJECTIVE: To describe the clinical characteristics of TB in psoriasis patients treated with TNF antagonists. METHODS: Nationwide retrospective study of psoriasis patients having experienced TB. Cases of TB were collected via three methods: search in the national pharmacosurveillance database, questionnaire to members of the French psoriasis research group, the college of French dermatology professors. We collected demographic data, TNF antagonist used, screening for latent tuberculosis infection, median time between TNF antagonists introduction and first symptoms, tests used for diagnosing TB infection, clinical features of tuberculosis and outcome. RESULTS: Eight centres reported 12 cases of TB between 2006 and 2014. They were nine men and three women with mean age of 49 years. All patients had adequate screening for latent tuberculosis. Three patients had stayed in endemic areas, three reported contact with a patient with TB. Tuberculosis presentation was extrapulmonary in 10 patients. Seven patients were treated with infliximab, four with adalimumab and one with certolizumab. The median time between TNF antagonist introduction and first symptoms of tuberculosis was 23.4 weeks (2-176). Six of the 12 patients had a positive direct examination and/or positive culture for Mycobacterium tuberculosis. Histological samples of affected organs taken from seven patients showed granulomatous inflammation in six, with caseating necrosis in five. Two of the 12 patients died of disseminated TB. CONCLUSION: This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with suggestive symptoms and organ involvement. PMID- 27256155 TI - A Novel Automated High-Content Analysis Workflow Capturing Cell Population Dynamics from Induced Pluripotent Stem Cell Live Imaging Data. AB - Most image analysis pipelines rely on multiple channels per image with subcellular reference points for cell segmentation. Single-channel phase-contrast images are often problematic, especially for cells with unfavorable morphology, such as induced pluripotent stem cells (iPSCs). Live imaging poses a further challenge, because of the introduction of the dimension of time. Evaluations cannot be easily integrated with other biological data sets including analysis of endpoint images. Here, we present a workflow that incorporates a novel CellProfiler-based image analysis pipeline enabling segmentation of single channel images with a robust R-based software solution to reduce the dimension of time to a single data point. These two packages combined allow robust segmentation of iPSCs solely on phase-contrast single-channel images and enable live imaging data to be easily integrated to endpoint data sets while retaining the dynamics of cellular responses. The described workflow facilitates characterization of the response of live-imaged iPSCs to external stimuli and definition of cell line-specific, phenotypic signatures. We present an efficient tool set for automated high-content analysis suitable for cells with challenging morphology. This approach has potentially widespread applications for human pluripotent stem cells and other cell types. PMID- 27256156 TI - A Comparative Study of Liver Disease Care in the USA and Urban and Rural China. AB - BACKGROUND: Chronic liver disease is a major cause of morbidity and mortality in the USA and China, but the etiology of liver disease, medical practice, and patient expectations in these two countries are different. AIMS: To compare patient knowledge about their liver disease, patient satisfaction with liver disease care, and patient medical decision-making preference in the USA and China. METHODS: Three cohorts of established adult patients with liver disease seen in liver clinics in Ann Arbor, USA, and Beijing (urban) and Hebei (rural), China, completed a survey between May and September 2014. RESULTS: A total of 990 patients (395 USA, 398 Beijing, and 197 Hebei) were analyzed. Mean liver disease knowledge score (maximum 5) in the USA, Beijing, and Hebei patients was 4.1, 3.6, and 3.0, respectively (p < 0.001). US patients had a greater preference for collaborative decision-making: 71.8 % preferred to make treatment decisions together with the doctor, while most Chinese patients (74.6 % Beijing and 84.8 % Hebei) preferred passive decision-making. Mean satisfaction score (maximum 85) in the USA was higher than in Beijing, which in turn was higher than in Hebei (78.2 vs. 66.5 vs. 60.3, p < 0.001). There was a positive correlation between liver disease knowledge score and satisfaction score (r = 0.27, p < 0.001) and with collaborative medical decision-making (r = 0.22, p < 0.001) when responses from all sites were combined. CONCLUSIONS: Liver disease knowledge and patient satisfaction were greatest in the USA, followed by Beijing and then Hebei patients. Understanding these differences and associated factors may help to improve patient outcomes. PMID- 27256157 TI - Cervical Infection With Vaccine-Associated Human Papillomavirus (HPV) Genotypes as a Predictor of Acquisition and Clearance of Other HPV Infections. AB - BACKGROUND: Recent birth cohorts vaccinated against human papillomavirus (HPV) may be protected against up to 4 genotypes (HPV-6, -11, -16, and -18). If natural competition exists between these and other HPV types, then the prevalence of other types may increase after vaccination. METHODS: Cohort information from 3 studies was used to compare acquisition and clearance of 30 different HPV types (individually and grouped by species), according to infection status with vaccine targeted types at baseline and the time of the index infection, respectively. Hazard ratios (HRs) were adjusted for predictors of multiple-type infection. RESULTS: Among 3200 females across all studies, 857 were infected with HPV at baseline, and 994 acquired new infections during follow-up. Females infected with HPV-16 were at higher risk of acquiring other alpha-9 HPV types (HR, 1.9; 95% confidence interval [CI], 1.2-3.0) but at similar risk of clearing existing alpha 9 HPV infections (HR, 0.9; 95% CI, .7-1.3). Females infected with vaccine targeted types were generally at higher risk of acquiring additional types (HRs, > 1.0) and at equal risk of clearing existing infections. Accounting for multiple comparisons, none of the HRs of < 1.0 or >1.0 were statistically significant in our analyses of acquisition or clearance. CONCLUSIONS: Vaccine-targeted HPV types do not appear to compete with other types, suggesting that HPV type replacement is unlikely to occur. PMID- 27256158 TI - Novel analogs of allopregnanolone show improved efficiency and specificity in neuroprotection and stimulation of proliferation. AB - The natural neurosteroid allopregnanolone exerts beneficial effects in animal models of neurodegenerative diseases, nervous system injury and peripheral neuropathies. It not only has anti-apoptotic activity, but also promotes proliferation of progenitor cells. With respect to using it as a therapeutic tool, such pleiotropic actions might create unwanted side effects. Therefore, we have synthesized allopregnanolone analogs and analyzed their neuroprotective and proliferative effects to identify compounds with higher efficiency and less ambiguous biological actions. Proliferation-promoting effects of 3alpha and 3beta isomers of 3-O-allyl-allopregnanolone and 12 oxo-allopregnanolone were studied in adult subventricular zone stem cell cultures and in primary hippocampal cultures by measuring 5-ethynyl-2'-deoxyuridine incorporation. Neuroprotective activity against amyloid beta 42-induced cell death was determined by quantifying caspase 3/7 activity. The 3alpha isomers significantly stimulated proliferation in all culture systems, whereas the 3beta isomers were ineffective. The stimulatory effect of 3alpha-O-allyl-allopregnanolone was significantly higher than that of allopregnanolone. In neural stem cell cultures, 3alpha-O-allyl-allopregnanolone specifically enhanced proliferation of Nestin-positive progenitors. In addition, it promoted the differentiation of doublecortin-positive neurons. In neural stem cell cultures treated with amyloid beta 42, both the alpha and beta isomers of O allyl- allopregnanolone showed increased neuroprotective activity as compared to allopregnanolone, completely preventing amyloid-induced caspase 3/7 activation. The 12 oxo-allopregnanolone analogs were ineffective. These results identify structural allopregnanolone analogs with higher anti-apoptotic and proliferation promoting activity than the natural neurosteroid. Interestingly, stereoisomers of the analogs were found to have distinct profiles of activity raising the possibility of exploiting the neuroprotective properties of neurosteroids with or without simultaneously stimulating neurogenesis. Cover Image for this issue: doi: 10.1111/jnc.13344. PMID- 27256159 TI - Evolution of Dermatofibrosarcoma Protuberans to DFSP-Derived Fibrosarcoma: An Event Marked by Epithelial-Mesenchymal Transition-like Process and 22q Loss. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare and indolent cutaneous sarcoma. At times, a fibrosarcomatous transformation marked by a more aggressive clinical behavior may be present. We investigated the natural history and the molecular bases of progression from classic DFSP to the fibrosarcomatous form (FS-DFSP), looking, retrospectively, at the outcome of all patients affected by primary DFSP treated at our institution from 1993 to 2012 and analyzing the molecular profile of 5 DFSPs and 5 FS-DFSPs by an integrated genomics approach (whole transcriptome sequencing, copy number analysis, FISH, qRT-PCR, IHC). The presence of fibrosarcomatous features was identified in 20 (7.6%) patients out of 263 DFSP. All cases were treated with macroscopic complete surgery. A local relapse occurred in 4 of 23 patients who received a microscopic marginal surgery (2 classic DFSP, 2 FS-DFSP), while metastasis affected 2 patients, both FS-DFSP (10% of FS-DFSP), being the first event. DFSP evolution to FS-DFSP was paralleled by a transcriptional reprogramming. The recurrent loss of chromosome 22q appeared to contribute to this phenomenon by promoting the expression of epigenetic regulators, such as EZH2. Loss of the p16/CDKN2A/INK4A locus at 9p was also observed in two FS-DFSP metastatic cases. IMPLICATIONS: FS-DFSP is a rare subgroup among DFSP, with a 10% metastatic risk, that was independent from local recurrence and that was not observed in DFSP, that were all cured by wide surgery. Chromosome 22q deletion might play a role in FS-DFSP, and p16 loss may convey a poor outcome. EZH2 dysregulation was also found and represents a druggable target. Mol Cancer Res; 14(9); 820-9. (c)2016 AACR. PMID- 27256160 TI - ROS1 fusions in cancer: a review. AB - The ROS1 gene belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. A literature review identified a ROS1 fusion in 2.54% of the patients with lung adenocarcinoma and even higher frequencies in spitzoid neoplasms and inflammatory myofibroblastic tumors. At present, 26 genes were found to fuse with ROS1, some of them already known to fuse with RET and ALK. All the fusion proteins retain the ROS1 kinase domain, but rarely its transmembrane domain. Most of the partners have dimerization domains that are retained in the fusion, presumably leading to constitutive ROS1 tyrosine kinase activation. Some partners have transmembrane domains that are retained or not in the chimeric proteins. Therefore, different ROS1 fusions have distinct subcellular localization, suggesting that they may activate different substrates in vivo. PMID- 27256161 TI - Preschoolers' generosity increases with understanding of the affective benefits of sharing. AB - Research has demonstrated that sharing with others is rewarding, suggesting a proximal mechanism of humans' extraordinary tendency to engage in prosocial behavior. The current study explored the cognitive basis of the relation between generosity and happiness early in ontogeny. We demonstrate that preschool children understand the relation between generosity and happiness. Moreover, our results show that children's emotion ratings are predictive for their subsequent sharing behavior. This finding provides evidence for the theoretical claim that prosocial behavior may be related to the anticipation of positive feelings, and that this mechanism may explain early instances of generosity in preschool children. PMID- 27256162 TI - A Cross-Sectional Clinic-Based Study in Patients With Side-Locked Unilateral Headache and Facial Pain. AB - OBJECTIVE: To undertake the epidemiological evaluation of the patients presenting with side-locked headache and facial pain in a tertiary neurology outpatient clinic. BACKGROUND: Side-locked unilateral headache and facial pain include a large number of primary and secondary headaches and cranial neuropathies. A diagnostic approach for the patients presenting with strictly unilateral headaches is important as many of these headache disorders respond to a highly selective drug. Epidemiological data may guide us to formulate a proper approach for such patients. However, the literature is sparse on strictly unilateral headache and facial pain. METHODS: We prospectively recruited 307 consecutive adult patients (>18 years) with side-locked headache and facial pain presenting to a neurology outpatient clinic between July 2014 and December 2015. All patients were subjected to MRI brain and other investigations to find out the different secondary causes. The diagnosis was carried out by at least two headache specialists together. All patients were classified according to the International Classification of Headache Disorder-third edition (ICHD-3beta). RESULTS: The mean age at the time of examination was 42.4 +/- 13.6 years (range 18-80 years). Forty-eight percent of patients were male. Strictly unilateral headaches accounted for 19.2% of the total headaches seen in the clinic. Headaches were classified as primary in 58%, secondary in 18%, and cranial neuropathies and other facial pain in 16% patients. Five percent of patients could not be classified. Three percent of patients were classified as per the Appendix section of ICHD-3beta. The prevalence of secondary headaches and painful cranial neuropathies increased with age. A total of 36 different diagnoses were made. Only two diseases (migraine and cluster headache) had a prevalence of more than 10%. The prevalence of 13 diseases varied between 6 and 9%. The prevalence of other 14 groups was <=1%. Migraine was the most common diagnosis (15%). Cervicogenic headache was the most common secondary headache. Classical trigeminal neuralgias and persistent idiopathic facial pain were two most common diagnoses in the painful cranial neuropathies and other facial pain groups. Sixty one percent fulfilled the definition of chronic daily headaches, and hemicrania continua and cervicogenic headache were the two most common diagnoses in this group. CONCLUSIONS: A large number of primary and secondary headaches and cranial neuropathies may present as side-locked headache and facial pain syndromes. Therefore, a sound knowledge of diagnostic approach is required for the optimal management of side locked headaches and facial pain. PMID- 27256163 TI - Erratum: Nanoelectronic primary thermometry below 4 mK. PMID- 27256164 TI - Role of UCP2 polymorphisms on dietary intake of obese patients who underwent bariatric surgery. AB - Uncoupling protein 2 ( UCP2 ) plays an important role in body weight and energy metabolism and may be related to the control of food consumption. This study aimed to investigate the contribution of UCP2 gene variants on the dietary intake on a population after bariatric surgery. This study enrolled 150 obese patients (body mass index >= 35kg m(-2) ) who submitted to Roux-en-Y gastric bypass. Weight (kg), BMI (kg m(-2) ), energy (kcal d(-1) ) and macronutrients intake (g d(-1) ) of preoperative and 1-year postoperative period were collected from medical records. Ala55Val and -866G>A polymorphisms in the UCP2 gene were genotyped through allelic discrimination method in real-time polymerase chain reaction using the TaqMan pre-designed SNP Genotyping Assays kits. Hardy-Weinberg equilibrium, t-test and regression models were performed in statistical analysis (P<0.05).We found an allelic frequency of 0.44 for allele Val and 0.41 for allele A. In the postoperative period, patients with at least one rare allele for polymorphisms and with at least one rare allele for both polymorphisms together (haplotype) present a greater energy and carbohydrate intake, even after adjusting for gender, age and weight. Genetic variants in UCP2 gene were associated with the dietary consumption after Roux-En-Y gastric bypass. PMID- 27256165 TI - TRUNCATION ARTIFACT IN MAGNETIC RESONANCE IMAGES OF THE CANINE SPINAL CORD. AB - The truncation artifact in magnetic resonance (MR) images is a line of abnormal signal intensity that occurs parallel to an interface between tissues of markedly different signal intensity. In order to demonstrate the truncation artifact in sagittal images of the canine spinal cord and the effect of changing spatial resolution, we conducted an experimental in vitro study. A section of fixed canine spinal cord was imaged using a 1.5T magnet. Spatial resolution was increased by increasing the acquisition matrix and reconstruction matrix, producing series of T2-weighted (T2w) images with the following pixel sizes: A, 1.6 (vertical) * 2.2 mm2 (horizontal); B, 1.2 * 1.7 mm2 ; C, 0.8 * 1.1 mm2 ; D, 0.4 * 0. 6 mm2 . Plots of mean pixel value across the cord showed variations in signal intensity compatible with truncation artifact, which appeared as a single, wide central hyperintense zone in low-resolution images and as multiple narrower zones in high spatial resolution images. Even in images obtained using the highest spatial resolution available for the MR system, the edge of the spinal cord was not accurately defined and the central canal was not visible. The experiment was repeated using an unfixed spinal cord specimen with focal compression applied to mimic a pathologic lesion. Slight hyperintensity was observed within the spinal cord at the site of compression although the cord was normal histologically. Results of this study suggest that caution should be applied when interpreting hyperintensity affecting the spinal cord in T2w sagittal images of clinical patients because of the possibility that the abnormal signal could represent a truncation artifact. PMID- 27256166 TI - Lemierre's syndrome. PMID- 27256167 TI - Remarkable preservation of Ca(2+) homeostasis and inhibition of apoptosis contribute to anti-muscle atrophy effect in hibernating Daurian ground squirrels. AB - The underlying mechanisms that hibernators deviated from muscle atrophy during prolonged hibernating inactivity remain elusive. This study tested the hypothesis that the maintenance of intracellular Ca(2+) homeostasis and inhibition of apoptosis would be responsible for preventing muscle atrophy in hibernating Daurian ground squirrels. The results showed that intracellular Ca(2+) homeostasis was maintained in soleus and extensor digitorum longus (EDL) in hibernation and post-hibernation, while cytosolic Ca(2+) was overloaded in gastrocnemius (GAS) in hibernation with a recovery in post-hibernation. The Ca(2+) overload was also observed in interbout arousals in all three type muscles. Besides, the Bax/Bcl-2 ratio was unchanged in transcriptional level among pre-hibernation, hibernation and interbout arousals, and reduced to a minimum in post-hibernation. Furthermore, the Bax/Bcl-2 ratio in protein level was reduced in hibernation but recovered in interbout arousals. Although cytochrome C was increased in GAS and EDL in post-hibernation, no apoptosis was observed by TUNEL assay. These findings suggested that the intracellular Ca(2+) homeostasis in hibernation might be regulated by the cytosolic Ca(2+) overload during interbout arousals, which were likely responsible for preventing muscle atrophy via inhibition of apoptosis. Moreover, the muscle-specificity indicated that the different mechanisms against disuse-induced atrophy might be involved in different muscles in hibernation. PMID- 27256168 TI - Proopiomelanocortin interference in the measurement of adrenocorticotrophic hormone: a United Kingdom National External Quality Assessment Service study. AB - OBJECTIVE: It is recognized that measurement of ACTH-precursor peptides including proopiomelanocortin (POMC) has clinical utility in identifying the aetiology of Cushing's syndrome. Recent data have also demonstrated cross-reactivity of POMC in ACTH immunoassays used in clinical laboratories. The aim of this study was to assess the cross-reactivity of POMC in the main commercial immunoassays for ACTH and to survey the awareness of laboratory professionals to this potential interference. METHOD: To assess cross-reactivity, specimens containing ACTH and/or POMC were prepared by the UK National External Quality Assessment Service (UK NEQAS) [Edinburgh]. A separate interpretative exercise was also sent to participating laboratories. RESULTS: Eighty-seven laboratories measured 'total' ACTH (i.e. ACTH and/or POMC) in their assays. Cross-reactivity of POMC varied from a mean of 1.6-4.7% (reflected in a large percentage increase in measured ACTH of up to 261% due to POMC cross-reactivity) depending on the manufacturer. Major differences in the clinical interpretation of test results were observed in returned responses to the interpretative exercise. CONCLUSION: An appraisal of POMC cross-reactivity in currently available ACTH immunoassays has been achieved. Cross-reactivity was sufficient to detect ACTH precursors at concentrations that could be found in patients with ectopic ACTH syndrome. These data will assist laboratories in interpreting results when assessing the hypothalamic-pituitary adrenal axis. Endocrinologists and laboratory professionals should be aware of the degree of cross-reactivity in ACTH immunoassay in order to minimize the risk of misinterpretation of results and/or potentially delayed treatment. PMID- 27256169 TI - High levels of beta-xylosidase in Thermomyces lanuginosus: potential use for saccharification. AB - A new strain of Thermomyces lanuginosus was isolated from the Atlantic Forest biome, and its beta-xylosidases optimization in response to agro-industrial residues was performed. Using statistical approach as a strategy for optimization, the induction of beta-xylosidases activity was evaluated in residual corn straw, and improved so that the optimum condition achieved high beta-xylosidases activities 1003U/mL. According our known, this study is the first to show so high levels of beta-xylosidases activities induction. In addition, the application of an experimental design with this microorganism to induce beta-xylosidases has not been reported until the present work. The optimal conditions for the crude enzyme extract were pH 5.5 and 60 degrees C showing better thermostability at 55 degrees C. The saccharification ability of beta xylosidase in the presence of hemicellulose obtained from corn straw raw and xylan from beechwood substrates showed a xylo-oligosaccharide to xylose conversion yield of 80 and 50%, respectively, at 50 degrees C. Our data strongly indicated that the beta-xylosidases activities was not subjected to the effects of potential enzyme inhibitors often produced during fermentation process. These data suggest the application of this enzyme studied for saccharification of hemicellulose, an abundant residue in the American continents, thus providing an interesting alternative for future tests for energy production. PMID- 27256170 TI - Stroke Thrombolysis Protocol Shortens "Door-to-Needle Time" and Improves Outcomes Experience at a Tertiary Care Center in Qatar. AB - BACKGROUND AND PURPOSE: To assess the effect of acute thrombolysis protocol on "door-to-needle time" (DTN) and improvement in outcome following acute stroke (AS). METHODS: The charts of all patients receiving intravenous (IV) thrombolysis for AS between January 2008 and June 2015 were reviewed for DTN, complications, and clinical outcome. Good prognosis was defined as modified Rankin Scale (mRS) score of less than 2 at 90 days. In January 2014, a protocol for faster DTN was introduced. We reviewed the prognosis before and after the introduction of the new protocol. RESULTS: Up to 204 patients received IV recombinant tissue plasminogen activator (r-tPA) (mean age 52.5 +/- 12.4 years). Mean door-to-CT time improved from 42.5 +/- 41.1 to 27.1 +/- 26.3 minutes (P < .001); DTN improved from 83.26 +/- 47.7 to 47.09 +/- 25.7 minutes (P < .001). Complications were reduced from 15.7% to 8.8% (P = .14). The mRS score of less than or equal to 2 improved from 47.1% to 73.3% at 90 days (P = .001). After implementing new protocol, thrombolysis rate increased to 11.8% in 2014 (before 3.3% in 2011, 4.9% in 2012, and 4.4% in 2013), P < .0001. NIHSS (National Institutes of Health Stroke Scale) score at admission (P = .002), hypodensity on initial CT brain (P = .041), protocol implementation (P = .014), and reduced length of stay (P = .004) were associated with outcome at 90 days (mRS score <=2). CONCLUSION: Implementation of specific protocols to reduce DTN in patients receiving IV r-tPA leads to reduction in complications and improves outcome. PMID- 27256171 TI - Four-Dimensional Computed Tomography Angiography Demonstrating a Ruptured Basilar Artery Aneurysm Causing Anterior Cerebral Circulation Arrest. AB - A 61-year-old woman suffered a pronounced subarachnoid hemorrhage. Conventional computed tomography angiography (CTA) showed no enhancement of the intracranial vasculature, whereas there was normal contrast enhancement of bilateral external carotid artery branches. Subsequent four-dimensional computed tomography angiography (4D-CTA) demonstrated active contrast leakage out of a ruptured basilar tip aneurysm, whereas there was no enhancement of the anterior circulation at any time point, consistent with intracranial anterior circulation arrest. This case illustrates that 4D-CTA is superior to conventional CTA for the evaluation of intracranial flow dynamics and delayed intracranial vascular contrast filling. PMID- 27256172 TI - Association between Serum Lipid Profiles and Early Neurological Deterioration in Acute Ischemic Stroke. AB - BACKGROUND: Dyslipidemia is associated with chronic cardiovascular disease. However, the effect of dyslipidemia on acute ischemic stroke is unclear. We hypothesized that dyslipidemia could contribute to early neurological deterioration (END) after ischemic stroke. METHODS: A total of 410 acute ischemic stroke patients who were admitted to our stroke center within 24 hours after ictus were consecutively included in this study. END was defined as any new neurological symptoms/signs or any neurological worsening occurring during the admission and/or within 3 weeks after the index stroke. Multivariable logistic regression was used to examine the independent association between lipid indices and END. RESULTS: Mean age was 68.2 +/- 13.3 years, 241 (58.8%) were male, and 78 (19.0%) experienced END. Almost END occurred within 3 days after admission (n = 70, 89.7%), and the majority of END was stroke progression (n = 68, 87.1%). In univariate analysis, high-density lipoprotein (HDL)-cholesterol levels (per 1 mmol/L; odds ratio [OR] .37; 95% CI .17-.80; P = .012) and apolipoprotein B (apoB)/apoA-I ratio (per 1 increase; OR 3.71; 95% CI 1.48-9.29; P = .005) were associated with END. In the multivariable analysis, adjusted ORs of END for the highest quartile of HDL-cholesterol and apoB/apoA-I ratio were .42 (95% CI .19 .94; P = .034) and 2.37 (95% CI 1.02-5.53; P = .045), respectively. The ratio of apoB/apoA-I was associated with END in large artery atherosclerosis stroke but not in other stroke subtypes. CONCLUSIONS: Independent association of low HDL cholesterol and high apoB/apoA-I ratio with END warrants further research to investigate if correction of the lipid profile during the acute period of ischemic stroke could reduce the risk of END. PMID- 27256173 TI - Predictive Ability of an Emergency Medical Dispatch Stroke Diagnostic Tool in Identifying Hospital-Confirmed Strokes. AB - BACKGROUND: Early hospital notification of a possible stroke arriving via emergency medical services (EMS) can prepare stroke center personnel for timely treatment, especially timely administration of tissue plasminogen activator. Stroke center notification from the emergency dispatch center-before responders reach the scene-may promote even earlier and faster system activation, meaning that stroke center teams may be ready to receive patients as soon as the ambulance arrives. This study evaluates the use of a Medical Priority Dispatch System (MPDS; Priority Dispatch Corp., Salt Lake City, UT) Stroke Diagnostic Tool (SDxT) to identify possible strokes early by comparing the tools' results to on scene and hospital findings. METHODS: The retrospective descriptive study utilized stroke data from 3 sources: emergency medical dispatch, EMS, and emergency department/hospital. RESULTS: A total of 830 cases were collected between June 2012 and December 2013, of which 603 (72.7%) had matching dispatch records. Of the 603 cases, 304 (50.4%) were handled using MPDS Stroke Protocol 28. The SDxT had an 86.4% ability (OR [95% CI]: 2.3 [1.5, 3.5]) to effectively identify strokes among all the hospital-confirmed stroke cases (sensitivity), and a 26.6% ability to effectively identify nonstrokes among all the hospital confirmed nonstroke cases (specificity). CONCLUSIONS: The SDxT demonstrated a very high sensitivity, compared to similar tools used in the field and at dispatch. The specificity was somewhat low, but this was expected-and is intended in the creation of protocols to be used over the phone in emergency situations. The tool is a valuable method for identifying strokes early and may allow early hospital notification. PMID- 27256174 TI - "Total reconstruction" of the urethrovesical anastomosis contributes to early urinary continence in laparoscopic radical prostatectomy. AB - PURPOSE: To demonstrate the effect of total reconstruction technique on postoperative urinary continence after laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: LRP was performed using a standard urethrovesical anastomosis in 79 consecutive patients (Group-A) from June 2011 to October 2012, and a total reconstruction procedure in 82 consecutive patients (Group-B) from June 2012 to June 2013. The primary outcome measurement was urinary continence assessed at 1, 2, 4, 12, 24 and 52 weeks after catheter removal. Other data recorded were patient age, body mass index, International Prostate Symptoms Score, prostate volume, preoperative PSA, Gleason score, neurovascular bundle preservation, operation time, estimated blood loss, complications and pathology results. RESULTS: In Group-A, the continence rates at 1, 2, 4, 12, 24 and 52 weeks were 7.59%, 20.25%, 37.97%, 58.22%, 81.01% and 89.87% respectively. In Group-B, the continence rates were 13.41%, 32.92%, 65.85%, 81.71%, 90.24% and 95.12% respectively. Group-B had significantly higher continence rates at 4 and 12 weeks after surgery (P<0.001 and P=0.001). There were no significant differences between the groups with respect to patient's age, body mass index, prostate-specific antigen level, prostate volume, IPSS, estimated blood loss, number of nerve-sparing procedures and postoperative complications. CONCLUSIONS: Total reconstruction technique in the procedure of urethrovesical anastomosis during LRP improved early recovery of continence. PMID- 27256175 TI - Laparoscopic versus open radical prostatectomy in high prostate volume cases: impact on oncological and functional results. AB - BACKGROUND AND OBJECTIVE: To prospectively compare the laparoscopic versus open approach to RP in cases with high prostate volume and to evaluate a possible diferente impact of prostate volume. MATERIALS AND METHODS: From March 2007 to March 2013 a total of 120 cases with clinically localized prostate cancer (PC) and a prostate volume>70cc identified for radical prostatectomy (RP), were prospectively analyzed in our institute. Patients were offered as surgical technique either an open retropubic or an intraperitoneal laparoscopic (LP) approach. In our population, 54 cases were submitted to LP and 66 to open RP. We analyzed the association of the surgical technique with perioperative, oncological and postoperative functional parameters. RESULTS: In those high prostate volume cases, the surgical technique (laparoscopic versus open) does not represent a significant independent factor able to influence positive surgical margins rates and characteristics (p=0.4974). No significant differences (p>0.05) in the overall rates of positive margins was found, and also no differences following stratification according to the pathological stage and nerve sparing (NS) procedure. The surgical technique was able to significantly and independently influence the hospital stay, time of operation and blood loss (p<0.001). On the contrary, in our population, the surgical technique was not a significant factor influencing all pathological and 1-year oncological or functional outcomes (p>0.05). CONCLUSIONS: In our prospective non randomized analysis on high prostate volumes, the laparoscopic approach to RP is able to guarantee the same oncological and functional results of an open approach, maintaining the advantages in terms of perioperative outcomes. PMID- 27256176 TI - Is [F-18]-fluorodeoxyglucose FDG-PET/CT better than ct alone for the preoperative lymph node staging of muscle invasive bladder cancer? AB - OBJECTIVE: To evaluate whether the use of [F-18]-FDG-PET/CT can accurately predict pelvic lymph node metastasis in patients with muscle invasive TCC of the bladder undergoing radical cystectomy. MATERIALS AND METHODS: Fifteen patients with muscle invasive bladder cancer had undergone FDG-PET/CT scan from the skull base to the mid-thighs after IV injection of 6.5MBq (Mega-Becquerel)/Kg of FDG. After intravenous hydration IV furosemide was given to overcome the difficulties posed by urinary excretion of 18F-FDG. PET/ CT data were analyzed as PET and CT images studied separately as well as fused PET/ CT images. The imaging findings were correlated with the histopathology of the nodes (gold standard). RESULTS: CT and FDG-PET had demonstrated positive lymph nodes in 9 & 8 patients respectively. Among the 15 patients 3 had documented metastasis on histopathology. Both CT and PET could detect the nodes in all these 3 patients (100% sensitivity). Nodes were histologically negative amongst 6&5 patients who had node involvement by CT and PET respectively. Therefore, specificity, positive predictive value (PPV) & negative predictive value (NPV) for CT and PET/CT were 50%, 33.3%, 100% and 58.3%, 37.5%, 100% respectively. CONCLUSION: The theoretical advantage of this cutting edge technology for whole body imaging has not been translated into clinical practice as we found minimal advantage of combined FDG-PET/CT over CT alone for nodal staging of muscle invasive bladder cancer. This may be due to substantial overlap between standardized uptake values (SUVs) from active inflammatory processes with those of malignant lesion. PMID- 27256177 TI - Urothelial neoplasm of the bladder in childhood and adolescence: a rare disease. AB - PURPOSE: Bladder tumors are rare in children and adolescents. For this reason, the diagnosis is sometimes delayed in pediatric patients. We aimed to describe the diagnosis, treatment, and follow-up methods of bladder urothelial neoplasms in children and adolescents. MATERIALS AND METHODS: We carried out a retrospective multicenter study involving patients who were treated between 2008 and 2014. Eleven patients aged younger than 18 years were enrolled in the study. In all the patients, a bladder tumor was diagnosed using ultrasonography and was treated through transurethral resection of the bladder (TURBT). RESULTS: Nine of the 11 patients (82%) were admitted with gross hematuria. The average delay in diagnosis was 3 months (range, 0-16 months) until the ultrasonographic diagnosis was performed from the first episodes of macroscopic hematuria. A single exophytic tumor (1-4cm) was present in each patient. The pathology of all patients was reported as superficial urothelial neoplasm: two with papilloma, one with papillary urothelial neoplasm of low malignant potential (PUNLMP), four with low grade pTa, and four with low grade pT1. No recurrence was observed during regular cystoscopic and ultrasonographic follow-up. CONCLUSIONS: Regardless of the presence of hematuria, bladder tumors in children are usually not considered because urothelial carcinoma in this population is extremely rare, which causes a delay in diagnosis. Fortunately, the disease has a good prognosis and recurrences are infrequent. Cystoscopy may be unnecessary in the follow-up of children with bladder tumors. We believe that ultrasonography is sufficient in follow-up. PMID- 27256178 TI - Low grade urothelial carcinoma mimicking basal cell hyperplasia and transitional metaplasia in needle prostate biopsy. AB - PURPOSE: The vast majority of urothelial carcinomas infiltrating the bladder are consistente with high-grade tumors that can be easily recognized as malignant in needle prostatic biopsies. In contrast, the histological changes of low-grade urothelial carcinomas in this kind of biopsy have not been studied. MATERIALS AND METHODS: We describe the clinicopathologic features of two patients with low grade bladder carcinomas infiltrating the prostate. They reported dysuria and hematuria. Both had a slight elevation of the prostate specific antigen and induration of the prostatic lobes. Needle biopsies were performed. At endoscopy bladder tumors were found in both cases. RESULTS: Both biopsies showed nests of basophilic cells and cells with perinuclear clearing and slight atypia infiltrating acini and small prostatic ducts. The stroma exhibited extensive desmoplasia and chronic inflammation. The original diagnosis was basal cell hyperplasia and transitional metaplasia. The bladder tumors also showed low-grade urothelial carcinoma. In one case, the neoplasm infiltrated the lamina propria, and in another, the muscle layer. In both, a transurethral resection was performed for obstructive urinary symptoms. The neoplasms were positive for high molecular weight keratin (34BetaE12) and thrombomodulin. No metastases were found in either of the patients, and one of them has survived for five years. CONCLUSIONS: The diagnosis of low-grade urothelial carcinoma in prostate needle biopsies is difficult and may simulate benign prostate lesions including basal cell hyperplasia and urothelial metaplasia. It is crucial to recognize low-grade urothelial carcinoma in needle biopsies because only an early diagnosis and aggressive treatment can improve the prognosis for these patients. PMID- 27256179 TI - Functional and oncologic outcomes after nephron-sparing surgery in a solitary kidney: 10 years of experience. AB - OBJECTIVES: To evaluate functional and oncologic outcomes of partial nephrectomy (PN) in patients with a solitary kidney. MATERIALS AND METHODS: A retrospective analysis of patients with a solitary kidney undergoing nephron-sparing surgery between March 2003 and March 2013 was performed. GFR was recorded before the procedure and 3 months after surgery, thus establishing a change (cGFR). Several variables that may influence cGFR were analyzed. Complications are herein described, namely bleeding, fistula, acute renal failure and end-stage renal disease (ESRD). Local recurrence and margin status are also described. Survival rates were calculated using the Kaplan Meier method (2 patients with metastasis at the time of surgery were excluded from the analysis). RESULTS: Forty-five patients were available for analysis. Median follow-up was 27.56 months (r 3-96). Mean cGFR was-7.12mL/min (SD 2.1). Variables significantly related with lower GFR after surgery were loss of renal mass (p=0.01)) and male gender (p=0.03). Four patients (8.8%) experienced hemorrhage. Nine patients (20%) developed a urinary fistula. Only one patient with bleeding required open surgery. Two patients (4.4%) needed transient dialysis. Three patients (6.6%) developed ESRD. Four patients (8.8%) had positive surgical margins (PSMs) and four patients (88%) had local recurrence (2 of these had PSMs). Five patients (11.1%) died during follow up. Four patients (8.8%) died because of renal cancer. Estimated 2-year overall survival, disease-free survival and cancer specific survival rates were 88.4% (CI 95% 70.5-96); 87.7% (CI 95% 68.1-96) and 92.4% (CI 95% 75-98), respectively. CONCLUSION: Loss of renal mass and male gender were associated with lower postoperative GFR. Our outcomes were comparable with those in the World literature. PMID- 27256180 TI - Outcome and complications of percutaneous nephrolithotomy as primary versus secondary procedure for renal calculi. AB - PURPOSE: To compare the efficacy of percutaneous nephrolithotomy (PCNL) as a primary procedure of patients following previous open surgery or post percutaneous nephrolithotomy (PCNL) for renal calculi. MATERIALS AND METHODS: The medical records of 367 patients who underwent PCNL by a single surgeon from January 2008 to December 2013 were reviewed retrospectively. All patients were divided into 3 Groups. Group-1 (n=232) included patients with no history of ipsilateral open stone surgery. Group 2 (n=86) patients had undergone one or more open stone surgeries before PCNL, patients with failed or recurrence following PCNL were placed in Group-3 (n=49). The demographic data, operation duration, stone free rate (SFR), number of attempts to access the collecting system and intra operative and postoperative complications between the three Groups were compared. RESULTS: There was no difference in sex, Body Mass Index (BMI), stone burden and laterality among the three Groups. Operation time was significantly less in first Group, while there was a statistically significant difference in operation duration between second and third Groups (p<0.05). The number of attempts to enter the collecting system was lower in the first Group in comparison to other two Groups (p<0.5). There was no significant differences among three groups in stone free rate. Intra operative and postoperative complications were slightly more frequent in Groups 2 and 3. Mortality occurred in 1 patient with colon perforation in Group-2. CONCLUSION: Our study demonstrated that PCNL can be performed in patients even as secondary procedure without further complications. PMID- 27256181 TI - Procalcitonin determined at emergency department as na early indicator of progression to septic shock in patient with sepsis associated with ureteral calculi. AB - INTRODUCTION: To investigate the role of initial procalcitonin (PCT) level as an early predictor of septic shock for the patient with sepsis induced by acute pyelonephritis (APN) secondary to ureteral calculi. MATERIALS AND METHODS: The data from 49 consecutive patients who met criteria of sepsis due to APN following ureteral stone were collected and divided into two groups: with (n=15) or without (n=34) septic shock. The clinical variables including PCT level for this outcome were retrospectively compared by univariate analysis, followed by multivariable logistic regression model. RESULTS: All subjects had hydronephrosis, and were hospitalized with the mean of 11.8 days (3-42 days). The mean size of the ureteral stones was 7.5mm (3-30mm), and 57% were located in upper ureter. At univariate analysis, patients with septic shock were significantly older, a higher proportion had hypertension, lower platelet count and serum albumin level, higher CRP and PCT level, and higher positive blood culture rate. Multivariate models indicated that lower platelet count and higher PCT level are independent risk factors (p=0.043 and 0.046, respectively). In ROC curve, the AUC was significantly wider in PCT (0.929), compared with the platelet count (0.822, p=0.004). At the cut-off of 0.52ng/mL, the sensitivity and specificity were 86.7% and 85.3%. CONCLUSION: Our study demonstrated elevated initial PCT levels as an early independente predictor to progress into septic shock in patients with sepsis associated with ureteral calculi. PMID- 27256182 TI - Laparoendoscopic single site surgery in pediatric urology: does it require specialized tools? AB - PURPOSE: To describe our experience utilizing Laparoendoscopic single site (LESS) surgery in pediatric urology. MATERIALS AND METHODS: Retrospective chart review was performed on LESS urologic procedures from November 2009 through March 2013. A total of 44 patients underwent 54 procedures including: nephrectomy (23), orchiopexy (14), varicocelectomy (9), orchiectomy (2), urachal cyst excision (3), and antegrade continence enema (3) (ACE). RESULTS: Median patient age was 6.9 years old. Estimated blood loss (EBL), ranged from less than 5cc to 47cc for a bilateral nephrectomy. Operative time varied from 56 mins for varicocelectomy to a median of 360 minutes for a bilateral nephroureterectomy. Incision length ranged between 2 and 2.5cm. In our initial experience we used a commercial port. However, as we progressed, we were able to perform the majority of our procedures via adjacent fascial punctures for instrumentation at the single incision site. One patient did require conversion to an open procedure as a result of bleeding. Three complications were noted (6.8%), with two Clavien Grade 3b complications. Two patients required additional procedures at 1-year follow-up. CONCLUSIONS: The use of LESS applies to many pediatric urologic procedures, ideally for ablative procedures or simple reconstructive efforts. The use of adjacent fascial puncture sites for instrumentation can obviate the need for a commercial port or multiple trocars. PMID- 27256183 TI - Open suprapubic versus retropubic prostatectomy in the treatment of benign prostatic hyperplasia during resident's learning curve: a randomized controlled trial. AB - PURPOSE: This study compared the suprapubic (SP) versus retropubic (RP) prostatectomy for the treatment of large prostates and evaluated perioperative surgical morbidity and improvement of urinary symptoms. MATERIALS AND METHODS: In this single centre, prospective, randomised study, 65 consecutive patients with LUTS and surgical indication with prostate volume greater than 75g underwent open prostatectomy to compare the RP (32 patients) versus SP (33 patients) technique. RESULTS: The SP group exhibited a higher incidence of complications (p=0.002). Regarding voiding pattern analysis (IPSS and flowmetry), both were significantly effective compared to pre-treatment baseline. The RP group parameters were significantly better, with higher peak urinary flow (SP: 16.77 versus RP: 23.03mL/s, p=0.008) and a trend of lower IPSS score (SP: 6.67 versus RP 4.14, p=0.06). In a subgroup evaluation of patients with prostate volumes larger than 100g, blood loss was lower in those undergoing SP prostatectomy (p=0.003). Patients with prostates smaller than 100g in the SP group exhibited a higher incidence of low grade late complications (p=0.004). CONCLUSIONS: The SP technique was related to a higher incidence of minor complications in the late postoperative period. High volume prostates were associated with increased bleeding when the RP technique was utilized. The RP prostatectomy was associated with higher peak urinary flow and a trend of a lower IPSS Score. PMID- 27256184 TI - Holmium laser enucleation of the prostate: surgical, functional, and quality-of life outcomes upon extended follow-up. AB - OBJECTIVES: To evaluate the long-term surgical, functional, and quality-of-life (QoL) outcomes after Holmium laser enucleation of the prostate (HoLEP) in patients with symptomatic benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We retrospectively reviewed recorded data on patients who underwent HoLEP between June 2002 and February 2005. Ninety-six patients were enrolled. Demographic, perioperative, and postoperative data were recorded. On follow-up, International Prostate Symptom Scores (IPSSs), prostate-specific antigen (PSA) levels, QoL scores, peak uroflowmetric data (Qmax values), and post-voiding residual urine volumes (PVR volumes), were recorded. Complications were scored using the Clavien system. Statistical significance was set at p<0.05. RESULTS: The mean follow-up time was 41.8+/-34.6 months and the mean patient age 73.2+/ 8.7 years. The mean prostate volume was 74.6+/-34.3mL. Significant improvements in Qmax values, QoL, and IPSSs and decreases in PSA levels and PVR volumes were noted during follow-up (all p values=0.001). The most common complication was a requirement for re-catheterisation because of urinary retention. Two patients had concomitant bladder tumours that did not invade the muscles. Eight patients (8.3%) required re-operations; three had residual adenoma, three urethral strictures, and two residual prostate tissue in the bladder. Stress incontinence occurred in one patient (1%). All complications were of Clavien Grade 3a. We noted no Clavien 3b, 4, or 5 complications during follow-up. CONCLUSIONS: HoLEP improved IPSSs, Qmax values, PVR volumes, and QoL and was associated with a low complication rate, during extended follow-up. Thus, HoLEP can be a viable option to transurethral resection of the prostate. PMID- 27256185 TI - Analysis of risk factors leading to postoperative urethral stricture and bladder neck contracture following transurethral resection of prostate. AB - PURPOSE: To determine risk factors of postoperative urethral stricture (US) and vesical neck contracture (BNC) after transurethral resection of prostate (TURP) from perioperative parameters. MATERIALS AND METHODS: 373 patients underwent TURP in a Chinese center for lower urinary tract symptoms suggestive of benign prostatic obstruction (LUTS/BPO), with their perioperative and follow-up clinical data being collected. Univariate analyses were used to determine variables which had correlation with the incidence of US and BNC before logistic regression being applied to find out independent risk factors. RESULTS: The median follow-up was 29.3 months with the incidence of US and BNC being 7.8% and 5.4% respectively. Resection speed, reduction in hemoglobin (DeltaHb) and hematocrit (DeltaHCT) levels, incidence of urethral mucosa rupture, re-catheterization and continuous infection had significant correlation with US, while PSA level, storage score, total prostate volume (TPV), transitional zone volume (TZV), transitional zone index (TZI), resection time and resected gland weight had significant correlation with BNC. Lower resection speed (OR=0.48), urethral mucosa rupture (OR=2.44) and continuous infection (OR=1.49) as well as higher storage score (OR=2.51) and lower TPV (OR=0.15) were found to be the independent risk factors of US and BNC respectively. CONCLUSIONS: Lower resection speed, intraoperative urethral mucosa rupture and postoperative continuous infection were associated with a higher risk of US while severer storage phase symptom and smaller prostate size were associated with a higher risk of BNC after TURP. PMID- 27256186 TI - Relationship between visual prostate score (VPSS) and maximum flow rate (Qmax) in men with urinary tract symptoms. AB - OBJECTIVE: To evaluate correlation between visual prostate score (VPSS) and maximum flow rate (Qmax) in men with lower urinary tract symptoms. MATERIAL AND METHODS: This is a cross sectional study conducted at a university Hospital. Sixty-seven adult male patients>50 years of age were enrolled in the study after signing an informed consent. Qmax and voided volume recorded at uroflowmetry graph and at the same time VPSS were assessed. The education level was assessed in various defined groups. Pearson correlation coefficient was computed for VPSS and Qmax. RESULTS: Mean age was 66.1+/-10.1 years (median 68). The mean voided volume on uroflowmetry was 268+/-160mL (median 208) and the mean Qmax was 9.6+/ 4.96mLs/sec (median 9.0). The mean VPSS score was 11.4+/-2.72 (11.0). In the univariate linear regression analysis there was strong negative (Pearson's) correlation between VPSS and Qmax (r=-848, p<0.001). In the multiple linear regression analyses there was a significant correlation between VPSS and Qmax (beta-http://www.blogapaixonadosporviagens.com.br/p/caribe.html after adjusting the effect of age, voided volume (V.V) and level of education. Multiple linear regression analysis done for independent variables and results showed that there was no significant correlation between the VPSS and independent factors including age (p=0.27), LOE (p=0.941) and V.V (p=0.082). CONCLUSION: There is a significant negative correlation between VPSS and Qmax. The VPSS can be used in lieu of IPSS score. Men even with limited educational background can complete VPSS without assistance. PMID- 27256187 TI - Assessing variability of the 24-hour pad weight test in men with post prostatectomy incontinence. AB - PURPOSE: Decision-making regarding surgery for post-prostatectomy incontinence (PPI) is challenging. The 24-hour pad weight test is commonly used to objectively quantify PPI. However, pad weight may vary based upon activity level. We aimed to quantify variability in pad weights based upon patient-reported activity. MATERIALS AND METHODS: 25 patients who underwent radical prostatectomy were prospectively enrolled. All patients demonstrated clinical stress urinary incontinence without clinical urgency urinary incontinence. On three consecutive alternating days, patients submitted 24-hour pad weights along with a short survey documenting activity level and number of pads used. RESULTS: Pad weights collected across the three days were well correlated to the individual (ICC 0.85 (95% CI 0.74-0.93), p<0.001). The mean difference between the minimum pad weight leakage and maximum leakage per patient was 133.4g (95% CI 80.4-186.5). The mean increase in 24-hour leakage for a one-point increase in self-reported activity level was 118.0g (95% CI 74.3-161.7, p<0.001). Pad weights also varied significantly when self-reported activity levels did not differ (mean difference 51.2g (95% CI 30.3-72.1), p<0.001). CONCLUSIONS: 24-hour pad weight leakage may vary significantly on different days of collection. This variation is more pronounced with changes in activity level. Taking into account patient activity level may enhance the predictive value of pad weight testing. PMID- 27256189 TI - Adult urethral stricture: practice of Turkish urologists. AB - OBJECTIVES: To evaluate national practice patterns in the treatment of male anterior urethral strictures among Turkish urologists. MATERIALS AND METHODS: A survey form including 12 questions prepared to determine active Turkish urologists' approach to diagnosis and treatment of the adult urethral stricture (US) were filled out. Based on the survey results, the institutions which 218 urologists work and their years of expertise, methods they used for diagnosis and treatment, whether or not they perform open urethroplasty and timing of open urethroplasty were investigated. RESULTS: Optic internal urethrotomy and dilatation are the most commonly used minimal invasive procedures in treatment of US with the ratios of 93.5% and 63.3% respectively. On the other hand it was seen that urethroplasty was a less commonly used procedure, compared to minimal invasive techniques, with the ratio of 36.7%. Survey results showed us that the number of US cases observed and open urethroplasty procedures performed increases with increasing years of professional experience. CONCLUSIONS: As a method demanding special surgical experience and known as a time-consuming and challenging procedure, open urethroplasty will be able to take a greater part in current urological practice with the help of theoretical education and practical courses given by specific centers and experienced authors. PMID- 27256188 TI - Can the success of structured therapy for giggle incontinence be predicted? AB - INTRODUCTION: To evaluate possible factors that can guide the clinician to predict potential cases refractoriness to medical treatment for giggle incontinence (GI) and to examine the effectiveness of different treatment modalities. MATERIAL AND METHODS: The data of 48 children referred to pediatric urology outpatient clinic between 2000 and 2013 diagnosed as GI were reviewed. Mean age, follow-up, GI frequency, associated symptoms, medical and family history were noted. Incontinence frequency differed between several per day to less than once weekly. Children were evaluated with uroflowmetry-electromyography and post-void residual urine. Clinical success was characterized as a full or partial response, or nonresponse as defined by the International Children's Continence Society. Univariate analysis was used to find potential factors including age, sex, familial history, GI frequency, treatment modality and dysfunctional voiding to predict children who would possibly not respond to treatment. RESULTS: Mean age of the patients was 8.4 years (range 5 to 16). Mean follow-up time and mean duration of asymptomatic period were noted as 6.7+/-1.4 years and 14.2+/-2.3 months respectively. While 12 patients were treated with only behavioral urotherapy (Group-1), 11 patients were treated with alpha adrenergic blockers and behavioral urotherapy (Group-2) and 18 patients with methylphenidate and behavioral urotherapy (Group-3). Giggle incontinence was refractory to eight children in-group 1; six children in-group 2 and eight children in-group 3. Daily GI frequency and dysfunctional voiding diagnosed on uroflowmetry-EMG were found as outstanding predictive factors for resistance to treatment modalities. CONCLUSIONS: A variety of therapies for GI have more than 50% failure rate and a standard treatment for GI has not been established. The use of medications to treat these patients would not be recommended, as they appear to add no benefit to symptoms and may introduce severe adverse effects. PMID- 27256190 TI - Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer? AB - PURPOSE: We investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low risk localized prostate cancer. MATERIALS AND METHODS: The data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded. RESULTS: In total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5-20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6-20.0) ng/mL in the PCa group (p=0.67). The PSA level was<=10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32). CONCLUSIONS: Our study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa. PMID- 27256191 TI - The long-term results of temporary urethral stent placement for the treatment of recurrent bulbar urethral stricture disease? AB - AIM: To evaluate the long term outcomes of temporary urethral stent placement for the treatment of recurrent bulbar urethral stricture. MATERIALS AND METHODS: Twenty-eight patients who underwent temporary polymer coated urethral stent placement due to recurrent bulbar urethral stricture between 2010 and 2014 were enrolled in the study. The long term outcomes of the patients were analyzed. RESULTS: The mean age of the patients was 62.3+/-6.4 (44-81). The overall clinical success was achieved in 18 (64.2%) of the 28 patients at a median (range) follow-up of 29 (7-46) months. No patient reported discomfort at the stent site. Stone formation was observed at the urethral stent implantation area only in one patient. Stenosis occurred in the distal end of the stents in two patients and took place in bulbar urethra in seven patients after removed the stents. The mean maximum urine flow rates were 6.24+/-2.81mL/sec and 19.12+/ 4.31mL/sec before and at 3 months after the procedure, respectively. CONCLUSION: In this study, the success rate of temporary urethral stent placement has remained at 64.2% at a median follow-up of 29 months. Therefore, our outcomes have not achieved desired success rate for the standard treatment of recurrent bulbar urethral stricture. PMID- 27256192 TI - Use and outcomes of amplatz renal dilator for treatment of urethral strictures. AB - INTRODUCTION: Urethral stricture disease is still a major problem in men. Many procedures are available for the treatment of urethral strictures; urethral dilatation is one of the oldest. The blind dilatation of urethral strictures may be a difficult and potentially dangerous procedure. The purpose of this study was to describe safe urethral dilatation using amplatz renal dilator and to report outcomes. MATERIALS AND METHODS: From 2010 to 2014, a total of 26 men with primary urethral strictures were managed by urethral dilatation using amplatz renal dilators. The parameters analyzed included presentation of patients, retrograde urethrography (RGU) findings, pre-and postoperative maximum flow rate (Qmax) on uroflowmetry (UF) and post-void residual urine (PVR). Patients were followed-up at 1.6 and 12 months. The technique described in this paper enables such strictures to be safely dilated after endoscopic placement of a suitable guidewire and stylet over which amplatz renal dilators are introduced. RESULTS: The mean age of the patients was 57.6 (35-72) years. The median stricture length was 0.82 (0.6-1.5)cm. Pre-operative uroflowmetry showed Qmax of 7.00 (4-12) mL/sec and ultrasonography showed PVR of 75.00 (45-195)mL. Postoperatively, Qmax improved to 18.00 (15-22)mL/sec (p<0.001) at 1 month, 17.00 (13-21)mL/sec (p<0.001) at 6 months and 15.00 (12-17)mL/sec (p<0.001) at 12 months. The post operative PVR values were 22.50 (10-60)mL (p<0.001), 30.00 (10-70)mL (p<0.001) and 30.00 (10-70) mL (p<0.001) at 1.6 12 months, respectively. The median procedure time was 15.00 (12-22) minutes. None of the patients had a recurrence during a 12-month period of follow-up. CONCLUSION: Urethral dilatation with amplatz renal dilators avoids the risks associated with blind dilatation techniques. This tecnique is a safe, easy, well-tolerated and cost-effective alternative for treatment of urethral strictures. PMID- 27256193 TI - Impact of body mass index, age and varicocele on reproductive hormone profile from elderly men. AB - OBJECTIVES: To study the impact of obesity, age and varicocele on sexual hormones of adult and elderly men. MATERIALS AND METHODS: 875 men who were screened for prostate cancer were enrolled in this study. Data recorded comprised age, body mass index (BMI), serum levels of total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicular stimulating hormone (FSH). Patients were divided in groups according to their BMI in underweight, normal weight, overweight and obese grades 1, 2 or 3. First, it was studied the association between age, BMI, and hormone profile. Then, clinical varicocele was evaluated in 298 patients to assess its correlation to the others parameters. RESULTS: Obese patients had lower levels of TT, FT and SHBG (p<0.001) compared to underweight or normal weight patients. There were no differences in age (p=0.113), FSH serum levels (p=0.863) and LH serum levels (p=0.218) between obese and non-obese patients. Obese grade 3 had lower levels of TT and FT compared to obese grade 1 and 2 (p<0.05). There was no difference in the SHBG levels (p=0.120) among obese patients. There was no association between varicocele and BMI; and varicocele did not impact on testosterone or SHBG levels. CONCLUSIONS: Men with higher BMI have a lower serum level of TT, FT and SHBG. The presence of clinical varicocele as well as its grade has no impact on hormone profile in elderly men. PMID- 27256194 TI - Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity. AB - OBJECTIVE: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. MATERIALS AND METHODS: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. RESULTS: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure >=20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. CONCLUSIONS: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients. PMID- 27256195 TI - Renal capsule for augmentation cystoplasty in canine model: a favorable biomaterial? AB - PURPOSE: To evaluate effectiveness of canine renal capsule for augmentation cystoplasty. MATERIALS AND METHODS: Ten adult dogs participated in this study. After induction of anesthesia each animal underwent bed side urodynamic study, bladder capacity and bladder pressure was recorded. Then via mid line incision abdominal cavity was entered, right kidney was identified and its capsule was dissected. Bladder augmentation was done by anastomosing the renal capsule to the bladder. After 6 months bed side urodynamic study was performed again and changes in bladder volume and pressure were recorded. Then the animals were sacrificed and the augmented bladders were sent for histopathology evaluation. RESULTS: Mean maximum anatomic bladder capacity before cystoplasty was 334.00+/-11.40cc which increased to 488.00+/-14.83cc post-operatively (p=0.039). Mean anatomic bladder pressure before cystoplasty was 19.00+/-1.58cmH2O which decreased to 12.60+/ 1.14cmH2O post-operatively (p=0.039). Histopathology evaluation revealed epithelialization of the renal capsule with urothelium without evidence of fibrosis, collagen deposits or contracture. CONCLUSIONS: Our data shows that renal capsule is a favorable biomaterial for bladder augmentation in a canine model. PMID- 27256196 TI - Recurring priapism may be a symptom of voiding dysfunction - case report and literature review. AB - Recurring priapism is rare in pre-pubertal children and may be attributed to multiple causes. We propose that voiding dysfunction (VD) may also justify this symptom and detail a clinical case of recurring stuttering priapism associated to overactive bladder that completely resolved after usage of anticholinergics and urotherapy. Sacral parasympathetic activity is responsible for detrusor contraction and for spontaneous erections and a relationship between erections and bladder status has been proved in healthy subjects (morning erections) and models of medullar trauma. High bladder pressures and/or volumes, voiding incoordination and posterior urethritis can potentially trigger reflex erections. PMID- 27256197 TI - Chromophobe renal cell carcinoma mimicking cortical invasion by synchronous invasive urothelial carcinoma of the intra-renal collecting system on CT urography. PMID- 27256198 TI - Intravesical human papillomavirus (IHPV) infection-endoscopic resection. PMID- 27256199 TI - RE: The value of testicular ultrasound in the prediction of the type and size of testicular tumors. PMID- 27256200 TI - RE: Efficacy of botulinum toxin type A 100 Units versus 200 units for treatment of refractory idiopathic overactive bladder. PMID- 27256201 TI - RE: An easy, reproducible and cost-effective method for andrologists to improve the laboratory diagnosis of nonobstructive azoospermia: a novel microcentrifugation technique. PMID- 27256202 TI - Use of pre-clinical surgically induced models to understand biomechanical and biological consequences of PTOA development. AB - Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injuries involving key stabilising structures such as the cruciate ligaments or the menisci. Both biomechanical and biological alterations that follow knee injuries have been implicated in PTOA development, although it has not been possible to differentiate clearly between the two causal factors. This review critically examines the outcomes from pre-clinical lapine and ovine injury models arising in the authors' laboratories and differing in severity of PTOA development and progression. Specifically, we focus on how varying severity of knee injuries influence the subsequent alterations in kinematics, kinetics, and biological outcomes. The immediate impact of injury on the lubrication capacity of the joint is examined in the context of its influence on biomechanical alterations, thus linking the biological changes to abnormal kinematics, leading to a focus on the potential areas for interventions to inhibit or prevent development of the disease. We believe that PTOA results from altered cartilage surface interactions where biological and biomechanical factors intersect, and mitigating acute joint inflammation may be critical to prolonging PTOA development. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:454-465, 2017. PMID- 27256203 TI - Applicability of the International Affective Picture System in Chinese older adults: A validation study. AB - The International Affective Picture System (IAPS) is a standardized tool widely used to induce emotions in psychological studies. The present study examined the reliability and validity of the IAPS in Chinese older adults. A sample consisting of 126 Chinese older adults (86 females; aged 67.3 +/- 4.96 years; 13.2 +/- 2.75 years of education) was recruited to rate valence and arousal for 942 IAPS pictures. The results showed a satisfactory reliability and validity of the IAPS among these participants. The reliability was supported by high internal consistency and low inter-individual variance of participants' ratings; the validity was supported by high similarities (in rating scores and in the distribution of the pictures in the valence-arousal affective space) and small differences (in mean ratings) between Chinese and German older adults. In conclusion, the study adds supportive evidence to the cross-cultural validity of the IAPS in older adults, and provides a set of normative emotional ratings that could be adopted as a criterion in the selection of emotional pictures in future studies engaging Chinese older adults. Comparison of the IAPS ratings across cultures and ages is also discussed. PMID- 27256205 TI - Prospective Evaluation of Continence Following Radical Cystectomy and Orthotopic Urinary Diversion Using a Validated Questionnaire. AB - PURPOSE: We evaluated continence outcomes in male patients undergoing orthotopic neobladder diversion after radical cystectomy using a validated questionnaire. MATERIALS AND METHODS: Using our institutional review board approved bladder cancer database we identified 1,269 patients who underwent open radical cystectomy from 2002 to 2015. Orthotopic neobladder was constructed in 935 (74%) patients, of whom 798 (85%) were male. Beginning in 2012 the patients completed a validated pictorial pad use questionnaire at each followup visit. The questionnaire assessed pad number, size and wetness as well as catheter use. Continence was defined as use of no pads or pads that are almost dry. Questionnaires were stratified into distinct postoperative intervals for analysis. Female patients, or patients with artificial urinary sphincters or prior radiotherapy were excluded from the study. RESULTS: A total of 188 male patients with available questionnaires were followed from September 2012 to August 2015. Overall 447 questionnaires were collected, with 351 interval distinct questionnaires separated into intervals of less than 3, 3 to 6, more than 6 to 12, more than 12 to 18, more than 18 to 36 and more than 36 months after surgery (64, 61, 58, 49, 61 and 58 questionnaires, respectively). Daytime continence increased from 59% at less than 3 months postoperatively to 92% by more than 12 to 18 months. Nighttime continence increased from 28% at less than 3 months postoperatively to 51% by more than 18 to 36 months. Nearly 50% of patients reported daytime and nighttime continence by 18 to 36 months. CONCLUSIONS: After orthotopic neobladder diversion in male patients, continence improves significantly by 6 months and subsequently plateaus with 92% daytime continence by more than 12 to 18 months. Orthotopic neobladder represents an excellent functional option for urinary diversion. PMID- 27256204 TI - Comparison of Pathological Outcomes for Men with Low Risk Prostate Cancer from Diverse Practice Settings: Similar Results from Immediate Prostatectomy or Initial Surveillance with Delayed Prostatectomy. AB - PURPOSE: We compared pathological outcomes after radical prostatectomy for a population based sample of men with low risk prostate cancer initially on active surveillance and undergoing delayed prostatectomy vs those treated with immediate surgery in order to better understand this expectant management approach outside of the context of academic cohorts. We hypothesized that delays in surgery due to initial surveillance would not impact surgical pathological outcomes. MATERIALS AND METHODS: We performed a prospective cohort study of 2 groups of patients with NCCN low risk prostate cancer from practices in the Michigan Urological Surgery Improvement Collaborative, that is 1) men who chose initial active surveillance and went on to delayed prostatectomy and 2) men who chose immediate prostatectomy. Diagnoses occurred from January 2011 through August 2015. For these 2 groups we compared radical prostatectomy Gleason scores, and rates of extraprostatic disease, positive surgical margins, seminal vesicle invasion and lymph node metastases. RESULTS: During a median followup of 506 days 79 (6%) of 1,359 low risk men choosing initial surveillance transitioned to prostatectomy. Compared to those treated with immediate prostatectomy (778), men undergoing delayed surgery were more likely to have Gleason score 7 or greater disease (69.2% vs 48.8%, respectively, p=0.004), but were no more likely to have positive margins, extraprostatic extension, seminal vesicle invasion or lymph node metastases. CONCLUSIONS: Patients with low risk prostate cancer who enter active surveillance have higher grade disease at prostatectomy compared to those undergoing immediate surgery. However, the lack of difference in other adverse pathological outcomes suggests preservation of the window of curability. PMID- 27256206 TI - Novel Biocompatible Adhesive for Intrarenal Embedding and Endoscopic Removal of Small Residual Fragments after Minimally Invasive Stone Treatment in an Ex Vivo Porcine Kidney Model: Initial Evaluation of a Prototype. AB - PURPOSE: Residual fragments related to endoscopic intracorporeal lithotripsy are a challenging problem. The impact of residual fragments remains a subject of discussion and growing evidence highlights that they have a central role in recurrent stone formation. Therefore, we developed a novel bioadhesive system for intrarenal embedding and retrieval of residual fragments after endoscopic lithotripsy in an ex vivo porcine kidney model. MATERIALS AND METHODS: In a standardized setting 30 human stone fragments 1 mm or less were inserted in the lower pole of an ex vivo porcine kidney model. We assessed the extraction efficacy of flexible ureteroscopy using the bioadhesive system in 15 preparations and a conventional retrieval basket in 15. Outcomes were compared regarding the endoscopic and macroscopic stone-free rate, and overall time of retrieval. RESULTS: Embedding and retrieving the residual fragment-bioadhesive complex were feasible in all trial runs. We observed no adverse effects such as adhesions between the adhesive and the renal collecting system or the instruments used. The stone-free rate was 100% and 60% in the bioadhesive and conventional retrieval groups, respectively (p = 0.017). Mean retrieval time was significantly shorter at 10 minutes 33 seconds vs 36 minutes 56 seconds in the bioadhesive group vs the conventional group (p = 0.001). CONCLUSIONS: This novel method involving adhesive based complete removal of residual fragments from the collecting system has proved to be feasible. Our evaluation in a porcine kidney model revealed that this technology performed well. Further tests, including inpatient studies, are required to thoroughly evaluate the benefit and potential drawbacks of bioadhesive based extraction of residual fragments after intracorporeal lithotripsy. PMID- 27256207 TI - Cardiac Disease-Induced Post-traumatic Stress Symptoms (CDI-PTSS) Among Patients' Partners. AB - It is well established that a patient's partner can be deeply affected by the traumatizing nature of the patient's illness. Yet, no study to date has focused on post-traumatic stress symptoms (PTSS) among partners of patients coping with an acute coronary syndrome (ACS). The current study's main aims were to address this gap and to evaluate cardiac disease-induced (CDI) PTSS prevalence in partners of patients who experienced ACS. Patients who experienced ACS and their partners were interviewed by telephone 2 to 6 months after patients' hospitalization. All patients and partners were screened for CDI-PTSS. Demographic and medical variables as well as partners' level of exposure to the cardiac event were assessed. Prevalence of CDI-PTSS was higher among partners than among patients. Partners' number of CDI-PTSS was not significantly associated with patients' number of CDI-PTSS or with any of the other explanatory factors measured, except for education level. The preliminary results that arose from the current study point to the vast number of individuals who must act as caregivers for their ill partners while having to cope with their own PTSS. Much effort should be channelled into integrating partners into cardiac recovery programmes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27256208 TI - Development and Implementation of Culturally Tailored Offline Mobile Health Surveys. AB - BACKGROUND: In low and middle income countries (LMICs), and other areas with low resources and unreliable access to the Internet, understanding the emerging best practices for the implementation of new mobile health (mHealth) technologies is needed for efficient and secure data management and for informing public health researchers. Innovations in mHealth technology can improve on previous methods, and dissemination of project development details and lessons learned during implementation are needed to provide lessons learned to stakeholders in both the United States and LMIC settings. OBJECTIVE: The aims of this paper are to share implementation strategies and lessons learned from the development and implementation stages of two survey research projects using offline mobile technology, and to inform and prepare public health researchers and practitioners to implement new mobile technologies in survey research projects in LMICs. METHODS: In 2015, two survey research projects were developed and piloted in Puerto Rico and pre-tested in Costa Rica to collect face-to-face data, get formative evaluation feedback, and to test the feasibility of an offline mobile data collection process. Fieldwork in each setting involved survey development, back translation with cultural tailoring, ethical review and approvals, data collector training, and piloting survey implementation on mobile tablets. RESULTS: Critical processes and workflows for survey research projects in low resource settings were identified and implemented. This included developing a secure mobile data platform tailored to each survey, establishing user accessibility, and training and eliciting feedback from data collectors and on site LMIC project partners. CONCLUSIONS: Formative and process evaluation strategies are necessary and useful for the development and implementation of survey research projects using emerging mHealth technologies in LMICs and other low resource settings. Lessons learned include: (1) plan institutional review board (IRB) approvals in multiple countries carefully to allow for development, implementation, and feedback, (2) in addition to testing the content of survey instruments, allow time and consideration for testing the use of novel mHealth technology (hardware and software), (3) incorporate training for and feedback from project staff, LMIC partner staff, and research participants, and (4) change methods accordingly, including content, as mHealth technology usage influences and is influenced by the content and structure of the survey instrument. Lessons learned from early phases of LMIC research projects using emerging mHealth technologies are critical for informing subsequent research methods and study designs. PMID- 27256209 TI - Valvular disease: Bivalirudin versus heparin for the treatment of cerebral embolization post-TAVR. PMID- 27256210 TI - Renal denervation for resistant hypertension: the wrong target? PMID- 27256212 TI - Genetics: Variants in ASGR1 linked to reduced CAD risk. PMID- 27256213 TI - Acute coronary syndromes: Use of antipsychotic drugs linked with risk of MI. PMID- 27256214 TI - Interventional cardiology: OSA predicts cardiac risk in patients undergoing PCI. PMID- 27256215 TI - Thermoelectric performance of restacked MoS2 nanosheets thin-film. AB - MoS2 has been predicted to be an excellent thermoelectric material due to its large intrinsic band gap and high carrier mobility. In this work, we exfoliated bulk MoS2 by the assistance of lithium intercalation and fabricated the restacked MoS2 thin-film using a simple filtration technique. These MoS2 thin-films with different thickness showed different thermoelectric performance. It was found that with the increase of thickness, carrier concentration, electrical conductivity and Seebeck coefficient all showed an increasing trend. In particular, the maximum Seebeck coefficient was able to reach 93.5 MUV K(-1). This high thermopower indicates that MoS2 will have ideal thermoelectric performance in the future through optimizing its structure. The highest figure of merit (ZT = 0.01) is calculated in this experiment. PMID- 27256211 TI - Acute coronary syndromes in women and men. AB - Evidence of sex-related disparities in the care and outcomes of patients with acute coronary syndrome (ACS) emerged >30 years ago, and yet the mechanisms behind these sex-specific differences remain unclear. In this Review, we discuss the current literature on differences between women and men in the clinical presentation, pathophysiology, evaluation, management, and outcomes of ACS. Although the symptoms of ACS and the benefits of therapy generally overlap between women and men, women continue to receive less-aggressive invasive and pharmacological therapy than men. In addition, young women in particular have worse short-term and long-term outcomes than men. To understand better the mechanisms behind these continued disparities, we have identified areas of future research that need to be urgently addressed in fields that range from clinical evaluation and management, to increasing representation of women in research. PMID- 27256216 TI - Impact of hyperventilation and apnea on myocardial oxygenation in patients with obstructive sleep apnea - An oxygenation-sensitive CMR study. AB - BACKGROUND: Oxygenation-sensitive cardiovascular magnetic resonance imaging (OS CMR) is an emerging technique that can monitor changes in myocardial oxygenation in vivo. Obstructive sleep apnea syndrome (OSAS) is associated with endothelial and microcirculatory dysfunction and increased cardiovascular morbidity and mortality. Little is known about myocardial responses to apnea in patients with OSAS. We hypothesized that the coronary vascular response to hyperventilation and long breath-hold is diminished in patients with OSAS when compared to healthy volunteers. METHODS: Twenty-nine OSAS patients and 36 healthy volunteers were prospectively enrolled. All CMR scans were performed on a clinical 3T system. Participants performed a breathing maneuver with 60s of hyperventilation followed by a maximal breath-hold. During the breath-hold, OS-CMR images were continuously acquired and signal intensity changes were measured by a blinded reader. RESULTS: Patients with OSAS were older than healthy volunteers (p<0.01) and presented more co-morbidities; 66% were currently treated with nocturnal positive airway pressure. Compared to healthy participants, the expected increase of myocardial oxygenation during the first 15s of the breath-hold was significantly lower in patients with OSAS (2.6+/-8.3% vs. 6.7+/-5.6%; p<0.05), and remained reduced at all time points during the breath-hold. Importantly this result was mainly driven by patients under continuous positive airway pressure (CPAP), suggesting that CPAP might have a greater impact on increase of myocardial oxygenation rather than OSAS itself. CONCLUSIONS: The myocardial vascular response to combined breathing maneuvers of hyperventilation followed by voluntary apnea is blunted in patients with obstructive sleep apnea. Clinical studies should now further define the clinical role of oxygenation-sensitive CMR in patients with respiratory disorders. PMID- 27256217 TI - Remnant lipoproteinemia predicts cardiovascular events in patients with type 2 diabetes and chronic kidney disease. AB - BACKGROUND: Patients having type 2 diabetes mellitus (DM) and chronic kidney disease (CKD) are at high risk of cardiovascular events. Triglyceride-rich lipoprotein levels are synergistically increased in patients with DM and CKD. This study examined the predictive value of remnant lipoprotein levels for cardiovascular events in patients with DM and CKD. METHODS: Three hundred and sixty-five patients with type 2 DM and CKD were enrolled. Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method. All patients were followed prospectively for a period of 45+/-23 months or until occurrence of one of the following events: cardiac death, non-fatal myocardial infarction, unstable angina requiring unplanned coronary revascularization, or ischemic stroke. RESULTS: During the follow-up period, 59 patients had cardiovascular events. Multivariate Cox analysis revealed that high levels of RLP-C (>=4.3mg/dL; median value) were a significant risk factor for cardiovascular events, independent of traditional risk factors (HR: 1.30; 95% CI: 1.04-1.63; p=0.02). The addition of high levels of RLP-C to traditional risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.36, p=0.01; and IDI 0.03, p=0.02). CONCLUSIONS: RLP-C is useful for risk assessment of future cardiovascular events in patients having type 2 DM and CKD. PMID- 27256218 TI - Role of echocardiography in patients with stroke. AB - Investigation of potential embolic source is an important diagnostic step in treating patients with ischemic stroke and transient ischemic attack. Cardiogenic embolism has been estimated to be the causative factor in 15-30% of all cases of ischemic stroke. Cardioembolic strokes are generally severe and recurrence and mortality rate high. Various cardiac disorders including atrial fibrillation, ventricular thrombus, valvular heart disease, cardiac tumors, and structural heart defects can cause cardioembolic stroke. Although the aortic arch is not a cardiac structure, it is usually considered under source of cardiac embolism (cardioaortic source) and is reviewed in this article. Echocardiography (both transthoracic and transesophageal) is a widely used and versatile technique that can provide comprehensive information of thromboembolic risk in patients with stroke. This article reviews potential cardiac sources of stroke and discusses the role of echocardiography in clinical practice. PMID- 27256219 TI - Predictors of short- and long-term mortality in hospitalized veterans with elevated troponin. AB - BACKGROUND: Cardiac troponin elevation is associated with mortality. We compared the mortality risk related to elevated troponin from acute coronary syndrome (ACS) and non-ACS causes in a hospitalized elderly veteran population. METHODS AND RESULTS: As part of a quality initiative at our Veterans Affairs hospital, all patients with elevated troponin were evaluated by a cardiologist to determine if ACS was present and to recommend management. We selected a sample (n = 761) of consecutive patients studied between February 2006 and February 2007 and examined all-cause mortality over extended follow-up. Nearly all were men (99.1%), and about half had coronary disease (n = 385, 50.5%) and diabetes (n = 339, 44.4%). ACS patients had lower mortality that non-ACS patients. Mortality began to diverge at 30 days; at 1 year it was 42.0% versus 29.0% (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.41-0.78) and at 6 years 77.7% versus 58.7% (OR: 0.41, 95% CI: 0.30-0.56). Cox regression models for mortality at multiple time points yielded several independent factors associated with mortality; however, the distribution of the factors was not sufficient to explain the observed difference in mortality. CONCLUSIONS: In this elderly, male veteran population, mortality related to an elevated troponin was higher at 1 and 6 years for non-ACS patients compared with ACS patients. Factors independently associated with a higher mortality risk were predominantly markers of general systemic illness, but did not elucidate the reasons why troponin elevation secondary to non-ACS causes carries this higher risk. A better understanding of these cardiac troponin elevations and implications for future mortality requires additional investigation. Journal of Hospital Medicine 2016;11:773-777. (c) 2016 Society of Hospital Medicine. PMID- 27256221 TI - Orally transmitted acute Chagas disease in domestic travelers in Colombia. PMID- 27256220 TI - Soluble antigen derived from IV larva of Angiostrongylus cantonensis promotes chitinase-like protein 3 (Chil3) expression induced by interleukin-13. AB - Angiostrongyliasis caused by Angiostrongylus cantonensis (A. cantonensis) is an emerging food-borne parasitic disease, which refers basically to eosinophilic meningitis. Chitinase-like protein 3 (Chil3), a member of chitinase-like protein family which has chemotactic activity for eosinophils, is reported to be highly upregulated in brain of mouse infected with A. cantonensis. The mechanisms of high expression of Chil3 and the association between A. cantonensis and Chil3 are rarely reported. In order to understand the mechanism of high expression of Chil3 in A. cantonensis-infected mouse, we measured the level of Chil3 in RAW 264.7 and BV2 cell lines stimulated with soluble antigen of A. cantonensis by qPCR and ELISA. To explore the role of Chil3 in inflammation caused by A. cantonensis, we extracted and cultured brain mononuclear cells (BMNCs) and detected the eosinophil chemotactic activity of Chil3 using transwell assay and flow cytometer. Furthermore, we treated the infected mice by injection with rmChil3 and then counted the number of larvae in brains of infected mice and treated mice to examine the association between the worm and Chil3. Our results showed the soluble antigen from A. cantonensis could promote the Chil3 expression in macrophage and microglial cell lines induced by interleukin-13. In conclusion, we supposed that high expression of Chil3 enhanced by soluble antigens from A. cantonensis might be the reason of serious eosinophil infiltration in mouse brain after A. cantonensis infection. PMID- 27256222 TI - William Arbuthnot Lane (1856-1943). PMID- 27256223 TI - [Efforts to improve the quality of neonatal screening, diagnosis and treatment of congenital adrenal hyperplasia]. PMID- 27256224 TI - [Consensus statement on neonatal screening for congenital adrenal hyperplasia]. PMID- 27256225 TI - [Expert consensus on the clinical application of chromosomal microarray analysis in pediatric genetic diseases]. PMID- 27256226 TI - [Characterization of ovarian adrenal rest tumors in children and adolescent females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency]. AB - OBJECTIVE: To summarize the characterization of ovarian adrenal rest tumors (OART) in children and adolescent females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). METHOD: We have diagnosed 4 cases of CAH 21-OHD with OART in the recent 5 years in pediatric endocrinology unit of the first affiliated hospital of Sun Yat-Sen University. Clinical characterizations were summarized, including symptoms, growth patterns and bone age advancements, serum steroid concentrations, imaging results and the follow-up data. RESULT: The 4 cases of OART accounted for 2.5 % of the CAH 21-OHD girls, which was much lower than the detection rate, 29.5%, of testicular ART in our patient group during the same period. The 4 cases included 3 salt wasters and 1 with simple virilizm. OART were diagnosed at the age of 8.9 years, 15.8 years, 21.4 years and 9.3 years, respectively. Before the diagnosis of OART, their daily hydrocortisone doses reached 16 mg/(m(2).d)to 24 mg/(m(2).d). The patients presented with deteriorated acne, deepened voice, amenorrhea (2 cases), accelerated growth and advanced bone age, DeltaBA/DeltaCA reached 1.2(during GnRHa treatment)and 2.0. Their serum adrenal steroids increased significantly and hyperplasia of adrenal glands were found in all patients. The diagnosis could be confirmed before the operation in only 1 case. The diagnosis could not be made until the planned sub-total adrenalectomy in the other 3 cases. The follow-up periods of OART were 4.8, 4.7, 3.8 and 2.7 years, respectively. Removal of OART resulted in symptoms relief at least partialy and lowered daily hydrocortisone doses, 14 to 19 mg/(m(2).d). CONCLUSION: The detection rate of OART was much lower than testicular ART. Before the diagnosis of OART, the patients presented with deteriorated virilescence, accelerated growth and advanced bone age, elevated serum adrenal steroids and hyperplasia of adrenal glands. Removal of the OART resulted in symptoms relief at least partialy. PMID- 27256227 TI - [Blood 7-ketocholesterol level, clinical features and gene mutation analysis of 18 children with Niemann-Pick disease type C]. AB - OBJECTIVE: To investigate 7-ketocholesterol (7-KC) level in the blood, clinical features and gene mutation of Niemann-Pick disease type C (NPC). METHOD: Eighteen patients diagnosed as NPC in Shanghai Xinhua Hospital seen from February 2013 to October 2014 were enrolled in this study. They included 13 males and 5 females and aged from 5 months to 21 years. The plasma 7-KC concentrations, clinical features and gene mutations of NPC patients were reviewed retrospectively. RESULT: Fourteen NPC patients had neurological symptoms with the age of neurological onset from 1 year to 16 years. In seven cases the disease was early infantile subtype, in 1 late-infantile subtype, in five juvenile subtype and in one adult subtype. The 7-KC value in the plasma of NPC patients was higher than the normal range, (348.5+/-168.7) MUg/L in the early-infantile subtype, 150.6 MUg/L in the late-infantile subtype, (145.0+/-46.3) MUg/L in the juvenile subtype, and 32.0 MUg/L in the adult subtype, respectively, additionally, four NPC patients had no observable neuropsychiatric disability when confirmed to be NPC by genetic testing, with the plasma 7-KC value (345.6+/-134.2) MUg/L; 16 of 18 patients had splenomegaly or hepatosplenomegaly. Among 18 patients, 34 different mutations in the NPC1 gene were identified including 27 reported mutations, 1 novel small deletion 3609_3610delAC, five novel exonic point mutations, c. 3683T>C(M1228T), c. 3679A>T(R1227W), c. 1070C>T(S357L), c. 1456A>C(N486H) and c. 1142G>A(W381X) and 1 novel intronic mutation c. 881+ 3A>G. CONCLUSION: The 7-KC levels in the blood of patient was remarkably increased, and there was a tendency that 7-KC levels inversely correlated with the age of neurological onset. Most NPC patient had splenomegaly or hepatosplenomegaly. Among 18 patients, 34 different mutations in the NPC1 gene were identified including seven novel mutations, which enriched the gene mutation spectrum. PMID- 27256228 TI - [Rapamycin in the treatment of cardiac rhabdomyoma associated with tuberous sclerosis complex]. AB - OBJECTIVE: To assess the efficacy and safety of mammalian target of rapamycin (mTOR) inhibitor rapamycin in treatment of children with cardiac rhabdomyoma, associated with tuberous sclerosis complex (TSC). METHOD: The clinical data of children with cardiac rhabdomyomas, who had received a diagnosis of TSC previously, were collected between September 2011 and November 2015 from Pediatric Department of the People's Liberation Army General Hospital.Patients in line with the inclusion criteria received long-term treatment with sirolimus.The starting doses of sirolimus was 1 mg/ (m(2).d), and the plasma concentration was maintained at 5-10 MUg/L.The size and number of cardiac rhabdomyomas were analyzed after treatment with rapamycin, and the efficacy and safety were assessed. The Wilcoxon test was used to analyze data. RESULT: All the 51 children met the inclusion and exclusion criteria, including 30 males and 21 females.The median age for rapamycin treatment was 15.0 months (7.0-35.0 months). Tumors disappeared in 26 (51%) children, decreased by more than 50%(including 50%) in 15 (29%) children, decreased by less than 50% in 5 (12%) children, and had no change or progressed in 4 (8%) children.The number of tumors decreased by 77(72%). The median maximum diameter of tumor was 8.7 (5.9-11.3) mm before treatment, 0.0 (0.0 4.0) mm after treatment, and the median decrease of tumor size were 6.7 (3.9 10.0) mm (Z=-8.817, P<0.01). The median disappearance time was 3.26 (2.92-5.37) months.Among different age groups, after treatment by rapamycin, the rate of tumor's disappearance was 50% (12/24) in 0-1 years group.Tumors disappeared in 10 of 16 patients in >1-3 years group and in 4 of 11 patients in >3 years group.The rate of tumor's disappearance was the highest after 3 months of treatment as compared with 6 and 12 months of treatment.Ten children had adverse event that was related to rapamycin.Canker sore was reported in one child and dyslipidemia was reported in 9 children. CONCLUSION: Rapamycin is efficacious and well tolerate in treatment of cardiac rhabdomyomas associate with TSC, and lead to a reduction in tumor size and number, in addition, significantly shorten the duration of cardiac rhabdomyoma. PMID- 27256229 TI - [Partial thyroxine binding globulin deficiency in test tube infants: report of cases and literature review]. AB - OBJECTIVE: To investigate the clinical characteristics of twins with thyroxine binding globulin (TBG) deficiency and to find SERPINA7 gene mutations. METHOD: Data(2015) related to clinical characteristics, serum biochemistry, gene mutations and pedigree of two children with TBG deficiency were collected in the First Affiliated Hospital of College of Medicine, Zhejiang University. The related literature was searched form China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center for Biotechnology Information and PubMed (up to December 2015) by using search terms "Thyroxine binding globulin deficiency, gene, mutation" . RESULT: Both patients were diagnosed as central hypothyroidism at the beginning and treated with L thyroxine. Both of the identical twins of the triplet were observed for mutation in exon3, c. 631G>A(p.A211T), a new mutation had not been reported, but their parents and another non-identical triplet brother were normal. Literature review showed that 23 foreign cases with SERPINA7 gene mutation had been reported, however, no Chinese with SERPINA7 gene mutation had been reported. Among reported cases it was shown that SERPINA7 gene mutations located in exon, intron, promoter and enhancer. Up to now, 49 variants had been identified, 41 of them located in the mutated genes. Including these two cases, patients with thyroxine binding globulin deficiency were characterized by reduced serum TH levels, but normal free TH and TSH and absence of clinical manifestations. CONCLUSION: The new mutation of SERPINA7 gene c. 631G>A(p.A211T)is not transmitted via the known X chromosome linked heredity, and as the cases were test tube triplet infants, it is a de novo mutation. The serum thyroid function tests of TBG deficiency showed decreased TT4, TT3 and normal TSH and TBG deficiency is often misdiagnosed as central hypothyroidism. PMID- 27256230 TI - [Genetic analysis for 5 congenital hypothyroidism patients due to dyshormonogenesis]. AB - OBJECTIVE: To analyze molecular characteristics of 5 congenital hypothyroidism (CH) patients due to dyshormonogenesis. METHOD: We enrolled 5 CH patients due to dyshormonogenesis who were identified in Newborn Screening Center of Guangxi Zhuang Autonomous Region, China. Blood samples were collected from the patients and their parents, and genomic DNA was extracted from peripheral blood leukocytes. All exons of DUOX2, TG, TPO and NIS gene together with their exon intron boundaries were screened by next-generation sequencing. Specimens from 100 normal controls were tested for these novel variations. RESULT: No TPO, NIS or TG gene mutations were identified. Direct sequencing of the DUOX2 gene revealed that patient 1 had a compound heterozygote for c. 3340delC and p. R683L, patient 2 was homozygous for p. K530X and patient 3 was a heterozygote for p. E879K. Both biallelic and monoallelic heterozygous mutations in DUOX2 were associated with transient CH. Novel mutations included c. 3340delC and p. R683L, analysis of 100 healthy subjects without thyroid disease did not show the same change. CONCLUSION: Genetic analysis of TPO, NIS, DUOX2 and TG gene in 5 unrelated CH patients with thyroid dyshormonogenesis revealed two novel DUOX2 mutations, both were biallelic and monoallelic heterozygous mutations in DUOX2 associated with transient CH. PMID- 27256231 TI - [Applying multiplex ligation-dependent probe amplification in the diagnosis of 5 cases with ornithine transcarbamylase deficiency]. AB - OBJECTIVE: To detect large genomic deletions or duplications of ornithine transcarbamylase (OTC) gene by multiplex ligation-dependent probe amplification (MLPA). METHOD: Thirty cases of suspected OTC deficiency (OTCD) patients based on tandem-mass spectrum results were recruited in Xinhua Hospital from 2012 to 2014, among whom 13 were male and 17 were female. Sanger sequencing of OTC gene revealed mutations in 23 cases. MLPA was performed in the patients whose previous Sanger sequencing failed to detect any disease-causing mutation. The samples were treated via the steps of DNA degeneration, the probe hybridization, connecting the hybridization probe, PCR amplification and capillary electrophoresis. The data were analyzed using Coffalyser software. RESULT: Abnormal MLPA results were found in 5 patients without mutation detected in previous Sanger sequencing. Patient 1, a 9-year old girl, had a heterozygous deletion of Exon 2-4. Patient 2, a male newborn, died 10 days after birth. The examination of the mother's sample by MLPA revealed a heterozygous duplication of exon 2-6. Patient 3, a 10-day old boy, was found to harbor a hemizygous deletion of exon 7-10. Patient 4, a 2-year old girl, harbored a heterozygous deletion of exon 1-4. The fifth patient died at the age of 6 years, and his mother carried a heterozygous duplication of exon 1 4. CONCLUSION: MLPA can be helpful in detecting the OTC gene defects, particularly for OTCD patients without mutation detected by Sanger sequencing. PMID- 27256232 TI - [Target gene sequence capture and next generation sequencing technology to diagnose four children with Alagille syndrome]. AB - OBJECTIVE: To make genetic diagnosis of Alagille syndrome (ALGS) patients using target gene sequence capture and next generation sequencing technology. METHOD: Target gene sequence capture and next generation sequencing were used to detect ALGS gene of 4 patients. They were hospitalized at the Affiliated Hospital, Capital Institute of Pediatrics between January 2014 and December 2015, referred to clinical diagnosis of ALGS typical and atypical respectively in 2 cases. Blood samples were collected from patients and their parents and genomic DNA was extracted from lymphocytes. Target gene sequence capture and next generation sequencing was detected. Sanger sequencing was used to confirm the results of the patients and their parents. RESULT: Cholestasis, heart defects, inverted triangular face and butterfly vertebrae were presented as main clinical features in 4 male patients. The first hospital visiting ages ranged from 3 months and 14 days to 3 years and 1 month. The age of onset ranged from 3 days to 42 days (median 23 days). According to the clinical diagnostic criteria of ALGS, patient 1 and patient 2 were considered as typical ALGS. The other 2 patients were considered as atypical ALGS. Four Jagged 1(JAG1) pathogenic mutations were detected. Three different missense mutations were detected in patient 1 to patient 3 with ALGS(c.839C>T(p.W280X), c. 703G>A(p.R235X), c. 1720C>T(p.V574M)). The JAG1 mutation of patient 3 was first reported. Patient 4 had one novel insertion mutation (c.1779_1780insA(p.Ile594AsnfsTer23)). Parental analysis verified that the JAG1 missense mutation of 3 patients were de novo. The results of sanger sequencing was consistent with the results of the next generation sequencing. CONCLUSION: Target gene sequence capture combined with next generation sequencing can detect two pathogenic genes in ALGS and test genes of other related diseases in infantile cholestatic diseases simultaneously and presents a high throughput, high efficiency and low cost. It may provide molecular diagnosis and treatment for clinicians with good clinical application prospects. PMID- 27256233 TI - [The value of brain magnetic resonance imaging in the early diagnosis of neuropsychiatric systemic lupus erythematosus]. AB - OBJECTIVE: To investigate the value of brain magnetic resonance imaging (MRI) in evaluating the intracranial injuries in patients with juvenile onset systemic lupus erythematosus (SLE). METHOD: Data of brain MRI, CT, electroencephalogram (EEG), cerebrospinal fluids analysis and clinical features of the central nervous system of 44 patients from March 2007 to March 2015 with juvenile onset SLE who were not treated with glucocorticoids (Gcs) and immunosuppressive agents (Is) were retrospectively analyzed and compared. RESULT: Twenty-seven out of 44 patients demonstrated abnormal signs on brain MRI, including encephalatrophy, cerebral infarction, demyelination, encephalorrhagia, vertebral arteriostenosis and abnormal signals on the brain diffusion-weighted imaging (DWI). Sixteen patients had clinical features of the central nervous system involvement, fifteen had continuous headache, nine had continuous dizziness, seven had convulsions, three had hemiplegia, one had blurred vision. Physical examination of the nervous system: ten patients had abnormal signs, all had cervical rigidity, five showed pyramidal sign, three showed loss of muscle tone, two with cranial neuropathies and one had paresthesia. EEG: Ten patients showed abnormal waves on EEG, all showed diffused slow-waves, and five showed sharp waves and spikes. Cerebrospinal fluids analysis: six patients had abnormal results, five of them had cell count elevation and one had cell count and protein elevation, while there was glucose and chloride degression. Brain CT: Eight patients received CT scan, two showed cerebral infarction. chi(2) test was used to compare the differences among head MRI, EEG, cerebrospinal fluid analysis, physical examination of the nervous system, clinical features of the nervous system, the difference was significant(chi(2)=12.055, P=0.001; chi(2)=19.627, P=0.001; chi(2)=3.859, P=0.049; chi(2)=12.055, P=0.001). CONCLUSION: Brain MRI may be a better method in early diagnosis of intracranial injuries than CT, EEG, cerebrospinal fluid analysis and physical examination of the nervous system. Patients with juvenile onset SLE should receive brain MRI after diagnosis in order to investigate the intracranial injuries. Abnormal signals on the DWI are the signs of active disease. PMID- 27256234 TI - [Clinical application of AMPLATZER Vascular Plug II in transcatheter closure of congenital coronary artery fistula in children]. AB - OBJECTIVE: To evaluate the feasibility of applying AMPLATZER Vascular Plug II (AVP II) in transcatheter closure of congenital coronary artery fistula in children. METHOD: Transcatheter closure procedure applying AVP II was carried out in 7 patients (3 males and 4 females, age 1.2-12.0 years) with congenital coronary artery fistula between May 2014 and September 2015 in Pediatric Cardiology Department of Guangdong Cardiovascular Institute. Selective coronary artery angiography and aortic root angiography were performed after the release of the device to evaluate the immediate therapeutic effect. Echocardiography and electrocardiography were performed at 1 day, 1 month, 3 months, 6 months, 1 year post procedure and repeated once a year during the follow-up period. RESULT: Transcatheter deployment of the device was successfully accomplished in all patients. The narrowest diameter of the fistula was (8.6+/-2.8) mm (4.0-12.5 mm), and the size of the deployed device ranged from 10.0 to 16.0 mm. Immediate selective coronary artery angiography revealed no residual shunt in 5 patients and trivial residual shunt in 2 patients. During a mean follow-up period of 2.7 (1.0-16.0) months, echocardiography showed that 3 patients remained no residual shunt, while 2 patients had trivial residual shunt, 2 patients developed small residual shunt. Cardiac murmur disappeared post procedure in all patients. Electrocardiography showed no ST-T changes. No migration or detachment of the device was found. CONCLUSION: AVP II is a safe and effective choice in transcatheter closure of congenital coronary artery fistula in children. PMID- 27256235 TI - [Outcome of childhood T-cell acute lymphoblastic leukemia: a report of 99 cases]. AB - OBJECTIVE: To explore the incidence, clinical characteristics and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL) enrolled in protocol ALL 2005. METHOD: Retrospective reviews of patients diagnosed as having T-ALL were studied in the period between May 2005 and August 2013 in Shanghai Children's Medical Center. Predictive values of early treatment responses, including prednisone response, bone marrow morphology on day 35 during induction chemotherapy, and minimal residual disease (MRD) monitored by flow cytometry on day 35 and 55, were analyzed. The Kaplan-Meier method was used to assess the survival rates. RESULT: Ninety-nine evaluable patients aged 1-18 years with newly diagnosed T-ALL were enrolled in protocol ALL-2005. The median follow-up period for patients remaining alive in continuous remission was 60 months (24-109 months). The 5-year event free survival (EFS) and overall survival (OS) rates for these patients were 65% and 69%, respectively. Forty-three (43%) patients were older than 10 years at diagnosis. A total of 61 patients presented with initial white blood cell count (WBC)>=50*10(9)/L. Thirty-seven patients with mediastinal mass were found in this study. Seventy-one patients were defined as prednisone good responders (PGR) on day 8 of prednisone therapy. Ninty-four patients achieved complete remission (CR) on day 35 of induction therapy. MRD negative status (<0.01%) on day 35 were seen in 55% of the 42 assessed patients. MRD negative status on day 55 was seen in 78% of the 52 assessed patients. Patients with high MRD (>1%) on day 55 5-year EFS was 40% were associated with poor prognosis (P=0.03). Early T-cell precursor (ETP) subtype was not associated with treatment outcome in this study. Six patients abandoned therapy, 10 lost to follow-up, 22 had relapsed disease, 1 was diagnosed as having a second tumor and 20 patients died. CONCLUSION: Overall outcome for T-ALL on protocol ALL-2005 is favorable. MRD results on day 55 of induction therapy have important prognostic and therapeutic implications. PMID- 27256236 TI - [Novel SCN5A mutation leading either to progressive cardiac conduction defect or Brugada syndrome in a family]. PMID- 27256237 TI - [Four cases of central venous catheter-related effusions in premature infants]. PMID- 27256238 TI - [Report of a case with pulmonary infection of Lophomonas blattarum in children]. PMID- 27256239 TI - [A case of Kawasaki disease with autoimmune hemolytic anemia]. PMID- 27256240 TI - [Pratt speech analytic software in diagnosing myasthenia gravis presenting with dysphonia as the initial symptom, a case report]. PMID- 27256241 TI - [A case of primitive myxoid mesenchymal tumor of infancy with ascites as the initial symptom]. PMID- 27256243 TI - [Neurally adjusted ventilatory assistance in neonates: progress in research and application]. PMID- 27256242 TI - [Progress of epilepsy and mental retardation limited to females]. PMID- 27256244 TI - [Research progress in ganglioside GD2 as target for cellular immunotherapy of neuroblastoma]. PMID- 27256245 TI - [Clinical pharmacology session of the twentieth national pediatric academic conference of the Chinese Medical ssociation and the sixth national pediatric clinical pharmacology academic conference]. PMID- 27256246 TI - Predicting the outcomes for out-of-hospital cardiac arrest patients using multiple biomarkers and suspension microarray assays. AB - Predicting the prognosis for cardiac arrest is still challenging. Combining biomarkers from diverse pathophysiological pathways may provide reliable indicators for the severity of injury and predictors of long-term outcomes. We investigated the feasibility of using a multimarker strategy with key independent biomarkers to improve the prediction of outcomes in cardiac arrest. Adult out-of hospital cardiac arrest patients with sustained return of spontaneous circulation were prospectively enrolled in this study. Blood samples were taken at 2 and 24 hours after cardiac arrest. Suspension microarray assays were used to test 21 different biomarkers. A total of 99 patients were enrolled, 45 of whom survived to hospital discharge. We identified 11 biomarkers that, when combined with clinical variables and factors of APACHE II score and history of arrhythmia, were independent determinants for outcome of in-hospital mortality (concordance = 0.9249, standard error = 0.0779). Three biomarkers combined with APACHE II and age were independent determinants for favorable neurological outcome at hospital discharge (area under the receiver-operator characteristic curve, 0.938; 95% confidence interval, 0.854 ~ 1.0). In conclusion, a systemic multiple biomarker approach using suspension microarray assays can identify independent predictors and model the outcomes of cardiac arrest patients during the post-cardiac arrest period. PMID- 27256247 TI - Microcomputed tomographic evaluation of canal transportation and centring ability of ProTaper Next and Twisted File Adaptive systems. AB - AIM: To evaluate canal transportation and centring ability of ProTaper Next (PTN) and Twisted File Adaptive (TFA) systems using microcomputed tomographic (micro CT) imaging. METHODOLOGY: Twenty isthmus-containing mesial roots of mandibular molars were anatomically matched based on similar morphological dimensions using micro-CT evaluation (resolution of 14.25 MUm) and assigned to two experimental groups (n = 10) according to the system used for root canal preparation: PTN and TFA groups. Then, the specimens were scanned again and the matched images of the mesial canals, before and after preparation, were examined at three cross-section levels (3, 5 and 7 mm from the apical end of the root) to analyse canal transportation and centring ratio. Independent-samples t-test was used to compare canal transportation and centring ratio between the groups. All statistical procedures were performed with a significance level set at 5%. RESULTS: Root canals prepared with either PTN or TFA systems had similar canal transportation and centring ratios at all levels (P > 0.05). CONCLUSION: PTN and TFA had similar results regarding canal transportation and centring ability. PMID- 27256248 TI - Bacteremia due to Cellulosimicrobium cellulans associated with central catheter for hemodialysis. PMID- 27256249 TI - Primary sternal osteomyelitis caused by Salmonella enteritidis. PMID- 27256250 TI - Systematic review of qualitative studies exploring parental experiences in the Neonatal Intensive Care Unit. AB - AIMS AND OBJECTIVES: To determine the feasibility and utility of a thematic analysis approach to synthesising qualitative evidence about parental experiences in the neonatal intensive care unit. BACKGROUND: Admission of infants to the neonatal intensive care unit is usually an unexpected event for parents who can cause them to experience psychosocial difficulties. A qualitative systematic review is the best method for exploring these parents' experiences regarding this type of admission. DESIGN: Systematic review. METHODS: Qualitative studies in peer-reviewed journals aimed at understanding parental experiences regarding infant neonatal intensive care unit admission were identified in six electronic databases. Three reviewers selected relevant articles and assessed the quality of the methodological studies using the Critical Appraisal Skills Programme. A thematic analysis approach was used to identify the most common themes in the studies describing parental experiences in the neonatal intensive care unit. RESULTS: A total of eighty articles were identified; nine studies were included in this review. Four studies used semistructured interviews, three used interviews, one used self-reporting and one used both focus group and interview methodologies. Common themes across parents' experiences were the stress of hospitalisation, alteration in parenting roles and the impact of infant hospitalisation on psychological health. CONCLUSION: Having an infant hospitalised in the neonatal intensive care unit is a stressful experience for parents. This experience is the result of exposure to different stressors related to the infant's condition, an alteration in parenting roles or the neonatal intensive care unit environment and staffing. These parents suffered negative psychological effects, experienced an interrupted development of a healthy parent infant attachment and/or felt parental role alteration. RELEVANCE TO CLINICAL PRACTICE: The study's findings are crucial for neonatal intensive care unit nurses to develop intervention strategies and programmes that help parents to decrease the stress of their experience and to support them in facing this stressful situation. PMID- 27256260 TI - Veterinary anthropology explored. AB - Veterinary and social scientists came together at the Centre for Medical Anthropology at the University of Edinburgh in April to discuss areas of common interest and the possibility of defining a new interdisciplinary field of 'veterinary anthropology'. Andrew Gardiner, one of the organisers of the international meeting, reports. PMID- 27256252 TI - Natural history and risk stratification of patients undergoing non-invasive ventilation in a non-ICU setting for severe COPD exacerbations. AB - Non-invasive ventilation (NIV) delivered in an intensive care unit (ICU) has become the cornerstone in the treatment of patients with severe chronic obstructive pulmonary disease (COPD) exacerbations. A trend towards managing these patients in non-ICU setting has emerged in recent years, although out-of hospital survival by this approach and how to prognosticate it is unknown. We aimed to investigate these issues. We consecutively recruited 100 patients (49 males; median age 82 years) who received NIV treatment for acute respiratory failure due to COPD exacerbation in non-ICU medical wards of our hospital, between November 2008 and July 2012. We assessed survival (both in-hospital and out-of-hospital) of all these patients, and analyzed baseline parameters in a Cox proportional hazards model to develop a prognostic score. The median survival in the study population was 383 days (240-980). Overall survival rates were 71.0, 65.3, and 52.7 % at 1, 3, and 12 months, respectively. Age >85 years, a history of heart disorders and a neutrophil count >=10 * 10(9) were associated with higher mortality at Cox's analysis (chi (2) = 35.766, p = 0.0001), and were used to build a prognostic score (NC85). The presence of two or more factors determined the deepest drop in survival (when NC85 >=2, mortality at 1, 3, and 12 was 60.7, 70.4, and 77.2 %, respectively, while when NC85 = 0 were 4.0, 4.0, and 14.0 %). A simple model, based on three variables (age, neutrophil count and history of heart disease), accurately predicts survival of COPD patients receiving NIV in a non-ICU setting. PMID- 27256251 TI - Functional characterization of ABCB4 mutations found in progressive familial intrahepatic cholestasis type 3. AB - Multidrug resistance 3 (MDR3), encoded by the ATP-binding cassette, subfamily B, member 4 gene (ABCB4), localizes to the canalicular membrane of hepatocytes and translocates phosphatidylcholine from the inner leaflet to the outer leaflet of the canalicular membrane. Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare hepatic disease caused by genetic mutations of ABCB4. In this study, we characterized 8 ABCB4 mutations found in PFIC3 patients, using in vitro molecular assays. First, we examined the transport activity of each mutant by measuring its ATPase activity using paclitaxel or phosphatidylcholine. Then, the pathogenic mechanisms by which these mutations affect MDR3 were examined through immunoblotting, cell surface biotinylation, and immunofluorescence. As a result, three ABCB4 mutants showed significantly reduced transport activity. Among these mutants, one mutation A364V, located in intracellular domains, markedly decreased MDR3 expression on the plasma membrane, while the others did not affect the expression. The expression of MDR3 on the plasma membrane and transport activity of A364V was rescued by a pharmacological chaperone, cyclosporin A. Our study provides the molecular mechanisms of ABCB4 mutations and may contribute to the understanding of PFIC3 pathogenesis and the development of a mutation-specific targeted treatment for PFIC3. PMID- 27256261 TI - Misplaced batteries result in lead poisoning in suckler cows. AB - Lead poisoning in suckler herdsBovine abortion associated with spoiled or contaminated feedListerial meningoencephalitis in ewesProliferative haemorrhagic enteropathy in pigsPoxvirus infection in a bantam These are among matters discussed in the disease surveillance report for February 2016 from SAC Consulting: Veterinary Services (SAC C VS). PMID- 27256262 TI - Regional limb perfusion in horses. PMID- 27256263 TI - Monensin toxicity in dogs. PMID- 27256264 TI - What could 'Brexit' mean for vets? AB - BVA has produced a briefing paper on the possible implications of a British exit from the EU and is inviting vets to have their say via the BVA community, explains BVA policy offer Susie Child. PMID- 27256266 TI - JAB campaign needs farm vets. AB - A coalition of stakeholders is working to raise awareness of the risks of bluetongue and BVA is encouraging farm vets to get involved. PMID- 27256267 TI - BVA welcomes report on tackling drug-resistant infections. AB - BVA recognises the continuing need to show leadership in tackling antimicrobial resistance, as Hannah Jordan, BVA policy officer, explains. PMID- 27256268 TI - 'The best CPD I have done in a while'. AB - The BVA IN PRACTICE: CPD offering is going from strength to strength, says Tim Keen, BVA marketing manager, and the programme for July to December 2016 is now available. PMID- 27256269 TI - BVA marks its patron's birthday. AB - Along with the rest of the nation, BVA is celebrating Queen Elizabeth II's 90th birthday. President Sean Wensley explains how BVA will mark the occasion and looks back to her visit to the Association's headquarters in its centenary year. PMID- 27256270 TI - BVA Gala Dinner - a date for your diary. AB - BVA's 2016 Gala Dinner will be held at the London Marriott Hotel West India Quay on November 17. Here Tim Keen, BVA marketing manager, explains what the evening will involve. PMID- 27256271 TI - New debt recovery service provider. AB - Laura Carleton, member services officer, announces BVA's link with a new provider of debt recovery services. PMID- 27256272 TI - The power of social media. AB - Nicky Mansell, one of the recent graduate representatives on BVA Council, looks at some of the pros and cons of social media. PMID- 27256273 TI - Academia or practice? AB - Amy Barstow's friends and family always knew she was destined for veterinary medicine. Her aim initially was clinical practice; however, an interest in equine lameness has led her into a PhD in equine biomechanics. PMID- 27256276 TI - The making of ESSKA: from an organization to an institution. PMID- 27256275 TI - Morphological features that can predict BRAFV600E -mutated carcinoma in paediatric thyroid cytology. AB - OBJECTIVE: BRAFV600E represents the most common diagnostic marker in papillary thyroid carcinoma (PTC). A few papers have demonstrated the correlation between BRAFV600E and specific morphological findings on PTCs in the adult population. This is the first reported series investigating cytological morphological parameters in paediatric thyroid carcinoma. METHODS: One hundred and nineteen paediatric samples (56 male and 63 female patients), diagnosed in the period between April 2013 and July 2015, were enrolled in the study. Fifteen patients with inadequate results were excluded. Cytological cases were processed with liquid-based cytology (LBC). BRAFV600E and immunocytochemistry for the VE1 antibody were performed on LBC. RESULTS: The diagnostic series included 10 mutated and 94 wild-type (WT) cases. Twenty two percent surgical samples showed 96% cytohistological concordance. The morphological analysis revealed plump cells (abundant eosinophilic cytoplasm and PTC nuclei) in all 10 mutated cases with only four cases showing a focal (less than 20% of the cells) plump component. None of the WT showed plump cells. A sickle nuclear shape was seen only in the mutated cases. VE1 yielded 100% positivity on mutated cases with three cytohistological discrepancies. CONCLUSIONS: The BRAFV600E mutation is also seen in paediatric cytology and the morphological features showed a high accuracy as both predictive mutational parameters and a helpful aid in management mainly of the aggressive BRAFV600E mutated carcinomas. PMID- 27256278 TI - Clinical failure after Dresden repair of mid-substance Achilles tendon rupture: human cadaveric testing. AB - PURPOSE: The purpose of this study was to describe the angle of clinical failure during cyclical mobilization exercises in the Achilles tendon of human cadaveric specimens that were repaired using the Dresden technique and FiberWire(r) No. 2. The secondary aim was to identify the secure limit of mobilization, the type of failure, and the type of apposition. METHODS: The lower limbs of eight males (mean age: 60.3 +/- 6.3 years) were repaired with the Dresden technique following complete, percutaneous mid-substance Achilles tendon rupture. A basal tension of 10 N at 30 degrees of plantarflexion was placed on each specimen. The angle of the ankle during clinical failure (tendon ends separation >5 mm) was then tested via cyclical exercises (i.e. 100 cycles between 30 degrees and 15 degrees of plantarflexion; 100 cycles between 15 degrees of plantarflexion and 0 degrees ; 100 cycles between 0 degrees and 15 degrees of dorsiflexion; and 100 cycles between 15 degrees of dorsiflexion and full dorsiflexion). Clinical failure was determined using the Laplacian edge detection filter, and the angle of clinical failure was obtained using a rotatory potentiometer aligned in relation to the intermalleolar axis of each foot specimen. The type of failure (knot, tendon, or suture) and apposition (termino-terminal or non-termino-terminal) were determined. Descriptive statistics were used to obtain the mean; standard deviation; 95 % confidence interval; 1st, 25th, 50th, 75th, and 100th percentiles; and the standard error of the mean for angle data. Proportions were used to describe the type of failure and apposition. RESULTS: The main results were a mean angle of clinical failure equal to 12.5 degrees of plantarflexion, a limit of mobilization equal to 14.0 degrees of plantarflexion, tendon failure type, and non-termino-terminal apposition in all specimens. CONCLUSIONS: While the mean angle of clinical failure in human cadaveric models was 12.5 degrees of plantarflexion, after 14.0 degrees of plantarflexion, the percutaneous Dresden technique was found insecure for cyclical mobilization exercises, with a 5 % range of error. These findings are clinically relevant as they provide mechanical limits for diminishing the risk of Achilles lengthening during immediate rehabilitation. PMID- 27256277 TI - In vivo posterior cruciate ligament elongation in running activity after anatomic and non-anatomic anterior cruciate ligament reconstruction. AB - PURPOSE: The goals of this study were to (1) investigate the in vivo elongation behaviour of the posterior cruciate ligament (PCL) during running in the uninjured knee and (2) evaluate changes in PCL elongation during running after anatomic or non-anatomic anterior cruciate ligament (ACL) reconstruction. METHODS: Seventeen unilateral ACL-injured subjects were recruited after undergoing anatomic (n = 9) or non-anatomic (n = 8) ACL reconstruction. Bilateral high-resolution CT scans were obtained to produce 3D models. Anterolateral (AL) and posteromedial (PM) bundles insertion sites of the PCL were identified on the 3D CT scan reconstructions. Dynamic knee function was assessed during running using a dynamic stereo X-ray (DSX) system. The lengths of the AL and PM bundles were estimated from late swing through mid-stance. The contralateral knees served as normal controls. RESULTS: Control knees demonstrated a slight decrease in AL bundle and a significant decrease in PM bundle length following foot strike. Length and elongation patterns of the both bundles of the PCL in the anatomic ACL reconstruction group were similar to the controls. However, the change in dynamic PCL length was significantly greater in the non-anatomic group than in the anatomic reconstruction group after foot strike (p < 0.05). CONCLUSION: The AL bundle length decreased slightly, and the PM bundle length significantly decreased after foot strike during running in uninjured knees. Anatomic ACL reconstruction maintained normal PCL elongation patterns more effectively than non-anatomic ACL reconstruction during high-demand, functional loading. These results support the use of anatomic ACL reconstruction to achieve normal knee function in high-demand activities. LEVEL OF EVIDENCE: Case-control study, Level III. PMID- 27256279 TI - Perceived barriers and enablers of physical activity in postpartum women: a qualitative approach. AB - BACKGROUND: Postpartum women's recovery from birth can be assisted through increased physical activity (PA). However, women face substantial barriers to participating in exercise and require support to enable them to benefit from increased PA. METHODS: This study sought to explore women's beliefs about and experiences of PA and exercise during the 6 weeks to 12 months postpartum period. A cohort of 14 postpartum women from a survey study of the barriers and enablers to exercise participation agreed to take part in interview sessions to provide an in-depth understanding of the women's perceptions of the postpartum period and their physical activity during this time. RESULTS: Findings are presented with reference to the social ecological framework and indicate postpartum women face substantial personal and environmental barriers to PA and exercise participation: fatigue, a lack of motivation and confidence, substantial time constraints, lack of access to affordable and appropriate activities and poor access to public transport. In contrast, enablers such as possessing greater social support, in particular partner support, improved PA and exercise participation. CONCLUSIONS: The findings encourage facilitation of exercise through mothers' groups, mothers' exercise clubs or postnatal classes suggesting behavioral and social change is needed. Interaction between individuals, community, organizations and policy makers is required. In addition, the provision of specifically tailored and appropriate exercise programs could potentially enable increased PA in postpartum women, thereby improving their health. PMID- 27256280 TI - Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II). AB - INTRODUCTION: Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. METHODS: Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. RESULTS: A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6+/-0.7 vs. 1.4+/-0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. CONCLUSION: The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. PMID- 27256281 TI - Substrate-tuning of correlated spin-orbit oxides revealed by optical conductivity calculations. AB - We have systematically investigated substrate-strain effects on the electronic structures of two representative Sr-iridates, a correlated-insulator Sr2IrO4 and a metal SrIrO3. Optical conductivities obtained by the ab initio electronic structure calculations reveal that the tensile strain shifts the optical peak positions to higher energy side with altered intensities, suggesting the enhancement of the electronic correlation and spin-orbit coupling (SOC) strength in Sr-iridates. The response of the electronic structure upon tensile strain is found to be highly correlated with the direction of magnetic moment, the octahedral connectivity, and the SOC strength, which cooperatively determine the robustness of Jeff = 1/2 ground states. Optical responses are analyzed also with microscopic model calculation and compared with corresponding experiments. In the case of SrIrO3, the evolution of the electronic structure near the Fermi level shows high tunability of hole bands, as suggested by previous experiments. PMID- 27256283 TI - Gillian Gandy. PMID- 27256282 TI - From starting mechanical ventilation to ventilator-associated pneumonia, choosing the right moment to start antibiotic treatment. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) can have a clear onset or may be a result of the gradual appearance of symptoms and signs of VAP (gradual VAP). The aim of this paper is to describe the VAP development process with the intention of discriminating between those pneumonias with a clear beginning and those that are diagnosed after a period of maturation. In addition, we evaluate the effect of the starting time of antibiotic treatment in both situations. METHODS: Consecutive ventilated patients fulfilling VAP criteria were included. The patients were monitored for clinical, microbiological, and inflammatory signs. Patients with VAP were classified into two groups: (1) nongradual VAP (patients in whom all VAP criteria were detected for the first time on the day of diagnosis) and (2) gradual VAP (progressive appearance of signs and symptoms throughout the pre-VAP period [<96 h to >24 h before VAP diagnosis]). RESULTS: A total of 71 patients with VAP were identified, of whom 43 (61 %) had gradual VAP, most of whom (n = 38, 88 %) had late-onset VAP. Antibiotic treatment was given to 34 (79 %) patients with gradual VAP in the pre-VAP period, and empirical antibiotic treatment was appropriate in 22 patients (51 %). The patients with an appropriate empirical treatment had a higher percentage of early clinical response to treatment (68 % [n = 15] vs. 28 % [n = 7]; p = 0.009). An attempt was made to find a diagnostic test capable of identifying the infectious process underway, but clinical scales and biomarkers of inflammation helped us to achieve acceptable results. CONCLUSIONS: Gradual emergence of VAP, mainly of late onset, is a common condition. Clinicians should be aware of this gradual onset of the infection to establish an early antibiotic treatment, even before the classic diagnostic criteria for VAP are applied. PMID- 27256284 TI - A Simple Spectrofluorimetric Method Based on Quenching of a Nickel(II) Phthalocyanine Complex to Determine Iron (III). AB - A new nickel(II)-phthalocyanine complex (NiPc) was synthesized and used as a fluorescent ligand in determination of iron in real samples. The NiPc compound, when excited at 350 nm, decreases of emission with increases of the iron(III) concentration at 425 nm were used analytical response in a modified standard addition method. The method was validated by analyzing two certified reference materials (CRM-SA-C Sandy Soil C and Mixed Polish Herbs (INCT-MPH-2). Food and drug samples were digested in a closed microwave system using nitric acid and hydrogen peroxide. Therefore, all iron in the samples converted to iron(III) ion. These solutions were used directly in determination of iron(III) ion. No cleanup or enrichment of the solutions was required. The calibration graph was linear until 14.00 MUg mL(-1). Detection limit and quantification limit were 1.29 MUg mL(-1) and 3.88 MUg mL(-1), respectively. The method provided accurate results for the majority of the food samples tested, including spanich, dill, mint, purslane, rocket, red lentils, dry beans and two iron medicinal tablets. Also, the high recovery (95.6 %) was obtained for a fortified stream water sample. The simple and cost-effective method is suitable for monitoring total iron concentration in foods and drug samples. PMID- 27256285 TI - Synthesis and Optoelectronic Properties of Thiophene Donor and Thiazole Acceptor Based Blue Fluorescent Conjugated Oligomers. AB - We report on the synthesis and characterization of low band gap, blue light emitting and thermal stable conjugated oligomer by Wittig condensation. Thiophene and thiazole type of donor-acceptor based series of conjugated oligomers, Oligo 4,5-bis-[2-[5-[2-thiophene-2-yl-vinyl]thiophene-2-yl]-vinyl]-thiazole (OBTV-TZ) and Oligo-2,4,5-Tris-[2-[5-[2-thiophene-2-yl-vinyl]thiophene-2-yl]-vinyl] thiazole (OTTV-TZ) were synthesized. These oligomers were confirmed by FT-IR and (1)H-NMR and LC/MS analysis. The effect of the number of thiophene rings on the optical, electrochemical, thermal and morphological properties of the oligomers were systematically investigated. Both oligomers were exhibited almost same absorption wavelength in methanol solution (lambdamax = 365 nm and 369 nm) which indicates both oligomers illustrate similar intra molecular charge transfer (ICT). In solid state, the oligomers were exhibited broadening peaks with higher onset absorptions (lambdamax = 600 nm and 580 nm). The photoluminescence absorption spectrum of the oligomers was observed at 433 nm and 434 nm respectively in methanol solution with blue emission. The electrochemical band gap ([Formula: see text]) of the OBTV-TZ was 1.55 eV (low band gap) and OTTV-TZ was exhibited greater highest occupied molecular orbital (HOMO) value (E HOMO = 6.6 eV). Moreover morphological parameters of both oligomer film of 2D and 3D diagrams were observed by using AFM studies. PMID- 27256287 TI - Lessons on resilience: Learning to manage complexity. PMID- 27256286 TI - A Small Molecule Activator of p300/CBP Histone Acetyltransferase Promotes Survival and Neurite Growth in a Cellular Model of Parkinson's Disease. AB - Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by motor and non-motor symptoms, resulting from the degeneration of nigrostriatal dopaminergic neurons and peripheral autonomic neurons. Given the limited success of neurotrophic factors in clinical trials, there is a need to identify new small molecule drugs and drug targets to develop novel therapeutic strategies to protect all neurons that degenerate in PD. Epigenetic dysregulation has been implicated in neurodegenerative disorders, while targeting histone acetylation is a promising therapeutic avenue for PD. We and others have demonstrated that histone deacetylase inhibitors have neurotrophic effects in experimental models of PD. Activators of histone acetyltransferases (HAT) provide an alternative approach for the selective activation of gene expression, however little is known about the potential of HAT activators as drug therapies for PD. To explore this potential, the present study investigated the neurotrophic effects of CTPB (N-(4 chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide), which is a potent small molecule activator of the histone acetyltransferase p300/CBP, in the SH-SY5Y neuronal cell line. We report that CTPB promoted the survival and neurite growth of the SH-SY5Y cells, and also protected these cells from cell death induced by the neurotoxin 6-hydroxydopamine. This study is the first to investigate the phenotypic effects of the HAT activator CTPB, and to demonstrate that p300/CBP HAT activation has neurotrophic effects in a cellular model of PD. PMID- 27256288 TI - Comparison between pressure-recording analytical method (PRAM) and femoral arterial thermodilution method (FATD) cardiac output monitoring in an infant animal model of cardiac arrest. AB - BACKGROUND: The pressure-recording analytical method is a new semi-invasive method for cardiac output measurement (PRAM). There are no studies comparing this technique with femoral artery thermodilution (FATD) in an infant animal model. METHODS: A prospective study was performed using 25 immature Maryland pigs weighing 9.5 kg. Fifty-eight simultaneous measurements of cardiac index (CI) were made by FATD and PRAM at baseline and after return of spontaneous circulation. Differences, correlation, and concordance between both methods were analyzed. The ability of PRAM to track changes in CI was explored with a polar plot. RESULTS: Mean CI measurements were 4.5 L/min/m(2) (95 % CI, 4.2-4.8 L/min/m(2); coefficient of variation, 27 %) by FATD and 4.0 L/min/m(2) (95 % CI, 3.6-4.3 L/min/m(2); coefficient for variation, 37 %) by PRAM (difference, 0.5 L/min/m(2); 95 % CI for the difference, 0.1-1.0 L/min/m(2); p = 0.003; n = 58). No correlation between both methods was observed (r = 0.170, p = 0.20). Limits of agreement were -2.9 to 4.0 L/min/m(2) (-69.9 to 84.9 %). Percentage error was 80.6 %. Only 26.1 % of data points lied within an absolute deviation of +/-30 degrees from the polar axis. CONCLUSIONS: No correlation nor concordance between both methods was observed. Limits of agreement and percentage of error were high and clinically not acceptable. No concurrence between both methods in CI changes was observed. PRAM is not a useful method for measurement of the CI in this pediatric model of cardiac arrest. PMID- 27256289 TI - Understanding the futility of countries' obligations for health rights: realising justice for the global poor. AB - BACKGROUND: Although health is a right of all individuals without any distinction, the realisation of this right has remained very difficult for the marginalised populations of poor countries. Inequitable distribution of health opportunities globally is a major factor in explaining why this is the case. Whereas the Protection, Promotion and Fulfilment of the health rights of poor country citizens are a joint responsibility of both domestic and external governments, most governments flout their obligations. So far disproportionate effort has been dedicated to reaffirming and interpreting these obligations as opposed to investigating the fundamental question regarding why these obligations have nevertheless remained largely unfulfilled. Further the normative question regarding what ought to be done about the shortcomings of current obligations has been largely ignored. METHODS: We conduct a critical content analysis of existing literature on efforts towards the realisation of the health rights of marginalised populations in our attempt to ascertain their capacity to guarantee basic health opportunities to marginalised populations. In our analysis we treat issues of 'health rights' and 'justice in global health' as having unity of purpose - guaranteeing basic health opportunities to the marginalised populations. RESULTS: We identify two sets of reasons for the failure of present obligations for global distributive justice in general: a set of 'superficial reasons' and a set of 'fundamental reasons' which account for the superficial reasons. DISCUSSION: In order to overcome these reasons we propose a strategy which consists in specifying a number of minimum and less-demanding obligations for both external and domestic governments to guarantee to all individuals a certain threshold of health goods and services. We argue that these minimum obligations can be freely accepted and fully complied with or enforced with "a thin system of enforcement" without significant threat to national sovereignty and autonomy. CONCLUSION: The futility of countries' obligations for the health rights of the global poor as is the case with global distributive injustice is because of lack of political will to specify and enforce such obligations. Minimum obligations should be specified and enforced with a "thin system" which is consistent with principles of national sovereignty and autonomy. PMID- 27256290 TI - Internalised stigma in people with rheumatoid arthritis: a cross sectional study to establish the psychometric properties of the ISMI-RA. AB - BACKGROUND: Internalised stigma is theorized to be the internalisation and legitimisation of stereotypes of the diagnosis held in society and has not been quantified within patients with Rheumatoid Arthritis. This study aimed to: validate a modified version of a measure of internalised stigma, (the Internalised Stigma of Mental Illness scale, ISMI) for use in a group of patients diagnosed with rheumatoid arthritis; establish the consistency of the construct being measured, and to explore the levels of internalised stigma within this group. METHODS: A cross-sectional survey was conducted in London, UK with participants receiving out-patient treatment for Rheumatoid Arthritis. Participants completed the ISMI-Rheumatoid Arthritis (ISMI-RA) and a measure of self-esteem. RESULTS: One hundred respondents were interviewed by phone. The ISMI RA was found to be reliable using a measure of internal consistency (alpha = 0.85) showed concurrent validity with the Index of Self Esteem (r = 0.58, p < 0.01) and discriminant validity with no association with gender (t = 1.43, p = 0.61). A quarter of respondents reported internalised stigma to a 'severe' level. Acceptability and feasibility were established. A confirmatory factor analysis provided some support for the model of internalised stigma. CONCLUSIONS: The application of the ISMI-RA among the Rheumatoid Arthritis population looks promising. Internalised stigma was found to be present within this group. More research is needed to generalize these results and to explore the effects of internalised stigma on treatment adherence and quality of life. PMID- 27256291 TI - Cross-cultural adaptation and validation of the Social Comfort Questionnaire for Brazilian adult survivors of burns. AB - PURPOSE: Burn patients may encounter social barriers and stigmatization. The objectives of this study were to adapt the Social Comfort Questionnaire (SCQ) into Brazilian Portuguese and to assess the psychometric properties of the adapted version. METHODS: Cross-cultural adaptation of the 8 items of the SCQ followed international guidelines. We interviewed 240 burn patients and verified the SCQ internal consistency, test-retest reliability and construct validity, correlating the scores with depression [Beck Depression Inventory (BDI)], affect/body image and interpersonal relationships [Burns Specific Health Scale Revised (BSHS-R)] and self-esteem [Rosenberg's Self-Esteem Scale (RSES)]. We also performed a confirmatory factor analysis (CFA). RESULTS: The cross-cultural adaptation resulted in minor semantic modifications to the original SCQ version. After CFA, a reduced 6-item version showed satisfactory fit to the one-factor model (RMSEA = 0.05, CFI = 0.99, TLI = 0.99). Cronbach alpha's was 0.80, and test retest intraclass correlation coefficient was 0.86. The final version presented a strong negative correlation with depression (BDI), and strong positive correlations with affect/body image (BSHS-R), interpersonal relationships (BSHS R) and self-esteem (RSES) (all p < 0.001). CONCLUSION: The results showed that the SCQ Brazilian Portuguese adapted version complies with the validity and reliability criteria required for an instrument assessing social comfort in Brazilian burn patients. The Brazilian version yields a single score that is easy to interpret and well understood by patients. PMID- 27256292 TI - Microglial immunophenotype in dementia with Alzheimer's pathology. AB - BACKGROUND: Genetic risk factors for Alzheimer's disease imply that inflammation plays a causal role in development of the disease. Experimental studies suggest that microglia, as the brain macrophages, have diverse functions, with their main role in health being to survey the brain parenchyma through highly motile processes. METHODS: Using the Medical Research Council Cognitive Function and Ageing Studies resources, we have immunophenotyped microglia to investigate their role in dementia with Alzheimer's pathology. Cerebral cortex obtained at post mortem from 299 participants was analysed by immunohistochemistry for cluster of differentiation (CD)68 (phagocytosis), human leukocyte antigen (HLA)-DR (antigen presenting function), ionized calcium-binding adaptor molecule (Iba1) (microglial motility), macrophage scavenger receptor (MSR)-A (plaque-related phagocytosis) and CD64 (immunoglobulin Fcgamma receptor I). RESULTS: The presence of dementia was associated positively with CD68 (P < 0.001), MSR-A (P = 0.010) and CD64 (P = 0.007) and negatively with Iba1 (P < 0.001). Among participants without dementia, the cognitive function according to the Mini-Mental State Examination was associated positively with Iba1 (P < 0.001) and negatively with CD68 (P = 0.033), and in participants with dementia and Alzheimer's pathology, positively with all microglial markers except Iba1. Overall, in participants without dementia, the relationship with Alzheimer's pathology was negative or not significant, and positive in participants with dementia and Alzheimer's pathology. Apolipoprotein E (APOE) epsilon2 allele was associated with expression of Iba1 (P = 0.001) and MSR-A (P < 0.001) and APOE epsilon4 with CD68, HLA-DR and CD64 (P < 0.001). CONCLUSIONS: Our findings raise the possibility that in dementia with Alzheimer's pathology, microglia lose motility (Iba-1) necessary to support neurons. Conversely, other microglial proteins (CD68, MSR-A), the role of which is clearance of damaged cellular material, are positively associated with Alzheimer's pathology and impaired cognitive function. In addition, our data imply that microglia may respond differently to Abeta and tau in participants with and without dementia so that the microglial activity could potentially influence the likelihood of developing dementia, as supported by genetic studies, highlighting the complexity and diversity of microglial responses. PMID- 27256293 TI - Mass or total surface area with aerosol size distribution as exposure metrics for inflammatory, cytotoxic and oxidative lung responses in rats exposed to titanium dioxide nanoparticles. AB - There is currently no consensus on the best exposure metric(s) for expressing nanoparticle (NP) dose. Although surface area has been extensively studied for inflammatory responses, it has not been as thoroughly validated for cytotoxicity or oxidative stress effects. Since inhaled NPs deposit and interact with lung cells based on agglomerate size, we hypothesize that mass concentration combined with aerosol size distribution is suitable for NP risk assessment. The objective of this study was to evaluate different exposure metrics for inhaled 5 nm titanium dioxide aerosols composed of small (SA < 100 nm) or large (LA > 100 nm) agglomerates at 2, 7, and 20 mg/m3 on rat lung inflammatory, cytotoxicity, and oxidative stress responses. We found a significant positive correlation ( r = 0.98, p < 0.01) with the inflammatory reaction, measured by the number of neutrophils and the mass concentration when considering all six (SA + LA) aerosols. This correlation was similar ( r = 0.87) for total surface area. Regarding cytotoxicity and oxidative stress responses, measured by lactate dehydrogenase and 8-isoprostane, respectively, and mass or total surface area as an exposure metric, we observed significant positive correlations only with SA aerosols for both the mass concentration and size distribution ( r > 0.91, p < 0.01), as well as for the total surface area ( r > 0.97, p < 0.01). These data show that mass or total surface area concentrations alone are insufficient to adequately predict oxidant and cytotoxic pulmonary effects. Overall, our study indicates that considering NP size distribution along with mass or total surface area concentrations contributes to a more mechanistic discrimination of pulmonary responses to NP exposure. PMID- 27256294 TI - Conservative treatment and follow-up of vaginal Gartner's duct cysts: a case series. AB - BACKGROUND: In women, during embryologic development, the paired Mullerian (paramesonephric) ducts fuse distally and develop into the uterus, cervix, and upper vagina. If the Wolffian ducts persist in vestigial form, they can lead to Gartner's cysts, mainly located in the right wall of the vagina. This is one of the few studies of Gartner's cysts with a series of consecutive cases over a long period of time who were exclusively subject to clinical observation. Although Gartner's cysts are found in approximately 0.1 to 0.2% of women, controversy exists regarding the course of action to be taken. CASE PRESENTATION: We describe the cases of four women who were 38-years old, 53-years old, 37-years old, and 49 years old at their first appointment and who were of mixed ethnicity, mixed ethnicity, black, and mixed ethnicity respectively. The follow-up of these patients ranged from 2 to 17 years. In these four cases the location of the cysts was the right wall of the vagina. Transvaginal ultrasound was the test of choice for diagnostic confirmation. In the cases presented in this study, the women were asymptomatic and chose to be observed clinically. CONCLUSIONS: This is the first study reporting long-term clinical observation of these lesions. This study shows that conservative treatment can be a safe option for asymptomatic patients with vaginal Gartner's duct cysts. PMID- 27256295 TI - Association Between Relative Anemia and Early Functional Recovery After Severe Traumatic Brain Injury (TBI). AB - BACKGROUND: Severe traumatic brain injury is associated with a multi-systemic response and changes in metabolic demand. Patients requiring intracranial pressure monitoring or cerebrospinal fluid diversion, often signifies a greater severity of injury. For this group, the association between RBC transfusion, transfusion thresholds, and clinical recovery is unknown. In this study, we studied the association between transfusion and clinical recovery for severe traumatic brain injury patients requiring external ventricular drain or intracranial pressure monitor placement. METHODS: Eighty-nine patients with a primary diagnosis of traumatic brain injury requiring implantation of either an intracranial pressure monitor or external ventricular drainage device were identified. All patients were managed in a Level 1 Trauma facility by board certified neuro-intensive care practitioners for the course of their intensive care unit duration. The correlation between transfusion and clinical recovery, defined by change in Glasgow Coma Scale was assessed. RESULTS: Thirty-four patients required surgical decompression, and 56.18 % of the cumulative cohort were transfused during admission. Overall, transfusion was not associated with significant clinical recovery (change in GCS > 3) for Hgb threshold of 7 mg/dL (<3, 29.03 vs. >=3, 37.93 %; p = 0.49), nor for higher stratifications (8 mg/dL, p = 0.63; 9 mg/dL, p = 0.79, 10 mg/dL, p = 1). For patients who required transfusions at thresholds >=8 mg/dL, there was a positive association with decreased length of hospitalization, [p = 0.01; <8 mg/dL: 22 (12-33), >=8 mg/dL: 14 (7.75-20)] [median (IQR)]. Similarly, length of ICU stay was shorter for patients transfused at thresholds >=9 mg/dL, (p = 0.02). CONCLUSIONS: From our studies, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a decrease in length of hospitalization for patients with transfusion thresholds of Hgb >= 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population. In patients admitted for primary severe traumatic brain injury, we demonstrate no significant clinical benefit associated with stratified transfusion goals; however, there was a noticeable decrease in length of hospitalization for patients with transfusion thresholds of Hgb >= 8 mg/dL. Larger, randomized controlled trials may be required to more accurately assess outcomes in this patient population. PMID- 27256297 TI - Cocoa polyphenols and fiber modify colonic gene expression in rats. AB - PURPOSE: Cocoa intake has been associated with health benefits, improving cardiovascular function and metabolism, as well as modulating intestinal immune function. The aim of this study was to take an in-depth look into the mechanisms affected by the cocoa intake by evaluating the colonic gene expression after nutritional intervention, and to ascertain the role of the fiber of cocoa in these effects. METHODS: To achieve this, Wistar rats were fed for 3 weeks with either a reference diet, a diet containing 10 % cocoa (C10), a diet based on cocoa fiber (CF) or a diet containing inulin (I). At the end of the study, colon was excised to obtain the RNA to evaluate the differential gene expression by microarray. Results were validated by RT-PCR. RESULTS: The C10 group was the group with most changes in colonic gene expression, most of them down-regulated but a few in common with the CF diet. The C10 diet significantly up-regulated the expression of Scgb1a1 and Scnn1 g and down-regulated Tac4, Mcpt2, Fcer1a and Fabp1 by twofold, most of them related to lipid metabolism and immune function. The CF and I diets down-regulated the expression of Serpina10 and Apoa4 by twofold. Similar patterns of expression were found by PCR. CONCLUSION: Most of the effects attributed to cocoa consumption on genes related to the immune system (B cell and mast cell functionality) and lipid metabolism in the colon tissue were due not only to its fiber content, but also to the possible contribution of polyphenols and other compounds. PMID- 27256298 TI - Relationship of equol production between children aged 5-7 years and their mothers. AB - PURPOSE: The factors responsible for the production of isoflavone metabolites have not yet been identified. We aimed to examine the relationships of equol production between mother and child in a birth cohort in Japan. METHODS: Subjects were a part of the participants in a longitudinal study on pregnant women and their offspring. When children were 5-7 years old, mothers and children were asked to reply to a questionnaire on lifestyles and a 3-day child's dietary record. Mothers and children were given a bar-shaped soy snack (Soyjoy(r)) daily on two consecutive days (soy challenge). The snack contained 14 mg of overall soy isoflavones as the sum of aglycones and the glucosides for mothers and 7.5 mg for children. On the morning of day 0 and 3, they were asked to mail their first-void urines. Urinary isoflavone metabolites of 159 mother-child pairs were measured by a high-performance liquid chromatography method. RESULTS: Equol producers were 35.5 % among mothers and 13.8 % among children. Equol producer status of a child was neither associated with dietary intake nor with urinary levels of daidzein and genistein. After multiple adjustments for potential confounders, the estimated relative risk of equol producer was 2.75 (95 % confidence interval 1.00, 7.52) among children whose mother was an equol producer, compared with children whose mother was a non-producer. CONCLUSION: Child's equol production was associated with the mother's equol producer status. The effects of maternal factors on child's equol production should be studied further. PMID- 27256299 TI - The 360 photography: a new anatomical insight of the sphenoid bone. Interest for anatomy teaching and skull base surgery. AB - Skull base architecture is tough to understand because of its 3D complex shape and its numerous foramen, reliefs or joints. It is especially true for the sphenoid bone whom central location hinged with most of skull base components is unique. Recently, technological progress has led to develop new pedagogical tools. This way, we bought a new real-time three-dimensional insight of the sphenoid bone that could be useful for the teacher, the student and the surgeon. High-definition photography was taken all around an isolated dry skull base bone prepared with Beauchene's technique. Pictures were then computed to provide an overview with rotation and magnification on demand. From anterior, posterior, lateral or oblique views and from in out looks, anatomical landmarks and subtleties were described step by step. Thus, the sella turcica, the optic canal, the superior orbital fissure, the sphenoid sinus, the vidian canal, pterygoid plates and all foramen were clearly placed relative to the others at each face of the sphenoid bone. In addition to be the first report of the 360 Photography tool, perspectives are promising as the development of a real-time interactive tridimensional space featuring the sphenoid bone. It allows to turn around the sphenoid bone and to better understand its own special shape, numerous foramen, neurovascular contents and anatomical relationships. This new technological tool may further apply for surgical planning and mostly for strengthening a basic anatomical knowledge firstly introduced. PMID- 27256300 TI - Prevalence of Celiac Disease in Patients with Autoimmune Thyroid Disease: A Meta Analysis. AB - BACKGROUND: Several screening studies have indicated an increased prevalence of celiac disease (CD) among individuals with autoimmune thyroid disease (ATD), but estimates have varied substantially. OBJECTIVE: The aim of this study was to examine the prevalence of CD in patients with ATD. METHOD: A systematic review was conducted of articles published in PubMed Medline or EMBASE until September 2015. Non-English papers with English-language abstracts were also included, as were research abstracts without full text available when relevant data were included in the abstract. Search terms included "celiac disease" combined with "hypothyroidism" or "hyperthyroidism" or "thyroid disease." Fixed-effects inverse variance-weighted models were used. Meta-regression was used to examine heterogeneity in subgroups. RESULTS: A pooled analysis, based on 6024 ATD patients, found a prevalence of biopsy-confirmed CD of 1.6% [confidence interval (CI) 1.3-1.9%]. Heterogeneity was large (I(2) = 70.7%). The prevalence was higher in children with ATD (6.2% [CI 4.0-8.4%]) than it was in adults (2.7%) or in studies examining both adults and children (1.0%). CD was also more prevalent in hyperthyroidism (2.6% [CI 0.7-4.4%]) than it was in hypothyroidism (1.4% [CI 1.0 1.9%]). CONCLUSIONS: About 1/62 patients with ATD have biopsy-verified CD. It is argued that patients with ATD should be screened for CD, given this increased prevalence. PMID- 27256301 TI - Lysosome-mitochondria-mediated apoptosis specifically evoked in cancer cells induced by gold nanorods. AB - AIM: The main aim of this article is to explain the apoptosis mechanisms of cancer cells specifically triggered by gold nanorods (GNRs). MATERIALS & METHODS: GNRs were synthesized and optimized, the lysosome damage, cathepsin D, mitochondrial membrane potential, caspase-9, cleaved caspase-9, caspase-3 and intracellular GNRs location related to apoptosis was systematically evaluated. RESULTS: GNRs specifically induce cancer cell apoptosis while posing a negligible impact on normal cells. After incubation with GNRs, the lysosomal permeability in cancer cells as indicated by cathepsin D was markedly higher than that in normal cells and resulted in an obvious decrease in mitochondrial membrane potential. Western blot analysis further confirmed that apoptosis occurred through caspase-9 and caspase-3 activation following mitochondrial damage. Transmission electron microscope images showed that GNRs did not appear in most of the damaged mitochondria but mainly accumulated in lysosomes. CONCLUSION: These findings indicated that GNR-induced apoptosis specifically in cancer cells by affecting lysosomes and mitochondria. PMID- 27256302 TI - Glaucoma treatment adherence at a United Kingdom general practice. AB - PurposeTo estimate patient adherence with glaucoma therapy and identify factors associated with adherence using computerised patient prescribing records.MethodsIdentification of patients diagnosed with glaucoma, ocular hypertension or suspect glaucoma and/or prescribed topical glaucoma medications registered at a United Kingdom general practice with 13 422 patients. Adherence was defined as the average difference in the actual number of prescriptions collected annually compared to twelve prescriptions required annually (one bottle per month) over the duration of treatment.ResultsOverall, 278 patients were identified of which 139 (50%) were male. The average age was 72 years (range: 22 100). A total of 206 patients (74%) were prescribed glaucoma treatment. Adherence varied significantly between age groups with younger patients demonstrating poorest adherence (P=0.0347). There was no statistical difference when comparing medication class, diagnosis, co-morbidities, or the number of drops being taken.ConclusionsGlaucoma treatment adherence improves with increasing age. Older patients require more prescriptions and may be experiencing drop wastage. Younger patients should be targeted with educational interventions to improve their understanding of glaucoma, and older patients for drop technique review. General practices are well placed to provide such interventions. PMID- 27256296 TI - Catecholamines and cognition after traumatic brain injury. AB - Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person's catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain 'networks' that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID- 27256303 TI - Associations of retinal artery occlusion and retinal vein occlusion to mortality, stroke, and myocardial infarction: a systematic review. AB - Retinal vascular events are perceived to be related to various cardiovascular complications. We conducted a systematic review to assess the relationship between retinal artery/vein occlusions (RAO/RVO) and the incidence of mortality, stroke, and myocardial infarction (MI). A comprehensive electronic literature search selected 93 relevant studies between 1992-2015: 16 articles qualified for inclusion (7 for mortality rate and MI, 11 for stroke). No published articles examined associations of RAO to mortality or MI, but only to stroke. Because of the heterogeneity of studies, no meta-analysis was performed. The association with mortality risk was highest at ~34.7% in RVO subgroup; whereas for MI, the risk was comparatively lower at 3.9-5.7% for RVO. There was no significant difference in stroke rate when comparing central and branch RVO subgroups (6.5%), but was significantly higher at 19.6-25% in RAO. There is a positive association of retinal vascular events to mortality, stroke, and MI. RAO is associated with a higher risk of stroke. Given that RAO and RVO patients would generally present to ophthalmologists, their high cardiovascular risk should include a referral for cardiovascular assessment as part of their management protocol. PMID- 27256304 TI - Uveitic macular edema. AB - Macular edema (ME) may complicate anterior, intermediate, and posterior uveitis, which may be because of various infectious, neoplastic or autoimmune etiologies. BRB breakdown is involved in the pathogenesis of Uveitic ME (UME). Optical coherence tomography has become a standard tool to confirm the diagnosis of macular thickening, due to its non-invasive, reproducible, and sensitive features. Retinal fluorescein and indocyanine green angiography is helpful to study the macula and screen for associated vasculitis, detect ischemic areas and preretinal, prepapillary or choroidal neovascular complications, and it may provide information about the etiology and be needed to assess the therapeutic response. UME due to an infection or neoplastic infiltration may require a specific treatment. If it remains persistent or occurs in other etiologies, immunomodulatory treatments may be needed. Intravitreal, subconjunctival, or subtenon corticosteroids are widely used. Their local use is contraindicated in glaucoma patients and limited by their short-lasting action. In case of bilateral sight-threatening chronic posterior uveitis, systemic treatments are usually needed, and corticosteroids are used as the standard first-line therapy. In order to reduce the daily steroid dose, immunosuppressive or immunomodulatory agents may be added, some of them being now available intravitreally. Ongoing prospective studies are assessing biotherapies and immunomodulators to determine their safety and efficacy in this indication. PMID- 27256305 TI - Trabeculectomy with ologen in secondary glaucomas following failed trabeculectomy with MMC: comparative study. AB - PurposeWe aimed to assess the IOP-lowering effect of trabeculectomy with ologen in refractory secondary glaucoma following failed trabeculectomy with mitomycin C (MMC), and to compare its surgical outcome between open angle (SOAG) and angle closure (SACG) cases.MethodsThis is a prospective interventional comparative study conducted on 40 eyes (40 patients) with medically uncontrolled secondary glaucoma. Patients were divided into group A: 18 eyes (18 patients) with SOAG, and group B: 22 eyes (22 patients) with SACG. All patients underwent trabeculectomy with insertion of ologen implant. Intraocular pressure (IOP) measurement, SITA standard perimetry (Central 24-2), spectral domain optical coherence tomography (OCT) for retinal nerve fiber layer (RNFL) thickness, and anterior segment OCT for bleb morphology, were all done pre- and postoperatively. Primary outcome measures were comparing preoperative to postoperative measurements and also comparing these measurements between SOAG and SACG. All patients were examined up to 1 year.ResultsWhen preoperative IOP was compared with postoperative IOP, in each group, there was a statistically significant difference (P<0.001). IOP percentage difference was statistically insignificantly different between both groups except at 1 month. According to Moorfields bleb grading system; postoperative bleb was better than the bleb of the previously failed trabeculectomy (P<0.001), and there was a significant difference between group A and B regarding bleb area. Total success rate was 100%; in group A, complete success was 100%, while in group B it was 72.7% (P=0.016).ConclusionOur results suggest that Ologen may be a useful alternative to MMC in repeat trabeculectomy. PMID- 27256306 TI - Chandelier retroillumination-assisted cataract surgery during vitrectomy. AB - PurposeTo present an alternative cataract surgical technique in patients with cataract and intravitreal hemorrhage.MethodsTwelve cases with poor fundus reflex caused by severe vitreus hemorrhage were included in the study. All patients underwent combined phaco surgery and 23-gauge vitrectomy. Chandelier retroillumination was inserted into the infusion trochar during the cataract operations and was used with low power (50-75%) in necessary steps.ResultsWe did not experience phaco complications or complications due to technique during surgery. Retroillumination assistance was especially useful during final stages of cataract surgery, particularly irrigation-aspiration of cortical material.ConclusionRetroillumination in absence of red fundus reflex may be helpful and can be practiced more often in cataract surgery combined with vitrectomy. PMID- 27256307 TI - Arrhythmia and Electrophysiological Effects of Chemotherapy: A Review. AB - IMPORTANCE: Cardiotoxicity is an important limiting factor in the use of antineoplastic agents. The risk of arrhythmia and the electrophysiological effects of these agents are poorly characterized though increasing evidence suggests a high prevalence of complications. OBSERVATIONS: Patients with substantial cardiovascular risk factors are often excluded from clinical trials, while the aging population of patients actually receiving therapies may have an underlying arrhythmogenic substrate due to comorbidities. Risk stratification of patients before the selection of a therapeutic regimen is essential. Given the regular use of combination therapies, the potential for arrhythmia of each agent must be fully understood. Despite limited data and understanding in clinical practice, decisions on whether to initiate specific therapies in high-risk patients and how to manage the associated complications are made regularly. CONCLUSIONS AND RELEVANCE: This review describes the observed arrhythmias and proposed mechanisms for several major classes of antineoplastic agents. It also provides recommendations for risk stratification, monitoring, prophylaxis, and therapy, emphasizing the need for a collaborative relationship between oncologists and cardiologists and areas for future research. PMID- 27256308 TI - Modulation of critical brain dynamics using closed-loop neurofeedback stimulation. AB - OBJECTIVE: EEG long-range temporal correlations (LRTCs) are a significant for both human cognition and brain disorders, but beyond suppression by sensory disruption, there are little means for influencing them non-invasively. We hypothesized that LRTCs could be controlled by engaging intrinsic neuroregulation through closed-loop neurofeedback stimulation. METHODS: We used a closed-loop stimulation paradigm where supra-threshold alpha-waves trigger visual flash stimuli while the subject performs the standard eyes-closed resting-state task. As a "sham" control condition, we applied similar stimulus sequences without the neurofeedback. RESULTS: Over three sessions, a significant difference in the LRTCs of alpha-band oscillations (U=89, p<0.028, Wilcoxon rank sum test) and their scalp topography (T=-2.92, p<0.010, T-test) emerged between the neurofeedback and sham conditions so that the LRTCs were stronger during neurofeedback than sham. No changes (F=0.16, p>0.69, ANOVA test) in the scalp topography of alpha-band power were observed in either condition. CONCLUSIONS: This study provides proof-of-concept for that EEG LRTCs, and hence critical brain dynamics, can be modulated with closed-loop stimulation in an automatic, involuntary fashion. We suggest that this modulation is mediated by an excitation inhibition balance change achieved by the closed-loop neuroregulation. SIGNIFICANCE: Automatic LRTC modulation opens novel avenues for both examining the functional roles of brain criticality in healthy subjects and for developing novel therapeutic approaches for brain disorders associated with abnormal LRTCs. PMID- 27256310 TI - Chemical characterization of high-molar-mass fractions in a Norway spruce knotwood ethanol extract. AB - The low-molar-mass (LMM) fraction, only, i.e., the GC-eluting compounds, which are mainly lignans, has been characterized in Norway spruce knotwood hydrophilic extracts previously. Of this fraction, many lignans and sesquilignans and all GC peaks supposedly representing dilignans remain unidentified. In this work, dilignans and the GC non-eluting compounds (the high-molar mass fractions, HMM) were characterized in a 7-hydroxymatairesinol-reduced knotwood ethanol extract of Norway spruce by using several fractionation and analytical techniques. A methyl tert-butyl ether (MTBE) insoluble fraction of the extract contained mainly HMM material, of which the main part was shown to consist of lignan oligomers. The oligolignans (with a molar mass up to approximately 3700 Da) seemed to be linked by 55' bonds, some of them containing one or two guaiacylglycerol ether units linked to the lignan by betaO4 or beta5 bonds. Several oligolignans were identified or tentatively identified. The MTBE soluble fraction, which accounted for the major part (81%) of the extract, contained mainly LMM material (lignans, sesqui- and dilignans). The part of the HMM material in the MTBE soluble fraction that was easily isolable (2%) seemed to contain polymers of fatty acids and alcohols, resin acids, and sterols. PMID- 27256309 TI - DNA Methylation Signature Reveals Cell Ontogeny of Renal Cell Carcinomas. AB - PURPOSE: DNA methylation is a heritable covalent modification that is developmentally regulated and is critical in tissue-type definition. Although genotype-phenotype correlations have been described for different subtypes of renal cell carcinoma (RCC), it is unknown if DNA methylation profiles correlate with morphological or ontology based phenotypes. Here, we test the hypothesis that DNA methylation signatures can discriminate between putative precursor cells in the nephron. EXPERIMENTAL DESIGNS: We performed deep profiling of DNA methylation and transcriptome in diverse histopathological RCC subtypes and validated DNA methylation in an independent dataset as well as in The Cancer Genome Atlas Clear Cell and Chromophobe Renal Cell Carcinoma Datasets. RESULTS: Our data provide the first mapping of methylome epi-signature and indicate that RCC subtypes can be grouped into two major epi-clusters: C1, which encompasses clear-cell RCC, papillary RCC, mucinous and spindle cell carcinomas and translocation RCC; C2, which comprises oncocytoma and chromophobe RCC. Interestingly, C1 epi-cluster displayed 3-fold more hypermethylation as compared with C2 epi-cluster. Of note, differentially methylated regions between C1 and C2 epi-clusters occur in gene bodies and intergenic regions, instead of gene promoters. Transcriptome analysis of C1 epi-cluster suggests a functional convergence on Polycomb targets, whereas C2 epi-cluster displays DNA methylation defects. Furthermore, we find that our epigenetic ontogeny signature is associated with worse outcomes of patients with clear-cell RCC. CONCLUSIONS: Our data define the epi-clusters that can discriminate between distinct RCC subtypes and for the first time define the epigenetic basis for proximal versus distal tubule derived kidney tumors. Clin Cancer Res; 22(24); 6236-46. (c)2016 AACR. PMID- 27256311 TI - Benchmarking the next generation of homology inference tools. AB - MOTIVATION: Over the last decades, vast numbers of sequences were deposited in public databases. Bioinformatics tools allow homology and consequently functional inference for these sequences. New profile-based homology search tools have been introduced, allowing reliable detection of remote homologs, but have not been systematically benchmarked. To provide such a comparison, which can guide bioinformatics workflows, we extend and apply our previously developed benchmark approach to evaluate the 'next generation' of profile-based approaches, including CS-BLAST, HHSEARCH and PHMMER, in comparison with the non-profile based search tools NCBI-BLAST, USEARCH, UBLAST and FASTA. METHOD: We generated challenging benchmark datasets based on protein domain architectures within either the PFAM + Clan, SCOP/Superfamily or CATH/Gene3D domain definition schemes. From each dataset, homologous and non-homologous protein pairs were aligned using each tool, and standard performance metrics calculated. We further measured congruence of domain architecture assignments in the three domain databases. RESULTS: CSBLAST and PHMMER had overall highest accuracy. FASTA, UBLAST and USEARCH showed large trade-offs of accuracy for speed optimization. CONCLUSION: Profile methods are superior at inferring remote homologs but the difference in accuracy between methods is relatively small. PHMMER and CSBLAST stand out with the highest accuracy, yet still at a reasonable computational cost. Additionally, we show that less than 0.1% of Swiss-Prot protein pairs considered homologous by one database are considered non-homologous by another, implying that these classifications represent equivalent underlying biological phenomena, differing mostly in coverage and granularity. AVAILABILITY AND IMPLEMENTATION: Benchmark datasets and all scripts are placed at (http://sonnhammer.org/download/Homology_benchmark). CONTACT: forslund@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27256312 TI - COCACOLA: binning metagenomic contigs using sequence COmposition, read CoverAge, CO-alignment and paired-end read LinkAge. AB - Motivation: The advent of next-generation sequencing technologies enables researchers to sequence complex microbial communities directly from the environment. Because assembly typically produces only genome fragments, also known as contigs, instead of an entire genome, it is crucial to group them into operational taxonomic units (OTUs) for further taxonomic profiling and down streaming functional analysis. OTU clustering is also referred to as binning. We present COCACOLA, a general framework automatically bin contigs into OTUs based on sequence composition and coverage across multiple samples. Results: The effectiveness of COCACOLA is demonstrated in both simulated and real datasets in comparison with state-of-art binning approaches such as CONCOCT, GroopM, MaxBin and MetaBAT. The superior performance of COCACOLA relies on two aspects. One is using L 1 distance instead of Euclidean distance for better taxonomic identification during initialization. More importantly, COCACOLA takes advantage of both hard clustering and soft clustering by sparsity regularization. In addition, the COCACOLA framework seamlessly embraces customized knowledge to facilitate binning accuracy. In our study, we have investigated two types of additional knowledge, the co-alignment to reference genomes and linkage of contigs provided by paired-end reads, as well as the ensemble of both. We find that both co-alignment and linkage information further improve binning in the majority of cases. COCACOLA is scalable and faster than CONCOCT, GroopM, MaxBin and MetaBAT. Availability and implementation: The software is available at https://github.com/younglululu/COCACOLA . Contact: fsun@usc.edu. Supplementary information: Supplementary data are available at Bioinformatics online. PMID- 27256314 TI - RANKS: a flexible tool for node label ranking and classification in biological networks. AB - RANKS is a flexible software package that can be easily applied to any bioinformatics task formalizable as ranking of nodes with respect to a property given as a label, such as automated protein function prediction, gene disease prioritization and drug repositioning. To this end RANKS provides an efficient and easy-to-use implementation of kernelized score functions, a semi-supervised algorithmic scheme embedding both local and global learning strategies for the analysis of biomolecular networks. To facilitate comparative assessment, baseline network-based methods, e.g. label propagation and random walk algorithms, have also been implemented. AVAILABILITY AND IMPLEMENTATION: The package is available from CRAN: https://cran.r-project.org/ The package is written in R, except for the most computationally intensive functionalities which are implemented in C. CONTACT: valentini@di.unimi.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27256313 TI - CART-a chemical annotation retrieval toolkit. AB - MOTIVATION: Data on bioactivities of drug-like chemicals are rapidly accumulating in public repositories, creating new opportunities for research in computational systems pharmacology. However, integrative analysis of these data sets is difficult due to prevailing ambiguity between chemical names and identifiers and a lack of cross-references between databases. RESULTS: To address this challenge, we have developed CART, a Chemical Annotation Retrieval Toolkit. As a key functionality, it matches an input list of chemical names into a comprehensive reference space to assign unambiguous chemical identifiers. In this unified space, bioactivity annotations can be easily retrieved from databases covering a wide variety of chemical effects on biological systems. Subsequently, CART can determine annotations enriched in the input set of chemicals and display these in tabular format and interactive network visualizations, thereby facilitating integrative analysis of chemical bioactivity data. AVAILABILITY AND IMPLEMENTATION: CART is available as a Galaxy web service (cart.embl.de). Source code and an easy-to-install command line tool can also be obtained from the web site. CONTACT: bork@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27256315 TI - SETH detects and normalizes genetic variants in text. AB - : Descriptions of genetic variations and their effect are widely spread across the biomedical literature. However, finding all mentions of a specific variation, or all mentions of variations in a specific gene, is difficult to achieve due to the many ways such variations are described. Here, we describe SETH, a tool for the recognition of variations from text and their subsequent normalization to dbSNP or UniProt. SETH achieves high precision and recall on several evaluation corpora of PubMed abstracts. It is freely available and encompasses stand-alone scripts for isolated application and evaluation as well as a thorough documentation for integration into other applications. AVAILABILITY AND IMPLEMENTATION: SETH is released under the Apache 2.0 license and can be downloaded from http://rockt.github.io/SETH/ CONTACT: thomas@informatik.hu berlin.de or leser@informatik.hu-berlin.de. PMID- 27256316 TI - Reaction electronic flux and its role in DNA intramolecular proton transfers. AB - Proton transfer reactions present a key step in many biological and chemical processes. Here, we focused on the electronic changes in the proton transfer reactions of the four DNA bases. In combination with the previous structural analysis the reaction electronic flux together with local descriptors as the Hirshfeld-I charges allow us to identify chemical events and rationalize the underlying reaction mechanism. Our results show that imine-enamine in adenine and citosyne, and keto-enol tautomerizations in thymine and guanine have different reaction mechanisms. The former involve net structural rearrangements driven by favoured electrostatic interactions between the proton and the acceptor atom whereas the keto-enol tautomerizations require electronic changes reflected in the reaction electronic flux and changes in the NBO bond orders which favour the proton transfer reaction. PMID- 27256317 TI - Is there still a place for erythrocyte sedimentation rate and C-reactive protein in systemic lupus erythematosus? AB - The inflammatory response during systemic lupus erythematosus (SLE) flares is known to be atypical, characterized by a disproportionately lower C-reactive protein (CRP) elevation when compared with erythrocyte sedimentation rate (ESR). Thus, in these patients, the analysis of inflammatory markers might be challenging in daily clinical practice. Clinicians need frequently to distinguish lupus reactivations and infectious conditions, and the significance of ESR and CRP seems to be different. Even though a non-specific marker of inflammation, ESR utility in SLE should not be neglected and it appears to be a useful biomarker for SLE activity assessment. Describing a specific cut-off for ESR in SLE is important for patients' follow-up, and levels up to 25-30 mm/h have been proposed as an upper limit of the normal range. Regarding CRP, even though higher baseline levels are described in SLE when compared with controls, including in remission periods, its response during flares seems to be incomplete and not always correlated with disease activity; while CRP values greater than 10 mg/l could be indicative for severe flares, when there is no serositis or arthritis, higher CRP levels above 50-60 mg/l may be associated with infection. PMID- 27256319 TI - Possible evidence for contribution of arbuscular mycorrhizal fungi (AMF) in phytoremediation of iron-cyanide (Fe-CN) complexes. AB - Arbuscular mycorrhizal fungi (AMF) are integral functioning parts of plant root systems and are widely recognized for enhancing contaminants uptake and metabolism on severely disturbed sites. However, the patterns of their influence on the phytoremediation of iron-cyanide (Fe-CN) complexes are unknown. Fe-CN complexes are of great common interest, as iron is one of the most abundant element in soil and water. Effect of ryegrass (Lolium perenne L.) roots inoculation, using mycorrhizal fungi (Rhizophagus irregularis and a mixture of R. irregularis, Funneliformis mosseae, Rhizophagus aggregatus, and Claroideoglomus etunicatum), on iron-cyanide sorption was studied. Results indicated significantly higher colonization of R. irregularis than the mixture of AMF species on ryegrass roots. Series of batch experiments using potassium hexacyanoferrate (II) solutions, in varying concentrations revealed significantly higher reduction of total CN and free CN content in the mycorrhizal roots, indicating greater cyanide decrease in the treatment inoculated with R. irregularis. Our study is a first indication of the possible positive contribution of AM fungi on the phytoremediation of iron-cyanide complexes. PMID- 27256320 TI - Corrigendum to "Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure" [Behav. Brain Res. 286 (2015) 201-211]. PMID- 27256318 TI - Oxidative stress induced in Hyalella azteca by an effluent from a NSAID manufacturing plant in Mexico. AB - Production in the pharmaceutical industry has increased and along with it, the amount of wastewater of various characteristics and contaminant concentrations. The main chemicals in these effluents are solvents, detergents, disinfectants such as sodium hypochlorite (NaClO)-and pharmaceutical products, all of which are potentially ecotoxic. Therefore, this study aimed to evaluate the oxidative stress induced in the amphipod Hyalella azteca by the effluent from a nonsteroidal anti-inflammatory drug (NSAID)-manufacturing plant. The median lethal concentration (72 h-LC50) was determined and H. azteca were exposed to the lowest observed adverse effect level (0.0732 %) for 12, 24, 48 and 72 h, and biomarkers of oxidative stress were evaluated [hydroperoxide content (HPC), lipid peroxidation (LPX), protein carbonyl content (PCC), and the activity of the superoxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)]. Statistically significant increases with respect to the control group (P < 0.05) were observed in HPC, LPX and PCC in H. azteca at all exposure times. Antioxidant enzymes activity SOD, CAT and GPx activity also increased significantly (P < 0.05) with respect to the control group. In conclusion, the industrial effluent analyzed in the present study contains NSAIDs and NaClO, and induces oxidative stress in H. azteca. PMID- 27256321 TI - Incidence of human papillomavirus contamination of transvaginal probes in Japan and possible contamination prevention strategy. AB - PURPOSE: To clarify the present status of human papillomavirus (HPV) contamination of transvaginal probes in Japan and propose a preventive method. METHODS: This study was performed at three institutes: a tertiary center, secondary hospital, and primary facility. To identify contamination rates, probes were disinfected and covered with probe covers and condoms; the cover was changed for each patient. The probes were tested for HPV, and those with HPV detected were analyzed to identify the type of HPV. Next, nurses put on new gloves before covering the probe for each patient, and the probes were similarly tested for HPV. RESULTS: A total of 120 probes were tested, and HPV was detected from a total of five probes, a contamination rate of 4.2 % (5/120). HPV was detected in all three institutes. Importantly, high-risk HPV, i.e., HPV-52, 56, and 59, was detected. After the "glove change strategy" was implemented, HPV was not detected on any of 150 probes tested at any of the three institutions. CONCLUSIONS: In Japan, the HPV contamination rate of vaginal probes in routine practice was 4.2 %. There was no HPV contamination of probes after changing the gloves for cover exchange for each patient. This strategy may prevent HPV probe contamination. PMID- 27256322 TI - Pseudo-asymmetry of cerebral blood flow in arterial spin labeling caused by unilateral fetal-type circle of Willis: Technical limitation or a way to better understanding physiological variations of cerebral perfusion and improving arterial spin labeling acquisition? AB - In the recently published article, "Unilateral fetal-type circle of Willis anatomy causes right-left asymmetry in cerebral blood flow with pseudo-continuous arterial spin labeling: A limitation of arterial spin labeling-based cerebral blood flow measurements?", it was shown by the method of arterial spin labeling (ASL) that unilateral fetal-type circle of Willis could induce variation of blood flow in cerebellar and posterior cerebral artery territory. We believe that the reported observation, rather than being a limitation, gives several interesting cues for understanding the ASL sequence. In this commentary, we formulate some suggestions regarding the use of ASL in clinical practice, discuss the potential causes of the above-mentioned pseudo-asymmetry and consider future improvements of the ASL technique. PMID- 27256323 TI - Baseline collateral status and infarct topography in post-ischaemic perilesional hyperperfusion: An arterial spin labelling study. AB - Focal hyperperfusion after acute ischaemic stroke could be of prognostic value depending upon its spatial localisation and temporal dynamics. Factors associated with late stage (12-24 h) perilesional hyperperfusion, identified using arterial spin labelling, are poorly defined. A prospective cohort of acute ischaemic stroke patients presenting within 4.5 h of symptom onset were assessed with multi modal computed tomography acutely and magnetic resonance imaging at 24 +/- 8 h. Multivariate logistic regression analysis and receiver operating characteristics curves were used. One hundred and nineteen hemispheric acute ischaemic stroke patients (mean age = 71 +/- 12 years) with 24 h arterial spin labelling imaging were included. Forty-two (35.3%) patients showed perilesional hyperperfusion on arterial spin labelling at 24 h. Several factors were independently associated with perilesional hyperperfusion: good collaterals (71% versus 29%, P < 0.0001; OR = 5, 95% CI = [1.6, 15.7], P = 0.005), major reperfusion (81% versus 48%, P = < 0.0001; OR = 7.5, 95% CI = [1.6, 35.1], P = 0.01), penumbral salvage (76.2% versus 47%, P = 0.002; OR = 6.6, 95% CI = [1.8, 24.5], P = 0.004), infarction in striatocapsular (OR = 9.5, 95% CI = [2.6, 34], P = 0.001) and in cortical superior division middle cerebral artery (OR = 4.7, 95% CI = [1.4, 15.7], P = 0.012) territory. The area under the receiver operating characteristic curve was 0.91. Our results demonstrate good arterial collaterals, major reperfusion, penumbral salvage, and infarct topographies involving cortical superior middle cerebral artery and striatocapsular are associated with perilesional hyperperfusion. PMID- 27256324 TI - Detection of RNA-DNA association by a proximity ligation-based method. AB - We describe a proximity ligation assay (PLA)-based method of assessing association of DNA and RNA in single cells during the cell cycle. Pulse-labeling of DNA with EdU and RNA with BrU and testing their close proximity by PLA demonstrates that RNA synthesis in individual cells resumes about 30-45 min after DNA replication. Consistent with this conclusion, RNA Pol II phosphorylated at Ser2 of its CTD is detected at the same time as RNA transcripts on nascent DNA. Our results also show that RNA is associated with DNA foci during all stages of mitosis. PMID- 27256325 TI - Modeling adsorption with lattice Boltzmann equation. AB - The research of adsorption theory has recently gained renewed attention due to its critical relevance to a number of trending industrial applications, hydrogen storage and shale gas exploration for instance. The existing theoretical foundation, laid mostly in the early twentieth century, was largely based on simple heuristic molecular interaction models and static interaction potential which, although being insightful in illuminating the fundamental mechanisms, are insufficient for computations with realistic adsorbent structure and adsorbate hydrodynamics, both critical for real-life applications. Here we present and validate a novel lattice Boltzmann model incorporating both adsorbate-adsorbate and adsorbate-adsorbent interactions with hydrodynamics which, for the first time, allows adsorption to be computed with real-life details. Connection with the classic Ono-Kondo lattice theory is established and various adsorption isotherms, both within and beyond the IUPAC classification are observed as a pseudo-potential is varied. This new approach not only enables an important physical to be simulated for real-life applications, but also provides an enabling theoretical framework within which the fundamentals of adsorption can be studied. PMID- 27256328 TI - Most government departments do not keep track of research they commission, inquiry finds. PMID- 27256326 TI - Field synopsis and meta-analyses of genetic epidemiological evidence for Kashin Beck disease, an endemic osteoarthropathy in China. AB - Kashin-Beck disease (KBD) is a chronic degenerative osteoarthropathy with unclear etiology. To provide current evidence supporting a genetic predisposition for KBD, we conducted a systematic review and meta-analysis of published literature on the genetic epidemiology of KBD. The PubMed, China National Knowledge Infrastructure and Wan Fang Data were searched up to August 2015 for articles published in English and Chinese. Genome-wide and exome sequencing, linkage, and case-control association studies for any genetic variants associated with KBD were included. Meta-analysis was performed for all single nucleotide polymorphisms (SNPs) that were evaluated in two or more studies. The effect size was summarized as odds ratios (ORs) with 95 % confidence intervals (CIs) by fixed and random effects models. A total of 24 articles were systematically reviewed. Eleven short tandem repeats on chromosomes 2, 11 and 12, 34 SNPs in 12 genes, as well as copy number variant 452 were identified as KBD susceptibility factors in individual studies. The meta-analysis of the GPX1 rs1050450, DIO2 rs225014, TrxR2 rs5748469 and HLA-DRB1 rs7745040 failed to reveal any associations with KBD. However, the meta-analysis of HLA-DRB1 rs9275295 allele A was associated with KBD (OR = 1.737, 95 % CI: 1.002-3.012). In addition, seven haplotypes in GPX1, GPX4, HLA-DRB1 and GDF5 genes also showed significant associations with KBD. In conclusions, our study could identify a number of genetic markers associated with KBD. However, the evidence does not currently support a strong association between the specific variants and KBD because of the limited number of studies, and in the future, more rigorous studies are needed to confirm KBD's links with these variants. PMID- 27256329 TI - Repetitive formation of optically-observable planar lipid bilayers by rotating chambers on a microaperture. AB - Optical observation of a planar lipid bilayer is an effective method of lipid bilayer characterization. However, previous methods for optically observable lipid bilayer formation are unsuitable for repetitive formation of lipid bilayers. In this paper, we propose a system that facilitates repetitive formation of horizontal lipid bilayers via mechanical rotation of the rotating part. We show that multiple bilayers can be observed within a short period, and that the electrical and optical characteristics of a bilayer can be analyzed simultaneously. PMID- 27256327 TI - A comparative transcriptome analysis of two sets of backcross inbred lines differing in lint-yield derived from a Gossypium hirsutum * Gossypium barbadense population. AB - Upland cotton (Gossypium hirsutum L.) is the most important fiber crop, and its lint-yield improvement is impeded due to its narrow genetic base and the lack of understanding of the genetic basis of yield. Backcross inbred lines (BILs) or near-isogenic lines (NILs) in the same genetic background differing in lint yield, developed through advanced backcrossing, provide an important genomic resource to study the molecular genetic basis of lint yield. In the present study, a high-yield (HY) group and a low-yield (LY) group each with three BILs were selected from a BIL population between G. hirsutum and G. barbadense. Using a microarray-based comparative transcriptome analysis on developing fibers at 10 days post-anthesis (DPA) between the two groups, 1486 differentially expressed genes (DEGs) were identified. A total of 212 DEGs were further mapped in the regions of 24 yield QTL and 11 yield trait QTL hotspots as reported previously, and 81 DEGs mapped with the 7 lint-yield QTL identified in the BIL population from which the two sets of BILs were selected. Gene Ontology annotations and Blast-Mapping-Annotation-KEGG analysis via Blast2GO revealed that more DEGs were associated with catalytic activity and binding, followed by transporters, nucleic acid binding transcription factors, structural molecules and molecular transducer activities. Six DEGs were chosen for a quantitative RT-PCR assay, and the results were consistent with the microarray analysis. The development of DEGs-based markers revealed that 7 single strand conformation polymorphism-based single nucleotide polymorphic (SSCP-SNP) markers were associated with yield traits, and 3 markers with lint yield. In the present study, we identified a number of yield and yield component QTL-co-localizing DEGs and developed several DEG-based SSCP SNP markers for the traits, thereby providing a set of candidate genes for molecular breeding and genetic manipulation of lint yield in cotton. PMID- 27256331 TI - A rare pulmonary hamartoma: fibroleiomyomatous hamartoma. AB - Pulmonary hamartomas are more common than expected because they are usually asymptomatic and are either discovered on routine chest radiography or when they are noted incidentally in approximately 0.25 % of autopsies. In contrast, pulmonary fibroleiomyomatous hamartoma, which consists of interlacing bundles of smooth muscle cells admixed with fibrous tissue and numerous tubular or cleft like epithelial inclusions, is a rare type of hamartoma. Controversy exists regarding the pathogenesis of this tumor. We herein present a rare case of a 68 year-old male patient without a pre-existing smooth muscle tumor, who underwent resection for a tumor that was considered to be a true pulmonary fibroleiomyomatous hamartoma. PMID- 27256332 TI - Flap revascularization in patients following immediate reconstruction using an autologous free dermal fat graft for breast cancer: a report of two cases. AB - It has been reported that use of the free dermal fat graft (FDFG) technique produces a good cosmetic outcome for breast cancer. An FDFG is harvested from the lower abdomen as a columnar-shaped specimen and implanted into the defect of the breast after a partial mastectomy as a volume replacement technique. In this report, two patients who underwent breast-conserving surgery with immediate reconstruction using an autologous FDFG are described in order to show the difference in status between one case with and one without blood flow in the graft. To assess the benefit of this technique using FDFGs, their cosmetic satisfaction was evaluated using a questionnaire, graft shrinkage was measured by CT, and blood flow was assessed using contrast-enhanced ultrasound (CEUS). Both patients scored 10 of 12 points on the questionnaire. After 2 years, shrinkage of the grafts was 21.6 and 25.2 %, respectively. Although one patient had no blood flow in the center of the graft, the other had blood flow from the pectoralis major muscle to the center of the graft. While satisfaction and graft shrinkage were similar in the two patients, one case showed blood flow and had a somewhat softer graft than the other. The graft status was maintained with a good cosmetic outcome for 3 years after breast-conserving surgery with immediate reconstruction using an autologous FDFG, despite mild shrinkage and hardness of the graft. It is notable that blood flow was observed into the graft on CEUS, and more distinct perfusion was seen in the softer graft case after more than 3 years. PMID- 27256330 TI - Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups. AB - Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups. PMID- 27256333 TI - Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure. AB - : Osteogenesis imperfecta (OI) is characterized by a high fracture rate and great heterogeneity. This cross-sectional study presents skeletal investigations and protein analyses in 85 adult OI patients. We find significant differences in bone mass, architecture, and fracture rate that correlate well with the underlying biochemical and molecular abnormalities. INTRODUCTION: OI is a hereditary disease characterized by compromised connective tissue predominantly caused by mutations in collagen type 1 (COL-1) encoding genes. Widespread symptoms reflect the ubiquity of COL-1 throughout the body. The purpose of this study was to improve our understanding of clinical manifestations by investigating anthropometry and skeletal phenotypes (DXA, HRpQCT) in an adult OI population and compare the findings to underlying COL-1 genotype and structure. METHODS: The study comprised 85 OI patients aged 45 (19-78) years, Sillence type I (n = 58), III (n = 12), and IV (n = 15). All patients underwent DXA, HRpQCT, spine X-ray, biochemical testing, and anthropometry. COL1A1 and COL1A2 were sequenced and 68 OI causing mutations identified (46 in COL1A1, 22 in COL1A2). Analysis of COL-1 structure (quantitative/qualitative defect) by SDS-PAGE was performed in a subset (n = 67). RESULTS: A qualitative collagen defect predisposed to a more severe phenotype with reduced aBMD, more fractures, and affected anthropometry compared to patients with a quantitative COL-1 defect (p < 0.05). HRpQCT revealed significant differences between patients with OI type I and IV. Patients with type I had lower vBMD (p < 0.005), thinner cortexes (p < 0.001), and reduced trabecular number (p < 0.005) compared to patients with type IV indicating that HRpQCT may distinguish type I from type IV better than DXA. CONCLUSION: The defective collagen in patients with OI has pronounced effects on the skeleton. The classical OI types based on the clinical classification show profound differences in bone mass and architecture and the differences correlate well with the underlying biochemical and molecular collagen abnormalities. PMID- 27256334 TI - Thigh abscess and necrotizing fasciitis following an inside-out transobturator tape intervention: a case report. AB - BACKGROUND: Tension-free vaginal transobturator tapes are used worldwide in the treatment of urinary incontinence in women. Very few severe complications have been described following this procedure, with no standard treatment yet established. CASE PRESENTATION: We present the case of a 36-year-old French white woman with no remarkable medical history, presenting with an abscess and necrotizing fasciitis 48 hours after an inside-out tension-free transobturator procedure. Samples were collected by guided puncture from the abscess, retrieving Staphylococcus aureus and Citrobacter koseri. CONCLUSIONS: Severe complications following this procedure are rare, although it can have the potential for significant morbidity and even mortality, which is worth highlighting. We recommend early surgical treatment in combination with broad-spectrum antibiotics and coverage for Staphylococcus aureus, which may be a causative agent. PMID- 27256335 TI - Experiences and preferences of care among Swedish immigrants following a prenatal diagnosis of congenital heart defect in the fetus: a qualitative interview study. AB - BACKGROUND: Immigrants experience significant challenges when in contact with healthcare and report less satisfaction with maternity care compared to native Swedes. Research that gives voice to pregnant immigrant women and their partners following a prenatal diagnosis of a fetal anomaly is scarce. Thus, the aim of this study was to explore experiences and preferences of care following a prenatal diagnosis of congenital heart defect among Swedish immigrants. METHODS: Pregnant immigrants and their partners were consecutively recruited following a prenatal diagnosis of a congenital heart defect in the fetus. Nine respondents were interviewed in five interviews, four with the aid of a professional interpreter. The material was analyzed using manifest qualitative content analysis. RESULTS: The analysis resulted in five categories: 1) "Trustworthy information", 2) "Language barriers", 3) "Psychosocial situation", 4) "Peer support", and 5) "Religious positions". CONCLUSION: The potential need for interpreter services, visual information, psychosocial support, coordination with welfare officers, and respect for religious positions about termination of pregnancy are all important aspects for health professionals to consider when consulting immigrants faced with a prenatal diagnosis of fetal anomaly in the fetus. Peer support within this context needs to be further explored in future studies. PMID- 27256336 TI - Effect of Insulin and Metformin Combination Treatment on Colon Adenoma and Advanced Adenoma Among DM II. AB - BACKGROUND: The risk for colorectal adenoma and advanced adenoma among diabetes mellitus II (DM II) has been debated to differ with the type of anti-diabetic therapy. Insulin increases whereas metformin decreases the risk for colon adenoma (Ad) and advanced Ad (AAd). There have been no studies to evaluate the effect of combination treatment with insulin and metformin on colon Ad and AAd. METHODS: The retrospective study included DM II patients undergoing screening colonoscopy. Subjects with incomplete colonoscopy, poor bowel preparation, personal history of colorectal cancer (CRC)/inflammatory bowel disease/hereditary nonpolyposis colorectal cancer/familial adenomatosis polyposis/colectomy or family history of CRC were excluded. Subjects were categorized into group 1 (insulin only), group 2 (metformin only), group 3 (combination of insulin and metformin) and group 4 (miscellaneous). Group 4 was excluded from data analysis. Ad detection rate (ADR) and advanced ADR (AADR) were calculated for each group. RESULTS: Three hundred thirty-nine subjects composed the study group, with a mean age of 60.0 years and male to female ratio of 1:1.4. Composite ADR and AADR for study population was 35.1 and 15.3 %, respectively. Groups 1, 2 and 3 were composed of 88 (26.0 %), 211 (62.2 %) and 40 (11.8 %) subjects, respectively. ADR for groups 1, 2 and 3 was 40.9, 33.2 and 32.5 %, respectively (p value = 0.413). AADR for groups 1, 2 and 3 was 18.2, 15.2 and 10.0 %, respectively (p value = 0.489). CONCLUSION: A decremental trend was observed in ADR and AADR across group 1, group 2 and group 3 (p value >0.05). PMID- 27256337 TI - Time Flies: an Examination of Genetic Counselor Professional Development: Introduction to Special Issue on Genetic Counselor Development. PMID- 27256338 TI - Using the angiogenic factors sFlt-1 and PlGF with Doppler ultrasound of the uterine artery for confirming preeclampsia. AB - PURPOSE: The aim of this study is to assess the value of the angiogenic factors for diagnosing preeclampsia and predicting the severity of manifestation. A secondary aim is assessing the combination of the uterine artery Doppler with the angiogenic factors for improving the diagnostic power. METHODS: This is a prospective single center study in a tertiary referral hospital. This study includes 728 individual patients. Inclusion criteria were singleton pregnancies, a referral to the hospital with suspicion of preeclampsia and any one or combination of the following symptoms: headache, upper abdominal pain, edema, and hypertension. Patients with complications that would affect the course of the pregnancy, such as placenta praevia, premature preterm rupture of membranes, breech presentation, and fetal chromosomal or structural anomalies, were excluded from the study. Blood samples collection and uterine artery Doppler ultrasound were performed at time of recruitment. The differences in sFlt-1, PlGF, and their quotient among normal collective and patients with preeclampsia were analyzed. Doppler ultrasound was performed by one of four highly qualified sonographers. Wilcoxon-Mann-Whitney U test, Spearman's rank correlation, receiver operating characteristic curves, Chi-square test, and logistic regression were used in the analysis. RESULTS: A total of 1003 individual samples for the angiogenic factors were included in the analysis. 584 out of the recruited 728 patients had follow up data with delivery information at the study hospital. Patients with preeclampsia show a significant increase in sFlt-1, which directly correlate with the increased severity of manifestation (Spearman's rho 0.49). The sFlt-1 cut-off value of 5424 pg/ml confirms preeclampsia with 83.7 % sensitivity, 68.1 % specificity, and 24 % misclassification rate. Preeclampsia patients also show a significant decrease in PlGF, which negatively correlates with the increased severity of manifestation (Spearman's rho -0.39). A PlGF cut-off value of 118 pg/ml confirms preeclampsia with 47.6 % sensitivity, 71.4 % specificity, and 27 % misclassification rate. Logistic regression shows that a combination of the quotient from sFlt-1/PlGF with notching and uterine artery PI provides a valid model for diagnosing preeclampsia with a diagnostic power of 74.4 %. CONCLUSIONS: The study confirms the use of the sFlt-1 and PlGF for diagnosing preeclampsia. It also shows their significance in differentiating between different categories of preeclampsia according to severity. This study shows that the use of angiogenic factors in combination with ultrasound findings provides valid models for confirming preeclampsia. PMID- 27256339 TI - Comparison of seroma production in breast conserving surgery with or without intraoperative radiotherapy as tumour bed boost. AB - INTRODUCTION: One of the most common complications in breast conserving surgery is seroma formation. The origin of seroma formation remains unclear. While intraoperative radiotherapy (IORT) has been shown to be an alternative to whole breast irradiation, the influence on seroma production is unclear. Therefore, this analysis compares seroma production in patients with breast conserving surgery with or without IORT as tumour bed boost during breast conserving surgery. METHOD: A retrospective analysis of seroma production in patients with nodal-negative (pN0sn) pT1/2 primary breast cancer treated between September 2010 and October 2013 at the Breast Cancer Centre, University Hospital Ulm was performed. Patients with neoadjuvant chemotherapy, previous breast/axillary surgery or more than one intervention were excluded. IORT was applied as a tumour bed boost with 50-kV X-rays (Intra beam((r))) delivering 9 Gy at the applicator surface. Seroma formation was measured using wound drains placed in breast and in axilla. RESULTS: Data of 152 patients (99 -IORT; 53 +IORT) were available for analysis. No significant differences between patients with or without IORT with regard to seroma production and number of days until drain removal were found (all p > 0.05). CONCLUSION: Patients with IORT encountered no increased seroma production and removal of the drains was not delayed compared to patients with breast conserving surgery only. Our results indicate that IORT does not increase the seroma production compared to surgery alone. PMID- 27256340 TI - Minimally invasive, endoscopic Achilles tendon reconstruction using semitendinosus and gracilis tendons with Endobutton stabilization. AB - BACKGROUND: Plantaris tendon, peronus brevis tendon and flexor hallucis longus tendon augmentation, commonly used in Achilles tendon rupture, often lead to weakening of injured foot and they require the immobilization after the surgery. It is essential to develop the technique, which gives no such limitation and allows for immediate functional improvement. METHODS: We present our method of minimally invasive, endoscopic Achilles tendon reconstruction using semitendinosus and gracilis tendons with Endobutton stabilization. RESULTS: Posterolateral and posteromedial portals were made approximately 3 cm above the posterosuperior part of the calcaneus to clean the area of the Achilles tendon endoscopically. Then the hamstrings are harvested and prepared for the "Endobutton" system. A midline incision of the skin is performed approximately 1 cm above the posterosuperior part of the calcaneus to approach to the posterosuperior part of the calcaneus. Then under fluoroscopy the calcaneus was drilled through using K-wire. The distal end of the graft equipped with an Endobutton loop was entered into the drilled tunnel in the calcaneus. Later, 8 consecutive skin incisions are performed. Proximal ends of the graft were brought out through the native Achilles tendon reaching medial and lateral skin incisions. The final step was to transfer and tie the graft ends through the most proximal skin incision. CONCLUSIONS: This minimally invasive, endoscopic technique allows reconstruction of the Achilles tendon using semitendinosus and gracilis tendons with Endobutton stabilization and can be used in so-called "difficult", resistant cases as a "salvage procedure". PMID- 27256341 TI - The use of anti-factor Xa monitoring in a selection of patients receiving enoxaparin at a large academic medical center. AB - Therapeutic enoxaparin is commonly used over heparin because of its favorable pharmacokinetic profile and ease of administration. Monitoring of the anticoagulant response, if necessary, is done with anti-factor Xa levels. Currently, it is suggested that monitoring may be beneficial in patients who are overweight and those with renal dysfunction. This study aimed to characterize the use of enoxaparin at a large-academic medical center in patients >150 kg, <45 kg and in those with renal dysfunction, and to describe the rate of anti-factor Xa monitoring in these patients. There were 273 patients included in the study: n = 96 for <45 kg arm, n = 111 for >150 kg arm and n = 66 for renal dysfunction arm. Less than 30 % of patients in each arm had low molecular weight heparin anti factor Xa levels drawn. Of these only half were drawn as peak levels (4 h post dose). Overall rates of anti-factor Xa monitoring was low. It was found that obese patients achieved therapeutic anticoagulation with lower than recommended doses; underweight patients were often subtherapeutic on the recommended doses; and patients with renal dysfunction tended to have therapeutic to subtherapeutic anti-factor Xa levels. Ultimately, this evaluation showed that enoxaparin has unpredictable pharmacokinetics in these three high-risk patient populations and anti-factor Xa monitoring may be necessary to ensure therapeutic levels and appropriate dosing. PMID- 27256344 TI - Shared Vision Among Acute Care Magnet(r) Hospital Nurses: Ordinal Confirmatory Factor Analysis. AB - Psychometric testing of the Shared Vision (SV) scale that measures team efforts toward common patient-centered goals was initially estimated among rural hospital nurse executives. The purpose of this study was to estimate the scale's reliability (internal consistency), convergent validity (Pearson correlation with Practice Environment Scale), and structural validity (ordinal confirmatory factor analysis) among acute care Magnet(r) hospital nurses. The study sample included 289 nurses from 27 acute care Magnet(r) hospitals. The scale demonstrated acceptable estimates for internal consistency (Cronbach's alpha = .902, 95% confidence interval [CI] = [0.883, 0.919]), convergent validity ( r = .720, p < .001), and structural validity with a one-factor structure. The findings of this study supported the reliability and validity of the SV scale as a unidimensional construct in measuring SV among nurses in acute care Magnet(r) hospitals. Further testing among different nursing providers and health care settings is needed to accumulate evidence and expand use of the instrument. PMID- 27256342 TI - Fibrin structure in organized thrombotic material removed during pulmonary artery endarterectormy: the effect of vessel calibre. AB - Pulmonary endarterectomy (PEA) is a curative therapeutic approach in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The location dependent structural differences of thrombotic material found in pulmonary arteries in CTEPH are poorly investigated. We present the case of a 47-year-old woman with antiphospholipid syndrome, diabetes mellitus and abnormal fibrin phenotype, who underwent PEA for CTEPH. Intravascular material removed bilaterally during PEA (from lobar, segmental and sub-segmental arteries) has been studied using light and scanning electron microscopy (SEM). Light microscopy showed tighter fibrous network in the portions of intraluminal thrombotic material facing the vessel wall, which contained collagen and fibrin fibers, and abundant cells. Cells, evaluated by immunostaining, were present in the whole removed material. Tissue factor expression was also observed with the highest values in the portions of intravascular material facing the vessel wall. In the main pulmonary arteries, SEM images revealed thick fibers of fibrous proteins loosly meshed and few erythrocytes and platelets between them (both dysmorphic "wedged" and fresh cells were present). In the fibrotic layers, containing mainly collagen and fibrin, removed from the lobar/segmental pulmonary arteries we found a stepwise increase in fiber density with decreasing vessel calibre, followed by denser fibrous networks composed of thinner fibers. Elastic fibers in the lobar and segmental arteries were aligned along the blood flow vector. These findings demonstrate differences in the structure of endarterectomized PEA material dependent on the vessel calibre and might contribute to understanding of CTEPH pathophysiology. PMID- 27256345 TI - Frequency of silent cerebral ischemia in patients with transfusion-dependent beta thalassemia major compared to healthy individuals. PMID- 27256343 TI - Pathways and gene networks mediating the regulatory effects of cannabidiol, a nonpsychoactive cannabinoid, in autoimmune T cells. AB - BACKGROUND: Our previous studies showed that the non-psychoactive cannabinoid, cannabidiol (CBD), ameliorates the clinical symptoms in mouse myelin oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune encephalomyelitis model of multiple sclerosis (MS) as well as decreases the memory MOG35-55-specific T cell (TMOG) proliferation and cytokine secretion including IL-17, a key autoimmune factor. The mechanisms of these activities are currently poorly understood. METHODS: Herein, using microarray-based gene expression profiling, we describe gene networks and intracellular pathways involved in CBD-induced suppression of these activated memory TMOG cells. Encephalitogenic TMOG cells were stimulated with MOG35-55 in the presence of spleen-derived antigen presenting cells (APC) with or without CBD. mRNA of purified TMOG was then subjected to Illumina microarray analysis followed by ingenuity pathway analysis (IPA), weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) elucidation of gene interactions. Results were validated using qPCR and ELISA assays. RESULTS: Gene profiling showed that the CBD treatment suppresses the transcription of a large number of proinflammatory genes in activated TMOG. These include cytokines (Xcl1, Il3, Il12a, Il1b), cytokine receptors (Cxcr1, Ifngr1), transcription factors (Ier3, Atf3, Nr4a3, Crem), and TNF superfamily signaling molecules (Tnfsf11, Tnfsf14, Tnfrsf9, Tnfrsf18). "IL-17 differentiation" and "IL-6 and IL-10-signaling" were identified among the top processes affected by CBD. CBD increases a number of IFN-dependent transcripts (Rgs16, Mx2, Rsad2, Irf4, Ifit2, Ephx1, Ets2) known to execute anti proliferative activities in T cells. Interestingly, certain MOG35-55 up-regulated transcripts were maintained at high levels in the presence of CBD, including transcription factors (Egr2, Egr1, Tbx21), cytokines (Csf2, Tnf, Ifng), and chemokines (Ccl3, Ccl4, Cxcl10) suggesting that CBD may promote exhaustion of memory TMOG cells. In addition, CBD enhanced the transcription of T cell co inhibitory molecules (Btla, Lag3, Trat1, and CD69) known to interfere with T/APC interactions. Furthermore, CBD enhanced the transcription of oxidative stress modulators with potent anti-inflammatory activity that are controlled by Nfe2l2/Nrf2 (Mt1, Mt2a, Slc30a1, Hmox1). CONCLUSIONS: Microarray-based gene expression profiling demonstrated that CBD exerts its immunoregulatory effects in activated memory TMOG cells via (a) suppressing proinflammatory Th17-related transcription, (b) by promoting T cell exhaustion/tolerance, (c) enhancing IFN dependent anti-proliferative program, (d) hampering antigen presentation, and (d) inducing antioxidant milieu resolving inflammation. These findings put forward mechanism by which CBD exerts its anti-inflammatory effects as well as explain the beneficial role of CBD in pathological memory T cells and in autoimmune diseases. PMID- 27256346 TI - Multiple cytokine-producing primary cutaneous anaplastic large cell lymphoma. PMID- 27256347 TI - Abdominal aortic thrombosis secondary to reactive thrombocytosis in a patient with iron deficiency anemia. PMID- 27256348 TI - Evaluation of bone mineral density in patients with hemoglobin H disease. AB - OBJECTIVES: This study was conducted to assess bone mineral density (BMD) and bone mineral content (BMC) of patients with hemoglobin H (HbH) disease. METHODS: BMD and BMC were measured by dual energy X-ray absorptiometry of the lumbar spines and femur neck in 21 patients with Hb H disease over the age of 10 years. An association of BMD with sex, age, hemoglobin, calcium, phosphorus, and serum ferritin level was also evaluated. RESULTS: Prevalence of BMD below the expected range for age in the lumbar spine and femur neck region in patients with HbH disease were 33.3 and 14.3 %, respectively. Lumbar BMD was significantly lower in the patients compared to healthy individuals (median (min-max) 0.725 (0.595 0.924) vs. 1.061 (0.645-1.238), P < 0.001)). There was no significant relationship between BMD in the lumbar and femur neck with any of the evaluated variables (P value >0.05). CONCLUSION: Data regarding bone density in HbH disease is limited; osteoporosis as a common complication of beta-thalassemia intermedia syndrome should be considered even in HbH which shows its prevalence is less than beta-thalassemia intermedia. PMID- 27256349 TI - Total Thyroidectomy versus Bilateral Subtotal Thyroidectomy for Bilateral Multinodular Nontoxic Goiter: A Meta-Analysis. AB - AIM: The aim of this meta-analysis is to assess and validate the feasibility and safety of total thyroidectomy (TT) when compared to bilateral subtotal thyroidectomy (BST) for bilateral multinodular nontoxic goiter (BMNG). MATERIALS AND METHODS: PubMed, Web of Knowledge, and Ovid's database were searched for studies published in English language between January 1990 and December 2014. A meta-analysis was performed to compare the complications and recurrences of TT versus BST. The search terms used were 'total thyroidectomy', 'bilateral subtotal thyroidectomy', 'multinodular nontoxic goiter' and 'randomized clinical trial'. The reference lists of relevant studies were checked manually to locate any missing studies. RESULTS: Four trials with a total of 1,078 patients were analyzed. Although the incidence of transient hypoparathyroidism was higher in TT than in BST (OR = 2.59, 95% CI [1.58-4.24], p = 0.0002), TT was associated with a significantly lower incidence of recurrence (OR = 0.04, 95% CI [0.01, 0.17], p < 0.0001). There were no statistically significant differences for the presence of transient/permanent recurrent laryngeal nerve palsy and permanent hypoparathyroidism between the two groups. CONCLUSION: TT is a feasible and safe procedure for patients with BMNG. Although TT involves a significantly higher risk of postoperative transient hypoparathyroidism, it has a lower recurrence rate than BST. PMID- 27256351 TI - Pertussis: History of the Disease and Current Prevention Failure. AB - Pertussis or whooping cough has been given many names over the centuries. It was first recognized in the Middle Ages and since then various epidemics have been described. Jules Bordet and Octave Gengou isolated Bordetella pertussis, a causative agent for whooping cough, in Paris more than 100 years ago, which created an excellent opportunity to invent a vaccine. In 1914 the whole-cell pertussis vaccine was invented, then in the 1940s it was combined with tetanus and diphtheria toxoids to become DTP and it became widely available. A successive decrease in the incidence of the disease has since been observed. The vaccine has been about 80 % effective in preventing serious disease and death from pertussis. The disadvantage is that the vaccine offers protection for 5-10 years after the last dose of the full vaccination course. The second issue is the question of how to prevent side effects of the whole-cell vaccine. In the 1990s, the acellular vaccine was introduced in the US and gradually replaced the whole-cell vaccine. About 10 years later, a possible failure with the new vaccine has been observed, that is a lack of long-term protection. Nowadays, both vaccines are used, with the acellular vaccine being vastly predominant in most developed countries. Pertussis incidence has increased since the 1980s, but new prevention strategies include booster doses for specific age groups. PMID- 27256350 TI - Predicting exercise capacity after lobectomy by single photon emission computed tomography and computed tomography. AB - OBJECTIVES: This study compared the prediction of postoperative exercise capacity by employing lung perfusion scintigraphy images obtained with single photon emission computed tomography together with computed tomography (SPECT/CT) versus the common method of counting subsegments (SC method). METHODS: In 18 patients scheduled for lobectomy, predicted postoperative maximum oxygen uptake per kilogram body weight ([Formula: see text]) was calculated by the SPECT/CT and SC methods. Correlations were examined between the [Formula: see text] predicted by SPECT/CT or the SC method, and the actual [Formula: see text] measured at 2 weeks (mean 15.4 +/- 1.5 days) and 1 month (mean 29.1 +/- 0.75 days) after surgery to determine whether SPECT/CT was more accurate than SC for predicting postoperative exercise capacity. RESULTS: There was a significant positive correlation between the [Formula: see text] predicted by SPECT/CT and the actual value at 2 weeks (r = 0.802, p < 0.0001) or 1 month (r = 0.770, p < 0.0001). There was also a significant positive correlation between the [Formula: see text] predicted by SC and the actual value at 2 weeks (r = 0.785, p < 0.0001) or 1 month (r = 0.784, p < 0.0001). CONCLUSIONS: This study showed that both SPECT/CT and the SC method were useful for predicting postoperative [Formula: see text] in the clinical setting. PMID- 27256352 TI - Oral glucocorticoid therapy and all-cause and cause-specific mortality in patients with rheumatoid arthritis: a retrospective cohort study. AB - Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias-a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81-2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose-response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death. PMID- 27256353 TI - The association between habitual physical activity and cigarette cravings, and influence of smokers' characteristics in disadvantaged smokers not ready to quit. AB - RATIONALE: Habitual physical activity (PA) may have an important role in suppressing cigarette cravings. Systematic reviews show a strong acute effect of bouts of PA on reducing cigarette cravings, and it may be that these effects accumulate. OBJECTIVES: The aim was to investigate the relationship between habitual levels of PA and cigarette cravings in disadvantaged smokers not ready to quit by examining baseline cross-sectional data from the Exercise Assisted Reduction then Stop smoking study (EARS). METHODS: A series of linear regression models were applied to investigate the relationship between habitual PA and cigarette cravings and to identify additional predictors of cigarette cravings. The analyses were extended by including interaction terms with PA to identify potential moderators of the relationship between PA and cravings. RESULTS: A higher level of moderate intensity PA was associated with lower cravings (p = 0.033). Additional predictors were the mood and physical symptoms scale (p = 0.007; higher scores were associated with higher cravings) and alcohol consumption (p = 0.002; higher consumption was associated with lower cravings). In addition, a moderation effect of alcohol consumption was found; at higher levels of alcohol consumption, higher PA was significantly associated with higher cravings (p = 0.023). CONCLUSIONS: Overall, participation in regular PA is associated with reduced cigarette cravings; among those with heavy alcohol consumption, this participation is associated with higher cravings. These exploratory analyses suggest that further research into the relationship between PA, alcohol consumption and cigarette cravings is needed. PMID- 27256354 TI - Effects of acute administration of the GABA(B) receptor agonist baclofen on behavioral flexibility in rats. AB - RATIONALE: The ability to adjust response strategies when faced with changes in the environment is critical for normal adaptive behavior. Such behavioral flexibility is compromised by experimental disruption of cortical GABAergic signaling, as well as in conditions such as schizophrenia and normal aging that are characterized by cortical hyperexcitability. The current studies were designed to determine whether stimulation of GABAergic signaling using the GABA(B) receptor agonist baclofen can facilitate behavioral flexibility. METHODS: Male Fischer 344 rats were trained in a set-shifting task in which they learned to discriminate between two response levers to obtain a food reward. Correct levers were signaled in accordance with two distinct response rules (rule 1: correct lever signaled by a cue light; rule 2: correct lever signaled by its left/right position). The order of rule presentation varied, but they were always presented sequentially, with the trials and errors to reach criterion performance on the second (set shift) rule providing the measure of behavioral flexibility. Experiments determined the effects of the GABA(B) receptor agonist baclofen (intraperitoneal, 0, 1.0, 2.5, and 4.0 mg/kg) administered acutely before the shift to the second rule. RESULTS: Baclofen enhanced set-shifting performance. Control experiments demonstrated that this enhancement was not simply due to improved discrimination learning, nor was it due to impaired recall of the initial discrimination rule. CONCLUSIONS: The results demonstrate that baclofen can facilitate behavioral flexibility, suggesting that GABA(B) receptor agonists may have utility for treating behavioral dysfunction in neuropsychiatric disorders. PMID- 27256355 TI - Poor sensitization of 50-kHz vocalization response to amphetamine predicts rat susceptibility to self-administration of the drug. AB - RATIONALE: Our previous studies showed promise for using sensitization of the frequency-modulated 50-kHz vocalization response to amphetamine (AMPH) as an index of rat vulnerability to AMPH addiction. OBJECTIVE: This study aimed to test the utility of sensitizing frequency-modulated (FM) 50-kHz vocalization in the AMPH self-administration paradigm as well as the ability of N-acetylcysteine to prevent self-administration relapse. METHODS: Rats were subjected to the so called two-injection protocol of sensitization (TIPS) using AMPH and were categorized as low-sensitized callers (LCTIPS) or high-sensitized callers (HCTIPS) based on the individual outcomes. Then, they were given 44 sessions of AMPH self-administration followed by a 17-session N-acetylcysteine-aided extinction course and a single session of AMPH-primed self-administration reinstatement. RESULTS: LCTIPS compared to HCTIPS rats showed no considerable difference in the FM 50-kHz vocalization rate during the self-administration training or extinction course, but they were considerably more likely to acquire AMPH self-administration and experience drug-induced reinstatement of this trait. Moreover, the LCTIPS rats were more likely than HCTIPS rats to have a markedly higher FM 50-kHz vocalization rate after AMPH reinstatement. N-acetylcysteine did not affect the course of self-administration extinction or the instrumental or FM 50-kHz vocalization responses to AMPH reinstatement. CONCLUSIONS: There is no link between the FM 50-kHz vocalization and key characteristics of AMPH self administration. Additionally, N-acetylcysteine does not help prevent AMPH self administration relapse. However, there is a high predictive value for poor sensitization of the FM 50-kHz vocalization response to AMPH with respect to the acquisition and maintenance of self-administration of this psychostimulant. PMID- 27256356 TI - Do blood plasma levels of oxytocin moderate the effect of nasally administered oxytocin on social orienting in high-functioning male adults with autism spectrum disorder? AB - OBJECTIVE: The study investigated whether baseline plasma oxytocin (OXT) concentrations might moderate the effects of nasally administered OXT on social orienting. METHODS: Thirty-one males with Autism spectrum disorder (ASD) and thirty healthy males participated in a double-blind placebo-controlled crossover trial. After administration of the compound, participants were viewing pictures from the International Affective Picture System that represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. The outcome measures were a cardiac evoked response (ECR) and a cortical evoked long latency parietal positivity (LPP). RESULTS: Males with ASD had significantly higher plasma baseline levels than the controls. In the absence of general treatment effects, higher baseline concentrations were found to be associated with larger treatment effects, particularly in the group of males with ASD. Higher post-treatment plasma OXT concentrations were found to be associated with smaller treatment effects and larger orienting responses in the placebo situation in the group of controls. CONCLUSIONS: We interpret our findings as suggesting that it is the central availability of OXT determining how much of the nasally administered OXT will become centrally absorbed and how much of it will become released into the bloodstream. PMID- 27256357 TI - Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing. AB - RATIONALE: Lithium remains the most effective treatment for bipolar disorder and also has important effects to lower suicidal behaviour, a property that may be linked to its ability to diminish impulsive, aggressive behaviour. The antioxidant drug, ebselen, has been proposed as a possible lithium-mimetic based on its ability in animals to inhibit inositol monophosphatase (IMPase), an action which it shares with lithium. OBJECTIVES: The aim of the study was to determine whether treatment with ebselen altered emotional processing and diminished measures of risk-taking behaviour. METHODS: We studied 20 healthy participants who were tested on two occasions receiving either ebselen (3600 mg over 24 h) or identical placebo in a double-blind, randomized, cross-over design. Three hours after the final dose of ebselen/placebo, participants completed the Cambridge Gambling Task (CGT) and a task that required the detection of emotional facial expressions (facial emotion recognition task (FERT)). RESULTS: On the CGT, relative to placebo, ebselen reduced delay aversion while on the FERT, it increased the recognition of positive vs negative facial expressions. CONCLUSIONS: The study suggests that at the dosage used, ebselen can decrease impulsivity and produce a positive bias in emotional processing. These findings have implications for the possible use of ebselen in the disorders characterized by impulsive behaviour and dysphoric mood. PMID- 27256359 TI - Label-Free Classification of Bax/Bak Expressing vs. Double-Knockout Cells. AB - We combine optical scatter imaging with principal component analysis (PCA) to classify apoptosis-competent Bax/Bak-expressing, and apoptosis resistant Bax/Bak null immortalized baby mouse kidney cells. We apply PCA to 100 stacks each containing 236 dark-field cell images filtered with an optically implemented Gabor filter with period between 0.3 and 2.9 MUm. Each stack yields an "eigencell" image corresponding to the first principal component obtained at one of the 100 Gabor filter periods used. At each filter period, each cell image is multiplied by (projected onto) the eigencell image. A Feature Matrix consisting of 236 * 100 scalar values is thus constructed with significantly reduced dimension compared to the initial dataset. Utilizing this Feature Matrix, we implement a supervised linear discriminant analysis and classify successfully the Bax/Bak-expressing and Bax/Bak-null cells with 94.7% accuracy and an area under the curve (AUC) of 0.993. Applying a feature selection algorithm further reveals that the Gabor filter period ranges most significant for the classification correspond to both large (likely nuclear) features as well as small sized features (likely organelles present in the cytoplasm). Our results suggest that cells with a genetic defect in their apoptosis pathway can be differentiated from their normal counterparts by label-free multi-parametric optical scatter data. PMID- 27256358 TI - Responses to drugs of abuse and non-drug rewards in leptin deficient ob/ob mice. AB - RATIONALE: Although leptin receptors are found in hypothalamic nuclei classically associated with homeostatic feeding mechanisms, they are also present in brain regions known to regulate hedonic-based feeding, natural reward processing, and responses to drugs of abuse. The ob/ob mouse is deficient in leptin signaling, and previous work has found altered mesolimbic dopamine signaling and sensitivity to the locomotor activating effects of amphetamine in these mice. OBJECTIVES: We directly assessed responses to three drugs of abuse and non-drug rewards in the leptin-deficient ob/ob mouse. METHODS: Ob/ob mice were tested in assays of sweet preference, novelty seeking, and drug reward/reinforcement. RESULTS: In assays of novelty seeking, novel open field activity and operant sensation seeking were reduced in ob/ob mice, although novel object interaction and novel environment preference were comparable to wild types. We also found that ob/ob mice had specific phenotypes in regard to cocaine: conditioned place preference for 2.5 mg/kg was increased, while the locomotor response to 10 mg/kg was reduced, and cocaine self-administration was the same as wild types. Ob/ob mice also acquired self-administration of the potent opioid remifentanil, but breakpoints for the drug were significantly reduced. Finally, we found significant differences in ethanol drinking in ob/ob mice that correlated negatively with body weight and positively with operant sensation seeking. CONCLUSIONS: In conclusion, ob/ob mice displayed task-specific deficits in novelty seeking and dissociable differences in reward/reinforcement associated with cocaine, remifentanil, and ethanol. PMID- 27256360 TI - Biomechanical Properties and Microstructure of Heart Chambers: A Paired Comparison Study in an Ovine Model. AB - Mechanical properties of the cardiac tissue play an important role in normal heart function. The goal of this study was to determine the passive mechanical properties of all heart chambers through a paired comparison study in an ovine model. Ovine heart was used due its physiological and anatomical similarities to human heart. A total of 189 specimens from anterior and posterior portions of the left and right ventricles, atria, and appendages underwent biaxial mechanical testing. A Fung-type strain energy function was used to fit the experimental data. Tissue behavior was quantified based on the magnitude of strain energy, as indicator of tissue stiffness, at equibiaxial strains of 0.10, 0.15, and 0.20. Statistical analysis revealed no significant difference in strain energy storage between anterior and posterior portions of each chamber, except for the right ventricle where strain energy storage in the posterior specimens were higher than the anterior specimens. Additionally, all chambers from the left side of the heart had significantly higher strain energy storage than the corresponding chambers on the right side. Furthermore, the highest to lowest stored strain energy were associated with ventricles, appendages, and atria, respectively. Microstructure of tissue specimens from different chambers was also compared using histology. PMID- 27256361 TI - The Distinct Effects of Estrogen and Hydrostatic Pressure on Mesenchymal Stem Cells Differentiation: Involvement of Estrogen Receptor Signaling. AB - This study aimed to investigate the differential and synergistic effects of mechanical stimulation and estrogen on the proliferation and osteogenic or chondrogenic differentiation potential of bone marrow mesenchymal stem cells (BMSCs) and the roles of estrogen receptor (ER) in them. BMSCs were isolated and cultured using the whole bone marrow adherence method, and flow cytometry was used to identify the surface marker molecules of BMSCs. Cells were pre-treated with 1 nM 17beta-estradiol or 1 nM of the estrogen receptor antagonist tamoxifen. Then, the cells were stimulated with hydrostatic pressure. Assessment included flow cytometry analysis of the cell cycle; immunofluorescent staining for F actin; protein quantification for MAPK protein; and mRNA analysis for Col I, OCN, OPN and BSP after osteogenic induction and Sox-9, Aggrecan and Col-II after chondrogenic induction. Hydrostatic pressure (90 kPa/1 h) and 1 nM 17beta estradiol enhanced the cellular proliferation ability and the cytoskeleton activity but without synergistic biological effects. Estrogen activated ERKs and JNKs simultaneously and promoted the osteogenic differentiation, whereas the pressure just caused JNK-1/2 activation and promoted the chondrogenic differentiation of BMSCs. Estrogen had antagonism effect on chondrogenic promotion of hydrostatic pressure. Mechanobiological effects of hydrostatic pressure are closely associated with ERalpha activity. MAPK molecules and F-actin were likely to be important mediator molecules in the ER-mediated mechanotransduction of BMSCs. PMID- 27256362 TI - Micro-structural and Biaxial Creep Properties of the Swine Uterosacral-Cardinal Ligament Complex. AB - The uterosacral ligament and cardinal ligament (USL/CL) complex is the major suspensory tissue of the uterus, cervix, and vagina. This tissue is subjected primarily to bi-axial forces in-vivo that significantly alter its structure and dimension over time, compromising its support function and leading to pelvic floor disorders. In this study, we present the first rigorous characterization of the collagen fiber microstructure and creep properties of the swine USL/CL complex by using scanning electron microscopy and planar biaxial testing in combination with three-dimensional digital image correlation. Collagen fiber bundles were found to be arranged into layers. Although the fiber bundles were oriented in multiple directions, 80.8% of them were aligned within +/-45[Formula: see text] to the main in-vivo loading direction. The straightness parameter, defined as the ratio of the end-to-end distance of a fiber bundle to its length, varied from 0.28 to 1.00, with 95.2% fiber bundles having a straightness parameter between 0.60 and 1.00. Under constant equi-biaxial loads of 2 and 4 N, the USL/CL complex exhibited significant creep both along the main in-vivo loading direction (the parallel direction) and along the direction perpendicular to it (the perpendicular direction). Specifically, over a 120-min period, the mean strain increased by 20-34[Formula: see text] in the parallel direction and 33-41[Formula: see text] in the perpendicular direction. However, there was no statistically significant difference in creep strains observed after 120 min between the parallel and perpendicular directions for either the 2 or 4 N load case. Creep proceeded slightly faster in the perpendicular direction under the equi-biaxial load of 2 N than under the equi-biaxial load of 4 N ([Formula: see text]). It proceeded significantly faster in the parallel direction under the equi-biaxial loads of 2 N than under the equi-biaxial loads of 4 N ([Formula: see text]). Overall, our findings contribute to a greater understanding of the biomaterial properties of the USL/CL complex that is needed for the development of new surgical reconstruction methods and mesh materials for pelvic floor disorders. PMID- 27256363 TI - Numerical simulation of blood flow in femoral perfusion: comparison between side armed femoral artery perfusion and direct femoral artery perfusion. AB - Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2 mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model. PMID- 27256365 TI - Comparing audiological test results obtained from a sound processor attached to a Softband with direct and magnetic passive bone conduction hearing implant systems. AB - The aim of this study was to compare audiological test results obtained from a sound processor (SP) attached to a Softband with those obtained from direct (abutment connection) bone conduction implant systems and magnetic passive bone conduction implant systems with different magnet strengths on patients implanted at our clinic. Twenty-four patients who were implanted with either an abutment or magnetic bone conduction implant system between January 2012 and December 2014 were analyzed for hearing results, such as free-field hearing thresholds, direct bone conduction hearing thresholds, and speech discrimination scores with aided and unaided conditions Both magnetic and direct osseointegrated bone conduction implant systems, as well as the Softband system, provide good hearing outcomes when compared with unaided performance; however, the abutment connection system gives better hearing thresholds in the higher frequencies. No significant difference in hearing gain was found between the Softband system, magnet 5, and magnet used by the patient. Magnetic and direct bone conduction hearing implant systems are both effective for rehabilitation of conductive and mixed hearing loss when conventional hearing aids cannot be used. However, patients with high frequency hearing loss may be better suited to an abutment connection system if they are not satisfied with high-frequency hearing gains provided via the trial Softband system preoperatively and should be counseled accordingly. PMID- 27256364 TI - Gene correction in patient-specific iPSCs for therapy development and disease modeling. AB - The discovery that mature cells can be reprogrammed to become pluripotent and the development of engineered endonucleases for enhancing genome editing are two of the most exciting and impactful technology advances in modern medicine and science. Human pluripotent stem cells have the potential to establish new model systems for studying human developmental biology and disease mechanisms. Gene correction in patient-specific iPSCs can also provide a novel source for autologous cell therapy. Although historically challenging, precise genome editing in human iPSCs is becoming more feasible with the development of new genome-editing tools, including ZFNs, TALENs, and CRISPR. iPSCs derived from patients of a variety of diseases have been edited to correct disease-associated mutations and to generate isogenic cell lines. After directed differentiation, many of the corrected iPSCs showed restored functionality and demonstrated their potential in cell replacement therapy. Genome-wide analyses of gene-corrected iPSCs have collectively demonstrated a high fidelity of the engineered endonucleases. Remaining challenges in clinical translation of these technologies include maintaining genome integrity of the iPSC clones and the differentiated cells. Given the rapid advances in genome-editing technologies, gene correction is no longer the bottleneck in developing iPSC-based gene and cell therapies; generating functional and transplantable cell types from iPSCs remains the biggest challenge needing to be addressed by the research field. PMID- 27256367 TI - Effects of age and period of fattening on carcass and non-carcass characteristics of one-humped camels. AB - This study was conducted to compare the carcass characteristics and quantity of carcass and non-carcass components of 2- and 3-year-old male camels fattened for either 3 or 6 months. Twelve 2-year-old camels with an average body live weight of 268.5 +/- 21.4 kg and twelve 3-year-old camels with an average body live weight of 307.5 +/- 29.9 kg were used in a completely randomized design with a 2 * 2 factorial arrangement. For carcass analysis, three camels from each group were selected and slaughtered. The results showed that camel age and fattening period had no significant effect on average daily gain (ADG). Older camels and a longer fattening period resulted in heavier hot and cold carcass weights. Three year-old camels had a higher dressing percentage compared to 2-year-old camels, regardless of the period of fattening. Analysis of non-carcass components showed that the heaviest component was the hide and 2-year-old camels fattened for 90 days had the greatest weight of hide as percentage of cold carcass weight. Total muscle weight was greater for the 3-year-old camels compared to the 2-year-old ones, regardless of the fattening period, and camels fattened for 180 days had heavier weight than those fattened for 90 days, regardless of age at fattening. However, the greatest weight of total muscle was detected in camels at 2 years of age fattened for 180 days when it was expressed as percentage of carcass weight. The highest and the lowest total fat content as kilogram or as percentage of cold carcass was observed in 3-year-old camels fattened for 180 days and 2-year-old camels fattened for 180 days, respectively. Our results suggested that the best age for slaughtering is 2 years old with the fattening period of 180 days. PMID- 27256366 TI - Thyroid cartilage invasion in laryngeal and hypopharyngeal squamous cell carcinoma treated with total laryngectomy. AB - The objective of this study is to analyze the accuracy of computed tomography in detecting malignant thyroid cartilage invasion. In a retrospective chart review, 120 patients with carcinoma of the larynx and hypopharynx underwent computed tomography before total laryngectomy. These data were compared with the histological specimens. Multidetector computed tomography (MDCT) scan had a positive predictive value (PPV) of 76 % and a negative predictive value (NPV) of 69 %. The specificity of MDCT was 89 % and sensitivity was 46 %. Comparison between radiologic suspected cartilage invasion and histologic results showed a significant correlation (p < 0.02). We found no significant impact of cartilage invasion concerning survival rates (5-year overall survival p = 0.683; 5-year disease-free survival p = 0.711). Preoperative CT scan is an important instrument in detecting neoplastic cartilage invasion. PMID- 27256368 TI - What would the NHS look like if the UK left the EU? PMID- 27256369 TI - Prostate Cancer Detection Rate with Koelis Fusion Biopsies versus Cognitive Biopsies: A Comparative Study. AB - OBJECTIVE: Targeted fusion biopsies have led to an improved prostate cancer (PCa) detection rate (CDR). Our aim was to assess if device-assisted fusion biopsies are superior to cognitive ones in terms of CDR. The association between multiparametric MRI parameters and PCa was also evaluated. METHODS: We retrospectively enrolled 50 patients who underwent transrectal biopsy with elastic fusion (Koelis; group KB, n = 25) or cognitive approach (group CB, n = 25). Targeted biopsies were done on targets, while a variable number of random biopsies were performed depending on the clinical case. RESULTS: The groups did not significantly differ in terms of age, prostate-specific antigen, prostate volume and previous biopsies. Mean number of random cores was significantly inferior in KB group (8.4 vs. 12.1) and mean number of targeted biopsies was significantly higher (3.6 vs. 2.6). CDR was higher in fusion biopsies (64 vs. 40%), with the gap becoming significant when considering CDR of MRI targets only (59 vs. 27%). The difference was marked for lesions <=10 mm, where CDR was 52% in KB against 21% in CB group. CONCLUSIONS: According to our study, elastic fusion biopsies performed with Koelis achieve an increased per-patient and per-lesion CDR as compared to cognitive biopsies, especially in the case of lesions <=10 mm. PMID- 27256371 TI - Risk-Taking, Delay Discounting, and Time Perspective in Adolescent Gamblers: An Experimental Study. AB - Previous research has demonstrated that adult pathological gamblers (compared to controls) show risk-proneness, foreshortened time horizon, and preference for immediate rewards. No study has ever examined the interplay of these factors in adolescent gambling. A total of 104 adolescents took part in the research. Two equal-number groups of adolescent non-problem and problem gamblers, defined using the South Oaks Gambling Screen-Revised for Adolescents, were administered the Balloon Analogue Risk Task (BART), the Consideration of Future Consequences (CFC 14) scale, and the Monetary Choice Questionnaire (MCQ). Adolescent problem gamblers were found to be more risk-prone, more oriented to the present, and to discount delay rewards more steeply than adolescent non-problem gamblers. Results of logistic regression analysis revealed that BART, MCQ, and CFC scores predicted gambling severity. These novel finding provides the first evidence of an association among problematic gambling, high risk-taking proneness, steep delay discounting, and foreshortened time horizon among adolescents. It may be that excessive gambling induces shortsighted behaviors that, in turn, facilitate gambling involvement. PMID- 27256370 TI - Dendritic cells in lung immunopathology. AB - Dendritic cells (DCs) lie at the heart of the innate immune system, specialised at recognising danger signals in many forms including foreign material, infection or tissue damage and initiating powerful adaptive immune and inflammatory responses. In barrier sites such as the lung, the instrumental role that DCs play at the interface between the environment and the host places them in a pivotal position in determining the severity of inflammatory disease. The past few years has seen a significant increase in our fundamental understanding of the subsets of DCs involved in pulmonary immunity, as well as the mechanisms by which they are activated and which they may use to coordinate downstream inflammation and pathology. In this review, we will summarise current understanding of the multi faceted role that DCs play in the induction, maintenance and regulation of lung immunopathology, with an emphasis on allergic pulmonary disease. PMID- 27256372 TI - Topiramate Combined with Cognitive Restructuring for the Treatment of Gambling Disorder: A Two-Center, Randomized, Double-Blind Clinical Trial. AB - Gambling disorder (GD) is a prevalent condition for which no pharmacological treatment has yet been approved, although there is evidence that topiramate can reduce impulsivity in GD and craving in various addictive behaviors. The goal of this study was to investigate the effectiveness of topiramate combined with cognitive restructuring for GD in a two-center, randomized, double-blind clinical trial. Participants were individuals seeking outpatient treatment for GD (n = 30), treated with either topiramate or placebo combined with a brief cognitive intervention, over a 12-week period, the dose of topiramate being tapered up during the first 8 weeks. The main outcome measures were gambling craving, behavior, and cognitive distortions; impulsivity; depression and social adjustment. Topiramate proved superior to placebo in reducing gambling craving (P = 0.017); time and money spent gambling (P = 0.007 and P = 0.047, respectively); cognitive distortions related to gambling (P = 0.003); and social adjustment (P = 0.040). We found no significant effects on impulsivity or depression. These findings are in contrast with data from a previous clinical trial with topiramate for GD. In the current study, we found that topiramate affects features specifically related to gambling addiction and had no significant effect on associated phenomena such as impulsiveness and depression. We believe that this response could be due to synergistic interaction between topiramate and the cognitive intervention. PMID- 27256373 TI - Impact of a Casino Opening on Gambling Behaviors of People Engaged in Methadone Maintenance. AB - This study examined gambling behavior in the context of a newly opening casino, comparing disordered gamblers to non-disordered gamblers, in a population of individuals involved in methadone maintenance treatment. Disordered gamblers (N = 50) and non-disordered gamblers (N = 50) were surveyed before and after the opening of a new casino on gambling behaviors, substance use, and psychological symptoms. No statistically significant changes in gambling behaviors were observed for disordered gamblers or non-disordered gamblers across time points; however, non-disordered gamblers demonstrated non-significant increases in horse and dog race betting, electronic games, and casino table games. As expected, disordered gamblers were found to spend significantly more money on electronic games and casino table games (p < 0.05) and demonstrated higher rates of drug use and impulsivity than non-disordered gamblers. The introduction of a new casino did not appear to have a major impact on gambling behaviors of individuals attending methadone maintenance treatment, though the non-significant increases in gambling among non-disordered gamblers may indicate that this population is preferentially impacted by the opening of a new casino. Future investigation into the longer term effects of opening a new casino on this population may be warranted. PMID- 27256374 TI - ERK1 as a Therapeutic Target for Dendritic Cell Vaccination against High-Grade Gliomas. AB - Glioma regression requires the recruitment of potent antitumor immune cells into the tumor microenvironment. Dendritic cells (DC) play a role in immune responses to these tumors. The fact that DC vaccines do not effectively combat high-grade gliomas, however, suggests that DCs need to be genetically modified specifically to promote their migration to tumor relevant sites. Previously, we identified extracellular signal-regulated kinase (ERK1) as a regulator of DC immunogenicity and brain autoimmunity. In the current study, we made use of modern magnetic resonance methods to study the role of ERK1 in regulating DC migration and tumor progression in a model of high-grade glioma. We found that ERK1-deficient mice are more resistant to the development of gliomas, and tumor growth in these mice is accompanied by a higher infiltration of leukocytes. ERK1-deficient DCs exhibit an increase in migration that is associated with sustained Cdc42 activation and increased expression of actin-associated cytoskeleton-organizing proteins. We also demonstrated that ERK1 deletion potentiates DC vaccination and provides a survival advantage in high-grade gliomas. Considering the therapeutic significance of these results, we propose ERK1-deleted DC vaccines as an additional means of eradicating resilient tumor cells and preventing tumor recurrence. Mol Cancer Ther; 15(8); 1975-87. (c)2016 AACR. PMID- 27256375 TI - In Silico Analysis Guides Selection of BET Inhibitors for Triple-Negative Breast Cancer Treatment. AB - Triple-negative breast cancer (TNBC) is an incurable disease with poor prognosis. At this moment, therapeutic options are limited to chemotherapy, and no targeted agent has reached the clinical setting. Bromodomain and extraterminal (BET) inhibitors are a new family of compounds that inhibit bromodomain-containing proteins affecting the expression of transcription factors, therefore modifying the expression of relevant oncogenic genes. In the present article, by using an in silico approach, we have identified the expression of upregulated transcription factors in TNBC compared with normal breast. Treatment with JQ1, a well-characterized BET inhibitor, modified some transcription factors, including DEP domain containing 1 (DEPDC), Forkhead box M1 (FOXM1), and Lim domain only 4 (LM04). In cell line models, administration of JQ1 or OTX015, another BET inhibitor, produced a significant antiproliferative effect and synergized with chemotherapies. Biochemical evaluation demonstrated an arrest at G1 as the main mechanism of action with a clear increase of p27. Addition of these compounds to chemotherapy induced apoptosis compared to each agent given alone. Evaluation of JQ1 in xenografted tumors in nude mice showed a profound antitumoral effect with a reduction of DEPDC, FOXM1, and LM04, in addition to an increase of p27. Globally, our data demonstrate the antitumor effect of this new family of compounds in TNBC, paving the way for its future clinical development. Mol Cancer Ther; 15(8); 1823-33. (c)2016 AACR. PMID- 27256377 TI - High Levels of Expression of P-glycoprotein/Multidrug Resistance Protein Result in Resistance to Vintafolide. AB - Targeting surface receptors overexpressed on cancer cells is one way to specifically treat cancer versus normal cells. Vintafolide (EC145), which consists of folate linked to a cytotoxic small molecule, desacetylvinblastine hydrazide (DAVLBH), takes advantage of the overexpression of folate receptor (FR) on cancer cells. Once bound to FR, vintafolide enters the cell by endocytosis, and the reducing environment of the endosome cleaves the linker, releasing DAVLBH to destabilize microtubules. Vintafolide has shown efficacy and improved tolerability compared with DAVLBH in FR-positive preclinical models. As the first FR-targeting drug to reach the clinic, vintafolide has achieved favorable responses in phase II clinical trials in FR-positive ovarian and lung cancer. However, some FR-positive patients in these clinical trials do not respond to vintafolide. We sought to identify potential biomarkers of resistance to aid in the future development of this and other FR-targeting drugs. Here, we confirm that high P-glycoprotein (P-gp) expression was the strongest predictor of resistance to DAVLBH in a panel of 359 cancer cell lines. Furthermore, targeted delivery of DAVLBH via the FR, as in vintafolide, fails to overcome P-gp-mediated efflux of DAVLBH in both in vitro and in vivo preclinical models. Therefore, we suggest that patients whose tumors express high levels of P-gp be excluded from future clinical trials for vintafolide as well as other FR-targeted therapeutics bearing a P-gp substrate. Mol Cancer Ther; 15(8); 1998-2008. (c)2016 AACR. PMID- 27256376 TI - SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody-Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression. AB - Uterine serous carcinoma (USC) is an aggressive form of endometrial cancer. Up to 35% of USC may overexpress the HER2/neu oncogene at strong (i.e., 3+) levels by IHC while an additional 40% to 50% express HER2/neu at moderate (2+) or low (1+) levels. We investigated the efficacy of SYD985, (Synthon Biopharmaceuticals), a novel HER2-targeting antibody-drug conjugate (ADC) composed of the mAb trastuzumab linked to a highly potent DNA-alkylating agent (i.e., duocarmycin) in USC. We also compared the antitumor activity of SYD985 in head-to-head experiments to trastuzumab emtansine (T-DM1), a FDA-approved ADC, against multiple primary USC cell lines expressing different levels of HER2/neu in in vitro and in vivo experiments. Using antibody-dependent cellular cytotoxicity (ADCC), proliferation, viability, and bystander killing assays as well as propidium iodide-based flow cytometry assays and multiple in vivo USC mouse xenograft models, we demonstrate for the first time that SYD985 is a novel ADC with activity against USC with strong (3+) as well as low to moderate (i.e., 1+/2+) HER2/neu expression. SYD985 is 10- to 70-fold more potent than T-DM1 in comparative experiments and, unlike T-DM1, it is active against USC demonstrating moderate/low or heterogeneous HER2/neu expression. Clinical studies with SYD985 in patients harboring chemotherapy-resistant USC with low, moderate, and high HER2 expression are warranted. Mol Cancer Ther; 15(8); 1900-9. (c)2016 AACR. PMID- 27256379 TI - Proceedings of the RAMI Intern Section Meeting, 30 January 2016, Royal College of Physicians of Ireland. PMID- 27256378 TI - Bruton's Tyrosine Kinase Inhibitors Prevent Therapeutic Escape in Breast Cancer Cells. AB - We have reported that a novel isoform of BTK (BTK-C) expressed in breast cancer protects these cells from apoptosis. In this study, we show that recently developed inhibitors of BTK, such as ibrutinib (PCI-32765), AVL-292, and CGI 1746, reduce breast cancer cell survival and prevent drug-resistant clones from arising. Ibrutinib treatment impacts HER2(+) breast cancer cell viability at lower concentrations than the established breast cancer therapeutic lapatinib. In addition to inhibiting BTK, ibrutinib, but not AVL-292 and CGI-1746, efficiently blocks the activation of EGFR, HER2, ErbB3, and ErbB4. Consequently, the activation of AKT and ERK signaling pathways are also blocked leading to a G1-S cell-cycle delay and increased apoptosis. Importantly, inhibition of BTK prevents activation of the AKT signaling pathway by NRG or EGF that has been shown to promote growth factor-driven lapatinib resistance in HER2(+) breast cancer cells. HER2(+) breast cancer cell proliferation is blocked by ibrutinib even in the presence of these factors. AVL-292, which has no effect on EGFR family activation, prevents NRG- and EGF-dependent growth factor-driven resistance to lapatinib in HER2(+) breast cancer cells. In vivo, ibrutinib inhibits HER2(+) xenograft tumor growth. Consistent with this, immunofluorescence analysis of xenograft tumors shows that ibrutinib reduces the phosphorylation of HER2, BTK, Akt, and Erk and histone H3 and increases cleaved caspase-3 signals. As BTK-C and HER2 are often coexpressed in human breast cancers, these observations indicate that BTK-C is a potential therapeutic target and that ibrutinib could be an effective drug especially for HER2(+) breast cancer. Mol Cancer Ther; 15(9); 2198 208. (c)2016 AACR. PMID- 27256380 TI - Experimental and Computational Considerations in the Study of RNA-Binding Protein RNA Interactions. AB - After an RNA is transcribed, it undergoes a variety of processing steps that can change the encoded protein sequence (through alternative splicing and RNA editing), regulate the stability of the RNA, and control subcellular localization, timing, and rate of translation. The recent explosion in genomics techniques has enabled transcriptome-wide profiling of RNA processing in an unbiased manner. However, it has also brought with it both experimental challenges in developing improved methods to probe distinct processing steps, as well as computational challenges in data storage, processing, and analysis tools to enable large-scale interpretation in the genomics era. In this chapter we review experimental techniques and challenges in profiling various aspects of RNA processing, as well as recent efforts to develop analyses integrating multiple data sources and techniques to infer RNA regulatory networks. PMID- 27256381 TI - Genome-Wide Approaches for RNA Structure Probing. AB - RNA molecules of all types fold into complex secondary and tertiary structures that are important for their function and regulation. Structural and catalytic RNAs such as ribosomal RNA (rRNA) and transfer RNA (tRNA) are central players in protein synthesis, and only function through their proper folding into intricate three-dimensional structures. Studies of messenger RNA (mRNA) regulation have also revealed that structural elements embedded within these RNA species are important for the proper regulation of their total level in the transcriptome. More recently, the discovery of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) has shed light on the importance of RNA structure to genome, transcriptome, and proteome regulation. Due to the relatively small number, high conservation, and importance of structural and catalytic RNAs to all life, much early work in RNA structure analysis mapped out a detailed view of these molecules. Computational and physical methods were used in concert with enzymatic and chemical structure probing to create high-resolution models of these fundamental biological molecules. However, the recent expansion in our knowledge of the importance of RNA structure to coding and regulatory RNAs has left the field in need of faster and scalable methods for high-throughput structural analysis. To address this, nuclease and chemical RNA structure probing methodologies have been adapted for genome-wide analysis. These methods have been deployed to globally characterize thousands of RNA structures in a single experiment. Here, we review these experimental methodologies for high-throughput RNA structure determination and discuss the insights gained from each approach. PMID- 27256383 TI - Single Molecule Approaches in RNA-Protein Interactions. AB - RNA-protein interactions govern every aspect of RNA metabolism, and aberrant RNA binding proteins are the cause of hundreds of genetic diseases. Quantitative measurements of these interactions are necessary in order to understand mechanisms leading to diseases and to develop efficient therapies. Existing methods of RNA-protein interactome capture can afford a comprehensive snapshot of RNA-protein interaction networks but lack the ability to characterize the dynamics of these interactions. As all ensemble methods, their resolution is also limited by statistical averaging. Here we discuss recent advances in single molecule techniques that have the potential to tackle these challenges. We also provide a thorough overview of single molecule colocalization microscopy and the essential protein and RNA tagging and detection techniques. PMID- 27256384 TI - RNA Dynamics in the Control of Circadian Rhythm. AB - The circadian oscillator is based on transcription-translation feedback loops that generate 24 h oscillations in gene expression. Although circadian regulation of mRNA expression at the transcriptional level is one of the most important steps for the generation of circadian rhythms within the cell, multiple lines of evidence point to a disconnect between transcript oscillation and protein oscillation. This can be explained by regulatory RNA-binding proteins acting on the nascent transcripts to modulate their processing, export, translation and degradation rates. In this chapter we will review what is known about the different steps involved in circadian gene expression from transcription initiation to mRNA stability and translation efficiency. The role of ribonucleoprotein particles in the generation of rhythmic gene expression is only starting to be elucidated, but it is likely that they cooperate with the basal transcriptional machinery to help to maintain the precision of the clock under diverse cellular and environmental conditions. PMID- 27256382 TI - Tethered Function Assays as Tools to Elucidate the Molecular Roles of RNA-Binding Proteins. AB - Dynamic regulation of RNA molecules is critical to the survival and development of cells. Messenger RNAs are transcribed in the nucleus as intron-containing pre mRNAs and bound by RNA-binding proteins, which control their fate by regulating RNA stability, splicing, polyadenylation, translation, and cellular localization. Most RBPs have distinct mRNA-binding and functional domains; thus, the function of an RBP can be studied independently of RNA-binding by artificially recruiting the RBP to a reporter RNA and then measuring the effect of RBP recruitment on reporter splicing, stability, translational efficiency, or intracellular trafficking. These tethered function assays therefore do not require prior knowledge of the RBP's endogenous RNA targets or its binding sites within these RNAs. Here, we provide an overview of the experimental strategy and the strengths and limitations of common tethering systems. We illustrate specific examples of the application of the assay in elucidating the function of various classes of RBPs. We also discuss how classic tethering assay approaches and insights gained from them have been empowered by more recent technological advances, including efficient genome editing and high-throughput RNA-sequencing. PMID- 27256386 TI - Regulation of Stem Cell Self-Renewal and Oncogenesis by RNA-Binding Proteins. AB - Throughout their life span, multicellular organisms rely on stem cell systems. During development pluripotent embryonic stem cells give rise to all cell types that make up the organism. After birth, tissue stem cells maintain properly functioning tissues and organs under homeostasis as well as promote regeneration after tissue damage or injury. Stem cells are capable of self-renewal, which is the ability to divide indefinitely while retaining the potential of differentiation into multiple cell types. The ability to self-renew, however, is a double-edged sword; the molecular mechanisms of self-renewal can be a target of malignant transformation driving tumor development and progression. Growing lines of evidence have shown that RNA-binding proteins (RBPs) play pivotal roles in the regulation of self-renewal by modulating metabolism of coding and non-coding RNAs both in normal tissues and in cancers. In this review, we discuss our current understanding of tissue stem cell systems and how RBPs regulate stem cell fates as well as how the regulatory functions of RBPs contribute to oncogenesis. PMID- 27256387 TI - Controlling the Editor: The Many Roles of RNA-Binding Proteins in Regulating A-to I RNA Editing. AB - RNA editing is a cellular process used to expand and diversify the RNA transcripts produced from a generally immutable genome. In animals, the most prevalent type of RNA editing is adenosine (A) to inosine (I) deamination catalyzed by the ADAR family. Throughout development, A-to-I editing levels increase while ADAR expression is constant, suggesting cellular mechanisms to regulate A-to-I editing exist. Furthermore, in several disease states, ADAR expression levels are similar to the normal state, but A-to-I editing levels are altered. Therefore, understanding how these enzymes are regulated in normal tissues and misregulated in disease states is of profound importance. This chapter will both discuss how to identify A-to-I editing sites across the transcriptome and explore the mechanisms that regulate ADAR editing activity, with particular focus on the diverse types of RNA-binding proteins implicated in regulating A-to-I editing in vivo. PMID- 27256388 TI - Splicing Factor Mutations in Cancer. AB - Many cancers demonstrate aberrant splicing patterns that contribute to their development and progression. Recently, recurrent somatic mutations of genes encoding core subunits of the spliceosome have been identified in several different cancer types. These mutations are most common in hematologic malignancies like the myelodysplastic syndromes (MDS), acute myeloid leukemia, and chronic lymphocytic leukemia, but also in occur in several solid tumors at lower frequency. The most frequent mutations occur in SF3B1, U2AF1, SRSF2, and ZRSR2 and are largely exclusive of each other. Mutations in SF3B1, U2AF1, and SRSF2 acquire heterozygous missense mutations in specific codons, resembling oncogenes. ZRSR2 mutations include clear loss-of-function variants, a pattern more common to tumor suppressor genes. These splicing factors are associated with distinct clinical phenotypes and patterns of mutation in different malignancies. Mutations have both diagnostic and prognostic relevance. Splicing factor mutations appear to affect only a minority of transcripts which show little overlap by mutation type. How differences in splicing caused by somatic mutations of spliceosome subunits lead to oncogenesis is not clear and may involve different targets in each disease type. However, cells with mutated splicing machinery may be particularly vulnerable to further disruption of the spliceosome suggesting a novel strategy for the targeted therapy of cancers. PMID- 27256385 TI - Roles of RNA-binding Proteins and Post-transcriptional Regulation in Driving Male Germ Cell Development in the Mouse. AB - Tissue development and homeostasis are dependent on highly regulated gene expression programs in which cell-specific combinations of regulatory factors determine which genes are expressed and the post-transcriptional fate of the resulting RNA transcripts. Post-transcriptional regulation of gene expression by RNA-binding proteins has critical roles in tissue development-allowing individual genes to generate multiple RNA and protein products, and the timing, location, and abundance of protein synthesis to be finely controlled. Extensive post transcriptional regulation occurs during mammalian gametogenesis, including high levels of alternative mRNA expression, stage-specific expression of mRNA variants, broad translational repression, and stage-specific activation of mRNA translation. In this chapter, an overview of the roles of RNA-binding proteins and the importance of post-transcriptional regulation in male germ cell development in the mouse is presented. PMID- 27256389 TI - Regulation of Tissue-Specific Alternative Splicing: C. elegans as a Model System. AB - Alternative pre-mRNA splicing serves as an elegant mechanism for generating transcriptomic and proteomic diversity between cell and tissue types. In this chapter, we highlight key concepts and outstanding goals in studies of tissue and cell-specific alternative splicing. We place particular emphasis on the use of C. elegans as a tractable model organism for in vivo studies of alternative splicing between tissues and also at single cell resolution. We describe our current understanding of tissue and cell-specific regulation in the animal, and emerging techniques that will allow for future mechanistic studies as well as systems level investigations of spatio-temporal splicing under laboratory conditions and in response to environmental stimuli. PMID- 27256391 TI - Post-Translational Modifications and RNA-Binding Proteins. AB - RNA-binding proteins affect cellular metabolic programs through development and in response to cellular stimuli. Though much work has been done to elucidate the roles of a handful of RNA-binding proteins and their effect on RNA metabolism, the progress of studies to understand the effects of post-translational modifications of this class of proteins is far from complete. This chapter summarizes the work that has been done to identify the consequence of post translational modifications to some RNA-binding proteins. The effects of these modifications have been shown to increase the panoply of functions that a given RNA-binding protein can assume. We will survey the experimental methods that are used to identify the presence of several protein modifications and methods that attempt to discern the consequence of these modifications. PMID- 27256392 TI - Land-use and land-cover change in Western Ghats of India. AB - The Western Ghats (WG) of India, one of the hottest biodiversity hotspots in the world, has witnessed major land-use and land-cover (LULC) change in recent times. The present research was aimed at studying the patterns of LULC change in WG during 1985-1995-2005, understanding the major drivers that caused such change, and projecting the future (2025) spatial distribution of forest using coupled logistic regression and Markov model. The International Geosphere Biosphere Program (IGBP) classification scheme was mainly followed in LULC characterization and change analysis. The single-step Markov model was used to project the forest demand. The spatial allocation of such forest demand was based on the predicted probabilities derived through logistic regression model. The R statistical package was used to set the allocation rules. The projection model was selected based on Akaike information criterion (AIC) and area under receiver operating characteristic (ROC) curve. The actual and projected areas of forest in 2005 were compared before making projection for 2025. It was observed that forest degradation has reduced from 1985-1995 to 1995-2005. The study obtained important insights about the drivers and their impacts on LULC simulations. To the best of our knowledge, this is the first attempt where projection of future state of forest in entire WG is made based on decadal LULC and socio-economic datasets at the Taluka (sub-district) level. PMID- 27256390 TI - RNA Granules and Diseases: A Case Study of Stress Granules in ALS and FTLD. AB - RNA granules are microscopically visible cellular structures that aggregate by protein-protein and protein-RNA interactions. Using stress granules as an example, we discuss the principles of RNA granule formation, which rely on the multivalency of RNA and multi-domain proteins as well as low-affinity interactions between proteins with prion-like/low-complexity domains (e.g. FUS and TDP-43). We then explore how dysregulation of RNA granule formation is linked to neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), and discuss possible strategies for therapeutic intervention. PMID- 27256393 TI - Infiltrating immune cells and gene mutations in pancreatic ductal adenocarcinoma. AB - BACKGROUND: The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral infiltrating immune/inflammatory cells (IICs) in patients after surgery. METHODS: Eighteen phenotypic markers representing 11 types of IIC and the protein products of genes TP53, CDKN2A/p16 and SMAD4/DPC4 were assessed by immunohistochemistry of specimens from patients with pancreatic cancer. The expression of IICs and the mutational status of the genes were correlated with tumour recurrence and survival, and results were validated in an independent cohort. RESULTS: CD15+ neutrophils, CD20+ B cells and CD206+ tumour-associated macrophages were seen frequently in tumours, and their presence was associated with reduced survival in a cohort of 79 patients. Expression of CD4+ T helper cells, CD8+ cytotoxic T lymphocytes and CD117+ mast cells was associated with a favourable prognosis. A weighted Cox regression recurrence-predictive model was constructed that showed good correlation of IICs and gene mutations. A combination of CD15, CD206, CD117 and Smad4 expression was independently associated with overall (hazard ratio (HR) 3.63, 95 per cent c.i. 2.18 to 6.04; P < 0.001) and recurrence-free (HR 2.93, 1.81 to 4.75; P < 0.001) survival. These findings were validated in an independent cohort (151 patients) and in 54 tissue samples obtained by preoperative endoscopic ultrasound-guided fine-needle aspiration. CONCLUSION: PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy. Surgical relevance The immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4. This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC. PMID- 27256394 TI - Duration of Viral Suppression and Risk of Rebound Viremia with First-Line Antiretroviral Therapy in Rural Uganda. AB - Little is known about associations between viral suppression, adherence, and duration of prior viral suppression in sub-Saharan Africa. Study participants were from the UARTO study in Mbarara, Uganda. We fit regression models to characterize relationships between average adherence, treatment interruptions, and rebound viremia (>400 copies/mL) following a previously undetectable result. Our goal was to understand the impact of prior viral suppression on these relationships. 396 participants contributed 2864 quarterly visits. Restricted to periods with average adherence <50 %, each 10 % increase in adherence reduced the odds of rebound viremia by 74 % [adjusted odds ratio (AOR) = 0.26, P = 0.002] and 29 % (AOR = 0.71, P = 0.057) during the first 12 months of suppression and beyond 12 months respectively, interaction term P = 0.018. Among periods with adherence >=50 %, the risk of rebound viremia decreased with increasing adherence during the first 12 months of viral suppression (AOR = 0.73 for each 10 % increase, P = 0.001), but not thereafter (AOR = 1.09, P = 0.67), interaction term P = 0.027. In contrast, 72-h interruptions, were associated with increased rebound viremia during the first 12 months (AOR = 1.30, P = 0.009) and after (AOR = 1.39, P = 0.005), interaction term P = 0.69. Completing 12 months of viral suppression decreases the impact of average adherence, but not prolonged treatment interruptions, on risk of rebound viremia. PMID- 27256395 TI - Remodeling of bovine oviductal epithelium by mitosis of secretory cells. AB - Two types of oviductal epithelial cells, secretory and ciliated, play crucial roles in the first days after fertilization in mammals. Secretory cells produce various molecules promoting embryo development, while ciliated cells facilitate transport of oocytes and zygotes by ciliary beating. The proportions of the two cell types change during the estrous cycle. The proportion of ciliated cells on the oviductal luminal surface is abundant at the follicular phase, whereas the proportion of secretory cells gradually increases with the formation of the corpus luteum. In the present study, we hypothesize that the proportions of ciliated and secretory epithelial cells are regulated by mitosis. The proportion of the cells being positive for FOXJ1 (a ciliated cell marker) or Ki67 (a mitosis marker) in epithelial cells during the estrous cycle were immunohistochemically examined. Ki67 and FOXJ1 or PAX8 (a secretory cell marker), were double-stained to clarify which types of epithelial cells undergo mitosis. In the ampulla, the percentage of FOXJ1-positive cells was highest at the day of ovulation (Day 0) and decreased by about 50 % by Days 8-12, while in the isthmus it did not change during the estrous cycle. The proportion of Ki67-positive cells was highest at around the time of ovulation in both the ampulla and isthmus. All the Ki67 positive cells were PAX8-positive and FOXJ1-negative in both the ampulla and isthmus. These findings suggest that epithelial remodeling, which is regulated by differentiation and/or proliferation of secretory cells of the oviduct, provides the optimal environment for gamete transport, fertilization and embryonic development. PMID- 27256396 TI - Scarless wound healing: finding the right cells and signals. AB - From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/beta-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal adhesion kinase). PMID- 27256397 TI - MiR-1908 promotes scar formation post-burn wound healing by suppressing Ski mediated inflammation and fibroblast proliferation. AB - The cell biological basis for scar formation is mainly via excessive fibroblast proliferation accompanied by hypernomic Col I accumulation and inflammation. The role of miR-1908 in scar formation has not been investigated. In this study, we found that miR-1908 expression was inversely associated with the scar suppressor Ski in normal, burn-wounded, healing and scar dermal tissues in humans. Bioinformatics and luciferase reporter gene assays confirmed that miR-1908 targeted the 3'UTR region of Ski mRNA and suppressed Ski expression. Next, human scar epidermal fibroblasts were isolated and the miR-1908 oligonucleotide mimic and inhibitor were respectively transfected into the cells. Western blot analysis proved that Ski expression was sharply reduced by the miR-1908 mimic. MTT and Cell Counting Kit-8 analyses showed that miR-1908 mimic transfection promoted cell proliferation. Simultaneously, data on real-time qPCR analysis indicated that expression of the fibrotic master gene TGF-beta1, Ski-suppressing gene Meox2, Col I and proinflammatory markers IL-1alpha and TNF-alpha, were all significantly upregulated. In contrast, the miR-1908 inhibitor had a completely opposite effect on cell proliferation and gene expression. The mimic and inhibitor were locally injected into rats with abdominal burn-wounded scars during a 180-day, post-healing experiment. The miR-1908 mimic injection significantly reduced Ski expression, as well as the area, volume and fibrosis of scars in vivo. And, in contrast, the miR-1908 inhibitor injection had an opposite effect to that of the miR-1908 mimic injection. In conclusion, miR-1908 had a positive role in scar formation by suppressing Ski-mediated inflammation and fibroblast proliferation in vitro and in vivo. PMID- 27256398 TI - Anandamide transporter-mediated regulation of the micturition reflex in urethane anesthetized rats. AB - PURPOSE: The aim of this study was to investigate the effects of an anandamide transporter inhibitor that can increase endogenous anandamide concentration on the micturition reflex in urethane-anesthetized rats. METHODS: Continuous cystometrograms were performed in female Sprague-Dawley rats under urethane anesthesia. After stable micturition cycles were established, VDM11 (1, 3 and 10 mg/kg), an anandamide membrane transporter inhibitor, was administered intravenously to evaluate changes in bladder activity. In experiments examining the effects of cannabinoid (CB) receptor antagonists, VDM11 (10 mg/kg) was injected intravenously when the first bladder contraction was observed after intravenous administration of AM251, a CB1 receptor antagonist (3 mg/kg), or AM630, a CB2 receptor antagonist (3 mg/kg). RESULTS: Intravenous administration of VDM11 increased intercontraction intervals and threshold pressure at doses of 3 mg/kg or higher in dose-dependent fashion. When AM251 was administered one voiding cycle before VDM11 administration, the increases in intercontraction intervals and threshold pressure induced by VDM11 administration alone were not seen. In contrast, when AM630 was administered before VDM11 administration, increases in intercontraction intervals and threshold pressure were observed, as they were after VDM11 alone. CONCLUSION: These results suggest that anandamide, an endogenous CB ligand, can modulate the micturition reflex and that anandamide transporters play an important role in this modulation. In urethane-anesthetized rats, inhibition of the uptake of anandamide can inhibit the micturition reflex and these inhibitory effects of VDM11 are at least in part mediated by the CB1 receptor. PMID- 27256399 TI - Cardiovascular risk after androgen deprivation therapy for prostate cancer: an Asian perspective. AB - Androgen deprivation therapy (ADT) plays an important role in managing prostate cancer. However, ADT may result in major cardiovascular events and potentially lead to fatal consequences. Cardiovascular disease is the leading cause of mortality and it is a very important health condition to look into. Asians and Caucasians differ both physiologically and genetically, and they may have display different cardiovascular profiles. In this article, we reviewed the literature focusing on the cardiovascular risk after ADT for prostate cancer in the Asian population. We would discuss about the pathogenesis of ADT leading to cardiovascular events, summarize the findings concerning cardiac and stroke risks after ADT, compare between the different modalities of ADT and also provide genetic basics which are unique to Asians. We hope this article would provide more insights into the cardiovascular risk after ADT for prostate cancer in an Asian perspective. PMID- 27256400 TI - 14-3-3 eta isoform colocalizes TDP-43 on the coarse granules in the anterior horn cells of patients with sporadic amyotrophic lateral sclerosis. AB - The immunolocalization of the 14-3-3 eta isoform in the anterior horn cells (AHCs) of patients with sporadic amyotrophic lateral sclerosis (ALS) and controls was examined. Compared with the immunolocalization of other 14-3-3 isoforms, the immunolocalization of the 14-3-3 eta isoform was either synaptic at the periphery of AHCs, spindle-shaped in neurites, or granular in the cytoplasm. By double labeling with phosphorylated (p-)TDP-43, the transactivation response DNA binding protein of 43kDa (TDP-43) demonstrated frequent colocalization of the 14-3-3 eta isoform in granular structures (90%) and spindle-shaped structures (85.4%), but not in p-TDP-43-positive round inclusions. It is speculated that the 14-3-3 eta isoform is associated with not only a synaptic pathology of ALS but also TDP positive small lesions in the cytoplasm and neurites. The absence of eta-like immunoreactivity in p-TDP-43-positive large inclusions suggests the restricted relevance of the 14-3-3 eta isoform during ALS pathogenesis to some phases of the p-TDP pathology. PMID- 27256401 TI - Repetitive transcranial magnetic stimulation regulates L-type Ca(2+) channel activity inhibited by early sevoflurane exposure. AB - BACKGROUND: Sevoflurane might be harmful to the developing brain. Therefore, it is essential to reverse sevoflurane-induced brain injury. OBJECTIVE: This study aimed to determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) can regulate L-type Ca(2+) channel activity, which is inhibited by early sevoflurane exposure. METHODS: Rats were randomly divided into three groups: control, sevoflurane, and rTMS groups. A Whole-cell patch clamp technique was applied to record L-type Ca(2+) channel currents. The I-V curve, steady-state activation and inactivation curves were studied in rats of each group at different ages (1 week, 2 weeks, 3 weeks, 4 weeks and 5 weeks old). RESULTS: In the control group, L-type Ca(2+) channel current density significantly increased from week 2 to week 3. Compared with the control group, L type Ca(2+) channel currents of rats in the sevoflurane group were significantly inhibited from week 1 to week 3. Activation curves of L-type Ca(2+) channel shifted significantly towards depolarization at week 1 and week 2. Moreover, steady-state inactivation curves shifted towards hyperpolarization from week 1 to week 3. Compared with the sevoflurane group, rTMS significantly increased L-type Ca(2+) channel currents at week 2 and week 3. Activation curves of L-type Ca(2+) channel significantly shifted towards hyperpolarization at week 2. Meanwhile, steady-state inactivation curves significantly shifted towards depolarization at week 2. CONCLUSIONS: The period between week 2 and week 3 is critical for the development of L-type Ca(2+) channels. Early sevoflurane exposure inhibits L-type Ca(2+) channel activity and rTMS can regulate L-type Ca(2+) channel activity inhibited by sevoflurane. PMID- 27256402 TI - The Pathologic Point of View of Laparoscopic Adrenalectomy in the Era of Radiologic Imaging: A Multicenter Retrospective Study. AB - INTRODUCTION/AIM: This study aimed to determine if laparoscopic adrenalectomy (LA) is feasible for the treatment of adrenal malignancies and metastasis, and to review the final pathology findings in order to clarify the indications for surgery. MATERIALS AND METHOD: The medical records of all patients that underwent LA at 3 university hospitals between January 1, 2008, and May 1, 2015, were retrospectively reviewed. RESULTS: In total, 189 laparoscopic adrenalectomies were completed successfully. Mean duration of surgery was 79.3 +/- 38.6 min and mean estimated intraoperative blood loss was 39.9 ml. Intraoperatively, 4 patients had major complications: spleen injury (n = 1), renal vein injury (n = 2) and diaphragm injury (n = 2). Histopathological examination showed that there were 20 different types of lesions. Surgical margins (SMs) were tumor free in 95.2% of the patients. Moreover, SMs were tumor free in all patients with adrenocortical carcinomas; however, positive margins were noted in 7 of 23 patients (30.4%) with malignant adrenal tumors. CONCLUSIONS: The present findings support the use of laparoscopy for metastatic adrenal masses, despite a high positive margin rate. LA is a safe, feasible and cost-effective procedure for the management of benign and malignant adrenal masses. PMID- 27256403 TI - Reduced-portion entrees in a worksite and restaurant setting: impact on food consumption and waste. AB - OBJECTIVE: Large portion sizes in restaurants have been identified as a public health risk. The purpose of the present study was to determine whether customers in two different food-service operator segments (non-commercial worksite cafeteria and commercial upscale restaurant) would select reduced-portion menu items and the impact of selecting reduced-portion menu items on energy and nutrient intakes and plate waste. DESIGN: Consumption and plate waste data were collected for 5 weeks before and 7 weeks after introduction of five reduced-size entrees in a worksite lunch cafeteria and for 3 weeks before and 4 weeks after introduction of five reduced-size dinner entrees in a restaurant setting. Full size entrees were available throughout the entire study periods. SETTING: A worksite cafeteria and a commercial upscale restaurant in a large US Midwestern metropolitan area. SUBJECTS: Adult worksite employees and restaurant patrons. RESULTS: Reduced-size entrees accounted for 5.3-12.8 % and 18.8-31.3 % of total entrees selected in the worksite and restaurant settings, respectively. Food waste, energy intake and intakes of total fat, saturated fat, cholesterol, Na, fibre, Ca, K and Fe were significantly lower when both full- and reduced-size entrees were served in the worksite setting and in the restaurant setting compared with when only full-size entrees were served. CONCLUSIONS: A relatively small proportion of reduced-size entrees were selected but still resulted in reductions in overall energy and nutrient intakes. These outcomes could serve as the foundation for future studies to determine strategies to enhance acceptance of reduced-portion menu items in restaurant settings. PMID- 27256404 TI - Effect of (18)F-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses. AB - OBJECTIVE: The present study aimed to investigate the effect of (18)F fluorodeoxyglucose (FDG) extravasation on the time taken for tumoral uptake to reach a plateau. METHODS: For the animal experiment, FDG extravasation was conducted in the tails of HCT116 tumor-bearing xenograft mice models in three groups (no extravasation, 40 % extravasation, and 80 % extravasation; n = 5, each). Dynamic positron emission tomography (PET) images were acquired over a period of 2 h following injection. Time-activity curves for FDG in the tails and tumors were calculated. For the clinical experiment, 22 patients (male:female, 14:8; age range, 70.8 +/- 9.2 years) were subjected to PET/computed tomography (PET/CT) 1 h after the injection of FDG. The inclusion criteria were as follows: (1) submitted to both whole-body and subsequent regional scanning; (2) entire extravasation activity visualized in the whole-body images; (3) tumor visualized on both whole-body and additional regional images; and (4) status of tumor either confirmed by biopsy or clinically suspected for malignancy. The standardized uptake values (SUVs) of the tumors (on the whole-body and additional PET images) and extravasation sites were recorded. RESULTS: There were no significant differences in the time taken for tumoral uptake to reach a plateau and that to reach minimum activity at the extravasation site among the three groups of mice. However, the mean tumoral activity and activity at the extravasation site were negatively correlated at 1 h post-injection. According to the clinical PET findings, the differences in SUV between the whole-body and regional images were not significantly correlated with the interval between injection of FDG and start of whole-body scanning, interval between the start of whole-body scanning and start of regional scanning, extravasation volume, maximum SUV of the extravasation site, or total activity at the extravasation site. CONCLUSIONS: The time taken for tumoral uptake to reach a plateau is not affected by extravasation, even at extensive degrees. Thus, in routine practice, the imaging time of approximately 60 min post-injection need not be modified even if extravasation is identified. However, tumor SUV may be underestimated in cases of extravasation. PMID- 27256405 TI - Increased (18)F-fluorodeoxyglucose accumulation in bilateral adrenal glands of the patients suffering from vasovagal reaction due to blood vessel puncture. AB - OBJECTIVE: The purpose of the study was to evaluate the hypothesis that patients having a vasovagal reaction (VVR) after blood vessel puncture show increased FDG accumulation in bilateral adrenal glands. METHODS: Over the past 8 years, 26 patients experienced a VVR after blood vessel puncture following intra-venous injection of FDG at our institution. Of the 26 patients, 16 underwent multiple occasion FDG-PET/CT scans while suffering a VVR at only one examination. All 16 patients had no morphological abnormality in the adrenal glands on FDG-PET/CT and follow-up examination. For the 16, we retrospectively reviewed the FDG-PET/CT scan with respect to the adrenal glands and compared the result to that for the FDG-PET/CT scan of the same patient when there was no VVR event. We used both visual analysis and semi-quantitative analysis employing either maximum standardized uptake value (SUVmax) or adrenal-to-liver (A/L) SUVmax ratio. RESULTS: On visual analysis of the FDG-PET/CT with VVR, accumulations in both of the adrenal glands was judged positive, defined as higher than the hepatic accumulation, in 84 % of the cases. The SUVmax in the right adrenal gland was 2.79 +/- 0.69 with VVR and 1.92 +/- 0.33 without VVR; this value in the left adrenal gland was 3.07 +/- 0.71 with VVR and 2.05 +/- 0.39 without. Mean SUVmax of both adrenal glands was 2.93 +/- 0.66 with VVR and 1.98 +/- 0.35 without. The A/L SUVmax ratio in the right adrenal gland was 1.02 +/- 0.26 with VVR and 0.69 +/- 0.11 without; this value in the left was 1.11 +/- 0.23 with VVR and 0.74 +/- 0.15 without. The mean A/L SUVmax ratio of both adrenal glands was 1.06 +/- 0.24 with VVR and 0.72 +/- 0.13 without. Each parameter with VVR was significantly higher than that without. For the two adrenal glands, the mean SUVmax with VVR was 48 % higher than that without VVR. CONCLUSIONS: We confirmed the hypothesis that patients having a VVR after blood vessel puncture show increased FDG accumulation in their bilateral adrenal glands. This may reflect hyper-metabolism of the adrenal glands in synthesizing and secreting catecholamine. PMID- 27256406 TI - An antibody toolkit for the study of membrane traffic in Drosophila melanogaster. AB - The use of Drosophila melanogaster as a model organism has been pivotal to understanding the developmental processes of metazoans. However, the use of flies for studying subcellular organization is hampered by a paucity of reliable reagents to label specific organelles. Here, we describe the generation of mouse monoclonal antibodies against a set of markers of the secretory and endocytic pathways, along with goat polyclonal antibodies against two Golgi proteins. We show that the monoclonal antibodies are highly specific and sufficiently sensitive to detect endogenous proteins in crude extracts by immunoblotting with little background staining. By immunofluorescence the major compartments of the membrane traffic system (including the endoplasmic reticulum, the Golgi, and early and late endosomes) are labeled by at least one antibody. Moreover, the antibodies can be used to label organelles in fly tissues including salivary glands and wing imaginal discs. We anticipate that these antibodies will provide a useful tool kit to facilitate the investigation of how the endomembrane system functions and varies in the diverse tissue types of metazoans. PMID- 27256407 TI - Combined cisplatin and aurora inhibitor treatment increase neuroblastoma cell death but surviving cells overproduce BDNF. AB - Drug-resistance to chemotherapics in aggressive neuroblastoma (NB) is characterized by enhanced cell survival mediated by TrkB and its ligand, brain derived neurotrophic factor (BDNF); thus reduction in BDNF levels represent a promising strategy to overcome drug-resistance, but how chemotherapics regulate BDNF is unknown. Here, cisplatin treatment in SK-N-BE neuroblastoma upregulated multiple BDNF transcripts, except exons 5 and 8 variants. Cisplatin increased BDNF mRNA and protein, and enhanced translation of a firefly reporter gene flanked by BDNF 5'UTR exons 1, 2c, 4 or 6 and 3'UTR-long. To block BDNF translation we focused on aurora kinases inhibitors which are proposed as new chemotherapeutics. NB cell survival after 24 h treatment was 43% with cisplatin, and 22% by cisplatin+aurora kinase inhibitor PHA-680632, while the aurora kinases inhibitor alone was less effective; however the combined treatment induced a paradoxical increase of BDNF in surviving cells with strong translational activation of exon6-3'UTR-long transcript, while translation of BDNF transcripts 1, 2C and 4 was suppressed. In conclusion, combined cisplatin and aurora kinase inhibitor treatment increases cell death, but induces BDNF overproduction in surviving cells through an aurora kinase-independent mechanism. PMID- 27256408 TI - IF-combined smRNA FISH reveals interaction of MCPIP1 protein with IER3 mRNA. AB - MCPIP1 and IER3 are recently described proteins essential for maintenance of immune homeostasis. IER3 is involved in the regulation of apoptosis and differentiation and has been shown lately to protect activated T cells and macrophages from apoptosis. MCPIP1 is an RNase critical for controlling inflammation-related mRNAs. MCPIP1 interacts with and degrades a set of stem-loop containing mRNAs (including IL-6). Our results demonstrate the involvement of MCPIP1 in the regulation of IER3 mRNA levels. A dual luciferase assay revealed that over-expression of MCPIP1 resulted in a decrease of luciferase activity in the samples co-transfected with constructs containing luciferase CDS attached to IER3 3'UTR. We identified a stem-loop structure similar to that described to be important for destabilization of the IL-6 mRNA by MCPIP1. Examination of IER3 3'UTR sequence, structure and evolutionary conservation revealed that the identified stem-loop is buried within a bigger element. Deletion of this fragment abolished the regulation of IER3 3'UTR-containing transcript by MCPIP1. Finally, using immunofluorescence-combined single-molecule RNA FISH we have shown that the MCPIP1 protein co-localizes with IER3 mRNA. By this method we also proved that the presence of the wild-type NYN/PIN-like domain of MCPIP1 correlated with the decreased level of IER3 mRNA. RNA immunoprecipitation further confirmed the interaction of MCPIP1 with IER3 transcripts in vivo. PMID- 27256409 TI - Counting and Surveying Homeless Youth: Recommendations from YouthCount 2.0!, a Community-Academic Partnership. AB - Communities across the United States are increasing efforts to find and count homeless youth. This paper presents findings and lessons learned from a community/academic partnership to count homeless youth and conduct an in depth research survey focused on the health needs of this population. Over a 4 week recruitment period, 632 youth were counted and 420 surveyed. Methodological successes included an extended counting period, broader inclusion criteria to capture those in unstable housing, use of student volunteers in health training programs, recruiting from magnet events for high risk youth, and partnering with community agencies to disseminate findings. Strategies that did not facilitate recruitment included respondent driven sampling, street canvassing beyond known hotspots, and having community agencies lead data collection. Surveying was successful in gathering data on reasons for homelessness, history in public systems of care, mental health history and needs, sexual risk behaviors, health status, and substance use. Youth were successfully surveyed across housing types including shelters or transitional housing (n = 205), those in unstable housing such as doubled up with friends or acquaintances (n = 75), and those who were literally on the streets or living in a place not meant for human habitation (n = 140). Most youth completed the self-report survey and provided detailed information about risk behaviors. Recommendations to combine research data collection with counting are presented. PMID- 27256410 TI - Awareness and Use of South Asian Tobacco Products Among South Asians in New Jersey. AB - South Asians are the third largest Asian group in the US and among the fastest growing racial groups in New Jersey. Tobacco consumption among South Asians is characterized by several smoked and smokeless tobacco products indigenous to the Indian subcontinent. However, there is a paucity of research on tobacco use behaviors among South Asians in the US. The goal of this study was to examine the awareness and use of South Asian tobacco products such as bidis, gutkha, paan, paan masala, and zarda as well as other potentially carcinogenic products such as supari, their context of use, and their cultural significance among South Asians living in the US. Eight focus groups were conducted with South Asian adults living in Central New Jersey. Overall, participants were aware of a wide variety of foreign and American tobacco products with older South Asians identifying a greater variety of indigenous products compared to younger South Asians. Hookah was consistently recognized as popular among the younger generation while products such as paan or paan masala were more commonly identified with elders. Use of tobacco-related products such as paan and supari were described as common at social gatherings or after meals. In addition, light or social users of South Asian tobacco products, including products not consistently defined as tobacco, may not report tobacco use on a survey. Better understanding of the use of these products among South Asians and how some may classify tobacco usage can inform future research and public health interventions in these communities. PMID- 27256411 TI - Epidemiology of basal and squamous cell carcinoma in Belgium: the need for a uniform and compulsory registration. AB - BACKGROUND: Non-melanoma skin cancer (NMSC) is the most common type of cancer among Caucasians, however, few data exist on its incidence. Because of a sheer volume of these tumours, NMSC is often not systematically registered. OBJECTIVE: To describe and analyse the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in Belgium. METHODS: Incidence data of BCC and SCC, including multiple primary skin tumours in the same patient, were extracted from the Belgian Cancer Registry from 2004 to 2012 (predominantly coming from pathology notifications). Belgian legislation makes cancer registration compulsory for oncological care programmes and for all pathological anatomy laboratories. RESULTS: Between 2004 and 2012, 113 254 BCC and 33 153 SCC cases were reported in Belgium. A total of 130 339 patients had 146 407 tumours. Approximately, 10% of the patients (12 759 patients) had multiple tumours. The world age-standardised incidence rate (WSR) for BCC increased from 36.9 in 2004 to 98.4 per 100 000 person years in 2012 for males and from 34.2 in 2004 to 102.0 in 2012 for females. For SCC, the WSR increased from 14.9 in 2004 to 24.7 in 2012 for males and from 6.8 in 2004 to 13.5 in 2012 for females. CONCLUSIONS: From 2004 to 2012, the incidence of BCC and SCC markedly rose in Belgium, as also seen worldwide. Known causes are increased sun exposure caused by changed sunlight related behaviour (increased outdoor activities and holidays, use of tanning beds and changes in clothing style), ageing and improved registration. Because of their high and increasing incidence, these cancers will have major implications on healthcare planning and preventive measures. Therefore, we recommend compulsory registration, whenever is possible, of BCC and SCC, although it is an ambitious objective, especially in countries with a high burden of these tumours and in countries where registration is currently unavailable. PMID- 27256412 TI - WHO open to "lobbying" by business. PMID- 27256413 TI - Reduction of radiation exposure in cryoballoon ablation procedures: a single centre study applying intracardiac echocardiography and other radioprotective measures. AB - Aims: The population treated with cryoballoon (CB) ablation is relatively young, and radiation protection is of major importance. We aimed to demonstrate that radiation exposure can be markedly reduced by intracardiac echocardiography (ICE) and optimized settings of the X-ray system. Methods and results: We analysed 100 patients undergoing CB pulmonary vein isolation (PVI) for treatment of paroxysmal atrial fibrillation. In 50 consecutive patients (25 male, 59 +/- 13 years; Group 1), we used ICE, skipped PV angiography prior to CB inflation, and avoided fluoroscopy whenever possible. Furthermore, we reduced the frame rate, minimized distance between patient and detector, and consequently applied collimation. These patients were compared with 50 similar preceding patients in Group 2 (29 male, 61 +/- 12 years). Total fluoroscopy time was reduced from 18 +/- 6 min in Group 2 to 12 +/- 5 min in Group 1 (P < 0.001). Moreover, the dose area product was significantly lower (1555 +/- 1219 vs. 4935 +/- 2094 cGycm2, P < 0.001), total freezing time was significantly shortened (1855 +/- 399 vs. 2121 +/- 756 s, P = 0.031), and contrast media use was significantly reduced (66 +/- 25 vs. 109 +/- 27 mL, P < 0.001). At the same time, total procedure duration and complication rates did not differ significantly between both groups. After a 12 months follow-up, a similar percentage of patients was free from recurrences (74% in Group 1 vs. 78% in Group 2, P = 0.640). Conclusion: Radiation exposure in CB PVI can be markedly reduced without prolonging procedure times, affecting the outcome or complication rates. Moreover, ICE seems to shorten total freezing time. PMID- 27256415 TI - Exome sequencing in arrhythmogenic right ventricular cardiomyopathy: a new diagnostic tool? PMID- 27256414 TI - Venous thromboembolism in patients with implantable cardioverter-defibrillators. AB - Aims: To examine the incidence of venous thromboembolism (VTE) and its risk factors among patients with implantable cardioverter-defibrillators (ICDs). Methods and results: All first-time ICD recipients in Denmark during 2000-12 were identified from medical databases. Incident VTEs were ascertained, overall and according to gender, age, Charlson Comorbidity Index score (no, moderate, or severe comorbidity), prior pacemaker or cardiac resynchronization therapy (CRT-D) implantation, and ICD type (single-chamber, dual-chamber, or CRT-D). We computed the risk of VTE within 3 months and 5 years of implantation, taking death into account as a competing risk. We used Cox proportional hazards regression to compute hazard ratios as estimates of incidence rate ratios (IRRs). Among 8132 ICD recipients, 136 VTEs were diagnosed during up to 13 years of follow-up (median = 3.0 years). The VTE incidence rate was thus 4.5 per 1000 person-years [95% confidence interval (CI): 3.7-5.2]. Venous thromboembolism risk was 0.3% (95% CIs ranging from 0.1 to 0.7%) within 3 months following ICD implantation regardless of comorbidity level. Within 5 years following implantation it was 1.4% (95% CI: 0.8-2.3%), 1.3% (1.0-1.8%), and 3.2% (95% CI: 2.4-4.1%) for patients with no, moderate, and severe comorbidity, respectively. Overall, severe comorbidity conferred a 2.7-fold higher incidence rate ratio than no comorbidity (95% CI: 1.6-4.6). Incidence rate ratios did not differ by gender, age, or ICD type. Conclusion: Three-month risk of VTE following ICD implantation was 0.3% regardless of comorbidity level. Five-year risk of VTE following ICD implantation was 1.9% and more than twice as high for patients with severe comorbidity as for patients without comorbidity. PMID- 27256416 TI - Influence of patients' age at implantation on mortality and defibrillator shocks. AB - Aims: Patients have increasing comorbidities and competing causes of death with advancing age, raising questions about the effectiveness of the implantable cardioverter defibrillators (ICD) in older age. We therefore investigated the effect of patients' age at initial device implantation on all-cause mortality and on the risk of ICD shocks in single-chamber (V-ICD), dual-chamber (D-ICD), and cardiac resynchronization therapy defibrillator (CRT-D) recipients. Methods and results: We reviewed de-identified records of 67 128 ICD recipients enrolled in the Boston Scientific ALTITUDE database of remote monitored patients [V-ICD (n = 11 422), D-ICD (n = 23 974), and CRT-D (n = 31 732)]. Over a mean follow-up of 2.3 +/- 1.4 years, patients in all ICD groups had increased all-cause mortality but decreased risk of defibrillator shocks and/or anti-tachycardia pacing per 10 year increase in age. Compared with the youngest age group (<50 years), patients in the oldest age group (>=80 years) had a 6.8-fold, 5.9-fold, and 3.4-fold increase in all-cause mortality (P < 0.001 for all comparisons) and a 31, 45, and 53% decrease in the risk of ICD shock (P <= 0.002 for all comparisons) for the V ICD, D-ICD, and CRT-D groups, respectively. Conclusion: Older recipients of standard and CRT defibrillators have higher mortality but fewer ICD shocks and/or therapies compared with younger patients. These data highly suggest less benefit of ICD therapy with increasing age, presumably because of competing risks of non arrhythmic mortality. The role of defibrillator therapy in older patients may need to be evaluated with randomized controlled trials. PMID- 27256417 TI - Provision of magnetic resonance imaging for patients with 'MR-conditional' cardiac implantable electronic devices: an unmet clinical need. AB - Aims: Increasing need for magnetic resonance imaging (MRI) has driven the development of MR-conditional cardiac implantable electronic devices (CIEDs; pacemakers and defibrillators); however, patients still report difficulties obtaining scans. We sought to establish current provision for MRI scanning of patients with CIEDs in England. Methods and results: A survey was distributed to all hospitals in England with MRI, to assess current practice. Information requested included whether hospitals currently offer MRI to this patient group, the number and type of scans acquired, local safety considerations, complications experienced and perceived obstacles to service provision in those departments not currently offering it. Responses were received from 195 of 227 (86%) of hospitals surveyed. Although 98% of departments were aware of MR-conditional devices, only 46% (n = 89) currently offer MRI scans to patients with CIED's; of these, 85% of departments perform <=10 scans per year. No major complications were reported from MRI scanning in patients with MR-conditional devices. Current barriers to service expansion include perceived concerns regarding potential risk, lack of training, logistical difficulties, and lack of cardiology support. Conclusion: Provision of MRI for patients with CIEDs is currently poor, despite increasing numbers of patients with MR-conditional devices and extremely low reported complication rates. PMID- 27256418 TI - Implanted defibrillators in trouble: initial device misclassification leads to correct diagnosis-a case series. AB - Aims: Supraventricular tachycardia, mistakenly diagnosed as ventricular tachycardia, may lead to inappropriate ICD therapy. Inappropriate ICD therapy associates with increased morbidity and mortality. A reduction of inappropriate therapy is therefore desired. Methods and results: We present three different cases that beautifully illustrate the diagnostic possibilities of stored electrograms. Initial differential diagnoses in all three patients included ventricular tachycardia, focal atrial tachycardia, atrio-ventricular re-entry tachycardia, and atrio-ventricular nodal re-entry tachycardia. The first case was diagnosed as atrio-ventricular nodal re-entry tachycardia. In the second case, atrio-ventricular re-entry tachycardia was revealed. Ectopic atrial tachycardia was the reason for inappropriate therapy in the third patient. Conclusion: Thorough analysis of stored electrograms yielded correct diagnosis in all cases, which subsequently was confirmed by electrophysiological study. PMID- 27256419 TI - Magnetic resonance imaging in patients with cardiac implanted electronic devices: focus on contraindications to magnetic resonance imaging protocols. AB - Aims: Magnetic resonance imaging (MRI) has been reported to be safe in patients with cardiac implantable electronic devices (CIED) provided a specific protocol is followed. The objective of this study was to assess whether this is also true for patients excluded from published protocols. Methods and results: A total of 160 MRIs were obtained in 142 consecutive patients with CIEDs [106 patients had an implantable cardioverter defibrillator (ICD) and 36 had a pacemaker implanted] using an adapted, pre-specified protocol. A cardiac MRI was performed in 95 patients, and a spinal/brain MRI was performed in 47 patients. Forty-six patients (32%) had either abandoned leads (n = 10), and/or were pacemaker dependent with an implanted ICD (n = 19), had recently implanted CIEDs (n = 1), and/or had a CIED device with battery depletion (n = 2), and/or a component of the CIED was recalled or on advisory (n = 32). No major complications occurred. Some device parameters changed slightly, but significantly, right after or at 1-week post-MRI without requiring any reprogramming. In one patient with an ICD on advisory, the pacing rate changed inexplicably during one of his two MRIs from 90 to 50 b.p.m. Conclusion: Using a pre-specified protocol, cardiac and non-cardiac MRIs were performed in CIED patients with pacemaker dependency, abandoned leads, or depleted batteries without occurrence of major adverse events. Patients with devices on advisory need to be monitored carefully during MRI, especially if they are pacemaker dependent. PMID- 27256420 TI - Pulmonary vein reconnection predicts good clinical outcome after second catheter ablation for atrial fibrillation. AB - Aims: Although electrically reconnected pulmonary veins (PV) are the main mechanism of atrial fibrillation (AF) recurrence, PV isolation (PVI) is well preserved in certain patients who undergo a repeat procedure. We explored the association between PV reconnection and clinical outcomes after a second ablation. Methods and results: This observational cohort study included 143 patients (79.0% male, 56.1 +/- 10.0 years old, 65.0% paroxysmal AF) who underwent a second procedure. Pulmonary vein isolation was well-maintained in 52 patients (PVP- group, 36.4%), although the remaining 91 patients showed PV reconnection (PVP+ group). After confirming PVI, we mapped non-PV triggers and conducted trigger ablation or additional linear ablation at redo-procedures. The proportion of females was higher (P = 0.030), and redo-ablation timing after the de novo procedure was later (P = 0.039) in the PVP- group than in the PVP+ group. Additional linear ablations were more likely to be performed in the PVP- group (90.4 vs. 61.5%, P < 0.001). During the 18.4 +/- 10.2 month follow-up after the redo-ablation, the PVP+ group showed a lower clinical recurrence rate than the PVP- group (log-rank P = 0.011). The number of reconnected PVs was independently associated with a lower recurrence of AF after the redo-ablation in the total study population (HR 0.56, 95% CI 0.34-0.95, P = 0.032), particularly for patients with paroxysmal AF (HR 0.41, 95% CI 0.19-0.87, P = 0.021). Conclusion: Among patients who underwent redo-AF ablation, those with more PV reconnections showed better clinical outcomes than those with fewer PV reconnections. The mechanism of AF recurrence might be different in patients with lower numbers of PV reconnections during redo-procedures. PMID- 27256421 TI - Prognosis of high sinus heart rate after catheter ablation for atrial fibrillation. AB - Aims: Although atrial fibrillation (AF) catheter ablation increases sinus heart rate (HR), its mechanism and prognosis have not yet been clearly elucidated. We hypothesize that post-AF ablation high sinus HR (PA-HSR) is associated with a better clinical outcome of AF ablation without adverse cardiac effects. Methods and results: We studied 991 AF patients (75% male, 58 +/- 11 years old, 70% paroxysmal AF) with HR variability (HRV) at 3 months and 1 year after catheter ablation, and pre- and post-1-year echocardiograms. Post-AF ablation high sinus HR was defined as an average HR greater than 2 SD (>=92 bpm) as measured by 24 h Holter. (1) Average HR increased significantly (P< 0.001), and PA-HSR was observed in 28 patients (2.8%) 3 months after AF ablation. At 1 year after catheter ablation, 21% were taking beta-blockers and 36% maintained an average HR of >=92 bpm. (2) Post-AF ablation high sinus HR was independently associated with pre-procedural high average HR (OR 1.097; 95% CI 1.029-1.169, P= 0.005), high left atrium (LA) electrogram voltage (OR 3.545; 95% CI 1.183-10.618, P= 0.024), and reduced root mean square of differences between successive NN intervals (rMSSD) at 3 months HRV (OR 0.959; 95% CI 0.919-0.999, P= 0.047). (3) At 1 year echocardiography, size reduction of LA (P= 0.055) or LV (P= 0.372) and the improvement in ejection fraction (P= 0.529) were not significantly different between patients with PA-HSR and those without. (4) Throughout 27 +/- 17 months of follow-up, patients with PA-HSR showed significantly lower clinical recurrence than those without (log rank, P= 0.020). Conclusion: Post-AF ablation high sinus HR was observed in patients with smaller LA size and higher LA electrogram voltage and significant vagal modulation without adverse cardiac effects. Post-AF ablation high sinus HR was associated with a significantly lower clinical recurrence of AF after catheter ablation. PMID- 27256424 TI - Collateral damage after endocardial catheter ablation. PMID- 27256423 TI - Left-ventricular geometry and risk of sudden cardiac arrest in patients with preserved or moderately reduced left-ventricular ejection fraction. AB - Aims: The majority of sudden cardiac arrests (SCAs) occur in patients with left ventricular (LV) ejection fraction (LVEF) >35%, yet there are no methods for effective risk stratification in this sub-group. Since abnormalities of LV geometry can be identified even with preserved LVEF, we investigated the potential impact of LV geometry as a novel risk marker for this patient population. Methods and results: In the ongoing Oregon Sudden Unexpected Death Study, SCA cases with archived echocardiographic data available were prospectively identified during 2002-15, and compared with geographical controls. Analysis was restricted to subjects with LVEF >35%. Based on established measures of LV mass and relative wall thickness (ratio of wall thickness to cavity diameter), four different LV geometric patterns were identified: normal geometry, concentric remodelling, concentric hypertrophy, and eccentric hypertrophy. Sudden cardiac arrest cases (n = 307) and controls (n = 280) did not differ in age, sex, or LVEF, but increased LV mass was more common in cases. Twenty-nine percent of SCA cases presented with normal LV geometry, 35% had concentric remodelling, 25% concentric hypertrophy, and 11% eccentric hypertrophy. In multivariate model, concentric remodelling (OR 1.76; 95%CI 1.18-2.63; P = 0.005), concentric hypertrophy (OR 3.20; 95%CI 1.90-5.39; P < 0.001), and eccentric hypertrophy (OR 2.47; 95%CI 1.30-4.66; P = 0.006) were associated with increased risk of SCA. Conclusion: Concentric and eccentric LV hypertrophy, but also concentric remodelling without hypertrophy, are associated with increased risk of SCA. These novel findings suggest the potential utility of evaluating LV geometry as a potential risk stratification tool in patients with preserved or moderately reduced LVEF. PMID- 27256426 TI - Brockenbrough needle markedly deformed by vein tortuosity. PMID- 27256427 TI - Last call on nMARQTM safety. PMID- 27256428 TI - Late asymptomatic atrial lead perforation, a fortuitous finding during lead extraction using thoracoscopic surveillance: a case report and review of the literature. AB - A 61-year-old male patient was referred for lead extraction of an infected two chamber pacemaker system first implanted 18 years ago. A new atrial lead was implanted 9 years later because of loss of capture of the original lead. Video assisted thoracoscopic surgery (VATS) that we use in high-risk cases showed extensive fibrous adhesion between the right atrium wall and the right lung. Dissection of the adhesion revealed the presence of an atrial lead perforated into the lung. After cutting off the lead tip, the residual lead was removed endovascularly from the subclavian site. A literature review of 25 reported cases of late atrial lead perforation was added to the findings in our case report. PMID- 27256429 TI - Atypical lower loop reentrant tachycardia associated with multiple hepatic veins. PMID- 27256430 TI - An investigation of the factors effecting high-risk individuals' decision-making about prophylactic total gastrectomy and surveillance for hereditary diffuse gastric cancer (HDGC). AB - Hereditary diffuse gastric cancer has an early onset and poor prognosis, therefore, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties. Patients not ready or fit to undergo gastrectomy, or in whom the genetic testing result is unknown or ambiguous, are offered surveillance. Little is known about the factors that influence decisions to undergo or decline PTG, making it difficult to provide optimal support for those facing these decisions. Qualitative interviews were carried out with 35 high-risk individuals from the Familial Gastric Cancer Study in the UK. Twenty-seven had previously undergone PTG and eight had been identified as carrying a pathogenic CDH1 mutation but had declined surgery at the time of interview. The interviews explored the experience of decision-making and factors influencing risk-management decisions. The data suggest that decisions to proceed with PTG are influenced by a number of potentially competing factors: objective risk confirmation by genetic testing and/or receiving a positive biopsy; perceived familial cancer burden and associated risk perceptions; perceptions of post-surgical life; an increasing inability to tolerate endoscopic procedures; a concern that surveillance could miss a cancer developing and individual's life stage. These findings have implications for advising this patient group. PMID- 27256431 TI - Utility of chromogranin A, pancreatic polypeptide, glucagon and gastrin in the diagnosis and follow-up of pancreatic neuroendocrine tumours in multiple endocrine neoplasia type 1 patients. AB - OBJECTIVE: Pancreatic neuroendocrine tumours (PNETs) are the major source of disease-specific mortality in multiple endocrine neoplasia type 1 (MEN1) patients. Chromogranin A (CgA), pancreatic polypeptide (PP), glucagon and gastrin have some diagnostic value in sporadic PNETs, but there is very little evidence for their efficacy in diagnosing PNETs in MEN1 patients. DESIGN: We performed a retrospective chart review of the existing MEN1 database in our institution. PATIENTS: One hundred and thirteen patients were eligible for diagnostic value analysis of tumour markers. Patients were excluded if measurement of tumour markers was missing, either 3 months prior to PNET diagnosis (PNET patients) or prior to abdominal imaging (non-PNET patients). MEASUREMENTS: Clinicopathologic characteristics and of tumour marker measurements were analysed. RESULTS: Of 293 confirmed MEN1 cases, 55 PNETs and 58 non-PNETs met inclusion criteria. The area under the curve (AUC) for CgA, PP, glucagon and gastrin in MEN1 cases was 59.5%, 64.1%, 77.0% and 75.9%, respectively. The AUC for the combination of CgA, PP and gastrin was 59.6%. PP, but not CgA, glucagon or gastrin was significantly associated with both age and PNET functional status (P = 0.0485 and 0.0188, respectively). No markers were significantly associated with sex, PNET size, tumour number, tumour location, American Joint Committee on Cancer (AJCC) stage, presence of lymph node metastasis, lymphovascular invasion or overall survival. CgA values were not significantly lower following PNET resection than pre operatively (P = 0.554). CONCLUSIONS: The value of blood markers for diagnosing PNETs in MEN1 patients is relatively low, even when used in combination. PMID- 27256432 TI - Evaluation of Gold's nomogram for predicting recurrence-free survival in gastrointestinal stromal tumors in Indian patients. AB - Gold described a nomogram for prediction of recurrence-free survival (RFS) after surgery for gastrointestinal stromal tumors (GIST). This retrospective study was intended to evaluate the utility of this nomogram for predicting a 2-year RFS in our patients. Twenty-eight consecutive eligible patients from January 2009 to January 2013 who underwent R0 resection and had histopathologically proven GIST were included in the study. Nomogram predicted RFS was compared with observed RFS in four groups as in the National Institutes of Health (NIH)-Fletcher classification. Calibration was assessed by plotting the predicted probabilities of RFS against the actual outcome. For validation of the nomogram, the graph obtained should be closer to the 45-degree line. The observed overall 2-year RFS was 85.7 % (24 patients). Four patients had recurrence within 2 years. The observed RFS was 87.5 %, 77.8 %, 90 %, and 100 % in the high, intermediate, low, and very low risk groups, respectively. The nomogram predicted the 2-year RFS was 40 %, 84.8 %, 88.6 %, and 90 % for high, intermediate, low, and very low risk groups, respectively. Thus, the predicted probabilities of the 2-year RFS in intermediate, low, and very low risk groups were similar to the observed outcomes. However, for the high risk group, the observed RFS was better than predicted RFS. This variation in the high risk group may be due to the use of adjuvant imatinib in our study. PMID- 27256433 TI - Prevalence and predictive factors for development of splenic artery aneurysms in cirrhosis. AB - BACKGROUND AND AIMS: Splenic artery aneurysm (SAA) rarely occurs in the general population. Its increased incidence has been reported in cirrhosis. The aim of this retrospective study was to identify prevalence and predictive factor development of SAA in patients with cirrhosis. METHODS: All patients with cirrhosis who were treated in our clinics between 2010 and 2014 were included in the study. Demographic features and clinical and laboratory findings were reviewed. Four-phase computerized tomography (CT) was used for identifying SAA. Imaging was reviewed for the presence of SAA as well as hepatic artery, portal vein, splenic artery, splenic vein, liver parenchyma, and intraabdominal cavity were evaluated. RESULTS: A total of 171 patients (age 55+/-13.9, 109 men) were included in the study. There was SAA in 27 (15.7 %) patients. Mean diameter of aneurysm was 11.66 (range, 6.06-27.1) mm. Aneurysm was located in the distal part of splenic artery in 20 (74 %) patients and solitary in 24 (88.8 %), and asymptomatic in all patients. Patients with SAA had larger portal vein and splenic vein compared to patients without SAA (15.3+/-3.9 vs. 13.1+/-2.9 mm, p=0.001; and 12.5+/-4.4 vs. 9.6+/-2.7 mm, p<0.001, respectively). We identified positive correlation between development of SAA and splenic vein diameter [hazard ratio (HR) =1.23; 95 % confidence interval (CI) 0.97-1.57; p = 0.009] and negative correlation between hepatic artery diameter and development of SAA HR = 0.46; 95 % CI 0.25-0.85; p = 0.002). CONCLUSION: SAA occurred in a significant proportion of patients with cirrhosis, and enlargement of the splenic vein seemed to be a predictive factor for the development of SAA. PMID- 27256435 TI - Triple Combination Therapy for Global Cardiovascular Risk: Atorvastatin, Perindopril, and Amlodipine. AB - Statins, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers (CCBs) have markedly changed the clinical progression of patients with coronary artery disease (CAD). The goal of this paper is to review the rationale and evidence for combining these three drug classes in hypertensive patients with hypercholesterolemia or CAD. Data sources include a literature search for publications on the use of a statin combined with various antihypertensive drugs in patients with hypertension and hypercholesterolemia or stable CAD. Hypercholesterolemia and hypertension constitute major physiological risk factors of ischemic heart disease. Current guidelines recommend a global approach to risk management, using agents that address as many risk factors as possible. Dual combination therapies are an important component of guideline-recommended therapy in hypertension. Our review of the literature indicates that triple therapy with a statin, ACE inhibitor, and CCB is associated with a significant reduction in major cardiovascular events. For example, a post hoc analysis in 1056 patients with stable CAD participating in the EUROPA trial indicated that the addition of perindopril to a CCB and a lipid-lowering agent was associated with a 46 % reduction in the composite of cardiovascular death, myocardial infarction, and resuscitated cardiac arrest (p = 0.023). In addition, single pill formulations are known to result in better adherence to the treatment. Single-pill formulations that combine a statin, an ACE inhibitor, and a CCB appear to offer an effective approach to the management of global cardiovascular risk. PMID- 27256437 TI - [Expert concensus on quantitative fluorescent polymerase chain reaction in the prenatal diagnosis of aneuploidies]. PMID- 27256436 TI - Analysis of Cell Cycle Status of Murine Hematopoietic Stem Cells. AB - Hematopoietic stem cells (HSC) act as paradigmatic tissue-specific adult stem cells. While they are quiescent in steady-state conditions, they enter the cell cycle and proliferate in stress conditions and during tissue regeneration. Therefore, analysis of cell cycle status of HSC is crucial for understanding their biology. However, due to low number of HSC in tissue and need to use many surface markers for their identification, analysis of their cycle status is technically complicated. Here, we presented our simple strategy to analyze cell cycle of strictly defined LKS CD48(-)CD150(+)CD34(-) HSC, together with Ki67 and DAPI staining by flow cytometry. PMID- 27256434 TI - Liver involvement in human immunodeficiency virus infection. AB - The advances in management of patients with acquired immunodeficiency syndrome (AIDS) with highly effective anti-retroviral therapy (HAART) have resulted in increased longevity of patients with human immunodeficiency virus (HIV) infection. AIDS-related illnesses now account for less than 50 % of the deaths, and liver diseases have emerged as the leading cause of death in patients with HIV infection. Chronic viral hepatitis, drug-related hepatotoxicity, non alcoholic fatty liver disease, and opportunistic infections are the common liver diseases that are seen in HIV-infected individuals. Because of the shared routes of transmission, co-infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are very common in HIV-infected persons. Hepatitis C is the most common viral hepatitis seen in HIV-infected patients. With the availability of directly acting agents, treatment outcome of HCV is comparable to that seen in non HIV infected patients. Careful monitoring is required for drug interactions and drug induced hepatotoxicity and modification of drugs should be done where necessary. The results of liver transplantation in select HIV-infected patients can be comparable with those of HIV-negative patients. PMID- 27256438 TI - [Prenatal diagnosis of chromosome abnormalities and nine microdeletion syndromes using both traditional karyotyping and BoBs]. AB - OBJECTIVE: To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on Beads (BoBs) technique. METHODS: From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. RESULTS: Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs; while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. CONCLUSION: Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service. PMID- 27256439 TI - [Clinical treatment of infective endocarditis with vegetations in pregnant women and the outcomes of gestation]. AB - OBJECTIVE: To investigate the clinical treatment of infective endocarditis with vegetations in pregnant women and the outcomes of the gestation. METHODS: Nine cases of pregnant women diagnosed as infective endocarditis with vegetations in Beijing Anzhen Hospital, Capital Medical University from January 2001 to October 2015 were enrolled in retrospective analysis. Consultations were held by doctors from department of obstetrics, anesthesiology, cardiology, cardial surgery and extracorporeal circulation to decide the individualized treatment plan for the 9 cases of pregnant women after admissions. Clinical treatments including general treatment, anti-infection treatment, cardiac surgery, and termination of pregnancy surgery were completed through collaboration among related departments. The clinical characters, therapeutic regimens, maternal and neonatal outcomes of the 9 cases were analyzed. RESULTS: (1) Clinical characters: the ages of the 9 cases of pregnant women were from 25 to 36 years old. The onset gestational ages were from 19 to 36 weeks. CLINICAL SYMPTOMS: fever, cough, sputum and progressive anemia were the main symptoms. Patients had cyanosis of lips, could not lie on the back or even be orthopnea, when heart failure happened. Heart murmur was audible and splenomegaly was touched in physical examination. Blood cultures were positive. Basic heart disease types: 7 cases of congenital heart diseases included 2 cases of aortic insufficiency, 1 case of mitral insufficiency, 1 case of patent ductus arteriosus, 1 case of right ventricular outflow tract stenosis and 2 cases of ventricular septal defect.Two cases of rheumatic heart diseases included 1 case of mitral stenosis, 1 case of mitral stenosis after artificial disc changed and jammed. According to endocardial vegetations attached position there were 3 cases of mitral valve vegetations, 2 cases of pulmonary valve vegetations, 3 cases of aortic vegetations and 1 case of right ventricular outflow tract neoplasm. Preoperative heart function classification: 1 case of level II, 3 cases of level III, 5 cases of level IV. (2) TREATMENTS: general treatment included oxygen uptake, rest in bed, cardiac strengthen and diuretic therapy, etc. Combined and adequate antibiotics were applied in anti-infection treatment according to drug sensitive test. Nine cases of pregnant women were all performed surgical treatment of heart diseases and removal of the endocardial vegetations. Caesarean sections were performed for 2 cases in second trimester and for 7 cases in last trimester. Cardiac surgery and caesarean section were operated in 6 cases at the same time among 22-34 weeks of pregnancy. Cardiac surgery were respectively operated in 2 cases 11 days and 32 days after the caesarean section at 33, 37 weeks of pregnancy. While Cardiac surgery was operated (at 26 weeks of pregnancy) before the caesarean section (at 37 weeks of pregnancy) in another 1 case. (3) Maternal and neonatal outcomes: 7 cases of pregnant women were rescued successfully, while 2 cases of pregnant women were death. Postoperative heart function classification: 1 case of level I, 2 cases of level II, 4 cases of level III and 2 cases of level VI. Neonatal survivals were 6 cases including 2case of full-term infants, 4 cases of preterm infants. Stillbirth or neonatal death were 3 cases, which included 2 cases performed caesarean section in second trimester and 1 case of very low weight infant who was given up treatment by family because of severe asphyxia. Followed up periods were from 1 to 7 years with an average time of (2.0+/-1.6) years. Infants and young children grew and developed well during the period of follow up. CONCLUSIONS: The risk is extremely high of pregnancy with infective endocarditis with vegetations. But there is still a way to save the maternal and neonatal life by using a multidisciplinary collaboration formulation and implementation of individualized treatment plan and selecting the appropriate time for heart surgery and the termination of pregnancy. PMID- 27256440 TI - [Relationship between the thyroid autoimmunity and the risk of preterm birth in pregnant women: a meta-analysis]. AB - OBJECTIVE: To evaluate the relationship between thyroid autoimmunity and the risk of preterm birth. METHODS: Literature search was done among PubMed, Embase, Wanfang Medical Database, China Academic Journal Network Publishing Database and China Biology Medicine disc from Jan. 1(st) 1980 to July 31(st), 2015. (1) Literature were extracted according to inclusion and exclusion standards, and the quality of the extracted literature were evaluated by Newcastle-Ottawa Scale (NOS). (2) Meta-analysis was performed by RevMan 5 software formulated by using the Cochrane library databases. Various heterogeneity of the research was inspected firstly. According to the results of the inspection a certain effect model was selected (including fixed effects model, the random effects model) to be utilized in merger analysis. In this study pregnant women with both thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin (TG-Ab) positive were defined as thyroid antibody positive pregnant women. Pregnant women with only TPO-Ab positive were defined as TPO-Ab positive pregnant women. Then the relationship of antibody positive and the risk of a preterm birth was analyzed respectively. RESULTS: (1) Ten cohort studies were enrolled, of which NOS scale score were 7 or higher. All the studies are of medium quality and above. A total of 1 322 cases of preterm birth occurred among 19 910 pregnant women. (2) Positive thyroid autoantibodies did not increase the risk of preterm birth in euthyroid pregnant women (OR=1.41, 95%CI: 0.83-2.40, P=0.200) or in pregnant women with hypothyroidism (OR=0.68, 95% CI: 0.32-1.44, P=0.310) . Positive TPO-Ab in euthyroid pregnant women increase the risk of preterm birth significantly (OR=2.08, 95%CI: 1.09-3.97, P=0.030), but positive TPO-Ab in pregnant women with hypothyroidism did not increase the risk of preterm birth significantly (OR=1.21, 95%CI: 0.65-2.24, P=0.550). CONCLUSION: Positive TPO-Ab is an independent risk factor of preterm birth in euthyroid pregnant women. PMID- 27256441 TI - [A prospective cohort study on effects of levonorgestrel-releasing intrauterine system for adenomyosis with severe dysmenorrhea]. AB - OBJECTIVE: To investigate treatment effects of levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis with severe dysmenorrhea in a prospective cohort study. METHODS: From December 2006 to December 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in outpatient or inpatient clinics of Peking Union Medical College Hospital were given the treatment of LNG-IUS. Before and after placement of LNG-IUS, all the patients' parameters were recorded prospectively, including symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, carrying status of LNG-IUS, menstruation patterns and adverse effects. Changes of scores and patterns of pain during follow-up were analyzed. RESULTS: Totally 1 100 women meets inclusion criteria, among which 640 cases (58.18%, 640/1 100) had severe dysmeorrhea, with median follow-up period of 35 months (range 1-60 months), and accumulative carrying rate of 65% at 60 months follow-up. After placement of LNG-IUS, scores of pain and ratio of severe dysmenorrhea had decreased significantly compared with baselines (all P<0.01), the scroes of visual analog scale (VAS) were 8.1+/-0.9, 5.5+/-2.4, 4.6+/-2.4, 3.3+/-2.2, 2.2+/ 2.1, 2.2+/-1.8, 1.4+/-1.6 and 1.3+/-1.3 at 0, 3, 6, 12, 24, 36, 48 and 60 months respectively. During 36 months after placement of LNG-IUS, scores of pain had improved significantly compared with preceding period (all P<0.01). We found no universal dependent factors predicting improvement of pain, which was neither relevant with simultaneous changes of menstruation patterns nor adverse effects (all P>0.05). CONCLUSION: LNG-IUS is effective for adenomyosis of severe dysmenorrhea. Improvement of pain is independent on patients characters, menstruation patterns or adverse effects. PMID- 27256442 TI - [Spontaneous ovulation in in vitro fertilization-embryo transfer cycles using gonadotropin-releasing hormone antagonist: a large-sample retrospective study]. AB - OBJECTIVE: To investigate the premature spontaneous ovulation rates in in vitro fertilization-embryo transfer (IVF-ET) cycles using gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH a), as well as the risk factors for premature spontaneous ovulation. METHODS: The rates of premature spontaneous ovulation in a total of 10 612 cycles using GnRH ant or GnRH-a were compared. Matched case-controlled study and binary logistic regression model were conducted to analyze the risk factors for premature spontaneous ovulation. RESULTS: The spontaneous ovulation rate in the whole for GnRH-a cycles was 0.15% (13/8 514), compared with a 1.62% (34/2 098) in GnRH-ant cycles (P<0.01). Further matched controlled study and regression analyze found out that higher basal FSH level was a predominant risk and prediction factor for spontaneous ovulation (OR=1.20, P=0.009). CONCLUSIONS: In GnRH-ant cycles, spontaneous ovulation rate is about 10 times than which in GnRH-a cycles. Diminished ovarian function is a predominate risk factor for premature spontaneous ovulation. PMID- 27256443 TI - [Exploratory and confirmatory factor analyses for testing validity and reliability of the Chinese language questionnaire for urinary incontinence diagnosis]. AB - OBJECTIVE: To translate questionnaire for urinary incontinence diagnosis (QUID) into Chinese and to test its reliability and validity. METHODS: The English version of QUID was translated into Chinese. The clinaical data of 95 patinents with urinary incontinence who were test by urinary dynamic study in Peking Union Medical College Hospital from May 2014 to May 2015 were analyzed prospectively. The reliability of QUID was evaluated by completing QUID twice. The validity of QUID was evaluated by the standard of urinary dynamic study. RESULTS: Internal consistency (Cronbach alpha) of the items that pertained to stress urinary incontinence (SUI) and to urge urinary incontinence (UUI) were 0.91 and 0.89, respectively. Test-retest reliability (Kappa) was 0.795 and criterion validity (Kappa) was 0.62. Sensitivity and specificity were 83% (43/52) and 86% (37/43), respectively, for SUI, and 72% (13/18) and 86% (66/77), respectively, for UUI. CONCLUSIONS: QUID has good reliability and validity. It could be used in Chinese urinary incontinence women. PMID- 27256444 TI - [Clinical observation of partial pancreatectomy as part of primary cytoreductive surgery in advanced epithelial ovarian cancer]. AB - OBJECTIVE: The aim of this study is to evaluate the safety and efficacy of partial pancreatectomy as part of primary cytoreductive surgery in advanced epithelial ovarian cancer (EOC). METHODS: A total of 8 patients were recruited in this study who underwent partial pancreatectomy during the primary cytoreductive surgeries for advanced EOC in Fudan University Shanghai Cancer Center from April 2009 to July 2015. Their clinicopathological characteristics, diameter of metastatic tumors, the scope of cytoreductive surgeries, residual diseases after cytoreductive surgeries, postoperative complications and survival situation were retrospective analyzed. RESULTS: (1) Clinicopathological characteristics: the median age of these patients was 58 years old (range: 39-63 years old) . The median value of preoperative serum CA125 was 1 688 kU/L (range: 119-5 000 kU/L) . The median diameter of metastatic tumors involved in pancreatic body or tail was 4.5 cm (range: 3-10 cm). All the tumors from the 8 patients were confirmed to be high-grade serous carcinoma. Four patients were staged as International Federation of Gynecology and Obstetrics (FIGO) IV, and the other 4 patients were staged as FIGO IIIc. (2) Tumor metastases and the scope of cytoreductive surgeries: all of these 8 patients had widely disseminated ovarian cancer, with involvement of upper abdominal, middle abdominal and pelvic cavity. Each patient underwent extensive intra-abdominal cytoreductive surgeries, including hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic peritonectomy, splenectomy, partial pancreatectomy. Each patient had cytoreductive surgeries of 9.6 different sites on average. Of all 8 patients who underwent partial pancreatectomy, 7 patients had pancreatic tails removed; the other 1 patient had pancreatic body and tail removed. The median volume of blood loss during surgery was 1 350 ml (range: 300-3 500 ml) , blood transfusion was performed in 7 patients with the median volume of 1 150 ml (range: 500-1 800 ml). (3) Residual diseases after cytoreductive surgeries: optimal cytoreduction was achieved in all patients, with microscopic residual disease in 3 patients, residual tumors diameter < 0.5 cm in 3 patients, and residual tumors diameter between 0.5 and 1 cm in 2 patients. (4) Postoperative complications: 4 patients suffered from complications including pancreatic leakage (2/8), intraperitoneal hemorrhage (1/8) and pancreatic pseudocyst accompanied by infection (1/8). These complications were treated successfully by conservative managements. (5) Survival situation: during the median follow-up duration of 17 months (ranged from 2 to 46 months), 5 patients were still alive until the end of follow-up, including 4 cases under treatment and 1 case survived 29 months without relapse after treatment. Three patients were respectively died in 5, 20 and 46 months after surgery. CONCLUSION: There is a higher risk of postoperative complications of pancreas resection as part of primary cytoreductive surgery in advanced epithelial ovarian cancer, but the resection of pancreatic metastases and part of the pancreas is feasible and necessary. PMID- 27256445 TI - [Clinical characters of pre-malignant and malignant polyp in postmenopausal women and the diagnostic value of hysteroscopy]. AB - OBJECTIVE: To investigate the clinical characteristics of pre-malignant and malignant polyps in postmenopausal patients and to evaluate the diagnositic value of hysteroscopy in this disease. METHODS: From June 2005 to October 2014, 403 postmenopausal patients with polyps were treated in the Gynecologic Minimally Invasive Center, Beijing Obstetrics and Gynecology Hospital. There were 27 patients including 22 patients with pre-malignant and 5 patients with malignant polyps. All malignant lesions were endometrioid adenocarcinoma. The clinical data were retrospectively analyzed. Based on pathology, the diagnostic value of hysteroscopy was evaluated. RESULTS: (1) CLINICAL CHARACTERISTICS: there were 27 cases with pre-malignant and malignant polyps (group 1) and 376 cases with benign polyps (group 2). Compared the two groups, the average age was (60+/-8) vs (58+/ 6) years old, the period of menopause was (9.8+/-8.1) vs (8.3+/-6.9) years. Thirteen cases (48.1%, 13/27) in group 1 and 159 cases (42.3%, 159/376) in group 2 had clinical symptoms including postmenopausal bleeding and vaginal discharge. Twelve cases (44.4%, 12/27) in group 1 and 140 cases (37.2%, 140/376) in group 2 were with hypertension. Five cases (18.5%, 5/27) in group 1 and 43 cases (11.4%, 43/376) in group 2 were with diabetes. The measures above were no significant differences (P>0.05) (2) Ultrasound features: the average thick of endometrium in group 1 and group 2 were respectively (1.3+/-0.7) and (0.8+/-0.4) cm, which had statistical significance (t=4.98, P=0.001). (3) Hysteroscopic diagnosis: the average diameters of polyp in group 1 and group 2 were respectively (2.4+/-1.0) and (1.6+/-1.0) cm, which had statistical significance (t=2.93, P=0.004). Six cases in group 1 were diagnosed by hysteroscopy including 4 cases of malignant polyp and 2 cases of pre-malignant polyp. The sensitivity, specificity, positive predictive value, negative predictive value and the accuracy were 22.2% (6/27), 100.0% (376/376), 100.0% (6/6), 94.7% (376/397) and 94.8% (382/403), respectively. CONCLUSIONS: Pre-malignant and malignant endometrial polyps are more common in the subjects with the larger diameters and the thicker endometrium. All polyps should be under complete resection by hysteroscopy and through pathology examination. PMID- 27256446 TI - Adaptive specialization in position encoding while learning to read. AB - The present experiments focused on how orthographic processing develops during reading acquisition. Specifically, a large, cross-sectional sample of children from grade 2 to grade 4 was exposed to pairs of words, pseudowords, digit strings, and pseudo-letter (Armenian) strings while their sensitivity to transpositions (T) and substitutions (S) of internal characters was investigated in a perceptual matching task. The results showed that the development of identity and position decoding diverged between the four stimulus categories. Most importantly, sensitivity improved with longer exposure to formal education and higher reading level to both S and T pairs for digit strings, but only to S pairs for words and pseudowords. The results were successfully reproduced in two small independent samples. We propose a general framework, the Adaptive Specialization Hypothesis, to accommodate the results. According to this hypothesis, the transposed-letter effect is not a hard-wired feature of the orthographic processing system but an adaptive response of the developing orthographic system to the constraints of lexical access in several orthographies. PMID- 27256447 TI - Importance of Metabolic Memory in the Development of Vascular Complications in Diabetic Patients. PMID- 27256448 TI - Developing a Checklist: Consensus Via a Modified Delphi Technique. AB - OBJECTIVE: To create a universal checklist of key preparatory steps to aid anesthesiologists in patient separation from cardiopulmonary bypass. DESIGN: Multistep, iterative survey with statistically guided refinement of survey items using a modified Delphi technique. SETTING: Internet-based surveys. PARTICIPANTS: Ninety active members of the Society of Cardiovascular Anesthesiologists volunteered to participate, including geographically distributed private practice and academic physicians. INTERVENTIONS: A series of checklist items was created and distributed to 90 anesthesiologists, who assessed each item's importance in preparing for patient separation from cardiopulmonary bypass and added, deleted, or modified any items as they saw fit. Items meeting a threshold of greater than 90% group acceptance were carried forward to a second survey. These items then were evaluated using a 5-point Likert scale to grade relative importance and then compared with the group's responses, creating a third survey with refined checklist items. The results then were used to generate a final survey based on each item achieving certain predefined statistical criteria, which then were scored again by the participants, generating a final checklist via statistically guided consensus. MEASUREMENTS AND MAIN RESULTS: An initial checklist containing 28 possible items was proposed to the participants. After the iterative process was completed, a final checklist of 10 items deemed essential to prepare for bypass separation was created. CONCLUSIONS: A checklist to aid in bypass separation was created with key steps derived from a statistically driven Delphi process. This technique of iterative consensus building may be useful in developing additional safety checklists. PMID- 27256451 TI - Concerns that animal testing continues without scientific justification. PMID- 27256449 TI - The gut microbiome in human immunodeficiency virus infection. AB - HIV/AIDS causes severe dysfunction of the immune system through CD4+ T cell depletion, leading to dysregulation of both the adaptive and innate immune arms. A primary target for viral infection is the gastrointestinal tract, which is a reservoir of CD4+ T cells. In addition to being a major immune hub, the human gastrointestinal tract harbors trillions of commensal microorganisms, the microbiota, which have recently been shown to play critical roles in health. Alterations in the composition and function of microbiota have been implicated in a variety of 'multi-factorial' disorders, including infectious, autoimmune, metabolic, and neoplastic disorders. It is widely accepted that, in addition to its direct role in altering the gastrointestinal CD4+ T cell compartment, HIV infection is characterized by gut microbiota compositional and functional changes. Herein, we review such alterations and discuss their potential local and systemic effects on the HIV-positive host, as well as potential roles of novel microbiota-targeting treatments in modulating HIV progression and associated adverse systemic manifestations. PMID- 27256452 TI - Stakeholder views on the creation and use of genetically-engineered animals in research. AB - This interview-based study examined the diversity of views relating to the creation and use of genetically-engineered (GE) animals in biomedical science. Twenty Canadian participants (eight researchers, five research technicians and seven members of the public) took part in the interviews, in which four main themes were discussed: a) how participants felt about the genetic engineering of animals as a practice; b) governance of the creation and use of GE animals in research, and whether current guidelines are sufficient; c) the Three Rs (Replacement, Reduction, Refinement) and how they are applied during the creation and use of GE animals in research; and d) whether public opinion should play a greater role in the creation and use of GE animals. Most of the participants felt that the creation and use of GE animals for biomedical research purposes (as opposed to food purposes) is acceptable, provided that tangible human health benefits are gained. However, obstacles to Three Rs implementation were identified, and the participants agreed that more effort should be placed on engaging the public on the use of GE animals in research. PMID- 27256450 TI - A novel set-up for the ex vivo analysis of mechanical properties of mouse aortic segments stretched at physiological pressure and frequency. AB - KEY POINTS: Cyclic stretch is known to alter intracellular pathways involved in vessel tone regulation. We developed a novel set-up that allows straightforward characterization of the biomechanical properties of the mouse aorta while stretched at a physiological heart rate (600 beats min-1 ). Active vessel tone was shown to have surprisingly large effects on isobaric stiffness. The effect of structural vessel wall alterations was confirmed using a genetic mouse model. This set-up will contribute to a better understanding of how active vessel wall components and mechanical stimuli such as stretch frequency and amplitude regulate aortic mechanics. ABSTRACT: Cyclic stretch is a major contributor to vascular function. However, isolated mouse aortas are frequently studied at low stretch frequency or even in isometric conditions. Pacing experiments in rodents and humans show that arterial compliance is stretch frequency dependent. The Rodent Oscillatory Tension Set-up to study Arterial Compliance is an in-house developed organ bath set-up that clamps aortic segments to imposed preloads at physiological rates up to 600 beats min-1 . The technique enables us to derive pressure-diameter loops and assess biomechanical properties of the segment. To validate the applicability of this set-up we aimed to confirm the effects of distension pressure and vascular smooth muscle tone on arterial stiffness. At physiological stretch frequency (10 Hz), the Peterson modulus (EP ; 293 (10) mmHg) for wild-type mouse aorta increased 22% upon a rise in pressure from 80-120 mmHg to 100-140 mmHg, while, at normal pressure, EP increased 80% upon maximal contraction of the vascular smooth muscle cells. We further validated the method using a mouse model with a mutation in the fibrillin-1 gene and an endothelial nitric oxide synthase knock-out model. Both models are known to have increased arterial stiffness, and this was confirmed using the set-up. To our knowledge, this is the first set-up that facilitates the study of biomechanical properties of mouse aortic segments at physiological stretch frequency and pressure. We believe that this set-up can contribute to a better understanding of how cyclic stretch frequency, amplitude and active vessel wall components influence arterial stiffening. PMID- 27256453 TI - Evaluation of an in vitro cell culture assay for the potency assessment of recombinant human erythropoietin. AB - Recombinant human erythropoietin is a sialoglycoprotein that stimulates erythropoiesis. To assess potency of human erythropoietin produced by recombinant technology, we investigated an in vitro TF-1 cell proliferation assay, which was applied in conjunction with a reversed-phase liquid chromatography method for the determination of the content of sialic acids. The results obtained, which were higher than 126.8ng/MUg, were compared with those obtained with the in vivo normocythaemic mouse bioassay. The in vitro assay resulted in a non-significant lower mean difference of the estimated potencies (0.61% +/- 0.026, p > 0.05). The use of this combination of methods represents an advance toward the establishment of alternative in vitro approaches, in the context of the Three Rs, for the potency assessment of biotechnology-derived medicines. PMID- 27256454 TI - The use of a decision tree based on the rabies diagnosis scenario, to assist the implementation of alternatives to laboratory animals. AB - Brazilian federal legislation makes the use of alternatives mandatory, when there are validated methods to replace the use of laboratory animals. The objective of this paper is to introduce a novel decision tree (DT)-based approach, which can be used to assist the replacement of laboratory animal procedures in Brazil. This project is based on a previous analysis of the rabies diagnosis scenario, in which we identified certain barriers that hinder replacement, such as: a) the perceived higher costs of alternative methods; b) the availability of staff qualified in these methods; c) resistance to change by laboratory staff; d) regulatory obstacles, including incompatibilities between the Federal Environmental Crimes Act and specific norms and working practices relating to the use of laboratory animals; and e) the lack of government incentives. The DT represents a highly promising means to overcome these reported barriers to the replacement of laboratory animal use in Brazil. It provides guidance to address the main obstacles, and, followed step-by-step, would lead to the implementation of validated alternative methods (VAMs), or their development when such alternatives do not exist. The DT appears suitable for application to laboratory animal use scenarios where alternative methods already exist, such as in the case of rabies diagnosis, and could contribute to increase compliance with the Three Rs principles in science and with the current legal requirements in Brazil. PMID- 27256456 TI - Transparency and public involvement in animal research. AB - To be legitimate, research needs to be ethical, methodologically sound, of sufficient value to justify public expenditure and be transparent. Animal research has always been contested on ethical grounds, but there is now mounting evidence of poor scientific method, and growing doubts about its clinical value. So what of transparency? Here we examine the increasing focus on openness within animal research in the UK, analysing recent developments within the Home Office and within the main group representing the interests of the sector, Understanding Animal Research. We argue that, while important steps are being taken toward greater transparency, the legitimacy of animal research continues to be undermined by selective openness. We propose that openness could be increased through public involvement, and that this would bring about much needed improvements in animal research, as it has done in clinical research. PMID- 27256455 TI - Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use. AB - The Family Smoking Prevention and Tobacco Control Act of 2009 established the Food and Drug Administration Center for Tobacco Products (FDA-CTP), and gave it regulatory authority over the marketing, manufacture and distribution of tobacco products, including those termed 'modified risk'. On 8-10 December 2014, IIVS organised a workshop conference, entitled Assessment of In Vitro COPD Models for Tobacco Regulatory Science, to bring together stakeholders representing regulatory agencies, academia, industry and animal protection, to address the research priorities articulated by the FDA-CTP. Specific topics were covered to assess the status of current in vitro technologies as they are applied to understanding the adverse pulmonary events resulting from tobacco product exposure, and in particular, the progression of chronic obstructive pulmonary disease (COPD). The four topics covered were: a) Inflammation and Oxidative Stress; b) Ciliary Dysfunction and Ion Transport; c) Goblet Cell Hyperplasia and Mucus Production; and d) Parenchymal/Bronchial Tissue Destruction and Remodelling. The 2.5 day workshop included 18 expert speakers, plus poster sessions, networking and breakout sessions, which identified key findings and provided recommendations to advance the in vitro technologies and assays used to evaluate tobacco-induced disease etiologies. The workshop summary was reported at the 2015 Society of Toxicology Annual Meeting, and the recommendations led to an IIVS-organised technical workshop in June 2015, entitled Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays, to assess these assays and to conduct a proof-of-principle multi-laboratory exercise to determine their suitability for standardisation. Here, we report on the proceedings, recommendations and outcomes of the December 2014 workshop, including paths forward to continue the development of non-animal methods to evaluate tissue responses that model the disease processes that may lead to COPD, a major cause of mortality worldwide. PMID- 27256457 TI - Acceptance, Usability and Health Applications of Virtual Worlds by Older Adults: A Feasibility Study. AB - BACKGROUND: Virtual worlds allow users to communicate and interact across various environments, scenarios, and platforms. Virtual worlds present opportunities in health care to reduce the burden of illness and disability by supporting education, rehabilitation, self-management, and social networking. The application of virtual worlds to older adults who bear the burden and cost of health conditions associated with age has not been evaluated. OBJECTIVE: The aim of this study is to explore the usability, ease of use, and enjoyment of a virtual world by older adults, the types of virtual world activities that older adults may engage in, and the perceptions of older adults regarding the application of virtual worlds in health care. METHODS: This quasi-experimental pre-post design research was guided by the Technology Acceptance Model (TAM). Participants were recruited from a Lifelong Learning Institute (LLI) program at Nova Southeastern University. Participants attended four training sessions over a 5-week period in the Second Life (SL) virtual world. Subjects were surveyed before and after the training on perceived ease of use, attitudes towards technology, behavioral intention to use the system, facilitating conditions, effort expectancy, and self-efficacy. RESULTS: Older adults (N=19) completed the informed consent and attended the first training session, and 11 participants (58%, 11/19) completed the full training and the post survey. Completers (82%, 9/11) were more likely than non-completers (37%, 3/8) to consider themselves technologically savvy (P=.048), and to express confidence in being able to use the virtual world (100%, 11/11 vs 37%, 3/8; P=.002). All completers (100%, 11/11) perceived that SL has application in health behaviors and disease and reducing social isolation among people who are homebound. Of the completers, 10 (91%, 10/11) responded that they enjoyed learning how to use SL. Completers suggested that future trainings include more assistants and smaller groups. CONCLUSIONS: This pilot study suggests that virtual worlds can be both a feasible and an applicable method to promote health among some seniors. Future research on virtual worlds with older populations should consider using state-of-the art technology including large monitors, providing a minimum of one trainer for every two to three participants, and distributing a comprehensive training manual at the start of the training to support organization and recall. PMID- 27256458 TI - Positive impact on heat loss and patient experience of preheated skin disinfection: a randomised controlled trial. AB - AIMS AND OBJECTIVES: The aim of this study was to compare the effect of preheated (36 degrees C) and room-temperature (20 degrees C) skin disinfectant solution on skin temperature and patients' experience of the skin disinfection process. BACKGROUND: To prevent surgical site infections, it is important to disinfect skin prior to invasive surgery. In clinical practice, conscious patients often comment on the coldness of the preoperative skin disinfection solution. Evidence is lacking, as to whether preheated skin disinfectant has any positive effects during preoperative skin disinfection. DESIGN: Randomised controlled trial. METHODS: A total of 220 patients undergoing pacemaker, implantable cardioverter defibrillator, or cardiac resynchronisation therapy under local anaesthesia were included and randomly allocated to preheated or room-temperature skin disinfection. Skin temperature was assessed before and after skin disinfection at the planned incision site; in addition, three study-specific questions were used to assess how patients experienced the temperature. RESULTS: Patients experienced the skin disinfection process with preheated disinfectant as significantly more pleasant. They felt less cold and reported increased satisfaction with the temperature of the solution compared to patients who were disinfected with room temperature solution. Skin disinfection with preheated solution also yielded a significantly higher mean skin temperature compared to room-temperature solution. CONCLUSIONS: Preoperative skin disinfection with preheated disinfectant may prevent heat loss and contributes to a more pleasant experience for patients. RELEVANCE TO CLINICAL PRACTICE: Skin disinfection with preheated skin disinfectant is an easy and inexpensive nursing intervention that has a positive impact on heat loss and on patients' experience of the disinfection process. PMID- 27256460 TI - Arsenic poisoning and Mees' lines. PMID- 27256459 TI - Investigation of the expression of irisin and some cachectic factors in mice with experimentally induced gastric cancer. AB - BACKGROUND: The purpose of this study was to determine whether irisin is secreted by gastric tumor cells experimentally induced in mice, and also if it has any effect on cancer cachexia. DESIGN AND METHODS: 12 out of 60 BALB/c mice were used as a control group, while N-nitroso-N-methylurea (MNU) was administered orally to the remaining 48. After 150 days, the surviving mice were sacrificed by decapitation, blood and stomach, skeletal muscle, brown and white adipose tissue specimens were collected. Following histopathological evaluation of the stomach tissues, it was decided to create four groups, one control group and three consisting of mice administered MNU, no cancer, pre-cancer and cancer. Gene expression analyses of fibronectin type III domain containing protein 5 (FNDC5) and some cachexia-related proteins were performed in tissue samples, while levels of irisin, and various inflammatory and tumor markers together with cachectic factors were determined in serum samples. RESULTS: The levels of inflammatory, tumor markers and cachectic factors in serum samples were significantly higher in the cancer group compared with the control group. No expression of FNDC5 or zinc alpha-2 glycoprotein, a cachectic factor, was observed in gastric tissues from the control and MNU groups, whereas significantly increased FNDC5 expression was determined in the both white and brown adipose tissues from the cancer group. CONCLUSION: Increased FNDC5 expression in white and brown adipose tissues may have a cachectic effect in mice with induced cancer. However, it is not possible to explain the mechanism of the relationship between irisin and gastric cancer development on the basis of the results of this study. PMID- 27256461 TI - Response to the letter by PAJ de Leeuw, GMMJ Kerkhoffs. PMID- 27256462 TI - Defects in early cell recruitment contribute to the increased susceptibility to respiratory Klebsiella pneumoniae infection in diabetic mice. AB - Diabetes is associated with increased susceptibility to Klebsiella pneumoniae and poor prognosis with infection. We demonstrate accelerated mortality in mice with streptozotocin-induced diabetes following tracheal instillation of K. pneumoniae. Diabetic mice recruited fewer granulocytes to the alveolar airspace and had reduced early production of CXCL1, CXCL2, IL-1beta and TNF-alpha following tracheal instillation of K. pneumoniae-lipopolysaccharide. Additionally, TLR2 and TIRAP expression following K. pneumoniae-lipopolysaccharide exposure was decreased in hyperglycemic mice. These findings indicate that impaired innate sensing and failure to rapidly recruit granulocytes to the site of infection is a mechanism for diabetic susceptibility to respiratory K. pneumoniae infection. PMID- 27256463 TI - TLR2 modulates gut colonization and dissemination of Candida albicans in a murine model. AB - Invasive candidiasis often arises from translocation of endogenous yeasts from the gastrointestinal tract to the bloodstream. Here we describe that both wild type and TLR2-/- mice strains, orally administered with Candida albicans yeasts, display similar sustained high level of gut colonization when oral antibacterial treatment is present, while removal of antibiotic treatment causes a progressive clearance of yeasts in control but not in TLR2-/- mice. Fungal invasion of internal organs, following immunosuppression of colonized mice, was increased in TLR2-/- mice. These results point out to a role of TLR2 in gut protection against colonization and endogenous invasion by C. albicans. PMID- 27256464 TI - Rab32/38 and the xenophagic restriction of intracellular bacteria replication. AB - Rab GTPases' subversion by intracellular pathogens during infection has been extensively documented. Recent findings have implicated a key intracellular bacterial restriction/containment function for Rab32/38 in Salmonella species in macrophages and Listeria monocytogenes in dendritic cells. Rab32/38 aids the phagolysosome maturation, and mediates a parallel xenophagy mechanism by engaging prohibitins. PMID- 27256466 TI - Clinical and genetic profile of catecholaminergic polymorphic ventricular tachycardia in Hong Kong Chinese children. AB - OBJECTIVE: To report our experience in the management of catecholaminergic polymorphic ventricular tachycardia in Hong Kong Chinese children. METHODS: This case series study was conducted in a tertiary paediatric cardiology centre in Hong Kong. All paediatric patients diagnosed at our centre with catecholaminergic polymorphic ventricular tachycardia from January 2008 to October 2014 were included. RESULTS: Ten patients (five females and five males) were identified. The mean age at presentation and at diagnosis were 11.0 (standard deviation, 2.9) years and 12.5 (2.8) years, respectively. The mean delay time from first presentation to diagnosis was 1.5 (standard deviation, 1.3) years. They presented with recurrent syncope and six patients had a history of aborted cardiac arrest. Four patients were initially misdiagnosed to have epilepsy. Catecholaminergic polymorphic ventricular tachycardia was diagnosed by electrocardiogram at cardiac arrest (n=2), or provocation test, either by catecholamine infusion test (n=6) or exercise test (n=2). Mutations of the RyR2 gene were confirmed in six patients. Nine patients were commenced on beta-blockers after diagnosis. Despite medications, three patients developed aborted or resuscitated cardiac arrest (n=2) and syncope (n=1). Left cardiac sympathetic denervation was performed in five patients and an implantable cardioverter defibrillator was implanted in another. There was no mortality during follow-up. CONCLUSIONS: Catecholaminergic polymorphic ventricular tachycardia should be considered in children who present with recurrent syncope during exercise or emotional stress. Despite beta-blocker treatment, recurrent ventricular arrhythmias occur and may result in cardiac arrest. PMID- 27256465 TI - TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis. AB - Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis. PMID- 27256467 TI - Managing malignant pleural effusion with an indwelling pleural catheter: factors associated with spontaneous pleurodesis. AB - INTRODUCTION: Malignant pleural effusion can be recurrent despite active anti cancer treatment. Significant malignant pleural effusion leads to debilitating dyspnoea and worsening quality of life in patients with advanced cancer. An indwelling pleural catheter offers a novel means to manage recurrent malignant pleural effusion and may remove the need for repeated thoracocentesis. Spontaneous pleurodesis is another unique advantage of indwelling pleural catheter placement but the factors associated with its occurrence are not clearly established. The aims of this study were to explore the safety of an indwelling pleural catheter in the management of symptomatic recurrent malignant pleural effusion, and to identify the factors associated with spontaneous pleurodesis. METHODS: This case series with internal comparisons was conducted in the Division of Respiratory Medicine, Department of Medicine, Queen Mary Hospital, Hong Kong. All patients who underwent insertion of an indwelling pleural catheter from the initiation of such service from January 2010 to December 2014 were included for data analysis. Patients were monitored until December 2014, with the last catheter inserted in July 2014. RESULTS: Between 2010 and 2014, a total of 23 indwelling pleural catheters were inserted in 22 consecutive patients with malignant pleural effusion, including 15 (65.2%) cases with malignant pleural effusion as a result of metastatic lung cancer. Ten (43.5%) cases achieved minimal output according to defined criteria, in five of whom the pleural catheter was removed without subsequent re-accumulation of effusion (ie spontaneous pleurodesis). Factors associated with minimal output were the absence of trapped lung (P=0.036), shorter time from first appearance of malignant pleural effusion to catheter insertion (P=0.017), and longer time from catheter insertion till patient's death or end of study (P=0.007). CONCLUSIONS: An indwelling pleural catheter provides a safe means to manage symptomatic malignant pleural effusion. Potential clinical factors associated with minimal output were identified along with the occurrence of spontaneous pleurodesis, which is a unique advantage offered by indwelling pleural catheter. PMID- 27256468 TI - Validity and reliability of the Chinese version of the Insulin Treatment Appraisal Scale among primary care patients in Hong Kong. AB - INTRODUCTION: Patients with diabetes mellitus often delay insulin initiation and titration due to psychological factors. This phenomenon is known as 'psychological insulin resistance'. Tools that identify psychological insulin resistance are valuable for detecting its causes and can lead to appropriate counselling. The Insulin Treatment Appraisal Scale was initially developed for western populations and has been translated and validated to measure psychological insulin resistance in Taiwan (Chinese version of the Insulin Treatment Appraisal Scale, C-ITAS). The current study examined the prevalence of psychological insulin resistance and the validity of the C-ITAS in a local population. METHODS: This cross-sectional study involved 360 patients with diabetes mellitus from a government-funded general out-patient clinic who completed the C-ITAS questionnaire. The total C-ITAS score was compared for patients with psychological insulin resistance and those without, and the internal consistency and test-retest reliability of the C-ITAS were calculated. An exploratory factor analysis was used to identify factors within the C-ITAS. RESULTS: The prevalence of psychological insulin resistance was 44.9%. The internal consistency of the scale was high (Cronbach's alpha=0.78). The test retest reliability was positive with all C-ITAS questions (0.294-0.725). The mean C-ITAS score was significantly higher among patients with psychological insulin resistance than those without (42.42 vs 35.78; P<0.001). The exploratory factor analysis, however, failed to identify the two clear factors identified in the original validation study. CONCLUSIONS: The C-ITAS appears to be a feasible and potentially useful tool for identifying psychological insulin resistance, but additional validation or translation is required before it can be widely used clinically. PMID- 27256469 TI - Correlation of thermal deficit with clinical parameters and functional status in patients with unilateral lumbosacral radiculopathy. AB - INTRODUCTION: Lumbosacral radiculopathy is a pathological process that refers to the dysfunction of one or more spinal nerve roots in the lumbosacral region of the spine. Some studies have shown that infrared thermography can estimate the severity of the clinical manifestation of unilateral lumbosacral radiculopathy. This study aimed to examine the correlation of the regional thermal deficit of the affected lower extremity with pain intensity, mobility of the lumbar spine, and functional status in patients with unilateral lumbosacral radiculopathy. METHODS: This cross-sectional study was conducted at the Clinic for Physical Medicine and Rehabilitation of the Clinical Center Nis, Serbia. A total of 69 patients with unilateral lumbosacral radiculopathy of discogenic origin were recruited, with the following clinical parameters evaluated: (1) pain intensity by using a visual analogue scale, separately at rest and during active movement; (2) mobility of the lumbar spine by Schober test and the fingertip-to-floor test; and (3) functional status by the Oswestry Disability Index. Temperature differences between the symmetrical regions of the lower extremities were detected by infrared thermography. A quantitative analysis of thermograms determined the regions of interest with maximum thermal deficit. Correlation of maximum thermal deficit with each tested parameter was then determined. RESULTS: A significant and strong positive correlation was found between the regional thermal deficit and pain intensity at rest, as well as pain during active movements (rVAS - rest=0.887, rVAS - activity=0.890; P<0.001). The regional thermal deficit significantly and strongly correlated with the Oswestry Disability Index score and limited mobility of the lumbar spine (P<0.001). CONCLUSIONS: In patients with unilateral lumbosacral radiculopathy, the values of regional thermal deficit of the affected lower extremity are correlated with pain intensity, mobility of the lumbar spine, and functional status of the patient. PMID- 27256470 TI - Update on PET/CT colonography in the diagnosis of colorectal cancer. PMID- 27256471 TI - Temporal trend in the reported birth prevalence of cleft lip and/or cleft palate in Brazil, 2000 to 2013. AB - BACKGROUND: The birth prevalence of cleft lip with or without cleft palate (CL/P) in Brazil increased between the years from 1975 to 1994 but has not been evaluated for temporal trend since then. METHODS: We used data from the Brazilian National Health Information System for the years 2000 through 2013. We calculated the reported CL/P birth prevalence each year per 10,000 live births and estimated the average increase in reported prevalence per year (and 95% confidence interval [CI]) by fitting a negative binomial regression model. We also estimated the temporal trend in each of the five Brazilian regions for this time period. RESULTS: The overall reported birth prevalence was 4.85 (95% CI, 4.78-4.91) per 10,000 live births. The reported birth prevalence of CL/P increased over this time period, from 3.94 (95% CI, 3.73-4.17) per 10,000 in 2000 to 5.46 (95% CI, 5.20-5.74) per 10,000 in 2013. The temporal trend differed for different Brazilian geographic regions, being confined primarily to the Northeast (4.7% per year; 95% CI, 4.0%-5.5%), North (3.3% per year; 95% CI, 1.8%-4.7%), and Central (2.9% per year; 95% CI, 0.9%-4.9%) regions. CONCLUSION: In recent years, there appears to be an upward trend in the reported prevalence of CL/P in Brazil, confined to the less developed regions of the country. The increase likely reflects improved surveillance; whether it also reflects etiologic differences is unknown. Birth Defects Research (Part A) 106:789-792, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27256472 TI - Embolic strokes of undetermined source: Prevalence and patient features in the ESUS Global Registry. AB - BACKGROUND: Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). AIMS: We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. METHODS: Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. RESULTS: Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p <= 0.001). Excluding patients with atrial fibrillation (n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years (p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2 8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. CONCLUSIONS: This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions. PMID- 27256473 TI - Contrast-enhanced ultrasonography for detecting histological carotid plaque rupture: Quantitative analysis of ulcer. AB - BACKGROUND: Few studies have evaluated the distinct ability of contrast-enhanced ultrasonography for detecting carotid plaque rupture versus histological observations. AIMS: The aim of this study was to quantitatively assess the ability of contrast-enhanced ultrasonography to detect plaque rupture compared to ultrasonographic and histological images in terms of geometric accordance. METHODS: Carotid plaque morphology was classified as "smooth," "irregular," or "ulcerated" on 45 conventional ultrasonography and contrast-enhanced ultrasonography images from consecutive patients undergoing endarterectomy, and 55 regions of interests were captured on contrast-enhanced ultrasonography. A comparative study with a receiver operating characteristic analysis was performed using histological findings for reference. RESULTS: Contrast-enhanced ultrasonography exhibited a higher percentage of "ulcerated" findings in patients with plaque rupture compared to conventional ultrasonography (P = 0.002) as well as an association with thrombus formation (P = 0.048) and fibrous cap disruption (P < 0.0001). On contrast-enhanced ultrasonography, "ulcerated" were significantly more likely than "smooth" findings when the fibrous cap was disrupted (odds ratio (OR), 41.5). The receiver operating characteristic areas under the curve for the orifice, depth, and width of the concavities on contrast enhanced ultrasonography were significantly greater than 0.5, while their optimal cut-off values were 1.40 mm, 1.30 mm, and 1.88 mm, respectively. When one of these variables was greater than the optimal cut-off value, the sensitivity, negative hit rate, and odds ratio for detecting fibrous cap disruption were 91.3%, 91.6%, and 23.1, respectively. CONCLUSIONS: In our study, contrast enhanced ultrasonography has high sensitivity for identifying histological plaque rupture, and the measurement of concavity on contrast-enhanced ultrasonography may enable the accurate detection of fibrous cap disruption. PMID- 27256474 TI - Endarterectomy vs. stenting vs. medical therapy. AB - In recent trials, after deducting the risks in the 30-day periprocedural period, the long-term risk of stroke or death was similar with carotid stenting (CAS) and endarterectomy (CEA) for asymptomatic carotid stenosis (ACS) - approximately 0.5% per year. These findings may exacerbate the problem of inappropriate routine intervention in ACS, being justified on the basis of an invalid comparison of the risks in the medical arms of clinical trials conducted decades ago (~ 2% per year) to the risks in modern trials of CAS vs. CEA with no medical arm. Intervention is regarded as justified if it can be carried out with a risk below 3%. The annual risk of ipsilateral stroke or death in ACS with intensive medical therapy is now ~ 0.5% - similar to the long-term risk after the periprocedural period in recent trials of intervention. However, periprocedural risk was ~ 3% for CAS and 1.7% for CEA. Thus with modern CAS and CEA, the risk remains much higher than with modern medical therapy, even with careful vetting of the surgeons and interventionalists. In real world practice, documented in registries, the risks are much higher. National differences - 90% of carotid intervention for ACS in the US vs. 0% in Denmark - bring into question the advisability and ethics of routine intervention. A moratorium on routine intervention for ACS should be respected except in ongoing randomized trials comparing CAS, CEA and modern intensive medical therapy. Patients with high-risk ACS can be identified for appropriate intervention. PMID- 27256475 TI - Clinical management and hospital outcomes of acute coronary syndrome patients in Mexico: The Third National Registry of Acute Coronary Syndromes (RENASICA III). AB - OBJECTIVE: To describe current management and clinical outcomes in patients hospitalized with an acute coronary syndrome (ACS) in Mexico. METHODS: RENASICA III was a prospective multicenter registry of consecutive patients hospitalized with an ACS. Patients had objective evidence of ischemic heart disease; those with type II infarction or secondary ischemic were excluded. Study design conformed to current quality recommendations. RESULTS: A total of 123 investigators at 29 tertiary and 44 community hospitals enrolled 8296 patients with an ACS (4038 with non-ST-elevation myocardial infarction/unstable angina [NSTEMI/UA], 4258 with ST-elevation myocardial infarction [STEMI]). The majority were younger (62+/-12years) and 76.0% were male. On admission 80.5% had ischemic chest pain lasting >20min and clinical stability. Left ventricular dysfunction was more frequent in NSTEMI/UA than in those with STEMI (30.0% vs. 10.7%, p<0.0001). In STEMI 37.6% received thrombolysis and 15.0% primary PCI. PCI was performed in 39.6% of NSTEMI/UA (early strategy in 10.8%, urgent strategy in 3.0%). Overall hospital death rate was 6.4% (8.7% in STEMI vs. 3.9% in NSTEMI/UA, p<0.001). The strongest independent predictors of hospital mortality were cardiogenic shock (odds ratio 22.4, 95% confidence interval 18.3-27.3) and ventricular fibrillation (odds ratio 12.5, 95% confidence interval 9.3-16.7). CONCLUSION: The results from RENASICA III establish the urgent need to develop large-scale regional programs to improve adherence to guideline recommendations in ACS, including rates of pharmacological thrombolysis and increasing the ratio of PCI to thrombolysis. PMID- 27256477 TI - Use of surrogate end points in healthcare policy: a proposal for adoption of a validation framework. PMID- 27256478 TI - A polysaccharide from the stems of Rubus amabilis Focke and its immunological enhancement activity. AB - A water-soluble polysaccharide (named RAP) was newly isolated from the stems of Rubus amabilis. Structural confirmation of the polysaccharide was provided by hydrolysis, periodate oxidation, Smith degradation, and methylation analysis, combined with nuclear magnetic resonance (NMR), capillary electrophoresis (CE), infrared spectroscopy (IR), and gas chromatography-mass spectra (GC-MS). In vitro immunological enhancement activity was characterized using the proliferative activity of spleen lymphocytes and phagocytic activity of peritoneal macrophages in mice. The polysaccharide was mainly composed of xylose, arabinose, glucose, rhamnose, galactose, mannose, glucuronic acid, and galactocuronic acid in the molar ratio of 1.0:6.9:0.8:1.1:6.9:0.3:0.5:3.3, with the average molecular weight of 26.2 kDa. The linkage types of netural monosaccharides were as follows: the arabinose was ->2) Ara (1-> and galactose were Gal (1->, ->3) Gal (1->, ->3,6) Gal (1->, ->2,3,6) Gal (1-> and ->2,3,6) Galf (1->. Xyl (1->, ->6) Glc (1->, ->2) Glc (1->, ->3) Rha (1->, Rha (1-> and Man (1-> were also found in the structure. RAP-B-2 could improve the proliferative activity of spleen T cells and B cells and boost phagocytic activity of peritoneal macrophages at the concentration of 50 MUg/ml (p < 0.05, p < 0.01). PMID- 27256479 TI - [An unusual variant of a rare sacro-coccygeal tumor]. PMID- 27256480 TI - Identifying health service barriers in the management of co-morbid diabetes and chronic kidney disease in primary care: a mixed-methods exploration. AB - BACKGROUND: Co-morbid diabetes and chronic kidney disease (CKD) are common in primary care but health care can be suboptimal. OBJECTIVE: In this multi-centre mixed-methods study, we investigated GPs' perspectives on health service barriers in managing diabetes and CKD as an initial step towards health care improvement. METHODS: Four focus groups were conducted among GPs in Australia's two largest cities. Transcripts underwent content analysis to inform development of a survey exploring health service barriers. This survey was then emailed/mailed to 840 GPs. Statistical analyses were performed using STATA v2.1. RESULTS: Responses were received from 13.7% of GPs (n = 115), mean (+/-SD) age 55.3 (10.1) years and mean duration of practice 26.6 (10.6). The majority (88.4%) reported wanting to manage diabetes and CKD in primary care with specialist assistance. However, 34.8% were unclear about the definition of CKD with 73.2% wanting more education. Access to specialist services was problematic with 39.3% and 28.2% reporting the process of referring patients to diabetes or CKD services, respectively, as hard. Coordination of care was also a problem with 35.6% unclear about each health care provider's role, 50.5% believing patients faced difficulties due to poor coordination across providers and 51.6% reporting duplication of tests. CONCLUSIONS: GPs expressed a clear interest in being the principal health care providers for patients with co-morbid diabetes and CKD. Supporting GPs and health care improvement focusing on overcoming reported barriers such as inadequate knowledge about CKD, access to specialist services and coordination of care may improve outcomes for people with co-morbid diabetes and CKD. PMID- 27256481 TI - Effects of l-carnitine and/or maize distillers dried grains with solubles in diets of gestating and lactating sows on the intestinal barrier functions of their offspring. AB - The objective of this study was to investigate the effects of l-carnitine and/or maize distillers dried grains with solubles (DDGS) in diets of gestating and lactating sows on the intestinal barrier functions of their offspring. The experiment was designed as a 2*2 factorial with two dietary treatments (soyabean meal v. DDGS) and two l-carnitine levels (0 v. 100 mg/kg in gestating diets and 0 v. 200 mg/kg in lactating diets). Sows (Landrace*Large White) with an average parity of 4.2 with similar body weight were randomly assigned to four groups of thirty each. Dietary supplementation with l-carnitine increased the total superoxide dismutase activity but decreased the concentration of malondialdehyde of the jejunal mucosa in newborn piglets and weaning piglets on day 21. Dietary supplementation with l-carnitine decreased the concentrations of IL-1beta, IL-12 and TNF-alpha in the jejunal mucosa of newborn piglets and decreased the concentrations of IL-6 and TNF-alpha in the jejunal mucosa of weaning piglets on day 21. There was an interaction between dietary treatment and l-carnitine on the bacterial numbers of total eubacteria in the digesta of caecum in weaning piglets on day 21. Bacterial numbers of total eubacteria in weaning piglets on day 21 were significantly increased by l-carnitine only in soyabean meal diet, but there was no significant effect of l-carnitine in DDGS-based diet. Dietary supplementation with l-carnitine increased the bacterial numbers of Lactobacillus spp. and bifidobacteria spp. in the digesta of caecum in weaning piglets on day 21. Dietary supplementation with l-carnitine in sows affected the expression of tight junction proteins (claudin 1, zonula occludens-1 (ZO-1) and occludin) in the jejunal mucosa of their offspring by increasing the expression of ZO-1 mRNA in the jejunal mucosa of newborn piglets, and by increasing the expression of ZO 1 and occludin mRNA in the jejunal mucosa of weaning piglets on day 21. In conclusion, dietary supplementation with l-carnitine in gestating and lactating sows had positive effects on intestinal barrier functions of newborn piglets and weaning piglets on day 21, but it did not have effects on intestinal barrier functions of growing-finishing pigs in the filial generation. There were no effects of dietary treatment of sows on intestinal barrier functions in their offspring. PMID- 27256476 TI - Targeting adipose tissue in the treatment of obesity-associated diabetes. AB - Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis. PMID- 27256482 TI - Preimplantation genetic screening 2.0: the theory. AB - During the last few years a new generation of preimplantation genetic screening (PGS) has been introduced. In this paper, an overview of the different aspects of this so-called PGS 2.0 with respect to the why (what are the indications), the when (which developmental stage, i.e. which material should be studied) and the how (which molecular technique should be used) is given. With respect to the aims it is clear that PGS 2.0 can be used for a variety of indications. However, the beneficial effect of PGS 2.0 has not been proved yet in RCTs. It is clear that cleavage stage is not the optimal stage for biopsy. Almost all advocates of PGS 2.0 prefer trophectoderm biopsy. There are many new methods that allow the study of complete aneuploidy with respect to one or more of the 24 chromosomes. Because of the improved vitrification methods, selection of fresh embryos for transfer is more and more often replaced by frozen embryo transfer. The main goal of PGS has always been the improvement of IVF success. However, success is defined by different authors in many different ways. This makes it very difficult to compare the outcomes of different studies. In conclusion, the introduction of PGS 2.0 will depend on the success of the new biopsy strategies in combination with the analysis of all 24 chromosomes. It remains to be seen which approach will be the most successful and for which specific groups of patients. PMID- 27256484 TI - How should we test infant handedness? AB - As soon as infants grasp objects, they exhibit some degree of hand preference. Although all studies agree that the number of non-lateralized infants remains high during the first months of life, there is no consensus on the percentage of right- and left-handed infants. Reasons might be the different formulae used to calculate an handedness index, the basis on which handedness categories are distinguished, and the number of trials per session. In this study we aimed to provide a valid method of testing handedness, reliable without being lengthy so as to combine it with other evaluations. We tested 46 infants at 9 and 11 months by giving them 34 trials. We compared the results using 2 of the most used formulae, including the bimanual grasps or not, and considering the first 5, 10, 15, 20, 26, 31, or all 34 trials. The results show that different formulae do not give significantly different results as long as bimanual grasps are included. The number of trials is important: 15 trials are necessary for the reliability of the classification into handedness categories. Giving more trials does not provide substantial additional information. PMID- 27256485 TI - Direct and extended intergenerational contact and young people's attitudes towards older adults. AB - Research suggests that positive intergenerational contact can improve young people's attitudes towards older adults. However, today's age-segregated society may not provide ample opportunities for positive contact between younger and older adults to occur on a regular basis. In three studies, we investigated whether the positive attitudinal outcomes associated with direct contact might also stem from a more indirect form of intergenerational relationship: extended contact. In Study 1 (N = 70), extended contact was associated with more positive attitudes towards older adults even when controlling for direct intergenerational contact (contact frequency and contact quality). In Study 2 (N = 110), the positive effects of direct and extended contact on young people's age-related attitudes were mediated by reductions in intergroup anxiety and ageing anxiety. The mediational effects of intergroup anxiety were replicated in Study 3 (N = 95) and ingroup norms additionally emerged as a mediator of the positive effects of extended contact on young people's attitudes towards older adults. Discussion focuses on the implications for strategies aimed at tackling ageism. PMID- 27256483 TI - The why, the how and the when of PGS 2.0: current practices and expert opinions of fertility specialists, molecular biologists, and embryologists. AB - STUDY QUESTION: We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0? STUDY FINDING: Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS. WHAT IS KNOWN ALREADY: It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage stage but whether mosaicism is no issue at all at the blastocyst stage is currently called into question. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: A questionnaire was developed on the three major aspects of PGS 2.0: the Why, with general questions such as PGS 2.0 indications; the How, specifically on genetic analysis methods; the When, on the ideal method and timing of embryo biopsy. Thirty-five colleagues have been selected to address these questions on the basis of their experience with PGS, and demonstrated by peer-reviewed publications, presentations at meetings and participation in the discussion. The first group of experts who were asked about 'The Why' comprised fertility experts, the second group of molecular biologists were asked about 'The How' and the third group of embryologists were asked about 'The When'. Furthermore, the geographical distribution of the experts has been taken into account. Thirty have filled in the questionnaire as well as actively participated in the redaction of the current paper. MAIN RESULTS AND THE ROLE OF CHANCE: The 30 participants were from Europe (Belgium, Germany, Greece, Italy, Netherlands, Spain, UK) and the USA. Array comparative genome hybridization is the most widely used method amongst the participants, but it is slowly being replaced by massive parallel sequencing. Most participants offering PGS 2.0 to their patients prefer blastocyst biopsy. The high efficiency of vitrification of blastocysts has added a layer of complexity to the discussion, and it is not clear whether PGS in combination with vitrification, PGS alone, or vitrification alone, followed by serial thawing and eSET will be the favoured approach. The opinions range from in favour of the introduction of PGS 2.0 for all IVF patients, over the proposal to use PGS as a tool to rank embryos according to their implantation potential, to scepticism towards PGS pending a positive outcome of robust, reliable and large-scale RCTs in distinct patient groups. LIMITATIONS, REASONS FOR CAUTION: Care was taken to obtain a wide spectrum of views from carefully chosen experts. However, not all invited experts agreed to participate, which explains a lack of geographical coverage in some areas, for example China. This paper is a collation of current practices and opinions, and it was outside the scope of this study to bring a scientific, once-and-for-all solution to the ongoing debate. WIDER IMPLICATIONS OF THE FINDINGS: This paper is unique in that it brings together opinions on PGS 2.0 from all different perspectives and gives an overview of currently applied technologies as well as potential future developments. It will be a useful reference for fertility specialists with an expertise outside reproductive genetics. LARGE SCALE DATA: none. STUDY FUNDING AND COMPETING INTERESTS: No specific funding was obtained to conduct this questionnaire. PMID- 27256486 TI - An evidence-update on the prospective relationship between childhood sedentary behaviour and biomedical health indicators: a systematic review and meta analysis. AB - Evidence for adverse health effects of excessive sedentary behaviour in children is predominantly based on cross-sectional studies, measuring TV viewing as proxy for sedentary behaviour. This systematic review and meta-analysis summarizes the evidence on the prospective relationship between childhood sedentary behaviour and biomedical health indicators, overall and stratified by type of sedentary behaviour (TV viewing, computer use/games, screen time and objective sedentary time). PubMed, EMBASE, PsycINFO and Cochrane were systematically searched till January 2015. Methodological quality of all included studies was scored, and a best evidence synthesis was applied. We included 109 studies of which 19 were of high quality. We found moderate-to-strong evidence for a relationship of overall sedentary time with some anthropometrics (overweight/obesity, weight-for-height), one cardiometabolic biomarker (HDL-cholesterol) and some fitness indicators (fitness, being unfit). For other health indicators, we found no convincing evidence because of inconsistent or non-significant findings. The evidence varied by type of sedentary behaviour. The meta-analysis indicated that each additional baseline hour of TV viewing (beta = 0.01, 95%CI = [-0.002; 0.02]) or computer use (beta = 0.00, 95%CI = [-0.004; 0.01]) per day was not significantly related with BMI at follow-up. We conclude that the evidence for a prospective relationship between childhood sedentary behaviour and biomedical health is in general unconvincing. PMID- 27256487 TI - Treatment of Lung Cancer Patients With Actionable Mutations in the Intensive Care Unit. AB - BACKGROUND: Patients with advanced-stage non-small-cell lung cancer (NSCLC) have high mortality rates in the intensive care unit (ICU). Although the benefit of chemotherapy for hematologic malignancies in the ICU has previously been explored, few data exist regarding the use of targeted therapy for NSCLC in such settings. The primary objective of the present study was to report our experience with the use of targeted therapy in patients with NSCLC in the ICU. MATERIALS AND METHODS: We performed a single-institution, retrospective medical record review. The eligibility criteria included patients with NSCLC with targetable mutations who had received tyrosine kinase inhibitors (TKIs) in the ICU. Cases were identified by queries of our institution's information warehouse database and pharmacy dispensary records from 2010 to 2015. RESULTS: All 9 patients who had received TKIs in the ICU had acute respiratory failure. Three patients were successfully extubated after initiating TKI therapy, although 1 required later tracheostomy. TKI therapy stabilized another patient's refractory disseminated intravascular coagulation. The remaining 5 patients showed no measurable clinical improvement and were transitioned to comfort care. The overall ICU mortality rate was 56%. CONCLUSION: Patients with metastatic NSCLC requiring mechanical ventilation have high mortality rates. Cytotoxic chemotherapy is generally contraindicated for poor performance status patients. However, targeted TKI therapy should be considered, given its proven efficacy and few systemic side effects. We recommend the empiric use of targeted therapy for NSCLC patients with suspected and/or known actionable mutations presenting with multifactorial respiratory failure to the ICU, with aggressive determination of the mutation status if not known. PMID- 27256488 TI - Cross-sectional and prospective impact of reallocating sedentary time to physical activity on children's body composition. AB - BACKGROUND: The amount of time children spend in sedentary behaviours may have adverse health effects. OBJECTIVE: To examine the substitution effects of displacing a fixed duration of sedentary time with physical activity (PA) on children's body composition. METHODS: We included 386 children (197 boys). Outcomes were body mass index, waist circumference, total body fat mass and trunk fat mass assessed by dual-energy X-ray absorptiometry. Sedentary time and PA were measured with accelerometers. Data were analysed by isotemporal analyses estimating the effect of reallocating 15 and 30 min d-1 of sedentary time into light (light physical activity), and moderate-to-vigorous (MVPA) PA on body composition. RESULTS: Reallocating 15 and 30 min d-1 of sedentary time into MVPA was negatively associated with body fatness in cross-sectional analyses. Prospectively, reallocating 30 min of sedentary time into 30 min of MVPA was negatively associated with waist circumference (beta = -1.11, p < 0.05), trunk fat mass (beta = -0.21, p < 0.05), and total body fat mass (beta = -0.48, p < 0.05) at follow-up (20 months). The magnitude of associations was half in magnitude and remained significant (p < 0.05) when reallocating 15 min of sedentary time into MVPA. Reallocating sedentary time into light physical activity was not related (p > 0.05) with body fatness outcomes. CONCLUSIONS: Substituting sedentary time with MVPA using isotemporal analysis is associated with positive effects on body composition. PMID- 27256489 TI - A Phytophthora sojae effector suppresses endoplasmic reticulum stress-mediated immunity by stabilizing plant Binding immunoglobulin Proteins. AB - Phytophthora pathogens secrete an array of specific effector proteins to manipulate host innate immunity to promote pathogen colonization. However, little is known about the host targets of effectors and the specific mechanisms by which effectors increase susceptibility. Here we report that the soybean pathogen Phytophthora sojae uses an essential effector PsAvh262 to stabilize endoplasmic reticulum (ER)-luminal binding immunoglobulin proteins (BiPs), which act as negative regulators of plant resistance to Phytophthora. By stabilizing BiPs, PsAvh262 suppresses ER stress-triggered cell death and facilitates Phytophthora infection. The direct targeting of ER stress regulators may represent a common mechanism of host manipulation by microbes. PMID- 27256490 TI - The effect of different combinations of local anaesthesia, sedative and non steroidal anti-inflammatory drugs on daily growth rates of dairy calves after disbudding. AB - AIM: To assess the effect of sedation and local anaesthesia (LA) at disbudding, and the addition of meloxicam or ketoprofen treatment, on weight gain in dairy calves following disbudding. METHODS: Friesian-Jersey cross calves, from four dairy farms, were enrolled when 3-6 weeks old. All calves (n=271) were disbudded by veterinary personnel and randomly assigned to six groups: 136 were disbudded without sedation or LA, of which 31 received 20 mg meloxicam S/C and 75 received 150 mg ketoprofen I/M. A further 135 were disbudded with sedation (0.25 mg/kg xylazine I/M) and LA, of which 30 also received meloxicam and 75 received ketoprofen. Calves were weighed 3 days before, and 15 and 30 days after, disbudding (Day 0). Daily weight gain was analysed using mixed models and ANOVA. RESULTS: Complete results were obtained from 263 calves. From Day -3 to Day 15, the growth rate of calves disbudded without pain relief (0.53 (95% CI=0.47-0.60) kg/day) was less that of calves disbudded with some form of pain relief (0.65 (95% CI=0.62-0.68) kg/d; p=0.004). There was no difference between the effect of meloxicam or ketoprofen (p=1.00). An interaction between use of sedation and LA and additional non-steroidal anti-inflammatory drugs (NSAID) meant that NSAID treatment did not increase growth rates in calves disbudded with sedation and LA but did increase growth rates for calves disbudded without pain relief (p<0.05). From Day 16 to Day 30 there was no effect of NSAID treatment on growth rate, but calves receiving LA and sedation grew faster (0.74 (95% CI=0.69-0.80) kg/day) than calves disbudded without LA and sedation (0.66 (95% CI=0.61-0.71) kg/day; p=0.018). From Day -3 to Day 30, calves disbudded with sedation and LA grew faster (0.71 (95%CI=0.64-0.77) kg/day) than calves disbudded without sedation and LA (0.60 (95% CI=0.55-0.65) kg/day; p=0.011). However, addition of NSAID to sedation and LA made no further difference to growth rates (p=0.69). CONCLUSIONS: Dairy calves disbudded with no pain relief had slower growth rates than calves receiving pain relief. From Day 15 to 30 calves given no pain relief, or NSAID alone, grew more slowly than those receiving sedation and LA at disbudding. The addition of NSAID treatment to sedation and LA did not further increase growth rates. CLINICAL RELEVANCE: This study adds to the evidence that pain management when disbudding is beneficial for calf productivity as well as calf welfare. PMID- 27256492 TI - Eigenstress model for electrochemistry of solid surfaces. AB - Thermodynamic analysis and molecular dynamics simulations were conducted to systematically study the size-dependent electrochemical response of solids. By combining the generalized Young-Laplace equation with the popular Butler-Volmer formulation, the direct influence of surface stress on solid film electrochemical reactions was isolated. A series of thermodynamic formulas were developed to describe the size-dependent electrochemical properties of the solid surface. These formulas include intrinsic surface elastic parameters, such as surface eigenstress and surface elastic modulus. Metallic films of Au, Pt, Ni, Cu and Fe were studied as examples. The anodic current density of the metal film increased, while the equilibrium potential decreased with increasing solid film thickness. PMID- 27256491 TI - Association between Leukoaraiosis and Poor Outcome is not due to Reperfusion Inefficiency after Intravenous Thrombolysis. AB - Leukoaraiosis (LA) is associated with structural and functional cerebrovascular impairment, which may compromise the capacity of ischemic tissue to maximize reperfusion after intravenous thrombolysis (IVT). We aimed to determine whether severe LA is correlated with reperfusion inefficiency, which contributes to infarct growth and poor functional outcome. We analyzed data from our consecutive acute ischemic stroke (AIS) patients who had acquired baseline and 24-h follow-up diffusion- and perfusion-weighted imaging. Reperfusion was defined as reduction of >=70 % of hypoperfusion lesion at 24 h from baseline. Severe LA was defined as Fazekas score 2 or 3 on FLAIR images. We investigated the relationship between severity of LA and reperfusion status. Multivariate statistical analysis was carried out for modeling the independent predictors of reperfusion, infarct growth, and functional outcome. Finally, 79 patients were included, among them 30 (37.97 %) had severe LA. Reperfusion was observed in 41 (51.89 %) patients, the proportion of reperfusion was very similar in patients with and without severe LA (53.33 vs 51.02 %, p = 1.000). Large artery occlusion was the only independent unfavorable predictor for reperfusion (OR = 0.202, 95 % confidence interval, 0.060-0.673; p = 0.014). Multiple linear regression analysis revealed that severe LA was independently associated with infarct growth (standardized coefficients = 0.191, p = 0.040). Severe LA was also an independent predictor of poor outcome (mRS >= 3) (OR = 4.004, 95 % confidence interval, 1.267-12.656, p = 0.018) after adjusting for reperfusion and baseline severity of stroke. Severe LA was associated with infarct growth and poor outcome independent of reperfusion status, which may expand the notion that LA contributes the intrinsic vulnerability of brain tissue to acute ischemic insults. The burden of LA may not serve as an imaging indicator of reperfusion inefficiency after IVT for AIS patients. PMID- 27256493 TI - A Gendered Analysis of the Effects of Social Ties and Risky Behavior on Intimate Partner Violence Victimization. AB - Recent studies have begun to explore how social ties relate to adolescent dating violence. Building upon prior literature that investigates the relationship between lifestyle patterns and dating violence, the current research explores how social ties developed early in life may indirectly affect intimate partner violence (IPV) victimization risk among adults by influencing risky behavior in late adolescence. Furthermore, the study explores the possibility that the relationship between social ties, risk behavior, and IPV may be gendered. To examine the direct and indirect effects, the current study uses data from three waves of the National Longitudinal Study of Adolescent Health (Add Health) to estimate multiple mediation models. Peer engagement and adolescent risky behavior have significant direct effects on IPV risk in young adulthood. Tests of indirect effects provide evidence of mediation with the social tie measures indirectly influencing IPV risk via their influence on risky behavior. Finally, there is evidence that the pathways to IPV victimization vary by sex. Implications for theory and policy, and directions for future research are discussed. PMID- 27256494 TI - Heterogeneity Within Domestic Violence Exposure: Young Adults' Retrospective Experiences. AB - Using Holden's taxonomy of domestic violence (DV) exposure as a guiding framework, the current study examined young adults' diverse DV exposure experiences. Twenty-five young adults (ages 19-25) exposed to father-perpetrated DV during their childhood and adolescence were interviewed using a qualitative descriptive design. Data analyses focused on coercive control exposure through reports of non-physical abuse tactics, types of exposure (e.g., direct, indirect), physical violence exposure (e.g., severity, frequency), and child abuse and harsh parenting practices. DV-exposed young adults were directly and indirectly exposed to physical violence and an array of non-physical abuse tactics toward their mothers. Young adults categorized as having been exposed to coercive controlling violence reported exposure to ongoing, non-physical abuse tactics and more frequent and severe physical violence. These young adults were also more likely to intervene and become victimized during physical violence and reported repeated episodes of child abuse and harsh parenting. Although coercive control appeared to be associated with physical violence and child abuse, generalizations should be made with caution as a few participants exposed to situational conflict were exposed to frequent and severe DV. The findings suggest that DV exposure should be measured in methodologically sophisticated ways to capture the heterogeneity in experiences, with the goal of promoting empirically driven intervention and prevention initiatives that are tailored to individual and family needs. PMID- 27256495 TI - Intimate Partner Violence Among Same-Sex Couples in College: A Propensity Score Analysis. AB - Intimate partner violence (IPV) is a pervasive social issue with numerous detrimental effects on individuals, families, and society. Existing research and a social-ecological minority stress framework suggest, as compared with mixed-sex couples, those in same-sex relationships may be at heightened risk for perpetrating and experiencing IPV. Using a U.S. sample of college students (N = 4,081), this secondary data analysis contrasted the prevalence of five forms of IPV (i.e., physical, sexual, psychological, injury, any type) between those in mixed-sex (n = 3,960) and those in same-sex (n = 121) intimate partnerships. Comparative analyses were supplemented with propensity score weighting to help balance members of mixed-sex and same-sex relationships across eight potentially confounding variables (e.g., biological sex, age). Prior to the application of propensity score weighting, results suggested those in same-sex relationships are significantly more likely to perpetrate and/or experience IPV resulting in physical injury. Results from post-weighting analyses retained the significance and magnitude of model estimates. Taken together, results suggest, as compared with mixed-sex couples, U.S. college students in same-sex couples have greater odds of experiencing IPV perpetration and victimization resulting in physical injury, even after accounting for the influence of several potentially confounding variables. Findings support the utility and future application of propensity score analytic techniques in this type of research as well as the importance of recognizing the unique IPV risk and service needs of people in same sex relationships. PMID- 27256496 TI - Amyopathic Dermatomyositis: A Concise Review of Clinical Manifestations and Associated Malignancies. AB - Amyopathic dermatomyositis is a rare, idiopathic, connective tissue disease that presents with dermatologic lesions of classic dermatomyositis but lacks the myopathy of this disease. Cutaneous manifestations may include Gottron's sign, heliotrope rash, and characteristic patterns of poikiloderma. There is a substantial risk for developing interstitial lung disease or malignancy in patients with amyopathic dermatomyositis. A literature review of amyopathic dermatomyositis was performed using the PubMed medical database. The key features of amyopathic dermatomyositis, including autoantibodies, clinical presentation and dermatologic manifestations, epidemiology, history, associated malignancies, management, and pathogenesis, are summarized in this review. Cancer (solid tumor) (73/79, 89 %) and hematologic malignancies (9/79, 11 %) were reported in 79 patients, with three patients having more than one malignancy. In addition, there were six patients with amyopathic dermatomyositis who had tumor of unknown primary, and eight patients with cancer-associated amyopathic dermatomyositis for whom no additional details were provided. From the group of 73 tumors for whom primary origin and sex were available, malignancy of the genitourinary organs (24/73, 33 %), aerorespiratory organs (15/73, 21 %), and breast (14/73, 19 %) were the most commonly observed solid organ tumors. Tumors of the genitourinary organs (15/48, 31 %) and breast (14/48, 29 %) were the most frequent neoplasms in women, accounting for 29 of 48 (60 %) cancers, with the most common sites being breast (14/48, 29 %), ovary (8/48, 17 %), and cervix or uterus (5/48, 10 %). In men, tumors of the aerorespiratory (9/25, 36 %) and genitourinary (9/25, 36 %) tracts were the most common neoplasms, accounting for 72 % (18/25) of cancers; the most common sites of primary malignancy were nasopharyngeal (6/25, 24 %), bladder (4/25, 16 %), and either colorectal, lung or prostate cancer (three cancers each, 12 %). In summary, the search for an undiagnosed associated malignancy in patients with amyopathic dermatomyositis should focus towards the organs most frequently affected. Similar to classic dermatomyositis, ovarian and nasopharyngeal cancers are also common in amyopathic dermatomyositis. However, in contrast to lung cancer, which is the most frequent malignancy associated with classic dermatomyositis, breast cancer was the most common type of malignancy reported in patients with amyopathic dermatomyosotis. PMID- 27256497 TI - Management of Pain Associated with Selected Conditions in Dermatology. AB - Dermatologists face a wide range of pain control challenges in daily practice, from the transient pain of dermatologic surgery to the persistent pain that plagues some chronic dermatologic conditions. Although the pathophysiology of pain is well described and the profound impact of dermatological pain on patients' quality of life is well appreciated, there is an identified need for clear therapeutic plans for providing symptomatic pain relief of common painful dermatoses. In this paper, we will review and clearly outline approaches to pain management of a number of common painful dermatoses such as herpes zoster and post-herpetic neuralgia, ulcers, oral dermatoses, dysesthesias, and many others. PMID- 27256498 TI - Oxidative Status Profile in Different Tissues of Parastacus brasiliensis promatensis (Crustacea, Decapoda, Parastacidae) over a Seasonal Cycle. AB - The objective of this study was to assess annual redox balance by quantifying activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), as well as measuring lipid peroxidation levels by determination of thiobarbituric acid-reactive substances, in different tissues of male and female crayfish collected from an area little affected by anthropogenic impacts. A total of 37 male and 32 female of Parastacus brasiliensis promatensis were collected over an annual cycle, and gill, muscle, hepatopancreas, and gonad samples were harvested and subjected to the aforementioned analyses via spectrophotometry. Comparison of the annual oxidative status response profile in gill and in hepatopancreas between males and females revealed differences only in SOD activity. In abdominal muscle, this comparison revealed a distinct profile of SOD and GST activity, as well as of lipid peroxidation. SOD activity in gonads of females increased in the summer when compared to autumn; conversely, CAT and GST levels did not differ over the year. During reproduction, a possible increase of the energy requirements led to an increase in lipid peroxidation in all tested tissues, in males and females alike. It was least evident in female gonad tissue, which suggests this tissue type is relatively protected; within this context, one may establish a tissue-specific grading of Lipid Peroxidation intensity in females of the species during the spring: gonads < muscle < gills < hepatopancreas. Our results show that the responses of the defenses analyzed antioxidants, as well as lipid peroxidation levels, were sex and tissue dependent and a clear pattern of seasonal variation. PMID- 27256499 TI - Bed nucleus of the stria terminalis NMDA receptors and nitric oxide modulate contextual fear conditioning in rats. AB - The bed nucleus of the stria terminalis (BNST) modulates anxiety-like responses, including conditioned emotional responses. Evidence suggests that glutamatergic neurotransmission in the BNST plays a role in the modulation of defensive responses. However, little is known about the involvement of glutamate NMDA receptor activation within the BNST, and its resultant increase in nitric oxide (NO) levels, in the expression of contextual fear conditioning (CFC). We investigated whether the antagonism of NMDA receptors or the reduction of NO levels in the BNST would attenuate behavioral and autonomic responses (i.e. increase in arterial pressure and heart rate, and decrease in tail cutaneous temperature) of rats submitted to a CFC paradigm. Intra-BNST infusion of AP7, an NMDA receptor antagonist, attenuated both behavioral and autonomic changes induced by CFC. Similar results were observed with NPLA and c-PTIO, an nNOS inhibitor and an NO scavenger, respectively. A positive correlation between BNST NO levels and the time spent in freezing behavior was also observed for animals submitted to the CFC. These findings indicate that the expression of CFC involves a facilitation of BNST NMDA receptor-NO signaling. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. PMID- 27256500 TI - Fluoxetine and vitamin C synergistically inhibits blood-spinal cord barrier disruption and improves functional recovery after spinal cord injury. AB - Recently we reported that fluoxetine (10 mg/kg) improves functional recovery by attenuating blood spinal cord barrier (BSCB) disruption after spinal cord injury (SCI). Here we investigated whether a low-dose of fluoxetine (1 mg/kg) and vitamin C (100 mg/kg), separately not possessing any protective effect, prevents BSCB disruption and improves functional recovery when combined. After a moderate contusion injury at T9 in rat, a low-dose of fluoxetine and vitamin C, or the combination of both was administered intraperitoneally immediately after SCI and further treated once a day for 14 d. Co-treatment with fluoxetine and vitamin C significantly attenuated BSCB permeability at 1 d after SCI. When only fluoxetine or vitamin C was treated after injury, however, there was no effect on BSCB disruption. Co-treatment with fluoxetine and vitamin C also significantly inhibited the expression and activation of MMP-9 at 8 h and 1 d after injury, respectively, and the infiltration of neutrophils (at 1 d) and macrophages (at 5 d) and the expression of inflammatory mediators (at 2 h, 6 h, 8 h or 24 h after injury) were significantly inhibited by co-treatment with fluoxetine and vitamin C. Furthermore, the combination of fluoxetine and vitamin C attenuated apoptotic cell death at 1 d and 5 d and improved locomotor function at 5 weeks after SCI. These results demonstrate the synergistic effect combination of low-dose fluoxetine and vitamin C on BSCB disruption after SCI and furthermore support the effectiveness of the combination treatment regimen for the management of acute SCI. PMID- 27256502 TI - Risk of incident atrial fibrillation with hypomagnesemia. PMID- 27256501 TI - Inhaled delivery of Delta(9)-tetrahydrocannabinol (THC) to rats by e-cigarette vapor technology. AB - Most human Delta(9)-tetrahydrocannabinol (THC) use is via inhalation, and yet few animal studies of inhalation exposure are available. Popularization of non combusted methods for the inhalation of psychoactive drugs (Volcano((r)), e cigarettes) further stimulates a need for rodent models of this route of administration. This study was designed to develop and validate a rodent chamber suitable for controlled exposure to vaporized THC in a propylene glycol vehicle, using an e-cigarette delivery system adapted to standard size, sealed rat housing chambers. The in vivo efficacy of inhaled THC was validated using radiotelemetry to assess body temperature and locomotor responses, a tail-flick assay for nociception and plasma analysis to verify exposure levels. Hypothermic responses to inhaled THC in male rats depended on the duration of exposure and the concentration of THC in the vehicle. The temperature nadir was reached after ~40 min of exposure, was of comparable magnitude (~3 degrees Celsius) to that produced by 20 mg/kg THC, i.p. and resolved within 3 h (compared with a 6 h time course following i.p. THC). Female rats were more sensitive to hypothermic effects of 30 min of lower-dose THC inhalation. Male rat tail-flick latency was increased by THC vapor inhalation; this effect was blocked by SR141716 pretreatment. The plasma THC concentration after 30 min of inhalation was similar to that produced by 10 mg/kg THC i.p. This approach is flexible, robust and effective for use in laboratory rats and will be of increasing utility as users continue to adopt "vaping" for the administration of cannabis. PMID- 27256503 TI - Coping With Logical Fallacies: A Developmental Training Program for Learning to Reason. AB - This study trained children to master logical fallacies and examined how learning is related to processing efficiency and fluid intelligence (gf). A total of one hundred and eighty 8- and 11-year-old children living in Cyprus were allocated to a control, a limited (LI), and a full instruction (FI) group. The LI group learned the notion of logical contradiction and the logical structure of the schemes involved. The FI group learned, additionally, to recognize other deductive reasoning principles. Reasoning improved proportionally to training. Awareness improved equally in LI and FI. Changes in reasoning and awareness changes were related to attention control and gf. Awareness mediated the influence of training on reasoning but not vice versa, suggesting that awareness is necessary for conditional reasoning. Implications are discussed. PMID- 27256504 TI - Aqueous synthesis of LiFePO4 with Fractal Granularity. AB - Lithium iron phosphate (LiFePO4) electrodes with fractal granularity are reported. They were made from a starting material prepared in water by a low cost, easy and environmentally friendly hydrothermal method, thus avoiding the use of organic solvents. Our method leads to pure olivine phase, free of the impurities commonly found after other water-based syntheses. The fractal structures consisted of nanoparticles grown into larger micro-sized formations which in turn agglomerate leading to high tap density electrodes, which is beneficial for energy density. These intricate structures could be easily and effectively coated with a thin and uniform carbon layer for increased conductivity, as it is well established for simpler microstructures. Materials and electrodes were studied by means of XRD, SEM, TEM, SAED, XPS, Raman and TGA. Last but not least, lithium transport through fractal LiFePO4 electrodes was investigated based upon fractal theory. These water-made fractal electrodes lead to high-performance lithium cells (even at high rates) tested by CV and galvanostatic charge-discharge, their performance is comparable to state of the art (but less environmentally friendly) electrodes. PMID- 27256505 TI - Neuronal expression of ILEI/FAM3C and its reduction in Alzheimer's disease. AB - Decrease in brain amyloid-beta (Abeta) accumulation is a leading strategy for treating Alzheimer's disease (AD). However, the intrinsic mechanism of the regulation of brain Abeta production is largely unknown. Previously, we reported that ILEI (also referred to as FAM3C) binds to the gamma-secretase complex and suppresses Abeta production without inhibiting gamma-secretase activity. In this study, we examined ILEI expression in mouse brain using immunohistochemistry and subcellular fractionation. Brain ILEI showed widespread expression in neurons and ependymal cells but not in glial and vascular endothelial cells. Neuronal ILEI resided in perinuclear vesicular structures, which were positive for a marker protein of the trans-Golgi network. Although ILEI immunostaining was negative at synaptic terminals, synaptosome fractionation analysis suggested that ILEI was enriched in presynaptic terminals, particularly in the active zone-docked synaptic vesicles. ILEI expression levels in brain peaked during the postnatal period and declined with age. In comparison with age-matched control brains, the number of ILEI-immunoreactive neurons decreased in AD brains, although the subcellular localization was unaltered. Our results suggest that a decline of ILEI expression may cause accumulation of Abeta in the brain and the eventual development of AD. PMID- 27256506 TI - GAPDH/Siah1 cascade is involved in traumatic spinal cord injury and could be attenuated by sivelestat sodium. AB - The glyceraldehyde-3-phosphate dehydrogenase (GAPDH)/Siah1 signaling pathway has been recognized as a sensor of nitric oxide (NO). It is associated with a variety of injurious conditions, suggesting its therapeutic potential for spinal cord injury (SCI). Sivelestat sodium (SIV), a neutrophil elastase (NE) inhibitor initially used to treat acute lung injury, has been known to protect against compression-induced and ischemic SCI. However, little is known about the relationship between the GAPDH/Siah1 cascade and SIV. Thus, we aimed to assess the role of GAPDH/Siah1 cascade in traumatic SCI and its possible link with SIV. Rats were assigned to four groups: sham group, SCI group, 5-mg/kg SIV group, and 10-mg/kg SIV. The traumatic SCI was induced by dropping a 10-g impactor from a height of 25mm on the dorsal surface of T9 and T10. SIV was injected intraperitoneally immediately after surgery. Our results showed that the nuclear translocation of GAPDH was induced together with the nuclear translocation of Siah1 and the formation of the GAPDH/Siah1 complex in the spinal cord after traumatic SCI. However, the activation of the GAPDH/Siah1 cascade was attenuated by treatment with SIV. We also found that SIV suppressed apoptosis, NE and inducible nitric oxide synthase (iNOS) protein expressions, the number of NE and iNOS immunostained cells, the production of interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha), and the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-kappaB) signaling in the spinal cord. The behavioral tests showed that SIV promoted functional recovery after traumatic SCI as reflected in the sustained increase in the Basso-Beattie Bresnahan (BBB) scores throughout the observation period. In conclusion, our results reveal GAPDH/Siah1 as a novel signaling pathway during the progression of SCI, which can be blocked by SIV. PMID- 27256507 TI - 17beta-Estradiol infusions into the dorsal striatum rapidly increase dorsal striatal dopamine release in vivo. AB - Systemic injections of 17beta-estradiol (E2) in ovariectomized (OVX) female rats rapidly enhance dorsal striatal dopamine (DA) release in response to amphetamine (AMPH). Additionally, a single injection of E2 rapidly (within 30min) enhances amphetamine-induced DA release. In situ studies show that this rapid effect of E2 occurs specifically within the dorsal striatum (DS). The present study investigated the in vivo effects of E2 infused into the DS, medial prefrontal cortex (mPFC) or the substantia nigra (SN) on dorsal striatal DA release. Rats were OVX and implanted with a silastic tube containing 5% E2 in cholesterol, previously shown to mimic low physiological serum concentrations of 18-32pg/ml. Single-probe microdialysis was used to measure extracellular DA levels in the DS. In addition, DA release was measured subsequent to systemic injections of the indirect DA agonist, AMPH (0.5mg/kg SC), administered simultaneously with E2 (0.544MUg/100MUl) or its vehicle, cyclodextrin (VEH) (0.520MUg/100MUl). Local infusions of E2 into the DS resulted in a greater amphetamine-induced dorsal striatal DA release in comparison to vehicle. Local infusions of E2 into the mPFC or the SN did not result in an enhancement of amphetamine-induced DA levels in the DS. These studies suggest that increases in dorsal striatal DA release in response to systemic E2 are a consequence of E2 actions within the DS itself. PMID- 27256509 TI - Diet quality and cognitive function in an urban sample: findings from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. AB - OBJECTIVE: Poor diet quality contributes to morbidity, including poor brain health outcomes such as cognitive decline and dementia. African Americans and individuals living in poverty may be at greater risk for cognitive decrements from poor diet quality. DESIGN: Cross-sectional. SETTING: Baltimore, MD, USA. SUBJECTS: Participants were 2090 African Americans and Whites (57 % female, mean age=47.9 years) who completed two 24 h dietary recalls. We examined cognitive performance and potential interactions of diet quality with race and poverty status using baseline data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Healthy Eating Index-2010 (HEI-2010) scores were calculated and interpreted using federal guidelines. A neurocognitive test battery was administered to evaluate cognitive function over several domains. RESULTS: Linear regression analyses showed that lower HEI-2010 scores were associated with poorer verbal learning and memory (P<0.05) after adjustment for covariates. Diet quality within the sample was poor. Significant interactions of HEI-2010 and poverty status (all P<0.05) indicated that higher diet quality was associated with higher performance on tests of attention and cognitive flexibility, visuospatial ability and perceptual speed among those below the poverty line. No significant race interactions emerged. Higher diet quality was associated with better performance on two measures of verbal learning and memory, irrespective of race and poverty status. CONCLUSIONS: Findings suggest that diet quality and cognitive function are likely related at the population level. Future research is needed to determine whether the association is clinically significant. PMID- 27256508 TI - The intercalated nuclear complex of the primate amygdala. AB - The organization of the inhibitory intercalated cell masses (IM) of the primate amygdala is largely unknown despite their key role in emotional processes. We studied the structural, topographic, neurochemical and intrinsic connectional features of IM neurons in the rhesus monkey brain. We found that the intercalated neurons are not confined to discrete cell clusters, but form a neuronal net that is interposed between the basal nuclei and extends to the dorsally located anterior, central, and medial nuclei of the amygdala. Unlike the IM in rodents, which are prominent in the anterior half of the amygdala, the primate inhibitory net stretched throughout the antero-posterior axis of the amygdala, and was most prominent in the central and posterior extent of the amygdala. There were two morphologic types of intercalated neurons: spiny and aspiny. Spiny neurons were the most abundant; their somata were small or medium size, round or elongated, and their dendritic trees were round or bipolar, depending on location. The aspiny neurons were on average slightly larger and had varicose dendrites with no spines. There were three non-overlapping neurochemical populations of IM neurons, in descending order of abundance: (1) Spiny neurons that were positive for the striatal associated dopamine- and cAMP-regulated phosphoprotein (DARPP-32+); (2) Aspiny neurons that expressed the calcium-binding protein calbindin (CB+); and (3) Aspiny neurons that expressed nitric oxide synthase (NOS+). The unique combinations of structural and neurochemical features of the three classes of IM neurons suggest different physiological properties and function. The three types of IM neurons were intermingled and likely interconnected in distinct ways, and were innervated by intrinsic neurons within the amygdala, or by external sources, in pathways that underlie fear conditioning and anxiety. PMID- 27256510 TI - Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology. AB - Renal fibrosis is one of the important pathways involved in end-stage renal failure. Investigating the metabolic changes in the progression of disease may enhance the understanding of its pathogenesis and therapeutic information. In this study, (1)H-nuclear magnetic resonance (NMR)-based metabonomics was firstly used to screen the metabolic changes in urine and kidney tissues of renal interstitial fibrotic rats induced by unilateral ureteral obstruction (UUO), at 7, 14, 21, and 28 days after operation, respectively. The results revealed that reduced levels of bioenergy synthesis and branched chain amino acids (BCAAs), as well as elevated levels of indoxyl sulfate (IS) are involved in metabolic alterations of renal fibrosis rats. Next, by pharmacological treatment we found that reduction of IS levels could prevent the renal fibrotic symptoms. Therefore, we suggested that urinary IS may be used as a potential biomarker for the diagnosis of renal fibrosis, and a therapeutic target for drugs. Novel attempt combining metabonomics and pharmacology was established that have ability to provide more systematic diagnostic and therapeutic information of diseases. PMID- 27256511 TI - Serial outcomes in acute necrotising encephalopathy of childhood: A medium and long term study. AB - OBJECTIVE: Acute necrotising encephalopathy (ANEC) is a severe, debilitating childhood disorder. We used the ANEC scoring system (ANE-ss) and standardised neurodevelopmental scores to objectively characterise medium and long term outcomes. METHODS: Retrospective review of children with ANEC at KK Women's and Children's Hospital, Singapore, from 2005 to 2012. ANE-ss was determined from clinical features and neuroimaging, and neurodevelopmental scores (Pediatric Glasgow Outcome Scale Extended, Pediatric Cerebral Performance Category scale and Pediatric Overall Performance Category scale) were applied at 1, 6, 12 and 24months post diagnosis. RESULTS: Seven patients with ANEC were studied. All had a viral prodrome with fever, and encephalopathy at presentation, and received immunotherapy (steroids or immunoglobulin). ANE-ss scores were medium risk in 4 patients and high risk in 3 patients. One died (high risk ANE-ss) and outcome was determined in the 6 survivors. At 1month post diagnosis, 3 patients (50%) were mildly affected and 3 (50%) were severely affected. Morbidity rates improved by 12months, with 67% and 33.3% scoring in the mildly affected and severely affected ranges, respectively. Medium risk patients did well with majority having little or no neurological deficits and good outcome scores. CONCLUSION: Mortality and severe morbidity correlated well with high risk ANE-ss. However, our patients with medium risk ANE-ss had good neurodevelopmental sequelae. Serial disability scoring is useful in evaluating the progress of ANEC patients on follow up. Assessment at 1month post diagnosis can aid prognostication of long term outcome. PMID- 27256512 TI - Arts syndrome with a novel missense mutation in the PRPS1 gene: A case report. AB - Arts syndrome is characterized by early-onset hypotonia, ataxia, intellectual disability, sensorineural hearing impairment, progressive optic atrophy, and a tendency to develop infections. Arts syndrome is an X-linked disorder caused by a loss-of-function mutation in the PRPS1 gene, which encodes phosphoribosylpyrophosphate synthetase 1. Only three families have been reported. Here, we report another family with Arts syndrome. The initial symptoms of the 1 year-old proband were hypotonia and ataxia, worsening recurrent infection triggered muscle weakness, motor and intellectual developmental delay, and hearing loss. Both central nervous system involvement and peripheral neuropathy were demonstrated. His three maternal uncles had died before the age of 3years. A genetic analysis of PRPS1 revealed a novel missense mutation, c.367C>G (p.His123Asp). PRPS enzymatic activity was markedly reduced in the patient. His mother was supposed to be an asymptomatic carrier. Arts syndrome should be included in the differential diagnosis of infantile hypotonia and weakness aggravated by recurrent infection with a family history of X-linked inheritance. PMID- 27256513 TI - Dynamic-field devices for the ultrasonic manipulation of microparticles. AB - The use of acoustic radiation forces in lab-on-a-chip environments has seen a rapid development in recent years. Operations such as particle sieving, sorting and characterisation are becoming increasingly common with a range of applications in the biomedical sciences. Traditionally, these applications rely on static patterns of ultrasonic pressure and are often collectively referred to as ultrasonic standing wave devices. Recent years have also seen the emergence of devices which capitalise on dynamic and reconfigurable ultrasonic fields and these are the subject of this review. Dynamic ultrasonic fields lead to acoustic radiation forces that change with time. They have opened up the possibility of performing a wide range of manipulations such as the transport and rotation of individual particles or agglomerates. In addition, they have led to device reconfigurability, i.e. the ability of a single lab-on-a-chip device to perform multiple functions. This opens up the possibility of channel-less microfluidic devices which would have many applications, for example in biosensing and microscale assembly. This paper reviews the current state of the field of dynamic and reconfigurable ultrasonic particle manipulation devices and then discusses the open problems and future possibilities. PMID- 27256514 TI - Effects of bioirrigation of non-biting midges (Diptera: Chironomidae) on lake sediment respiration. AB - Bioirrigation or the transport of fluids into the sediment matrix due to the activities of organisms such as bloodworms (larvae of Diptera, Chironomidae), has substantial impacts on sediment respiration in lakes. However, previous quantifications of bioirrigation impacts of Chironomidae have been limited by technical challenges such as the difficulty to separate faunal and bacterial respiration. This paper describes a novel method based on the bioreactive tracer resazurin for measuring respiration in-situ in non-sealed systems with constant oxygen supply. Applying this new method in microcosm experiments revealed that bioirrigation enhanced sediment respiration by up to 2.5 times. The new method is yielding lower oxygen consumption than previously reported, as it is only sensitive to aerobic heterotrophous respiration and not to other processes causing oxygen decrease. Hence it decouples the quantification of respiration of animals and inorganic oxygen consumption from microbe respiration in sediment. PMID- 27256516 TI - Treatment failure in superficial basal cell carcinoma following treatment with photodynamic therapy: is this a result of underdiagnosis? PMID- 27256515 TI - Effect of in utero exposure to the atypical anti-psychotic risperidone on histopathological features of the rat placenta. AB - For clinical management of different forms of psychosis, both classical and atypical anti-psychotic drugs (APDs) are available. These drugs are widely prescribed, even during pregnancy considering their minimal extra-pyramidal side effects and teratogenic potential compared to classical APDs. Among AAPDs, risperidone (RIS) is a first-line drug of choice by physicians. The molecular weight of RIS is 410.49 g/mol; hence, it can easily cross the placental barrier and enter the foetal bloodstream. It is not known whether or not AAPDs like RIS may affect the developing placenta and foetus adversely. Reports on this issue are limited and sketchy. Therefore, this study has evaluated the effects of maternal exposure to equivalent therapeutic doses of RIS on placental growth, histopathological and cytoarchitectural changes, and to establish a relationship between placental dysfunction and foetal outcomes. Pregnant rats (n = 24) were exposed to selected doses (0.8, 1.0 and 2.0 mg/kg) of RIS from gestation days 6 21. These dams were sacrificed; their placentas and foetuses were collected, morphometrically examined and further processed for histopathological examination. This study revealed that in utero exposure to equivalent therapeutic doses of RIS during organogenesis-induced placental dystrophy (size and weight), disturbed cytoarchitectural organization (thickness of different placental layers), histopathological lesions (necrosis in trophoblast with disruption of trophoblastic septa and rupturing of maternal-foetal interface) and intrauterine growth restriction of the foetuses. It may be concluded that multifactorial mechanisms might be involved in the dysregulation of structure and function of the placenta and of poor foetal growth and development. PMID- 27256517 TI - Arthritis, comorbidities, and care utilization in veterans of operations enduring and Iraqi Freedom. AB - Veteran populations are known to have frequencies of arthritis higher than civilian populations. The aim of this study is to define the prevalence of arthritis among a cohort of veterans from ongoing U.S. military operations. A retrospective cohort study using Veterans Administration data sources for service connected disability, comorbidities, clinic utilization, and pharmacy utilization was conducted including veterans who deployed in service to operations in Afghanistan or Iraq, comparing veterans with a diagnosis of arthritis, arthritis plus back pain, and veterans with no pain diagnoses. The frequency of arthritis was 11.8%. Veterans with arthritis and arthritis plus back pain had greater frequencies of diabetes, hyperlipidemia, hypertension, and obesity compare to veterans with no pain diagnosis. Veterans with arthritis plus back pain had the highest pain clinic utilization and prescription use of opioids and anti inflammatories. Veterans with no pain diagnosis had higher frequencies of diagnosis and clinic utilization for mental health disorders. Arthritis is prevalent among the latest generation of combat veterans and is associated with diabetes, obesity, and cardiovascular comorbidities. The need for arthritis care and associated comorbidities is expected to increase as the Veterans Administration and the civilian health care sector assumes care of these veterans. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:682-687, 2017. PMID- 27256518 TI - Psychosocial interventions for internalised stigma in people with a schizophrenia spectrum diagnosis: A systematic narrative synthesis and meta-analysis. AB - It is acknowledged that people with a schizophrenia-spectrum diagnosis experience higher levels of stigma compared to any other mental health diagnosis. As a consequence, their experience of internalised stigma is likely to be the most detrimental and pervasive. Internalised stigma interventions have shown some benefits in those who experience serious mental illness including those with a schizophrenia-spectrum diagnosis. A systematic narrative review and meta-analysis were conducted examining the efficacy of internalised stigma interventions for people with a schizophrenia-spectrum diagnosis. Randomised Controlled Trials, controlled trials, and cohort studies were included and assessed against quality criteria. The search identified 12 studies; 7 randomised controlled trials, 3 cohort studies and 2 controlled trials. A variety of psychosocial interventions were utilised with the majority employing Cognitive Behaviour Therapy (CBT), psychoeducation and social skills training. The core outcomes used to examine the efficacy of the intervention were internalised stigma, self-esteem, empowerment, and functioning. The meta-analysis revealed an improvement in internalised stigma favouring the internalised stigma intervention but was not significant (5 RCTs, n=200). Self-efficacy and insight were significantly improved favouring the internalised stigma intervention. Internalised stigma interventions show promise in those with schizophrenia-spectrum diagnoses. Existing interventions have demonstrated small effects and employed small samples. Large scale RCTs are required to further develop the evidence base of more targeted interventions. PMID- 27256519 TI - Cryo-thermal therapy elicits potent anti-tumor immunity by inducing extracellular Hsp70-dependent MDSC differentiation. AB - Achieving control of metastatic disease is a long-sought goal in cancer therapy. Treatments that encourage a patient's own immune system are bringing new hopes in reaching such a goal. In clinic, local hyperthermia and cryoablation have been explored to induce anti-tumor immune responses against tumors. We have also developed a novel therapeutic modality of cryo-thermal treatment by alternating liquid nitrogen (LN2) cooling and radio frequency (RF) heating, and better therapeutic effect was achieved in treating metastatic cancer in animal model. In this study, we investigated the mechanism of systemic immune response elicited by cryo-thermal therapy. In the 4T1 murine mammary carcinoma model, we found that local cryo-thermal therapy resulted in a considerable reduction of distant lung metastases, and improved long-term survival. Moreover, results of tumor re challenge experiments indicated generation of a strong tumor-specific immune memory after the local treatment of primary tumors. Our further study indicated that cryo-thermal therapy caused an elevated extracellular release of Hsp70. Subsequently, Hsp70 induced differentiation of MDSCs into mature DCs, contributing to the relief of MDSCs-mediated immunosuppression and ultimately the activation of strong anti-tumor immune response. Our findings reveal new insight into the mechanism of robust therapeutic effects of cryo-thermal therapy against metastatic cancers. PMID- 27256520 TI - A new post-intoxication treatment of paraoxon and parathion poisonings using an evolved PON1 variant and recombinant GOT1. AB - Organophosphate (OP) based pesticides are highly toxic compounds that are still widely used in agriculture around the world. According to World Health Organization (WHO) data, it is estimated that between 250,000 and 370,000 deaths occur yearly around the globe as a result of acute intoxications by pesticides. Currently available antidotal drug treatments of severe OP intoxications are symptomatic, do not reduce the level of intoxicating OP in the body and have limited ability to prevent long-term brain damage. Pesticide poisonings present a special therapeutic challenge since in many cases, such as with parathion, their toxicity stems from their metabolites that inhibit the essential enzyme acetylcholinesterase. Our goal is to develop a new treatment strategy for parathion intoxication by combining a catalytic bioscavenger that rapidly degrades the intoxicating parathion-metabolite (paraoxon) in the blood, with a glutamate bioscavenger that reduces the elevated concentration of extracellular glutamate in the brain following OP intoxication. We report on the development of a novel catalytic bioscavenger by directed evolution of serum paraoxonase 1 (PON1) that effectively detoxifies paraoxon in-vivo. We also report preliminary results regarding the utilization of this PON1 variant together with a recombinant human enzyme glutamate oxaloacetate transaminase 1 (rGOT1), suggesting that a dual PON-GOT treatment may increase survival and recovery from parathion and paraoxon intoxications. PMID- 27256521 TI - Cerebral oxidative metabolism is decreased with extreme apnoea in humans; impact of hypercapnia. AB - KEY POINTS: The present study describes the cerebral oxidative and non-oxidative metabolism in man during a prolonged apnoea (ranging from 3 min 36 s to 7 min 26 s) that generates extremely low levels of blood oxygen and high levels of carbon dioxide. The cerebral oxidative metabolism, measured from the product of cerebral blood flow and the radial artery-jugular venous oxygen content difference, was reduced by ~29% at the termination of apnoea, although there was no change in the non-oxidative metabolism. A subset study with mild and severe hypercapnic breathing at the same level of hypoxia suggests that hypercapnia can partly explain the cerebral metabolic reduction near the apnoea breakpoint. A hypercapnia-induced oxygen-conserving response may protect the brain against severe oxygen deprivation associated with prolonged apnoea. ABSTRACT: Prolonged apnoea in humans is reflected in progressive hypoxaemia and hypercapnia. In the present study, we explore the cerebral metabolic responses under extreme hypoxia and hypercapnia associated with prolonged apnoea. We hypothesized that the cerebral metabolic rate for oxygen (CMRO2 ) will be reduced near the termination of apnoea, attributed in part to the hypercapnia. Fourteen elite apnoea-divers performed a maximal apnoea (range 3 min 36 s to 7 min 26 s) under dry laboratory conditions. In a subset study with the same divers, the impact of hypercapnia on cerebral metabolism was determined using varying levels of hypercapnic breathing, against the background of similar hypoxia. In both studies, the CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-internal jugular venous oxygen content difference. Non-oxidative cerebral metabolism was calculated from the ratio of oxygen and carbohydrate (lactate and glucose) metabolism. The CMRO2 was reduced by ~29% (P < 0.01, Cohen's d = 1.18) near the termination of apnoea compared to baseline, although non-oxidative metabolism remained unaltered. In the subset study, in similar backgrounds of hypoxia (arterial O2 tension: ~38.4 mmHg), severe hypercapnia (arterial CO2 tension: ~58.7 mmHg), but not mild-hypercapnia (arterial CO2 tension: ~46.3 mmHg), depressed the CMRO2 (~17%, P = 0.04, Cohen's d = 0.87). Similarly to the apnoea, there was no change in the non-oxidative metabolism. These data indicate that hypercapnia can partly explain the reduction in CMRO2 near the apnoea breakpoint. This hypercapnic-induced oxygen conservation may protect the brain against severe hypoxaemia associated with prolonged apnoea. PMID- 27256522 TI - Endocannabinoid receptor blockade increases hepatocyte growth factor and reduces insulin levels in obese women with polycystic ovary syndrome. PMID- 27256523 TI - [Application and prospect of digital technology in the field of orthodontics]. AB - The three-dimensional(3D)digital technology has brought a revolutionary change in diagnostic planning and treatment strategy of orthodontics. Acquisition of 3D image data of the hard and soft tissues of the patients, diagnostic analysis and treatment prediction, and ultimately the individualized orthodontic appliance, will become the development trend and workflow of the 3D orthodontics. With the development of 3D digital technology, the traditional plaster model has been gradually replacing by 3D digital models. Meanwhile, 3D facial soft tissue scan and cone-beam CT scan have been gradually applied to clinical orthodontics, making it possible to get 3D virtual anatomical structure for patients. With the help of digital technology, the diagnostic process is much easier for orthodontist. However how to command the whole digital workflow and put it into practice in the daily work is still a long way to go. The purpose of this article is to enlighten the orthodontists interested in digital technology and discuss the future of digital orthodontics in China. PMID- 27256524 TI - [Application of three-dimensional digital technology in the diagnosis and treatment planning in orthodontics]. AB - Three-dimensional(3D)digital technology has been widely used in the field of orthodontics in clinical examination, diagnosis, treatment and curative effect evaluation. 3D digital technology greatly improves the accuracy of diagnosis and treatment, and provides effective means for personalized orthodontic treatment. This review focuses on the application of 3D digital technology in the field of orthodontics. PMID- 27256525 TI - [Some technical problems in three-dimensional cephalometrics]. AB - Two-dimensional(2D)cephalometrics is an important diagnostic technique in dentistry. Three-dimensional(3D)cephalometrics is becoming a hot point along with the popularity of cone-beam CT(CBCT). However, the 3D cephalometric technique, like 2D cephalometric technique, there are many technical problems needed to be solved. In this article, several topics, including multi-source of 3D cephalometrics, the head position in 3D cephalometrics, the difficulty of landmark indication, norms for 3D cephalometrics and superimposition in 3D imaging, are discussed. PMID- 27256526 TI - [Preliminary safety and stability assessment of orthodontic miniscrew implantation guided by surgical template based on cone-beam CT images]. AB - OBJECTIVE: To develop surgical templates for orthodontic miniscrew implantation based on cone-beam CT(CBCT)three-dimensional(3D)images and to evaluate the safety and stability of implantation guided by the templates. METHODS: DICOM data obtained in patients who had CBCT scans taken were processed using Mimics software, and 3D images of teeth and maxillary bone were acquired. Meanwhile, 3D images of miniscrews were acquired using Solidworks software and processed with Mimics software. Virtual position of miniscrews was determined based on 3D images of teeth, bone, and miniscrews. 3D virtual templates were designed according to the virtual implantation plans. STL files were output and the real templates were fabricated with stereolithographic appliance(SLA). Postoperative CBCT scans were used to evaluate the implantation safety and the stability of miniscrews were investigated. RESULTS: All the templates were positioned accurately and kept stable throughout the implantation process. No root damage was found. The deviations were(1.73+/-0.65)mm at the corona, and(1.28+/-0.82)mm at the apex, respectively. The stability of miniscrews was fairly well. CONCLUSIONS: Surgical templates for miniscrew implantation could be acquired based on 3D CBCT images and fabricated with SLA. Implantation guided by these templates was safe and stable. PMID- 27256527 TI - [Clinical and radiologic characteristics of craniomaxillofacial primary tumor induced osteomalacia: a retrospective analysis]. AB - OBJECTIVE: To investigate the diagnosis strategy, radiology and clinical pathology feature of craniomaxillofacial primary tumor induced osteomalacia. METHODS: Twelve cases of craniomaxillofacial primary tumor induced osteomalacia were reviewed, including 5 male and 7 female with a age range from 16 to 69 years. The clinical characteristics, radiology examinations and pathological features were analyzed. RESULTS: The craniomaxillofacial primary tumor induced osteomalacia occurred in different ages, with 2 to 30 years of medical history. Seven of the twelve cases were octreotide scintigraphy positive, nine of the twelve cases invaded bone, exhibiting destruction of the adjacent cortex, ten of the twelve showed gingival lesions of local thickening or epulis. The tumor arises from mesenchymal tissue, infiltrating local gingiva and bone trabecular with spindle like fibroblasts and dental epithelial rests. CONCLUSIONS: The concealed nature of the tumor induced osteomalacia requires multiple methods to locate the primary tumor and the tumors located in craniomaxillofacial region have unique clinical and pathological features. PMID- 27256528 TI - [MRI interstitial (125)I seed implantation treatment for oral and maxillofacial adenogenic malignant tumor]. AB - OBJECTIVE: To assess the therapeutic efficacy of MRI guided interstitial (125)I seed implantation in the treatment of oral and maxillofacial adenogenic malignant tumor Methods: A total of 39 patients with oral and maxillofacial adenogenic malignant tumors received interstitial (125)I implantation treatment one week postoperatively. Before implantation, MRI scanning was performed and implantation plan of (125)I was designed with the aid of treating plan system. During the implantation, positioning pin was firstly implanted and then its position and direction were adjusted according to navigation. Next, (125)I was delivered into the target region. Real-time assessment was required to find if the sites of implantation corresponded with that of preoperative design. One week and two months after implantation, CT scanning and dosimetric analysis were performed. All the patients needed regular reexamination to observe if there was recurrence of tumor, lymphadenectasis in lymph draining region and distant metastasis. RESULTS: All the procedures of implantation were successful. Post-operative CT showed no seed migration and the location of implanted (125)I was exact as designed. Among the 39 patients, 7 cases suffered from tumor recurrence, with local control rate of 82%(32/29). One got pulmonary metastasis, and one had ipsilateral lymphadenectasis. No serious complications affected life quality, and no seeds migration was observed. CONCLUSIONS: MRI-guided implanting of (125)I is an accurate way to treat oral and maxillofacial adenogenic malignant tumors, which could effectively decrease postoperative complications and tumor recurrence rate. PMID- 27256529 TI - [Imaging analysis of temporomandibular joint anatomy changes after intraoral condylectomy combined with orthognathic surgery]. AB - OBJECTIVE: To quantitatively analyze the changes of facial symmetry and temporomandibular joint structure at different periods after intraoral condylectomy combined with orthognathic surgery, and to evaluate the long-term stability after the operation. METHODS: Spiral CT data of 10 cases treated by intraoral condylectomy combined with orthognathic surgery were collected, and then reconstructed by ProPlan software. Mark points were drawn on the 3D-images reconstructed immediately after the operation, and 6 months and 12 months after the operation. The measurements parameters included condylar axis angle in three dimensions, condylar-glenoid relative position and condylar facial morphology related indicators. The results were statistically analyzed by the consistency test and the variance of repeated measurement data. RESULTS: The facial asymmetry of the patients was corrected after operation, the height of the affected mandibular ascending ramus(T1: [67.81+/-6.95]mm, T2: [64.49+/-6.24]mm, T3: [63.05+/-7.07]mm)as well as the degree of pogonion deviation decreased(T1: [2.79+/-4.93]mm, T2: [0.37+/-4.20]mm, T3: [0.33 +/- 3.97]mm)(P<0.05). But the tilt angle of the occlusion plane and the degree of mandibular height asymmetry had no significant difference between all the post-operative periods(P>0.05). The post-operative 3D changes of the position and shape of the resected and its contralateral condylar showed that the bilateral condylar axis angle in the horizontal plane gradually grew after operation(affected condyle: 71.95 degrees +/- 7.47 degrees , 74.73 degrees +/-8.44 degrees , 76.56 degrees +/-5.22 degrees ; control condyle: 72.60 degrees +/-5.56 degrees , 76.00 degrees +/-5.30 degrees , 77.19 degrees +/-6.20 degrees and had significant difference between all the post-operative periods)(P<0.05), the condyle moved slowly upward on both sides(superior space on the affected side: [8.78+/-4.38]mm, [4.11+/-2.49]mm, [3.27+/-1.96]mm; on the control side: [3.63+/-1.49]mm, [2.52+/-1.19]mm, [2.38+/ 1.11]mm)(P<0.05), and moved inward only on the affected side(P< 0.05). All the above changes slowed down over time, and the disc-condyle-fossa relative position tended to be stable over time as well. The condyle diameter on the inside-outside direction gradually decreased on the affected side(T1: [14.98+/-2.39]mm, T2: [14.04+/-2.68]mm, T3: [13.74+/-2.89]mm)(P<0.05), and the surface morphology of the resected condyle was similar to the normal side. There were also some condylar surface morphological changes on the control side, but no statistical significance was found between different periods after the peration(P>0.05). CONCLUSIONS: The intraoral condylectomy combined with orthognathic surgery can eliminate condylar lesions effectively and correct the facial asymmetry caused by condylar benign tumor and hyperplasia. The facial symmetry can be maintained well after the operation, and the post-operative condylar morphology changes tended to be stable six months after the operation. PMID- 27256530 TI - [Influence of Coca-Cola on early erosion and surface microhardness of human enamel: an in situ study]. AB - OBJECTIVE: Assessed the effect of single dose attack of Coca-Cola on early erosion and surface microhardness of permanent human enamel, in order to provide diet instructions on minimum amount and frequency of carbonated beverage consumption. METHODS: Eighty enamel slabs were prepared out of 10 extracted human mandibular third molars, and distributed into 8 groups with randomized block design(n=10). Ten generally healthy volunteers with normal saliva secretion wore acrylic palatal appliances containing 2 enamel slabs, with formation of a salivary pellicle 2 h ahead. The volunteers were instructed to drink 100 ml fresh Coca-Cola within 20 s. And then the alterations of the enamel slabs were measured using a Vicker's microhardness tester at 1, 2, 4, 6, 8, 10, 20 and 30 min after the consumption of Coca-Cola. For each volunteer, the experiment was carried out in four days, 2 samples were examined each time. Data were analyzed using Kruskal Wallis and Wilcoxon tests(alpha =0.05). RESULTS: Significant decreases in surface microhardness(SMH)were observed in each time point(P<0.01). The percentages of surface microhardness changes on each exposure time were(12.2+/-3.9)%,(16.8+/ 5.5)%,(16.7+/-5.6)%,(16.2+/-6.2)%,(16.6+/-9.0)%,(15.6+/-3.7)%,(13.8+/-4.8)% and(11.4+/-3.2)%, respectively. Significant differences were observed between G1 min and G2-8 min(P=0.029), G2-8 min and G30 min(P=0.008). CONCLUSIONS: Single intake of 100 ml Coca-Cola could lead to significant decrease of enamel microhardness and initiate erosion of enamel surface. Enamel surface microhardness decreased to the lowest points at 2-8 min, and began to recover after 10 min. The enamel surface microhardness could not fully recovered to the baseline level in 30 min if no intervention was performed. PMID- 27256531 TI - [Finite element analysis of the maxillary central incisor with traditional and modified crown lengthening surgery and post-core restoration in management of crown-root fracture]. AB - OBJECTIVE: To construct three-dimensional finite element models with modified crown lengthening surgery and post-core restoration in management of various crown-root fracture types, to investigate the intensity and distribution of stressin models mentioned above, and to compare and analyze the indications of traditional and modified crown lengthening surgeries from the mechanic point of view. METHODS: Nine three-dimensional finite element models with modified crown lengthening surgery and post-core restoration were established and analyzed by micro-CT scanning technique, dental impression scanner, Mimics 10.0, Geomagic studio 9.0 and ANSYS 14.0 software. The von Mises stress of dentin, periodontal ligament, alveolar bone, post and core, as well as the periodontal ligament area and threshold limit value were calculated and compared with the findings of traditional crown lengthening models which had been published earlierby our research group. RESULTS: The von Mises stress intensity of modified crown lengthening models were: dentin>post>core>alveolar bone>periodontal ligament. The maximum von Mises stress of dentin(44.37-80.58 MPa)distributed in lingual central shoulder. The periodontal ligament area of the modified crown lengthening surgery was reduced by 6% to 28%, under the same crown-root fracture conditions, the periodontal ligament area of modified crown lengthening models was larger than that of the traditional crown lengthening models. In modified crown lengthening surgery models, the von Mises stress of periodontal ligament of B3L1m, B3L2m, B3L3m models exceeded their limit values, however, the von Mises stress of periodontal ligament of the B2L2c, B2L3c, B3L1c, B3L2c, B3L3c models exceeded their limit values in traditional crown lengthening surgery models. CONCLUSIONS: The modified crown lengthening surgery conserves more periodontal supporting tissues, which facilitates the long-term survival of teeth. The indication of modified crown lengthening surgery is wider than traditional method. The maxillary central incisors with labial fracture at gingival margin level and with palatal fracture at or below the alveolar crest level are not the indication of the crown lengthening surgery. PMID- 27256532 TI - [Inhibitory effect of quercetin on the biofilm formation of Streptococcus mutans]. AB - OBJECTIVE: To observe the inhibitory effect of quercetin on the biofilm formation of Streptococcus mutans(Sm), to preliminarily reveal the possible underlying mechanisms, and to evaluate the cytotoxicity of quercetion to human dental pulp cells so as to provide the theoretical basis for the application of quercetin in oral biomaterials. METHODS: Quercetin storage solution was diluted to 0, 3.125, 6.25, 12.5, 25, 50, 100, 200, 400 and 800 mg/L, and added into Sm medium for 4 h and 24 h, crystal violet staining was used to evaluate the biofilm volume. In subsequent detections, three groups were set: control(0 mg/L), 200 mg/L quercetin and 400 mg/L quercetin. Confocal laser scanning microscopy was used to observe the morphology of the biofilm; qPCR for gtfB, gtfC, comD, comE, and luxS were assessed to preliminarily investigate the mechanisms. Finally, the methyl thiazolyl tetrazolium(MTT)test using human dental pulp cells was used to investigate cytotoxicity. RESULTS: Quercetin could significantly inhibit up to(86.16+/-0.45)% of the biofilm formation of Sm(Compared with the control group P=0.00)and effectively removed(43.04+/-0.53)% of the mature biofilm(Compared with the control group P=0.00). Confocal laser scanning microscopy photographs showed that after co-incubated for 24 h, the dense biofilm structures of the experimental group were destroyed by quercetin both at 200 mg/L and 400 mg/L. Quercetin suppressedover 50% of the expression of gtfB, gtfC, comD, comE(compared with the control group P<0.05)and promoted the expression of luxS up to 2.18 +/- 0.24 and 2.84 +/- 0.26 after 4 h and 24 h, respectively(compared with the control group P<0.05). Quercetin also exhibited acceptable compatibility for human dental pulp cells. CONCLUSIONS: Quercetin could effectively reduce the biofilm formation of Sm by inhibiting the expression of the related genes, and exhibited no cytotoxicity for human dental pulp cells. Quercetin has good potential to be applied in oral biological materials. PMID- 27256533 TI - [Effects of recombinant human growth hormone on local expression of insulin-like growth factor-I during orthodontic tooth movement]. AB - OBJECTIVE: To explore in vivo the expression of insulin-like growth factor-I(IGF I)under stress, and to analyze changes of the local expression related to recombinant human growth hormone(rhGH)treatment. METHODS: Forty Wistar rats were randomly divided into control and growth hormone groups, 20 in each group. A force of 0.49 N was applied to move the right upper first molars mesially. The growth hormone group and control group received daily subcutaneous injections of rhGH and equivalent volumes of saline, respectively. The rats were sacrificed on days 1, 3, 7 and 14. Micro-CT-reconstructed images were used to survey root resorption, and horizontal sections of the maxillae were prepared for tartrate resistant acid phosphate(TRAP)and immunohistochemistry staining. RESULTS: Tooth moved faster in the growth hormone group([0.291+/-0.017], [0.513+/-0.111]mm)than in the control group([0.245+/-0.033], [0.368+/- 0.052]mm)on days 7 and 14(P<0.05). More osteoclasts on day 3, and fewer osteoclasts on day 7 were observed in the growth hormone group([4.0+/-0.7], [2.6+/-0.6]cell/high-power field)than in the control group([2.8+/-0.6], [3.8+/-0.8]cell/high-power field)(P<0.05). The number of IGF-I positive osteoclasts in the growth hormone group([4.7 +/- 0.7]cell/high-power field)was significantly greater than that in the control group([2.7+/-0.5]cell/high-power field)(P<0.01)on day 3. Compared with the control group([18.6+/-1.5], [23.3+/- 3.8]cell/high-power field), IGF-I positive PDL cells increased on days 7 and 14 in the growth hormone groups([29.6+/-3.4], [37.5+/-6.1]cell/high-power field)(P<0.01). CONCLUSIONS: rhGH could stimulate IGF-I expression in PDL, and accelerate bone remodeling and tooth movement. PMID- 27256535 TI - [Oral status of a child with Papillon-Lefevre syndrome: over 10-year follow-up]. PMID- 27256534 TI - [The progress in application of parathyroid hormone in craniomaxillofacial bone regeneration study]. AB - Parathyroid hormone(PTH)is synthesized and secreted by chief cell of Gley's glands which possesses dual functions of catabolism and anabolism. It regulates the proliferation and differentiation of multiple cell lines including osteoblast, osteoclast and skeletal lining cells. Furthermore, PTH activates various signaling pathways which control calcium, phosphorous' metabolism and bone conversion, accelerating the bone regeneration and reconstruction. However, the study of PTH in craniomaxillofacial bone regeneration is relatively less and whether the role of parathyroid glands and the mechanism of ossification are consistent with the long bone or not needs further investigation. This review focuses on the progress of PTH in craniomaxillofacial bone regeneration in recent years. PMID- 27256536 TI - Predictors of Incidence, Remission and Relapse of Axis I Mental Disorders in Young Women: A Transdiagnostic Approach. AB - : An understanding of etiological and maintaining factors of mental disorders is essential for the treatment of mental disorders, as well as mental health promotion and protection. The present study examines predictors of the incidence, remission and relapse of a wide range of Axis I mental disorders, using data from the Dresden Predictor Study. A sample of 1394 young German women completed questionnaires evaluating psychological factors (positive mental health, self efficacy, life satisfaction, neuroticism, psychopathology and dysfunctional attitudes) and global assessment of functioning, as well as structured diagnostic interviews assessing incidence and change (remission, relapse) in mental disorders. Predictors were analysed using a multivariate logistic regression model. Significant factors for incidence of mental disorders included neuroticism and global functioning. A remitting course of mental disorders was predicted by positive mental health, self-efficacy and global assessment of functioning. Relapse was significantly predicted by neuroticism and dysfunctional attitudes. Results imply that mental health promotion is particularly important for women with high neuroticism and low functioning, as they tend to be at risk for incidence. Mental disorder treatment may benefit from strengthening positive mental health and functioning, as these factors promote remission. Relapse prevention may benefit from attention to neuroticism and dysfunctional attitudes in order to reduce the likelihood of relapse. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Incidence of mental disorders in young women was predicted by neuroticism and low global functioning. There seems to be a need for preventive interventions addressing high neuroticism and low global functioning. Remission in young women was predicted by positive mental health. It may be helpful to include resource-based interventions, which can strengthen or support general positive mental health. Relapse in young women was predicted by two negative psychological factors: high neuroticism and reporting many dysfunctional attitudes. Psychotherapy addressing the characteristics and behaviour of neurotic patients might be beneficial. Interventions should also focus on addressing and changing dysfunctional attitudes. PMID- 27256537 TI - Alcoholic liver disease patients' perspective of a coping and physical activity oriented rehabilitation intervention after hepatic encephalopathy. AB - AIM AND OBJECTIVE: To identify and describe the impact of a coping and physical activity-oriented rehabilitation intervention on alcoholic liver disease patients after hepatic encephalopathy in terms of their interaction with professionals and relatives. BACKGROUND: Patients who have experienced alcohol-induced hepatic encephalopathy have reduced quality of life, multiple complications, and social problems, and rehabilitation opportunities for these patients are limited. DESIGN: A grounded theory study and an evaluation study of a controlled intervention study. METHODS: Semi-structured interviews were conducted with 10 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy and participated in a coping and physical activity-oriented rehabilitation intervention. Richard S. Lazarus's theory of stress and coping inspired the interview guide. RESULTS: The significance of a coping and physical activity oriented rehabilitation intervention on alcoholic liver disease patients' ability to cope with problems after surviving alcohol-induced hepatic encephalopathy in terms of their interaction with professionals and relatives was characterised by the core category 'regain control over the diseased body'. This is subdivided into three separate categories: 'the experience of being physically strong', 'togetherness' and 'self-control', and they impact each other and are mutually interdependent. CONCLUSION: Alcoholic liver disease patients described the strength of the rehabilitation as regaining control over the diseased body. Professionals and relatives of patients with alcoholic liver disease may need to focus on strengthening and preserving patients' control of their diseased body by facilitating the experience of togetherness, self-control and physical strength when interacting with and supporting patients with alcoholic liver disease. RELEVANCE TO CLINICAL PRACTICE: A coping and physical activity-oriented rehabilitation intervention may help alcoholic liver disease patients to regain control over their diseased body and give patients the experience of togetherness, self-control and physical strength. Professionals should be aware of giving the patients the experience of togetherness in their interactions, help them perceive self-control and gain physical strength during their rehabilitation. PMID- 27256538 TI - Subscapularis function after total shoulder arthroplasty: electromyography, ultrasound, and clinical correlation. AB - BACKGROUND: The literature lacks electromyographic (EMG) examination of subscapularis function in the postoperative period after total shoulder arthroplasty (TSA). The primary purpose of this study was to document EMG activity of the subscapularis after TSA and to correlate it with clinical and ultrasound findings. METHODS: The study included 30 patients who were at least 1 year (average, 2.1 years) from surgery, status post TSA approached through a standard subscapularis tenotomy. Patients returned for a physical examination, ultrasound evaluation, and EMG evaluation. Patients also completed postoperative surveys: the American Shoulder and Elbow Surgeons questionnaire, the Simple Shoulder Test, and the 12-Item Short Form Health Survey. RESULTS: The American Shoulder and Elbow Surgeons, Simple Shoulder Test, and physical 12-Item Short Form Health Survey scores improved from preoperatively to postoperatively, respectively, 45.3 to 76.8 (P = .0002), 3.9 to 9.0 (P < .0001), and 33.9 to 42.8 (P = .017). Six patients had a positive lift-off test result, and the belly-press test result was negative in all patients. Two patients had a subscapularis rupture on ultrasound. The postoperative EMG finding was normal in 15 patients; in the other 15 patients, there was evidence of chronic denervation with reinnervation changes: 30% subscapularis, 27% infraspinatus, 20% supraspinatus, 20% teres minor, and 13% rhomboids. CONCLUSIONS: This is the first study using a comparison EMG evaluation to document subscapularis function after TSA. EMG evaluation showed that active denervation of the subscapularis was not evident in any patient at least 1 year after TSA. However, in half of the patients, there was evidence of chronicdenervation and reinnervation changes across 5 muscle groups. We theorize that surgical exposure, traction, and the use of interscalene regional anesthesia may contribute to these unexpected EMG results. PMID- 27256539 TI - The effects of mirror therapy on pain and motor control of phantom limb in amputees: A systematic review. AB - BACKGROUND AND OBJECTIVE: Phantom limb pain (PLP) is a major problem after limb amputation. Mirror therapy (MT) is a non-pharmacological treatment using representations of movement, the efficacy of which in reducing PLP remains to be clarified. Here, we present the first systematic review on MT efficacy in PLP and phantom limb movement (PLM) in amputees (lower or upper limb). METHODS: A search on Medline, Cochrane Database and Embase, crossing the keywords "Phantom Limb" and "Mirror Therapy" found studies which were read and analyzed according the PRISMA statement. RESULTS: Twenty studies were selected, 12 on the subject of MT and PLP, 3 on MT and PLM, 5 on MT and both (PLP and PLM). Among these 20 studies, 5 were randomized controlled trials (163 patients), 6 prospective studies (55 patients), 9 case studies (40 patients) and methodologies were heterogeneous. Seventeen of the 18 studies reported the efficacy of MT on PLP, but with low levels of evidence. One randomized controlled trial did not show any significant effect of MT. As to the effect of MT on PLM, the 8 studies concerned reported effectiveness of MT: 4 with a low level of evidence and 4 with a high level of evidence. An alternative to visual illusion seems to be tactile or auditory stimulation. CONCLUSION: We cannot recommend MT as a first intention treatment in PLP. The level of evidence is insufficient. Further research is needed to assess the effect of MT on pain, prosthesis use, and body representation, and to standardize protocols. PMID- 27256540 TI - Impact of pretransplant minimal residual disease on the post-transplant outcome of pediatric acute lymphoblastic leukemia. AB - There are few reports on the clinical significance of MRD before HSCT in pediatric ALL. We retrospectively analyzed the clinical significance of FCM-based detection of MRD (FCM-MRD) before allogeneic HSCT in pediatric ALL. Of 38 pediatric patients who underwent allogeneic HSCT for the first time between 1998 and 2014, 33 patients were in CR and five patients were in non-CR. The CR group was further divided into two groups based on the pretransplant FCM-MRD level: the MRD(neg) (<0.01%; 30 patients) group and the MRD(pos) (>=0.01%; three patients) group. There were significant differences in the three-yr event-free survival rates between the CR and non-CR group, and between the MRD(neg) and MRD(pos) group. The three-yr cumulative RI in the MRD(neg) group were 27.3% +/- 8.8%, whereas two of the three patients in the MRD(pos) group relapsed within one yr after HSCT. The clinical outcome of the MRD(pos) group was as poor as that of the non-CR group in pediatric ALL. Therefore, an improvement in pretransplant treatment that aims to achieve a more profound remission would contribute to reducing the risk of relapse. PMID- 27256541 TI - In situ TEM tensile testing of carbon-linked graphene oxide nanosheets using a MEMS device. AB - This paper reports in situ transmission electron microscopy (TEM) tensile testing of carbon-linked graphene oxide nanosheets using a monolithic TEM compatible microelectromechanical system device. The set-up allows direct on-chip nanosheet thickness mapping, high resolution electron beam linking of a pre-fractured nanosheet, and mechanical tensile testing of the nanosheet. This technique enables simultaneous mechanical and high energy electron beam characterization of 2D nanomaterials. PMID- 27256542 TI - The CRISPR/Cas9 Genome Editing Revolution. PMID- 27256543 TI - Public readiness for HIV self-testing in Kenya. AB - High interest and a growing body of evidence suggest that HIV self-testing could help fill the HIV testing gap for populations who have been hesitant to access testing services through current mechanisms. Evidence from five of six studies funded by 3ie answers questions posed by the Kenyan government to understand the readiness of Kenyans for HIV self-testing. The findings suggest that Kenyans are generally ready for HIV self-testing. Most people would not only like to obtain self-test kits through public health facilities but also expect to be able to obtain them from pharmacies - easy access being a key factor for a distribution outlet. Respondents across the studies seem to understand the importance of counseling and confirmatory testing, although the decision to access services after an HIV self-test will certainly be influenced by the results of the test. Respondents do have some concerns about potential harms and abuses from HIV self tests. These concerns are focused on what they expect others would do, rather than reflections of what they say they would do themselves. Additionally, most people believe that such concerns were mostly unwarranted and/or could be addressed. PMID- 27256544 TI - Barriers to Parent Support for Physical Activity in Appalachia. AB - BACKGROUND: Parent support for child physical activity is a consistent predictor of increased childhood activity. Little is known about factors that prevent or facilitate support. The purpose of this research was to identify barriers to parent support for child physical activity in Appalachian parents. METHODS: A cross-sectional study assessed parents whose children participated in Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) screenings in a rural Appalachian state. Barriers to parental support for physical activity, demographics, geographic location, and parental support for activity were measured. RESULTS: A total of 475 parents completed surveys. The majority were mothers (86.7%), parents of kindergarteners (49.5%), white (89.3%), and living in a nonrural area (70.5%). Community-level factors were most frequently cited as barriers, particularly those related to the built environment. Rural and low income parents reported significantly higher barriers. Community, interpersonal, and intrapersonal barriers were negatively correlated with parent support for child physical activity. Parents of girls reported a higher percentage of barriers related to safety. CONCLUSIONS: Reported barriers in this sample differed from those reported elsewhere (Davison, 2009). Specific groups such as low-income and rural parents should be targeted in intervention efforts. Future research should explore gender differences in reported barriers to determine the influence of cultural stereotypes. PMID- 27256545 TI - Differential effects of conifer and broadleaf litter inputs on soil organic carbon chemical composition through altered soil microbial community composition. AB - A strategic selection of tree species will shift the type and quality of litter input, and subsequently magnitude and composition of the soil organic carbon (SOC) through soil microbial community. We conducted a manipulative experiment in randomized block design with leaf litter inputs of four native subtropical tree species in a Pinus massoniana plantation in southern China and found that the chemical composition of SOC did not differ significantly among treatments until after 28 months of the experiment. Contrasting leaf litter inputs had significant impacts on the amounts of total microbial, Gram-positive bacterial, and actinomycic PLFAs, but not on the amounts of total bacterial, Gram-negative bacterial, and fungal PLFAs. There were significant differences in alkyl/O-alkyl C in soils among the leaf litter input treatments, but no apparent differences in the proportions of chemical compositions (alkyl, O-alkyl, aromatic, and carbonyl C) in SOC. Soil alkyl/O-alkyl C was significantly related to the amounts of total microbial, and Gram-positive bacterial PLFAs, but not to the chemical compositions of leaf litter. Our findings suggest that changes in forest leaf litter inputs could result in changes in chemical stability of SOC through the altered microbial community composition. PMID- 27256546 TI - Dermal glands in freshwater mites Limnesia undulata (O.F. Muller, 1776) and Limnesia fulgida (C.L. Koch, 1836) (Acariformes, Limnesiidae). AB - Dermal glands in the water mites Limnesia undulata (O.F. Muller, 1776) and Limnesia fulgida (C.L. Koch, 1836) and their secretion were studied by means of light microscopical, transmission electron microscopical (TEM) and scanning electron microscopical (SEM) methods. These mites possess two types of dermal glands - the 'common' dermal glands in a number of 14 pairs and one pair of the so-called 'idiosomal' dermal glands. The common dermal glands are bi-lobed organs and consist of high prismatic secretory cells directed to the gland mouth and mostly replacing the intra-alveolar lumen. The cells contain numerous cisterns of rough endoplasmic reticulum (RER) and specifically organized Golgi bodies (GB) producing electron-dense elongated secretory granules. These granules are released from the cells via apocrine secretion and come to the gland mouth, where they are sometimes accompanied by secretory cell cytoplasm. The final secretion may show a fibrous character. The idiosomal glands are sac-like organs stretched along the ventral body wall in posterior direction from the gland orifice corresponding to the epimeroglandularia 4. The secretory epithelium leaves a large intra-alveolar lumen filled with an electron-dense secretory material. Golgi bodies are organized identically with those in the common glands, which indicates the general homology of these two types of dermal glands. The glands' orifices are organized similarly in all glands and possess an internal funnel shaped sclerite with muscle armament, an internal valve, medial epicuticular flaps and an external circular cuticular ring. All glandularia, except for E4 and V1, are accompanied with a long and thin sensitive seta. During fixation, secretion of the common dermal glands is extruded to the exterior in the form of large amounts of convoluted tube-like structures. In the living organisms, being secreted in mass from the glands, this secretion acquires the form of long rigid mostly hollow un-branched threads comparable with the similar silken threads of other water arthropods. The function of the idiosomal glands secretion still remains unknown. PMID- 27256547 TI - Treatment of insulin resistance by acupuncture: a review of human and animal studies. AB - BACKGROUND: Numerous experimental studies have demonstrated that acupuncture can correct various metabolic disorders such as hyperglycaemia, overweight, hyperphagia, hyperlipidaemia, inflammation, altered activity of the sympathetic nervous system, and insulin signalling defects, all of which contribute to the development of insulin resistance. OBJECTIVE: To review human and animal studies investigating acupuncture as a treatment for insulin resistance, and to evaluate its potential to increase insulin sensitivity. METHODS: PubMed was searched for relevant articles published between January 2008 and October 2015. Search terms used were 'acupuncture', 'insulin resistance', 'insulin sensitivity', and 'blood glucose'. Additional secondary sources of information included reference lists from retrieved papers and pertinent papers identified by hand searches of relevant journals not found in the database. RESULTS: In total, 31 articles were included in this review and comprised studies of the following insulin resistant conditions: obesity (n=9); diabetes mellitus (n=12); polycystic ovarian syndrome (n=7); skeletal muscle atrophy (n=1); ischaemic heart disease (n=1); and fatty liver disease (n=1). Of these articles, seven were human trials and 24 animal experiments. Collectively, the studies suggest that electroacupuncture (EA) at low intensity and low frequency can reduce insulin resistance and increase insulin sensitivity in a range of different insulin-resistant conditions. CONCLUSIONS: EA, used alone or in combination with other therapies, such as Chinese herbs or diet-exercise interventions, has the potential to be an effective treatment for insulin resistance. Additional controlled clinical studies of acupuncture are needed in subjects with diabetes mellitus, ischaemic heart disease, muscle atrophy, and fatty liver disease. PMID- 27256548 TI - Different methods of dentin processing for application in bone tissue engineering: A systematic review. AB - Dentin has become an interesting potential biomaterial for tissue engineering of oral hard tissues. It can be used as a scaffold or as a source of growth factors in bone tissue engineering. Different forms of dentin have been studied for their potential use as bone substitutes. Here, we systematically review different methods of dentin preparation and the efficacy of processed dentin in bone tissue engineering. An electronic search was carried out in PubMed and Scopus databases for articles published from 2000 to 2016. Studies on dentin preparation for application in bone tissue engineering were selected. The initial search yielded a total of 1045 articles, of which 37 were finally selected. Review of studies showed that demineralization was the most commonly used dentin preparation process for use in tissue engineering. Dentin extract, dentin particles (tooth ash), freeze-dried dentin, and denatured dentin are others method of dentin preparation. Based on our literature review, we can conclude that preparation procedure and the size and shape of dentin particles play an important role in its osteoinductive and osteoconductive properties. Standardization of these methods is important to draw a conclusion in this regard. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2616-2627, 2016. PMID- 27256550 TI - Glia: An astrocytic axis. PMID- 27256549 TI - Urological Procedures in Urolithiasis and Their Association with Chronic Kidney Disease. AB - BACKGROUND AND OBJECTIVES: Epidemiological evidence suggests that patients with urolithiasis are at increased risk for end-stage renal disease (ESRD). It is unclear if urological intervention impacts the progression of chronic kidney disease (CKD). METHODS: We conducted a retrospective observational cohort study of patients in the Marshfield Epidemiologic Study Area database between January 1991 and May 2007, where 1,340 patients diagnosed with urolithiasis were extracted. Of the 1,340 subjects, 446 had urological procedures for management of urolithiasis. Those that underwent these procedures were compared to those that did not. Cox proportional hazards models adjusted for age, gender, and comorbidities were performed to evaluate the risk for CKD, elevated serum creatinine, and any-cause mortality. RESULTS: Baseline comorbidities in patients with and without procedures were not significantly different except for obesity (P<0.0001). Subjects that underwent procedures were at increased risk for elevated serum creatinine (Hazard Ratio (HR) [95% CI] =1.49 [1.19-1.85]) when compared to those that did not undergo a urologic procedure during the study period. The results did not reveal a significant difference in incidence of CKD or any-cause mortality. CONCLUSIONS: Patients who undergo urologic procedures are at increased risk for elevated creatinine. Urological procedures do not appear to impact incidence of CKD or mortality and, in fact, may prevent long-term renal dysfunction. PMID- 27256551 TI - Depression: Breaking down ketamine's actions. PMID- 27256554 TI - Neuroendocrinology: Switching on puberty. PMID- 27256552 TI - Over the river, through the woods: cognitive maps in the hippocampus and orbitofrontal cortex. AB - The hippocampus and the orbitofrontal cortex (OFC) both have important roles in cognitive processes such as learning, memory and decision making. Nevertheless, research on the OFC and hippocampus has proceeded largely independently, and little consideration has been given to the importance of interactions between these structures. Here, evidence is reviewed that the hippocampus and OFC encode parallel, but interactive, cognitive 'maps' that capture complex relationships between cues, actions, outcomes and other features of the environment. A better understanding of the interactions between the OFC and hippocampus is important for understanding the neural bases of flexible, goal-directed decision making. PMID- 27256555 TI - Neurodevelopmental disorders: Zika virus causes brain defects in mice. PMID- 27256553 TI - Autophagy in acute brain injury. AB - Autophagy is an evolutionarily ancient mechanism that ensures the lysosomal degradation of old, supernumerary or ectopic cytoplasmic entities. Most eukaryotic cells, including neurons, rely on proficient autophagic responses for the maintenance of homeostasis in response to stress. Accordingly, autophagy mediates neuroprotective effects following some forms of acute brain damage, including methamphetamine intoxication, spinal cord injury and subarachnoid haemorrhage. In some other circumstances, however, the autophagic machinery precipitates a peculiar form of cell death (known as autosis) that contributes to the aetiology of other types of acute brain damage, such as neonatal asphyxia. Here, we dissect the context-specific impact of autophagy on non-infectious acute brain injury, emphasizing the possible therapeutic application of pharmacological activators and inhibitors of this catabolic process for neuroprotection. PMID- 27256557 TI - Techniques: A CRISPR method of localization. PMID- 27256558 TI - Alcohol drinking patterns and risk of functional limitations in two cohorts of older adults. AB - BACKGROUND & AIMS: Several studies have found that moderate alcohol intake is associated with lower risk of functional limitations in older adults. However, no previous investigation has assessed this association in older adults from Mediterranean countries, who show characteristic drinking patterns. METHODS: Data were taken from the UAM and the Seniors-ENRICA cohorts in Spain, comprising community-dwelling people aged >=60 years. At baseline, participants in both cohorts were classified as non-drinkers, ex-drinkers, moderate drinkers and heavy drinkers (the threshold between moderate and heavy intake was >=40 g/day in men and >=24 g/day in women). The Seniors-ENRICA cohort allowed assessment of a Mediterranean Drinking Pattern (MDP), defined as moderate alcohol intake, with wine preference (>=80% of alcohol consumed as wine) and drinking only with meals. The incidence of limitation in mobility, agility, and instrumental activities of daily living (IADL) was ascertained in each cohort at the end of a 3.5-year follow-up. Analyses were adjusted for sex, age, education, lifestyle, BMI, chronic conditions, and functional limitations at baseline others than the studied limitation. RESULTS: Compared with non-drinkers, ex-drinkers showed a higher risk of IADL limitation (pooled adjusted odds ratio [paOR]: 1.63; 95% confidence interval [CI]: 1.04-2.21). By contrast, moderate drinkers had a lower risk of limitations in mobility (paOR: 0.80; 95% CI: 0.63-0.97), agility (paOR: 0.82; 95% CI: 0.65-0.99) and IADL (paOR: 0.54; 95% CI: 0.39-0.69). Among individuals reporting poor or fair health, the MDP was associated with lower risk of mobility limitation (aOR: 0.51; 95% CI: 0.27-0.97). CONCLUSION: In older adults, moderate alcohol consumption, as well as the MDP in specific subgroups, is associated with lower risk of functional limitation. These results should not serve to promote alcohol intake, because older adults are particularly vulnerable to its harmful effects. PMID- 27256556 TI - Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. AB - The dopamine system is unique among the brain's modulatory systems in that it has discrete projections to specific brain regions involved in motor behaviour, cognition and emotion. Dopamine neurons exhibit several activity patterns - including tonic and phasic firing - that are determined by a combination of endogenous pacemaker conductances and regulation by multiple afferent systems. Emerging evidence suggests that disruptions in these regulatory systems may underlie the pathophysiology of several psychiatric disorders, including schizophrenia and depression. PMID- 27256559 TI - Impact of decreasing energy intakes in major burn patients: A 15-year retrospective cohort study. AB - BACKGROUND & AIMS: Nutritional therapy is particularly important after major burn injury and specific nutritional guidelines have been developed. The study aimed at evaluating the impact of the changes in our nutritional practice, general compliance with the guidelines and potential consequences. METHODS: Retrospective analysis of prospectively collected data in burn patients requiring intensive care (ICU) between 1999 and 2014. INCLUSION CRITERIA: admission on day 1, full treatment and length of ICU stay >7 days. Four periods (P) were defined by protocol changes (P1: 1999-2001, P2: 2002-2005, P3: 2006-2010, P4: 2011-2014). Collected data: demographic and nutritional data, infectious complications, weights, CRP and prealbumin concentrations during the first 21 days. RESULTS: 240 patients were included (median age 43 years, burned area 25%). Measured energy expenditure (MEE) was stable through all periods but the prescribed caloric target decreased significantly, and below MEE (P1: 33 kcal/kg, IQR 7, P4: 28 kcal/kg, IQR 8, p < 0.001). Energy delivery ended decreasing below 30 kcal/kg/day (P1: 30 kcal/kg, IQR 23, P4: 25 kcal/kg, IQR 12, p < 0.001). Protein intakes increased due the use of high protein solutions and glutamine (P1: 1.04 g/kg, IQR 0.90, P4: 1.26, IQR 0.99, p < 0.001). Weight loss by day 21 increased significantly according to area under the curve (P1: 701, IQR 38, P2: 722, IQR 51, P4: 689 IQR 63, p = 0.02). Prealbumin levels decreased with energy decrease (P1: 150 mg/L, IQR 110, P4: 80 mg/L, IQR 70, p = 0.003). CONCLUSIONS: The observed reduction of the energy delivery <30 kcal/kg was associated with a supplemental weight loss and lower prealbumin concentrations. PMID- 27256560 TI - Three new alkaloids from the seeds of Nigella glandulifera. AB - Three new alkaloids namely 8-(4-hydroxyphenyl)-6-methoxy-3,4-dihydroisoquinolin 1(2H)-one (1), 4-aminonigellidine (2), and N-[(4-hydroxy-2-isopropyl-5 methyl)]phenylurea (3), along with six known ones (4-9), were isolated from the seeds of Nigella glandulifera. The structures of 1-3 were determined through spectroscopic analyses (HRESIMS, 1D/2D NMR). Compound 1 was a rare isoquinolinone alkaloid with phenyl substituted at C-8. PMID- 27256561 TI - The Influence of the Degree of Rurality on EMR Adoption, by Physician Specialty. AB - OBJECTIVE: To explore the influence of varying degrees of remoteness on practice level electronic medical record (EMR) adoption, including whether the effect differs across practice specialty. DATA SOURCES: Survey data on over 270,000 office-based physician practices (representing over 1,250,000 providers) collected by SK&A information services during 2012. STUDY DESIGN: This study examined differences in EMR adoption by practices located across the nine category rural-urban continuum. Logistic regressions and associated marginal effects are used to assess how much a move up or down the rural-urban continuum code impacts the likelihood of EMR adoption, after controlling for characteristics likely to affect EMR adoption such as practice size and specialty. PRINCIPAL FINDINGS: Overall practice-level EMR adoption rates generally increase with the degree of rurality and range from 47 percent in the most urban counties to over 60 percent in the most rural. Moving from the most urban county to the most rural corresponded to a 7 percent increase in the likelihood of EMR adoption (p < .01). CONCLUSIONS: EMR adoption rates do vary significantly across nonmetropolitan counties, and they generally increase as a practice becomes more rural. From a policy perspective, this suggests that urban practices may in fact be the lowest hanging remaining fruit for increasing EMR adoption rates. PMID- 27256562 TI - Consumers' practical understanding of healthy food choices: a fake food experiment. AB - Little is known about laypeople's practical understanding of a healthy diet, although this is important to successfully promote healthy eating. The present study is the first to experimentally examine how consumers define healthy and balanced food choices for an entire day compared with normal choices and compared with dietary guidelines. We used an extensive fake food buffet (FFB) with 179 foods commonly consumed in the Swiss diet. The FFB is a validated method to investigate food choice behaviour in a well-controlled laboratory setting. People from the general population in Switzerland (n 187; 51.9 % females), aged between 18 and 65 years, were randomly assigned to one of two conditions. In the control group, the participants were instructed to serve themselves foods they would eat on a normal day, whereas in the 'healthy' group they were instructed to choose foods representing a healthy diet. Participants chose significantly more healthy foods, with 4.5 g more dietary fibre, 2 % more protein and 2 % less SFA in the 'healthy' group compared with the control group. However, in both experimental conditions, participants served themselves foods containing twice as much sugar and salt than recommended by dietary guidelines. The results suggest that laypeople lack knowledge about the recommended portion sizes and the amounts of critical nutrients in processed food, which has important implications for communicating dietary guidelines. Furthermore, the energy of the food served was substantially correlated with the energy needs of the participants, demonstrating the potential of the fake food buffet method. PMID- 27256564 TI - DNA Methylation in Cancer and Aging. AB - DNA methylation is known to be abnormal in all forms of cancer, but it is not really understood how this occurs and what is its role in tumorigenesis. In this review, we take a wide view of this problem by analyzing the strategies involved in setting up normal DNA methylation patterns and understanding how this stable epigenetic mark works to prevent gene activation during development. Aberrant DNA methylation in cancer can be generated either prior to or following cell transformation through mutations. Increasing evidence suggests, however, that most methylation changes are generated in a programmed manner and occur in a subpopulation of tissue cells during normal aging, probably predisposing them for tumorigenesis. It is likely that this methylation contributes to the tumor state by inhibiting the plasticity of cell differentiation processes. Cancer Res; 76(12); 3446-50. (c)2016 AACR. PMID- 27256563 TI - Proteasome Addiction Defined in Ewing Sarcoma Is Effectively Targeted by a Novel Class of 19S Proteasome Inhibitors. AB - Ewing sarcoma is a primitive round cell sarcoma with a peak incidence in adolescence that is driven by a chimeric oncogene created from the fusion of the EWSR1 gene with a member of the ETS family of genes. Patients with metastatic and recurrent disease have dismal outcomes and need better therapeutic options. We screened a library of 309,989 chemical compounds for growth inhibition of Ewing sarcoma cells to provide the basis for the development of novel therapies and to discover vulnerable pathways that might broaden our understanding of the pathobiology of this aggressive sarcoma. This screening campaign identified a class of benzyl-4-piperidone compounds that selectively inhibit the growth of Ewing sarcoma cell lines by inducing apoptosis. These agents disrupt 19S proteasome function through inhibition of the deubiquitinating enzymes USP14 and UCHL5. Functional genomic data from a genome-wide shRNA screen in Ewing sarcoma cells also identified the proteasome as a node of vulnerability in Ewing sarcoma cells, providing orthologous confirmation of the chemical screen findings. Furthermore, shRNA-mediated silencing of USP14 or UCHL5 in Ewing sarcoma cells produced significant growth inhibition. Finally, treatment of a xenograft mouse model of Ewing sarcoma with VLX1570, a benzyl-4-piperidone compound derivative currently in clinical trials for relapsed multiple myeloma, significantly inhibited in vivo tumor growth. Overall, our results offer a preclinical proof of concept for the use of 19S proteasome inhibitors as a novel therapeutic strategy for Ewing sarcoma. Cancer Res; 76(15); 4525-34. (c)2016 AACR. PMID- 27256565 TI - Depletion of CD4+ CD25+ regulatory T cells confers susceptibility to experimental autoimmune encephalomyelitis (EAE) in GM-CSF-deficient Csf2-/- mice. AB - Previous studies established that GM-CSF-deficient (Csf2-deficient) mice exhibit profound resistance to experimental autoimmune encephalomyelitis. This study addressed whether the resistance of Csf2-deficient mice was a result of a requirement for GM-CSF in controlling the functional balance between effector and regulatory T cell subsets during experimental autoimmune encephalomyelitis. The main observation was that treatment with the anti-CD25 mAb PC61 rendered Csf2 deficient mice fully susceptible to severe, chronic experimental autoimmune encephalomyelitis, with disease incidences and severities equivalent to that of C57BL/6 mice. When both donors and recipients were treated with PC61 in a passive model of experimental autoimmune encephalomyelitis, adoptive transfer of myelin specific Csf2-deficient T cells into Csf2-deficient recipients resulted in a nonresolving chronic course of severe paralytic experimental autoimmune encephalomyelitis. The peripheral Csf2-deficient T cell repertoire was marked by elevated CD3+ T cell frequencies that reflected substantial accumulations of naive CD44null-low CD4+ and CD8+ T cells but essentially normal frequencies of CD4+ CD25+ forkhead box P3+ T cells among the CD3+ T cell pool. These findings suggested that Csf2-deficient mice had secondary deficiencies in peripheral T cell sensitization to environmental antigens. In accordance, myelin oligodendrocyte glycoprotein 35-55/CFA-sensitized Csf2-deficient mice exhibited deficient peripheral sensitization to myelin oligodendrocyte glycoprotein, whereas pretreatment of Csf2-deficient mice with PC61 enabled the robust induction of myelin oligodendrocyte glycoprotein-specific T cell responses in the draining lymphatics. In conclusion, the experimental autoimmune encephalomyelitis resistance of Csf2-deficient mice, at least in part, reflects a deficient induction of effector T cell function that cannot surmount normal regulatory T cell barriers. Experimental autoimmune encephalomyelitis effector responses, however, are unleashed upon depletion of regulatory CD25+ T cells. PMID- 27256566 TI - mTOR inhibition potentiates cytotoxicity of Vgamma4 gammadelta T cells via up regulating NKG2D and TNF-alpha. AB - gammadelta T cells play a critical role in early anti-tumor immunity and perform cytotoxicity via NKG2D for recognition and multiple cytotoxic factors for tumor killing. Recent studies have demonstrated pivotal roles of mTOR-mediated metabolism in the maturation, differentiation, and effector function of diverse immune cells, including DCs, NK cells, CD4+ T cell subsets, and CD8+ T cells, but the role of mTOR signaling in gammadelta T cells is barely known. Here, we showed that suppressing mTOR signaling in in vitro-expanded Vgamma4 gammadelta T cells via the mechanistic inhibitor rapamycin enhanced their cytotoxicity against multiple tumor cell lines, and these cells performed better tumor-suppressing effects upon adoptive therapy. Further investigation revealed that elevated cytotoxicity was a result of up-regulation of NKG2D and TNF-alpha. Moreover, rapamycin treatment significantly decreased the expression of CISH and increased pSTAT5. The inhibition of STAT5 pathways via siRNA interference or a specific inhibitor eliminated the up-regulation of NKG2D and TNF-alpha in rapamycin treated Vgamma4 gammadelta T cells. These results uncovered an important role of mTOR signaling in the cytotoxic effector function of gammadelta T cells and provided a potential strategy to improve gammadelta T cell-based cancer immunotherapy. PMID- 27256568 TI - Oxidized phosphatidylcholine induces the activation of NLRP3 inflammasome in macrophages. AB - The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein complex consisting of a receptor, an adaptor protein, and procaspase 1 that induces the secretion of the mature form of IL-1beta in response to microbial infection and danger signals. Activation of the NLRP3 inflammasome induced by endogenous danger signal molecules is closely linked to the development and progress of chronic inflammatory diseases. The oxidation of phospholipids occurs upon cellular stress and damage, resulting in the accumulation of oxidized phosphatidylcholines (oxPAPC) such as 1-palmitoyl-2-(5 oxovaleroyl)-sn-glycero-phosphocholine (POVPC) at inflammatory sites. In this study, we investigated whether oxidized phosphatidylcholine induces the activation of NLRP3 inflammasome in macrophages, leading to the secretion of IL 1beta. POVPC induced the degradation of procaspase-1 to caspase-1(p10), the cleavage of pro-IL-1beta to IL-1beta, and oligomerization of ASC in primary mouse bone marrow-derived macrophages. POVPC-induced production of caspase-1, and IL 1beta was abolished in macrophages derived from NLRP3- or caspase-1-deficient mice. In an air pouch model and a peritonitis model in mice, POVPC injection resulted in the production of caspase-1(p10), IL-1beta, and IL-18 in wild-type, but not in NLRP3-deficient, mice. POVPC-induced inflammasome activation was mediated by mitochondrial reactive oxygen species resulting from intracellular Ca2+ signaling and mitochondrial destabilization. Our results demonstrate that endogenously produced oxidized phosphatidylcholines such as POVPC induce the activation of NLRP3 inflammasome, leading to the production of IL-1beta in macrophages. The results provide an insight to understand how the oxidized lipids endogenously produced upon cellular stress and tissue damage contribute to the inflammatory reaction at pathologic sites. PMID- 27256567 TI - Effects of alcohol withdrawal on monocyte subset defects in chronic alcohol users. AB - Excessive alcohol consumption has a modulating effect on immune functions that may contribute to decreased immunity and host defense. It is associated with increased intestinal permeability to endotoxins that is normalized after 14 d of abstinence. Whether and how blood monocyte subsets are impaired in patients with an AUD and what their evolution is after alcohol withdrawal are the paper's objectives. With the use of flow cytometry, blood monocyte subsets were quantified in AUDs before (n = 40) and 2 wk after (n = 33) alcohol withdrawal and compared with HC donors (n = 20). Expression of TLR2 and TLR4 on monocyte subsets was also quantified. Cytokine response of monocytes was monitored following PGN and LPS stimulation. The CD14+CD16- subset was decreased, whereas the CD14dimCD16+ subset was expanded (P < 0.001) in AUD compared with HC. The frequencies of TLR2- and TLR4-expressing monocytes were reduced in AUD compared with HC. Although the basal production of IL-1, IL-6, and TNF by monocytes in AUD was compared with HC, the PGN- and LPS-mediated IL-6 and TNF production was increased in AUD. Frequencies of IL-6-expressing monocytes were higher in AUD than HC. Alcohol withdrawal partially restored the distribution of monocyte subsets and the frequency of IL-6-producing monocytes and increased the frequency of TNF-producing cells in response to LPS and PGN stimulation to levels compared with those in HC. Our findings indicate that chronic alcohol use alters the distribution as well as the phenotypic and functional characteristics of blood monocyte subsets, which are partially restored following 2 wk of alcohol withdrawal. PMID- 27256569 TI - AQP8 transports NOX2-generated H2O2 across the plasma membrane to promote signaling in B cells. AB - H2O2 acts as a second messenger in key signaling circuits, transiently modulating tyrosine phosphatases and kinases. We investigated its origin, membrane transport, and functional role during B cell activation and differentiation. Our data identified NADPH-oxidase 2 as the main source of H2O2 and aquaporin 8 as a transport facilitator across the plasma membrane. On aquaporin 8 silencing, inducible B lymphoma cells responded poorly to TLR and BCR stimulation. Their differentiation was severely impaired, as demonstrated by retarded onset of IgM polymerization, low amounts of IgM secretion, and prolonged BCR expression on the cell surface. A silencing-resistant aquaporin 8 rescued responsiveness, confirming that the import of H2O2 across the membrane is essential for B cell activation. The addition of exogenous catalase to primary B splenocytes severely impaired the tyrosine phosphorylation induced by BCR cross-linking, as did the absence of NOX2 in a murine model of chronic granulomatous disease. Importantly, re-expression of gp91phox through gene therapy restored the specific B cell signaling deficiency in NOX2-/- cells. Thus, efficient induction of B cell activation and differentiation requires intact H2O2 fluxes across the plasma membrane for signal amplification. PMID- 27256570 TI - Combinatorial approach to cancer immunotherapy: strength in numbers. AB - Immune-checkpoint blockade therapy with antibodies targeting CTLA-4 and PD-1 has revolutionized melanoma treatment by eliciting responses that can be remarkably durable and is now advancing to other malignancies. However, not all patients respond to immune-checkpoint inhibitors. Extensive preclinical evidence suggests that combining immune-checkpoint inhibitors with other anti-cancer treatments can greatly improve the therapeutic benefit. The first clinical success of the combinatorial approach to cancer immunotherapy was demonstrated using a dual checkpoint blockade with CTLA-4 and PD-1 inhibitors, which resulted in accelerated FDA approval of this therapeutic regimen. In this review, we discuss the combinations of current and emerging immunotherapeutic agents in clinical and preclinical development and summarize the insights into potential mechanisms of synergistic anti-tumor activity gained from animal studies. These promising combinatorial partners for the immune-checkpoint blockade include therapeutics targeting additional inhibitory receptors of T cells, such as TIM-3, LAG-3, TIGIT, and BTLA, and agonists of T cell costimulatory receptors 4-1BB, OX40, and GITR, as well as agents that promote cancer cell recognition by the immune system, such as tumor vaccines, IDO inhibitors, and agonists of the CD40 receptor of APCs. We also review the therapeutic potential of regimens combining the immune-checkpoint blockade with therapeutic interventions that have been shown to enhance immunogenicity of cancer cells, including oncolytic viruses, RT, epigenetic therapy, and senescence-inducing therapy. PMID- 27256571 TI - Anti-JAM-C therapy eliminates tumor engraftment in a xenograft model of mantle cell lymphoma. AB - Junctional adhesion molecule (JAM)-C is a member of the JAM family, expressed by a variety of different cell types, including human B lymphocytes and some B-cell lymphoma subtypes-in particular, mantle cell lymphoma (MCL). Treatment with anti JAM-C pAbs reduces homing of human B cells to lymphoid organs in a NOD/SCID mouse model. In the present study, the role of JAM-C in the engraftment of human lymphoma B cells in mice was investigated. Administration of novel anti-JAM-C mAbs reduced tumor growth of JAM-C+ MCL cells in bone marrow, spleen, liver, and lymph nodes of mice. Treatment with anti-JAM-C antibodies significantly reduced the proliferation of JAM-C-expressing lymphoma B cells. Moreover, the binding of anti-JAM-C antibodies inhibited the phosphorylation of ERK1/2, without affecting other signaling pathways. The results identify for the first time the intracellular MAPK cascade as the JAM-C-driven signaling pathway in JAM-C+ B cells. Targeting JAM-C could constitute a new therapeutic strategy reducing lymphoma B-cell proliferation and their capacity to reach supportive lymphoid microenvironments. PMID- 27256572 TI - Functional role of mucosal-associated invariant T cells in HIV infection. AB - MAIT cells represent an evolutionarily conserved, MR1-restricted, innate-like cell subset that express high levels of CD161; have a canonical semi-invariant TCR iValpha7.2; and may have an important role in mucosal immunity against various bacterial and fungal pathogens. Mature MAIT cells are CD161(hi)PLZF(hi)IL 18Ralpha(+)iValpha7.2(+)gammadelta-CD3(+)CD8(+) T cells and occur in the peripheral blood, liver, and mucosa of humans. MAIT cells are activated by a metabolic precursor of riboflavin synthesis presented by MR1 and, therefore, respond to many bacteria and some fungi. Despite their broad antibacterial properties, their functional role in persistent viral infections is poorly understood. Although there is an increasing line of evidence portraying the depletion of MAIT cells in HIV disease, the magnitude and the potential mechanisms underlying such depletion remain unclear. Recent studies suggest that MAIT cells are vulnerable to immune exhaustion as a consequence of HIV and hepatitis C virus infections and HIV/tuberculosis coinfections. HIV infection also appears to cause functional depletion of MAIT cells resulting from abnormal expression of T-bet and EOMES, and effective ART is unable to completely salvage functional MAIT cell loss. Depletion and exhaustion of peripheral MAIT cells may affect mucosal immunity and could increase susceptibility to opportunistic infections during HIV infection. Here, we review some of the important mechanisms associated with depletion and functional loss of MAIT cells and also suggest potential immunotherapeutic strategies to restore MAIT cell functions, including the use of IL-7 to restore effector functions in HIV disease. PMID- 27256573 TI - Galectin-12 inhibits granulocytic differentiation of human NB4 promyelocytic leukemia cells while promoting lipogenesis. AB - As a member of the galectin family of animal lectins, galectin-12 is preferentially expressed in adipocytes and leukocytes. In adipocytes, galectin-12 is associated with lipid droplets and regulates lipid metabolism and energy balance, whereas its role in leukocytes is not clear. Analysis of galectin-12 expression in a public data set of acute myeloid leukemia (AML) samples revealed that it is selectively overexpressed in the M3 subtype, which is also known as acute promyelocytic leukemia (APL). To investigate the role of galectin-12 in APL cells, we manipulated its expression in the APL cell line, NB4, and measured resultant effects on all-trans-retinoic acid (ATRA)-induced granulocytic differentiation. With a doxycycline-inducible gene knockdown system, we found that suppression of galectin-12 promoted ATRA-induced neutrophil differentiation but inhibited lipid droplet formation. Our results indicate that overexpression of galectin-12 contributes to a differentiation block in APL cells, and suppression of galectin-12 facilitates granulocytic differentiation. Furthermore, these data suggest that lipogenesis and other aspects of myeloid differentiation can be differentially regulated. Taken together, these findings suggest that galectin-12 may be a target for treatment of the ATRA-resistant subset of APL. PMID- 27256574 TI - Expression of human gene coding RORgammaT receptor depends on the Sp2 transcription factor. AB - Th17 cells are involved in the immune response against pathogens, autoimmunity, and tumor progression. The differentiation of human Th17 cells requires the upregulation of RORgammaT, which in human cells is still not well understood. We identified 2 putative binding motifs for specificity protein transcription factors from the specificity protein/Kruppel-like factor family in the promoter of human RORgammaT and investigated the involvement of specificity proteins in the transcriptional regulation of this gene. To this end, a human lymphocytic cell line and in vitro-differentiated Th17 cells were used in promoter activity assays, in situ mutagenesis, chromatin immunoprecipitation, and real-time RT-PCR assays. In some experiments, specificity protein expression and activity was inhibited by siRNA and mithramycin A. The results showed that the transcription factor specificity protein 2 recognized binding motifs in the human RORgammaT promoter, which was critical for maintaining expression. Furthermore, specificity protein 2 was necessary for maximum IL-17 expression in in vitro-differentiated Th17 cells. These observations demonstrate the significant role of specificity protein 2 in the regulation of the Th17 signature transcription factor RORgammaT and the maintenance of the Th17 phenotype. The findings also suggest that specificity protein 2 plays a role in Th17-dependent physiologic and pathologic immune responses and might serve as a potential novel target for their modulation. PMID- 27256575 TI - Reach and representativeness of ethnic minority women in the Health Is Power Study: a longitudinal analysis. AB - Reach is a key factor in translating research to practical application. This study examined reach and representativeness of a multi-city, randomized controlled community health trial in African American (AA) and Hispanic or Latina (HL) women. Participants completed measures of demographics, body mass index (BMI), percent body fat, resting heart rate, and blood pressure followed by a run in procedure and a randomization meeting. AA were more likely to be screened out initially; HL were more likely to drop out. Participation did not differ by city or recruitment method. Women who completed the post-intervention assessment were more likely to be AA, older, and have higher socioeconomic status (p values < .05). This study showed moderate levels of reach but overrepresented higher educated, wealthier, and older women at the completion of the study. Representativeness can change over the course of the study and impact the practicality of translating research to practice. PMID- 27256576 TI - Physical activity: a synopsis and comment on "community-wide interventions for increasing physical activity". AB - In this synopsis, we summarize and comment on Baker and colleagues' Cochrane review of studies on the population-level impact of community-wide physical activity (PA) interventions. Insufficient PA remains a major public health problem. Community-wide interventions offer an opportunity to extend reach by increasing the proportion of the population experiencing the intervention. A previous Cochrane review of community-wide PA interventions concluded that evidence for effectiveness was mixed. Hence, Baker and colleagues incorporated new data about community-based PA interventions. This Cochrane review concluded there is an overall lack of evidence that community-wide interventions improve PA outcomes at the population level. Recommendations are that future research should use high quality research design, more explicitly test ways to increase reach, and utilize objective measurements of PA to increase validity. We suggest that future research should first optimize the intervention by systematically evaluating treatment components and selecting a maximally efficient and effective treatment package. PMID- 27256577 TI - Management of chronic visceral pain. AB - Despite marked differences in underlying pathophysiology, the current management of visceral pain largely follows the guidelines derived from the somatic pain literature. The effective management of patients with chronic visceral pain should be multifaceted, including both pharmacological and psychological interventions, thereby providing a mechanism-orientated approach to treatment. Patients can frequently become disenfranchised, and subsequently disengaged, with healthcare providers leading to repeated consultations. Thus, a key aspect of management is to break this cycle by validating patients' symptoms, adopting an empathic approach and taking time to educate patients. To optimize treatment and outcomes in chronic visceral pain we need to move away from approaches exclusively based on dealing with peripheral nociceptive input toward more holistic strategies, taking into account alterations in central pain processing. PMID- 27256578 TI - Teledermoscopy for skin cancer screening. PMID- 27256580 TI - Neurocognitive and Behavioural Outcomes Following Intervention for Obstructive Sleep Apnoea Syndrome in Children. AB - The obstructive sleep apnoea syndrome (OSAS) is common in children and results in several complications when untreated. Considering that children are undergoing important brain development, recent research has focused on neurocognitive and behavioural (NCB) complications of OSAS. Studies have shown that treatment of paediatric OSAS may improve a child's long-term cognitive and social potential and school performance. There is demonstrated benefit in terms of behaviour, attention, and social interactions, as well as likely improvement in cognitive abilities with academic and social achievements. PMID- 27256579 TI - Establishing a rat model for the study of vitamin K deficiency. AB - The main vitamin K-deficient model, minidose warfarin, is different from the pathological mechanism of vitamin K deficiency, which is a shortage of vitamin K. The objective of this study was to establish a new method of vitamin K-deficient model combining a vitamin K-deficient diet with the intragastrical administration of gentamicin in rats. The clotting was assayed by an automated coagulation analyser. The plasma PIVKA-II was assayed by ELISA. The vitamin K status was detected by an HPLC-fluorescence system. In the diet- and gentamicin-induced vitamin K-deficient 14-day group, the rats had undetected vitamin K1 and vitamin K2 in the liver and a prolonged APTT. In the 21-day group, there was also a prolonged PT and a decrease of the FIX activities. In the 28-day group, the undetected vitamin K1 and vitamin K2, the prolonged PT and APTT, and the decrease of the FII, FVII, FIX, and FX activities prompted the suggestion that there were serious deficiencies of vitamin K and vitamin K-dependent coagulation in rats. It is suggested that the diet- and gentamicin-induced vitamin K-deficient 14-day or 21-day model can be used for studies related to the status of vitamin K. The vitamin K-deficient 28-day model can be applied to research involving both the status of vitamin K and of vitamin K-dependent coagulation. In conclusion, the combination of a vitamin K-deficient diet with the administration of gentamicin results in a useful model of vitamin K-deficieny. PMID- 27256581 TI - Identification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis. AB - We use whole genome sequence data and rare variant analysis methods to investigate a subset of the human serum metabolome, including 16 carnitine related metabolites that are important components of mammalian energy metabolism. Medium pass sequence data consisting of 12,820,347 rare variants and serum metabolomics data were available on 1,456 individuals. By applying a penalization method, we identified two genes FGF8 and MDGA2 with significant effects on lysine and cis-4-decenoylcarnitine, respectively, using Delta-AIC and likelihood ratio test statistics. Single variant analyses in these regions did not identify a single low-frequency variant (minor allele count > 3) responsible for the underlying signal. The results demonstrate the utility of whole genome sequence and innovative analyses for identifying candidate regions influencing complex phenotypes. PMID- 27256582 TI - Construction and characterization of a BAC library for functional genomics in Xenopus tropicalis. AB - Large insert genomic DNA libraries are useful resources for genomic studies. Although the genome of Xenopus tropicalis stands as the amphibian reference genome because it benefitted from large-scale sequencing studies, physical mapping resources such as BAC libraries are lagging behind. Here we present the construction and characterization of a BAC library that covers the whole X. tropicalis genome. We prepared this BAC library from the genomic DNA of X. tropicalis females of the Adiopodoume strain. We characterized BAC clones by screening for specific loci, by chromosomal localization using FISH and by systematic BAC end sequencing. The median insert size is about 110kbp and the library coverage is around six genome equivalents. We obtained a total of 163,787 BAC end sequences with mate pairs for 77,711 BAC clones. We mapped all BAC end sequences to the reference X. tropicalis genome assembly to enable the identification of BAC clones covering specific loci. Overall, this BAC library resource complements the knowledge of the X. tropicalis genome and should further promote its use as a reference genome for developmental biology studies and amphibian comparative genomics. PMID- 27256584 TI - In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candida albicans and Cryptococcus neoformans. AB - With the increasing prevalence of fungal infections coupled with emerging drug resistance, there is an urgent need for new and effective antifungal agents. Here we report the antifungal activities of 19 diverse halogenated quinoline (HQ) small molecules against Candida albicans and Cryptococcus neoformans. Four HQ analogues inhibited C. albicans growth with a minimum inhibitory concentration (MIC) of 100 nM, whilst 16 analogues effectively inhibited C. neoformans at MICs of 50-780 nM. Remarkably, two HQ analogues eradicated mature C. albicans and C. neoformans biofilms [minimum biofilm eradication concentration (MBEC) = 6.25-62.5 uM]. Several active HQs were found to penetrate into fungal cells, whilst one inactive analogue was unable to, suggesting that HQs elicit their antifungal activities through an intracellular mode of action. HQs are a promising class of small molecules that may be useful in future antifungal treatments. PMID- 27256583 TI - Resveratrol suppressed seizures by attenuating IL-1beta, IL1-Ra, IL-6, and TNF alpha in the hippocampus and cortex of kindled mice. AB - OBJECTIVE: There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and one third of the patients remain refractory to the disease. Hence, the present study was conducted to evaluate the effects of Resveratrol (RESV) on epileptogenesis in pentylenetetrazole (PTZ)-induced kindling in mice. METHOD: Swiss albino mice were administered RESV (10, 20 and 40 mg/kg,p.o) in acute study. On the seventh day animals were subjected to various neurological and neurobehavioral tests viz, Increasing Current Electroshock Test (ICES), PTZ-induced seizures, passive avoidance response, and elevated plus maze test. For the development of kindling PTZ was administered in a dose of 25 mg/kg, i.p. on every alternate day and RESV in all the three doses was administered daily. Seizure score was continuously monitored till the development of kindling and cognition tests were performed in the end of the study. The animals were sacrificed and levels of inflammatory biomarkers viz., IL-1beta, interleukin-1 receptor antagonist (IL1-Ra), IL-6, and TNF-alpha were assessed in the hippocampus and cortex of the kindled animals. RESULTS: RESV in all three doses increased the seizure threshold to hind limb extension in the ICES test. RESV in all the tested doses suppressed the development of kindling and reduced the levels of IL-1beta, IL1-Ra, IL-6, and TNF alpha in kindled mice. CONCLUSION: RESV suppressed the development of kindling in mice and decreased the levels of inflammatory biomarkers in their hippocampus. RESV modified brain inflammation during epileptogenesis and found to possess nootropic activity in the kindled mice. PMID- 27256585 TI - Molecular mechanisms of membrane impermeability in clinical isolates of Enterobacteriaceae exposed to imipenem selective pressure. AB - Intrinsic mechanisms leading to carbapenem-induced membrane impermeability and multidrug resistance are poorly understood in clinical isolates of Enterobacteriaceae. In this study, molecular behaviours during the establishment of membrane impermeability in members of the Enterobacteriaceae family under imipenem selective pressure were investigated. Clinical isolates (n = 22) exhibiting susceptibility to multiple antibiotics or characterised as extended spectrum beta-lactamase (ESBL)- or AmpC-producers were submitted to progressive passages on Mueller-Hinton agar plates containing subclinical concentrations of imipenem [0.5 * the minimum inhibitory concentration (MIC)]. Changes in outer membrane permeability were evaluated by determination of antimicrobial MICs, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and gene expression analysis related to membrane permeability (i.e. omp35-like, omp36-like and acrA) and regulatory mechanisms (i.e. marA and ompR) by quantitative reverse transcription PCR. Following imipenem induction, 73% of isolates showed increased carbapenem MICs by >=2 doubling dilutions. At an early stage of treatment, imipenem modulated the expression of porins and efflux pump genes, represented by a reduction of 78% in omp36-like and a two-fold increase in acrA expression. Transcriptional factors marA and ompR were also affected by imipenem induction, increasing mRNA expression by 14- and 4-fold, respectively. High marA expression levels were associated with higher values of acrA expression. These results suggest that imipenem is an important factor in the development of an adaptive response to carbapenems by regulating key genes involved in the control of efflux pumps and porins, which could lead to a multidrug-resistant profile in clinical isolates, contributing to possible treatment failure. PMID- 27256586 TI - Current perspectives on tigecycline resistance in Enterobacteriaceae: susceptibility testing issues and mechanisms of resistance. AB - During the past decades, rates of multidrug-resistant (MDR) and carbapenem resistant (CR) Enterobacteriaceae clinical isolates, mainly Klebsiella spp., Escherichia coli, Enterobacter spp., Proteus spp. and Serratia marcescens, have increased, considerably restricting effective antimicrobial treatments. Tigecycline, the first member of the glycylcyclines, has been approved by the US Food and Drug Administration (FDA) for the treatment of complicated skin and soft tissue, complicated intra-abdominal and community-acquired bacterial respiratory infections and is increasingly administered against MDR Enterobacteriaceae. Although resistance has gradually appeared, tigecycline still remains relatively active among Enterobacteriaceae, with resistance rates largely <10% in most wide scale surveillance studies. Tigecycline resistance has been reported in some studies to be elevated among extended-spectrum beta-lactamase (ESBL)-producing, MDR, extensively drug-resistant and CR isolates. Broth microdilution (BMD) is the reference method for tigecycline susceptibility testing, but disagreements have been reported between the methods applied for routine tigecycline susceptibility testing. Therefore, confirmation of daily tigecycline susceptibility testing with BMD appears important in order to avoid misclassification of isolates. Various mechanisms have been reported to confer tigecycline resistance, with RND-type transporters, mainly the AcrAB efflux pump, playing an important role. Other pumps and various control pathways are also implicated in tigecycline resistance. Overall, tigecycline is a potent therapeutic option for enterobacterial infections. Accurate detection of tigecycline susceptibility status and surveillance of resistant organisms in the hospital environment is necessary in order to optimise its use and to preserve tigecycline in our therapeutic arsenal. PMID- 27256587 TI - How antigen specificity directs regulatory T-cell function: self, foreign and engineered specificity. AB - Regulatory T cells (Tregs) are a suppressive subset of T cells that have important roles in maintaining self-tolerance and preventing immunopathology. The T-cell receptor (TCR) and its antigen specificity play a dominant role in the differentiation of cells to a Treg fate, either in the thymus or in the periphery. This review focuses on the effects of the TCR and its antigen specificity on Treg biology. The role of Tregs with specificity for self-antigen has primarily been studied in the context of autoimmune disease, although recent studies have focused on their role in steady-state conditions. The role of Tregs that are specific for pathogens, dietary antigens and allergens is much less studied, although recent data suggest a significant and previously underappreciated role for Tregs during memory responses to a wide range of foreign antigens. The development of TCR- or chimeric antigen receptor (CAR) transduced T cells means we are now able to engineer Tregs with disease-relevant antigen specificities, paving the way for ensuring specificity with Treg-based therapies. Understanding the role that antigens play in driving the generation and function of Tregs is critical for defining the pathophysiology of many immune mediated diseases, and developing new therapeutic interventions. PMID- 27256589 TI - Adenylate cyclase 3: a new target for anti-obesity drug development. AB - Obesity has become epidemic worldwide, and abdominal obesity has a negative impact on health. Current treatment options on obesity, however, still remain limited. It is then of importance to find a new target for anti-obesity drug development based upon recent molecular studies in obesity. Adenylate cyclase 3 (ADCY3) is the third member of adenylyl cyclase family and catalyses the synthesis of cAMP from ATP. Genetic studies with candidate gene and genome-wide association study approaches have demonstrated that ADCY3 genetic polymorphisms are associated with obesity in European and Chinese populations. Epigenetic studies have indicated that increased DNA methylation levels in the ADCY3 gene are involved in the pathogenesis of obesity. Furthermore, biological analyses with animal models have implicated that ADCY3 dysfunction resulted in increased body weight and fat mass, while reduction of body weight is partially explained by ADCY3 activation. In this review, we describe genomic and biological features of ADCY3, summarize genetic and epigenetic association studies of the ADCY3 gene with obesity and discuss dysfunction and activation of ADCY3. Based upon all data, we suggest that ADCY3 is a new target for anti-obesity drug development. Further investigation on the effectiveness of ADCY3 activator and its delivery approach to treat abdominal obesity has been taken into our consideration. PMID- 27256588 TI - An isoform of Nedd4-2 is critically involved in the renal adaptation to high salt intake in mice. AB - Epithelial sodium channels (ENaCs) play critical roles in the maintenance of fluid and electrolyte homeostasis, and their genetic abnormalities cause one type of hereditary salt-sensitive hypertension, Liddle syndrome. As we reported previously, both human and rodent Nedd4L/Nedd4-2 showed molecular diversity, with and without a C2 domain in their N-terminal. Nedd4L/Nedd4-2 isoforms with a C2 domain are hypothesized to be related closely to ubiquitination of ENaCs. We generated Nedd4-2 C2 domain knockout mice. We demonstrate here that loss of Nedd4 2 C2 isoform causes salt-sensitive hypertension under conditions of a high dietary salt intake in vivo. The knockout mice had reduced urinary sodium excretion, osmotic pressure and increased water intake and urine volume with marked dilatation of cortical tubules while receiving a high salt diet. To the contrary, there was no difference in metabolic data between wild-type and knockout mice receiving a normal control diet. In the absence of Nedd4-2 C2 domain, a high salt intake accelerated ENaC expression. Coimmunoprecipitation studies revealed suppressed ubiquitination for ENaC with a high salt intake. Taken together, our findings demonstrate that during a high oral salt intake the Nedd4-2 C2 protein plays a pivotal role in maintaining adaptive salt handling in the kidney. PMID- 27256590 TI - Non-random distribution of homo-repeats: links with biological functions and human diseases. AB - The biological function of multiple repetitions of single amino acids, or homo repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is significantly larger than expected from theoretical estimates. Analysis of statistical significance indicates that the minimal size of homo-repeats varies with amino acid type and proteome. In an attempt to characterize proteins harbouring long homo-repeats, we found that those containing polar or small amino acids S, P, H, E, D, K, Q and N are enriched in structural disorder as well as protein- and RNA-interactions. We observed that E, S, Q, G, L, P, D, A and H homo repeats are strongly linked with occurrence in human diseases. Moreover, S, E, P, A, Q, D and T homo-repeats are significantly enriched in neuronal proteins associated with autism and other disorders. We release a webserver for further exploration of homo-repeats occurrence in human pathology at http://bioinfo.protres.ru/hradis/. PMID- 27256591 TI - Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on upper and lower limb spasticity in post-stroke patients. AB - OBJECTIVES: The purpose of this study was to examine the effects of combined botulinum toxin type A (BoNT-A) and inpatient multidisciplinary (MD) rehabilitation therapy on the improvement of upper and lower limb function in post-stroke patients. METHODS: In this retrospective study, a 12-day inpatient treatment protocol was implemented on 51 post-stroke patients with spasticity. Assessments were performed on the day of admission, at discharge, and at 3 months following discharge. RESULTS: At the time of discharge, all of the evaluated items showed a statistically significant improvement. Only the Functional Reach Test (FRT) showed a statistically significant improvement at 3 months. In subgroup analyses, the slowest walking speed group showed a significantly greater change ratio of the 10 Meter Walk Test relative to the other groups, from the time of admission to discharge. This group showed a greater FRT change ratio than the other groups from the time of admission to the 3-month follow-up. CONCLUSION: Inpatient combined therapy of simultaneous injections of BoNT-A to the upper and lower limbs and MD may improve motor function. PMID- 27256592 TI - Spatial and non-spatial aspects of visual attention: Interactive cognitive mechanisms and neural underpinnings. AB - In humans and non-human primates, the parietal lobe plays a key role in spatial attention - the ability to extract information from regions of space. This role is thought to be mediated by "priority" maps that highlight attention-worthy locations, and provide top-down feedback for motor orienting and attentional allocation. Traditionally, priority signals within the parietal cortex have been characterized as being purely spatial, i.e., encoding the desired locus of gaze or attention regardless of the context in which the brain generates that selection. Here, we highlight evidence from human behavior and neuroimaging as well as monkey physiology, to argue that non-spatial responses are critical to the establishment of priority maps in parietal cortex. This review offers an integrative view of the role that parietal cortex plays in attentional selection, providing evidence that priority maps reflect spatial and non-spatial priorities that ultimately act on sensory information in a spatial way. PMID- 27256593 TI - Practice patterns in the management of acute intervertebral disc herniation in dogs. AB - OBJECTIVES: Acute intervertebral disc herniation is commonly managed by veterinary neurologists and surgeons. Anecdote suggests that patterns of management vary considerably and there is controversy surrounding many aspects of treatment. The goal of this study was to document patterns in management of acute spinal cord injury caused by acute intervertebral disc herniation among these two groups to aid in future discussions on best practices. METHODS: A survey querying diagnostic, medical and surgical practices for dogs with acute intervertebral disc herniation was distributed to diplomates on the databases of the American College of Veterinary Surgeons and the American College of Veterinary Internal Medicine (Neurology). RESULTS: Responses were received from 314 board-certified veterinary surgeons and neurologists. Both groups handled timing of decompression, surgical approach, and most postoperative recommendations in a similar fashion. Case volume differed between groups, with 77% of neurologists and 18% of surgeons managing e50 cases of acute intervertebral disc herniation per year. MRI was used most frequently as a diagnostic tool by neurologists (75%), while CT was used most commonly by surgeons (58%). Corticosteroids were routinely administered as a neuroprotective strategy by 34% of surgeons and 11% of neurologists. Disc fenestration was performed "always" or "most of the time" by 69% of neurologists and 36% of surgeons. CLINICAL IMPORTANCE: Understanding the common practices in the management of canine acute intervertebral disc herniation can provide a springboard for future discussions regarding the best practices in diagnosing and treating this disease. PMID- 27256594 TI - Helium-based cold atmospheric plasma-induced reactive oxygen species-mediated apoptotic pathway attenuated by platinum nanoparticles. AB - Plasma is generated by ionizing gas molecules. Helium (He)-based cold atmospheric plasma (CAP) was generated using a high-voltage power supply with low-frequency excitation (60 Hz at 7 kV) and He flow at 2 l/min. Platinum nanoparticles (Pt NPs) are potent antioxidants due to their unique ability to scavenge superoxides and peroxides. These features make them useful for the protection against oxidative stress-associated pathologies. Here, the effects of Pt-NPs on He-CAP induced apoptosis and the underlying mechanism were examined in human lymphoma U937 cells. Apoptosis was measured after cells were exposed to He-CAP in the presence or absence of Pt-NPs. The effects of combined treatment were determined by observing the changes in intracellular reactive oxygen species (ROS) and both mitochondrial and Fas dependent pathway. The results indicate that Pt-NPs substantially scavenge He-CAP-induced superoxides and peroxides and inhibit all the pathways involved in apoptosis execution. This might be because of the SOD/catalase mimetic effects of Pt-NPs. These results showed that the Pt-NPs can induce He-CAP desensitization in human lymphoma U937 cells. PMID- 27256595 TI - GCK gene mutations are a common cause of childhood-onset MODY (maturity-onset diabetes of the young) in Turkey. AB - OBJECTIVE: Inactivating heterozygous mutations in the GCK gene are a common cause of MODY and result in mild fasting hyperglycaemia, which does not require treatment. We aimed to identify the frequency, clinical and molecular features of GCK mutations in a Turkish paediatric cohort. DESIGN AND PATIENTS: Fifty-four unrelated probands were selected based on the following criteria: age of diagnosis <=17 years, family history of diabetes in at least two generations, anti-GAD/ICA negative, BMI<95.p and follow-up with diet, oral antidiabetic drug or low-dose insulin treatment (<=0.5U/kg/d). A MODY probability score (www.diabetesgenes.org) was calculated and 21 patients with a score >=75%, HbA1c levels <=7.5% (58.5 mmol/mol) and fasting blood glucose (FBG) levels 99-145 mg/dl (5.5-8.0 mmol/l) were selected for Sanger sequencing of the GCK gene. Targeted next-generation sequencing for all known monogenic diabetes genes was undertaken for any patient without a GCK gene mutation. RESULTS: GCK gene mutations (pathogenic or likely pathogenic variants) and a novel intronic variant of uncertain significance (c.208 + 3A>T) were identified in 13/54 probands (24%). Twelve of these patients had a MODY probability score >=75%. FBG level and 2-h glucose level in OGTT were 123 +/- 14 mg/dl (6.8 +/- 0.7 mmol/l) (107-157 mg/dl) and 181 +/- 30 mg/dl (10.1 +/- 1.6 mmol/l) (136-247 mg/dl), respectively. Average of glucose increment in OGTT was 58 +/- 27 mg/dl (3.2 +/- 1.5 mmol/l) (19-120 mg/dl), and mean HbA1c level was 6.5 +/- 0.5% (47.5 +/- 5.5 mmol/mol) (5.9-7.6%). Five novel missense mutations were identified (p.F123S, p.L58P, p.G246A, p.F419C, and p.S151C). Two patients treated with low-dose insulin before the molecular analysis were able to stop treatment. CONCLUSIONS: Approximately 1 in 4 MODY cases in this Turkish paediatric cohort have a GCK mutation. Selection of patients for GCK gene analysis using the MODY probability score was an effective way of identifying most (11/12) patients with a GCK mutation. PMID- 27256596 TI - Rebalancing gene haploinsufficiency in vivo by targeting chromatin. AB - Congenital heart disease (CHD) affects eight out of 1,000 live births and is a major social and health-care burden. A common genetic cause of CHD is the 22q11.2 deletion, which is the basis of the homonymous deletion syndrome (22q11.2DS), also known as DiGeorge syndrome. Most of its clinical spectrum is caused by haploinsufficiency of Tbx1, a gene encoding a T-box transcription factor. Here we show that Tbx1 positively regulates monomethylation of histone 3 lysine 4 (H3K4me1) through interaction with and recruitment of histone methyltransferases. Treatment of cells with tranylcypromine (TCP), an inhibitor of histone demethylases, rebalances the loss of H3K4me1 and rescues the expression of approximately one-third of the genes dysregulated by Tbx1 suppression. In Tbx1 mouse mutants, TCP treatment ameliorates substantially the cardiovascular phenotype. These data suggest that epigenetic drugs may represent a potential therapeutic strategy for rescue of gene haploinsufficiency phenotypes, including structural defects. PMID- 27256598 TI - [Common errors in empirical antibiotic treatment of severe sepsis]. PMID- 27256597 TI - The impact of audiovisual biofeedback on 4D functional and anatomic imaging: Results of a lung cancer pilot study. AB - BACKGROUND AND PURPOSE: The impact of audiovisual (AV) biofeedback on four dimensional (4D) positron emission tomography (PET) and 4D computed tomography (CT) image quality was investigated in a prospective clinical trial (NCT01172041). MATERIAL AND METHODS: 4D-PET and 4D-CT images of ten lung cancer patients were acquired with AV biofeedback (AV) and free breathing (FB). The 4D PET images were analyzed for motion artifacts by comparing 4D to 3D PET for gross tumor volumes (GTVPET) and maximum standardized uptake values (SUVmax). The 4D-CT images were analyzed for artifacts by comparing normalized cross correlation based scores (NCCS) and quantifying a visual assessment score (VAS). A Wilcoxon signed-ranks test was used for statistical testing. RESULTS: The impact of AV biofeedback varied widely. Overall, the 3D to 4D decrease of GTVPET was 1.2+/ 1.3cm(3) with AV and 0.6+/-1.8cm(3) for FB. The 4D-PET increase of SUVmax was 1.3+/-0.9 with AV and 1.3+/-0.8 for FB. The 4D-CT NCCS were 0.65+/-0.27 with AV and 0.60+/-0.32 for FB (p=0.08). The 4D-CT VAS was 0.0+/-2.7. CONCLUSION: This study demonstrated a high patient dependence on the use of AV biofeedback to reduce motion artifacts in 4D imaging. None of the hypotheses tested were statistically significant. Future development of AV biofeedback will focus on optimizing the human-computer interface and including patient training sessions for improved comprehension and compliance. PMID- 27256599 TI - [Definition and dignosis of sepsis 3.0]. PMID- 27256600 TI - [Antimicrobial algorithm for critical ill patients should be individualized based on guidelines]. PMID- 27256601 TI - [Individuation and precise antibiotic treatment guided by pharmacokinetics/pharmacodynamics in critically ill patients]. PMID- 27256602 TI - [Choice of antimicrobial agents in serious infections: broad-spectrum and individualization]. PMID- 27256603 TI - [The echocardiographic evaluation and its predicted prognosis of acute left cardiac systolic dysfunction in critically ill patients]. AB - OBJECTIVE: The purpose of this study was to evaluate the significance of echocardiography for the prognosis of acute left cardiac dysfunction in critically ill patients. METHODS: A prospective cohort study was conducted in patients with acute left cardiac dysfunction in the Department of Critical Care Medicine, Peking Union Medical College Hospital from June 2013 to June 2014. Patients were divided into four groups according to the echocardiographic manifestation, including biventricular failure, left ventricular failure, coronary related segmental movement disorder, non-coronary related segmental movement disorder. All patients were treated with standard hemodynamic therapy. The duration of cardiotonic drug use, the period of mechanical ventilation, the length of ICU stay and 28-day mortality rate were recorded. RESULTS: A total of 132 patients were retrospectively enrolled in this study. The incidence of coronary heart disease in the coronary related segmental movement disorder group (88.0%, 22/25) was higher than that in the other three groups (P<0.001), while other general clinical information between groups at baseline was comparable (P>0.05). Sepsis or septic shock was the main cause of acute left cardiac systolic dysfunction. The 28-day mortality rate in biventricular failure group was 21.05%, 19.05% in left ventricular failure group, 20.00% in coronary related segmental movement disorder group, and 1/10 in non-coronary related segmental movement disorder group (P<0.001). However, the duration of cardiotonic drug use, the period of mechanical ventilation, and the length of ICU stay were similar in all groups (P>0.05) .In biventricular failure group, previous history of left ventricular diastolic dysfunction significantly worsened the 28-day mortality rate (5/7, P<0.001). while diastolic dysfunction did not affect cardiotonic drug use, the period of mechanical ventilation and length of ICU stay(P>0.05). CONCLUSIONS: The different echocardiographic features of acute left cardiac systolic dysfunction in critically ill patients predict the different prognosis. We need to setup an evaluation system including left cardiac systolic/diastolic function and right cardiac function, which may improve the process of workflow. PMID- 27256604 TI - [The influence of left ventricular-arterial coupling on the prognosis of elderly patients with septic shock]. AB - OBJECTIVE: To investigate the influence of left ventricular-arterial coupling(VAC) on clinical prognosis of elderly patients with septic shock. METHODS: A total of 56 elderly septic shock patients were enrolled in this study, all of whom were admitted to Department of Intensive Care Unit in Zhejiang Hospital from August 2014 to October 2015.The patients were divided into two groups according to the status of left ventricular-arterial coupling when septic shock was diagnosed, which were left ventricular-arterial uncoupling group(UC group) and left ventricular-arterial coupling group(C group). Various parameters were recorded, including blood lactate level, central venous oxygen saturation(ScvO2), serum level of N-terminal pro-brain natriuretic peptide(NT proBNP) and cardiac troponin I(cTNI), dose of vasoactive drugs, the total fluid volume and urine volume per hour within 24 hours. The 28-day survival rate was a key index of prognosis. Multivariate logistic regression was taken to analyze risk factors related to death within 28 day. RESULTS: Compared with C group, UC group had lower values of left ventricular ejection fraction[(42.43+/-4.76)% vs (53.17+/-3.01)%; P<0.01] and cardiac index[(2.36+/-0.68) L.min(-1).m(-2) vs (2.93+/-0.45)L.min(-1).m(-2); P<0.01]. Yet serum levels of NT-proBNP[lg NT-proBNP 3.93+/-0.53 vs 3.40+/-0.63; P=0.004] and cTNI [lg cTNI-0.16+/-0.68 vs-1.03+/ 0.69; P<0.001] in UC group were higher than those in C group. Moreover, the total fluid volume within 24 hours [(3 806.3+/-831.4) ml vs (3 142.0+/-770.0) ml; P=0.016], blood lactate level[(5.61+/-2.68) mmol/L vs (3.93+/-1.59) mmol/L; P=0.043] and dose of norepinephrine[(0.630+/-0.300)MUg.kg(-1).min(-1) vs (0.292+/ 0.234)MUg.kg(-1).min(-1;) P=0.001] in UC group were greater than those in C group, while ScvO2[(60.75+/-2.91)% vs (64.42+/-2.19)%; P<0.001] and urine volume per hour[(0.518+/-0.358)ml vs (0.926+/-0.678)ml; P=0.007] were less than those in C group. Compared with C group, UC group had a lower 28-day survival rate[43.2%(19/44) vs 9/12; P=0.049]. Ea/Ees ratio was negatively correlated with LVEF, ScvO2(r=-0.686, P<0.001; r=-0.411, P=0.002), positively correlated with NT proBNP, cTNI(r=0.294, P=0.028; r=0.363, P=0.006), yet no obvious correlation was noticed with blood lactate level(r=0.170, P=0.21). Multiple logistic regression analysis showed that VAC(OR=11.187, 95%CI 2.489-50.285; P=0.002), lactate level (OR=1.727, 95%CI 1.164-2.563; P=0.007) and lg cTNI(OR=0.247, 95%CI 0.079-0.779; P=0.017) were independent risk factors affecting 28-day mortality. Conclutions: In elderly patients with septic shock, left ventricular-arterial uncoupling indicates a lower 28-day survival rate, worse cardiac function and tissue perfusion. Ea/Ees ratio might sever as a predictive indicator of 28-day mortality. PMID- 27256605 TI - [The changes of main upper gastrointestinal diseases and Helicobacter pylori infection status in the past thirty five years]. AB - OBJECTIVE: To study the spectrum of upper gastrointestinal diseases and infection rate of Helicobacter pylori(Hp)in our hospital during the past 35 years. METHODS: Patients who were 16 or older with duodenal ulcer, gastric ulcer, reflux esophagitis, gastric cancer and esophageal cancer diagnosed by gastroscopy and pathology were retrospectively enrolled in our study from January 1980 to December 2014.Patients with chronic superficial gastritis, chronic atrophic gastritis or Hp infection from January 1989 to December 2014 were also included in our study according to the same diagnostic criteria.The incidences of diseases and the infection rates of Hp were studied. RESULTS: A total of 213 495 patients underwent gastroscopy in our department during the past 35 years.The overall diagnostic rates of duodenal ulcer, gastric ulcer, reflux esophagitis, gastric cancer and esophageal cancer were 9.87%, 3.79%, 6.66%, 1.59% and 0.66% respectively.There were 183 426 patients receiving gastroscopy in our department from January 1989 to December 2014. The overall endoscopic diagnosis rates of chronic superficial gastritis and chronic atrophic gastritis were 49.83% and 22.43% respectively.The overall infection rate of Hp was 36.18%, which had a declining trend consistent with peptic ulcer (all P=0.000). Yet, the prevalence of reflux esophagitis, chronic superficial gastritis and chronic atrophic gastritis were increasing (all P=0.000). The diagnostic rates of gastric cancer and esophageal cancer were persistent (P=0.266, P=0.156). CONCLUSIONS: The Hp infection during years has been decreasing, consistent with the declining tendency of peptic ulcer.On the other hand, reflux esophagitis, chronic superficial gastritis and chronic atrophic gastritis show an ascendant trend.The proportion of patients with gastric cancer and esophageal cancer is relatively stable. PMID- 27256606 TI - [The incidence, clinical characteristics and risk factors of upper gastrointestinal bleeding in patients taking dual antiplatelet therapy after percutaneous coronary intervention in south China]. AB - OBJECTIVE: To investigate the incidence, clinical characteristics and risk factors of upper gastrointestinal bleeding (UGIB) in patients with acute coronary syndrome (ACS) who were administrated with aspirin and clopidogrel dual antiplatelet therapy after percutaneous coronary intervention (PCI). METHODS: ACS patients who had undergone PCI in the cardiovascular institute of Guangdong General Hospital from September 2009 to August 2014 were retrospectively enrolled.The incidence of UGIB and clinical characteristics of ACS patients on dual antiplatelet therapy for 1 year after PCI were analyzed.Risk factors of UGIB were screened in the cohort of patients and sex and age matched controls with ratio 1?3. RESULTS: A total of 9 118 ACS patients had undergone PCI and UGIB occurred in 189 patients (2.07%, 189/9 118) from September 2009 to August 2014. UGIB patients with history over one year, gastrointestinal tumors or varices or negative endoscopy were excluded.Thus the revised incidence of UGIB occurred was 0.61% in 56 patients (0.61%, 56/9 118) and appeared to decline year by year.Most patients (91.07%, 51/56) had melena or stool occult blood positive (OB+ ), while others had bloody stool or haematemesis.Most UGIB were ulcer-related which was proved by endoscopy, accounting for 67.86% (38/56). There were 24 cases with duodenal ulcer, 13 with gastric ulcer and 1 with complex ulcer, while others were gastric erosion, gastritis and duodenitis.The risk factors of UGIB were previous history of peptic ulcer (P<0.01) and renal impairment (P<0.01). On the other side, PPI intake was a protective factor (P<0.05). The incidence of new-onset ACS was 1.44% (50/3 464) in PPI group, compared with 1.34% (76/5 654) in no PPI group (P>0.05). PPI use for the prevention of UGIB after PCI didn't increase the recurrence of ACS. CONCLUSIONS: The incidence of UGIB is 0.61% in ACS patients on dual antiplatelet therapy (aspirin and clopidogrel) for 1 year after PCI and falls year by year.Administration of PPI after PCI protects patients from UGIB, especially in those with precious history of peptic ulcer and renal impairment. PMID- 27256607 TI - [An evaluation of plasma aldosterone-to-active-renin ratio in different postures in combination with aldosterone concentration in the diagnosis of aldosteronoma]. AB - OBJECTIVE: To investigate the diagnostic value of plasma aldosterone-to-active renin ratio(ARR)in combination with plasma aldosterone concentration(PAC)in the predication of aldosteronoma(APA). METHODS: A total of 85 APA and 155 essential hypertension(EH)patients from January 2012 to December 2014 in Chinese PLA General Hospital were enrolled. The ROC curve was applied to calculate the optimal cut-off points of ARR for APA. RESULTS: (1)The optimal cut-off point of supine ARR was 1 707.4(pmol/L)/(MUg.L(-1).h(-1))[61.64(ng/dl)/(MUg.L(-1).h(-1))] with the sensitivity, specificity and accuracy of 89.41%, 80.65% and 83.75%, respectively. The specificity and accuracy of the diagnostic value for APA increased (89.03% and 87.5% respectively) when supine ARR cut-off point were used in combination with supine PAC over 329.4 pmol/L. (2) The optimal cut-off point of upright ARR was 741.5 (pmol/L)/(MUg.L(-1).h(-1))[26.77(ng/dl)/(MUg.L(-1).h(-1) )]with the sensitivity, specificity and accuracy of 85.88%, 91.61% and 89.58%, respectively. Similarly, the specificity and accuracy greatly improved (94.84% and 91.67%, respectively) when upright ARR were applied together with upright PAC over 323.1 pmol/L. CONCLUSIONS: Both spine and upright ARR can be used in screening for APA. Moreover, the specificity and accuracy could be improved when ARR and PAC were used together both in the supine and upright position. PMID- 27256608 TI - [An analysis of immunophenotyping of peripheral lymphocytes in adult patients with infectious mononucleosis and chronic active Epstein-Barr virus infection]. AB - OBJECTIVE: To determine the immunophenotypic features of peripheral lymphocytes in adult patients with Epstein-Barr virus(EBV)-associated infectious mononucleosis(IM) and chronic active EBV infection (CAEBV). METHODS: Eighteen IM patients, 12 CAEBV patients and 18 healthy donors were included. Lymphocyte subsets including CD3(-)CD19(+) B cells, CD3(-)CD16/56(+) NK cells, CD4(+) and CD8(+) T cells in peripheral blood were measured by flow cytometry. The expression of activation markers (HLA-DR and CD38) on CD8(+) T cells and CD28 expression on T cells were also determined. Kruskal-Wallis H and Mann-Whitney U tests were used to compare variables among groups. RESULTS: IM patients had dramatically increased CD8(+) T cell counts than healthy donors (5.22*10(9)/L vs 0.54*10(9)/L, P<0.001). B cell counts moderately reduced in patients with IM than in healthy donors. No difference was found in absolute CD4(+) T cell and NK cell counts between IM and healthy donors. The levels of HLA-DR and CD38 on CD8(+) T cells significantly increased in IM patients compared with those in healthy controls. The intensity of CD28 on CD8(+) T cells significantly decreased, which was not seen on CD4(+) T cells. The median cell counts of B, NK, CD4(+) T and CD8(+) T subsets in CAEBV patients were 0.02*10(9)/L, 0.06*10(9)/L, 0.26*10(9)/L and 0.21*10(9)/L respectively, which were significantly lower than those in healthy donors (0.22*10(9)/L, 0.38*10(9)/L, 0.78*10(9)/L, 0.54*10(9)/L)and IM patients (0.12*10(9)/L, 0.40*10(9)/L, 0.91*10(9)/L, 5.22*10(9)/L). The positive rates of HLA-DR and CD38 on CD8(+) T cells in CAEBV patients were higher than those in healthy controls, but lower than those in IM patients. CONCLUSIONS: The immunophenotypic pattern in adult patients with IM is characterized by a dramatic increase of extensively activated CD8(+) T cells, a moderate reduction of CD19(+) B cells and no significant change of CD4(+) T cells and CD16/56(+) NK cells. CAEBV is featured by an immunosuppression status as demonstrated by significantly decreased B, NK, CD4(+) T and CD8(+) T subsets. PMID- 27256609 TI - [The correlation factor analysis for conversion of clinically isolated syndrome to multiple sclerosis and neuromyelitis optica]. AB - OBJECTIVE: To analyze the features of patients who converted from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and neuromyelitis optica (NMO) and explore the correlated factors. METHODS: A total of 151 patients admitted in our unit as CIS from January 2009 to December 2014 were enrolled in the study. All patients were divided into the following four groups by locations of the initial lesion, which were the spinal cord, the optic nerve, the brain stem and the multifocal lesions. Data were collected at the baseline including demographics, expanded disability status scale (EDSS) score, site of CIS, presence or absence of cerebrospinal fluid (CSF) oligoclonal bands (OB) and serum aquaporin-4 antibody (AQP4-Ab), evoked potential (EP) and MRI lesions. The conversion rates from CIS to clinically definite MS or NMO were calculated and the correlated factors were explored. RESULTS: With a mean follow-up period of (44.11+/-17.62)months, 46/151(30.5%) patients converted to MS, 28/151 (18.5%) to definite NMO and 66/151 patients(43.7%)remained as CIS. Other patients were converted to optic neuritis(4/151), one-time transverse myelitis(3/151), acute disseminated encephalomyelitis (1/151) and Balo concentric sclerosis(3/151) . The EDSS score was significantly higher in patients converted to NMO than those converted to MS (P=0.003). The initial manifestation of optic neuritis significantly correlated with the conversion to NMO (P=0.000), while the initial manifestation of CIS with multifocal lesions significantly correlated with the conversion to MS (P=0.000). Neither the isolated BAEP (P=0.703), VEP (P=0.076), SEP (P=0.915) nor the combination of two (P=0.546)or three (P=1.000) of the above parameters could help to distinguish the conversion to MS or NMO. More patients with positive CSF-OB converted to MS (P=0.001), while more patients with positive serum AQP4-Ab converted to NMO (P=0.001). More patients were serum AQP4-Ab positive in those converted to NMO than those converted to MS (P=0.000). Lesions longer than three vertebral segments were dominant in patients converted to NMO (P=0.000). The logistic regression analysis revealed that factors correlated with conversion from CIS to MS were the initial CIS manifestation of multifocal lesions (OR=4.775, P=0.002), positive CSF-OB (OR=7.794, P=0.002) and VEP abnormality (OR=7.251, P=0.001). Factors correlated with conversion from CIS to NMO were female in gender (OR=12.536, P=0.019), positive serum AQP4-Ab (OR=36.410, P=0.002), lesions longer than three vertebral segments (OR=93.602, P=0.001), abnormal VEP and SEP (OR=18.448, P=0.002; OR=12.731, P=0.016). CONCLUSIONS: Factors correlated with the conversion from CIS to MS are initial CIS manifestation of multifocal lesions, positive CSF-OB and abnormal VEP, while those correlated with the conversion from CIS to NMO are female in gender, positive serum AQP4-Ab, initial CIS manifestation with optic nerve, lesions involved more than three vertebral segments and abnormal VEP and SEP. PMID- 27256610 TI - [A comparison of clinical characteristics in elderly patients with ulcerative colitis and ischemic colitis]. AB - OBJECTIVE: To analyze the discrepancy and similarities of clinical characteristics in elderly patients with ulcerative colitis (UC) and ischemic colitis (IC). METHODS: A total of 43 elderly patients (age>=60 yrs) with UC and 36 elderly patients with IC were enrolled from 2004 to 2015 at Peking Union Medical College Hospital. The clinical characteristics were retrospectively analyzed and compared between the two groups. RESULTS: Compared with IC group, the disease course was longer with lower incidence of cardiovascular comorbidities in UC patients (P<0.05). In UC group, more patients presented with diarrhea, mucopurulent bloody stool [39(90.7%) vs 16(44.4%) and 34(79.1%) vs 2(5.6%) respectively, both P<0.01]. Yet bloody stool as the only symptom was seen in more IC patients than UC patients [61.1%(22/36) vs 7.0%(3/43), P<0.01]. The ratio of extra-intestinal manifestations was higher [18.6%(8/43) vs 0(0/36)] in UC patients, while complications were lower [11.6%(5/43) vs 30.6%(11/36), P<0.05]. As to the laboratory parameters, median platelet count [(294.38+/ 104.83)*10(9)/L vs (235.47+/-94.82)*10(9)/L, P<0.05] was higher in UC group. In addition, more patients with UC had positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA) [50.0%(15/30) vs 10.0%(2/20), P<0.05]. The most commonly involved regions of IC were descending colon and sigmoid colon, in which the lesions were clearly demarcated with the normal mucosa. Lesions in patients with UC mainly originated from rectum and might spread to the whole colon. Vascular occlusion and micro thrombosis were characteristic pathological findings of IC. The crypt abscesses were frequently seen in the UC group. CONCLUSION: Even though UC and IC have some similar manifestations in the elderly patients, clinical and pathological discrepancy is still helpful to differentiate each other. PMID- 27256611 TI - [The role of color doppler ultrasonography, thyroid function and auto antibody for the screening of Graves' disease in pregnancy]. AB - OBJECTIVE: To determine whether color doppler ultrasonography (CDU), thyroid function or thyroid autoimmune antibodies could identify Graves' disease in pregnancy(GDP) in pregnant patients with newly diagnosed thyrotoxicosis. METHODS: It is an observational study. Sixty-eight pregnant patients with newly diagnosed thyrotoxicosis including gestational hyperthyroidism(GHT) subjects (GHT group, n=33) and GDP subjects (GDP group, n=35), and 62 age-and sex-matched healthy subjects (C1 group: pregnant, n=32, C2 group: non-pregnant, n=30) were recruited. Thyroid function, human chorionic gonadotropin(HCG), thyroid autoimmune antibodies were detected. Peak systolic velocity of the superior thyroid artery (STA-PSV) and diastole inner diameter(STA-D) of the superior thyroid artery were measured by CDU. A ROC curve was used to evaluate STA-PSV, STA-D, thyroid function and thyroid autoimmune antibodies for identification of GDP. RESULTS: The area under the ROC curve of STA-PSV, STA-D and thyroid stimulating hormone (TSH), free T4 (FT4) for GDP were 0.905, 0.887, 0.803 and 0.786, respectively. The optimal cut-off points of STA-PSV, STA-D, TSH and FT4 for GDP were 40 cm/s, 2.0mm, 0.03 mIU/L and 30 pmol/L with the sensitivity of 82.9%, 72.1%, 81.8%, 76.2% and specificity of 81.8%, 87.9%, 75.2%, 80.3%, respectively. CONCLUSIONS: Detection of STA-PSV and STA-D by CDU, as well as thyroid function, is useful in screening GDP in pregnant patients with thyrotoxicosis. PMID- 27256612 TI - Sleep duration and blood pressure: a longitudinal analysis from early to late adolescence. AB - The aim of this study was to evaluate the association between sleep duration and blood pressure using a cross-sectional and longitudinal approach. As part of a population-based cohort, 1403 adolescents were evaluated at 13 and 17 years old. Sleep duration was estimated by the difference between self-reported usual bedtime and wake-up time. Blood pressure was measured using the auscultatory method. Regression coefficients (beta) and respective 95% confidence intervals were computed to evaluate the association between sleep duration and blood pressure, using linear regression models adjusted for practice of sports and body mass index at 17 years old. The mean (standard deviation) sleep duration at 13 years old was 9.0 (0.76) h per day, and on average it decreased by 46 min up to 17 years old. The median (25th-75th) systolic blood pressure at 17 years old was 110.0 (103.5-119.0) mmHg in females and 114.0 (106.0-122.0)mmHg in males (P < 0.001); for diastolic blood pressure the values were 66.0 (60.0-71.0) and 69.0 (62.0-75.0) mmHg, respectively (P < 0.001). In cross-sectional analysis, at 17 years old, after adjustment, a positive association was found between sleep duration and blood pressure, significant only for systolic blood pressure among females [beta = 0.730 (0.005; 1.455)]. In girls, no significant association was found between sleep duration at 13 years old and blood pressure at 17 years old, but in males an inverse association was found between sleep duration at 13 years old and blood pressure at 17 years old significant only for systolic blood pressure [beta = -1.938 (-3.229; -0.647)]. This study found no association between sleep duration at 13 years old and blood pressure at 17 years old in girls, but among males an inverse association was found. PMID- 27256613 TI - Progression from First Drink, First Intoxication, and Regular Drinking to Alcohol Use Disorder: A Comparison of African American and European American Youth. AB - BACKGROUND: Differences between African Americans (AAs) and European Americans (EAs) in the prevalence and age at onset of alcohol use and alcohol use disorder (AUD) have been documented, but distinctions in the timing of early stage transitions and contribution of various psychiatric and psychosocial risk factors to the progression from initiation to AUD have yet to be investigated. The current study characterized progression from alcohol use initiation-defined alternatively as first drink, first intoxication, and regular drinking onset-to AUD in AA and EA youth. METHODS: Psychiatric interviews were administered via telephone to 1,461 participants (56% AA, 44% EA) in a high-risk family study (50.3% female, mean age = 17.6 [SD = 3.8]). Cox proportional hazards regression analyses were conducted separately for the AA and EA subsamples to predict DSM-5 AUD as a function of age at alcohol use initiation, with age at first drink, age at first intoxication, and age at regular drinking onset as the point of origin in separate models. RESULTS: Across race/ethnicity, regardless of how it was measured, early alcohol use initiation predicted AUD, but hazard ratios (HRs) were lowest for first drink. Regular smoking and social anxiety disorder were significant predictors in both racial/ethnic groups, but associations with conduct disorder (all 3 models: HR range = 2.07 to 4.15) and major depressive disorder (regular drinking: HR = 4.51, confidence interval [CI]: 1.60 to 12.69 for AUD onset >= age 20) were specific to AAs. Posttraumatic stress disorder (HR = 5.38, CI: 1.44 to 20.08) and generalized anxiety disorder (HR = 7.35, CI: 2.31 to 23.34 for AUD onset <= age 17) were strongly associated with progression from regular drinking to AUD exclusively in EAs. CONCLUSIONS: Early alcohol use initiation is a marker of risk for AUD in both AA and EA youth, but the contributions of various psychiatric risk factors to the development of AUD are not universal across racial/ethnic groups. PMID- 27256614 TI - The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome. AB - We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole-exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant. PMID- 27256615 TI - Surface-Enhanced Raman Scattering of Silicon Nanocrystals in a Silica Film. AB - Surface-enhanced Raman scattering (SERS) is an intriguing effect, efficiency of which depends on many factors and whose applicability to a given system is not obvious before the experiment. The motivation of the present work is to demonstrate the SERS effect on silicon nanocrystals (Si-nc) embedded in silica, the material of high technological importance. Using the Ag overlayer method, we have found the SERS effect for this material. The best result is obtained for Ag layers of a weight thickness of 12 nm, whose surface plasmons are in a resonance with the laser wavelength (488 nm). The enhancement obtained for the Raman signal from 3-4-nm Si-nc in a 40-nm SiOx film is above 100. The SERS effect is about twice stronger for ultra-small Si-nc (~1 nm) and/or disordered silicon compared to Si-nc with sizes of 3-4 nm. The SERS measurements with an Ag overlayer allow detecting silicon crystallization for ultra-thin SiOx films and/or for very low Si excess and suppress the Raman signal from the substrate and the photoluminescence of the film. PMID- 27256616 TI - PC-FACS. AB - PC-FACS(FastArticleCriticalSummaries for Clinicians inPalliativeCare) provides hospice and palliative care clinicians with concise summaries of the most important findings from more than 100 medical and scientific journals. If you have colleagues who would benefit from receiving PC-FACS, please encourage them to join the AAHPM at aahpm.org. Comments from readers are welcomed at pc facs@aahpm.org. PMID- 27256617 TI - "Mother MD Intense": The Need for Intentional Healing. PMID- 27256618 TI - Erratum to: Sublingual Fentanyl Tablets for Relief of Breakthrough Pain in Cancer Patients and Association with Quality-of-Life Outcomes. PMID- 27256619 TI - Vertically aligned zinc oxide nanowires electrodeposited within porous polycarbonate templates for vibrational energy harvesting. AB - A piezoelectric nanogenerator has been fabricated using a simple, fast and scalable template-assisted electrodeposition process, by which vertically aligned zinc oxide (ZnO) nanowires were directly grown within a nanoporous polycarbonate (PC) template. The nanowires, having average diameter 184 nm and length 12 MUm, are polycrystalline and have a preferred orientation of the [100] axis parallel to the long axis. The output power density of a nanogenerator fabricated from the as-grown ZnO nanowires still embedded within the PC template was found to be 151 +/- 25 mW m(-3) at an impedance-matched load, when subjected to a low-level periodic (5 Hz) impacting force akin to gentle finger tapping. An energy conversion efficiency of ~4.2% was evaluated for the electrodeposited ZnO nanowires, and the ZnO-PC composite nanogenerator was found to maintain good energy harvesting performance through 24 h of continuous fatigue testing. This is particularly significant given that ZnO-based nanostructures typically suffer from mechanical and/or environmental degradation that otherwise limits their applicability in vibrational energy harvesting. Our template-assisted synthesis of ZnO nanowires embedded within a protective polymer matrix through a single growth process is thus attractive for the fabrication of low-cost, robust and stable nanogenerators. PMID- 27256620 TI - Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens. AB - Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life. PMID- 27256621 TI - Populations of the Minor alpha-Conformation in AcGXGNH2 and the alpha-Helical Nucleation Propensities. AB - Intrinsic backbone conformational preferences of different amino acids are important for understanding the local structure of unfolded protein chains. Recent evidence suggests alpha-structure is relatively minor among three major backbone conformations for unfolded proteins. The alpha-helices are the dominant structures in many proteins. For these proteins, how could the alpha-structures occur from the least in unfolded to the most in folded states? Populations of the minor alpha-conformation in model peptides provide vital information. Reliable determination of populations of the alpha-conformers in these peptides that exist in multiple equilibriums of different conformations remains a challenge. Combined analyses on data from AcGXPNH2 and AcGXGNH2 peptides allow us to derive the populations of PII, beta and alpha in AcGXGNH2. Our results show that on average residue X in AcGXGNH2 adopt PII, beta, and alpha 44.7%, 44.5% and 10.8% of time, respectively. The contents of alpha-conformations for different amino acids define an alpha-helix nucleation propensity scale. With derived PII, beta and alpha-contents, we can construct a free energy-conformation diagram on each AcGXGNH2 in aqueous solution for the three major backbone conformations. Our results would have broad implications on early-stage events of protein folding. PMID- 27256622 TI - Resolvin D2 decreases TLR4 expression to mediate resolution in human monocytes. AB - TLRs are critical for innate immunity, but excessive activation can lead to tissue damage and disease. Specialized proresolving mediators (SPMs), including resolvin D2 (RvD2), promote the active resolution of inflammation. How SPMs regulate early LPS signaling, including activation of TLR4, is unknown. We treated human THP-1 monocytic cells and primary human blood monocytes with RvD2 and LPS to evaluate modulation of TLRs. miRNA-146a overexpression and inhibition were used to dissect the mechanism of RvD2-mediated actions. We validated our studies using ELISAs for cytokines, PCR, Western blot analysis, and flow cytometry. Cells treated with 0.1% ethanol (control for RvD2) and/or PBS (control for LPS), and control microRNA mimics and inhibitors were used as controls. RvD2 reduced LPS-induced cytokines and TLR4 expression in human monocytes by up to 75%. In THP-1 cells, RvD2 reduced expression of TLR4, lymphocyte antigen 96 (MD 2), and downstream signals (MyD88, TRIF, and TAK1). These effects were partially mediated through RvD2 induction of microRNA-146a, and RvD2's actions were blocked by microRNA-146a inhibition. These new findings reveal the ability of RvD2 to reduce TLR4 expression and attenuate LPS-induced inflammation, providing a new area of SPM activity to investigate in this major area of therapeutic research. Croasdell, A., Sime, P. J., Phipps, R. P. Resolvin D2 decreases TLR4 expression to mediate resolution in human monocytes. PMID- 27256624 TI - Adults with cystic fibrosis in Portugal: A first step towards improvement. PMID- 27256623 TI - Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. AB - In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 +/- 6.3 kg/m(2); 46 +/- 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P < 0.00001). Insulin sensitivity reached its maximum (acrophase) around noon, being 54% higher than during midnight (P = 0.009). The amplitude of the rhythm was positively correlated with in vivo sleep duration (r = 0.53; P = 0.023) and negatively correlated with in vivo bedtime (r = -0.54; P = 0.020). No circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martinez Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. PMID- 27256625 TI - Parenting practices and styles associated with adolescent sexual health in Dar es Salaam, Tanzania. AB - Parenting styles and practices are suggested to be important predictors of adolescent sexual health, mostly in Europe and North America. Limited research has been conducted on these processes in Sub-Saharan Africa, which has different patterns of adolescent sexual behavior and family traditions. This study qualitatively explored parenting practices and styles associated with adolescent sexual health in Tanzania, with 12 adolescents and 12 parents of adolescents. The themes we identified from the data included parental monitoring, preventive, and punitive behaviors. Parents were reported to use mostly punitive behaviors to correct or prohibit sexual behavior; parents also set clear rules about appropriate sexual behavior (e.g., modesty and abstinence). Parents were also reported to closely monitor their adolescent children's friendships and sexual behavior to minimize sexual behavior. However, some parents also engaged in positive preventive practices aimed at protecting their adolescent children. PMID- 27256626 TI - Psychiatric Emergencies for Clinicians: The Emergency Department Management of Thyroid Storm. PMID- 27256627 TI - Comment on: "Timely Pain Management in the Emergency Department". PMID- 27256628 TI - Cellulose nanocrystal interactions probed by thin film swelling to predict dispersibility. AB - The production of well-dispersed reinforced polymer nanocomposites has been limited due to poor understanding of the interactions between components. Measuring the cohesive particle-particle interactions and the adhesive particle polymer interactions is challenging due to nanoscale dimensions and poor colloidal stability of nanoparticles in many solvents. We demonstrate a new cohesive interaction measurement method using cellulose nanocrystals (CNCs) as a model system; CNCs have recently gained attention in the composites community due to their mechanical strength and renewable nature. Multi-wavelength surface plasmon resonance spectroscopy (SPR) was used to monitor the swelling of CNC thin films to elucidate the primary forces between CNCs. This was achieved by measuring swelling in situ in water, acetone, methanol, acetonitrile, isopropanol, and ethanol and relating the degree of swelling to solvent properties. Films swelled the most in water where we estimate 1.2-1.6 nm spacings between CNCs (or 4-6 molecular layers of water). Furthermore, a correlation was found between film swelling and the solvent's Hildebrand solubility parameter (R(2) = 0.9068). The hydrogen bonding component of the solubility parameters was more closely linked to swelling than the polar or dispersive components. The films remained intact in all solvents, and using DLVO theory we have identified van der Waals forces as the main cohesive interaction between CNCs. The trends observed suggest that solvents (and polymers) alone are not sufficient to overcome CNC-CNC cohesion and that external energy is required to break CNC agglomerates. This work not only demonstrates that SPR can be used as a tool to measure cohesive particle-particle interactions but additionally advances our fundamental understanding of CNC interactions which is necessary for the design of cellulose nanocomposites. PMID- 27256629 TI - Dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett's esophagus risk: a systematic review and meta-analysis. AB - The relationships between dietary fruit, vegetable, fat, and red and processed meat intakes and Barrett's esophagus (BE) risk remain inconclusive. We conducted a systematic review and meta-analysis to summarize the available evidence on these issues. PubMed, EMBASE and the Cochrane Library were searched for studies published from inception through October 2015. A total of eight studies were included in this analysis. Fruit intake was not associated with BE risk (OR = 0.65, 95% CI = 0.37-1.13), but vegetable intake was strongly associated with BE risk (OR = 0.45, 95% CI = 0.29-0.71). Saturated fat, red meat and processed meat intakes were not associated with BE risk with OR = 1.25 (95% CI = 0.82-1.91), OR = 0.85 (95% CI = 0.61-1.17) and OR = 1.03 (95% CI = 0.73-1.46), respectively. Dietary vegetable not fruits intake may be associated with decreased BE risk. Fat and red and processed meat intakes may not contribute to an increased BE risk. Well-designed, large prospective studies with better established dose-response relationships are needed to further validate these issues. PMID- 27256630 TI - Casimir switch: steering optical transparency with vacuum forces. AB - The Casimir force, originating from vacuum zero-point energy, is one of the most intriguing purely quantum effects. It has attracted renewed interests in current field of nanomechanics, due to the rapid size decrease of on-chip devices. Here we study the optomechanically-induced transparency (OMIT) with a tunable Casimir force. We find that the optical output rate can be significantly altered by the vacuum force, even terminated and then restored, indicating a highly-controlled optical switch. Our result addresses the possibility of designing exotic optical nano-devices by harnessing the power of vacuum. PMID- 27256632 TI - Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases. AB - The invasion cascade exhibited by placental trophoblasts and cancerous cells bears many similarities, and it is attributed to extracellular matrix degradation mediated by matrix metalloproteinases (MMPs). Although proper and controlled invasion by trophoblasts into the maternal uterus is an essential requirement for maintenance of normal pregnancy, any abnormality in this phenomenon results in the development of invasion-related disorders such as gestational trophoblastic diseases (GTDs) and preeclampsia. We studied the epigenetic basis of differential expression of two placental MMPs (MMP2 and MMP9) and tissue inhibitors of metalloproteinases (TIMP2 and TIMP1) during normal gestation and invasion-related disorders, i.e., preeclampsia and GTDs. Our study suggests the association of H3K9/27me3 with differential expression of these MMPs and their inhibitors, which regulate the placental invasion during normal pregnancy, whereas no role of CpG methylation was observed in the differential expression of MMPs/TIMPs. Further, development of GTDs was associated with abnormally higher expression of these MMPs and lower levels of their inhibitors, whereas the reverse trends were observed for MMPs and their TIMPs in case of preeclampsia, in association with abnormal changes in H3K9/27me3. These results suggest the involvement of higher levels of MMPs in an aggressive invasive behavior depicted by GTDs, whereas lower levels of these MMPs in shallow and poor invasive phenotype associated with preeclampsia. Thus, our study shows the significance of a proper balance regulated by histone trimethylation between differential expression of MMPs and their TIMPs for maintaining normal pregnancy and its deregulation as a contributing factor for pathogenesis of invasive disorders during pregnancy. PMID- 27256631 TI - In vivo xenoestrogenic actions of cadmium and arsenic in anterior pituitary and uterus. AB - Cadmium (Cd) and arsenic (iAs) are toxic metals ubiquitously present in the environment. Both pollutants exert nonmonotonic dose responses, being mostly cytotoxic at high concentrations but mimicking estrogen (E2) effects at low doses. Xenoestrogenic activity of Cd and iAs has been demonstrated in different hormone-dependent tumor cell lines; however, their actions in vivo remain largely unknown. Here, we investigated whether in vivo administration of low doses of Cd and iAs through drinking water would display xenoestrogenic effects in the anterior pituitary gland and uterus of ovariectomized rats. Cd (1ppm) and iAs (0.1ppm) exposure increased the wet weight of anterior pituitary gland and uterus and induced proestrus- and estrus-like vaginal smears. Both metals stimulate cell proliferation of these tissues as they increased the expression of proliferation markers. More importantly, they augmented soluble guanylyl cyclase alpha1 subunit expression, which has been linked to hormone-dependent tumor progression. Also, Cd and iAs modified protein levels of full-length estrogen receptor alpha and its truncated variants in an E2-like manner. Anterior pituitary hormone secretion was differentially affected by both metals. Luteinizing hormone synthesis and release were strongly diminished after Cd exposure and only mildly reduced by iAs. Both metals were able to increase prolactin synthesis, although only iAs augmented serum prolactin levels. This study shows for the first time that Cd and iAs exert strong xenoestrogenic effects on anterior pituitary gland at low doses. The differences between Cd and iAs E2-like behavior indicate that other Cd- and iAs specific mechanisms could be involved. Altogether, these results contribute to the knowledge of reproductive disorders associated with Cd and iAs environmental contamination. PMID- 27256633 TI - Early detection of bilateral cataracts in utero may represent a manifestation of severe congenital disease. AB - We observed bilateral cataracts on second trimester ultrasound, in two consecutive pregnancies, with no other structural defects detected. The parents were unrelated and had no family history for the disease. The first pregnancy was terminated in week 22. Copy number variation analysis revealed, in both the aborted fetus and the mother, a 495 kb duplication at 22q11.23 encompassing CRYBB3 and CRYBB2, and not present in variation databases. In the second pregnancy, lens hyperechogenicity was detected by ultrasound at week 13 and 4 days. The identical duplication at 22q11.23 was found in the fetus and considered as possibly pathogenic. At weeks 22 and 30, smaller orbit measurements were elucidated on ultrasound, raising concerns as to the underlying molecular genetic cause, necessitating further investigation. Whole-exome sequencing, using DNA of the first fetus, was performed shortly after the birth of a male child, and two truncating RAB3GAP1 mutations were detected: c.538G>T; p. (Glu180*) and c.943C>T; p. (Arg315*). Neither mutation has been previously reported to be disease causing; however, evaluation in the context of previously published literature indicated their deleterious nature, implying a clinical diagnosis of Warburg micro syndrome or Martsolf syndrome. Sanger sequencing confirmed segregation of the two mutations within the family, consistent with autosomal recessive inheritance. The child born from the second pregnancy showed features typical of Warburg micro syndrome, with the exception of microcephaly, at age 31 months. (c) 2016 Wiley Periodicals, Inc. PMID- 27256634 TI - The Development of a Technology-Based Hierarchy to Assess Chronic Low Back Pain and Pain-Related Anxiety From a Fear-Avoidance Model. AB - Previous studies have not examined the assessment of chronic low back pain (CLBP) and pain-related anxiety from a fear avoidance model through the use of motion capture software and virtual human technologies. The aim of this study was to develop and assess the psychometric properties of an interactive, technologically based hierarchy that can be used to assess patients with pain and pain-related anxiety. We enrolled 30 licensed physical therapists and 30 participants with CLBP. Participants rated 21 video clips of a 3-D animated character (avatar) engaging in activities that are typically feared by patients with CLBP. The results of the study indicate that physical therapists found the virtual hierarchy clips acceptable and depicted realistic patient experiences. Most participants with CLBP reported at least 1 video clip as being sufficiently anxiety-provoking for use clinically. Therefore, this study suggests a hierarchy of fears can be created out of 21 virtual patient video clips paving the way for future clinical use in patients with CLBP. PERSPECTIVE: This report describes the development of a computer-based virtual patient system for the assessment of back pain-related fear and anxiety. Results show that people with back pain as well as physical therapists found the avatar to be realistic, and the depictions of behavior anxiety- and fear-provoking. PMID- 27256635 TI - Physical Activity and Anthropometric Characteristics Among Urban Youth in Mexico: A Cross-Sectional Study. AB - BACKGROUND: Obesity is a critical problem among Mexican youth, but few studies have investigated associations among physical activity (PA) modes and anthropometrics in this population. This study examined associations among active commuting to school (ACS), sports or other organized PA, outdoor play, and body mass index (BMI) percentile and waist circumference (WC) among Mexican youth. METHODS: Parents of school children (N = 1996, ages 6 to 14 years, 53.1% female) in 3 Mexican cities reported PA participation using the (modified) fourth grade School Physical Activity and Nutrition Survey. Trained assessors measured BMI percentile and WC in person. RESULTS: Parents reported that 52.3% of children engaged in ACS, 57.3% participated in sports or organized PA, and a median of 2 days in the previous week with at least 30 minutes of outdoor play. In complete case analyses (n = 857), ACS was negatively associated with BMI percentile, and outdoor play was negatively associated with WC after adjusting for school, age, sex, and income. In analyses incorporating data from multiple imputation (N = 1996), outdoor play was negatively associated with WC (all Ps < . 05). CONCLUSIONS: ACS and outdoor play are favorably associated with anthropometrics and may help prevent childhood obesity in Mexico. ACS and outdoor play should be priorities for increasing youth PA in Mexico. PMID- 27256636 TI - Parkinson disease: Dopamine receptor variants improve response to rasagiline in PD. PMID- 27256637 TI - Alzheimer disease: NSAIDs protect neurons and preserve memory in a mouse model of AD. PMID- 27256638 TI - Total synthesis of xiamenmycin C and all of its stereoisomers: stereochemical revision. AB - Xiamenmycin C, a potent anti-fibrotic natural product, and all of its stereoisomers have been synthesized and their structures were fully characterized. Based on this study, the originally proposed structure of xiamenmycin C has been accordingly revised to be 2R,3S. PMID- 27256639 TI - Comparative proteomic analysis of tear fluid in Graves' disease with and without orbitopathy. AB - BACKGROUND: Graves' orbitopathy (GO) is a severe organ-specific autoimmune inflammatory ocular complication most often associated with Graves' disease (GD). Besides the cosmetic problems these patients develop, GO may also cause severe, sight-threatening complications. Additionally, GO complicates the treatment of patients with GD, making the identification of Graves patients at risk for eye disease before they develop symptoms a critical step in the clinical management and quality of life of these patients. The high concentration of proteins in tear fluid makes it an important source for studying potential protein biomarkers for GO. PATIENTS AND METHODS: The aim of this study was to quantitatively compare tear fluid from GD patients with moderate/severe GO (GO) and patients with GD without GO (controls) using untargeted quantitative proteomics based on dimethyl labelling in combination with two-dimensional liquid chromatography-mass spectrometry. RESULTS: Among the 1212 proteins identified, 16 showed significant alterations in abundance between the two groups. Thus, in this study, we reveal a number of novel dysregulated proteins in GO which may contribute to a better understanding of the disease. In particular, upregulation of lacrimal gland proteins such as lysozyme C, lacritin, antileukoproteinase and zinc-alpha-2 glycoprotein 1 suggests involvement of the lacrimal gland in the pathogenesis of GO. CONCLUSIONS: It remains to be elucidated whether some of these proteins can be used as markers for patients at risk for developing GO as well as useful indicators for disease activity. PMID- 27256640 TI - Impact of 3'UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population. AB - OBJECTIVE: Several studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3' untranslated region (3'UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3'UTR regions of the KRAS gene and the effect of KRAS 3'UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT. METHODS: Codons 12, 13, and 61 and 3'UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients. RESULTS: We defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3'UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required. PMID- 27256642 TI - Strengthening primary health care to improve Indigenous health outcomes. PMID- 27256643 TI - Medicines and dementia consumer campaign. PMID- 27256641 TI - Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study. AB - BACKGROUND: Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30-60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC. METHODS: We conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed. RESULTS: Median overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (<=5 ng/ml) (6.8 vs. 10.3 months, respectively; p < 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45-2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71-1.40). CONCLUSIONS: The present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA. PMID- 27256645 TI - Potential risks and benefits of nanotechnology: perceptions of risk in sunscreens. PMID- 27256646 TI - Medicinal cannabis in Australia: the missing links. PMID- 27256647 TI - Governing the reform of the medical internship. PMID- 27256648 TI - Epidemiology, clinical impacts and current clinical management of Helicobacter pylori infection. AB - Helicobacter pylori infection is a major cause of morbidity and mortality worldwide. More than 50% of the global population is estimated to be infected. Differences in prevalence exist within and between countries, with higher prevalence seen among people with lower socio-economic status. Most transmission of infection occurs early in life, predominantly from person to person in the family setting. H. pylori is the cause of most peptic ulcer disease, gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and causes symptoms in a subset of patients with functional dyspepsia. Choice of diagnostic test depends on the clinical context; urea breath tests and endoscopy with biopsy are the major diagnostic tools. Evidence-based indications for eradication of H. pylori infection are well documented. The most widely used and recommended eradication therapy in Australia is triple therapy comprising a proton pump inhibitor, amoxycillin and clarithromycin, usually for 1 week. Effective alternative regimens are available for patients with proven allergy to penicillin. Antimicrobial resistance is the major determinant of the outcome of eradication therapy. Trends in antibiotic resistance need to be monitored locally, but individual patient susceptibility testing is not usually necessary as it rarely guides the choice of therapy. The outcome of treatment should be assessed not less than 4 weeks after therapy. This is usually done with a urea breath test if follow-up endoscopy is not required. When first-line therapy fails, several proven second-line therapies may be used. Repeat first-line therapy and ad hoc regimens should be avoided. Overall cumulative eradication rates should approach 99%. PMID- 27256649 TI - The Port Arthur massacre and the National Firearms Agreement: 20 years on, what are the lessons? AB - The 20th anniversary of the National Firearms Agreement (NFA) offers lessons for mental health and public health. Along with similar international legislation, the NFA exemplifies how firearms regulation can prevent firearm mortality and injuries. The gun lobby claims that mental illness underpins gun violence and should be a key site for intervention. A modest but significant link exists between mental disorders and community violence. However, the vast majority of mentally ill individuals are not violent. Despite media portrayals of their dangerousness, they are more likely to be victims of violence and of suicide. Most violent individuals do not have mental illness, and most mass murderers do not have identifiable severe mental illness. Many have maladaptive personality configurations. Gun availability and gun ownership, not severe mental illness, determines most gun homicides. Following recent gun massacres in the United States, there have been calls for better resourcing of mental health services to help identify and respond to those at risk and to regulate firearms access. Screening mentally ill populations for violence risk is misguided. However, clinicians can play a key role in working with legal authorities to monitor and assist regulation of firearm access, especially among high risk populations. Clinician involvement must be complemented by wider gun control measures. The gun lobby's turning the firearms availability debate into a question about whether people with mental illness histories should access such weapons is a calculated appeal to prejudice. PMID- 27256650 TI - A decade of Australian methotrexate dosing errors. AB - OBJECTIVE: Accidental daily dosing of methotrexate can result in life-threatening toxicity. We investigated methotrexate dosing errors reported to the National Coronial Information System (NCIS), the Therapeutic Goods Administration Database of Adverse Event Notifications (TGA DAEN) and Australian Poisons Information Centres (PICs). DESIGN AND SETTING: A retrospective review of coronial cases in the NCIS (2000-2014), and of reports to the TGA DAEN (2004-2014) and Australian PICs (2004-2015). Cases were included if dosing errors were accidental, with evidence of daily dosing on at least 3 consecutive days. MAIN OUTCOME MEASURES: Events per year, dose, consecutive days of methotrexate administration, reasons for the error, clinical features. RESULTS: Twenty-two deaths linked with methotrexate were identified in the NCIS, including seven cases in which erroneous daily dosing was documented. Methotrexate medication error was listed in ten cases in the DAEN, including two deaths. Australian PIC databases contained 92 cases, with a worrying increase seen during 2014-2015. Reasons for the errors included patient misunderstanding and incorrect packaging of dosette packs by pharmacists. The recorded clinical effects of daily dosage were consistent with those previously reported for methotrexate toxicity. CONCLUSION: Dosing errors with methotrexate can be lethal and continue to occur despite a number of safety initiatives in the past decade. Further strategies to reduce these preventable harms need to be implemented and evaluated. Recent suggestions include further changes in packet size, mandatory weekly dosing labelling on packaging, improving education, and including alerts in prescribing and dispensing software. PMID- 27256651 TI - Female representation at Australasian specialty conferences. PMID- 27256652 TI - Leslie Cowlishaw (1877-1943): the "bibliophile from the bush". PMID- 27256653 TI - Margaret Anne Burgess. PMID- 27256654 TI - High dependency. PMID- 27256655 TI - Multiparametric Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer: A Systematic Review. AB - A systematic review was conducted to investigate the use of multiparametric magnetic resonance imaging (MPMRI) followed by targeted biopsy in the diagnosis of clinically significant prostate cancer (CSPC) and to compare it with transrectal ultrasound-guided (TRUS-guided) systematic biopsy in patients with an elevated risk of prostate cancer who are either biopsy-naive or who have a previous negative TRUS-guided biopsy. MEDLINE, PubMed and EMBASE (1997 to April 2014), the Cochrane Library and six relevant conferences were searched to find eligible studies. Search terms indicative of 'prostate cancer' and 'magnetic resonance imaging' with their alternatives were used. Twelve systematic reviews, 52 full texts and 28 abstracts met the preplanned study selection criteria; data from 15 articles were extracted. In patients with an elevated risk of prostate cancer who were biopsy-naive, MPMRI followed by targeted biopsy could detect 2 13% of CSPC patients whom TRUS-guided systematic biopsy missed; TRUS-guided systematic biopsy could detect 0-7% of CSPC patients whom MPMRI followed by targeted biopsy missed. In patients with an elevated risk of prostate cancer who had a previous negative TRUS-guided biopsy, MPMRI followed by targeted biopsy detected more CSPC patients than repeated TRUS-guided systematic biopsy in all four studies, with a total of 516 patients, but only one study reached a statistically significant difference. In patients with an elevated risk of prostate cancer who are biopsy-naive, there is insufficient evidence for MPMRI followed by targeted biopsy to be considered the standard of care. In patients who had a prior negative TRUS-guided systematic biopsy and show a growing risk of having CSPC, MPMRI followed by targeted biopsy may be helpful to detect more CSPC cases as opposed to a repeat TRUS-guided systematic biopsy. PMID- 27256656 TI - Re: Fetal umbilical-portal-systemic venous shunt: in-utero classification and clinical significance. R. Achiron and Z. Kivilevitch. Ultrasound Obstet Gynecol 2016; 47: 739-747. PMID- 27256658 TI - Reply. PMID- 27256657 TI - Re: Placental magnetic resonance imaging T2* measurements in normal pregnancies and in those complicated by fetal growth restriction. M. Sinding, D. A. Peters, J. B. Frokjaer, O. B. Christiansen, A. Petersen, N. Uldbjerg and A. Sorensen. Ultrasound Obstet Gynecol 2016; 47: 748-754. PMID- 27256659 TI - Ductus venosus in twins: science matters. PMID- 27256660 TI - Re: Clinical implementation of routine screening for fetal trisomies in the UK NHS: cell-free DNA test contingent on results from first-trimester combined test. PMID- 27256661 TI - Reply. PMID- 27256662 TI - Spatial considerations during cryopreservation of a large volume sample. AB - There have been relatively few studies on the implications of the physical conditions experienced by cells during large volume (litres) cryopreservation - most studies have focused on the problem of cryopreservation of smaller volumes, typically up to 2 ml. This study explores the effects of ice growth by progressive solidification, generally seen during larger scale cryopreservation, on encapsulated liver hepatocyte spheroids, and it develops a method to reliably sample different regions across the frozen cores of samples experiencing progressive solidification. These issues are examined in the context of a Bioartificial Liver Device which requires cryopreservation of a 2 L volume in a strict cylindrical geometry for optimal clinical delivery. Progressive solidification cannot be avoided in this arrangement. In such a system optimal cryoprotectant concentrations and cooling rates are known. However, applying these parameters to a large volume is challenging due to the thermal mass and subsequent thermal lag. The specific impact of this to the cryopreservation outcome is required. Under conditions of progressive solidification, the spatial location of Encapsulated Liver Spheroids had a strong impact on post-thaw recovery. Cells in areas first and last to solidify demonstrated significantly impaired post-thaw function, whereas areas solidifying through the majority of the process exhibited higher post-thaw outcome. It was also found that samples where the ice thawed more rapidly had greater post-thaw viability 24 h post-thaw (75.7 +/- 3.9% and 62.0 +/- 7.2% respectively). These findings have implications for the cryopreservation of large volumes with a rigid shape and for the cryopreservation of a Bioartificial Liver Device. PMID- 27256663 TI - Perioperative changes in TGF-beta1 levels predict the oncological outcome of cryoablation-receiving patients with localized prostate cancer. AB - PURPOSE: To evaluate the cytokine transforming growth factor beta 1 (TGF-beta1) as a predictor of oncological outcomes in patients after cryoablation. MATERIALS AND METHODS: Perioperative blood samples from prostate cancer (PC) patients who underwent total gland cryoablation between October 2011 and March 2013 were collected prospectively. Plasma TGF-beta1 levels were quantified using magnetic bead immunoassay. The perioperative change in TGF-beta1 was defined as the change in TGF-beta1 from before surgery to 1-2 months after surgery. Biochemical recurrence (BCR) was defined according to the Phoenix criteria. The Mann-Whitney U, Kruskal-Wallis rank sum, and Chi-square test were used to compare the clinical characteristics of the subsets. The Cox proportional hazard model was applied for the comparison of recurrence risk among the groups. RESULTS: A total of 75 PC patients were included. During a median follow-up period of 12 months (range: 2.5 47 months), 11 patients had BCR, and 64 patients did not. Significantly greater changes in the perioperative TGF-beta1 levels (median: 470.3 vs. 78.9 pg/ml) were observed in patients with than without BCR (p < 0.05). According to the changes in TGF-beta1 levels, the patients were further divided into 4 groups, which were determined in the quartile categories of perioperative TGF-beta1 levels. Group 4 (>=430) predicted the worst BCR outcome. CONCLUSIONS: Perioperative plasma TGF beta1 levels were associated with BCR after prostate cryoablation for localized PC. Increase in postoperative plasma TGF-beta1 may be a novel predictor for poor oncological outcomes and prompt a more aggressive follow-up or earlier salvage treatment. PMID- 27256664 TI - Fertility and flow cytometry study of frozen-thawed sperm in cryopreservation medium supplemented with soybean lecithin. AB - Semen cryopreservation can provide genetic resources for a large number of females from a small number of superior males. Optimization of cryopreservation media to achieve the highest quality of post-thaw semen is crucial. Soybean lecithin has evaluated as a plant-based cryoprotectant for substitution of egg yolk in ram semen extender. Flow cytometric and fertility assessments were applied following cryopreservation procedure in two experimental groups (SL group: extender containing 1% w/v soybean lecithin and EY group: extender containing 20% v/v egg yolk). The higher percentage of live sperm and the lower percentage of dead sperm were obtained in SL (47.66 +/- 1.38, 52.33 +/- 1.69, respectively) extender compared to EY (41.16 +/- 1.38, 58.83 +/- 1.69). For motion characteristics, plasma membrane integrity, acrosome integrity and mitochondria activity, no significant difference was observed between SL and EY extenders. In artificial insemination experiment, there was no significant difference in pregnancy rate, lambing rate and twining rate between SL and EY extenders. It can be concluded that SL extender can be an efficient alternative extender to preserve ram sperm during cryopreservation procedure without adverse effects. PMID- 27256665 TI - IGF1 stabilizes sperm membrane proteins to reduce cryoinjury and maintain post thaw sperm motility in buffalo (Bubalus bubalis) spermatozoa. AB - Insulin like growth factor 1 (IGF1) in the seminal plasma is reported to improve sperm motility by reducing oxidative stress. The present study was conducted to assess the effect of addition of IGF1 on sperm function and protein composition during cryopreservation process. Semen samples were collected from six Murrah buffaloes (2 ejaculates from each animal) and diluted (80 million/ml) in tris egg yolk extender and divided into control, T1, T2 and T3, groups supplemented with 0, 50, 100 and 150 ng of IGF1/mL, respectively. The semen was filled in straws (250 MUL) and straws from each group were divided into two batches. One batch was processed for freezing and another batch was incubated at 4 degrees C for 4 h. The sperm kinematic and functional parameters were studied in both the batches. A significant (P < 0.05) positive effect of IGF1 was observed on functional membrane integrity (%) during incubation at 4 degrees C for 4 h in T3 as compared to control group. The spermatozoa (%) positive for structural membrane integrity, mitochondrial membrane potential and the metabolic activity in post thaw semen were significantly (P < 0.05) high in T3 than the control group. The acrosomal integrity was significantly (P < 0.05) higher in T2 group as compared to control. The proteins (kDa) of 17.3 with pI 4.2 (calmodulin), 11.3 with pI 6.5 (dermcidin) and 18.1 with pI 5.5 (sperm acrosome membrane associated protein3) were protected in IGF1 group. The study suggests that IGF1 can be added to the extender for improving cryosurvial of buffalo spermatozoa. PMID- 27256666 TI - Surgical extraction of canine oesophageal foreign bodies through a gastrotomy approach: 12 cases. AB - OBJECTIVE: To describe a gastrotomy approach to remove foreign bodies located in the caudal oesophagus. MATERIALS AND METHODS: Retrospective examination of case records of dogs with surgical management of foreign body located in the caudal oesophagus. RESULTS: Twelve dogs with caudal oesophageal foreign body were managed surgically after unsuccessful endoscopic approaches. The foreign body was successfully extracted via gastrotomy in all 12 cases. Ten dogs recovered well without any postoperative complications but one dog died during the immediate postoperative period and one during hospitalisation. CLINICAL RELEVANCE: Caudal oesophageal foreign body extraction by gastrotomy is a possible alternative to transthoracic oesophagotomy. Based on the small population presented here this approach performed through a laparotomy appears easy, with a low rate of perioperative and postoperative complications. PMID- 27256667 TI - Prospective, Multicenter Study of 5-Fluorouracil Therapeutic Drug Monitoring in Metastatic Colorectal Cancer Treated in Routine Clinical Practice. AB - BACKGROUND: Studies have demonstrated that body surface area-based dosing of chemotherapy drugs leads to significant individual exposure variability, with a substantial risk of under- or overdosing. The present study was initiated to validate the use of therapeutic drug management (TDM) to personalize 5 fluorouracil (5-FU) dosing in patients with metastatic colorectal cancer treated in routine clinical practice. PATIENTS AND METHODS: A total of 75 patients with metastatic colorectal cancer from 8 German medical centers received <= 6 administrations of infusional 5-FU according to the AIO (folinate, 5-FU; n = 16), FOLFOX6 (leucovorin calcium [folinic acid], 5-FU, and oxaliplatin; n = 26), or FUFOX (oxaliplatin plus 5-FU/folinic acid; n = 33) regimen. Initial infusional 5 FU dosing for all patients was determined by the BSA. Individual 5-FU exposure (area under the curve [AUC]) was measured using an immunoassay of a blood sample taken during each infusion. To achieve a target AUC of 20 to 30 mg * h/L, subsequent infusional 5-FU doses were adjusted according to the previous cycle's 5-FU AUC. The primary objective was to confirm that TDM of infusional 5-FU resulted in an increased proportion of patients in the target AUC range at the fourth versus the first administration. The secondary objective was to determine whether 5-FU TDM reduced the treatment-related toxicities compared with the historical data. RESULTS: The average 5-FU AUC at the first administration was 18 +/- 6 mg * h/L, with 64%, 33%, and 3% of the patients below, within, or above the target AUC range, respectively. By the fourth administration, the average 5-FU AUC was 25 +/- 7 mg * h/L (P < .001), with 54% of patients within the target 5-FU AUC range (P = .0294). The incidence of 5-FU-related grade 3 and 4 diarrhea (4.6%), nausea (3.4%), fatigue (0.0%), and mucositis (0.2%) was reduced compared with the historical data, despite 55% of the patients receiving increased doses. CONCLUSION: Personalization of 5-FU dosing using TDM in routine clinical practice resulted in significantly improved 5-FU exposure and suggested a lower incidence of 5-FU-related toxicities. PMID- 27256668 TI - Bevacizumab Efficacy Is Influenced by Primary Tumor Resection in First-Line Treatment of Metastatic Colorectal Cancer in a Retrospective Multicenter Study. AB - INTRODUCTION: There is no predictive factor of response to bevacizumab in metastatic colorectal cancer. Nevertheless, preclinical studies demonstrated an interaction between primary tumor and metastatic sites for the neoangiogenesis regulation. The primary objective of our study was to identify an effect of up front primary tumor resection (UPTR) on bevacizumab efficacy. PATIENTS AND METHODS: Between 2008 and 2010, we retrospectively analyzed progression-free survival (PFS) and overall survival (OS) of 316 patients with synchronous and metachronous metastatic colorectal cancer according to bevacizumab addition to first-line chemotherapy and UPTR. RESULTS: Among 206 patients with UPTR, the addition of bevacizumab to chemotherapy significantly improved OS compared to chemotherapy alone (29.8 vs. 23.9 months respectively; hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.40-0.83; P = .003). This effect was confirmed in multivariate analysis. There was also a nonsignificant trend toward improved PFS (9.7 vs. 8.4 months respectively; HR 0.71; 95% CI, 0.50-1.02; P = .062). Conversely, among 110 patients without UPTR, the addition of bevacizumab to chemotherapy had no effect on OS compared to chemotherapy alone (18.2 vs. 19.3 months respectively; HR 0.96; 95% CI, 0.65-1.42; P = .853). Bevacizumab significantly improved PFS (8.1 vs. 5.7 months respectively; HR 0.66; 95% CI, 0.45-0.96; P = .032) without confirmation in multivariate analysis. CONCLUSION: In this retrospective study, bevacizumab seems to improve OS only in patients with UPTR, which could suggest a complementarity of both therapeutic modalities for antiangiogenic effect. PMID- 27256669 TI - Letter by Kamtchum-Tatuene et al Regarding Article, "Mechanical Thrombectomy Improves Functional Outcomes Independent of Pretreatment With Intravenous Thrombolysis". PMID- 27256670 TI - Clinical Outcomes of Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study. AB - BACKGROUND AND PURPOSE: Preclinical data suggest that cell-based therapies have the potential to improve stroke outcomes. METHODS: Eighteen patients with stable, chronic stroke were enrolled in a 2-year, open-label, single-arm study to evaluate the safety and clinical outcomes of surgical transplantation of modified bone marrow-derived mesenchymal stem cells (SB623). RESULTS: All patients in the safety population (N=18) experienced at least 1 treatment-emergent adverse event. Six patients experienced 6 serious treatment-emergent adverse events; 2 were probably or definitely related to surgical procedure; none were related to cell treatment. All serious treatment-emergent adverse events resolved without sequelae. There were no dose-limiting toxicities or deaths. Sixteen patients completed 12 months of follow-up at the time of this analysis. Significant improvement from baseline (mean) was reported for: (1) European Stroke Scale: mean increase 6.88 (95% confidence interval, 3.5-10.3; P<0.001), (2) National Institutes of Health Stroke Scale: mean decrease 2.00 (95% confidence interval, 2.7 to -1.3; P<0.001), (3) Fugl-Meyer total score: mean increase 19.20 (95% confidence interval, 11.4-27.0; P<0.001), and (4) Fugl-Meyer motor function total score: mean increase 11.40 (95% confidence interval, 4.6-18.2; P<0.001). No changes were observed in modified Rankin Scale. The area of magnetic resonance T2 fluid-attenuated inversion recovery signal change in the ipsilateral cortex 1 week after implantation significantly correlated with clinical improvement at 12 months (P<0.001 for European Stroke Scale). CONCLUSIONS: In this interim report, SB623 cells were safe and associated with improvement in clinical outcome end points at 12 months. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01287936. PMID- 27256671 TI - Postmenopausal Hormone Therapy and Risk of Stroke: Impact of the Route of Estrogen Administration and Type of Progestogen. AB - BACKGROUND AND PURPOSE: The benefit/risk analysis of hormone therapy in postmenopausal women is not straightforward and depends on cardiovascular disease. Evidence supports the safety of transdermal estrogens and the importance of progestogens for thrombotic risk. However, the differential association of oral and transdermal estrogens with stroke remains poorly investigated. Furthermore, there are no data regarding the impact of progestogens. METHODS: We set up a nested case-control study of ischemic stroke (IS) within all French women aged 51 to 62 years between 2009 and 2011 without personal history of cardiovascular disease or contraindication to hormone therapy. Participants were identified using the French National Health Insurance database, which includes complete drug claims for the past 3 years and French National hospital data. We identified 3144 hospitalized IS cases who were matched for age and zip code to 12 158 controls. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Compared with nonusers, the adjusted ORs of IS were1.58 (95% CI, 1.01-2.49) in oral estrogen users and 0.83 (0.56-1.24) in transdermal estrogens users (P<0.01). There was no association of IS with use of progesterone (OR, 0.78; 95% CI, 0.49-1.26), pregnanes (OR, 1.00; 95% CI, 0.60-1.67), and nortestosterones (OR, 1.26; 95% CI, 0.62-2.58), whereas norpregnanes increased IS risk (OR, 2.25; 95% CI, 1.05-4.81). CONCLUSIONS: Both route of estrogen administration and progestogens were important determinants of IS. Our findings suggest that transdermal estrogens might be the safest option for short-term hormone therapy use. PMID- 27256673 TI - Response to Letter Regarding Article, "Mechanical Thrombectomy Improves Functional Outcomes Independent of Pretreatment With Intravenous Thrombolysis". PMID- 27256672 TI - Where to Focus Efforts to Reduce the Black-White Disparity in Stroke Mortality: Incidence Versus Case Fatality? AB - BACKGROUND AND PURPOSE: At age 45 years, blacks have a stroke mortality ~3* greater than their white counterparts, with a declining disparity at older ages. We assess whether this black-white disparity in stroke mortality is attributable to a black-white disparity in stroke incidence versus a disparity in case fatality. METHODS: We first assess if black-white differences in stroke mortality within 29 681 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort reflect national black-white differences in stroke mortality and then assess the degree to which black-white differences in stroke incidence or 30-day case fatality after stroke contribute to the disparities in stroke mortality. RESULTS: The pattern of stroke mortality within the study mirrors the national pattern, with the black-to-white hazard ratio of ~4.0 at age 45 years decreasing to ~1.0 at age 85 years. The pattern of black-to-white disparities in stroke incidence shows a similar pattern but no evidence of a corresponding disparity in stroke case fatality. CONCLUSIONS: These findings show that the black-white differences in stroke mortality are largely driven by differences in stroke incidence, with case fatality playing at most a minor role. Therefore, to reduce the black-white disparity in stroke mortality, interventions need to focus on prevention of stroke in blacks. PMID- 27256674 TI - Distinct mechanisms regulate Cdx2 expression in the blastocyst and in trophoblast stem cells. AB - The first intercellular differences during mammalian embryogenesis arise in the blastocyst, producing the inner cell mass and the trophectoderm. The trophectoderm is the first extraembryonic tissue and does not contribute to the embryo proper, its differentiation instead forming tissues that sustain embryonic development. Crucial roles in extraembryonic differentiation have been identified for certain transcription factors, but a comprehensive picture of the regulation of this early specification is still lacking. Here, we investigated whether the regulatory mechanisms involved in Cdx2 expression in the blastocyst are also utilized in the postimplantation embryo. We analyzed an enhancer that is regulated through Hippo and Notch in the blastocyst trophectoderm, unexpectedly finding that it is inactive in the extraembryonic structures at postimplantation stages. Further analysis identified other Cdx2 regulatory elements including a stem-cell specific regulatory sequence and an element that drives reporter expression in the trophectoderm, a subset of cells in the extraembryonic region of the postimplantation embryo and in trophoblast stem cells. The cross comparison in this study of cis-regulatory elements employed in the blastocyst, stem cell populations and the postimplantation embryo provides new insights into early mammalian development and suggests a two-step mechanism in Cdx2 regulation. PMID- 27256675 TI - Magnolol pretreatment attenuates heat stress-induced IEC-6 cell injury. AB - OBJECTIVE: Heat stress (HS) is an important environmental stressor that adversely influences livestock during the summer. The aim of this study was to investigate whether magnolol protects against HS-induced intestinal epithelial cell injury. MATERIALS AND METHODS: An intestinal epithelial cell line (IEC-6) was subjected to HS at 42 degrees C, with and without magnolol pretreatment. Cell injury was detected by monitoring lactate dehydrogenase (LDH) release. MTS (3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium) assay was used to assess cell proliferation and viability, including identifying effective concentrations of magnolol. Flow cytometry confirmed G1 phase cell-cycle arrest and its alleviation by magnolol. Active DNA synthesis was measured by incorporation of nucleic acid 5-ethynyl-2'-deoxyuridine (EdU). G1 phase cell-cycle-related gene expression was assessed by real-time reverse transcription polymerase chain reaction (RT-PCR) and levels of G1-phase-related proteins by Western blotting. RESULTS: HS induced IEC-6 cell injury and decreased cell viability, as demonstrated by data from LDH and MTS assays, respectively. Based on a number of criteria, IEC-6 cells subjected to HS were arrested in the G1 phase of the cell cycle. Magnolol pretreatment decreased HS-induced cell injury through relief of this cell-cycle arrest. CONCLUSIONS: Magnolol pretreatment attenuates HS-induced injury in IEC-6 cells. Magnolol is potentially promising as a protective strategy for HS in livestock. PMID- 27256676 TI - Inhibitory effect of Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts on lipopolysaccharide-stimulated inflammatory response in RAW 264.7 cells. AB - Blueberries are a rich source of anthocyanins, which are associated with health benefits contributing to a reduced risk for many diseases. The present study identified the functional Gardenblue blueberry (Vaccinium ashei Reade) anthocyanin extracts (GBBAEs) and evaluated their capacity and underlying mechanisms in protecting murine RAW 264.7 cells from lipopolysaccharide (LPS) stimulated inflammation in vitro. Enzyme-linked immunosorbent assay (ELISA) kit results showed that GBBAEs significantly inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), IL-1beta, and interferon gamma (INF-gamma). Real-time polymerase chain reaction (PCR) analysis indicated that the mRNA expression levels of IL-6, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and cyclooxygenase 2 (COX-2) were suppressed in LPS-stimulated RAW 264.7 cells. Additionally, Western blot analysis was used to evaluate the relative protein expression levels of COX 2 and nuclear factor-kappaB p65 (NF-kappaBp65). All these results suggested the potential use of GBBAEs as a functional food for the treatment of inflammatory diseases. PMID- 27256678 TI - Apigenin-7-O-beta-D-glycoside isolation from the highly copper-tolerant plant Elsholtzia splendens. AB - Elsholtzia splendens (Lamiaceae) is a copper-tolerant plant species growing on copper deposits in the south of China. Chromatographic separation of n-BuOH extracts from the flowering aerial biomass afforded apigenin-7-O-beta-D glycoside, using macroporous resin, SephadexTM LH-20 gel, polyamide resin as well as preparative high-performance liquid chromatography (P-HPLC) columns. Chemical structure was elucidated using HPLC/ESI-MS (electrospray ionization-mass spectrometry), Fourier transform infrared (FTIR), and (1)D- and (2)D-nuclear magnetic resonance (NMR). Apigenin-7-O-beta-D-glycoside could be the post harvesting product from E. splendens biomass. PMID- 27256677 TI - Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice. AB - BACKGROUND: Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. OBJECTIVE: This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. RESULTS: Administration of myricetin dramatically reduced the body weight of diet induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-alpha (TNF-alpha)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD induced obesity in mice appeared to be partially mediated through the down regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). CONCLUSIONS: Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications. PMID- 27256679 TI - Characterization of beta-glucosidase from Aspergillus terreus and its application in the hydrolysis of soybean isoflavones. AB - An extracellular beta-glucosidase produced by Aspergillus terreus was identified, purified, characterized and was tested for the hydrolysis of soybean isoflavone. Matrix-assisted laser desorption/ionization with tandem time-of-flight/time-of flight mass spectrometry (MALDI-TOF/TOF MS) revealed the protein to be a member of the glycosyl hydrolase family 3 with an apparent molecular mass of about 120 kDa. The purified beta-glucosidase showed optimal activity at pH 5.0 and 65 degrees C and was very stable at 50 degrees C. Moreover, the enzyme exhibited good stability over pH 3.0-8.0 and possessed high tolerance towards pepsin and trypsin. The kinetic parameters Km (apparent Michaelis-Menten constant) and Vmax (maximal reaction velocity) for p-nitrophenyl-beta-D-glucopyranoside (pNPG) were 1.73 mmol/L and 42.37 U/mg, respectively. The Km and Vmax for cellobiose were 4.11 mmol/L and 5.7 U/mg, respectively. The enzyme efficiently converted isoflavone glycosides to aglycones, with a hydrolysis rate of 95.8% for daidzin, 86.7% for genistin, and 72.1% for glycitin. Meanwhile, the productivities were 1.14 mmol/(L.h) for daidzein, 0.72 mmol/(L.h) for genistein, and 0.19 mmol/(L.h) for glycitein. This is the first report on the application of A. terreus beta glucosidase for converting isoflavone glycosides to their aglycones in soybean products. PMID- 27256680 TI - Molecularly imprinted polymers as the extracted sorbents of clenbuterol ahead of liquid chromatographic determination. AB - A pre-treatment methodology for clenbuterol hydrochloride (CLEN) isolation and enrichment in a complex matrix environment was developed through exploiting molecularly imprinted polymers (MIPs). CLEN-imprinted polymers were synthesized by the combined use of ally-beta-cyclodextrin (ally-beta-CD) and methacrylic acid (MAA), allyl-beta-CD and acrylonitrile (AN), and allyl-beta-CD and methyl methacrylate (MMA) as the binary functional monomers. MAA-linked allyl-beta-CD MIPs (M-MAA) were characterized by Fourier transform-infrared (FT-IR) spectroscopy and a scanning electron microscope (SEM). Based upon the results, M MAA polymers generally proved to be an excellent selective extraction compared to its references: AN-linked allyl-beta-CD MIPs (M-AN) and MMA-linked allyl-beta-CD MIPs (M-MMA). M-MAA polymers were eventually chosen to run through a molecularly imprinted solid-phase extraction (MISPE) micro-column to enrich CLEN residues spiked in pig livers. A high recovery was achieved, ranging from 91.03% to 96.76% with relative standard deviation (RSD) <=4.45%. PMID- 27256681 TI - Evaluation of the major royal jelly proteins as an alternative to fetal bovine serum in culturing human cell lines. AB - Royal jelly (RJ) is a well-known bioactive substance. It contains large amounts of major royal jelly proteins (MRJPs), which express growth-factor-like activity in several animal and human cell lines. However, the question on whether MRJPs possess growth-factor-like activity on all types of cell cultures remains. In order to determine whether MRJPs can be used as an alternative to fetal bovine serum (FBS) in different types of human cell culture, the proliferation of the complex serum with different ratios of MRJPs/FBS (M/F) was evaluated on five cell lines: 293T, HFL-I, 231, HCT116, and Changliver using MTT (3-(4,5-dimethyl-2 thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The proliferation activity of the combination of the complex M/F serum with cytokines on the test cell lines was also measured. The results demonstrated that the complex serum with M/F 6/4 possessed the highest proliferation activity similar to or in excess of FBS. However, no activity of complex medium with M/F 6/4 was observed in 231 cells, indicating a selectivity of MRJPs on cell types. Compared with the complex medium with M/F 6/4, the complex medium with M/F 6/4 together with two cytokines, epidermal growth factor (EGF) and insulin-transferrin-selenium (ITS), promoted proliferations of Changliver, 293T, HCT116, and HFL-I by 18.73%-56.19% (P<0.01). Our findings demonstrate that MRJPs could partially replace FBS in culturing many human cell lines. PMID- 27256682 TI - Investigation of absorption and scattering characteristics of kiwifruit tissue using a single integrating sphere system. AB - For a quantitative understanding of light interaction with fruit tissue, it is critical to obtain two fundamental parameters: the absorption coefficient and the scattering coefficient of the tissue. This study was to investigate the optical properties of kiwifruit tissue at the wavelength of 632.8 nm. The total reflectance and total transmittance of kiwifruit tissue from three parts (including the flesh part, the seed part, and the seed-base part) were measured using a single integrating sphere system. Based on the measured spectral signals, the absorption coefficient MUa and the reduced scattering coefficient MUs' of kiwifruit tissue were calculated using the inverse adding-doubling (IAD) method. Phantoms made from Intralipid 20% and India ink as well as a Biomimic solid phantom were used for system validation. The mean values of MUa and MUs' of different parts of the kiwifruit were 0.031-0.308 mm(-1) and 0.120-0.946 mm(-1), respectively. The results showed significant differences among the MUa and MUs' of the three parts of the kiwifruit. The results of this study confirmed the importance of studying the optical properties for a quantitative understanding of light interaction with fruit tissue. Further investigation of fruit optical properties will be extended to a broader spectral region and different kinds of fruits. PMID- 27256683 TI - Meta-Analysis of Genome-Wide Association Studies with Correlated Individuals: Application to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). AB - Investigators often meta-analyze multiple genome-wide association studies (GWASs) to increase the power to detect associations of single nucleotide polymorphisms (SNPs) with a trait. Meta-analysis is also performed within a single cohort that is stratified by, e.g., sex or ancestry group. Having correlated individuals among the strata may complicate meta-analyses, limit power, and inflate Type 1 error. For example, in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), sources of correlation include genetic relatedness, shared household, and shared community. We propose a novel mixed-effect model for meta-analysis, "MetaCor," which accounts for correlation between stratum-specific effect estimates. Simulations show that MetaCor controls inflation better than alternatives such as ignoring the correlation between the strata or analyzing all strata together in a "pooled" GWAS, especially with different minor allele frequencies (MAFs) between strata. We illustrate the benefits of MetaCor on two GWASs in the HCHS/SOL. Analysis of dental caries (tooth decay) stratified by ancestry group detected a genome-wide significant SNP (rs7791001, P-value = 3.66*10-8, compared to 4.67*10-7 in pooled), with different MAFs between strata. Stratified analysis of body mass index (BMI) by ancestry group and sex reduced overall inflation from lambdaGC=1.050 (pooled) to lambdaGC=1.028 (MetaCor). Furthermore, even after removing close relatives to obtain nearly uncorrelated strata, a naive stratified analysis resulted in lambdaGC=1.058 compared to lambdaGC=1.027 for MetaCor. PMID- 27256684 TI - Evaluating the Impact of Parent-Reported Medical Home Status on Children's Health Care Utilization, Expenditures, and Quality: A Difference-in-Differences Analysis with Causal Inference Methods. AB - OBJECTIVE: To evaluate the effects of the parent-reported medical home status on health care utilization, expenditures, and quality for children. DATA SOURCES: Medical Expenditure Panel Survey (MEPS) during 2004-2012, including a total of 9,153 children who were followed up for 2 years in the survey. STUDY DESIGN: We took a causal difference-in-differences approach using inverse probability weighting and doubly robust estimators to study how changes in medical home status over a 2-year period affected children's health care outcomes. Our analysis adjusted for children's sociodemographic, health, and insurance statuses. We conducted sensitivity analyses using alternative statistical methods, different approaches to outliers and missing data, and accounting for possible common-method biases. PRINCIPAL FINDINGS: Compared with children whose parents reported having medical homes in both years 1 and 2, those who had medical homes in year 1 but lost them in year 2 had significantly lower parent reported ratings of health care quality and higher utilization of emergency care. Compared with children whose parents reported having no medical homes in both years, those who did not have medical homes in year 1 but gained them in year 2 had significantly higher ratings of health care quality, but no significant differences in health care expenditures and utilization. CONCLUSIONS: Having a medical home may help improve health care quality for children; losing a medical home may lead to higher utilization of emergency care. PMID- 27256685 TI - Unhealthy diets, obesity and time discounting: a systematic literature review and network analysis. AB - There is an increasing policy commitment to address the avoidable burdens of unhealthy diet, overweight and obesity. However, to design effective policies, it is important to understand why people make unhealthy dietary choices. Research from behavioural economics suggests a critical role for time discounting, which describes how people's value of a reward, such as better health, decreases with delay to its receipt. We systematically reviewed the literature on the relationship of time discounting with unhealthy diets, overweight and obesity in Web of Science and PubMed. We identified 41 studies that met our inclusion criteria as they examined the association between time discount rates and (i) unhealthy food consumption; (ii) overweight and (iii) response to dietary and weight loss interventions. Nineteen out of 25 cross-sectional studies found time discount rates positively associated with overweight, obesity and unhealthy diets. Experimental studies indicated that lower time discounting was associated with greater weight loss. Findings varied by how time discount rates were measured; stronger results were observed for food than monetary-based measurements. Network co-citation analysis revealed a concentration of research in nutrition journals. Overall, there is moderate evidence that high time discounting is a significant risk factor for unhealthy diets, overweight and obesity and may serve as an important target for intervention. (c) 2016 The Authors Obesity Reviews published by John Wiley & Sons Ltd on behalf of International Association for the Study of Obesity (IASO). PMID- 27256686 TI - PLGA-linked alendronate enhances bone repair in diaphysis defect model. AB - Alendronate (ALN) is known as an anti-resorptive drug for the treatment of osteoporosis. Recently, ALN was found to stimulate osteogenic differentiation in mesenchymal stem cells and enhance new bone formation in calvarial bone defects. Previous in vitro and in vivo studies found that the effective concentration of ALN was approximately 1-10 MUm. In the present study, a poly (lactic-co glycolic acid) (PLGA) cross-linked ALN (PLGA-ALN) with a short-term controlled release property for local application to enhance bone repair was developed. An in vitro drug-release kinetic test showed that PLGA-ALN microspheres released an effective concentration (50-100 nm) of ALN for 9 days. The effect of PLGA-ALN on bone repair was tested in a rat femoral bone defect model. The biomechanical study results showed that the maximal strength, stiffness and energy absorption were significantly increased in the PLGA-ALN group compared with the PLGA group. The microstructure of the newly formed bone at the defect site was analysed using microcomputed tomography. The PLGA-ALN group significantly improved the trabecular bone volume at the defect site compared with the PLGA group. The fibril collagen and immunolocalized bone morphogenetic protein 2 were evident in the newly formed trabecular bone in the PLGA-ALN group. Local use of newly developed PLGA-ALN-enhanced bone repair was attributable to increasing bone matrix formation, which improved the ultrastructure of the newly formed bone and thus increased the biomechanical properties of the repaired bone. It is suggested that PLGA-ALN may be a potential bone graft substitute to enhance bone repair. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27256687 TI - Chronic orbital and calvarial fungal infection with Apophysomyces variabilis in an immunocompetent patient. AB - Apophysomyces is a rare fungal organism causing rhino-orbito-cerebral mycotic infections with high morbidity and mortality, typically in immunocompetent individuals. Several cases of Apophysomyces elegans orbital disease have been reported. Herein, we report a case of Apophysomyces variabilis infection involving the orbit, sinuses, and calvarium in an immunocompetent 74-year-old woman, with a review of the literature. Unlike prior cases of A. elegans classic rhino-orbito-cerebral infection, our case included diffuse calvarial lytic lesions and overlying soft tissue nodules, but without parenchymal intracranial involvement. There was radiographic and clinical evidence of infarction of the orbital contents and cavernous sinus thrombosis. Anastomoses between the superior orbital (ophthalmic) vein and diploic veins of the calvarium are believed to be primarily responsible for the unusual mode of spread on the extradural surface of the brain. Although the patient stabilized without definitive surgical intervention, her disease slowly and intermittently progressed for over a year after presentation, requiring multiple courses of antifungal treatment. PMID- 27256688 TI - Bilateral ocular panadnexal mass as initial presentation of systemic blastoid variant of mantle-cell lymphoma. AB - A 66-year-old man developed a slowly enlarging, bilateral, painless, periorbital, and orbital swelling with ptosis, nonaxial proptosis, chemosis, exposure keratopathy, and decreased vision in both eyes. He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma. A transpalpebral incisional biopsy revealed a rare case of mantle-cell lymphoma of blastoid variant, stage IVB. The main immunophenotype characteristics were cyclin D1+, CD5+, CD10-, CD23 , Bcl-6-/+, and a high (up to 80%) Ki-67 proliferation index. Following an excellent response to the immune-chemotherapy treatment plan, all ocular adnexal lymphoma manifestations disappeared completely; however, 13 months after the initial presentation, there was a recurrence of the disease with rapid worsening and death. The blastoid variant of mantle cell lymphoma, a rare subtype of mantle cell lymphoma, is a highly aggressive neoplasm, ultimately having a fatal outcome. As the initial manifestation of the disease, ocular adnexal region blastoid variant of mantle-cell lymphoma is an exceptional event, with only one previous case reported. PMID- 27256689 TI - Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species. AB - Lipid droplets (LDs) are organelles that contribute to various cellular functions that are vital for life. Aside from acting as a neutral lipid storage depot, they are also involved in building new membranes, synthesis of steroid hormones, and cell signaling. Many aspects of LD structure and function are not yet well understood. Here we investigate the interaction of perilipin 3, a member of the perilipin family of LD binding proteins, and three N-terminal truncation mutants with lipid monolayers. The interaction is studied as a function of surface pressure for a series of systematically chosen lipids. We find that the C terminus of perilipin 3 has different insertion behavior from that of the longer truncation mutants and the full-length protein. Inclusion of N-terminal sequences with the C terminus decreases the ability of the protein construct to insert in lipid monolayers. Coupling of anionic lipids to negative spontaneous curvature facilitates protein interaction and insertion. The C terminus shows strong preference for lipids with more saturated fatty acids. This work sheds light on the LD binding properties and function of the different domains of perilipin 3. PMID- 27256690 TI - Quantitative profiling of the endonuclear glycerophospholipidome of murine embryonic fibroblasts. AB - A reliable method for purifying envelope-stripped nuclei from immortalized murine embryonic fibroblasts (iMEFs) was established. Quantitative profiling of the glycerophospholipids (GPLs) in envelope-free iMEF nuclei yields several conclusions. First, we find the endonuclear glycerophospholipidome differs from that of bulk membranes, and phosphatidylcholine (PtdCho) and phosphatidylethanolamine species are the most abundant endonuclear GPLs by mass. By contrast, phosphatidylinositol (PtdIns) represents a minor species. We also find only a slight enrichment of saturated versus unsaturated GPL species in iMEF endonuclear fractions. Moreover, much lower values for GPL mass were measured in the iMEF nuclear matrix than those reported for envelope-stripped IMF-32 nuclei. The collective results indicate that the nuclear matrix in these cells is a GPL poor environment where GPL occupies only approximately 0.1% of the total nuclear matrix volume. This value suggests GPL accommodation in this compartment can be satisfied by binding to resident proteins. Finally, we find no significant role for the PtdIns/PtdCho-transfer protein, PITPalpha, in shuttling PtdIns into the iMEF nuclear matrix. PMID- 27256692 TI - Hirshfeld and DFT analysis of the N-heterocyclic carbene proligand methylenebis(N butylimidazolium) as the acetonitrile-solvated diiodide salt. AB - N-Heterocyclic carbene (NHC) based systems are usually exploited in the exploration of catalytic mechanisms and processes in organocatalysis, and homo- and heterogeneous catalysis. However, their molecular structures have not received adequate attention. The NHC proligand methylenebis(N-butylimidazolium) has been synthesized as the acetonitrile solvate of the diiodide salt, C15H26N4(2+).2I(-).CH3CN [1,1'-methylenebis(3-butylimidazolium) diiodide acetonitrile monosolvate], and fully characterized. An interesting cation-anion connection pattern has been identified in the crystal lattice, in which three iodide anions interact simultaneously with the cisoid-oriented cation. A Hirshfeld surface analysis reveals the predominance of hydrogen bonding over anion-pi interactions. This particular arrangement is observed in different methylene-bridged bis(imidazolium) cations bearing chloride or bromide counter anions. Density functional theory (DFT) calculations with acetonitrile as solvent reproduce the geometry of the title cation. PMID- 27256693 TI - Two tautomeric forms of 2-amino-5,6-dimethylpyrimidin-4-one. AB - Derivatives of 4-hydroxypyrimidine are an important class of biomolecules. These compounds can undergo keto-enol tautomerization in solution, though a search of the Cambridge Structural Database shows a strong bias toward the 3H-keto tautomer in the solid state. Recrystallization of 2-amino-5,6-dimethyl-4 hydroxypyrimidine, C6H9N3O, from aqueous solution yielded triclinic crystals of the 1H-keto tautomer, denoted form (I). Though not apparent in the X-ray data, the IR spectrum suggests that small amounts of the 4-hydroxy tautomer are also present in the crystal. Monoclinic crystals of form (II), comprised of a 1:1 ratio of both the 1H-keto and the 3H-keto tautomers, were obtained from aqueous solutions containing uric acid. Forms (I) and (II) exhibit one-dimensional and three-dimensional hydrogen-bonding motifs, respectively. PMID- 27256691 TI - Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved. AB - Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. "Stimulated by retinoic acid 6" (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor alpha, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFbeta1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1(-/-) mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease. PMID- 27256694 TI - Purine 3':5'-cyclic nucleotides with the nucleobase in a syn orientation: cAMP, cGMP and cIMP. AB - Purine 3':5'-cyclic nucleotides are very well known for their role as the secondary messengers in hormone action and cellular signal transduction. Nonetheless, their solid-state conformational details still require investigation. Five crystals containing purine 3':5'-cyclic nucleotides have been obtained and structurally characterized, namely adenosine 3':5'-cyclic phosphate dihydrate, C10H12N5O6P.2H2O or cAMP.2H2O, (I), adenosine 3':5'-cyclic phosphate 0.3-hydrate, C10H12N5O6P.0.3H2O or cAMP.0.3H2O, (II), guanosine 3':5'-cyclic phosphate pentahydrate, C10H12N5O7P.5H2O or cGMP.5H2O, (III), sodium guanosine 3':5'-cyclic phosphate tetrahydrate, Na(+).C10H11N5O7P(-).4H2O or Na(cGMP).4H2O, (IV), and sodium inosine 3':5'-cyclic phosphate tetrahydrate, Na(+).C10H10N4O7P( ).4H2O or Na(cIMP).4H2O, (V). Most of the cyclic nucleotide zwitterions/anions [two from four cAMP present in total in (I) and (II), cGMP in (III), cGMP(-) in (IV) and cIMP(-) in (V)] are syn conformers about the N-glycosidic bond, and this nucleobase arrangement is accompanied by Crib-H...Npur hydrogen bonds (rib = ribose and pur = purine). The base orientation is tuned by the ribose pucker. An analysis of data obtained from the Cambridge Structural Database made in the context of syn-anti conformational preferences has revealed that among the syn conformers of various purine nucleotides, cyclic nucleotides and dinucleotides predominate significantly. The interactions stabilizing the syn conformation have been indicated. The inter-nucleotide contacts in (I)-(V) have been systematized in terms of the chemical groups involved. All five structures display three dimensional hydrogen-bonded networks. PMID- 27256695 TI - A new one-dimensional Cd(II) coordination polymer with a two-dimensional layered structure incorporating 2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole and benzene 1,2-dicarboxylate ligands. AB - The N-heterocyclic ligand 2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole (imb) has a rich variety of coordination modes and can lead to polymers with intriguing structures and interesting properties. In the coordination polymer catena poly[[cadmium(II)-bis[MU-benzene-1,2-dicarboxylato-kappa(4)O(1),O(1'):O(2),O(2')] cadmium(II)-bis{MU-2-[(1H-imidazol-1-yl)methyl]-1H-benzimidazole} kappa(2)N(2):N(3);kappa(2)N(3):N(2)] dimethylformamide disolvate], {[Cd(C8H4O4)(C11H10N4)].C3H7NO}n, (I), each Cd(II) ion exhibits an irregular octahedral CdO4N2 coordination geometry and is coordinated by four O atoms from two symmetry-related benzene-1,2-dicarboxylate (1,2-bdic(2-)) ligands and two N atoms from two symmetry-related imb ligands. Two Cd(II) ions are connected by two benzene-1,2-dicarboxylate ligands to generate a binuclear [Cd2(1,2-bdic)2] unit. The binuclear units are further connected into a one-dimensional chain by pairs of bridging imb ligands. These one-dimensional chains are further connected through N-H...O hydrogen bonds and pi-pi interactions, leading to a two dimensional layered structure. The dimethylformamide solvent molecules are organized in dimeric pairs via weak interactions. In addition, the title polymer exhibits good fluorescence properties in the solid state at room temperature. PMID- 27256696 TI - Synthesis, crystal structure and antifungal activity of a divalent cobalt(II) complex with uniconazole. AB - Azole compounds have attracted commercial interest due to their high bactericidal and plant-growth-regulating activities. Uniconazole [or 1-(4-chlorophenyl)-4,4 dimethyl-2-(1H-1,2,4-triazol-1-yl)pent-1-en-3-ol] is a highly active 1,2,4 triazole fungicide and plant-growth regulator with low toxicity. The pharmacological and toxicological properties of many drugs are modified by the formation of their metal complexes. Therefore, there is much interest in exploiting the coordination chemistry of triazole pesticides and their potential application in agriculture. However, reports of complexes of uniconazole are rare. A new cobalt(II) complex of uniconazole, namely dichloridotetrakis[1-(4 chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl-kappaN(4))pent-1-en-3 ol]cobalt(II), [CoCl2(C15H18ClN3O)4], was synthesized and structurally characterized by element analysis, IR spectrometry and X-ray single-crystal diffraction. The crystal structural analysis shows that the Co(II) atom is located on the inversion centre and is coordinated by four uniconazole and two chloride ligands, forming a distorted octahedral geometry. The hydroxy groups of an uniconazole ligands of adjacent molecules form hydrogen bonds with the axial chloride ligands, resulting in one-dimensional chains parallel to the a axis. The complex was analysed for its antifungal activity by the mycelial growth rate method. It was revealed that the antifungal effect of the title complex is more pronounced than the effect of fungicide uniconazole for Botryosphaeria ribis, Wheat gibberellic and Grape anthracnose. PMID- 27256697 TI - Structural and spectroscopic characterization of two new blue luminescent pyridylbenzimidazole zinc(II) complexes. AB - Luminescent metal complexes are used in photooptical devices. Zinc(II) complexes are of interest because of the ability to tune their color, their high thermal stability and their favorable carrier transport character. In particular, some zinc(II) complexes with aryl diimine and/or heterocyclic ligands have been shown to emit brightly in the blue region of the spectrum. Zinc(II) complexes bearing derivatized imidazoles have been explored for possible optoelectronic applications. The structures of two zinc(II) complexes of 5,6-dimethyl-2-(pyridin 2-yl)-1-[(pyridin-2-yl)methyl]-1H-benzimidazole (L), namely dichlorido(dimethylformamide-kappaO){5,6-dimethyl-2-(pyridin-2-yl-kappaN)-1 [(pyridin-2-yl)methyl]-1H-benzimidazole-kappaN(3)}zinc(II) dimethylformamide monosolvate, [ZnCl2(C20H18N4)(C3H7NO)].C3H7NO, (I), and bis(acetato kappa(2)O,O'){5,6-dimethyl-2-(pyridin-2-yl-kappaN)-1-[(pyridin-2-yl)methyl]-1H benzimidazole-kappaN(3)}zinc(II) ethanol monosolvate, [Zn(C2H3O2)2(C20H18N4)].C2H5OH, (II), are reported. Complex (I) crystallized as a dimethylformamide solvate and exhibits a distorted trigonal bipyramidal coordination geometry. The coordination sphere consists of a bidentate L ligand spanning axial to equatorial sites, two chloride ligands in equatorial sites, and an O-bound dimethylformamide ligand in the remaining axial site. The other complex, (II), crystallized as an ethanol solvate. The Zn(II) atom has a distorted trigonal prismatic coordination geometry, with two bidentate acetate ligands occupying two edges and a bidentate L ligand occupying the third edge of the prism. Complexes (I) and (II) emit in the blue region of the spectrum. The results of density functional theory (DFT) calculations suggest that the luminescence of L results from pi*<-pi transitions and that the luminescence of the complexes results from interligand charge-transfer transitions. The orientation of the 2-(pyridin-2-yl) substituent with respect to the benzimidazole system was found to have an impact on the calculated HOMO-LUMO gap (HOMO is highest occupied molecular orbital and LUMO is lowest unoccupied molecular orbital). PMID- 27256698 TI - Synthesis and crystal structures of C24-epimeric 20(R)-ocotillol-type saponins. AB - Ocotillol-type saponins have a wide spectrum of biological activities. Previous studies indicated that the configuration at the C24 position may be responsible for their stereoselectivity in pharmacological action and pharmacokinetics. Natural ocotillol-type saponins share a 20(S)-form but it has been found that the 20(R)-stereoisomers have different pharmacological effects. The semisynthesis of 20(R)-ocotillol-type saponins has not been reported and it is therefore worthwhile clarifying their crystal structures. Two C24 epimeric 20(R)-ocotillol type saponins, namely (20R,24S)-20,24-epoxydammarane-3beta,12beta,25-triol, C30H52O4, (III), and (20R,24R)-20,24-epoxydammarane-3beta,12beta,25-triol monohydrate, C30H52O4.H2O, (IV), were synthesized, and their structures were elucidated by spectral studies and finally confirmed by single-crystal X-ray diffraction. The (Me)C-O-C-C(OH) torsion angle of (III) is 146.41 (14) degrees , whereas the corresponding torsion angle of (IV) is -146.4 (7) degrees , indicating a different conformation at the C24 position. The crystal stacking in (III) generates an R4(4)(8) motif, through which the molecules are linked into a one-dimensional double chain. The chains are linked via nonclassical C-H...O hydrogen bonds into a two-dimensional network, and further stacked into a three dimensional structure. In contrast to (III), epimer (IV) crystallizes as a hydrate, in which the water molecules act as hydrogen-bond donors linking one dimensional chains into a two-dimensional network through intermolecular O-H...O hydrogen bonds. The hydrogen-bonded chains extend helically along the crystallographic a axis and generate a C4(4)(8) motif. PMID- 27256699 TI - Highly functionalized alkenes produced from base-free organocatalytic Wittig reactions: (E)-3-benzylidenepyrrolidine-2,5-dione, (E)-3-benzylidene-1 methylpyrrolidine-2,5-dione and (E)-3-benzylidene-1-tert-butylpyrrolidine-2,5 dione. AB - The Wittig reaction is a fundamental transformation for the preparation of alkenes from carbonyl compounds and phosphonium ylides. The ylides are prepared prior to the olefination step from the respective phosphonium salts by deprotonation utilizing strong bases. A first free-base catalytic Wittig reaction for the preparation of highly functionalized alkenes was based on tributylphosphane as the catalyst. Subsequently we developed a system employing a phospholene oxide as a pre-catalyst and trimethoxysilane as reducing agent which operates under milder conditions. The title compounds, (E)-3 benzylidenepyrrolidine-2,5-dione, C11H9NO2, (I), the methylpyrrolidine derivative, C12H11NO2, (II), and the tert-butylpyrrolidine derivative, C15H17NO2, (III), have been synthesized by base-free catalytic Wittig reactions. In the crystal of (I), molecules are linked into centrosymmetric dimers via pairs of N H...O hydrogen bonds. Furthermore, in the crystal structure of (III), there are two molecules in the asymmetric unit, whereas in (I) and (II), only one molecule is present. PMID- 27256700 TI - LMO2 and IL2RG synergize in thymocytes to mimic the evolution of SCID-X1 gene therapy-associated T-cell leukaemia. PMID- 27256701 TI - Response to 'PET after response to R-CHOP in primary mediastinal large B-cell lymphoma'. PMID- 27256703 TI - Altering Emulsion Stability with Heterogeneous Surface Wettability. AB - Emulsions-liquid droplets dispersed in another immiscible liquid-are widely used in a broad spectrum of applications, including food, personal care, agrochemical, and pharmaceutical products. Emulsions are also commonly present in natural crude oil, hampering the production and quality of petroleum fuels. The stability of emulsions plays a crucial role in their applications, but controlling the stability without external driving forces has been proven to be difficult. Here we show how heterogeneous surface wettability can alter the stability and dynamics of oil-in-water emulsions, generated by a co-flow microfluidic device. We designed a useful methodology that can modify a micro-capillary of desired heterogeneous wettability (e.g., alternating hydrophilic and hydrophobic regions) without changing the hydraulic diameter. We subsequently investigated the effects of flow rates and heterogeneous wettability on the emulsion morphology and motion. The experimental data revealed a universal critical timescale of advective emulsions, above which the microfluidic emulsions remain stable and intact, whereas below they become adhesive or inverse. A simple theoretical model based on a force balance can be used to explain this critical transition of emulsion dynamics, depending on the droplet size and the Capillary number-the ratio of viscous to surface effects. These results give insight into how to control the stability and dynamics of emulsions in microfluidics with flow velocity and different wettability. PMID- 27256704 TI - Reduction of Candida tropicalis biofilm by photoactivation of a Heterophyllaea pustulata extract. AB - CONTEXT: Biofilm formation is an important problem, since this growth mode confers resistance to drugs usually used in therapeutics. OBJECTIVE: In vitro antifungal activity of extracts obtained from Heterophyllaea pustulata Hook f. (Rubiaceae) were studied against Candida tropicalis biofilms, evaluating the effect of irradiation and the oxidative and nitrosative stresses as possible mechanisms of action. MATERIALS AND METHODS: Hexane, benzene, ethyl acetate and ethanol extracts were evaluated at three concentrations (0.2, 0.1 and 0.05 mg/mL) over mature biofilm, under darkness and irradiation. After 48 h of incubation, biofilm quantitation was performed by the O'Toole and Kolter method. Reactive oxygen species (ROS) was measured by nitro-blue tetrazolium (NBT) reaction and reactive nitrogen intermediates (RNI) by the Griess reagent. Superoxide dismutase activation (SOD, NBT assay) and total antioxidant system (FRAP test) were studied. RESULTS: Only the benzene extract at 0.2 mg/mL reduced the biofilms formation. The slight decrease achieved in darkness (17.06 +/- 2.80% reduction) was increased by light action (39.31 +/- 3.50% reduction), clearly observing a photostimulation. This great reduction was confirmed by confocal microscopy. In darkness, biofilm reduction was mediated by an increase in RNI, whereas under irradiation, the ROS action was most important. Although no SOD activation was observed, a strong stimulation of the total antioxidant system was detected. HPLC analysis established a high content of several anthraquinones in this extract. DISCUSSION AND CONCLUSION: Biofilm reduction by benzene extract was mainly mediated by oxidative stress triggered under light action, confirming a photodynamic sensitization, which could be attributed to its high content of photosensitizing anthraquinones. PMID- 27256702 TI - Syk kinase and Shp2 phosphatase inhibition cooperate to reduce FLT3-ITD-induced STAT5 activation and proliferation of acute myeloid leukemia. PMID- 27256705 TI - Genomewide Association Studies in Pharmacogenomics: Meeting Report of the NIH Pharmacogenomics Research Network-RIKEN (PGRN-RIKEN) Collaboration. AB - Genomewide association studies (GWAS) have resulted in the identification of many heritable genetic factors that underlie risk for human disease or variation in physiologic traits. In contrast, there are fewer GWAS of drug response phenotypes, despite extensive unexplained interindividual variability. To address this urgent need, the NIH Pharmacogenomics Research Network (PGRN) and the Center for Integrative Medical Sciences (IMS) at RIKEN support a collaboration, PGRN RIKEN, with the goal of accelerating GWAS of drug response phenotypes. PMID- 27256706 TI - Clinical Trial of Human Umbilical Cord Blood-Derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies. AB - Mesenchymal stem cells (MSCs) have been proven to be therapeutically effective against atopic dermatitis (AD) in preclinical studies. However, the safety and efficacy of MSCs against AD have not yet been investigated in a clinical study. To establish the safety and efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) in AD, 34 adult patients with moderate-to-severe AD were enrolled in two phase trials with a follow-up for 1 month and 3 months, respectively. Patients were randomly allocated to receive low dose (2.5 * 107 ) or high dose (5.0 * 107 ) of hUCB-MSCs subcutaneously. An Eczema Area and Severity Index (EASI) score, Investigator's Global Assessment (IGA) score, Severity Scoring for Atopic Dermatitis (SCORAD) score, adverse effect assessments, and serum biomarker levels were evaluated as end points. A single treatment of hUCB-MSCs resulted in dose-dependent improvements in AD manifestation. Fifty-five percent of patients in high dose hUCB-MSC-treated group showed a 50% reduction in the EASI score. The IGA score and SCORAD score decreased by 33% and 50%, respectively, in high dose treated group. Particularly, the administration of high dose hUCB-MSCs reduced the pruritus score by 58%. The serum IgE levels and number of blood eosinophils were downregulated by the treatment. No serious adverse events occurred, and none of the patients discontinued the trial due to adverse events. This is the first report to demonstrate a marked improvement of AD features with cell therapeutics. These data suggest that the infusion of hUCB-MSCs might be an effective therapy for patients with moderate-to-severe AD. Stem Cells 2017;35:248-255. PMID- 27256707 TI - Discovery of a rhamnose utilization pathway and rhamnose-inducible promoters in Pichia pastoris. AB - The rhamnose utilization pathway in Pichia pastoris has not been clarified although this strain can grow well on rhamnose as a sole carbon source. In this study, four genes, PAS_chr4_0338, PAS_chr4_0339, PAS_chr4_0340, and PAS_chr4_0341, were, for the first time, predicted to be involved in rhamnose metabolism along with the previously identified gene PAS_chr1_4-0075. Moreover, expression of these genes, especially PAS_chr4_0341 and PAS_chr1_4-0075 designated as LRA4 and LRA3, was confirmed to significantly increase and clearly decrease in the presences of rhamnose and glucose, respectively. LRA4 encoding a putative L-2-keto-3-deoxyrhamnonate aldolase, was further confirmed via gene disruption and gene complementation to participate in rhamnose metabolism. Using beta-galactosidase and green fluorescent protein as reporters, the promoters of LRA4 and LRA3 performed well in driving efficient production of heterologous proteins. By using food grade rhamnose instead of the toxic compound methanol as the inducer, the two promoters would be excellent candidates for driving the production of food-grade and therapeutically important recombinant proteins. PMID- 27256708 TI - Height-Adjustable Desks: Energy Expenditure, Liking, and Preference of Sitting and Standing. AB - BACKGROUND: Breaking periods of sitting with standing may prevent chronic diseases and increase energy expenditure (EE). Sit-to-stand height adjustable desks may promote workplace standing, but workers have to be willing to stand for portions of the workday. METHODS: For studies 1 and 2, EE was measured during word processing while sitting in a chair and while standing. Subjects scored their liking of each posture and time they would be willing to work in each posture during an 8-hour workday. Study 2 included an intervention of replacing subjects' sitting desks with a height adjustable desk. Liking of and willingness to work in each posture were measured before and after the 12-month intervention. RESULTS: EE was 7.5 kcal/h greater when standing than when sitting. Subjects liked sitting more than standing in study 1. In study 2, liking of postures did not differ or change across 12 months use of height adjustable desks. Perceived willingness to stand decreased from 4.5 h/d at baseline to 3.4 h/d after 12 months. CONCLUSIONS: Standing rather than sitting increased EE by 7.5 kcal/h. Use of a height adjustable desk for 12 months did not alter the hedonic value of standing or sitting, which is promising for long-term increases in standing. PMID- 27256709 TI - Epicardial fat thickness, an emerging cardiometabolic risk factor, is increased in young adults born preterm. AB - Preterm birth and epicardial fat thickness (EFT) constitute novel risk factors for the onset of future adverse cardiovascular events. In total, 30 ex-extremely low birth weight (ex-ELBW) subjects (10 males, 20 females, aged 17-28) were enrolled and compared with 30 healthy peers. EFT was significantly higher (8.7+/ 0.7 mm v. 5.6+/-0.9 mm; P<0.001) in ex-ELBW than in controls and was correlated with birth weight (r=-0.47, P=0.0009), gestational age (r=-0.39, P=0.03) and cardiac left ventricular mass (r=0.51, P=0.004). When excluding the influence of body mass index, birth weight was the sole remaining determinant of EFT, irrespective of gestational age (r=-0.37, P=0.04). The same findings when excluding the possible influence of blood pressure values on the cardiac structures (r=-0.40, P=0.028). In conclusion, EFT is significantly higher in former preterm subjects and is likewise associated with an increase in left ventricular mass. In view of the acknowledged correlation between the latter and an increased incidence of cardiovascular diseases, EFT appears to be an easy-to measure tool capable of predicting the likely development of future adverse cardiovascular events in these subjects. PMID- 27256710 TI - Systemic lupus erythematosus: SHP2 inhibition ameliorates disease in lupus-prone mice. PMID- 27256712 TI - Experimental arthritis: A protective role for IL-3 in mouse OA. PMID- 27256711 TI - CD8(+) T cells in human autoimmune arthritis: the unusual suspects. AB - CD8(+) T cells are key players in the body's defence against viral infections and cancer. To date, data on the role of CD8(+) T cells in autoimmune diseases have been scarce, especially when compared with the wealth of research on CD4(+) T cells. However, growing evidence suggests that CD8(+) T-cell homeostasis is impaired in human autoimmune diseases. The contribution of CD8(+) T cells to autoimmune arthritis is indicated by the close association of MHC class I polymorphisms with disease risk, as well as the correlation between CD8(+) T-cell phenotype and disease outcome. The heterogeneous phenotype, resistance to regulation and impaired regulatory function of CD8(+) T cells - especially at the target organ - might contribute to the persistence of autoimmune inflammation. Moreover, newly identified populations of tissue-resident CD8(+) T cells and their interaction with antigen-presenting cells might have a key role in disease pathology. In this Review, we assess the link between CD8(+) T cells, autoimmune arthritis and the basis of their homeostatic changes under inflammatory conditions. Improved insight into CD8(+) T cell-specific pathogenicity will be essential for a better understanding of autoimmune arthritis and the identification of new therapeutic targets. PMID- 27256714 TI - Patients with high-risk differentiated thyroid cancer have a lower I-131 ablation success rate than low-risk ones in spite of a high ablation activity. AB - OBJECTIVE: To examine success rates in strictly defined high-risk differentiated thyroid cancer (DTC) patients who received a high-activity (>=5550 MBq) adjuvant postoperative I-131 therapy and compare these to the rates found in highest risk and low-risk patients. DESIGN: Retrospective database study. PATIENTS: We examined 377 patients with DTC who received I-131 ablation. Patients with distant metastases were classified as very high risk. Patients with primary tumours >4 cm, extensive extrathyroidal invasion (pT4a or pT4b in accordance with the 7th edition of the TNM system), and patients with >=5 lymph node metastases or any lateral compartment lymph node metastases were considered high risk. All other patients were considered low risk. MEASUREMENTS: Ablation success rate at first TSH-stimulated follow-up. RESULTS: The ablation success rate was 72.6% in low risk patients, 51.7% in high-risk patients and 13.8% in highest risk patients (all differences P < 0.001). In none of the groups, a significant difference in the initial I-131 activity was found between patients with successful and unsuccessful ablation (low risk: P = 0.16, high risk: P = 0.91 and highest risk: P = 0.48). Furthermore, there was no difference in ablation success between patients who received <5550 MBq and those who received >=5550 Mbq (low risk: P = 0.31, high risk: P = 0.69 and highest risk: P = 0.22). CONCLUSIONS: Patients with high-risk DTC have a significantly reduced I-131 ablation success rate compared to low-risk ones in spite of high initial I-131 activities. As successful ablation is prognostically important, efforts should be made to improve outcome in these patients. PMID- 27256713 TI - The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions. AB - The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host-microorganism interaction is likely to go well beyond taxonomic, correlative observations. In fact, most advances in the field relate to the functional and metabolic capabilities of these microorganisms and their influence on mucosal immunity and systemic inflammation. An intricate relationship between the microbiome and the diet of the host is now fully recognized, with the microbiota having an important role in the degradation of polysaccharides into active metabolites. This Review summarizes the current knowledge on the metabolic role of the microbiota in health and rheumatic disease, including the advances in pharmacomicrobiomics and its potential use in diagnostics, therapeutics and personalized medicine. PMID- 27256715 TI - Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease driven degradation as markers of gout and frequent gout attacks. AB - OBJECTIVE: Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares. METHODS: Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples from 447 men with gout collected at baseline from an ongoing clinical trial, were analysed by ELISA for neo-epitopes from MMP degradation of collagens type I (C1M) and type III (C3M). The log10 levels of both markers were compared between cases and controls and between gout patients with three or more gout attacks in the past year and those with two or less attacks. RESULTS: The circulating levels of C1M and C3M correlated with gout status in the case-control study. Levels of both markers were associated with frequent gout flares (?3 attacks in the past year) in both cohorts (odds ratio, OR = 3.1; 95% CI: 1.4, 6.8; P = 0.0056 for log10C1M, and OR = 6.7; 95% CI: 2.3, 19.3; P = 0.0005 for log10C3M). The area under the curve in a receiver operating characteristic analysis of frequent flares increased from 0.68 to 0.74 in one cohort and from 0.60 to 0.66 in the other when log10C1M and log10C3M were added to clinical variables of the model. CONCLUSION: C1M and C3M, reflective of interstitial matrix destruction, are associated with gout status and with frequent gout flares in men, suggesting that increased MMP activity may contribute to gout flares. Further research is needed to find out whether this is independent of dietary and lifestyle risk factors for acute gout. PMID- 27256717 TI - Dexamethasone intravitreal implant in serpiginous choroiditis. AB - BACKGROUND/AIMS: To assess the efficacy and safety of dexamethasone (DEX) intravitreal implant in patients with active serpiginous choroiditis (SC) already receiving maximal tolerated systemic immunosuppressive therapy. METHODS: In this retrospective longitudinal study we evaluated patients receiving 0.7 mg DEX intravitreal implant for active SC despite maximal systemic immunosuppression. Medical history was reviewed over a period of 18 months for each patient. We diagnosed SC activity using direct fundus examination and blue-light fundus autofluorescence. Primary outcomes were the rate of disease control and functional changes at end of follow-up. Secondary outcomes were the incidence of injection-related adverse events and the success of immunosuppression tapering at the last examination. RESULTS: We examined eight eyes of seven patients. We controlled SC activity with one injection in five eyes, two injections in one eye, and three injections in two eyes (total of 13 implants). Best-corrected visual acuity at the end of the investigational period improved in two eyes (25%), remained stable in four eyes (50%) and decreased in two eyes (25%). Three eyes showed transient intraocular pressure increase and two eyes disclosed cataract progression. The average dosage of systemic prednisone at baseline and after DEX intravitreal implant decreased from 8.8 to 2.8 mg/day. CONCLUSIONS: Dexamethasone intravitreal implant may be an effective treatment option to control active serpiginous lesions in patients in whom increased systemic corticosteroid therapy is contraindicated. PMID- 27256716 TI - Tenascin-C drives persistence of organ fibrosis. AB - The factors responsible for maintaining persistent organ fibrosis in systemic sclerosis (SSc) are not known but emerging evidence implicates toll-like receptors (TLRs) in the pathogenesis of SSc. Here we show the expression, mechanism of action and pathogenic role of endogenous TLR activators in skin from patients with SSc, skin fibroblasts, and in mouse models of organ fibrosis. Levels of tenascin-C are elevated in SSc skin biopsy samples, and serum and SSc fibroblasts, and in fibrotic skin tissues from mice. Exogenous tenascin-C stimulates collagen gene expression and myofibroblast transformation via TLR4 signalling. Mice lacking tenascin-C show attenuation of skin and lung fibrosis, and accelerated fibrosis resolution. These results identify tenascin-C as an endogenous danger signal that is upregulated in SSc and drives TLR4-dependent fibroblast activation, and by its persistence impedes fibrosis resolution. Disrupting this fibrosis amplification loop might be a viable strategy for the treatment of SSc. PMID- 27256718 TI - Tumour lysis syndrome: an unexpected adverse event associated with ipilimumab. PMID- 27256719 TI - Biomechanical differences between left- and right-handed baseball pitchers. AB - Left-handed baseball pitchers are thought to have a number of theoretical advantages compared to right-handed pitchers; however, there is limited scientific research detailing differences in the pitching mechanics of right- and left-handed pitchers. Therefore, this study sought to understand whether any kinematic and kinetic differences existed between right- and left-handed baseball pitchers. A total of 52 collegiate pitchers were included in this study; 26 left handed pitchers were compared to 26 age-, height-, weight- and ball velocity matched right-handed pitchers. Demographic information, passive shoulder range of motion and kinematic and kinetic data were obtained for each pitcher participating in the study. Results indicated that left-handed pitchers did not have a glenohumeral internal rotation deficit as compared to right-handed pitchers. Kinematic analysis indicated that elbow flexion, horizontal glenohumeral abduction and wrist coronal plane motion were significantly different between the two study cohorts. It was also noted that left-handed pitchers had increased elbow varus moments. The findings of this study suggest that pitching coaches should be aware that there are biomechanical differences between left- and right-handed pitchers. PMID- 27256720 TI - Single-Breath Washout Tests to Assess Small Airway Disease in COPD. AB - BACKGROUND: Current functional assessments do not allow a reliable assessment of small airways, which are a major site of disease in COPD. Single-breath washout (SBW) tests are feasible and reproducible methods for evaluating small airway disease. Their relevance in COPD remains unknown. METHODS: We performed a cross sectional study in 65 patients with moderate to severe COPD. Phase III slope of nitrogen (SIIIN2) and double tracer gas (SIIIDTG) SBW tests were used as a measure of ventilation inhomogeneity. The association of both markers with established physiological and clinical features of COPD was assessed. RESULTS: Ventilation inhomogeneity as measured by SIIIN2 and SIIIDTG was increased in patients with COPD compared with healthy subjects (P < .001 and P < .001, respectively). SIIIN2 was associated with FEV1 predicted, residual volume (RV)/total lung capacity (TLC) and diffusing capacity of the lung for carbon monoxide (Dlco) (all P < .001). Furthermore, SIIIN2 was related to dyspnea, exercise-induced desaturation, and exercise capacity (P = .001, P < .001, and P = .047, respectively). SIIIDTG was associated with TLC, Dlco, and cough (P < .001, P = .001, and P = .009, respectively). In multivariate regression models, we demonstrated that these associations are largely independent of FEV1 and mostly stronger than associations with FEV1. In contrast, FEV1 was superior in predicting emphysema severity. CONCLUSIONS: SIIIN2 and SIIIDTG, two fast and clinically applicable measures of small airway disease, reflect different physiological and clinical aspects of COPD, largely independent of spirometry. TRIAL REGISTRY: ISRCTN99586989, Ethics committee Beider Basel (approval number 295/07). PMID- 27256721 TI - Effect of ionic strength on the interfacial viscoelasticity and stability of silk fibroin at the oil/water interface. AB - BACKGROUND: The amphiphilic character and surface activity endows silk fibroin with the ability to reside at fluid interfaces and effectively stabilize emulsions. However, the influence of relevant factors and their actual effect on the interfacial viscoelasticity and stability of silk fibroin at the oil/water interface has received less attention. In the present study, the effect of ionic strength on the interfacial viscoelasticity, emulsification effectiveness and stability of silk fibroin at the oil/water interface was investigated in detail. RESULTS: A higher ion concentration facilitates greater adsorption, stronger molecular interaction and faster structure reorganization of silk fibroin at the oil/water interface, thus causing quicker interfacial saturation adsorption, greater interfacial strength and lower interfacial structural fracture on large deformation. However, the presence of concentrated ions screens the charges in silk fibroin molecules and the zeta potential decreases as a result of electrostatic screening and ion-binding effects, which may result in emulsion droplet coalescence and a decrease in emulsion stability. CONCLUSION: The positively-charged ions significantly affect the interfacial elasticity and stability of silk fibroin layers at the oil/water interface as a result of the strong electrostatic interactions between counter-ions and the negatively-charged groups of silk fibroin. (c) 2016 Society of Chemical Industry. PMID- 27256722 TI - Comparison of dental hygienists and dentists: clinical and teledentistry identification of dental caries in children. AB - RATIONALE FOR STUDY: Teledentistry is an effective and efficient means of increasing access to care for screening, referral and treatment. Practice restrictions and the undocumented concern that dental hygienists do not have the skill or knowledge to identify or diagnose a carious lesion impede access to care. PURPOSE: This study compared the identification of dental caries by both dental hygienists and dentists and by both clinical and teledentistry methods. METHODS: A sample of 82 children 4-7 years of age attending an elementary school in Memphis, Tennessee, was selected for the study. Two clinical examiners, a dental hygienist and dentist, independently examined and charted dental caries and existing restorations separately on the children. Two teledentistry examiners, a dental hygienist and dentist, independently reviewed and charted dental caries and restorations from photographs obtained with the iPhone 4S. Dental charts for each child were converted to a decayed filled surface (DFS) score resulting in four scores for analyses. RESULTS: Seventy-eight children met the inclusion criteria. The clinical dentist's and clinical dental hygienist's DFS scores resulted in Spearman's correlation of r = 0.99. Friedman's analysis of the four examiners' DFS scores found no significant difference (P > 0.10) between the teledentistry dental hygienist's and the clinical dentist's scores. CONCLUSIONS: A dental hygienist can identify dental caries in children 4-7 years of age from photographs as accurately as a dentist in the clinical setting. PMID- 27256723 TI - Chang's meaning of capacitation: A molecular perspective. AB - Dr. Min Chue Chang's contributions to the field of reproductive biology set the stage for the development of the contraceptive pill and in vitro fertilization. Throughout his publications, Dr. Chang was also able to transmit his view of the fertilization process in ways that organized research for newer generations of reproductive biologists. Particularly relevant for the achievement of in vitro fertilization in mammals was the discovery that the sperm required a period of residence in the female tract to become fertilization-competent; Dr. Chang and Dr. Austin, in Australia, independently reported this process, now known as sperm capacitation. This review discusses Dr. Chang's views on capacitation, and puts them in the context of recent advances in the understanding of the molecular basis of this process. Mol. Reprod. Dev. 83: 860-874, 2016 (c) 2016 Wiley Periodicals, Inc. PMID- 27256724 TI - [Immunization strategy of hepatitis B vaccine among adults in China: evidence based-medicine and consideration]. AB - With the effective control of hepatitis B infection among children, the adults especial the young ones become the main population for new hepatitis B virus infection. Now the adults receive hepatitis B vaccination voluntarily and at their own expense in China and the coverage is low. The high immunogenicity of hepatitis B vaccine has been proven among healthy adults. Although the safety of hepatitis B vaccination has been documented among high-risk population such as HIV-infected people, injecting drug users and patients with chronic hepatitis disease, their antibody seroconversion rate after hepatitis B vaccination is lower than the healthy adults. Hepatitis B vaccination is recommended to population at high risk officially in many countries and some effects have been achieved. It is urgent to improve the strategy of hepatitis B vaccination among adults to fasten the control of hepatitis B in China, along with the researches about the long-term efficacy of hepatitis B vaccine among adults, the immunogenicity of hepatitis B vaccination among high-risk adults and the economical evaluation about different adult immunization strategy of hepatitis B. PMID- 27256726 TI - [Antibody persistence following primary vaccination with hepatitis B vaccine among normal and high-responder adults: a 5-year follow-up study]. AB - OBJECTIVE: To evaluate the 5-year antibody persistence and the risk factors associated with the persistence after primary vaccination of hepatitis B vaccine (HepB) among normal or high-response adults. METHODS: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages in north of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 MUg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 MUg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 MUg HepB-SC and 10 MUg HepB derived in Hansenula polymorpha (HepB-HP). The normal and high-responder was followed up and their demographic characteristic (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases were investigated. Blood samples were collected one month (T1) and five years (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. A total of 1 902 participants were followed up and the risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. RESULTS: Among 1 902 adults, 824 (43.32%) were male and 1 078 (56.68%) were female. The anti-HBs positive rate was 100% at T1 and it decreased to 73.29% (1 394 cases) at T2. The corresponding GMC was decreased from 1 527.15 (95%CI: 1 437.84-1 622.01) mU/ml at T1 to 35.07 (95%CI: 32.20-38.19) mU/ml at T2. When comparing with those vaccinated 20 MUg HepB-SC, the significantly lower positive rate at T2 was observed in those vaccinated 10 MUg HepB-SC group and 10 MUg HepB-HP group. The OR (95% CI) was 0.41 (0.28-0.61) and 0.27 (0.18-0.39), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 10 MUg HepB-SC and 10 MUg HepB-HP. The b (95%CI) was -0.20 (-0.28- 0.12) and -0.36 (-0.44- -0.29) , respectively. When comparing with those occasionally drinking, the significantly lower positive rate at T2 was observed in those regular drinking. The OR(95%CI) was 0.51(0.30-0.87). The GMC of anti-HBs in age group of 18-29 was significantly higher than those in 40-49 age group; the b (95%CI) was -0.10(-0.18- -0.01). When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs at T2 was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-2 999 mU/ml and those whose anti-HBs titer was >=10 000 mU/ml. The OR (95%CI) was 10.11 (6.90-14.82), 20.42 (13.98-29.82) and 54.58 (22.08-134.92), respectively. When comparing with those whose anti-HBs titer was <=999 mU/ml at T1, the GMC of anti-HBs at T2 was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was >=10 000 mU/ml. The b (95%CI) was 0.55 (0.47-0.62), 0.94 (0.88-1.00) and 1.63 (1.54-1.72), respectively. Nobody was found positive to HBsAg at T2 and the conversion rate of anti-HBc was 3.89% (74/1 902) at T2. CONCLUSION: Anti-HBs GMC decreased rapidly at T2 among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The antibody persistence among normal and high-responder adults at T2 was associated with HepB type, age, history of drinking and GMC of anti-HBs at T1. PMID- 27256725 TI - [Anti-HBs persistence following primary vaccination with three doses of hepatitis B vaccine among normal and high-responder adults: a 3-year follow-up study]. AB - OBJECTIVE: To assess the 3-year anti-HBs persistence after primary vaccination with three-dose of hepatitis B vaccine (HepB) among normal and high-responder adults. METHODS: A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in local areas for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 MUg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 MUg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 MUg HepB-SC and 10 MUg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). During the follow-up to normal and high-responders, the following information was collected: the demographic characteristic (including age and gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and three years after primary vaccination (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. RESULTS: A total of 4 677 normal and high-responders were identified. Among 4 677 participants, 2 014 (43.06%) were males and 2 663 (56.94%) were females. The positive rate was 100% at T1 and it decreased to 80.99% (3 788/4 677) three years after vaccination. The corresponding GMC was decreased from 1 413.48 (95%CI: 1 358.86-1 470.30) mU/ml to 60.33 (95%CI: 56.97-63.90) mU/ml. When comparing with those vaccinated 20 MUg HepB-CHO, the significantly lower positive rate of anti-HBs three years after vaccination was observed in those vaccinated 20 MUg HepB-SC, 10 MUg HepB-SC and 10 MUg HepB-HP. The OR (95%CI) was 0.65 (0.50-0.84), 0.52 (0.41-0.67) and 0.31 (0.28-0.45), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 20 MUg HepB-SC, 10 MUg HepB-SC and 10 MUg HepB-HP. The b (95%CI) was -0.33 (-0.47- -0.20), -0.41 (-0.55- -0.28) and -0.78 (-0.92- -0.65), respectively. The GMC of anti-HBs in those aged 30-39 years old and 40-49 years old were lower than that in 18-29 years. The b (95%CI) was -0.31 (-0.47- -0.15) and -0.24 (-0.39- -0.09), respectively. When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs three years after vaccination was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-9 999 mU/ml and those whose anti-HBs titer was >=10 000 mU/ml. The OR (95%CI) was 4.97 (3.80-6.49), 7.87 (16.19-10.01) and 9.67 (6.47-14.44), respectively. When comparing with those whose anti-HBs titer was <=999 mU/ml at T1, the GMC of anti-HBs three years after vaccination was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was >=10 000 mU/ml. The b (95%CI) was 1.00 (0.87 1.14), 1.85 (1.74-1.97) and 3.28 (3.12-3.44), respectively. Four subjects showed HBsAg seroconversion and anti-HBc conversion rate was 4.68% at T2. CONCLUSIONS: Anti-HBs GMC decreased rapidly three years after primary vaccination among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The anti-HBs persistence after primary vaccination was associated with HepB type, age and GMC of anti-HBs one month after vaccination. PMID- 27256727 TI - [Anti-HBs persistence following revaccination with three doses of hepatitis B vaccine among low-responsive adults after primary vaccination: a 4-year follow-up study]. AB - OBJECTIVE: To assess the 4-year anti-HBs persistence after revaccination with 3 dose of hepatitis B vaccine (HepB) among low-responsive adults. METHODS: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 MUg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 MUg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 MUg HepB-SC and 10 MUg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The 892 low-responders were revaccinated with three doses of HepB at 0-1-6 months schedule and the type of HepB was the same as which was used for primary immunization. During the follow up to low-responders, the following informations were collected: the demographic characteristics (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and four years after revaccination and anti-HBs, anti-HBc and HBsAg (if anti-HBs <10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively. Anti-HBs titer at T1 was grouped according to the level and was considered as the independent variable in the model analysis. RESULTS: A total of 529 participants were identified from 892 low responders. Among 529 participants, 276 (52.2%) were males and 253 (47.8%) were females. The positive rate was 82.6% (437/529) at T1 and it decreased to 28.2% (149/529) four years after revaccination. The corresponding GMC decreased from 542.06 (95% CI: 466.72-629.56) mU/ml to 27.69 (95% CI: 23.08-33.23) mU/ml. Multivariable analysis showed the positive rate of anti-HBs 4 years after revaccination was independently associated with anti-HBs titer at T1. The positive rate among those whose anti-HBs titer more than 1 000 mU/ml at T1 was significantly higher than those whose anti-HBs titer less than 100 mU/ml. The OR (95%CI) was 39.67 (13.81-114.01). The GMC was associated with HepB type for revaccination and anti-HBs titer at T1. The GMC among those revaccinated 20 MUg HepB was significantly higher than those revaccinated 20 MUg HepB-CHO, 10 MUg HepB-SC and 10 MUg HepB-HP. The b (95% CI) was -0.40 (-0.78--0.02), -0.57 (-1.01- -0.15) and -0.63 (-1.03- -0.23), respectively. The GMC among those whose anti-HBs titer 100-999 mU/ml and those whose anti-HBs titer >=1 000 mU/ml at T1 were higher than those whose anti-HBs titer <100 mU/ml. The b (95% CI) was 0.93 (0.53 1.33) and 3.31 (2.88-3.73) respectively. CONCLUSION: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responsive adults, but still kept good protecion. The anti-HBs persistence after revaccination was associated with HepB type for revaccination and anti-HBs level of titer one month after revaccination. PMID- 27256728 TI - [Anti-HBs persistence after revaccination with three doses of hepatitis B vaccine among non-responsive adults: a 4-year of follow-up study]. AB - OBJECTIVE: To explore anti-HBs persistence four years after revaccination with hepatitis B vaccine (HepB) among adults who were non-responsive to HepB primary immunization. METHODS: A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and aged 18-49 years were selected from 79 villages of Zhangqiu County, Shandong Province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1 6months schedule: 20 MUg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 MUg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 MUg HepB-SC and 10 MUg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were followed up and their basic information and the histories of hepatitis B infection, HepB vaccination, smoking and drinking were investigated. Then they were revaccinated with three doses of HepB with the same schedule as the primary immunization. Blood samples were collected from all of them one month (T1), two years and four years after revaccination and anti-HBs, anti-HBc and HBsAg were detected by CMIA. A total of 356 participants were followed up from 645 low responders four years after revaccination, and the ratio was 55.2%. The risk factors associated with the positive rate and geometric mean concentration (GMC) of anti-HBs after four years of revaccination were analyzed using multivariate unconditional logistic regression model and multivariate linear regression model, respectively. RESULTS: Among 356 participants, 172 (48.3%) were males and 184 (51.7%) were females. The anti-HBs positive rate was 90.4% (322 cases) at T1 and was 55.9% (199 cases) four years after revaccination. The GMC of anti-HBs was 240.5 (95% CI: 186.4-310.4)mU/ml at T1 and decreased to 15.0 (95%CI: 12.2-18.5) mU/ml four years after revaccination. The average annual decreasing rate of GMC was 50.63% from one month after revaccination to four years after revaccination. The corresponding rate was 64.89% in the first two years, which was 2.12 times the rate in the latter two years (30.57%). When compared with those whose anti HBs titer was less than 99 mU/ml at T1, the significantly higher anti-HBs four years after revaccination was observed in those whose anti-HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was >=1 000 mU/ml. The OR (95%CI) was 7.14 (3.90-13.05) and 28.40 (13.16-61.30) respectively. When compared with those whose anti-HBs titer was <=99 mU/ml at T1, the GMC of anti-HBs four years after revaccination was also significantly higher among those whose anti HBs titer at T1 was 100-999 mU/ml and those whose anti-HBs titer at T1 was >=1 000 mU/ml. The b (95%CI) was 1.66 (1.26-2.05) and 3.16 (2.72-3.60), respectively. CONCLUSION: The positive rate and GMC of anti-HBs decreased four years after revaccination among non-responsive adults, but still kept anti-HBs above protective level. The immunity durability after revaccination is mainly associated with anti-HBs titer one month after revaccination. PMID- 27256729 TI - [Study on the dietary intake level for indicator polychlorinated biphenyls in China]. AB - OBJECTIVE: To obtain representative data on levels of indicator polychlorinated biphenyls (PCBs) in foods consumed by the general population and to estimate the dietary intake of indicator PCBs in China. METHODS: The food samples were collected during the fifth China Total Diet Study (2009-2013). Based on the geographical location and dietary habits, China was divided into the south area and the north area, and 10 province regions from each area were chosen. In each province region, one urban site and two rural sites were selected to collect food samples. Considering the food consumption level and the PCBs contaminate rule, a total of 160 samples including meat, eggs, fish, milk, cereals, beans, potatoes and vegetables were selected. The concentration of 7 indicator PCBs in food were determined by stable isotope dilution gas chromatography-mass, and combined with food consumption to calculate the dietary intake of indicator PCBs. RESULTS: The concentration of indicator PCBs in 8 categories of food were in the range of 0.8 1 300.1 pg/g. The levels of indicator PCBs were significantly higher in the aquatic products, averaging (307.8+/-302.4) pg/g, followed by eggs at (76.6+/ 92.1) pg/g and meat at (63.0+/-54.9) pg/g. The daily dietary intake of indicator PCBs varied from province to province, ranging from 0.13 ng.kg(-1).d(-1) to 3.58 ng.kg(-1).d(-1), averaging (0.67+/-0.77) ng.kg(-1).d(-1). Fujian had the highest level (3.58 ng.kg(-1).d(-1)) , followed by Shanghai (1.48 ng.kg(-1).d(-1)) and Zhejiang (1.09 ng.kg(-1).d(-1)) . Compared with the minimum risk level (MRL) value (20 ng.kg(-1).d(-1)) proposed by US Agency for Toxic Substances and Disease Registry, the highest dietary intake level was only 17.9% MRL, the average dietary intake level was 3.4%MRL. Aquatic products was still the major contributor to the dietary intake of indicator PCBs in China, 48% of average dietary intake level (0.32 ng.kg(-1).d(-1)/0.67 ng.kg(-1).d(-1)) . CONCLUSION: The dietary intake of indicator PCBs in China was at a low level, and showing a declining trend. PMID- 27256730 TI - [Analysis on risk factors of screen time among Chinese primary and middle school students in 12 provinces]. AB - OBJECTIVE: To investigate the characteristics of screen time and its risk factors in Chinese primary and middle school students. METHODS: During April 2012 and June 2012, according to the geographical distribution, the stratified random cluster sampling method was used to select 4 provinces from eastern, central and western China, respectively. The convenience sampling method was used to select 2 primary and middle schools from urban, 2 primary and middle schools from rural in each province. In each school, all grades were included, and 2 classes were selected in each grade. A total of 51 866 students or parents were selected as study participants, and 43 771 questionnaires were valid. Information on demographics, academic performance, screen time (TV, computer and cellphone) at weekdays and weekends and the prevalence of the high screen time were compared, multivariate logistic regression was used to analyze the association between screen time >2 h/d and potential influential factors. RESULTS: The percentage of students with screen time >2 h/d at weekdays and weekends were 16.2% (7 082/43 771) and 41.5% (18 141/43 771) (chi(2)=6 280.14, P<0.001), respectively. The distribution of P50 (P25-P75) for screen time at weekdays and weekends were 0.9(0.4-1.6) and 1.8(1.0-3.0) (Z=-131.26, P<0.001), respectively. The results of multinomial logistic regression analysis showed that, at weekdays, subjects characterized as primary school students, boys, urban area, living in western area and sufficient vigorous physical activity <=2 d/w had higher risk for screen time >2 h/d than those characterized as elementary school students, girls, rural area, living in eastern area and sufficient vigorous physical activity >3 d/w, odds ratio were 2.01, 1.54, 1.21, 1.09, and 1.07, respectively (P<0.05 for all); subjects characterized as a normal or worse self rating academic performance had higher risk for screen time >2 h/d than those characterized as a good self rating academic performance, odds ratioes were 1.24 and 1.73, respectively (P<0.05 for all); subjects characterized as paternal education level as elementary school, middle school, high school or secondary school had higher risk for screen time >2 h/d than those characterized as paternal education level as college school or high, odds ratioes were 1.41, 1.47 and 1.52, respectively (P<0.05 for all); subjects characterized as maternal education level as elementary school, middle school and high school or secondary school had higher risk for screen time >2 h/d than those characterized as maternal education level as college, odds ratioes were 1.40, 1.52 and 1.47, respectively (P<0.05 for all). At weekends, subjects characterized as primary school students, boys, urban area and sufficient vigorous physical activity <=2 d/w had higher risk for screen time >2 h/d than those characterized as elementary school students, girls, rural area and sufficient vigorous physical activity >3 d/w, odds ratioes were 2.11, 1.51, 1.20 and 1.05, respectively (P<0.05 for all). At weekends, subjects characterized as a normal or worse self rating academic performance had higher risk for screen time >2 h/d than those characterized as a good self rating academic performance, odds ratioes were 1.09 and 1.26, respectively (P<0.05 for all); subjects characterized as paternal education level as elementary school, middle school, high school or secondary school had higher risk for screen time >2 h/d than those characterized as paternal education level as college school or high, odds ratioes were 1.29, 1.30 and 1.19, respectively (P<0.05 for all); subjects characterized as maternal education level as elementary school, middle school had higher risk for screen time >2 h/d than those characterized as maternal education level as college school or high, odds ratioes were 1.19 and 1.16 and, respectively (P<0.05 for all). CONCLUSION: The prevalence of screen time >2 h/d is high; screen time at weekdays is longer than weekends, and there are significant differences among different sexes, urban or rural areas, living areas, self rating academic performance, parents education levels and physical activity groups. PMID- 27256731 TI - [Prenatal lead exposure related to cord blood brain derived neurotrophic factor (BDNF) levels and impaired neonatal neurobehavioral development]. AB - OBJECTIVE: To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants. METHODS: All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48 MUmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48 MUmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score. RESULTS: Lead content in high exposure group was (0.613+/-0.139) MUmol/L, and higher than (0.336+/-0.142) MUmol/L in low exposure group (t=3.21, P<0.001) . NBNA summary score (36.35+/-1.86), active muscle tension score (6.90+/-0.27) and general assessment score (5.93+/-0.32) in high exposure group were lower than those (38.13+/-0.96, 7.79+/-0.35, 6.00+/ 0.00) in low exposure group (t values were 8.21, 10.23, 2.32, respectively, P values were <0.001, <0.001 and 0.037) . BDNF content in high exposure group which was (3.538+/-1.203) ng/ml was higher than low exposure group (2.464+/-0.918) ng/ml (t=7.60, P<0.001). The correlation analysis found that the cord blood BDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score (r was -0.27, -0.29, -0.30, respectively, P values were <0.001, respectively) . CONCLUSION: Prenatal lead exposure results poor neonatal neurobehavioral development and cord blood BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker. PMID- 27256732 TI - [Temperature modifies the acute effect of particulate air pollution on mortality in Jiang'an district of Wuhan]. AB - OBJECTIVE: To analyze the temperature modification effect on acute mortality due to particulate air pollution. METHODS: Daily non-accidental mortality, cardiovascular mortality, and respiratory mortality data were obtained from Jiang'an District Center for Disease Control and Prevention. Daily meteorological data on mean temperature and relative humidity were collected from China Meteorological Data Sharing Service System. The daily concentration of particulate matter was collected from Wuhan Environmental Monitoring center. By using the stratified time-series models, we analyzed effects of particulate air pollution on mortality under different temperature zone from 2002 to 2010, meanwhile comparing the difference of age, gender and educational level, in Wuhan city of China. RESULTS: High temperature (daily average temperature > 33.4 C) obviously enhanced the effect of PM10 on mortality. With 10 MUg/m(3) increase in PM10 concentrations, non-accidental, cardiovascular, and respiratory mortality increased 2.95% (95%CI: 1.68%-4.24%), 3.58% (95%CI: 1.72%-5.49%), and 5.07% (95%CI: 2.03%-9.51%) respectively. However, low temperature (daily average temperature <-0.21 C) enhanced PM10 effect on respiratory mortality with 3.31% (95% CI: 0.07%-6.64%) increase. At high temperature, PM10 had significantly stronger effect on non-accidental mortality of female aged over 65 and people with high educational level groups. With an increase of 10 MUg/m(3), daily non accidental mortality increased 4.27% (95% CI:2.45%-6.12%), 3.38% (95% CI:1.93% 4.86%) and 3.47% (95% CI:1.79%-5.18%), respectively. Whereas people with low educational level were more susceptible to low temperature. A 10 MUg/m(3) increase in PM10 was associated with 2.11% (95% CI: 0.20%-4.04%) for non accidental mortality. CONCLUSIONS: Temperature factor can modify the association between the PM10 level and cause-specific mortality. Moreover, the differences were apparent after considering the age, gender and education groups. PMID- 27256733 TI - [The etiological and molecular typing research of diarrheagenic Escherichia coli in Henan province in 2013]. AB - OBJECTIVE: To analyze the distribution and pulsed field gel electrophoresis (PFGE) patterns of five kinds of diarrheagenic Escherichia coli (DEC) in infected diarrhea population of Henan province in 2013. METHODS: Gathering 1 037 strains of E. coli of 1 037 diarrhea patients from four sentinel hospitals of multi pathogen monitoring system in Henan province in 2013. Stool samples were cultured with Mac agar plates and using KIA/MIU biochemical action as the preliminary method to identify E. coli strains; preparation of DNA template with thermal cracking method and using multiplex PCR to detect five kinds of DEC. According to molecular typing method published by the international PulseNet bacterial infectious disease monitoring network, the PFGE molecular characteristics of DEC strains were analyzed. RESULTS: 125 DEC positive strains were detected in 1 037 strains of E. coli, the total detection rate was 12.05%. 90 strains were enteroaggregative E.coli (EAEC), detection rate was 8.68% (n=90); 24 strains were enteropathogenic E.coli (EPEC), detection rate was 2.31%; 7 strains were enteroinvasive E.coli (EIEC), detection rate was 0.68%; 4 strains were enterotoxigenic E.coli (ETEC), detection rate was 0.39%; enterohemorrhagic E.coli (EHEC) was not detected. 639 cases of diarrhea samples were collected from male patients, 398 cases were from female patients, 94 positive cases were from male patients, the detection rate was 14.71%.The positive number of female cases were 31 cases, the detection rate was 7.79%. 97 positive cases were detected from 782 countryside cases and 28 positive cases were detected from 255 urban area cases, with detection rate 12.40% and 10.98% respectively. In 125 cases of DEC positive samples, children below 5 years old were 83 cases, accounting for 66.4%; 53 strains of EAEC were divided into 52 molecular patterns by digestion with XbaI and pulsed field gel electrophoresis, each pattern contained 1-2 strains with similarity ranged from 66.3%-100%; 18 strains of EPEC were divided into 18 molecular patterns, each pattern contains 1 strain with similarity ranged from 72.6%-94.8%; 5 strains of EIEC were divided into 5 molecular patterns, each pattern contains 1 strain with similarity ranged from 71.9%-98.5%. 2 strains of ETEC were divided into 2 molecular patterns and similarity below 70%. CONCLUSION: Through the research we could find that four kinds of DEC as a pathogenic bacteria took an important component in pathogenic spectrum of bacterial diarrhea of Henan province in 2013. Four kinds of DEC carrying different virulence genes and taking multiple PFGE patterns showed diversity and complexity characteristics. PMID- 27256734 TI - [Tracing hepatitis C virus transmission by using high-throughput sequencing technique]. AB - OBJECTIVE: An approach for analysis of hepatitis C virus (HCV) quasispecies using Hiseq high-throughput sequencing (hereinafter referred to as Hiseq sequencing) technique was developed and then applied to investigate a possible case of HCV needle sharing transmission. METHODS: One case of HCV antibody seroconversion (P1) was found in a methadone clinic on January 15, 2015. Four HCV antibody positive injecting drug users (IDUs), P2 to P5, suspected to be involved in needle sharing transmission with P1 during the period (after March 24, 2014) that P1 may be infected with HCV were investigated, and another 28 HCV antibody positive IDUs were selected as controls (C1 to C28). These controls came from the same methadone clinic or lived in the same town with P1. The RNAs were extracted from the plasma specimens and then reverse-transcribed into cDNA. After HCV subtyping, Hiseq sequencing was performed to detect and sequence the HCV quasispecies (263 bp) in the specimens with the same subtype as P1. The frequency of quasispecies was counted and ranked. Intrapersonal and interpersonal genetic distance and phylogenetic tree were calculated. RESULTS: The HCV subtype of specimen P1 was 3b. All the other specimens with the same subtype were P2, C7, C12, C14, C15, C16, C19, C20 and C28. Hiseq sequencing was successfully performed in 9 out of these 10 specimens, and 249 753 to 1 086 333 (average 869 608) cleaned sequences representing 3 to 172 (average 48) unique HCV quasispecies were obtained. The medians (P50) of intrapersonal genetic diversities from the 9 specimens were 0.4% to 12.3%. The P50 (P25, P75) of genetic diversities between P1 and the other 8 specimens were 19.0% (18.4%, 19.8%), 10.4% (2.8%, 18.3%), 19.6% (17.8%, 21.4%),24.9% (23.8%, 26.1%), 19.8% (18.7%, 20.7%), 20.1% (18.9%, 21.2%), 20.6% (20.0%, 21.1%), 23.6% (22.4%, 24.8%). There were no significant difference between the genetic diversities of P1 and P2 and those of P1 and other 7 specimens (H=9.40, P=0.100). The genetic diversities between few HCV quasispecies from P1 and few ones from C7 were 0. Phylogenetic tree analysis indicated that there was no HCV transmission relationship between P1 and P2, but there was HCV transmission relationship between P1 and C7. CONCLUSION: With the feature of high-throughput, easier operation and lower cost, Hiseq sequencing technique has high practical value in tracing HCV transmission at the quasispecies level. PMID- 27256735 TI - [Effects of leucine on adipogenesis in 3T3-L1 preadipocytes during and after differentiation]. AB - OBJECTIVE: To observe the effects of leucine on adipogenesis in 3T3-L1 preadipocyte during and after differentiation, and to investigate possible mechanisms. METHODS: Respectively, 0.0 (control), 0.5, 1.0 and 2.0 mmol/L leucine was added in 3T3-L1 cells and cell proliferation was measured by MTT. Then, 3T3 L1 preadipocyte was induced to differentiate. Leucine was added during whole differentiation period, or after differentiation for 4 days. The cells were stained with Oil Red O dye to observe lipid droplet. The culture media were collected and used to determine glycerol contents. Meanwhile, protein expressions related to lypolytic enzymes, leptin signaling pathway were determined by Western blot. RESULTS: MTT result showed that cell viabilities were (100.00+/-12.10)%, (102.73+/-12.38)%, (103.94+/-14.65)%, (108.70+/-5.05)% in 0.0, 0.5, 1.0 and 2.0 mmol/L leucine groups, respectively, there were no significant differences in cell proliferation among 4 groups (F=1.07, P=0.383). When 0.0, 0.5, 1.0 and 2.0 mmol/L leucine was added during differentiation, the relative number of lipid droplet was 1.00+/-0.06, 0.94+/-0.09, 0.82+/-0.08 and 0.79+/-0.04, respectively (F=11.74, P<0.001), and it was significantly lower in 1.0 and 2.0 mmol/L leucine groups than in control group (P=0.002 and P<0.001, respectively). There was no significant difference in lipid droplet when leucine was added after differentiation (F=0.16, P=0.924). When leucine was added during differentiation, the increment of glyceride contents in medium was (65.04 +/- 11.75), (71.45 +/- 23.71), (79.37 +/- 17.63) and (110.32 +/- 25.36) MUmol/L, respectively (F=2.92, P=0.100). And it was significantly higher in 2.0 mmol/L leucine group (110.32 +/- 25.36) MUmol/L than in control group (65.04 +/- 11.75) MUmol/L (t=2.73, P=0.026). No significant difference of the increment of glyceride contents among 4 groups was observed when leucine was added after differentiation (F=0.80, P=0.528). Western blot results showed that leucine treatment during differentiation upregulated expression level of hormone-sensitive lipase phosphorylation (after 0.0 and 2.0 mmol/L leucine treatment,the protein levels were 1.00 +/- 0.08 vs. 2.54 +/- 0.27, P<0.001) , and downregulated the protein expression levels of perilipin A, leptin and leptin-related pathway, such as leptin receptor, Janus kinase 2 and suppressor of cytokine signaling-3 (after 0.0 and 2.0 mmol/L leucine was added, the protein levels were (1.00 +/- 0.03) vs. (0.31 +/- 0.07) , (1.00 +/ 0.08) vs. (0.22+/-0.07) , (1.00+/-0.07) vs. (0.21 +/- 0.04) , (1.00 +/- 0.03) vs. (0.35 +/- 0.05) , (1.00 +/- 0.06) vs. (0.34 +/- 0.05) , P<0.001). Leucine treatment after differentiation had no effects on these protein expressions (all P>0.05). CONCLUSION: Leucine inhibits adipogenesis during 3T3-L1 preadipocyte differentiation by the regulation of lypolytic enzymes and leptin signaling pathway; however, leucine has no effect on adipogenesis when differentiation completed. PMID- 27256737 TI - [Assessing the excess mortality related to short-term and long-term exposure to PM2.5 of Beijing in 2013]. PMID- 27256736 TI - [Investigation and analysis of the coverage rate of hepatitis B vaccine in Gansu province after 12 years since integrated into expanded programme on immunization]. PMID- 27256738 TI - [Investigation on the preventive and control strategies against the first imported case of Zika virus infection in China mainland]. PMID- 27256739 TI - [Experience-based introduction on national public environmental health tracking program and its enlightenment]. PMID- 27256740 TI - [Population genomic researches of Escherichia coli]. AB - Population genomics, an interdiscipline of genomics and population genetics, is booming in recent years with the rapid growth number of deciphered genomes and revolutionizes the understanding of bacterial population diversity and evolution dynamics. It also largely improves the prevention and control of infectious disease through providing more accurate genotyping and source-tracing results and more comprehensive characteristics of emerging pathogens. In this review, taking one of the best characterized bacteria, Escherichia coli, as model, we reviewed the phylogenetic relationship across its five major populations (designated A, B1, B2, D and E); and summarized researches on molecular mutation rate, selection signals, and patterns of adaptive evolution. We also described the application of population genomics in responding against large-scale outbreaks of E. coli O157:H7 and E. coli O104:H4. These results indicated that, although being a novel discipline, population genomics has played an important role in deciphering bacterial population structures, exploring evolutionary patterns and combating emerging infectious diseases. PMID- 27256741 TI - [Research progress of health effect of polybrominated diphenyl ethers]. AB - Polybrominated diphenyl ethers (PBDEs) was one of the most common brominated flame retardants, it has been widely used in products such as furnitures, polymer and plastical material, textiles, electronic products and building materials. PBDEs have potential effect such as neurodevelopmental toxicity, reproductive toxicity, thyroid toxicity, immunological toxicity, embryo toxicity, liver toxicity, teratogenicity and potential carcinogenicity. This paper was aimed to review the environmental exposure way, current level, neurotoxicity, neurodevelopmental toxicity and reproductive toxicity of PBDEs. In recent years, PBDEs has been detected in environment, wildlife animal and human body around the world, there were the significant differences of exposure levels of PBDEs. The most abundant congener were tetra-BDE or BDE-47, hexa-BDE or BDE-153, and deca BDE or BDE-209. Prenatal exposure to PBDEs has great impact on the infants' neurodevelopmental function, induces changes in neuropsychological developmental behavior, decreases of congnition, motivation and attention. High levels of PBDEs have positive relationship with Luteinizing hormone levels, testis disfunction and children's cryptorchidism, and have negative relationship with sperm number and testis size. PMID- 27256742 TI - [Polycyclic aromatic hydrocarbons exposure and birth defects]. AB - Birth defects are one of the most common adverse birth outcomes, which create a heavy economic burden to the country, society and family. And they are also one of the biggest problems facing public health today. Polycyclic aromatic hydrocarbons (PAHs) are a group of toxic pollutants existing in the environment widely, resulting from incomplete organic matter combustion, and can be taken into the body through various ways including the digestive tract, respiratory tract and so on. Recent researches suggest that the exposure of PAHs may be associated with various birth defects, while the special mechanism isn't very clear. This paper is a review of the relationship between PAHs and birth defects from the aspects of epidemiological data, experimental evidence on animals, which indicates that exposure of PAHs during pregnancy may be associated with birth defects including congenital heart defects, neural tube defects and cleft lip/plate. Furthermore, we explored the possible mechanism, including oxidative stress, oxidative damage and the changes of signal transduction pathway in order to provide some recommendations and suggestions on the future work. PMID- 27256744 TI - Favorable efficacy of daclatasvir plus asunaprevir in treatment of elderly Japanese patients infected with HCV genotype 1b aged 70 and older. AB - The combination of daclatasvir and asunaprevir is efficacious in the treatment of hepatitis C virus (HCV) infection, but its efficacy and predictors of efficacy in the elderly (>=70 years) remain unclear. In this study, 844 patients with chronic HCV genotype 1b infection, were treated with daclatasvir (60 mg once daily) plus asunaprevir (100 mg twice daily) for 24 weeks. Using the intention-to-treat analysis, the sustained virological response (SVR) rates were 87% and 88% for all 844 patients and 411 elderly (>70 years of age), respectively. In both groups, multivariate analysis identified NS5A-Y93H mutation (<20%), pretreatment (failure of treatment except for triple therapy with simeprevir, or treatment naive), and level of viremia (<6.0 log IU/ml) as independent predictors of SVR. Direct sequencing showed a significantly higher rate of NS3-D168 mutation at baseline in non-responders to triple therapy with simeprevir (44%) than others (2%). Alfa fetoprotein (AFP) level and liver stiffness were significantly lower after end of treatment than at baseline, in both the SVR and non-SVR groups. In conclusion, daclatasvir-asunaprevir combination achieved high SVR in HCV genotype 1b patients, including elderly patients. Viral factors negatively influenced the response to treatment. Treatment improved AFP level and liver stiffness (surrogate markers of hepatocellular carcinoma), regardless of treatment efficacy. J. Med. Virol. 89:91-98, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27256746 TI - Where's the "Label" for Beet Juice: The Value of the Food and Drug Administration. PMID- 27256747 TI - The Lungs in Heart Failure: Not an Innocent Bystander. PMID- 27256745 TI - Heart Failure Clinical Trials in East and Southeast Asia: Understanding the Importance and Defining the Next Steps. AB - Heart failure (HF) is a major and increasing global public health problem. In Asia, aging populations and recent increases in cardiovascular risk factors have contributed to a particularly high burden of HF, with outcomes that are poorer than those in the rest of the world. Representation of Asians in landmark HF trials has been variable. In addition, HF patients from Asia demonstrate clinical differences from patients in other geographic regions. Thus, the generalizability of some clinical trial results to the Asian population remains uncertain. In this article, we review differences in HF phenotype, HF management, and outcomes in patients from East and Southeast Asia. We describe lessons learned in Asia from recent HF registries and clinical trial databases and outline strategies to improve the potential for success in future trials. This review is based on discussions among scientists, clinical trialists, industry representatives, and regulatory representatives at the CardioVascular Clinical Trialist Asia Forum in Singapore on July 4, 2014. PMID- 27256748 TI - "One Size Does Not Fit All": How to Individualize Decongestive Therapy Strategies in Heart Failure. PMID- 27256749 TI - Precipitating Clinical Factors, Heart Failure Characterization, and Outcomes in Patients Hospitalized With Heart Failure With Reduced, Borderline, and Preserved Ejection Fraction. AB - OBJECTIVES: This study assessed the comparative frequency of precipitating clinical factors leading to hospitalization among heart failure (HF) patients with reduced, borderline, and preserved ejection fraction (EF) BACKGROUND: There are few data assessing the comparative frequency of clinical factors leading to HF among hospitalized among patients with reduced, borderline, and preserved EF. METHODS: We analyzed the factors potentially contributing to HF hospitalization among 99,825 HF admissions from 305 hospitals in the Get With The Guidelines-HF (GWTG-HF) database between January 2005 and September 2013 and assessed their association with length of stay and in-hospital mortality. RESULTS: Mean patient age was 72.6 +/- 14.2 years, 49% were female, and mean EF was 39.3 +/- 17.2%. Common factors included pneumonia/respiratory process (28.2%), arrhythmia (21.7%), medication noncompliance (15.8%), worsening renal failure (14.7%), and uncontrolled hypertension (14.5%). In patients with borderline EF (EF 40% to 49%), pneumonia was associated with longer hospital stay, whereas dietary and medication noncompliance were associated with reduced length of stay. In patients with preserved EF (EF >=50% or qualitative assessment of normal or mild dysfunction), pneumonia, weight gain, and worsening renal function were independently associated with longer lengths of stay. Worsening renal function and pneumonia were independently associated with higher in-hospital mortality in all HF groups, and acute pulmonary edema was associated with higher mortality in reduced EF. Dietary noncompliance (14.7%) was associated with reduced mortality for all groups but reached statistical significance in the subgroups of reduced (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.46 to 0.91) and preserved systolic function (OR: 0.52; 95% CI: 0.33 to 0.83). Patients presenting with ischemia had a higher mortality rate (OR: 1.31; 95% CI: 1.02 to 1.69; and 1.72; 95% CI: 1.27 to 2.33, respectively, in the 2 groups). CONCLUSIONS: Potential precipitating factors among patients hospitalized with HF vary by EF group and are independently associated with clinical outcomes. PMID- 27256750 TI - Understanding Heart Failure With Mid-Range Ejection Fraction. PMID- 27256751 TI - Prolonged QRS in Heart Failure With Preserved Ejection Fraction: Risk Marker and Therapeutic Target? PMID- 27256752 TI - Impaired Pulmonary Diffusion in Heart Failure With Preserved Ejection Fraction. AB - OBJECTIVES: The purpose of this study was to compare measures of gas exchange at rest and during exercise in patients with heart failure and preserved ejection fraction (HFpEF) with age- and sex-matched control subjects. BACKGROUND: Patients with HFpEF display elevation in left heart pressures, but it is unclear how this affects pulmonary gas transfer or its determinants at rest and during exercise. METHODS: Patients with HFpEF (n = 20) and control subjects (n = 26) completed a recumbent cycle ergometry exercise test with simultaneous measurement of ventilation and gas exchange. Diffusion of the lungs for carbon monoxide (DLCO) and its subcomponents, pulmonary capillary blood volume (VC) and alveolar capillary membrane conductance (DM), were measured at rest, and matched for low intensity (20 W) and peak exercise. Stroke volume was measured by transthoracic echocardiography to calculate cardiac output. RESULTS: Compared with control subjects, patients with HFpEF displayed impaired diastolic function and reduced exercise capacity. Patients with HFpEF demonstrated a 24% lower DLCO at rest (11.0 +/- 2.3 ml/mm Hg/min vs. 14.4 +/- 3.3 ml/mm Hg/min; p < 0.01) related to reductions in both DM (18.1 +/- 4.9 ml/mm Hg/min vs. 23.1 +/- 9.1 ml/mm Hg/min; p = 0.04), and VC (45.9 +/- 15.2. ml vs. 58.9 +/- 16.2 ml; p = 0.01). DLCO was lower in patients with HFpEF compared with control subjects in all stages of exercise, yet its determinants showed variable responses. With low-level exercise, patients with HFpEF demonstrated greater relative increases in VC, coupled with heightened ventilatory drive and more severe symptoms of dyspnea compared with control subjects. At 20-W exercise, DM was markedly reduced in patients with HFpEF compared with control subjects. From 20 W to peak exercise, there was no further increase in VC in patients with HFpEF, which in tandem with reduced DM, led to a 30% reduction in DLCO at peak exercise (17.3 +/- 4.2 ml/mm Hg/min vs. 24.7 +/- 7.1 ml/mm Hg/min; p < 0.01). CONCLUSIONS: Subjects with HFpEF display altered pulmonary function and gas exchange at rest and especially during exercise, which contributes to exercise intolerance. Novel therapies that improve gas diffusion may be effective to improve exercise tolerance in patients with HFpEF. PMID- 27256753 TI - Impaired Alveolar Capillary Membrane Diffusion: A Recently Recognized Contributor to Exertional Dyspnea in Heart Failure With Preserved Ejection Fraction. PMID- 27256755 TI - Left Ventricular Ejection Fraction: What Is "Normal"? PMID- 27256756 TI - Social Media: Can It Reduce Heart Failure Events? PMID- 27256754 TI - Prognosis of Adults With Borderline Left Ventricular Ejection Fraction. AB - OBJECTIVES: This study sought to examine the association of a borderline left ventricular ejection fraction (LVEF) of 50% to 55% with cardiovascular morbidity and mortality in a community-based cohort. BACKGROUND: Guidelines stipulate a LVEF >55% as normal, but the optimal threshold, if any, remains uncertain. The prognosis of a "borderline" LVEF, 50% to 55%, is unknown. METHODS: This study evaluated Framingham Heart Study participants who underwent echocardiography between 1979 and 2008 (n = 10,270 person-observations, mean age 60 years, 57% women). Using pooled data with up to 12 years of follow-up and multivariable Cox regression, we evaluated the associations of borderline LVEF and continuous LVEF with the risk of developing a composite outcome (heart failure [HF] or death; primary outcome) and incident HF (secondary outcome). RESULTS: During follow-up (median 7.9 years), HF developed in 355 participants, and 1,070 died. Among participants with an LVEF of 50% to 55% (prevalence 3.5%), rates of the composite outcome and HF were 0.24 and 0.13 per 10 years of follow-up, respectively, versus 0.16 and 0.05 in participants having a normal LVEF. In multivariable-adjusted analyses, LVEF of 50% to 55% was associated with increased risk of the composite outcome (hazard ratio [HR]: 1.37; 95% confidence interval [CI]: 1.05 to 1.80) and HF (HR: 2.15; 95% CI: 1.41 to 3.28). There was a linear inverse relationship of continuous LVEF with the composite outcome (HR per 5 LVEF% decrement: 1.12; 95% CI: 1.07 to 1.16) and HF (HR per 5 LVEF% decrement: 1.23; 95% CI: 1.15 to 1.32). CONCLUSIONS: Persons with an LVEF of 50% to 55% in the community have greater risk for morbidity and mortality relative to persons with an LVEF >55%. Additional studies are warranted to elucidate the optimal management of these individuals. PMID- 27256757 TI - Bad Air Revisited. PMID- 27256758 TI - Reply: Bad Air Revisited. PMID- 27256759 TI - Reply: Antibody-Based Protection of von Willebrand Factor Degradation. PMID- 27256760 TI - Antibody-Based Protection of von Willebrand Factor Degradation. PMID- 27256761 TI - Prognosis in Patients With Takotsubo Cardiomyopathy. PMID- 27256762 TI - Establishing SON in 21q22.11 as a cause a new syndromic form of intellectual disability: Possible contribution to Braddock-Carey syndrome phenotype. AB - A recent study of exome analyses in 109 patients with undiagnosed diseases included a 5-year-old girl with intellectual disability and multiple congenital anomalies, who had an apparently de novo frameshift mutation in SON. However, the combination of the truncating mutation in SON and the phenotype has not been reproduced until date, and it remains unclear if this combination represents a distinctive disease entity. Here we report an additional male with intellectual disability, congenital heart disease, distinctive facial features with curly hair and protruding ears, and long slender extremities, and hyperextensible joints. Exome analysis showed that he had the same de novo frameshift mutation in SON in a heterozygous state. Along with the first and original description of the apparently de novo truncating mutation in SON mentioned above, we have established that haploinsufficiency of SON causes a new recognizable syndrome of intellectual disability. SON is located within 21q22.11, a critical region for Braddock-Carey syndrome, which is characterized by congenital thrombocytopenia, intellectual disability, micrognathia, and a distinctive facies. Therefore, we suggest that the intellectual disability observed in Braddock-Carey syndrome could be accounted for by haploinsufficiency of SON. (c) 2016 Wiley Periodicals, Inc. PMID- 27256763 TI - An open-label pilot study of quetiapine plus mirtazapine for heavy drinkers with alcohol use disorder. AB - Animal research suggests that medications that produce a weak dopamine D2 receptor blockade and potentiate noradrenergic activity may decrease alcohol drinking. In an open-label pilot study of subjects with alcohol dependence, we tested whether the combination of quetiapine, a weak dopamine D2 receptor antagonist, whose primary metabolite, desalkylquetiapine, is a norepinephrine reuptake inhibitor, and mirtazapine, a potent alpha2 norepinephrine receptor antagonist, would decrease alcohol drinking and craving. Twenty very heavy drinkers with alcohol dependence entered a trial of 8 weeks of treatment with quetiapine followed by 8 weeks of treatment with a combination of quetiapine plus mirtazapine. Alcohol use was assessed weekly with a Timeline Follow-Back interview and craving with the Penn Alcohol Craving Scale. Among the 11 completers, subjects reported improved outcomes in the quetiapine plus mirtazapine period compared to the quetiapine alone period: fewer very heavy drinking days per week (1.3 [SD = 2.4] vs. 2.1 [SD = 2.8]; t = 2.3, df = 10, p = 0.04); fewer total number of drinks per week (39.7 [SD = 61.6] vs. 53.4 [SD = 65.0]; t = 2.8, df = 10, p = 0.02); and lower craving scores (2.5 [SD = 1.4] vs. 3.2 [SD = 1.2]; t = 2.4, df = 10, p = 0.04). All subjects reported at least one adverse event; 72.7% reported somnolence. In this open-label pilot study, treatment with quetiapine plus mirtazapine was associated with a decrease in alcohol drinking and craving. These findings are consistent with our previous work in animal models of alcohol use disorders and suggest that further study of medications or combinations of medications with this pharmacologic profile is warranted. PMID- 27256765 TI - Electroosmotic flow in single PDMS nanochannels. AB - The electroosmotic flow (EOF) velocity in single PDMS nanochannels with dimensions as small as 20 nm is investigated systematically by the current slope method in this paper. A novel method for the fabrication of single nanochannels on PDMS surfaces is developed. The effects of channel size, ionic concentration of the electrolyte solution and electric field on the EOF velocity in single nanochannels are investigated. The results show that the EOF velocity in smaller nanochannels with overlapped electric double layers (EDL) is proportional to the applied electric field but is smaller than the EOF velocity in microchannels under the same applied electric field. The EOF velocity in relatively large nanochannels without the overlap of EDLs is independent of the channel size and is the same as that in microchannels under the same applied electric field. Furthermore, in smaller nanochannels with overlapped EDLs, the EOF velocity depends on the ionic concentration and also on the channel size. The experimental results reported in this paper are valuable for the future studies of electrokinetic nanofluidics. PMID- 27256764 TI - Distance to testing sites and its association with timing of HIV diagnosis. AB - Early HIV diagnosis enables prompt treatment initiation, thereby contributing to decreased morbidity, mortality, and transmission. We aimed to describe the association between distance from residence to testing sites and HIV disease stage at diagnosis. Using HIV surveillance data, we identified all new HIV diagnoses made at publicly funded testing sites in central North Carolina during 2005-2013. Early-stage HIV was defined as acute HIV (antibody-negative test with a positive HIV RNA) or recent HIV (normalized optical density <0.8 on the BED assay for non-AIDS cases); remaining diagnoses were considered post-early-stage HIV. Street distance between residence at diagnosis and (1) the closest testing site and (2) the diagnosis site was dichotomized at 5 miles. We fit log-binomial models using generalized estimating equations to estimate prevalence ratios (PR) and robust 95% confidence intervals (CI) for post-early-stage diagnoses by distance. Models were adjusted for race/ethnicity and testing period. Most of the 3028 new diagnoses were black (N = 2144; 70.8%), men who have sex with men (N = 1685; 55.7%), and post-early-stage HIV diagnoses (N = 2010; 66.4%). Overall, 1145 (37.8%) cases traveled <5 miles for a diagnosis. Among cases traveling >=5 miles for a diagnosis, 1273 (67.6%) lived <5 miles from a different site. Residing >=5 miles from a testing site was not associated with post-early-stage HIV (adjusted PR, 95% CI: 0.98, 0.92-1.04), but traveling >=5 miles for a diagnosis was associated with higher post-early HIV prevalence (1.07, 1.02-1.13). Most of the elevated prevalence observed in cases traveling >=5 miles for a diagnosis occurred among those living <5 miles from a different site (1.09, 1.03-1.16). Modest increases in post-early-stage HIV diagnosis were apparent among persons living near a site, but choosing to travel longer distances to test. Understanding reasons for increased travel distances could improve accessibility and acceptability of HIV services and increase early diagnosis rates. PMID- 27256766 TI - G-STRATEGY: Optimal Selection of Individuals for Sequencing in Genetic Association Studies. AB - In a large-scale genetic association study, the number of phenotyped individuals available for sequencing may, in some cases, be greater than the study's sequencing budget will allow. In that case, it can be important to prioritize individuals for sequencing in a way that optimizes power for association with the trait. Suppose a cohort of phenotyped individuals is available, with some subset of them possibly already sequenced, and one wants to choose an additional fixed size subset of individuals to sequence in such a way that the power to detect association is maximized. When the phenotyped sample includes related individuals, power for association can be gained by including partial information, such as phenotype data of ungenotyped relatives, in the analysis, and this should be taken into account when assessing whom to sequence. We propose G-STRATEGY, which uses simulated annealing to choose a subset of individuals for sequencing that maximizes the expected power for association. In simulations, G STRATEGY performs extremely well for a range of complex disease models and outperforms other strategies with, in many cases, relative power increases of 20 40% over the next best strategy, while maintaining correct type 1 error. G STRATEGY is computationally feasible even for large datasets and complex pedigrees. We apply G-STRATEGY to data on high-density lipoprotein and low density lipoprotein from the AGES-Reykjavik and REFINE-Reykjavik studies, in which G-STRATEGY is able to closely approximate the power of sequencing the full sample by selecting for sequencing a only small subset of the individuals. PMID- 27256767 TI - Inhibition of bile canalicular network formation in rat sandwich cultured hepatocytes by drugs associated with risk of severe liver injury. AB - Idiosyncratic drug-induced liver injury is a clinical concern with serious consequences. Although many preclinical screening methods have been proposed, it remains difficult to identify compounds associated with this rare but potentially fatal liver condition. Here, we propose a novel assay system to assess the risk of liver injury. Rat primary hepatocytes were cultured in a sandwich configuration, which enables the formation of a typical bile canalicular network. From day 2 to 3, test drugs, mostly selected from a list of cholestatic drugs, were administered, and the length of the network was semi-quantitatively measured by immunofluorescence. Liver injury risk information was collected from drug labels and was compared with in vitro measurements. Of 23 test drugs examined, 15 exhibited potent inhibition of bile canalicular network formation (<60% of control). Effects on cell viability were negligible or minimal as confirmed by lactate dehydrogenase leakage and cellular ATP content assays. For the potent 15 drugs, IC50 values were determined. Finally, maximum daily dose divided by the inhibition constant gave good separation of the highest risk of severe liver toxicity drugs such as troglitazone, benzbromarone, flutamide, and amiodarone from lower risk drugs. In conclusion, inhibitory effect on the bile canalicular network formation observed in in vitro sandwich cultured hepatocytes evaluates a new aspect of drug toxicity, particularly associated with aggravation of liver injury. PMID- 27256768 TI - Preoperative bowel preparation versus no preparation before spinal surgery: A randomised clinical trial. AB - AIMS AND OBJECTIVES: To investigate the effect of preoperative bowel preparation for patients undergoing spinal fusion surgery. BACKGROUND: Bowel preparation before major surgery is performed routinely to reduce the risk of postoperative complications related to gastrointestinal function. METHODS: A randomised clinical trial was performed that included forty-five elective spinal fusion patients allocated to one control group and two treatment groups. The patients received preoperative bowel preparation with enema, suppository or no bowel preparation. The outcome measures were defecation within 72 hours postoperatively, defecation on the fifth postoperative day, postoperative constipation, nausea, pain, well-being and ambulation. RESULTS: There were significant differences in favour of no bowel preparation compared with suppository group for the primary outcome; days to first defecation. There was a tendency for the patients who received no bowel preparation to recover from constipation more quickly than patients in the bowel preparation groups. The majority of patients did not defecate until the fourth postoperative day. CONCLUSIONS: This randomised study found no benefit from bowel preparation before major spine surgery on gastrointestinal function. The use of bowel preparation is not evidence-based and not performing it should be considered before major spine surgery until the effect is known. PMID- 27256769 TI - Association between Temporal Changes in Primary Care Workforce and Patient Outcomes. AB - OBJECTIVE: To examine the association between 10-year temporal changes in the primary care workforce and Medicare beneficiaries' outcomes. DATA SOURCES: 2001 and 2011 American Medical Association Masterfiles and fee-for-service Medicare claims. STUDY DESIGN/METHODS: We calculated two primary care workforce measures within Primary Care Service Areas: the number of primary care physicians per 10,000 population (per capita) and the number of Medicare primary care full-time equivalents (FTEs) per 10,000 Medicare beneficiaries. The three outcomes were mortality, ambulatory care-sensitive condition (ACSC) hospitalizations, and emergency department (ED) visits. We measured the marginal association between changes in primary care workforce and patient outcomes using Poisson regression models. PRINCIPAL FINDINGS: An increase of one primary care physician per 10,000 population was associated with 15.1 fewer deaths per 100,000 and 39.7 fewer ACSC hospitalizations per 100,000 (both p < .05). An increase of one Medicare primary care FTE per 10,000 beneficiaries was associated with 82.8 fewer deaths per 100,000, 160.8 fewer ACSC hospitalizations per 100,000, and 712.3 fewer ED visits per 100,000 (all p < .05). CONCLUSIONS: Medicare beneficiaries' outcomes improved as the number of primary care physicians and their clinical effort increased. PMID- 27256772 TI - Quantum Router for Single Photons Carrying Spin and Orbital Angular Momentum. AB - Quantum router is an essential element in the quantum network. Here, we present a fully quantum router based on interaction free measurement and quantum dots. The signal photonic qubit can be routed to different output ports according to one control electronic qubit. Besides, our scheme is an interferometric method capable of routing single photons carrying either spin angular momentum (SAM) or orbital angular momentum (OAM), or simultaneously carrying SAM and OAM. Then we describe a cascaded multi-level quantum router to construct a one-to-many quantum router. Subsequently we analyze the success probability by using a tunable controlled phase gate. The implementation issues are also discussed to show that this scheme is feasible. PMID- 27256770 TI - MALDI-Imaging Mass Spectrometry: a step forward in the anatomopathological characterization of stenotic aortic valve tissue. AB - Aortic stenosis (AS) is the most common form of valve disease. Once symptoms develop, there is an inexorable deterioration with a poor prognosis; currently there are no therapies capable of modifying disease progression, and aortic valve replacement is the only available treatment. Our goal is to study the progression of calcification by matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) and get new insights at molecular level that could help in the understanding of this disease. In this work, we analyzed consecutive slices from aortic valve tissue by MALDI-IMS, to establish the spatial distribution of proteins and peptides directly from the surface of the histological sections. The analysis showed different structures corresponding to regions observed in conventional histology, including large calcification areas and zones rich in collagen and elastic fibers. Peptide extraction from the tissue, followed by liquid chromatography mass spectrometry analysis, provided the identification of collagen VI alpha-3 and NDRG2 proteins which correlated with the masses obtained by MALDI-IMS and were confirmed by immunohistochemistry. These results highlighted the molecular mechanism implied in AS using MALDI-IMS, a novel technique never used before in this pathology. In addition, we can define specific regions proving a complementary resolution of the molecular histology. PMID- 27256771 TI - Reconfigurable Liquid Whispering Gallery Mode Microlasers. AB - Engineering photonic devices from liquid has been emerging as a fascinating research avenue. Reconfigurably tuning liquid optical micro-devices are highly desirable but remain extremely challenging because of the fluidic nature. In this article we demonstrate an all-liquid tunable whispering gallery mode microlaser floating on a liquid surface fabricated by using inkjet print technique. We show that the cavity resonance of such liquid lasers could be reconfigurably manipulated by surface tension alteration originated from the tiny concentration change of the surfactant in the supporting liquid. As such, remarkable sensing of water-soluble organic compounds with a sensitivity of free spectral range as high as 19.85 THz / (mol . mL(-1)) and the detectivity limit around 5.56 * 10(-3) mol . mL(-1) is achieved. Our work provides not only a novel approach to effectively tuning a laser resonator but also new insight into potential applications in biological, chemical and environmental sensing. PMID- 27256773 TI - In control? IQC consensus and statutory regulation. AB - Purpose - Internal quality control (IQC) represents an essential risk management tool within the total testing pathway (TTP) that contributes to the overall objective of assuring the quality of results produced in medical laboratories. Controlling analytical phase quality alone requires significant expertise and input by scientifically trained staff. This effort has escalated exponentially following the publication of the International Organisation for Standardisation (ISO)15189:2012 requirements for quality and competence in medical laboratories. The reported inconsistency and diversity to IQC approaches in diagnostic laboratories is definitive evidence that international guidance in IQC programme design and implementation is long overdue. The paper aims to discuss these issues. Design/methodology/approach - Herein, the authors define, describe and critically examine the essential elements four stages of an IQC programme and suggest a template to inform both design and ease of implementation. For practical application, the authors have stratified the proposed methodology into four stages: staff education and training; IQC material; IQC targets; and IQC procedure, and provide recommendations that meet ISO15189:2012 requirements. Findings - These recommendations are informed by the published literature together with the collective experience working in clinical biochemistry and diagnostic endocrinology laboratories. The authors note that the laboratory staff's effort on IQC is a continuous process, driven by changes within each IQC stage, in response to risk analysis, maximising economic value or through professional leadership and central to IQC programme implementation and delivery. Practical implications - The authors offer a template that laboratories can use to inform the design and implementation of their IQC programme. Originality/value - The proposed IQC programme is user friendly, flexible and pragmatic with the potential to harmonise practice. The authors have provided a template to potentially harmonise IQC practice nationally. Given the central and critical role that IQC practice plays in ensuring the quality of patient results' importance, the authors contend that the time has come for international consensus and statutory regulation regarding the minimally acceptable criteria for its implementation, monitoring and review. PMID- 27256774 TI - Laboratory services: regaining and maintaining control. AB - Purpose - After implementing an internal quality control (IQC) programme, the purpose of this paper is to maintain the requisite analytical performance for clinical laboratory staff, thereby safeguarding patient test results for their intended medical purpose. Design/methodology/approach - The authors address how quality can be maintained and if lost, how it can be regained. The methodology is based on the experience working in clinical laboratory diagnostics and is in accord with both international accreditation requirements and laboratory best practice guidelines. Findings - Monitoring test performance usually involves both prospective and retrospective IQC data analysis. The authors present a number of different approaches together with software tools currently available and emerging, that permit performance monitoring at the level of the individual analyser, across analysers and laboratories (networks). The authors make recommendations on the appropriate response to IQC rule warnings, failures and metrics that indicate analytical control loss, that either precludes further analysis, or signifies deteriorating performance and eventual unsuitability. The authors provide guidance on systematic troubleshooting, to identify undesirable performance and consider risk assessment preventive measures and continuous quality improvement initiatives; e.g., material acceptance procedures, as tools to help regain and maintain analytical control and minimise potential for patient harm. Practical implications - The authors provide a template for use by laboratory scientific personnel that ensures the optimal monitoring of analytical test performance and response when it changes undesirably. Originality/value - The proposed template has been designed to meet the International Organisation for Standardisation for medical laboratories ISO15189:2012 requirements and therefore includes the use of External Quality Assessment and patient results data, as an adjunct to IQC data. PMID- 27256775 TI - Waiting time at a fast-track diagnostic clinic. AB - Purpose - Guidelines stating maximum waiting times fail to take cancer patients' expectations into account. Therefore, the purpose of this paper is to assess patients' expectations and experiences with their waiting time at a fast-track clinic. Design/methodology/approach - Patients were selected using a purposeful sampling strategy and were interviewed four times: before the visit; one day after; two weeks after the visit; and one week after starting treatment. Interviews were audiotaped and independently coded by two researchers. Findings - All patients (n=9) preferred a short waiting time before the first visit; they feared that their disease would spread and believed that cancer warrants priority treatment. Six patients experienced the waiting time as short, one had no expectations and two felt they waited longer than expected; three patients changed this evaluation during the study. Six patients received treatment - four preferred to wait before treatment and two wanted to start treatment immediately. Reasons to wait included putting one's affairs in order, or needing to adjust to the diagnosis. Practical implications - Cancer patients prefer a short waiting time before the first visit but have different expectations and needs regarding waiting time before treatment. Ideally, their expectations are managed by their treating physician to match waiting time reality. Originality/value - This is the first study to assess cancer patients' waiting time experiences and how these experiences change over time. This study paves the way for establishing a framework to better assess patient satisfaction with oncology care waiting time. An important aspect, is managing patients' expectations. PMID- 27256776 TI - Has Lean improved organizational decision making? AB - Purpose - Sustainable improvement is likely to be hampered by ambiguous objectives and uncertain cause-effect relations in care processes (the organization's decision-making context). Lean management can improve implementation results because it decreases ambiguity and uncertainties. But does it succeed? Many quality improvement (QI) initiatives are appropriate improvement strategies in organizational contexts characterized by low ambiguity and uncertainty. However, most care settings do not fit this context. The purpose of this paper is to investigate whether a Lean-inspired change program changed the organization's decision-making context, making it more amenable for QI initiatives. Design/methodology/approach - In 2014, 12 professionals from a Dutch radiotherapy institute were interviewed regarding their perceptions of a Lean program in their organization and the perceived ambiguous objectives and uncertain cause-effect relations in their clinical processes. A survey (25 questions), addressing the same concepts, was conducted among the interviewees in 2011 and 2014. The structured interviews were analyzed using a deductive approach. Quantitative data were analyzed using appropriate statistics. Findings Interviewees experienced improved shared visions and the number of uncertain cause-effect relations decreased. Overall, more positive (99) than negative Lean effects (18) were expressed. The surveys revealed enhanced process predictability and standardization, and improved shared visions. Practical implications - Lean implementation has shown to lead to greater transparency and increased shared visions. Originality/value - Lean management decreased ambiguous objectives and reduced uncertainties in clinical process cause-effect relations. Therefore, decision making benefitted from Lean increasing QI's sustainability. PMID- 27256777 TI - An improvement model to optimise hospital interdisciplinary learning. AB - Purpose - Interdisciplinary healthcare education and collaboration facilitates healthcare quality improvement (QI). Education challenges include cost, logistics and defining the optimum staff-engaging method. The purpose of this paper is to determine the optimum QI educational model and measure its impact using plan-do study-act (PDSA) cycles. Design/methodology/approach - The authors established an on-site interdisciplinary QI learning collaborative: weekly 30-minute learning sessions close to the working environment; a learning materials Twitter repository; and junior doctor-led QI work streams aligned with surgical directorate quality goals supported by a mentorship network. Delivery style (lectures, workshops and QI project reporting) and learning session content was planned weekly using PDSA cycles and modified using participant feedback (score 0 10). All surgical directorate QI work streams were measured before and at nine months. Findings - From May 2014 to February 2015, there were 32 learning sessions with 266 scores (median 12 weekly, range 5-21). Workshop delivery scored the highest (mean score 9.0), followed by live project reports (mean score 8.8). The surgical QI work streams increased threefold from four to 12, including six junior doctor-led projects. Practical implications - By proactively acting upon feedback, the authors centralised QI measurement and tailored learning sessions to staff needs. Building sustainability involves continually refining learning curriculum and QI work streams, and expanding the mentorship network. Originality/value - The collaborative was established at no additional cost. Twitter is used to promote meetings, facilitate conversations and act as a learning repository. The mentorship framework builds QI and coaching expertise. PMID- 27256778 TI - Healthcare waste management: an interpretive structural modeling approach. AB - Purpose - The World Health Organization identified infectious healthcare waste as a threat to the environment and human health. India's current medical waste management system has limitations, which lead to ineffective and inefficient waste handling practices. Hence, the purpose of this paper is to: first, identify the important barriers that hinder India's healthcare waste management (HCWM) systems; second, classify operational, tactical and strategical issues to discuss the managerial implications at different management levels; and third, define all barriers into four quadrants depending upon their driving and dependence power. Design/methodology/approach - India's HCWM system barriers were identified through the literature, field surveys and brainstorming sessions. Interrelationships among all the barriers were analyzed using interpretive structural modeling (ISM). Fuzzy-Matrice d'Impacts Croises Multiplication Appliquee a un Classement (MICMAC) analysis was used to classify HCWM barriers into four groups. Findings - In total, 25 HCWM system barriers were identified and placed in 12 different ISM model hierarchy levels. Fuzzy-MICMAC analysis placed eight barriers in the second quadrant, five in third and 12 in fourth quadrant to define their relative ISM model importance. Research limitations/implications - The study's main limitation is that all the barriers were identified through a field survey and barnstorming sessions conducted only in Uttarakhand, Northern State, India. The problems in implementing HCWM practices may differ with the region, hence, the current study needs to be replicated in different Indian states to define the waste disposal strategies for hospitals. Practical implications - The model will help hospital managers and Pollution Control Boards, to plan their resources accordingly and make policies, targeting key performance areas. Originality/value - The study is the first attempt to identify India's HCWM system barriers and prioritize them. PMID- 27256779 TI - Comparing and improving chronic illness primary care in Sweden and the USA. AB - Purpose - The purpose of this paper is to identify opportunities for improving primary care services for people with chronic illnesses by comparing how Sweden and US services use evidence-based practices (EBPs), including digital health technologies (DHTs). Design/methodology/approach - A national primary healthcare center (PHCC) heads surveys in 2012-2013 carried out in both countries in 2006. Findings - There are large variations between the two countries. The largest, regarding effective DHT use in primary care centers, were that few Swedish primary healthcare compared to US heads reported having reminders or prompts at the point of care (38 percent Sweden vs 84 percent USA), despite Sweden's established electronic medical records (EMR). Swedish heads also reported 30 percent fewer centers receiving laboratory results (67 percent Sweden vs 97 percent USA). Regarding following other EBPs, 70 percent of Swedish center heads reported their physicians had easy access to diabetic patient lists compared to 14 percent in the USA. Most Swedish PHCC heads (96 percent) said they offered same day appointment compared to 36 percent in equivalent US practices. Practical implications - There are opportunities for improvement based on significant differences in effective practices between the countries, which demonstrates to primary care leaders that their peers elsewhere potentially provide better care for people with chronic illnesses. Some improvements are under primary care center control and can be made quickly. There is evidence that people with chronic illnesses in these two countries are suffering unnecessarily owing to primary care staff failing to provide proven EBP, which would better meet patient needs. Public finance has been invested in DHT, which are not being used to their full potential. Originality/value - The study shows the gaps between current and potential proven effective EBPs for services to patients with chronic conditions. Findings suggest possible explanations for differences and practical improvements by comparing the two countries. Many enhancements are low cost and the proportionate reduction in suffering and costs they bring is high. PMID- 27256780 TI - Archaeological excavation of wild macaque stone tools. PMID- 27256781 TI - Separation of plastics: The importance of kinetics knowledge in the evaluation of froth flotation. AB - Froth flotation is a promising technique to separate polymers of similar density. The present paper shows the need for performing kinetic tests to evaluate and optimize the process. In the experimental study, batch flotation tests were performed on samples of ABS and PS. The floated product was collected at increasing flotation time. Two variables were selected for modification: the concentration of the depressor (tannic acid) and airflow rate. The former is associated with the chemistry of the process and the latter with the transport of particles. It was shown that, like mineral flotation, plastics flotation can be adequately assumed as a first order rate process. The results of the kinetic tests showed that the kinetic parameters change with the operating conditions. When the depressing action is weak and the airflow rate is low, the kinetic is fast. Otherwise, the kinetic is slow and a variable percentage of the plastics never floats. Concomitantly, the time at which the maximum difference in the recovery of the plastics in the floated product is attained changes with the operating conditions. The prediction of flotation results, process evaluation and comparisons should be done considering the process kinetics. PMID- 27256782 TI - Improving biogas quality and methane yield via co-digestion of agricultural and urban biomass wastes. AB - Impact of co-digestion versus mono-digestion on biogas and CH4 yield for a set of five biomass materials (vegetable food waste, cow dung, pig manure, grass clippings, and chicken manure) was investigated considering 95 different biomass mixes of the five materials under thermophilic conditions in bench-scale batch experiments over a period of 65days. Average biogas and CH4 yields were significantly higher during co-digestion than during mono-digestion of the same materials. This improvement was most significant for co-digestion experiments involving three biomass types, although it was independent of the specific biomasses being co-digested. Improvement in CH4 production was further more prominent early in the digestion process during co-digestion compared to mono digestion. Co-digestion also appeared to increase the ultimate CH4/CO2 ratio of the gas produced compared to mono-digestion although this tendency was relatively weak and not statistically significant. PMID- 27256783 TI - A solvent-free approach to extract the lipid fraction from sewer grease for biodiesel production. AB - Fats, oils and greases (FOG) are the number one cause of sewer pipe blockage and have been mostly disposed of as a waste until recently. This study investigated a low cost and environmentally friendly approach to extract the lipid fraction (fatty acids and glycerides for biodiesel production) from sewer grease (SG), i.e., FOGs obtained from wastewater treatment plants (WWTPs). The lipid fraction of the sewer grease was primarily in the form of free fatty acid (FFA), at 20.7wt%. An innovative solvent-free extraction approach was developed using waste cooking oil (WCO) to overcome the challenges of emulsion, impurities and high moisture content of the sewer grease. A 95% extraction yield of sewer grease was achieved under the optimum operating condition of 3.2:1 WCO-SG ratio (wt/wt), 70 degrees C and 240min. In addition, the reusability of the WCO was also investigated. WCO can be used two to three times for sewer grease extraction with more than 90% extraction efficiency. PMID- 27256784 TI - Posterior curve correction using convex posterior hemi-interbody arthrodesis in skeletally immature patients with scoliosis. AB - BACKGROUND CONTEXT: Deformity progression after posterior fusion in skeletally immature patients with scoliosis has remained a topic of debate. It occurs when the anterior segment of the apical zone continues to grow after successful posterior fusion, resulting in progressive bending and rotation of the vertebral bodies. For this reason, circumferential fusion using a combined anterior posterior approach has been used to prevent this occurrence. PURPOSE: The aim of this study was to report instrumented spinal fusion with convex hemi-interbody arthrodesis using a posterior-only approach in Risser stage 0 or 1 scoliosis patients. STUDY DESIGN: This is a retrospective study. PATIENT SAMPLE: Three patients presenting scoliosis in Risser stage 0 or 1 were enrolled. OUTCOME MEASURES: Postoperative correction rate, bone union, and pulmonary function were examined. METHODS: Premenarchal girls aged 11.3-12.2 years underwent surgical procedure. Follow-up after surgery was on 25, 30, and 36 months. The surgical procedure included soft tissue, costotransverse ligament and facet releases, and Ponte osteotomies. Discectomy followed by intervertebral bone grafting were performed across the periapical zone on the convex side. After placement of segmental pedicle screws, deformity correction was achieved by rod derotation, cantilever reduction, direct vertebral derotation distraction and compression technique. RESULTS: Preoperative thoracic Cobb angle measured 81 degrees (range 64-107), which improved to 23 degrees at final follow-up, resulting in a 72% correction. Solid posterior bony fusion was achieved in all cases at final follow up. No case showed deterioration of axial rotation at the apex radiographically. Postoperative pulmonary function showed increases in forced vital capacity (preoperation: 1.86+/-0.2L; at 2 years: 2.48+/-0.1L) and forced expiratory volume in 1 second (preoperation: 1.58+/-0.2L; at 2 years: 2.11+/-0.1L). CONCLUSIONS: This posterior-only procedure should be considered a suitable option in skeletally immature scoliosis patients where circumferential fusion is indicated and avoiding an anterior thoracotomy is preferable. PMID- 27256785 TI - Sacral extradural arachnoid cyst in association with split cord malformation. AB - BACKGROUND CONTEXT: Split cord malformation (SCM) is a congenital disease that can be associated with other spinal anomalies. Few cases of concurrent intradural arachnoid cyst and SCM have been sporadically reported; however, sacral extradural arachnoid cyst (SEAC) with SCM is very rare. PURPOSE: The report describes our experience with simultaneous surgery in patients with concurrent SEAC and SCM in an effort to document the treatment of the rare spinal concomitant anomalies. STUDY DESIGN: The present study is designed as a case series. PATIENT SAMPLE: This is a continuous series of patients with coexisting SCM and SEAC who were presented to our institution. OUTCOME MEASURES: The lower extremities weakness and deformity, radiological imaging, urodynamic tests, and surgical aspects of the patient population are documented. METHODS: Cases with concomitant anomalies were consecutively enrolled among 73 patients who were operated on for SCM between 2008 and 2014. Clinical data and surgical findings were prospectively filed and retrospectively evaluated. RESULTS: There were seven patients (2 boys and 5 girls), with age ranging from 18 to 119 months (mean: 56.71+/-39.49). Type I SCM was detected in six cases, and type II SCM was detected in one case. Tethering of the cord was detected in all seven patients, and six patients (85.7%) had syrinx formation rostral to the level of SCM. All patients had at least one kind of urological dysfunctions manifesting as neurogenic bladder. On surgery, fistulous orifice of the meningeal cyst was found and ligated in six cases, and the other one was repaired via sealing the cyst walls as near as possible to the thecal sac. CONCLUSIONS: In patients with symptomatic SCM, the signs of concurrent SEAC may be masqueraded by the former condition. It would be impossible to attribute a given sign, particularly urological signs, to either SCM or SEAC. Whatever the sign and nature, both conditions are better to be managed surgically in one session under a single anesthesia to prevent duplicate complications of further anesthesia and interventions in scar tissue. PMID- 27256786 TI - Corrigendum to "The development of an estimation model for energy expenditure during water walking by acceleration and walking speed" [J. Sci. Med. Sport 17 (1) (2014) 96-101]. PMID- 27256787 TI - Validation of the SenseWear Mini activity monitor in 5-12-year-old children. AB - OBJECTIVES: This study aimed to validate SenseWear Mini software algorithm versions 2.2 (SW2.2) and 5.2 (SW5.2) for estimating energy expenditure (EE) in children. DESIGN: Laboratory-based validation study. METHODS: 57 children aged 5 12 y completed a protocol involving 15 semi-structured sedentary (SED), light intensity (LPA), and moderate- to vigorous-intensity (MVPA) physical activities. EE was estimated using portable indirect calorimetry (IC). The accuracy of EE estimates (kcal.min-1) from SW2.2 and SW5.2 were examined at the group level and individual level using the mean absolute percentage error (MAPE), Bland-Altman plots and equivalence testing. RESULTS: MAPE values were lower for SW5.2 (30.1+/ 10.7%) than for SW2.2 (44.0+/-6.2%). Although mean differences for SW5.2 were smaller than for SW2.2 during SED (-0.23+/-0.22 vs. -0.61+/-0.20kcal.min-1), LPA (-0.69+/-0.76 vs. -1.07+/-0.46kcal.min-1) and MVPA (-2.22+/-1.15 vs. -2.57+/ 1.15kcal.min-1), limits of agreement did not decrease for the updated algorithms. For all activities, SW2.2 and SW5.2 were not equivalent to IC (p>0.05). Errors increased with increasing intensity. CONCLUSION: The current SenseWear Mini algorithms SW5.2 underestimated EE. The overall improved accuracy for SW5.2 was not accompanied with improved accuracy at the individual level and EE estimates were not equivalent to IC. PMID- 27256788 TI - Postactivation potentiation of dynamic conditioning contractions on rowing sprint performance. AB - OBJECTIVES: This study examined the post-activation potentiation effects of maximal dynamic contractions and gender on rowing sprint ability. DESIGN: Repeated measures. METHODS: Thirty-four male (n=17) and female (n=17) university students with experience in rowing took part in this study conducted across three weeks. Following familiarisation of the 10-second maximal rowing performance test on a rowing ergometer during Week 1, participants were randomly allocated to either complete a control or experimental session during Week 2 and 3. One rowing performance test was conducted during the control session whilst two rowing performance tests were conducted during the experimental session separated by 6 min. The first rowing performance test during the experimental session was used to: (1) compare measures with the control session to assess day-to-day repeatability; and (2) induce post-activation potentiation effects for the second rowing performance test. RESULTS: Based on effect size calculations, results showed moderate-large increases for average power output (+2.5%), peak power output (+1.5%) and power output during first stroke (+0.79%). CONCLUSIONS: Maximal dynamic contractions on a rowing ergometer improved subsequent rowing sprint ability in recreationally experienced male and female rowers. Accordingly, dynamic conditioning contractions on a rowing ergometer may enhance subsequent sprint-start for rowing competition success. PMID- 27256789 TI - Mechanical alterations during interval-training treadmill runs in high-level male team-sport players. AB - OBJECTIVES: To examine mechanical alterations during interval-training treadmill runs in high-level team-sport players. DESIGN: Within-participants repeated measures. METHODS: Twenty high-level male field-hockey players performed six 30-s runs at 5.53+/-0.19ms-1 corresponding to 115% of their velocity associated with maximal oxygen uptake (vVO2max) with 30-s passive recovery on an instrumented treadmill. Continuous measurement of running kinetics/kinematics and spring-mass characteristics were performed and values were subsequently averaged over 20s (8th-28ths) for comparison. RESULTS: Contact time (+1.1+/-4.3%; p=0.044), aerial time (+4.1+/-5.3%; p=0.001), step length (+2.4+/-2.2%; p<0.001) along with mean loading rates (+7.1+/-10.6%; p=0.026) increased from the first to the last interval, whereas step frequency (-2.3+/-2.1%; p<0.001) decreased. Both centre of mass vertical displacement (+3.0+/-6.0%; p<0.001) and leg compression (+2.8+/ 9.7%; p=0.036), but not peak vertical forces (0.0+/-4.1%; p=0.761), increased with fatigue. Vertical stiffness decreased (-2.8+/-6.9%; p=0.012), whereas leg stiffness did not change across intervals (p=0.149). CONCLUSIONS: During interval training treadmill runs, high-level team-sport players modified their mechanical behaviour towards lower vertical stiffness while preserving a constant leg stiffness. Maintenance of running velocity induced longer step lengths and decreased step frequencies that were also accompanied by increased impact loading rates. These mechanical alterations occurred early during the set. PMID- 27256790 TI - Monoterpenes and sesquiterpenes from the marine sediment-derived fungus Eutypella scoparia FS46. AB - Eutypellol A (1), the first norsesquiterpenoid of sequicarene family, as well as eutypellol B (2), a rare 7-methyl oxidized 2-carene derivative, and one new natural product 2-(2-hydroxy-4-methylcyclohex-3-enyl)propanoic acid (3), along with eight known terpenoids, were isolated from the marine sediment-derived fungus Eutypella scoparia FS46 collected from the South China Sea. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 1-3 were evaluated for their antibacterial activities against Staphylococcus aureus and cytotoxic activities against MCF-7, NCI-H460, and SF 268 tumor cell lines. PMID- 27256791 TI - Electrical Oscillations in Two-Dimensional Microtubular Structures. AB - Microtubules (MTs) are unique components of the cytoskeleton formed by hollow cylindrical structures of alphabeta tubulin dimeric units. The structural wall of the MT is interspersed by nanopores formed by the lateral arrangement of its subunits. MTs are also highly charged polar polyelectrolytes, capable of amplifying electrical signals. The actual nature of these electrodynamic capabilities remains largely unknown. Herein we applied the patch clamp technique to two-dimensional MT sheets, to characterize their electrical properties. Voltage-clamped MT sheets generated cation-selective oscillatory electrical currents whose magnitude depended on both the holding potential, and ionic strength and composition. The oscillations progressed through various modes including single and double periodic regimes and more complex behaviours, being prominent a fundamental frequency at 29 Hz. In physiological K(+) (140 mM), oscillations represented in average a 640% change in conductance that was also affected by the prevalent anion. Current injection induced voltage oscillations, thus showing excitability akin with action potentials. The electrical oscillations were entirely blocked by taxol, with pseudo Michaelis-Menten kinetics and a KD of ~1.29 MUM. The findings suggest a functional role of the nanopores in the MT wall on the genesis of electrical oscillations that offer new insights into the nonlinear behaviour of the cytoskeleton. PMID- 27256792 TI - Head growth in fetuses with isolated congenital heart defects: lack of influence of aortic arch flow and ascending aorta oxygen saturation. AB - OBJECTIVES: Congenital heart defects (CHDs) are reported to be associated with a smaller fetal head circumference (HC) and neurodevelopmental delay. Recent studies suggest that altered intrauterine brain hemodynamics may explain these findings. Our objectives were to evaluate the pattern of head growth in a large cohort of fetuses with various types of CHD, analyze these patterns according to the type of CHD and estimate the effect of cerebral hemodynamics with advancing gestation in the second and third trimesters. METHODS: Singleton fetuses with an isolated CHD were selected from three fetal medicine units (n = 436). Cases with placental insufficiency or genetic syndromes were excluded. CHD types were clustered according to the flow and oxygen saturation in the aorta. Z-scores of biometric data were constructed using growth charts of a normal population. HC at different gestational ages was evaluated and univariate and multivariate mixed regression analyses were performed to examine the patterns of prenatal HC growth. RESULTS: Fetuses with severe and less severe types of CHD demonstrated statistically significant HC growth restriction with increasing gestational age (slope of -0.017/day); however, there was no statistically significant effect of fetal hemodynamics on HC growth. Fetuses with CHD but normal brain oxygenation and normal aortic flow showed a significant decrease in HC growth (slope of 0.024/day). Only fetuses with isolated tetralogy of Fallot demonstrated a smaller HC z-score at 20 weeks of gestation (-0.67 (95% CI, -1.16 to -0.18)). CONCLUSIONS: Despite the decline in head growth in fetuses with a prenatally detected isolated CHD, HC values were within the normal range, raising the question of its clinical significance. Furthermore, in contrast to other studies, this large cohort did not establish a significant correlation between aortic flow or oxygen saturation and HC growth. Factors other than altered fetal cerebral hemodynamics may contribute to HC growth restriction with increasing gestational age, such as (epi)genetic or placental factors. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27256793 TI - 8-isoprostanes and resistin as markers of vascular damage in non-hypersomnolent obstructive sleep apnoea patients. AB - BACKGROUND: Oxidative stress and inflammation are assumed as the main pathological triggers for vascular damage in hypersomnolent obstructive sleep apnoea (OSA) patients, whereas their exact role in less symptomatic population is currently unknown. AIM: To determine whether oxidative stress (urinary 8 isoprostane concentration) and inflammation (plasma resistin levels) are associated with vascular damage in non-hypersomnolent (Epworth Sleep Score <11) OSA patients. METHODS: A total of 325 consecutive patients have undergone standard polysomnography, and 256 of them were diagnosed with OSA. Excessive daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Only 86 patients with ESS <11 participated in the study. The control group was presented by 45 subjects without OSA. Endothelial function was assessed by ultrasonographic measurement of flow-mediated dilatation (FMD). Intima-media thickness (IMT) and ankle-brachial index (ABI) were determined by ultrasonography. Urinary 8 isoprostanes (Cayman Chemical, USA) were measured, applying mass spectrometry. Resistin (RayBio_ Human ResistinCat#:ELH-Resistin-001) plasma levels were detected by ELISA. RESULTS: In patients with OSA, flow-mediated dilatation was significantly lower than in control subjects (4.62% +/-1.9) and (7.1% +/-2.8), respectively (P: 0.013). The prevalence of plaques in a.carotis communis was higher in OSA (16% versus 4%). The same is observed regarding a.tibialis posterior (81% vs. 29%). The average IMT and ABI in OSA and in the control group were, respectively, (IMT - 800 um versus. 666 um); (ABI -1.06 versus 1.20). Urinary isoprostanes were higher in OSA patients (0.091 versus 0.078) and correlated negatively to FMD (r: -0.825, P: 0.00), IMT (r: -0.324, P: 0.003) and ABI (r: -0.226, P: 0.043). No association between resistin and the degree of vascular injury was found. CONCLUSIONS: In comparison with the control group, increased prevalence of endothelial dysfunction and vascular damage was established in OSA patients without excessive daytime sleepiness. Urinary 8 isoprostanes (oxidative stress markers) are closely associated with FMD (endothelial dysfunction), IMT and ABI (vascular damage). Resistin plasma levels correlated neither to FMD, nor to IMT or ABI. PMID- 27256794 TI - Eco-evolutionary dynamics of social dilemmas. AB - Social dilemmas are an integral part of social interactions. Cooperative actions, ranging from secreting extra-cellular products in microbial populations to donating blood in humans, are costly to the actor and hence create an incentive to shirk and avoid the costs. Nevertheless, cooperation is ubiquitous in nature. Both costs and benefits often depend non-linearly on the number and types of individuals involved-as captured by idioms such as 'too many cooks spoil the broth' where additional contributions are discounted, or 'two heads are better than one' where cooperators synergistically enhance the group benefit. Interaction group sizes may depend on the size of the population and hence on ecological processes. This results in feedback mechanisms between ecological and evolutionary processes, which jointly affect and determine the evolutionary trajectory. Only recently combined eco-evolutionary processes became experimentally tractable in microbial social dilemmas. Here we analyse the evolutionary dynamics of non-linear social dilemmas in settings where the population fluctuates in size and the environment changes over time. In particular, cooperation is often supported and maintained at high densities through ecological fluctuations. Moreover, we find that the combination of the two processes routinely reveals highly complex dynamics, which suggests common occurrence in nature. PMID- 27256795 TI - Papular purpuric gloves and socks syndrome. PMID- 27256797 TI - Health-related quality of life after treatment for neoplasia of the major salivary glands: a pilot study. AB - Treatment of malignancy of the salivary glands risks damage to the cranial nerves, and clinicians' traditional view has been that this will result in adverse effects on physical function and subsequent health-related quality of life (QoL). Preservation of nerves has been advocated to lessen this impact, but we know of no evidence that sacrifice of the facial nerve has any effect on subsequent QoL. We collected data prospectively before and after operation for all malignancies of the major salivary glands treated over five years using two health-related QoL questionnaires: the University of Washington Quality of Life Questionnaire and the Patient Concerns Inventory. Fifteen of17 eligible patients fulfilled the inclusion criteria by having assessments completed both before and after operation. Scores for QoL after treatment of cancer of the submandibular gland dropped at six months, but had resolved to more than 80% of the pretreatment score by a year, with the exception of the domains taste and saliva. The four patients who had weakness of the facial nerve after treatment had appreciable reductions in the physical function components of the QoL domains, but no significant reduction in the social-emotional domains. Use of the Patient Concerns Inventory enables tailoring of services towards those clinicians who a patient feels are potentially most likely to help alleviate factors that have an adverse effect on QoL. Sacrifice of the facial nerve in malignant parotid gland disease results in a considerable reduction in functional health-related QoL scores. Methods to ensure clearance of the tumour while limiting the effects on facial nerve function should always be considered. PMID- 27256796 TI - Chondrogenesis by bone marrow-derived mesenchymal stem cells grown in chondrocyte conditioned medium for auricular reconstruction. AB - Bone marrow-derived mesenchymal stem cells (BMSCs) can be obtained by minimally invasive means and would be a favourable source for cell-based cartilage regeneration. However, controlling the differentiation of the BMSCs towards the desired chondrogenic pathway has been a challenge hampering their application. The major aim of the present study was to determine if conditioned medium collected from cultured auricular chondrocytes could promote chondrogenic differentiation of BMSCs. Auricular chondrocytes were isolated and grown in BMSC standard culture medium (SM) that was collected and used as chondrocyte conditioned medium (CCM). The BMSCs were expanded in either CCM or SM for three passages. Cells were seeded onto fibrous collagen scaffolds and precultured for 2 weeks with or without transforming growth factor-beta 3 (TGF-beta3). After preculture, constructs were implanted subcutaneously in nude mice for 6 and 12 weeks and evaluated with real-time polymerase chain reaction, histology, immunohistochemistry and biochemistry. Real-time polymerase chain reaction results showed upregulation of COL2A1 in the constructs cultured in CCM compared with those in SM. After 12 weeks in vivo, abundant neocartilage formation was observed in the implants that had been cultured in CCM, with or without TGF beta3. In contrast, very little cartilage matrix formation was observed within the SM groups, regardless of the presence of TGF-beta3. Osteogenesis was only observed in the SM group with TGF-beta3. In conclusion, CCM even had a stronger influence on chondrogenesis than the supplementation of the standard culture medium with TGF-beta3, without signs of endochondral ossification. Efficient chondrogenic differentiation of BMSCs could provide a promising alternative cell population for auricular regeneration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27256798 TI - Bone carrier technique with disposable syringe. PMID- 27256799 TI - Guerin sign in midfacial fractures. AB - We report a patient with multiple fractures of the midface and Guerin sign bilaterally after maxillofacial trauma. To the best of our knowledge, this is the first time that this rare presentation of Guerin sign has been published. PMID- 27256800 TI - Third molar consent forms: how comprehensive should they be? AB - To establish a gold standard for the information given to patients about the risks associated with third molar extractions, we surveyed 79 oral and maxillofacial surgeons (OMFS) to find out what information they gave to patients during the consent process. We also surveyed 62 medicolegal solicitors to find out what information they thought patients should be given before the procedure, and in what form. A total of 20/76 OMFS (26%) used a two-stage process to obtain consent; 13 (17%) included paraesthesia on the consent form and also gave out an information leaflet. All the lawyers agreed that patients should give their consent in writing and thought that the risk of paraesthesia should be included on the form. Three-quarters thought that they should also be given an information leaflet that includes paraesthesia. We encourage surgeons to do this as part of the two-stage consent process. PMID- 27256801 TI - Coronectomy of mandibular teeth other than third molars: a case series. AB - Coronectomy is gaining popularity for the management of mandibular third molars that pose a risk of injury to the inferior dental nerve, as it considerably reduces the risk when compared with extraction. The technique could also be beneficial to other teeth. We report 17 patients who had coronectomy of mandibular teeth that were not third molars. Clinical and radiographic follow up for a median (range) of 12 (1-79) months showed satisfactory healing and no transient or permanent injury to the nerve. None of the retained roots have required retrieval. PMID- 27256802 TI - Botulinum toxin used to treat recurrent dislocation of the temporomandibular joint in a patient with osteoporosis. AB - Recurrent dislocations of the temporomandibular joint (TMJ) can be debilitating. We describe a patient with osteoporosis who presented to our regional centre where we have limited resources. We injected botulinum toxin into both of her lateral pterygoid muscles, and six months later she has not required further injections and has had no issues with tolerance of the procedure. Botulinum toxin is a safe, conservative approach to recurrent dislocations of the TMJ and can be given accurately by an experienced surgeon without the use of an electromyogram. PMID- 27256803 TI - Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia. AB - Mutations resulting in constitutive activation of signaling pathways that regulate ribosome biogenesis are among the most common genetic events in acute myeloid leukemia (AML). However, whether ribosome biogenesis presents as a therapeutic target to treat AML remains unexplored. Perturbations in ribosome biogenesis trigger the 5S ribonucleoprotein particle (RNP)-Mdm2-p53 ribosomal stress pathway, and induction of this pathway has been shown to have therapeutic efficacy in Myc-driven lymphoma. In the current study we address the physiological and therapeutic role of the 5S RNP-Mdm2-p53 pathway in AML. By utilizing mice that have defective ribosome biogenesis due to downregulation of ribosomal protein S19 (Rps19), we demonstrate that induction of the 5S RNP-Mdm2 p53 pathway significantly delays the initiation of AML. However, even a severe Rps19 deficiency that normally results in acute bone marrow failure has no consistent efficacy on already established disease. Finally, by using mice that harbor a mutation in the Mdm2 gene disrupting its binding to 5S RNP, we show that loss of the 5S RNP-Mdm2-p53 pathway is dispensable for development of AML. Our study suggests that induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway holds limited potential as a single-agent therapy in the treatment of AML. PMID- 27256804 TI - Hypolipidemic and antioxidant effects of ethanol extract of Cassia fistula fruit in hyperlipidemic mice. AB - CONTEXT: The plant Cassia fistula L. (Caesalpiniaceae) fruit was widely used by traditional practitioners to treat cardiovascular diseases (CVDs) in India. Hyperlipidemia is a lipid metabolism disorder and the major risk factor for the development of CVDs. Although most of the current hypolipidemic drugs are expensive and have potential side effects, the research focusing on natural alternative medicines is relevant. OBJECTIVE: To investigate the hypolipidemic and antioxidant effects of ethanol extract of C. fistula fruit (CFE) in high-fat diet (HFD) induced hyperlipidemia in mice. MATERIALS AND METHODS: Oral administration of CFE at 100, 300 and 500 mg/kg body weight on HFD induced hyperlipidemia mice for 30 days. The standard drug atorvastatin (20 mg/kg) was used to compare the efficacy of CFE. Hypolipidemic effect was evidenced by the measurement of serum lipid profile and further confirmed by Oil Red O staining of adipose tissue. The hepatic and cardiac melondialdehyde (MDA) level and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase were determined. RESULTS: Treatment with CFE at different doses has significantly restored the levels of serum lipid, MDA and enzymes activities in the liver and heart of hyperlipidemia mice. Oil Red O staining of visceral adipose tissue has shown marked reduction of lipid accumulation in adipocytes; whereas, administration of CFE at 500 mg/kg showed remarkable (p < 0.001) hypolipidemic and antioxidant effects in HFD fed mice. CONCLUSION: C. fistula fruit demonstrated hypolipidemic and antioxidant properties in vivo and the results corroborate the use of this plant in traditional medicine for cardiac ailments. PMID- 27256805 TI - Nanomechanical probing of the layer/substrate interface of an exfoliated InSe sheet on sapphire. AB - Van der Waals (vdW) layered crystals and heterostructures have attracted substantial interest for potential applications in a wide range of emerging technologies. An important, but often overlooked, consideration in the development of implementable devices is phonon transport through the structure interfaces. Here we report on the interface properties of exfoliated InSe on a sapphire substrate. We use a picosecond acoustic technique to probe the phonon resonances in the InSe vdW layered crystal. Analysis of the nanomechanics indicates that the InSe is mechanically decoupled from the substrate and thus presents an elastically imperfect interface. A high degree of phonon isolation at the interface points toward applications in thermoelectric devices, or the inclusion of an acoustic transition layer in device design. These findings demonstrate basic properties of layered structures and so illustrate the usefulness of nanomechanical probing in nanolayer/nanolayer or nanolayer/substrate interface tuning in vdW heterostructures. PMID- 27256806 TI - Evidence and Access to Biomedical Interventions: The Case of Stem Cell Treatments. AB - The controversy over patients' access to stem cell interventions is familiar to scholars of the drug regulatory system and the politics of evidence-based medicine. What counts as evidence of a biomedical intervention's safety and effectiveness? Who should define and assess safety and effectiveness, and how? In the first section of the paper we describe the types of stem cells that may be therapeutically effective. We then describe how the US Food and Drug Administration asserted regulatory authority over certain stem cell interventions and the legal challenge to the agency's actions. Next, we place the debate about patients' access to stem cell interventions in the broader context of efforts in the US to promote and implement health technology assessment and the debate about standards of evidence. We then review several proposed initiatives to get stem cell and other new biomedical interventions into the clinic faster and consider the extent to which these policies can resolve the underlying conflicts about evidentiary standards for clinical use. Finally, we consider whether efforts to expedite access to biomedical technologies may undermine countervailing efforts to improve the safety and effectiveness of stem cell interventions. PMID- 27256807 TI - Medicaid Expansion: A Tale of Two Governors. AB - This is a study of why two seemingly similar governors made divergent decisions on expanding Medicaid under the Patient Protection and Affordable Care Act (ACA). Performing a case study of Governors John Kasich (OH) and Scott Walker (WI), I explore the roles played by electoral pressures, political party, governor's ideology, the state's policy heritage, stakeholder advocacy, and the economy in each governor's decision about whether to expand Medicaid. Electoral pressure was the most significant factor for both governors. I demonstrate that even Walker succumbed to state electoral pressures and expanded Medicaid, albeit in a manner unique to Wisconsin. He did this despite his emphatic national rhetoric rejecting Obamacare and expansion. Additionally, existing state political institutions drove each governor to decide in a manner unique to his state: previous Medicaid decisions in Wisconsin and direct democracy in Ohio provided additional pressures and divergent starting points. The remaining factors served less as a driving force behind the decision and more as a frame to justify the decision ex post facto. Case studies allow for a more complex view of how political pressures fit together; differences can be explained and expanded, and an enhanced understanding of political processes can be gleaned. PMID- 27256808 TI - What Is the Value of Value-Based Purchasing? AB - Value-based purchasing (VBP) is a widely favored strategy for improving the US health care system. The meaning of value that predominates in VBP schemes is (1) conformance to selected process and/or outcome metrics, and sometimes (2) such conformance at the lowest possible cost. In other words, VBP schemes choose some number of "quality indicators" and financially incent providers to meet them (and not others). Process measures are usually based on clinical science that cannot determine the effects of a process on individual patients or patients with comorbidities, and do not necessarily measure effects that patients value; additionally, there is no provision for different patients valuing different things. Proximate outcome measures may or may not predict distal ones, and the more distal the outcome, the less reliably it can be attributed to health care. Outcome measures may be quite rudimentary, such as mortality rates, or highly contestable: survival or function after prostate surgery? When cost is an element of value-based purchasing, it is the cost to the value-based payer and not to other payers or patients' families. The greatest value of value-based purchasing may not be to patients or even payers, but to policy makers seeking a morally justifiable alternative to politically contested regulatory policies. PMID- 27256809 TI - Market Conditions and Performance in the Nursing Home Compare Five-Star Rating. AB - Previous studies have documented that market conditions affect nursing home performance; however, the evidence is inconsistent and conflicting. This study introduces three groups of county market conditions and a peer effect variable, and tests their impacts on the Nursing Home Compare (NHC) Five-Star overall rating. Indiana nursing home data and county characteristics are taken mainly from the NHC and Census Bureau websites. The result of the ordered logistic regression analysis indicates that nursing homes in excess demand markets, namely those that are highly concentrated and have fewer nursing homes, tend to perform better than their counterparts in both excess supply and balanced markets. In addition, a peer effect variable, measured as the average overall rating of the competitors, promotes performance improvement. These findings imply that small markets enable consumers to be well informed about a provider's reputation for quality, consequently enhancing performance. Furthermore, not only consumers but also providers seem to seek performance information on the report card to understand their relative position in the market, which thus affects their market strategies and subsequently performance. PMID- 27256810 TI - A Corporate Veto on Health Policy? Global Constitutionalism and Investor-State Dispute Settlement. AB - The importance of trade and investment agreements for health is now widely acknowledged in the literature, with much attention now focused on the impact of investor-state dispute settlement (ISDS) mechanisms. However, much of the analysis of such agreements in the health field remains largely descriptive. We theorize the implications of ISDS mechanisms for health policy by integrating the concept of global constitutionalism with veto point theory. It is argued that attempts to constitutionalize investment law, through a proliferation of International Investment Agreements (IIAs), has created a series of new veto points at which corporations may seek to block new policies aimed at protecting or enhancing public health. The multiplicity of new veto points in this global "spaghetti bowl" of IIAs creates opportunities for corporations to venue shop; that is, to exploit the agreements, and associated veto points, through which they are most likely to succeed in blocking or deterring new regulation. These concepts are illustrated with reference to two case studies of investor-state disputes involving a transnational tobacco company, but the implications of the analysis are of equal relevance for a range of other industries and health issues. PMID- 27256811 TI - Effects of Competing Narratives on Public Perceptions of Opioid Pain Reliever Addiction during Pregnancy. AB - Opioid pain reliever addiction has increased among women of reproductive age over the last fifteen years. News media and public attention have focused on the implications of this trend for infants exposed to opioids prenatally, with state policy responses varying in the extent to which they are punitive or public health oriented. We fielded a six-group randomized experiment among a nationally representative sample of US adults to test the effects of narratives portraying a woman with opioid pain reliever addiction during pregnancy on beliefs about people addicted to opioid pain relievers, perceptions of treatment effectiveness, policy attitudes, and emotional responses. Portraying a high socioeconomic status (SES) woman in the narrative lowered perceptions of individual blame for addiction and reduced public support for punitive policies. Depicting the barriers to treatment faced by a low SES woman lowered support for punitive policies and increased support for expanded insurance coverage for treatment. The extent to which narratives portraying successfully treated addiction affected public attitudes depended on the SES of the woman portrayed. These findings can inform the development of communication strategies to reduce stigma toward this population, reduce support for punitive policies, and increase support for more public health-oriented approaches to addressing this problem. PMID- 27256813 TI - Imaging mass spectrometry for accessing molecular changes during burn wound healing. AB - The spatiotemporal analysis of the proteomic profile during human wound healing is a critical investigative step that can establish the complex interplay of molecular events that comprise the local response to burn injury. Partial thickness wound samples with adjacent "normal" skin were collected from twenty one patients with burn wounds and examined across a time spectrum ranging from the acute injury period at 3, 6, 11 days to the later hypertrophic scar period at 7 and 15 months. The techniques used for histology-directed tissue analyses highlighted inflammatory protein markers at the early time points after injury with diminished expression as burn wounds progressed into the proliferative phase. The datasets show the usefulness of MALDI MS and imaging mass spectrometry as discovery approaches to identify and map the cutaneous molecular sequence that is activated in response to the unique systemic inflammatory response following burn trauma. This information has the potential to define the unique factors that predispose human burn victims to disfiguring hypertrophic scar formation. PMID- 27256812 TI - Pharmacokinetic Evaluation of a Drug Transporter Cocktail Consisting of Digoxin, Furosemide, Metformin, and Rosuvastatin. AB - This article reports the clinical investigation of a probe drug cocktail containing substrates of key drug transporters. Single oral doses of 0.25 mg digoxin (P-gp), 5 mg furosemide (OAT1 and OAT3), 500 mg metformin (OCT2, MATE1, and MATE2-K), and 10 mg rosuvastatin (OATP1B1, OATP1B3, and BCRP) were administered separately or as a cocktail in a randomized six-period crossover trial in 24 healthy male volunteers. As a cocktail, relative bioavailabilities of digoxin and metformin and furosemide AUC0-tz were similar to separate dosing. However, when administered as a cocktail the Cmax of furosemide was 19.1% lower and the Cmax and AUC0-tz of rosuvastatin were 38.6% and 43.4% higher, respectively. In addition, the effects of increased doses of metformin or furosemide on the cocktail were investigated in 11 and 12 subjects, respectively. The cocktail explored in this trial has the potential to be used for the in vivo screening of transporter-mediated drug-drug interactions. (c) 2016 American Society for Clinical Pharmacology and Therapeutics. PMID- 27256814 TI - Relative Brain Size Is Not Correlated with Display Complexity in Manakins: A Reanalysis of Lindsay et al. (2015). PMID- 27256816 TI - Women's Lifestyle Physical Activity Program for African American Women: Fidelity Plan and Outcomes. AB - BACKGROUND: For interventions to be implemented effectively, fidelity must be documented. We evaluated fidelity delivery, receipt, and enactment of the 48-week Women's Lifestyle Physical Activity Program conducted to increase physical activity and maintain weight in African American women. METHODS: Three study conditions all received 6 group meetings; 1 also received 11 motivational interviewing personal calls (PCs), 1 received11 automated motivational message calls (ACs), and 1 received no calls. Group meeting delivery was assessed for adherence and competence. PC delivery was assessed with the Motivational Interviewing Treatment Integrity Code. Receipt was defined as group meeting attendance, completion of PCs, and listening to ACs. Enactment was number of weeks an accelerometer was worn. RESULTS: For group meeting delivery, mean adherence was 80.8% and mean competence 2.9 of 3.0. Delivery of PCs did not reach criterion for competence. Receipt of more than one-half the dose was achieved for 84.9% of women for group meetings, 85.5% for PCs, and 42.1% for ACs. Higher group meeting attendance was associated with higher accelerometer steps at 24 weeks and lower BMI at 24 and 48 weeks. CONCLUSIONS: Fidelity measurement and examination of intervention delivery, receipt, and enactment are important to explicate conditions in which interventions are successful. PMID- 27256817 TI - Editorial: Older Driver Research. Evidence to Guide Change. PMID- 27256815 TI - Divergence and Conservation of the Major UPR Branch IRE1-bZIP Signaling Pathway across Eukaryotes. AB - The unfolded protein response (UPR) is crucial to life by regulating the cellular response to the stress in the endoplasmic reticulum (ER) imposed by abiotic and biotic cues such as heat shock and viral infection. The inositol requiring enzyme 1 (IRE1) signaling pathway activated by the IRE1-mediated unconventional splicing of HAC1 in yeast, bZIP60 in plants and XBP1 in metazoans, is the most ancient branch of the UPR. In this study, we systematically examined yeast IRE1p-HAC1, plant IRE1A/IRE1B-bZIP60 and human hIRE1-XBP1 pairs. We found that, unlike bZIP60, XBP1 is unable to functionally swap HAC1p in yeast, and that the inter species heterotypic interactions among HAC1p, bZIP60 and XBP1 are not permitted. These data demonstrate evolutionary divergence of the downstream signaling of IRE1-bZIP. We also discovered that the dual cytosolic domains of plant IRE1s act in vivo in a mechanism consistent with IRE1p and hIRE1, and that plant IRE1B not only interacts with IRE1p but also forms typical IRE1 dynamic foci in yeast. Thus, the upstream components of the IRE1 signaling branch including IRE1 activation and action mechanisms are highly conserved. Taken together these data advance the molecular understanding of evolutionary divergence and conservation of the IRE1 signaling pathway across kingdoms. PMID- 27256818 TI - [Editorial : Recherche sur la conduite automobile des personnes agees : des preuves afin de guider le changement]. PMID- 27256819 TI - Attitudes: Mediators of the Relation between Health and Driving in Older Adults. AB - We examined the relations between perceived health (e.g., self-perceived health status) and driving self-regulatory practices (e.g., frequency of driving, avoiding challenging driving situations) as mediated by driving attitudes and perceptions (i.e., driving comfort, positive and negative attitudes towards driving) in data collected for 928 drivers aged 70 and older enrolled in the Candrive II study. We observed that specific attitudes towards driving (e.g., driving comfort, negative attitudes towards driving) mediate the relations between health symptoms and self-regulatory driving behaviours at baseline and over time. Only negative attitudes towards driving fully mediated the relationships between changes in perceived health symptoms and changes in driving behavior. Perceived health symptoms apparently influence the likelihood of avoiding challenging driving situations through both initial negative attitudes towards driving as well as changes in negative attitudes over time. Understanding influences on self-regulatory driving behaviours will be of benefit when designing interventions to enhance the safety of older drivers. PMID- 27256820 TI - CIHR Candrive Cohort Comparison with Canadian Household Population Holding Valid Driver's Licenses. AB - We investigated whether convenience sampling is a suitable method to generate a sample of older drivers representative of the older-Canadian driver population. Using equivalence testing, we compared a large convenience sample of older drivers (Candrive II prospective cohort study) to a similarly aged population of older Canadian drivers. The Candrive sample consists of 928 community-dwelling older drivers from seven metropolitan areas of Canada. The population data was obtained from the Canadian Community Health Survey - Healthy Aging (CCHS-HA), which is a representative sample of older Canadians. The data for drivers aged 70 and older were extracted from the CCHS-HA database, for a total of 3,899 older Canadian drivers. Two samples were demonstrated as equivalent on socio demographic, health, and driving variables that we compared, but not on driving frequency. We conclude that convenience sampling used in the Candrive study created a fairly representative sample of Canadian older drivers, with a few exceptions. PMID- 27256821 TI - How is renal function 45 years after SCI? PMID- 27256822 TI - Text input speed in persons with cervical spinal cord injury. PMID- 27256823 TI - Forty-five-year follow-up on the renal function after spinal cord injury. PMID- 27256824 TI - Predictors of outcome for urethral injection of botulinum toxin to treat detrusor sphincter dyssynergia in men with spinal cord injury. PMID- 27256826 TI - North Atlantic Deep Water Production during the Last Glacial Maximum. AB - Changes in deep ocean ventilation are commonly invoked as the primary cause of lower glacial atmospheric CO2. The water mass structure of the glacial deep Atlantic Ocean and the mechanism by which it may have sequestered carbon remain elusive. Here we present neodymium isotope measurements from cores throughout the Atlantic that reveal glacial-interglacial changes in water mass distributions. These results demonstrate the sustained production of North Atlantic Deep Water under glacial conditions, indicating that southern-sourced waters were not as spatially extensive during the Last Glacial Maximum as previously believed. We demonstrate that the depleted glacial delta(13)C values in the deep Atlantic Ocean cannot be explained solely by water mass source changes. A greater amount of respired carbon, therefore, must have been stored in the abyssal Atlantic during the Last Glacial Maximum. We infer that this was achieved by a sluggish deep overturning cell, comprised of well-mixed northern- and southern-sourced waters. PMID- 27256827 TI - Use of smokeless tobacco and risk of cardiovascular disease: A systematic review and meta-analysis. AB - Objective The purpose of this study was to assess the risk of ischaemic heart disease (IHD) and stroke (non-fatal and fatal) among adult ever-users of smokeless tobacco (ST). Design The study design involved a systematic review and meta-analysis of observational studies. Methods Data sources for the review included key electronic databases and reference lists. Studies were included based on design (cohort or case-control), exposure (exclusive use of ST or adjusted for smoking), and outcome (non-fatal and fatal IHD and stroke). Data extraction included reported measures of association (risk ratios (RRs) or odds ratios (ORs)) between ever-use of ST (current or past) and cardiovascular disease (CVD) outcomes among non-smokers, and other study characteristics. The Newcastle Ottawa scale was used to assess study quality. Summary measures were estimated using random effects models. Results Twenty studies were included in the meta analyses. Overall, significantly increased risk of IHD deaths (1.15, 95% confidence interval (CI: 1.01-1.30) and stroke deaths (1.39, 95% CI: 1.29-1.49) was found among ever-users of ST. We did not find an overall significant increased risk for IHD (1.14, 95% CI: 0.92-1.42) or stroke (1.01, 95% CI: 0.90 1.13). But geographical variations were marked for IHD, with significant positive association in Asian studies (1.40, 95% CI: 1.01-1.95), and the INTERHEART study, where ST data was mainly reported from Asia (2.23, 95% CI: 1.41-3.53). European studies did not show an increased risk for non-fatal CVD. Conclusion An association was found between ever use of ST and risk of fatal IHD and stroke, consistent with previous reviews. ST consumption also appears to significantly increase risk of non-fatal IHD among users in Asia, but not in Europe. PMID- 27256825 TI - Thyroid function and cardiovascular disease risk factors in euthyroid adults: a cross-sectional and longitudinal study. AB - OBJECTIVE AND DESIGN: We explored the cross-sectional and longitudinal associations of thyroid function within the normal range with cardiovascular disease (CVD) risk factors and adiposity measures. PATIENTS AND MEASUREMENTS: A total of 3483 (50.4% women) participants for the cross-sectional CVD study and 1630 (41.2% women) participants for the cross-sectional body composition substudy were drawn from the Framingham Third Generation Exam 1; 2912 participants (50.1% women) for the longitudinal CVD study and 713 participants (35.9% women) for the longitudinal body composition substudy were drawn from the Framingham Third Generation Exams 1-2. Thyroid function was assessed by thyrotropin [thyroid stimulating hormone (TSH)] and free thyroxine (fT4) concentrations within the reference range at Exam 1. The associations between thyroid function and CVD risk factors were modelled via multivariable-adjusted regression models. Multivariable adjustment included age, sex, current smoking, postmenopausal status and BMI. RESULTS: Cross-sectionally, higher TSH concentration was associated with increased odds of hypertriglyceridaemia [odds ratio (OR)=1.10], and higher BMI (beta = 0.19 kg/m2 ), total cholesterol (beta = 0.05 mmol/l), triglycerides (beta = 0.0006 mmol/l) and subcutaneous adipose tissue (SAT) volume (beta = 38.8 cm3 ) (all P < 0.05). Cross-sectionally, fT4 was inversely associated with metabolic and adiposity-related CVD risk factors, including obesity (OR = 1.17), hypertriglyceridaemia (OR = 1.09), BMI (beta = 0.42 kg/m2 ), total cholesterol (beta = 0.05 mmol/l), triglycerides (beta = 0.0002 mmol/l), visceral adipose tissue (VAT) volume (beta = -20.7 cm3 ) and attenuation (0.17 HU) and VAT/SAT ratio (beta = -0.01) (all P < 0.05). However, during 6.1 years of follow-up, baseline TSH and fT4 levels were not longitudinally associated with CVD risk factors and adiposity measures. CONCLUSIONS: Thyroid function within the normal range is cross-sectionally, but not longitudinally, associated with CVD risk factors and adiposity measures. PMID- 27256828 TI - Screening for atrial fibrillation in primary care: From recommendation to implementation. PMID- 27256829 TI - A Comparison of the Selectivity of Extraction of [PtCl6](2-) by Mono-, Bi-, and Tripodal Receptors That Address Its Outer Coordination Sphere. AB - Extraction and binding studies of [PtCl6](2-) are reported for 24 mono-, bi-, and tripodal extractants containing tris(2-aminoethyl)amine (TREN) or tris(3 aminopropyl)amine (TRPN) scaffolds. These reagents are designed to recognize the outer coordination sphere of [PtCl6](2-) and to show selectivity over chloride anion under acidic conditions. Extraction from 0.6 M HCl involves protonation of the N-center in tertiary amines containing one, two, or three urea, amide, or sulfonamide hydrogen-bond donors to set up the following equilibrium: 2L(org) + 2H(+) + [PtCl6](2-) ? [(LH)2PtCl6](org). All reagents show higher Pt loading than trioctylamine, which was used as a positive control to represent commercial trialkylamine reagents. The loading of [PtCl6](2-) depends on the number of pendant amides in the extractant and follows the order tripodal > bipodal > monopodal, with urea-containing extractants outperforming amide and sulfonamide analogues. A different series of reagents in which one, two, or three of the alkyl groups in tris-2-ethylhexylamine are replaced by 3-N'-hexylpropanamide groups all show a comparably high affinity for [PtCl6](2-) and high selectivity over chloride anion in extractions from aqueous acidic solutions. (1)H NMR titration of three extractants [LH.Cl] with [(Oct4N)2PtCl6] in CDCl3 provides evidence for high selectivity for [PtCl6](2-) over chloride for tri- and bipodal extractants, which show higher binding constants than a monopodal analogue. PMID- 27256830 TI - Familial Hypercholesterolemia: Now Part of Cardiovascular Disease Genetic Epidemiology Research. PMID- 27256831 TI - Looking for a Brighter Future in Heart Failure: A Role for Vitamin D Supplementation? PMID- 27256832 TI - Diagnostic Algorithms for Stable Chest Pain: From Opinion to Science Lessons From PROMISE. PMID- 27256834 TI - Can Fishy Odor Be a Risk Factor for Coronary Artery Disease? PMID- 27256833 TI - Plasma Trimethylamine N-Oxide, a Gut Microbe-Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden. AB - BACKGROUND: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is associated with adverse outcomes. OBJECTIVES: This study sought to examine the relationship between plasma TMAO levels and the complexity and burden of CAD and degree of subclinical myonecrosis. METHODS: We studied 353 consecutive stable patients with evidence of atherosclerotic CAD detected by elective coronary angiography between 2012 and 2014. Their high-sensitivity cardiac troponin T (hs-cTnT) levels were measured. SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) scores and lesion characteristics were used to quantify atherosclerotic burden. Fasting plasma TMAO was measured by mass spectrometry. RESULTS: In this prospective cohort study, the median TMAO level was 5.5 MUM (interquartile range [IQR]: 3.4 to 9.8 MUM), the median SYNTAX score was 11.0 (IQR: 4.0 to 18.5), and 289 (81.9%), 40 (11.3%), and 24 (6.8%) patients had low (0 to 22), intermediate (23 to 32), and high (>=33) SYNTAX scores, respectively. Plasma TMAO levels correlated (all p < 0.0001) with the SYNTAX score (r = 0.61), SYNTAX score II (r = 0.62), and hs-cTnT (r = 0.29). Adjusting for traditional risk factors, body mass index, medications, lesion characteristic, renal function, and high sensitivity C-reactive protein, elevated TMAO levels remained independently associated with a higher SYNTAX score (odds ratio [OR]: 4.82; p < 0.0001), SYNTAX score II (OR: 1.88; p = 0.0001), but were not associated with subclinical myonecrosis (OR: 1.14; p = 0.3147). Elevated TMAO level was an independent predictor of the presence of diffuse lesions, even after adjustments for traditional risk factors and for hs-cTnT (OR: 2.05; 95% confidence interval: 1.45 to 2.90; p = 0.0001). CONCLUSIONS: Fasting plasma TMAO levels are an independent predictor of a high atherosclerotic burden in patients with CAD. PMID- 27256835 TI - Acute Ischemic Stroke Intervention. AB - Acute ischemic stroke (AIS) is the leading cause of disability worldwide and among the leading causes of mortality. Although intravenous tissue plasminogen activator (IV-rtPA) was approved nearly 2 decades ago for treatment of AIS, only a minority of patients receive it due to a narrow time window for administration and several contraindications to its use. Endovascular approaches to recanalization in AIS developed in the 1980s, and recently, 5 major randomized trials showed an overwhelming superior benefit of combining endovascular mechanical thrombectomy with IV-rtPA over IV-rtPA alone. In this paper, we discuss the evolution of catheter-based treatment from first-generation thrombectomy devices to the game-changing stent retrievers, results from recent trials, and the evolving stroke systems of care to provide timely access to acute stroke intervention to patients in the United States. PMID- 27256836 TI - Recent Endovascular Stroke Trials and Their Impact on Stroke Systems of Care. AB - Five recently published randomized trials of endovascular therapy versus medical management, including intravenous thrombolysis, demonstrated strong positive data in support of intra-arterial thrombectomy procedures. The American Heart Association/American Stroke Association released a focused update of the 2013 guidelines on the early management of acute ischemic strokes to specifically incorporate the findings of the 5 "positive" trials. In this review, we examine the key results of those trials and the principal changes in the updated guidelines. We discuss the ongoing and future changes in stroke systems of care, with an emphasis on the role of pre-hospital stroke triage, interhospital transfer, and the 2 main levels of stroke center certification (primary and comprehensive). PMID- 27256837 TI - Technical Performance Score Predicts Resource Utilization in Congenital Cardiac Procedures. PMID- 27256838 TI - Ischemia and Infarction in STEMI Patients With Multivessel Disease: Insights From the CvLPRIT Nuclear Substudy. PMID- 27256839 TI - Persistent Atrial Fibrillation: Time to Stop Comparing Apples With Oranges. PMID- 27256840 TI - Atrial Fibrillation: Beyond the Pulmonary Veins. PMID- 27256841 TI - Reply: Persistent Atrial Fibrillation: Time to Stop Comparing Apples With Oranges: Atrial Fibrillation: Beyond the Pulmonary Veins. PMID- 27256842 TI - Intraluminal Scaffold Dismantling: The Downside of Positive Remodeling? PMID- 27256843 TI - Reply: Intraluminal Scaffold Dismantling: The Downside of Positive Remodeling? PMID- 27256844 TI - Influence of foot-stretcher height on rowing technique and performance. AB - Strength, technique, and coordination are crucial to rowing performance, but external interventions such as foot-stretcher set-up can fine-tune technique and optimise power output. For the same resultant force, raising the height of foot stretchers on a rowing ergometer theoretically alters the orientation of the resultant force vector in favour of the horizontal component. This study modified foot-stretcher heights and examined their instantaneous effect on foot forces and rowing technique. Ten male participants rowed at four foot-stretcher heights on an ergometer that measured handle force, stroke length, and vertical and horizontal foot forces. Rowers were instrumented with motion sensors to measure ankle, knee, hip, and lumbar-pelvic kinematics. Key resultant effects of increased foot-stretcher heights included progressive reductions in horizontal foot force, stroke length, and pelvis range of motion. Raising foot-stretcher height did not increase the horizontal component of foot force as previously speculated. The reduced ability to anteriorly rotate the pelvis at the front of the stroke may be a key obstacle in gaining benefits from raised foot-stretcher heights. This study shows that small changes in athlete set-up can influence ergometer rowing technique, and rowers must individually fine-tune their foot stretcher height to optimise power transfer through the rowing stroke on an ergometer. PMID- 27256845 TI - Radiation recall dermatitis induced by topical tacrolimus for post-irradiation morphea. PMID- 27256846 TI - The BRPF2/BRD1-MOZ complex is involved in retinoic acid-induced differentiation of embryonic stem cells. AB - The scaffold protein BRPF2 (also called BRD1), a key component of histone acetyltransferase complexes, plays an important role in embryonic development, but its function in the differentiation of embryonic stem cells (ESCs) remains unknown. In the present study, we investigated whether BRPF2 is involved in mouse ESC differentiation. BRPF2 depletion resulted in abnormal formation of embryoid bodies, downregulation of differentiation-associated genes, and persistent maintenance of alkaline phosphatase activity even after retinoic acid-induced differentiation, indicating impaired differentiation of BRPF2-depleted ESCs. We also found reduced global acetylation of histone H3 lysine 14 (H3K14) in BRPF2 depleted ESCs, irrespective of differentiation status. Further, co immunoprecipitation analysis revealed a physical association between BRPF2 and the histone acetyltransferase MOZ in differentiated ESCs, suggesting the role of BRPF2-MOZ complexes in ESC differentiation. Together, these results suggest that BRPF2-MOZ complexes play an important role in the differentiation of ESCs via H3K14 acetylation. PMID- 27256847 TI - Keeping it Ethically Real. AB - Many clinical ethicists have argued that ethics expertise is impossible. Their skeptical argument usually rests on the assumptions that to be an ethics expert is to know the correct moral conclusions, which can only be arrived at by having the correct ethical theories. In this paper, I argue that this skeptical argument is unsound. To wit, ordinary ethical deliberations do not require the appeal to ethical or meta-ethical theories. Instead, by agreeing to resolve moral differences by appealing to reasons, the participants agree to the Default Principle-a substantive rule that tells us how to adjudicate an ethical disagreement. The Default Principle also entails a commitment to arguments by parity, and together these two methodological approaches allow us to make genuine moral progress without assuming any deep ethical principles. Ethical expertise, in one sense, is thus the ability and knowledge to deploy the Default Principle and arguments by parity. PMID- 27256848 TI - Expertise, Ethics Expertise, and Clinical Ethics Consultation: Achieving Terminological Clarity. AB - The language of ethics expertise has become particularly important in bioethics in light of efforts to establish the value of the clinical ethics consultation (CEC), to specify who is qualified to function as a clinical ethics consultant, and to characterize how one should evaluate whether or not a person is so qualified. Supporters and skeptics about the possibility of ethics expertise use the language of ethics expertise in ways that reflect competing views about what ethics expertise entails. We argue for clarity in understanding the nature of expertise and ethics expertise. To be an ethics expert, we argue, is to be an expert in knowing what ought to be done. Any attempt to articulate expertise with respect to knowing what ought to be done must include an account of ethics that specifies the nature of moral truth and the means by which we access this truth or a theoretical account of ethics such that expertise in another domain is linked to knowing or being better at judging what ought to be done and the standards by which this "knowing" or "being better at judging" is determined. We conclude with a discussion of the implications of our analysis for the literature on ethics expertise in CEC. We do think that there are clear domains in which a clinical ethics consultant might be expert but we are skeptical about the possibility that this includes ethics expertise. Clinical ethics consultants should not be referred to as ethics experts. PMID- 27256849 TI - Flow Diversion for Ophthalmic Artery Aneurysms. AB - Endovascular treatments of ophthalmic segment aneurysms are commonly used but visual outcomes remain a concern. We performed a retrospective review of patients with carotid-ophthalmic aneurysms treated with flow diversion from June 2009 to June 2015. The following outcomes were studied through chart review: visual outcomes, complications, postoperative stroke and intraparenchymal hemorrhage, and clinical outcomes. Angiographic outcomes were studied with angiography and MRA at 6 months, 1 year, and 3 years. We evaluated 50 carotid-ophthalmic aneurysms in 48 patients, among whom 44 patients with 46 aneurysms underwent treatment. The mean clinical follow-up was 29 +/- 22 months (range, 0-65 months). There were no permanent adverse visual outcomes. There was 1 death because of late intraparenchymal hemorrhage (2.2%). Six-month angiography showed complete occlusion in 24 of 37 patients (64.9%), and 3-year angiography results showed occlusion in 24 of 25 patients (96%). In conclusion, flow diversion is a safe and effective treatment for carotid-ophthalmic aneurysms in carefully selected patients. The risk of adverse visual outcomes is low, and most aneurysms progress to complete occlusion. PMID- 27256850 TI - Endovascular Coiling of Wide-Neck and Wide-Neck Bifurcation Aneurysms: A Systematic Review and Meta-Analysis. AB - BACKGROUND AND PURPOSE: We present the results of a systematic review and meta analysis examining outcomes of endovascular coiling of wide-neck and wide-neck bifurcation aneurysms with and without stent assistance. The aim of our study was to assess angiographic and clinical outcomes. MATERIALS AND METHODS: We performed a comprehensive literature search for all articles on the endovascular coiling of wide-neck and wide-neck bifurcation aneurysms. Studies meeting our inclusion criteria and abstracted data were selected by 2 independent reviewers. Primary outcomes were >6-month complete or near-complete angiographic occlusion, aneurysm recanalization, and aneurysm retreatment. Secondary outcomes included initial complete or near-complete occlusion, long-term good neurologic outcome, procedure related morbidity, and procedure-related mortality. Data were analyzed by using random-effects meta-analysis. RESULTS: In total, 38 studies including 2446 patients with 2556 aneurysms were included. For all wide-neck aneurysms, immediate complete or near-complete occlusion rate was 57.4% (95% CI, 48.1% 66.8%). Follow-up near-complete occlusion rate was 74.5% (95% CI, 68.0%-81.0%). Recanalization and retreatment rates were 9.4% (95% CI, 7.1%-11.7%) and 5.8% (95% CI, 4.1%-7.5%), respectively. Long-term good neurologic outcome was 91.4% (95% CI, 88.5%-94.2%). For wide-neck bifurcation aneurysms, initial complete or near complete occlusion rate was 60.0% (95% CI, 42.7%-77.3%), long-term complete or near-complete occlusion rate was 71.9% (95% CI, 52.6%-91.1%), and the recanalization and retreatment rates were 9.8% (95% CI, 7.1%-12.5%) and 5.2% (95% CI, 1.9%-8.4%), respectively. CONCLUSIONS: Our study of angiographic and clinical outcomes for patients with wide-neck aneurysms demonstrates that endovascular coiling with or without stent-assisted coiling is safe, with low rates of perioperative morbidity and mortality. Initial and long-term angiographic outcomes were generally satisfactory, but not ideal. These data provide some baseline comparisons against which emergent technologies can be assessed. PMID- 27256852 TI - A Direct Aspiration, First Pass Technique (ADAPT) versus Stent Retrievers for Acute Stroke Therapy: An Observational Comparative Study. AB - BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers is now the standard therapy for selected patients with ischemic stroke. The technique of A Direct Aspiration, First Pass Technique for the Endovascular Treatment of Stroke (ADAPT) appears promising with a high rate of recanalization. We compared ADAPT versus stent retrievers (the Solitaire device) for efficacy and safety as a front line endovascular procedure. MATERIALS AND METHODS: We analyzed 243 consecutive patients with large intracranial artery occlusions of the anterior circulation, treated within 6 hours with mechanical thrombectomy by either ADAPT or the Solitaire stent. Th primary outcome was complete recanalization (modified TICI >= 2b); secondary outcomes included complication rates and procedural and clinical outcomes. RESULTS: From November 2012 to June 2014, 119 patients were treated with stent retriever (Solitaire FR) and 124 by using the ADAPT with Penumbra reperfusion catheters. The median baseline NIHSS score was the same for both groups (Solitaire, 17 [interquartile range, 11-21] versus ADAPT, 17 [interquartile range, 12-21]). Time from groin puncture to recanalization (Solitaire, 50 minutes [range, 25-80 minutes] versus ADAPT, 45 minutes [range, 27 70 minutes], P = .42) did not differ significantly. However, compared with the Solitaire group, patients treated with ADAPT achieved higher final recanalization rates (82.3% versus 68.9%; adjusted relative risk, 1.18; 95% CI, 1.02-1.37; P = .022), though differences in clinical outcomes between the cohorts were not significant. Use of an adjunctive device was more frequent in the ADAPT group (45.2% versus 13.5%, P < .0001). The rate of embolization in new territories or symptomatic hemorrhage did not differ significantly between the 2 groups. CONCLUSIONS: Front-line ADAPT achieved higher recanalization rates than the Solitaire device. Further randomized controlled trials are warranted to define the best strategy for mechanical thrombectomy. PMID- 27256851 TI - Differentiation of Low- and High-Grade Gliomas Using High b-Value Diffusion Imaging with a Non-Gaussian Diffusion Model. AB - BACKGROUND AND PURPOSE: Imaging-based tumor grading is highly desirable but faces challenges in sensitivity, specificity, and diagnostic accuracy. A recently proposed diffusion imaging method by using a fractional order calculus model offers a set of new parameters to probe not only the diffusion process itself but also intravoxel tissue structures, providing new opportunities for noninvasive tumor grading. This study aimed to demonstrate the feasibility of using the fractional order calculus model to differentiate low- from high-grade gliomas in adult patients and illustrate its improved performance over a conventional diffusion imaging method using ADC (or D). MATERIALS AND METHODS: Fifty-four adult patients (18-70 years of age) with histology-proved gliomas were enrolled and divided into low-grade (n = 24) and high-grade (n = 30) groups. Multi-b-value diffusion MR imaging was performed with 17 b-values (0-4000 s/mm(2)) and was analyzed by using a fractional order calculus model. Mean values and SDs of 3 fractional order calculus parameters (D, beta, and MU) were calculated from the normal contralateral thalamus (as a control) and the tumors, respectively. On the basis of these values, the low- and high-grade glioma groups were compared by using a Mann-Whitney U test. Receiver operating characteristic analysis was performed to assess the performance of individual parameters and the combination of multiple parameters for low- versus high-grade differentiation. RESULTS: Each of the 3 fractional order calculus parameters exhibited a statistically higher value (P <= .011) in the low-grade than in the high-grade gliomas, whereas there was no difference in the normal contralateral thalamus (P >= .706). The receiver operating characteristic analysis showed that beta (area under the curve = 0.853) produced a higher area under the curve than D (0.781) or MU (0.703) and offered a sensitivity of 87.5%, specificity of 76.7%, and diagnostic accuracy of 82.1%. CONCLUSIONS: The study demonstrated the feasibility of using a non-Gaussian fractional order calculus diffusion model to differentiate low- and high-grade gliomas. While all 3 fractional order calculus parameters showed statistically significant differences between the 2 groups, beta exhibited a better performance than the other 2 parameters, including ADC (or D). PMID- 27256853 TI - Prevalence of Intracranial Aneurysms in Patients with Aortic Aneurysms. AB - BACKGROUND AND PURPOSE: Previous studies have suggested an association between aortic aneurysms and intracranial aneurysms with a higher prevalence of intracranial aneurysms in patients with aortic aneurysms. The aims of the present study were to evaluate the incidence of intracranial aneurysms in a large cohort of patients with aortic aneurysms and to identify potential risk factors for intracranial aneurysms in this population. MATERIALS AND METHODS: We included all patients with aortic aneurysms (either abdominal and/or thoracic) who had available cerebral arterial imaging and were seen at our institution during a 15 year period. We identified patients with intracranial aneurysms. Patient demographics, comorbidities, and aortic aneurysm and intracranial aneurysm sizes and locations were analyzed. Univariate analysis was performed with a chi(2) test for categoric variables and a Student t test or ANOVA for continuous variables. RESULTS: A total of 1081 patients with aortic aneurysms were included. Of them, 440 (40.7%) had abdominal aortic aneurysms, 446 (41.3%) had thoracic aortic aneurysms, and 195 (18.0%) had both abdominal aortic and thoracic aortic aneurysms. The overall prevalence of associated intracranial aneurysms in patients with aortic aneurysms was 11.8% (128/1081), with 12.7% (56/440), 10.8% (48/446), and 12.3% (24/195), respectively, in patients with abdominal aortic aneurysms, thoracic aortic aneurysms, and both thoracic aortic aneurysms and abdominal aortic aneurysms. Female patients had a higher risk of associated intracranial aneurysms (OR = 2.08; 95% CI, 1.49-3.03; P = .0002). There was a slight association between abdominal aortic aneurysm size and the prevalence of intracranial aneurysms (OR = 1.02; 95% CI, 1.01-1.03; P = .045). There was no significant association between the locations of the aortic and intracranial aneurysms (P = .93). CONCLUSIONS: The prevalence of intracranial aneurysms is high in patients with aortic aneurysms. Further studies examining the role and cost-effectiveness of intracranial aneurysm screening in patients are warranted. PMID- 27256854 TI - Blood-Labyrinth Barrier Permeability in Meniere Disease and Idiopathic Sudden Sensorineural Hearing Loss: Findings on Delayed Postcontrast 3D-FLAIR MRI. AB - BACKGROUND AND PURPOSE: Meniere disease and idiopathic sudden sensorineural hearing loss can have overlapping clinical presentation and may have similar pathophysiology. Prior studies using postcontrast 3D-FLAIR MR imaging suggest abnormal blood-labyrinth barrier permeability in both conditions, but the 2 diseases have not been directly compared by using the same imaging techniques. We hypothesized that delayed postcontrast 3D-FLAIR MR imaging would show differences in blood-labyrinth barrier permeability between Meniere disease and idiopathic sudden sensorineural hearing loss. MATERIALS AND METHODS: Patients with unilateral Meniere disease (n = 32) and unilateral idiopathic sudden sensorineural hearing loss (n = 11) imaged with delayed postcontrast 3D-FLAIR MR imaging were retrospectively studied. Signal intensities of the medulla and perilymph of the cochlear basal turns of both ears in each patient were measured in a blinded fashion. Cochlea/medulla ratios were calculated for each ear as a surrogate for blood-labyrinth barrier permeability. The ears were segregated by clinical diagnosis. RESULTS: Cochlea/medulla ratio was higher in symptomatic ears of patients with Meniere disease (12.6 +/- 7.4) than in patients with idiopathic sudden sensorineural hearing loss (5.7 +/- 2.0) and asymptomatic ears of patients with Meniere disease (8.0 +/- 3.1), indicating increased blood-labyrinth barrier permeability in Meniere disease ears. The differences in cochlea/medulla ratio between symptomatic and asymptomatic ears were significantly higher in Meniere disease than in idiopathic sudden sensorineural hearing loss. Asymptomatic ears in patients with Meniere disease showed higher cochlea/medulla ratio than symptomatic and asymptomatic ears in patients with idiopathic sudden sensorineural hearing loss. CONCLUSIONS: Increased cochlea/medulla ratio indicates increased blood-labyrinth barrier permeability in Meniere disease compared with idiopathic sudden sensorineural hearing loss. Increased cochlea/medulla ratio in asymptomatic ears of patients with Meniere disease also suggests an underlying systemic cause of Meniere disease and may provide a pathophysiologic biomarker. PMID- 27256855 TI - Probabilistic Fiber-Tracking Reveals Degeneration of the Contralateral Auditory Pathway in Patients with Vestibular Schwannoma. AB - BACKGROUND AND PURPOSE: Vestibular schwannomas cause progressive hearing loss by direct damage to the vestibulocochlear nerve. The cerebral mechanisms of degeneration or plasticity are not well-understood. Therefore, the goal of our study was to show the feasibility of probabilistic fiber-tracking of the auditory pathway in patients with vestibular schwannomas and to compare the ipsi- and contralateral volume and integrity, to test differences between the hemispheres. MATERIALS AND METHODS: Fifteen patients with vestibular schwannomas were investigated before surgery. Diffusion-weighted imaging (25 directions) was performed on a 3T MR imaging system. Probabilistic tractography was performed for 3 partial sections of the auditory pathway. Volume and fractional anisotropy were determined and compared ipsilaterally and contralaterally. The laterality ratio was correlated with the level of hearing loss. RESULTS: Anatomically reasonable tracts were depicted in all patients for the acoustic radiation. Volume was significantly decreased on the hemisphere contralateral to the tumor side for the acoustic radiation and diencephalic section, while fractional anisotropy did not differ significantly. Tracking did not yield meaningful tracts in 3 patients for the thalamocortical section and in 5 patients for the diencephalic section. No statistically significant correlations between the laterality quotient and classification of hearing loss were found. CONCLUSIONS: For the first time, this study showed that different sections of the auditory pathway between the inferior colliculus and the auditory cortex can be visualized by using probabilistic tractography. A significant volume decrease of the auditory pathway on the contralateral hemisphere was observed and may be explained by transsynaptic degeneration of the crossing auditory pathway. PMID- 27256856 TI - Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation. AB - BACKGROUND AND PURPOSE: Quantitative susceptibility mapping and R2* are sensitive to myelin and iron changes in multiple sclerosis lesions. This study was designed to characterize lesion changes on quantitative susceptibility mapping and R2* at various gadolinium-enhancement stages. MATERIALS AND METHODS: This study included 64 patients with MS with different enhancing patterns in white matter lesions: nodular, shell-like, nonenhancing < 1 year old, and nonenhancing 1-3 years old. These represent acute, late acute, early chronic, and late chronic lesions, respectively. Susceptibility values measured on quantitative susceptibility mapping and R2* values were compared among the 4 lesion types. Their differences were assessed with a generalized estimating equation, controlling for Expanded Disability Status Scale score, age, and disease duration. RESULTS: We analyzed 203 lesions: 80 were nodular-enhancing, of which 77 (96.2%) were isointense on quantitative susceptibility mapping; 33 were shell-enhancing, of which 30 (90.9%) were hyperintense on quantitative susceptibility mapping; and 49 were nonenhancing lesions < 1 year old and 41 were nonenhancing lesions 1-3 years old, all of which were hyperintense on quantitative susceptibility mapping. Their relative susceptibility/R2* values were 0.5 +/- 4.4 parts per billion/-5.6 +/- 2.9 Hz, 10.2 +/- 5.4 parts per billion/-8.0 +/- 2.6 Hz, 20.2 +/- 7.8 parts per billion/-3.1 +/- 2.3 Hz, and 33.2 +/- 8.2 parts per billion/-2.0 +/- 2.6 Hz, respectively, and were significantly different (P < .005). CONCLUSIONS: Early active MS lesions with nodular enhancement show R2* decrease but no quantitative susceptibility mapping change, reflecting myelin breakdown; late active lesions with peripheral enhancement show R2* decrease and quantitative susceptibility mapping increase in the lesion center, reflecting further degradation and removal of myelin debris; and early or late chronic nonenhancing lesions show both quantitative susceptibility mapping and R2* increase, reflecting iron accumulation. PMID- 27256857 TI - Safety assessment of a natural tomato oleoresin containing high amounts of Z isomers of lycopene prepared with supercritical carbon dioxide. AB - BACKGROUND: Z-isomers of lycopene, which are abundantly present in processed tomato products, are more bioavailable than (all-E)-lycopene found predominantly in raw tomatoes. Despite extensive studies on the bioavailability and biological activities of Z-isomers of lycopene, detailed studies on their safety and toxicology are limited. RESULTS: The geno-, acute and subacute toxicities of tomato oleoresin that contained high amounts of lycopene Z-isomers (10.9% lycopene with 66.3% Z-isomer content) and had been prepared with supercritical carbon dioxide were investigated. The oleoresin was non-mutagenic in the Ames test with and without metabolic activation (S9 mix). The medial lethal dose (LD50 ) of the oleoresin in rats, as determined by a single-dose oral test, was more than 5000 mg kg body weight-1 (bw) [361 mg (Z)-lycopene kg bw-1 ]. In the 4-week repeated-dose oral toxicity test, rats were administered oleoresin at 4500 mg kg 1 day-1 [325 mg (Z)-lycopene kg bw-1 day-1 ]. There were no clinically significant changes with respect to vital signs, physical examination outcomes and laboratory test values during the test period. CONCLUSION: Based on our findings and as supported by its long history of consumption, tomato oleoresin that contains high amounts of Z-isomers of lycopene prepared with supercritical carbon dioxide can be considered as safe for human consumption. (c) 2016 Society of Chemical Industry. PMID- 27256858 TI - Building professional competence in dental hygiene students through a community based practicum. AB - OBJECTIVES: As Canadians age, there is an increased need for oral health professionals specializing in services for this unique population. Dental hygiene students require exposure to this population to develop professional competencies. This study investigated the dimensions of professional competence that were developed through a practicum for dental hygiene students in long-term care settings while working with older adults. METHODS: Nine dental hygiene students were recruited across two cohorts. All students completed reflective journals describing their practicum experiences. Five students also participated in an audio-recorded focus group and completed a pre-focus group questionnaire. Additionally, the practicum course coordinator completed an audio-recorded interview. Transcripts and journals were coded using a constant comparative approach and themes were identified. RESULTS: Students described developing client-focused skills, such as effective verbal and non-verbal communication with older adults with dementia. Context-based learning was also a large part of the competency development for the practicum students. Understanding the care environment within which these residents lived helped students to understand and empathize why oral health may not be prioritized. Students also developed an understanding of the work of other health professionals in the settings and improved their abilities to communicate with other healthcare providers. However, students recognized that the utility of those interprofessional skills in private practice may be limited. CONCLUSION: Dental hygiene students developed personal and ethical competencies during practicum that are highly transferrable across professional settings. Exposure of students to older adult populations in long term care may increase the likelihood of dental hygienists working in this area. PMID- 27256859 TI - The 2013 cholesterol guideline controversy: Would better evidence prevent pharmaceuticalization? AB - Cardiovascular disease (CVD) remains the leading cause of death globally. A class of medications, known as statins, lowers low-density lipoprotein cholesterol levels, which are associated with CVD. The newest 2013 U.S. cholesterol guideline contains an assessment of risk that greatly expands the number of individuals without CVD for whom statins are recommended. Other countries are also moving in this direction. This article examines the controversy surrounding these guidelines using the 2013 cholesterol guidelines as a case study of broader trends in clinical guidelines to use a narrow evidence base, expand the boundaries of disease and overemphasize pharmaceutical treatment. We find that the recommendation in the 2013 cholesterol guidelines to initiate statins in individuals with a lower risk of CVD is controversial and there is much disagreement on whether there is evidence for the guideline change. We note that, in general, clinical guidelines may use evidence that has a number of biases, are subject to conflicts of interest at multiple levels, and often do not include unpublished research. Further, guidelines may contribute to the "medicalization" or "pharmaceuticalization" of healthcare. Specific policy recommendations to improve clinical guidelines are indicated: these include improving the evidence base, establishing a public registry of all results, including unpublished ones, and freeing the research process from pharmaceutical sector control. PMID- 27256860 TI - Effectiveness and tolerability of liraglutide in patients with type 2 diabetes mellitus and obesity after bariatric surgery. AB - BACKGROUND: Current guidelines do not offer detailed recommendations on antidiabetic drug therapy in type 2 diabetes (T2D) after bariatric surgery (BS), and reported experience is scarce. OBJECTIVES: To evaluate the effectiveness and tolerability of liraglutide at 2 years in patients with morbid obesity after undergoing BS and subsequent relapse, persistence, or new diagnosis of T2D, comparing the results with a cohort of nonsurgical diabetic patients also treated with liraglutide. SETTING: Obesity clinic at a University Hospital. METHODS: We conducted a retrospective study of 2 cohorts of patients (with and without previous BS) with T2D and obesity who had started treatment with liraglutide at least 2 years before their inclusion in the study. The main outcome measures were the differences in glycated hemoglobin (A1C) and weight at 104 weeks between both groups. RESULTS: A total of 164 patients were included, 15 with previous BS and 149 without BS. Mean baseline parameters were A1C 6.6% and body mass index 40.3 kg/m2 for the BS group, and A1C 7.5% and body mass index 39.7 kg/m2 for the non BS group. At 2 years, A1C and weight were significantly decreased in both groups (BS group: DeltaA1C -0.39%, Deltaweight -3.4 kg; non-BS group: DeltaA1C -0.67%, Deltaweight -3.8 kg; all results P<.05), with no significant differences in A1C and weight reduction between both groups. There was a significant lower frequency of withdrawals due to all causes and a nonsignificant lower rate of vomiting and hypoglycemia in patients with BS. CONCLUSIONS: Liraglutide achieved a significant reduction in weight and A1C at 2 years in patients with T2D previously treated with BS, showing good gastrointestinal tolerance. PMID- 27256861 TI - Reversal to normal anatomy after failed gastric bypass: systematic review of indications, techniques, and outcomes. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is one of the most common and most effective procedures performed to combat obesity and obesity-related metabolic disease. In a small proportion of patients, however, complications may necessitate the attempted reversal of RYGB to normal anatomy. The indications for this procedure, as well as technique, complication rate, and success in resolving symptoms are not clearly defined. OBJECTIVE: To assess current literature describing outcomes after reversal of RYGB. METHODS: A systematic search of online databases was conducted. Two independent researchers identified and extracted data for studies describing outcomes after RYGB reversal surgery. Indications, techniques, and outcomes were compared, with results pooled where possible. RESULTS: Eight articles were included in the final data synthesis, incorporating data for 46 patients. Reversal was undertaken due to metabolic, physical, nutritional, or other complications. All successfully underwent RYGB reversal with no reported mortality. Surgical technique varied greatly across the included studies. Postoperative morbidity was high, with 42% suffering complications (56% of which were major). Symptom relief or improvement was achieved in 82% of cases. CONCLUSION: Reversal of RYGB may be undertaken for a variety of indications after RYGB. Though this may successfully eliminate or improve symptoms in a large proportion of patients, the risk of morbidity is high. Surgery should be undertaken after careful patient selection and in appropriately skilled centers only. PMID- 27256862 TI - Treatment of Hypohepatia After Transplantation of Liver From a Living Donor Liver by Transcatheter Embolization, Using a Simulated 3-Dimensional Printing Vascular Model. PMID- 27256863 TI - Acute Right Upper Abdominal Pain With No Trauma History. PMID- 27256864 TI - Multiple Giant Mushroom-like Tumors Inside the Stomach. PMID- 27256866 TI - Left Ventricular Assist Device Implantation With Outflow Graft Tunneling Through the Transverse Sinus. PMID- 27256865 TI - Subunit-Specific Labeling of Ubiquitin Chains by Using Sortase: Insights into the Selectivity of Deubiquitinases. AB - Information embedded in different ubiquitin chains is transduced by proteins with ubiquitin-binding domains (UBDs) and erased by a set of hydrolytic enzymes referred to as deubiquitinases (DUBs). Understanding the selectivity of UBDs and DUBs is necessary for decoding the functions of different ubiquitin chains. Critical to these efforts is the access to chemically defined ubiquitin chains bearing site-specific fluorescent labels. One approach toward constructing such molecules involves peptide ligation by sortase (SrtA), a bacterial transpeptidase responsible for covalently attaching cell surface proteins to the cell wall. Here, we demonstrate the utility of SrtA in modifying individual subunits of ubiquitin chains. Using ubiquitin derivatives in which an N-terminal glycine is unveiled after protease-mediated digestion, we synthesized ubiquitin dimers, trimers, and tetramers with different isopeptide linkages. SrtA was then used in combination with fluorescent depsipeptide substrates to effect the modification of each subunit in a chain. By constructing branched ubiquitin chains with individual subunits tagged with a fluorophore, we provide evidence that the ubiquitin-specific protease USP15 prefers ubiquitin trimers but has little preference for a particular isopeptide linkage. Our results emphasize the importance of subunit-specific labeling of ubiquitin chains when studying how DUBs process these chains. PMID- 27256867 TI - Communications. PMID- 27256869 TI - Prediction of margin involvement and local recurrence after skin-sparing and simple mastectomy. AB - Skin-sparing mastectomy (SSM) facilitates immediate breast reconstruction. We investigated locoregional recurrence rates after SSM compared with simple mastectomy and the factors predicting oncological failure. METHODS: Patients with early breast cancer that underwent mastectomy between 2000 and 2005 at a single institution were studied to ascertain local and systemic recurrence rates between groups. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival. RESULTS: Patients (n = 577) underwent simple mastectomy (80%) or SSM (20%). Median follow up was 80 months. Patients undergoing SSM were of younger average age, less often had involved lymph nodes (22% vs 44%, p < 0.001), more often had DCIS present (79% vs 53%, p < 0.001) and involved margins (29% vs 15%, p = 0.001). Involved surgical margins were associated with large size (p = 0.001). The 8-year local recurrence (LR) rates were 7.9% for SSM and 5% for simple mastectomy respectively (p = 0.35). Predictors of locoregional recurrence were lymph node involvement (HR 8.0, for >4 nodes, p < 0.001) and involved surgical margins (HR 3.3, p = 0.002). In node negative patients, SSM was a predictor of locoregional recurrence (HR 4.8 [1.1, 19.9], p = 0.033). CONCLUSION(S): Delayed reconstruction is more appropriate for node positive early breast cancer after post-mastectomy radiotherapy. Re-excision of involved margins is essential to prevent local recurrence after mastectomy. PMID- 27256868 TI - A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome. AB - Using targeted next generation sequencing, we have identified a splicing mutation (c.526-9_526-5del) in the SLC9A6 gene in a 9-year-old boy with mild intellectual disability (ID), microcephaly, and social interaction disabilities. This intronic microdeletion leads to the skipping of exon 3 and to an in-frame deletion of 26 amino acids in the TM4 domain. It segregates with cognitive impairment or learning difficulties in other members of the family. Mutations in SLC9A6 have been reported in X-linked Christianson syndrome associating severe to profound intellectual deficiency and an Angelman-like phenotype with microcephaly, absent speech, ataxia with progressive cerebellar atrophy, ophthalmoplegia, epilepsy, and neurological regression. The proband and his maternal uncle both have an attenuated phenotype with mild ID, attention deficit disorder, speech difficulties, and mild asymptomatic cerebellar atrophy. The proband also have microcephaly. The mutation cosegregated with learning disabilities and speech difficulties in the female carriers (mother and three sisters of the proband). Detailed neuropsychological, speech, and occupational therapy investigations in the female carriers revealed impaired oral and written language acquisition, with dissociation between verbal and performance IQ. An abnormal phenotype, ranging from learning disability with predominant speech difficulties to mild intellectual deficiency, has been described previously in a large proportion of female carriers. Besides broadening the clinical spectrum of SLC9A6 gene mutations, we present an example of a monogenic origin of mild learning disability. (c) 2016 Wiley Periodicals, Inc. PMID- 27256870 TI - Effect of toluene on Pseudomonas stutzeri ST-9 morphology - plasmolysis, cell size, and formation of outer membrane vesicles. AB - Isolated toluene-degrading Pseudomonas stutzeri ST-9 bacteria were grown in a minimal medium containing toluene (100 mg.L(-1)) (MMT) or glucose (MMG) as the sole carbon source, with specific growth rates of 0.019 h(-1) and 0.042 h(-1), respectively. Scanning (SEM) as well as transmission (TEM) electron microscope analyses showed that the bacterial cells grown to mid-log phase in the presence of toluene possess a plasmolysis space. TEM analysis revealed that bacterial cells that were grown in MMT were surrounded by an additional "material" with small vesicles in between. Membrane integrity was analyzed by leakage of 260 nm absorbing material and demonstrated only 7% and 8% leakage from cultures grown in MMT compared with MMG. X-ray microanalysis showed a 4.3-fold increase in Mg and a 3-fold increase in P in cells grown in MMT compared with cells grown in MMG. Fluorescence-activated cell sorting (FACS) analysis indicated that the permeability of the membrane to propidium iodide was 12.6% and 19.6% when the cultures were grown in MMG and MMT, respectively. The bacterial cell length increased by 8.5% +/- 0.1% and 17% +/- 2%, as measured using SEM images and FACS analysis, respectively. The results obtained in this research show that the presence of toluene led to morphology changes, such as plasmolysis, cell size, and formation of outer membrane vesicles. However, it does not cause significant damage to membrane integrity. PMID- 27256871 TI - Enol ethers as carbonyl surrogates in a modification of the Povarov synthesis of 3-aryl quinolines and their anti-Toxoplasma activity. AB - A novel method for the preparation of 2-carboxyl-3-aryl quinoline derivatives from anilines, ethyl glyoxalate and enol ethers as phenylacetaldehyde surrogates is reported. The three-component coupling reaction occurs rapidly under mild conditions in dichloromethane catalysed by TFA. The method allows a more direct access to 3-aryl quinolines, sidestepping issues encountered with phenylacetaldehyde derivatives. This chemistry was used to prepare quinolines with 3-diarylether functionality that showed low micromolar efficacy (IC50 range: 5-26 MUM) against in vitro Toxoplasma gondii coupled with little or no cytotoxicity (TD50>= 320 MUM) towards the host cells. PMID- 27256872 TI - Value-Based Care in Lung Cancer. PMID- 27256873 TI - Patient Counseling and Management of Symptoms During Olaparib Therapy for Recurrent Ovarian Cancer. AB - : Our primary objective is to review the safety and tolerability profile of olaparib, a novel anticancer therapy, and to discuss key considerations for symptom management in patients with advanced ovarian cancer. Olaparib is the first of a new class of anticancer therapies, poly (ADP-ribose) polymerase (PARP) inhibitors that target tumors that have deficits in homologous recombination repair (such as BRCA mutations) by a process known as synthetic lethality. Through this process, neither the deficiency in homologous recombination repair nor PARP inhibition alone is cytotoxic, but the combination of these two conditions leads to cell death. In December 2014, olaparib received accelerated approval by the U.S. Food and Drug Administration (FDA) as monotherapy for patients with known or suspected deleterious germline BRCA-mutated (as detected by an FDA-approved test) advanced ovarian cancer who had been treated with at least three lines of chemotherapy. Most adverse events (AEs) reported during olaparib clinical trials conducted in patients with recurrent ovarian cancer and measurable disease were of grade 2 or less severity according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. Fatigue and gastrointestinal AEs are among the most common in ovarian cancer clinical trials and can be particularly bothersome to patients. We focus on interventions to address these AEs in patients who are candidates for treatment with olaparib and allow them to remain on therapy for as long as clinically indicated. IMPLICATIONS FOR PRACTICE: Olaparib therapy represents a new approach to treating recurrent ovarian cancer. Some associated adverse events can have a substantial effect on quality of life. It is therefore important for patients, caregivers, and health care providers to have realistic expectations and a thorough understanding of the safety and tolerability profile of olaparib to prevent or alleviate key symptoms so that therapy can continue uninterrupted if possible. This report summarizes a practical approach to supportive care for patients receiving olaparib therapy. PMID- 27256874 TI - Phase I Study of Lenalidomide and Sorafenib in Patients With Advanced Hepatocellular Carcinoma. AB - LESSONS LEARNED: Combination therapies in patients with hepatocellular carcinoma can be associated with overlapping toxicity and are therefore poorly tolerated.Using sorafenib at the maximum tolerated dose can lead to a higher incidence of toxicities. Consequently, combination studies might evaluate sorafenib at alternative schedules or doses to improve tolerance, recognizing this could affect sorafenib efficacy.Although this combination was poorly tolerated, it does not exclude further evaluation of new-generation immunomodulator drugs or immune checkpoint inhibitors in the hope of optimizing tolerance and safety. BACKGROUND: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC), and to date, no combination therapy has demonstrated superior survival compared with sorafenib alone. The immunosuppressive microenvironment in HCC is a negative predictor for survival. Lenalidomide is an immunomodulator and antiangiogenic agent, with limited single agent efficacy in HCC. Based on these data, we designed a phase I study of sorafenib plus lenalidomide to determine the safety and preliminary antitumor activity of this combination. METHODS: This was an open-label, phase I study with a 3+3 dose escalation/de-escalation design. The starting dose of sorafenib was 400 mg p.o. b.i.d. and of lenalidomide was 15 mg p.o. daily with a planned dose escalation by 5 mg per cohort up to 25 mg daily. Dose de-escalation was planned to a sorafenib dose of 400 mg p.o. daily combined with two doses of lenalidomide: 10 mg p.o. daily for a 28-day cycle (cohort 1) and 10 mg p.o. daily for a 21- or 28-day cycle (cohort 2). Patients with cirrhosis, a Child-Pugh score of A-B7, and no previous systemic therapy were eligible. RESULTS: Five patients were enrolled. Their median age was 56 years (range 39-61), and the ECOG status was 0-2. Four patients were treated at dose level (DL) 1. Because of the poor tolerance to the combination associated with grade 2 toxicities, one more patient was treated at DL -1. No dose-limiting toxicity was observed as specified per protocol. The most common toxicities were nausea, anorexia, pruritus, elevated liver enzymes, and elevated bilirubin. Three patients experienced one or more of the following grade 3 toxicities: fatigue (DL 1), increased bilirubin (DL 1), skin desquamation (DL 1), and elevated transaminase levels (DL 1). The median duration of therapy was 1 cycle (range 1-3). All patients discontinued the study, 4 because of progressive disease and 1 by patient preference. The best confirmed response was progressive disease. The median progression-free survival was 1.0 month (95% confidence interval 0.9-2.8), and the median overall survival was 5.9 months (95% confidence interval 3.68-23.4). CONCLUSION: In our small study, the combination of lenalidomide and sorafenib was poorly tolerated and showed no clinical activity. Although the study was closed early because of toxicity concerns, future studies assessing combinations of sorafenib with new-generation immunomodulator drugs or other immunomodulatory agents, should consider lower starting doses of sorafenib to avoid excessive toxicity. PMID- 27256875 TI - Clinical Implications of the Progression-Free Survival Endpoint for Treatment of Hormone Receptor-Positive Advanced Breast Cancer. AB - : Hormonal therapy for advanced breast cancer (ABC) has evolved significantly since the introduction of tamoxifen more than 40 years ago. The availability of selective antiestrogen therapies has further improved treatment options for women with hormone receptor-positive (HR+) ABC. However, with the development of resistance to hormonal therapies, a new treatment paradigm has emerged based on our understanding of biological pathways involved in HR+ breast cancer and mechanisms of resistance to hormonal therapy. Recent drug development efforts have focused on combining hormonal treatment with agents that target mammalian target of rapamycin serine-threonine kinases and cyclin-dependent kinases. In parallel with the evolution of hormonal and targeted therapies, our understanding of the utility of clinical endpoints has deepened. Progression-free survival (PFS) is a primary endpoint well-understood by clinicians and is increasingly accepted as a surrogate for overall survival (OS) by the U.S. Food and Drug Administration. Yet the perceived clinical benefit of PFS to patients is less well understood. Patients may not grasp the implications of prolonged PFS, highlighting the reality that patient preference in treatment selection encompasses factors that extend beyond drug activity. This presents an opportunity for clinicians to discuss PFS with patients in the context of their treatment plans, clinical outcomes, and quality-of-life measures. The objective of this review is to explore the clinical validity of the PFS and OS endpoints and the clinical relevance of PFS and OS to patients, especially in light of drivers that led to a range of treatment options for patients with HR+ ABC. IMPLICATIONS FOR PRACTICE: Advances in drug development during the past two decades have provided numerous options for treatment of advanced breast cancer that include monotherapy with endocrine modulating agents and dual therapy that combines endocrine therapy with an inhibitor targeting the mammalian target of rapamycin serine-threonine kinase or cyclin-dependent kinase pathways known to be involved with resistance. Clinical trial endpoints for breast cancer have evolved as well. Communication of progression-free survival, overall survival, and other outcomes with patients should incorporate the context of the individual's treatment plan and include discussion of response rate, side effects, and quality of life. PMID- 27256876 TI - Overexpression of the genes PDC1 and ADH1 activates glycerol conversion to ethanol in the thermotolerant yeast Ogataea (Hansenula) polymorpha. AB - Conversion of byproduct from biodiesel production glycerol to high-value compounds is of great importance. Ethanol is considered a promising product of glycerol bioconversion. The methylotrophic thermotolerant yeast Ogataea (Hansenula) polymorpha is of great interest for this purpose as the glycerol byproduct contains methanol and heavy metals as contaminants, and this yeast utilizes methanol and is relatively resistant to heavy metals. Besides, O. polymorpha shows robust growth on glycerol and produces ethanol from various carbon sources. The thermotolerance of this yeast is an additional advantage, allowing increased fermentation temperature to 45-48 degrees C, leading to increased rate of the fermentation process and a fall in the cost of distillation. The wild-type strain of O. polymorpha produces insignificant amounts of ethanol from glycerol (0.8 g/l). Overexpression of PDC1 coding for pyruvate decarboxylase enhanced ethanol production up to 3.1 g/l, whereas simultaneous overexpression of PDC1 and ADH1 (coding for alcohol dehydrogenase) led to further increase in ethanol production from glycerol. Moreover, the increased temperature of fermentation up to 45 degrees C stimulated the production of ethanol from glycerol used as the only carbon source up to 5.0 g/l, which exceeds the data obtained by methylotrophic yeast strains reported so far. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27256877 TI - Enhancer activity-based identification of functional enhancers using zebrafish embryos. AB - Chromatin immunoprecipitation (ChIP) against enhancer-associated marks with massive sequencing is a powerful approach to identify genome-wide distributions of putative enhancers. However, functional in vivo analysis is required to elucidate the activities of predicted enhancers. Using zebrafish embryos, we established a ChIP-Injection method that enables identification of functional enhancers based on their enhancer activities in embryos. Each reporter gene possessing the enhancer-associated genomic region enriched by ChIP was injected into zebrafish embryos to analyze the activity of putative enhancers. By using the ChIP-Injection, we identified 32 distinct putative enhancers that drove specific expression. Additionally, we generated transgenic lines that exhibit distributions of the EGFP signal as was observed in the screening. Furthermore, the expression pattern driven by the identified somite-specific enhancer resembled that of the gene acta2. The results indicate that ChIP-Injection provides an efficient approach for identification of active enhancers in a potentially wide variety of developmental tissues and stages. PMID- 27256878 TI - Methods for Measuring Racial Differences in Hospitals Outcomes Attributable to Disparities in Use of High-Quality Hospital Care. AB - OBJECTIVE: To compare two approaches to measuring racial/ethnic disparities in the use of high-quality hospitals. DATA SOURCES: Simulated data. STUDY DESIGN: Through simulations, we compared the "minority-serving" approach of assessing differences in risk-adjusted outcomes at minority-serving and non-minority serving hospitals with a "fixed-effect" approach that estimated the reduction in adverse outcomes if the distribution of minority and white patients across hospitals was the same. We evaluated each method's ability to detect and measure a disparity in outcomes caused by minority patients receiving care at poor quality hospitals, which we label a "between-hospital" disparity, and to reject it when the disparity in outcomes was caused by factors other than hospital quality. PRINCIPAL FINDINGS: The minority-serving and fixed-effect approaches correctly identified between-hospital disparities in quality when they existed and rejected them when racial differences in outcomes were caused by other disparities; however, the fixed-effect approach has many advantages. It does not require an ad hoc definition of a minority-serving hospital, and it estimated the magnitude of the disparity accurately, while the minority-serving approach underestimated the disparity by 35-46 percent. CONCLUSIONS: Researchers should consider using the fixed-effect approach for measuring disparities in use of high quality hospital care by vulnerable populations. PMID- 27256880 TI - Direct time-domain observation of attosecond final-state lifetimes in photoemission from solids. AB - Attosecond spectroscopic techniques have made it possible to measure differences in transport times for photoelectrons from localized core levels and delocalized valence bands in solids. We report the application of attosecond pulse trains to directly and unambiguously measure the difference in lifetimes between photoelectrons born into free electron-like states and those excited into unoccupied excited states in the band structure of nickel (111). An enormous increase in lifetime of 212 +/- 30 attoseconds occurs when the final state coincides with a short-lived excited state. Moreover, a strong dependence of this lifetime on emission angle is directly related to the final-state band dispersion as a function of electron transverse momentum. This finding underscores the importance of the material band structure in determining photoelectron lifetimes and corresponding electron escape depths. PMID- 27256879 TI - Nanos-mediated repression of hid protects larval sensory neurons after a global switch in sensitivity to apoptotic signals. AB - Dendritic arbor morphology is a key determinant of neuronal function. Once established, dendrite branching patterns must be maintained as the animal develops to ensure receptive field coverage. The translational repressors Nanos (Nos) and Pumilio (Pum) are required to maintain dendrite growth and branching of Drosophila larval class IV dendritic arborization (da) neurons, but their specific regulatory role remains unknown. We show that Nos-Pum-mediated repression of the pro-apoptotic gene head involution defective (hid) is required to maintain a balance of dendritic growth and retraction in class IV da neurons and that upregulation of hid results in decreased branching because of an increase in caspase activity. The temporal requirement for nos correlates with an ecdysone-triggered switch in sensitivity to apoptotic stimuli that occurs during the mid-L3 transition. We find that hid is required during pupariation for caspase-dependent pruning of class IV da neurons and that Nos and Pum delay pruning. Together, these results suggest that Nos and Pum provide a crucial neuroprotective regulatory layer to ensure that neurons behave appropriately in response to developmental cues. PMID- 27256881 TI - GENOME ENGINEERING. The Genome Project-Write. PMID- 27256882 TI - Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation. AB - Poly[adenosine diphosphate (ADP)-ribose] polymerases (PARPs) are a family of enzymes that modulate diverse biological processes through covalent transfer of ADP-ribose from the oxidized form of nicotinamide adenine dinucleotide (NAD(+)) onto substrate proteins. Here we report a robust NAD(+) analog-sensitive approach for PARPs, which allows PARP-specific ADP-ribosylation of substrates that is suitable for subsequent copper-catalyzed azide-alkyne cycloaddition reactions. Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1-mediated ADP ribosylation sites across the genome. We found that PARP-1 ADP-ribosylates and inhibits negative elongation factor (NELF), a protein complex that regulates promoter-proximal pausing by RNA polymerase II (Pol II). Depletion or inhibition of PARP-1 or mutation of the ADP-ribosylation sites on NELF-E promotes Pol II pausing, providing a clear functional link between PARP-1, ADP-ribosylation, and NELF. This analog-sensitive approach should be broadly applicable across the PARP family and has the potential to illuminate the ADP-ribosylated proteome and the molecular mechanisms used by individual PARPs to mediate their responses to cellular signals. PMID- 27256883 TI - C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. AB - The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR associated genes (Cas) adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the class 2 type VI CRISPR-Cas effector C2c2 and demonstrate its RNA-guided ribonuclease function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis shows that C2c2 is guided by a single CRISPR RNA and can be programmed to cleave single-stranded RNA targets carrying complementary protospacers. In bacteria, C2c2 can be programmed to knock down specific mRNAs. Cleavage is mediated by catalytic residues in the two conserved Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains, mutations of which generate catalytically inactive RNA-binding proteins. These results broaden our understanding of CRISPR-Cas systems and suggest that C2c2 can be used to develop new RNA-targeting tools. PMID- 27256885 TI - Erratum. PMID- 27256884 TI - Tissue adaptation of regulatory and intraepithelial CD4+ T cells controls gut inflammation. AB - Foxp3(+) regulatory T cells in peripheral tissues (pT(regs)) are instrumental in limiting inflammatory responses to nonself antigens. Within the intestine, pT(regs) are located primarily in the lamina propria, whereas intraepithelial CD4(+) T cells (CD4(IELs)), which also exhibit anti-inflammatory properties and depend on similar environmental cues, reside in the epithelium. Using intravital microscopy, we show distinct cell dynamics of intestinal T(regs) and CD4(IELs) Upon migration to the epithelium, T(regs) lose Foxp3 and convert to CD4(IELs) in a microbiota-dependent manner, an effect attributed to the loss of the transcription factor ThPOK. Finally, we demonstrate that pT(regs) and CD4(IELs) perform complementary roles in the regulation of intestinal inflammation. These results reveal intratissue specialization of anti-inflammatory T cells shaped by discrete niches of the intestine. PMID- 27256886 TI - "The More I Do, the Better I'll Be": The Treatment Preferences of Type 2 Diabetes Among African American Men. AB - To gain better insight to the preferred methods of managing and treating type 2 diabetes among African American men (AA men). Participants ( n = 19) were AA men aged 35 to 69 years, who were diagnosed with type 2 diabetes. Participants were recruited via community outreach efforts, including barbershops and churches located in predominantly African American communities in Southeast United States. On consent, individual interviews were conducted, audio recorded, and subsequently transcribed. Transcripts were analyzed using a phenomenological approach, and focused on identifying common themes among the descriptions of AA men's experiences specific to type 2 diabetes. Participants' statements indicated three main commonalities regarding treatment preferences which were medication, dietary changes, and increase in exercise. Some participants from the study stated that they preferred taking oral medication primarily out of convenience, lack of pain, and how well the medicine makes them feel. Others stated educating themselves and having a consistent relationship with the diabetes physician has assisted them the most. Other participants shared preferences of being dedicated to proper diet and exercise without any medication (pill or injection), as well as maintaining the mental motivation needed to sustain management. Some participants preferred to not take an oral pill, while some did not mind taking pills at all. For some of the participants, it appears that it is easier for them to manage their diabetes by prescription medication than by lifestyle changes such as diet and exercise. Future studies are needed to investigate how social support system also assists these men in managing their diabetes. PMID- 27256887 TI - Evaluation of the effect of time on the distribution of zinc oxide nanoparticles in tissues of rats and mice: a systematic review. AB - To evaluate the time effect on the distribution of zinc oxide nanoparticles (ZnO NPs) in tissues from rats and mice, a search on the PubMed, Embase, SpringerLink, Scopus, Science Direct, Cochrane, CNKI, Wanfang, and vip databases up to September 2014 was performed, followed by screening, data extraction, and quality assessment. Thirteen studies were included. At 24 h, Zn content was mainly distributed in the liver, kidney, and lung. At >=7 days, Zn content was mainly distributed in the liver, kidney, lung, and brain. ZnO NPs are readily deposited in tissues. Furthermore, as time increases, Zn content decreases in the liver and kidney, but increases in the brain. PMID- 27256888 TI - In situ synthesised TiO2-chitosan-chondroitin 4-sulphate nanocomposites for bone implant applications. AB - The artificial materials for bone implant applications are gaining more importance in the recent years. The series titania-chitosan-chondroitin 4 sulphate nanocomposites of three different concentrations (2:1:x, where x- 0.125, 0.25, 0.5) have been synthesised by in situ sol-gel method and characterised by various techniques. The particle size of the nanocomposites ranges from 30-50 nm. The bioactivity, swelling nature, and the antimicrobial nature of the nanocomposites were investigated. The swelling ability and bioactivity of the composites is significantly greater and they possess high zone of inhibition against the microorganisms such as Staphylococcus aureus and Escherichia coli. The cell viability of the nanocomposites were evaluated by using MG-63 and observed the composites possess high cell viability at low concentration. The excellent bioactivity and biocompatibility makes these nanocomposites a promising biomaterial for bone implant applications. PMID- 27256889 TI - Development of nanoformulation of picroliv isolated from Picrorrhiza kurroa. AB - Picroliv, a mixture of picroside I and kutkoside isolated from rhizome of Picrorrhiza kurroa has been reported for many pharmaceutical properties such as hepatoprotective, anticholestatic, antioxidant and immune-modulating activity. However, picroliv possessed lesser efficacy due to its poor aqueous solubility and lesser bioavailability. To find solution, picroliv was loaded into biodegradable poly lactic acid nanoparticles (PLA NPs) using solvent evaporation method. The picroliv-loaded PLA NPs were characterised by UV-vis spectroscopy, atomic force microscopy, transmission electron microscopy, Fourier transform infrared and Zeta sizer. The size of picroliv-loaded PLA NPs was 182 +/- 20 nm. Zeta potential of picroliv-loaded PLA NPs was -23.5 mV, indicated their good stability. In vitro picroliv release from picroliv-loaded PLA NPs showed an initial burst release followed by slow and sustained release. The efficacy of picroliv-loaded PLA NPs was assessed against KB cell lines. Blank PLA NPs showed no cytotoxicity on KB cells. The picroliv-loaded PLA NPs showed more cytotoxic activity on KB cells as compared to the pure drug. Hence, the developed picroliv nanoformulation would find potential application in pharma-sector. PMID- 27256890 TI - Template free synthesis of natural carbohydrates functionalised fluorescent silver nanoclusters. AB - Template-assisted synthesis is one of the most recognised techniques for fabrication of silver nanoclusters (AgNCs). However, this process is time consuming, toxic and expensive. In this study, the authors report a completely novel approach for the green and facile synthesis of AgNCs using Matricaria chamomilla, without any additional template. Fluorescent and colloidally stable AgNCs with average particle size of 2.4 nm were successfully produced. They found that carbohydrates from Matricaria chamomilla act as an ideal template to generate fluorescent AgNCs. Moreover, oxygen-bearing functional groups were validated to be the active groups for anchoring and reducing of Ag(+) ions. The novel carbohydrate coating method makes the prepared nanoclusters completely hydrophilic and stable in aqueous matrices. PMID- 27256891 TI - Characterisation of optically driven microstructures for manipulating single DNA molecules under a fluorescence microscope. AB - Optical tweezers are powerful tools for manipulating single DNA molecules using fluorescence microscopy, particularly in nanotechnology-based DNA analysis. We previously proposed a manipulation technique using microstructures driven by optical tweezers that allows the handling of single giant DNA molecules of millimetre length that cannot be manipulated by conventional techniques. To further develop this technique, the authors characterised the microstructures quantitatively from the view point of fabrication and efficiency of DNA manipulation under a fluorescence microscope. The success rate and precision of the fabrications were evaluated. The results indicate that the microstructures are obtained in an aqueous solution with a precision ~50 nm at concentrations in the order of 10(6) particles/ml. The visibility of these microstructures under a fluorescence microscope was also characterised, along with the elucidation of the fabrication parameters needed to fine tune visibility. Manipulating yeast chromosomal DNA molecules with the microstructures illustrated the relationship between the efficiency of manipulation and the geometrical shape of the microstructure. This report provides the guidelines for designing microstructures used in single DNA molecule analysis based on on-site DNA manipulation, and is expected to broaden the applications of this technique in the future. PMID- 27256892 TI - Photo-induced Leishmania DNA degradation by silver-doped zinc oxide nanoparticle: an in-vitro approach. AB - Recently, the authors reported newly synthesised polyethylene glycol (PEG)ylated silver (9%)-doped zinc oxide nanoparticle (doped semiconductor nanoparticle (DSN)) which has high potency for killing Leishmania tropica by producing reactive oxygen species on exposure to sunlight. The current report is focused on Leishmania DNA interaction and damage caused by the DSN. Here, we showed that the damage to Leishmania DNA was indirect, as the DSN was unable to interact with the DNA in intact Leishmania cell, indicating the incapability of PEGylated DSN to cross the nucleus barrier. The DNA damage was the result of high production of singlet oxygen on exposure to sunlight. The DNA damage was successfully prevented by singlet oxygen scavenger (sodium azide) confirming involvement of the highly energetic singlet oxygen in the DNA degradation process. PMID- 27256893 TI - Synthesis and characterisation of metal nanoparticles and their effects on seed germination and seedling growth in commercially important Eruca sativa. AB - The synthesis, characterisation and application of metal nanoparticles have become an important and attractive branch of nanotechnology. In current study, metallic nanoparticles of silver, copper, and gold were synthesised using environment friendly method (polyols process), and applied on medicinally important plant: Eruca sativa. Effects of application of these nanoparticles were evaluated on seed germination frequency and biochemical parameters of plant tissues. Seeds of E. sativa were germinated on Murashige and Skoog (MS) medium incorporated with various combinations of nanoparticles suspension (30 ug/ml). Phytotoxicity study showed that nanoparticles could induce stress in plants by manipulating the endogenous mechanisms. In response to these stresses, plants release various defensive compounds; known as antioxidant secondary metabolites. These plants derived secondary metabolites having a great potential in treating the common human ailments. In the authors study, small-sized nanoparticles showed higher toxicity levels and enhanced secondary metabolites production, total protein content, total flavonoids content and total phenolics content. PMID- 27256894 TI - Biogenic green synthesis of monodispersed gum kondagogu (Cochlospermum gossypium) iron nanocomposite material and its application in germination and growth of mung bean (Vigna radiata) as a plant model. AB - An eco-friendly green and one-pot synthesis of highly monodispersed iron (Fe) nanoparticles (NPs) by using a natural biopolymer, gum kondagogu (GK) as reducing and capping agent is proposed. The NPs synthesised were characterised by ultra violet-visible spectroscopy, transmission electron microscopy, scanning electron microscopy and X-ray diffraction. As the concentration of gum and time increases, the intensity of NPs formation increased. The NPs were highly monodispersed with uniform circular shapes of 2-6 nm in size. The formed NPs were crystalline in nature which was confirmed by diffraction analysis. The conversion ratio of Fe ionic form to NPs was 21% which was quantified by inductively coupled plasma mass spectroscopy (ICP-MS). Fe is essential for plant growth and development. A study was conducted to examine the effect of these NPs on the growth of mung bean (Vigna radiata). The radical length and biomass was increased in seeds exposed to Fe NPs than the ions. The uptake of Fe NPs by the sprouts was also quantified by ICP-MS, in which Fe was more in mung bean seeds exposed to NPs. The alpha-amylase activity was increased in the seeds exposed to NPs. The observed increase in the biomass by Fe NPs and seed germination may facilitate its application in the agriculture as an important cost-effective method for plant growth. PMID- 27256895 TI - Effects of nanosilver on sound absorption coefficients in solid wood species. AB - Sound absorption coefficients (ACs) were determined in five solid woods (poplar, beech, walnut, mulberry, and fir) in the longitudinal and tangential directions at four different frequencies of 800, 1000, 2000, and 4000 Hz. The length of the longitudinal and tangential specimens was 50-mm and 10-mm, respectively. Separate sets of specimens were impregnated with either nanosilver suspension or water. The size range of nanoparticles was 30-80 nm. Results showed that sound ACs were lower in longitudinal specimens because sound waves could penetrate the open ends of vessels more easily, being trapped and damped there. Impregnation with both nanosilver suspension and water resulted in a significant decrease in the sound ACs. The decrease in the ACs was due to the collapsing and accumulation of perforation plates and cell parts, blocking the way through which waves could pass through the vessels. This caused higher damping due to a phenomenon called vibration decay. Correlation between gas permeability versus sound AC is significantly dependant on the porous structure of individual specimens. PMID- 27256896 TI - Biofabrication of nanogold from the flower extracts of Lantana camara. AB - The present investigation was done to explore the potential of Lantana camara (L. camara) flower in the fabrication of gold nanoparticles (AuNPs). The shape and size of AuNPs have been successfully controlled by introducing small amounts of L. camara flower extract. It produced spherical nanogold of average size 10.6 +/- 2.9 nm without any aggregation and showed significant photocatalytic degradation activity of the methylene blue (>62%, 10 mg/L) in the presence of solar light. In addition, the experimental approach is inexpensive, rapid and eco-friendly for industrial scale production of nanoparticles. PMID- 27256897 TI - Optimisation of nitrate reductase enzyme activity to synthesise silver nanoparticles. AB - Today, the synthesis of silver nanoparticles (Ag NPs) is very common since it has many applications in different areas. The synthesis of these nanoparticles is done by means of physical, chemical, or biological methods. However, due to its inexpensive and environmentally friendly features, the biological method is more preferable. In the present study, using nitrate reductase enzyme available in the Escherichia coli (E. coli) bacterium, the biosynthesis of Ag NPs was investigated. In addition, the activity of the nitrate reductase enzyme was optimised by changing its cultural conditions, and the effects of silver nitrate (AgNO(3)) concentration and enzyme amount on nanoparticles synthesis were studied. Finally, the produced nanoparticles were studied using ultraviolet visible (UV-Vis) spectrophotometer, dynamic light scattering technique, and transmission electron microscopy. UV-Visible spectrophotometric study showed the characteristic peak for Ag NPs at wavelength 405-420 nm for 1 mM metal precursor solution (AgNO(3)) with 1, 5, 10, and 20 cc supernatant and 435 nm for 0.01M AgNO(3) with 20 cc supernatant. In this study, it was found that there is a direct relationship between the AgNO(3) concentration and the size of produced Ag NPs. PMID- 27256899 TI - Erratum: 'Comparative analysis of biosynthesised and chemosynthesised silver nanoparticles with special reference to their antibacterial activity against pathogens'. PMID- 27256898 TI - Alkaline treatment effect on the properties of in-situ synthesised ZnO nanoparticles on cotton fabric. AB - In this study, an in-situ approach was used to synthesise zinc oxide nanoparticles on the surface of cotton fabric. The effect of alkaline pre- and after-treatment and Zn(2+) concentration was studied on the morphological, structural, thermal, photocatalytic, and antibacterial properties of loaded cotton fabrics. Scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffractometer, thermogravimetric analysis, and attenuated total reflection Fourier transform infrared spectrometer were used to characterise the properties of loaded cotton fabrics. Alkaline after-treatment of cotton fabric presented more dispersed zinc oxide nanoparticles, and an increase in Zn(2+) concentration led to form agglomerated nanoparticles on the surface of cotton fibres. The loaded cotton fabrics with zinc oxide nanoparticles presented an inhibition zone against Staphylococcus aureus and Escherichia coli. In addition, the stain of methylene blue on the surface of loaded samples was degraded after irradiated under visible light. PMID- 27256900 TI - The N-MOmentum trial: Building momentum to advance trial methodology in a rare disease. PMID- 27256901 TI - Resolving Fine-Scale Heterogeneity of Co-seismic Slip and the Relation to Fault Structure. AB - Fault slip distributions provide important insight into the earthquake process. We analyze high-resolution along-strike co-seismic slip profiles of the 1992 Mw = 7.3 Landers and 1999 Mw = 7.1 Hector Mine earthquakes, finding a spatial correlation between fluctuations of the slip distribution and geometrical fault structure. Using a spectral analysis, we demonstrate that the observed variation of co-seismic slip is neither random nor artificial, but self-affine fractal and rougher for Landers. We show that the wavelength and amplitude of slip variability correlates to the spatial distribution of fault geometrical complexity, explaining why Hector Mine has a smoother slip distribution as it occurred on a geometrically simpler fault system. We propose as a physical explanation that fault complexity induces a heterogeneous stress state that in turn controls co-seismic slip. Our observations detail the fundamental relationship between fault structure and earthquake rupture behavior, allowing for modeling of realistic slip profiles for use in seismic hazard assessment and paleoseismology studies. PMID- 27256902 TI - A safe and feasible "clock-face" duct-to-mucosa pancreaticojejunostomy with a very low incidence of anastomotic failure: A single center experience of 248 patients. AB - INTRODUCTION: Postoperative pancreatic fistula (POPF) is one of the most frequent and serious postoperative complications of pancreatoduodenectomy (PD). We sought to assess the impact of a novel pancreaticojejunostomy (PJ) on the rates of POPF and overall postoperative complications. METHODS: Between 01/2010 and 12/2013, a total of 248 consecutive patients who underwent PD with a modified PJ were identified from our database and retrospectively analyzed. POPF cases were divided into three categories (ISGPF-international study group-guidelines): biochemical fistula without clinical sequelae (grade A), fistula requiring any therapeutic intervention (grade B), and fistula with severe clinical sequelae (grade C). Perioperative outcomes were recorded and analyzed. RESULTS: The overwhelming majority of patients had no evidence of fistula. Grade A POPF was observed in 9 (3.62%), grade B in 1 (0.40%), and grade C in 0 patients. There were no postoperative deaths. Overall complications occurred in 61 patients (24.59%) of patients after PD. CONCLUSIONS: This modified pancreaticojejunostomy is widely applicable and is associated with very low rates of POPF, low postoperative morbidity and mortality. Overall, it is a feasible and safe novel approach with excellent short-term outcomes. PMID- 27256903 TI - Management of traumatic small bowel injury by mechanical anastomosis "without resection" during damage control laparotomy. PMID- 27256904 TI - Long-Range Coulomb Effect in Intense Laser-Driven Photoelectron Dynamics. AB - In strong field atomic physics community, long-range Coulomb interaction has for a long time been overlooked and its significant role in intense laser-driven photoelectron dynamics eluded experimental observations. Here we report an experimental investigation of the effect of long-range Coulomb potential on the dynamics of near-zero-momentum photoelectrons produced in photo-ionization process of noble gas atoms in intense midinfrared laser pulses. By exploring the dependence of photoelectron distributions near zero momentum on laser intensity and wavelength, we unambiguously demonstrate that the long-range tail of the Coulomb potential (i.e., up to several hundreds atomic units) plays an important role in determining the photoelectron dynamics after the pulse ends. PMID- 27256905 TI - Defect engineering of the electronic transport through cuprous oxide interlayers. AB - The electronic transport through Au-(Cu2O)n-Au junctions is investigated using first-principles calculations and the nonequilibrium Green's function method. The effect of varying the thickness (i.e., n) is studied as well as that of point defects and anion substitution. For all Cu2O thicknesses the conductance is more enhanced by bulk-like (in contrast to near-interface) defects, with the exception of O vacancies and Cl substitutional defects. A similar transmission behavior results from Cu deficiency and N substitution, as well as from Cl substitution and N interstitials for thick Cu2O junctions. In agreement with recent experimental observations, it is found that N and Cl doping enhances the conductance. A Frenkel defect, i.e., a superposition of an O interstitial and O substitutional defect, leads to a remarkably high conductance. From the analysis of the defect formation energies, Cu vacancies are found to be particularly stable, in agreement with earlier experimental and theoretical work. PMID- 27256906 TI - Investigations at the 'Four-Front' of Mammalian Development. AB - Understanding how and when cells become different during embryogenesis is a goal that is at the forefront of investigations in mammalian development. Two recent studies from the laboratories of Nicholas Plachta and Magdalena Zernicka-Goetz present evidence that cellular heterogeneities detected in four-cell mouse embryos bias the process of cell fate acquisition thereafter. PMID- 27256907 TI - Cardiovascular Nursing: The Future is Bright. PMID- 27256908 TI - Two Cases of Right Atrial Mural Endocarditis Caused by Staphylococcus Aureus. AB - Mural endocarditis is a rare clinical entity with an extremely high mortality rate. It is usually predisposed by an underlying structural intracardiac abnormality. We present two cases of mural endocarditis occurring in the right atrium which were complicated by septic pulmonary embolism, one of which was predisposed by a jet lesion secondary to a coronary artery fistula. Both cases were successfully managed conservatively with excellent long-term outcomes. PMID- 27256909 TI - Extreme environments in the critical zone: Linking acidification hazard of acid sulfate soils in mound spring discharge zones to groundwater evolution and mantle degassing. AB - A decrease in flow from the iconic travertine mound springs of the Great Artesian Basin in South Australia has led to the oxidation of hypersulfidic soils and extreme soil acidification, impacting their unique groundwater dependent ecosystems. The build-up of pyrite in these systems occurred over millennia by the discharge of deep artesian sulfate-containing groundwaters through organic rich subaqueous soils. Rare iron and aluminium hydroxysulfate minerals form thick efflorescences due to high evaporation rates in this arid zone environment, and the oxidised soils pose a significant risk to local aquatic and terrestrial ecosystems. The distribution of extreme acidification hazard is controlled by regional variations in the hydrochemistry of groundwater. Geochemical processes fractionate acidity and alkalinity into separate parts of the discharge zone allowing potentially extreme environments to form locally. Differences in groundwater chemistry in the aquifer along flow pathways towards the spring discharge zone are related to a range of processes including mineral dissolution and redox reactions, which in turn are strongly influenced by degassing of the mantle along deep crustal fractures. There is thus a connection between shallow critical zone ecosystems and deep crustal/mantle processes which ultimately control the formation of hypersulfidic soils and the potential for extreme geochemical environments. PMID- 27256910 TI - New cytotoxic and anti-inflammatory steroids from the soft coral Klyxum flaccidum. AB - Four new steroids, namely klyflaccisteroids G-J (1-4) were isolated from the Formosan soft coral Klyxum flaccidum. The structures of compounds 1-4 were established by spectral data analysis (IR, MS, 1D and 2D NMR) and comparison of spectral data with those of the related known compounds. Cytotoxicity assay revealed that 4 exhibited inhibition activity against the growth of HT-29, P388 and K562 cancer cell lines, whereas 2 showed selective cytotoxicity toward P388 cells. Compound 4 was also found to display significant anti-inflammatory activity for suppressing superoxide anion generation (O2(-)) and elastase release. PMID- 27256911 TI - Synthesis and structure-activity relationship of 2,6-disubstituted pyridine derivatives as inhibitors of beta-amyloid-42 aggregation. AB - It is assumed that amyloid-beta aggregation is a crucial event in the pathogenesis of Alzheimer's disease. Novel 2,6-disubstituted pyridine derivatives were designed to interact with the beta-sheet conformation of Abeta via donor acceptor-donor hydrogen bond formation. A series of pyridine derivatives were synthesized and tested regarding their potential to inhibit the aggregation of Abeta. The 2,6-diaminopyridine moiety was identified as a key component to inhibit Abeta aggregation. Overall, compounds having three 2,6-disubstituted pyridine units separated by at least one C2- or C3-linker displayed the most potent inhibition of Abeta aggregation. PMID- 27256912 TI - Discovery of hydroxyl 1,2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. AB - Hydroxyl 1,2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound 16 which demonstrated robust pharmacodynamic effects in human CETP/apo B100 dual transgenic mice. PMID- 27256913 TI - Discovery of indole inhibitors of chemokine receptor 9 (CCR9). AB - Irritable bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) are serious chronic diseases affecting millions of patients worldwide. Studies of human chemokine biology has suggested C-C chemokine receptor 9 (CCR9) may be a key mediator of pro-inflammatory signaling. Discovery of agents that inhibit CCR9 may lead to new therapies for CD and UC patients. Herein we describe the evolution of a high content screening hit (1) into potent inhibitors of CCR9, such as azaindole 12. PMID- 27256914 TI - Two pairs of farnesyl phenolic enantiomers as natural nitric oxide inhibitors from Ganoderma sinense. AB - Four new farnesyl phenolic compounds, ganosinensols A-D (1-4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Two pairs of enantiomers, 1/2, and 3/4 were isolated by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of 1-4 were assigned by ECD spectra. All of these isolated compounds showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values from 1.15 to 2.26MUM. PMID- 27256916 TI - Gene switching rate determines response to extrinsic perturbations in the self activation transcriptional network motif. AB - Gene switching dynamics is a major source of randomness in genetic networks, also in the case of large concentrations of the transcription factors. In this work, we consider a common network motif - the positive feedback of a transcription factor on its own synthesis - and assess its response to extrinsic noises perturbing gene deactivation in a variety of settings where the network might operate. These settings are representative of distinct cellular types, abundance of transcription factors and ratio between gene switching and protein synthesis rates. By investigating noise-induced transitions among the different network operative states, our results suggest that gene switching rates are key parameters to shape network response to external perturbations, and that such response depends on the particular biological setting, i.e. the characteristic time scales and protein abundance. These results might have implications on our understanding of irreversible transitions for noise-related phenomena such as cellular differentiation. In addition these evidences suggest to adopt the appropriate mathematical model of the network in order to analyze the system consistently to the reference biological setting. PMID- 27256917 TI - Influence of long-term inundation and nutrient addition on denitrification in sandy wetland sediments from Poyang Lake, a large shallow subtropical lake in China. AB - Wetlands at aquatic/terrestrial transition zones may play an important role in nitrogen removal due to the denitrification during inundation events. In this study, air-dried sandy sediment cores from Poyang Lake's wetlands were continuously inundated in the laboratory to investigate the rate, efficiency, and pattern of denitrification at the sediment-water interface (SWI). Denitrification rates responded to inundation in three stages: an adaptive period, a rapid growth period, and a stable period. The average denitrification rates during these stages were 52.62 +/- 11.33 MUmol N2 m-2 h-1, 115.74 +/- 58.40 MUmol N2 m-2 h-1 and 187.74 +/- 16.44 MUmol N2 m-2 h-1, respectively. Multiple regression analysis showed that inundation duration was the most important factor controlling denitrification rates at the SWI rather than nitrate concentrations, which were also positively correlated with denitrification rates. Changes in water content, oxidation-reduction potential (Eh), and pH in the surface sediments, which were consequences of inundation, significantly influenced the denitrification rate (p < 0.05). The N2O/(N2O + N2) flux ratio in denitrification production varied from 1.61% during the adaptive period to 0.03% in the stable period, suggesting that continuous inundation of sediments in aquatic-terrestrial transition zones of Poyang Lake could decrease the proportion of greenhouse gases (N2O). Since inputs of bioavailable nitrogen and phosphorus to Poyang Lake have increased in recent decades, the influence of elevated nutrients on denitrification under continuous inundation were also evaluated by simulation experiments. The results showed that increased nitrate or phosphate loading stimulate denitrification rates in sandy sediments during the inundation process. The addition of nitrate plus phosphate showed a stronger influence on denitrification than single nutrient additions. This study facilitates understanding of the influence of continuous inundation and elevated nutrients on denitrification in sandy sediments in aquatic/terrestrial transition zones. PMID- 27256919 TI - Immunoaffinity chromatography in antivenomics studies: Various parameters that can affect the results. AB - Antivenomics is a recently developed powerful method for the study of antivenom antibody profiles when bound to homologous and heterologous snake venoms. The information obtained is useful in gaining an understanding of venom protein immunogenicity, antivenom potency and also for the improvement of antivenom potency and paraspecificity. The preferred method used in this type of study is immunoaffinity chromatography of the venom proteins on an antivenom IgG (or F(ab')2) column where the bound and unbound proteins can be separated and identified. However, there are some parameters of the immunochromatography that can significantly affect the binding of the proteins to the immunoaffinity matrix and lead to imprecise results in antivenom immunoprofiling. The present study demonstrated that the ligand density (mg IgG/ml of the matrix), the buffers used for binding and washing the venom proteins, the amount of venom loaded, the abundance of some venom protein(s) and the eluting buffers can significantly alter the binding of the proteins to the matrix and consequently the conclusions drawn from antivenomics studies. Furthermore, the immunochromatographic procedure can be extended to include the estimation of the relative affinity of venom protein-antibody interactions that can provide additional information useful to antivenomics study. PMID- 27256918 TI - Mutation of the Traj18 gene segment using TALENs to generate Natural Killer T cell deficient mice. AB - Invariant Natural Killer T (iNKT) cells are a unique subset of T lymphocytes that have been implicated in both promoting and suppressing a multitude of immune responses. In mice, iNKT cells express T cell antigen receptors (TCRs) comprising a unique TCRalpha rearrangement between the Trav11 and Traj18 gene segments. When paired with certain Trbv TCRbeta chains, these TCRs recognize lipid antigens presented by the major histocompatibility complex (MHC) class I-like molecule, CD1d. Until recently, the sole model of iNKT deficiency targeted the Jalpha18, which is absolutely required to form the TCR with the appropriate antigenic specificity. However, these mice were demonstrated to have a large reduction in TCR repertoire diversity, which could confound results arising from studies using these mice. Here, we have created a new NKT-deficient mouse strain using transcription activator-like effector nuclease (TALEN) technology to only disrupt the expression of Jalpha18, leaving the remaining Jalpha repertoire unperturbed. We confirm that these mice lack iNKT cells and do not respond to lipid antigen stimulation while the development of conventional T cells, regulatory T cells, and type Ib NKT cells is normal. This new mouse strain will serve as a new model of iNKT cell deficiency to facilitate our understanding of iNKT biology. PMID- 27256920 TI - Freestanding three-dimensional core-shell nanoarrays for lithium-ion battery anodes. AB - Structural degradation and low conductivity of transition-metal oxides lead to severe capacity fading in lithium-ion batteries. Recent efforts to solve this issue have mainly focused on using nanocomposites or hybrids by integrating nanosized metal oxides with conducting additives. Here we design specific hierarchical structures and demonstrate their use in flexible, large-area anode assemblies. Fabrication of these anodes is achieved via oxidative growth of copper oxide nanowires onto copper substrates followed by radio-frequency sputtering of carbon-nitride films, forming freestanding three-dimensional arrays with core-shell nano-architecture. Cable-like copper oxide/carbon-nitride core shell nanostructures accommodate the volume change during lithiation-delithiation processes, the three-dimensional arrays provide abundant electroactive zones and electron/ion transport paths, and the monolithic sandwich-type configuration without additional binders or conductive agents improves energy/power densities of the whole electrode. PMID- 27256921 TI - Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of 51 Cr-EDTA. AB - We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of 51 Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine <200 MUmol l 1 entered the study. 51 Cr-EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0.25 g kg-1 body weight (150 mg ml-1 ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3.5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brochner Mortensen. Mean plasma clearance (+/-SD) for 51 Cr-EDTA was 59.7 +/- 18.8 ml min 1 . The mean plasma clearance for mannitol ranged between 57.0 +/- 20.1 and 61.1 +/- 16.7 ml min-1 and Vd was 21.3 +/- 6.2% per kg b.w. The between-method bias ranged between -0.23 and 2.73 ml min-1 , the percentage error between 26.7 and 39.5% and the limits of agreement between -14.3/17.2 and -25.3/19.9 ml min-1 . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41 63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and 51 Cr-EDTA for the assessment of GFR. PMID- 27256922 TI - Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man. AB - Orexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism. PMID- 27256923 TI - Combinatorial therapy with three-dimensionally cultured adipose-derived stromal cells and self-assembling peptides to enhance angiogenesis and preserve cardiac function in infarcted hearts. AB - Even though stem cell therapy is a promising angiogenic strategy to treat ischaemic diseases, including myocardial infarction (MI), therapeutic efficacy is limited by low survival and retention of transplanted cells in ischaemic tissues. In addition, therapeutic angiogenesis depends on stimulating host angiogenesis with paracrine factors released by transplanted cells rather than on direct blood vessel formation by transplanted cells. In the present study, to overcome these limitations and to enhance the therapeutic efficacy of MI treatment, combinatorial therapy with three-dimensional cell masses (3DCMs) and self assembling peptides (SAPs) was tested in a rat MI model. Spheroid-type 3DCMs, which are vascular differentiation-induced cells, were prepared by culturing human adipose-derived stromal cells on a fibroblast growth factor-immobilized surface. The SAPs were used as the carrier material to increase engraftment of transplanted cells. After coronary artery ligation, 3DCMs were combined with SAPs and were transplanted into ischaemic lesions. The therapeutic potential was evaluated 4 weeks after treatment. By combining 3DCMs and SAPs, survival and retention of transplanted cells increased threefold when compared with treatment with 3DCMs alone and transplanted cells established vascular networks in infarcted hearts. In addition, the size of the infarct in the 3DCM + SAP group was reduced to 6.09 +/- 2.83% by the promotion of host angiogenesis and cardiac function was preserved, as demonstrated by a 54.25 +/- 4.42% increase in the ejection fraction. This study indicates that combinatorial therapy with 3DCM and SAPs could be a promising strategy for therapeutic angiogenesis to treat MI. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27256925 TI - Regeneration of hair and other skin appendages: A microenvironment-centric view. AB - Advances in skin regeneration have resulted in techniques and products that have allowed regeneration of both the dermis and epidermis. Yet complete skin regeneration requires the adnexal skin structures. Thus it is crucial to understand the regenerative potential of hair follicles where genetic, nutritional, and hormonal influences have important effects and are critical for skin regeneration. The follicular stem cell niche serves as an anatomical compartment, a structural unit, a functional integrator, and a dynamic regulator necessary to sustain internal homeostasis and respond to outside stimuli. In particular, mechanics such as pressure, compression, friction, traction, stretch, shear, and mechanical wounding can influence hair loss or growth. Relevant niche signaling pathways such as Wnt, bone morphogenetic protein, fibroblast growth factor, Shh, and Notch may yield potential targets for therapeutic interventions. PMID- 27256924 TI - Intralymphatic histiocytosis comprises M2 macrophages in superficial dermal lymphatics with or without smooth muscles. AB - Intralymphatic histiocytosis represents a rare reactive disorder, which is characterized by the accumulation of macrophages within lymphatic vessels and observed predominantly in upper extremities. The infiltration and preferential M2 differentiation of macrophage are observed in chronic lymphedema, and lymphedema is considered a causative factor of intralymphatic histiocytosis. However, what causes accumulation of histiocytes in the lymphatic vessels remains unclear, and investigation regarding the characteristics of the macrophages has not been evaluated. We present a case of intralymphatic histiocytosis, in which immunohistochemical staining for both macrophages and lymphatic vessels was performed to evaluate the nature of macrophages within lymphatic vessels and to determine the causative factor. Aggregated macrophages were shown to be M2 macrophages positive for CD68, CD163 and CD206 but negative for inducible nitric oxide synthase. Thick lymphatic vessels positive for D2-40 and alpha-SMA in the superficial dermis were observed. We speculate that chronic lymphedema leads to hypertrophy of lymphatic vessels with smooth muscle in the superficial dermis, which may be a kind of malformation, and these lymphatic vessels produce some chemokines that induce intralymphatic aggregation of macrophages. PMID- 27256926 TI - Obesity, hypertension, social determinants of health and the epidemiologic transition among traditional Amazonian populations. AB - BACKGROUND: The health and nutritional situation of adults from three rural vulnerable Amazonian populations are investigated in relation to the Social Determinants of Health (SDH) and the epidemiologic transition. AIM: To investigate the role of the environment and the SDH on the occurrence of chronic degenerative diseases in these groups. SUBJECTS AND METHODS: Anthropometric, blood pressure and demographic data were collected in adults from the RDS Mamiraua, AM (n = 149), Flona Caxiuana, PA (n = 148) and quilombolas, PA (n = 351), populations living in a variety of socio-ecological environments in the Brazilian Amazon. RESULTS: Adjusting for the effect of age, quilombola men are taller (F = 9.85; p < 0.001) and quilombola women present with higher adiposity (F = 20.43; p < 0.001) and are more overweight/obese. Men from Mamiraua present higher adiposity (F = 9.58; p < 0.001). Mamiraua women are taller (F = 5.55; p < 0.01) and have higher values of waist circumference and subscapular/triceps index. Quilombolas present higher prevalence of hypertension in both sexes and there are significant differences in rates of hypertension among the women (chi(2) = 17.45; p < 0.01). The quilombolas are more dependent on government programmes, people from Mamiraua have more economic resources and the group from Caxiuna have the lowest SES. CONCLUSION: In these populations, the SDH play a key role in the ontogeny of diseases and the 'diseases of modernity' occur simultaneously with the always present infectoparasitic pathologies, substantially increasing social vulnerability. PMID- 27256928 TI - Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis. AB - Atherosclerosis is a progressive disease in which endothelial cell dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation, lead to the loss of vascular homeostasis. Oxidized low-density lipoprotein (oxLDL) may play a pre-eminent function in atherosclerotic lesion formation, even if their role is still debated. Several types of scavenger receptors (SRs) such as SR-AI/II, SRBI, CD36, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), toll-like receptors (TLRs) and others can promote the internalization of oxLDL. They are expressed on the surface of vascular wall cells (endothelial cells, macrophages and smooth muscle cells) and they mediate the cellular effects of oxLDL. The key influence of both oxLDL and SRs on the atherogenic process has been established in atherosclerosis-prone animals, in which antioxidant treatment and/or silencing of SRs has been shown to reduce atherogenesis. Despite some discrepancies, the indication from cohort studies that there is an association between oxLDL and cardiovascular (CV) events seems to point toward a role for oxLDL in atherosclerotic plaque progress and disruption. Finally, randomized clinical trials using antioxidants have demonstrated benefits only in high-risk patients, suggesting that additional proofs are still needed to better define the involvement of each type of modified LDL in the development of atherosclerosis. PMID- 27256927 TI - Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia. AB - OBJECTIVE: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms-like tyrosine kinase 1 (sFlt-1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt-1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt-1, PlGF and the sFlt-1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE. METHODS: Serum sFlt-1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22-MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum. RESULTS: During pregnancy, higher levels of sFlt-1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P < 0.0001). Further, sFlt-1 and the sFlt-1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all P < 0.0001). At 1 year postpartum, levels of sFlt-1 and the sFlt 1/PlGF ratio had decreased in both groups; however, their levels in the PE group were still higher than in the controls (P = 0.001 and < 0.0001, respectively). Levels of sFlt-1 and the sFlt-1/PlGF ratio remained positively correlated with intima thickness and I/M ratio at 1 year postpartum. CONCLUSIONS: Higher sFlt-1 levels and sFlt-1/PlGF ratio in women with PE were positively associated with signs of arterial aging during pregnancy. At 1 year postpartum, sFlt-1 levels and the sFlt-1/PlGF ratio were still higher in the PE group and were associated with the degree of arterial aging. (c) 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. PMID- 27256929 TI - Karyotypic Evolution in Malagasy Flying Foxes (Pteropodidae, Chiroptera) and Their Hipposiderid Relatives as Determined by Comparative Chromosome Painting. AB - Pteropodidae and Hipposideridae are 2 of the 9 chiropteran families that occur on Madagascar. Despite major advancements in the systematic study of the island's bat fauna, few karyotypic data exist for endemic species. We utilized G- and C banding in combination with chromosome painting with Myotismyotis probes to establish a genome-wide homology among Malagasy species belonging to the families Pteropodidae (Pteropus rufus 2n = 38; Rousettus madagascariensis, 2n = 36), Hipposideridae (Hipposideros commersoni s.s., 2n = 52), and a single South African representative of the Rhinolophidae (Rhinolophus clivosus, 2n = 58). Painting probes of M. myotis detected 26, 28, 28, and 29 regions of homology in R. madagascariensis, P. rufus, H. commersoni s.s, and R. clivosus, respectively. Translocations, pericentric inversions, and heterochromatin additions were responsible for karyotypic differences amongst the Malagasy pteropodids. Comparative chromosome painting revealed a novel pericentric inversion on P. rufus chromosome 4. Chromosomal characters suggest a close evolutionary relationship between Rousettus and Pteropus. H. commersoni s.s. shared several chromosomal characters with extralimital congeners but did not exhibit 2 chromosomal synapomorphies proposed for Hipposideridae. This study provides further insight into the ancestral karyotypes of pteropodid and hipposiderid bats and corroborates certain molecular phylogenetic hypotheses. PMID- 27256930 TI - Prospective comparison of search strategies for systematic reviews: an objective approach yielded higher sensitivity than a conceptual one. AB - BACKGROUND: In the development of search strategies for systematic reviews, "conceptual approaches" are generally recommended to identify appropriate search terms for those parts of the strategies for which no validated search filters exist. However, "objective approaches" based on search terms identified by text analysis are increasingly being applied. OBJECTIVES: To prospectively compare an objective with a conceptual approach for the development of search strategies. METHODS: Two different MEDLINE search strategies were developed in parallel for five systematic reviews covering a range of topics and study designs. The Institute for Quality and Efficiency in Health Care (IQWiG) applied an objective approach, and external experts applied a conceptual approach for the same research questions. For each systematic review, the citations retrieved were combined and the overall pool of citations screened to determine sensitivity and precision. RESULTS: The objective approach yielded a weighted mean sensitivity and precision of 97% and 5%. The corresponding values for the conceptual approach were 75% and 4%. CONCLUSION: Our findings indicate that the objective approach applied by IQWiG for search strategy development yields higher sensitivity than and similar precision to a conceptual approach. The main advantage of the objective approach is that it produces consistent results across searches. PMID- 27256931 TI - Orbitide Composition of the Flax Core Collection (FCC). AB - The flax (Linum usitatissimum L.) core collection (FCC) was regenerated in Saskatoon, Saskatchewan and Morden, Manitoba in 2009. Seed orbitide content and composition from successfully propagated plants of 391 accessions were analyzed using high-throughput analyses employing high-performance liquid chromatography (HPLC) with reverse-phase monolithic HPLC columns and diode array detection (HPLC DAD). Seed from plants regenerated in Morden had comparatively higher orbitide content than those grown in Saskatoon. Concentrations of orbitides encoded by contig AFSQ01016651.1 (1, 3, and 8) were higher than those encoded by AFSQ01025165.1 (6, 13, and 17) for most accessions in both locations. The cultivar 'Primus' from Poland and an unnamed accession (CN 101580 of unknown origin) exhibited the highest ratio of sum of [1,3,8] to a sum of [6,13,17]. Conversely, the lowest orbitide concentrations and ratio of [1,3,8] to [6,13,17] were observed in cultivars 'Hollandia' and 'Z 11637', both from The Netherlands. Orbitide expression did not correlate with flax morphological and other chemical traits. PMID- 27256932 TI - Remembering: A Transformational Leader in Psychiatric Mental Health Nursing and a Mentor, Grayce M. Sills (1926-2016). PMID- 27256933 TI - Factors of Depressive Symptoms Among Elementary, Middle, and High School Students. AB - Little attention has been paid to the individual, family, friends, and school profiles of depressed children during the transition from childhood to adolescence. This study aimed to describe the evolution of factors associated with depressive symptoms among elementary, middle, and high school students. This was a secondary analytic study using three datasets of a cohort of Korean children or adolescents. Children or adolescents with depressed symptoms reported lower self-esteem, peer attachment, academic performance, and adaptability in school. Other risk factors for depressive symptoms that included gender, obesity, family conflict, and with whom they discussed personal issues showed different patterns from the elementary school years to high school years. A sex difference (female>male) of depressive symptoms was evident only among high school students. Influences including individuals, family, friends, and school factors for adolescents varied depending upon school years. Understanding the correlates/risk factors could guide the screening and management of depressive symptoms. PMID- 27256934 TI - Mental Health Service Users' Experiences of Training Focused on Empowerment: Training Environment and the Benefits of Training. AB - This qualitative study investigated the mental health service users' (MHSUs') experiences of empowerment training and it was based on individual interviews with 24 MHSUs. Findings showed that MHSUs described the training environment through three dimensions: social interaction, learners' internal resources and the pedagogical execution of training. The training reinforced their positive internal resources, stimulated their inner mind activity and gave meaning to their lives. The knowledge of the training environment helps to build environment, which will support MHSUs' training. Empowerment training could be used to strengthen MHSUs' positive internal resources giving them also a possibility to train their cognitive activities. PMID- 27256935 TI - The Prevalence of Antenatal Depression and its Related Factors in Chinese Pregnant Women who Present with Obstetrical Complications. AB - OBJECTIVES: The psychological status of Chinese pregnant women who present with obstetrical complications is concerning to Chinese health professionals. This study aimed to investigate the prevalence of antenatal depression and analyzed related risk factors in a population of high-risk Chinese women. DESIGN: A large sample size, cross-sectional study. METHODS: A total of 842 pregnant women with complications completed the Chinese version of the Postpartum Depression Screen Scale (PDSS) in this cross-sectional study. t-Test, ANOVA and Binary logistic regression tests were used in data analysis of antenatal depression and risk factors. RESULTS: The prevalence of major or minor depression in high-risk Chinese pregnant women during antenatal period was 8.3% and 28.9%, respectively. Independent-sample t-test and two-way analysis of variance (ANOVA) indicated significant differences in age, education, occupation and the number of complications (P<0.05). Binary logistic regression analysis indicated a significant negative association between depression and education (P<0.01) with lower educational level (OR: 0.590; 95% CI: 0.424-0.820) associated with a higher risk for depression. A significant positive association was observed between depression and age (P<0.05) with higher age (OR: 1.338; 95% CI: 1.008-1.774) correlated with a higher risk for depression. CONCLUSIONS: Women who experienced obstetric complications presented with higher PDSS depression scores. Screening for antenatal depression in high-risk pregnant women to promote early detection of depression and reduce health risks for universal health promotion is recommended. PMID- 27256936 TI - The Effect of a Drug Adherence Enhancement Program on the Drug Adherence Behaviors of Patients With Major Depressive Disorder in Thailand: A Randomized Clinical Trial. AB - This study aimed to compare drug adherence behaviors during the sixth week between patients with first diagnosed major depressive disorder who received the Drug Adherence Enhancement Program and those who received only the usual care. A randomized clinical trial, post-test only design was conducted in the outpatient unit of a medical school hospital in Bangkok, Thailand. The experimental and control groups consisted of 30 and 26 participants respectively. Participants in the experimental group exhibited significantly higher drug adherence behaviors than the control group. This is important for nurses in promoting adherence to antidepressant drugs for patients with first diagnosed major depressive disorder. PMID- 27256937 TI - Emotions, Ideas and Experiences of Caregivers of Patients With Schizophrenia About "Family to Family Support Program". AB - "Family to Family Support Program" is a significant intervention program to assist families by informing them about treatment procedures and coping strategies, increasing their functionality, helping them to overcome the challenges of the disease. This study was particularly designed to investigate the emotions, thoughts, and experiences of caregivers of schizophrenia patients who participated in "Family to Family Support Program." The study was conducted with one of the qualitative research methods, phenomenological method. The study sample included caregivers who care for schizophrenia patients and participated in the "Family to Family Support Program". Twenty caregivers were included in the sample. The study was carried out in Izmir Schizophrenia Support Association. The study data were collected with four open ended questions. The average age of the participants was 56,77 +/- 72,89, 10 male caregivers and 10 female caregivers, 9 caregivers were fathers, 6 caregivers were mothers, and 5 of them were siblings. The thematic analysis indicated that the emotions, thoughts and experiences of caregivers can be categorized in four groups: "I learned to deal with my problems", "I am conscious in my interaction with the patient and I know and I am not alone", "I feel much better", and "Schizophrenia is not the end of the road, knowledge sorts things out." Caregivers who participated in "Family to Family Support Program" expressed their satisfaction that they were benefited from the program, their coping skills were improved, they experienced less challenges when providing care, they understood the disease better, and it felt comfortable. PMID- 27256938 TI - Attempted Suicide Triggers in Thai Adolescent Perspectives. AB - The study goal was to describe attempted suicide triggers in Thai adolescents. A descriptive exploratory qualitative study approach was used utilizing in-depth interviews with twelve adolescents who had attempted suicide and six of their parents. Content analysis was conducted. Attempted suicide triggers were (1) severe verbal criticisms and expulsion to die by a significant family member, (2) disappointed and unwanted by boyfriend in first serious relationship, (3) unwanted pregnancy, and (4) mental illness leading to intense emotions and irresistible impulses. These attempted suicide triggers should be of concern and brought into suicide prevention management programs such as emotional management, effective communication for adolescents and family. PMID- 27256939 TI - Ward Climate Within a High Secure Forensic Psychiatric Hospital: Perceptions of Patients and Nursing Staff and the Role of Patient Characteristics. AB - Within this study the relationship between patient characteristics (age, length of stay, risk, psychopathy) and individual perceived ward climate (n=83), and differences between staff's and patient perceptions of climate (n=185) was investigated within a high secure forensic hospital. Results show that therapeutic hold was rated higher among staff compared to patients, while patients held a more favorable view on patient cohesion and experienced safety. Furthermore, patient characteristics (age, risk and psychopathy) were found to be related with individual ratings of ward climate. The findings underline the importance of assessing ward climate among both patients and staff in clinical practice. PMID- 27256940 TI - Depression and Social Support Trajectories During 1 Year Postpartum Among Marriage-Based Immigrant Mothers in Taiwan. AB - OBJECTIVES: This panel study examined the trajectories of depression and social support during the first year postpartum among marriage-based immigrant mothers in Taiwan, and the effect of social support on depression. METHODS: This panel study recruited South-Asia immigrant mothers (mean age: 27years) to complete structured questionnaire at 1month, 6month, and 1year postpartum. A total of 203 immigrant mothers completed structured questionnaires at 1 and 6months, and 163 completed the questionnaires at 1year postpartum. Postpartum depression was measured using the Edinburgh Postpartum Depression Scale. Social support was composed of 3 subscales, emotional, instrumental, and informational support. Hierarchical linear modeling was used to examine the relationships between trajectories and factors associated with depression. RESULTS: Depression and instrumental support followed downward curvilinear trajectories, while emotional and informational support followed upward curvilinear trajectories. Depression was highest at 1month, decreased sharply until 6months, and then leveled off between 6 and 12months. Emotional and instrumental support negatively covaried with postpartum depression over time. When the three-dimensional supports were considered together, only emotional support retained its significance. CONCLUSIONS: Our results demonstrated that depression was highest at 1month, then decreased, and then leveled off during 1year postpartum, though further study may be needed to confirm the trajectory. The 3 types of social support differed in postpartum trajectory, suggesting the needs to consider them separately in future studies. To decrease postpartum depression among immigrant mothers, strategies should be developed to increase emotional and instrumental support during postpartum period. PMID- 27256941 TI - Effectiveness of Structured Education in Reduction of Postpartum Depression Scores: A Quasi-Experimental Study. AB - The aim of this study was to evaluate effectiveness of structured education in reduction of postpartum depression scores among women. This was a quasi experimental study with a pre-post tests and a control group. Non-random sampling was used and the study included a total of 103 Turkish women, 52 of whom were in the intervention group and 51 were in the control group. The women in the intervention group were offered structured education for postpartum depression and given structured education material. Effectiveness of the education given was evaluated by comparing scores for Edinburg Postpartum Depression Scale obtained before and after delivery between the intervention and the control groups. Before education, median score (8.0+/-4.8) for Edinburg Postpartum Depression Scale of the intervention group were significantly higher the than the control group (6.0+/-6.0, p=0.010), but the groups were statistically similar in terms of having depression (intervention: 17.3%, control: 11.8%, p=0.425). After education, the median score for Edinburg Postpartum Depression Scale and the ratio of the women having depression in the intervention group were significantly lower than in the control group (respectively intervention: 4.0+/-3.0, control: 10.0+/-4.0, p=0.000; intervention: 7.7%, control: 25.5%, p=0.015). Besides, the median score (8.0+/-4.8) of the intervention group before education were significantly higher than the score (4.0+/-3.0) obtained after education (p=0.000), while the median score (6.0+/-6.0) of the control group before education were lower than the score (10.0+/-4.0) obtained after education (p=0.000). This study revealed that structured education offered to women by nurses was effective in reducing the postpartum depression scores and the numbers of women having depression. PMID- 27256942 TI - Auditory Hallucinatory Beliefs in Patients With Schizophrenia: Association of Auditory Hallucinations With Social Interactions, Characteristics and Emotional Behaviors Over 3 Months. AB - The aims of this study were to explore social interactions, characteristics, and emotional behaviors to detect changes in auditory hallucinatory beliefs in patients with schizophrenia over a 3-month period. Participants (n=189) were evaluated using the Auditory Hallucinations Assessment Scale (AHAS) and the Assessment of Communication and Interaction Skills (ACIS). The characteristics and emotional behaviors measured by the AHAS showed improvements, while auditory hallucinatory beliefs became less influential. Social interaction scores increased regardless of changes in auditory hallucinatory beliefs. Psychiatric professionals need to train those who hear voices to react to them with indifference. PMID- 27256943 TI - Concept Analysis of Illness Engulfment in Schizophrenia. AB - Schizophrenia has a significant risk of damaging an individual's self-concept. Through the process of illness engulfment an individual's self-concept becomes reorganized entirely around the experience of having schizophrenia. The purpose of this manuscript is to clarify the structure and function of the concept of illness engulfment in schizophrenia using Walker and Avant's (2011) method of concept analysis. Data came from a review of scholarly literature, as well as contemporary and historical art, literature, music, and other media forms. The analysis discussed two defining attributes of experience of illness and impact on self-concept with a total of seven indicators. The article listed antecedents, consequences, and discussed the Modified Engulfment Scale as empirical referents. Fictional cases were developed to illustrate the concept. Finally, the concept of illness engulfment was discussed within the framework of the Roy Adaptation Model. PMID- 27256944 TI - Research on the Effect of the Foot Bath and Foot Massage on Residual Schizophrenia Patients. AB - Researchers performed foot baths and massages for residual schizophrenia patients to gauge the effects on psychiatric symptoms. Subjects were six residual schizophrenia patients hospitalized in a psychiatric hospital. Three times a week for 4weeks, they received an 8-minute effleurage massage to their legs after a 10 minute foot bath. The effect of physiological relaxation was identified by a significant decline in heart rate in all cases. The results of the Positive and Negative Symptom Scale are as follows: a mean score of 29.0 was measured before treatment, which lowered to 21.5 after treatment, indicating that foot care improved their negative symptoms (p<0.05).The results of the Quality of Life Scale before the foot care intervention, were 10.5 and increased to 34.0 after the intervention, indicating improvement in their quality of life (p<0.05). The results of the two measurements indicate that foot baths and massages were effective in improving psychiatric symptoms. PMID- 27256946 TI - Examining Patterns and Functions of Reminiscence in a Sample of Black Adults: Implications for Psychiatric Nurses. AB - The patterns and functions of reminiscence have been shown to be associated with mental health and well-being. The purpose of this study was to examine age and gender differences in the patterns and functions of reminiscence among a sample of Black adults. Multivariate analysis of variance findings revealed age and gender differences on specific reminiscence functions. Age groups >70 scored highest on the Teach/ Inform function. Men reminisce more for Bitterness Revival while women reminisce more frequently to Teach/Inform and for Intimacy Maintenance. Results indicate there are age and gender differences in the reasons why and how often the participants in this study reminisce for a specific purpose. These findings are informative for psychiatric nurses in order to facilitate therapeutic reminiscence to improve the mental health and well-being of this underserved population. PMID- 27256945 TI - The Violence Prevention Community Meeting: A Multi-Site Study. AB - OBJECTIVE: The Violence Prevention Community Meeting (VPCM) is a specialized form of community meeting in which avoiding violence and promoting non-violent problem solving and interpersonal civility are focal points. A nationwide study to assess the VPCM as an effective intervention to reduce workplace violence was undertaken. PARTICIPANTS: Seven acute locked psychiatric units of the Veterans Health Administration (VHA) throughout the United States participated in the study. METHODS: All patients and all staff on the seven in-patient locked psychiatry units participated in the intervention (VPCM) or as a control (treatment as usual). The study was 21weeks at each site. The three time periods were pre-treatment weeks 1-3, treatment weeks 4-18, and post-treatment weeks 19 21. The VPCM was conducted during the treatment weeks. RESULTS: Overall rates of aggression declined by 0.6% (95% CI: -5.6%, 6.5%; nonsignificant) per week in the intervention hospitals and by 5.1% (95% CI: 0.4%, 9.6%; significant) per week for the control hospitals. CONCLUSIONS: Aggression decreased for both the intervention and control hospitals which could be due to enrollment in a research study and thus being more aware of their ability to address workplace violence at their site. PMID- 27256947 TI - The Experience of Women Veterans Coming Back from War. AB - Issues surrounding mental health are common for women veterans who have served in Iraq and Afghanistan wars. The goal of this phenomenological study was to document themes in the stories gathered from eight women veterans who had come back from war. Themes in the stories were: arriving with mixed sentiments; evolving to a changed view of self; permeating aggravation; confounding broken relationships, frequent deployments, and change in military status; remembering war experiences; and seeking opportunity for what is possible. Mental health issues can be observed in the themes. Including story as part of the mental health visit with veterans may be beneficial to veterans as they deal with the transition of coming back. PMID- 27256948 TI - Descriptions and Correlates of Medication Adherence, Attitudes, and Self-Efficacy in Outpatients With Schizophrenia Spectrum Disorders (SSDs). AB - The problem of medication adherence in schizophrenia spectrum disorders (SSDs) has challenged researchers and clinicians for decades. Few investigations have examined non-psychiatric adherence in this group. We conducted a descriptive correlational investigation of adherence and related factors in 185 stable outpatients with SSDs. Fifty-seven percent of participants had antipsychotic medication levels within therapeutic range and 42% had levels below therapeutic range. Pill count percentage adherence to antipsychotic medications ranged from 0 100% with a mean of 70% and SD 34.9. Mean non-psychiatric medication adherence ranged from 0 to 100 with a mean of 61% and SD 31.8. The following characteristics were not significantly associated with adherence: age, diagnosis, gender, race, living arrangement, educational level, typical versus atypical antipsychotic medication. Level of symptoms was correlated negatively and significantly with self-reported medication adherence and medication adherence self-efficacy. Our next project will examine the effectiveness of a telephone delivered intervention designed to support adherence in this group. PMID- 27256949 TI - A Comparative Study of Self-Efficacy for Social Participation of People with Mental Illness in Japan and China. AB - Self-efficacy for social participation (SESP) of people with mental illness was examined in urban areas of Japan and China. The subjects were 266 people (140 Japanese, 126 Chinese) with mental illness who were living in their local community. Our SESP scale (SESP27) and the Rosenberg Self-Esteem Scale, Norbeck Social Support Questionnaire (NSSQ), Sense of Coherence measure (SOC13), General Health Questionnaire (GHQ12), and a self-administered questionnaire related to living conditions were used for data collection. Data were analyzed descriptively, correlations between scales were examined, and multiple regression analysis was performed by country. The results showed that annual income was related to SESP in Japan and China. Therefore, improvement of welfare and employment support for economic independence is likely to improve SESP of people with mental illness in both countries. In addition, SESP in people with mental illness is affected by self-esteem in Japan, and coping skills such as improvement of life functions in China. Thus, SESP is affected differently by the social, cultural and institutional characteristics of each country. PMID- 27256950 TI - Sexual Assault Victims Participating in Research: Causing Harm When Trying to Help? AB - For fear of causing unnecessary distress, ethical concerns have been raised in regard to asking vulnerable persons e.g. sexually traumatized victims to participate in scientific research studies. The current study investigates how victims of sexual assault perceived participating in scientific research in regard to victims' psychological and/or physiological distress and potential beneficial outcomes from participation (N=51). Results from interviews with victims indicated that the majority of victims of sexual assault who had taken part in the study considered their participation in research a positive experience causing little short- or long-term psychological or physiological distress. In addition, over half of the respondents reported some benefits from participation. PMID- 27256951 TI - An Integrative Review of Postpartum Depression in Rural U.S. Communities. AB - AIM: This study's aim is to synthesize and summarize the literature on postpartum depression (PPD) in U.S. rural populations. BACKGROUND: Internationally, PPD has a high prevalence in rural communities. Although women in rural U.S. communities have higher rates of depression outside of the postpartum time period, little study has been conducted on PPD in U.S. rural populations. It is unknown whether rural women in the United States have high rates of PPD as is common in rural populations internationally. DESIGN: We used integrative literature review using Whittemore and Knafl's (2005) methodology. DATA SOURCES AND METHODS: We searched the databases MEDLINE, CINAHL, PsycINFO, and Academic Search Premier with the words "postpartum depression" or "postnatal depression" and the word "rural." RESULTS: We found 11 articles with empirical data that met the criteria and thus were included in the review. Seven articles were quantitative, two were qualitative, one was mixed methods, and one was a nonexperimental design. Five foci emerged in the literature including (a) screening and prevalence, (b) demographic factors, (c) program creation and implementation, (d) mental health care seeking, and (e) social support. The results suggest that prevalence of PPD may be higher in rural U.S. areas, that implementing PPD prevention and screening programs for rural women is feasible, and that women in rural areas rely on informal networks and may face a stigma for seeking mental health care. CONCLUSIONS: Further research is needed on PPD in rural U.S. POPULATIONS: Specifically, this research should focus on the mix of variables found throughout this review such as race and income level. Nurses should lead for changes in clinical practice and policy that increase screening and interventions for PPD in rural communities. PMID- 27256952 TI - Integrating the 2013 Psychiatric Mental Health NP Competencies Into Educational Programs: Where Are We Now? AB - Since the introduction of the revised National Organization of Nurse Practitioner Faculties (NONPF) Nurse Practitioner Core Competencies and Population Focused Psychiatric Mental Health Nurse Practitioner (PMHNP) Competencies, a national forum took place to hear from many PMHNP program directors in the field comparing how they have integrated the lifespan competencies and the master's (MS)/or doctor of nurse practice (DNP) essentials into their curriculum. In this paper, we will report first on the major areas of change in the structure and content of the PMHNP-lifespan curriculum as well as the comments made by many faculty from across the country as to challenges and innovative strategies used to meet these challenges. We will review some of the major issues in content, pedagogy, and evaluation methods as well as examples of how these curricular elements have been infused into select programs across the country. We conclude highlighting several key areas, suggested foci for change, and how the specialty might focus attention and accelerate the significant growth we are seeing in PMHNP programs. PMID- 27256953 TI - Eradicating Barriers to Mental Health Care Through Integrated Service Models: Contemporary Perspectives for Psychiatric-Mental Health Nurses. AB - There has been renewed, global interest in developing new and transformative models of facilitating access to high-quality, cost-effective, and individually centered health care for severe mentally-ill (SMI) persons of diverse racial/ethnic, cultural and socioeconomic backgrounds. However, in our present day health-service delivery systems, scholars have identified layers of barriers to widespread dispersal of well-needed mental health care both nationally and internationally. It is crucial that contemporary models directed at eradicating barriers to mental health services are interdisciplinary in context, design, scope, sequence, and best-practice standards. Contextually, nurses are well positioned to influence the incorporation and integration of new concepts into operationally interdisciplinary, evidence-based care models with measurable outcomes. The aim of this concept paper is to use the available evidence to contextually explicate how the blended roles of psychiatric mental health (PMH) nursing can be influential in eradicating barriers to care and services for SMI persons through the integrated principles of collaboration, integration and service expansion across health, socioeconomic, and community systems. A large body of literature proposes that any best-practice standards aimed at eliminating barriers to the health care needs of SMI persons require systematic, well coordinated interdisciplinary partnerships through evidence-based, high-quality, person-centered, and outcome-driven processes. Transforming the conceptual models of collaboration, integration and service expansion could be revolutionary in how care and services are coordinated and dispersed to populations across disadvantaged communities. Building on their longstanding commitment to individual and community care approaches, and their pivotal roles in research, education, leadership, practice, and legislative processes; PMH nurses are well positioned to be both influential and instrumental in the development of innovative, revolutionary, and transformative paradigmatic models aimed at eradicating treatment barriers, promoting well-being, and reducing preventable mortalities and morbidities among SMI persons. PMID- 27256954 TI - Trauma-Informed Care for Youth in Foster Care. AB - For decades, evidence has shown an undeniable connection between childhood trauma and chronic adverse reactions across the lifespan (Bilchik & Nash, 2008; Perry, 2001; Perry, 2006). Childhood traumatic experiences are associated with serious and persistent, long-term physical, psychological, and substance abuse issues. In addition to adverse effects on physical health, research indicates that early childhood trauma has particularly adverse effects on adolescent self-esteem, coping skills, school performance, self-regulation, critical thinking, self motivation, and the ability to build healthy relationships (O'Connell, Boat, & Warner, 2009). A traumatic event is a dangerous or distressing experience, outside the range of usual human experience that overwhelms the capacity to cope and frequently results in intense emotional and physical reactions, feelings of helplessness and terror, and threatens serious injury or death (The National Child Traumatic Stress Network [NCTSNET], 2014). Approximately five million children each year in the United States experience some type of traumatic experience (Perry, 2006). Nationwide community studies estimate between 25% and 61% of children and adolescents have a history of at least one exposure to a potentially traumatic event and 38.5% of American adults claim to have experienced at least one traumatic event before the age of 13 (Briggs et al., 2012; Gerson & Rappaport, 2013). According to results of a 2002-2003 survey of 900 New York City adolescents, 24% reported a history of witnessing someone being shot, 12% reported exposure to someone being killed, and 51% reported witnessing someone being beaten or mugged (O'Connell et al., 2009). Each year, 2-3 million children are victims of maltreatment, a type of trauma, including physical and/or sexual abuse (U.S. Department of Health and Human Services, 2014; Perry, 2006). Compared to the general population, youth in foster care are significantly more likely to have experienced violence, specifically abuse and/or neglect (Burns et al., 2004). It is estimated that approximately 90-percent of children in foster care have experienced a traumatic event, with nearly half reporting exposure to four or more types of traumatic events (Stein et al., 2001). Given the widespread prevalence of traumatic exposures, it is important for the mental health professionals working with foster care youth, to be aware of the prevalence and various types of trauma that are most common. Focus in treatment is typically on behavioral and emotional reactions rather than addressing the context of these symptoms, including trauma exposure histories and trauma-specific reactions. Clinicians must maintain awareness of the frequency and impact of childhood traumatic experiences on subsequent behaviors and overall functioning. Clinicians should appreciate the link between how traumatized children understand the world and interact with others differently from other children and how to provide appropriate treatment for children with a history of traumatic exposures. Practitioners must remain alert to symptoms that may suggest a history of trauma and must have an understanding of the difficulties adolescents may face regulating their emotions and behavior, as a symptom of a past traumatic experience. The failure to address trauma through screening, assessment, and treatment has major implications for long-term public health costs and services. PMID- 27256955 TI - Designer Drugs and the Impact on the Adolescent User. AB - There are serious concerns regarding adolescent use of designer drugs. Designer drug usage is often undetected and can result in life-threatening physical and psychiatric reactions. This article explores the history of designer drugs, identifies some of the more recent designer drugs available, distinguishes the symptoms of designer drugs usage, and identifies reasons the designer drugs are popular with our young population. Lastly, this paper addresses what nurses can do to facilitate early and proper treatment to reduce serious physiological damage and death that can result from not detecting the use of designer drugs. PMID- 27256956 TI - Comparison of PCR-based methods for the simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in clinical samples. AB - BACKGROUND: Several in-house PCR-based assays have been described for the detection of bacterial meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from clinical samples. PCR-based methods targeting different bacterial genes are frequently used by different laboratories worldwide, but no standard method has ever been established. The aim of our study was to compare different in-house and a commercial PCR-based tests for the detection of bacterial pathogens causing meningitis and invasive disease in humans. METHODS: A total of 110 isolates and 134 clinical samples (99 cerebrospinal fluid and 35 blood samples) collected from suspected cases of invasive disease were analyzed. Specific sets of primers frequently used for PCR diagnosis of the three pathogens were used and compared with the results achieved using the multiplex approach described here. Several different gene targets were used for each microorganism, namely ctrA, crgA and nspA for N. meningitidis, ply for S. pneumoniae, P6 and bexA for H. influenzae. RESULTS: All used methods were fast, specific and sensitive, while some of the targets used for the in-house PCR assay detected lower concentrations of genomic DNA than the commercial method. An additional PCR reaction is described for the differentiation of capsulated and non-capsulated H. influenzae strains, the while commercial method only detects capsulated strains. CONCLUSIONS: The in-house PCR methods here compared showed to be rapid, sensitive, highly specific, and cheaper than commercial methods. The in house PCR methods could be easily adopted by public laboratories of developing countries for diagnostic purposes. The best results were achieved using primers targeting the genes nspA, ply, and P6 which were able to detect the lowest DNA concentrations for each specific target. PMID- 27256957 TI - A validated stability-indicating ultra performance liquid chromatography method for the determination of potential process-related impurities in eplerenone. AB - A simple, sensitive, and accurate stability-indicating analytical method has been developed and validated using ultra high performance liquid chromatography. The developed method is used to evaluate the related substances of eplerenone (EP). The degradation behavior of EP under stress conditions was determined, and the major degradants were identified by ultra high performance liquid chromatography with tandem mass spectrometry. The chromatographic conditions were optimized using an impurity-spiked solution, and the samples, generated from forced degradation studies. The resolution of EP, its potential impurities, and its degradation products was performed on a Waters UPLC BEH C18 column (50 * 2.1 mm, 1.7 MUm) by linear gradient elution using a mobile phase consisting of 10 mmol/L ammonium acetate adjusted to pH 4.5, methanol and acetonitrile. A photo-diode array detector set at 245 nm was used for detection. The flow rate was set at 0.3 mL/min. The procedure had good specificity, linearity (0.02-3.14 MUg/mL), recovery (96.1-103.9%), limit of detection (0.01-0.02 MUg/mL), limit of quantitation (0.03-0.05 MUg/mL), and robustness. The correction factors of the process-related substances were calculated. PMID- 27256958 TI - Analgesic use and pain in residents with and without dementia in aged care facilities: A cross-sectional study. AB - AIM: To investigate analgesic use and pain in people with and without dementia in Australian residential aged are facilities. METHODS: A cross-sectional study of 383 residents of six residential aged are facilities was conducted. Nurses assessed self-reported and clinician-observed pain. Analgesic use data were extracted from medication charts. Logistic regression was used to investigate factors associated with analgesic use. RESULTS: Analgesics were administered to 291 (76.0%) residents in the previous 24 hours. The prevalence of analgesic use was similar among residents with and without dementia (79.3% vs 73.4%, P = 0.20). Residents with dementia had a higher prevalence of self-reported pain than those without dementia but similar prevalence of clinician-observed pain. In residents with dementia, high care residence and dementia severity were associated with analgesic use. CONCLUSION: The prevalence of analgesic use was similar among residents with and without dementia. Both self-reported and clinician-observed measures are needed in regular pain assessments. PMID- 27256959 TI - Sustainable intensification: a multifaceted, systemic approach to international development. AB - Sustainable intensification (SI) is a term increasingly used to describe a type of approach applied to international agricultural projects. Despite its widespread use, there is still little understanding or knowledge of the various facets of this composite paradigm. A review of the literature has led to the formalization of three principles that convey the current characterization of SI, comprising a whole system, participatory, agroecological approach. Specific examples of potential bottlenecks to the SI approach are cited, in addition to various technologies and techniques that can be applied to overcome these obstacles. Models of similar, succcessful approaches to agricultural development are examined, along with higher level processes. Additionally, this review explores the desired end points of SI and argues for the inclusion of gender and nutrition throughout the process. To properly apply the SI approach, its various aspects need to be understood and adapted to different cultural and geographic situations. New modeling systems and examples of the effective execution of SI strategies can assist with the successful application of the SI paradigm within complex developing communities. (c) 2016 Society of Chemical Industry. PMID- 27256960 TI - Considerations about document of Spanish consensus for the management of patients with advanced radioactive iodine refractory differentiated thyroid cancer (CDT RAI). PMID- 27256962 TI - CSF Gusher in Cochlear Implant Surgery-does it affect surgical outcomes? AB - OBJECTIVES: The purpose of this prospective study was to measure surgical outcomes in cases of cerebrospinal fluid gusher in cochlear implant surgery. MATERIALS AND METHODS: Demographic, radiological, neurophysiological and surgical results were evaluated in nine cases of patients with cerebrospinal fluid gusher during cochlear implant surgery, out of 164 unilateral cochlear implant procedures. Review of literature and our management technique is discussed. RESULTS: Nine cases had cerebrospinal fluid leak during surgery. Out of three cases of incomplete partition type II, two had cerebrospinal fluid gusher while one had milder ooze. Two cases with large vestibular aqueduct syndrome had intraoperative cerebrospinal fluid gusher. Four cases of gusher had no predictable risk factors on clinical history, examination or preoperative radiology. All cases were managed with meticulous packing of round window site without any other additional measures such as lumbar drain or use of tissue glue. These cases showed no symptoms or signs of cerebrospinal fluid leak in the follow up period. CONCLUSION: We recommend careful meticulous packing of the round window around the electrode using periosteum until cerebrospinal fluid leak is controlled in all cases of cerebrospinal fluid gushers. We also recommend a very conservative approach to managing these patients in the immediate postoperative period. PMID- 27256961 TI - Regulation of A disintegrin and metalloproteinase (ADAM) family sheddases ADAM10 and ADAM17: The emerging role of tetraspanins and rhomboids. AB - A disintegrin and metalloprotease (ADAM) 10 and ADAM17 are ubiquitous transmembrane "molecular scissors" which proteolytically cleave, or shed, the extracellular regions of other transmembrane proteins. ADAM10 is essential for development because it cleaves Notch proteins to induce Notch signaling and regulate cell fate decisions. ADAM17 is regarded as a first line of defense against injury and infection, by releasing tumor necrosis factor alpha (TNFalpha) to promote inflammation and epidermal growth factor (EGF) receptor ligands to maintain epidermal barrier function. However, the regulation of ADAM10 and ADAM17 trafficking and activation are not fully understood. This review will describe how the TspanC8 subgroup of tetraspanins (Tspan5, 10, 14, 15, 17, and 33) and the iRhom subgroup of protease-inactive rhomboids (iRhom1 and 2) have emerged as important regulators of ADAM10 and ADAM17, respectively. In particular, they are required for the enzymatic maturation and trafficking to the cell surface of the ADAMs, and there is evidence that different TspanC8s and iRhoms target the ADAMs to distinct substrates. The TspanC8s and iRhoms have not been studied functionally on platelets. On these cells, ADAM10 is the principal sheddase for the platelet collagen receptor GPVI, and the regulatory TspanC8s are Tspan14, 15, and 33, as determined from proteomic data. Platelet ADAM17 is the sheddase for the von Willebrand factor (vWF) receptor GPIb, and iRhom2 is the only iRhom that is expressed. Induced shedding of either GPVI or GPIb has therapeutic potential, since inhibition of either receptor is regarded as a promising anti-thrombotic therapy. Targeting of Tspan14, 15, or 33 to activate platelet ADAM10, or iRhom2 to activate ADAM17, may enable such an approach to be realized, without the toxic side effects of activating the ADAMs on every cell in the body. PMID- 27256963 TI - Interest of vestibular evaluation in sequentially implanted children: Preliminary results. AB - INTRODUCTION: An early acquired or congenital absence of sensory input of the vestibule will lead to severe delayed posturomotor milestones. Previous studies have proven modifications and even complete ipsilateral loss of vestibular function after unilateral cochlear implantation. The objective of this study was to evaluate whether sequential cochlear implantation has an impact on vestibular function. METHODS: Retrospective study from January 2012 to January 2015 including 26 patients. The first stage consisted of determining the vestibular status of 26 hearing impaired children who were candidates for a second cochlear implant. Three months after contralateral implantation, we reevaluated the vestibular function of the same patients. The vestibular evaluation consisted of multiple tests for canal and otolith function. A complete clinical vestibular evaluation was performed, including the head thrust test. This was followed by an instrumental assessment composed of the classic bicaloric test and vestibular evoked myogenic potentials testing with tone bursts. RESULTS: A high prevalence of vestibular dysfunction (69%) was found in our group of unilaterally implanted children. Three patients had a unique functional vestibule at the not yet implanted ear. Vestibular evoked myogenic potentials responses stayed present in 15 of the 19 patients with a VEMP-response before contralateral implantation. Results of the caloric test changed for 6 patients after contralateral implantation. CONCLUSIONS: After contralateral implantation, 37% of our patients manifested modifications of their vestibular status. Intrasubject comparison of bicaloric and vestibular evoked myogenic potentials testing before and after contralateral cochlear implantation showed that canal function was better preserved than saccular function. Seeing the high prevalence of vestibular dysfunction in our test group of unilateral implanted children, sequential implantation must be preceded by a vestibular assessment to prevent complete bilateral vestibular areflexia and its potential consequences. Presence of hyporeflexia at the yet-to-be implanted ear seems to be a situation particularly at risk. PMID- 27256964 TI - Optimal electrode design: Straight versus perimodiolar. AB - The electrode in a cochlear implant (CI) system is a key factor in hearing performance as it is the interface between the device and the auditory pathway of the recipient. The first CI electrodes were straight and thus adopted a lateral wall position. Subsequent innovations include: perimodiolar electrodes designed to lie adjacent to the modiolar wall and thus to provide more spatially-focused stimulation of the spiral ganglion cells; shorter atraumatic straight electrodes for combined electric and acoustic (hybrid) stimulation. This paper explores the relative merits of straight and perimodiolar electrodes in the search for the optimal electrode design with reference to electrodes from Cochlear((r)). PMID- 27256965 TI - Cochlear implantation in children with congenital unilateral deafness: Mid-term follow-up outcomes. AB - OBJECTIVES: Although cochlear implantation is widely used to treat unilateral deafness in adults, very little literature exists on its use and effects on the paediatric population. This report adds to the literature showing the mid-term follow-up outcomes achieved by these children. MATERIAL AND METHODS: Three children with congenital unilateral deafness were studied after implantation. Speech perception in noise, and sound localization ability were evaluated using age-appropriate materials. RESULTS: The preliminary data of our small group of 3 children with congenital unilateral profound hearing loss revealed that up to 3 years post-implantation, congenitally deaf children who received a cochlear implant after 4 years of age do not demonstrate binaural hearing benefits. CONCLUSION: Early intervention in the prelingual phase may be crucial for the development of binaural hearing. PMID- 27256966 TI - Venovenous Extracorporeal Membrane Oxygenation With Prophylactic Subcutaneous Anticoagulation Only: An Observational Study in More Than 60 Patients. AB - Extracorporeal lung support and therapeutic anticoagulation are dogmatically linked for most clinicians in fear of clotting of the extracorporeal circuit. In the last decade, however, we have learned that bleeding complications in the course of extracorporeal membrane oxygenation (ECMO) therapy are common and not occasionally limiting or fatal. Even though international guidelines lowered the PTT-target values, ECMO therapy without anticoagulation has only been reported sporadically in case reports heretofore. This monocentric, observational study was designed to evaluate a protocol for venovenous ECMO therapy without additional anticoagulation. Patients without former thrombotic events solely received thrombosis prophylaxis with 40 mg subcutaneous enoxaparin per day like every critical care patient. After approval by the local ethics committee (Albert Ludwigs-University Freiburg ethics committee, EK 513/14) all consecutive patients treated with venovenous ECMO therapy since introduction of the protocol have been identified. Digital charts of the patients have been evaluated with special regard to bleeding and thrombotic or embolic events or breakdown of the extracorporeal circuit. Sixty-one patients received venovenous ECMO therapy with prophylactic subcutaneous enoxaparin only. Median duration of ECMO therapy was 7 days (2-32). Overall 560 ECMO days have been observed. No system exchange because of thrombotic occlusion was necessary within the permitted 5 days run time of the centrifugal pump. Overall we identified thrombotic complications in four patients. In three of them centrifugal pump after a runtime of more than 5 days unexpectedly stopped completely because of thrombotic occlusion. In all cases pump exchange was performed promptly and patients did not incur hypoxic deficit. One other patient received substitution of blood products and coagulation factor concentrates because of severe bleeding and sustained myocardial infarction the day after. Only 18% of patients presented with essential clinical bleeding after 7 days of therapy. No fatal bleeding event and no intracranial hemorrhage was observed. Patients required only a third of blood product transfusion compared to published data. Venovenous ECMO therapy with prophylactic anticoagulation only was feasible in this study. It was not associated with an increased rate of system exchanges compared to regimes with therapeutic anticoagulation in registry data. It provides the potential to relevantly decrease the incidence of severe bleeding events and blood transfusion requirements. The apodictic adherence to anticoagulation in therapeutic dosage should be critically scrutinized in every patient. PMID- 27256967 TI - Mulibrey nanism: Two novel mutations in a child identified by Array CGH and DNA sequencing. AB - In childhood, several rare genetic diseases have overlapping symptoms and signs, including those regarding growth alterations, thus the differential diagnosis is sometimes difficult. The proband, aged 3 years, was suspected to have Silver Russel syndrome because of intrauterine growth retardation, postnatal growth retardation, typical facial dysmorphic features, macrocephaly, body asymmetry, and bilateral fifth finger clinodactyly. Other features were left atrial and ventricular enlargement and patent foramen ovale. Total X-ray skeleton showed hypoplasia of the twelfth rib bilaterally and of the coccyx, slender long bones with thick cortex, and narrow medullary channels. The genetic investigation did not confirm Silver-Russel syndrome. At the age of 5 the patient developed an additional sign: hepatomegaly. Array CGH revealed a 147 kb deletion (involving TRIM 37 and SKA2 genes) on one allele of chromosome 17, inherited from his mother. These results suggested Mulibrey nanism. The clinical features were found to fit this hypothesis. Sequencing of the TRIM 37 gene showed a single base change at a splicing locus, inherited from his father that provoked a truncated protein. The combined use of Array CGH and DNA sequencing confirmed diagnosis of Mulibrey nanism. The large deletion involving the SKA2 gene, along with the increased frequency of malignant tumours in mulibrey patients, suggests closed monitoring for cancer of our patient and his mother. Array CGH should be performed as first tier test in all infants with multiple anomalies. The clinician should reconsider the clinical features when the genetics suggests this. (c) 2016 Wiley Periodicals, Inc. PMID- 27256968 TI - Medicaid Disenrollment and Disparities in Access to Care: Evidence from Tennessee. AB - OBJECTIVE: To assess the effects of Tennessee's 2005 Medicaid disenrollment on access to health care among low-income nonelderly adults. DATA SOURCE/STUDY SETTING: We use data from the 2003-2008 Behavioral Risk Factor Surveillance System. STUDY DESIGN: We examined the effects of Medicaid disenrollment on access to care among adults living in Tennessee compared with neighboring states, using difference-in-difference models. PRINCIPAL FINDINGS: Evidence suggests that Medicaid disenrollment resulted in significant decreases in health insurance and increases in cost-related barriers to care for low-income adults living in Tennessee. Statistically significant changes were not observed for having a personal doctor. CONCLUSIONS: Medicaid disenrollment is associated with reduced access to care. This finding is relevant for states considering expansions or contractions of Medicaid under the Affordable Care Act. PMID- 27256969 TI - Repartition of oil miscible and water soluble UV filters in an applied sunscreen film determined by confocal Raman microspectroscopy. AB - Photoprotection provided by topical sunscreens is expressed by the sun protection factor (SPF) which depends primarily on the UV filters contained in the product and the applied sunscreen amount. Recently, the vehicle was shown to significantly impact film thickness distribution of an applied sunscreen and sunscreen efficacy. In the present work, repartition of the UV filters within the sunscreen film upon application is investigated for its role to affect sun protection efficacy. The spatial repartition of an oil-miscible and a water soluble UV filter within the sunscreen film was studied using confocal Raman microspectroscopy. Epidermis of pig ear skin was used as substrate for application of three different sunscreen formulations, an oil-in-water emulsion, a water-in-oil emulsion, and a clear lipo-alcoholic spray (CAS) and SPF in vitro was measured. Considerable differences in the repartition of the UV filters upon application and evaporation of volatile ingredients were found between the tested formulations. A nearly continuous phase of lipid-miscible UV filter was formed only for the WO formulation with dispersed aggregates of water-soluble UV filter. OW emulsion and CAS exhibited interspersed patches of the two UV filters, whereas the segregated UV filter domains of the latter formulation were by comparison of a much larger scale and spanned the entire thickness of the sunscreen film. CAS therefore differed markedly from the other two formulations with respect to filter repartition. This difference should be reflected in SPF when the absorption spectra of the employed UV filters are not the same. Confocal Raman microspectroscopy was shown to be a powerful technique for studying this mechanism of sun protection performance of sunscreens. PMID- 27256970 TI - Histopathological Study of Left and Right Atria in Isolated Rheumatic Mitral Stenosis With and Without Atrial Fibrillation. AB - BACKGROUND: Mitral stenosis (MS) has the highest incidence of atrial fibrillation (AF) in chronic rheumatic valvular disease. There are very few studies in isolated MS comparing histopathological changes in patients with sinus rhythm (SR) and AF. OBJECTIVES: To analyze the histological changes associated with isolated MS and compare between changes in AF and SR. METHODS: This was a prospective study in patients undergoing valve replacement surgery for symptomatic isolated MS who were divided into 2 groups, Group I AF (n = 13) and Group II SR (n = 10). Intra-operative biopsies performed from 5 different sites from both atria were analyzed for 10 histopathologic changes commonly associated with AF. RESULTS: On multivariate analysis, myocytolysis (odds ratio [OR]: 1.48, P = 0.05) was found to be associated with AF, whereas myocyte hypertrophy (OR: 0.21, P = 0.003), and glycogen deposition (OR: 0.43, P = 0.002) was associated with SR. Interstitial fibrosis the commonest change was uniformly distributed across both atria irrespective of the rhythm. CONCLUSION: In rheumatic MS, SR is associated with myocyte hypertrophy whereas AF is associated with myocytolysis. Endocardial inflammation is more common in left atrial appendage irrespective of rhythm. Interstitial fibrosis is seen in >90% of patients distributed in both the atria and is independent of the rhythm. Amyloid and Aschoff bodies are uncommon and the rest of the changes are uniformly distributed across both the atria. PMID- 27256972 TI - New therapeutic approaches for ANCA-associated vasculitides. AB - For many years, despite severe side effects, vasculitides have been managed with high doses of corticosteroids and long-lasting intensive immunosuppression. Recent, innovative approaches have improved our knowledge of the disease pathophysiologies leading to novel treatments that are transforming the standard of care, at least for antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs) and again providing new elements to further understanding of the disease mechanisms. Although this could seem to be a virtuous circle of enhanced comprehension and innovation, many questions regarding patient care remain unsolved and a closer look at the past could temper this exciting race to new drug discovery. In this review, we describe the different evidence-based medicine strategies, the drugs that are being tested in AAV patients and novel strategies that should improve AAV treatment. However, the costs and benefits of the development of new treatment strategies are also considered in light of 20 years of clinical trial experience in the field of AAVs. PMID- 27256973 TI - [Comparison of the concept of "responsibility" in neuroscience and in French criminal law: A cross-literature review for the psychiatric forensic practice]. AB - In forensic psychiatry, experts have to determine the level of responsibility of a subject with regard to their acts. Neuroscience and cognitive sciences have been increasingly studying the brain functions that are supposed to underlie individual responsibility. In neuroscience, impairment of responsibility is underlain by disruptions of different types of cognitive processes. This processes are executive functions, theory of mind, agency, volition and empathy. In the juridical conception, the term of responsibility refers to a broader perspective than in the neuroscientific approach. PMID- 27256971 TI - Multisite electrophysiological recordings by self-assembled loose-patch-like junctions between cultured hippocampal neurons and mushroom-shaped microelectrodes. AB - Substrate integrated planar microelectrode arrays is the "gold standard" method for millisecond-resolution, long-term, large-scale, cell-noninvasive electrophysiological recordings from mammalian neuronal networks. Nevertheless, these devices suffer from drawbacks that are solved by spike-detecting, spike sorting and signal-averaging techniques which rely on estimated parameters that require user supervision to correct errors, merge clusters and remove outliers. Here we show that primary rat hippocampal neurons grown on micrometer sized gold mushroom-shaped microelectrodes (gMMUE) functionalized simply by poly-ethylene imine/laminin undergo self-assembly processes to form loose patch-like hybrid structures. More than 90% of the hybrids formed in this way record monophasic positive action potentials (APs). Of these, 34.5% record APs with amplitudes above 300 MUV and up to 5,085 MUV. This self-assembled neuron-gMMUE configuration improves the recording quality as compared to planar MEA. This study characterizes and analyzes the electrophysiological signaling repertoire generated by the neurons-gMMUE configuration, and discusses prospects to further improve the technology. PMID- 27256974 TI - Innovations in autoimmune diseases. PMID- 27256975 TI - Stem cell transplantation and mesenchymal cells to treat autoimmune diseases. AB - Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjogren's disease, polymyositis/dermatomyositis and type II diabetes mellitus have received MSC therapeutically. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed. PMID- 27256976 TI - Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses. AB - Rapid and sensitive diagnostic approaches are of the utmost importance for the detection of humans and animals infected by specific influenza virus subtype(s). Cascade-like diagnostics starting with the use of pan-influenza assays and subsequent subtyping devices are normally used. Here, we demonstrated a novel low density array combining 32 TaqMan((r)) real-time RT-PCR systems in parallel for the specific detection of the haemagglutinin (HA) and neuraminidase (NA) subtypes of avian and porcine hosts. The sensitivity of the newly developed system was compared with that of the pan-influenza assay, and the specificity of all RT qPCRs was examined using a broad panel of 404 different influenza A virus isolates representing 45 different subtypes. Furthermore, we analysed the performance of the RT-qPCR assays with diagnostic samples obtained from wild birds and swine. Due to the open format of the array, adaptations to detect newly emerging influenza A virus strains can easily be integrated. The RITA array represents a competitive, fast and sensitive subtyping tool that requires neither new machinery nor additional training of staff in a lab where RT-qPCR is already established. PMID- 27256977 TI - Medicinal herbs Fructus corni and Semen cuscutae suppress allograft rejection via distinct immune mechanisms. AB - Achieving long-term allograft survival without continuous global immunosuppression is highly desirable because constant immunosuppression causes severe side effects. Traditional Chinese medicine (TCM) has been utilized to treat numerous diseases for centuries. To seek novel immunosuppressive agents, we investigated several Chinese herbal formulas that have been shown to be effective in treating autoimmune diseases. C57BL/6 mice were transplanted with a skin graft from Balb/C donors and treated orally with the TCM. IL-12-expressing dendritic cells and CD4+FoxP3+ Tregs were quantified by flow cytometer while intragraft IL 12 gene expression was measured by real-time PCR. Here we identified a unique TCM, San Si formula, which contains three herbs: Fructus corni (FC), Fructus ligustri lucidi (FLL) and Semen cuscutae (SC). We found that either SC or FC, but not FLL, significantly prolonged skin allograft survival while SC plus FC or San Si formula further delayed allograft rejection compared to SC or FC alone. SC and FC, which did not contain cyclosporine and rapamycin, reduced graft-infiltrating T cells and suppressed their proliferation. Importantly, it was SC, but not FC, that induced CD4+FoxP3+ Tregs in recipients. Tregs induced by SC were also more potent in suppression. In contrast, FC repressed both intracellular IL-12 expression by intragraft DCs and IFNgamma expression by graft-infiltrating T cells. Moreover, FC inhibited intragraft IL-12 gene expression. Depleting Tregs and providing exogenous IL-12 completely reversed allograft survival induced by SC plus FC. Thus, SC and FC synergistically suppress allograft rejection via distinct mechanisms. PMID- 27256978 TI - Run-on of germline apoptosis promotes gonad senescence in C. elegans. AB - Aging (senescence) includes causal mechanisms (etiologies) of late-life disease, which remain poorly understood. According to the recently proposed hyperfunction theory, based on the older theory of antagonistic pleiotropy, senescent pathologies can arise from futile, post-reproductive run-on of processes that in early life promote fitness. Here we apply this idea to investigate the etiology of senescent pathologies in the reproductive system of Caenorhabditis elegans hermaphrodites, particularly distal gonad degeneration and disintegration. Hermaphrodite germ cells frequently undergo "physiological" (non-damage-induced) apoptosis (PA) to provision growing oocytes. Run-on of such PA is a potential cause of age-related gonad degeneration. We document the continuation of germline apoptosis in later life, and report that genetically blocking or increasing PA retards or accelerates degeneration, respectively. In wild-type males, which lack germ line apoptosis, gonad disintegration does not occur. However, mutational induction of PA in males does not lead to gonad disintegration. These results suggest that as germ-cell proliferation rate declines markedly in aging hermaphrodites (but not males), run-on of PA becomes a pathogenic mechanism that promotes gonad degeneration. This illustrates how hyperfunction, or non-adaptive run-on in later life of a process that promotes fitness in early life, can promote atrophic senescent pathology in C. elegans. PMID- 27256980 TI - Dendritic cell-derived VEGF-A plays a role in inflammatory angiogenesis of human secondary lymphoid organs and is driven by the coordinated activation of multiple transcription factors. AB - Lymph node expansion during inflammation is essential to establish immune responses and relies on the development of blood and lymph vessels. Previous work in mice has shown that this process depends on the presence of VEGF-A produced by B cells, macrophages and stromal cells. In humans, however, the cell types and the mechanisms regulating the intranodal production of VEGF-A remain elusive. Here we show that CD11c+ cells represent the main VEGF-A-producing cell population in human reactive secondary lymphoid organs. In addition we find that three transcription factors, namely CREB, HIF-1alpha and STAT3, regulate the expression of VEGF-A in inflamed DCs. Both HIF-1alpha and STAT3 are activated by inflammatory agonists. Conversely, CREB phosphorylation represents the critical contribution of endogenous or exogenous PGE2. Taken together, these results propose a crucial role for DCs in lymph node inflammatory angiogenesis and identify novel potential cellular and molecular targets to limit inflammation in chronic diseases and tumors. PMID- 27256979 TI - Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment. AB - Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. Despite relatively good prognosis a subset of patients shows recurrence, progression and/or metastatic disease, which requires additional treatment. However, neither prognostic nor predictive factors are well specified. Thus, we performed a literature search for the currently available data on disturbances in molecular pathways, cytogenetic changes and results gained by next generation sequencing (NGS) approaches in ONB in order to gain an overview of genetic alterations which might be useful for treating patients with ONB. We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). Furthermore, we compare high- and low-grade ONB, and describe its frequent mimicker: sinonasal neuroendocrine carcinoma. ONB is often a therapeutic challenge, so our goal should be the implementation of acquired knowledge into clinical practice, especially at pretreated, recurrent and metastatic stages. Moreover, the multicenter molecular studies are needed to increase the amount of available data. PMID- 27256981 TI - A Phosphatidic Acid (PA) conveyor system of continuous intracellular transport from cell membrane to nucleus maintains EGF receptor homeostasis. AB - The intracellular concentration of the mitogen phosphatidic acid (PA) must be maintained at low levels until the need arises for cell proliferation. How temporal and spatial trafficking of PA affects its target proteins in the different cellular compartments is not fully understood. We report that in cancer cells, PA cycles back and forth from the cellular membrane to the nucleus, affecting the function of epidermal growth factor (EGF), in a process that involves PPARalpha/LXRalpha signaling. Upon binding to its ligand, EGF receptor (EGFR)-initiated activation of phospholipase D (PLD) causes a spike in intracellular PA production that forms vesicles transporting EGFR from early endosomes (EEA1 marker) and prolonged internalization in late endosomes and Golgi (RCAS marker). Cells incubated with fluorescent-labeled PA (NBD-PA) show PA in "diffuse" locations throughout the cytoplasm, punctae (small, <0.1 MUm) vesicles) and large (>0.5 MUm) vesicles that co-localize with EGFR. We also report that PPARalpha/LXRalpha form heterodimers that bind to new Responsive Elements (RE) in the EGFR promoter. Nuclear PA enhances EGFR expression, a role compatible with the mitogenic ability of the phospholipid. Newly made EGFR is packaged into PA recycling vesicles (Rab11 marker) and transported back to the cytoplasm and plasma membrane. However, a PLD+PA combination impedes binding of PPARalpha/LXRalpha to the EGFR promoter. Thus, if PA levels inside the nucleus reach a certain threshold (>100 nM) PA outcompetes the nuclear receptors and transcription is inhibited. This new signaling function of PLD-PA targeting EGFR trafficking and biphasically modulating its transcription, could explain cell proliferation initiation and its maintenance in cancer cells. PMID- 27256982 TI - Altered splicing leads to reduced activation of CPEB3 in high-grade gliomas. AB - Cytoplasmic polyadenylation element binding proteins (CPEBs) are auxiliary translational factors that associate with consensus sequences present in 3'UTRs of mRNAs, thereby activating or repressing their translation. Knowing that CPEBs are players in cell cycle regulation and cellular senescence prompted us to investigate their contribution to the molecular pathology of gliomas-most frequent of intracranial tumors found in humans. To this end, we performed methylation analyses in the promoter regions of CPEB1-4 and identified the CPEB1 gene to be hypermethylated in tumor samples. Decreased expression of CPEB1 protein in gliomas correlated with the rising grade of tumor malignancy. Abundant expression of CPEBs2-4 was observed in several glioma specimens. Interestingly, expression of CPEB3 positively correlated with tumor progression and malignancy but negatively correlated with protein phosphorylation in the alternatively spliced region. Our data suggest that loss of CPEB3 activity in high-grade gliomas is caused by expression of alternatively spliced variants lacking the B region that overlaps with the kinase recognition site. We conclude that deregulation of CPEB proteins may be a frequent phenomenon in gliomas and occurs on the level of transcription involving epigenetic mechanism as well as on the level of mRNA splicing, which generates isoforms with compromised biological properties. PMID- 27256985 TI - Metal wires should not be abandoned inside implantable cardioverter defibrillators leads during heart transplantation! PMID- 27256983 TI - Interplay between chronic kidney disease (CKD) and upper tract urothelial carcinomas (UUC): foe or friend? AB - Although upper tract urothelial carcinomas (UUC) is curable through nephrectomy or nephroureterectomy, progression of chronic kidney disease (CKD) and CKD related mortality have been highlighted as clinical challenges in recent years owing to the loss of a large number of nephrons. While CKD can promote the development of UUC, other risk factors such as hypertension, diabetes mellitus, advanced age, and anemia can facilitate the progression of CKD. Conversely, CKD is especially prevalent in UUC patients. However, the relationship between CKD and UUC, mechanisms for CKD causing UUC, and gender disparity of UUC of CKD patients have so far not been well-reviewed. As UUC gradually grows, the cancer can be a physical obstacle in the urinary tract. It will cause an increased tract pressure, subsequently resulting in the dysfunction of both nephrons and kidney. At the molecular level, reduced level of oxidative stress was observed in female UUC patients. Furthermore, radical nephrectomy therapy for UUC patients accelerates the progress of chronic kidney dysfunction. Incidentally, the remedies for CKD containing aristolochic acid (AA) are carcinogenic. Our present review offers a comprehensive look at the relationship between CKD and UUC from multiple perspectives. Early and precise identification of progression of CKD and UUC will benefit the patients at high-risk of CKD or UUC, which will also be instructive in directing timely and effective therapeutic interventions whenever necessary. It may also shed light on unveiling the underlying mechanisms of carcinogenesis of UUC, preventing CKD progression, and prolonging the patients' overall survival. PMID- 27256984 TI - Autophagy gene expression profiling identifies a defective microtubule-associated protein light chain 3A mutant in cancer. AB - The cellular stress response autophagy has been implicated in various diseases including neuro-degeneration and cancer. The role of autophagy in cancer is not clearly understood and both tumour promoting and tumour suppressive effects of autophagy have been reported, which complicates the design of therapeutic strategies based on targeting the autophagy pathway. Here, we have systematically analyzed gene expression data for 47 autophagy genes for deletions, amplifications and mutations in various cancers. We found that several cancer types have frequent autophagy gene amplifications, whereas deletions are more frequent in prostate adenocarcinomas. Other cancer types such as glioblastoma and thyroid carcinoma show very few alterations in any of the 47 autophagy genes. Overall, individual autophagy core genes are altered at low frequency in cancer, suggesting that cancer cells require functional autophagy. Some autophagy genes show frequent single base mutations, such as members of the ULK family of protein kinases. Furthermore, we found hotspot mutations in the arginine-rich stretch in MAP1LC3A resulting in reduced cleavage of MAP1LC3A by ATG4B both in vitro and in vivo, suggesting a functional implication of this gene mutation in cancer development. PMID- 27256986 TI - Discovery of a Novel Microsomal Epoxide Hydrolase-Catalyzed Hydration of a Spiro Oxetane. AB - Oxetane moieties are increasingly being used by the pharmaceutical industry as building blocks in drug candidates because of their pronounced ability to improve physicochemical parameters and metabolic stability of drug candidates. The enzymes that catalyze the biotransformation of the oxetane moiety are, however, not well studied. The in vitro metabolism of a spiro oxetane-containing compound AZD1979 [(3-(4-(2-oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5 (4-ethoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone] was studied and one of its metabolites, M1, attracted our interest because its formation was NAD(P)H independent. The focus of this work was to elucidate the structure of M1 and to understand the mechanism(s) of its formation. We established that M1 was formed via hydration and ring opening of the oxetanyl moiety of AZD1979. Incubations of AZD1979 using various human liver subcellular fractions revealed that the hydration reaction leading to M1 occurred mainly in the microsomal fraction. The underlying mechanism as a hydration, rather than an oxidation reaction, was supported by the incorporation of (18)O from H2 (18)O into M1. Enzyme kinetics were performed probing the formation of M1 in human liver microsomes. The formation of M1 was substantially inhibited by progabide, a microsomal epoxide hydrolase inhibitor, but not by trans-4-[4-(1 adamantylcarbamoylamino)cyclohexyloxy]benzoic acid, a soluble epoxide hydrolase inhibitor. On the basis of these results, we propose that microsomal epoxide hydrolase catalyzes the formation of M1. The substrate specificity of microsomal epoxide hydrolase should therefore be expanded to include not only epoxides but also the oxetanyl ring system present in AZD1979. PMID- 27256988 TI - There's plenty of light at the bottom: statistics of photon penetration depth in random media. AB - We propose a comprehensive statistical approach describing the penetration depth of light in random media. The presented theory exploits the concept of probability density function f(z|rho, t) for the maximum depth reached by the photons that are eventually re-emitted from the surface of the medium at distance rho and time t. Analytical formulas for f, for the mean maximum depth and for the mean average depth reached by the detected photons at the surface of a diffusive slab are derived within the framework of the diffusion approximation to the radiative transfer equation, both in the time domain and the continuous wave domain. Validation of the theory by means of comparisons with Monte Carlo simulations is also presented. The results are of interest for many research fields such as biomedical optics, advanced microscopy and disordered photonics. PMID- 27256987 TI - Risk of recurrence of retinopathy of prematurity after initial intravitreal ranibizumab therapy. AB - We report our experience with the use of intravitreal ranibizumab for the treatment of retinopathy of prematurity (ROP). A retrospective review was performed on 138 consecutive infants screened at a single centre over 18 months. Intravitreal ranibizumab was offered in selected cases requiring treatment, such as aggressive posterior ROP or poor mydriasis. 2 eyes of 1 infant received intravitreal ranibizumab alone and 8 eyes of 5 infants received combined intravitreal ranibizumab and laser therapy. 3 out of 8 eyes treated initially with intravitreal ranibizumab monotherapy had persistent disease requiring laser therapy, and 3 out of 5 eyes with initial regression suffered disease recurrence at a mean of 7.6 weeks post-injection. 2 eyes treated first with laser followed by intravitreal ranibizumab had disease regression without recurrence. Our cohort demonstrate a significant rate of persistent disease and recurrence in ROP eyes treated initially with intravitreal ranibizumab monotherapy, which is greater and earlier than that reported for intravitreal bevacizumab in the BEAT-ROP study. Intravitreal ranibizumab may be useful as an initial treatment in selected cases of ROP when laser therapy as first line is suboptimal. However, close monitoring is important and adjunctive laser therapy may subsequently be needed in a majority of cases. PMID- 27256989 TI - Effects of ceftriaxone induced intestinal dysbacteriosis on lymphocytes in different tissues in mice. AB - The close relationship between intestinal microflora and immune system has been confirmed, stimulus from intestinal flora plays an important role in the development of the immune system and its dynamic balance. Current research is still inadequate to determine how local bacteria in gut influence the whole body. In this study, influence of ceftriaxone sodium induced intestinal dysbacteriosis on local and overall immune function was investigated. We found that the beneficial bacteria decreased significantly compared with control after oral administration of ceftriaxone; Moreover, the proportion of T cells are higher and B cells are lower in the dysbacteriosis mice, activation and proliferation of T and B cells was decreased significantly in gut-associated lymphoid tissues (GALTs), such as Peyer's patches (PPs) and mesenteric lymph nodes(MLNs)with ceftriaxone treatment; The secreted sIgA in intestinal was reduced in dysbacteriosis mice than that of control as well. The similar results above are also shown on the spleen. In addition, the delayed type hypersensitivity (DTH) reaction decreased in dysbacteriosis mice. The present data suggested that intestinal microflora had impact on immune system by influencing the proportion and function of lymphocytes in PPS-MLN-spleen. PMID- 27256990 TI - Improved Lower Urinary Tract Symptoms Associated With Testosterone Replacement Therapy in Japanese Men With Late-Onset Hypogonadism. AB - This study aimed to investigate the effects of testosterone replacement therapy (TRT) on lower urinary tract symptoms (LUTS) in men with late-onset hypogonadism (LOH) and to identify parameters predicting the efficacy of TRT in improving LUTS. This study included 60 consecutive Japanese men who were diagnosed with LOH and subsequently received TRT between January 2009 and December 2014. In this series, 250 mg of testosterone was injected intramuscularly every 3 or 4 weeks in all patients. The following parameters were retrospectively reviewed: body mass index (BMI), Aging Male Symptom (AMS) score, International Prostate Symptom Score (IPSS), International Index of Erectile Function-5 (IIEF-5) score, residual urine volume, prostate volume, serum levels of the prostate-specific antigen (PSA), and total- and free-testosterone levels before and 6 months after TRT. No significant differences were observed in BMI, residual urine volume, or prostate volume between surveys before and after TRT. The AMS score, IPSS, and IIEF-5 score were significantly improved and significant increases were noted in the serum levels of PSA and total- and free-testosterone levels after TRT. An analysis of IPSS subscores documented the significant improvement in storage symptom scores, but not in voiding symptom scores after TRT. Multivariate analyses of parameters assessed in this study identified the pretreatment AMS score, posttreatment IIEF 5 score, and prostate volume as independent predictors of improvements in IPSS following TRT. This study revealed that TRT appeared to have considerable therapeutic effects on LUTS, particularly on storage symptoms, in men with LOH. PMID- 27256991 TI - Method development to quantify Bv8 expression in circulating CD11b+ cells in patients with neovascular age-related macular degeneration (nvAMD) exhibiting Anti-VEGF refractoriness. AB - A subset of neovascular age-related macular degeneration (nvAMD) subjects appears to be refractory to the effects of anti-VEGF treatment and require frequent intravitreal injections. Prokineticin-2 (Bv8) expression in CD11b(+) cells has been linked to anti-VEGF response. We have developed a reproducible method to quantify gene expression in circulating CD11b + cells. Utilizing this method we tested the hypothesis that high Bv8 expression in circulating CD11b(+) cells is associated with anti-VEGF refractoriness in nvAMD patients. Two groups of nvAMD subjects undergoing treatment with anti-VEGF agents were recruited and classified as refractory or non-refractory to anti-VEGF treatment (n = 33 for each group). Two blood draws were obtained from each subject 1-9 months apart. Peripheral blood mononuclear cells (PBMCs) were isolated and CD11b(+) cells were purified via magnetic bead separation. RNA was purified, and relative expression of Bv8 among the subjects was compared via quantitative PCR analysis. Utilizing this approach no significant difference was detected in the mean LogRQ values between the first and second blood draws (t-test, p = 0.826) indicating low intra-patient variability and demonstrating good reproducibility of the assay. There was no significant difference in Bv8 expression between nvAMD subjects classified as refractory versus non-refractory. We were unable to find a correlation between Bv8 expression in CD11b + cells and anti-VEGF refractoriness in human nvAMD subjects. Relatively high expression in Bv8 in these subjects did not correlate with clinical treatment history, as measured by the frequency of injections. Utilizing this well characterized technique, studies are underway to examine alternative gene expression profiles in various circulating cell populations that may contribute to anti-VEGF refractoriness. PMID- 27256992 TI - Supplemental Parenteral Nutrition Is the Key to Prevent Energy Deficits in Critically Ill Patients. AB - This review emphasizes the role of a timely supplemental parenteral nutrition (PN) for critically ill patients. It contradicts the recommendations of current guidelines to avoid the use of PN, as it is associated with risk. Critical illness results in severe metabolic stress. During the early phase, inflammatory cytokines and mediators induce catabolism to meet the increased body energy demands by endogenous sources. This response is not suppressed by exogenous energy administration, and the early use of PN to reach the energy target leads to overfeeding. On the other hand, early and progressive enteral nutrition (EN) is less likely to cause overfeeding because of variable gastrointestinal tolerance, a factor frequently associated with significant energy deficit. Recent studies demonstrate that adequate feeding is beneficial during and after the intensive care unit (ICU) stay. Supplemental PN allows for timely adequate feeding, if sufficient precautions are taken to avoid overfeeding. Indirect calorimetry can precisely define the adequate energy prescription. Our pragmatic approach is to start early EN to progressively test the gut tolerance and add supplemental PN on day 3 or 4 after ICU admission, only if EN does not meet the measured energy target. We believe that supplemental PN plays a pivotal role in the achievement of adequate feeding in critically ill patients with intolerance to EN and does not cause harm if overfeeding is avoided by careful prescription, ideally based on energy expenditure measured by indirect calorimetry. PMID- 27256994 TI - Boy with central precocious puberty probably due to a peripheral cause. AB - A 61/2 years Indian boy was brought by his parents, who were anxious about the excessive increase in the size of the boy's phallus, from the age of 2 years. On physical examination, the child had a penis length greater than the 97th centile for age, a sexual maturity rating of gonads at stage 2 and pubic hair at stage 3, with height in the high normal range (90-97th centile). The bone age was 12 years. Laboratory evaluation showed pubertal levels of testosterone and pubertal gonadotropin response to stimulation, confirming central precocious puberty (CPP). Incidentally, the hormonal profile also suggested congenital adrenal hyperplasia (CAH). This case report depicts a case of CPP probably caused by CAH in boys, which is rare. PMID- 27256993 TI - Diagnosis of infant synostotic and nonsynostotic cranial deformities: a review for pediatricians. AB - OBJECTIVE: To review the current comprehensive care for nonsyndromic craniosynostosis and nonsynostotic cranial deformity and to offer an overall view of these craniofacial conditions. DATA SOURCE: The review was conducted in the PubMed, SciELO, and LILACS databases without time or language restrictions. Relevant articles were selected for the review. DATA SYNTHESIS: We included the anatomy and physiology of normal skull development of children, discussing nuances related to nomenclature, epidemiology, etiology, and treatment of the most common forms of nonsyndromic craniosynostosis. The clinical criteria for the differential diagnosis between positional deformities and nonsyndromic craniosynostosis were also discussed, giving to the pediatrician subsidies for a quick and safe clinical diagnosis. If positional deformity is accurately diagnosed, it can be treated successfully with behavior modification. Diagnostic doubts and craniosynostosis patients should be referred straightaway to a multidisciplinary craniofacial center. CONCLUSIONS: Pediatricians are in the forefront of the diagnosis of patients with cranial deformities. Thus, it is of paramount importance that they recognize subtle cranial deformities as it may be related to premature fusion of cranial sutures. PMID- 27256995 TI - Isolated bilateral inguinal lymphadenopathy in the absence of other symptoms, due to LGV in known HIV-positive MSM: is it more common than we think? AB - The current resurgence of lymphogranuloma venereum (LGV) has drawn most attention to its potential for causing proctitis; however, this case highlights the need for awareness of LGV as a cause of isolated painful bilateral inguinal lymphadenopathy in a high-risk population and the importance of routine screening for LGV. We describe a case of a 37-year-old HIV positive man, in the population of men who have sex with men (MSM) who presented with bilateral enlarged inguinal lymph nodes and no other symptoms or signs. Urine nucleic acid amplification test was positive for chlamydia LGV-specific DNA. Tests from other sites were negative. PMID- 27256996 TI - Complete response and long-term survival of leptomeningeal carcinomatosis from breast cancer with maintenance endocrine therapy. AB - Leptomeningeal carcinomatosis carries a poor prognosis in breast cancer. Treatment modalities are geared towards tumour molecular characteristics, as well as symptoms and patient performance status. It has previously been postulated that endocrine treatments used for the treatment of metastatic breast cancer do cross the blood-brain barrier and can achieve antineoplastic effects in the central nervous system. We report a case of metastatic breast cancer in a 65-year old woman who developed leptomeningeal carcinomatosis. She was initially treated with intrathecal methotrexate, which was stopped due to toxicity, followed by maintenance endocrine therapy. She achieved a sustained complete radiological and cerebrospinal fluid cytological response for over 9 years. She eventually passed away of ischaemic bowel unrelated to her cancer. PMID- 27256997 TI - Lethargy and vision loss: successful management of rhinocerebral mucormycosis. AB - Rhinocerebral mucormycosis (RCM) is an angioinvasive fungal infection most often caused by Rhizopus oryzae It is usually associated with an underlying risk factor and is associated with a poor prognosis. There are no consensus guidelines on the optimal management of this aggressive disease; most management decisions are based on case reports and expert opinion. We report a successfully managed case of RCM in an insulin-dependent diabetic, initially presenting with a change in mental status, rapidly progressing to complete right eye blindness and ophthalmoplegia and complicated by multiple cerebral infarctions and abscesses. We describe the diagnostic approach and various therapeutic interventions undertaken to successfully manage our patient. PMID- 27256998 TI - Dopa-responsive acute disseminated encephalomyelitis with marked atrophy of the striate body. PMID- 27256999 TI - Swept source: optical coherence tomography angiography features of choroidal osteoma with choroidal neovascular membrane. PMID- 27257000 TI - Diagnostic challenges in acromioclavicular septic arthritis. AB - A 69-year-old man with Klinefelter's syndrome presented with a painful shoulder and staphylococcal sepsis. He received intravenous antibiotics while investigations were performed to locate the source of infection. MRI demonstrated infection in the acromioclavicular joint (ACJ). The patient clinically improved and a further 5 weeks of oral antibiotics were given. He remained asymptomatic at 2-year follow-up. Although ACJ septic arthritis is rare, independent of immune competent status, a high index of suspicion is essential for prompt diagnosis. The condition presents additional diagnostic challenges due to unfamiliarity, the challenges of interpreting imaging, desire for radiological guided arthrocentesis and low volume aspirates. Overcoming these pitfalls is essential to avoid significant morbidity and mortality. PMID- 27257001 TI - Unusual case of acute neck pain: acute calcific longus colli tendinitis. AB - Acute calcific longus colli tendinitis (ACLCT), a very rare cause of severe neck pain, dysphagia and odynophagia, is often mistaken for other common causes of neck pain. However, prompt recognition of this uncommon presentation is important to prevent unnecessary medical and surgical intervention. A 46-year-old Caucasian man presented with a 1-day history of severe neck pain, headache and odynophagia. The patient was afebrile with stable vital signs, however, the laboratory data showed mildly elevated C reactive protein and erythrocyte sedimentation rate. The physical examination was remarkable for markedly reduced cervical range of motion. MRI revealed the pathognomonic findings of paravertebral oedema and calcification. The definitive diagnosis of ACLCT was made and the patient was successfully managed with a short course of oral steroid, benzodiazepine and aural acupuncture, with complete resolution of the condition within a week. PMID- 27257002 TI - Congenital absence of bilateral ICA: an unusual incidental finding in an adult male. PMID- 27257003 TI - Inspiratory muscle training to enhance recovery from mechanical ventilation: a randomised trial. AB - BACKGROUND: In patients who have been mechanically ventilated, inspiratory muscles remain weak and fatigable following ventilatory weaning, which may contribute to dyspnoea and limited functional recovery. Inspiratory muscle training may improve inspiratory muscle strength and endurance following weaning, potentially improving dyspnoea and quality of life in this patient group. METHODS: We conducted a randomised trial with assessor-blinding and intention-to treat analysis. Following 48 hours of successful weaning, 70 participants (mechanically ventilated >=7 days) were randomised to receive inspiratory muscle training once daily 5 days/week for 2 weeks in addition to usual care, or usual care (control). Primary endpoints were inspiratory muscle strength and fatigue resistance index (FRI) 2 weeks following enrolment. Secondary endpoints included dyspnoea, physical function and quality of life, post-intensive care length of stay and in-hospital mortality. RESULTS: 34 participants were randomly allocated to the training group and 36 to control. The training group demonstrated greater improvements in inspiratory strength (training: 17%, control: 6%, mean difference: 11%, p=0.02). There were no statistically significant differences in FRI (0.03 vs 0.02, p=0.81), physical function (0.25 vs 0.25, p=0.97) or dyspnoea (-0.5 vs 0.2, p=0.22). Improvement in quality of life was greater in the training group (14% vs 2%, mean difference 12%, p=0.03). In-hospital mortality was higher in the training group (4 vs 0, 12% vs 0%, p=0.051). CONCLUSIONS: Inspiratory muscle training following successful weaning increases inspiratory muscle strength and quality of life, but we cannot confidently rule out an associated increased risk of in-hospital mortality. TRIAL REGISTRATION NUMBER: ACTRN12610001089022, results. PMID- 27257005 TI - Population genetic analysis and bioclimatic modeling in Agave striata in the Chihuahuan Desert indicate higher genetic variation and lower differentiation in drier and more variable environments. AB - PREMISE OF THE STUDY: Is there an association between bioclimatic variables and genetic variation within species? This question can be approached by a detailed analysis of population genetics parameters along environmental gradients in recently originated species (so genetic drift does not further obscure the patterns). The genus Agave, with more than 200 recent species encompassing a diversity of morphologies and distributional patterns, is an adequate system for such analyses. We studied Agave striata, a widely distributed species from the Chihuahuan Desert, with a distinctive iteroparous reproductive ecology and two recognized subspecies with clear morphological differences. We used population genetic analyses along with bioclimatic studies to understand the effect of environment on the genetic variation and differentiation of this species. METHODS: We analyzed six populations of the subspecies A. striata subsp. striata, with a southern distribution, and six populations of A. striata subsp. falcata, with a northern distribution, using 48 ISSR loci and a total of 541 individuals (averaging 45 individuals per population). We assessed correlations between population genetics parameters (the levels of genetic variation and differentiation) and the bioclimatic variables of each population. We modeled each subspecies distribution and used linear correlations and multifactorial analysis of variance. KEY RESULTS: Genetic variation (measured as expected heterozygosity) increased at higher latitudes. Higher levels of genetic variation in populations were associated with a higher variation in environmental temperature and lower precipitation. Stronger population differentiation was associated with wetter and more variable precipitation in the southern distribution of the species. The two subspecies have genetic differences, which coincide with their climatic differences and potential distributions. CONCLUSIONS: Differences in genetic variation among populations and the genetic differentiation between A. striata subsp. striata and A. striata subsp. falcata is correlated with differences in environmental climatic variables along their distribution. We found two distinct gene pools that suggest active differentiation and perhaps incipient speciation. The detected association between genetic variation and environment variables indicates that climatic variables are playing an important role in the differentiation of A. striata. PMID- 27257004 TI - Interaction of vitamin E isoforms on asthma and allergic airway disease. AB - Prospective epidemiological studies, observational cross-sectional studies and some randomised prevention trials have demonstrated inconsistent findings of the impact of vitamin E on asthma risk. The goals of this study were to explore whether this differing association of vitamin E on asthma risk is due to an interaction of vitamin E isoforms. To address this question, in a population based asthma incidence study we assessed the interaction between the plasma concentrations of vitamin E isoforms alpha-tocopherol and gamma-tocopherol on asthma risk. Second, to understand the mechanisms of any interaction of these isoforms, we conducted experimental supplementation of alpha-tocopherol and gamma tocopherol isoforms in mice on the outcome of allergic airway inflammation. We found that in the highest gamma-tocopherol tertile, low levels of alpha tocopherol were associated with increased asthma risk, while highest tertile alpha-tocopherol levels trended to be protective. Similarly, in a mouse model of asthma, diet supplementation with alpha-tocopherol decreased lung inflammation in response to house dust mite (HDM) challenge. In contrast, diet supplementation with gamma-tocopherol increased lung inflammation in response to HDM. These human and animal studies provide evidence for the competing effects of the vitamin E isoforms, in physiological concentrations, on asthma and allergic airway disease. PMID- 27257006 TI - Abscission zone development in Setaria viridis and its domesticated relative, Setaria italica. AB - PREMISE OF THE STUDY: Development of an abscission zone (AZ) is needed for dispersal of seeds, and AZ loss was a critical early step in plant domestication. The AZ forms in different tissues in different species of plants, but whether the AZ is developmentally similar wherever it occurs is unknown. AZ development in Setaria viridis was studied as a representative of the previously uncharacterized subfamily Panicoideae. METHODS: One accession of the wild species S. viridis and two of its domesticate, S. italica, were studied. Strength of the AZ was measured with a force gauge. Anatomy of the AZ was studied throughout development using bright field and confocal microscopy. KEY RESULTS: The force required to remove a spikelet of S. viridis from the parent plant dropped steadily during development, whereas that required to remove spikelets of S. italica increased initially before stabilizing at a high level. Despite the clear difference in tensile strength of the AZ, anatomical differences between S. viridis and S. italica were subtle, and the position of the AZ was not easy to determine in cross sections of pedicel apices. Staining with DAPI showed that nuclei were present up to and presumably through abscission in S. viridis, and acridine orange staining showed much less lignification than in other cereals. CONCLUSIONS: The AZ in Setaria is developmentally and anatomically different from that characterized in rice, barley, and many eudicots. In particular, no set of small, densely cytoplasmic cells is obvious. This difference in anatomy could point to differential genetic control of the structure. PMID- 27257007 TI - Insect-induced plant phenotypes: Revealing mechanisms through comparative genomics of galling insects and their hosts. PMID- 27257008 TI - Antinociceptive Effects of Prim-O-Glucosylcimifugin in Inflammatory Nociception via Reducing Spinal COX-2. AB - We measured anti-nociceptive activity of prim-o-glucosylcimifugin (POG), a molecule from Saposhnikovia divaricate (Turcz) Schischk. Anti-nociceptive or anti inflammatory effects of POG on a formalin-induced tonic nociceptive response and a complete Freund's adjuvant (CFA) inoculation-induced rat arthritis pain model were studied. Single subcutaneous injections of POG produced potent anti nociception in both models that was comparable to indomethacin analgesia. Anti nociceptive activity of POG was dose-dependent, maximally reducing pain 56.6% with an ED50 of 1.6 mg. Rats given POG over time did not develop tolerance. POG also time-dependently reduced serum TNFalpha, IL-1beta and IL-6 in arthritic rats and both POG and indomethacin reduced spinal prostaglandin E2 (PGE2). Like indomethacin which inhibits cyclooxygenase-2 (COX-2) activity, POG dose dependently decreased spinal COX-2 content in arthritic rats. Additionally, POG, and its metabolite cimifugin, downregulated COX-2 expression in vitro. Thus, POG produced potent anti-nociception by downregulating spinal COX-2 expression. PMID- 27257009 TI - Salvia miltiorrhiza Bunge Blocks Ethanol-Induced Synaptic Dysfunction through Regulation of NMDA Receptor-Dependent Synaptic Transmission. AB - Consumption of high doses of ethanol can lead to amnesia, which often manifests as a blackout. These blackouts experienced by ethanol consumers may be a major cause of the social problems associated with excess ethanol consumption. However, there is currently no established treatment for preventing these ethanol-induced blackouts. In this study, we tested the ethanol extract of the roots of Salvia miltiorrhiza (SM) for its ability to mitigate ethanol-induced behavioral and synaptic deficits. To test behavioral deficits, an object recognition test was conducted in mouse. In this test, ethanol (1 g/kg, i.p.) impaired object recognition memory, but SM (200 mg/kg) prevented this impairment. To evaluate synaptic deficits, NMDA receptor-mediated excitatory postsynaptic potential (EPSP) and long-term potentiation (LTP) in the mouse hippocampal slices were tested, as they are known to be vulnerable to ethanol and are associated with ethanol-induced amnesia. SM (10 and 100 MUg/ml) significantly ameliorated ethanol induced long-term potentiation and NMDA receptor-mediated EPSP deficits in the hippocampal slices. Therefore, these results suggest that SM prevents ethanol induced amnesia by protecting the hippocampus from NMDA receptor-mediated synaptic transmission and synaptic plasticity deficits induced by ethanol. PMID- 27257010 TI - Inhibitory Effects of Norwogonin, Oroxylin A, and Mosloflavone on Enterovirus 71. AB - Severe complications associated with EV71 infections are a common cause of neonatal death. Lack of effective therapeutic agents for these infections underlines the importance of research for the development of new antiviral compounds. In the present study, the anti-EV71 activity of norwogonin, oroxylin A, and mosloflavone from Scutellaria baicalensis Georgi was evaluated using a cytopathic effect (CPE) reduction method, which demonstrated that all three compounds possessed strong anti-EV71 activity and decreased the formation of visible CPEs. Norwogonin, oroxylin A, and mosloflavone also inhibited virus replication during the initial stage of virus infection, and they inhibited viral VP2 protein expression, thereby inhibiting viral capsid protein synthesis. However, ribavirin has a relatively weaker efficacy compared to the other drugs. Therefore, these findings provide important information that will aid in the utilization of norwogonin, oroxylin A, and mosloflavone for EV71 treatment. PMID- 27257011 TI - Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma Cells. AB - Shikonin, which derives from Lithospermum erythrorhizon, has been traditionally used against a variety of diseases, including cancer, in Eastern Asia. Here we determined that shikonin inhibits proliferation of gastric cancer cells by inducing apoptosis. Shikonin's biological activity was validated by observing cell viability, caspase 3 activity, reactive oxygen species (ROS) generation, and apoptotic marker expressions in AGS stomach cancer cells. The concentration range of shikonin was 35-250 nM with the incubation time of 6 h. Protein levels of Nrf2 and p53 were evaluated by western blotting and confirmed by real-time PCR. Our results revealed that shikonin induced the generation of ROS as well as caspase 3 dependent apoptosis. c-Jun-N-terminal kinases (JNK) activity was significantly elevated in shikonin-treated cells, thereby linking JNK to apoptosis. Furthermore, our results revealed that shikonin induced p53 expression but repressed Nrf2 expression. Moreover, our results suggested that there may be a co regulation between p53 and Nrf2, in which transfection with siNrf2 induced the p53 expression. We demonstrated for the first time that shikonin activated cell apoptosis in AGS cells via caspase 3- and JNK-dependent pathways, as well as through the p53-Nrf2 mediated signal pathway. Our study validates in partly the contribution of shikonin as a new therapeutic approaches/ agent for cancer chemotherapy. PMID- 27257012 TI - Baicalein Protects Human Skin Cells against Ultraviolet B-Induced Oxidative Stress. AB - Baicalein (5,6,7-trihydroxy-2-phenyl-chromen-4-one) is a flavone, a type of flavonoid, originally isolated from the roots of Scutellaria baicalensis. This study evaluated the protective effects of baicalein against oxidative damage mediated apoptosis induced by ultraviolet B (UVB) radiation in a human keratinocyte cell line (HaCaT). Baicalein absorbed light within the wavelength range of UVB. In addition, baicalein decreased the level of intracellular reactive oxygen species (ROS) in response to UVB radiation. Baicalein protected cells against UVB radiation-induced DNA breaks, 8-isoprostane generation and protein modification in HaCaT cells. Furthermore, baicalein suppressed the apoptotic cell death by UVB radiation. These findings suggest that baicalein protected HaCaT cells against UVB radiation-induced cell damage and apoptosis by absorbing UVB radiation and scavenging ROS. PMID- 27257014 TI - DTB Select: 6 | June 2016. AB - EMA reviews risk of pneumonia with inhaled corticosteroids for COPD ? Updated USA guidance on opioids for chronic pain ? Tackling high-risk prescribing ? Influencing antibiotic prescribing in primary care ? Commuting, BMI and obesity ? Cardiovascular effects of antidepressants ? PPI use and dementia ? Older people and risk of drug interactions. PMID- 27257013 TI - Quercetin-3-O-beta-D-Glucuronide Suppresses Lipopolysaccharide-Induced JNK and ERK Phosphorylation in LPS-Challenged RAW264.7 Cells. AB - Quercetin, a flavonol, has been reported to exhibit a wide range of biological properties including anti-oxidant and anti-inflammatory activities. However, pharmacological properties of quercetin-3-O-beta-D-glucuronide (QG), a glycoside derivative of quercetin, have not been extensively examined. The objective of this study is to elucidate the anti-inflammatory property and underlying mechanism of QG in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells in comparison with quercetin. QG significantly suppressed LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and PGE2, and pro-inflammatory protein expressions of iNOS and COX-2. To elucidate the underlying mechanism of the anti-inflammatory property of QG, involvement of MAPK signaling pathways was examined. QG significantly attenuated LPS-induced activation of JNK and ERK in concentration-dependent manners with a negligible effect on p38. In conclusion, the present study demonstrates QG exerts anti-inflammatory activity through the suppression of JNK and ERK signaling pathways in LPS-challenged RAW264.7 macrophage cells. PMID- 27257015 TI - Is Interarterial Course a Requisite for Ischemia in Anomalous Origin of Coronary Arteries? AB - Anomalous origin of the left main coronary artery from the noncoronary sinus (LCANS) is a rare variant of anomalous aortic origin of a coronary artery that is not characterized by an interarterial course. Despite the absence of an interarterial course, there are rare reports of LCANS presenting with sudden death, life-threatening arrhythmia, exercise-induced myocardial ischemia, premature ventricular contractions, and syncope. We report a patient with LCANS presenting with acute myocardial infarction who recovered completely with emergent surgical unroofing of the coronary artery. PMID- 27257016 TI - The Prevalence of CKD in Rural Canadian Indigenous Peoples: Results From the First Nations Community Based Screening to Improve Kidney Health and Prevent Dialysis (FINISHED) Screen, Triage, and Treat Program. AB - BACKGROUND: Indigenous Canadians have high rates of risk factors for chronic kidney disease (CKD), in particular diabetes. Furthermore, they have increased rates of complications associated with CKD, such as kidney failure and vascular disease. Our objective was to describe the prevalence of CKD in this population. STUDY DESIGN: Cross-sectional cohort. SETTING & PARTICIPANTS: Indigenous (First Nations) Canadians 18 years or older screened as part of the First Nations Community Based Screening to Improve Kidney Health and Prevent Dialysis (FINISHED) project, an initiative completed in 2015 that accomplished community wide screening in 11 rural communities in Manitoba, Canada. PREDICTORS: Indigenous ethnicity and geographic location (communities accessible by road compared with those accessible only by air). OUTCOME: Prevalence of CKD, presumed based on a single ascertainment of urine albumin-creatinine ratio (UACR) >= 30mg/g and/or estimated glomerular filtration rate (eGFR)<60mL/min/1.73m(2). MEASUREMENTS: Kidney function measured by eGFR (CKD-EPI creatinine equation) and UACR. RESULTS: 1,346 adults were screened; 25.5% had CKD, defined as UACR>=30mg/g or eGFR<60mL/min/1.73m(2). Communities accessible by road had a lower prevalence of CKD (17.6%) than more remote communities accessible only by air (34.4%). Of those screened, 3.3% had reduced kidney function (defined as eGFR<60mL/min/1.73m(2)). Severely increased albuminuria was present in 5.0% of those screened. LIMITATIONS: Presumption of chronicity based on a single ascertainment. There is a possibility of sampling bias, the net direction of which is uncertain. CONCLUSIONS: We found a 2-fold higher prevalence of CKD in indigenous Canadians in comparison to the general population and a prevalence of severely increased albuminuria that was 5-fold higher. This is comparable to patients with diabetes and/or hypertension. Public health strategies to screen, triage, and treat all Canadian indigenous peoples with CKD should be considered. PMID- 27257018 TI - Securing a future for responsible neuromodulation in children: The importance of maintaining a broad clinical gaze. AB - AIM: This perspective paper provides an overview of several key tensions and challenges within the social context of neuromodulation, and it suggests a means of securing the future of paediatric neuromodulation in light of these. RESULTS: Tensions and challenges relate to: the considerable clinical and economic need for new therapies to manage neurological diseases; significant commercial involvement in the field; funding pressures; public perceptions (particularly unrealistic expectations); and the emerging Responsible Research and Innovation initiative. This paper argues that managing these challenges and tensions requires that clinicians working within the field adopt what could be called a broad clinical gaze. This paper will define the broad clinical gaze, and it will propose several ways in which a broad clinical gaze can be - and indeed is being operationalised in recent advances in neuromodulation in children. These include the use of multidisciplinary and interdisciplinary clinical team structures, the adoption of clinical assessment tools that capture day-to-day functionality, and the use of patient registries. CONCLUSION: By adopting a broad clinical gaze, clinicians and investigators can ensure that the field as a whole can responsibly and ethically deliver on its significant clinical potential. PMID- 27257019 TI - Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages. AB - Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies. PMID- 27257017 TI - CNV analysis in Chinese children of mental retardation highlights a sex differentiation in parental contribution to de novo and inherited mutational burdens. AB - Rare copy number variations (CNVs) are a known genetic etiology in neurodevelopmental disorders (NDD). Comprehensive CNV analysis was performed in 287 Chinese children with mental retardation and/or development delay (MR/DD) and their unaffected parents. When compared with 5,866 ancestry-matched controls, 11~12% more MR/DD children carried rare and large CNVs. The increased CNV burden in MR/DD was predominantly due to de novo CNVs, the majority of which (62%) arose in the paternal germline. We observed a 2~3 fold increase of large CNV burden in the mothers of affected children. By implementing an evidence-based review approach, pathogenic structural variants were identified in 14.3% patients and 2.4% parents, respectively. Pathogenic CNVs in parents were all carried by mothers. The maternal transmission bias of deleterious CNVs was further replicated in a published dataset. Our study confirms the pathogenic role of rare CNVs in MR/DD, and provides additional evidence to evaluate the dosage sensitivity of some candidate genes. It also supports a population model of MR/DD that spontaneous mutations in males' germline are major contributor to the de novo mutational burden in offspring, with higher penetrance in male than female; unaffected carriers of causative mutations, mostly females, then contribute to the inherited mutational burden. PMID- 27257020 TI - Engineering skyrmions in transition-metal multilayers for spintronics. AB - Magnetic skyrmions are localized, topologically protected spin structures that have been proposed for storing or processing information due to their intriguing dynamical and transport properties. Important in terms of applications is the recent discovery of interface stabilized skyrmions as evidenced in ultra-thin transition-metal films. However, so far only skyrmions at interfaces with a single atomic layer of a magnetic material were reported, which greatly limits their potential for application in devices. Here we predict the emergence of skyrmions in [4d/Fe2/5d]n multilayers, that is, structures composed of Fe biatomic layers sandwiched between 4d and 5d transition-metal layers. In these composite structures, the exchange and the Dzyaloshinskii-Moriya interactions that control skyrmion formation can be tuned separately by the two interfaces. This allows engineering skyrmions as shown based on density functional theory and spin dynamics simulations. PMID- 27257021 TI - Review: Roles for astrocytes in epilepsy: insights from malformations of cortical development. AB - Malformations of cortical development (MCDs), such as cortical dysplasia and tuberous sclerosis complex, are common causes of intractable epilepsy, especially in paediatric patients. Recently, mounting evidence points to a common pathology of these disorders. Hyperactivation of mammalian target of rapamycin (mTOR) has been proposed as a central mechanism in most, if not all, MCDs. The transition from mTOR hyperactivation and cellular abnormalities to large-scale functional changes and seizure is, however, not fully understood. In this article we set out to review currently available information regarding MCD pathology, focusing on glial cells - especially astrocytes - and their interactions with the brain vascular system. A large body of evidence points to these elements as potential targets in MCD. Here, we attempt to provide a review of this evidence and propose some hypotheses regarding the possible chain of events linking primary glial dysfunction and epilepsy. We focus on extracellular matrix remodelling, blood brain barrier leakage and failure of astrocyte-dependent removal of extracellular debris. We posit that the failure of these systems results in a chronically pro inflammatory environment, maintaining local astrocytes in a state of gliosis, with increased susceptibility to seizures as a consequence. PMID- 27257022 TI - Platelet reactivity over time in coronary artery disease patients treated with a bioabsorbable everolimus-eluting scaffold. AB - Everolimus-eluting bioabsorbable scaffolds (BVSs) have exhibited similar long term clinical outcomes compared to its everolimus-eluting metallic counterparts. However, reports from earlier studies have shown a signal for an increased rate of stent thrombosis. The aim of the current investigation is to describe the platelet reactivity profiles over time in patients treated with everolimus eluting BVS in comparison to everolimus-eluting metallic stents. This is a pilot study in which patients on aspirin and clopidogrel with at least 1 everolimus eluting BVS were included (n = 24). Patients with at least 1 everolimus-eluting metallic stent implanted were included as control group (n = 25). Blood samples were taken at time of discharge and at 3- and 6-month follow-up. Platelet function tests included VerifyNow (VN-P2Y12), multiplate aggregometry (MEA), and light transmission aggregometry (LTA). There was no difference in platelet reactivity at discharge, 3- and 6-month visits (unadjusted p = 0.733 and p = 0.582; p = 0.432 and p = 0.899 after adjusting for discharge value platelet reactivity0, respectively) using VN-P2Y12. Similar findings were observed with LTA. However, patients with BVS showed significantly higher platelet reactivity than patients with metallic stents at 3 and 6 months in the crude analysis (p = 0.003) and after adjusting for discharge value (p = 0.013) measured with ADP-MEA. There were no differences in platelet reactivity mediated by the T * A2 pathway between both groups. Finally, there is no statistical difference in high on clopidogrel platelet reactivity (HPR) rate between both groups. The results of this pilot study suggest that BVS might have different platelet reactivity profiles, and warrants further investigation in dedicated clinical studies. PMID- 27257024 TI - Dose Schedules Inspired by Evolutionary Concepts Lengthen Progression-Free Survival in Mice. PMID- 27257023 TI - Clinical Model for Predicting Hepatocellular Carcinomas in Patients with Post Sustained Virologic Responses of Chronic Hepatitis C: A Case Control Study. AB - Background/Aims: No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). Methods: We performed a case control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. Results: In the multivariate model, an initial diagnosis of compensated cirrhosis and post SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p<0.001) and 1.3-fold (95% CI, 1.1 to 1.7; p=0.004) increases in the risk of HCC after SVR, respectively. A predictive model based on an initial diagnosis of compensated cirrhosis (yes, +1; no, 0) and post-SVR albumin <=36.0 g/L (yes, +1; not, 0) predicted the occurrence of HCC after SVR with a cutoff value of >0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. Conclusions: An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of <=36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC. PMID- 27257026 TI - Shock Therapy for Late-Stage Pancreatic Cancer Gets Closer Look. PMID- 27257027 TI - Continuing To Smoke After Breast Cancer Diagnosis Lowers Survival Rate. PMID- 27257028 TI - Heterogeneous and Rare: Toward Histology-Specific Treatment of Soft-Tissue Sarcoma. PMID- 27257030 TI - Needle-free jet injection of hyaluronic acid improves skin remodeling in a mouse model. AB - PURPOSE: The purpose of this study was to improve methods of jet injection using a mouse model. We investigated the mechanism of action, efficacy, and safety of the pneumatic device using injection of hyaluronic acid (HA) solution into a mouse model. METHODS: We evaluated the efficacy and safety of an INNOJECTORTM pneumatic device that pneumatically accelerates a jet of HA solution under high pressure into the dermis of mouse skin. We examined the treatment effects using skin hybrid model jet dispersion experiments, photographic images, microscopy, and histological analyses. RESULTS: Use of the INNOJECTORTM successfully increased dermal thickness and collagen synthesis in our mouse model. Jet dispersion experiments were performed using agarose gels and a polyacrylamide gel model to understand the dependence of jet penetration on jet power. The mechanisms by which pneumatic injection using HA solution exerts its effects may involve increased dermal thickening, triggering of a wound healing process, and activation of vimentin and collagen synthesis. CONCLUSIONS: Collagen synthesis and increased dermal thickening were successfully achieved in our mouse model using the INNOJECTORTM. Pneumatic injection of HA under high pressure provides a safe and effective method for improving the appearance of mouse skin. Our findings indicate that use of the INNOJECTORTM may induce efficient collagen remodeling with subsequent marked dermal layer thickening by targeting vimentin. PMID- 27257031 TI - Tsukamurella serpentis sp. nov., isolated from the oral cavity of Chinese cobras (Naja atra). AB - Two bacterial strains, HKU54T and HKU55, were isolated from the oral cavity of two Chinese cobras (Naja atra) in Hong Kong. 16S rRNA gene sequence analysis revealed 100 % sequence identity between HKU54T and HKU55, and the two strains shared 99.0 % sequence identities with Tsukamurella inchonensis ATCC 700082T. The two strains had unique biochemical profiles distinguishable from closely related species of the genus Tsukamurella. DNA-DNA hybridization confirmed that they belonged to the same species (>=92.1+/-7.9 % DNA-DNA relatedness) but were distinct from all other known species of the genus Tsukamurella (<=52.6+/-5.3 % DNA-DNA relatedness). Chemotaxonomic and morphological analyses of the two strains also demonstrated results consistent with their classification in the genus Tsukamurella. The DNA G+C contents of strains HKU54T and HKU55 were 69.2+/ 1.5 mol% and 69.2+/-1.3 mol% (mean+/-sd; n=3) respectively. A novel species, Tsukamurella serpentis sp. nov., is proposed to accommodate strains HKU54T and HKU55, with HKU54T (=JCM 31017T=DSM 100915T) designated as the type strain. PMID- 27257032 TI - Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats. AB - Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5 hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs. PMID- 27257033 TI - Validation of a first-trimester screening model for pre-eclampsia in an unselected population. AB - OBJECTIVE: To validate the performance of a previously constructed first trimester predictive model for pre-eclampsia (PE) in routine care of an unselected population. METHODS: A validation cohort of 4621 consecutive women attending their routine first-trimester ultrasound examination was used to test a prediction model for PE that had been developed previously in 5170 women. The prediction model included maternal factors, uterine artery Doppler, blood pressure and pregnancy-associated plasma protein-A. Model performance was evaluated using receiver-operating characteristics (ROC) curve analysis and ROC curves from both cohorts were compared unpaired. RESULTS: Among the 4203 women included in the final analysis, 169 (4.0%) developed PE, including 141 (3.4%) cases of late-onset PE and 28 (0.7%) cases of early-onset PE. For early-onset PE, the model showed an area under the ROC curve of 0.94 (95% CI, 0.88-0.99), which did not differ significantly (P = 0.37) from that obtained in the construction cohort (0.88 (95% CI, 0.78-0.99)). For late-onset PE, the final model showed an area under the ROC curve of 0.72 (95% CI, 0.66-0.77), which did not differ significantly (P = 0.49) from that obtained in the construction cohort (0.75 (95% CI, 0.67-0.82)). CONCLUSION: The prediction model for PE achieved a similar performance to that obtained in the construction cohort when tested on a subsequent cohort of women, confirming its validity as a predictive model for PE. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27257034 TI - Effect of chromatic filters on visual performance in individuals with mild traumatic brain injury (mTBI): A pilot study. AB - PURPOSE: Spectral filters have been used clinically in patients with mild traumatic brain injury (mTBI). However, they have not been formally assessed using objective techniques in this population. Thus, the aim of the present pilot study was to determine the effect of spectral filters on reading performance and visuo-cortical responsivity in adults with mTBI. METHODS: 12 adults with mTBI/concussion were tested. All reported photosensitivity and reading problems. They were compared to 12 visually-normal, asymptomatic adults. There were several test conditions: three luminance-matched control filters (gray neutral density, blue, and red), the patient-selected 'precision tint lens' that provided the most comfort and clarity of text using the Intuitive Colorimeter System, and baseline without any filters. The Visagraph was used to assess reading eye movements and reading speed objectively with each filter. In addition, both the amplitude and latency of the visual-evoked potential (VEP) were assessed with the same filters. RESULTS: There were few significant group differences in either the reading related parameters or VEP latency for any of the test filter conditions. Subjective improvements were noted in most with mTBI (11/12). CONCLUSIONS: The majority of patients with mTBI chose a tinted filter that resulted in increased visual comfort. While significant findings based on the objective testing were found for some conditions, the subjective results suggest that precision tints should be considered as an adjunctive treatment in patients with mTBI and photosensitivity. PMID- 27257035 TI - Extreme response style as a cultural response to climato-economic deprivation. AB - We investigated the effects of climato-economic harshness on extreme response style. Climato-economic theorising postulates that a more threatening climate in poorer countries, in contrast to countries with a more comforting climate and richer countries with a more challenging climate, triggers intolerance of ambiguity and uncertainty avoidance inherent to conservatism, in-group favouritism and autocracy. Scores of extreme response style at country level, a proxy of this cluster of cultural characteristics, were extracted from students' responses in the Programme for International Student Assessment to test the hypothesis. In a series of hierarchical regression analysis across 64 countries, cold demands, heat demands and GDP per capita showed a highly significant interaction effect on extreme response style, predicting in total 30.7% of the variance. Extreme response style was highest in poorer countries with higher climatic demands, and lowest in richer countries with lower climate demands. Implications are discussed. PMID- 27257036 TI - Cross-Modal Correspondence Among Vision, Audition, and Touch in Natural Objects: An Investigation of the Perceptual Properties of Wood. AB - Certain systematic relationships are often assumed between information conveyed from multiple sensory modalities; for instance, a small figure and a high pitch may be perceived as more harmonious. This phenomenon, termed cross-modal correspondence, may result from correlations between multi-sensory signals learned in daily experience of the natural environment. If so, we would observe cross-modal correspondences not only in the perception of artificial stimuli but also in perception of natural objects. To test this hypothesis, we reanalyzed data collected previously in our laboratory examining perceptions of the material properties of wood using vision, audition, and touch. We compared participant evaluations of three perceptual properties (surface brightness, sharpness of sound, and smoothness) of the wood blocks obtained separately via vision, audition, and touch. Significant positive correlations were identified for all properties in the audition-touch comparison, and for two of the three properties regarding in the vision-touch comparison. By contrast, no properties exhibited significant positive correlations in the vision-audition comparison. These results suggest that we learn correlations between multi-sensory signals through experience; however, the strength of this statistical learning is apparently dependent on the particular combination of sensory modalities involved. PMID- 27257037 TI - The Effect of Obesity on Perioperative Outcomes Following Percutaneous Nephrolithotomy. AB - OBJECTIVES: To test if obesity predisposes to higher rates of adverse outcomes after percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Within the Nationwide Inpatient Sample (NIS), we identified patients treated with PCNL between 1998 and 2010 for kidney stones. We examined the temporal trends in PCNL use and charges among obese and nonobese patients. We then tested the effect of obesity on perioperative complications, transfusions, length of stay (LOS), and total hospital charges (THCs). LOS and THCs were defined as a continuous variable and were also dichotomized according to the 75th percentile into prolonged LOS (pLOS) and increased THCs (iTHCs). Then, multivariable models were fitted. RESULTS: Overall, a weighted sample of 90,529 individuals treated with PCNL between 1998 and 2010 was examined. Of those patients, 9300 were obese (10.3%). The proportion of PCNLs performed in obese patients increased throughout the years from 7.4% to 16.7% (p < 0.001). Overall complication rates were 21.6% vs 22.0% (p = 0.3) and transfusion rates were 4.3% vs 4.0% (p = 0.1) for obese and nonobese patients, respectively. Obese patients had fewer genitourinary complications (13.4% vs 15.0%, p < 0.001), but had higher rates of sepsis (1.7% vs 1.3%, p = 0.009) as well as respiratory (3.0% vs 2.5%, p = 0.002) and vascular complications (0.3% vs 0.2%, p = 0.007). Conversely, pLOS (20.9% vs 18.8%, p < 0.001) and iTHCs (30.8% vs 24.4%, p < 0.001) were more frequently recorded in obese patients. In multivariable analyses, obesity was neither associated with higher rates of overall complications (odds ratio [OR], p = 0.3) nor with higher rates of transfusions (p = 0.3). However, obesity was associated with pLOS (OR: 1.21, p = 0.002) as well as iTHCs (OR: 1.17, p = 0.002). CONCLUSIONS: PCNL in obese patients did not result in higher rates of individual complications or transfusions. However, it resulted in higher rates of pLOS and iTHCs. PMID- 27257038 TI - Development of a drug-in-adhesive patch combining ion pair and chemical enhancer strategy for transdermal delivery of zaltoprofen: pharmacokinetic, pharmacodynamic and in vitro/in vivo correlation evaluation. AB - The aim of the study was to develop a drug-in-adhesive patch system for transdermal delivery of zaltoprofen (ZAL). The formulation was designed in combination with the ion pair and chemical enhancer strategy. Seven organic amines were chosen as counter ions, and the prepared ion pairs were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The in vivo pharmacokinetic performance of ZAL was studied on rabbits following transdermal and intravenous administration. A deconvolution method was applied to determine the correlation between the in vitro permeation and the in vivo absorption. Acetic acid-induced writhing response was conducted on mice to evaluate the analgesic effect. In vitro permeation results showed that both ion pairs and chemical enhancers were effective in modulating ZAL skin permeation from patches. The enhancement ratio was negatively correlated to the polar surface area (PSA) of counter ions, and was positively correlated to the octanol-water partition coefficient (log Ko/w) of chemical enhancers, respectively. The optimized formulation contained 10% (w/w) ZAL-triethylamine and 10% (w/w) isopropyl myristate, with DURO-TAK(r) 87-4098 as the pressure sensitive adhesive matrix. Furthermore, the in vitro permeation data were well correlated with the in vivo absorption data. The analgesic effect of the optimized patch was comparable to the commercial indometacin plasters. In conclusion, it was feasible for transdermal delivery of ZAL by the synergistic action of ion pair and chemical enhancer, and the in vitro permeation data were indicative of the in vivo performance for the developed patches. PMID- 27257039 TI - The neuropilin-1 receptor mediates enhanced tumor delivery of H2K polyplexes. AB - BACKGROUND: Promising plasmid-based treatments have limited value without an effective delivery system. Recently, the linear H2K with a repeating -KHHK- pattern was determined to be an effective plasmid carrier to tumor xenografts in vivo. Although unpacking of the H2K polyplex within the tumor may have a role, the mechanism for the enhanced efficacy remains unclear. METHODS: After solid phase synthesis of linear and branched histidine-lysine (HK) peptide carriers of plasmids, the peptides were compared for their ability to lyse endosomes with a red blood cell model and to transfect MDA-MB-435 xenografts in the presence or absence of neuropilin-1 receptor (NRP-1) antibodies. To examine stability, polyplexes were incubated with trypsin or NaCl and then analyzed by electrophoresis. RESULTS: After screening peptides with a model for endosomal lysis at two pHs, the 33-mer H3K peptide lysed red blood cells effectively at the lower pH. Combining H3K and H2K peptides as carriers of plasmids expressing luciferase were more effective than H2K alone. Based on the repeating -KHHK- sequences of H2K, we studied whether the widespread gene expression in the tumor may be mediated by NRP-1. By blocking NRP-1 in tumor-bearing mice, luciferase activity in tumors delivered by HK polyplexes was reduced by 96%, whereas activity in normal tissues was minimally reduced. CONCLUSIONS: Combining an endosomolytic peptide, H3K, with H2K polyplexes as a carrier further enhanced transfection in vivo. Moreover, the widespread distribution of H2K polyplexes is mediated by NRP-1, suggesting that transcytosis of these polyplexes through the tumor endothelium may lead to efficient transfection. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27257041 TI - Does the distance between tumor and margin in radical prostatectomy specimens correlate with prognosis: relation to tumor location. AB - The posterior half of the prostate has a smooth well-defined edge unlike anteriorly. Often, tumor extends close to the posterior margin, where it is controversial whether pathologists should measure the distance between the tumor and the margin. There are no published data regarding the significance of a close margin factoring in the anatomical location within the radical prostatectomy (RP). We identified 158 RPs with 39 anterior-predominant carcinomas and 119 cases with posterior-predominant cancer. Distances between the tumor and inked margin were measured with an ocular micrometer. Eighty-seven cases had no progression with a minimum 6-year follow-up (median, 8; range, 6-9). Eighteen cases had progression with a median time to progression of 2 years with all men progressing within 6 years after RP. There was no statistically significant difference in the risk of progression relative to distance of tumor to the posterior margin (P=.09). The mean distance of tumor to the anterior margin for the cases that progressed was 0.6 mm (median, 0.5 mm; range, 0.05-1.18) compared to 1.9 mm (median, 1.1; range, 0.02-4) for the cases that did not progress (P=.02). Of 7 cases with anterior-predominant tumors that progressed, 5 had tumor located less than 1 mm from the anterior margin. In conclusion, if cancer is present less than 1 mm from the anterior margin, there is an increased tendency to recur, and this finding should be included in pathology reports. However, close margins posteriorly are not clinically significant and should not be reported. PMID- 27257040 TI - Glomerular C3d as a novel prognostic marker for renal vasculitis. AB - Pauci-immune necrotizing crescentic glomerulonephritis is the histologic substrate of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Several studies in animal models have demonstrated the crucial role of complement activation in the pathogenesis of ANCA-associated vasculitis, but only small series have analyzed the prognostic implications of complement glomerular deposits. This study aimed to assess the clinical and prognostic implications of C3d- and C4d-positive glomerular staining in renal vasculitis. Eighty-five patients with a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis were included in the study. C3d and C4d were analyzed by immunohistochemical staining using a polyclonal antibody. The primary predictors were glomerular C3d- and C4d-positive staining. The primary end point was the cumulative percentage of patients who developed end-stage renal disease. Glomerular staining for C3d and C4d was observed in 42 (49.4%) of 85 biopsies and 38 (44.7%) of 85 biopsies, respectively. C3d-positive staining was associated with the severity of renal impairment and with a lower response rate to treatment (P=.003 and P=.04, respectively). Renal survival at 2 and 5 years was 60.9% and 51.8% in C3d-positive patients compared with 87.7% and 78.9% in C3d-negative patients (P=.04). C4d-positive staining did not show any impact in renal outcome. When adjusted by renal function and other histologic parameters, C3d staining remained as an independent predictor for renal survival (hazard ratio, 2.5; 95% confidence interval, 1.1-5.7; P=.03). Therefore, this study demonstrates that C3d positive glomerular staining is an independent risk factor for the development of end-stage renal disease in ANCA-associated renal vasculitis. PMID- 27257042 TI - Burkitt lymphoma presenting as a mass in the thyroid gland: a clinicopathologic study of 7 cases and review of the literature. AB - Burkitt lymphoma presenting in the thyroid gland is rare, and only a few cases have been reported. We retrospectively reviewed 7 patients diagnosed with Burkitt lymphoma of the thyroid gland between 2000 and 2015. There were 4 men and 3 women with a median age of 41 years (range, 19-49 years). All patients presented with a rapidly growing neck mass associated with upper airway compression in 5 (71%) patients. Two patients presented with localized (stage I/II) and 5 patients with disseminated (stage III/IV) disease. All cases showed morphologic and immunophenotypic features of Burkitt lymphoma with MYC rearrangement in all 5 cases tested. One case showed evidence of concurrent Hashimoto thyroiditis. Six of 7 patients were treated primarily with rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone. One patient was treated primarily with dose-adjusted rituximab, etoposide, prednisolone, vincristine, and cyclophosphamide. At the end of the study period, 5 patients were alive: 4 in complete remission and 1 with persistent disease. Two patients died with persistent disease (median follow-up, 25 months; range, 12-361 months). We conclude that Burkitt lymphoma of the thyroid gland shows clinicopathologic features similar to sporadic Burkitt lymphoma at other anatomic sites, but patients present at an older median age. The clinical course is aggressive with a high frequency of disseminated disease at diagnosis; however, a subset of patients responds well to aggressive chemotherapy. PMID- 27257043 TI - A qualitative systematic review of service user and service provider perspectives on the acceptability, relative benefits, and potential harms of art therapy for people with non-psychotic mental health disorders. AB - PURPOSE: This systematic review aimed to synthesize qualitative evidence relating to user and service provider perspective on the acceptability and relative benefits and potential harms of art therapy for people with non-psychotic mental disorders. METHODS: A comprehensive literature search was conducted in 13 major bibliographic databases from May to July 2013. A qualitative evidence synthesis was conducted using thematic framework synthesis. RESULTS: The searches identified 10,270 citations from which 12 studies were included. Ten studies included data from 183 service users, and two studies included data from 16 service providers. The evidence demonstrated that art therapy was an acceptable treatment. The benefits associated with art therapy included the following: the development of relationships with the therapist and other group members; understanding the self/own illness/the future; gaining perspective; distraction; personal achievement; expression; relaxation; and empowerment. Small numbers of patients reported varying reasons for not wanting to take part, and some highlighted potentially negative effects of art therapy which included the evoking of feelings which could not be resolved. CONCLUSIONS: The findings suggest that for the majority of respondents art therapy was an acceptable intervention, although this was not the case for all respondents. Therefore, attention should be focussed on both identifying those who are most likely to benefit from art therapy and ensuring any potential harms are minimized. The findings provide evidence to commissioners and providers of mental health services about the value of future art therapy services. PRACTITIONER POINTS: Art therapy was reported to be an acceptable treatment for the majority of respondents. Art therapy may not be a preferred treatment option for a small number of patients, emphasizing the importance of considering patient preference in choice of treatment, and selection of the most suitable patients for art therapy. Consideration should be made of adjustments to make art therapy inclusive, particularly for those with physical illnesses. Ensuring the competence of the deliverer, providing patients with additional support, such as other therapies if required, and ensuring continuity of care should be key considerations in service provision. PMID- 27257044 TI - Contact-free monitoring of vessel graft stiffness - proof of concept as a tool for vascular tissue engineering. AB - Tissue-engineered vessel grafts have to mimic the biomechanical properties of native blood vessels. Manufacturing processes often condition grafts to adapt them to the target flow conditions. Graft stiffness is influenced by material properties and dimensions and determines graft compliance. This proof-of-concept study evaluated a contact-free method to monitor biomechanical properties without compromising sterility. Forced vibration response analysis was performed on human umbilical vein (HUV) segments mounted in a buffer-filled tubing system. A linear motor and a dynamic signal analyser were used to excite the fluid by white noise (0-200 Hz). Vein responses were read out by laser triangulation and analysed by fast Fourier transformation. Modal analysis was performed by monitoring multiple positions of the vessel surface. As an inverse model of graft stiffening during conditioning, HUV were digested proteolytically, and the course of natural frequencies (NFs) was monitored over 120 min. Human umbilical vein showed up to five modes with NFs in the range of 5-100 Hz. The first natural frequencies of HUV did not alter over time while incubated in buffer (p = 0.555), whereas both collagenase (-35%, p = 0.0061) and elastase (-45%, p < 0.001) treatments caused significant decreases of NF within 120 min. Decellularized HUV showed similar results, indicating that changes of the extracellular matrix were responsible for the observed shift in NF. Performing vibration response analysis on vessel grafts is feasible without compromising sterility or integrity of the samples. This technique allows direct measurement of stiffness as an important biomechanical property, obviating the need to monitor surrogate parameters. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27257045 TI - Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery. AB - Heme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We categorized patients as having the short allele (S; <27 GT repeats) or long allele (L; >=27 GT repeats), and defined AKI as an increase in serum creatinine >=0.3 mg/dl within 48 hours or >=50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene promoter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery associated AKI, and with HO-1 as a potential therapeutic target. PMID- 27257046 TI - Investigation of an Outbreak of Hepatitis A in a Coastal Area, Kerala, Southern India. AB - An outbreak investigation was initiated following an unusual occurrence of hepatitis A reported among people residing in the coastal belt of Vadi to Vedikunnu area, Kollam district, Kerala, southern India. The time frame of disease occurrence, pattern of its distribution, and the incubation period of hepatitis A infection indicated the probability of occurrence of the outbreak as a result of pipe line water contamination due to mixing of sewage from a canal. The results add evidence to the epidemiology of hepatitis A in the state and warrant the establishment of an efficient water quality surveillance system. PMID- 27257048 TI - Chronic hepatitis C and diabetes: More questions than answers with the new direct acting antiviral drugs? PMID- 27257047 TI - Aberrant functional brain connectome in people with antisocial personality disorder. AB - Antisocial personality disorder (ASPD) is characterised by a disregard for social obligations and callous unconcern for the feelings of others. Studies have demonstrated that ASPD is associated with abnormalities in brain regions and aberrant functional connectivity. In this paper, topological organisation was examined in resting-state fMRI data obtained from 32 ASPD patients and 32 non ASPD controls. The frequency-dependent functional networks were constructed using wavelet-based correlations over 90 brain regions. The topology of the functional networks of ASPD subjects was analysed via graph theoretical analysis. Furthermore, the abnormal functional connectivity was determined with a network based statistic (NBS) approach. Our results revealed that, compared with the controls, the ASPD patients exhibited altered topological configuration of the functional connectome in the frequency interval of 0.016-0.031 Hz, as indicated by the increased clustering coefficient and decreased betweenness centrality in the medial superior frontal gyrus, precentral gyrus, Rolandic operculum, superior parietal gyrus, angular gyrus, and middle temporal pole. In addition, the ASPD patients showed increased functional connectivity mainly located in the default mode network. The present study reveals an aberrant topological organisation of the functional brain network in individuals with ASPD. Our findings provide novel insight into the neuropathological mechanisms of ASPD. PMID- 27257050 TI - TACE vs DEB-TACE: Who wins? PMID- 27257049 TI - Ten-day empirical sequential or concomitant therapy is more effective than triple therapy for Helicobacter pylori eradication: A multicenter, prospective study. AB - BACKGROUND: The resistance of Helicobacter pylori to antibiotics has increased the need for new empirical, first-line treatments. However, the efficacy of sequential therapy (ST) and concomitant therapy (CT) compared with triple therapy (TT) has not been adequately evaluated. AIM: In this study, we evaluated the efficacy of these empirical three regimens. METHODS: The 517 patients enrolled in the study were prospectively randomized to receive 10 days of TT (n=171), ST (n=170), and CT (n=176) at 5 university-affiliated hospitals from May 2013 to March 2015. The post-treatment H. pylori status was determined using the (13)C urea breath test. RESULTS: The baseline characteristics were similar among the three groups. The intention-to-treat eradication rates were 62.6%, 70.6%, and 77.8% in the TT, ST, and CT groups, respectively (p<0.01). The corresponding per protocol eradication rates were 82.8%, 89.5%, and 94.4%, respectively (p<0.01). There were no significant differences in the compliance, side effects, and follow up loss rates. CONCLUSION: A higher eradication rate was achieved with empirical 10-day ST, and CT than with the TT regimen, with similar rates of compliance and treatment side effects. PMID- 27257051 TI - Methylenetetrahydrofolate dehydrogenase 2 overexpression is associated with tumor aggressiveness and poor prognosis in hepatocellular carcinoma. AB - BACKGROUND: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is the key enzyme in the transformation of folic acid metabolites. MTHFD2 overexpression plays a key role in the progression of human cancers, and depletion of MTHFD2 has shown potential antitumor activities in several types of cancer. However, the role of MTHFD2 in hepatocellular carcinoma (HCC) has not been investigated. AIMS: To investigate the expression of MTHFD2 in HCC patients, and its associated clinical implications and possible functions in HCC. METHODS: Reverse transcription polymerase chain reaction and immunohistochemical staining were used to detect MTHFD2 expression in liver tissues from HCC patients, then associations of MTHFD2 expression with demographic and clinicopathologic features were analysed. The effects of siRNA interference of MTHFD2 on cell proliferation, cell cycle, apoptosis, and migration were investigated in HCC cell lines. RESULTS: Significant overexpression of MTHFD2 was observed in HCC tissues, and overexpression of MTHFD2 was correlated with TNM stage, tumor microembolus, tumor metastasis, recurrence and the time of recurrence (P<0.05) in HCC patients. siRNA mediated silencing of MTHFD2 inhibited migration, invasion and epithelial mesenchymal transition progression in HCC cell lines, but no obvious effects on cell proliferation, apoptosis or cell cycle distribution were detected. CONCLUSIONS: MTHFD2 is overexpressed in HCC, and is associated with poor prognosis and cellular features connected to metastatic disease. PMID- 27257052 TI - Histamine is correlated with liver fibrosis in biliary atresia. AB - BACKGROUND AND AIMS: Biliary atresia (BA) is a severe neonatal cholestasis disease that is caused by obstruction of extra bile ducts. Liver fibrosis progresses dramatically in BA, and the underlying molecular mechanism is largely unknown. METHODS: Amino acids and biogenic amines were quantified by targeted metabolomic methods in livers of 52 infants with BA and 16 infants with neonatal hepatitis syndrome (NHS). Normal adjacent nontumor liver tissues from 5 hepatoblastoma infants were used as controls. Orthogonal partial least-squares discriminant analysis was used to identify the differences between BA, NHS, and control tissues. Histamine metabolism enzymes and receptors were analyzed by immunohistochemistry and Western blot. RESULTS: The orthogonal partial least squares discriminant analysis clearly separated BA from NHS and the controls using amino acid and biogenic amine profiles. Histamine was significantly increased in the livers of BA infants and was positively correlated with the severity of fibrosis. This finding was supported by the elevated l-histidine decarboxylase and reduced monoamine oxidase type B expressions in the BA infants with severe fibrosis. Furthermore, histamine receptor H1 was observed in the cholangiocytes of BA livers. CONCLUSIONS: Histamine was positively correlated with fibrosis and may be a potential target to prevent liver fibrosis in BA. PMID- 27257053 TI - The role of radical surgery in the management of CEAP C5/6 and lipodermatosclerosis. AB - Aim Analysis of the radical removing of the dermatosclerotic tissues and ulcer(s) with perforator veins dissection as well as local wound and standard compression treatment of CEAP C5/6 stage in a prospective comparative cohort study. Primary endpoint is to compare the results of the one-year follow-up regarding quality of life, vein clinical severity score, and ulcer healing process. Secondary endpoint is the precise presentation of the surgical technique. Tertiary endpoint is to demonstrate the photo-documented results of the postoperative wound treatment protocol. Method Clinical and statistical comparison of radical surgery versus solely wound care and compression in a cohort of 15 patients in each group (Groups 1, 2). In Group 1, radical removing of the dermatosclerotic pannicule and leg ulcer, perforator vein dissection, great saphenous vein, or small saphenous vein was performed. Quality of life , pain intensity, vein clinical severity score and patients' load capacity were compared. The tissue oxygen saturation changes were monitored via near infra-red spectroscopy. Results Both groups were statistically comparable. Wound healing in the operated group was 100% versus 60% in the second one, the difference was significant, p = 0.006. The quality of life: 45.33 versus 36.8, p < 0.001, intensity of leg restless and pain: 2.28 versus 5.3, p < 0.001, changes of vein clinical severity score: 5.27 versus 20.93, p < 0.001, changes of tO2sat: 19.00 versus 6.07 in the upper third of the leg p < 0.001, proved significantly better in group 1 compared to 2. Load capacity was significantly better in group 1 than 2 at the end of the study. The average wound healing time was 113 days in group 1. Conclusion The radical surgery provides significantly better results, considering quality of life, vein clinical severity score, load capacity than the conservative treatment in this study. PMID- 27257054 TI - Removing grain boundaries from three-dimensional colloidal crystals using active dopants. AB - Using computer simulations we explore how grain boundaries can be removed from three-dimensional colloidal crystals by doping with a small fraction of active colloids. We show that for sufficient self-propulsion, the system is driven into a crystal-fluid coexistence. In this phase separated regime, the active dopants become mobile and spontaneously gather at the grain boundaries. The resulting surface melting and recrystallization of domains result in the motion of the grain boundaries over time and lead to the formation of a large single crystal. However, when the self-propulsion is too low to cause a phase separation, we observe no significant enhancement of grain growth. PMID- 27257055 TI - Synergy and antagonism in regulation of recombinant human INO80 chromatin remodeling complex. AB - We have purified a minimal core human Ino80 complex from recombinant protein expressed in insect cells. The complex comprises one subunit each of an N terminally truncated Ino80, actin, Arp4, Arp5, Arp8, Ies2 and Ies6, together with a single heterohexamer of the Tip49a and Tip49b proteins. This core complex has nucleosome sliding activity that is similar to that of endogenous human and yeast Ino80 complexes and is also inhibited by inositol hexaphosphate (IP6). We show that IP6 is a non-competitive inhibitor that acts by blocking the stimulatory effect of nucleosomes on the ATPase activity. The IP6 binding site is located within the C-terminal region of the Ino80 subunit. We have also prepared complexes lacking combinations of Ies2 and Arp5/Ies6 subunits that reveal regulation imposed by each of them individually and synergistically that couples ATP hydrolysis to nucleosome sliding. This coupling between Ies2 and Arp5/Ies6 can be overcome in a bypass mutation of the Arp5 subunit that is active in the absence of Ies2. These studies reveal several underlying mechanisms for regulation of ATPase activity involving a complex interplay between these protein subunits and IP6 that in turn controls nucleosome sliding. PMID- 27257056 TI - A novel role for poly(C) binding proteins in programmed ribosomal frameshifting. AB - Translational control through programmed ribosomal frameshifting (PRF) is exploited widely by viruses and increasingly documented in cellular genes. Frameshifting is induced by mRNA secondary structures that compromise ribosome fidelity during decoding of a heptanucleotide 'slippery' sequence. The nsp2 PRF signal of porcine reproductive and respiratory syndrome virus is distinctive in directing both -2 and -1 PRF and in its requirement for a trans-acting protein factor, the viral replicase subunit nsp1beta. Here we show that the the trans activation of frameshifting is carried out by a protein complex composed of nsp1beta and a cellular poly(C) binding protein (PCBP). From the results of in vitro translation and electrophoretic mobility shift assays, we demonstrate that a PCBP/nsp1beta complex binds to a C-rich sequence downstream of the slippery sequence and here mimics the activity of a structured mRNA stimulator of PRF. This is the first description of a role for a trans-acting cellular protein in PRF. The discovery broadens the repertoire of activities associated with poly(C) binding proteins and prototypes a new class of virus-host interactions. PMID- 27257057 TI - Entropy gives rise to topologically associating domains. AB - We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains. PMID- 27257058 TI - Asymmetric exponential amplification reaction on a toehold/biotin featured template: an ultrasensitive and specific strategy for isothermal microRNAs analysis. AB - The sensitive and specific analysis of microRNAs (miRNAs) without using a thermal cycler instrument is significant and would greatly facilitate biological research and disease diagnostics. Although exponential amplification reaction (EXPAR) is the most attractive strategy for the isothermal analysis of miRNAs, its intrinsic limitations of detection efficiency and inevitable non-specific amplification critically restrict its use in analytical sensitivity and specificity. Here, we present a novel asymmetric EXPAR based on a new biotin/toehold featured template. A biotin tag was used to reduce the melting temperature of the primer/template duplex at the 5' terminus of the template, and a toehold exchange structure acted as a filter to suppress the non-specific trigger of EXPAR. The asymmetric EXPAR exhibited great improvements in amplification efficiency and specificity as well as a dramatic extension of dynamic range. The limit of detection for the let-7a analysis was decreased to 6.02 copies (0.01 zmol), and the dynamic range was extended to 10 orders of magnitude. The strategy enabled the sensitive and accurate analysis of let-7a miRNA in human cancer tissues with clearly better precision than both standard EXPAR and RT-qPCR. Asymmetric EXPAR is expected to have an important impact on the development of simple and rapid molecular diagnostic applications for short oligonucleotides. PMID- 27257059 TI - Ribosome recycling defects modify the balance between the synthesis and assembly of specific subunits of the oxidative phosphorylation complexes in yeast mitochondria. AB - Mitochondria have their own translation machinery that produces key subunits of the OXPHOS complexes. This machinery relies on the coordinated action of nuclear encoded factors of bacterial origin that are well conserved between humans and yeast. In humans, mutations in these factors can cause diseases; in yeast, mutations abolishing mitochondrial translation destabilize the mitochondrial DNA. We show that when the mitochondrial genome contains no introns, the loss of the yeast factors Mif3 and Rrf1 involved in ribosome recycling neither blocks translation nor destabilizes mitochondrial DNA. Rather, the absence of these factors increases the synthesis of the mitochondrially-encoded subunits Cox1, Cytb and Atp9, while strongly impairing the assembly of OXPHOS complexes IV and V. We further show that in the absence of Rrf1, the COX1 specific translation activator Mss51 accumulates in low molecular weight forms, thought to be the source of the translationally-active form, explaining the increased synthesis of Cox1. We propose that Rrf1 takes part in the coordination between translation and OXPHOS assembly in yeast mitochondria. These interactions between general and specific translation factors might reveal an evolutionary adaptation of the bacterial translation machinery to the set of integral membrane proteins that are translated within mitochondria. PMID- 27257060 TI - The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects. AB - Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. PMID- 27257061 TI - Increased cytoplasmic TARDBP mRNA in affected spinal motor neurons in ALS caused by abnormal autoregulation of TDP-43. AB - Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder. In motor neurons of ALS, TAR DNA binding protein-43 (TDP-43), a nuclear protein encoded by TARDBP, is absent from the nucleus and forms cytoplasmic inclusions. TDP-43 auto regulates the amount by regulating the TARDBP mRNA, which has three polyadenylation signals (PASs) and three additional alternative introns within the last exon. However, it is still unclear how the autoregulatory mechanism works and how the status of autoregulation in ALS motor neurons without nuclear TDP-43 is. Here we show that TDP-43 inhibits the selection of the most proximal PAS and induces splicing of multiple alternative introns in TARDBP mRNA to decrease the amount of cytoplasmic TARDBP mRNA by nonsense-mediated mRNA decay. When TDP-43 is depleted, the TARDBP mRNA uses the most proximal PAS and is increased in the cytoplasm. Finally, we have demonstrated that in ALS motor neurons-especially neurons with mislocalized TDP-43-the amount of TARDBP mRNA is increased in the cytoplasm. Our observations indicate that nuclear TDP-43 contributes to the autoregulation and suggests that the absence of nuclear TDP-43 induces an abnormal autoregulation and increases the amount of TARDBP mRNA. The vicious cycle might accelerate the disease progression of ALS. PMID- 27257062 TI - FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. AB - Forkhead box A1 (FOXA1) is an FKHD family protein that plays pioneering roles in lineage-specific enhancer activation and gene transcription. Through genome-wide location analyses, here we show that FOXA1 expression and occupancy are, in turn, required for the maintenance of these epigenetic signatures, namely DNA hypomethylation and histone 3 lysine 4 methylation. Mechanistically, this involves TET1, a 5-methylcytosine dioxygenase. We found that FOXA1 induces TET1 expression via direct binding to its cis-regulatory elements. Further, FOXA1 physically interacts with the TET1 protein through its CXXC domain. TET1 thus co occupies FOXA1-dependent enhancers and mediates local DNA demethylation and concomitant histone 3 lysine 4 methylation, further potentiating FOXA1 recruitment. Consequently, FOXA1 binding events are markedly reduced following TET1 depletion. Together, our results suggest that FOXA1 is not only able to recognize but also remodel the epigenetic signatures at lineage-specific enhancers, which is mediated, at least in part, by a feed-forward regulatory loop between FOXA1 and TET1. PMID- 27257063 TI - RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals. AB - DNA Topoisomerases are essential to resolve topological problems during DNA metabolism in all species. However, the prevalence and function of RNA topoisomerases remain uncertain. Here, we show that RNA topoisomerase activity is prevalent in Type IA topoisomerases from bacteria, archaea, and eukarya. Moreover, this activity always requires the conserved Type IA core domains and the same catalytic residue used in DNA topoisomerase reaction; however, it does not absolutely require the non-conserved carboxyl-terminal domain (CTD), which is necessary for relaxation reactions of supercoiled DNA. The RNA topoisomerase activity of human Top3beta differs from that of Escherichia coli topoisomerase I in that the former but not the latter requires the CTD, indicating that topoisomerases have developed distinct mechanisms during evolution to catalyze RNA topoisomerase reactions. Notably, Top3beta proteins from several animals associate with polyribosomes, which are units of mRNA translation, whereas the Top3 homologs from E. coli and yeast lack the association. The Top3beta polyribosome association requires TDRD3, which directly interacts with Top3beta and is present in animals but not bacteria or yeast. We propose that RNA topoisomerases arose in the early RNA world, and that they are retained through all domains of DNA-based life, where they mediate mRNA translation as part of polyribosomes in animals. PMID- 27257064 TI - Parallel analysis of ribonucleotide-dependent deletions produced by yeast Top1 in vitro and in vivo. AB - Ribonucleotides are the most abundant non-canonical component of yeast genomic DNA and their persistence is associated with a distinctive mutation signature characterized by deletion of a single repeat unit from a short tandem repeat. These deletion events are dependent on DNA topoisomerase I (Top1) and are initiated by Top1 incision at the relevant ribonucleotide 3'-phosphodiester. A requirement for the re-ligation activity of Top1 led us to propose a sequential cleavage model for Top1-dependent mutagenesis at ribonucleotides. Here, we test key features of this model via parallel in vitro and in vivo analyses. We find that the distance between two Top1 cleavage sites determines the deletion size and that this distance is inversely related to the deletion frequency. Following the creation of a gap by two Top1 cleavage events, the tandem repeat provides complementarity that promotes realignment to a nick and subsequent Top1-mediated ligation. Complementarity downstream of the gap promotes deletion formation more effectively than does complementarity upstream of the gap, consistent with constraints to realignment of the strand to which Top1 is covalently bound. Our data fortify sequential Top1 cleavage as the mechanism for ribonucleotide dependent deletions and provide new insight into the component steps of this process. PMID- 27257065 TI - The extended loops of ribosomal proteins uL4 and uL22 of Escherichia coli contribute to ribosome assembly and protein translation. AB - Nearly half of ribosomal proteins are composed of a domain on the ribosome surface and a loop or extension that penetrates into the organelle's RNA core. Our previous work showed that ribosomes lacking the loops of ribosomal proteins uL4 or uL22 are still capable of entering polysomes. However, in those experiments we could not address the formation of mutant ribosomes, because we used strains that also expressed wild-type uL4 and uL22. Here, we have focused on ribosome assembly and function in strains in which loop deletion mutant genes are the ONLY: sources of uL4 or uL22 protein. The uL4 and uL22 loop deletions have different effects, but both mutations result in accumulation of immature particles that do not accumulate in detectable amounts in wild-type strains. Thus, our results suggest that deleting the loops creates kinetic barriers in the normal assembly pathway, possibly resulting in assembly via alternate pathway(s). Furthermore, deletion of the uL4 loop results in cold-sensitive ribosome assembly and function. Finally, ribosomes carrying either of the loop-deleted proteins responded normally to the secM translation pausing peptide, but the uL4 mutant responded very inefficiently to the cmlA(crb) pause peptide. PMID- 27257066 TI - Quantitative modeling of gene expression using DNA shape features of binding sites. AB - Prediction of gene expression levels driven by regulatory sequences is pivotal in genomic biology. A major focus in transcriptional regulation is sequence-to expression modeling, which interprets the enhancer sequence based on transcription factor concentrations and DNA binding specificities and predicts precise gene expression levels in varying cellular contexts. Such models largely rely on the position weight matrix (PWM) model for DNA binding, and the effect of alternative models based on DNA shape remains unexplored. Here, we propose a statistical thermodynamics model of gene expression using DNA shape features of binding sites. We used rigorous methods to evaluate the fits of expression readouts of 37 enhancers regulating spatial gene expression patterns in Drosophila embryo, and show that DNA shape-based models perform arguably better than PWM-based models. We also observed DNA shape captures information complimentary to the PWM, in a way that is useful for expression modeling. Furthermore, we tested if combining shape and PWM-based features provides better predictions than using either binding model alone. Our work demonstrates that the increasingly popular DNA-binding models based on local DNA shape can be useful in sequence-to-expression modeling. It also provides a framework for future studies to predict gene expression better than with PWM models alone. PMID- 27257067 TI - The catalytic efficiency of yeast ribonuclease III depends on substrate specific product release rate. AB - Members of the ribonuclease III (RNase III) family regulate gene expression by triggering the degradation of double stranded RNA (dsRNA). Hundreds of RNase III cleavage targets have been identified and their impact on RNA maturation and stability is now established. However, the mechanism defining substrates' reactivity remains unclear. In this study, we developed a real-time FRET assay for the detection of dsRNA degradation by yeast RNase III (Rnt1p) and characterized the kinetic bottlenecks controlling the reactivity of different substrates. Surprisingly, the results indicate that Rnt1p cleavage reaction is not only limited by the rate of catalysis but can also depend on base-pairing of product termini. Cleavage products terminating with paired nucleotides, like the degradation signals found in coding mRNA sequence, were less reactive and more prone to inhibition than products having unpaired nucleotides found in non-coding RNA substrates. Mutational analysis of U5 snRNA and Mig2 mRNA confirms the pairing of the cleavage site as a major determinant for the difference between cleavage rates of coding and non-coding RNA. Together the data indicate that the base-pairing of Rnt1p substrates encodes reactivity determinants that permit both constitutive processing of non-coding RNA while limiting the rate of mRNA degradation. PMID- 27257068 TI - The human PMR1 endonuclease stimulates cell motility by down regulating miR-200 family microRNAs. AB - The motility of MCF-7 cells increases following expression of a human PMR1 transgene and the current study sought to identify the molecular basis for this phenotypic change. Ensemble and single cell analyses show increased motility is dependent on the endonuclease activity of hPMR1, and cells expressing active but not inactive hPMR1 invade extracellular matrix. Nanostring profiling identified 14 microRNAs that are downregulated by hPMR1, including all five members of the miR-200 family and others that also regulate invasive growth. miR-200 levels increase following hPMR1 knockdown, and changes in miR-200 family microRNAs were matched by corresponding changes in miR-200 targets and reporter expression. PMR1 preferentially cleaves between UG dinucleotides within a consensus YUGR element when present in the unpaired loop of a stem-loop structure. This motif is present in the apical loop of precursors to most of the downregulated microRNAs, and hPMR1 targeting of pre-miRs was confirmed by their loss following induced expression and increase following hPMR1 knockdown. Introduction of miR-200c into hPMR1-expressing cells reduced motility and miR-200 target gene expression, confirming hPMR1 acts upstream of Dicer processing. These findings identify a new role for hPMR1 in the post-transcriptional regulation of microRNAs in breast cancer cells. PMID- 27257069 TI - MutS regulates access of the error-prone DNA polymerase Pol IV to replication sites: a novel mechanism for maintaining replication fidelity. AB - Translesion DNA polymerases (Pol) function in the bypass of template lesions to relieve stalled replication forks but also display potentially deleterious mutagenic phenotypes that contribute to antibiotic resistance in bacteria and lead to human disease. Effective activity of these enzymes requires association with ring-shaped processivity factors, which dictate their access to sites of DNA synthesis. Here, we show for the first time that the mismatch repair protein MutS plays a role in regulating access of the conserved Y-family Pol IV to replication sites. Our biochemical data reveals that MutS inhibits the interaction of Pol IV with the beta clamp processivity factor by competing for binding to the ring. Moreover, the MutS-beta clamp association is critical for controlling Pol IV mutagenic replication under normal growth conditions. Thus, our findings reveal important insights into a non-canonical function of MutS in the regulation of a replication activity. PMID- 27257070 TI - ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells. AB - ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required. PMID- 27257071 TI - Goldmine integrates information placing genomic ranges into meaningful biological contexts. AB - Bioinformatic analysis often produces large sets of genomic ranges that can be difficult to interpret in the absence of genomic context. Goldmine annotates genomic ranges from any source with gene model and feature contexts to facilitate global descriptions and candidate loci discovery. We demonstrate the value of genomic context by using Goldmine to elucidate context dynamics in transcription factor binding and to reveal differentially methylated regions (DMRs) with context-specific functional correlations. The open source R package and documentation for Goldmine are available at http://jeffbhasin.github.io/goldmine. PMID- 27257072 TI - The structure and duplex context of DNA interstrand crosslinks affects the activity of DNA polymerase eta. AB - Several important anti-tumor agents form DNA interstrand crosslinks (ICLs), but their clinical efficiency is counteracted by multiple complex DNA repair pathways. All of these pathways require unhooking of the ICL from one strand of a DNA duplex by nucleases, followed by bypass of the unhooked ICL by translesion synthesis (TLS) polymerases. The structures of the unhooked ICLs remain unknown, yet the position of incisions and processing of the unhooked ICLs significantly influence the efficiency and fidelity of bypass by TLS polymerases. We have synthesized a panel of model unhooked nitrogen mustard ICLs to systematically investigate how the state of an unhooked ICL affects pol eta activity. We find that duplex distortion induced by a crosslink plays a crucial role in translesion synthesis, and length of the duplex surrounding an unhooked ICL critically affects polymerase efficiency. We report the synthesis of a putative ICL repair intermediate that mimics the complete processing of an unhooked ICL to a single crosslinked nucleotide, and find that it provides only a minimal obstacle for DNA polymerases. Our results raise the possibility that, depending on the structure and extent of processing of an ICL, its bypass may not absolutely require TLS polymerases. PMID- 27257073 TI - Heat shock represses rRNA synthesis by inactivation of TIF-IA and lncRNA dependent changes in nucleosome positioning. AB - Attenuation of ribosome biogenesis in suboptimal growth environments is crucial for cellular homeostasis and genetic integrity. Here, we show that shutdown of rRNA synthesis in response to elevated temperature is brought about by mechanisms that target both the RNA polymerase I (Pol I) transcription machinery and the epigenetic signature of the rDNA promoter. Upon heat shock, the basal transcription factor TIF-IA is inactivated by inhibition of CK2-dependent phosphorylations at Ser170/172. Attenuation of pre-rRNA synthesis in response to heat stress is accompanied by upregulation of PAPAS, a long non-coding RNA (lncRNA) that is transcribed in antisense orientation to pre-rRNA. PAPAS interacts with CHD4, the adenosine triphosphatase subunit of NuRD, leading to deacetylation of histones and movement of the promoter-bound nucleosome into a position that is refractory to transcription initiation. The results exemplify how stress-induced inactivation of TIF-IA and lncRNA-dependent changes of chromatin structure ensure repression of rRNA synthesis in response to thermo stress. PMID- 27257074 TI - Cas9-assisted recombineering in C. elegans: genome editing using in vivo assembly of linear DNAs. AB - Recombineering, the use of endogenous homologous recombination systems to recombine DNA in vivo, is a commonly used technique for genome editing in microbes. Recombineering has not yet been developed for animals, where non homology-based mechanisms have been thought to dominate DNA repair. Here, we demonstrate, using Caenorhabditis elegans, that linear DNAs with short homologies (~35 bases) engage in a highly efficient gene conversion mechanism. Linear DNA repair templates with homology to only one side of a double-strand break (DSB) initiate repair efficiently, and short overlaps between templates support template switching. We demonstrate the use of single-stranded, bridging oligonucleotides (ssODNs) to target PCR fragments for repair of DSBs induced by CRISPR/Cas9 on chromosomes. Based on these findings, we develop recombineering strategies for precise genome editing that expand the utility of ssODNs and eliminate in vitro cloning steps for template construction. We apply these methods to the generation of GFP knock-in alleles and gene replacements without co-integrated markers. We conclude that, like microbes, metazoans possess robust homology-dependent repair mechanisms that can be harnessed for recombineering and genome editing. PMID- 27257075 TI - A defect in homologous recombination leads to increased translesion synthesis in E. coli. AB - DNA damage tolerance pathways allow cells to duplicate their genomes despite the presence of replication blocking lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS) and homology directed gap repair (HDGR). TLS pathways involve specialized DNA polymerases that are able to synthesize past DNA lesions with an intrinsic risk of causing point mutations. In contrast, HDGR pathways are essentially error-free as they rely on the recovery of missing information from the sister chromatid by RecA-mediated homologous recombination. We have investigated the genetic control of pathway choice between TLS and HDGR in vivo in Escherichia coli In a strain with wild type RecA activity, the extent of TLS across replication blocking lesions is generally low while HDGR is used extensively. Interestingly, recA alleles that are partially impaired in D-loop formation confer a decrease in HDGR and a concomitant increase in TLS. Thus, partial defect of RecA's capacity to invade the homologous sister chromatid increases the lifetime of the ssDNA.RecA filament, i.e. the 'SOS signal'. This increase favors TLS by increasing both the TLS polymerase concentration and the lifetime of the TLS substrate, before it becomes sequestered by homologous recombination. In conclusion, the pathway choice between error-prone TLS and error-free HDGR is controlled by the efficiency of homologous recombination. PMID- 27257076 TI - Chromosome thripsis by DNA double strand break clusters causes enhanced cell lethality, chromosomal translocations and 53BP1-recruitment. AB - Chromosome translocations are hallmark of cancer and of radiation-induced cell killing, reflecting joining of incongruent DNA-ends that alter the genome. Translocation-formation requires DNA end-joining mechanisms and incompletely characterized, permissive chromatin conditions. We show that chromatin destabilization by clusters of DNA double-strand-breaks (DSBs) generated by the I SceI meganuclease at multiple, appropriately engineered genomic sites, compromises c-NHEJ and markedly increases cell killing and translocation formation compared to single-DSBs. Translocation-formation from DSB-clusters utilizes Parp1 activity, implicating alt-EJ in their formation. Immunofluorescence experiments show that single-DSBs and DSB-clusters uniformly provoke the formation of single gamma-H2AX foci, suggesting similar activation of early DNA damage response (DDR). Live-cell imaging also shows similar single focus recruitment of the early-response protein MDC1, to single-DSBs and DSB clusters. Notably, the late DDR protein, 53BP1 shows in live-cell imaging strikingly stronger recruitment to DSB-clusters as compared to single-DSBs. This is the first report that chromatin thripsis, in the form of engineered DSB clusters, compromises first-line DSB-repair pathways, allowing alt-EJ to function as rescuing-backup. DSB-cluster-formation is indirectly linked to the increased biological effectiveness of high ionization-density radiations, such as the alpha particles emitted by radon gas or the heavy-ions utilized in cancer therapy. Our observations provide the first direct mechanistic explanation for this long-known effect. PMID- 27257077 TI - Detection and visualization of differential splicing in RNA-Seq data with JunctionSeq. AB - Although RNA-Seq data provide unprecedented isoform-level expression information, detection of alternative isoform regulation (AIR) remains difficult, particularly when working with an incomplete transcript annotation. We introduce JunctionSeq, a new method that builds on the statistical techniques used by the well established DEXSeq package to detect differential usage of both exonic regions and splice junctions. In particular, JunctionSeq is capable of detecting differential usage of novel splice junctions without the need for an additional isoform assembly step, greatly improving performance when the available transcript annotation is flawed or incomplete. JunctionSeq also provides a powerful and streamlined visualization toolset that allows bioinformaticians to quickly and intuitively interpret their results. We tested our method on publicly available data from several experiments performed on the rat pineal gland and Toxoplasma gondii, successfully detecting known and previously validated AIR genes in 19 out of 19 gene-level hypothesis tests. Due to its ability to query novel splice sites, JunctionSeq is still able to detect these differences even when all alternative isoforms for these genes were not included in the transcript annotation. JunctionSeq thus provides a powerful method for detecting alternative isoform regulation even with low-quality annotations. An implementation of JunctionSeq is available as an R/Bioconductor package. PMID- 27257079 TI - Preparation of Magnetic Hollow Molecularly Imprinted Polymers for Detection of Triazines in Food Samples. AB - Novel magnetic hollow molecularly imprinted polymers (M-H-MIPs) were proposed for highly selective recognition and fast enrichment of triazines in food samples. M H-MIPs were prepared on the basis of multi-step swelling polymerization, followed by in situ growth of magnetic Fe3O4 nanoparticles on the surface of hollow molecularly imprinted polymers (H-MIPs). Transmission electron microscopy and scanning electron microscopy confirmed the successful immobilization of Fe3O4 nanoparticles on the surface of H-MIPs. M-H-MIPs could be separated simply using an external magnet. The binding adsorption results indicated that M-H-MIPs displayed high binding capacity and fast mass transfer property and class selective property for triazines. Langmuir isotherm and pseudo-second-order kinetic models fitted the best adsorption models for M-H-MIPs. M-H-MIPs were used to analyze atrazine, simazine, propazine, and terbuthylazine in corn, wheat, and soybean samples. Satisfactory recoveries were in the range of 80.62-101.69%, and relative standard deviation was lower than 5.2%. Limits of detection from 0.16 to 0.39 MUg L(-1) were obtained. When the method was applied to test positive samples that were contaminated with triazines, the results agree well with those obtained from an accredited method. Thus, the M-H-MIP-based dispersive solid phase extraction method proved to be a convenient and practical platform for detection of triazines in food samples. PMID- 27257078 TI - Profiling of 2'-O-Me in human rRNA reveals a subset of fractionally modified positions and provides evidence for ribosome heterogeneity. AB - Ribose methylation is one of the two most abundant modifications in human ribosomal RNA and is believed to be important for ribosome biogenesis, mRNA selectivity and translational fidelity. We have applied RiboMeth-seq to rRNA from HeLa cells for ribosome-wide, quantitative mapping of 2'-O-Me sites and obtained a comprehensive set of 106 sites, including two novel sites, and with plausible box C/D guide RNAs assigned to all but three sites. We find approximately two thirds of the sites to be fully methylated and the remainder to be fractionally modified in support of ribosome heterogeneity at the level of RNA modifications. A comparison to HCT116 cells reveals similar 2'-O-Me profiles with distinct differences at several sites. This study constitutes the first comprehensive mapping of 2'-O-Me sites in human rRNA using a high throughput sequencing approach. It establishes the existence of a core of constitutively methylated positions and a subset of variable, potentially regulatory positions, and paves the way for experimental analyses of the role of variations in rRNA methylation under different physiological or pathological settings. PMID- 27257080 TI - A Policy Analysis of Smoke-Free Legislation in Kentucky. AB - This article presents a policy analysis of proposed smoke-free legislation in Kentucky during the 2015 General Assembly. Kingdon's three streams model of agenda setting is used to analyze the failure to pass HB145. Secondhand smoke exposure and related deaths are a significant public health problem in Kentucky, a state with one of the highest smoking rates in the U.S. HB145, a comprehensive smoke-free bill, was designed to protect workers and the general public from secondhand smoke and e-cigarette aerosol in enclosed workplaces and public places, with few exemptions. The bill faced intense criticism from opponents who were concerned about violation of personal and business rights and the belief that the decision should be addressed on a local level. HB145 passed the House with amendments but failed to receive a hearing in the Senate. Failure of the smoke-free legislation was due to partisanship, fragmentation of advocacy groups, lack of political bargaining, and conflict of values. As in past years, the policy window did not open for state smoke-free legislation in 2015. PMID- 27257081 TI - A Structured Peer-Mentoring Method for Physical Activity Behavior Change Among Adolescents. AB - Despite national guidelines for regular physical activity, most adolescents are not physically active. Schools serve an estimated 60 million youth and provide an educational environment to meet the current physical activity guidelines. The obesity epidemic and chronic disease comorbidities associated with physical inactivity are not likely to be reversed without a strong contribution from local schools. This article describes how a structured peer-mentoring method provides a feasible, flexible, and tailored means to meet the current guidelines for best practice in a school setting. Structured peer mentoring using trained high school mentors to support behavior change in younger peers is an innovative method to meeting the School Health Guidelines to Promote Healthy Eating and Physical Activity Through structured peer mentoring, adolescents are provided consistent social support in a caring and personalized manner. This support builds skills and competencies enhancing self-efficacy to sustain a lifetime of physical activity behavior. PMID- 27257082 TI - In Vitro Fertilization Outcomes After Placement of Essure Microinserts in Patients With Hydrosalpinges Who Previously Failed In Vitro Fertilization Treatment: A Multicenter Study. AB - STUDY OBJECTIVE: To investigate whether hysteroscopic proximal tubal occlusion with Essure microinserts (Conceptus Inc.; Bayer, AG, North Rhine-Westphalia, Germany) can improve pregnancy rates in patients with hydrosalpinges who had failed in vitro fertilization (IVF) treatment. DESIGN: A prospective cohort study. SETTING: University-affiliated tertiary centers. PATIENTS: Twenty-four consecutive women with hydrosalpinges who had failed IVF treatment were included. INTERVENTIONS: Hysteroscopic placement of Essure microinserts for hydrosalpinx blockage followed by IVF treatment. MEASUREMENTS AND MAIN RESULTS: Ongoing pregnancy and live birth rates were recorded. Of the 24 patients undergoing a total of 42 IVF cycles after Essure insertion, 18 (75% of patients and 42.8% of IVF cycle attempts) conceived and 16 delivered live births (66.6% of patients and 38.1% of IVF cycle attempts). CONCLUSION: Hysteroscopic proximal occlusion of hydrosalpinges with Essure microinserts is a valuable alternative to laparoscopic salpingectomy, resulting in reasonable pregnancy rates. PMID- 27257083 TI - Confirmation Testing of Essure Microinserts in Unintended Pregnancies Using a 10 Year Retrospective Database. AB - STUDY OBJECTIVES: To examine the imaging modality used in cases of Essure failures and determine the cause of the unintended pregnancies (noncompliance to follow-up recommendations, misinterpretation of the imaging test, or device failure). DESIGN: Retrospective, single-center interventional cohort (Canadian Task Force classification II-2). SETTING: Tertiary level hospital. PATIENTS: Women who have had Essure placement and subsequent pregnancy. INTERVENTIONS: Coding data from the Regina General Hospital was examined for any pregnancy occurring after an Essure procedure. The hospital charts were then reviewed for data collection. A separate imaging database established over the same time frame was then reviewed to determine the imaging modality used in each case (transvaginal ultrasound [TVU], hysterosalpingogram [HSG], or none). Results of the imaging study were reviewed and the cause of the failure determined. MEASUREMENTS AND MAIN RESULTS: Twenty-four pregnancies in 25 women were identified after Essure procedures from January 1, 2003 to March 31, 2013. There were 4 in vitro fertilization pregnancies and 4 pregnancies where the woman had been instructed not to rely on the devices because of incomplete placement noted at time of the procedure. Therefore, 17 unintended pregnancies occurred of a total 2080 procedures performed. Examination of the imaging studies revealed that 11 were due to patient noncompliance (either early cessation of backup contraception or failure to go for confirmatory imaging), 5 due to misinterpretation of the imaging tests (3 HSG, 2 TVU), and 1 device failure. This reveals a cumulative failure rate of 6 of 2080 or .29% over 10 years with only .04% (1/2080) being device related. CONCLUSION: Essure sterilization is an effective means of permanent contraception with a device failure rate of only .04%. Most unintended pregnancies after the Essure procedure result from a failure to comply with follow-up recommendations, and strategies to improve compliance should be emphasized. PMID- 27257084 TI - Gigapixel surface imaging of radical prostatectomy specimens for comprehensive detection of cancer-positive surgical margins using structured illumination microscopy. AB - Achieving cancer-free surgical margins in oncologic surgery is critical to reduce the need for additional adjuvant treatments and minimize tumor recurrence; however, there is a delicate balance between completeness of tumor removal and preservation of adjacent tissues critical for normal post-operative function. We sought to establish the feasibility of video-rate structured illumination microscopy (VR-SIM) of the intact removed tumor surface as a practical and non destructive alternative to intra-operative frozen section pathology, using prostate cancer as an initial target. We present the first images of the intact human prostate surface obtained with pathologically-relevant contrast and subcellular detail, obtained in 24 radical prostatectomy specimens immediately after excision. We demonstrate that it is feasible to routinely image the full prostate circumference, generating gigapixel panorama images of the surface that are readily interpreted by pathologists. VR-SIM confirmed detection of positive surgical margins in 3 out of 4 prostates with pathology-confirmed adenocarcinoma at the circumferential surgical margin, and furthermore detected extensive residual cancer at the circumferential margin in a case post-operatively classified by histopathology as having negative surgical margins. Our results suggest that the increased surface coverage of VR-SIM could also provide added value for detection and characterization of positive surgical margins over traditional histopathology. PMID- 27257086 TI - Incorporating albumin-bilirubin grade into the cancer of the liver Italian program system for hepatocellular carcinoma. AB - BACKGROUND AND AIMS: The albumin-bilirubin (ALBI) grade is a recently emerging alternative of the Child-Pugh (CP) grade. The Cancer of the Liver Italian Program (CLIP) was demonstrated to be a useful prognostic model for hepatocellular carcinoma (HCC) in large prospective cohorts. We aimed to investigate the feasibility of substituting the CP grade by the ALBI grade in the CLIP system and compare the prognostic performance with other existing staging systems. METHODS: A large cohort of 1973 Chinese patients with HCC was recruited to evaluate the prognostic performance of CP-based CLIP (CP-CLIP) and ALBI-based CLIP (ALBI-CLIP) systems and nine other staging systems by homogeneity likelihood chi-square, c index, and corrected Akaike information criterion. RESULTS: The ALBI-CLIP system provided comparable prognostic performance than the CP-CLIP system, which was indicated by homogeneity likelihood chi-squares (ALBI-CLIP 1186.35 vs CP-CLIP 1145.54), c-indices (ALBI-CLIP 0.789 vs CP-CLIP 0.785) and AICs (ALBI-CLIP 15 493.47 vs CP-CLIP 15 534.28). Among 11 staging systems, ALBI-CLIP and CP-CLIP systems were associated with the highest homogeneity chi-squares and c-indices, and the lowest corrected Akaike information criterion. Patients in ALBI-CLIP score 0-4 had better median survival than those in corresponding CP-CLIP score. CONCLUSIONS: The ALBI grade performs as well as the CP grade when integrating into the CLIP system. ALBI-CLIP and CP-CLIP systems are the most accurate prognostic models among 11 existing staging systems. PMID- 27257087 TI - APPL1 gates long-term potentiation through its plekstrin homology domain. AB - Hippocampal synaptic plasticity involves both membrane trafficking events and intracellular signaling, but how these are coordinated is far from clear. The endosomal transport of glutamate receptors in and out of the postsynaptic membrane responds to multiple signaling cascades triggered by synaptic activity. In this work, we have identified adaptor protein containing a plekstrin homology domain, phosphotyrosine-binding domain and leucine zipper motif 1 (APPL1) as a crucial element linking trafficking and signaling during synaptic plasticity. We show that APPL1 knockdown specifically impairs PI3K-dependent forms of synaptic plasticity, such as long-term potentiation (LTP) and metabotropic-glutamate receptor-dependent long-term depression (mGluR-LTD). Indeed, we demonstrate that APPL1 is required for the activation of the phosphatidylinositol triphosphate (PIP3) pathway in response to LTP induction. This requirement can be bypassed by membrane localization of PI3K and is related to phosphoinositide binding. Interestingly, inhibitors of PDK1 (also known as PDPK1) and Akt have no effect on LTP expression. Therefore, we conclude that APPL1 gates PI3K activation at the plasma membrane upon LTP induction, which is then relayed by downstream PIP3 effectors that are different from PDK1 and Akt. PMID- 27257085 TI - The effector AWR5 from the plant pathogen Ralstonia solanacearum is an inhibitor of the TOR signalling pathway. AB - Bacterial pathogens possess complex type III effector (T3E) repertoires that are translocated inside the host cells to cause disease. However, only a minor proportion of these effectors have been assigned a function. Here, we show that the T3E AWR5 from the phytopathogen Ralstonia solanacearum is an inhibitor of TOR, a central regulator in eukaryotes that controls the switch between cell growth and stress responses in response to nutrient availability. Heterologous expression of AWR5 in yeast caused growth inhibition and autophagy induction coupled to massive transcriptomic changes, unmistakably reminiscent of TOR inhibition by rapamycin or nitrogen starvation. Detailed genetic analysis of these phenotypes in yeast, including suppression of AWR5-induced toxicity by mutation of CDC55 and TPD3, encoding regulatory subunits of the PP2A phosphatase, indicated that AWR5 might exert its function by directly or indirectly inhibiting the TOR pathway upstream PP2A. We present evidence in planta that this T3E caused a decrease in TOR-regulated plant nitrate reductase activity and also that normal levels of TOR and the Cdc55 homologues in plants are required for R. solanacearum virulence. Our results suggest that the TOR pathway is a bona fide T3E target and further prove that yeast is a useful platform for T3E function characterisation. PMID- 27257088 TI - Ttll9-/- mice sperm flagella show shortening of doublet 7, reduction of doublet 5 polyglutamylation and a stall in beating. AB - Nine outer doublet microtubules in axonemes of flagella and cilia are heterogeneous in structure and biochemical properties. In mammalian sperm flagella, one of the factors to generate the heterogeneity is tubulin polyglutamylation, although the importance of the heterogeneous modification is unclear. Here, we show that a tubulin polyglutamylase Ttll9 deficiency (Ttll9(-/ )) causes a unique set of phenotypes related to doublet heterogeneity. Ttll9(-/-) sperm axonemes had frequent loss of a doublet and reduced polyglutamylation. Intriguingly, the doublet loss selectively occurred at the distal region of doublet 7, and reduced polyglutamylation was observed preferentially on doublet 5. Ttll9(-/-) spermatozoa showed aberrant flagellar beating, characterized by frequent stalls after anti-hook bending. This abnormal motility could be attributed to the reduction of polyglutamylation on doublet 5, which probably occurred at a position involved in the switching of bending. These results indicate that mammalian Ttll9 plays essential roles in maintaining the normal structure and beating pattern of sperm flagella by establishing normal heterogeneous polyglutamylation patterns. PMID- 27257089 TI - Incident Angle- and Polarization-Insensitive Metamaterial Absorber using Circular Sectors. AB - In this paper, an incident angle- and polarization-insensitive metamaterial absorber is proposed for X-band applications. A unit cell of the proposed absorber has a square patch at the centre and four circular sectors are rotated around the square patch. The vertically and horizontally symmetric structure of the unit cell enables polarization-insensitivity. The circular sector of the unit cell enables an angle-insensitivity. The performances of the proposed absorber are demonstrated with a full-wave simulation and measurements. The angular sensitivity is studied at different inner angles of the circular sector. When the inner angle of the circular sector is 90 degrees , the simulated absorptivity is higher than 90%, and the frequency variation is less than 0.96% for incident angles up to 70 degrees . The measured absorptivity at 10.44 GHz is close to 100% for all the polarization angles under normal incidence. When the incident angles are varied from 0 degrees - 60 degrees , the measured absorptivity is maintained above 90% for both the transverse electric (TE) and the transverse magnetic (TM) modes. PMID- 27257090 TI - Evaluating Ultra-long-Chain Fatty Acids as Biomarkers of Colorectal Cancer Risk. AB - BACKGROUND: Cross-sectional studies reported a novel set of hydroxylated ultra long-chain fatty acids (ULCFA) that were present at significantly lower levels in colorectal cancer cases than controls. Follow-up studies suggested that these molecules were potential biomarkers of protective exposure for colorectal cancer. To test the hypothesis that ULCFAs reflect causal pathways, we measured their levels in prediagnostic serum from incident colorectal cancer cases and controls. METHODS: Serum from 95 colorectal cancer patients and 95 matched controls was obtained from the Italian arm of the European Prospective Investigation into Cancer and Nutrition cohort and analyzed by liquid chromatography-high-resolution mass spectrometry. Levels of 8 ULCFAs were compared between cases and controls with paired t tests and a linear model that used time to diagnosis (TTD) to determine whether case-control differences were influenced by disease progression. RESULTS: Although paired t tests detected significantly lower levels of four ULCFAs in colorectal cancer cases, confirming earlier reports, the case control differences diminished significantly with increasing TTD (7 days-14 years). CONCLUSION: Levels of several ULCFAs were lower in incident colorectal cancer cases than controls. However, because case-control differences decreased with increasing TTD, we conclude that these molecules were likely consumed by processes related to cancer progression rather than causal pathways. IMPACT: ULCFA levels are unlikely to represent exposures that protect individuals from colorectal cancer. Future research should focus on the diagnostic potential and origins of these molecules. Our use of TTD as a covariate in a linear model provides an efficient method for distinguishing causal and reactive biomarkers in biospecimens from prospective cohorts. Cancer Epidemiol Biomarkers Prev; 25(8); 1216-23. (c)2016 AACR. PMID- 27257091 TI - Long-term Particulate Matter Exposures during Adulthood and Risk of Breast Cancer Incidence in the Nurses' Health Study II Prospective Cohort. AB - BACKGROUND: There is increasing concern that environmental exposures, such as air pollution, may be related to increasing rates of breast cancer; however, results from cohort studies have been mixed. We examined the association between particulate matter (PM) and measures of distance to roadway with the risk of incident breast cancer in the prospective nationwide Nurses' Health Study II (NHSII) cohort. METHODS: Incident invasive breast cancer from 1993 to 2011 (N = 3,416) was assessed among 115,921 women in the NHSII cohort. Time-varying Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (95% CI) for increases in ambient exposures to PM10, PM2.5-10, and PM2.5 and residential roadway proximity categories. RESULTS: In multivariable adjusted models, there was little evidence of an increased risk of breast cancer (or any of the receptor-specific subtypes) overall or by menopausal status with PM exposure. There was, however, a suggestion of increased risks among women living <50 m of the largest road type (HR = 1.60; 95% CI, 0.80-3.21) or within <50 m of the two largest road types (1.14; 95% CI, 0.84-1.54) compared with women living farther (>=200 m) away. CONCLUSIONS: Among women in the NHSII, we found no statistically significant associations between particulate matter exposures and incidence of breast cancer overall, by menopausal status, or by hormone receptor subtype. There was, however, a suggestion that residential proximity to major roadways may be associated with increased risk. IMPACT: These results suggest no elevated breast cancer risk with increasing exposures to particulate matter air pollution, but that other traffic-related exposures may be important. Cancer Epidemiol Biomarkers Prev; 25(8); 1274-6. (c)2016 AACR. PMID- 27257092 TI - Treatment Preferences for Active Surveillance versus Active Treatment among Men with Low-Risk Prostate Cancer. AB - BACKGROUND: Due to the concerns about the overtreatment of low-risk prostate cancer, active surveillance (AS) is now a recommended alternative to the active treatments (AT) of surgery and radiotherapy. However, AS is not widely utilized, partially due to psychological and decision-making factors associated with treatment preferences. METHODS: In a longitudinal cohort study, we conducted pretreatment telephone interviews (N = 1,140, 69.3% participation) with newly diagnosed, low-risk prostate cancer patients (PSA <= 10, Gleason <= 6) from Kaiser Permanente Northern California. We assessed psychological and decision making variables, and treatment preference [AS, AT, and No Preference (NP)]. RESULTS: Men were 61.5 (SD, 7.3) years old, 24 days (median) after diagnosis, and 81.1% white. Treatment preferences were: 39.3% AS, 30.9% AT, and 29.7% NP. Multinomial logistic regression revealed that men preferring AS (vs. AT) were older (OR, 1.64; CI, 1.07-2.51), more educated (OR, 2.05; CI, 1.12-3.74), had greater prostate cancer knowledge (OR, 1.77; CI, 1.43-2.18) and greater awareness of having low-risk cancer (OR, 3.97; CI, 1.96-8.06), but also were less certain about their treatment preference (OR, 0.57; CI, 0.41-0.8), had greater prostate cancer anxiety (OR, 1.22; CI, 1.003-1.48), and preferred a shared treatment decision (OR, 2.34; CI, 1.37-3.99). Similarly, men preferring NP (vs. AT) were less certain about treatment preference, preferred a shared decision, and had greater knowledge. CONCLUSIONS: Although a substantial proportion of men preferred AS, this was associated with anxiety and uncertainty, suggesting that this may be a difficult choice. IMPACT: Increasing the appropriate use of AS for low-risk prostate cancer will require additional reassurance and information, and reaching men almost immediately after diagnosis while the decision-making is ongoing. Cancer Epidemiol Biomarkers Prev; 25(8); 1240-50. (c)2016 AACR. PMID- 27257093 TI - Lichen Sclerosus: Incidence and Risk of Vulvar Squamous Cell Carcinoma. AB - BACKGROUND: The association between lichen sclerosus and vulvar squamous cell carcinoma (VSCC) has long been recognized, but large epidemiologic studies are lacking. METHODS: Data of women diagnosed with vulvar pathology in the Netherlands were retrieved from the Dutch Pathology Registry. All vulvar pathology reports of this historical cohort were reviewed to construct a research database, including 3,038 women with lichen sclerosus diagnosed between 1991 and 2011. The incidence rate of lichen sclerosus and the cumulative incidence of VSCC among women with lichen sclerosus were estimated. RESULTS: Between 1991 and 2011, the incidence rate of lichen sclerosus increased from 7.4 to 14.6 per 100,000 woman-years. The median age at time of lichen sclerosus diagnosis was 59.8 years and the cumulative VSCC incidence was 6.7%. The 10-year VSCC incidence in women with lichen sclerosus was associated with concurrent vulvar intraepithelial neoplasia (VIN; 18.8% in women with VIN and 2.8% in women without VIN) and age at time of lichen sclerosus diagnosis (5.9% in women of >=70 years, 3% in women between 50 and 70 years, and 1.8% in women <50 years). The effects of presence of VIN and age remained significant in adjusted Cox regression analysis. CONCLUSION: This historical cohort showed a nearly 100% increase in incidence of lichen sclerosus between 1991 and 2011. Concurrent VIN and age >=70 years at time of lichen sclerosus diagnosis are important risk factors for vulvar cancer development. IMPACT: The incidence of lichen sclerosus is rising and special attention is needed in particular in women with concurrent VIN because of their high risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(8); 1224-30. (c)2016 AACR. PMID- 27257094 TI - Early Detection of Symptomatic Paroxysmal Cardiac Arrhythmias by Trans-Telephonic ECG Monitoring: Impact on Diagnosis and Treatment of Atrial Fibrillation. AB - INTRODUCTION: Diagnosis of infrequent cardiac arrhythmias (CA) is often unsuccessful using resting or Holter ECG. As early detection and treatment of CA, especially atrial fibrillation (AF), has implications on patients' treatment and outcome, we investigated, whether self-guided, trans-telephonic event-recorder monitoring (Tele-ECG) improves diagnosis and influences treatment options. METHODS: Between 2009 and 2014, 790 patients (54 +/- 18 years, 40% male; no history of CA: 582, known AF: 179, other CA: 29) presented with recurrent symptoms suggestive of CA and were screened by Tele-ECG (17.3 +/- 26.9 days). A total of 11,775 ECGs were transmitted via a 24-hour telephone hotline including documentation of the respective symptoms. RESULTS: In 73% of patients, CA was documented at the time of symptoms: sinus tachycardia 23%, premature ventricular beats 19%, AF 14%, supraventricular tachycardia 9%, sinus bradycardia 5%, sinus arrhythmia 2%, and AV block II 1%. The mean time until the first symptomatic episode occurred was 6.9 +/- 15.3 days (median 2.5 days). The first documented arrhythmia occurred on average after 7.7 +/- 14.1 days (median 3 days). In patients with AF (n = 110), 44% was newly diagnosed. According to the Tele-ECG diagnosis, AF ablation was performed in 27% of these patients, 7% electrical cardioversion, and in 30% antiarrhythmic therapy was initiated. In 65% of the patients with recurrence of known AF, (re-)ablation was performed or recommended and in 16% antiarrhythmic therapy was modified. CONCLUSIONS: Tele-ECG monitoring is effective in the diagnosis of suspected symptomatic CA. A diagnosis can usually be achieved within 1 week and has implications on patients' care. PMID- 27257095 TI - Granular gel support-enabled extrusion of three-dimensional alginate and cellular structures. AB - Freeform fabrication of soft structures has been of great interest in recent years. In particular, it is viewed as a critical step toward the grand vision of organ printing--the on-demand design and fabrication of three-dimensional (3D) human organ constructs for implantation and regenerative medicine. The objective of this study is to develop a novel granular gel support material-enabled, two step gelation-based 'printing-then-gelation' approach to fabricate 3D alginate structures using filament extrusion. Specifically, a granular Carbopol microgel bath holds the ungelled alginate structure being extruded, avoiding the instantaneous gelation of each printed layer as well as resultant surface tension induced nozzle clogging. Since Carbopol microgels react with multivalent cations, which are needed for alginate crosslinking, gelatin is introduced as a sacrificial material to make an alginate and gelatin bioink for extrusion, which gels thermally (step-one gelation) to initially stabilize the printed structure for removal from Carbopol. Then gelatin is melted and diffused away while alginate is ionically crosslinked in a 37 degrees C calcium chloride bath (step two gelation), resulting in an alginate structure. The proposed 'printing-then gelation' approach works for alginate structure fabrication, and it is also applicable for the printing of cellular constructs and other similar homogeneous soft structures using a two-step or even multi-step approach. The main conclusions are: (1) 0.8% (w/v) Carbopol bath with a neutral pH value may be most suitable for soft structure printing; (2) it is most effective to use a 0.9% (w/v) NaCl solution to facilitate the removal of residual Carbopol; and (3) alginate structures fabricated using the proposed approach demonstrate better mechanical properties than those fabricated using the conventional 'gelation while-printing' approach. PMID- 27257096 TI - The Enigmatic Universe of the Herbivore Gut. AB - The herbivore gut is a fascinating ecosystem exquisitely adapted to plant biomass degradation. Within this ecosystem, anaerobic fungi invade biomass and secrete hydrolytic enzymes. In a recent study, Solomon et al. characterized three anaerobic fungi by transcriptomics, proteomics, and functional analyses to identify novel components essential for plant biomass deconstruction. PMID- 27257097 TI - The Contagion of Interstate Violence: Reminders of Historical Interstate (but Not Intrastate) Violence Increase Support for Future Violence Against Unrelated Third Party States. AB - Five experiments investigated the war contagion phenomenon in the context of international relations, hypothesizing that reminders of past inter- (but not intra-) state war will increase support for future, unrelated interstate violence. After being reminded of the Korean War as an interstate rather than intrastate conflict, South Koreans showed stronger support for violent responses to new, unrelated interstate tensions (Study 1). Replicating this war contagion effect among Americans, we demonstrated that it was mediated by heightened perceived threat from, and negative images of, a fictitious country unrelated to the past war (Study 2), and moderated by national glorification (Study 3). Study 4, using another international conflict in the U.S. history, provided further conceptual replication. Finally, Study 5 included a baseline in addition to the inter- versus intrastate manipulation, yielding further support for the generalized effect of past interstate war reminders on preferences for aggressive approaches to new interstate tensions. PMID- 27257098 TI - Achondroplasia: Really rhizomelic? AB - Achondroplasia is the most common form of short limb dwarfism in humans. The shortening of the limb lengths in achondroplasia is widely described as "rhizomelic." While this appearance may be convincing clinically, the description is not necessarily true or helpful radiologically. The aims of this study, were therefore, to determine whether rhizomelic shortening is a true feature of achondroplasia at diagnosis in infancy. Humeral, radial, femoral, and tibial diaphyseal lengths were recorded by two independent observers from 22 skeletal surveys of infants with achondroplasia and compared with 150 normal age-matched control subjects. Upper and lower limb bone length ratios (radial/humeral and tibial/femoral lengths, respectively) in both groups were compared using an unpaired t-test. Mean upper limb length ratios were statistically higher within the achondroplasia group at 0.87 +/- 0.04 (n = 22, mean age 70 +/- 94 days) compared to normal controls at 0.79 +/- 0.02 (n = 150, mean age 113 days +/- 88 days; P < 0.0001). Lower limb length ratios were not significantly different between groups (0.84 +/- 0.04 vs. 0.83 +/- 0.02, P = 0.46). There was good inter observer agreement of limb length measurements, with an average measurement difference of 0.1 +/- 1.4 mm. In conclusion, infants with achondroplasia demonstrate statistically significant rhizomelic shortening within the upper limbs, but not lower limbs at diagnosis, compared to normal controls. The term "rhizomelic shortening" in relation to achondroplasia should be reserved when describing upper limb proportions. (c) 2016 Wiley Periodicals, Inc. PMID- 27257099 TI - Perceived Physical Appearance: Assessing Measurement Equivalence in Black, Latino, and White Adolescents. AB - Objective: This aim of this study was to examine whether the construct of physical appearance perception differed among the three largest racial/ethnic groups in the United States using an adolescent sample. Methods: Black (46%), Latino (31%), and White (23%) adolescents in Grade 10 from the Healthy Passages study ( N = 4,005) completed the Harter's Self-Perception Profile for Adolescents-Physical Appearance Scale (SPPA-PA) as a measure of physical appearance perception. Results: Overall, Black adolescents had a more positive self-perception of their physical appearance than Latino and White adolescents. However, further analysis using measurement invariance testing revealed that the construct of physical appearance perception, as measured by SPPA-PA, was not comparable across the three racial/ethnic groups in both males and females. Conclusions: These results suggest that observed differences may not reflect true differences in perceptions of physical appearance. Measures that are equivalent across racial/ethnic groups should be developed to ensure more precise measurement and understanding. PMID- 27257100 TI - Secondary stenting of glaucoma drainage implant: a novel technique for treatment of late hypotony. PMID- 27257101 TI - Rheological and mechanical properties and interfacial stress development of composite cements modified with thio-urethane oligomers. AB - OBJECTIVES: Thio-urethane oligomers have been shown to reduce stress and increase toughness in highly filled composite materials. This study evaluated the influence of thio-urethane backbone structure on rheological and mechanical properties of resin cements modified with a fixed concentration of the oligomers. METHODS: Thio-urethane oligomers (TU) were synthesized by combining thiols - pentaerythritol tetra-3-mercaptopropionate (PETMP) or trimethylol-tris-3 mercaptopropionate (TMP) - with isocyanates - 1,6-hexanediol-diissocyante (HDDI) (aliphatic) or 1,3-bis(1-isocyanato-1-methylethyl)benzene (BDI) (aromatic) or dicyclohexylmethane 4,4'-diisocyanate (HMDI) (cyclic), at 1:2 isocyanate:thiol, leaving pendant thiols. 20wt% TU were added to BisGMA-UDMA-TEGDMA (5:3:2). 60wt% silanated inorganic fillers were added. Near-IR was used to follow methacrylate conversion and rate of polymerization ( [Formula: see text] ). Mechanical properties were evaluated in three-point bending (ISO 4049) for flexural strength/modulus (FS/FM, and toughness), and notched specimens (ASTM Standard E399-90) for fracture toughness (KIC). PS was measured on the Bioman. Viscosity (V) and gel-points (defined as the crossover between storage and loss shear moduli (G'/G")) were obtained with rheometry. Glass transition temperature (Tg), cross-link density and homogeneity of the network were obtained with dynamic mechanical analysis. Film-thickness was evaluated according to ISO 4049. RESULTS: DC and mechanical properties increased and [Formula: see text] and PS decreased with the addition of TUs. Gelation (G'/G") was delayed and DC at G'/G" increased in TU groups. Tg and cross-link density dropped in TU groups, while oligomers let to more homogenous networks. An increase in V was observed, with no effect on film-thickness. Significant reductions in PS were achieved at the same time conversion and mechanical properties increased. SIGNIFICANCE: The addition of thio-urethane oligomers proved successful in improving several key properties of resin cements, without disrupting the procedures dentists use to polymerize the material. This approach has potential to be translated to commercial materials very readily. PMID- 27257102 TI - Potential confounders of bisphenol-a analysis in dental materials. AB - OBJECTIVES: In the published literature, a variety of analytical methods have been used to quantify and report bisphenol A (BPA) release from dental resins. The objective of this study was to compare results obtained for quantification of BPA in dental resin extracts using an LC/UV analytical method and an LC/MS/MS method. METHODS: A cured Bis-GMA-based resin representative of commercial dental products was extracted according to ISO 10993 guidelines for medical devices. d16BPA was included as an internal standard. Sample processing followed expert recommendations for minimizing BPA sample contamination. Extracts were separated using HPLC methods and analyzed for BPA using LC/UV and LC/MS/MS detection methods. RESULTS: The reported BPA concentrations were about 30-fold higher using LC/UV vs. LC/MS/MS. Full scan LC/MS/MS in both positive and negative modes showed that the apparent high BPA values seen with LC/UV were caused by co-elution of a previously unidentified chemical, thought to arise from one of the polymerization initiators. SIGNIFICANCE: These results emphasize the potential difficulties in obtaining accurate analyses of BPA in complex mixtures such as dental resins and their extracts. Both good separation methodology and a detection method with high specificity and sensitivity are important to avoid incorrect identification of extractables, and consequent incorrect quantitative assignments for species of interest. Reliable methods are essential for accurate estimation of patient exposure to BPA and development of meaningful health risk assessments. PMID- 27257103 TI - [Can positron emission tomography assessment of response to treatment help to individualize use of erlotinib in non-small cell lung cancer?] AB - Erlotinib can be prescribed in the treatment of locally advanced or metastatic non-small lung cancer cell (NSCLC) after failure of at least one prior chemotherapy regimen on the basis of the BR-21 study. Several publications have recently questioned these results. The metabolic imaging of solid tumours by positron emission tomography is a research field that could help customize the treatment of NSCLC and so complement the treatment approaches allowed by genetic analyses. This strategy is part of an innovative "early metabolic look" approach. The primary objective of this study is to determine if metabolic progression observed between the 7th and 14th day after initiation of treatment with erlotinib by 3'-Deoxy-3'-[18F]-Fluorothymidine PET in patients with EGFR naive NSCLC is predictive for morphological progression after 6 to 8 weeks of treatment. A health economic analysis will be conducted. This study is particularly innovative because it begins the exploration of the era of metabolic evaluation of therapeutic response in NSCLC. PMID- 27257105 TI - Mammalian metabolic rates in the hottest fish on earth. AB - The Magadi tilapia, Alcolapia grahami, a small cichlid fish of Lake Magadi, Kenya lives in one of the most challenging aquatic environments on earth, characterized by very high alkalinity, unusual water chemistry, and extreme O2, ROS, and temperature regimes. In contrast to most fishes which live at temperatures substantially lower than the 36-40 degrees C of mammals and birds, an isolated population (South West Hot Springs, SWHS) of Magadi tilapia thrives in fast flowing hotsprings with daytime highs of 43 degrees C and night-time lows of 32 degrees C. Another population (Fish Springs Lagoon, FSL) lives in a lagoon with fairly stable daily temperatures (33-36 degrees C). The upper critical temperatures (Ctmax) of both populations are very high; moreover the SWHS tilapia exhibit the highest Ctmax (45.6 degrees C) ever recorded for a fish. Routine rates of O2 consumption (MO2) measured on site, together with MO2 and swimming performance at 25, 32, and 39 degrees C in the laboratory, showed that the SWHS tilapia exhibited the greatest metabolic performance ever recorded in a fish. These rates were in the basal range of a small mammal of comparable size, and were all far higher than in the FSL fish. The SWHS tilapia represents a bellwether organism for global warming. PMID- 27257104 TI - The decision to germinate is regulated by divergent molecular networks in spores and seeds. AB - Dispersal is a key step in land plant life cycles, usually via formation of spores or seeds. Regulation of spore- or seed-germination allows control over the timing of transition from one generation to the next, enabling plant dispersal. A combination of environmental and genetic factors determines when seed germination occurs. Endogenous hormones mediate this decision in response to the environment. Less is known about how spore germination is controlled in earlier-evolving nonseed plants. Here, we present an in-depth analysis of the environmental and hormonal regulation of spore germination in the model bryophyte Physcomitrella patens (Aphanoregma patens). Our data suggest that the environmental signals regulating germination are conserved, but also that downstream hormone integration pathways mediating these responses in seeds were acquired after the evolution of the bryophyte lineage. Moreover, the role of abscisic acid and diterpenes (gibberellins) in germination assumed much greater importance as land plant evolution progressed. We conclude that the endogenous hormone signalling networks mediating germination in response to the environment may have evolved independently in spores and seeds. This paves the way for future research about how the mechanisms of plant dispersal on land evolved. PMID- 27257107 TI - HCV treatment in liver transplantation: timing is the challenge. PMID- 27257106 TI - A two-neuron system for adaptive goal-directed decision-making in Lymnaea. AB - During goal-directed decision-making, animals must integrate information from the external environment and their internal state to maximize resource localization while minimizing energy expenditure. How this complex problem is solved by the nervous system remains poorly understood. Here, using a combined behavioural and neurophysiological approach, we demonstrate that the mollusc Lymnaea performs a sophisticated form of decision-making during food-searching behaviour, using a core system consisting of just two neuron types. The first reports the presence of food and the second encodes motivational state acting as a gain controller for adaptive behaviour in the absence of food. Using an in vitro analogue of the decision-making process, we show that the system employs an energy management strategy, switching between a low- and high-use mode depending on the outcome of the decision. Our study reveals a parsimonious mechanism that drives a complex decision-making process via regulation of levels of tonic inhibition and phasic excitation. PMID- 27257109 TI - [Racemosa hemangioma or Wyburn Mason or Bonnet-Dechaume-Blanc incomplete syndrome]. PMID- 27257108 TI - Vestibular dysfunction in the adult CBA/CaJ mouse after lead and cadmium treatment. AB - OBJECTIVES: The vestibular system allows the perception of position and motion and its dysfunction presents as motion impairment, vertigo and balance abnormalities, leading to debilitating psychological discomfort and difficulty performing daily tasks. Although declines and deficits in vestibular function have been noted in rats exposed to lead (Pb) and in humans exposed to Pb and cadmium (Cd), no studies have directly examined the pathological and pathophysiological effects upon the vestibular apparatus of the inner ear. METHODS: Eighteen young adult mice were exposed through their drinking water (3 mM Pb, 300 uM Cd, or a control treatment) for 10 weeks. Before and after treatment, they underwent a vestibular assessment, consisting of a rotarod performance test and a novel head stability test to measure the vestibulocolic reflex. At the conclusion of the study, the utricles were analyzed immunohistologically for condition of hair cells and nerve fibers. RESULTS: Increased levels of Pb exposure correlated with decreased head stability in space; no significant decline in performance on rotarod test was found. No damage to the hair cells or the nerve fibers of the utricle was observed in histology. CONCLUSIONS: The young adult CBA/CaJ mouse is able to tolerate occupationally relevant Pb and Cd exposure well, but the correlation between Pb exposure and reduced head stability suggests that Pb exposure causes a decline in vestibular function. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 869-876, 2017. PMID- 27257110 TI - [Is there a need for a therapeutic education with patients suffering with open angle glaucoma? Preliminary inquiry regarding knowledge and patient adherence]. AB - PURPOSE: To evaluate the knowledge and compliance of patients with open-angle glaucoma in order to propose an approach by therapeutic education, validated for other chronic pathologies. METHODS: A questionnaire-based interview of all patients in the waiting room of the glaucoma center is performed by the same health care professional. RESULTS: Out of 200 patients, 73% know they will need to be treated throughout their lives and 95% are aware of the risk of blindness in the absence of appropriate treatment. However, 16% respond that they can be cured, and 54% believe that treatment can save their eyesight. Knowledge increases with the length of follow-up of patients at the glaucoma center beyond one year, but the progress is still insufficient in their confidence that treatment can save their eyesight (36% to 57%), and in the decrease in the number of patients who forget their treatment (56% to 30%). CONCLUSION: Cognitive knowledge is insufficient to encourage the patient to comply with treatment. It is necessary to consider therapeutic patient education (TPE) techniques, such as described by WHO, in group and/or individual sessions, aimed at building the patient's confidence that treatment can delay the progression of the disease and blindness, strengthening his/her capacity to properly administer the eye drops, managing his/her treatment and coping with frequent side effects. Within this framework, our knowledge of the patients' representations of their glaucoma and its treatment must improve. PMID- 27257111 TI - [Bulbar conjunctival osseous choristoma in a 9-year-old girl: Clinical and pathological findings]. PMID- 27257112 TI - Small Size at Birth or Abnormal Intrauterine Growth Trajectory: Which Matters More for Child Growth? AB - Small size at birth is linked with lifelong adverse health implications. However, small size is only a proxy for the pathological process of interest, intrauterine growth restriction. We examined the extent to which information on intrauterine growth patterns improved prediction of childhood anthropometry, above and beyond birth weight alone. We obtained fetal weights estimated via serial ultrasound for 478 children in the Scandinavian Successive Small-for-Gestational-Age Births Study (1986-1988). Size at birth was classified using birth weight-for gestational-age z scores and conditional fetal growth z scores (reflecting growth between 25 weeks' gestation and birth) using internal references. Conditional z scores were also expressed as residuals of birth weight z scores. Growth measures were linked with age-5-years anthropometric characteristics using linear regression. In univariable analyses, conditional fetal growth z scores were positively associated with z scores for child height, body mass index, total skinfold thickness, and head circumference (beta = 0.24 (95% confidence interval (CI): 0.18, 0.31), beta = 0.16 (95% CI: 0.09, 0.23), beta = 0.08 (95% CI: 0.01, 0.16), and beta = 0.37 (95% CI: 0.22, 0.52), respectively). However, conditional z scores were highly correlated with birth weight z scores (r = 0.9), and residuals explained minimal additional variation in anthropometric factors (null coefficients; adjusted R(2) increases < 0.01). Information on the intrauterine trajectory through which birth weight was attained provided little additional insight into child growth beyond that obtained from absolute size at birth. PMID- 27257113 TI - Placental Weight and Male Genital Anomalies: A Nationwide Danish Cohort Study. AB - The most consistently reported risk indicators for the male genital anomalies cryptorchidism and hypospadias are prematurity and low birth weight. Placental dysfunction has been hypothesized as a possible underlying cause, and an association between placental weight at birth and hypospadias has been indicated. In a population-based cohort of 388,422 Danish singleton boys born alive (1997 2008), we studied the association between placental weight and cryptorchidism and hypospadias. Missing data were handled with multiple imputation, and we estimated hazard ratios by means of Cox regression models. During follow-up, 1,713 boys were diagnosed with hypospadias and 6,878 with cryptorchidism (3,624 underwent corrective surgery). We observed an association between low placental weight and risk of both genital anomalies. Boys with a placental weight in the lowest decile (<10%) had higher risks of both cryptorchidism (hazard ratio = 1.52, 95% confidence interval: 1.31, 1.76) and hypospadias (hazard ratio = 1.97, 95% confidence interval: 1.59, 2.45) than boys in the reference decile (50.0-59.9%). In conclusion, we found higher risks of both genital malformations in boys born with a low placental weight. The relationship seemed stronger for hypospadias than for cryptorchidism. Taken together, our data support a role for placental dysfunction in the etiology of these anomalies. PMID- 27257115 TI - Time-Dependent Risk of Cancer After a Diabetes Diagnosis in a Cohort of 2.3 Million Adults. AB - Using a time-dependent approach, we investigated all-site and site-specific cancer incidence in a large population stratified by diabetes status. The study analyzed a closed cohort comprised of Israelis aged 21-89 years, enrolled in a health fund, and followed from 2002 to 2012. Adjusting for age, ethnicity, and socioeconomic status, we calculated hazard ratios for cancer incidence using Cox regression separately for participants with prevalent and incident diabetes; the latter was further divided by time since diabetes diagnosis. Of the 2,186,196 individuals included in the analysis, 159,104 were classified as having prevalent diabetes, 408,243 as having incident diabetes, and 1,618,849 as free of diabetes. In both men and women, diabetes posed an increased risk of cancers of the liver, pancreas, gallbladder, endometrium, stomach, kidney, brain (benign), brain (malignant), colon/rectum, lung (all, adenocarcinoma, and squamous cell carcinoma), ovary, and bladder, as well as leukemia, multiple myeloma, non Hodgkin lymphoma, and breast cancer in postmenopausal women. No excess risk was observed for breast cancer in premenopausal women or for thyroid cancer. Diabetes was associated with a reduced risk of prostate cancer. Hazard ratios for all-site and site-specific cancers were particularly elevated during the first year following diabetes diagnosis. The findings of this large study with a time dependent approach are consistent with those of previous studies that have observed associations between diabetes and cancer incidence. PMID- 27257116 TI - The Authors Reply. PMID- 27257114 TI - Neighborhood Socioeconomic Status and Cognitive Function in Late Life. AB - Neighborhood socioeconomic status (NSES) is associated with cognitive function, independently of individual demographic, health, and socioeconomic characteristics. However, research has been largely cross-sectional, and mechanisms of the association are unknown. In 1992-1993, Cardiovascular Health Study participants (n = 3,595; mean age = 74.8 years; 15.7% black) underwent cognitive testing and magnetic resonance imaging of white matter hyperintensities (WMH), and their addresses were geocoded. NSES was calculated using 1990 US Census data (block groups; 6 measures of wealth, education, and occupation). The Modified Mini-Mental State Examination (3MS) was used to assess general cognition, and the Digit Symbol Substitution Test (DSST) was used to assess speed of processing annually for 6 years. Associations of race-specific NSES tertiles with 3MS, DSST, and WMH were estimated using linear mixed-effects models accounting for geographic clustering, stratified by race, and adjusted for demographic, health, and individual socioeconomic status (education, income, lifetime occupational status) variables. In fully adjusted models, higher NSES was associated with higher 3MS scores in blacks (mean difference between highest and lowest NSES = 2.4 points; P = 0.004) and whites (mean difference = 0.7 points; P = 0.02) at baseline but not with changes in 3MS over time. NSES was marginally associated with DSST and was not associated with WMH. Adjustment for WMH did not attenuate NSES-3MS associations. Associations of NSES with cognition in late adulthood differ by race, are not explained by WMH, and are evident only at baseline. PMID- 27257117 TI - Re: "Job Strain and the Cortisol Diurnal Cycle in MESA: Accounting for Between- and Within-Day Variability". PMID- 27257118 TI - Innovation or 'Inventions'? The conflict between latent assumptions in marine aquaculture and local fishery. AB - Recent European policy highlights the need to promote local fishery and aquaculture by means of innovation and joint participation in fishery management as one of the keys to achieve the sustainability of our seas. However, the implicit assumptions held by the actors in the two main groups involved - innovators (scientists, businessmen and administration managers) and local fishermen - can complicate, perhaps even render impossible, mutual understanding and co-operation. A qualitative analysis of interviews with members of both groups in the Valencian Community (Spain) reveals those latent assumptions and their impact on the respective practices. The analysis shows that the innovation narrative in which one group is based and the inventions narrative used by the other one are rooted in two dramatically different, or even antagonistic, collective worldviews. Any environmental policy that implies these groups should take into account these strong discords. PMID- 27257119 TI - Simultaneous separation and rapid determination of spironolactone and its metabolite canrenone in different pharmaceutical formulations and urinary matrices by capillary zone electrophoresis. AB - The aim of this study was to develop a novel, sensitive, precise, simple, and rapid capillary zone electrophoresis method for the quality control of spironolactone in three different formulation types and a rapid simultaneous determination of the content of spironolactone and canrenone in urine samples using fluocinonide as an internal standard. After optimization of separation conditions, the electrolyte solution was the pH 5.5, 20 mM phosphate buffer containing 4.5 g/L sulfated-beta-cyclodextrin, 15 kV of electric filed across the capillary applied at 25 degrees C. A diode array detector was used, and the detection wavelength was 260 nm. Under optimum conditions, good linearity was achieved with correlation coefficients from 0.9976 to 0.9997. Detection limits were 0.56 and 0.20 MUg/mL, and the quantitation limits were 1.87 and 0.67 MUg/mL, respectively. Excellent accuracy and precision were obtained. Recoveries of the analytes varied from 100.8 to 103.1%. The results indicated that baseline separation of analytes was obtained and this method was suitable for quantitative determination of spironolactone in pharmaceutical preparations and rapid simultaneous determination of the content of spironolactone and its major metabolite canrenone in urine samples. PMID- 27257120 TI - The Natural Course of Intermittent Exotropia over a 3-year Period and the Factors Predicting the Control Deterioration. AB - The natural course of intermittent exotropia and the factors affecting its control has been unclear. We aim to report the natural course of our cohort of 117 Chinese children with intermittent exotropia and to identify baseline parameters that may have predictive value in the control deterioration of the disease. The visual acuity, spherical equivalent, compliance to orthoptic exercise, angle of deviation fusional convergence parameters and Newcastle Control Score were recorded for all children at baseline and at 3 years apart. Patients were divided into two groups according to the change in control over the 3 years: group 1 included patients who had no deterioration or had improvement in disease control; and group 2 were those who had deteriorated control or had undergone surgery. There were 77 patients (66%) in group 1 and 40 (34%) patients in group 2. Comparing the baseline parameters of the two groups, group 1 had statistically significantly smaller angle of deviation, larger fusional reserve, larger fusional recovery, and higher fusional reserve ratio (p < 0.05). Other baseline parameters were similar between the two groups. The baseline fusional parameters may have predictive value in determining the control of intermittent exotropia. PMID- 27257121 TI - Seed Selection by the Harvester Ant Pogonomyrmex rugosus (Hymenoptera: Formicidae) in Coastal Sage Scrub: Interactions With Invasive Plant Species. AB - Harvester ants can be the dominant seed predators on plants by collecting and eating seeds and are known to influence plant communities. Harvester ants are abundant in coastal sage scrub (CSS), and CSS is frequently invaded by several exotic plant species. This study used observations of foraging and cafeteria style experiments to test for seed species selection by the harvester ant Pogonomyrmex rugosus Emery (Hymenoptera: Formicidae) in CSS. Analysis of foraging behavior showed that P. rugosus carried seeds of exotic Erodium cicutarium (L.) and exotic Brassica tournefortii (Gouan) on 85 and 15% of return trips to the nest (respectively), and only a very few ants carried the native seeds found within the study areas. When compared with the availability of seeds in the field, P. rugosus selected exotic E. cicutarium and avoided both native Encelia farinosa (Torrey & A. Gray) and exotic B. tournefortii. Foraging by P. rugosus had no major effect on the seed bank in the field. Cafeteria-style experiments confirmed that P. rugosus selected E. cicutarium over other available seeds. Native Eriogonum fasciculatum (Bentham) seeds were even less selected than E. farinosa and B. tournefortii. PMID- 27257122 TI - All-Optical Fiber Hanbury Brown &Twiss Interferometer to study 1300 nm single photon emission of a metamorphic InAs Quantum Dot. AB - New optical fiber based spectroscopic tools open the possibility to develop more robust and efficient characterization experiments. Spectral filtering and light reflection have been used to produce compact and versatile fiber based optical cavities and sensors. Moreover, these technologies would be also suitable to study N-photon correlations, where high collection efficiency and frequency tunability is desirable. We demonstrated single photon emission of a single quantum dot emitting at 1300 nm, using a Fiber Bragg Grating for wavelength filtering and InGaAs Avalanche Photodiodes operated in Geiger mode for single photon detection. As we do not observe any significant fine structure splitting for the neutral exciton transition within our spectral resolution (46 MUeV), metamorphic QD single photon emission studied with our all-fiber Hanbury Brown &Twiss interferometer could lead to a more efficient analysis of entangled photon sources at telecom wavelength. This all-optical fiber scheme opens the door to new first and second order interferometers to study photon indistinguishability, entangled photon and photon cross correlation in the more interesting telecom wavelengths. PMID- 27257123 TI - Insights into cardiac alterations after pre-eclampsia: an echocardiographic study. AB - OBJECTIVES: To investigate cardiovascular (CV) performance status several years after early-onset (EO) or late-onset (LO) pre-eclampsia (PE), using echocardiography to assess myocardial strain and left ventricular (LV) torsional mechanics and ventricular-arterial coupling (VAC). METHODS: Thirty non-pregnant women with a previous singleton pregnancy complicated by EO-PE, 30 who had experienced LO-PE and 30 controls underwent echocardiography with two-dimensional (2D) speckle tracking between 6 months and 4 years after delivery and their findings were compared. All women were free from CV risk factors. VAC was defined as the ratio between aortic elastance (Ea) and LV end-systolic elastance (Ees). RESULTS: Women in the EO-PE group showed a persistent subclinical impairment in LV systole and a slight alteration in right ventricular function, with reductions in LV 2D strain (circumferential, radial and longitudinal) and right ventricular 2D strain and impairment of LV torsional mechanics, when compared both with women in the LO-PE group and with healthy controls. Although VAC was within the normal range in the whole study cohort, its individual components Ea and Ees were significantly altered more often in the EO-PE group than in both the LO-PE group and controls. All parameters investigated (except right ventricular 2D strain) were associated independently with gestational age at the time of diagnosis of PE. CONCLUSIONS: Women with a history of EO-PE are more likely to have subclinical impairment of systolic biventricular function than are those with a history of LO-PE and controls. The components of VAC (Ea and Ees) show subclinical alterations which are more significant in women with a history of EO PE than in those with a history of LO-PE and controls, although VAC itself is maintained. Our study supports the use of closer CV monitoring in previously pre eclamptic women, particularly those in whom PE was preterm. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27257124 TI - CYP gene family variants as potential protective factors in drug addiction in Han Chinese. AB - BACKGROUND: There is growing evidence that genetic factors also contribute to drug addiction. The human cytochrome P450 has shown special interest because of pharmacokinetic variation in different individuals and populations, which is largely determined by the relevant genes. The present study aimed to investigate the polymorphism of the CYP/addicts relationship. METHODS: We genotyped 13 tag single-nucleotide polymorphisms (tSNPs) from three genes, including 692 cases and 700 controls. Sequenom MassARRAY RS1000 (Sequenom, Inc., San Diego, CA, USA) was used for SNP genotyping. Statistical analysis of the association between tSNPs and drug addiction was performed using the chi-squared test and SNP Stats software (http://bioinfo.iconcologia.net). RESULTS: The T/T genotype of rs2242480 in CYP3A4 was associated with decreased risk in the recessive model (p = 0.0002). Allele frequency at rs3743484 in CYP1A2 showed significant differences between addicts and controls (p = 0.046; odds ratio = 0.80; 95% confidence interval = 0.65-1.00). In genetic model analyses, the minor C allele of rs3743484 in CYP1A2 was associated with a reduced risk of drug addiction based on analysis using codominant and additive models (p = 0.027 dominant model; p =0.038 additive model). CONCLUSIONS: Our findings show that at allelic and genotypic level polymorphisms in CYP3A4 and CYP1A2 are significantly associated with a reduced risk of drug addiction in X'ian Han Chinese individuals. However, this result needs to be confirmed in additional studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27257125 TI - A comparison of institutional review board professionals' and patients' views on consent for research on medical practices. AB - BACKGROUND/AIMS: In the context of research on medical practices, which includes comparative effectiveness research and pragmatic clinical trials, empirical studies have begun to raise questions about the extent to which institutional review boards' interpretations and applications of research regulations align with patients' values. To better understand the similarities and differences between these stakeholder groups, we compare and contrast two surveys: one of institutional review board professionals and one of patients, which examine views on consent for research on medical practices. METHODS: We conducted online surveys of two target populations between July 2014 and March 2015. We surveyed 601 human subjects research professionals out of 1500 randomly selected from the Public Responsibility in Medicine and Research membership list (40.1% response rate), limiting analysis to 537 respondents who reported having had institutional review board experience. We also surveyed 120 adult patients out of 225 approached at subspecialty clinics in Spokane, Washington (53.3% response rate). Our survey questions probed attitudes about consent in the context of research on medical practices using medical record review and randomization. The patient survey included three embedded animated videos to explain these concepts. RESULTS: A majority of institutional review board professionals distinguished between consent preferences for medical record review and randomization, ranked clinicians as the least preferred person to obtain participant consent (54.6%), and viewed written or verbal permission as the minimum acceptable consent approach for research on medical practices using randomization (87.3%). In contrast, most patients had similar consent preferences for research on medical practices using randomization and medical record review, most preferred to have consent conversations with their doctors rather than with researchers for studies using randomization (72.6%) and medical record review (67.0%), and only a few preferred to see research involving randomization (16.8%) or medical record review (13.8%) not take place if obtaining written or verbal permission would make the research too difficult to conduct. Limitations of our post hoc analysis include differences in framing, structure, and language between the two surveys and possible response bias. CONCLUSION: Our findings highlight a need to identify appropriate ways to integrate patient preferences into prevailing regulatory interpretations as institutional review boards increasingly apply research regulations in the context of research on medical practices. Dialogue between institutional review boards and research participants will be an important part of this process and should inform future regulatory guidance. PMID- 27257128 TI - Morphology of the Bearded Seal (Erignathus barbatus) Muscular-Vibrissal Complex: A Functional Model for Phocid Subambient Pressure Generation. AB - Bearded seals possess a broad muscular snout with large mystacial vibrissal fields that are involved in tactile sensation and prey identification. Although the microstructure of bearded seal vibrissae and their feeding performance have been investigated their orofacial morphology has not. Such morphological studies are important to understand the underlying mechanisms of feeding performance and to test proposed functional hypotheses. Therefore, the facial musculature was examined in bearded seals to test functional hypotheses regarding feeding performance. The orofacial musculature is composed primarily of three enlarged muscular layers, the M. levator nasolabialis, M. orbicularis oris, and M. buccinatorius (superficial), M. maxillonasolabialis (intermediate), and the M. lateralis nasi and M. dilator nasi (deep). The expansion of these muscles, the three dimensionality of the entire muscular array, the soft tissue insertions, and constant volume fit the model of a muscular hydrostat, and explains the detailed and varied mobility of their snout. An anastomosing network of CN VII innervates these facial muscles. The disproportionately large infraorbital nerve of CN V courses toward the snout and divides into numerous branches that penetrate the external capsule of every Follicle Sinus-Complex. The anatomical evidence support that the M. orbicularis oris, M. buccinatorius, and M. maxillonasolabialis form a robust lateral lip complex that can occluded lateral gape during subambient pressure generation. The rostral portion of the M. orbicularis oris, M. dilator nasi, and M. mentalis function to pursue the rostral lips to form a circular aperture important for projecting steep pressure gradients rostral to the lips for prey acquisition. Anat Rec, 299:1043-1053, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27257127 TI - The Utility of Limb Symmetry Indices in Return-to-Sport Assessment in Patients With Bilateral Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: The incidence of contralateral anterior cruciate ligament (ACL) injury after ACL reconstruction (ACLR) is high. Often, return-to-sport (RTS) tests of strength and functional hopping rely on limb symmetry indices (LSIs) to identify deficits, although the utility of these measures in athletes with bilateral ACL injuries is unknown. PURPOSE/HYPOTHESIS: The aim of this study was to investigate if LSIs used as RTS criteria in female patients after unilateral ACLR were appropriate for female patients with bilateral ACL involvement. The hypothesis tested was that asymmetries with traditional LSI measures would be present in a population after unilateral ACLR but would not be present in a population with bilateral ACLR due to the lack of a healthy internal control limb. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A total of 45 female subjects were classified into 3 groups: after second (contralateral) ACLR (ACLR-B; n = 15); after primary unilateral ACLR (ACLR-U; n = 15); and uninjured controls (CTRL; n = 15). After being cleared for RTS, each subject completed a single-legged hop for distance (SLHD), triple hop for distance (THD), and triple-crossover hop for distance (CHD) test, in addition to an isometric quadriceps strength test on both limbs. Means and LSI ([involved limb/uninvolved limb] * 100) were calculated for each test. Limb symmetry deficits were defined by LSI <90%. RESULTS: Analysis of functional hop testing revealed a side * group interaction for SLHD (P = .001), THD (P = .019), and CHD (P = .04). Side-to-side differences were found in the ACLR-U group for all hop tests (P = .001-.003) and in the ACLR-B group for SLHD (P = .002) and THD tests (P = .024). No side-to side differences were seen in the CTRL group (P > .05). A side * group interaction was found for isometric quadriceps strength (P = .006), with lower LSI seen in the ACLR-U group (81% +/- 17.6%) compared with the CTRL group (102.2% +/- 10.8%) and the ACLR-B group (95.6% +/- 24.9%). Although no interaction was seen, side-to side differences were noted in the THD in the ACLR-U group (P = .013) and ACLR-B group (P = .024) and in the CHD in the ACLR-U group (P = .001). Despite absence of an LSI deficit, bilateral peak quadriceps strength in the ACLR-B group was comparable to the involved limb of the ACLR-U group and less than in the CTRL group (P = .012). CONCLUSION: Both the ACLR-U and the ACLR-B groups demonstrated side-to-side deficits during functional hop tests; however, these deficits were not identified according to the clinically accepted LSI values of >=90%, calling into question the efficacy of current RTS criteria. At the time of RTS, only individuals in the ACLR-U group demonstrated an altered LSI in quadriceps strength. Significantly lower quadriceps strength of both limbs in the ACLR-B group was seen compared with the CTRL group, despite no LSI deficits in quadriceps strength. Current use of LSIs during strength and performance tests may not be an appropriate means of identifying residual deficits in female patients after bilateral ACLR at time of RTS. Furthermore, a better indicator of strength performance in this population may need to include a comparison of strength performance values to the normative values of healthy controls. PMID- 27257129 TI - Development and validation of a liquid chromatography with tandem mass spectrometry method for the determination of isomangiferin in rat plasma with application to a preclinical pharmacokinetic study. AB - A sensitive and specific liquid chromatography with tandem mass spectrometry method was firstly developed for the measurement of isomangiferin in rat plasma. Chloramphenicol was selected as the internal standard. Sample preparation was carried out through a simple one-step protein precipitation procedure with methanol. Negative electrospray ionization was performed using multiple reaction monitoring mode with transitions of m/z 421.1/301.1 for isomangiferin, and 321.1/151.9 for chloramphenicol. The calibration curve was linear over the range of 0.1-600 ng/mL, with a lower limit of quantification at 0.1 ng/mL. The intra- and interday precisions (relative standard deviation) were no more than 8.2% and accuracies (relative error) were within the range of -8.4 to 2.2%. The recovery, matrix effect and stability under different conditions were all proved acceptable. The validated method has been successfully applied to a preclinical pharmacokinetic study of isomangiferin in rats for the first time. PMID- 27257130 TI - Absolute number of parvicellular and magnocellular neurons in the red nucleus of the rat midbrain: a stereological study. AB - The absolute number of parvicellular and magnocellular neurons in the red nucleus was estimated using design-based stereological counting methods and systematic random sampling techniques. Six young adult male rats, and a complete set of serial 40-MUm glycolmethacrylate sections for each rat, were used to quantify neuronal numbers. After a random start, a systematic subset (i.e. every third) of the serial sections was used to estimate the total volume of the red nucleus using Cavalieri's method. The same set of sampled sections was used to estimate the number of neurons in a known subvolume (i.e. the numerical density Nv ) by the optical disector method. Multiplication of the total volume by Nv yielded the absolute number of neurons. It was found that the right red nucleus consisted, on average, of 8400 parvicellular neurons (with a coefficient of variation of 0.16) and 7000 magnocellular neurons (0.12). These total neuronal numbers provide important data for the transfer of information through these nuclei and for species comparisons. PMID- 27257131 TI - The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC. AB - INTRODUCTION: Predictive biomarkers of mesenchymal-to-epithelial transition factor (MET)-targeted therapy remain elusive. Since the discovery of the MNNG HOS Transforming gene (MET) exon 14 mutation, it has been found to have the best potential to become one precise biomarker for MET-targeted therapy. Here, we present the unique characteristics of MET exon 14 mutations in Chinese patients with NSCLC. METHODS: A total of 1296 patients with NSCLC were screened for MET exon 14 mutations. Next-generation sequencing was performed on the DNA of 968 patients and Sanger sequencing was conducted on complementary DNA of the other 328 patients. Immunohistochemical analysis and fluorescence in situ hybridization were also performed on all specimens. RESULTS: Twelve patients had MET exon 14 mutations. These accounted for only 0.9% of adenocarcinoma. Thus, the mutations were present at less than half the frequency of their occurrence in Western patients (0.9% versus 3% in Chinese and white patients, respectively, chi(2) = 15.1, p < 0.001). Samples from six patients with MET exon 14 mutations were analyzed using immunohistochemical analysis and fluorescence in situ hybridization. We found no significant relationships among the mutation, MET amplification, and MET overexpression. In two patients who received crizotinib, only one patient (who exhibited MET amplification) experienced a partial response; the progression-free survival was 9 months. However, it remains unclear whether the sensitivity of this patient to crizotinib was conferred by the MET exon 14 mutation per se or by MET amplification. In the other patient with concomitant MET exon 14 skipping and KRAS G12D mutation, the disease progressed in only 1 month. CONCLUSIONS: MET exon 14 mutation per se may not be sufficiently robust for use in defining a subset of NSCLCs. Further research on MET exon 14 mutations, MET amplification, and MET overexpression is required. Maybe a panel of biomarkers will be necessary in the future. PMID- 27257132 TI - L718Q Mutation as New Mechanism of Acquired Resistance to AZD9291 in EGFR-Mutated NSCLC. PMID- 27257133 TI - Heterogeneity of EGFR Aberrations and Correlation with Histological Structures: Analyses of Therapy-Naive Isogenic Lung Cancer Lesions with EGFR Mutation. AB - INTRODUCTION: EGFR gene somatic mutation is reportedly homogeneous. However, there are few data regarding the heterogeneity of expression of mutant EGFR protein and EGFR gene copy number, especially in extrathoracic lesions. These types of data may enhance our understanding of the biology of EGFR-mutated lung cancer and our understanding of the heterogeneous response patterns to EGFR TKIs. METHODS: An 81-year-old never-smoking female with lung adenocarcinoma could not receive any systemic therapy because of her poor performance status. After her death, 15 tumor specimens from different sites were obtained by autopsy. Expression of mutant EGFR protein and EGFR gene copy numbers were assessed by immunohistochemical analysis and by silver in situ hybridization, respectively. Heterogeneity in these EGFR aberrations was compared between metastatic sites (distant versus lymph node) or histological structures (micropapillary versus nonmicropapillary). RESULTS: All lesions showed positive staining for mutant EGFR protein, except for 40% of the papillary component in one of the pulmonary metastases (weak staining below the 1+ threshold). Expression of mutant-specific EGFR protein, evaluated by H-score, was significantly higher in the micropapillary components than in the nonmicropapillary components (Mann-Whitney U test, p = 0.014). EGFR gene copy number was quite different between lesions but not correlated with histological structure or metastatic form. However, EGFR gene copy numbers were similar between histological structures in each lesion. CONCLUSION: These data indicate that expression of EGFR mutant protein and EGFR gene copy number do not change as a consequence of tumor progression. This also justifies using the biopsy specimens from metastases as a surrogate for primary tumors. PMID- 27257134 TI - Thoracoscopic Lobectomy Produces Long-Term Survival Similar to That with Open Lobectomy in Cases of Non-Small Cell Lung Carcinoma: A Propensity-Matched Analysis Using a Population-Based Cancer Registry. AB - BACKGROUND: There is a lack of large, prospective, randomized studies comparing thoracoscopic and open lobectomy in terms of long-term survival in the setting of NSCLC. Additionally, large case series evaluating the issue are limited. Until now, whether thoracoscopic lobectomy entails a long-term survival benefit compared with open lobectomy not been determined. METHODS: Data were obtained from the National Health Insurance Research Database published in Taiwan. We included patients treated with open lobectomy or thoracoscopic lobectomy. In this retrospective review, the clinicopathologic characteristics of 5222 patients with lung cancer during the period 2004-2010 were analyzed. Patients were stratified according to clinical stage. Overall survival (OS) was compared between patients treated with open and those treated with thoracoscopic lobectomy and was also compared between patients in the three different clinical stages. Propensity matching analysis and multivariate analysis were performed. RESULTS: Open lobectomy was performed on 3058 patients (58.6%) and thoracoscopic lobectomy on 2164 (41.4%). Propensity matching produced 1848 patients in each group. The 1 year, 3-year, and 5-year OS rates for propensity-matched patients treated with open lobectomy were 93.4%, 79.3%, and 65.5%, respectively. The 1-year, 3-year, and 5-year OS rates for propensity-matched patients treated with thoracoscopic lobectomy were 94.1%, 80.9%, and 68.7%, respectively. The difference was not statistically significant. In multivariate analysis, surgical resection (open versus thoracoscopic) was not an independent prognostic factor. CONCLUSIONS: This propensity-matched study suggests that open and thoracoscopic lobectomy are associated with similar long-term survival in the setting of lung cancer. Thoracoscopic lobectomy is an acceptable surgical treatment of lung cancer. PMID- 27257135 TI - Bladder Preservation Therapy: A Review of the Literature and Future Directions. AB - Trimodal bladder preservation therapy (ie, transurethral resection followed by chemoradiotherapy) may be an acceptable treatment alternative to radical cystectomy with urinary diversion in the carefully selected patient with muscle invasive bladder cancer. Although no head-to-head randomized controlled trials have been performed, large retrospective cohort reviews and observational data analyses suggest comparable oncologic outcomes in select patients with the additional benefit of maximizing quality of life and maintaining the patient's native bladder. In this review, we discuss the evolution and clinical outcomes of bladder preservation therapy, highlighting its role in the contemporary management of muscle invasive bladder cancer. PMID- 27257136 TI - Maternal plasma mRNA species in fetal heart defects: a potential for molecular screening. AB - OBJECTIVE: To verify the hypothesis that aberrant placental mRNA genes related to cardiogenesis can be detected in maternal plasma at the second trimester of pregnancy. METHODS: NanoString technology was used to identify aberrant genes, comparing 39 women carrying a fetus with a congenital heart defect (CHD) to 31 controls at 19-24 weeks of gestation. The genes with differential expression were subsequently tested using real time polymerase chain reaction. Linear discriminant analysis (LDA) was used to combine all the mRNA species with discriminant ability for CHD. A multivariable receiver operating characteristic (ROC) curve having the estimated discriminant score as an explanatory variable was generated. RESULTS: Six genes with differential expression, namely FALZ, PAPP A, PRKACB, SAV1, STK4 and TNXB2, were found. The ROC curve yielded a detection rate of 66.7% at a false positive rate of 10%. A higher discriminant score (>75(th) centile) was reached for 14 CHD cases (82.4%) and only 1 control (5.8%). Two cases (11.8%) of heart rhythm disorders also yielded a discriminant score value >75(th) centile. CONCLUSION: These data represent a step forward in the screening of CHDs. Additional studies are needed to detect more mRNAs with discriminant ability and to move the first trimester screening. PMID- 27257137 TI - Chronic Exposure to Bisphenol A Exacerbates Dental Fluorosis in Growing Rats. AB - Enamel defects resulting from environmental conditions and way of life are public health concerns because of their high prevalence. Because their etiology is unclear, the aim of this study was to analyze the various forms of enamel hypomineralization, and to characterize the genes involved in this process to determine the mechanisms involved in disruptions of amelogenesis. We used bisphenol A (BPA) and fluoride as models; both are commonly encountered in human populations and utilized in dentistry. Wistar rats were chronically exposed to 5 MUg/kg/day BPA from day 1 of gestation to day 65 after birth (P65) and 5 mM fluoride from P21 to P65. Resulting enamel defects were comparable to the human enamel pathologies molar incisor hypomineralization (MIH) and dental fluorosis (DF) respectively, and were more severe in rats exposed to both agents than to each agent alone. Large-scale transcriptomic analysis of dental epithelium showed a small group of genes the expression of which was affected by exposure to BPA or NaF. Among the most modulated, many are directly involved in amelogenesis (Amelx, Enam, Klk4, Mmp12, Slc26a4, and Slc5a8), and can be regrouped as forming the "hypomineralization enameloma." Each of these gene expression perturbations may contribute to enamel defects. Exposure to BPA weakens enamel, making it more prone to generate frequent mineralization defects MIH and DF. Our study identifies hypomineralization genes that may enable the use of dental enamel as an early marker of exposure to environmental toxicants because of its unique ability to retrospectively record ameloblast pathophysiology. (c) 2016 American Society for Bone and Mineral Research. PMID- 27257139 TI - Interface strain in vertically stacked two-dimensional heterostructured carbon MoS2 nanosheets controls electrochemical reactivity. AB - Two-dimensional (2D) materials offer numerous advantages for electrochemical energy storage and conversion due to fast charge transfer kinetics, highly accessible surface area, and tunable electronic and optical properties. Stacking of 2D materials generates heterogeneous interfaces that can modify native chemical and physical material properties. Here, we demonstrate that local strain at a carbon-MoS2 interface in a vertically stacked 2D material directs the pathway for chemical storage in MoS2 on lithium metal insertion. With average measured MoS2 strain of ~0.1% due to lattice mismatch between the carbon and MoS2 layers, lithium insertion is facilitated by an energy-efficient cation-exchange transformation. This is compared with low-voltage lithium intercalation for unstrained MoS2. This observation implies that mechanical properties of interfaces in heterogeneous 2D materials can be leveraged to direct energetics of chemical processes relevant to a wide range of applications such as electrochemical energy storage and conversion, catalysis and sensing. PMID- 27257138 TI - Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7. AB - The design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we report the crystal structure of a stapled bicyclic peptide inhibitor G7-B1 in complex with the Grb7 SH2 domain. This revealed an unexpected binding mode of the peptide, in which the staple forms an alternative contact with the surface of the target protein. Based on this structural information, we designed a new series of bicyclic G7 peptides that progressively constrain the starting peptide, to arrive at the G7-B4 peptide that binds with an approximately 2-fold enhanced affinity to the Grb7-SH2 domain (KD = 0.83 MUM) compared to G7-B1 and shows low affinity binding to Grb2-, Grb10- and Grb14-SH2 domains (KD > 100 MUM). Furthermore, we determined the structure of the G7-B4 bicyclic peptide in complex with the Grb7-SH2 domain, both before and after ring closing metathesis to show that the closed staple is essential to the target interaction. The G7-B4 peptide represents an advance in the development of Grb7 inhibitors and is a classical example of structure aided inhibitor development. PMID- 27257140 TI - Mechanisms involved in reproductive toxicity caused by nickel nanoparticle in female rats. AB - Nickel nanoparticles (Ni NPs) are associated with reproductive toxicity. However, the mechanisms of reproductive toxicity are unclear. Our goal was to explore further reproductive toxicity induced by nickel nanoparticle and mechanisms involved in this process, including the role of oxidative stress and apoptosis. According to the one-generation reproductive toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including ultrastructural, reactive oxygen species (ROS), oxidant and antioxidant enzymes, and cell apoptosis-related factors. Ultrastructural results of ovaries showed mitochondrion swelling, disappearance of mitochondrial cristae, and enlargement of the endoplasmic reticulum in the exposure groups. NiNPs had significantly decreased the activity of SOD and CAT, and had increased the levels of ROS, MDA, and NO in comparison with the control groups. The mRNA expressions of caspase-3, caspase-8, and caspase-9 and the expressions of Fas, Cyt c, Bax, and Bid protein on the ovaries significantly increased. At the same time, the expressions of Bcl 2 protein were significantly decreased. Based on these results, oxidative stress and cell apoptosis may play the important roles in inducing reproductive toxicity after NiNPs treatment. (c) 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1674 1683, 2016. PMID- 27257141 TI - Antibody validation and scoring guidelines for ABCG2 immunohistochemical staining in formalin-fixed paraffin-embedded colon cancer tissue. AB - Overexpression of the ATP-dependent drug efflux pump ABCG2 is a major molecular mechanism of multidrug resistance in cancer and might be a predictive biomarker for drug response. Contradictory results have been reported for immunohistochemical studies of ABCG2 protein expression in colorectal cancer (CRC), probably because of the use of different antibodies and scoring approaches. In this study, we systematically studied six commercially available anti-ABCG2 antibodies, using cell lines with up-regulation of ABCG2, and selected one antibody for validation in CRC tissue. Furthermore, we established scoring guidelines for ABCG2 expression based on the clinically used guidelines for HER2 immunohistochemistry assessment in gastric cancer. The guidelines provide a semi quantitative measure of the basolateral membrane staining of ABCG2 and disregard the apical membrane staining and the cytoplasmic signal. Intra-tumor heterogeneity in ABCG2 immunoreactivity was observed; however, statistical analyses of tissue microarrays (TMAs) and the corresponding whole sections from primary tumors of 57 metastatic CRC patients revealed a strong positive correlation between maximum TMA scores and whole sections, especially when more than one core was used. In conclusion, here, we provide validated results to guide future studies on the associations between ABCG2 immunoreactivity in tumor cells and the benefits of chemotherapeutic treatment in patients with CRC. PMID- 27257142 TI - Phantom study quantifying the depth performance of a handheld magnetometer for sentinel lymph node biopsy. AB - PURPOSE: The use of a magnetic nanoparticle tracer and handheld magnetometer for sentinel lymph node biopsy (SLNB) was recently introduced to overcome drawbacks associated with the use of radioisotope tracers. Unlike the gamma probe, the used magnetometers are not only sensitive to the tracer, but also the diamagnetic human body. This potentially limits the performance of the magnetometer when used clinically. METHODS: A phantom, mimicking the magnetic and mechanical properties of the human axilla, was constructed. The depth performance of two current generation magnetometers was evaluated in this phantom. LN-phantoms with tracer uptake ranging from 5 to 500MUg iron were placed at clinically relevant depths of 2.5, 4 and 5.5cm. Distance-response curves were obtained to quantify the depth performance of the probes. RESULTS: The depth performance of both probes was limited. In the absence of diamagnetic material and forces on the probe (ideal conditions) a LN-phantom with high uptake (500MUg iron) could first be detected at 3.75cm distance. In the phantom, only superficially placed LNs (2.5cm) with high uptake (500MUg iron) could be detected from the surface. The penetration depth was insufficient to detect LNs with lower uptake, or which were located deeper. CONCLUSION: The detection distance of the current generation magnetometers is limited, and does not meet the demands formulated by the European Association for Nuclear Medicine for successful transcutaneous SLN localization. Future clinical trials should evaluate whether the limited depth sensitivity is of influence to the clinical outcome of the SLNB procedure. PMID- 27257143 TI - Heritability and Reversibility of DNA Methylation Induced by in vitro Grafting between Brassica juncea and B. oleracea. AB - Grafting between tuber mustard and red cabbage produced a chimeric shoot apical meristem (SAM) of TTC, consisting of Layers I and II from Tuber mustard and Layer III from red Cabbage. Phenotypic variations, which mainly showed in leaf shape and SAM, were observed in selfed progenies GSn (GS = grafting-selfing, n = generations) of TTC. Here the heritability of phenotypic variation and its association with DNA methylation changes in GSn were investigated. Variation in leaf shape was found to be stably inherited to GS5, but SAM variation reverted over generations. Subsequent measurement of DNA methylation in GS1 revealed 5.29 6.59% methylation changes compared with tuber mustard (TTT), and 31.58% of these changes were stably transmitted to GS5, but the remainder reverted to the original status over generations, suggesting grafting-induced DNA methylation changes could be both heritable and reversible. Sequence analysis of differentially methylated fragments (DMFs) revealed methylation mainly changed within transposons and exon regions, which further affected the expression of genes, including flowering time- and gibberellin response-related genes. Interestingly, DMFs could match differentially expressed siRNA of GS1, GS3 and GS5, indicating that grafting-induced DNA methylation could be directed by siRNA changes. These results suggest grafting-induced DNA methylation may contribute to phenotypic variations induced by grafting. PMID- 27257144 TI - A bio-inspired real-time capable artificial lateral line system for freestream flow measurements. AB - To enhance today's artificial flow sensing capabilities in aerial and underwater robotics, future robots could be equipped with a large number of miniaturized sensors distributed over the surface to provide high resolution measurement of the surrounding fluid flow. In this work we show a linear array of closely separated bio-inspired micro-electro-mechanical flow sensors whose sensing mechanism is based on a piezoresistive strain-gauge along a stress-driven cantilever beam, mimicking the biological superficial neuromasts found in the lateral line organ of fishes. Aiming to improve state-of-the-art flow sensing capability in autonomously flying and swimming robots, our artificial lateral line system was designed and developed to feature multi-parameter freestream flow measurements which provide information about (1) local flow velocities as measured by the signal amplitudes from the individual cantilevers as well as (2) propagation velocity, (3) linear forward/backward direction along the cantilever beam orientation and (4) periodicity of pulses or pulse trains determined by cross-correlating sensor signals. A real-time capable cross-correlation procedure was developed which makes it possible to extract freestream flow direction and velocity information from flow fluctuations. The computed flow velocities deviate from a commercial system by 0.09 m s(-1) at 0.5 m s(-1) and 0.15 m s(-1) at 1.0 m s(-1) flow velocity for a sampling rate of 240 Hz and a sensor distance of 38 mm. Although experiments were performed in air, the presented flow sensing system can be applied to underwater vehicles as well, once the sensors are embedded in a waterproof micro-electro-mechanical systems package. PMID- 27257146 TI - DIAGNOSIS OF ENDOCRINE DISEASE: The diagnostic performance of adrenal biopsy: a systematic review and meta-analysis. AB - OBJECTIVE: To perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy. METHODS: Medline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS: We included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6-11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5-3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively. CONCLUSIONS: Evidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications. PMID- 27257147 TI - Pining for the fjords(1). PMID- 27257145 TI - MANAGEMENT OF ENDOCRINE DISEASE: Imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis. AB - OBJECTIVE: Adrenal masses are incidentally discovered in 5% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses. DESIGN: A systematic review and meta-analysis was conducted. METHODS: We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or (18)F-fluoro deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard. RESULTS: We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n=16), MRI (n=15), and FDG-PET (n=9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with <=10HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers. CONCLUSIONS: Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis. PMID- 27257148 TI - Idiopathic pulmonary fibrosis: an Australian perspective. AB - Idiopathic pulmonary fibrosis is a progressive interstitial lung disease of unknown aetiology with a dismal median survival of 3 years. Patients typically develop progressive dyspnoea and increasing exercise limitation. With a rising incidence and prevalence, an unpredictable disease course and limited treatment options, it is rapidly becoming an important public health concern. To date, lung transplantation has been the sole viable hope for treatment for those who qualify. However, the landscape of idiopathic pulmonary fibrosis management is changing, with the recent emergence of novel pharmacotherapy shown to have a favourable influence on the natural history of this disease. PMID- 27257149 TI - Research misconduct: time for a re-think? AB - The incidence of research misconduct appears to be increasing, drawing attention in the general media and academic literature. Concerns have been expressed about probable under-reporting, harms arising, lack of an agreed international definition, welfare of whistleblowers and the adequacy of the investigation processes and any subsequent sanctions. A fully satisfactory approach to prevention, detection, investigation and adjudication has yet to emerge. While the definition of research misconduct contained in the Australian Code for the Responsible Conduct of Research is comprehensive, universities and other research institutions at times struggle in their task of investigating and adjudicating allegations of research misconduct. A more centralised, independent process of oversight and monitoring of this role played by the universities and institutions would help support those institutions and help maintain community confidence in the research endeavour. PMID- 27257150 TI - Have the 'black clouds' cleared with new residency programme regulations? AB - For decades, residents believed to work harder have been referred to as having a 'black cloud'. Residency training programmes recently instituted changes to improve physician wellness and achieve comparable clinical workload. All Internal Medicine residents in the internship class of 2014 at Columbia were surveyed to assess for the ongoing presence of 'black cloud' trainees. While some residents are still thought to have this designation, they did not have a greater workload when compared to their peers. PMID- 27257152 TI - The Australian and New Zealand regional neurology training survey. AB - There is inequitably poorer access to specialist neurologists in regional areas. Recruitment could be improved if more neurology trainees chose to spend some time at regional training sites, which they currently appear to avoid for unclear reasons. We surveyed neurology advanced trainees to assess their attitudes and perceptions about regional training. Aside from innate geographical challenges, there are concerning negative perceptions of the impact of regional training on future metropolitan employment prospects. Minimisation of bias against regional trainees or even rewarding regional exposure would likely improve regional trainee and subsequent specialist recruitment. PMID- 27257151 TI - Nephrotic syndrome as a complication of chronic graft-versus-host disease after allogeneic haemopoietic stem cell transplantation. AB - Nephrotic syndrome (NS) is a rare complication following allogeneic haemopoietic stem cell transplantation (allo-HSCT), with limited current understanding of its pathogenesis. Here, we describe four cases of NS following allo-HSCT diagnosed at our institutions to identify key clinical and pathological features. In addition, a PubMed search was performed to identify existing reports that were pooled together with our cases for analysis. NS occurred as a late complication following allo-HSCT, with median onset 19.5 months after transplant (range: 3.9 84 months). The most common histopathology observed was membranous nephropathy; however, cases of minimal change disease have also been reported. There is a high incidence of prior extra-renal graft-versus-host disease (GvHD), with all four of our cases and 82% of published cases having prior GvHD. Glucocorticosteroids are the most common treatment, with variable degrees of response. Responses to immunosuppression with calcineurin inhibitors and rituximab have been described in steroid-refractory cases. PMID- 27257153 TI - A case of granulomatosis with polyangiitis: rheumatoid arthritis overlap syndrome presenting as cervical cancer successfully treated with rituximab. PMID- 27257154 TI - Life-threatening hypocalcaemia associated with denosumab in advanced chronic kidney disease. PMID- 27257155 TI - A case of delayed onset pyroglutamic acidosis in the sub-acute setting. PMID- 27257156 TI - Pulmonary hypertension assessment on echocardiography: more than peak tricuspid regurgitation velocity assessment. PMID- 27257157 TI - Author reply. PMID- 27257158 TI - Methamphetamine-triggered Takotsubo syndrome and methamphetamine-associated cardiomyopathy: a continuum? PMID- 27257159 TI - Author reply. PMID- 27257160 TI - Discovery of prenylated flavonoids with dual activity against influenza virus and Streptococcus pneumoniae. AB - Influenza virus neuraminidase (NA) is the primary target for influenza therapeutics. Severe complications are often related to secondary pneumonia caused by Streptococcus pneumoniae (pneumococci), which also express NAs. Recently, a NA-mediated lethal synergism between influenza A viruses and pneumococci was described. Therefore, dual inhibitors of both viral and bacterial NAs are expected to be advantageous for the treatment of influenza. We investigated the traditional Chinese herbal drug sang bai pi (mulberry root bark) as source for anti-infectives. Two prenylated flavonoid derivatives, sanggenon G (4) and sanggenol A (5) inhibited influenza A viral and pneumococcal NAs and, in contrast to the approved NA inhibitor oseltamivir, also planktonic growth and biofilm formation of pneumococci. Evaluation of 27 congeners of 5 revealed a correlation between the degree of prenylation and bioactivity. Abyssinone-V 4' methyl ether (27) inhibited pneumococcal NA with IC50 = 2.18 MUM, pneumococcal growth with MIC = 5.63 MUM, and biofilm formation with MBIC = 4.21 MUM, without harming lung epithelial cells. Compounds 5 and 27 also disrupt the synergism between influenza A virus and pneumococcal NA in vitro, hence functioning as dual acting anti-infectives. The results warrant further studies on whether the observed disruption of this synergism is transferable to in vivo systems. PMID- 27257161 TI - Primary emotional traits in patients with personality disorders. AB - There is a longstanding tradition that connects temperament pathology and personality disorders. Emotions are the major constituents of temperament. In mammals, seven primary emotions have been identified: SEEKING, FEAR, CARE, RAGE, SADNESS/PANIC, LUST and PLAY. The study aimed at exploring the relationship between primary emotions and personality disorders (PDs). Five hundred forty-six patients with different degrees and qualities of personality pathology, admitted to treatment in specialized PD services, were diagnosed according to Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and their primary emotional profiles were assessed by the Affective Neuroscience Personality Scales. The Affective Neuroscience Personality Scales explained 19% of the variance in borderline and avoidant criteria. The DSM-IV PD categories displayed different patterns of association to the primary emotions, e.g. the borderline PD profile suggested low thresholds for RAGE and SADNESS, but on the positive side a propensity for SEEKING. In contrast, the dependent PD profile suggested a low threshold for SADNESS but a high threshold for RAGE and SEEKING. The results are promising for a more coherent and evolution-based overall theory of PDs, and the correlations found in this study indicate testable causal pathways to PDs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27257162 TI - Quantification of sofosbuvir in human serum by liquid chromatography with negative ionization mass spectrometry using the parent peak and its source induced fragment: Application to a bioequivalence study. AB - In the mass spectrometry of sofosbuvir, a new orally administered antihepatitis C drug, a weak peak is detected at the m/z value of the parent ion (m/z 530) as a result of in-source dissociation and current methods to its quantification, is based on monitoring of the parent peak using ultra high-performance liquid chromatography with tandem mass spectrometry. With these methods serum concentration of the drug is quantifiable only up to 4-5 h postdose. However, the fragmentation of the molecule generates a more stable ion at m/z 287 (base peak) with a signal intensity of about tenfold compared to the parent ion. Our study was aimed to improve sensitivity of analysis by acquisition of the m/z value of the daughter ion from which it originated instead of the parent molecule. This novelty allows us to measure serum concentrations of the drug for a longer time postdose and provides more opportunity for pharmacokinetic studies of sofosbuvir. Our method was linear over the concentration range of 2-2560 ng/mL of sofosbuvir in human serum with a limit of quantification of 2 ng/mL compared to 10 ng/mL reported previously. The coefficient variation values of both inter and intraday analysis were less than 13.8%, and the percentage error was less than 6.3. PMID- 27257163 TI - Erratum. PMID- 27257164 TI - Trap placement and attractant choice affect capture and create sex and parity biases in collections of the biting midge, Culicoides sonorensis. AB - Culicoides sonorensis Wirth & Jones (Diptera: Ceratopogonidae) is the primary North American vector of bluetongue virus (BTV), which can cause high morbidity and mortality in ruminant livestock or wildlife. Worldwide, most Culicoides surveillance relies on light (usually UV) traps typically placed near animals or larval development sites. However, the trapping method can cause sex, species and parity biases in collections. We collected C. sonorensis from three dairies in California using suction traps baited with CO2 , UV light or CO2 + UV placed near animals, wastewater ponds, or in fields. Higher numbers of parous females were collected using CO2 + UV traps, although this difference was only significant on one dairy. UV traps were poor at collecting nulliparous females, but the addition of UV to a trap increased the abundance of males in a collection. Traps set in open fields collected significantly higher numbers of males and females than in either of the other two locations. In some cases, there was a significant interaction between the trap type and site. We discuss the limitations of traditional trapping methodologies for C. sonorensis and make suggestions for vector surveillance. PMID- 27257165 TI - Congenital Aural Stenosis: Clinical Features and Long-term Outcomes. AB - The aim of the present study was to comprehensively evaluate the clinical features and long-term outcomes of congenital aural stenosis (CAS). This study presents a retrospective review of patients who underwent meatoplasty for CAS at a tertiary referral hospital from 2008 to 2015. A total of 246 meatoplasty procedures were performed on 232 patients in the present study. We performed multivariate regression analysis. Except in the age < 6 years group, no significant difference was observed among different age groups for cholesteatoma formation, p > 0.05. Except for the stenosis of the external auditory canal (EAC) (>4 mm) group, the other stenosis of EAC groups were not associated with cholesteatoma formation, p > 0.05. Postoperative air-bone gaps (ABG) less than 30 dB occurred in 77.3% (99/128) of the patients, and the Jahrsdoerfer score was associated with postoperative ABG, p < 0.001. The complication rate of CAS was 13.8% (20/144), and males showed a higher risk for postoperative complications (OR, 6.563; 95% CI, 1.268-33.966, p = 0.025). These results indicate that meatoplasty was an effective surgical intervention for CAS, showing a stable hearing outcome with prolonged follow-up. There was no significant difference between the cholesteatoma and no cholesteatoma groups for hearing outcomes, p > 0.05. PMID- 27257166 TI - Femoroacetabular Impingement in Adolescent Athletes: Outcomes of Arthroscopic Management. AB - BACKGROUND: Adolescent athletes with symptomatic femoroacetabular impingement (FAI) may respond well to arthroscopic intervention. PURPOSE: This study reports the outcomes of arthroscopic treatment for symptomatic FAI in adolescents. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Included in this study were 104 consecutive athletes (116 hips) younger than 18 years who underwent arthroscopic correction of symptomatic FAI with a minimum 2-year follow-up. All patients were prospectively assessed with the modified Harris Hip Score (mHHS). Pincer lesions were defined by acetabular overcoverage or retroversion with an accompanying labral injury, and cam lesions were defined by loss of sphericity of the femoral head with associated acetabular articular failure. RESULTS: The average follow-up was 38 months (range, 24-120 months), and the average patient age was 16 years (range, 12-17 years), with 47 male and 57 female patients. There were 67 combined, 33 cam, and 16 pincer lesions. The average improvement on the mHHS was 25 points (average score: 69 preoperatively, 94 postoperatively), with 97% improved and 94% good and excellent results. Athletes returned to their sport after 100 procedures (86%). After 16 procedures, 5 patients were unable to return to sport, 6 chose not to, and 5 had completed their high school athletic careers. There were 2 complications, both transient pudendal nerve neurapraxias, that resolved within 2 weeks. Four patients underwent repeat arthroscopic surgery, and 1 underwent periacetabular osteotomy. CONCLUSION: This study reports favorable outcomes of arthroscopic treatment of FAI among adolescent athletes. A high proportion improved, although only 87% actually returned to their sport. Return to sport may be influenced by factors other than just the success of the procedures. PMID- 27257167 TI - Ultrasound-Guided Injection Therapy of Achilles Tendinopathy With Platelet-Rich Plasma or Saline: A Randomized, Blinded, Placebo-Controlled Trial. AB - BACKGROUND: Achilles tendinopathy (AT) is a common and difficult to treat musculoskeletal disorder. PURPOSE: To examine whether 1 injection of platelet rich plasma (PRP) would improve outcomes more effectively than placebo (saline) after 3 months in patients with AT. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 24 patients with chronic AT (median disease duration, 33 months) were randomized (1:1) to receive either a blinded injection of PRP (n = 12) or saline (n = 12). The primary endpoint was improvement in Victorian Institute of Sports Assessment-Achilles (VISA-A) score at 3 months. Secondary outcomes were pain at rest, pain while walking, pain when tendon was squeezed, ultrasonographic changes in tendon thickness, and color Doppler activity. Patients were informed that they could drop out after 3 months if they were dissatisfied with the treatment. RESULTS: After 3 months, all 24 patients were reassessed (no dropouts). No difference between the PRP and the saline group could be observed with regard to the primary outcome (VISA-A score: mean difference [MD], -1.3; 95% CI, -17.8 to 15.2; P = .868). Secondary outcomes were pain at rest (MD, 1.6; 95% CI, -0.5 to 3.7; P = .137), pain while walking (MD, 0.8; 95% CI, -1.8 to 3.3; P = .544), pain when tendon was squeezed (MD, 0.3; 95% CI, -0.2 to 0.9; P = .208), color Doppler activity (MD, 0.3; 95% CI, -0.2 to 0.8; P = .260), and tendon thickness (MD, 0.8 mm; 95% CI, 0.1 to 1.6 mm; P = .030). After the 3-month follow-up, a large dropout was observed: 75% of patients in the PRP group and 33% in the saline group. CONCLUSION: PRP injection did not result in an improved VISA-A score over a 3-month period in patients with chronic AT compared with placebo. The only secondary outcome demonstrating a statistically significant difference between the groups was change in tendon thickness; this difference indicates that a PRP injection could increase tendon thickness compared with saline injection. The conclusions are limited to the 3 months after treatment owing to the large dropout rate. PMID- 27257168 TI - Accuracy of 2 Different Continuous Glucose Monitoring Systems in Patients Undergoing Cardiac Surgery. AB - BACKGROUND: Continuous glucose monitoring (CGM) is today provided by various techniques. This study aims to compare two different CGM-systems: the FreeStyle Libre subcutaneous continuous glucose monitoring system (SC-CGM) and the Eirus intravascular microdialysis continuous glucose monitoring system (MD-CGM) in patients undergoing cardiac surgery. METHODS: A total of 26 patients were equipped with both the SC-CGM and the MD-CGM systems. The SC-CGM system was placed subcutaneously in the left upper-arm and the MD-CGM system was placed in the superior vena cava. Reference blood glucose values were obtained by analyzing arterial blood in a blood gas analyzer. Reference glucose values were then paired with glucose values from both CGM-systems and analyzed for accuracy. RESULTS: In all, 514 paired MD-CGM/arterial blood gas glucose values and 578 paired SC CGM/arterial blood gas glucose values were obtained. Mean difference (SD) for the MD-CGM system was 0.9 (15.1) mg/dl and for the SC-CGM system -43.4 (20) mg/dl. ISO criteria (ISO15197:2013) were not met by either CGM system. In the Clarke error grid, all paired samples were within the zones AB for the MD-CGM system, and 94% in zone A. For the SC-CGM system, 99.1% of the paired samples were within zones AB, and 18.9% in zone A. Both the MD-CGM and the SC-CGM systems were reliable and used without complications. CONCLUSIONS: These results indicate that the Eirus intravascular microdialysis system monitors glucose continuously with superior accuracy compared to the FreeStyle Libre subcutaneous glucose monitoring system, which repeatedly measured a glucose value that was lower than the reference method. PMID- 27257170 TI - Accuracy Evaluation of a Blood Glucose Monitoring System in Chinese Individuals. PMID- 27257169 TI - Continuous Glucose Monitoring: Impact on Hypoglycemia. AB - The necessity of strict glycemic control is unquestionable. However, hypoglycemia remains a major limiting factor in achieving satisfactory glucose control, and evidence is mounting to show that hypoglycemia is not benign. Over the past decade, evidence has consistently shown that real-time continuous glucose monitoring improves glycemic control in terms of lowering glycated hemoglobin levels. However, real-time continuous glucose monitoring has not met the expectations of the diabetes community with regard to hypoglycemia prevention. The earlier trials did not demonstrate any effect on either mild or severe hypoglycemia and the effect of real-time continuous glucose monitoring on nocturnal hypoglycemia was often not reported. However, trials specifically designed to reduce hypoglycemia in patients with a high hypoglycemia risk have demonstrated a reduction in hypoglycemia, suggesting that real-time continuous glucose monitoring can prevent hypoglycemia when it is specifically used for that purpose. Moreover, the newest generation of diabetes technology currently available commercially, namely sensor-augmented pump therapy with a (predictive) low glucose suspend feature, has provided more convincing evidence for hypoglycemia prevention. This article provides an overview of the hypoglycemia outcomes of randomized controlled trials that investigate the effect of real-time continuous glucose monitoring alone or sensor-augmented pump therapy with a (predictive) low glucose suspend feature. Furthermore, several possible explanations are provided why trials have not shown a reduction in severe hypoglycemia. In addition, existing evidence is presented of real-time continuous glucose monitoring in patients with impaired awareness of hypoglycemia who have the highest risk of severe hypoglycemia. PMID- 27257171 TI - Australasian Diabetes Data Network: Building a Collaborative Resource. AB - Australasia is a region with a high incidence of type 1 diabetes (T1D). There are approximately 140 000 individuals with T1D, and of these 10 000 are children. Although the region covers a huge geographical area, most children with T1D are managed by tertiary academic centers in the major capital cities. Local longitudinal data collection has been in place for several decades in most of these centers, however ongoing national data collection had not been attempted. In 2012, with funding from the Juvenile Diabetes Research Foundation (JDRF) Australian Type 1 Clinical Research Network, a national collaboration was formed to provide ongoing longitudinal collection of T1D patient characteristics and outcomes. The initial phase of this collaboration, known as the Australasian Diabetes Data Network or ADDN, was led by the Australasian Paediatric Endocrine Group (APEG) and thus included only children and adolescents. The next phase, commenced in 2016, will see adult sites added through collaboration with the Australian Diabetes Society (ADS). As most of the initial centers had longitudinal data collection in place the model employed was to establish the transfer and collation of data already collected into a central database. This required the definition of a common data dictionary, ethics and governance procedures and the employment of technology to enable efficient and accurate information transfer and accessibility. The ADDN project received widespread support from the diabetes research community with study investigators representing 20 pediatric centers across the region. The first phase focused on the 5 largest centers and at the end of 2015 these centers were uploading patient data to the ADDN database on a quarterly basis resulting in 5271 patients with 83 506 diabetes visits. PMID- 27257172 TI - Blood's 70th anniversary: musings of a Blood editor, 2003-2007. PMID- 27257173 TI - Goodman JW, Hodgson GS. Evidence for stem cells in the peripheral blood of mice. Blood. 1962;19(6):702-714. PMID- 27257174 TI - The histiocytoses: as easy as ABC (or LCMRH). PMID- 27257175 TI - Sweeteners for factor H. PMID- 27257176 TI - mTOR signaling: new networks for ALL. PMID- 27257177 TI - Mouse model of MYD88L265P-dependent DLBCL. PMID- 27257178 TI - Cytogenetics in CML: more important than you think. PMID- 27257179 TI - Fibrin fixes fibrosis. PMID- 27257180 TI - Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene. AB - Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)(-) FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)(-) FL (mean, 0.77 vs 9 copy number alterations per case; P <001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P =075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)(-) FL displayed a mutational profile similar to t(14;18)(+) FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)(-) FL in adults indicate that these are two different disorders. PMID- 27257181 TI - Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study. AB - Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This long-term follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effective, with a complete remission (CR) rate of 34%. Translocation t(11;14) as the most prevalent aberration (59%) led to an improved CR rate after high-dose therapy (41.2% vs 20.0%; P = .02), translating into a prolonged hematologic event-free survival (hemEFS; median, 46.1 vs 28.1 months; P = .05) and a trend for better overall survival (median, not reached vs 93.7 months; P = .07). In multivariate analysis, t(11;14) was confirmed as a favorable prognostic factor regarding hemEFS along with lower values for the difference between involved and uninvolved free light chains. Conversely, deletion 13q14, gain of 1q21, and hyperdiploidy had no significant prognostic impact. The high-risk cytogenetic aberrations t(4;14), t(14;16), and del(17p13) conferred an unfavorable prognosis, although statistical significance was reached only for univariate CR analysis in this small group of 9 patients. Thus, t(11;14) positivity in HDM-treated AL patients conferred superior CR rates and hemEFS. In view of the reduced response of t(11;14) to bortezomib, this highlights the impact of therapy on the prognostic role of cytogenetic aberrations. PMID- 27257183 TI - Statins could be new treatment option in women with oestrogen receptor positive breast cancer. PMID- 27257182 TI - Protective mitochondrial transfer from bone marrow stromal cells to acute myeloid leukemic cells during chemotherapy. AB - Here we demonstrate that in a niche-like coculture system, cells from both primary and cultured acute myeloid leukemia (AML) sources take up functional mitochondria from murine or human bone marrow stromal cells. Using different molecular and imaging approaches, we show that AML cells can increase their mitochondrial mass up to 14%. After coculture, recipient AML cells showed a 1.5 fold increase in mitochondrial adenosine triphosphate production and were less prone to mitochondrial depolarization after chemotherapy, displaying a higher survival. This unidirectional transfer enhanced by some chemotherapeutic agents required cell-cell contacts and proceeded through an endocytic pathway. Transfer was greater in AML blasts compared with normal cord blood CD34(+) cells. Finally, we demonstrate that mitochondrial transfer was observed in vivo in an NSG immunodeficient mouse xenograft model and also occurred in human leukemia initiating cells and progenitors. As mitochondrial transfer provides a clear survival advantage following chemotherapy and a higher leukemic long-term culture initiating cell potential, targeting mitochondrial transfer could represent a future therapeutic target for AML treatment. PMID- 27257184 TI - A New Partnership for the New Year / Una Nueva Union Colectiva Para el Ano Nuevo. PMID- 27257185 TI - Social Determinants of Health for HIV Among Hispanic Women. PMID- 27257186 TI - Access Barriers to Prenatal Care in Emerging Adult Latinas. AB - Despite efforts to improve access to prenatal care, emerging adult Latinas in the United States continue to enter care late in their pregnancies and/or underutilize these services. Since little is known about emerging adult Latinas and their prenatal care experiences, the purpose of this study was to identify actual and perceived prenatal care barriers in a sample of 54 emerging adult Latinas between 18 and 21 years of age. More than 95% of the sample experienced personal and institutional barriers when attempting to access prenatal care. Results from this study lend support for policy changes for time away from school or work to attend prenatal care and for group prenatal care. PMID- 27257187 TI - Health Risk and Protective Factors Among Hispanic Women Living in the U.S.-Mexico Border Region. AB - As the Hispanic population continues to flourish in areas such the U.S.-Mexico border region, more attention needs to be focused on health factors among Hispanics. The purpose of this study was (1) to determine what specific health protective and health risk factors exist among Mexican/Mexican American women residing along the U.S.-Mexico border and (2) to determine the relationship between the protective and risk factors among these women. A sample of Mexican/Mexican American women (N = 98) participated in a structured interview that collected data on familism, Hispanic stress, depression, violence, and sexual risk and demographic variables. Religious factors had the largest influence on the health risk behaviors of alcohol intoxication and drug intoxication (p < .05), while familism influenced only condom use (p = .002) and a lifetime history of intimate partner violence (p = .039). Health care access also influenced the health risks of alcohol intoxication (p = .013), drug intoxication (p = .012), and condom use (p = .019). The study's results provide implications for clinical care and directions for future research. PMID- 27257188 TI - Nivel de Actividad Fisica, Autoeficacia, Beneficios y Barreras Percibidas en Mujeres Mayores Mexicanas Independientes (Physical Activity Level, Exercise Self Efficacy, Benefits and Perceived Barriers of Independent Mexican Older Women). AB - This descriptive comparative study examined differences in personal characteristics, exercise self-efficacy, benefits and barriers of independent elderly women to perform physical activity (PA) according with the PA level. Two hundred three women older than 60 years of age, from a community located in Nuevo Leon, Mexico participated in the study. Data was collected using: a) A personal data questionnaire, b) Exercise Self-Efficacy Scale, c) Exercise Benefits/ Barriers Scale and d) Physical Activity Scale for the Elderly were completed. Age was similar in participants with low and acceptable PA level. Participants with lower levels of PA reported consuming more medications, fewer years of education and lower values of exercise self-efficacy, benefits and barriers. In this sample, exercise self-efficacy and benefits were positively associated with the PA level. PMID- 27257189 TI - Self-Empowerment of Immigrant Latina Survivors of Domestic Violence: A Promotora Model of Community Leadership. AB - This article presents the results of a self-empowerment leadership intervention program for Latina immigrant survivors of domestic violence in Atlanta, Georgia. It builds on the literature base of the Promotora model, a public health model using peer information sharing as a tool for health promotion. This study used an embedded mixed-methods design with quantitative and qualitative components to evaluate the impact of a peer community leadership program called Lideres Results of single-subject analyses show that the participants experienced change in three components of self-empowerment: intrapersonal, interactional, and behavioral. The qualitative findings revealed that they overcame fear and gained knowledge as well as a sense that they could promote change in their community. These findings add support to a growing literature base that demonstrates how peer model programs can not only positively influence the well-being of the communities they serve but also have transformative effects on peer leaders themselves. Study findings can also inform future efforts to empower survivors through promotora approaches specifically in the context of domestic violence prevention. PMID- 27257192 TI - Complete and Closed Genome Sequences of 10 Salmonella enterica subsp. enterica Serovar Anatum Isolates from Human and Bovine Sources. AB - Salmonella enterica is an important pathogen transmitted by numerous vectors. Genomic comparisons of Salmonella strains from disparate hosts have the potential to further our understanding of mechanisms underlying host specificities and virulence. Here, we present the closed genome and plasmid sequences of 10 Salmonella enterica subsp. enterica serovar Anatum isolates from bovine and human sources. PMID- 27257190 TI - Factores que Influencian la Adquisicion de Infecciones de Transmision Sexual y VIH en Mujeres Jovenes Chilenas que Participaron en la Intervencion Online I STIPI (Factors That Influence the Acquisition of Sexually Transmitted Infections and HIV in Chilean Young Women Who Participated in the Online Intervention I STIPI). AB - The aim of this descriptive cross-sectional study was to investigate the following factors associated with sexually transmitted infections and human immunodeficiency virus prevention: (a) knowledge, (b) attitudes, (c) self efficacy, (d) vulnerability, (e) risky behaviors, (f) preventive behaviors, and (g) internet use among 40 Chilean women between 18 and 24 years who participated in the pilot of an Internet based STI/HIV prevention intervention (I-STIPI). A structured questionnaire available in a secure website was used for data collection and it included questions related to STI and HIV prevention. The results of the study indicated that young women are at risk of acquiring STIs and HIV and have special needs for prevention. Familiarity and frequency of use of internet in this population can be used for STIs and HIV prevention. PMID- 27257193 TI - Draft Genome Sequence of Bacillus subtilis ALBA01, a Strain with Antagonistic Activity against the Soilborne Fungal Pathogen of Onion Setophoma terrestris. AB - Bacillus subtilis is a nonpathogenic bacterium that lives in soil and has long been used as biological control agent in agriculture. Here, we report the genome sequence of a B. subtilis strain isolated from rhizosphere of onion that shows strong biological activity against the soilborne fungal pathogen Setophoma terrestris. PMID- 27257194 TI - Draft Genome Sequences of Mycobacterium kansasii Strains 1010001454, 1010001458, 1010001468, 1010001493, 1010001495, and 1010001469, Isolated from Environmental Sources. AB - Mycobacterium kansasii belongs to the nontuberculous mycobacteria (NTM) and causes opportunistic infections with both pulmonary and extrapulmonary manifestations. Here, we report the draft genome sequences of six environmental M. kansasii strains, designated 1010001495 (type I), 1010001469 (type II), 1010001468 (type III), 1010001458 (type IV), 1010001454 (type V), and 1010001493 (type V), originally isolated in five different European countries. PMID- 27257195 TI - Complete Genome Sequence of Streptomyces ambofaciens DSM 40697, a Paradigm for Genome Plasticity Studies. AB - The sequence of Streptomyces ambofaciens DSM 40697 was completely determined. The genome consists of an 8.1-Mbp linear chromosome with terminal inverted repeats of 210 kb. Genomic islands were identified, one of which corresponds to a new putative integrative and conjugative element (ICE) called pSAM3. PMID- 27257196 TI - Draft Genome Sequence of Oral Bacterium Streptococcus mutans JH1140. AB - Streptococcus mutans JH1140 is an oral bacterium known to produce the bacteriocin mutacin 1140, and the strain has been genetically engineered to combat dental caries. Here, we report the 2.0-Mb draft genome of S. mutans JH1140. This genome provides new insights into the strain's superior colonization properties and its utility in replacement therapy. PMID- 27257197 TI - Draft Genome Sequence of Bacillus sp. GZT, a 2,4,6-Tribromophenol-Degrading Strain Isolated from the River Sludge of an Electronic Waste-Dismantling Region. AB - Here, we report the draft genome sequence of Bacillus sp. strain GZT, a 2,4,6 tribromophenol (TBP)-degrading bacterium previously isolated from an electronic waste-dismantling region. The draft genome sequence is 5.18 Mb and has a G+C content of 35.1%. This is the first genome report of a brominated flame retardant degrading strain. PMID- 27257198 TI - Complete Genome Sequence of the Endophytic Fungus Diaporthe (Phomopsis) ampelina. AB - Diaporthe ampelina was isolated as an endophytic fungus from the root of Commiphora wightii, a medicinal plant collected from Dhanvantri Vana, Bangalore University, Bangalore, India. The whole genome is 59 Mb, contains a total of 905 scaffolds, and has a G+C content of 51.74%. The genome sequence of D. ampelina shows a complete absence of lovastatin (an anticholesterol drug) gene cluster. PMID- 27257199 TI - Draft Genome Sequence of Lactobacillus plantarum BFE 5092 Isolated from Maasai Fermented Milk. AB - The draft genome of Lactobacillus plantarum BFE 5092 isolated from the Maasai traditional fermented milk product kule naoto was sequenced, and sequence analysis showed the assembled genome size to be 3,285,094 bp, containing a predicted total of 3,111 protein-encoding genes, 17 rRNAs, and 70 tRNAs. PMID- 27257200 TI - Draft Genome Sequences of Listeria monocytogenes Serotype 4b Strains 944 and 2993 and Serotype 1/2c Strains 198 and 2932. AB - Listeria monocytogenes is a foodborne pathogen and the causative agent of listeriosis among humans and animals. The draft genome sequences of L. monocytogenes serotype 4b strains 944 and 2993 and serotype 1/2c strains 198 and 2932 are reported here. PMID- 27257201 TI - Complete Genome Sequence of Enterobacter cloacae B2-DHA, a Chromium-Resistant Bacterium. AB - Previously, we reported a chromium-resistant bacterium, Enterobacter cloacae B2 DHA, isolated from the landfills of tannery industries in Bangladesh. Here, we investigated its genetic composition using massively parallel sequencing and comparative analysis with other known Enterobacter genomes. Assembly of the sequencing reads revealed a genome of ~4.21 Mb in size. PMID- 27257202 TI - Draft Whole-Genome Sequences of 11 Bacillus cereus Food Isolates. AB - Bacillus cereus is a foodborne pathogen causing emetic and diarrheal-type syndromes. Here, we report the whole-genome sequences of 11 B. cereus food isolates. PMID- 27257204 TI - Draft Whole-Genome Sequence of Sphingobium sp. 22B, a Polycyclic Aromatic Hydrocarbon-Degrading Bacterium from Semiarid Patagonia, Argentina. AB - Sphingobium sp. 22B is a polycyclic aromatic hydrocarbon-degrading strain isolated from Patagonia, Argentina, with capabilities to withstand the environmental factors of that semiarid region. The draft genome shows the presence of genes related with responses to carbon starvation and drying environmental conditions. PMID- 27257203 TI - Draft Genome Sequence of a Mycobacterium africanum Clinical Isolate from Antioquia, Colombia. AB - Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex. Most commonly found in West African countries, it has scarcely been described in South America. Here, we report the first genome sequence of a Colombian M. africanum clinical isolate. It is composed of 4,493,502 bp, with 4,069 genes. PMID- 27257205 TI - Draft Genome Sequence of Bacillus cereus 905, a Plant Growth-Promoting Rhizobacterium of Wheat. AB - Bacillus cereus 905 is a plant growth-promoting rhizobacterium, isolated from wheat rhizosphere. The draft genome sequence of this strain is 5.39 Mb and harbors 5,412 coding sequences. PMID- 27257206 TI - Draft Genome Sequence of Arthrobacter enclensis NCIM 5488T for Secondary Metabolism. AB - Here, we report the draft genome sequence of Arthrobacter enclensis NCIM 5488(T), an actinobacterium isolated from a marine sediment sample from Chorao Island, Goa, India. This draft genome sequence consists of 4,226,231 bp with a G+C content of 67.08%, 3,888 protein-coding genes, 50 tRNAs, and 10 rRNAs. Analysis of the genome using bioinformatics tools such as antiSMASH and NaPDoS showed the presence of many unique natural product biosynthetic gene clusters. PMID- 27257207 TI - First Draft Genome Sequence of Staphylococcus condimenti F-2T. AB - This report describes the draft genome sequence of S. condimenti strain F-2(T) (DSM 11674), a potential starter culture. The genome assembly comprised 2,616,174 bp with 34.6% GC content. To the best of our knowledge, this is the first documentation that reports the whole-genome sequence of S. condimenti. PMID- 27257208 TI - Complete Genome Sequences of the Potyvirus Sweet potato virus 2 from East Timor and Australia. AB - We present here the first complete genome sequences of Sweet potato virus 2 (SPV2) from sweet potato in Australia and East Timor, and compare these with five complete SPV2 genome sequences from South Korea and one each from Spain and the United States. Both were closely related to SPV2 genomes from South Korea, Spain, and the United States. PMID- 27257209 TI - Correction for Sotnikova et al., Complete Genome Sequence of Mycobacterium bovis Strain BCG-1 (Russia). PMID- 27257210 TI - Complete Genome Sequences of Lytic Bacteriophages of Xanthomonas arboricola pv. juglandis. AB - Three bacteriophages, f20-Xaj, f29-Xaj, and f30-Xaj, with lytic activity against Xanthomonas arboricola pv. juglandis were isolated from walnut trees (VIII Bio Bio Region, Chile). These lytic bacteriophages have double-stranded DNA (dsDNA) genomes of 43,851 bp, 41,865 bp, and 44,262 bp, respectively. These are the first described bacteriophages with lytic activity against X. arboricola pv. juglandis that can be utilized as biocontrol agents. PMID- 27257211 TI - Complete Genome Sequence of Thiostrepton-Producing Streptomyces laurentii ATCC 31255. AB - Streptomyces laurentii ATCC 31255 produces thiostrepton, a thiopeptide class antibiotic. Here, we report the complete genome sequence for this strain, which contains a total of 8,032,664 bp, 7,452 predicted coding sequences, and a G+C content of 72.3%. PMID- 27257212 TI - Draft Genome Sequence of Methylobacterium sp. Strain ARG-1 Isolated from the White-Rot Fungus Armillaria gallica. AB - Methylobacterium sp. strain ARG-1 was isolated from a cell culture of hyphal tips of the white-rot fungus Armillaria gallica We describe here the sequencing, assembly, and annotation of its genome, confirming the presence of genes involved in methylotrophy. This is the first genome announcement of a strain of Methylobacterium associated with A. gallica. PMID- 27257213 TI - Complete Genome Sequence of Geobacter anodireducens SD-1T, a Salt-Tolerant Exoelectrogenic Microbe in Bioelectrochemical Systems. AB - Strain SD-1 is the type strain of the species Geobacter anodireducens, which was originally isolated from a microbial fuel cell reactor in the United States. The characteristic of this bacterium is its high electrochemical activity. Here, we report the fully assembled genome and plasmid sequence of G. anodireducens SD 1(T). PMID- 27257214 TI - TAp73 is a central transcriptional regulator of airway multiciliogenesis. AB - Motile multiciliated cells (MCCs) have critical roles in respiratory health and disease and are essential for cleaning inhaled pollutants and pathogens from airways. Despite their significance for human disease, the transcriptional control that governs multiciliogenesis remains poorly understood. Here we identify TP73, a p53 homolog, as governing the program for airway multiciliogenesis. Mice with TP73 deficiency suffer from chronic respiratory tract infections due to profound defects in ciliogenesis and complete loss of mucociliary clearance. Organotypic airway cultures pinpoint TAp73 as necessary and sufficient for basal body docking, axonemal extension, and motility during the differentiation of MCC progenitors. Mechanistically, cross-species genomic analyses and complete ciliary rescue of knockout MCCs identify TAp73 as the conserved central transcriptional integrator of multiciliogenesis. TAp73 directly activates the key regulators FoxJ1, Rfx2, Rfx3, and miR34bc plus nearly 50 structural and functional ciliary genes, some of which are associated with human ciliopathies. Our results position TAp73 as a novel central regulator of MCC differentiation. PMID- 27257216 TI - The Severity of Acute Illness and Functional Trajectories in Hospitalized Older Medical Patients. AB - BACKGROUND: Acute diseases and hospitalization are associated with functional deterioration in older persons. Although most of the functional decline occurs before hospitalization in response to the acute diseases, the role played by comorbidity in the functional trajectories around hospitalization is unclear. METHODS: Observational prospective study of 696 elderly individuals hospitalized in two Italian general medicine wards. Functional status of the elderly patients at 2 weeks before hospitalization (baseline), at hospital admission, and at discharge was measured by the Barthel Index. Comorbidity was measured at admission by the Geriatric Index of Comorbidity (GIC), a tool mostly based on illness severity. The association of GIC with changes in functional status before hospitalization (between baseline and admission), during hospitalization (between admission and discharge), and in the overall period between baseline and discharge was assessed by logistic regression analyses. Hospitalization associated disability (HAD) was defined as a functional decline between baseline and discharge. RESULTS: Illness severity (GIC 3-4 vs 1-2: odds ratio [OR] 2.2, 95% CI [confidence interval] 1.5-3.3, p < .0001) and older age significantly predicted prehospital functional decline (between baseline and admission). Illness severity (OR 1.9, 95% CI 1.2-3, p = .004) and older age were also predictive of HAD, even after adjustment for each coded primary discharge diagnosis. After adjustment for the occurrence of prehospital functional decline, however, illness severity and older age were not predictive of HAD anymore. CONCLUSIONS: The severity of illnesses was strongly associated with adverse functional outcomes around hospitalization, but frailty, intended as functional vulnerability to the acute disease before hospitalization, was a stronger predictor of HAD than illness severity and age. PMID- 27257215 TI - Jmjd2/Kdm4 demethylases are required for expression of Il3ra and survival of acute myeloid leukemia cells. AB - Acute myeloid leukemias (AMLs) with a rearrangement of the mixed-linage leukemia (MLL) gene are aggressive hematopoietic malignancies. Here, we explored the feasibility of using the H3K9- and H3K36-specific demethylases Jmjd2/Kdm4 as putative drug targets in MLL-AF9 translocated leukemia. Using Jmjd2a, Jmjd2b, and Jmjd2c conditional triple-knockout mice, we show that Jmjd2/Kdm4 activities are required for MLL-AF9 translocated AML in vivo and in vitro. We demonstrate that expression of the interleukin 3 receptor alpha (Il3ra also known as Cd123) subunit is dependent on Jmjd2/Kdm4 through a mechanism involving removal of H3K9me3 from the promoter of the Il3ra gene. Importantly, ectopic expression of Il3ra in Jmjd2/Kdm4 knockout cells alleviates the requirement of Jmjd2/Kdm4 for the survival of AML cells, showing that Il3ra is a critical downstream target of Jmjd2/Kdm4 in leukemia. These results suggest that the JMJD2/KDM4 proteins are promising drug targets for the treatment of AML. PMID- 27257217 TI - Validation of Consumer-Based Hip and Wrist Activity Monitors in Older Adults With Varied Ambulatory Abilities. AB - BACKGROUND: The accuracy of step detection in consumer-based wearable activity monitors in older adults with varied ambulatory abilities is not known. METHODS: We assessed the validity of two hip-worn (Fitbit One and Omron HJ-112) and two wrist-worn (Fitbit Flex and Jawbone UP) activity monitors in 99 older adults of varying ambulatory abilities and also included the validity results from the ankle-worn StepWatch as a comparison device. Nonimpaired, impaired (Short Physical Performance Battery Score < 9), cane-using, or walker-using older adults (62 and older) ambulated at a self-selected pace for 100 m wearing all activity monitors simultaneously. The criterion measure was directly observed steps. Intraclass correlation coefficients (ICC), mean percent error and mean absolute percent error, equivalency, and Bland-Altman plots were used to assess accuracy. RESULTS: Nonimpaired adults steps were underestimated by 4.4% for StepWatch (ICC = 0.87), 2.6% for Fitbit One (ICC = 0.80), 4.5% for Omron HJ-112 (ICC = 0.72), 26.9% for Fitbit Flex (ICC = 0.15), and 2.9% for Jawbone UP (ICC = 0.55). Impaired adults steps were underestimated by 3.5% for StepWatch (ICC = 0.91), 1.7% for Fitbit One (ICC = 0.96), 3.2% for Omron HJ-112 (ICC = 0.89), 16.3% for Fitbit Flex (ICC = 0.25), and 8.4% for Jawbone UP (ICC = 0.50). Cane-user and walker-user steps were underestimated by StepWatch by 1.8% (ICC = 0.98) and 1.3% (ICC = 0.99), respectively, where all other monitors underestimated steps by >11.5% (ICCs < 0.05). CONCLUSIONS: StepWatch, Omron HJ-112, Fitbit One, and Jawbone UP appeared accurate at measuring steps in older adults with nonimpaired and impaired ambulation during a self-paced walking test. StepWatch also appeared accurate at measuring steps in cane-users. PMID- 27257218 TI - The Benefit and Necessity of Collaborative Partnerships for Improved Health Care Systems / El Beneficio y la Necesidad de Colaborar Conjuntamente para Mejorar los Sistemas de Atencion de Salud. PMID- 27257220 TI - Cutting Corners: Provider Perceptions of Interpretation Services and Factors Related to Use of an Ad Hoc Interpreter. AB - INTRODUCTION: This study assessed health providers' perceptions of factors related to professional interpretation services and the association between these factors and the potential use of ad hoc interpreters. METHOD: Data were collected from a convenience sample of 150 health services providers at a large, regional health system in South Carolina. RESULTS: Providers rated "ability to communicate effectively during a clinical encounter" as paramount regarding the use of interpretation services. The most important factors related to the likely use of ad hoc interpreters (cutting corners) included locating a qualified interpreter, having to wait for a qualified interpreter, and technical difficulties regarding phone and video technology. CONCLUSION: Health care organizations may benefit from increasing staff awareness about patient safety and legal and regulatory risks involved with the use of ad hoc interpreters. PMID- 27257219 TI - Spanish-Speaking Limited English Proficiency Patients and Call Light Use. AB - INTRODUCTION: Despite a continuous increase of the limited English proficiency (LEP) population in the United States, disparities in the quality of care received in health care systems persist. METHOD: This qualitative study explores the perceptions of hospitalized LEP patients on their call light use, as well as their perceptions of a prototype of a new multilingual call light system, EloquenceTM. Individual interviews were conducted with 10 Spanish-speaking patient participants. RESULTS: Using a constant comparative method, the following themes emerged: (1) reasons for call light use, (2) challenges with communication, (3) patients' adaptation to language barriers, (4) perceived staff responses to call light, and (5) responses to the EloquenceTM demonstration. CONCLUSION: Data from this study shed light on the patient care experience of LEP patients and can help guide clinicians and administrators in providing culturally and linguistically competent care. PMID- 27257221 TI - Ethnoracial Variation in Depression Symptoms. AB - INTRODUCTION: While there is a long-standing tradition of research on the predictors of depression among women exposed to violence, little of this research has been conducted across ethnic and racial groups. METHOD: A cross-sectional study comparing a total of 191 women with a history of intimate partner violence were recruited from commercial, medical, and educational settings and by contact with agencies serving the needs of abused women, for example, shelters, community outreach. The study examined intimate partner violence and the adjustment of mothers of children ages 5 to 12 to explore both commonalities and differences in the ways in which four groups of women (African American, Biracial, Latina, and White women) cope with violence in their lives. In addition to demographic information, depression symptoms were assessed by self-report with the Center for Epidemiologic Studies Depression scale. RESULTS: The findings indicate that Latina women had significantly higher depression symptoms than did African American and White women. CONCLUSION: While it is important to assess the mental health needs of all abused women, these results show additional need for Latina women, those with low income and high violence exposure. PMID- 27257222 TI - Mujeres que Consumen Sustancias y su Vulnerabilidad frente al VIH en Santiago de Chile (Women Who Consume Substances and Their Vulnerability to HIV in Santiago of Chile). AB - INTRODUCTION: Women represent 15% of the people living with HIV in Chile. Risk behaviors for HIV are: multiple partners, unsafe sex, and exchange of sex for drugs/money. METHODOLOGY: A correlational design was used. A sample of 203 women who were sexually active and consumed substances within the last 3-months were selected for this study. RESULTS: The average age of the participants was 32.4 years (SD = 9.2) and 68.1% were housewives. The substance most commonly used was alcohol (95.1%) and marijuana (49.8%); 23.7% of the women were drunk or drugged before having sex; 74.4% had multiple sexual partners and 95.6% had unprotected sex. There is a significant correlation (p < 0.05) between substance abuse and HIV risk behaviors. CONCLUSION: It is necessary to develop more research to understand in depth the relationship between substance use and HIV risk among Chilean women. It is important to consider the use of substances to develop and implement HIV prevention programs in the Chilean community. PMID- 27257223 TI - Depression and Mobility Among Older Adults in Mexico: ENSANUT 2012. AB - INTRODUCTION: Depression among older people can be associated with limitations in physical mobility. METHOD: The ENSANUT 2012 data set was used. A secondary data analysis was conducted on a total sample of 6,525 Mexicans 60 years and older. RESULTS: Findings indicate that depressive symptoms among older people derive from their limitations in mobility rather than from their age. CONCLUSION: In Mexico, the prevalence of major depressive disorders is higher among older adults than among the rest of the adults. Hence, as the prevalence of this problem grows, the need for appropriate mental health attention will increase in Mexico. PMID- 27257224 TI - Guest Remarks From Celia Besore / Comentarios de Invitado de Celia Besore. PMID- 27257225 TI - Remarks From NAHN's President, Dan Suarez / Comentarios de Dan Suarez el Presidente de NAHN. PMID- 27257226 TI - Letter From the White House. PMID- 27257227 TI - Racial Differences in the Effects of Neighborhood Disadvantage on Residential Mobility in Later Life. AB - OBJECTIVES: Past research on the residential mobility of older adults has focused on individual-level factors and life course events. Less attention has been paid to the role of the residential environment in explaining residential mobility in older adults. We sought to understand whether neighborhood disadvantage had predictive utility in explaining residential relocation patterns, and whether associations differed between Whites and non-Whites. METHOD: Data are from the National Social Life, Health and Aging Project, a nationally representative sample of community-dwelling older adults. Neighborhoods were defined at the census tract level. Local movers (different census tract, same county) and distant movers (different county) were compared with stayers. RESULTS: After adjusting for individual-level factors, neighborhood disadvantage increased the likelihood of a local move, regardless of race/ethnicity. For non-Whites, higher neighborhood disadvantage decreased the likelihood of a distant move. Among local movers, Blacks and Latinos were less likely to improve neighborhood quality than Whites. DISCUSSION: Neighborhood disadvantage may promote local mobility by undermining person-environment fit. Racial differences in access to better neighborhoods persist in later life. Future research should explore how older adults optimize person-environment fit in the face of neighborhood disadvantage when the possibility of relocation to a better neighborhood may be restricted. PMID- 27257228 TI - Evaluative and Experienced Well-being of Caregivers of Parents and Caregivers of Children. AB - OBJECTIVES: Informal caregiving is an important source of support for aging parents and children. Yet the timing and nature of caring for parents versus children may result in different levels of well-being. Despite extensive studies on the well-being of caregivers of parents and of children, it remains elusive as to how evaluative and experienced well-being vary by caregiver type. METHOD: Using data from the 2012 and 2013 rounds of the American Time Use Survey, we examined how 216 caregivers of parents and 1,989 caregivers of children reported their evaluative well-being (life satisfaction) and experienced well-being (happiness, meaning, pain, sadness, stress, and tiredness). RESULTS: Caregivers of parents reported lower evaluative and experienced well-being than caregivers of children. The association between caregiver type and life satisfaction dissipated, whereas the associations of caregiver type with happiness, meaning, and sadness persisted after accounting for caregivers' demographic characteristics, socioeconomic resources, and time intensity. DISCUSSION: Experienced well-being appears to be more sensitive than evaluative well-being in detecting differences in well-being between these two types of caregivers. Given that the caregivers of parents do not receive the same level of institutional support as caregivers of children, social policies should aim to provide caregivers of parents with additional support. PMID- 27257230 TI - Taking up TOP. PMID- 27257229 TI - Theories of Memory and Aging: A Look at the Past and a Glimpse of the Future. AB - The present article reviews theories of memory and aging over the past 50 years. Particularly notable is a progression from early single-mechanism perspectives to complex multifactorial models proposed to account for commonly observed age deficits in memory function. The seminal mechanistic theories of processing speed, limited resources, and inhibitory deficits are discussed and viewed as especially important theories for understanding age-related memory decline. Additionally, advances in multivariate techniques including structural equation modeling provided new tools that led to the development of more complex multifactorial theories than existed earlier. The important role of neuroimaging is considered, along with the current prevalence of intervention studies. We close with predictions about new directions that future research on memory and aging will take. PMID- 27257232 TI - INFECTIOUS DISEASE. Mosquito hunters search for Zika vectors. PMID- 27257233 TI - EVOLUTION. Dogs may have been domesticated more than once. PMID- 27257235 TI - PLANETARY SCIENCE. Telescope and NASA mission get under Jupiter's skin. PMID- 27257234 TI - ARCHAEOLOGY. 'Culinary frontier' tracks Madagascar's Asian settlers. PMID- 27257236 TI - DEVELOPMENT. CRISPR views of embryos and cells. PMID- 27257237 TI - Peace of mind. PMID- 27257238 TI - Gatherings aim to bridge a wide divide. PMID- 27257239 TI - Stranding sleuth. PMID- 27257240 TI - ECOLOGY. Ecologically relevant data are policy-relevant data. PMID- 27257241 TI - IMMUNOLOGY. A lipid arsenal to control inflammation. PMID- 27257242 TI - ORIGIN OF LIFE. Beyond prebiotic chemistry. PMID- 27257243 TI - ASTRONOMY. Connecting the dots in magnetic reconnection. PMID- 27257244 TI - APPLIED OPTICS. Photonic multitasking enabled with geometric phase. PMID- 27257245 TI - DNA REPAIR. Drugging DNA repair. PMID- 27257246 TI - STATISTICS. Aligning statistical and scientific reasoning. PMID- 27257247 TI - Federal barriers to Cannabis research. PMID- 27257248 TI - No surprise that comb jellies poop. PMID- 27257249 TI - Digital identifiers for fungal species. PMID- 27257250 TI - Digital identifiers for fungal species--Response. PMID- 27257251 TI - Metalenses at visible wavelengths: Diffraction-limited focusing and subwavelength resolution imaging. AB - Subwavelength resolution imaging requires high numerical aperture (NA) lenses, which are bulky and expensive. Metasurfaces allow the miniaturization of conventional refractive optics into planar structures. We show that high-aspect ratio titanium dioxide metasurfaces can be fabricated and designed as metalenses with NA = 0.8. Diffraction-limited focusing is demonstrated at wavelengths of 405, 532, and 660 nm with corresponding efficiencies of 86, 73, and 66%. The metalenses can resolve nanoscale features separated by subwavelength distances and provide magnification as high as 170*, with image qualities comparable to a state-of-the-art commercial objective. Our results firmly establish that metalenses can have widespread applications in laser-based microscopy, imaging, and spectroscopy. PMID- 27257252 TI - Structure and torsional dynamics of the water octamer from THz laser spectroscopy near 215 MUm. AB - Clusters of eight water molecules play an important role in theoretical analysis of aqueous structure and dynamics but have proven to be challenging experimental targets. Here we report the high-resolution spectroscopic characterization of the water octamer. Terahertz (THz) vibration-rotation-tunneling (VRT) spectroscopy resolved 99 transitions with 1 part per million precision in a narrow range near 46.5 wave numbers, which were assigned to the h16 octamer via detailed isotope dilution experiments. Fitting to a semi-rigid symmetric top model supports predictions of two coexisting cuboidal structures and provides precise values for the changes in their rotational constants. Comparison with theory and previous spectroscopic data provides a characterization of the two structures and the observed torsional vibration and supports the prediction that the D2d symmetry structure is lower in energy than the S4 isomer. PMID- 27257253 TI - Peering through Jupiter's clouds with radio spectral imaging. AB - Radio wavelengths can probe altitudes in Jupiter's atmosphere below its visible cloud layers. We used the Very Large Array to map this unexplored region down to ~8 bar, ~100 kilometers below the visible clouds. Our maps reveal a dynamically active planet at pressures less than 2 to 3 bar. A radio-hot belt exists, consisting of relatively transparent regions (a low ammonia concentration, NH3 being the dominant source of opacity) probing depths to over ~8 bar; these regions probably coincide with 5-micrometer hot spots. Just to the south we distinguish an equatorial wave, bringing up ammonia gas from Jupiter's deep atmosphere. This wave has been theorized to produce the 5-micrometer hot spots; we observed the predicted radio counterpart of such hot spots. PMID- 27257254 TI - Orbital-exchange and fractional quantum number excitations in an f-electron metal, Yb2Pt2Pb. AB - Exotic quantum states and fractionalized magnetic excitations, such as spinons in one-dimensional chains, are generally expected to occur in 3d transition metal systems with spin 1/2. Our neutron-scattering experiments on the 4f-electron metal Yb2Pt2Pb overturn this conventional wisdom. We observe broad magnetic continuum dispersing in only one direction, which indicates that the underlying elementary excitations are spinons carrying fractional spin-1/2. These spinons are the emergent quantum dynamics of the anisotropic, orbital-dominated Yb moments. Owing to their unusual origin, only longitudinal spin fluctuations are measurable, whereas the transverse excitations such as spin waves are virtually invisible to magnetic neutron scattering. The proliferation of these orbital spinons strips the electrons of their orbital identity, resulting in charge orbital separation. PMID- 27257255 TI - Water splitting-biosynthetic system with CO2 reduction efficiencies exceeding photosynthesis. AB - Artificial photosynthetic systems can store solar energy and chemically reduce CO2 We developed a hybrid water splitting-biosynthetic system based on a biocompatible Earth-abundant inorganic catalyst system to split water into molecular hydrogen and oxygen (H2 and O2) at low driving voltages. When grown in contact with these catalysts, Ralstonia eutropha consumed the produced H2 to synthesize biomass and fuels or chemical products from low CO2 concentration in the presence of O2 This scalable system has a CO2 reduction energy efficiency of ~50% when producing bacterial biomass and liquid fusel alcohols, scrubbing 180 grams of CO2 per kilowatt-hour of electricity. Coupling this hybrid device to existing photovoltaic systems would yield a CO2 reduction energy efficiency of ~10%, exceeding that of natural photosynthetic systems. PMID- 27257256 TI - Environmentally relevant concentrations of microplastic particles influence larval fish ecology. AB - The widespread occurrence and accumulation of plastic waste in the environment have become a growing global concern over the past decade. Although some marine organisms have been shown to ingest plastic, few studies have investigated the ecological effects of plastic waste on animals. Here we show that exposure to environmentally relevant concentrations of microplastic polystyrene particles (90 micrometers) inhibits hatching, decreases growth rates, and alters feeding preferences and innate behaviors of European perch (Perca fluviatilis) larvae. Furthermore, individuals exposed to microplastics do not respond to olfactory threat cues, which greatly increases predator-induced mortality rates. Our results demonstrate that microplastic particles operate both chemically and physically on larval fish performance and development. PMID- 27257258 TI - TT-seq maps the human transient transcriptome. AB - Pervasive transcription of the genome produces both stable and transient RNAs. We developed transient transcriptome sequencing (TT-seq), a protocol that uniformly maps the entire range of RNA-producing units and estimates rates of RNA synthesis and degradation. Application of TT-seq to human K562 cells recovers stable messenger RNAs and long intergenic noncoding RNAs and additionally maps transient enhancer, antisense, and promoter-associated RNAs. TT-seq analysis shows that enhancer RNAs are short-lived and lack U1 motifs and secondary structure. TT-seq also maps transient RNA downstream of polyadenylation sites and uncovers sites of transcription termination; we found, on average, four transcription termination sites, distributed in a window with a median width of ~3300 base pairs. Termination sites coincide with a DNA motif associated with pausing of RNA polymerase before its release from the genome. PMID- 27257257 TI - ADP-ribose-derived nuclear ATP synthesis by NUDIX5 is required for chromatin remodeling. AB - Key nuclear processes in eukaryotes, including DNA replication, repair, and gene regulation, require extensive chromatin remodeling catalyzed by energy-consuming enzymes. It remains unclear how the ATP demands of such processes are met in response to rapid stimuli. We analyzed this question in the context of the massive gene regulation changes induced by progestins in breast cancer cells and found that ATP is generated in the cell nucleus via the hydrolysis of poly(ADP ribose) to ADP-ribose. In the presence of pyrophosphate, ADP-ribose is used by the pyrophosphatase NUDIX5 to generate nuclear ATP. The nuclear source of ATP is essential for hormone-induced chromatin remodeling, transcriptional regulation, and cell proliferation. PMID- 27257259 TI - Genomic and archaeological evidence suggest a dual origin of domestic dogs. AB - The geographic and temporal origins of dogs remain controversial. We generated genetic sequences from 59 ancient dogs and a complete (28x) genome of a late Neolithic dog (dated to ~4800 calendar years before the present) from Ireland. Our analyses revealed a deep split separating modern East Asian and Western Eurasian dogs. Surprisingly, the date of this divergence (~14,000 to 6400 years ago) occurs commensurate with, or several millennia after, the first appearance of dogs in Europe and East Asia. Additional analyses of ancient and modern mitochondrial DNA revealed a sharp discontinuity in haplotype frequencies in Europe. Combined, these results suggest that dogs may have been domesticated independently in Eastern and Western Eurasia from distinct wolf populations. East Eurasian dogs were then possibly transported to Europe with people, where they partially replaced European Paleolithic dogs. PMID- 27257260 TI - Flying free before building my nest. PMID- 27257261 TI - Epigenetic balance of gene expression by Polycomb and COMPASS families. AB - Epigenetic regulation of gene expression in metazoans is central for establishing cellular diversity, and its deregulation can result in pathological conditions. Although transcription factors are essential for implementing gene expression programs, they do not function in isolation and require the recruitment of various chromatin-modifying and -remodeling machineries. A classic example of developmental chromatin regulation is the balanced activities of the Polycomb group (PcG) proteins within the PRC1 and PRC2 complexes, and the Trithorax group (TrxG) proteins within the COMPASS family, which are highly mutated in a large number of human diseases. In this review, we will discuss the latest findings regarding the properties of the PcG and COMPASS families and the insight they provide into the epigenetic control of transcription under physiological and pathological settings. PMID- 27257262 TI - Editor's Choice-Rule-in of acute myocardial infarction: Focus on troponin. PMID- 27257263 TI - Validation of the diagnostic utility of D-dimer measurement in patients with acute aortic syndrome. AB - OBJECTIVE: The objective of this study was to evaluate the validity of D-dimer measurements for the diagnosis of acute aortic syndrome in patients admitted to hospital with acute chest pain. METHODS: A retrospective observational study design was used. Consecutive patients ( n=887) admitted to a tertiary hospital with acute chest pain (acute aortic syndrome, 123; acute pulmonary embolism, 29; and other disease, 735) from the emergency department between January 2011 and April 2014 were assessed to validate the diagnostic value of D-dimer measurements. RESULTS: The D-dimer level was significantly increased in patients with acute aortic syndrome (median (interquartile range) 4.9 (2.0-17.4) ug/ml) compared with control patients (median (interquartile range) 0.6 (0.3-1.4) ug/ml; p<0.001). At a cut-off point of 0.5 MUg/ml, the sensitivity for acute aortic syndrome was 0.97 (95% confidence interval 0.92-0.99) and was similar to that for acute pulmonary embolism (0.97 (0.82-0.99)). The age-adjusted D-dimer cut-off point, defined as age * 0.01 MUg/ml in patients ?50 years, successfully reduced the number of false-positive diagnoses by 13%, while still retaining a high sensitivity (0.96 (0.91-0.99)). The five false-negative diagnoses of acute aortic syndrome included three patients with intramural haematoma, one patient with a penetrating aortic ulcer and one patient with an impending aortic rupture. A combination of probability assessment and the D-dimer approach reduced the number of false-negatives from five patients to two patients. CONCLUSIONS: This study demonstrated that the D-dimer test can distinguish acute aortic syndrome from other diseases presenting with acute chest pain with high sensitivity and modest specificity. Using the D-dimer approach presents limitations with some subtypes of acute aortic syndrome, such as intramural haematoma. PMID- 27257264 TI - Medical mistrust in the context of Ebola: Implications for intended care-seeking and quarantine policy support in the United States. AB - This investigation explores Ebola conspiracy beliefs, a form of medical mistrust, and their potential impact on health behavior. Results of an online survey in the United States in December 2014 demonstrated that 16 percent of 202 participants held conspiracy beliefs. Participants who were less knowledgeable about Ebola, more mistrustful of medical organizations, and more xenophobic more strongly endorsed conspiracy beliefs. Participants who more strongly endorsed conspiracy beliefs reported that they would be less likely to seek care for Ebola and were less supportive of quarantining people returning from West Africa. Results suggest that medical mistrust may influence health behaviors during infectious disease outbreaks. PMID- 27257265 TI - Impact of emergency department visit on disease self-management in adults with depression. AB - Unexpected health-endangering events that lead to an emergency department visit may be perceived as "wake-up calls" and induce significant changes in health related behavior ("health shock" effect). This study uses two waves of a survey of 826 adults with depression and finds that having an emergency department visit(s) increased medication adherence by 7.6 percentage points ( p < 0.05) relative to non-emergency department visitors but had no significant effect on counseling attendance (0.02% points, p = 0.380). Emergency department visits may provide an opportune teachable moment to initiate targeted interventions for positive behavioral change in adults with depression. PMID- 27257266 TI - Leventhal's common-sense model and asthma control: Do illness representations predict success of an asthma rehabilitation? AB - This study investigates whether illness representations predict changes in asthma control or vice versa. Illness perceptions and asthma control were assessed in N = 113 asthma patients at the begin/end of an inpatient rehabilitation. Bivariate cross-lagged panel analyses showed that the illness representation dimensions Personal control, Consequences, Coherence, and Emotional representation predicted the change in asthma control, but asthma control did not predict illness representations. In multiple regression analyses with covariates, Personal control still predicted the change in asthma control. Illness beliefs assessed at the beginning of an intervention might help to identify patients with lower probability of treatment success. PMID- 27257268 TI - Recalling communities of practice. PMID- 27257267 TI - Imprisoned by Empathy: Familial Incarceration and Psychological Distress among African American Men in the National Survey of American Life. AB - The stress process model predicts that current incarceration of a family member should damage the health status of the inmate's relatives. We address this prediction with data from the National Survey of American Life, focusing exclusively on African American men (n = 1,168). In survey-adjusted generalized linear models, we find that familial incarceration increases psychological distress, but its effect attenuates ostensibly after controlling for other chronic strains. Familial incarceration remains statistically insignificant with the introduction of mastery and family emotional support and their respective interactions with familial incarceration. However, a statistical interaction between familial incarceration and former incarceration reveals that levels of psychological distress are significantly higher among never-incarcerated respondents whose family members are incarcerated but significantly lower among formerly incarcerated respondents whose family members are incarcerated. We conclude that familial incarceration's influence on black men's mental health status may be more complex than extant theory predicts. PMID- 27257272 TI - Smoking patterns and chronic kidney disease in US Hispanics: Hispanic Community Health Study/Study of Latinos. AB - BACKGROUND: Intermittent smoking is prevalent among Hispanics, but little is known about whether this smoking pattern associates with increased chronic kidney disease (CKD) risk in this population. The objective of the present study is to identify patterns of exposure associated with CKD in US Hispanics. METHODS: We used cross-sectional data on 15 410 participants of the Hispanics Community Health Study/the Study of Latinos, a population-based study of individuals aged 18-74 years, recruited in 2008 to 2011 from four US field centers (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA). Smoking exposure was obtained through a questionnaire. CKD was defined by an estimated glomerular filtration rate of <60 mL/min/1.73 m(2) or a urine albumin-to-creatinine ratio of >=30 mg/g. RESULTS: Approximately 14% of individuals were daily and 7% were intermittent smokers, and 16% were past smokers. There was a significant interaction between smoking status and pack-years of exposure (P = 0.0003). In adjusted models, there was an increased odds of CKD among daily, intermittent and past smokers by pack-years compared with never smokers. The association of intermittent smokers was significant at 10 pack-years [odds ratio (OR) = 1.38, 95% confidence intervals (CI) 1.06, 1.81], whereas for daily smokers this association was observed at 40 pack-years (OR = 1.43, 95% CI 1.09, 1.89). CONCLUSIONS: Our findings of increased risk of CKD among Hispanics who are intermittent smokers support screening and smoking cessation interventions targeted to this population for the prevention of CKD. It also suggests novel mechanistic pathways for kidney toxicity that should be further explored in future studies. PMID- 27257273 TI - Symptomatic fracture risk in the renal replacement therapy population. AB - Background: Bone fractures are an important cause of morbidity and mortality in patients on renal replacement therapy (RRT). The aim of this multicentre observational study was to quantify the incidence of radiologically proven bone fracture by anatomical site in prevalent RRT groups and study its relationship to potential risk factors. Methods: We performed a retrospective analysis of electronic records of all 2096 adults prevalent on RRT in the West of Scotland on 7 July 2010 across all hospitals (except one where inception was 1 August 2011) to identify all subsequent radiologically proven fractures during a median 3-year follow-up. Results: There were 340 fractures, with an incidence of 62.8 per 1000 patient-years. The incidences were 37.6, 99.2 and 57.6 per 1000 patient-years in the transplant, haemodialysis (HD) and peritoneal dialysis (PD) groups, respectively (P < 0.05). In the multivariable model, age and HD (relative to transplant or PD) were independently associated with increased risk of fractures, while primary glomerular disease, increasing serum albumin and taking alfacalcidol or lanthanum were associated with decreased risk. In a multivariable model of only HD patients, age was independently associated with an increased risk of fractures, while glomerular disease, high serum albumin and being on alfacalcidol and lanthanum were associated with decreased risk. In a multivariable model in transplant patients, there were no significant independent predictors of fracture. Conclusions: The risk of symptomatic bone fracture is high in RRT patients and is ~2.5 times higher in HD than in renal transplant patients, with the increased risk being independent of baseline factors. Fracture risk increases with age and lower serum albumin and is reduced if the primary renal diagnosis is glomerular disease. The possible protective role of alfacalcidol and lanthanum in HD patients deserves further exploration. PMID- 27257274 TI - A scoping review of adult chronic kidney disease clinical pathways for primary care. AB - Background: Chronic kidney disease (CKD) affects ~10% of the adult population. The majority of patients with CKD are managed by primary care physicians, and despite the availability of effective treatment options, the use of evidence based interventions for CKD in this setting remains suboptimal. Clinical pathways have been identified as effective tools to guide primary care physicians in providing evidence-based care. We aimed to describe the availability, characteristics and credibility of clinical pathways for adult CKD using a scoping review methodology. Methods: We searched Medline, Embase, CINAHL and targeted Internet sites from inception to 31 October 2014 to identify studies and resources that identified adult CKD clinical pathways for primary care settings. Study selection and data extraction were independently performed by two reviewers. Results: From 487 citations, 41 items were eligible for review: 7 published articles and 34 grey literature resources published between 2001 and 2014. Of the 41 clinical pathways, 32, 24 and 22% were from the UK, USA and Canada, respectively. The majority (66%, n = 31) of clinical pathways were static in nature (did not have an online interactive feature). The majority (76%) of articles/resources reported using one or more clinical practice guidelines as a resource to guide the clinical pathway content. Few articles described a dissemination and evaluation plan for the clinical pathway, but most reported the targeted end-users. Conclusions: Our scoping review synthesized available literature on CKD clinical pathways in the primary care setting. We found that existing clinical pathways are diverse in their design, content and implementation. These results can be used by researchers developing or testing new or existing clinical pathways and by practitioners and health system stakeholders who aim to implement CKD clinical pathways in clinical practice. PMID- 27257275 TI - The acute kidney injury e-alert and clinical care bundles: the road to success is always under construction. PMID- 27257278 TI - Effect of renal artery revascularization upon cardiac structure and function in atherosclerotic renal artery stenosis: cardiac magnetic resonance sub-study of the ASTRAL trial. AB - Background: Cardiac abnormalities are frequent in patients with atherosclerotic renovascular disease (ARVD). The Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial studied the effect of percutaneous renal revascularization combined with medical therapy compared with medical therapy alone in 806 patients with ARVD. Methods: This was a pre-specified sub-study of ASTRAL (clinical trials registration, current controlled trials number: ISRCTN59586944), designed to consider the effect of percutaneous renal artery angioplasty and stenting on change in cardiac structure and function, measured using cardiac magnetic resonance (CMR) imaging. Fifty-one patients were recruited from six selected ASTRAL centres. Forty-four completed the study (medical therapy n = 21; revascularization n = 23). Full analysis of CMR was possible in 40 patients (18 medical therapy and 22 revascularization). CMR measurements of left and right ventricular end systolic (LV and RVESV) and diastolic volume (LV and RVEDV), ejection fraction (LVEF) and mass (LVM) were made shortly after recruitment and before revascularization in the interventional group, and again after 12 months. Reporting was performed by CMR analysts blinded to randomization arm. Results: Groups were well matched for mean age (70 versus 72 years), blood pressure (148/71 versus 143/74 mmHg), degree of renal artery stenosis (75 versus 75%) and comorbid conditions. In both randomized groups, improvements in cardiac structural parameters were seen at 12 months, but there were no significant differences between treatment groups. Median left ventricular changes between baseline and 12 months (medical versus revascularization) were LVEDV -1.9 versus 5.8 mL, P = 0.4; LVESV -2.1 versus 0.3 mL, P = 0.7; LVM -5.4 versus -6.3 g, P = 0.8; and LVEF -1.5 versus -0.8%, P = 0.7. Multivariate regression also found that randomized treatment assignment was not associated with degree of change in any of the CMR measurements. Conclusions: In this sub-study of the ASTRAL trial, renal revascularization did not offer additional benefit to cardiac structure or function in unselected patients with ARVD. PMID- 27257276 TI - Markers of kidney disease and risk of subclinical and clinical heart failure in African Americans: the Jackson Heart Study. AB - BACKGROUND: African Americans and patients with chronic kidney disease (CKD) are at high risk for clinical heart failure (HF). In this study, we aimed to determine the association of markers of kidney disease with subclinical HF (by echocardiogram) and risk of clinical HF among a large, well-characterized community-based cohort of African American patients. We also examined whether the association of markers of kidney disease with HF was attenuated with adjustment for echocardiographic measures. METHODS: We studied participants in the Jackson Heart Study, a large community-based cohort of African Americans. Estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) were measured at baseline. We tested the association of eGFR and urine ACR with left ventricular mass (LVM), left ventricular ejection fraction (LVEF) and physician adjudicated incident HF. RESULTS: Among the 3332 participants in the study, 166 (5%) had eGFR <60 mL/min/1.73 m2 and 405 (12%) had urine ACR >=30 mg/g. In models adjusted for demographics, comorbidity and the alternative measure of kidney disease, lower eGFR and higher urine ACR were associated with higher LVM {beta coefficient 1.54 [95% confidence interval (CI) 0.78-2.31] per 10 mL/min/1.73 m2 decrease in eGFR and 2.87 (95% CI 1.85-3.88) per doubling of urine ACR}. There was no association of eGFR and urine ACR with LVEF [beta-coefficient -0.12 (95% CI -0.28-0.04) and -0.11 (95% CI -0.35-0.12), respectively]. There was no association of eGFR with the risk of incident HF [HR 1.02 (95% CI 0.91-1.14) per 10 mL/min/1.73 m2 decrease], while there was a significant association of urine ACR [HR 2.22 (95% CI 1.29-3.84) per doubling of urine ACR]. This association was only modestly attenuated with adjustment for LVM [HR 1.95 (95% CI 1.09-3.49)]. CONCLUSIONS: Among a community-based cohort of African Americans, lower eGFR and higher ACR were associated with higher LVM. Furthermore, higher urine ACR was associated with incident HF, which was not entirely explained by the presence of left ventricular disease. PMID- 27257279 TI - Multimodal imaging patterns predict survival in recurrent glioblastoma patients treated with bevacizumab. AB - BACKGROUND: Bevacizumab is a humanized antibody against vascular endothelial growth factor approved for treatment of recurrent glioblastoma. There is a need to discover imaging biomarkers that can aid in the selection of patients who will likely derive the most survival benefit from bevacizumab. METHODS: The aim of the study was to examine if pre- and posttherapy multimodal MRI features could predict progression-free survival and overall survival (OS) for patients with recurrent glioblastoma treated with bevacizumab. The patient population included 84 patients in a training cohort and 42 patients in a testing cohort, separated based on pretherapy imaging date. Tumor volumes of interest were segmented from contrast-enhanced T1-weighted and fluid attenuated inversion recovery images and were used to derive volumetric, shape, texture, parametric, and histogram features. A total of 2293 pretherapy and 9811 posttherapy features were used to generate the model. RESULTS: Using standard radiographic assessment criteria, the hazard ratio for predicting OS was 3.38 (P < .001). The hazard ratios for pre- and posttherapy features predicting OS were 5.10 (P < .001) and 3.64 (P < .005) for the training and testing cohorts, respectively. CONCLUSION: With the use of machine learning techniques to analyze imaging features derived from pre- and posttherapy multimodal MRI, we were able to develop a predictive model for patient OS that could potentially assist clinical decision making. PMID- 27257280 TI - PIK3CA mutations in meningioma. PMID- 27257284 TI - Health Care Practitioners' Perspectives on Deprescribing Anticholinergic and Sedative Medications in Older Adults. AB - BACKGROUND: Anticholinergic and sedative (ACh-Sed) medications are commonly prescribed for older adults and are associated with adverse events. OBJECTIVES: (1) To investigate perspectives of health care practitioners (HCPs) surrounding deprescribing (withdrawal) of ACh-Sed medications in older adults; (2) to assess HCPs' perspectives on the design and implementation of a report on a patient's exposure to ACh-Sed medications using the Drug Burden Index (DBI) pharmacological tool. METHODS: This was a qualitative study using focus groups with purposive samples of accredited pharmacists (APs), general practitioners (GPs), and specialist physicians (SPs). Participants were also asked to comment on a sample DBI report of a hypothetical patient and its potential role in practice. The discussions were audiorecorded, transcribed verbatim, and thematically analyzed to derive conceptual domains. QSR NVivo Version 10 was used for data management. RESULTS: Several barriers and enablers to deprescribing ACh-Sed medications in older adults were identified. The most noteworthy barrier to deprescribing related to devolving responsibility. Predominantly, APs expressed frustration surrounding disregard by GPs of their recommendations to deprescribe medications. GPs expressed that deprescribing should be conducted by SPs and vice versa. The DBI report supported and addressed some of the identified barriers to deprescribing ACh-Sed medications in older adults. The HCPs also identified several opportunities and considerations for implementing the DBI report in practice, mainly highlighting that ACh-Sed medications are not the only high-risk medications for older people. CONCLUSIONS: Although HCPs recognize the harms associated with ACh-Sed medication use, they devolve prescribing and management responsibility to other groups of HCPs. PMID- 27257283 TI - Consumption of whole grains and cereal fiber in relation to cancer risk: a systematic review of longitudinal studies. AB - CONTEXT: Evidence from previous reviews is supportive of the hypothesis that whole grains may protect against various cancers. However, the reviews did not report risk estimates for both whole grains and cereal fiber and only case control studies were evaluated. It is unclear whether longitudinal studies support this conclusion. OBJECTIVE: To evaluate associations between whole grains and cereal fiber in relation to risk of lifestyle-related cancers data from longitudinal studies was evaluated. DATA SOURCES: The following 3 databases were systematically searched: PubMed, EMBASE, and Cochrane CENTRAL. STUDY SELECTION: A total of 43 longitudinal studies conducted in Europe and North America that reported multivariable-adjusted risk estimates for whole grains (n = 14), cereal fiber (n = 23), or both (n = 6) in relation to lifestyle-related cancers were included. DATA EXTRACTION: Information on study location, cohort name, follow-up duration, sample characteristics, dietary assessment method, risk estimates, and confounders was extracted. DATA SYNTHESIS: Of 20 studies examining whole grains and cancer, 6 studies reported a statistically significant 6%-47% reduction in risk, but 14 studies showed no association. Of 29 studies examining cereal fiber intake in relation to cancer, 8 showed a statistically significant 6%-49% reduction in risk, whereas 21 studies reported no association. CONCLUSIONS: This systematic review concludes that most studies were suggestive of a null association. Whole grains and cereal fiber may protect against gastrointestinal cancers, but these findings require confirmation in additional studies. PMID- 27257285 TI - Saving the Elderly From Drug-Related Harm. PMID- 27257287 TI - Muscle Trigger Points and Pressure Pain Sensitivity Maps of the Feet in Women with Fibromyalgia Syndrome. AB - OBJECTIVE : To investigate the presence of trigger points (TrPs) in feet musculature and topographical pressure sensitivity maps of the feet as well as the relationship between TrPs, pressure pain maps, and clinical variables in women with fibromyalgia (FMS). METHODS : Fifty-one FMS women and 24 comparable healthy women participated. TrPs within the flexor hallucis brevis, adductor hallucis, dorsal interossei, extensor digitorum brevis, and quadratus plantae, as well as external and internal gastrocnemius, were explored. Pressure pain thresholds (PPTs) were assessed in a blind manner over seven locations on each foot. Topographical pressure sensitivity maps of the plantar region were generated using the averaged PPT of each location. RESULTS : The prevalence rate of foot pain was 63% (n = 32). The number of active TrPs for each FMS woman with foot pain was 5 +/- 1.5 without any latent TrPs. Women with FMS without foot pain and healthy controls had only latent TrPs (2.2 +/- 0.8 and 1.5 +/- 1.3, respectively). Active TrPs in the flexor hallucis brevis and adductor hallucis muscles were the most prevalent. Topographical pressure pain sensitivity maps revealed that FMS women with foot pain had lower PPT than FMS women without pain and healthy controls, and higher PPT on the calcaneus bone (P < 0.001). CONCLUSIONS : The presence of foot pain in women with FMS is high. The referred pain elicited by active TrPs in the foot muscles reproduced the symptoms in these patients. FMS women suffering foot pain showed higher pressure hypersensitivity in the plantar region than those FMS women without pain. PMID- 27257288 TI - Pregabalin Improves Pain Scores in Patients with Fibromyalgia Irrespective of Comorbid Osteoarthritis. AB - OBJECTIVE: Fibromyalgia (FM) is a chronic pain disorder with patients frequently suffering from comorbid conditions, including osteoarthritis (OA). Data on how FM patients with comorbid OA respond to recommended therapies (such as pregabalin) could help their treatment. DESIGN: This was a pooled exploratory analysis of three randomized placebo-controlled clinical trials of pregabalin in FM patients to assess the impact of comorbid OA on the response to pregabalin. METHODS: Patients were divided into those with and without comorbid OA. Difference in change in least squares (LS) mean pain score at endpoint (assessed by 0-10 numeric rating scale, controlled for baseline pain score) with pregabalin (300 mg/day and 450 mg/day) vs placebo was assessed. Changes in Patient Global Impression of Change (PGIC) responders and Fibromyalgia Impact Questionnaire (FIQ) total score were also assessed. RESULTS: There were 1665 patients in the analysis set (558, placebo; 552, pregabalin 300 mg/day; 555, pregabalin 450 mg/day), including 296 with comorbid OA. Pregabalin 450 mg/day significantly improved the LS mean (95% confidence interval) difference in pain score vs placebo in patients with (0.99 [0.44, 1.55], P < 0.001), and without (0.64 [0.39, 0.89], P < 0.001) OA. Improvements with pregabalin 300 mg/day with (0.31 [-0.25, 0.86], P = 0.276) and without (0.51 [0.25, 0.76], P < 0.001) OA were not consistently significant. Improvements in PGIC and FIQ total score were observed in patients with and without comorbid OA. CONCLUSIONS: FM patients with or without comorbid OA respond to treatment with pregabalin 450mg/day with significant improvements in pain intensity scores. These data could provide guidance to healthcare professionals treating these patients. PMID- 27257290 TI - Lumbar Rib Causing Chronic Pain After Minor Thoracic Injury. PMID- 27257291 TI - A Small GTPase, OsRab6a, is Involved in the Regulation of Iron Homeostasis in Rice. AB - Plants have evolved two distinct strategies to acquire iron (Fe) from soils. However, the regulatory mechanisms underlying the Fe acquisition remain largely elusive. There is emerging evidence that small GTPases are involved in the responses of plants to environmental cues. Here, we identified a gene encoding a small GTPase, OsRab6a, in rice and characterized its role in Fe acquisition by generating transgenic rice plants with overexpression and knockdown of OsRab6a OsRab6a shared conserved functional domains with other known members of the Rab subfamily and localized ubiquitously in the cytoplasm and nucleus. The expression of OsRab6a was rapidly and transiently up-regulated by Fe deficiency. No differences in growth and development among the OsRab6a-overexpression, OsRab6a RNAi (RNA interference) and wild-type plants were detected when grown in Fe sufficient medium. However, overexpression of OsRab6a in rice plants conferred greater tolerance to Fe deficiency than RNAi and wild-type plants, as evidenced by higher seedling height, and greater biomass, Chl contents and Fe concentrations in shoots, roots and grains in the overexpression lines than wild type and RNAi plants. Moreover, the overexpression lines exhibited larger root systems than wild-type and RNAi plants in Fe-deficient medium. Exposure to Fe deficient medium led to up-regulation of OsIRO2, OsIRT1, OsNAS1 and OsNAS2 in both wild-type and transgenic rice plants, with the magnitude of up-regulation positively correlated with the expression levels of OsRab6a These results may suggest that OsRab6a plays an important role in the regulation of Fe acquisition in rice plants by modulating physiological processes involved in Fe acquisition and root system architecture in response to Fe-deficient medium. PMID- 27257292 TI - Lateral Cricoarytenoid Release: Development of a Novel Surgical Treatment Option for Adductor Spasmodic Dysphonia in a Canine Laryngeal Model. AB - OBJECTIVE: To investigate the efficacy of a novel adductor muscle-releasing technique designed to decrease the force of vocal fold adduction, as a potential surgical therapy for patients with adductor spasmodic dysphonia (ADSD). STUDY DESIGN: Experimental animal study. METHODS: A canine laryngeal model was used to assess the acute and sustained efficacy of a lateral cricoarytenoid (LCA) muscle release. A total of 34 canine hemilaryngeal preparations were divided among 7 experimental groups. The LCA muscle was separated from its cricoid cartilage origin via an open, anterior, submucosal approach. The laryngeal adductory pressures (LAP) were assessed pre- and post-muscle release via direct recurrent laryngeal nerve stimulation. Measurements were repeated at 1.5, 3, or 6 months postoperatively. Another study evaluated release of the thyroarytenoid (TA) muscle from its thyroid cartilage origin. RESULTS: Releasing the LCA muscle demonstrated a significant decrease in LAP acutely and was maintained at all 3 time points with the aid of a barrier (P < .05). Without the barrier, the LCA muscle reattached to the cricoid. Acute release of the TA muscle did not significantly decrease the LAP. CONCLUSIONS: The proposed LCA release procedure may provide patients with a permanent treatment option for ADSD. However, longer term studies and human trials are needed. PMID- 27257295 TI - Advert. PMID- 27257293 TI - Physical Activity of Malaysian Primary School Children: Comparison by Sociodemographic Variables and Activity Domains. AB - This study describes the physical activity of primary school children according to sociodemographic characteristics and activity domains. Using the Malaysian South East Asian Nutrition Surveys data, 1702 children aged 7 to 12 years were included in the analysis. Physical activity was reported as a total score and categorized into low, medium, and high levels based on Physical Activity Questionnaire for Older Children. Higher overall activity scores were found in boys, younger age, non-Chinese ethnicity, and normal body mass index category. Sex, age, and ethnicity differences were found in structured or organized, physical education, and outside-of-school domain scores. Transport-related scores differed by age group, ethnicity, household income, and residential areas but not among the three physical activity levels. Participation of girls, Chinese, and older children were low in overall and almost all activity domains. Sociodemographic characteristics are important factors to consider in increasing the different domains of physical activity among Malaysian children. PMID- 27257294 TI - Burdensomeness, Belongingness, and Capability: Assessing the Interpersonal Psychological Theory of Suicide With MMPI-2-RF Scales. AB - Given the emerging body of literature demonstrating the validity of the interpersonal-psychological theory of suicide (IPTS), and the importance of increasing our understanding of the development of risk factors associated with suicidal behavior, it seems worthwhile both to expand IPTS research via Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) correlates and to expand the availability of methods by which to assess the constructs of the IPTS. The present study attempted to do so in a large adult outpatient mental health sample by (a) inspecting associations between the IPTS constructs and the substantive scales of the MMPI-2-RF and (b) exploring the utility of MMPI-2-RF scale-based algorithms of the IPTS constructs. Correlates between the IPTS constructs and the MMPI-2-RF scales scores largely followed a pattern consistent with theory-based predictions, and we provide preliminary evidence that the IPTS constructs can be reasonably approximated using theoretically based MMPI-2-RF substantive scales. Implications of these findings are discussed. PMID- 27257296 TI - Advert. PMID- 27257297 TI - Advert. PMID- 27257298 TI - Society officers. PMID- 27257301 TI - Guest editorial. PMID- 27257302 TI - Chemical Imaging of Heterogeneous Muscle Foods Using Near-Infrared Hyperspectral Imaging in Transmission Mode. AB - Foods and biomaterials are, in general, heterogeneous and it is often a challenge to obtain spectral data which are representative for the chemical composition and distribution. This paper presents a setup for near-infrared (NIR) transmission imaging where the samples are completely trans-illuminated, probing the entire sample. The system measures falling samples at high speed and consists of an NIR imaging scanner covering the spectral range 760-1040 nm and a powerful line light source. The investigated samples were rather big: whole pork bellies of thickness up to 5 cm, salmon fillets with skin, and 3 cm thick model samples of ground pork meat. Partial least square regression models for fat were developed for ground pork and salmon fillet with high correlations (R = 0.98 and R = 0.95, respectively). The regression models were applied at pixel level in the hyperspectral transmission images and resulted in images of fat distribution where also deeply embedded fat clearly contributed to the result. The results suggest that it is possible to use transmission imaging for rapid, nondestructive, and representative sampling of very heterogeneous foods. The proposed system is suitable for industrial use. PMID- 27257303 TI - Changes in migraine before and after menopause in Japanese climacteric women. AB - Introduction We conducted a questionnaire survey of Japanese women with migraine who presented at neurology and gynecology headache clinics to assess how the frequency and severity of migraine in pre-, peri-, and postmenopausal women changed as compared with what they experienced in their 20s and 30s. Methods The study group comprised 171 women with migraine (mean age 48.5) at the time of the survey. They were requested to fill out a self-administered questionnaire. Results (1) The current frequency and severity of migraine were claimed to be higher than that in their 20s and 30s. (2) More than 50% of postmenopausal women responded that migraines were currently less frequent than in their 20s and 30s. (3) The largest proportion of postmenopausal women responded that migraine was currently less severe than during any other period. Conclusions Our survey demonstrated that there are trends toward fewer migraine attacks and milder symptoms in postmenopausal Japanese women. PMID- 27257304 TI - Case report of an alleviation of pain symptoms in hypnic headache via greater occipital nerve block. AB - Background Hypnic headache is a rare primary headache disorder with a few hundred described cases so far. Due to the fact that this headache disease is rare, there are no placebo-controlled oral medication studies. After all reported oral medication failed to control pain symptoms of a hypnic headache disease, we were able to reduce pain intensity and frequency via two greater occipital nerve (GON) blocks. Case We report on a 74-year-old patient diagnosed with hypnic headache in our headache outpatient department two years ago. Over a course of nine months none of the recommended oral drugs had an effect in pain alleviation and we decided to try an occipital nerve injection therapy. Two GON-blocks then led to a stable and significant pain reduction over the course of six months during monthly follow-ups. Conclusion GON block can be a successful therapeutic approach for the treatment of hypnic headache when oral medication fails. PMID- 27257305 TI - Party Identification, Contact, Contexts, and Public Attitudes toward Illegal Immigration. AB - Illegal immigration is a contentious issue on the American policy agenda. To understand the sources of public attitudes toward immigration, social scientists have focused attention on political factors such as party identification; they have also drawn on theories of intergroup contact to argue that contact with immigrants shapes immigration attitudes. Absent direct measures, contextual measures such as respondents' ethnic milieu or proximity to salient geographic features (such as borders) have been used as proxies of contact. Such a research strategy still leaves the question unanswered - is it contact or context that really matters? Further, which context, and for whom? This article evaluates the effects of party identification, personal contact with undocumented immigrants, and contextual measures (county Hispanic population and proximity to the US Mexico border) on American attitudes toward illegal immigration. It finds that contextual factors moderate the effects of political party identification on attitudes toward illegal immigration; personal contact has no effect. These findings challenge the assumption that contextual measures act as proxies for interpersonal contact. PMID- 27257306 TI - Bias in the Flesh: Skin Complexion and Stereotype Consistency in Political Campaigns. AB - There is strong evidence linking skin complexion to negative stereotypes and adverse real-world outcomes. We extend these findings to political ad campaigns, in which skin complexion can be easily manipulated in ways that are difficult to detect. Devising a method to measure how dark a candidate appears in an image, this paper examines how complexion varied with ad content during the 2008 presidential election campaign (study 1). Findings show that darker images were more frequent in negative ads-especially those linking Obama to crime-which aired more frequently as Election Day approached. We then conduct an experiment to document how these darker images can activate stereotypes, and show that a subtle darkness manipulation is sufficient to activate the most negative stereotypes about Blacks-even when the candidate is a famous counter-stereotypical exemplar Barack Obama (study 2). Further evidence of an evaluative penalty for darker skin comes from an observational study measuring affective responses to depictions of Obama with varying skin complexion, presented via the Affect Misattribution Procedure in the 2008 American National Election Study (study 3). This study demonstrates that darker images are used in a way that complements ad content, and shows that doing so can negatively affect how individuals evaluate candidates and think about politics. PMID- 27257307 TI - Adolescent Determinants of Abortion Attitudes: Evidence from the Children of the National Longitudinal Survey of Youth. AB - The stability of abortion opinions suggests that pre-adult factors influence these attitudes more than contemporaneous political events. Surprisingly, however, we know little about the origins of abortion opinions, no doubt because the majority of research focuses on cross-sectional analyses of patterns across cohorts. We use a developmental model that links familial and contextual factors during adolescence to abortion attitudes years later when respondents are between 21 and 38 years old. Findings show that religious adherence and maternal gender role values are significant predictors of adult abortion opinions, even after controlling for contemporaneous religious adherence and the respondents' own views on gender roles. Adolescent religious adherence matters more than religious denomination for adult abortion attitudes. The results have important implications for future trends in abortion attitudes in light of declining religiosity among Americans. PMID- 27257308 TI - Sticker Shock: How Information Affects Citizen Support for Public School Funding. AB - This study examines the role of information in shaping public opinion in the context of support for education spending. While there is broad public support for increasing government funding for public schools, Americans tend to underestimate what is currently spent. We embed a series of experiments in a nationally representative survey administered in 2012 (n = 2,993) to examine whether informing citizens about current levels of education spending alters public opinion about whether funding should increase. Providing information on per-pupil spending in a respondent's local school district reduces the probability that he or she will express support for increasing spending by 22 percentage points on average. Informing respondents about state-average teacher salaries similarly depresses support for salary increases. These effects are larger among respondents who underestimate per-pupil spending and teacher salaries by a greater amount, consistent with the idea that the observed changes in opinion are driven, at least in part, by informational effects, as opposed to priming alone. PMID- 27257309 TI - Support for Government Provision of Health Care and the Patient Protection and Affordable Care Act. AB - Since the 1930s, US politicians have argued about whether healthcare should be the responsibility of the federal government. Both major political parties have cited public opinion concerning Americans' support for or rejection of government provision of healthcare to support their position. With the passage of the Patient Protection and Affordable Care Act (ACA) in 2010, however, the political debate has changed. Where it had been about the government provision of healthcare as an abstract principle, it became a debate imbued with evaluations of the implementation of the ACA itself. This spawned a new line of research examining the consequences of the ACA's implementation on public attitudes toward government provision of healthcare. The change in support for government provision of healthcare and the new post-ACA research highlight a need for a long term examination of trends in support over the past two decades that will provide context for the new studies. This study provides that examination. PMID- 27257310 TI - Social Media Analyses for Social Measurement. AB - Demonstrations that analyses of social media content can align with measurement from sample surveys have raised the question of whether survey research can be supplemented or even replaced with less costly and burdensome data mining of already-existing or "found" social media content. But just how trustworthy such measurement can be-say, to replace official statistics-is unknown. Survey researchers and data scientists approach key questions from starting assumptions and analytic traditions that differ on, for example, the need for representative samples drawn from frames that fully cover the population. New conversations between these scholarly communities are needed to understand the potential points of alignment and non-alignment. Across these approaches, there are major differences in (a) how participants (survey respondents and social media posters) understand the activity they are engaged in; (b) the nature of the data produced by survey responses and social media posts, and the inferences that are legitimate given the data; and (c) practical and ethical considerations surrounding the use of the data. Estimates are likely to align to differing degrees depending on the research topic and the populations under consideration, the particular features of the surveys and social media sites involved, and the analytic techniques for extracting opinions and experiences from social media. Traditional population coverage may not be required for social media content to effectively predict social phenomena to the extent that social media content distills or summarizes broader conversations that are also measured by surveys. PMID- 27257315 TI - The Occurrence of Postconflict Skills in Captive Immature Chimpanzees (Pan troglodytes). AB - Conflict management strategies can reduce costs of aggressive competition in group-living animals. Postconflict behaviors such as reconciliation and third party postconflict affiliation are widely accepted as social skills in primates and have been demonstrated in many species. Although immature primates possess a repertoire of species-specific behaviors, it is thought that they gradually develop appropriate social skills throughout prolonged juvenility to establish and maintain complex social relationships within their group. We examined the occurrence of postconflict skills in five immature chimpanzees (Pan troglodytes) over 15 mo, focusing on interactions that were not with the subject's mother. We observed reconciliation, with conciliatory tendencies comparable to adults, and provide the first evidence that captive immature chimpanzees commonly reconciled using social play. However, immatures were not more likely to reconcile valuable than nonvaluable relationships. We also observed third party postconflict affiliation although at a lower level than reported for adults. Our results provide evidence for postconflict skills in immature chimpanzees but the lack of higher conciliatory tendency with valuable partners and low occurrence of third party affiliation indicates extended juvenility may be required refine these skills. Further work is needed to investigate whether these behaviors have the same function and effectiveness as those found in adults. PMID- 27257316 TI - Bridging Social Capital and Individual Earnings: Evidence for an Inverted U. AB - Based on data on a cross section of individuals surveyed in the 1999-2002 wave of World and European Values Surveys, we investigate the multilateral associations between bridging social capital, individuals' earnings, as well as social trust and employment status. Our analysis provides robust evidence that the relationship between bridging social capital and earnings is inverted-U shaped. We carry out a range of tests in order to ascertain that this result is not driven by regressor endogeneity or omitted variables bias. We also identify significant interaction effects between bridging social capital, social trust, and employment status. PMID- 27257318 TI - Scientific publications - Unscientific demeanor: Where are the problems? PMID- 27257319 TI - Disease registry in the Armed Forces Medical Services: An Idea Whose Time Has Come. PMID- 27257317 TI - Can glycoprofiling be helpful in detecting prostate cancer? AB - Glycans are chains of carbohydrates attached to proteins (glycoproteins and proteoglycans) or lipids (glycolipids). Glycosylation is a posttranslational modification and glycans have a wide range of functions in a human body including involvement in oncological diseases. Change in a glycan structure cannot only indicate presence of a pathological process, but more importantly in some cases also its stage. Thus, a glycan analysis has a potential to be an effective and reliable tool in cancer diagnostics. Lectins are proteins responsible for natural biorecognition of glycans, even carbohydrate moieties still attached to proteins or whole cells can be recognized by lectins, what makes them an ideal candidate for designing label-free biosensors for glycan analysis. In this review we would like to summarize evidence that glycoprofiling of biomarkers by lectin-based biosensors can be really helpful in detecting prostate cancer. PMID- 27257320 TI - Mutation in AIDS restriction gene affecting HIV infection and disease progression in a high risk group from Northeastern India. AB - BACKGROUND: HIV estimates for 2009 released by National AIDS Control Organization (NACO) reveals that 2.4 million people in India were living with HIV, 39% being female, 4.4% children and 82.4% adult males between the age group of 15 and 49 years. Persons with host genetic polymorphism CCR5Delta32 mutation are known to be partially or fully resistant to HIV infection. Persons with mutation affecting both the alleles (homozygous) are resistant to HIV infection whereas single allele (heterozygous) polymorphism leads to slower progression to AIDS. CCR5Delta32 mutation is commoner in Caucasians but less prevalent amongst Africans and Asians thereby rendering them susceptible to HIV infection. METHOD: 571 HIV serologically naive subjects from a young and homogenous male population hailing from the seven northeastern states; West Bengal and Gorkha people were selected. All the subjects belonged to a special high risk group, sexually active and typically working in difficult and uncongenial terrain involved in frequent moves including overseas missions. Their family lives are severely disrupted. 181 HIV seropositive cases of which 92 cases that were admitted in a large tertiary care hospital were also included. The distribution of CCR5Delta32 polymorphism amongst both HIV seronegative (HSN) and HIV seropositive study cohorts (HSP) using molecular methods was studied. RESULTS AND CONCLUSION: There was failure to detect any CCR5Delta32 amongst this study group suggesting that this population from the northeastern India, West Bengal and Gorkha people are not protected by this specific host polymorphism in respect of acquisition of HIV infection as well as progression to AIDS. PMID- 27257321 TI - Correlates of hematuria on glomerular histology and electron microscopy in IgA nephropathy. AB - BACKGROUND: Hematuria is the most important clinical manifestation of IgA nephropathy. This study was undertaken with the objective to describe the spectrum of histological changes with reference to the Oxford classification and the ultrastructural changes in the glomerular basement membrane and to correlate them with hematuria. METHODS: 66 patients who underwent renal biopsy for IgA nephropathy were evaluated histologically by the Oxford system and also subject to electron microscopic examination for glomerular immune deposits, as well as alterations in the glomerular basement membrane. RESULTS: On comparing the histological scores generated by the Oxford classification with degree of hematuria, it was found that the status of 'endocapillary proliferation' and the status of 'tubular atrophy and interstitial fibrosis showed a significant correlation. Correlation of hematuria with location of the deposits, i.e. mesangial only, and mesangial with capillary wall deposits (subendothelial and subepithelial) did not show any association. Other alterations of the GBM were seen in 12 cases. The changes included thinning alone in 4 cases, thinning and lamellar splitting in 5 cases, and lamellar splitting alone in 2 cases. CONCLUSION: At presentation, endocapillary proliferation is one histological parameter which shows close association with hematuria. PMID- 27257322 TI - A prospective interventional study of effect of accelerated orthokeratology on the corneal curvature and refraction among young adults with myopia. AB - BACKGROUND: Orthokeratology with reverse geometry contact lens is a non-surgical alternative to conventional contact lenses for correction of myopia. However, the strength of evidence for its efficacy and safety is limited to retrospective studies and only a few prospective studies. This prospective study, the first on Indian subjects, evaluated the outcome of orthokeratology among young myopes. METHODS: Fifty eyes of 25 young myopes (age 19-29 years) with myopia of -1 to 5.0 diopter underwent accelerated orthokeratology using the reverse geometry ortho K LK lenses for correction of myopia. They were followed up prospectively with weekly vision, refraction, corneal topography, and pachymetry to assess the correction of myopia. RESULTS: The mean Log MAR vision corrected from 0.748 +/- 0.225 at base line to 0.025 +/- 0.0630 at 12 weeks with 86% achieving 6/6 unaided day time vision. This was associated with significant central corneal flattening and thinning. The lenses were well tolerated with no significant complications. CONCLUSION: Overnight accelerated orthokeratology effectively corrects moderate degree of myopia and provide excellent spectacle free day time vision without any significant adverse effects in the short term. PMID- 27257323 TI - Microsurgical free muscle flaps for reconstruction of post-traumatic complex tissue defects of foot. AB - BACKGROUND: Crush injuries of the foot often result in complex tissue loss with exposed bones and tendons. These three-dimensional defects ideally require flexible well-perfused flaps to fill the space, afford resistance to infections, and to provide supple, durable weight- and pressure-bearing surfaces. Free muscle flaps with split thickness skin graft cover have been found to have several advantages in covering three-dimensional defects with exposed tendons and bones. METHODS: All patients with post-traumatic composite tissue defects of the foot exposing bones and tendons, who presented to a tertiary care center during a 40 month period, were reconstructed with free muscle flaps as the first option. Gracilis muscle flap was used for eight patients and latissimus dorsi muscle for two patients. Decision regarding the choice of muscle was based on the size of the defect. The patients were followed up for 1 year and observed for return to activity, ability to wear footwear, requirement of secondary procedures, and any other complications. RESULTS: Ten patients presented with composite post traumatic tissue defects in the foot. All were male, with age ranging from 25 to 76 years. The defects ranged from 25 cm(2) to 225 cm(2). Free muscle transfer was successful in nine patients. Even though four required secondary flap contouring, all patients had normal weight-bearing ambulation and returned to their normal activities at 1-year follow-up. CONCLUSION: Free muscle flaps merit consideration as primary reconstructive option for post-traumatic composite tissue defects of foot. PMID- 27257324 TI - Prevalence of occult hepatitis B infection in patients visiting tertiary care hospital. AB - BACKGROUND: To study the prevalence of occult hepatitis B virus infection (OBI) in a tertiary care hospital. METHODS: 50 HBsAg negative individuals, each amongst blood donors, alcohol dependence syndrome (ADS), alcoholic cirrhotics, hepatitis C virus (HCV)/cryptogenic cirrhotics, end-stage renal disease (ESRD) on maintenance haemodialysis for one year, all malignancies prior to chemotherapy and HIV positive patients were evaluated for anti-HBc total antibody, and blood hepatitis B virus (HBV) DNA amplification in those tested positive. RESULTS: A total of 60/369 (16.2%) individuals were anti-HBc total positive, 13/50 (26%) of HCV/cryptogenic cirrhotics, 13/52 (25%) of HIV positive, 10/50 (20%) of patients with malignancy, 10/51 (19.6%) and 7/59 (11.9%) of alcoholic cirrhotics and ADS respectively had intermediate prevalence, while, blood donors 5/55 (9.1%), ESRD patients 2/52 (3.8%) had low prevalence. 12 patients (20% of all anti-HBc total positive cases) were HBV DNA positive, 5 HCV cirrhotics (10% of total HCV/cryptogenic), 4 HIV positive (7.69%), 1 each of ADS (1.69%), alcoholic cirrhotics (1.96%) and malignancy group (2%). Blood donors and ESRD patients were negative for HBV DNA. CONCLUSION: HBV DNA amplification may under diagnose OBI and anti-HBc total positivity may be a better surrogate marker. Nucleic acid testing of blood donors, however is preferred, especially in high endemic areas. OBI must be looked for in cirrhotics, HIV infection, and patients with cancers prior to chemotherapy, as they may contribute to morbidity in them. PMID- 27257325 TI - Minimal residual disease detection using flow cytometry: Applications in acute leukemia. AB - Minimal residual disease (MRD) describes disease that can be diagnosed by methodologies other than conventional morphology, and includes molecular methods (like polymerase chain reaction (PCR)) or flow cytometry (FCM). Detection and monitoring of MRD is becoming the standard of care, considering its importance in predicting the treatment outcome. MRD aids in identifying high-risk patients and hence therapy can be intensified in them while deintensification of therapy can prevent long-term sequelae of chemotherapy in low-risk category. FCM is considered as a less labor-intensive and faster MRD technique as compared to PCR although it has its own share of disadvantages. Current immune-based methodologies for detection of MRD depend on establishing leukemia-associated aberrant immunophenotype (LAIP), at diagnosis or relapse and use this information at specified time points for detection of MRD, or apply a standardized panel of antibody combinations for all MRD cases, in a different-from-normal approach. This review highlights MRD detection by FCM and its application in acute leukemia. PMID- 27257326 TI - Dengue, chikungunya ... and the missing entity - Zika fever: A new emerging threat. AB - Zika virus (ZIKV), a relative newcomer from the flavivirus group that includes dengue, Japanese encepahalitis and yellow fever, is one of the emerging pathogens that is fast transcending geographical boundaries. It is a vector-borne disease transmitted by the same Aedes aegypti and Aedes albopictus, which cause dengue and chikungunya. In addition to the vector-mediated transmission of Zika fever, probable human-to-human transmission through exchange of body fluids, including sexual and perinatal transmission and through blood transfusion, makes containment of this new entity more challenging. Moreover, a high index of suspicion by an astute physician is necessary for diagnosis of Zika fever in view of the similarity of symptoms with dengue and chikungunya, especially in areas, where these two diseases are already endemic. Zika, till recently, has had minimal impact, but its true potential is unfolding with increasing detection of congenital malformities, Guillain-Barre syndrome and other neurological and autoimmune syndromes in patients with recent history of ZIKV infection, or when mothers get infected with Zika during first or second trimester of pregnancy. The association, however, needs to be established, nonetheless it is important that we keep a close vigil on this emerging vector borne disease - the 'ZIKA' fever. PMID- 27257327 TI - Plagiarism: A silent epidemic in scientific writing - Reasons, recognition and remedies. AB - Plagiarism is one of the most serious forms of scientific misconduct prevalent today and is an important reason for significant proportion of rejection of manuscripts and retraction of published articles. It is time for the medical fraternity to unanimously adopt a 'zero tolerance' policy towards this menace. While responsibility for ensuring a plagiarism-free manuscript primarily lies with the authors, editors cannot absolve themselves of their accountability. The only way to write a plagiarism-free manuscript for an author is to write an article in his/her own words, literally and figuratively. This article discusses various types of plagiarism, reasons for increasingly reported instances of plagiarism, pros and cons of use of plagiarism detection tools for detecting plagiarism and role of authors and editors in preventing/avoiding plagiarism in a submitted manuscript. Regular usage of professional plagiarism detection tools for similarity checks with critical interpretation by the editorial team at the pre-review stage will certainly help in reducing the menace of plagiarism in submitted manuscripts. PMID- 27257328 TI - 'Peer review' for scientific manuscripts: Emerging issues, potential threats, and possible remedies. AB - Reviewers play a vital role in ensuring quality control of scientific manuscripts published in any journal. The traditional double blind peer review, although a time-tested method, has come under increasing criticism in the face of emerging trends in the review process with the primary concern being the delays in completion of the review process. Other issues are the inability to detect errors/fraud, lack of transparency, lack of reliability, potential for bias, potential for unethical practices, lack of objectivity, inconsistencies amongst reviewers, lack of recognition and motivation of reviewers. Alternative options to classical peer review being propagated are: open review, immediate self publication using preprint servers, nonselective review focusing primarily on the scientific content, and post-publication review. These alternative review processes, however, may suffer from the inability to validate quality control. In addition, anecdotal instances of peer review frauds are being reported more often than earlier. Suggested means to ensure quality of peer review process includes:(a) each journal to have its own database of reviewers, (b) verification of email IDs of reviewers provided by authors along with details of their institutions, (c) ensure credibility of reviewers before requesting for review, (d) check for plagiarism at the editorial level, (e) editors to distinguish between a good review from a possible biased/bad review, and (f) give recognition for reviewers once in a year. To conclude, quickness of review and publication should not dictate the scientific publication process at the cost of quality of contents. PMID- 27257329 TI - A clinico-epidemiological study of herpes zoster. AB - BACKGROUND: Herpes zoster is a common viral infection of skin caused by reactivation of varicella zoster virus infection from the spinal ganglia. The clinico-epidemiological patterns of this disease in an Indian setting required to be studied. METHODS: A cross sectional study was conducted on all consecutive cases of herpes zoster reporting to the Dermatology Outpatient Department at a Tertiary Care Hospital in Bangalore during a period of one year from 01 Jun 2013 to 31 May 2014. Detailed history, examination, HIV screening and Tzanck smear were carried out in all cases. RESULTS: 84 cases of herpes zoster were seen with a mean age of 30 years. Majority (39%) of cases were seen in the 21-30 year age group. Thoracic segments were involved in 65.4%, cervical in 11.9%, cranial in 11.5%, lumbar in 8.3% and sacral segments in 3.5%. 63% of cases had zoster associated pain. One case had motor involvement.3.57% of the patients were HIV positive. CONCLUSION: This study shows a lower age incidence of herpes zoster HIV positivity and zoster associated pain as compared to other studies. The pattern of segmental involvement in herpes zoster seen in this study was similar to other studies. PMID- 27257330 TI - Median Canaliform Dystrophy of Heller occurring on thumb and great toe nails. AB - Median Canaliform Dystrophy of Heller is a rare but morphologically striking habit tic deformity of thumb nails characterized by midline longitudinal furrow with multiple transverse parallel lines. The proposed etiopathogenesis is repetitive trauma to the nail plate and cuticle, however some case reports have suggested familial occurrence and use of oral retinoids in its causation. Treatment is often prolonged and unsatisfactory, though some topical agents have been used successfully. We report a case of a young male patient presenting with Median Dystrophy of Heller affecting both Great thumb and toe nails simultaneously. PMID- 27257331 TI - Large retroperitoneal filarial lymphangiectasia. PMID- 27257332 TI - Use of Ambu aScope for tracheal intubation in anticipated difficult airway, a boon. PMID- 27257333 TI - Secondary abdominal pregnancy. PMID- 27257334 TI - Post traumatic stress disorder. PMID- 27257335 TI - Syphilitic hepatitis: Look for raised alkaline phosphatase level. PMID- 27257336 TI - Rectus palsy and dengue. PMID- 27257337 TI - Fifth serotype of dengue virus: What we should prepare for? PMID- 27257338 TI - Evaluation of management of hypoglycemia in in-patients. PMID- 27257339 TI - Letter to the Editor. PMID- 27257340 TI - Kangen-karyu raises surface body temperature through oxidative stress modification. AB - Kangen-karyu, a prescription containing six herbs, has been shown to achieve its pharmacological effect through oxidative stress-dependent pathways in animal models. The aim of this study is to investigate the relationship between the antioxidative effect and pharmacological mechanisms of Kangen-karyu, specifically its body temperature elevating effect in humans. Healthy human volunteers, age 35 +/- 15 years old, were enrolled in this study. Surface body temperature, serum nitrite, reactive oxygen species (ROS) scavenging activities, and inflammatory cytokines were investigated before and 120 min after Kangen-karyu oral intake. Kangen-karyu significantly increased the surface-body temperature of the entire body; this effect was more remarkable in the upper body and continued for more than 120 min. Accompanying this therapeutic effect, serum nitrite levels were increased 120 min after oral administration. Serum ROS scavenging activities were enhanced against singlet oxygen and were concomitantly decreased against the alkoxyl radical. Serum nitrite levels and superoxide scavenging activities were positively correlated, suggesting that Kangen-karyu affects the O2 (*-)-NO balance in vivo. Kangen-karyu had no effect on IL-6, TNF-alpha and adiponectin levels. These results indicate that the therapeutic effect of Kangen-karyu is achieved through NO- and ROS-dependent mechanisms. Further, this mechanism is not limited to ROS production, but includes ROS-ROS or ROS-NO interactions. PMID- 27257341 TI - Caffeic acid phenethyl ester suppresses monocyte adhesion to the endothelium by inhibiting NF-kappaB/NOX2-derived ROS signaling. AB - Caffeic acid phenethyl ester (CAPE), one of the major polyphenols, exhibits anti oxidative, anti-bacterial, and anti-cancer properties. Atherosclerosis is a chronic inflammatory disease, the progression of which is closely related to the accumulated adhesion of inflammatory monocytes/macrophages to the endothelium. We herein determined whether CAPE and its derivatives suppressed THP-1 cell adhesion to human umbilical vein endothelial cells (HUVEC). Of the four polyphenols tested, CAPE significantly suppressed the 12-O-tetradecanoylphorbol 13-acetate (TPA)-elicited expression of cluster for differentiation (CD) 11b, 14, and 36, and this was accompanied by the inhibition of THP-1 cell adhesion to HUVEC. CAPE also suppressed the activation of TPA-elicited nuclear factor-kappaB (NF-kappaB) and accumulation of NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS), but did not affect extracellular signal-regulated kinase (ERK) phosphorylation. Taken together, these results demonstrated that CAPE suppressed THP-1 cell adhesion to HUVEC through, at least in part, the NF-kappaB, NOX2, and ROS-derived signaling axis. PMID- 27257342 TI - Reactive oxygen species induced by non-steroidal anti-inflammatory drugs enhance the effects of photodynamic therapy in gastric cancer cells. AB - Photodynamic therapy is useful for the treatment of cancer because it is minimally invasive for patients. Certain porphyrin compounds and their derivatives have been used as the photosensitizer because they accumulate specifically in cancerous tissues. However, the detailed mechanism of this phenomenon has not been clarified. We previously reported that a proton-coupled folate transporter, HCP1, transported porphyrins and that regulation of the protein was associated with cancer-specific reactive oxygen species from mitochondria (mitROS). Therefore, over-generation of mitROS could increase HCP1 expression and the effect of photodynamic therapy. We investigated whether pretreatment with indomethacin influenced photodynamic therapy by using a rat normal gastric mucosal cell line, RGM1, its cancer-like mutated cell line, RGK1, and a manganese superoxide dismutase (MnSOD)-overexpressing RGK cell line, RGK MnSOD. Indomethacin promotes the generation of cellular mitROS by inhibiting the electron transport chain, and MnSOD scavenges the mitROS. We elucidated that indomethacin enhanced cancer-specific mitROS generation and increased HCP1 expression. Furthermore, RGK1 cells showed higher cellular incorporation of hematoporphyrin and better therapeutic effect with indomethacin treatment whereas RGK-MnSOD cells did not show a difference. Thus, we concluded that indomethacin improved the effect of photodynamic therapy by inducing increased mitROS generation in cancer cells. PMID- 27257343 TI - Performance evaluation of two immunoassays for 25-hydroxyvitamin D. AB - Although immunoassays in measuring 25-hydroxyvitamin D [25(OH)D] have been improved recently, relatively large differences are still seen between results of 25(OH)D measured by immunoassays and by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the present studies, we compared two immunoassays with LC-MS/MS for measuring 25(OH)D concentrations. Concentrations of 25 hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] in serum samples from 59 healthy subjects were measured by two immunoassays including Siemens ADVIA Centaur Vitamin D Total (Centaur) and Roche Elecsys Vitamin D Total (Elecsys) and LC-MS/MS. To determine the cross reactivity of Elecsys and Centaur toward 25(OH)D2, a dosage of 200,000 IU vitamin D2 was given after first sampling. Serum samples were obtained 30 days later and concentrations of 25(OH)D2 and 25(OH)D3 were measured again. The results showed poor agreement between the immunoassays and LC-MS/MS in 25(OH)D2 and 25(OH)D3 measurements. The percentage of 25(OH)D2 cross-reactivity was 45.3% for Centaur and 41.2% for Elecsys and there was no significant difference between Centaur and Elecsys. In conclusion, Centaur and Elecsys perform unsatisfactorily in measuring 25(OH)D levels, especially for 25(OH)D2 cross-reactivity. Therefore, clinicians need to be aware of the underestimation of vitamin D status when using these immunoassays for measuring individuals supplemented with vitamin D2. PMID- 27257344 TI - Effect of quercetin and its metabolite on caveolin-1 expression induced by oxidized LDL and lysophosphatidylcholine in endothelial cells. AB - Oxidized low-density lipoprotein contributes to atherosclerotic plaque formation, and quercetin is expected to exert anti-atherosclerotic effects. We previously reported accumulation of conjugated quercetin metabolites in the aorta of rabbits fed high-cholesterol diets with quercetin glucosides, resulting in attenuation of lipid peroxidation and inhibition of lipid accumulation. Caveolin-1, a major structural protein of caveolae in vascular endothelial cells, plays a role in atherosclerosis development. Here we investigated effects of oxidized low-density lipoprotein, quercetin and its metabolite, quercetin 3-O-beta-glucuronide, on caveolin-1 expression. Oxidized low-density lipoprotein significantly upregulated caveolin-1 mRNA expression. An oxidized low-density lipoprotein component, lysophosphatidylcholine, also induced expression of both caveolin-1 mRNA and protein. However, lysophosphatidylcholine did not affect the location of caveolin 1 proteins within caveolae structures. Co-treatment with quercetin or quercetin 3 O-beta-glucuronide inhibited lysophosphatidylcholine-induced caveolin-1 expression. Quercetin and quercetin 3-O-beta-glucuronide also suppressed expression of adhesion molecules induced by oxidized low-density lipoprotein and lysophosphatidylcholine. These results strongly suggest lysophosphatidylcholine derived from oxidized low-density lipoprotein contributes to atherosclerotic events by upregulating caveolin-1 expression, resulting in induction of adhesion molecules. Quercetin metabolites are likely to exert an anti-atherosclerotic effect by attenuating caveolin-1 expression in endothelial cells. PMID- 27257345 TI - Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib. AB - Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID- 27257346 TI - Serum metabolite profiles of postoperative fatigue syndrome in rat following partial hepatectomy. AB - Postoperative fatigue syndrome is a general complication after surgery. However, there is no ''gold standard'' for fatigue assessment due to the lack of objective biomarkers. In this study, a rodent model of postoperative fatigue syndrome based on partial hepatectomy was firstly established and serum metabonomic method based on ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied. Partial least-squares discriminant analysis was used to identify the differential metabolites in 70% partial hepatectomy rats relative to sham rats and 30% partial hepatectomy rats, which showed 70% partial hepatectomy group was significantly distinguishable from 30% partial hepatectomy group and sham group. Eighteen serum metabolites responsible for the discrimination were identified. The levels of hypoxanthine, kynurenine, tryptophan, uric acid, phenylalanine, palmitic acid, arachidonic acid and oleic acid showed progressive elevation from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group, and levels of valine, tyrosine, isoleucine, linoleyl carnitine, palmitoylcarnitine, lysophosphatidylcholine (16:0), lysophosphatidylcholine (20:3), citric acid, succinic acid and hippuric acid showed progressive declining trend from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group. These potential biomarkers help to understand of etiology, pathophysiology and treatment of postoperative fatigue syndrome. PMID- 27257347 TI - Okara ameliorates glucose tolerance in GK rats. AB - Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, beta-conglycinin, and isoflavones. Although isoflavones and beta-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARgamma, adiponectin, and GLUT4, which up regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID- 27257348 TI - Dehydroepiandrosterone alters vitamin E status and prevents lipid peroxidation in vitamin E-deficient rats. AB - In humans, dehydroepiandrosterone and its sulfate ester metabolite DHEA-S are secreted predominantly from the adrenal cortex, and dehydroepiandrosterone is converted to steroid hormones, including androgens and estrogens, and neurosteroid. Dehydroepiandrosterone exerts protective effects against several pathological conditions. Although there are reports on the association between dehydroepiandrosterone and vitamins, the exact relationship between dehydroepiandrosterone and vitamin E remains to be determined. Therefore, we attempted to elucidate the effect of dehydroepiandrosterone on vitamin E status and the expression of various vitamin E-related proteins, including binding proteins, transporters, and cytochrome P450, in vitamin E-deficient rats. Plasma alpha-tocopherol levels in vitamin E-deficient rats increased in response to dehydroepiandrosterone administration. The expression of hepatic alpha-tocopherol transfer protein was repressed in vitamin E-deficient rats compared to that in control rats; however, dehydroepiandrosterone administration significantly upregulated this expression. Hepatic expression of CYP4F2, an alpha-tocopherol metabolizing enzyme, in vitamin E-deficient rats was decreased by dehydroepiandrosterone administration, whereas hepatic expression of ATP-binding cassette transporter A1, an alpha-tocopherol transporter, was not altered following dehydroepiandrosterone administration. Dehydroepiandrosterone repressed lipid peroxidation in the liver of vitamin E-deficient rats. Therefore, adequate dehydroepiandrosterone supplementation may improve lipid peroxidation under several pathological conditions, and dehydroepiandrosterone may modulate alpha tocopherol levels through altered expression of vitamin E-related proteins. PMID- 27257349 TI - Dietary patterns and changes in cardiovascular risk factors in apparently healthy Chinese women: a longitudinal study. AB - Little is known of the relationships between dietary patterns and cardiovascular risk factors in China. We therefore designed a 3-year longitudinal study to evaluate the impacts of dietary patterns on changes in these factors among Chinese women. A total of 1,028 subjects who received health examination in 2011 and 2014 were recruited. Three major dietary patterns ("vegetable pattern", "meat pattern", and "animal offal-dessert-and-alcohol pattern") were derived by principal component analysis based on validated food frequency questionnaires. Cardiovascular risk factors were standardized to create within-cohort z-scores and the changes in them were calculated as the differences between 2011 and 2014. Relationships between dietary patterns and changes in cardiovascular risk factors were assessed using general linear model. After adjustment for potential confounders, changes in total cholesterol and fasting blood glucose decreased across the tertiles of vegetable pattern (p for trend = 0.01 and 0.04, respectively). While, changes in diastolic blood pressure, total cholesterol and low density lipoprotein cholesterol increased across the tertiles of animal offal dessert-and-alcohol pattern (p for trend = 0.02, 0.01, and 0.02, respectively). The findings suggest that vegetable pattern was beneficially related to cardiovascular risk factors, whereas animal offal-dessert-and-alcohol pattern was detrimental related to these factors among apparently healthy Chinese women. PMID- 27257350 TI - Coenzyme Q10 serum concentration and redox status in European adults: influence of age, sex, and lipoprotein concentration. AB - Coenzyme Q10 (CoQ10) is synthesized in almost all human tissues and presumably involved in age-related alterations and diseases. Here, we examined the impact of aging and sex on the serum CoQ10 status in 860 European adults ranging in age from 18 to 82 years. We identified an inverse U-shaped relationship between CoQ10 concentration and age. Women showed lower cholesterol-adjusted CoQ10 levels than men, irrespective of age. As observed in both sexes, the decrease in CoQ10 concentration in older subjects was accompanied by a shift in the redox status in favour of the oxidized form. A strong positive correlation was found for total CoQ10 and cholesterol concentrations (Spearman's, p<=1E-74). We found strong negative correlations between total (Spearman's, p<=1E-07) and between cholesterol-adjusted CoQ10 concentration (Spearman's, p<=1E-14) and the proportion of the oxidized form of CoQ10. These correlations were not dependent on age and sex and were attenuated by supplementation with 150 mg/day reduced CoQ10 for 14 days. Overall, our results are useful to define risk groups with critical CoQ10 status in humans. In particular, older subjects were characterized by impaired CoQ10 status due to their lowered serum CoQ10 concentration and concomitant decrease of CoQ10 redox capacity. PMID- 27257352 TI - Global Health Education. PMID- 27257351 TI - Usefulness of computed tomography with air insufflation of the stomach prior to percutaneous endoscopic gastrostomy procedure. AB - We examined the results of computed tomography (CT) with and without air insufflation of the stomach prior to performing percutaneous endoscopic gastrostomy (PEG). We retrospectively analyzed 366 patients who underwent PEG. CT images obtained with and without air insufflation were examined for the presence or absence of contact between the gastric anterior wall and abdominal wall. PEG outcome based on CT findings was also examined. CT with and without air insufflation was performed in 272 and 94 patients, respectively. Contact between the gastric anterior wall and abdominal wall was shown in 254 (93.4%) with and 45 (47.9%) without air insufflation, all of whom underwent a successful PEG procedure. In patients without contact between the gastric anterior wall and abdominal wall, PEG was not successful in 3 of 49 (6.1%) examined by CT without and 6 of 18 (33.3%) examined with air insufflation (p = 0.004). Values for diagnostic accuracy for contact between the gastric anterior wall and abdominal wall shown by CT with and without air insufflation in successful PEG cases were 0.96 and 0.51, respectively. In conclusion, CT with air insufflation more often revealed contact between the gastric anterior wall and abdominal wall as compared to CT without air insufflation, which may help to predict PEG procedure success. PMID- 27257353 TI - Trajectories of Health and Behavioral Health Services Use among Community Corrections-Involved Rural Adults. AB - This article seeks to establish time-based trajectories of health and behavioral health services utilization for community corrections-involved (CCI) adults and to examine demographic and clinical correlates associated with these trajectories. To accomplish this aim, the authors applied a latent class growth analysis (LCGA) to services use data from a sample of rural CCI adults who reported their medical, mental health, and substance use treatment utilization behavior every 60 days for 1.5 years. LCGA established 1.5-year trajectories and demographic correlates of health services among rural CCI adults. For medical services, three classes emerged (stable-low users, 13%; stable-intermediate users, 40%; and stable-high users, 47%). For mental health and substance use services, three classes emerged (stable-low, 69% and 61%, respectively; low baseline-increase, 10% and 12%, respectively; high-baseline decline, 21% and 28%, respectively). Employment, gender, medication usage, and depression severity predicted membership across all services. Results underscore the importance of social workers and other community services providers aligning health services access with the needs of the CCI population, and highlight CCI adults as being at risk of underservice in critical prevention and intervention domains. PMID- 27257354 TI - Managing and Mentoring: Experiences of Assistant Professors in Working with Research Assistants. AB - Support from research assistants (RAs) is often framed as a resource to facilitate faculty research productivity, yet most assistant professors have received minimal training on how to effectively make use of this resource. This study collected data from a national sample of assistant professors to examine tasks RAs are asked to perform, satisfaction with RA work, challenges in working with RAs, and lessons learned to be successful. Authors used a sequential mixed methods design, first conducting a Web-based survey with 109 assistant professors in social work schools with doctoral programs, then qualitative interviews with a subset of 13 respondents who volunteered to talk more about their experiences. Evidence indicated low levels of satisfaction regarding the preparation of students for RA work, particularly among those assistant professors working with first-year doctoral students. Primary challenges included lack of student skills and commitment and sufficient time to supervise and train students. Recommendations include careful assessment of student skills at the start of the relationship and setting clear expectations. Social work programs can improve faculty-RA relationships by training new assistant professors on how to support and manage RAs and training incoming students on basic research skills for their work as RAs. PMID- 27257355 TI - The Tripod School Climate Index: An Invariant Measure of School Safety and Relationships. AB - Recently revised standards for social work practice in schools encourage data informed school climate interventions that implicitly require invariant measures of school climate. Invariant measures have the same meaning, scale, and origin across different groups of respondents. Although noninvariant measures bias statistical analyses and can lead users to erroneous conclusions, most school climate measures have not been tested for invariance. This study examines the invariance of the Tripod School Climate Index. Exploratory, confirmatory, and multiple-group confirmatory factor analyses were conducted on data collected from 66,531 students across 222 schools. Results indicate that the index is an excellent fit for the data and invariant by student grade level, demographic background, prior achievement, and dropout risk. Results imply that student responses can be validly aggregated to create school-level scores. The index will not bias studies of school climate interventions or bivariate analyses comparing perceptions of school climate across subgroups of students attending the same school. Given the centrality of school climate interventions to social work practice in schools and the consequences of noninvariance, the development of an index with these properties is an important contribution to the field. PMID- 27257356 TI - A Cross-National Validation of the Short Employment Hope Scale (EHS-14) in the United States and South Korea. AB - The Short Employment Hope Scale (EHS-14) has been developed in the United States to assess an individual's level of psychological self-sufficiency-a complementary measure to the widely used economic self-sufficiency in workforce development programs. This study examined the comparability of the EHS-14 between U.S. and South Korean low-income job seeker groups. A multisample confirmatory factor analysis (CFA) and a series of invariance tests were conducted to validate EHS-14 using two independent samples. A latent means analysis (LMA) was used to test the latent mean difference between the two samples. The results indicate that CFAs on both U.S. and South Korean samples verified the four-factor structure of EHS-14. The study also found evidence for cross-national equivalence, based on satisfying configural, metric, scalar, and factor covariance invariance. LMA results found no significant difference between the two samples. EHS-14 was found to be a reliable and valid measure with cross-cultural applicability in the South Korean socio-politico-economic context. EHS-14 can be used to benchmark the client empowerment process and monitor individualized human development paths to employment success. PMID- 27257357 TI - Tangible Needs and External Stressors Faced by Chinese American Families with a Member Having Schizophrenia. AB - This article examines the tangible needs and external stressors experienced by Chinese American families with a member living with schizophrenia, in the context of a six-month pilot study of family psychoeducation. Therapists' notes from 117 family and group sessions were analyzed. The families expressed concerns regarding housing, finance, work, study, and the shortage of bilingual psychosocial services. Interacting with government offices and social services agencies caused anxiety and frustration, partly due to the high stakes involved given their low socioeconomic status, and partly due to the bureaucracy. As immigrants, study participants had needs for language translation, knowledge about resources, and advocacy by case managers. This study also highlights the importance of interventions beyond the micro individual level to the mezzo and macro levels, where changes in organizations and policies are necessary. PMID- 27257360 TI - Grand Challenges for Social Work: Research, Practice, and Education. PMID- 27257361 TI - Interdependence between the Social and Material Convoy: Links between Volunteering, Widowhood, and Housing Transitions. AB - Relocation in older adulthood may occur due to triggering events, such as widowhood. Guided by Kahn and Antonucci's convoy model, this study explores the influence of volunteering on decision to relocate following the death of a spouse. Using three waves of data from the Health and Retirement Study (2006, 2008, and 2010), 5,146 community-dwelling married older individuals who were 65 years or older in 2008 were included. Findings from two multinomial logistic regression models showed that widows and widowers who were not volunteering in 2008 were more likely to move out of area in 2010 than their married counterparts, whereas the relationship between widowhood and relocation was not detected among those involved in volunteering. This article emphasizes the interdependency of social relationships and residences, a fundamental of one's material convoy, for older adults. Volunteering experiences may not only affect instrumental and emotional support after the loss of a key anchor in one's social convoy, but may also facilitate a widowed older adult to age in place rather than relocate. PMID- 27257362 TI - Pitfalls, Potentials, and Ethics of Online Survey Research: LGBTQ and Other Marginalized and Hard-to-Access Youths. AB - Online research methodologies may serve as an important mechanism for population focused data collection in social work research. Online surveys have become increasingly prevalent in research inquiries with young people and have been acknowledged for their potential in investigating understudied and marginalized populations and subpopulations, permitting increased access to communities that tend to be less visible-and thus often less studied-in offline contexts. Lesbian, gay, bisexual, transgender, and queer (LGBTQ) young people are a socially stigmatized, yet digitally active, youth population whose participation in online surveys has been previously addressed in the literature. Many of the opportunities and challenges of online survey research identified with LGBTQ youths may be highly relevant to other populations of marginalized and hard-to access young people, who are likely present in significant numbers in the online environment (for example, ethnoracialized youths and low-income youths). In this article, the utility of online survey methods with marginalized young people is discussed, and recommendations for social work research are provided. PMID- 27257363 TI - Correlates of Receipt of Colorectal Cancer Screening among American Indians in the Northern Plains. AB - Research has consistently documented lower colorectal cancer (CRC) screening rates for racial and ethnic minority populations, with the lowest screening rates among American Indians (AIs). Given the low CRC screening rates among AIs residing in the Northern Plains region, the objective of this research was to identify CRC screening correlates for Northern Plains AIs. With a sample of 181 AIs age 50 years or older, the authors used Andersen's behavioral model to examine the following factors related to receipt of CRC screening: (a) predisposing factors-age, education, marital status, and gender; (b) need factors personal and family history of cancer; and (c) enabling factors-having a particular place to receive medical care, annual health checkup, awareness of the availability of CRC screening, knowledge of CRC, and self-efficacy of CRC. Nested logistic regression identified the following correlates of receipt of CRC screening: (a) predisposing factors-older age; (b) need factors-having a personal history of cancer; and (c) enabling factors-having an annual health checkup, greater awareness of CRC screening, and greater self-efficacy of CRC. Given the findings, prevention and intervention strategies, including public awareness and education about CRC screening, are promising avenues to reduce cancer screening disparities among AIs. PMID- 27257364 TI - Worker Perspectives on Contemporary Milieu Therapy: A Cross-Site Ethnographic Study. AB - The term "milieu therapy" (MT) is commonly used in mental health literatures. However, because MT has historically encompassed a wide range of practices, it has invited the criticism that it is simply an attractive theoretical packaging of the time clients spend between other specified interventions, such as individual and group therapies. Some have suggested that, because of its conceptual ambiguity, MT should be abandoned altogether. Despite these challenges, MT endures as a common approach to social work practice in a range of clinical settings. This article describes a study that used ethnography to investigate the perspectives of workers from two mental health organizations that claim to provide MT. By analyzing four themes common to both sites, this article brings exploratory empirical findings to bear on the question of what constitutes MT in contemporary mental health organizations. Participants reported that (a) everything in the physical and social milieu has the potential to affect therapeutic change; (b) the milieu itself functions as a therapeutic agent; (c) the milieu provides a context for modeling and practicing desired behaviors; and (d) MT is a principle-based ethos, rather than a set of specific interventions. Implications of these findings for social work research, practice, and funding are discussed. PMID- 27257365 TI - Effects of Neighborhood Characteristics on Length of Inpatient Stay: Findings from the U.S. National Data. AB - Using a nationally representative U.S. sample, this study examined the extent to which neighborhood characteristics affected length of inpatient stay (LOS) in the United States. Data were obtained from the 2012 Area Health Resource Files. A total of 3,148 U.S. counties were included in the study. Generalized linear models and the geographically weighted regression model were used to examine the extent to which neighborhood characteristics affected LOS and its spatial variation. Exploratory spatial data analysis was also conducted to examine the geographic patterns in LOS. Hospital bed capacity was found to be the strongest predictor of LOS. Counties with a lower poverty rate, a lower uninsured rate, a higher proportion of female residents, a higher proportion of residents living in urban areas, and more diverse racial groups had a longer LOS. Significant spatial clustering pattern of LOS was also found. Findings suggest that social work professionals should be aware of spatial disparity in health care resources and develop ways of providing equitable health care for vulnerable populations in socioeconomically disadvantaged neighborhoods. PMID- 27257368 TI - Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis. AB - The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) surgery of the right ureter. The left kidney (contralateral) was used as internal control. Six rats were sham operated and used as the control group. Rats were terminated two weeks after the surgery; the kidneys were excised and precision-cut kidney slices (PCKSs) were cultured for five days in serum-free medium. Markers of collagen type I formation (P1NP), collagen type I and III degradation (C1M and C3M), and alpha-smooth muscle actin (alphaSMA) were measured in the PCKS supernatants by enzyme-linked immunosorbent assay. P1NP, C1M, C3M, and alpha-SMA were increased up to 2- to 13-fold in supernatants of tissue slices from the UUO-ligated kidneys compared with the contralateral kidneys (P < 0.001) and with the kidneys of sham operated animals (P < 0.0001). The markers could also reflect the level of fibrosis in different animals. The UUO PCKS ex vivo model provides a valuable translational tool for investigating the extracellular matrix remodeling associated with renal interstitial fibrosis. PMID- 27257369 TI - A Case of Organizing Pneumonia (OP) Associated with Pembrolizumab. AB - Until recently, chemotherapy for metastatic melanoma had disappointing results. The identification of immune checkpoints such as CTLA-4 and PD-1/PD-L1 has led to the development of an array of monoclonal antibodies (Mabs). These immunologic approaches against tumoral cells come with a novel kind of side effects that the clinician needs to be familiarized with. Herein, we report for the first time a case of organizing pneumonia, based on imaging and cytological analyses of bronchoalveolar lavage, possibly associated with the use of pembrolizumab, an anti-PD-1 Mab recently approved for the treatment of metastatic melanoma. PMID- 27257370 TI - Neurofibromatosis: an update of ophthalmic characteristics and applications of optical coherence tomography. AB - Neurofibromatosis (NF) is a multisystem disorder and tumor predisposition syndrome caused by genetic mutation on chromosome 17-17q11.2 in NF type 1 (NF1), and on chromosome 22-22q12.2 in NF type 2. The disorder is characterized by considerable heterogeneity of clinical expression. NF1 is the form with the most characteristic ocular manifestations. Lisch nodules of the iris are among the well-known diagnostic criteria for the disease. Glaucoma and associated globe enlargement have been described in a significant proportion of patients with NF1 and orbital-facial involvement. Optic nerve glioma may cause strabismus and proptosis, and palpebral neurofibroma may reach considerable size and occasionally show malignant transformation. Near infrared reflectance has greatly contributed to enhancing our knowledge on choroidal alterations in NF1. Indeed, some authors have proposed to include these among the diagnostic criteria. Optical coherence tomography has given new insight on retinal alterations and is a noninvasive tool in the management of optic nerve gliomas in children. Ocular manifestations in NF type 2 can range from early-onset cataracts in up to 80% of cases to optic nerve hamartomas and combined pigment epithelial and retinal hamartomas. PMID- 27257372 TI - Tear volume estimation using a modified Schirmer test: a randomized, multicenter, double-blind trial comparing 3% diquafosol ophthalmic solution and artificial tears in dry eye patients. AB - PURPOSE: We aimed to evaluate the feasibility of using a modified Schirmer test to determine the increase in tear volume after administration of 3% diquafosol ophthalmic solution (diquafosol 3%) in dry eye patients. PATIENTS AND METHODS: A randomized, multicenter, prospective, double-blind clinical study recruited 50 qualified subjects. They received diquafosol 3% in one eye and artificial tears in the other eye. The study protocol comprised a screening and treatment procedure completed within 1 day. The Schirmer test was performed on closed eyes three times a day. The primary efficacy end points were the second Schirmer test scores 10 minutes after the single dose. Secondary end points were the third Schirmer test scores 3 hours and 40 minutes after the single dose and the symptom scores prior to the second and third Schirmer tests. RESULTS: According to the Schirmer test, 10 minutes after administration, diquafosol 3% significantly increased tear volume compared to artificial tears. Diquafosol 3% and artificial tears both showed significant improvements in the symptom scores compared to baseline. However, there was no significant difference in the symptoms score between diquafosol 3% and artificial tears. CONCLUSION: The modified Schirmer test can detect a minute change in tear volume in dry eye patients. These findings will be useful in the diagnosis of dry eye, assessment of treatment benefits in daily clinical practice, and the development of possible tear secreting compounds for dry eye. PMID- 27257371 TI - Ocular manifestations of Sturge-Weber syndrome: pathogenesis, diagnosis, and management. AB - Sturge-Weber syndrome has been included in the group of phakomatoses that is characterized by hamartomas involving the brain, skin, and eyes. The characteristic facial port-wine stain, involving the first branch of the trigeminal nerve and the embryonic vasculature distribution in this area, leads to several ocular complications of the anterior segment and can involve the eyelids and conjunctiva. The posterior segment of the eyes is also affected with diffuse choroidal hemangiomas. However, the most frequent ocular comorbidity is glaucoma with a prevalence rate ranging from 30%-70%. Glaucoma is related to anterior chamber malformations, high episcleral venous pressure (EVP), and changes in ocular hemodynamics. Glaucoma can be diagnosed at birth, but the disease can also develop during childhood and in adults. The management of glaucoma in Sturge-Weber syndrome patients is particularly challenging because of early onset, frequently associated severe visual field impairment at the time of diagnosis, and unresponsiveness to standard treatment. Several surgical approaches have been proposed, but long-term prognosis for both intraocular pressure control and visual function remains unsatisfactory in these patients. Choroidal hemangiomas may also lead to visual impairment thorough exudative retinal detachment and macular edema. Treatment of exudative hemangioma complications is aimed at destructing the tumor or decreasing tumor leakage. PMID- 27257373 TI - The IMPACT study: a prospective evaluation of the effects of cyclosporine ophthalmic emulsion 0.05% on ocular surface staining and visual performance in patients with dry eye. AB - OBJECTIVE: The aim of this study was to evaluate the effects of cyclosporine ophthalmic emulsion 0.05% on ocular surface staining and visual performance in patients with dry eye. METHODS: This was a single-center, 6-month, open-label, Phase IV study. Patients with bilateral dry eye disease and a symptom score of >=2 on the Ocular Discomfort and 4-Symptom Questionnaire, an Ocular Surface Disease Index score of >12, at least one eye with Schirmer's score <10 mm/5 minutes, and central corneal staining graded as >=2 on the Ora CalibraTM Corneal and Conjunctival Staining Scale were enrolled. Cyclosporine ophthalmic emulsion 0.05% (Restasis((r))) was instilled twice daily in each eye. The primary efficacy endpoints were ocular surface staining and visual function at 6 months. Secondary outcome measures included Schirmer's test, tear film breakup time, symptoms, and adverse events. RESULTS: A total of 40 patients with the mean age of 59.4 years (range, 40-78 years) were enrolled; 35 (87.5%) were female and 37 (92.5%) completed the study. At 6 months, inferior corneal, central corneal, total corneal, and total ocular surface fluorescein staining were significantly improved from baseline in both eyes (P<0.001). Patient responses on the Ocular Surface Disease Index showed significant improvement in blurred vision and visual function related to reading, driving at night, working with a computer or bank machine, and watching television (P<=0.041). At 6 months, 35.1% of patients achieved >=5 mm improvement and 18.9% achieved >=10 mm improvement in the average eye Schirmer score. Mean tear film breakup time improved by >50% in both eyes (P>0.001). Patients reported significant improvement in ocular discomfort and dry eye symptoms (P<0.001). No patients discontinued treatment because of stinging or any other ocular adverse event. CONCLUSION: Dry eye patients with difficulties with day-to-day visual function demonstrated improvement in both signs and symptoms of dry eye and reported improved visual function after 6 months of treatment with cyclosporine ophthalmic emulsion 0.05%. PMID- 27257374 TI - Association of psychological factors, patients' knowledge, and management among patients with erectile dysfunction. AB - BACKGROUND: Erectile dysfunction (ED) is one of the most common health problems in men. ED can significantly affect a man's psychological well-being and overall health. PURPOSE: To investigate the association of psychological factors, patients' knowledge, and management among ED patients. PATIENTS AND METHODS: A total of 93 patients with an age range from 31 to 81 years who have undergone treatment for ED were included in this study. RESULTS: It was found that the feeling of blame (P=0.001), guilt (P=0.001), anger or bitterness (P=0.001), depression (P=0.001), feeling like a failure (P=0.001), and the feeling of letting down a partner during intercourse (P=0.001) were significantly associated with ED. Age was also found to be significantly associated with patients' psychological scale (P=0.004). In addition, the majority of patients in this study practice the right method of administration of ED therapy. However, no significant correlation was found between patients' knowledge of ED therapy and demographic characteristics. CONCLUSION: This study concluded that ED does affect psychological well-being of people. In addition, patient's knowledge about ED and its management is also crucial in ensuring that the patient achieves optimal therapeutic outcomes from ED therapy. PMID- 27257375 TI - Patient perspectives on fluticasone-vilanterol versus other corticosteroid combination products for the treatment of asthma. AB - OBJECTIVE: Fluticasone furoate (FF), an inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting beta2 receptor agonist (LABA), is a new combination used in an Ellipta((r)) device. This article compares FF-VI to other ICS-LABA combinations available, particularly emphasizing product selection from the patient perspective. DATA SOURCES: A PubMED and EMBASE search completed in October 2015 identified trials using the MeSH terms "fluticasone", "vilanterol", and "asthma". Additional information was gathered from references cited in the identified publications, the manufacturer, package insert, and ClinicalTrials.gov registry. STUDY SELECTION/DATA EXTRACTION: Preference was given to randomized controlled clinical trials. Animal trials, trials for COPD, and non-English sources were excluded. DATA SYNTHESIS: Seven efficacy trials of FF-VI in asthma were identified. Only one (24 weeks) trial compared FF-VI to another ICS-LABA combination (fluticasone propionate-salmeterol). Primary outcomes (usually lung function) and secondary outcomes (eg, quality of life and symptom scores) were comparable. In three FF-VI safety trials, the type and frequency of common adverse reactions (ie, thrush and dysphonia) were similar to those in clinical trials. Over 90% of subjects rated the Ellipta((r)) device as "easy to use" and demonstrated correct device technique initially and at 4 weeks. CONCLUSION: Individuals may have drug- and device-specific preferences that should be incorporated into therapeutic decision making. Limited data indicate that clinical and patient-oriented efficacy/safety outcomes of FF-VI are likely comparable to other available combinations for adults with asthma. Patient friendly features include once-daily dosing, flexibility of dose timing, and design/ease of the use of the device. Additional larger and long-term comparative studies are needed to determine whether these features translate into greater efficacy, safety, patient preference, or adherence versus other ICS-LABA combinations. In the next few years, the availability of less expensive generic ICS-LABA products may strongly influence patient preference. PMID- 27257376 TI - The prevalence of risk factors for cardiovascular diseases among Polish surgical patients over 65 years. AB - BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality among adults in Poland. A number of risk factors have significant influence on CVD incidence. Early identification of risk factors related to our lifestyle facilitates taking proper actions aiming at the reduction of their negative impact on health. AIM: The aim of the study was to compare the prevalence of CVD risk factors between patients aged over 65 years and patients of other age groups in surgical wards. MATERIAL AND METHODS: The study was conducted for assessment and finding the distribution of major risk factors of CVD among 420 patients aged 18-84 years who were hospitalized in surgical wards. Interview, anthropometric measurements, blood pressure, and fasting blood tests for biochemical analysis were conducted in all subjects. Statistical analysis of the material was performed using Student's t-test, chi-square test, Fisher's exact test, Mann Whitney U-test, and analysis of variance. RESULTS: While abdominal obesity (83.3%), overweight and obesity (68%), hypertension (65.1%), hypercholesterolemia (33.3%), and low level of physical activity (29.1%) were the most common CVD risk factors among patients over 65 years old, abdominal obesity (36.2%), overweight and obesity (36.1%), and current smoking were the most common CVD risk factors among patients up to the age of 35. In the age group over 65, the least prevalent risk factors for CVD were diabetes mellitus (14.8%), depressive episodes (13.6%), abuse of alcohol (11.4%), and smoking (7.8%). In the group under 35 years, we have not reported any cases of hypercholesterolemia and a lesser number of patients suffered from diabetes and HTN. CONCLUSION: Distribution of the major risk factors for CVD is quite high in the adult population, especially in the age group over 65, which can result in serious problems of health and increased rates of chronic diseases, especially CVDs. PMID- 27257377 TI - Switching to low-dose oral prolonged-release oxycodone/naloxone from WHO-Step I drugs in elderly patients with chronic pain at high risk of early opioid discontinuation. AB - PURPOSE: Chronic pain has a high prevalence in the aging population. Strong opioids also should be considered in older people for the treatment of moderate to severe pain or for pain that impairs functioning and the quality of life. This study aimed to assess the efficacy and safety of the direct switch to low-dose strong opioids (World Health Organization-Step III drugs) in elderly, opioid naive patients. PATIENTS AND METHODS: This was a single-center, retrospective, observational study in opioid-naive patients aged >=75 years, with moderate to severe chronic pain (>6-month duration) and constipation, who initiated treatment with prolonged-release oxycodone/naloxone (OXN-PR). Patients were re-evaluated after 15, 30, and 60 days (T60, final observation). Response to treatment was defined as an improvement in pain of >=30% after 30 days of therapy without worsening of constipation. RESULTS: One-hundred and eighty-six patients (mean +/- SD age 80.7+/-4.7 years; 64.5% women) with severe chronic pain (mean average pain intensity 7.1+/-1.0 on the 11-point numerical rating scale) and constipation (mean Bowel Function Index 64.1+/-24.4; 89.2% of patients on laxatives) were initiated treatment with OXN-PR (mean daily dose 11.3+/-3.5 mg). OXN-PR reduced pain intensity rapidly and was well tolerated; 63.4% of patients responded to treatment with OXN-PR. At T60 (mean daily OXN-PR dose, 21.5+/-9.7 mg), the pain intensity was reduced by 66.7%. In addition, bowel function improved (mean decrease of Bowel Function Index from baseline to T60, -28.2, P<0.0001) and the use of laxatives decreased. Already after 15 days and throughout treatment, ~70% of patients perceived their status as much/extremely improved. Only 1.6% of patients discontinued treatment due to adverse events. CONCLUSION: Low-dose OXN PR in elderly patients naive to opioids proved to be an effective option for the treatment of moderate to severe chronic pain. Large-scale trials are needed to improve clinical guidance in the assessment and treatment of pain in older people. PMID- 27257378 TI - Left ventricular structure and remodeling in patients with COPD. AB - BACKGROUND: Data on cardiac alterations such as left ventricular (LV) hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features. METHODS: Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score. RESULTS: Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT), suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that - after multivariate analysis - significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42) predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59-0.81). Patients with COPD showed right ventricular to be functional but no structural changes. CONCLUSION: Patients with COPD without evident cardiovascular disease exhibit significant changes in LV geometry, resulting in concentric remodeling. In all individuals, RWT was significantly and independently related to COPD. However, its prognostic role should be determined in future studies. PMID- 27257379 TI - Cellular uptake and fate of fibroin microspheres loaded with randomly fragmented DNA in 3T3 cells. AB - Purified fibroin protein can be obtained in large quantities from silk fibers and processed to form microscopic particles as delivery vehicles for therapeutic agents. In this study, we demonstrated that fibroin microspheres were taken up by 3T3 cells, localized in the nonlysosomal compartment, and secreted from the cytoplasm after medium replenishment. DNA-loaded microspheres were taken up by >95% of 3T3 cells. DNA cargo had no influence on the intracellular trafficking of microspheres, while fluorescently labeled cargo DNA was observed in the lysosomal compartment and in the microspheres. These results indicate that fibroin microspheres can travel through 3T3 cells without making any contact with the lysosomal compartments. The amount of DNA loaded in the microspheres taken up by 3T3 cells was estimated up to 831.0 pg/cell. Thus, fibroin microspheres can deliver a large amount of randomly fragmented DNA (<10 kb) into the cytoplasmic compartment of 3T3 cells. PMID- 27257380 TI - Spectrum of epilepsy - prevalence, impact, and treatment gap: an epidemiological study from Al-Quseir, Egypt. AB - BACKGROUND: Epidemiology continues to be an important research tool in the study of epilepsy and related disorders, providing a better understanding of the frequency, causes, and natural history of the disorder. OBJECTIVE: To estimate the prevalence of epilepsy in Al-Quseir, Red Sea Governorate, Egypt, and its magnitude of treatment gap. METHODS: The study was part of a door-to-door study, including every door, to screen all inhabitants in Al-Quseir (33,818 inhabitants) by three specialists of neurology and 15 female social workers (for demographic data collection) using a standardized screening questionnaire. All suspected cases were subjected to detailed history, clinical examination, and electroencephalogram. Neuroimaging studies and estimation of serum drug level were done in select cases if needed. RESULTS: The study revealed that the lifetime prevalence rate of epilepsy in Al-Quseir is 5.5/1,000, with the highest peak during early childhood, while that of active epilepsy is 3.3/1,000 population. The annual incidence rate is 48/100,000, and the age-specific incidence rate has a U-shaped pattern with two peaks of incidence in early infancy and elderly life. Localization-related epilepsy is the most frequently encountered type (58.8%). The treatment gap of epilepsy in Al-Quseir is 83.8%. CONCLUSION: The lifetime prevalence of epilepsy in Al-Quseir city, Red Sea Governorate, was 5.5/1000. PMID- 27257381 TI - Clinical potential of eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome. AB - Diarrhea-predominant irritable bowel syndrome (IBS-D) belongs to the group of functional gastrointestinal disorders and is characterized by abdominal pain in conjunction with diarrhea. The incidence of IBS-D is currently increasing, leading to a heavy economic burden for patients and health care systems worldwide. Recent studies suggest eluxadoline as an attractive new tool for the treatment of patients with IBS-D. Eluxadoline is an orally active MU- and kappa opioid receptor agonist and delta-opioid receptor antagonist, with powerful antidiarrheal and analgesic activity. Eluxadoline is believed to act locally in the enteric nervous system, and has no adverse effects in the central nervous system. In this review, we discuss the most recent findings on the mechanism of action of eluxadoline and the results of the clinical trials in patients with IBS D. We also discuss possible side effects and analyze the potential of eluxadoline to be used in the treatment of IBS-D. PMID- 27257382 TI - The Relationship Between Eating Disorder Symptoms and Treatment Rejection among Young Adult Men in Residential Substance Use Treatment. AB - Research has demonstrated that individuals with substance use disorders (SUDs) and comorbid mental health problems evidence heightened negative consequences, including poorer treatment outcomes, a higher risk for relapse, and mortality compared to individuals with a single disorder. In this study, we focus on the comorbidity between SUDs and eating disorder (ED) symptomatology, as EDs are similarly associated with high rates of relapse, morbidity, and mortality. Of particular importance is research examining treatment rejection among individuals in treatment for SUDs with cooccurring ED symptomatology. This study seeks to add to the literature by examining treatment rejection among young adult men in residential treatment for SUDs (N = 68) with cooccurring ED symptomatology. Results from hierarchical regression analyses indicated that ED symptoms were significantly associated with treatment rejection after controlling for alcohol and drug use and problems and depression symptoms. Although this is a preliminary study, the results add to a growing body of research examining the comorbidity between SUDs and ED symptomatology. Future research examining this relationship is needed to further elucidate the treatment patterns among individuals with comorbid ED symptoms and substance use diagnoses. PMID- 27257383 TI - Inequalities in the Impact of National Reimbursement of Smoking Cessation Pharmacotherapy and the Influence of Injunctive Norms: An Explorative Study. AB - In 2011, the Dutch government reimbursed smoking cessation pharmacotherapy with behavioral therapy for quitting smokers. We investigate whether inequalities in the use of pharmacotherapy change and, if not, whether this is due to a relatively positive injunctive norm in lower socioeconomic status (SES) groups. A total of 75,415 participants aged >=15 years from the Dutch Continuous Survey of Smoking Habits, 2009-2012, were considered with the following measures: SES (education/income), injunctive norm (mostly acceptable/neutral/mostly unacceptable), period (2011/all other years), and pharmacotherapy use (yes/no). The proportion of low SES smokers compared with high SES smokers making quit attempts with pharmacotherapy did not differ significantly. The injunctive norm of low SES smokers differed significantly from high SES smokers and nonsmokers of all SES levels. Low income smokers with mostly acceptable injunctive norms were significantly less likely to make quit attempts using pharmacotherapy than those with a neutral or less accepting injunctive norm. The significantly lower use of pharmacotherapy in quit attempts in low income smokers with a positive injunctive norm toward smoking may partly underlie the lack of uptake of reimbursed pharmacotherapy in low SES smokers. PMID- 27257384 TI - Substance Use Disorder in Early Midlife: A National Prospective Study on Health and Well-Being Correlates and Long-Term Predictors. AB - This study used national multicohort panel data from the Monitoring the Future study (N = 25,536 from senior year classes 1977-1997 followed up to the age of 35 years in 1994-2014) to examine how early midlife (age 35 years) alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with adolescent and adult sociodemographics and health and well-being risk factors. Survey items adapted from DSM-5 diagnostic criteria were used to identify individuals who (a) showed symptoms consistent with criteria for AUD or CUD at age 35 years, (b) used the substance without qualifying for a disorder (nondisordered users), and (c) abstained from using alcohol or marijuana during the past five years. At age 35 years, the estimated prevalence of past five-year AUD was 28.0%, and that of CUD was 6.1%. Multinomial logistic regressions were used to identify variations in the relative risk of disorder symptoms as a function of sociodemographic characteristics, age 18 educational and social indices and substance use, and age 35 health and satisfaction indices and substance use. In the full models, age 18 binge drinking and marijuana use were found to be among the strongest predictors of age 35 AUD and CUD, respectively. Among age 35 health and well-being indicators, lower overall health, more frequent cognitive difficulties, and lower satisfaction with spouse/partner were consistently associated with greater risks of AUD and CUD. Some evidence was found for a J-shaped association between age 35 AUD or CUD status and health and well-being indices, such that nondisordered users were sometimes better off than both abstainers and those experiencing disorder. Finally, nondisordered cannabis use, but not CUD, was found to be more common in more recent cohorts. Implications are discussed regarding the importance of placing early midlife substance use disorder within the context of both adolescent substance use and adult health and well-being. PMID- 27257385 TI - Alcohol Consumption at Any Level Increases Risk of Injury Caused by Others: Data from the Study on Global AGEing and Adult Health. AB - BACKGROUND: Alcohol use is a well-known risk factor for injury. However, information is needed about alcohol drinking patterns and the risk of injury among older adults in low- and middle-income countries as this population grows. We aimed to examine the influence of drinking patterns on the burden of injury and investigate factors associated with different types of injury in older populations in six emerging economies. METHODS: Data from more than 37,000 adults aged 50 years and older were included from the Study on Global AGEing and Adult Health (SAGE) Wave 1 conducted in six emerging economies, namely, China, Ghana, India, Mexico, Russia, and South Africa. We investigated past-year reported injuries from falls, traffic accidents, and being hit or stabbed. Alcohol drinking patterns were measured as lifetime abstinence, ever but not past- week use, and gender-specific past-week low-risk and high-risk use. We stratified by gender and used logistic regression models to observe the association between alcohol drinking pattern and risk of injury by controlling for other factors. RESULTS: During the year prior to interview, 627 (2.2%) subjects reported bodily injury resulting from a car accident, 1,156 (4.2%) from a fall, and 339 (0.9%) from being hit or stabbed during the past year. For women, only being a high-risk drinker increased the risk of being hit or stabbed, whereas for men, all levels of drinking were associated with an increased risk of being hit or stabbed. We observed a higher risk of being hit or stabbed from past-week high-risk drinking among women (odds ratio [OR] = 6.09, P < 0.01) than among men (OR = 3.57, P < 0.01). We observed no association between alcohol drinking pattern and injury due to car accidents for either women or men. CONCLUSIONS: The risk of experiencing injury due to violence increased with level of alcohol exposure of the victim. The increase in alcohol use in emerging economies calls for further study into the consequences of alcohol use and for public health initiatives to reduce the risk of violence in older adult populations, with special attention to the experience of older adult women. PMID- 27257386 TI - Methodological Issues in Predicting Pediatric Epilepsy Surgery Candidates Through Natural Language Processing and Machine Learning. AB - OBJECTIVE: We describe the development and evaluation of a system that uses machine learning and natural language processing techniques to identify potential candidates for surgical intervention for drug-resistant pediatric epilepsy. The data are comprised of free-text clinical notes extracted from the electronic health record (EHR). Both known clinical outcomes from the EHR and manual chart annotations provide gold standards for the patient's status. The following hypotheses are then tested: 1) machine learning methods can identify epilepsy surgery candidates as well as physicians do and 2) machine learning methods can identify candidates earlier than physicians do. These hypotheses are tested by systematically evaluating the effects of the data source, amount of training data, class balance, classification algorithm, and feature set on classifier performance. The results support both hypotheses, with F-measures ranging from 0.71 to 0.82. The feature set, classification algorithm, amount of training data, class balance, and gold standard all significantly affected classification performance. It was further observed that classification performance was better than the highest agreement between two annotators, even at one year before documented surgery referral. The results demonstrate that such machine learning methods can contribute to predicting pediatric epilepsy surgery candidates and reducing lag time to surgery referral. PMID- 27257387 TI - Mobile Health (mHealth) Services and Online Health Educators. AB - Mobile technology enables health-care organizations to extend health-care services by providing a suitable environment to achieve mobile health (mHealth) goals, making some health-care services accessible anywhere and anytime. Introducing mHealth could change the business processes in delivering services to patients. mHealth could empower patients as it becomes necessary for them to become involved in the health-care processes related to them. This includes the ability for patients to manage their personal information and interact with health-care staff as well as among patients themselves. The study proposes a new position to supervise mHealth services: the online health educator (OHE). The OHE should be occupied by special health-care staffs who are trained in managing online services. A survey was conducted in Brunei and Indonesia to discover the roles of OHE in managing mHealth services, followed by a focus group discussion with participants who interacted with OHE in a real online health scenario. Data analysis showed that OHE could improve patients' confidence and satisfaction in health-care services. PMID- 27257388 TI - Upregulation of Cyclooxygenase-2/Prostaglandin E2 (COX-2/PGE2) Pathway Member Multiple Drug Resistance-Associated Protein 4 (MRP4) and Downregulation of Prostaglandin Transporter (PGT) and 15-Prostaglandin Dehydrogenase (15-PGDH) in Triple-Negative Breast Cancer. AB - Elevated levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) are indicators of a poor prognosis in breast cancer. Using several independent publicly available breast cancer gene expression databases, we investigated other members of the PGE2 pathway. PGE2 is produced by COX-2 and actively exported by multiple drug resistance-associated protein 4 (MRP4) into the extracellular microenvironment, where PGE2 can bind four cognate EP receptors (EP1-EP4) and initiate diverse biological signaling pathways. Alternatively, PGE2 is imported via the prostaglandin transporter (PGT) and metabolized by 15-prostaglandin dehydrogenase (15-PGDH/HPGD). We made the novel observation that MRP4, PGT, and 15-PGDH are differentially expressed among distinct breast cancer molecular subtypes; this finding was confirmed in independent datasets. In triple-negative breast cancer, the observed gene expression pattern (high COX-2, high MRP4, low PGT, and low 15-PGDH) would favor high levels of tumor-promoting PGE2 in the tumor microenvironment that may contribute to the overall poor prognosis of triple-negative breast cancer. PMID- 27257389 TI - United airway disease: current perspectives. AB - Upper and lower airways are considered a unified morphological and functional unit, and the connection existing between them has been observed for many years, both in health and in disease. There is strong epidemiologic, pathophysiologic, and clinical evidence supporting an integrated view of rhinitis and asthma: united airway disease in the present review. The term "united airway disease" is opportune, because rhinitis and asthma are chronic inflammatory diseases of the upper and lower airways, which can be induced by allergic or nonallergic reproducible mechanisms, and present several phenotypes. Management of rhinitis and asthma must be jointly carried out, leading to better control of both diseases, and the lessons of the Allergic Rhinitis and Its Impact on Asthma initiative cannot be forgotten. PMID- 27257390 TI - Estimated hospital costs associated with preventable health care-associated infections if health care antiseptic products were unavailable. AB - OBJECTIVES: Health care-associated infections (HAIs) pose a significant health care and cost burden. This study estimates annual HAI hospital costs in the US avoided through use of health care antiseptics (health care personnel hand washes and rubs; surgical hand scrubs and rubs; patient preoperative and preinjection skin preparations). METHODS: A spreadsheet model was developed with base case inputs derived from the published literature, supplemented with assumptions when data were insufficient. Five HAIs of interest were identified: catheter associated urinary tract infections, central line-associated bloodstream infections, gastrointestinal infections caused by Clostridium difficile, hospital or ventilator-associated pneumonia, and surgical site infections. A national estimate of the annual potential lost benefits from elimination of these products is calculated based on the number of HAIs, the proportion of HAIs that are preventable, the proportion of preventable HAIs associated with health care antiseptics, and HAI hospital costs. The model is designed to be user friendly and to allow assumptions about prevention across all infections to vary or stay the same. Sensitivity analyses provide low- and high-end estimates of costs avoided. RESULTS: Low- and high-end estimates of national, annual HAIs in hospitals avoided through use of health care antiseptics are 12,100 and 223,000, respectively, with associated hospital costs avoided of US$142 million and US$4.25 billion, respectively. CONCLUSION: The model presents a novel approach to estimating the economic impact of health care antiseptic use for HAI avoidance, with the ability to vary model parameters to reflect specific scenarios. While not all HAIs are avoidable, removing or limiting access to an effective preventive tool would have a substantial impact on patient well-being and infection costs. HAI avoidance through use of health care antiseptics has a demonstrable and substantial impact on health care expenditures; the costs here are exclusive of administrative penalties or long-term outcomes for patients and caregivers such as lost productivity or indirect costs. PMID- 27257391 TI - A randomized, placebo-controlled, single-blinded, split-faced clinical trial evaluating the efficacy and safety of KLOX-001 gel formulation with KLOX light emitting diode light on facial rejuvenation. AB - PURPOSE: Many treatment modalities exist to counteract the effects of cutaneous aging. Ablative methods have been the mainstay for nonsurgical facial rejuvenation. In recent years, nonablative techniques have been developed with the aim of achieving facial rejuvenation without epidermal damage. Light-emitting diode (LED) photorejuvenation is a novel nonablative technique that induces collagen synthesis through biophotomodulatory pathways. MATERIALS AND METHODS: A single-center, randomized, single-blinded, placebo-controlled, split-faced clinical trial was designed. Thirty-two patients were enrolled for a 12-week study. Patients were randomized into one of four groups: Group A, treatment with KLOX-001 gel formulation and white LED (placebo) light; Group B, treatment with a placebo/base gel (no active chromophore) formulation and KLOX LED light; Group C, treatment with KLOX-001 gel formulation and KLOX LED light; and Group D, treatment with the standard skin rejuvenating treatment (0.1% retinol-based cream). Patients received treatment at weeks 0, 1, 2, and 3, and returned to the clinic at weeks 4, 8, and 12 for clinical assessments performed by an independent, blinded committee of physicians using subjective clinician assessment scales. Tolerability, adverse outcomes, and patient satisfaction were also assessed. RESULTS: Analysis demonstrated that the KLOX LED light with KLOX placebo/base gel and the KLOX LED light + KLOX-001 gel formulation groups were superior to standard of care and KLOX-001 gel formulation with placebo light on subjective clinical assessment and multiple wrinkle scales, with statistically significant results obtained for brow positioning, perioral wrinkling, and total wrinkle score. CONCLUSION: The study results show that KLOX LED light with KLOX 001 gel formulation and KLOX LED light with KLOX placebo/base gel are effective, safe, well-tolerated, and painless treatment modalities for skin rejuvenation. PMID- 27257393 TI - Temporal trend in the use of hysteroscopic vs laparoscopic sterilization and the characteristics of commercially insured and Medicaid-insured females in the US who have had the procedures. AB - PURPOSE: Limited research has examined the factors associated with female permanent contraception procedures. This study evaluated the temporal trend in the use of hysteroscopic sterilization (HS) vs laparoscopic sterilization (LS) and characteristics of commercially insured and Medicaid-insured women in the US who have had the procedures. METHODS: Women aged 15-49 years with claims for HS and LS procedures were identified from two MarketScan databases, one consisting of commercial claims and the other Medicaid claims, during the time period of January 1, 2003 to December 31, 2012 and January 1, 2006 to December 31, 2011, respectively. Proportions and characteristics of women who underwent HS or LS procedures were determined. Multivariable logistic regressions were used to identify characteristics associated with the use of HS vs LS. RESULTS: Commercially insured women who had HS (n=32,012) vs LS (n=64,725) were slightly older (37.2 years vs 36.4 years, respectively, P<0.001) but had similar Charlson Comorbidity Index scores. Among commercially insured women, those who had a sterilization procedure during 2008-2012 were more likely to undergo HS (odds ratio: 7.1, P<0.001) than those who had a sterilization procedure during 2003 2007. Medicaid-insured women who had HS (n=2,001) were also slightly older than women who had LS (n=12,523; 30.1 years vs 28.8 years, respectively, P<0.001) but had a higher mean Charlson Comorbidity Index score (0.32 vs 0.25, respectively, P<0.001). Among Medicaid-insured women, the likelihood of having HS vs LS increased 3.3-fold (P<0.001) in years 2009-2011 compared to years 2006-2008. Among both populations, older age, obesity, and the use of oral contraceptives within the previous 12 months were associated with having HS vs LS. CONCLUSION: Among both commercially insured and Medicaid-insured women, the likelihood of having HS vs LS increased over time. PMID- 27257392 TI - Identifying the symptom and functional domains in patients with fibromyalgia: results of a cross-sectional Internet-based survey in Italy. AB - OBJECTIVE: The aims of this cross-sectional study were to investigate the usefulness of using an Internet survey of patients with fibromyalgia in order to obtain information concerning symptoms and functionality and identify clusters of clinical features that can distinguish patient subsets. METHODS: An Internet website has been used to collect data. Fibromyalgia Impact Questionnaire Revised version, self-administered Fibromyalgia Activity Score, and Self-Administered Pain Scale were used as questionnaires. Hierarchical agglomerative clustering was applied to the data obtained in order to identify symptoms and functional-based subgroups. RESULTS: Three hundred and fifty-three patients completed the study (85.3% women). The highest scored items were those related to sleep quality, fatigue/energy, pain, stiffness, degree of tenderness, balance problems, and environmental sensitivity. A high proportion of patients reported pain in the neck (81.4%), upper back (70.1%), and lower back (83.2%). A three-cluster solution best fitted the data. The variables were significantly different (P<0.0001) among the three clusters: cluster 1 (117 patients) reflected the lowest average scores across all symptoms, cluster 3 (116 patients) the highest scores, and cluster 2 (120 patients) captured moderate symptom levels, with low depression and anxiety. CONCLUSION: Three subgroups of fibromyalgia samples in a large cohort of patients have been identified by using an Internet survey. This approach could provide rationale to support the study of individualized clinical evaluation and may be used to identify optimal treatment strategies. PMID- 27257394 TI - Persistent corneal epithelial defect responding to rebamipide ophthalmic solution in a patient with diabetes. AB - OBJECTIVE: Rebamipide ophthalmic suspension was developed for the treatment of dry eyes and for other corneal diseases, promoting the secretion of both mucin in tear fluid and membrane-associated mucin, increasing the number of goblet cells, and restoring the barrier function of the corneal epithelium. We report a case of a persistent corneal epithelial defect in a patient with diabetes treated with topical application of rebamipide ophthalmic suspension. CASE PRESENTATION: A 73 year-old woman had a history of type 2 diabetes for 35 years and nonproliferative diabetic retinopathy for 23 years. She presented to our department with discharge and ophthalmalgia in the left eye. A corneal ulcer was detected, and culture of corneal scrapings was performed, with Staphylococcus aureus and Streptococcus canis being isolated. The infection was treated with levofloxacin eye drops and ofloxacin ophthalmic ointment based on the sensitivity profile of the isolate. However, a corneal epithelial defect persisted for approximately 2 months despite continuing treatment with 0.1% hyaluronic acid ophthalmic suspension and 0.3% ofloxacin eye ointment. Her hemoglobin A1c was 7.3%. The persistent corneal epithelial defect showed improvement at 2 weeks after treatment with rebamipide unit dose 2% ophthalmic suspension, and it did not recur even when vitrectomy was subsequently performed for vitreous hemorrhage due to progression of diabetic retinopathy. CONCLUSION: This is the first report about efficacy of rebamipide unit dose 2% ophthalmic suspension for presenting persistent corneal epithelial defect in a patient with diabetes. In the present case, the suggested mechanisms are the following: improving the corneal barrier function, stabilization of mucin on the keratoconjunctival epithelium, and improving the wettability and stability of the tear film, which resulted in the promotion of healing of the corneal epithelial defect in a short time period. PMID- 27257395 TI - The Healthy Weights Initiative: a community-based obesity reduction program with positive impact on depressed mood scores. AB - OBJECTIVES: The risk for many chronic diseases increases with obesity. In addition to these, the risk for depression also increases. Exercise interventions for weight loss among those who are not overweight or obese have shown a moderate effect on depression, but few studies have looked at those with obesity. The objectives of this study were to determine 1) the prevalence of depressed mood in obese participants as determined by the Beck Depression Inventory II at baseline and follow-up; 2) the change in depressed mood between those who completed the program and those who did not; and 3) the differences between those whose depressed mood was alleviated after the program and those who continued to have depressed mood. METHODS: Depressed mood scores were calculated at baseline and follow-up for those who completed the program and for those who quit. Among those who completed the program, chi-squares were used to determine the differences between those who no longer had depressed mood and those who still had depressed mood at the end of the program, and regression analysis was used to determine the independent risk factors for still having depressed mood at program completion. RESULTS: Depressed mood prevalence decreased from 45.7% to 11.7% (P<0.000) from baseline to follow-up among those who completed the program and increased from 44.8% to 55.6% (P<0.000) among those who quit. After logistic regression, a score of <40 in general health increased the risk of still having depressed mood upon program completion (odds ratio [OR] 3.39; 95% CI 1.18-9.72; P=0.023). CONCLUSION: Treating depressed mood among obese adults through a community-based, weight-loss program based on evidence may be an adjunct to medical treatment. More research is needed. PMID- 27257396 TI - The Role of Biomarkers in Decreasing Risk of Cardiac Toxicity after Cancer Therapy. AB - With the improvement of cancer therapy, survival related to malignancy has improved, but the prevalence of long-term cardiotoxicity has also increased. Cancer therapies with known cardiac toxicity include anthracyclines, biologic agents (trastuzumab), and multikinase inhibitors (sunitinib). The most frequent presentation of cardiac toxicity is dilated cardiomyopathy associated with poorest prognosis. Monitoring of cardiac toxicity is commonly performed by assessment of left ventricular (LV) ejection fraction, which requires a significant amount of myocardial damage to allow detection of cardiac toxicity. Accordingly, this creates the impetus to search for more sensitive and reproducible biomarkers of cardiac toxicity after cancer therapy. Different biomarkers have been proposed to that end, the most studied ones included troponin release resulting from cardiomyocyte damage and natriuretic peptides reflecting elevation in LV filling pressure and wall stress. Increase in the levels of troponin and natriuretic peptides have been correlated with cumulative dose of anthracycline and the degree of LV dysfunction. Troponin is recognized as a highly efficient predictor of early and chronic cardiac toxicity, but there remains some debate regarding the clinical usefulness of the measurement of natriuretic peptides because of divergent results. Preliminary data are available for other biomarkers targeting inflammation, endothelial dysfunction, myocardial ischemia, and neuregulin-1. The purpose of this article is to review the available data to determine the role of biomarkers in decreasing the risk of cardiac toxicity after cancer therapy. PMID- 27257397 TI - Apolipoprotein E Gene Polymorphisms in Saudi Patients with Systemic Lupus Erythematosus. AB - Apolipoprotein E (APOE) is a glycosylated protein with multiple biological properties. APOE gene polymorphism plays a central role in lipid metabolism and has recently been suggested to regulate inflammation. Our objective is to evaluate whether APOE polymorphism affects susceptibility to SLE. APOE genotyping was performed using ApoE StripAssayTM kit. Results indicated significantly higher frequencies of allele epsilon4 and genotype epsilon3/epsilon4 and lower frequencies of allele epsilon3 and genotype epsilon3/epsilon3 in SLE patients than controls. APOE epsilon2 allele was found in three patients, whereas it was absent in controls. The frequencies of allele epsilon4 and genotype epsilon3/epsilon4 were significantly higher in SLE patients with renal involvement and those of alleles epsilon2, epsilon4 and genotypes epsilon2/epsilon3, epsilon3/epsilon4 were higher in patients with neuropsychiatric symptoms. It is concluded that APOE allele epsilon4 is associated with susceptibility risk/clinical manifestations of SLE and epsilon2 may increase its severity while epsilon3 is protective for SLE in Saudis. PMID- 27257398 TI - Differences among Branded Hyaluronic Acids in Italy, Part 1: Data from In Vitro and Animal Studies and Instructions for Use. AB - BACKGROUND: The use of hyaluronic acid (HA) for intra-articular (IA) injection is widespread around the world for patients affected by osteoarthritis. AIM: The aim of this study is to identify scientific evidence from in vitro and in vivo studies supporting the use of IA HAs marketed in Italy. We also evaluated the accuracy of indications and contraindications reported in the leaflets of such HAs compared with the available scientific evidence. MATERIALS AND METHODS: An extensive literature search was performed to identify all in vitro and in vivo model studies reporting on the effects of various HAs marketed in Italy for IA use. Data reported in the leaflets of different HA-based products for IA use were extracted and analyzed alongside evidence from in vitro and in vivo model studies. RESULTS: Nine in vitro studies and 11 studies on animal models were examined. Comparing results with what is reported in the leaflets of HAs marketed in Italy, it was observed that many branded formulations are introduced in the market without any reporting of basic scientific evidence. Only 12.82% and 17.95% of branded products had been shown to be effective with scientific evidence from in vitro and in vivo studies, respectively. The rationale of use of these products is based on their nature, as if a class effect existed such that all HAs would yield similar effects. CONCLUSIONS: Data on HAs deriving from in vitro and in vivo studies are scarce and relate to only a small percentage of products marketed in Italy. Many indications and contraindications are arbitrarily reported in Italian HA leaflets without the support of scientific evidence. Larger and brand-specific studies are necessary and should be reported in the leaflets to guide clinicians in making an appropriate choice regarding HA-based IA therapy. PMID- 27257399 TI - Failure of Femoral Access to Electrophysiological Evaluation Due to Aplasia of the Inferior Vena Cava. AB - We report an interesting case of a man with a persistent left superior vena cava (PLSVC) with left azygos vein who underwent electrophysiological evaluation. Further evaluation revealed congenital dilated azygos vein, while a segment connecting the inferior vena cava (IVC) to the hepatic vein and right atrium was missing. The azygos vein drained into the superior vena cava, and the hepatic veins drained directly into the right atrium. The patient did not have congenital anomalies of the remaining thoracoabdominal vasculature. PMID- 27257401 TI - Posterior Epidural Migration of a Sequestrated Lumbar Disk Fragment Causing Cauda Equina Syndrome in an Old Patient: A Case Report. AB - Disk fragment relocation is commonly limited to the anterior epidural space, although posterior epidural movement of a sequestrated disk piece to the posterior epidural space is infrequent. We present an uncommon case of dorsal extradural sequestration of lumbar disk herniation. A 77-year-old man presented with severe leg pain, low back pain, and urinary incontinence. Deep tendon reflexes were inattentive at the knee and ankle, and the motor power in terms of ankle dorsiflexion and great toe dorsiflexion was 2/5 in both lower limbs. There was hypoesthesia in the S1, S2, and S3 dermatomes. Magnetic resonance imaging displayed a large isointensity lesion at the L4-L5 level on the T2 sagittal image, indenting circumferentially the thecal sac from lateral to posterior of the thecal sac. The patient underwent an L4-L5 central laminectomy. A large, solid epidural disk fragment was recognized dorsally, with major compression of the thecal sac. The patient report improved lower extremity motor function at three-month follow-up. A displaced disk fragment should be considered as causative when patients present with cauda equine syndrome and be treated as a surgical emergency. PMID- 27257400 TI - Nearly Asymptomatic Eight-Month Thoracic Aortic Dissection. AB - Thoracic aortic dissection is a rare, but lethal, medical condition that is either misdiagnosed as a myocardial infarction or overlooked completely. Though thoracic aortic dissections are commonly diagnosed in patients exhibiting sharp chest pain, there are some notable cases where patients do not report the expected severity of pain. We report a unique case of a patient with a thoracic aortic dissection who was initially nearly asymptomatic for eight months, in order to heighten awareness, highlight diagnosis protocol, and improve prognosis for this commonly misdiagnosed, but fatal, condition. PMID- 27257402 TI - Perinatal Outcomes of Monochorionic-Diamniotic Twin Pregnancies Uncomplicated at 28 Weeks of Gestation. AB - We examined the prevalence of specific perinatal complications of monochorionic diamniotic twin pregnancies in cases without any abnormal findings until the second trimester of pregnancy. This was a retrospective cohort study performed at a tertiary perinatal center in Tokyo, Japan. There were 88 cases of uncomplicated monochorionic-diamniotic twin pregnancies at 28 weeks of gestation. In five of them (5.7%), there were serious complications associated with placental circulatory imbalance between the twins during the third trimester of pregnancy. Two cases were complicated by twin-twin transfusion syndrome, two cases were complicated by twin anemia-polycythemia sequence, and one case was complicated by acute twin-twin transfusion syndrome. In the five cases, no abnormal ultrasonographic findings or symptoms were recognized one or two weeks prior to the diagnosis. Fifty-eight cases (65.9%) were delivered at term uneventfully. Serious complications due to placental circulatory imbalance between twins occurred in about 6% of cases during the third trimester of pregnancy. PMID- 27257403 TI - Area variations in multiple morbidity using a life table methodology. AB - Analysis of healthy life expectancy is typically based on a binary distinction between health and ill-health. By contrast, this paper considers spatial modelling of disease free life expectancy taking account of the number of chronic conditions. Thus the analysis is based on population sub-groups with no disease, those with one disease only, and those with two or more diseases (multiple morbidity). Data on health status is accordingly modelled using a multinomial likelihood. The analysis uses data for 258 small areas in north London, and shows wide differences in the disease burden related to multiple morbidity. Strong associations between area socioeconomic deprivation and multiple morbidity are demonstrated, as well as strong spatial clustering. PMID- 27257404 TI - Astrophysical flows near [Formula: see text] gravity black holes. AB - In this paper, we study the accretion process for fluids flowing near a black hole in the context of f(T) teleparallel gravity. Specifically, by performing a dynamical analysis by a Hamiltonian system, we are able to find the sonic points. After that, we consider different isothermal test fluids in order to study the accretion process when they are falling onto the black hole. We find that these flows can be classified according to the equation of state and the black hole features. Results are compared in f(T) and f(R) gravity. PMID- 27257405 TI - Comparison of the 2D and 3D Nanostructured Lectin-Based Biosensors for In Situ Detection of Sialic Acid on Glycoproteins. AB - We present here comparison of a build-up of two ultrasensitive lectin biosensors based on 2D or 3D architecture. A 2D lectin biosensor was prepared by a covalent immobilisation of lectin Sambucus nigra agglutinin (SNA) recognising sialic acid directly on a mixed self-assembled monolayer (SAM) on planar gold surfaces. A 3D biosensor was prepared by covalent immobilisation of SNA lectin on a mixed SAM layer formed on gold nanoparticles. Surface plasmon resonance technique allowed to follow kinetics of a mixed SAM (1:1 mixture of 11-mercaptoundecanoic acid and 6-mercaptohexanol) formation on a bare gold electrode and on an electrode modified by 5 nm and 20 nm gold nanoparticles (AuNPs). Results from the study revealed that a mixed SAM formation is slower on surfaces with increased curvature, the process of SAM formation on all surfaces is completed within 6 min, but a density of thiols on such surfaces differs significantly. Quartz crystal microbalance experiments showed that a surface density of immobilised lectin of (2.53 +/- 0.01) pmol cm-2 was higher on planar gold surface compared to the surface modified by 20 nm AuNPs with a surface density of (0.94 +/- 0.01) pmol cm-2. Even though a larger amount of SNA lectin was immobilised on a surface of the 2D biosensor compared to the 3D biosensor, lectin molecules immobilised on AuNPs were more accessible for its analytes - glycoproteins fetuin and asialofetuin, containing different amount of sialic acid on the protein surface. Most likely a better accessibility of lectin for its analytes on a 3D surface and proper interfacial properties of a 3D surface are behind unprecedented detection limit down to aM level for the lectin biosensor based on such a nanoscale tuned interface. PMID- 27257406 TI - How does collegial support increase retention of registered nurses in homecare nursing agencies? a qualitative study. AB - BACKGROUND: Collegial workplace support has been linked to higher registered nurse (RN) retention in various clinical settings. In Japan, homecare agencies experience high RN turnover. The purpose of this study was to develop a conceptual framework to describe how perceived support from colleagues affects RNs' decision to remain in an agency. METHODS: A qualitative research method based on grounded theory was used. Participants were RNs with at least 4 years of experience at the same homecare agency. Participants were theoretically sampled via managers of 12 homecare nursing agencies. Semi-structured interviews and supplementary participant observations were conducted. Data were analyzed using a constant comparative technique, and the process of how workplace support affected participants' decision to remain at their agency was clarified. RESULTS: In total, 26 RNs were interviewed, 23 of whom were observed in their practice setting. Participants' perception of support from colleagues was framed as being "encouraged to grow in one's own way", which comprised practicing with protected autonomy in an insight-producing environment. Participants reported that they were able to practice with protected autonomy, receiving 1) mindful monitoring, 2) semi-independent responsibility, 3) help as needed, and 4) collegial empathy and validation. RNs also felt supported in an insight-producing environment by 1) enlightening dialogue, 2) being set for one's next challenges, and 3) being able to grow at one's own pace. Reportedly, these were defining characteristics in their decision to continue working in their agencies. CONCLUSIONS: For RNs to willingly stay at a homecare nursing agency, it is essential that they are able to practice with protected autonomy in an insight-producing environment that encourages them to grow in their own way. Further research is needed to explore ways to create and enhance such environments to lower RN turnover. PMID- 27257408 TI - Article Watch: July 2016. AB - This column highlights recently published articles that are of interest to the readership of this publication. We encourage ABRF members to forward information on articles they feel are important and useful to Clive Slaughter, MCG-UGA Medical Partnership, 1425 Prince Ave., Athens, GA 30606, USA. Tel: (706) 713 2216; Fax: (706) 713-2221; E-mail: cslaught@uga.edu, or to any member of the editorial board. Article summaries reflect the reviewer's opinions and not necessarily those of the association. PMID- 27257407 TI - Estimating average alcohol consumption in the population using multiple sources: the case of Spain. AB - BACKGROUND: National estimates on per capita alcohol consumption are provided regularly by various sources and may have validity problems, so corrections are needed for monitoring and assessment purposes. Our objectives were to compare different alcohol availability estimates for Spain, to build the best estimate (actual consumption), characterize its time trend during 2001-2011, and quantify the extent to which other estimates (coverage) approximated actual consumption. METHODS: Estimates were: alcohol availability from the Spanish Tax Agency (Tax Agency availability), World Health Organization (WHO availability) and other international agencies, self-reported purchases from the Spanish Food Consumption Panel, and self-reported consumption from population surveys. Analyses included calculating: between-agency discrepancy in availability, multisource availability (correcting Tax Agency availability by underestimation of wine and cider), actual consumption (adjusting multisource availability by unrecorded alcohol consumption/purchases and alcohol losses), and coverage of selected estimates. Sensitivity analyses were undertaken. Time trends were characterized by joinpoint regression. RESULTS: Between-agency discrepancy in alcohol availability remained high in 2011, mainly because of wine and spirits, although some decrease was observed during the study period. The actual consumption was 9.5 l of pure alcohol/person-year in 2011, decreasing 2.3 % annually, mainly due to wine and spirits. 2011 coverage of WHO availability, Tax Agency availability, self reported purchases, and self-reported consumption was 99.5, 99.5, 66.3, and 28.0 %, respectively, generally with downward trends (last three estimates, especially self-reported consumption). The multisource availability overestimated actual consumption by 12.3 %, mainly due to tourism imbalance. CONCLUSIONS: Spanish estimates of per capita alcohol consumption show considerable weaknesses. Using uncorrected estimates, especially self-reported consumption, for monitoring or other purposes is misleading. To obtain conservative estimates of alcohol attributable disease burden or heavy drinking prevalence, self-reported consumption should be shifted upwards by more than 85 % (91 % in 2011) of Tax Agency or WHO availability figures. The weaknesses identified can probably also be found worldwide, thus much empirical work remains to be done to improve estimates of per capita alcohol consumption. PMID- 27257409 TI - Wrangling Big Data Through Diversity, Research Education and Partnerships. PMID- 27257410 TI - The prediction of virus mutation using neural networks and rough set techniques. AB - Viral evolution remains to be a main obstacle in the effectiveness of antiviral treatments. The ability to predict this evolution will help in the early detection of drug-resistant strains and will potentially facilitate the design of more efficient antiviral treatments. Various tools has been utilized in genome studies to achieve this goal. One of these tools is machine learning, which facilitates the study of structure-activity relationships, secondary and tertiary structure evolution prediction, and sequence error correction. This work proposes a novel machine learning technique for the prediction of the possible point mutations that appear on alignments of primary RNA sequence structure. It predicts the genotype of each nucleotide in the RNA sequence, and proves that a nucleotide in an RNA sequence changes based on the other nucleotides in the sequence. Neural networks technique is utilized in order to predict new strains, then a rough set theory based algorithm is introduced to extract these point mutation patterns. This algorithm is applied on a number of aligned RNA isolates time-series species of the Newcastle virus. Two different data sets from two sources are used in the validation of these techniques. The results show that the accuracy of this technique in predicting the nucleotides in the new generation is as high as 75 %. The mutation rules are visualized for the analysis of the correlation between different nucleotides in the same RNA sequence. PMID- 27257411 TI - A rare 47 XXY/46 XX mosaicism with clinical features of Klinefelter syndrome. AB - BACKGROUND: 47 XXY/46 XX mosaicism with characteristics suggesting Klinefelter syndrome is very rare and at present, only seven cases have been reported in the literature. CASE PRESENTATION: We report an Indian boy diagnosed as variant of Klinefelter syndrome with 47 XXY/46 XX mosaicism at age 12 years. He was noted to have right cryptorchidism and chordae at birth, but did not have surgery for these until age 3 years. During surgery, the right gonad was atrophic and removed. Histology revealed atrophic ovarian tissue. Pelvic ultrasound showed no Mullerian structures. There was however no clinical follow up and he was raised as a boy. At 12 years old he was re-evaluated because of parental concern about his 'female' body habitus. He was slightly overweight, had eunuchoid body habitus with mild gynaecomastia. The right scrotal sac was empty and a 2mls testis was present in the left scrotum. Penile length was 5.2 cm and width 2.0 cm. There was absent pubic or axillary hair. Pronation and supination of his upper limbs were reduced and x-ray of both elbow joints revealed bilateral radioulnar synostosis. The baseline laboratory data were LH < 0.1 mIU/ml, FSH 1.4 mIU/ml, testosterone 0.6 nmol/L with raised estradiol, 96 pmol/L. HCG stimulation test showed poor Leydig cell response. The karyotype based on 76 cells was 47 XXY[9]/46 XX[67] with SRY positive. Laparoscopic examination revealed no Mullerian structures. CONCLUSION: Insisting on an adequate number of cells (at least 50) to be examined during karyotyping is important so as not to miss diagnosing mosaicism. PMID- 27257412 TI - Prostate-specific antigen nadir after high-dose-rate brachytherapy predicts long term survival outcomes in high-risk prostate cancer. AB - PURPOSE: To evaluate the prognostic value of prostate-specific antigen nadir (nPSA) after high-dose-rate (HDR) brachytherapy in clinically non-metastatic high risk prostate cancer patients. MATERIAL AND METHODS: Data from 216 patients with high-risk or locally advanced prostate cancer who underwent HDR brachytherapy and external beam radiation therapy with long-term androgen deprivation therapy (ADT) between 2003 and 2008 were analyzed. The median prostate-specific antigen (PSA) level at diagnosis was 24 ng/ml (range: 3-338 ng/ml). The clinical stage was T1c 2a in 55 cases (26%), T2b-2c in 48 (22%), T3a in 75 (35%), and T3b-4 in 38 (17%). The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After 5 fractions, external beam radiation therapy with 10 fractions of 3 Gy was administered. All patients initially underwent neoadjuvant ADT for at least 6 months, and adjuvant ADT was continued for 36 months. The median follow-up was 7 years from the start of radiotherapy. RESULTS: The 7-year PSA relapse-free rate among patients with a post-radiotherapy nPSA level of <= 0.02 ng/ml was 94%, compared with 23% for patients with higher nPSA values (HR = 28.57; 95% CI: 12.04-66.66; p < 0.001). Multivariate analysis revealed that the nPSA value after radiotherapy was a significant independent predictor of biochemical failure, whereas pretreatment predictive values for worse biochemical control including higher level of initial PSA, Gleason score >= 8, positive biopsy core rate >= 67%, and T3b-T4, failed to reach independent predictor status. The 7-year cancer-specific survival rate among patients with a post radiotherapy nPSA level of <= 0.02 ng/ml was 99%, compared with 82% for patients with higher nPSA values (HR = 32.25; 95% CI: 3.401-333.3; p = 0.002). CONCLUSIONS: A post-radiotherapy nPSA value of <= 0.02 ng/ml was associated with better long-term biochemical tumor control even if patients had pretreatment predictive values for worse control. PMID- 27257413 TI - Single-fraction high-dose-rate brachytherapy using real-time transrectal ultrasound based planning in combination with external beam radiotherapy for prostate cancer: dosimetrics and early clinical results. AB - PURPOSE: To validate the feasibility of a single-fraction high-dose-rate brachytherapy (HDRBT) boost for prostate cancer using real-time transrectal ultrasound (TRUS) based planning. MATERIAL AND METHODS: From August 2012 to September 2015, 126 patients underwent a single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning. External beam radiation therapy (EBRT) (37.5 Gy/15 fractions, 44 Gy/22 fractions, or 45 Gy/25 fractions) was performed before (31%) or after (69%) HDRBT boost. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were assessed 4 and 12 months after the end of combined treatment using the international prostate symptom score scale (IPSS) and the common terminology criteria for adverse events (CTCAE) v3.0. RESULTS: All dose-planning objectives were achieved in 90% of patients. Prostate D90 >= 105% and <= 115% was achieved in 99% of patients, prostate V150 <= 40% in 99%, prostate V200 < 11% in 96%, urethra D10 < 120% for 99%, urethra V125 = 0% in 100%, and rectal V75 < 1 cc in 93% of patients. Median IPSS score was 4 at baseline and did not change at 4 and 12 months after combined treatment. No patients developed >= grade 2 GI toxicity. With a median follow-up of 10 months, only two patients experienced biochemical failure. Among patients who didn't receive ADT, cumulative percentage of patients with PSA <= 1 ng/ml at 4 and 18 months was respectively 23% and 66%. CONCLUSIONS: Single-fraction HDRBT boost of 15 Gy using real-time TRUS based planning achieves consistently high dosimetry quality. In combination with EBRT, toxicity outcomes appear promising. A longer follow-up is needed to assess long-term outcome and toxicities. PMID- 27257414 TI - Template guided transperineal saturation biopsy of the prostate: lessons for focal and urethra-sparing high-dose-rate brachytherapy for localized prostate cancer. AB - PURPOSE: The aim of this work is to evaluate results of prostate transperineal saturation biopsy as a guide for focal high-dose-rate brachytherapy in patients with prostate cancer (PCa). MATERIAL AND METHODS: Template guided saturation biopsy was performed in 67 primary patients with suspicion for prostate cancer. Biopsy was performed under ultrasonography (US) control with the help of brachytherapy grid and 5 mm distance between samples. We put special attention for accurate sampling of prostate in periurethral region. The number of cores varied from 17 to 81 (average 36 cores). Finally, in 40 patients with confirmed prostate cancer results of biopsy were used for brachytherapy planning. RESULTS: Saturation biopsy revealed prostate cancer in 40 of 67 evaluated patients. The extent of biopsy core involvement varied from 5% to 100% (average: 57%). Focal nature of PCa (single unilateral tumor nodule) was diagnosed in 10 (25%), multifocal - in another 30 (75%) patients. Hemigland invasion was mentioned in 12 (30%) cases. Saturation biopsy detected PCa in periurethral cores in 27 (67.5%) of 40 evaluated patients. In 10 patients, the extent of involvement in periurethral cores varied between 10% and 50%; in another, 17 observations exceeded 50%. According to results obtained on saturation biopsy, we performed HDR brachytherapy with "urethra low dose tunnel" (D10ur <= 80-90%) in 13 patients with noninvolved periurethral cores. Theoretically, hemigland brachytherapy was possible in 12 of 40 evaluated patients with PCa. CONCLUSIONS: In low risk patients with PCa results of template guided saturation biopsy indicates high frequency (75%) of multifocal disease and high probability (67.5%) of periurethral invasion. Suitable candidates for focal HDR brachytherapy or irradiation with additional sparing of urethra can be effectively determined with the help of saturation biopsy. PMID- 27257415 TI - Multi-catheter interstitial brachytherapy for partial breast irradiation: an audit of implant quality based on dosimetric evaluation comparing intra-operative versus post-operative placement. AB - PURPOSE: The use of multicatheter interstitial brachytherapy (MIB) for accelerated partial breast irradiation (APBI) in early breast cancer (EBC) patients outside the trial setting has increased. Hence, there is a need to critically evaluate implant quality. Moreover, there is a scarcity of reports using an open cavity technique. We report the dosimetric indices of open and closed cavity MIB techniques. MATERIAL AND METHODS: The dosimetric parameters of 60 EBC patients treated with MIB (open and closed cavity) who underwent three dimensional, computerized tomography (CT) based planning for APBI from November 2011 to July 2015 were evaluated. Coverage Index (CI), Dose Homogeneity Index (DHI), Conformity Index (COIN), Plan Quality Index (PQI), and Dose Non-uniformity Index (DNR) were assessed. RESULTS: Forty-one patients underwent open cavity and 19 patients underwent closed cavity placement of brachytherapy catheters. The median number of planes was 4 and median number of needles was 20. Median dose was 34 Gy with dose per fraction of 3.4 Gy, given twice a day, 6 hours apart. The D90 of the cavity and clinical target volume (CTV) were 105% and 89%, respectively. The median doses to the surgical clips were greater than 100%. The median CI of the cavity and CTV was 0.96 and 0.82, respectively. The DHI and COIN index of the CTV was 0.73 and 0.67. There were no significant differences in the dosimetric parameters based on whether the technique was done open or closed. CONCLUSIONS: Critical evaluation of the dosimetric parameters of MIB-APBI is important for optimal results. While the open and closed techniques have similar dosimetry, our institutional preference is for an open technique which eases the procedure due to direct visualization of the tumor cavity. PMID- 27257416 TI - Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer. AB - PURPOSE: The purpose of this study was to demonstrate the dosimetric and clinical feasibility of image guided radiation therapy (IGRT) combined with high-dose-rate (HDR) intracavitary brachytherapy (ICBT) to improve dose distribution in cervical cancer treatment. MATERIAL AND METHODS: For 42 cervical cancer patients, magnetic resonance imaging (MRI) scans were acquired after completion of whole pelvic irradiation 45-46 Gy and 5 fractions of B + I (ICBT + IGRT) treatment were subsequently received. The high risk clinical target volume (HRCTV), intermediate risk clinical target volume (IRCTV), bladder, rectum, and sigmoid were contoured on the computed tomography (CT) scans. The total planning aim doses for HRCTV was D90% > 85 Gy, whilst constraints for rectum and sigmoid were D2cc < 75 Gy and D2cc < 90 Gy for bladder in terms of an equivalent dose in 2 Gy (EQD2) for external beam radiotherapy (EBRT) and brachytherapy boost. The IGRT plan was optimized on top of the ICBT dose distribution. A dosimetric comparison was made between B + I and optimized ICBT (O-ICBT) only. RESULTS: The mean D90% of HRCTV was comparable for B + I and O-ICBT (p = 0.82). For B + I plan, HRCTV D100%, IRCTV D100%, and IRCTV D90% were significantly increased by a mean of 10.52 Gy, 5.61 Gy, and 2.70 Gy, respectively (p < 0.01). The D2cc for bladder, rectum, and sigmoid were lower by a mean of 21.36, 6.78, and 10.65 Gy, respectively (p < 0.01). The mean rectum V60 Gy value over 42 patients was almost the same for both techniques but for bladder and sigmoid B + I had higher V60 Gy mean values as compared with the O-ICBT. CONCLUSIONS: B + I can improve dose distribution in cervical cancer treatment; it could be useful for tumors extended beyond the reach of intracavitary/interstitial brachytherapy (IC/ISBT) or for centers that are inexperienced or ill-equipped with IC/ISBT techniques. Additional confirmatory prospective studies with larger numbers of patients and longer follow-up are required to validate the durability. PMID- 27257417 TI - Survey on gynecological cancer treatment by Piedmont, Liguria, and Valle d'Aosta group of AIRO (Italian Association of Radiation Oncology). AB - PURPOSE: We focused the attention on radiation therapy practices about the gynecological malignancies in Piedmont, Liguria, and Valle d'Aosta to know the current treatment practice and to improve the quality of care. MATERIAL AND METHODS: We proposed a cognitive survey to evaluate the standard practice patterns for gynecological cancer management, adopted from 2012 to 2014 by radiotherapy (RT) centers with a large amount of gynecological cancer cases. There were three topics: 1. Taking care and multidisciplinary approach, 2. Radiotherapy treatment and brachytherapy, 3. Follow-up. RESULTS: Nineteen centers treated gynecological malignancies and 12 of these had a multidisciplinary dedicated team. Radiotherapy option has been used in all clinical setting: definitive, adjuvant, and palliative. In general, 1978 patients were treated. There were 834 brachytherapy (BRT) treatments. The fusion between diagnostic imaging (magnetic resonance imaging - MRI, positron emission tomography - PET) and computed tomography (CT) simulation was used for contouring in all centers. Conformal RT and intensity modulated radiation therapy (IMRT) were the most frequent techniques. The image guided radiation therapy (IGRT) was used in 10/19 centers. There were 8 active BRT centers. Brachytherapy was performed both with radical intent and as boost, mostly by HDR (6/8 centers). The doses for exclusive BRT were between 20 to 30 Gy. The doses for BRT boost were between 10 and 20 Gy. Four centers used CT-MRI compatible applicators but only one used MRI for planning. The BRT plans on vaginal cuff were still performed on traditional radiographies in 2 centers. The plan sum was evaluated in only 1 center. Only 1 center performed in vivo dosimetry. CONCLUSIONS: In the last three years, multidisciplinary approach, contouring, treatment techniques, doses, and control systems were similar in Liguria-Piedmont and Valle d'Aosta. However, the technology implementation didn't translate in a real treatment innovation so far. PMID- 27257418 TI - Optimum organ volume ranges for organs at risk dose in cervical cancer intracavitary brachytherapy. AB - PURPOSE: To analyze the optimum organ filling point for organs at risk (OARs) dose in cervical cancer high-dose-rate (HDR) brachytherapy. MATERIAL AND METHODS: In a retrospective study, 32 locally advanced cervical cancer patients (97 insertions) who were treated with 3D conformal external beam radiation therapy (EBRT) and concurrent chemotherapy during 2010-2013 were included. Rotterdam HDR tandem-ovoid applicators were used and computed tomography (CT) scanning was performed after each insertion. The OARs delineation and GEC-ESTRO-based clinical target volumes (CTVs) contouring was followed by 3D forward planning. Then, dose volume histogram (DVH) parameters of organs were recorded and patients were classified based on their OARs volumes, as well as their inserted tandem length. RESULTS: The absorbed dose to point A ranged between 6.5-7.5 Gy. D0.1cm(3) and D2cm(3) of the bladder significantly increased with the bladder volume enlargement (p value < 0.05). By increasing the bladder volume up to about 140 cm(3), the rectum dose was also increased. For the cases with bladder volumes higher than 140 cm(3), the rectum dose decreased. For bladder volumes lower than 75 cm(3), the sigmoid dose decreased; however, for bladder volumes higher than 75 cm(3), the sigmoid dose increased. The D2cm(3) of the bladder and rectum were higher for longer tandems than for shorter ones, respectively. The divergence of the obtained results for different tandem lengths became wider by the extension of the bladder volume. The rectum and sigmoid volume had a direct impact on increasing their D0.1cm(3) and D2cm(3) , as well as decreasing their D10, D30, and D50. CONCLUSIONS: There is a relationship between the volumes of OARs and their received doses. Selecting a bladder with a volume of about 70 cm(3) or less proved to be better with regards to the dose to the bladder, rectum, and sigmoid. PMID- 27257419 TI - Impact of heterogeneity-corrected dose calculation using a grid-based Boltzmann solver on breast and cervix cancer brachytherapy. AB - PURPOSE: To analyze the impact of heterogeneity-corrected dose calculation on dosimetric quality parameters in gynecological and breast brachytherapy using Acuros, a grid-based Boltzmann equation solver (GBBS), and to evaluate the shielding effects of different cervix brachytherapy applicators. MATERIAL AND METHODS: Calculations with TG-43 and Acuros were based on computed tomography (CT) retrospectively, for 10 cases of accelerated partial breast irradiation and 9 cervix cancer cases treated with tandem-ring applicators. Phantom CT-scans of different applicators (plastic and titanium) were acquired. For breast cases the V20Gyalphabeta3 to lung, the D0.1cm(3) , D1cm(3) , D2cm(3) to rib, the D0.1cm(3) , D1cm(3) , D10cm(3) to skin, and Dmax for all structures were reported. For cervix cases, the D0.1cm(3) , D2cm(3) to bladder, rectum and sigmoid, and the D50, D90, D98, V100 for the CTVHR were reported. For the phantom study, surrogates for target and organ at risk were created for a similar dose volume histogram (DVH) analysis. Absorbed dose and equivalent dose to 2 Gy fractionation (EQD2) were used for comparison. RESULTS: Calculations with TG-43 overestimated the dose for all dosimetric indices investigated. For breast, a decrease of ~8% was found for D10cm(3) to the skin and 5% for D2cm(3) to rib, resulting in a difference ~ -1.5 Gy EQD2 for overall treatment. Smaller effects were found for cervix cases with the plastic applicator, with up to -2% (-0.2 Gy EQD2) per fraction for organs at risk and -0.5% (-0.3 Gy EQD2) per fraction for CTVHR. The shielding effect of the titanium applicator resulted in a decrease of 2% for D2cm(3) to the organ at risk versus 0.7% for plastic. CONCLUSIONS: Lower doses were reported when calculating with Acuros compared to TG-43. Differences in dose parameters were larger in breast cases. A lower impact on clinical dose parameters was found for the cervix cases. Applicator material causes systematic shielding effects that can be taken into account. PMID- 27257420 TI - Image-guided high-dose-rate interstitial brachytherapy - a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer. AB - PURPOSE: To report the treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC). CASE REPORT: This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive (131)I, the lesion expanded as 3.7 * 3.0 * 2.3 cm(3) and 2.0 * 1.5 * 1.5 cm(3). The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. RESULTS: Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. CONCLUSIONS: The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC. PMID- 27257421 TI - Dose reconstruction technique using non-rigid registration to evaluate spatial correspondence between high-dose region and late radiation toxicity: a case of tracheobronchial stenosis after external beam radiotherapy combined with endotracheal brachytherapy for tracheal cancer. AB - PURPOSE: Small organ subvolume irradiated by a high-dose has been emphasized to be associated with late complication after radiotherapy. Here, we demonstrate a potential use of surface-based, non-rigid registration to investigate how high dose volume topographically correlates with the location of late radiation morbidity in a case of tracheobronchial radiation stenosis. MATERIAL AND METHODS: An algorithm of point set registration was implemented to handle non-rigid registration between contour points on the organ surfaces. The framework estimated the global correspondence between the dose distribution and the varying anatomical structure. We applied it to an 80-year-old man who developed tracheobronchial stenosis 2 years after high-dose-rate endobronchial brachytherapy (HDR-EBT) (24 Gy in 6 Gy fractions) and external beam radiotherapy (EBRT) (40 Gy in 2 Gy fractions) for early-stage tracheal cancer. RESULTS AND CONCLUSIONS: Based on the transformation function computed by the non-rigid registration, irradiated dose distribution was reconstructed on the surface of post-treatment tracheobronchial stenosis. For expressing the equivalent dose in a fractional dose of 2 Gy in HDR-EBT, alpha/beta of linear quadratic model was assumed as 3 Gy for the tracheal bronchus. The tracheobronchial surface irradiated by more than 100 Gyalphabeta3 tended to develop severe stenosis, which attributed to a more than 50% decrease in the luminal area. The proposed dose reconstruction technique can be a powerful tool to predict late radiation toxicity with spatial consideration. PMID- 27257422 TI - Erratum: A total EQD2 greater than 85 Gy for trachea and main bronchus D2cc being associated with severe late complications after definitive endobronchial brachytherapy. AB - [This corrects the article DOI: 10.5114/jcb.2015.54968.]. PMID- 27257423 TI - Opioid Drugs in Patients With Liver Disease: A Systematic Review. AB - CONTEXT: The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients. EVIDENCE ACQUISITION: This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles. RESULTS: In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered. CONCLUSIONS: Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased, the initial dose must be decreased, the intervals between doses should be increased and some patients need to be continuously assessed. PMID- 27257424 TI - Economic Burden of Hepatitis C Virus Infection in Different Stages of Disease: A Report From Southern Iran. AB - BACKGROUND: Hepatitis C virus (HCV) infection is a major blood-borne infection which imposes high economic cost on the patients. OBJECTIVES: The current study aimed to evaluate the total annual cost due to chronic HCV related diseases imposed on each patient and their family in Southern Iran. PATIENTS AND METHODS: Economic burden of chronic hepatitis C-related liver diseases (chronic hepatitis C, cirrhosis and hepatocellular carcinoma) were examined. The current retrospective study evaluated 200 Iranian patients for their socioeconomic status, utilization (direct and indirect costs) and treatment costs and work days lost due to illness by a structured questionnaire in 2015. Costs of hospital admissions were extracted from databases of Nemazee hospital, Shiraz, Iran. The outpatient expenditure per patient was measured through the rate of outpatient visits and average cost per visit reported by the patients; while the inpatient costs were calculated through annual rate of hospital admissions and average expenditure. Self-medication and direct non-medical costs were also reported. The human capital approach was used to measure the work loss cost. RESULTS: The total annual cost per patient for chronic hepatitis C, cirrhosis and hepatocellular carcinoma (HCC) based on purchasing power parity (PPP) were USD 1625.50, USD 6117.2, and USD 11047.2 in 2015, respectively. CONCLUSIONS: Chronic hepatitis C related liver diseases impose a substantial economic burden on patients, families and the society. The current study provides useful information on cost of treatment and work loss for different disease states, which can be further used in cost-effectiveness evaluations. PMID- 27257425 TI - Tumor Necrosis Factor-alpha-308 G/A Polymorphisms and Risk of Hepatocellular Carcinoma: A Meta-Analysis. AB - CONTEXT: Hepatocellular carcinoma (HCC) is a common disorder throughout the world that can develop due to various factors, including genetics. Tumor necrosis factor-alpha (TNF-alpha) is the most frequently studied cytokine related to the risk of developing HCC, and an association between the 308 position of the TNF alpha promoter (TNF-alpha-308) and HCC risk has been confirmed in various reports. EVIDENCE ACQUISITION: The PubMed, Scopus, and Google Scholar databases were searched through July 12, 2015, for studies on associations between TNF alpha-308 and the risk of HCC. To determine this association, odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 23 case-control studies were investigated, involving 3,389 cases and 4,235 controls. The overall conclusion was that the A allele was more frequent in case groups compared to control groups (13.4% vs. 8.4%). Thus, the A allele was significantly associated with increased HCC risk (OR = 1.77; 95% CI = [1.26-2.50]; P value < 0.002). In addition to the allelic model, the dominant model (AA + AG vs. GG) was significantly associated with HCC risk (OR = 1.80; CI = [1.29-2.51]; P value < 0.001). In the sensitivity analysis for co-dominant (AA vs. GG) and recessive models (AA vs. AG + GG), no trustworthy associations with the risk of HCC development were observed. CONCLUSIONS: This meta-analysis indicated that the TNF alpha-308 G/A polymorphism is significantly associated with increased susceptibility to HCC. However, to confirm this finding, more studies are needed on TNF-alpha-308 G/A polymorphisms associated with HCC. PMID- 27257426 TI - Leptin Receptor Gene Polymorphisms and the Risk of Non-Alcoholic Fatty Liver Disease and Coronary Atherosclerosis in the Chinese Han Population. AB - BACKGROUND: Leptin receptor (LEPR) polymorphisms have been reported to be associated with lipid metabolism and insulin resistance in various populations. However, whether LEPR polymorphisms are associated with the risks of non alcoholic fatty liver disease (NAFLD) and coronary atherosclerosis in the Chinese Han population remains unknown. OBJECTIVES: To investigate the association of LEPR polymorphisms at Q223R and K109R with the risks of NAFLD and coronary atherosclerosis in the Chinese Han population. PATIENTS AND METHODS: Genotypes of LEPR Q223R and K109R were determined by polymerase chain reaction followed by sequencing in patients with NAFLD (n = 554), coronary atherosclerosis (n = 421), and healthy controls (n = 550). Serum lipid profiles were determined using biochemical methods. Pearson's chi(2) test was used to check for Hardy-Weinberg equilibrium and to analyze the distributions of genotypes' alleles between groups. Baseline characteristics were analyzed using student's t-test, paired samples t-test, or the chi(2) test where appropriate. RESULTS: The LEPR Q223R A allele significantly reduced the risks of both NAFLD and coronary atherosclerosis (OR = 0.683, 95% CI: 0.527 - 0.884, P = 0.004 and OR = 0.724, 95% CI: 0.548 - 0.955, P = 0.022, respectively). Compared to controls, no significant differences in the genotype and allele frequencies of K109R were found in the NAFLD and coronary atherosclerosis populations, respectively. However, there was a significantly increased risk of coronary atherosclerosis in NAFLD patients who carried the K109R A allele (OR = 2.283, 95% CI: 1.556 - 3.348, P < 0.001). CONCLUSIONS: LEPR Q223R polymorphisms may confer a significant risk of NAFLD and coronary atherosclerosis. The A allele in the K109R polymorphism might be considered an independent risk factor for coronary atherosclerosis in NAFLD patients. PMID- 27257427 TI - Efficacy of PEGylated Interferon in Treatment-Experienced Chinese Patients With HBeAg Positive Chronic Hepatitis B. AB - BACKGROUND: After treatment cessation, a high prevalence of relapse was reported in chronic hepatitis B (CHB) patients in China, especially in nucleot(s)ide analogues (NUCs)-experienced patients. Re-treatment for these patients remains unsolved. OBJECTIVES: This study aims to evaluate the efficacy of PEGylated interferon in HBeAg positive patients with exposure to antiviral therapy. PATIENTS AND METHODS: A total of 55 treatment-experienced, HBeAg positive Chinese patients were enrolled in this study. Of these patients, 33 were NUCs-experienced and 22 were interferon-experienced. PEGylated interferon was administered to 34 patients; and 21 patients were retreated with conventional interferon. RESULTS: Of the 34 treatment-experienced patients who received PEGylated interferon, 52.9% achieved virologic response, and 41.2% achieved HBeAg loss and seroconversion. Patients who were treated with PEGylated interferon for 48 weeks achieved higher virologic response (80%); HBeAg loss (60%); HBeAg seroconversion (60%); and HBsAg loss (5%) than patients treated for 24 weeks with PEGylated interferon. Their responses were also higher than those who were treated with conventional interferon. HBeAg seroconversion in treatment-experienced patients was independently associated with 48-week PEGylated interferon therapy duration. CONCLUSIONS: PEGylated interferon was effective in treatment-experienced patients with HBeAg positive CHB, and showed higher rates of virological response, HBeAg loss, and seroconversion. The results provide important information regarding the role of re-treatment with PEGylated interferon in treatment-experienced HBeAg positive patients. PMID- 27257428 TI - Hepatitis B Virus Infection in the General Population of Iran: An Updated Systematic Review and Meta-Analysis. AB - CONTEXT: The hepatitis B virus (HBV) is a major global public health problem, affecting more than 2 billion people worldwide. Accurate and updated data on HBV prevalence is important for further planning to control the infection. The aim of this study was to update the prevalence estimate of HBV infection in the general population of Iran. EVIDENCE ACQUISITION: A systematic review was done for data on the prevalence of HBV infection in the general Iranian population published between Jan. 1, 1990, and Jan. 1, 2016, in both international and national databases, including PubMed, Scopus, Web of Science, Scientific Information Database, IranMedex, and Magiran. All papers with clearly described time and location of the study, proper sampling strategies, and proper analysis methods were included in the present study. Data were extracted by two independent reviewers. Prevalence of HBV infection with a 95% confidence interval (CI) was calculated using Stata software, version 13. RESULTS: The polled estimated prevalence of HBV infection in the general population of Iran was 2.2 % (95% CI: 1.9% - 2.6%). The highest prevalence of HBV infection (8.9%, 95% CI: 7.6% - 10.2%) was reported from Golestan province, and the lowest prevalence (0.7%, 95% CI: 0.4% - 1.1%) was seen in Kermanshah province. The prevalence of HBV infection was estimated at 3% (95% CI: 2.2% - 3.8%) for Iranian males and 1.7% (95% CI: 1.2% - 2.3%) for Iranian females. The prevalence of HBV infection in the general population of Iran was 2.9% (95% CI: 2.5% - 3.4%) before 2010 and 1.3% (95% CI: 0.9% - 1.7%) after 2010. CONCLUSIONS: In total, Iran was classified within the low-intermediate HBV prevalence areas (2% - 4%), while according to recent data (after 2010), Iran was classified within the low HBV prevalence areas (< 2%), indicating that preventive measures conducted in Iran have been effective. PMID- 27257430 TI - Vaccination Against Hepatitis A for Hemophilic Patients: Is It Necessary? AB - BACKGROUND: Hemophilic patients require long-life intravenous infusion of factor concentrates to treat bleedings. This could increase the risk of transmission of blood-borne infections like hepatitis C. OBJECTIVES: The current study was aimed at investigating the immunity status against hepatitis A in hemophilic patients in south Khorasan and evaluating the necessity of hepatitis A vaccination for this population. PATIENTS AND METHODS: A cross-sectional descriptive study was conducted between 2014 and 2015 on all hemophilic patients of south Khorasan province, Iran (n = 108) for anti-HAV total, anti- HCV, HBs-Ag, anti-HIV, and anti-HTLV-I /II. Note that no one had already received a hepatitis A vaccine. RESULTS: As our results show, 77.8% of the participants (59% under 20 and 88.4% above 20 years old) were seropositive for anti-HAV total; 20.4% and 2.8% (three patients) of the cases were anti-HCV positive and anti-HTLV-1 positive, respectively, while none of the subjects were HBS-Ag or HIV-Ab positive. Seventeen of the patients (15.75%) showed a co-infection of HAV with HCV, and five HCV-infected patients (22.73%) had no immunity against hepatitis A. There was a significant relationship between age, rural life, and anti-HAV positive state in our patients (P < 0.001). No significant relationship between positive anti-HAV status and sex (P = 0.16), severity of hemophilia (P = 0.23), and infection with HIV, HCV, HTLV-1, and hepatitis B (P > 0.05) was detected. CONCLUSIONS: More than 40% of the hemophilic patients under 20 years of age in the present study had no immunity against hepatitis A, and 23% of hepatitis C patients had not had a hepatitis A co-infection yet. Since hepatitis A can show a fulminant course in hepatitis C patients, vaccination against hepatitis A seems necessary in hemophilic patients in the region. PMID- 27257429 TI - Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review-Screened. AB - CONTEXT: Due to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-alpha) inhibitors, and other common immunosuppressive agents in various conditions. EVIDENCE ACQUISITION: Through an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr. RESULTS: It was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-alpha inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of immunosuppressive drugs. However, the optimal time of prophylaxis keeping should be increased in cases associated with rituximab or hematopoietic stem cell transplants. According to the latest studies and guidelines from different bodies, recommendations regarding screening, monitoring, and management of HBVr are outlined. CONCLUSIONS: Identification of patients at the risk of HBVr before immunosuppressive therapy is an undeniable part of treatment. Starting the antiviral therapy, based on the type of immunosuppressive drugs and the underlying disease, could lead to better management of disease. PMID- 27257431 TI - Mate-guarding behavior enhances male reproductive success via familiarization with mating partners in medaka fish. AB - BACKGROUND: Male-male competition and female mating preference are major mechanisms of sexual selection, which influences individual fitness. How male male competition affects female preference, however, remains poorly understood. Under laboratory conditions, medaka (Oryzias latipes) males compete to position themselves between a rival male and the female (mate-guarding) in triadic relationships (male, male, and female). In addition, females prefer to mate with visually familiar males. In the present study, to examine whether mate-guarding affects female preference via visual familiarization, we established a novel behavioral test to simultaneously quantify visual familiarization of focal males with females and mate-guarding against rival males. In addition, we investigated the effect of familiarization on male reproductive success in triadic relationships. RESULTS: Three fish (female, male, male) were placed separately in a transparent three-chamber tank, which allowed the male in the center (near male) to maintain closer proximity to the female than the other male (far male). Placement of the wild-type male in the center blocked visual familiarization of the far male by the female via mate-guarding. In contrast, placement of an arginine-vasotocin receptor mutant male, which exhibits mate-guarding deficits, in the center, allowing for maintaining close proximity to the female, did not block familiarization of the far male by the female. We also demonstrated that the reproductive success of males was significantly decreased by depriving females visual familiarization with the males. CONCLUSIONS: Our findings indicated that, at least in triadic relationships, dominance in mate-guarding, not simply close proximity, allows males to gain familiarity with the female over their rivals, which may enhance female preference for the dominant male. These findings focusing on the triadic relationships of medaka may contribute to our understanding of the adaptive significance of persistent mate-guarding, as well as female preference for familiar mates. PMID- 27257432 TI - Erratum to: Poor prognostic factors in patients who underwent surgery for acute non-occlusive ischemic colitis. AB - [This corrects the article DOI: 10.1186/s13017-015-0003-z.]. PMID- 27257433 TI - A Case of Epididymo-orchitis after intravesical bacille Calmette-Guerin therapy for superficial bladder carcinoma in a patient with latent tuberculosis infection. AB - BACKGROUND: Intravesical instillation of bacille Calmette-Guerin (BCG) has been established as efficient therapy for superficial bladder carcinoma. Overall, intravesical BCG is well tolerated and results in complications of less than 5 %. However, adverse effects such as granulomatous prostatitis, pneumonitis, hepatitis, sepsis, and hypersensitivity reactions may occur. The reported rate for tuberculous orchitis after BCG intravesical therapy is 0.4 %. FINDINGS: We report a case of monolateral tuberculous orchitis occurring one month after the second course of intravescical instillation of bacille Calmette-Guerin in a patient with proven superficial bladder carcinoma and latent tuberculosis infection. CONCLUSIONS: In our opinion intravesical instillation of BCG should be considered on an individual patient basis, with full patient disclosure of the potentially significant risks. A screening with an intradermal Mantoux before starting the first cycle of BCG instillation should be recommended and isoniazid would be indicated as the treatment for latent tuberculosis infection. PMID- 27257434 TI - Mental health services and R&D in South Korea. AB - World Health Organization has asserted that mental illness is the greatest overriding burden of disease in the majority of developed countries, and that the socioeconomic burden of mental disease will exceed that of cancer and cardiovascular disorders in the future. The life-time prevalence rate for mental disorders in Korea is reported at 27.6 %, which means three out of 10 adults experience mental disorders more than once throughout their lifetime. Korea's suicide rate has remained the highest among Organization for Economic Cooperation and Development (OECD) nations for 10 consecutive years, with 29.1 people out of every 100,000 having committed suicide. Nevertheless, a comprehensive study on the mental health services and the Research and Development (R&D) status in Korea is hard to find. Against this backdrop, this paper examines the mental health services and the R&D status in Korea, and examines their shortcomings and future direction. The paper discusses the mental health service system, budget and human resources, followed by the mental health R&D system and budget. And, by a comparison with other OECD countries, the areas for improvement are discussed and based on that, a future direction is suggested. This paper proposes three measures to realize mid and long-term mental health promotion services and to realize improvements in mental health R&D at the national level: first, establish a national mental health system; second, forecast demand for mental health; and third, secure and develop mental health professionals. PMID- 27257435 TI - Simultaneous achievement of high ethanol yield and titer in Clostridium thermocellum. AB - BACKGROUND: Biofuel production from plant cell walls offers the potential for sustainable and economically attractive alternatives to petroleum-based products. Fuels from cellulosic biomass are particularly promising, but would benefit from lower processing costs. Clostridium thermocellum can rapidly solubilize and ferment cellulosic biomass, making it a promising candidate microorganism for consolidated bioprocessing for biofuel production, but increases in product yield and titer are still needed. RESULTS: Here, we started with an engineered C. thermocellum strain where the central metabolic pathways to products other than ethanol had been deleted. After two stages of adaptive evolution, an evolved strain was selected with improved yield and titer. On chemically defined medium with crystalline cellulose as substrate, the evolved strain produced 22.4 +/- 1.4 g/L ethanol from 60 g/L cellulose. The resulting yield was about 0.39 gETOH/gGluc eq, which is 75 % of the maximum theoretical yield. Genome resequencing, proteomics, and biochemical analysis were used to examine differences between the original and evolved strains. CONCLUSIONS: A two step selection method successfully improved the ethanol yield and the titer. This evolved strain has the highest ethanol yield and titer reported to date for C. thermocellum, and is an important step in the development of this microbe for industrial applications. PMID- 27257436 TI - Engineering Bacillus licheniformis for the production of meso-2,3-butanediol. AB - BACKGROUND: 2,3-Butanediol (2,3-BD) can be used as a liquid fuel additive to replace petroleum oil, and as an important platform chemical in the pharmaceutical and plastic industries. Microbial production of 2,3-BD by Bacillus licheniformis presents potential advantages due to its GRAS status, but previous attempts to use this microorganism as a chassis strain resulted in the production of a mix of D-2,3-BD and meso-2,3-BD isomers. RESULTS: The aim of this work was to develop an engineered strain of B. licheniformis suited to produce the high titers of the pure meso-2,3-BD isomer. Glycerol dehydrogenase (Gdh) was identified as the catalyst for D-2,3-BD biosynthesis from its precursor acetoin in B. licheniformis. The gdh gene was, therefore, deleted from the wild-type strain WX-02 to inhibit the flux of acetoin to D-2,3-BD biosynthesis. The acoR gene involved in acetoin degradation through AoDH ES was also deleted to provide adequate flux from acetoin towards meso-2,3-BD. By re-directing the carbon flux distribution, the double-deletion mutant WX-02DeltagdhDeltaacoR produced 28.2 g/L of meso-2,3-BD isomer with >99 % purity. The titer was 50 % higher than that of the wide type. A bench-scale fermentation by the double-deletion mutant was developed to further improve meso-2,3-BD production. In a fed-batch fermentation, meso-2,3-BD titer reached 98.0 g/L with a purity of >99.0 % and a productivity of 0.94 g/L-h. CONCLUSIONS: This work demonstrates the potential of producing meso 2,3-BD with high titer and purity through metabolic engineering of B. licheniformis. PMID- 27257437 TI - The efficacy of thuricin CD, tigecycline, vancomycin, teicoplanin, rifampicin and nitazoxanide, independently and in paired combinations against Clostridium difficile biofilms and planktonic cells. AB - BACKGROUND: Thuricin CD is a two-component antimicrobial, belonging to the recently designated sactibiotic subclass of bacteriocins. The aim of this study was to investigate the effects of thuricin CD, as well as the antibiotics, tigecycline, vancomycin, teicoplanin, rifampicin and nitazoxanide when used independently and when combined at low concentrations on the viability of Clostridium difficile 20291 R027, TL178 R002, Liv022 R106, DPC6350 and VPI10463 biofilms and planktonic cells. RESULTS: On the basis of XTT (2,3-bis[2-methyloxy 4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide)-menadione biofilm viability assays, we found that thuricin CD was effective against biofilms of R027, Liv022 R106 and DPC6350 when used independently while nitazoxanide and rifampicin were also potent against biofilms of R027 and DPC6350, when applied on their own. Tigecycline was found to be effective against R027 and DPC6350 biofilms, whereas teicoplanin and vancomycin when used independently were only effective against DPC6350 biofilms. The efficacies of the antibiotics rifampicin, tigecycline, vancomycin and teicoplanin against C. difficile 20291 R027 biofilms were significantly potentiated when combined with thuricin CD, indicating effective antimicrobial combinations with this sactibiotic against R027 biofilms. However, the potency of nitazoxanide against R027 biofilms was significantly diminished when combined with thuricin CD, indicating an ineffective combination with this sactibiotic against R027 biofilms. Paired combinations of thuricin CD along with these five antibiotics were effective at diminishing the viability of DPC6350 biofilms. However, such combinations were largely ineffective against biofilms of TL178 R002, Liv022 R106 and VPI10463. CONCLUSIONS: To the best of our knowledge, this is the first study to highlight the activity of a sactibiotic bacteriocin against biofilms and the first to reveal the potency of the antibiotics tigecycline, teicoplanin and nitazoxanide against C. difficile biofilms. On the basis of this study, it is apparent that different strains of C. difficile possess varying abilities to form biofilms and that the sensitivities of these biofilms to different antimicrobials and antimicrobial combinations are strain-dependent. Since the formation of relatively strong biofilms by certain C. difficile strains may contribute to increased cases of antibiotic resistance and recurrence and relapse of C. difficile infection, the findings presented in this study could provide alternative strategies to target this pathogen. PMID- 27257438 TI - Prevalence, genotyping and risk factors of thermophilic Campylobacter spreading in organic turkey farms in Germany. AB - BACKGROUND: The need for organic food of animal origin has increased rapidly in recent years. However, effects of organic animal husbandry on food safety have not been rigorously tested especially in meat turkey flocks. This study provides for the first time an overview on the prevalence and genetic diversity of Campylobacter species (spp.) in five organic meat turkey farms located in different regions in Germany, as well as on potential risk factors of bacterial spreading. Thirty cloacal swabs as well as water samples and darkling beetles were collected from each flock and examined for the presence of Campylobacter by conventional and molecular biological methods. The isolates were genotyped by flaA-RFLP. RESULTS: Campylobacter spp. were detected in cloacal swabs in all 5 turkey flocks with prevalence ranged from 90.0 to 100 %. 13 cloacal swabs collected from birds in farm III and IV were harboured mixed population of thermophilic campylobacters. In total, from 158 Campylobacter isolated from turkeys 89 (56.33 %) were identified as C. coli and 69 (43.76 %) as C. jejuni. Three Campylobacter (2 C. jejuni and 1 C. coli) were detected in drinkers of two farms and 3 C. coli were isolated from darkling beetles of one farm. No Campylobacter were isolated from main water tanks. flaA-RFLP assay showed that turkey farms can harbour more than one genotype. In a single turkey two different genotypes could be detected. The genotypes of campylobacters isolated from water samples or beetles were identical with those isolated from turkeys. No effect was found of some environmental parameters [ammonia concentration (NH3), carbon dioxide concentration (CO2), relative humidity (RH) and air temperature)] on Campylobacter prevalence in organic turkey farms. Additionally, drinking water and darkling beetles might be considered as risk factors for the spreading of Campylobacter in turkey flocks. CONCLUSIONS: This study highlights the high prevalence and genotypic diversity of Campylobacter spp. isolated from organic turkey flocks. Further research is needed to assess other potential risk factors responsible for bacteria spreading in order to mitigate the spread of Campylobacter in organic turkey flocks by improving biosecurity control measures. PMID- 27257439 TI - Assessment of recovery in older patients hospitalized with different diagnoses and functional levels, evaluated with and without geriatric assessment. AB - BACKGROUND: The objective of the present study was to investigate 1) the role of different admission diagnoses and 2) the degree of functional loss, on the rate of recovery of older patients after acute hospitalization. Furthermore, to compare the predictive value of simple assessments that can be carried out in a hospital lacking geriatric service, with assessments including geriatric screening tests. METHODS: Prospective, observational cohort study, including 961community dwelling patients aged >= 70 years, transferred from medical, cardiac, pulmonary and orthopedic acute hospital departments to intermediate care in nursing home. Functional assessment with Barthel index (BI) was performed at admission to the nursing home and further geriatric assessment tests was performed during the first week. Logistic regression models with and without geriatric assessment were compared concerning the patients having 1) slow recovery (nursing home stay up to 2 months before return home) or, 2) poor recovery (dead or still in nursing home at 2 months). RESULTS: Slow recovery was independently associated with a diagnosis of non-vertebral fracture, BI subgroups 50-79 and <50, and, in the model including geriatric assessment, also with cognitive impairment. Poor recovery was more complex, and independently associated both with BI < 50, receiving home care before admission, higher age, admission with a non-vertebral fracture, and in the geriatric assessment model, cognitive impairment. CONCLUSIONS: Geriatric assessment is optimal for determining the recovery potential of older patients after acute hospitalization. As some hospitals lack geriatric services and ability to perform geriatric screening tests, a simpler assessment based on admission diagnoses and ADL function (BI), gives good information regarding the possible rehabilitation time and possibility to return home. PMID- 27257440 TI - Trusted Autonomy and Cognitive Cyber Symbiosis: Open Challenges. AB - This paper considers two emerging interdisciplinary, but related topics that are likely to create tipping points in advancing the engineering and science areas. Trusted Autonomy (TA) is a field of research that focuses on understanding and designing the interaction space between two entities each of which exhibits a level of autonomy. These entities can be humans, machines, or a mix of the two. Cognitive Cyber Symbiosis (CoCyS) is a cloud that uses humans and machines for decision-making. In CoCyS, human-machine teams are viewed as a network with each node comprising humans (as computational machines) or computers. CoCyS focuses on the architecture and interface of a Trusted Autonomous System. This paper examines these two concepts and seeks to remove ambiguity by introducing formal definitions for these concepts. It then discusses open challenges for TA and CoCyS, that is, whether a team made of humans and machines can work in fluid, seamless harmony. PMID- 27257441 TI - Passing the Turing Test Does Not Mean the End of Humanity. AB - In this paper we look at the phenomenon that is the Turing test. We consider how Turing originally introduced his imitation game and discuss what this means in a practical scenario. Due to its popular appeal we also look into different representations of the test as indicated by numerous reviewers. The main emphasis here, however, is to consider what it actually means for a machine to pass the Turing test and what importance this has, if any. In particular does it mean that, as Turing put it, a machine can "think". Specifically we consider claims that passing the Turing test means that machines will have achieved human-like intelligence and as a consequence the singularity will be upon us in the blink of an eye. PMID- 27257442 TI - Erratum to: The integrative epigenomic-transcriptomic landscape of ER positive breast cancer. PMID- 27257444 TI - Does a Journal Have an Ethical Monitoring Duty? AB - Research and ethics are inseparable. Based on abhorrent research abuses under the cloak of scientific enquiry, development of the process for the ethical overview of research on/with humans was undertaken. By the end of the twentieth century, sufficient and extensive local and international principles, guidelines, legislations, and treaties about research on humans were in place, with all human based research requiring review by independent research ethics committees (RECs). With so much established knowledge and legislation about the ethical management of the research process and REC oversight, is there a role for journal editorial boards in ethical oversight? Recommendations from the International Committee of Medical Journal Editors, the basis of the editorial policies of the IJTMB, include the requirement that research must be approved by an REC, and documentation of that review should be included in each article. Thus, as a minimum, journals must ensure that any research submitted for publication has had appropriate ethical review. But journals receive manuscripts after research is done. Journals, therefore, have a duty to ensure that received manuscripts meet expected standards for the publication of research and, for nonresearch situations, that appropriate protections of the research participants were in place even though REC review was not involved. PMID- 27257443 TI - Contemporary management of TMJ involvement in JIA patients and its orofacial consequences. AB - Juvenile idiopathic arthritis is the most common chronic rheumatic condition during childhood. Temporomandibular joint arthritis is frequently asymptomatic. When it takes place during childhood, it may affect condylar growth; therefore, these children are at risk of unfavorable long-term outcomes from the associated joint damage. The etiology is not completely understood, but it is considered as multifactorial with both genetic and environmental factors involved. The standardized examination and imaging protocols serve important purpose to diagnose temporomandibular joint (TMJ) arthritis not only to establish an early interventional strategy but also to assess craniofacial growth and the progression of signs and symptoms in those patients. Although the treatment of juvenile idiopathic arthritis (JIA) has changed dramatically over the last decades due to new therapeutic options, TMJ arthritis still can develop during the course of the disease. In clinical experience, TMJs appear to respond less well to the standard of care used to treat other joints. More individualized approach to the patient's treatment serves as the main goal of personalized medicine. It could be achieved by adopting new methods of medical imaging such as conebeam computer tomography as well as developing reliable biomarkers which may assist with predicting disease type, course, or severity and predicting response to medication. This article provides an overview of current information on orofacial complications in JIA and its management. Based on information provided in this review, more precise diagnosis, proper tools for recognizing people at risk, and more efficient treatment approaches could be implemented. This may lead to more personalized treatment management strategies of TMJ complications of JIA patients. PMID- 27257445 TI - Intradialytic Massage for Leg Cramps Among Hemodialysis Patients: a Pilot Randomized Controlled Trial. AB - BACKGROUND: Patients on hemodialysis often experience muscle cramps that result in discomfort, shortened treatment times, and inadequate dialysis dose. Cramps have been associated with adversely affecting sleep and health-related quality of life, depression and anxiety. There is limited evidence available about massage in dialysis; however, massage in cancer patients has demonstrated decreases in pain, inflammation, and feelings of anxiety. These correlations indicate massage may be an effective treatment modality for hemodialysis-related lower extremity cramping. PURPOSE: To determine the effectiveness of intradialytic massage on the frequency of cramping among hemodialysis patients prone to lower extremity cramping. PARTICIPANTS: 26 maintenance hemodialysis patients with frequent lower extremity cramps. SETTING: three outpatient hemodialysis centers in Northeast Ohio. RESEARCH DESIGN: randomized controlled trial. INTERVENTION: The intervention group received a 20-minute massage of the lower extremities during each treatment (three times per week) for two weeks. The control group received usual care by dialysis center staff. MAIN OUTCOME MEASURE: change in frequency of lower leg cramping. RESULTS: Patient reported cramping at home decreased by 1.3 episodes per week in the intervention group compared to 0.2 episodes per week in the control group (p=.005). Patient reported cramping during dialysis decreased by 0.8 episodes in the intervention group compared to 0.4 episodes in the control group (p=0.44). CONCLUSION: Intradialytic massage appears to be an effective way to address muscle cramping. Larger studies with longer duration should be conducted to further examine this approach. PMID- 27257446 TI - Dynamic Angular Petrissage as Treatment for Axillary Web Syndrome Occurring after Surgery for Breast Cancer: a Case Report. AB - BACKGROUND: In the context of breast cancer, axillary web syndrome (AWS), also called lymphatic cording, typically presents in the weeks after axillary surgery. This painful condition, likely lymphofibrotic in origin, restricts upper extremity range of motion (ROM). There is no established treatment, although physical therapy and other approaches have been used to variable effect. This report describes treatment of a female client with AWS, who had recently undergone a unilateral simple mastectomy with sentinel node biopsy plus axillary dissection. METHODS: The client presented with pain upon movement (self-reported as 5 on the 0-10 Oxford Pain Scale), visible cording and restricted use of the ipsilateral upper extremity. Clinical assessment included determining the extent of AWS cording (taut, from axilla to wrist) and measuring glenohumeral joint ROM (140 degrees flexion by goniometer). A therapeutic massage with movement protocol, termed dynamic angular petrissage, was administered over two sessions: Swedish massage combined with dynamically taking the limb through all possible angles of movement (passive ROM), controlling stretch and tension while simultaneously and segmentally applying petrissage and non-petrissage techniques to the underlying soft tissue. Careful attention was taken to not break the cord. Home care consisted of prescribed exercises performed by the patient. RESULTS: After Session One, pain was reduced (to 0/10), ROM improved (to 170 degrees flexion), and cording was visibly reduced. After Session Two the cord was residually apparent only on hyperextension, with no ROM restrictions in glenohumeral joint flexion. Follow-up at three months revealed absence of visual or palpable evidence of cording, unrestricted glenohumeral joint ROM, and absence of movement-associated pain. CONCLUSION: The signs and symptoms of AWS were quickly and effectively eliminated, without causing any pain or discomfort to the client. We propose that dynamic angular petrissage may be an efficient and safe treatment approach for reducing the pain, mobility restrictions, and cording of AWS. PMID- 27257447 TI - Primary pleuropulmonary synovial sarcoma mimicking a carcinoid tumor: Case report and literature review. AB - Primary pleuropulmonary synovial sarcoma is a rare malignancy. Commonly described radiologic features in the literature include pleural disease and/or effusion, lack of calcification and high uptake on positron emission tomography computerised tomography. A 68-year-old woman presented with a 3-month history of cough. Imaging studies showed a right upper lobe mass with internal foci of calcification, endobronchial extension, and low fluorodeoxyglucose avidity on positron emission tomography computerised tomography, leading to an initial diagnosis of carcinoid tumor. However, histologic specimens suggested an unexpected diagnosis of aggressive synovial sarcoma, and the case was referred to the sarcoma MDT. Metastatic synovial sarcoma was ruled out, and radical surgical excision of the lesion was performed. This article highlights the multiple atypical features of primary pleuropulmonary synovial sarcoma as seen in this case and reviews imaging findings described in the literature. Radiologists should be aware of this unusual yet aggressive type of sarcoma. PMID- 27257448 TI - Pancreatic lipoma with a solid nodule mimicking invasion from adjoining intraductal papillary mucinous neoplasm. AB - A 74-year-old man was referred to our hospital for a mass in the pancreatic head found during screening chest computed tomography. Contrast computed tomography showed a 5-cm multicystic mass with an irregular border containing a solid component showing contrast enhancement. Caudal to this mass, a 5-cm solid mass of fat density with a nodular soft-tissue component was found. Cytology of the aspirated pancreatic fluid revealed malignant cells, and surgery was performed for suspected intraductal papillary mucinous carcinoma. Pathologic analysis of the resected specimen revealed a collision tumor of intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia and pancreatic lipoma. The soft-tissue component within the lipoma was a nodule consisting of pancreatic tissue with inflammatory infiltration and hyalinization and was not associated with IPMN invasion. PMID- 27257449 TI - Disseminated cat-scratch disease in an adult with selective IgA deficiency. AB - A 51-year-old man with history of undiagnosed pulmonary nodules 4 years prior, presented with right-sided chest pain. Acute cardiac workup was negative, and a chest computed tomography examination demonstrated marked improvement in bilateral pulmonary nodules. A concordant abdominal computed tomography examination showed new subcentimeter hypodense lesions throughout the liver and spleen, mild progressive abdominopelvic lymphadenopathy, and new small lytic lesions of T11 and L4 vertebrae. A positron emission tomography examination demonstrated hypermetabolic activity of these abdominopelvic lesions suggesting metastatic disease. Extensive laboratory workup was negative, aside from IgA deficiency. Eventually, biopsy of a hepatic lesion was performed and compatible with Bartonella species. An elevated Bartonella IgG titer was noted, consistent with Bartonella Hensalae infection, or "cat-scratch disease." Radiographic findings showed marked improvement after clinically appropriate antibiotic therapy. PMID- 27257450 TI - Clinical case report: Sclerosing hemangioma of the liver, a rare but great mimicker. AB - Atypical hemangioma (including sclerosing and/or hyalinizing hemangioma) of the liver is a rare variant of hepatic hemangioma, which is the most common benign hepatic tumor. Atypical hemangioma can be indistinguishable from malignancy, primary, or metastatic, based on imaging characteristics. We describe a case of a 70-year-old man with weight loss, occasional bloody stool, change in caliber of stool, and laboratory abnormalities who was found to have multiple hepatic lesions concerning for metastases. We demonstrate that knowledge of the appearance of atypical hemangioma and its inclusion in the differential diagnosis of hepatic lesions can alter patient management and be important to consider before invasive therapies are planned. PMID- 27257451 TI - Transient washout of hepatic hemangiomas: Potential pitfall mimicking malignancy. AB - Hemangiomas are the most common tumor of the liver and distinguishing them from malignancy is important. This is a report of 3 hemangiomas in 2 patients that exhibit transient washout of gadoxetate disodium (Eovist), relative to blood pool and liver parenchyma, a characteristic that is used to diagnose hepatocellular carcinoma in at-risk patients. It is important to recognize that high-flow hemangiomas can exhibit transient washout when using a small volume of injected contrast agent. This finding is unlikely to be present on CT examinations because of the larger volume of contrast administered. PMID- 27257452 TI - Massive gas gangrene secondary to occult colon carcinoma. AB - Gas gangrene is a rare but often fatal soft-tissue infection. Because it is uncommon and the classic symptom of crepitus does not appear until the infection is advanced, prompt diagnosis requires a high index of suspicion. We present a case report of a middle-aged man who presented with acute onset lower-extremity pain that was initially thought to be due to deep vein thrombosis. After undergoing workup for pulmonary embolism, he was found to have massive gas gangrene of the lower extremity secondary to an occult colon adenocarcinoma and died within hours of presentation from multisystem organ failure. PMID- 27257453 TI - Computed tomography demonstration of cholecystogastric fistula. AB - Cholecystogastric fistula is a rare complication of chronic cholecystitis or long standing cholelithiasis. It results from the gradual erosion of the approximated, chronically inflamed wall of the gall bladder and stomach with fistulous tract formation. The present case describes the direct visualization of a cholecystogastric fistula by computed tomography in a patient without prior biliary system complaints. PMID- 27257454 TI - Renal squamous cell carcinoma mimicking xanthogranulomatous pyelonephritis: Case report and review of literature. AB - Primary renal squamous cell carcinoma (SCC) is a rare primary malignancy of the kidney. Diagnosis is usually delayed because of its lack of characteristic clinical and imaging features and inherent aggressive nature. We present a case of primary renal SCC in a 66-year-old woman with bilateral renal calculi and a complex right lower pole renal mass. The diagnosis of primary renal SCC was established based on the histopathology after right nephrectomy. PMID- 27257455 TI - Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma. AB - We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient. PMID- 27257456 TI - Control of massive hemoptysis via a "back-door" approach through the pulmonary artery. AB - Bronchial artery embolization is an effective nonsurgical therapy for massive hemoptysis. Routine selection of the bronchial arteries from the aorta usually enables the interventionalist full interrogation and embolization of the culprit vascular abnormality. In problematic cases where bronchial artery access is difficult, a systemic-to-pulmonary arterial shunt can be exploited as a retrograde means of vascular intervention. A case is presented where inaccessibility of a tortuous left bronchial artery was circumvented by accessing the left pulmonary artery, leading to successful embolization and control of hemoptysis. PMID- 27257457 TI - Atraumatic splenic rupture precipitated by splenic vein thrombosis. AB - We present the case of a 59-year-old man with atraumatic splenic rupture because of splenic vein thrombosis who was successfully treated with splenic artery embolization. PMID- 27257458 TI - Acute tumor lysis syndrome after proximal splenic artery embolization. AB - Preoperative splenic artery embolization for massive splenomegaly has been shown to reduce intraoperative hemorrhage during splenectomy. We describe a case of tumor lysis syndrome after proximal splenic artery embolization in a patient with advanced mantle cell lymphoma and splenic involvement. The patient presented initially with hyperkalemia two days after embolization that worsened during splenectomy. He was stabilized, but developed laboratory tumor lysis syndrome with renal failure and expired. High clinical suspicion of tumor lysis syndrome in this setting is advised. Treatment must be started early to avoid serious renal injury and death. Lastly, same day splenectomy and embolization should be considered to decrease the likelihood of developing tumor lysis syndrome. PMID- 27257459 TI - Massive exophytic malignant peripheral nerve sheath tumor. AB - We present a case of a solitary neurofibroma involving the right posterior shoulder of a 69-year-old man with degeneration into a massive, malignant peripheral nerve sheath tumor measuring more than 3 times the average reported size. The radiographic, magnetic resonance imaging, and computed tomographic features are compared with the gross appearance and pathology. PMID- 27257460 TI - Synovial cutaneous fistula complicating a reverse total shoulder arthroplasty. AB - Reverse total shoulder arthroplasty is becoming a common form of shoulder arthroplasty that is often performed in the setting of rotator cuff pathology. Infection is a rare complication but is more common in reverse total shoulder arthroplasty than in hemiarthroplasty or anatomic total shoulder arthroplasty. We present the case of a 69-year-old patient with a reverse total shoulder arthroplasty who presented with purulent drainage from the skin of his anterior shoulder. Computed tomography arthrogram confirmed the presence of a synovial cutaneous fistula. Synovial cutaneous fistula is a rare variant of periprosthetic infection that, to our knowledge, has not been described previously in the setting of a reverse total shoulder arthroplasty. Computed tomography arthrogram proved to be a reliable method for confirming the diagnosis and was used for operative planning to remove the hardware. PMID- 27257461 TI - A rare case of dermatofibrosarcoma protuberans of the forefoot. AB - Dermatofibrosarcoma protuberans is an extremely rare, potentially malignant tumor type that usually presents on the trunk or proximal extremities. The clinical presentation includes a gradually enlarging painless plaque-like or nodular lesion of the skin with surrounding red to blue discoloration. The diagnosis is based on clinical presentation, computed tomography or magnetic resonance imaging, and biopsy with histologic analysis. An early and timely diagnosis improves chances of complete surgical resection thus improving prognosis. Herein, we present a rare case of dermatofibrosarcoma protuberans with the hopes that its addition to the literature will aid in the earlier recognition of future patients and help prevent this potentially curable disease from becoming deadly. PMID- 27257462 TI - Experience with a triple-lumen catheter for autologous stem-cell transplantation. AB - We relate our experience with the Cook (Cook Medial Inc., Bloomington, IN, USA), triple-lumen hyperalimentation (HAS) catheter for treatment related to autologous stem-cell transplant. Nineteen HAS catheters were implanted in the right jugular vein, and tunneled to the right anterior chest wall, under imaging guidance. Retrospectively, we reviewed each catheter. Three patient's experienced "ballooning" of the middle (white) lumen of the HAS catheter during routine use. We assessed, time in situ, follow-up imaging, chemotherapy regimen, possibility of systemic or device infection, tissue pathology of the patient's malignancy, and other factors to attempt to determine if there were any associations that could explain the catheter lumen failure. After this pilot study of the HAS catheter in these 19 patients, we discontinued use of this device at our facility due to mechanical problems of ballooned and obstructed middle lumens. There was no obvious cause, or association, detected to explain the ballooning identified. PMID- 27257463 TI - Nodular fasciitis mimicking recurrent lymphoma on positron emission tomography computed tomography. AB - 20 year old female with no prior medical history presents with diffuse cervical lymphadenopathy. CT and subsequent positron emission tomography-computed tomography (PET/CT) demonstrated diffuse lymphatomous involvement of multiple lymph nodes in the neck, mediastinum, and retroperitoneum. The patient underwent ABVD therapy which resulted in the lymphoma being in remission for 2 years. The patient had a repeat PET/CT done after 2 years due to complaints of recurrent lymphadenopathy. The PET/CT revealed a new hypermetabolic focus by the right femur. MRI demonstrated an enhancing nodule in that region which raised suspicion for possible site of lymphoma recurrence. Percutaneous biopsy showed nodular fasciitis. PMID- 27257464 TI - Persistent bronchography in a newborn with esophageal atresia. AB - Esophageal atresia (EA) with tracheoesophageal fistula occurs in about 1:2,500 births. We report a case of persistent bronchography in a newborn with EA and distal tracheoesophageal fistula. A large amount of barium sulfate was injected for mistake by a tube directly in the right bronchus to evaluate the patency of the esophagus. The infant showed signs of respiratory distress; he was intubated and transported at children's Hospital Santobono Pausilipon. Here, it was performed a chest X-ray that confirmed the opacification of the right bronchial tree, and it was suspected an EA type 3b. The literature recommends that: evaluation of the patency of the esophagus, with an iodinate contrast medium, should be done in a pediatric specialized center for high risk of lung aspiration. PMID- 27257465 TI - Prenatal sonographic diagnosis of limb-body wall complex: case series of a rare congenital anomaly. AB - Three case reports of a rare congenital anomaly "limb-body wall complex" also known as "body stalk syndrome" are presented with prenatal ultrasonographic diagnostic features, immediate after delivery evaluation, and histopathologic analysis. PMID- 27257466 TI - Testicular hemangioma mimicking a malignant neoplasm. AB - A 34-year-old man who presented with right scrotal pain, and who on subsequent ultrasound examination, was found to have an intratesticular hypoechoic mass. Based on the ultrasound appearance of this mass, a malignant germ cell tumor was thought to be the most likely diagnosis. Preoperative serum tumor markers, including lactate dehydrogenase, alpha-1-fetoprotein, and beta-human chorionic gonadotropin, were negative. Computed tomography imaging of the chest, the abdomen, and the pelvis revealed no evidence of metastasis. The patient underwent right orchiectomy, and final pathology demonstrated a benign hemangioma. PMID- 27257467 TI - CO Adsorption on Reconstructed Ir(100) Surfaces from UHV to mbar Pressure: A LEED, TPD, and PM-IRAS Study. AB - Clean and stable surface modifications of an iridium (100) single crystal, i.e., the (1 * 1) phase, the (5 * 1) reconstruction, and the oxygen-terminated (2 * 1) O surface, were prepared and characterized by low energy electron diffraction (LEED), temperature-programmed desorption (TPD), infrared reflection absorption spectroscopy (IRAS) and polarization modulation IRAS (PM-IRAS). The adsorption of CO in UHV and at elevated (mbar) pressure/temperature was followed both ex situ and in situ on all three surface modifications, with a focus on mbar pressures of CO. The Ir(1 * 1) surface exhibited c(4 * 2)/c(2 * 2) and c(6 * 2) CO structures under low pressure conditions, and remained stable up to 100 mbar and 700 K. For the (2 * 1)-O reconstruction CO adsorption induced a structural change from (2 * 1)-O to (1 * 1), as confirmed by LEED, TPD, and IR. For Ir (2 * 1)-O TPD indicated that CO reacted with surface oxygen forming CO2. The (5 * 1) reconstruction featured a reversible and dynamic behavior upon CO adsorption, with a local lifting of the reconstruction to (1 * 1). After CO desorption, the (5 * 1) structure was restored. All three reconstructions exhibited CO adsorption with on-top geometry, as evidenced by IR. With increasing CO exposure the resonances shifted to higher wavenumber, due to adsorbate-adsorbate and adsorbate substrate interactions. The largest wavenumber shift (from 2057 to 2100 cm-1) was observed for Ir(5 * 1) upon CO dosing from 1 L to 100 mbar. PMID- 27257469 TI - Benzocaine-Induced Cyanosis. PMID- 27257468 TI - Interparental Violence and the Mediating Role of Parental Availability in Children's Trauma Related Symptoms. AB - This cross-sectional study examined the hypothesis that parental psychopathology in Interparental Violence (IPV) families crosses over to children, because parental psychopathology spills over to parental functioning. In a high-risk sample of IPV exposed families, we tested whether parental psychopathology spills over to parental availability, which, in turn, shows a crossover effect to children's trauma-related symptoms. The study population consisted of 78 IPV exposed children (4-12 years), and their 65 custodial parents referred to outpatient Children's Trauma Centers in the Netherlands for intervention. Consistent with our hypotheses, parental psychopathology was negatively related to parental availability, suggesting a spillover effect. Although parental psychopathology was not associated with children's trauma-related symptoms directly, we found evidence for the predicted indirect, crossover effects. We found an indirect crossover effect from parental psychopathology to children's trauma-related anxiety, depression, and anger, through the spillover effect of parental availability. Clinical implications for treatment and study limitations are discussed. PMID- 27257470 TI - A Graph Based Framework to Model Virus Integration Sites. AB - With next generation sequencing thousands of virus and viral vector integration genome targets are now under investigation to uncover specific integration preferences and to define clusters of integration, termed common integration sites (CIS), that may allow to assess gene therapy safety or to detect disease related genomic features such as oncogenes. Here, we addressed the challenge to: 1) define the notion of CIS on graph models, 2) demonstrate that the structure of CIS enters in the category of scale-free networks and 3) show that our network approach analyzes CIS dynamically in an integrated systems biology framework using the Retroviral Transposon Tagged Cancer Gene Database (RTCGD) as a testing dataset. PMID- 27257471 TI - Common integration sites of published datasets identified using a graph-based framework. AB - With next-generation sequencing, the genomic data available for the characterization of integration sites (IS) has dramatically increased. At present, in a single experiment, several thousand viral integration genome targets can be investigated to define genomic hot spots. In a previous article, we renovated a formal CIS analysis based on a rigid fixed window demarcation into a more stretchy definition grounded on graphs. Here, we present a selection of supporting data related to the graph-based framework (GBF) from our previous article, in which a collection of common integration sites (CIS) was identified on six published datasets. In this work, we will focus on two datasets, ISRTCGD and ISHIV, which have been previously discussed. Moreover, we show in more detail the workflow design that originates the datasets. PMID- 27257472 TI - Characterization of osteoarthritic human knees indicates potential sex differences. AB - BACKGROUND: The prevalence of osteoarthritis is higher in women than in men in every age group, and overall prevalence increases with advancing age. Sex specific differences in the properties of osteoarthritic joint tissues may permit the development of sex-specific therapies. Sex hormones regulate cartilage and bone development and homeostasis in a sex-dependent manner. Recent in vitro studies show that the vitamin D3 metabolite 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] also has sex-specific effects on musculoskeletal cells, suggesting that vitamin D3 metabolites may play a role in osteoarthritis-related sex-specific differences. The purpose of this study was to determine if sex specific differences exist in synovial fluid and knee tissues isolated from male and female patients with severe knee osteoarthritis. We determined the presence of vitamin D3 metabolites, inflammatory cytokines, growth factors, and matrix metalloproteinases (MMPs) in synovial fluid and assessed responses of articular chondrocytes and subchondral osteoblasts to 17beta-estradiol, dihydrotestosterone, and 1alpha,25(OH)2D3. METHODS: Samples from knee joints of 10 Caucasian male and 10 Caucasian female patients with advanced osteoarthritis aged 65 to 75 years were obtained from total knee arthroplasty. Vitamin D metabolites, cytokines, MMPs, and growth factors in the synovial fluid were measured. Primary cultures of chondrocytes were isolated from fibrillated articular cartilage adjacent to osteoarthritis lesions and minimally affected cartilage distal to the lesion. Osteoblasts were isolated from the subchondral bone. Expression of receptors for 17beta-estradiol and 1alpha,25(OH)2D3 was assessed by real-time PCR. Chondrocytes and osteoblasts were treated with 10(-8) M 17beta-estradiol, dihydrotestosterone, or 1alpha,25(OH)2D3 and effects on gene expression and protein synthesis determined. RESULTS: Histology of the articular cartilage confirmed advanced osteoarthritis. Sex differences were found in synovial fluid levels of vitamin D metabolites, cytokines, and metalloproteinases as well as in the cellular expression of receptors for 17beta-estradiol and 1alpha,25(OH)2D3. Male cells were more responsive to 1alpha,25(OH)2D3 and dihydrotestosterone, whereas 17beta-estradiol-affected female cells. CONCLUSIONS: These results demonstrate that there are underlying sex differences in knee tissues affected by osteoarthritis. Our findings do not address osteoarthritis etiology but have implications for different prevention methods and treatments for men and women. Further research is needed to better understand these sex based differences. PMID- 27257473 TI - Gene changes may minimize masculinizing and defeminizing influences of exposure to male cotwins in female callitrichine primates. AB - BACKGROUND: Sexual differentiation in female mammals can be altered by the proximity of male littermates in utero, a phenomenon known as the intrauterine position effect (IUP). Among simian primates, callitrichines (marmosets and tamarins) are likely candidates for IUP, since they exhibit obligate dizygotic twinning and fetuses share extensive vascularization in utero. In this paper, we determined whether female reproductive parameters are altered by gestating with a male twin and evaluated changes in genes associated with anti-Mullerian and steroid hormones in twinning callitrichine primates. METHODS: We assessed the impact of gestation with male cotwins on reproductive performance and survivorship in female marmosets (Callithrix) and lion tamarins (Leontopithecus), contrasting measures for females gestated with one or more littermates (M+) or no male littermates (0M). We compared targeted coding regions for genes involved in steroidal and anti-Mullerian hormone mediation of sexual differentiation for representatives of twinning callitrichines (Callithrix, Saguinus, and Leontopithecus) with closely related New World primates that produce single births (Saimiri and Callimico). RESULTS: IUP effects in females were absent in female callitrichine primates: age at first ovulation, average litter size, and the proportion of stillborn infants, and lifetime survivorship did not differ between M+ and 0M females. We documented multiple nonsynonymous substitutions in genes associated with steroid synthesis, transport, and cellular action (SRD5A2, CYP19A1, SHBG, and AR) and with anti-Mullerian hormone (AMH and AMHR2) in callitrichines. In the only callitrichine to produce single infants (Callimico), two genes contained nonsynonymous substitutions relative to twinning callitrichines (CYP19A1 and AMRHR2); these substitutions were identical with nontwinning Saimiri and humans, suggesting a reversion to an ancestral sequence. CONCLUSIONS: In spite of a shared placental vasculature with opposite-sex twins throughout embryonic and fetal development, female callitrichine primates gestated with a male cotwin exhibit no decrement in reproductive performance relative to females gestated with female cotwins. Hence, IUP effects on female reproduction in callitrichines are modest. We have identified mutations in candidate genes relevant for steroid hormone signaling and metabolism, and especially in AMH-related genes, that are likely to alter protein structure and function in the callitrichines. These mutations may confer protection for females from the masculinizing and defeminizing influences of gestating with a male cotwin. PMID- 27257475 TI - Nutritional adequacy of a cows' milk exclusion diet in infancy. AB - BACKGROUND: Infants with suspected cows' milk allergy are required to follow a strict milk exclusion diet which may lead to nutritional deficiencies, especially if not supervised by a healthcare professional. The aim of this study was to assess the nutritional adequacy of a cows' milk exclusion diet in a group of UK infants over a period of 6 months. METHODS: Participants in this study are a subgroup of the Prevalence of Infant Food Allergy study, a prospective food allergy birth cohort study from the South of England. Each infant consuming a milk free diet, following advice from a specialist allergy dietitian, was matched to two control infants who were consuming an unrestricted diet, forming a nested matched case-control study. Detailed food diaries completed prospectively for 1 week per month over a 5 month period, were coded and analysed according to a standard protocol. RESULTS: The diets of 39 infants (13 milk-free and 26 controls) were assessed. Mean age at diet commencement was 14 weeks. Two of the eleven infants started on an extensively hydrolysed formula did not tolerate it and required an amino acid formula for symptom resolution. All infants had mean intakes in excess of the estimated average requirement for energy and the recommended nutrient intake (RNI) for protein, calcium, iron, selenium, zinc, vitamins A, C and E. Vitamin D intake was in excess of the RNI at all time points, except at 44 weeks of age. Across the study period, selenium intake was higher for infants consuming a milk free diet whilst vitamin C intake was higher for infants consuming an unrestricted diet. Differences were found between the two groups for protein, calcium, iron and vitamin E intakes at differing time points. CONCLUSION: This study demonstrated that although infants consuming a milk-free diet have a nutritional intake that is significantly different to matched controls who are eating an unrestricted diet, this difference is not constant and it is not seen for all nutrients. Further research in infants without dietetic input is needed to explore the nutritional implications of unsupervised cows' milk exclusion diets. PMID- 27257474 TI - Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy. AB - BACKGROUND: Secondary dystroglycanopathies are a subset of muscular dystrophy caused by abnormal glycosylation of alpha-dystroglycan (alphaDG). Loss of alphaDG functional glycosylation prevents it from binding to laminin and other extracellular matrix receptors, causing muscular dystrophy. Mutations in a number of genes, including FKTN (fukutin), disrupt alphaDG glycosylation. METHODS: We analyzed conditional Fktn knockout (Fktn KO) muscle for levels of mTOR signaling pathway proteins by Western blot. Two cohorts of Myf5-cre/Fktn KO mice were treated with the mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) for 4 weeks and evaluated for changes in functional and histopathological features. RESULTS: Muscle from 17- to 25-week-old fukutin-deficient mice has activated mTOR signaling. However, in tamoxifen-inducible Fktn KO mice, factors related to Akt/mTOR signaling were unchanged before the onset of dystrophic pathology, suggesting that Akt/mTOR signaling pathway abnormalities occur after the onset of disease pathology and are not causative in early dystroglycanopathy development. To determine any pharmacological benefit of targeting mTOR signaling, we administered RAPA daily for 4 weeks to Myf5/Fktn KO mice to inhibit mTORC1. RAPA treatment reduced fibrosis, inflammation, activity-induced damage, and central nucleation, and increased muscle fiber size in Myf5/Fktn KO mice compared to controls. RAPA-treated KO mice also produced significantly higher torque at the conclusion of dosing. CONCLUSIONS: These findings validate a misregulation of mTOR signaling in dystrophic dystroglycanopathy skeletal muscle and suggest that such signaling molecules may be relevant targets to delay and/or reduce disease burden in dystrophic patients. PMID- 27257476 TI - Psychological factors in exceptional, extreme and torturous environments. AB - Our cognitive system has adapted to support goal-directed behaviour within a normal environment. An abnormal environment is one to which we are not optimally adapted but can accommodate through the development of coping strategies. These abnormal environments can be 'exceptional', e.g., polar base, space station, submarine, prison, intensive care unit, isolation ward etc.; 'extreme', marked by more intense environmental stimuli and a real or perceived lack of control over the situation, e.g., surviving at sea in a life-raft, harsh prison camp etc.; or 'tortuous', when specific environmental stimuli are used deliberately against a person in an attempt to undermine his will or resistance. The main factors in an abnormal environment are: psychological (isolation, sensory deprivation, sensory overload, sleep deprivation, temporal disorientation); psychophysiological (thermal, stress positions), and psychosocial (cultural humiliation, sexual degradation). Each single factor may not be considered tortuous, however, if deliberately structured into a systemic cluster may constitute torture under legal definition. The individual experience of extremis can be pathogenic or salutogenic and attempts are being made to capitalise on these positive experiences whilst ameliorating the more negative aspects of living in an abnormal environment. PMID- 27257477 TI - The case for genome-wide association studies of bone acquisition in paediatric and adolescent populations. AB - Peak bone mass, the maximum amount of bone accrued at the end of the growth period, is an important predictor of future risk of osteoporosis and fracture. Hence, the contribution of genetic factors influencing bone accrual is of considerable interest to the osteoporosis research community. In this article, we review evidence that genetic factors play an important role in bone growth, describe the genetic loci implicated so far and briefly discuss lessons learned from the application of genome-wide association studies. Moreover, we attempt to make the case for genetic investigations of bone mineral density in paediatric and young adult populations, describing their potential to increase our knowledge of the process of bone metabolism throughout the life course, and in turn, identify novel targets for the pharmacological treatment of osteoporosis. PMID- 27257478 TI - Meta-analysis of risk factors for Parkinson's disease dementia. AB - BACKGROUND: Parkinson's disease (PD) is a common heterogeneous neurodegenerative disorder in elder population. Parkinson's disease dementia (PDD) is one of the most common non-motor manifestations in PD patients. No comprehensive review has been conducted to assess risk factors for PDD. METHODS: A systemic search for studies on PDD risk factors was performed. Cohort and case-control studies that clearly defined PDD and presented relevant data were included. The data were analyzed to generate a pooled effect size and 95 % confidence interval (CI). Publication bias was assessed using the Egger's test and the Begg's test. RESULTS: A systematic search was conducted and yielded 5195 articles. After screening, 25 studies were included in the current analysis. Development of PDD was positively associated with age (odds ratio [OR] 1.07, 95 % CI 1.03-1.13), male (OR 1.33, 95 % CI 1.08-1.64), higher Unified Parkinson's Disease Rating Scale (UPDRS) part III scores (relative risk [RR] 1.04, 95 % CI 1.01-1.07), hallucination (OR 2.47, 95 % CI 1.36-4.47), REM sleep behavior disorder (RBD) (OR 8.38, 95 % CI 3.87-18.08), smoking (ever vs. never) (RR 1.93, 95 % CI 1.15-3.26) and hypertension (OR 1.57, 95 % CI 1.11-2.22). An inverse association was found between education (RR 0.94, 95 % CI 0.91-0.98) and PDD. Other reported factors, including age of onset, disease duration of PD, Hoehn and Yahr stage and diabetes mellitus were not significantly associated with PDD. CONCLUSIONS: Advanced age, male, higher UPDRS III scores, hallucination, RBD, smoking and hypertension increase the risk of PDD, whereas higher education is a protective factor for PDD. PMID- 27257480 TI - Emergency surgical treatment of complicated acute pancreatitis after kidney transplantation with acute rejection: Case report and literature review. AB - INTRODUCTION: Acute pancreatitis is a rare but frequently fatal complication in patients following kidney transplantation. The first case of acute pancreatitis in patients following a kidney transplant was described by Starzl in 1964. The incidence of acute pancreatitis is stated at between 1 and 5%. The mortality rate amongst these patients reaches as high as 50-100%. PRESENTATION OF CASE: Here we present a case of acute pancreatic abscess in a caucasian female - shortly following a kidney transplant complicated by the development of acute rejection, in which immunosuppressant therapy is a potential etiological agent. Emergency surgical treatment was indicated, which included drainage of the abscesses irrigation of the abdominal cavity. Immunosuppressive medication was considered a possible etiological factor, and as a result administration of tacrolimus and mycophenolate mofetil was discontinued. This was successful and three months later, diagnostic rebiopsy of the graft was performed without signs of rejection. DISCUSSION: The etiology of this illness is multifactorial. The clinical manifestation of acute pancreatitis in patients following kidney transplantation is the same as in the remainder of the population. However, in patients following transplantation with long-term immunosuppression, it usually manifests a more rapid development and a more severe, frequently fatal course. CONCLUSIONS: With regard to the patient's comorbidities, early surgical therapy was indicated - drainage and closed lavage and immunosuppressive medication as a suspected tobe ethiological factor was discontinued. This course of treatment led to a complete recovery with preservation of good function of the cadaverous kidney. PMID- 27257479 TI - Empirical evaluation of a virtual laboratory approach to teach lactate dehydrogenase enzyme kinetics. AB - BACKGROUND: Personalised instruction is increasingly recognised as crucial for efficacious learning today. Our seminal work delineates and elaborates on the principles, development and implementation of a specially-designed adaptive, virtual laboratory. AIMS: We strived to teach laboratory skills associated with lactate dehydrogenase (LDH) enzyme kinetics to 2nd-year biochemistry students using our adaptive learning platform. Pertinent specific aims were to:(1)design/implement a web-based lesson to teach lactate dehydrogenase(LDH) enzyme kinetics to 2nd-year biochemistry students(2)determine its efficacious in improving students' comprehension of enzyme kinetics(3)assess their perception of its usefulness/manageability(vLab versus Conventional Tutorial). METHODS: Our tools were designed using HTML5 technology. We hosted the program on an adaptive e-learning platform (AeLP). Provisions were made to interactively impart informed laboratory skills associated with measuring LDH enzyme kinetics. A series of e learning methods were created. Tutorials were generated for interactive teaching and assessment. RESULTS: The learning outcomes herein were on par with that from a conventional classroom tutorial. Student feedback showed that the majority of students found the vLab learning experience "valuable"; and the vLab format/interface "well-designed". However, there were a few technical issues with the 1st roll-out of the platform. CONCLUSIONS: Our pioneering effort resulted in productive learning with the vLab, with parity with that from a conventional tutorial. Our contingent discussion emphasises not only the cornerstone advantages, but also the shortcomings of the AeLP method utilised. We conclude with an astute analysis of possible extensions and applications of our methodology. PMID- 27257481 TI - Advanced colorectal cancer resulting in acute bowel obstruction during pregnancy; a case report. AB - INTRODUCTION: Abdominal pain is frequently found in the pregnant population; however life-threatening pathology such as colorectal cancer does occur rarely. As such, intestinal obstructions are usually attributed to pregnancy-related issues. We present the case of a young woman with an acute bowel obstruction caused by advanced colorectal carcinoma. PRESENTATION OF CASE: A 34-year old pregnant woman was referred to our emergency department with complaints of severe upper abdominal pain. Initial investigations did not show abdominal pathology and conservative treatment for obstipation was commenced. However, complaints persisted and a near blowout of the colon was diagnosed, prompting a caesarean section and diagnostic laparotomy. An obstructing tumour was found and a left sided hemi-colectomy was performed. Unfortunately, skeletal, lymphatic and additional hepatogenic metastasis were discovered during chemotherapy and treatment was discontinued. DISCUSSION AND CONCLUSION: The mainstay of abdominal complaints during pregnancy can be attributed to normal physiological alterations associated with gravidity. Nonetheless serious pathology should be considered, especially when conservative treatment fails. On this note, diagnostic imaging during pregnancy should be used promptly upon suspicion of serious abdominal pathology. PMID- 27257482 TI - A multicenter review of epidemiology and management of varicose veins for national guidance. AB - BACKGROUND: Varicose vein is a common surgical problems in India. This study was done to assess the clinico-epidemiological profile, risk factors and management practices in varicose veins. MATERIALS AND METHODS: Medical records of 170 varicose vein cases admitted in tertiary care hospitals in Mangalore between May 2011 to April 2014 were reviewed retrospectively. RESULTS: Majority of cases 53(31.2%) were of the age group 41-50 years. Majority were males 127(74.7%) and majority were unskilled workers 101(59.4%). Superficial veins were involved in 123(72.4%) cases. Perforator followed by great saphenous vein were most frequently involved. Veins on the left side were more involved than on the right. Common symptoms at the time of presentation was ulceration 98(57.6%) followed by pain in the legs 96(56.5%). Ulceration was seen significantly more among females (p = 0.027) and among house wives (p = 0.004). Complications like eczema 46(27.1%), non-healing ulcers 21(12.3%) and deep vein thrombosis 10(5.9%) were reported among cases. Eczema was present significantly more among elderly patients aged above 60 years (p = 0.019). Risk factors like prolonged standing was observed in 86(50.6%) cases. This history was significantly seen among males (p = 0.001) and among those involved in unskilled occupations (p < 0.001). Recurrence of varicose vein was reported in 23(13.5%) cases. It was associated with patients of the age group 21-30 years (p = 0.021). Doppler ultrasound was the most common 120(70.6%) investigation done. Micronized purified flavonoid fraction was used in management in 15(8.8%) cases. Conservative management methods like limb elevation 50(29.4%) and compression stocking 36(21.2%) was advised to patients. Saphenous vein stripping was the most common surgical procedure 40(23.5%) performed. CONCLUSION: The high risk groups identified in this study need to be made aware of risk of developing varicose veins. Use of compression stocking at work place added with newer procedure in management could help in betterment in their quality of life. PMID- 27257483 TI - Hepatic arterial and portal venous complications after adult and pediatric living donor liver transplantation, risk factors, management and outcome (A retrospective cohort study). AB - OBJECTIVES: Hepatic arterial (HA) and portal venous (PV) complications of recipients after living donor liver transplantation(LDLT) result in patient loss. The aim of this study was to analyze these complications. METHODS: We retrospectively analyzed HA and/or PV complications in 213 of 222 recipients underwent LDLT in our centre. The overall male/female and adult/pediatric ratios were 183/30 and 186/27 respectively. RESULTS: The overall incidence of HA and/or PV complications was 19.7% (n = 42), while adult and pediatric complications were 18.3% (n = 39) and 1.4% (n = 3) respectively. However early (<1month) and late (>1month) complications were 9.4% (n = 20) and 10.3% (n = 22) respectively. Individually HA problems (HA stenosis, HA thrombosis, injury and arterial steal syndrome) 15% (n = 32), PV problems (PV thrombosis and PV stenosis) 2.8% (n = 6) and simultaneous HA and PV problems 1.9% (n = 4). 40/42 of complications were managed by angiography (n = 18), surgery (n = 10) or medically (Anticoagulant and/or thrombolytic) (n = 12) where successful treatment occurred in 18 patients. 13/42 (31%) of patients died as a direct result of these complications. Preoperative PVT was significant predictor of these complications in univariate analysis. The 6-month, 1-, 3-, 5- 7- and 10-year survival rates in patients were 65.3%, 61.5%, 55.9%, 55.4%, 54.5% and 54.5% respectively. CONCLUSION: HA and/or PV complications specially early ones lead to significant poor outcome after LDLT, so proper dealing with the risk factors like pre LT PVT (I.e. More intensive anticoagulation therapy) and the effective management of these complications are mandatory for improving outcome. PMID- 27257484 TI - Intestinal blood flow assessment by indocyanine green fluorescence imaging in a patient with the incarcerated umbilical hernia: Report of a case. AB - After reduction of the incarceration during surgery for incarcerated hernia, intestinal blood flow (IBF) and the need for bowel resection must be evaluated. We report the case of a patient with incarcerated umbilical hernia in whom the bowel was preserved after evaluating IBF using indocyanine green (ICG) fluorescence. A woman in her 40s with a chief complaint of abdominal pain visited our hospital, was diagnosed with incarcerated umbilical hernia and underwent surgery. Laparotomy was performed to reduce bowel incarceration. After reducing the incarceration, IBF was observed using ICG fluorescence detected using a brightfield full-color fluorescence camera. The small bowel that had been incarcerated showed deep-red discoloration on gross evaluation, but intravenous injection of ICG revealed uniform fluorescence of the mesentery and bowel wall. This indicated an absence of irreversible ischemic changes of the bowel, so no resection was performed. The patient showed a good postoperative course, including resumption of eating on day 4 and discharge on day 11. In surgery for incarcerated hernia, ICG fluorescence may offer a useful method to evaluate IBF after reducing the incarceration. This case implied that PINPOINT could be used in open conventional surgery. PMID- 27257485 TI - Detection of benign hilar bile duct stenoses - A retrospective analysis in 250 patients with suspicion of Klatskin tumour. AB - INTRODUCTION: The aim of this study was to identify clinical, laboratory and radiological parameters to distinguish benign from malignant stenoses of the proximal bile duct. METHODS: Between 1997 and 2011, 250 patients were referred to our clinic with hilar bile duct stenoses suspicious for Klatskin tumour. Medical histories, clinical data, pre-interventional laboratory tests, imaging findings, as well as therapeutic approach and patient outcome were compared to final histological results. All data were retrieved from our prospectively maintained database and analysed retrospectively. RESULTS: We found benign bile duct lesions in 34 patients (13.6%). Among the entire study population, uni- and multivariate analyses of 18 clinicopathological parameters revealed that patient age, serum alkaline phosphatase, tumour marker CA19-9 and presence of tumour mass in computed tomography were independent predictors for malignant biliary stenoses (p < 0.05). Receiver operator characteristic curve showed that a CA19-9 serum level of 61.2 U/ml or more has a sensitivity, specificity and diagnostic accuracy for predicting the malignant nature of the hilar biliary stenoses of 74.6%, 80.0% and 83.5%, respectively. Surgical resection could be avoided by preoperative work-up and surgical exploration in 10 out of 34 patients with benign lesions. Rates of major liver resections performed were 66.7% in the benign lesion group and 90.7% in the Klatskin tumour group. CONCLUSION: Despite improvements of preoperative diagnostics, it remains difficult to differentiate between benign and malignant hilar bile duct stenosis. Even explorative laparotomy was not able to safely exclude Klatskin tumour in all cases and therefore major liver resection was inevitable. PMID- 27257486 TI - Noncontiguous finished genome sequence and description of Bacillus andreraoultii strain SIT1(T) sp. nov. AB - Bacillus andreraoultii strain SIT1(T) (= CSUR P1162 = DSM 29078) is the type strain of B. andreraoultii sp. nov. This bacterium was isolated from the stool of a 2-year-old Nigerian boy with a severe form of kwashiorkor. Bacillus andreraoultii is an aerobic, Gram-positive rod. We describe here the features of this bacterium, together with the complete genome sequencing and annotation. The 4 092 130 bp long genome contains 3718 protein-coding and 116 RNA genes. PMID- 27257487 TI - Noncontiguous finished genome sequence and description of Planococcus massiliensis sp. nov., a moderately halophilic bacterium isolated from the human gut. AB - We propose the main phenotypic characteristics and the complete genome sequence and annotation of Planococcus massiliensis strain ES2(T) (= CSUR P1103 = DSM 28915), the type strain of P. massiliensis sp. nov., isolated from a faeces sample collected from a healthy Senegalese man. It is an aerobic, Gram-positive, moderately halophilic, motile and rod-shaped bacterium. The 3 357 017 bp long genome exhibits a G+C content of 46.0% and contains 3357 protein-coding genes and 48 RNA genes. PMID- 27257488 TI - Noncontiguous finished genome sequence and description of Nocardioides massiliensis sp. nov. GD13(T). AB - Nocardioides massiliensis sp. nov strain GD13(T) is the type strain of N. massiliensis sp. nov., a new species within the genus Nocardioides. This strain was isolated from the faeces of a 62-year-old man admitted to intensive care for Guillain-Barre syndrome. Nocardioides massiliensis is a strictly aerobic Gram positive rod. Herein we describe the features of this bacterium, together with the complete genome sequence and annotation. The 4 006 620 bp long genome contains 4132 protein-coding and 47 RNA genes. PMID- 27257489 TI - Drug resistance and genetic characteristics of clinical isolates of staphylococci in Myanmar: high prevalence of PVL among methicillin-susceptible Staphylococcus aureus belonging to various sequence types. AB - Prevalence, drug resistance and genetic characteristics were analysed for a total of 128 clinical isolates of staphylococci obtained from a tertiary hospital in Myanmar. The dominant species were S. aureus (39%) and S. haemolyticus (35%), followed by S. epidermidis (6%) and S. saprophyticus (5%). The majority of S. haemolyticus isolates (71.1%) harboured mecA, showing high resistance rates to ampicillin, cephalosporins, erythromycin and levofloxacin, while methicillin resistant S. aureus (MRSA) was only 8% (four isolates) among S. aureus with type IV SCCmec. Panton-Valentine leukocidin (PVL) genes were detected in 20 isolates of S. aureus (40%), among which only one isolate was MRSA belonging to sequence type (ST) 88/agr-III/coa-IIIa, and the other 19 methicillin-susceptible S. aureus (MSSA) isolates were classified into six STs (ST88, ST121, ST1153, ST1155, ST1930, ST3206). An ST1153 MSSA isolate with PVL was revealed to belong to a novel coa type, XIIIa. ST121 S. aureus was the most common in the PVL-positive MSSA (47%, 9/19), harbouring genes of bone sialoprotein and variant of elastin binding protein as a distinctive feature. Although PVL-positive MSSA was susceptible to most of the antimicrobial agents examined, ST1930 isolates were resistant to erythromycin and levofloxacin. ST59 PVL-negative MRSA and MSSA had more resistance genes than other MRSA and PVL-positive MSSA, showing resistance to more antimicrobial agents. This study indicated higher prevalence of mecA associated with multiple drug resistance in S. haemolyticus than in S. aureus, and dissemination of PVL genes to multiple clones of MSSA, with ST121 being dominant, among hospital isolates in Myanmar. PMID- 27257490 TI - Drancourtella massiliensis gen. nov., sp. nov. isolated from fresh healthy human faecal sample from South France. AB - Strain GD1(T) gen. nov., sp. nov., is the type strain of the newly proposed genus and species Drancourtella massiliensis, belonging to the Clostridiales order. This strain, isolated from the stool of a healthy person, is a Gram-positive rod, oxygen intolerant and nonmotile, with spore-forming activity. The features of this organism and its genome sequence are described. The draft genome is 3 057 334 bp long with 45.24% G + C content; it contains 2861 protein-coding genes and 64 RNA genes. PMID- 27257491 TI - Presence of New Delhi metallo-beta-lactamase gene (NDM-1) in a clinical isolate of Acinetobacter junii in Argentina. PMID- 27257492 TI - First case of bone infection caused by Paenibacillus turicensis. AB - Paenibacillus spp. are bacteria present in the environment but are rarely isolated in humans. Here we report the first case of bone infection caused by Paenibacillus turicensis and a second case of human infection caused by this bacterium. PMID- 27257494 TI - Haematologic complications from human babesiosis: a case report. AB - Formerly known as Nantucket fever, babesiosis is increasing in incidence across the Northeastern United States. Because of its emerging health risk globally, it is important to be aware of its various presenting manifestations. We present the case of a middle-aged man with haemolytic anaemia from Babesia microti infection. PMID- 27257493 TI - Noncontiguous finished genome sequence and description of Paenibacillus antibioticophila sp. nov. GD11(T), the type strain of Paenibacillus antibioticophila. AB - Paenibacillus antibioticophila strain GD11(T) sp. nov. is the type strain of a new species within the genus Paenibacillus. This strain, whose genome is described here, was isolated from human faeces of a 63-year-old woman with multidrug-resistant tuberculosis who was receiving numerous antibiotics at the time of stool collection. P. antibioticophila is a Gram-positive aerobic bacterium. We describe here the features of this bacterium, together with the complete genome sequence and annotation. The 5 562 631 bp long genome contains 5084 protein-coding and 71 RNA genes. PMID- 27257495 TI - An unusual cause of necrosis and nasal septum perforation after septoplasty: Enterobacter cloacae. AB - A 20-year-old man with nasal obstruction underwent septoplasty due to nasal septal deviation. Nasal packs were inserted at the end of surgery and removed 48 hours after surgery. Twenty-four hours after removal of nasal packs, there was necrosis in both sides of septal mucosa and in bilateral inferior turbinates. Nasal swab culture was performed from both nasal cavities. Enterobacter cloacae was isolated from samples. Two weeks after surgery, nasal septum perforation was unavoidable. To our knowledge, this is the first case in literature describing septal mucosal necrosis caused by this pathogen after septoplasty. Mucosal necrosis and perforation as septoplasty complications should be kept in mind, the result of causes both common and, as in the present case, unusual. PMID- 27257496 TI - High-quality genome sequence and description of Bacillus ndiopicus strain FF3(T) sp. nov. AB - Strain FF3(T) was isolated from the skin-flora of a 39-year-old healthy Senegalese man. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry did not allow any identification. This strain exhibited a 16S rRNA sequence similarity of 96.8% with Bacillus massiliensis, the phylogenetically closest species with standing nomenclature. Using a polyphasic study made of phenotypic and genomic analyses, strain FF3(T) was Gram-positive, aeroanaerobic and rod shaped and exhibited a genome of 4 068 720 bp with a G+C content of 37.03% that coded 3982 protein-coding and 67 RNA genes (including four rRNA operons). On the basis of these data, we propose the creation of Bacillus ndiopicus sp. nov. PMID- 27257497 TI - Lack of Chlamydia-related bacteria among patients with community-acquired pneumonia. PMID- 27257498 TI - Burden of extensively drug-resistant and pandrug-resistant Gram-negative bacteria at a tertiary-care centre. AB - The emergence of resistance to multiple antimicrobial agents in Gram-negative bacteria is a significant threat to public health, as it restricts the armamentarium of the clinician against these infections. The aim of this study was to determine the burden of extensively drug-resistant (XDR) and pandrug resistant (PDR) Gram-negative bacteria at a tertiary-care centre. Antimicrobial susceptibility testing of 1240 clinical isolates of Gram-negative bacteria obtained from various clinical samples during the study period was carried out by the Kirby-Bauer disc diffusion method. Minimum inhibitory concentration of all antibiotics including tigecycline and colistin was determined by Vitek-2 automated susceptibility testing system. Out of 1240 isolates of Gram-negative bacteria, 112 isolates (9%) were resistant to all the antibiotics tested by Kirby Bauer disc diffusion method. This finding was corroborated by Vitek-2. In addition, Vitek-2 found that 67 isolates were resistant to all antibiotics except tigecycline and colistin. A total of 30 isolates were susceptible to only colistin, and four isolates were susceptible to only tigecycline. It was also found that six isolates (excluding five isolates of Proteus spp.) were resistant to both colistin and tigecycline. Thus, 101 (8.1%) out of 1240 isolates were XDR and 11 isolates (0.9%) were PDR. The findings of this study reveal increased burden of XDR and PDR Gram-negative bacteria in our centre. It also highlights the widespread dissemination of these bacteria in the community. This situation warrants the regular surveillance of antimicrobial resistance of Gram-negative bacteria and implementation of an efficient infection control program. PMID- 27257499 TI - First bacteraemic human infection with Escherichia albertii. AB - The facultative anaerobic Gram-negative species Escherichia albertii has been isolated from human faeces in gastrointestinal infection and from a range of wild bird species. Here we report the first case of a febrile infection associated with E. albertii bacteraemia in a 76-year-old woman with gastric dysplasia. PMID- 27257500 TI - Corrigendum to "Dolutegravir-based antiretroviral therapy in a severely overweight child with a multi-drug resistant human immunodeficiency virus infection. A case report and review" [New Microbes New Infect] 6 (2015) 1-4]. AB - [This corrects the article DOI: 10.1016/j.nmni.2015.02.003.]. PMID- 27257501 TI - Corrigendum to "The global threat of antimicrobial resistance: science for intervention" [New Microbes New Infect 6 (2015): 22-29]. AB - [This corrects the article DOI: 10.1016/j.nmni.2015.02.007.]. PMID- 27257502 TI - Overlap syndrome with Sjogren's syndrome and systemic sclerosis in a steel rolling mill worker: a case report. AB - BACKGROUND: There are few reports about work-related factors associated with Sjogren's syndrome. We report a case of overlap syndrome with Sjogren's syndrome and systemic sclerosis. CASE PRESENTATION: A 54-year-old man was admitted due to dyspnea on exertion. The results of physical examination and laboratory findings were compatible with Sjogren's syndrome with systemic sclerosis. The patient had no pre-existing autoimmune disease, and denied family history of autoimmune disease. The patient worked in the large-scale rolling department of a steel manufacturing company for 25 years. Hot rolling is a rolling process performed at between 1100 degrees C and 1200 degrees C, generating a high temperature and a large amount of fumes, involving jet-spraying of water throughout the process to remove the instantaneously generated oxide film and prevent the high generation of fumes. In this process, workers could be exposed to silica produced by thermal oxidation. Other potential toxic substances including nickel and manganese seemed to be less likely associated with the patient's clinical manifestations. CONCLUSIONS: Occupational exposure to silica seemed to be associated with the patient's clinical manifestations of overlap syndrome with Sjogren's syndrome and systemic sclerosis. Although the underlying mechanism is still unclear, autoimmune disease including Sjogren's syndrome affects women more often than men and there was no family history of autoimmune disease. These suggested that there was an association between occupational silica exposure and the disease of the patient. Future research about the association between long-term low dose exposure to silica and the development of autoimmune diseases should be encouraged. PMID- 27257503 TI - Inheritance and allelism of morphological traits in eastern redbud (Cercis canadensis L.). AB - Inheritance of purple, gold, and variegated foliage types, weeping architecture, and double flower was explored in F1, F2, and backcross families resulting from controlled hybridization of eastern redbud (Cercis canadensis L.). Potential allelic relationships were explored when possible. Inheritance analysis in families derived from controlled hybridization of 'Covey' (green leaf) and 'Forest Pansy' (purple leaf) suggest that purple leaf color and weeping architecture are both controlled by single recessive genes, for which the symbols pl1 and wp1 are proposed, respectively. Inheritance of gold leaf was explored in families of 'Covey' (green leaf) * 'Hearts of Gold' (gold leaf). Interpretation of inheritance of gold leaf in these families was confounded by the recovery of a leaf color phenotype in the F2 family unlike either parent. However, data suggested the action of a single locus controlling gold leaf color in 'Hearts of Gold', and that instability of gold leaf expression may be based on transposable element activity. Segregation of gold leaf in the F2 families of 'Texas White' [green leaf (C. canadensis var. texensis)] * 'JN2' [gold leaf (The Rising Sun)] did not fit a Mendelian ratio. Analysis of progeny of 'Silver Cloud' and 'Floating Clouds' (both showing white/green leaf variegation) with non-variegated cultivars demonstrated that variegation in 'Silver Cloud' is controlled by a single recessive nuclear gene, while variegation in 'Floating Clouds' is controlled by cytoplasmic factors. The symbol var1 is proposed for the gene controlling variegation in 'Silver Cloud'. Double flower in progeny derived from 'Flame' (double flower) suggested that double flower is dominant to single flower, and that 'Flame' is heterozygous at the double-flower locus, for which the symbol Df1 is proposed. Allelism studies showed that the gene controlling purple leaf in 'Forest Pansy' is allelic to the purple leaf gene in 'Greswan' and that the gene controlling weeping phenotype in 'Traveller' (C. canadensis var. texensis) is non-allelic to the weeping gene found in 'Covey'. Allelism of the gold leaf trait in 'Hearts of Gold' and 'JN2' was investigated, but no clear conclusions regarding allelism could be made due to recovery of leaf color phenotypes unlike either parent. PMID- 27257504 TI - Will the traditional horticultural breeding and genetics research be fairly valued in academia? PMID- 27257506 TI - Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy: a prospective cohort study. AB - BACKGROUND: Maternal obesity is accompanied by maternal and fetal complications during and after pregnancy. The risks seem to increase with degree of obesity. Leptin has been suggested to play a role in the development of obesity related complications. Whether maternal leptin levels differ between obese and morbidly obese women, during and after pregnancy, have to our knowledge not been previously described. Neither has the association between maternal leptin levels and gestational weight gain in obese women. The aim was to evaluate if maternal plasma leptin levels were associated with different degrees of maternal obesity and gestational weight gain. METHODS: Prospective cohort study including women categorized as obesity class I-III (n = 343) and divided into three gestational weight gain groups (n = 304). Maternal plasma leptin was measured at gestational week 15, 29 and 10 weeks postpartum. Maternal Body Mass Index (BMI) was calculated from early pregnancy weight. Gestational weight gain was calculated using maternal weight in delivery week minus early pregnancy weight. The mean value and confidence interval of plasma-leptin were analysed with a two-way ANOVA model. Interaction effect between BMI and gestational weight gain group was tested with a two-way ANOVA model. RESULTS: The mean maternal leptin concentrations were significantly higher in women with obesity class III compared to women in obesity class I, at all times when plasma leptin were measured. The mean leptin concentrations were also significantly higher in women with obesity class II compared to women in obesity class I, except in gestational week 29. There was no difference in mean levels of plasma leptin between the gestational weight gain groups. No significant interaction between BMI and gestational weight gain group was found. CONCLUSIONS: Plasma leptin levels during and after pregnancy were associated with obesity class but not with degree of gestational weight gain. These results are in concordance with epidemiological findings where the risk of obstetric complications increases with increased maternal obesity class. The effect on obstetric outcome by degree of gestational weight gain is less pronounced than the adverse effects associated with maternal obesity. PMID- 27257505 TI - A next-generation marker genotyping platform (AmpSeq) in heterozygous crops: a case study for marker-assisted selection in grapevine. AB - Marker-assisted selection (MAS) is often employed in crop breeding programs to accelerate and enhance cultivar development, via selection during the juvenile phase and parental selection prior to crossing. Next-generation sequencing and its derivative technologies have been used for genome-wide molecular marker discovery. To bridge the gap between marker development and MAS implementation, this study developed a novel practical strategy with a semi-automated pipeline that incorporates trait-associated single nucleotide polymorphism marker discovery, low-cost genotyping through amplicon sequencing (AmpSeq) and decision making. The results document the development of a MAS package derived from genotyping-by-sequencing using three traits (flower sex, disease resistance and acylated anthocyanins) in grapevine breeding. The vast majority of sequence reads (?99%) were from the targeted regions. Across 380 individuals and up to 31 amplicons sequenced in each lane of MiSeq data, most amplicons (83 to 87%) had <10% missing data, and read depth had a median of 220-244*. Several strengths of the AmpSeq platform that make this approach of broad interest in diverse crop species include accuracy, flexibility, speed, high-throughput, low-cost and easily automated analysis. PMID- 27257507 TI - Staining of cerebellar cortex granular layer interneurons with natural dye of Madder. AB - BACKGROUND: The objective of the present study was an investigation of root Rubia Tinctorum (Madder) as a natural dye to identification of granular layer interneurons of the rat cerebellum. METHODS: Seven to ten micrometre sections were collected from the cerebellum and stained only with Madder for 2, 24 and 48 h. Other sections were stained with Madder then with hematoxyllin, cresyl violet, eosin, light green. Microscopic identification of cells was performed based on cell morphology, reaction and binding of with the dye. All data were expressed as mean +/- SD in and significance was set at p <=0.05. RESULTS: Madder with alum as mordant resulted a deep red staining of interneurons. Unipolar brush cells (UBCs) were observed with a cell body diameter intermediate between granule and Golgi cells in the superficial layer of the granular layer. Golgi cells were identified almost as large as Purkinje cells with irregular rounded or polygonal morphology. Lugaro cells were observed as spindle-shaped cells adjacent to Purkinje layer. CONCLUSION: Results of the present study showed that mader could stain granular layer interneurons in cerebellum cortex of rat. PMID- 27257509 TI - Iris Metastasis in a Patient With Small Cell Lung Cancer: A Case Report. AB - INTRODUCTION: Small cell carcinoma constitutes the most aggressive type of lung cancer, with the greatest propensity for early disseminated disease. Although commonly neglected due to its rarity and the presence of other comorbidities, cases of iris metastasis from small cell lung cancer have been reported in the literature. CASE PRESENTATION: We present the case of a 76-year-old female. Once diagnosed, the patient already had disseminated disease with metastatic foci found in the spleen, liver, and brain. The patient received six cycles of combination carboplatin/etoposide chemotherapy, followed by cranial irradiation. After an initial response, two months after the completion of cranial irradiation, the patient complained of visual impairment and was referred to an ophthalmologist. A diagnosis of secondary glaucoma was made, caused by metastasis to the left iris. CONCLUSIONS: Physicians should be aware of this rare site of metastasis. Early diagnosis is of paramount importance in order to effectively prevent the significant morbidity this condition can cause if left untreated. PMID- 27257508 TI - Biomimetic microenvironments for regenerative endodontics. AB - Regenerative endodontics has been proposed to replace damaged and underdeveloped tooth structures with normal pulp-dentin tissue by providing a natural extracellular matrix (ECM) mimicking environment; stem cells, signaling molecules, and scaffolds. In addition, clinical success of the regenerative endodontic treatments can be evidenced by absence of signs and symptoms; no bony pathology, a disinfected pulp, and the maturation of root dentin in length and thickness. In spite of the various approaches of regenerative endodontics, there are several major challenges that remain to be improved: a) the endodontic root canal is a strong harbor of the endodontic bacterial biofilm and the fundamental etiologic factors of recurrent endodontic diseases, (b) tooth discolorations are caused by antibiotics and filling materials, (c) cervical root fractures are caused by endodontic medicaments, (d) pulp tissue is not vascularized nor innervated, and (e) the dentin matrix is not developed with adequate root thickness and length. Generally, current clinical protocols and recent studies have shown a limited success of the pulp-dentin tissue regeneration. Throughout the various approaches, the construction of biomimetic microenvironments of pulp dentin tissue is a key concept of the tissue engineering based regenerative endodontics. The biomimetic microenvironments are composed of a synthetic nano scaled polymeric fiber structure that mimics native pulp ECM and functions as a scaffold of the pulp-dentin tissue complex. They will provide a framework of the pulp ECM, can deliver selective bioactive molecules, and may recruit pluripotent stem cells from the vicinity of the pulp apex. The polymeric nanofibers are produced by methods of self-assembly, electrospinning, and phase separation. In order to be applied to biomedical use, the polymeric nanofibers require biocompatibility, stability, and biodegradability. Therefore, this review focuses on the development and application of the biomimetic microenvironments of pulp dentin tissue among the current regenerative endodontics. PMID- 27257510 TI - Propylthiouracil-Induced Vasculitis With Alveolar Hemorrhage Confirmed by Clinical, Laboratory, Computed Tomography, and Bronchoscopy Findings: A Case Report and Literature Review. AB - INTRODUCTION: Propylthiouracil (PTU) is commonly used to treat hyperthyroidism and can induce antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Although this is a rare side effect, ANCA-associated vasculitis can progress to severe disease if its diagnosis and treatment are delayed, leading to a poor prognosis. CASE PRESENTATION: A 43-year-old woman with Graves' disease developed pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) associated with ANCA against myeloperoxidase and proteinase-3 that was confirmed by computed tomography (CT) and bronchoscopy and treated with PTU. The symptoms and signs of alveolar hemorrhage were rapidly resolved after PTU withdrawal and treatment with corticosteroids. After 6 months of follow-up, the patient maintained complete ANCA-negative clinical remission status, as confirmed by normal CT and bronchoscopy findings. To our knowledge, this is the first documented case of bronchoscopic comparison of PTU-induced DAH before and after steroid treatment. CONCLUSIONS: Patients treated with PTU should be closely monitored and followed up, even if the drug has been used for several years. When patients develop progressive dyspnea with alveolar opacities on chest imaging that cannot be explained otherwise, alveolar hemorrhage should be an important differential diagnosis while investigating the case. Early diagnosis and prompt discontinuation of the PTU treatment are essential for improving patient outcomes. PMID- 27257511 TI - Distribution of Human Papillomavirus Genotypes in Iranian Women According to the Severity of the Cervical Lesion. AB - BACKGROUND: Persistent infection with high-risk human papillomavirus (HPV) has been recognized as a major cause of cervical cancer. Distribution of HPV genotypes may differ according to the geographic region and the severity of the cervical lesion. Determining HPV genotypes' specific distribution is useful for HPV surveillance and control programs. However, little is known about the distribution of HPV genotypes in Iranian women. OBJECTIVES: The aim of this study was to determine the distribution of HPV genotypes in Iranian women with different grades of cervical lesions. PATIENTS AND METHODS: From 2011 to 2013, a total of 436 Iranian women with convenience sampling strategy were included in this cross-sectional study. In detail, 287 women negative for intraepithelial lesion or malignancy, 32 with atypical squamous cells of undetermined significance (ASCUS), 50 with low-grade squamous intraepithelial lesion (LSIL), 44 with high-grade squamous intraepithelial lesion (HSIL), and 23 with cervical cancer were evaluated in this investigation. HPV genotypes were determined by INNO-LiPA HPV Genotyping Extra assay. RESULTS: In total, HPV infection was detected in 45.4% of the cases. The most common high-risk HPV (HR-HPV) genotype was HPV-16 (32.8%), followed by HPV-53 (9.1%). Within low-risk (LR-HPV) genotypes HPV-6 (22.2%) and HPV-44 (6.1%) were the most prevalent. HPV-16 was the predominant genotype in cases with cervical cancer (56.5%), ASCUS (34.4%), and HSIL (34.1%). HPV-6 was the most common genotype in normal cases (9.1%) and LSIL patients (18%). The prevalence of HPV positivity was significantly higher in cases with high-grade lesions (>= HSIL) (64.2%) than in normal/LSIL (37.3%) (P = 0.033). The rate of HR-HPV infection was significantly higher in >= HSIL cases (61.2%) than normal/LSIL (27.9%) (P = 0.003). CONCLUSIONS: This study describes robust information on the distribution of HPV genotypes among Iranian women with and without cervical lesions. The present data may be of importance for designing future public health strategies, including HPV vaccination programs. PMID- 27257512 TI - The Effects of Oral Cryotherapy on Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Transplantation of Blood Stem Cells: A Clinical Trial. AB - BACKGROUND: Oral mucositis is one of the irritating side effects of chemotherapy in patients undergoing bone marrow transplantation. However, up until now, the common methods of oral mucositis therapy have failed to show significant effects. OBJECTIVES: The aim of this study was to investigate the effects of local cryotherapy on the intensity of chemotherapy-induced oral mucositis in autologous bone marrow transplantation patients. PATIENTS AND METHODS: In this single, blinded, randomized clinical trial, 29 patients undergoing stem cell transplantation in Iran were selected by convenience sampling, and randomly allocated to control (n = 13) and intervention groups (n = 16). In the intervention group, cryotherapy was applied, while the control group received a normal saline mouthwash. The severity of the mucositis and neutrophil rate were investigated in five periods, based on the world health organization (WHO) scales. The data were analyzed using descriptive statistics, the Mann-Whitney test, repeated measures analysis of variance (ANOVA), and linear regression. RESULTS: In both groups, the mucositis reached its peak intensity on the 7th day, and the least intensity was obtained on the 21st day. The neutrophil rate reached the minimum value on the 7th day, then increased up to the 21st day. The two groups showed no significant differences between the mucositis severity on the 14th and 21st days (P = 0.164), while the severity of the mucositis in the cryotherapy group was significantly less than that in the saline mouthwash group (1.81 < 2.54 and 0.13 < 0.92, respectively) on the 7th and 14th days (P < 0.05). There was no significant difference in the neutrophil rate between the groups. CONCLUSIONS: The results showed that cryotherapy is more effective than the saline mouthwash in reducing the severity of mucositis. This method is recommended for the prevention of mucositis in bone marrow transplantation. PMID- 27257513 TI - Clinical Findings and Autopsy of a Preterm Infant with Breast Milk-Acquired Cytomegalovirus Infection. AB - Background Nonpasteurized, nonfrozen, fresh breast milk from mothers with positive cytomegalovirus (CMV) serology was initially contraindicated to very low birth-weight infants because of the risk of milk-acquired CMV infection. Recently, the severity of this infection was increasingly discussed and the international guidelines now differ. Since 2012, the American Academy of Pediatrics has recommended nutrition through raw breast milk for all preterm infants. Case We report the case of an infant born prematurely at 27 weeks and 4 days and fed with raw breastmilk from day 12 of life (D12). He presented with a late-onset of CMV infection from D39. The CMV polymerase chain reaction (PCR), negative on D3, was strongly positive on D49, as well as the PCR on breast milk. He had CMV-specific immunoglobulin (Ig) M while his mother had only CMV-specific IgG. On D52, he deteriorated further with septic shock, and a fatal cardiac arrest on D54. His twin presented an asymptomatic CMV infection. The autopsy and histological examination showed evidence of numerous organ damage caused by CMV (with differences compared with congenital infection) but no evidence of bacterial infection. Conclusion Although rare, postnatal CMV infections transmitted by raw breast milk given to very low-birthweight infants can have dramatic consequences. PMID- 27257514 TI - Using Portable Transducers to Measure Tremor Severity. AB - BACKGROUND: Portable motion transducers, suitable for measuring tremor, are now available at a reasonable cost. The use of these transducers requires knowledge of their limitations and data analysis. The purpose of this review is to provide a practical overview and example software for using portable motion transducers in the quantification of tremor. METHODS: Medline was searched via PubMed.gov in December 2015 using the Boolean expression "tremor AND (accelerometer OR accelerometry OR gyroscope OR inertial measurement unit OR digitizing tablet OR transducer)." Abstracts of 419 papers dating back to 1964 were reviewed for relevant portable transducers and methods of tremor analysis, and 105 papers written in English were reviewed in detail. RESULTS: Accelerometers, gyroscopes, and digitizing tablets are used most commonly, but few are sold for the purpose of measuring tremor. Consequently, most software for tremor analysis is developed by the user. Wearable transducers are capable of recording tremor continuously, in the absence of a clinician. Tremor amplitude, frequency, and occurrence (percentage of time with tremor) can be computed. Tremor amplitude and occurrence correlate strongly with clinical ratings of tremor severity. DISCUSSION: Transducers provide measurements of tremor amplitude that are objective, precise, and valid, but the precision and accuracy of transducers are mitigated by natural variability in tremor amplitude. This variability is so great that the minimum detectable change in amplitude, exceeding random variability, is comparable for scales and transducers. Research is needed to determine the feasibility of detecting smaller change using averaged data from continuous long-term recordings with wearable transducers. PMID- 27257515 TI - Cortical folding of the preterm brain: a longitudinal analysis of extremely preterm born neonates using spectral matching. AB - INTRODUCTION: Infants born extremely preterm (<28 weeks of gestation) are at risk of significant neurodevelopmental sequelae. In these infants birth coincides with a period of rapid brain growth and development, when the brain is also vulnerable to a range of insults. Mapping these changes is crucial for identifying potential biomarkers to predict early impairment. METHODS: In this study we use surface based spectral matching techniques to find an intrasubject longitudinal surface correspondence between the white-grey matter boundary at 30 and 40 weeks equivalent gestational age in nine extremely preterm born infants. RESULTS: Using the resulting surface correspondence, we identified regions that undergo more cortical folding of the white-grey matter boundary during the preterm period by looking at changes in well-known curvature measures. We performed Hotelling T(2) statistics to evaluate the significance of our findings. DISCUSSION: The prefrontal and temporal lobes exhibit most development during the preterm period, especially in the left hemisphere. Such correspondences are a promising result as longitudinal measurements of change in cortical folding could provide insightful information about the mechanical properties of the underlying tissue and may be useful in inferring changes during growth and development in this vulnerable period. PMID- 27257517 TI - The stroke east Saxony pilot project for organized post-stroke care: a case control study. AB - BACKGROUND: Low adherence to secondary prevention guidelines in stroke survivors may increase the risk for recurrent stroke and adversely impact quality of life. We aimed to determine the feasibility of a self-developed standardized post stroke pathway and its impact on secondary stroke prevention and long-term outcome in patients with acute stroke. METHODS: Consecutive patients with acute stroke were prospectively included in a standardized post-stroke pathway accomplished through a single certified CM (case manager), which comprised educational discussions and quarterly checkups for vascular risk factors and adherence to antithrombotic/anticoagulant medication in addition to usual care. At 12 months, we compared achieved target goals for secondary prevention, functional outcome, stroke recurrence, and vascular death with age- and gender matched controls that received only usual care after stroke. RESULTS: We included 45 cases and 45 controls. The following target goals were more frequently achieved in CM-patients than in controls: blood pressure (100% vs. 46.2%, P < 0.001), cholesterol (100% vs. 74.4%, P < 0.001), and body mass index (67.4% vs. 46.2%, P = 0.052). The CM-intervention emerged as an independent predictor of favorable functional outcome (mRS <= 2) at 12 months after adjusting for stroke severity and systemic thrombolysis (OR: 4.27; 95%CI:1.2-15.21; P = 0.025). Quality of life was rated significantly higher in CM-patients than in controls (P = 0.049). As opposed to controls, none of the cases experienced a recurrent stroke (0% vs. 13.3%; P = 0.026) or suffered from vascular death (0% vs. 6.7%; P = 0.242). CONCLUSIONS: Our pilot data suggest that organized post-stroke care enhances achievement of secondary prevention goals. Its possible effect on stroke recurrence, long-term disability, and quality of life is currently investigated in a prospective cohort study. PMID- 27257516 TI - Deficits in Visual System Functional Connectivity after Blast-Related Mild TBI are Associated with Injury Severity and Executive Dysfunction. AB - INTRODUCTION: Approximately, 275,000 American service members deployed to Iraq or Afghanistan have sustained a mild traumatic brain injury (mTBI), with 75% of these incidents involving an explosive blast. Visual processing problems and cognitive dysfunction are common complaints following blast-related mTBI. METHODS: In 127 veterans, we examined resting fMRI functional connectivity (FC) of four key nodes within the visual system: lateral geniculate nucleus (LGN), primary visual cortex (V1), lateral occipital gyrus (LO), and fusiform gyrus (FG). Regression analyses were performed (i) to obtain correlations between time series from each seed and all voxels in the brain, and (ii) to identify brain regions in which FC variability was related to blast mTBI severity. Blast-related mTBI severity was quantified as the sum of the severity scores assigned to each of the three most significant blast-related injuries self-reported by subjects. Correlations between FC and performance on executive functioning tasks were performed across participants with available behavioral data (n = 94). RESULTS: Greater blast mTBI severity scores were associated with lower FC between: (A) LGN seed and (i) medial frontal gyrus, (ii) lingual gyrus, and (iii) right ventral anterior nucleus of thalamus; (B) V1 seed and precuneus; (C) LO seed and middle and superior frontal gyri; (D) FG seed and (i) superior and medial frontal gyrus, and (ii) left middle frontal gyrus. Finally, lower FC between visual network regions and frontal cortical regions predicted worse performance on the WAIS digit-symbol coding task. CONCLUSION: These are the first published results that directly illustrate the relationship between blast-related mTBI severity, visual pathway neural networks, and executive dysfunction - results that highlight the detrimental relationship between blast-related brain injury and the integration of visual sensory input and executive processes. PMID- 27257519 TI - Single-Cell-State Culture of Human Pluripotent Stem Cells Increases Transfection Efficiency. AB - Efficient gene transfer into human pluripotent stem cells (hPSCs) holds great promise for regenerative medicine and pharmaceutical development. In the past decade, various methods were developed for gene transfer into hPSCs; however, hPSCs form tightly packed colonies, making gene transfer difficult. In this study, we established a stable culture method of hPSCs at a single-cell state to reduce cell density and investigated gene transfection efficiency followed by gene editing efficiency. hPSCs cultured in a single-cell state were transfected using nonliposomal transfection reagents with plasmid DNA or mRNA encoding enhanced green fluorescent protein. We found that most cells (DNA > 90%; mRNA > 99%) were transfected without the loss of undifferentiated PSC marker expression or pluripotency. Moreover, we demonstrated an efficient gene editing method using transcription activator-like effector nucleases (TALENs) targeting the adenomatous polyposis coli (APC) gene. Our new method may improve hPSC gene transfer techniques, thus facilitating their use for human regenerative medicine. PMID- 27257520 TI - Transforming the Milieu of Cancer. PMID- 27257521 TI - The Placebo Effect: A Conversation With Dr Irving Kirsch. PMID- 27257518 TI - Variable activation in striatal subregions across components of a social influence task in young adult cannabis users. AB - INTRODUCTION: Decades of research have demonstrated the importance of social influence in initiation and maintenance of drug use, but little is known about neural mechanisms underlying social influence in young adults who use recreational drugs. METHODS: To better understand whether the neural and/or behavioral response to social influence differs in young adults using illicit drugs, 20 marijuana-using young adults (MJ) aged 18-25, and 20 controls (CON) performed a decision-making task in the context of social influence, while they underwent functional magnetic resonance imaging scans. A priori analyses focused on the nucleus accumbens (NAc), with post hoc analyses in the rest of the striatum. In this task, participants could choose to either follow or go against group influence. RESULTS: When subjects applied social information to response choice selection (independent of following or going against group influence), we observed activation in the middle striatum (caudate), in the MJ group only, that extended ventrally into the NAc. MJ users but not CON showed greater activation in the NAc but not the caudate while making choices congruent with group influence as opposed to choices going against group influence. Activation in the NAc when following social influence was associated with amount of drug use reported. In contrast, during the feedback phase of the task we observed significant NAc activation in both MJ and CON, along with dorsal caudate activation only in MJ participants. This NAc activation did not correlate with drug use. CONCLUSIONS: This study shows that MJ users, but not CON, show differential brain activation across striatal subregions when applying social information to make a decision, following versus going against a group of peers, or receiving positive feedback. The current work suggests that differential neural sensitivity to social influence in regions such as the striatum may contribute to the development and/or maintenance of marijuana use. PMID- 27257522 TI - Is the Efficacy of Antidepressants Truly a Myth? PMID- 27257523 TI - "Nothing About Me Without Me": New Perspectives on Case Reports. PMID- 27257524 TI - Successful Treatment of HER2-neu-positive Breast Cancer With Paclitaxel and Trastuzumab Supplemented With Turkey Tail Mushrooms and Community Support. PMID- 27257525 TI - Patient Perspective: An Interview. PMID- 27257526 TI - Trametes versicolor (Turkey Tail Mushrooms) and the Treatment of Breast Cancer. PMID- 27257527 TI - Complete Spontaneous Regression of Merkel Cell Carcinoma Metastatic to the Liver: Did Lifestyle Modifications and Dietary Supplements Play a Role? PMID- 27257528 TI - The Use of Music Therapy During the Treatment of Cancer Patients: A Collection of Evidence. AB - BACKGROUND: Music therapy is one of the oldest forms of creative art therapy and has been shown to have effects in different clinical and therapeutic settings, such as schizophrenia, pain, cardiovascular parameters, and dementia. This article provides an overview of some of the recent findings in this field and also reports two single case vignettes that offer insight into day-to-day applications of clinical music therapy. MATERIAL AND METHODS: For the collection of clinical studies of music therapy in oncology, the databases AMED, CAIRSS, EMBASE, MEDLINE, PsychINFO, and PSYNDEX were searched with the terms "Study OR Trial" AND "Music Therapy" AND "Cancer OR Oncolog$." Studies were analyzed with respect to their design, setting and interventions, indications, patients, and outcomes. In addition, two case vignettes present the application of music therapy for a child with leukemia and an adult patient with breast cancer. RESULTS: We found a total of 12 clinical studies conducted between 2001 and 2011 comprised of a total of 922 patients. Eight studies had a randomized controlled design, and four studies were conducted in the field of pediatric oncology. Studies reported heterogeneous results on short-term improvements in patients' mood and relaxation and reduced exhaustion and anxiety as well as in coping with the disease and cancer-related pain. Case descriptions showed similar effects in expressing emotions, opening up new goals, and turning the mind toward a healthy process and away form a disease-centered focus. CONCLUSION: The use of music therapy in the integrative treatment of cancer patients is a therapeutic option whose salutogenetic potential is shown in many case studies such as those presented here. Study results, however, did not draw a conclusive picture of the overall effect of music therapy. In addition to further clinical trials, the evidence mosaic should be complemented with qualitative studies, single case descriptions, and basic research. PMID- 27257529 TI - A Randomized Controlled Pilot Study Assessing Feasibility and Impact of Yoga Practice on Quality of Life, Mood, and Perceived Stress in Women With Newly Diagnosed Breast Cancer. AB - BACKGROUND: A breast cancer diagnosis can entail numerous physical and psychosocial challenges. Yoga practice (YP) may contribute to improved well-being for these patients. PRIMARY STUDY OBJECTIVE: Investigate feasibility and impact of YP on quality of life (QoL), mood, fatigue, and perceived stress immediately after breast cancer diagnosis. METHODS: Thirty women were randomly assigned to a yoga group (YG) or control group (CG) immediately after cancer diagnosis. SETTING: Pilot study conducted at an academic medical center breast clinic. PARTICIPANTS: Females (N = 30) who received a biopsy-proven breast cancer diagnosis without metastatic disease. INTERVENTION YG: One individual YP session at baseline, then 2 individual and 8 weekly group sessions followed by weekly gentle yoga at home (DVD). Questionnaires and saliva samples (ie, cortisol) completed at baseline and 12 weeks postdiagnosis. RESULTS: Both groups reported significant improvements in QoL postintervention but with no significant difference between groups. Emotional well-being, mood-related tension-anxiety, depression-dejection, and confusion-bewilderment scores improved for both groups, and cortisol and cortisone levels decreased. Lumpectomies were prevalent with YG (67%) and CG (47%). YP was rated as "very effective," providing relaxation (85%), stress relief (69%), and reduced muscle tension/general feeling of wellness (each 62%). CONCLUSION: Feasibility of YP immediately after breast cancer diagnosis was good. Improvement in emotional well-being, anxiety, depression, and levels of confusion was found in both groups. To our knowledge, this is the first study examining the impact of YP immediately after breast cancer diagnosis. Further research in this area is warranted. PMID- 27257530 TI - Repeatability of Pulse Diagnosis and Body Constitution Diagnosis in Traditional Indian Ayurveda Medicine. AB - In Ayurveda, pulse diagnosis and body constitution diagnosis have a long historical use; still, there is lack of quantitative measure of the reliability of these diagnostic methods. Reliability means consistency of information. Consistent diagnosis leads to consistent treatment and is important for clinical practice, education, and research. The objective of this study is to study the methodology to evaluate the test-retest reliability (repeatability) of pulse diagnosis and body constitution diagnosis. A double-blinded, controlled, clinical trial was conducted in Copenhagen. The same doctor, an expert in Ayurvedic pulse diagnosis, examined the pulse and body constitution of 17 healthy participants twice, in random order without seeing them. A metric on pulse and body constitution variables was developed. Cohen's weighted kappa statistic was used as a measure of intra-rater reliability. Permutation tests were used to test the hypothesis of homogeneous diagnosis (ie, the doctor's diagnosis does not depend on the subject). The hypothesis of homogeneous classification was rejected on the 5% significance level (P values of .02 and .001, respectively, for pulse and body constitution diagnosis). According to the Landis and Koch scale, values of the weighted kappa for pulse diagnosis (P = .42) and body constitution diagnosis (P = .65) correspond to "moderate" and "substantial" agreement, respectively. There was a reasonable level of consistency between 2 pulse and body constitution diagnoses. Further studies are required to quantify inter-subject and intra subject agreement for greater understanding of reliability of pulse and body constitution diagnosis. PMID- 27257531 TI - Call for Articles. PMID- 27257532 TI - Resilience Training Program Reduces Physiological and Psychological Stress in Police Officers. AB - Research suggests that police work is among the most stressful occupations in the world and officers typically suffer a variety of physiological, psychological, and behavioral effects and symptoms. Officers operating under severe or chronic stress are likely to be at greater risk of error, accidents, and overreactions that can compromise their performance, jeopardize public safety, and pose significant liability costs to the organization. Therefore, this study explored the nature and degree of physiological activation typically experienced of officers on the job and the impact of the Coherence Advantage resilience and performance enhancement training on a group of police officers from Santa Clara County, California. Areas assessed included vitality, emotional well-being, stress coping and interpersonal skills, work performance, workplace effectiveness and climate, family relationships, and physiological recalibration following acute stressors. Physiological measurements were obtained to determine the real time cardiovascular impact of acutely stressful situations encountered in highly realistic simulated police calls used in police training and to identify officers at increased risk of future health challenges. The resilience-building training improved officers' capacity to recognize and self-regulate their responses to stressors in both work and personal contexts. Officers experienced reductions in stress, negative emotions, depression, and increased peacefulness and vitality as compared to a control group. Improvements in family relationships, more effective communication and cooperation within work teams, and enhanced work performance also were noted. Heart rate and blood pressure measurements taken during simulated police call scenarios showed that acutely stressful circumstances typically encountered on the job result in a tremendous degree of physiological activation, from which it takes a considerable amount of time to recover. Autonomic nervous system assessment based on heart rate variability (HRV) analysis of 24-hour electrocardiogram (ECG) recordings revealed that 11% of the officers were at higher risk for sudden cardiac death and other serious health challenges. This is more than twice the percentage typically found in the general population and is consistent with epidemiological data indicating that police officers have more than twice the average incidence of cardiovascular-related disease. The data suggest that training in resilience building and self regulation skills could significantly benefit police organizations by improving judgment and decision making and decreasing the frequency of onthe-job driving accidents and the use of excessive force in high-stress situations. Potential outcomes include fewer citizens' complaints, fewer lawsuits, decreased organizational liabilities, and increased community safety. Finally, this study highlights the value of 24-hour HRV analysis as a useful screening tool to identify officers who are at increased risk, so that efforts can be made to reverse or prevent the onset of disease in these individuals. PMID- 27257534 TI - From Reductionism to Holism: Systems-oriented Approaches in Cancer Research. AB - Somatic mutation theory of cancer has directed cancer research during the last century. A deluge of information on cellular, molecular, and genetic behavior was uncovered, but so was a mind-numbing complexity that still challenges research and concepts, and expectations in the war on cancer have by and large not been fulfilled. A change of paradigm beyond reductionism has been called for, especially as research ubiquitously points at the importance of tissue, microenvironment, extracellular matrix, embryonic and morphogenetic fields, and fields of tissue maintenance and organization in the processes of carcinogenesis, cancer control, and cancer progression, as well as in the control of cellular and genetic behavior. Holistic, organismic systems concepts open new perspectives for cancer research and treatment, as well as general biological understanding. PMID- 27257536 TI - An enigmatic aquatic snake from the Cenomanian of Northern South America. AB - We report the first record of a snake from the Cretaceous of northern South America. The remains come from the La Luna Formation (La Aguada Member, Cenomanian of Venezuela) and consist of several vertebrae, which belong to the precloacal region of the vertebral column. Comparisons to extant and extinct snakes show that the remains represent a new taxon, Lunaophis aquaticus gen. et sp nov. An aquatic mode of life is supported by the ventral position of the ribs, indicating a laterally compressed body. The systematic relationships of this new taxon are difficult to determine due to the scarcity of fossil material; it is, however, a representative of an early lineage of snakes that exploited tropical marine pelagic environments, as reflected by the depositional conditions of the La Aguada Member. Lunaophis is also the first aquatic snake from the Cenomanian found outside of the African and European Tethyan and Boreal Zones. PMID- 27257537 TI - Forest birds respond to the spatial pattern of exurban development in the Mid Atlantic region, USA. AB - Housing development beyond the urban fringe (i.e., exurban development) is one of the fastest growing forms of land-use change in the United States. Exurban development's attraction to natural and recreational amenities has raised concerns for conservation and represents a potential threat to wildlife. Although forest-dependent species have been found particularly sensitive to low housing densities, it is unclear how the spatial distribution of houses affects forest birds. The aim of this study was to assess forest bird responses to changes in the spatial pattern of exurban development and also to examine species responses when forest loss and forest fragmentation were considered. We evaluated landscape composition around North American Breeding Bird Survey stops between 1986 and 2009 by developing a compactness index to assess changes in the spatial pattern of exurban development over time. Compactness was defined as a measure of how clustered exurban development was in the area surrounding each survey stop at each time period considered. We used Threshold Indicator Taxa Analysis to detect the response of forest and forest-edge species in terms of occurrence and relative abundance along the compactness gradient at two spatial scales (400-m and 1-km radius buffer). Our results showed that most forest birds and some forest-edge species were positively associated with high levels of compactness at the larger spatial scale; the proportion of forest in the surrounding landscape also had a significant effect when forest loss and forest fragmentation were accounted for. In contrast, the spatial configuration of exurban development was an important predictor of occurrence and abundance for only a few species at the smaller spatial scale. The positive response of forest birds to compactness at the larger scale could represent a systematic trajectory of decline and could be highly detrimental to bird diversity if exurban growth continues and creates more compacted development. PMID- 27257535 TI - Sequence/structural analysis of xylem proteome emphasizes pathogenesis-related proteins, chitinases and beta-1, 3-glucanases as key players in grapevine defense against Xylella fastidiosa. AB - Background. Xylella fastidiosa, the causative agent of various plant diseases including Pierce's disease in the US, and Citrus Variegated Chlorosis in Brazil, remains a continual source of concern and economic losses, especially since almost all commercial varieties are sensitive to this Gammaproteobacteria. Differential expression of proteins in infected tissue is an established methodology to identify key elements involved in plant defense pathways. Methods. In the current work, we developed a methodology named CHURNER that emphasizes relevant protein functions from proteomic data, based on identification of proteins with similar structures that do not necessarily have sequence homology. Such clustering emphasizes protein functions which have multiple copies that are up/down-regulated, and highlights similar proteins which are differentially regulated. As a working example we present proteomic data enumerating differentially expressed proteins in xylem sap from grapevines that were infected with X. fastidiosa. Results. Analysis of this data by CHURNER highlighted pathogenesis related PR-1 proteins, reinforcing this as the foremost protein function in xylem sap involved in the grapevine defense response to X. fastidiosa. beta-1, 3-glucanase, which has both anti-microbial and anti-fungal activities, is also up-regulated. Simultaneously, chitinases are found to be both up and down-regulated by CHURNER, and thus the net gain of this protein function loses its significance in the defense response. Discussion. We demonstrate how structural data can be incorporated in the pipeline of proteomic data analysis prior to making inferences on the importance of individual proteins to plant defense mechanisms. We expect CHURNER to be applicable to any proteomic data set. PMID- 27257539 TI - Conditions during adulthood affect cohort-specific reproductive success in an Arctic-nesting goose population. AB - Variation in fitness between individuals in populations may be attributed to differing environmental conditions experienced among birth (or hatch) years (i.e., between cohorts). In this study, we tested whether cohort fitness could also be explained by environmental conditions experienced in years post-hatch, using 736 lifelong resighting histories of Greenland white-fronted geese (Anser albifrons flavirostris) marked in their first winter. Specifically, we tested whether variation in age at first successful reproduction, the size of the first successful brood and the proportion of successful breeders by cohort was explained by environmental conditions experienced on breeding areas in west Greenland during hatch year, those in adulthood prior to successful reproduction and those in the year of successful reproduction, using North Atlantic Oscillation indices as proxies for environmental conditions during these periods. Fifty-nine (8%) of all marked birds reproduced successfully (i.e., were observed on wintering areas with young) only once in their lifetime and 15 (2%) reproduced successfully twice or thrice. Variation in age at first successful reproduction was explained by the environmental conditions experienced during adulthood in the years prior to successful reproduction. Birds bred earliest (mean age 4) when environmental conditions were 'good' prior to the year of successful reproduction. Conversely, birds successfully reproduced at older ages (mean age 7) if they experienced adverse conditions prior to the year of successful reproduction. Hatch year conditions and an interaction between those experienced prior to and during the year of successful reproduction explained less (marginally significant) variation in age at first successful reproduction. Environmental conditions did not explain variation in the size of the first successful brood or the proportion of successful breeders. These findings show that conditions during adulthood prior to the year of successful reproduction are most important in determining the age at first successful reproduction in Greenland white-fronted geese. Very few birds bred successfully at all (most only once), which suggests that May environmental conditions on breeding areas have cohort effects that influence lifetime (and not just annual) reproductive success. PMID- 27257540 TI - Response of marine copepods to a changing tropical environment: winners, losers and implications. AB - Background. Climate change concurrent with anthropogenic disturbances can initiate serial changes that reverberate up the food chain with repercussions for fisheries. To date, there is no information available concerning the combined effects of global warming and human impacts on tropical marine food webs. While temperate copepods respond differently to warming and environmental stressors, the extent to which tropical copepods can adapt to rising temperature of already warm waters remains unknown. We hypothesize that sea warming and other anthropogenic disturbances over the long term will have the greatest impact on the copepod community in nearshore waters where their effects are accentuated, and therefore vulnerable and resilient species could be identified. Methods. Zooplankton samples were collected during two time periods (1985-86 and 2014-15) interposed by marked anthropogenic disturbances, and at the same five stations located progressively from inshore to offshore in Klang Strait, Malaysia, following the asymmetrical before-after-control-impact (BACI) design. Copepods were identified to species, and results were interpreted by univariate (ANOVA) and multivariate (PERMANOVA, PCO) analyses of the computed species abundance and diversity measures. Results. Copepod total abundance was not significantly different among stations but higher after disturbance than before disturbance. However, changes in the abundance of particular species and the community structure between time periods were dramatic. Coastal large-bodied calanoid species (e.g., Acartia spinicauda, Calanopia thompsoni, Pseudodiaptomus bowmani and Tortanus forcipatus) were the most vulnerable group to disturbance. This however favored the opportunistic species (e.g., Oithona simplex, O. attenuata, Hemicyclops sp., Pseudomacrochiron sp. and Microsetella norvegica). Small-bodied copepods (e.g., Paracalanus sp., Parvocalanus crassirostris and Euterpina acutifrons) were unaffected. Centropages tenuiremis was likely an introduced species. There was no significant loss in species richness of copepods despite the dramatic changes in community structure. Discussion. Sea warming and other human-induced effects such as eutrophication, acidification and coastal habitat degradation are likely the main factors that have altered copepod community structure. The large-bodied estuarine and coastal calanoid copepods are surmised to be vulnerable to eutrophication and hypoxia, while both resilient and opportunistic species are largely unaffected by, or adaptable to, degraded coastal environments and observed sea surface temperature (SST) rise. It is forecasted that SST rise with unmitigated anthropogenic impacts will further reduce large-bodied copepod species the favoured food for fish larvae with dire consequences for coastal fish production. PMID- 27257538 TI - Similarities between decapod and insect neuropeptidomes. AB - Background. Neuropeptides are important regulators of physiological processes and behavior. Although they tend to be generally well conserved, recent results using trancriptome sequencing on decapod crustaceans give the impression of significant differences between species, raising the question whether such differences are real or artefacts. Methods. The BLAST+ program was used to find short reads coding neuropeptides and neurohormons in publicly available short read archives. Such reads were then used to find similar reads in the same archives, and the DNA assembly program Trinity was employed to construct contigs encoding the neuropeptide precursors as completely as possible. Results. The seven decapod species analyzed in this fashion, the crabs Eriocheir sinensis, Carcinus maenas and Scylla paramamosain, the shrimp Litopenaeus vannamei, the lobster Homarus americanus, the fresh water prawn Macrobrachium rosenbergii and the crayfish Procambarus clarkii had remarkably similar neuropeptidomes. Although some neuropeptide precursors could not be assembled, in many cases individual reads pertaining to the missing precursors show unambiguously that these neuropeptides are present in these species. In other cases, the tissues that express those neuropeptides were not used in the construction of the cDNA libraries. One novel neuropeptide was identified: elongated PDH (pigment dispersing hormone), a variation on PDH that has a two-amino-acid insertion in its core sequence. Hyrg is another peptide that is ubiquitously present in decapods and is likely a novel neuropeptide precursor. Discussion. Many insect species have lost one or more neuropeptide genes, but apart from elongated PDH and hyrg all other decapod neuropeptides are present in at least some insect species, and allatotropin is the only insect neuropeptide missing from decapods. This strong similarity between insect and decapod neuropeptidomes makes it possible to predict the receptors for decapod neuropeptides that have been deorphanized in insects. This includes the androgenic insulin-like peptide that seems to be homologous to drosophila insulin-like peptide 8. PMID- 27257541 TI - SigmoID: a user-friendly tool for improving bacterial genome annotation through analysis of transcription control signals. AB - The majority of bacterial genome annotations are currently automated and based on a 'gene by gene' approach. Regulatory signals and operon structures are rarely taken into account which often results in incomplete and even incorrect gene function assignments. Here we present SigmoID, a cross-platform (OS X, Linux and Windows) open-source application aiming at simplifying the identification of transcription regulatory sites (promoters, transcription factor binding sites and terminators) in bacterial genomes and providing assistance in correcting annotations in accordance with regulatory information. SigmoID combines a user friendly graphical interface to well known command line tools with a genome browser for visualising regulatory elements in genomic context. Integrated access to online databases with regulatory information (RegPrecise and RegulonDB) and web-based search engines speeds up genome analysis and simplifies correction of genome annotation. We demonstrate some features of SigmoID by constructing a series of regulatory protein binding site profiles for two groups of bacteria: Soft Rot Enterobacteriaceae (Pectobacterium and Dickeya spp.) and Pseudomonas spp. Furthermore, we inferred over 900 transcription factor binding sites and alternative sigma factor promoters in the annotated genome of Pectobacterium atrosepticum. These regulatory signals control putative transcription units covering about 40% of the P. atrosepticum chromosome. Reviewing the annotation in cases where it didn't fit with regulatory information allowed us to correct product and gene names for over 300 loci. PMID- 27257542 TI - DICOM for quantitative imaging biomarker development: a standards based approach to sharing clinical data and structured PET/CT analysis results in head and neck cancer research. AB - Background. Imaging biomarkers hold tremendous promise for precision medicine clinical applications. Development of such biomarkers relies heavily on image post-processing tools for automated image quantitation. Their deployment in the context of clinical research necessitates interoperability with the clinical systems. Comparison with the established outcomes and evaluation tasks motivate integration of the clinical and imaging data, and the use of standardized approaches to support annotation and sharing of the analysis results and semantics. We developed the methodology and tools to support these tasks in Positron Emission Tomography and Computed Tomography (PET/CT) quantitative imaging (QI) biomarker development applied to head and neck cancer (HNC) treatment response assessment, using the Digital Imaging and Communications in Medicine (DICOM((r))) international standard and free open-source software. Methods. Quantitative analysis of PET/CT imaging data collected on patients undergoing treatment for HNC was conducted. Processing steps included Standardized Uptake Value (SUV) normalization of the images, segmentation of the tumor using manual and semi-automatic approaches, automatic segmentation of the reference regions, and extraction of the volumetric segmentation-based measurements. Suitable components of the DICOM standard were identified to model the various types of data produced by the analysis. A developer toolkit of conversion routines and an Application Programming Interface (API) were contributed and applied to create a standards-based representation of the data. Results. DICOM Real World Value Mapping, Segmentation and Structured Reporting objects were utilized for standards-compliant representation of the PET/CT QI analysis results and relevant clinical data. A number of correction proposals to the standard were developed. The open-source DICOM toolkit (DCMTK) was improved to simplify the task of DICOM encoding by introducing new API abstractions. Conversion and visualization tools utilizing this toolkit were developed. The encoded objects were validated for consistency and interoperability. The resulting dataset was deposited in the QIN-HEADNECK collection of The Cancer Imaging Archive (TCIA). Supporting tools for data analysis and DICOM conversion were made available as free open-source software. Discussion. We presented a detailed investigation of the development and application of the DICOM model, as well as the supporting open-source tools and toolkits, to accommodate representation of the research data in QI biomarker development. We demonstrated that the DICOM standard can be used to represent the types of data relevant in HNC QI biomarker development, and encode their complex relationships. The resulting annotated objects are amenable to data mining applications, and are interoperable with a variety of systems that support the DICOM standard. PMID- 27257543 TI - Evolution of parasitism and mutualism between filamentous phage M13 and Escherichia coli. AB - Background. How host-symbiont interactions coevolve between mutualism and parasitism depends on the ecology of the system and on the genetic and physiological constraints of the organisms involved. Theory often predicts that greater reliance on horizontal transmission favors increased costs of infection and may result in more virulent parasites or less beneficial mutualists. We set out to understand transitions between parasitism and mutualism by evolving the filamentous bacteriophage M13 and its host Escherichia coli. Results. The effect of phage M13 on bacterial fitness depends on the growth environment, and initial assays revealed that infected bacteria reproduce faster and to higher density than uninfected bacteria in 96-well microplates. These data suggested that M13 is, in fact, a facultative mutualist of E. coli. We then allowed E. coli and M13 to evolve in replicated environments, which varied in the relative opportunity for horizontal and vertical transmission of phage in order to assess the evolutionary stability of this mutualism. After 20 experimental passages, infected bacteria from treatments with both vertical and horizontal transmission of phage had evolved the fastest growth rates. At the same time, phage from these treatments no longer benefited the ancestral bacteria. Conclusions. These data suggest a positive correlation between the positive effects of M13 on E. coli hosts from the same culture and the negative effects of the same phage toward the ancestral bacterial genotype. The results also expose flaws in applying concepts from the virulence-transmission tradeoff hypothesis to mutualism evolution. We discuss the data in the context of more recent theory on how horizontal transmission affects mutualisms and explore how these effects influence phages encoding virulence factors in pathogenic bacteria. PMID- 27257544 TI - Stronger cortisol response to acute psychosocial stress is correlated with larger decrease in temporal sensitivity. AB - As a fundamental dimension of cognition and behavior, time perception has been found to be sensitive to stress. However, how one's time perception changes with responses to stress is still unclear. The present study aimed to investigate the relationship between stress-induced cortisol response and time perception. A group of 40 healthy young male adults performed a temporal bisection task before and after the Trier Social Stress Test for a stress condition. A control group of 27 male participants completed the same time perception task without stress induction. In the temporal bisection task, participants were first presented with short (400 ms) and long (1,600 ms) visual signals serving as anchor durations and then required to judge whether the intermediate probe durations were more similar to the short or the long anchor. The bisection point and Weber ratio were calculated and indicated the subjective duration and the temporal sensitivity, respectively. Data showed that participants in the stress group had significantly increased salivary cortisol levels, heart rates, and negative affects compared with those in the control group. The results did not show significant group differences for the subjective duration or the temporal sensitivity. However, the results showed a significant positive correlation between stress-induced cortisol responses and decreases in temporal sensitivity indexed by increases in the Weber ratio. This correlation was not observed for the control group. Changes in subjective duration indexed by temporal bisection points were not correlated with cortisol reactivity in both the groups. In conclusion, the present study found that although no significant change was observed in time perception after an acute stressor on the group-level comparison (i.e., stress vs. nonstress group), individuals with stronger cortisol responses to stress showed a larger decrease in temporal sensitivity. This finding may provide insight into the understanding of the relationship between stress and temporal sensitivity. PMID- 27257545 TI - De novo assembly and characterization of the Chinese three-keeled pond turtle (Mauremys reevesii) transcriptome: presence of longevity-related genes. AB - Mauremys reevesii (Geoemydidae) is one of the most common and widespread semi aquatic turtles in East Asia. The unusually long lifespan of some individuals makes this turtle species a potentially useful model organism for studying the molecular basis of longevity. In this study, pooled total RNA extracted from liver, spleen and skeletal-muscle of three adult individuals were sequenced using Illumina Hiseq 2500 platform. A set of telomere-related genes were found in the transcriptome, including tert, tep1, and six shelterin complex proteins coding genes (trf1, trf2, tpp1, pot1, tin2 and rap1). These genes products protect chromosome ends from deterioration and therefore significantly contribute to turtle longevity. The transcriptome data generated in this study provides a comprehensive reference for future molecular studies in the turtle. PMID- 27257546 TI - Developing demographic toxicity data: optimizing effort for predicting population outcomes. AB - Mounting evidence suggests that population endpoints in risk assessment are far more accurate than static assessments. Complete demographic toxicity data based on full life tables are eminently useful in predicting population outcomes in many applications because they capture both lethal and sublethal effects; however, developing these life tables is extremely costly. In this study we investigated the efficiency of partial life cycle tests as a substitute for full life cycles in parameterizing population models. Life table data were developed for three species of Daphniids, Ceriodaphnia dubia, Daphnia magna, and D. pulex, weekly throughout the life span of these species. Population growth rates (lambda) and a series of other demographic parameters generated from the complete life cycle were compared to those calculated from cumulative weeks of the life cycle in order to determine the minimum number of weeks needed to generate an accurate population projection. Results showed that for C. dubia and D. pulex, lambda values developed at >4 weeks (44.4% of the life cycle) were not significantly different from lambda developed for the full life cycle (9 weeks) of each species. For D. magna, lambda values developed at >7 weeks (70% of the life cycle) were not significantly different from lambda developed for the full life cycle (10 weeks). Furthermore, these cutoff points for lambda were not the same for other demographic parameters, with no clear pattern emerging. Our results indicate that for C. dubia, D. magna, and D. pulex, partial life tables can be used to generate population growth rates in lieu of full life tables. However, the implications of differences in cutoff points for different demographic parameters need to be investigated further. PMID- 27257547 TI - Retrospective study on structural neuroimaging in first-episode psychosis. AB - Background. No consensus between guidelines exists regarding neuroimaging in first-episode psychosis. The purpose of this study is to assess anomalies found in structural neuroimaging exams (brain computed tomography (CT) and magnetic resonance imaging (MRI)) in the initial medical work-up of patients presenting first-episode psychosis. Methods. The study subjects were 32 patients aged 18-48 years (mean age: 29.6 years), consecutively admitted with first-episode psychosis diagnosis. Socio-demographic and clinical data and neuroimaging exams (CT and MRI) were retrospectively studied. Diagnostic assessments were made using the Operational Criteria Checklist +. Neuroimaging images (CT and MRI) and respective reports were analysed by an experienced consultant psychiatrist. Results. None of the patients had abnormalities in neuroimaging exams responsible for psychotic symptoms. Thirty-seven percent of patients had incidental brain findings not causally related to the psychosis (brain atrophy, arachnoid cyst, asymmetric lateral ventricles, dilated lateral ventricles, plagiocephaly and falx cerebri calcification). No further medical referral was needed for any of these patients. No significant differences regarding gender, age, diagnosis, duration of untreated psychosis, in-stay and cannabis use were found between patients who had neuroimaging abnormalities versus those without. Discussion. This study suggests that structural neuroimaging exams reveal scarce abnormalities in young patients with first-episode psychosis. Structural neuroimaging is especially useful in first-episode psychosis patients with neurological symptoms, atypical clinical picture and old age. PMID- 27257548 TI - Sex expression and floral diversity in Jatropha curcas: a population study in its center of origin. AB - Sex expression and floral morphology studies are central to understand breeding behavior and to define the productive potential of plant genotypes. In particular, the new bioenergy crop Jatropha curcas L. has been classified as a monoecious species. Nonetheless, there is no information about its reproductive diversity in the Mesoamerican region, which is considered its center of origin and diversification. Thus, we determined sex expression and floral morphology in J. curcas populations from southern Mexico and Guatemala. Our results showed that most of J. curcas specimens had typical inflorescences with separate sexes (monoecious); meanwhile, the rest were atypical (gynoecious, androecious, andromonoecious, androgynomonoecious). The most important variables to group these populations, based on a discriminant analysis, were: male flower diameter, female petal length and male nectary length. From southern Mexico "Guerrero" was the most diverse population, and "Centro" had the highest variability among the populations from Chiapas. A cluster analysis showed that the accessions from southern Mexico were grouped without showing any correlation with the geographical origin, while those accessions with atypical sexuality were grouped together. To answer the question of how informative are floral morphological traits compared to molecular markers, we perform a Mantel correlation test between the distance matrix generated in this study and the genetic distance matrix (AFLP) previously reported for the same accessions. We found significant correlation between data at the level of accessions. Our results contribute to design genetic improvement programs by using sexually and morphologically contrasting plants from the center of origin. PMID- 27257549 TI - Ecological implications of metabolic compensation at low temperatures in salamanders. AB - Global warming is influencing the biology of the world's biota. Temperature increases are occurring at a faster pace than that experienced by organisms in their evolutionary histories, limiting the organisms' response to new conditions. Mechanistic models that include physiological traits can help predict species' responses to warming. Changes in metabolism at high temperatures are often examined; yet many species are behaviorally shielded from high temperatures. Salamanders generally favor cold temperatures and are one of few groups of metazoans to be most species-rich in temperate regions. I examined variation in body temperature, behavioral activity, and temperature dependence of resting heart rate, used as a proxy for standard metabolic rate, in fire salamanders (Salamandra salamandra). Over 26 years, I found that salamanders are behaviorally active at temperatures as low as 1 degrees C, and aestivate at temperatures above 16 degrees C. Infrared thermography indicates limited thermoregulation opportunities for these nocturnal amphibians. Temperature affects resting heart rate, causing metabolic depression above 11 degrees C, and metabolic compensation below 8 degrees C: heart rate at 3 degrees C is 224% the expected heart rate. Thus, salamanders operating at low temperatures during periods of peak behavioral activity are able to maintain a higher metabolic rate than the rate expected in absence of compensation. This compensatory mechanism has important ecological implications, because it increases estimated seasonal heart rates. Increased heart rate, and thus metabolism, will require higher caloric intake for field-active salamanders. Thus, it is important to consider a species performance breadth over the entire temperature range, and particularly low temperatures that are ecologically relevant for cold tolerant species such as salamanders. PMID- 27257550 TI - DeepSNVMiner: a sequence analysis tool to detect emergent, rare mutations in subsets of cell populations. AB - Background. Massively parallel sequencing technology is being used to sequence highly diverse populations of DNA such as that derived from heterogeneous cell mixtures containing both wild-type and disease-related states. At the core of such molecule tagging techniques is the tagging and identification of sequence reads derived from individual input DNA molecules, which must be first computationally disambiguated to generate read groups sharing common sequence tags, with each read group representing a single input DNA molecule. This disambiguation typically generates huge numbers of reads groups, each of which requires additional variant detection analysis steps to be run specific to each read group, thus representing a significant computational challenge. While sequencing technologies for producing these data are approaching maturity, the lack of available computational tools for analysing such heterogeneous sequence data represents an obstacle to the widespread adoption of this technology. Results. Using synthetic data we successfully detect unique variants at dilution levels of 1 in a 1,000,000 molecules, and find DeeepSNVMiner obtains significantly lower false positive and false negative rates compared to popular variant callers GATK, SAMTools, FreeBayes and LoFreq, particularly as the variant concentration levels decrease. In a dilution series with genomic DNA from two cells lines, we find DeepSNVMiner identifies a known somatic variant when present at concentrations of only 1 in 1,000 molecules in the input material, the lowest concentration amongst all variant callers tested. Conclusions. Here we present DeepSNVMiner; a tool to disambiguate tagged sequence groups and robustly identify sequence variants specific to subsets of starting DNA molecules that may indicate the presence of a disease. DeepSNVMiner is an automated workflow of custom sequence analysis utilities and open source tools able to differentiate somatic DNA variants from artefactual sequence variants that likely arose during DNA amplification. The workflow remains flexible such that it may be customised to variants of the data production protocol used, and supports reproducible analysis through detailed logging and reporting of results. DeepSNVMiner is available for academic non-commercial research purposes at https://github.com/mattmattmattmatt/DeepSNVMiner. PMID- 27257551 TI - Postcranial anatomy of Pissarrachampsa sera (Crocodyliformes, Baurusuchidae) from the Late Cretaceous of Brazil: insights on lifestyle and phylogenetic significance. AB - The postcranial anatomy of Crocodyliformes has historically been neglected, as most descriptions are based solely on skulls. Yet, the significance of the postcranium in crocodyliforms evolution is reflected in the great lifestyle diversity exhibited by the group, with members ranging from terrestrial animals to semi-aquatic and fully marine forms. Recently, studies have emphasized the importance of the postcranium. Following this trend, here we present a detailed description of the postcranial elements of Pissarrachampsa sera (Mesoeucrocodylia, Baurusuchidae), from the Adamantina Formation (Bauru Group, Late Cretaceous of Brazil). The preserved elements include dorsal vertebrae, partial forelimb, pelvic girdle, and hindlimbs. Comparisons with the postcranial anatomy of baurusuchids and other crocodyliforms, together with body-size and mass estimates, lead to a better understanding of the paleobiology of Pissarrachampsa sera, including its terrestrial lifestyle and its role as a top predator. Furthermore, the complete absence of osteoderms in P. sera, a condition previously known only in marine crocodyliforms, suggests osteoderms very likely played a minor role in locomotion of baurusuchids, unlike other groups of terrestrial crocodyliforms. Finally, a phylogenetic analysis including the newly recognized postcranial features was carried out, and exploratory analyses were performed to investigate the influence of both cranial and postcranial characters in the phylogeny of Crocodyliformes. Our results suggest that crocodyliform relationships are mainly determined by cranial characters. However, this seems to be a consequence of the great number of missing entries in the data set with only postcranial characters and not of the lack of potential (or synapomorphies) for this kind of data to reflect the evolutionary history of Crocodyliformes. PMID- 27257552 TI - Sperm removal during copulation confirmed in the oldest extant damselfly, Hemiphlebia mirabilis. AB - Postcopulatory sexual selection may favour mechanisms to reduce sperm competition, like physical sperm removal by males. To investigate the origin of sperm removal, I studied the reproductive behaviour and mechanisms of sperm competition in the only living member of the oldest damselfly family, Hemiphlebia mirabilis, one species that was considered extinct in the 1980s. This species displays scramble competition behaviour. Males search for females with short flights and both sexes exhibit a conspicuous "abdominal flicking". This behaviour is used by males during an elaborate precopulatory courtship, unique among Odonata. Females use a similar display to reject male attempts to form tandem, but eventually signal receptivity by a particular body position. Males immobilise females during courtship using their legs, which, contrarily to other damselflies, never autotomise. Copulation is short (range 4.1-18.7 min), and occurs in two sequential stages. In the first stage, males remove part of the stored sperm, and inseminate during the second stage, at the end of mating. The male genital ligula matches the size and form of female genitalia, and ends by two horns covered by back-oriented spines. The volume of sperm in females before copulation was 2.7 times larger than the volume stored in females whose copulation was interrupted at the end of stage I, indicative of a significant sperm removal. These results point out that sperm removal is an old character in the evolution of odonates, possibly dating back to the Permian. PMID- 27257553 TI - Strategies for improved rhamnolipid production by Pseudomonas aeruginosa PA1. AB - Rhamnolipids are biosurfactants with potential for diversified industrial and environmental uses. The present study evaluated three strategies for increasing the production of rhamnolipid-type biosurfactants produced by Pseudomonas aeruginosa strain PA1. The influence of pH, the addition of P. aeruginosa spent culture medium and the use of a fed-batch process were examined. The culture medium adjusted to pH 7.0 was the most productive. Furthermore, the pH of the culture medium had a measurable effect on the ratio of synthesized mono- and dirhamnolipids. At pH values below 7.3, the proportion of monorhamnolipids decreased from 45 to 24%. The recycling of 20% of the spent culture medium in where P. aeruginosa was grown up to the later stationary phase was responsible for a 100% increase in rhamnolipid volumetric productivity in the new culture medium. Finally, the use of fed-batch operation under conditions of limited nitrogen resulted in a 3.8-fold increase in the amount of rhamnolipids produced (2.9 g L(-1)-10.9 g L(-1)). These results offer promising pathways for the optimization of processes for the production of rhamnolipids. PMID- 27257554 TI - Bioinformatics analysis of the structural and evolutionary characteristics for toll-like receptor 15. AB - Toll-like receptors (TLRs) play important role in the innate immune system. TLR15 is reported to have a unique role in defense against pathogens, but its structural and evolution characterizations are still poorly understood. In this study, we identified 57 completed TLR15 genes from avian and reptilian genomes. TLR15 clustered into an individual clade and was closely related to family 1 on the phylogenetic tree. Unlike the TLRs in family 1 with the broken asparagine ladders in the middle, TLR15 ectodomain had an intact asparagine ladder that is critical to maintain the overall shape of ectodomain. The conservation analysis found that TLR15 ectodomain had a highly evolutionarily conserved region on the convex surface of LRR11 module, which is probably involved in TLR15 activation process. Furthermore, the protein-protein docking analysis indicated that TLR15 TIR domains have the potential to form homodimers, the predicted interaction interface of TIR dimer was formed mainly by residues from the BB-loops and alphaC helixes. Although TLR15 mainly underwent purifying selection, we detected 27 sites under positive selection for TLR15, 24 of which are located on its ectodomain. Our observations suggest the structural features of TLR15 which may be relevant to its function, but which requires further experimental validation. PMID- 27257555 TI - Temporal regulation of proteome profile in the fruit fly, Drosophila melanogaster. AB - Background. Diurnal rhythms of protein synthesis controlled by the biological clock underlie the rhythmic physiology in the fruit fly, Drosophila melanogaster. In this study, we conducted a proteome-wide investigation of rhythmic protein accumulation in D. melanogaster. Materials and Methods. Total protein collected from fly samples harvested at 4 h intervals over the 24 h period were subjected to two-dimensional gel electrophoresis, trypsin digestion and MS/MS analysis. Protein spots/clusters were identified with MASCOT search engine and Swiss-Prot database. Expression of proteins was documented as percentage of volume contribution using the Image Master 2D Platinum software. Results. A total of 124 protein spots/clusters were identified using MS/MS analysis. Significant variation in the expression of 88 proteins over the 24-h period was observed. A relatively higher number of proteins was upregulated during the night compared to the daytime. The complexity of temporal regulation of the D. melanogaster proteome was further reflected from functional annotations of the differently expressed proteins, with those that were upregulated at night being restricted to the heat shock proteins and proteins involved in metabolism, muscle activity, protein synthesis/folding/degradation and apoptosis, whilst those that were overexpressed in the daytime were apparently involved in metabolism, muscle activity, ion-channel/cellular transport, protein synthesis/folding/degradation, redox homeostasis, development and transcription. Conclusion. Our data suggests that a wide range of proteins synthesized by the fruit fly, D. melanogaster, is under the regulation of the biological clock. PMID- 27257557 TI - Proficient brain for optimal performance: the MAP model perspective. AB - Background. The main goal of the present study was to explore theta and alpha event-related desynchronization/synchronization (ERD/ERS) activity during shooting performance. We adopted the idiosyncratic framework of the multi-action plan (MAP) model to investigate different processing modes underpinning four types of performance. In particular, we were interested in examining the neural activity associated with optimal-automated (Type 1) and optimal-controlled (Type 2) performances. Methods. Ten elite shooters (6 male and 4 female) with extensive international experience participated in the study. ERD/ERS analysis was used to investigate cortical dynamics during performance. A 4 * 3 (performance types * time) repeated measures analysis of variance was performed to test the differences among the four types of performance during the three seconds preceding the shots for theta, low alpha, and high alpha frequency bands. The dependent variables were the ERD/ERS percentages in each frequency band (i.e., theta, low alpha, high alpha) for each electrode site across the scalp. This analysis was conducted on 120 shots for each participant in three different frequency bands and the individual data were then averaged. Results. We found ERS to be mainly associated with optimal-automatic performance, in agreement with the "neural efficiency hypothesis." We also observed more ERD as related to optimal controlled performance in conditions of "neural adaptability" and proficient use of cortical resources. Discussion. These findings are congruent with the MAP conceptualization of four performance states, in which unique psychophysiological states underlie distinct performance-related experiences. From an applied point of view, our findings suggest that the MAP model can be used as a framework to develop performance enhancement strategies based on cognitive and neurofeedback techniques. PMID- 27257556 TI - ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice. AB - Cannabidiol (CBD) is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (Bcrp) mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB) and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT) mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b (-/-)), Bcrp knockout (Abcg2 (-/-)), combined P-gp/Bcrp knockout (Abcb1a/b (-/-) Abcg2 (-/-)) and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders. PMID- 27257558 TI - The frequency of the m.1555A>G (MTRNR1) variant in UK patients with suspected mitochondrial deafness. PMID- 27257559 TI - Erratum: Locally Advanced Breast Cancer: Autologous Versus Implant-based Reconstruction: Erratum. AB - [This corrects the article DOI: 10.1097/GOX.0000000000000598.]. PMID- 27257560 TI - The Significance of Rectus Femoris for the Favorable Functional Outcome After Total Femur Replacement. AB - BACKGROUND: In treatment of tumors, we usually reconstruct after resection of the entire femur using only metallic modular endoprostheses among many procedures and defined it as a total femur replacement. We studied the interrelation between the preservation of rectus femoris and the functional outcome after total femur replacement. METHODS: We rated the functional outcomes of 21 patients who underwent total femur replacement. We categorized the subjects into 2 groups: group A (rectus femoris preserved) and group B (rectus femoris unpreserved). We examined them based on the Mann-Whitney U test between the 2 groups in average through the Musculoskeletal Tumor Society functional scores. RESULTS: The average score of group A was 20 of 25 (11-25; 80%), whereas the average score of group B was 10 of 25 (4-13; 40%). There was significant difference between the groups (P = 0.00168877). CONCLUSION: We found that the preservation of rectus femoris is imperative for achieving the favorable functional outcome in total femur replacement. PMID- 27257562 TI - Microvascular Reconstruction of Free Jejunal Graft in Larynx-preserving Esophagectomy for Cervical Esophageal Carcinoma. AB - BACKGROUND: Losing the ability to speak severely affects the quality of life, and patients who have undergone laryngectomy tend to become depressed, which may lead to social withdrawal. Recently, with advancements in chemoradiotherapy and with alternative perspectives on postoperative quality of life, larynx preservation has been pursued; however, the selection of candidates and the optimal reconstructive procedure remain controversial. In this study, we retrospectively reviewed our experience with free jejunal graft for larynx-preserving cervical esophagectomy (LPCE), focusing on microvascular reconstruction. METHODS: Seven patients underwent LPCE for cervical esophageal carcinoma, and defects were reconstructed by free jejunal transfer subsequently. We collected preoperative and postoperative data of the patients and assessed the importance of the procedure. RESULTS: We mostly used the transverse cervical artery as the recipient, and a longer operative time was required, particularly for the regrowth cases. The operative field for microvascular anastomosis was more limited and deeper than those in the laryngectomy cases. Two graft necrosis cases were confirmed at postoperative day 9 or 15, and vessels contralateral from the graft were chosen as recipients in both patients. CONCLUSIONS: Microvascular reconstruction for free jejunal graft in LPCE differed in several ways from the procedure combined with laryngectomy. Compression from the tracheal cartilage to the pedicle was suspected as the reason of the necrosis clinically and pathologically. Therefore, we should select recipient vessels from the ipsilateral side of the graft, and careful and extended monitoring of the flap should be considered to make this procedure successful. PMID- 27257561 TI - Stromal Vascular Fraction Combined with Shock Wave for the Treatment of Peyronie's Disease. AB - BACKGROUND: This pilot study was used to evaluate safety and subjective outcomes in a small series of Peyronie's disease patients using a combination of autologous stromal vascular fraction (SVF) and penile shock wave treatments. SVF can be procured and deployed into Peyronie's plaques, enabling the surgeons to procure and mobilize significant numbers of both adult mesenchymal stem cells and antiinflammatory cytokines released from the adipose collagen matrix after collagen digestion. Penile shock wave therapy stimulates targeted tissues and may activate stem cells found in the SVF and promote healing and fibrosis mitigation. METHODS: SVF isolated from lipoaspirate was deployed by injection into 11 patients with Peyronie's plaques in combination with a series of shock wave treatments. Subjective outcomes tests performed at baseline and at 6 months included the Erectile Hardness Grading Score and the Peyronie's Disease Questionnaire (Questions 1-6). RESULTS: All patients noted subjective improvement in curvature and subjective reduction in plaque size. Seven patients reported improvement in erectile function. Mean Erectile Hardness Grading Score increased from 2.7 to 3.5, and mean Peyronie's Disease Questionnaire scores decreased from 15.0 to 8.7. CONCLUSIONS: SVF is known to have scar mitigation, antiinflammatory, immunomodulatory, and regenerative effects, and it has been used for a variety of conditions on an investigational basis. SVF containing mesenchymal stem cells can be procured in a closed surgical system from lipoaspirate in a same-day setting and deployed directly into Peyronie's plaques in combination with penile shock wave therapy resulting in plaque mitigation. PMID- 27257563 TI - Nested Graft for Acral Lichen Sclerosus of the Feet: A Surgical Treatment for an Inflammatory Disease. AB - The "nested graft" is an innovative and well-defined surgical technique used for chronic wound healing that induces the de-senescence of fibroblasts in the wound bed. We report a case of a 76-year-old man affected by plantar chronic wounds because of acral lichen sclerosus and atrophicus localized at both feet and treated for many years successfully with immunosuppressive agents. For cardiological dysfunction, systemic therapy was reduced to low dosage of steroids with an increase of ulcerations (5 * 2 cm). So we decided to perform the nested graft on the plantar region. After the surgical procedure, all the grafted ulcers healed, and at a 4-month follow-up, no signs of lichen sclerosus were present. PMID- 27257564 TI - Inframammary Fold Reconstruction: A Biomechanical Analysis. AB - BACKGROUND: Inframammary fold reconstruction has scarcely been evaluated in literature. No biomechanical analyses have been performed comparing different reconstructive methods. This evaluation compares the gold-standard suture reconstruction with an intrarib anchor system (Micro BioComposite SutureTak, Arthrex). METHODS: Three analysis groups were compared including 8 Sawbone blocks, 22 embalmed cadaver, and 27 regular cadaver specimens (N = 57). Transient mechanical analysis was performed at 5 N/s using an Instron 5565 test frame. RESULTS: Ultimate load favored the anchor system (compared with the gold-standard suture) by a factor of 9.8 (P < 0.0001) for the regular cadaver group and a factor of 1.7 (P < 0.038) for the embalmed cadaver group. A similar statistically significant benefit was shown for stiffness and load at 2-mm displacement. CONCLUSIONS: This analysis showed an anchor system to be the biomechanically superior fixation method in terms of ultimate load, fixation stiffness, and displacement at failure when compared with the gold-standard suture method in inframammary fold reconstruction. Because of superior stability in every aspect, an anchor system may be considered for inframammary fold reconstruction. PMID- 27257565 TI - Bilateral Distraction Osteogenesis of Vascularized Iliac Crest Free Flaps Used in Mandibular Reconstruction. AB - Vascularized free flaps have become the gold standard in reconstructing large segmental mandibular defects; however, even when bony union and soft-tissue coverage is achieved, insufficient bone stock and altered facial contour can create functional and cosmetic problems for the patient. There have been limited case reports on the use of secondary distraction osteogenesis to address these issues. The authors report a case of bilateral mandibular distraction of deep circumflex iliac artery free flaps, used for mandibular reconstruction after total mandibulectomy for treatment of osteosarcoma. Performed for reasons of retrognathia and facilitation of dental prosthetic rehabilitation, this is the first case of bilateral horizontal distraction osteogenesis of deep circumflex iliac artery free flaps reported in the literature. PMID- 27257566 TI - Relationship between BMI and Postoperative Complications with Free Flap in Anterolateral Craniofacial Reconstruction. AB - BACKGROUND: Although we have seen tremendous advancement in microsurgery over the last 2 decades and free tissue transfer has become standard for head and neck reconstruction, surgeons still struggle to prevent postoperative complications. We examined the relationship between body mass index (BMI) and postoperative complications in patients undergoing rectus abdominis free flap transfer after anterolateral craniofacial resection. METHODS: This was a retrospective review of reconstructive surgery using rectus abdominis musculocutaneous free flap in patients with locally advanced maxillary sinus carcinoma from 2003 to 2014 (n = 35, 27 men and 8 women; average age, 60.9 +/- 7.8 years). All patients underwent craniofacial reconstruction after anterior and middle cranial fossa skull base resection and maxillectomy (class IV, subtype a) with palatal resection. Patients were categorized based on sex, BMI, and other parameters. RESULTS: Recipient-site infection occurred in 11 patients (31.4%), cerebrospinal fluid leakage in 6 (17.1%), partial flap necrosis in 2 (5.7%), total flap necrosis in 1 (2.9%), and facial fistula in 4 (11.4%). Women showed partial flap necrosis significantly more frequently (P = 0.047), probably owing to poor vascular supply of the subcutaneous fat layer. Patients with low BMI (<20 kg/m(2)) showed recipient-site infection (P = 0.02) and facial fistula (P = 0.01) significantly more frequently owing to insufficient tissue volume and poor vascular supply. CONCLUSION: Postoperative recipient-site infection and facial fistula occurred mainly in low BMI patients. Surgeons should take care to achieve sufficient donor tissue on low BMI patients. Using a prosthetic obturator in low-BMI patients for craniofacial reconstruction can be a good alternative option to reduce postoperative complications due to insufficient donor tissue volume. PMID- 27257567 TI - Treatment of Peripheral Neuropathy in Leprosy: The Case for Nerve Decompression. AB - Plastic surgery has a tradition of caring for patients with facial deformity and hand deformity related to leprosy. The approach, however, to the progressive deformity and disability related to chronic nerve compression is underappreciated in the world today. A cohort of patients with leprous neuropathy from an indigenous area of leprosy in Ecuador was evaluated for the presence of chronic peripheral nerve compression, and 12 patients were chosen for simultaneous upper and lower extremity, unilateral, nerve decompression at multiple levels along the course of each nerve. The results at 1 year of follow-up show that 6 patients improved into the excellent category and 4 patients improved into the good category for improved function. Based on the early results in this small cohort of patients with leprous neuropathy, an approach to peripheral nerve decompression, encompassing the concept of multiple crush at multiple levels of each nerve, seems to offer optimism to improve upper and lower extremity limb function. Long-term studies with quality-of-life outcomes would be welcome. PMID- 27257568 TI - A Twelve-Year Consecutive Case Experience in Thoracic Reconstruction. AB - BACKGROUND: We describe the second largest contemporary series of flaps used in thoracic reconstruction. METHODS: A retrospective review of patients undergoing thoracomyoplasty from 2001 to 2013 was conducted. Ninety-one consecutive patients were identified. RESULTS: Thoracomyoplasty was performed for 67 patients with intrathoracic indications and 24 patients with chest wall defects. Malignancy and infection were the most common indications for reconstruction (P < 0.01). The latissimus dorsi (LD), pectoralis major, and serratus anterior muscle flaps remained the workhorses of reconstruction (LD and pectoralis major: 64% flaps in chest wall reconstruction; LD and serratus anterior: 85% of flaps in intrathoracic indication). Only 12% of patients required mesh. Only 6% of patients with <2 ribs resected required mesh when compared with 24% with 3-4 ribs, and 100% with 5 or more ribs resected (P < 0.01). Increased rib resections required in chest wall reconstruction resulted in a longer hospital stay (P < 0.01). Total comorbidities and complications were related to length of stay only in intrathoracic indication (P < 0.01). Average intubation time was significantly higher in patients undergoing intrathoracic indication (5.51 days) than chest wall reconstruction (0.04 days), P < 0.05. Average hospital stay was significantly higher in patients undergoing intrathoracic indication (23 days) than chest wall reconstruction (12 days), P < 0.05. One-year survival was most poor for intrathoracic indication (59%) versus chest wall reconstruction (83%), P = 0.0048. CONCLUSION: Thoracic reconstruction remains a safe and successful intervention that reliably treats complex and challenging problems, allowing more complex thoracic surgery problems to be salvaged. PMID- 27257569 TI - Anatomic and Compression Topography of the Lesser Occipital Nerve. AB - BACKGROUND: The surgical treatment of occipital headaches focuses on the greater, lesser, and third occipital nerves. The lesser occipital nerve (LON) is usually transected with relatively limited available information regarding the compression topography thereof and how such knowledge may impact surgical treatment. METHODS: Eight fresh frozen cadavers were dissected focusing on the LON in relation to 3 clinically relevant compression zones. The x axis was a line drawn through the occipital protuberance (OP) and the y axis, the posterior midline (PM). In addition, a prospectively collected cohort of 36 patients who underwent decompression of the LON is presented with their clinical results, including migraine headache index scores. RESULTS: The LON was found in compression zone 1, with a mean of 7.8 cm caudal to the OP and 6.3 cm lateral to the PM. The LON was found at the midpoint of compression zone 2, with an average of 5.5 cm caudal to the OP and 6.2 cm lateral to the PM. At compression zone 3, the medial-most LON branch was located approximately 1 cm caudal to the OP and 5.35 cm lateral to the PM, whereas the lateral-most branch was identified 1 cm caudal to the OP and 6.5 cm lateral to the PM. Of the 36 decompression patients analyzed, only 5 (14%) required neurectomy as the remainder achieved statistically significant improvements in migraine headache index scores postoperatively. CONCLUSION: The knowledge of LON anatomy can aid in nerve dissection and preservation, thereby leading to successful outcomes without requiring neurectomy. PMID- 27257570 TI - Breast Capsular Cerebrospinal Fluid Collection from Migration of a Ventriculoperitoneal Shunt Catheter. AB - In this case report we have described an unusual complication of ventriculoperitoneal shunt migration into a breast implant capsule. The patient was appropriately diagnosed with computed tomographic imaging and successfully managed with shunt revision and cerebrospinal fluid aspiration. Given the high complication profile of ventriculoperitoneal shunt catheters, this case suggests an opportunity for improved perioperative communication between plastic surgeons and neurosurgeons in patients with breast implants. Coordination regarding the subcutaneous catheter tunneling may hopefully minimize the risk of this complication. PMID- 27257571 TI - Plastic Surgery Training Worldwide: Part 1. The United States and Europe. AB - BACKGROUND: Major differences exist in residency training, and the structure and quality of residency programs differ between different countries and teaching centers. It is of vital importance that a better understanding of the similarities and differences in plastic surgery training be ascertained as a means of initiating constructive discussion and commentary among training programs worldwide. In this study, the authors provide an overview of plastic surgery training in the United States and Europe. METHODS: A survey was sent to select surgeons in 10 European countries that were deemed to be regular contributors to the plastic surgery literature. The questions focused on pathway to plastic surgery residency, length of training, required pretraining experience, training scheme, research opportunities, and examinations during and after plastic surgery residency. RESULTS: Plastic surgery residency training programs in the United States differ from the various (selected) countries in Europe and are described in detail. CONCLUSIONS: Plastic surgery education is vastly different between the United States and Europe, and even within Europe, training programs remain heterogeneous. Standardization of curricula across the different countries would improve the interaction of different centers and facilitate the exchange of vital information for quality control and future improvements. The unique characteristics of the various training programs potentially provide a basis from which to learn and to gain from one another. PMID- 27257572 TI - Use of Lumbar Perforator Recipient Vessels for Salvage Chest Wall Reconstruction: A Case Report. AB - Abdominal-based free flaps are commonly used for breast reconstruction, and the internal mammary or thoracodorsal vessels are typically used as recipient sites. Conversely, free tissue transfer is less commonly used for chest wall reconstruction in the setting of chest wall recurrence, in part, because of a paucity of recipient vessels. Here, we describe a case of a 68-year-old female smoker with metastatic breast cancer, who presented with a chest wall recurrence. There was a large area of chronic ulceration with foul smelling drainage, in addition to radiation-induced tissue injury, and palliative resection was performed. The area was reconstructed with a free transverse rectus abdominis myocutaneous flap using lumbar perforators as recipient vessels, because conventional recipient sites were unavailable because of scarring from radiation and residual tumor. This case demonstrates that uncommon recipient vessels such as lumbar perforators may allow for successful palliative chest wall reconstruction. We hypothesize that the tumor burden, previous surgeries, and radiation may have rendered the recipient field relatively ischemic, thereby inducing hypertrophy of the lumbar perforators, similar to a delay phenomenon. PMID- 27257573 TI - Release and Reconstruction of a Postburn Deformed Breast in a Young Woman. AB - Burn injuries to the anterior chest wall in the young woman may cause disfiguration or lack of development of the breasts during puberty. Often the patients are referred after puberty with an apparent lack of breast development due to firm postburn scar tissue constricting the anterior chest wall. We report a case where a young female with a postburn disfiguration and apparent diminished breast development was reconstructed successfully with incision only through the restricting burn scar, a periareolar skin excision and split-thickness skin grafting of the subsequent outburst of constricted breast tissue. PMID- 27257574 TI - Postaugmentation Galactocele Without Periareolar Incision and 8 Years After Pregnancy. PMID- 27257575 TI - Surgical Treatment of Rare Sclerosing Polycystic Adenosis of the Deep Parotid Gland. AB - We experienced a rare case of sclerosing polycystic adenosis (SPA) arising in a parotid gland. A 33-year-old man who underwent unspecified surgery for a lesion in the left parotid gland 23 years ago presented with a lesion on the same site. Computed tomography scan revealed an encapsulated 3 * 2 cm lesion. Intraoperative findings showed that the tumor was embedded deep in the parotid gland. Marginal tumor excision was performed to preserve the facial nerve. Histopathological and immunohistochemical findings led to the final diagnosis of SPA. The surgery was not associated with any other complications. To date, 28 months after surgery, recurrence has not been observed. The treatment protocol of SPA has not yet been established. To make plastic surgeons familiar with this disease, we describe this case, which was successfully treated without any complications. PMID- 27257576 TI - A Novel Technique of Intraoperative Lateral Pectoral Nerve Block During Subpectoral Breast Implant Placement. AB - Breast surgery is one of the most frequently performed surgeries in hospitals and can be associated with significant postoperative pain. We report a novel technique of intraoperative lateral pectoral nerve block under direct vision for analgesia post subpectoral implant placement for breast reconstruction. PMID- 27257577 TI - Revision Breast Augmentation at the Time of Cardiac Sarcoma Resection: The Importance of Pocket Control When Inframammary Approach Is Combined with Simultaneous Sternotomy. AB - Sternotomy in patients with previous breast augmentation becomes an aesthetic challenge when an inframammary approach is utilized over the traditional midline skin incision. Although the inframammary fold approach offers a well-concealed scar when compared with the midline chest incision, patients with a history of previous breast augmentation are at risk for alteration of the anatomy leading to symmastia, implant malposition, and asymmetry. We present a case report of sternotomy and resection of a mediastinal perivascular epithelioid cell tumor with concomitant revision augmentation with silicone implants and SERI Scaffold. Our patient had an uncomplicated postoperative course and a good cosmetic result 1 year after concomitant revision augmentation in conjunction with cardiac tumor resection. In conclusion, the authors feel that despite the difficulties in performing breast augmentation in patients undergoing thoracic surgery, it is possible to obtain good results. It is necessary to reinforce the repair with a mesh to recreate support and proper anatomy. PMID- 27257578 TI - Diagnosis of Ulnar Nerve Entrapment at the Arcade of Struthers with Electromyography and Ultrasound. AB - Ulnar neuropathy is caused by compression of the ulnar nerve in the upper extremity, frequently occurring at the level of the elbow or wrist. Rarely, ulnar nerve entrapment may be seen proximal to the elbow. This report details a case of ulnar neuropathy diagnosed and localized to the arcade of Struthers with electromyography (EMG) and ultrasound (US) imaging and confirmed at time of operative release. US imaging and EMG findings were used to preoperatively localize the level of compression in a patient presenting with left ulnar neuropathy. In this case, ulnar entrapment 8 cm proximal to the medial epicondyle was diagnosed. Surgical release was performed and verified the level of entrapment at the arcade of Struthers in the upper arm. Alleviation of symptoms was noted at 8-week follow-up; no complications occurred. US imaging can be used in complement with EMG studies to properly diagnose and localize the level of ulnar nerve entrapment. This facilitates full release of the nerve and may prevent the need for revision surgery. PMID- 27257579 TI - Body Contouring Surgery: Our 5 Years Experience. PMID- 27257580 TI - The Assessment of Thromboembolism Risk in Postbariatric Patient: Our Experience in 936 Patients. PMID- 27257581 TI - Pressure Ulcers in Patients with Spinal Cord Injuries: Concordance Between Swab and Intraoperative Culture. PMID- 27257582 TI - The New Transverse-Facial Artery Musculomucosal Flap for Intraoral Reconstructions. PMID- 27257583 TI - Surgical Treatment of Frontal and Occipital Migraines: A Comparison of Results. PMID- 27257584 TI - Assisted Healing-Selective Delayed Reconstruction for Subacute Traumatic Wounds of the Lower Limb. PMID- 27257585 TI - Lower Urinary Tract Symptoms in Male-to-Female Transsexuals: Short Terms Results and Proposal of a New Questionnaire. PMID- 27257586 TI - Arterial Pressure Management in a Reconstructive Microsurgery Patients by Dopamine Infusion in a Nonintensive Care Ward. PMID- 27257587 TI - Perineal Flap Reconstruction after Oncologic Resection. PMID- 27257588 TI - Management of the Exposed and/or Infected Breast Prosthesis: A Proposal for a Standardized Approach. PMID- 27257589 TI - Bone Quality at the Sites of Loosened Screws in Mandibular Reconstruction Plates. PMID- 27257590 TI - Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients. AB - BACKGROUND: Autologous adipose tissue injection is used in plastic surgery for correction of localized tissue atrophy and has also been successfully offered for treatment of localized scleroderma. We aimed to evaluate whether patients with systemic sclerosis (SSc) and facial handicap could also benefit from this therapy. METHODS: We included 14 patients (mean age of 53.8 +/- 9.6 years) suffering from SSc with facial handicap defined by Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20, a Rodnan skin score on the face more than or equal to 1, and maximal mouth opening of less than 55 mm. Autologous adipose tissue injection was performed under local anesthesia using the technique of subcutaneous microinjection. The main objective of this study was an improvement of the MHISS score 6 months after the surgical treatment. RESULTS: The procedure was well tolerated. We observed a mean decrease in the MHISS score of 10.7 points (+/-5.1; P < 0.0001) at 6 months (35% improvement). Secondary efficacy parameters assessing perioral skin sclerosis, maximum mouth opening, sicca syndrome, and facial pain significantly improved at 3 and 6 months postsurgery. At a 6-month follow-up, 75% of patients were satisfied or very satisfied of the adipose tissue microinjection therapy. CONCLUSIONS: Our study suggests that subcutaneous perioral microfat injection in patients with SSc is beneficial in the treatment of facial handicap, skin sclerosis, mouth opening limitation, sicca syndrome, and facial pain. Thus, this minimally invasive approach offers a new hope for face therapy for patients with SSc. PMID- 27257591 TI - The Versatile Modiolus Perforator Flap. AB - BACKGROUND: Perforator flaps are well established, and their usefulness as freestyle island flaps is recognized. The whereabouts of vascular perforators and classification of perforator flaps in the face are a debated subject, despite several anatomical studies showing similar consistency. In our experience using freestyle facial perforator flaps, we have located areas where perforators are consistently found. This study is focused on a particular perforator lateral to the angle of the mouth; the modiolus and the versatile modiolus perforator flap. METHODS: A cohort case series of 14 modiolus perforator flap reconstructions in 14 patients and a color Doppler ultrasonography localization of the modiolus perforator in 10 volunteers. RESULTS: All 14 flaps were successfully used to reconstruct the defects involved, and the location of the perforator was at the level of the modiolus as predicted. The color Doppler ultrasonography study detected a sizeable perforator at the level of the modiolus lateral to the angle of the mouth within a radius of 1 cm. This confirms the anatomical findings of previous authors and indicates that the modiolus perforator is a consistent anatomical finding, and flaps based on it can be recommended for several indications from the reconstruction of defects in the perioral area, cheek and nose. CONCLUSIONS: The modiolus is a well-described anatomical area containing a sizeable perforator that is consistently present and readily visualized using color Doppler ultrasonography. We have used the modiolus perforator flap successfully for several indications, and it is our first choice for perioral reconstruction. PMID- 27257592 TI - A Breast Foreign Body Migrating to the Back. PMID- 27257593 TI - Biological Spare Part Surgery Applied to Nasal Reconstruction. PMID- 27257594 TI - Snoopy Breast and Double Bubble Have Much in Common. PMID- 27257595 TI - Effect of Artificial Nerve Conduit Vascularization on Peripheral Nerve in a Necrotic Bed. AB - BACKGROUND: Several types of artificial nerve conduit have been used for bridging peripheral nerve gaps as an alternative to autologous nerves. However, their efficacy in repairing nerve injuries accompanied by surrounding tissue damage remains unclear. We fabricated a novel nerve conduit vascularized by superficial inferior epigastric (SIE) vessels and evaluated whether it could promote axonal regeneration in a necrotic bed. METHODS: A 15-mm nerve conduit was implanted beneath the SIE vessels in the groin of a rat to supply it with blood vessels 2 weeks before nerve reconstruction. We removed a 13-mm segment of the sciatic nerve and then pressed a heated iron against the dorsal thigh muscle to produce a burn. The defects were immediately repaired with an autograft (n = 10), nerve conduit graft (n = 8), or vascularized nerve conduit graft (n = 8). Recovery of motor function was examined for 18 weeks after surgery. The regenerated nerves were electrophysiologically and histologically evaluated. RESULTS: The vascularity of the nerve conduit implanted beneath the SIE vessels was confirmed histologically 2 weeks after implantation. Between 14 and 18 weeks after surgery, motor function of the vascularized conduit group was significantly better than that of the nonvascularized conduit group. Electrophysiological and histological evaluations revealed that although the improvement did not reach the level of reinnervation achieved by an autograft, the vascularized nerve conduit improved axonal regeneration more than did the conduit alone. CONCLUSION: Vascularization of artificial nerve conduits accelerated peripheral nerve regeneration, but further research is required to improve the quality of nerve regeneration. PMID- 27257596 TI - A Simple Method to Monitor Skin Cancer. PMID- 27257597 TI - HIV-Associated Cryptococcal Meningitis: Bridging the Gap Between Developed and Resource-Limited Settings. AB - Cryptococcal meningitis is a major cause of HIV-associated morbidity and mortality worldwide. Most cases occur in low-income countries, where over half of patients die within 10 weeks of diagnosis compared to as few as 10 % of patients from developed countries. A host of factors, spanning the HIV care continuum, are responsible for this gap in treatment outcomes between developed and resource limited settings. We explore factors responsible for this outcomes gap and describe low-cost, highly effective measures that can be implemented immediately to improve outcomes in resource-limited settings. We also explore health-system challenges that must be addressed to reduce mortality further, recent research in disease prevention, and novel short-course treatment regimens that, if efficacious, could be implemented in resource-limited settings where the cost of standard treatment regimens is currently prohibitive. PMID- 27257598 TI - PI3K p110beta subunit in leptin receptor expressing cells is required for the acute hypophagia induced by endotoxemia. AB - OBJECTIVE: Hypophagia and increased energy expenditure under inflammatory conditions, such as that observed after bacterial lipopolysaccharide (LPS) administration, are associated with leptin secretion. The hypophagic effect of leptin depends in part on the activation of PI3K signaling pathway. However, the role of PI3K in the endotoxemia-induced hypophagia has not been determined. METHODS: In an attempt to examine the functional contribution of the PI3K pathway in hypophagia and weight loss induced by LPS (100 ug/Kg, ip), we performed a central pharmacological PI3K inhibition (LY294002). Additionally, to gain mechanistic insights on the role of the catalytic PI3K p110alpha subunit in leptin responsive cells, mice expressing Cre-recombinase driven by the Lepr promoter (LepR-Cre) were crossed with mice carrying a loxP-modified p110alpha allele (Pi3kca gene) (LepR(Deltap110alpha)). As studies have suggested that the PI3K p110beta subunit has a dominant role over p110alpha in energy homeostasis, we further crossed LepR-Cre mice with loxP-modified p110alpha and p110beta (Pi3kcb gene) alleles (LepR(Deltap110alpha+beta)). In order to verify the requirement of leptin in PI3K effects on food intake, we also used leptin deficient ob/ob mice. RESULTS: We found that LPS stimulates PI3K and STAT3 signaling pathways in cells expressing the leptin receptor. Central PI3K inhibition prevented LPS-induced hypophagia and weight loss. Genetic deletion of p110alpha subunit selectively in LepR cells had no effect on LPS-induced hypophagia and weight loss. However, p110alpha and p110beta double deletion in LepR cells prevented LPS-induced hypophagia and partially reversed the weight loss. Leptin deficiency blunted LPS-induced acute pAKT and pSTAT3 phosphorylation and the acute suppression of food intake. CONCLUSIONS: Our studies show that the PI3K p110beta subunit in LepR cells is required for acute endotoxemic hypophagia. The data provide promising approaches for PI3K inhibition in preventing low energy balance and cachectic states during inflammatory challenges. PMID- 27257599 TI - Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia. AB - OBJECTIVE: To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. METHODS: We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naive mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. RESULTS: Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. CONCLUSIONS: Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet. PMID- 27257600 TI - A comprehensive lipidomic screen of pancreatic beta-cells using mass spectroscopy defines novel features of glucose-stimulated turnover of neutral lipids, sphingolipids and plasmalogens. AB - OBJECTIVE: Glucose promotes lipid remodelling in pancreatic beta-cells, and this is thought to contribute to the regulation of insulin secretion, but the metabolic pathways and potential signalling intermediates have not been fully elaborated. METHODS: Using mass spectrometry (MS) we quantified changes in approximately 300 lipid metabolites in MIN6 beta-cells and isolated mouse islets following 1 h stimulation with glucose. Flux through sphingolipid pathways was also assessed in (3)H-sphinganine-labelled cells using TLC. RESULTS: Glucose specifically activates the conversion of triacylglycerol (TAG) to diacylglycerol (DAG). This leads indirectly to the formation of 18:1 monoacylglycerol (MAG), via degradation of saturated/monounsaturated DAG species, such as 16:0_18:1 DAG, which are the most abundant, immediate products of glucose-stimulated TAG hydrolysis. However, 16:0-containing, di-saturated DAG species are a better direct marker of TAG hydrolysis since, unlike the 18:1-containing DAGs, they are predominately formed via this route. Using multiple reaction monitoring, we confirmed that in islets under basal conditions, 18:1 MAG is the most abundant species. We further demonstrated a novel site of glucose to enhance the conversion of ceramide to sphingomyelin (SM) and galactosylceramide (GalCer). Flux and product:precursor analyses suggest regulation of the enzyme SM synthase, which would constitute a separate mechanism for localized generation of DAG in response to glucose. Phosphatidylcholine (PC) plasmalogen (P) species, specifically those containing 20:4, 22:5 and 22:6 side chains, were also diminished in the presence of glucose, whereas the more abundant phosphatidylethanolamine plasmalogens were unchanged. CONCLUSION: Our results highlight 18:1 MAG, GalCer, PC(P) and DAG/SM as potential contributors to metabolic stimulus-secretion coupling. PMID- 27257601 TI - Role of mitochondrial uncoupling protein-2 (UCP2) in higher brain functions, neuronal plasticity and network oscillation. AB - BACKGROUND/PURPOSE: Major psychiatric illnesses, affecting 36% of the world's population, are profound disorders of thought, mood and behavior associated with underlying impairments in synaptic plasticity and cellular resilience. Mitochondria support energy demanding processes like neural transmission and synaptogenesis and are thus points of broadening interest in the energetics underlying the neurobiology of mental illness. These experiments interrogated the importance of mitochondrial flexibility in behavior, synaptic and cortical activity in a mouse model. METHODS: We studied mice with ablated uncoupling protein-2 expression (UCP2 KO) and analyzed cellular, circuit and behavioral attributes of higher brain regions. RESULTS: We found that mitochondrial impairment induced by UCP2 ablation produces an anxiety prone, cognitively impaired behavioral phenotype. Further, NMDA receptor blockade in the UCP2 KO mouse model resulted in changes in synaptic plasticity, brain oscillatory and sensory gating activities. CONCLUSIONS: We conclude that disruptions in mitochondrial function may play a critical role in pathophysiology of mental illness. Specifically, we have shown that NMDA driven behavioral, synaptic, and brain oscillatory functions are impaired in UCP2 knockout mice. PMID- 27257603 TI - A unique patient with epilepsy with cinematographic visual hallucinations. AB - PURPOSE: The purpose of this case report is to document a patient with cinematographic hallucinations, with corresponding right temporal lobe seizures on electroencephalogram (EEG). RESULTS: The results showed that the patient's EEG was normal. The patient subsequently reported hallucinations, which had been occurring for the last several months. During monitoring, no interictal EEG abnormalities were identified, but a total of 11 partial seizures were captured originating from the right posterior temporal area. They either were subclinical or corresponded with his visual hallucinations. CONCLUSION: The present study demonstrates focal seizures of temporal lobe origin producing complex visual hallucinations without a corresponding lesion on MRI brain imaging. PMID- 27257602 TI - Raptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease. AB - OBJECTIVE: Normal adipose tissue growth and function is critical to maintaining metabolic homeostasis and its excess (e.g. obesity) or absence (e.g. lipodystrophy) is associated with severe metabolic disease. The goal of this study was to understand the mechanisms maintaining healthy adipose tissue growth and function. METHODS: Adipose tissue senses and responds to systemic changes in growth factor and nutrient availability; in cells mTORC1 regulates metabolism in response to growth factors and nutrients. Thus, mTORC1 is poised to be a critical intracellular regulator of adipocyte metabolism. Here, we investigate the role of mTORC1 in mature adipocytes by generating and characterizing mice in which the Adiponectin-Cre driver is used to delete floxed alleles of Raptor, which encodes an essential regulatory subunit of mTORC1. RESULTS: Raptor (Adipoq-cre) mice have normal white adipose tissue (WAT) mass for the first few weeks of life, but soon thereafter develop lipodystrophy associated with hepatomegaly, hepatic steatosis, and insulin intolerance. Raptor (Adipoq-cre) mice are also resistant to becoming obese when consuming a high fat diet (HFD). Resistance to obesity does not appear to be due to increased energy expenditure, but rather from failed adipose tissue expansion resulting in severe hepatomegaly associated with hyperphagia and defective dietary lipid absorption. Deleting Raptor in WAT also decreases C/EBPalpha expression and the expression of its downstream target adiponectin, providing one possible mechanism of mTORC1 function in WAT. CONCLUSIONS: mTORC1 activity in mature adipocytes is essential for maintaining normal adipose tissue growth and its selective loss in mature adipocytes leads to a progressive lipodystrophy disorder and systemic metabolic disease that shares many of the hallmarks of human congenital generalized lipodystrophy. PMID- 27257604 TI - De novo transcriptome assembly of Sorghum bicolor variety Taejin. AB - Sorghum (Sorghum bicolor), also known as great millet, is one of the most popular cultivated grass species in the world. Sorghum is frequently consumed as food for humans and animals as well as used for ethanol production. In this study, we conducted de novo transcriptome assembly for sorghum variety Taejin by next generation sequencing, obtaining 8.748 GB of raw data. The raw data in this study can be available in NCBI SRA database with accession number of SRX1715644. Using the Trinity program, we identified 222,161 transcripts from sorghum variety Taejin. We further predicted coding regions within the assembled transcripts by the TransDecoder program, resulting in a total of 148,531 proteins. We carried out BLASTP against the Swiss-Prot protein sequence database to annotate the functions of the identified proteins. To our knowledge, this is the first transcriptome data for a sorghum variety derived from Korea, and it can be usefully applied to the generation of genetic markers. PMID- 27257605 TI - De novo transcriptome assembly of two Vigna angularis varieties collected from Korea. AB - The adzuki bean (Vigna angularis), a member of the family Fabaceae, is widely grown in Asia, from East Asia to the Himalayas. The adzuki bean is known as an ingredient that adds sweetness to diverse desserts made in Eastern Asian countries. Libraries prepared from two V. angularis varieties referred to as Taejin Black and Taejin Red were paired-end sequenced using the Illumina HiSeq 2000 system. The raw data in this study can be available in NCBI SRA database with accession numbers of SRR3406660 and SRR3406553. After de novo transcriptome assembly using Trinity, we obtained 324,219 and 280,056 transcripts from Taejin Black and Taejin Red, respectively. We predicted a total of 238,321 proteins and 179,519 proteins for Taejin Black and Taejin Red, respectively, by the TransDecoder program. We carried out BLASTP on the predicted proteins against the Swiss-Prot protein sequence database to predict the putative functions of identified proteins. Taken together, we provide transcriptomes of two adzuki bean varieties by RNA-Seq, which might be usefully applied to generate molecular markers. PMID- 27257606 TI - De novo transcriptome assembly of Setatria italica variety Taejin. AB - Foxtail millet (Setaria italica) belonging to the family Poaceae is an important millet that is widely cultivated in East Asia. Of the cultivated millets, the foxtail millet has the longest history and is one of the main food crops in South India and China. Moreover, foxtail millet is a model plant system for biofuel generation utilizing the C4 photosynthetic pathway. In this study, we carried out de novo transcriptome assembly for the foxtail millet variety Taejin collected from Korea using next-generation sequencing. We obtained a total of 8.676 GB raw data by paired-end sequencing. The raw data in this study can be available in NCBI SRA database with accession number of SRR3406552. The Trinity program was used to de novo assemble 145,332 transcripts. Using the TransDecoder program, we predicted 82,925 putative proteins. BLASTP was performed against the Swiss-Prot protein sequence database to annotate the functions of identified proteins, resulting in 20,555 potentially novel proteins. Taken together, this study provides transcriptome data for the foxtail millet variety Taejin by RNA-Seq. PMID- 27257607 TI - Genome sequencing and annotation of a Campylobacter coli strain isolated from milk with multidrug resistance. AB - As the most prevalent bacterial cause of human gastroenteritis, food-borne Campylobacter infections pose a serious threat to public health. Whole Genome Sequencing (WGS) is a tool providing quick and inexpensive approaches for analysis of food-borne pathogen epidemics. Here we report the WGS and annotation of a Campylobacter coli strain, FNW20G12, which was isolated from milk in the United States in 1997 and carries multidrug resistance. The draft genome of FNW20G12 (DDBJ/ENA/GenBank accession number LWIH00000000) contains 1, 855,435 bp (GC content 31.4%) with 1902 annotated coding regions, 48 RNAs and resistance to aminoglycoside, beta-lactams, tetracycline, as well as fluoroquinolones. There are very few genome reports of C. coli from dairy products with multidrug resistance. Here the draft genome of FNW20G12, a C. coli strain isolated from raw milk, is presented to aid in the epidemiology study of C. coli antimicrobial resistance and role in foodborne outbreak. PMID- 27257608 TI - A simple and rapid method for combining fluorescent in situ RNA hybridization (FISH) and immunofluorescence in the C. elegans germline. AB - Imaging of RNAs and proteins in specific tissues has opened ample avenues to understand gene expression during development. Recently, a fluorescent in situ RNA hybridization (FISH) method has been developed to analyze the spatio-temporal expression patterns of endogenous mRNAs. However, combining FISH with immunofluorescence is challenging as the reaction conditions for the two procedures conflict in multiple ways. In this report, we developed a simple and rapid method to detect both RNAs and associated proteins with better preservation of the fine structure in the C. elegans germline. This method will provide new tools for in vivo imaging of RNAs and their associated proteins in the same germline, which also enables simultaneous visualization of RNA/protein complex at the cellular level in vivo. *Developing a simple and rapid FISH method with better preservation of the fine structure.*Combining FISH with immunofluorescence in C. elegans germline.*Labeling extruded gonads, instead of the whole worms, to prevent non-specific somatic autofluorescence. PMID- 27257609 TI - Effect of fibrin glue on corneal lamellar healing and how it correlates to biomechanical properties: biomechanical wavefront analysis and confocal study. AB - BACKGROUND: To evaluate, using a rabbit model, the influence of the wound healing process at the flap edge on corneal biomechanics after sutured, glued, and non augmented microkeratome flaps. METHODS: Unilateral 160 MUm thick laser in situ keratomileusis (LASIK) flaps using a mechanical microkeratome were performed on the corneas of the left eyes of 36 rabbits. Animals were then divided into 3 groups of 12 rabbits each: A: the flaps were glued with human fibrin tissue adhesive (Tisseel); B: the flaps were sutured; and C: the flaps were allowed to heal without the use of sutures or glue (non-augmented). The contralateral eyes served as controls. Reichert ocular response analyzer (ORA) was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg) and cornea-compensated IOP (IOPcc) at 6 weeks and 3 months postoperatively. In vivo confocal microscopy (IVCM) was also used to study the corneal wound healing process in all groups. RESULTS: Both mean CH and mean CRF were significantly higher in sutured and glued groups compared with the non augmented group at 6 weeks and 3 months postoperatively (P < 0.0001). No statistically significant difference in corneal biomechanics was found between controls and groups A and B at any time points. Activated keratocytes were detected at the wound edge and peripheral flap interface in sutured and glued groups. CONCLUSION: The healing process at the wound edge is critical for optimal corneal integrity. Fibrin glue may serve as a safe and effective substitute to sutures in enhancing the corneal flap edge healing response and in increasing its mechanical strength. PMID- 27257610 TI - Corrigendum to "Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho-/- mouse". AB - [This corrects the article DOI: 10.1038/mtm.2015.16.]. PMID- 27257612 TI - Construction of Deletion-knockout Mutant Fowlpox Virus (FWPV). AB - The construction of deletion-knockout poxviruses is a useful approach to determining the function of specific virus genes. This protocol is an adaptation of the transient dominant knockout selection protocol published by Falkner and Moss (1990) for use with vaccinia virus. The protocol makes use of the dominant selectable marker Escherichia coli guanine phosphoribosyltransferase (gpt) gene (Mulligan and Berg, 1981), under the control of an early/late poxvirus promoter. The deletion viruses that are produced no longer contain a selectable marker, which may be preferable for the production of vaccines. PMID- 27257611 TI - Clinical development of gene therapy: results and lessons from recent successes. AB - Therapeutic gene transfer holds the promise of providing lasting therapies and even cures for diseases that were previously untreatable or for which only temporary or suboptimal treatments were available. For some time, clinical gene therapy was characterized by some impressive but rare examples of successes and also several setbacks. However, effective and long-lasting treatments are now being reported from gene therapy trials at an increasing pace. Positive outcomes have been documented for a wide range of genetic diseases (including hematological, immunological, ocular, and neurodegenerative and metabolic disorders) and several types of cancer. Examples include restoration of vision in blind patients, eradication of blood cancers for which all other treatments had failed, correction of hemoglobinopathies and coagulation factor deficiencies, and restoration of the immune system in children born with primary immune deficiency. To date, about 2,000 clinical trials for various diseases have occurred or are in progress, and many more are in the pipeline. Multiple clinical studies reported successful treatments of pediatric patients. Design of gene therapy vectors and their clinical development are advancing rapidly. This article reviews some of the major successes in clinical gene therapy of recent years. PMID- 27257613 TI - Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer's disease. AB - Alzheimer's disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer's disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article "Identification of proteins that are differentially expressed in brains with Alzheimer's disease using iTRAQ labeling and tandem mass spectrometry" (Minjarez et al., 2016) [1]. PMID- 27257614 TI - Dataset of Fourier transform-infrared coupled with chemometric analysis used to distinguish accessions of Garcinia mangostana L. in Peninsular Malaysia. AB - In this dataset, we distinguish 15 accessions of Garcinia mangostana from Peninsular Malaysia using Fourier transform-infrared spectroscopy coupled with chemometric analysis. We found that the position and intensity of characteristic peaks at 3600-3100 cm(-) (1) in IR spectra allowed discrimination of G. mangostana from different locations. Further principal component analysis (PCA) of all the accessions suggests the two main clusters were formed: samples from Johor, Melaka, and Negeri Sembilan (South) were clustered together in one group while samples from Perak, Kedah, Penang, Selangor, Kelantan, and Terengganu (North and East Coast) were in another clustered group. PMID- 27257615 TI - Bran data of total flavonoid and total phenolic contents, oxygen radical absorbance capacity, and profiles of proanthocyanidins and whole grain physical traits of 32 red and purple rice varieties. AB - Phytochemicals in red and purple bran rice have potential health benefit to humans. We determined the phytochemicals in brans of 32 red and purple global rice varieties. The description of the origin and physical traits of the whole grain (color, length, width, thickness and 100-kernel weight) of this germplasm collection are provided along with data of total flavonoid and total phenolic contents, oxygen radical absorbance capacity and total proanthocyanidin contents. The contents and proportions of individual oligomers, from degree of polymerization of monomers to 14-mers, and polymers in bran of these 32 rice varieties are presented (DOI: http://dx.doi.org/10.1016/j.foodchem.2016.04.004) [1]. PMID- 27257616 TI - Data on the distribution of physical activities in the Shenzhen greenway network with volunteered geographic information. AB - This data presents the distribution of physical activities in the Shenzhen greenway network (GN) in January, April and July, 2014. The volunteered geographic on physical activity is overlaid with the greenways data, to describe the distribution of physical activities in the greenways. The data are summarized to show the distribution characteristics geographically from different aspects in Shenzhen, China. Data were used to explore the effect of the Shenzhen GN on supporting physical activities, "Where do networks really work? The effects of Shenzhen greenway network on supporting physical activities" (Liu et al., 2016) [2]. PMID- 27257617 TI - Bid Promotes K63-Linked Polyubiquitination of Tumor Necrosis Factor Receptor Associated Factor 6 (TRAF6) and Sensitizes to Mutant SOD1-Induced Proinflammatory Signaling in Microglia. AB - Mutations in the superoxide dismutase 1 (SOD1) gene contribute to motoneuron degeneration and are evident in 20% of familial amyotrophic lateral sclerosis cases. Mutant SOD1 induces microglial activation through a stimulation of Toll like receptors 2 and 4 (TLR2 and TLR4). In the present study, we identified the proapoptotic Bcl-2 family protein Bid as a positive regulator of mutant SOD1 induced TLR-nuclear factor-kappaB (NF-kappaB) signaling in microglia. bid deficient primary mouse microglia showed reduced NF-kappaB signaling in response to TLR4 activation or exposure to conditioned medium derived from SOD1 (G93A) expressing NSC-34 cells. Attenuation of NF-kappaB signaling in bid-deficient microglia was associated with lower levels of phosphorylated IKKalpha/beta and p65, with a delayed degradation of IkappaBalpha and enhanced degradation of Peli1. Upstream of IKK, we found that Bid interacted with, and promoted, the K63 linked polyubiquitination of the E3 ubiquitin ligase tumor necrosis factor receptor associated factor 6 (TRAF6) in microglia. Our study suggests a key role for Bid in the regulation of TLR4-NF-kappaB proinflammatory signaling during mutant SOD1-induced disease pathology. Bid promotes TLR4-NF-kappaB signaling by interacting with TRAF6 and promoting TRAF6 K63-linked polyubiquitination in microglia. PMID- 27257618 TI - EPSPs Measured in Proximal Dendritic Spines of Cortical Pyramidal Neurons. AB - EPSPs occur when the neurotransmitter glutamate binds to postsynaptic receptors located on small pleomorphic membrane protrusions called dendritic spines. To transmit the synaptic signal, these potentials must travel through the spine neck and the dendritic tree to reach the soma. Due to their small size, the electrical behavior of spines and their ability to compartmentalize electrical signals has been very difficult to assess experimentally. In this study, we developed a method to perform simultaneous two-photon voltage-sensitive dye recording with two-photon glutamate uncaging in order to measure the characteristics (amplitude and duration) of uncaging-evoked EPSPs in single spines on the basal dendrites of L5 pyramidal neurons in acute brain slices from CD1 control mice. We were able to record uncaging-evoked spine potentials that resembled miniature EPSPs at the soma from a wide range of spine morphologies. In proximal spines, these potentials averaged 13.0 mV (range, 6.5-30.8 mV; N = 20) for an average somatic EPSP of 0.59 mV, whereas the mean attenuation ratio (spine/soma) was found to be 25.3. Durations of spine EPSP waveforms were found to be 11.7 ms on average. Modeling studies demonstrate the important role that spine neck resistance (Rneck) plays in spine EPSP amplitudes. Simulations used to estimate Rneck by fits to voltage-sensitive dye measurements produced a mean of 179 MOmega (range, 23-420 MOmega; N = 19). Independent measurements based on fluorescence recovery after photobleaching of a cytosolic dye from spines of the same population of neurons produced a mean R eck estimate of 204 MOmega (range, 52-521 MOmega; N = 34). PMID- 27257619 TI - Voltage Dependence of a Neuromodulator-Activated Ionic Current. AB - The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca(2+), but that, in conditions of low Ca(2+), calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca(2+)/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gbetagamma-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR. PMID- 27257621 TI - Fast Gamma Rhythms in the Hippocampus Promote Encoding of Novel Object-Place Pairings. AB - Hippocampal gamma rhythms increase during mnemonic operations (Johnson and Redish, 2007; Montgomery and Buzsaki, 2007; Sederberg et al., 2007; Jutras et al., 2009; Trimper et al., 2014) and may affect memory encoding by coordinating activity of neurons that code related information (Jensen and Lisman, 2005). Here, a hippocampal-dependent, object-place association task (Clark et al., 2000; Broadbent et al., 2004; Eacott and Norman, 2004; Lee et al., 2005; Winters et al., 2008; Barker and Warburton, 2011) was used in rats to investigate how slow and fast gamma rhythms in the hippocampus relate to encoding of memories for novel object-place associations. In novel object tasks, the degree of hippocampal dependence has been reported to vary depending on the type of novelty (Eichenbaum et al., 2007; Winters et al., 2008). Therefore, gamma activity was examined during three novelty conditions: a novel object presented in a location where a familiar object had been (NO), a familiar object presented in a location where no object had been (NL), and a novel object presented in a location where no object had been (NO+NL). The strongest and most consistent effects were observed for fast gamma rhythms during the NO+NL condition. Fast gamma power, CA3-CA1 phase synchrony, and phase-locking of place cell spikes increased during exploration of novel, compared to familiar, object-place associations. Additionally, place cell spiking during exploration of novel object-place pairings was increased when fast gamma rhythms were present. These results suggest that fast gamma rhythms promote encoding of memories for novel object-place associations. PMID- 27257620 TI - GluA2-Containing AMPA Receptors Distinguish Ribbon-Associated from Ribbonless Afferent Contacts on Rat Cochlear Hair Cells. AB - Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many "ribbonless" afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology. Only half the postsynaptic densities of type II afferents that labeled for PSD-95, Shank, or Homer were associated with GluA2 immunopuncta or presynaptic ribbons, the "empty slots" corresponding to ribbonless contacts described previously. These results extend the universality of AMPAergic transmission by hair cells, and support the existence of silent afferent contacts. PMID- 27257622 TI - No Effect of Subthalamic Deep Brain Stimulation on Intertemporal Decision-Making in Parkinson Patients. AB - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used treatment for the motor symptoms of Parkinson's disease (PD). DBS or pharmacological treatment is believed to modulate the tendency to, or reverse, impulse control disorders. Several brain areas involved in impulsivity and reward valuation, such as the prefrontal cortex and striatum, are linked to the STN, and activity in these areas might be affected by STN-DBS. To investigate the effect of STN-DBS on one type of impulsive decision-making--delay discounting (i.e., the devaluation of reward with increasing delay until its receipt)--we tested 40 human PD patients receiving STN-DBS treatment and medication for at least 3 months. Patients were pseudo-randomly assigned to one of four groups to test the effects of DBS on/off states as well as medication on/off states on delay discounting. The delay-discounting task consisted of a series of choices among a smaller. sooner or a larger, later monetary reward. Despite considerable effects of DBS on motor performance, patients receiving STN-DBS did not choose more or less impulsively compared with those in the off-DBS group, as well as when controlling for risk attitude. Although null results have to be interpreted with caution, our findings are of significance to other researchers studying the effects of PD treatment on impulsive decision-making, and they are of clinical relevance for determining the therapeutic benefits of using STN-DBS. PMID- 27257623 TI - Multiscale Aspects of Generation of High-Gamma Activity during Seizures in Human Neocortex. AB - High-gamma (HG; 80-150 Hz) activity in macroscopic clinical records is considered a marker for critical brain regions involved in seizure initiation; it is correlated with pathological multiunit firing during neocortical seizures in the seizure core, an area identified by correlated multiunit spiking and low frequency seizure activity. However, the effects of the spatiotemporal dynamics of seizure on HG power generation are not well understood. Here, we studied HG generation and propagation, using a three-step, multiscale signal analysis and modeling approach. First, we analyzed concurrent neuronal and microscopic network HG activity in neocortical slices from seven intractable epilepsy patients. We found HG activity in these networks, especially when neurons displayed paroxysmal depolarization shifts and network activity was highly synchronized. Second, we examined HG activity acquired with microelectrode arrays recorded during human seizures (n = 8). We confirmed the presence of synchronized HG power across microelectrode records and the macroscale, both specifically associated with the core region of the seizure. Third, we used volume conduction-based modeling to relate HG activity and network synchrony at different network scales. We showed that local HG oscillations require high levels of synchrony to cross scales, and that this requirement is met at the microscopic scale, but not within macroscopic networks. Instead, we present evidence that HG power at the macroscale may result from harmonics of ongoing seizure activity. Ictal HG power marks the seizure core, but the generating mechanism can differ across spatial scales. PMID- 27257624 TI - c-Jun N-Terminal Phosphorylation: Biomarker for Cellular Stress Rather than Cell Death in the Injured Cochlea. AB - Prevention of auditory hair cell death offers therapeutic potential to rescue hearing. Pharmacological blockade of JNK/c-Jun signaling attenuates injury induced hair cell loss, but with unsolved mechanisms. We have characterized the c Jun stress response in the mouse cochlea challenged with acoustic overstimulation and ototoxins, by studying the dynamics of c-Jun N-terminal phosphorylation. It occurred acutely in glial-like supporting cells, inner hair cells, and the cells of the cochlear ion trafficking route, and was rapidly downregulated after exposures. Notably, death-prone outer hair cells lacked c-Jun phosphorylation. As phosphorylation was triggered also by nontraumatic noise levels and none of the cells showing this activation were lost, c-Jun phosphorylation is a biomarker for cochlear stress rather than an indicator of a death-prone fate of hair cells. Preconditioning with a mild noise exposure before a stronger traumatizing noise exposure attenuated the cochlear c-Jun stress response, suggesting that the known protective effect of sound preconditioning on hearing is linked to suppression of c-Jun activation. Finally, mice with mutations in the c-Jun N-terminal phosphoacceptor sites showed partial, but significant, hair cell protection. These data identify the c-Jun stress response as a paracrine mechanism that mediates outer hair cell death. PMID- 27257625 TI - Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption. AB - The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 ug/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol. PMID- 27257627 TI - Only a Minority of the Inhibitory Inputs to Cerebellar Golgi Cells Originates from Local GABAergic Cells. AB - Cerebellar Golgi cells (GoCs) efficiently control the spiking activity of granule cells through GABAA receptor-mediated tonic and phasic inhibition. Recent experiments provided compelling evidence for the extensive interconnection of GoCs through electrical synapses, but their chemical inhibitory synaptic inputs are debated. Here, we investigated the GABAergic synaptic inputs of GoCs using in vitro electrophysiology and quantitative light microscopy (LM) and electron microscopy (EM). We characterized GABAA receptor-mediated IPSCs in GoCs and Lugaro cells (LuCs), and found that IPSCs in GoCs have lower frequencies, smaller amplitudes, and much slower decay kinetics. Pharmacological and LM immunolocalization experiments revealed that GoCs express alpha3, whereas LuCs express alpha1 subunit-containing GABAA receptors. The selective expression and clustered distribution of the alpha3 subunit in GoCs allowed the quantitative analysis of GABAergic synapses on their dendrites in the molecular layer (ML). EM and LM experiments in rats, and wild-type and GlyT2-GFP transgenic mice revealed that only one third of axon terminals establishing GABAergic synapses on GoC dendrites contain GlyT2, ruling out LuCs, globular cells, and any noncortical glycinergic inputs as major inhibitory sources. We also show that axon terminals of stellate/basket cells very rarely innervate GlyT2-GFP-expressing GoCs, indicating that only a minority of the inhibitory inputs to GoCs in the ML originates from local interneurons, and the majority of their inhibitory inputs exclusively releases GABA. PMID- 27257626 TI - TFEB Overexpression in the P301S Model of Tauopathy Mitigates Increased PHF1 Levels and Lipofuscin Puncta and Rescues Memory Deficits. AB - Transcription factor EB (TFEB) was recently shown to be a master regulator of autophagy lysosome pathway. Here, we successfully generated and characterized transgenic mice overexpressing flag-TFEB. Enhanced autophagy in the flag-TFEB transgenic mice was confirmed by an increase in the cellular autophagy markers, as determined by both immunoblots and transmission electron microscopy. Surprisingly, in the flag-TFEB mice we observed increased activity of senescence associated beta-galactosidase by ~66% of neurons in the cortex (p < 0.001) and 73% of neurons in the hippocampus (p < 0.001). More importantly, flag-TFEB expression remarkably reduced the levels of paired-helical filament (PHF)-tau from 372% in the P301S model of tauopathy to 171% (p < 0.001) in the cortex, and from 436% to 212% (p < 0.001) in the hippocampus. Significantly, reduced levels of NeuN in the cortex (38%, p < 0.001) and hippocampus (25%, p < 0.05) of P301S mice were almost completely restored to WT levels in the P301S/flag-TFEB double transgenic mice. Also, levels of spinophilin in both the cortex (p < 0.001) and hippocampus (p < 0.001) were restored almost to WT levels. Most importantly, the age-associated lipofuscin granules, which are generally presumed to be nondegradable, were reduced by 57% (p < 0.001) in the cortex and by 55% (p < 0.001) in the hippocampus in the double-transgenic mice. Finally, TFEB overexpression in the P301S mice markedly reversed learning deficits in terms of spatial memory (Barnes maze), as well as working and reference memories (T maze). These data suggest that the overexpression of TFEB can reliably enhance autophagy in vivo, reduce levels of PHF-tau, and thereby reverse the deposition of lipofuscin granules and memory deficits. PMID- 27257628 TI - Activity-Regulated Cytoskeleton-Associated Protein Controls AMPAR Endocytosis through a Direct Interaction with Clathrin-Adaptor Protein 2. AB - The activity-regulated cytoskeleton-associated (Arc) protein controls synaptic strength by facilitating AMPA receptor (AMPAR) endocytosis. Here we demonstrate that Arc targets AMPAR to be internalized through a direct interaction with the clathrin-adaptor protein 2 (AP-2). We show that Arc overexpression in dissociated hippocampal neurons obtained from C57BL/6 mouse reduces the density of AMPAR GluA1 subunits at the cell surface and reduces the amplitude and rectification of AMPAR-mediated miniature-EPSCs (mEPSCs). Mutations of Arc, that prevent the AP-2 interaction reduce Arc-mediated endocytosis of GluA1 and abolish the reduction in AMPAR-mediated mEPSC amplitude and rectification. Depletion of the AP-2 subunit u2 blocks the Arc-mediated reduction in mEPSC amplitude, an effect that is restored by reintroducing u2. The Arc-AP-2 interaction plays an important role in homeostatic synaptic scaling as the Arc-dependent decrease in mEPSC amplitude, induced by a chronic increase in neuronal activity, is inhibited by AP-2 depletion. These data provide a mechanism to explain how activity-dependent expression of Arc decisively controls the fate of AMPAR at the cell surface and modulates synaptic strength, via the direct interaction with the endocytic clathrin adaptor AP-2. PMID- 27257631 TI - Professional Oral Care Needs Further Evidence on Health Behaviour Change Outcomes. PMID- 27257632 TI - Errata. PMID- 27257629 TI - Abnormal UP/DOWN Membrane Potential Dynamics Coupled with the Neocortical Slow Oscillation in Dentate Granule Cells during the Latent Phase of Temporal Lobe Epilepsy. AB - The dentate gyrus, a major entry point to the hippocampus, gates (or filters) incoming information from the cortex. During sleep or anesthesia, the slow-wave oscillation (SWO) orchestrates hippocampus-neocortex communication, which is important for memory formation. The dentate gate is altered in temporal lobe epilepsy (TLE) early during epileptogenesis, which favors the propagation of pathological activities. Yet, whether the gating of physiological SWO by dentate granule cells (DGCs) is altered in TLE has remained unexplored. We combined intracellular recordings of membrane potential (V m) of DGCs and local field potential recordings of the SWO in parietal cortex in anesthetized rats early during epileptogenesis [post-status epilepticus (SE) rats]. As expected, in control rats, the V m of DGCs weakly and rarely oscillated in the SWO frequency range. In contrast, in post-SE rats, the V m of DGCs displayed strong and long lasting SWO. In these cells, clear UP and DOWN states, in phase with the neocortical SWO, led to a bimodal V m distribution. In post-SE rats, the firing of DGCs was increased and more temporally modulated by the neocortical SWO. We conclude that UP/DOWN state dynamics dominate the V m of DGCs and firing early during epileptogenesis. This abnormally strong neocortical influence on the dynamics of DGCs may profoundly modify the hippocampus-neocortex dialogue during sleep and associated cognitive functions. PMID- 27257633 TI - Correction: Mesoporous titania thin films as efficient enzyme carriers for paraoxon determination/detoxification: effects of enzyme binding and pore hierarchy on the biocatalyst activity and reusability. AB - Correction for 'Mesoporous titania thin films as efficient enzyme carriers for paraoxon determination/detoxification: effects of enzyme binding and pore hierarchy on the biocatalyst activity and reusability' by N. Francicet al., Analyst, 2014, 139, 3127-3136. PMID- 27257630 TI - A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis. AB - The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis. PMID- 27257634 TI - A supramolecular strategy based on molecular dipole moments for high-quality covalent organic frameworks. AB - A supramolecular strategy based on strong molecular dipole moments is presented to gain access to covalent organic framework structures with high crystallinity and porosity. Antiparallel alignment of the molecules within the pore walls is proposed to lead to reinforced columnar stacking, thus affording a high-quality material. As a proof of principle, a novel pyrene dione building block was prepared and reacted with hexahydroxytriphenylene to form a boronic ester-linked covalent organic framework. We anticipate the strategy presented herein to be valuable for producing highly defined COF structures. PMID- 27257635 TI - A highly selective and sensitive photoinduced electron transfer (PET) based HOCl fluorescent probe in water and its endogenous imaging in living cells. AB - A probe based on the phenothiazine-acridine orange conjugate (Ptz-AO) has been designed and synthesized for the sensitive and selective detection of HOCl. Ptz AO has excellent properties, including pH-independence of fluorescence, high resistance to photobleaching, and response in real time. The value of Ptz-AO was confirmed by exogenous, endogenous and the real-time imaging of HOCl in vitro using a fluorescence microscope. PMID- 27257636 TI - Silicone-based tough hydrogels with high resilience, fast self-recovery, and self healing properties. AB - Tough hydrogels are prepared from two monomers via photopolymerization of hydroxyethyl acrylate and sol-gel of methyltrimethoxysilane. Constitution and water content could be tuned easily because of the good water solubility of both monomers and two non-interfering polymerization processes. The hydrogels exhibit excellent integrated performance with toughness, high resilience, fast self recovery, and self-healing. PMID- 27257637 TI - Controlled formation of chiral networks and their reversible chiroptical switching behaviour by UV/microwave irradiation. AB - A 3D coordination polymer {[Cd(L(1))(L(2))]2}n (1) spontaneously resolves into enantiomorphic crystals of 1P and 1M without any chiral source. Bulk quantities of 1P and 1M can be predictably and reliably obtained by using chiral cyclohexane 1,2-diamine. 1 can be transformed into {[Cd(L(1))(L(3))0.5]2}n (2) by highly selective [2+2] photodimerization of L(2) ligands. The reverse process can be achieved by microwave irradiation. The cycloreversion/cycloaddition cycles result in chiroptical switching behavior. PMID- 27257638 TI - Stabilizing and color tuning pyrazine radicals by coordination for photochromism. AB - With the help of theoretical predictions, we have found, from the [donor-metal acceptor] system, the first photochromic pyrazine-based compound that can undergo photoinduced charge separation and yield stable pyrazine radicals. PMID- 27257639 TI - Magnetoresistance in Co/2D MoS2/Co and Ni/2D MoS2/Ni junctions. AB - Semiconducting single-layer (SL) and few-layer MoS2 have a flat surface, free of dangling bonds. Using density functional theory coupled with non-equilibrium Green's function method, we investigate the spin-polarized transport properties of Co/2D MoS2/Co and Ni/2D MoS2/Ni junctions with MoS2 layer numbers of N = 1, 3, and 5. Well-defined interfaces are formed between MoS2 and metal electrodes. The junctions with a SL MoS2 spacer are almost metallic owing to the strong coupling between MoS2 and the ferromagnets, while those are tunneling with a few layer MoS2 spacer. Both large magnetoresistance and tunneling magnetoresistance are found when fcc or hcp Co is used as an electrode. Therefore, flat single- and few layer MoS2 can serve as an effective nonmagnetic spacer in a magnetoresistance or tunneling magnetoresistance device with a well-defined interface. PMID- 27257640 TI - Charge-transport anisotropy in black phosphorus: critical dependence on the number of layers. AB - Phosphorene is a promising candidate for modern electronics because of the anisotropy associated with high electron-hole mobility. Additionally, superior mechanical flexibility allows the strain-engineering of various properties including the transport of charge carriers in phosphorene. In this work, we have shown the criticality of the number of layers to dictate the transport properties of black phosphorus. Trilayer black phosphorus (TBP) has been proposed as an excellent anisotropic material, based on the transport parameters using Boltzmann transport formalisms coupled with density functional theory. The mobilities of both the electron and the hole are found to be higher along the zigzag direction (~10(4) cm(2) V(-1) s(-1) at 300 K) compared to the armchair direction (~10(2) cm(2) V(-1) s(-1)), resulting in the intrinsic directional anisotropy. Application of strain leads to additional electron-hole anisotropy with 10(3) fold higher mobility for the electron compared to the hole. Critical strain for maximum anisotropic response has also been determined. Whether the transport anisotropy is due to the spatial or charge-carrier has been determined through analyses of the scattering process of electrons and holes, and their recombination as well as relaxation dynamics. In this context, we have derived two descriptors (S and F(k)), which are general enough for any 2D or quasi-2D systems. Information on the scattering involving purely the carrier states also helps to understand the layer-dependent photoluminescence and electron (hole) relaxation in black phosphorus. Finally, we justify trilayer black phosphorus (TBP) as the material of interest with excellent transport properties. PMID- 27257641 TI - Tuning Dirac points by strain in MoX2 nanoribbons (X = S, Se, Te) with a 1T' structure. AB - For practical applications of two-dimensional topological insulators, large band gaps and Dirac states within the band gap are desirable because they allow for device operation at room temperature and quantum transport without dissipation. Based on first-principles density functional calculations, we report the tunability of the electronic structure by strain engineering in quasi-one dimensional nanoribbons of transition metal dichalcogenides with a 1T' structure, MoX2 with X = (S, Se, Te). We find that both the band gaps and Dirac points in 1T'-MoX2 can be engineered by applying an external strain, thereby leading to a single Dirac cone within the bulk band gap. Considering the gap size and the location of the Dirac point, we suggest that, among 1T'-MoX2 nanoribbons, MoSe2 is the most suitable candidate for quantum spin Hall (QSH) devices. PMID- 27257643 TI - [Not Available]. PMID- 27257642 TI - [Time is a precious thing]. PMID- 27257644 TI - [Not Available]. PMID- 27257645 TI - [Not Available]. PMID- 27257646 TI - [Not Available]. PMID- 27257647 TI - [Not Available]. PMID- 27257649 TI - Morphology in mucopolysaccharidosis type III: specific diagnostic features. PMID- 27257648 TI - The proteome of the infectious bronchitis virus Beau-R virion. AB - Infectious bronchitis is a highly contagious respiratory disease of poultry caused by the coronavirus infectious bronchitis virus (IBV). It was thought that coronavirus virions were composed of three major viral structural proteins until investigations of other coronaviruses showed that the virions also include viral non-structural and genus-specific accessory proteins as well as host-cell proteins. To study the proteome of IBV virions, virus was grown in embryonated chicken eggs, purified by sucrose-gradient ultracentrifugation and analysed by mass spectrometry. Analysis of three preparations of purified IBV yielded the three expected structural proteins plus 35 additional virion-associated host proteins. The virion-associated host proteins had a diverse range of functional attributions, being involved in cytoskeleton formation, RNA binding and protein folding pathways. Some of these proteins were unique to this study, while others were found to be orthologous to proteins identified in severe acute respiratory syndrome coronavirus virions and also virions from a number of other RNA and DNA viruses. PMID- 27257650 TI - Deceased Heart Beating Donor and Organ Transplantation in Saudi Arabia. PMID- 27257651 TI - Hereditary angioedema: A call for collective terminology. PMID- 27257652 TI - Team building: Morale boosters. PMID- 27257653 TI - Digital forensics: from the crime lab to the library. PMID- 27257654 TI - HONORING TECHNOLOGY DEVELOPERS. PMID- 27257655 TI - Authors' Response. PMID- 27257656 TI - From the fringes of public health to the forefront of the fight against tobacco: Dr Judith Mackay. PMID- 27257657 TI - The "golden lotuses": bound feet. PMID- 27257658 TI - Viewpoint: Is there a nephrologist shortage or just poor deployment? PMID- 27257659 TI - Predictors of CKD and rate of decline in eGFR in the elderly: A case-cohort study. AB - We wanted to examine the predictors of annual estimated glomerular filtration rate (eGFR) decline during a five-year follow-up in elderly individuals with pre existing chronic kidney disease (CKD) stage 3 or greater (defined as baseline eGFR of less than 60 ml/min per 1.73 m2 or a urinary albumin-to-creatinine ratio > 30 mg/g), and to examine the difference in risk factors when compared to a co hort without CKD. Our research team identified 599 patients who were 65 years of age or older with and without CKD stage 3 or greater at baseline. Data regarding various predictors such as age, sex, race, proteinuria, medication use, contrast exposure, acute kidney injury episodes, coronary artery disease, congestive heart failure, dyslipidemia, gout etc. were obtained. Semi-partial correlations were used to determine the fac-tors providing the largest unique contribution to the overall variability in eGFR. Semi-partial correlations identified age, proteinuria, and intravenous contrast ex-posure as the most significant predictors of eGFR decline in this population. Overall, patients in the pre existing CKD cohort were more likely to be older, Af-rican American and with co morbidities like diabetes, hypertension, etc. In this group, the unadjusted rate of decline in eGFR varied from 0.5% to 8.3% per year. This study identifies important risk factors for eGFR decline in the population aged > 65 years. It also concludes that each episode of acute kidney injury, wheth-er related to contrast or other nephrotoxins, increases the risk for CKD progression and eGFR decline in the elderly. PMID- 27257660 TI - ANMF CALLS FOR 24/7 RN COVER AND BETTER WAGES IN AGED CARE. PMID- 27257661 TI - AGEISM TRIGGERS ELDER ABUSE IN AGED CARE. PMID- 27257662 TI - CARING FOR COGNITIVE IMPAIRMENT. PMID- 27257663 TI - NEW DIRECTIONS FOR ENROLLED NURSES. PMID- 27257664 TI - DEFINING QUALITY IN AGED CARE. PMID- 27257665 TI - NURSES AND MIDWIVES FROZEN OUT. PMID- 27257666 TI - AN OUNCE OF PREVENTION TO SAVE OUR HEALTHCARE. PMID- 27257667 TI - PROFESSIONAL ETHICS, BULLYING AND WORKPLACE CLIQUES. PMID- 27257668 TI - DIABETES. PMID- 27257669 TI - AN ENS ROLE. PMID- 27257670 TI - Application of Two-Dimensional Nuclear Magnetic Resonance for Signal Enhancement by Spectral Integration Using a Large Data Set of Metabolic Mixtures. AB - Nuclear magnetic resonance (NMR) spectroscopy has tremendous advantages of minimal sample preparation and interconvertibility of data among different institutions; thus, large data sets are frequently acquired in metabolomics studies. Previously, we used a novel analytical strategy, named signal enhancement by spectral integration (SENSI), to overcome the low signal-to-noise ratio (S/N ratio) problem in (13)C NMR by integration of hundreds of spectra without additional measurements. In this letter, the development of a SENSI 2D method and application to >1000 2D JRES NMR spectra are described. Remarkably, the obtained SENSI 2D spectrum had an approximate 14-fold increase in the S/N ratio and 80-250 additional peaks without any additional measurements. These results suggest that SENSI 2D is a useful method for assigning weak signals and that the use of coefficient of variation values can support the assignment information and extraction of features from the population characteristics among large data sets. PMID- 27257671 TI - Keeping All the PIECES: Phylogenetically Informed Ex Situ Conservation of Endangered Species. AB - Ex situ conservation in germplasm and living collections is a major focus of global plant conservation strategies. Prioritizing species for ex situ collection is a necessary component of this effort for which sound strategies are needed. Phylogenetic considerations can play an important role in prioritization. Collections that are more phylogenetically diverse are likely to encompass more ecological and trait variation, and thus provide stronger conservation insurance and richer resources for future restoration efforts. However, phylogenetic criteria need to be weighed against other, potentially competing objectives. We used ex situ collection and threat rank data for North American angiosperms to investigate gaps in ex situ coverage and phylogenetic diversity of collections and to develop a flexible framework for prioritizing species across multiple objectives. We found that ex situ coverage of 18,766 North American angiosperm taxa was low with respect to the most vulnerable taxa: just 43% of vulnerable to critically imperiled taxa were in ex situ collections, far short of a year-2020 goal of 75%. In addition, species held in ex situ collections were phylogenetically clustered (P < 0.001), i.e., collections comprised less phylogenetic diversity than would be expected had species been drawn at random. These patterns support incorporating phylogenetic considerations into ex situ prioritization in a manner balanced with other criteria, such as vulnerability. To meet this need, we present the 'PIECES' index (Phylogenetically Informed Ex situ Conservation of Endangered Species). PIECES integrates phylogenetic considerations into a flexible framework for prioritizing species across competing objectives using multi-criteria decision analysis. Applying PIECES to prioritizing ex situ conservation of North American angiosperms, we show strong return on investment across multiple objectives, some of which are negatively correlated with each other. A spreadsheet-based decision support tool for North American angiosperms is provided; this tool can be customized to align with different conservation objectives. PMID- 27257672 TI - Correction: The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014. AB - [This corrects the article DOI: 10.1371/journal.pone.0152676.]. PMID- 27257673 TI - Recurrent Microdeletions at Xq27.3-Xq28 and Male Infertility: A Study in the Czech Population. AB - BACKGROUND: Genetic causes of male infertility are hypothesized to involve multiple types of mutations, from single gene defects to complex chromosome rearrangements. Recently, several recurrent X-chromosome microdeletions (located in subtelomeric region of the long arm) were reported to be associated with male infertility in Spanish and Italian males. The aim of our study was to test their prevalence and infertility association in population of men from the Czech Republic. METHODS: 107 males with pathological sperm evaluation resulting in nonobstructive infertility were compared to 131 males with normal fecundity. X chromosome microdeletions were assessed by +/- PCR with three primer pairs for each region Xcnv64 (Xq27.3), Xcnv67 (Xq28) and Xcnv69 (Xq28). The latter microdeletion was further characterized by amplification across the deleted region, dividing the deletion into three types; A, B and C. RESULTS: We detected presence of isolated Xcnv64 deletion in 3 patients and 14 controls, and Xcnv69 in 3 patients and 6 controls (1 and 1 patient vs.4 and 1 control for types A and B respectively). There was one control with combined Xcnv64 and Xcnv69 type B deletions, and one patient with combination of Xcnv64 and Xcnv69 type C deletions. The frequency of the deletions was thus not higher in patient compared to control group, Xcnv64 was marginally associated with controls (adjusted Fisher's exact test P = 0.043), Xcnv69 was not associated (P = 0.452). We excluded presence of more extensive rearrangements in two subjects with combined Xcnv64 and Xcnv69 deletions. There was no Xcnv67 deletion in our cohort. CONCLUSION: In conclusion, the two previously reported X-linked microdeletions (Xcnv64 and Xcnv69) do not seem to confer a significant risk to impaired spermatogenesis in the Czech population. The potential clinical role of the previously reported patient-specific Xcnv67 remains to be determined in a larger study population. PMID- 27257675 TI - Correction: High-Fidelity Modelling Methodology of Light-Limited Photosynthetic Production in Microalgae. AB - [This corrects the article DOI: 10.1371/journal.pone.0152387.]. PMID- 27257674 TI - Feasibility of Quantifying Arterial Cerebral Blood Volume Using Multiphase Alternate Ascending/Descending Directional Navigation (ALADDIN). AB - Arterial cerebral blood volume (aCBV) is associated with many physiologic and pathologic conditions. Recently, multiphase balanced steady state free precession (bSSFP) readout was introduced to measure labeled blood signals in the arterial compartment, based on the fact that signal difference between labeled and unlabeled blood decreases with the number of RF pulses that is affected by blood velocity. In this study, we evaluated the feasibility of a new 2D inter-slice bSSFP-based arterial spin labeling (ASL) technique termed, alternate ascending/descending directional navigation (ALADDIN), to quantify aCBV using multiphase acquisition in six healthy subjects. A new kinetic model considering bSSFP RF perturbations was proposed to describe the multiphase data and thus to quantify aCBV. Since the inter-slice time delay (TD) and gap affected the distribution of labeled blood spins in the arterial and tissue compartments, we performed the experiments with two TDs (0 and 500 ms) and two gaps (300% and 450% of slice thickness) to evaluate their roles in quantifying aCBV. Comparison studies using our technique and an existing method termed arterial volume using arterial spin tagging (AVAST) were also separately performed in five subjects. At 300% gap or 500-ms TD, significant tissue perfusion signals were demonstrated, while tissue perfusion signals were minimized and arterial signals were maximized at 450% gap and 0-ms TD. ALADDIN has an advantage of visualizing bi-directional flow effects (ascending/descending) in a single experiment. Labeling efficiency (alpha) of inter-slice blood flow effects could be measured in the superior sagittal sinus (SSS) (20.8+/-3.7%.) and was used for aCBV quantification. As a result of fitting to the proposed model, aCBV values in gray matter (1.4-2.3 mL/100 mL) were in good agreement with those from literature. Our technique showed high correlation with AVAST, especially when arterial signals were accentuated (i.e., when TD = 0 ms) (r = 0.53). The bi-directional perfusion imaging with multiphase ALADDIN approach can be an alternative to existing techniques for quantification of aCBV. PMID- 27257676 TI - Antibioprophylaxis in Prevention of Endophthalmitis in Intravitreal Injection: A Systematic Review and Meta-Analysis. AB - Despite endophthalmitis being the most feared complication, antibioprophylaxis remains controversial in intravitreal injections. Therefore, we conducted a systematic review and meta-analysis on the effects of antibioprophylaxis in intravitreal injections in the prevention of endophthalmitis. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies comparing groups with and without antibiotics in intravitreal injection, with the use of the following keywords: "antibiotic*", "endophthalmitis" and "intravitreal injection*". To be included, studies needed to specify number of participants and number of endophthalmitis within each group (with and without antibiotics). We conducted meta-analysis on the prevalence of clinical endophthalmitis including both culture-proven and culture negative samples. Nine studies were included. A total of 88 incidences of endophthalmitis were reported from 174,159 injections (0.051% i.e., one incidence of endophthalmitis for 1979 injections). Specifically, 59 incidences of endophthalmitis were reported from 113,530 injections in the group with antibiotics (0.052% or one incidence of endophthalmitis for 1924 injections) and 29 incidences of endophthalmitis from 60,633 injections in the group without antibiotics (0.048% or one endophthalmitis for 2091 injections). Our meta-analysis did not report a significant difference in the prevalence of clinical endophthalimitis between the two groups with and without topical antibiotics: the odds ratio of clinical endophthalimitis was 0.804 (CI95% 0.384-1.682, p = 0.56) for the antibiotic group compared with the group without antibiotics. In conclusion, we performed the first large meta analysis demonstrating that antibioprophylaxis is not required in intravitreal injections. Strict rules of asepsis remain the only evidence-based prophylaxis of endophthalmitis. The results support initiatives to reduce the global threat of resistance to antibiotics. PMID- 27257677 TI - The Body and the Beautiful: Health, Attractiveness and Body Composition in Men's and Women's Bodies. AB - The dominant evolutionary theory of physical attraction posits that attractiveness reflects physiological health, and attraction is a mechanism for identifying a healthy mate. Previous studies have found that perceptions of the healthiest body mass index (weight scaled for height; BMI) for women are close to healthy BMI guidelines, while the most attractive BMI is significantly lower, possibly pointing to an influence of sociocultural factors in determining attractive BMI. However, less is known about ideal body size for men. Further, research has not addressed the role of body fat and muscle, which have distinct relationships with health and are conflated in BMI, in determining perceived health and attractiveness. Here, we hypothesised that, if attractiveness reflects physiological health, the most attractive and healthy appearing body composition should be in line with physiologically healthy body composition. Thirty female and 33 male observers were instructed to manipulate 15 female and 15 male body images in terms of their fat and muscle to optimise perceived health and, separately, attractiveness. Observers were unaware that they were manipulating the muscle and fat content of bodies. The most attractive apparent fat mass for female bodies was significantly lower than the healthiest appearing fat mass (and was lower than the physiologically healthy range), with no significant difference for muscle mass. The optimal fat and muscle mass for men's bodies was in line with the healthy range. Male observers preferred a significantly lower overall male body mass than did female observers. While the body fat and muscle associated with healthy and attractive appearance is broadly in line with physiologically healthy values, deviations from this pattern suggest that future research should examine a possible role for internalization of body ideals in influencing perceptions of attractive body composition, particularly in women. PMID- 27257678 TI - Correction: Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress. AB - [This corrects the article DOI: 10.1371/journal.pone.0154140.]. PMID- 27257679 TI - The Role of Seagrass Traits in Mediating Zostera noltei Vulnerability to Mesograzers. AB - Understanding how intra-specific differences in plant traits mediate vulnerability to herbivores of relevant habitat-forming plants is vital to attain a better knowledge on the drivers of the structure and functioning of ecosystems. Such studies, however, are rare in seagrass-mesograzer systems despite the increasingly recognized relevance of mesograzers as seagrass consumers. We investigated the role and potential trade-offs of multiple leaf traits in mediating the vulnerability of the seagrass Zostera noltei to different mesograzer species, the amphipod Gammarus insensibilis and the isopod Idotea chelipes. We worked with plants from two different meadows for which contrasting chemical and structural traits were expected based on previous information. We found that plants with high vulnerability to mesograzers (i.e. those preferred and subjected to higher rates of leaf area loss) had not only higher nitrogen content and lower C:N, fibre, and phenolics, but also tender and thinner leaves. No trade-offs between chemical and structural traits of the seagrass were detected, as they were positively correlated. When leaf physical structure was removed using agar-reconstituted food, amphipod preference towards high susceptibility plants disappeared; thus indicating that structural rather than chemical traits mediated the feeding preference. Removal of plant structure reduced the size of isopod preference to less than half, indicating a stronger contribution of structural traits (> 50%) but combined with chemical/nutritional traits in mediating the preference. We then hypothesized that the high environmental nutrient levels recorded in the meadow exhibiting high susceptibility modulate the differences observed between meadows in seagrass traits. To test this hypothesis, we exposed low-vulnerability shoots to eutrophic nutrient levels in a 6-week enrichment experiment. Nutrient enrichment increased Z. noltei nitrogen content and lowered C:N, fibre, and phenolics, but had no effect on structural traits. Overall, our findings help to better understand the trait-mediated seagrass susceptibility to mesograzers and reinforce the increasingly recognized role of structural defences against herbivory. PMID- 27257681 TI - Pairing Behavior of the Monogamous King Quail, Coturnix chinensis. AB - Animals with socially monogamous mating systems are valuable for discovering proximate mechanisms of prosocial behavior and close social relationships. Especially powerful are comparisons between related species that differ in monogamous tendency. Birds are the most socially monogamous vertebrates. Thus far most research on mechanisms of pairing has used zebra finches, which do not have a relative with a different mating system, however. The goal of the experiments reported here was to develop a new comparative avian system by studying the pairing behavior of a reportedly strongly monogamous quail, the king quail (Coturnix chinensis), a species in the same clade as the less monogamous Japanese quail (Coturnix japonica), the subject of much prior research. In Experiment 1 male-female pairs of king quail housed together were initially avoidant or aggressive but most rapidly progressed to allopreening and huddling. A separation reunion paradigm reliably elicited both of these behaviors in males that had cohabited for one week. In Experiment 2 the allopreening and huddling behavior of males in cohabiting pairs was highly selective, and a majority of the males were aggressive toward a familiar female that was not the cohabitation partner. In Experiment 3 males were separated from their female cohabitation partners for 9 10 weeks and then given two-choice tests. All but one male spent more time near an unfamiliar female, which may have reflected aggression and shows recognition of and memory for the past pairing experience. Thus king quail show robust, selective and easy to measure pairing behavior that can be reliably elicited with simple separation-reunion testing procedures. Copulation is rarely seen during tests. The behavior of king quail is a striking contrast to that of Japanese quail, providing a new comparative system for discovering mechanisms of behavior related to close social relationships and monogamy. PMID- 27257680 TI - Measures of Global Health Status on Dialysis Signal Early Rehospitalization Risk after Kidney Transplantation. AB - BACKGROUND: Early rehospitalization (<30 days) after discharge from kidney transplantation (KT) is associated with poor outcomes. We explored summary metrics of pre-transplant health status that may improve the identification of KT recipients at risk for early rehospitalization and mortality after transplant. MATERIALS AND METHODS: We performed a retrospective cohort study of 8,870 adult (>= 18 years) patients on hemodialysis who received KT between 2000 and 2010 at United States transplant centers. We linked Medicare data to United Network for Organ Sharing data and data from a national dialysis provider to examine pre-KT (1) Elixhauser Comorbidity Index, (2) physical function (PF) measured by the Short Form 36 Health Survey, and (3) the number of hospitalizations during the 12 months before KT as potential predictors of early rehospitalization after KT. We also explored whether these metrics are confounders of the known association between early rehospitalization and post-transplant mortality. RESULTS: The median age was 52 years (interquartile range [IQR] 41, 60) and 63% were male. 29% were rehospitalized in <30 days, and 20% died during a median follow-up time of five years (IQR 3.6-6.5). In a multivariable logistic model, kidney recipients with more pre-KT Elixhauser comorbidities (adjusted odds ratio [aOR] 1.09 per comorbidity, 95% Confidence Interval [CI] 1.07-1.11), the poorest pre-KT PF (aOR 1.24, 95% CI 1.08-1.43), or >1 pre-KT hospitalizations (aOR 1.32, 95% CI 1.17 1.49) were more likely to be rehospitalized. All three health status metrics and early rehospitalization were independently associated with post-KT mortality in a multivariable Cox model (adjusted hazard ratio for rehospitalization: 1.41, 95% CI 1.28-1.56). CONCLUSIONS: Pre-transplant metrics of health status, measured by dialysis providers or administrative data, are independently associated with early rehospitalization and mortality risk after KT. Transplant providers may consider utilizing metrics of pre-KT global health status as early signals of vulnerability when transitioning care after KT. PMID- 27257683 TI - Weakened Cholinergic Blockade of Inflammation Associates with Diabetes-Related Depression. AB - Emerging evidence demonstrates association of depression with both immune malfunctioning and worsened course of diverse aging-related diseases, but there is no explanation for the pathway(s) controlling this dual association. Here, we report that in post-reproductive and evolutionarily -blind" years, depression may weaken pathogen-host defense, compatible with the antagonistic pleiotropy hypothesis. In 15,532 healthy volunteers, depression scores associated with both inflammatory parameters and with increased circulation cholinesterase activities, implicating debilitated cholinergic blockade of inflammation as an underlying mechanism; furthermore, depression, inflammation and cholinesterase activities all increased with aging. In the entire cohort, combined increases in inflammation and the diabetic biomarker hemoglobin A1c associated with elevated depression. Moreover, metabolic syndrome patients with higher risk of diabetes showed increased cholinesterase levels and pulse values, and diabetic patients presented simultaneous increases in depression, inflammation and circulation cholinesterase activities, suggesting that cholinergic impairment precedes depression. Our findings indicate that dysfunctioning cholinergic regulation weakens the otherwise protective link between depression and pathogen-host defense, with global implications for aging-related diseases. PMID- 27257682 TI - The Third Intron of the Interferon Regulatory Factor-8 Is an Initiator of Repressed Chromatin Restricting Its Expression in Non-Immune Cells. AB - Interferon Regulatory Factor-8 (IRF-8) serves as a key factor in the hierarchical differentiation towards monocyte/dendritic cell lineages. While much insight has been accumulated into the mechanisms essential for its hematopoietic specific expression, the mode of restricting IRF-8 expression in non-hematopoietic cells is still unknown. Here we show that the repression of IRF-8 expression in restrictive cells is mediated by its 3rd intron. Removal of this intron alleviates the repression of Bacterial Artificial Chromosome (BAC) IRF-8 reporter gene in these cells. Fine deletion analysis points to conserved regions within this intron mediating its restricted expression. Further, the intron alone selectively initiates gene silencing only in expression-restrictive cells. Characterization of this intron's properties points to its role as an initiator of sustainable gene silencing inducing chromatin condensation with suppressive histone modifications. This intronic element cannot silence episomal transgene expression underlining a strict chromatin-dependent silencing mechanism. We validated this chromatin-state specificity of IRF-8 intron upon in-vitro differentiation of induced pluripotent stem cells (iPSCs) into cardiomyocytes. Taken together, the IRF-8 3rd intron is sufficient and necessary to initiate gene silencing in non-hematopoietic cells, highlighting its role as a nucleation core for repressed chromatin during differentiation. PMID- 27257684 TI - Implementation Considerations, Not Topological Differences, Are the Main Determinants of Noise Suppression Properties in Feedback and Incoherent Feedforward Circuits. AB - Biological systems use a variety of mechanisms to deal with the uncertain nature of their external and internal environments. Two of the most common motifs employed for this purpose are the incoherent feedforward (IFF) and feedback (FB) topologies. Many theoretical and experimental studies suggest that these circuits play very different roles in providing robustness to uncertainty in the cellular environment. Here, we use a control theoretic approach to analyze two common FB and IFF architectures that make use of an intermediary species to achieve regulation. We show the equivalence of both circuits topologies in suppressing static cell-to-cell variations. While both circuits can suppress variations due to input noise, they are ineffective in suppressing inherent chemical reaction stochasticity. Indeed, these circuits realize comparable improvements limited to a modest 25% variance reduction in best case scenarios. Such limitations are attributed to the use of intermediary species in regulation, and as such, they persist even for circuit architectures that combine both IFF and FB features. Intriguingly, while the FB circuits are better suited in dealing with dynamic input variability, the most significant difference between the two topologies lies not in the structural features of the circuits, but in their practical implementation considerations. PMID- 27257685 TI - Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages. AB - BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. METHODS: In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. RESULTS: Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). CONCLUSION: The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients. PMID- 27257687 TI - Visible Light-Induced Trifluoromethylation and Perfluoroalkylation of Cysteine Residues in Batch and Continuous Flow. AB - We report a visible light-induced trifluoromethylation and perfluoroalkylation for cysteine conjugation using Ru(bpy)3(2+) as photocatalyst and inexpensive RFI as coupling partner. The protocol allows the introduction of a variety of perfluoro alkyl groups (C1-C10) and a CF2COOEt moiety. The reaction is high yielding (56-94% yield) and fast (2 h in batch, 12 examples). Process intensification in a photomicroreactor accelerated the reaction (5 min reaction time) and increased the yields (8 examples). Quantum yield investigations support a radical chain mechanism. PMID- 27257686 TI - MicroRNA-27 Prevents Atherosclerosis by Suppressing Lipoprotein Lipase-Induced Lipid Accumulation and Inflammatory Response in Apolipoprotein E Knockout Mice. AB - Atherosclerotic lesions are lipometabolic disorder characterized by chronic progressive inflammation in arterial walls. Previous studies have shown that macrophage-derived lipoprotein lipase (LPL) might be a key factor that promotes atherosclerosis by accelerating lipid accumulation and proinflammatory cytokine secretion. Increasing evidence indicates that microRNA-27 (miR-27) has beneficial effects on lipid metabolism and inflammatory response. However, it has not been fully understood whether miR-27 affects the expression of LPL and subsequent development of atherosclerosis in apolipoprotein E knockout (apoE KO) mice. To address these questions and its potential mechanisms, oxidized low-density lipoprotein (ox-LDL)-treated THP-1 macrophages were transfected with the miR-27 mimics/inhibitors and apoE KO mice fed high-fat diet were given a tail vein injection with miR-27 agomir/antagomir, followed by exploring the potential roles of miR-27. MiR-27 agomir significantly down-regulated LPL expression in aorta and peritoneal macrophages by western blot and real-time PCR analyses. We performed LPL activity assay in the culture media and found that miR-27 reduced LPL activity. ELISA showed that miR-27 reduced inflammatory response as analyzed in vitro and in vivo experiments. Our results showed that miR-27 had an inhibitory effect on the levels of lipid both in plasma and in peritoneal macrophages of apoE KO mice as examined by HPLC. Consistently, miR-27 suppressed the expression of scavenger receptors associated with lipid uptake in ox-LDL-treated THP-1 macrophages. In addition, transfection with LPL siRNA inhibited the miR-27 inhibitor-induced lipid accumulation and proinflammatory cytokines secretion in ox-LDL-treated THP-1 macrophages. Finally, systemic treatment revealed that miR 27 decreased aortic plaque size and lipid content in apoE KO mice. The present results provide evidence that a novel antiatherogenic role of miR-27 was closely related to reducing lipid accumulation and inflammatory response via downregulation of LPL gene expression, suggesting a potential strategy to the diagnosis and treatment of atherosclerosis. PMID- 27257688 TI - Distinct Patterns of Association of Variants at 11q23.3 Chromosomal Region with Coronary Artery Disease and Dyslipidemia in the Population of Andhra Pradesh, India. AB - In our attempt to comprehensively understand the nature of association of variants at 11q23.3 apolipoprotein gene cluster region, we genotyped a prioritized set of 96 informative SNPs using Fluidigm customized SNP genotyping platform in a sample of 508 coronary artery disease (CAD) cases and 516 controls. We found 12 SNPs as significantly associated with CAD at P <0.05, albeit only four (rs2849165, rs17440396, rs6589566 and rs633389) of these remained significant after Benjamin Hochberg correction. Of the four, while rs6589566 confers risk to CAD, the other three SNPs reduce risk for the disease. Interaction of variants that belong to regulatory genes BUD13 and ZPR1 with APOA5 APOA4 intergenic variants is also observed to significantly increase the risk towards CAD. Further, ROC analysis of the risk scores of the 12 significant SNPs suggests that our study has substantial power to confer these genetic variants as predictors of risk for CAD, as illustrated by AUC (0.763; 95% CI: 0.729-0.798, p = <0.0001). On the other hand, the protective SNPs of CAD are associated with elevated Low Density Lipoprotein Cholesterol and Total Cholesterol levels, hence with dyslipidemia, in our sample of controls, which may suggest distinct effects of the variants at 11q23.3 chromosomal region towards CAD and dyslipidemia. It may be necessary to replicate these findings in the independent and ethnically heterogeneous Indian samples in order to establish this as an Indian pattern. However, only functional analysis of the significant variants identified in our study can provide more precise understanding of the mechanisms involved in the contrasting nature of their effects in manifesting dyslipidemia and CAD. PMID- 27257689 TI - Depth Echolocation Learnt by Novice Sighted People. AB - Some blind people have developed a unique technique, called echolocation, to orient themselves in unknown environments. More specifically, by self-generating a clicking noise with the tongue, echolocators gain knowledge about the external environment by perceiving more detailed object features. It is not clear to date whether sighted individuals can also develop such an extremely useful technique. To investigate this, here we test the ability of novice sighted participants to perform a depth echolocation task. Moreover, in order to evaluate whether the type of room (anechoic or reverberant) and the type of clicking sound (with the tongue or with the hands) influences the learning of this technique, we divided the entire sample into four groups. Half of the participants produced the clicking sound with their tongue, the other half with their hands. Half of the participants performed the task in an anechoic chamber, the other half in a reverberant room. Subjects stood in front of five bars, each of a different size, and at five different distances from the subject. The dimension of the bars ensured a constant subtended angle for the five distances considered. The task was to identify the correct distance of the bar. We found that, even by the second session, the participants were able to judge the correct depth of the bar at a rate greater than chance. Improvements in both precision and accuracy were observed in all experimental sessions. More interestingly, we found significantly better performance in the reverberant room than in the anechoic chamber. The type of clicking did not modulate our results. This suggests that the echolocation technique can also be learned by sighted individuals and that room reverberation can influence this learning process. More generally, this study shows that total loss of sight is not a prerequisite for echolocation skills this suggests important potential implications on rehabilitation settings for persons with residual vision. PMID- 27257690 TI - Simultaneous Native Nephrectomy and Kidney Transplantation in Patients With Autosomal Dominant Polycystic Kidney Disease. AB - INTRODUCTION: To evaluate the feasibility of simultaneous unilateral nephrectomy with kidney transplantation and to determine the effect of this procedure on perioperative morbidity and mortality and graft and patient survival. METHODS: Between January 2000 and May 2015, 145 patients with autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplantation. Of those, 40 (27.5%) underwent concurrent ipsilateral native nephrectomy (group NT). Patients in group NT were compared with patients with ADPKD not undergoing concurrent nephrectomy (group NT-) and asymptomatic patients undergoing pretransplant nephrectomy (group PNT). RESULTS: The average follow-up was 66 months. The graft survival rate at 1 and 5 years was 95% and 87.5% versus 93% and 76.2% in the NT and NT- groups, respectively (P = .903 and P = .544, respectively); 1-year patient survival was 100% for NT and 97% for NT- patients (P = .288), whereas 5 year patient survival was 100% and 92% for NT and NT- groups, respectively (P = .128). After propensity score matching (34 patients per group) no significant differences were observed in 1-year (97.1% in NT and 94.1%; P = 1) and 5-year (88.2% in NT and 91.2% in NT-; P = 1) graft survival, and in 1-year (100% for both groups; P = 1) and 5-year (100% in NT and 94.1% in NT-; P = 1) patient survival. Perioperative mortality was 0% among NT and 1.2% among NT- patients, whereas perioperative surgical complications were similar in both groups. One- and 5-year graft and patient survival were similar between the NT and PNT groups, but patients in the PNT group had significantly lower levels of hemoglobin and residual diuresis volumes at the time of transplant. Moreover, PNT patients had a longer pretransplant dialysis and a longer time on the waiting list. CONCLUSIONS: Simultaneous unilateral nephrectomy does not have a negative effect on patient and graft survival in patients with ADPKD and is associated with low morbidity. Pretransplant nephrectomy should be restricted only to highly symptomatic patients, whereas unilateral nephrectomy in asymptomatic patients should be performed during kidney transplantation only if massive kidney size precludes graft positioning. PMID- 27257691 TI - Time and place of death from automobile crashes: Research endpoint implications. AB - BACKGROUND: Vehicle crashes are a leading cause of US injury and death. Early death, however, has almost entirely been studied in-hospital. The US Department of Transportation Fatality Analysis Reporting System (FARS) database captures both prehospital and in-hospital mortality. METHODS: FARS location (prehospital, in-hospital) and time of death were reviewed (1978-2013), and a 2003-2005 subgroup of 55,537 early deaths (i.e., between 5 minutes and 4 hours after injury) was analyzed to quantify risk of death over time. RESULTS: There has been an overall decrease in 1978-2013 US vehicle-related deaths (from 3.3 deaths per 100 million vehicle miles traveled to 1.1 and from 22.6 per 100,000 population to 10.4). Snapshots of the death data reveal an overall downward trend of total in hospital and prehospital deaths. The proportion of hospital deaths decreased by 58%, whereas the proportion of deaths in the prehospital period increased to 56%. Subgroup analysis revealed a rate of mortality risk of 0.4% per minute for the first 30 minutes, 1% per minute for the next 60 minutes, and 0.2% per minute and plateauing thereafter. CONCLUSIONS: Analysis of census FARS data of motor vehicle crash-related deaths showed an overall 35% decrease in mortality over a period of 36 years. The disproportionate reduction in in-hospital deaths is perhaps a testament to the effectiveness of trauma centers. However, there is a demonstrable need to focus on prehospital deaths with resuscitative and adjuvant therapy research and trauma system design. Quantifying risk of death over time should help focus emergency medical services, trauma system, and resuscitation goals. LEVEL OF EVIDENCE: Epidemiologic study, level III. PMID- 27257692 TI - Civilian casualties of terror-related explosions: The impact of vascular trauma on treatment and prognosis. AB - OBJECTIVES: A high prevalence (10%) of vascular trauma (VT) was previously described in terror-related trauma as compared with non-terror-related trauma (1%), in a civilian setting. No data regarding outcome of VT casualties of improvised explosive device (IED) explosions, in civilian settings, are available. The aim of the current study is to present the prognosis of civilian casualties of IED explosions with and without VT. METHODS: A retrospective analysis of the Israeli National Trauma Registry was performed. All patients in the registry from September 2000 to December 2005 who were victims of explosions were included. These patients were subdivided into patients with VT (n = 109) and non-VT (NVT) (n = 1,152). Both groups were analyzed according to mechanism of trauma, type and severity of injury, and treatment. RESULTS: Of 1,261 explosion casualties, there were 109 VT victims (8.6%). Patients with VT tended to be more complex, with a higher injury severity score (ISS): 17.4% with ISS 16 to 24 as compared with only 10.5%. In the group of critically injured patients (ISS, 25 75), 51.4% had VT compared with only 15.5% of the NVT patients. As such, a heavy share of hospitals' resources were used-trauma bay admission (62.4%), operating rooms (91.7%), and intensive care unit beds (55.1%). The percentage of VT patients who were admitted for more than 15 days was 2.3 times higher than that observed among the NVT patients. Lower-extremity VT injuries were the most prevalent. Although many resources are being invested in treating this group of patients, their mortality rate is approximately five times more than NVT (22.9% vs. 4.9%). CONCLUSIONS: Vascular trauma casualties of IED explosions are more complex and have poorer prognosis. Their higher ISS markedly increases the hospital's resource utilization, and as such, it should be taken into consideration either upon the primary evacuation from the scene or when secondary modulation is needed in order to reduce the burden of the hospitals receiving the casualties. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level V. PMID- 27257693 TI - Re: Ultrasonography for resuscitative endovascular balloon occlusion of the aorta: A practical leap forward using microbubble contrast agent. PMID- 27257694 TI - Emergency general surgery specific frailty index: A validation study. AB - INTRODUCTION: Assessment of operative risk in geriatric patients undergoing emergency general surgery (EGS) is challenging. Frailty is an established measure for risk assessment in surgical cases. The aim of our study was to validate a modified 15-variable EGS-specific frailty index (EGSFI). METHODS: We prospectively collected geriatric (age older than 65 years) EGS patients for 2 years. Postoperative complications were collected. Frailty index was calculated for 200 patients based on their preadmission condition using 50-variable modified Rockwood frailty index. Emergency general surgery-specific frailty index was developed based on the regression model for complications and the most significant factors in the frailty index. Receiver operating characteristic curve analysis was performed to determine cutoff for frail status. We validated our results using 60 patients for predicting complications. RESULTS: A total of 260 patients (developing, 200; validation, 60) were enrolled in this study. Mean age was 71 +/- 11 years, and 33% developed complications. Most common complications were pneumonia (12%), urinary tract infection (9%), and wound infection (7%). Univariate analysis identified 15 variables significantly associated with complications that were used to develop the EGSFI. A cutoff frailty score of 0.325 was identified using receiver operating characteristic curve analysis for frail status. Sixty patients (frail, 18; nonfrail, 42) were enrolled in the validation cohort. Frail patients were more likely to have postoperative complications (47% vs. 20%; p < 0.001) compared to nonfrail patients. Frail status based on EGSFI was a significant predictor of postoperative complications (odds ratio, 7.3; 95% confidence interval, 1.7-19.8; p = 0.006). Age was not associated with postoperative complications (odds ratio, 0.99; 95% confidence interval, 0.92-1.06; p = 0.86). CONCLUSION: The 15-variable validated EGSFI is a simple and reliable bedside tool to determine the frailty status of patients undergoing EGS. Frail status as determined by the EGSFI is an independent predictor of postoperative complications and mortality in geriatric EGS patients. LEVEL OF EVIDENCE: Prognostic study, level II. PMID- 27257695 TI - Ultrasonography for resuscitative endovascular balloon occlusion of the aorta: A practical leap forward using microbubble contrast agent. PMID- 27257696 TI - The American Association for the Surgery of Trauma grading scale for 16 emergency general surgery conditions: Disease-specific criteria characterizing anatomic severity grading. PMID- 27257697 TI - Field intubation for hemorrhagic shock: A flawed syllogism. PMID- 27257698 TI - Hepatic and splenic blush on computed tomography in children following blunt abdominal trauma: Is intervention necessary? AB - BACKGROUND: There are no widely accepted guidelines for management of pediatric patients who have evidence of solid organ contrast extravasation ("blush") on computed tomography (CT) scans following blunt abdominal trauma. We report our experience as a Level 1 pediatric trauma center in managing cases with hepatic and splenic blush. METHODS: All pediatric blunt abdominal trauma cases resulting in liver or splenic injury were queried from 2008 to 2014. Patients were excluded if a CT was unavailable in the medical record. The presence of contrast blush was based on final reports from attending pediatric radiologists. Correlations between incidence of contrast blush and major outcomes of interest were determined using chi and Wilcoxon rank-sum tests for categorical and continuous variables, respectively, evaluating statistical significance at p < 0.05. RESULTS: Of 318 patients with splenic or liver injury after blunt abdominal trauma, we report on 30 patients (9%) with solid organ blush, resulting in 18 cases of hepatic blush and 16 cases of splenic blush (four patients had extravasation from both organs). Blush was not found to correlate significantly with age, gender, or type of injury (liver vs. splenic) but was found to associate with higher grades of solid organ injury (p = 0.002) and higher ISS overall (p < 0.001). Patients with contrast blush on imaging were more likely to be admitted to the intensive care unit (90% vs. 41%, p < 0.001), receive blood products, (50% vs. 12%, p < 0.001), and be considered for an intervention (p < 0.001). Eighty percent of patients with an isolated contrast blush of the spleen or liver did not require an operation. Only 17% of patients with blush required definitive treatment, such as embolization (n = 1), packing (n = 1), or splenectomy (n = 3). Blush had no significant correlation with overall survival (p = 0.13). CONCLUSIONS: The finding of a blush on CT from a splenic or liver injury is associated with higher grade of injury. These patients receive intensive medical management but do not uniformly require invasive intervention. From our data, we suggest that a blush can safely be managed nonoperatively and that treatment should be dictated by change in physiology. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 27257700 TI - The term "prehospital" must be justified when reporting animal studies of traumatic hemorrhagic shock. PMID- 27257701 TI - Re: Field intubation for hemorrhagic shock: A flawed syllogism. PMID- 27257702 TI - Severe complicated Clostridium difficile infection: Can the UPMC proposed scoring system predict the need for surgery? AB - INTRODUCTION: Clostridium difficile infection (CDI) is one of the most common health care-associated infections, and it continues to have significant morbidity and mortality. The onset of fulminant colitis often requires total abdominal colectomy with ileostomy, which has a mortality rate of 35% to 57%. University of Pittsburgh Medical Center (UPMC) developed a scoring system for severity and recommended surgical consultation for severe complicated disease. The aim of this study was to evaluate if the UPMC-proposed scoring system for severe complicated CDI can predict the need for surgical intervention. METHODS: This is a retrospective review of all patients who developed severe complicated CDI at Geisinger Medical Center between January 2007 and December 2012 as defined by the UPMC scoring system. Main outcomes were the need for surgical intervention and 30 day mortality. RESULTS: Eighty-eight patients had severe complicated CDI based on the UPMC scoring system. Fifty-nine patients (67%) required surgery and 29 did not. All patients had a diagnosis of CDI as shown by positive toxin assays. There was no difference between the groups with respect to age, sex, body mass index, or comorbidities. When comparing the surgical group to the nonsurgical cohort, the surgical cohort averaged 20 points on the scoring system compared to 9 in the nonoperative cohort. In patients with severe complicated CDI, 15 or more points predicted the need for surgery 75% of the time. Forty-two percent of the surgical cohort had respiratory failure requiring mechanical ventilation compared to 0% in the nonsurgical cohort (p < 0.0001). Forty-nine percent of the surgical cohort required vasopressors for septic shock before surgery compared to 0% in the nonsurgical cohort (p < 0.0001). Acute kidney injury was present in 92% of the surgical cohort versus 72% within the nonsurgical cohort (p = 0.026). Seventy-six percent of the surgical patients were admitted to the ICU before surgery. Within the nonsurgical cohort, only 24% of patients required ICU stay during admission. Overall, 30-day mortality in the surgical cohort was 30%, and there was no mortality in the nonsurgical cohort. CONCLUSIONS: The UPMC scoring system for severe complicated CDI can help us predict patients who need a surgical consult and the need for surgical intervention. In patients with severe complicated CDI, evidence of end-organ failure predicts surgical intervention. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV. PMID- 27257703 TI - Comparison of the Prehospital Trauma Life Support recommendations and the German national guideline on treatment of patients with severe and multiple injuries. AB - BACKGROUND: The Prehospital Trauma Life Support (PHTLS) concept is well established throughout the world. The aim is to improve prehospital care for patients with major trauma. In 2011, a German Level 3 (S3) evidence- and consensus-based guideline on the treatment of patients with severe and multiple injuries was published. The scope of this study was the systematic comparison between the educational content of the worldwide PHTLS concept and the German S3 Guideline. METHODS: A total of 62 key recommendations of the German S3 Guideline were compared with the content of the English PHTLS manual (eighth edition). Depending on the level of agreement, the recommendations were categorized as (1) agreement, (2) minor variation, or (3) major variation. Comparison was done via a rating system by a number of international experts in the field of out-of hospital trauma care. The Delphi method was used to get the final statements by indistinct or board-ranged ratings. RESULTS: Overall, there was no conformity in 12%. In 68% a total agreement and in 88% conformity with slight differences of minor variations were found between the key recommendations of the guideline and the PHTLS manual. The PHTLS primary assessment has a large conformity for the following individual priorities: airway, 92%; breathing, 92%; circulation, 63%; disability, 100%; exposure, 89%. CONCLUSIONS: According to our comparison, the PHTLS manual is largely compatible with the German S3 Guideline from 2011. The 12% divergent statements concern mainly fluid resuscitation. Minor deviations in the prehospital care are due to a national guideline with an emergency medical service with emergency physicians (S3 Guideline) and a global PHTLS concept. PMID- 27257704 TI - A multi-institutional study of hemostatic gauze and tourniquets in rural civilian trauma. AB - BACKGROUND: Life-threatening hemorrhage is a leading cause of preventable mortality in trauma patients. Since publication of the Hartford Consensus statement, there has been intense interest in civilian use of commercial hemostatic gauze and tourniquets. Although the military has studied their use on soldiers with wartime injuries, there are limited data on patient outcomes following civilian prehospital use and no data on the use in rural trauma. METHODS: We performed a multi-institutional retrospective analysis of clinical outcomes following prehospital use of QuikClot combat gauze (QC) and combat application tourniquets (CATs) from 2009 to 2014. The primary outcome measured was effectiveness. Secondary outcomes included morbidity, mortality, patients' demographics, injury characteristics, and hospital outcomes. RESULTS: Between 2009 and 2014, 95 patients were managed by prehospital personnel with QC and/or CAT. Forty received QC, 61 received CAT, and 6 received both products. The median age was 40 years (6-91 years), 29% were female, and the median injury severity score was 7 (1-25). QuikClot combat gauze was 89% effective. Minimal morbidity was associated with QC use. Combat application tourniquet was 98% effective. Median tourniquet time was 21 minutes (6-142 minutes), the median injury severity score was 9 (1-50), and mortality was 9.8%. Morbidities observed with tourniquet use included amputation, fasciotomy, rhabdomyolysis, and acute kidney injury. Risk of amputation was associated with higher injury severity (p = 0.04) but not with elderly age, obesity, or the presence of medical comorbidities. No amputations resulted solely from the use of tourniquets. CONCLUSIONS: QuikClot combat gauze and CAT are safe and effective adjuncts for hemorrhage control in the rural civilian trauma across a wide range of injury patterns. In a rural civilian population including women, children, and elderly patients with medical comorbidities, these devices are associated with minimal morbidity beyond that of the original injury. LEVEL OF EVIDENCE: Therapeutic study, level V. PMID- 27257705 TI - What is the effectiveness of the negative pressure wound therapy (NPWT) in patients treated with open abdomen technique? A systematic review and meta analysis. AB - BACKGROUND: The open abdomen technique may be used in critically ill patients to manage abdominal injury, reduce the septic complications, and prevent the abdominal compartment syndrome. Many different techniques have been proposed and multiple studies have been conducted, but the best method of temporary abdominal closure has not been determined yet. Recently, new randomized and nonrandomized controlled trials have been published on this topic. We aimed to perform an up-to date systematic review on the management of open abdomen, including the most recent published randomized and nonrandomized controlled trials, to compare negative pressure wound therapy (NPWT) with no NPWT and define if one technique has better outcomes than the other with regard to primary fascial closure, postoperative 30-day mortality and morbidity, enteroatmospheric fistulae, abdominal abscess, bleeding, and length of stay. METHODS: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and the Cochrane Handbook for Systematic Reviews of Interventions, an online literature research (until July 1, 2015) was performed on MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, and Cochrane Library databases. The MeSH terms and free words used "vacuum assisted closure" "vac;", "open abdomen", "damage control surgery", and "temporary abdominal closure". No language restriction was made. RESULTS: The initial systematic literature search yielded 452 studies. After a careful assessment of the titles and of the full text was obtained, eight articles fulfilled inclusion criteria. We analyzed 1,225 patients, of whom 723 (59%) underwent NPWT and 502 (41%) did not undergo NPWT, and performed four subgroups: VAC versus Bogota bag technique (two studies, 106 participants), VAC versus mesh-foil laparostomy (two studies, 159 participants), VAC versus laparostomy (adhesive impermeable with midline zip) (one study, 106 participants), and NPWT versus no NPWT techniques (three studies, 854 participants) in which it is not possible to perform an analysis of the different types of treatment. Comparing the NPWT group and the group without NPWT, there was no statistically significant difference in fascial closure (63.5% vs 69.5%; odds ratio [OR], 0.74; 95% confidence interval [CI], 0.27-2.06; p = 0.57), postoperative 30-day overall morbidity (p = 0.19), postoperative enteroatmospheric fistulae rate (2.1% vs 5.8%; OR, 0.63; 95% CIs, 0.12-3.15; p = 0.57), in the postoperative bleeding rate (5.7% vs 14.9%; OR, 0.58; 95% CIs, 0.05 6.84; p = 0.87), and postoperative abdominal abscess rate (2.4% vs 5.6%; OR, 0.42; 95% CI, 0.13-1.34; p = 0.14). On the other hand, statistical significance was found between the NPWT group and the group without NPWT in the postoperative mortality rate (28.5% vs 41.4%; OR, 0.46; 95% CI, 0.23-0.91; p = 0.03) and in the length of stay in the intensive care unit (mean difference, -4.53; 95% CI, -5.46 to 3.60; p < 0.00001). CONCLUSION: The limitations of the present analysis might be related to the lack of randomized controlled trials, so there is a risk of selection bias favoring NPWT. For several outcomes, there were few studies, confidence intervals were wide, and inconsistency was high, suggesting that although there were no statistically significant differences between the groups, there was insufficient evidence to show that the outcomes were similar. We can conclude from the current available data that NPWT seems to be associated with a trend toward better outcomes compared to the use of no NPWT. It does reflect the evidence presented in the current systematic review; however, the data should be interpreted with substantial caution given a number of weaknesses (in particular, the lack of statistical significance and heterogeneity between studies, i.e., small sample size of the included studies, high variability between studies). We highlight the need for randomized controlled trials having homogeneous inclusion criteria to assess the use of NPWT for the management of open abdomen. LEVEL OF EVIDENCE: Systemic review/meta-analysis, level III. PMID- 27257706 TI - Is there an impending loss of academically productive trauma surgical faculty? An analysis of 4,015 faculty. AB - OBJECTIVE: The aim of this work was to compare the academic impact of trauma surgery faculty relative to faculty in general surgery and other surgery subspecialties. METHODS: Scholarly metrics were determined for 4,015 faculty at the top 50 National Institutes of Health (NIH)-funded university-based departments and five hospital-based surgery departments. RESULTS: Overall, 317 trauma surgical faculty (8.2%) were identified. This compared to 703 other general surgical faculty (18.2%) and 2,830 other subspecialty surgical faculty (73.5%). The average size of the trauma surgical division was six faculty. Overall, 43% were assistant professors, 29% were associate professors, and 28% were full professors, while 3.1% had PhD, 2.5% had MD and PhD, and, 16.3% were division chiefs/directors. Compared with general surgery, there were no differences regarding faculty academic levels or leadership positions. Other surgical specialties had more full professors (39% vs. 28%; p < 0.05) and faculty with research degrees (PhD, 7.7%; and MD and PhD, 5.7%). Median publications/citations were lower, especially for junior trauma surgical faculty (T) compared with general surgery (G) and other (O) surgical specialties: assistant professors (T, 9 publications/76 citations vs. G, 13/138, and O, 18/241; p < 0.05), associate professors (T, 22/351 vs. G, 36/700, and O, 47/846; p < 0.05), and professors (T, 88/2,234 vs. G, 93/2193; p = NS [not significant for either publications/citations] and O, 99/2425; p = NS). Publications/Citations for division chiefs/directors were comparable with other specialties: T, 77/1,595 vs. G, 103/2,081 and O, 74/1,738; p = NS, but were lower for all nonchief faculty; T, 23/368 vs. G, 30/528 and O, 37/658; p < 0.05. Trauma surgical faculty were less likely to have current or former NIH funding than other surgical specialties (17 % vs. 27%; p < 0.05), and this included a lower rate of R01/U01/P01 funding (5.5% vs. 10.8%; p < 0.05). CONCLUSIONS: Senior trauma surgical faculty are as academically productive as other general surgical faculty and other surgical specialists. Junior trauma faculty, however, publish at a lower rate than other general surgery or subspecialty faculty. Causes of decreased academic productivity and lower NIH funding must be identified, understood, and addressed. PMID- 27257707 TI - Augmented renal clearance in non-critically ill abdominal and trauma surgery patients is an underestimated phenomenon: A point prevalence study. AB - BACKGROUND: Augmented renal clearance refers to increased renal elimination of circulating solutes as compared with normal baseline and could lead to underexposure of frequently used renally eliminated antimicrobials. The primary objective was to assess the prevalence of augmented renal clearance in an adult non-critically ill surgery population. Besides, predictors for augmented renal clearance were investigated. A prospective observational single-center point prevalence study was conducted. METHODS: The measured creatinine clearance based on an 8-hour urinary collection was used as primary method for determining kidney function. Augmented renal clearance was defined as measured creatinine clearance of 130 mL/min per 1.73m2 or greater. A Poisson regression model was applied to identify predictors for augmented renal clearance. RESULTS: Augmented renal clearance prevalence was 30% and 35% in 103 abdominal and 129 trauma surgery patients, respectively. Younger age (abdominal cohort: relative risk, 0.963 (95% CI, 0.949-0.978); trauma cohort: relative risk, 0.971 [95% CI, 0.960-0.983]) and also for trauma surgery patients, male sex (relative risk, 1.808 [95% CI, 1.026 3.185]) were found to be independent predictors for augmented renal clearance. CONCLUSIONS: Augmented renal clearance is an underestimated phenomenon in adult non-critically ill surgery patients. Especially younger patients, and, in the subset of trauma surgery, males are prone to exhibit augmented renal clearance. Since augmented renal clearance is a risk factor for lower antimicrobial exposure, the impact of augmented renal clearance in relation to antimicrobial underexposure should be investigated in this population. LEVEL OF EVIDENCE: Prognostic/epidemiological study, level III. PMID- 27257708 TI - Elder abuse: Paucity of data hampers evidence-based injury prevention. PMID- 27257710 TI - Characteristics of ACS-verified Level I and Level II trauma centers: A study linking trauma center verification review data and the National Trauma Data Bank of the American College of Surgeons Committee on Trauma. AB - BACKGROUND: The Trauma Quality Improvement Project of the American College of Surgeons (ACS) has demonstrated variations in trauma center outcomes despite similar verification status. The purpose of this study was to identify structural characteristics of trauma centers that affect patient outcomes. METHODS: Trauma registry data on 361,187 patients treated at 222 ACS-verified Level I and Level II trauma centers were obtained from the National Trauma Data Bank of ACS. These data were used to estimate each center's observed-to-expected (O-E) mortality ratio with 95% confidence intervals using multivariate logistic regression analysis. De-identified data on structural characteristics of these trauma centers were obtained from the ACS Verification Review Committee. Centers in the lowest quartile of mortality based on O-E ratio (n = 56) were compared to the rest (n = 166) using Classification and Regression Tree (CART) analysis to identify institutional characteristics independently associated with high performing centers. RESULTS: Of the 72 structural characteristics explored, only 3 were independently associated with high-performing centers: annual patient visits to the emergency department of fewer than 61,000; proportion of patients on Medicare greater than 20%; and continuing medical education for emergency department physician liaison to the trauma program ranging from 55 and 113 hours annually. Each 5% increase in O-E mortality ratio was associated with an increase in total length of stay of one day (r = 0.25; p < 0.001). CONCLUSIONS: Very few structural characteristics of ACS-verified trauma centers are associated with risk-adjusted mortality. Thus, variations in patient outcomes across trauma centers are likely related to variations in clinical practices. LEVEL OF EVIDENCE: Therapeutic study, level III. PMID- 27257709 TI - Inhibition of histone deacetylase 6 restores intestinal tight junction in hemorrhagic shock. AB - BACKGROUND: We recently discovered that Tubastatin-A, a histone deacetylase (HDAC6) inhibitor, can improve survival in a rodent model of hemorrhagic shock (HS), but mechanisms remain poorly defined. In this study, we investigated whether Tubastatin-A could protect intestinal tight junction (TJ) in HS. METHODS: In an in-vivo study with Wistar-Kyoto rats, the rats underwent HS (40% blood loss) followed by Tubastatin-A (70 mg/kg) treatment, without fluid resuscitation. The experimental groups were (1) sham (no hemorrhage, no treatment), (2) control (hemorrhage, without treatment), and (3) treatment (hemorrhage with Tubastatin-A administration). Six hours after hemorrhage, ileum was harvested. Whole cell lysate were analyzed for acetylated alpha-tubulin (Ac-tubulin), total tubulin, acetylated histone 3 at lysine 9 (Ac-H3K9), beta-actin, claudin-3 and zonula occludens 1 (ZO-1) proteins by Western blot. Histological effects of Tubastatin-A on small bowel were examined. In an in-vitro study, human intestinal epithelial cells (Caco-2) were divided into three groups: (1) sham (normoxia), (2) control (anoxia, no treatment), and (3) treatment (anoxia, treatment with Tubastatin-A). After 12 hours in an anoxia chamber, the cells were examined for Ac-tubulin and Ac-H3K9, cellular viability, cytotoxicity, claudin-3 and ZO-1 protein expression, and transwell permeability study. RESULTS: Tubastatin-A treatment significantly attenuated HS-induced decreases of Ac-tubulin, Ac-H3K9, ZO-1 and claudin-3 proteins in small bowel in-vivo (p < 0.05). In cultured Caco-2 cells, anoxia significantly decreased cellular viability (p < 0.001) and increased cytotoxicity (p < 0.001) compared to the sham group, while Tubastatin-A treatment offered significant protection (p < 0.0001). Moreover, expression of claudin-3 was markedly decreased in vitro compared to the sham group, whereas this was significantly attenuated by Tubastatin-A (p < 0.05). Finally, anoxia markedly increased the permeability of Caco-2 monolayer cells (p < 0.05), while Tubastatin A significantly attenuated the alteration (p < 0.05). CONCLUSION: Inhibition of HDAC6 can induce Ac-tubulin and Ac-H3K9, promote cellular viability, and prevent the loss of intestinal tight junction proteins during HS and anoxia. PMID- 27257711 TI - Reduced need for extraperitoneal pelvic packing for severe pelvic fractures is associated with improved resuscitation strategies. AB - BACKGROUND: Extraperitoneal pelvic packing (EPP) was introduced at Oslo University Hospital Ulleval (OUHU) in 1994. Published studies from other institutions have advocated its application as a first-line therapy in lieu of angiography. Extraperitoneal pelvic packing is invasive with a high risk of complications, and its role remains an issue of discussion. In line with international trends, an updated massive hemorrhage protocol was implemented at OUHU in 2007. We hypothesized a decreased need for EPP owing to the major changes in resuscitation strategies. METHODS: Retrospective analysis of data from the OUH Trauma Registry and patient charts for the period 2002-2012 was performed. All pelvic fractures with Abbreviated Injury Severity (AIS) score of 3 or higher and/or transfused during the period before intensive care unit admission regardless of the pelvic AIS were included. The population was analyzed for trends and differences between 2002-2006 (P1) and 2007-2012 (P2). Further analysis was performed on the group of patients transfused five or more units of red blood cells (RBCs). RESULTS: We included 648 patients (P1, 297; P2, 351). There was no difference in median injury severity score, pelvic AIS, or age between the two periods. Median base deficit on admission was higher in P2 (4.2 vs 3.3 mmol/L; p < 0.01). The EPP rate decreased from P1 to P2 (17-10%; p < 0.01). A similar reduction in the angiography rate (15% vs 9%; p < 0.01) was observed, with a concomitant decrease in hemorrhage-related deaths (10% vs 5%; p = 0.01). The subgroup analysis of patients transfused five or more units of RBCs revealed significant increase in the use of plasma and platelets in P2. Multiple logistic regression models for the subgroup transfused five or more units of RBCs confirm the change in resuscitation strategy to be significantly associated with reduced EPP, and identifying admission in P2 to be associated with a 63% decreased odds ratio for EPP. CONCLUSIONS: The EPP and angiography rates for exsanguinating pelvic injuries have decreased with improved resuscitation strategies, reducing RBC requirements and hemorrhage-related deaths. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 27257712 TI - Double-Nanocarbon Synergistically Modified Na3V2(PO4)3: An Advanced Cathode for High-Rate and Long-Life Sodium-Ion Batteries. AB - An advanced cathode material, nitrogen-doped carbon-coated Na3V2(PO4)3 hybriding with multiwalled carbon nanotubes (CNTs) composite, namely double-nanocarbon synergistically modified Na3V2(PO4)3 of sodium ion battery, was fabricated through a simple sol-gel approach. According to the systemical analysis of experimental results on this composite structure, it is found that N-doping not only increases Na-ion migration velocity across the carbon-coated layer but also improves the electric conductivity of the carbon layer. More importantly, the CNTs 3D conducting network could significantly accelerate the electron transport between multiple particles of Na3V2(PO4)3, due to the intimate contacts between active materials and CNTs. Consenquently, the electrochemical properties of this double-nanocarbon-modified Na3V2(PO4)3 are significantly enhanced, especially the high-rate capability and long cycle life. For instance, its initial capacity of 94.5 mAh g(-1) at 0.2 C decreases to 70 mAh g(-1) at 70 C, and the capacity retention is 74%. Moreover, when dischage rate increases to a higher 30 C, the capacity retention is still as high as 87% after 300 cycles. PMID- 27257713 TI - Geometrical Spin Frustration of Unusually High Valence Fe(5+) in the Double Perovskite La2LiFeO6. AB - A double perovskite-structure oxide La2LiFeO6 with unusually high-valence Fe(5+) was synthesized using a high-pressure technique. The Li(+) and Fe(5+) ions at the B site in the rhombohedral R3 perovskite structure are ordered in a rock salt manner, and the resultant tetrahedral network of Fe(5+) gives geometrical spin frustration, which is consistent with a large frustration index f (|theta|/TN) ~ 10. Mg(2+) substitution for Li(+) produces Fe(4+) from some Fe(5+) and changes the magnetic properties. The Weiss temperature is increased from -119 to 21 K by the substitution of only 1%, significantly decreasing the frustration index. The geometrical frustration of the Fe(5+) spin sublattice cannot be tolerant for even a very small amount of Fe(4+) disturbance. PMID- 27257714 TI - Modelling cadmium contamination in paddy soils under long-term remediation measures: Model development and stochastic simulations. AB - A pollutant accumulation model (PAM) based on the mass balance theory was developed to simulate long-term changes of heavy metal concentrations in soil. When combined with Monte Carlo simulation, the model can predict the probability distributions of heavy metals in a soil-water-plant system with fluctuating environmental parameters and inputs from multiple pathways. The model was used for evaluating different remediation measures to deal with Cd contamination of paddy soils in Youxian county (Hunan province), China, under five scenarios, namely the default scenario (A), not returning paddy straw to the soil (B), reducing the deposition of Cd (C), liming (D), and integrating several remediation measures (E). The model predicted that the Cd contents of soil can lowered significantly by (B) and those of the plants by (D). However, in the long run, (D) will increase soil Cd. The concentrations of Cd in both soils and rice grains can be effectively reduced by (E), although it will take decades of effort. The history of Cd pollution and the major causes of Cd accumulation in soil were studied by means of sensitivity analysis and retrospective simulation. PMID- 27257715 TI - Evaluating the Free Energies of Solvation and Electronic Structures of Lithium Ion Battery Electrolytes. AB - Adaptive biasing force molecular dynamics simulations and density functional theory calculations were performed to understand the interaction of Li(+) with pure carbonates and ethylene carbonate (EC)-based binary mixtures. The most favorable Li carbonate cluster configurations obtained from molecular dynamics simulations were subjected to detailed structural and thermochemistry calculations on the basis of the M06-2X/6-311++G(d,p) level of theory. We report the ranking of these electrolytes on the basis of the free energies of Li-ion solvation in carbonates and EC-based mixtures. A strong local tetrahedral order involving four carbonates around the Li(+) was seen in the first solvation shell. Thermochemistry calculations revealed that the enthalpy of solvation and the Gibbs free energy of solvation of the Li(+) ion with carbonates are negative and suggested the ion-carbonate complexation process to be exothermic and spontaneous. Natural bond orbital analysis indicated that Li(+) interacts with the lone pairs of electrons on the carbonyl oxygen atom in the primary solvation sphere. These interactions lead to an increase in the carbonyl (C=O) bond lengths, as evidenced by a redshift in the vibrational frequencies [nu(C=O)] and a decrease in the electron density values at the C=O bond critical points in the primary solvation sphere. Quantum theory of atoms in molecules, localized molecular orbital energy decomposition analysis (LMO-EDA), and noncovalent interaction plots revealed the electrostatic nature of the Li(+) ion interactions with the carbonyl oxygen atoms in these complexes. On the basis of LMO-EDA, the strongest attractive interaction in these complexes was found to be the electrostatic interaction followed by polarization, dispersion, and exchange interactions. Overall, our calculations predicted EC and a binary mixture of EC/dimethyl carbonate to be appropriate electrolytes for Li-ion batteries, which complies with experiments and other theoretical results. PMID- 27257716 TI - Driving under the influence of non-alcohol drugs--An update. Part II: Experimental studies. AB - Experimental studies on the impairing effects of drugs of relevance to driving related performance published between 1998 and 2015 were reviewed. Studies with on-the-road driving, driving simulators, and performance tests were included for benzodiazepines and related drugs, cannabis, opioids, stimulants, GHB, ketamine, antihistamines, and antidepressants. The findings in these experimental studies were briefly discussed in relation to a review of epidemiological studies published recently. The studies mainly concluded that there may be a significant psychomotor impairment after using benzodiazepines or related drugs, cannabis, opioids, GHB, or ketamine. Low doses of central stimulants did not seem to cause impairment of driving behavior. PMID- 27257717 TI - Metabolism and toxicological analysis of synthetic cannabinoids in biological fluids and tissues. AB - Synthetic cannabinoids, which began proliferating in the United States in 2009, have gone through numerous iterations of modification to their chemical structures. More recent generations of compounds have been associated with significant adverse outcomes following use, including cognitive and psychomotor impairment, seizures, psychosis, tissue injury and death. These effects increase the urgency for forensic and public health laboratories to develop methods for the detection and identification of novel substances, and apply these to the determination of their metabolism and disposition in biological samples. This comprehensive review describes the history of the appearance of the drugs in the United States, discusses the naming conventions emerging to designate new structures, and describes the most prominent new compounds linked to the adverse effects now associated with their use. We review in depth the metabolic pathways that have been elucidated for the major members of each of the prevalent synthetic cannabinoid drug subclasses, the enzyme systems responsible for their metabolism, and the use of in silico approaches to assist in predicting and identifying the metabolites of novel compounds and drug subclasses that will continue to appear. Finally, we review and critique analytical methods applied to the detection of the drugs and their metabolites, including immunoassay screening, and liquid chromatography mass spectrometry confirmatory techniques applied to urine, serum, whole blood, oral fluid, hair, and tissues. PMID- 27257718 TI - Associations between psychological characteristics and indicators of metabolic syndrome among Chinese adults. AB - Current knowledge about the relationship between psychological characteristics and metabolic syndrome (MetS) components is limited in Asian populations. The purpose of this study is to investigate linkages between physiological markers of MetS and life satisfaction, hostility, and depression in Chinese adults. Secondary analyses were conducted using cross-sectional data from parents of randomly selected middle school students participating in a pilot study in Qingdao, China. Among 440 parents who consented to participate (237 women, 203 men), 368 provided valid responses in all three categories of psychological characteristics, and only those subjects were included in these analyses. General linear models and logistic regressions were run separately by gender, controlling for covariates. Among women, life satisfaction was inversely associated with triglyceride levels (p = .04), LDL-C (p < .01), risk of hypertriglyceridemia (OR[.53], p < .01), HDL-C (OR[.78], p = .03), and MetS (OR[.52], p = .03). No associations were found between life satisfaction and any psychological characteristics among men. Among women, hostility was positively associated with triglyceride level (p = .04) and risk of hypertriglyceridemia (OR[2.12], p < .05). Among men, hostility was positively associated with waist circumference (p = .04), waist-hip ratio (p < .05), and fasting plasma insulin (p < .01). Depression was not associated with any physiological measurement in either gender. These findings indicate that relationships exist between certain psychological characteristics and physiological indicators of MetS among Chinese adults, although there may be important differences between genders. PMID- 27257720 TI - Current Status of Bilateral Same-day Cataract Surgery. PMID- 27257719 TI - Cataract Surgery in the Setting of Corneal Pathology. PMID- 27257721 TI - Astigmatism Correction in Cataract Surgery: Toric Intraocular Lens Placement Versus Peripheral Corneal Relaxing Incisions. PMID- 27257722 TI - IOL Calculations in Short, Long, and Postrefractive Eyes. PMID- 27257723 TI - Toric Intraocular Lens Alignment: Manual Versus Automated Alignment Techniques for Toric IOLs. PMID- 27257724 TI - Refractive Enhancements After Cataract Surgery. PMID- 27257725 TI - Lens Placement in the Absence of Capsular Support: Scleral-fixated Versus Iris fixated IOL Versus ACIOL. PMID- 27257726 TI - Current Theories and Methods for Managing Negative Dysphotopsia. PMID- 27257727 TI - Cataract Drug Delivery Systems (Dropless vs. Nondropless Cataract Surgery). PMID- 27257728 TI - Refractive Surgery (SMILE vs. LASIK vs. Phakic IOL). PMID- 27257729 TI - Surgical Correction of Presbyopia: Lenticular, Corneal, and Scleral Approaches. PMID- 27257730 TI - Endothelial Keratoplasty: Descemet's Stripping Automated Endothelial Keratoplasty Versus Descemet's Membrane Endothelial Keratoplasty. PMID- 27257731 TI - LASIK Interface Complications: Pressure-induced Stromal Keratitis (PISK), Interface Fluid Syndrome (IFS) and Post-LASIK Edema-induced Keratopathy (PLEK). PMID- 27257732 TI - Phacoemulsification and Intraoperative Complications in 930 Patients With Uveitis. PMID- 27257734 TI - Preface: Controversies in Cataract, Refractive, and Corneal Surgery. PMID- 27257735 TI - Engineering a Transmembrane Nanopore Ion Channel from a Membrane Breaker Peptide. AB - Re-engineering nature's molecules is an ideal strategy to obtain explicit functionality such as synthetic molecular machines, yet novel strategies for producing engineered molecular channels are few. Here we report a peptide engineering strategy through sequence reversal, which we applied on the first transmembrane peptide of the mycobacteriophage membranoporin protein holin. We have successfully redesigned the membrane rupture property of this peptide to form specific nanopore ion channels. We report the structural characterization and electrophysiology measurements of a library of 28-residue engineered membrane peptides, with remarkable ion channel behavior. We further identify that key residues at the peptide terminus, the central proline, charge distribution, and hydropathy index of the peptide together contribute to the channel properties that we measure. Our sequence reversal strategy for peptide engineering to successfully obtain nanopore channels can pave the way for better biobased design of controlled nanopores, using only natural amino acids. PMID- 27257736 TI - The CYP2W1 enzyme: regulation, properties and activation of prodrugs. AB - CYP2W1 is expressed in the course of development of the gastrointestinal tract, silenced after birth in intestine and colon by epigenetic modifications, but activated following demethylation in colorectal cancer (CRC). The expression levels in CRC positively correlate with the degree of malignancy, are higher in metastases and are predictive of colon cancer survival. The CYP2W1 transcripts have been detected also in hepatocellular carcinoma, adrenocortical carcinoma, childhood rhabdomyosarcoma and breast cancer; however, here the protein expression remains to be confirmed. The CYP2W1 enzyme has an inverted orientation in the endoplasmic reticulum membrane, as compared to other cytochrome P450s and its immediate electron donor is unknown. Several lipid ligands have been proposed as endogenous substrates, among which retinol derivatives appear to have the highest affinities. However, the role of CYP2W1 in the endogenous and tumor localized metabolism of retinol derivatives has yet to be clarified. Indolines constitute high affinity exogenous compounds and specific chloromethylindolines have been shown to be activated by CYP2W1 into cytotoxic products in vitro and also in vivo, inhibiting the growth of human colon tumors in a mouse xenograft model. The CRC specific localization of CYP2W1 and its effective prodrug activation makes it a very promising target for future development of cancer therapeutics. PMID- 27257737 TI - Reporting of Randomized Controlled Trials With Statistically Nonsignificant Primary Outcomes Published in High-impact Surgical Journals. AB - OBJECTIVE: To determine the nature and frequency of distorted presentation or "spin" (ie, specific reporting strategies which highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or distract the reader from statistically nonsignificant results) in published reports of randomized controlled trials (RCTs) with statistically nonsignificant results for primary outcomes in surgical journals. BACKGROUND: Multiple reports have suggested that interpretation of RCT results in medical journals can be distorted by authors of published reports. METHODS: Using a defined search strategy, RCTs with clearly nonsignificant results for the primary outcome (P > 0.05) form 10 high-impact factor surgical journals (Annals of Surgery, Journal of Neurology, Neurosurgery and Psychiatry, Journal of Heart and Lung Transplantation, American Journal of Transplantation, British Journal of Surgery, Journal of Bone and Joint Surgery, Journal of the American College of Surgeons, Endoscopy, Archives of Surgery, and Liver transplantation), published between July 2013 to July 2015, were identified. Two reviewers independently appraised each selected article using a validated, standardized data abstraction form. RESULTS: In all, 110 eligible RCTs with nonsignificant primary outcomes were appraised. The title was reported with spin in 8 (7%) articles. Forty-four (40%) included abstracts and 39 (35%) main texts were classified as having spin in at least 1 section. The level of spin was high in 16 (14%) abstract and 19 (19%) main-text "Conclusions" sections. Twenty-five articles (23%) recommended the intervention of interest despite a nonsignificant primary outcome. There was no relationship between trial funding source, use of statistician and article section, and the presence of spin. CONCLUSIONS: In RCTs with statistically nonsignificant primary outcomes published in surgical journals, the reporting and interpretation of findings was frequently inconsistent with the results. PMID- 27257738 TI - Intention to Split Policy: A Successful Strategy in a Combined Pediatric and Adult Liver Transplant Center. AB - OBJECTIVE: The primary aim of this study is to evaluate the role of split liver transplantation (SLT) in a combined pediatric and adult liver transplant center. The secondary aim is to reflect on our clinical practice and discuss strategies to build a successful split program using an "intention to split policy." BACKGROUND: SLT is an established procedure to expand the organ pool and reduce wait list mortality; however, technical and logistic issues are limiting factors. METHODS: Prospectively collected data and outcomes of SLT procedures performed between November 1992 and March 2014 were analyzed retrospectively. To assess the effect of standardization and learning curve, the experience was divided into 2 time periods. RESULTS: Out of 3449 liver transplant procedures performed, 516(15%) were SLT. The recipients included 266 children (290 grafts; 56%) and 212 adults (226 grafts; 44%). The median donor age was 25(7-63 years) and the median weight was 70(22-111 kg). The cold and warm ischemic times improved significantly during the second period (SP) (2001-2014). With experience, there was a significant reduction in the biliary complications for both grafts. The introduction of "intention to split policy" resulted in a significantly increased usage of SLT. There was no mortality on the pediatric wait list for last 4 years. Over the last decade 65% of our pediatric transplants were SLT. The overall 1-, 5 , 10-year patient and graft survival of left graft recipients was 91%, 90%, and 89% and 90%, 87%, and 86%. For right grafts it was 87%, 82%, and 81% and 82%, 81%, and 79%, respectively. CONCLUSIONS: SLT is an effective surgical strategy to meet the demands in a combined adult and pediatric transplant center. Good outcomes can be achieved with a standardized technique. PMID- 27257740 TI - Risk drivers pose to themselves and other drivers by violating traffic rules. AB - OBJECTIVE: Violation of traffic rules is a major contributing factor in both crashes and fatalities in the United States. This study aims at quantifying risk that drivers pose to themselves and other drivers by violating traffic rules. METHOD: Crash data from 2010 to 2013 were gathered for the state of North Carolina. Descriptive analysis was carried out to identify frequent traffic violations and who were committing the traffic violations that resulted in crashes. A multinomial logit model was then developed to examine the relation between different traffic violations and driver injury severity. Additionally, odds ratios were estimated to identify the likelihood (probability) of severe or moderate injury to the driver and other drivers due to a driver violating a traffic rule that led to a crash. RESULTS: Exceeding the speed limit is more likely to result in severe injury compared to disregarding traffic signals. However, going the wrong way is more likely to result in severe injury to other drivers when compared to any other traffic violation. Driving under the influence of alcohol is 2 times more likely to result in severe injury than driving under the influence of drugs. These 2 traffic violations by a driver are almost equally likely to result in severe injury to other drivers. CONCLUSIONS: Drivers often perceive that violating traffic rules will not result in a crash or severe injury. However, the results from this study show that a majority of the traffic violations lead to severe injury to the violator as well as to other drivers. The findings from this study serve as documented evidence to educate drivers about the risk they pose to themselves and to other drivers by violating traffic rules and encourage the adaptation of safe driving behavior in order to contribute toward reaching the "zero traffic deaths" vision. They also help make policy changes pertaining to penalty points and fines for violating a traffic rule. PMID- 27257739 TI - Conditional knockout of retinal determination genes in differentiating cells in Drosophila. AB - Conditional gene knockout in postmitotic cells is a valuable technique which allows the study of gene function with spatiotemporal control. Surprisingly, in contrast to its long-term and extensive use in mouse studies, this technology is lacking in Drosophila. Here, we use a novel method for generating complete loss of eyes absent (eya) or sine oculis (so) function in postmitotic cells posterior to the morphogenetic furrow (MF). Specifically, genomic rescue constructs with flippase recognition target (FRT) sequences flanking essential exons are used to generate conditional null alleles. By removing gene function in differentiating cells, we show that eya and so are dispensable for larval photoreceptor differentiation, but are required for differentiation during pupal development. Both eya and so are necessary for photoreceptor survival and the apoptosis caused by loss of eya or so function is likely a secondary consequence of inappropriate differentiation. We also confirm their requirement for cone cell development and reveal a novel role in interommatidial bristle (IOB) formation. In addition, so is required for normal eye disc morphology. This is the first report of a knockout method to study eya and so function in postmitotic cells. This technology will open the door to a large array of new functional studies in virtually any tissue and at any stage of development or in adults. PMID- 27257741 TI - A 17-Year-Old Girl With Acute Onset of Hemiparesis. AB - The presentation of acute-onset hemiparesis in a teenager can be challenging and offers a wide differential diagnosis. We discuss the approach to the patient (which should begin with thorough history taking and physical examination) and advanced imaging as directed by the patient's signs and symptoms. We report the case of an otherwise well 17-year-old girl who presented to the pediatric emergency department with a 2-day history of left-sided weakness and difficulty ambulating. Her eventual diagnosis of Balo concentric sclerosis, a rare form of multiple sclerosis, is discussed. PMID- 27257742 TI - Evaporation of a Volatile Liquid Lens on the Surface of an Immiscible Liquid. AB - The evaporation behavior of toluene and hexane lenses on the surface of deionized (DI) water is studied. The toluene and hexane lenses during evaporation experience an advancing stage and a receding stage. There exists a significant difference of the evaporation behavior between the toluene lenses and the hexane lenses. The lifetime and largest diameter of both the toluene and hexane lenses increase with increasing the initial volume of the lenses. For the evaporation of the toluene lenses, the lifetime and largest diameter of the lenses decrease with increasing the temperature of DI water. The effect of the residual of the oil molecules on the evaporation of toluene lenses at a temperature of 21 degrees C is investigated via the evaporation of a series of consecutive toluene lenses being placed on the same position of the surface of DI water. The temporal evolution of the toluene lenses placed after the first toluene lens deviates significantly from that of the first toluene lens. Significant increase of the receding speed occurs at the dimensionless time in a range 0.7-0.8. PMID- 27257743 TI - Shiga toxin-producing Escherichia coli strains isolated from dairy products - Genetic diversity and virulence gene profiles. AB - Shiga toxin-producing Escherichia coli (STEC) are widely recognized as pathogens causing food borne disease. Here we evaluate the genetic diversity of 197 strains, mainly STEC, from serotypes O157:H7, O26:H11, O103:H2, O111:H8 and O145:28 and compared strains recovered in dairy products against strains from human, meat and environment cases. For this purpose, we characterized a set of reference-collection STEC isolates from dairy products by PFGE DNA fingerprinting and a subset of these by virulence-gene profiling. PFGE profiles of restricted STEC total DNA showed high genomic variability (0.9976 on Simpson's discriminatory index), enabling all dairy isolates to be differentiated. High throughput real-time PCR screening of STEC virulence genes were applied on the O157:H7 and O26:H11 STEC isolates from dairy products and human cases. The virulence gene profiles of dairy and human STEC strains were similar. Nevertheless, frequency-wise, stx1 was more prevalent among dairy O26:H11 isolates than in human cases ones (87% vs. 44%) while stx2 was more prevalent among O26:H11 human isolates (23% vs. 81%). For O157:H7 isolates, stx1 (0% vs. 39%), nleF (40% vs 94%) and Z6065 (40% vs 100%) were more prevalent among human than dairy strains. Our data point to differences between human and dairy strains but these differences were not sufficient to associate PFGE and virulence gene profiles to a putative lower pathogenicity of dairy strains based on their lower incidence in disease. Further comparison of whole-genome expression and virulence gene profiles should be investigated in cheese and intestinal tract samples. PMID- 27257744 TI - Bacterial quality and safety of packaged fresh leafy vegetables at the retail level in Finland. AB - Consumption of packaged fresh leafy vegetables, which are convenient ready-to-eat products, has increased during the last decade. The number of foodborne outbreaks associated with these products has concurrently increased. In our study, (1) label information, (2) O2/CO2 composition, (3) bacterial quality and (4) safety of 100 fresh leafy vegetables at the retail level were studied in Finland during 2013. Bacterial quality was studied using aerobic bacteria (AB) and coliform bacteria (CB) counts, and searching for the presence of Escherichia coli, Listeria and Yersinia. The safety was studied by the presence of Salmonella, ail positive Yersinia, stx-positive E. coli (STEC) and Listeria monocytogenes using PCR and culturing. Important label information was unavailable on several packages originating from different companies. The packaging date was missing on all packages and the date of durability on 83% of the packages. Storage temperature was declared on 62% of the packages and 73% of the packages contained information about prewashing. The batch/lot number was missing on 29% of the packages. Very low oxygen (O2) (<1%) and elevated carbon dioxide (CO2) (2-22%) concentrations were measured in all packages labelled to contain a protective atmosphere. O2 and CO2 concentrations varied widely in the rest of the packages. AB and CB counts were high in the leafy vegetable samples varying between 6.2 and 10.6 and 4.2-8.3logcfu/g, respectively. In most of the samples, the AB and CB counts exceeded 10(8) and 10(6)cfu/g, respectively. A positive correlation was observed between the AB and CB counts. E. coli was isolated from 15% of the samples and Yersinia from 33%. L. monocytogenes was isolated from two samples and ail-positive Y. enterocolitica in one. Using PCR, STEC was detected in seven samples, and Salmonella and ail-positive Y. enterocolitica in two samples each. The AB and CB mean values of products originating from different companies varied widely. High AB and CB counts and pathogenic bacteria were detected in ready-to eat products not needing washing before use. Our study shows that the bacterial quality and safety of packaged fresh leafy vegetables is poor and label information on the packages is inadequate. More studies are needed concerning the impact of a protective atmosphere on bacterial growth, and the impact of washing for removing bacteria. PMID- 27257745 TI - Elucidation of enterotoxigenic Bacillus cereus outbreaks in Austria by complementary epidemiological and microbiological investigations, 2013. AB - Identifying Bacillus cereus as the causative agent of a foodborne outbreak still poses a challenge. We report on the epidemiological and microbiological investigation of three outbreaks of food poisoning (A, B, and C) in Austria in 2013. A total of 44% among 32 hotel guests (A), 22% among 63 employees (B) and 29% among 362 residents of a rehab clinic (C) fell sick immediately after meal consumption. B. cereus isolated from left overs or retained samples from related foods were characterized by toxin gene profiling, and molecular typing using panC sequencing and M13-PCR typing (in outbreak A and C). We identified two B. cereus strains in outbreak A, and six B. cereus strains, each in outbreak B and C; we also found Staphylococcus aureus and staphylococcal enterotoxins in outbreak A. The panC sequence based phylogenetic affiliation of the B. cereus strains, together with findings of the retrospective cohort analyses, helped determining their etiological role. Consumption of a mashed potatoes dish in outbreak A (RR: infinity), a pancake strips soup in outbreak B (RR 13.0; 95% CI 1.8-93.0) and for outbreak C of a fruit salad (RR 1.50; 95% CI 1.09-2.00), deer ragout (RR: 1.99; 95% CI 1.23-3.22) and a cranberry/pear (RR 2.46; 95% CI 1.50-4.03)were associated with increased risk of falling sick. An enterotoxigenic strain affiliated to the phylogenetic group with the highest risk of food poisoning was isolated from the creme spinach and the strawberry buttermilk, and also from the stool samples of the one B. cereus positive outbreak case-patient, who ate both. Our investigation of three food poisoning outbreaks illustrates the added value of a combined approach by using epidemiological, microbiological and genotyping methods in identifying the likely outbreak sources and the etiological B. cereus strains. PMID- 27257746 TI - Virulence factors in fungal pathogens of man. AB - Human fungal pathogens are a commonly underestimated cause of severe diseases associated with high morbidity and mortality. Like other pathogens, their survival and growth in the host, as well as subsequent host damage, is thought to be mediated by virulence factors which set them apart from harmless microbes. In this review, we describe and discuss commonly employed strategies for fungal survival and growth in the host and how these affect the host-fungus interactions to lead to disease. While many of these strategies require host-specific virulence factors, more generally any fitness factor which allows growth under host-like conditions can be required for pathogenesis. Furthermore, we briefly summarize how different fungal pathogens are thought to damage the host. We find that in addition to a core of common activities relevant for growth, different groups of fungi employ different strategies which in spite of (or together with) the host's response can lead to disease. PMID- 27257747 TI - Sleep and Productivity Benefits of Digital Cognitive Behavioral Therapy for Insomnia: A Randomized Controlled Trial Conducted in the Workplace Environment. AB - OBJECTIVE: Evaluating digital cognitive behavioral therapy (dCBT) for insomnia in a workplace environment. METHODS: Within a randomized controlled trial in a Fortune 500 company, we randomized 270 self-identified poor sleepers [180 M/90 F: mean age 33.6 years (23 to 56 years)] to dCBT (n = 135) or waiting list (WL, n = 135). dCBT comprised six online sessions delivered by an animated therapist. Major assessments were at baseline and posttreatment. RESULTS: Sleep Condition Indicator (SCI) scores were significantly higher for the dCBT group [interaction term: F (1,485) = 15.63, P < 0.0001], representing Cohen's d of 1.10 following dCBT (d = 0.34 for WL). On the Work Productivity and Impairment questionnaire, "presenteeism" demonstrated significant improvements following dCBT [F(1,485) = 10.99, P = 0.001: d = 0.64 for dCBT, d = 0.09 for WL]. Effects for "abseenteeism" failed to reach statistical significance (P = 0.101). CONCLUSIONS: dCBT is effective in improving sleep and work-based productivity in adults with insomnia. PMID- 27257748 TI - Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits. AB - OBJECTIVE: Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. METHOD: Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. RESULTS: Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). DISCUSSION: Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). PMID- 27257749 TI - Phytomass change in natural phytocenosis as an indicator of technogenic pollution of soils with heavy metals. AB - This study considered the possibility of using plant community phytomass for the assessment of soil pollution with heavy metals (HM) from industrial wastes. The three-year-long field experiment was run under the regional natural meadow vegetation; the polymetallic galvanic slime was used as an industrial waste contaminant. It is shown that soil contamination primarily causes decrease of phytomass in the growing phytocenosis. The vegetation experiments determined nonlinear dependence of cultivated and wild plant biomass on the level of soil contamination; it is described by the equations of logistic and Gaussian regression. In the absence of permanent contaminants, the soil is self-cleaned over time. It reproduces phytomass mainly due to the productivity increase of the most pollution-tolerant species in the remaining phytocenosis. This phenomenon is defined as environmental hysteresis. Soil pollution by industrial waste leads to the loss of plant biodiversity. The research shows that the study of the HM impact on ecosystems is expedient given the consideration of the "soil phytocenosis-pollutant" complex in the "dose-response" aspect. The reaction of phytocenosis on HM showing decline in phytomass leads to serious limitations in the choice of accumulating plants, because the adsorbed HM are rejected through phytomass. PMID- 27257750 TI - The roles of gender and personality factors in vandalism and scrawl-graffiti among Swedish adolescents. AB - A total of 360 upper secondary school students in Sweden were divided into three grouping variables: gender (male, female), vandalism (involved, not involved), and scrawl-graffiti (involved, not involved). Relevant to the discussion of whether or not scrawl-graffiti may be construed as vandalism or art, the aim of the study was to explore whether or not personality factors known to be linked to vandalism in general (such as impulsivity, affectivity, emotional disability, and optimism) are related also to involvement in scrawl-graffiti, and, furthermore, how the gender factor relates to vandalism and scrawl-graffiti, respectively. The analysis showed that impulsiveness was a significant variable related to vandalism as well as to scrawl-graffiti. Further analysis indicated that vandalism was predicted by non-planning impulsiveness whereas scrawl-graffiti was predicted by motor impulsiveness. Analyses showed also that there were significant gender differences related to both vandalism and scrawl-graffiti, whereby male participants were significantly more involved in vandalism than female participants, while the latter were significantly more involved in scrawl graffiti than the former. PMID- 27257752 TI - Treating Liver Fibrosis: (Re)Programmed to Succeed. AB - Two papers (Rezvani et al., 2016; Song et al., 2016) in this issue of Cell Stem Cell use transcription-factor-mediated reprogramming to convert liver myofibroblasts into hepatocyte-like cells in mice. Moreover, murine models of fibrotic and cholestatic liver injury were used to demonstrate that this approach has potential for treatment of liver cirrhosis. PMID- 27257751 TI - Dynamic cell-matrix interactions modulate microbial biofilm and tissue 3D microenvironments. AB - Microbial biofilms and most eukaryotic tissues consist of cells embedded in a three-dimensional extracellular matrix. This matrix serves as a scaffold for cell adhesion and a dynamic milieu that provides varying chemical and physical signals to the cells. Besides a vast array of specific molecular components, an extracellular matrix can provide locally heterogeneous microenvironments differing in porosity/diffusion, stiffness, pH, oxygen and metabolites or nutrient levels. Mechanisms of matrix formation, mechanosensing, matrix remodeling, and modulation of cell-cell or cell-matrix interactions and dispersal are being revealed. This perspective article aims to identify such concepts from the fields of biofilm or eukaryotic matrix biology relevant to the other field to help stimulate new questions, approaches, and insights. PMID- 27257753 TI - Fat Decisions: Leptin Regulates Bone versus Fat in the Marrow. AB - Leptin is an adipocyte-derived hormone involved in energy sensing. In this issue of Cell Stem Cell, Yue et al. (2016) show that leptin is a physiologic signal that acts directly on Leptin-Receptor-expressing mesenchymal stromal cells in adult bone marrow to influence their lineage allocation in vivo, inhibiting bone formation and inducing marrow adipogenesis. PMID- 27257754 TI - Tumor Organoids Fill the Niche. AB - Organoid technologies have significant potential as effective patient avatars. Fujii et al. (2016) and van de Wetering et al. (2015) derive biobanks of colorectal tumor and matching normal organoids and identify associations between tumor subtype, oncogenic drivers, gene-drug interactions, and varying niche requirements for tumor organoid growth, engraftment, and metastasis. PMID- 27257755 TI - Retinas in a Dish Peek into Inherited Retinal Degeneration. AB - Human retinal degeneration can cause blindness, and the lack of relevant model systems has made identifying underlying mechanisms challenging. Parfitt et al. (2016) generate three-dimensional retinal tissue from patient-derived induced pluripotent stem cells to identify how CEP290 mutations cause retinal degeneration, and show an antisense approach can correct disease-associated phenotypes. PMID- 27257756 TI - Circulating Monocytes in between the Gut and the Mind. AB - Hippocampal neurogenesis is affected throughout life by factors external to the brain, including what we eat, our gut microbiota, and the immune system. However, the mechanisms that link microbiota to neurogenesis are still puzzling. Now in Cell Reports, Mohle et al. (2016) attribute a role to Ly6C(hi) monocytes in this gut-immune-brain axis. PMID- 27257757 TI - Growing Kidney Tissue from Stem Cells: How Far from "Party Trick" to Medical Application? AB - The successful generation of kidney-like structures from human pluripotent stem cells, although slower to come than other tissue types, brings the hope of new therapies. While the demand for alternative treatments for kidney failure is acute, huge challenges remain to move these exciting but preliminary results toward clinical use. PMID- 27257758 TI - Closing in on Mass Production of Mature Human Beta Cells. AB - Human pluripotent stem cell differentiation protocols based on mimicking developmental pathways are getting close to generating fully fledged pancreatic endocrine cells, including insulin-producing beta cells. However, challenges remain in identifying pathways to trigger the attainment of robust glucose responsiveness that occurs postnatally in beta cells. PMID- 27257759 TI - Human Pluripotent Stem Cells: Myths and Future Realities for Liver Cell Therapy. AB - The severe shortage of organ donors for treating patients with liver disease has prompted in vitro efforts to produce the main functional cells of the liver: hepatocyte-like cells (Hep cells). We consider the key challenges posed by various stem cell technologies and liver pathologies for developing clinically useful Hep cells. PMID- 27257761 TI - Gametogenesis from Pluripotent Stem Cells. AB - The germ cell lineage originates early in development and undergoes a series of complex developmental processes that culminate in the generation of fully matured gametes, the spermatozoa and the oocytes. Remarkably, researchers have been recapitulating these developmental pathways using mouse and human pluripotent stem cells (PSCs). With further studies, including those involving non-human primate models, human gametogenesis may be fully reconstituted from PSCs, which would profoundly facilitate our understanding of human germ cell development and infertility. Here we discuss groundbreaking studies that lay the foundation for this achievement, the current state of the field, and challenges for deriving gametes from hPSCs. PMID- 27257760 TI - Engineering Hematopoietic Stem Cells: Lessons from Development. AB - Cell engineering has brought us tantalizingly close to the goal of deriving patient-specific hematopoietic stem cells (HSCs). While directed differentiation and transcription factor-mediated conversion strategies have generated progenitor cells with multilineage potential, to date, therapy-grade engineered HSCs remain elusive due to insufficient long-term self-renewal and inadequate differentiated progeny functionality. A cross-species approach involving zebrafish and mammalian systems offers complementary methodologies to improve understanding of native HSCs. Here, we discuss the role of conserved developmental timing processes in vertebrate hematopoiesis, highlighting how identification and manipulation of stage-specific factors that specify HSC developmental state must be harnessed to engineer HSCs for therapy. PMID- 27257762 TI - Stem Cell Models of Human Brain Development. AB - Recent breakthroughs in pluripotent stem cell technologies have enabled a new class of in vitro systems for functional modeling of human brain development. These advances, in combination with improvements in neural differentiation methods, allow the generation of in vitro systems that reproduce many in vivo features of the brain with remarkable similarity. Here, we describe advances in the development of these methods, focusing on neural rosette and organoid approaches, and compare their relative capabilities and limitations. We also discuss current technical hurdles for recreating the cell-type complexity and spatial architecture of the brain in culture and offer potential solutions. PMID- 27257765 TI - Stark Spectroscopy of Rubrene. I. Electroabsorption Spectroscopy and Molecular Parameters. AB - Electroabsorption spectroscopy investigation and the determination of molecular parameters for rubrene dispersed in a poly(methyl methacrylate) (PMMA) matrix are reported. The features of the band system in the absorption spectrum in PMMA are analogous to those in solutions. The changes in the electric dipole moment and the polarizability between the excited and ground states are determined from analysis of the Stark effect in the absorption band. The change in the transition dipole moment in the presence of an external electric field is also observed. Although rubrene is predicted to be classified as a nonpolar molecule, there is a contribution of the difference in the electric dipole moment between the excited and ground states to the electroabsorption spectrum. The origin of the nonzero difference in the electric dipole moment is argued. Stark fluorescence spectroscopy investigation is reported in Part II of this series. PMID- 27257763 TI - In Vivo Hepatic Reprogramming of Myofibroblasts with AAV Vectors as a Therapeutic Strategy for Liver Fibrosis. AB - Liver fibrosis, a form of scarring, develops in chronic liver diseases when hepatocyte regeneration cannot compensate for hepatocyte death. Initially, collagen produced by myofibroblasts (MFs) functions to maintain the integrity of the liver, but excessive collagen accumulation suppresses residual hepatocyte function, leading to liver failure. As a strategy to generate new hepatocytes and limit collagen deposition in the chronically injured liver, we developed in vivo reprogramming of MFs into hepatocytes using adeno-associated virus (AAV) vectors expressing hepatic transcription factors. We first identified the AAV6 capsid as effective in transducing MFs in a mouse model of liver fibrosis. We then showed in lineage-tracing mice that AAV6 vector-mediated in vivo hepatic reprogramming of MFs generates hepatocytes that replicate function and proliferation of primary hepatocytes, and reduces liver fibrosis. Because AAV vectors are already used for liver-directed human gene therapy, our strategy has potential for clinical translation into a therapy for liver fibrosis. PMID- 27257764 TI - Subunit Arrangement in GpsB, a Regulator of Cell Wall Biosynthesis. AB - GpsB, a key regulator of cell division in Gram-positive bacteria, interacts with a key peptidoglycan synthase at the cell division septum, the penicillin binding protein PBP1 (a.k.a. PonA). Bacillus subtilis GpsB has been reported to interact with other components of the cell division machinery, including EzrA, MreC, and PrkC. In this study, we report an analysis of the arrangement of subunits in Listeria monocytogenes GpsB by small-angle X-ray scattering. The resulting model has an elongated shape with residues critical for interaction with PBP1 and the cell membrane clustered at one end of the molecule. Mutations that destabilize the hexameric assembly of the wild-type protein have a gpsB null phenotype, indicating that oligomerization is critical for the correct function of GpsB. We suggest a model in which a single GpsB hexamer can interact with multiple PBP1 molecules and can therefore influence the arrangement of PBP1 molecules within the cell division machinery, a dynamic multiprotein complex called the divisome, consistent with a role for GpsB in modulating the synthesis of the cell wall. PMID- 27257766 TI - Imaging Manifestations of Hematologic Diseases with Renal and Perinephric Involvement. AB - The kidneys and perinephric tissues can be affected by a variety of hematologic disorders, which usually occur in the setting of multisystem involvement. In many of these disorders, imaging is used to evaluate the extent of disease, guide biopsy, and/or monitor disease activity and patient response to therapy. Lymphoma, leukemia, and multiple myeloma commonly manifest as multiple parenchymal or perinephric lesions. Erdheim-Chester disease and Rosai-Dorfman disease, rare forms of multisystemic histiocytosis, are often identified as perinephric and periureteral masses. Renal abnormalities depicted at imaging in patients with sickle cell disease include renal enlargement, papillary necrosis, and renal medullary carcinoma. Sickle cell disease, along with other causes of intravascular hemolysis, can also lead to hemosiderosis of the renal cortex. Thrombosis of renal veins is sometimes seen in patients with coagulation disorders but more often occurs in association with certain malignancies and nephrotic syndrome. Immunoglobulin G4-related sclerosing disease is another multisystem process that often produces focal renal lesions, seen along with involvement of more characteristic organs such as the pancreas. Perinephric lesions with calcifications should raise the possibility of secondary amyloidosis, especially in patients with a history of lymphoma and multiple myeloma. Although the imaging patterns of renal and perinephric involvement are usually not specific for a single entity, and the same entity can manifest with different or overlapping patterns, familiarity with these patterns and key clinical and histopathologic features may help to narrow the differential diagnosis and determine the next step of care. ((c))RSNA, 2016. PMID- 27257767 TI - Imaging of the Patient with Thoracic Outlet Syndrome. AB - Patients with symptoms from compression of the neurovascular bundle in the thoracic outlet are described as having thoracic outlet syndrome (TOS), which is best thought of as three conditions classified according to which structures are involved. The purpose of this article is to review the role of imaging in evaluation of patients with TOS, beginning with diagnosis and extending through postoperative management. While diagnosis of TOS still rests on the patient's presenting history and physical examination, imaging examinations are helpful in supporting the diagnosis, delineating abnormal anatomy, determining which structures are compressed, identifying the site of compression, and excluding other diagnoses. Magnetic resonance imaging is the noninvasive imaging modality of choice in evaluating patients with suspected TOS, but computed tomography also plays an important role, particularly in delineating bone anatomy. Evidence of vascular damage is required to make the diagnosis of TOS at imaging. Dynamic compression of the axillosubclavian vessels at the thoracic outlet can be a finding supportive of the diagnosis of TOS but is not a stand-alone diagnostic criterion, as it can be seen in patients without TOS. As diagnosis and treatment of TOS increase, radiologists will increasingly encounter the TOS patient after decompression surgery. Recognition of the expected postoperative appearance of these patients is critical, as is an understanding of the imaging findings of potential short- and long-term complications. ((c))RSNA, 2016. PMID- 27257768 TI - Tetranorlabdane Diterpenoids from the Deep Sea Sediment-Derived Fungus Aspergillus wentii SD-310. AB - Two new tetranorlabdane diterpenoids, asperolides D (1) and E (2), along with six related known congeners (3-8), were isolated and identified from the culture extract of the deep sea sediment-derived fungus Aspergillus wentii SD-310. The structures of these compounds were established on the basis of spectroscopic interpretation, and the skeleton and absolute configurations of asperolides D (1) and E (2) were determined by X-ray crystallographic analysis. Compounds 1 and 2 were evaluated for their cytotoxic activity against seven tumor cell lines and antibacterial activity against two human and eight aquatic pathogens. PMID- 27257769 TI - Pharmacokinetics of hERG Channel Blocking Voacangine in Wistar Rats Applying a Validated LC-ESI-MS/MS Method. AB - Herbal preparations from Voacanga africana are used in West and Central African folk medicine and are also becoming increasingly popular as a legal high in Europe. Recently, the main alkaloid voacangine was found to be a potent human ether-a-go-go-related gene channel blocker in vitro. Blockage of this channel might imply possible cardiotoxicity. Therefore, the aim of this study was to characterise voacangine in vivo to assess its pharmacokinetics and to estimate if further studies to investigate its cardiotoxic risk are required. Male Wistar rats received different doses of voacangine as a pure compound and as a hydro ethanolic extract of V. africana root bark with a quantified amount of 9.71 % voacangine. For the obtained data, a simultaneous population pharmacokinetics model was successfully developed, comprising a two-compartment model for i. v. dosing and a one-compartmental model with two first-order absorption rates for oral dosing. The absolute bioavailability of voacangine was determined to be 11 13 %. Model analysis showed significant differences in the first absorption rate constant for voacangine administered as a pure compound and voacangine from the extract of V. africana. Taking into account the obtained low bioavailability of voacangine, its cardiotoxic risk might be neglectable in healthy consumers, but may have a serious impact in light of drug/drug interactions and impaired health conditions. PMID- 27257779 TI - Why Population Health and Palliative Care Need Each Other. PMID- 27257780 TI - Is patient flow more efficient in Urgent Care Collaborations? AB - OBJECTIVE: Emergency Departments and out-of-hours General Practitioner services collaborate increasingly in Urgent Care Collaborations (UCCs) by sharing one combined entrance and joint triage. The aim of this study is to examine the difference between UCCs and providers who operate separately with respect to the efficiency of patient flow. METHODS: This study had a cross-sectional observational design comparing three regions with UCC with three regions with usual care. Outcome measures were efficiency of patient flow, defined as a reducing length of stay (LOS), waiting time (WT) and the mean number of handovers. Data were obtained from electronic medical records. RESULTS: LOS (median 34:00 vs. 38:52 min) and WT (median 14:00 vs. 18:43 min) were statistically significantly longer in UCCs compared with usual care. This difference is mainly explained by the prolonged LOS and WT for consulting a General Practitioner. The mean number of interunit handovers was larger in UCCs. CONCLUSION: The results indicate that, on average, UCCs do not enhance the efficiency of patient flow. The median LOS and WT are longer in UCCs and more handovers occur in UCCs compared with usual care. PMID- 27257781 TI - Unraveling the aggregation propensity of human insulin C-peptide. AB - Over the last 20 years, proinsulin C-peptide emerged as an important player in various biological events. Much time and effort has been spent in exploring all functional features of C-peptide and recording its implications in Diabetes mellitus. Only a few studies, though, have addressed C-peptide oligomerization and link this procedure with Diabetes. The aim of our work was to examine the aggregation propensity of C-peptide, utilizing Transmission Electron Microscopy, Congo Red staining, ATR-FTIR, and X-ray fiber diffraction at a 10 mg ml-1 concentration. Our experimental work clearly shows that C-peptide self-assembles into amyloid-like fibrils and therefore, the aggregation propensity of C-peptide is a characteristic novel feature that should be related to physiological and also pathological conditions. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 108: 1-8, 2017. PMID- 27257782 TI - Crystal-Field and Covalency Effects in Uranates: An X-ray Spectroscopic Study. AB - The electronic structure of U(V) - and U(VI) -containing uranates NaUO3 and Pb3 UO6 was studied by using an advanced technique, namely X-ray absorption spectroscopy (XAS) in high-energy-resolution fluorescence-detection (HERFD) mode. Due to a significant reduction in core-hole lifetime broadening, the crystal field splittings of the 5f shell were probed directly in HERFD-XAS spectra collected at the U 3d edge, which is not possible by using conventional XAS. In addition, the charge-transfer satellites that result from U 5f-O 2p hybridization were clearly resolved. The crystal-field parameters, 5f occupancy, and degree of covalency of the chemical bonding in these uranates were estimated by using the Anderson impurity model by calculating the U 3d HERFD-XAS, conventional XAS, core to-core (U 4f-3d transitions) resonant inelastic X-ray scattering (RIXS), and U 4f X-ray photoelectron spectra. The crystal field was found to be strong in these systems and the 5f occupancy was determined to be 1.32 and 0.84 electrons in the ground state for NaUO3 and Pb3 UO6 , respectively, which indicates a significant covalent character for these compounds. PMID- 27257783 TI - In vivo (31) P MRS assessment of intracellular NAD metabolites and NAD(+) /NADH redox state in human brain at 4 T. AB - NAD(+) and NADH play key roles in cellular respiration. Intracellular redox state defined by the NAD(+) /NADH ratio (RX) reflects the cellular metabolic and physiopathological status. By taking advantage of high/ultrahigh magnetic field strengths, we have recently established a novel in vivo (31) P MRS-based NAD assay for noninvasive and quantitative measurements of intracellular NAD concentrations and redox state in animal and human brains at 16.4 T, 9.4 T and 7 T. To explore its potential for clinical application, in this study we investigated the feasibility of assessing the NAD metabolism and redox state in human brain at a lower field of 4 T by incorporating the (1) H-decoupling technique with the in vivo (31) P NAD assay. The use of (1) H decoupling significantly narrowed the linewidths of NAD and alpha-ATP resonances, resulting in higher sensitivity and better spectral resolution as compared with the (1) H coupled (31) P spectrum. These improvements made it possible to reliably quantify cerebral NAD concentrations and RX, consistent with previously reported results obtained from similar age human subjects at 7 T. In summary, this work demonstrates the capability and utility of the (1) H-decoupled (31) P MRS-based NAD assay at lower field strength; thus, it opens new opportunities for studying intracellular NAD metabolism and redox state in human brain at clinical settings. This conclusion is supported by the simulation results, indicating that similar performance and reliability as observed at 4T can be achieved at 3 T with the same signal-to-noise ratio. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27257785 TI - Quality of life in epilepsy in Bhutan. AB - PURPOSE: To assess the quality of life in epilepsy (QOLIE) among adults in the lower middle-income country of Bhutan and assess the potential demographic and clinical associations with better QOLIE. METHODS: People with clinically diagnosed epilepsy were prospectively enrolled at the Jigme Dorji Wangchuck National Referral Hospital in Thimphu (2014-2015). Regression models were constructed to assess the potential impact of age, sex, residence in the capital city, wealth quintile, educational attainment, seizure in the prior year, seizures with loss of consciousness, self-reported stigma score, and need for multiple antiepileptic drugs. RESULTS: The mean Bhutanese QOLIE-31 score among 172 adults (mean age 31.1 years, 93 female) was 48.9/100+/-17.7. Younger age, lower educational attainment level, and increased self-perceived stigma were each observed to have an independent, negative association with QOLIE (p<0.05), while a patient's wealth quintile, sex, seizure frequency, seizure type and number of antiepileptic drugs were not. Education appeared to be most strongly associated with QOL at the high school and college levels. CONCLUSIONS: There are potentially modifiable associations with low QOLIE. Addressing the educational level and self-perceived stigma of PWE may have an especial impact. The low QOLIE in Bhutan may reflect cultural approaches to epilepsy, health services, or other factors including those outside of the health sector. PMID- 27257786 TI - How a Thermally Unstable Metal Hydrido Complex Can Yield High Catalytic Activity Even at Elevated Temperatures. AB - Despite their instability in ethereal solvents, organotitanium hydride catalysts are successfully employed in catalysis at moderate to high temperatures (110 degrees C), even in the presence of alcohols. It is shown computationally (bond dissociation energy (BDE) analysis and energetic profile for regeneration) and experimentally (EPR studies and kinetic studies), with the specific example of hydrodefluorination (HDF), that despite the long standing belief, regeneration of Ti-H bonds from Ti-F bonds using silanes is endergonic. The resulting low concentration of Ti-H species is crucial for the catalytic stability of those systems. The resting state in the catalysis is a Ti-F species. The most promising silanes for regeneration are not the ones that have the strongest Si-F bond, but the ones that show the largest difference in Si-F and Si-H BDEs. PMID- 27257784 TI - Evidencing a place for the hippocampus within the core scene processing network. AB - Functional neuroimaging studies have identified several "core" brain regions that are preferentially activated by scene stimuli, namely posterior parahippocampal gyrus (PHG), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS). The hippocampus (HC), too, is thought to play a key role in scene processing, although no study has yet investigated scene-sensitivity in the HC relative to these other "core" regions. Here, we characterised the frequency and consistency of individual scene-preferential responses within these regions by analysing a large dataset (n = 51) in which participants performed a one-back working memory task for scenes, objects, and scrambled objects. An unbiased approach was adopted by applying independently-defined anatomical ROIs to individual-level functional data across different voxel-wise thresholds and spatial filters. It was found that the majority of subjects had preferential scene clusters in PHG (max = 100% of participants), RSC (max = 76%), and TOS (max = 94%). A comparable number of individuals also possessed significant scene-related clusters within their individually defined HC ROIs (max = 88%), evidencing a HC contribution to scene processing. While probabilistic overlap maps of individual clusters showed that overlap "peaks" were close to those identified in group-level analyses (particularly for TOS and HC), inter-individual consistency varied across regions and statistical thresholds. The inter-regional and inter-individual variability revealed by these analyses has implications for how scene-sensitive cortex is localised and interrogated in functional neuroimaging studies, particularly in medial temporal lobe regions, such as the HC. Hum Brain Mapp 37:3779-3794, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27257787 TI - Cystathionine-beta-synthase inhibition for colon cancer: Enhancement of the efficacy of aminooxyacetic acid via the prodrug approach. AB - Colon cancer cells contain high levels of cystathionine-beta-synthase (CBS). Its product, hydrogen sulfide (H2S) promotes the growth and proliferation of colorectal tumor cells. In order to improve the antitumor efficacy of the prototypical CBS inhibitor aminooxyacetic acid (AOAA), we have designed and synthesized YD0171, a methyl ester derivative of AOAA. The antiproliferative effect of YD0171 exceeded the antiproliferative potency of AOAA in HCT116 human colon cancer cells. The esterase inhibitor paraoxon prevented the cellular inhibition of CBS activity by YD0171. YD0171 suppressed mitochondrial respiration and glycolytic function and induced G0/G1 arrest, but did not induce tumor cell apoptosis or necrosis. Metabolomic analysis in HCT116 cells showed that YD0171 affects multiple pathways of cell metabolism. The efficacy of YD0171 as an inhibitor of tumor growth was also tested in nude mice bearing subcutaneous HCT116 cancer cell xenografts. Animals were treated via subcutaneous injection of vehicle, AOAA (1, 3 or 9 mg/kg/day) or YD0171 (0.1, 0.5 or 1 mg/kg/day) for 3 weeks. Tumor growth was significantly reduced by 9 mg/kg/day AOAA, but not at the lower doses. YD0171 was more potent: tumor volume was significantly inhibited at 0.5 and 1 mg/kg/day. Thus, the in vivo efficacy of YD0171 is 9-times higher than that of AOAA. YD0171 (1 mg/kg/day) attenuated tumor growth and metastasis formation in the intracecal HCT116 tumor model. YD0171 (3 mg/kg/day) also reduced tumor growth in patient-derived tumor xenograft (PDTX) bearing athymic mice. YD0171 (3 mg/kg/day) induced the regression of established HCT116 tumors in vivo. A 5-day safety study in mice demonstrated that YD0171 at 20 mg/kg/day (given in two divided doses) does not increase plasma markers of organ injury, nor does it induce histological alterations in the liver or kidney. YD0171 caused a slight elevation in plasma homocysteine levels. In conclusion, the prodrug approach improves the pharmacological profile of AOAA; YD0171 represents a prototype for CBS inhibitory anticancer prodrugs. By targeting colorectal cancer bioenergetics, an emerging important hallmark of cancer, the approach exemplified herein may offer direct translational opportunities. PMID- 27257788 TI - Identification of the MicroRNA Repertoire in TLR-Ligand Challenged Bubaline PBMCs as a Model of Bacterial and Viral Infection. AB - In the present study, we used high-throughput sequencing, miRNA-seq, to discover and explore the expression profiles of known and novel miRNAs in TLR ligand stimulated vis-a-vis non-stimulated (i.e. Control) peripheral blood mononuclear cells (PBMCs) isolated from blood of healthy Murrah buffaloes. Six small RNA (sRNA) libraries were multiplexed in Ion Torrent PI chip and sequenced on Ion Proton System. The reads obtained were aligned to the Bos taurus genome (UMD3.1 assembly), which is phylogenetically closest species to buffalo (Bubalus bubalis). A total of 160 bovine miRNAs were biocomputationally identified in buffalo PBMCs and 130 putatively novel miRNAs (not enlisted in the bovine mirBase) were identified. All of these 290 miRNAs identified across the six treatment and control samples represent the repertoire of novel miRNAs for the buffalo species. The expression profiles of these miRNAs across the samples have been represented by sample dendrogram and heatmap plots. The uniquely expressed miRNAs in each treatment and control groups were identified. A few miRNAs were expressed at very high levels while the majority of them were moderately expressed. The miRNAs bta-miR-103 and -191 were found to be highly abundant and expressed in all the samples. Other abundantly expressed miRNAs include bta-miR 19b, -29b, -15a, -19a, -30d, -30b-5p and members of let family (let 7a-5p, let 7g & let 7f) in LPS and CpG treated PBMCS and bta-miR-191, -103 & -19b in Poly I:C stimulated PBMCs. Only one novel miRNA (bta-miR-11039) out of 130 identified putatively novel miRNAs, was expressed in all the six samples and differentially expressed (>2- fold) miRNAs were identified. Six of the differentially expressed miRNAs across the groups (bta-miR-421, bta-let-7i, bta-miR-138, bta-miR-21-5p, bta-miR-222 and bta-miR-27b) were subsequently confirmed by TaqMan quantitative reverse transcription polymerase chain reaction (qRT-PCR). Furthermore, the target genes of differentially expressed miRNAs were enriched for the roles in innate immunity and TLR signaling pathways. This maiden study on profiling and cataloguing of bubaline miRNAs expressed in TLR-ligand stimulated PBMCs will provide an important reference point for future studies on regulatory roles of miRNAs in immune system of buffaloes. PMID- 27257789 TI - New Pneumococcal Carriage Acquired in Association with Acute Respiratory Infection Is Prone to Cause Otitis Media. AB - For considering vaccine-prevention of pneumococcal acute otitis media (PncAOM), relationships between pneumococcal carriage, respiratory infection and PncAOM need to be understood. We analyzed nasopharyngeal samples collected from 329 unvaccinated Finnish children aged 2-24 months at scheduled visits and at visits during respiratory infection in 1994-97. We assessed temporal associations of respiratory infection with pneumococcal acquisition and whether PncAOM hazard depends on the relative timing of acquisition and the infection onset. The data comprised 607 person-years of risk-time for acquisition, 245 person-months of concurrent respiratory infection and carriage, and 119 episodes of PncAOM. The acquisition hazard was 3-fold in the month preceding respiratory sickness (hazard ratio, HR 3.5, 90% credible interval CI 2.9, 4.1) as compared to acquisition in healthy children. Moreover, the PncAOM hazard was markedly higher (HR 3.7, 90% CI 2.4, 5.3) during the first month of carriage acquired around the acute phase of respiratory infection (between 1 month before and 1 week after the sickness onset), as compared to carriage acquired later during sickness. The high proportion (76%) of PncAOM events occurring within 1 month of acquisition was due to frequent acquisition being associated with respiratory infection as well as the susceptibility of such acquisition to cause otitis media. PMID- 27257790 TI - Common Marker Genes Identified from Various Sample Types for Systemic Lupus Erythematosus. AB - OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex auto-immune disease. Gene expression studies have been conducted to identify SLE-related genes in various types of samples. It is unknown whether there are common marker genes significant for SLE but independent of sample types, which may have potentials for follow-up translational research. The aim of this study is to identify common marker genes across various sample types for SLE. METHODS: Based on four public microarray gene expression datasets for SLE covering three representative types of blood-born samples (monocyte; peripheral blood mononuclear cell, PBMC; whole blood), we utilized three statistics (fold-change, FC; t-test p value; false discovery rate adjusted p value) to scrutinize genes simultaneously regulated with SLE across various sample types. For common marker genes, we conducted the Gene Ontology enrichment analysis and Protein-Protein Interaction analysis to gain insights into their functions. RESULTS: We identified 10 common marker genes associated with SLE (IFI6, IFI27, IFI44L, OAS1, OAS2, EIF2AK2, PLSCR1, STAT1, RNASE2, and GSTO1). Significant up-regulation of IFI6, IFI27, and IFI44L with SLE was observed in all the studied sample types, though the FC was most striking in monocyte, compared with PBMC and whole blood (8.82-251.66 vs. 3.73-74.05 vs. 1.19 1.87). Eight of the above 10 genes, except RNASE2 and GSTO1, interact with each other and with known SLE susceptibility genes, participate in immune response, RNA and protein catabolism, and cell death. CONCLUSION: Our data suggest that there exist common marker genes across various sample types for SLE. The 10 common marker genes, identified herein, deserve follow-up studies to dissert their potentials as diagnostic or therapeutic markers to predict SLE or treatment response. PMID- 27257791 TI - Effects of Hypobaric Treatments on the Quality, Bioactive Compounds, and Antioxidant Activity of Tomato. AB - Hypobaric treatment is becoming a potential technology to protect fruits from postharvest decay. The objective of this study was to investigate the effects of hypobaric treatments on storage quality, bioactive compounds, and antioxidant activity of tomato fruit. In this study, green tomatoes (cv. "Fen guan") were treated with hypobaric pressures (0.04 and 0.07 MPa) at ambient temperature (20 C) for 28 d. The results showed that under hypobaric storage, the respiration rates significantly declined and the respiratory peaks postponed 12 and 8 d by 0.04 and 0.07 MPa treatments, respectively, compared to control. Total soluble solid, titratable acidity, ascorbic acid, and lycopene were retained by hypobaric treatment. Moreover, ascorbic acid contents treated with 0.04 and 0.07 MPa were, respectively, 37% and 26% higher than control at day 24 and the contents of total polyphenols were, respectively, 1.28 and 1.11 times higher than control. Production and accumulation of toxic substances were significantly restrained. The ethanol content decreased, respectively, by 53% and 84% than control. At later storage period, the superoxide dismutase activity in treated fruits was about 0.58 U/(g.FW.min), whereas only 0.29 U/(g.FW.min) in control. Hypobaric treatment not only maintained a high activity of superoxide dismutase and peroxidase (POD), but also improved antioxidant capacity. All the results indicated that hypobaric treatment was a potential helpful method to protect the quality and nutrition of tomato and prolong ripening of tomato. Furthermore, the effect of 0.04 MPa hypobaric treatment was found better than 0.07 MPa. PMID- 27257792 TI - Surface oxidation effect on the electrical behaviour of Bi2Te2Se nanoplatelets. AB - Charge transport in topological insulators is notably influenced by moisture and air in the surrounding environment. At present, however, little is known about the detailed composition of the oxidized surface and its impact on the electrical characteristics of these materials. Here, we investigate the surface oxide formation on the topological insulator Bi2Te2Se (BTS) and how this affects its electrical behavior. While ambient exposure of BTS nanoplatelets predominantly creates surface hydroxyl groups, oxygen plasma treatment yields a compact, few nanometer thick surface oxide layer. The plasma causes p-type doping, accompanied by a decrease of the effective platelet thickness, the interplay of which is manifested in a resistance maximum as a function of plasma treatment time. It is furthermore demonstrated that the structural integrity of the plasma-derived surface oxide is sufficient to enable its use as a gate insulator layer in combination with a top gate. PMID- 27257793 TI - Personal protective equipment and improving compliance among healthcare workers in high-risk settings. AB - PURPOSE OF REVIEW: Personal protective equipment (PPE) protects healthcare workers (HCWs) from infection by highly virulent pathogens via exposure to body fluids and respiratory droplets. Given the recent outbreaks of contagious infectious diseases worldwide, including Ebola virus and Middle Eastern respiratory syndrome, there is urgent need for further research to determine optimal PPE use in high-risk settings. This review intends to provide a general understanding of PPE and to provide guidelines for appropriate use based on current evidence. RECENT FINDINGS: Although previous studies have focused on the efficacy of PPE in preventing transmission of pathogens, recent studies have examined the dangers to HCWs during removal of PPE when risk of contamination is highest. Access to adequate PPE supplies is crucial to preventing transmission of pathogens, especially in resource-limited settings. Adherence to appropriate PPE use is a challenge due to inadequate education on its usage, technical difficulties, and tolerability of PPE in the workplace. Future projects aim at ameliorating this situation, including redesigning PPE which is crucial to improving the safety of HCWs. SUMMARY: PPE remains the most important strategy for protecting HCW from potentially fatal pathogens. Further research into optimal PPE design and use to improve the safety of HCWs is urgently needed. PMID- 27257794 TI - Electronic surveillance and using administrative data to identify healthcare associated infections. AB - PURPOSE OF REVIEW: Traditional surveillance of healthcare associated infections (HCAI) is time consuming and error-prone. We have analysed literature of the past year to look at new developments in this field. It is divided into three parts: new algorithms for electronic surveillance, the use of administrative data for surveillance of HCAI, and the definition of new endpoints of surveillance, in accordance with an automatic surveillance approach. RECENT FINDINGS: Most studies investigating electronic surveillance of HCAI have concentrated on bloodstream infection or surgical site infection. However, the lack of important parameters in hospital databases can lead to misleading results. The accuracy of administrative coding data was poor at identifying HCAI. New endpoints should be defined for automatic detection, with the most crucial step being to win clinicians' acceptance. SUMMARY: Electronic surveillance with conventional endpoints is a successful method when hospital information systems implemented key changes and enhancements. One requirement is the access to systems for hospital administration and clinical databases.Although the primary source of data for HCAI surveillance is not administrative coding data, these are important components of a hospital-wide programme of automated surveillance. The implementation of new endpoints for surveillance is an approach which needs to be discussed further. PMID- 27257795 TI - Strategies to prevent BK virus infection in kidney transplant recipients. AB - PURPOSE OF REVIEW: Despite improvements in posttransplant care, BK virus (BKV) remains one of the most challenging posttransplant infections in kidney transplant recipients with high rates of allograft failure. In the absence of well tolerated and efficacious viral specific therapeutics, treatment is primarily focused on reduction of immunosuppression, which poses a risk of rejection and fails to lead to viral clearance in a number of patients. RECENT FINDINGS: Recent work has turned toward preventive therapies analogous to those used for other infections like cytomegalovirus. These efforts have focused on the use of quinolone antibiotic prophylaxis to prevent BKV infection and pretransplant vaccination to boost humoral and cellular immunity. SUMMARY: Despite promising in-vitro and observational data, quinolone antibiotic prophylaxis has not been effective in preventing BKV infection in prospective studies. However, prophylaxis with newer less toxic viral specific agents such as brincidofovir - the lipid oral formulation of cidofovir - may yet prove effective. Strategies focused on eliciting a humoral immune response to recombinant virus-like particles or using adoptive transfer of BKV-specific T cells have also shown significant potential to prevent BKV infection in organ transplant recipients. PMID- 27257796 TI - Prevention of common healthcare-associated infections in humanitarian hospitals. AB - PURPOSE OF REVIEW: Humanitarian medical organizations focus on vulnerable patients with increased risk for healthcare-associated infections (HAIs) and are obligated to minimize them in inpatient departments (IPDs). However, in doing so humanitarian groups face considerable obstacles. This report will focus on approaches to reducing common HAIs that the authors have found to be helpful in humanitarian settings. RECENT FINDINGS: HAIs are common in humanitarian contexts but there are few interventions or guidelines adapted for use in poor and conflict-affected settings to improve prevention and guide surveillance. Based on existing recommendations and studies, it appears prudent that all humanitarian IPDs introduce a basic infection prevention infrastructure, assure high adherence to hand hygiene with wide accessibility to alcohol-based hand rub, and develop pragmatic surveillance based on clinically evident nosocomial infection. Although microbiology remains out of reach for most humanitarian hospitals, rapid tests offer the possibility of improving the diagnosis of HAIs in humanitarian hospitals in the decade ahead. SUMMARY: There is a dearth of new studies that can direct efforts to prevent HAIs in IPDs in poor and conflict-affected areas and there is a need for practical, field-adapted guidelines from professional societies, and international bodies to guide infection prevention efforts in humanitarian environments. PMID- 27257797 TI - Infections associated with the use of eculizumab: recommendations for prevention and prophylaxis. AB - PURPOSE OF REVIEW: Eculizumab inhibits complement effector functions and has significantly impacted the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. However, the risks of potentially life threatening infections, notably with Neisseria spp. in addition to its cost, are major challenges in clinical practice. In this review, we characterize and summarize the infectious complications reported with the use of eculizumab in the context of its typical and expanding indications. RECENT FINDINGS: Use of eculizumab is rapidly extending to the fields of transplantation and neurology. Eculizumab has been primarily associated with an increased risk of meningococcal infections. Immunization against its commonest serotypes (ABCWY) is now possible with the advent of the meningococcal B vaccine. A combined ABCWY vaccine is underway. Preventive strategies against breakthrough Neisseria infections should also include chemoprophylaxis. Less is known about the association of eculizumab with other infections as recently reported. Surrogate markers of complement blockade, notably CH50, and eculizumab efficacy may help in the risk assessment of infection. SUMMARY: Eculizumab has opened new horizons in the treatment of complement-mediated disorders. Prophylactic and immunization strategies against the risk of Nesseria spp. infections are sound and feasible. The use of eculizumab is expanding beyond complement-mediated diseases to transplantation and neurological disorders. Further research is needed to better define and stratify the risk of infection and prevention strategies in patients with the latter indications. PMID- 27257798 TI - 'No touch' technologies for environmental decontamination: focus on ultraviolet devices and hydrogen peroxide systems. AB - PURPOSE OF REVIEW: This article reviews 'no touch' methods for disinfection of the contaminated surface environment of hospitalized patients' rooms. The focus is on studies that assessed the effectiveness of ultraviolet (UV) light devices, hydrogen peroxide systems, and self-disinfecting surfaces to reduce healthcare associated infections (HAIs). RECENT FINDINGS: The contaminated surface environment in hospitals plays an important role in the transmission of several key nosocomial pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp., Clostridium difficile, Acinetobacter spp., and norovirus. Multiple clinical trials have now demonstrated the effectiveness of UV light devices and hydrogen peroxide systems to reduce HAIs. A limited number of studies have suggested that 'self-disinfecting' surfaces may also decrease HAIs. SUMMARY: Many studies have demonstrated that terminal cleaning and disinfection with germicides is often inadequate and leaves environmental surfaces contaminated with important nosocomial pathogens. 'No touch' methods of room decontamination (i.e., UV devices and hydrogen peroxide systems) have been demonstrated to reduce key nosocomial pathogens on inoculated test surfaces and on environmental surfaces in actual patient rooms. Further UV devices and hydrogen peroxide systems have been demonstrated to reduce HAI. A validated 'no touch' device or system should be used for terminal room disinfection following discharge of patients on contact precautions. The use of a 'self-disinfecting' surface to reduce HAI has not been convincingly demonstrated. PMID- 27257799 TI - Association of Football Subconcussive Head Impacts With Ocular Near Point of Convergence. AB - IMPORTANCE: An increased understanding of the relationship between subconcussive head impacts and near point of convergence (NPC) ocular-motor function may be useful in delineating traumatic brain injury. OBJECTIVE: To investigate whether repetitive subconcussive head impacts during preseason football practice cause changes in NPC. DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational study of 29 National Collegiate Athletic Association Division I football players included baseline and preseason practices (1 noncontact and 4 contact), and postseason follow-up and outcome measures were obtained for each time. An accelerometer-embedded mouthguard measured head impact kinematics. Based on the sum of head impacts from all 5 practices, players were categorized into lower (n = 7) or higher (n = 22) impact groups. EXPOSURES: Players participated in regular practices, and all head impacts greater than 10g from the 5 practices were recorded using the i1Biometerics Vector mouthguard (i1 Biometrics Inc). MAIN OUTCOMES AND MEASURES: Near point of convergence measures and symptom scores. RESULTS: A total of 1193 head impacts were recorded from 5 training camp practices in the 29 collegiate football players; 22 were categorized into the higher-impact group and 7 into the lower-impact group. There were significant differences in head impact kinematics between lower- and higher-impact groups (number of impacts, 6 vs 41 [lower impact minus higher impact = 35; 95% CI, 21 51; P < .001]; linear acceleration, 99g vs 1112g [lower impact minus higher impact= 1013; 95% CI, 621 - 1578; P < .001]; angular acceleration, 7589 radian/s2 vs 65 016 radian/s2 [lower impact minus higher impact= 57 427; 95% CI , 31 123-80 498; P < .001], respectively). The trajectory and cumulative burden of subconcussive impacts on NPC differed by group (F for group * linear trend1, 238 = 12.14, P < .001 and F for group * quadratic trend1, 238 = 12.97, P < .001). In the higher-impact group, there was a linear increase in NPC over time (B for linear trend, unstandardized coefficient [SE]: 0.76 [0.12], P < .001) that plateaued and resolved by postseason follow-up (B for quadratic trend [SE]: -0.06 [0.008], P < .001). In the lower-impact group, there was no change in NPC over time. Group differences were first observed after the first contact practice and remained until the final full-gear practice. No group differences were observed postseason follow-up. There were no differences in symptom scores between groups over time. CONCLUSIONS AND RELEVANCE: Although asymptomatic, these data suggest that repetitive subconcussive head impacts were associated with changes in NPC. The increase in NPC highlights the vulnerability and slow recovery of the ocular motor system following subconcussive head impacts. Changes in NPC may become a useful clinical tool in deciphering brain injury severity. PMID- 27257800 TI - Psychometric Properties of the Kessler 10 Scale in Chinese Parents of Children With Cancer. AB - BACKGROUND: The Kessler Psychological Distress Scale (K10) has been widely used in rating psychological distress in general and clinical populations. However, whether it can be used in parents of children with cancer is unknown. Still lacking is the evidence on its reliability and validity in culturally diverse groups. OBJECTIVE: The aim of this study was to translate the K10 into Mandarin Chinese and test its psychometric properties (especially the factor structure) of the Chinese version (C-K10) in parents of children with cancer. METHODS: By convenience sampling, 2 samples of parents of children with cancer (sample I, n = 206, and sample II, n = 103) were surveyed in Guangzhou, China. Sample I completed the C-K10, and the internal consistency reliability and exploratory factor analysis of the C-K10 were estimated. Sample II completed the C-K10, the State Subscale of State-Trait Anxiety Inventory, and the Zung Self-rating Depression Scale; confirmatory factor analysis and concurrent validity estimates were completed. RESULTS: The C-K10 demonstrated strong internal consistency reliability (Cronbach's alpha = .93). Both exploratory and confirmatory factor analyses supported a 2-factor structure (ie, anxiety and depression). The concurrent validity was moderate with Pearson correlations greater than 0.50 (P < .001). CONCLUSION: The C-K10 demonstrated very acceptable reliability and validity in screening psychological distress in Chinese parents of children with cancer. IMPLICATIONS FOR PRACTICE: This study provides evidence that the C-K10 is a valid tool that can be used in clinical settings to screen for psychological distress in Chinese parents of children with cancer. PMID- 27257802 TI - Formation Kinetics of Oil-Rich, Nonionic Microemulsions. AB - The formation kinetics of oil-rich, nonionic microemulsions were investigated along different mixing pathways using a fast stopped-flow device in combination with the new high-flux small-angle neutron spectrometer D33 (ILL, Grenoble, France). While the kinetics along most pathways were too fast to be resolved, two processes could be detected mixing brine and the binary cyclohexane/C10E5 solution. Here, too, the formation of large water-in-oil droplets was found to be faster than 20 ms and therewith faster than the accessible dead time. However, subsequently, both the disintegration of the large water-in-oil droplets (600 A) and the uptake of water by swollen micelles (50-60 A) could be resolved. Both processes occur on the time scale of a second. Strikingly, the total internal interface forms faster than 20 ms and does not change over time. PMID- 27257803 TI - Oxidative Allylic Esterification of Alkenes by Cooperative Selenium-Catalysis Using Air as the Sole Oxidant. AB - A new metal-free catalysis protocol for the oxidative coupling of nonactivated alkenes with simple carboxylic acids has been established. This method is predicated on the cooperative interaction of a diselane and a photoredox catalyst, which allows for the use of ambient air or pure O2 as the terminal oxidant. Under the title conditions, a range of both functionalized and nonfunctionalized alkenes can be readily converted into the corresponding allylic ester products with good yields (up to 89%) and excellent regioselectivity as well as good functional group tolerance. PMID- 27257801 TI - Pilot Study of Parent Psychophysiologic Outcomes in Pediatric Hematopoietic Stem Cell Transplantation. AB - BACKGROUND: Parents of children undergoing hematopoietic stem cell transplantation (HSCT) are at risk for psychological distress. This distress may result in aberrant immune, inflammatory, or endocrine effects. These physiologic outcomes have not been reported previously. MAIN OBJECTIVE: The aim of this study is to examine the feasibility of longitudinal testing of psychophysiological parameters of stress in parents of children undergoing HSCT. METHODS: This pilot study was conducted at a large children's hospital in the Midwest and included parents of children who received autologous or allogeneic HSCT. Time points included before the start of HSCT conditioning and day +30, +60, and +100. Outcome variables included parent-perceived stress, lymphocyte subsets, C reactive protein (CRP), proinflammatory cytokines, salivary cortisol, and salivary amylase. Effect sizes were calculated for each outcome. RESULTS: Twelve parent-child dyads were enrolled (10 mothers, 2 fathers). Missing data were minimal. Parent-perceived stress significantly increased from pre-HSCT through day +100, and parent CD3+ T-lymphocyte counts decreased from pre-HSCT through day +100. No significant effects were observed for salivary studies, CRP, or proinflammatory cytokines. Effect sizes ranged from 1.23 (perceived stress) to 0.07 (CRP). CONCLUSION: The results of this study suggest that it is feasible longitudinally measure parent psychophysiologic outcomes in the pediatric HSCT setting. In addition, parent-perceived stress increased linearly from start of conditioning through day +100, whereas parent T-lymphocyte counts decreased concurrently. IMPLICATIONS FOR PRACTICE: Routine psychological and physical health screening of parents of children undergoing HSCT is needed. Multidisciplinary psychosocial support services should be offered to parents at regular intervals during their child's HSCT. PMID- 27257804 TI - Epidemiological and Virological Characterizations of the 2014 Dengue Outbreak in Guangzhou, China. AB - Dengue used to be recognized as an imported and sporadic disease in China. Since June 2014, an unexpected large dengue outbreak has attacked Guangzhou, China, resulting in more than 40,000 cases. Among the 1,942 laboratory-confirmed hospitalized dengue cases, 121 were diagnosed as severe dengue according to the 2009 WHO guideline, and 2 patients finally died. Laboratory diagnosis and virus isolation demonstrated that the majority (96%) cases were caused by dengue virus serotype 1 (DENV-1), and the others by serotype 2 (DENV-2). 14 DENV strains were isolated from the sera of acute-phase dengue patients during this outbreak, and the complete envelope (E) gene of 12 DENV-1 strains and two DENV-2 strains were determined using RT-PCR assay. Phylogenetic analysis based on the E gene revealed the DENV-1 strains isolated during the outbreak belonged to genotype I and V, respectively. These isolates formed three clades. DENV-2 isolates were assigned to the same clade belonging to genotype cosmopolitan. These strains isolated in 2014 were closely related to the isolates obtained from the same province, Guangdong, in 2013. No amino acid mutations known to increase virulence were identified throughout the E protein of isolates in 2014. These results indicate that dengue is turning into endemic in Guangdong, China, and extensive seroepidemiological investigation and mosquito control measures are critically needed in the future. PMID- 27257806 TI - Fate mapping of Trps1 daughter cells during cardiac development using novel Trps1 Cre mice. AB - Tricho-rhino-phalangeal syndrome (TRPS) is a rare congenital disorder that is characterized by abnormal hair growth and skeletal deformities. These result in sparse hair, short stature, and early onset of joint problems. Recent reports have shown that a relatively high proportion of patients with TRPS exhibit a broad range of congenital heart defects. To determine the regulation of Trps1 transcription in vivo, we generated novel transgenic mice, which expressed Cre recombinase under the murine Trps1 proximal promoter sequence (Trps1-Cre). We crossed these mice with Cre reporter mice to identify Trps1 daughter cells. Labeled cells were observed in the appendicular joint tissue, dermal papilla of the hair follicles, cardiac valves, aortic sinus, atrial walls, and the interventricular septum. In situ analysis showed restricted Trps1 expression, which was observed in endocardial cushions of the outflow tract, and in leaflets of all mature cardiac valves. These results suggest that the Trps1 proximal promoter sequence contains some of the tissue-specific Trps1 regulatory region. Further, our findings partially explain why patients with TRPS show a broad range of congenital cardiac defects, although Trps1 expression is observed in a more restricted fashion. genesis 54:379-388, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27257805 TI - Disease-Specific as Well as Generic Quality of Life Is Widely Impacted in Autoimmune Hypothyroidism and Improves during the First Six Months of Levothyroxine Therapy. AB - BACKGROUND: Hypothyroidism is often diagnosed, and subsequently treated, due to health-related quality of life (HRQL) issues. However, HRQL following treatment has never previously been assessed in longitudinal descriptive studies using validated instruments. OBJECTIVE: To investigate disease-specific (ThyPRO) and generic (SF-36) HRQL, following levothyroxine therapy in patients with hypothyroidism due to autoimmune thyroiditis. METHODS: This prospective cohort study was set at endocrine outpatient clinics at two Danish university hospitals. Seventy-eight consecutive patients were enrolled and completed HRQL questionnaires before, six weeks, and six months after initiation of levothyroxine therapy. Normative ThyPRO (n = 739) and SF-36 (n = 6,638) data were available for comparison and changes in HRQL following treatment were estimated and quantified. RESULTS: Prior to treatment, all ThyPRO scales were significantly impacted (p<0.0001), compared to the general population sample. The same was observed for seven of eight SF-36 scales, the exception being Bodily Pain. Tiredness (ThyPRO) and Vitality (SF-36) were the most markedly impacted scales. After six weeks of treatment, nine of thirteen ThyPRO scales had significantly improved. ThyPRO improvements were consistent at six months, where five of eight SF-36 scales had also significantly improved, but deficits persisted for a subset of both ThyPRO and SF-36 scales. CONCLUSIONS: In this population of hypothyroid patients, HRQL was widely affected before treatment, with tiredness as the cardinal impairment according to both ThyPRO and SF-36. Many aspects of HRQL improved during the first six months of LT4 therapy, but full recovery was not obtained. Our results may help clinicians inform patients about expected clinical treatment effects. PMID- 27257807 TI - Population Structure and Evolution after Speciation of the Hokkaido Salamander (Hynobius retardatus). AB - The Hokkaido salamander (Hynobius retardatus) is endemic to Hokkaido Island, Japan, and shows intriguing flexible phenotypic plasticity and regional morphological diversity. However, to date, allozymes and partial mitochondria DNA sequences have provided only an outline of its demographic histories and the pattern of its genetic diversification. To understand the finer details of the population structure of this species and its evolution since speciation, we genotyped five regional populations by using 12 recently developed microsatellite polymorphic markers. We found a clear population structure with low gene flow among the five populations, but a close genetic relationship between the Teshio and Kitami populations. Our demographic analysis suggested that Teshio and Erimo had the largest effective population sizes among the five populations. These findings regarding the population structure and demography of H. retardatus improve our understanding of the faunal phylogeography on Hokkaido Island and also provide fundamental genetic information that will be useful for future studies. PMID- 27257808 TI - Cost of Pediatric Visceral Leishmaniasis Care in Morocco. AB - BACKGROUND: Visceral leishmaniasis (VL) is a neglected parasitic disease that is fatal if left untreated. VL is endemic in Morocco and other countries in North Africa were it mainly affects children from rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow aspirates and serological tests are used to diagnose VL. Glucantime is the first line of treatment. The objective of this study was to report the costs associated to standard clinical management of pediatric VL from the provider perspective in Morocco. As a secondary objective we described the current clinical practices and the epidemiological characteristics of pediatric VL patients. METHODS: From March to June 2014 we conducted a survey in eight hospitals treating pediatric VL patients in Morocco. A pro-forma was used to collect demographic, clinical and management data from medical records. We specifically collected data on VL diagnosis and treatment. We also estimated the days of hospitalization and the time to start VL treatment. Costs were estimated by multiplying the use of resources in terms of number of days in hospital, tests performed and drugs provided by the official prices. For patients receiving part of their treatment at Primary Health Centers (PHC) we estimated the cost of administering the Glucantime as outpatient. We calculated the median cost per VL patient. We also estimated the cost of managing a VL case when different treatment strategies were applied: inpatient and outpatient. RESULTS: We obtained data from 127 VL patients. The median total cost per pediatric VL case in Morocco is 520 US$. The cost in hospitals applying an outpatient strategy is significantly lower (307 US$) than hospitals keeping the patients for the whole treatment (636 US$). However the outpatient strategy is not yet recommended as VL treatment for children in the Moroccan guidelines. VL diagnosis and treatment regimens should be standardized following the current guidelines in Morocco. PMID- 27257809 TI - Understanding Vaccine Hesitancy in Canada: Results of a Consultation Study by the Canadian Immunization Research Network. AB - "Vaccine hesitancy" is a concept now frequently used in vaccination discourse. The increased popularity of this concept in both academic and public health circles is challenging previously held perspectives that individual vaccination attitudes and behaviours are a simple dichotomy of accept or reject. A consultation study was designed to assess the opinions of experts and health professionals concerning the definition, scope, and causes of vaccine hesitancy in Canada. We sent online surveys to two panels (1- vaccination experts and 2- front-line vaccine providers). Two questionnaires were completed by each panel, with data from the first questionnaire informing the development of questions for the second. Our participants defined vaccine hesitancy as an attitude (doubts, concerns) as well as a behaviour (refusing some / many vaccines, delaying vaccination). Our findings also indicate that both vaccine experts and front-line vaccine providers have the perception that vaccine rates have been declining and consider vaccine hesitancy an important issue to address in Canada. Diffusion of negative information online and lack of knowledge about vaccines were identified as the key causes of vaccine hesitancy by the participants. A common understanding of vaccine hesitancy among researchers, public health experts, policymakers and health care providers will better guide interventions that can more effectively address vaccine hesitancy within Canada. PMID- 27257810 TI - Effects of Land Cover on the Movement of Frugivorous Birds in a Heterogeneous Landscape. AB - Movement is a key spatiotemporal process that enables interactions between animals and other elements of nature. The understanding of animal trajectories and the mechanisms that influence them at the landscape level can yield insight into ecological processes and potential solutions to specific ecological problems. Based upon optimal foraging models and empirical evidence, we hypothesized that movement by thrushes is highly tortuous (low average movement speeds and homogeneous distribution of turning angles) inside forests, moderately tortuous in urban areas, which present intermediary levels of resources, and minimally tortuous (high movement speeds and turning angles next to 0 radians) in open matrix types (e.g., crops and pasture). We used data on the trajectories of two common thrush species (Turdus rufiventris and Turdus leucomelas) collected by radio telemetry in a fragmented region in Brazil. Using a maximum likelihood model selection approach we fit four probability distribution models to average speed data, considering short-tailed, long-tailed, and scale-free distributions (to represent different regimes of movement variation), and one distribution to relative angle data. Models included land cover type and distance from forest matrix edges as explanatory variables. Speed was greater farther away from forest edges and increased faster inside forest habitat compared to urban and open matrices. However, turning angle was not influenced by land cover. Thrushes presented a very tortuous trajectory, with many displacements followed by turns near 180 degrees. Thrush trajectories resembled habitat and edge dependent, tortuous random walks, with a well-defined movement scale inside each land cover type. Although thrushes are habitat generalists, they showed a greater preference for forest edges, and thus may be considered edge specialists. Our results reinforce the importance of studying animal movement patterns in order to understand ecological processes such as seed dispersal in fragmented areas, where the percentage of remaining habitat is dwindling. PMID- 27257811 TI - Correction: Tbx18 Regulates the Differentiation of Periductal Smooth Muscle Stroma and the Maintenance of Epithelial Integrity in the Prostate. AB - [This corrects the article DOI: 10.1371/journal.pone.0154413.]. PMID- 27257812 TI - The Role of Adaptation in Bacterial Speed Races. AB - Evolution of biological sensory systems is driven by the need for efficient responses to environmental stimuli. A paradigm among prokaryotes is the chemotaxis system, which allows bacteria to navigate gradients of chemoattractants by biasing their run-and-tumble motion. A notable feature of chemotaxis is adaptation: after the application of a step stimulus, the bacterial running time relaxes to its pre-stimulus level. The response to the amino acid aspartate is precisely adapted whilst the response to serine is not, in spite of the same pathway processing the signals preferentially sensed by the two receptors Tar and Tsr, respectively. While the chemotaxis pathway in E. coli is well characterized, the role of adaptation, its functional significance and the ecological conditions where chemotaxis is selected, are largely unknown. Here, we investigate the role of adaptation in the climbing of gradients by E. coli. We first present theoretical arguments that highlight the mechanisms that control the efficiency of the chemotactic up-gradient motion. We discuss then the limitations of linear response theory, which motivate our subsequent experimental investigation of E. coli speed races in gradients of aspartate, serine and combinations thereof. By using microfluidic techniques, we engineer controlled gradients and demonstrate that bacterial fronts progress faster in equal magnitude gradients of serine than aspartate. The effect is observed over an extended range of concentrations and is not due to differences in swimming velocities. We then show that adding a constant background of serine to gradients of aspartate breaks the adaptation to aspartate, which results in a sped-up progression of the fronts and directly illustrate the role of adaptation in chemotactic gradient-climbing. PMID- 27257813 TI - Conessine Interferes with Oxidative Stress-Induced C2C12 Myoblast Cell Death through Inhibition of Autophagic Flux. AB - Conessine, a steroidal alkaloid isolated from Holarrhena floribunda, has anti malarial activity and interacts with the histamine H3 receptor. However, the cellular effects of conessine are poorly understood. Accordingly, we evaluated the involvement of conessine in the regulation of autophagy. We searched natural compounds that modulate autophagy, and conessine was identified as an inhibitor of autophagic flux. Conessine treatment induced the formation of autophagosomes, and p62, an autophagic adapter, accumulated in the autophagosomes. Reactive oxygen species such as hydrogen peroxide (H2O2) result in muscle cell death by inducing excessive autophagic flux. Treatment with conessine inhibited H2O2 induced autophagic flux in C2C12 myoblast cells and also interfered with cell death. Our results indicate that conessine has the potential effect to inhibit muscle cell death by interfering with autophagic flux. PMID- 27257815 TI - Correction: Passive Leg Raising Correlates with Future Exercise Capacity after Coronary Revascularization. AB - [This corrects the article DOI: 10.1371/journal.pone.0137846.]. PMID- 27257814 TI - Morphological Computation of Haptic Perception of a Controllable Stiffness Probe. AB - When people are asked to palpate a novel soft object to discern its physical properties such as texture, elasticity, and even non-homogeneity, they not only regulate probing behaviors, but also the co-contraction level of antagonistic muscles to control the mechanical impedance of fingers. It is suspected that such behavior tries to enhance haptic perception by regulating the function of mechanoreceptors at different depths of the fingertips and proprioceptive sensors such as tendon and spindle sensors located in muscles. In this paper, we designed and fabricated a novel two-degree of freedom variable stiffness indentation probe to investigate whether the regulation of internal stiffness, indentation, and probe sweeping velocity (PSV) variables affect the accuracy of the depth estimation of stiff inclusions in an artificial silicon phantom using information gain metrics. Our experimental results provide new insights into not only the biological phenomena of haptic perception but also new opportunities to design and control soft robotic probes. PMID- 27257816 TI - Can Network Linkage Effects Determine Return? Evidence from Chinese Stock Market. AB - This study used the dynamic conditional correlations (DCC) method to identify the linkage effects of Chinese stock market, and further detected the influence of network linkage effects on magnitude of security returns across different industries. Applying two physics-derived techniques, the minimum spanning tree and the hierarchical tree, we analyzed the stock interdependence within the network of the China Securities Index (CSI) industry index basket. We observed that that obvious linkage effects existed among stock networks. CII and CCE, CAG and ITH as well as COU, CHA and REI were confirmed as the core nodes in the three different networks respectively. We also investigated the stability of linkage effects by estimating the mean correlations and mean distances, as well as the normalized tree length of these indices. In addition, using the GMM model approach, we found inter-node influence within the stock network had a pronounced effect on stock returns. Our results generally suggested that there appeared to be greater clustering effect among the indexes belonging to related industrial sectors than those of diverse sectors, and network comovement was significantly affected by impactive financial events in the reality. Besides, stocks that were more central within the network of stock market usually had higher returns for compensation because they endured greater exposure to correlation risk. PMID- 27257817 TI - Transcriptional Activity of rRNA Genes in Barley Cells after Mutagenic Treatment. AB - In the present study, the combination of the micronucleus test with analysis of the activity of the rRNA genes in mutagen-treated Hordeum vulgare (barley) by maleic hydrazide (MH) cells was performed. Simultaneously fluorescence in situ hybridization (FISH) with 25S rDNA as probes and an analysis of the transcriptional activity of 35S rRNA genes with silver staining were performed. The results showed that transcriptional activity is always maintained in the micronuclei although they are eliminated during the next cell cycle. The analysis of the transcriptional activity was extended to barley nuclei. MH influenced the fusion of the nucleoli in barley nuclei. The silver staining enabled detection of the nuclear bodies which arose after MH treatment. The results confirmed the usefulness of cytogenetic techniques in the characterization of micronuclei. Similar analyses can be now extended to other abiotic stresses to study the response of plant cells to the environment. PMID- 27257818 TI - The Effects of Adipose-Derived Stem Cells in a Rat Model of Tobacco-Associated Erectile Dysfunction. AB - Tobacco use is associated with erectile dysfunction (ED) via a number of mechanisms including vascular injury and oxidative stress in corporal tissue. Adipose derived stem cells (ADSC) have been shown to ameliorate vascular/corporal injury and oxidative stress by releasing cytokines, growth factors and antioxidants. We assessed the therapeutic effects of intracavernous injection of ADSC in a rat model of tobacco-associated ED. Thirty male rats were used in this study. Ten rats exposed to room air only served as negative controls. The remaining 20 rats were passively exposed to cigarette smoke (CS) for 12 weeks. At the 12-week time point, ADSC were isolated from paragonadal fat in all rats. Amongst the 20 CS exposed rats, 10 each were assigned to one of the two following conditions: (i) injection of phosphate buffered saline (PBS) into the corpora cavernosa (CS+PBS); or (ii) injection of autologous ADSC in PBS into the corpora cavernosa (CS+ADSC). Negative control animals received PBS injection into the corpora cavernosa (normal rats [NR] + PBS). After injections all rats were returned to their previous air versus CS exposure state. Twenty-eight days after injection, all rats were placed in a metabolic cage for 24-hour urine collection to be testing for markers of oxidative stress. After 24-hour urine collection all 30 rats also underwent erectile function testing via intracavernous pressure (ICP) testing and were then sacrificed. Corporal tissues were obtained for histological assessment and Western blotting. Mean body weight was significantly lower in CS-exposed rats than in control animals. Mean ICP, ICP /mean arterial pressure ratio, serum nitric oxide level were significantly lower in the CS+PBS group compared to the NR+PBS and CS+ADSC groups. Urine markers for oxidative stress were significantly higher in the CS+PBS group compared to the NR+PBS and CS+ADSC groups. Mean expression of corporal nNOS and histological markers for endothelial and smooth muscle cells was significantly lower, and tissue apoptotic index significantly higher, in the CS+PBS group compared to the NR+PBS and CS+ADSC groups. Our findings confirm that chronic tobacco exposure causes ultrastructural damage to the corporal tissue and increases systemic oxidative stress states. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential therapy for tobacco-related ED. PMID- 27257819 TI - A Phylogeographic Assessment of the Malagasy Giant Chameleons (Furcifer verrucosus and Furcifer oustaleti). AB - The Malagasy giant chameleons (Furcifer oustaleti and Furcifer verrucosus) are sister species that are both broadly distributed in Madagascar, and also endemic to the island. These species are also morphologically similar and, because of this, have been frequently misidentified in the field. Previous studies have suggested that cryptic species are nested within this chameleon group, and two subspecies have been described in F. verrucosus. In this study, we utilized a phylogeographic approach to assess genetic diversification within these chameleons. This was accomplished by (1) identifying clades within each species supported by both mitochondrial and nuclear DNA, (2) assessing divergence times between clades, and (3) testing for niche divergence or conservatism. We found that both F. oustaleti and F. verrucosus could be readily identified based on genetic data, and within each species, there are two well-supported clades. However, divergence times are not contemporary and spatial patterns are not congruent. Diversification within F. verrucosus occurred during the Plio Pleistocene, and there is evidence for niche divergence between a southwestern and southeastern clade, in a region of Madagascar that shows no obvious landscape barriers to dispersal. Diversification in F. oustaleti occurred earlier in the Pliocene or Miocene, and niche conservatism is supported with two genetically distinct clades separated at the Sofia River in northwestern Madagascar. Divergence within F. verrucosus is most consistent with patterns expected from ecologically mediated speciation, whereas divergence in F. oustaleti most strongly matches the patterns expected from the riverine barrier hypothesis. PMID- 27257820 TI - Identification of arsenic resistant endophytic bacteria from Pteris vittata roots and characterization for arsenic remediation application. AB - Mitigation of arsenic (As) pollution is a topical environmental issue of high R&D priority. The present investigation was carried out to isolate As resistant endophytes from the roots of Indian ecotype Pteris vittata and characterize their As transformation and tolerance ability, plant growth promoting characteristics and their role to facilitate As uptake by the plant. A total of 8 root endophytes were isolated from plants grown in As amended soil (25 mg As kg(-1)). These isolates were studied for minimum inhibitory concentration (MIC), arsenite As(III) - arsenate As(V) transformation ability, plant growth promoting (PGP) characteristics through siderophore, indole acetic acid (IAA) production, phosphatase, ACC deaminase activity, and presence of arsenite oxidase (aox) and arsenite transporter (arsB) genes. On the basis of 16S rDNA sequence analysis, these isolates belong to Proteobacteria, Firmicutes and Bacteroidetes families under the genera Bacillus, Enterobacter, Stenotrophomonas and Rhizobium. All isolates were found As tolerant, of which one isolates showed highest tolerance up to 1000 mg L(-1) concentration in SLP medium. Five isolates were IAA positive with highest IAA production up to 60 mg/L and two isolates exhibited siderophore activity. Phosphatase activity was shown by only one isolate while ACC deaminase activity was absent in all the isolates. The As transformation study by silver nitrate test showed that only two strains had dual characteristics of As(III) oxidation and As (V) reduction, four strains exhibited either of the characteristics while other two didn't confirmed any of the two characteristics. Presence of aox gene was detected in two strains and arsB gene in six isolates. The strain with highest As tolerance also showed highest IAA production and occurrence of arsB gene. Present investigation may open up further scope of utilizing these endophytes for up gradation of phytoextraction process. PMID- 27257821 TI - Identification of White Wines by using Two Oppositely Charged Poly(p phenyleneethynylene)s Individually and in Complex. AB - We present a simple array composed of an anionic and a cationic poly(para phenyleneethynylene) (PPE), together with an electrostatic complex between the two of them. The individual PPEs and the PPE complex were employed in the sensing of white wines at pH 13; the complex was also successfully employed as a sensor element at pH 3. The sensing mechanism is fluorescence quenching. Thirteen different wines were differentiated by this chemical tongue, which consists of four elements. The fluorescence quenching is not induced by the major components of the wines. Compounds such as acids, sugars, and alcohols alone do not quench the fluorescence, but rather the colored tannins and other polyphenols contained in wine are the main quenchers. However, the major constituents of wine significantly modulate the quenching of the PPEs by the tannins. PMID- 27257822 TI - Comparative Epidemiologic Characteristics of Pertussis in 10 Central and Eastern European Countries, 2000-2013. AB - We undertook an epidemiological survey of the annual incidence of pertussis reported from 2000 to 2013 in ten Central and Eastern European countries to ascertain whether increased pertussis reports in some countries share common underlying drivers or whether there are specific features in each country. The annual incidence of pertussis in the participating countries was obtained from relevant government institutions and/or national surveillance systems. We reviewed the changes in the pertussis incidence rates in each country to explore differences and/or similarities between countries in relation to pertussis surveillance; case definitions for detection and confirmation of pertussis; incidence and number of cases of pertussis by year, overall and by age group; population by year, overall and by age group; pertussis immunization schedule and coverage, and switch from whole-cell pertussis vaccines (wP) to acellular pertussis vaccines (aP). There was heterogeneity in the reported annual incidence rates and trends observed across countries. Reported pertussis incidence rates varied considerably, ranging from 0.01 to 96 per 100,000 population, with the highest rates generally reported in Estonia and the lowest in Hungary and Serbia. The greatest burden appears for the most part in infants (<1 year) in Bulgaria, Hungary, Latvia, Romania, and Serbia, but not in the other participating countries where the burden may have shifted to older children, though surveillance of adults may be inappropriate. There was no consistent pattern associated with the switch from wP to aP vaccines on reported pertussis incidence rates. The heterogeneity in reported data may be related to a number of factors including surveillance system characteristics or capabilities, different case definitions, type of pertussis confirmation tests used, public awareness of the disease, as well as real differences in the magnitude of the disease, or a combination of these factors. Our study highlights the need to standardize pertussis detection and confirmation in surveillance programs across Europe, complemented with carefully-designed seroprevalence studies using the same protocols and methodologies. PMID- 27257823 TI - Frailty as a Predictor of Acute Kidney Injury in Hospitalized Elderly Patients: A Single Center, Retrospective Cohort Study. AB - BACKGROUND: Elderly patients have an increased risk for acute kidney injury (AKI). However, few studies have reported on predictors for AKI in geriatric patients. Therefore, we aimed at determining the effect of frailty as a predictor of AKI. METHODS: We retrospectively enrolled 533 hospitalized elderly patients (aged >= 65 years) who had their creatinine levels measured (>= 1 measurement) during admission for a period of 1 year (2013) and conducted a comprehensive geriatric assessment (CGA) within 1 year before the index hospitalization. We examined five variables (activity of daily living [ADL] and instrumental ADL dependence, dementia, nutrition, and polypharmacy) from CGA. We categorized the patients into 3 groups according to the tertile of aggregate frailty scores: Group 1, score 1-2; Group 2, score 3-4; Group 3, score 5-8). RESULTS: Fifty-four patients (10.1%) developed AKI (median duration, 4 days). The frailest group (Group 3) showed an increased risk of AKI as compared to Group 1, (hazard ratio [HR] = 3.536, P = 0.002). We found that discriminatory accuracy for AKI improved with the addition of the tertile of aggregate frailty score to covariates (area under the receiver operator characteristics curves [AUROC] 0.641, AUROC 0.739, P = 0.004). Forty-six patients (8.6%) were transferred to nursing facilities and 477 patients (89.5%) were discharged home. The overall 90-day and 1-year mortality for elderly inpatients were 7.9% and 26.3%. The frailest group also demonstrated an increased risk of discharge to nursing facilities, and 90-day and 1-year mortality as compared to Group 1, independent of AKI severity (nursing facilities: odd ratio = 4.843, P = 0.002; 90-day mortality: HR = 6.555, P = 0.002; 1-year mortality: HR = 3.249, P = 0.001). CONCLUSIONS: We found that frailty may independently predict the development of AKI and adverse outcomes in geriatric inpatients. PMID- 27257825 TI - Comparison of the Surgical Outcomes of Dorsal Augmentation Using Expanded Polytetrafluoroethylene or Autologous Costal Cartilage. AB - IMPORTANCE: Dorsal augmentation material includes alloplastic implants and autologous tissues. However, there has been no comparison to date of dorsal augmentation using different materials performed by the same surgeon. OBJECTIVE: To compare the aesthetic outcomes and complications of dorsal augmentation using expanded polytetrafluoroethylene (ePTFE) and autologous costal cartilage (ACC) in rhinoplasty. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of the medical records of 244 patients who underwent dorsal augmentation performed by the same surgeon at the Asan Medical Center using ePTFE or ACC from March 1, 2003, through September 31, 2015. MAIN OUTCOMES AND MEASURES: Patient demographics and surgical procedures were analyzed. The aesthetic outcomes were scored from 1 (worst) to 4 (best) by 3 otolaryngologists. Changes in dorsal height and radix height were measured by comparing preoperative and postoperative profile views. Postoperative complications were also evaluated. RESULTS: A total of 244 patients who underwent augmentation rhinoplasty were reviewed in this study, including 141 men (57.8%) and 103 women (42.2%). The ePTFE group included 176 patients, and the ACC group comprised 68 patients. In the ePTFE and ACC groups, 96 patients (54.5%) and 45 patients (66.2%) were male, respectively. The patient ages ranged from 11 to 69 years, with a mean (SD) age of 30.3 (11.49) years in the ePTFE group and 36.04 (12.65) years in the ACC group. The mean (SD) aesthetic outcome scores were comparable between the 2 groups: 2.99 (0.05) in the ePTFE group and 2.99 (0.06) in the ACC group (P = .93). The change of dorsal (2.64% in ePTFE group and 5.82% in ACC group) and radix (3.62% in ePTFE group and 3.77% in ACC group) heights were significantly increased after augmentation in both groups (P < .001) even though the dorsal height of the ACC group after augmentation showed a significantly greater increase compared to the ePTFE group (P < .001). However, the complication rate was significantly higher in the ACC group: 4.0% in ePTFE group and 11.8% in ACC group (P = .02). CONCLUSIONS AND RELEVANCE: Dorsal augmentation with ACC produces similar aesthetic outcomes but a higher complication rate than dorsal augmentation with ePTFE. This higher complication rate may justify the use of ePTFE implants for dorsal augmentation in Asian patients undergoing rhinoplasty. LEVEL OF EVIDENCE: 3. PMID- 27257824 TI - Modeling the Dynamics of High-Grade Serous Ovarian Cancer Progression for Transvaginal Ultrasound-Based Screening and Early Detection. AB - High-grade serous ovarian cancer (HGSOC) represents the majority of ovarian cancers and accounts for the largest proportion of deaths from the disease. A timely detection of low volume HGSOC should be the goal of any screening studies. However, numerous transvaginal ultrasound (TVU) detection-based population studies aimed at detecting low-volume disease have not yielded reduced mortality rates. A quantitative invalidation of TVU as an effective HGSOC screening strategy is a necessary next step. Herein, we propose a mathematical model for a quantitative explanation on the reported failure of TVU-based screening to improve HGSOC low-volume detectability and overall survival.We develop a novel in silico mathematical assessment of the efficacy of a unimodal TVU monitoring regimen as a strategy aimed at detecting low-volume HGSOC in cancer-positive cases, defined as cases for which the inception of the first malignant cell has already occurred. Our findings show that the median window of opportunity interval length for TVU monitoring and HGSOC detection is approximately 1.76 years. This does not translate into reduced mortality levels or improved detection accuracy in an in silico cohort across multiple TVU monitoring frequencies or detection sensitivities. We demonstrate that even a semiannual, unimodal TVU monitoring protocol is expected to miss detectable HGSOC. Lastly, we find that circa 50% of the simulated HGSOC growth curves never reach the baseline detectability threshold, and that on average, 5-7 infrequent, rate-limiting stochastic changes in the growth parameters are associated with reaching HGSOC detectability and mortality thresholds respectively. Focusing on a malignancy poorly studied in the mathematical oncology community, our model captures the dynamic, temporal evolution of HGSOC progression. Our mathematical model is consistent with recent case reports and prospective TVU screening population studies, and provides support to the empirical recommendation against frequent HGSOC screening. PMID- 27257826 TI - Assessment of estrogenic and androgenic activity in PM10 air samples from an urban, industrial and rural area in Flanders (Belgium) using the CALUX bioassay. AB - BACKGROUND: Endocrine disrupting chemicals represent a broad class of compounds, are widespread in the environment and can pose severe health effects. OBJECTIVES: The objective of this study was to investigate and compare the overall estrogen and androgen activating potential of PM10 air samples at an urban, rural and industrial location in Flanders, using a human in vitro cell bioassay. METHODS: PM10 samples were collected on glass fiber filters every six days between April 2013 and January 2014 using a high-volume sampler. Extraction was executed with a hexane/acetone mixture before analysis using a recombinant estrogen- or androgen responsive human carcinoma cell line. Results were expressed as bioanalytical equivalents (BEQs) per cubic meter of air. RESULTS: High fluctuations in estrogenic activity were observed during the entire sampling period, with median BEQs of 32.1, 35.9 and 31.1 fg E2-Eq m(-)3 in the industrial, urban and rural background area, respectively. Estrogenic activity was measured in 70% of the samples, while no androgenic activity was observed in any of the samples. The estrogenic activity in the industrial area was positively correlated with the airborne concentration of the sum of the non-carcinogenic PAHs pyrene and fluoranthene (rho=0.48; p<0.01) and the sum of the carcinogenic PAHs (rho=0.36; p=0.05). CONCLUSIONS: This study showed that no androgenic activity was present in PM10 and that although the median estrogenic activity was rather low and comparable in the three locations, high fluctuations in estrogenic response exist over time. While atmospheric PAHs contributed to the observed estrogenic response, especially in the industrial area, the chemicals responsible for the majority of estrogenic activity remain to be identified. PMID- 27257828 TI - Synthesis of Tetracyclic Quinazolinones Using a Visible-Light-Promoted Radical Cascade Approach. AB - A practical approach for the synthesis of tetracyclic pyrroloquinazolines using photoredox strategy has been developed. The visible-light-promoted intramolecular single-electron-transfer process between photocatalyst and N-(2-iodobenzyl)-N acylcyanamides is considered to be involved in this transformation. Targeted pyrroloquinazoline derivatives (15 examples) are presented in good isolated yields (30%-88%). PMID- 27257827 TI - Interactions of cationic polystyrene nanoparticles with marine bivalve hemocytes in a physiological environment: Role of soluble hemolymph proteins. AB - The bivalve Mytilus galloprovincialis has proven as a suitable model invertebrate for evaluating the potential impact of nanoparticles (NPs) in the marine environment. In particular, in mussels, the immune system represents a sensitive target for different types of NPs. In environmental conditions, both NP intrinsic properties and those of the receiving medium will affect particle behavior and consequent bioavailability/uptake/toxicity. However, the evaluation of the biological effects of NPs requires additional understanding of how, once within the organism, NPs interact at the molecular level with cells in a physiological environment. In mammalian systems, different NPs associate with serum soluble components, organized into a "protein corona", which affects particle interactions with target cells. However, no information is available so far on the interactions of NPs with biological fluids of aquatic organisms. In this work, the influence of hemolymph serum (HS) on the in vitro effects of amino modified polystyrene NPs (PS-NH2) on Mytilus hemocytes was investigated. Hemocytes were incubated with PS-NH2 suspensions in HS (1, 5 and 50ug/mL) and the results were compared with those obtained in ASW medium. Cell functional parameters (lysosomal membrane stability, oxyradical production, phagocytosis) were evaluated, and morphological changes were investigated by TEM. The activation state of the signalling components involved in Mytilus immune response (p38 MAPK and PKC) was determined. The results show that in the presence of HS, PS-NH2 increased cellular damage and ROS production with respect to ASW medium. The effects were apparently mediated by disregulation of p38 MAPK signalling. The formation of a PS-NH2-protein corona in HS was investigated by centrifugation, and 1D- gel electrophoresis and nano-HPLC-ESI-MS/MS. The results identified the Putative C1q domain containing protein (MgC1q6) as the only component of the PS NH2 hard protein corona in Mytilus hemolymph. These data represent the first evidence for the formation of a NP bio-corona in aquatic organisms and underline the importance of the recognizable biological identity of NPs in physiological exposure medium when testing their potential impact environmental model organisms. Although the results obtained in vitro do not entirely reflect a realistic exposure scenario and the more complex formation of a bio-corona that is likely to occur in vivo, these data will contribute to a better understanding of the effects of NPs in marine invertebrates. PMID- 27257829 TI - Impact of subclinical coronary artery disease on the clinical outcomes of carotid endarterectomy. AB - OBJECTIVE Controversy persists regarding the optimal management of subclinical coronary artery disease (CAD) prior to carotid endarterectomy (CEA) and the impact of CAD on clinical outcomes after CEA. This study aimed to evaluate the short-term surgical risks and long-term outcomes of patients with subclinical CAD who underwent CEA. METHODS The authors performed a retrospective study of data from a prospective CEA registry. They analyzed a total of 702 cases involving patients without a history of CAD who received preoperative cardiac risk assessment by radionuclide myocardial perfusion imaging (MPI) and underwent CEA over a 10-year period. The management strategy (the necessity, sequence, and treatment modality of coronary revascularization and optimal perioperative medical treatment) was determined according to the presence, severity, and extent of CAD as determined by preoperative MPI and additional coronary computed tomography angiography and/or coronary angiography. Perioperative cardiac damage was defined on the basis of postoperative elevation of the blood level of cardiac troponin I (0.05-0.5 ng/ml) in the absence of myocardial ischemia. The primary endpoint was the composite of any stroke, myocardial infarction, or death during the perioperative period and all-cause mortality within 4 years of CEA. The associations between clinical outcomes after CEA and subclinical CAD were analyzed. RESULTS Concomitant subclinical CAD was observed in 81 patients (11.5%). These patients did have a higher incidence of perioperative cardiac damage (13.6% vs 0.5%, p < 0.01), but they had similar primary endpoint incidences during the perioperative period (2.5% vs.1.8%, p = 0.65) and similar estimated 4-year primary endpoint rates (13.6% vs 12.4%, p = 0.76) as the patients without subclinical CAD. Kaplan-Meier survival analysis showed that the 2 groups had similar rates of overall survival (p = 0.75). CONCLUSIONS Patients with subclinical CAD can undergo CEA with acceptable short- and long-term outcomes provided they receive selective coronary revascularization and optimal perioperative medical treatment. PMID- 27257830 TI - A leap forward in the endovascular management of acute basilar artery occlusion since the appearance of stent retrievers: a single-center comparative study. AB - OBJECTIVE Contrary to acute ischemic stroke involving the anterior circulation, no randomized trial has yet demonstrated the safety and effectiveness of endovascular management in acute basilar artery occlusion (BAO). Recently developed thrombectomy devices, such as stentrievers and aspiration systems, have helped in improving the endovascular management of acute ischemic stroke. The authors sought to assess the impact of these devices in the endovascular treatment of acute BAO. METHODS A retrospective analysis of 34 consecutive patients treated in Pitie-Salpetriere Hospital for acute BAO was carried out. All patients had undergone an endovascular procedure. In addition to the global results in terms of safety and effectiveness (recanalization rate and 3-month clinical outcome based on the modified Rankin Scale [mRS]), the authors aimed to determine if the patients treated with the most recently developed devices (i.e., the Solitaire stentriever or the ADAPT catheter) had better angiographic and clinical outcomes than those treated with older endovascular strategies. RESULTS The overall successful recanalization rate (thrombolysis in cerebral infarction score 2b-3) was 50% (17 of 34 patients). A good clinical outcome (mRS score 0-2 at 3-month follow-up) was achieved in 11 (32.3%) of 34 patients. The mortality rate at 3-month follow-up was 29.4% (10 of 34 patients). Patients treated with the Solitaire stentriever and the ADAPT catheter had a higher recanalization rate (12 [92.3%] of 13 patients vs 5 [23.8%] of 21 patients, p = 0.0002) and a shorter mean (+/- SD) procedure duration (88 +/- 31 minutes vs 126 +/- 58 minutes, p = 0.04) than patients treated with older devices. CONCLUSIONS The latest devices have improved the effectiveness of mechanical thrombectomy in acute BAO. Their use in further studies may help demonstrate a benefit in the endovascular management of acute BAO. PMID- 27257831 TI - High-grade glioma with anterior skull base erosion and intranasal extension: case report. AB - The authors describe the case of a large WHO Grade III anaplastic oligoastrocytoma extending through the anterior skull base and into the right nasal cavity and sinuses. Glial neoplasms are typically confined to the intracranial compartment within the brain parenchyma and rarely extend into the nasal cavity without prior surgical or radiation therapy. This 42-year-old woman presented with progressive headaches and sinus congestion. MR imaging findings revealed a large intracranial lesion with intranasal extension. Endoscopic nasal biopsy revealed pathology consistent with an infiltrating glioma. The patient subsequently underwent a combined transcranial/endonasal endoscopic approach for resection of this lesion. Pathological diagnosis revealed a WHO Grade III oligoastrocytoma. This report reviews the mechanisms of extradural glioma extension. To the authors' knowledge, it is the second report of a high-grade glioma exhibiting nasal extension without prior surgical or radiation treatment. PMID- 27257832 TI - The white matter tracts of the cerebrum in ventricular surgery and hydrocephalus. AB - OBJECTIVE The relationship of the white matter tracts to the lateral ventricles is important when planning surgical approaches to the ventricles and in understanding the symptoms of hydrocephalus. The authors' aim was to explore the relationship of the white matter tracts of the cerebrum to the lateral ventricles using fiber dissection technique and MR tractography and to discuss these findings in relation to approaches to ventricular lesions. METHODS Forty adult human formalin-fixed cadaveric hemispheres (20 brains) and 3 whole heads were examined using fiber dissection technique. The dissections were performed from lateral to medial, medial to lateral, superior to inferior, and inferior to superior. MR tractography showing the lateral ventricles aided in the understanding of the 3D relationships of the white matter tracts with the lateral ventricles. RESULTS The relationship between the lateral ventricles and the superior longitudinal I, II, and III, arcuate, vertical occipital, middle longitudinal, inferior longitudinal, inferior frontooccipital, uncinate, sledge runner, and lingular amygdaloidal fasciculi; and the anterior commissure fibers, optic radiations, internal capsule, corona radiata, thalamic radiations, cingulum, corpus callosum, fornix, caudate nucleus, thalamus, stria terminalis, and stria medullaris thalami were defined anatomically and radiologically. These fibers and structures have a consistent relationship to the lateral ventricles. CONCLUSIONS Knowledge of the relationship of the white matter tracts of the cerebrum to the lateral ventricles should aid in planning more accurate surgery for lesions within the lateral ventricles. PMID- 27257833 TI - Accessibility, reliability, and usability of neurosurgical resources. AB - OBJECTIVE Closing the knowledge gap that exists between patients and health care providers is essential and is facilitated by easy access to patient education materials. Although such information has the potential to be an effective resource, it must be written in a user-friendly and understandable manner, especially when such material pertains to specialized and highly technical fields such as neurological surgery. The authors evaluated the accessibility, usability, and reliability of current educational resources provided by the American Association of Neurological Surgeons (AANS), Healthwise, and the National Institute for Neurological Disorders and Stroke (NINDS). METHODS Online neurosurgical patient education information provided by AANS, Healthwise, and NINDS was evaluated using the LIDA scale, a website quality assessment tool, by medical professionals and nonmedical professionals. A high achieving score is regarded as 90% or greater using the LIDA scale. RESULTS Accessibility scores were 76.7% (AANS), 83.3% (Healthwise), and 75.0% (NINDS). Average usability scores for the AANS, Healthwise, and NINDS were 73.3%, 82.6%, and 82.9%, respectively, when evaluated by medical professionals and 78.5%, 80.7%, and 75.9%, respectively, for nonmedical professionals, respectively. Average reliability scores were 58.5%, 53.3%, 72.6%, respectively, for medical professionals and 70.4%, 66.7%, and 78.5%, respectively, for nonmedical professionals when evaluating the AANS, Healthwise, and NINDS websites. CONCLUSIONS Although organizations like AANS, Healthwise, and NINDS should be commended for their ongoing commitment to provide health care-oriented materials, modification of this material is suggested to improve the patient education value. PMID- 27257834 TI - Risk stratification in motor area-related glioma surgery based on navigated transcranial magnetic stimulation data. AB - OBJECTIVE Navigated transcranial magnetic stimulation (nTMS) is a noninvasive method for preoperatively localizing functional areas in patients with tumors in presumed motor eloquent areas. The aim of this study was to establish an nTMS based risk stratification model by examining whether the results of nTMS mapping and its neurophysiological data predict postoperative motor outcome in glioma surgery. METHODS Included in this study were prospectively collected data for 113 patients undergoing bihemispheric nTMS examination prior to surgery for gliomas in presumed motor eloquent locations. Multiple ordinal logistic regression analysis was performed to test for any association between preoperative nTMS related variables and postoperative motor outcome. RESULTS A new motor deficit or deterioration due to a preexisting deficit was observed in 20% of cases after 7 days and in 22% after 3 months. In terms of tumor location, no new permanent deficit was observed when the distance between tumor and corticospinal tract was greater than 8 mm and the precentral gyrus was not infiltrated (p = 0.014). New postoperative deficits on Day 7 were associated with a pathological excitability of the motor cortices (interhemispheric resting motor threshold [RMT] ratio < 90% or > 110%, p = 0.031). Interestingly, motor function never improved when the RMT was significantly higher in the tumorous hemisphere than in the healthy hemisphere (RMT ratio > 110%). CONCLUSIONS The proposed risk stratification model, based on objective functional-anatomical and neurophysiological measures, enables one to counsel patients about the risk of functional deterioration or the potential for recovery. PMID- 27257835 TI - Cesium-131 brachytherapy for recurrent brain metastases: durable salvage treatment for previously irradiated metastatic disease. AB - OBJECTIVE Managing patients whose intraparenchymal brain metastases recur after radiotherapy remains a challenge. Intraoperative cesium-131 (Cs-131) brachytherapy performed at the time of neurosurgical resection may represent an excellent salvage treatment option. The authors evaluated the outcomes of this novel treatment with permanent intraoperative Cs-131 brachytherapy. METHODS Thirteen patients with 15 metastases to the brain that recurred after stereotactic radiosurgery and/or whole brain radiotherapy were treated between 2010 and 2015. Stranded Cs-131 seeds were placed as a permanent volume implant. Prescription dose was 80 Gy at 5-mm depth from the resection cavity surface. The primary end point was resection cavity freedom from progression (FFP). Resection cavity freedom from progression (FFP), regional FFP, distant FFP, median survival, overall survival (OS), and toxicity were assessed. RESULTS The median duration of follow-up after salvage treatment was 5 months (range 0.5-18 months). The patients' median age was 64 years (range 51-74 years). The median resected tumor diameter was 2.9 cm (range 1.0-5.6 cm). The median number of seeds implanted was 19 (range 10-40), with a median activity per seed of 2.25 U (range 1.98-3.01 U) and median total activity of 39.6 U (range 20.0-95.2 U). The 1-year actuarial local FFP was 83.3%. The median OS was 7 months, and 1-year OS was 24.7%. Complications included infection (3), pseudomeningocele (1), seizure (1), and asymptomatic radionecrosis (RN) (1). CONCLUSIONS After failure of prior irradiation of brain metastases, re-irradiation with intraoperative Cs-131 brachytherapy implants provides durable local control and limits the risk of RN. The authors' initial experience demonstrates that this treatment approach is well tolerated and safe for patients with previously irradiated tumors after failure of more than 1 radiotherapy regimen and that it results in excellent response rates and minimal toxicity. PMID- 27257836 TI - Efficacy of a coaxial system with a compliant balloon catheter for navigation of the Penumbra reperfusion catheter in tortuous arteries: technique and case experience. AB - OBJECTIVE The authors describe a method by which they easily and atraumatically navigate a large-bore reperfusion catheter of the Penumbra system to an embolus by using a coaxial system with a compliant balloon catheter in patients with tortuous arteries. METHODS A retrospective review of the prospective endovascular database was performed to identify cases in which a coaxial system with a compliant balloon catheter (Scepter C, MicroVention/Terumo; or TransForm C, Stryker Neurovascular) and a large-bore reperfusion catheter of the Penumbra system (Penumbra, Inc.) was used. The authors achieved a stable guiding sheath position and delivered the coaxial system with a compliant balloon catheter and a large-bore reperfusion catheter. Then, the balloon was inflated somewhat when the distal tip of the balloon was slightly advanced from the tip of the reperfusion catheter, and together the coaxial system was advanced to an embolus over a 0.014 in guidewire, even around the corner. When the distal tip of the balloon catheter reached the embolus, the authors deflated the balloon and navigated the large bore reperfusion catheter to the embolus. Finally, the aspiration of the embolus with the Penumbra MAX pump was begun. RESULTS Between May 2014 and September 2015, the authors used this technique in 17 cases: 16 cases of middle cerebral artery occlusion (including 5 cases of internal carotid artery occlusion) and 1 case of basilar artery occlusion (age range 36-88 years, mean age 74.7 years, 13 men). For the reperfusion catheter of the Penumbra system, the 5MAX ACE was used in 15 cases, and the 5MAX was used in 2 cases. As a compliant balloon catheter, the Scepter C was used in 16 cases, and the TransForm C was used in 1 case. The technique was successful in 16 cases (94.1%). No parent artery dissections were noted in any cases. Catheter-induced vasospasm was noted in 1 case, but the vasospasm was transient. CONCLUSIONS A coaxial system with a compliant balloon catheter can help safely and easily to navigate the large-bore reperfusion catheter of the Penumbra system to an embolus in patients with tortuous arteries. PMID- 27257837 TI - Stagnation and complex flow in ruptured cerebral aneurysms: a possible association with hemostatic pattern. AB - OBJECT Histopathological examination has revealed that ruptured cerebral aneurysms have different hemostatic patterns depending on the location of the clot formation. In this study, the authors investigated whether the hemostatic patterns had specific hemodynamic features using computational fluid dynamics (CFD) analysis. METHODS Twenty-six ruptured middle cerebral artery aneurysms were evaluated by 3D CT angiography and harvested at the time of clipping. The hemostatic patterns at the rupture points were assessed by means of histopathological examination, and morphological parameters were obtained. Transient analysis was performed, and wall shear stress-related hemodynamic parameters and invariant Q (vortex core region) were calculated. The morphological and hemodynamic parameters were compared among the hemostatic patterns. RESULTS Hematoxylin and eosin staining of the aneurysm wall showed 13 inside-pattern, 9 outside-pattern, and 4 other-pattern aneurysms. Three of the 26 aneurysms were excluded from further analysis, because their geometry models could not be generated due to low vascular CT values. Mann-Whitney U-tests showed that lower dome volume (0.04 cm3 vs 0.12 cm3, p = 0.014), gradient oscillatory number (0.0234 vs 0.0289, p = 0.023), invariant Q (-0.801 10-2/sec2 vs -0.124 10 2/sec2, p = 0.045) and higher aneurysm formation indicator (0.986 vs 0.963, p = 0.041) were significantly related to inside-pattern aneurysms when compared with outside-pattern aneurysms. CONCLUSIONS Inside-pattern aneurysms may have simpler flow patterns and less flow stagnation than outside-pattern aneurysms. CFD may be useful to characterize the hemostatic pattern of ruptured cerebral aneurysms. PMID- 27257838 TI - Surgery for meningioma in the elderly and long-term survival: comparison with an age- and sex-matched general population and with younger patients. AB - OBJECTIVE The purpose of this study was to compare long-term prognosis after meningioma surgery in elderly and younger patients as well as to compare survival of elderly patients with surgically treated meningioma to survival rates for the general population. METHODS Five hundred meningioma patients (median follow-up 90 months) who underwent surgery between 1994 and 2009 were subdivided into "elderly" (age >= 65 years, n = 162) and "younger" (age < 65 years, n = 338) groups for uni- and multivariate analyses. Mortality was compared with rates for the age- and sex-matched general population. RESULTS The median age at diagnosis was 71 in the elderly group and 51 years in the younger group. Sex, intracranial tumor location, grade of resection, radiotherapy, and histopathological subtypes were similar in the 2 groups. High-grade (WHO Grades II and III) and spinal tumors were more common in older patients than in younger patients (15% vs 8%, p = 0.017, and 12% vs 4%, p = 0.001, respectively). The progression-free interval (PFI) was similar in the 2 groups, whereas mortality at 3 months after surgery was higher and median overall survival (OS) was shorter in older patients (7%, 191 months) than in younger patients (1%, median not reached; HR 4.9, 95% CI 2.75 8.74; p < 0.001). Otherwise, the median OS in elderly patients did not differ from the anticipated general life expectancy (HR 1.03, 95% CI 0.70-1.50; p = 0.886). Within the older patient group, PFI was lower in patients with high-grade meningiomas (HR 24.74, 95% CI 4.23-144.66; p < 0.001) and after subtotal resection (HR 10.57, 95% CI 2.23-50.05; p = 0.003). Although extent of resection was independent of perioperative mortality, the median OS was longer after gross total resection than after subtotal resection (HR 2.7, 95% CI 1.09-6.69; p = 0.032). CONCLUSIONS Elderly patients with surgically treated meningioma do not suffer from impaired survival compared with the age-matched general population, and their PFI is similar to that of younger meningioma patients. These data help mitigate fears concerning surgical treatment of elderly patients in an aging society. PMID- 27257839 TI - Complication avoidance in laser interstitial thermal therapy: lessons learned. AB - OBJECTIVE Complications of laser interstitial thermal therapy (LITT) are underreported. The authors discuss how they have modified their technique in the context of technical and treatment-related adverse events. METHODS The Medtronic Visualase system was used in 49 procedures in 46 patients. Between 1 and 3 cooling catheters/laser fiber assemblies were placed, for a total of 62 implanted devices. Devices were placed using frameless stereotaxy (n = 3), frameless stereotaxy with intraoperative MRI (iMRI) (n = 9), iMRI under direct vision (n = 2), MRI alone (n = 1), or frame-based (n = 47) techniques. LITT was performed while monitoring MRI thermometry. Indications included brain tumors (n = 12), radiation necrosis (n = 2), filum terminale ependymoma (n = 1), mesial temporal lobe epilepsy (n = 21), corpus callosotomy for bifrontal epilepsy (n = 3), cavernoma (n = 1), and hypothalamic hamartomas (n = 6). RESULTS Some form of adverse event occurred in 11 (22.4%) of 49 procedures. These included 4 catheter malpositions, 3 intracranial hemorrhages, 3 cases of neurological deficit related to thermal injury, and 1 technical malfunction resulting in an aborted procedure. Of these, direct thermal injury was the only cause of prolonged neurological morbidity and occurred in 3 of 49 procedures. Use of frameless stereotaxy and increased numbers of devices were associated with significantly increased complication rates (p < 0.05). A number of procedural modifications were made to avoid complications, including the use of 1) frame-based catheter placement, a 1.8-mm alignment rod to create a track and titanium skull anchors for long trajectories to improve accuracy; 2) a narrow-gauge instrument for dural puncture and coregistration of contrast MRI with CT angiography to reduce intracranial hemorrhage; 3) general endotracheal anesthesia for posterior-placed skull anchors to reduce the likelihood of damage to the cooling catheter; 4) use of as few probes as possible to reduce complications overall; and 5) dose modification of thermal treatment and use of short (3-mm) diffusing tips to limit treatment when structures to be spared do not have intervening CSF spaces to act as heat sinks. CONCLUSIONS Laser ablation treatment may be used for a variety of neurosurgical procedures for patients with tumors and epilepsy. While catheter placement and thermal treatment may be associated with a range of suboptimal operative and postoperative courses, permanent neurological morbidity is less common. The authors' institutional experience illustrates a number of measures that may be taken to improve outcomes using this important new tool in the neurosurgical arsenal. PMID- 27257840 TI - Low flow velocity in the middle cerebral artery predicting infarction after bypass surgery in adult moyamoya disease. AB - OBJECTIVE Direct and indirect bypass surgeries are recognized as the most effective treatments for preventing further stroke in adults with moyamoya disease (MMD). However, the risk factors for postoperative infarction after bypass surgery for MMD are not well established. Therefore, the objective of this study was to investigate the risk factors for postoperative infarction. In particular, the authors sought to determine whether transcranial Doppler (TCD) ultrasonography measurements of mean flow velocity (MFV) in the middle cerebral artery (MCA) could predict postrevascularization infarction. METHODS The medical records of patients with MMD who underwent direct bypass surgery at the authors' institution between July 2012 and April 2015 were reviewed. The MFV in the MCA was measured with TCD ultrasonography and categorized as high (> 80 cm/sec), medium (40-80 cm/sec), and low (< 40 cm/sec). Postoperative MRI, including diffusion-weighted imaging, was performed for all patients within a week of their surgery. Angiographic findings were classified according to the Suzuki scale. Postrevascularization infarction was defined as any diffusion restriction on postoperative MRI scans. Postoperative neurological status was assessed through a clinical chart review, and the modified Rankin Scale was used to evaluate clinical outcomes. RESULTS Of 43 hemispheres in which bypass surgery for MMD was performed, 11 showed postrevascularization infarction. Ten of these hemispheres had low MFV and 1 had medium MFV in the ipsilateral MCA. In both univariate and multivariate analyses, a low MFV was associated with postrevascularization infarction (adjusted OR 109.2, 95% CI 1.9-6245.3). A low MFV was also statistically significantly associated with more advanced MMD stage (p = 0.02). CONCLUSIONS A low MFV in the ipsilateral MCA may predict postrevascularization infarction. Bypass surgery for MMD appears to be safe in early-stage MMD. Results of TCD ultrasonography provide clinical data on the hemodynamics in MMD patients before and after revascularization. PMID- 27257841 TI - Contralateral supraorbital keyhole approach to medial optic nerve lesions: an anatomoclinical study. AB - OBJECTIVE The authors describe the supraorbital keyhole approach to the contralateral medial optic nerve and tract, both in a series of cadaveric dissections and in 2 patients. They also discuss the indications and contraindications for this procedure. METHODS In 3 cadaver heads, bilateral supraorbital keyhole minicraniotomies were performed to expose the ipsilateral and contralateral optic nerves. The extent of exposure of the medial optic nerve was assessed. In 2 patients, a contralateral supraorbital keyhole approach was used to remove pathology of the contralateral medial optic nerve and tract. RESULTS The supraorbital keyhole craniotomy provided better exposure of the contralateral superomedial nerve than it did of the same portion of the ipsilateral nerve. In both patients gross-total resections of the pathology was achieved. CONCLUSIONS The authors demonstrate the suitability of the contralateral supraorbital keyhole approach for lesions involving the superomedial optic nerve. PMID- 27257842 TI - Letter to the Editor: Biases in estimation of overall survival in patients who underwent repeat resection of glioblastoma. PMID- 27257843 TI - Antibiotic prophylaxis for subdural and subgaleal drains. AB - OBJECTIVE The authors sought to determine the effects of eliminating the use of prolonged prophylactic systemic antibiotics (PPSAs) in patients with subdural and subgaleal drains. METHODS Using a retrospective database, the authors collected data for patients over the age of 17 years who had undergone cranial surgery at their institution between December 2013 and July 2014 (PPSAs period) or between December 2014 and July 2015 (non-PPSAs period) and had subdural or subgaleal drains left in place postoperatively. RESULTS One hundred five patients in the PPSAs period and 80 in the non-PPSAs period were identified. The discontinuation of PPSAs did not result in an increase in the frequency of surgical site infection (SSI). The frequency of Clostridium difficile (CDI) and the growth of resistant bacteria were reduced in the non-PPSAs period in comparison with the PPSAs period. In the 8 months after the drain prophylaxis protocol was changed, $93,194.63 were saved in the costs of antibiotics and complications related to antibiotics. CONCLUSIONS After discontinuing PPSAs for patients with subdural or subgaleal drains at their institution, the authors did not observe an increase in the frequency of SSI. They did, however, note a decrease in the frequency of CDI and the growth of resistant organisms. It appears that not only can patients in this population do without PPSAs, but also that complications are avoided when antibiotic use is limited to 24 hours after surgery. PMID- 27257844 TI - The association between adherence to the New Nordic Diet and diet quality. AB - BACKGROUND: Previous studies have reported a positive association between scoring on healthy Nordic diet scales and the intake of healthy foods and nutrients, and also with higher intake of meat, sweets, cakes, and energy in general. These studies have used the same food frequency questionnaire (FFQ) responses for constructing the diet score as for calculating intakes of foods and nutrients. Thus, it is not clear whether the coexistence of healthy and less healthy dietary aspects among adherers to Nordic diets would occur even though separate methods were applied for exploring these relations. OBJECTIVE: To assess the association between adherence to the New Nordic Diet (NND), derived from an FFQ, and diet quality, determined from two 24-h dietary recall interviews. DESIGN: In total, 65 parents of toddlers in Southern Norway answered the NND FFQ and two 24-h dietary recall interviews. NND adherence was determined from the FFQ and categorized into low, medium, and high adherence. The two 24-h recalls provided data for the intake of specific foods and nutrients, selected on the basis of the Norwegian food-based guidelines as an indicator of a healthy diet. The Kruskal-Wallis test was used for assessing differences in food and nutrient intake across NND groups. RESULTS: High NND adherence derived from FFQ was associated with a high intake of fruits (p=0.004) and fiber (p=0.02), and a low intake of meat (p=0.004) and margarines (p=0.05), derived from recalls. A larger proportion of high NND adherers (68%) complied with the national dietary recommendation targeting meat intake compared with low NND adherers (29%) (p=0.04). CONCLUSION: The present study showed that higher NND adherence measured with FFQ was associated with a higher intake of selected healthy foods and nutrients, measured with recalls. However, a higher intake of meat, sweets, and energy, as earlier reported, was not observed. PMID- 27257845 TI - Interference effect of oral administration of mulberry branch bark powder on the incidence of type II diabetes in mice induced by streptozotocin. AB - BACKGROUND: Diabetes is a group of metabolic diseases that has become a global health problem worldwide. Many researchers have found that mulberry branches have a hypoglycemic effect, but there have been few studies or investigations regarding the use of mulberry branches to prevent the incidence of diabetes. OBJECTIVE: This study aimed to investigate the potential preventive effect of mulberry branch bark powder (MBBP) from Morus multicaulis L against type II diabetes in mice induced by streptozotocin (STZ). DESIGN: The normal mice were fed a diet containing 2.5, 5.0, and 10.0%, MBBP, respectively, for 2 weeks. After that, STZ (100 mg/kg) was injected into the caudal vein of these mice. These mice continued to be fed the same diet, and the fasting blood glucose (FBG) levels were monitored on the 17th and 21st days. RESULTS: Oral administration of MBBP could effectively inhibit weight loss and maintain the FBG level. The incidence of diabetes in mice was almost inhibited by treatment with 10% MBBP. MBBP could also maintain the original antioxidant capacity and regulate the lipid metabolism in mice. An immunohistochemical assay showed that MBBP could prevent the injury of the insulin-secreting islet beta cells induced by STZ. RT-PCR also confirmed that the mRNA expression of the genes PI3K, Pdk1, Akt, and FoxO1, which were involved in the PI3K/Akt signaling pathway, hardly suffered from STZ in the 10% MBBP-dose group. CONCLUSIONS: Our results indicate that powdered mulberry branch bark has a powerful anti-diabetic effect. These results clearly illustrated that MBBP has a potential use as a health food additive in the prevention of diabetes. PMID- 27257846 TI - Photochemistry of Nitrophenol Molecules and Clusters: Intra- vs Intermolecular Hydrogen Bond Dynamics. AB - We investigate both experimentally and theoretically the structure and photodynamics of nitrophenol molecules and clusters, addressing the question how the molecular photodynamics can be controlled by specific inter- and intramolecular interactions. Using quantum chemical calculations, we demonstrate the structural and energetic differences between clusters of 2-nitrophenol and 4 nitrophenol, using phenol as a reference system. The calculated structures are supported by mass spectrometry. The mass spectra of 2-nitrophenol clusters provide an evidence for a stacked structure compared to a strong O-H...O hydrogen bonding for 4-nitrophenol aggregates. We further investigate the photodynamics of nitrophenol molecules and clusters by means of velocity map imaging of the H fragment generated upon 243 nm photodissociation. The experiments are complemented by ab initio calculations which demonstrate distinct photophysics of phenol, 2-nitrophenol, 4-nitrophenol. The measured H-fragment kinetic energy distributions (KEDs) from 2-nitrophenol molecules are compared to the KEDs from phenol. The comparison points to the intramolecular O-H...O hydrogen bond in 2 nitrophenol, stimulating fast internal conversion into the ground electronic state. This reaction channel is marked by exclusive appearance of slow statistical hydrogen fragments in 2-nitrophenol, which contrasts with fast hydrogen atoms observed for phenol. The photodissociation of 2-nitrophenol clusters yields a fraction of H-fragments with higher kinetic energies than the isolated molecules. These fragments originate from the caging effect in the clusters leading to multiphoton dissociation of molecules excited by the previous photons. We also propose a new ab initio based value for the O-H bond dissociation enthalpy in 2-nitrophenol (4.25 eV), which is in excellent agreement with the maximum measured H-fragment kinetic energy. PMID- 27257847 TI - Two-Dimensional Titanium Carbide/RGO Composite for High-Performance Supercapacitors. AB - Ti3C2Tx, a 2D titanium carbide in the MXenes family, is obtained from Ti3AlC2 through selective etching of the Al layer. Due to its good conductivity and high volumetric capacitance, Ti3C2Tx is regarded as a promising candidate for supercapacitors. In this paper, the fabrication of Ti3C2Tx/RGO composites with different proportions of Ti3C2Tx and RGO is reported, in which RGO acts as a conductive "bridge" to connect different Ti3C2Tx blocks and a matrix to alleviate the volume change during charge/discharge process. In addition, RGO nanosheets can serve as a second nanoscale current collector and support as well for the electrode. The electrochemical performance of the as-fabricated Ti3C2Tx/RGO electrodes, characterized by CV, GCD, and EIS, are also reported. A highest specific capacitance (Cs) of 154.3 F/g at 2 A/g is obtained at the Ti3C2Tx: RGO weight ratio of 7:1 combined with an outstanding capacity retention (124.7 F/g) after 6000 cycles at 4 A/g. PMID- 27257848 TI - Comprehensive Vibrational Spectroscopic Investigation of trans,trans,trans [Pt(N3)2(OH)2(py)2], a Pt(IV) Diazido Anticancer Prodrug Candidate. AB - We report a detailed study of a promising photoactivatable metal-based anticancer prodrug candidate, trans,trans,trans-[Pt(N3)2(OH)2(py)2] (C1; py = pyridine), using vibrational spectroscopic techniques. Attenuated total reflection Fourier transform infrared (ATR-FTIR), Raman, and synchrotron radiation far-IR (SR-FIR) spectroscopies were applied to obtain highly resolved ligand and Pt-ligand vibrations for C1 and its precursors (trans-[Pt(N3)2(py)2] (C2) and trans [PtCl2(py)2] (C3)). Distinct IR- and Raman-active vibrational modes were assigned with the aid of density functional theory calculations, and trends in the frequency shifts as a function of changing Pt coordination environment were determined and detailed for the first time. The data provide the ligand and Pt ligand (azide, hydroxide, pyridine) vibrational signatures for C1 in the mid- and far-IR region, which will provide a basis for the better understanding of the interaction of C1 with biomolecules. PMID- 27257849 TI - Premature cardiovascular disease following a history of hypertensive disorder of pregnancy. AB - BACKGROUND: Following an episode of hypertensive disorder of pregnancy (HDP) women have an increased risk of cardiovascular disease over their lifetime. At the time of acute coronary syndrome we compared clinical information between women with and without a history of hypertension in pregnancy to gain further insight into the pathophysiology of cardiovascular disease in this population. METHODS: GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-PRemature Acute Coronary SYdrome) is a prospective multicenter study, with recruitment between January 2009 and April 2013, including 242 parous women with premature acute coronary syndrome. RESULTS: The median age was 50years (IQR 6) and HDP was common; 43 (17.8%) women had prior gestational hypertension, 33 (13.6%) preeclampsia and 166 (68.6%) a prior normotensive pregnancy. Women with a history of HDP commonly had chronic hypertension and diabetes and those presenting with ST-elevation myocardial infarction were more likely to have a history of preeclampsia (aOR 3.12, 95% CI 1.22-8.01) than were women with prior normotensive pregnancies. Neither gestational hypertension (aOR 1.40, 95% CI 0.60-3.26) nor preeclampsia (aOR 0.63, 95% CI 0.23-1.74) was associated with a higher composite risk of three-vessel, left main or proximal left anterior descending coronary disease. CONCLUSION: In this study of women with premature cardiovascular disease, ST-elevation myocardial infarction was associated with a history of preeclampsia possibly because of persistent endothelial dysfunction. High-risk coronary lesions on angiography did not appear to have an association with preeclampsia or gestational hypertension despite a high burden of traditional risk factors. PMID- 27257851 TI - Decreased admission serum albumin level is an independent predictor of long-term mortality in hospital survivors of acute myocardial infarction. Soroka Acute Myocardial Infarction II (SAMI-II) project. AB - BACKGROUND: Decreased serum albumin level (SAL) was reported to be associated with increased risk of cardiovascular events and short term-mortality in patients with acute myocardial infarction (AMI). OBJECTIVES: To evaluate the association between SAL and long-term mortality in AMI hospital survivors. METHODS: Retrospective analysis of patients admitted in a tertiary medical center for AMI 2002-2012 and discharged alive. EXCLUSION CRITERIA: active infections, inflammatory diseases, significant liver or kidney failure, malignancy, ejection fraction <20%, severe heart valvular-disease and missing SAL. SAL was categorized as following: <3.4, 3.4-3.7, 3.7-3.9, 3.9-4.1 and >4.1g/dL. The primary outcome was all-cause mortality for up-to 10-years post-AMI. RESULTS: Out of 12,535 patients, 8750 were included. Patients with reduced SAL were older, higher rate of women, increased prevalence of severe left ventricular dysfunction, chronic renal failure, diabetes mellitus and ST-elevation AMI, 3-vessel coronary artery disease, and in-hospital complications. While the prevalence of chronic ischemic coronary disease, dyslipidemia, smokers and obesity, was lower. Mortality rates throughout the follow-up period increased as SAL decreased with 17.6%, 24%, 28.5%, 38.6%, and 57.5% for SAL of >4.1, 3.9-4.1, 3.7-3.9, 3.4-3.7 and <3.4g/dL respectively (p-for-trend <0.001). Using the SAL category of >4.1g/dL as the reference group, Adjusted Hazard Ratio values were 1.14 (p=0.107), 1.23 (p=0.007), 1.39 (p<0.001) and 1.70 (p<0.001) for the SAL categories of 3.9-4.1, 3.7-3.9, 3.4-3.7 and <3.4g/dL respectively. CONCLUSIONS: Decreased SAL on admission, including levels within "normal" clinical range, is significantly associated with long-term all-cause mortality in hospital survivors of AMI with a "dose-response" type association. PMID- 27257850 TI - The Fontan epidemic: Population projections from the Australia and New Zealand Fontan Registry. AB - BACKGROUND: The number and age demographic of the future Fontan population is unknown. METHODS: Population projections were calculated probabilistically using microsimulation. Mortality hazard rates for each Fontan recipient were calculated from survivorship of 1353 Fontan recipients in the Australia and New Zealand Fontan Registry, based on Fontan type, age at Fontan, gender and morphology. Projected rates of new Fontan procedures were generated from historical rates of Fontan procedures per population births. RESULTS: At the end of 2014, the living Fontan population of Australia and New Zealand was 1265 people from an Australian and New Zealand regional population of 28 million (4.5 per 100,000 population). Of those, 165 (13%) received an atrio-pulmonary (AP) procedure, 262 (21%) a lateral tunnel (LT) procedure and 838 (66%) an extra-cardiac conduit (ECC) procedure. This population is expected to grow to 1917 (95% CI: 1846: 1986) by 2025 (5.8 per 100,000 population), with 149 (8%) AP procedures, 254 (13%) LT procedures, and 1514 (79%) ECC procedures. By 2045, the living Fontan population is expected to reach 2986 (95% CI: 2877: 3085; 7.2 per 100,000 population). The average age of the Fontan population is expected to increase from 18years in 2014 to 23years (95% CI: 22-23) by 2025, and 31years (95% CI: 30-31) by 2045. CONCLUSION: The Australian and New Zealand population of patients alive after a Fontan procedure will double over the next 20years increasing the demand for heart-failure services and cardiac transplantation. Greater consideration for the needs of this mostly adult Fontan population will be necessary. PMID- 27257852 TI - Changes in plasma hormones and heart rate variability in patients receiving the cardiotoxic anti-cancer agent bevacizumab. PMID- 27257853 TI - Toward Analysis of Proteins in Single Cells: A Quantitative Approach Employing Isobaric Tags with MALDI Mass Spectrometry Realized with a Microfluidic Platform. AB - Protein identification and quantification in individual cells is essential to understand biological processes such as those involved in cell apoptosis, cancer, biomarker discovery, disease diagnostics, pathology, or therapy. Compared with present single cell genome analysis, probing the protein content of single cells has been hampered by the lack of a protein amplification technique. Here, we report the development of a quantitative mass spectrometric approach combined with microfluidic technology reaching the detection sensitivity of high abundant proteins in single cells. A microfluidic platform with a series of chambers and valves, ensuring a set of defined wells for absolute quantification of targeted proteins, was developed and combined with isotopic labeling strategies employing isobaric tags for relative and absolute quantitation (iTRAQ)-labels. To this aim, we adapted iTRAQ labeling to an on-chip protocol. Simultaneous protein digestion and labeling performed on the microfluidic platform rendered the labeling strategy compatible with all necessary manipulation steps on-chip, including the matrix delivery for MALDI-TOF analysis. We demonstrate this approach with the apoptosis related protein Bcl-2 and quantitatively assess the number of Bcl-2 molecules detected. We anticipate that this approach will eventually allow quantification of protein expression on the single cell level. PMID- 27257855 TI - Novel Concentrated Li[(FSO2)(n-C4F9SO2)N]-Based Ether Electrolyte for Superior Stability of Metallic Lithium Anode. AB - Lithium (fluorosulfonyl)(n-nonafluorobutanesulfonyl)imide [Li[(FSO2)(n-C4F9SO2)N] (LiFNFSI)] is investigated as a conducting salt, which can form a relatively stable solid-electrolyte-interphase film in concentrated ether electrolyte to achieve favorable protection for lithium metal anodes. Li|Cu and Li|Li cells with concentrated LiFNFSI-based electrolyte have been demonstrated to display high average Coulombic efficiency (~97%) and excellent cycling stability (over 1,000 h) of metallic lithium anodes, compared to concentrated lithium bis(trifluoromethanesulfonyl)imide [Li[N(SO2CF3)2] (LiTFSI)]-based electrolyte. The morphologies and compositions of the lithium-metal anode surface are also comparatively analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy, respectively. Moreover, superior electrochemical performance in the concentrated LiFNFSI-based electrolyte for Li|LiFePO4 cells is also presented herein. These results indicate that concentrated LiFNFSI-based electrolyte is a promising candidate for metallic lithium rechargeable batteries. PMID- 27257856 TI - Compassion and chronic pain. PMID- 27257854 TI - MiR-15a/16 Regulates Apoptosis of Lung Epithelial Cells after Oxidative Stress. AB - Lung epithelial cell apoptosis is an important feature of hyperoxia-induced lung injury. Death receptor-associated extrinsic pathway and mitochondria-associated intrinsic pathway both mediate the development of lung epithelial cell apoptosis. Despite decades of research, molecular mechanisms of hyperoxia-induced epithelial cell apoptosis remain incompletely understood. Here we report a novel regulatory paradigm in response to hyperoxia-associated oxidative stress. Hyperoxia markedly up-regulated miR-15a/16 levels in lung epithelial cells, broncho-alveolar lavage fluid (BALF) and lung tissue. This effect was mediated by hyperoxia-induced reactive oxygen species (ROS). Functionally, miR-15a/16 inhibitors induced caspase 3-mediated lung epithelial cell apoptosis, in the presence of hyperoxia. MiR-15a/16 inhibitors robustly enhanced FADD level and down-regulated Bcl-2 expression. Consistently, cleaved caspase 8 and 9 were highly induced in the miR 15a/16 deficient cells, after hyperoxia. Using airway epithelial cell specific, miR-15a/16-/- mice, we found that Bcl-2 significantly reduced in lung epithelial cells in vivo after hyperoxia. In contrast, caspase 3, 8 and Bcl-2 associated death promoter (BAD) were highly elevated in the miR-15a/16-/- epithelial cells in vivo. Interestingly, in lung epithelial malignant cells, rather than benign cells, deletion of miR-15a/16 prevented apoptosis. Furthermore, deletion of miR 15a/16 in macrophages also prohibited apoptosis, opposite to what we have found in normal lung epithelial cells. Taken together, our data suggested that miR 15a/16 may exert differential roles in different cell types. MiR-15a/16 deficiency result in lung epithelial cell apoptosis in response to hyperoxia, via modulating both intrinsic and extrinsic apoptosis pathways. PMID- 27257857 TI - The Pain Course: exploring predictors of clinical response to an Internet delivered pain management program. AB - There is significant interest in the potential of Internet-delivered pain management programs for adults with chronic pain. Understanding the characteristics of people who do and do not benefit from Internet-delivered programs will help to guide their safe and effective use. Using a large sample from a previous randomised controlled trial of an established Internet-delivered pain management program, the Pain Course, this study (n = 463) examined whether several demographic, clinical, psychological, and treatment-related variables could be used to predict clinical response in levels of disability, depression, anxiety, or average pain. Multiple univariate and multivariate stepwise logistic regressions were used to identify unique predictors of clinical improvement, which, consistent with recommendations, was defined as a >=30% reduction in symptoms or difficulties from baseline. Several unique predictors of clinical improvement were found. However, no particularly decisive or dominant predictors emerged that were common across time points or across the outcome domains. Reflecting this, the identified predictors explained only 18.1%, 13.7%, 7.6%, and 9.5% of the variance in the likelihood of making a clinical improvement in disability, depression, anxiety, and average pain levels, respectively. The current findings suggest that a broad range of patients may benefit from emerging Internet-delivered pain management programs and that it may not be possible to predict who will or will not benefit on the basis of patients' demographic, clinical, and psychological characteristics. PMID- 27257858 TI - Back schools for the treatment of chronic low back pain: possibility of benefit but no convincing evidence after 47 years of research-systematic review and meta analysis. AB - Back schools are interventions that comprise exercise and education components. We aimed to systematically review the randomized controlled trial evidence on back schools for the treatment of chronic low back pain. By searching MEDLINE, Embase, and Cochrane Central as well as bibliographies, we identified 31 studies for inclusion in our systematic review and 5 of these for inclusion in meta analyses. Meta-analyses for pain scores and functional outcomes revealed statistical superiority of back schools vs no intervention for some comparisons but not others. No meta-analysis was feasible for the comparison of back schools vs other active treatments. Adverse events were poorly reported so that no reliable conclusions regarding the safety of back schools can be drawn, although some limited reassurance in this regard may be derived from the fact that few adverse events and no serious adverse events were reported in the back school groups in the studies that did report on safety. Overall, the evidence base for the use of back schools to treat chronic low back pain is weak; in nearly a half century since back schools were first trialled, no unequivocal evidence of benefit has emerged. PMID- 27257859 TI - Mindfulness-based stress reduction and cognitive behavioral therapy for chronic low back pain: similar effects on mindfulness, catastrophizing, self-efficacy, and acceptance in a randomized controlled trial. AB - Cognitive behavioral therapy (CBT) is believed to improve chronic pain problems by decreasing patient catastrophizing and increasing patient self-efficacy for managing pain. Mindfulness-based stress reduction (MBSR) is believed to benefit patients with chronic pain by increasing mindfulness and pain acceptance. However, little is known about how these therapeutic mechanism variables relate to each other or whether they are differentially impacted by MBSR vs CBT. In a randomized controlled trial comparing MBSR, CBT, and usual care (UC) for adults aged 20 to 70 years with chronic low back pain (N = 342), we examined (1) baseline relationships among measures of catastrophizing, self-efficacy, acceptance, and mindfulness and (2) changes on these measures in the 3 treatment groups. At baseline, catastrophizing was associated negatively with self efficacy, acceptance, and 3 aspects of mindfulness (nonreactivity, nonjudging, and acting with awareness; all P values <0.01). Acceptance was associated positively with self-efficacy (P < 0.01) and mindfulness (P values <0.05) measures. Catastrophizing decreased slightly more posttreatment with MBSR than with CBT or UC (omnibus P = 0.002). Both treatments were effective compared with UC in decreasing catastrophizing at 52 weeks (omnibus P = 0.001). In both the entire randomized sample and the subsample of participants who attended >=6 of the 8 MBSR or CBT sessions, differences between MBSR and CBT at up to 52 weeks were few, small in size, and of questionable clinical meaningfulness. The results indicate overlap across measures of catastrophizing, self-efficacy, acceptance, and mindfulness and similar effects of MBSR and CBT on these measures among individuals with chronic low back pain. PMID- 27257861 TI - Subspecific Differentiation Events of Montane Stag Beetles (Coleoptera, Lucanidae) Endemic to Formosa Island. AB - Taxonomic debates have been carrying on for decades over Formosan stag beetles, which consist of a high proportion of endemic species and subspecies featuring morphological variations associated with local adaptation. With the influence of periodical Pleistocene glaciations and the presence of several mountain ranges, the genetic differentiation and taxonomic recognition, within this medium-size island, of two endemic subspecies for each of four montane stag beetles, i.e. Lucanus ogakii, L. kanoi, Prismognathus davidis, and Neolucanus doro, has been an appealing issue. Based on monophyletic lineages and population structure, possible divergent scenarios have been proposed to clarify the subspecific status for each of the above mentioned stag beetles. Phylogenetic inferences based on COI+16S rDNA+28S rDNA of 240 Formosan lucanids have confirmed most species are monophyletic groups; and the intraspecific (<2%) and interspecific (>2%) genetic distances of the two mitochondrial genes could be applied concordantly for taxonomic identification. On account of Bayesian-based species delimitation, geographic distribution, population structure, and sequence divergences, the subspecific status for L. ogakii, L. kanoi, and Pri. davidis are congruent with their geographic distribution in this island; and the calibration time based on the mitochondrial genes shows the subspecific split events occurred 0.7-1 million years ago. In addition, a more complicated scenario, i.e. genetic differentiation including introgression/hybridization events, might have occurred among L. ogakii, L. kanoi, and L. maculifemoratus. The geological effects of mountain hindrance accompanied by periodical glaciations could have been vital in leading to the geographical subspecific differentiation of these montane stag beetles. PMID- 27257862 TI - Immunoadjuvant Properties of the Rho Activating Factor CNF1 in Prophylactic and Curative Vaccination against Leishmania infantum. AB - There is a need to develop new effective immunoadjuvants for prophylactic or therapeutic vaccines against intracellular pathogens. The activation of Rho GTPases by bacterial cytotoxic necrotizing factor 1 (CNF1) elicits humoral protective responses against protein antigens. Here, we set out to investigate whether CNF1 activity initiates humoral immunity against co-administered parasite antigens and anti-microbial immune signaling. We report that co-administration of wild-type (WT) CNF1 with Leishmania (L.) promastigote antigens at the nasal mucosa triggered prophylactic and curative vaccine responses against this parasite. Vaccination of the mucosa with promastigote lysate antigens combined with WT CNF1 conferred protection against high inoculum L. infantum infection, which reached 82% in the spleen. Immune parameter analysis by antigen recall indicated robust T-helper (Th)1 polarization of immune memory cells, with high IL 2 and IFN-gamma production combined with decreased IL-4 production. Additionally, we explored the curative effect of WT CNF1 on previously infected animals. We observed that PL combined with WT CNF1, but not the inactive C866S mutant CNF1 (mCNF1), induced a 58% decrease in the parasite burden in the spleen. PMID- 27257863 TI - MRI Based Preterm White Matter Injury Classification: The Importance of Sequential Imaging in Determining Severity of Injury. AB - BACKGROUND: The evolution of non-hemorrhagic white matter injury (WMI) based on sequential magnetic resonance imaging (MRI) has not been well studied. Our aim was to describe sequential MRI findings in preterm infants with non-hemorrhagic WMI and to develop an MRI classification system for preterm WMI based on these findings. METHODS: Eighty-two preterm infants (gestation <=35 weeks) were retrospectively included. WMI was diagnosed and classified based on sequential cranial ultrasound (cUS) and confirmed on MRI. RESULTS: 138 MRIs were obtained at three time-points: early (<2 weeks; n = 32), mid (2-6 weeks; n = 30) and term equivalent age (TEA; n = 76). 63 infants (77%) had 2 MRIs during the neonatal period. WMI was non-cystic in 35 and cystic in 47 infants. In infants with cystic WMI early MRI showed extensive restricted diffusion abnormalities, cysts were already present in 3 infants; mid MRI showed focal or extensive cysts, without acute diffusion changes. A significant reduction in the size and/or extent of the cysts was observed in 32% of the infants between early/mid and TEA MRI. In 4/9 infants previously seen focal cysts were no longer identified at TEA. All infants with cystic WMI showed >=2 additional findings at TEA: significant reduction in WM volume, mild-moderate irregular ventriculomegaly, several areas of increased signal intensity on T1-weighted-images, abnormal myelination of the PLIC, small thalami. CONCLUSION: In infants with extensive WM cysts at 2-6 weeks, cysts may be reduced in number or may even no longer be seen at TEA. A single MRI at TEA, without taking sequential cUS data and pre-TEA MRI findings into account, may underestimate the extent of WMI; based on these results we propose a new MRI classification for preterm non-hemorrhagic WMI. PMID- 27257864 TI - Measurement of Electroretinograms and Visually Evoked Potentials in Awake Moving Mice. AB - The development of new treatments for intractable retinal diseases requires reliable functional assessment tools for animal models. In vivo measurements of neural activity within visual pathways, including electroretinogram (ERG) and visually evoked potential (VEP) recordings, are commonly used for such purposes. In mice, the ERG and VEPs are usually recorded under general anesthesia, a state that may alter sensory transduction and neurotransmission, but seldom in awake freely moving mice. Therefore, it remains unknown whether the electrophysiological assessment of anesthetized mice accurately reflects the physiological function of the visual pathway. Herein, we describe a novel method to record the ERG and VEPs simultaneously in freely moving mice by immobilizing the head using a custom-built restraining device and placing a rotatable cylinder underneath to allow free running or walking during recording. Injection of the commonly used anesthetic mixture xylazine plus ketamine increased and delayed ERG oscillatory potentials by an average of 67.5% and 36.3%, respectively, compared to unanesthetized mice, while having minimal effects on the a-wave and b-wave. Similarly, components of the VEP were enhanced and delayed by up to 300.2% and 39.3%, respectively, in anesthetized mice. Our method for electrophysiological recording in conscious mice is a sensitive and robust means to assess visual function. It uses a conventional electrophysiological recording system and a simple platform that can be built in any laboratory at low cost. Measurements using this method provide objective indices of mouse visual function with high precision and stability, unaffected by anesthetics. PMID- 27257865 TI - Reduction of Coronary Motion Artifacts in Prospectively Electrocardiography-Gated Coronary Computed Tomography Angiography Using Monochromatic Imaging at Various Energy Levels in Combination With a Motion Correction Algorithm on Single-Source Fast Tube Voltage Switching Dual-Energy Computed Tomography: A Phantom Experiment. AB - OBJECTIVES: The aim of this study was to assess the effect of monochromatic imaging at various energy levels in combination with a motion correction algorithm (MCA) in single-source dual-energy coronary computed tomography angiography (CCTA) with fast switching of tube voltage on the reduction of coronary motion artifacts (CMA) in a phantom setting. MATERIALS AND METHODS: Using this dual-energy computed tomography technique with a phantom comprising models of coronary vessels filled with contrast medium and pulsating at constant heart rates of 60 to 100 beats per minute, we reconstructed monochromatic images of CCTA obtained at 50 to 90 keV with and without use of MCA. Cardiac motion was modeled by simulating the in vivo time-volume curve of the left ventricle. Two independent readers graded CMA in 9 coronary segments using a 5-point scale (1, poor; 3 to 5, interpretable; 5, excellent). At each heart rate, we compared the average score of CMA between images obtained at 50 to 90 keV with and without use of MCA using Wilcoxon signed rank test, and we compared the score among images obtained at 50 to 90 keV with use of MCA using Kruskal-Wallis and post hoc tests. We also compared the percentages of image interpretability and improvement in image interpretability among images obtained at 50 to 90 keV with use of MCA. RESULTS: With the use of MCA, the average score of CMA was significantly higher for images obtained at each energy level from 50 to 70 keV (P < 0.05) and was comparable at 80 and 90 keV, and it was comparable among those obtained at 50 to 70 keV. With its use, the percentages of image interpretability were similarly high at 50 to 70 keV at 60 to 80 beats per minute (78%-100%), and they were higher at 50 to 60 keV (72%-83%) than at 70 keV at 90 to 100 beats per minute (50%-56%). The percentages of improved image interpretability with MCA were similarly high at 50 to 70 keV at 60 to 80 beats per minute (56%-100%), and they were higher at 50 to 60 keV (62%-77%) than at 70 keV at 90 to 100 beats per minute (36%-43%). The percentages of image interpretability and improved image interpretability with MCA were insufficient at 80 and 90 keV. CONCLUSIONS: Coronary motion artifacts were significantly reduced in images of monochromatic CCTA obtained at 50 to 70 keV in combination with MCA compared with those obtained without MCA, and the percentages of image interpretability and improved image interpretability with use of MCA were relatively high at 50 to 70 keV, and particularly at 50 to 60 keV, even at 90 to 100 beats per minute. PMID- 27257866 TI - Morphological and Quantitative 7 T MRI of Hip Cartilage Transplants in Comparison to 3 T-Initial Experiences. AB - OBJECTIVES: The aims of this study were to evaluate morphological and quantitative 7 T magnetic resonance imaging (MRI) hip sequences in patients after acetabular cartilage transplantation and to compare image quality with 3 T MRI. MATERIALS AND METHODS: Following approval from the local institutional ethics committee and signing informed consent, 9 patients with history of autologous acetabular cartilage transplantation were imaged at 7 T and 3 T MRI. Sequences (3 dimensional dual echo steady state, 3-dimensional T1 volume interpolated breath hold examination, sagittal proton density [PD] turbo spin echo and coronal fat saturated PD turbo spin echo, sagittal T1 mapping in dual flip angle technique, and multiecho spin echo/gradient echo sequences for T2 and T2* mapping) were applied after the intravenous application of Gd-DTPA according to a protocol for delayed gadolinium-enhanced MRI of cartilage and manual B1 shimming at 7 T. Images were compared intraindividually regarding image quality and assessability of cartilage structures using 5-point scales (1 = 3 T clearly superior, 5 = 7 T clearly superior) in consensus with 2 radiologists. Contrast ratios were calculated between articular cartilage, joint fluid, and subchondral bone. An adapted MOCART (MR observation of cartilage repair tissue) score was assessed independently at 3 T and 7 T. Relaxation times were measured in the transplanted acetabular region and in 2 reference regions by 2 readers independently to calculate interreader reliability. Statistical significances of field strength comparisons were calculated using Student t test and t test for dependent measurements. RESULTS: A 7 T MRI was superior to 3 T MRI in the majority of the sequences regarding subjective ratings. Furthermore, 7 T yielded comparable or better contrast ratios compared with 3 T. The criteria of the MOCART score matched totally at 3 T and 7 T, apart from the signal intensity of the repair tissue in PDw, which was rated higher at 7 T in 5 patients. Interreader reliability of all relaxation times was excellent. T1 and T2* relaxation times were significantly shorter at 7 T compared with 3 T. T2 relaxation times were longer at 7 T compared with 3 T without statistical significance. No significant difference could be seen when comparing the relaxation ratios (relaxation times after standardization to reference regions) of the cartilage transplant between the 2 field strengths. CONCLUSIONS: This study shows the feasibility of morphological and quantitative 7 T hip MRI in patients after acetabular cartilage transplantation and its predominant superiority regarding image quality, assessment of cartilage transplants, and contrast over 3 T MRI. To compare relaxation times between the field strengths, the calculation of intraindividual ratios is recommended. PMID- 27257867 TI - Pur-Alpha Induces JCV Gene Expression and Viral Replication by Suppressing SRSF1 in Glial Cells. AB - OBJECTIVE: PML is a rare and fatal demyelinating disease of the CNS caused by the human polyomavirus, JC virus (JCV), which occurs in AIDS patients and those on immunosuppressive monoclonal antibody therapies (mAbs). We sought to identify mechanisms that could stimulate reactivation of JCV in a cell culture model system and targeted pathways which could affect early gene transcription and JCV T-antigen production, which are key steps of the viral life cycle for blocking reactivation of JCV. Two important regulatory partners we have previously identified for T-antigen include Pur-alpha and SRSF1 (SF2/ASF). SRSF1, an alternative splicing factor, is a potential regulator of JCV whose overexpression in glial cells strongly suppresses viral gene expression and replication. Pur alpha has been most extensively characterized as a sequence-specific DNA- and RNA binding protein which directs both viral gene transcription and mRNA translation, and is a potent inducer of the JCV early promoter through binding to T-antigen. METHODS AND RESULTS: Pur-alpha and SRSF1 both act directly as transcriptional regulators of the JCV promoter and here we have observed that Pur-alpha is capable of ameliorating SRSF1-mediated suppression of JCV gene expression and viral replication. Interestingly, Pur-alpha exerted its effect by suppressing SRSF1 at both the protein and mRNA levels in glial cells suggesting this effect can occur independent of T-antigen. Pur-alpha and SRSF1 were both localized to oligodendrocyte inclusion bodies by immunohistochemistry in brain sections from patients with HIV-1 associated PML. Interestingly, inclusion bodies were typically positive for either Pur-alpha or SRSF1, though some cells appeared to be positive for both proteins. CONCLUSIONS: Taken together, these results indicate the presence of an antagonistic interaction between these two proteins in regulating of JCV gene expression and viral replication and suggests that they play an important role during viral reactivation leading to development of PML. PMID- 27257868 TI - Intrinsic Radiosensitivity and Cellular Characterization of 27 Canine Cancer Cell Lines. AB - Canine cancer cell lines have progressively been developed, but are still underused resources for radiation biology research. Measurement of the cellular intrinsic radiosensitivity is important because understanding the difference may provide a framework for further elucidating profiles for prediction of radiation therapy response. Our studies have focused on characterizing diverse canine cancer cell lines in vitro and understanding parameters that might contribute to intrinsic radiosensitivity. First, intrinsic radiosensitivity of 27 canine cancer cell lines derived from ten tumor types was determined using a clonogenic assay. The 27 cell lines had varying radiosensitivities regardless tumor type (survival fraction at 2 Gy, SF2 = 0.19-0.93). In order to understand parameters that might contribute to intrinsic radiosensitivity, we evaluated the relationships of cellular radiosensitivity with basic cellular characteristics of the cell lines. There was no significant correlation of SF2 with S-phase fraction, doubling time, chromosome number, ploidy, or number of metacentric chromosomes, while there was a statistically significant correlation between SF2 and plating efficiency. Next, we selected the five most radiosensitive cell lines as the radiosensitive group and the five most radioresistant cell lines as the radioresistant group. Then, we evaluated known parameters for cell killing by ionizing radiation, including radiation-induced DNA double strand break (DSB) repair and apoptosis, in the radiosensitive group as compared to the radioresistant group. High levels of residual gamma-H2AX foci at the sites of DSBs were present in the four out of the five radiosensitive canine cancer cell lines. Our studies suggested that substantial differences in intrinsic radiosensitivity exist in canine cancer cell lines, and radiation-induced DSB repair was related to radiosensitivity, which is consistent with previous human studies. These data may assist further investigations focusing on the detection of DSB for predicting individual response to radiation therapy for dogs, regardless of tumor type. PMID- 27257869 TI - Personalized treatment approach to gastroenteropancreatic neuroendocrine tumors: a medical oncologist's perspective. AB - The medical management of gastroenteropancreatic neuroendocrine tumors involves treatment of symptomatic disease related to hormone secretions or bulky unresectable metastatic disease. Combining gallium DOTA with fluorine-18 fluorodeoxyglucose-PET along with histopathological grading helps to determine tumor heterogeneity and seek reasons for poor response to therapy. In the light of adding chemotherapy in selected patients with intermediate-grade tumors, the newer scan helps in personalization of the therapy along with the biopsy. The tumor dedifferentiation over the particular time period leading to aggressive behavior, a well-known entity, is contrasted with the redifferentiation phenomenon in some patients as a result of chemotherapy or targeted drug therapy. This may support the basis for combining peptide receptor-targeted radiotherapy/octreotide therapy with chemotherapy or mTOR inhibitors such as everolimus. PMID- 27257870 TI - Usefulness of mean corpuscular volume as a surrogate marker for monitoring thiopurine treatment in inflammatory bowel disease. AB - BACKGROUND: Thiopurines are commonly used drugs in inflammatory bowel disease. Intracellular levels of thiopurine metabolites [i.e. 6-thioguaninenucleotides (6 TGN)] are associated with efficacy and toxicity. Because 6-TGN measurement is not globally available, the mean corpuscular volume (MCV) has been proposed as a surrogate marker for monitoring thiopurine therapy. AIMS: To analyze the relationship between MCV and efficacy of thiopurines, defined as either response to therapy or 6-TGN levels. METHODS: A systematic search on PubMed was performed. RESULTS: Fifteen studies were included. In six studies, a positive association was found between DeltaMCV and 6-TGN. In four studies, it was suggested that DeltaMCV can be used to predict clinical remission. In five articles, no association was found. CONCLUSION: In the majority of articles, it was reported that DeltaMCV is useful in guiding intracellular metabolite levels. However, there is insufficient evidence showing that DeltaMCV can predict clinical remission. PMID- 27257871 TI - Safety of Switching Factor VIII Products in the Era of Evolving Concentrates: Myths and Facts. AB - Recent advances in the development of factor VIII (FVIII) concentrates offer patients with hemophilia the opportunity to switch to products considered safer or with improved properties. In some cases, product switch occurs due to side effects, convenience issues, or economic reasons affecting clinical choices. Reluctance to change FVIII concentrates is shown by patients and also by their physicians, because of concerns in particular about the risk of inhibitor development. A literature review was performed to retrieve the best evidence regarding safety issues of switching FVIII concentrate in patients with severe hemophilia A. Product switch was not associated with an increased inhibitor risk in four studies in patients during the first 50 to 75 exposure days, or in three studies reporting national switches in Canada and United Kingdom. The latter, the only available study comparing switcher and nonswitcher patients, showed an inhibitor incidence similar to that historically reported in the United Kingdom. In 16 phase III clinical trials and 6 postmarketing studies of FVIII concentrates, few de novo inhibitors were detected in previously treated patients, mostly transient and low-titer, with some additional recurrent inhibitors in patients with previous positive testing. On the whole, although rigorous controlled studies are lacking, literature data do not support increased risk of inhibitor development or other safety issues related to product switch. Therefore, in the presence of clinical needs, the advantages of switching FVIII products should not be missed because of perceived more than evidence-based challenges, in particular in this era of products with improved properties recently introduced or available in few years. Caution, however, is suggested in patients with high inhibitor risk, including in those in concomitance with surgery or intensive treatment. A careful inhibitor testing prior to and after product switch is always needed, to identify real de novo inhibitors and to gather further information in the current evolving scenario, in particular comparing switch and nonswitch patients. PMID- 27257872 TI - Correction: Exploring Combinations of Auditory and Visual Stimuli for Gaze Independent Brain-Computer Interfaces. AB - [This corrects the article DOI: 10.1371/journal.pone.0111070.]. PMID- 27257874 TI - Investigated geometrical characteristics and image density of left ventricle of multi-detector computed tomography in early coronary artery disease patients. AB - BACKGROUND: Coronary artery disease (CAD) remains the leading cause of death worldwide. Currently, cardiac multi-detector computed tomography (MDCT) is widely used to diagnose CAD. The purpose in this study is to identify informative and useful predictors from left ventricular (LV) in the early CAD patients using cardiac MDCT images. MATERIALS AND METHODS: Study groups comprised 42 subjects who underwent a screening health examination, including laboratory testing and cardiac angiography by 64-slice MDCT angiography. Two geometrical characteristics and one image density were defined as shape, size and stiffness on MDCT image. The t-test, logistic regression, and receiver operating characteristic curve were applied to assess and identify the significant predictors. The Kappa statistics was used to exam the agreements with physician's judgments (i.e., Golden of True, GOT). RESULTS: The proposed three characteristics of LV MDCT images are important predictors and risk factors for the early CAD patients. These predictors present over 80% of AUC and higher odds ratio. The Kappa statistics was 0.68 for the combinations of shape and stiffness into logistic regression. CONCLUSIONS: The shape, size and stiffness of the left ventricular on MDCT can be used to be the effective indicators in the early CAD patients. Besides, the combinations of shape and stiffness into logistic regression could provide substantial agreement with physician's judgments. PMID- 27257873 TI - Binding of the Fkh1 Forkhead Associated Domain to a Phosphopeptide within the Mph1 DNA Helicase Regulates Mating-Type Switching in Budding Yeast. AB - The Saccharomyces cerevisiae Fkh1 protein has roles in cell-cycle regulated transcription as well as a transcription-independent role in recombination donor preference during mating-type switching. The conserved FHA domain of Fkh1 regulates donor preference by juxtaposing two distant regions on chromosome III to promote their recombination. A model posits that this Fkh1-mediated long-range chromosomal juxtaposition requires an interaction between the FHA domain and a partner protein(s), but to date no relevant partner has been described. In this study, we used structural modeling, 2-hybrid assays, and mutational analyses to show that the predicted phosphothreonine-binding FHA domain of Fkh1 interacted with multiple partner proteins. The Fkh1 FHA domain was important for its role in cell-cycle regulation, but no single interaction partner could account for this role. In contrast, Fkh1's interaction with the Mph1 DNA repair helicase regulated donor preference during mating-type switching. Using 2-hybrid assays, co immunoprecipitation, and fluorescence anisotropy, we mapped a discrete peptide within the regulatory Mph1 C-terminus required for this interaction and identified two threonines that were particularly important. In vitro binding experiments indicated that at least one of these threonines had to be phosphorylated for efficient Fkh1 binding. Substitution of these two threonines with alanines (mph1-2TA) specifically abolished the Fkh1-Mph1 interaction in vivo and altered donor preference during mating-type switching to the same degree as mph1Delta. Notably, the mph1-2TA allele maintained other functions of Mph1 in genome stability. Deletion of a second Fkh1-interacting protein encoded by YMR144W also resulted in a change in Fkh1-FHA-dependent donor preference. We have named this gene FDO1 for Forkhead one interacting protein involved in donor preference. We conclude that a phosphothreonine-mediated protein-protein interface between Fkh1-FHA and Mph1 contributes to a specific long-range chromosomal interaction required for mating-type switching, but that Fkh1-FHA must also interact with several other proteins to achieve full functionality in this process. PMID- 27257875 TI - Dynamic intensity-weighted region of interest imaging for conebeam CT. AB - BACKGROUND: Patient dose from image guidance in radiotherapy is small compared to the treatment dose. However, the imaging beam is untargeted and deposits dose equally in tumor and healthy tissues. It is desirable to minimize imaging dose while maintaining efficacy. OBJECTIVE: Image guidance typically does not require full image quality throughout the patient. Dynamic filtration of the kV beam allows local control of CT image noise for high quality around the target volume and lower quality elsewhere, with substantial dose sparing and reduced scatter fluence on the detector. METHODS: The dynamic Intensity-Weighted Region of Interest (dIWROI) technique spatially varies beam intensity during acquisition with copper filter collimation. Fluence is reduced by 95% under the filters with the aperture conformed dynamically to the ROI during cone-beam CT scanning. Preprocessing to account for physical effects of the collimator before reconstruction is described. RESULTS: Reconstructions show image quality comparable to a standard scan in the ROI, with higher noise and streak artifacts in the outer region but still adequate quality for patient localization. Monte Carlo modeling shows dose reduction by 10-15% in the ROI due to reduced scatter, and up to 75% outside. CONCLUSIONS: The presented technique offers a method to reduce imaging dose by accepting increased image noise outside the ROI, while maintaining full image quality inside the ROI. PMID- 27257877 TI - Sparse sampling in helical cone-beam CT perfect reconstruction algorithms. AB - In the current paper we consider the Helical Cone Beam CT. This scanning method exposes the patient to large quantities of radiation and results in very large amounts of data being collected and stored. Both these facts are prime motivators for the development of an efficient, reduced rate, sampling pattern. We calculate bounds on the support in the frequency domain of the collected data and use these to suggest an efficient sampling pattern. A reduction of up to a factor of 2 in sampling rate is suggested. Indeed, we show that reconstruction quality is not affected by this reduction of sampling rates. PMID- 27257876 TI - Increasing the field of view in grating based X-ray phase contrast imaging using stitched gratings. AB - Grating based X-ray differential phase contrast imaging (DPCI) allows for high contrast imaging of materials with similar absorption characteristics. In the last years' publications, small animals or parts of the human body like breast, hand, joints or blood vessels have been studied. Larger objects could not be investigated due to the restricted field of view limited by the available grating area. In this paper, we report on a new stitching method to increase the grating area significantly: individual gratings are merged on a carrier substrate. Whereas the grating fabrication process is based on the LIGA technology (X-ray lithography and electroplating) different cutting and joining methods have been evaluated. First imaging results using a 2*2 stitched analyzer grating in a Talbot-Lau interferometer have been generated using a conventional polychromatic X-ray source. The image quality and analysis confirm the high potential of the stitching method to increase the field of view considerably. PMID- 27257878 TI - A practical material decomposition method for x-ray dual spectral computed tomography. AB - X-ray dual spectral CT (DSCT) scans the measured object with two different x-ray spectra, and the acquired rawdata can be used to perform the material decomposition of the object. Direct calibration methods allow a faster material decomposition for DSCT and can be separated in two groups: image-based and rawdata-based. The image-based method is an approximative method, and beam hardening artifacts remain in the resulting material-selective images. The rawdata-based method generally obtains better image quality than the image-based method, but this method requires geometrically consistent rawdata. However, today's clinical dual energy CT scanners usually measure different rays for different energy spectra and acquire geometrically inconsistent rawdata sets, and thus cannot meet the requirement. This paper proposes a practical material decomposition method to perform rawdata-based material decomposition in the case of inconsistent measurement. This method first yields the desired consistent rawdata sets from the measured inconsistent rawdata sets, and then employs rawdata-based technique to perform material decomposition and reconstruct material-selective images. The proposed method was evaluated by use of simulated FORBILD thorax phantom rawdata and dental CT rawdata, and simulation results indicate that this method can produce highly quantitative DSCT images in the case of inconsistent DSCT measurements. PMID- 27257880 TI - Analysis of precision in tumor tracking based on optical positioning system during radiotherapy. AB - Tumor tracking is performed during patient set-up and monitoring of respiratory motion in radiotherapy. In the clinical setting, there are several types of equipment for this set-up such as the Electronic Portal imaging Device (EPID) and Cone Beam CT (CBCT). Technically, an optical positioning system tracks the difference between the infra ball reflected from body and machine isocenter. Our objective is to compare the clinical positioning error of patient setup between Cone Beam CT (CBCT) with the Optical Positioning System (OPS), and to evaluate the traditional positioning systems and OPS based on our proposed approach of patient positioning. In our experiments, a phantom was used, and we measured its setup errors in three directions. Specifically, the deviations in the left-to right (LR), anterior-to-posterior (AP) and inferior-to-superior (IS) directions were measured by vernier caliper on a graph paper using the Varian Linear accelerator. Then, we verified the accuracy of OPS based on this experimental study. In order to verify the accuracy of phantom experiment, 40 patients were selected in our radiotherapy experiment. To illustrate the precise of optical positioning system, we designed clinical trials using EPID. From our radiotherapy procedure, we can conclude that OPS has higher precise than conventional positioning methods, and is a comparatively fast and efficient positioning method with respect to the CBCT guidance system. PMID- 27257882 TI - Feature selection of fMRI data based on normalized mutual information and fisher discriminant ratio. AB - Pattern classification has been increasingly used in functional magnetic resonance imaging (fMRI) data analysis. However, the classification performance is restricted by the high dimensional property and noises of the fMRI data. In this paper, a new feature selection method (named as "NMI-F") was proposed by sequentially combining the normalized mutual information (NMI) and fisher discriminant ratio. In NMI-F, the normalized mutual information was firstly used to evaluate the relationships between features, and fisher discriminant ratio was then applied to calculate the importance of each feature involved. Two fMRI datasets (task-related and resting state) were used to test the proposed method. It was found that classification base on the NMI-F method could differentiate the brain cognitive and disease states effectively, and the proposed NMI-F method was prior to the other related methods. The current results also have implications to the future studies. PMID- 27257881 TI - Comparison between Dual Arc VMAT and 7F-IMRT in the protection of hippocampus for patients during whole brain radiotherapy. AB - PURPOSE: The purpose of this study was to compare the dosimetric characteristics for protection of the hippocampus between dual arc VMAT (volumetric modulated arc therapy) and 7 fields intensity-modulated radiation therapy (7F-IMRT) for patients with brain metastases from lung cancer under the whole brain radiotherapy. METHODS: Based on ten cases with brain metastases from lung cancer, two types of radiotherapy plans were designed, namely, dual arc VMAT and 7F-IMRT. Provided that the clinical requirements were satisfied, the comparisons of target dose distribution, conformity index (CI), homogeneity index (HI), dose of organs at risk (OARs), monitor units (MU) and treatment time between dual arc VMAT and 7F-IMRT were investigated for their dosimetric difference. RESULTS: Both treatment plans met the requirements of clinical treatments. However, the PTV-HA conformity and homogeneity of dual arc VMAT were superior to those of 7F-IMRT (P < 0.05). As to OARs, the mean maximum doses (Dmax) of hippocampus, eyes and optic nerves in the dual arc VMAT plan were all lower than those in 7F-IMRT plan (P < 0.05), but the result had no statistical significance (P < 0.05) for the maximum dose of lens. Compared with 7F-IMRT, dual arc VMAT reduced the average number of MU by 67% and the average treatment time by 74%. Therefore, treatment time was shortened by dual arc VMAT. CONCLUSION: With regards to the patients with brain metastases from lung cancer under the whole brain radiotherapy, the PTV-HA conformity and homogeneity of dual arc VMAT were superior to those of 7F-IMRT under the precise of meeting the clinical requirements. In addition, dual arc VMAT remarkably reduced the irradiation dose to OARs (hippocampus, eyes and optic nerves), MU and treatment time, as well, guaranteed patients with better protection. PMID- 27257883 TI - Multi-scale non-local denoising method in neuroimaging. AB - Non-local means algorithm can remove image noise in a unique way that is contrary to traditional techniques. This is because it not only smooths the image but it also preserves the information details of the image. However, this method suffers from high computational complexity. We propose a multi-scale non-local means method in which adaptive multi-scale technique is implemented. In practice, based on each selected scale, the input image is divided into small blocks. Then, we remove the noise in the given pixel by using only one block. This can overcome the low efficiency problem caused by the original non-local means method. Our proposed method also benefits from the local average gradient orientation. In order to perform evaluation, we compared the processed images based on our technique with the ones by the original and the improved non-local means denoising method. Extensive experiments are conducted and results shows that our method is faster than the original and the improved non-local means method. It is also proven that our implemented method is robust enough to remove noise in the application of neuroimaging. PMID- 27257884 TI - Robust kernelized local information fuzzy C-means clustering for brain magnetic resonance image segmentation. AB - Brain tissue segmentation from magnetic resonance (MR) images is an importance task for clinical use. The segmentation process becomes more challenging in the presence of noise, grayscale inhomogeneity, and other image artifacts. In this paper, we propose a robust kernelized local information fuzzy C-means clustering algorithm (RKLIFCM). It incorporates local information into the segmentation process (both grayscale and spatial) for more homogeneous segmentation. In addition, the Gaussian radial basis kernel function is adopted as a distance metric to replace the standard Euclidean distance. The main advantages of the new algorithm are: efficient utilization of local grayscale and spatial information, robustness to noise, ability to preserve image details, free from any parameter initialization, and with high speed as it runs on image histogram. We compared the proposed algorithm with 7 soft clustering algorithms that run on both image histogram and image pixels to segment brain MR images. Experimental results demonstrate that the proposed RKLIFCM algorithm is able to overcome the influence of noise and achieve higher segmentation accuracy with low computational complexity. PMID- 27257885 TI - Activation of Bt Protoxin Cry1Ac in Resistant and Susceptible Cotton Bollworm. AB - Crystalline (Cry) proteins from Bacillus thuringiensis (Bt) are used extensively for insect control in sprays and transgenic plants, but their efficacy is reduced by evolution of resistance in pests. Here we evaluated reduced activation of Cry1Ac protoxin as a potential mechanism of resistance in the invasive pest Helicoverpa armigera. Based on the concentration killing 50% of larvae (LC50) for a laboratory-selected resistant strain (LF120) divided by the LC50 for its susceptible parent strain (LF), the resistance ratio was 1600 for Cry1Ac protoxin and 1200 for trypsin-activated Cry1Ac toxin. The high level of resistance to activated toxin as well as to protoxin indicates reduced activation of protoxin is not a major mechanism of resistance to Cry1Ac in LF120. For both insect strains, treatment with either the trypsin inhibitor N-a-tosyl-L-lysine chloromethyl ketone (TLCK) or the chymotrypsin inhibitor N-a-tosyl-L phenylalanine chloromethyl ketone (TPCK) did not significantly affect the LC50 of Cry1Ac protoxin. Enzyme activity was higher for LF than LF120 for trypsin-like proteases, but did not differ between strains for chymotrypsin-like proteases. The results here are consistent with previous reports indicating that reduced activation of protoxin is generally not a major mechanism of resistance to Bt proteins. PMID- 27257886 TI - Growth and nutrients accumulation potentials of giant reed (Arundo donax L.) in different habitats in Egypt. AB - Arundo donax L. has a high biomass production and a tendency toward community dominance in many habitats and thereby a tolerance to a wide range of environmental conditions. Therefore, the present study investigated the potentiality of A. donax to accumulate nutrients and trace metals in its biomass. Six main habitats (Nile Bank, Drain Bank, Canal Bank, Field Edges, Railways and Roadsides) were recognized. At each habitat, six quadrats (each 1 m(2)), distributed equally in two sites, were selected for growth measurements (e.g., density, shoot height, diameter, leaf area and biomass), plant and soil analyses. Plants from Nile, Canal and Drain Banks had the highest values of most growth measurements, while those from Railways and Roadsides had the lowest. Canal Bank plants accumulated the highest concentrations of P, Cu and Pb in their leaves; Zn in the stem; and Mg, Cd and Fe in the rhizome. The bioaccumulation factor (BF) of A. donax, for Cd, Fe, Mn and Zn, was greater than 1, while the translocation factor (TF) of most trace metals was less than unity in most habitats. In conclusion, A. donax showed morphological plasticity in response to habitat heterogeneity, and its growth was most vigorous in the riparian habitats. The high BF, as well as the significant positive correlations between trace metals, especially Cd, in soil and plant, renders A. donax a powerful phytoremediator. PMID- 27257887 TI - Correction: Psychological Well-Being and the Human Conserved Transcriptional Response to Adversity. AB - [This corrects the article DOI: 10.1371/journal.pone.0121839.]. PMID- 27257888 TI - Altered Decision-Making under Risk in Obesity. AB - BACKGROUND: The negative consequences of energy dense foods are well known, yet people increasingly make unhealthy food choices leading to obesity (i.e., risky decisions). The aims of this study were: [1] to compare performance in decision making tasks under risk and under ambiguity between individuals with obesity, overweight and normal weight; [2] to examine the associations between body mass index (BMI) and decision-making, and the degree to which these associations are modulated by reward sensitivity. METHODS: Seventy-nine adults were recruited and classified in three groups according to their BMI: obesity, overweight and normal weight. Groups were similar in terms of age, education and socio-economic status, and were screened for comorbid medical and mental health conditions. Decision making under risk was measured via the Wheel of Fortune Task (WoFT) and decision making under ambiguity via the Iowa Gambling Task (IGT). Reward sensitivity was indicated by the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ). RESULTS: Individuals with obesity made riskier choices in the WoFT, specifically in choices with an expected value close to zero and in the propensity to risk index. No differences were found in IGT performance or SPSRQ scores. BMI was associated with risk-taking (WoFT performance), independently of reward sensitivity. CONCLUSIONS: Obesity is linked to a propensity to make risky decisions in experimental conditions analogous to everyday food choices. PMID- 27257889 TI - Novel Phospholipid-Protein Conjugates Allow Improved Detection of Antibodies in Patients with Autoimmune Diseases. AB - Reliable measurement of clinically relevant autoimmune antibodies toward phospholipid-protein conjugates is highly desirable in research and clinical assays. To date, the development in this field has been limited to the use of natural heterogeneous antigens. However, this approach does not take structural features of biologically active antigens into account and leads to low reliability and poor scientific test value. Here we describe novel phospholipid protein conjugates for specific detection of human autoimmune antibodies. Our synthetic approach includes mild oxidation of synthetic phospholipid cardiolipin, and as the last step, coupling of the product with azide-containing linker and copper-catalyzed click chemistry with beta2-glycoprotein I and prothrombin. To prove utility of the product antigens, we used enzyme-linked immunosorbent assay and three cohorts of samples obtained from patients in Denmark (n = 34) and the USA (n = 27 and n = 14). Afterwards we analyzed correlation of the obtained autoantibody titers with clinical parameters for each patient. Our results prove that using novel antigens clinically relevant autoantibodies can be detected with high repeatability, sensitivity and specificity. Unlike previously used antigens the obtained autoantibody titers strongly correlate with high disease activity and in particular, with arthritis, renal involvement, anti-Smith antibodies and high lymphocyte count. Importantly, chemical composition of antigens has a strong influence on the correlation of detected autoantibodies with disease activity and manifestations. This confirms the crucial importance of antigens' composition on research and diagnostic assays, and opens up exciting perspectives for synthetic antigens in future studies of autoimmunity. PMID- 27257908 TI - Elastin-Based Rubber-Like Hydrogels. AB - We developed rubber-like elastomeric materials using a natural elastin derived sequence and genetic engineering to create precisely defined elastin-like polypeptides. The coiled elastin-like polypeptide chains, which behave like entropic springs, were cross-linked using an end-to-end tethering scheme to synthesize simple hydrogels with excellent extensibility and reversibility. Our hydrogels extend to strains as high as 1500% and remain highly resilient with elastic recovery as high as 94% even at 600% strain, significantly exceeding any other protein-based hydrogel. These materials are valuable as elastomeric hydrogels for designing extremely robust scaffolds useful for tissue engineering. PMID- 27257910 TI - Minimization of Hypoglycemia as an Adverse Event During Insulin Infusion: Further Refinement of the Yale Protocol. AB - BACKGROUND: The management of hyperglycemia in the intensive care unit has been a controversial topic for more than a decade, with target ranges varying from 80 110 mg/dL to <200 mg/dL. Multiple insulin infusion protocols exist, including several computerized protocols, which have attempted to achieve these targets. Importantly, compliance with these protocols has not been a focus of clinical studies. METHODS: GlucoCareTM, a Food and Drug Administration (FDA)-cleared insulin-dosing calculator, was originally designed based on the Yale Insulin Infusion Protocol to target 100-140 mg/dL and has undergone several modifications to reduce hypoglycemia. The original Yale protocol was modified from 100-140 mg/dL to a range of 120-140 mg/dL (GlucoCare 120-140) and then to 140 mg/dL (GlucoCare 140, not a range but a single blood glucose [BG] level target) in an iterative and evidence-based manner to eliminate hypoglycemia <70 mg/dL. The final modification [GlucoCare 140(B)] includes the addition of bolus insulin "midprotocol" during an insulin infusion to reduce peak insulin rates for insulin resistant patients. This study examined the results of these protocol modifications and evaluated the role of compliance with the protocol in the incidence of hypoglycemia <70 mg/dL. RESULTS: Protocol modifications resulted in mean BG levels of 133.4, 136.4, 143.8, and 146.4 mg/dL and hypoglycemic BG readings <70 mg/dL of 0.998%, 0.367%, 0.256%, and 0.04% for the 100-140, 120-140, 140, and 140(B) protocols, respectively (P < 0.001). Adherence to the glucose check interval significantly reduced the incidence of hypoglycemia (P < 0.001). Protocol modifications led to a reduction in peak insulin infusion rates (P < 0.001) and the need for dextrose-containing boluses (P < 0.001). CONCLUSION: This study demonstrates that refinements in protocol design can improve glucose control in critically ill patients and that the use of GlucoCare 140(B) can eliminate all significant hypoglycemia while achieving mean glucose levels between 140 and 150 mg/dL. In addition, attention to the timely performance of glucose levels can also reduce hypoglycemic events. PMID- 27257909 TI - Anthrax Toxin-Expressing Bacillus cereus Isolated from an Anthrax-Like Eschar. AB - Bacillus cereus isolates have been described harboring Bacillus anthracis toxin genes, most notably B. cereus G9241, and capable of causing severe and fatal pneumonias. This report describes the characterization of a B. cereus isolate, BcFL2013, associated with a naturally occurring cutaneous lesion resembling an anthrax eschar. Similar to G9241, BcFL2013 is positive for the B. anthracis pXO1 toxin genes, has a multi-locus sequence type of 78, and a pagA sequence type of 9. Whole genome sequencing confirms the similarity to G9241. In addition to the chromosome having an average nucleotide identity of 99.98% when compared to G9241, BcFL2013 harbors three plasmids with varying homology to the G9241 plasmids (pBCXO1, pBC210 and pBFH_1). This is also the first report to include serologic testing of patient specimens associated with this type of B. cereus infection which resulted in the detection of anthrax lethal factor toxemia, a quantifiable serum antibody response to protective antigen (PA), and lethal toxin neutralization activity. PMID- 27257911 TI - Rationally Designed 2-in-1 Nanoparticles Can Overcome Adaptive Resistance in Cancer. AB - The development of resistance is the major cause of mortality in cancer. Combination chemotherapy is used clinically to reduce the probability of evolution of resistance. A similar trend toward the use of combinations of drugs is also emerging in the application of cancer nanomedicine. However, should a combination of two drugs be delivered from a single nanoparticle or should they be delivered in two different nanoparticles for maximal efficacy? We explored these questions in the context of adaptive resistance, which emerges as a phenotypic response of cancer cells to chemotherapy. We studied the phenotypic dynamics of breast cancer cells under cytotoxic chemotherapeutic stress and analyzed the data using a phenomenological mathematical model. We demonstrate that cancer cells can develop adaptive resistance by entering into a predetermined transitional trajectory that leads to phenocopies of inherently chemoresistant cancer cells. Disrupting this deterministic program requires a unique combination of inhibitors and cytotoxic agents. Using two such combinations, we demonstrate that a 2-in-1 nanomedicine can induce greater antitumor efficacy by ensuring that the origins of adaptive resistance are terminated by deterministic spatially constrained delivery of both drugs to the target cells. In contrast, a combination of free-form drugs or two nanoparticles, each carrying a single payload, is less effective, arising from a stochastic distribution to cells. These findings suggest that 2-in-1 nanomedicines could emerge as an important strategy for targeting adaptive resistance, resulting in increased antitumor efficacy. PMID- 27257912 TI - Procaine Inhibits Osteo/Odontogenesis through Wnt/beta-Catenin Inactivation. AB - INTRODUCTION: Periodontitis is a complex pathology characterized by the loss of alveolar bone. The causes and the mechanisms that promote this bone resorption still remain unknown. The knowledge of the critical regulators involved in the alteration of alveolar bone homeostasis is of great importance for developing molecular therapies. Procaine is an anesthetic drug with demethylant properties, mainly used by dentists in oral surgeries. The inhibitor role of Wnt signaling of procaine was described in vitro in colon cancer cells. METHODS: In this work we evaluated the role of procaine (1 uM) in osteo/odontogenesis of rat bone marrow mesenchymal stem cells. Similarly, the mechanisms whereby procaine achieves these effects were also studied. RESULTS: Procaine administration led to a drastic decrease of calcium content, alkaline phosphatase activity, alizarin red staining and an increase in the expression of Matrix Gla Protein. With respect to osteo/odontogenic markers, procaine decreased early and mature osteo/odontogenic markers. In parallel, procaine inhibited canonical Wnt/beta-catenin pathway, observing a loss of nuclear beta-catenin, a decrease in Lrp5 and Frizzled 3, a significant increase of sclerostin and Gsk3beta and an increase of phosphorylated beta-catenin. The combination of osteo/odontogenic stimuli and Lithium Chloride decreased mRNA expression of Gsk3beta, recovered by Procaine. Furthermore it was proved that Procaine alone dose dependently increases the expression of Gsk3beta and beta-catenin phosphorylation. These effects of procaine were also observed on mature osteoblast. Interestingly, at this concentration of procaine no demethylant effects were observed. CONCLUSIONS: Our results demonstrated that procaine administration drastically reduced the mineralization and osteo/odontogenesis of bone marrow mesenchymal stem cells inhibiting Wnt/beta catenin pathway through the increase of Gsk3beta expression and beta-catenin phosphorylation. PMID- 27257913 TI - Correction: A Revised Time Tree of the Asterids: Establishing a Temporal Framework For Evolutionary Studies of the Coffee Family (Rubiaceae). AB - [This corrects the article DOI: 10.1371/journal.pone.0126690.]. PMID- 27257914 TI - A Pilot Study Examining Physical and Social Warmth: Higher (Non-Febrile) Oral Temperature Is Associated with Greater Feelings of Social Connection. AB - An emerging literature suggests that experiences of physical warmth contribute to social warmth-the experience of feeling connected to others. Thus, thermoregulatory systems, which help maintain our relatively warm internal body temperatures, may also support feelings of social connection. However, the association between internal body temperature and feelings of connection has not been examined. Furthermore, the origins of the link between physical and social warmth, via learning during early experiences with a caregiver or via innate, co evolved mechanisms, remain unclear. The current study examined the relationship between oral temperature and feelings of social connection as well as whether early caregiver experiences moderated this relationship. Extending the existing literature, higher oral temperature readings were associated with greater feelings of social connection. Moreover, early caregiver experiences did not moderate this association, suggesting that the physical-social warmth overlap may not be altered by early social experience. Results provide additional support for the link between experiences of physical warmth and social warmth and add to existing theories that highlight social connection as a basic need on its own. PMID- 27257915 TI - Multidrug Resistance in Non-PCV13 Serotypes of Streptococcus pneumoniae in Northern Japan, 2014. AB - Since the implementation of routine PCV13 immunization in Japan, nonvaccine serotypes (NVTs) have been increasing among clinical isolates of Streptococcus pneumoniae. In this study, susceptibility to 18 antibiotics was tested for all the 231 isolates with NVTs, which were collected from children <16 years of age in northern Japan in 2014 (July-November). High resistance rates were observed for macrolides (>90.9%), tetracycline (91.3%), and clindamycin (75.3%), while penicillin (PEN) nonsusceptibility (PNSP; MIC >=0.12 MUg/ml) was detected in 42.9% of the pneumococci [39.4%; PEN-intermediate S. pneumoniae (PISP), 3.5%; PEN resistant S. pneumoniae (PRSP)]. All serotype 15A isolates were PRSP (MIC, >=2 MUg/ml) or PISP, and PNSP was prevalent in also serotypes 23A (96.9%), 6C (41%), and 35B (33.3%). Overall, 42.0% of the isolates showed multidrug resistance (MDR). Sequence types (STs) determined for 20 PNSP isolates with NVTs were ST63 (15A), STs 242 or 5832 (6C), STs 338 or 5242 (23A), and ST558 (35B). All the PNSP isolates possessed tet(M), and erm(B) or mefA(A/E), and 70% of them were gPRSP having three altered genes pbp1a, pbp2x, and pbp2b. Among alterations in transpeptidase-coding region of penicillin-binding proteins (PBPs), two substitutions of T371S in the STMK motif and TSQF574-577NTGY in PBP1a were common to all PRSP isolates. The present study showed the spread of PNSP in NVTs 15A, 23A, 6C, and 35B, and the emergence of the MDR international clone Sweden15A-ST63 in northern Japan. PMID- 27257916 TI - Meta-Analysis of the Effect of Bowel Preparation on Adenoma Detection: Early Adenomas Affected Stronger than Advanced Adenomas. AB - BACKGROUND AND AIMS: Low-quality bowel preparation reduces efficacy of colonoscopy. We aimed to summarize effects of bowel preparation on detection of adenomas, advanced adenomas and colorectal cancer. METHODS: A systematic literature search was performed regarding detection of colonic lesions after normal and low-quality bowel preparation. Reported bowel preparation quality was transformed to the Aronchick scale with its qualities "excellent", "good", "fair", "poor", and "insufficient" or "optimal" (good/excellent), "suboptimal" (fair/poor/insufficient), "adequate" (good/excellent/fair) and "inadequate" (poor/insufficient). We identified two types of studies: i) Comparative studies, directly comparing lesion detection according to bowel preparation quality, and ii) repeat colonoscopy studies, reporting results of a second colonoscopy after previous low-quality preparation. RESULTS: The detection of early adenomas was reduced with inadequate vs. adequate bowel preparation (Odds Ratio (OR) 0.53, CI: 0.46-0.62, p<0.001). The advanced adenomas were affected less in comparison (0.74, CI: 0.62-0.87, p<0.001). The large number of subjects considered in the present meta-analysis resulted in smaller confidence intervals compared to earlier studies. Classifying the bowel-preparation quality as suboptimal vs. optimal led to the same qualitative conclusion (OR: 0.81, CI: 0.74-0.89, p<0.001 for early adenomas, OR: 0.94, CI: 0.87-1.01, n.s. for advanced adenomas). Bowel preparation was equally important for right-sided/ flat/ serrated vs. other lesions in most observational studies but more relevant in some repeat colonoscopy studies; data regarding carcinoma detection were insufficient. CONCLUSION: Inadequate bowel preparation affects detection of early colonic lesions stronger than advanced lesions. PMID- 27257917 TI - Quantification and Comparison of Anti-Fibrotic Therapies by Polarized SRM and SHG Based Morphometry in Rat UUO Model. AB - Renal interstitial fibrosis (IF) is an important pathologic manifestation of disease progression in a variety of chronic kidney diseases (CKD). However, the quantitative and reproducible analysis of IF remains a challenge, especially in experimental animal models of progressive IF. In this study, we compare traditional polarized Sirius Red morphometry (SRM) to novel Second Harmonic Generation (SHG)-based morphometry of unstained tissues for quantitative analysis of IF in the rat 5 day unilateral ureteral obstruction (UUO) model. To validate the specificity of SHG for detecting fibrillar collagen components in IF, co localization studies for collagens type I, III, and IV were performed using IHC. In addition, we examined the correlation, dynamic range, sensitivity, and ability of polarized SRM and SHG-based morphometry to detect an anti-fibrotic effect of three different treatment regimens. Comparisons were made across three separate studies in which animals were treated with three mechanistically distinct pharmacologic agents: enalapril (ENA, 15, 30, 60 mg/kg), mycophenolate mofetil (MMF, 2, 20 mg/kg) or the connective tissue growth factor (CTGF) neutralizing antibody, EX75606 (1, 3, 10 mg/kg). Our results demonstrate a strong co localization of the SHG signal with fibrillar collagens I and III but not non fibrillar collagen IV. Quantitative IF, calculated as percent cortical area of fibrosis, demonstrated similar response profile for both polarized SRM and SHG based morphometry. The two methodologies exhibited a strong correlation across all three pharmacology studies (r2 = 0.89-0.96). However, compared with polarized SRM, SHG-based morphometry delivered a greater dynamic range and absolute magnitude of reduction of IF after treatment. In summary, we demonstrate that SHG based morphometry in unstained kidney tissues is comparable to polarized SRM for quantitation of fibrillar collagens, but with an enhanced sensitivity to detect treatment-induced reductions in IF. Thus, performing SHG-based morphometry on unstained kidney tissue is a reliable alternative to traditional polarized SRM for quantitative analysis of IF. PMID- 27257918 TI - sFlt Multivalent Conjugates Inhibit Angiogenesis and Improve Half-Life In Vivo. AB - Current anti-VEGF drugs for patients with diabetic retinopathy suffer from short residence time in the vitreous of the eye. In order to maintain biologically effective doses of drug for inhibiting retinal neovascularization, patients are required to receive regular monthly injections of drug, which often results in low patient compliance and progression of the disease. To improve the intravitreal residence time of anti-VEGF drugs, we have synthesized multivalent bioconjugates of an anti-VEGF protein, soluble fms-like tyrosine kinase-1 (sFlt) that is covalently grafted to chains of hyaluronic acid (HyA), conjugates that are termed mvsFlt. Using a mouse corneal angiogenesis assay, we demonstrate that covalent conjugation to HyA chains does not decrease the bioactivity of sFlt and that mvsFlt is equivalent to sFlt at inhibiting corneal angiogenesis. In a rat vitreous model, we observed that mvsFlt had significantly increased intravitreal residence time compared to the unconjugated sFlt after 2 days. The calculated intravitreal half-lives for sFlt and mvsFlt were 3.3 and 35 hours, respectively. Furthermore, we show that mvsFlt is more effective than the unconjugated form at inhibiting retinal neovascularization in an oxygen-induced retinopathy model, an effect that is most likely due to the longer half-life of mvsFlt in the vitreous. Taken together, our results indicate that conjugation of sFlt to HyA does not affect its affinity for VEGF and this conjugation significantly improves drug half-life. These in vivo results suggest that our strategy of multivalent conjugation could substantially improve upon drug half-life, and thus the efficacy of currently available drugs that are used in diseases such as diabetic retinopathy, thereby improving patient quality of life. PMID- 27257919 TI - Association between Asthma and Autism Spectrum Disorder: A Meta-Analysis. AB - OBJECTIVE: We conducted a meta-analysis to summarize the evidence from epidemiological studies of the association between asthma and autism spectrum disorder (ASD). METHODS: A literature search was conducted using PubMed, Embase, and Cochrane library for studies published before February 2nd, 2016. Observational studies investigating the association between asthma and ASD were included. A random effects model was used to calculate the pooled risk estimates for the outcome. Subgroup analysis was used to explore potential sources of heterogeneity and publication bias was estimated using Begg's and Egger's tests. RESULTS: Ten studies encompassing 175,406 participants and 8,809 cases of ASD were included in this meta-analysis. In the cross-sectional studies, the prevalence of asthma in ASD was 20.4%, while the prevalence of asthma in controls was 15.4% (P < 0.001). The pooled odds ratio (OR) for the prevalence of asthma in ASD in the cross-sectional studies was 1.26 (95% confidence interval (CI): 0.98 1.61) (P = 0.07), with moderate heterogeneity (I2 = 65.0%, P = 0.02) across studies. In the case-control studies, the pooled OR for the prevalence of asthma in ASD was 0.98 (95% CI: 0.68-1.43) (P = 0.94), and there was no evidence of an association between asthma and ASD. No evidence of significant publication bias on the association between asthma and ASD was found. CONCLUSIONS: In conclusion, the results of this meta-analysis do not suggest an association between asthma and ASD. Further prospective studies ascertaining the association between asthma and ASD are warranted. PMID- 27257934 TI - Source Evaluation and Trace Metal Contamination in Benthic Sediments from Equatorial Ecosystems Using Multivariate Statistical Techniques. AB - Trace metals (Cd, Cr, Cu, Ni and Pb) concentrations in benthic sediments were analyzed through multi-step fractionation scheme to assess the levels and sources of contamination in estuarine, riverine and freshwater ecosystems in Niger Delta (Nigeria). The degree of contamination was assessed using the individual contamination factors (ICF) and global contamination factor (GCF). Multivariate statistical approaches including principal component analysis (PCA), cluster analysis and correlation test were employed to evaluate the interrelationships and associated sources of contamination. The spatial distribution of metal concentrations followed the pattern Pb>Cu>Cr>Cd>Ni. Ecological risk index by ICF showed significant potential mobility and bioavailability for Cu, Cu and Ni. The ICF contamination trend in the benthic sediments at all studied sites was Cu>Cr>Ni>Cd>Pb. The principal component and agglomerative clustering analyses indicate that trace metals contamination in the ecosystems was influenced by multiple pollution sources. PMID- 27257935 TI - Iridium Catalysts with f-Amphox Ligands: Asymmetric Hydrogenation of Simple Ketones. AB - A series of modular and rich electronic tridentate ferrocene aminophosphoxazoline ligands (f-amphox) have been successfully developed and used in iridium-catalytic asymmetric hydrogenation of simple ketones to afford corresponding enantiomerically enriched alcohols under mild conditions with superb activities and excellent enantioselectivities (up to 1 000 000 TON, almost all products up to >99% ee, full conversion). The resulting chiral alcohols and their derivatives are important intermediates in pharmaceuticals. PMID- 27257936 TI - Road traffic crashes among farm vehicle drivers in southern China: A cross sectional survey. AB - OBJECTIVE: The objective of this study was to identify the prevalence and potential risk factors of farm vehicle-related road traffic crashes among farm vehicle drivers in southern China. METHODS: A cross-sectional study was used to interview 1,422 farm vehicle drivers in southern China. Farm vehicle-related road traffic crashes that occurred from December 2013 to November 2014 were investigated. Data on farm vehicle-related road traffic crashes and related factors were collected by face-to-face interviews. RESULTS: The prevalence of farm vehicle-related road traffic crashes among the investigated drivers was 7.2%. Farm vehicle-related road traffic crashes were significantly associated with self-reported vision problem (adjusted odds ratio [AOR] = 6.48, 95% confidence interval [CI], 3.86-10.87), self-reported sleep disorders (AOR = 10.03, 95% CI, 6.28-15.99), self-reported stress (AOR = 20.47, 95% CI, 9.96 42.08), reported history of crashes (AOR = 5.40, 95% CI, 3.47-8.42), reported history of drunk driving (AOR = 5.07, 95% CI, 2.97-8.65), and reported history of fatigued driving (AOR = 5.72, 95% CI, 3.73-8.78). The number of road traffic crashes was highest in the daytime and during harvest season. In over 96% of farm vehicle-related road traffic crashes, drivers were believed to be responsible for the crash. Major crash-causing factors included improper driving, careless driving, violating of traffic signals or signs, and being in the wrong lane. CONCLUSION: Findings of this study suggest that farm vehicle-related road traffic crashes have become a burgeoning public health problem in China. Programs need to be developed to prevent farm vehicle-related road traffic crashes in this emerging country. PMID- 27257937 TI - Soft drink wastewater treatment by electrocoagulation-electrooxidation processes. AB - The aim of this work was to implement a coupled system, a monopolar Electrocoagulation (EC)-Electrooxidation (EO) processes, for the treatment of soft drink wastewater. For the EC test, Cu-Cu, anode-cathode were used at current densities of 17, 51 and 68 mA cm-2. Only 37.67% of chemical oxygen demand (COD) and 27% of total organic carbon (TOC) were removed at 20 min with an optimum pH of 8, this low efficiency can be associated with the high concentration of inorganic ions which inhibit the oxidation of organic matter due to their complexation with copper ions. Later EO treatment was performed with boron-doped diamond-Cu electrodes and a current density of 30 Am-2. The coupled EC-EO system was efficient to reduce organic pollutants from initial values of 1875 mg L-1 TOC and 4300 mg L-1 COD, the removal efficiencies were 75% and 85%, respectively. Electric energy consumption to degrade a kilogram of a pollutant in the soft drink wastewater using EC was 3.19 kWh kg-1 TOC and 6.66 kWh kg-1 COD. It was concluded that the coupled system EC-EO was effective for the soft drink wastewater treatment, reducing operating costs and residence time, and allowing its reuse in indirect contact with humans, thus contributing to the sustainable reuse as an effluent of industrial wastewater. PMID- 27257939 TI - New Insights Into the Role of Imidazolium-Based Promoters for the Electroreduction of CO2 on a Silver Electrode. AB - The electrochemical reduction of CO2 to CO is a reaction of central importance for sustainable energy conversion and storage. Herein, structure-activity relationships of a series of imidazolium-based cocatalysts for this reaction are described, which demonstrate that the C4- and C5-protons on the imidazolium ring are vital for efficient catalysis. Further investigation of these findings led to the discovery of new imidazolium salts, which show superior activity as cocatalysts for the reaction, i.e., CO is selectively produced at significantly lower overpotentials with nearly quantitative faradaic yields for CO. PMID- 27257938 TI - Global hypoxia-ischemia induced inflammation and structural changes in the preterm ovine gut which were not ameliorated by mesenchymal stem cell treatment. AB - Perinatal asphyxia, a condition of impaired gas exchange during birth, leads to fetal hypoxia-ischemia (HI) and is associated with postnatal adverse outcomes including intestinal dysmotility and necrotizing enterocolitis (NEC). Evidence from adult animal models of transient, locally-induced intestinal HI has shown that inflammation is essential in HI-induced injury of the gut. Importantly, mesenchymal stem cell (MSC) treatment prevented this HI-induced intestinal damage. We therefore assessed whether fetal global HI induced inflammation, injury and developmental changes in the gut and whether intravenous MSC administration ameliorated these HI-induced adverse intestinal effects. In a preclinical ovine model, fetuses were subjected to umbilical cord occlusion (UCO), with or without MSC treatment, and sacrificed 7 days after UCO. Global HI increased the number of myeloperoxidase positive cells in the mucosa, upregulated mRNA levels of interleukin (IL)-1beta and IL-17 in gut tissue and caused T-cell invasion in the intestinal muscle layer. Intestinal inflammation following global HI was associated with increased Ki67+ cells in the muscularis and subsequent muscle hyperplasia. Global HI caused distortion of glial fibrillary acidic protein immunoreactivity in the enteric glial cells and increased synaptophysin and serotonin expression in the myenteric ganglia. Intravenous MSC treatment did not ameliorate these HI-induced adverse intestinal events. Global HI resulted in intestinal inflammation and enteric nervous system abnormalities which are clinically associated with postnatal complications including feeding intolerance, altered gastrointestinal transit and NEC. The intestinal histopathological changes were not prevented by intravenous MSC treatment directly after HI, indicating that alternative treatment regimens for cell-based therapies should be explored. PMID- 27257940 TI - Development of nanostructures in the diagnosis of drug hypersensitivity reactions. AB - PURPOSE OF REVIEW: This article provides an overview of novel nanoscale structures potentially applicable to the field of allergy, and to discuss the required properties, advantages, and disadvantages of those nanostructures for clinical application focusing on diagnosis of drug hypersensitivity reactions. RECENT FINDINGS: Advances in the development of different nanostructures are favoring their biomedical applications. One area of interest is the interaction between nanostructures and the immune system, including their ability to emulate carrier molecules and their potential use for the diagnosis of allergic reactions. SUMMARY: Immunoassays are the most widely used in-vitro test for evaluating immunoglobulin E (IgE)-mediated drug hypersensitivity reactions. However, they have important technical limitations affecting their sensitivity. A wide variety of nanostructures have been designed to quantify specific IgE, with the aim of diagnosing different kinds of allergies. Nanoparticles-based colloidal immunoassay employed in microdevices and/or miniaturized systems are improving IgE detection sensitivity. Dendrimers have shown immense potential for the design and development of sensor platforms for evaluating IgE-mediated drug hypersensitivity reactions, due to the increase in hapten density and IgE accessibility. In this sense, a variety of dendritic structures as well as their hybridization to different solid supports have been shown to be successful when applied in the diagnosis of drug allergy. Moreover, the knowledge of the complete antigenic determinants would allow their inclusion and therefore further improvement of the sensitivity. PMID- 27257941 TI - The difficult management of anaphylaxis in the elderly. AB - PURPOSE OF REVIEW: In this article, an overview of the main characteristics of the anaphylaxis in the elderly, a subset of the population with particular clinical and physiological features that might influence the presentation and management of this entity, is performed. RECENT FINDINGS: Life expectancy of the population is increasing and so is the prevalence of allergic diseases in the elderly, including anaphylaxis. Older people present higher risk of fatalities after anaphylaxis, and some comorbidities and pharmacological treatments they may use might also increase that risk. SUMMARY: Recognition of the main triggers, the risk factors, and the wide variety of presenting symptoms of anaphylaxis is therefore helpful in its management, as well as a prompt initiation of the treatment and a complete follow-up. PMID- 27257943 TI - The essential tremor syndromes. AB - PURPOSE OF REVIEW: Essential tremor has not been defined or used consistently in clinical diagnosis and research. Other monosymptomatic disorders are often referred to as essential tremor variants. RECENT FINDINGS: There is now solid evidence that essential tremor, however defined, is a syndrome with multiple causes. SUMMARY: A new tremor classification scheme is being developed by the International Parkinson and Movement Disorder Society Task Force on Tremor. In this scheme, tremor in the absence of other neurological signs is called isolated tremor, and tremor in combination with other signs is called combined tremor. Many isolated and combined tremor syndromes can be defined on the basis of commonly recurring or unique clinical symptoms and signs, including historical features (age at onset, family history, and temporal evolution) and tremor characteristics (body distribution, activation condition, associated features). Essential tremor, however defined, is simply a syndrome and not a specific disease. Essential tremor should be defined and used consistently, or this term should be abandoned. As essential tremor is an arbitrarily defined syndrome, it makes no sense to refer to other tremors as variants of essential tremor or essential tremor syndromes. PMID- 27257942 TI - The Relationship between Personality Traits, the 5HTT Polymorphisms, and the Occurrence of Anxiety and Depressive Symptoms in Elite Athletes. AB - The purpose of this study was to determine the relationship between personality, the serotonin transporter (5HTT) polymorphisms and the occurrence of anxiety and depressive symptoms in elite athletes. 133 healthy participants completed the NEO Five-Factor Inventory (NEO-FFI). The mood states were assessed using the Profile of Mood States (POMS) questionnaire. The athlete's mental skills were assessed through the Sport Performance Psychological Inventory (IPPS-48). The occurrence of psychiatric and personality disorders was assessed using the Clinical Interview for DSM-IV Disorders. A polymerase chain reaction was employed to identify genotypes at the 5HTTLPR polymorphism. The 5HTTLPR s/s genotype was associated with both neuroticism (p< 0.001) and tension/anxiety symptoms according to the POMS (p<0.02), cognitive anxiety and emotional arousal control according to the IPPS-48 (p<0.01). Significant correlations were proved between neuroticism and symptoms of anxiety and depression (p<0.05). Neuroticism mediates the association between the 5HTTLPR polymorphism and symptoms of cognitive anxiety and emotional arousal control (p<0.05). These results suggest a significant interaction between the 5HTTLPR polymorphism, neuroticism and sport related stress that predict adverse mental health outcomes in athletes. Identification of homogeneous groups of athletes having predispositions to anxiety and depressive symptoms may help to implement early prevention programs. PMID- 27257946 TI - Tuning noninvasive brain stimulation with MRI to cope with intersubject variability. AB - PURPOSE OF REVIEW: The review aims at highlighting the additional benefit that can be gained from combining noninvasive brain stimulation as well as repetitive sensory stimulation protocols with MRI techniques to account for the intersubject variability observed in those treatments. Potentially, this should help to identify predictive patterns in the individual receptiveness to the treatment. RECENT FINDINGS: Knowledge about the underlying physiological principles of excitability changes as induced by noninvasive brain stimulation or repetitive sensory stimulation is accumulating, revealing strong associations with plasticity processes at the synaptic level. In this context, MRI techniques, such as magnetic resonance spectroscopy and functional MRI, emerged as valuable tools for the qualitative assessment of baseline states and induced changes. Those physiological readouts can help explain the interindividual heterogeneity found in behavioural and/or clinical responses to the specific stimulation protocols. This knowledge will eventually translate, first, into the preliminary classification of study participants into treatment groups according to their neurophysiological baseline state and expected responses to a particular stimulation. Subsequently, this should also aid the optimization of stimulation protocols according to the classification outcome, resulting in retuned protocols for particular groups of study participants. SUMMARY: The consistent MRI-based monitoring of stimulation effects in the neural network promises a considerable gain for the customization of intervention protocols with improved therapeutic potential and rehabilitative predictions. PMID- 27257945 TI - Recent advances in genetics of chorea. AB - PURPOSE OF REVIEW: Chorea presenting in childhood and adulthood encompasses several neurological disorders, both degenerative and nonprogressive, often with a genetic basis. In this review, we discuss how modern genomic technologies are expanding our knowledge of monogenic choreic syndromes and advancing our insight into the molecular mechanisms responsible for chorea. RECENT FINDINGS: A genome wide association study in Huntington's disease identified genetic disease modifiers involved in controlling DNA repair mechanisms and stability of the HTT trinucleotide repeat expansion. Chorea is the cardinal feature of newly recognized genetic entities, ADCY5 and PDE10A-related choreas, with onset in infancy and childhood. A phenotypic overlap between chorea, ataxia, epilepsy, and neurodevelopmental disorders is becoming increasingly evident. SUMMARY: The differential diagnosis of genetic conditions presenting with chorea has considerably widened, permitting a molecular diagnosis and an improved prognostic definition in an expanding number of cases. The identification of Huntington's disease genetic modifiers and new chorea-causing gene mutations has allowed the initial recognition of converging molecular pathways underlying medium spiny neurons degeneration and dysregulation of normal development and activity of basal ganglia circuits. Signalling downstream of dopamine receptors and control of cAMP levels represent a very promising target for the development of new aetiology-based treatments for chorea and other hyperkinetic disorders. PMID- 27257947 TI - BiVO4 -TiO2 Composite Photocatalysts for Dye Degradation Formed Using the SILAR Method. AB - Composite photocatalyst films have been fabricated by depositing BiVO4 upon TiO2 via a sequential ionic layer adsorption reaction (SILAR) method. The photocatalytic materials were investigated by XRD, TEM, UV/Vis diffuse reflectance, inductively coupled plasma optical emission spectrometry (ICP-OES), XPS, photoluminescence and Mott-Schottky analyses. SILAR processing was found to deposit monoclinic-scheelite BiVO4 nanoparticles onto the surface, giving successive improvements in the films' visible light harvesting. Electrochemical and valence band XPS studies revealed that the prepared heterojunctions have a type II band structure, with the BiVO4 conduction band and valence band lying cathodically shifted from those of TiO2 . The photocatalytic activity of the films was measured by the decolourisation of the dye rhodamine 6G using lambda>400 nm visible light. It was found that five SILAR cycles was optimal, with a pseudo-first-order rate constant of 0.004 min(-1) . As a reference material, the same SILAR modification has been made to an inactive wide-band-gap ZrO2 film, where the mismatch of conduction and valence band energies disallows charge separation. The photocatalytic activity of the BiVO4 -ZrO2 system was found to be significantly reduced, highlighting the importance of charge separation across the interface. The mechanism of action of the photocatalysts has also been investigated, in particular the effect of self-sensitisation by the model organic dye and the ability of the dye to inject electrons into the photocatalyst's conduction band. PMID- 27257944 TI - How strong is the evidence that Parkinson's disease is a prion disorder? AB - PURPOSE OF REVIEW: We describe evidence supporting the hypothesis that alpha synuclein has a prion-like role in Parkinson's disease and related alpha synucleinopathies, and discuss how this novel thinking impacts the development of diagnostics and disease-modifying therapies. RECENT FINDINGS: Observations that immature dopamine neurons grafted to Parkinson's disease patients can develop Lewy bodies triggered a surge of interest in the putative prion-like properties of alpha-synuclein. We recount results from experiments which confirm that misfolded alpha-synuclein can exhibit disease-propagating properties, and describe how they relate to the spreading of alpha-synuclein aggregates in alpha synucleinopathies. We share insights into the underlying molecular mechanisms and their relevance to novel therapeutic targets. Finally, we discuss what the initial triggers of alpha-synuclein misfolding might be, where in the body the misfolding events might take place, and how this can instruct development of novel diagnostic tools. We speculate that differences in anatomical trigger sites and variability in alpha-synuclein fibril structure can contribute to clinical differences between alpha-synucleinopathies. SUMMARY: The realization that alpha synuclein pathology can propagate between brain regions in neurodegenerative diseases has deepened and expanded our understanding of potential pathogenic processes which can lead to the development of novel diagnostic tools as well as the identification of new therapeutic targets. PMID- 27257948 TI - Control of Hydroid Colony Form by Surface Heterogeneity. AB - The colonial hydroid Podocoryna carnea grows adherent to surfaces progressing along them by a motile stolon tip. We here ask whether the stolon tip grows preferentially within grooves etched in silicon wafers. In a series of pilot experiments, we varied the dimensions of grooves and found that stolons did not utilize grooves with a width:depth of 5:5 MUm or 10:10 MUm, occasionally followed grooves 25:25 MUm in size, and preferentially grew within grooves of a width:depth of 50:50 MUm and 100:50 MUm. We then grew colonies in grids, with fixed 50:50 MUm width:depth channels intersecting at 90 degrees every 950, 700, 450, or 150 MUm. We find that stolons grew within grooves early in colony ontogeny, but remained restricted to them only in the grid pattern with channel intersections every 150 MUm. Finally, we created a grid in the shape of the Yale Y logo, with channels of 50:50 MUm width:depth and intersections every 100 MUm. The resulting colonies conformed to that of the logo. Our findings demonstrate that stolons respond to surface heterogeneity and that surface etching can be used to fabricate microfluidic circuits comprised of hydroid perisarc. PMID- 27257949 TI - Benefit to Radiation Risk of Breast-specific Gamma Imaging Compared with Mammography in Screening Asymptomatic Women with Dense Breasts. AB - Purpose To estimate the benefit-to-radiation risk ratios of mammography alone, breast-specific gamma imaging (BSGI) alone, and mammography plus BSGI in women with dense breasts who were asymptomatic and examined in the 2015 study by Rhodes et al. Materials and Methods This study uses previously published breast cancer detection rates and estimates of radiation dose and radiation risk and is, therefore, exempt from institutional review board approval. By using breast cancer detection rates for mammography alone, BSGI alone, and mammography plus BSGI from the study by Rhodes et al, as well as lifetime estimates of radiation induced cancer mortality for mammography and BSGI on the basis of the Biologic Effects of Ionizing Radiation VII report, the benefit-to-radiation risk ratios of mammography alone, BSGI alone, and mammography plus BSGI performed annually over 10-year age intervals from ages 40 to 79 years are estimated. Results The benefit to-radiation risk ratio is estimated to be 13 for women who are 40-49 years old and are screened with mammography, a figure that approximately doubles for each subsequent 10-year age interval up to 70-79 years old. For low-dose BSGI, annual screening benefit-to-radiation risk ratios are estimated to be 5 for women 40-49 years old and to double by age 70-79 years, while mammography plus BSGI has benefit-to-radiation risk ratios similar to those of BSGI alone. There are wide ranges for all of these estimates. Conclusion While lower dose (300 MBq) BSGI has estimated benefit-to-radiation risk ratios well in excess of 1 for screening of asymptomatic women with dense breasts who are 40 years old and older, it does not match the benefit-to-radiation risk ratio of screening mammography. (c) RSNA, 2016. PMID- 27257950 TI - Arterial Spin Labeling to Predict Brain Tumor Grading in Children: Correlations between Histopathologic Vascular Density and Perfusion MR Imaging. AB - Purpose To compare arterial spin labeling (ASL) data between low- and high-grade brain tumors in children to establish a cutoff to distinguish low- from high grade neoplasms and to assess potential correlations between cerebral blood flow (CBF) and quantitative histologic microvascular data. Materials and Methods Approval was obtained from the regional review board. ASL data obtained in 129 children between 2011 and 2015 were retrospectively analyzed. CBF and relative CBF in the most perfused area of each neoplasm and contrast enhancement were quantified with a semiquantitative ratio. The correlation between CBF and microvascular density was analyzed in specimens stained with anti-CD34. Results were controlled in two validation cohorts with 1.5- and 3.0-T magnetic resonance (MR) imaging. Results Mean CBF was significantly higher for high-grade than for low-grade hemispheric (116 mL/min/100 g [interquartile range {IQR}, 73-131 mL/min/100 g] vs 29 mL/min/100 g [IQR, 23-35 29 mL/min/100 g], P < .001), thalamic (87 mL/min/100 g [IQR, 73-100 mL/min/100 g] vs 36 mL/min/100 g [IQR, 30 40 mL/min/100 g], P = .016), and posterior fossa (59 mL/min/100 g [IQR, 45-91 mL/min/100 g] vs 33 mL/min/100 g [IQR, 25-40 mL/min/100 g], P < .001) tumors. With a cutoff of 50 mL/min/100 g, sensitivity and specificity were 90% (95% confidence interval [CI]: 68, 100) and 93% (95% CI: 66, 100), respectively, for hemispheric tumors; 100% (95% CI: 48, 100) and 80% (95% CI: 28, 100), respectively, for thalamic tumors; and 65% (95% CI: 51, 78) and 94% (95% CI: 80, 99), respectively, for posterior fossa tumors. In posterior fossa tumors, additional use of the CBF-to-contrast enhancement ratio yielded sensitivity and specificity of 96% (95% CI: 87, 100) and 97% (95% CI: 84, 100), respectively. Use of a simple algorithm based on these values yielded an accuracy of 93% (95% CI: 87, 97). Validation sets yielded similar results, with grading accuracy of 88% (95% CI: 62, 98) with 1.5-T MR imaging and 77% (95% CI: 46, 95) with 3.0-T MR imaging. CBF was strongly correlated with microvascular density (R = 0.66, P < .001). Conclusion High-grade pediatric brain tumors display higher CBF than do low-grade tumors, and they may be accurately graded by using these values. CBF is correlated with tumor microvascular density. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27257951 TI - Effects of Microwave Ablation on Arterial and Venous Vasculature after Treatment of Hepatocellular Carcinoma. AB - Purpose To characterize vessel occlusion rates and their role in local tumor progression in patients with hepatocellular carcinoma (HCC) who underwent microwave tumor ablation. Materials and Methods This institutional review board approved, HIPAA-compliant retrospective review included 95 patients (75 men and 20 women) with 124 primary HCCs who were treated at a single center between January 2011 and March 2014. Complete occlusion of the portal veins, hepatic veins, and hepatic arteries within and directly abutting the ablation zone was identified with postprocedure contrast material-enhanced computed tomography. For each vessel identified in the ablation zone, its size and antenna spacing were recorded and correlated with vascular occlusion with logistic regression analysis. Local tumor progression rates were then compared between patent and occluded vessels for each vessel type with Fisher exact test. Results Occlusion was identified in 39.7% of portal veins (29 of 73), 15.0% of hepatic veins (six of 40), and 14.2% of hepatic arteries (10 of 70) encompassed within the ablation zone. Hepatic vein occlusion was significantly correlated with a smaller vessel size (P = .036) and vessel-antenna spacing (P = .006). Portal vein occlusion was only significantly correlated with a smaller vessel size (P = .001), particularly in vessels that were less than 3 mm in diameter. Local tumor progression rates were significantly correlated with patent hepatic arteries within the ablation zone (P = .02) but not with patent hepatic (P = .57) or portal (P = .14) veins. Conclusion During microwave ablation of HCC, hepatic veins and arteries were resistant to vessel occlusion compared with portal veins, and only arterial patency within an ablation zone was related to local tumor progression. (c) RSNA, 2016. PMID- 27257952 TI - Campylobacter jejuni CsrA Regulates Metabolic and Virulence Associated Proteins and Is Necessary for Mouse Colonization. AB - Campylobacter jejuni infection is a leading bacterial cause of gastroenteritis and a common antecedent leading to Gullian-Barre syndrome. Our previous data suggested that the RNA-binding protein CsrA plays an important role in regulating several important phenotypes including motility, biofilm formation, and oxidative stress resistance. In this study, we compared the proteomes of wild type, csrA mutant, and complemented csrA mutant C. jejuni strains in an effort to elucidate the mechanisms by which CsrA affects virulence phenotypes. The putative CsrA regulon was more pronounced at stationary phase (111 regulated proteins) than at mid-log phase (25 regulated proteins). Proteins displaying altered expression in the csrA mutant included diverse metabolic functions, with roles in amino acid metabolism, TCA cycle, acetate metabolism, and various other cell processes, as well as pathogenesis-associated characteristics such as motility, chemotaxis, oxidative stress resistance, and fibronectin binding. The csrA mutant strain also showed altered autoagglutination kinetics when compared to the wild type. CsrA specifically bound the 5' end of flaA mRNA, and we demonstrated that CsrA is a growth-phase dependent repressor of FlaA expression. Finally, the csrA mutant exhibited reduced ability to colonize in a mouse model when in competition with the wild type, further underscoring the role of CsrA in C. jejuni colonization and pathogenesis. PMID- 27257953 TI - Use of Oxandrolone to Promote Growth in Neonates following Surgery for Complex Congenital Heart Disease: An Open-Label Pilot Trial. AB - OBJECTIVE: Malnutrition and poor weight gain, common in neonates following repair of complex congenital heart disease (CHD), are associated with increased morbidity and mortality. Oxandrolone, an anabolic steroid, improves weight gain in older children at high-risk for growth failure. We sought to determine feasibility, safety, and efficacy of oxandrolone therapy in neonates following surgery for complex CHD. DESIGN: Neonates with RACHS-1 score >3 were eligible to receive open-label oxandrolone for 28 days in this prospective pilot trial. There were 3 cohorts of 5 subjects receiving oxandrolone therapy under 3 specified dosage and preparation protocols: 0.1 mg/kg/day aqueous solution, 0.2 mg/kg/day aqueous solution, and 0.1 mg/kg/day preparation in medium chain triglyceride (MCT) oil. Age- and diagnosis-matched neonates who underwent surgery, but received no oxandrolone, served as a control cohort. Anthropometric measurements, physical examination for virilization, safety labs, and adverse events were monitored. RESULTS: Of 25 eligible patients, 15 consented (60%, 13/15 with Norwood procedure). There was no evidence of virilization, no changes in safety labs, and no serious adverse events related to oxandrolone among subjects receiving therapy. No subject met criteria for termination of study drug. There was a significant difference in change in weight-for-age z-score among the four cohorts, with subjects receiving 0.1 mg/kg/day in MCT oil having the lowest decline during the study period (-1.8 +/- 0.5 for controls, -1.7 +/- 0.4 for 0.1 mg/kg/day aqueous, -1.0 +/- 0.4 for 0.2 mg/kg/day aqueous, and -0.6 +/- 0.7 for 0.1 mg/kg/day MCT oil, P = .012). CONCLUSIONS: Oxandrolone therapy at the doses studied appears safe in neonates after surgery for complex CHD. The decline in weight-for-age z-score was lowest in those receiving the MCT oil preparation suggesting better bioavailability of this preparation and a potential growth benefit with oxandrolone therapy. Further investigation is needed to define optimal dosing and assess efficacy. PMID- 27257954 TI - Laminin Receptor in Shrimp Is a Cellular Attachment Receptor for White Spot Syndrome Virus. AB - White spot syndrome virus (WSSV, genus Whispovirus, family Nimaviridae) is causing huge economic losses in global shrimp farming, but there is no effective control. Shrimp cell laminin receptor (Lamr) may have a role in WSSV infection. The objective was to characterize interactions between Penaeus monodon Lamr (PmLamr) and WSSV structural proteins. In this study, PmLamr interacted with nine WSSV structural proteins (based on yeast two-hybrid screening), of which one (VP31) was characterized. Protein pull-down assay confirmed the interaction between PmLamr and VP31; the latter was an envelope protein exposed outside the WSSV virion (based on membrane topology assays). Furthermore, similar to mammalian Lamr, there were two major protein bands in shrimp cells. Cellular localization assay demonstrated VP31 co-localized with PmLamr on transfected cells. Enzyme-link immunosorbent assay (ELISA) and competitive ELISA demonstrated binding of VP31 on PmLamr was dose-dependent; however, addition of WSSV virion competed for binding affinity. Furthermore, based on an in vivo neutralization assay, both VP31 and PmLamr delayed mortality in shrimp challenged with WSSV. We concluded Lamr was an important receptor for WSSV infection and the viral envelope protein VP31 may have a role in host cell recognition and binding. These data contributed to elucidating pathogenesis of WSSV infection and may help in controlling this disease. PMID- 27257955 TI - Simple and Efficient Ruthenium-Catalyzed Oxidation of Primary Alcohols with Molecular Oxygen. AB - Oxidative transformations utilizing molecular oxygen (O2 ) as the stoichiometric oxidant are of paramount importance in organic synthesis from ecological and economical perspectives. Alcohol oxidation reactions that employ O2 are scarce in homogeneous catalysis and the efficacy of such systems has been constrained by limited substrate scope (most involve secondary alcohol oxidation) or practical factors, such as the need for an excess of base or an additive. Catalytic systems employing O2 as the "primary" oxidant, in the absence of any additive, are rare. A solution to this longstanding issue is offered by the development of an efficient ruthenium-catalyzed oxidation protocol, which enables smooth oxidation of a wide variety of primary, as well as secondary benzylic, allylic, heterocyclic, and aliphatic, alcohols with molecular oxygen as the primary oxidant and without any base or hydrogen- or electron-transfer agents. Most importantly, a high degree of selectivity during alcohol oxidation has been predicted for complex settings. Preliminary mechanistic studies including (18) O labeling established the in situ formation of an oxo-ruthenium intermediate as the active catalytic species in the cycle and involvement of a two-electron hydride transfer in the rate-limiting step. PMID- 27257957 TI - Correction: Taking Perspective: Personal Pronouns Affect Experiential Aspects of Literary Reading. AB - [This corrects the article DOI: 10.1371/journal.pone.0154732.]. PMID- 27257956 TI - Comparative Activity of Ciprofloxacin, Levofloxacin and Moxifloxacin against Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia Assessed by Minimum Inhibitory Concentrations and Time-Kill Studies. AB - The aim of this study was to compare the in vitro susceptibility of Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia to three fluoroquinolones. The minimum inhibitory concentrations (MICs) to ciprofloxacin, levofloxacin and moxifloxacin were examined by E-test(r) for a total of 40 K. pneumoniae strains, 40 S. maltophilia strains and 40 P. aeruginosa strains. Then, the bactericidal activity of these fluoroquinolones was investigated on five strains of each bacterial species by means of time-kill curves. For K. pneumoniae and P. aeruginosa, the distance of the measured MIC from the clinical break-point is a good indicator of the bactericidal activity for ciprofloxacin and levofloxacin as obtained in our experiments. The lower the MIC, the better the bactericidal activity in term of CFU Log decreases. If MIC of ciprofloxacin and levofloxacin against the considered bacteria are far from clinical breakpoint, these two antibiotics are equivalent. According to our MIC50 and modal MIC, the breakpoints of both ciprofloxacin and levofloxacin seem to be somewhat high and data suggest reducing them. On S. maltophilia, none of the tested antibiotics showed a satisfactory activity. PMID- 27257958 TI - Using ventricular modeling to robustly probe significant deep gray matter pathologies: Application to cerebral palsy. AB - Understanding the relationships between the structure and function of the brain largely relies on the qualitative assessment of Magnetic Resonance Images (MRIs) by expert clinicians. Automated analysis systems can support these assessments by providing quantitative measures of brain injury. However, the assessment of deep gray matter structures, which are critical to motor and executive function, remains difficult as a result of large anatomical injuries commonly observed in children with Cerebral Palsy (CP). Hence, this article proposes a robust surrogate marker of the extent of deep gray matter injury based on impingement due to local ventricular enlargement on surrounding anatomy. Local enlargement was computed using a statistical shape model of the lateral ventricles constructed from 44 healthy subjects. Measures of injury on 95 age-matched CP patients were used to train a regression model to predict six clinical measures of function. The robustness of identifying ventricular enlargement was demonstrated by an area under the curve of 0.91 when tested against a dichotomised expert clinical assessment. The measures also showed strong and significant relationships for multiple clinical scores, including: motor function (r2 = 0.62, P < 0.005), executive function (r2 = 0.55, P < 0.005), and communication (r2 = 0.50, P < 0.005), especially compared to using volumes obtained from standard anatomical segmentation approaches. The lack of reliance on accurate anatomical segmentations and its resulting robustness to large anatomical variations is a key feature of the proposed automated approach. This coupled with its strong correlation with clinically meaningful scores, signifies the potential utility to repeatedly assess MRIs for clinicians diagnosing children with CP. Hum Brain Mapp 37:3795-3809, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27257960 TI - A Tunable Silk Hydrogel Device for Studying Limb Regeneration in Adult Xenopus Laevis. AB - In certain amphibian models limb regeneration can be promoted or inhibited by the local wound bed environment. This research introduces a device that can be utilized as an experimental tool to characterize the conditions that promotes limb regeneration in the adult frog (Xenopus laevis) model. In particular, this device was designed to manipulate the local wound environment via a hydrogel insert. Initial characterization of the hydrogel insert revealed that this interaction had a significant influence on mechanical forces to the animal, due to the contraction of the hydrogel. The material and mechanical properties of the hydrogel insert were a factor in the device design in relation to the comfort of the animal and the ability to effectively manipulate the amputation site. The tunable features of the hydrogel were important in determining the pro regenerative effects in limb regeneration, which was measured by cartilage spike formation and quantified by micro-computed tomography. The hydrogel insert was a factor in the observed morphological outcomes following amputation. Future work will focus on characterizing and optimizing the device's observed capability to manipulate biological pathways that are essential for limb regeneration. However, the present work provides a framework for the role of a hydrogel in the device and a path forward for more systematic studies. PMID- 27257959 TI - A Comparative Study of Growth Kinetics, In Vitro Differentiation Potential and Molecular Characterization of Fetal Adnexa Derived Caprine Mesenchymal Stem Cells. AB - The present study was conducted with an objective of isolation, in vitro expansion, growth kinetics, molecular characterization and in vitro differentiation of fetal adnexa derived caprine mesenchymal stem cells. Mid gestation gravid caprine uteri (2-3 months) were collected from abattoir to derive mesenchymal stem cells (MSCs) from fetal adnexa {amniotic fluid (cAF), amniotic sac (cAS), Wharton's jelly (cWJ) and cord blood (cCB)} and expanded in vitro. These cultured MSCs were used at the 3rd passage (P3) to study growth kinetics, localization as well as molecular expression of specific surface antigens, pluripotency markers and mesenchymal tri-lineage differentiation. In comparison to cAF and cAS MSCs, cWJ and cCB MSCs showed significantly (P<0.05) higher clonogenic potency, faster growth rate and low population doubling (PDT) time. All the four types of MSCs were positive for alkaline phosphatase (AP) and differentiated into chondrogenic, osteogenic, and adipogenic lineages. These stem cells expressed MSC surface antigens (CD73, CD90 and CD105) and pluripotency markers (Oct4, Sox2, Nanog, KLF, cMyc, FoxD3) but did not express CD34, a hematopoietic stem cell marker (HSC) as confirmed by RT-PCR, immunocytochemistry and flow cytometric analysis. The relative mRNA expression of MSC surface antigens (CD73, CD90 and CD105) was significantly (P<0.05) higher in cWJ MSCs compared to the other cell lines. The mRNA expression of Oct4 was significantly (P<0.05) higher in cWJ, whereas mRNA expression of KLF and cMyc was significantly (P<0.05) higher in cWJ and cAF than that of cAS and cCB. The comparative assessment revealed that cWJ MSCs outperformed MSCs from other sources of fetal adnexa in terms of growth kinetics, relative mRNA expression of surface antigens, pluripotency markers and tri-lineage differentiation potential, hence, these MSCs could be used as a preferred source for regenerative medicine. PMID- 27257961 TI - Correction: Central Pressure Appraisal: Clinical Validation of a Subject-Specific Mathematical Model. AB - [This corrects the article DOI: 10.1371/journal.pone.0151523.]. PMID- 27257962 TI - Correction: Functional Analysis of Free Fatty Acid Receptor GPR120 in Human Eosinophils: Implications in Metabolic Homeostasis. AB - [This corrects the article DOI: 10.1371/journal.pone.0120386.]. PMID- 27257963 TI - Recurrence of autoimmune liver disease and inflammatory bowel disease after pediatric liver transplantation. AB - Approximately 10% of children with autoimmune hepatitis (AIH) and 30% of those with sclerosing cholangitis (SC) require liver transplantation (LT). LT is indicated in patients who present with fulminant hepatic failure (ie, with encephalopathy) and in those who develop end-stage liver disease despite treatment. After LT, recurrent AIH is reported in approximately 30% of patients and recurrent SC in up to 50%. Diagnosis of recurrence is based on biochemical abnormalities, seropositivity for autoantibodies, interface hepatitis on histology, steroid dependence, and, for SC, presence of cholangiopathy. Recurrence of SC after LT is often associated with poorly controlled inflammatory bowel disease (IBD). Recurrence may even appear years after LT; therefore, steroid-based immunosuppression should be maintained at a higher dose than that used for patients transplanted for nonautoimmune liver diseases. Although the impact of recurrent disease on graft function is controversial, it seems that in pediatric LT recipients recurrence of AIH or SC is associated with compromised graft survival. Exacerbation of preexistent IBD may be observed after LT for SC or AIH, and IBD appears to have a more aggressive course than before LT. In addition, IBD can develop de novo following LT. Liver Transplantation 22 1275 1283 2016 AASLD. PMID- 27257964 TI - Pliable Cognitive MAC for Heterogeneous Adaptive Cognitive Radio Sensor Networks. AB - The rapid expansion of wireless monitoring and surveillance applications in several domains reinforces the trend of exploiting emerging technologies such as the cognitive radio. However, these technologies have to adjust their working concepts to consider the common characteristics of conventional wireless sensor networks (WSNs). The cognitive radio sensor network (CRSN), still an immature technology, has to deal with new networks that might have different types of data, traffic patterns, or quality of service (QoS) requirements. In this paper, we design and model a new cognitive radio-based medium access control (MAC) algorithm dealing with the heterogeneous nature of the developed networks in terms of either the traffic pattern or the required QoS for the node applications. The proposed algorithm decreases the consumed power on several fronts, provides satisfactory levels of latency and spectrum utilization with efficient scheduling, and manages the radio resources for various traffic conditions. An intensive performance evaluation is conducted to study the impact of key parameters such as the channel idle time length, node density, and the number of available channels. The performance evaluation of the proposed algorithm shows a better performance than the comparable protocols. Moreover, the results manifest that the proposed algorithm is suitable for real time monitoring applications. PMID- 27257966 TI - Correction: Caenorhabditis elegans PAQR-2 and IGLR-2 Protect against Glucose Toxicity by Modulating Membrane Lipid Composition. AB - [This corrects the article DOI: 10.1371/journal.pgen.1005982.]. PMID- 27257965 TI - Prevalence and Prognostic Role of BRCA1/2 Variants in Unselected Chinese Breast Cancer Patients. AB - BACKGROUND: The prevalence of BRCA1/2 variants in Chinese breast cancer patients varies among studies. Germline or somatic BRCA1/2 mutations are associated with sensitivity to poly(ADP-ribose) polymerase-1 inhibitors and DNA-damaging agents. We aimed to investigate the distribution of both somatic and germline BRCA1/2 variants in unselected Chinese breast cancer patients, and explore their roles in tumor phenotype and disease prognosis. METHODS: 507 breast cancer patients, unselected for family history of breast cancer or age at diagnosis, were prospectively enrolled from West China Hospital between Feb. 2008 and Feb. 2014. BRCA1/2 variants in the exons/flanking regions were detected in fresh-frozen tumors using next-generation sequencing and confirmed by independent methods. Germline/somatic status was validated by Sanger sequencing in paired blood/normal tissue. RESULTS: BRCA1/2 pathogenic or likely pathogenic (P/LP) variants were detected in 50 patients (9.9%), including 40 germline carriers (18 in BRCA1, 22 in BRCA2), 9 patients with somatic variants (3 in BRCA1, 6 in BRCA2), and 1 patient with concurrent germline/somatic variants in BRCA2. The triple-negative (21.4%) and Luminal B (9.7%) subtypes had higher rates of BRCA1/2 variants. In patients with disease stage 0~II, presence of a germline or somatic BRCA1 P/LP variant increased the risk of relapse as compared to non-carriers [univariate hazard ratio (HR): 3.70, P = 0.04]. Germline BRCA1 P/LP variants, which were associated with aggressive tumor phenotypes, predicted worse disease-free survival in the subgroup of stage 0~II (HR: 4.52, P = 0.02) and N0 (HR: 5.4, P = 0.04) compared to non-carriers. CONCLUSION: A high frequency of germline and somatic BRCA1/2 P/LP variants was detected in unselected Chinese breast cancer patients. Luminal B subtype should be considered as a high-risk population of BRCA1/2 mutation, in addition to triple-negative breast cancer. BRCA1 status was associated with aggressive tumor phenotype and worse disease progression in early stage breast cancer patients. PMID- 27257967 TI - Random Forests for Global and Regional Crop Yield Predictions. AB - Accurate predictions of crop yield are critical for developing effective agricultural and food policies at the regional and global scales. We evaluated a machine-learning method, Random Forests (RF), for its ability to predict crop yield responses to climate and biophysical variables at global and regional scales in wheat, maize, and potato in comparison with multiple linear regressions (MLR) serving as a benchmark. We used crop yield data from various sources and regions for model training and testing: 1) gridded global wheat grain yield, 2) maize grain yield from US counties over thirty years, and 3) potato tuber and maize silage yield from the northeastern seaboard region. RF was found highly capable of predicting crop yields and outperformed MLR benchmarks in all performance statistics that were compared. For example, the root mean square errors (RMSE) ranged between 6 and 14% of the average observed yield with RF models in all test cases whereas these values ranged from 14% to 49% for MLR models. Our results show that RF is an effective and versatile machine-learning method for crop yield predictions at regional and global scales for its high accuracy and precision, ease of use, and utility in data analysis. RF may result in a loss of accuracy when predicting the extreme ends or responses beyond the boundaries of the training data. PMID- 27257968 TI - Development of a large peptoid-DOTA combinatorial library. AB - Conventional one-bead one-compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built-in imaging component for a certain target is a daunting task, and structure-based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule. Such molecules in the library can be used to screen, identify, and validate as direct theranostic candidates against targets of interest. As the first step in achieving that aim, we developed an on-bead library of 153,600 Peptoid-DOTA compounds in which the peptoids are the target-recognizing and potentially therapeutic components and the DOTA is the imaging component. We attached the DOTA scaffold to TentaGel beads using one of the four arms of DOTA, and we built a diversified 6-mer peptoid library on the remaining three arms. We evaluated both the synthesis and the mass spectrometric sequencing capacities of the test compounds and of the final library. The compounds displayed unique ionization patterns including direct breakages of the DOTA scaffold into two units, allowing clear decoding of the sequences. Our approach provides a facile synthesis method for the complete on-bead development of large peptidomimetic DOTA libraries for screening against biological targets for the identification of potential theranostic agents in the future. (c) 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 673-684, 2016. PMID- 27257969 TI - Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV. AB - Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis. PMID- 27257970 TI - Gene Co-Expression Network Analysis for Identifying Modules and Functionally Enriched Pathways in Type 1 Diabetes. AB - Type 1 diabetes (T1D) is a complex disease, caused by the autoimmune destruction of the insulin producing pancreatic beta cells, resulting in the body's inability to produce insulin. While great efforts have been put into understanding the genetic and environmental factors that contribute to the etiology of the disease, the exact molecular mechanisms are still largely unknown. T1D is a heterogeneous disease, and previous research in this field is mainly focused on the analysis of single genes, or using traditional gene expression profiling, which generally does not reveal the functional context of a gene associated with a complex disorder. However, network-based analysis does take into account the interactions between the diabetes specific genes or proteins and contributes to new knowledge about disease modules, which in turn can be used for identification of potential new biomarkers for T1D. In this study, we analyzed public microarray data of T1D patients and healthy controls by applying a systems biology approach that combines network-based Weighted Gene Co-Expression Network Analysis (WGCNA) with functional enrichment analysis. Novel co-expression gene network modules associated with T1D were elucidated, which in turn provided a basis for the identification of potential pathways and biomarker genes that may be involved in development of T1D. PMID- 27257971 TI - Climate-Driven Synchronized Growth of Alpine Trees in the Southeast Tibetan Plateau. AB - Knowledge about the spatiotemporal tree growth variability and its associations with climate provides key insights into forest dynamics under future scenarios of climate change. We synthesized 17 tree-ring width chronologies from four tree species at the high-elevation sites in the southeast Tibetan Plateau (SETP) to study the regional tree growth variability and climate-growth relationships. Despite of diverse habitats and different physiological characteristics of these species, these tree-ring chronologies shared a significant common variance in SETP. An unprecedented increase in the shared variance is found along the latter half of the 20th century, coinciding with the enhancement of the frequency of extreme rings among chronologies. It is found that minimum winter temperature tends to be the dominant climate for trees in this region. The site-specific responses in cold (1965-1980) and warm (1990-2005) intervals by means of Fuzzy Cmeans (FCM) clustering reveal that the remarkable enhancement of growth synchrony among trees mainly occur in warm conditions. This is different from previous findings indicating that increased consistence among temperature sensitive tree rings in cold periods. This may be related to the reduced temperature sensitivity of regional tree growth as winter minimum temperature is lower than a certain threshold, which is in agreement with the "principle of ecological amplitude". In addition, it is worth noting that precipitation in June have started to restrain the tree growth since the beginning of the 1980s, which is possibly an important contributor for synchronized growth among trees in SETP. PMID- 27257972 TI - Epibiotic Diatoms Are Universally Present on All Sea Turtle Species. AB - The macro-epibiotic communities of sea turtles have been subject to growing interest in recent years, yet their micro-epibiotic counterparts are almost entirely unknown. Here, we provide the first evidence that diatoms are epibionts for all seven extant species of sea turtle. Using Scanning Electron Microscopy, we inspected superficial carapace or skin samples from a single representative of each turtle species. We distinguished 18 diatom taxa from these seven individuals, with each sea turtle species hosting at least two diatom taxa. We recommend that future research is undertaken to confirm whether diatom communities vary between sea turtle species and whether these diatom taxa are facultative or obligate commensals. PMID- 27257973 TI - Spontaneous Formation of an Air-Stable Radical upon the Direct Fusion of Diphenylmethane to a Triarylporphyrin. AB - The direct fusion of a diphenylmethane segment to a Ni(II) 5,10,15 triarylporphyrin with three linkages furnished an air- and moisture-stable neutral radical through unexpected and spontaneous oxidation. This radical was demetalated by treatment with H2 SO4 and CF3 CO2 H to provide the corresponding free-base radical. These porphyrin radicals are very stable owing to spin delocalization and have been fully characterized through UV/Vis/NIR absorption spectroscopy, X-ray crystallographic analysis, magnetic susceptibility measurements, electrochemical studies, laser-based ultrafast spectroscopic studies, and theoretical calculations. They were chemically oxidized and reduced to the corresponding cation and anion but did not react with hydrogen-atom donors. PMID- 27257974 TI - Soluble DNAM-1, as a Predictive Biomarker for Acute Graft-Versus-Host Disease. AB - Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera. In retrospective univariate and multivariate analyses of allo-HSCT patients (n = 71) at a single center, cumulative incidences of all grade (grade I-IV) and sgrade II-IV aGVHD in patients with high maximal serum levels of sDNAM-1 (>=30 pM) in the 7 days before allo-HSCT were significantly higher than those in patients with low maximal serum levels of sDNAM-1 (<30 pM) in the same period. However, sDNAM-1 was not associated with other known allo-HSCT complications. Our data suggest that sDNAM-1 is potentially a unique candidate as a predictive biomarker for the development of aGVHD. PMID- 27257976 TI - Gremlin1 expression associates with serrated pathway and favourable prognosis in colorectal cancer. AB - AIMS: Gremlin1 is a bone morphogenetic protein (BMP) antagonist with a suggested role in colorectal cancer (CRC) progression. We have analysed Gremlin1 protein expression in CRC and assessed its correlation with clinicopathological characteristics, including developmental pathway and prognosis. METHODS AND RESULTS: Material included a non-selected series of 148 surgically treated CRC cases. The tumour-node-metastasis (TNM) stage, histological grade and inflammatory infiltrate at the invasive margin were assessed, and tumours were classified to serrated or non-serrated types. Immunohistochemistry was conducted to evaluate Gremlin1 expression. Prognosis (60-month follow-up) was analysed by Kaplan-Meier methods and Cox regression analysis. Gremlin1 expression was detected in epithelial cells both in normal mucosa and in carcinomas. Abundant expression in carcinomas associated with low TNM stage (P = 0.044), low histological grade (P = 0.044), serrated histology (P = 0.033 or P = 0.053 depending on the classification cut-off) and intensive inflammatory infiltrate at the invasive margin (P = 0.044), and was a stage independent indicator of extended survival (P = 0.029). CONCLUSIONS: Gremlin1 protein expression in CRC associates with low tumour stage and extended survival independently of tumour stage, suggesting that it represents a relevant prognostic indicator in CRC. High expression in carcinomas with serrated histology suggests a potential role for Gremlin1 in the serrated pathway of CRC. PMID- 27257977 TI - Effects of Different Ratios of Sewage Sludge and Cattle Manure on Growth and Propagation of Eisenia Fetida. AB - Domestic sewage sludge and cattle manure are rich in nutrition elements, but without proper disposal, are harmful to the environment. Here with an indoor culture method, we used Eisenia fetida to dispose different ratios of sewage sludge and cattle manure, and thereby investigated the effects and acting rules of these sludge-manure mixtures on the growth and reproduction of E. fetida. We find these mixtures are food sources for E. fetida, and their physiochemical properties are significantly changed after disposal by earthworms. Paired samples t-test shows the average change after different treatments is -20.37% for total organic carbon, 85.71% for total Kjeldahl N, -6.67% for total P, 8.33% for pH, 24.78% for EC (ms.cm-1), and -57.10% for C/N ratio. The average growth rate after treatment CD-70 is 9.20 mg.worm-1.day-1; the average growth rates of E. fetida on day 0-28, day 29-56, and day 57-91 are 9.33, 11.90 and 6.95 mg.worm-1.day-1, respectively, indicating a trend of "rapid-rapidest-slow" growth. Other treatments all show this trend. Though all earthworms developed reproductive rings during the test periods, the appearing time and the cocoon production time both differed among these treatments. The cocoon production amount is maximized to 233 after treatment CD-70. The cocoon production rates are significantly different among these treatments, and the maximum and mean are 0.32 and 0.17 0.32, cocoons.worm-1. day-1, respectively. E. fetida can modestly enrich Cd, but is not very effective over Sb or other heavy metals. E. fetida can remove a part of heavy metals from sewage sludge and cattle manure. Generally, the mixtures of sewage sludge and cattle manure can largely affect the growth and propagation of E. fetida in a ratio-dependent way. PMID- 27257979 TI - Evaluation of ceruloplasmin levels in patients with lumbar disc herniation. AB - BACKGROUND: Chronic inflammation is believed to have a role in the development of lumbar disc herniation (LDH). Ceruloplasmin (CP), an acute phase protein, is known to limit inflammation. OBJECTIVE: To evaluate CP levels in patients with LDH. METHODS: Thirty-five patients with LDH and 35 healthy individuals were enrolled in the study. Participants were divided into two groups; group 1 (n = 35) consisted of patients with LDH, and group 2 (n = 35) consisted of healthy subjects. Surgery specimens were taken from all patients who underwent LDH related surgery. CP levels were measured in both blood and tissue samples. Pain intensity was evaluated using a visual analog scale (VAS). RESULTS: There were no significant differences in gender, age, or body mass index between the control and LDH patients (p > 0.05 for all). Compared with the control patients, LDH patients had significantly higher serum CP levels (p < 0.001). In LDH patients, tissue CP levels were significantly higher than serum levels (p < 0.001). According to bivariate analysis, the serum CP levels were significantly correlated with the VAS score in group 1 (r = 0.491, p = 0.003). CONCLUSIONS: The present study showed that CP levels increased in both the serum and the tissues of patients with LDH compared to patients without LDH, possibly as a consequence of LDH-associated inflammation. PMID- 27257978 TI - Safety and Efficacy of Nucleic Acid Polymers in Monotherapy and Combined with Immunotherapy in Treatment-Naive Bangladeshi Patients with HBeAg+ Chronic Hepatitis B Infection. AB - Previous in vivo studies have suggested that nucleic acid polymers (NAPs) may reduce circulating levels of HBsAg in the blood by blocking its release from infected hepatocytes and that this effect may have clinical benefit. NAP treatment, was evaluated in two clinical studies in patients with HBeAg positive chronic HBV infection. The REP 101 study examined REP 2055 monotherapy in 8 patients and the REP 102 study examined REP 2139-Ca, in monotherapy in 12 patients, 9 of which transitioned to short term combined treatment with pegylated interferon alpha 2a or thymosin alpha 1. In both studies NAP monotherapy was accompanied by 2-7 log reductions of serum HBsAg, 3-9 log reductions in serum HBV DNA and the appearance of serum anti-HBsAg antibodies (10-1712 mIU / ml). Eight of the 9 patients transitioning to combined treatment with immunotherapy (pegylated interferon or thymosin alpha 1) in the REP 102 study experienced HBsAg loss and all 9 patients experienced substantial increases in serum anti-HBsAg antibody titers before withdrawal of therapy. For 52 weeks after removal of REP 2055 therapy, rebound of serum viremia (HBV DNA > 1000 copies / ml, HBsAg > 1IU / ml) was not observed in 3 / 8 patients. Suppression of serum virema was further maintained for 290 and 231 weeks in 2 of these patients. After withdrawal of all therapy in the 9 patients that transitioned to combination therapy in the REP 102 study, 8 patients achieved HBV DNA < 116 copies / ml after treatment withdrawal. Viral rebound occurred over a period of 12 to 123 weeks in 7 patients but was still absent in two patients at 135 and 137 weeks of follow-up. Administration tolerability issues observed with REP 2055 were rare with REP 2139-Ca but REP 2139-Ca therapy was accompanied by hair loss, dysphagia and dysgeusia which were considered related to heavy metal exposure endemic at the trial site. These preliminary studies suggest that NAP can elicit important antiviral responses during treatment which may improve the effect of immunotherapy. NAPs may be a potentially useful component of future combination therapies for the treatment of chronic hepatitis B. TRIAL REGISTRATION: ClinicalTrials.gov NCT02646163 and NCT02646189. PMID- 27257975 TI - Skeletal muscle diffusion tensor-MRI fiber tracking: rationale, data acquisition and analysis methods, applications and future directions. AB - The mechanical functions of muscles involve the generation of force and the actuation of movement by shortening or lengthening under load. These functions are influenced, in part, by the internal arrangement of muscle fibers with respect to the muscle's mechanical line of action. This property is known as muscle architecture. In this review, we describe the use of diffusion tensor (DT) MRI muscle fiber tracking for the study of muscle architecture. In the first section, the importance of skeletal muscle architecture to function is discussed. In addition, traditional and complementary methods for the assessment of muscle architecture (brightness-mode ultrasound imaging and cadaver analysis) are presented. Next, DT-MRI is introduced and the structural basis for the reduced and anisotropic diffusion of water in muscle is discussed. The third section discusses issues related to the acquisition of skeletal muscle DT-MRI data and presents recommendations for optimal strategies. The fourth section discusses methods for the pre-processing of DT-MRI data, the available approaches for the calculation of the diffusion tensor and the seeding and propagating of fiber tracts, and the analysis of the tracking results to measure structural properties pertinent to muscle biomechanics. Lastly, examples are presented of how DT-MRI fiber tracking has been used to provide new insights into how muscles function, and important future research directions are highlighted. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27257980 TI - A comparison of the effects of Mulligan's mobilization and Kinesio taping on pain, range of motion, muscle strength, and neck disability in patients with cervical spondylosis: A randomized controlled study1. AB - BACKGROUND: Cervical Spondylosis (CS) is a degenerative and painful pathology, which needs conservative treatment to relieve symptoms. OBJECTIVE: The aim was to investigate the effects of Mulligan's mobilization (MM) and Kinesio taping (KT) on pain, range of motion (ROM), muscle strength, and function in CS. METHODS: Forty-five subjects were randomly placed into three groups: Group 1: control group (conventional rehabilitation-CR); Group 2: MM and CR; Group 3: KT and CR. Assessments including neck pain, cervical ROM, muscle strength and Neck Disability index (NDI) were conducted at baseline, after three-week treatment, and at one-month follow up. Results were analyzed using ANCOVA. RESULTS: In all groups, pain and NDI scores reduced, cervical ROM and muscle strength increased with time (p< 0.001). Greater improvements in neck extension, left and right rotation were obtained in the KT and MM groups when compared to the control group (p< 0.05). In the KT group, improvement in right lateral flexion ROM was greater than the control and deep cervical flexor muscle strength was greater than the MM and the control groups (p< 0.05). CONCLUSION: KT and MM contributed to CR for increasing cervical ROM and deep cervical flexor muscle strength in patients with CS. PMID- 27257981 TI - Single versus multiple dose hyaluronic acid: Comparison of the results. AB - OBJECTIVE: The purpose of this study was to compare the effectiveness of three injections of standard linear HA versus single injection of lightly cross-linking HA in patients with knee OA. METHODS: Forty subjects were randomized into two groups. The first group received single dose intraarticular injection of 4 ml lightly cross-linking sodium hyaluronate (Monovisc), and the second group received three consecutive intraarticular injections of 2.5 ml standard linear sodium hyaluronate (Adant) with one week intervals. Visual analog scale (VAS) pain and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores were measured. RESULTS: In both groups, VAS-pain and WOMAC scores (except WOMAC-stiffness) were improved statistically lasting up to the 6th month with respect to before injection values (p< 0.001). There were no statistical differences in VAS-pain and WOMAC scores after injections (p> 0.05) in both groups. But in the 6th month visit, VAS-resting values were found to be statistically improved in standard linear HA group compared to lightly cross linking HA group (p< 0.05). CONCLUSION: Although three-dose administration was significantly superior to single-dose at the sixth month, current knowledge is not sufficient to decide whether single-dose or multiple-dose HA injection should be chosen. There is a clear need for verification of our results with long-term studies on larger patient groups. PMID- 27257982 TI - Psychological risk factors in back pain patients at an orthopaedic outpatient clinic. AB - BACKGROUND: Psychological risk factors have shown to be important prognostic indicators of back surgery outcome. Prevalence of these risk factors has rarely been examined in an outpatient clinic population. Furthermore, it is unclear to which extent they play a role, in absence of routinely used psychological screening tools, in treatment assignment. OBJECTIVE: First aim of this study was to examine the prevalence of psychological risk factors in back pain patients at an orthopaedic outpatient clinic. Second aim was to investigate the prognostic value of these identified risk factors in treatment assignment by the orthopaedic surgeons (conservative vs. surgery). METHODS: Sixty-six adult back pain patients were included. Psychological risk factor prevalence was determined with the Hospital Anxiety and Depression Scale, Tampa Scale of Kinesiophobia and Pain Catastrophizing Scale. Prognostic value of these risk factors in treatment assignment was examined using statistics. RESULTS: Respectively, 30 (45% HADS Anxiety), 27 (41%, HADS Depression), 19 (29%, PCS) and 37 (56%, TSK) patients scored above cut-off. No prognostic value of risk factors in treatment assignment, was found. CONCLUSIONS: The majority of patients in our study is at risk of poor surgical outcome due to presence of psychological risk factors. Future studies should target the development of screening tools for an early identification of those at risk. PMID- 27257983 TI - Intra-examiner reliability of lumbar spine and neuro-dynamic flexibility measurements in an older and overweight healthy asymptomatic population. AB - BACKGROUND: Measurement of lumbar spine movement and neuro-dynamic flexibility is fundamental to clinical examination and forms part of most systems or protocols used to classify patients with low back pain. However, the increased age and body mass index reported in the chronic low back pain subgroup, may compromise the reliability of these measurements. Specifically, this relates to greater soft tissue excursion relative to the underlying bony landmarks used for these clinical tests. OBJECTIVE: The objective of this research was to determine the intra-examiner reliability for six lumbar spine and two neuro-dynamic examination tests in older and overweight individuals selected to represent a similar age and body mass index of a chronic low back pain population. METHODS: Nineteen volunteers (56.00 +/- 7.62 years) performed sets of eight lumbar spine examination tests. Five repetitions of each set of tests were conducted with rest periods between sets. One examiner measured lumbar flexion, extension, right and left lateral flexion and rotation using a tape measure. A goniometer was used to measure Slump and Passive Straight Leg Raise (PSLR) test. RESULTS: Intra-class correlation coefficients (ICCintra) were calculated to evaluate the reliability of measurement for each test. The eight tests showed ICC ranges between 'Large' and 'Nearly Perfect' (0.68-0.99). Measurement of lateral flexion and rotation had the highest reliability and extension the lowest. CONCLUSIONS: This study was conducted on an asymptomatic older, overweight population and the ICC results support the suitability of these methods and tools for measurement in a clinical setting for this population demographic. Measurement reliability in the study population was comparable with previous research in populations of contrasting demographics. Accordingly, further investigation specifically in a chronic low back pain population is indicated as the paucity of previous literature for some of the movement tests disallowed comparisons, and the reliability reported in this study may not be directly transferable to a chronic low back pain population. PMID- 27257984 TI - Two-Photon Absorption in Conjugated Energetic Molecules. AB - Time-dependent density functional theory (TD-DFT) was used to investigate the relationship between molecular structure and the one- and two-photon absorption (OPA and TPA, respectively) properties of novel and recently synthesized conjugated energetic molecules (CEMs). The molecular structures of CEMs can be strategically altered to influence the heat of formation and oxygen balance, two factors that can contribute to the sensitivity and strength of an explosive material. OPA and TPA are sensitive to changes in molecular structure as well, influencing the optical range of excitation. We found calculated vertical excitation energies to be in good agreement with experiment for most molecules. Peak TPA intensities were found to be significant and on the order of 10(2) GM. Natural transition orbitals for essential electronic states defining TPA peaks of relatively large intensity were used to examine the character of relevant transitions. Modification of molecular substituents, such as additional oxygen or other functional groups, produces significant changes in electronic structure, OPA, and TPA and improves oxygen balance. The results show that certain molecules are apt to undergo nonlinear absorption, opening the possibility for controlled, direct optical initiation of CEMs through photochemical pathways. PMID- 27257985 TI - Lab-on-a-Membrane Foldable Devices for Duplex Drop-Volume Electrochemical Biosensing Using Quantum Dot Tags. AB - This work describes a new type of integrated lab-on-a-membrane foldable device suitable for on-site duplex electrochemical biosensing using drop-size sample volumes. The devices are fabricated entirely by screen-printing on a nylon membrane and feature two assay zones which are located symmetrically on either side of a three-electrode voltammetric cell with a bismuth citrate-loaded graphite working electrode. After the completion of two spatially separated drop volume competitive immunoassays on the assay zones using biotinylated antibodies labeled with streptavidin-conjugated Pb- and Cd-based quantum dots (QDs), respectively, the QD labels are dissolved releasing Pb(II) and Cd(II) in the assay zones. Then, the two assay zones are folded over, and they are brought in contact with the voltammetric cell for simultaneous anodic stripping voltammetric (ASV) determination of Pb(II) and Cd(II) at the bismuth nanostructured layer formed on the working electrode by reduction of the bismuth citrate during the preconcentration step. The fabrication of the devices is discussed in detail, and their operational characteristics are exhaustively studied. In order to demonstrate their applicability to the analysis in complex matrices, duplex ASV QDs-based determination of bovine casein and bovine immunoglobulin G is carried out in milk samples yielding limits of detection of 0.04 MUg mL(-1) and 0.02 MUg mL(-1), respectively. The potential of the devices to detect milk adulteration is further demonstrated. These new membrane devices enable duplex biosensing with distinct advantages over existing approaches in terms of cost, fabrication, and operational simplicity and rapidity, portability, sample size, disposability, sensitivity, and suitability for field analysis. PMID- 27257986 TI - Coreactant Strategy for the Photoredox Catalytic Generation of Trifluoromethyl Radicals under Low-Energy Photoirradiation. AB - Photoredox catalysis has emerged as a valuable alternative to dark-state catalysis. For the full potential of photoredox catalysis to be utilized, it is imperative to make use of low-energy photons in photoinduced radical processes. We have demonstrated that the use of oxalate as a coreactant provides a useful principle for the photocatalytic production of trifluoromethyl radicals (*CF3) from CF3I upon green or red LED photoirradiation of narrow-bandgap photocatalysts. The photocatalytic cycle involves a radical anion of carbon dioxide (CO2(*-)) as a reductant for CF3I, which is generated through photoinduced oxidative decarboxylation of oxalate. Electrochemical characterizations and steady-state and transient photophysical investigations were performed to reveal that there are two photoinduced electron-transfer pathways for oxalate-mediated *CF3 generation. PMID- 27257987 TI - The effects of salinity on the cellular permeability and cytotoxicity of Heterosigma akashiwo. AB - A laboratory study using the fish-killing raphidophyte Heterosigma akashiwo was conducted to examine its capability to grow at salinities below oceanic, and to test the perceived relationship between reduced salinities and increased cytotoxicity. A nonaxenic strain of H. akashiwo isolated from the U.S. Pacific Northwest was exposed to a combination of three salinity (32, 20, and 10) and five temperature (14.7 degrees C, 18.4 degrees C, 21.4 degrees C, 24.4 degrees C and 27.8 degrees C) conditions. Our results demonstrate that cell permeability and cytotoxicity are strongly correlated in unialgal cultures of H. akashiwo, which both increased as salinity decreased from 32 to 10. Furthermore, over a broad median range of salinities (10 and 20), neither temperature nor specific growth rate was correlated with cytotoxicity. However, in cultures grown at the salinity of 32, both temperature and specific growth rate were inversely proportional to toxicity; this relationship was likely due to the effect of contamination by an unidentified species of Skeletonema in those cultures. The presence of Skeletonema sp. resulted in a cytotoxic response from H. akashiwo that was greater than the response caused by salinity alone. These laboratory results reveal the capability of H. akashiwo to become more toxic not only at reduced salinities but also in competition with another algal species. Changes in cell permeability in response to salinity may be an acclimation mechanism by which H. akashiwo is able to respond rapidly to different salinities. Furthermore, due to its strong positive correlation with cytotoxicity, cellular permeability is potentially associated with the ichthyotoxic pathway of this raphytophyte. PMID- 27257988 TI - An 18-year-old man with recurrent pneumothorax since he was 10-year-old. AB - An 18-year-old male patient was referred to the department of pediatric pulmonology with a history of recurrent pneumothorax. Initial pneumothorax occurred at the age of 10. Following diagnosis of congenital lobar emphysema, he had five episodes of pneumothorax and subsequently underwent right-lower lobe anterobasal segmentectomy. Based on thoracic computed tomography (CT) and clinical manifestation, Birt-Hogg-Dube (BHD) syndrome was suspected and confirmed following genetic testing. BHD syndrome is a rare tumor predisposition syndrome first described in 1977. The syndrome is characterized by skin fibrofolliculomas, lung cysts, recurrent spontaneous pneumothorax, and renal cell cancer. The underlying cause is a germline mutation in the folliculin (FLCN) gene located on chromosome 17p11.2. Clinical manifestation usually appears after the age of 20 years. In this case, we report a case of BHD with episodes of recurrent pneumothorax, the first of which occurred at the age of 10 years. Pulmonologists should be aware of this syndrome in patients with a personal and family history of pneumothoraces and CT findings of multiple pulmonary cysts as additional evaluation and testing may be warranted. Pediatr Pulmonol. 2016;51:E41-E43. (c) 2016 Wiley Periodicals, Inc. PMID- 27257989 TI - Association between Interferon Response and Protective Efficacy of NS1-Truncated Mutants as Influenza Vaccine Candidates in Chickens. AB - Influenza virus mutants that encode C-terminally truncated NS1 proteins (NS1 truncated mutants) are attractive candidates for avian live attenuated influenza vaccine (LAIV) development because they are both attenuated and immunogenic in chickens. We previously showed that a high protective efficacy of NS1-truncated LAIV in chickens corresponds with induction of high levels of type I interferon (IFN) responses in chicken embryonic fibroblast cells. In this study, we investigated the relationship between induction of IFN and IFN-stimulated gene responses in vivo and the immunogenicity and protective efficacy of NS1-truncated LAIV. Our data demonstrates that accelerated antibody induction and protective efficacy of NS1-truncated LAIV correlates well with upregulation of IFN stimulated genes. Further, through oral administration of recombinant chicken IFN alpha in drinking water, we provide direct evidence that type I IFN can promote rapid induction of adaptive immune responses and protective efficacy of influenza vaccine in chickens. PMID- 27257990 TI - Evaluation of Health-Related Quality of Life among Tuberculosis Patients in Two Cities in Yemen. AB - BACKGROUND: The health-related quality of life (HRQoL) of Tuberculosis (TB) patients is important because it directly influences the outcome of TB patients in several aspects. The current study aims to evaluate and to find the factors influencing the HRQoL of TB patients in two major TB-prevalent cities (Taiz and Alhodidah) in Yemen. METHODS: A prospective study was conducted, and all TB patients meeting the HRQoL criteria were asked to complete the HRQoL SF-36 survey. The records of TB patients were examined for disease confirmation, and a follow-up was consequently performed for patients during treatment between March 2013 and February 2014 in Taiz and Alhodidah Cities. HRQol scores were calculated by using QM scoring software version 4.5, in which the physical component score (PCS) and mental component score (MCS) were obtained. The scores obtained between 47-53 normal based score (NBS) were considered equivalent to the US normal score. Low scores indicate the poor health situation of TB patients. RESULTS: A total of 243 TB patients enrolled in the study at the beginning of the treatment. A total of 235 and 197 TB patients completed the questionnaire at the end of the intensive phase (I.P.) and continuation phase (C.P.), respectively. The final dropout rate was 16.2%. The mean PCS and MCS scores at the beginning of treatment were low, thus showing the poor health situation of TB patients. The mean PCS scores at the beginning of treatment, end of I.P., and end of treatment were (36.1), (44.9), and (48), respectively. Moreover, the mean MCS score at the beginning of treatment, end of I.P., and end of treatment were (35.1), (42.2), and (44.3), respectively. The result shows that significant increases are observed at the end of I.P. for PCS and MCS because of the treatment and slight changes at the end of C.P. Despite this finding, the MCS score remains below the normal range (47), thus indicating a significant risk of depression among TB patients. Furthermore, general linear repeated measure ANOVA was performed for selected variables, to examine the changes of PCS and MCS over time. It was found that Alhodiah city, chewing khat habit, stigmatization, and duration of treatment more than six months were greatly associated with low mean MCS score of TB patient, indicating great risk of depression which may result in poor treatment outcome. CONCLUSION: TB patients in Yemen were found to have poor QoL, with a significant likelihood of depression. Highly risk depression was found among TB patients in Alhodiah city, khat chewers, stigmatization and having a duration of treatment more than 6 months. Therefore, additional efforts should be made to improve their QoL because it may affect the final clinical outcome of patients. PMID- 27257991 TI - Carbon-Based Adsorbents for Postcombustion CO2 Capture: A Critical Review. AB - The persistent increase in atmospheric CO2 from anthropogenic sources makes research directed toward carbon capture and storage imperative. Current liquid amine absorption technology has several drawbacks including hazardous byproducts and a high-energy requirement for regeneration; therefore, research is ongoing to develop more practical methods for capturing CO2 in postcombustion scenarios. The unique properties of carbon-based materials make them specifically promising for CO2 adsorption at low temperature and moderate to high partial pressure. This critical review aims to highlight the development of carbon-based solid sorbents for postcombustion CO2 capture. Specifically, it provides an overview of postcombustion CO2 capture processes with solid adsorbents and discusses a variety of carbon-based materials that could be used. This review focuses on low cost pyrogenic carbon, activated carbon (AC), and metal-carbon composites for CO2 capture. Further, it touches upon the recent progress made to develop metal organic frameworks (MOFs) and carbon nanomaterials and their general CO2 sorption potential. PMID- 27257992 TI - In Situ Hepatitis C NS3 Protein Detection Is Associated with High Grade Features in Hepatitis C-Associated B-Cell Non-Hodgkin Lymphomas. AB - Hepatitis C Virus (HCV) infection is associated with the B-cell non-Hodgkin lymphomas (NHL), preferentially marginal zone lymphomas (MZL) and diffuse large B cell lymphomas (DLBCL). While chronic antigenic stimulation is a main determinant of lymphomagenesis in marginal zone lymphomas (MZL), a putative role of HCV infection of B-cells is supported by in vitro studies. We performed a pathological study within the "ANRS HC-13 LymphoC" observational study focusing on in situ expression of the oncogenic HCV non structural 3 (NS3) protein. Lympho C study enrolled 116 HCV-positive patients with B-NHL of which 86 histological samples were collected for centralized review. Main histological subtypes were DLBCL (36%) and MZL (34%). Almost half of DLBCL (12/26) were transformed from underlying small B-cell lymphomas. NS3 immunostaining was found positive in 17 of 37 tested samples (46%). There was a striking association between NS3 detection and presence of high grade lymphoma features: 12 out of 14 DLBCL were NS3+ compared to only 4 out of 14 MZL (p = 0.006). Moreover, 2 among the 4 NS3+ MZL were enriched in large cells. Remarkably, this study supports a new mechanism of transformation with a direct oncogenic role of HCV proteins in the occurrence of high-grade B lymphomas. PMID- 27257993 TI - Long-Term Impacts of Foetal Malnutrition Followed by Early Postnatal Obesity on Fat Distribution Pattern and Metabolic Adaptability in Adult Sheep. AB - We aimed to investigate whether over- versus undernutrition in late foetal life combined with obesity development in early postnatal life have differential implications for fat distribution and metabolic adaptability in adulthood. Twin pregnant ewes were fed NORM (100% of daily energy and protein requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein requirements) diets during the last trimester. Postnatally, twin-lambs received obesogenic (HCHF) or moderate (CONV) diets until 6 months of age, and a moderate (obesity correcting) diet thereafter. At 21/2 years of age (adulthood), plasma metabolite profiles during fasting, glucose, insulin and propionate (in fed and fasted states) tolerance tests were examined. Organ weights were determined at autopsy. Early obesity development was associated with lack of expansion of perirenal, but not other adipose tissues from adolescence to adulthood, resulting in 10% unit increased proportion of mesenteric of intra-abdominal fat. Prenatal undernutrition had a similar but much less pronounced effect. Across tolerance tests, LOW-HCHF sheep had highest plasma levels of cholesterol, urea-nitrogen, creatinine, and lactate. Sex specific differences were observed, particularly with respect to fat deposition, but direction of responses to early nutrition impacts were similar. However, prenatal undernutrition induced greater metabolic alterations in adult females than males. Foetal undernutrition, but not overnutrition, predisposed for adult hypercholesterolaemia, hyperureaemia, hypercreatinaemia and hyperlactataemia, which became manifested only in combination with early obesity development. Perirenal expandability may play a special role in this context. Differential nutrition recommendations may be advisable for individuals with low versus high birth weights. PMID- 27257994 TI - Cell wall hydrolases and antibiotics: exploiting synergy to create efficacious new antimicrobial treatments. AB - Cell wall hydrolases (CWH) are enzymes that build, remodel and degrade peptidoglycan within bacterial cell walls and serve essential roles in cell-wall metabolism, bacteriophage adsorption and bacteriolysis, environmental niche expansion, as well as eukaryotic innate immune defense against bacterial infection. Some CWHs, when tested as recombinant purified proteins, have been shown to have bactericidal activities both as single agents and in combinations with other antimicrobials, displaying synergies in vitro and potent activities in animal models of infection greater than the single agents alone. We summarize in vitro, in vivo, and mechanistic studies that illustrate ACWH synergy with antibiotics, antimicrobial peptides, and other ACWHs, underscoring the overall synergistic potential of the ACWH class. PMID- 27257996 TI - Do Paramedics Have a Role to Play in Organ Donation? PMID- 27257997 TI - Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms. AB - Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms. PMID- 27257995 TI - The Emerging Role of Nanotechnology in Cell and Organ Transplantation. AB - Transplantation is often the only choice many patients have when suffering from end-stage organ failure. Although the quality of life improves after transplantation, challenges, such as organ shortages, necessary immunosuppression with associated complications, and chronic graft rejection, limit its wide clinical application. Nanotechnology has emerged in the past 2 decades as a field with the potential to satisfy clinical needs in the area of targeted and sustained drug delivery, noninvasive imaging, and tissue engineering. In this article, we provide an overview of popular nanotechnologies and a summary of the current and potential uses of nanotechnology in cell and organ transplantation. PMID- 27257999 TI - Correction: A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids. AB - [This corrects the article DOI: 10.1371/journal.pone.0154610.]. PMID- 27257998 TI - Similar 5-Year Estimated Glomerular Filtration Rate Between Kidney Transplants From Uncontrolled and Controlled Donors After Circulatory Death-A Dutch Cohort Study. AB - BACKGROUND: Organ shortage persists despite a high rate of donation after circulatory death (DCD) in the Netherlands. The median waiting time for a deceased donor kidney in 2013 was 3.5 years. Most DCD kidneys are from controlled DCD (cDCD; Maastricht category III). Experience with uncontrolled donors after cardiac death (uDCD), that is, donors with an unexpected and irreversible cardiac arrest (Maastricht categories I and II), is increasing; and its effect on transplant outcomes needs evaluation. METHODS: We used the Dutch Organ Transplantation Registry to include recipients (>=18 years old) from all Dutch centers who received transplants from 2002 to 2012 with a first DCD kidney. We compared transplant outcome in uDCD (n = 97) and cDCD (n = 1441). RESULTS: Primary nonfunction in uDCD was higher than in the cDCD (19.6% vs 9.6%, P < 0.001, respectively). Delayed graft function was also higher in uDCD than in cDCD, but not significantly (73.7% vs 63.3%, P = .074, respectively). If censored for primary nonfunction, estimated glomerular filtration rates after 1 year and 5 years were comparable between uDCD and cDCD (1 year: uDCD, 44.3 (23.4) mL/min/m and cDCD, 45.8 (24.1) mL/min/m; P = 0.621; 5 years: uDCD, 49.1 (25.6) mL/min/m and cDCD, 47.7 (21.7) mL/min/m; P = 0.686). The differences in primary nonfunction between kidneys from uDCD and cDCD were explained by differences in the first warm ischemic period, cold ischemic time, and donor age. CONCLUSIONS: We conclude that uDCD kidneys have potential for excellent function and can constitute a valuable extension of the donor pool. However, further efforts are necessary to address the high rate of primary nonfunction. PMID- 27258000 TI - Wavelength Discrimination in Drosophila Suggests a Role of Rhodopsin 1 in Color Vision. AB - Among the five photoreceptor opsins in the eye of Drosophila, Rhodopsin 1 (Rh1) is expressed in the six outer photoreceptors. In a previous study that combined behavioral genetics with computational modeling, we demonstrated that flies can use the signals from Rh1 for color vision. Here, we provide an in-depth computational analysis of wildtype Drosophila wavelength discrimination specifically considering the consequences of different choices of computations in the preprocessing of the behavioral data. The results support the conclusion that Drosophila wavelength discrimination behavior can best be explained by a contribution of Rh1. These findings are corroborated by results of an information theoretical analysis that shows that Rh1 provides information for discrimination of natural reflectance spectra. PMID- 27258001 TI - Correction: Individual Case Analysis of Postmortem Interval Time on Brain Tissue Preservation. AB - [This corrects the article DOI: 10.1371/journal.pone.0151615.]. PMID- 27258002 TI - Family history matters. PMID- 27258003 TI - Differentiation of Murine Bone Marrow-Derived Smooth Muscle Progenitor Cells Is Regulated by PDGF-BB and Collagen. AB - Smooth muscle cells (SMCs) are key regulators of vascular disease and circulating smooth muscle progenitor cells may play important roles in vascular repair or remodelling. We developed enhanced protocols to derive smooth muscle progenitors from murine bone marrow and tested whether factors that are increased in atherosclerotic plaques, namely platelet-derived growth factor-BB (PDGF-BB) and monomeric collagen, can influence the smooth muscle specific differentiation, proliferation, and survival of mouse bone marrow-derived progenitor cells. During a 21 day period of culture, bone marrow cells underwent a marked increase in expression of the SMC markers alpha-SMA (1.93 +/- 0.15 vs. 0.0008 +/- 0.0003 (ng/ng GAPDH) at 0 d), SM22-alpha (1.50 +/- 0.27 vs. 0.005 +/- 0.001 (ng/ng GAPDH) at 0 d) and SM-MHC (0.017 +/- 0.004 vs. 0.001 +/- 0.001 (ng/ng GAPDH) at 0 d). Bromodeoxyuridine (BrdU) incorporation experiments showed that in early culture, the smooth muscle progenitor subpopulation could be identified by high proliferative rates prior to the expression of smooth muscle specific markers. Culture of fresh bone marrow or smooth muscle progenitor cells with PDGF-BB suppressed the expression of alpha-SMA and SM22-alpha, in a rapidly reversible manner requiring PDGF receptor kinase activity. Progenitors cultured on polymerized collagen gels demonstrated expression of SMC markers, rates of proliferation and apoptosis similar to that of cells on tissue culture plastic; in contrast, cells grown on monomeric collagen gels displayed lower SMC marker expression, lower growth rates (319 +/- 36 vs. 635 +/- 97 cells/mm2), and increased apoptosis (5.3 +/- 1.6% vs. 1.0 +/- 0.5% (Annexin 5 staining)). Our data shows that the differentiation and survival of smooth muscle progenitors are critically affected by PDGF-BB and as well as the substrate collagen structure. PMID- 27258004 TI - Plasma C-Reactive Protein and Clinical Outcomes after Acute Ischemic Stroke: A Prospective Observational Study. AB - BACKGROUND AND PURPOSE: Although plasma C-reactive protein (CRP) is elevated in response to inflammation caused by brain infarction, the association of CRP with clinical outcomes after acute ischemic stroke remains uncertain. This study examined whether plasma high-sensitivity CRP (hsCRP) levels at onset were associated with clinical outcomes after acute ischemic stroke independent of conventional risk factors and acute infections after stroke. METHODS: We prospectively included 3653 patients with first-ever ischemic stroke who had been functionally independent and were hospitalized within 24 h of onset. Plasma hsCRP levels were measured on admission and categorized into quartiles. The association between hsCRP levels and clinical outcomes, including neurological improvement, neurological deterioration, and poor functional outcome (modified Rankin scale >=3 at 3 months), were investigated using a logistic regression analysis. RESULTS: Higher hsCRP levels were significantly associated with unfavorable outcomes after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, stroke subtype, conventional risk factors, intravenous thrombolysis and endovascular therapy, and acute infections during hospitalization (multivariate-adjusted odds ratios [95% confidence interval] in the highest quartile versus the lowest quartile as a reference: 0.80 [0.65-0.97] for neurological improvement, 1.72 [1.26-2.34] for neurological deterioration, and 2.03 [1.55-2.67] for a poor functional outcome). These associations were unchanged after excluding patients with infectious diseases occurring during hospitalization, or those with stroke recurrence or death. These trends were similar irrespective of stroke subtypes or baseline stroke severity, but more marked in patients aged <70 years (Pheterogeneity = 0.001). CONCLUSIONS: High plasma hsCRP is independently associated with unfavorable clinical outcomes after acute ischemic stroke. PMID- 27258005 TI - Rhodium-Catalyzed Alkene Difunctionalization with Nitrenes. AB - The Rh(II) -catalyzed oxyamination and diamination of alkenes generate 1,2-amino alcohols and 1,2-diamines, respectively, in good to excellent yields and with complete regiocontrol. In the case of diamination, the intramolecular reaction provides an efficient method for the preparation of pyrrolidines, and the intermolecular reaction produces vicinal amines with orthogonal protecting groups. These alkene difunctionalizations proceed by aziridination followed by nucleophilic ring opening induced by an Rh-bound nitrene generated in situ, details of which were uncovered by both experimental and theoretical studies. In particular, DFT calculations show that the nitrogen atom of the putative [Rh]2 =NR metallanitrene intermediate is electrophilic and support an aziridine activation pathway by N???N=[Rh]2 bond formation, in addition to the N???[Rh]2 =NR coordination mode. PMID- 27258006 TI - Oxidative stress response induced in an atrazine phytoremediating plant: physiological responses of Pennisetum glaucum to high atrazine concentrations. AB - This research presented here, for the first time, elucidates the responses of several antioxidants in Pennisetum leaves exposed to varying concentrations of atrazine (0 - 200 mg*kg-1). Pennisetum has been reported to be resistant to atrazine; however, its physiological response to high concentrations (>= 50 mg*kg 1) of atrazine is not well documented. The contents of reduced (AsA) and oxidized (DHA) ascorbate increased significantly with increase in atrazine concentration and exposure time; but the increase was more evident under higher (50 and 100 mg*kg-1) atrazine concentrations. Increase in atrazine concentration to 200 mg*kg 1 significantly decreased AsA, but increased DHA content, throughout the experiment. Seedlings treated with 200 mg*kg-1 atrazine showed significantly lowest reduced glutathione (GSH) content; while oxidized glutathione (GSSG) was not significantly affected, after 68d. Seedlings treated with 100 mg*kg-1 atrazine showed increased Glutathione-S-Transferase (GST) activity after 48 d and 68 d; while treatment with 200 mg*kg-1 atrazine significantly increased Glutathione reductase (GR) after 58d. This result suggests that Pennisetum may tolerate lower atrazine concentrations; However, higher concentrations (>=50 mg*kg-1) which could have longer residency period in the soil, could induce more physiological damage to the plant. PMID- 27258007 TI - Social Network Analysis and Qualitative Interviews for Assessing Geographic Characteristics of Tourism Business Networks. AB - This study integrates quantitative social network analysis (SNA) and qualitative interviews for understanding tourism business links in isolated communities through analysing spatial characteristics. Two case studies are used, the Surselva-Gotthard region in the Swiss Alps and Longyearbyen in the Arctic archipelago of Svalbard, to test the spatial characteristics of physical proximity, isolation, and smallness for understanding tourism business links. In the larger Surselva-Gotthard region, we found a strong relationship between geographic separation of the three communities on compartmentalization of the collaboration network. A small set of businesses played a central role in steering collaborative decisions for this community, while a group of structurally 'peripheral' actors were less influential. By contrast, the business community in Svalbard showed compartmentalization that was independent of geographic distance between actors. Within towns of similar size and governance scale, Svalbard is more compartmentalized, and those compartments are not driven by geographic separation of the collaboration clusters. This compartmentalization in Svalbard was reflected in a lower density of formal business collaboration ties compared to the communities of the Alps. We infer that the difference is due to Svalbard having higher cultural diversity and population turnover than the Alps communities. We propose that integrating quantitative network analysis from simple surveys with qualitative interviews targeted from the network results is an efficient general approach to identify regionally specific constraints and opportunities for effective governance. PMID- 27258008 TI - Leukocyte-Rich Platelet-Rich Plasma Injections Do Not Up-Modulate Intra-Articular Pro-Inflammatory Cytokines in the Osteoarthritic Knee. AB - INTRODUCTION: The presence of leukocytes in platelet concentrates is deemed to cause deleterious effects when injected intra articularly. The aim of this study is to analyse both local and systemic effects induced by leukocyte-rich Platelet rich Plasma (PRP) injections through a proteomic characterization of serial synovial fluid and blood samples obtained from subjects treated for knee OA. Secondary aim was to compare the effects on knee homeostasis and systemic response with those obtained with visco-supplementation. METHODS: Thirty-six OA patients treated either by autologous L-PRP or HA intra-articular knee injections, administered in series of three at one-week intervals, were analyzed. Just before the injection, 1 ml of synovial fluid was collected through the same needle way. In the same time, a peripheral blood sample was obtained and plasma separated. A further peripheral blood sample was collected at 2, 6, and 12 months. L-PRP, plasma and synovial fluid were tested by multiplex bead-based sandwich immunoassay by means of the Bio-Plex suspension array system (Bio-Rad Laboratories) for the presence of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-17 and IL-4, IL-10, IL-13) and growth factors (FGF-b, HGF, PDGF AB/BB). RESULTS: In general, pro-inflammatory cytokine levels were similar at basal condition and after treatment whereas anti-inflammatory ones were nearly undetectable. L-PRP administration did not modulate significant changes of cytokine concentrations either in synovial fluid or plasma, whatever the time points analyzed. No different trend was observed between L-PRP and HA administration in terms of pro- and anti-inflammatory cytokines, as well as growth factors. CONCLUSIONS: In contrast with the evidence reported by "in vitro" studies, where a cellular pro-inflammatory response appears to be induced by the presence of leukocytes, these results suggest that the presence leukocyte-rich PRP doesn't induce a relevant in vivo up regulation of pro-inflammatory mediators. PMID- 27258010 TI - The Creation of Surrogate Models for Fast Estimation of Complex Model Outcomes. AB - A surrogate model is a black box model that reproduces the output of another more complex model at a single time point. This is to be distinguished from the method of surrogate data, used in time series. The purpose of a surrogate is to reduce the time necessary for a computation at the cost of rigor and generality. We describe a method of constructing surrogates in the form of support vector machine (SVM) regressions for the purpose of exploring the parameter space of physiological models. Our focus is on the methodology of surrogate creation and accuracy assessment in comparison to the original model. This is done in the context of a simulation of hemorrhage in one model, "Small", and renal denervation in another, HumMod. In both cases, the surrogate predicts the drop in mean arterial pressure following the intervention. We asked three questions concerning surrogate models: (1) how many training examples are necessary to obtain an accurate surrogate, (2) is surrogate accuracy homogeneous, and (3) how much can computation time be reduced when using a surrogate. We found the minimum training set size that would guarantee maximal accuracy was widely variable, but could be algorithmically generated. The average error for the pressure response to the protocols was -0.05+/-2.47 in Small, and -0.3 +/- 3.94 mmHg in HumMod. In the Small model, error grew with actual pressure drop, and in HumMod, larger pressure drops were overestimated by the surrogates. Surrogate use resulted in a 6 order of magnitude decrease in computation time. These results suggest surrogate modeling is a valuable tool for generating predictions of an integrative model's behavior on densely sampled subsets of its parameter space. PMID- 27258009 TI - Novel Plasminogen Activator Inhibitor-1 Inhibitors Prevent Diabetic Kidney Injury in a Mouse Model. AB - Diabetic nephropathy is the leading cause of end-stage renal disease worldwide, but no effective therapeutic strategy is available. Because plasminogen activator inhibitor-1 (PAI-1) is increasingly recognized as a key factor in extracellular matrix (ECM) accumulation in diabetic nephropathy, this study examined the renoprotective effects of TM5275 and TM5441, two novel orally active PAI-1 inhibitors that do not trigger bleeding episodes, in streptozotocin (STZ)-induced diabetic mice. TM5275 (50 mg/kg) and TM5441 (10 mg/kg) were administered orally for 16 weeks to STZ-induced diabetic and age-matched control mice. Relative to the control mice, the diabetic mice showed significantly increased (p < 0.05) plasma glucose and creatinine levels, urinary albumin excretion, kidney-to bodyweight ratios, glomerular volume, and fractional mesangial area. Markers of fibrosis and inflammation along with PAI-1 were also upregulated in the kidney of diabetic mice, and treatment with TM5275 and TM5441 effectively inhibited albuminuria, mesangial expansion, ECM accumulation, and macrophage infiltration in diabetic kidneys. Furthermore, in mouse proximal tubular epithelial (mProx24) cells, both TM5275 and TM5441 effectively inhibited PAI-1-induced mRNA expression of fibrosis and inflammation markers and also reversed PAI-1-induced inhibition of plasmin activity, which confirmed the efficacy of the TM compounds as PAI-1 inhibitors. These data suggest that TM compounds could be used to prevent diabetic kidney injury. PMID- 27258011 TI - Response of a Habitat-Forming Marine Plant to a Simulated Warming Event Is Delayed, Genotype Specific, and Varies with Phenology. AB - Growing evidence shows that increasing global temperature causes population declines and latitudinal shifts in geographical distribution for plants living near their thermal limits. Yet, even populations living well within established thermal limits of a species may suffer as the frequency and intensity of warming events increase with climate change. Adaptive response to this stress at the population level depends on the presence of genetic variation in thermal tolerance in the populations in question, yet few data exist to evaluate this. In this study, we examined the immediate effects of a moderate warming event of 4.5 degrees C lasting 5 weeks and the legacy effects after a 5 week recovery on different genotypes of the marine plant Zostera marina (eelgrass). We conducted the experiment in Bodega Bay, CA USA, where average summer water temperatures are 14-15 degrees C, but extended warming periods of 17-18 degrees C occur episodically. Experimental warming increased shoot production by 14% compared to controls held at ambient temperature. However, after returning temperature to ambient levels, we found strongly negative, delayed effects of warming on production: shoot production declined by 27% and total biomass decreased by 50% relative to individuals that had not been warmed. While all genotypes' production decreased in the recovery phase, genotypes that grew the most rapidly under benign thermal conditions (control) were the most susceptible to the detrimental effects of warming. This suggests a potential tradeoff in relative performance at normal vs. elevated temperatures. Modest short-term increases in water temperature have potentially prolonged negative effects within the species' thermal envelope, but genetic variation within these populations may allow for population persistence and adaptation. Further, intraspecific variation in phenology can result in maintenance of population diversity and lead to enhanced production in diverse stands given sufficient frequency of warming or other stress events. PMID- 27258012 TI - Reflections on the Unintended Consequences of the Promotion of Institutional Pregnancy and Birth Care in Burkina Faso. AB - The policy of institutional delivery has been the cornerstone of actions aimed at monitoring and achieving MDG 5. Efforts to increase institutional births have been implemented worldwide within different cultural and health systems settings. This paper explores how communities in rural Burkina Faso perceive the promotion and delivery of facility pregnancy and birth care, and how this promotion influences health-seeking behaviour. A qualitative study was conducted in South Western Burkina Faso between September 2011 and January 2012. A total of 21 in depth interviews and 8 focus group discussions with women who had given birth recently and community members were conducted. The data were analyzed using qualitative content analysis and interpreted through Merton's concept of unintended consequences of purposive social action. The study found that community members experienced a strong pressure to give birth in a health facility and perceived health workers to define institutional birth as the only acceptable option. Women and their families experienced verbal, economic and administrative sanctions if they did not attend services and adhered to health worker recommendations, and reported that they felt incapable of questioning health workers' knowledge and practices. Women who for social and economic reasons had limited access to health facilities found that the sanctions came with increased cost for health services, led to social stigma and acted as additional barriers to seek skilled care at birth. The study demonstrates how the global and national policy of skilled pregnancy and birth care can occur in unintentional ways in local settings. The promotion of institutional care during pregnancy and at birth in the study area compromised health system trust and equal access to care. The pressure to use facility care and the sanctions experienced by women not complying may further marginalize women with poor access to facility care and contribute to worsened health outcomes. PMID- 27258013 TI - Receiver-Based Ad Hoc On Demand Multipath Routing Protocol for Mobile Ad Hoc Networks. AB - Decreasing the route rediscovery time process in reactive routing protocols is challenging in mobile ad hoc networks. Links between nodes are continuously established and broken because of the characteristics of the network. Finding multiple routes to increase the reliability is also important but requires a fast update, especially in high traffic load and high mobility where paths can be broken as well. The sender node keeps re-establishing path discovery to find new paths, which makes for long time delay. In this paper we propose an improved multipath routing protocol, called Receiver-based ad hoc on demand multipath routing protocol (RB-AOMDV), which takes advantage of the reliability of the state of the art ad hoc on demand multipath distance vector (AOMDV) protocol with less re-established discovery time. The receiver node assumes the role of discovering paths when finding data packets that have not been received after a period of time. Simulation results show the delay and delivery ratio performances are improved compared with AOMDV. PMID- 27258014 TI - Strong, but Wrong: Lay People's and Police Officers' Beliefs about Verbal and Nonverbal Cues to Deception. AB - The present study investigated the beliefs of students and police officers about cues to deception. A total of 95 police officers and 104 undergraduate students filled out a questionnaire addressing beliefs about cues to deception. Twenty eight verbal cues were included in the questionnaire, all extracted from verbal credibility assessment tools (i.e., CBCA, RM, and SCAN). We investigated to what extent beliefs about nonverbal and verbal cues of deception differed between lay people (students) and police officers, and whether these beliefs were in agreement with objective cues known from research. Both students and police officers believed the usual stereotypical, but non-diagnostic (nonverbal) cues such as gaze aversion and increased movement to be indicative of deception. Yet, participants were less inclined to overestimate the relationship between verbal cues and deception and their beliefs fitted better with what we know from research. The implications of these findings for practice are discussed. PMID- 27258016 TI - For the love of it: Affective experiences that may increase physical activity participation among older adults. PMID- 27258015 TI - Membrane Transfer from Mononuclear Cells to Polymorphonuclear Neutrophils Transduces Cell Survival and Activation Signals in the Recipient Cells via Anti Extrinsic Apoptotic and MAP Kinase Signaling Pathways. AB - The biological significance of membrane transfer (trogocytosis) between polymorphonuclear neutrophils (PMNs) and mononuclear cells (MNCs) remains unclear. We investigated the biological/immunological effects and molecular basis of trogocytosis among various immune cells in healthy individuals and patients with active systemic lupus erythematosus (SLE). By flow cytometry, we determined that molecules in the immunological synapse, including HLA class-I and-II, CD11b and LFA-1, along with CXCR1, are exchanged among autologous PMNs, CD4+ T cells, and U937 cells (monocytes) after cell-cell contact. Small interfering RNA knockdown of the integrin adhesion molecule CD11a in U937 unexpectedly enhanced the level of total membrane transfer from U937 to PMN cells. Functionally, phagocytosis and IL-8 production by PMNs were enhanced after co-culture with T cells. Total membrane transfer from CD4+ T to PMNs delayed PMN apoptosis by suppressing the extrinsic apoptotic molecules, BAX, MYC and caspase 8. This enhancement of activities of PMNs by T cells was found to be mediated via p38- and P44/42-Akt-MAP kinase pathways and inhibited by the actin-polymerization inhibitor, latrunculin B, the clathrin inhibitor, Pitstop-2, and human immunoglobulin G, but not by the caveolin inhibitor, methyl-beta-cyclodextrin. In addition, membrane transfer from PMNs enhanced IL-2 production by recipient anti CD3/anti-CD28 activated MNCs, and this was suppressed by inhibitors of mitogen activated protein kinase (PD98059) and protein kinase C (Rottlerin). Of clinical significance, decreased total membrane transfer from PMNs to MNCs in patients with active SLE suppressed mononuclear IL-2 production. In conclusion, membrane transfer from MNCs to PMNs, mainly at the immunological synapse, transduces survival and activation signals to enhance PMN functions and is dependent on actin polymerization, clathrin activation, and Fcgamma receptors, while membrane transfer from PMNs to MNCs depends on MAP kinase and PKC signaling. Defective membrane transfer from PMNs to MNCs in patients with active systemic lupus erythematous suppressed activated mononuclear IL-2 production. PMID- 27258017 TI - The influence of patients' immigration background and residence permit status on treatment decisions in health care. Results of a factorial survey among general practitioners in Switzerland. AB - This study examines the influence of patients' immigration background and residence permit status on physicians' willingness to treat patients in due time. A factorial survey was conducted among 352 general practitioners with a background in internal medicine in a German-speaking region in Switzerland. Participants expressed their self-rating (SR) as well as the expected colleague rating (CR) to provide immediate treatment to 12 fictive vignette patients. The effects of the vignette variables were analysed using random-effects models. The results show that SR as well as CR was not only influenced by the medical condition or the physicians' time pressure, but also by social factors such as the ethnicity and migration history, the residence permit status, and the economic condition of the patients. Our findings can be useful for the development of adequate, practically relevant teaching and training materials with the ultimate aim to reduce unjustified discrimination or social rationing in health care. PMID- 27258018 TI - Tremor Detection Using Parametric and Non-Parametric Spectral Estimation Methods: A Comparison with Clinical Assessment. AB - In the clinic, tremor is diagnosed during a time-limited process in which patients are observed and the characteristics of tremor are visually assessed. For some tremor disorders, a more detailed analysis of these characteristics is needed. Accelerometry and electromyography can be used to obtain a better insight into tremor. Typically, routine clinical assessment of accelerometry and electromyography data involves visual inspection by clinicians and occasionally computational analysis to obtain objective characteristics of tremor. However, for some tremor disorders these characteristics may be different during daily activity. This variability in presentation between the clinic and daily life makes a differential diagnosis more difficult. A long-term recording of tremor by accelerometry and/or electromyography in the home environment could help to give a better insight into the tremor disorder. However, an evaluation of such recordings using routine clinical standards would take too much time. We evaluated a range of techniques that automatically detect tremor segments in accelerometer data, as accelerometer data is more easily obtained in the home environment than electromyography data. Time can be saved if clinicians only have to evaluate the tremor characteristics of segments that have been automatically detected in longer daily activity recordings. We tested four non-parametric methods and five parametric methods on clinical accelerometer data from 14 patients with different tremor disorders. The consensus between two clinicians regarding the presence or absence of tremor on 3943 segments of accelerometer data was employed as reference. The nine methods were tested against this reference to identify their optimal parameters. Non-parametric methods generally performed better than parametric methods on our dataset when optimal parameters were used. However, one parametric method, employing the high frequency content of the tremor bandwidth under consideration (High Freq) performed similarly to non-parametric methods, but had the highest recall values, suggesting that this method could be employed for automatic tremor detection. PMID- 27258019 TI - Thirst in Palliative Care #313. PMID- 27258020 TI - The Development of an Angiogenic Protein "Signature" in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling. AB - Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome ProfilerTM Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, p<0.001) and OS (20.5 months [95% CI: 13.5-30] vs. 74 months [95% CI: 36-not reached]; HR: 5.6 [95% CI: 2.8-11.2]; p<0.001). This prognostic performance was superior to that of stage, histology and residual disease after cytoreductive surgery and the levels of vascular endothelial growth factor (VEGF) in ascites. In conclusion, we developed an "angiogenic signature" for patients with AOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies. PMID- 27258021 TI - Prevalence of Virulence/Stress Genes in Campylobacter jejuni from Chicken Meat Sold in Qatari Retail Outlets. AB - Chicken meat from the shelves of supermarkets in Qatar was tested for the presence of Campylobacter spp. and the presence of five virulence genes (htrB, cdtB, clpP, cadF and ciaB) was assessed in isolates. Forty eight percent of the chickens provided for supermarkets by Saudi (53%) and Qatari (45.9%) producers were found to be contaminated and the most important factor affecting the overall prevalence of contaminated chickens was the store from which chicken samples originated. Variation in prevalence of Campylobacter in chicken meat from different stores was evident even when the same producer supplied the three stores in our survey. Differences in the prevalence and in the combinations of virulence genes in isolates that can and cannot grow in a classic maintenance medium (Karmali) were identified, providing a starting point for linking presence/absence of particular virulence genes with actual in vivo virulence and pathogenicity. Because of the relatively low infective doses of Campylobacter that are required to initiate infection in humans, it will be important to explore further the relationships we identified between certain Campylobacter virulence genes and their capacity for survival in poultry meat, and hence their contribution to the incidence of campylobacteriosis. PMID- 27258022 TI - Bending-Twisting Motions and Main Interactions in Nucleoplasmin Nuclear Import. AB - Alpha solenoid proteins play a key role in regulating the classical nuclear import pathway, recognizing a target protein and transporting it into the nucleus. Importin-alpha (Impalpha) is the solenoid responsible for cargo protein recognition, and it has been extensively studied by X-ray crystallography to understand the binding specificity. To comprehend the main motions of Impalpha and to extend the information about the critical interactions during carrier cargo recognition, we surveyed different conformational states based on molecular dynamics (MD) and normal mode (NM) analyses. Our model of study was a crystallographic structure of Impalpha complexed with the classical nuclear localization sequence (cNLS) from nucleoplasmin (Npl), which was submitted to multiple 100 ns of MD simulations. Representative conformations were selected for calculating the 87 lowest frequencies NMs of vibration, and a displacement approach was applied along each NM. Based on geometric criteria, using the radius of curvature and inter-repeat angles as the reference metrics, the main motions of Impalpha were described. Moreover, we determined the salt bridges, hydrogen bonds and hydrophobic interactions in the Impalpha-NplNLS interface. Our results show the bending and twisting motions participating in the recognition of nuclear proteins, allowing the accommodation and adjustment of a classical bipartite NLS sequence. The essential contacts for the nuclear import were also described and were mostly in agreement with previous studies, suggesting that the residues in the cNLS linker region establish important contacts with Impalpha adjusting the cNLS backbone. The MD simulations combined with NM analysis can be applied to the Impalpha-NLS system to help understand interactions between Impalpha and cNLSs and the analysis of non-classic NLSs. PMID- 27258023 TI - A Study of the Variation in the Salivary Peptide Profiles of Young Healthy Adults Acquired Using MALDI-TOF MS. AB - A cross-sectional observational study was conducted to evaluate the inter individual variation in the MALDI-TOF MS peptide profiles of unstimulated whole saliva in a population of 268 systemically healthy adults aged 18-30 yr (150 males and 118 females) with no apparent caries lesions or periodontal disease. Using Spectral Clustering, four subgroups of individuals were identified within the study population. These subgroups were delimited by the pattern of variation in 9 peaks detected in the 2-15 kDa m/z range. An Unsupervised Feature Selection algorithm showed that P-C peptide, a 44 residue-long salivary acidic proline-rich protein, and three of its fragments (Fr. 1-25, Fr. 15-35 and Fr. 15-44) play a central role in delimiting the subgroups. Significant differences were found in the salivary biochemistry of the subgroups with regard to lysozyme and chitinase, two enzymes that are part of the salivary innate defense system (p < 0.001). These results suggest that MALDI-TOF MS salivary peptide profiles may relate information on the underlying state of the oral ecosystem and may provide a useful reference for salivary disease biomarker discovery studies. PMID- 27258024 TI - Correction: Sea Star Wasting Disease in the Keystone Predator Pisaster ochraceus in Oregon: Insights into Differential Population Impacts, Recovery, Predation Rate, and Temperature Effects from Long-Term Research. AB - [This corrects the article DOI: 10.1371/journal.pone.0153994.]. PMID- 27258025 TI - Mediterranean Ocean Colour Chlorophyll Trends. AB - In being at the base of the marine food web, phytoplankton is particularly important for marine ecosystem functioning (e.g., biodiversity). Strong anthropization, over-exploitation of natural resources, and climate change affect the natural amount of phytoplankton and, therefore, represent a continuous threat to the biodiversity in marine waters. In particular, a concerning risks for coastal waters is the increase in nutrient inputs of terrestrial/anthropogenic origin that can lead to undesirable modifications of phytoplankton concentration (i.e., eutrophication). Monitoring chlorophyll (Chl) concentration, which is a proxy of phytoplankton biomass, is an efficient tool for recording and understanding the response of the marine ecosystem to human pressures and thus for detecting eutrophication. Here, we compute Chl trends over the Mediterranean Sea by using satellite data, also highlighting the fact that remote sensing may represent an efficient and reliable solution to synoptically control the "good environmental status" (i.e., the Marine Directive to achieve Good Environmental Status of EU marine waters by 2020) and to assess the application of international regulations and environmental directives. Our methodology includes the use of an ad hoc regional (i.e., Mediterranean) algorithm for Chl concentration retrieval, also accounting for the difference between offshore (i.e., Case I) and coastal (i.e., Case II) waters. We apply the Mann-Kendall test and the Sens's method for trend estimation to the Chl concentration de seasonalized monthly time series, as obtained from the X-11 technique. We also provide a preliminary analysis of some particular trends by evaluating their associated inter-annual variability. The high spatial resolution of our approach allows a clear identification of intense trends in those coastal waters that are affected by river outflows. We do not attempt to attribute the observed trends to specific anthropogenic events. However, the trends that we document are consistent with the findings of several previous studies. PMID- 27258026 TI - Refining Prescription Warning Labels Using Patient Feedback: A Qualitative Study. AB - The complexity of written medication information hinders patients' understanding and leads to patient misuse of prescribed medications. Incorporating patient feedback in designing prescription warning labels (PWLs) is crucial in enhancing patient comprehension of medication warning instructions. This qualitative study explored patient feedback on five newly designed PWLs. In-depth semi-structured face-to-face interviews were conducted with 21 patients, who were 18 years and older, spoke English, and took a prescription medication. These patients were shown different variations of the five most commonly used PWLs-Take with Food, Do not Drink Alcohol, Take with a Full glass of Water, Do not Chew or Break, and Protect from Sunlight. The 60-minute interviews explored feedback on patient comprehension of the PWL instructions and their suggestions for improving the clarity of the PWLs. At the end of the interview, patient self-reported socio demographic information was collected with a 3-minute survey and a brief health literacy assessment was completed using the Newest Vital Sign. Twenty-one patients completed the interviews. Most patients were female (n = 15, 71.4%) with ages ranging from 23 to 66 years old (mean: 47.6 +/- 13.3). The mean health literacy score was 2.4 on a scale of 0-6. Qualitative content analysis based on the text, pictures, and placement of the PWLs on the pill bottle showed preferences for including 'WARNING' on the PWL to create alertness, inclusion of a picture together with the text, yellow color highlighting behind the text, and placement of the PWL on the front of the pill bottle. Although patients had positive opinions of the redesigned PWLs, patients wanted further improvements to the content and design of the PWLs for enhanced clarity and understandability. PMID- 27258027 TI - Correction: High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration. AB - [This corrects the article DOI: 10.1371/journal.pone.0154397.]. PMID- 27258028 TI - Correction: Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial. AB - [This corrects the article DOI: 10.1371/journal.pmed.1002015.]. PMID- 27258029 TI - Boron-Doped Anatase TiO2 as a High-Performance Anode Material for Sodium-Ion Batteries. AB - Pristine and boron-doped anatase TiO2 were prepared via a facile sol-gel method and the hydrothermal method for application as anode materials in sodium-ion batteries (SIBs). The sol-gel method leads to agglomerated TiO2, whereas the hydrothermal method is conducive to the formation of highly crystalline and discrete nanoparticles. The structure, morphology, and electrochemical properties were studied. The crystal size of TiO2 with boron doping is smaller than that of the nondoped crystals, which indicates that the addition of boron can inhibit the crystal growth. The electrochemical measurements demonstrated that the reversible capacity of the B-doped TiO2 is higher than that for the pristine sample. B doping also effectively enhances the rate performance. The capacity of the B doped TiO2 could reach 150 mAh/g at the high current rate of 2C and the capacity decay is only about 8 mAh/g over 400 cycles. The remarkable performance could be attributed to the lattice expansion resulting from B doping and the shortened Li(+) diffusion distance due to the nanosize. These results indicate that B-doped TiO2 can be a good candidate for SIBs. PMID- 27258030 TI - Kidney-Sparing Methods for Extended-Field Intensity-Modulated Radiotherapy (EF IMRT) in Cervical Carcinoma Treatment. AB - Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction. PMID- 27258031 TI - Diamond Blackfan Anemia: A Nonclassical Patient With Diagnosis Assisted by Genomic Analysis. AB - Diamond Blackfan anemia (DBA) is an inherited syndrome usually presenting with severe macrocytic anemia in infancy, paucity of erythroid precursors in the bone marrow, and congenital anomalies. We describe a child with mild, transfusion independent normocytic anemia whose diagnosis of DBA was established by identification of a novel de novo mutation disrupting normal splicing of the ribosomal protein RPL5. The diagnosis of DBA was confirmed by elevated erythrocyte adenosine deaminase levels and an abnormal ribosomal RNA profile. This case demonstrates the usefulness of genomic analysis in establishing the diagnosis of DBA in patients with a nonclassical presentation of the disease. PMID- 27258032 TI - A Previously Healthy Premature Infant Treated With Thrombolytic Therapy for Life threatening Pulmonary Artery Thrombosis. AB - Pulmonary artery thrombosis is rarely reported in preterm neonates. Although treatment of neonatal thrombosis remains controversial, thrombolytic agents must be considered when the thrombosis is life threatening. We herein present a case of a preterm newborn with pulmonary artery thrombosis accompanied by acute-onset respiratory failure and cyanotic congenital heart disease. The thrombosis was successfully treated using tissue plasminogen activator. In conclusion, the thrombolytic therapy should be considered in treatment of patients in whom the thrombosis completely occludes the pulmonary arteries. PMID- 27258033 TI - Childhood Rhabdomyosarcoma in Association With a RASopathy Clinical Phenotype and Mosaic Germline SOS1 Duplication. AB - Childhood rhabdomyosarcoma (RMS) accounts for approximately 3.5% of cancer cases among children 0 to 14 years of age. Genetic conditions associated with high risk of childhood RMS include Li-Fraumeni syndrome, pleuropulmonary blastoma, Beckwith Wiedemann syndrome, and some RASopathies, such as neurofibromatosis type 1, Costello syndrome (CS), and Noonan syndrome (NS). Here, we report the rare case of a 4-year-old girl with clinical features of NS who developed an embryonal RMS of the chest and needed emergent treatment. Molecular genetic testing identified a de novo, large, mosaic duplication of chromosome 2 encompassing the SOS1 gene, presumably caused by a mosaic, unbalanced translocation between chromosomes 2 and 17 found on routine cytogenetic analysis. Sequence analysis of all known genes causing Noonan spectrum disorders was negative. RMS has been reported in a few patients with NS, associated in very few with germline SOS1 mutations, but none with copy number abnormalities. This is the first report to our knowledge of early-onset RMS developing in a child with features of NS and a mosaic RAS pathway gene aberration, a large SOS1 duplication. We hypothesize that the inciting event for tumor development in this case is due to the germline mosaic duplication of SOS1, which was duplicated in all cells of the tumor, and the ultimate development of the tumor was further driven by multiple chromosomal aberrations in the tumor itself, all described as somatic events in isolated RMS tumors. PMID- 27258034 TI - Presentation and Treatment of Histoplasmosis in Pediatric Oncology Patients: Case Series and Review of the Literature. AB - Histoplasmosis is an endemic fungus in several regions of the United States. The diagnosis and treatment of this infection can be challenging in pediatric oncology patients. We present 5 patients diagnosed with histoplasmosis while receiving treatment at a midsize pediatric oncology center in Iowa. Two cases occurred in patients with acute lymphoblastic leukemia and 3 cases in patients with solid tumors. All patients were treated with antifungal therapy and demonstrated excellent clinical response. Histoplasmosis should be considered as a potential cause of nonspecific febrile illness, pulmonary masses, and bone marrow suppression in immunocompromised patients in endemic regions. Prompt and accurate diagnosis can facilitate timely antifungal therapy and avoidance of prolonged hospital stays, invasive testing, unnecessary antibiotics, and unwarranted anticancer therapies. PMID- 27258035 TI - Atrial Fibrillation in Hypertrophic Cardiomyopathy: Is the Extent of Septal Hypertrophy Important? AB - Hypertrophic cardiomyopathy (HCM) is a cardiac disease associated with a high incidence of atrial fibrillation (AF). Recent studies have suggested that interventricular septum thickness may influence the risk stratification of patients with AF. We evaluated the effects of septal hypertrophy on morbidity and mortality in patients with HCM. Patients were followed for a median of 6.1 years and were divided into two groups according to the extent of septal hypertrophy. A total of 1,360 HCM patients were enrolled: 482 (33%) apical or apicoseptal, 415 (28%) asymmetric septal, 388 (27%) basal septal, 38 (2.6%) concentric, and 37 (2.5%) diffuse and mixed type. Ninety-two all-cause deaths and 21 cardiac deaths occurred. The total event rates were significantly higher for patients with HCM with more extensive septal hypertrophy (group A) compared to those with HCM +/- focal septal hypertrophy (group B), regardless of type (p<0.001). Arrhythmias occurred in 502 patients, with a significantly higher incidence in group A than in group B (p<0.001). Among patients with arrhythmias, the incidence of AF was significantly higher in group A than group B (p<0.001). In univariate Cox analysis, a greater extent of septal hypertrophy (p<0.001), E/E' ratio (p = 0.011), and mitral regurgitation grade (p = 0.003) were significantly associated with developing AF. In multivariate Cox analyses, a greater extent of septal hypertrophy [odds ratio (OR) 5.44 (2.29-12.92), p<0.001] in patients with HCM was significantly associated with developing AF. In conclusion, a greater extent of septal hypertrophy is an independent predictor of progression to AF in patients with HCM. PMID- 27258036 TI - Evaluation of the abbot Architect(TM) epstein-barr virus viral capsid antigen IgM, viral capsid antigen IgG and nuclear antigen IgG assays in a pediatric and adult population. AB - BACKGROUND: The detection of antibodies against Epstein-Barr viral capsid (VCA) and nuclear (EBNA) antigens is routinely performed with different commercially available immunoassays. OBJECTIVES: In this study, we evaluated the concordance and performance of the Architect(TM) chemiluminescent microparticle immunoassays (CMIAs) using Captia(TM) enzyme linked immunosorbent assays (ELISA) for VCA IgM, and standard immunofluorescence (IF) assays for VCA IgG and EBNA IgG as comparative techniques. STUDY DESIGN: Sera were selected from a heterogeneous population including pediatric and adult patients. RESULTS: Concordance between CMIAs and comparative assays was high with total agreement percentages of 84,1% (95% CI: 77.8-88.9) for VCA IgM, 90,6% (95% CI: 84.2-94.7) for EBNA IgG and 98,0% (95% CI: 93.9-99.6) for VCA IgG. Moreover, kappa statistic values showed good to excellent correlation with values of 0.68 (95% CI: 0.57-0.79) for VCA IgM, 0.73 (95% CI: 0.58-0.87) for EBNA IgG and 0.95 (95% CI: 0.89-1.00) for VCA IgG. A correlation was observed between positivity levels on CMIAs and semi-quantitative fluorescence intensity on IF for VCA IgG and EBNA IgG assays. With regard to an accepted gold standard IF assays, CMIA was 98,1% (95% CI: 93.3-99.8) sensitive and 97,4% (95% CI: 86.5-99.9) specific for the detection of VCA IgG. For the detection of EBNA IgG, it was 92,2% (95% CI: 85.1-96.6) sensitive and 84,6% (95% CI: 65.1-95.6) specific. CONCLUSION: In summary, we demonstrated that the CMIA EBV antibody detection panel has high performance and high concordance with other commercially available immunoassays. PMID- 27258037 TI - Social and Spatial Clustering of People at Humanity's Largest Gathering. AB - Macroscopic behavior of scientific and societal systems results from the aggregation of microscopic behaviors of their constituent elements, but connecting the macroscopic with the microscopic in human behavior has traditionally been difficult. Manifestations of homophily, the notion that individuals tend to interact with others who resemble them, have been observed in many small and intermediate size settings. However, whether this behavior translates to truly macroscopic levels, and what its consequences may be, remains unknown. Here, we use call detail records (CDRs) to examine the population dynamics and manifestations of social and spatial homophily at a macroscopic level among the residents of 23 states of India at the Kumbh Mela, a 3-month-long Hindu festival. We estimate that the festival was attended by 61 million people, making it the largest gathering in the history of humanity. While we find strong overall evidence for both types of homophily for residents of different states, participants from low-representation states show considerably stronger propensity for both social and spatial homophily than those from high-representation states. These manifestations of homophily are amplified on crowded days, such as the peak day of the festival, which we estimate was attended by 25 million people. Our findings confirm that homophily, which here likely arises from social influence, permeates all scales of human behavior. PMID- 27258039 TI - Correction: Postnatal Anthropometric and Body Composition Profiles in Infants with Intrauterine Growth Restriction Identified by Prenatal Doppler. AB - [This corrects the article DOI: 10.1371/journal.pone.0150152.]. PMID- 27258038 TI - Complete Genomes of Bacillus coagulans S-lac and Bacillus subtilis TO-A JPC, Two Phylogenetically Distinct Probiotics. AB - Several spore-forming strains of Bacillus are marketed as probiotics due to their ability to survive harsh gastrointestinal conditions and confer health benefits to the host. We report the complete genomes of two commercially available probiotics, Bacillus coagulans S-lac and Bacillus subtilis TO-A JPC, and compare them with the genomes of other Bacillus and Lactobacillus. The taxonomic position of both organisms was established with a maximum-likelihood tree based on twenty six housekeeping proteins. Analysis of all probiotic strains of Bacillus and Lactobacillus reveal that the essential sporulation proteins are conserved in all Bacillus probiotic strains while they are absent in Lactobacillus spp. We identified various antibiotic resistance, stress-related, and adhesion-related domains in these organisms, which likely provide support in exerting probiotic action by enabling adhesion to host epithelial cells and survival during antibiotic treatment and harsh conditions. PMID- 27258040 TI - What Is a Complex Innovation System? AB - Innovation systems are sometimes referred to as complex systems, something that is intuitively understood but poorly defined. A complex system dynamically evolves in non-linear ways giving it unique properties that distinguish it from other systems. In particular, a common signature of complex systems is scale invariant emergent properties. A scale-invariant property can be identified because it is solely described by a power law function, f(x) = kxalpha, where the exponent, alpha, is a measure of scale-invariance. The focus of this paper is to describe and illustrate that innovation systems have properties of a complex adaptive system. In particular scale-invariant emergent properties indicative of their complex nature that can be quantified and used to inform public policy. The global research system is an example of an innovation system. Peer-reviewed publications containing knowledge are a characteristic output. Citations or references to these articles are an indirect measure of the impact the knowledge has on the research community. Peer-reviewed papers indexed in Scopus and in the Web of Science were used as data sources to produce measures of sizes and impact. These measures are used to illustrate how scale-invariant properties can be identified and quantified. It is demonstrated that the distribution of impact has a reasonable likelihood of being scale-invariant with scaling exponents that tended toward a value of less than 3.0 with the passage of time and decreasing group sizes. Scale-invariant correlations are shown between the evolution of impact and size with time and between field impact and sizes at points in time. The recursive or self-similar nature of scale-invariance suggests that any smaller innovation system within the global research system is likely to be complex with scale-invariant properties too. PMID- 27258041 TI - BoCluSt: Bootstrap Clustering Stability Algorithm for Community Detection. AB - The identification of modules or communities in sets of related variables is a key step in the analysis and modeling of biological systems. Procedures for this identification are usually designed to allow fast analyses of very large datasets and may produce suboptimal results when these sets are of a small to moderate size. This article introduces BoCluSt, a new, somewhat more computationally intensive, community detection procedure that is based on combining a clustering algorithm with a measure of stability under bootstrap resampling. Both computer simulation and analyses of experimental data showed that BoCluSt can outperform current procedures in the identification of multiple modules in data sets with a moderate number of variables. In addition, the procedure provides users with a null distribution of results to evaluate the support for the existence of community structure in the data. BoCluSt takes individual measures for a set of variables as input, and may be a valuable and robust exploratory tool of network analysis, as it provides 1) an estimation of the best partition of variables into modules, 2) a measure of the support for the existence of modular structures, and 3) an overall description of the whole structure, which may reveal hierarchical modular situations, in which modules are composed of smaller sub-modules. PMID- 27258042 TI - Dual Role of the Tyrosine Kinase Syk in Regulation of Toll-Like Receptor Signaling in Plasmacytoid Dendritic Cells. AB - Crosslinking of regulatory immunoreceptors (RR), such as BDCA-2 (CD303) or ILT7 (CD85g), of plasmacytoid dendritic cells (pDCs) efficiently suppresses production of type-I interferon (IFN)-alpha/beta and other cytokines in response to Toll like receptor (TLR) 7/9 ligands. This cytokine-inhibitory pathway is mediated by spleen tyrosine kinase (Syk) associated with the ITAM-containing adapter of RR. Here we demonstrate by pharmacological targeting of Syk that in addition to the negative regulation of TLR7/9 signaling via RR, Syk also positively regulates the TLR7/9 pathway in human pDCs. Novel highly specific Syk inhibitor AB8779 suppressed IFN-alpha, TNF-alpha and IL-6 production induced by TLR7/9 agonists in primary pDCs and in the pDC cell line GEN2.2. Triggering of TLR9 or RR signaling induced a differential kinetics of phosphorylation at Y352 and Y525/526 of Syk and a differential sensitivity to AB8779. Consistent with the different roles of Syk in TLR7/9 and RR signaling, a concentration of AB8779 insufficient to block TLR7/9 signaling still released the block of IFN-alpha production triggered via the RR pathway, including that induced by hepatitis B and C viruses. Thus, pharmacological targeting of Syk partially restored the main pDC function-IFN alpha production. Opposing roles of Syk in TLR7/9 and RR pathways may regulate the innate immune response to weaken inflammation reaction. PMID- 27258043 TI - Unusually Situated Binding Sites for Bacterial Transcription Factors Can Have Hidden Functionality. AB - A commonly accepted paradigm of molecular biology is that transcription factors control gene expression by binding sites at the 5' end of a gene. However, there is growing evidence that transcription factor targets can occur within genes or between convergent genes. In this work, we have investigated one such target for the cyclic AMP receptor protein (CRP) of enterotoxigenic Escherichia coli. We show that CRP binds between two convergent genes. When bound, CRP regulates transcription of a small open reading frame, which we term aatS, embedded within one of the adjacent genes. Our work demonstrates that non-canonical sites of transcription factor binding can have hidden functionality. PMID- 27258044 TI - Association of the Neutrophil-to-Lymphocyte Ratio with Lung Function and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: The ratio of neutrophils to lymphocytes (NLR) is a widely available marker of inflammation. Several types of inflammatory cells and mediators have been found to be involved in the progression of chronic obstructive pulmonary disease (COPD). We sought to evaluate the association of the NLR with severity of airflow limitation and disease exacerbations in a COPD population. METHODS: We analyzed 885 patients from the Korean COPD Subtype Study cohort that recruited subjects with COPD from 44 referral hospitals. We determined the relationship of NLR levels to severity of lung function using a linear regression model. In addition, we analyzed the experiences of COPD exacerbation according to the NLR quartiles. RESULTS: NLR levels were inversely associated with severity of airflow limitation as measured by FEV1% predicted and absolute values after adjustments for age, gender, body mass index, pack-years of smoking, and the use of inhaled corticosteroid (P<0.001, respectively). In the multivariate binary regression model, the NLR 4th quartile (vs. 1st quartile) was found to be a significant predictor of exacerbations during 1-year follow-up (OR = 2.05, 95% CI = 1.03 to 4.06, P = 0.041). Adding an NLR to FEV1 significantly improved prediction for exacerbations during 1-year follow-up as measured by the net reclassification improvement (NRI = 7.8%, P = 0.032) and the integrated discrimination improvement (IDI = 0.014, P = 0.021). CONCLUSIONS: The NLR showed a significant inverse relationship to airflow limitation and was a prognostic marker for future exacerbations in patients with COPD. PMID- 27258045 TI - The University of the National Football League: How Technology, Injury Surveillance, and Health Care Have Improved the Safety of America's Game. AB - American football has become one of the most popular sports in the United States. Despite the millions of players at all levels of competition who gain the physical, social, and psychological rewards that football provides, many interested stakeholders continue to ask, "Is football safe?" Although there are only approximately 1,700 players on National Football League (NFL) rosters, the injuries they sustain have garnered the most attention-and criticism-from the national media. Increased public awareness of the injury potential football possesses has led to an open debate and a major shift in public sentiment over the past 5 years. Although no sport is perfectly safe, the question is whether it can be made relatively safe and if the long-term consequences are worth the risk. This article reviews the methods by which one sports league-the NFL-has used advances in medical technology and injury surveillance to improve the health and safety of its players. PMID- 27258047 TI - MR Imaging of Pulmonary Nodules: Detection Rate and Accuracy of Size Estimation in Comparison to Computed Tomography. AB - OBJECTIVE: The aims of this study were to assess the sensitivity of various magnetic resonance imaging (MRI) sequences for the diagnosis of pulmonary nodules and to estimate the accuracy of MRI for the measurement of lesion size, as compared to computed tomography (CT). METHODS: Fifty patients with 113 pulmonary nodules diagnosed by CT underwent lung MRI and CT. MRI studies were performed on 1.5T scanner using the following sequences: T2-TSE, T2-SPIR, T2-STIR, T2-HASTE, T1-VIBE, and T1-out-of-phase. CT and MRI data were analyzed independently by two radiologists. RESULTS: The overall sensitivity of MRI for the detection of pulmonary nodules was 80.5% and according to nodule size: 57.1% for nodules <=4mm, 75% for nodules >4-6mm, 87.5% for nodules >6-8mm and 100% for nodules >8mm. MRI sequences yielded following sensitivities: 69% (T1-VIBE), 54.9% (T2 SPIR), 48.7% (T2-TSE), 48.7% (T1-out-of-phase), 45.1% (T2-STIR), 25.7% (T2 HASTE), respectively. There was very strong agreement between the maximum diameter of pulmonary nodules measured by CT and MRI (mean difference -0.02 mm; 95% CI -1.6-1.57 mm; Bland-Altman analysis). CONCLUSIONS: MRI yielded high sensitivity for the detection of pulmonary nodules and enabled accurate assessment of their diameter. Therefore it may be considered an alternative to CT for follow-up of some lung lesions. However, due to significant number of false positive diagnoses, it is not ready to replace CT as a tool for lung nodule detection. PMID- 27258046 TI - Synthesis of Diiron(I) Dithiolato Carbonyl Complexes. AB - Virtually all organosulfur compounds react with Fe(0) carbonyls to give the title complexes. These reactions are reviewed in light of major advances over the past few decades, spurred by interest in Fe2(MU-SR)2(CO)x centers at the active sites of the [FeFe]-hydrogenase enzymes. The most useful synthetic route to Fe2(MU SR)2(CO)6 involves the reaction of thiols with Fe2(CO)9 and Fe3(CO)12. Such reactions can proceed via mono-, di-, and triiron intermediates. The reactivity of Fe(0) carbonyls toward thiols is highly chemoselective, and the resulting dithiolato complexes are fairly rugged. Thus, many complexes tolerate further synthetic elaboration directed at the organic substituents. A second major route involves alkylation of Fe2(MU-S2)(CO)6, Fe2(MU-SH)2(CO)6, and Li2Fe2(MU-S)2(CO)6. This approach is especially useful for azadithiolates Fe2[(MU-SCH2)2NR](CO)6. Elaborate complexes arise via addition of the FeSH group to electrophilic alkenes, alkynes, and carbonyls. Although the first example of Fe2(MU-SR)2(CO)6 was prepared from ferrous reagents, ferrous compounds are infrequently used, although the Fe(II)(SR)2 + Fe(0) condensation reaction is promising. Almost invariably low-yielding, the reaction of Fe3(CO)12, S8, and a variety of unsaturated substrates results in C-H activation, affording otherwise inaccessible derivatives. Thiones and related C?S-containing reagents are highly reactive toward Fe(0), often giving complexes derived from substituted methanedithiolates and C-H activation. PMID- 27258048 TI - The Small G Protein AtRAN1 Regulates Vegetative Growth and Stress Tolerance in Arabidopsis thaliana. AB - The evolutionarily conserved small G-protein Ran plays important role in nuclear translocation of proteins, cell cycle regulation, and nuclear envelope maintenance in mammalian cells and yeast. Arabidopsis Ran proteins are encoded by a family of four genes and are highly conserved at the protein level. However, their biological functions are poorly understood. We report here that AtRAN1 plays an important role in vegetative growth and the molecular improvement of stress tolerance in Arabidopsis. AtRAN1 overexpression promoted vegetative growth and enhanced abiotic tolerance, while the atran1 atran3 double mutant showed higher freezing sensitivity than WT. The AtRAN1 gene is ubiquitously expressed in plants, and the expression levels are higher in the buds, flowers and siliques. Subcellular localization results showed that AtRAN1 is mainly localized in the nucleus, with some present in the cytoplasm. AtRAN1 could maintain cell division and cell cycle progression and promote the formation of an intact nuclear envelope, especially under freezing conditions. PMID- 27258049 TI - Urinary Strong Ion Difference as a Marker of Renal Dysfunction. A Retrospective Analysis. AB - INTRODUCTION: The kidneys play a crucial role in the regulation of electrolytes and acid-base homeostasis. Urinary Strong Ion Difference (SIDu = NaU + KU-ClU) represents an important aspect of renal acid-base regulation. We evaluated the role of SIDu as a marker of renal dysfunction in critically ill patients. MATERIALS AND METHODS: Patients admitted to the Medical Intensive Care Unit with a diagnosis of AKI for whom concomitant urinary samples available for SIDu calculation were retrospectively reviewed and staged according to KDIGO criteria for 3 days from inclusion. Patients were classified as Recovered (R-AKI) or Persistent-AKI (P-AKI) whether they exited KDIGO criteria within the 3-day observation period or not. A control group with normal renal function and normal serum acid-base and electrolytes was prospectively recruited in order to identify reference SIDu values. RESULTS: One-hundred-and-forty-three patients with a diagnosis of AKI were included: 77 with R-AKI, and 66 with P-AKI. Thirty-six controls were recruited. Patients with P-AKI had more severe renal dysfunction and higher mortality than patients with R-AKI (SCr 2.23(IQR:1.68-3.45) and 1.81(IQR1.5-2.5) mg/dl respectively, p<0.001; 24-h UO 1297(950) and 2100(1094) ml respectively, p = 0.003); 30-d mortality, 39% and 13% respectively; p<0.001). SIDu significantly differed between groups, with rising values from controls to P AKI groups (16.4(12), 30(24) and 47.3(21.5) mEq/l respectively, p<0.001). DISCUSSION: SIDu may be a simple and inexpensive tool in AKI patients' evaluation. Further research is needed to evaluate the ability of SIDu to identify patients with renal dysfunction before derangements in serum creatinine or urine output are observed. PMID- 27258050 TI - Gender Roles and Physical Function in Older Adults: Cross-Sectional Analysis of the International Mobility in Aging Study (IMIAS). AB - OBJECTIVES: To examine the relationships between physical function and gender stereotyped traits and whether these relationships are modified by sex or social context. METHODS: A total of 1995 community-dwelling older adults from the International Mobility in Aging Study (IMIAS) aged 65 to 74 years were recruited in Natal (Brazil), Manizales (Colombia), Tirana (Albania), Kingston (Ontario, Canada), and Saint-Hyacinthe (Quebec, Canada). We performed a cross-sectional analysis. Study outcomes were mobility disability, defined as having difficulty in walking 400 meters without assistance or climbing a flight of stairs without resting, and low physical performance, defined as a score < 8 on the Short Physical Performance Battery. The 12-item Bem Sex Role Inventory (BSRI) was used to classify participants into four gender roles (Masculine, Feminine, Androgynous, and Undifferentiated) using site-specific medians of femininity and masculinity as cut-off points. Poisson regression models were used to estimate prevalence rate ratios (PRR) of mobility disability and poor physical performance according to gender roles. RESULTS: In models adjusted for sex, marital status, education, income, and research site, when comparing to the androgynous role, we found higher prevalence of mobility disability and poor physical performance among participants endorsing the feminine role (PRR = 1.20, 95% confidence interval (CI) 1.03-1.39 and PRR = 1.37, CI 1.01-1.88, respectively) or the undifferentiated role (PRR = 1.23, 95% CI 1.07-1.42 and PRR = 1.58, CI 1.18-2.12, respectively). Participants classified as masculine did not differ from androgynous participants in prevalence rates of mobility disability or low physical performance. None of the multiplicative interactions by sex and research site were significant. CONCLUSION: Feminine and undifferentiated gender roles are independent risk factors for mobility disability and low physical performance in older adults. Longitudinal research is needed to assess the mediation pathways through which gender-stereotyped traits influence functional limitations and to investigate the longitudinal nature of these relationships. PMID- 27258051 TI - Survivorship care planning in a comprehensive cancer center using an implementation framework. AB - Cancer survivorship care plans (SCPs) have been recommended to improve clinical care and patient outcomes. Research is needed to establish their efficacy and identify best practices. Starting in 2015, centers accredited by the American College of Surgeons Commission on Cancer must deliver SCPs to patients completing primary cancer treatment with curative intent. We describe how we established routine SCP delivery at the Robert H Lurie Comprehensive Cancer Center in Chicago, Illinois, using the Quality Implementation Framework. We evaluated local practices, gathered clinician and patient stakeholder input, developed customized SCP templates within the electronic health record (EHR), and implemented 2 complementary delivery models. Clinician interviews (n = 41) and survey responses (n = 12), along with input from patients (n = 68) and a patient advisory board (n = 15), indicated support for SCPs and survivorship services. To promote feasible implementation and leverage existing workflows, we harmonized 2 SCP delivery models: integrated care within clinics where patients received treatment, and referral to a centralized survivorship clinic. We are implementing SCP delivery with prominent disease sites and will extend services to survivors of other cancers in the future. We developed four electronic disease-specific SCP templates for breast, colorectal, lung, and prostate cancers and a fifth, generic template that can be used for other malignancies. The templates reduced free-text clinician entry by auto-populating 20% of the fields from existing EHR data, and using drop-down menus for another 65%. Mean SCP completion time is 12 minutes (range, 10-15; n = 64). We designed our framework to facilitate ongoing evaluation of implementation and quality improvement. Funding/sponsorship Robert H Lurie Comprehensive Cancer Center, the Coleman Foundation, and the Lynn Sage Cancer Research Foundation. PMID- 27258052 TI - Effects of exercise interventions during different treatments in breast cancer. AB - Previous findings suggest that exercise is a safe and efficacious means of improving physiological and psychosocial outcomes in female breast cancer survivors. To date, most research has focused on post-treatment interventions. However, given that the type and severity of treatment-related adverse effects may be dependent on the type of treatment, and that the effects are substantially more pronounced during treatment, an assessment of the safety and efficacy of exercise during treatment is warranted. In this review, we present and evaluate the results of randomized controlled trials (RCTs) conducted during breast cancer treatment. We conducted literature searches to identify studies examining exercise interventions in breast cancer patients who were undergoing chemotherapy or radiation. Data were extracted on physiological and psychosocial outcomes. Cohen's d effect sizes were calculated for each outcome. A total of 17 studies involving 1,175 participants undergoing active cancer therapy met the inclusion criteria. Findings revealed that, on average, exercise interventions resulted in moderate to large improvements in muscular strength: resistance exercise (RE, ?? = 0.86), aerobic exercise (AE, ?? = 0.55), small to moderate improvements in cardiovascular functioning (RE, ?? = 0.45; AE, ?? = 0.17, combination exercise (COMB, ?? = 0.31) and quality of life (QoL; RE, ?? = 0.30; AE, ?? = 0.50; COMB, ?? = 0.63). The results of this review suggest that exercise is a safe, feasible, and efficacious intervention in breast cancer patients who are undergoing different types of treatment. Additional research addressing the different modes of exercise during each type of treatment is warranted to assess the comparable efficacy of the various exercise modes during established breast cancer treatments. PMID- 27258053 TI - Omission of dexamethasone from antiemetic treatment for highly emetogenic chemotherapy in breast cancer patients with hepatitis B infection or diabetes mellitus. AB - BACKGROUND: Chemotherapy with anthracycline- and cyclophosphamide-containing regimens are classified as highly emetogenic. Combinatory treatments of aprepitant (Apr), palonosetron (Pal), or granisetron (Gra) with dexamethasone are recommended as antiemetic treatments for such emetogenic chemotherapy. We retrospectively examined whether omission of dexamethasone is tolerable for patients with hepatitis B virus (HBV) and diabetes mellitus (DM), for whom it is recommended not receive dexamethasone. PATIENTS AND METHODS: During August 2009 and September 2007, we reviewed the medical records of patients with breast cancer who were HBV carriers or had been diagnosed with DM. 97 patients were treated with anthracycline- and cyclophosphamide- containing regimens with omission of dexamethasone in antiemetic treatment because of their HBV or DM status. RESULTS: Results The number of patients treated with Gra only, Apr and Gra, Apr and Pal, were 29, 29, and 39, respectively. Complete response (CR) in the acute phase (0-<24 hours after chemotherapy) or delayed phase (24-120 hours after chemotherapy) for Gra only, Apr-Gra, and Apr-Pal was 44.8% and 44.8%, 72.4% and 72.4%, and 76.9% and 74.4%, respectively. Complete control (CC) in the acute or delayed phase in each regimen for Gra only, Apr-Gra, and Apr-Pal was 31.0% and 27.6%, 48.2% and 51.7%, and 46.2% and 46.2%, respectively. Apr-Gra or Apr-Pal tended to be superior to Gra only in CR and CC in both the acute and delayed phases. HBV reactivation or aggravation of DM control was not observed in any of the 3 therapy options. CR and CC were about 20% higher for the dexamethasone containing regimen than for the non-dexamethasone regimen in both the acute and delayed phases. CONCLUSION: Omission of dexamethasone in antiemetic treatment is tolerable when anthracycline- and cyclophosphamide-containing chemotherapy is administered to patients with breast cancer who have comorbidities of being HBV carriers or of DM. PMID- 27258054 TI - Prognostic significance of HPV status in postoperative squamous-cell carcinoma of the head and neck. AB - BACKGROUND: There are limited data on the prognostic significance of human papillomavirus (HPV) status in relation to traditional risk factors for head and neck squamous-cell carcinoma (HNSCC) in the postoperative setting. OBJECTIVE: To clarify the impact of HPV status on the risk for HNSCC in the postoperative setting. METHODS: We retrospectively evaluated an institutional cohort of 128 patients with HNSCC patients who had been treated with definitive surgery with or without adjuvant radiotherapy or chemoradiotherapy. Patient, disease, and treatment factors were analyzed as potential prognostic indicators. RESULTS: Lymph node extracapsular extension (ECE), perineural invasion (PNI), and lymphovascular space invasion (LVSI) positivity predicted poorer locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Positive margins related to poorer DFS and OS. HPV status alone did not predict LRC, DFS, or OS. Compared with patients who were HPV-positive and ECE-negative, both HPV positive and HPV-negative patients with ECE experienced significantly poorer OS (78.6%, 60%, and 43.7%, respectively; ?? = .010 and ?? = .018, respectively). LIMITATIONS: Retrospective, single-institution study; small patient cohort; short follow-up time. CONCLUSION: The influence of HPV in postoperative HNSCC seems limited compared with traditional risk factors such as ECE, LVSI, and PNI. De escalation of postoperative treatment based on HPV status alone should be approached with caution. PMID- 27258055 TI - Culture-broker and medical decoder: contributions of caregivers in American Indian cancer trajectories. AB - BACKGROUND: Caregivers play a special role in the management and control of cancer-related pain. For American Indians with cancer, caregivers can contribute to patient education, medication compliance, and can facilitate communication between the patient and the provider and the patient and the family. OBJECTIVE: To identify the role(s) of caregivers of American Indian cancer survivors. METHODS: As a part of a large randomized intervention designed to improve barriers to cancer symptom management, 13 focus groups were held among American Indian cancer survivors and their caregivers at Southwest reservations and urban sites. Focus groups, audiotaped and transcribed, used constant comparative methods in the analysis of caregiver dialogues. RESULTS: Caregivers are patient educators and provider culture-brokers and their communication strategies use a combination of cultural and conventional strategies in their care of American Indian cancer patients. Cultural communication styles include "talk stories" (storytelling), group (talking circles), and dialogue to manage cancer pain, educate the patient and community, and to protect the patient from stigma, reduce barriers to care, and provide support to patients and families. Active discussion with providers "re-packaged" the patient's reporting/responses to specific clinical measures (pain measure scores) and identified the need for pain medication and compliance-related issues. LIMITATIONS: Findings are not generalizable to the American Indian population outside of the sites and focus groups from which data were collected. CONCLUSIONS: Caregivers are "cultural brokers" who inform providers of the cultural nuances associated with American Indian patient care. However, caregivers voiced that cultural restriction for not discussing illness openly was a sanction and an important barrier. PMID- 27258056 TI - Paraneoplastic syndrome and underlying breast cancer: a worsening rash despite initiation of chemotherapy. AB - Skin may show the first clinical evidence of systemic disease and can be the first clue to malignancy in 1% of cases. Dermatomyositis is an immunologically mediated inflammatory myopathy characterized by proximal muscle weakness, muscle inflammation, and characteristic skin findings. It has an incidence of 1 in 100,000 patients. In 15%-30% cases of dermatomyositis, an underlying malignancy is the cause of paraneoplastic syndrome. Ovarian and breast cancer in women and lung cancer in men are the most common malignancies associated with dermatomyositis. Here we report the case of a 55-year-old postmenopausal woman who initially presented with a facial rash. She was treated for chemical dermatitis without resolution of symptoms and was subsequently found to have dermatomyositis associated with stage IV invasive ductal carcinoma of the breast. In most cases, the skin changes resolve after treatment for the underlying malignancy has been initiated, but in this case of paraneoplastic dermatomyositis, the rash worsened with initiation of treatment for underlying breast cancer. PMID- 27258057 TI - Correction: Effects of Verapamil SR and Atenolol on 24-Hour Blood Pressure and Heart Rate in Hypertension Patients with Coronary Artery Disease: An International Verapamil SR-Trandolapril Ambulatory Monitoring Substudy. AB - [This corrects the article DOI: 10.1371/journal.pone.0122726.]. PMID- 27258058 TI - A Comparative Study of Five Association Tests Based on CpG Set for Epigenome-Wide Association Studies. AB - An epigenome-wide association study (EWAS) is a large-scale study of human disease-associated epigenetic variation, specifically variation in DNA methylation. High throughput technologies enable simultaneous epigenetic profiling of DNA methylation at hundreds of thousands of CpGs across the genome. The clustering of correlated DNA methylation at CpGs is reportedly similar to that of linkage-disequilibrium (LD) correlation in genetic single nucleotide polymorphisms (SNP) variation. However, current analysis methods, such as the t test and rank-sum test, may be underpowered to detect differentially methylated markers. We propose to test the association between the outcome (e.g case or control) and a set of CpG sites jointly. Here, we compared the performance of five CpG set analysis approaches: principal component analysis (PCA), supervised principal component analysis (SPCA), kernel principal component analysis (KPCA), sequence kernel association test (SKAT), and sliced inverse regression (SIR) with Hotelling's T2 test and t-test using Bonferroni correction. The simulation results revealed that the first six methods can control the type I error at the significance level, while the t-test is conservative. SPCA and SKAT performed better than other approaches when the correlation among CpG sites was strong. For illustration, these methods were also applied to a real methylation dataset. PMID- 27258059 TI - Wheat Grain Yield Increase in Response to Pre-Anthesis Foliar Application of 6 Benzylaminopurine Is Dependent on Floret Development. AB - Wheat yield is largely determined during the period prior to flowering, when the final numbers of fertile florets and grains per spike are established. The aim of this study was to assess the dynamics of floret primordia development in winter wheat in response to pre-anthesis application of a synthetic cytokinin, 6 benzylaminopurine (6-BA). We conducted an experiment in which two foliar spray treatments were applied (water or 6-BA) to Chinese winter wheat at 25 days after jointing during two growing seasons (2012-2013 and 2013-2014). Both the final grain number per spike and grain yield at maturity exhibited remarkable increases in response to the 6-BA treatment. Application of 6-BA increased the number of fertile florets in basal spikelets and, to a greater extent, in central spikelets. The mechanism by which 6-BA application affected the final number of fertile florets primarily involved suppression of the floret abortion rates. Application of 6-BA considerably reduced the abortion rates of basal, central and apical spikelet florets (by as much as 77% compared with the control), as well as the degeneration rates of basal and central spikelet florets, albeit to a lesser degree. The effect of 6-BA application on the likelihood of proximal florets being set was limited to the distal florets in the whole spike, whereas obvious increases in the likelihood of grain set under 6-BA treatment were observed in distal florets, primarily in central spikelet positions. The results of this study provide important evidence that 6-BA application to florets (final fertile floret production) results in an increased grain yield. PMID- 27258061 TI - John Jackson and Sonja Swanson, Winners of the 2016 Kenneth Rothman EPIDEMIOLOGY Prize. PMID- 27258060 TI - In vivo simultaneous multispectral fluorescence imaging with spectral multiplexed volume holographic imaging system. AB - A simultaneous multispectral fluorescence imaging system incorporating multiplexed volume holographic grating (VHG) is developed to acquire multispectral images of an object in one shot. With the multiplexed VHG, the imaging system can provide the distribution and spectral characteristics of multiple fluorophores in the scene. The implementation and performance of the simultaneous multispectral imaging system are presented. Further, the system's capability in simultaneously obtaining multispectral fluorescence measurements is demonstrated with in vivo experiments on a mouse. The demonstrated imaging system has the potential to obtain multispectral images fluorescence simultaneously. PMID- 27258062 TI - Grim19 Attenuates DSS Induced Colitis in an Animal Model. AB - DSS induced colitis is a chronic inflammatory disease characterized by inflammation in the gastrointestinal tract, which destabilizes the gut and induces an uncontrolled immune response. Although DSS induced colitis is generally thought to develop as a result of an abnormally active intestinal immune system, its pathogenesis remains unclear. Gene associated with retinoid interferon induced mortality (Grim) 19 is an endogenous specific inhibitor of STAT3, which regulates the expression of proinflammatory cytokines. In this study, we investigated the influence of GRIM19 in a DSS induced colitis mouse model. We hypothesized that Grim19 would ameliorate DSS induced colitis by altering STAT3 activity and intestinal inflammation. Grim19 ameliorated DSS induced colitis severity and protected intestinal tissue. The expression of STAT3 and proinflammatory cytokines such as IL-1beta and TNF-alpha in colon and lymph nodes was decreased significantly by Grim19. Moreover, DSS induced colitis progression in a Grim19 transgenic mouse line was inhibited in association with a reduction in STAT3 and IL-17 expression. These results suggest that Grim19 attenuates DSS induced colitis by suppressing the excessive inflammatory response mediated by STAT3 activation. PMID- 27258063 TI - Pedestrian road crossing behavior (PEROB): Development and psychometric evaluation. AB - OBJECTIVE: The aim of this study was to develop a theory-based questionnaire to measure road crossing attitudes and potentially risky pedestrian behavior. METHODS: A cross-sectional validation study was carried out on a total sample of 380 young adults aged 18 to 25 years who live in Tehran, Iran. Data were collected from January 27 to May 20, 2015, using a self-administered structured pool of 76 items that was developed from research on the theory of planned behavior. A panel of subject-matter experts evaluated the items for content validity index and content validity ratio, and the questionnaire was pretested. Exploratory factor analysis (EFA) was performed to test construct validity. The Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) analyses were done to assess internal consistency and stability of the scale. RESULTS: From the initial 76 items, 38 items were found to be appropriate for assessing the pedestrian road crossing behavior (PEROB) of young adults in Tehran. A 9-factor solution revealed an exploratory factor analysis that jointly accounted for 63.8% of the variance observed. Additional analyses also indicated acceptable results for the internal consistency with Cronbach's alpha value ranging from 0.67 to 0.88 and ICC values ranging from 0.64 to 0.96. CONCLUSIONS: This psychometric evaluation of a self-administered instrument resulted in a reliable and valid instrument to assess young adult pedestrians' self-reported road crossing attitudes and behaviors in Tehran. Further development of the instrument is needed to assess its applicability to other road users, particularly older pedestrians. PMID- 27258064 TI - Aptamers Coming of Age at Twenty-Five. PMID- 27258065 TI - First International Workshop on Zika Virus Held by Oswaldo Cruz Foundation FIOCRUZ in Northeast Brazil March 2016 - A Meeting Report. PMID- 27258066 TI - OsLBD3-7 Overexpression Induced Adaxially Rolled Leaves in Rice. AB - Appropriate leaf rolling enhances erect-leaf habits and photosynthetic efficiency, which consequently improves grain yield. Here, we reported the novel lateral organ boundaries domain (LBD) gene OsLBD3-7, which is involved in the regulation of leaf rolling. OsLBD3-7 works as a transcription activator and its protein is located on the plasma membrane and in the nucleus. Overexpression of OsLBD3-7 leads to narrow and adaxially rolled leaves. Microscopy of flag leaf cross-sections indicated that overexpression of OsLBD3-7 led to a decrease in both bulliform cell size and number. Transcriptional analysis showed that key genes that had been reported to be negative regulators of bulliform cell development were up-regulated in transgenic plants. These results indicated that OsLBD3-7 might acts as an upstream regulatory gene of bulliform cell development to regulate leaf rolling, which will give more insights on the leaf rolling regulation mechanism. PMID- 27258067 TI - Expression of Cell Competition Markers at the Interface between p53 Signature and Normal Epithelium in the Human Fallopian Tube. AB - There is a growing body of evidence regarding cell competition between normal and mutant mammalian cells, which suggest that it may play a defensive role in the early phase of carcinogenesis. In vitro study in the past has shown that overexpression of vimentin in normal epithelial cells at the contact surface with transformed cells is essential for the cell competition involved in epithelial defense against cancer. In this study, we attempted to examine cell competition in human tissue in vivo by investigating surgically resected human fallopian tubes that contain p53 signatures and serous tubal intraepithelial lesions (STILs), a linear expansion of p53-immunopositive/TP53 mutant tubal epithelial cells that are considered as precursors of pelvic high grade serous carcinoma. Immunofluorescence double staining for p53 and the cell competition marker vimentin was performed in 21 sections of human fallopian tube tissue containing 17 p53 signatures and 4 STILs. The intensities of vimentin expression at the interface between p53-positive cells at the end of the p53 signature/STIL and adjacent p53-negative normal tubal epithelial cells were compared with the background tubal epithelium. As a result, the average vimentin intensity at the interfaces relative to the background intensity was 1.076 (95% CI, 0.9412 - 1.211 for p53 signature and 0.9790 (95% CI, 0.7206 - 1.237) for STIL. Thus, it can be concluded that overexpression of the cell competition marker vimentin are not observed in human tissue with TP53 alterations. PMID- 27258068 TI - Isolation of C. difficile Carriers Alone and as Part of a Bundle Approach for the Prevention of Clostridium difficile Infection (CDI): A Mathematical Model Based on Clinical Study Data. AB - Clostridium difficile infection is the most common hospital-acquired infection. Besides infected patients, carriers have emerged as a key player in C. difficile epidemiology. In this study, we evaluated the impact of identifying and isolating carriers upon hospital admission on the incidence of CDI incidence and hospital acquired C. difficile colonization, as a single policy and as part of bundle approaches. We simulated C. difficile transmission using a stochastic mathematical approach, considering the contribution of carriers based on published literature. In the baseline scenario, CDI incidence was 6.18/1,000 admissions (95% CI, 5.72-6.65), simulating reported estimates from U.S. hospital discharges. The acquisition rate of C. difficile carriage was 9.72/1,000 admissions (95% CI, 9.15-10.31). Screening and isolation of colonized patients on admission to the hospital decreased CDI incidence to 4.99/1,000 admissions (95% CI, 4.59-5.42; relative reduction (RR) = 19.1%) and led to 36.2% reduction in the rate of hospital-acquired colonization. Simulating an antimicrobial stewardship program reduced CDI rate to 2.35/1,000 admissions (95% CI, 2.07-2.65). In sensitivity analysis, CDI incidence was less than 2.32/1,000 admissions (RR = 62.4%) in 95% of 1,000 simulations. The combined bundle, focusing on reducing C. difficile transmission from colonized patients and the individual risk of these patients to develop CDI, decreased significantly the incidence of both CDI and hospital-acquired colonization. Implementation of this bundle to current practice is expected to have an important impact in containing CDI. PMID- 27258070 TI - Still Waiting for Evidence That Current Noninvasive Hemoglobinometry Adds Value. PMID- 27258069 TI - Trypanosoma brucei TIF2 and TRF Suppress VSG Switching Using Overlapping and Independent Mechanisms. AB - Trypanosoma brucei causes debilitating human African trypanosomiasis and evades the host's immune response by regularly switching its major surface antigen, VSG, which is expressed exclusively from subtelomeric loci. We previously showed that two interacting telomere proteins, TbTRF and TbTIF2, are essential for cell proliferation and suppress VSG switching by inhibiting DNA recombination events involving the whole active VSG expression site. We now find that TbTIF2 stabilizes TbTRF protein levels by inhibiting their degradation by the 26S proteasome, indicating that decreased TbTRF protein levels in TbTIF2-depleted cells contribute to more frequent VSG switching and eventual cell growth arrest. Surprisingly, although TbTIF2 depletion leads to more subtelomeric DNA double strand breaks (DSBs) that are both potent VSG switching inducers and detrimental to cell viability, TbTRF depletion does not increase the amount of DSBs inside subtelomeric VSG expression sites. Furthermore, expressing an ectopic allele of F2H-TbTRF in TbTIF2 RNAi cells allowed cells to maintain normal TbTRF protein levels for a longer frame of time. This resulted in a mildly better cell growth and partially suppressed the phenotype of increased VSG switching frequency but did not suppress the phenotype of more subtelomeric DSBs in TbTIF2-depleted cells. Therefore, TbTIF2 depletion has two parallel effects: decreased TbTRF protein levels and increased subtelomeric DSBs, both resulting in an acute increased VSG switching frequency and eventual cell growth arrest. PMID- 27258071 TI - Lung Transplantation Is Much More Than Lungs and Fluids. PMID- 27258072 TI - Obstructive Fibrinous Tracheal Pseudomembrane. AB - Obstructive fibrinous tracheal pseudomembrane (OFTP) is a rare and potentially severe complication of endotracheal intubation characterized by a tubular pseudomembrane that obstructs the trachea and induces clinical symptoms of airway obstruction after extubation. In this report, we reviewed and summarized all published cases of OFTP (n = 58) between 1981 and 2015. Twenty-three of 52 patients were men, and the mean age was 36 +/- 22 years. Intubation was emergent in 41 of 53 cases. OFTP was revealed by acute symptoms in 19 of 39 cases and led to acute respiratory failure in 13 of 39 cases. Symptoms occurred 3 +/- 3 days after extubation. A tracheal obstruction >=70% was observed in 14 of 18 cases. Bronchoscopic removal was performed in 49 of 58 cases with no recurrence. In conclusion, OFTP is characterized by a typical clinical and endoscopic presentation, with no recurrence after bronchoscopic removal. Early recognition and bronchoscopy are key elements for efficient diagnosis and treatment. PMID- 27258073 TI - Opioid-induced Hallucinations: A Review of the Literature, Pathophysiology, Diagnosis, and Treatment. AB - Despite their association with multiple adverse effects, opioid prescription continues to increase. Opioid-induced hallucination is an uncommon yet significant adverse effect of opioid treatment. The practitioner may encounter patient reluctance to volunteer the occurrence of this phenomenon because of fears of being judged mentally unsound. The majority of the literature concerning opioid-induced hallucinations arises from treatment during end-of-life care and cancer pain. Because the rate of opioid prescriptions continues to increase in the population, the rate of opioid-associated hallucinations may also conceivably increase. With a forecasted increase in the patient-to-physician ratio, opioid therapy is predicted to be provided by practitioners of varying backgrounds and medical specialties. Hence, knowledge of the pharmacology and potential adverse effects of these agents is required. This review seeks to increase awareness of this potential complication through a discussion of the literature, potential mechanisms of action, diagnosis, and treatment strategies. PMID- 27258075 TI - A Clinical Prediction Model for Postcardiac Surgery Atrial Fibrillation in an Asian Population. AB - BACKGROUND: Postoperative atrial fibrillation (AF) is associated with increased morbidity, mortality, and resource utilization. Current prediction models for postoperative AF are based primarily on Western populations. In this study, we sought to develop a clinical prediction rule for postcardiac surgery AF for a multiethnic Asian population. METHODS: Two thousand one hundred sixty-eight patients undergoing coronary artery bypass graft or valve surgery with cardiopulmonary bypass were prospectively enrolled in this observational study between August 2008 and July 2012 at Singapore's 2 national heart centers. Postoperative AF was defined as an irregularly irregular electrocardiogram rhythm without identifiable P wave after surgery and before hospital discharge that lasted more than an hour, or affected hemodynamics (ie, systolic blood pressure <90 mm Hg or mean arterial blood pressure <60 mm Hg), or required medical treatment. Patients had continuous telemetry monitoring for at least 72 hours while in the intensive care or high-dependency units postoperatively. Subsequently, patients had a 12-lead electrocardiogram daily and when symptomatic. Multivariable logistic regression was used to determine significant predictors of postcardiac surgery AF, and a scoring system was developed. The model was internally validated in an additional 500 patients. RESULTS: Postoperative AF occurred in 17.3% of patients, with a peak occurrence in the first 72 hours after surgery. Multivariate logistic regression analysis identified age >=65 years (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.11-1.85, P = 0.005), history of AF (OR, 3.65; 95% CI, 2.52-5.30, P < 0.001), inotrope use (OR, 1.74; 95% CI, 1.31-2.32, P < 0.001), cardiopulmonary bypass duration >120 minutes (OR, 1.92; 95% CI, 1.47-2.52, P < 0.001), and Chinese ethnicity (Chinese versus Indian OR, 2.09; 95% CI, 1.28-3.41, P = 0.003) or Malay (Malay versus Indian OR, 2.43; 95% CI, 1.36-4.05, P = 0.002) to be independently associated with postoperative AF. The area under the receiver-operator characteristic curve of the model was 0.704 (95% CI, 0.674-0.734). Internal validation produced an area under the receiver-operator characteristic curve of 0.756 (95% CI, 0.690-0.821). CONCLUSIONS: Clinical risk factors for AF after cardiac surgery in an Asian population are similar to that reported from primarily Western populations, but specific ethnicity influences susceptibility. PMID- 27258076 TI - Anesthetic Management of 65 Cases of Ex Utero Intrapartum Therapy: A 13-Year Single-Center Experience. AB - The anesthetic management for open fetal surgery has been described, but many therapeutic tenets have not been supported with data. We present data on the anesthetic management and outcomes of 65 patients undergoing ex utero intrapartum therapy procedures at the Children's Hospital of Philadelphia between 1998 and 2011. Patients were identified, and medical records were retrospectively reviewed. Maternal general anesthesia combined with postoperative epidural analgesia was commonly used. High levels of volatile anesthetic were used for uterine relaxation. Case characteristics such as fetal procedure, operative time, blood loss, transfusion requirements, vasopressor use, and fetal resuscitative measures are described. PMID- 27258077 TI - Head, Neck, and Body Position: The Need to Standardize the Language. PMID- 27258079 TI - Smart Anesthesia-Another Way of Communication During Emergence from Anesthesia Using a Smartphone. PMID- 27258081 TI - Calibration of Contactless Pulse Oximetry. AB - BACKGROUND: Contactless, camera-based photoplethysmography (PPG) interrogates shallower skin layers than conventional contact probes, either transmissive or reflective. This raises questions on the calibratability of camera-based pulse oximetry. METHODS: We made video recordings of the foreheads of 41 healthy adults at 660 and 840 nm, and remote PPG signals were extracted. Subjects were in normoxic, hypoxic, and low temperature conditions. Ratio-of-ratios were compared to reference SpO2 from 4 contact probes. RESULTS: A calibration curve based on artifact-free data was determined for a population of 26 individuals. For an SpO2 range of approximately 83% to 100% and discarding short-term errors, a root mean square error of 1.15% was found with an upper 99% one-sided confidence limit of 1.65%. Under normoxic conditions, a decrease in ambient temperature from 23 to 7 degrees C resulted in a calibration error of 0.1% (+/-1.3%, 99% confidence interval) based on measurements for 3 subjects. PPG signal strengths varied strongly among individuals from about 0.9 * 10 to 4.6 * 10 for the infrared wavelength. CONCLUSIONS: For healthy adults, the results present strong evidence that camera-based contactless pulse oximetry is fundamentally feasible because long-term (eg, 10 minutes) error stemming from variation among individuals expressed as A*rms is significantly lower (<1.65%) than that required by the International Organization for Standardization standard (<4%) with the notion that short-term errors should be added. A first illustration of such errors has been provided with A**rms = 2.54% for 40 individuals, including 6 with dark skin. Low signal strength and subject motion present critical challenges that will have to be addressed to make camera-based pulse oximetry practically feasible. PMID- 27258082 TI - Achieving an Accurate Surface Profile of a Photonic Crystal for Near-Unity Solar Absorption in a Super Thin-Film Architecture. AB - In this work, a teepee-like photonic crystal (PC) structure on crystalline silicon (c-Si) is experimentally demonstrated, which fulfills two critical criteria in solar energy harvesting by (i) its Gaussian-type gradient-index profile for excellent antireflection and (ii) near-orthogonal energy flow and vortex-like field concentration via the parallel-to-interface refraction effect inside the structure for enhanced light trapping. For the PC structure on 500-MUm thick c-Si, the average reflection is only ~0.7% for lambda = 400-1000 nm. For the same structure on a much thinner c-Si ( t = 10 MUm), the absorption is near unity (A ~ 99%) for visible wavelengths, while the absorption in the weakly absorbing range (lambda ~ 1000 nm) is significantly increased to 79%, comparing to only 6% absorption for a 10-MUm-thick planar c-Si. In addition, the average absorption (~94.7%) of the PC structure on 10 MUm c-Si for lambda = 400-1000 nm is only ~3.8% less than the average absorption (~98.5%) of the PC structure on 500 MUm c-Si, while the equivalent silicon solid content is reduced by 50 times. Furthermore, the angular dependence measurements show that the high absorption is sustained over a wide angle range (thetainc = 0-60 degrees ) for teepee-like PC structure on both 500 and 10-MUm-thick c-Si. PMID- 27258083 TI - Correction: The Role of Nature and Nurture for Individual Differences in Primary Emotional Systems: Evidence from a Twin Study. AB - [This corrects the article DOI: 10.1371/journal.pone.0151405.]. PMID- 27258084 TI - Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies. AB - Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin alphaIIbbetaIII to investigate their therapeutic potential as a cardiovascular safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID- 27258085 TI - Pre-operative and post-operative psychiatric manifestations in patients with supratentorial meningiomas. AB - OBJECTIVES: In the present study, we have tried to delineate the nature of psychiatric abnormalities caused by supratentorial meningiomas and the effect of surgery on them. We have tried to find the patient and tumor characters influencing the psychiatric abnormalities and their post-operative outcome. MATERIALS AND METHODS: This is a prospective study conducted on patients with supratentorial meningiomas, admitted and operated in neurosurgery department, Nizam's Institute of Medical Sciences, India, from July 2006 to July 2009. We have included fifty-seven patients aged between 15 and 65 years with a clinico radiological diagnosis of supratentorial meningioma in our study. We later confirmed the diagnosis by histopathological examination of the tumor. We have evaluated the patients for psychiatric manifestations before and after surgery and also analyzed the various clinical and radiological factors influencing the psychiatric status. RESULTS: We have enrolled 57 patients into the study. Frontal group had 22 patients (38.6%), parietal group had 10 patients (17.5%), temporal group had 10 patients (17.5%), occipital group had 6 patients (10.5%), and suprasellar group had 9 patients (15.8%). Twenty patients (35.1%) presented with psychiatric symptoms. The frequency of psychiatric symptoms was highest in the temporal group (60%) followed by the frontal group (45.5%). Frontal convexity meningiomas presented predominantly with depression, basifrontal and sphenoid wing meningiomas presented with mania or depressive symptoms, Suprasellar lesions and temporal convexity lesions presented with organic delusional disorder. Basifrontal meningiomas also caused organic personality disorders. The frequency of psychiatric symptoms was much higher in meningiomas with volume greater than 35cc compared to the smaller ones, in the frontal group. None of the patients developed new psychiatric symptoms after surgery. Among the twenty patients with psychiatric symptoms, 3 (15%) didnot improve, 8 (40%) improved partly and 9 (45%) improved completely. CONCLUSIONS: Meningiomas, although extra-axial, cause significant psychiatric symptoms up to 35.1%. Frontal and temporal group of meningiomas have the highest frequency of psychiatric symptoms. The frequency of psychiatric symptoms was significantly higher in meningiomas with volume greater than 35cc compared to the smaller ones, in the frontal group. Surgical excision of meningiomas ameliorates the psychiatric symptoms, either completely or partly, in the majority of the patients. PMID- 27258086 TI - Knee Joint Loads and Surrounding Muscle Forces during Stair Ascent in Patients with Total Knee Replacement. AB - Total knee replacement (TKR) is commonly used to correct end-stage knee osteoarthritis. Unfortunately, difficulty with stair climbing often persists and prolongs the challenges of TKR patents. Complete understanding of loading at the knee is of great interest in order to aid patient populations, implant manufacturers, rehabilitation, and future healthcare research. Musculoskeletal modeling and simulation approximates joint loading and corresponding muscle forces during a movement. The purpose of this study was to determine if knee joint loadings following TKR are recovered to the level of healthy individuals, and determine the differences in muscle forces causing those loadings. Data from five healthy and five TKR patients were selected for musculoskeletal simulation. Variables of interest included knee joint reaction forces (JRF) and the corresponding muscle forces. A paired samples t-test was used to detect differences between groups for each variable of interest (p<0.05). No differences were observed for peak joint compressive forces between groups. Some muscle force compensatory strategies appear to be present in both the loading and push-off phases. Evidence from knee extension moment and muscle forces during the loading response phase indicates the presence of deficits in TKR in quadriceps muscle force production during stair ascent. This result combined with greater flexor muscle forces resulted in similar compressive JRF during loading response between groups. PMID- 27258087 TI - Effect of Inhaled beta2-Agonist on Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease. AB - The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FENO50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FENO50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD). Likewise, it is not known whether changes in airway calibre in COPD patients alter flow-independent parameters describing pulmonary nitric oxide exchange, such as the maximal flux of nitric oxide (NO) from the proximal airway compartment (J'awNO) and the distal airway/alveolar concentration of NO (CANO). We recruited 24 patients with COPD and performed FENO analysis at multiple expiratory flows before and after treatment with inhaled beta2-agonist bronchodilator therapy. For the 21 patients analysed, FENO50 rose from 17.1 (1.4) ppb (geometric mean (geometric SD)) at baseline, to 19.3 (1.3) ppb after bronchodilator therapy, an increase of 2.2 ppb (95% CI, 0.7-3.6; P = 0.005). There were non-significant changes in flow-independent NO parameters. The change in FENO50 correlated positively with the change in J'awNO (rs = 0.67, P < 0.001; rs = 0.62, P = 0.002 before and after correction for axial back-diffusion respectively) following bronchodilation. Inhaled bronchodilator therapy can increase exhaled nitric oxide measurements in COPD. The standardisation of inhaled bronchodilator therapy before FENO analysis in COPD patients should therefore be considered in both research and clinical settings. PMID- 27258088 TI - Large Salt Dust Storms Follow a 30-Year Rainfall Cycle in the Mar Chiquita Lake (Cordoba, Argentina). AB - Starting in 2006, a new source of intense salt dust storms developed in Mar Chiquita (Cordoba, Argentina), the largest saline lake in South America. Storms originate from vast mudflats left by a 30-year expansion-retreat cycle of the lake due to changes in the regional rainfall regime. The annual frequency of salt dust storms correlated with the size of the salt mudflats. Events were restricted to the coldest months, and reached up to 800 km from the source. Occurrence of dust storms was associated with specific surface colors and textures easily identifiable in satellite images. High-emission surfaces were characterized by the presence of sodium sulfate hydrous/anhydrous crystals (mirabilite and thenardite), and a superficial and variable water table, which may result in the periodic development of a characteristic "fluffy" surface derived from salt precipitation-dissolution processes. HYSPLIT model simulation estimates a deposition maximum near the sources (of about 2.5 kg/ha/yr), and a decreasing trend from the emission area outwards, except for the relative secondary maximum modeled over the mountain ranges in southern Bolivia and northern Argentina due to an orographic effect. The 2009 total deposition of salt dust generated in Mar Chiquita was estimated at 6.5 million tons. PMID- 27258089 TI - Beta Peak Frequencies at Rest Correlate with Endogenous GABA+/Cr Concentrations in Sensorimotor Cortex Areas. AB - Neuronal oscillatory activity in the beta band (15-30 Hz) is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy) and beta oscillations (measured by magnetoencephalography) at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex. PMID- 27258090 TI - Phenol Derivatives as Coupling Partners with Alkylsilicates in Photoredox/Nickel Dual Catalysis. AB - Photoredox/nickel dual catalysis via single electron transmetalation allows coupling of Csp(3)-Csp(2) hybridized centers under mild conditions. A procedure for the coupling of electron-deficient aryl triflates, -tosylates, and -mesylates with alkylbis(catecholato)silicates is presented. This method represents the first example of the use of phenol derivatives as electrophilic coupling partners in photoredox/nickel dual catalysis. PMID- 27258091 TI - Assessment of Levels of Ultraviolet A Light Protection in Automobile Windshields and Side Windows. AB - IMPORTANCE: Ultraviolet A (UV-A) light is associated with the risks of cataract and skin cancer. OBJECTIVE: To assess the level of UV-A light protection in the front windshields and side windows of automobiles. DESIGN: In this cross sectional study, 29 automobiles from 15 automobile manufacturers were analyzed. The outside ambient UV-A radiation, along with UV-A radiation behind the front windshield and behind the driver's side window of all automobiles, was measured. The years of the automobiles ranged from 1990 to 2014, with an average year of 2010. The automobile dealerships were located in Los Angeles, California. MAIN OUTCOMES AND MEASURES: Amount of UV-A blockage from windshields and side windows. The average percentage of front-windshield UV-A blockage was 96% (range, 95%-98% [95% CI, 95.7%-96.3%]) and was higher than the average percentage of side-window blockage, which was 71% (range, 44%-96% [95% CI, 66.4%-75.6%]). The difference between these average percentages is 25% (95% CI, 21%-30% [P < .001]). A high level of side-window UV-A blockage (>90%) was found in 4 of 29 automobiles (13.8%). CONCLUSIONS AND RELEVANCE: The level of front-windshield UV-A protection was consistently high among automobiles. The level of side-window UV-A protection was lower and highly variable. These results may in part explain the reported increased rates of cataract in left eyes and left-sided facial skin cancer. Automakers may wish to consider increasing the degree of UV-A protection in the side windows of automobiles. PMID- 27258092 TI - Clear Plaque Mutants of Lactococcal Phage TP901-1. AB - We report a method for obtaining turbid plaques of the lactococcal bacteriophage TP901-1 and its derivative TP901-BC1034. We have further used the method to isolate clear plaque mutants of this phage. Analysis of 8 such mutants that were unable to lysogenize the host included whole genome resequencing. Four of the mutants had different mutations in structural genes with no relation to the genetic switch. However all 8 mutants had a mutation in the cI repressor gene region. Three of these were located in the promoter and Shine-Dalgarno sequences and five in the N-terminal part of the encoded CI protein involved in the DNA binding. The conclusion is that cI is the only gene involved in clear plaque formation i.e. the CI protein is the determining factor for the lysogenic pathway and its maintenance in the lactococcal phage TP901-1. PMID- 27258093 TI - Analysis of Risk Alleles and Complement Activation Levels in Familial and Non Familial Age-Related Macular Degeneration. AB - AIMS: Age-related macular degeneration (AMD) is a multifactorial disease, in which complement-mediated inflammation plays a pivotal role. A positive family history is an important risk factor for developing AMD. Certain lifestyle factors are shown to be significantly associated with AMD in non-familial cases, but not in familial cases. This study aimed to investigate whether the contribution of common genetic variants and complement activation levels differs between familial and sporadic cases with AMD. METHODS AND RESULTS: 1216 AMD patients (281 familial and 935 sporadic) and 1043 controls (143 unaffected members with a family history of AMD and 900 unrelated controls without a family history of AMD) were included in this study. Ophthalmic examinations were performed, and lifestyle and family history were documented with a questionnaire. Nine single nucleotide polymorphisms (SNPs) known to be associated with AMD were genotyped, and serum concentrations of complement components C3 and C3d were measured. Associations were assessed in familial and sporadic individuals. The association with risk alleles of the age-related maculopathy susceptibility 2 (ARMS2) gene was significantly stronger in sporadic AMD patients compared to familial cases (p = 0.017 for all AMD stages and p = 0.003 for advanced AMD, respectively). ARMS2 risk alleles had the largest effect in sporadic cases but were not significantly associated with AMD in densely affected families. The C3d/C3 ratio was a significant risk factor for AMD in sporadic cases and may also be associated with familial cases. In patients with a densely affected family this effect was particularly strong with ORs of 5.37 and 4.99 for all AMD and advanced AMD respectively. CONCLUSION: This study suggests that in familial AMD patients, the common genetic risk variant in ARMS2 is less important compared to sporadic AMD. In contrast, factors leading to increased complement activation appear to play a larger role in patients with a positive family history compared to sporadic patients. A better understanding of the different contributions of risk factors in familial compared to non-familial AMD will aid the development of reliable prediction models for AMD, and may provide individuals with more accurate information regarding their individual risk for AMD. This information is especially important for individuals who have a positive family history for AMD. PMID- 27258094 TI - Socioeconomic Gradient in Childhood Obesity and Hypertension: A Multilevel Population-Based Study in a Chinese Community. AB - BACKGROUND: This study aims to assess evidence for any socioeconomic gradients in childhood obesity and hypertension in a population-representative sample in Hong Kong, China. METHODS: The data of a stratified random sampled growth survey collected in 2005-2006 was matched with a population by-census. Obesity was defined using the International Obesity Task Force standard and hypertension was defined using the Hong Kong norm table. Family socioeconomic status (SES) was measured by maternal education level. Neighbourhood SES was measured by median household income of the neighbourhood. Multilevel Poisson regression models with robust standard error were used to test the association. Body mass indices of children's parents were included as potential confounders. Intra school/neighbourhood correlations were adjusted using random factors. RESULTS: Totally 14842 children (age 6-19 years) included in the analysis, in which 16.6% of them were overweight or obese. Children whose mother only completed secondary school or below had higher risk of childhood obesity (RR 1.41, 95% CI 1.13-1.76, p = 0.003) and hypertension (RR 1.18, 95% CI 1.01-1.36, p = 0.03). Meanwhile, children in the lowest neighbourhood SES group had higher risk of childhood underweight (RR 1.61, 95% CI 1.04-2.49, p = 0.03), overweight (RR 1.35, 95% CI 1.05-1.72, p = 0.02), and obesity (RR 2.07, 95% CI 1.11-3.88, p = 0.02). CONCLUSIONS: Socioeconomic gradient in childhood obesity and hypertension existed in Hong Kong, one of the most developed cities in China. These results have implications for policymakers and public health experts and highlight the need to monitor trends in other parts of China. PMID- 27258095 TI - Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis. AB - RATIONALE: Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation. OBJECTIVES: To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself. METHODS: A total of 2,639 sweat chloride measurements were obtained in 1,761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modeling. MEASUREMENTS AND MAIN RESULTS: Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%), and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H2 = 0; 95% confidence interval, 0.0-0.35). For an individual with CF, variation in sweat chloride was primarily caused by variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%). CONCLUSIONS: Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non CFTR variation is caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker for assessing response to therapies directed at mutant CFTR. PMID- 27258097 TI - Application of the removal of pollutants from textile industry wastewater in constructed wetlands using fuzzy logic. AB - There are more than a hundred textile industries in Turkey that discharge large quantities of dye-rich wastewater, resulting in water pollution. Such effluents must be treated to meet discharge limits imposed by the Water Framework Directive in Turkey. Industrial treatment facilities must be required to monitor operations, keep them cost-effective, prevent operational faults, discharge-limit infringements, and water pollution. This paper proposes the treatment of actual textile wastewater by vertical flow constructed wetland (VFCW) systems operation and monitoring effluent wastewater quality using fuzzy logic with a graphical user interface. The treatment performance of VFCW is investigated in terms of chemical oxygen demand and ammonium nitrogen (NH4-N) content, color, and pH parameters during a 75-day period of operation. A computer program was developed with a fuzzy logic system (a decision- making tool) to graphically present (via a status analysis chart) the quality of treated textile effluent in relation to the Turkish Water Pollution Control Regulation. Fuzzy logic is used in the evaluation of data obtained from the VFCW systems and for notification of critical states exceeding the discharge limits. This creates a warning chart that reports any errors encountered in a reactor during the collection of any sample to the concerned party. PMID- 27258096 TI - Women's Preferences for Treatment of Perinatal Depression and Anxiety: A Discrete Choice Experiment. AB - Perinatal depression and anxiety (PNDA) are an international healthcare priority, associated with significant short- and long-term problems for women, their children and families. Effective treatment is available but uptake is suboptimal: some women go untreated whilst others choose treatments without strong evidence of efficacy. Better understanding of women's preferences for treatment is needed to facilitate uptake of effective treatment. To address this issue, a discrete choice experiment (DCE) was administered to 217 pregnant or postnatal women in Australia, who were recruited through an online research company and had similar sociodemographic characteristics to Australian data for perinatal women. The DCE investigated preferences regarding cost, treatment type, availability of childcare, modality and efficacy. Data were analysed using logit-based models accounting for preference and scale heterogeneity. Predicted probability analysis was used to explore relative attribute importance and policy change scenarios, including how these differed by women's sociodemographic characteristics. Cost and treatment type had the greatest impact on choice, such that a policy of subsidising effective treatments was predicted to double their uptake compared with the base case. There were differences in predicted uptake associated with certain sociodemographic characteristics: for example, women with higher educational attainment were more likely to choose effective treatment. The findings suggest policy directions for decision makers whose goal is to reduce the burden of PNDA on women, their children and families. PMID- 27258098 TI - Red Blood Cells from Individuals with Abdominal Obesity or Metabolic Abnormalities Exhibit Less Deformability upon Entering a Constriction. AB - Abdominal obesity and metabolic syndrome (MS) are multifactorial conditions associated with increased risk of cardiovascular disease and type II diabetes mellitus. Previous work has demonstrated that the hemorheological profile is altered in patients with abdominal obesity and MS, as evidenced for example by increased whole blood viscosity. To date, however, no studies have examined red blood cell (RBC) deformability of blood from individuals with obesity or metabolic abnormalities under typical physiological flow conditions. In this study, we pumped RBCs through a constriction in a microfluidic device and used high speed video to visualize and track the mechanical behavior of ~8,000 RBCs obtained from either healthy individuals (n = 5) or obese participants with metabolic abnormalities (OMA) (n = 4). We demonstrate that the OMA+ cells stretched on average about 25% less than the healthy controls. Furthermore, we examined the effects of ingesting a high-fat meal on RBC mechanical dynamics, and found that the postprandial period has only a weak effect on the stretching dynamics exhibited by OMA+ cells. The results suggest that chronic rigidification of RBCs plays a key role in the increased blood pressure and increased whole blood viscosity observed in OMA individuals and was independent of an acute response triggered by consumption of a high-fat meal. PMID- 27258099 TI - A D-Shaped Bileaflet Bioprosthesis which Replicates Physiological Left Ventricular Flow Patterns. AB - Prior studies have shown that in a healthy heart, there exist a large asymmetric vortex structure that aids in establishing a steady flow field in the left ventricle. However, the implantation of existing artificial heart valves at the mitral position is found to have a negative effect on this physiological flow pattern. In light of this, a novel D-shaped bileaflet porcine bioprosthesis (GD valve) has been designed based on the native geometry mitral valve, with the hypothesis that biomimicry in valve design can restore physiological left ventricle flow patterns after valve implantation. An in-vitro experiment using two dimensional particle velocimetry imaging was carried out to determine the hemodynamic performance of the new bileaflet design and then compared to that of the well-established St. Jude Epic valve which functioned as a control in the experiment. Although both valves were found to have similar Reynolds shear stress and Turbulent Kinetic Energy levels, the novel D-shape valve was found to have lower turbulence intensity and greater mean kinetic energy conservation. PMID- 27258101 TI - Correction: Proteogenomic Characterization of Monocyclic Aromatic Hydrocarbon Degradation Pathways in the Aniline-degrading Bacterium Burkholderia sp. K24. AB - [This corrects the article DOI: 10.1371/journal.pone.0154233.]. PMID- 27258100 TI - "I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients. AB - Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life. PMID- 27258118 TI - Intraocular Tumor Associated With Visual Loss in a Young Woman. PMID- 27258119 TI - Prediction of Pathological Stage in Patients with Prostate Cancer: A Neuro-Fuzzy Model. AB - The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer. However, not every patient will return abnormal results in all tests. This significantly influences the capacity to effectively predict the stage of prostate cancer. Herein we have developed a neuro-fuzzy computational intelligence model for classifying and predicting the likelihood of a patient having Organ-Confined Disease (OCD) or Extra-Prostatic Disease (ED) using a prostate cancer patient dataset obtained from The Cancer Genome Atlas (TCGA) Research Network. The system input consisted of the following variables: Primary and Secondary Gleason biopsy patterns, PSA levels, age at diagnosis, and clinical T stage. The performance of the neuro-fuzzy system was compared to other computational intelligence based approaches, namely the Artificial Neural Network, Fuzzy C-Means, Support Vector Machine, the Naive Bayes classifiers, and also the AJCC pTNM Staging Nomogram which is commonly used by clinicians. A comparison of the optimal Receiver Operating Characteristic (ROC) points that were identified using these approaches, revealed that the neuro-fuzzy system, at its optimal point, returns the largest Area Under the ROC Curve (AUC), with a low number of false positives (FPR = 0.274, TPR = 0.789, AUC = 0.812). The proposed approach is also an improvement over the AJCC pTNM Staging Nomogram (FPR = 0.032, TPR = 0.197, AUC = 0.582). PMID- 27258120 TI - Extracellular Matrix (ECM) Multilayer Membrane as a Sustained Releasing Growth Factor Delivery System for rhTGF-beta3 in Articular Cartilage Repair. AB - Recombinant human transforming growth factor beta-3 (rhTGF-beta3) is a key regulator of chondrogenesis in stem cells and cartilage formation. We have developed a novel drug delivery system that continuously releases rhTGF-beta3 using a multilayered extracellular matrix (ECM) membrane. We hypothesize that the sustained release of rhTGF-beta3 could activate stem cells and result in enhanced repair of cartilage defects. The properties and efficacy of the ECM multilayer based delivery system (EMLDS) are investigated using rhTGF-beta3 as a candidate drug. The bioactivity of the released rhTGF-beta3 was evaluated through chondrogenic differentiation of mesenchymal stem cells (MSCs) using western blot and circular dichroism (CD) analyses in vitro. The cartilage reparability was evaluated through implanting EMLDS with endogenous and exogenous MSC in both in vivo and ex vivo models, respectively. In the results, the sustained release of rhTGF-beta3 was clearly observed over a prolonged period of time in vitro and the released rhTGF-beta3 maintained its structural stability and biological activity. Successful cartilage repair was also demonstrated when rabbit MSCs were treated with rhTGF-beta3-loaded EMLDS ((+) rhTGF-beta3 EMLDS) in an in vivo model and when rabbit chondrocytes and MSCs were treated in ex vivo models. Therefore, the multilayer ECM membrane could be a useful drug delivery system for cartilage repair. PMID- 27258121 TI - Multiple Patterns of Regulation and Overexpression of a Ribonuclease-Like Pathogenesis-Related Protein Gene, OsPR10a, Conferring Disease Resistance in Rice and Arabidopsis. AB - An abundant 17 kDa RNase, encoded by OsPR10a (also known as PBZ1), was purified from Pi-starved rice suspension-cultured cells. Biochemical analysis showed that the range of optimal temperature for its RNase activity was 40-70 degrees C and the optimum pH was 5.0. Disulfide bond formation and divalent metal ion Mg2+ were required for the RNase activity. The expression of OsPR10a::GUS in transgenic rice was induced upon phosphate (Pi) starvation, wounding, infection by the pathogen Xanthomonas oryzae pv. oryzae (Xoo), leaf senescence, anther, style, the style-ovary junction, germinating embryo and shoot. We also provide first evidence in whole-plant system, demonstrated that OsPR10a-overexpressing in rice and Arabidopsis conferred significant level of enhanced resistance to infection by the pathogen Xoo and Xanthomona campestris pv. campestris (Xcc), respectively. Transgenic rice and Arabidopsis overexpressing OsPR10a significantly increased the length of primary root under phosphate deficiency (-Pi) condition. These results showed that OsPR10a might play multiple roles in phosphate recycling in phosphate-starved cells and senescing leaves, and could improve resistance to pathogen infection and/or against chewing insect pests. It is possible that Pi acquisition or homeostasis is associated with plant disease resistance. Our findings suggest that gene regulation of OsPR10a could act as a good model system to unravel the mechanisms behind the correlation between Pi starvation and plant pathogen interactions, and also provides a potential application in crops disease resistance. PMID- 27258123 TI - Association Between Heart Rate Variability Measures and Blood Glucose Levels: Implications for Noninvasive Glucose Monitoring for Diabetes. AB - BACKGROUND: Diabetes mellitus (DM) is a global metabolic epidemic associated with numerous adverse complications. Invasive finger prick tests or invasive monitors are currently the most common means of monitoring and controlling blood glucose levels (BGLs). Heart rate variability (HRV) is a noninvasive measure of the autonomic nervous system, and its dynamic physiological nature may provide an alternative means of blood glucose monitoring. However, the relationship between BGL and HRV parameters remains relatively unknown. MATERIALS AND METHODS: Thirty two participants with diabetes (39.97 +/- 17.21 years of age) and 31 without diabetes (27.87 +/- 10.55 years of age) participated in the current study. Fasting preceded a 10-min three-lead electrocardiogram (ECG), which was followed by a finger prick blood glucose assessment. Following this, a regular meal was consumed, and 30 min after ingestion, a second postprandial 10-min ECG was obtained, and blood glucose assessment was conducted. RESULTS: Low-frequency (LF) power, high-frequency (HF) power, and total power (TP) of HRV were negatively associated with BGL in participants with DM. Additionally, the ratio of LF to HF was positively correlated with BGL. Duration of DM was also associated with multiple HRV parameters, with negative associations to both LF and HF parameters as well as TP. CONCLUSIONS: This study demonstrates links between specific HRV variables and BGL. In the future the dynamic nature of HRV could provide a unique and real-time method for monitoring BGL, for continuous noninvasive prediction and/or management of DM. PMID- 27258122 TI - Association of HbA1c to BOLUS Scores Among Youths with Type 1 Diabetes. AB - BACKGROUND: Frequency of mealtime insulin bolusing (BOLUS) is a promising new objective assessment of adherence in youths with type 1 diabetes (T1D). As further confirmation of the validity of BOLUS, we compare the associations of glycated hemoglobin (HbA1c) values of T1D youths with the original scoring of BOLUS and two alternative scoring procedures: mean mealtime boluses within a 2-h meal window (2h-BOLUS) and total daily frequency of boluses (TOTAL-BOLUS). In addition, we assess HbA1c associations of these three procedures, including interaction terms for mealtime boluses plus correction boluses. SUBJECTS AND METHODS: Blood glucose meter data, insulin pump records, and HbA1c levels were collected from a combined clinical and research database for a random sample of 100 youths (mean age, 12.7 +/- 4.6 years). Youths' pump records were scored using the published methodology and alternative procedures for evaluating insulin use. RESULTS: Youths' BOLUS, TOTAL-BOLUS, and mealtime boluses within a 2-h meal window (2h-BOLUS) scores are independently associated with youths' HbA1c level; all measures demonstrated stronger associations with youths' HbA1c than did frequency of glucose monitoring. The strongest association was between youths' BOLUS score and their HbA1c level. In multiple regression analyses, youths' BOLUS score better explains the variations in HbA1c levels than either youths' 2h-BOLUS or TOTAL-BOLUS scores. When combined with BOLUS in the same relationships, 2h BOLUS and TOTAL-BOLUS were not found to have statistically significant coefficients. None of the bivariate relationships of HbA1c and interaction terms of mealtime and correction boluses was significant. CONCLUSIONS: The original method for calculating BOLUS appears superior to alternative scoring methods in its association with youths' HbA1c levels. PMID- 27258124 TI - Cross-Border Cholera Outbreaks in Sub-Saharan Africa, the Mystery behind the Silent Illness: What Needs to Be Done? AB - INTRODUCTION: Cross-border cholera outbreaks are a major public health problem in Sub-Saharan Africa contributing to the high annual reported cholera cases and deaths. These outbreaks affect all categories of people and are challenging to prevent and control. This article describes lessons learnt during the cross border cholera outbreak control in Eastern and Southern Africa sub-regions using the case of Uganda-DRC and Malawi-Mozambique borders and makes recommendations for future outbreak prevention and control. MATERIALS AND METHODS: We reviewed weekly surveillance data, outbreak response reports and documented experiences on the management of the most recent cross-border cholera outbreaks in Eastern and Southern Africa sub-regions, namely in Uganda and Malawi respectively. Uganda Democratic Republic of Congo and Malawi-Mozambique borders were selected because the countries sharing these borders reported high cholera disease burden to WHO. RESULTS: A total of 603 cross-border cholera cases with 5 deaths were recorded in Malawi and Uganda in 2015. Uganda recorded 118 cases with 2 deaths and CFR of 1.7%. The under-fives and school going children were the most affected age groups contributing 24.2% and 36.4% of all patients seen along Malawi-Mozambique and Uganda-DRC borders, respectively. These outbreaks lasted for over 3 months and spread to new areas leading to 60 cases with 3 deaths, CRF of 5%, and 102 cases 0 deaths in Malawi and Uganda, respectively. Factors contributing to these outbreaks were: poor sanitation and hygiene, use of contaminated water, floods and rampant cross-border movements. The outbreak control efforts mainly involved unilateral measures implemented by only one of the affected countries. CONCLUSIONS: Cross-border cholera outbreaks contribute to the high annual reported cholera burden in Sub-Saharan Africa yet they remain silent, marginalized and poorly identified by cholera actors (governments and international agencies). The under-fives and the school going children were the most affected age groups. To successfully prevent and control these outbreaks, guidelines and strategies should be reviewed to assign clear roles and responsibilities to cholera actors on collaboration, prevention, detection, monitoring and control of these epidemics. PMID- 27258125 TI - Structural and functional integration between dorsal and ventral language streams as revealed by blunt dissection and direct electrical stimulation. AB - The most accepted framework of language processing includes a dorsal phonological and a ventral semantic pathway, connecting a wide network of distributed cortical hubs. However, the cortico-subcortical connectivity and the reciprocal anatomical relationships of this dual-stream system are not completely clarified. We performed an original blunt microdissection of 10 hemispheres with the exposition of locoregional short fibers and six long-range fascicles involved in language elaboration. Special attention was addressed to the analysis of termination sites and anatomical relationships between long- and short-range fascicles. We correlated these anatomical findings with a topographical analysis of 93 functional responses located at the terminal sites of the language bundles, collected by direct electrical stimulation in 108 right-handers. The locations of phonological and semantic paraphasias, verbal apraxia, speech arrest, pure anomia, and alexia were statistically analyzed, and the respective barycenters were computed in the MNI space. We found that terminations of main language bundles and functional responses have a wider distribution in respect to the classical definition of language territories. Our analysis showed that dorsal and ventral streams have a similar anatomical layer organization. These pathways are parallel and relatively segregated over their subcortical course while their terminal fibers are strictly overlapped at the cortical level. Finally, the anatomical features of the U-fibers suggested a role of locoregional integration between the phonological, semantic, and executive subnetworks of language, in particular within the inferoventral frontal lobe and the temporoparietal junction, which revealed to be the main criss-cross regions between the dorsal and ventral pathways. Hum Brain Mapp 37:3858-3872, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27258126 TI - A microcosm investigation of fe (iron) removal using macrophytes of ramsar lake: A phytoremediation approach. AB - The present study deals with the microcosm study of Fe (Iron) phytoremediation using Eichhornia crassipes, Lemna minor, Pistia stratiotes and Salvinia cucullata species collected from the Loktak Lake, a Ramsar Site which exists in north eastern India (an Indo-Burma hotspot region). Efficiency of these four macrophytes was compared using different Fe concentrations of 1 mg L(-1), 3 mg L( 1) and 5 mg L(-1) for 4 days, 8 days and 12 days, respectively. E. crassipes was the most efficient macrophyte whereas L. minor was the least efficient. E. crassipes removed the highest percentage of Fe, i.e. 89% from 1 mg L(-1), 81.3% from 3 mg L(-1) and 73.2% from 5 mg L(-1) in 12-day experiment. PMID- 27258136 TI - Hepatic and renal toxicological evaluations of an industrial ovotoxic chemical, 4 vinylcyclohexene diepoxide, in both sexes of Wistar rats. AB - 4-Vinylcyclohexene diepoxide (VCD) is an industrial occupational health hazard chemical because it induces ovotoxicity in rodents. The current study investigated the impacts of VCD on selected hepatic and renal markers of oxidative stress and inflammation in both sexes of Wistar rats. Thus, male and female rats were randomly distributed into four groups of ten rats per group, and dosed orally with VCD for 28days. The control male and female groups of rats received corn oil only, while each of the three remaining groups of both sexes of rats received VCD (100, 250 and 500mg/kg BW) respectively. Thereafter, biomarkers of hepatic and renal oxidative damage, inflammation and immunohistochemical expressions of iNOS, COX-2, caspase-9 and caspase-3 were evaluated. The results revealed that VCD increased markers of liver and kidney functions, oxidative damage and inflammation, and disrupted the antioxidant homeostasis of the rats (p<0.05). Lastly, VCD enhanced the immunohistochemical expressions of iNOS, COX 2, caspase-9 and caspase-3 in the liver of the rats. Thus, our data imply that VCD induced toxicity in the liver and kidney of rats via the combined impacts of oxidative damage and inflammation. PMID- 27258137 TI - The herbicide glyphosate is a weak inhibitor of acetylcholinesterase in rats. AB - The current work evaluated the inhibitory potency of the herbicide glyphosate (GLP) on acetylcholinesterase (AChE) activity in male and female rat tissues. The AChE activity in brain was higher (p<0.05) than those observed in kidney (females: 2.2-fold; males: 1.9-fold), liver (females: 6-fold; males: 6.9-fold) and plasma (females: 14.7-fold; males: 25.3-fold). Enzyme activities were higher in presence of 10mM GLP compared to those measured at an equimolar concentration of the potent AChE inhibitor dichlorvos (DDVP). Moreover, IC50s for GLP resulted between 6*10(4)- and 6.8*10(5)-fold higher than those observed for DDVP. In conclusion, GLP is a weak inhibitor of AChE in rats. PMID- 27258138 TI - Apelin-13 in blood pressure regulation and cardiovascular disease. AB - PURPOSE OF REVIEW: Despite extensive pharmacological treatment, hypertension and heart failure still pose as high health and economic burden. Thus, novel therapeutic approaches are needed to promote more effective treatment of hypertension and cardiovascular disease. In this review we summarized recent evidence supporting the therapeutic potential of apelin-13, a recently discovered endogenous ligand for the G-protein coupled receptor APJ. RECENT FINDINGS: Systemic administration of apelin-13 or its posttranslationally modified form, pyroglutamate apelin-13, exert vasodilatory and antihypertensive effects. Yet, central application of apelin increases blood pressure and its systemic effects may be compromised in the presence of endothelial dysfunction. In addition, positive inotropic effects by exogenous apelin in the normal and failing heart, as well as cardioprotective effects after myocardial infarction, strongly suggest its therapeutic potential in preventing and treating heart failure and consequences of myocardial ischemia. However, therapeutic use of apelin is limited primarily by its short half-life and parenteral administration, and significant effort has been directed to the development of novel agonists, delivery methods, and improving the efficacy of agonists at APJ. SUMMARY: The apelin/APJ axis may represent a new target for the development of novel therapeutic approaches for the treatment of hypertension and cardiovascular disease. PMID- 27258139 TI - Biodegradable Oxamide-Phenylene-Based Mesoporous Organosilica Nanoparticles with Unprecedented Drug Payloads for Delivery in Cells. AB - We describe biodegradable mesoporous hybrid nanoparticles (NPs) in the presence of proteins and their applications for drug delivery. We synthesized oxamide phenylene-based mesoporous organosilica nanoparticles (MON) in the absence of a silica source which had remarkably high organic content and high surface areas. Oxamide functions provided biodegradability in the presence of trypsin model proteins. MON displayed exceptionally high payloads of hydrophilic and hydrophobic drugs (up to 84 wt %), and a unique zero premature leakage without the pore capping, unlike mesoporous silica. MON were biocompatible and internalized into cancer cells for drug delivery. PMID- 27258140 TI - On-resin N-terminal peptoid degradation: Toward mild sequencing conditions. AB - A novel approach to sequentially degrade peptoid N-terminal N (substituted)glycine residues on the solid-phase using very mild conditions is reported. This method relies on the treatment of resin-bound, bromoacetylated peptoids with silver perchlorate in THF, leading to an intramolecular cyclization reaction to liberate the terminal residue as a N-substituted morpholine-2,5 dione, resulting in a truncated peptoid upon hydrolysis and a silver bromide byproduct. Side-chain functional group tolerance is explored and reaction kinetics are determined. In a series of pentapeptoids possessing variable, non nucleophilic side-chains at the second position (R(2) ), we demonstrate that sequential N-terminal degradation of the first two residues proceeds in 87% and 74% conversions on average, respectively. We further demonstrate that the degradation reaction is selective for peptoids, and represents substantial progress toward a mild, iterative sequencing method for peptoid oligomers. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 726-736, 2016. PMID- 27258141 TI - Differences of Longitudinal Chromatic Aberration (LCA) between Eyes with Intraocular Lenses from Different Manufacturers. AB - Several researchers have studied the longitudinal chromatic aberration (LCA) of eyes implanted with an intraocular lens (IOL). We investigated the LCA of eyes implanted with yellow-colored IOLs from three different manufacturers: Alcon Inc., HOYA Corp., and AMO Inc. The number of subjects was 11, 16, and 16, respectively. The LCA of eyes implanted with SN60WF and SN60AT (Alcon Inc.), and with XY-1 (HOYA Corp.), was the same as that of phakic eyes. The LCA of eyes with ZCB00V (AMO Inc.) was smaller than that of phakic eyes. The LCA of eyes implanted with Alcon's and HOYA's IOLs, but not the LCA of eyes implanted with AMO's IOLs, was positively correlated with the powers of the IOLs. We also performed simulations to verify the impacts of LCA on visual performance for 4-mm pupil diameter; the simulations were a polychromatic modulation transfer function (MTF) and a visual Strehl ratio computed on the basis of an optical transfer function (VSOTF). We concluded that the differences between the LCA of different manufacturers do not affect visual performances when some extent of higher-order aberration (HOA) exists. The smaller HOA of AMO IOLs may enhance visual performance. PMID- 27258142 TI - Whole Genome DNA Sequence Analysis of Salmonella subspecies enterica serotype Tennessee obtained from related peanut butter foodborne outbreaks. AB - Establishing an association between possible food sources and clinical isolates requires discriminating the suspected pathogen from an environmental background, and distinguishing it from other closely-related foodborne pathogens. We used whole genome sequencing (WGS) to Salmonella subspecies enterica serotype Tennessee (S. Tennessee) to describe genomic diversity across the serovar as well as among and within outbreak clades of strains associated with contaminated peanut butter. We analyzed 71 isolates of S. Tennessee from disparate food, environmental, and clinical sources and 2 other closely-related Salmonella serovars as outgroups (S. Kentucky and S. Cubana), which were also shot-gun sequenced. A whole genome single nucleotide polymorphism (SNP) analysis was performed using a maximum likelihood approach to infer phylogenetic relationships. Several monophyletic lineages of S. Tennessee with limited SNP variability were identified that recapitulated several food contamination events. S. Tennessee clades were separated from outgroup salmonellae by more than sixteen thousand SNPs. Intra-serovar diversity of S. Tennessee was small compared to the chosen outgroups (1,153 SNPs), suggesting recent divergence of some S. Tennessee clades. Analysis of all 1,153 SNPs structuring an S. Tennessee peanut butter outbreak cluster revealed that isolates from several food, plant, and clinical isolates were very closely related, as they had only a few SNP differences between them. SNP-based cluster analyses linked specific food sources to several clinical S. Tennessee strains isolated in separate contamination events. Environmental and clinical isolates had very similar whole genome sequences; no markers were found that could be used to discriminate between these sources. Finally, we identified SNPs within variable S. Tennessee genes that may be useful markers for the development of rapid surveillance and typing methods, potentially aiding in traceback efforts during future outbreaks. Using WGS can delimit contamination sources for foodborne illnesses across multiple outbreaks and reveal otherwise undetected DNA sequence differences essential to the tracing of bacterial pathogens as they emerge. PMID- 27258144 TI - Expressing Anger Is More Dangerous than Feeling Angry when Driving. AB - Anger is an emotion that drivers often feel and express while driving, and it is believed by researchers to be an important cause of dangerous driving behavior. In this study, the relationships between driving trait anger, driving anger expression, and dangerous driving behaviors were analyzed. The Driving Anger Scale (DAS) was used to measure driving trait anger, whereas the Driving Anger Expression (DAX) Inventory was used to measure expressions of driving anger. A sample of 38 drivers completed the DAS, DAX, and a driving simulation session on a simulator where their driving behaviors were recorded. Correlation analysis showed that the higher scores on the DAS were associated with longer durations of speeding in the simulator. The more participants expressed their anger in verbal and physical ways, the more likely they were to crash the virtual vehicle during the simulation. Regression analyses illustrated the same pattern. The findings suggest that, although trait anger is related to speeding, the passive expression of anger is the real factor underling traffic accidents. This study extends findings about the predictive effects of self-report scales of driving behaviors to behaviors recorded on a simulator. Thus, if in traffic safety propaganda, guiding drivers to use positive ways to cope with driving anger is recommended by our findings. PMID- 27258145 TI - The Effects of Cattle Manure and Garlic Rotation on Soil under Continuous Cropping of Watermelon (Citrullus lanatus L.). AB - Continuous cropping of watermelon (Citrullus lanatus L.) can lead to reduced yield and quality. We aimed to determine the effects of cattle manure addition and rotation with green garlic to improve yield and reduce disease incidence in watermelon and to examine the effects on the biological and chemical characteristics of the soil. Field experiments were performed during 2012-2014 on land previously under two years of continuous watermelon cropping in northwest China. We examined three treatment combinations: watermelon and garlic rotation, cattle manure application before watermelon planting, and combined cattle manure addition and crop rotation. Watermelon monoculture was retained as a control. Watermelon yield was significantly higher and disease incidence was lower in the treatments than the control. The populations of soil bacteria and actinomycetes and the bacteria/fungi ratio increased significantly and soil enzyme activities were generally enhanced under treatments. Available nutrients and soil organic matter contents were much higher under experimental treatments than the control. Results suggest both cattle manure application and garlic rotation can ameliorate the negative effects of continuous cropping. The combined treatment of cattle manure addition and green garlic rotation was optimal to increase yield, reduce disease incidence and enhance soil quality. PMID- 27258143 TI - The Alpha-1A Adrenergic Receptor in the Rabbit Heart. AB - The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 MUg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 MUg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse. PMID- 27258146 TI - Effects of four different cooking methods on some quality characteristics of low fat Inegol meatball enriched with flaxseed flour. AB - The present study is concerned with the effects of four different cooking methods (grill, oven, pan and ohmic cooking) on physicochemical parameters (cooking yield moisture retention, fat retention, color, texture), fatty acid composition and sensory characteristics of low fat Turkish traditional Inegol meatball. Flaxseed flour was used as a fat substitute in the production of meatballs. Meatball proximate composition was affected by the cooking methods mainly as a consequence of the weight losses. The highest cooking yield was found in samples cooked in the oven. Flaxseed flour contains high amount of alpha-linolenic acid and ohmic cooking seems to be the best cooking method in terms of retaining this fatty acid in meatballs enriched with flaxseed flour. However ohmic cooked meatball samples had a brighter surface color and harder texture in comparison with meatball samples cooked via traditional methods. There was no significant difference between the sensory evaluation scores of meatballs. PMID- 27258147 TI - Identification of New Mutations at the PCNA Subunit Interface that Block Translesion Synthesis. AB - Proliferating cell nuclear antigen (PCNA) plays an essential role in DNA replication and repair by interacting with a large number of proteins involved in these processes. Two amino acid substitutions in PCNA, both located at the subunit interface, have previously been shown to block translesion synthesis (TLS), a pathway for bypassing DNA damage during replication. To better understand the role of the subunit interface in TLS, we used random mutagenesis to generate a set of 33 PCNA mutants with substitutions at the subunit interface. We assayed the full set of mutants for viability and sensitivity to ultraviolet (UV) radiation. We then selected a subset of 17 mutants and measured their rates of cell growth, spontaneous mutagenesis, and UV-induced mutagenesis. All except three of these 17 mutants were partially or completely defective in induced mutagenesis, which indicates a partial or complete loss of TLS. These results demonstrate that the integrity of the subunit interface of PCNA is essential for efficient TLS and that even conservative substitutions have the potential to disrupt this process. PMID- 27258149 TI - Consequences for Piglet Performance of Group Housing Lactating Sows at One, Two, or Three Weeks Post-Farrowing. AB - Housing lactating sows with piglets in a multi-suckling pen from around 14 days post-farrowing is common practice in Swedish organic piglet production. However, nursing-suckling interaction is less frequent in multi-suckling pens than in individual farrowing pens, thus affecting piglet performance, e.g., piglet growth. Moreover, piglet mortality is higher in systems using multi-suckling pens. Three management routines whereby lactating sows with piglets were moved from individual farrowing pens to multi-suckling pens at one, two, or three weeks post-farrowing were compared in terms of nursing-suckling interaction and piglet performance. Correlations between nursing-suckling interaction, piglet performance, and piglet mortality were also examined. In total, 43 Yorkshire sows with piglets were included in the study. Nursing-suckling interaction and all piglet performance parameters except piglet mortality did not differ between management routines. Piglet mortality in the individual farrowing pens did not differ between management routines, but piglet mortality in the multi-suckling pen was lower (P<0.05) when piglets were group housed at three weeks compared with one week post-farrowing. Overall piglet mortality was positively correlated with mortality in the multi-suckling pen for piglets group housed at one week (r = 0.61: P<0.05) and at two weeks post-farrowing (r = 0.62: P<0.05) but not for piglets group housed at three weeks post-farrowing. In conclusion, overall piglet mortality could be reduced if sows and piglets are group housed at three weeks post-farrowing and piglet survival the first week post-farrowing is improved. PMID- 27258150 TI - Organocatalytic One-Pot Asymmetric Synthesis of Thiolated Spiro-gamma-lactam Oxindoles Bearing Three Stereocenters. AB - The first asymmetric synthesis of spiro-gamma-lactam oxindoles bearing three stereocenters is reported. One-pot thiol-Michael/Mannich/lactamization reactions promoted by a recyclable fluorous bifunctional cinchona alkaloid/thiourea organocatalyst afford products in moderate to good yields with up to 95% ee and 6:1 dr. PMID- 27258151 TI - Statistical Analyses of Hydrophobic Interactions: A Mini-Review. AB - This review focuses on the striking recent progress in solving for hydrophobic interactions between small inert molecules. We discuss several new understandings. First, the inverse temperature phenomenology of hydrophobic interactions, i.e., strengthening of hydrophobic bonds with increasing temperature, is decisively exhibited by hydrophobic interactions between atomic scale hard sphere solutes in water. Second, inclusion of attractive interactions associated with atomic-size hydrophobic reference cases leads to substantial, nontrivial corrections to reference results for purely repulsive solutes. Hydrophobic bonds are weakened by adding solute dispersion forces to treatment of reference cases. The classic statistical mechanical theory for those corrections is not accurate in this application, but molecular quasi-chemical theory shows promise. Finally, because of the masking roles of excluded volume and attractive interactions, comparisons that do not discriminate the different possibilities face an interpretive danger. PMID- 27258148 TI - Overexpression of PIN1 Enhances Cancer Growth and Aggressiveness with Cyclin D1 Induction in EBV-Associated Nasopharyngeal Carcinoma. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a peculiar Epstein Barr virus (EBV) associated malignancy that is prevalent in South-East Asia. Peptidyl-prolyl cis trans isomerase NIMA-interacting 1 (PIN1) isomerizes specific phosphorylated amino acid residues, which makes it an important regulator in cell survival and apoptosis. In this study, we investigated the contribution made by PIN1 in NPC tumorigenesis and PIN1's potential role as a therapeutic target. METHODS: The expression of PIN1 was examined in a panel of NPC cell lines, xenografts and primary tumors. The functional roles of PIN1 in NPC cells were elucidated by the knockdown and overexpression of PIN1 in in vitro and in vivo nude mice models by siRNA and lenti-viral transfection, respectively. The antitumor effects of the PIN1 inhibitor Juglone in NPC cells were also evaluated. RESULTS: We revealed the consistent overexpression of PIN1 in almost all EBV-associated NPC cell lines, xenografts and primary tumors. PIN1 suppression was capable of inhibiting cyclin D1 expression and activating caspase-3 in NPC cells. It positively regulated NPC cell proliferation, colony formation and anchorage-independent growth. The inhibition of PIN1 suppressed tumor growth in vitro and in vivo. CONCLUSIONS: This study demonstrates the oncogenic role of PIN1 in NPC tumorigenesis, and shows that its overexpression can enhance tumor cell growth via the upregulation of cyclinD1. Our findings inform the development of novel treatments targeting PIN1 for NPC patients. PMID- 27258152 TI - Mesenchymal to Epithelial Transition Induced by Reprogramming Factors Attenuates the Malignancy of Cancer Cells. AB - Epithelial to mesenchymal transition (EMT) is a biological process of metastatic cancer. However, an effective anticancer therapy that directly targets the EMT program has not yet been discovered. Recent studies have indicated that mesenchymal to epithelial transition (MET), the reverse phenomenon of EMT, is observed in fibroblasts during the generation of induced pluripotent stem cells. In the present study, we investigated the effects of reprogramming factors (RFs) on squamous cell carcinoma (SCC) cells. RFs-introduced cancer cells (RICs) demonstrated the enhanced epithelial characteristics in morphology with altered expression of mRNA and microRNAs. The motility and invasive activities of RICs in vitro were significantly reduced. Furthermore, xenografts of RICs exhibited no lymph node metastasis, whereas metastasis was detected in parental SCC-inoculated mice. Thus, we concluded that RICs regained epithelial properties through MET and showed reduced cancer malignancy in vitro and in vivo. Therefore, the understanding of the MET process in cancer cells by introduction of RFs may lead to the designing of a novel anticancer strategy. PMID- 27258153 TI - Correction: Prognostic Value of Lactate and Central Venous Oxygen Saturation after Early Resuscitation in Sepsis Patients. AB - [This corrects the article DOI: 10.1371/journal.pone.0153305.]. PMID- 27258154 TI - Safety and efficiency of dexmedetomidine as adjuvant to local anesthetics. AB - PURPOSE OF REVIEW: To review the current knowledge of dexmedetomidine as an additive drug to local anesthetics in peripheral and neuraxial regional anesthesia. RECENT FINDINGS: Recent studies show a perineural mode of action of dexmedetomidine. Pharmacodynamic characteristics of peripheral and neuraxial regional anesthetic techniques are optimized by the addition of dexmedetomidine to long-acting local anesthetics. Bradycardia and sedation are the main systemic side-effects of dexmedetomidine for regional anesthesia purposes. A dose of approximately 100 MUg dexmedetomidine for peripheral techniques may represent the optimal balance between optimization of block characteristics and side-effects. Doses between 3 and 10 MUg are described to be sufficient for spinal administration. SUMMARY: Dexmedetomidine has a potency to ameliorate pharmacodynamic characteristics of peripheral and neuraxial regional anesthetic techniques and is therefore currently the most promising additive drug in regional anesthesia. Future scientific efforts should focus on dose finding studies for particular regional anesthetic techniques. Approval of dexmedetomidine for regional anesthetic indications should be the final target. PMID- 27258155 TI - Which patients benefit from regional anaesthesia? AB - PURPOSE OF REVIEW: The aim of the review is to examine the possible benefit of regional anaesthesia in four areas of perioperative care. These are: the relationship between anaesthesia and cancer recurrence; the effects of regional anaesthesia in orthopaedic surgery; its use in people with obstructive sleep apnoea syndrome; and its potential for preventing chronic postsurgical pain. RECENT FINDINGS: There are a number of studies of different designs attempting to shed light on these topics. These range from animal work, through observational studies including analyses of administrative databases, to randomized controlled trials, and systematic reviews. One methodological difficulty within clinical investigations is to fully distinguish patients who have received regional anaesthesia from those who have received general anaesthesia, as many receive regional anaesthesia with sedation and this is not always separately noted, nor the degree of sedation recorded. This continues to make interpretation difficult. SUMMARY: There is at present little unequivocal, high-quality evidence to confirm clear superiority of regional anaesthesia over general anaesthesia for any of the conditions described in this article. Perhaps as important as the choice of technique is the practitioner's skill and attention to detail; in addition, the major contributor to perioperative risk remains the patient and his/her pre existing condition. PMID- 27258156 TI - Correction: Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice. AB - [This corrects the article DOI: 10.1371/journal.pone.0153298.]. PMID- 27258157 TI - Targeting Human alpha-Lactalbumin Gene Insertion into the Goat beta-Lactoglobulin Locus by TALEN-Mediated Homologous Recombination. AB - Special value of goat milk in human nutrition and well being is associated with medical problems of food allergies which are caused by milk proteins such as beta lactoglobulin (BLG). Here, we employed transcription activator-like effector nuclease (TALEN)-assisted homologous recombination in goat fibroblasts to introduce human alpha-lactalbumin (hLA) genes into goat BLG locus. TALEN-mediated targeting enabled isolation of colonies with mono- and bi-allelic transgene integration in up to 10.1% and 1.1%, respectively, after selection. Specifically, BLG mRNA levels were gradually decreasing in both mo- and bi-allelic goat mammary epithelial cells (GMECs) while hLA demonstrated expression in GMECs in vitro. Gene-targeted fibroblast cells were efficiently used in somatic cell nuclear transfer, resulting in production of hLA knock-in goats directing down-regulated BLG expression and abundant hLA secretion in animal milk. Our findings provide valuable background for animal milk optimization and expedited development for agriculture and biomedicine. PMID- 27258158 TI - Investigation of Bias in Continuous Medical Image Label Fusion. AB - Image labeling is essential for analyzing morphometric features in medical imaging data. Labels can be obtained by either human interaction or automated segmentation algorithms, both of which suffer from errors. The Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm for both discrete-valued and continuous-valued labels has been proposed to find the consensus fusion while simultaneously estimating rater performance. In this paper, we first show that the previously reported continuous STAPLE in which bias and variance are used to represent rater performance yields a maximum likelihood solution in which bias is indeterminate. We then analyze the major cause of the deficiency and evaluate two classes of auxiliary bias estimation processes, one that estimates the bias as part of the algorithm initialization and the other that uses a maximum a posteriori criterion with a priori probabilities on the rater bias. We compare the efficacy of six methods, three variants from each class, in simulations and through empirical human rater experiments. We comment on their properties, identify deficient methods, and propose effective methods as solution. PMID- 27258159 TI - The Critical Role Played by the Catalytic Moiety in the Early-Time Photodynamics of Hydrogen-Generating Bimetallic Photocatalysts. AB - The effect of the catalytic moiety on the early-time photodynamics of Ru/M (M=Pt or Pd) bimetallic photocatalysts is studied by ultrafast transient absorption spectroscopy. In comparison to the Ru/Pd photocatalyst described earlier, the Ru/Pt analogue shows complex excited-state dynamics with three distinct kinetic components ranging from sub-ps to 10(2) ps, requiring a more sophisticated photophysical model than that developed earlier for the Ru/Pd complex. In the Pu/Pt photocatalyst, an additional lower-lying excited state is proposed to quench the hot higher-lying triplet metal-to-ligand charge-transfer states. Furthermore, a strong excitation wavelength dependence on the population of excited states is observed for both the Ru/Pt and Ru/Pd complexes, indicating a non-equilibrated distribution even on the 10(2) ps timescale. These insights shed light on the significant impact of the catalytic moiety on the fundamental early-time photophysics of Ru-based photocatalysts. PMID- 27258161 TI - Detection and Identification of Leachables in Vaccine from Plastic Packaging Materials Using UPLC-QTOF MS with Self-Built Polymer Additives Library. AB - The direct contact of plastic parts with the medical products raises the possibility that plastic-related contaminants (leachables) may be present in the finished medical product. The leachable components from plastic materials may impact the safety and efficacy of the final medical product, so identification and determination of the leachables are essential for the safety assessment of medical products. A method to identify main leachables-polymer additives in medical products was developed by ultraperformance liquid chromatography quadrupole time-of-flight-mass spectrometry (UPLC-QTOF MS) and a self-built library. The library contains 174 additives and the information on their names, formulas, structures, retention times, fragments, classifications, origin, and corresponding MS(E) and MSMS spectra. The reliability of the construction process of the library was guaranteed by the system stability and suitability test. Identification parameters of library application, such as mass error, retention times, fragments, and isotope pattern, were evaluated. Leachables in real vaccine and the intermediates were identified using automatic library searching. In vaccine, the peak m/z 239.0887 that could not be assigned by the library was identified as dimethyl 2-hydroxy-1,3-cyclohexanedicarboxylate using a series of elucidation tools. As a result, the concentrations of leachables in vaccine and the intermediates ranged from 0.85 to 21.91 MUg/L. PMID- 27258160 TI - CRISPR-Mediated Triple Knockout of SLAMF1, SLAMF5 and SLAMF6 Supports Positive Signaling Roles in NKT Cell Development. AB - The SLAM family receptors contribute to diverse aspects of lymphocyte biology and signal via the small adaptor molecule SAP. Mutations affecting SAP lead to X linked lymphoproliferative syndrome Type 1, a severe immunodysregulation characterized by fulminant mononucleosis, dysgammaglobulinemia, and lymphoproliferation/lymphomas. Patients and mice having mutations affecting SAP also lack germinal centers due to a defect in T:B cell interactions and are devoid of invariant NKT (iNKT) cells. However, which and how SLAM family members contribute to these phenotypes remains uncertain. Three SLAM family members: SLAMF1, SLAMF5 and SLAMF6, are highly expressed on T follicular helper cells and germinal center B cells. SLAMF1 and SLAMF6 are also implicated in iNKT development. Although individual receptor knockout mice have limited iNKT and germinal center phenotypes compared to SAP knockout mice, the generation of multi receptor knockout mice has been challenging, due to the genomic linkage of the genes encoding SLAM family members. Here, we used Cas9/CRISPR-based mutagenesis to generate mutations simultaneously in Slamf1, Slamf5 and Slamf6. Genetic disruption of all three receptors in triple-knockout mice (TKO) did not grossly affect conventional T or B cell development and led to mild defects in germinal center formation post-immunization. However, the TKO worsened defects in iNKT cells development seen in SLAMF6 single gene-targeted mice, supporting data on positive signaling and potential redundancy between these receptors. PMID- 27258163 TI - Efficient Arsenic Methylation and Volatilization Mediated by a Novel Bacterium from an Arsenic-Contaminated Paddy Soil. AB - Microbial arsenic (As) methylation and volatilization are important processes controlling the As biogeochemical cycle in paddy soils. To further understand these processes, we isolated a novel bacterial strain, SM-1, from an As contaminated paddy soil. SM-1 showed strong As methylation and volatilization abilities, converting almost all arsenite (10 MUM) to dimethylarsenate and trimethylarsenic oxide in the medium and trimethylarsine gas into the headspace within 24 h, with trimethylarsine accounting for nearly half of the total As. On the basis of the 16S rRNA sequence, strain SM-1 represents a new species in a new genus within the family Cytophagaceae. Strain SM-1 is abundant in the paddy soil and inoculation of SM-1 greatly enhanced As methylation and volatilization in the soil. An arsenite methyltransferase gene (ArarsM) was cloned from SM-1. When expressed in Escherichia coli, ArArsM conferred the As methylation and volatilization abilities to E. coli and increased its resistance to arsenite. The high As methylation and volatilization abilities of SM-1 are likely attributed to an efficient ArArsM enzyme coupled with low arsenite efflux. These results suggest that strain SM-1 plays an important role in As methylation and volatilization in the paddy soil and has a great potential for As bioremediation. PMID- 27258164 TI - Catalyst-Free Insertion of Sulfoxonium Ylides into Aryl Thiols. A Direct Preparation of beta-Keto Thioethers. AB - Insertion of sulfoxonium ylides into the S-H bond of aryl thiols without the need for a catalyst is demonstrated, furnishing beta-keto thioethers in excellent yield in most cases. The method overcomes traditional syntheses that employ metal catalysts in combination with diazo compounds or toxic and hard-prepared haloketones. The experimental setup consists of mixing the reagents in acetonitrile at room temperature. Additional experimental as well as kinetic isotopic effect studies give some insight into the mechanism of this reaction. PMID- 27258165 TI - Challenges in the Heterologous Production of Antibiotics in Streptomyces. AB - The fast growing genome databases provide us with a large number of so far unknown secondary metabolite biosynthetic gene clusters. A key method to study these gene clusters is their heterologous expression in an engineered host strain. Gene clusters derived from actinomycetes are usually expressed in a Streptomyces host strain to identify and investigate the corresponding compounds. However, heterologous expression is often accompanied with some challenges affecting the production rates of secondary metabolites. The first step is therefore the selection of a suitable expression vector and host strain. Once production has been established, there are several possibilities to improve compound yields either by media screens, by overexpression of regulatory or transport genes or by introduction of constitutive or inducible promoters. A surely important, but hitherto little studied factor is also the regulation of a heterologously expressed gene cluster by its host strain. This review gives a short overview on the chances and challenges provided by heterologous production of secondary metabolites in Streptomyces. PMID- 27258166 TI - Familial expansile osteolysis: An Australian case report of a Paget's Disease Mimic. AB - We report a case of familial expansile osteolysis (FEO) with multimodality imaging findings and histopathological correlation in a 42-year-old man presenting to a South Australian Emergency Department. FEO is a unique metabolic bone condition that is similar in some respects to Paget's disease but distinct enough in its clinical, radiological and histological findings to be classified as a separate disease process. It is inherited in an autosomal dominant pattern and typified by increased osteoclast activity, medullary expansion, and hearing and dental problems. These changes can lead to significant morbidity with individuals affected suffering from bone pain and pathological fractures. To the best of the authors' knowledge, there are no reported cases in the literature documenting this disease in Australia. PMID- 27258162 TI - Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review. AB - Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first-degree relative (FDR) increases the CRC risk 2-fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is <50% and is lower in persons under the age of 50 years. A provider's recommendation, multiple affected relatives, and family encouragement facilitate screening; insufficient collection of FH, low knowledge of guidelines, and poor family communication are important barriers. Effective interventions incorporate strategies for overcoming barriers, but these have not been broadly tested in clinical settings. Four strategies for reducing CRC in persons with familial risk are suggested: 1) improving the collection and utilization of the FH of cancer, 2) establishing a consensus for screening guidelines by FH, 3) enhancing provider-patient knowledge of guidelines and communication about CRC risk, and 4) encouraging survivors to promote screening within their families and partnering with existing screening programs to expand their reach to high-risk groups. Cancer 2016. (c) 2016 American Cancer Society. Cancer 2016;122:2633-2645. (c) 2016 American Cancer Society. PMID- 27258167 TI - Should all mucosal head and neck cancer patients be treated in high volume centres, or can some be appropriately triaged to local centres for treatment. PMID- 27258168 TI - Are we training the next generation of proficient radiation oncologists, or just better examination candidates? PMID- 27258169 TI - Hypofractionated versus conventionally fractionated radiotherapy for ductal carcinoma in situ (DCIS) of the breast. AB - INTRODUCTION: Hypofractionated radiotherapy (RT) in the setting of early invasive breast cancer has been shown to have similar local control rates and cosmetic outcomes as conventionally fractionated RT. This study compares ipsilateral recurrence rates between hypofractionated and conventional RT, with and without a boost. The effect of hypofractionated RT and chest wall separation (CWS) on cosmetic outcome was also assessed. METHODS: All patients with ductal carcinoma in situ (DCIS) treated between 1998 and 2012 across two sites of a single cancer institution were retrospectively studied. Patients were analysed according to those receiving conventional RT (<=2 Gy per fraction) and those receiving hypofractionated RT (>2 Gy per fraction), as well as the presence or absence of a tumour bed boost. Data were collected through electronic medical records and local cancer registry. Cosmetic outcome was scored by physicians on a four-point scale during clinical follow-up appointments. RESULTS: One hundred and ninety seven patients were treated for DCIS during the study period. One hundred and forty-one were treated with conventional RT, and 56 with hypofractionated RT. After a median follow up of 4.4 years, there were 12 ipsilateral recurrences, of which seven were invasive disease and five DCIS. Ten recurrences occurred in patients who received conventional RT (7.1% recurrence rate) and two in those who received hypofractionated RT (3.6% recurrence rate) (P = 0.48). Cosmetic outcomes were not significantly different between conventional and hypofractionated RT (P = 0.06). CONCLUSIONS: Hypofractionation represents a suitable alternative for treating DCIS in the absence of randomised data. PMID- 27258171 TI - Diketopyrrolopyrrole-based Conjugated Polymers Bearing Branched Oligo(Ethylene Glycol) Side Chains for Photovoltaic Devices. AB - Conjugated polymers are essential for solution-processable organic opto electronic devices. In contrast to the great efforts on developing new conjugated polymer backbones, research on developing side chains is rare. Herein, we report branched oligo(ethylene glycol) (OEG) as side chains of conjugated polymers. Compared with typical alkyl side chains, branched OEG side chains endowed the resulting conjugated polymers with a smaller pi-pi stacking distance, higher hole mobility, smaller optical band gap, higher dielectric constant, and larger surface energy. Moreover, the conjugated polymers with branched OEG side chains exhibited outstanding photovoltaic performance in polymer solar cells. A power conversion efficiency of 5.37 % with near-infrared photoresponse was demonstrated and the device performance could be insensitive to the active layer thickness. PMID- 27258172 TI - An electrochemical DNA biosensor based on nitrogen-doped graphene/Au nanoparticles for human multidrug resistance gene detection. AB - Multidrug resistance (MDR) has become a major obstacle to the adequate treatment of cancer patients; thus, there is an urgent need for exploring new strategies for early diagnosis of MDR in clinic. Here, we report a novel electrochemical biosensor based on nitrogen-doped graphene nanosheets functionalized with Au nanoparticles (N-G/Au) for sensitive and selective DNA detection. The highly conductive nanocomposite layer was characterized by using scanning and transmission electron microscopy, X-ray photoelectron spectroscopy, and cyclic voltammetry. DNA with thiol groups at the 5' end was immobilized on the N-G/Au surface via the strong Au-S bond. Differential pulse voltammetry was applied to monitor the target DNA hybridization event using methylene blue as an electrochemical indicator. Under optimal conditions, the biosensor could detect target DNA down to 3.12*10(-15)M with a linear range from 1.0*10(-14) to 1.0*10( 7)M, showing high sensitivity. Further, the sensing strategy was successfully used for detecting MDR1 DNA in real clinical samples. These results will aid in developing a new portable detection system for MDR that will allow effective diagnosis in the early stages of related cancer. PMID- 27258173 TI - Electrocatalytic determination of nitrite based on straw cellulose/molybdenum sulfide nanocomposite. AB - Cellulose is the most abundant, renewable, biodegradable natural polymer resource on earth, which can be a good substrate for catalysis. In this work, straw cellulose has been oxidized through 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation, and then a TEMPO oxidized straw cellulose/molybdenum sulfide (TOSC-MoS2) composite has been synthesized via a hydrothermal method. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) analysis confirm that TOSC and MoS2 have successfully composited. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images show the TOSC as a carbon nanotube-like structure and edged MoS2 grows on the TOSC substrate. The TOSC-MoS2 modified glassy carbon electrode (GCE) is used as a simple and non-enzymatic electrochemical sensor. Cyclic Voltammetry (CV) result shows TOSC-MoS2 has excellent electrocatalytic activity for the oxidation of nitrite. The amperometric response result indicates the TOSC-MoS2 modified GCE can be used to determine nitrite concentration in wide linear ranges of 6.0-3140 and 3140-4200uM with a detection limit of 2.0uM. The proposed sensor has good anti-interference property. Real sample analysis and the electrocatalytic mechanism have also been presented. PMID- 27258174 TI - The Anesthetic Implications of Aqueous Drainage Devices and Glaucoma: A Report of a Patient Undergoing Urgent Prone Cervical Decompression and Fusion. AB - The pathophysiology of glaucoma and perioperative visual loss is similar. A patient with glaucoma may be at increased risk of perioperative visual loss. For both, goals of management include optimizing ocular perfusion pressure and oxygen delivery. One treatment for refractory glaucoma is an aqueous drainage device; however, there is no published literature on the anesthetic management of patients with these devices. We present the case of a patient with recalcitrant glaucoma treated with an Ahmed Glaucoma Valve who underwent urgent prone surgery. Anesthetic implications of aqueous drainage devices and glaucoma are discussed, and recommendations are made. PMID- 27258175 TI - Leveraging the Preoperative Clinic to Engage Older Patients in Shared Decision Making About Complex Surgery: An Illustrative Case. AB - The decision to pursue surgery is often complicated in older adults. A multidisciplinary, shared approach to decision-making may improve communication between patients and their providers and facilitate complex risk assessment. We describe a case of an older adult presenting for complex surgery in which the preoperative anesthesia clinic visit was used to facilitate involvement of the geriatrics service. This multidisciplinary approach allowed for re-evaluation and reiteration of risks and benefits, in-depth discussion of the patient's values and goals, and recommendations for care teams downstream in the patient's surgical pathway to ensure treatment consistent with patient goals and clinical recommendations. PMID- 27258176 TI - A Rare Case of Transverse Sinus Venous Thrombosis Simulating Postdural Puncture Headache After Cervical Epidural Injection. AB - Postdural puncture headache (PDPH) is a feared complication related to epidural steroid injections. We report a unique case in which all subjective and objective findings indicated the diagnosis of PDPH. However, the patient failed appropriate conservative and interventional management. Therapeutic failure prompted further investigation to establish the correct diagnosis of cerebral venous sinus thrombosis. Cerebral venous sinus thrombosis is a rare, difficult to diagnose, but potentially lethal disorder with nonspecific and variable clinical presentations, including headache and focal neurological deficits. Performing magnetic resonance imaging and magnetic resonance venogram should be considered early, especially in patients who fail to respond to standard interventions for PDPH. PMID- 27258177 TI - Management of a Patient With Tetralogy of Fallot, Congenital Diaphragmatic Hernia, and Complete Left Lung Agenesis. AB - We describe the rare case of an infant with congenital diaphragmatic hernia, unilateral lung agenesis, and unpalliated single-ventricle physiology. Infants with congenital diaphragmatic hernia and parallel circulation are at risk for maldistribution of systemic and pulmonary blood flow. Optimal perioperative management should include an assessment of the ratio of pulmonary to systemic blood flow (Qp:Qs). Traditionally, arterial and systemic venous oxygen (SvO2) saturations are needed to calculate Qp:Qs. However, in this case, SvO2 measurement was not feasible. On the basis of a previously described relationship, we used 2-site near-infrared spectroscopy to calculate a near infrared spectroscopy-derived SvO2, which was then used to estimate Qp:Qs and guide goal-directed interventions. PMID- 27258178 TI - Continuous Suprascapular Nerve Block With a Perineural Catheter for Reverse Shoulder Arthroplasty Rescue Analgesia in a Patient With Severe Chronic Obstructive Pulmonary Disease. AB - Reverse open shoulder arthroplasty requires a comprehensive analgesic plan involving regional anesthesia. The commonly performed interscalene brachial plexus blockade confers a high likelihood of diaphragmatic paralysis via phrenic nerve palsy, making this option riskier in patients with limited pulmonary reserve. Continuous blockade of the suprascapular nerve, a more distal branch of the C5 and C6 nerve roots, may be a viable alternative. We report a successful case of the use of a suprascapular nerve block with continuous programmed intermittent bolus perineural analgesia in a patient with severe chronic obstructive pulmonary disease who underwent reverse open shoulder arthroplasty. PMID- 27258179 TI - Otocephaly Complex: Case Report, Literature Review, and Ethical Considerations. AB - Otocephaly complex is a rare and usually lethal syndrome characterized by a set of malformations consisting of microstomia, mandibular hypoplasia/agnathia, and ventromedial malposition of the ears. Those cases that have been diagnosed prenatally have used an ex utero intrapartum treatment procedure to establish a definitive airway. However, prenatal diagnosis continues to be challenging, primarily because of poor diagnostic sensitivity associated with ultrasonography. We present a case of a newborn with an unanticipated otocephaly complex requiring emergent airway management. In this report, we discuss the medical and ethical issues related to the care of a newborn with this frequently fatal condition. PMID- 27258180 TI - Successful Treatment of Refractory Hypoxemia Secondary to Disseminated Histoplasmosis Using Extracorporeal Membrane Oxygenation Support. AB - Refractory hypoxemia secondary to acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membraneoxygenation (ECMO) is an accepted strategy for treating refractory hypoxemia in patients with ARDS but is relatively contraindicated in the setting of systemic infections. We present a case of successful ECMO use in a host with refractory hypoxemia secondary to disseminated histoplasmosis with fungemia and discuss our management approach to this difficult patient. PMID- 27258181 TI - A Web-Based Operating Room Management Educational Tool. AB - In 2010, our department instituted a nonclinical, administrative rotation in operating room management for anesthesiology residents. Subsequently, we mandated the rotation for all senior anesthesiology residents in 2013. In 2014, under the auspices of the American Society of Anesthesiologists, we developed a web-based module covering the basics of finance, accounting, and operating room management. A multiple-choice test was given to residents at the beginning and end of the rotation, and we compared the mean scores between residents who took the traditional course and residents who took the web-based module. We found no significant difference between the groups of residents, suggesting that the web based module is as effective as traditional didactics. PMID- 27258182 TI - Dysfunctional miRNA-Mediated Regulation in Chromophobe Renal Cell Carcinoma. AB - Past research on pathogenesis of a complex disease suggests that differentially expressed message RNAs (mRNAs) can be noted as biomarkers of a disease. However, significant miRNA-mediated regulation change might also be more deep underlying cause of a disease. In this study, a miRNA-mediated regulation module is defined based on GO terms (Gene Ontology terms) from which dysfunctional modules are identified as the suspected cause of a disease. A miRNA-mediated regulation module contains mRNAs annotated to a GO term and MicroRNAs (miRNAs) which regulate the mRNAs. Based on the miRNA-mediated regulation coefficients estimated from the expression profiles of the mRNA and the miRNAs, a SW (single regulation weight) value is then designed to evaluate the miRNA-mediated regulation change of an mRNA, and the modules with significantly differential SW values are thus identified as dysfunctional modules. The approach is applied to Chromophobe renal cell carcinoma and it identifies 70 dysfunctional miRNA-mediated regulation modules from initial 4381 modules. The identified dysfunctional modules are detected to be comprehensive reflection of chromophobe renal cell carcinoma. The proposed approach suggests that accumulated alteration in miRNA-mediated regulation might cause functional alterations, which further cause a disease. Moreover, this approach can also be used to identify diffentially miRNA-mediated regulated mRNAs showing more comprehensive underlying association with a disease than differentially expressed mRNAs. PMID- 27258183 TI - Mechanical Energy Recovery during Walking in Patients with Parkinson Disease. AB - The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD). The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64+/-9 years) with bilateral symptoms (H&Y >=II) if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs). Ten healthy subjects (mean age 62+/-3 years) walked both at their 'preferred' and 'slow' speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM) of hip, knee and ankle joint angles. We also measured kinetic (Wk), potential (Wp), total (WtotCM) energy variations and the energy recovery index (ER). Along with PD progression, we found a significant correlation of WtotCM and Wp with knee ROM and in particular with knee extension in terminal stance phase. Wk and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both Wp and WtotCM. Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait related energetic components. PMID- 27258184 TI - Size-Dependent Catalytic Activity of Palladium Nanoparticles Fabricated in Porous Organic Polymers for Alkene Hydrogenation at Room Temperature. AB - Ultrafine palladium nanoparticles (Pd NPs) with 8 and 3 nm sizes were effectively fabricated in triazine functionalized porous organic polymer (POP) TRIA that was developed by nonaqueous polymerization of 2,4,6-triallyoxy-1,3,5-triazine. The Pd NPs encapsulated POP (Pd-POP) was fully characterized using several techniques. Further studies revealed an excellent capability of Pd-POP for catalytic transfer hydrogenation of alkenes at room temperature with superior catalytic performance and high selectivity of desired products. Highly flammable H2 gas balloon at high pressure and temperature used in conventional hydrogenation reactions was not needed in the present synthetic system. Catalytic activity is strongly dependent on the size of encapsulated Pd NPs in the POP. The Pd-POP catalyst with Pd NPs of 8 nm in diameter exhibited higher catalytic activity for alkene hydrogenation as compared with the Pd-POP catalyst encapsulating 3 nm Pd NPs. Computational studies were undertaken to gain insights into different catalytic activities of these two Pd-POP catalysts. High reusability and stability as well as no Pd leaching of these Pd-POP catalysts make them highly applicable for hydrogenation reactions at room temperature. PMID- 27258185 TI - The role of CTLA-4 and PD-1 in anti-tumor immune response and their potential efficacy against osteosarcoma. AB - Immunotherapy is proved to be a promising therapeutic strategy against human malignancies. Evasion of immune surveillance is considered to be a major factor of malignant progression. Inhibitory receptors, especially CTLA-4 and PD-1, are found to play critical roles in the mediation of anti-tumor immune efficacy. Thus, antibodies targeting these immune checkpoints have emerged as the attractive treatment approaches to those patients with cancer. Osteosarcoma is highly malignant and current treatment remains a challenge, especially for those patients with metastasis. Despite some achievements, the effect of immunotherapy against osteosarcoma is still unsatisfactory. The present review attempts to show the role and mechanism of CTLA-4 and PD-1 in immune response and summarize the recent findings related to the effect of inhibitory receptor antibodies on the immune response against tumors, especially osteosarcoma, and the correlation between PD-1 or/and CTLA-4 expression and outcome of osteosarcoma patients. We further discuss the utilization of the combination therapy against osteosarcoma. PMID- 27258186 TI - The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus. AB - Sirolimus can significantly amplify regulatory T cells (Tregs) in vivo and in vitro, but the specific mechanism of this has not been well documented. The role of regulatory B cells (Bregs) in the Tregs-amplifying effect of Sirolimus was investigated in peripheral blood mononuclear cells (PBMCs) in vitro in this study. The results showed that the percentages of both CD19+CD24+CD38+TGF-beta1+ Bregs and CD19+CD24+CD38+IL-10+ Bregs to B cells were elevated by Sirolimus in PBMCs including B cells. Sirolimus significantly enhances the cytokine production of transforming growth factor-beta1 (TGF-beta1) and interleukin-10 (IL-10) in PBMCs with B cells, and the enhancement significantly decreased in PBMCs without B cells. The percentage of CD4+CD25+Foxp3+ Tregs to T cells was also elevated by Sirolimus in PBMCs including B cells. The elevation of Tregs percentage decreased in PBMCs without B cells and recovered when additional TGF-beta1 and IL-10 were added. The amplification of Tregs by Sirolimus was partially inhibited when either TGF-beta1 or IL-10 was neutralized, and it even disappeared when these two cytokines were both neutralized. These results indicate that Sirolimus can amplify Bregs and Tregs in PBMCs in vitro, and Bregs may be the why Sirolimus amplifies Tregs. PMID- 27258187 TI - Could B7-H4 serve as a target to activate anti-cancer immunity? AB - It has been over 13years since the identification of B7-H4, the co-stimulatory molecule of B7 family members. While B7-H4 mRNA is widely distributed protein expression seems to be limited on tissues. Various cytokines and inflammatory mediators induce the expression of B7-H4. However, the specific regulatory mechanisms of B7-H4 remain to be defined. Recently, it has been shown that B7-H4 executes an inhibitory function in the T-cell response via reduced expansion, cell cycle arrest, decreased cytokine secretion and induced apoptosis of activated T-cells. Furthermore, B7-H4 suppresses the function of antigen presenting cells (APCs) and promotes the proliferation and development of regulatory T-cells (Treg). Moreover, a growing body of literature demonstrates that various cancers express B7-H4 and that the expression levels of B7-H4 correlate with cancer size, histological type, pathologic stage, grade, infiltration, lymph node metastasis, cancer progression, recurrence and death. The over-expression of B7-H4 in cancer may be related to an increased resistance to immune responses. The aim of this review is to supply an overview of the advances in the regulation and function of B7-H4. Additionally, many studies have suggested that B7-H4 is a molecular target for therapeutic intervention in cancer and that targeting B7-H4 may have promising potential for improving the efficacy of immunotherapy for cancer patients. PMID- 27258188 TI - Mechanisms of histone lysine-modifying enzymes: A computational perspective on the role of the protein environment. AB - Epigenetic pathways are involved in a wide range of diseases, including cancer and neurological disorders. Specifically, histone modifying and reading processes are the most broadly studied and are targeted by several licensed drugs. Although there have been significant advances in understanding the mechanistic aspects underlying epigenetic regulation, the development of selective small-molecule inhibitors remains a challenge. Experimentally, it is generally difficult to elucidate the atomistic basis for substrate recognition, as well as the sequence of events involved in binding and the subsequent chemical processes. In this regard, computational modelling is particularly valuable, since it can provide structural features (including transition state structures along with kinetic and thermodynamic parameters) that enable both qualitative and quantitative evaluation of the mechanistic details involved. Here, we summarize knowledge gained from computational modelling studies elucidating the role of the protein environment in histone-lysine modifying and reading mechanisms. We give a perspective on the importance of calculations to aid and advance the understanding of these processes and for the future development of selective inhibitors for epigenetic regulators. PMID- 27258189 TI - A theoretical study of pi-stacking interactions in C-substituted tetrazoles. AB - The pi-stacking effects of benzene ring (Ben) with 1H- and 2H-tetrazole derivatives (1H-TZ-X and 2H-TZ-X) substituted at C5 (where X is Cl, COH, NO, NO2, CN, NH2, OH, OCH3, SH and H) has been investigated by the quantum mechanical calculations at the M06-2X/6-311++G** level. The results indicate the 1H-TZ X||Ben complexes (|| donates pi-stacking interaction) are more stable than 2H-TZ X||Ben while in unstacked forms, 1H-TZ-X is less stable than 2H-TZ-X. All substituents enhance the pi-stacking interaction relative to the unsubstituted ones and enhancement is higher for the electron-withdrawing substituents (EWSs). Also, investigation of the local and direct effect of substituents in stacking interaction showed that all substituents regardless of whether are electron donating or electron withdrawing have an additive effect in pi-stacking interaction. Excellent correlations were found between the binding energies of the complexes and combination of substituent constant terms. The results showed that the electrostatic interaction alone is not responsible for stacking stabilization but charge penetration is important. Furthermore, analysis of aromaticity, AIM, ESP and NPA were investigated to obtain aromaticity index, non bonding interactions, chemical reactivity and polarity (dipole moment), respectively. PMID- 27258190 TI - Transition-Metal-Catalyzed Redox-Neutral and Redox-Green C-H Bond Functionalization. AB - Transition-metal-catalyzed C-H bond functionalization has become one of the most promising strategies to prepare complex molecules from simple precursors. However, the utilization of environmentally unfriendly oxidants in the oxidative C-H bond functionalization reactions reduces their potential applications in organic synthesis. This account describes our recent efforts in the development of a redox-neutral C-H bond functionalization strategy for direct addition of inert C-H bonds to unsaturated double bonds and a redox-green C-H bond functionalization strategy for realization of oxidative C-H functionalization with O2 as the sole oxidant, aiming to circumvent the problems posed by utilizing environmentally unfriendly oxidants. In principle, these redox-neutral and redox green strategies pave the way for establishing new environmentally benign transition-metal-catalyzed C-H bond functionalization strategies. PMID- 27258191 TI - Corrigendum. PMID- 27258192 TI - Mirtazapine: A Drug with Many Palliative Uses #314. PMID- 27258193 TI - Wolf (Canis lupus) Generation Time and Proportion of Current Breeding Females by Age. AB - Information is sparse about aspects of female wolf (Canis lupus) breeding in the wild, including age of first reproduction, mean age of primiparity, generation time, and proportion of each age that breeds in any given year. We studied these subjects in 86 wolves (113 captures) in the Superior National Forest (SNF), Minnesota (MN), during 1972-2013 where wolves were legally protected for most of the period, and in 159 harvested wolves from throughout MN wolf range during 2012 2014. Breeding status of SNF wolves were assessed via nipple measurements, and wolves from throughout MN wolf range, by placental scars. In the SNF, proportions of currently breeding females (those breeding in the year sampled) ranged from 19% at age 2 to 80% at age 5, and from throughout wolf range, from 33% at age 2 to 100% at age 7. Excluding pups and yearlings, only 33% to 36% of SNF females and 58% of females from throughout MN wolf range bred in any given year. Generation time for SNF wolves was 4.3 years and for MN wolf range, 4.7 years. These findings will be useful in modeling wolf population dynamics and in wolf genetic and dog-domestication studies. PMID- 27258194 TI - Suppressing Respiration Effects when Geometric Distortion Is Corrected Dynamically by Phase Labeling for Additional Coordinate Encoding (PLACE) during Functional MRI. AB - Echo planar imaging (EPI) suffers from geometric distortions caused by magnetic field inhomogeneities, which can be time-varying as a result of small amounts of head motion that occur over seconds and minutes during fMRI experiments, also known as "dynamic geometric distortion". Phase Labeling for Additional Coordinate Encoding (PLACE) is a promising technique for geometric distortion correction without reduced temporal resolution and in principle can be used to correct for motion-induced dynamic geometric distortion. PLACE requires at least two EPI images of the same anatomy that are ideally acquired with no variation in the magnetic field inhomogeneities. However, head motion and lung ventilation during the respiratory cycle can cause changes in magnetic field inhomogeneities within the EPI pair used for PLACE. In this work, we exploited dynamic off-resonance in k-space (DORK) and averaging to correct the within EPI pair magnetic field inhomogeneities; and hence proposed a combined technique (DORK+PLACE+averaging) to mitigate dynamic geometric distortion in EPI-based fMRI while preserving the temporal resolution. The performance of the combined DORK, PLACE and averaging technique was characterized through several imaging experiments involving test phantoms and six healthy adult volunteers. Phantom data illustrate reduced temporal standard deviation of fMRI signal intensities after use of combined dynamic PLACE, DORK and averaging compared to the standard processing and static geometric distortion correction. The combined technique also substantially improved the temporal standard deviation and activation maps obtained from human fMRI data in comparison to the results obtained by standard processing and static geometric distortion correction, highlighting the utility of the approach. PMID- 27258195 TI - Controlled reperfusion reduces hemorheological alterations in a porcine infrarenal aortic-clamping ischemia-reperfusion model. AB - INTRODUCTION: Restoration of blood flow after prolonged acute ischemia causes further injury to tissues. The role of increased oxidative stress is emphasized in the pathogenesis, and impairment of hemorheological factors may also hinder proper microcirculation. Controlled reperfusion at lowered pressure with diluted blood may help to decrease reperfusion injury. METHODS: Four-hour infrarenal aortic clamping was performed in 16 Yorkshire pigs. In 8 animals blood flow was restored subsequently (full reperfusion, FR), in the other 8 animals clamping was followed by an initial 30 minutes of controlled reperfusion (CR) at 60 mmHg pressure with a 1 : 1 ratio mixture of blood and reperfusion solution. Blood samples were taken before the intervention, at the end of ischemia, 15 minutes, 60 minutes, 1 day and 1 week after the start of reperfusion. Hemorheological parameters were measured. RESULTS: Hematocrit, plasma and whole blood viscosity decreased significantly during CR, these attenuated at 1 day. At 1 week whole blood and plasma viscosities were elevated in the FR group. Erythrocyte deformability did not change significantly at any measurements. Erythrocyte aggregation decreased during CR but not in FR, and was found elevated in both groups at 1 week. CONCLUSION: Our results suggest slightly improved hemorheological properties in case of controlled reperfusion compared to full reperfusion, which may help to reduce tissue damage. PMID- 27258196 TI - Parametric imaging with contrast-enhanced ultrasound for differentiating hepatocellular carcinoma from metastatic liver cancer. AB - AIM: To evaluate the diagnostic performance of parametric imaging with contrast enhanced ultrasound(CEUS) for differentiating hepatocellular carcinoma(HCC) from metastatic liver cancer(MLC). METHODS: 30 HCCs (mean diameter, 3.6+/-1.3 cm; range, 2.1-5.0 cm) and 30 MLCs (mean diameter, 2.8+/-1.5 cm; range, 1.2-5.0 cm) pathologically diagnosed or confirmed by clinical criteria that underwent CEUS were randomly included. CEUS was carried out using a multifrequency transducer (2 4 MHz) and a bolus injection of 2.4 mL SonoVue. The CEUS clips of the targeted lesion were recorded continuously for 6 minutes. By analyzing CEUS clips, parametric image could be obtained using the SonoLiver(r) software automatically. Quantitative parameters were compared between HCC and MLC groups. Receiver operating characteristic (ROC) curve analysis was further performed on parameters with significant difference between two groups. RESULTS: On parametric imaging, the maximum intensity, rise time, time to peak, mean transit time and washout time for HCC and MLC were 185.6+/-148.0 vs. 95.2+/-58.6 (P = 0.003), 25.7+/-6.3 s vs. 23.8+/-8.8 s (P = 0.341), 30.7+/-7.9 s vs. 27.8+/-10.5 s (P = 0.246), 90.2+/ 45.7 s vs. 89.3+/-40.3 s (P = 0.805), 63.4+/-29.5 s vs. 37.2+/-33.8 s (P = 0.005), respectively. ROC analysis was further performed for washout time and it showed a cut-off point of 43.765 s for the differentiation between HCC and MLC, with the AUC value of 0.780 (95% CI: 0.646-0.914). The corresponding diagnostic specificity, sensitivity and accuracy were 72.0%, 84.6% and 78.4% respectively. CONCLUSIONS: Parametric imaging of CEUS can display perfusion effects of HCC and MLC objectively and visually and washout time may serve as a useful parameter on the differential diagnosis between HCC and MLC. PMID- 27258197 TI - Regular walking improves plasma protein concentrations that promote blood hyperviscosity in women 65-74 yr with type 2 diabetes. AB - BACKGROUND: The purpose of the present study was to investigate the effects of regular treadmill walking on plasma factors that increase low-shear blood viscosity and red blood cell aggregation in older women with type 2 diabetes. METHODS: Eighteen women with type 2 diabetes (age: 69+/-3 yr; body mass index: 30.5+/-5.0 kg?m-2) performed 12-wk of 120 min?wk-1 of supervised treadmill walking at an intensity equivalent to the gas-exchange threshold. Peak exercise values, anthropometry and blood indices of diabetic status, markers of inflammation, and plasma fibrinogen were analysed during a 6-wk pre-training 'control' period, and then after 6 and 12-wk of regular walking. RESULTS: Regular walking significantly increased peak oxygen uptake (p = 0.01). Body mass, waist to hip ratio, and glycaemic control did not change. Systolic and diastolic blood pressures decreased by 8.5% (p < 0.01) and 7.2% (p < 0.01) respectively, cholesterol to high-density lipoprotein (HDL) ratio decreased by 9.6% (p = 0.01), and HDL concentration significantly increased (p = 0.01). While 12 wk of regular walking did not significantly alter plasma concentrations of interleukin-6 (IL 6), tumour necrosis factor-alpha, or C-reactive protein, plasma fibrinogen concentration decreased by 6.9% (p < 0.01) and plasma interleukin-10 (IL-10) concentration increased from 1.15+/-0.32 to 1.62+/-0.22 mmol?L-1 (p < 0.04). CONCLUSIONS: Improved plasma inflammatory profile and decreased plasma fibrinogen concentration is induced by regular walking, independent of glycaemic control. These factors may mediate the improved haemorheology associated with exercise training in metabolic disorders. PMID- 27258198 TI - Skin microvascular reactivity in patients with hypothyroidism. AB - Hypothyroidism is associated with impaired vascular function; however, little is known about its impact on microcirculation. We aimed to determine skin microvascular reactivity in hypothyroidism focusing on endothelial function and the sympathetic response. We measured skin laser Doppler (LD) flux (LDF) on the volar forearm and the finger pulp using LD flowmetry in hypothyroid patients (N = 13) and healthy controls (N = 15). Skin microvascular reactivity was assessed by a three-minute occlusion of the brachial artery, inducing postocclusive reactive hyperaemia (PRH), and by a four-minute local cooling of the hand. An electrocardiogram (ECG), digital artery blood pressure and skin temperature at the measuring sites were recorded. Baseline LDF, the digital artery blood pressure and the heart rate were comparable between patients and controls. On the other hand, patients exhibited significantly longer PRH duration, significantly higher blood pressure during cooling (unpaired t-test, p <0.05) and lower, albeit not significant, LDF in the ipsilateral finger pulp during cooling compared to controls. Unexpectedly, the results of the present study point to an increased vasodilator capacity of skin microcirculation and an apparent increase in sympathetic reactivity after local cooling in hypothyroid patients. Hypothyroidism induces subtle changes of some haemodynamic parameters in skin microcirculation implying altered endothelial function and altered sympathetic reactivity. PMID- 27258199 TI - Red blood cell deformability is reduced in homozygous sickle cell disease patients with leg ulcers. AB - Previous reports differ as to whether a decreased elongation index (EI), a proxy for red blood cell (RBC) deformability, is associated with leg ulcers (LU) in people with homozygous sickle cell disease (SCD). We sought to determine whether erythrocyte deformability (ED) and haematological indices were associated with the presence of LU in patients with SCD. The study design was cross-sectional. Twenty-seven patients with LU and 23 with no history of ulceration were recruited into the study. A laser assisted rotational red cell analyzer was used in the determination of the EI. Haematological indices were determined using a CELL-DYN Ruby haematology analyzer. Data were normally distributed and presented as means+/-SD. Two-sample t-test was used to test for associations between haemorheological variables in SCD patients with and without LU. Statistical significance was taken as p < 0.05. The EI was significantly lower in the group with ulcers (0.30+/-0.07 vs. 0.35+/-0.07, p = 0.02). Haematological indices were comparable in patients with and without LU. Erythrocyte deformability, but not haematological indices, was associated with LU in patients with SCD. PMID- 27258200 TI - Effects of haemoglobin levels on the sublingual microcirculation in pregnant women. AB - Anemia in pregnant women is associated with increased maternal and perinatal mortality and represents an important economic burden in many developing countries. Our goal was to evaluate the impact of anemia on the capillary network during pregnancy. Therefore, we compared microcirculatory parameters of anemic pregnant study participants to that of non-anemic pregnant women employing sublingual microcirculation video imaging technology and novel automated video analysis software.Non-anemic (n = 7) and anemic (n = 44) pregnant women were enrolled in the study at second and third trimesters. Video imaging was applied to the sublingual mucosal surface in five visual fields. The resultant videos were analyzed automatically, avoiding observer bias. Total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPV) were calculated by the software. Both, mean TVD and PVD were significantly increased in the anemic pregnant group, while the PPV was not significantly different. Significant negative correlations were observed between haemoglobin (Hb) levels and both, TVD and PVD. Haemoglobin level seems to play an important determinant role in restructuring the capillary network. An effect that could compensate the impaired tissue oxygen delivery associated with anemia during pregnancy. PMID- 27258201 TI - Characterization of cervical lymph nodes using DCE-MRI: Differentiation between metastases from SCC of head and neck and benign lymph nodes. AB - PURPOSES: To compare the characteristics of DCE-MRI between metastatic and benign lymph nodes (LNs). To explore the effect of sizes of LNs on the value of Ktrans, Ve and iAUC. MATERIALS AND METHODS: Metastatic and benign LNs were retrospectively analyzed. Chi-square test and two sample t-test were applied to TICs and parameters. One factor covariance analysis was used to explore the effect of diameters on the value of Ktrans, Ve and iAUC. RESULTS: The value of Ktrans, Ve and iAUC of metastatic LNs were statistically higher (all p < 0.001) than those of benign LNs. The short-axis diameters had no influence on parameters. CONCLUSIONS: DCE-MRI is useful to differentiate the metastatic LNs from benign LNs. Sizes of LNs has no effect on parameters. PMID- 27258202 TI - Identification of erythrocyte biomarkers in amyotrophic lateral sclerosis. AB - INTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. It has been hypothesised that red blood cells (RBCs) may be involved in the disease process by the release of damaging molecules. OBJECTIVE: The aim of this ex vivo study is to compare RBCs biochemical and hemorheological parameters between ALS patients and healthy donors to identify novel biomarkers of the ALS disease. METHODS: We included 82 ALS patients and 40 gender age-matched healthy donors. We performed quantification of erythrocyte aggregation and deformability, nitric oxide (NO) efflux from RBCs, acetylcholinesterase (AChE) enzyme activity and intraerythrocytic concentration of nitrite, nitrate and S-nitrosogluthatione (GSNO). RESULTS: Erythrocyte deformability and AChE activity were increased in patients with ALS in comparison to healthy donors. NO efflux from RBCs and concentration of intraerythrocytic nitrite were lower in ALS patients. In patients, we found that for higher NO range of values the respiratory function is worse and that for higher AChE range of values the RBCs nitrite content increase. CONCLUSION: The results of the present study indicate that NO efflux from RBCs and RBCs AChE should be further explored as potential biomarkers for ALS. PMID- 27258203 TI - Serum RDW and MPV in Ankylosing Spondylitis: Can they show the disease activity? AB - OBJECTIVE: To determine RDW and MPV levels in Ankylosing Spondylitis (AS) and to investigate their relations with disease activity. MATERIALS AND METHODS: 133 patients with AS (male: 80, female: 53) and age-sex matched 133 controls (male: 79, female: 54) were enrolled. Demographic data, disease activity scores, Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels were recorded. RESULTS: The mean ages of patients and controls were 41.9+/-11.2 and 39.7+/-14.2 years respectively (p = 0.16). RDW (14.5+/-1.6% and 13.2+/-0.8%, p < 0.0001 respectively) and MPV (10.1+/-0.8fl and 9.9+/-0.7fl, p = 0.03, respectively) were significantly higher in patients with AS than in controls. There was a significant difference in RDW between patients with active AS (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >4) and those with inactive AS (BASDI <4) patients (14.84+/-1.79fl, 14.24+/-1.37fl, p = 0.035 respectively). RDW was positively correlated with BASDAI (r = 0.33, P < 0.0001), ESR (r = 0.45, P < 0.0001) and CRP (r = 0.42, P < 0.0001) and PLT levels (r = 0.24, P = 0.004). While MPV was not correlated with BASDAI, it was negatively correlated with ESR (r = -0.19, P = 0.03), CPR (r = -0.26, P = 0.004) and PLT levels (r = -0.39, P = <0.0001). CONCLUSIONS: RDW and MPV were significantly higher in the patients with AS than in the controls. While RDW was correlated with BASDAI and APRs, MPV was only correlated with APRs. PMID- 27258204 TI - The effects of oral acetylsalicylic acid on blood fluidity and infusion speed in the cancer patients with PICC. AB - OBJECTIVE: This study aimed to examine the influence of oral acetylsalicylic acid on blood fluidity and infusion speed in the cancer patients with Peripherally Inserted Central Catheter (PICC). BACKGROUND: PICC is placed for prolonged chemotherapy of cancer patients. The fibrin sheaths, which consist of cellular substance and non-cellular substance, generate at the place of insertion and grow down all over the catheter. Finally they cover the vent of the catheter and lead to catheter dysfunctions such as the decrease of infusion speed. In addition, the high viscosity status of cancer patients could lead to acute embolization, which adds to the high risk of death. DESIGN: Randomized controlled trial. METHODS: This research was carried out between April 2013 and January 2014 in the second hospital of Xiangya, Central South University in Changsha, China. Initially 96 cancer participants with PICC were chosen and randomly allocated to experimental and control group. The participants of the experimental group were conducted route PICC maintain technique and took acetylsalicylic acid 100 mg per day after dinner, while the control group received route PICC maintain technique only. The infusion speed and hemorheology indexes of the two groups were tested before our study and at the end of the 2nd and 4th months with several instruments. RESULTS: Repeated measures analysis of variance indicated that taking acetylsalicylic acid orally had significant main effect on high shear blood viscosity and red blood cell deformability index (P < 0.05), and it also had significant main effect as well as time effect on plasma viscosity (P < 0.05); and time had significant main effect as well as interaction effect with oral acetylsalicylic acid on low shear blood viscosity and red blood cell aggregation index (P < 0.05). Repeated measures ANOVA also showed that taking acetylsalicylic acid orally had significant main effect, time effect and interaction effect on infusion speed (P < 0.01). CONCLUSION: Oral acetylsalicylic acid could improve hemorheology condition and the infusion speed related to fibrin sheath in the cancer patients. PMID- 27258205 TI - Altered microrheological parameters in Raynaud's phenomenon. AB - Raynaud's phenomenon is an episodic, painful attack of the acral parts caused by local diminished blood supply. The aim of our study was to examine hemorheological parameters, cold agglutinins, cryoglobulins and their relationship in patients suffering from Raynaud's phenomenon.Blood was taken from 74 patients (mean age: 48 years, female/male: 56/18). Cold agglutinins and cryoglobulins were determined. Hemorheological parameters were also measured such as hematocrit, plasma and whole blood viscosity, red blood cell aggregation and deformability. Results were compared to a group of 58 healthy controls (mean age: 31.5 years, female/male: 24/34).Cold agglutinins were positive in 70%, cryoglobulins in 43% of patients. When compared to healthy controls, increased red blood cell aggregation (64.54 +/- 8.93 vs. 61.11 +/- 7.05) and decreased red blood cell deformability (0.669 +/- 0.002 vs. 0.681 +/- 0.001) was observed in Raynaud's patients (p < 0.05), but there were no differences in hematocrit (43.27% +/- 3.85 vs. 44.10% +/- 3.70), plasma (1.27 mPas +/- 0.08 vs. 1.24 mPas +/- 0.09) and whole blood viscosity (4.12 mPas +/- 0.52 vs. 4.26 mPas +/- 0.46). No differences were found between the hemorheological profile of cold agglutinin/cryoglobulin positive and negative patients. Also primary and secondary Raynaud's patients had similar rheological profile.Erythrocyte aggregation and deformability seems to be unfavorable in Raynaud's patients that can play a role in the disturbance of the microcirculation. PMID- 27258206 TI - Exploring the Effect of Ligand Structural Isomerism in Langmuir-Blodgett Films of Chiral Luminescent Eu(III) Self-Assemblies. AB - Here we have investigated the influence of the antenna group position on both the formation of chiral amphiphilic Eu(III) -based self-assemblies in CH3 CN solution and, on the ability to form monolayers on the surface of quartz substrates using the Langmuir-Blodgett technique, by changing from the 1-naphthyl (2(R), 2(S)) to the 2-naphthyl (1(R), 1(S)) position. The evaluation of binding constants of the self- assemblies in CH3 CN solution was achieved using conventional techniques such as UV/Visible and luminescence spectroscopies along with more specific circular dichroism (CD) spectroscopy. The binding constants obtained for EuL, EuL2 and EuL3 species in the case of 2-naphthyl derivatives were comparable to those obtained for 1-naphthyl derivatives. The analysis of the changes in the CD spectra of 1(R) and 1(S) upon addition of Eu(III) not only allowed us to evaluate the values of the binding constants but the resulting recalculated spectra may also be used as fingerprints for assignment of the chiral self-assembly species formed in solution. The obtained monolayers were predominantly formed from EuL3 (~85 %) with the minor species present in ~15 % EuL2 . PMID- 27258207 TI - No detection of macrolide-resistant Mycoplasma pneumoniae from Swedish patients, 1996-2013. AB - BACKGROUND: Mycoplasma pneumoniae is a common cause of respiratory infections which can cause life-threatening pneumonia and serious extrapulmonary manifestations. Since the year 2000, the emergence of macrolide-resistant M. pneumoniae strains has increased with varying incidences across countries. In China more than 90% of the strains are resistant. M. pneumoniae diagnostics is mostly done with molecular methods, and in Sweden antibiotic resistance surveillance is not routinely performed. The prevalence of macrolide-resistant M. pneumoniae has not previously been studied in Sweden. MATERIAL AND METHODS: A total of 563 M. pneumoniae-positive respiratory samples, collected from four counties in Sweden between 1996 and 2013, were screened for mutations associated with macrolide resistance using a duplex FRET real-time PCR method. The real-time PCR targets the 23S rRNA gene, and differentiation between wild-type and resistant strains was achieved with a melting curve analysis. RESULTS: Of the 563 samples included, 548 were analyzed for mutations associated with macrolide resistance. No mutations were found. The detection rate of macrolide-resistant M. pneumoniae in this study was 0% [0.00-0.84%]. CONCLUSION: No macrolide-resistant M. pneumoniae has been detected in Sweden. However, the emergence and spread of macrolide-resistant M. pneumoniae strains in many countries commands continuous epidemiological surveillance. PMID- 27258209 TI - Traffic accidents and heavy episodic drinking among university students. PMID- 27258208 TI - Hantavirus in new geographic regions, Sweden. AB - In Sweden, human cases of Puumala hantavirus (PUUV) infections are reported from the northern endemic regions. We found hantavirus-specific antibodies in yellow necked mice (Apodemus flavicollis) trapped in human dwellings in the surroundings of the cities of Uppsala and Stockholm, which are situated far south from the traditional endemic areas of PUUV. Because the yellow-necked mouse is the most common rodent in human dwellings, hantaviruses in this rodent species may be important for the public health. PMID- 27258210 TI - Virtual-reality-based attention assessment of ADHD: ClinicaVR: Classroom-CPT versus a traditional continuous performance test. AB - Virtual-reality-based assessment may be a good alternative to classical or computerized neuropsychological assessment due to increased ecological validity. ClinicaVR: Classroom-CPT (VC) is a neuropsychological test embedded in virtual reality that is designed to assess attention deficits in children with attention deficit hyperactivity disorder (ADHD) or other conditions associated with impaired attention. The present study aimed to (1) investigate the diagnostic validity of VC in comparison to a traditional continuous performance test (CPT), (2) explore the task difficulty of VC, (3) address the effect of distractors on the performance of ADHD participants and typically-developing (TD) controls, and (4) compare the two measures on cognitive absorption. A total of 33 children diagnosed with ADHD and 42 TD children, aged between 7 and 13 years, participated in the study and were tested with a traditional CPT or with VC, along with several cognitive measures and an adapted version of the Cognitive Absorption Scale. A mixed multivariate analysis of covariance (MANCOVA) revealed that the children with ADHD performed worse on correct responses had more commissions and omissions errors than the TD children, as well as slower target reaction times . The results showed significant differences between performance in the virtual environment and the traditional computerized one, with longer reaction times in virtual reality. The data analysis highlighted the negative influence of auditory distractors on attention performance in the case of the children with ADHD, but not for the TD children. Finally, the two measures did not differ on the cognitive absorption perceived by the children. PMID- 27258211 TI - Notice of Retraction: Sato Y, et al. Effect of Folate and Mecobalamin on Hip Fractures in Patients With Stroke: A Randomized Controlled Trial. JAMA. 2005;293(9):1082-1088. PMID- 27258212 TI - Solar photo-ozonation: A novel treatment method for the degradation of water pollutants. AB - The decomposition of aqueous ozone by UV-vis radiation has been investigated with focus on the impact of ozone photolysis on the degradation of water pollutants during solar ozonation processes. The apparent first-order rate constants of the decomposition of ozone (kobs) have been determined at various pHs in the 4-9 range using radiation of different wavelengths in the UV-vis range. It was found that UVA-visible radiation (lambda>320nm) highly enhanced ozone decomposition, especially at pH 4, for which kobs was three-folded with respect to the process in the absence of radiation. Hydrogen peroxide was identified as a main intermediate of ozone photo-decomposition at pH 4. Experiments of degradation of oxalic acid by ozone showed that solar irradiation brings about an increase in the hydroxyl radical to ozone exposures ratio (Rct). Finally, photo-ozonation (lambda>300nm) was shown advantageous over single ozonation in the mineralization of a selection of emerging contaminants (metoprolol, ibuprofen, N,N-diethyl-meta toluamide and clofibric acid) in both ultrapure water and a synthetic secondary effluent. Thus, TOC removal in 2-h treatments increased from 10 to 25% in the absence of radiation to about 50% in the presence of radiation. PMID- 27258213 TI - A mesoscopic reaction rate model for shock initiation of multi-component PBX explosives. AB - The primary goal of this research is to develop a three-term mesoscopic reaction rate model that consists of a hot-spot ignition, a low-pressure slow burning and a high-pressure fast reaction terms for shock initiation of multi-component Plastic Bonded Explosives (PBX). Thereinto, based on the DZK hot-spot model for a single-component PBX explosive, the hot-spot ignition term as well as its reaction rate is obtained through a "mixing rule" of the explosive components; new expressions for both the low-pressure slow burning term and the high-pressure fast reaction term are also obtained by establishing the relationships between the reaction rate of the multi-component PBX explosive and that of its explosive components, based on the low-pressure slow burning term and the high-pressure fast reaction term of a mesoscopic reaction rate model. Furthermore, for verification, the new reaction rate model is incorporated into the DYNA2D code to simulate numerically the shock initiation process of the PBXC03 and the PBXC10 multi-component PBX explosives, and the numerical results of the pressure histories at different Lagrange locations in explosive are found to be in good agreements with previous experimental data. PMID- 27258214 TI - Systematic screening for the detection of atrial fibrillation. AB - BACKGROUND: Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is a leading cause of morbidity and mortality. Screening for AF in asymptomatic patients has been proposed as a way of reducing the burden of the disease by detecting people who would benefit from prophylactic anticoagulation therapy before the onset of symptoms. However, for screening to be an effective intervention, it must improve the detection of AF and provide benefit for those detected earlier as a result of screening. OBJECTIVES: This review aims to answer the following questions.Does systematic screening increase the detection of AF compared with routine practice? Which combination of screening population, strategy and test is most effective for detecting AF compared with routine practice? What safety issues and adverse events may be associated with individual screening programmes? How acceptable is the intervention to the target population? What costs are associated with systematic screening for AF? SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and EMBASE (Ovid) up to 11 November 2015. We searched other relevant research databases, trials registries and websites up to December 2015. We also searched reference lists of identified studies for potentially relevant studies, and we contacted corresponding authors for information about additional published or unpublished studies that may be relevant. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials comparing screening for AF with routine practice in people 40 years of age and older were eligible. Two review authors (PM and CT) independently selected trials for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors (PM and CT) independently assessed risk of bias and extracted data. We used odds ratios (ORs) and 95% confidence intervals (CIs) to present results for the primary outcome, which is a dichotomous variable. As we identified only one study for inclusion, we performed no meta-analysis. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) method to assess the quality of the evidence and GRADEPro to create a 'Summary of findings' table. MAIN RESULTS: One cluster-randomised controlled trial met the inclusion criteria for this review. This study compared systematic screening (by invitation to have an electrocardiogram (ECG)) and opportunistic screening (pulse palpation during a general practitioner (GP) consultation for any reason, followed by an ECG if pulse was irregular) versus routine practice (normal case finding on the basis of clinical presentation) in people 65 years of age or older.Results show that both systematic screening and opportunistic screening of people over 65 years of age are more effective than routine practice (OR 1.57, 95% CI 1.08 to 2.26; and OR 1.58, 95% CI 1.10 to 2.29, respectively; both moderate-quality evidence). We found no difference in the effectiveness of systematic screening and opportunistic screening (OR 0.99, 95% CI 0.72 to 1.37; low-quality evidence). A subgroup analysis found that systematic screening and opportunistic screening were more effective in men (OR 2.68, 95% CI 1.51 to 4.76; and OR 2.33, 95% CI 1.29 to 4.19, respectively) than in women (OR 0.98, 95% CI 0.59 to 1.62; and OR 1.2, 95% CI 0.74 to 1.93, respectively). No adverse events associated with screening were reported.The incremental cost per additional case detected by opportunistic screening was GBP 337, compared with GBP 1514 for systematic screening. All cost estimates were based on data from the single included trial, which was conducted in the UK between 2001 and 2003. AUTHORS' CONCLUSIONS: Evidence suggests that systematic screening and opportunistic screening for AF increase the rate of detection of new cases compared with routine practice. Although these approaches have comparable effects on the overall AF diagnosis rate, the cost of systematic screening is significantly greater than the cost of opportunistic screening from the perspective of the health service provider. Few studies have investigated effects of screening in other health systems and in younger age groups; therefore, caution needs to be exercised in relation to transferability of these results beyond the setting and population in which the included study was conducted.Additional research is needed to examine the effectiveness of alternative screening strategies and to investigate the effects of the intervention on risk of stroke for screened versus non-screened populations. PMID- 27258215 TI - Noninvasively measuring oxygen saturation of human finger-joint vessels by multi transducer functional photoacoustic tomography. AB - Imaging small blood vessels and measuring their functional information in finger joint are still challenges for clinical imaging modalities. In this study, we developed a multi-transducer functional photoacoustic tomography (PAT) system and successfully imaged human finger-joint vessels from ~1 mm to <0.2 mm in diameter. In addition, the oxygen saturation (SO2) values of these vessels were also measured. Our results demonstrate that PAT can provide both anatomical and functional information of individual finger-joint vessels with different sizes, which might help the study of finger-joint diseases, such as rheumatoid arthritis. PMID- 27258216 TI - Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers. AB - This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0+/-0.6%. In vitro stability was retained upto 4 days at 37 degrees C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF. PMID- 27258217 TI - Seasonal variations of decay rate measurement data and their interpretation. AB - Measurement data of long-lived radionuclides, for example, (85)Kr, (90)Sr, (108m)Ag, (133)Ba, (152)Eu, (154)Eu and (226)Ra, and particularly the relative residuals of fitted raw data from current measurements of ionization chambers for half-life determination show small periodic seasonal variations with amplitudes of about 0.15%. The interpretation of these fluctuations is a matter of controversy whether the observed effect is produced by some interaction with the radionuclides themselves or is an artifact of the measuring chain. At the origin of such a discussion there is the exponential decay law of radioactive substances used for data fitting, one of the fundamentals of nuclear physics. Some groups of physicists use statistical methods and analyze correlations with various parameters of the measurement data and, for example, the Earth-Sun distance, as a basis of interpretation. In this article, data measured at the Physikalisch Technische Bundesanstalt and published earlier are the subject of a correlation analysis using the corresponding time series of data with varying measurement conditions. An overview of these measurement conditions producing instrument instabilities is given and causality relations are discussed. The resulting correlation coefficients for various series of the same radionuclide using similar measurement conditions are in the order of 0.7, which indicates a high correlation, and for series of the same radionuclide using different measurement conditions and changes of the measuring chain of the order of -0.2 or even lower, which indicates an anti-correlation. These results provide strong arguments that the observed seasonal variations are caused by the measuring chain and, in particular, by the type of measuring electronics used. PMID- 27258218 TI - Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications. AB - Two-dimensionally extended, polycyclic heteroaromatic molecules (heterocyclic nanographenes) are a highly versatile class of organic materials, applicable as functional chromophores and organic semiconductors. In this Review, we discuss the rich chemistry of large heteroaromatics, focusing on their synthesis, electronic properties, and applications in materials science. This Review summarizes the historical development and current state of the art in this rapidly expanding field of research, which has become one of the key exploration areas of modern heterocyclic chemistry. PMID- 27258219 TI - A Case Series of Acute Myocardial Infarction in Left Ventricular Assist Device Supported Patients. AB - Acute myocardial infarction (AMI) is an underrecognized phenomenon in patients with continuous-flow left ventricular assist devices (CF-LVAD). Previously, there has been an optimistic expectation of a benign clinical course; however, AMI in LVAD-supported patients can result in profound consequences and management remains controversial. We describe a case series of AMI in four CF-LVAD patients, each with a different presentation, clinical course, treatment, and outcome. The clinical variability and mixed outcomes of these patients highlights the unique challenges in diagnosis and management of AMI in this population, particularly the uncertain role of percutaneous intervention (PCI), and underscores the potentially poor prognosis of this entity. Several key points emerge from this review. First, LVAD-supported patients frequently have underlying abnormalities on the electrocardiogram (ECG) that obscure the diagnosis of AMI. Second, clinicians should have a high degree of suspicion for AMI in the presence of suggestive clinical features, elevated cardiac biomarkers, or new-onset ventricular arrhythmias. Third, the decision to proceed with PCI requires careful evaluation of the risk of hemorrhage, and strong consideration should be given to the use of bleeding avoidance strategies during and after PCI. PMID- 27258220 TI - Electron Microscopy as a Tool for Assessment of Anticoagulation Strategies During Extracorporeal Life Support: The Proof Is on the Membrane. AB - Extracorporeal life support (ECLS) is fast becoming more common place for use in adult patients failing mechanical ventilation. Management of coagulation and thrombosis has long been a major complication in the use of ECLS therapies. Scanning electron microscopy (SEM) of membrane oxygenators (MOs) after use in ECLS circuits can offer novel insight into any thrombotic material deposition on the MO. In this pilot study, we analyzed five explanted MOs immediately after use in a sheep model of different acute respiratory distress syndrome (ARDS). We describe our methods of MO dissection, sample preparation, image capture, and results. Of the five MOs analyzed, those that received continuous heparin infusion showed very little thrombosis formation or other clot material, whereas those that were used with only initial heparin bolus showed readily apparent thrombotic material. PMID- 27258221 TI - Optimization of Centrifugal Pump Characteristic Dimensions for Mechanical Circulatory Support Devices. AB - The application of artificial mechanical pumps as heart assist devices impose power and size limitations on the pumping mechanism, and therefore requires careful optimization of pump characteristics. Typically new pumps are designed by relying on the performance of other previously designed pumps of known performance using concepts of fluid dynamic similarity. Such data are readily available for industrial pumps, which operate in Reynolds numbers region of 10. Heart assist pumps operate in Reynolds numbers of 10. There are few data available for the design of centrifugal pumps in this characteristic range. This article develops specific speed versus specific diameter graphs suitable for the design and optimization of these smaller centrifugal pumps concentrating in dimensions suitable for ventricular assist devices (VADs) and mechanical circulatory support (MCS) devices. A combination of experimental and numerical techniques was used to measure and analyze the performance of 100 optimized pumps designed for this application. The data are presented in the traditional Cordier diagram of nondimensional specific speed versus specific diameter. Using these data, nine efficient designs were selected to be manufactured and tested in different operating conditions of flow, pressure, and rotational speed. The nondimensional results presented in this article enable preliminary design of centrifugal pumps for VADs and MCS devices. PMID- 27258223 TI - Acute Biventricular Interaction in Pediatric Patients Implanted with Continuous Flow and Pulsatile Flow LVAD: A Simulation Study. AB - Left ventricular assist devices (LVADs) are used to bridge pediatric patients till transplantation. However, the LVADs effects on right ventricular (RV) function are controversial. This work aims at studying the ventricular interdependency in the presence of continuous (c-) and pulsatile (p-) flow LVAD in pediatric patients using a lumped parameter model including the representation of the septum. Five pediatric patients' data were used to simulate patients' baseline. The effects on LV and RV functions, energetics, preloads and afterloads of different c-LVAD speeds, p-LVAD rate, p-LVAD systole duration, p-LVAD filling and ejection pressures were simulated. c-LVAD and p-LVAD unload the LV decreasing the LV external work and improving the LV ventriculo-arterial coupling and these effects are more evident increasing the c-LVAD speed and the p-LVAD rate. Continuous-LVAD and p-LVAD decrease the RV afterload, increase the RV ejection fraction and improve the RV ventriculo-arterial coupling. The changes in RV function are inversely proportional to the degree of the interventricular septum leftward shift that increased by increasing the LVAD contribution. The study of the interventricular interaction could lead to the development of a dedicated algorithm to optimize LVAD setting in pediatric population. PMID- 27258222 TI - Immunomodulatory Device Promotes a Shift of Circulating Monocytes to a Less Inflammatory Phenotype in Chronic Hemodialysis Patients. AB - Patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD) suffer accelerated morbidity and mortality rates caused by cardiovascular disease and infections. Chronic inflammation plays a critical role in these poor outcomes. The activated monocyte (MO) has become a prime therapeutic target to modulate this inflammatory process. A selective cytopheretic device (SCD) was evaluated to assess its effects on the circulating MO pool. A pilot trial was undertaken in 15 ESRD patients on HD with C-reactive protein (CRP) levels greater than 5 mg/dl. An excellent safety profile was observed with no decline in leukocyte (LE) or platelet counts. The effect of SCD therapy on MO phenotypes in these patients was determined on peripheral blood MO utilizing flow cytometry. SCD therapy promoted a shift in MO phenotype from predominantly CD14 expressing MO at baseline/pre-SCD therapy to CD14 expressing MO post-SCD therapy. A significant shift in MO population phenotype afforded by a single SCD therapy session was observed (p < 0.013). In a subset of patients (n = 7) presenting with type 2 diabetes mellitus (T2D), this persistent decline in MO CD14 expression was sustained as long as 2 weeks posttherapy. These results demonstrate that the SCD therapy has the potential to modulate the chronic proinflammatory state in ESRD patients. PMID- 27258225 TI - Permanent Continuous Flow Left Ventricular Assist Devices Use After Acute Stabilization for Cardiogenic Shock in Acute Myocardial Infarction. AB - Cardiogenic shock complicating acute myocardial infarctions (CS-AMIs) carries high mortality rates. Early use of durable continuous flow left ventricular assist devices (CF-LVAD) in these patients has traditionally been discouraged. Therefore we sought to assess the efficacy and complications of CF-LVAD use in CS AMI after stabilization with temporary mechanical support. From January 2006 to November 2014, nine patients underwent CF-LVAD implant after CS-AMI (Heartmate II, six; HVAD, three). All patients required temporary mechanical circulatory support (MCS) before CF-LVAD implant and were interagency registry for mechanically assisted circulatory support profile 1; average time from MI to CF LVAD implant was 20 days. Overall seven of nine patients (78%) survived to discharge. Survival at 1, 3, 12, and 48 months was 100%, 89%, 67%, and 67%, respectively. Two patients were successfully bridged to transplant and four patients remain alive on device support. The most common post-LVAD complication was stroke, occurring in 55% of patients. Embolic strokes were mild in severity and all patients survived with only mild deficits; hemorrhagic strokes conferred the highest mortality. This study suggests CF-LVADs are potential but high-risk treatment options for CS-AMI patients who stabilize with temporary support. Further studies will help more clearly delineate the benefits and risks of CF LVAD implant in this population. PMID- 27258224 TI - Effect of CYP2C9 and VKORC1 Gene Variants on Warfarin Response in Patients with Continuous-Flow Left Ventricular Assist Devices. AB - Bleeding and thrombotic complications continue to plague continuous-flow left ventricular assist device (CF-LVAD) therapy in patients with end-stage heart failure. Warfarin genotyping information can be incorporated into decision making for initial dosing as recommended by the Food and Drug Administration; however, clinical utility of this data in the CF-LVAD population has not been well studied. Genotypes testing for CYP2C9 and VCORC1 polymorphisms were determined in 90 CF-LVAD patients. Outcomes studied were the association of CYP2C9 (*1, *2, or *3) and VKORC1 (-1639 G>A) gene variants with time-to-target international normalized ratio (INR), total warfarin dose, maintenance warfarin dose. Continuous-flow left ventricular assist device patients carrying a rare variant in the VKORC1 gene had a significantly lower cumulative warfarin dose until target INR achieved (18.9 vs. 35.0 mg, p = 0.002), days spent until INR target achieved (4.9 vs. 7.0 days, p = 0.021), and discharge warfarin dose (3.2 vs. 5.6 mg, p = 0.001) compared with patients with wild-type genotype. Genotype-guided warfarin dosing may lead to safer anticoagulation and potentially improve outcomes in CF-LVAD patients. PMID- 27258226 TI - Donor Oversizing Results in Improved Survival in Patients with Left Ventricular Assist Device. AB - Donor to recipient undersizing can result in diminished graft survival. The United Network for Organ Sharing database was retrospectively queried from January 2008 to December 2013 to identify adult patients who underwent heart transplantation. This population was divided into those without and with a left ventricular assist device (LVAD) at the time of transplant. Both groups were further subdivided into three groups: donor:recipient body mass index (BMI) ratio <0.8 (undersized), >=0.8 and <=1.2 (matched), and >1.2 (oversized). Kaplan-Meier analysis was used to compare graft survival. Cox regression analysis was used to identify factors affecting graft survival time. There was no difference in mean graft survival between undersized, matched, and oversized groups in patients without an LVAD (p = 0.634). Mean graft survival was significantly worse for undersized patients with an LVAD when compared with matched and oversized patients (p = 0.032). Cox regression revealed age, creatinine, waitlist time, United Network for Organ Sharing status, BMI ratio, and total bilirubin as significant factors affecting graft survival time. A donor to recipient BMI ratio of >=1.2 results in significantly improved long-term graft survival for patients with an LVAD at the time of heart transplantation compared with patients with a BMI ratio of <1.2. An oversized organ should be considered for patients supported with an LVAD. PMID- 27258227 TI - Development of Risk Indices for Neonatal Respiratory Extracorporeal Membrane Oxygenation. AB - Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has saved thousands of newborns. Population comparisons for research and quality initiatives require risk-matching, but no indices exist for this population. We sought to create a pre-ECMO risk index using the registry data from the Extracorporeal Life Support Organization. We analyzed 5,455 neonatal (<30 days old) respiratory VA-ECMO patients for the period 2000-2010. Multivariate regression examining the impact of pre-ECMO variables on survival to hospital discharge was performed to create the Pittsburgh Index for Pre-ECMO Risk (PIPER), which was ultimately was based on seven pre-ECMO variables. Each PIPER quartile demonstrated increasing mortality by 15% (R = 0.98) and was associated with increased complications on ECMO. Further modeling to include on-ECMO complications (PIPER), including complications and length of time on ECMO, increased the predictive power of the model, with 21% increases in mortality per PIPER quartile (R = 0.97). Our developed indices provide the first steps towards risk-adjusting patients for meaningful comparisons amongst patient populations. There may be additional clinically relevant measures, both pre- and on-ECMO, which could provide better predictive capability. Future work will focus on finding these additional measures and expansion of our techniques to include other patient populations. PMID- 27258228 TI - Outcomes of Various Treatment Strategies for Patients with Continuous-Flow Ventricular Assist Device Thrombosis: A Retrospective Analysis. AB - Pump thrombosis is associated with high morbidity and mortality in patients with a continuous-flow left ventricular assist device. Although it has been defined clearly, the diagnosis and treatment of this complication still remain controversial. Between 2010 and 2014, 163 consecutive patients (mean age: 50.7 +/ 13 years, 84% males, median duration of support: 277 (2-1077) days) were implanted a continuous-flow left ventricular assist device. Prospectively collected data of all patients who had at least one pump thrombosis event have been analyzed, retrospectively. Twenty-one pump thrombosis events were observed in 15 patients (9.2%, 0.137 events/patient-year). Median duration of support at the time of first pump thrombosis event was 259 (8-585) days. Overall mortality was 40% (6/15), and overall procedural success was 71.4% (15/21) in our entire cohort. The cause of mortality was hemorrhagic stroke in those who had medical treatment (n = 5), and sepsis and right ventricular failure in the other who had pump exchange. Pump exchange was performed in five patients, of which four survived. Glycoprotein IIb/IIIa antagonists are not beneficial in medical treatment of pump thrombosis. Medical treatment methods including unfractionated heparin and thrombolytics may completely resolve the thrombus and save some patients from pump exchange. In patients where medical treatment does not result in complete thrombus resolution within a reasonable period, and a donor heart is not available, pump exchange is the ultimate solution. Further studies are needed for optimal dosing of thrombolytics to decrease the rate of side effects. PMID- 27258229 TI - Costs and Outcomes in the Care of Bi-ventricular Support as a Bridge to Cardiac Transplant. AB - Bi-ventricular (Bi-V) mechanical circulatory support is commonly used as a bridge to cardiac transplant. However, the optimal strategy is unknown. We examined the outcomes, as well as the costs in the use of Bi-V support as a bridge to cardiac transplant. From 2001 to 2014, three different Bi-V support strategies were utilized: 1) Para-corporeal ventricular assist device (PVAD-2001-2006), 2) Heartmate II left ventricular assist device in conjunction with a temporary CentriMag right ventricular assist device (HMII + CMAG-2006-2012), and the total artificial heart (TAH-2012-2014). Total costs were derived from the hospitalization at implant, and postimplant costs defined as equipment and re hospitalizations before transplantation. Sixty-five (34 PVADs, 20 HMII + CMAG, and 11 TAHs) devices were used as a bridge for transplant. There were no differences in implant variables including age, INTERMACS score, or implant length of stay. Although the wait list mortality was not different between groups (PVAD-32%, HMII + CMAG-45%, TAH-54%; p = 0.3), the percentage of patients transplanted were highest in the PVAD group: (PVAD-55.8%, HMII + CMAG-30.0%, TAH 18.2%; p = 0.01). Total costs were not significantly different between groups (PVAD-$306,166 +/- 247,839, HMII + CMAG-$278,958 +/- 135,324, TAH-$321,387 +/- 21,2477; p = 0.5). Despite variations in therapy, outcomes and costs for patients requiring Bi-V support as a bridge to cardiac transplant have remained constant. PMID- 27258230 TI - Sex-Related Differences in Inflammatory and Immune Activation Markers Before and After Combined Antiretroviral Therapy Initiation. AB - BACKGROUND: Women progress to death at the same rate as men despite lower plasma HIV RNA (viral load). We investigated sex-specific differences in immune activation and inflammation as a potential explanation. METHODS: Inflammatory and immune activation markers [interferon gamma, tumor necrosis factor (TNF) alpha, IL-6, IL-18, IFN-gamma-induced protein 10, C-reactive protein (CRP), lipopolysaccharide, and sCD14] were measured at weeks 0, 24, and 48 after combination antiretroviral therapy (cART) in a random subcohort (n = 215) who achieved virologic suppression in ACTG A5175 (Prospective Evaluation of Antiretrovirals in Resource-Limited Settings). Association between sex and changes in markers post-cART was examined using random effects models. Average marker differences and 95% confidence intervals were estimated using multivariable models. RESULTS: At baseline, women had lower median log10 viral load (4.93 vs 5.18 copies per milliliter, P = 0.01), CRP (2.32 vs 4.62 mg/L, P = 0.01), detectable lipopolysaccharide (39% vs 55%, P = 0.04), and sCD14 (1.9 vs 2.3 ug/mL, P = 0.06) vs men. By week 48, women had higher interferon gamma (22.4 vs 14.9 pg/mL, P = 0.05), TNF-alpha (11.5 vs 9.5 pg/mL, P = 0.02), and CD4 (373 vs 323 cells per cubic millimeter, P = 0.02). In multivariate analysis, women had greater increases in CD4 and TNF-alpha but less of a decrease in CRP and sCD14 compared with men. CONCLUSIONS: With cART-induced viral suppression, women have less reduction in key markers of inflammation and immune activation compared with men. Future studies should investigate the impact of these sex-specific differences on morbidity and mortality. PMID- 27258231 TI - Brief Report: CD14brightCD16- monocytes and sCD14 level negatively associate with CD4-memory T-cell frequency and predict HCV-decline on therapy. AB - During HIV+ hepatitis C virus (HCV)+ coinfection CD14CD16 monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-alpha treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenza-specific IFN gamma-response before and during IFN-alpha treatment. Effector-memory and central memory CD4 T-cell frequencies were lower in HCV+ HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14CD16 monocytes, and plasma sCD14. sCD14 and CD14CD16 monocytes negatively correlated with IFN-alpha dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza(CEF)-specific IFN-gamma response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF specific IFN-gamma response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14CD16-monocyte frequency to the failure of IFN-dependent HCV clearance. PMID- 27258232 TI - Brief Report: HIV-1 Infection Impairs CD16 and CD35 Mediated Opsonophagocytosis of Mycobacterium tuberculosis by Human Neutrophils. AB - Using a flow cytometric assay, we investigated neutrophil-Mycobacterium tuberculosis opsonophagocytosis and the impact of HIV-1-infected serum on this process. The mean (+/-SD) percentage of neutrophils internalizing bacilli after 30 minutes incubation was significantly reduced by pretreatment with anti-CD16 (18.2% +/- 8.1%, P < 0.001) or anti-CD35 antibody (23.2% +/- 10.6%, P < 0.05) versus anti-CD4 controls (29.9% +/- 8.1%). Blocking CD88 or CD11a did not affect internalization. Using heat-inactivated serum, maximal internalization was lower using HIV-1-infected serum versus HIV-1-uninfected. Using non-heat-inactivated serum, internalization decreased more rapidly with sequential dilutions of HIV-1 infected versus HIV-1-uninfected serum. CD16 and CD35 are important for neutrophil internalization of M. tuberculosis, whereas HIV-1 infection adversely affects opsonophagocytosis. PMID- 27258234 TI - Brief Report: European Mitochondrial Haplogroups Impact on Liver Fibrosis Progression Among HCV and HIV/HCV-Coinfected Patients From Northwest Spain. AB - The impact of mitochondrial DNA haplogroups on the outcome of liver fibrosis was evaluated in 362 hepatitis C virus infection (HCV)-monoinfected and HIV/HCV coinfected patients (147 and 215, respectively) in clinical follow-up at 2 reference hospitals in the Northwest of Spain. The mitochondrial DNA haplogroup H was the most prevalent (50.3%) in this population. The cluster Others and V were recognized as risk factors for the development of liver fibrosis while haplogroup H and HCV genotype 4 confer a lower risk. This information might be useful for prioritization of HCV treatment, especially for F0-F1 patients for whom there is no urgency for treatment. PMID- 27258233 TI - Critical Review: When the Party is Over: A Systematic Review of Behavioral Interventions for Substance-Using Men Who Have Sex with Men. AB - Because problematic patterns of alcohol and other substance use are prevalent drivers of the HIV/AIDS epidemic, comprehensive interventions are needed for substance-using men who have sex with men (SUMSM). We conducted a systematic review of 12 randomized controlled trials (RCTs) of behavioral interventions for reducing condomless anal intercourse (CAI) in SUMSM. Three RCTs observed that cognitive behavioral or motivational interviewing interventions achieved a 24% to 40% decrease in CAI. Interventions also tended to demonstrate greater efficacy for reducing CAI and substance use among those who had lower severity of substance use disorder symptoms. Although behavioral interventions for SUMSM are one potentially important component of biobehavioral HIV/AIDS prevention, further research is needed to examine whether integrative approaches that cultivate resilience and target co-occurring syndemic conditions demonstrate greater efficacy. Multilevel intervention approaches are also needed to optimize the effectiveness of pre-exposure prophylaxis and HIV treatment as prevention with SUMSM. PMID- 27258235 TI - Antimicrobial and Physicochemical Characterization of Biodegradable, Nitric Oxide Releasing Nanocellulose-Chitosan Packaging Membranes. AB - Biodegradable composite membranes with antimicrobial properties consisting of nanocellulose fibrils (CNFs), chitosan, and S-nitroso-N-acetyl-d-penicillamine (SNAP) were developed and tested for food packaging applications. As a nitric oxide donor, SNAP was encapsulated into completely dispersed chitosan in 100 mL of 0.1 N acetic acid and was thoroughly mixed with CNFs to produce a composite membrane. The fabricated membranes had a uniform dispersion of chitosan and SNAP within the CNFs, which was confirmed through scanning electron microscopy (SEM) micrographs and a chemiluminescence nitric oxide analyzer. The membranes prepared without SNAP showed lower water vapor permeability than that of the membranes with SNAP. The addition of SNAP resulted in a decrease in Young's modulus for both two- and three-layer membrane configurations. Antimicrobial property evaluation of SNAP-incorporated membranes showed an effective zone of inhibition against bacterial strains of Enterococcus faecalis, Staphylococcus aureus, and Listeria monocytogenes and demonstrated its potential applications for food packaging. PMID- 27258236 TI - Endometrial 'scratching': what the data show. AB - PURPOSE OF REVIEW: Since its first description in 2003, the endometrial scratching procedure has been the topic of over 1000 studies. This procedure, used to improve endometrial receptivity for assisted reproduction, is accessible any gynecologist can easily perform it - and has been adapted into clinical routine by some reproductive units. However, the available data are controversial, and no biological plausibility exists to support the use of this intervention. This study aims to critically review the existing data, focusing on the last 2 years, regarding the efficiency of endometrial scratching. RECENT FINDINGS: A total of five randomized controlled studies, one meta-analysis, and a systematic review related to endometrial scratching/injury were published in 2014 and 2015. Considerable heterogeneity exists among these studies regarding the selected population, type of treatment, and even timing and devices used to perform the endometrial injury. Importantly, none of these studies reported improved reproductive outcomes in terms of live birth rates following endometrial scratching. SUMMARY: Overall, data from properly designed and powered randomized controlled studies demonstrate no beneficial effect of this intervention that is based on unknown biological effects. Endometrial scratching produces pain, costs money, and the side-effects of systematic scratching in the production of Asherman syndrome remain to be seen. Think before scratching. PMID- 27258237 TI - Hysteroscopy safety. AB - PURPOSE OF REVIEW: Hysteroscopy is a very common tool providing the gynecologist the ability to diagnose and treat a variety of intrauterine disorders. This outpatient therapy has provided quick and effective relief for women worldwide. Although simple in concept, hysteroscopy is associated with minor and major complications. Awareness of these difficulties and methods of prevention and management is key to good surgical outcomes. This article reviews well tolerated practices for hysteroscopy complications. RECENT FINDINGS: Although complications with both diagnostic and operative hysteroscopy are rare, they can often be prevented with thorough preoperative evaluation and appropriate intraoperative decision making. Understanding the patient, disorder, and surgical process can assist the surgeon in providing the best outcome for the patient. SUMMARY: With appropriate training and education, gynecologists can safely incorporate hysteroscopy into their surgical practice. PMID- 27258238 TI - Organocatalyzed Intramolecular Carbonyl-Ene Reactions. AB - An organocatalyzed intramolecular carbonyl-ene reaction was developed to produce carbocyclic and heterocyclic 5- and 6-membered rings from a citronellal-derived trifluoroketone and a variety of aldehydes. A phosphoramide derivative was found to promote the cyclization of the trifluoroketone, whereas a less acidic phosphoric acid proved to be a superior catalyst for the aldehyde substrates. PMID- 27258239 TI - Dendrimer Prodrugs. AB - The main objective of this review is to describe the importance of dendrimer prodrugs in the design of new drugs, presenting numerous applications of these nanocomposites in the pharmaceutical field. Therefore, the use of dendrimer prodrugs as carrier for drug delivery, to improve pharmacokinetic properties of prototype, to promote drug sustained-release, to increase selectivity and, consequently, to decrease toxicity, are just some examples of topics that have been extensively reported in the literature, especially in the last decade. The examples discussed here give a panel of the growing interest dendrimer prodrugs have been evoking in the scientific community. PMID- 27258240 TI - Methyl Jasmonate: An Alternative for Improving the Quality and Health Properties of Fresh Fruits. AB - Methyl jasmonate (MeJA) is a plant growth regulator belonging to the jasmonate family. It plays an important role as a possible airborne signaling molecule mediating intra- and inter-plant communications and modulating plant defense responses, including antioxidant systems. Most assessments of this compound have dealt with post-harvest fruit applications, demonstrating induced plant resistance against the detrimental impacts of storage (chilling injuries and pathogen attacks), enhancing secondary metabolites and antioxidant activity. On the other hand, the interactions between MeJA and other compounds or technological tools for enhancing antioxidant capacity and quality of fruits were also reviewed. The pleiotropic effects of MeJA have raisen numerous as-yet unanswered questions about its mode of action. The aim of this review was endeavored to clarify the role of MeJA on improving pre- and post-harvest fresh fruit quality and health properties. Interestingly, the influence of MeJA on human health will be also discussed. PMID- 27258241 TI - Hydrazino-methoxy-1,3,5-triazine Derivatives' Excellent Corrosion Organic Inhibitors of Steel in Acidic Chloride Solution. AB - The corrosion inhibition performance of 2-hydrazino-4,6-dimethoxy-1,3,5-tirazine (DMeHT), 2,4-dihydrazino-6-methoxy-1,3,5-triaizine (DHMeT), and 2,4,6 tridydrazino-1,3,5-triaizne (TH3) on steel corrosion in acidic media was examined using electrochemical techniques. The results showed 2,4-Ddihydrazino-6-methoxy 1,3,5-triaizine (DHMeT) gave the best corrosion protection performance among the other hydrazino derivatives even at a low concentration of 25 ppm (95%). The number of hydrazino groups play an important role in the corrosion inhibition, where the two hydrazine groups increased the electrostatic interactions between the protonated tested compounds, the negatively charged steel surface resulted from the adsorption of the chloride anions, and the presence of the methoxy group made the compound more reliable for formation of film protection on the surface of steel through the lone pair of oxygen atoms. Electrochemical Impedance Spectroscopy (EIS) measurements suggested that the corrosion process of steel in presence of the hydrazino-s-triazine derivatives (TH3, DMeHT and DHMeT) were being controlled by the charge transfer reaction. Polarization curves indicated that the examined TH3, DMeHT and DHMeT behaved as mixed type inhibitors. PMID- 27258242 TI - Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4 Propoxybenzoates and Their Hydrochloride Salts. AB - Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of protonation of nitrogen atoms in the piperazine ring of hydrochloride salts was determined by means of (13)C-CP/MAS and (15)N-CP/MAS NMR and IR spectroscopy. Using these solid-state analytical techniques, it was found that both nitrogen atoms were protonated when excess hydrogen chloride was used for preparation of salts. On the other hand, when the equimolar amount of hydrogen chloride was used, piperazine nitrogen substituted by aryl was protonated. PMID- 27258243 TI - A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy. AB - This study aimed to examine the efficacy of epirubicin-loaded gelatin hydrogel (EPI-H) in the treatment of superficial urothelium carcinoma. Hydrogel was prepared by Schiff base-crosslinking of gelatin with glutaraldehyde. EPI-H exhibited high entrapment efficiency (59.87% +/- 0.51%). EPI-H also increased epirubicin accumulation in AY-27 cells when compared with the effect of aqueous solutions of epirubicin (EPI-AQ); respective epirubicin-positive cell counts were 69.0% +/- 7.6% and 38.3% +/- 5.8%. EPI-H also exhibited greater cytotoxicity against AY-27 cells than that of EPI-AQ; IC50 values were 13.1 +/- 1.1 and 7.5 +/ 0.3 MUg/mL, respectively. Cystometrograms showed that EPI-H reduced peak micturition, threshold pressures, and micturition duration, and that it increased bladder compliance more so than EPI-AQ. EPI-H enhanced epirubicin penetration into basal cells of urothelium in vivo, whereas EPI-AQ did so only to the umbrella cells. EPI-H inhibited tumor growth upon intravesical instillation to tumor-bearing bladder of F344 rats, inducing higher levels of caspase-3 expression than that observed with EPI-AQ treatment; the number of caspase-3 positive cells in treated urothelium carcinoma was 13.9% +/- 4.0% (EPI-AQ) and 34.1% +/- 1.0%, (EPI-H). EPI-H has value as an improved means to administer epirubicin in intravesical instillation treatments for bladder cancer. PMID- 27258244 TI - Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract. AB - A specific, simple, sensitive Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) method has been developed and validated for the simultaneous determination and pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. Chromatographic separation was carried out using a C18 column (ACQUITY UPLC((r)) HSS T3, 1.8 MUm, 2.1 * 100 mm) with gradient elution. The compounds were detected on a 6430 triple-quadrupole tandem MS with an electrospray ionization (ESI) interface using multiple reaction monitoring (MRM) in positive ionization mode. The samples were prepared by a liquid-liquid extraction (LLE) method with ethyl acetate after being spiked with an internal standard (bifendate). The current UHPLC-MS/MS assay was validated for its linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability in different conditions. The method was linear for all analytes over the investigated range with all determined correlation coefficients exceeding 0.9900. The intra-day and inter-day precisions were in the range of 4.21% to 14.84%, and the relative errors of accuracies were in the range of -14.05% to 14.75%. The mean recoveries and matrix effects of purpurin, munjistin, and mollugin were higher than 78.87% and 92.56%, repectively. After oral administration of 0.82 g/kg of Rubia cordifolia extract, the maximum plasma concentrations (Cmax) were 70.10 +/- 11.78 ng/mL for purpurin, 26.09 +/- 6.6 ng/mL for munjistin, and 52.10 +/- 6.71 ng/mL for mollugin. The time for maximal concentration (Tmax) was 1.61 +/- 0.24 h for purpurin, 2.58 +/- 0.19 h for munjistin, and 1.99 +/- 0.21 h for mollugin. The established method was further applied to a pharmacokinetic study of purpurin, munjistin, and mollugin in rat plasma. It was concluded from the pharmacokinetic parameters that the three analytes showed a process of slow absorption and metabolism after oral administration of R. cordifolia extract to rats. PMID- 27258245 TI - Sorbicillinoids from Fungi and Their Bioactivities. AB - Sorbicillinoids are important hexaketide metabolites derived from fungi. They have a variety of biological activities including cytotoxic, antioxidant, antiviral and antimicrobial activity. The unique structural features of the sorbicillinoids make them attractive candidates for developing new pharmaceutical and agrochemical agents. About 90 sorbicillinoids have been reported in the past few decades. This mini-review aims to briefly summarize their occurrence, structures, and biological activities. PMID- 27258246 TI - Extraction, Purification and Primary Characterization of Polysaccharides from Defatted Peanut (Arachis hypogaea) Cakes. AB - The hot-water extraction, purification and characterization of polysaccharides from defatted peanut cake (PPC) were investigated in this study. A Box-Behnken factorial design (BBD) was used to investigate the effects of three independent variables, namely extraction temperature (X1), extraction time (X2) and ratio of water to raw material (X3). The optimum conditions were 85 degrees C, 3 h and 20:1 (mL/g) respectively. Regression analysis was done to reveal the experimental results which include 34.97% extraction rate while the value verified under these conditions was 34.49%. The crude PPC was sequentially further purified by Sephadex G-100 chromatography, and one purified fraction was obtained. The PPC purified fraction was characterized by FT-IR, HPAEC; SEC-MALLS. The average molecular weight of the PPC purified fraction was 2.383 * 105 Da. The polysaccharide was mainly composed of glucose, galactose, arabinose and xylose. The PPC have the typical absorption of polysaccharide. PMID- 27258247 TI - Coffee Silverskin Extract Protects against Accelerated Aging Caused by Oxidative Agents. AB - Nowadays, coffee beans are almost exclusively used for the preparation of the beverage. The sustainability of coffee production can be achieved introducing new applications for the valorization of coffee by-products. Coffee silverskin is the by-product generated during roasting, and because of its powerful antioxidant capacity, coffee silverskin aqueous extract (CSE) may be used for other applications, such as antiaging cosmetics and dermaceutics. This study aims to contribute to the coffee sector's sustainability through the application of CSE to preserve skin health. Preclinical data regarding the antiaging properties of CSE employing human keratinocytes and Caenorhabditis elegans are collected during the present study. Accelerated aging was induced by tert-butyl hydroperoxide (t BOOH) in HaCaT cells and by ultraviolet radiation C (UVC) in C. elegans. Results suggest that the tested concentrations of coffee extracts were not cytotoxic, and CSE 1 mg/mL gave resistance to skin cells when oxidative damage was induced by t BOOH. On the other hand, nematodes treated with CSE (1 mg/mL) showed a significant increased longevity compared to those cultured on a standard diet. In conclusion, our results support the antiaging properties of the CSE and its great potential for improving skin health due to its antioxidant character associated with phenols among other bioactive compounds present in the botanical material. PMID- 27258248 TI - Hydrogen Bonding: Between Strengthening the Crystal Packing and Improving Solubility of Three Haloperidol Derivatives. AB - The purpose of this study is to confirm the impact of polar functional groups on inter and intra-molecular hydrogen bonding in haloperidol (HP) and droperidol (DP) and, hence, their effects on dissolution using a new approach. To confirm our theory, a new molecule: deshydroxy-haloperidol (DHP) was designed and its synthesis was requested from a contract laboratory. The molecule was then studied and compared to DP and HP. Unlike DHP, both the HP and DP molecules have hydrogen donor groups, therefore, DHP was used to confirm the relative effects of the hydrogen donor group on solubility and crystal packing. The solid dispersions of the three structurally related molecules: HP, DP, and DHP were prepared using PVPK30, and characterized using XRPD and IR. A comparative dissolution study was carried out in aqueous medium. The absence of a hydrogen bonding donor group in DHP resulted in an unexpected increase in its aqueous solubility and dissolution rate from solid dispersion, which is attributed to weaker crystal pack. The increased dissolution rate of HP and DP from solid dispersions is attributed to drug-polymer hydrogen bonding that interferes with the drug-drug intermolecular hydrogen bonding and provides thermodynamic stability of the dispersed drug molecules. The drug-drug intermolecular hydrogen bond is the driving force for precipitation and crystal packing. PMID- 27258249 TI - Effects of a Bovine Lactoferrin Formulation from Cow's Milk on Menstrual Distress in Volunteers: A Randomized, Crossover Study. AB - Dysmenorrhea is a highly prevalent complaint and highly undiagnosed gynecologic condition. Dairy products have a potential in the management of menstrual distress, and bovine lactoferrin can help the subjective dysphoria associated with dysmenorrhea. In the present study, we aimed to investigate the effects of a lactoferrin formulation isolated from cow's milk on menstrual symptoms in volunteers. A double-blind, randomized, placebo-controlled, crossover study of the iron-lactoferrin complex (FeLf) was performed in thirty-five healthy Japanese women. Participants received the 150 mg FeLf (per day) or placebo from day ten of the luteal phase to day four of the follicular phase. The Moos Menstrual Distress Questionnaire (MDQ) was measured for menstrual distress, and heart rate variability was measured as an index of autonomic nerve balance during menses. A visual analog scale for menstrual pain, and a verbal rating scale for quality of life during the first three days of menstruation were measured. The MDQ score for the automatic nervous system subscale was lower and the parasympathetic nervous system activity was greater in FeLf than in placebo for intention-to-treat or per protocol populations. The other variables were not different between the groups. No treatment-related side effects were observed during the study. The results indicate that FeLf can provide a beneficial effect on the psychological symptoms in women affected by menstrual distress. PMID- 27258250 TI - Knockdown of AMPKalpha2 Promotes Pulmonary Arterial Smooth Muscle Cells Proliferation via mTOR/Skp2/p27(Kip1) Signaling Pathway. AB - It has been shown that activation of adenosine monophosphate-activated protein kinase (AMPK) suppresses proliferation of a variety of tumor cells as well as nonmalignant cells. In this study, we used post-transcriptional gene silencing with small interfering RNA (siRNA) to specifically examine the effect of AMPK on pulmonary arterial smooth muscle cells (PASMCs) proliferation and to further elucidate its underlying molecular mechanisms. Our results showed that knockdown of AMPKalpha2 promoted primary cultured PASMCs proliferation; this was accompanied with the elevation of phosphorylation of mammalian target of rapamycin (mTOR) and S-phase kinase-associated protein 2 (Skp2) protein level and reduction of p27(Kip1). Importantly, prior silencing of mTOR with siRNA abolished AMPKalpha2 knockdown-induced Skp2 upregulation, p27(Kip1) reduction as well as PASMCs proliferation. Furthermore, pre-depletion of Skp2 by siRNA also eliminated p27(Kip1) downregulation and PASMCs proliferation caused by AMPKalpha2 knockdown. Taken together, our study indicates that AMPKalpha2 isoform plays an important role in regulation of PASMCs proliferation by modulating mTOR/Skp2/p27(Kip1) axis, and suggests that activation of AMPKalpha2 might have potential value in the prevention and treatment of pulmonary arterial hypertension. PMID- 27258252 TI - Pesticides Drive Stochastic Changes in the Chemoreception and Neurotransmission System of Marine Ectoparasites. AB - Scientific efforts to elucidate the mechanisms of chemical communication between organisms in marine environments are increasing. This study applied novel molecular technology to outline the effects of two xenobiotic drugs, deltamethrin (DM) and azamethiphos (AZA), on the neurotransmission system of the copepod ectoparasite Caligus rogercresseyi. Transcriptome sequencing and bioinformatics analyses were conducted to evaluate treatment effects on the glutamatergic synaptic pathway of the parasite, which is closely related to chemoreception and neurotransmission. After drug treatment with DM or AZA, stochastic mRNA expression patterns of glutamatergic synapse pathway components were observed. Both DM and AZA promoted a down-regulation of the glutamate-ammonia ligase, and DM activated a metabotropic glutamate receptor that is a suggested inhibitor of neurotransmission. Furthermore, the delousing drugs drove complex rearrangements in the distribution of mapped reads for specific metabotropic glutamate receptor domains. This study introduces a novel methodological approach that produces high quality results from transcriptomic data. Using this approach, DM and AZA were found to alter the expression of numerous mRNAs tightly linked to the glutamatergic signaling pathway. These data suggest possible new targets for xenobiotic drugs that play key roles in the delousing effects of antiparasitics in sea lice. PMID- 27258251 TI - Nutraceutical Properties of Olive Oil Polyphenols. An Itinerary from Cultured Cells through Animal Models to Humans. AB - The increasing interest in the Mediterranean diet hinges on its healthy and anti ageing properties. The composition of fatty acids, vitamins and polyphenols in olive oil, a key component of this diet, is considered a key feature of its healthy properties. Therefore, it is of significance that the Rod of Asclepius lying on a world map surrounded by olive tree branches has been chosen by the World Health Organization as a symbol of both peace and well-being. This review travels through most of the current and past research, recapitulating the biochemical and physiological correlations of the beneficial properties of olive tree (Olea europaea) polyphenols and their derivatives found in olive oil. The factors influencing the content and beneficial properties of olive oil polyphenols will also be taken into account together with their bioavailability. Finally, the data on the clinical and epidemiological relevance of olive oil and its polyphenols for longevity and against age- and lifestyle-associated pathologies such as cancer, cardiovascular, metabolic and neurodegenerative diseases are reviewed. PMID- 27258253 TI - Targeting DNA Damage Response in the Radio(Chemo)therapy of Non-Small Cell Lung Cancer. AB - Lung cancer is the leading cause of cancer death worldwide due to its high incidence and mortality. As the most common lung cancer, non-small cell lung cancer (NSCLC) is a terrible threat to human health. Despite improvements in diagnosis and combined treatments including surgical resection, radiotherapy and chemotherapy, the overall survival for NSCLC patients still remains poor. DNA damage is considered to be the primary cause of lung cancer development and is normally recognized and repaired by the intrinsic DNA damage response machinery. The role of DNA repair pathways in radio(chemo)therapy-resistant cancers has become an area of significant interest in the clinical setting. Meanwhile, some studies have proved that genetic and epigenetic factors can alter the DNA damage response and repair, which results in changes of the radiation and chemotherapy curative effect in NSCLC. In this review, we focus on the effect of genetic polymorphisms and epigenetic factors such as miRNA regulation and lncRNA regulation participating in DNA damage repair in response to radio(chemo)therapy in NSCLC. These may provide novel information on the radio(chemo)therapy of NSCLC based on the individual DNA damage response. PMID- 27258254 TI - Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish. AB - A sizeable portion of the societal drain from cocaine abuse results from the complications of in utero drug exposure. Because of challenges in using humans and mammalian model organisms as test subjects, much debate remains about the impact of in utero cocaine exposure. Zebrafish offer a number of advantages as a model in longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to cocaine on development and on subsequent cardiovascular physiology and cocaine-induced conditioned place preference (CPP) in longitudinal adults. Larval fish showed a progressive decrease in telencephalic size with increased doses of cocaine. These treated larvae also showed a dose dependent response in heart rate that persisted 24 h after drug cessation. Embryonic cocaine exposure had little effect on overall health of longitudinal adults, but subtle changes in cardiovascular physiology were seen including decreased sensitivity to isoproterenol and increased sensitivity to cocaine. These longitudinal adult fish also showed an embryonic dose-dependent change in CPP behavior, suggesting an increased sensitivity. These studies clearly show that pre-exposure during embryonic development affects subsequent cocaine sensitivity in longitudinal adults. PMID- 27258256 TI - Comparative Mitogenomic Analysis of Species Representing Six Subfamilies in the Family Tenebrionidae. AB - To better understand the architecture and evolution of the mitochondrial genome (mitogenome), mitogenomes of ten specimens representing six subfamilies in Tenebrionidae were selected, and comparative analysis of these mitogenomes was carried out in this study. Ten mitogenomes in this family share a similar gene composition, gene order, nucleotide composition, and codon usage. In addition, our results show that nucleotide bias was strongly influenced by the preference of codon usage for A/T rich codons which significantly correlated with the G + C content of protein coding genes (PCGs). Evolutionary rate analyses reveal that all PCGs have been subjected to a purifying selection, whereas 13 PCGs displayed different evolution rates, among which ATPase subunit 8 (ATP8) showed the highest evolutionary rate. We inferred the secondary structure for all RNA genes of Tenebrio molitor (Te2) and used this as the basis for comparison with the same genes from other Tenebrionidae mitogenomes. Some conserved helices (stems) and loops of RNA structures were found in different domains of ribosomal RNAs (rRNAs) and the cloverleaf structure of transfer RNAs (tRNAs). With regard to the AT-rich region, we analyzed tandem repeat sequences located in this region and identified some essential elements including T stretches, the consensus motif at the flanking regions of T stretch, and the secondary structure formed by the motif at the 3' end of T stretch in major strand, which are highly conserved in these species. Furthermore, phylogenetic analyses using mitogenomic data strongly support the relationships among six subfamilies: ((Tenebrionidae incertae sedis + (Diaperinae + Tenebrioninae)) + (Pimeliinae + Lagriinae)), which is consistent with phylogenetic results based on morphological traits. PMID- 27258255 TI - The Transcription Factor OsWRKY45 Negatively Modulates the Resistance of Rice to the Brown Planthopper Nilaparvata lugens. AB - WRKY transcription factors play a central role not only in plant growth and development but also in plant stress responses. However, the role of WRKY transcription factors in herbivore-induced plant defenses and their underlying mechanisms, especially in rice, remains largely unclear. Here, we cloned a rice WRKY gene OsWRKY45, whose expression was induced by mechanical wounding, by infestation of the brown planthopper (BPH, Nilaparvata lugens) and by treatment with jasmonic acid (JA) or salicylic acid (SA). The antisense expression of OsWRKY45 (as-wrky) enhanced BPH-induced levels of H2O2 and ethylene, reduced feeding and oviposition preference as well as the survival rate of BPH, and delayed the development of BPH nymphs. Consistently, lower population densities of BPH on as-wrky lines, compared to those on wild-type (WT) plants, were observed in field experiments. On the other hand, as-wrky lines in the field had lower susceptibility to sheath blight (caused by Rhizoctonia solani) but higher susceptibility to rice blast (caused by Magnaporthe oryzae) than did WT plants. These findings suggest that OsWRKY45 plays important but contrasting roles in regulating the resistance of rice to pathogens and herbivores, and attention should be paid if OsWRKY45 is used to develop disease or herbivore-resistant rice. PMID- 27258257 TI - miR-218 Involvement in Cardiomyocyte Hypertrophy Is Likely through Targeting REST. AB - MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with significant risks of heart failure. However, many microRNAs are still not recognized for their functions in pathophysiological processes. In this study, we evaluated effects of miR-218 in cardiomyocyte hypertrophy using both in vitro and in vivo models. We found that miR-218 was evidently downregulated in a transverse aortic constriction (TAC) mouse model. Overexpression of miR-218 is sufficient to reduce hypertrophy, whereas the suppression of miR-218 aggravates hypertrophy in primary cardiomyocytes induced by isoprenaline (ISO). In addition, we identified RE1 silencing transcription factor (REST) as a novel target of miR-218; it negatively regulated the expression of REST in hypertrophic cardiomyocytes and the TAC model. These results showed that miR-218 plays a crucial role in cardiomyocyte hypertrophy, likely via targeting REST, suggesting a potential candidate target for interfering hypertrophy. PMID- 27258258 TI - Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis. AB - Acute osteomyelitis and septic arthritis are two infections whose frequencies are increasing in pediatric patients. Acute osteomyelitis and septic arthritis need to be carefully assessed, diagnosed, and treated to avoid devastating sequelae. Traditionally, the treatment of acute osteoarticular infection in pediatrics was based on prolonged intravenous anti-infective therapy. However, results from clinical trials have suggested that in uncomplicated cases, a short course of a few days of parenteral antibiotics followed by oral therapy is safe and effective. The aim of this review is to provide clinicians an update on recent controversies and advances regarding the management of acute osteomyelitis and septic arthritis in children. In recent years, the emergence of bacterial species resistant to commonly used antibiotics that are particularly aggressive highlights the necessity for further research to optimize treatment approaches and to develop new molecules able to fight the war against acute osteoarticular infection in pediatric patients. PMID- 27258259 TI - Role of Hedgehog Signaling Pathway in NASH. AB - Non-alcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease in the Western world. Although only a minority of patients will ultimately develop end-stage liver disease, it is not yet possible to efficiently predict who will progress and, most importantly, effective treatments are still unavailable. Better understanding of the pathophysiology of this disease is necessary to improve the clinical management of NAFLD patients. Epidemiological data indicate that NAFLD prognosis is determined by an individual's response to lipotoxic injury, rather than either the severity of exposure to lipotoxins, or the intensity of liver injury. The liver responds to injury with a synchronized wound-healing response. When this response is abnormal, it leads to pathological scarring, resulting in progressive fibrosis and cirrhosis, rather than repair. The hedgehog pathway is a crucial player in the wound-healing response. In this review, we summarize the pre-clinical and clinical evidence, which demonstrate the role of hedgehog pathway dysregulation in NAFLD pathogenesis, and the preliminary data that place the hedgehog pathway as a potential target for the treatment of this disease. PMID- 27258261 TI - Changes in the Arabidopsis thaliana Proteome Implicate cAMP in Biotic and Abiotic Stress Responses and Changes in Energy Metabolism. AB - The second messenger 3',5'-cyclic adenosine monophosphate (cAMP) is increasingly recognized as having many different roles in plant responses to environmental stimuli. To gain further insights into these roles, Arabidopsis thaliana cell suspension culture was treated with 100 nM of cell permeant 8-bromo-cAMP for 5 or 10 min. Here, applying mass spectrometry and comparative proteomics, 20 proteins were identified as differentially expressed and we noted a specific bias in proteins with a role in abiotic stress, particularly cold and salinity, biotic stress as well as proteins with a role in glycolysis. These findings suggest that cAMP is sufficient to elicit specific stress responses that may in turn induce complex changes to cellular energy homeostasis. PMID- 27258260 TI - DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer Comorbidity and Beyond. AB - Schizophrenia and autism spectrum disorder (ASD) are multi-factorial and multi symptomatic psychiatric disorders, each affecting 0.5%-1% of the population worldwide. Both are characterized by impairments in cognitive functions, emotions and behaviour, and they undermine basic human processes of perception and judgment. Despite decades of extensive research, the aetiologies of schizophrenia and ASD are still poorly understood and remain a significant challenge to clinicians and scientists alike. Adding to this unsatisfactory situation, patients with schizophrenia or ASD often develop a variety of peripheral and systemic disturbances, one prominent example of which is cancer, which shows a direct (but sometimes inverse) comorbidity in people affected with schizophrenia and ASD. Cancer is a disease characterized by uncontrolled proliferation of cells, the molecular origin of which derives from mutations of a cell's DNA sequence. To counteract such mutations and repair damaged DNA, cells are equipped with intricate DNA repair pathways. Oxidative stress, oxidative DNA damage, and deficient repair of oxidative DNA lesions repair have been proposed to contribute to the development of schizophrenia and ASD. In this article, we summarize the current evidence of cancer comorbidity in these brain disorders and discuss the putative roles of oxidative stress, DNA damage and DNA repair in the aetiopathology of schizophrenia and ASD. PMID- 27258262 TI - Identification of Protein-Excipient Interaction Hotspots Using Computational Approaches. AB - Protein formulation development relies on the selection of excipients that inhibit protein-protein interactions preventing aggregation. Empirical strategies involve screening many excipient and buffer combinations using force degradation studies. Such methods do not readily provide information on intermolecular interactions responsible for the protective effects of excipients. This study describes a molecular docking approach to screen and rank interactions allowing for the identification of protein-excipient hotspots to aid in the selection of excipients to be experimentally screened. Previously published work with Drosophila Su(dx) was used to develop and validate the computational methodology, which was then used to determine the formulation hotspots for Fab A33. Commonly used excipients were examined and compared to the regions in Fab A33 prone to protein-protein interactions that could lead to aggregation. This approach could provide information on a molecular level about the protective interactions of excipients in protein formulations to aid the more rational development of future formulations. PMID- 27258264 TI - Influence of Ionic Liquids on an Iron(III) Catalyzed Three-Component Coupling/Hydroarylation/Dehydrogenation Tandem Reaction. AB - A three-component oxidative dehydrogenation tandem reaction via the coupling and hydroarylation of benzaldehyde, aniline and phenylacetylene to a quinoline derivate was catalyzed by an iron-containing ionic liquid. The reaction was air mediated and could be performed under neat conditions. The iron(III) of the ionic liquid was the oxidizing species. PMID- 27258265 TI - Home-Processed Red Beetroot (Beta vulgaris L.) Products: Changes in Antioxidant Properties and Bioaccessibility. AB - In this study, the effects of home-processing on the antioxidant properties and in vitro bioaccessibility of red beetroot bioactives were investigated. For this purpose, fresh red beetroot and six different home-processed red beetroot products-including boiled, oven-dried, pickled, pureed, juice-processed, and jam processed-were analyzed and compared for their total phenolic (TP) and total flavonoid (TF) contents, total antioxidant capacities (TAC), and individual anthocyanin contents. In addition, bioaccessibility of red beetroot antioxidants was determined using an in vitro simulated gastrointestinal digestion method. Dried, pureed, and fresh red beetroot samples had the highest TP, TF, and TAC values, which were 347 +/- 23 mg gallic acid equivalent (GAE)/100 g, 289 +/- 53 mg rutin equivalent (RE)/100 g, 3889 +/- 982 mg trolox equivalent antioxidant capacity (TEAC)/100 g, respectively. The in vitro digestion method revealed the highest recovery for TP (16%) and TAC (1.3%) in jam. This study provides comparative data to evaluate the effects of various home-processing techniques on antioxidant potential of red beetroot products. PMID- 27258263 TI - Activation of DNA Damage Response Induced by the Kaposi's Sarcoma-Associated Herpes Virus. AB - The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman's disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form. However, in a limited number of cells, it undergoes spontaneous lytic reactivation to ensure the production of new virions. During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. This review will focus on the interplay between the KSHV and the DDR response pathway throughout the viral lifecycle, exploring the putative molecular mechanism/s that may contribute to malignant transformation of host cells. PMID- 27258267 TI - Stable Toll-Like Receptor 10 Knockdown in THP-1 Cells Reduces TLR-Ligand-Induced Proinflammatory Cytokine Expression. AB - Toll-like receptor 10 (TLR10) is the only orphan receptor whose natural ligand and function are unknown among the 10 human TLRs. In this study, to test whether TLR10 recognizes some known TLR ligands, we established a stable TLR10 knockdown human monocytic cell line THP-1 using TLR10 short hairpin RNA lentiviral particle and puromycin selection. Among 60 TLR10 knockdown clones that were derived from each single transduced cell, six clones were randomly selected, and then one of those clones, named E7, was chosen for the functional study. E7 exhibited approximately 50% inhibition of TLR10 mRNA and protein expression. Of all the TLRs, only the expression of TLR10 changed significantly in this cell line. Additionally, phorbol 12-myristate 13-acetate-induced macrophage differentiation of TLR10 knockdown cells was not affected in the knockdown cells. When exposed to TLR ligands, such as synthetic diacylated lipoprotein (FSL-1), lipopolysaccharide (LPS), and flagellin, significant induction of proinflammatory cytokine gene expression including Interleukin-8 (IL-8), Interleukin-1 beta (IL-1beta), Tumor necrosis factor-alpha (TNF-alpha) and Chemokine (C-C Motif) Ligand 20 (CCL20) expression, was found in the control THP-1 cells, whereas the TLR10 knockdown cells exhibited a significant reduction in the expression of IL-8, IL-1beta, and CCL20. TNF-alpha was the only cytokine for which the expression did not decrease in the TLR10 knockdown cells from that measured in the control cells. Analysis of putative binding sites for transcription factors using a binding-site-prediction program revealed that the TNF-alpha promoter does not have putative binding sites for AP-1 or c-Jun, comprising a major transcription factor along with NF-kappaB for TLR signaling. Our results suggest that TLR10 is involved in the recognition of FSL-1, LPS, and flagellin and TLR-ligand-induced expression of TNF-alpha does not depend on TLR10. PMID- 27258266 TI - Plant Metabolomics: An Indispensable System Biology Tool for Plant Science. AB - As genomes of many plant species have been sequenced, demand for functional genomics has dramatically accelerated the improvement of other omics including metabolomics. Despite a large amount of metabolites still remaining to be identified, metabolomics has contributed significantly not only to the understanding of plant physiology and biology from the view of small chemical molecules that reflect the end point of biological activities, but also in past decades to the attempts to improve plant behavior under both normal and stressed conditions. Hereby, we summarize the current knowledge on the genetic and biochemical mechanisms underlying plant growth, development, and stress responses, focusing further on the contributions of metabolomics to practical applications in crop quality improvement and food safety assessment, as well as plant metabolic engineering. We also highlight the current challenges and future perspectives in this inspiring area, with the aim to stimulate further studies leading to better crop improvement of yield and quality. PMID- 27258268 TI - Aquaporin-11 (AQP11) Expression in the Mouse Brain. AB - Aquaporin-11 (AQP11) is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA) and protein were expressed in the brain, but much less than in the thymus and kidney. Immunostaining showed that AQP11 was localized at the epithelium of the choroid plexus and at the endothelium of the brain capillary, suggesting that AQP11 may be involved in water transport at the choroid plexus and blood-brain barrier (BBB) in the brain. The expression of AQP4, another brain AQP expressed at the BBB, was decreased by half in AQP11 deficient mice, thereby suggesting the presence of the interaction between AQP11 and AQP4. The brain of AQP11-deficient mice, however, did not show any morphological abnormalities and the function of the BBB was intact. Our findings provide a novel insight into a water transport mechanism mediated by AQPs in the brain, which may lead to a new therapy for brain edema. PMID- 27258270 TI - Probabilistic Assessment of High-Throughput Wireless Sensor Networks. AB - Structural health monitoring (SHM) using wireless smart sensors (WSS) has the potential to provide rich information on the state of a structure. However, because of their distributed nature, maintaining highly robust and reliable networks can be challenging. Assessing WSS network communication quality before and after finalizing a deployment is critical to achieve a successful WSS network for SHM purposes. Early studies on WSS network reliability mostly used temporal signal indicators, composed of a smaller number of packets, to assess the network reliability. However, because the WSS networks for SHM purpose often require high data throughput, i.e., a larger number of packets are delivered within the communication, such an approach is not sufficient. Instead, in this study, a model that can assess, probabilistically, the long-term performance of the network is proposed. The proposed model is based on readily-available measured data sets that represent communication quality during high-throughput data transfer. Then, an empirical limit-state function is determined, which is further used to estimate the probability of network communication failure. Monte Carlo simulation is adopted in this paper and applied to a small and a full-bridge wireless networks. By performing the proposed analysis in complex sensor networks, an optimized sensor topology can be achieved. PMID- 27258269 TI - Review on Graph Clustering and Subgraph Similarity Based Analysis of Neurological Disorders. AB - How can complex relationships among molecular or clinico-pathological entities of neurological disorders be represented and analyzed? Graphs seem to be the current answer to the question no matter the type of information: molecular data, brain images or neural signals. We review a wide spectrum of graph representation and graph analysis methods and their application in the study of both the genomic level and the phenotypic level of the neurological disorder. We find numerous research works that create, process and analyze graphs formed from one or a few data types to gain an understanding of specific aspects of the neurological disorders. Furthermore, with the increasing number of data of various types becoming available for neurological disorders, we find that integrative analysis approaches that combine several types of data are being recognized as a way to gain a global understanding of the diseases. Although there are still not many integrative analyses of graphs due to the complexity in analysis, multi-layer graph analysis is a promising framework that can incorporate various data types. We describe and discuss the benefits of the multi-layer graph framework for studies of neurological disease. PMID- 27258271 TI - Two-Dimensional DOA and Polarization Estimation for a Mixture of Uncorrelated and Coherent Sources with Sparsely-Distributed Vector Sensor Array. AB - This paper presents an L-shaped sparsely-distributed vector sensor (SD-VS) array with four different antenna compositions. With the proposed SD-VS array, a novel two-dimensional (2-D) direction of arrival (DOA) and polarization estimation method is proposed to handle the scenario where uncorrelated and coherent sources coexist. The uncorrelated and coherent sources are separated based on the moduli of the eigenvalues. For the uncorrelated sources, coarse estimates are acquired by extracting the DOA information embedded in the steering vectors from estimated array response matrix of the uncorrelated sources, and they serve as coarse references to disambiguate fine estimates with cyclical ambiguity obtained from the spatial phase factors. For the coherent sources, four Hankel matrices are constructed, with which the coherent sources are resolved in a similar way as for the uncorrelated sources. The proposed SD-VS array requires only two collocated antennas for each vector sensor, thus the mutual coupling effects across the collocated antennas are reduced greatly. Moreover, the inter-sensor spacings are allowed beyond a half-wavelength, which results in an extended array aperture. Simulation results demonstrate the effectiveness and favorable performance of the proposed method. PMID- 27258272 TI - Blind RSSD-Based Indoor Localization with Confidence Calibration and Energy Control. AB - Indoor localization based on wireless sensor networks (WSNs) is an important field of research with numerous applications, such as elderly care, miner security, and smart buildings. In this paper, we present a localization method based on the received signal strength difference (RSSD) to determine a target on a map with unknown transmission information. To increase the accuracy of localization, we propose a confidence value for each anchor node to indicate its credibility for participating in the estimation. An automatic calibration device is designed to help acquire the values. The acceleration sensor and unscented Kalman filter (UKF) are also introduced to reduce the influence of measuring noise in the application. Energy control is another key point in WSN systems and may prolong the lifetime of the system. Thus, a quadtree structure is constructed to describe the region correlation between neighboring areas, and the unnecessary anchor nodes can be detected and set to sleep to save energy. The localization system is implemented on real-time Texas Instruments CC2430 and CC2431 embedded platforms, and the experimental results indicate that these mechanisms achieve a high accuracy and low energy cost. PMID- 27258273 TI - A Highly Sensitive Fiber-Optic Fabry-Perot Interferometer Based on Internal Reflection Mirrors for Refractive Index Measurement. AB - In this study, a new type of highly sensitive fiber-optic Fabry-Perot interferometer (FFPI) is proposed with a high sensitivity on a wide refractive index (RI) measurement range based on internal reflection mirrors of micro cavity. The sensor head consists of a single-mode fiber (SMF) with an open micro cavity. Since light reflections of gold thin films are not affected by the RI of different measuring mediums, the sensor is designed to improve the fringe visibility of optical interference through sputtering the gold films of various thicknesses on the inner surfaces of the micro-cavity, as a semi-transparent mirror (STM) and a total-reflection mirror (TRM). Experiments have been carried out to verify the feasibility of the sensor's design. It is shown that the fabricated sensor has strong interference visibility exceeding 15 dB over a wide measurement range of RI, and the sensor sensitivity is higher than 1160 nm/RIU, and RI resolution is better than 1.0 * 10(-6) RIU. PMID- 27258274 TI - Power Pattern Sensitivity to Calibration Errors and Mutual Coupling in Linear Arrays through Circular Interval Arithmetics. AB - The sensitivity to both calibration errors and mutual coupling effects of the power pattern radiated by a linear array is addressed. Starting from the knowledge of the nominal excitations of the array elements and the maximum uncertainty on their amplitudes, the bounds of the pattern deviations from the ideal one are analytically derived by exploiting the Circular Interval Analysis (CIA). A set of representative numerical results is reported and discussed to assess the effectiveness and the reliability of the proposed approach also in comparison with state-of-the-art methods and full-wave simulations. PMID- 27258275 TI - Characterisation of Phosphate Accumulating Organisms and Techniques for Polyphosphate Detection: A Review. AB - Phosphate minerals have long been used for the production of phosphorus-based chemicals used in many economic sectors. However, these resources are not renewable and the natural phosphate stocks are decreasing. In this context, the research of new phosphate sources has become necessary. Many types of wastes contain non-negligible phosphate concentrations, such as wastewater. In wastewater treatment plants, phosphorus is eliminated by physicochemical and/or biological techniques. In this latter case, a specific microbiota, phosphate accumulating organisms (PAOs), accumulates phosphate as polyphosphate. This molecule can be considered as an alternative phosphate source, and is directly extracted from wastewater generated by human activities. This review focuses on the techniques which can be applied to enrich and try to isolate these PAOs, and to detect the presence of polyphosphate in microbial cells. PMID- 27258276 TI - A Noise Reduction Method for Dual-Mass Micro-Electromechanical Gyroscopes Based on Sample Entropy Empirical Mode Decomposition and Time-Frequency Peak Filtering. AB - The different noise components in a dual-mass micro-electromechanical system (MEMS) gyroscope structure is analyzed in this paper, including mechanical thermal noise (MTN), electronic-thermal noise (ETN), flicker noise (FN) and Coriolis signal in-phase noise (IPN). The structure equivalent electronic model is established, and an improved white Gaussian noise reduction method for dual mass MEMS gyroscopes is proposed which is based on sample entropy empirical mode decomposition (SEEMD) and time-frequency peak filtering (TFPF). There is a contradiction in TFPS, i.e., selecting a short window length may lead to good preservation of signal amplitude but bad random noise reduction, whereas selecting a long window length may lead to serious attenuation of the signal amplitude but effective random noise reduction. In order to achieve a good tradeoff between valid signal amplitude preservation and random noise reduction, SEEMD is adopted to improve TFPF. Firstly, the original signal is decomposed into intrinsic mode functions (IMFs) by EMD, and the SE of each IMF is calculated in order to classify the numerous IMFs into three different components; then short window TFPF is employed for low frequency component of IMFs, and long window TFPF is employed for high frequency component of IMFs, and the noise component of IMFs is wiped off directly; at last the final signal is obtained after reconstruction. Rotation experimental and temperature experimental are carried out to verify the proposed SEEMD-TFPF algorithm, the verification and comparison results show that the de-noising performance of SEEMD-TFPF is better than that achievable with the traditional wavelet, Kalman filter and fixed window length TFPF methods. PMID- 27258277 TI - Tool Condition Monitoring and Remaining Useful Life Prognostic Based on a Wireless Sensor in Dry Milling Operations. AB - Tool breakage causes losses of surface polishing and dimensional accuracy for machined part, or possible damage to a workpiece or machine. Tool Condition Monitoring (TCM) is considerably vital in the manufacturing industry. In this paper, an indirect TCM approach is introduced with a wireless triaxial accelerometer. The vibrations in the three vertical directions (x, y and z) are acquired during milling operations, and the raw signals are de-noised by wavelet analysis. These features of de-noised signals are extracted in the time, frequency and time-frequency domains. The key features are selected based on Pearson's Correlation Coefficient (PCC). The Neuro-Fuzzy Network (NFN) is adopted to predict the tool wear and Remaining Useful Life (RUL). In comparison with Back Propagation Neural Network (BPNN) and Radial Basis Function Network (RBFN), the results show that the NFN has the best performance in the prediction of tool wear and RUL. PMID- 27258278 TI - Use of a Force-Torque Sensor for Self-Calibration of a 6-DOF Medical Robot. AB - The aim of this paper is to improve the position accuracy of a six degree of freedom medical robot. The improvement in accuracy is achieved without the use of any external measurement device. Instead, this work presents a novel calibration approach based on using an embedded force-torque sensor to identify the robot's kinematic parameters and thereby enhance the positioning accuracy. A simulation study demonstrated that our calibration approach is effective, whether or not any measurement noise is present: the position error is improved, inside the robot target workspace, from 12 mm to 0.320 mm, for the maximum values, and from 9 mm to 0.2771 mm, for the mean errors. PMID- 27258279 TI - Robust Statistical Approaches for RSS-Based Floor Detection in Indoor Localization. AB - Floor detection for indoor 3D localization of mobile devices is currently an important challenge in the wireless world. Many approaches currently exist, but usually the robustness of such approaches is not addressed or investigated. The goal of this paper is to show how to robustify the floor estimation when probabilistic approaches with a low number of parameters are employed. Indeed, such an approach would allow a building-independent estimation and a lower computing power at the mobile side. Four robustified algorithms are to be presented: a robust weighted centroid localization method, a robust linear trilateration method, a robust nonlinear trilateration method, and a robust deconvolution method. The proposed approaches use the received signal strengths (RSS) measured by the Mobile Station (MS) from various heard WiFi access points (APs) and provide an estimate of the vertical position of the MS, which can be used for floor detection. We will show that robustification can indeed increase the performance of the RSS-based floor detection algorithms. PMID- 27258280 TI - NetCoDer: A Retransmission Mechanism for WSNs Based on Cooperative Relays and Network Coding. AB - Some of the most difficult problems to deal with when using Wireless Sensor Networks (WSNs) are related to the unreliable nature of communication channels. In this context, the use of cooperative diversity techniques and the application of network coding concepts may be promising solutions to improve the communication reliability. In this paper, we propose the NetCoDer scheme to address this problem. Its design is based on merging cooperative diversity techniques and network coding concepts. We evaluate the effectiveness of the NetCoDer scheme through both an experimental setup with real WSN nodes and a simulation assessment, comparing NetCoDer performance against state-of-the-art TDMA-based (Time Division Multiple Access) retransmission techniques: BlockACK, Master/Slave and Redundant TDMA. The obtained results highlight that the proposed NetCoDer scheme clearly improves the network performance when compared with other retransmission techniques. PMID- 27258281 TI - Guided-Mode-Leaky-Mode-Guided-Mode Fiber Interferometer and Its High Sensitivity Refractive Index Sensing Technology. AB - A cascaded symmetrical dual-taper Mach-Zehnder interferometer structure based on guided-mode and leaky-mode interference is proposed in this paper. Firstly, the interference spectrum characteristics of interferometer has been analyzed by the Finite Difference-Beam Propagation Method (FD-BPM). When the diameter of taper waist is 20 MUm-30 MUm, dual-taper length is 1 mm and taper distance is 4 cm-6 cm, the spectral contrast is higher, which is suitable for sensing. Secondly, experimental research on refractive index sensitivity is carried out. A refractive index sensitivity of 62.78 nm/RIU (refractive index unit) can achieved in the RI range of 1.3333-1.3792 (0%~25% NaCl solution), when the sensor structure parameters meet the following conditions: diameter of taper waist is 24 MUm, dual-taper length is 837 MUm and taper distance is 5.5 cm. The spectrum contrast is 0.8 and measurement resolution is 1.6 * 10(-5) RIU. The simulation analysis is highly consistent with experimental results. Research shows that the sensor has promising application in low RI fields where high-precision measurement is required due to its high sensitivity and stability. PMID- 27258282 TI - How Accurately Can Your Wrist Device Recognize Daily Activities and Detect Falls? AB - Although wearable accelerometers can successfully recognize activities and detect falls, their adoption in real life is low because users do not want to wear additional devices. A possible solution is an accelerometer inside a wrist device/smartwatch. However, wrist placement might perform poorly in terms of accuracy due to frequent random movements of the hand. In this paper we perform a thorough, large-scale evaluation of methods for activity recognition and fall detection on four datasets. On the first two we showed that the left wrist performs better compared to the dominant right one, and also better compared to the elbow and the chest, but worse compared to the ankle, knee and belt. On the third (Opportunity) dataset, our method outperformed the related work, indicating that our feature-preprocessing creates better input data. And finally, on a real life unlabeled dataset the recognized activities captured the subject's daily rhythm and activities. Our fall-detection method detected all of the fast falls and minimized the false positives, achieving 85% accuracy on the first dataset. Because the other datasets did not contain fall events, only false positives were evaluated, resulting in 9 for the second, 1 for the third and 15 for the real life dataset (57 days data). PMID- 27258283 TI - Overhauser Geomagnetic Sensor Based on the Dynamic Nuclear Polarization Effect for Magnetic Prospecting. AB - Based on the dynamic nuclear polarization (DNP) effect, an alternative design of an Overhauser geomagnetic sensor is presented that enhances the proton polarization and increases the amplitude of the free induction decay (FID) signal. The short-pulse method is adopted to rotate the enhanced proton magnetization into the plane of precession to create an FID signal. To reduce the negative effect of the powerful electromagnetic interference, the design of the anti-interference of the pick-up coil is studied. Furthermore, the radio frequency polarization method based on the capacitive-loaded coaxial cavity is proposed to improve the quality factor of the resonant circuit. In addition, a special test instrument is designed that enables the simultaneous testing of the classical proton precession and the Overhauser sensor. Overall, comparison experiments with and without the free radical of the Overhauser sensors show that the DNP effect does effectively improve the amplitude and quality of the FID signal, and the magnetic sensitivity, resolution and range reach to 10 pT/Hz 1 / 2 @1 Hz, 0.0023 nT and 20-100 MU T, respectively. PMID- 27258284 TI - Reference Device-Assisted Adaptive Location Fingerprinting. AB - Location fingerprinting suffers in dynamic environments and needs recalibration from time to time to maintain system performance. This paper proposes an adaptive approach for location fingerprinting. Based on real-time received signal strength indicator (RSSI) samples measured by a group of reference devices, the approach applies a modified Universal Kriging (UK) interpolant to estimate adaptive temporal and environmental radio maps. The modified UK can take the spatial distribution characteristics of RSSI into account. In addition, the issue of device heterogeneity caused by multiple reference devices is further addressed. To compensate the measuring differences of heterogeneous reference devices, differential RSSI metric is employed. Extensive experiments were conducted in an indoor field and the results demonstrate that the proposed approach not only adapts to dynamic environments and the situation of changing APs' positions, but it is also robust toward measuring differences of heterogeneous reference devices. PMID- 27258285 TI - An Improved Interacting Multiple Model Filtering Algorithm Based on the Cubature Kalman Filter for Maneuvering Target Tracking. AB - In order to improve the tracking accuracy, model estimation accuracy and quick response of multiple model maneuvering target tracking, the interacting multiple models five degree cubature Kalman filter (IMM5CKF) is proposed in this paper. In the proposed algorithm, the interacting multiple models (IMM) algorithm processes all the models through a Markov Chain to simultaneously enhance the model tracking accuracy of target tracking. Then a five degree cubature Kalman filter (5CKF) evaluates the surface integral by a higher but deterministic odd ordered spherical cubature rule to improve the tracking accuracy and the model switch sensitivity of the IMM algorithm. Finally, the simulation results demonstrate that the proposed algorithm exhibits quick and smooth switching when disposing different maneuver models, and it also performs better than the interacting multiple models cubature Kalman filter (IMMCKF), interacting multiple models unscented Kalman filter (IMMUKF), 5CKF and the optimal mode transition matrix IMM (OMTM-IMM). PMID- 27258286 TI - Data-Driven Design of Intelligent Wireless Networks: An Overview and Tutorial. AB - Data science or "data-driven research" is a research approach that uses real-life data to gain insight about the behavior of systems. It enables the analysis of small, simple as well as large and more complex systems in order to assess whether they function according to the intended design and as seen in simulation. Data science approaches have been successfully applied to analyze networked interactions in several research areas such as large-scale social networks, advanced business and healthcare processes. Wireless networks can exhibit unpredictable interactions between algorithms from multiple protocol layers, interactions between multiple devices, and hardware specific influences. These interactions can lead to a difference between real-world functioning and design time functioning. Data science methods can help to detect the actual behavior and possibly help to correct it. Data science is increasingly used in wireless research. To support data-driven research in wireless networks, this paper illustrates the step-by-step methodology that has to be applied to extract knowledge from raw data traces. To this end, the paper (i) clarifies when, why and how to use data science in wireless network research; (ii) provides a generic framework for applying data science in wireless networks; (iii) gives an overview of existing research papers that utilized data science approaches in wireless networks; (iv) illustrates the overall knowledge discovery process through an extensive example in which device types are identified based on their traffic patterns; (v) provides the reader the necessary datasets and scripts to go through the tutorial steps themselves. PMID- 27258287 TI - TripSense: A Trust-Based Vehicular Platoon Crowdsensing Scheme with Privacy Preservation in VANETs. AB - In this paper, we propose a trust-based vehicular platoon crowdsensing scheme, named TripSense, in VANET. The proposed TripSense scheme introduces a trust-based system to evaluate vehicles' sensing abilities and then selects the more capable vehicles in order to improve sensing results accuracy. In addition, the sensing tasks are accomplished by platoon member vehicles and preprocessed by platoon head vehicles before the data are uploaded to server. Hence, it is less time consuming and more efficient compared with the way where the data are submitted by individual platoon member vehicles. Hence it is more suitable in ephemeral networks like VANET. Moreover, our proposed TripSense scheme integrates unlinkable pseudo-ID techniques to achieve PM vehicle identity privacy, and employs a privacy-preserving sensing vehicle selection scheme without involving the PM vehicle's trust score to keep its location privacy. Detailed security analysis shows that our proposed TripSense scheme not only achieves desirable privacy requirements but also resists against attacks launched by adversaries. In addition, extensive simulations are conducted to show the correctness and effectiveness of our proposed scheme. PMID- 27258288 TI - An Exact Formula for Calculating Inverse Radial Lens Distortions. AB - This article presents a new approach to calculating the inverse of radial distortions. The method presented here provides a model of reverse radial distortion, currently modeled by a polynomial expression, that proposes another polynomial expression where the new coefficients are a function of the original ones. After describing the state of the art, the proposed method is developed. It is based on a formal calculus involving a power series used to deduce a recursive formula for the new coefficients. We present several implementations of this method and describe the experiments conducted to assess the validity of the new approach. Such an approach, non-iterative, using another polynomial expression, able to be deduced from the first one, can actually be interesting in terms of performance, reuse of existing software, or bridging between different existing software tools that do not consider distortion from the same point of view. PMID- 27258289 TI - Biosynthetic Functional Gene Analysis of Bis-Indole Metabolites from 25D7, a Clone Derived from a Deep-Sea Sediment Metagenomic Library. AB - This work investigated the metabolites and their biosynthetic functional hydroxylase genes of the deep-sea sediment metagenomic clone 25D7. 5-Bromoindole was added to the 25D7 clone derived Escherichia coli fermentation broth. The new generated metabolites and their biosynthetic byproducts were located through LC MS, in which the isotope peaks of brominated products emerged. Two new brominated bis-indole metabolites, 5-bromometagenediindole B (1), and 5 bromometagenediindole C (2) were separated under the guidance of LC-MS. Their structures were elucidated on the basis of 1D and 2D NMR spectra (COSY, HSQC, and HMBC). The biosynthetic functional genes of the two new compounds were revealed through LC-MS and transposon mutagenesis analysis. 5-Bromometagenediindole B (1) also demonstrated moderately cytotoxic activity against MCF7, B16, CNE2, Bel7402, and HT1080 tumor cell lines in vitro. PMID- 27258290 TI - Topical Formulation Comprising Fatty Acid Extract from Cod Liver Oil: Development, Evaluation and Stability Studies. AB - The purpose of this study was to develop a pharmaceutical formulation containing fatty acid extract rich in free omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid for topical use. Although the health benefits of cod liver oil and other fish oils taken orally as a dietary supplement have been acknowledged and exploited, it is clear that their use can be extended further to cover their antibacterial properties. In vitro evaluation showed that 20% (v/v) fatty acid extract exhibits good activity against strains of the Gram-positive bacteria Staphylococcus aureus, Enterococcus faecalis, Streptoccoccus pyogenes and Streptoccoccus pneumonia. Therefore, free polyunsaturated fatty acids from cod liver oil or other fish oils can be used as safe and natural antibacterial agents. In this study, ointment compositions containing free fatty acids as active antibacterial agents were prepared by using various natural waxes and characterized. The effects of different waxes, such as carnauba wax, ozokerite wax, laurel wax, beeswax, rice bran wax, candelilla wax and microcrystalline wax, in the concentration range of 1% to 5% (w/w) on the ointment texture, consistency and stability were evaluated. The results showed significant variations in texture, sensory and rheological profiles. This was attributed to the wax's nature and chain composition. Microcrystalline wax gave the best results but laurel wax, beeswax and rice bran wax exhibited excellent texturing, similar sensory profiles and well-balanced rheological properties. PMID- 27258291 TI - Review of the Literature on Determinants of Chemical Hazard Information Recall among Workers and Consumers. AB - In many low and middle income countries (LMIC), workers' and consumers' only access to risk and hazard information in relation to the chemicals they use or work with is on the chemical label and safety data sheet. Recall of chemical hazard information is vital in order for label warnings and precautionary information to promote effective safety behaviors. A literature review, therefore, was conducted on determinants of chemical hazard information recall among workers and consumers globally. Since comprehension and recall are closely linked, the determinants of both were reviewed. Literature was reviewed from both online and print peer reviewed journals for all study designs and countries. This review indicated that the level of education, previous training and the inclusion of pictograms on the hazard communication material are all factors that contribute to the recall of hazard information. The influence of gender and age on recall is incongruent and remains to be explored. More research is required on the demographic predictors of the recall of hazard information, the effect of design and non-design factors on recall, the effect of training on the recall among low literate populations and the examining of different regions or contexts. PMID- 27258292 TI - Increase in Suicide Rates by Hanging in the Population of Tabasco, Mexico between 2003 and 2012. AB - BACKGROUND: Worldwide, the suicide rate is decreasing. To examine changes in the rates of completed suicide in the Mexican population from 2003 to 2012, we analyzed these changes according to: (i) the method of suicide; (ii) age group and (iii) gender. METHODS: The data analyzed were obtained from governmental organizations from the State of Tabasco, Mexico. The data provided 1836 cases of subjects born and residing in Tabasco, who completed suicide in this state. RESULTS: Suicide by hanging was a common choice of suicide method for Mexicans. The rate of suicide by hanging increased from 5.80 to 6.49 per 100,000 persons between 2003 and 2012, a rate percentage increase of 11.89%. CONCLUSIONS: Hanging was found to be the most common choice of suicide in the Mexican population, probably because the materials required are easily available and the method does not require complicated techniques, especially in the 55-64 age group. Strategies for prevention and intervention should be developed for the Mexican population considering suicide rates by age group and gender. PMID- 27258293 TI - An Improved Multi-Objective Programming with Augmented epsilon-Constraint Method for Hazardous Waste Location-Routing Problems. AB - Hazardous waste location-routing problems are of importance due to the potential risk for nearby residents and the environment. In this paper, an improved mathematical formulation is developed based upon a multi-objective mixed integer programming approach. The model aims at assisting decision makers in selecting locations for different facilities including treatment plants, recycling plants and disposal sites, providing appropriate technologies for hazardous waste treatment, and routing transportation. In the model, two critical factors are taken into account: system operating costs and risk imposed on local residents, and a compensation factor is introduced to the risk objective function in order to account for the fact that the risk level imposed by one type of hazardous waste or treatment technology may significantly vary from that of other types. Besides, the policy instruments for promoting waste recycling are considered, and their influence on the costs and risk of hazardous waste management is also discussed. The model is coded and calculated in Lingo optimization solver, and the augmented epsilon-constraint method is employed to generate the Pareto optimal curve of the multi-objective optimization problem. The trade-off between different objectives is illustrated in the numerical experiment. PMID- 27258294 TI - Tracking Restoration of Park and Urban Street Settings in Coronary Artery Disease Patients. AB - The physiological effects of natural and urban environments on the cardiovascular system of coronary artery disease (CAD) patients are not fully understood. This controlled field study examines the effects of restorative walking in a park vs. in an urban street environment on CAD patients' stress parameters and cardiac function. METHODS: Twenty stable CAD patients were randomly allocated to 7 days controlled walking in a city park or in an urban street environment group. The relationship between different environmental exposures and health effects was analyzed using Wilcoxon signed-rank test and exact Mann-Whitney U test. RESULTS: The mean reduction in cortisol levels and negative effects after the walk on the first day was greater in the city park than in the urban street exposed group, while a reduction in negative effects in the urban group were greater after seven days. The reduction in diastolic blood pressure (DBP) in the park group was evident on the seventh day before the walk (-4 mm Hg, p = 0.031) and 60 min after the walk (-6.00 mm Hg, p = 0.002). The cortisol slope was negatively associated with the DBP changes (r = -0.514, p < 0.05). CONCLUSIONS: Physical activity in a green environment with noise and air pollution levels lower than in an urban environment has a greater positive effect on CAD patients' stress level and hemodynamic parameters. Mitigating green environmental influences may allow urban residents to maintain health and reduce disability. PMID- 27258295 TI - Children's Personal Exposure Measurements to Extremely Low Frequency Magnetic Fields in Italy. AB - Extremely low frequency magnetic fields (ELF-MFs) exposure is still a topic of concern due to their possible impact on children's health. Although epidemiological studies claimed an evidence of a possible association between ELF MF above 0.4 MUT and childhood leukemia, biological mechanisms able to support a causal relationship between ELF-MF and this disease were not found yet. To provide further knowledge about children's ELF-MF exposure correlated to children's daily activities, a measurement study was conducted in Milan (Italy). Eighty-six children were recruited, 52 of whom were specifically chosen with respect to the distance to power lines and built-in transformers to oversample potentially highly exposed children. Personal and bedroom measurements were performed for each child in two different seasons. The major outcomes of this study are: (1) median values over 24-h personal and bedroom measurements were <3 MUT established by the Italian law as the quality target; (2) geometric mean values over 24-h bedroom measurements were mostly <0.4 MUT; (3) seasonal variations did not significantly influence personal and bedroom measurements; (4) the highest average MF levels were mostly found at home during the day and outdoors; (5) no significant differences were found in the median and geometric mean values between personal and bedroom measurements, but were found in the arithmetic mean. PMID- 27258297 TI - LBMR: Load-Balanced Multipath Routing for Wireless Data-Intensive Transmission in Real-Time Medical Monitoring. AB - In wireless networks, low-power Zigbee is an excellent network solution for wireless medical monitoring systems. Medical monitoring generally involves transmission of a large amount of data and easily causes bottleneck problems. Although Zigbee's AODV mesh routing provides extensible multi-hop data transmission to extend network coverage, it originally does not, and needs to support some form of load balancing mechanism to avoid bottlenecks. To guarantee a more reliable multi-hop data transmission for life-critical medical applications, we have developed a multipath solution, called Load-Balanced Multipath Routing (LBMR) to replace Zigbee's routing mechanism. LBMR consists of three main parts: Layer Routing Construction (LRC), a Load Estimation Algorithm (LEA), and a Route Maintenance (RM) mechanism. LRC assigns nodes into different layers based on the node's distance to the medical data gateway. Nodes can have multiple next-hops delivering medical data toward the gateway. All neighboring layer-nodes exchange flow information containing current load, which is the used by the LEA to estimate future load of next-hops to the gateway. With LBMR, nodes can choose the neighbors with the least load as the next-hops and thus can achieve load balancing and avoid bottlenecks. Furthermore, RM can detect route failures in real-time and perform route redirection to ensure routing robustness. Since LRC and LEA prevent bottlenecks while RM ensures routing fault tolerance, LBMR provides a highly reliable routing service for medical monitoring. To evaluate these accomplishments, we compare LBMR with Zigbee's AODV and another multipath protocol, AOMDV. The simulation results demonstrate LBMR achieves better load balancing, less unreachable nodes, and better packet delivery ratio than either AODV or AOMDV. PMID- 27258296 TI - A Comprehensive Evaluation of the Burden of Heat-Related Illness and Death within the Florida Population. AB - The failure of the human body to thermoregulate can lead to severe outcomes (e.g., death) and lasting physiological damage. However, heat-related illness (HRI) is highly preventable via individual- and community-level modification. A thorough understanding of the burden is necessary for effective intervention. This paper describes the burden of severe HRI morbidity and mortality among residents of a humid subtropical climate. Work-related and non-work-related HRI emergency department (ED) visits, hospitalizations, and deaths among Florida residents during May to October (2005-2012) were examined. Sub-groups susceptible to HRI were identified. The age-adjusted rates/100,000 person-years for non-work related HRI were 33.1 ED visits, 5.9 hospitalizations, and 0.2 deaths, while for work-related HRI/100,000 worker-years there were 8.5 ED visits, 1.1 hospitalizations, and 0.1 deaths. The rates of HRI varied by county, data source, and work-related status, with the highest rates observed in the panhandle and south central Florida. The sub-groups with the highest relative rates regardless of data source or work-relatedness were males, minorities, and rural residents. Those aged 15-35 years had the highest ED visit rates, while for non-work-related hospitalizations and deaths the rates increased with age. The results of this study can be used for targeted interventions and evaluating changes in the HRI burden over time. PMID- 27258298 TI - Cloning the Horse RNA Polymerase I Promoter and Its Application to Studying Influenza Virus Polymerase Activity. AB - An influenza virus polymerase reconstitution assay based on the human, dog, or chicken RNA polymerase I (PolI) promoter has been developed and widely used to study the polymerase activity of the influenza virus in corresponding cell types. Although it is an important member of the influenza virus family and has been known for sixty years, no studies have been performed to clone the horse PolI promoter or to study the polymerase activity of equine influenza virus (EIV) in horse cells. In our study, the horse RNA PolI promoter was cloned from fetal equine lung cells. Using the luciferase assay, it was found that a 500 bp horse RNA PolI promoter sequence was required for efficient transcription. Then, using the developed polymerase reconstitution assay based on the horse RNA PolI promoter, the polymerase activity of two EIV strains was compared, and equine myxovirus resistance A protein was identified as having the inhibiting EIV polymerase activity function in horse cells. Our study enriches our knowledge of the RNA PolI promoter of eukaryotic species and provides a useful tool for the study of influenza virus polymerase activity in horse cells. PMID- 27258300 TI - Protein Supplementation Does Not Further Increase Latissimus Dorsi Muscle Fiber Hypertrophy after Eight Weeks of Resistance Training in Novice Subjects, but Partially Counteracts the Fast-to-Slow Muscle Fiber Transition. AB - The response to resistance training and protein supplementation in the latissimus dorsi muscle (LDM) has never been investigated. We investigated the effects of resistance training (RT) and protein supplementation on muscle mass, strength, and fiber characteristics of the LDM. Eighteen healthy young subjects were randomly assigned to a progressive eight-week RT program with a normal protein diet (NP) or high protein diet (HP) (NP 0.85 vs. HP 1.8 g of protein.kg(-1).day( 1)). One repetition maximum tests, magnetic resonance imaging for cross-sectional muscle area (CSA), body composition, and single muscle fibers mechanical and phenotype characteristics were measured. RT induced a significant gain in strength (+17%, p < 0.0001), whole muscle CSA (p = 0.024), and single muscle fibers CSA (p < 0.05) of LDM in all subjects. Fiber isometric force increased in proportion to CSA (+22%, p < 0.005) and thus no change in specific tension occurred. A significant transition from 2X to 2A myosin expression was induced by training. The protein supplementation showed no significant effects on all measured outcomes except for a smaller reduction of 2X myosin expression. Our results suggest that in LDM protein supplementation does not further enhance RT induced muscle fiber hypertrophy nor influence mechanic muscle fiber characteristics but partially counteracts the fast-to-slow fiber shift. PMID- 27258301 TI - Protein-Pacing and Multi-Component Exercise Training Improves Physical Performance Outcomes in Exercise-Trained Women: The PRISE 3 Study. AB - The beneficial cardiometabolic and body composition effects of combined protein pacing (P; 5-6 meals/day at 2.0 g/kg BW/day) and multi-mode exercise (resistance, interval, stretching, endurance; RISE) training (PRISE) in obese adults has previously been established. The current study examines PRISE on physical performance (endurance, strength and power) outcomes in healthy, physically active women. Thirty exercise-trained women (>4 days exercise/week) were randomized to either PRISE (n = 15) or a control (CON, 5-6 meals/day at 1.0 g/kg BW/day; n = 15) for 12 weeks. Muscular strength (1-RM bench press, 1-RM BP) endurance (sit-ups, SUs; push-ups, PUs), power (bench throws, BTs), blood pressure (BP), augmentation index, (AIx), and abdominal fat mass were assessed at Weeks 0 (pre) and 13 (post). At baseline, no differences existed between groups. Following the 12-week intervention, PRISE had greater gains (p < 0.05) in SUs, PUs (6 +/- 7 vs. 10 +/- 7, 40%; 8 +/- 13 vs. 14 +/- 12, 43% ?reps, respectively), BTs (11 +/- 35 vs. 44 +/- 34, 75% ?watts), AIx (1 +/- 9 vs. -5 +/- 11, 120%), and DBP (-5 +/- 9 vs. -11 +/- 11, 55% ?mmHg). These findings suggest that combined protein-pacing (P; 5-6 meals/day at 2.0 g/kg BW/day) diet and multi-component exercise (RISE) training (PRISE) enhances muscular endurance, strength, power, and cardiovascular health in exercise-trained, active women. PMID- 27258299 TI - Insulin-Sensitizing Effects of Omega-3 Fatty Acids: Lost in Translation? AB - Omega-3 polyunsaturated fatty acids (n-3 PUFA) of marine origin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been long studied for their therapeutic potential in the context of type 2 diabetes, insulin resistance, and glucose homeostasis. Glaring discordance between observations in animal and human studies precludes, to date, any practical application of n-3 PUFA as nutritional therapeutics against insulin resistance in humans. Our objective in this review is to summarize current knowledge and provide an up-to-date commentary on the therapeutic value of EPA and DHA supplementation for improving insulin sensitivity in humans. We also sought to discuss potential mechanisms of n-3 PUFA action in target tissues, in specific skeletal muscle, based on our recent work, as well as in liver and adipose tissue. We conducted a literature search to include all preclinical and clinical studies performed within the last two years and to comment on representative studies published earlier. Recent studies support a growing consensus that there are beneficial effects of n-3 PUFA on insulin sensitivity in rodents. Observational studies in humans are encouraging, however, the vast majority of human intervention studies fail to demonstrate the benefit of n-3 PUFA in type 2 diabetes or insulin-resistant non-diabetic people. Nevertheless, there are still several unanswered questions regarding the potential impact of n-3 PUFA on metabolic function in humans. PMID- 27258302 TI - Age-Dependent Changes in Resting Energy Expenditure (REE): Insights from Detailed Body Composition Analysis in Normal and Overweight Healthy Caucasians. AB - Age-related changes in organ and tissue masses may add to changes in the relationship between resting energy expenditure (REE) and fat free mass (FFM) in normal and overweight healthy Caucasians. Secondary analysis using cross sectional data of 714 healthy normal and overweight Caucasian subjects (age 18-83 years) with comprehensive information on FFM, organ and tissue masses (as assessed by magnetic resonance imaging (MRI)), body density (as assessed by Air Displacement Plethysmography (ADP)) and hydration (as assessed by deuterium dilution (D2O)) and REE (as assessed by indirect calorimetry). High metabolic rate organs (HMR) summarized brain, heart, liver and kidney masses. Ratios of HMR organs and muscle mass (MM) in relation to FFM were considered. REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. REE, FFM, specific metabolic rates, the REE-FFM relationship, HOMA, CRP, and thyroid hormone levels change with age. The age-related decrease in FFM explained 59.7% of decreases in REE. Mean residuals of the REE-FFM association were positive in young adults but became negative in older subjects. When compared to young adults, proportions of MM to FFM decreased with age, whereas contributions of liver and heart did not differ between age groups. HOMA, TSH and inflammation (plasma CRP-levels) explained 4.2%, 2.0% and 1.4% of the variance in the REE-FFM residuals, but age and plasma T3-levels had no effects. HMR to FFM and MM to FFM ratios together added 11.8% on to the variance of REE-FFM residuals. Differences between REE and REEc increased with age, suggesting age related changes in specific metabolic rates of organs and tissues. This bias was partly explained by plasmaT3-levels. Age-related changes in REE are explained by (i) decreases in fat free mass; (ii) a decrease in the contributions of organ and muscle masses to FFM; and (iii) decreases in specific organ and tissue metabolic rates. Age-dependent changes in the REE-FFMassociation are explained by composition of FFM, inflammation and thyroid hormones. PMID- 27258304 TI - Does Metabolically Healthy Obesity Exist? AB - The relationship between obesity and other metabolic diseases have been deeply studied. However, there are clinical inconsistencies, exceptions to the paradigm of "more fat means more metabolic disease", and the subjects in this condition are referred to as metabolically healthy obese (MHO).They have long-standing obesity and morbid obesity but can be considered healthy despite their high degree of obesity. We describe the variable definitions of MHO, the underlying mechanisms that can explain the existence of this phenotype caused by greater adipose tissue inflammation or the different capacity for adipose tissue expansion and functionality apart from other unknown mechanisms. We analyze whether these subjects improve after an intervention (traditional lifestyle recommendations or bariatric surgery) or if they stay healthy as the years pass. MHO is common among the obese population and constitutes a unique subset of characteristics that reduce metabolic and cardiovascular risk factors despite the presence of excessive fat mass. The protective factors that grant a healthier profile to individuals with MHO are being elucidated. PMID- 27258305 TI - Does the Australasian "Health Star Rating" Front of Pack Nutritional Label System Work? AB - This article describes an experiment to measure the impact of the Australasian "Health Star Rating" front of pack nutritional label system on consumer choice behaviour. This system presents a one-half to five star rating of nutritional quality via the front facings of food product packages. While this system has been recently rolled out across Australasia, no test of its impact on food choice has been conducted. A sample of 1200 consumers was recruited on exit from supermarkets in New Zealand. A 2 * 2 factorial design was used with two levels of cold cereal product nutritional status (high, five star/low, two star) and two levels of the Health Star Rating label (present/absent). The dependent variable was revealed choice behaviour. The results indicated that the presence of the label had a significant depressive effect on consumer preference, but that this impact was not moderated in any way by the nutritional status expressed by the label. The result represents a significant functional failure of the Health Star Rating label in this research environment. The nature of the failure is consistent with the consumers processing the label in much the same way as the nominal brand cues that dominate the retail food packaging. PMID- 27258303 TI - Crucial Role of Vitamin D in the Musculoskeletal System. AB - Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D's central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported. PMID- 27258306 TI - The Relationship between Vitamin D Status and Allergic Diseases in New Zealand Preschool Children. AB - Recent research on vitamin D in young children has expanded from bone development to exploring immunomodulatory effects. Our aim was to investigate the relationship of vitamin D status and allergic diseases in preschool-aged children in New Zealand. Dried capillary blood spots were collected from 1329 children during late-winter to early-spring for 25(OH)D measurement by LC-MS/MS. Caregivers completed a questionnaire about their child's recent medical history. Analysis was by multivariable logistic regression. Mean 25(OH)D concentration was 52(SD19) nmol/L, with 7% of children <25 nmol/L and 49% <50 nmol/L. Children with 25(OH)D concentrations >=75 nmol/L (n = 29) had a two-fold increased risk for parent-report of doctor-diagnosed food allergy compared to children with 25(OH)D 50-74.9 nmol/L (OR = 2.21, 1.33-3.68, p = 0.002). No associations were present between 25(OH)D concentration and presence of parent-reported eczema, allergic rhinoconjunctivitis or atopic asthma. Vitamin D deficiency was not associated with several allergic diseases in these New Zealand preschool children. In contrast, high 25(OH)D concentrations were associated with a two-fold increased risk of parental-report food allergy. This increase supports further research into the association between vitamin D status and allergic disease in preschool children. PMID- 27258307 TI - Salvianolic Acid B Inhibits Abeta Generation by Modulating BACE1 Activity in SH SY5Y-APPsw Cells. AB - Alzheimer's disease (AD) is a neurodegenerative disease in humans. The accumulation of amyloid-beta (Abeta) plays a critical role in the pathogenesis of AD. Previous studies indicated that Salvianolic acid B (SalB) could ameliorate Abeta-induced memory impairment. However, whether SalB could influence the generation of Abeta is unclear. Here, we show that SalB (25, 50, or 100 uM) reduces the generation of Abeta40 and Abeta42 in culture media by decreasing the protein expressions of BACE1 and sAPPbeta in SH-SY5Y-APPsw cells. Meanwhile, SalB increases the levels of ADAM10 and sAPPalpha in the cells. However, SalB has no impact on the protein expressions of APP and PS1. Moreover, SalB attenuates oxidative stress and inhibits the activity of GSK3beta, which might be related to the suppression of BACE1 expression and amyloidogenesis. Our study suggests that SalB is a promising therapeutic agent for AD by targeting Abeta generation. PMID- 27258309 TI - Comments on "Mycobiota and Mycotoxins in Traditional Medicinal Seeds from China. Toxins 2015, 7, 3858-3875"- in Attributing Ochratoxin A Biosynthesis Within the Genus Penicillium Occurring on Natural Agricultural Produce. AB - The unusual attribution of trace amounts of ochratoxin A in some Chinese food commodities to Penicillium polonicum is questioned by European experience in searches for ochratoxinogenic food-spoilage Penicillia, where mistaken attribution is now known to have been due to cryptic Penicillium verrucosum contamination. Consequently, selection of single-spore isolates is recommended as pre-requisite for attributing mycotoxin biosynthetic potential to fungi. PMID- 27258310 TI - Response to Peter Mantle. Comments on "Mycobiota and Mycotoxins in Traditional Medicinal Seeds from China. Toxins 2015, 7, 3858-3875"-Rigour in Attributing Ochratoxin A Biosynthesis within the Genus Penicillium Occurring on Natural Agricultural Produce. AB - My colleagues and I appreciate the comments and constructive suggestions on our manuscript "Mycobiota and Mycotoxins in Traditional Medicinal Seeds from China".[...]. PMID- 27258308 TI - Nutrition in Pediatric Inflammatory Bowel Disease: From Etiology to Treatment. A Systematic Review. AB - Nutrition is involved in several aspects of pediatric inflammatory bowel disease (IBD), ranging from disease etiology to induction and maintenance of disease. With regards to etiology, there are pediatric data, mainly from case-control studies, which suggest that some dietary habits (for example consumption of animal protein, fatty foods, high sugar intake) may predispose patients to IBD onset. As for disease treatment, exclusive enteral nutrition (EEN) is an extensively studied, well established, and valid approach to the remission of pediatric Crohn's disease (CD). Apart from EEN, several new nutritional approaches are emerging and have proved to be successful (specific carbohydrate diet and CD exclusion diet) but the available evidence is not strong enough to recommend this kind of intervention in clinical practice and new large experimental controlled studies are needed, especially in the pediatric population. Moreover, efforts are being made to identify foods with anti inflammatory properties such as curcumin and long-chain polyunsaturated fatty acids n-3, which can possibly be effective in maintenance of disease. The present systematic review aims at reviewing the scientific literature on all aspects of nutrition in pediatric IBD, including the most recent advances on nutritional therapy. PMID- 27258311 TI - Sequence Variability in Staphylococcal Enterotoxin Genes seb, sec, and sed. AB - Ingestion of staphylococcal enterotoxins preformed by Staphylococcus aureus in food leads to staphylococcal food poisoning, the most prevalent foodborne intoxication worldwide. There are five major staphylococcal enterotoxins: SEA, SEB, SEC, SED, and SEE. While variants of these toxins have been described and were linked to specific hosts or levels or enterotoxin production, data on sequence variation is still limited. In this study, we aim to extend the knowledge on promoter and gene variants of the major enterotoxins SEB, SEC, and SED. To this end, we determined seb, sec, and sed promoter and gene sequences of a well-characterized set of enterotoxigenic Staphylococcus aureus strains originating from foodborne outbreaks, human infections, human nasal colonization, rabbits, and cattle. New nucleotide sequence variants were detected for all three enterotoxins and a novel amino acid sequence variant of SED was detected in a strain associated with human nasal colonization. While the seb promoter and gene sequences exhibited a high degree of variability, the sec and sed promoter and gene were more conserved. Interestingly, a truncated variant of sed was detected in all tested sed harboring rabbit strains. The generated data represents a further step towards improved understanding of strain-specific differences in enterotoxin expression and host-specific variation in enterotoxin sequences. PMID- 27258312 TI - Molecular Characterization of Three Novel Phospholipase A2 Proteins from the Venom of Atheris chlorechis, Atheris nitschei and Atheris squamigera. AB - Secretory phospholipase A2 (sPLA2) is known as a major component of snake venoms and displays higher-order catalytic hydrolysis functions as well as a wide range of pathological effects. Atheris is not a notoriously dangerous genus of snakes although there are some reports of fatal cases after envenomation due to the effects of coagulation disturbances and hemorrhaging. Molecular characterization of Atheris venom enzymes is incomplete and there are only a few reports in the literature. Here, we report, for the first time, the cloning and characterization of three novel cDNAs encoding phospholipase A2 precursors (one each) from the venoms of the Western bush viper (Atheris chlorechis), the Great Lakes bush viper (Atheris nitschei) and the Variable bush viper (Atheris squamigera), using a "shotgun cloning" strategy. Open-reading frames of respective cloned cDNAs contained putative 16 residue signal peptides and mature proteins composed of 121 to 123 amino acid residues. Alignment of mature protein sequences revealed high degrees of structural conservation and identity with Group II venom PLA2 proteins from other taxa within the Viperidae. Reverse-phase High Performance Liquid Chromatography (HPLC) profiles of these three snake venoms were obtained separately and chromatographic fractions were assessed for phospholipase activity using an egg yolk suspension assay. The molecular masses of mature proteins were all identified as approximately 14 kDa. Mass spectrometric analyses of the fractionated oligopeptides arising from tryptic digestion of intact venom proteins, was performed for further structural characterization. PMID- 27258314 TI - Berry Leaves: An Alternative Source of Bioactive Natural Products of Nutritional and Medicinal Value. AB - Berry fruits are recognized, worldwide, as "superfoods" due to the high content of bioactive natural products and the health benefits deriving from their consumption. Berry leaves are byproducts of berry cultivation; their traditional therapeutic use against several diseases, such as the common cold, inflammation, diabetes, and ocular dysfunction, has been almost forgotten nowadays. Nevertheless, the scientific interest regarding the leaf composition and beneficial properties grows, documenting that berry leaves may be considered an alternative source of bioactives. The main bioactive compounds in berry leaves are similar as in berry fruits, i.e., phenolic acids and esters, flavonols, anthocyanins, and procyanidins. The leaves are one of the richest sources of chlorogenic acid. In various studies, these secondary metabolites have demonstrated antioxidant, anti-inflammatory, cardioprotective, and neuroprotective properties. This review focuses on the phytochemical composition of the leaves of the commonest berry species, i.e., blackcurrant, blackberry, raspberry, bilberry, blueberry, cranberry, and lingonberry leaves, and presents their traditional medicinal uses and their biological activities in vitro and in vivo. PMID- 27258313 TI - The Hagfish Gland Thread Cell: A Fiber-Producing Cell Involved in Predator Defense. AB - Fibers are ubiquitous in biology, and include tensile materials produced by specialized glands (such as silks), extracellular fibrils that reinforce exoskeletons and connective tissues (such as chitin and collagen), as well as intracellular filaments that make up the metazoan cytoskeleton (such as F-actin, microtubules, and intermediate filaments). Hagfish gland thread cells are unique in that they produce a high aspect ratio fiber from cytoskeletal building blocks within the confines of their cytoplasm. These threads are elaborately coiled into structures that readily unravel when they are ejected into seawater from the slime glands. In this review we summarize what is currently known about the structure and function of gland thread cells and we speculate about the mechanism that these cells use to produce a mechanically robust fiber that is almost one hundred thousand times longer than it is wide. We propose that a key feature of this mechanism involves the unidirectional rotation of the cell's nucleus, which would serve to twist disorganized filaments into a coherent thread and impart a torsional stress on the thread that would both facilitate coiling and drive energetic unravelling in seawater. PMID- 27258315 TI - Aeromonas hydrophila OmpW PLGA Nanoparticle Oral Vaccine Shows a Dose-Dependent Protective Immunity in Rohu (Labeo rohita). AB - Aeromonas hydrophila is a Gram-negative bacterium that causes high mortality in different fish species and at different growth stages. Although vaccination has significantly contributed to the decline of disease outbreaks in aquaculture, the use of oral vaccines has lagged behind the injectable vaccines due to lack of proven efficacy, that being from primary immunization or by use of boost protocols. In this study, the outer membrane protein W (OmpW) of A. hydrophila was cloned, purified, and encapsulated in poly d,l-lactide-co-glycolic acid (PLGA) nanoparticles (NPs) for oral vaccination of rohu (Labeo rohita Hamilton). The physical properties of PLGA NPs encapsulating the recombinant OmpW (rOmpW) was characterized as having a diameter of 370-375 nm, encapsulation efficiency of 53% and -19.3 mV zeta potential. In vitro release of rOmpW was estimated at 34% within 48 h of incubation in phosphate-buffered saline. To evaluate the efficacy of the NP-rOmpW oral vaccine, two antigen doses were orally administered in rohu with a high antigen (HiAg) dose that had twice the amount of antigens compared to the low antigen (LoAg) dose. Antibody levels obtained after vaccination showed an antigen dose dependency in which fish from the HiAg group had higher antibody levels than those from the LoAg group. The antibody levels corresponded with post challenge survival proportions (PCSPs) and relative percent survival (RPS) in which the HiAg group had a higher PCSP and RPS than the LoAg group. Likewise, the ability to inhibit A. hydrophila growth on trypticase soy agar (TSA) by sera obtained from the HiAg group was higher than that from the LoAg group. Overall, data presented here shows that OmpW orally administered using PLGA NPs is protective against A. hydrophila infection with the level of protective immunity induced by oral vaccination being antigen dose-dependent. Future studies should seek to optimize the antigen dose and duration of oral immunization in rohu in order to induce the highest protection in vaccinated fish. PMID- 27258317 TI - Insights into the Stress Response Triggered by Kasugamycin in Escherichia coli. AB - The bacteriostatic aminoglycoside antibiotic kasugamycin inhibits protein synthesis at an initial step without affecting translation elongation. It binds to the mRNA track of the ribosome and prevents formation of the translation initiation complex on canonical mRNAs. In contrast, translation of leaderless mRNAs continues in the presence of the drug in vivo. Previously, we have shown that kasugamycin treatment in E. coli stimulates the formation of protein depleted ribosomes that are selective for leaderless mRNAs. Here, we provide evidence that prolonged kasugamycin treatment leads to selective synthesis of specific proteins. Our studies indicate that leaderless and short-leadered mRNAs are generated by different molecular mechanisms including alternative transcription and RNA processing. Moreover, we provide evidence for ribosome heterogeneity in response to kasugamycin treatment by alteration of the modification status of the stalk proteins bL7/L12. PMID- 27258318 TI - Development of Database Assisted Structure Identification (DASI) Methods for Nontargeted Metabolomics. AB - Metabolite structure identification remains a significant challenge in nontargeted metabolomics research. One commonly used strategy relies on searching biochemical databases using exact mass. However, this approach fails when the database does not contain the unknown metabolite (i.e., for unknown-unknowns). For these cases, constrained structure generation with combinatorial structure generators provides a potential option. Here we evaluated structure generation constraints based on the specification of: (1) substructures required (i.e., seed structures); (2) substructures not allowed; and (3) filters to remove incorrect structures. Our approach (database assisted structure identification, DASI) used predictive models in MolFind to find candidate structures with chemical and physical properties similar to the unknown. These candidates were then used for seed structure generation using eight different structure generation algorithms. One algorithm was able to generate correct seed structures for 21/39 test compounds. Eleven of these seed structures were large enough to constrain the combinatorial structure generator to fewer than 100,000 structures. In 35/39 cases, at least one algorithm was able to generate a correct seed structure. The DASI method has several limitations and will require further experimental validation and optimization. At present, it seems most useful for identifying the structure of unknown-unknowns with molecular weights <200 Da. PMID- 27258316 TI - Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems. AB - Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID- 27258319 TI - Reconfiguration of N Metabolism upon Hypoxia Stress and Recovery: Roles of Alanine Aminotransferase (AlaAT) and Glutamate Dehydrogenase (GDH). AB - In the context of climatic change, more heavy precipitation and more frequent flooding and waterlogging events threaten the productivity of arable farmland. Furthermore, crops were not selected to cope with flooding- and waterlogging induced oxygen limitation. In general, low oxygen stress, unlike other abiotic stresses (e.g., cold, high temperature, drought and saline stress), received little interest from the scientific community and less financial support from stakeholders. Accordingly, breeding programs should be developed and agronomical practices should be adapted in order to save plants' growth and yield-even under conditions of low oxygen availability (e.g., submergence and waterlogging). The prerequisite to the success of such breeding programs and changes in agronomical practices is a good knowledge of how plants adapt to low oxygen stress at the cellular and the whole plant level. In the present paper, we summarized the recent knowledge on metabolic adjustment in general under low oxygen stress and highlighted thereafter the major changes pertaining to the reconfiguration of amino acids syntheses. We propose a model showing (i) how pyruvate derived from active glycolysis upon hypoxia is competitively used by the alanine aminotransferase/glutamate synthase cycle, leading to alanine accumulation and NAD+ regeneration. Carbon is then saved in a nitrogen store instead of being lost through ethanol fermentative pathway. (ii) During the post-hypoxia recovery period, the alanine aminotransferase/glutamate dehydrogenase cycle mobilizes this carbon from alanine store. Pyruvate produced by the reverse reaction of alanine aminotransferase is funneled to the TCA cycle, while deaminating glutamate dehydrogenase regenerates, reducing equivalent (NADH) and 2-oxoglutarate to maintain the cycle function. PMID- 27258320 TI - Efficient Virus-Induced Gene Silencing in Solanum rostratum. AB - Solanum rostratum is a "super weed" that grows fast, is widespread, and produces the toxin solanine, which is harmful to both humans and other animals. To our knowledge, no study has focused on its molecular biology owing to the lack of available transgenic methods and sequence information for S. rostratum. Virus induced gene silencing (VIGS) is a powerful tool for the study of gene function in plants; therefore, in the present study, we aimed to establish tobacco rattle virus (TRV)-derived VIGS in S. rostratum. The genes for phytoene desaturase (PDS) and Chlorophyll H subunit (ChlH) of magnesium protoporphyrin chelatase were cloned from S. rostratum and used as reporters of gene silencing. It was shown that high-efficiency VIGS can be achieved in the leaves, flowers, and fruit of S. rostratum. Moreover, based on our comparison of three different types of infection methods, true leaf infection was found to be more efficient than cotyledon and sprout infiltration in long-term VIGS in multiple plant organs. In conclusion, the VIGS technology and tomato genomic sequences can be used in the future to study gene function in S. rostratum. PMID- 27258321 TI - Protection of the photosynthetic apparatus against dehydration stress in the resurrection plant Craterostigma pumilum. AB - The group of homoiochlorophyllous resurrection plants evolved the unique capability to survive severe drought stress without dismantling the photosynthetic machinery. This implies that they developed efficient strategies to protect the leaves from reactive oxygen species (ROS) generated by photosynthetic side reactions. These strategies, however, are poorly understood. Here, we performed a detailed study of the photosynthetic machinery in the homoiochlorophyllous resurrection plant Craterostigma pumilum during dehydration and upon recovery from desiccation. During dehydration and rehydration, C. pumilum deactivates and activates partial components of the photosynthetic machinery in a specific order, allowing for coordinated shutdown and subsequent reinstatement of photosynthesis. Early responses to dehydration are the closure of stomata and activation of electron transfer to oxygen accompanied by inactivation of the cytochrome b6 f complex leading to attenuation of the photosynthetic linear electron flux (LEF). The decline in LEF is paralleled by a gradual increase in cyclic electron transport to maintain ATP production. At low water contents, inactivation and supramolecular reorganization of photosystem II becomes apparent, accompanied by functional detachment of light-harvesting complexes and interrupted access to plastoquinone. This well-ordered sequence of alterations in the photosynthetic thylakoid membranes helps prepare the plant for the desiccated state and minimize ROS production. PMID- 27258322 TI - The Fellow and the Professor Revisited. PMID- 27258323 TI - Brief Report: Mediation Analysis with an Ordinal Outcome. AB - The article presents concepts and methods for mediation analysis for an ordinal outcome. We give definitions of natural direct and indirect effects using counterfactuals for ordinal outcomes; in this context, there are potentially different effects for any two levels of the outcome, and we consider difference and ratio scales. The confounding assumptions required for identification are similar to that in the existing mediation analysis literature. We discuss different modeling strategies for estimation. Under a proportional odds model with a reference category that is common, the direct and indirect effects on a ratio scale can each be summarized by a single estimate and are available in closed form; otherwise the effects may differ across categories compared and can be obtained by numeric simulation methods. PMID- 27258324 TI - In Utero Exposure to Aspirin and Risk of Asthma in Childhood. AB - BACKGROUND: Aspirin is widely used in general population and low-dose aspirin is commonly prescribed to prevent recurrent pregnancy loss associated with antiphospholipid syndrome and preeclampsia, often used throughout pregnancy. But aspirin is associated with asthma pathogenesis. We aim to examine whether in utero exposure to aspirin at different fetal stages is associated with asthma in childhood. METHODS: We used data from the Collaborative Perinatal Project. Maternal exposure to aspirin before and during pregnancy was recorded at each prenatal visit. Children were followed up to 7 years of age. A total of 19,928 singleton children without maternal history of asthma were included. We used multilevel multiple logistic regression models to control for potential confounders. RESULTS: In utero exposure to aspirin was associated with an increased risk of childhood asthma (adjusted odds ratio [aORs] = 1.3, 95% confidence interval [CI] = 1.1, 1.6). aORs for exposure in first, second, and third trimesters were 1.1 (95% CI = 0.87, 1.3), 1.2 (95% CI = 1.0, 1.4), and 1.4 (95% CI = 1.1, 1.6), respectively. Furthermore, aORs of asthma were 1.3 (95% CI = 1.0, 1.7) and 1.3 (95% CI = 1.0, 1.7) for aspirin use for 2 to 7 days or more than 7 days in third trimester, respectively. CONCLUSION: In utero exposure to therapeutic dose of aspirin even just briefly in late pregnancy is associated with childhood asthma by 7 years of age. More research is needed to carefully examine the association between low-dose aspirin with extended exposure period and long-term child outcomes. PMID- 27258325 TI - Short-term Exposure to Ozone and Mortality in Subjects With and Without Previous Cardiovascular Disease. AB - BACKGROUND: Exposure to ground level ozone (O3) is a public health problem associated with a range of risks across population subgroups. Our aim was to investigate the role of previous cardiovascular diseases (CVDs) in mortality related to short-term O3 exposure. METHODS: Deaths between 1990 and 2010 in Stockholm County were matched with previous hospitalizations in Swedish registries. An urban background monitoring station provided hourly values of air quality data, from which we calculated 8-hour running averages and daily 8-hour maximum. We analyzed associations between daily O3 concentrations and mortality among persons with and without previous CVD hospitalization with a generalized additive model adjusted for time trend, influenza, and weather. We also performed two-pollutant models. RESULTS: There were 302,283 nontrauma-related deaths, out of which 196,916 had previous CVD hospitalization. The mean concentration of daily maximum 8-hour O3 was 62.9 MUg/m. An average 10 MUg/m increase in the same and preceding day was associated with an increased mortality of 1.72% (95% confidence interval: 0.44%, 3.02%) in those with prior admission for acute myocardial infarction (AMI), which was more than three times higher than for those with no previous AMI (0.50, 95% confidence interval: 0.10%, 0.89%, P value for interaction 0.098). The association between O3 and mortality remained essentially unchanged in two-pollutant models with NO2, NOx, and PM10. CONCLUSIONS: Our study indicates that short-term exposure to O3 is associated with increased mortality in those with a previous hospitalization for AMI. PMID- 27258326 TI - Enhanced retention of bacteria by TiO2 nanoparticles in saturated porous media. AB - The simultaneous transport of TiO2 nanoparticles and bacteria Pseudomonas aeruginosa in saturated porous media was investigated. Nanoparticle and bacterium size and surface charge were measured as a function of electrolyte concentration. Sand column breakthrough curves were obtained for single and combined suspensions, at four different ionic strengths. DLVO and classical filtration theories were employed to model the interactions between particles and between particles and sand grains. Attachment of TiO2 to the sand was explained by electrostatic forces and these nanoparticles acted as bonds between the bacteria and the sand, leading to retention. Presence of TiO2 significantly increased the retention of bacteria in the sand bed, but microorganisms were released when nanomaterial influx ceased. The inclusion of nanomaterials in saturated porous media may have implications for the design and operation of sand filters in water treatment. PMID- 27258327 TI - Biomedical practices from a patient perspective. Experiences of Polish female migrants in Barcelona, Berlin and London. AB - This paper focuses on the diversity in patients' experience of bio-medicine and contrasts it with the normative view characteristic of health professionals. Ethnographic fieldwork among Polish migrant women in London, Barcelona and Berlin included interviews about their experiences with local healthcare and health professionals. Themes drawn from the narratives are differences between the cities in terms of communication between patients and health professionals, respect for patients' choices and dignity, attitudes to pregnancy and birth (different levels of medicalization), and paediatric care. It is argued that patients continuously negotiate among their own views and expectations based on previous experiences and knowledge from personal communication; internet forums and publications; and the offer of medical services in the countries of their settlement. Patients experience pluralism of therapeutic traditions within and outside bio-medicine. In turn, representatives of bio-medicine are rarely aware of other medical practices and beliefs and this leads to various misunderstandings. By highlighting the pluralism of medical practices in European countries and the increasing mobility of patients, this case study has useful implications for medical anthropologists and health professionals in a broader Western context, such as raising sensitivity to different communication strategies and a diversity of curing traditions and expectations. PMID- 27258328 TI - UV-A Protection From Auto Glass, Cataracts, and the Ophthalmologist. PMID- 27258329 TI - Effect of UVC radiation on mouse fibroblasts deficient for FAS-associated protein with death domain. AB - PURPOSE: Ultraviolet (UV) radiation-induced apoptosis enabled us to study the mechanism of DNA damage and to investigate how cells avoid consequences of damaged DNA. Cells with extensive DNA damage activate extrinsic and intrinsic pathways of apoptosis. The extrinsic pathway is coupled to a FAS-associated protein with death domain (FADD), an adaptor protein molecule necessary for mediating apoptotic signals through the cell. MATERIALS AND METHODS: Viability and apoptosis of wild-type and FADD-deficient mouse embryonic fibroblasts were investigated 1, 3, 24 and 48 h after exposure to three doses (50, 75 and 300 J/m(2)) of UVC radiation. Morphological changes were observed using DNA binding dyes (Hoechst and propidium iodide) while biochemical changes were monitored using immunodetection of the poly (ADP-ribose) polymerase (PARP) protein cleavage and caspase-3 activity assay. RESULTS: Results showed that the difference in cell death response between wild-type and FADD-deficient cells depended on dose and incubation time after exposure to UVC radiation. FADD-deficient cells are more sensitive to UVC radiation. Even though FADD-deficient cells lack an adapter protein of apoptotic extrinsic pathway, higher doses of UVC triggered their apoptotic response, while wild-type cells die mainly due to necrosis. A different pattern of caspase 3 activity and PARP cleavage was observed 24 h after radiation between two cell lines confirming higher apoptotic response in FADD-deficient cells. CONCLUSIONS: Wild-type cells can execute apoptosis via both, the mitochondrial and the receptor-mediated pathway whereas FADD-deficient cells can only activate the intrinsic pathway. There is a difference in UVC radiation response between two cell lines indicating the role of FADD in the selection of cell death modality. PMID- 27258330 TI - Molecular design and genetic optimization of antimicrobial peptides containing unnatural amino acids against antibiotic-resistant bacterial infections. AB - Antimicrobial peptides (AMPs) have been the focus of intense research towards the finding of a viable alternative to current small-molecule antibiotics, owing to their commonly observed and naturally occurring resistance against pathogens. However, natural peptides have many problems such as low bioavailability and high allergenicity that largely limit the clinical applications of AMPs. In the present study, an integrative protocol that combined chemoinformatics modeling, molecular dynamics simulations, and in vitro susceptibility test was described to design AMPs containing unnatural amino acids (AMP-UAAs). To fulfill this, a large panel of synthetic AMPs with determined activity was collected and used to perform quantitative structure-activity relationship (QSAR) modeling. The obtained QSAR predictors were then employed to direct genetic algorithm (GA) based optimization of AMP-UAA population, to which a number of commercially available, structurally diverse unnatural amino acids were introduced during the optimization process. Subsequently, several designed AMP-UAAs were confirmed to have high antibacterial potency against two antibiotic-resistant strains, i.e. multidrug-resistant Pseudomonas aeruginosa (MDRPA) and methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentration (MIC) < 10 MUg/ml. Structural dynamics characterizations revealed that the most potent AMP UAA peptide is an amphipathic helix that can spontaneously embed into an artificial lipid bilayer and exhibits a strong destructuring tendency associated with the embedding process. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 746-756, 2016. PMID- 27258331 TI - IPr3 Si3 Cl5 (+) : A Highly Reactive Cation with Silanide Character. AB - The reaction of a metastable SiCl2 solution with the sterically less-demanding carbene N,N-diisopropylimidazo-2-ylidene (IPr) yields the salt [(IPr3 Si3 Cl5 )(+) ]Cl(-) (1-Cl), containing a silyl cation with a Si3 backbone. Salt 1 is highly reactive, but it can be used as a reagent in deuterated dichloromethane, whereby dehalogenation with Me3 SiOTf (OTf=O3 SCF3 ) gives the dicationic silyl halide [(IPr3 Si3 Cl4 )](2+) 2. Quantum chemical calculations show that the HOMO is localized at the negatively charged central silicon atom of 1 and 2, and thus although both compounds are cations they are better described as silanides, which was also corroborated by NMR investigations. PMID- 27258332 TI - Construction of a bioreporter by heterogeneously expressing a Vibrio natriegens recA::luxCDABE fusion in Escherichia coli, and genotoxicity assessments of petrochemical-contaminated groundwater in northern China. AB - Here, we constructed an Escherichia coli recA::luxCDABE bioreporter for genotoxicity assessments. The recA promoter was cloned from the marine bacterium Vibrio natriegens. This bioreporter showed a dose-response relationship following induction by mitomycin C, and other pollutants or environmental samples could be calculated as mitomycin C equivalents, which provided a way to quantitatively compare the genotoxicities of different environmental samples. This bioreporter was used to evaluate the genotoxicity under a wide range of external environmental conditions, like temperatures ranging from 15 degrees C to 42 degrees C, pH between 4.0 and 9.0, and salinity ranging from 0% to 3%. This successfully extended its application from the laboratory to the field, and allowed the bioreporter to assess the genotoxicity and bioavailability of genotoxins in various environmental media, including surface water, groundwater, seawater, and soil matrix. Expression of V. natriegens recA in E. coli indicated a LexA-like regulator in V. natriegens, and the putative SOS box of V. natriegens recA was similar to that of E. coli. The genotoxicities of groundwater samples from a petrochemical-contaminated site in northern China were evaluated by this bioreporter assay, and the genotoxic levels were in accordance with contamination levels obtained by chemical analyses. PMID- 27258353 TI - Meiofauna communities, nematode diversity and C degradation rates in seagrass (Posidonia oceanica L.) and unvegetated sediments invaded by the algae Caulerpa cylindracea (Sonder). AB - We investigated meiofauna and sedimentary C cycling in seagrass (Posidonia oceanica) and unvegetated sediments invaded and not invaded by the non-indigenous tropical algae Caulerpa cylindracea. In both habitats, invaded sediments were characterized by higher organic matter contents. No effect was observed for prokaryotes and C degradation rates. In seagrass sediments, C turnover in invaded beds was about half that in not invaded ones. Meiofaunal communities varied significantly among invaded and not invaded grounds only in bare sediments. In both habitats, nematode species richness and assemblage composition were not affected by the algae. The effect of C. cylindracea on the turnover and nestedness components of the Jaccard dissimilarity varied between the two habitats. We show that the presence of C. cylindracea gives rise to variable consequences on meiofauna biodiversity and C cycling in different habitats. We conclude that further studies across different habitats and ecological components are needed to ultimately understand and predict the consequences of C. cylindracea invasion in shallow Mediterranean ecosystems. PMID- 27258354 TI - Elucidation of the Metabolic Network of Helicobacter pylori J99 and Malaysian Clinical Strains by Phenotype Microarray. AB - BACKGROUND: Helicobacter pylori colonizes almost half of the human population worldwide. H. pylori strains are genetically diverse, and the specific genotypes are associated with various clinical manifestations including gastric adenocarcinoma, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). However, our current knowledge of the H. pylori metabolism is limited. To understand the metabolic differences among H. pylori strains, we investigated four Malaysian H. pylori clinical strains, which had been previously sequenced, and a standard strain, H. pylori J99, at the phenotypic level. MATERIALS AND METHODS: The phenotypes of the H. pylori strains were profiled using the Biolog Phenotype Microarray system to corroborate genomic data. We initiated the analyses by predicting carbon and nitrogen metabolic pathways from the H. pylori genomic data from the KEGG database. Biolog PM aided the validation of the prediction and provided a more intensive analysis of the H. pylori phenomes. RESULTS: We have identified a core set of metabolic nutrient sources that was utilized by all strains tested and another set that was differentially utilized by only the local strains. Pentose sugars are the preferred carbon nutrients utilized by H. pylori. The amino acids l-aspartic acid, d-alanine, and l asparagine serve as both carbon and nitrogen sources in the metabolism of the bacterium. CONCLUSION: The phenotypic profile based on this study provides a better understanding on the survival of H. pylori in its natural host. Our data serve as a foundation for future challenges in correlating interstrain metabolic differences in H. pylori. PMID- 27258355 TI - kmlShape: An Efficient Method to Cluster Longitudinal Data (Time-Series) According to Their Shapes. AB - BACKGROUND: Longitudinal data are data in which each variable is measured repeatedly over time. One possibility for the analysis of such data is to cluster them. The majority of clustering methods group together individual that have close trajectories at given time points. These methods group trajectories that are locally close but not necessarily those that have similar shapes. However, in several circumstances, the progress of a phenomenon may be more important than the moment at which it occurs. One would thus like to achieve a partitioning where each group gathers individuals whose trajectories have similar shapes whatever the time lag between them. METHOD: In this article, we present a longitudinal data partitioning algorithm based on the shapes of the trajectories rather than on classical distances. Because this algorithm is time consuming, we propose as well two data simplification procedures that make it applicable to high dimensional datasets. RESULTS: In an application to Alzheimer disease, this algorithm revealed a "rapid decline" patient group that was not found by the classical methods. In another application to the feminine menstrual cycle, the algorithm showed, contrarily to the current literature, that the luteinizing hormone presents two peaks in an important proportion of women (22%). PMID- 27258356 TI - Leiomyosarcoma of the inferior vena cava: Chasing the disease. PMID- 27258358 TI - Simultaneous bilateral tibial tubercle avulsion fracture in a male teenager: case report and literature review. AB - : Tibial tuberosity avulsion fractures are injuries accounting for less than 3% of all epiphyseal and 1% of all physeal injuries in adolescents. Bilateral injuries are very rare, with only 19 cases described in the literature. These types of fractures occur commonly in male teenagers during sport activities and are often associated with other orthopaedic disorders. We report the case of a male teenager with simultaneous bilateral tibial tubercle fractures, describe the evolution and treatment of this injury and review the literature on this subject. LEVEL OF EVIDENCE: Case report. PMID- 27258357 TI - Serological Evidence of Human Infection with Avian Influenza A H7virus in Egyptian Poultry Growers. AB - Avian influenza viruses circulate widely in birds, with occasional human infections. Poultry-exposed individuals are considered to be at high risk of infection with avian influenza viruses due to frequent exposure to poultry. Some avian H7 viruses have occasionally been found to infect humans. Seroprevalence of neutralizing antibodies against influenza A/H7N7 virus among poultry-exposed and unexposed individuals in Egypt were assessed during a three-years prospective cohort study. The seroprevalence of antibodies (titer, >=80) among exposed individuals was 0%, 1.9%, and 2.1% annually while the seroprevalence among the control group remained 0% as measured by virus microneutralization assay. We then confirmed our results using western blot and immunofluorescence assays. Although human infection with H7 in Egypt has not been reported yet, our results suggested that Egyptian poultry growers are exposed to avian H7 viruses. These findings highlight the need for surveillance in the people exposed to poultry to monitor the risk of zoonotic transmission of avian influenza viruses. PMID- 27258359 TI - Treatment of soft tissue defects in the heels of children in an emergency setting. AB - Reverse flow sural flap (RFSF) and vacuum sealing drainage (VSD) have been used to cover soft tissue defects in the heels of children in medical emergency settings. We report a retrospective case series, including a total of 19 children with soft tissue defects in heels resulting from spokes injury. In six patients, soft tissue defects in the heel were covered with RFSF. Further, in 13 patients, the defects were covered with VSD, in seven patients defects were repaired using free skin, and in six patients defects were repaired using RFSF after VSD. All wounds in the donor and recipient areas healed by first intention, and all free skins or island flaps completely survived; the color and luster on reconstructed areas were perfect. Patients were followed up for about 3-30 months, without osteomyelitis and infection in the heel, and the functions of the heel were satisfactory. RFSF and VSD were both advantageous, and were ideal for covering heel defects in children in emergency settings. PMID- 27258360 TI - Do additional full-length radiographs of the humerus and forearm improve the decision making in children with supracondylar humerus fractures? AB - We sought to determine the diagnostic utility of additional full-length radiographs of the forearm and humerus for pediatric supracondylar humerus fractures. A pediatric orthopedic surgeon and a senior orthopedic resident individually reviewed the initial humerus, forearm, and elbow radiographs of 55 children with a supracondylar humerus fracture and recommended definitive treatment (operative vs. nonoperative) on the basis of the modified Gartland classification. Interobserver agreements for classification and the recommended treatment were highest for the elbow radiographs (weighted kappa=0.92). All disagreements in the recommended treatment were in fractures classified as Gartland type I versus II fractures. Although two children (4%) had an ipsilateral distal forearm fracture, selective versus routine use of additional full-length radiographs in children with a supracondylar humerus fracture needs to be evaluated further. PMID- 27258361 TI - Percutaneous aspiration and irrigation technique for the treatment of pediatric septic hip: effectiveness and predictive parameters. AB - Septic arthritis of the hip has been treated traditionally by surgical drainage. Recent reports have described repeated aspirations as an adequate and safe treatment. The aim of the present study was to assess the success of treatment of septic arthritis of the hip by repeated aspirations and to identify predictive factors for failure. Medical records were retrospectively reviewed for all patients treated by ultrasound-guided aspiration and intravenous antibiotics between 2002 and 2010. The demographic, clinical, laboratory, and outcome data were recorded. Findings were compared between patients who responded to this treatment and those who subsequently required surgery. A total of 42 patients fulfilled the inclusion criteria. Of the total 33 responded to repeated aspirations and nine required surgical drainage. The mean age of patients requiring surgery was 8.3 years compared with 2.6 years for those responding to aspirations. Age older than 10 years was associated with a 57% rate of failed conservative treatment compared with 14% for age younger than 10 years. There was no significant difference between the groups in any of the other parameters measured. Follow-up of the operated group after an average of 7.44 years showed no unfavorable results. In children with septic arthritis of the hip, hip decompression may be achieved with repeated aspirations and lavage combined with antibiotics, sparing patients the risks of anesthesia and surgery. Age older than 10 years at admission may serve as the cutoff for initial conservative treatment. The postponement of surgery did not cause any long-term morbidity. LEVEL OF EVIDENCE: Level III; patients compared on the basis of outcome of conservative treatment of septic hip arthritis. PMID- 27258362 TI - Atelosteogenesis type III: orthopedic management. AB - Atelosteogenesis type III is a rare autosomal dominant skeletal dysplasia caused by mutations in the synthesis of the protein filamin B (FLNB). The mutation in the gene coding for FLNB causes the osteochondrodysplastic features of this disorder. Clinically, osteochondrodysplasia causes unbalanced skeletal maturation and absent or mostly hypoplastic bones, such as the pelvis, vertebrae, ribs, or long bones. In the literature, an orthopedic management for this disorder has not been well described. We report the case and orthopedic management of a 6-year-old female patient with atelosteogenesis type III after 3 years of follow-up. PMID- 27258363 TI - Outcome of the unaffected contralateral hip in unilateral slipped capital femoral epiphysis: a report comparing prophylactic fixation with observation. AB - This was a retrospective review of 80 patients with unilateral slipped capital femoral epiphysis treated with either prophylactic fixation or observation. The unaffected hip of 44 patients (mean age 12.6 years) were subjected to simultaneous prophylactic fixation and 36 patients (mean age 13.4 years) were managed by observation. Fisher's exact test showed a significantly high incidence of sequential slip of unaffected hips in the observation group in comparison with prophylactic fixation (P=0.002). No cases had avascular necrosis or chondrolysis. Prophylactic fixation significantly reduces the incidence of sequential slip. It outweighs the minimal surgical risks compared with its benefit in the prevention of further sequential slip. PMID- 27258364 TI - Craniocervical spinal instability after type 1 Arnold Chiari decompression: a case report. AB - To present and describe an unusual case of spinal instability after craniocervical spinal decompression for a type-1 Chiari malformation. Type-1 Chiari malformation is a craniocervical disorder characterized by tonsillar displacement greater than 5 mm into the vertebral canal; posterior fossa decompression is the most common surgical treatment for this condition. Postoperative complications have been described: cerebrospinal fluid leak, pseudomeningocele, aseptic meningitis, wound infection, and neurological deficit. However, instability after decompression is unusual. A 9-year-old female presented with symptomatic torticollis after cervical decompression for a type-1 Chiari malformation. Spinal instability was diagnosed; craniocervical stabilization was performed. After a 12-month follow-up, spinal stability was achieved, with a satisfactory clinical neck alignment. We present a craniocervical instability secondary to surgical decompression; clinical and radiological symptoms, and definitive treatment were described. PMID- 27258365 TI - Ultrastructure and Morphology of Compound Eyes of the Scorpionfly Panorpa dubia (Insecta: Mecoptera: Panorpidae). AB - Mecoptera are unique in holometabolous insects in that their larvae have compound eyes. In the present study the cellular organisation and morphology of the compound eyes of adult individuals of the scorpionfly Panorpa dubia in Mecoptera were investigated by light, scanning electron, and transmission electron microscopy. The results showed that the compound eyes of adult P. dubia are of the apposition type, each eye comprising more than 1200 ommatidia. The ommatidium consists of a cornea, a crystalline cone made up of four cone cells, eight photoreceptors, two primary pigment cells, and 18 secondary pigment cells. The adult ommatidium has a fused rhabdom with eight photoreceptors. Seven photoreceptors extend from the proximal end of the crystalline cone to the basal matrix, whereas the eighth photoreceptor is shorter, extending from the middle level of the photoreceptor cluster to the basal matrix. The fused rhabdom is composed of the rhabdomeres of different photoreceptors at different levels. The adult ommatidia have the same cellular components as the larval ommatidia, but the tiering scheme is different. PMID- 27258366 TI - Limited Top-Down Influence from Recognition to Same-Different Matching of Chinese Characters. AB - We investigated the extent to which recognition of Chinese characters influenced same-different matching performance that did not require recognition. In each experimental trial, two partially occluded characters were shown sequentially, and participants decided whether or not they were the same. The two characters were either both upright or both inverted and mirror-reflected. The participants' Chinese reading fluency spanned the full range, from not knowing any characters to native speakers. The participants who could recognize some characters (defined as readers) were subsequently tested with character recognition in a naming task. Interestingly, although the readers' recognition accuracies well correlated with their years of Chinese language schooling, they were uncorrelated with the matching accuracies in the same-different task with upright characters. The only indication of top-down influence was the readers' higher accuracy in matching upright than inverted and reflected characters. However, the magnitude of this effect was small, to the extent that the average same-different accuracies were comparable for readers and non-readers alike. This small effect was further confirmed with native speakers in China, who should give rise to the largest possible effect. We conclude that top-down influence from character recognition was present but very limited, at least with the task and stimuli used. PMID- 27258367 TI - Regioselective Radical Arylation of 3-Hydroxypyridines. AB - The titanium(III)-mediated radical arylation of 3-hydroxypyridines was found to proceed with high regioselectivity for the 2-position. Using aryldiazonium chlorides, which were prepared from the corresponding anilines, as aryl radical sources, a range of 3-hydroxy-2-phenylpyridines were obtained in moderate to good yields under simple reaction conditions. Reactions of ortho-carboxylic ester substituted phenyldiazonium salts directly provided tricyclic benzopyranopyridinones. PMID- 27258368 TI - Moving Beyond Active-Site Detection: MixMD Applied to Allosteric Systems. AB - Mixed-solvent molecular dynamics (MixMD) is a hotspot-mapping technique that relies on molecular dynamics simulations of proteins in binary solvent mixtures. Previous work on MixMD has established the technique's effectiveness in capturing binding sites of small organic compounds. In this work, we show that MixMD can identify both competitive and allosteric sites on proteins. The MixMD approach embraces full protein flexibility and allows competition between solvent probes and water. Sites preferentially mapped by probe molecules are more likely to be binding hotspots. There are two important requirements for the identification of ligand-binding hotspots: (1) hotspots must be mapped at very high signal-to-noise ratio and (2) the hotspots must be mapped by multiple probe types. We have developed our mapping protocol around acetonitrile, isopropanol, and pyrimidine as probe solvents because they allowed us to capture hydrophilic, hydrophobic, hydrogen-bonding, and aromatic interactions. Charged probes were needed for mapping one target, and we introduce them in this work. In order to demonstrate the robust nature and wide applicability of the technique, a combined total of 5 MUs of MixMD was applied across several protein targets known to exhibit allosteric modulation. Most notably, all the protein crystal structures used to initiate our simulations had no allosteric ligands bound, so there was no preorganization of the sites to predispose the simulations to find the allosteric hotspots. The protein test cases were ABL Kinase, Androgen Receptor, CHK1 Kinase, Glucokinase, PDK1 Kinase, Farnesyl Pyrophosphate Synthase, and Protein-Tyrosine Phosphatase 1B. The success of the technique is demonstrated by the fact that the top-four sites solely map the competitive and allosteric sites. Lower-ranked sites consistently map other biologically relevant sites, multimerization interfaces, or crystal-packing interfaces. Lastly, we highlight the importance of including protein flexibility by demonstrating that MixMD can map allosteric sites that are not detected in half the systems using FTMap applied to the same crystal structures. PMID- 27258369 TI - Short-Term Dynamic and Local Epidemiological Trends in the South American HIV-1B Epidemic. AB - The human displacement and sexual behavior are the main factors driving the HIV-1 pandemic to the current profile. The intrinsic structure of the HIV transmission among different individuals has valuable importance for the understanding of the epidemic and for the public health response. The aim of this study was to characterize the HIV-1 subtype B (HIV-1B) epidemic in South America through the identification of transmission links and infer trends about geographical patterns and median time of transmission between individuals. Sequences of the protease and reverse transcriptase coding regions from 4,810 individuals were selected from GenBank. Maximum likelihood phylogenies were inferred and submitted to ClusterPicker to identify transmission links. Bayesian analyses were applied only for clusters including >=5 dated samples in order to estimate the median maximum inter-transmission interval. This study analyzed sequences sampled from 12 South American countries, from individuals of different exposure categories, under different antiretroviral profiles, and from a wide period of time (1989-2013). Continentally, Brazil, Argentina and Venezuela were revealed important sites for the spread of HIV-1B among countries inside South America. Of note, from all the clusters identified about 70% of the HIV-1B infections are primarily occurring among individuals living in the same geographic region. In addition, these transmissions seem to occur early after the infection of an individual, taking in average 2.39 years (95% CI 1.48-3.30) to succeed. Homosexual/Bisexual individuals transmit the virus as quickly as almost half time of that estimated for the general population sampled here. Public health services can be broadly benefitted from this kind of information whether to focus on specific programs of response to the epidemic whether as guiding of prevention campaigns to specific risk groups. PMID- 27258370 TI - Regular Sputum Check-Up for Early Diagnosis of Tuberculosis after Exposure in Healthcare Facilities. AB - BACKGROUND: The early diagnosis of patients with TB disease is critical after an outbreak of tuberculosis (TB) infection in healthcare facilities. In this study, we report a catastrophic TB outbreak in a psychiatric healthcare facility and analyze the role of regular sputum check-ups and other diagnostic tools to facilitate an early diagnosis. METHODS: Every exposed participant received regular sputum check-ups and chest X-rays (CXR) as part of the outbreak management protocol. We retrospectively analyzed data from the contact participants to identify risk factors for eventual TB development and investigated the diagnostic efficacy of regular sputum check-ups. RESULTS: Among 133 contact participants, 16 (12.0%) developed TB during the 4-year follow-up period. Low body-mass-index (BMI) (<21) (adjusted hazard ratio (aHR) 3.16, 95% confidence interval (CI) 1.11-8.98) and long duration of contact (>3 months) (aHR 8.70, 95% CI, 1.14-63.34) independently predicted the development of TB. Even though regular sputum check-ups required significant resources, they did facilitate the early identification of new TB cases among the contact participants. Regular sputum check-ups for high-risk patients based on BMI, contact duration and CXR findings may be a practical approach when compared with universal sputum follow-up, with a slightly decreased sensitivity but high positive likelihood ratio (88%, [95% CI, 62-98%] and 5.12, [95%CI, 3.30-7.95], respectively). CONCLUSION: While regular sputum check-ups for all contact participants facilitated the early identification of cases after the outbreak of TB in the healthcare facility, regular sputum check-ups for high-risk patients might be an effective alternative in resource-limited settings. PMID- 27258371 TI - Contemporary clinical trial updates in heart failure. AB - PURPOSE OF REVIEW: Heart failure is a major source of cardiovascular morbidity and mortality worldwide. The field has benefited from steady progress, and there are now multiple strategies - medical and surgical - to improve cardiovascular outcomes. The quest continues for enhanced pathophysiologic insights and therapies. RECENT FINDINGS: The chosen studies highlight new ways of treating heart failure with reduced ejection fraction (HFrEF) with pharmacotherapy such as sacubitril/valsartan and explore the role of antimicrobial therapy for chronic Chagas' cardiomyopathy. The role of iron supplementation, spinal cord stimulation and gene therapy are evaluated. The treatment of heart failure with preserved ejection fraction (HFpEF) is scrutinized, and the role of nitrates is discussed. The use of left ventricular assist devices in wider populations of HFrEF patients is considered. SUMMARY: These pivotal contemporary trials will impact bedside management. Sacubitril/valsartan's mortality benefit in HFrEF and the negative effect of nitrates in HFpEF provide novel insights. Progress with durable mechanical circulatory support and nonpharmacological approaches to heart failure management expand therapeutic options. PMID- 27258372 TI - Statin myopathy: over-rated and under-treated? AB - PURPOSE OF REVIEW: Statins are recommended as first-line therapy for cardiovascular disease. Unfortunately, a proportion of patients cannot tolerate these drugs because of muscle-related side-effects. This review summarizes the definition of statin-related muscle disorders, aetiological factors, and recommended management strategies. RECENT FINDINGS: A number of consensus groups have defined and classified statin-related muscle disorders, whereas others have suggested diagnostic and management strategies. Mechanisms behind statin-related muscle toxicity have been identified. Therapeutic and clinical investigation pathways have been reviewed and algorithms defined. New drugs have become available to reduce low-density lipoprotein cholesterol levels that are not associated with causing muscle side-effects. SUMMARY: Statin-related muscle side effects are common. Secondary causes of muscle disease unmasked by statin therapy should be identified. Most patients can be managed by adjustment of standard treatment protocols. PMID- 27258374 TI - PrEP Awareness and Attitudes in a National Survey of Primary Care Clinicians in the United States, 2009-2015. AB - OBJECTIVES: As trials were assessing the safety and efficacy of daily oral antiretroviral preexposure prophylaxis (PrEP) for the prevention of HIV infection, there was a clear need to understand the evolution of knowledge of, and attitudes toward, PrEP among primary care clinicians. METHODS: Physicians and nurse practitioners were surveyed in 2009 (n = 1500), 2010 (n = 1504), 2012 (n = 1503), 2013 (n = 1507), 2014 (n = 1508) and 2015 (n = 1501) to assess their awareness of PrEP, willingness to prescribe PrEP, and whether they support use of public funds to pay for PrEP. Pharmacists (n = 251) were surveyed about PrEP in 2012 only. Descriptive statistics were computed for physician demographics and PrEP-related questions. Prevalence ratios for willingness to prescribe PrEP were computed using Poisson regression analysis. RESULTS: Awareness of PrEP was low among clinicians (2009: 24%, 2010: 29%) but increased after trials reported effectiveness (2012: 49%, 2013: 51%, 2014: 61%, 2015: 66%). Following a description of PrEP with an estimated effectiveness of 75%, across 6 of the study years 91% of clinicians indicated a willingness to prescribe PrEP to at least one group at high risk of HIV acquisition. A smaller majority of clinicians indicated support for public funding of PrEP in 2009: 59%, 2010: 53%, and 2013: 63%. CONCLUSIONS: In surveys conducted before and after the release of PrEP trial results, primary care clinicians were largely unaware of PrEP. They indicated high levels of willingness to prescribe it for patients at high risk of HIV acquisition and expressed interest in education about how to deliver this new clinical HIV prevention method. It will be important to continue monitoring clinician knowledge, attitudes, and practices as the use of PrEP increases in the US. PMID- 27258373 TI - Effects of Diets Supplemented with Ensiled Mulberry Leaves and Sun-Dried Mulberry Fruit Pomace on the Ruminal Bacterial and Archaeal Community Composition of Finishing Steers. AB - This study investigated the effects of ensiled mulberry leaves (EML) and sun dried mulberry fruit pomace (SMFP) on the ruminal bacterial and archaeal community composition of finishing steers. Corn grain- and cotton meal-based concentrate was partially replaced with EML or SMFP. The diets had similar crude protein (CP), neutral detergent fiber (NDF), and metabolizable energy. Following the feeding trial, the steers were slaughtered and ruminal liquid samples were collected to study the ruminal microbiome. Extraction of DNA, amplification of the V4 region of the 16S rRNA gene, and Illumina MiSeq pyrosequencing were performed for each sample. Following sequence de-noising, chimera checking, and quality trimming, an average of 209,610 sequences were generated per sample. Quantitative real-time PCR was performed to examine the selected bacterial species in the rumen. Our results showed that the predominant phyla were Bacteroidetes (43.90%), Firmicutes (39.06%), Proteobacteria (4.31%), and Tenericutes (2.04%), and the predominant genera included Prevotella (13.82%), Ruminococcus (2.51%), Butyrivibrio (2.38%), and Succiniclasticum (2.26%). Compared to the control group, EML and SMFP groups had a higher abundance of total bacteria (p < 0.001); however, the bacterial community composition was similar among the three groups. At the phylum level, there were no significant differences in Firmicutes (p = 0.7932), Bacteroidetes (p = 0.2330), Tenericutes (p = 0.2811), or Proteobacteria (p = 0.0680) levels among the three groups; however, Fibrobacteres decreased in EML (p = 0.0431). At the genus level, there were no differences in Prevotella (p = 0.4280), Ruminococcus (p = 0.2639), Butyrivibrio (p = 0.4433), or Succiniclasticum (p = 0.0431) levels among the groups. Additionally, the dietary treatments had no significant effects on the archaeal community composition in the rumen. Therefore, EML and SMFP supplementation had no significant effects on the ruminal bacterial or archaeal community composition of finishing steers. PMID- 27258375 TI - Speed of reversal of vecuronium neuromuscular block with different doses of neostigmine in anesthetized dogs. AB - OBJECTIVES: Neostigmine is routinely used to reverse non-depolarizing neuromuscular block. Given its indirect mechanism, a plateau may exist whereby increasing doses of neostigmine do not result in clinical benefit. This study was designed to measure the speed of reversal of vecuronium-induced neuromuscular block in isoflurane-anesthetized dogs after the administration of three doses of neostigmine as used in clinical practice. STUDY DESIGN: Prospective, crossover, randomized study. ANIMALS: Seven adult, mixed-breed dogs with a mean +/- standard deviation (SD) age of 2.0 +/- 0.8 years and weight of 19.1 +/- 9.1 kg. METHODS: Dogs were anesthetized on three occasions with isoflurane and administered vecuronium (0.1 mg kg-1) intravenously (IV). The train-of-four (TOF) ratio was measured on the pelvic limb with acceleromyography. When the second twitch of the TOF had returned spontaneously, atropine (0.03 mg kg-1) and neostigmine (0.02, 0.04 or 0.07 mg kg-1) were administered IV. Time to reach a TOF ratio of >=0.9 after neostigmine administration was recorded. RESULTS: Increasing the dose of neostigmine from 0.02 mg kg-1 to 0.04 mg kg-1 and 0.07 mg kg-1 resulted in significant reductions in mean +/- SD reversal times (10.5 +/- 2.3, 7.4 +/- 1.1 and 5.4 +/- 0.5 minutes, respectively) (p < 0.0001) and smaller coefficients of variation (22%, 15% and 10%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Increasing the dose of neostigmine from 0.02 mg kg-1 to 0.04 mg kg-1 and 0.07 mg kg-1 produced faster and less variable reversal of vecuronium-induced neuromuscular block in isoflurane-anesthetized dogs. No ceiling effect was observed at this dose range. PMID- 27258376 TI - Correction: Adipocytes as a Link Between Gut Microbiota-Derived Flagellin and Hepatocyte Fat Accumulation. AB - [This corrects the article DOI: 10.1371/journal.pone.0152786.]. PMID- 27258377 TI - Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age. AB - Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30-49 years, 86.5% and 94.7%; 50-69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age. PMID- 27258378 TI - A Behavioral Framework to Address the Emerging Challenge of Multimorbidity: Erratum. PMID- 27258383 TI - Correction: Brazil's Market for Trading Forest Certificates. AB - [This corrects the article DOI: 10.1371/journal.pone.0152311.]. PMID- 27258384 TI - Carbon Nanotubes as Electrically Active Nanoreactors for Multi-Step Inorganic Synthesis: Sequential Transformations of Molecules to Nanoclusters and Nanoclusters to Nanoribbons. AB - In organic synthesis, the composition and structure of products are predetermined by the reaction conditions; however, the synthesis of well-defined inorganic nanostructures often presents a significant challenge yielding nonstoichiometric or polymorphic products. In this study, confinement in the nanoscale cavities of single-walled carbon nanotubes (SWNTs) provides a new approach for multistep inorganic synthesis where sequential chemical transformations take place within the same nanotube. In the first step, SWNTs donate electrons to reactant iodine molecules (I2), transforming them to iodide anions (I(-)). These then react with metal hexacarbonyls (M(CO)6, M = Mo or W) in the next step, yielding anionic nanoclusters [M6I14](2-), the size and composition of which are strictly dictated by the nanotube cavity, as demonstrated by aberration-corrected high resolution transmission electron microscopy, scanning transmission electron microscopy, and energy dispersive X-ray spectroscopy. Atoms in the nanoclusters [M6I14](2-) are arranged in a perfect octahedral geometry and can engage in further chemical reactions within the nanotube, either reacting with each other leading to a new polymeric phase of molybdenum iodide [Mo6I12]n or with hydrogen sulfide gas giving rise to nanoribbons of molybdenum/tungsten disulfide [MS2]n in the third step of the synthesis. Electron microscopy measurements demonstrate that the products of the multistep inorganic transformations are precisely controlled by the SWNT nanoreactor with complementary Raman spectroscopy revealing the remarkable property of SWNTs to act as a reservoir of electrons during the chemical transformation. The electron transfer from the host nanotube to the reacting guest molecules is essential for stabilizing the anionic metal iodide nanoclusters and for their further transformation to metal disulfide nanoribbons synthesized in the nanotubes in high yield. PMID- 27258385 TI - Bias in Research Grant Evaluation Has Dire Consequences for Small Universities. AB - Federal funding for basic scientific research is the cornerstone of societal progress, economy, health and well-being. There is a direct relationship between financial investment in science and a nation's scientific discoveries, making it a priority for governments to distribute public funding appropriately in support of the best science. However, research grant proposal success rate and funding level can be skewed toward certain groups of applicants, and such skew may be driven by systemic bias arising during grant proposal evaluation and scoring. Policies to best redress this problem are not well established. Here, we show that funding success and grant amounts for applications to Canada's Natural Sciences and Engineering Research Council (NSERC) Discovery Grant program (2011 2014) are consistently lower for applicants from small institutions. This pattern persists across applicant experience levels, is consistent among three criteria used to score grant proposals, and therefore is interpreted as representing systemic bias targeting applicants from small institutions. When current funding success rates are projected forward, forecasts reveal that future science funding at small schools in Canada will decline precipitously in the next decade, if skews are left uncorrected. We show that a recently-adopted pilot program to bolster success by lowering standards for select applicants from small institutions will not erase funding skew, nor will several other post-evaluation corrective measures. Rather, to support objective and robust review of grant applications, it is necessary for research councils to address evaluation skew directly, by adopting procedures such as blind review of research proposals and bibliometric assessment of performance. Such measures will be important in restoring confidence in the objectivity and fairness of science funding decisions. Likewise, small institutions can improve their research success by more strongly supporting productive researchers and developing competitive graduate programming opportunities. PMID- 27258387 TI - Rotational Stability of Scaphoid Osteosyntheses: An In Vitro Comparison of Small Fragment Cannulated Screws to Novel Bone Screw Sets. AB - BACKGROUND: The current standard of care for operative repair of scaphoid fractures involves reduction and internal fixation with a single headless compression screw. However, a compression screw in isolation does not necessarily control rotational stability at a fracture or nonunion site. The single screw provides rotational control through friction and bone interdigitation from compression at the fracture site. We hypothesize that osteosyntheses with novel bone screw sets (BSS) equipped with anti-rotational elements provide improved rotational stability. METHODS: Stability of osteosynthesis under increasing cyclic torsional loading was investigated on osteotomized cadaveric scaphoids. Two novel prototype BSS, oblique type (BSS-obl.) and longitudinal type (BSS long.) were compared to three conventional screws: Acutrak2(r)mini, HCS(r)3.0 and Twinfix(r). Biomechanical tests were performed on scaphoids from single donors in paired comparison and analyzed by balanced incomplete random block design. Loading was increased by 50 mNm increments with 1,000 cycles per torque level and repeated until a rotational clearance of 10 degrees . Primary outcome measure was the number of cycles to 10 degrees clearance, secondary outcome measure was the maximum rotational clearance for each torque level. FINDINGS: BSS-obl. performed significantly better than Acutrak2(r)mini and HCS(r) (p = 0.015, p<0.0001). BSS long. performed significantly better than HCS(r) (p = 0.010). No significant difference in performance between BSS-obl. and BSS-long. (p = 0.361), between BSS obl. and Twinfix(r) (p = 0.50) and BSS long. and Twinfix(r) (p = 0.667) was detected. Within the torque range up to 200 mNm, four of 21 (19%) BSS-long. and four of 21 (19%) BSS-obl. preparations showed early failure. The same loading led to early failure in four (29%) Twinfix(r), seven (50%) Acutrak2(r)mini and 10 (71%) HCS(r) of 14 screw samples, respectively. CONCLUSIONS: For both BSS and to a lesser extent for Twinfix(r) (as dual-component screw), higher rotational stabilities were identified in comparison to single component headless compression screws. PMID- 27258386 TI - Transcriptome Analysis of the Sydney Rock Oyster, Saccostrea glomerata: Insights into Molluscan Immunity. AB - BACKGROUND: Oysters have important ecological functions in their natural environment, acting as global carbon sinks and improving water quality by removing excess nutrients from the water column. During their life-time oysters are exposed to a variety of pathogens that can cause severe mortality in a range of oyster species. Environmental stressors encountered in their habitat can increase the susceptibility of oysters to these pathogens and in general have been shown to impact on oyster immunity, making immune parameters expressed in these marine animals an important research topic. RESULTS: Paired-end Illumina high throughput sequencing of six S. glomerata tissues exposed to different environmental stressors resulted in a total of 484,121,702 paired-end reads. When reads and assembled transcripts were compared to the C. gigas genome, an overall low level of similarity at the nucleotide level, but a relatively high similarity at the protein level was observed. Examination of the tissue expression pattern showed that some transcripts coding for cathepsins, heat shock proteins and antioxidant proteins were exclusively expressed in the haemolymph of S. glomerata, suggesting a role in innate immunity. Furthermore, analysis of the S. glomerata ORFs showed a wide range of genes potentially involved in innate immunity, from pattern recognition receptors, components of the Toll-like signalling and apoptosis pathways to a complex antioxidant defence mechanism. CONCLUSIONS: This is the first large scale RNA-Seq study carried out in S. glomerata, showing the complex network of innate immune components that exist in this species. The results confirmed that many of the innate immune system components observed in mammals are also conserved in oysters; however, some, such as the TLR adaptors MAL, TRIF and TRAM are either missing or have been modified significantly. The components identified in this study could help explain the oysters' natural resilience against pathogenic microorganisms encountered in their natural environment. PMID- 27258390 TI - Fluoroform-Derived CuCF3 for Trifluoromethylation of Terminal and TMS-Protected Alkynes. AB - An efficient trifluoromethylation reaction of alkynes using a fluoroform-derived CuCF3 reagent is described. The CF3 source is the inexpensive industrial waste fluoroform (CF3H). The air-stable CuCF3 reagent can be prepared in large quantities and is convenient to use. Synthetically useful trifluoromethylated alkynes containing a wide range of functional groups were successfully synthesized under mild conditions. Both terminal and TMS-protected alkynes gave the products in one step. The beneficial effect of a diamine ligand tetramethylethylenediamine (TMEDA) with the fluoroform-derived CuCF3 reagent was also demonstrated. PMID- 27258388 TI - Discovery and Characterization of Phage Display-Derived Human Monoclonal Antibodies against RSV F Glycoprotein. AB - Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. The vast majority of neutralizing antibodies isolated from human subjects target the RSV fusion (F) glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. Currently, Synagis(r) (palivizumab) is the only FDA approved antibody drug for the prevention of RSV infection, and there is a great need for more effective vaccines and therapeutics. Phage display is a powerful tool in antibody discovery with the advantage that it does not require samples from immunized subjects. In this study, Morphosys HuCAL GOLD(r) phage libraries were used for panning against RSV prefusion and postfusion F proteins. Panels of human monoclonal antibodies (mAbs) against RSV F protein were discovered following phage library panning and characterized. Antibodies binding specifically to prefusion or postfusion F proteins and those binding both conformations were identified. 3B1 is a prototypic postfusion F specific antibody while 2E1 is a prototypic prefusion F specific antibody. 2E1 is a potent broadly neutralizing antibody against both RSV A and B strains. Epitope mapping experiments identified a conformational epitope spanning across three discontinuous sections of the RSV F protein, as well as critical residues for antibody interaction. PMID- 27258389 TI - Patterns and predictors of clustered risky health behaviors among adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. AB - BACKGROUND: Health complications related to childhood cancer may be influenced by risky health behaviors (RHBs), particularly when RHBs co-occur. To the authors' knowledge, only limited information is available describing how RHBs cluster among survivors of childhood cancer and their siblings and the risk factors for co-occurring RHBs. METHODS: Latent class analysis was used to identify RHB clusters using longitudinal survey data regarding smoking, alcohol use, and physical activity from adult survivors (4184 survivors) and siblings (1598 siblings) in the Childhood Cancer Survivor Study. Generalized logistic regression was used to evaluate associations between demographic characteristics, treatment exposures, psychological distress, health conditions, and cluster membership. RESULTS: Three RHB clusters were identified: a low-risk cluster, an insufficiently active cluster, and a high-risk cluster (tobacco and risky alcohol use and insufficient activity). Compared with siblings, survivors were more likely to be in the insufficiently active cluster (adjusted odds ratio [ORadj ], 1.17; 95% confidence interval [95% CI], 1.06-1.27) and were less likely to be in the high-risk cluster (ORadj , 0.79; 95% CI, 0.69-0.88). Risk factors for membership in the high-risk cluster included psychological distress (ORadj , 2.76; 95% CI, 1.98-3.86), low educational attainment (ORadj , 7.49; 95% CI, 5.15 10.88), income <$20,000 (ORadj , 2.62; 95% CI, 1.93-3.57), being divorced/separated or widowed (ORadj , 1.36; 95% CI, 1.03-1.79), and limb amputation (ORadj , 1.52; 95% CI, 1.03-2.24). Risk factors for the insufficiently active cluster included chronic health conditions, psychological distress, low education or income, being obese or overweight, female sex, nonwhite race/ethnicity, single marital status, cranial radiation, and cisplatin exposure. CONCLUSIONS: RHBs co-occur in survivors of childhood cancer and their siblings. Economic and educational disadvantages and psychological distress should be considered in screening and interventions to reduce RHBs. Cancer 2016. (c) 2016 American Cancer Society. Cancer 2016;122:2747-2756. (c) 2016 American Cancer Society. PMID- 27258391 TI - Effects of Nutrient Loading and Mercury Chemical Speciation on the Formation and Degradation of Methylmercury in Estuarine Sediment. AB - Net formation of methylmercury (MeHg) in sediments is known to be affected by the availability of inorganic divalent mercury (Hg(II)) and by the activities of Hg(II) methylating and MeHg demethylating bacteria. Enhanced autochthonous organic matter deposition to the benthic zone, following increased loading of nutrients to the pelagic zone, has been suggested to increase the activity of Hg(II) methylating bacteria and thus the rate of net methylation. However, the impact of increased nutrient loading on the biogeochemistry of mercury (Hg) is challenging to predict as different geochemical pools of Hg may respond differently to enhanced bacterial activities. Here, we investigate the combined effects of nutrient (N and P) supply to the pelagic zone and the chemical speciation of Hg(II) and of MeHg on MeHg formation and degradation in a brackish sediment-water mesocosm model ecosystem. By use of Hg isotope tracers added in situ to the mesocosms or ex situ in incubation experiments, we show that the MeHg formation rate increased with nutrient loading only for Hg(II) tracers with a high availability for methylation. Tracers with low availability did not respond significantly to nutrient loading. Thus, both microbial activity (stimulated indirectly through plankton biomass production by nutrient loading) and Hg(II) chemical speciation were found to control the MeHg formation rate in marine sediments. PMID- 27258393 TI - Covalent EGFR Inhibitors: Binding Mechanisms, Synthetic Approaches, and Clinical Profiles. AB - Being overexpressed in several types of cancer, the epidermal growth factor receptor (EGFR) is considered one of the key therapeutic targets in oncology. Although many first-generation EGFR inhibitors had been FDA approved for the treatment of certain types of cancer, patients soon developed resistance to these reversible ATP competitive inhibitors via mutations in the kinase domain of EGFR. A new trend was adopted to design covalent irreversible inhibitors, that is, second- and third-generation inhibitors. Second-generation inhibitors can inhibit the mutant forms but, unfortunately, they had dose limiting side effects due to wild-type EGFR inhibition. Third-generation inhibitors emerged shortly, which were capable of inhibiting the mutant forms exclusively while sparing the wild type. Many other strategies have also been developed to reduce the risk of covalent interactions with off-targets, thus improving the pharmacokinetic and/or pharmacodynamic profile of the antiproliferative agents. In this review, we focused mainly on second- and third-generation EGFR inhibitors, their binding mechanisms (either docking studies or co-crystallized structures), their synthetic approaches, clinical profiles, and limitations. PMID- 27258394 TI - Minimization of Surface Energies and Ripening Outcompete Template Effects in the Surface Growth of Metal-Organic Frameworks. AB - As well-oriented, surface-bound metal-organic frameworks become the centerpiece of many new applications, a profound understanding of their growth mode becomes necessary. This work shows that the currently favored model of surface templating is in fact a special case valid only for systems with a more or less cubic crystal shape, while in less symmetric systems crystal ripening and minimization of surface energies dominate the growth process. PMID- 27258395 TI - (Multiple) Isotope probing approaches to trace the fate of environmental chemicals and the formation of non-extractable 'bound' residues. AB - Procedures for the analysis of turnover of chemicals (and of natural compounds) are well developed using radio or stable isotope labelled tracer compounds in various standardized OECD tests. Due to the analytical focus on the isotope label the chemical speciation of the so-called non-extractable residues (NER) in soils and sediments often remains unknown. These NER may stem from parent compounds, metabolites, microbial biomass, or from precipitated carbonates after productive microbial degradation. Fate studies mostly do not describe the link to phylogenetic assignment of degraders and microbial ecology although in these fields various isotope tracer applications are well developed, too. We present several options for integrating both approaches in environmental biotechnology and how they can be used to improve knowledge in microbial ecology. PMID- 27258392 TI - Physiological, pathological, and engineered cell identity reprogramming in the central nervous system. AB - Multipotent neural stem cells persist in restricted regions of the adult mammalian central nervous system. These proliferative cells differentiate into diverse neuron subtypes to maintain neural homeostasis. This endogenous process can be reprogrammed as a compensatory response to physiological cues, traumatic injury, and neurodegeneration. In addition to innate neurogenesis, recent research has demonstrated that new neurons can be engineered via cell identity reprogramming in non-neurogenic regions of the adult central nervous system. A comprehensive understanding of these reprogramming mechanisms will be essential to the development of therapeutic neural regeneration strategies that aim to improve functional recovery after injury and neurodegeneration. WIREs Dev Biol 2016, 5:499-517. doi: 10.1002/wdev.234 For further resources related to this article, please visit the WIREs website. PMID- 27258396 TI - Attenuated SIV causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic antiretroviral therapy. AB - OBJECTIVES: Using simian models, where SIV chronic viral loads are naturally controlled in the absence of potentially neurotoxic therapies, we investigated the neuropathological events occurring during times of suppressed viraemia and when these events were initiated. DESIGN: Cynomolgus macaques were infected with SIV strains that are naturally controlled to low levels of chronic viraemia. Study 1: animals were maintained up to 300 days after inoculation and analysed for viral-induced neuropathology following sustained suppression of chronic viral loads. Study 2: initiation and development of lesion was examined following 3, 10, 21, or 125 days SIVmacC8 infection. METHODS: Formalin-fixed, paraffin embedded brain sections were analysed following immunohistochemical staining for simian immunodeficiency virus (SIV) (KK41), blood-brain barrier leakage (ZO-1, fibrinogen), apoptosis (active caspase 3), neuroinflammation [GFAP, cyclooxygenase (COX)-1, COX-2], microglia and macrophage (Iba-1, CD68, and CD16), oligodendrocytes (CNPase1), MHC class II expression, and T cells (CD3 and CD8). Replicating SIV was detected through in-situ hybridization. RESULTS: Study 1: neuroinflammation was present despite prolonged suppressed viraemia. Study 2: attenuated SIV entered the brain rapidly triggering acute phase neuroinflammatory responses. These did not return to naive levels and GFAP and COX-2 responses continued to develop during a chronic phase with a suppressed viral load. CONCLUSION: Neuroinflammatory responses similar to those in HIV neurocognitively impaired patients are present within macaque brains during prolonged periods of suppressed SIV viral load and in the absence of potentially neurotoxic antiretroviral drugs. These responses, initiated during acute infection, do not resolve despite the lack of on-going peripheral viraemia to potentially reseed the brain. PMID- 27258397 TI - Probability of N332 glycan occupancy on HIV-1 gp120 modulates sensitivity to broadly neutralizing antibodies. AB - OBJECTIVE(S): The glycan shield of the HIV-1 envelope glycoprotein complex (Env), in particular the glycan at position 332 in gp120, is frequently targeted by broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals. We investigated the role of the second amino acid position of the N332 glycosylation motif Asn-X-Ser in HIV-1 evolution and neutralization sensitivity. DESIGN AND METHODS: Viral variants harbouring glycosylation motifs with different probabilities of glycan occupancy were tested for their sensitivity to a subset of N332-dependent bNAbs. Furthermore, longitudinal Env sequences of 37 HIV-1 infected individuals were used to analyse the evolution of the N332 glycosylation motif within these individuals. Finally, early Env sequences from 31 historical and 21 contemporaneous seroconverters were compared to analyse this evolution on a population level. RESULTS: Viral variants with a higher probability of N332 occupancy were more sensitive to neutralization by some N332-dependent bNAbs. Furthermore, the longitudinal analyses revealed an increase in probability of glycan occupancy of the N332 site over time, both within patients, and at the population level over the course of 20 years of HIV-1 epidemic. CONCLUSIONS: These observations suggest that modulation of N332 glycan occupancy by the second amino acid position of the canonical glycosylation motif Asn-X-Ser plays a previously unappreciated role in viral escape from immune responses, and should be considered in Env-based vaccine design. PMID- 27258398 TI - T-cell receptor transfer for boosting HIV-1-specific T-cell immunity in HIV-1 infected patients. AB - OBJECTIVES: Strategies to cure HIV-1 infection require the eradication of viral reservoirs. An innovative approach for boosting the cytotoxic T-lymphocyte response is the transfer of T-cell receptors (TCRs). Previously, we have shown that electroporation of TCR-encoding mRNA is able to reprogram CD8 T cells derived from healthy donors. So far, it is unknown whether the transfer of HIV-1 specific TCRs is capable to reprogram CD8 T cells of HIV-1-infected patients. To assess the efficiency of TCR-transfer by mRNA electroporation and the functionality of reprogramed T cells in HIV-1-infected patients, we performed an in-vitro analysis of TCR-transfer into T cells from HIV-1-infected patients in various stages of disease and from healthy controls. METHODS: Peripheral blood mononuclear cells from 16 HIV-1-infected patients (nine HLA-A02-positive, seven HLA-A02-negative) and from five healthy controls were electroporated with mRNA constructs encoding TCRs specific for the HLA-A02/HIV-1-gag p17 epitope SLYNTVATL (SL9). Functionality of the TCRs was measured by gammaIFN-ELISpot assays. RESULTS: SL9/TCR transfection into peripheral blood mononuclear cells from both HLA-A02-positive and HLA-A02-negative HIV-1-infected patients and from healthy blood donors reprogramed T cells for recognition of SL9-presenting HLA-A02 positive cells in gammaIFN-ELISpot assays. SL9/TCR-transfer into T cells from an immunodeficient AIDS patient could induce recognition of SL9-expressing target cells only after reversion of T-cell dysfunction by antiretroviral therapy. CONCLUSION: The transfer of HIV-1-p17-specific TCRs into T cells is functional both in HIV-1-infected patients as well as in healthy blood donors. TCR-transfer is a promising method to boost the immune system against HIV-1. PMID- 27258399 TI - Increased adolescent HIV testing with a hybrid mobile strategy in Uganda and Kenya. AB - OBJECTIVE: We sought to increase adolescent HIV testing across rural communities in east Africa and identify predictors of undiagnosed HIV. DESIGN: Hybrid mobile testing. METHODS: We enumerated 116 326 adolescents (10-24 years) in 32 communities of Uganda and Kenya ( SEARCH: NCT01864603): 98 694 (85%) reported stable (>=6 months of prior year) residence. In each community we performed hybrid testing: 2-week multidisease community health campaign that included HIV testing, followed by home-based testing of community health campaign nonparticipants. We measured adolescent HIV testing coverage and prevalence, and determined predictors of newly diagnosed HIV among HIV-infected adolescents using multivariable logistic regression. RESULTS: A total of 86 421 (88%) stable adolescents tested for HIV; coverage was 86, 90, and 88% in early (10-14), mid (15-17), and late (18-24) adolescents, respectively. Self-reported prior testing was 9, 26, and 55% in early, mid, and late adolescents tested, respectively. HIV prevalence among adolescents tested was 1.6 and 0.6% in Ugandan women and men, and 7.1 and 1.5% in Kenyan women and men, respectively. Prevalence increased in mid-adolescence for women and late adolescence for men. Among HIV-infected adolescents, 58% reported newly diagnosed HIV. In multivariate analysis of HIV infected adolescents, predictors of newly diagnosed HIV included male sex [odds ratio (OR) = 1.97 (95% confidence interval (CI): 1.42-2.73)], Ugandan residence [OR = 2.63 (95% CI: 2.08-3.31)], and single status [OR = 1.62 (95% CI: 1.23-2.14) vs. married)]. CONCLUSIONS: The SEARCH hybrid strategy tested 88% of stable adolescents for HIV, a substantial increase over the 28% reporting prior testing. The majority (57%) of HIV-infected adolescents were new diagnoses. Mobile HIV testing for adults should be leveraged to reach adolescents for HIV treatment and prevention. PMID- 27258401 TI - From Natural Product to the First Oral Treatment for Multiple Sclerosis: The Discovery of FTY720 (GilenyaTM)? AB - Multiple sclerosis is a devastating chronic autoimmune disease affecting women and men of all ages. Inflammation of the central nervous system causes demyelination and ultimately neuropsychological dysfunction. Myriocin, a natural product with strong immunosuppressant activity was interrogated leading to a new class of immunomodulator with a unique mode of action. In this review, we will summarize these findings, the mechanism hypothesis and discuss the data's ultimately leading to the approval of GilenyaTM as the first oral treatment for multiple sclerosis. PMID- 27258400 TI - A Tunable Scaffold of Microtubular Graphite for 3D Cell Growth. AB - Aerographite (AG) is a novel carbon-based material that exists as a self supportive 3D network of interconnected hollow microtubules. It can be synthesized in a variety of architectures tailored by the growth conditions. This flexibility in creating structures presents interesting bioengineering possibilities such as the generation of an artificial extracellular matrix. Here we have explored the feasibility and potential of AG as a scaffold for 3D cell growth employing cyclic RGD (cRGD) peptides coupled to poly(ethylene glycol) (PEG) conjugated phospholipids for surface functionalization to promote specific adhesion of fibroblast cells. Successful growth and invasion of the bulk material was followed over a period of 4 days. PMID- 27258402 TI - Hybrid Nanoparticles as Drug Carriers for Controlled Chemotherapy of Cancer. AB - Rapid developments in materials science and biological mechanisms have greatly boosted the research discoveries of new drug delivery systems. In the past few decades, hundreds of nanoparticle-based drug carriers have been reported almost on a daily basis, in which new materials, structures, and mechanisms are proposed and evaluated. Standing out among the drug carriers, the hybrid nanoparticle systems offer a great opportunity for the optimization and improvement of conventional chemotherapy. By combining several features of functional components, these hybrid nanoparticles have shown excellent promises of improved biosafety, biocompatibility, multifunctionality, biodegradability, and so forth. In this Personal Account, we highlight the recent research advances of some representative hybrid nanoparticles as drug delivery systems and discuss their design strategies and responsive mechanisms for controlled drug delivery. PMID- 27258403 TI - The Association between Nutritional Markers and Biochemical Parameters and Residual Renal Function in Peritoneal Dialysis Patients. AB - Residual renal function (RRF) is an important prognostic factor for peritoneal dialysis patients as it influences the quality of life and mortality. This study was conducted to explore the potential factors correlated with RRF. A cross sectional study was conducted by recruiting 155 patients with residual GFR more than 1mL/min per 1.73m2 at the initiation of peritoneal dialysis. We collected the demographic characteristics, nutritional markers and biochemical parameters of all participants, and analyzed the correlation between these variables and residual GFR as well. The odds ratio of RRF loss associated with each of the nutritional markers and biochemical parameters were estimated by logistic regression model. The residual GFR was negatively correlated with serum phosphate (ORQ3 = 2.67, 95%CI: 1.03-6.92; ORQ4 = 3.45, 95%CI: 1.35-9.04), magnesium (ORQ4 = 3.77, 95%CI: 1.48-3.63), and creatinine (ORQ3 = 2.93, 95%CI: 1.09-7.88; ORQ4 = 8.64 95%CI: 2.79-26.78), while positively associated with normalized protein catabolic rate (ORQ3 = 0.24, 95%CI: 0.09-0.65; ORQ4 = 0.11, 95%CI: 0.03-0.35), 24 hours urine volume(ORQ1 = 22.87, 95%CI: 2.76-189.24; ORQ3 = 0.08, 95%CI: 0.02 0.28) and serum chlorine concentrations (ORQ1 = 5.34, 95%CI: 1.94-14.68; ORQ4 = 0.28, 95%CI: 0.09-0.85), respectively. Our study suggested that the nutritional markers and biochemical parameters, though not all, but at least in part were closely correlated with RRF in peritoneal dialysis patients. PMID- 27258404 TI - Chinese Herbal Medicine Image Recognition and Retrieval by Convolutional Neural Network. AB - Chinese herbal medicine image recognition and retrieval have great potential of practical applications. Several previous studies have focused on the recognition with hand-crafted image features, but there are two limitations in them. Firstly, most of these hand-crafted features are low-level image representation, which is easily affected by noise and background. Secondly, the medicine images are very clean without any backgrounds, which makes it difficult to use in practical applications. Therefore, designing high-level image representation for recognition and retrieval in real world medicine images is facing a great challenge. Inspired by the recent progress of deep learning in computer vision, we realize that deep learning methods may provide robust medicine image representation. In this paper, we propose to use the Convolutional Neural Network (CNN) for Chinese herbal medicine image recognition and retrieval. For the recognition problem, we use the softmax loss to optimize the recognition network; then for the retrieval problem, we fine-tune the recognition network by adding a triplet loss to search for the most similar medicine images. To evaluate our method, we construct a public database of herbal medicine images with cluttered backgrounds, which has in total 5523 images with 95 popular Chinese medicine categories. Experimental results show that our method can achieve the average recognition precision of 71% and the average retrieval precision of 53% over all the 95 medicine categories, which are quite promising given the fact that the real world images have multiple pieces of occluded herbal and cluttered backgrounds. Besides, our proposed method achieves the state-of-the-art performance by improving previous studies with a large margin. PMID- 27258405 TI - Does adding endometrial scratching to diagnostic hysteroscopy improve pregnancy rates in women with recurrent in-vitro fertilization failure? AB - OBJECTIVE: To investigate the effect of additional endometrial scratching procedure during hysteroscopy on assisted reproductive technology (ART) cycle outcomes in repeated implantation failure (RIF) patients without endometrial or uterine abnormalities on hysteroscopic evaluation. MATERIALS AND METHODS: Three hundred and forty-five RIF patients who underwent ART at a university-based infertility clinic between January 2011 and June 2015 were recruited in this retrospective cohort study. Uterine cavities of all included patients were evaluated by diagnostic hysteroscopy 7-14 days prior to the subsequent ART cycle. Women without endometrial abnormalities were allocated into two groups; the scratching group was consisted of patients who underwent endometrial scratching by using monopolar electric energy with needle forceps during hysteroscopy, and the control group was consisted of patients who underwent only diagnostic hysteroscopy. RESULTS: The implantation rate was significantly higher in the scratching group than the control group (37.7% versus 24.5%; p = 0.04). Clinical and ongoing pregnancy rates were also found to be significantly higher in the scratching group than the control group (37.7% versus 27.6%; p = 0.03; and 33.3% versus 23%; p = 0.03, respectively). CONCLUSION: Endometrial scratching during diagnostic hysteroscopy seems to enhance implantation and as well pregnancy rates in comparison to diagnostic hysteroscopy alone. PMID- 27258406 TI - Detection of Ophidiomyces, the Causative Agent of Snake Fungal Disease, in the Eastern Massasauga ( Sistrurus catenatus ) in Michigan, USA, 2014. AB - Snake fungal disease (SFD), caused by Ophidiomyces ophiodiicola, threatens free ranging snake populations across the US. We assayed 112 swabs from 102 individual eastern massasaugas ( Sistrurus catenatus ) at three locations in Michigan in 2014 for Ophidiomyces using quantitative PCR (qPCR). We observed a 12.7% qPCR prevalence of skin lesions. Individuals at each site had lesions, and occurrence of skin lesions was not significantly different between sites. We detected Ophidiomyces DNA at each of the three sites in five individuals (4.9%). We found no difference in detection probabilities between sites; however, snakes with dermatitis had higher Ophidiomyces DNA detection probabilities (P=0.15+/-0.08 SE) than snakes without dermatitis (P=0.02+/-0.01 SE, P=0.026). The emergence of SFD mortalities has potentially serious consequences for the viability of the eastern massasauga in Michigan. Future work should track temporal patterns in vital rates and health parameters, link health data to body condition indices for individual snakes, and conduct a "hotspot" analysis to examine health on a landscape scale. PMID- 27258407 TI - Waterbird Susceptibility to Avian Cholera at Hayward Marsh, California, USA. AB - We characterized past avian cholera outbreaks in waterbirds at Hayward Marsh, California, US. In 2013, we surveyed populations and determined the presence of disease using several diagnostic methods, including behavioral and physical observations, field necropsy, and bacterial culture. We compiled this information with data from previous outbreaks from 1990-2012 to compare waterbird abundance to various measures of mortality, including percentage of mortality and percentage of difference between abundance and mortality by species. We suggest that Ruddy Duck ( Oxyura jamaicensis ) have consistently suffered greater mortality from this disease than have other species at this site. PMID- 27258408 TI - Characterization of Leptospira santarosai Serogroup Grippotyphosa Serovar Bananal Isolated from Capybara ( Hydrochaeris hydrochaeris ) in Brazil. AB - Leptospirosis is a widespread zoonosis caused by bacteria of the genus Leptospira. Rodents appear to be the most important reservoirs of infection. They contaminate the environment and food and can transmit the pathogen when they are consumed by carnivores. Capybara ( Hydrochaeris hydrochaeris ) are efficient reservoirs of Leptospira, and because they are in close contact with farm animals and are found in semiurban areas, they represent a risk to public health. We isolated five Leptospira strains from capybara kidneys in Sao Paulo State, Brazil, in 2001 and typed them using serologic and molecular techniques. These strains include the Leptospira santarosai serogroup Grippotyphosa serovar Bananal. Pulsed field gel electrophoresis resulted in a unique pattern distinct from the reference strains, and the isolates clustered with greater than 85% similarity. The isolates also presented higher growth rates than other Leptospira serovars, with high minimal inhibitory concentration values for most of the tested antibiotics, with the exception of penicillin and ampicillin. This isolation and characterization of the L. santarosai serogroup Grippotyphosa serovar Bananal from capybara, highlights the importance of wild and sinantropic rodents as carriers of pathogenic leptospires. PMID- 27258409 TI - Seoul virus in the Brown Rat ( Rattus norvegicus ) from Urumqi, Xinjiang, Northwest of China. AB - Hantavirus infections among human populations are linked to the geographic distribution of the host rodents that carry the viruses. To determine the presence and distribution of hantaviruses in the northern region of Xinjiang Uygur Autonomous Region (XUAR), northwestern China, 844 rodents were captured from five locations in four dissimilar habitats during 2010-14 and examined for Hantavirus infection. Hantavirus nucleic acids were firstly detected in the brown rat ( Rattus norvegicus ) from Urumqi, China, indicating that the Hantavirus was transmitted into Urumqi in XUAR and circulated by the brown rat. Our results suggest that the brown rat may act as a natural reservoir for the virus in XUAR. PMID- 27258410 TI - Exploring factors related to the anger superiority effect in children with Autism Spectrum Disorder. AB - Despite face and emotion recognition deficits, individuals with Autism Spectrum Disorder (ASD) appear to experience the anger superiority effect, where an angry face in a crowd is detected faster than a neutral face. This study extended past research to examine the impacts of ecologically valid photographic stimuli, gender and anxiety symptoms on the anger superiority effect in children with and without ASD. Participants were 81, 7-12year old children, 42 with ASD matched on age, gender and perceptual IQ to 39 typically developing (TYP) children. The photographic stimuli did not impact on task performance in ASD with both groups exhibiting the anger superiority effect. There were no gender differences and no associations with anxiety. Age was associated with the effect in the TYP but not ASD group. These findings confirm a robust effect of speeded detection of threat in ASD which does not appear to be confounded by gender or anxiety, but may have different underlying age-associated mechanisms. PMID- 27258411 TI - Gravity matters: Motion perceptions modified by direction and body position. AB - Motion coherence thresholds are consistently higher at lower velocities. In this study we analysed the influence of the position and direction of moving objects on their perception and thereby the influence of gravity. This paradigm allows a differentiation to be made between coherent and randomly moving objects in an upright and a reclining position with a horizontal or vertical axis of motion. 18 young healthy participants were examined in this coherent threshold paradigm. Motion coherence thresholds were significantly lower when position and motion were congruent with gravity independent of motion velocity (p=0.024). In the other conditions higher motion coherence thresholds (MCT) were found at lower velocities and vice versa (p<0.001). This result confirms previous studies with higher MCT at lower velocity but is in contrast to studies concerning perception of virtual turns and optokinetic nystagmus, in which differences of perception were due to different directions irrespective of body position, i.e. perception took place in an egocentric reference frame. Since the observed differences occurred in an upright position only, perception of coherent motion in this study is defined by an earth-centered reference frame rather than by an ego-centric frame. PMID- 27258412 TI - Alterations in Phase-Related Prefrontal Activation During Cognitive Tasks and Nicotinic alpha4beta2 Receptor Availability in Alzheimer's Disease. AB - BACKGROUND: Evidence shows that the cholinergic system plays an important role in regulating working memory and that working memory-related prefrontal activation decreases with age and neuronal degeneration, such as Alzheimer's disease (AD). However, the relation between attention-related alpha4beta2 nicotinic cholinergic function and task-induced prefrontal activation especially time course-related activation remains to be explored. OBJECTIVE: We aimed to elucidate the relationship between changes in task-induced oxy-hemoglobin concentration (cerebral blood flow, CBF) in the prefrontal cortex and the availability of alpha4beta2 nicotinic receptors in the brain of AD patients in light of their task performance. METHODS: Eleven mild-to-moderate AD patients and eleven normal elderly subjects underwent the near-infrared spectroscopy during easy and difficult working memory tasks for estimating prefrontal CBF changes and positron emission tomography with the alpha4beta2 tracer [18F]2FA-85380 ([18F]2FA) for measuring the alpha4beta2 nicotinic receptor binding. RESULTS: Significant correlations between mean oxy-hemoglobin concentration in the channels with significant [group] main effects and prefrontal [18F]2FA binding were observed during the early easy task period in the normal group and during the late difficult task in the AD group. In addition, those prefrontal CBF responses were significantly correlated with not correct performance but the execution time to spend. CONCLUSION: The alpha4beta2 nicotinic acetylcholine receptors in the prefrontal cortex play an important role in increasing prefrontal activation when attending to novel stimuli, irrespective of the accuracy of the outcome. A delay in the cholinergic-induced increase in prefrontal activation in AD patients might explain their delayed responses in the cognitive task. PMID- 27258413 TI - A Novel Splice-Acceptor Site Mutation in GRN (c.709-2 A>T) Causes Frontotemporal Dementia Spectrum in a Large Family from Southern Italy. AB - Heterozygous loss of function mutations in granulin represent a significant cause of frontotemporal lobar degeneration with ubiquitin and TDP-43 inclusions (FTLD TDP). We report a novel GRN splice site mutation (c.709-2 A>T), segregating with frontotemporal dementia spectrum in a large family from southern Italy. The GRN c.709-2 A>T is predicted to result in the skipping of exon 8, leading to non sense mediated mRNA decay. Moreover, the PGRN plasma levels in the GRN c.709-2 A>T carriers were significantly lower (24 ng/ml) compared to controls (142.7 ng/ml) or family members non-carriers (82.0 ng/ml) (p-value = 0.005, Kruskal Wallis), suggesting progranulin haploinsufficiency. We do not report any potential pathogenic GRN mutation in a follow-up cohort composed of 6 FTD families and 43 sporadic FTD cases, from the same geographic area. Our study suggests that GRN (c.709-2 A>T) is a novel and likely very rare cause of FTD in this Italian cohort. Finally, in line with previous studies, we show that GRN haploinsufficiency leads to a heterogeneous clinical picture, and plasma progranulin levels may be a reliable tool to identify GRN loss of function mutations. However, given that a) genetic and environmental factors, gender, and age may regulate PGRN plasma levels and b) plasma progranulin levels may not reflect PGRN levels in the central nervous system, we suggest that the measurement of progranulin in the plasma should always be coupled with genetic screening of GRN for mutations. PMID- 27258414 TI - Non-Fibrillar Oligomeric Amyloid-beta within Synapses. AB - Alzheimer's disease (AD) is characterized by memory loss, insidious cognitive decline, profound neurodegeneration, and the extracellular accumulation of amyloid-beta (Abeta) peptide in senile plaques and intracellular accumulation of tau in neurofibrillary tangles. Loss and dysfunction of synapses are believed to underlie the devastating cognitive decline in AD. A large amount of evidence suggests that oligomeric forms of Abeta associated with senile plaques are toxic to synapses, but the precise sub-synaptic localization of Abeta and which forms are synaptotoxic remain unknown. Here, we characterize the sub-synaptic localization of Abeta oligomers using three high-resolution imaging techniques, stochastic optical reconstruction microscopy, immunogold electron microscopy, and Forster resonance energy transfer in a plaque-bearing mouse model of AD. With all three techniques, we observe oligomeric Abeta inside synaptic terminals. Further, we tested a panel of Abeta antibodies using the relatively high-throughput array tomography technique to determine which forms are present in synapses. Our results show that different oligomeric Abeta species are present in synapses and highlight the potential of array tomography for rapid testing of aggregation state specific Abeta antibodies in brain tissue. PMID- 27258415 TI - The Longitudinal Association Between a Discrepancy Measure of Anosognosia in Patients with Dementia, Caregiver Burden and Depression. AB - BACKGROUND: According to cross-sectional studies, there is an association between anosognosia in people with dementia and caregiver's burden and depression. Anosognosia in patients may be a cause of caregiver burden and depression. However, variability in caregiver anosognosia ratings may exist as caregivers with burden and depression may have a more pessimistic view of the patients' health. OBJECTIVE: To assess the variability of caregiver anosognosia ratings of patients with dementia using a widely used anosognosia scale and its longitudinal relationship with caregiver burden and depression. METHODS: A convenience cohort of 221 consecutive dementia outpatient and caregiver dyads was followed up at 12 and 24 months. The main instruments used were the Anosognosia Questionnaire Dementia (AQ-D), Caregiver Burden Interview, and Geriatric Depression Scale. Linear mixed models were used including time as a factor in every model. Multivariate analyses controlled for caregiver's socio-demographic and possible confounding factors. RESULTS: Attrition at 12 and 24 months was 24.9% and 42.5% respectively. Patients at baseline were on average 77.8 years of age, 63.3% were women, and 63.3% had < 5 years of education. In the bivariate analyses, caregiver burden, depression, and gender were associated with caregiver ratings of total, cognitive, and personality AQ-D of the patient at different time points. Multivariate analyses revealed burden as the caregiver variable most consistently associated with total, cognitive, and personality caregiver AQ-D ratings of the patient. CONCLUSION: Some caregiver characteristics, especially burden, are associated with caregiver ratings of AQ-D with regard to the patient. PMID- 27258416 TI - Expression Pattern of Scavenger Receptors and Amyloid-beta Phagocytosis of Astrocytes and Microglia in Culture are Modified by Acidosis: Implications for Alzheimer's Disease. AB - The pathological hallmarks of Alzheimer's disease (AD) are amyloid-beta (Abeta) plaques, neurofibrillary tangles, and glia activation. The pathology also includes vascular amyloidosis and cerebrovascular disease. Vascular compromise can result in hypoperfusion, local tissue hypoxia, and acidosis. Activated microglia and astrocytes can phagocytose Abeta through membrane receptors that include scavenger receptors. Changes in glial cells induced by extracellular acidosis could play a role in the development of AD. Here, we assess whether extracellular acidosis changes glial cell properties relevant for Abeta clearance capacity. Incubation of glial cells on acidified culture medium (pH 6.9 or 6.5) for 24-48 h resulted in decreased cell diameter, with thinner branches in astrocytes, slight reduction in cell body size in microglia, a transient decrease in astrocyte adhesion to substrates, and a persistent decrease in microglia adhesion compared with control media (pH 7.4). Astrocyte Abeta phagocytosis decreased at pH 6.9 and 6.5, whereas microglia phagocytosis only transiently decreased in acidified media. Scavenger receptors class B member I (SR-BI) increased and scavenger receptors-macrophage receptors with collagenous structures (SR-MARCO) decreased in astrocytes cultured at pH 6.5. In contrast, in microglia exposed to pH 6.5, expression of SR-BI and SR-MARCO increased and fatty acid translocase (CD-36) decreased. In conclusion, the acidic environment changed the adhesiveness and morphology of both microglia and astrocytes, but only astrocytes showed a persistent decrease in Abeta clearance activity. Expression of scavenger receptors was affected differentially in microglia and astrocytes by acidosis. These changes in scavenger receptor patterns can affect the activation of glia and their contribution to neurodegeneration. PMID- 27258418 TI - Uncovering the Neural Bases of Cognitive and Affective Empathy Deficits in Alzheimer's Disease and the Behavioral-Variant of Frontotemporal Dementia. AB - Loss of empathy is a core presenting feature of the behavioral-variant of frontotemporal dementia (bvFTD), resulting in socioemotional difficulties and behavioral transgressions. In contrast, interpersonal functioning remains relatively intact in Alzheimer's disease (AD), despite marked cognitive decline. The neural substrates mediating these patterns of loss and sparing in social functioning remain unclear, yet are relevant for our understanding of the social brain. We investigated cognitive versus affective aspects of empathy using the Interpersonal Reactivity Index (IRI) in 25 AD and 24 bvFTD patients and contrasted their performance with 22 age- and education-matched controls. Cognitive empathy was comparably compromised in AD and bvFTD, whereas affective empathy was impaired exclusively in bvFTD. While controlling for overall cognitive dysfunction ameliorated perspective-taking deficits in AD, empathy loss persisted across cognitive and affective domains in bvFTD. Voxel-based morphometry analyses revealed divergent neural substrates of empathy loss in each patient group. Perspective-taking deficits correlated with predominantly left sided temporoparietal atrophy in AD, whereas widespread bilateral frontoinsular, temporal, parietal, and occipital atrophy was implicated in bvFTD. Reduced empathic concern in bvFTD was associated with atrophy in the left orbitofrontal, inferior frontal, and insular cortices, and the bilateral mid-cingulate gyrus. Our findings suggest that social cognitive deficits in AD arise largely as a consequence of global cognitive dysfunction, rather than a loss of empathy per se. In contrast, loss of empathy in bvFTD reflects the deterioration of a distributed network of frontoinsular and temporal structures that appear crucial for monitoring and processing social information. PMID- 27258417 TI - Review of the Evidence that Transcranial Electromagnetic Treatment will be a Safe and Effective Therapeutic Against Alzheimer's Disease. AB - We have demonstrated in multiple studies that daily, long-term electromagnetic field (EMF) treatment in the ultra-high frequency range not only protects Alzheimer's disease (AD) transgenic mice from cognitive impairment, but also reverses such impairment in aged AD mice. Moreover, these beneficial cognitive effects appear to be through direct actions on the AD process. Based on a large array of pre-clinical data, we have initiated a pilot clinical trial to determine the safety and efficacy of EMF treatment to mild-moderate AD subjects. Since it is important to establish the safety of this new neuromodulatory approach, the main purpose of this review is to provide a comprehensive assessment of evidence supporting the safety of EMFs, particularly through transcranial electromagnetic treatment (TEMT). In addition to our own pre-clinical studies, a rich variety of both animal and cell culture studies performed by others have underscored the anticipated safety of TEMT in clinical AD trials. Moreover, numerous clinical studies have determined that short- or long-term human exposure to EMFs similar to those to be provided clinically by TEMT do not have deleterious effects on general health, cognitive function, or a variety of physiologic measures-to the contrary, beneficial effects on brain function/activity have been reported. Importantly, such EMF exposure has not been shown to increase the risk of any type of cancer in human epidemiologic studies, as well as animal and cell culture studies. In view of all the above, clinical trials of safety/efficacy with TEMT to AD subjects are clearly warranted and now in progress. PMID- 27258419 TI - Neurodegeneration-Like Pathological and Behavioral Changes in an AAV9-Mediated p25 Overexpression Mouse Model. AB - BACKGROUND: The transgenic mice models overexpressing human p25 contribute greatly to the in vivo neurotoxic mechanism of p25 in neurodegenerative diseases. However, it is time-consuming to manipulate existing transgenic mice models. OBJECTIVE: Here we aim to establish a novel mouse model of neurodegeneration by overexpressing p25 mediated by recombinant adeno-associated virus serotype 9 (rAAV9). METHODS: AAV9-GFP-p25 encoding GFP-fused p25 driven by synapsin promoter, and the control, AAV9-GFP, were delivered in mice by tail-vein injection. Assessments of p25 expression, neurodegenerative pathology, and behavioral changes were performed. RESULTS: GFP expression was detected by in vivo imaging as early as one week after virus injection. Notably, widespread expression of p25 was obviously found in cortex, hippocampus, and cerebellum in AAV9-GFP-p25 mice. Moreover, decreased hippocampus volumes in AAV9-GFP-p25 mice were detected by 7T MRI examination about one month after injection. Further, these AAV9-GFP-p25 mice exhibited progressive memory impairment from three-month to six-month after virus injection. At last, hyperphosphorylated tau, neurofibrillary tangles, activated astrocytes and microglia cells were elevated in these p25 mice at about six months after virus delivery. However, amyloid-beta plaques, overt neuronal loss, and apoptosis in the hippocampus and cortex were not significantly induced by AAV9-mediated p25 overexpression. CONCLUSION: The AAV9-mediated p25 overexpression mouse model, which is a practical model exhibiting neurodegeneration-like pathological and behavioral changes, provides an easier and time-saving method to explore the functions of p25 in vivo, as well as an alternative tool for development of drugs against neurotoxic of p25. PMID- 27258421 TI - Measurement Error, Reliability, and Minimum Detectable Change in the Mini-Mental State Examination, Montreal Cognitive Assessment, and Color Trails Test among Community Living Middle-Aged and Older Adults. AB - BACKGROUND: Knowing the reliability of cognitive tests, particularly those commonly used in clinical practice, is important in order to interpret the clinical significance of a change in performance or a low score on a single test. OBJECTIVE: To report the intra-class correlation (ICC), standard error of measurement (SEM) and minimum detectable change (MDC) for the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Color Trails Test (CTT) among community dwelling older adults. METHODS: 130 participants aged 55 and older without severe cognitive impairment underwent two cognitive assessments between two and four months apart. Half the group changed rater between assessments and half changed time of day. RESULTS: Mean (standard deviation) MMSE was 28.1 (2.1) at baseline and 28.4 (2.1) at repeat. Mean (SD) MoCA increased from 24.8 (3.6) to 25.2 (3.6). There was a rater effect on CTT, but not on the MMSE or MoCA. The SEM of the MMSE was 1.0, leading to an MDC (based on a 95% confidence interval) of 3 points. The SEM of the MoCA was 1.5, implying an MDC95 of 4 points. MoCA (ICC = 0.81) was more reliable than MMSE (ICC = 0.75), but all tests examined showed substantial within-patient variation. CONCLUSION: An individual's score would have to change by greater than or equal to 3 points on the MMSE and 4 points on the MoCA for the rater to be confident that the change was not due to measurement error. This has important implications for epidemiologists and clinicians in dementia screening and diagnosis. PMID- 27258420 TI - Increased Expression of Readthrough Acetylcholinesterase Variants in the Brains of Alzheimer's Disease Patients. AB - Alzheimer's disease (AD) is characterized by a decrease in the enzymatic activity of the enzyme acetylcholinesterase (AChE). AChE is expressed as multiple splice variants, which may serve both cholinergic degradative functions and non cholinergic functions unrelated with their capacity to hydrolyze acetylcholine. We have recently demonstrated that a prominent pool of enzymatically inactive AChE protein exists in the AD brain. In this study, we analyzed protein and transcript levels of individual AChE variants in human frontal cortex from AD patients by western blot analysis using specific anti-AChE antibodies and by quantitative real-time PCR (qRT-PCR). We found similar protein and mRNA levels of the major cholinergic "tailed"-variant (AChE-T) and the anchoring subunit, proline-rich membrane anchor (PRiMA-1) in frontal cortex obtained from AD patients and non-demented controls. Interestingly, we found an increase in the protein and transcript levels of the non-cholinergic "readthrough" AChE (AChE-R) variants in AD patients compared to controls. Similar increases were detected by western blot using an antibody raised against the specific N-terminal domain, exclusive of alternative N-extended variants of AChE (N-AChE). In accordance with a subset of AChE-R monomers that display amphiphilic properties that are upregulated in the AD brain, we demonstrate that the increase of N-AChE species is due, at least in part, to N-AChE-R variants. In conclusion, we demonstrate selective alterations in specific AChE variants in AD cortex, with no correlation in enzymatic activity. Therefore, differential expression of AChE variants in AD may reflect changes in the pathophysiological role of AChE, independent of cholinergic impairment or its role in degrading acetylcholine. PMID- 27258422 TI - Outstanding Phenotypic Differences in the Profile of Amyloid-beta between Tg2576 and APPswe/PS1dE9 Transgenic Mouse Models of Alzheimer's Disease. AB - APPswe/PS1dE9 and Tg2576 are very common transgenic mouse models of Alzheimer's disease (AD), used in many laboratories as tools to research the mechanistic process leading to the disease. In order to augment our knowledge about the amyloid-beta (Abeta) isoforms present in both transgenic mouse models, we have developed two chromatographic methods, one acidic and the other basic, for the characterization of the Abeta species produced in the brains of the two transgenic mouse models. After immunoprecipitation and micro-liquid chromatography-electrospray ionization mass spectrometry/mass spectrometry, 10 species of Abeta, surprisingly all of human origin, were detected in the brain of Tg2576 mouse, whereas 39 species, of both murine and human origin, were detected in the brain of the APP/PS1 mouse. To the best of our knowledge, this is the first study showing the identification of such a high number of Abeta species in the brain of the APP/PS1 transgenic mouse, whereas, in contrast, a much lower number of Abeta species were identified in the Tg2576 mouse. Therefore, this study brings to light a relevant phenotypic difference between these two popular mice models of AD. PMID- 27258423 TI - Optimized Standard Operating Procedures for the Analysis of Cerebrospinal Fluid Abeta42 and the Ratios of Abeta Isoforms Using Low Protein Binding Tubes. AB - BACKGROUND: Reduced cerebrospinal fluid (CSF) concentration of amyloid-beta1-42 (Abeta1-42) reflects the presence of amyloidopathy in brains of subjects with Alzheimer's disease (AD). OBJECTIVE: To qualify the use of Abeta1-42/Abeta1-40 for improvement of standard operating procedures (SOP) for measurement of CSF Abeta with a focus on CSF collection, storage, and analysis. METHODS: Euroimmun ELISAs for CSF Abeta isoforms were used to set up a SOP with respect to recipient properties (low binding, polypropylene), volume of tubes, freeze/thaw cycles, addition of detergents (Triton X-100, Tween-20) in collection or storage tubes or during CSF analysis. Data were analyzed with linear repeated measures and mixed effects models. RESULTS: Optimization of CSF analysis included a pre-wash of recipients (e.g., tubes, 96-well plates) before sample analysis. Using the Abeta1 42/Abeta1-40 ratio, in contrast to Abeta1-42, eliminated effects of tube type, additional freeze/thaw cycles, or effect of CSF volumes for polypropylene storage tubes. 'Low binding' tubes reduced the loss of Abeta when aliquoting CSF or in function of additional freeze/thaw cycles. Addition of detergent in CSF collection tubes resulted in an almost complete absence of variation in function of collection procedures, but affected the concentration of Abeta isoforms in the immunoassay. CONCLUSION: The ratio of Abeta1-42/Abeta1-40 is a more robust biomarker than Abeta1-42 toward (pre-) analytical interfering factors. Further, 'low binding' recipients and addition of detergent in collection tubes are able to remove effects of SOP-related confounding factors. Integration of the Abeta1 42/Abeta1-40 ratio and 'low-binding tubes' into guidance criteria may speed up worldwide standardization of CSF biomarker analysis. PMID- 27258425 TI - Best Linear Unbiased Prediction of Individual Polygenic Susceptibility to Sporadic Vascular Dementia. AB - Genetic factors of sporadic vascular dementia have been quite limitedly understood. Many underlying polygenes are suspected to contribute to susceptibility to sporadic vascular dementia as a typical complex disease although they have not been identified from genome-wide association studies. This study suggests a stochastic prediction of individual polygenetic susceptibility to sporadic vascular dementia using best linear unbiased prediction in a mixed model framework. The prediction shows a relative degree of individual genetic susceptibility to the disease that reflects its integrative polygenetic factors across the genome. The estimate should take into account heritability and the prevalence of sporadic vascular dementia to cope with the disease. This offers a model for application of a genetic blueprint for a complex disease to personalized preventive medicine. PMID- 27258424 TI - Sideritis spp. Extracts Enhance Memory and Learning in Alzheimer's beta Amyloidosis Mouse Models and Aged C57Bl/6 Mice. AB - Nowadays, Alzheimer's disease is the most prevalent epiphenomenon of the aging population. Although soluble amyloid-beta (Abeta) species (monomers, oligomers) are recognized triggers of the disease, no therapeutic approach is able to stop it. Herbal medicines are used to treat different diseases in many regions of the world. On the Balkan Peninsula, at the eastern Mediterranean Sea, and adjacent regions, Sideritis species are used as traditional medicine to prevent age related problems in elderly. To evaluate this traditional knowledge in controlled experiments, we tested extracts of two commonly used Sideritis species, Sideritis euboea and Sideritis scardica, with regard to their effects on cognition in APP transgenic and aged, non-transgenic C57Bl/6 mice. Additionally, histomorphological and biochemical changes associated with Abeta deposition and treatment were assessed. We found that daily oral treatment with Sideritis spp. extracts highly enhanced cognition in aged, non-transgenic as well as in APP transgenic mice, an effect that was even more pronounced when extracts of both species were applied in combination. The treatment strongly reduced Abeta42 load in APP-transgenic mice, accompanied by increased phagocytic activity of microglia, and increased expression of the alpha-secretase ADAM10. Moreover, the treatment was able to fully rescue neuronal loss of APP-transgenic mice to normal levels as seen in non-transgenic controls. Having the traditional knowledge in mind, our results imply that treatment with Sideritis spp. extracts might be a potent, well-tolerated option for treating symptoms of cognitive impairment in elderly and with regard to Alzheimer's disease by affecting its most prominent hallmarks: Abeta pathology and cognitive decline. PMID- 27258426 TI - Aggression, Violence and Injury in Minor League Ice Hockey: Avenues for Prevention of Injury. AB - BACKGROUND: In North America, more than 800,000 youth are registered in organized ice hockey leagues. Despite the many benefits of involvement, young players are at significant risk for injury. Body-checking and aggressive play are associated with high frequency of game-related injury including concussion. We conducted a qualitative study to understand why youth ice hockey players engage in aggressive, injury-prone behaviours on the ice. METHODS: Semi-structured interviews were conducted with 61 minor ice hockey participants, including male and female players, parents, coaches, trainers, managers and a game official. Players were aged 13-15 playing on competitive body checking teams or on non-body checking teams. Interviews were manually transcribed, coded and analyzed for themes relating to aggressive play in minor ice hockey. RESULTS: Parents, coaches, teammates and the media exert a large influence on player behavior. Aggressive behavior is often reinforced by the player's social environment and justified by players to demonstrate loyalty to teammates and especially injured teammates by seeking revenge particularly in competitive, body-checking leagues. Among female and male players in non-body checking organizations, aggressive play is not reinforced by the social environment. These findings are discussed within the framework of social identity theory and social learning theory, in order to understand players' need to seek revenge and how the social environment reinforces aggressive behaviors. CONCLUSION: This study provides a better understanding of the players' motivations and environmental influences around aggressive and violent play which may be conducive to injury. The findings can be used to help design interventions aimed at reducing aggression and related injuries sustained during ice hockey and sports with similar cultures and rules. PMID- 27258427 TI - Bis-clickable Mesoporous Silica Nanoparticles: Straightforward Preparation of Light-Actuated Nanomachines for Controlled Drug Delivery with Active Targeting. AB - Bis(clickable) mesoporous silica nanospheres (ca. 100 nm) were obtained by the co condensation of TEOS with variable amounts (2-5 % each) of two clickable organosilanes in the presence of CTAB. Such nanoparticles could be easily functionalized with two independent functions using the copper-catalyzed alkyne azide cycloaddition (CuAAC) reaction to transform them into nanomachines bearing cancer cell targeting ligands with the ability to deliver drugs on-demand. The active targeting was made possible after anchoring folic acid by CuAAC click reaction, whereas the controlled delivery was performed by clicked azobenzene fragments. Indeed, the azobenzene groups are able to obstruct the pores of the nanoparticles in the dark whereas upon irradiation in the UV or in the blue range, their trans-to-cis photoisomerization provokes disorder in the pores, enabling the delivery of the cargo molecules. The on-command delivery was proven in solution by dye release experiments, and in vitro by doxorubicin delivery. The added value of the folic acid ligand was clearly evidenced by the difference of cell killing induced by doxorubicin-loaded nanoparticles under blue irradiation, depending on whether the particles featured the clicked folic acid ligand or not. PMID- 27258428 TI - Histones Induce the Procoagulant Phenotype of Endothelial Cells through Tissue Factor Up-Regulation and Thrombomodulin Down-Regulation. AB - The high circulating levels of histones found in various thrombotic diseases may compromise the anticoagulant barrier of endothelial cells. We determined how histones affect endothelial procoagulant tissue factor (TF) and anticoagulant thrombomodulin (TM). Surface antigens, soluble forms, and mRNA levels of TF and TM were measured by flow cytometry, ELISA, and real-time RT-PCR, respectively. TF and TM activity were measured using procoagulant activity, thrombin generation, or chromogenic assays. Involvement of the toll-like receptor (TLR) was assessed using the neutralizing antibodies. Histones dose-dependently induced surface antigens, activity and mRNA levels of endothelial TF. Histone-treated endothelial cells significantly shortened the lag time and enhanced the endogenous thrombin potential of normal plasma, which was normalized by a TF neutralizing antibody. Histones induced phosphatidylserine and protein-disulfide isomerase expression in endothelial cells. Histones also reduced the surface antigen, activity, and mRNA levels of endothelial TM. Polysialic acid and heparin reversed the histone induced TF up-regulation and TM down-regulation. Activated protein C did not affect the TF up-regulation, but interrupted TM down-regulation. TLR2, and TLR4 inhibitors partially blocked the TF up-regulation. Histones induced the endothelial procoagulant phenotype through TF up-regulation and TM down regulation. The effects of histones were partly mediated by TLR2, TLR4. Strategies to inhibit the harmful effects of histones in endothelial cells may be required in order to prevent a thrombotic environment. PMID- 27258429 TI - Motorists' knowledge, attitudes and practices toward alcohol-impaired driving/riding in Ghana. AB - OBJECTIVES: The main objective of this study was to establish the knowledge, attitudes, and practices toward drink driving/riding as a risk factor for road traffic crashes in 3 regional capitals in Ghana. METHODS: The study used a face to-face approach to randomly sample motorists who were accessing various services at fuel/gas stations, garages, and lorry terminals in 3 cities in Ghana. RESULTS: Over the previous 12 months, 24% of all motorists and 55% of motorists who were current alcohol users reported driving or riding a vehicle within an hour of alcohol intake. On average, motorists/riders who were current alcohol users consumed 4 standard drinks per drinking occasion. Generally, 83% of motorists who currently use alcohol walked, rode, or drove home after consuming alcohol away from their homes. Motorists/riders who reported drink driving were 4 times more likely to have had previous traffic violation arrests compared to those who reported no drink driving/riding (P =.001). Respondents were of the opinion that speeding was the major cause of traffic crashes, followed by driver carelessness, poor road conditions, inexperienced driving, and drink driving, in that order. Thirty-six percent of motorists who use alcohol had the perception that consuming between 6 and 15 standard drinks was the volume of alcohol that will take them to the legal blood alcohol concentration (BAC) limit of 0.08%. Compared to females, male motorists/riders were more likely to report drink driving (adjusted odds ratio [AOR] = 5.15; 95% confidence interval [CI], 2.31 to 11.47). Private motorists also reported a higher likelihood of drink driving compared to commercial drivers (AOR = 3.36; 95% CI, 1.88 to 6.02). Only 4% of motorists knew the legal BAC limit of Ghana and only 2% had ever been tested for drink driving/riding. CONCLUSION: The volumes of alcohol that motorists typically consume per drinking occasion were very high and their estimates of the number of drinks required to reach the legal BAC limit was also very high. Provision of authoritative information advising motorists about safe, responsible, or low-risk levels of alcohol consumption is imperative. Many traffic violations including drink driving were reported, thus suggesting a need for enhanced policing and enforcement. However, given the low level of knowledge of the legal BAC limit, educating motorists about how many drinks will approximate the legal BAC should be intensified prior to an increase in enforcement; otherwise, the desired outcome of enforcement may not be achieved. PMID- 27258431 TI - Notice of Retraction: Sato Y, et al. The Prevention of Hip Fracture With Risedronate and Ergocalciferol Plus Calcium Supplementation in Elderly Women With Alzheimer Disease: A Randomized Controlled Trial. Arch Intern Med. 2005;165(15):1737-1742. PMID- 27258430 TI - Access to HIV care in the context of universal test and treat: challenges within the ANRS 12249 TasP cluster-randomized trial in rural South Africa. AB - INTRODUCTION: We aimed to quantify and identify associated factors of linkage to HIV care following home-based HIV counselling and testing (HBHCT) in the ongoing ANRS 12249 treatment-as-prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. METHODS: Individuals >=16 years were offered HBHCT; those who were identified HIV positive were referred to cluster-based TasP clinics and offered antiretroviral treatment (ART) immediately (five clusters) or according to national guidelines (five clusters). HIV care was also available in the local Department of Health (DoH) clinics. Linkage to HIV care was defined as TasP or DoH clinic attendance within three months of referral among adults not in HIV care at referral. Associated factors were identified using multivariable logistic regression adjusted for trial arm. RESULTS: Overall, 1323 HIV-positive adults (72.9% women) not in HIV care at referral were included, of whom 36.9% (n=488) linked to care <3 months of referral (similar by sex). In adjusted analyses (n=1222), individuals who had never been in HIV care before referral were significantly less likely to link to care than those who had previously been in care (<33% vs. >42%, p<0.001). Linkage to care was lower in students (adjusted odds-ratio [aOR]=0.47; 95% confidence interval [CI] 0.24-0.92) than in employed adults, in adults who completed secondary school (aOR=0.68; CI 0.49-0.96) or at least some secondary school (aOR=0.59; CI 0.41-0.84) versus <= primary school, in those who lived at 1 to 2 km (aOR=0.58; CI 0.44-0.78) or 2-5 km from the nearest TasP clinic (aOR=0.57; CI 0.41-0.77) versus <1 km, and in those who were referred to clinic after >=2 contacts (aOR=0.75; CI 0.58-0.97) versus those referred at the first contact. Linkage to care was higher in adults who reported knowing an HIV-positive family member (aOR=1.45; CI 1.12-1.86) versus not, and in those who said that they would take ART as soon as possible if they were diagnosed HIV positive (aOR=2.16; CI 1.13-4.10) versus not. CONCLUSIONS: Fewer than 40% of HIV positive adults not in care at referral were linked to HIV care within three months of HBHCT in the TasP trial. Achieving universal test and treat coverage will require innovative interventions to support linkage to HIV care. PMID- 27258432 TI - Massage with or without aromatherapy for symptom relief in people with cancer. AB - BACKGROUND: Massage and aromatherapy massage are used to relieve cancer-related symptoms. A number of claims have been made for these treatments including reduction of pain, anxiety, depression, and stress. Other studies have not shown these benefits. OBJECTIVES: To evaluate the effects of massage with or without aromatherapy on pain and other symptoms associated with cancer. SEARCH METHODS: We searched the following databases and trials registries up to August 2015: the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 7), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), PubMed Cancer Subset, SADCCT, and the World Health Organization (WHO) ICTRP. We also searched clinical trial registries for ongoing studies. SELECTION CRITERIA: Randomised controlled studies (RCTs) reporting the effects of aromatherapy or massage therapy, or both, in people with cancer of any age. We applied no language restrictions. Comparators were massage (using carrier oil only) versus no massage, massage with aromatherapy (using carrier oil plus essential oils) versus no massage, and massage with aromatherapy (using carrier oil plus essential oils) versus massage without aromatherapy (using carrier oil only). DATA COLLECTION AND ANALYSIS: At least two review authors selected studies, assessed the risk of bias, and extracted data relating to pain and other symptoms associated with cancer, using standardised forms. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created two 'Summary of findings' tables. MAIN RESULTS: We included 19 studies (21 reports) of very low quality evidence with a total of 1274 participants. We included 14 studies (16 reports) in a qualitative synthesis and five studies in a quantitative synthesis (meta-analysis). Thirteen studies (14 reports, 596 participants) compared massage with no massage. Six studies (seven reports, 561 participants) compared aromatherapy massage with no massage. Two studies (117 participants) compared massage with aromatherapy and massage without aromatherapy. Fourteen studies had a high risk of bias related to sample size and 15 studies had a low risk of bias for blinding the outcome assessment. We judged the studies to be at unclear risk of bias overall. Our primary outcomes were pain and psychological symptoms. Two studies reported physical distress, rash, and general malaise as adverse events. The remaining 17 studies did not report adverse events. We downgraded the GRADE quality of evidence for all outcomes to very low because of observed imprecision, indirectness, imbalance between groups in many studies, and limitations of study design. Massage versus no-massage groupsWe analysed results for pain and anxiety but the quality of evidence was very low as most studies were small and considered at an unclear or high risk of bias due to poor reporting. Short-term pain (Present Pain Intensity-Visual Analogue Scale) was greater for the massage group compared with the no-massage group (one RCT, n = 72, mean difference (MD) -1.60, 95% confidence interval (CI) -2.67 to -0.53). Data for anxiety (State-Trait Anxiety Inventory-state) relief showed no significant difference in anxiety between the groups (three RCTs, n = 98, combined MD -5.36, 95% CI -16.06 to 5.34). The subgroup analysis for anxiety revealed that the anxiety relief for children was greater for the massage group compared with the no-massage group (one RCT, n = 30, MD -14.70, 95% CI -19.33 to 10.07), but the size of this effect was considered not clinically significant. Furthermore, this review demonstrated no differences in effects of massage on depression, mood disturbance, psychological distress, nausea, fatigue, physical symptom distress, or quality of life when compared with no massage. Massage with aromatherapy versus no-massage groupsWe analysed results for pain, anxiety, symptoms relating to the breast, and quality of life but the quality of evidence was very low as studies were generally at a high risk of bias. There was some indication of benefit in the aromatherapy-massage group but this benefit is unlikely to translate into clinical benefit. The relief of medium- and long-term pain (medium-term: one RCT, n = 86, MD 5.30, 95% CI 1.52 to 9.08; long-term: one RCT, n = 86, MD 3.80, 95% CI 0.19 to 7.41), anxiety (two RCTs, n = 253, combined MD -4.50, 95% CI -7.70 to -1.30), and long-term symptoms relating to the breast in people with breast cancer (one RCT, n = 86, MD -9.80, 95% CI -19.13 to -0.47) was greater for the aromatherapy-massage group, but the results were considered not clinically significant. The medium-term quality of life score was lower (better) for the aromatherapy-massage group compared with the no-massage group (one RCT, n = 30, MD -2.00, 95% CI -3.46 to -0.54). Massage with aromatherapy versus massage without aromatherapy groupsFrom the limited evidence available, we were unable to assess the effect of adding aromatherapy to massage on the relief of pain, psychological symptoms including anxiety and depression, physical symptom distress, or quality of life. AUTHORS' CONCLUSIONS: There was a lack of evidence on the clinical effectiveness of massage for symptom relief in people with cancer. Most studies were too small to be reliable and key outcomes were not reported. Any further studies of aromatherapy and massage will need to address these concerns. PMID- 27258433 TI - Intraocular Pharmacokinetics of Intravitreal Aflibercept (Eylea) in a Rabbit Model. AB - PURPOSE: We determined the intraocular pharmacokinetic properties of intravitreally injected aflibercept (Eylea) in a rabbit model. METHODS: Aflibercept was injected intravitreally in 21 eyes from New Zealand White rabbits. The eyes were enucleated 1, 24, 48, 120, 216, 360, and 720 hours (1, 2, 5, 9, 15, and 30 days, respectively) after injection and immediately frozen at 80 degrees C. The concentrations of aflibercept in the vitreous, aqueous humor, and retina/choroid were determined by performing an indirect enzyme-linked immunosorbent assay, and analyzed to understand the pharmacokinetic properties of the drug. RESULTS: The maximum concentration of aflibercept was observed 1, 48 (2 days), and 24 (1 day) hours after intravitreal administration in the vitreous, aqueous humor, and retina/choroid, respectively. The one-compartment model was selected as the final model for all three ocular tissues. In the vitreous, aqueous humor, and retina/choroid, the estimated half-lives of aflibercept were 94.1, 48.0, and 58.2 hours, and the estimated mean residence times (MRTs) were 135.8, 69.2, and 84.0 hours, respectively. The area under curve from time 0 to the end point (AUClast) was 135,810.6 hours * MUg/mL for the vitreous, 13,889.7 hours * MUg/mL for the aqueous humor, and 2453.1 hours * MUg/g for the retina/choroid. CONCLUSIONS: In rabbits, the vitreous half-life of aflibercept is 94.1 hours (3.92 days). This is shorter than that of bevacizumab (6.99 days), and longer than that of ranibizumab (2.51 days) and VEGF-Trap (3.63 days). PMID- 27258434 TI - Differential Expression of Proteoglycans by Corneal Stromal Cells in Keratoconus. AB - PURPOSE: Keratoconus is a heterogeneous disease associated with a range of pathologies, including disorders that involve proteoglycans (PGs). Some PG alterations, mainly in keratan sulfate (KS), occur in keratoconus. In this article, we studied the differential expression of the genes encoding PGs in cells isolated from keratoconus patients and healthy controls, as well as in corneal sections. METHODS: Human central corneal tissue was obtained from cadaver donors and patients undergoing penetrating keratoplasty surgery. A transcriptomic approach was used, employing quantitative PCR, to analyze both the expression of the enzymes involved in glycosaminoglycan (GAG) biosynthesis and the PG core proteins. The expressions of the differentially expressed core proteins and of the GAG chains were also analyzed by immunocytochemistry in the cultured cells, as well as by immunohistochemistry in corneal sections. RESULTS: The mRNA levels of most major matrix PG mRNAs in the cultured keratoconic stromal cells decreased except collagen XVIII, which increased. At keratocyte surfaces, some heparan sulfate PGs were down-regulated. With respect to GAGs, there were changes in gene expression for the polymerization of the GAG chains, mainly KS and chondroitin sulfate, and in the modification of the saccharidic chains, pointing to an alteration of the sulfation patterns of all GAG species. CONCLUSIONS: Most of the PG core proteins underwent significant changes in cultured keratoconic cells and corneas. With regard to GAG chains, the polymerization of the chains and their chemical modification was modified in way that depended on the specific type of GAG involved. PMID- 27258435 TI - Pigment Epithelial-Derived Factor Peptide Regenerated Limbus Serves as Regeneration Source for Limbal Regeneration in Rabbit Limbal Deficiency. AB - PURPOSE: To demonstrate that a 44-amino acid peptide from pigment epithelial derived factor (PEDF) induces the regeneration of limbal excision wound, and the regenerated limbus can act as the regeneration source for new limbal excisional injuries in rabbit model of limbal deficiency. METHODS: Half circumference partial limbal excision was followed by PEDF peptide treatment to achieve limbal wound regeneration. Three months later, a second stage half circumference partial limbal excision removed the remaining native limbal tissue followed by PEDF peptide treatment. The structure and function of the regenerated limbus were analyzed at 3 and 6 months. Conjunctivalization was analyzed by impression cytology. Immunohistochemical analysis was performed with antibodies to corneal epithelium-associated keratin 3 (K3), conjunctival epithelium-associated keratin 13 (K13), DeltaNp63alpha, ABCG2, and BrdU. Extensive limbal excision was performed to examine the regeneration potential of the PEDF peptide. RESULTS: Total limbal stem cell deficiency occurred with severe inflammation and conjunctivalization of the limbal wound and adjacent cornea in vehicle control eyes. In PEDF peptide treated eyes, the regenerated limbus prevented fibrovascular invasion and goblet cell migration into the corneal surface. Immunohistochemical staining of the regenerated limbus showed a wide distribution of cells expressing DeltaNp63alpha and ABCG2 as in the native limbus. BrdU labeling assay revealed the presence of slow-cycling cells in the basal layer of the regenerated limbus. The PEDF peptide can heal extensive limbal excisional wounds and sustain ocular surface integrity. CONCLUSIONS: The addition of PEDF peptide has the potential to repair limbal excisional wounds with the recovery of normal limbus-like anatomy and function. The PEDF peptide is a potential remedy for extensive limbal injury. PMID- 27258436 TI - Biallelic Mutations in CRB1 Underlie Autosomal Recessive Familial Foveal Retinoschisis. AB - PURPOSE: To identify the genetic cause of autosomal recessive familial foveal retinoschisis (FFR). METHODS: A female sibship with FFR was identified (Family-A; 17 and 16 years, respectively); panel based genetic sequencing (132 genes) and comparative genome hybridization (142 genes) were performed. Whole-exome sequencing (WES) was performed on both siblings using the Illumina-HiSeq-2500 platform. A sporadic male (Family-B; 35 years) with FFR underwent WES using Illumina NextSeq500. All three affected subjects underwent detailed ophthalmologic evaluation including fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinogram (ERG). RESULTS: Panel-based genetic testing identified two presumed disease causing variants in CRB1 (p.Gly123Cys and p.Cys948Tyr) in Family A sibship; no deletion or duplication was detected. WES analysis in the sibship identified nine genes with two or more shared nonsynonymous rare coding sequence variants; CRB1 remained a strong candidate gene, and CRB1 variants segregated with the disease. WES in Family-B identified two presumed disease causing variants in CRB1 (p.Ile167_Gly169del and p.Arg764Cys) that segregated with the disease phenotype. Distance visual acuity was 20/40 or better in all three affected except for the left eye of the older subject (Family-B), which showed macular atrophy. Fundus evaluation showed spoke-wheel appearance at the macula in five eyes. The SD-OCT showed macular schitic changes in inner and outer nuclear layers in all cases. The ERG responses were normal in all subjects. CONCLUSIONS: This is the first report to implicate CRB1 as the underlying cause of FFR. This phenotype forms the mildest end of the spectrum of CRB1-related diseases. PMID- 27258439 TI - Not a Simple Plumbing Problem: Updating Our Understanding of Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage. PMID- 27258437 TI - Prodrugs Bioactivated to Quinones Target NF-kappaB and Multiple Protein Networks: Identification of the Quinonome. AB - Electrophilic reactive intermediates resulting from drug metabolism have been associated with toxicity and off-target effects and in some drug discovery programs trigger NO-GO decisions. Many botanicals and dietary supplements are replete with such reactive electrophiles, notably Michael acceptors, which have been demonstrated to elicit chemopreventive mechanisms; and Michael acceptors are gaining regulatory approval as contemporary cancer therapeutics. Identifying protein targets of these electrophiles is central to understanding potential therapeutic benefit and toxicity risk. NO-donating NSAID prodrugs (NO-NSAIDs) have been the focus of extensive clinical and preclinical studies in inflammation and cancer chemoprevention and therapy: a subset exemplified by pNO-ASA, induces chemopreventive mechanisms following bioactivation to an electrophilic quinone methide (QM) Michael acceptor. Having previously shown that these NO-independent, QM-donors activated Nrf2 via covalent modification of Keap-1, we demonstrate that components of canonical NF-kappaB signaling are also targets, leading to the inhibition of NF-kappaB signaling. Combining bio-orthogonal probes of QM-donor ASA prodrugs with mass spectrometric proteomics and pathway analysis, we proceeded to characterize the quinonome: the protein cellular targets of QM modification by pNO-ASA and its ASA pro-drug congeners. Further comparison was made using a biorthogonal probe of the "bare-bones", Michael acceptor, and clinical anti-inflammatory agent, dimethyl fumarate, which we have shown to inhibit NF-kappaB signaling. Identified quinonome pathways include post translational protein folding, cell-death regulation, protein transport, and glycolysis; and identified proteins included multiple heat shock elements, the latter functionally confirmed by demonstrating activation of heat shock response. PMID- 27258438 TI - The Importance of the Biological Impact of Exposure to the Concept of the Exposome. AB - BACKGROUND: The term "exposome" was originally coined in 2005 and defined as the totality of exposures throughout the lifetime. The exposome provides an excellent scientific framework for studying human health and disease. Recently, it has been suggested that how exposures affect our biology and how our bodies respond to such exposures should be part of the exposome. OBJECTIVES: The authors describe the biological impact of the exposome and outline many of the targets and processes that can be assessed as part of a comprehensive analysis of the exposome. DISCUSSION: The processes that occur downstream from the initial interactions with exogenous and endogenous compounds determine the biological impact of exposures. If the effects are not considered in the same context as the exposures, it will be difficult to determine cause and effect. The exposome and biology are interactive-changes in biology due to the environment change one's vulnerability to subsequent exposures. Additionally, highly resilient individuals are able to withstand environmental exposures with minimal effects to their health. We expect that the vast majority of exposures are transient, and chemicals underlying exposures that occurred weeks, months, or years ago are long gone from the body. However, these past chemical exposures often leave molecular fingerprints that may be able to provide information on these past exposures. CONCLUSIONS: Through linking exposures to specific biological responses, exposome research could serve to improve understanding of the mechanistic connections between exposures and health to help mitigate adverse health outcomes across the lifespan. CITATION: Dennis KK, Auerbach SS, Balshaw DM, Cui Y, Fallin MD, Smith MT, Spira A, Sumner S, Miller GW. 2016. The importance of the biological impact of exposure to the concept of the exposome. Environ Health Perspect 124:1504 1510; http://dx.doi.org/10.1289/EHP140. PMID- 27258440 TI - The Pathophysiology of Delayed Cerebral Ischemia. AB - Subarachnoid hemorrhage (SAH) affects 30,000 people in the Unites States alone each year. Delayed cerebral ischemia occurs days after subarachnoid hemorrhage and represents a potentially treatable cause of morbidity for approximately one third of those who survive the initial hemorrhage. While vasospasm has been traditionally linked to the development of cerebral ischemia several days after subarachnoid hemorrhage, emerging evidence reveals that delayed cerebral ischemia is part of a much more complicated post-subarachnoid hemorrhage syndrome. The development of delayed cerebral ischemia involves early arteriolar vasospasm with microthrombosis, perfusion mismatch and neurovascular uncoupling, spreading depolarizations, and inflammatory responses that begin at the time of the hemorrhage and evolve over time, culminating in cortical infarction. Large-vessel vasospasm is likely a late contributor to ongoing injury, and effective treatment for delayed cerebral ischemia will require improved detection of critical early pathophysiologic changes as well as therapeutic options that target multiple related pathways. PMID- 27258441 TI - Seizures and Epileptiform Patterns in SAH and Their Relation to Outcomes. AB - In subarachnoid hemorrhage (SAH), seizures are frequent and occur at different time points, likely reflecting heterogeneous pathophysiology. Young patients, those with more severe SAH (by clot burden or presence of severe mental status changes at onset or focal neurologic deficits at any time), those with associated increased cortical irritation (by infarction or presence of underlying hematoma), and patients undergoing craniotomy are at higher risk. Advanced neurophysiologic monitoring allows for seizure burden quantification, identification of subclinical seizures, and interictal patterns as well as neurovascular complications that may have an independent impact on the outcome in this population. Practice regarding seizure prophylaxis varies widely; its institution is often guided by the risk-benefit ratio of seizures and medication side effects. Newer anticonvulsants seem to be equally effective and may have a more favorable profile. However, questions regarding the association of seizures and vasospasm, the therapeutic dosing, timing, and duration of antiepileptic treatment and the impact of seizures and antiepileptics on the outcome remain unanswered. In this review, we provide a broad overview of the work in this area and offer a diagnostic and therapeutic approach based on our own expert opinion. PMID- 27258443 TI - EEG Monitoring in Cerebral Ischemia: Basic Concepts and Clinical Applications. AB - EEG is very sensitive to changes in neuronal function resulting from ischemia. The authors briefly review essentials of EEG generation and the effects of ischemia on the underlying neuronal processes. They discuss the differential sensitivity of various neuronal processes to energy limitations, including synaptic disturbances. The clinical applications reviewed include continuous EEG monitoring during carotid surgery and acute ischemic stroke, and EEG monitoring for prognostication after cardiac arrest. PMID- 27258442 TI - Spreading Depolarizations: A Therapeutic Target Against Delayed Cerebral Ischemia After Subarachnoid Hemorrhage. AB - Delayed cerebral ischemia is the most feared cause of secondary injury progression after subarachnoid hemorrhage. Initially thought to be a direct consequence of large artery spasm and territorial ischemia, recent data suggests that delayed cerebral ischemia represents multiple concurrent and synergistic mechanisms, including microcirculatory dysfunction, inflammation, and microthrombosis. Among these mechanisms, spreading depolarizations (SDs) are arguably the most elusive and underappreciated in the clinical setting. Although SDs have been experimentally detected and examined since the late 1970s, their widespread occurrence in human brain was not unequivocally demonstrated until relatively recently. We now know that SDs occur with very high incidence in human brain after ischemic or hemorrhagic stroke and trauma, and worsen outcomes by increasing metabolic demand, decreasing blood supply, predisposing to seizure activity, and possibly worsening brain edema. In this review, we discuss the causes and consequences of SDs in injured brain. Although much of our mechanistic knowledge comes from experimental models of focal cerebral ischemia, clinical data suggest that the same principles apply regardless of the mode of injury (i.e., ischemia, hemorrhage, or trauma). The hope is that a better fundamental understanding of SDs will lead to novel therapeutic interventions to prevent SD occurrence and its adverse consequences contributing to injury progression in subarachnoid hemorrhage and other forms of acute brain injury. PMID- 27258444 TI - Current Clinical Evidence Supporting the Use of Continuous EEG Monitoring for Delayed Cerebral Ischemia Detection. AB - The EEG signal is the closest available measure of brain function and is exquisitely sensitive to ischemia. Data from animal models and from intraoperative monitoring suggest that continuous EEG monitoring is able disclose changes suggestive of impeding ischemia before infarction occurs. Several small studies in patients with aneurysmal subarachnoid hemorrhage now provide preliminary evidence that it can also be successfully applied to detection of delayed cerebral ischemia with a good sensitivity. These studies relied on quantitative analysis, underscoring the necessity to introduce such methods in clinical practice. Further improvements in quantitative EEG analysis, integration in a multimodality monitoring framework, and prospective validation studies are now required to confirm the utility of EEG monitoring for delayed cerebral ischemia detection. PMID- 27258445 TI - Clinical Development and Implementation of an Institutional Guideline for Prospective EEG Monitoring and Reporting of Delayed Cerebral Ischemia. AB - Delayed cerebral ischemia (DCI) is the most common and disabling complication among patients admitted to the hospital for subarachnoid hemorrhage (SAH). Clinical and radiographic methods often fail to detect DCI early enough to avert irreversible injury. We assessed the clinical feasibility of implementing a continuous EEG (cEEG) ischemia monitoring service for early DCI detection as part of an institutional guideline. An institutional neuromonitoring guideline was designed by an interdisciplinary team of neurocritical care, clinical neurophysiology, and neurosurgery physicians and nursing staff and cEEG technologists. The interdisciplinary team focused on (1) selection criteria of high-risk patients, (2) minimization of safety concerns related to prolonged monitoring, (3) technical selection of quantitative and qualitative neurophysiologic parameters based on expert consensus and review of the literature, (4) a structured interpretation and reporting methodology, prompting direct patient evaluation and iterative neurocritical care, and (5) a two-layered quality assurance process including structured clinician interviews assessing events of neurologic worsening and an adjudicated consensus review of neuroimaging and medical records. The resulting guideline's clinical feasibility was then prospectively evaluated. The institutional SAH monitoring guideline used transcranial Doppler ultrasound and cEEG monitoring for vasospasm and ischemia monitoring in patients with either Fisher group 3 or Hunt-Hess grade IV or V SAH. Safety criteria focused on prevention of skin breakdown and agitation. Technical components included monitoring of transcranial Doppler ultrasound velocities and cEEG features, including quantitative alpha:delta ratio and percent alpha variability, qualitative evidence of new focal slowing, late-onset epileptiform activity, or overall worsening of background. Structured cEEG reports were introduced including verbal communication for findings concerning neurologic decline. The guideline was successfully implemented over 27 months, during which neurocritical care physicians referred 71 SAH patients for combined transcranial Doppler ultrasound and cEEG monitoring. The quality assurance process determined a DCI rate of 48% among the monitored population, more than 90% of which occurred during the duration of cEEG monitoring (mean 6.9 days) beginning 2.7 days after symptom onset. An institutional guideline implementing cEEG for SAH ischemia monitoring and reporting is feasible to implement and efficiently identify patients at high baseline risk of DCI during the period of monitoring. PMID- 27258446 TI - Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do. AB - The purpose of this study is to evaluate automated implementations of continuous EEG monitoring-based detection of delayed cerebral ischemia based on methods used in classical retrospective studies. We studied 95 patients with either Fisher 3 or Hunt Hess 4 to 5 aneurysmal subarachnoid hemorrhage who were admitted to the Neurosciences ICU and underwent continuous EEG monitoring. We implemented several variations of two classical algorithms for automated detection of delayed cerebral ischemia based on decreases in alpha-delta ratio and relative alpha variability. Of 95 patients, 43 (45%) developed delayed cerebral ischemia. Our automated implementation of the classical alpha-delta ratio-based trending method resulted in a sensitivity and specificity (Se,Sp) of (80,27)%, compared with the values of (100,76)% reported in the classic study using similar methods in a nonautomated fashion. Our automated implementation of the classical relative alpha variability-based trending method yielded (Se,Sp) values of (65,43)%, compared with (100,46)% reported in the classic study using nonautomated analysis. Our findings suggest that improved methods to detect decreases in alpha delta ratio and relative alpha variability are needed before an automated EEG based early delayed cerebral ischemia detection system is ready for clinical use. PMID- 27258447 TI - Interrater Agreement for Consensus Definitions of Delayed Ischemic Events After Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Thirty percent of patients with subarachnoid hemorrhage experience delayed cerebral ischemia or delayed ischemic neurologic decline (DIND). Variability in the definitions of delayed ischemia makes outcome studies difficult to compare. A recent consensus statement advocates standardized definitions for delayed ischemia in clinical trials of subarachnoid hemorrhage. We sought to evaluate the interrater agreement of these definitions. METHODS: Based on consensus definitions, we assessed for: (1) delayed cerebral infarction, defined as radiographic cerebral infarction; (2) DIND type 1 (DIND1), defined as focal neurologic decline; and (3) DIND2, defined as a global decline in arousal. Five neurologists retrospectively reviewed electronic records of 58 patients with subarachnoid hemorrhage. Three reviewers had access to and reviewed neuroradiology imaging. We assessed interrater agreement using the Gwet kappa statistic. RESULTS: Interrater agreement statistics were excellent (95.83%) for overall agreement on the presence or absence of any delayed ischemic event (DIND1, DIND2, or delayed cerebral infarction). Agreement was "moderate" for specifically identifying DIND1 (56.58%) and DIND2 (48.66%) events. We observed greater agreement for DIND1 when there was a significant focal motor decline of at least 1 point in the motor score. There was fair agreement (39.20%) for identifying delayed cerebral infarction; CT imaging was the predominant modality. CONCLUSIONS: Consensus definitions for delayed cerebral ischemia yielded near perfect overall agreement and can thus be applied in future large-scale studies. However, a strict process of adjudication, explicit thresholds for determining focal neurologic decline, and MRI techniques that better discriminate edema from infarction seem critical for reproducibility of determination of specific outcome phenotypes, and will be important for successful clinical trials. PMID- 27258448 TI - Intracranial Multimodality Monitoring for Delayed Cerebral Ischemia. AB - Management of patients with aneurysmal subarachnoid hemorrhage focuses on prevention of rebleeding by early treatment of the aneurysm, as well as detection and management of neurologic and medical complications. Early detection of delayed cerebral ischemia and management of modifiable contributing causes such as vasospasm take a central role, with the goal of preventing irreversible cerebral injury. In efforts to prevent delayed cerebral ischemia, multimodality monitoring has emerged as a promising tool in detecting subclinical physiologic changes before infarction occurs. However, there has been much variability in the utilization of this technology. Recent consensus guidelines discuss the role of multimodality monitoring in acute brain injury. In this review, we evaluate these guidelines and the utility of each modality of multimodality monitoring in aneurysmal subarachnoid hemorrhage. PMID- 27258449 TI - Complications in Aneurysmal Subarachnoid Hemorrhage Patients With and Without Subdural Electrode Strip for Electrocorticography. AB - PURPOSE: Patients with aneurysmal subarachnoid hemorrhage (aSAH) frequently develop secondary noninfectious and infectious complications with an important impact on clinical course and outcome. In this study, we report on the rate of typical extracranial and intracranial complications in 30 prospectively enrolled patients with severe aSAH who received a linear subdural recording strip for continuous electrocorticography to detect ictal epileptiform events and spreading depolarizations. METHODS: The group was compared with 30 retrospectively included patients with aSAH who had not received a subdural recording strip, but were treated during the same period. The control group was matched according to an aSAH grading system, sex, and establishment of external ventricular drainage, but could not be matched according to aneurysm treatment and focal brain lesions such as initial intracerebral hemorrhages. RESULTS: No evidence was found that procedures of the electrocorticography study led to clinically relevant complications. In particular, the subdural strip did not lead to local damage of brain tissue or any increased rate of meningitis/ventriculitis. The median score on the modified Rankin Scale on day 15 was the same in both groups. Minor differences between both groups are explained by the limitations in the study design. CONCLUSIONS: Our study suggests that neuromonitoring with a subdural recording strip for up to 15 days can be safely performed in patients with aSAH. PMID- 27258450 TI - Noninvasive Vascular Methods for Detection of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage. AB - The development of delayed cerebral ischemia after subarachnoid hemorrhage is one of the most important determinants of poor neurologic outcome. The pathophysiology of delayed cerebral ischemia relies on a complex interplay between a significant reduction of the diameter of large intracranial arteries (vasospasm), microvascular disturbances, and spreading cortical depolarization that lead to an inadequate oxygen supply to the brain parenchyma. The early diagnosis of cerebral vasospasm is a real challenge for clinicians and requires a multimodal approach to evaluate the consequences of vascular narrowing on cerebral function. Considering the costs and limited availability of invasive techniques, noninvasive tools may provide continuous and reliable information to detect vasospasm in patients with subarachnoid hemorrhage. In this article, we review in particular the role of transcranial Doppler ultrasonography, cerebral near-infrared spectroscopy, and brain imaging to detect cerebral vasospasm and delayed cerebral ischemia in this patients' population. PMID- 27258451 TI - Heart Rate Variability for the Early Detection of Delayed Cerebral Ischemia. AB - Delayed cerebral ischemia is considered the leading cause of death or major disability in subarachnoid hemorrhage after the impact of the initial event and rebleeding. Waiting to treat patients until they exhibit clinical symptoms of ischemia is too late to prevent cerebral infarction for more than 60% of patients, and transcranial Doppler ultrasonography has not proven to be a reliable screening tool to identify high-risk patients. Continuous heart rate variability monitoring may provide an alternative screening strategy to identify patients at high risk for delayed cerebral ischemia. Heart rate variability is a composite reflection of autonomic outflow, neuroendocrine influences, and autonomic responsiveness. Most importantly, heart rate variability is responsive to changes in systemic inflammation, which evidence suggests is important to the causal pathway of delayed cerebral ischemia. The clinical application of continuous heart rate variability monitoring in critical care is relatively recent despite its existence for more than 50 years. Initial studies suggest promise for heart rate variability monitoring as a delayed cerebral ischemia screening tool, but significant research is still required before this approach may achieve clinical applicability and bring benefit to patients. PMID- 27258452 TI - Biological Control of Meloidogyne incognita by Aspergillus niger F22 Producing Oxalic Acid. AB - Restricted usage of chemical nematicides has led to development of environmentally safe alternatives. A culture filtrate of Aspergillus niger F22 was highly active against Meloidogyne incognita with marked mortality of second stage juveniles (J2s) and inhibition of egg hatching. The nematicidal component was identified as oxalic acid by organic acid analysis and gas chromatography mass spectroscopy (GC-MS). Exposure to 2 mmol/L oxalic acid resulted in 100% juvenile mortality at 1 day after treatment and suppressed egg hatching by 95.6% at 7 days after treatment. Oxalic acid showed similar nematicidal activity against M. hapla, but was not highly toxic to Bursaphelenchus xylophilus. The fungus was incubated on solid medium and dried culture was used for preparation of a wettable powder-type (WP) formulation as an active ingredient. Two WP formulations, F22-WP10 (ai 10%) and oxalic acid-WP8 (ai 8%), were prepared using F22 solid culture and oxalic acid. In a field naturally infested with M. incognita, application of a mixture of F22-WP10 + oxalic acid-WP8 at 1,000- and 500-fold dilutions significantly reduced gall formation on the roots of watermelon plants by 58.8 and 70.7%, respectively, compared to the non-treated control. The disease control efficacy of the mixture of F22-WP10 + oxalic acid WP8 was significantly higher than that of a chemical nematicide, Sunchungtan (ai 30% fosthiazate). These results suggest that A. niger F22 can be used as a microbial nematicide for the control of root-knot nematode disease. PMID- 27258454 TI - Patient With Nasal Obstruction. PMID- 27258455 TI - Subconcussive Head Trauma and Near Point of Convergence. PMID- 27258457 TI - INVEST IN YOURSELF, INSPIRE OTHERS, JAZZ UP YOUR JOURNEY. PMID- 27258456 TI - Relationship Between Glucocorticoids and Insulin Resistance in Healthy Individuals. AB - BACKGROUND The aim of this study was to determine the correlation between glucocorticoids (GCs) and insulin resistance (IR) in healthy individuals by conducting a systematic meta-analysis. MATERIAL AND METHODS A systematic literature review was conducted using 9 electronic databases. Only case-control studies investigating fasting plasma glucose (FPG) and IR were enrolled based on strictly established selection criteria. Statistical analyses were performed by Stata software, version 12.0 (Stata Corporation, College Station, Texas, USA). RESULTS Among 496 initially retrieved articles, only 6 papers published in English were eventually included in this meta-analysis. A total of 201 healthy individuals (105 in GC group and 96 in control group) were included in the 6 studies. In 4 of these 6 studies, dexamethasone was used, and in the other 2 studies prednisolone was given. This meta-analysis revealed that the FPG, fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) levels in the GC group were all significantly higher than that in the control group (FPG: SMD=2.65, 95%CI=1.42~3.88, P<0.001; FINS: SMD=2.48, 95%CI=1.01~3.95, P=0.001; HOMA-IR: SMD=38.30, 95%CI=24.38~52.22, P<0.001). CONCLUSIONS In conclusion, our present study revealed that therapies using GCs might result in elevated FPG, FINS, and HOMA-IR, and thereby contribute to IR in healthy individuals. PMID- 27258458 TI - Changing Practice in Gastrointestinal Endoscopy: Reducing Distractions for Patient Safety. AB - Failure in communication during the process of delivering healthcare can have dangerous repercussions. Specifically, failure in interdisciplinary team communication contributes to lapses in patient care. Distractions in procedural areas disrupt team communication. Application of a structured communication algorithm creates agreed-upon cues that promote team communication and facilitate clinical decision making. Frequent disruptions before, during, and after gastro intestinal endoscopy procedures place veterans at risk for an error. A hierarchical culture promotes intimidation and reduces the likelihood that staff will speak up for patient safety. An endoscopy procedure area implemented a "sterile cockpit" methodology to reduce the number of distractions during procedures. Data collected from a self-reported safety awareness were measured by two different questionnaires and collected through observation of actual practice. Improved awareness of distraction and the impact on patient safety was reported, with a reduction from 24 observed interruptions to zero in 9 months. After reducing distractions in the procedural area, there is a perception of improved nursing quality of care. Additional support is required to consistently remove electronic distractions during a procedure. PMID- 27258459 TI - Managing Celiac Disease for Women: Implications for the Primary Care Provider. AB - Although many people have symptoms of celiac disease, it can take a while to diagnose. Villous atrophy may be present long before any gastrointestinal symptoms. An important point to acknowledge is that celiac disease could be identified earlier in some women with a positive family history. The disease also could be the cause of some women's reproductive problems. Primary care providers, using comprehensive history taking, are in the unique position to identify individuals who may have celiac disease, assist women in gaining knowledge about a gluten-free diet, order diagnostic testing, and refer to a gastroenterologist. The positive change in fertility with a simultaneous improvement of nutrient deficiencies shortly after adopting a gluten-free diet indicates a possible link between such nutrients and sex hormone function. High levels of homocysteine, which can negatively impact fertility, have also been linked to individuals with problems, such as celiac disease, that decrease vitamin B12 absorption. The purpose of this article is to review the literature and the evidence-based care guidelines for comprehensive screening, diagnostics, and pathophysiology of celiac disease, with a specific focus on the female reproductive system, anemia management, and gluten-free diet integration. PMID- 27258460 TI - Constipation: Prevalence and Associated Factors in Adults Living in Londrina, Southern Brazil. AB - The aims of this study were to estimate the prevalence of constipation and identify associated factors among adults living in an urban area in Londrina, Brazil. This was a secondary analysis of an epidemiological, population-based study on bowel habit performed in 2008 with 2,162 individuals selected through cluster sampling. Interviews were administered using a sociodemographic questionnaire and the adapted and validated Brazilian version of the "Bowel Function in the Community" tool. Variables from the original database were used to determine the prevalence of constipation (according to the Rome Criteria III) and associated factors. The chi-square test and multivariate logistic regression were used for data analysis. The overall prevalence of constipation (14.6%; n = 315) was higher among women than among men (21.9% vs. 5.3%), increased with age among men, and was inversely related to family income. Overall, female gender, low socioeconomic status, history of anal fissure, anorectal surgery, stroke, nervous system disease, fistulae, and hemorrhoids were factors significantly associated with constipation. The variables low social economic status, stroke, anal fissure history, and anorectal surgery were statistically significant in all three tested statistical models. PMID- 27258461 TI - Colonoscopy Comfort: An Evidence-Based Practice Project. AB - Decreased discomfort after colonoscopy is a high priority for patients. Typically, air is used to insufflate the bowel during colonoscopy, but emerging literature shows that carbon dioxide insufflation decreases postoperative discomfort and flatus. An evidence-based practice project was developed and implemented by a surgical department at a community hospital. The Director of Surgical Services brought the evidence to the staff, secured agreement from a physician champion, and the new process was quickly adopted. Patients experienced less discomfort and flatus postprocedure with carbon dioxide insufflation, and were able to be discharged expediently. These patient outcomes validated the literature and confirmed the success of the practice change. PMID- 27258462 TI - Stigma in Cirrhotic Patients: A Qualitative Study. AB - Stigma is one of the main problems of patients suffering from cirrhosis, and it causes many challenges for the patients and their treatment. The present study aimed to discover and define the perceived stigma by cirrhotic patients. This qualitative study was conducted through a content analysis approach. The participants were 15 patients suffering from cirrhosis. Data were collected via semistructured, in-depth interviews and analyzed on the basis of methods described by Granheme and Landman. During data analysis, stigma was categorized into four categories and 13 subcategories: external representation of social stigma (others' avoidance behaviors, inadmissible tag, discriminative behaviors of treatment personnel, blaming behaviors), internal representation of social stigma (social ostracism, social isolation, curiosity to perceive people's perceptions), external representation of self-stigma (fear of disclosure of illness, threatening situation, difficult emotional relationships), and internal representation of self-stigma (condemned to suffer, self-punishment, self alienation). Experiencing stigma is common among cirrhotic patients and may affect patients' coping with the illness and treatment. Thus, it is specifically important that treatment personnel know patients' perception, provide comprehensive support for these patients, and plan to enhance public awareness about the disease recommended. PMID- 27258463 TI - Frequency of Irritable Bowel Syndrome Among Healthcare Personnel. AB - This study aims to investigate the frequency of irritable bowel syndrome (IBS) among healthcare professionals. A total of 394 healthcare professionals and 207 individuals who were selected as a control group were included in the study. A questionnaire form containing Rome III diagnostic criteria was administered to health workers and the control group. The study groups were evaluated according to age, gender, occupation, profession, presence of chronic disease, drug usage, smoking, awareness of IBS, alarm symptoms, and the type of IBS they have. Irritable bowel syndrome was diagnosed in 44 healthcare workers and 10 control group participants. Of the 44 healthcare professionals with IBS, 6 had alternate, 13 had constipated-dominant, and 25 had diarrhea-dominant IBS. Of the 10 persons in the control group who were diagnosed as having IBS, 5 were diarrhea-dominant and 5 were constipated-dominant type. Irritable bowel syndrome was more frequent in healthcare professionals than in the control group. Healthcare workers are more prone to IBS due to their stressful working environment. PMID- 27258464 TI - MANAGEMENT OF ACUTE CARDIAC TAMPONADE AFTER ESOPHAGEAL PERFORATION BY A STEEL WIRE. PMID- 27258465 TI - CROHN DISEASE PRESENTED WITH A GIANT COLONIC MASS. PMID- 27258466 TI - PYODERMA GANGRENOSUM AS AN INITIAL PRESENTING SYMPTOM OF SILENT ULCERATIVE COLITIS. PMID- 27258467 TI - ARE THERE CRITICAL USES OF GLOVES IN TERMS OF SELF-PROTECTION? PMID- 27258468 TI - "A VISCERAL RESPONSE": My Personal Poetry. PMID- 27258469 TI - CAN ADJUVANT AGENTS REDUCE GASTRIC ACIDITY IN PATIENTS WITH CYSTIC FIBROSIS: EVIDENCE FROM A COCHRANE REVIEW. PMID- 27258470 TI - Stimulants and Pediatric Cardiovascular Risk. AB - OBJECTIVE: Concerns about serious cardiovascular (CV) events among stimulant treated youth have led to clinical and policy debates. Accordingly, several population-based empirical studies have assessed the risk of CV events in children and adolescents treated with stimulants. The main objective of this review was to summarize findings and to evaluate the strengths and weaknesses of these population-based studies. In addition, we discuss the CV monitoring and policy implications for a clinically focused audience. METHODS: A computerized literature search of Medline and PsycINFO was conducted for the calendar years 1990-2015 to identify population-based studies assessing stimulant treatment emergent CV events in youth. Additional reports, peer-reviewed or gray literature, for example, government reports, were also included. RESULTS: Nine population-based studies (one case-control and eight retrospective cohort designs) were included in this review. The case-control study compared sudden unexplained death cases to age-matched controls (motor vehicle passenger deaths) with respect to prior stimulant use and found a significant association (odds ratio = 7.4 [95% CI: 1.4-74.9]). By contrast, most retrospective cohort studies assessed the risk of serious CV events (i.e., sudden death, myocardial infarction, and stroke) and did not find an association with current stimulant exposure. The absolute rate for these serious events was low, but other data support risk. For example, cardiac-related emergency department visits showed a 20% increased risk for current stimulant users compared with nonusers in one study, and another study showed a 64% and 90% increased risk for concurrent use of stimulants with antidepressants and antipsychotics, respectively. Similarly, in another study, compared with nonusers, stimulant users had twofold greater odds of CV-related inpatient or outpatient services. CONCLUSION: In the face of mixed results from population-based safety studies, this review supports the inclusion of baseline and ongoing monitoring of cardiac status to assure a favorable benefit risk profile for stimulant users, particularly in concomitant regimens with antipsychotics and antidepressants. PMID- 27258471 TI - Wheat PR-1 proteins are targeted by necrotrophic pathogen effector proteins. AB - Recent studies have identified that proteinaceous effectors secreted by Parastagonospora nodorum are required to cause disease on wheat. These effectors interact in a gene-for-gene manner with host-dominant susceptibilty loci, resulting in disease. However, whilst the requirement of these effectors for infection is clear, their mechanisms of action remain poorly understood. A yeast two-hybrid library approach was used to search for wheat proteins that interacted with the necrotrophic effector SnTox3. Using this strategy we indentified an interaction between SnTox3 and the wheat pathogenicity-related protein TaPR-1-1, and confirmed it by in-planta co-immunprecipitation. PR-1 proteins represent a large family (23 in wheat) of proteins that are upregulated early in the defence response; however, their function remains ellusive. Interestingly, the P. nodorum effector SnToxA has recently been shown to interact specifically with TaPR-1-5. Our analysis of the SnTox3-TaPR-1 interaction demonstrated that SnTox3 can interact with a broader range of TaPR-1 proteins. Based on these data we utilised homology modeling to predict, and validate, regions on TaPR-1 proteins that are likely to be involved in the SnTox3 interaction. Precipitating from this work, we identified that a PR-1-derived defence signalling peptide from the C-terminus of TaPR-1-1, known as CAPE1, enhanced the infection of wheat by P. nodorum in an SnTox3-dependent manner, but played no role in ToxA-mediated disease. Collectively, our data suggest that P. nodorum has evolved unique effectors that target a common host-protein involved in host defence, albeit with different mechanisms and potentially outcomes. PMID- 27258473 TI - Noncovalent inhibitors of human 20S and 26S proteasome based on trypsin inhibitor SFTI-1. AB - Sunflower trypsin inhibitor (SFTI-1) is recognized as an attractive scaffold to designed potent inhibitors of various proteases. We have recently found that its analogues inhibit noncovalently both human and yeast 20S proteasomes. Here, a set of novel and more potent in vitro inhibitors is presented. The inhibitory potency of the peptides was assessed with human 20S proteasome in the presence or absence of sodium dodecyl sulfate and with human 26 proteasome. Their antiproliferative action against tumor (human melanoma cells A375) and normal cells (46 BR.1N human fibroblasts and HaCaT keratinocytes) was determined. The selected fluoresceine labeled inhibitors were able to internalize into A375 cells and were sometimes present as foci in the cells. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 685-696, 2016. PMID- 27258472 TI - Irradiated human endothelial progenitor cells induce bystander killing in human non-small cell lung and pancreatic cancer cells. AB - Purpose To investigate whether irradiated human endothelial progenitor cells (hEPC) could induce bystander killing in the A549 non-small cell lung cancer (NSCLC) cells and help explain the improved radiation-induced tumor cures observed in A549 tumor xenografts co-injected with hEPC. Materials and methods We investigated whether co-injection of CBM3 hEPC with A549 NSCLC cells would alter tumor xenograft growth rate or tumor cure after a single dose of 0 or 5 Gy of X rays. We then utilized dual chamber Transwell dishes, to test whether medium from irradiated CBM3 and CBM4 hEPC would induce bystander cell killing in A549 cells, and as an additional control, in human pancreatic cancer MIA PaCa-2 cells. The CBM3 and CBM4 hEPC were plated into the upper Transwell chamber and the A549 or MIA PaCa-2 cells were plated in the lower Transwell chamber. The top inserts with the CBM3 or CBM4 hEPC cells were subsequently removed, irradiated, and then placed back into the Transwell dish for 3 h to allow for diffusion of any potential bystander factors from the irradiated hEPC in the upper chamber through the permeable membrane to the unirradiated cancer cells in the lower chamber. After the 3 h incubation, the cancer cells were re-plated for clonogenic survival. Results We found that co-injection of CBM3 hEPC with A549 NSCLC cells significantly increased the tumor growth rate compared to A549 cells alone, but paradoxically also increased A549 tumor cure after a single dose of 5 Gy of X rays (p < 0.05). We hypothesized that irradiated hEPC may be inducing bystander killing in the A549 NSCLC cells in tumor xenografts, thus improving tumor cure. Bystander studies clearly showed that exposure to the medium from irradiated CBM3 and CBM4 hEPC induced significant bystander killing and decreased the surviving fraction of A549 and MIA PaCa-2 cells to 0.46 (46%) +/- 0.22 and 0.74 +/- 0.07 (74%) respectively (p < 0.005, p < 0.0001). In addition, antibody depletion studies demonstrated that the bystander killing induced in both A549 and MIA PaCa 2 cells was mediated by the cytokines TNF-alpha and TGF-beta (p < 0.05). Conclusions These data provide evidence that irradiated hEPC can induce strong bystander killing in A549 and MIA PaCa-2 human cancer cells and that this bystander killing is mediated by the cytokines TNF-alpha and TGF-beta. PMID- 27258474 TI - Porous Mn2 O3 : A Low-Cost Electrocatalyst for Oxygen Reduction Reaction in Alkaline Media with Comparable Activity to Pt/C. AB - Preparing nonprecious metal catalysts with high activity in the oxygen reduction reaction (ORR) can promote the development of energy conversion devices. Support free porous Mn2 O3 was synthesized by a facile aerosol-spray-assisted approach (ASAA) and subsequent thermal treatment, and exhibited ORR activity that is comparable to commercial Pt/C The catalyst also exhibits notably higher activity than other Mn-based oxides, such as Mn3 O4 and MnO2 . The rotating ring disk electrode (RRDE) study indicates a typical 4-electron ORR pathway on Mn2 O3 . Furthermore, the porous Mn2 O3 demonstrates considerable stability and a good methanol tolerance in alkaline media. In light of the low cost and high earth abundance of Mn, the highly active Mn2 O3 is a promising candidate to be used as a cathode material in metal-air batteries and alkaline fuel cells. PMID- 27258475 TI - Understanding and Exploitation of Neighboring Heteroatom Effect for the Mild N Arylation of Heterocycles with Diaryliodonium Salts under Aqueous Conditions: A Theoretical and Experimental Mechanistic Study. AB - The mechanism of arylation of N-heterocycles with unsymmetric diaryliodonium salts is elucidated. The fast and efficient N-arylation reaction is interpreted in terms of the bifunctionality of the substrate: The consecutive actions of properly oriented Lewis base and Bronsted acid centers in sufficient proximity result in the fast and efficient N-arylation. The mechanistic picture points to a promising synthetic strategy where suitably positioned nucleophilic and acidic centers enable functionalization, and it is tested experimentally. PMID- 27258476 TI - Four-year results of a prospective single-arm study on 200 semi-constrained total cervical disc prostheses: clinical and radiographic outcome. AB - OBJECTIVE Recent studies have described encouraging outcomes after cervical total disc replacement (cTDR), but there are also critical debates regarding the long term effects of heterotopic ossification (HO) and the prevalence of adjacent level degeneration. The aim in this paper was to provide 4-year clinical and radiographic outcome results on the activ C disc prosthesis. METHODS A total of 200 subjects underwent single-level activ C (Aesculap AG) implantation between C 3 and C-7 for the treatment of symptomatic degenerative disc disease. Clinical and radiographic assessments were performed preoperatively, intraoperatively, at discharge, and again at 6 weeks, 6 months, 1 year, 2 years, and 4 years. Radiographic evaluations were done by an independent core laboratory using a specific software for quantitative motion analysis. RESULTS Neck Disability Index (NDI) and visual analog scale (VAS) score for neck and arm pain decreased significantly from baseline to the 4-year follow-up. The mean improvement for NDI was 20, for VAS severity and frequency of neck pain 26.4 and 28, and for VAS severity and frequency of arm pain 30.7 and 35.1, respectively. The neurological situation improved for the majority of patients (86.4%); 76.1% of cases were asymptomatic. Subsequent surgical interventions were reported in 7% of the cases, including device removals in 3%. In 2.5% a subsidence greater than 3 mm was recorded; 1 of these cases also had a migration greater than 3 mm. No device displacement, expulsion, disassembly, loose or fractured device, osteolysis, or facet joint degeneration at the index level was observed. Segmental lordotic alignment changed from -2.4 degrees preoperatively to -6.2 degrees at 4 years, and postoperative height was maintained during the follow-up. Advanced HO (Grade III and IV) was present in 27.1% of the cases; 82.4% showed segmental mobility. A progression of radiographic adjacent-segment degeneration occurred in 28.2%, but only 4.5% required surgical treatment. CONCLUSIONS The activ C is a safe and effective device for cervical disc replacement confirming the encouraging results after cTDR. Clinical trial registration no.: NCT02492724 ( clinicaltrials.gov ). PMID- 27258477 TI - Posterior reversible encephalopathy syndrome following a thoracic discectomy induced dural leak: case report. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterized by headaches, altered mental status, seizures, and visual disturbances. Classic MRI findings include white matter changes of the parieto occipital regions. This syndrome has been encountered in myriad medical illnesses, including hypertension, preeclampsia/eclampsia, and immunosuppressive conditions. While the pathogenesis of the disorder is unclear, vasoconstriction and hypoperfusion leading to brain ischemia and vasogenic edema have been implicated as potential mechanisms. The authors present, to the best of their knowledge, the first case of PRES following a thoracic spinal surgery-induced dural leak noted on resection of the fifth rib during a thoracotomy for a T4-5 discectomy. Brain MRI revealed large areas of increased FLAIR and T2 hyperintensity in the superior posterior frontal lobes, superior and medial parietal lobes, and bilateral occipital lobes. Following repair of the CSF leak, the patient's symptoms resolved. Spinal surgeons should be alert to the potentially life-threatening condition of PRES, especially in a hypertensive patient who experiences surgery-induced dural leakage. The development of a severe positional headache with neurological signs is a red flag that suggests the presence of PRES. Prompt attention to the diagnosis and treatment of this condition by repairing the dural leak via surgery or expeditious blood patch increases the likelihood of a favorable outcome. PMID- 27258478 TI - The effect of vancomycin powder on human dural fibroblast culture and its implications for dural repair during spine surgery. AB - OBJECTIVE Surgical site infections (SSIs) are a major source of morbidity after spinal surgery. Several recent studies have described the finding that applying vancomycin powder to the surgical bed may reduce the incidence of SSI. However, applying vancomycin in high concentrations has been shown in vitro to inhibit osteoblast proliferation and to induce cell death. Vancomycin may have a deleterious effect on dural healing after repair of an intentional or unintentional durotomy. This study was therefore undertaken to assess the effect of different concentrations of vancomycin on a human dura mater cell culture. METHODS Human dura intended for disposal after decompressive craniectomy was harvested. Explant primary cultures and subcultures were subsequently performed. Cells were characterized through common staining and immunohistochemistry. A growth curve was performed to assess the effect of different concentrations of vancomycin (40, 400, and 4000 MUg/ml) on cell count. The effect of vancomycin on cellular shape, intercellular arrangement, and viability was also evaluated. RESULTS All dural tissue samples successfully developed into fusiform cells, demonstrating pseudopod projections and spindle formation. The cells demonstrated vimentin positivity and also had typical features of fibroblasts. When applied to the cultures, the highest dose of vancomycin induced generalized cell death within 24 hours. The mean (+/- SD) cell counts for control, 40, 400, and 4000 MUg/ml were 38.72 +/- 15.93, 36.28 +/- 22.87, 19.48 +/- 6.53, and 4.07 +/- 9.66, respectively (p < 0.0001, ANOVA). Compared with controls, vancomycin-exposed cells histologically demonstrated a smaller cytoplasm and decreased pseudopodia formation resulting in the inhibition of normal spindle intercellular arrangement. CONCLUSIONS When vancomycin powder is applied locally, dural cells are exposed to a concentration several times greater than when delivered systemically. In this in vitro model, vancomycin induced dural cell death, inhibited growth, and altered cellular morphology in a concentration-dependent fashion. Defining a safe vancomycin concentration that is both bactericidal and also does not inhibit normal dural healing is necessary. PMID- 27258479 TI - Letter to the Editor: Rotational thromboelastometry-guided transfusion. PMID- 27258480 TI - Tropheryma whipplei infection (Whipple's disease) in a patient after liver transplantation. AB - Whipple's disease (WD) is a rare infection caused by the bacterium Tropheryma whipplei that can affect multiple organs and most commonly occurs in the immunocompetent host. Only 3 cases of WD have been reported in the setting of immunosuppression for organ transplantation. Here, we report the first case of WD, to our knowledge, in a patient after liver transplantation with comorbid graft-versus-host-disease. We discuss the diagnostic challenges in this setting and the value of electron microscopy and in situ hybridization methods for confirming the infection. WD may be under-diagnosed in immunosuppressed transplant patients because the disease can present with atypical clinical and histological features that suggest other conditions. PMID- 27258481 TI - High-throughput estimation of incident light, light interception and radiation use efficiency of thousands of plants in a phenotyping platform. AB - Light interception and radiation-use efficiency (RUE) are essential components of plant performance. Their genetic dissections require novel high-throughput phenotyping methods. We have developed a suite of methods to evaluate the spatial distribution of incident light, as experienced by hundreds of plants in a glasshouse, by simulating sunbeam trajectories through glasshouse structures every day of the year; the amount of light intercepted by maize (Zea mays) plants via a functional-structural model using three-dimensional (3D) reconstructions of each plant placed in a virtual scene reproducing the canopy in the glasshouse; and RUE, as the ratio of plant biomass to intercepted light. The spatial variation of direct and diffuse incident light in the glasshouse (up to 24%) was correctly predicted at the single-plant scale. Light interception largely varied between maize lines that differed in leaf angles (nearly stable between experiments) and area (highly variable between experiments). Estimated RUEs varied between maize lines, but were similar in two experiments with contrasting incident light. They closely correlated with measured gas exchanges. The methods proposed here identified reproducible traits that might be used in further field studies, thereby opening up the way for large-scale genetic analyses of the components of plant performance. PMID- 27258482 TI - Janus "nano-bullets" for magnetic targeting liver cancer chemotherapy. AB - Tumor-targeted delivery of anti-cancer drugs with controlled drug release function has been recognized as a promising strategy for pursuit of increased chemotherapeutic efficacy and reduced adverse effects. Development of magnetic nanoparticulates as delivery carriers to accommodate cytotoxic drugs for liver cancer treatment has evoked immense interest with respect to their convenience in biomedical application. Herein, we engineered multifunctional Janus nanocomposites, characterized by a head of magnetic Fe3O4 and a body of mesoporous SiO2 containing doxorubicin (DOX) as "nano-bullets" (M-MSNs-DOX). This nanodrug formulation possessed nanosize with controlled aspect-ratio, defined abundance in pore structures, and superior magnetic properties. M-MSN-DOX was determined to induce selective growth inhibition to the cancer cell under magnetic field rather than human normal cells due to its preferable endocytosis by the tumor cells and pH-promoted DOX release in the interior of cancer cells. Ultimately, both subcutaneous and orthotropic liver tumor models in mice have demonstrated that the proposed Janus nano-bullets imposed remarkable suppression of the tumor growth and significantly reduced systematic toxicity. Taken together, this study demonstrates an intriguing targeting strategy for liver cancer treatment based on a novel Janus nano-bullet, aiming for utilization of nanotechnology to obtain safe and efficient treatment of liver cancer. PMID- 27258483 TI - Photothermal combined gene therapy achieved by polyethyleneimine-grafted oxidized mesoporous carbon nanospheres. AB - Combining controllable photothermal therapy and efficacious gene therapy in a single platform holds great promise in cancer therapy due to the enhanced combined therapeutic effects. Herein, polyethyleneimine-grafted oxidized mesoporous carbon nanospheres (OP) were developed for combined photothermal combined gene therapy in vitro and in vivo. The synthesized OP was characterized to have three dimensional spherical structure with uniformed diameter, ordered mesopores with graphitic domains, high water dispersion with zeta potential of +22 mV, and good biocompatibility. Consequently, OP was exploited as the photothermal convertor with strong NIR absorption and the gene vector via electrostatic interaction, which therefore cannot only deliver the therapeutic gene (pING4) to tumors for gene therapy, but also can eliminate the tumors by photothermal ablation. Moreover, the improved gene therapy accompanied by the NIR photothermally enhanced gene release was also well achieved based on OP. The excellent combined therapeutic effects demonstrated in vitro and in vivo suggested the OP's potential for cancer therapy. PMID- 27258484 TI - Hybridization-based aptamer labeling using complementary oligonucleotide platform for PET and optical imaging. AB - Aptamers are promising next-generation ligands used in molecular imaging and theragnosis. Aptamers are synthetic nucleic acids that can be held together with complementary sequences by base-pair hybridization. In this study, the complementary oligonucleotide (cODN) hybridization-based aptamer conjugation platform was developed to use aptamers as the molecular imaging agent. The cODN was pre-labeled with fluorescent dye or radioisotope and hybridized with a matched sequence containing aptamers in aqueous conditions. The cODN platform hybridized aptamers exhibited good serum stability and specific binding affinity towards target cancer cells both in vitro and in vivo. These results suggest that the newly designed aptamer conjugation platform offers great potential for the versatile application of aptamers as molecular imaging agents. PMID- 27258486 TI - A novel near-infrared fluorescent probe for H2O2 in alkaline environment and the application for H2O2 imaging in vitro and in vivo. AB - H2O2 as one of the most important ROS (Reactive Oxygen Species) has more attack activity to biomolecules such as DNA, RNA, protein and enzyme in alkaline environment and leads to a series of disease. However, no attention has been paid to the fluorescent detection of H2O2 in alkaline environment in the past. Herein, we reported the first ratiometric near-infrared fluorescent probe based on a boric acid derivative of Changsha near-infrared dye (CSBOH) for H2O2 detection in alkaline condition and the application for H2O2 imaging in vivo. ICT (intra molecular charge transfer) mechanism was used in CSBOH to modulate the fluorescence change. The photophysical change of CSBOH was investigated by comparison with a phenol derivative of Changsha near-infrared dye (CSOH), a structural analogue bearing phenol group. In the presence of H2O2, CSBOH exhibited remarkably different fluorescence change at 650 nm and 720 nm when excited by 560 nm and 670 nm light respectively in alkaline buffer and showed high selectivity toward H2O2. Cellular experiments demonstrate that CSBOH can image endogenously generated H2O2 in macrophages and A431 cells. In vivo experiment demonstrates that both CSOH and CSBOH can be used for bio-imaging, and CSBOH can image H2O2 in living animal successfully. PMID- 27258485 TI - Nanoprobes for two-photon excitation time-resolved imaging of living animals: In situ analysis of tumor-targeting dynamics of nanocarriers. AB - Great challenges remain in the noninvasive luminescence imaging analysis of tumor targeting dynamics of nanocarriers in living animals which is of significance for the development of anti-cancer nanomedicine. In this work, luminescent nanoparticles Eu(tta)3bpt@SMA (dav = 15 nm), which exhibited good water dispersion stability and high yields of red Eu-luminescence under near-infrared two-photon excitation, were prepared by a modified microfluidic mixing method in the absence of surfactants. Tumor-targeting agents, Arg-Gly-Asp-D-Phe-Lys (cRGD) polypeptide or transferrin (Tf), were then anchored on the nanoparticle surfaces to form the desired nanocarriers Eu@SMA-RGD or Eu@SMA-Tf. The tumor-targeting processes of the prepared nanocarriers in intact living mice were analyzed on a home-built two-photon excitation time-resolved (TPE-TR) imaging apparatus having a wide view filed. The TPE-TR strategy could effectively suppress the interference from biological autofluorescence, which allowed the targeted domains to be visualized with a high signal-to-noise ratio. It was found that the tumor tissue trapping efficacy of Eu@SMA-RGD was much higher than that of Eu@SMA-Tf, and the desorption process from the tumor tissues of Eu@SMA-RGD was slower than that of Eu@SMA-Tf. The methods developed in this work pave a way to investigate the in vivo tumor-targeting dynamics of nanocarriers by noninvasive luminescence imaging of living animals. PMID- 27258487 TI - Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer: An International Multi-Institutional Study. AB - Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer.An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate.The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively.Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID- 27258489 TI - Prevalence of Comorbidities in Asthma and Nonasthma Patients: A Meta-analysis. AB - This study compares the prevalence rates of comorbidities between asthma and nonasthma control patients reported in the literature.Literature was searched in several electronic databases. After the selection of studies by following precised eligibility criteria, meta-analyses of odds ratios were carried out with subgroup and sensitivity analyses.Eleven studies studying 117,548 asthma patients compared with 443,948 non-asthma controls were included in the meta-analysis. The prevalence of cardiovascular comorbidities (odds ratio (OR): [95% CI] 1.90 [1.70, 2.14]; P < 0.00001), cerebrovascular comorbidities (OR 1.44 [1.29, 1.60]; P < 0.00001), obesity (OR 1.51 [1.14, 2.01]; P < 0.00001), hypertension (OR 1.66 [1.47, 1.88]; P < 0.00001, diabetes (OR 1.25 [1.08, 1.44]; P < 0.00001), other metabolic and endocrine comorbidities (OR 1.60 [1.40, 1.83]; P < 0.00001), psychiatric and neurological comorbidities (OR 1.62 [1.44, 1.82]; P < 0.00001), gut and urinary comorbidities (OR 1.91 [1.47, 2.49]; P < 0.00001),), cancer (OR 1.17 [1.10, 1.25]; P < 0.00001), and respiratory comorbidities (OR 5.60 [4.22, 7.44]; P < 0.00001) were significantly higher in the asthma patients in comparison with nonasthma controls.Asthma is associated with significantly higher comorbidities including cardio-/cerebrovascular diseases, obesity, hypertension, diabetes, psychiatric and neurological comorbidities, gut and urinary conditions, cancer, and respiratory problems other than asthma. Respiratory comorbidities are found 5 times more prevalent in asthma than in non-asthma patients. PMID- 27258488 TI - Effects of Statins on Bone Mineral Density and Fracture Risk: A PRISMA-compliant Systematic Review and Meta-Analysis. AB - Although observational studies have identified the protective effect of statins on bone health, the effects remain controversial in randomized controlled trials (RCTs). We conducted a meta-analysis of RCTs to evaluate the effects of statins on bone mineral density (BMD) and fracture risk among adults.We searched electronic databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) and conducted a bibliography review to identify articles published until May, 2015.Studies included in this meta-analysis should be randomized controlled trials conducted in adults, using statins in the intervention group. Information on changes in BMD or odds ratio, relative risk or hazard ratio (HR) for fracture risk with the corresponding 95% confidence interval (CI) was provided.Two investigators independently reviewed the title or abstract, further reviewed the full-texts and extracted information on study characteristics and study outcomes. Net change estimates of BMD and pooled HR of fracture risk comparing the intervention group with the control group were estimated across trials using random-effects models.Of the relevant 334 citations, 7 trials (including 27,900 randomized participants in total) meeting the eligibility criteria were included. Of the 7 trials, 5 were conducted to assess the association of statins use with BMD change and 2 with fracture risk. Compared with the control group, statins use was associated with significant increase in BMD of 0.03 g/cm (95% CI: 0.006, 0.053; I = 99.2%; P < 0.001), but null association with fracture risk, with the pooled HR of 1.00 (95% CI: 0.87, 1.15; I = 0; P = 0.396). Sensitivity analyses revealed that the associations were consistent and robust.The effect of statins use on bone health among subpopulation could not be identified due to limited number of trials.These findings provide evidence that statins could be used to increase BMD other than decreasing fracture risk in participant with dyslipidemia. In addition, further trials with the primary outcome of bone health-related measurements in subpopulation are warranted to ensure the effect of statins use. PMID- 27258490 TI - Congenital Nephrogenic Diabetes Insipidus Presented With Bilateral Hydronephrosis and Urinary Infection: A Case Report. AB - Nephrogenic diabetes insipidus (NDI) is a condition resulting from the kidney's impaired response to circulating antidiuretic hormone (ADH), leading to polydipsia and polyuria. Urinary tract dilatation caused by NDI is a rare situation. Here, we report a case of congenital NDI presented with bilateral hydronephrosis.A 15-year-old boy complaining a history of intermittent fever was admitted to Peking Union Medical College Hospital. He voided 10 to 15 L of urine daily. Radiographic examination revealed severe dilatation of bilateral renal pelvis, ureter, and bladder. Urinalysis shows hyposthenuria.He was diagnosed NDI since born. Transient insertion of a urethral catheter helped to relieve fever. Medical therapy of hydrochlorothiazide and amiloride was prescribed and effective.Dilatation of urinary tract caused by diabetes insipidus is rare, but may be present in severe condition. Therefore, it is crucial for clinicians to perform early treatment to avoid impairment of renal function. PMID- 27258492 TI - Validation of the Model for End-Stage Liver Disease Score Criteria in Urgent Liver Transplantation for Acute Flare Up of Hepatitis B. AB - Acute flare up of hepatitis B in noncirrhotic liver with rapid liver function deterioration is a critical condition. This flare up of hepatitis B may be subsided under medical treatments, otherwise urgent liver transplantation is needed. However, the necessity of urgent liver transplantation is hard to decide. In this institute, the indications of urgent liver transplantation for acute flare up of hepatitis B in noncirrhotic liver were settled according to the model for end-stage liver disease (MELD) scores: once upon MELD scores >=35 (criterion 1) or MELD score < 35 at beginning and increased in the subsequent 1 to 2 weeks (criterion 2). This study was to examine whether MELD score criteria for liver transplantation were valid in such an urgent condition. Eighty-three patients having acute flare up of hepatitis B virus with total bilirubin >=17.5 mg/dL were included in this study. Among 83 patients, 20 patients met criterion 1. Five patients were transplanted and 15 patients died of liver failure with a median survival of 17 days. Fifty-one patients met criterion 2. Nineteen were transplanted, 30 patients died of liver failure with a median survival of 23.5 days, and 2 patients recovered from this critical condition. The other 12 patients did not meet criteria 1 and 2, and urgent liver transplantation was spared although 5 patients needed liver transplantation in subsequent 2 to 3 months. Therefore, the sensitivity of MELD score criteria for urgent liver transplantation was 100% and specificity was 85.7%. In conclusion, determination of urgent liver transplantation for hepatitis B with acute liver failure is crucial. MELD score criteria are valid to make a decision of urgent liver transplantation for hepatitis B patients with acute flare up and liver failure. PMID- 27258491 TI - Refined Phenotyping of Modic Changes: Imaging Biomarkers of Prolonged Severe Low Back Pain and Disability. AB - Low back pain (LBP) is the world's most disabling condition. Modic changes (MC) are vertebral bone marrow changes adjacent to the endplates as noted on magnetic resonance imaging. The associations of specific MC types and patterns with prolonged, severe LBP and disability remain speculative. This study assessed the relationship of prolonged, severe LBP and back-related disability, with the presence and morphology of lumbar MC in a large cross-sectional population-based study of Southern Chinese.We addressed the topographical and morphological dimensions of MC along with other magnetic resonance imaging phenotypes (eg, disc degeneration and displacement) on the basis of axial T1 and sagittal T2-weighted imaging of L1-S1. Prolonged severe LBP was defined as LBP lasting >=30 days during the past year, and a visual analog scale severest pain intensity of at least 6/10. An Oswestry Disability Index score of 15% was regarded as significant disability. We also assessed subject demographics, occupation, and lifestyle factors.In total, 1142 subjects (63% females, mean age 53 years) were assessed. Of these, 282 (24.7%) had MC (7.1% type I, 17.6% type II). MC subjects were older (P = 0.003), had more frequent disc displacements (P < 0.001) and greater degree of disc degeneration (P < 0.001) than non-MC subjects. In adjusted models, any MC (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.01-2.18), MC affecting whole anterior-posterior length (OR 1.62, 95% CI 1.04-2.51), and MC affecting 2/3 posterior length (OR 2.79, 95% CI 1.17-6.65) were associated with prolonged severe LBP. Type I MC tended to associate with pain more strongly than type II MC (OR 1.80, 95% CI 0.94-3.44 vs OR 1.36, 95% CI 0.88-2.09, respectively). Any MC (OR 1.47, 95% CI 1.04-2.10), type II MC (OR 1.56, 95% CI 1.06-2.31), MC affecting 2/3 posterior length (OR 2.96, 95% CI 1.27-6.89), and extensive MC (OR 1.95, 95% CI 1.21-3.15) were associated with disability. The strength of the associations increased with the number of MC.This large-scale study is the first to definitively note MC types and specific morphologies to be independently associated with prolonged severe LBP and back-related disability. This proposed refined MC phenotype may have direct implications in clinical decision-making as to the development and management of LBP. Understanding of these imaging biomarkers can lead to new preventative and personalized therapeutics related to LBP. PMID- 27258493 TI - Inhaled Corticosteroids Use Is Not Associated With an Increased Risk of Pregnancy Induced Hypertension and Gestational Diabetes Mellitus: Two Nested Case-Control Studies. AB - There have been concerns that systemic corticosteroid use is associated with pregnancy-induced hypertension (PIH) and diabetes mellitus. However, the relationship between inhaled corticosteroids (ICSs) and the risk of PIH has not been fully examined, and there was no study investigating the association between ICS use and the development of gestational diabetes mellitus (GDM). The aims of the study are to determine whether the use of ICSs during pregnancy increases the risk of PIH and GDM in women.We conducted 2 nested case-control studies utilizing the nationwide insurance claims database of the Health Insurance Review and Assessment Service (Seoul, Republic of Korea), in which 1,306,281 pregnant women who delivered between January 1, 2009 and December 31, 2011 were included. Among them, PIH cases and GDM cases were identified and matched controls were included. Conditional logistic regression analyses adjusted by other concomitant drugs use during and before pregnancy and confounding covariates including comorbidities were performed.Total 43,908 PIH cases and 219,534 controls, and 34,190 GDM cases and 170,934 control subjects were identified. When other concomitant drugs use during pregnancy was adjusted, ICS use was associated with an increased rate of PIH (adjusted odds ratio, 1.40 [95% CI, 1.05-1.87]). ICS medication possession ratios and cumulative doses were associated with an increased risk of PIH. However, the statistical significance was not found in other models. In both unadjusted and adjusted multivariable models, ICSs use was not associated with increase in the risk of GDM.ICSs use is not associated with an increased risk of PIH and GDM. PMID- 27258495 TI - Impact of Type of Surgery on Survival Outcome in Patients With Early Gallbladder Cancer in the Era of Minimally Invasive Surgery: Oncologic Safety of Laparoscopic Surgery. AB - Laparoscopic surgery has been widely accepted as a feasible and safe treatment modality in many cancers of the gastrointestinal tract. However, most guidelines on gallbladder cancer (GBC) regard laparoscopic surgery as a contraindication, even for early GBC. This study aims to evaluate and compare recent surgical outcomes of laparoscopic and open surgery for T1(a,b) GBC and to determine the optimal surgical strategy for T1 GBC.The study enrolled 197 patients with histopathologically proven T1 GBC and no history of other cancers who underwent surgery from 2000 to 2014 at 3 major tertiary referral hospitals with specialized biliary-pancreas pathologists and optimal pathologic handling protocols. Median follow-up was 56 months. The effects of depth of invasion and type of surgery on disease-specific survival and recurrence patterns were investigated.Of the 197 patients, 116 (58.9%) underwent simple cholecystectomy, including 31 (15.7%) who underwent open cholecystectomy and 85 (43.1%) laparoscopic cholecystectomy. The remaining 81 (41.1%) patients underwent extended cholecystectomy. Five-year disease-specific survival rates were similar in patients who underwent simple and extended cholecystectomy (96.7% vs 100%, P = 0.483), as well as being similar in patients in the simple cholecystectomy group who underwent open and laparoscopic cholecystectomy (100% vs 97.6%, P = 0.543). Type of surgery had no effect on recurrence patterns.Laparoscopic cholecystectomy for T1 gallbladder cancer can provide similar survival outcomes compared to open surgery. Considering less blood loss and shorter hospital stay with better cosmetic outcome, laparoscopic cholecystectomy can be justified as a standard treatment for T1b as well as T1a gallbladder cancer when done by well-experienced surgeons based on exact pathologic diagnosis. PMID- 27258494 TI - Risks and Benefits of Dual Antiplatelet Therapy Beyond 12 Months After Coronary Stenting: A Prospective Randomized Cohort Study. AB - The optimal duration of dual antiplatelet therapy (DAT) after coronary stenting remains poorly define. The aim of this study was to evaluate the impact of longer than 24 months DAT in patients who received drug-eluting and bare-metal stents.A total of 1010 individuals who underwent elective, urgent or emergency coronary angioplasty with intended stent implantation at reference or specialized cardiac hospitals were randomized to receive long-term and short-term DAT to determine the benefits and adverse effects of long-term DAT. Total of 508 patients were randomized to long-term and 502 patients to <1 year DAT, and all of them were followed for more than 36 months for major adverse cardiac and cerebvascular events and bleeding major adverse cardiac and cerebvascular events (MACCE)Mean age of the 1010 patients (364 women and 646 men) was 60 years. Stent reocclusion occurred in 15 patients. Mean Syntax score was 23.00 +/- 5.08 for whole samples, 25.00 +/- 5.27 in 28 patients with MACCE and 23 +/- 5.00 in 982 patients without MACCE (P = 0.057). According to all specified bleeding definitions, clopidogrel therapy for >12 months was not associated with a greater risk of hemorrhage. A regimen of >12 months of clopidogrel therapy in patients who had received drug eluting or bare-metal stents did not differ significantly from a regimen of <12 months on clopidogrel with regard to MACCE.Long-term DAT might not significantly affect the reduction in the risk of death from any cause, myocardial infarction, or stroke, and not associated with minor or major bleeding events. PMID- 27258496 TI - Case Report of Birt-Hogg-Dube Syndrome: Germline Mutations of FLCN Detected in Patients With Renal Cancer and Thyroid Cancer. AB - Birt-Hogg-Dube (BHD) is a rare autosomal dominant inherited syndrome that is characterized by the presence of fibrofolliculomas and/or trichodiscomas, pulmonary cysts, spontaneous pneumothorax, and renal tumors. Here, the 2 patients we reported with renal cell carcinomas and dermatological features were suspected to be suffering from BHD syndrome. Blood samples of these patients were sent for whole exon sequencing performed by Sanger sequencing. Eight mutations, including 5 mutations, which were mapped in noncoding region, 1 synonymous mutation, and 2 missense mutations, were detected in the FLCN gene in both patients. The 2 missense mutations, predicted to be disease-causing mutation or affecting protein function by MutationTaster and SIFT, confirmed the diagnosis. In addition, the 2 patients were also affected with papillary thyroid cancer. Total thyroidectomy and prophylactic bilateral central lymph node dissection were performed for them and the BHD-2 also received lateral lymph node dissection. Pathology reports showed that the patients had lymph node metastasis in spite of small size of thyroid lesions.The 2 missense mutations, not reported previously, expand the mutation spectrum of FLCN gene associated with BHD syndrome. For the thyroid cancer patients with BHD syndrome, total thyroidectomy and prophylactic bilateral central lymph node dissection may be suitable and the neck ultrasound may benefit BHD patients and their family members. PMID- 27258498 TI - Racial Disparities in Treatment Rates for Chronic Hepatitis C: Analysis of a Population-Based Cohort of 73,665 Patients in the United States. AB - Chronic hepatitis C (CHC) disproportionately affects racial minorities in the United States (US). Although prior studies have reported lower treatment rates in Blacks than in Caucasians, the rates of other minorities remain understudied. We aimed to examine antiviral treatment rates by race and to evaluate the effect of other demographic, medical, and psychiatric factors on treatment rates. We performed a population-based study of adult CHC patients identified via ICD-9CM query from OptumInsight's Data Mart from January 2009 to December 2013. Antiviral treatment was defined by pharmaceutical claims for interferon and/or pegylated interferon. A total of 73,665 insured patients were included: 51,282 Caucasians, 10,493 Blacks, 8679 Hispanics, and 3211 Asians. Caucasians had the highest treatment rate (10.7%) followed by Blacks (8.8%), Hispanics (8.8%), and Asians (7.9%, P < .001). Hispanics had the highest cirrhosis rates compared with Caucasians, Blacks, and Asians (20.7% vs 18.3%, 17.1%, and 14.3%, respectively). Caucasians were the most likely to have a psychiatric comorbidity (20.1%) and Blacks the most likely to have a medical comorbidity (44%). Asians were the least likely to have a psychiatric (6.4%) or medical comorbidity (26.9%). On multivariate analysis, racial minority was a significant predictor of nontreatment with odds ratios of 0.82 [confidence interval (CI): 0.74-0.90] for Blacks, 0.87 (CI: 0.78-0.96) for Hispanics, and 0.73 (CI: 0.62-0.86) for Asians versus Caucasians. Racial minorities had lower treatment rates than Caucasians. Despite fewer medical and psychiatric comorbidities and higher incomes and educational levels, Asians had the lowest treatment rates. Hispanics also had lower treatment rates than Caucasians despite having higher rates of cirrhosis. Future studies should aim to identify underlying racial-related barriers to hepatitis C virus treatment besides socioeconomic status and medical or psychiatric comorbidities. PMID- 27258497 TI - Prevalence and Associated Factors of Anxiety and Depressive Symptoms Among Bereaved Family Members of Cancer Patients in Korea: A Nation-Wide Cross Sectional Study. AB - Bereaved family members of cancer patient are at risk of having psychological problems such as anxiety and depression. However, prevalence and associated factors of anxiety and depressive symptoms among this population have not been explored in Korea.We conducted a nation-wide cross-sectional questionnaire survey of 3522 bereaved family members of cancer patients who died at 44 hospice palliative care unit (HPCU) in Korea in 2012. The questionnaire comprised the Hospital Anxiety and Depression Scale (HADS) and Good Death Inventory (GDI). Deceased patient's age, sex, primary site of cancer, duration of stay at HPCU, awareness of terminal status, bereaved family member's age, sex, and relation to the deceased were collected from Korean Terminal Cancer Patients Information System.1121 returned questionnaires were analyzed (response rate, 31.8%). Using a cut-off value of 8 for HADS subscale, the prevalence of anxiety and depressive symptoms was 48.0% and 57.6%, respectively. Mean scores for HADS-A and HADS-D were 7.88 +/- 4.87 and 8.91 +/- 4.82, respectively. Among the bereaved, older age, being a spouse to the deceased, family members of younger patient, and negative score for a few GDI items were significantly associated with an increased risk of having anxiety or depressive symptoms in the multivariate logistic analysis.In conclusion, we noted the high prevalence of anxiety and depressive symptoms among the bereaved of cancer patients and identified associated factors for these psychological morbidities. Systematic efforts are needed to improve the mental health of the bereaved family members of cancer patients. PMID- 27258499 TI - Overexpression of MutSalpha Complex Proteins Predicts Poor Prognosis in Oral Squamous Cell Carcinoma. AB - The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSalpha complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 +/- 15.21 and 31.46 +/- 22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSalpha complex expression. In the multivariable analysis, high expression of the MutSalpha complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSalpha complex may constitute a molecular marker for the poor prognosis of OSCC. PMID- 27258500 TI - Declining Inconsistent Condom Use but Increasing HIV and Syphilis Prevalence Among Older Male Clients of Female Sex Workers: Analysis From Sentinel Surveillance Sites (2010-2015), Guangxi, China. AB - Clients of female sex workers (CFSWs) are a bridge population for the spread of HIV and syphilis to low or average risk heterosexuals. Most studies have examined the point prevalence of these infections in CFSWs. Limited evidence suggests that older age CFSWs are at a higher risk of acquiring sexually transmitted diseases compared with younger clients. Thus, we sought to describe long-term trends in HIV, syphilis, and hepatitis C (HCV) to better understand how these infections differ by sex worker classification and client age. We also examined trends in HIV, syphilis, and HCV among categories of female sex workers (FSWs).We conducted serial cross-sectional studies from 2010 to 2015 in Guangxi autonomous region, China. We collected demographic and behavior variables. FSWs and their clients were tested for HIV, syphilis, and HCV antibodies. Positive HIV and syphilis serologies were confirmed by Western blot and rapid plasma regain, respectively. Clients were categorized as middle age (40-49 years) and older clients (>=50 years). FSWs were categorized as high-tier, middle-tier, or low-tier based on the payment amount charged for sex and their work venue. Chi-square test for trends was used for testing changes in prevalence over time.By 2015, low-tier FSWs (LTFSWs) accounted for almost half of all FSWs; and they had the highest HIV prevalence at 1.4%. HIV prevalence declined significantly for FSWs (high-tier FSW, P = 0.003; middle-tier FSWs; P = 0.021; LTFSWs, P < 0.001). Syphilis infections significantly declined for FSWs (P < 0.001) but only to 7.3% for LTFSWs. HCV and intravenous drug use were uncommon in FSWs. HIV prevalence increased for older age clients (1.3%-2.0%, P = 0.159) while syphilis prevalence remained stable. HCV infections were halved among older clients in 3 years (1.7% 0.8%, P < 0.001). Condom use during the last sexual encounter increased for FSWs and CFSWs. Few clients reported sex with men or intravenous drug use. Clients preferred LTFSWs, especially older clients (81.9%).Our results suggest that HIV and syphilis infections are increasing in older clients who prefer LTFSWs. HIV and syphilis are likely increasing in Guangxi Province through heterosexual transmission. PMID- 27258501 TI - Key to Prevention of Bradycardia: Be Relax Postoperatively: A Case Report. AB - Hypotension and bradycardia are commonly observed after the spinal anesthesia and various mechanisms have been postulated for these hemodynamic changes.A middle aged otherwise healthy male Caucasian patient developed several episodes of bradycardia postoperatively after the umbilical hernia repair under subarachnoid block (SAB) while trying to lean forward and move his legs. Episodes were aborted when patient was advised to relax in supine position.The common mechanism of bradycardia and hypotension under SAB is postulated as sympathetic blockade, decrease venous return, and parasympathetic over-dominance leading to a decrease in right arterial pressure and pressure in the great veins as they enter the right atrium. But over time, the parasympathetic inhibition is usually withdrawn first, leading to the risk of severe bradycardia that is probably favored by the reverse Trendelenburg position as described in our case.Postoperative severe hemodynamic changes can occur even under stable spinal anesthesia; however, can be prevented by vigilant monitoring and simple maneuver which includes maintenance of relax posture on the bed. PMID- 27258502 TI - A Case Report: Large Trichobezoar Causing Rapunzel Syndrome. AB - Rapunzel syndrome is very rare gastric foreign bodies that occur in children. It is a severe condition of a gastric trichobezoar with a long tail that passes into the small intestine. Here, we present the case of an 8-year-old girl with Rapunzel syndrome due to a very large (7 * 7 * 30 cm) gastric trichobezoar. The patient had trichotillomania and trichophagia for 1 year prior to presentation. Ideally, small bezoars are removed through a minimally invasive method, such as endoscopic fragmentation. However, large trichobezoars, including those in Rapunzel syndrome, can only be managed with open surgical extraction, despite the large scars that may result.We report a case of Rapunzel syndrome with a large bezoar that was surgically removed after it was endoscopically cauterized with argon plasma. Endoscopic precutting was used to effectively reduce the size of the bezoar. PMID- 27258503 TI - Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis. AB - The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome.A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome.The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%).In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options. PMID- 27258504 TI - Design and Rationale of the APELOT Trial: A Randomized, Open-Label, Multicenter, Phase IV Study to Evaluate the Antiplatelet Effect of Different Loading Dose of Ticagrelor in Patients With Non-ST Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention. AB - Ticagrelor is a direct acting on the P2Y12 receptor blocker, which provides faster and greater platelet inhibition than clopidogrel. However, several studies suggested that in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention (PCI), ticagrelor exhibits initial delay in the onset of antiplatelet action. Unlike ST-segment elevation myocardial infarction, in non-ST-segment elevation acute coronary syndrome (NSTE-ACS), management pathways are highly variable, and some patients may require surgery. Effect of higher loading dose (LD) of ticagrelor in patients with NSTE-ACS in providing faster and stronger inhibition of platelet aggregation is unknown and needs to be explored further.The AntiPlatelet Effect of different Loading dOse of Ticagrelor trial is an interventional, randomized, open-label, multicenter, phase IV trial designed to evaluate whether a high LD (360 mg) of ticagrelor compared with the conventional LD (180 mg) will result in a higher inhibition of platelet aggregation without increasing bleeding events in NSTE-ACS participants undergoing PCI.A total of 250 NSTE-ACS participants will be randomized to receive a ticagrelor LD (360 or 180 mg), followed by a maintenance dose of 90 mg twice a day (bid) starting 12 hours after the LD. The primary endpoint is platelet reactivity index measured by vasodilator-stimulated phosphoprotein phosphorylation 2 hours after the LD, and the secondary endpoints include occurrence of periprocedural myocardial infarction and bleeding events.The AntiPlatelet Effect of different Loading dOse of Ticagrelor trial will provide important information on the risks and benefits of a high LD (360 mg) of ticagrelor in achieving a faster and stronger platelet inhibition compared with the conventional LD (180 mg) in NSTE-ACS patients undergoing PCI. PMID- 27258505 TI - Urine Output During Cardiopulmonary Bypass Predicts Acute Kidney Injury After Cardiac Surgery: A Single-Center Retrospective Analysis. AB - Urine output is closely associated with renal function and has been used as a diagnostic criterion for acute kidney injury (AKI). However, urine output during cardiopulmonary bypass (CPB) has never been identified as a predictor of postoperative AKI. Considering altered renal homeostasis during CPB, we made a comprehensible approach to CPB urine output and evaluated its predictability for AKI.Patients undergoing cardiovascular surgery with the use of CPB, between January 2009 and December 2011, were retrospectively reviewed. AKI was defined as an increase in serum creatinine >=0.3 mg/dL in the first postoperative 48 hours. We extrapolated a possible optimal amount of urine output from the plot of probability of AKI development according to CPB urine output. After separating patients by the predicted optimal value, we performed stepwise logistic regression analyses to find potential predictors of AKI in both subgroups.A total of 696 patients were analyzed. The amount of CPB urine output had a biphasic association with the incidence of AKI using 4 mL/kg/h as a boundary value. In a multivariate logistic regression to find predictors for AKI in entire patients, CPB urine output did not show statistical significance. After separating patients into subgroups with CPB urine output below and over 4 mL/kg/h, it was identified as an independent predictor for AKI with the odds ratio of 0.43 (confidence interval 0.30-0.61) and 1.11 (confidence interval 1.02-1.20), respectively.The amount of urine output during CPB with careful analysis may serve as a simple and feasible method to predict the development of AKI after cardiac surgery at an early time point. PMID- 27258506 TI - Posterior Reversible Encephalopathy Syndrome Complicating Traumatic Pancreatitis: A Pediatric Case Report. AB - We are reporting a case of posterior reversible encephalopathy syndrome (PRES) developed in an unusual clinical scenario without the presence of the most described symptoms. PRES is a neurological and radiological syndrome described in many different clinical conditions. In children it has been mostly reported in association with hematological and renal disorders.Our patient was a 15 years old boy, admitted to our intensive care unit for pancreatitis after blunt abdominal trauma.During the stay in the intensive care unit, he underwent multiple abdominal surgical interventions for pancreatitis complications. He had a difficult management of analgesia and sedation, being often agitated with high arterial pressure, and he developed a bacterial peritonitis. After 29 days his neurological conditions abruptly worsened with neuroimaging findings consistent with PRES. His clinical conditions progressively improved after sedation and arterial pressure control.He was discharged at home with complete resolution of the neurological and imaging signs 2 months later.The pathophysiology of PRES is controversial and involves disordered autoregulation ascribable to hypertension and endothelial dysfunction. In this case both hypertension and endothelial activation, triggered by sepsis and pancreatitis, could represent the culprits of PRES onset. Even if there is no specific treatment for this condition, a diagnosis is mandatory to start antihypertensive and supportive treatment. We are therefore suggesting to consider PRES in the differential diagnosis of a neurological deterioration preceded by hypertension and/or septic state, even without other "typical" clinical features. PMID- 27258507 TI - Clinic and Home Blood Pressure Lowering Effect of an Angiotensin Receptor Blocker, Fimasartan, in Postmenopausal Women with Hypertension. AB - Angiotensin receptor blockers may be an appropriate first-line agent for postmenopausal women with hypertension because the activation of renin angiotensin-aldosterone system is suggested as one possible mechanism of postmenopausal hypertension. However, there are few studies substantiating this effect. This study aimed to investigate clinic and home blood pressure (BP) lowering effect of fimasartan, a new angiotensin receptor blocker, in postmenopausal women with hypertension.Among patients with hypertension enrolled in K-Mets Study, 1373 women with fimasartan as a first antihypertensive drug and 3-months follow-up data were selected. They were divided into 2 groups; premenopausal women (pre-MPW; n = 382, 45.3 +/- 4.6 years) and postmenopausal women (post-MPW; n = 991, 60.9 +/- 8.2 years).Baseline clinic systolic BP was not different (pre-MPW; 152.9 +/- 15.2 vs. post-MPW; 152.8 +/- 13.5 mm Hg), but diastolic BP was lower in post-MPW (pre-MPW; 95.7 +/- 9.4 vs. post-MPW; 91.9 +/- 9.4 mm Hg, P <0.001). After 3-month treatment, clinic BP declined effectively without significant differences between 2 groups (Deltasystolic/diastolic BP: pre MPW; -25.7 +/- 17.7/-14.2 +/- 11.3 vs. post-MPW; -25.7 +/- 16.3/-13.1 +/- 10.9 mm Hg). Home morning and evening systolic BP decreased similarly in both groups (Deltamorning/evening systolic BP: pre-MPW; -21.3 +/- 17.9/-23.1 +/- 15.8 vs. post-MPW; -20.4 +/- 17.3/-20.2 +/- 19.2 mm Hg). Fimasartan also significantly decreased the standard deviations of home morning and evening systolic BP of pre MPW and post-MPW.Fimasartan was a similarly effective BP lowering agent in both post-MPW and pre-MPW with hypertension, and it also decreased day-to-day BP variability. PMID- 27258509 TI - Distal Femoral Oblique Fracture in a Young Male Soldier: Case Report of an Unusual Presentation. AB - Here, we report a case of a distal femoral fracture in a 23-year-old male army cadet who presented to the Accident and Emergency department following a twisting injury while participating in a routine military marching exercise. A pathological fracture was considered but this suspicion was put to rest following thorough investigations, leaving only a diagnosis of a nontraumatic spontaneous femoral fracture.To our knowledge, there have been no reported cases of distal femoral fractures associated with nontraumatic military exercises, with the majority of injuries instead related to stress fractures. A vigilant literature search yielded no cases of similar injury nature, which is the primary reason we believe that those interested in orthopaedics or military doctors would find themselves drawn to this case.The patient presented with severe pain in his left thigh and on examination there was a deformity of his left thigh.In terms of investigations, a bone profile, plain film radiographs, C-reactive protein, erythrocyte sedimentation rate, and tumor markers were all preformed and proved unremarkable. The definitive treatment was by open reduction and internal fixation.Femoral fractures often require significant amounts of force, particularly in young, healthy individuals. Generally, these injuries in this demographic follow high-energy traumas, with the lion's share occurring following a road traffic accident or other high-speed impact. More often than not, the treatment is surgical. Given the extraordinary manner of this such, one must be attentive and exhaustive in their investigation of such presentations. PMID- 27258508 TI - Identification of High-Risk Subgroups of Patients With Oral Cavity Cancer in Need of Postoperative Adjuvant Radiotherapy or Chemo-Radiotherapy. AB - Patients with oral cavity squamous cell carcinoma (OSCC) undergoing surgery are recommended to receive adjuvant radiation therapy with or without chemotherapy if there are unfavorable prognostic factors. A positive resection margin (PRM) and extra-capsular extension (ECE) of lymph nodes are well-known major prognostic factors. However, there is no agreement on whether oral cavity cancer patients should receive postoperative chemo-radiotherapy (CCRT) if they present with other risk factors or a combination of 2 or more risk factors. In this study, we investigated this issue and provide suggestions for adjuvant treatments.From January 2002 to December 2013, 567 OSCC patients who had undergone radical surgery were retrospectively reviewed. The 5-year loco-regional control (LRC), distant metastasis-free (DMF), disease-free survival (DFS), and overall survival (OS) were analyzed.In univariate analysis, pathological T classification, positive node, tumor depth, ECE, lymphatic or vascular or perineural invasion and histology grade are significant prognostic factors for LRC, DMF, DFS, or OS. By multivariate analysis, pathological T4 (pT4), positive node, positive surgical margin are prognostic factors for LRC. pT4, positive node and lymphatic invasion predicted for higher rate of distant metastasis. pT4, positive node, and poor differentiation tumor were prognostic factors for DFS. pT4, positive nodes, and ECE were prognostic factors for OS. These factors were used to define risk groups. We proposed PRM and ECE as major risk factors and pT4, positive nodes, close margin (<= 5 mm, > 1 mm), tumor depth >= 1 cm, lymphatic invasion, vascular invasion, perineural invasion, and poor differentiation as minor risk factors. By subgroups analysis, 192 patients with at least 2 minor prognostic factors and no other major risk factors, postoperative radiotherapy (RT), or CCRT yielded significantly better 5-year LRC, DFS, and OS compared to surgery only group. For 179 patients with at least 3 minor prognostic factors and/or at least 1 major risk factor, patients receiving postoperative CCRT showed significantly better 5 year LRC, DFS, and OS compared with post-OP RT or surgery alone.Patients with 2 minor risk factors should receive postoperative RT. For patients with PRM, ECE, or >2 minor risk factors, postoperative CCRT is recommended. PMID- 27258510 TI - Estimated Glomerular Filtration Rate Trajectories in HIV-Infected Subjects Treated With Different Ritonavir-Boosted Protease Inhibitors and Tenofovir Disoproxil Fumarate or Abacavir. AB - The aim of the study was to evaluate in human immunodeficiency virus (HIV) infected patients estimated glomerular filtration rate (eGFR) trajectories during treatment with different protease inhibitors (PIs) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus tenofovir (TDF) or abacavir (ABC) and lamivudine or emtricitabine (xTC).Retrospective study of patients followed at a single clinical center; all patients who started TDF or ABC for the first time with a NNRTI or lopinavir/r (LPV/r) or atazanavir/r (ATV/r) or darunavir/r (DRV/r), for whom at least 1 eGFR value before the start and during the studied treatment was known, were included in this analysis. eGFR was calculated by means of the CKD-EPI formula. Univariate and multivariate mixed linear model (MLM) was applied to estimate eGFR slope with the considered antiretroviral treatment.In the 1658 patients treated with TDF/xTC (aged 43 [37-48] years, with an eGFR of 105 [96; 113] mL/min/1.73 m, 80% males, 92% Caucasians, 10% coinfected with HCV, 4% with diabetes, 11% with hypertension, 38% naive for antiretroviral therapy (ART), 37% with HIV-RNA <50 copies/mL) the median follow-up was 2.5 (1.2-4.6) years. Their adjusted eGFR slopes (95% CI) were -1.26 (-1.58; -0.95), -0.43 ( 1.20; +0.33), -0.86 (-1.28; -0.44), and -0.20 (-0.42; +0.02) mL/min/1.73 m per year in patients treated with ATV/r, DRV/r, LPV/r, and NNRTI, respectively. Patients receiving ATV/r or LPV/r had a greater adjusted decline in eGFR compared with those receiving NNRTIs (difference -1.06 [-1.44; -0.69] mL/min/1.73 m per year, P <0.001; and -0.66 [-1.13; -0.20] mL/min/1.73 m per year, P = 0.005, respectively); adjusted eGFR slopes were similar in patients receiving DRV/r and in those receiving NNRTIs. Patients receiving ATV/r had a greater adjusted eGFR decline than those treated with DRV/r (difference -0.83 [-1.65; -0.02] mL/min/1.73 m per year; P = 0.04), but not than those receiving LPV/r; no significant difference was observed in adjusted eGFR slopes between patients receiving DRV/r and those receiving LPV/r. In the 286 patients treated with ABC and lamivudine, eGFR slopes were similar, independent of the PI.In patients receiving TDF/xTC, eGFR trajectories were small for all regimens and declined less in patients receiving DRV/r or NNRTIs than in those treated with ATV/r or LPV/r. PMID- 27258511 TI - Effects of Low Glycemic Index Diets on Gestational Diabetes Mellitus: A Meta Analysis of Randomized Controlled Clinical Trials. AB - Studies of the effects of low glycemic index (LGI) diets on gestational diabetes mellitus (GDM) have reported conflicting findings.The aim of the study was to evaluate the results of randomized controlled trials (RCTs) that investigated the effects of LGI diets with and without added dietary fiber (DF) on maternal and neonatal outcomes in GDM patients.We searched the MEDLINE, EMBASE, EBSCO, Springer, Ovid, and Cochrane Library databases for studies of the effects of LGI diets in GDM patients. We performed a meta-analysis of the effects of the LGI diets with and without added dietary fiber (DF) on GDM outcomes. Risk ratios (RR) and 95% confidence intervals (CIs) were calculated using random- and fixed effects models.Five RCTs involving 302 participants were included in our meta analysis. No statistically significant differences in the risks of cesarean section delivery, large for gestational age, and small for gestational age were observed. The risk of macrosomia in the LGI groups was significantly lower (RR = 0.27; 95% CI: 0.10-0.71; P = 0.008) than that in the control groups. Our subgroup analysis of the effects of DF showed that LGI diets with an increased level of DF, relative to the control diet, reduced the risk of macrosomia beyond that of the LGI diets alone (RR: 0.17 vs 0.47, respectively). The subgroup analysis also showed that LGI diets in which the level of DF was approximately equivalent to that in the control diets significantly reduced the risk of insulin usage (RR = 0.69; 95% CI: 0.52-0.92; P = 0.01).The LGI diets reduced the risk of macrosomia in GDM patients, and LGI diets with added DF reduced the risk of macrosomia further. The LGI diets with levels of DF approximately equivalent to that in the control diets reduced the risk of insulin usage in GDM patients. PMID- 27258512 TI - Surgical Treatment of Crohn Colitis Involving More Than 2 Colonic Segments: Long Term Outcomes From a Single Institution. AB - The incidence of primary Crohn colitis is uncommon and surgical treatment has remained controversial, although most patients with Crohn colitis eventually require surgical intervention. This study aims to compare the operative outcomes of patients who underwent segmental versus either total colectomy or total proctocolectomy for Crohn colitis and to assess potential risk factors associated with clinical and surgical recurrence-free survivals.This is a retrospective study of 116 patients who underwent primary surgery for Crohn colitis between August 1997 and July 2011. Patients were classified based on the type of surgery: segmental colectomy (SC group; n = 71) or either total colectomy or total proctocolectomy (TC group; n = 45).There were no significant differences in postoperative complications or the nutritional state between the SC and TC groups. Patients in TC group had a significantly higher clinical recurrence-free survival (CRFS). Among the 54 patients with multisegmental Crohn colitis, the TC group had a significantly increased CRFS and surgical recurrence-free survival (SRFS), compared with patients in the SC group (5-year CRFS: 82.0% +/- 5.8% vs 22.2% +/- 13.9%, P = 0.001; 5-year SRFS: 88.1% +/- 5.0% vs 44.4% +/- 16.6%, P = 0.001). By multivariate analysis of patients with multisegments involved, SC was a risk factor for SRFS and CRFS (hazard ratio [HR] = 4.637, 95% confidence interval [CI] = 1.387-15.509, P = 0.013 and HR = 32.407, 95% CI = 2.873-365.583, P = 0.005).TC patients have significantly increased CRFS and TC in patients with multisegment involvement may affect improved SRFS and CRFS. Among patients with multisegmental Crohn colitis, SC is an independent risk factor for CRFS and SRFS. PMID- 27258513 TI - Clinical Features and Outcomes of Spontaneous Bacterial Peritonitis Caused by Streptococcus pneumoniae: A Matched Case-Control Study. AB - Streptococcus pneumoniae is a well-known cause of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. However, little information is available regarding clinical characteristics and outcomes of SBP caused by S. pneumoniae. It has been suggested that spontaneous pneumococcal peritonitis (SPP) often spreads hematogenously from concomitant pneumococcal pneumonia, and is associated with a higher rate of mortality.During the period between January 1997 and December 2013, 50 SPP cases were identified. These cases were then age/sex matched with 100 patients with SBP due to causes other than S. pneumoniae (controls).SPP accounted for 4.3% (50/1172) of all culture-proven SBPs. The baseline Child-Pugh class, etiology of cirrhosis, and model for end-stage liver disease scores were comparable for the 2 groups. SPP patients were more likely than control patients to have a community-acquired infection (90.0% vs. 76.0%; P = 0.04), concurrent bacteremia (84.0% vs. 59.0%; P = 0.002), and to present with variceal bleeding (10.0% vs. 1.0%; P = 0.02). None of the study patients had pneumococcal pneumonia. The most common initial empirical therapy for both groups was third-generation cephalosporins (96.0% vs. 91.0%; P = 0.34) which was active against a significantly higher proportion of the cases than of the controls (97.8% vs. 78.7%; P = 0.003). Thirty-day mortality was significantly lower in the case group than in the control group (10.0% vs. 24.0%; P = 0.04).SPP was not associated with pneumococcal pneumonia and showed lower mortality than SBP caused by other organisms. However, the present study was constrained by the natural limitations characteristic of a small, retrospective study. Therefore, large scale, well-controlled studies are required to demonstrate the influence of SPP on mortality, which was marginal in the present study. PMID- 27258514 TI - The Association Between Peptic Ulcer Disease and Ischemic Stroke: A Population Based Longitudinal Study. AB - Stroke is a common cause of death worldwide, but about 30% of ischemic stroke (IS) patients have no identifiable contributing risk factors. Because peptic ulcer disease (PUD) and vascular events share some common risk factors, we conducted a population-based study to evaluate the association between PUD and IS.We followed up a representative sample of 1 million residents of Taiwan using the National Health Insurance Research Database from 1997 to 2011. We defined patients who received medications for PUD and had related diagnosis codes as the PUD group, and a reference group matched by age and sex was sampled from those who did not have PUD. We also collected data on medical history and monthly income. The events of IS occurred after enrollment were compared between the 2 groups. The data were analyzed using Cox proportional hazard models at the 2 tailed significant level of 0.05.The PUD group had higher income and prevalence of hypertension, diabetes mellitus (DM), heart disease, and hyperlipidemia. They also had a higher risk of developing IS with an adjusted hazard ratio of 1.31 (95% confidence interval: 1.20-1.41). Other independent risk factors included male sex, older age, lower income, and co-morbidity of hypertension, diabetes mellitus (DM), and heart disease.PUD is a risk factor for IS, independent of conventional risk factors such as male sex, older age, lower income, and co morbidity of hypertension, DM, and heart disease. Prevention strategies taking into account PUD should be developed and evaluated. PMID- 27258516 TI - Modified Thoracoscopic Hepatectomy For Segment VIII: A Case Report. AB - Although previous studies have reported the use of total thoracoscopic hepatectomy (TH) for malignant liver tumors, it is technically impossible to perform intraoperative ultrasonography (IUSO) to exclude intrahepatic metastasis for the whole liver via a thoracic approach. Therefore, total TH may be inappropriate for these patients. We here report the first case of modified TH for a malignant liver tumor in China.The patient was a 26-year-old man with a 10 year HBV infection. Preoperative CT showed a 1.2 cm * 0.9 cm mass located in segment VIII. His alpha-fetal protein level was 444 ng/mL. Child-Pugh was Grade (A, 6), whereas an ICG-15 test yielded 2.7%. HCC was diagnosed preoperatively. The indications for TH were difficult tumor location, HCC, and a young patient with good resilience.The modified TH included 2 steps: (1) the patient was placed in a supine position. IUSO was used to locate the tumor in segment VIII and determine that intrahepatic metastasis had not occurred. The hepatoduodenal ligament was hanged over using a Pringle maneuver; (2) patient was then placed in the left-lateral position with single-lung ventilation. Three trocars were placed into the right thoracic cavity. The intra-thoracic space was observed using a regular 10-mm rigid scope. The diaphragm was transected and retracted. IUSO was used again to confirm the tumor location. Under the Pringle maneuver (once every 10 min), the superficial portion of the liver was transected by ultrasonic shears, whereas the deeper tissue was transected by LigaSure. Bipolar was used for hemostasis. The specimen was put into a retrieval bag and removed from the abdominal trocar. The diaphragm was repaired by running suturing. The operation time was 260 minutes and estimated blood loss was 30 mL. The patient was discharged on postoperative day 5 with normal liver function. No complications arose.Total TH may be inappropriate for malignant liver tumors due to the limitation of IUSO for the whole liver. The 2-step modified TH is technically feasible and suitable for malignant liver tumors located in segments VII or VIII.Video abstract: http://links.lww.com/MD/B6. PMID- 27258517 TI - Hepatitis B Virus Infection Is a Risk Factor for Periprosthetic Joint Infection Among Males After Total Knee Arthroplasty: A Taiwanese Nationwide Population Based Study. AB - Periprosthetic joint infection (PJI) is a grave complication that can affect patients undergoing total knee arthroplasty (TKA). In this study, we aim to determine whether hepatitis B virus (HBV) infection is a risk factor for PJIs.All patients (1184 males, 3435 females) undergoing primary TKA in Taiwan from 2001 to 2010 were recruited for analysis.The incidence of PJI was 523 among the males with HBV infection and 110 among the males without HBV (per 10,000 person-years, P < 0.001). The males with HBV infection had a 4.32-fold risk of PJI compared with the males without HBV. HBV infection and diabetes were the risk factors for PJI among males. The incidence of PJI was 58.8 among the females with HBV infection and 75.2 among the females without HBV (per 10,000 person-years, P = 0.67). The risk of PJI was higher for the males with HBV infection than for the males without 0.5 to 1 year after TKA (hazard ratio [HR] = 18.7, 95% confidence interval (CI) = 1.90-184) and >1 year after TKA (HR = 4.80, 95% CI = 1.57 14.7).HBV infection is a risk factor for PJI after TKA among males. PMID- 27258515 TI - Safety and Efficacy of Endoscopic Therapy for Nonmalignant Duodenal Duplication Cysts: Case Report and Comprehensive Review of 28 Cases Reported in the Literature. AB - Analyze efficacy, safety of endoscopic therapy for duodenal duplication cysts (DDC) by comprehensively reviewing case reports.Tandem, independent, systematic, computerized, literature searches were performed via PubMed using medical subject headings or Keywords "cyst" and "duodenal" and "duplication"; or "cyst", and "endoscopy" or "endoscopic", and "therapy" or "decompression"; with reconciliation of generated references by two experts. Case report followed CARE guidelines.Literature review revealed 28 cases (mean = 1.3 +/- 1.2 cases/report). Endoscopic therapy is increasingly reported recently (1984-1999: 3 cases, 2000 2015: 25 cases, P = 0.003, OR = 8.33, 95%-CI: 1.77-44.5). Fourteen (54%) of 26 patients were men (unknown-sex = 2). Mean age = 32.2 +/- 18.3 years old. Procedure indications: acute pancreatitis-16, abdominal pain-8, jaundice-2, gastrointestinal (GI) obstruction-1, asymptomatic cyst-1. Mean maximal DDC dimension = 3.20 +/- 1.53 cm (range, 1-6.5 cm). Endoscopic techniques included cyst puncture via needle knife papillotomy (NKP)/papillotome-18, snare resection of cyst-7, cystotome-2, and cyst needle aspiration/ligation-1. Endoscopic therapy was successful in all cases. Among 24 initially symptomatic patients, all remained asymptomatic post-therapy without relapses (mean follow-up = 36.5 +/- 48.6 months, 3 others reported asymptomatic at follow-up of unknown duration; 1 initially asymptomatic patient remained asymptomatic 3 years post-therapy). Two complications occurred: mild intraprocedural duodenal bleeding related to NKP and treated locally endoscopically.A patient is reported who presented with vomiting, 15-kg-weight-loss, and profound dehydration for 1 month from extrinsic compression of duodenum by 14 * 6 cm DDC, underwent successful endosonographic cyst decompression with large fenestration of cyst and endoscopic aspiration of 1 L of fluid from cyst with rapid relief of symptoms. At endoscopy the DDC was intubated and visualized and random endoscopic mucosal biopsies were obtained to help exclude malignant or dysplastic DDC.Study limitations include retrospective literature review, potential reporting bias, limited patient number, variable follow-up.In conclusion, endoscopic therapy for DDC was efficacious in all 29 reported patients including current case, including patients presenting acutely with acute pancreatitis, or GI obstruction. Complications were rare and minor, suggesting that endoscopic therapy may be a useful alternative to surgery for nonmalignant DDC when performed by expert endoscopists. PMID- 27258518 TI - A Case Report of Local Recurrence Developing 24 Years After Mastectomy for Breast Cancer Recurrence From Breast Cancer After 24 Years. AB - INTRODUCTION: Breast cancer is a commonly diagnosed cancer, in which most patients' metastases (about 75%) occurred in 5 years after the initial diagnosis, especially in 3 years. Recrudescence exceeding 20 years is rarely reported in the past several decades.Case information: A 68-year-old female patient presented with breast cancer in which 3 focal increased 18F-fluorodeoxyglucose uptake in the right supraclavicular lymph node, the mediastinum and sternum were found on positron emission tomography and computed tomography. Then we learned that the patient had suffered from breast cancer and been given a right-sided mastectomy 24 years ago. Histopathology from the mediastinum revealed metastatic, moderately differentiated breast adenomatous cell carcinoma. CONCLUSION: We report this late recurrence of breast cancer 24 years following mastectomy, suggesting that possible recurrence of this disease with a 24-year latency period should be taken into consideration. PMID- 27258519 TI - Higher Daily Physical Activities Continue to Preserve Muscle Strength After Mid Life, But Not Muscle Mass After Age of 75. AB - The objective of this study is to explore the impact of aging and daily physical activities (PA) on muscle mass and muscle strength among community-dwelling people in Taiwan.The design is a cross-sectional study. Setting is a population based community study.One thousand eight hundred thirty-nine community-dwelling people aged 50 years and older in Taiwan participated in the study.Measurements include demographic characteristics, Charlson Comorbidity Index (CCI) for multimorbidity, mini-nutritional assessment (MNA) for nutritional evaluation, functional autonomy measurement system (SMAF) for functional capacity, Chinese version mini mental state examination (MMSE), 5-item Taiwan Geriatric Depression Scale (TGDS-5), Chinese version of International Physical Activity Questionnaire (IPAQ), height-adjusted skeletal muscle index (SMI) by dual-energy X-ray absorptiometry, handgrip strength, timed 6-m walking test for usual gait speed. Laboratory measurements include testosterone, sex-hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), high-sensitivity C-reactive protein (hsCRP), 25-OH vitamin D, and insulin resistance.After adjusted for age, the lowest PA tertile was associated with multimorbidity, poorer functional capacity and nutritional status, more depressive symptoms, lower SMI and lower handgrip strength, and lower free androgen index (FAI) in men. The negative association between PA and low SMI was more significant among subjects aged younger than 65 and the association decreased with older age. For subjects aged younger than 65, moderate daily PA (Q2) group had lower risk of low SMI compared with Q1 participants (OR: 0.62, 95% CI = 0.39-0.98, P = 0.040). For muscle strength, higher daily PA was associated with lower risk of low handgrip strength after age of 65 and the effect was dose dependent. The effect was attenuated by potential confounders during age 65 to 74, while after age 75, the result was almost unchanged in fully adjusted model (OR = 0.37, 95% CI = 0.18-0.79, P = 0.010).Older age may attenuate the protective effects of higher daily PA on preventing muscle loss, but higher daily PA continues to preserve muscle strength at different age groups, even after the age of 75. The prognostic role of daily PA may be mediated by muscle strength instead of muscle mass among people aged 75 years and older. PMID- 27258520 TI - Does Breast Magnetic Resonance Imaging Combined With Conventional Imaging Modalities Decrease the Rates of Surgical Margin Involvement and Reoperation?: A Case-Control Comparative Analysis. AB - The objective of this study was to assess whether preoperative breast magnetic resonance imaging (MRI) combined with conventional breast imaging techniques decreases the rates of margin involvement and reexcision.Data on patients who underwent surgery for primary operable breast cancer were obtained from the Changhua Christian Hospital (CCH) breast cancer database. The rate of surgical margin involvement and the rate of reoperation were compared between patients who underwent conventional breast imaging modalities (Group A: mammography and sonography) and those who received breast MRI in addition to conventional imaging (Group B: mammography, sonography, and MRI).A total of 1468 patients were enrolled in this study. Among the 733 patients in Group A, 377 (51.4%) received breast-conserving surgery (BCS) and 356 (48.6%) received mastectomy. Among the 735 patients in Group B, 348 (47.3%) received BCS and 387 (52.7%) received mastectomy. There were no significant differences in operative method between patients who received conventional imaging alone and those that received MRI and conventional imaging (P = 0.13). The rate of detection of pathological multifocal/multicentric breast cancer was markedly higher in patients who received preoperative MRI than in those who underwent conventional imaging alone (14.3% vs 8.6%, P < 0.01). The overall rate of surgical margin involvement was significantly lower in patients who received MRI (5.0%) than in those who received conventional imaging alone (9.0%) (P < 0.01). However, a significant reduction in rate of surgical margin positivity was only observed in patients who received BCS (Group A, 14.6%; Group B, 6.6%, P < 0.01). The overall BCS reoperation rates were 11.7% in the conventional imaging group and 3.2% in the combined MRI group (P < 0.01). There were no significant differences in rate of residual cancer in specimens obtained during reoperation between the 2 preoperative imaging groups (Group A, 50%; Group B, 81.8%, P = 0.09). In multivariate analysis, multifocal/multicentric breast cancer (odds ratio = 2.38, P = 0.02) and without MRI use (odds ratio = 2.35, P < 0.01) were the major predisposing factors to margin involvement in patients received BCS.Preoperative breast MRI combined with conventional breast imaging results in a lower rate of surgical margin involvement and reoperations in patients who receive BCS. PMID- 27258521 TI - Comprehensive Circular RNA Profiling Reveals That hsa_circ_0005075, a New Circular RNA Biomarker, Is Involved in Hepatocellular Crcinoma Development. AB - There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development; however, their role in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to determine the circRNA expression profile in HCC, and investigate relevant mechanisms for cancer progression. The global circRNA expression profile between HCC (n = 3) and adjacent normal liver (n = 3) tissue was significantly different. Three circRNAs (hsa_circ_0000520, hsa_circ_0005075, and hsa_circ_0066444) showed significantly different expression levels in HCC tissues, which were further validated in 60 matched tissue samples using real time qRT-PCR. Only hsa_circ_0005075 exhibited significant difference in expression (P <0.001) between HCC and normal tissues. Hsa_circ_0005075 expression correlated with HCC tumor size (P = 0.042), and showed good diagnostic potential (AUROC = 0.94). Finally, we constructed a network of hsa_circ_0005075-targeted miRNA-gene interactions, including miR-23b-5p, miR-93-3p, miR-581, miR-23a-5p, and their corresponding mRNAs. Gene oncology analysis revealed that hsa_circ_0005075 could participate in cell adhesion during HCC development. In summary, we identified hsa_circ_0005075 as a potential HCC biomarker; however, further studies are required to confirm the role of this circRNA, and others, in HCC development. PMID- 27258522 TI - Minimally Invasive Colorectal Cancer Surgery in Europe: Implementation and Outcomes. AB - Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse.In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders.The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63-0.69), Sweden (HR 0.68, 95% CI 0.60-0.76), and Norway (HR 0.73, 95% CI 0.67-0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68 0.80) and Sweden (HR 0.77, 95% CI 0.66-0.90).Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients. PMID- 27258523 TI - Risk of Tuberculosis Among Patients on Dialysis: The Predictive Value of Serial Interferon-Gamma Release Assay. AB - Patients on long-term dialysis are at high risk for tuberculosis (TB). Although latent tuberculosis infection (LTBI) is good target for TB eradication, interferon-gamma release assay-defined LTBI has a high proportion of negative conversion and lacks active TB correlation among patients on dialysis.Patients on long-term dialysis were screened in multiple centers in Taiwan. QuantiFERON-TB Gold In-tube (QFT-GIT) was used to define LTBI and was performed thrice at 6 month intervals. The primary outcome was active TB diagnosed after LTBI screening. The incidence and predictive value of QFT-GIT were analyzed.The 940 dialysis patients enrolled had an average age of 59.3 years. The initial QFT-GIT results were positive in 193, including 49.6% with persistent positive results on second check. In an average follow-up period of 3 years, 7 patients had TB. Three (319.1 per 100,000 person-yrs) and 4 (141.8 per 100,000 person-yrs) of them were prevalent and incident TB cases, respectively. Persistent positive QFT-GIT for 2 and 3 times correlated with increased hazard ratio for TB (14.44 and 20.29, respectively) compared with a single positive result (hazard ratio 10.38). Among those with 3 positive QFT-GIT results, TB development rate was 4.5% and incidence rate was 1352.3 per 100,000 person-years. In contrast, none of the incident TB occurred in those with initial positive and then negative conversion of QFT GIT.In an area of intermediate TB incidence, dialysis patients have high TB risk. LTBI status is a good predictor of TB development, especially for those with more than 1 positive result. After excluding prevalent TB cases, serial follow-up of LTBI may narrow the target population to reduce treatment costs. PMID- 27258524 TI - Effects of Intraoperative Dexmedetomidine on Postoperative Pain in Highly Nicotine-Dependent Patients After Thoracic Surgery: A Prospective, Randomized, Controlled Trial. AB - To investigate the effects of intraoperative dexmedetomidine on pain in highly nicotine-dependent patients after thoracic surgery.Highly nicotine-dependent men underwent thoracic surgery and received postoperative patient-controlled intravenous analgesia with sufentanil. In dexmedetomidine group (experimental group, n = 46), dexmedetomidine was given at a loading dose of 1 MUg/kg for 10 minutes, followed by continuous infusion at 0.5 MUg/kg/h until 30 minutes before the end of surgery. The saline group (control group, n = 48) received the same volume of saline. General anesthesia was administered via a combination of inhalation and intravenous anesthetics. If necessary, patients were administered a loading dose of sufentanil by an anesthesiologist immediately after surgery (0 hours). Patient-controlled analgesia was started when the patient's resting numerical rating scale (NRS) score was less than 4. Resting and coughing NRS scores and sufentanil dosage were recorded 0, 1, 4 hours, and every 4 hours until 48 hours after surgery. Dosages of other rescue analgesics were converted to the sufentanil dosage. Surgical data, adverse effects, and degree of satisfaction were obtained.Cumulative sufentanil dosage, resting NRS, and coughing NRS in the first 24 hours after surgery and heart rate were lower in the experimental compared with the control group (P <0.05). No patient experienced sedation or respiratory depression. Frequency of nausea and vomiting and degree of satisfaction were similar in both groups.Intraoperative dexmedetomidine was associated with reduced resting and coughing NRS scores and a sufentanil-sparing effect during the first 24 hours after thoracic surgery. PMID- 27258525 TI - Depression and Insomnia in Patients With Psoriasis and Psoriatic Arthritis Taking Tumor Necrosis Factor Antagonists. AB - Psoriasis patients with moderate to severe disease often present with depression and insomnia. Treatment targeting both psoriasis and psychological comorbidities is needed to improve the quality of life of these patients.In this nationwide cohort study, a total of 980 patients with psoriatic arthritis or psoriasis who had received nonbiological disease-modifying antirheumatic drugs and biologics therapy between 2009 and 2012 were identified. The prevalence rates of patients taking medications for depression and insomnia were compared before and after biologics therapy. Logistic regression method was used to investigate the risk factors for depression and insomnia. Further stratified analyses were performed to examine the prevalence of use of medications for depression and insomnia among different patient subgroups.The prevalence of patients taking regular antidepressants before starting biologics therapy was about 20%. There was a more than 40% reduction in this prevalence after biologics therapy for 2 years. Age higher than 45 years, female sex, presence of comorbidities, and psoriatic arthritis were independently associated with depression and insomnia. Further stratified analyses revealed a more rapid and significant reduction in depression/insomnia in those undergoing continuous biologics therapy, younger than 45 years, without psoriatic arthritis and not taking concomitant methotrexate, when compared with their counterparts.The results suggest that biologics therapy may be associated with reduced rates of depression and insomnia, and a reduced rate of regular antidepressants use in psoriasis patients. PMID- 27258526 TI - Pregnancy in Budd-Chiari Syndrome: Case Report and Proposed Risk Score. AB - Due to its rarity, experience with pregnancy in Budd-Chiari syndrome (BCS) is limited. With the advent of new treatment modalities, transjugular intrahepatic portosystemic shunt in particular, numbers of affected women seeking pregnancy with BCS are expected to rise. Here, we use a case that ended lethal within 2 years after delivery to discuss the effect of pregnancy on BCS and vice versa, and to highlight the necessity of a multidisciplinary teamwork. Additionally, a risk classification is proposed which may serve as a framework for preconception counseling and assist in the establishment and evaluation of treatment algorithms; its criteria need to be defined and assessed for their applicability in further studies. PMID- 27258528 TI - Risk Factors of Submucosal or Lymphovascular Invasion in Early Gastric Cancer <2 cm. AB - Although prediction of submucosal (SM) or lymphovascular (LV) invasion is important before endoscopic resection of early gastric cancer (EGC), it can only be confirmed following endoscopic resection. After endoscopic resection, patients with SM or LV invasion may require additional surgery due to high risk of lymph node metastasis.We conducted a retrospective study to identify risk factors for SM or LV invasion before endoscopic submucosal dissection (ESD) of EGC. Between January 2009 and May 2014, we reviewed the data of patients with EGC who met the absolute indications for ESD before procedure: well and/or moderately differentiated adenocarcinomas, tumors <= 2 cm in length and absence of ulcer or ulcer-scar.During study period, a total of 308 lesions in 297 patients were included. SM or LV invasion was detected in 34 lesions (34/308, 11.0%). Multivariate analysis revealed that a moderately differentiated adenocarcinoma (odds ratio [OR] 4.157, P = 0.000) and location of the stomach (the upper and middle third; OR 3.100, P = 0.008) were significant risk factors for SM or LV invasion.Careful consideration of endoscopic treatment decision might be necessary for the patients with a moderately differentiated adenocarcinoma and EGC located on the upper and middle third of the stomach. PMID- 27258527 TI - Assessment of Lung Recruitment by Electrical Impedance Tomography and Oxygenation in ARDS Patients. AB - We hypothesized that not all patients with appreciably recruited lung tissue during a recruitment maneuver (RM) show significant improvement of oxygenation. In the present study, we combined electrical impedance tomography (EIT) with oxygenation measurements to examine the discrepancies of lung ventilation and perfusion versus oxygenation after RM.A 2-minute RM (20 cm H2O positive end expiratory pressure [PEEP] + 20 cm H2O pressure control) was prospectively conducted in 20 acute respiratory distress syndrome patients from January 2014 to December 2014. A decremental PEEP trial was performed to select the PEEP level after RM. A positive response to RM was identified as PaO2 + PaCO2 >=400 mm Hg. Relative differences in the distribution of ventilation and perfusion in the most dependent region of interest (ROI4) were monitored with EIT and denoted as the ventilation-perfusion index.Ten patients were found to be responders and 10 patients to be nonresponders. No significant difference in baseline PaO2/FiO2 was observed between nonresponders and responders. A significantly higher PaO2/FiO2 ratio during RM and higher PEEP set after PEEP titration were recorded in responders. In both responders and nonresponders, the proportion of ventilation distributed in ROI4 compared with the global value was lower than the cardiac related activity before RM, but this situation was reversed after RM (P < 0.01 in each group). Six out of 10 nonresponders exhibited a remarkable increase in ventilation in ROI4. A significant difference in the relative ventilation perfusion index was found between the patients with remarkable and insufficient lung tissue reopening in the nonresponder group (P < 0.01).A discrepancy between lung tissue reopening and oxygenation improvement after RM was observed. EIT has the potential to evaluate the efficacy of RM by combining oxygenation measurements. PMID- 27258529 TI - Outcomes of 50 Patients With Ewing Sarcoma Family of Tumors Treated at a Single Institution in Taiwan. AB - To identify the prognostic factors and long-term outcome of the Ewing sarcoma family of tumors (ESFT), data on 50 patients with ESFT treated at Taipei Veterans General Hospital between February 1991 and March 2014 were retrospectively considered. The influence of patient demographics, tumor features, and clinical and therapeutic parameters on overall survival (OS) and progression-free survival (PFS) rates were assessed. The results revealed that 21 of the 50 patients (42%) were metastatic at diagnosis. The median follow-up time was 1.8 years. The 5-year OS and PFS for patients who were nonmetastatic were 61.6% and 55.5%, respectively, and 18.8% and 15.4% for patients who were metastatic, respectively. The key adverse prognostic factor was metastasis at diagnosis. Radiotherapy for local control was associated with improved PFS. The high rate of primary metastasis and poorer outcomes of nonmetastatic ESFT compared with results from Western studies, along with previously reported low rates of ESFT in Taiwanese people, suggest that genetic factors play a role in the pathogenesis of ESFT and chemotherapy pharmacokinetics and pharmacodynamics. Radiotherapy in local treatment should be considered more aggressively in Taiwanese patients with ESFT. PMID- 27258531 TI - A Shape-Persistent Cryptand for Capturing Polycyclic Aromatic Hydrocarbons. AB - A shape-persistent cryptand 1, containing two face-to-face oriented electron deficient 2,4,6-triphenyl-1,3,5-triazine units separated by approximately 7 A, and bridged by two rigid 1,8-naphthyridine linkers and a pentaethylene oxide loop, is created for capturing polycyclic aromatic hydrocarbons. Cryptand 1 formed 1:1 complexes with PAH guest molecules, such as phenanthrene (6), anthracene (7), pyrene (8), triphenylene (9), and tetraphene (10). The single crystal structure of complex 6?1 revealed that 6 was included in the cavity of 1 via face-to-face pi...pi stacking interactions. Soaking crystalline 1 in a toluene solution of anthracene resulted in anthracene from the toluene solution being picked up by the crystalline solid of 1. PMID- 27258530 TI - Adaptation and Latent Structure of the Swahili Version of Beck Depression Inventory-II in a Low Literacy Population in the Context of HIV. AB - OBJECTIVE: We set out to adapt the Beck Depression Inventory (BDI)-II in Kenya and examine its factorial structure. METHODS: In the first phase we carried out in-depth interviews involving 29 adult members of the community to elicit their understanding of depression and identify aspects of the BDI-II that required adaptation. In the second phase, a modified version of BDI-II was administered to 221 adults randomly selected from the community to allow for the evaluation of its psychometric properties. In the third phase of the study we evaluated the discriminative validity of BDI-11 by comparing a randomly chosen community sample (n = 29) with caregivers of adolescents affected by HIV (n = 77). RESULTS: A considerable overlap between the BDI symptoms and those generated in the interviews was observed. Relevant idioms and symptoms such as 'thinking too much' and 'Kuchoka moyo (having a tired heart)' were identified. The administration of the BDI had to be modified to make it suitable for the low literacy levels of our participants. Fit indices for several models (one factorial, two-factor model and a three factor model) were all within acceptable range. Evidence indicated that while multidimensional models could be fitted, the strong correlations between the factors implied that a single factor model may be the best suited solution (alpha [0.89], and a significant correlation with locally identified items [r = 0.51]) confirmed the good psychometric properties of the adapted BDI-II. No evidence was found to support the hypothesis that somatization was more prevalent. Lastly, caregivers of HIV affected adolescents had significantly higher scores compared to adults randomly selected from the community F(1, 121) = 23.31, p < .001 indicating the discriminative validity of the adapted BDI = II. CONCLUSIONS: With an adapted administration procedure, the BDI-II provides an adequate measure of depressive symptoms which can be used alongside other measures for proper diagnosis in a low literacy population. PMID- 27258532 TI - Bacterial Community Diversity Harboured by Interacting Species. AB - All animals are infected by microbial partners that can be passengers or residents and influence many biological traits of their hosts. Even if important factors that structure the composition and abundance of microbial communities within and among host individuals have been recently described, such as diet, developmental stage or phylogeny, few studies have conducted cross-taxonomic comparisons, especially on host species related by trophic relationships. Here, we describe and compare the microbial communities associated with the cabbage root fly Delia radicum and its three major parasitoids: the two staphylinid beetles Aleochara bilineata and A. bipustulata and the hymenopteran parasitoid Trybliographa rapae. For each species, two populations from Western France were sampled and microbial communities were described through culture independent methods (454 pyrosequencing). Each sample harbored at least 59 to 261 different bacterial phylotypes but was strongly dominated by one or two. Microbial communities differed markedly in terms of composition and abundance, being mainly influenced by phylogenetic proximity but also geography to a minor extent. Surprisingly, despite their strong trophic interaction, parasitoids shared a very low proportion of microbial partners with their insect host. Three vertically transmitted symbionts from the genus Wolbachia, Rickettsia, and Spiroplasma were found in this study. Among them, Wolbachia and Spiroplasma were found in both the cabbage fly and at least one of its parasitoids, which could result from horizontal transfers through trophic interactions. Phylogenetic analysis showed that this hypothesis may explain some but not all cases. More work is needed to understand the dynamics of symbiotic associations within trophic network and the effect of these bacterial communities on the fitness of their hosts. PMID- 27258534 TI - Assessing hemodynamics noninvasively in patients with heart failure. AB - PURPOSE OF REVIEW: Describe the contemporary assessment of cardiac hemodynamics using a comprehensive echo-Doppler examination in the heart failure (HF) patient. RECENT FINDINGS: Cardiac flow and filling pressures, on both the left and right sides of the heart, are fundamental to the accurate assessment of the HF patient. Accurate assessment of left ventricular (LV) and right ventricular (RV) systolic and diastolic function is necessary to establish, or exclude, HF as a cause or component of dyspnea in a given patient and to help determine causes of hemodynamic instability in HF patients. Variables such as spectral Doppler (mitral and tricuspid inflow, pulmonary and hepatic venous flow, and pulmonary valve regurgitation signal), tissue Doppler imaging, and speckle tracking, applied to the left and right heart, can help to accurately estimate cardiac hemodynamics. SUMMARY: A comprehensive echocardiogram with Doppler can provide an accurate assessment of left and right heart hemodynamics that is fundamental to the assessment and management of the HF patient. PMID- 27258533 TI - Exercise for Individuals with Lewy Body Dementia: A Systematic Review. AB - BACKGROUND: Individuals with Lewy body Dementia (LBD), which encompasses both Parkinson disease dementia (PDD) and Dementia with Lewy Bodies (DLB) experience functional decline through Parkinsonism and sedentariness exacerbated by motor, psychiatric and cognitive symptoms. Exercise may improve functional outcomes in Parkinson's disease (PD), and Alzheimer's disease (AD). However, the multi-domain nature of the LBD cluster of symptoms (physical, cognitive, psychiatric, autonomic) results in vulnerable individuals often being excluded from exercise studies evaluating physical function in PD or cognitive function in dementia to avoid confounding results. This review evaluated existing literature reporting the effects of exercise interventions or physical activity (PA) exposure on cluster symptoms in LBD. METHODS: A high-sensitivity search was executed across 19 databases. Full-length articles of any language and quality, published or unpublished, that analysed effects of isolated exercise/physical activity on indicative Dementia with Lewy Bodies or PD-dementia cohorts were evaluated for outcomes inclusive of physical, cognitive, psychiatric, physiological and quality of life measures. The protocol for this review (Reg. #: CRD42015019002) is accessible at http://www.crd.york.ac.uk/PROSPERO/. RESULTS: 111,485 articles were initially retrieved; 288 full articles were reviewed and 89.6% subsequently deemed ineligible due to exclusion of participants with co-existence of dementia and Parkinsonism. Five studies (1 uncontrolled trial, 1 randomized controlled trial and 3 case reports) evaluating 16 participants were included. Interventions were diverse and outcome homogeneity was low. Habitual gait speed outcomes were measured in 13 participants and increased (0.18m/s, 95% CI -0.02, 0.38m/s), exceeding moderate important change (0.14m/s) for PD cohorts. Other outcomes appeared to improve modestly in most participants. DISCUSSION: Scarce research investigating exercise in LBD exists. This review confirms exercise studies in PD and dementia consistently exclude LBD participants. Results in this cohort must be treated with caution until robustly designed, larger studies are commissioned to explore exercise efficacy, feasibility and clinical relevance. PMID- 27258535 TI - Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation. AB - BACKGROUND & AIMS: Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. METHODS: We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. RESULTS: The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P < 0.001). In multivariate analysis, renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P < 0.0001). Importantly, the impact of renal failure was less marked in patients with ALD (HR = 1.31, P < 0.0001) than in patients with NASH (HR = 1.73, P < 0.0001) or HCV (HR = 1.52, P < 0.0001). Despite a higher model for end-stage liver disease (MELD) score at the time of LT, ALD patients with renal failure had better long-term prognosis than non-ALD patients. CONCLUSIONS: Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT. PMID- 27258536 TI - Amino Acid and Secondary Metabolite Production in Embryogenic and Non-Embryogenic Callus of Fingerroot Ginger (Boesenbergia rotunda). AB - Interest in the medicinal properties of secondary metabolites of Boesenbergia rotunda (fingerroot ginger) has led to investigations into tissue culture of this plant. In this study, we profiled its primary and secondary metabolites, as well as hormones of embryogenic and non-embryogenic (dry and watery) callus and shoot base, Ultra Performance Liquid Chromatography-Mass Spectrometry together with histological characterization. Metabolite profiling showed relatively higher levels of glutamine, arginine and lysine in embryogenic callus than in dry and watery calli, while shoot base tissue showed an intermediate level of primary metabolites. For the five secondary metabolites analyzed (ie. panduratin, pinocembrin, pinostrobin, cardamonin and alpinetin), shoot base had the highest concentrations, followed by watery, dry and embryogenic calli. Furthermore, intracellular auxin levels were found to decrease from dry to watery calli, followed by shoot base and finally embryogenic calli. Our morphological observations showed the presence of fibrils on the cell surface of embryogenic callus while diphenylboric acid 2-aminoethylester staining indicated the presence of flavonoids in both dry and embryogenic calli. Periodic acid-Schiff staining showed that shoot base and dry and embryogenic calli contained starch reserves while none were found in watery callus. This study identified several primary metabolites that could be used as markers of embryogenic cells in B. rotunda, while secondary metabolite analysis indicated that biosynthesis pathways of these important metabolites may not be active in callus and embryogenic tissue. PMID- 27258537 TI - Rapid Ethical Assessment on Informed Consent Content and Procedure in Hintalo Wajirat, Northern Ethiopia: A Qualitative Study. AB - BACKGROUND: Informed consent is a key component of bio-medical research involving human participants. However, obtaining informed consent is challenging in low literacy and resource limited settings. Rapid Ethical Assessment (REA) can be used to contextualize and simplify consent information within a given study community. The current study aimed to explore the effects of social, cultural, and religious factors during informed consent process on a proposed HPV-serotype prevalence study. METHODOLOGY: A qualitative community-based REA was conducted in Adigudom and Mynebri Kebeles, Northern Ethiopia, from July to August 2013. Data were collected by a multi-disciplinary team using open ended questions concerning informed consent components in relation to the parent study. The team conducted one-to-one In-Depth Interviews (IDI) and Focus Group Discussions (FGDs) with key informants and community members to collect data based on the themes of the study. Tape recorded data were transcribed in Tigrigna and then translated into English. Data were categorized and thematically analyzed using open coding and content analysis based on pre-defined themes. RESULTS: The REA study revealed a number of socio-cultural issues relevant to the proposed study. Low community awareness about health research, participant rights and cervical cancer were documented. Giving a vaginal sample for testing was considered to be highly embarrassing, whereas giving a blood sample made participants worry that they might be given a result without the possibility of treatment. Verbal consent was preferred to written consent for the proposed study. CONCLUSION: This rapid ethical assessment disclosed important socio-cultural issues which might act as barriers to informed decision making. The findings were important for contextual modification of the Information Sheet, and to guide the best consent process for the proposed study. Both are likely to have enabled participants to understand the informed consent better and consequently to comply with the study. PMID- 27258538 TI - MESECTODERMAL LEIOMYOMA OF THE CILIARY BODY PRESENTING AS ANTERIOR STAPHYOMA. AB - PURPOSE: To report two cases of mesectodermal leiomyoma of the ciliary body presenting as anterior staphyloma. METHODS: Two case reports with cytopathologic correlation. RESULTS: First patient (15-year-old boy) presented with a nodular lesion in the sclera. Second patient (31-year-old woman) was found to have a brown ciliary body mass. Growth of the lesion and extrascleral extension was noticed after several years of follow-up. Ultrasonography, light microscopy, and immunohistochemistry of both cases are described confirming mesectodermal leiomyoma of the ciliary body. CONCLUSION: Mesectodermal leiomyoma, despite its rarity, should be considered in the differential diagnosis of uveal tract tumors. Clinically, the diagnosis is difficult and histopathological and immunohistochemical assesment is necessary to avoid inappropriate diagnosis and erroneous treatment. PMID- 27258539 TI - SPONTANEOUS CLOSURE OF MACULAR HOLE AFTER DRAINAGE OF SUBFOVEAL PERFLUOROCARBON LIQUID. AB - PURPOSE: To report a rare case of macular hole formation after drainage of subretinal perfluorocarbon liquid (PFCL), which closed spontaneously. METHODS: Retrospective case report. A 60-year-old was noted to have subfoveal PFCL after a macula-involving retinal detachment repair with silicone oil tamponade. Spectral domain optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany) was used for postoperative imaging. RESULTS: Two months postdetachment repair, the patient underwent removal of silicone oil and drainage of subfoveal PFCL using a 41-gauge cannula through a extrafoveal retinotomy. A full-thickness macular hole was noted 2 weeks postoperatively. This closed spontaneously 4 months later, with an improvement in vision, although there was evidence of subfoveal atrophy. CONCLUSION: Macular hole formation can occur after drainage of subfoveal PFCL, with a favorable prognosis if managed conservatively. The resultant foveal atrophy highlights the importance of early identification and removal of subretinal PFCL. PMID- 27258540 TI - EN FACE IMAGING OF RETINAL ARTERY MACROANEURYSMS USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY. AB - PURPOSE: To describe the advantages of en face view with swept-source optical coherence tomography in assessing the morphologic features of retinal arterial macroaneurysms, their consequences on adjacent retina, planning laser treatment, and evaluating its effects. METHODS: Three eyes were treated for retinal arterial macroaneurysms and followed by swept-source optical coherence tomography in 2014 2015. En face images of the retina and choroid were obtained by EnView, a swept source optical coherence tomography program. RESULTS: Retinal arterial macroaneurysms have a typical optical coherence tomography appearance. En face view allows delineation of the macroaneurysm wall, thrombotic components within the dilation, and lumen measurement. Hemorrhage, lipids, and fluids can be precisely described in terms of amount and extent over the macula and depth. This technique is also practical for planning focal laser treatment and determining its effects. CONCLUSION: En face swept-source optical coherence tomography is a rapid, noninvasive, high-resolution, promising technology, which allows excellent visualization of retinal arterial macroaneurysms and their consequences on surrounding tissues. It could make angiography with intravenous injection redundant in planning and assessing therapy. PMID- 27258541 TI - TATTOO-ASSOCIATED UVEITIS WITH CHOROIDAL GRANULOMA: A RARE PRESENTATION OF SYSTEMIC SARCOIDOSIS. AB - PURPOSE: The authors report a rare case of systemic sarcoidosis manifesting as bilateral granulomatous panuveitis and multiple tattoo granulomas. METHODS: Case report. RESULTS: A 30-year-old man presented with headaches, ocular pain, photophobia, and blurred vision. He was found to have significant skin inflammation, predominantly involving areas of tattoos. Fundoscopic examination revealed bilateral granulomatous panuveitis with small focal choroidal lesions. Skin biopsy demonstrated granulomatous inflammation of the dermis with tattoo pigment evident in numerous histiocytes. He was diagnosed with systemic sarcoidosis. CONCLUSION: The authors report another rare case of tattoo associated uveitis, in which inflammation is limited to tattooed skin and the uvea. This uncommon presentation may prove informative in elucidating the pathogenesis of systemic sarcoidosis. PMID- 27258542 TI - BARTONELLA QUINTANA-ASSOCIATED NEURORETINITIS: LONGITUDINAL SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHIC FINDINGS. AB - PURPOSE: To report an unusual case of neuroretinitis caused by Bartonella quintana and its spectral-domain optical coherence tomographic (SD-OCT) features. METHODS: A 12-year-old girl presented with unilateral neuroretinitis with stellate maculopathy. Bartonellosis was confirmed after serologic testing for antibodies to B. quintana. RESULTS: Color photograph of the right eye revealed papillitis and stellate macular exudation. spectral-domain optical coherence tomography of the right eye revealed hyperreflective dots in the outer nuclear and outer plexiform layers, as well as disruption and loss of the external limiting membrane, ellipsoid zone, and interdigitation zone in the foveal area. CONCLUSION: The authors report an unusual case of neuroretinitis by B. quintana and its spectral-domain optical coherence tomographic findings. PMID- 27258543 TI - CANDIDA ENDOPHTHALMITIS FROM THE REACTIVATION OF A DORMANT LENTICULAR FUNGAL ABSCESS IN A PREMATURE INFANT. AB - BACKGROUND/PURPOSE: To report a case of fungal endophthalmitis from reactivation of a dormant lenticular fungal abscess in a severely premature infant. METHODS: Single retrospective case report. RESULTS: A female born at 23 and 6/7 weeks and weighing 620 g was diagnosed at age 29 weeks post menstrual age with persistent tunica vasculosa lentis, lenticular opacity, and aggressive posterior retinopathy of prematurity, and received bilateral intravitreal injection of bevacizumab. At the time of injection she was receiving systemic antibiotics for sepsis and fungemia. The retinopathy of prematurity regressed, as did the tunica vasculosa lentis, but a small plaque remained on the lens. At 5.5 months of age, patient presented with hypopyon and elevated intraocular pressure. Culture of intraocular fluid demonstrated Candida albicans. CONCLUSION: Candida lenticular abscess is a rare complication of systemic fungemia in premature infants. Bevacizumab-induced regression of tunica vasculosa lentis may have decreased the ability of systemically administered antifungal medications to reach the colonized lens. PMID- 27258545 TI - The genetic burden of inflammatory bowel diseases: implications for the clinic? AB - INTRODUCTION: Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation. Their etiology is multifactorial, with complex interactions between genetic and environmental factors, which are still largely unclear. AREAS COVERED: The influence of genetics is clearly demonstrated by important epidemiological data, including familial aggregation and concordance in twins. In 2001, the first genetic susceptibility gene for IBD, the NOD2 gene, was identified. Currently, thanks to genetic wide association studies, over 200 susceptibility genetic markers are know. Expert commentary: However, clinically highly relevant gene associations are still very limited and the usefulness of these information in the current clinical strategies for treatment and surveillance of IBD is weak. Nevertheless, the recent identification of some genetic risk variants has clarified some newbiological pathways of these diseases thus paving the way for the discoveries in the near future of new targeted therapies. PMID- 27258546 TI - Correction: Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli. AB - [This corrects the article DOI: 10.1371/journal.pone.0150182.]. PMID- 27258544 TI - Meta-Analysis of EMT Datasets Reveals Different Types of EMT. AB - As a critical process during embryonic development, cancer progression and cell fate conversions, epithelial-mesenchymal transition (EMT) has been extensively studied over the last several decades. To further understand the nature of EMT, we performed meta-analysis of multiple microarray datasets to identify the related generic signature. In this study, 24 human and 17 mouse microarray datasets were integrated to identify conserved gene expression changes in different types of EMT. Our integrative analysis revealed that there is low agreement among the list of the identified signature genes and three other lists in previous studies. Since removing the datasets with weakly-induced EMT from the analysis did not significantly improve the overlapping in the signature-gene lists, we hypothesized the existence of different types of EMT. This hypothesis was further supported by the grouping of 74 human EMT-induction samples into five distinct clusters, and the identification of distinct pathways in these different clusters of EMT samples. The five clusters of EMT-induction samples also improves the understanding of the characteristics of different EMT types. Therefore, we concluded the existence of different types of EMT was the possible reason for its complex role in multiple biological processes. PMID- 27258547 TI - Intratumoral Heterogeneity of MicroRNA Expression in Rectal Cancer. AB - INTRODUCTION: An increasing number of studies have investigated microRNAs (miRNAs) as potential markers of diagnosis, treatment and prognosis. So far, agreement between studies has been minimal, which may in part be explained by intratumoral heterogeneity of miRNA expression. The aim of the present study was to assess the heterogeneity of a panel of selected miRNAs in rectal cancer, using two different technical approaches. MATERIALS AND METHODS: The expression of the investigated miRNAs was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and in situ hybridization (ISH) in tumour specimens from 27 patients with T3-4 rectal cancer. From each tumour, tissue from three different luminal localisations was examined. Inter- and intra-patient variability was assessed by calculating intraclass correlation coefficients (ICCs). Correlations between RT-qPCR and ISH were evaluated using Spearman's correlation. RESULTS: ICCsingle (one sample from each patient) was higher than 50% for miRNA-21 and miRNA-31. For miRNA-125b, miRNA-145, and miRNA-630, ICCsingle was lower than 50%. The ICCmean (mean of three samples from each patient) was higher than 50% for miRNA-21(RT-qPCR and ISH), miRNA-125b (RT-qPCR and ISH), miRNA-145 (ISH), miRNA 630 (RT-qPCR), and miRNA-31 (RT-qPCR). For miRNA-145 (RT-qPCR) and miRNA-630 (ISH), ICCmean was lower than 50%. Spearman correlation coefficients, comparing results obtained by RT-qPCR and ISH, respectively, ranged from 0.084 to 0.325 for the mean value from each patient, and from -0.085 to 0.515 in the section including the deepest part of the tumour. CONCLUSION: Intratumoral heterogeneity may influence the measurement of miRNA expression and consequently the number of samples needed for representative estimates. Our findings with two different methods suggest that one sample is sufficient for adequate assessment of miRNA-21 and miRNA-31, whereas more samples would improve the assessment of miRNA-125b, miRNA-145, and miRNA-630. Interestingly, we found a poor correlation between the expression estimates obtained by RT-qPCR and ISH, respectively. PMID- 27258548 TI - Identification of the C-Terminal GH5 Domain from CbCel9B/Man5A as the First Glycoside Hydrolase with Thermal Activation Property from a Multimodular Bifunctional Enzyme. AB - Caldicellulosiruptor bescii encodes at least six unique multimodular glycoside hydrolases crucial for plant cell wall polysaccharides degradation, with each having two catalytic domains separated by two to three carbohydrate binding modules. Among the six enzymes, three have one N- or C-terminal GH5 domain with identical amino acid sequences. Despite a few reports on some of these multimodular enzymes, little is known about how the conserved GH5 domains behave, which are believed to be important due to the gene duplication. We thus cloned a representative GH5 domain from the C-terminus of a multimodular protein, i.e. the bifunctional cellulase/mannanase CbCel9B/Man5A which has been reported, and expressed it in Escherichia coli. Without any appending CBMs, the recombinant CbMan5A was still able to hydrolyze a variety of mannan substrates with different backbone linkages or side-chain decorations. While CbMan5A displayed the same pH optimum as CbCel9B/Man5A, it had an increased optimal temperature (90 degrees C) and moreover, was activated by heating at 70 degrees C and 80 degrees C, a property not ever reported for the full-length protein. The turnover numbers of CbMan5A on mannan substrates were, however, lower than those of CbCel9B/Man5A. These data suggested that evolution of CbMan5A and the other domains into a single polypeptide is not a simple assembly; rather, the behavior of one module may be affected by the other ones in the full-length enzyme. The differential scanning calorimetry analysis further indicated that heating CbMan5A was not a simple transition state process. To the best knowledge of the authors, CbMan5A is the first glycoside hydrolase with thermal activation property identified from a multimodular bifunctional enzyme. PMID- 27258549 TI - Light-Induced Charge Separation in Densely Packed Donor-Acceptor Coordination Cages. AB - Photon-powered charge separation is achieved in a supramolecular architecture based on the dense packing of functional building blocks. Therefore, self assembled dimers of interpenetrated coordination cages consisting of redoxactive chromophors were synthesized in a single assembly step starting from easily accessible ligands and Pd(II) cations. Two backbones consisting of electron rich phenothiazine (PTZ) and electron deficient anthraquinone (ANQ) were used to assemble either homo-octameric or mixed-ligand double cages. The electrochemical and spectroscopic properties of the pure cages, mixtures of donor and acceptor cages and the mixed-ligand cages were compared by steady-state UV-vis and transient absorption spectroscopy, supported by cyclic voltammetry and spectroelectrochemistry. Only the mixed-ligand cages, allowing close intra assembly communication between the donors and acceptors, showed the evolution of characteristic PTZ radical cation and ANQ radical anion features upon excitation in the transient spectra. In contrast, excitation of the mixtures of the homo octameric donor and acceptor cages in solution did not lead to any signs of electron transfer. Densely packed photo- and redox-functional self-assemblies promise molecular-level control over the morphology of the charge separation layer in future photovoltaic applications. PMID- 27258550 TI - Commensurate CO2 Capture, and Shape Selectivity for HCCH over H2CCH2, in Zigzag Channels of a Robust Cu(I)(CN)(L) Metal-Organic Framework. AB - A novel copper(I) metal-organic framework (MOF), {[Cu(I)2(py-pzpypz)2(MU CN)2].MeCN}n (1.MeCN), with an unusual topology is shown to be robust, retaining crystallinity during desolvation to give 1, which has also been structurally characterized [py-pzpypz is 4-(4-pyridyl)-2,5-dipyrazylpyridine)]. Zigzag-shaped channels, which in 1.MeCN were occupied by disordered MeCN molecules, run along the c axis of 1, resulting in a significant solvent-accessible void space (9.6% of the unit cell volume). These tight zigzags, bordered by (Cu(I)CN)n chains, make 1 an ideal candidate for investigations into shape-based selectivity. MOF 1 shows a moderate enthalpy of adsorption for binding CO2 (-32 kJ mol(-1) at moderate loadings), which results in a good selectivity for CO2 over N2 of 4.8:1 under real-world operating conditions of a 15:85 CO2/N2 mixture at 1 bar. Furthermore, 1 was investigated for shape-based selectivity of small hydrocarbons, revealing preferential uptake of linear acetylene gas over ethylene and methane, partially due to kinetic trapping of the guests with larger kinetic diameters. PMID- 27258551 TI - Correction: Microencapsulation of probiotics in hydrogel particles: enhancing Lactococcus lactis subsp. cremoris LM0230 viability using calcium alginate beads. AB - Correction for 'Microencapsulation of probiotics in hydrogel particles: enhancing Lactococcus lactis subsp. cremoris LM0230 viability using calcium alginate beads' by Timothy W. Yeung et al., Food Funct., 2016, 7, 1797-1804. PMID- 27258552 TI - Towards Sustainable Aquafeeds: Complete Substitution of Fish Oil with Marine Microalga Schizochytrium sp. Improves Growth and Fatty Acid Deposition in Juvenile Nile Tilapia (Oreochromis niloticus). AB - We conducted a 84-day nutritional feeding experiment with dried whole cells of DHA-rich marine microalga Schizochytrium sp. (Sc) to determine the optimum level of fish-oil substitution (partial or complete) for maximum growth of Nile tilapia. When we fully replaced fish oil with Schizochytrium (Sc100 diet), we found significantly higher weight gain and protein efficiency ratio (PER), and lower (improved) feed conversion ratio (FCR) and feed intake compared to a control diet containing fish oil (Sc0); and no significant change in SGR and survival rate among all diets. The Sc100 diet had the highest contents of 22:6n3 DHA, led to the highest DHA content in fillets, and consequently led to the highest DHA:EPA ratios in tilapia fillets. Schizochytrium sp. is a high quality candidate for complete substitution of fish oil in juvenile Nile tilapia feeds, providing an innovative means to formulate and optimize the composition of tilapia juvenile feed while simultaneously raising feed efficiency of tilapia aquaculture and to further develop environmentally and socially sustainable aquafeeds. Results show that replacing fish oil with DHA-rich marine Sc improves the deposition of n3 LC PUFA levels in tilapia fillet. These results support further studies to lower Schizochytrium production costs and to combine different marine microalgae to replace fish oil and fishmeal into aquafeeds. PMID- 27258553 TI - Genetic testing for the risk of developing late effects among survivors of childhood cancer: Consumer understanding, acceptance, and willingness to pay. AB - BACKGROUND: Genetic testing to determine cancer survivors' risk of developing late effects from their cancer treatment will be increasingly used in survivorship care. This 2-stage study with 64 survivors of childhood cancer and their parents investigated the preferences and acceptability of testing among those who may be at risk of developing late effects. METHODS: The first stage (Stage 1) identified the most commonly perceived benefits and concerns regarding genetic testing for the risk of late effects among 24 participants. In Stage 2, during interviews, 20 survivors (55% of whom were female; mean age, 26.0 years [range, 18-39 years]; standard deviation [SD], 0.80) and 20 parents (55% of whom were male; mean age of child survivor, 14.2 years [range, 10-19 years]; SD, 0.79) rated the 7 most common benefits and concerns from those identified in Stage 1. Interviews were transcribed verbatim and analyzed. Decisional balance ratios were calculated by dividing the participants' average concerns scores with the average benefits scores. RESULTS: Genetic testing for late effects was highly acceptable: 95% of participants leaned toward testing, and the majority (65.9%) would pay up to Australian $5000. The majority (97.2%) reported it was acceptable to wait for up to 6 months to receive results, and to be offered testing immediately after treatment or when the survivor reached adulthood (62.9%). Survivors and parents had a highly positive decisional balance (Mean (M), 0.5 [SD, 0.38] and M, 0.5 [SD, 0.39], respectively), indicating that perceived benefits outweighed concerns. CONCLUSIONS: Although to our knowledge clinical efficacy has yet to be clearly demonstrated, survivors and parents described positive interest in genetic testing for the risk of developing late effects. Perceived benefits outweighed harms, and the majority of participants would be willing to pay, and wait, for testing. Cancer 2016. (c) 2016 American Cancer Society. Cancer 2016;122:2876-2885. (c) 2016 American Cancer Society. PMID- 27258556 TI - Tandem Synthesis of 10-Dimethylaminobenzo[h]quinazolines from 2-Ketimino-1,8 bis(dimethylamino)naphthalenes via Nucleophilic Replacement of the Unactivated Aromatic NMe2 Group. AB - It has been found that 2-bromo-1,8-bis(dimethylamino)naphthalene on sequential treatment with n-BuLi and 2 equiv of the same or different aryl(hetaryl) cyanide as a result of [2 + 2 + 2] nucleophilic cascade annulation produces 10 dimethylaminobenzo[h]quinazolines, as yet unknown NMe2/-N? analogues of the proton sponge. It is even more convenient to use preliminarily prepared 2 ketimino-1,8-bis(dimethylamino)naphthalenes as starting material. The substitution of both peri-NMe2 groups furnishing quinazolino[7,8-h]quinazoline derivatives is also possible. The process is remarkable by surprisingly mild nucleophilic displacement of an unactivated aromatic NMe2 group. PMID- 27258555 TI - Application of a Combined Model with Autoregressive Integrated Moving Average (ARIMA) and Generalized Regression Neural Network (GRNN) in Forecasting Hepatitis Incidence in Heng County, China. AB - BACKGROUND: Hepatitis is a serious public health problem with increasing cases and property damage in Heng County. It is necessary to develop a model to predict the hepatitis epidemic that could be useful for preventing this disease. METHODS: The autoregressive integrated moving average (ARIMA) model and the generalized regression neural network (GRNN) model were used to fit the incidence data from the Heng County CDC (Center for Disease Control and Prevention) from January 2005 to December 2012. Then, the ARIMA-GRNN hybrid model was developed. The incidence data from January 2013 to December 2013 were used to validate the models. Several parameters, including mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) and mean square error (MSE), were used to compare the performance among the three models. RESULTS: The morbidity of hepatitis from Jan 2005 to Dec 2012 has seasonal variation and slightly rising trend. The ARIMA(0,1,2)(1,1,1)12 model was the most appropriate one with the residual test showing a white noise sequence. The smoothing factor of the basic GRNN model and the combined model was 1.8 and 0.07, respectively. The four parameters of the hybrid model were lower than those of the two single models in the validation. The parameters values of the GRNN model were the lowest in the fitting of the three models. CONCLUSIONS: The hybrid ARIMA-GRNN model showed better hepatitis incidence forecasting in Heng County than the single ARIMA model and the basic GRNN model. It is a potential decision-supportive tool for controlling hepatitis in Heng County. PMID- 27258557 TI - Host-Guest Assembly of a Molecular Reporter with Chiral Cyanohydrins for Assignment of Absolute Stereochemistry. AB - The absolute stereochemistry of cyanohydrins, derived from ketones and aldehydes, is obtained routinely, in a microscale and derivatization-free manner, upon their complexation with Zn-MAPOL, a zincated porphyrin host with a binding pocket comprised of a biphenol core. The host-guest complex leads to observable exciton coupled circular dichroism (ECCD), the sign of which is easily correlated to the absolute stereochemistry of the bound cyanohydrin. A working model, based on the ECCD signal of cyanohydrins with known configuration, is proposed. PMID- 27258558 TI - Fluorescent Immunohistochemistry: An Important Tool to Reveal Proteins From Tissues in Ancient Mummified Remains. AB - During the restoration of the Saint Antonio Abate Cathedral in Castelsardo, Sardinia, Italy, numerous human remains were found in a crypt. The burial site contained upwards of 120 individuals organized in successive layers from the bottom of the crypt; of these, 18 partially mummified individuals have been identified, including the last 2 individuals buried in the crypt. In the present study, we focused on these 2 individuals by initially adopting a morphologic and anthropological approach. The anthropological analysis of the remains showed that the 2 bodies were partially mummified and that most of the organs were not available; for this reason, the sex was determined by secondary sexual characteristics of the skulls and the long bones. The aim of this research was to describe the general state of the mummified bodies and tissues by morphologic and ultrastructural analysis using light and electron microscopy techniques. To ensure the preservation of specific tissue proteins, immunohistochemical fluorescence analysis was used. Limited information is available regarding the preservation of mummified tissues. Thus, this study demonstrated the presence of muscle and skin tissue markers in a good state of preservation, even though the tissues had undergone a slow mummification process. Our results demonstrate that several types of tissues and cell proteins may survive over a prolonged period and that these materials survive the postmortem processes. PMID- 27258559 TI - Nucleolar Cytokeratin 19 in Thyroid Carcinoma. PMID- 27258561 TI - Small Bowel Adenocarcinoma Frequently Exhibits Lynch Syndrome-associated Mismatch Repair Protein Deficiency But Does Not Harbor Sporadic MLH1 Deficiency. AB - Universal screening for Lynch syndrome has been advocated for colorectal carcinoma but its utility in small bowel adenocarcinoma has not been reported. We analyzed a consecutive series of 71 small bowel adenocarcinomas identified over an 8-year period for DNA mismatch repair (MMR) protein expression to (1) compare the clinicopathologic features of small bowel adenocarcinoma stratified into MMR deficient (MMRD) and MMR-proficient (MMRP) groups and (2) examine the patterns of MMR protein expression in small bowel adenocarcinoma compared with colorectal carcinoma. Six of 71 (8.5%) small bowel adenocarcinomas and 149 of 1291 (11.5%) colorectal carcinomas demonstrated MMRD. The 6 MMRD small bowel adenocarcinomas had the following expression pattern: 3 with concurrent loss of MSH2 and MSH6, 1 with isolated loss of MSH6, and 2 with concurrent loss of MLH1 and PMS2 in patients with a family history suggestive of genetic cancer susceptibility. Histopathology suggestive of MMR protein deficiency as proposed by the revised Bethesda guidelines was commonly seen in both MMRP (63%) and MMRD (67%) small bowel adenocarcinomas (P>0.05). MMRD small bowel adenocarcinoma more frequently demonstrated abnormalities of MSH2 and/or MSH6 (4/6, 67%) compared with MMRD colorectal carcinoma (23/149, 15%) (P=0.01). None of the MMRD small bowel adenocarcinomas harbored the BRAF V600E mutation, whereas 60% of MMRD colorectal carcinomas were positive for BRAF V600E with concurrent loss of MLH1 and PMS2 expression. Small bowel adenocarcinoma more frequently harbored Lynch syndrome associated MMRD compared with colorectal carcinoma, providing support for screening of small bowel adenocarcinoma to identify patients at risk for Lynch syndrome. In contrast to colorectal carcinoma, sporadic MLH1 deficiency is not seen in small bowel adenocarcinoma. Clinicopathologic and histologic features do not distinguish between MMRP and MMRD small bowel adenocarcinoma indicating that universal screening in small bowel adenocarcinoma is necessary to detect patients at risk for Lynch syndrome. PMID- 27258560 TI - The Role of SATB2 as a Diagnostic Marker of Sinonasal Intestinal-type Adenocarcinoma. AB - BACKGROUND: Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses is an uncommon tumor associated with exposure to wood and leather dust, nickel, and possibly smoking. ITAC shares phenotypical features with colorectal carcinoma. In contrast to most non-intestinal-type sinonasal adenocarcinomas, ITAC is an aggressive adenocarcinoma with poor clinical outcome; therefore, its reliable separation from non-ITAC is very important. AIM: The use of a combination of immunohistochemical markers of intestinal differentiation was tested in a cohort of sinonasal carcinomas of different types. The aim of this study was to explore a new intestinal marker, SATB2, in conjunction with CDX2 and CK20 in differential diagnosis of sinonasal adenocarcinomas. MATERIALS AND METHODS: Seven ITACs, 66 non-ITACs, and 1 case of extensive intestinal metaplasia (IM) of the nasal mucosa were included in the study and stained with SATB2, CK20, CDX2, and CK7 antibodies. Detection of mismatch repair proteins was performed in all cases of ITAC. All 7 sinonasal ITACs have been tested for KRAS, NRAS, and BRAF gene mutations. RESULTS: All ITACs showed positive expression for SATB2, whereas all non-ITAC cases were negative. The only 1 case of IM was found to be positive for SATB2, whereas the same case showed negative expression of CK20 and only focal immunostaining for CDX2. The genetic analysis showed that only 1 sinonasal ITAC (1/7) showed KRAS c.35G>C, p.(Gly12Ala) mutation, whereas BRAF and NRAS genes were wild type. Four ITACs revealed wild-type KRAS, NRAS, and BRAF, and 2 remaining cases were not analyzable. All ITACs showed preserved nuclear expression of mismatch repair proteins. CONCLUSIONS: SATB2 in combination with CDX2 and CK20 differentiates sinonasal ITAC from non-ITAC with increased diagnostic sensitivity and specificity and detects IM in the sinonasal tract more easily. PMID- 27258562 TI - pSTAT3/pSTAT5 Signaling Patterns in Molecularly Defined Subsets of Myeloproliferative Neoplasms. AB - BCR/ABL1-negative myeloproliferative neoplasms (MPNs) are characterized by recurrent mutations in JAK2, CALR, and MPL, each of which has been reported to alter JAK/STAT signaling pathways. This report characterizes JAK/STAT signaling patterns in molecularly defined subsets of MPN utilizing immunohistochemistry for pSTAT3 and pSTAT5. Analysis of 30 BCR/ABL1-negative, nonpolycythemia vera MPN identified 15 (50%) with JAK2 V617F, 2 with MPL mutations (7%), and 8 with CALR mutations (27%). All mutations were mutually exclusive, except for 1 case with concurrent JAK2 V617F and CALR mutations. pSTAT3 staining in megakaryocyte nuclei was found in 4 cases (13%) and was not significantly associated with mutation status. pSTAT5 staining in megakaryocyte nuclei was found in 16 cases (53%), as was significantly associated with JAK2 V617F versus CALR mutation (P=0.009). Erythroid staining for pSTAT5 was seen exclusively in "triple-negative (TN)" cases lacking JAK2 V617F, MPL, and CALR mutations (P=0.006, TN vs. other genotypes), and pSTAT5 staining in megakaryocyte nuclei was seen in 2 TN cases. pSTAT5 staining in TN MPN suggests that other unknown abnormalities in this pathway may contribute to the pathogenesis of these cases. Furthermore, the demonstration of distinct STAT staining patterns in molecularly defined MPN suggests that these mutations result in divergent signaling events that may contribute to the biological and prognostic differences in these molecular subsets of MPN. PMID- 27258563 TI - Overexpression of TACC3 in Breast Cancer Associates With Poor Prognosis. AB - Increasing evidences suggest that transforming acidic coiled-coil protein 3 (TACC3) is associated with various types of human cancer. However, the expression of TACC3 in breast cancer tissues remains largely unknown. To identify whether TACC3 can serve as a biomarker for the diagnosis and prognosis of breast cancer, quantitative polymerase chain reaction, western blotting, and immunohistochemistry staining were utilized to detect the expression of TACC3. The mRNA and protein levels of TACC3 in breast cancer samples were novelty higher compared with nontumorous breast tissues. Immunohistochemistry results revealed TACC3 expression was significantly correlated to lymphoid nodal metastasis (P=0.035) and HER-2 status (P=0.021). The patients with high expression of TACC3 had a significantly poor prognosis compared with patients with low expression (P=0.017), especially in the patients with pathological tumor size 2-4 status (P=0.028). Furthermore, multivariate analysis indicated that TACC3 expression was an independent prognostic factor for breast cancer patients (P=0.029). This study, first, suggested TACC3 might be an important molecular marker for diagnosis and prognosis of breast cancer. PMID- 27258564 TI - Identification of New Biomarkers Associated With IDH Mutation and Prognosis in Astrocytic Tumors Using NanoString nCounter Analysis System. AB - BACKGROUND: Isocitrate dehydrogenase (IDH) mutations have been reported as biomarkers associated with tumorigenesis and prognosis in gliomas. However, genes affected by these mutations are still under investigation. The purpose of this study is to identify new molecular biomarkers associated with IDH mutation and prognosis in astrocytic tumors, which account for the largest proportion of gliomas. MATERIALS AND METHODS: NanoString analysis was conducted on 40 astrocytic tumors. In total, 69 genes and 6 fusion genes were selected for screening. Quantitative real-time polymerase chain reaction and immunohistochemistry were used to validate the selected discriminatory genes. Kaplan-Meier survival curves and log-rank test were used to analyze the overall survival and progression-free survival. RESULTS: mRNA levels of NTRK3, ERCC1, JAK2, AXL, BCL2, ESR1, HSP90AB1, TUBB3, RET, and ABCG2 were elevated in the IDH mutant group, whereas levels of POSTN and ERBB2 were elevated in the IDH wild type group. Genes more highly expressed in the better prognosis group included NTRK3, ERCC1, ROS1, ERBB4, BCL2, CDKN2A, AXL, PI3KCA, HSP90AB1, ABCG2, JAK2, and RET. In the worse prognosis group, TIMP1, POSTN, and ERBB2 showed increased expressions. The elevated expression of HSP90AB1 was correlated with IDH mutation, long survival, and secondary glioblastomas. Elevated TIMP1 expression was related to high tumor grade and short patient survival. The results of NanoString were confirmed with quantitative real-time polymerase chain reaction and immunohistochemistry. CONCLUSIONS: HSP90AB1 is related to IDH mutation and the expressions of HSP90AB1 and TIMP1 can predict prognosis in astrocytic tumors. The NanoString analysis system is a precise and reliable method to detect mRNA expression in formalin-fixed paraffin-embedded samples. PMID- 27258565 TI - MCM3: A Novel Proliferation Marker in Oral Squamous Cell Carcinoma. AB - The present study sought to evaluate and compare the immunoexpression of proteins minichromosome maintenance (MCM) 3 and Ki-67 in oral squamous cell carcinoma (OSCC) to assess the potential of these proteins as markers of cellular proliferation. Twenty-eight cases of OSCC, 9 of tumor-free resection margins (TM), and 4 of non-neoplastic oral mucosa (NNM) were subjected to immunohistochemistry to detect the expression of proteins MCM3 and Ki-67. All OSCCs demonstrated positivity for both proteins. In these tumors, greater MCM3 immunoreactivity was observed in comparison with Ki-67, whereas TMs and NNMs exhibited greater Ki-67 expression compared with MCM3. The immunoexpression of Ki 67 seemed to be influenced by the inflammatory process, particularly in TM and NNM. Our findings indicate that although both MCM3 and Ki-67 represent reliable markers of cellular proliferation in OSCC, as MCM3 expression does not appear to be influenced by external factors, this protein may emerge as a novel marker of cellular proliferation in these types of tumors. PMID- 27258566 TI - Gastrointestinal Stromal Tumor: Genotype Frequency and Prognostic Relevance. AB - BACKGROUND: Genotyping has an important role in the prognosis and prediction of response to tyrosine kinase inhibitor therapy. KIT exon 11 deletions serve as an adverse prognostic marker. Gastrointestinal stromal tumor (GIST) genotype has been described in developed countries; however, data from India are lacking. The aim of this study was to determine the genotype frequency and its prognostic relevance. MATERIALS AND METHODS: Eighty consecutive cases of resected GIST were evaluated for histologic and immunohistochemical findings. Mutation analysis for exons 9, 11, 13, and 17 of KIT and 12 and 18 of PDGFRA was carried out by PCR Sanger sequencing. Genotypes were correlated with risk groups, recurrence, and imatinib therapy. RESULTS: Forty-seven of 80 cases (58.7%) showed mutations, including 30 cases (37.5%) in KIT exon 11, 9 cases (11.2%) in KIT exon 9, and 8 cases (10%) in PDGFRA exon 18. Codon 557-558 deletion was present in 15 cases. D842E was the most common in PDGFRA, with similar histologic features as D842V. KIT exon 11 deletion had higher mitotic rate, larger tumor size, high-risk stratification, and lower recurrence-free survival. Recurrences were seen in 12 (16.4%) patients. Nine patients (75%) with recurrence were on imatinib therapy. CONCLUSIONS: GIST genotype frequency is lower in Indians. KIT exon 11 deletion is associated with poor prognosis compared with wild-type and other missense mutations. D842E is a common PDGFRA mutation in Indian patients. Patients with a wild genotype are not suitable candidates for imatinib therapy. Genotyping can serve as an important prognostic marker. PMID- 27258567 TI - The Use of a Novel Immunohistochemical Triple Cocktail in the Subclassification of Resected Non-Small Cell Lung Carcinomas: A Comparative Study With Morphology and Traditional Immunohistochemistry. AB - Therapy for non-small cell lung carcinoma (NSCLC) is currently determined by histologic subtype and the presence or absence of actionable mutations. Accurate subclassification is therefore essential for appropriate selection of cases for molecular studies and guiding treatment. The gold standard for subclassification of NSCLC is identification of differentiating morphologic features in correlation with diagnostic immunohistochemistry (IHC) in cases of poorly differentiated carcinoma. Whereas Napsin A, TTF1, and p40 antibodies have been used individually for the subtyping of NSCLC, few studies have examined the 3 in cocktail form. Using a novel triple IHC antibody cocktail (TNP) composed of TTF1 (brown nuclear), Napsin A (red granular cytoplasmic), and p40 (red nuclear), a randomized, double-blinded subclassification was performed on a representative histologic section of 32 previously resected primary NSCLCs. TNP results were then compared with the gold-standard diagnosis. TNP accurately identified all (100%, 10/10) squamous cell carcinomas (SCCs) (p40+/TTF1-/Napsin A-) and 89% (16/18) of adenocarcinomas (ADCs) (p40-/TTF1+/Napsin A+). TNP was negative in 7 (20%) tumors (p40-/TTF1-/Napsin A-), including 2 mucinous ADCs. TNP showed no overlapping or discordant immunostaining. Using traditional IHC with p63, CK5/6, and TTF1, all TNP (-) cases remained unclassifiable. With the exception of mucinous ADC, which was TNP negative, all TNP cases correlated with gold-standard diagnosis; 78% of tumors were also definitively classified as either ADC or SCC and required only a single slide for classification. PMID- 27258568 TI - Artificial Force Induced Reaction (AFIR) Method for Exploring Quantum Chemical Potential Energy Surfaces. AB - In this account, a technical overview of the artificial force induced reaction (AFIR) method is presented. The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chemical reactions, such as organocatalysis, organometallic catalysis, and photoreactions. There are two modes in the AFIR method, i.e., a multicomponent mode and a single-component mode. The former has been applied to bimolecular and multicomponent reactions and the latter to unimolecular isomerization and dissociation reactions. Five numerical examples are presented for an Aldol reaction, a Claisen rearrangement, a Co-catalyzed hydroformylation, a fullerene structure search, and a nonradiative decay path search in an electronically excited naphthalene molecule. Finally, possible applications of the AFIR method are discussed. PMID- 27258569 TI - Anti-Ambipolar Field-Effect Transistors Based On Few-Layer 2D Transition Metal Dichalcogenides. AB - Two-dimensional (2D) materials and their related van der Waals heterostructures have attracted considerable interest for their fascinating new properties. There are still many challenges in realizing the potential of 2D semiconductors in practical (opto)electronics such as signal transmission and logic circuit, etc. Herein, we report the gate-tunable anti-ambipolar devices on the basis of few layer transition metal dichalcogenides (TMDs) heterostructures to gain higher information storage density. Our study shows that carrier concentration regulated by the gate voltage plays a major role in the "anti-ambipolar" behavior, where the drain-source current can only pass through in specific range of gate voltage (Vg) and it will be restrained if the Vg goes beyond the range. Several improved strategies were theoretically discussed and experimentally adopted to obtain higher current on/off ratio for the anti-ambipolar devices, such as choosing suitable p-/n-pair, increasing carrier concentration by using thicker-layer TMDs, and so on. The modified SnS2/WSe2 device with the current on/off ratio exceeding 200 and on-state Vg ranging from -20 to 0 V was successfully achieved. On the basis of the anti-ambipolar field-effect transistors (FETs), we also reveal the potential of three-channel device unit for signal processing and information storage. With the equal quantity N of device units, 3(N) digital signals can be obtained from such three-channel devices, which are much larger than 2(N) ones obtained from traditional two-channel complementary metal oxide semiconductors (CMOS). PMID- 27258570 TI - Changes in Exercise Patterns in Menopausal Women at Low-Intermediate Risk for Cardiovascular Disease: A Prospective Survey Study. AB - INTRODUCTION: We aim to describe changes in exercise habits and barriers to physical activity over 5 years in menopausal women at low-intermediate risk for cardiovascular disease. MATERIALS AND METHODS: Women in the Stress Echocardiography in Menopausal Women at Risk for Coronary Artery Disease trial were prospectively enrolled in a multisite study from 2004 to 2007. Inclusion criteria were as follows: peri- and postmenopausal women with symptoms and/or risk factors for cardiovascular disease resulting in referral for stress echocardiography. A questionnaire, which assessed details of medical history, physical activity, and body mass index (BMI), was administered at baseline and 5 years. RESULTS: 216 menopausal women (62.5% hypertensive, 15.3% diabetic, 52.3% prior or current smokers) were studied. At baseline, age was 54.9 +/- 4.8 years, BMI was 30.7 +/- 6.4 kg/m2, and Framingham risk score was 4.05% +/- 3.76%. One hundred women (46.3%) were obese, 79 (36.6%) overweight, and 37 (17.1%) had a normal BMI. Women changed their self-reported aerobic exercise patterns in similar patterns regardless of their BMI at baseline. There was low participation in strength training among all women. Mean BMI decreased by 0.12 kg/m2 in obese women and increased by 1.63 kg/m2 in normal BMI women at 5 years (p < 0.0001). CONCLUSION: These data suggest that women can increase their level of physical activity regardless of BMI and that overweight or obese status is not a barrier to initiating an aerobic, nonaerobic, or strength training exercise routine. PMID- 27258571 TI - The role of photorespiration during astaxanthin accumulation in Haematococcus pluvialis (Chlorophyceae). AB - Most previous studies on Haematococcus pluvialis have been focused on growth and astaxanthin accumulation. However, the relationships between photorespiration and astaxanthin accumulation have not been clarified. The purpose of this study was to examine the role of photorespiration during the process of astaxanthin accumulation in H. pluvialis. During astaxanthin accumulation, the astaxanthin content was reduced significantly when photorespiration was inhibited by its specific inhibitor, carboxymethoxylamine. The inhibition of photorespiration did not change the dry weight, chlorophyll content and OJIP transients during the incubation; however, the inhibition of photorespiration significantly decreased the photochemistry of photosystem II and total photosynthetic O2 evolution capacity. Moreover, the restriction in photorespiration was synchronized with a decrease of astaxanthin accumulation. These results suggest that the photorespiratory pathway in H. pluvialis can accelerate astaxanthin accumulation. We speculate that photorespiration can enhance astaxanthin accumulation in the following ways: (i) photorespiration directly affects the glycerate-3-phosphate (PGA) level, which is intrinsically related to the accumulation of astaxanthin in H. pluvialis; (ii) the photorespiratory pathway indirectly affects the PGA level by effecting the dark reactions of photosynthesis, which then results in the enhancement of astaxanthin accumulation in H. pluvialis. PMID- 27258572 TI - Combined herbicide and saline stress differentially modulates hormonal regulation and antioxidant defense system in Oryza sativa cultivars. AB - Plants are simultaneously exposed to a combination of biotic and abiotic stresses in field conditions. Crops respond to the combined stress in a unique way which cannot be understood by extrapolating the results of individual stress. In the present study, effects of individual and combined stress of herbicide (2,4 dichlorophenoxyacetic acid) and salinity (NaCl) on two Oryza sativa cultivars (ZJ 88 and XS 134) were investigated. Both herbicide and saline stress affected the plant growth differentially and produced oxidative stress in rice cultivars. Interestingly, the combination of herbicide and salinity showed a significant protection to both rice cultivars by reducing ROS (H2O2, O2(-)) and lipid peroxidation through modulation of enzymatic (SOD, POD, CAT and APX) and non enzymatic (TSP, sugars, phenolic and proline) antioxidants. In addition, active regulation of transcript levels of genes encoding Na(+) and K(+) (OsHKT1;5, OsLti6a,b, OsHKT2;1, OsSOS1, OsCNGC1, OsNHX1 and OsAKT1) transporter proteins reduced sodium and enhanced potassium accumulation under combined stress, resulted a better growth and ionic homeostasis in both rice cultivars. The production of ABA and IAA was significantly higher in cultivar XS 134 compared to cultivar ZJ 88 under control conditions. However, combined herbicide and saline stress enhanced the accumulation of phytohormones (IAA and ABA) and transcription of ethylene in cultivar ZJ 88, which might be one of the factors responsible for poor salt tolerance in sensitive cultivar. These findings indicated that herbicide application under saline stress confers tolerance to salinity in rice cultivars, likely by reducing oxidative damage, modulating mineral absorption, upgradation of antioxidant defense and by dynamic regulation of key genes involved in Na(+) and K(+) homeostasis in plants. PMID- 27258573 TI - A review on biomass production from C4 grasses: yield and quality for end-use. AB - With a dry biomass production exceeding 40Mgha(-1) in many environments, Miscanthus spp. is the most productive perennial C4 grass species thanks to five advantages over North American prairie tallgrasses. However, miscanthus has a slower nutrient remobilization system, resulting in higher nutrient concentrations at harvest. Perennial C4 grasses benefit from soil microbial associations, reducing their nutrient needs. For combustion purposes, grasses with low moisture content, high lignin and low nutrients are desired. For ethanol, preferred feedstock will have lower lignin, higher sugars, starch, or cellulose/hemicellulose depending on the conversion method. Species with high stem-to-leaf ratio provide better biofuel conversion efficiency and quality. Recently-developed transgenic switchgrass lines have much higher ethanol yields and lower transformation costs. Further selection and breeding are needed to optimize biomass quality and nutrient cycling. PMID- 27258574 TI - Comparison between pulsatile GnRH therapy and gonadotropins for ovulation induction in women with both functional hypothalamic amenorrhea and polycystic ovarian morphology. AB - CONTEXT: Ovulation induction in patients having both functional hypothalamic amenorrhea (FHA) and polycystic ovarian morphology (PCOM) has been less studied in the literature. As results remain contradictory, no recommendations have yet been established. OBJECTIVE: To compare pulsatile GnRH therapy versus gonadotropins for ovulation induction in "FHA-PCOM" patients and to determine if one treatment strikes as superior to the other. METHODS: A 12-year retrospective study, comparing 55 "FHA-PCOM" patients, treated either with GnRH therapy (38 patients, 93 cycles) or with gonadotropins (17 patients, 53 cycles). RESULTS: Both groups were similar, defined by low serum LH and E2 levels, low BMI, excessive follicle number per ovary and/or high serum AMH level. Ovulation rates were significantly lower with gonadotropins (56.6% versus 78.6%, p = 0.005), with more cancellation and ovarian hyper-responses (14% versus 34% per initiated cycle, p < 0.005). Pregnancy rates were significantly higher with GnRH therapy, whether per initiated cycle (26.9% versus 7.6%, p = 0.005) or per patient (65.8% versus 23.5%, p = 0.007). CONCLUSION: In our study, GnRH therapy was more successful and safer than gonadotropins, for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, it could become a first-line treatment for this population, just as it is for FHA women without PCOM. PMID- 27258576 TI - The future of pancreas transplantation: 'ain't what it used to be'. PMID- 27258575 TI - Non-HLA antibodies in transplantation: when do they matter? AB - PURPOSE OF REVIEW: A growing interest in the contribution of non-human leukocyte antigens (non-HLA) antibodies to allograft rejection has led to the identification of multiple target antigens and investigation into the possible mechanisms of injury. Although several non-HLA antibody specificities have been identified, the largest cohorts studied are those detected using commercial assays. This review focuses on the phenotypes of injury associated with non-HLA antibody and defines in-vivo environmental characteristics that may be conducive to non-HLA antibody-mediated injury. RECENT FINDINGS: Mechanistic studies in animal models and clinical data suggest that an inflammatory environment, increased antigen expression, and development of neoantigens through posttranslational modifications contribute to non-HLA antibody development and their subsequent contribution to allograft injury. Furthermore, many reports show worse outcomes when HLA and non-HLA antibodies are present, suggesting possible interactions between these antibodies that lead to increased injury. Plasmapheresis and intravenous immunoglobulin are currently used to reduce HLA and non-HLA antibodies; however, therapeutic strategies targeting B cells and plasma cells simultaneously may lead to more durable antibody elimination. SUMMARY: Immune triggers that lead to non-HLA antibody formation are complex and poorly understood. The ability of non-HLA antibodies to mediate allograft injury may depend upon their specificity and affinity, density of the target antigen, and synergy with HLA antibodies. PMID- 27258577 TI - Risk factors associated with the development of histocompatibility leukocyte antigen sensitization. AB - PURPOSE OF REVIEW: Despite excellent short-term kidney allograft survival rates, long-term outcomes have not improved. For years, the focus on improving these outcomes revolved around minimization or elimination of calcineurin toxicity. Despite our best efforts, approximately 5000 allografts are lost each year in the United States and results in a significant emotional burden for patients and financial burden for the healthcare system. RECENT FINDINGS: Advancements in detection of donor-specific histocompatibility leukocyte antigen antibodies (DSAs) and improved assessment of allograft biopsy tissue have shown that the most common cause for graft failures is DSA-related antibody-mediated rejection. Sensitization is directly related to human tissue exposure prior to transplant. We now know that sensitization can occur in patients who are non compliant or poorly compliant with their calcineurin inhibitors. They develop de-novo DSAs, which are responsible for numerous allograft losses around the world. SUMMARY: Given the current evidence, it is imperative that all transplant physicians recognize the importance of encouraging medication adherence to prevent the consequences of DSA-induced graft failure. However, little progress has been made in this area. Other potential therapeutic approaches based on B-cell depletion or modulation early posttransplant may help to reduce the risk for de-novo DSA development. PMID- 27258578 TI - Current outcomes in islet versus solid organ pancreas transplant for beta-cell replacement in type 1 diabetes. AB - PURPOSE OF REVIEW: With continued optimization of islet isolation and immunosuppression protocols, the medium-term rates of insulin independence following islet transplantation have improved significantly. This review evaluates the most up-to-date outcomes data for both solid organ pancreas and islet transplantation to develop an algorithm for selection of beta-cell replacement in type 1 diabetes patients. RECENT FINDINGS: Solid organ pancreas and islet transplantation have both displayed improved rates of 5-year insulin independence, largely attributable to improvements in immunosuppressive regimens. The medium-term rates of insulin independence following islet transplantation in highly selected type 1 nonuremic diabetic recipients is beginning to approach the success rates observed following solitary pancreas transplantation. SUMMARY: Although pancreas transplantation has historically been favored for beta-cell replacement, current outcomes following islet transplantation justify the use of this minimally invasive therapy in carefully selected patients. Pancreas transplant remains the procedure of choice for beta-cell replacement in uremic patients. Islet transplantation should be considered in nonuremic patients with low BMI and low insulin requirements, patients lacking the cardiovascular reserve to undergo open abdominal surgery, or patients who elect to forego the risks of a major operation in exchange for an increased risk of islet graft failure. PMID- 27258579 TI - Alloimmune-induced intragraft lymphoid neogenesis promotes B-cell tolerance breakdown that accelerates chronic rejection. AB - PURPOSE OF REVIEW: Antibody-mediated rejection (AMR) has emerged as a leading cause of allograft loss in solid organ transplantation. A better understanding of AMR immunopathology is a prerequisite to improve its management. RECENT FINDINGS: The prevalent dogma considers that AMR is the consequence of a thymo-dependent B cell response against donor-specific polymorphic antigens (mainly mismatched human leukocyte antigen molecules).Nevertheless, antibodies directed against nonpolymorphic antigens expressed by the graft are also generated during chronic rejection and can contribute to allograft destruction. This implies that a breakdown of self-tolerance occurs during chronic rejection. Accumulating evidence suggests that this event occurs inside the ectopic 'tertiary' lymphoid tissue that develops within rejected allografts.Thus, AMR should be viewed as a complex interplay between allo- and autoimmune humoral responses. SUMMARY: The interplay between allo- and autoimmune humoral responses in chronic rejection highlights several unmet medical issues like better diagnosis tools are needed to screen recipients for nonhuman leukocyte antigen alloantibodies and autoantibodies, therapeutic strategies shall aim at blocking the response against alloantigens but also the breakdown of self-tolerance that occurs within tertiary lymphoid tissue. PMID- 27258580 TI - Long-term outcome after pancreas transplantation: a registry analysis. AB - PURPOSE OF REVIEW: Pancreas transplantation provides the only proven method to restore long-term normoglycemia in patients with insulin-dependent diabetes mellitus. Although many studies describe the most important risk factors for short-term survival of a pancreas transplant, more information about factors that distinguish short-term from long-term graft function is needed. RECENT FINDINGS: Analysis of 21 328 pancreas transplants from the International Pancreas Transplant Registry, performed from 1984 to 2009 (minimum 5-year follow-up), shows a significant improvement in long-term patient survival and pancreas graft function. Total 5-and 10-year pancreas graft function rates are 73 and 56%, respectively, for simultaneous pancreas-kidney transplants; 64 and 38%, respectively, for pancreas after kidney; and 53 and 36%, respectively, for pancreas transplants alone. The most influential period is the first year posttransplant. Recipients who reach this time point with a functioning graft have a much higher probability for excellent long-term graft function. Important factors influencing long-term function were features that described the quality of the deceased donor. Pancreas transplants in younger, high panel reactive antibody, or African-American recipients also showed an increased risk of early graft failure. Anti-T-cell induction therapy had a significant impact on long term survival in solitary transplants. SUMMARY: With careful recipient and donor selection and close follow-up in the first year posttransplant, not only good short-term but also long-term pancreas graft function and, therefore, durable metabolic control can be achieved for the diabetic patient. PMID- 27258581 TI - WITHDRAWN: Chuanxiong preparations for preventing stroke. PMID- 27258582 TI - Enantioselective Recognition by Chiral Supramolecular Gels. AB - Chiral supramolecular gels, in which small organic molecules self-assemble into chiral nanostructures and entangle each other to immobilize solvents through various noncovalent interactions, can work as a matrix for enantioselective recognition on chiral analytes. Through gelation and the formation of well defined nanostructures, the chiral sense of the component molecules can be accumulated or amplified, and thus, the enantioselective recognition ability can be enhanced. Furthermore, a chiral microenvironment formed in the gel networks could provide additional stereochemical recognition geometry and attribute to efficient recognition. In this focus review, enantioselective recognition on chiral analytes through chiral supramolecular gels, with either amplified signals or the gel-sol phase transition, is discussed. This review is expected to provide useful insights into the design and fabrication of supramolecular gel systems with chiral features and high enantioselectivity. PMID- 27258583 TI - "It is always HIV/AIDS and TB": Home-based carers' perspectives on epilepsy in Cape Town, South Africa. AB - The study highlights the complex cultural religious factors affecting epilepsy and a need for integrated home-based care services. Two focus group discussions exploring home-based carers' (HBCs) perspectives on epilepsy were conducted using a semi-structured focus group interview guide, which was based on Kleinman's explanatory model framework. The audio-recorded data were transcribed verbatim, and a thematic analysis was done. The three main themes were epilepsy names and metaphors, religious beliefs about the cause and treatment of epilepsy, and HBCs' perceived roles and strategies for engaging in epilepsy care. Findings provide some insights for research, policy, and practice. PMID- 27258584 TI - Hospice nurses' emotional challenges in their encounters with the dying. AB - The purpose of this study was to explore nurses' emotional challenges when caring for the dying in hospices. The study has a qualitative design, and knowledge was developed through a dialectical exchange between theory and data. Ten individual in-depth interviews were conducted with nurses recruited from two hospices in Denmark. Although all of the nurses said that they experienced emotional challenges or felt emotionally touched during their work, the study found a variety of opinions related to the extent to which their emotional reactions should be revealed in their role as a hospice professional. The participants described their emotional challenges as being simultaneously draining and enriching experiences leading to personal and professional growth and development. The study may contribute to increased awareness of emotional challenges for hospice nurses, which involve continuous reflection and balancing between meeting the dying as a human being and meeting the dying as a hospice professional. PMID- 27258585 TI - Suicidality in Huntington's Disease: A Qualitative Study on Coping Styles and Support Strategies. AB - BACKGROUND: Huntington's disease (HD) mutation carriers are at increased risk of suicidal ideation, suicide attempts, and completed suicide. However, research is lacking on coping strategies and treatment options that can be offered to suicidal HD mutation carriers. OBJECTIVE: This study explores how individuals with pre-motor or motor symptomatic HD cope with suicidality, how their partners support them, and their ideas and wishes regarding how relatives and healthcare professionals can help them in coping with suicidality. METHODS: This qualitative study included 11 HD mutation carriers who experienced suicidal ideation or attempted suicide and 3 of their partners. They participated in a focus group discussion or an individual in-depth interview. Two independent researchers fragmented the transcribed interviews, coded these fragments, grouped them under themes, and structured the data. RESULTS: HD study participants used four main strategies to cope with suicidality, including talking about suicidality, employing self-management activities, using medication, and discussing end-of life wishes. Partners, relatives, and healthcare professionals can support suicidal HD mutation carriers in each of those four strategies. CONCLUSIONS: Despite the absence of a turnkey solution for suicidality in HD, healthcare professionals can play an important role in supporting suicidal HD mutation carriers by providing an opportunity to talk about suicidality, providing psychoeducation on self-management, prescribing medication, and discussing end-of life wishes. Future HD-specific intervention studies could investigate the effect of combining these treatment strategies into one holistic approach. PMID- 27258587 TI - Notice of Retraction: Sato Y, et al. Risedronate Sodium Therapy for Prevention of Hip Fracture in Men 65 Years or Older After Stroke. Arch Intern Med. 2005;165(15):1743-1748. PMID- 27258586 TI - A Longitudinal Motor Characterisation of the HdhQ111 Mouse Model of Huntington's Disease. AB - BACKGROUND: Huntington's disease (HD) is a rare, incurable neurodegenerative disorder caused by a CAG trinucleotide expansion with the first exon of the huntingtin gene. Numerous knock-in mouse models are currently available for modelling HD. However, before their use in scientific research, these models must be characterised to determine their face and predictive validity as models of the disease and their reliability in recapitulating HD symptoms. OBJECTIVE: Manifest HD is currently diagnosed upon the onset of motor symptoms, thus we sought to longitudinally characterise the progression and severity of motor signs in the HdhQ111 knock-in mouse model of HD, in heterozygous mice. METHODS: An extensive battery of motor tests including: rotarod, inverted lid test, balance beam, spontaneous locomotor activity and gait analysis were applied longitudinally to a cohort of HdhQ111 heterozygous mice in order to progressively assess motor function. RESULTS: A progressive failure to gain body weight was demonstrated from 11 months of age and motor problems in all measures of balance beam performance were shown in HdhQ111 heterozygous animals in comparison to wild type control animals from 9 months of age. A decreased latency to fall from the rotarod was demonstrated in HdhQ111 heterozygous animals in comparison to wild type animals, although this was not progressive with time. No genotype specific differences were demonstrated in any of the other motor tests included in the test battery. CONCLUSIONS: The HdhQ111 heterozygous mouse demonstrates a subtle and progressive motor phenotype that begins at 9 months of age. This mouse model represents an early disease stage and would be ideal for testing therapeutic strategies that require elongated lead-in times, such as viral gene therapies or striatal transplantation. PMID- 27258588 TI - Variation in seizure prophylaxis in severe pediatric traumatic brain injury. AB - OBJECTIVE Posttraumatic seizure is a major complication following traumatic brain injury (TBI). The aim of this study was to determine the variation in seizure prophylaxis in select pediatric trauma centers. The authors hypothesized that there would be wide variation in seizure prophylaxis selection and use, within and between pediatric trauma centers. METHODS In this retrospective multicenter cohort study including 5 regional pediatric trauma centers affiliated with academic medical centers, the authors examined data from 236 children (age < 18 years) with severe TBI (admission Glasgow Coma Scale score <= 8, ICD-9 diagnosis codes of 800.0-801.9, 803.0-804.9, 850.0-854.1, 959.01, 950.1-950.3, 995.55, maximum head Abbreviated Injury Scale score >= 3) who received tracheal intubation for >= 48 hours in the ICU between 2007 and 2011. RESULTS Of 236 patients, 187 (79%) received seizure prophylaxis. In 2 of the 5 centers, 100% of the patients received seizure prophylaxis medication. Use of seizure prophylaxis was associated with younger patient age (p < 0.001), inflicted TBI (p < 0.001), subdural hematoma (p = 0.02), cerebral infarction (p < 0.001), and use of electroencephalography (p = 0.023), but not higher Injury Severity Score. In 63% cases in which seizure prophylaxis was used, the patients were given the first medication within 24 hours of injury, and 50% of the patients received the first dose in the prehospital or emergency department setting. Initial seizure prophylaxis was most commonly with fosphenytoin (47%), followed by phenytoin (40%). CONCLUSIONS While fosphenytoin was the most commonly used medication for seizure prophylaxis, there was large variation within and between trauma centers with respect to timing and choice of seizure prophylaxis in severe pediatric TBI. The heterogeneity in seizure prophylaxis use may explain the previously observed lack of relationship between seizure prophylaxis and outcomes. PMID- 27258589 TI - Massive sialadenitis resulting in critical airway after elective craniotomy: case report. AB - The authors report an unusual case of acute, rapidly progressive, unilateral neck swelling following extubation after elective left anterior temporal lobectomy with amygdalohippocampectomy. Due to severe neck swelling, the patient developed critical airway compromise, brachial plexopathy, and Horner's syndrome. After critical airway management and appropriate rehabilitation, the patient recovered completely and remains seizure free at 1.5 years of follow-up. This case highlights the importance of early recognition of acute postoperative sialadenitis and the steps needed to prevent serious morbidity and possible mortality from this rare complication. PMID- 27258590 TI - Long-tunnelled external ventricular drain as a long-term treatment option for hydrocephalus in a child with an unresectable low-grade supratentorial tumor: case report. AB - The authors report a case of a child with hypothalamic-origin pilocytic astrocytoma and hydrocephalus, which was refractory to treatment with a ventriculoperitoneal shunt due to high CSF protein content. With parental education, the child's hydrocephalus was managed long-term in the community with a long-tunnelled external ventricular drain, which was maintained by his parents. To the authors' knowledge this is the first report of this management option as a long-term measure. No harm has come to the patient. The authors propose long term, long-tunnelled external ventricular drain as a viable treatment option for such patients. PMID- 27258591 TI - Thirty-day outcomes after postnatal myelomeningocele repair: a National Surgical Quality Improvement Program Pediatric database analysis. AB - OBJECTIVE Due to improved nutrition and early detection, myelomeningocele repair is a relatively uncommon procedure. Although previous studies have reviewed surgical trends and predictors of outcomes, they have relied largely on single hospital experiences or on databases centered on hospital admission data. Here, the authors report 30-day outcomes of pediatric patients undergoing postnatal myelomeningocele repair from a national prospective surgical outcomes database. They sought to investigate the association between preoperative and intraoperative factors on the occurrence of 30-day complications, readmissions, and unplanned return to operating room events. METHODS The 2013 American College of Surgeons National Surgical Quality Improvement Program Pediatric database (NSQIP-P) was queried for all patients undergoing postnatal myelomeningocele repair. Patients were subdivided on the basis of the size of the repair (< 5 cm vs > 5 cm). Preoperative variables, intraoperative characteristics, and postoperative 30-day events were tabulated from prospectively collected data. Three separate outcomes for complication, unplanned readmission, and return to the operating room were analyzed using univariate and multivariate logistic regression. Rates of associated CSF diversion operations and their timing were also analyzed. RESULTS A total of 114 patients were included; 54 had myelomeningocele repair for a defect size smaller than 5 cm, and 60 had repair for a defect size larger than 5 cm. CSF shunts were placed concurrently in 8% of the cases. There were 42 NSQIP-defined complications in 31 patients (27%); these included wound complications and infections, in addition to others. Postoperative wound complications were the most common and occurred in 27 patients (24%). Forty patients (35%) had at least one subsequent surgery within 30 days. Twenty-four patients (21%) returned to the operating room for initial shunt placement. Unplanned readmission occurred in 11% of cases. Both complication and return to operating room outcomes were statistically associated with age at repair. CONCLUSIONS The NSQIP-P allows examination of 30-day perioperative outcomes from a national prospectively collected database. In this cohort, over one-quarter of patients undergoing postnatal myelomeningocele repair experienced a complication within 30 days. The complication rate was significantly higher in patients who had surgical repair within the first 24 hours of birth than in patients who had surgery after the 1st day of life. The authors also highlight limitations of investigating myelomeningocele repair using NSQIP-P and advocate the importance of disease-specific data collection. PMID- 27258592 TI - Editorial: Does it pass the sniff test? Mining the NSQIP-P database for neurosurgical diseases. PMID- 27258593 TI - Endoscopic third ventriculostomy in children: prospective, multicenter results from the Hydrocephalus Clinical Research Network. AB - OBJECTIVE Endoscopic third ventriculostomy (ETV) is now established as a viable treatment option for a subgroup of children with hydrocephalus. Here, the authors report prospective, multicenter results from the Hydrocephalus Clinical Research Network (HCRN) to provide the most accurate determination of morbidity, complication incidence, and efficacy of ETV in children and to determine if intraoperative predictors of ETV success add substantially to preoperative predictors. METHODS All children undergoing a first ETV (without choroid plexus cauterization) at 1 of 7 HCRN centers up to June 2013 were included in the study and followed up for a minimum of 18 months. Data, including detailed intraoperative data, were prospectively collected as part of the HCRN's Core Data Project and included details of patient characteristics, ETV failure (need for repeat hydrocephalus surgery), and, in a subset of patients, postoperative complications up to the time of discharge. RESULTS Three hundred thirty-six eligible children underwent initial ETV, 18.8% of whom had undergone shunt placement prior to the ETV. The median age at ETV was 6.9 years (IQR 1.7-12.6), with 15.2% of the study cohort younger than 12 months of age. The most common etiologies were aqueductal stenosis (24.8%) and midbrain or tectal lesions (21.2%). Visible forniceal injury (16.6%) was more common than previously reported, whereas severe bleeding (1.8%), thalamic contusion (1.8%), venous injury (1.5%), hypothalamic contusion (1.5%), and major arterial injury (0.3%) were rare. The most common postoperative complications were CSF leak (4.4%), hyponatremia (3.9%), and pseudomeningocele (3.9%). New neurological deficit occurred in 1.5% cases, with 0.5% being permanent. One hundred forty-one patients had documented failure of their ETV requiring repeat hydrocephalus surgery during follow-up, 117 of them during the first 6 months postprocedure. Kaplan-Meier rates of 30-day, 90-day, 6-month, 1-year, and 2-year failure-free survival were 73.7%, 66.7%, 64.8%, 61.7%, and 57.8%, respectively. According to multivariate modeling, the preoperative ETV Success Score (ETVSS) was associated with ETV success (p < 0.001), as was the intraoperative ability to visualize a "naked" basilar artery (p = 0.023). CONCLUSIONS The authors' documented experience represents the most detailed account of ETV results in North America and provides the most accurate picture to date of ETV success and complications, based on contemporaneously collected prospective data. Serious complications with ETV are low. In addition to the ETVSS, visualization of a naked basilar artery is predictive of ETV success. PMID- 27258594 TI - Mobile spinal enterogenous cyst resulting in intermittent paraplegia in a child: case report. AB - The authors report the case of a mobile spinal enterogenous cyst in a 2-year-old boy, who was admitted to the hospital several times for intermittent paraplegia. Magnetic resonance imaging and CT revealed an isolated cyst in the lumbar spinal canal. The symptoms were caused by transient myelopathy of the conus medullaris and radiculopathy of the cauda equina due to the changing size and location of the cyst. The cyst was surgically extirpated, after which the symptoms resolved. The histopathological diagnosis was enterogenous cyst. The clinical history of intraspinal enterogenous cyst is usually progressive. Mobility and changes in size are rare pathophysiological findings. The authors speculate that the cyst wall did not adhere to the surrounding structures and had ruptured and quickly reformed. Enterogenous cyst should be considered in the differential diagnosis of spinal intradural cysts in children with radiculomyelopathy. PMID- 27258596 TI - Risk factors and visual fatigue of baggage X-ray security screeners: a structural equation modelling analysis. AB - This study identified the risk factors influencing visual fatigue in baggage X ray security screeners and estimated the strength of correlations between those factors and visual fatigue using structural equation modelling approach. Two hundred and five X-ray security screeners participated in a questionnaire survey. The result showed that satisfaction with the VDT's physical features and the work environment conditions were negatively correlated with the intensity of visual fatigue, whereas job stress and job burnout had direct positive influences. The path coefficient between the image quality of VDT and visual fatigue was not significant. The total effects of job burnout, job stress, the VDT's physical features and the work environment conditions on visual fatigue were 0.471, 0.469, -0.268 and -0.251 respectively. These findings indicated that both extrinsic factors relating to VDT and workplace environment and psychological factors including job burnout and job stress should be considered in the workplace design and work organisation of security screening tasks to reduce screeners' visual fatigue. Practitioner Summary: This study identified the risk factors influencing visual fatigue in baggage X-ray security screeners and estimated the strength of correlations between those factors and visual fatigue. The findings were of great importance to the workplace design and the work organisation of security screening tasks to reduce screeners' visual fatigue. PMID- 27258595 TI - An observational study of child safety seat use in an international safe community: Tehran, Iran. AB - OBJECTIVE: Despite strong evidence of the effectiveness of child safety seats in reducing injuries, the use of these devices in some communities is still rare. The purpose of this study was to determine the prevalence of child safety seat use and the factors influencing its use in the safe community of Tehran. METHODS: This roadside observational study was conducted in 2015 and 2,178 personal cars with a child under 12 years aboard were observed on Tehran's streets in regard to use of child safety seats. Other variables such as the gender of the driver, driver's age group, type of street, region of municipality, time of day, and day of the week were also collected. RESULTS: Prevalence of child safety seat use was 4.3% and was significantly higher among women drivers, on freeways, and in municipal regions 1, 4, and 7. CONCLUSIONS: The prevalence of child safety seat use in Tehran as a most populous member of the international safe community was very low and most children commuted in insecure situations in the vehicle. Therefore, it is proposed that plans should be made to increase the use of child safety seats in international safe communities. PMID- 27258597 TI - Nickel-Catalyzed Decarbonylative Borylation of Amides: Evidence for Acyl C-N Bond Activation. AB - A nickel/N-heterocyclic carbene catalytic system has been established for decarbonylative borylation of amides with B2 nep2 by C-N bond activation. This transformation shows good functional-group compatibility and can serve as a powerful synthetic tool for late-stage borylation of amide groups in complex compounds. More importantly, as a key intermediate, the structure of an acyl nickel complex was first confirmed by X-ray analysis. Furthermore, the decarbonylative process was also observed. These findings confirm the key mechanistic features of the acyl C-N bond activation process. PMID- 27258598 TI - Temperature Variability and Mortality: A Multi-Country Study. AB - BACKGROUND: The evidence and method are limited for the associations between mortality and temperature variability (TV) within or between days. OBJECTIVES: We developed a novel method to calculate TV and investigated TV-mortality associations using a large multicountry data set. METHODS: We collected daily data for temperature and mortality from 372 locations in 12 countries/regions (Australia, Brazil, Canada, China, Japan, Moldova, South Korea, Spain, Taiwan, Thailand, the United Kingdom, and the United States). We calculated TV from the standard deviation of the minimum and maximum temperatures during the exposure days. Two-stage analyses were used to assess the relationship between TV and mortality. In the first stage, a Poisson regression model allowing over dispersion was used to estimate the community-specific TV-mortality relationship, after controlling for potential confounders. In the second stage, a meta-analysis was used to pool the effect estimates within each country. RESULTS: There was a significant association between TV and mortality in all countries, even after controlling for the effects of daily mean temperature. In stratified analyses, TV was still significantly associated with mortality in cold, hot, and moderate seasons. Mortality risks related to TV were higher in hot areas than in cold areas when using short TV exposures (0-1 days), whereas TV-related mortality risks were higher in moderate areas than in cold and hot areas when using longer TV exposures (0-7 days). CONCLUSIONS: The results indicate that more attention should be paid to unstable weather conditions in order to protect health. These findings may have implications for developing public health policies to manage health risks of climate change. CITATION: Guo Y, Gasparrini A, Armstrong BG, Tawatsupa B, Tobias A, Lavigne E, Coelho MS, Pan X, Kim H, Hashizume M, Honda Y, Guo YL, Wu CF, Zanobetti A, Schwartz JD, Bell ML, Overcenco A, Punnasiri K, Li S, Tian L, Saldiva P, Williams G, Tong S. 2016. Temperature variability and mortality: a multi-country study. Environ Health Perspect 124:1554-1559; http://dx.doi.org/10.1289/EHP149. PMID- 27258599 TI - Origin of Multiple Formula Use to Calculate Intraocular Lens Power. PMID- 27258600 TI - Simultaneous Median-Radial Nerve Electrical Stimulation Revisited: An Accurate Approach to Carpal Tunnel Syndrome Diagnosis and Severity. AB - PURPOSE: To assess the accuracy of an unusual test for CTS investigation and correlate it with clinical symptoms. METHODS: Initially, we applied a visual analog scale for CTS discomfort (CTS-VAS) and performed a standard electrophysiologic test for CTS diagnosis (median-ulnar velocity comparison). Posteriorly, a blinded neurophysiologist performed the orthodromic simultaneous median-radial nerve stimulation (SMRS) at the thumb, with recording of both action potentials over the lateral aspect of the wrist. RESULTS: All hands (106) showed median-radial action potential splitting using the SMRS technique, in which was possible to measure the interpeak latencies (IPLs) between action potentials. The IPL and median nerve conduction velocity were different according to CTS intensity (Bonferroni; P < 0.001). There was significant correlation between IPL and median nerve conduction velocity (Spearman; r = -0.51; P < 0.01). In the same way, there was a significant correlation between IPL and median nerve conduction velocity with CTS-VAS (r = 0.6 and r = -0.3, respectively). The duration and unpleasantness of the SMRS procedure were lower when compared with standard approach (t Student < 0.001 for both comparisons). Twenty-nine symptomatic patients (39 hands) who did not fulfill criteria for CTS based on standard approach showed abnormal IPLs. CONCLUSIONS: The SMRS technique is a simple, sensitive, and tolerable approach for CTS diagnosis. Apart from that, the data from SMRS correlated better with clinical impact of CTS in comparison with the standard approach. Therefore, this method might be useful as adjunct to standard electrophysiologic approaches in clinical practice. PMID- 27258601 TI - Therapeutic Implications of Peripheral Nerve Hyperexcitability in Muscle Cramping: A Retrospective Review. AB - PURPOSE: Muscle cramping due to peripheral nerve hyperexcitability (PNH) is poorly characterized. This retrospective study examines the prevalence of PNH and response to treatment. METHODS: The Duke EMG Database was queried to identify patients with muscle cramping tested for PNH from 2010 to 2015. Peripheral nerve hyperexcitability was defined by compound muscle action potential after discharges on repetitive nerve stimulation. Response to treatment was determined by the treating physician's clinical impression 6 months after diagnosis or last documented visit. RESULTS: Seventy-two patients met inclusion criteria. Twenty three (32%) patients had electrodiagnostic evidence of PNH. Of the patients with PNH, 74% had a good response to treatment whereas 37% of treated patients in the PNH-negative group (P = 0.0258). Carbamazepine and gabapentin were the most frequently used treatments with response rates of 70% and 77%, respectively. CONCLUSION: Muscle cramps associated with PNH respond well to symptomatic treatment, particularly with carbamazepine and gabapentin. PMID- 27258602 TI - Subcutaneous Dupilumab and Mometasone Furoate Nasal Spray for Chronic Rhinosinusitis With Polyps. PMID- 27258605 TI - Megalopapilla Simulating Pediatric Optic Atrophy. PMID- 27258606 TI - Optical Coherence Tomography of Cavitary Retinoblastoma. PMID- 27258607 TI - Visualization of a Hematoma of the Cloquet Canal. PMID- 27258608 TI - Simultaneous Retinal and Choroidal Metastases in Lung Adenocarcinoma. PMID- 27258609 TI - Allopurinol decreases serum uric acid level and intestinal glucose transporter-5 expression in rats with fructose-induced hyperuricemia. AB - BACKGROUND: High fructose consumption is considered to be related to the increasing prevalence of hyperuricemia (HUA). Glucose transporters (GLUT) 2 and 5 are crucial for fructose absorption and transporter. Effects of anti-HUA drugs, allopurinol (API) and benzbromarone (BBR), on expressions of GLUT5 and GLUT2 are not evaluated. METHOD: Wistar rats were given 10% fructose in drinking water for 60 days to induce HUA, and 5mg/kg API and 10mg/kg BBR were intragastricly treated for 30 days. Serum level of uric acid and xanthine oxidase (XOD) activity in liver were determined. Expressions of GLUT2 and GLUT5 in intestine were analyzed by immunohistochemistry staining assay and Western blot assay. RESULTS: Treatment with API or BBR significantly decreased the serum level of uric acid in HUA rats induced by fructose. Meanwhile, API treatment significantly reduced the XOD activity in liver and GLUT5 expression in intestine. However, BBR treatment did not show inhibitory effects on hepatic XOD activity and intestinal GLUT5 expression. In addition, treatment with API or BBR did not show any effect on GLUT2 expression in intestine. CONCLUSION: API decreases serum level of uric acid in fructose-induced HUA rats. The mechanisms are associated with suppressing XOD activity in liver to reduce uric acid production, and inhibiting GLUT5 expression in intestine to reduce fructose absorption. PMID- 27258610 TI - 3R gene expression in chronic lymphocytic leukemia reveals insight into disease evolution. PMID- 27258611 TI - Improved anti-leukemia activities of adoptively transferred T cells expressing bispecific T-cell engager in mice. AB - Despite the impressive clinical efficacy of T cells engineered to express chimeric antigen receptors (CAR-Ts), the current applications of CAR-T cell therapy are limited by major treatment-related toxicity. Thus, safer yet effective alternative approaches must be developed. In this study, we compared CD19 bispecific T-cell engager (BiTE)-transferred T cells that had been transfected by RNA electroporation with CD19 CAR RNA-transferred T cells both in vitro and in an aggressive Nalm6 leukemia mouse model. BiTEs were secreted from the transferred T cells and enabled both the transferred and bystander T cells to specifically recognize CD19(+) cell lines, with increased tumor killing ability, prolonged functional persistence, increased cytokine production and potent proliferation compared with the CAR-T cells. More interestingly, in comparison with CD3/CD28 bead-stimulated T cells, T cells that were expanded by a rapid T cell expansion protocol (REP) showed enhanced anti-tumor activities for both CAR and BiTE RNA-electroporated T cells both in vitro and in a Nalm6 mouse model (P<0.01). Furthermore, the REP T cells with BiTE RNAs showed greater efficacy in the Nalm6 leukemia model compared with REP T cells with CAR RNA (P<0.05) and resulted in complete leukemia remission. PMID- 27258613 TI - Experiment With Management, not Reimbursement. PMID- 27258612 TI - Transcriptome analysis of G protein-coupled receptors in distinct genetic subgroups of acute myeloid leukemia: identification of potential disease-specific targets. AB - Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups. PMID- 27258614 TI - Protective efficacy of a recombinant bacterial artificial chromosome clone of a very virulent Marek's disease virus containing a reticuloendotheliosis virus long terminal repeat. AB - Marek's disease virus (MDV), an alphaherpesvirus, causes Marek's disease (MD), a lymphoproliferative disease in poultry characterized by T-cell lymphomas, nerve lesions, and mortality. Vaccination is used worldwide to control MD, but increasingly virulent field strains can overcome this protection, driving a need to create new vaccines. Previous studies revealed that insertion of reticuloendotheliosis virus (REV) long terminal repeat (LTR) into a bacterial artificial chromosome (BAC) clone of a very virulent strain of MDV, Md5, rendered the resultant recombinant virus, rMd5 REV-LTR BAC, fully attenuated in maternal antibody positive (Mab+) chickens at passage 40. In the current study, the protective efficacy of rMd5 REV-LTR BAC was evaluated. First, passage 70 was identified as being fully attenuated in maternal antibody negative chickens and chosen as the optimal passage level for use in protective efficacy studies. Second, three protective efficacy trials were conducted comparing the rMd5 REV LTR p70 BAC to the CVI988/Rispens vaccine. Groups of Mab+ and Mab- 15I5 * 71 chickens were vaccinated in ovo at 18 days of embryonation or intra-abdominally at day of hatch, and challenged at 5 days post-hatch with the vv+MDV strain 686. Vaccination at day of hatch and in ovo with rMd5 REV-LTR p70 BAC protected chickens against MDV-induced bursa and thymic atrophy, but did not provide the same level of protection against MD tumours as that afforded by the commercial vaccine, CVI988/Rispens. PMID- 27258615 TI - Lollipop-induced oral lichenoid reaction in a child. AB - BACKGROUND: Oral lichenoid reactions (OLRs) have been rarely reported in pediatric patients. CASE REPORT: This article reports an unusual case of a 15 year-old girl who had white plaques in tongue and buccal mucosa oral which initially were diagnosed as oral lichen planus (OLP). At first, the patient and her family denied systemic or local medication use. Biopsy was performed, and histopathological aspects were suggestive of OLP. Despite the attempt of treatment with topical corticoid, the lesions did not recede. Patient's behavior and medical history were again investigated and revealed that she had been using almost daily in her school an artificially colored and flavored lollipop. One week after removing lollipop use behavior, the oral lesions showed complete resolution and OLR diagnosis was defined. CONCLUSION: The present case denotes that OLR should be considered in the differential diagnosis of oral white plates in children and artificially colored sweets can be its causal agent. PMID- 27258616 TI - A full evaluation for the enantiomeric impacts of lactofen and its metabolites on aquatic macrophyte Lemna minor. AB - Pesticide pollution of surface water represents a considerable danger for the aquatic plants which play very crucial roles in aquatic system such as oxygen production, nutrient cycling, water quality controlling and sediment stabilization. In this work, the toxic effects of the chiral herbicide lactofen and its three metabolites (desethyl lactofen, acifluorfene and amino acifluorfene) to the aquatic plant Lemna minor (L. minor) on enantiomeric level were evaluated. The influences on growth rate, fresh weight, content of photosynthetic pigment, protein and malondialdehyde (MDA) and the activities of antioxidant defense enzymes (catalase (CAT) and superoxide dismutase (SOD)) were measured after 7 days of exposure. L. minor growth was inhibited in the order of (S)-desethyl lactofen > racemic-desethyl lactofen > (R)-desethyl lactofen > racemic-lactofen > (S)-lactofen > (R)-lactofen > acifluorfene > amino acifluorfene, and the IC50 (7d) values showed desethyl lactofen was the most powerful compound which was about twice as toxic as lactofen. The contents of chlorophylls (Chl) and carotenoids (Car) were significantly reduced by the chemicals, while, the levels of protein, MDA and the activity of CAT and SOD enzymes increased in most cases. The obtained results revealed that lactofen and its metabolites had an undesirable effect on L. minor, in terms of physiological and biochemical aspects. Besides, enantioselective toxicity of lactofen and desethyl lactofen to L. minor was observed. The S-enantiomer of desethyl lactofen was more toxic than the corresponding R-enantiomer. Furthermore, racemic lactofen was more toxic than the individual enantiomers. The side effects of pesticide metabolites and the enantioselectivity should be considered in developing optically pure products and risk assessment. PMID- 27258617 TI - Greenhouse gas emissions from waste stabilisation ponds in Western Australia and Quebec (Canada). AB - Waste stabilisation ponds (WSPs) are highly enriched environments that may emit large quantities of greenhouse gases (GHG), including CO2, CH4 and N2O. However, few studies provide detailed reports on these emissions. In the present study, we investigated GHG emissions from WSPs in Western Australia and Quebec, Canada, and compared emissions to WSPs from other climatic regions and to other types of aquatic ecosystems. Surface water GHG concentrations were related to phytoplankton biomass and nutrients. The CO2 was either emitted or absorbed by WSPs, largely as a function of phytoplankton dynamics and strong stratification in these shallow systems, whereas efflux of CH4 and N2O to the atmosphere was always observed albeit with highly variable emission rates, dependent on treatment phase and time of the day. The total global warming potential index (GWP index, calculated as CO2 equivalent) of emitted GHG from WSPs in Western Australia averaged 12.8 mmol m(-2) d(-1) (median), with CO2, CH4 and N2O respectively contributing 0%, 96.7% and 3.3% of the total emissions, while in Quebec WSPs this index was 194 mmol m(-2) d(-1), with a relative contribution of 93.8, 3.0 and 3.2% respectively. The CO2 fluxes from WSPs were of the same order of magnitude as those reported in hydroelectric reservoirs and constructed wetlands in tropical climates, whereas CH4 fluxes were considerably higher compared to other aquatic ecosystems. N2O fluxes were in the same range of values reported for WSPs in subtropical climate. PMID- 27258618 TI - Optimal flow sensor placement on wastewater treatment plants. AB - Obtaining high quality data collected on wastewater treatment plants is gaining increasing attention in the wastewater engineering literature. Typical studies focus on recognition of faulty data with a given set of installed sensors on a wastewater treatment plant. Little attention is however given to how one can install sensors in such a way that fault detection and identification can be improved. In this work, we develop a method to obtain Pareto optimal sensor layouts in terms of cost, observability, and redundancy. Most importantly, the resulting method allows reducing the large set of possibilities to a minimal set of sensor layouts efficiently for any wastewater treatment plant on the basis of structural criteria only, with limited sensor information, and without prior data collection. In addition, the developed optimization scheme is fast. Practically important is that the number of sensors needed for both observability of all flows and redundancy of all flow sensors is only one more compared to the number of sensors needed for observability of all flows in the studied wastewater treatment plant configurations. PMID- 27258619 TI - Evaluation of virus removal efficiency of coagulation-sedimentation and rapid sand filtration processes in a drinking water treatment plant in Bangkok, Thailand. AB - In order to properly assess and manage the risk of infection by enteric viruses in tap water, virus removal efficiency should be evaluated quantitatively for individual processes in actual drinking water treatment plants (DWTPs); however, there have been only a few studies due to technical difficulties in quantifying low virus concentration in water samples. In this study, the removal efficiency of indigenous viruses was evaluated for coagulation-sedimentation (CS) and rapid sand filtration (RSF) processes in a DWTP in Bangkok, Thailand by measuring the concentration of viruses before and after treatment processes using real-time polymerase chain reaction (qPCR). Water samples were collected and concentrated from raw source water, after CS, and after RSF, and inhibitory substances in water samples were reduced by use of a hydrophobic resin (DAX-8). Pepper mild mottle virus (PMMoV) and JC polyomavirus (JC PyV) were found to be highly prevalent in raw waters, with concentrations of 10(2.88 +/- 0.35) and 10(3.06 +/- 0.42) copies/L (geometric mean +/- S.D.), respectively. Step-wise removal efficiencies were calculated for individual processes, with some variation observed between wet and dry seasons. During the wet season, PMMoV was removed less by CS and more by RSF on average (0.40 log10 vs 1.26 log10, respectively), while the reverse was true for JC PyV (1.91 log10 vs 0.49 log10, respectively). Both viruses were removed similarly during the dry season, with CS removing the most virus (PMMoV, 1.61 log10 and 0.78 log10; JC PyV, 1.70 log10, and 0.59 log10; CS and RSF, respectively). These differences between seasons were potentially due to variations in raw water quality and the characteristics of the viruses themselves. These results suggest that PMMoV and JC PyV, which are more prevalent in environmental waters than the other enteric viruses evaluated in this study, could be useful in determining viral fate for the risk management of viruses in water treatment processes in actual full-scale DWTPs. PMID- 27258620 TI - Transformation of avobenzone in conditions of aquatic chlorination and UV irradiation. AB - Emerging contaminants represent a wide group of the most different compounds. They appear in the environment at trace levels due to human activity. Most of these compounds are not yet regulated. Sunscreen UV-filters play an important role among these emerging contaminants. In the present research the reactions of 4-tert-butyl-4'-methoxydibenzoylmethane (avobenzone), the most common UV filter in the formulation of sunscreens, were studied under the combined influence of active chlorine and UV-irradiation. Twenty five compounds were identified by GC/MS as transformation products of avobenzone in reactions of aquatic UV irradiation and chlorination with sodium hypochlorite. A complete scheme of transformation of avobenzone covering all the semivolatile products is proposed. The identification of the two primary chlorination products (2-chloro-1-(4-tert butylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione and 2,2-dichloro-1-(4-tert butylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione) was confirmed by their synthesis and GC/MS and NMR analysis. Although the toxicities of the majority of these products remain unknown substituted chlorinated phenols and acetophenones are known to be rather toxic. Combined action of active chlorine and UV irradiation results in the formation of some products (chloroanhydrides, chlorophenols) not forming in conditions of separate application of these disinfection methods. Therefore caring for people "well-being" it is of great importance to apply the most appropriate disinfection method. Since the primary transformation products partially resist powerful UV-C irradiation they may be treated as stable and persistent pollutants. PMID- 27258621 TI - Formic acid enhanced effective degradation of methyl orange dye in aqueous solutions under UV-Vis irradiation. AB - Developing efficient technologies to treat recalcitrant organic dye wastewater has long been of great research and practical interest. In this study, a small molecule, formic acid (FA), was applied as a process enhancer for the degradation of methyl orange (MO) dye as a model recalcitrant organic pollutant in aqueous solutions under the condition of UV-Vis light irradiation and air aeration at the ambient temperature of 25 degrees C. It was found that the decolouration of the dye solutions can be rapidly achieved, reducing the time, for example, from around 17.6 h without FA to mostly about less than 2 h with the presence of FA. The mineralization rate of MO dye reached as high as 81.8% in 1.5 h in the case of initial MO dye concentration at 25 mg L(-1), which is in contrast to nearly no mineralization of the MO dye for a similar system without the FA added. The study revealed that the generation of the H2O2 species in the system was enhanced and the produced OH radicals effectively contributed to the degradation of the MO dye. Process parameters such as the initial concentration of MO dye, FA dosage and solution pH were all found to have some effect on the degradation efficiency under the same condition of UV-Vis light irradiation and air aeration. The MO dye degradation performance was found to follow a first-order reaction rate to the MO dye concentration in most cases and there existed a positive correlation between the reaction rate constant and the initial FA concentration. Compared to the traditional H2O2/UV-Vis oxidation system, the use of FA as a process-enhancing agent can have the advantages of low cost, easy availability, and safe to use. The study hence demonstrates a promising approach to use a readily available small molecule of FA to enhance the degradation of recalcitrant organic pollutants, such as MO dye, especially for their pre-treatment. PMID- 27258622 TI - Novel c-Met inhibitory olive secoiridoid semisynthetic analogs for the control of invasive breast cancer. AB - Dysregulated receptor tyrosine kinase c-Met and its ligand HGF is valid and attractive molecular target for therapeutic blockade in cancer. Inspired by the chemical structure of the naturally occurring olive secoiridoid (-)-oleocanthal (1) and its documented anticancer activity against c-Met-dependent malignancies, a previous study reported tyrosol sinapate (4) as a c-Met inhibitor hit. This study reports additional semisynthetic optimization and SAR of 4 to improve its selective activity against c-Met-dependent breast cancer by increasing its capacity to inhibit c-Met phosphorylation. Forty-three compounds (5-47) were synthesized, among which the novel analog homovanillyl sinapate (HVS-16) was distinguished for its remarkable activity. HVS-16 substantially impaired c-Met mediated proliferation, migration, and invasion across human breast cancer cell lines in two- and three-dimensional culture systems, while similar treatment doses were found to have effect neither on the non-tumorigenic human mammary epithelial cell growth nor on the c-Met independent breast cancer cell viability. HVS-16 showed a dose-dependent inhibition of ligand-mediated c-Met activation in human breast cancer cells. Docking studies revealed that HVS-16 fits very well inside c-Met crystal structures, satisfying critical interactions at the ATP binding site. This study identified important structural pharmacophoric features in HVS-16 and correlated its postulated binding pose with c-Met kinase assay data that would guide future olive secoiridoid bioisostere lead design. Results presented herein suggest HVS-16 as a promising c-Met inhibitor validated hit with potential to control invasive breast malignancies with aberrant c-Met activity. PMID- 27258623 TI - Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts. AB - BACKGROUND: Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. OBJECTIVES: To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. METHODS: We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). RESULTS: There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0.6, 95% confidence interval 0.5-0.7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0.54, 95% confidence interval 0.47-0.61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. CONCLUSIONS: Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases. PMID- 27258625 TI - Azomethine Ylides from Nitrones: Using Catalytic nBuLi for the Totally Stereoselective Synthesis of trans-2-Alkyl-3-oxazolines. AB - The cycloaddition of azomethine ylide N-oxides (nitrone ylides) with aldehydes provides 3-oxazolines in a completely stereoselective manner in the presence of a catalytic amount of n-butyllithium. The process involves an initial nucleophilic attack on the aldehyde, followed by intramolecular oxygen addition to the nitrone moiety and lithium-assisted elimination of water, regenerating the catalytic species. Various Li-based catalytic systems are possible and the in situ generated water is required for continuing the catalytic cycle. The best results are observed with 20 mol % of n-butyllithium, whereas the use of stoichiometric amounts inhibit the rate of catalysis. Experimental, spectroscopic, and computational mechanistic studies have provided evidence of lithium-ion catalysis and rationalized several competing catalytic pathways. PMID- 27258624 TI - Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons. AB - PURPOSE: To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. MATERIALS AND METHODS: We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. RESULTS: HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. CONCLUSIONS: Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation. PMID- 27258626 TI - A Chiral Thiourea as a Template for Enantioselective Intramolecular [2 + 2] Photocycloaddition Reactions. AB - A chiral (1R,2R)-diaminocyclohexane-derived bisthiourea was found to exhibit a significant asymmetric induction in the intramolecular [2 + 2] photocycloaddition of 2,3-dihydropyridone-5-carboxylates. Under optimized conditions, the reaction was performed with visible light employing 10 mol % of thioxanthone as triplet sensitizer. Due to the different electronic properties of its carbonyl oxygen atoms, a directed binding of the substrate to the template is possible, which in turn enables an efficient enantioface differentiation. PMID- 27258644 TI - Fungal meningitis caused by Lomentospora prolificans after allogeneic hematopoietic stem cell transplantation. AB - Central nervous system lomentosporiosis is a rare pathological condition in immunocompromised patients. We describe a fatal case of meningitis caused by Lomentospora prolificans (which was previously named Scedosporium prolificans), after an allogeneic hematopoietic stem cell transplantation (allo-HSCT). To our knowledge, no cases of Lomentospora meningitis following allo-HSCT have been reported previously. Particularly in neutropenic patients, it is important to consider L. prolificans when a fungal infection is suspected and antifungal agents are ineffective. PMID- 27258645 TI - Quantitative atomic resolution elemental mapping via absolute-scale energy dispersive X-ray spectroscopy. AB - Quantitative agreement on an absolute scale is demonstrated between experiment and simulation for two-dimensional, atomic-resolution elemental mapping via energy dispersive X-ray spectroscopy. This requires all experimental parameters to be carefully characterized. The agreement is good, but some discrepancies remain. The most likely contributing factors are identified and discussed. Previous predictions that increasing the probe forming aperture helps to suppress the channelling enhancement in the average signal are confirmed experimentally. It is emphasized that simple column-by-column analysis requires a choice of sample thickness that compromises between being thick enough to yield a good signal-to-noise ratio while being thin enough that the overwhelming majority of the EDX signal derives from the column on which the probe is placed, despite strong electron scattering effects. PMID- 27258646 TI - CACNA1H(M1549V) Mutant Calcium Channel Causes Autonomous Aldosterone Production in HAC15 Cells and Is Inhibited by Mibefradil. AB - We recently demonstrated that a recurrent gain-of-function mutation in a T-type calcium channel, CACNA1H(M1549V), causes a novel Mendelian disorder featuring early-onset primary aldosteronism and hypertension. This variant was found independently in five families. CACNA1H(M1549V) leads to impaired channel inactivation and activation at more hyperpolarized potentials, inferred to cause increased calcium entry. We here aimed to study the effect of this variant on aldosterone production. We heterologously expressed empty vector, CACNA1H(WT) and CACNA1H(M1549V) in the aldosterone-producing adrenocortical cancer cell line H295R and its subclone HAC15. Transfection rates, expression levels, and subcellular distribution of the channel were similar between CACNA1H(WT) and CACNA1H(M1549V). We measured aldosterone production by an ELISA and CYP11B2 (aldosterone synthase) expression by real-time PCR. In unstimulated cells, transfection of CACNA1H(WT) led to a 2-fold increase in aldosterone levels compared with vector-transfected cells. Expression of CACNA1H(M1549V) caused a 7 fold increase in aldosterone levels. Treatment with angiotensin II or increased extracellular potassium levels further stimulated aldosterone production in both CACNA1H(WT)- and CACNA1H(M1549V)-transfected cells. Similar results were obtained for CYP11B2 expression. Inhibition of CACNA1H channels with the T-type calcium channel blocker Mibefradil completely abrogated the effects of CACNA1H(WT) and CACNA1H(M1549V) on CYP11B2 expression. These results directly link CACNA1H(M1549V) to increased aldosterone production. They suggest that calcium channel blockers may be beneficial in the treatment of a subset of patients with primary aldosteronism. Such blockers could target CACNA1H or both CACNA1H and the L-type calcium channel CACNA1D that is also expressed in the adrenal gland and mutated in patients with primary aldosteronism. PMID- 27258647 TI - Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study. AB - OBJECTIVES: Definition of the optimal pneumococcal vaccine strategy in HIV infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) versus the 23 valent polysaccharide vaccine (PPSV23) in HIV-infected adults. METHODS: We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naive outpatients, aged 18-65 years with CD4 counts >=200 cells/MUL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50) received two doses of PCV13 eight weeks apart, and group 2 (n = 50) received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100) were also enrolled as baseline controls. RESULTS: Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group. CONCLUSIONS: In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02123433. PMID- 27258648 TI - The application of phospholipid removal columns and ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry for quantification of multi class antibiotics in aquaculture samples. AB - In this study a robust and sensitive method based on a proposed sample purification procedure, using zirconia-coated PhreeTM columns and analysis by ultra-high performance liquid chromatography with triple quadrupole tandem mass spectrometry are presented for the assessment of multi-class antibiotics in farmed fish species. The sample preparation procedure benefited from combined precipitation of proteins and selective removal of phospholipids by PhreeTM columns, resulting in a high sensitivity of the method (LOQ 0.3-9mgkg(-1)). The in-house validation results (precision, repeatability, decision limit CCalpha, detection capability CCbeta, etc.) indicate that the elaborated method is fully suitable for the analysis of the main classes of antibiotics in accordance with the European Union (EU) Commission Decision 2002/657/EC. The method was applied to the analysis of antibiotics in trout and sturgeon samples obtained from the local inland aquacultures in Latvia. The results revealed the presence of two antibiotics (enrofloxacin and trimethoprim) in 12 out of the 20 analysed fish samples at concentrations (0.33-12.2MUgkg(-1)) below the MRLs, thus causing no acute risks to consumers. PMID- 27258649 TI - Lifestyle and Socioeconomic Determinants of Multimorbidity Patterns among Mid Aged Women: A Longitudinal Study. AB - BACKGROUND: Little is known about patterns of associative multimorbidity and their aetiology. We aimed to identify patterns of associative multimorbidity among mid-aged women and the lifestyle and socioeconomic factors associated with their development. METHODS: Participants were from the Australian Longitudinal Study on Women's Health. We included 4896 women born 1946-51, without multimorbidity in 1998. We identified multimorbidity patterns at survey 6 (2010) using factor analysis, and related these patterns to baseline lifestyle and socioeconomic factors using logistic regression. We dichotomised factor scores and determined odds ratios (ORs) with 95% confidence intervals (CIs) for associations between characteristics and odds of a high versus low factor score. RESULTS: We identified five multimorbidity patterns: psychosomatic; musculoskeletal; cardiometabolic; cancer; and respiratory. Overweight and obesity were respectively associated with increased odds of having a high score for the musculoskeletal (adjusted ORs 1.45 [95% CI 1.23, 1.70] and 2.14 [95% CI 1.75, 2.60]) and cardiometabolic (adjusted ORs 1.53 [95% CI 1.31, 1.79] and 2.46 [95% CI 2.02, 2.98]) patterns. Physical inactivity was associated with increased odds of a high score for the psychosomatic, musculoskeletal and cancer patterns (adjusted ORs 1.41 [95% CI 1.13, 1.76]; 1.39 [95% CI 1.11, 1.74]; and 1.35 [95% CI 1.08, 1.69]). Smoking was associated with increased odds of a high score for the respiratory pattern. Education and ability to manage on income were associated with increased odds of a high score for the psychosomatic pattern (adjusted ORs 1.34 [95% CI 1.03, 1.75] and 1.73 [95% CI 1.37, 1.28], respectively) and musculoskeletal pattern (adjusted ORs 1.43 [95% CI 1.10, 1.87] and 1.38 [1.09, 1.75], respectively). CONCLUSIONS: Distinct multimorbidity patterns can be identified among mid-aged women. Social inequality, physical activity and BMI are risk factors common to multiple patterns and are appropriate targets for reducing the risk of specific multimorbidity groups in mid-life women. PMID- 27258650 TI - Reintroduction and Post-Release Survival of a Living Fossil: The Chinese Giant Salamander. AB - Captive rearing and reintroduction / translocation are increasingly used as tools to supplement wild populations of threatened species. Reintroducing captive reared Chinese giant salamanders may help to augment the declining wild populations and conserve this critically endangered amphibian. We released 31 captive-reared juvenile giant salamanders implanted with VHF radio transmitters at the Heihe River (n = 15) and the Donghe River (n = 16) in the Qinling Mountains of central China. Salamanders were monitored every day for survival from April 28th 2013 to September 3rd 2014. We attempted to recapture all living individuals by the end of the study, measured their body mass and total body length, and checked for abnormalities and presence of external parasites. Two salamanders at the Heihe River and 10 animals at the Donghe River survived through the project timeline. Nine salamanders were confirmed dead, while the status of the other 10 animals was undetermined. The annual survival rate of giant salamanders at the Donghe River (0.702) was 1.7-fold higher than that at the Heihe River (0.405). Survival increased as individuals were held longer following surgery, whereas body mass did not have a significant impact on survival rate. All salamanders recaptured from the Donghe River (n = 8) increased in mass (0.50 +/- 0.13 kg) and length (5.5 +/- 1.5 cm) after approximately 11 months in the wild, and they were only 7% lighter than wild animals of the same length (mean residual = -0.033 +/- 0.025). Our results indicate that captive reared Chinese giant salamanders can survive in the wild one year after release and adequate surgical recovery time is extremely important to post-release survival. Future projects may reintroduce older juveniles to achieve better survival and longer monitoring duration. PMID- 27258651 TI - Cardiovascular Outcomes Following Rotational Atherectomy: A UK Multicentre Experience. AB - OBJECTIVES: To identify factors associated with outcomes following rotational atherectomy (RA). BACKGROUND: RA is an effective way to mechanically modify heavily calcified lesions before stenting; however its outcomes are not well defined. METHODS AND RESULTS: Retrospective evaluation of all patients who underwent RA in three large UK centers (Leeds General Infirmary (LGI), Royal Infirmary of Edinburgh (RIE) and University Hospital of North Staffordshire (UHNS)) from March 2005 to January 2013. Five hundred and eighteen patients had RA with median follow-up period of 22 months. About 68.3% were male, 28.7% had DM and 34.6% were treated because of ACS. Stents were deployed in 97.3% of the patients while 30.7% of the procedures were performed transradially. Maximum burr was <=1.75 mm in 85.5% and the mean SYNTAX score was 19.5 +/- 11.6. Peri procedural complications occurred in 6.4% and vascular access complications in 1.9%. Outcomes in the follow-up period were: MACE 17.8%, cardiac death 7.1%, MI 11.7%, TVR 7.5%, all-cause death 13.7%, definite stent thrombosis (ST) 1.4% and stroke 2.9%. Patients with intermediate and high SYNTAX scores were more likely to suffer MACE, cardiac death, MI, all-cause death and ST. Patients with a SYNTAX score >32 were also more likely to have a peri-procedural complication. Multiple logistic regression analysis showed that the presence of PVD (P = 0.026, OR = 2.0), DM (P = 0.008, OR = 2.1), ACS presentation (P = 0.011, OR = 2.1) and SYNTAX score >=23 (P = 0.02, OR = 1.9) had a significant association with MACE. CONCLUSIONS: RA is safe and effective, with high rate of procedural success and relatively low incidence of MACE. PVD, DM, ACS presentation and SYNTAX score were significant predictors for MACE. (c) 2016 Wiley Periodicals, Inc. PMID- 27258653 TI - Adult-onset hyperthyroidism impairs spatial learning: possible involvement of mitogen-activated protein kinase signaling pathways. AB - Given evidence that mitogen-activated protein kinase (MAPK) activation is part of the nongenomic actions of thyroid hormones, we investigated the possible consequences of hyperthyroidism for the cognitive functioning of adult rats. Young adult rats were treated with L-thyroxine or saline. Twenty rats in each group were exposed to Morris water maze testing, measuring their performance in a hidden-platform spatial task. In a separate set of rats not exposed to Morris water maze testing (untrained rats), the expression and phosphorylated levels of p38-MAPK and of its two downstream effectors, Elk-1 and cAMP response element binding protein, were evaluated using quantitative reverse transcriptase-PCR and western blotting. Rats with hyperthyroidism showed delayed acquisition of learning compared with their wild-type counterparts, as shown by increased escape latencies and distance moved on the last two trials of daily training in the water maze. The hyperthyroid rats, however, showed no difference during probe trials. Western blot analyses of the hippocampus showed that hyperthyroidism increased phosphorylated p38-MAPK levels in untrained rats. Although our study is correlative in nature and does not exclude the contribution of other molecular targets, our findings suggest that the observed impairments in acquisition during actual learning in rats with hyperthyroidism may result from the increased phosphorylation of p38-MAPK. PMID- 27258652 TI - Compartmentation of metabolites in regulating epigenome of cancer. AB - Covalent modification of DNA and histones are important epigenetic events and the genome wide reshaping of epigenetic markers is common in cancer. The epigenetic markers are produced by enzymatic reactions and some of these reactions require the presence of metabolites as cofactors (termed Epigenetic Enzyme Required Metabolites, EERMs). Recent studies found that the abundance of these EERMs correlates with epigenetic enzyme activities. Also, the subcellular compartmentation, especially the nuclear localization of these EERMs may play a role in regulating the activities of epigenetic enzymes. Moreover, gene specific recruitment of enzymes which produce the EERMs in the proximity of the epigenetic modification events accompanying the gene expression regulation, were proposed. Therefore, it is of importance to summarize these findings of the EERMs in regulating the epigenetic modifications at both DNA and histone levels, and to understand how EERMs contribute to cancer development by addressing their global versus local distribution. PMID- 27258654 TI - Aberrant resting state in microRNA-30e rat model of cognitive impairment. AB - Increasing evidence suggests that microRNA (miRNA)-30e is implicated in the cognitive symptoms of many neuropsychiatric diseases. Our previous studies showed that miRNA-30e is associated with cognitive impairment in schizophrenia and depression. Neuroimaging studies have suggested that cognitive impairment is best characterized as abnormal local activity or a disconnection syndrome. Therefore, we constructed a cognitively impaired overexpressing miRNA-30e rat model for study using functional MRI (fMRI). The model was developed by transfected lentiviral particles carrying the miRNA-30e into the hippocampal dentate gyrus. The Morris water maze and open-field test were used to evaluate cognitive ability. We used the regional homogeneity approach to analyze resting-state fMRI data to explore the changes in regional synchronization. We then used Granger causality analysis to explore connectivity between the hippocampus, striatum, and thalamus. The model group showed higher regional homogeneity in the right hippocampus and striatum. One-way Granger causality connections were observed from the thalamus to the hippocampus in the model group, whereas connections from the thalamus to the striatum were observed in normal rats. After fluoxetine treatment, we found indirect connections between the thalamus and the striatum; we also found connections from the hippocampus to the striatum after Shuganjieyu capsule treatment. Our results support the hypothesis that cognitive impairment is related to disrupted local functionality or aberrant brain connectivity, with antidepressant drugs partially reversing cognitive impairment. The characteristics of resting-state fMRI in miRNA-30e overexpressing rats can provide further evidence for investigating the neural mechanisms of cognitive impairment in mental disorders. Video abstract; Supplemental digital content 1, http://links.lww.com/WNR/A385. PMID- 27258655 TI - Impact of the Type of First Medical Contact within a Guideline-Conform ST Elevation Myocardial Infarction Network: A Prospective Observational Registry Study. AB - AIMS: The impact of type of first medical contact (FMC) in the setting of a guideline conform metropolitan ST-elevation myocardial infarction (STEMI) network providing obligatory primary percutaneous coronary intervention (PCI) is unclear. METHODS AND RESULTS: 3,312 patients were prospectively included between 2006 and 2012 into a registry accompanying the "Cologne Infarction Model" STEMI network, with 68.4% primarily presenting to emergency medical service (EMS), 17.6% to non PCI-capable hospitals, and 14.0% to PCI-capable hospitals. Median contact-to balloon time differed significantly by FMC with 89 minutes (IQR 72-115) for EMS, 107 minutes (IQR 85-148) for non-PCI- and 65 minutes (IQR 48-91) for PCI-capable hospitals (p < 0.001). TIMI-flow grade III and in-hospital mortality were 75.7% and 10.4% in EMS, 70.3% and 8.6% in non-PCI capable hospital and 84.4% and 5.6% in PCI-capable hospital presenters, respectively (p both < 0.01). The association of FMC with in-hospital mortality was not significant after adjustment for baseline characteristics, but risk of TIMI-flow grade < III remained significantly increased in patients presenting to non-PCI capable hospitals. CONCLUSION: Despite differences in treatment delay by type of FMC in-hospital mortality did not differ significantly. The increased risk of TIMI-flow grade < III in patients presenting to non PCI-capable hospitals needs further study. PMID- 27258656 TI - A new science of happiness: the paradox of pleasure. AB - The pursuit of happiness is enshrined in the founding document of our nation as a fundamental and inalienable right. Yet nowhere is the method of this pursuit clearly defined. What, exactly, does it mean to be happy, and how can such happiness be sustained over the long term? Can happiness be accurately gauged or measured? How does the paradoxical relationship between happiness and pleasure shape our quest to lead the good life? And what does modern science have to tell us about this universal yet elusive pursuit? Steve Paulson, executive producer and host of To the Best of Our Knowledge, moderated a discussion that included attorney and author Kim Azzarelli, historian Darrin McMahon, and social psychologist Barry Schwartz, who joined forces to share their research and insight on happiness, pleasure, and the coveted good life. PMID- 27258657 TI - Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China. AB - Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ?10OH-PAHs determined in e-waste recycling area (GM: 25.4MUg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7MUg/g Cre) and urban (10.9MUg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6MUg/g Cre) showed significantly higher (p<0.01) urinary Sigma10OH-PAHs concentrations than non-occupationally exposed people (23.2MUg/g Cre) living in the e-waste recycling site. The differences in urinary Sigma10OH-PAHs levels between smokers (23.4MUg/g Cre) and non-smokers (24.7MUg/g Cre) were not significant (p>0.05) in e-waste dismantling sites, while these differences were significant (p<0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Sigma10OH PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1 hydroxypyrene (1-PYR) (r=0.284, p<0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies. PMID- 27258658 TI - Pregnancy and childhood exposure to residential traffic noise and overweight at 7years of age. AB - BACKGROUND: Exposure to road traffic noise has been associated with adiposity and diabetes in adults. The suggested pathways have been through sleep disturbance and stress. Children may be particularly susceptible to noise induced sleep disturbance and stress and the effects hereof. OBJECTIVES: To examine the association between traffic noise exposure during pregnancy and early childhood and adiposity in children. METHODS: We identified 40,974 singletons from the Danish National Birth Cohort with parentally given questionnaire information on weight and height at 7-years of age. Road and railway traffic noise were modeled at all historical addresses and expressed as time-weighted means for two exposure periods (pregnancy and childhood). Adiposity was assessed using BMI z-scores and a dichotomous measure of childhood overweight based on age and sex specific cut offs. Associations were analyzed using linear regression for BMI z-scores and logistic regression for risk of childhood overweight, adjusting for socioeconomic position, maternal BMI, maternal smoking, maternal age, parity and degree of urbanization. RESULTS: We found both pregnancy and childhood exposure to road traffic noise to be associated with a higher risk for childhood overweight (odds ratio (OR)=1.06 per 10dB, 95% confidence interval (CI): 1.00-1.12 for exposure during pregnancy and OR=1.06 per 10dB, 95% CI: 0.99-1.12 for childhood exposure). There were no associations between road traffic noise and BMI z-scores. We found no associations between railway noise and adiposity. CONCLUSIONS: We found suggestions of a positive association between road traffic noise and risk of overweight in 7-years old children. PMID- 27258659 TI - Associations of urinary metal levels with serum hormones, spermatozoa apoptosis and sperm DNA damage in a Chinese population. AB - BACKGROUND: Exposure to metals, including essential and nonessential elements, is widespread and may be associated with male reproductive health. OBJECTIVE: To examine whether environmental exposure to metals contributes to reproductive hormone changes, spermatozoa apoptosis and sperm DNA damage in a Chinese population. METHODS: Eighteen metals (aluminum, arsenic, antimony, chromium, cobalt, copper, cadmium, iron, lead, manganese, molybdenum, nickel, selenium, tin, tungsten, thallium, uranium and zinc) were analyzed in two urine samples collected a few hours apart from male partners of couples attending an infertility clinic. Multivariable linear regression models were used to assess the cross-sectional associations of average urinary metal levels with serum hormones (n=511), spermatozoa apoptosis measures (n=460) and sperm DNA damage parameters (n=516). RESULTS: We found significant inverse dose-dependent trends of urinary tin quartiles with total testosterone (T), and tin, nickel, zinc and molybdenum with the ratio of total T to luteinizing hormone (total T/LH ratio) (all Ptrend<0.05). Additionally, we found significantly dose-dependent trends of increasing urinary manganese quartiles with increasing percentage of Annexin V+/PI- spermatozoa and increasing iron with decreasing percentage of PI+ spermatozoa (both Ptrend<0.05). These dose-dependent trends remained suggestive or significant after controlling for multiple testing and other metals, and they persisted when the metals were modeled as continuous variables in a cubic spline analysis. There were no significant associations between urinary metals and sperm DNA damage after adjustment for multiple testing. CONCLUSION: Environmental exposure to tin, nickel, zinc and molybdenum may be associated decreased total T or total T/LH ratio; manganese may induce spermatozoa apoptosis, while iron may be important for living spermatozoa. However, additional prospective research is needed to corroborate these findings in the general population. PMID- 27258660 TI - Association of perfluoroalkyl substances exposure with reproductive hormone levels in adolescents: By sex status. AB - Polyfluoroalkyl substances (PFASs) are a group of common chemicals that ubiquitously exist in wildlife and humans. However, few studies have researched the effect of PFASs on reproductive hormones in adolescents. To provide information in this regard, we recruited 225 Taiwanese adolescents aged 13 15years from 2009 to 2010 to investigate the relationship between serum PFASs (PFOS, PFOA, PFBS, PFDA, PFDoA, PFHxA, PFHxS, PFNA and PFTA) and reproductive hormone concentrations using a cross-sectional study design. Results showed PFOS and PFTA levels were highest among the PFASs, with a median concentrations of 29.9 (interquartile range: 13.0-43.8) ng/mL and 6.0 (0.6-25.9) ng/mL in males, and a median concentrations of 28.8 (14.8-42.6) ng/mL and 4.5 (0.3-18.4) ng/mL in females. After adjustment for confounding factors, nonsignificant associations between PFASs and reproductive hormone were found except for PFNA with ln(estradiol) (beta=0.2060, 95%CI: 0.0016, 0.4105). When stratified by sex, more significant associations were found in males than in females. Among males, PFASs were negatively associated with ln(testosterone) level for PFOS (beta=-0.0029, 95%CI: -0.0055, -0.0003), PFDA (beta=-0.2565, 95%CI: -0.4135, -0.0994), PFHxA (beta=-0.3095, 95%CI: -0.5942, -0.0248), and PFNA (beta=-0.4233, 95%CI: -0.6998, 0.1467). Furthermore, male participant ln(estradiol) levels were positively associated with PFOA (beta=0.0921, 95%CI: 0.0186, 0.1656), and PFHxS (beta=0.0462, 95%CI: 0.0020, 0.0905). Among females, a significant relationship was found only for PFDoA with ln(testosterone) (beta=-0.0119, 95%CI: -0.0227, 0.0010). In conclusion, this study showed higher levels of PFASs coincide with lower testosterone and higher estradiol levels, and more significant associations of PFASs with reproductive hormone were found in males than in females. PMID- 27258661 TI - Children's well-being at schools: Impact of climatic conditions and air pollution. AB - Human civilization is currently facing two particular challenges: population growth with a strong trend towards urbanization and climate change. The latter is now no longer seriously questioned. The primary concern is to limit anthropogenic climate change and to adapt our societies to its effects. Schools are a key part of the structure of our societies. If future generations are to take control of the manifold global problems, we have to offer our children the best possible infrastructure for their education: not only in terms of the didactic concepts, but also with regard to the climatic conditions in the school environment. Between the ages of 6 and 19, children spend up to 8h a day in classrooms. The conditions are, however, often inacceptable and regardless of the geographic situation, all the current studies report similar problems: classrooms being too small for the high number of school children, poor ventilation concepts, considerable outdoor air pollution and strong sources of indoor air pollution. There have been discussions about a beneficial and healthy air quality in classrooms for many years now and in recent years extensive studies have been carried out worldwide. The problems have been clearly outlined on a scientific level and there are prudent and feasible concepts to improve the situation. The growing number of publications also highlights the importance of this subject. High carbon dioxide concentrations in classrooms, which indicate poor ventilation conditions, and the increasing particle matter in urban outdoor air have, in particular, been identified as primary causes of poor indoor air quality in schools. Despite this, the conditions in most schools continue to be in need of improvement. There are many reasons for this. In some cases, the local administrative bodies do not have the budgets required to address such concerns, in other cases regulations and laws stand in contradiction to the demands for better indoor air quality, and sometimes the problems are simply ignored. This review summarizes the current results and knowledge gained from the scientific literature on air quality in classrooms. Possible scenarios for the future are discussed and guideline values proposed which can serve to help authorities, government organizations and commissions improve the situation on a global level. PMID- 27258662 TI - A comparison of the effects of a 4% modified fluid gelatin and a 6% hydroxyethyl starch on haemodilution, colloid osmotic pressure, haemostasis and renal parameters in healthy ponies. AB - REASONS FOR PERFORMING STUDY: Adverse effects on renal health and haemostasis have been documented in human patients administered hydroxyethyl starches (HESs). Gelatins may represent useful substitutes should similar adverse effects be identified in horses. OBJECTIVES: To compare the effects of a 4% modified fluid gelatin (MFG) with a 6% (130/0.4) HES on haemodilution, colloid osmotic pressure (COP), haemostasis and renal parameters in healthy ponies. STUDY DESIGN: Randomised crossover experiment. METHODS: Three treatments (Treatment A: 10 ml/kg bwt HES; Treatment B: 10 ml/kg bwt MFG; Treatment C: 20 ml/kg bwt MFG) were administered to 6 healthy ponies with a 1 week washout period between treatments. Haematocrit, platelet count, total serum protein, COP, thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen concentration were measured at baseline and at multiple time points up to 24 h post-infusion. Serum creatinine concentration, urine specific gravity (USG), urine protein:creatinine ratio (UPC), urine gamma glutamyltransferase:creatinine ratio (UGC) and urine sediment examination (USE) were performed before and at 24 h after each treatment, as well as at 1 week after the final treatment. RESULTS: All treatments resulted in significant haemodilution and increases in COP. Treatment C had a significantly greater effect on haematocrit than the other treatments. The platelet count decreased with all treatments and was significantly lower following Treatment C compared with Treatment B. No clinically relevant differences were observed in any of the TEG parameters within or between treatments. No significant differences in PT, aPTT or fibrinogen concentration were observed among treatments. Serum creatinine concentration, UPC and UGC did not change significantly between pre- and post study measurements. USG and USE remained within normal limits. CONCLUSIONS: Modified fluid gelatin could be considered as an alternative to HES for volume expansion and oncotic support. Neither MFG nor HES were associated with clinically significant adverse effects on haemostasis or renal parameters. PMID- 27258663 TI - Postoperative complications in cardiac patients undergoing noncardiac surgery. AB - PURPOSE OF REVIEW: In this article we review the current knowledge on the underlying mechanisms of perioperative myocardial injury, the preoperative methods of predicting these complications, the diagnostic tools for detecting perioperative myocardial injuries, and the available protective strategies to prevent or attenuate the extent of myocardial injury. RECENT FINDINGS: The last years' new insights have provided a better understanding of the problem of perioperative myocardial injury and infarction. Specifically, the importance of early diagnosis and prompt treatment are increasingly getting attention. Concomitantly, the results of recent large multicenter studies have challenged classical therapeutic approaches in the perioperative treatment of cardiac patients undergoing noncardiac surgery. SUMMARY: These new insights will help to better tailor individual strategies to prevent or minimize perioperative cardiac complications. Especially, early diagnosis and intensification of treatment will get specific interest in the coming years. PMID- 27258664 TI - Update on perioperative acute kidney injury. AB - PURPOSE OF REVIEW: In this review, we discuss the latest updates on perioperative acute kidney injury (AKI) and the specific considerations that are relevant to different surgeries and patient populations. RECENT FINDINGS: AKI diagnosis is constantly evolving. New biomarkers detect AKI early and shed a light on the possible cause of AKI. Hypotension, even for a short duration, is associated with perioperative AKI. The debate on the deleterious effects of chloride-rich solutions is still far from conclusion. Remote ischemic preconditioning is showing promising results in the possible prevention of perioperative AKI. No definite data show a beneficiary effect of statins, fenoldepam, or sodium bicarbonate in preventing AKI. SUMMARY: Perioperative AKI is prevalent and associated with significant morbidity and mortality. Considering the lack of effective preventive or therapeutic interventions, this review focuses on perioperative AKI: measures for early diagnosis, defining risks and possible mechanisms, and summarizing current knowledge for intraoperative fluid and hemodynamic management to reduce risk of AKI. PMID- 27258665 TI - Protein delivery in critical illness. AB - PURPOSE OF REVIEW: Protein delivery in the critically ill still is a highly debated issue. Here, we discuss only the most recent updates in the literature concerning protein nutrition of the critically ill. RECENT FINDINGS: Up to now, there are no randomized controlled trials (RCTs) published on enteral provision of protein that were randomized for protein level of intake. In the past year, there have been two new observational studies published, one of which in critically ill children. Also, two randomized controlled trials with high parenteral amino acid provision have been published. The overall view on nutrition support has not been changed convincingly by these studies. Recent findings have confirmed that protein and amino acid provision are highly important for outcome in critically ill patients. For the first time, a randomized study confirmed this, however, only on the short term. The other RCT confirmed that an extreme dosing of amino acids is not related to improvement in outcome. One observational study showed that the effect of protein on outcome should be adjusted for energy intake and vice versa, showing that adequate protein is related to improved outcome and adequate energy provision is not. The other observational study confirmed importance of protein in paediatric ICU but also gained some insight into improvement of protein delivery by postpyloric feeding and usefulness of a dedicated dietitian in the ICU. SUMMARY: We will continue to improve protein delivery to critically ill patients; however, the quest for evidence and feeding guidelines still remains. PMID- 27258666 TI - Bedside nutrition evaluation and physical assessment techniques in critical illness. AB - PURPOSE OF REVIEW: The purpose of this review is to highlight emerging techniques used to determine body composition early in ICU stay, their prediction of poor outcome, and what is required before they can be more widely used. RECENT FINDINGS: Opportunistic use of imaging techniques to assess muscle mass shows promise with regard to predicting patient outcomes; however, some of these techniques are expensive. Mid-arm muscle circumference and physical assessments of muscle wasting and subcutaneous fat loss using the subjective global assessment (SGA) are simple cheap tools that can be undertaken at the ICU patient bedside. Furthermore, each of these simple measures is a better predictor of patient outcome than BMI. SUMMARY: Mid-arm muscle circumference, SGA fat loss, and SGA muscle wasting have each been found to be better predictors of poor outcome than BMI in ICU patients.Mid-arm muscle circumference, SGA fat loss, and SGA muscle wasting may be able to identify patients who are most likely to benefit from enhanced nutrition support.We need further research incorporating the use of these simple measures to evaluate their ability to accurately identify patients most likely to benefit from enhanced nutritional support. PMID- 27258667 TI - An Easy Access to Organic Salt-Based Stimuli-Responsive and Multifunctional Supramolecular Hydrogels. AB - By exploiting orthogonal hydrogen bonding involving supramolecular synthons and hydrophobic/hydrophilic interactions, a new series of simple organic salt based hydrogelators derived from pyrene butyric acid and its beta-alanine amide derivative, and various primary amines has been achieved. The hydrogels were characterised by microscopy, table-top rheology and dynamic rheology. FTIR, variable-temperature (1) H NMR and emission spectroscopy established the role of various supramolecular interactions such as hydrogen bonding and pi-pi stacking in hydrogelation. Single-crystal X-ray diffraction (SXRD) studies supported the conclusion that orthogonal hydrogen bonding involving amide-amide and primary ammonium monocarboxylate (PAM) synthons indeed played a crucial role in hydrogelation. The hydrogels were found to be stimuli-responsive and were capable of sensing ammonia and adsorbing water-soluble dye (methylene blue). All the hydrogelators were biocompatible (MTT assay in RAW 264.7 cells), indicating their suitability for use in drug delivery. PMID- 27258668 TI - HYPERREFLECTIVE FOCI AS AN INDEPENDENT VISUAL OUTCOME PREDICTOR IN MACULAR EDEMA DUE TO RETINAL VASCULAR DISEASES TREATED WITH INTRAVITREAL DEXAMETHASONE OR RANIBIZUMAB. AB - PURPOSE: To evaluate the potential role of hyperreflective foci (HF) in predicting visual outcome in patients undergoing treatment for macular edema due to retinal vascular diseases. METHODS: Data and images of 92 patients with macular edema due to diabetes mellitus or branch retinal vein occlusion, treated with either intravitreal dexamethasone implant or ranibizumab, were analyzed. All patients underwent best-corrected visual acuity measurement, slit-lamp examination, spectral domain optical coherence tomography at baseline and at all time points of the follow-up (Month 1, 2, 3, 6, and 9). Generalized least squares random effects linear or logistic regression analysis was used to investigate potential factors associated with the final best-corrected visual acuity and number of HF, respectively. RESULTS: Increasing age (P < 0.001), central retinal thickness (P < 0.001), number of HF (P = 0.028), presence of subretinal fluid (P < 0.001), intraretinal fluid (P < 0.001), intraretinal cysts (P < 0.001), and disruption of ellipsoid zone/external limiting membrane (P < 0.001) were significantly associated with poorer visual outcome. Factors associated with HF were increasing central retinal thickness (P = 0.003), presence of subretinal fluid (P = 0.049), intraretinal fluid (P = 0.002), cysts (P = 0.015), and disruption of ellipsoid zone (P = 0.047). No significant differences in change in best-corrected visual acuity, central retinal thickness, and HF were observed between the two treatment groups. CONCLUSION: Hyperreflective foci are associated with poorer visual outcome in patients with macular edema due to retinal vascular diseases. Similar reductions in HF are achieved by intravitreal steroid and anti vascular endothelial growth factor agent. PMID- 27258669 TI - ANGIOGRAPHIC FINDINGS OF RANIBIZUMAB-RESISTANT POLYPOIDAL CHOROIDAL VASCULOPATHY AFTER SWITCHING TO A TREAT-AND-EXTEND REGIMEN WITH INTRAVITREAL AFLIBERCEPT. AB - PURPOSE: The aim of this study was to study the angiopathic findings of ranibizumab-resistant polypoidal choroidal vasculopathy after switching to a treat-and-extend regimen with intravitreal aflibercept. METHODS: The authors retrospectively reviewed 17 eyes of 17 Japanese patients with polypoidal choroidal vasculopathy (10 men and 7 women, age: 73.8 +/- 7.4 years) who were treated with intravitreal aflibercept (2 mg/0.05 mL) injections from February 2013 to August 2014 at Tokyo University Hospital. All patients had switched to aflibercept because their polypoidal choroidal vasculopathy had been refractory to ranibizumab. RESULTS: The mean logMAR best-corrected visual acuity at baseline and after 12 months of therapy was 0.30 +/- 0.29 (Snellen equivalent: 20/40) and 0.17 +/- 0.26 (20/30) (paired t-test P < 0.001). Visual acuity remained stable in 5 cases (29%), deteriorated in 3 (18%), and improved in 9 (53%). Branching vascular networks persisted in all 17 eyes but shrank in 15 (88%). The mean lesion diameter was 3329 +/- 1261 MUm at baseline and 3180 +/- 1247 MUm after 12 months (P = 0.0002). CONCLUSION: A treat-and-extend regimen with intravitreal aflibercept for ranibizumab-resistant patients resulted in branching vascular network shrinkage over a 1-year period. PMID- 27258670 TI - PREVALENCE AND ASSOCIATIONS OF MYELINATED RETINAL NERVE FIBERS: Results From the Population-Based Gutenberg Health Study. AB - PURPOSE: To determine the prevalence, ocular, and systemic associations of myelinated retinal nerve fibers (MRNF) in a Caucasian cohort. METHODS: The Gutenberg Health Study (GHS) is a population-based, prospective cohort study encompassing 15,010 subjects in Germany. Gutenberg Health Study participants, aged 35 to 74 years, stratified for gender, decades of age, and residence were examined for ophthalmologic and systemic conditions. Optic disc centered and macular photographs were reviewed for the presence of MRNF. RESULTS: In 25,728 eyes of 12,906 participants (86.0% of the cohort), the prevalence of MRNF was 0.4%. In a binary logistic regression analysis, MRNF was positively associated with history of stroke (OR, 6.8; 95% CI, 2.9-16.1; P < 0.001). Myelinated retinal nerve fibers was not associated with age, sex, cardiovascular conditions other than stroke or ocular parameters, such as refraction, visual acuity, intraocular pressure, or central corneal thickness. CONCLUSION: This population-based study provides novel data on the prevalence of MRNF in Western Europe. We report a positive association between history of stroke and MRNF. It adds an additional retinal sign for stroke and calls for further studying of the behavior of oligodendrocytes within cerebrovascular diseases. PMID- 27258671 TI - LONG-TERM OUTCOMES OF INTRAVITREAL BEVACIZUMAB THERAPY FOR SUBRETINAL NEOVASCULARIZATION SECONDARY TO IDIOPATHIC MACULAR TELANGIECTASIA TYPE 2. AB - PURPOSE: To assess the long-term visual acuity results for intravitreal bevacizumab therapy in the treatment of subretinal neovascular membrane (SRNVM) secondary to idiopathic macular telangiectasia (Mactel) Type 2. METHODS: This retrospective review of a consecutive, interventional case series includes patients with SRNVM secondary to Mactel Type 2 who were seen at Cincinnati Eye Institute from February 2006 to December 2014. Best-corrected visual acuity, fluorescein angiography, and optical coherence tomography measurements were performed. Exclusion criteria were the following: Mactel Type 2 patients without SRNVM, Mactel Type 1 patients, patients who had SRNVM or macular edema related to other maculopathies, and patients who had pars plana vitrectomy or laser treatment to the macula during the course of care or before their first visit. RESULTS: Twenty-five eyes of 20 patients with SRNVM secondary to Mactel Type 2 were included in the study. The mean baseline best-corrected visual acuity was 20/91 (median: 20/69) and the mean final best-corrected visual acuity was 20/62 (median: 20/60) at the last visit (P < 0.0001). The mean number of injections was 8.4 +/- 11.1 (range: 2-53, median: 4). The mean pretreatment central macular thickness of 254 MUm improved to 205 MUm at the final visit (P = 0.011). No complications related to intravitreal bevacizumab injection were noted during the mean follow-up time of 40.8 +/- 33.7 months (range: 4-108 months, median: 24 months). CONCLUSION: Intravitreal bevacizumab therapy is an effective long-term treatment modality for SRNVM secondary to Mactel Type 2 based on improvement in best-corrected visual acuity and associated reduction in central macular thickness. PMID- 27258672 TI - VOLUMETRIC SINGLE-LAYER INNER RETINAL ANALYSIS IN PATIENTS WITH HYDROXYCHLOROQUINE TOXICITY. AB - PURPOSE: To compare retinal layer volumes using spectral-domain optical coherence tomography between eyes with hydroxychloroquine (HCQ) toxicity and control eyes. METHODS: Using a previously validated algorithm, volumetric analysis from the macular cube scan of the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina (outer plexiform layer to retinal pigment epithelium) layers were compared in three sets of patients: patients with a clinical diagnosis of HCQ toxicity, age-matched patients taking HCQ but not manifesting overt toxicity, and age-matched control patients. RESULTS: There were 14 patients in each group. The ganglion cell layer (P = 0.01), inner plexiform layer (P = 0.004), inner nuclear layer (P < 0.001), and outer plexiform layer to retinal pigment epithelium (P < 0.001) volumes were significantly reduced in HCQ toxicity eyes relative to the HCQ exposure eyes. There were no significant inner and outer retinal volume differences between the HCQ exposure group and group with no HCQ use (P > 0.05 for all layers). Increasing disease severity correlated with increasing volume loss in the inner retina (2.27 mm in early disease vs. 1.78 mm in advanced retinopathy, P = 0.02). CONCLUSION: Hydroxychloroquine toxicity seems to result in both outer and inner retinal volumetric thinning compared with age-matched control patients and patients taking HCQ but not manifesting toxicity. PMID- 27258673 TI - Synthesis of 6-phosphofructose aspartic acid and some related Amadori compounds. AB - We describe the synthesis and characterization of 6-phosphofructose-aspartic acid, an intermediate in the metabolism of fructose-asparagine by Salmonella. We also report improved syntheses of fructose-asparagine itself and of fructose aspartic acid. PMID- 27258674 TI - Helical Foldamers Incorporating Photoswitchable Residues for Light-Mediated Modulation of Conformational Preference. AB - An E unsaturated fumaramide linkage may be introduced into Aib peptide foldamer structures by standard coupling methods and photoisomerized to its Z (maleamide) isomer by irradiation with UV light. As a result of the photoisomerization, a new hydrogen-bonded contact becomes possible between the peptide domains located on either side of the unsaturated linkage. Using the fumaramide/maleamide linker to couple a chiral and an achiral fragment allows the change in hydrogen bond network to communicate a conformational preference, inducing a screw sense preference in the achiral domain of the maleamide-linked foldamers that is absent from the fumaramides. Evidence for the induced screw sense preference is provided by NMR and CD, and also by the turning on by light of the diastereoselectivity of a peptide chain extension reaction. The fumaramide/maleamide linker thus acts as a "conformational photodiode" that conducts stereochemical information as a result of irradiation by UV light. PMID- 27258675 TI - Synthesis of Free-Base 10-Azacorroles. AB - A novel synthetic protocol has been developed for free-base 10-azacorroles. Ni(0) mediated homocoupling of nitrogen-bridged bisdipyrrin Zn(II) complexes afforded a series of free-base 5,15-diaryl-10-azacorroles in good yields. Pd(II) and Cu(II) complexes have been prepared through metalation of free-base 10-azacorroles. Optical and electrochemical properties of 10-azacorrole metal complexes can be tuned by meso-aryl substituents and central metals. Cyclic voltammetry and theoretical calculations elucidated that the central metals of 10-azacorroles significantly affected their electronic properties. PMID- 27258676 TI - Primary Retroperitoneal Mucinous Cystic Neoplasm: Authors' Experience and Review of the Literature. AB - INTRODUCTION: Primary retroperitoneal mucinous cystic neoplasm (PRMCN) is a rare retroperitoneal tumor with female predilection. It is classified into 3 types: benign mucinous cystadenoma (MCA), borderline mucinous cystadenoma (MCAb), malignant mucinous cystadenocarcinoma (MCAc). This study retrospectively evaluates the prevalence of PRMCN among retroperitoneal neoplasms resected between June 2006 and January 2015 at a referral center. Authors' experience with PRMCN is reviewed, and a new case of PRMCN, incidentally diagnosed during pregnancy is reported. A literature review using PubMed is also presented, discussing several issues concerning clinicopathologic features, treatment options, and long-term outcome of PRMCN. CASE REPORT: A 36-year-old woman was incidentally diagnosed with a 12-cm retroperitoneal cyst discovered by ultrasound at 36 weeks of gestation. Eight months later the patient was referred to the department of surgery, the Tel Aviv Sourasky Medical Center. By that time, the patient has sensed local discomfort. Physical examination revealed a right abdomen mass with mild tenderness. Computed tomographic scan depicted the cyst, located along the right paracolic gutter, displacing the right colon medially. The patient underwent complete laparoscopic resection of a 15-cm cyst, without its disruption. The cyst was drained inside an endobag and retrieved. The patient was discharged home on postoperative day 1. The pathology was MCA. Long-term result was no evidence of disease for 9 months. DISCUSSION: The prevalence of PRMCN among resected retroperitoneal neoplasms was 1.95% (3/154 neoplasms). The treatment of choice is complete tumor resection. Surgical technique should be chosen depending on the surgeon's expertise and tumor factors affecting safe resection. Surgery timing during pregnancy should be dictated by both risk of malignancy and obstetric considerations. As for malignant PRMCN, radical surgery does not seem justified, especially in reproductive females. Adjuvant chemotherapy should probably be reserved for metastatic disease, recurrence, and tumor rupture. Long-term follow-up is lacking, although it is important to better define the prognosis of PRMCN. PMID- 27258677 TI - Survival of Patients With Multiple Intracranial Metastases Treated With Stereotactic Radiosurgery: Does the Number of Tumors Matter? AB - BACKGROUND: Defining prognostic factors is a crucial initial step for determining the management of patients with brain metastases. Randomized trials assessing radiosurgery have commonly limited inclusion criteria to 1 to 4 brain metastases, in part due to multiple retrospective studies reporting on the number of brain metastases as a prognostic indicator. The present study reports on the survival of patients with 1 to 4 versus >=5 brain metastases treated with radiosurgery. METHODS: We evaluated a retrospective multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or Cyberknife) between 2001 and 2014. A total of 243 patients were included in the analysis. Patients with 1 to 4 brain metastases were compared with patients with >=5 brain metastases using a standard statistical analysis. Cox hazard regression was used to construct a multivariable model of overall survival (OS). To find covariates that best separate the data at each split, a machine learning technique Chi-squared Automated Interaction Detection tree was utilized. RESULTS: On Pearson correlation, systemic disease status, number of intracranial metastases, and overall burden of disease (number of major involved organ systems) were found to be highly correlated (P<0.001). Patients with 1 to 4 metastases had a median OS of 10.8 months (95% confidence interval, 6.1-15.6 mo), compared with a median OS of 8.5 months (95% confidence interval, 4.4-12.6 mo) for patients with >=5 metastases (P=0.143). The actuarial 6 month local failure rate was 5% for patients with 1 to 4 metastases versus 3.2% for patients with >=5 metastases (P=0.404). There was a significant difference in systemic disease status between the 2 groups; 30% of patients had controlled systemic disease in the <5 lesions group, versus 8% controlled systemic disease in the >=5 lesions group (P=0.005). Patients with 1 to 4 metastases did not have significantly improved OS in a multivariable model adjusting for systemic disease status, systemic extracranial metastases, and other key variables. The Chi-squared Automated Interaction Detection tree (machine learning technique) algorithm consistently identified performance status and systemic disease status as key to disease classification, but not intracranial metastases. CONCLUSIONS: Although the number of brain metastases has previously been accepted as an independent prognostic indicator, our multicenter analysis demonstrates that the number of intracranial metastases is highly correlated with overall disease burden and clinical status. Proper matching and controlling for these other determinants of survival demonstrates that the number of intracranial metastases alone is not an independent predictive factor, but rather a surrogate for other clinical factors. PMID- 27258678 TI - Locally Advanced Cervical Cancer: Outcomes With Variable Adherence to Treatment. AB - OBJECTIVE: Adherence to treatment regimen and schedule is recommended to improve control of disease and overall survival (OS) in locally advanced cervical cancer. However, treatment-related toxicities and patient and physician factors all impact timely completion of treatment. We sought to correlate adherence to treatment plan with survival and toxicities of patients treated for locally advanced cervical cancer. MATERIALS AND METHODS: A retrospective review of patients treated for advanced cervical cancer at our institution between 2003 and 2011 was performed. Demographics, clinicopathologic variables, treatment, and disease outcomes were collected. Endpoints of disease outcome were disease-free survival and OS. Statistical analyses were performed using the Kaplan-Meier method, log-rank test, and Cox regression analysis. RESULTS: A total of 162 patients met the inclusion criteria and were included in study analysis. A total of 95% of patients were treated with both radiation and concurrent chemotherapy. Mean radiation dose to point A was 72 Gy. In total, 77% had complete response to primary therapy. Severe (grade 3/4) late radiation toxicities were seen in 10.5% of patients. Stage and total radiation dose to point A were significant predictors of survival for the entire cohort. Among patients receiving at least 72 Gy and brachytherapy, duration of treatment was significantly associated with both disease-free survival and OS. CONCLUSIONS: Adherence to both optimal treatment time and radiation dose is significantly associated with improved survival. Total radiation dose is an independent predictor of survival among patients with locally advanced cervical cancer. PMID- 27258679 TI - Noble-Metal Nanocrystals with Controlled Facets for Electrocatalysis. AB - Noble-metal nanocrystals (NCs) show excellent catalytic performance for many important electrocatalysis reactions. The crystallographic properties of the facets by which the NCs are bound, closely associated with the shape of the NCs, have a profound influence on the electrocatalytic function of the NCs. To develop an efficient strategy for the synthesis of NCs with controlled facets as well as compositions, understanding of the growth mechanism of the NCs and their interaction with the chemical species involved in NC synthesis is quite important. Furthermore, understanding the facet-dependent catalytic properties of noble-metal NCs and the corresponding mechanisms for various electrocatalysis reactions will allow for the rational design of robust electrocatalysts. In this review, we summarize recently developed synthesis strategies for the preparation of mono- and bimetallic noble-metal NCs by classifying them by the type of facets through which they are enclosed and discuss the electrocatalytic applications of noble-metal NCs with controlled facets, especially for reactions associated with fuel-cell applications, such as the oxygen reduction reaction and fuel (methanol, ethanol, and formic acid) oxidation reactions. PMID- 27258680 TI - Porous Coordination Polymers Based on {Mn6} Single-Molecule Magnets. AB - In this paper, three isostructural porous coordination polymers, namely, [Mn6(MU3 O)2(sao)6(DMF)4(L(1))2/3].4DMF.2H2O.2CH3OH (1), [Mn6(MU3 O)2(sao)6(DMF)4(L(2))2/3].4DMF.2H2O.2CH3OH (2), and [Mn6(MU3 O)2(sao)6(DMF)4(L(3))2/3].4DMF.4H2O.2CH3OH (3) (DMF = dimethylformamide, H2sao = salicylaldoxime, H3L(1) = benzene-1,3,5-trisbenzoic acid, H3L(2) = 4,4',4"-s triazine-2,4,6-triyltribenzoic acid, and H3L(3) = 2,4,6-tris(4-carboxyphenoxy) 1,3,5-s-triazine), based on the oximato-bridged {Mn6} single-molecule magnet (SMM) and tricarboxylic acid ligands, were designed and synthesized. X-ray structural analysis shows that they possess a two-dimensional layered structure, where the {Mn6} moieties are linked by the corresponding (L(x))(3-) carboxylate ligands (x = 1, 2, 3) forming a huge honeycomb layer. These compounds not only show the SMM behavior as confirmed by alternative current susceptibility measurements but also show selectivity for CO2 over N2 at 273 K. On the basis of the magnetic fitting to the magnetic susceptibilities and the field dependence of magnetization for complexes 1-3, the spin ground states are S = 4. Compared with isolated {Mn6} SMMs with S = 4, the out-of-phase susceptibilities of 1-3 show obvious peaks only under the external direct-current field of 2 kOe. However, no peaks in chim" are observed in the partially desolvated sample of compound 1. PMID- 27258681 TI - Stakeholder Participation in System Change: A New Conceptual Model. AB - BACKGROUND: A recent change in Canada's primary care system led to the introduction of Nurse Practitioner-Led clinics. The literature suggests that stakeholders can influence system change initiatives. However, very little is known about healthcare stakeholder motivations, particularly stakeholders who are seen as resistors to change. AIM: To examine stakeholder participation in the system change process that led to the introduction of the first Nurse Practitioner-Led clinic in Ontario. METHODS: This single case study included two site visits, semistructured individual tape-recorded interviews, and the examination of relevant public documents. Qualitative content analysis was used to analyze the data. RESULTS: Sixteen individuals from different healthcare sectors and professions participated in the interviews and 20 documents were reviewed. Six key themes emerged from the data. Linking Evidence to Action The findings from the study present a new perspective on stakeholder participation that includes both those who supported the proposed change and those who advocated for a different change. The findings identify stakeholder activities used to shape, share, and protect their visions for system change. The conceptual model presented in this study adds to the understanding of challenges and complexities involved in healthcare system change. Understanding why and how stakeholders participate in change can help healthcare leaders in planning activities to enhance stakeholder involvement in healthcare system change. PMID- 27258682 TI - Sliced Magnetic Polyacrylamide Hydrogel with Cell-Adhesive Microarray Interface: A Novel Multicellular Spheroid Culturing Platform. AB - Cell-adhesive properties are of great significance to materials serving as extracellular matrix mimics. Appropriate cell-adhesive property of material interface can balance the cell-matrix interaction and cell-cell interaction and can promote cells to form 3D structures. Herein, a novel magnetic polyacrylamide (PAM) hydrogel fabricated via combining magnetostatic field induced magnetic nanoparticles assembly and hydrogel gelation was applied as a multicellular spheroids culturing platform. When cultured on the cell-adhesive microarray interface of sliced magnetic hydrogel, normal and tumor cells from different cell lines could rapidly form multicellular spheroids spontaneously. Furthermore, cells which could only form loose cell aggregates in a classic 3D cell culture model (such as hanging drop system) were able to be promoted to form multicellular spheroids on this platform. In the light of its simplicity in fabricating as well as its effectiveness in promoting formation of multicellular spheroids which was considered as a prevailing tool in the study of the microenvironmental regulation of tumor cell physiology and therapeutic problems, this composite material holds promise in anticancer drugs or hyperthermia therapy evaluation in vitro in the future. PMID- 27258683 TI - Hb Dapu (HBA2: c.52G > T): A Novel Nondeletional alpha-Thalassemia Mutation. AB - We report a novel mutation on the alpha2-globin gene, Hb Dapu [alpha17(A15)Val >Phe (alpha2); HBA2: c.52G > T] detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by electrophoretic or chromatographic methods. The combination of this mutation with an in cis deletion of a double alpha-globin gene resulting in a mild form of Hb H (beta4) disease, is consistent with a thalassemic phenotype associated with the novel mutation. PMID- 27258684 TI - Cachexia in children with chronic kidney disease: challenges in diagnosis and treatment. AB - PURPOSE OF REVIEW: Although cachexia is highly prevalent in adult patients with chronic kidney disease (CKD), it is understudied and less well characterized in children. Recent evidence suggests that cachexia is also prevalent in children with CKD but presents challenges in diagnosis and treatment. RECENT FINDINGS: A study from the CKD in children cohort showed that CKD cachexia or protein-energy wasting, using modified pediatric diagnostic criteria, such as lack of expected weight gain instead of weight loss and BMI for height age, had a prevalence of 7 20%. When growth indices such as height SD score (SDS)/height velocity SDS was included in the criteria, cachexia or PEW correlated with the morbidity outcome of increased hospitalization risk in children with CKD. Conversely, aggressive nutritional supplementation in children with advanced CKD, with nasogastric or gastric tube feeding, led to prevalence of obesity over that of cachexia. Body habitus of underweight and obesity have been shown to be associated with the worst clinical outcomes in both adults and children with CKD. SUMMARY: Optimal nutritional therapy remains the mainstay of treatment of cachexia in CKD children with therapeutic goals of maintaining BMI as well as linear growth within the normal range. PMID- 27258685 TI - Efficiency improvement of new Tetrathienoacene-based dyes by enhancing donor, acceptor and bridge units, a theoretical study. AB - A series of metal free Tetrathienoacene-based (TTA-based) organic dyes are designed and investigated as sensitizers for application in dye sensitized solar cells (DSSCs). Density function theory and time dependent density function theory calculations were performed on these dyes at vacuum and orthodichlorobenzene as the solvent. Effects of changing pi-conjugation bridges and different functional groups in acceptor and donor units were investigated. UV-Vis absorption spectra were simulated to show the wavelength shifting and absorption properties. Inserting nitro and acyl chloride functional groups in acceptor and NH2 in donor units leads to the reduction of HOMO-LUMO gap by lowering the lowest unoccupied molecular orbital (LUMO) energy level and raising the highest occupied molecular orbital (HOMO) energy level and the increase in effective parameters in DSSC' efficiency. The results show that changing spacer units from thiophene to furan has a great effect on electronic structure and absorption spectra. Investigation of the electron distributions of frontier orbitals shows the HOMO and LUMO localization in donor and acceptor, respectively. Some key parameters that were studied here include light harvesting efficiency, free energy of electron injection and open circuit photo-voltage. PMID- 27258686 TI - A novel tripodal colorimetric and fluorescence "turn on" chemosensor for AcO(-) and F(-) anions in CH3CN. AB - A novel chemosensor, 3',3''',3'''"-(((nitrilotris(ethane-2,1 diyl))tris(azanylylidene))tris(methanylylidene))tris(4-hydroxy-4' biphenylcarbonitrile) (L) was synthesized and characterized by the combination of (1)H,(13)C, APT, COSY NMR, FT-IR, and elemental analysis. The behavior of the receptor (L) toward different anions was investigated using UV-visible and fluorescence spectroscopy. The receptor (L) indicated an efficient colorimetric "naked-eye" and "turn on" fluorescent response for fluoride and acetate in CH3CN, respectively. PMID- 27258687 TI - Comparison of collision-induced dissociation and electron-induced dissociation of phillyrin using FT-ICR MS. AB - Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry using collision-induced dissociation (CID) and electron capture dissociation (ECD) at high mass resolution was first applied to investigate the characteristic fragment ions of phillyrin. The CID experimental results demonstrated the elemental composition of fragment ions unambiguously, so a reasonable fragmentation pathway of phillyrin was proposed. The ECD fragmentation mechanism was believed to be fundamentally different from the CID method. ECD could be used not only in the biological field but also as a powerful complement to the structural identification of small molecular compounds. The characteristic fragmentation pathways were helpful in analyzing and interpreting the stability and property of the parent ion. PMID- 27258688 TI - Pseudo-Ligandless Click Chemistry for Oligonucleotide Conjugation. AB - Particularly for its use in bioconjugations, the copper-catalyzed (or copper promoted) azide-alkyne cycloaddition (CuAAC) reaction or 'click chemistry', has become an essential component of the modern chemical biologist's toolbox. Click chemistry has been applied to DNA, and more recently, RNA conjugations, and the protocols presented here can be used for either. The reaction can be carried out in aqueous buffer, and uses acetonitrile as a minor co-solvent that serves as a ligand to stabilize the copper. The method also includes details on the analysis of the reaction product. (c) 2016 by John Wiley & Sons, Inc. PMID- 27258689 TI - Liquid Exfoliation of Layered Transition Metal Dichalcogenides for Biological Applications. AB - Known to possess distinctive properties that differ greatly from their bulk form, layered two-dimensional materials have been extensively studied and incorporated into many versatile applications ranging from optoelectronics to sensors. For biomedical research, two-dimensional transition metal dichalcogenides (2D TMDs) have garnered much interest as they have been shown to exhibit relatively low toxicity, high stability in aqueous environments, and the ability to adhere to biological materials such as proteins. These materials are promising candidates, demonstrating potential applications in biosensing, cell imaging, diagnostics, and therapeutics. Preparation and exfoliation of 2D TMDs play an important part in these various applications as their properties are heavily dependent on the number of layers and lateral size. Described in this article are protocols for the liquid exfoliation of 2D TMDs from their bulk materials. Additional protocols are also provided for functionalizing or modifying the surface of the exfoliated 2D TMDs. (c) 2016 by John Wiley & Sons, Inc. PMID- 27258690 TI - Combinatorial Library Screening Coupled to Mass Spectrometry to Identify Valuable Cyclic Peptides. AB - Combinatorial library screening coupled to mass spectrometry (MS) analysis is a practical approach to identify useful peptides. Cyclic peptides can have high biological activity, selectivity, and affinity for target proteins, and high stability against proteolytic degradation. Here we describe two strategies to prepare combinatorial libraries suitable for MS analysis to accelerate the discovery of cyclic peptide structures. Both approaches use ChemMatrix resin and the linker 4-hydroxymethylbenzoic acid. One strategy involves the synthesis of a one-bead-two-peptides library in which each bead contains both the cyclic peptide and its linear counterpart to facilitate MS analysis. The other protocol is based on the synthesis of a cyclic depsipeptide library in which a glycolamidic ester group is incorporated by adding glycolic acid. After library screening, the ring is opened and the peptide is released simultaneously for subsequent MS analysis. (c) 2016 by John Wiley & Sons, Inc. PMID- 27258691 TI - Optogenetic Control of Nuclear Protein Import in Living Cells Using Light Inducible Nuclear Localization Signals (LINuS). AB - Many biological processes are regulated by the timely import of specific proteins into the nucleus. The ability to spatiotemporally control the nuclear import of proteins of interest therefore allows study of their role in a given biological process as well as controlling this process in space and time. The light inducible nuclear localization signal (LINuS) was developed based on a natural plant photoreceptor that reversibly triggers the import of proteins of interest into the nucleus with blue light. Each LINuS is a small, genetically encoded domain that is fused to the protein of interest at the N or C terminus. These protocols describe how to carry out initial microscopy-based screening to assess which LINuS variant works best with a protein of interest. (c) 2016 by John Wiley & Sons, Inc. PMID- 27258692 TI - Does Conversion Adversely Impact the Clinical Outcomes for Patients with Complicated Appendicitis? AB - BACKGROUND: Although the feasibility of laparoscopic appendectomy (LA) in complicated appendicitis (CA) has been demonstrated, LA is typically underused in CA due to its high conversion rate. However, little is known regarding the clinical course of conversion in CA. MATERIALS AND METHODS: Between January 2005 and April 2012, 1699 patients older than 16 years underwent an appendectomy at our institution. Of these, 207 were confirmed to have CA, which was defined as operative findings of gangrenous or perforated appendix, with or without abscess formation. Patients were divided into the following three groups: open group (OG), laparoscopy group (LG), and converted group (CG). Perioperative outcomes were compared between the three groups. RESULTS: Thirty-eight patients underwent open surgery. Among the 169 patients for whom laparoscopic surgery was originally attempted, 20 (11.8%) were converted. Operation time was significantly longer and estimated blood loss was higher in the CG than in the other groups. Fewer overall complications were observed and the length of hospital stay (LOH) was shorter in the LG than in the OG and CG. However, no significant differences were observed between the OG and CG regarding the overall complication rate or LOH. Operation method was the only factor associated with postoperative morbidity in multivariate analysis. CONCLUSION: While completion by laparoscopy was associated with better outcomes than the other two procedures at all levels, open conversion did not increase the overall morbidity or LOH compared with open appendectomy. Laparoscopic approach could be a viable option even in the management of CA. PMID- 27258694 TI - Trials of a Contralateral Hearing Aid After Long-Term Unilateral Cochlear Implant Use in Early-Onset Deafness. AB - PURPOSE: The purpose of this study was to evaluate the practicability of binaural hearing by adding a contralateral hearing aid (HA) after long-term cochlear implant (CI) use in prelingually deaf adults. METHOD: Five individuals with 1 CI volunteered for a 3-week bimodal (CI + HA) trial. HA gain was set low until sound was tolerable, then increased as listeners acclimated. Participants logged their daily listening experiences and were closely monitored by the audiologist. Measures included pre- and posttrial consonant-nucleus-consonant (CNC) word and phoneme scores and self-reports of satisfaction and listening ability in difficult situations. RESULTS: Acoustic stimulation was initially unpleasant, but approached comfort at target gain within the 3-week period. Benefit was demonstrated in continued voluntary HA use and higher bimodal phoneme scores compared to CI alone (8%-31% increases) for 4 of the participants. CONCLUSIONS: When a second CI is not a consideration, a contralateral HA should be pursued as the standard of care for prelingually deaf adults despite substantial auditory deprivation in the previously unaided ear, unpleasant sensations at initial HA fit, or lack of dramatic objective test gains. Frequent audiologist contact, repeated HA adjustments, and client journals are valuable in promoting favorable outcomes with bimodal hearing (adaptation, acceptance, and benefit) for this population. PMID- 27258695 TI - Assessment of Nonmotor Fluctuations Using a Diary in Advanced Parkinson's disease. AB - BACKGROUND: Since previous studies aimed to study nonmotor symptom (NMS) fluctuations in direct conjunction with motor oscillations, there are no data available on the temporal context of NMS fluctuations and motor oscillations in advanced Parkinson's disease (PD). OBJECTIVE: To evaluate circadian patterns and temporal connections of NMS and motor fluctuations in PD. METHODS: 15 controls, 17 non-fluctuating and 15 fluctuating PD patients completed two diaries by rating 4 key psychiatric (anxiety, depressive mood, inner restlessness, concentration/attention deficits), fatigue and 4 autonomic NMS (excessive sweating, sialorrhea, bladder urgency, dizziness) absent or present and motor function (Off, On with/without dyskinesia, and asleep) for every hour for 5 consecutive days. RESULTS: NMS Off state hours (hours with NMS rated as present) were less frequent compared to motor Off state hours and NMS On-Off-switches were less prevalent compared to those of the motor state. Off time and number of On Off-switches of psychiatric NMS were moderately correlated with motor Off time and number of motor On-Off switches on the individual patient level. Changes in NMS state occurred largely independent of changes in motor states with concordance rates of only 26-43% of all NMS changes for psychiatric and 7-17% for autonomic NMS. In controls and non-fluctuating PD patients, there were no NMS state switches in concordance to motor state switches. CONCLUSION: We provide first data on the temporal context of NMS fluctuations showing similar frequencies of psychiatric NMS Off, fatigue Off and motor Off times as well as their On-Off-fluctuations, but low concordance rates of NMS with motor On-Off state switches. We found no evidence for NMS fluctuations in non-fluctuating PD patients. Our data implicate similar fluctuation patterns of mood NMS and motor function without close timing and/or different kinetics. PMID- 27258693 TI - The Arabidopsis thaliana mobilome and its impact at the species level. AB - Transposable elements (TEs) are powerful motors of genome evolution yet a comprehensive assessment of recent transposition activity at the species level is lacking for most organisms. Here, using genome sequencing data for 211 Arabidopsis thaliana accessions taken from across the globe, we identify thousands of recent transposition events involving half of the 326 TE families annotated in this plant species. We further show that the composition and activity of the 'mobilome' vary extensively between accessions in relation to climate and genetic factors. Moreover, TEs insert equally throughout the genome and are rapidly purged by natural selection from gene-rich regions because they frequently affect genes, in multiple ways. Remarkably, loci controlling adaptive responses to the environment are the most frequent transposition targets observed. These findings demonstrate the pervasive, species-wide impact that a rich mobilome can have and the importance of transposition as a recurrent generator of large-effect alleles. PMID- 27258696 TI - Functional Status of Elderly Nursing Home Residents With Parkinson's Disease. AB - BACKGROUND: Parkinson's disease (PD) is a debilitating neurological disorder that has a significant impact on activities of daily living (ADL). Limited data exists regarding the functional status of nursing home residents with PD. OBJECTIVE: The study examined the nature, extent, and predictors of limitation of ADL in patients with PD residing in nursing homes. METHODS: This study used cross sectional design involving data from the National Nursing Home Survey (NNHS). The dependent variable was the total number of ADL for which the patient needed assistance. Assistance for ADL comprised of five items of transferring, dressing, eating, toileting and bathing. Multivariable linear regression was used to examine the individual, biological and environmental factors associated with assistance needed for ADL. RESULTS: The nationally representative study sample was of 98,093 nursing home residents with PD for an overall prevalence of 6.57%. The mean age of the study sample was 81.03+/-0.34 years. Mood symptoms (45%), behavioral symptoms (24%)and dementia (8%) were common among PD patients. Assistance needed for each ADL ranged from 68.24% for eating to 99.25% for bathing. Older age, being married, living in metropolitan statistical area (MSA), living in other place prior to admission, and presence of mood symptoms were positively related to assistance for ADL. Presence of behavioral symptoms and use of levodopa combination therapy were negatively related to assistance for ADL. CONCLUSIONS: Majority of the nursing home residents with PD had disability in all the five items of ADL. Various individual, environmental and biological factors were associated with ADL in nursing home residents with PD. PMID- 27258698 TI - Potential Benefit of Singing for People with Parkinson's Disease: A Systematic Review. AB - BACKGROUND: There is evidence that participation in performing arts brings psychosocial benefits in the general population and in recent years there has been substantial interest in the potential therapeutic benefit of performing arts, including singing, for people with chronic medical conditions including those of neurological aetiology. OBJECTIVE: To systematically review the existing body of evidence regarding the potential benefit of singing on clinical outcomes of people with PD. METHODS: Seven online bibliographic databases were systematically searched in January 2016 and supplementary searches were conducted. Full-text original peer-reviewed scientific papers that investigated the potential benefit of singing on at least one of speech, functional communication, cognitive status, motor function and quality of life in human participants with PD were eligible for inclusion. RESULTS: 449 unique records were identified, 25 full-text articles were screened and seven studies included in the review. All seven studies assessed the impact of singing on speech, five found partial evidence of benefit and two found no evidence of benefit. One study assessed each of functional communication and quality of life and no significant benefit was found. No included study assessed the impact of singing on motor function or cognitive status. CONCLUSIONS: Singing may benefit the speech of people with PD, although evidence is not unequivocal. Further research is required to assess wider benefits including on functional communication, cognitive status, motor function and quality of life. Substantial methodological limitations were identified in the existing literature. Recommendations are made for advancing the state of the literature. PMID- 27258699 TI - Suitability of the Depression, Anxiety, and Stress Scale in Parkinson's Disease. AB - BACKGROUND: The Depression, Anxiety, and Stress Scale -21 (DASS-21) is a frequently used measure of emotional disturbance symptoms in Parkinson's disease (PD). However, the factor structure of the DASS-21 in PD has yet to be explored. OBJECTIVE: To assess whether the scale is measuring these symptoms in PD in the same way as the general population. METHODS: The present study fit a series of established DASS-21 factor structures with both confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM) using data from 251 participants with PD. RESULTS: The 3-factor ESEM provided the best fit. The depression and stress scales fit well, however, few items on the anxiety subscale loaded clearly, with several items significantly loading onto the depression or stress factors. CONCLUSIONS: Whilst the depression and stress subscales appear suitable in PD, poor loadings and internal consistency indicate the anxiety subscale may not accurately assess anxiety symptomology in PD. This may be due to the scale's reliance on physiological symptoms as indicators of anxiety, when many of these are present in PD. Thus, the anxiety subscale of the DASS-21 may not be a suitable measure of anxiety in PD. PMID- 27258701 TI - The influence of hydration state on thermoregulation during a 161-km ultramarathon. AB - It is advised that individuals should avoid losing >2% of their body mass during exercise in order to prevent hyperthermia. This study sought to assess whether a loss of >2% body mass leads to elevations in core temperature during an ultramarathon. Thirty runners agreed to take part in the study. Body mass and core temperature were measured at the start, at three locations during the race and the finish. Core temperature was not correlated with percent body mass change (p = 0.19) or finish time (p = 0.11). Percent body mass change was directly associated with finish time (r = 0.58, p < 0.01), such that the fastest runners lost the most mass (~3.5-4.0%). It appears that a loss of >3% body mass does not contribute to rises in core temperature. An emphasis on fluid replacement for body mass losses of this magnitude during prolonged exercise is not justified as a preventative measure for heat-related illnesses. PMID- 27258700 TI - The Key Determinants to Quality of Life in Parkinson's Disease Patients: Results from the Parkinson's Disease Biomarker Program (PDBP). AB - BACKGROUND: The impact of motor- and non-motor symptoms on health-related quality of life (HRQOL) in Parkinson's disease (PD) has received increasing attention. OBJECTIVES: To address this, the study explored a large cohort of patients enrolled in the PD Biomarker Program. METHODS: The PD Questionnaire-39 (PDQ-39) measured HRQOL, whereas the Unified PD Rating Scale (UPDRS) assessed motor and non-motor symptoms. Determinants of HRQOL in PD patients were identified by stepwise linear regression analysis. The relationship between the PDQ-39 and UPDRS subscale scores then was explored through structural equation modeling. RESULTS: The mean disease duration was 6.8 years and the mean PDQ-39 summary index (PDQ-39SI) was 18.4. UPDRS-I (non-motor function) and UPDRS-II (motor questionnaire) scores demonstrated the strongest correlations with PDQ-39SI (r ? 0.4, P < 0.05), whereas UPDRS-III (motor exam) and UPDRS-IV (motor complications) scores were correlated moderately with PDQ-39SI (0.3 < r < 0.4, P < 0.05). Multiple linear stepwise regression analyses showed that age (beta= -0.13, P < 0.001), education (beta= -0.07, P = 0.008), UPDRS-I (beta= 0.32, P = 0.000), and UPDRS-II (beta= 0.44, P < 0.001) significantly contributed to HRQOL, and cumulatively accounted for 69.1% of the PDQ-39SI variance. UPDRS-II score was the primary predictor of PDQ-39SI, accounting for 57.3% of the variance, whereas UPDRS-I score accounted for 7.5%. UPDRS-III and -IV and other factors measured did not survive stepwise regression. Structural equation modeling confirmed the association of UPDRS-II (beta= 0.67, P < 0.001) and UPDRS-I (beta= 0.35, P < 0.001) with the PDQ-39SI. CONCLUSION: Both motor and non-motor function scores impacted significantly HRQOL in PD. UPDRS-III, however, has limited contributions to HRQOL although it is used as a main outcome in many clinical trials. PMID- 27258697 TI - Structural Imaging and Parkinson's Disease: Moving Toward Quantitative Markers of Disease Progression. AB - Parkinson's disease (PD) is a progressive age-related neurodegenerative disorder. Although the pathological hallmark of PD is dopaminergic cell death in the substantia nigra pars compacta, widespread neurodegenerative changes occur throughout the brain as disease progresses. Postmortem studies, for example, have demonstrated the presence of Lewy pathology, apoptosis, and loss of neurotransmitters and interneurons in both cortical and subcortical regions of PD patients. Many in vivo structural imaging studies have attempted to gauge PD related pathology, particularly in gray matter, with the hope of identifying an imaging biomarker. Reports of brain atrophy in PD, however, have been inconsistent, most likely due to differences in the studied populations (i.e. different disease stages and/or clinical subtypes), experimental designs (i.e. cross-sectional vs. longitudinal), and image analysis methodologies (i.e. automatic vs. manual segmentation). This review attempts to summarize the current state of gray matter structural imaging research in PD in relationship to disease progression, reconciling some of the differences in reported results, and to identify challenges and future avenues. PMID- 27258702 TI - Closed-System One-Pot Block Copolymerization by Temperature-Modulated Monomer Segregation. AB - A biphasic one-pot polymerization method enables the preparation of block copolymers from monomers with similar and competitive reactivities without the addition of external materials. AB diblock copolymers were prepared by encapsulating a frozen solution of monomer B on the bottom of a reaction vessel, while the solution polymerization of monomer A was conducted in a liquid layer above. Physical separation between the solid and liquid phases permitted only homopolymerization of monomer A until heating above the melting point of the lower phase, which released monomer B, allowing the addition of the second block to occur. The triggered release of monomer B allowed for chain extension without additional deoxygenation steps or exogenous monomer addition. A method for the closed (i.e., without addition of external reagents) one-pot synthesis of block copolymers with conventional glassware using straightforward experimental techniques has thus been developed. PMID- 27258704 TI - Update on Screening Recommendations for Hydroxychloroquine Retinopathy. PMID- 27258705 TI - Demystifying the Role of Nonsurgical Treatment in Advanced Supraglottic Carcinoma. PMID- 27258703 TI - A glass menagerie of low complexity sequences. AB - Remarkably simple proteins play outsize roles in the execution of developmental complexity within biological systems. Sequence information determines structure and hence function, so how do low complexity sequences fulfill their functions? Recent discoveries are raising the curtain on a new dimension of the sequence structure paradigm. In it, function derives not from the structures of individual proteins, but instead, from dynamic material properties of entire ensembles of the proteins acting in unison through phase changes. These phases include liquids, one-dimensional crystals, and - as elaborated herein - even glasses. The peculiar thermodynamics of glass-like protein assemblies, in particular, illuminate new principles of information flow through and, at times, orthogonal to the central dogma of molecular biology. PMID- 27258706 TI - Caudal Septal Support Versus Strut Graft in Achieving the Desired Lateral Profile in Rhinoplasty. AB - Nasal tip support is critical to achieve a lasting result in rhinoplasty. In this article, the authors compared the effects of strut grafts (SG) and caudal septum based nasal tip supporting techniques (CSB-T) in terms of reaching the desired tip projection.Included in this study were 40 patients (24 women and 16 men) who underwent primary open rhinoplasty via transcolumellar incision between January and June 2012. To achieve a good nasal projection, SG and CSB-T were used for 15 and 25 of these patients, respectively.Certain anatomic landmarks were identified on preoperative, simulative, and 1-year follow-up photos. With these landmarks, certain angular and proportional values were calculated.In the SG, the authors found no statistically significant difference in between simulative goals and postoperative results regarding bending angle. Postoperative nasolabial angle (NLA), tip angle, subnasal-tip/subnasal-radix (SnT/SnR) ratios were significantly lower than the simulation values; radix angle and supratip index values were significantly higher.In the CSB-T group, the authors found no statistically significant difference in between preoperative values and postoperative results regarding NLA, tip angle, bending angle, (SnT/SnR) ratio values. Postoperative supratip index and radix angle measurements were found to be significantly higher than the simulation values.With these findings, the authors concluded that CSB-T support is superior than the SG for supporting the nasal tip in noses that also need shortening in caudal length. In noses that do not need caudal shortening, nasal tip projection can again be supported by the caudal septum by just forming a bridge between lower lateral cartilage and quadrangular septum using a wider SG that mimics septal extension grafts. PMID- 27258707 TI - Guideline for the Treatment of Condylar Osteochondroma Combined With Secondary Dentofacial Deformities. AB - OBJECTIVE: Surgical treatment of condylar osteochondroma combined with secondary dentofacial deformities is a significant clinical challenge. The authors present this review article to provide some guidelines for the surgical treatment for this severely complex condition. MATERIALS AND METHODS: Diagnosis and treatment protocol of condylar osteochondroma patients combined with secondary dentofacial deformities are discussed at the basis of published literatures and the authors' own clinical experiences. Proper treatment protocol was designed according to features of tumor and dentofacial deformities. Follow-up and radiographic examination was performed to evaluate recurrence of tumor, occlusion, joint function, and facial appearance after surgery. RESULTS: The patients received 1 or several methods of resection of tumor, condylar reconstruction, correction of skeletal deformities, and treatment of malocclusion. The condylar ostechondroma and secondary dentofacial deformities were treated satisfactorily. Temporomandibular joint function, occlusion, and facial appearance were improved obviously after operation evidenced by radiographic examination and follow-up. CONCLUSION: Surgical management of condylar osteochondroma with secondary dentofacial deformities requires careful patient selection, treatment planning, and precise execution. This article has reviewed the current status of surgical treatment options and provided practical guidelines for oral and maxillofacial surgeons to consider their clinical practice. PMID- 27258708 TI - Clinical Results of Modified Frontalis Suspension Technique Using Preserved Fascia Lata for Congenital Ptosis. AB - PURPOSE: The purpose of this study was to evaluate the clinical results of modified frontalis suspension technique with preserved fascia lata and to analyze the results according to age and preoperative ptosis degree. METHODS: This study involved a retrospective review of the electronic medical records of congenital ptosis patients who underwent unilateral or bilateral frontalis sling surgery using preserved fascia lata between March 1, 2004 and December 31, 2012. RESULTS: Seventy-seven patients (99 eyes) were included in the study. The mean age of the patients at the time of surgery was 6.2 +/- 6.7 years. Mean follow-up time was 5.4 +/- 3.2 years. Among 77 patients, 22 patients (28.5%) had a mild degree of ptosis, 39 (50.6%) had moderate, and 16 (20.7%) had a severe degree of ptosis. A satisfactory result (good and fair) was achieved in 65 of the 77 patients (84.4%) and a poor result was recorded in 12 patients (15.5%). Preoperative ptosis degree had no effect on the surgical success rate (19/22 [86.3%] in the mild group versus 34/39 [87.1%] in the moderate group versus 12/16 [75%] in the severe group, P = 0.243). There was no significant difference in surgical success rate between the unilateral and bilateral ptosis groups (45/55 [81.8%] versus 20/22 [90.9%], P = 0.479 respectively), between sexes (41/46 [89.1%] in male versus 24/31 [77.4%] in female, P = 0.271), or age groups (52/60 [86.6%] in younger group versus 13/17 [76.4%] in elder group, P = 0.526). Recurrence of ptosis did not differ according to the preoperative ptosis degree (3/22 [13.6%] in the mild group, 5/39 [12.8%] in the moderate group, and 2/16 [12.5%] in the severe group, P = 0.994). Age also had no influence on the ptosis recurrence. The preoperative marginal reflex distance 1 of 0.41 +/- 1.06 mm increased to 1.67 +/- 0.80 mm postoperatively (P = 0.000). CONCLUSIONS: The authors identified the long-term efficacy of preserved fascia lata in frontalis sling surgery with a modified frontalis suspension method for all age groups of patients. There was a small rate of recurrence (12.9%) over a maximum of 9 years of follow-up, which was corrected with additional surgery. PMID- 27258709 TI - Analysis of Surgical Outcome After Levator Advancement by Assessing Changes in Eyelid Contour. AB - PURPOSE: The authors analyzed changes in eyelid contour after levator advancement by measuring multiple radial midpupil lid distance (MPLD). METHODS: The study enrolled 61 eyes of 61 patients with involutional ptosis who underwent levator advancement from 2 oculoplastic surgeons from September 2008 to December 2013. An analysis of upper lid contours was performed using front gaze photographs of the preoperative and postoperative states and comparing them to the front gazes of normal patients. Conventional and 12 oblique midpupil lid distances were measured every 15 degrees across the temporal (105, 120, 135, 150, 165, and 180 degrees) and nasal (75, 60, 45, 30, 15, and 0 degrees) fields of the eyelid fissure using custom software. RESULTS: Ptosis patients had low temporal eyelid height and significantly decreased MPLD at all angles compared with normal controls. Compared with the preoperative eyelid, all MPLD angles were significantly increased after surgery, and the temporal peak height of the eyelid was recovered. CONCLUSIONS: The normal shape and temporal peak height of eyelids should be considered for levator advancement surgery with ptosis. The authors retrospectively compared postoperative changes in eyelid contour to modify the method of surgery. PMID- 27258710 TI - Intraoperative Pulsed Expansion of the Skin Using Silicone Urinary Catheter for the Placement of Osmotic Expander. PMID- 27258711 TI - Surgical Outcomes of Deep Superior Sulcus Augmentation Using Acellular Human Dermal Matrix in Anophthalmic or Phthisis Socket. AB - Patients with anophthalmic or phthisis socket suffer from cosmetic problems. To resolve those problems, the authors present the surgical outcomes of deep superior sulcus (DSS) augmentation using acellular dermal matrix in patients with anophthalmic or phthisis socket. The authors retrospectively reviewed anophthalmic or phthisis patients who underwent surgery for DSS augmentation using acellular dermal matrix. To evaluate surgical outcomes, the authors focused on 3 aspects: the possibility of wearing contact prosthesis, the degree of correction of the DSS, and any surgical complications. The degree of correction of DSS was classified as excellent: restoration of superior sulcus enough to remove sunken sulcus shadow; fair: gain of correction effect but sunken shadow remained; or fail: no effect of correction at all. Ten eyes of 10 patients were included. There was a mean 21.3 +/- 37.1-month period from evisceration or enucleation to the operation for DSS augmentation. All patients could wear contact prosthesis after the operation (100%). The degree of correction was excellent in 8 patients (80%) and fair in 2. Three of 10 (30%) showed complications: eyelid entropion, upper eyelid multiple creases, and spontaneous wound dehiscence followed by inflammation after stitch removal. Uneven skin surface and paresthesia in the forehead area of the affected eye may be observed after surgery. The overall surgical outcomes were favorable, showing an excellent degree of correction of DSS and low surgical complication rates. This procedure is effective for patients who have DSS in the absence or atrophy of the eyeball. PMID- 27258712 TI - Outcomes of Anatomic Reconstruction of Gunshot-Inflicted Lower Face Defects by Free Osteoseptocutaneous Fibula Flap and Expanded or Nonexpanded Temporal Scalp Flap Combination in Males. AB - Reconstruction of gunshot-inflicted composite lower face defects is a challenge for plastic surgeons. Functional and aesthetic repair of such defects mostly requires free or pedicled flap applications or combinations of both.In this study, the authors evaluated 7 males with gunshot-inflicted composite mandibular defects. All patients underwent reconstruction with a free osteoseptocutaneous fibula flap (FOCF) for the composite mandibular defect and a pre or nonexpanded temporal artery-based scalp flap for beardless facial skin. All patients were evaluated aesthetically and functionally with a postoperative evaluation scale. Average patient follow-up time was 3.5 years.All FOCFs survived completely. Expander exposition was observed in 2 preexpanded temporal scalp flaps. The problem was solved by rapid expansion and early flap application. All patients had acceptable functional and aesthetic results.In conclusion, the scalp flap should be considered in male beardless skin reconstruction due to its ease of application, reliability, and proximity to the defect. Preexpansion of this flap can decrease donor area morbidities. Moreover, the FOCF and scalp flap combination is a convenient procedure for gunshot-inflicted lower face defects, and such procedures produce good aesthetic and functional long-term outcomes. PMID- 27258713 TI - Can Platelet Indices Be New Biomarkers for Subjective Tinnitus? AB - OBJECTIVES: Mean platelet volume (MPV) is one of the platelet function indices that reflect the platelet production rate and functions. The MPV levels are increased by vascular occlusion, acute or chronic syndromes, and vasculitis, whereas infections, autoimmune diseases, and inflammatory situations reduce these levels. In this study, the authors investigated whether there was a relationship between platelet indices and subjective tinnitus. METHODS: In this retrospective study, the authors evaluated platelet indices in subjective tinnitus patients. One hundred patients with subjective tinnitus and 100 healthy, age and sex matched subjects were enrolled to the study. Audiometer and laboratory results were recorded. Comparative multivariate analyses between indicator factors and hearing outcomes were conducted. RESULTS: Mean platelet volume is significantly lower in subjective tinnitus group (P < 0.001). Platelet count and platelet distribution width are higher in the subjective tinnitus than control group (P < 0.001, P < 0.003, respectively). CONCLUSION: The authors' findings indicate that subjective tinnitus appears to be characterized by autoimmune and inflammatory events. Considering the decreasing MPV levels, MPV may be used to evaluate subjective tinnitus as an helper indicator. PMID- 27258716 TI - Morphometrics of the Anterior Belly and Intermediate Tendon of the Digastric Muscle: Sexual Dimorphism and Implications for Surgery. AB - The anterior belly of the digastric muscle (ABDM) is important in a variety of surgeries including submental lipectomy, rhytidectomy, alteration of the cervicomental angle via muscle resection, the "digastric corset" procedure for submental rejuvenation, the submental artery flap, and reanimation of the mouth after facial nerve palsy. Despite its clinical significance, little information exists regarding the morphometrics of the ABDM or its associated intermediate tendon. This study analyzed a total of 35 intact ABDMs and 43 intact intermediate tendons from 23 cadavers. Measurements were taken of the following parameters: muscle belly area, muscle belly length, intermediate tendon length, and intermediate tendon width at mid-tendon. Normative descriptive statistics are included within the report. Males were found to have significantly longer left sided muscle bellies than right-sided bellies from males (U = 23.0; P = 0.044), left-sided bellies from females (U = 19.0; P = 0.020), and right-sided bellies from females (U = 12.0; P = 0.035). The morphometry, including sexual dimorphism, presented in this report can aid in the surgical planning and execution of numerous operations performed in head and neck, especially digastric muscle transfer surgery. PMID- 27258717 TI - Use of Adipose-Derived Mesenchymal Stem Cells to Increase Viability of Composite Grafts. AB - OBJECTIVE: Chondrocutaneous composite grafts figure among the reconstruction alternatives for alar rim defects resulting from tumor resection and trauma. The major problem with composite grafts is the limited graft survival area. In the present study, the authors aimed to increase the survival area of composite grafts by utilizing the ability of stem cells to promote neovascularization which is crucial in composite graft viability. METHODS: The study included 36 adult Wistar Albino rats, which were allocated to 6 groups. Groups 1, 2, and 3 were the groups in which the grafts were implanted immediately after the defect was formed, and Groups 4, 5, and 6 were those in which grafts were adapted 4 days after the defect was formed. Composite grafts of 1 * 1 cm containing both the cartilage and the skin were prepared from 1 ear, and after forming punctures and incisions on the cartilage, the grafts were adapted to the 1 * 1 cm defects on the back. The backs of the rats in groups 1 and 4 were injected with adipose derived stem cell (ADSC), those in groups 2 and 5 with medium solution, while the rats in Groups 3 and 6 did not receive any injection. The procedures were followed by histopathological and scintigraphic evaluations. RESULTS: An evaluation of the statistical results showed that composite graft survival areas of the group treated with stem cells increased significantly, in comparison with control and medium groups. When scintigraphic evaluations were considered, it was seen that the group treated with stem cells had significantly higher radioactive substance retention than the control group. Histopathological examination demonstrated that microscopic survival rates in the stem cell group were higher than those in the control group. Green fluorescent protein (GFP) was used in the experiment to tag adipose tissue-derived stem cells. Immunofluorescence staining studies showed less apoptosis and fewer GFP (+) stem cells in the composite grafts of the stem cell group. However, apoptosis was more severe in the control and medium groups which also had decreased vascularity in the graft. DISCUSSION: As the authors have shown in the present study, ADSCs have favorable effects on the viability of composite grafts. They have increased the survival rate of the grafts to a considerable extent. As a clinical implication of this experimental study, the authors think that in the patient of auricular and nasal defects involving the cartilage and the skin, injection of the ADSC and the adaptation of composite grafts 4 days after the preparation of the receiving bed may increase the composite graft viability rates. Thus, it has been found that if the composite grafts are implanted 4 days after stem cell injection, the injection of adipose tissue-derived mesenchymal stem cells is useful in enhancing the survival of composite grafts. PMID- 27258718 TI - Hair Today; Scalped Tomorrow: Massive Subgaleal Haematoma Following Sudden Hair Pulling in an Adolescent in the Absence of Haematological Abnormality or Skull Fracture. AB - Subgaleal haematoma (SH) is a rare condition, most frequently observed in neonates as a complication of Ventouse-assisted delivery. There have been few patients reported beyond this period. Those that are present within the literature have typically resulted from significant blunt scalp trauma, with or without associated skull fracture. Those resulting secondary to relatively minor trauma, such as hair braiding or hair pulling, are rare but have been reported and are often associated with underlying haematological abnormalities or nonaccidental injury patients. Most patients resolve spontaneously and without complication. The authors report a rare patient of a delayed presentation of a massive SH in an adolescent following a seemingly innocuous episode of hair pulling whilst play-fighting, in the absence of any underlying haematological or anatomical abnormality. Due to the size of the SH and the appearance of large areas of calcification within the haematoma, early liaison with senior neuroradiologists and haematologists, to rule out underlying anatomical and haematological abnormalities, respectively, was essential to guide appropriate management. Our patient highlights the need for an awareness of the possible aetiologies of SH and the necessity of early active multidisciplinary team involvement in the management of such patients, which is critical to ensure optimum patient outcomes. PMID- 27258719 TI - Correlation of Age, Sex, and Location With Recurrence of Oral Giant Pyogenic Granuloma After Surgical Excision. AB - OBJECTIVES: This study was carried out to correlate age and sex of the patient as well as location of the oral giant pyogenic granuloma (PG) with the recurrence rate after surgical excision. METHODS: Seventy-two patients having oral giant PGs were treated by a conservative surgical excision. Information on sex, age, lesion site, and recurrence was collected. Data were reviewed and analyzed to correlate the recurrence rate with sex and age of the patient as well as the location of the lesion. RESULTS: Recurrence of the oral giant PG was occurred in 22.2% of patients. The highest rates of recurrence were observed in the third (33.3%) and fourth (19%) decades of life. The recurrence rate was more common in females (24%) than males (18.2%) and it was predominant in mandibular lesions (25%) than maxillary one (8.3%). CONCLUSIONS: On the basis of their results the authors concluded that recurrence of oral giant PG has an obvious correlation with age and sex of the patient as well as location of the lesion. PMID- 27258720 TI - Overcommitment as a predictor of effort-reward imbalance: evidence from an 8-year follow-up study. AB - OBJECTIVE: The effort-reward imbalance (ERI) model includes the personal characteristic of overcommitment (OC) and the job-related characteristics of effort, reward, and ERI, all of which are assumed to play a role in an employee's health and well-being at work. The aim of the present longitudinal study was to shed more light on the dynamics of the ERI model by investigating the basic hypotheses related to the role of OC in the model, ie, to establish whether an employee's OC could be a risk factor for an increased experience of high effort, low reward, and high ERI at work. METHODS: The study was based on 5-wave, 8-year follow-up data collected among Finnish professionals in 2006 (T1, N=747), 2008 (T2, N=422), 2010 (T3, N=368), 2012 (T4, N=325), and 2014 (T5, N=273). The participants were mostly male (85% at T1) and the majority of them worked in technical fields. OC, effort, reward, and ERI were measured at each time point with the 23-item ERI scale. RESULTS: Three cross-lagged structural equation models (SEM) were estimated and compared by using full information maximum likelihood method: (i) OC predicted later experiences of effort, reward, and ERI (normal causation model), (ii) effort, reward, and ERI predicted later OC (reversed causation model), and (iii) associations in normal causal and reversed causal models were simultaneously valid (reciprocal causation model). The results supported the normal causation model: strong OC predicted later experiences of high effort, low reward and high ERI. CONCLUSIONS: High OC is a risk factor for an increased experience of job strain factors; that is, high effort, low reward, and high ERI. Thus, OC is a risk factor not only for an employee's well-being and health but also for an increasing risk for perceiving adverse job strain factors in the working environment. PMID- 27258722 TI - How social is the chaser? Neural correlates of chasing perception in 9-month-old infants. AB - We investigated the neural correlates of chasing perception in infancy to determine whether animated interactions are processed as social events. By using EEG and an ERP design with animations of simple geometric shapes, we examined whether the positive posterior (P400) component, previously found in response to social stimuli, as well as the attention related negative fronto-central component (Nc), differs when infants observed a chaser versus a non-chaser. In Study 1, the chaser was compared to an inanimate object. In Study 2, the chaser was compared to an animate but not chasing agent (randomly moving agent). Results demonstrate no difference in the Nc component, but statistically higher P400 amplitude when the chasing agent was compared to either an inanimate object or a random object. We also find a difference in the N290 component in both studies and in the P200 component in Study 2, when the chasing agent is compared to the randomly moving agent. The present studies demonstrate for the first time that infants' process correlated motion such as chasing as a social interaction. The perception of the chasing agent elicits stronger time-locked responses, denoting a link between motion perception and social cognition. PMID- 27258723 TI - Biological Effects of Temsirolimus on the mTOR Pathway in Endometrial Carcinoma: A Pharmacodynamic Phase II Study. AB - OBJECTIVE: The PI3K/AKT/mTOR pathway is frequently aberrantly activated in endometrial carcinoma (EC). Temsirolimus is an mTOR inhibitor that has shown clinical activity in EC. We aimed to characterize the biological effects on mTOR pathway of temsirolimus in treatment-naive patients with primary EC, and to identify potential biomarkers associated with a short-term exposure to temsirolimus. MATERIALS AND METHODS: Patients with EC were treated with 4 doses of temsirolimus previous to surgery. The primary objective was the analysis of paired endometrial aspirates and posttreatment (hysterectomy specimens) tumor tissue samples for mTOR downstream effectors p-S6K1 and p-4BEP1 levels by immunohistochemistry. Secondary objectives included analysis of expression of other mTOR-related biomarkers by immunohistochemistry, as well as analysis of the predictive value of mutations in mTOR-related genes. Toxicity was also assessed. RESULTS: Eleven patients were included in the study. p-S6K1 expression was reduced after treatment with temsirolimus in all patients. Variations of the expression of other mTOR-related proteins including p-4BEP1, PTEN, p-AKT, p53, p27, BAD, Bcl-2, Ki67, and cyclin D1 were also observed. Interestingly, the biological effects of the drug were more evident 1 week after the last dose of temsirolimus. Effects were less evident on tumors harboring mutations in NRAS. Toxicity was acceptable, being mucositis the most frequent adverse event. CONCLUSIONS: Short temsirolimus exposure effectively inhibits mTOR pathway in patients with endometrial cancer. p-S6K1 expression is a promising biomarker of sensitivity. The preoperative window opportunity in EC is a realistic scenario for biological knowledge and target development. PMID- 27258721 TI - Particulate Matter and Subclinical Atherosclerosis: Associations between Different Particle Sizes and Sources with Carotid Intima-Media Thickness in the SAPALDIA Study. AB - BACKGROUND: Subclinical atherosclerosis has been associated with long-term exposure to particulate matter (PM), but the relevance of particle size and sources of exposure remains unclear. OBJECTIVES: We investigated the association of long-term exposure to PM10 (<= 10 MUm), PM2.5 (<= 2.5 MUm: total mass, vehicular, and crustal sources), and ultrafine particles [UFP < 0.1 MUm: particle number concentration (PNC) and lung-deposited surface area (LDSA)] with carotid intima-media thickness (CIMT). METHODS: We used data from 1,503 participants >= 50 years old who participated in the third examination of the Swiss SAPALDIA cohort. Exposures were obtained from dispersion models and land-use regression models. Covariate information, including previous cardiovascular risk factors, was obtained from the second and third SAPALDIA examinations. RESULTS: The adjusted percent difference in CIMT associated with an exposure contrast between the 10th and 90th percentile was 1.58% (95% CI: -0.30, 3.47%) for PM10, 2.10% (95% CI: 0.04, 4.16%) for PM2.5, 1.67% (95% CI: -0.13, 3.48%) for the vehicular source of PM2.5, -0.58% (95% CI: -3.95, 2.79%) for the crustal source of PM2.5, 2.06% (95% CI: 0.03, 4.10%) for PNC, and 2.32% (95% CI: 0.23, 4.40%) for LDSA. Stronger associations were observed among diabetics, subjects with low educational level, and those at higher cardiovascular risk. CONCLUSIONS: CIMT was associated with exposure to PM10, PM2.5, and UFP. The PM2.5 source-specific analysis showed a positive association for the vehicular source but not for the crustal source. Although the effects of PNC and LDSA were similar in magnitude, two-pollutant and residual-based models suggested that LDSA may be a better marker for the health relevance of UFP. Citation: Aguilera I, Dratva J, Caviezel S, Burdet L, de Groot E, Ducret-Stich RE, Eeftens M, Keidel D, Meier R, Perez L, Rothe T, Schaffner E, Schmit-Trucksass A, Tsai MY, Schindler C, Kunzli N, Probst Hensch N. 2016. Particulate matter and subclinical atherosclerosis: associations between different particle sizes and sources with carotid intima-media thickness in the SAPALDIA study. Environ Health Perspect 124:1700-1706; http://dx.doi.org/10.1289/EHP161. PMID- 27258724 TI - Routine Intraoperative Frozen Section Examination to Minimize Bimodal Treatment in Early-Stage Cervical Cancer. AB - OBJECTIVE: In early-stage cervical cancer, single modality therapy is the main objective, to minimize patient morbidity while offering equivalent cure rates. Intraoperative frozen section examination (FSE) of lymph nodes (LNs) can facilitate this aim, ensuring that radical surgery is avoided in patients requiring adjuvant therapy for metastatic LN involvement. We aimed to evaluate the accuracy of routine intraoperative FSE of pelvic LNs during the surgical staging of early-stage cervical cancers and identify a group at low risk for nodal metastases. METHODS: A retrospective cohort study of 94 women aged 23 to 80 years who underwent primary surgery and planned intraoperative FSE of the pelvic LNs at the gynecological cancer center in Oxford was performed. The diagnostic value of FSE and the prediction of metastatic nodal disease were assessed by use of preoperative and intraoperative variables. RESULTS: A total of 1825 LNs were submitted for FSE. Of 94 women (13.8%), 13 had positive LNs at FSE. Two false negative cases were reported with micrometastases but no false-positive cases. Frozen section examination as a diagnostic test reached a sensitivity of 86.7% and a specificity of 100%. A regression model including grade I to II and tumor size of less than 20 mm identified a low-risk group for LN involvement. CONCLUSIONS: In light of diverse practice patterns, FSE should be routinely offered to women with early-stage cervical cancer in a 1-step protocol. We equally devised a model to predict those patients at least risk of nodal disease, who may be spared of FSE. PMID- 27258725 TI - DNA Methylation Signatures in Vaginal Fluid Samples for Detection of Cervical and Endometrial Cancer. AB - OBJECTIVE: A noninvasive tool that allows individuals to be monitored who are at risk of developing a malignancy is an unmet need. Such a test would need to consist of a molecular signature that allows for gradual judgment to assess the efficacy of preventive strategies. Here we performed a proof-of-principle study to test whether a DNA methylation (DNAme) signature in fluid collected from the vagina is able to identify women with cervical or endometrial cancer. MATERIALS AND METHODS: DNA from vaginal fluid samples from 111 women (30, 8, 73 with endometrial cancer, cervical cancer, and benign gynecological conditions, respectively) were analyzed for DNAme using the Illumina 450k DNA methylation bead array assay, which allows the assessment of DNAme at more than 480.000 CpG sites. We developed a cervical and an endometrial cancer DNAme signature by comparing normal and cancerous cervical and endometrial samples from the publicly available The Cancer Genome Atlas data and developed deviation scores to assess the potential of discriminating cancer from a control sample using a vaginal fluid DNAme signature. RESULTS: More than 60% of variations in DNAme in our vaginal fluid cannot be explained by those clinical or technical factors that we were aware of. Both the cervical and the endometrial cancer DNAme signature resulted in receiver operating characteristic area under the curve between 0.75 and 0.83 to discriminate controls and the cancers for which the signature has been designed for. CONCLUSIONS: Whole DNAme signatures based on array technologies in body fluids are able to discriminate cancer cases from controls. PMID- 27258726 TI - Gestational Trophoblastic Disease: Opportunities for a National Registry Collaboration. AB - OBJECTIVE: In rare entities such as gestational trophoblastic disease (GTD), only multi-institutional registries can gather significant number of patients to build up valuable clinical databases. No Canada-wide GTD registry currently exists. We conducted a survey among members of the Canadian Society of Gynecologic Oncology (GOC) to investigate their interest in a pan-Canadian GTD registry. We also took the opportunity to explore their management of GTD. METHODS: An electronic survey was conducted. The target group was the entire GOC Canadian Membership. The survey consisted of 25 questions. RESULTS: The survey participation rate was 39% (67/171). Seventy-six percent of responders treat patients with molar pregnancy or gestational trophoblastic neoplasia (GTN), and the majority treat only 5 or less cases of molar pregnancy and 5 or less cases of GTN per year. In cases of low-risk GTN, 80% of responders use generally recommended single-agent chemotherapy regimens. In cases of high-risk GTN, 76% use generally recommended multiagent chemotherapy regimens. Most respondents do not submit either molar pregnancy or GTN patients to any formal registry, although the vast majority (92%) would do so if they had access to a registry, given that most believe that a registry can or probably can help patients with GTD. Responders indicated that the jurisdiction of such a registry should be national (59%), provincial (25%), and regional (11%). CONCLUSIONS: Despite some variation, responders were generally knowledgeable about contemporary management issues. Canadian Society of Gynecologic Oncology members acknowledge generally low exposure to GTD patients in Canada and support the creation of a national GTD registry to facilitate optimal patient care, education, and research. PMID- 27258727 TI - Activity of Bevacizumab in Patients With Low-Grade Serous Ovarian Carcinoma. AB - OBJECTIVES: The aim of this study was to evaluate the antitumor activity of bevacizumab in low-grade serous ovarian carcinoma (LGSOC). METHODS: We retrospectively identified patients with LGSOC treated with bevacizumab. RESULTS: Twelve patients with LGSOC who received bevacizumab were identified. Eleven patients received bevacizumab alone. Only 1 (8.3%) of 12 patients had evidence of a partial response. Ten (90.9%) of the 11 patients were progression free at 6 months. All but 1 patient who received only 2 courses before treatment interruption had a progression-free survival (PFS) of greater than 6 months. The median PFS was 48 months (range, 5-123+ months). Three of the patients reported in this series had extended disease stabilization that lasted for 123+, 48, and 15+ months after progression-free intervals on prior chemotherapy regimens of 2.5, 4, and 7 months, respectively. The median overall survival was not reached at a median follow-up of 32 months, with only 1 of the 12 patients dying of disease. CONCLUSIONS: In our series, in patients with LGSOC treated primarily with bevacizumab, primarily as a single agent, a low response rate but very long PFS is observed. In addition, patients have had secondary PFS durations that exceeded their prior PFS, which is a sign of anticancer activity. PMID- 27258728 TI - Docosahexaenoic Acid Modulates Invasion and Metastasis of Human Ovarian Cancer via Multiple Molecular Pathways. AB - OBJECTIVE: We investigated the effect of docosahexaenoic acid (DHA) on the invasion and metastasis of ovarian cancer cells (A2780, HO8910, and SKOV-3). METHODS: Cytotoxicity assay was performed to determine the optimal doses of DHA in this experiment. The effects of DHA on invasion ability were assessed by invasion assay. The expressions of messenger RNA and/or proteins associated with invasion or metastasis were detected by quantitative Real Time-Polymerase Chain Reaction or Western blot. The effect of DHA on cell metastasis was assessed in xenograft model of zebrafish. RESULTS: Docosahexaenoic acid and alpha-linolenic acid could reduce the cell vitalities in dose-dependent manner. However, DHA inhibited the invasion and metastasis of ovarian cancer cells, but alpha linolenic acid did not (**P < 0.01). Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-gamma, which negatively correlated with cell invasion and metastasis (*P < 0.05). Docosahexaenoic acid restrained the development of subintestinal vessels and cancer cell metastasis in xenograft model of zebrafish (**P < 0.01). CONCLUSIONS: Docosahexaenoic acid inhibited the invasion and metastasis of ovarian cancer cells in vitro and in vivo through the modulation of NF-kappaB signaling pathway, suggesting that DHA is a promising candidate for ovarian cancer therapy. PMID- 27258729 TI - How Common Is the Growing Teratoma Syndrome in Patients With Ovarian Immature Teratoma? AB - OBJECTIVES: Growing teratoma syndrome (GTS) after adjuvant chemotherapy for ovarian germ cell tumors is uncommon, with approximately 60 cases reported in the English literature. The objective of this study was to report clinical parameters including outcomes of patients with a diagnosis of GTS after adjuvant chemotherapy for ovarian immature teratoma (IT). METHODS AND MATERIALS: Patients with a condition diagnosed as ovarian IT between 1999 and 2014 at 2 tertiary-care academic centers were evaluated for the development of GTS. Patients' demographics, surgical and pathology data, adjuvant treatment, tumor markers, and survival data were collected retrospectively. RESULTS: Twenty-six patients were treated for ovarian IT with a median follow-up of 69 months (9-166 months). Of the 15 patients who received adjuvant chemotherapy, 6 developed GTS (crude incidence, 40%; 2- and 5-year cumulative actuarial rates, 40% and 50%, respectively). The median age at diagnosis of ovarian IT was 24 years (17-38 years). The median interval from diagnosis of IT to development of GTS was 20 months (8-42 months). These 6 patients underwent 1 to 4 additional surgeries for management of GTS and were alive without evidence of malignancy after a median follow-up of 90 months (range, 24-166 months). CONCLUSIONS: The development of GTS after adjuvant chemotherapy for ovarian IT seems to be more common than previously reported in the literature. Clinicians need to be cognizant that the occurrence of rapidly growing masses during or after chemotherapy for ovarian IT raises the possibility of GTS. This highlights the importance of prolonged follow up with tumor markers and imaging studies in patients with ovarian IT. PMID- 27258730 TI - A Reappraisal of the Incidence of Placental Hydatidiform Mole Using Selective Molecular Genotyping. AB - OBJECTIVE: Reports on the incidence of hydatidiform mole (HM) have varied depending on study population and methodology. This institutional-based study was undertaken to identify the incidence of HM in a modern obstetric practice using advanced laboratory diagnostic techniques. METHODS: A retrospective review of consecutive hospital cases of HM was conducted for a 27-month period. Pathologic diagnoses of partial mole (PM) and complete mole (CM) were based on histopathologic assessment and selective use of p57 immunohistochemistry and molecular genotyping (MG) using formalin-fixed paraffin-embedded tissues. RESULTS: During the study period, 14,944 obstetric deliveries took place at our institution. Forty-nine cases of HM (18 CMs, 31 PMs) were identified. Histopathology with the selective use of p57 immunohistochemistry was used in 25 of 49 HMs (18 CMs, 7 PMs). Histopathologic features were equivocal in the remaining cases (24/49 cases), and adjunctive MG was performed; all were PMs. The incidence of HM was 3.3/1000 deliveries. Partial mole was more prevalent with a CM (PM ratio, 1:1.72). CONCLUSIONS: Our observed incidence of HM is greater than previous studies and is attributable to improved detection of PM cases. Molecular genotyping and cytogenetic evidence indicate that CM is almost half as common as PM. This ratio may be useful in benchmarking laboratory diagnosis and HM registries. PMID- 27258731 TI - Outcome of Neoadjuvant Intra-Arterial Chemotherapy and Radical Hysterectomy for Treatment of Bulky Stage IB to Stage IIB Uterine Cervical Cancer: Can Postoperative Irradiation Be Avoided? AB - OBJECTIVES: We evaluated whether our neoadjuvant intra-arterial chemotherapy (NAIC) effectively precludes the need for postoperative radiation therapy in patients treated by radical hysterectomy for IB2 to IIB cervical cancer. MATERIALS AND METHODS: Study subjects were 52 patients with a bulky cervical tumor diagnosed and treated at Juntendo University Hospital or Juntendo Nerima Hospital. The NAIC combined cisplatin, epirubicin, mitomycin-C, and 5 fluorouracil; and radical hysterectomy was to be performed after 2 cycles. The main variables analyzed were clinical and histologic response to NAIC, NAIC related adverse events, adjuvant chemotherapies, relapse-free and overall survival, recurrence, and prognostic factors. RESULTS: Patients were judged eligible for radical hysterectomy, and 51 underwent the surgery. The overall positive response (complete response [CR] + partial response [PR]) to NAIC was 88.5%. Median follow-up time was 84 months (5-136 months). Three-year relapse free survival and overall survival were 80.5% and 77.8%, respectively. The recurrence rate was 19.2% (10/52 patients). Seven (13.5%) of the 52 patients died from the disease during follow-up. Lymph node status (positive vs negative) and the histologic effect of NAIC (grades 0-1 vs grades 2-3) were shown to be prognostic factors (P = 0.024 and P = 0.021, respectively). CONCLUSIONS: Our NAIC strategy seems to be well tolerated and beneficial for patients with bulky IB2 to IIB cervical cancer. With this strategy, radiation therapy remains an option in cases of recurrence. For cases in which lymph node metastasis is found or the histologic effect of NAIC is low, our adjuvant chemotherapy regimen may need adjustment to improve prognosis. PMID- 27258732 TI - Effect of litter quality on foot pad dermatitis, hock burns and breast blisters in broiler breeders during the production period. AB - Foot pad dermatitis and hock burn lesions are a form of contact dermatitis, a condition affecting skin areas in contact with unsuitable or irritating material. Contact dermatitis is a common problem, reducing the welfare of broilers, and is believed to also affect broiler breeders. However, there is very little research on contact dermatitis in breeders. This study followed the severity of foot pad lesions in broiler breeders throughout the production period. At slaughter the presence of hock burns and breast blisters was also determined. In addition, changes in litter condition over time and the impact of litter quality on foot pads were evaluated. The study was performed on 10 broiler breeder farms, including altogether 18 flocks. Foot pads of 100 hens per flock were assessed at the end of rearing period, three times during the production period, and at slaughter. Foot pad and hock lesions, as well as litter condition were scored on a 5-point scale. Litter quality was evaluated as pH, moisture and ammonia content. The condition of foot pads deteriorated towards slaughter age, with the occurrence of severe lesions reaching a maximum of 64% on average at slaughter. Hock lesions and breast blisters were rare. The litter layer became drier over time. Although poorer litter condition and wetness influenced foot pad health negatively, the effect on severe lesions was not significant. We also observed a negative effect on foot pad condition of larger slat areas. In conclusion, maintaining good litter quality alone is not enough to ensure healthy foot pads in broiler breeders. PMID- 27258733 TI - Impaired inference in a case of developmental amnesia. AB - Amnesia is associated with impairments in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm, we previously showed that age-related impairments in inference were mitigated when judgments could be predicated on known pairwise relations, however, such advantages were not observed in the adult-onset amnesic case D.A. Here, we replicate and extend this finding in a developmental amnesic case (N.C.), who also shows impaired relational learning and transitive expression. Unlike D.A., N.C.'s damage affected the extended hippocampal system and diencephalic structures, and does not extend to neocortical areas that are affected in D.A. Critically, despite their differences in etiology and affected structures, N.C. and D.A. perform similarly on the task. N.C. showed intact pairwise knowledge, suggesting that he is able to use existing semantic information, but this semantic knowledge was insufficient to support transitive expression. The present results suggest a critical role for regions connected to the hippocampus and/or medial prefrontal cortex in inference beyond learning of pairwise relations. (c) 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID- 27258734 TI - Cell adhesion induces overexpression of chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) and contributes to cell adhesion-mediated drug resistance (CAM-DR) in multiple myeloma cells. AB - Previous studies have shown that chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) exerts its anti-apoptotic function in many solid cancers. However, its role in human multiple myeloma (MM) has not been thoroughly elucidated. In this study, we investigate the role of CHD1L in MM. Preliminarily, up-regulation and down-regulation assay verified that CHD1L exerts its anti apoptotic role through the apoptotic pathway involving caspase-9-caspase-3 apoptotic pathway in MM cells. In addition, we determined that CHD1L expression is increased when MM cells were adhered to fibronectin (FN) or bone marrow stromal cell line HS-5 cells and cell adhesion assay indicated that CHD1L siRNA reversed the high cell adhesion rate. Consistent with the reduced adhesion rate, the cells translated to a compromised cell adhesion-mediated drug resistance (CAM DR) phenotype in MM. In summary, we will propose strategies for developing a CHD1L inhibitor for potential treatment of MM. PMID- 27258735 TI - Dysplastic erythroid precursors in the myelodysplastic syndromes and the acute myeloid leukemias: Is there biologic significance? (How should blasts be counted?). AB - The role of bone marrow dysplastic erythroid precursors (EP) in both MDS and AML has been the subject of considerable debate over the past several decades. We have analyzed a large series of adults with MDS and focused on whether any% of EP identified in the bone marrow aspirates of over 1400 patients selected from the Dusseldorf, Germany adult MDS Registry has prognostic relevance. The data was examined for varying% of blasts, the WHO prognostic MDS subtypes and the IPSS-R. We did not identify any adjustment of bone marrow blast percentage by%EP, incuding the 50% rule" developed by the FAB leukemia working group, to have a meaningful impact on outcome, either leukemic risk of progression or overall survival. There was a trend for a%EP<15% to actually have a worse survival than any other EP subset. We can no longer recommend the application of the "50% rule" in the calculation of the% of myeloblasts in bone marrow aspirates. PMID- 27258736 TI - Phototherapy using narrowband ultraviolet B and psoralen plus ultraviolet A is beneficial in steroid-dependent antihistamine-refractory chronic urticaria: a randomized, prospective observer-blinded comparative study. AB - BACKGROUND: Literature on the efficacy of phototherapy in steroid-dependent antihistamine-refractory chronic urticaria (CRU) is limited. OBJECTIVES: To assess and compare the efficacy of psoralen plus ultraviolet A (PUVA) and narrowband ultraviolet B (NB-UVB) in steroid-dependent CRU. METHODS: In this randomized, prospective observer-blinded comparative study, 50 patients with steroid-dependent CRU (6 months of spontaneous urticaria with no response after 3 consecutive months of antihistamines and steroid dependence) were administered either PUVA (group A) or NB-UVB (group B) for 90 days, with a post-treatment follow-up of 90 days. The treatment efficacy was assessed using the average urticaria activity score 7 (aUAS7) and outcome scoring scale (OSS) every 2 weeks. RESULTS: The mean values of aUAS7 progressively decreased from 4.9 +/- 0.8 and 5.0 +/- 0.7 at baseline to 1.9 +/- 0.7 and 1.4 +/- 0.7 in groups A and B, respectively, by day 90. This further decreased to 1.5 +/- 0.8 and 1.4 +/- 1.0 at day 180 in both groups. The values of OSS progressively increased from baseline (1.6 +/- 0.5 in group A and 1.3 +/- 0.5 in group B) to 3.9 +/- 0.3 and 4.0 +/- 0.3 in groups A and B, respectively, by day 90, and 3.9 +/- 0.5 and 4.0 +/- 0.6 by day 180. NB-UVB fared statistically better than PUVA at different time points. Adverse events encountered were minimal and did not warrant treatment discontinuation. CONCLUSIONS: Phototherapy, especially NB-UVB, is an effective, safe and affordable therapeutic modality for steroid-dependent CRU and should be tried prior to third-line treatment options such as omalizumab, ciclosporin and other immunosuppressants. PMID- 27258737 TI - Development of a guinea pig cutaneous radiation injury model using low penetrating X-rays. AB - PURPOSE: A guinea pig skin model was developed to determine the dose-dependent response to soft X-ray radiation into the dermis. MATERIALS AND METHODS: X-ray exposure (50 kVp) was defined to a 4.0 * 4.0 cm area on the lateral surface of a guinea pig using lead shielding. Guinea pigs were exposed to a single fraction of X-ray irradiation ranging from 25-79 Gy via an XRAD320ix Biological Irradiator with the collimator removed. Gross skin changes were measured using clinical assessments defined by the Kumar scale. Skin contracture was assessed, as well as histological evaluations. RESULTS: Loss of dermal integrity was shown after a single dose of soft X-ray radiation at or above 32 Gy with the central 2.0 * 2.0 cm of the exposed site being the most affected. Hallmarks of the skin injury included moist desquamation, ulceration and wound contracture, as well as alterations in epithelium, dermis, muscle and adipose. Changes in the skin were time- and radiation dose-dependent. Full-thickness injury occurred without animal mortality or gross changes in the underlying organs. CONCLUSIONS: The guinea pig is an appropriate small animal model for the short-term screening of countermeasures for cutaneous radiation injury (CRI). PMID- 27258738 TI - Antifungal Imidazole-Decorated Cationic Amphiphiles with Markedly Low Hemolytic Activity. AB - Herein we report that an imidazole-decorated cationic amphiphile derived from the pseudo-disaccharide nebramine has potent antifungal activity against strains of Candida glabrata pathogens. In combination with the natural bis benzylisoquinoline alkaloid tetrandrine the reported antifungal cationic amphiphile demonstrated synergistic antifungal activity against Candida albicans pathogens. This unique membrane disruptor caused no detectible mammalian red blood cell hemolysis at concentrations up to more than two orders of magnitude greater than its minimal inhibitory concentrations against the tested C. glabrata strains. We provide evidence that potency against C. glabrata may be associated with differences between the drug efflux pumps of C. albicans and C. glabrata. Imidazole decorated-cationic amphiphiles show promise for the development of less toxic membrane-disrupting antifungal drugs and drug combinations. PMID- 27258739 TI - Stereoselective PCO/POC-Rearrangement of P-C-Cage Phosphorane in the Reaction of 4,5-Dimethyl-2-(2-oxo-1,2-diphenyl)ethoxy-1,3,2-dioxaphospholane with Hexafluoroacetone. AB - Interaction of 4,5-dimethyl-2-(2-oxo-1,2-diphenyl)ethoxy-1,3,2-dioxaphospholane, bearing a carboxyl group in the gamma-position with respect to the phosphorus atom and obtained from d,l-butanediol, with hexafluoroacetone (CCl4, -40 degrees C) leads to the simultaneous formation of regio- and stereoisomeric cage-like phosphoranes with phosphorus-carbon and phosphorus-oxygen bonds with a high stereoselectivity (>95%), whose structure was determined by 1D and 2D NMR spectroscopy and XRD. When stored as a solution in dichloromethane for one month, the PCO-isomer rearranges into the thermodynamically more stable POC-isomer of the cage-like phosphorane. Mild hydrolysis of the PCO/POC-isomers proceeds with a high chemoselectivity and leads to the formation of P(IV)-dioxaphospholane derivatives. Acidic hydrolysis of the POC-isomer leads to the formation of an oxirane derivative with an unexpectedly high stereoselectivity (>95%). DFT calculations (using the PBE functional) allowed us to obtain structures and energies of the initial phospholane, reaction products (PCO/POC-isomers), and an intermediate P(V)-oxaphosphirane. PMID- 27258759 TI - alphavbeta3- or alpha5beta1-Integrin-Selective Peptidomimetics for Surface Coating. AB - Engineering biomaterials with integrin-binding activity is a very powerful approach to promote cell adhesion, modulate cell behavior, and induce specific biological responses at the surface level. The aim of this Review is to illustrate the evolution of surface-coating molecules in this field: from peptides and proteins with relatively low integrin-binding activity and receptor selectivity to highly active and selective peptidomimetic ligands. In particular, we will bring into focus the difficult challenge of achieving selectivity between the two closely related integrin subtypes alphavbeta3 and alpha5beta1. The functionalization of surfaces with such peptidomimetics opens the way for a new generation of highly specific cell-instructive surfaces to dissect the biological role of integrin subtypes and for application in tissue engineering and regenerative medicine. PMID- 27258760 TI - The Endocrine Society Centennial: Hormones and Apoptosis in the Prostate Gland... Live and Let Die. PMID- 27258761 TI - Programming the Brain from the Womb: Maternal Obesity Perturbs the Hypothalamic Blood-Brain Barrier. PMID- 27258764 TI - Transradial and transulnar access for iliac artery interventions using sheathless guiding systems: A feasibility study. AB - PURPOSE: Our aim was to evaluate the acute success and complication rates of the transradial and transulnar access for iliac artery stenting using sheathless guiding systems. METHODS: Clinical and angiographic data from 156 consecutive patients with symptomatic iliac artery stenosis who were treated with transradial or transulnar access were evaluated. All patients underwent Duplex ultrasound before and after the intervention. The primary endpoints were the procedural success rate, major adverse events, and access site complication rates. The secondary endpoints were the angiographic result of the iliac artery intervention, fluoroscopy time, X-ray dose, procedure length, crossover rate to another puncture site and hospitalization duration. The impact of the learning curve was also investigated, along with right or left radial access. RESULTS: The indication for the intervention was intermittent claudication in 109 patients (69.9%), critical limb ischemia in 44 (28.2%) subjects and acute limb ischemia in three individuals (1.9%). Technical success was achieved in 155 patients (99.4%), with a crossover rate of 3.8%. Radial and ulnar artery access was used in 151 (96.8%) and 7 (4.5%) patients, respectively. The Ankle-brachial index increased from 0.69 [0.65-0.72] to 0.91 [0.88-0.95] as a result of the procedures (P < 0.001). The cumulative incidence of major adverse events was 3.8% at the 2-month follow-up (0% in patients with intermittent claudication and 13.8% in patients with critical limb ischemia). Radial artery access site complications were encountered in eight patients (5.1%). We documented decreased X-ray doses (1742.0 [783.9-2701] vs. 1435 [991.1-1879] vs. 692.8 [275.3-1110] Gy cm-2 P < 0.05) over time; however, the fluoroscopy time, procedure time, and contrast consumption were not significantly different. Left hand access was not associated with significantly better results than right radial artery access. CONCLUSIONS: Iliac artery stenting can be safely and effectively performed using radial or ulnar artery access and sheathless guiding catheters, with acceptable complication rates and high levels of technical success. The physician learning curve plays an important role in decreasing the X-ray dose. (c) 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc. PMID- 27258766 TI - Reconstruction of the Internal Carotid Artery After Treatment of Complex Traumatic Direct Carotid-Cavernous Fistulas With the Willis Covered Stent: A Retrospective Study With Long-Term Follow-up. AB - BACKGROUND: Endovascular treatment of complex traumatic direct carotid-cavernous fistulas (TDCCFs) is a challenge. OBJECTIVE: To evaluate the long-term efficacy of the Willis covered stent in endovascular treatment of complex TDCCFs, focusing on reconstruction and preservation of the internal carotid artery. METHODS: During the past 8 years, 25 patients with 27 TDCCFs who previously had unsuccessful treatment of fistulas with detachable balloons received endovascular treatment with Willis covered stents. The efficacy, complications, in-stent stenosis, angiographic, and clinical follow-up results were evaluated retrospectively between 6 and 88 months (mean, 43.8 months) after the stent placement. RESULTS: The technical success rate of stenting placement was 100%. Forty-four Willis covered stents were implanted into the target artery of 27 TDCCFs. Complete exclusion was achieved in 16 patients with 17 TDCCFs immediately after the stent placement, with transient endoleaks in 10 TDCCFs. Redilation was performed in 6 TDCCFs, and additional stents were implanted in the other 4 TDCCFs for endoleak exclusion. The initial angiographic results showed complete exclusion of fistulas with preservation of the internal carotid artery in 24 patients with 26 TDCCFs. One patient in whom complete occlusion initially was achieved subsequently experienced a delayed endoleak, which required placement of an additional stent. The angiographic follow-up results (mean, 30.3 months) demonstrated complete exclusion in all 27 TDCCFs, with patency of internal carotid artery in 23 patients. The clinical follow-up demonstrated a full recovery in 23 patients and improvement in 2 patients. CONCLUSION: The use of Willis covered stents was confirmed to be effective, safe, and a curative approach for endovascular treatment of complex TDCCFs and internal carotid artery reconstruction. ABBREVIATIONS: DB, detachable balloonEVT, endovascular treatmentICA, internal carotid arteryn-BCA, N-butyl cyanoacrylateTDCCF, traumatic direct carotid-cavernous fistula. PMID- 27258768 TI - Surgical Resection and Interstitial Iodine-125 Brachytherapy for High-Grade Meningiomas: A 25-Year Series. AB - BACKGROUND: Atypical and malignant meningiomas can recur despite resection and radiation. OBJECTIVE: To determine outcomes of patients with recurrent atypical or malignant meningioma treated with repeat resection and permanent iodine-125 ( 125 I) brachy-therapy. METHODS: Charts of patients who underwent surgical resection and 125 I brachyther-apy implantation for atypical and malignant meningiomas between 1988 and 2013 were retrospectively reviewed. The Kaplan-Meier actuarial method was used to calculate progression-free and overall survival. The log-rank test was used to compare groups. Significance was set at P < .05. RESULTS: Forty-two patients underwent 50 resections with 125 I brachytherapy im plantations. All patients had undergone previous resections and 85% had previously undergone radiation. Median follow-up was 7.5 years after diagnosis and 2.3 years after brachytherapy. Median time to progression after resection with 125 I brachytherapy was 20.9 months for atypical meningioma, 11.4 months for malignant meningioma, and 11.4 months for the combined groups. Median survival after re-resection and 125 I brachytherapy was 3.5 years for atypical meningioma, 2.3 years for malignant menin-gioma, and 3.3 years for all subjects. Median overall survival after diagnosis was 11.1 years for atypical meningioma, 9.1 years for malignant meningioma, and 9.4 years for all subjects. Complications occurred in 17 patients and included radiation necrosis (n = 8, 16%), wound breakdown (n = 6, 12%), hydrocephalus (n = 4, 8%), infection (n = 3, 6%), and a pseudomeningocele (n = 2, 5%). CONCLUSION: This is the largest experience with adjuvant 125 I brachytherapy for recurrent high-grade meningiomas. The outcomes support the use of adjuvant brachytherapy as an option for these aggressive tumors. PMID- 27258769 TI - Quality of Postoperative Venous Thromboembolism Prophylaxis in Neuro-oncologic Surgery. AB - BACKGROUND: Given the vagaries of published guidelines and the lack of high quality evidence on the method, timing, and dose of venous thromboembolism (VTE) prophylaxis in neurological surgery, little is known about practice patterns regarding VTE prophylaxis in the United States. OBJECTIVE: To estimate the use of VTE prophylaxis in patients who underwent surgery for a cerebral neoplasm and to identify patient, physician, and hospital characteristics associated with prophylaxis. METHODS: Using the Premier Perspective database, we classified patients undergoing surgery for intracranial neoplasm between 2006 and 2012 on the basis of the type of VTE prophylaxis they received (mechanical, pharmacological, or combination). Generalized estimating equations were used to analyze the effects of pretreatment patient and system variables, including hospital and surgeon volume, on prophylaxis while controlling for hospital clustering. RESULTS: A total of 43 327 patients were identified. Venous thromboembolism prophylaxis was given to 70.2% of patients. Overall, 16 957 (39.2%) had only mechanical prophylaxis, 5628 (13%) received only pharmacological prophylaxis, and 7826 (18.1%) received combination prophylaxis. Patients with high-volume providers (odds ratio, 2.22; 95% confidence interval, 1.33-3.69) were more likely to receive prophylaxis. CONCLUSION: Nearly one-third of patients who underwent surgery for an intracranial tumor did not receive any VTE prophylaxis. We noted that the rate of overall VTE prophylaxis did not significantly change over the course of the 7 years analyzed despite an increasing focus on complication prevention. High-volume surgeons were more likely to provide VTE prophylaxis. PMID- 27258770 TI - Anticonvulsant discovery through animal models of status epilepticus induced by organophosphorus nerve agents and pesticides. AB - Organophosphorus pesticides (OPs) and nerve agents (NAs) are highly toxic chemicals that pose a significant threat to human health worldwide. These compounds induce status epilepticus (SE) by irreversibly blocking the ability of acetylcholinesterase to break down acetylcholine at neural synapses. Animal models of organophosphate-induced SE are a crucial resource for identifying new anticonvulsant therapies. Here, we describe the development of various animal models of SE induced by NA or OP exposure. Experiments in nonhuman primates, rats, mice, and guinea pigs have helped to identify novel therapeutic targets in the central nervous system, with particular success at modulating GABAergic and glutamatergic receptors. The anticonvulsants identified by NA- and OP-induced SE models are well poised for fast advancement into clinical development, and their potential utility in the broader field of epilepsy should make them all the more attractive for commercial pursuit. PMID- 27258771 TI - Simultaneous Bilateral Ophthalmic Artery Chemosurgery for Bilateral Retinoblastoma (Tandem Therapy). AB - OBJECTIVE: Report on the 7-year experience with bilateral ophthalmic artery chemosurgery (OAC-Tandem therapy) for bilateral retinoblastoma. DESIGN: Retrospective, single institution study. SUBJECTS: 120 eyes of 60 children with bilateral retinoblastoma treated since March 2008. METHODS: Retrospective review of all children treated at Memorial Sloan Kettering with bilateral ophthalmic artery chemosurgery (Melphalan, Carboplatin, Topotecan, Methotrexate) delivered in the same initial session to both naive and previously treated eyes. MAIN OUTCOME MEASURES: Ocular survival, metastatic disease, patient survival from metastases, second cancers, systemic adverse effects, need for transfusion of blood products, electroretinogram before and after treatment. RESULTS: 116 eyes were salvaged (4 eyes were enucleated: 3 because of progressive disease, 1 family choice). Kaplan Meier ocular survival was 99.2% at one year, 96.9% at 2 and 3 years and 94.9% for years 4 through 7. There were no cases of metastatic disease or metastatic deaths with a mean follow-up of 3.01 years. Two children developed second cancers (both pineoblastoma) and one of them died. Transfusion of blood products was required in 3 cases (4 transfusions), 1.9%. Two children developed fever/neutropenia requiring hospitalization (0.95%). ERGs were improved in 21.6% and unchanged after treatment in 52.5% of cases (increase or decrease of less than 25MUV). CONCLUSIONS: Bilateral ophthalmic artery chemosurgery is a safe and effective technique for managing bilateral retinoblastoma-even when eyes are advanced bilaterally, and if both eyes have progressed after systemic chemotherapy. Ocular survival was excellent (94.9% at 8 years), there were no cases of of metastatic disease and no deaths from metastatic disease, but children remain at risk for second cancers. In 21.6% of cases ERG function improved. Despite using chemotherapy in both eyes in the same session, systemic toxicity was low. PMID- 27258773 TI - Toward an Earlier Diagnosis of Primary Ciliary Dyskinesia. Which Patients Should Undergo Detailed Diagnostic Testing? AB - Primary ciliary dyskinesia (PCD) is a rare, heterogeneous, recessive, genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms. Prevalence is estimated at around 1:10,000, but many patients remain undiagnosed, whereas others receive the label incorrectly. Proper diagnosis is complicated by the fact that the key symptoms, such as wet cough, chronic rhinitis, and recurrent upper and lower respiratory infection, are common and nonspecific. There is no single gold standard test to diagnose PCD. Currently, the diagnosis is made in patients with a compatible medical history after a demanding combination of tests including nasal nitric oxide, high-speed video microscopy, and transmission electron microscopy and genetic and ciliary culture testing. These tests are costly and need sophisticated equipment and experienced staff, restricting use to highly specialized centers. Therefore, it would be desirable to have a screening test for identifying those patients who should undergo detailed diagnostic testing. Three recent studies focused on potential screening tools: one study assessed the validity of nasal nitric oxide for screening, and two studies developed new symptom-based screening tools. These simple tools are welcome, and it is hoped that they will assist physicians in determining whom to refer for definitive testing. However, they have been developed in tertiary care settings, where 10 to 50% of tested patients have PCD. The sensitivity and specificity of the tools are reasonable, but positive and negative predictive values may be poor in primary or secondary care settings. Although these studies are an important step toward an earlier diagnosis of PCD, more remains to be done before we have tools tailored to different health care settings. PMID- 27258772 TI - Structure of the Plexin Ectodomain Bound by Semaphorin-Mimicking Antibodies. AB - Semaphorin family proteins act on cells to mediate both repulsive and attractive guidance via binding to plexin family receptors, thereby playing fundamental roles in the morphogenesis and homeostasis of various tissues. Although semaphorin-plexin signaling is implicated in various diseases and is thus a target of intensive research, our mechanistic understanding of how semaphorins activate plexins on the cell surface is limited. Here, we describe unique anti plexin-A1 antibodies that can induce a collapsed morphology in mouse dendritic cells as efficiently as the semaphorin 3A (Sema3A) ligand. Precise epitope analysis indicates that these "semaphorin-mimicking" antibodies dimerize cell surface plexin-A1 by binding to the N-terminal sema domain of the plexin at sites away from the interface used by the Sema3A ligand. Structural analysis of plexin A1 fragments using negative stain electron microscopy further revealed that this agonistic capacity is closely linked to the location and orientation of antibody binding. In addition, the full-length plexin-A1 ectodomain exhibited a highly curved "C" shape, reinforcing the very unusual dimeric receptor conformation of this protein at the cell surface when engaged with Sema3A or agonistic antibodies. PMID- 27258774 TI - Protein a Immunoadsorption May Hamper the Decision to Transplant Due to Interference With CDC Crossmatch Results. AB - Transplanting immunized patients requires immunological monitoring in the pretransplant phase to follow reduction of donor specific HLA antibodies (DSA) after Staphylococcus aureus protein A (SPA) immunoadsorption (IA) or therapeutic plasma exchange followed by IVIG and Rituximab administration. Pretreatment aims to significantly reduce DSA strength. The Tissue Typing Lab at Aarhus University Hospital performs immunological monitoring of approximately 150 kidney transplantation patients per year from two transplant centers. From 2012 to 2013, we experienced seven patients desensitized using SPA IA, initially presenting negative cytotoxic complement dependent (CDC) T-cell crossmatches but positive B and T cell flowcytometric crossmatch, who despite significant DSA reduction developed weakly positive CDC T-cell crossmatch shortly prior to transplantation. We hypothesised that leached SPA during IA could be the cause, as the complication was not observed in patients who received plasma exchanges. We found that the positive CDC was not donor specific and SPA column material incubated with control serum reproduced a positive CDC T-cell crossmatch. Finally, we detected leached SPA in one of the patient samples using a highly sensitive time resolved fluorescent assay. In conclusion, the results emphasize the importance of carefully considering CDC crossmatch results subsequent to IA, before a planned transplantation is either postponed or cancelled. J. Clin. Apheresis 32:163-169, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27258775 TI - Update on childhood craniopharyngiomas. AB - PURPOSE OF REVIEW: Craniopharyngioma location impacts treatment approach. Imaging advances allow for better anatomical localization, which can help determine the best surgical plan. Recent discoveries have also led to a better understanding of craniopharyngioma development and potential treatments. This review includes publications January 2015 through March 2016 and prior key reports. RECENT FINDINGS: Recent findings confirm that third ventricular and hypothalamic involvement are associated with highest risk of hypothalamic dysfunction after surgery. Both presentation and MRI can aid in presurgical grading to try to limit development of hypothalamic obesity, somnolence, neurocognitive dysfunction, decreased quality of life, and other morbidities. Targeted therapies may also prove useful in avoiding treatment complications. In total, 14-50% of adult-onset craniopharyngioma are papillary; the majority with a mutation in exon 3 of BRAF and may respond to BRAF inhibitors and mitogen-activated protein kinase inhibitors. The remaining adult-onset and majority of childhood-onset are adamantinomatous; often with mutations in CTNNB1, which encodes beta-catenin, leading to overactivation of the WNT signaling pathway. SUMMARY: Significant morbidities are associated with craniopharyngioma. Targeted medical therapies are on the horizon. Until that time, the surgical approach and decision for radiation therapy should be chosen to limit long-term sequelae. PMID- 27258776 TI - The Conformational Map of Volatile Anesthetics: Enflurane Revisited. AB - Previous ambiguities in the conformational and structural landscape of the volatile anesthetic enflurane have been solved combining microwave spectroscopy in a jet expansion and ab initio calculations. The broadband (2-18 GHz) rotational spectra identified three different rotamers, sharing a common trans ether skeleton but differing in the +/-gauche/trans position of the terminal chlorine atom. For each chlorine conformation two different gauche orientations were predicted for the opposite difluoromethyl group, but only one is experimentally observable due to collisional relaxation in the jet. The experimental dataset comprised nine different isotopologues ((35) Cl, (37) Cl, (13) C) and a large number (>6500) of rotational transitions. The inertial data provided structural information using the substitution and effective procedures. The structural preferences were rationalized with additional ab initio, natural bond-orbital and non-covalent-interaction analysis, which suggest that plausible anomeric effects at the difluoromethyl group could be overridden by other intramolecular effects. The difluoromethyl orientation thus reflects a minimization of inter-fluorine repulsions while maximizing F???H attractive interactions. A comparison with previous electron diffraction and spectroscopic data in the gas and condensed phases finally resulted in a comprehensive description of this ether, completing a rotational description of the most common multi-halogenated anesthetics. PMID- 27258780 TI - The historical context in conversation: Lexical differentiation and memory for the discourse history. AB - When designing a definite referring expression, speakers take into account both the local context and certain aspects of the historical context, including whether similar referents have been mentioned in the past. When a similar item has been mentioned previously, speakers tend to elaborate their referring expression in order to differentiate the two items, a phenomenon called lexical differentiation. The present research examines the locus of the lexical differentiation effect and its relationship with memory for the discourse. In three experiments, we demonstrate that speakers differentiate to distinguish current from past referents; there was no evidence that speakers differentiate in order to avoid giving two items the same label. Post-task memory tests also revealed a high level of memory for the discourse history, a finding that is inconsistent with the view that failures of memory underlie low differentiation rates. Instead, memory for the discourse history, while necessary, is not sufficient for speakers to design language with respect to the historical context. Speakers must additionally view the discourse history as relevant to design language with respect to this broader context. Finally, measures of memory for past referents point to asymmetries between speakers and listeners in their memory for the discourse, with speakers typically remembering the discourse history better. PMID- 27258781 TI - Improving the Efficiency and Activity of Electrocatalysts for the Reduction of CO2 through Supramolecular Assembly with Amino Acid-Modified Ligands. AB - The use of hydrogen-bonding interactions to direct the noncovalent assembly of a Re-based bimetallic supramolecular electrocatalyst containing either tyrosine or phenylalanine residues is reported. Computational modeling and spectroelectrochemical characterization indicate that under catalytic conditions the phenol residues of tyrosine can act both as pendant proton sources and participate in the structural assembly of the bimetallic active species. As a result, an increased rate of catalysis is observed experimentally for the reductive disproportionation of CO2 to CO and CO3(2-) by a tyrosine-modified complex in comparison to a control complex containing phenylalanine residues. These findings demonstrate that noncovalent assembly is a powerful method for generating new bimetallic electrocatalyst systems where the choice of substituent can be used to both control structural assembly and introduce cocatalytic moieties. PMID- 27258782 TI - Progress and clinical potential of antibody-targeted therapy for arthritic damage. AB - INTRODUCTION: The advent of biologic drugs like infliximab, Etanercept, rituximab and tocilizumab has greatly improved the treatment of rheumatoid arthritis, however, increased risk of infection and high cost still remain unmet needs. A new generation of targeted therapeutics is being developed to target payload drug specifically to arthritic tissue; to concentrate the drug in the disease area and limit the off target systemic exposure. This might also reduce total effective dose. AREAS COVERED: This article summarizes the properties and progress of targeted therapies that have been published on PubMed, and addresses their clinical potential. Expert commentary: Incredible progress with targeted therapies has already been made in the short time since the principle was first proven in animal models in 2007 when targeting payload drug to overexpressed oncofetal domain of fibronectin in inflamed arthritic joints. PMID- 27258783 TI - Tyrosine-phosphorylation of the scaffold protein ADAP and its role in T cell signaling. AB - INTRODUCTION: The Adhesion and Degranulation promoting Adaptor Protein (ADAP) is phosphorylated upon T cell activation and acts as a scaffold for the formation of a signaling complex that integrates molecular interactions between T cell or chemokine receptors, the actin cytoskeleton, and integrin-mediated cellular adhesion and migration. AREAS COVERED: This article reviews current knowledge of the functions of the adapter protein ADAP in T cell signaling with a focus on the role of individual phosphotyrosine (pY) motifs for SH2 domain mediated interactions. The data presented was obtained from literature searches (PubMed) as well as the authors own research on the topic. Expert commentary: ADAP can be regarded as a paradigmatic example of how tyrosine phosphorylation sites serve as dynamic interaction hubs. Molecular crowding at unstructured and redundant sites (pY595, pY651) is contrasted by more specific interactions enabled by the three dimensional environment of a particular phosphotyrosine motif (pY571). PMID- 27258784 TI - Stereoselective Synthesis of the C9-C19 Fragment of Peloruside A. AB - A concise synthesis of the C9-C19 fragment of peloruside A that is both highly stereoselective and efficient is described. Achieving an overall yield of 23% over 14 steps, this synthesis not only is high yielding but also involves four chromatography steps. This approach is based on the addition of metal enolates of chiral auxiliary scaffolds generated by either catalytic or stoichiometric amounts of nickel(II) or titanium(IV) Lewis acids. PMID- 27258785 TI - The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873. AB - Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation. However, it is not yet clear whether lncRNAs can regulate necrosis in cardiomyocytes. Here, we report that a long noncoding RNA, named necrosis-related factor (NRF), regulates cardiomyocytes necrosis by targeting miR-873 and RIPK1 (receptor interacting serine/threonine-protein kinase 1)/RIPK3 (receptor-interacting serine/threonine-protein kinase 3). Our results show that RIPK1 and RIPK3 participate in H2O2-induced cardiomyocytes necrosis. miR-873 suppresses the translation of RIPK1/RIPK3 and inhibits RIPK1/RIPK3-mediated necrotic cell death in cardiomyocytes. miR-873 reduces myocardial infarct size upon ischemia/reperfusion (I/R) injury in the animal model. In exploring the molecular mechanism by which miR-873 expression is regulated, we identify NRF as an endogenous sponge RNA and repress miR-873 expression. NRF directly binds to miR 873 and regulates RIPK1/RIPK3 expression and necrosis. Knockdown of NRF antagonizes necrosis in cardiomyocytes and reduces necrosis and myocardial infarction upon I/R injury. Further, we identify that p53 transcriptionally activates NRF expression. P53 regulates cardiomyocytes necrosis and myocardial I/R injury through NRF and miR-873.Our results identify a novel mechanism involving NRF and miR-873 in regulating programmed necrosis in the heart and suggest a potential therapeutic avenue for cardiovascular diseases. PMID- 27258786 TI - K45A mutation of RIPK1 results in poor necroptosis and cytokine signaling in macrophages, which impacts inflammatory responses in vivo. AB - Receptor interacting protein kinase 1 (RIPK1) participates in several cell signaling complexes that promote cell activation and cell death. Stimulation of RIPK1 in the absence of caspase signaling induces regulated necrosis (necroptosis), which promotes an inflammatory response. Understanding of the mechanisms through which RIPK1 promotes inflammation has been unclear. Herein we have evaluated the impact of a K45A mutation of RIPK1 on necroptosis of macrophages and the activation of inflammatory response. We show that K45A mutation of RIPK1 results in attenuated necroptosis of macrophages in response to stimulation with LPS, TNFalpha and IFNbeta in the absence of caspase signaling. Impairment in necroptosis correlated with poor phosphorylation of RIPK1, RIPK3 and reduced trimerization of MLKL. Furthermore, K45A mutation of RIPK1 resulted in poor STAT1 phosphorylation (at S727) and expression of RANTES and MIP-1alpha following TNF-R engagement in the absence of caspase activation. Our results further indicate that in the absence of stimulation by pathogen-associated molecular patterns (PAMPs), cellular inhibitors of apoptotic proteins (cIAPs) prevent the K45-dependent auto-phosphorylation of RIPK1, leading to resistance against necroptosis. Finally, RIPK1(K45A) mice displayed attenuated inflammatory response in vivo as they were significantly resistant against endotoxin shock, but highly susceptible against a challenge with Salmonella typhimurium. This correlated with reduced expression of IL-1beta and ROS, and poor processing of caspase 8 by RIPK1(K45A) macrophages. Overall, these results indicate that K45 mediated kinase activity of RIPK1 is not only important for necroptosis but it also has a key role in promoting cytokine signaling and host response to inflammatory stimuli. PMID- 27258788 TI - Infectious Angiogenesis-Different Pathways, the Same Goal. AB - Infectious angiogenesis is the biological response of neoangiogenesis induced by infectious organisms. The authors present 3 exemplary entities which show paradigmatic clinico-pathological settings of infectious angiogenesis: Bacillary angiomatosis, Orf (ecthyma contagiosum), and Kaposi sarcoma. The authors review the literature and elucidate etiopathogenetic pathways leading to the phenomenon of neovascularization stimulated by infectious organisms. The authors describe the clinical and histological pictures, interactions between microorganisms and host cells, and changes that occur within cellular structures, as well as angiogenic factors that underpin infectious angiogenesis. The importance of chronic inflammation and tumor angiogenesis is emphasized. PMID- 27258787 TI - Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth. AB - Mutations in the p53 tumor-suppressor gene are prevalent in human cancers. The majority of p53 mutations are missense, which can be classified into contact mutations (that directly disrupts the DNA-binding activity of p53) and structural mutations (that disrupts the conformation of p53). Both of the mutations can disable the normal wild-type (WT) p53 activities. Nevertheless, it has been amply documented that small molecules can rescue activity from mutant p53 by restoring WT tumor-suppressive functions. These compounds hold promise for cancer therapy and have now entered clinical trials. In this study, we show that cruciferous vegetable-derived phenethyl isothiocyanate (PEITC) can reactivate p53 mutant under in vitro and in vivo conditions, revealing a new mechanism of action for a dietary-related compound. PEITC exhibits growth-inhibitory activity in cells expressing p53 mutants with preferential activity toward p53(R175), one of the most frequent 'hotspot' mutations within the p53 sequence. Mechanistic studies revealed that PEITC induces apoptosis in a p53(R175) mutant-dependent manner by restoring p53 WT conformation and transactivation functions. Accordingly, in PEITC-treated cells the reactivated p53(R175) mutant induces apoptosis by activating canonical WT p53 targets, inducing a delay in S and G2/M phase, and by phosphorylating ATM/CHK2. Interestingly, the growth-inhibitory effects of PEITC depend on the redox state of the cell. Further, PEITC treatments render the p53(R175) mutant sensitive to degradation by the proteasome and autophagy in a concentration-dependent manner. PEITC-induced reactivation of p53(R175) and its subsequent sensitivity to the degradation pathways likely contribute to its anticancer activities. We further show that dietary supplementation of PEITC is able to reactivate WT activity in vivo as well, inhibiting tumor growth in xenograft mouse model. These findings provide the first example of mutant p53 reactivation by a dietary compound and have important implications for cancer prevention and therapy. PMID- 27258789 TI - Survival and Metabolic Activity of Listeria monocytogenes on Ready-to-Eat Roast Beef Stored at 4 degrees C. AB - Three brands of commercial roast beef were purchased and artificially inoculated with a 5-strain Listeria monocytogenes cocktail at 2 inoculation levels (approximately 3 and 6 Log CFU/g). Although all 3 brands contained sodium diacetate and sodium lactate, inoculated Listeria cocktail survived for 16 d in all 3 brands; significant increases in L. monocytogenes numbers were seen on inoculated Brand B roast beef on days 12 and 16. Numbers of L. monocytogenes increased to 4.14 Log CFU/g for the 3 Log CFU/g inoculation level and increased to 7.99 Log CFU/g for the 6 Log CFU/g inoculation level by day 16, with the pH values being 5.4 and 5.8 respectively. To measure the cell viability in potential biofilms formed, an Alamar blue assay was conducted. Brand B meat homogenate had the highest metabolic activities (P < 0.05). By comparing its metabolic activities to Brands A and C and the inoculated autoclaved meat homogenates, results indicated that the microflora present in Brand B may be the reason for high metabolic activities. Based on the denaturing gradient gel electrophoresis and the Shannon-Wiener diversity index analysis, the "Brand" factor significantly impacted the diversity index (P = 0.012) and Brand B had the highest microflora diversity (Shannon index 1.636 +/- 0.011). Based on this study, results showed that antimicrobials cannot completely inhibit the growth of L. monocytogenes in ready-to-eat roast beef. Native microflora (both diversity and abundance), together with product formula, pH, antimicrobial concentrations, and storage conditions may all impact the survival and growth of L. monocytogenes. PMID- 27258790 TI - Structure Characterization and Properties of K-Containing Copper Hexacyanoferrate. AB - Copper hexacyanoferrate, Cu(II)[Fe(III)(CN)6]2/3.nH2O, was synthesized, and varied amounts of K(+) ions were inserted via reduction by K2S2O3 (aq). Ideally, the reaction can be written as Cu(II)[Fe(III)(CN)6]2/3.nH2O + 2x/3K(+) + 2x/3e(-) <-> K2x/3Cu(II)[Fe(II)xFe(III)1-x(CN)6]2/3.nH2O. Infrared, Raman, and Mossbauer spectroscopy studies show that Fe(III) is continuously reduced to Fe(II) with increasing x, accompanied by a decrease of the a-axis of the cubic Fm3m unit cell. Elemental analysis of K by inductively coupled plasma shows that the insertion only begins when a significant fraction, ~20% of the Fe(III), has already been reduced. Thermogravimetric analysis shows a fast exchange of water with ambient atmosphere and a total weight loss of ~26 wt % upon heating to 180 degrees C, above which the structure starts to decompose. The crystal structures of Cu(II)[Fe(III)(CN)6]2/3.nH2O and K2/3Cu[Fe(CN)6]2/3.nH2O were refined using synchrotron X-ray powder diffraction data. In both, one-third of the Fe(CN)6 groups are vacant, and the octahedron around Cu(II) is completed by water molecules. In the two structures, difference Fourier maps reveal three additional zeolitic water sites (8c, 32f, and 48g) in the center of the cavities formed by the -Cu-N-C-Fe- framework. The K-containing compound shows an increased electron density at two of these sites (32f and 48g), indicating them to be the preferred positions for the K(+) ions. PMID- 27258791 TI - Water-Regulated Self-Assembly Structure Transformation and Gelation Behavior Prediction Based on a Hydrazide Derivative. AB - Herein, we report the water-regulated supramolecular self-assembly structure transformation and the predictability of the gelation ability based on an azobenzene derivative bearing a hydrazide group, namely, N-(3,4,5 tributoxyphenyl)-N'-4-[(4-hydroxyphenyl)azophenyl] benzohydrazide (BNB-t4). The regulation effects are demonstrated in the morphological transformation from spherical to lamellar particles then back to spherical in different solvent ratios of n-propanol/water. The self-assembly behavior of BNB-t4 was characterized by minimum gelation concentration, microstructure, thermal, and mechanical stabilities. From the spectroscopy studies, it is suggested that gel formation of BNB-t4 is mainly driven by intermolecular hydrogen bonding, accompanied with the contribution from pi-pi stacking as well as hydrophobic interactions. The successfully established correlation between the self-assembly behavior and solubility parameters yields a facile way to predict the gelation performance of other molecules in other single or mixed solvents. PMID- 27258792 TI - The Impact of Implementation of Family-Initiated Escalation of Care for the Deteriorating Patient in Hospital: A Systematic Review. AB - BACKGROUND: Rapid response systems incorporate concepts of early recognition of patient deterioration, prompt reporting, and response which result in escalation of patient care. The ability to initiate escalation of care is now being extended to families of hospitalized patients. RESEARCH AIMS: To identify the impact of implementation of family-initiated escalation of care for the deteriorating patient in hospital? METHODS: A systematic review of peer-reviewed publications was conducted. Databases were searched from January 2005 to May 2015 for articles reporting the implementation and evaluation of family involvement programs. Reference lists of retrieved articles were searched. RESULTS: Ten articles (all descriptive studies) reported implementation and evaluation of response systems for patients and families to trigger an alert for help; five described a triaged response; five reported systems for families to directly activate the rapid response team. Five articles reported implementation in the pediatric setting. There were a total of 426 family-initiated calls, range 0.17 to 11 per month, with no deaths reported. All calls were deemed to be appropriate and three calls resulted in intensive care unit admissions. The basis of patient- or family initiated calls stemmed from communication or systems breakdown. The large range in frequency of calls was associated with the process implemented, the strategies used and the calling criteria (up to four). Feedback from families was positive. There appeared to be a level of staff stress associated with introducing this process. LINKING EVIDENCE TO ACTION: A variety of practice models and calling criteria were reported to either directly activate an existing rapid response team or trigger a separate response to patient- or family-initiated calls. The broader calling criteria and more comprehensive implementation strategies were associated with more patient- and family-initiated escalation of care calls. There is no systematically researched evidence to assess the value of family initiated calls for deteriorating patients. PMID- 27258793 TI - Brianyoungite/Graphene Oxide Coordination Composites for High-Performance Cu(2+) Adsorption and Tunable Deep-Red Photoluminescence. AB - Graphene oxide (GO) is a good adsorbent for heavy-metal ions because the oxygen functional groups offer active adsorption sites, but a small-size GO with dense oxygen-containing groups has high water solubility causing difficulty in separation. Herein, GO is bound to large brianyoungite (BY) by Zn-O coordination via a hydrothermal reaction that produces BY-GO composites with hollow spherical and flakelike morphologies that are easy to remove. By producing abundant oxygen containing groups on GO, the Cu(2+) adsorption capacity increases to 1724.1 mg/g, which is the highest value in graphene-related materials. The experimental and theoretical analysis clearly shows that the infrared spectral shifts toward the low-frequency side of C-O-H and O?C-O bending vibrations in the BY-GO composites stem from the Zn(2+) (or Cu(2+)) coordination with O atoms in GO. The BY-GO also exhibits tunable deep-red photoluminescence up to 750 nm with a quantum yield of about 1%, which may be useful in infrared optoelectronic devices and solar energy exploitation. The photoluminescence which is different from that previously reported from chemically derived GO can be attributed to the optical transition in the disorder-induced localized states of the carbon-oxygen functional groups. PMID- 27258795 TI - Coinheritance of a Rare Nucleotide Substitution on the beta-Globin Gene and Other Known Mutations in the Globin Clusters: Management in Genetic Counseling. AB - A large number of methods for DNA analysis are available to identify defects in globin genes associated with hemoglobin (Hb) disorders. In this study, we report a rare nucleotide (nt) substitution on the beta-globin gene, nt 781 in the second intron [IVS-II-781 (C > G); HBB: c.316-70C > G], identified in four patients. This nt substitution was previously described only as a personal communication to the HbVar database and indicated as a beta(0) or beta(+) mutation. The purpose of this study was to evaluate the clinical implication of this nt change, particularly when coinherited with severe beta-thalassemia (beta-thal), in order to be able to conduct appropriate genetic counseling. Genetic studies were performed on two subjects, one carried Hb S [beta6(A3)Glu->Val; HBB: c.20A > T], and the other carried IVS-I-110 (G > A) (HBB: c.93-21G > A). All these subjects showed this new beta nt substitution in association with Hb A2' (or Hb B2) [delta16(A13)Gly->Arg; HBD: c.49G > C]. Another 16 samples, carrying the same delta variant as the probands, were processed by beta-globin gene sequencing in order to better understand the correlation between this Hb variant and the rare nt substitution reported in this study. The present investigation emphasizes the importance of sharing the observed nt changes in the globin gene cluster, especially in the case of new or rare undefined mutations, in order to facilitate the determination of their phenotypic expression, the possible interactions with known molecular defects and to formulate appropriate genetic counseling for at risk couples. PMID- 27258796 TI - Female Urology - Quo Vadis? PMID- 27258794 TI - Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification. AB - Activation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) and class-switch recombination (CSR) by deaminating C->U during transcription of Ig-variable (V) and Ig-switch (S) region DNA, which is essential to produce high-affinity antibodies. Here we report the crystal structure of a soluble human AID variant at 2.8A resolution that favors targeting WRC motifs (W=A/T, R=A/G) in vitro, and executes Ig V SHM in Ramos B-cells. A specificity loop extending away from the active site to accommodate two purine bases next to C, differs significantly in sequence, length, and conformation from APOBEC proteins Apo3A and Apo3G, which strongly favor pyrimidines at -1 and -2 positions. Individual amino acid contributions to specificity and processivity were measured in relation to a proposed ssDNA binding cleft. This study provides a structural basis for residue contributions to DNA scanning properties unique to AID, and for disease mutations in human HIGM-2 syndrome. PMID- 27258798 TI - Treatment of bacterial vaginosis in pregnancy in order to reduce the risk of spontaneous preterm delivery - a clinical recommendation. AB - INTRODUCTION: Bacterial vaginosis (BV) is characterized by a dysbiosis of the vaginal microbiota with a depletion of Lactobacillus spp. In pregnancy, prevalence's between 7 and 30% have been reported depending on the study population and the definition. BV may be associated with an increased risk of spontaneous preterm delivery (sPTD). However, it is controversial whether or not BV-positive pregnant women will benefit from treatment to reduce the risk of sPTD. We could not identify any good-quality guideline addressing this issue. Consequently we aimed to produce this clinical recommendation based on GRADE. MATERIAL AND METHODS: Systematic literature searches were conducted in the following databases: Guidelines International Network: G-I-N, Medline, Embase, The Cochrane Database of Systematic Reviews, Web of Science and http://www.clinicaltrials.gov from 1999 to 3 October 2014. Hence, nine guidelines, 34 reviews, 18 randomized controlled trials and 12 observational studies were included. RESULTS: The GRADE quality of evidence was consistently low or very low, primarily because none of the risk ratios (RR) for the risk of sPTD at <37 weeks were statistically significant. Concerning treatment with metronidazole, RR was 1.11 (95% CI 0.93-1.34) in low-risk pregnancies and 0.96 (95% CI 0.78-1.18) in high risk pregnancies. Concerning treatment with clindamycin at any gestational age, the RR was 0.87 (95% CI 0.73-1.05). CONCLUSION: This systematic review gives a strong recommendation against treatment with metronidazole and a weak recommendation against treatment with clindamycin to reduce the sPTD rate in both high-risk and low-risk pregnancies with BV. PMID- 27258799 TI - Small molecule ligand docking to genotype specific bundle structures of hepatitis C virus (HCV) p7 protein. AB - The genome of hepatitis C virus encodes for an essential 63 amino acid polytopic protein p7 of most likely two transmembrane domains (TMDs). The protein is identified to self-assemble thereby rendering lipid membranes permeable to ions. A series of small molecules such as adamantanes, imino sugars and guanidinium compounds are known to interact with p7. A set of 9 of these small molecules is docked against hexameric bundles of genotypes 5a (bundle-5a) and 1b (bundle-1b) using LeadIT. Putative sites for bundle-5a are identified within the pore and at pockets on the outside of the bundle. For bundle-1b preferred sites are found at the site of the loops. Binding energies are in favour of the guanidinium compounds. Rescoring of the identified poses with HYDE reveals a dehydration penalty for the guanidinium compounds, leaving the adamantanes and imino sugar in a better position. Binding energies calculated by HYDE and those by LeadIT indicate that all compounds are moderate binders. PMID- 27258800 TI - Robotic Single-Port Laparoscopic Cholecystectomy Is Safe but Faces Technical Challenges. AB - BACKGROUND: For cholecystectomy, multiport laparoscopy is the recommended surgical approach. Single-port laparoscopy (SPL) was introduced to reduce postoperative pain and provide better cosmetic results, but has technical disadvantages. Robotic SPL (RSPL) was developed to overcome these disadvantages. In this prospective study, we aim to describe intraoperative results and postoperative outcomes of RSPL cholecystectomies and evaluate technical aspects of the technique. METHODS: A prospective database of all patients who underwent a RSPL cholecystectomy between January 2012 and December 2014 was analyzed. Intraoperative results and postoperative complications were evaluated. RESULTS: A total of 27 patients underwent RSPL cholecystectomy. Median age was 59 (20-78) years and median body mass index was 25 (19-35) kg/m2. The majority of patients had American Society of Anesthesiologists (ASA) II classification (67%) and 89% underwent surgery for cholecystolithiasis or cholecystitis. The median operating time was 81 (41-115) minutes. Conversion to a multiport procedure occurred in 2; one due to insufficient length of the robotic instruments. In the second and third patients, conversion to an open procedure was necessary due to inadequate exposure caused by liver cirrhosis and purulent ascites, respectively. In seven procedures, spill occurred due to rupture of the gallbladder. Postoperative complications occurred in 4 patients, including 1 bleeding (no reintervention), 1 peritonitis, and 2 wound infections. After a median follow-up of 33 (10-44) months, 5 (19%) trocar-site hernias were seen. CONCLUSION: RSPL cholecystectomy is feasible, however, encountered by technical challenges due to inadequate length of the nonwristed robotic instruments. A high incidence of gallbladder rupture and trocar-site hernias may limit its application. PMID- 27258801 TI - Keeping a lid on calcium uptake. AB - Biochemical assays reveal how three proteins fit together to form the channel that controls the flow of calcium ions into mitochondria. PMID- 27258802 TI - Patterns of Gesture Use in Adolescents With Autism Spectrum Disorder. AB - PURPOSE: The purpose of this study was to examine patterns of spontaneous gesture use in a sample of adolescents with autism spectrum disorder (ASD). METHOD: Thirty-five adolescents with ASD ages 11 to 16 years participated (mean age = 13.51 years; 29 boys, 6 girls). Participants' spontaneous speech and gestures produced during a narrative task were later coded from videotape. Parents were also asked to complete questionnaires to quantify adolescents' general communication ability and autism severity. RESULTS: No significant subgroup differences were apparent between adolescents who did not gesture versus those who produced at least 1 gesture in general communication ability and autism severity. Subanalyses including only adolescents who produced gesture indicated a statistically significant negative association between gesture rate and general communication ability, specifically speech and syntax subscale scores. Adolescents who gestured produced higher proportions of iconic gestures and used gesture mostly to add information to speech. CONCLUSIONS: The findings relate spontaneous gesture use to underlying strengths and weaknesses in adolescents' speech and syntactical language development. More research examining cospeech gesture in fluent speakers with ASD is needed. PMID- 27258804 TI - Keyword Index Volume 38 (2016). PMID- 27258805 TI - Laser Therapy and Muscle Fatigue: A Promising Research Area. PMID- 27258806 TI - Aerobic, resistance and combined training and detraining on body composition, muscle strength, lipid profile and inflammation in coronary artery disease patients. AB - Fifty-six elderly individuals diagnosed with coronary artery disease participated in the study and were divided into four groups: an aerobic exercise group, a resistance exercise group, a combined (aerobic + resistance) exercise group and a control group. The three exercise groups participated in 8 months of exercise training. Before, at 4 and at 8 months of the training period as well as at 1, 2 and 3 months after training cessation, muscle strength was measured and blood samples were collected. The resistance exercise caused significant increases mainly in muscle strength whereas aerobic exercise caused favourable effects mostly on lipid and apolipoprotein profiles. On the other hand, combined exercise caused significant favourable effects on both physiological (i.e. muscle strength) and biochemical (i.e. lipid and apolipoprotein profile and inflammation status) parameters, while the return to baseline values during the detraining period was slower compared to the other exercise modalities. PMID- 27258807 TI - Piloting Augmented Reality Technology to Enhance Realism in Clinical Simulation. AB - We describe a pilot study that incorporated an innovative hybrid simulation designed to increase the perception of realism in a high-fidelity simulation. Prelicensure students (N = 12) cared for a manikin in a simulation lab scenario wearing Google Glass, a wearable head device that projected video into the students' field of vision. Students reported that the simulation gave them confidence that they were developing skills and knowledge to perform necessary tasks in a clinical setting and that they met the learning objectives of the simulation. The video combined visual images and cues seen in a real patient and created a sense of realism the manikin alone could not provide. PMID- 27258808 TI - Relationships Between eHealth Literacy and Health Behaviors in Korean Adults. AB - The Internet is a useful and accessible source for health-related information for modern healthcare consumers. Individuals with adequate eHealth literacy have an incentive to use the Internet to access health-related information, and they consider themselves capable of using Web-based knowledge for health. This cross sectional study aimed to describe the relationship between eHealth literacy and health behaviors. A total of 230 adults aged 18 to 39 years and residing in South Korea participated in the study. The mean (SD) score for eHealth literacy was 25.52 (4.35) of a total possible score of 40. The main source of health information was the Internet. Using hierarchical linear regression, the results showed that eHealth literacy was the strongest predictor of health behaviors after adjusting for general characteristics. These findings indicate that eHealth literacy can be an important factor in promoting individual health behaviors. Further research on eHealth literacy and actual health behaviors including intention and self-reported health behaviors are required to explain the impact of eHealth literacy on overall health status. PMID- 27258809 TI - Effect of various storage conditions on the stability of quinolones in raw milk. AB - Research on the storage stability of antibiotic residues in milk is important for method development or validation, milk quality control and risk assessment during screening, confirmation, qualitative or quantitative analysis. This study was conducted using UPLC-MS/MS to determine the stability of six quinolones - ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin (SAR), difloxacin (DIF) and flumequine (FLU) - in raw milk stored under various conditions to investigate if quinolones degrade during storage of milk, and finally to determine optimal storage conditions for analysis and scientific risk assessment of quinolone residues in raw milk. The storage conditions included different temperatures and durations (4 degrees C for 4, 8, 24 and 48 h; -20 degrees C for 1, 7 and 30 days; -80 degrees C for 1, 7 and 30 days), thawing temperatures (25, 40 and 60 degrees C), freeze-thaw cycles (1-5), and the addition of different preservatives (sodium thiocyanate, sodium azide, potassium dichromate, bronopol and methanal). Most quinolones exhibited high stability at 4 degrees C for up to 24 h, but began to degrade after 48 h. In addition, no degradation of quinolones was seen when milk samples were stored at -20 degrees C for up to 7 days; however, 30 days of storage at -20 degrees C resulted in a small amount of degradation (about 30%). Similar results were seen when samples were stored at -80 degrees C. Moreover, no losses were observed when frozen milk samples were thawed at 25, 40 or 60 degrees C. All the quinolones of interest, except sarafloxacin, were stable when milk samples were thawed at 40 degrees C once and three times, but unstable after five freeze-thaw cycles. Preservatives affected the stability of quinolones, but the effects differed depending on the preservative and quinolone. The results of this study indicate optimum storage protocols for milk samples, so that residue levels reflect those at the time of initial sample analysis, and should improve surveillance programmes for quinolones in raw milk. PMID- 27258810 TI - A syn-Selective Aza-Aldol Reaction of Boron Aza-Enolates Generated from N Sulfonyl-1,2,3-Triazoles and 9-BBN-H. AB - A syn-selective aza-aldol reaction of boron aza-enolates, generated from N sulfonyl-1,2,3-triazoles and 9-BBN-H, is reported. It provides a sequential one pot procedure for the stereoselective construction of 1,3-amino alcohols, having contiguous stereocenters, starting from terminal alkynes. PMID- 27258811 TI - The effects of visual feedback during a rhythmic weight-shifting task in patients with Parkinson's disease. AB - Augmented visual feedback (VF) may offer benefits similar to those of rhythmic external cues in alleviating some mobility-related difficulties in individuals with Parkinson's disease (PD). However, due to an impaired ability to reweigh sensory information under changing circumstances, subjects with PD may be rather vulnerable to incongruity of visual information. In the present study, we investigated whether VF is indeed effective in improving motor functioning in a weight-shifting task during upright stance, and whether subjects with PD are affected more by incongruent VF than healthy controls. Participants performed sideways swaying motions based on tracking of real-time and delayed VF - the first providing congruent, and hence more accurate, visual information than the latter. We analyzed center-of-pressure signals patterns for 28 individuals with PD and 16 healthy, age- and gender-matched controls by estimating task accuracy, movement pattern variability, and normalized movement amplitude. For conditions without feedback and with real-time feedback, subjects with PD performed lateral swaying motions with greater error (F(1, 42)=12.065, p=.001) and with more variable movement patterns than healthy controls (F(1, 24)=113.086, p<.001). Error change scores revealed that patients with PD were nevertheless still able to use VF to improve tracking performance (t(24)=-2.366, p=.026). However, whereas controls were able to adapt to a certain amount of visual incongruity, patients with PD were not. Instead, movement amplitude was significantly reduced in this group (F(1.448, 60.820)=17.639, p<.001). By reducing movement amplitude, subjects with PD appear to resort to a 'conservative' strategy to minimize performance breakdown. PMID- 27258812 TI - Assessment of CTLA-4 Deficiency-Related Autoimmune Choroidopathy Response to Abatacept. PMID- 27258813 TI - Association of Using Hearing Aids or Cochlear Implants With Changes in Depressive Symptoms in Older Adults. AB - IMPORTANCE: Hearing loss is a common health problem in older adults that is strongly associated with the development of depression. Previous cross-sectional studies have reported lower odds of depression among individuals who use hearing aids. However, there have been limited prospective studies investigating the effect of hearing loss treatments on depressive symptoms. OBJECTIVE: To investigate the association between treatment with a hearing aid or cochlear implant with depressive symptoms in older adults. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational study was conducted of 113 participants 50 years or older who received hearing aids (n = 63) or cochlear implants (n = 50). Participants were recruited from August 1, 2011, to January 31, 2014, at a tertiary care academic center. INTERVENTION: Hearing aid or cochlear implantation. MAIN OUTCOMES AND MEASURES: Depressive symptoms were evaluated by the 15-item Geriatric Depression Scale (GDS) at baseline and at 6 and 12 months after intervention. The score ranges from 0 to 15, and various scores between 3 and 10 have been used as being suggestive of depression. RESULTS: The median age of the 113 study participants was 69.6 years (interquartile range, 63.5-77.4 years). At baseline, the mean GDS score for the participants was 41% lower (95% CI, 7%-63%) among those receiving hearing aids (mean score, 1.5; 95% CI, 0.7-3.3) compared with those receiving cochlear implants (mean score, 2.6; 95% CI, 1.3 5.1). Cochlear implant recipients' GDS scores improved from baseline to 6 months after treatment by 31% (95% CI, 10%-47%) and from baseline to 12 months after treatment by 38% (95% CI, 18%-54%). Hearing aid recipients' GDS scores improved by 28% (95% CI, 0%-48%) at 6 months after treatment but were not significantly different from baseline at 12 months after treatment (16%; 95% CI, -24% to 43%). CONCLUSIONS AND RELEVANCE: There was a significant improvement in depressive symptoms at 6 months after treatment for patients receiving cochlear implants and hearing aids; this improvement persisted to 12 months for those who received cochlear implants. Further research is warranted to assess the long-term effect of hearing rehabilitation on mental health in older adults. PMID- 27258814 TI - Magnetic compression anastomosis for patients with a disconnected bile duct after living-donor related liver transplantation: a pilot study. AB - BACKGROUND AND STUDY AIM: We present the use of the magnetic compression anastomosis (MCA) technique for treatment of disconnected bile duct after living donor related liver transplantation (LDLT) using the recently introduced through the-scope magnet. PATIENTS AND METHODS: The MCA technique was used in patients with disconnected bile duct who could not be treated with either percutaneous or endoscopic procedures. All patients already had a percutaneous external biliary drainage catheter before the procedure. The magnet was placed percutaneously into the proximal side of the obstruction by pushing a 5-Fr catheter over a guidewire. Concurrently, endoscopic retrograde cholangiopancreatography (ERCP) including endoscopic papillary sphincterotomy was performed. The sister magnet was then carefully advanced to the opposite side of the obstruction with a 5-Fr catheter over a guidewire. After the confirmation of biliary recanalization, a guidewire was passed through the stricture and a percutaneous dilation of the stricture was performed with a balloon-tipped catheter. Endoscopic balloon dilation of the stricture, insertion of two plastic stents and the removal of the internal drainage catheter were performed during the first ERCP session. Stent exchange and multiple side-by-side stent placements were planned at regular intervals (3 monthly) for all patients. RESULTS: A total of six LDLT patients with disconnected bile duct (aged 37 - 68, four men) underwent the MCA technique between September 2014 and July 2015. Biliary recanalization was achieved 13 - 42 days after the magnet placement procedure. The success rate of the procedure was 100 %. CONCLUSIONS: The MCA technique using a small magnet (diameter 2.4 mm) is effective and useful in LDLT patients with disconnected bile duct. PMID- 27258815 TI - Giant insulinoma in a 15-year-old man: A case report. AB - INTRODUCTION: Giant insulinomas are extremely rare pancreatic neuroendocrine tumor. PRESENTATION OF CASE: A 15-year-old man presenting with acute onset of lightheadedness was found to have serum glucose of 1.5mmol/L. The blood collected from the hypoglycemic episode showed an inappropriately high insulin and C peptide level. Abdominal computerized tomography showed a 12.5cm well-defined, lobulated hypervascular mass at pancreatic tail, without any evidence of metastasis. En bloc resection with distal pancreatectomy, and splenectomy was successfully performed. The pathological examination confirmed insulinoma, with benign characteristics. Follow-up after the procedure revealed neither hypoglycemic, nor hyperglycemia. CONCLUSION: We report the youngest case of a giant insulinoma. Despite the size of the tumor, the pathological report confirmed the benign characteristics. However, long-term follow-up is still essential to detect recurrence in the future. PMID- 27258816 TI - Struma Ovarii With Malignant Transformation and Germline KIT Mutation: A Case Report With Review of the Literature. AB - Struma ovarii accounts for 5% of ovarian teratomas. Malignant transformation occurs in <0.3%, however, the underlying molecular mechanism is unknown. We report a patient with follicular variant and tall cell variant of papillary thyroid carcinoma (PTC) arising from struma ovarii and coexisting incidental PTC in the thyroid. Mutation analysis by next-generation sequencing identified a novel germline mutation, KIT p.V530I mutation in the tumors and normal ovarian and thyroid tissue. Immunohistochemical staining showed loss of KIT expression in the PTCs. Activating mutations in KIT play an important role in diagnosis and prognosis of multiple malignancies including mastocytosis, gastrointestinal stromal tumors, and a subset of melanoma and acute myeloid leukemia. The p.V530I mutation has only been reported in 3 previous cases: acute myeloid leukemia, aggressive fibromatosis, and adenocarcinoma of the colon. In the case of aggressive fibromatosis, the patient responded well to imatinib treatment. KIT mutations have never been reported in thyroid carcinomas. This is the first case of PTC-harboring KIT mutation. Although more work needs to be done to elucidate the significance of this germline mutation, the response of the fibromatosis patient to imatinib may shed light on targeted therapy in PTC harboring this mutation. PMID- 27258817 TI - A focus group study of chiropractic students following international service learning experiences. AB - OBJECTIVE: One objective of chiropractic education is to cultivate clinical confidence in novice practitioners. The purpose of this qualitative study was to describe how participation in a short-term international service learning experience changed perceptions of clinical confidence in senior chiropractic students. METHODS: Seventeen senior chiropractic students participated in 4 moderated focus group sessions within 4 months after a clinical educational opportunity held in international settings. Participants answered standard questions on how this educational experience may have changed their clinical confidence. Two investigators performed qualitative thematic analysis of the verbatim transcripts to identify core concepts and supporting themes. RESULTS: The core concept was transformation from an unsure student to a confident doctor. The service learning experience allowed students to deliver chiropractic treatment to patients in a real-world setting, engage in frequent repetitions of technical skills, perform clinical decision-making and care coordination, and communicate with patients and other health professionals. Students described increased clinical confidence in 9 competency areas organized within 3 domains: (1) chiropractic competencies including observation, palpation, and manipulation; (2) clinical competencies including problem solving, clinic flow, and decision making; and (3) communication competencies, including patient communication, interprofessional communication, and doctor-patient relationship. Students recommended that future service learning programs include debriefing sessions similar to the experience offered by these focus groups to enhance student learning. CONCLUSION: Senior chiropractic students who participated in an international service learning program gained confidence and valuable practical experience in integrating their chiropractic, clinical, and communication skills for their future practices. PMID- 27258819 TI - Down-regulation of glutamatergic terminals (VGLUT1) driven by Abeta in Alzheimer's disease. AB - Alzheimer's disease (AD) is characterized phenotypically by memory impairment, histologically by accumulation of pTau and beta-amyloid peptide and morphologically by a loss of nerve terminals in cortical and hippocampal regions. As glutamate is the principle excitatory neurotransmitter of the central nervous system (CNS), the glutamatergic system may play an important role in AD. To date, not many studies have addressed the deleterious effects of Abeta on glutamatergic terminals; therefore the aim of this study was to investigate how Abeta affects glutamatergic terminals and to assess the extent to which alterations in the glutamatergic neurotransmission could impact susceptibility to the illness. The present study shows that Abeta caused a loss of glutamatergic terminals, measured by VGLUT1 protein levels, in Tg2576 primary cell cultures, Tg2576 mice and AD patient brains, and also when Abeta was added exogenously to hippocampal cell cultures. Interestingly, no correlation was found between cognition and decreased VGLUT1 levels. Moreover, when Abeta1-42 was intracerebroventricularlly administered into VGLUT1+/- mice, altered synaptic plasticity and increased neuroinflammation was observed in the hippocampus of those animals. In conclusion, the present study not only revealed susceptibility of glutamatergic nerve terminals to Abeta induced toxicity but also underlined the importance of VGLUT1 in the progression of AD, as the decrease of this protein levels could increase the susceptibility to subsequent deleterious inputs by exacerbating Abeta induced neuroinflammation and synaptic plasticity disruption. (c) 2016 Wiley Periodicals, Inc. PMID- 27258818 TI - U-Shaped Association between Plasma Manganese Levels and Type 2 Diabetes. AB - BACKGROUND: Manganese is both an essential element and a known toxicant, and it plays important roles in many mechanisms in relation to type 2 diabetes (T2D). However, epidemiological studies of this relationship are rare. OBJECTIVE: We investigated the association between plasma manganese and newly diagnosed T2D as well as whether the association could be modified by manganese superoxide dismutase (MnSOD) polymorphisms. METHODS: We conducted a case-control study of 3,228 participants in China: 1,614 T2D patients and 1,614 controls. Concentrations of plasma magnesium were measured, and all participants were genotyped for the MnSOD Val16Ala polymorphism (rs4880). RESULTS: A U-shaped association was observed between plasma manganese and T2D, with increased odds ratios (ORs) in relation to either low or high plasma manganese levels. Compared with the middle tertile, the multivariate-adjusted ORs [95% confidence intervals (CIs)] of T2D associated with the lowest tertile and the highest tertile of plasma manganese were 1.89 (1.53, 2.33) and 1.56 (1.23, 1.97), respectively. In spline analysis, the U-shaped association was consistently indicated, with the lowest odds of T2D at the plasma manganese concentration of 4.95 MUg/L. Minor allele frequencies (C allele) of the MnSOD Val16Ala polymorphism (rs4880) in the normal glucose tolerance (NGT) and the T2D groups were 13.57% and 14.50%, respectively. The MnSOD rs4880 polymorphism was not associated with T2D, and no interaction was found between plasma manganese and the MnSOD rs4880 polymorphism in relation to T2D. CONCLUSIONS: Our results suggested a U-shaped association between plasma manganese and T2D; both low and high levels of plasma manganese were associated with higher odds of newly diagnosed T2D. The U-shaped association was not modified by the MnSOD rs4880 polymorphism. Citation: Shan Z, Chen S, Sun T, Luo C, Guo Y, Yu X, Yang W, Hu FB, Liu L. 2016. U-shaped association between plasma manganese levels and type 2 diabetes. Environ Health Perspect 124:1876 1881; http://dx.doi.org/10.1289/EHP176. PMID- 27258820 TI - The unicellular fungal tool RhoTox for risk assessments in groundwater systems. AB - The recent inclusion of yeasts in environmental monitoring recognizes their ecological significance and sensitivity to toxicants. Here we present a robust and simple two-step toxicity assay and demonstrate the sensitivity of an ubiquitous groundwater yeast, Rhodotorula minuta, to a range of metals and metalloids. The test species was sensitive to copper with a 24h EC50 of 35ug Cu/L, followed in order of decreasing sensitivity by zinc, chromium (VI) and arsenic (EC50 4.40mg As (III)/L). The strain demonstrated an unexpected tolerance to chromium (VI), having an EC50 value (3.45mg Cr (VI)/L) similar to that of arsenic. The inclusion of a unicellular, microbial test-species into the suite of existing multicellular test species for toxicity evaluation is a key step towards strengthening the assessment of risk for groundwater ecosystems. PMID- 27258821 TI - Association of serum interleukin-6 with mental health problems in children exposed to perinatal complications and social disadvantage. AB - There is consistent evidence that inflammation is involved in mental disorders pathogenesis. Herein, using data from the High Risk Cohort Study for Psychiatric Disorders, we investigated the relationship between parental mood disorders (PMD), environmental factors, serum interleukin-6 (IL6) and mental health problems in children aged 6-12. We measured the serum levels of IL6 in 567 children. Information related to socio-demographic characteristics, mental health problems and multiple risk factors, as well as parent's psychiatric diagnosis, was captured. We evaluated two groups of environmental risk factors (i.e. perinatal complications and social disadvantage) using a cumulative risk model. Results showed that higher serum levels of IL6 were associated with PMD (RR=1.072, p=0.001), perinatal complications (RR=1.022, p=0.013) and social disadvantage (RR=1.024, p=0.021). There was an interaction between PMD and social disadvantage (RR=1.141, p=0.021), as the effect of PMD on IL6 was significantly higher in children exposed to higher levels of social disadvantage. Moreover, there was a positive correlation between IL6 and mental health problems (RR=1.099, p=0.026), which was moderated by exposure to perinatal complications or social disadvantage (RR=1.273, p=0.015 and RR=1.179, p=0.048, respectively). In conclusions, there is evidence of a differential inflammatory activation in children with PMD and exposure to environmental risk factors, when compared to matched peers. Systemic inflammation may be involved in the pathway linking familial risk and mental health problems. PMID- 27258822 TI - Immune cells from patients with psoriasis are defective in inducing indoleamine 2,3-dioxygenase expression in response to inflammatory stimuli. AB - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that suppresses the immune response. The role of IDO as a negative regulator of inflammatory responses has been documented in several experimental autoimmune diseases. OBJECTIVES: To explore the regulation of IDO by immune cells in psoriasis and its relation with disease severity. METHODS: The expression and activity of IDO were assessed by reverse-transcriptase polymerase chain reaction, flow cytometry and high-performance liquid chromatography in peripheral blood of patients with moderate-to-severe plaque-type psoriasis. The ability of immune cells to express IDO in response to inflammatory stimuli was studied. The functional role of IDO expression was evaluated in a regulatory T cell (Treg) differentiation assay, using cocultures of immature monocyte-derived dendritic cells with autologous peripheral CD4+ T cells. RESULTS: Analysis of the kynurenine-to-tryptophan ratio in serum samples indicated higher IDO activity in patients with psoriasis than in healthy controls. However, correlation studies showed lower IDO activity in those patients with higher Psoriasis Area and Severity Index (PASI). Although myeloid dendritic cells from patients with psoriasis expressed higher levels of IDO than those from healthy controls, these cells did not upregulate IDO in response to a combination of tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6 cytokines. The defective expression of IDO correlated with PASI. Immature monocyte-derived dendritic cells from patients with psoriasis also expressed low levels of IDO and induced CD4+ Treg differentiation poorly. CONCLUSIONS: Immune cells from patients with psoriasis have a defect in upregulating IDO in response to inflammation associated with the severity of psoriasis. PMID- 27258823 TI - Internet-Based Survivorship Care Plans for Adult Survivors of Childhood Cancer: A Pilot Study. AB - Survivorship care plans (SCPs) provide health information to survivors and providers. An existing internet-based SCP generator was adapted to incorporate guidelines for adult survivors of pediatric leukemia and lymphoma. Survivors created an SCP online and completed a survey. Survivors (N = 30) took an average of 10 minutes to complete the SCP. The majority (95%) found the platform easy to use, would recommend it to others (85%), and intended to share SCP with their healthcare team (90%). Thus, a patient-generated internet-based SCP for adult survivors of childhood cancer may be a feasible tool to improve consistency of information for survivors and their providers. PMID- 27258824 TI - Rh-Catalyzed Direct Amination of Unactivated C(sp(3) )-H bond with Anthranils Under Mild Conditions. AB - C-N Bond formation is of great significance due to the ubiquity of nitrogen containing compounds. Here, a mild and efficient Rh(III) -catalyzed C(sp(3) )-H aryl amination reaction is reported. Anthranil is employed as the nitrogen source with 100 % atom efficiency. This C-H amination reaction exhibits broad substrate scope without using any external oxidants. Mechanistic studies including rhodacycle intermediates, H-D exchange, kinetic isotope effect (KIE) experiments, and in situ IR are presented. PMID- 27258838 TI - From a Sequential to a Concurrent Reaction in Aqueous Medium: Ruthenium-Catalyzed Allylic Alcohol Isomerization and Asymmetric Bioreduction. AB - The ruthenium-catalyzed redox isomerization of allylic alcohols was successfully coupled with the enantioselective enzymatic ketone reduction (mediated by KREDs) in a concurrent process in aqueous medium. The overall transformation, formally the asymmetric reduction of allylic alcohols, took place with excellent conversions and enantioselectivities, under mild reaction conditions, employing commercially and readily available catalytic systems, and without external coenzymes or cofactors. Optimization resulted in a multistep approach and a genuine cascade reaction where the metal catalyst and biocatalyst coexist from the beginning. PMID- 27258839 TI - Formation of Benzimidazoisoquinolinium and Benzimidazoisoindolinum Cyclic Systems by the Reaction of 2-(2-Alkynylphenyl)benzimidazoles with Iodine and Iodine Iodine Interaction Including Halogen Bonding in Their Crystal Structures. AB - The reaction of 2-(2-alkynylphenyl)benz[d]imidazoles with molecular iodine constructed 5- and 6-membered rings as novel organic salts in high yield. The constituted number of ring systems was influenced by the substituent at the triple bond: 6-membered rings were formed from compounds bearing aryl substituents, whereas 5-membered ones were obtained from compounds with hydrogen or alkyl substituents. The products were obtained with triiodide as a counteranion; however, compounds with iodide were also obtainable under certain conditions. We also revealed that they had an iodine-iodine interaction included in halogen bonding between an iodo moiety of the cation and a triiodide or iodide of the counteranion. The iodine-iodine interaction was formed with greater preference than the electrostatic interaction between the cationic atom and triiodide or iodide. PMID- 27258841 TI - A Hidden Markov Model Approach to the Problem of Heuristic Selection in Hyper Heuristics with a Case Study in High School Timetabling Problems. AB - Operations research is a well-established field that uses computational systems to support decisions in business and public life. Good solutions to operations research problems can make a large difference to the efficient running of businesses and organisations and so the field often searches for new methods to improve these solutions. The high school timetabling problem is an example of an operations research problem and is a challenging task which requires assigning events and resources to time slots subject to a set of constraints. In this article, a new sequence-based selection hyper-heuristic is presented that produces excellent results on a suite of high school timetabling problems. In this study, we present an easy-to-implement, easy-to-maintain, and effective sequence-based selection hyper-heuristic to solve high school timetabling problems using a benchmark of unified real-world instances collected from different countries. We show that with sequence-based methods, it is possible to discover new best known solutions for a number of the problems in the timetabling domain. Through this investigation, the usefulness of sequence-based selection hyper-heuristics has been demonstrated and the capability of these methods has been shown to exceed the state of the art. PMID- 27258840 TI - Neocortex expansion in development and evolution - from cell biology to single genes. AB - Neocortex expansion in development and evolution reflects an increased and prolonged activity of neural progenitor cells. Insight into key aspects of the underlying cell biology has recently been obtained. First, the restriction of apical progenitors to undergo mitosis at the ventricular surface is overcome by generation of basal progenitors, which are free to undergo mitosis at abventricular location, typically the subventricular zone. This process involves basolateral ciliogenesis, delamination from the apical adherens junction belt, and loss of apical cell polarity. Second, proliferative capacity of basal progenitors is supported by self-produced extracellular matrix constituents, which in turn promote growth factor signalling. Humans amplify these processes by characteristic alterations in expression of key regulatory genes (PAX6), and via human-specific genes (ARHGAP11B). PMID- 27258842 TI - Hybrid Self-Adaptive Evolution Strategies Guided by Neighborhood Structures for Combinatorial Optimization Problems. AB - This article presents an Evolution Strategy (ES)--based algorithm, designed to self-adapt its mutation operators, guiding the search into the solution space using a Self-Adaptive Reduced Variable Neighborhood Search procedure. In view of the specific local search operators for each individual, the proposed population based approach also fits into the context of the Memetic Algorithms. The proposed variant uses the Greedy Randomized Adaptive Search Procedure with different greedy parameters for generating its initial population, providing an interesting exploration-exploitation balance. To validate the proposal, this framework is applied to solve three different [Formula: see text]-Hard combinatorial optimization problems: an Open-Pit-Mining Operational Planning Problem with dynamic allocation of trucks, an Unrelated Parallel Machine Scheduling Problem with Setup Times, and the calibration of a hybrid fuzzy model for Short-Term Load Forecasting. Computational results point out the convergence of the proposed model and highlight its ability in combining the application of move operations from distinct neighborhood structures along the optimization. The results gathered and reported in this article represent a collective evidence of the performance of the method in challenging combinatorial optimization problems from different application domains. The proposed evolution strategy demonstrates an ability of adapting the strength of the mutation disturbance during the generations of its evolution process. The effectiveness of the proposal motivates the application of this novel evolutionary framework for solving other combinatorial optimization problems. PMID- 27258843 TI - Thoughts from an opioid prescriber. PMID- 27258844 TI - When and how to treat childhood immune thrombocytopenia. AB - Childhood immune thrombocytopenia is an autoimmune process resulting in an isolated thrombocytopenia that puts the child at risk for bleeding and can negatively impact quality of life. Pharmacologic intervention aims to stabilize the platelet count, with the goal of achieving hemostasis and maximizing health related quality of life. PMID- 27258845 TI - Esophageal perforation caused by an AMPLATZERTM vascular plug 4 occlusion device. AB - The AMPLATZERTM Vascular Plug 4 (AVP4) is a self-expandable, replaceable occluder made of Nitinol wire mesh, which allows the safe and effective interventional occlusion of medium size vessels. This report describes an infant diagnosed with pulmonary atresia, ventricular septal defect, and multifocal collateral lung perfusion through four major aortopulmonary collateral arteries (MAPCAs). A central aorto-pulmonary shunt was performed at 4 months of age. Because of postoperative pulmonary hyperperfusion, one of the MAPCAs was closed interventionally using a 5 mm AVP4. This MAPCA originated from the descending aorta (DAO) near the fifth thoracic vertebra and ran behind the esophagus to the lower lobe of the right lung. The MAPCA was closed near its origin from the DAO. Four weeks later, the patient presented with severe gastrointestinal bleeding, caused by perforation of the AVP4 into the esophagus. The occluder was extracted surgically, the MAPCA was clipped and the esophageal injury was sutured. To date, there have been no reports describing esophageal perforation due to an AVP4. The perforation in this patient may have been due to implantation of the AVP4 near the aorta in a MAPCA segment located directly in front of the spine and behind the esophagus. Another possible factor may have been the requirement for a gastrointestinal feeding tube. Although the occluder is soft and flexible, the spindle-shaped ends may cause trauma if they are located close to other structures. (c) 2016 Wiley Periodicals, Inc. PMID- 27258846 TI - Reliability of ground reaction forces in the aquatic environment. AB - The aim of this study was to verify the reliability of the kinetic parameters of gait using an underwater force platform. A total of 49 healthy participants with a median age of 21years were included. The kinetic gait data were collected using a 0.6*0.6*0.1m aquatic force plate (Bertec(r)), set in a pool (15*13*1.30m) with a water depth of 1.20m and water temperature of 32.5 degrees C. Participants walked 10m before reaching the platform, which was fixed to the ground. Participants were instructed to step onto the platform with their preferred limb and data from three valid attempts were used to calculate the average values. A 48-h interval between tests was used for the test-retest reliability. Data were analyzed using interclass correlation coefficients (ICC) and results demonstrated that reliability ranged from poor to excellent, with ICC scores of between 0.24 and 0.87 and mean differences between (d-)=-0.01 and 0.002. The highest reliability values were found for the vertical (Fz) and the lowest for the mediolateral components (Fy). In conclusion, the force platform is reliable for assessing the vertical and anteroposterior components of power production rates in water, however, caution should be applied when using this instrument to evaluate the mediolateral component in this environment. PMID- 27258847 TI - Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning. AB - Organophosphorus (OP) pesticide poisoning is a leading cause of morbidity and mortality in the developing world, affecting an estimated three million people annually. Much of the morbidity is directly related to muscle weakness, which develops 1-4 days after poisoning. This muscle weakness, termed the intermediate syndrome (IMS), leads to respiratory, bulbar, and proximal limb weakness and frequently necessitates the use of mechanical ventilation. While not entirely understood, the IMS is most likely due to persistently elevated acetylcholine (ACh), which activates nicotinic ACh receptors at the neuromuscular junction (NMJ). Thus, the NMJ is potentially a target-rich area for the development of new therapies for acute OP poisoning. In this manuscript, we discuss what is known about the IMS and studies investigating the use of nicotinic ACh receptor antagonists to prevent or mitigate NMJ dysfunction after acute OP poisoning. PMID- 27258848 TI - Geochemistry and Mineralogy of Western Australian Salt Lake Sediments: Implications for Meridiani Planum on Mars. AB - Hypersaline lakes are characteristic for Western Australia and display a rare combination of geochemical and mineralogical properties that make these lakes potential analogues for past conditions on Mars. In our study, we focused on the geochemistry and mineralogy of Lake Orr and Lake Whurr. While both lakes are poor in organic carbon (<1%), the sediments' pH values differ and range from 3.8 to 4.8 in Lake Orr and from 5.4 to 6.3 in Lake Whurr sediments. Lake Whurr sediments were dominated by orange and red sediment zones in which the main Fe minerals were identified as hematite, goethite, and tentatively jarosite and pyrite. Lake Orr was dominated by brownish and blackish sediments where the main Fe minerals were goethite and another paramagnetic Fe(III)-phase that could not be identified. Furthermore, a likely secondary Fe(II)-phase was observed in Lake Orr sediments. The mineralogy of these two salt lakes in the sampling area is strongly influenced by events such as flooding, evaporation, and desiccation, processes that explain at least to some extent the observed differences between Lake Orr and Lake Whurr. The iron mineralogy of Lake Whurr sediments and the high salinity make this lake a suitable analogue for Meridiani Planum on Mars, and in particular the tentative identification of pyrite in Lake Whurr sediments has implications for the interpretation of the Fe mineralogy of Meridiani Planum sediments. KEY WORDS: Western Australia-Salt lakes-Jarosite-Hematite-Pyrite-Mars analogue. Astrobiology 16, 525-538. PMID- 27258849 TI - Low-density lipoprotein receptor-related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation. AB - The LDL family of receptors and its member low-density lipoprotein receptor related protein 1 (LRP1) have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation, and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously, we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation. In the current study, we show that LeX-glycosylated LRP1 is also expressed in the stem cell compartment of the developing spinal cord and has broader functions in the developing CNS. We have investigated the basic properties of LRP1 conditional knockout on the neural stem/progenitor cells (NSPCs) from the cortex and the spinal cord, created by means of Cre-loxp-mediated recombination in vitro. The functional status of LRP1-deficient cells has been studied using proliferation, differentiation, and apoptosis assays. LRP1 deficient NSPCs from both CNS regions demonstrated altered differentiation profiles. Their differentiation capacity toward oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes and neurons was reduced. In contrast, astrocyte differentiation was promoted. Moreover, LRP1 deletion had a negative effect on NSPCs proliferation and survival. Our observations suggest that LRP1 facilitates NSPCs differentiation via interaction with apolipoprotein E (ApoE). Upon ApoE4 stimulation wild type NSPCs generated more oligodendrocytes, but LRP1 knockout cells showed no response. The effect of ApoE seems to be independent of cholesterol uptake, but is rather mediated by downstream MAPK and Akt activation. GLIA 2016 GLIA 2016;64:1363-1380. PMID- 27258850 TI - A New Ir-NHC Catalyst for Signal Amplification by Reversible Exchange in D2 O. AB - NMR signal amplification by reversible exchange (SABRE) has been observed for pyridine, methyl nicotinate, N-methylnicotinamide, and nicotinamide in D2 O with the new catalyst [Ir(Cl)(IDEG)(COD)] (IDEG=1,3-bis(3,4,5 tris(diethyleneglycol)benzyl)imidazole-2-ylidene). During the activation and hyperpolarization steps, exclusively D2 O was used, resulting in the first fully biocompatible SABRE system. Hyperpolarized (1) H substrate signals were observed at 42.5 MHz upon pressurizing the solution with parahydrogen at close to the Earth's magnetic field, at concentrations yielding barely detectable thermal signals. Moreover, 42-, 26-, 22-, and 9-fold enhancements were observed for nicotinamide, pyridine, methyl nicotinate, and N-methylnicotinamide, respectively, in conventional 300 MHz studies. This research opens up new opportunities in a field in which SABRE has hitherto primarily been conducted in CD3 OD. This system uses simple hardware, leaves the substrate unaltered, and shows that SABRE is potentially suitable for clinical purposes. PMID- 27258852 TI - The Expression of B-Type Natriuretic Peptide After CaCl2-Induced Arrhythmias in Rats. AB - To investigate the patterns of B-type natriuretic peptide (BNP) expression after arrhythmia, BNP was assessed at different time points (0 minute, 10 minutes, 30 minutes, 1 hour, 3 hours, and 6 hours) in CaCl2-induced arrhythmia in rats through various methods such as immunohistochemistry, Western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. Immunohistochemistry results showed that the expression of BNP in the endocardium was higher than that in the epicardium in rats undergoing sustained arrhythmias. The BNP-to-GAPDH (glyceraldehyde-3-phosphate dehydrogenase) ratios determined by Western blotting analysis revealed no change at 0 minute but increased at 10 minutes and reached the first peak (0.48 [0.03]) at 30 minutes. After a brief decline, the second peak was observed at 6 hours (0.54 [0.03]). Similar patterns of BNP messenger RNA expression were also observed by quantitative real-time polymerase chain reaction. The plasma BNP concentrations did not change after initial bouts of cardiac arrhythmias but significantly increased 30 minutes after CaCl2 injections. The results demonstrate that arrhythmia causes an elevation of BNP in the myocardium and blood, and BNP messenger RNA increases in initial arrhythmia while its protein in myocardium and plasma does not; however, both of them were elevated after sustained arrhythmia. Such an elevated BNP expression, which is directly related to the severity and duration of the arrhythmias, may suggest the existence of fatal arrhythmia in sudden cardiac death. PMID- 27258853 TI - Insights into the Hydrolytic Polymerization of Trimethoxymethylsilane. Crystal Structure of (MeO)2MeSiONa. AB - The commercially practiced conversion of trimethoxymethylsilane (MTM) to [OSi(OMe)Me)]n polymers and resins is assumed to proceed via the silanol (MeO)2MeSiOH. Access to this crucial silanol is gained via the synthesis of (MeO)2MeSiONa, the first methoxysilanoate to be crystallographically characterized. Mild protonation of this silanoate gives (MeO)2MeSiOH, which is shown to condense with (MeO)2MeSiOH but not with MTM. Condensation generates reactive disiloxanols but does not produce symmetric disiloxanes. Parallel results were obtained with (MeO)2PhSiOH. PMID- 27258851 TI - Nitrate from Drinking Water and Diet and Bladder Cancer Among Postmenopausal Women in Iowa. AB - BACKGROUND: Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. OBJECTIVES: We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. METHODS: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (NO3-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (NO3-N: 5 mg/L, TTHM: 40 MUg/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C). RESULTS: We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; ptrend = 0.11), and we found significant associations among those exposed >= 4 years to drinking water with > 5 mg/L NO3-N (HR = 1.62; 95% CI: 1.06, 2.47; ptrend = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water NO3-N and HR = 3.48; 95% CI: 1.20, 10.06 and >= 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. CONCLUSIONS: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. Citation: Jones RR, Weyer PJ, DellaValle CT, Inoue Choi M, Anderson KE, Cantor KP, Krasner S, Robien K, Beane Freeman LE, Silverman DT, Ward MH. 2016. Nitrate from drinking water and diet and bladder cancer among postmenopausal women in Iowa. Environ Health Perspect 124:1751-1758; http://dx.doi.org/10.1289/EHP191. PMID- 27258854 TI - Temporal and Triggered Evolution of Host-Guest Characteristics in Amphiphilic Polymer Assemblies. AB - An amphiphilic polymer with cleavable side chain and main chain functional groups has been designed and synthesized. Specific cleavage of either of its functional groups was found to have an effect on the morphology of the assembly. Degradation of the main chain is shown to cause morphology of the supramolecular assembly to evolve with time from a micelle-like assembly to a vesicular assembly. On the other hand, stimulus-induced cleavage of the side chains causes these nanoassemblies to disassemble. These temporal (main chain) and triggered (side chain) degradation processes have implications in the design of degradable polymers as supramolecular scaffolds for biological applications. PMID- 27258855 TI - Oligomeric Amyloid-beta Toxicity Can Be Inhibited by Blocking Its Cellular Binding in Cortical Neuronal Cultures with Addition of the Triphenylmethane Dye Brilliant Blue G. AB - Accumulation of soluble amyloid beta (Abeta) oligomers in the brain has been suggested to cause neurodegeneration associated with Alzheimer's disease (AD). Our previous findings showed that the binding of Abeta trimer and tetramer to neurons is significantly correlated with Abeta-induced neuronal cell death. We propose blocking of neuronal binding of these neurotoxic Abeta oligomers as a therapeutic strategy for preventing this disease. To test this, a nontoxic triphenylmethane dye, Brilliant Blue G (BBG), which has been reported to modulate Abeta aggregation and neurotoxicity, was investigated using mouse primary cortical neuronal cultures treated with photoinduced cross-linked toxic Abeta40 oligomers as well as soluble Abeta40 and Abeta42 peptides. We found that the BBG induced decrease in Abeta binding resulted in a significant decrease in its neurotoxicity. These findings support our hypothesis that disruption of cellular Abeta binding is a promising therapeutic strategy for combating AD. PMID- 27258856 TI - Probabilistically Perfect Cloning of Two Pure States: Geometric Approach. AB - We solve the long-standing problem of making n perfect clones from m copies of one of two known pure states with minimum failure probability in the general case where the known states have arbitrary a priori probabilities. The solution emerges from a geometric formulation of the problem. This formulation reveals that cloning converges to state discrimination followed by state preparation as the number of clones goes to infinity. The convergence exhibits a phenomenon analogous to a second-order symmetry-breaking phase transition. PMID- 27258858 TI - Derandomizing Quantum Circuits with Measurement-Based Unitary Designs. AB - Entangled multipartite states are resources for universal quantum computation, but they can also give rise to ensembles of unitary transformations, a topic usually studied in the context of random quantum circuits. Using several graph state techniques, we show that these resources can "derandomize" circuit results by sampling the same kinds of ensembles quantum mechanically, analogously to a quantum random number generator. Furthermore, we find simple examples that give rise to new ensembles whose statistical moments exactly match those of the uniformly random distribution over all unitaries up to order t, while foregoing adaptive feedforward entirely. Such ensembles-known as t designs-often cannot be distinguished from the "truly" random ensemble, and so they find use in many applications that require this implied notion of pseudorandomness. PMID- 27258857 TI - Geometrical Pumping with a Bose-Einstein Condensate. AB - We realized a quantum geometric "charge" pump for a Bose-Einstein condensate (BEC) in the lowest Bloch band of a novel bipartite magnetic lattice. Topological charge pumps in filled bands yield quantized pumping set by the global topological-properties of the bands. In contrast, our geometric charge pump for a BEC occupying just a single crystal momentum state exhibits nonquantized charge pumping set by local-geometrical-properties of the band structure. Like topological charge pumps, for each pump cycle we observed an overall displacement (here, not quantized) and a temporal modulation of the atomic wave packet's position in each unit cell, i.e., the polarization. PMID- 27258859 TI - Quantum Thermal Transistor. AB - We demonstrate that a thermal transistor can be made up with a quantum system of three interacting subsystems, coupled to a thermal reservoir each. This thermal transistor is analogous to an electronic bipolar one with the ability to control the thermal currents at the collector and at the emitter with the imposed thermal current at the base. This is achieved by determining the heat fluxes by means of the strong-coupling formalism. For the case of three interacting spins, in which one of them is coupled to the other two, that are not directly coupled, it is shown that high amplification can be obtained in a wide range of energy parameters and temperatures. The proposed quantum transistor could, in principle, be used to develop devices such as a thermal modulator and a thermal amplifier in nanosystems. PMID- 27258860 TI - Entanglement Equilibrium and the Einstein Equation. AB - A link between the semiclassical Einstein equation and a maximal vacuum entanglement hypothesis is established. The hypothesis asserts that entanglement entropy in small geodesic balls is maximized at fixed volume in a locally maximally symmetric vacuum state of geometry and quantum fields. A qualitative argument suggests that the Einstein equation implies the validity of the hypothesis. A more precise argument shows that, for first-order variations of the local vacuum state of conformal quantum fields, the vacuum entanglement is stationary if and only if the Einstein equation holds. For nonconformal fields, the same conclusion follows modulo a conjecture about the variation of entanglement entropy. PMID- 27258861 TI - Did LIGO Detect Dark Matter? AB - We consider the possibility that the black-hole (BH) binary detected by LIGO may be a signature of dark matter. Interestingly enough, there remains a window for masses 20M_{?}?M_{bh}?100M_{?} where primordial black holes (PBHs) may constitute the dark matter. If two BHs in a galactic halo pass sufficiently close, they radiate enough energy in gravitational waves to become gravitationally bound. The bound BHs will rapidly spiral inward due to the emission of gravitational radiation and ultimately will merge. Uncertainties in the rate for such events arise from our imprecise knowledge of the phase-space structure of galactic halos on the smallest scales. Still, reasonable estimates span a range that overlaps the 2-53 Gpc^{-3} yr^{-1} rate estimated from GW150914, thus raising the possibility that LIGO has detected PBH dark matter. PBH mergers are likely to be distributed spatially more like dark matter than luminous matter and have neither optical nor neutrino counterparts. They may be distinguished from mergers of BHs from more traditional astrophysical sources through the observed mass spectrum, their high ellipticities, or their stochastic gravitational wave background. Next generation experiments will be invaluable in performing these tests. PMID- 27258862 TI - Large-Scale Distribution of Total Mass versus Luminous Matter from Baryon Acoustic Oscillations: First Search in the Sloan Digital Sky Survey III Baryon Oscillation Spectroscopic Survey Data Release 10. AB - Baryon acoustic oscillations in the early Universe are predicted to leave an as yet undetected signature on the relative clustering of total mass versus luminous matter. A detection of this effect would provide an important confirmation of the standard cosmological paradigm and constrain alternatives to dark matter as well as nonstandard fluctuations such as compensated isocurvature perturbations (CIPs). We conduct the first observational search for this effect, by comparing the number-weighted and luminosity-weighted correlation functions, using the SDSS III BOSS Data Release 10 CMASS sample. When including CIPs in our model, we formally obtain evidence at 3.2sigma of the relative clustering signature and a limit that matches the existing upper limits on the amplitude of CIPs. However, various tests suggest that these results are not yet robust, perhaps due to systematic biases in the data. The method developed in this Letter used with more accurate future data such as that from DESI, is likely to confirm or disprove our preliminary evidence. PMID- 27258863 TI - Double Copies of Fermions as Matter that Interacts Only Gravitationally. AB - Inspired by the recent progress in the field of scattering amplitudes, we discuss hypothetical particles which can be characterized as the double copies of fermions-in the same way gravitons can be viewed as double copies of gauge bosons. As the gravitons, these hypothetical particles interact only through gravitational interactions. We present two equivalent methods for the computation of the relevant scattering amplitudes. The hypothetical particles can be massive and nonrelativistic. PMID- 27258864 TI - Resummed Differential Cross Sections for Top-Quark Pairs at the LHC. AB - We present state of the art resummation predictions for differential cross sections in top-quark pair production at the LHC. They are derived from a formalism which allows the simultaneous resummation of both soft and small-mass logarithms, which endanger the convergence of fixed-order perturbative series in the boosted regime, where the partonic center-of-mass energy is much larger than the mass to the top quark. We combine such a double resummation at next-to-next to-leading logarithmic^{'} (NNLL^{'}) accuracy with standard soft-gluon resummation at next-to-next-to-leading logarithmic accuracy and with next-to leading-order calculations, so that our results are applicable throughout the whole phase space. We find that the resummation effects on the differential distributions are significant, bringing theoretical predictions into better agreement with experimental data compared to fixed-order calculations. Moreover, such effects are not well described by the next-to-next-to-leading-order approximation of the resummation formula, especially in the high-energy tails of the distributions, highlighting the importance of all-orders resummation in dedicated studies of boosted top production. PMID- 27258865 TI - Probing the Small-x Gluon Tomography in Correlated Hard Diffractive Dijet Production in Deep Inelastic Scattering. AB - We investigate the close connection between the quantum phase space Wigner distribution of small-x gluons and the color dipole scattering amplitude, and we propose studying it experimentally in the hard diffractive dijet production at the planned electron-ion collider. The angular correlation between the nucleon recoiled momentum and the dijet transverse momentum probes the nontrivial correlation in the phase space Wigner distribution. This experimental study not only provides us with three-dimensional tomographic pictures of gluons inside high energy protons-it gives a unique and interesting signal for the small-x dynamics with QCD evolution effects. PMID- 27258866 TI - Enhanced Ionization of Embedded Clusters by Electron-Transfer-Mediated Decay in Helium Nanodroplets. AB - We report the observation of electron-transfer-mediated decay (ETMD) involving magnesium (Mg) clusters embedded in helium (He) nanodroplets. ETMD is initiated by the ionization of He followed by removal of two electrons from the Mg clusters of which one is transferred to the He ion while the other electron is emitted into the continuum. The process is shown to be the dominant ionization mechanism for embedded clusters for photon energies above the ionization potential of He. For Mg clusters larger than five atoms we observe stable doubly ionized clusters. Thus, ETMD provides an efficient pathway to the formation of doubly ionized cold species in doped nanodroplets. PMID- 27258867 TI - Carrier-Envelope-Phase Characterization for an Isolated Attosecond Pulse by Angular Streaking. AB - The carrier envelope phase (CEP) is a crucial parameter for a few-cycle laser pulse since it substantially determines the laser waveform. Stepping forward from infrared to extreme ultraviolet (EUV) pulses, we propose a strategy to directly characterize the CEP of an isolated attosecond pulse (IAP) by numerically simulating the tunneling ionization of a hydrogen atom in a combined IAP and phase-stabilized circularly polarized IR laser pulse. The fine modulations of the combined laser fields, due to the variation of the CEP of the IAP, are exponentially enlarged onto the distinct time-dependent tunneling ionization rate. Electrons released at different time with distinct tunneling ionization rates are angularly streaked to different directions. By measuring the resulting photoelectron momentum distribution, the CEP of the IAP can be retrieved. The characterization of the CEP of an IAP will open the possibility of capturing sub EUV-cycle dynamics. PMID- 27258868 TI - Anomalous Diffusion of Dissipative Solitons in the Cubic-Quintic Complex Ginzburg Landau Equation in Two Spatial Dimensions. AB - We demonstrate the occurrence of anomalous diffusion of dissipative solitons in a "simple" and deterministic prototype model: the cubic-quintic complex Ginzburg Landau equation in two spatial dimensions. The main features of their dynamics, induced by symmetric-asymmetric explosions, can be modeled by a subdiffusive continuous-time random walk, while in the case dominated by only asymmetric explosions, it becomes characterized by normal diffusion. PMID- 27258869 TI - Exceptional Contours and Band Structure Design in Parity-Time Symmetric Photonic Crystals. AB - We investigate the properties of two-dimensional parity-time symmetric periodic systems whose non-Hermitian periodicity is an integer multiple of the underlying Hermitian system's periodicity. This creates a natural set of degeneracies that can undergo thresholdless PT transitions. We derive a k.p perturbation theory suited to the continuous eigenvalues of such systems in terms of the modes of the underlying Hermitian system. In photonic crystals, such thresholdless PT transitions are shown to yield significant control over the band structure of the system, and can result in all-angle supercollimation, a PT-superprism effect, and unidirectional behavior. PMID- 27258870 TI - Signature of Wave Chaos in Spectral Characteristics of Microcavity Lasers. AB - We report an experimental investigation on the spectra of fully chaotic and nonchaotic microcavity lasers under continuous-wave operating conditions. It is found that fully chaotic microcavity lasers operate in single mode, whereas nonchaotic microcavity lasers operate in multimode. The suppression of multimode lasing for fully chaotic microcavity lasers is explained by large spatial overlaps of the resonance wave functions that spread throughout the two dimensional cavity due to the ergodicity of chaotic ray orbits. PMID- 27258871 TI - High Power Dynamic Polarization Control Using Plasma Photonics. AB - We report the first experimental demonstration of a plasma wave plate based on laser-induced birefringence. An elliptically polarized input was converted into a nearly ideal circularly polarized beam using an optical system composed of a second laser beam and a plasma. The results are in excellent agreement with linear theory and three-dimensional simulations up to phase delays exceeding pi/4, thus establishing the feasibility of laser-plasma photonic devices that are ultrafast, damage-resistant, and easily tunable. PMID- 27258872 TI - Maximum Proton Energy above 85 MeV from the Relativistic Interaction of Laser Pulses with Micrometer Thick CH_{2} Targets. AB - We present a study of laser-driven ion acceleration with micrometer and submicrometer thick plastic targets. Using laser pulses with high temporal contrast and an intensity of the order of 10^{20} W/cm^{2} we observe proton beams with cutoff energies in excess of 85 MeV and particle numbers of 10^{9} in an energy bin of 1 MeV around this maximum. We show that applying the target normal sheath acceleration mechanism with submicrometer thick targets is a very robust way to achieve such high ion energies and particle fluxes. Our results are backed with 2D particle in cell simulations furthermore predicting cutoff energies above 200 MeV for acceleration based on relativistic transparency. This predicted regime can be probed after a few technically feasible adjustments of the laser and target parameters. PMID- 27258874 TI - Floquet Engineering of Correlated Tunneling in the Bose-Hubbard Model with Ultracold Atoms. AB - We report on the experimental implementation of tunable occupation-dependent tunneling in a Bose-Hubbard system of ultracold atoms via time-periodic modulation of the on-site interaction energy. The tunneling rate is inferred from a time-resolved measurement of the lattice site occupation after a quantum quench. We demonstrate coherent control of the tunneling dynamics in the correlated many-body system, including full suppression of tunneling as predicted within the framework of Floquet theory. We find that the tunneling rate explicitly depends on the atom number difference in neighboring lattice sites. Our results may open up ways to realize artificial gauge fields that feature density dependence with ultracold atoms. PMID- 27258873 TI - Demonstration of Coherent Terahertz Transition Radiation from Relativistic Laser Solid Interactions. AB - Coherent transition radiation in the terahertz (THz) region with energies of sub mJ/pulse has been demonstrated by relativistic laser-driven electron beams crossing the solid-vacuum boundary. Targets including mass-limited foils and layered metal-plastic targets are used to verify the radiation mechanism and characterize the radiation properties. Observations of THz emissions as a function of target parameters agree well with the formation-zone and diffraction model of transition radiation. Particle-in-cell simulations also well reproduce the observed characteristics of THz emissions. The present THz transition radiation enables not only a potential tabletop brilliant THz source, but also a novel noninvasive diagnostic for fast electron generation and transport in laser plasma interactions. PMID- 27258875 TI - Creation of an Ultracold Gas of Ground-State Dipolar ^{23}Na^{87}Rb Molecules. AB - We report the successful production of an ultracold sample of absolute ground state ^{23}Na^{87}Rb molecules. Starting from weakly bound Feshbach molecules formed via magnetoassociation, the lowest rovibrational and hyperfine level of the electronic ground state is populated following a high-efficiency and high resolution two-photon Raman process. The high-purity absolute ground-state samples have up to 8000 molecules and densities of over 10^{11} cm^{-3}. By measuring the Stark shifts induced by external electric fields, we determined the permanent electric dipole moment of the absolute ground-state ^{23}Na^{87}Rb and demonstrated the capability of inducing an effective dipole moment over 1 D. Bimolecular reaction between ground-state ^{23}Na^{87}Rb molecules is endothermic, but we still observed a rather fast decay of the molecular sample. Our results pave the way toward investigation of ultracold molecular collisions in a fully controlled manner and possibly to quantum gases of ultracold bosonic molecules with strong dipolar interactions. PMID- 27258876 TI - Calculation of Projected Bond-Orientational Order Parameters to Quantify Local Symmetries from Transmission Diffraction Data. AB - The bond-orientational order parameters introduced by Steinhardt et al. [Phys. Rev. B 28, 784 (1983)] have been an invaluable measurement tool for assessing short-range order in disordered, close-packed assemblies of particles in which the particle positions are known. In many glassy systems the measurement of particle position is not possible or limited (field of view, thickness, resolution) and the bond-orientational order parameters cannot be measured, or adequately sampled. Here we calculate a set of rotationally averaged, projected bond-orientational order parameters that reflect the symmetries of close-packed particle clusters when projected onto a plane. We show by simulation that these parameters are unique fingerprints that can be directly compared to angular correlations in limited-volume, transmission geometry, diffraction patterns from close-packed glassy assemblies. PMID- 27258877 TI - Emergence of Chirality from Isotropic Interactions of Three Length Scales. AB - Chirality is known to play a pivotal role in determining material properties and functionalities. However, it remains a great challenge to understand and control the emergence of chirality and the related enantioselective process particularly when the building components of the system are achiral. Here we explore the generic mechanisms driving the formation of two-dimensional chiral structures in systems characterized by isotropic interactions and three competing length scales. We demonstrate that starting from isotropic and rotationally invariant interactions, a variety of chiral ordered patterns and superlattices with anisotropic but achiral units can self-assemble. The mechanisms for selecting specific states are related to the length-scale coupling and the selection of resonant density wave vectors. Sample phase diagrams and chiral elastic properties are identified. These findings provide a viable route for predicting chiral phases and selecting the desired handedness. PMID- 27258878 TI - Tuning the Magnetic Quantum Criticality of Artificial Kondo Superlattices CeRhIn_{5}/YbRhIn_{5}. AB - The effects of reduced dimensions and the interfaces on antiferromagnetic quantum criticality are studied in epitaxial Kondo superlattices, with alternating n layers of heavy-fermion antiferromagnet CeRhIn_{5} and seven layers of normal metal YbRhIn_{5}. As n is reduced, the Kondo coherence temperature is suppressed due to the reduction of effective Kondo screening. The Neel temperature is gradually suppressed as n decreases and the quasiparticle mass is strongly enhanced, implying dimensional control toward a quantum critical point. Magnetotransport measurements reveal that a quantum critical point is reached for the n=3 superlattice by applying small magnetic fields. Remarkably, the anisotropy of the quantum critical field is opposite to the expectations from the magnetic susceptibility in bulk CeRhIn_{5}, suggesting that the Rashba spin-orbit interaction arising from the inversion symmetry breaking at the interface plays a key role for tuning the quantum criticality in the two-dimensional Kondo lattice. PMID- 27258879 TI - Stick-Slip Motion of the Wigner Solid on Liquid Helium. AB - We present time-resolved transport measurements of a Wigner solid (WS) on the surface of liquid helium confined in a micron-scale channel. At rest, the WS is "dressed" by a cloud of quantized capillary waves (ripplons). Under a driving force, we find that repeated WS-ripplon decoupling leads to stick-slip current oscillations, the frequency of which can be tuned by adjusting the temperature, pressing electric field, or electron density. The WS on liquid He is a promising system for the study of polaronlike decoupling dynamics. PMID- 27258880 TI - Tunable Bloch Wave Resonances and Bloch Gaps in Uniform Materials with Reconfigurable Boundary Profiles. AB - We study wave propagation in uniform materials with periodic boundary profiles and introduce for the first time Bloch resonances and Bloch gaps. Bloch resonances are due to transverse phase matching, i.e., the coupling of two transverse standing waves corresponding to different harmonics. These are distinct from well-known Bragg resonances that result from longitudinal phase matching. We show that Bloch gaps can be engineered over the entire first Brillouin zone up to an infinite wavelength, i.e., k_{x}=0, where k_{x} is the wave number in the direction of propagation. This is in contrast to Bragg gaps that open at a fixed wavelength, twice the period of the structure. Bloch resonances and gaps can be tuned by reconfiguring the boundary profile and we derive analytical expressions that predict these phenomena when the amplitude of the profile is small. The theory is fundamental as it broadly applies to wave phenomena that span the quantum to continuum scale with applications that range from condensed matter to acoustics. We validate the theory experimentally for the electromagnetic field at GHz frequencies. We also discuss potential photonic and electronic applications of the theory such as a white-light distributed feedback laser and a two-dimensional electron gas transistor. PMID- 27258881 TI - Multiferroic Two-Dimensional Materials. AB - The relation between unusual Mexican-hat band dispersion, ferromagnetism, and ferroelasticity is investigated using a combination of analytical, first principles, and phenomenological methods. The class of material with Mexican-hat band edge is studied using the alpha-SnO monolayer as a prototype. Such a band edge causes a van Hove singularity diverging with 1/sqrt[E], and a charge doping in these bands can lead to time-reversal symmetry breaking. Herein, we show that a material with Mexican-hat band dispersion, alpha-SnO, can be ferroelastic or paraelastic depending on the number of layers. Also, an unexpected multiferroic phase is obtained in a range of hole density for which the material presents ferromagnetism and ferroelasticity simultaneously. PMID- 27258882 TI - Parity-Time Synthetic Phononic Media. AB - Classical systems containing cleverly devised combinations of loss and gain elements constitute extremely rich building units that can mimic non-Hermitian properties, which conventionally are attainable in quantum mechanics only. Parity time (PT) symmetric media, also referred to as synthetic media, have been devised in many optical systems with the ground breaking potential to create nonreciprocal structures and one-way cloaks of invisibility. Here we demonstrate a feasible approach for the case of sound where the most important ingredients within synthetic materials, loss and gain, are achieved through electrically biased piezoelectric semiconductors. We study first how wave attenuation and amplification can be tuned, and when combined, can give rise to a phononic PT synthetic media with unidirectional suppressed reflectance, a feature directly applicable to evading sonar detection. PMID- 27258883 TI - Emergence of Long-Range Order in BaTiO_{3} from Local Symmetry-Breaking Distortions. AB - By using a symmetry motivated basis to evaluate local distortions against pair distribution function data, we show without prior bias, that the off-center Ti displacements in the archetypal ferroelectric BaTiO_{3} are zone centered and rhombohedral-like across its known ferroelectric and paraelectric phases. We construct a simple Monte Carlo model that captures our main experimental findings and demonstrate how the rich crystallographic phase diagram of BaTiO_{3} emerges from correlations of local symmetry-breaking distortions alone. Our results strongly support the order-disorder picture for these phase transitions, but can also be reconciled with the soft-mode theory of BaTiO_{3} that is supported by some spectroscopic techniques. PMID- 27258884 TI - Terahertz Antiferromagnetic Spin Hall Nano-Oscillator. AB - We consider the current-induced dynamics of insulating antiferromagnets in a spin Hall geometry. Sufficiently large in-plane currents perpendicular to the Neel order trigger spontaneous oscillations at frequencies between the acoustic and the optical eigenmodes. The direction of the driving current determines the chirality of the excitation. When the current exceeds a threshold, the combined effect of spin pumping and current-induced torques introduces a dynamic feedback that sustains steady-state oscillations with amplitudes controllable via the applied current. The ac voltage output is calculated numerically as a function of the dc current input for different feedback strengths. Our findings open a route towards terahertz antiferromagnetic spin-torque oscillators. PMID- 27258885 TI - Hiding in Plain View: Colloidal Self-Assembly from Polydisperse Populations. AB - We report small-angle x-ray scattering experiments on aqueous dispersions of colloidal silica with a broad monomodal size distribution (polydispersity, 14%; size, 8 nm). Over a range of volume fractions, the silica particles segregate to build first one, then two distinct sets of colloidal crystals. These dispersions thus demonstrate fractional crystallization and multiple-phase (bcc, Laves AB_{2}, liquid) coexistence. Their remarkable ability to build complex crystal structures from a polydisperse population originates from the intermediate-range nature of interparticle forces, and it suggests routes for designing self assembling colloidal crystals from the bottom up. PMID- 27258886 TI - Elasticity Dominated Surface Segregation of Small Molecules in Polymer Mixtures. AB - We study the phenomenon of migration of the small molecular weight component of a binary polymer mixture to the free surface using mean field and self-consistent field theories. By proposing a free energy functional that incorporates polymer matrix elasticity explicitly, we compute the migrant volume fraction and show that it decreases significantly as the sample rigidity is increased. A wetting transition, observed for high values of the miscibility parameter can be prevented by increasing the matrix rigidity. Estimated values of the bulk modulus suggest that the effect should be observable experimentally for rubberlike materials. This provides a simple way of controlling surface migration in polymer mixtures and can play an important role in industrial formulations, where surface migration often leads to decreased product functionality. PMID- 27258887 TI - Clustering Implies Geometry in Networks. AB - Network models with latent geometry have been used successfully in many applications in network science and other disciplines, yet it is usually impossible to tell if a given real network is geometric, meaning if it is a typical element in an ensemble of random geometric graphs. Here we identify structural properties of networks that guarantee that random graphs having these properties are geometric. Specifically we show that random graphs in which expected degree and clustering of every node are fixed to some constants are equivalent to random geometric graphs on the real line, if clustering is sufficiently strong. Large numbers of triangles, homogeneously distributed across all nodes as in real networks, are thus a consequence of network geometricity. The methods we use to prove this are quite general and applicable to other network ensembles, geometric or not, and to certain problems in quantum gravity. PMID- 27258888 TI - Electromechanical Interplay in Deformable Dielectric Elastomer Networks. AB - A systematic, statistical-mechanics-based analysis of the response of dielectric elastomers to coupled electromechanical loading is conducted, starting from the monomer level through the polymer chain and ending with closed-form expressions for the polarization and stress fields. It is found that the apparent response at the macrolevel is dictated by four microscopic parameters-the monomer type and polarizability and the chain length and density. Our analysis further reveals a new electrostrictive effect that either reinforces or opposes the polarization induced deformation. The validity of the results is attested through comparisons with well-established experimental measurements of both the polarization field and the electrostrictive stress. PMID- 27258889 TI - Comment on "Testing Planck-Scale Gravity with Accelerators". PMID- 27258890 TI - Erratum: Random Field Driven Spatial Complexity at the Mott Transition in VO_{2} [Phys. Rev. Lett. 116, 036401 (2016)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.116.036401. PMID- 27258891 TI - Publisher's Note: Enhanced Tunneling Electroresistance in Ferroelectric Tunnel Junctions due to the Reversible Metallization of the Barrier [Phys. Rev. Lett. 116, 197602 (2016)]. AB - This corrects the article DOI: 10.1103/PhysRevLett.116.197602. PMID- 27258892 TI - Association of MHC region SNPs with irritant susceptibility in healthcare workers. AB - Irritant contact dermatitis is the most common work-related skin disease, especially affecting workers in "wet-work" occupations. This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) and skin irritant response in a group of healthcare workers. 585 volunteer healthcare workers were genotyped for MHC SNPs and patch tested with three different irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH) and benzalkonium chloride (BKC). Genotyping was performed using Illumina Goldengate MHC panels. A number of SNPs within the MHC Class I (OR2B3, TRIM31, TRIM10, TRIM40 and IER3), Class II (HLA-DPA1, HLA-DPB1) and Class III (C2) genes were associated (p < 0.001) with skin response to tested irritants in different genetic models. Linkage disequilibrium patterns and functional annotations identified two SNPs in the TRIM40 (rs1573298) and HLA-DPB1 (rs9277554) genes, with a potential impact on gene regulation. In addition, SNPs in PSMB9 (rs10046277 and ITPR3 (rs499384) were associated with hand dermatitis. The results are of interest as they demonstrate that genetic variations in inflammation-related genes within the MHC can influence chemical-induced skin irritation and may explain the connection between inflamed skin and propensity to subsequent allergic contact sensitization. PMID- 27258897 TI - Identification of androgen receptor antagonists: In vitro investigation and classification methodology for flavonoid. AB - A tremendous gap exists between the number of potential endocrine disrupting chemicals (EDCs) possibly in the environment and the limitation of traditional regulatory testing. In this study, the anti-androgenic potencies of 21 flavonoids were analyzed in vitro, and another 32 flavonoids from the literature were selected as additional chemicals. Molecular dynamic simulations were employed to obtain four different separation approaches based on the different behaviors of ligands and receptors during the process of interaction. Specifically, ligand receptor complex which highlighted the discriminating features of ligand escape or retention via "mousetrap" mechanism, hydrogen bonds formed during simulation times, ligand stability and the stability of the helix-12 of the receptor were investigated. Together, a methodology was generated that 87.5% of flavonoids could be discriminated as active versus inactive antagonists, and over 90% inactive antagonists could be filtered out before QSAR study. This methodology could be used as a "proof of concept" to identify inactive anti-androgenic flavonoids, as well could be beneficial for rapid risk assessment and regulation of multiple new chemicals for androgenicity. PMID- 27258898 TI - Monitoring dihydrodiol polyaromatic hydrocarbon metabolites produced by the freshwater microalgae Selenastrum capricornutum. AB - We found that microalgae exposed to a mixture of polycyclic aromatic hydrocarbons (PAHs) did not show growth inhibition. Thus, we assumed that they could metabolize these compounds. In this study, the dihydrodiol-type PAH metabolites of benzo(a)pyrene (BaP), benzo(a)anthracene (BaA), benzo(b)fluoranthene (BbF) and benzo(k)fluoranthene (BkF) produced by the freshwater microalgae Selenastrum capricornutum were monitored and quantified using high-performance liquid chromatography with fluorescence detection (HPLC-FD) techniques. Exposure bioassays with S. capricornutum were performed using a 266 ng mL(-1) mixture of PAHs at different exposure times (0.75, 1, 3, 8, 16, 24 and 48 h) under controlled temperature (25 degrees C); the dihydrodiol metabolites formed in the liquid medium and the biomass were quantified. Metabolite identities were confirmed using HPLC-mass spectrometry; most of the metabolites formed were derived from BaA degradation. At 48 h after exposure 5,6-dBaA and 8,9-dBaA/10,11 dBaA were present in the liquid medium at 20% and 67% of the initial mass of BaA, respectively. Three metabolites of BaP were monitored in the liquid medium and biomass and, at 24 h, 4,5-dBaP accounted for 19%; , 7,8-dBaP, 5%; and 9,10-dBaP, 5% relative to the initial BaP mass. Microalgae exposed to BbF showed the presence of 1,2-dBbF and 9,10-dBbF (at 0.3% and 0.1% of the initial BbF mass, respectively) and those exposed to BkF produced 8,9-dBkF (6.5% of the initial BkF mass) in the liquid medium. Seven unknown compounds were formed after exposure; two compounds were identified as the metabolites of BaA and BaP. The results could facilitate the elucidation of the controversial biodegradation mechanism in microalgae. PMID- 27258899 TI - Arsenic entrapment by nanocrystals of Al-magnetite: The role of Al in crystal growth and As retention. AB - The nature of As-Al-Fe co-precipitates aged for 120 days are investigated in detail by High Resolution Transmission Electron Microscopy (HRTEM), Scanning TEM (STEM), electron diffraction, Energy Dispersive X-Ray Spectroscopy (EDS), Electron Energy-Loss Spectroscopy (EELS), and Energy Filtered Transmission Electron Microscopy (EFTEM). The Al present in magnetite is shown to favour As incorporation (up to 1.10 wt%) relative to Al-free magnetite and Al-goethite, but As uptake by Al-magnetite decreases with increasing Al substitution (3.53-11.37 mol% Al). Arsenic-bearing magnetite and goethite mesocrystals (MCs) are formed by oriented aggregation (OA) of primary nanoparticles (NPs). Well-crystalline magnetite likely formed by Otswald ripening was predominant in the Al-free system. The As content in Al-goethite MCs (having approximately 13% substituted Al) was close to the EDS detection limit (0.1 wt% As), but was below detection in Al-goethites with 23.00-32.19 mol% Al. Our results show for the first time the capacity of Al-magnetite to incorporate more As than Al-free magnetite, and the role of Al in favouring OA-based crystal growth under the experimental conditions, and therefore As retention in the formed MCs. The proposed mechanism of As incorporation involves adsorption of As onto the newly formed NPs. Arsenic is then trapped in the MCs as they grow by self-assembly OA upon attachment of the NPs. We conclude that Al may diffuse to the crystal faces with high surface energy to reduce the total energy of the system during the attachment events, thus favouring the oriented aggregation. PMID- 27258900 TI - Modeling study of polychlorinated dibenzo-p-dioxins and dibenzofurans behavior in flue gases under electron beam irradiation. AB - The efficiency of the electron beam treatment of industrial flue gases for the removal of sulfur and nitrogen oxides was investigated as applied to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) using methods of mathematical modeling. The proposed kinetic model of the process includes mechanism of PCDD/Fs decomposition caused by their interaction with OH radicals generated in the flue gases under the electron beam (EB) irradiation as well as PCDD/Fs formation from unburned aromatic compounds. The model allows to predict the main features of the process, which are observed in pilot plant installations, as well as to evaluate the process efficiency. The results of calculations are compared with the available experimental data. PMID- 27258901 TI - Adverse effects and bioconcentration of chromium in two freshwater rotifer species. AB - Bioaccumulation of trivalent (CrIII) and hexavalent chromium (CrVI), and its adverse effects were studied in two rotifer species: Brachionus calyciflorus (two different strains), and Lecane quadridentata. Median Lethal Concentration (LC50) at 24 h of both species showed that CrVI is highly toxic: LC50 ranges from 4.7 * 10(-5) to 4 * 10(-6) mg L(-1)), compared with CrIII: LC50 ranges from 0.64 to 1.279 mg L(-1). Using the LC50 as an exposure concentration, and using atomic absorption, the bioconcentration factor (BCF) was obtained and BCFs of rotifers exposed to CrIII are four orders of magnitude lower than BCFs of rotifers exposed to CrVI. The effect of Cr on the elemental composition of the two species of rotifers in their structures by X-ray microanalysis by energy dispersion showed that Cr is found in intoxicated rotifers, but not in control rotifers. The basal immunoreactivity to metallothioneins is greater in B. calyciflorus than L. quadridentata. The immunoreactivity to metallothioneins decreases in B. calyciflorus when is exposed to CrIII, in contrast in L. quadridentata the immunoreactivity to metallothioneins increase when is exposed to CrIII, and the immunoreactivity to CrVI in L. quadridentata decrease. A mechanism is proposed in which the harder lorica of L. quadridentata acts as a barrier and accumulator of CrVI, and allows for attenuating responses like metallothionein production in L. quadridentata. Instead, in B. calyciflorus the lack of a harder lorica allows for deeper penetration of CrVI, and no time to produce attenuating measures. PMID- 27258902 TI - A comparison of fresh and used aircraft oil for the identification of toxic substances linked to aerotoxic syndrome. AB - Fresh and used aircraft engine lubricants (Mobil Jet Oil II) were analysed using a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTICRMS) and comprehensive two dimensional gas chromatography with high resolution time of flight mass spectrometry (GCxGC-HRTOFMS). The composition of the fresh oil was established, with special focus to its tricresyl phosphate (TCP) content as this has formed the focus for most investigations into aerotoxic syndrome. The results showed that only four TCP isomers were present at detectable levels in the fresh oil: mmm-TCP, mmp-TCP, ppm-TCP and ppp-TCP. The results indicate that the formulation of Mobile Jet Oil II does not contain the more toxic ortho substituted TCP isomers at concentrations above 0.0005%. The temperatures of jet engines during operation are greater than 200 degrees C which creates the potential to alter the composition of the original oil and create other toxic compounds. The results show there may be a significant risk from alkylated cresyl phosphates, which were identified in the used oils at concentrations calculated in the range of 0.13-0.69%. w/w. Several xylenyl and ethylphenyl phosphates have been shown to exhibit a similar toxicity to ortho substituted TCP isomers which makes there discovery in used oil significant. These compounds should be included in future aircraft air quality studies and when assessing the risks and causes of aerotoxic syndrome. PMID- 27258903 TI - Evaluating the mutagenicity of the water-soluble fraction of air particulate matter: A comparison of two extraction strategies. AB - Many studies have focused on assessing the genotoxic potential of the organic fraction of airborne particulate matter. However, the determination of water soluble compounds, and the evaluation of the toxic effects of these elements can also provide valuable information for the development of novel strategies to control atmospheric air pollution. To determine an appropriate extraction method for assessing the mutagenicity of the water-soluble fraction of PM, we performed microwave assisted (MW) and ultrasonic bath (US) extractions, using water as solvent, in eight different air samples (TSP and PM10). Mutagenicity and extraction performances were evaluated using the Salmonella/microsome assay with strains TA98 and TA100, followed by chemical determination of water-soluble metals. Additionally, we evaluated the chemical and biological stability of the extracts testing their mutagenic potential and chemically determining elements present in the samples along several periods after extraction. Reference material SRM 1648a was used. The comparison of MW and US extractions did not show differences on the metals concentrations, however positive mutagenic responses were detected with TA98 strain in all samples extracted using the MW method, but not with the US bath extraction. The recovery, using reference material was better in samples extracted with MW. We concluded that the MW extraction is more efficient to assess the mutagenic activity of the soluble fraction of airborne PM. We also observed that the extract freezing and storage over 60 days has a significant effect on the mutagenic and analytical results on PM samples, and should be avoided. PMID- 27258904 TI - A Non-perturbing Probe of Coiled Coil Formation Based on Electron Transfer Mediated Fluorescence Quenching. AB - Coiled coils are abundant in nature, occurring in ~3% of proteins across sequenced genomes, and are found in proteins ranging from transcription factors to structural proteins. The motif continues to be an important model system for understanding protein-protein interactions and is finding increased use in bioinspired materials and synthetic biology. Knowledge of the thermodynamics of self-assembly, particularly the dissociation constant KD, is essential for the application of designed coiled coils and for understanding the in vivo specificity of natural coiled coils. Standard methods for measuring KD typically rely on concentration dependent circular dichroism (CD). Fluorescence methods are an attractive alternative; however Trp is rarely found in an interior position of a coiled coil, and appending unnatural fluorophores can perturb the system. We demonstrate a simple, non-perturbing method to monitor coiled coil formation using p-cyanophenylalanine (FCN) and selenomethionine (MSe), the Se analogue of Met. FCN fluorescence can be selectively excited and is effectively quenched by electron transfer with MSe. Both FCN and MSe represent minimally perturbing substitutions in coiled coils. MSe quenching of FCN fluorescence is shown to offer a non-perturbing method for following coiled coil formation and for accurately determining dissociation constants. The method is validated using a designed heterodimeric coiled coil. The KD deduced by fluorescence monitored titration is in excellent agreement with the value deduced from concentration dependent CD measurements to within the uncertainty of the measurement. However, the fluorescence approach requires less protein, is less time-consuming, can be applied to lower concentrations and could be applied to high throughput screens. PMID- 27258905 TI - Narrative review of strategies by organizations for building evaluation capacity. AB - Program evaluation is an important source of information to assist organizations to make "evidence-informed" decisions about program planning and development. The objectives of this study were to identify evaluated strategies used by organizations and program developers to build the program evaluation capacity of their workforce, and to describe success factors and lessons learned. Common elements for successful evaluation capacity building (ECB) include: a tailored strategy based on needs assessment, an organizational commitment to evaluation and ECB, experiential learning, training with a practical element, and some form of ongoing technical support within the workplace. ECB is a relatively new field of endeavor, and, while existing studies in ECB are characterized by lower levels of evidence, they suggest the most successful approaches to ECB are likely to be multifaceted. To build the level of evidence in this field, more rigorous study designs need to be implemented in the future. PMID- 27258907 TI - Sensitive Room Temperature Photoluminescence-Based Sensing of H2S with Novel CuO ZnO Nanorods. AB - Novel CuO nanoparticle-capped ZnO nanorods have been produced using a pulsed laser deposition (PLD) method. These nanorods are shown to grow by a CuO nanoparticle-assisted vapor-solid-solid (V-S-S) mechanism. The photoluminescence (PL) accompanying ultraviolet illumination of these capped nanorod samples shows large variations upon exposure to trace quantities of H2S gas. The present data suggest that both the Cu-doped ZnO stem and the CuO capping nanoparticle contribute to optical H2S sensing with these CuO-ZnO nanorods. This study represents the first demonstration of PL-based H2S gas sensing, at room temperature, with sub-ppm sensitivity. It also opens the way to producing CuO-ZnO nanorods by a V-S-S mechanism using gas-phase methods other than PLD. PMID- 27258906 TI - Deregulation of the HOXA9/MEIS1 axis in acute leukemia. AB - PURPOSE OF REVIEW: HOXA9 is a homeodomain transcription factor that plays an essential role in normal hematopoiesis and acute leukemia, in which its overexpression is strongly correlated with poor prognosis. The present review highlights recent advances in the understanding of genetic alterations leading to deregulation of HOXA9 and the downstream mechanisms of HOXA9-mediated transformation. RECENT FINDINGS: A variety of genetic alterations including MLL translocations, NUP98-fusions, NPM1 mutations, CDX deregulation, and MOZ-fusions lead to high-level HOXA9 expression in acute leukemias. The mechanisms resulting in HOXA9 overexpression are beginning to be defined and represent attractive therapeutic targets. Small molecules targeting MLL-fusion protein complex members, such as DOT1L and menin, have shown promising results in animal models, and a DOT1L inhibitor is currently being tested in clinical trials. Essential HOXA9 cofactors and collaborators are also being identified, including transcription factors PU.1 and C/EBPalpha, which are required for HOXA9-driven leukemia. HOXA9 targets including IGF1, CDX4, INK4A/INK4B/ARF, mir-21, and mir 196b and many others provide another avenue for potential drug development. SUMMARY: HOXA9 deregulation underlies a large subset of aggressive acute leukemias. Understanding the mechanisms regulating the expression and activity of HOXA9, along with its critical downstream targets, shows promise for the development of more selective and effective leukemia therapies. PMID- 27258908 TI - Consequences of Lost Gallstones During Laparoscopic Cholecystectomy: A Review Article. AB - BACKGROUND: Laparoscopic cholecystectomy (LC) has become a popular and widespread procedure for the treatment of gallstone disease. There is still an increasing concern about specific complications of LC due to gallbladder perforation and spillage of bile and stones. Although unretrieved intraperitoneal gallstones rarely become symptomatic, their infective complications may cause serious morbidities even after a long interval from LC. METHODS: We performed a review of the literature on the diagnosis, prevention, consequences, and management of lost gallstones. All studies with a focus on lost gallstones or perforated gallbladder were analyzed to evaluate the postoperative complications. RESULTS: Between 1991 and 2015, >250 cases of postoperative complications of spilled gallstones were reviewed in the surgical literature. The most common complications are intraperitoneal abscesses and fistulas. Confusing clinical pictures due to gallstones spreading in different locations makes diagnosis challenging. Even asymptomatic dropped gallstones may masquerade intraperitoneal neoplastic lesions. CONCLUSIONS: Every effort should be made to prevent gallbladder perforation; otherwise, they should be retrieved immediately during laparoscopy. In cases with multiple large spilled stones or infected bile, conversion to open surgery can be considered. Documentation in operative notes and awareness of patients about lost gallstones are mandatory to early recognition and treatment of any complications. PMID- 27258909 TI - Late Postoperative Complications in Laparoscopic Sleeve Gastrectomy (LVSG) Versus Laparoscopic Roux-en-y Gastric Bypass (LRYGB): Meta-analysis and Systematic Review. AB - AIMS AND OBJECTIVES: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic vertical sleeve gastrectomy (LVSG), have been proposed as cost effective strategies to manage obesity-related chronic disease. The objectives of this meta-analysis and systematic review were to analyze the "late postoperative complication rate (>30 days)" for these 2 procedures. MATERIALS AND METHODS: Randomized controlled trials (RCTs) published between 2000 and 2015 comparing the late complication rates, that is, >30 days following LVSG and LRYGB in adult population (ie, 16 y and above) were selected from PubMed, Medline, Embase, Science Citation Index, Current Contents, and the Cochrane database. The outcome variables analyzed included mortality rate, major and minor complications, and interventions required for their management and readmission rates. Random effects model was used to calculate the effect size of both binary and continuous data. Heterogeneity among the outcome variables of these trials was determined by the Cochran Q statistic and I index. The meta-analysis was prepared in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analyses guidelines. RESULTS: Six RCTs involving a total of 685 patients (LVSG, n=345; LRYGB, n=340) reported late major complications. A nonstatistical reduction in relative odds favoring the LVSG procedure was observed [odds ratio (OR), 0.64; 95% confidence interval (CI), 0.21-1.97; P=0.4]. Four RCTs representing 408 patients (LVSG, n=208; LRYGB, n=200) reported late minor complications. A nonstatistically significant reduction of 36% in relative odds favoring the LVSG procedure was observed (OR, 0.64; 95% CI, 0.28-1.47; P=0.3). A 37% relative reduction in odds was observed in favor of the LVSG for the need for additional interventions to manage late postoperative complications that did not reach statistical significance (OR, 0.63; 95% CI, 0.19-2.05; P=0.4). No study specifically reported readmissions required for the management of late complication. CONCLUSIONS: This meta-analysis and systematic review of RCTs shows that the development of late (major and minor) complications is similar between LVSG and LRYGB procedures, 6 months to 3 years postoperatively, and they do not lead to higher readmission rate or reoperation rate for either procedure. However longer-term surveillance is required to accurately describe the patterns of late complications in these patients. PMID- 27258910 TI - Laparoscopic Sleeve Gastrectomy and Nutrient Deficiencies: A Prospective Study. AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is being increasingly established as a definitive procedure for weight loss. The mechanism for weight loss in LSG is gastric restriction and neurohormonal changes, but there is deficient information on its nutritional effect. The aim of this prospective study was to assess vitamin and micronutrient deficiencies following LSG (whats and when) in organized follow-up visits. PATIENTS AND METHODS: LSG was performed in 112 consecutive patients between June 2010 and December 2013. In all patients, the vitamin and micronutrient deficiencies were corrected before the LSG procedure. Patients were investigated for vitamin and micronutrient concentrations 2, 4, 6, 9, and 12 months after surgery. RESULTS: During the study time, 112 patients (65% female) underwent LSG. The mean age was 26 years (range: 20 to 37 y), and the mean preoperative body mass index was 41 (range: 35 to 52). Complications and nutrient deficiencies were observed and analyzed throughout the follow-up period. CONCLUSIONS: The appearance of vitamin and nutritional deficiencies after LSG is a common phenomenon. Correction of the deficiencies before surgery, sufficient supplementation immediately after the procedure, and routine long follow-up are important to avoid the serious consequences of the deficiencies. PMID- 27258911 TI - Long-term Effect of Percutaneous Electrical Neurostimulation of Dermatome T6 for Appetite Reduction and Weight Loss in Obese Patients. AB - INTRODUCTION: A continuous feeling of hunger is the major cause of dietary treatment failure and the patients abandon the diet. A previous study of our group demonstrated that percutaneous electrical neurostimulation (PENS) of T6 dermatome induces an appetite reduction and significantly greater weight loss compared with only diet as a preoperative measure in morbidly obese patients who are candidates for bariatric surgery. The aim of this study was to evaluate the long-term effect of this therapy. PATIENTS AND METHODS: A prospective study was performed, including obese patients with a body mass index between 30 and 40 kg/m undergoing PENS of dermatome T6. Weight loss, dietary compliance, and appetite were assessed before the treatment, after 12 weeks of treatment, and 3 and 9 months after completing the therapy. RESULTS: A total of 150 patients were included in the study. A mean weight loss of 11.8+/-2.6 kg was obtained after 12 weeks of treatment. Three months after completing the therapy, mean weight loss was 14.6+/-2.7 kg and 9 months after completing the treatment mean weight loss was 14.5+/-2.8 kg. Median appetite perception quantified by Visual Analogue Scale was 6 before the treatment, 1 after completing the treatment, 1 at 3 months after completing the treatment, and 4 at 9 months after completing the treatment. Dietary compliance after 12 weeks of treatment was 90%, 84% at 3 months after completing the treatment, and 62% at 9 months after completing the treatment. CONCLUSION: PENS of dermatome T6 achieves a significant appetite reduction, which is maintained 3 months after completing the therapy. Later, the patients' appetite is restored, but they do not regain the weight lost. PMID- 27258912 TI - The Effect of Equal Ratio Ventilation on Oxygenation, Respiratory Mechanics, and Cerebral Perfusion Pressure During Laparoscopy in the Trendelenburg Position. AB - The aim of this study was to investigate the effects of equal ratio ventilation (ERV) on oxygenation, respiratory mechanics, and the cerebral perfusion pressure during pneumoperitoneum in the Trendelenburg position. Thirty patients undergoing laparoscopic low anterior resection (25 to 65 y) were enrolled. Mechanical ventilator was set to volume-controlled mode at an inspiratory to expiratory (I:E) ratio of 1:2 with a tidal volume of 8 mL/kg of ideal body weight with a 5 cm H2O positive end-expiratory pressure. Twenty minutes after pneumoperitoneum in the Trendelenburg position, the I:E ratio was changed to 1:1 for 20 minutes and then restored to 1:2. No significant changes in arterial oxygen tension and respiratory compliance after adopting ERV. Mean arterial pressure and cerebral perfusion pressure decreased significantly over time after adopting the Trendelenburg position during pneumoperitoneum (P=0.014 and 0.005, respectively). In conclusion, there was no improvement in oxygenation or respiratory mechanics with ERV. PMID- 27258913 TI - Preoperative Very Low-Calorie Diet Reduces Technical Difficulty During Laparoscopic Cholecystectomy in Obese Patients. AB - This study investigates the effectiveness of preoperative very low-calorie diet (VLCD) in laparoscopic cholecystectomy. A prospective observational study of consecutive patients undergoing laparoscopic cholecystectomy was undertaken. At the preoperative visit, all patients were advised to adhere to VLCD for 2 weeks before surgery (<800 kcal/d). Patients were judged to have complied with the VLCD if weight loss >2 kg. Technical difficulty was assessed using questionnaires. A total of 38 patients met the inclusion criteria. Difficulty of visualization and dissection of Calot's triangle in obese patients was twice that of nonobese patients (P=0.01). In 62% of procedures involving obese VLCD noncompliant patients, the surgeon experienced >=1 area of technical difficulty, compared with 0% of procedures on obese, compliant patients (P=0.018). Difficulty of dissection of the gallbladder bed was 3 times higher in obese, noncompliant patients, compared with obese, compliant patients (P=0.07). Adherence to a 2-week preoperative VLCD may reduce technical difficulty of laparoscopic cholecystectomy in obese patients. PMID- 27258914 TI - Case-matched Comparison of Robotic Versus Laparoscopic Proctectomy for Inflammatory Bowel Disease. AB - The present study reports an early institutional experience with robotic proctectomy (RP) and outcome comparison with laparoscopic proctectomy (LP) in patients with inflammatory bowel disease (IBD). Patients who underwent either RP or LP during proctocolectomy for IBD between January 2010 and June 2014 were matched (1:1) and reviewed. Twenty-one patients undergoing RP fulfilled the study criteria and were matched with an equal number of patients who had LP. Operative time was longer (304 vs. 213 min, P=0.008) and estimated blood loss was higher in the RP group (360 vs. 188 mL, P=0.002). Conversion rates (9.5% vs. 14.3%, P>0.99), time to first bowel movement(2.29+/-1.53 vs. 2.79+/-2.26, P=0.620), and hospital length stay(7.85+/-6.41 vs. 9.19+/-7.47 d, P=0.390) were similar in both groups. No difference was noted in postoperative complications, ileal pouch to anal canal anastomosis-related outcomes, Cleveland Global Quality of Life, and Short Form-12 health survey outcomes between RP and LP. Our good results with standard laparoscopy are unlikely to be improved with robotics in proctectomy cases. Potential benefits of robotic approach for completion proctectomy warrant further investigation as experience grows with robotics. PMID- 27258915 TI - Learning Curve for Laparoscopic Major Hepatectomy: Use of the Cumulative Sum Method. AB - BACKGROUND: Laparoscopic liver resection (LLR) has now become a worldwide practice. However, the adoption of laparoscopic major hepatectomy (LMH) was slow. We report our center's experience in laparoscopic major resections. METHOD: A total of 156 LLRs from 2002 to 2014 were studied. The clinical parameters of LMHs were compared with those of minor resections. The learning curve of LMHs was investigated using the cumulative sum (CUSUM) analysis of operative time. Subgroup analysis of right posterior sectionectomies against anterolateral hepatectomies was conducted. RESULTS: Among the 156 LLRs, 49 (31%) were LMHs. CUSUM analysis showed that operative time improved after the 25th LMH. Beyond that proportion of pure laparoscopic LMHs increased (18/25 vs. 24/24, P=0.005); Pringle maneuver was not required (4/25 vs. 0/24, P=0.041). Blood loss (800 vs. 500 mL, P=0.034) and transfusion rate (13/25 to 3/24, P=0.003) improved in latter LMHs. Right posterior sectionectomies had significantly more blood loss than anterolateral LMHs (500 vs. 1500 mL, P=0.034). CONCLUSION: Laparoscopic major resection is safe and feasible; operative outcomes improved after overcoming the learning curve. Right posterior sectionectomy, however, should be further evaluated for its cost-effectiveness. PMID- 27258916 TI - Transanal Endoscopic Microsurgery: Current and Future Perspectives. AB - Transanal endoscopic microsurgery is part of the colorectal surgeons' armamentarium for over 2 decades. Since its first implementation for the resection of benign and T1 malignant lesions in the rectum several new indications were developed and it carries additional promise for further extension in upcoming years. Herein we review the technique, its current indications, novel implications, and future perspectives. PMID- 27258917 TI - Outcomes From an Enhanced Recovery Program for Laparoscopic Gastric Surgery. AB - PURPOSE: To examine the outcomes from an enhanced recovery after surgery (ERAS) program for laparoscopic gastric surgery. MATERIALS AND METHODS: This was a prospective study of patients undergoing elective laparoscopic gastric resection in an ERAS protocol at a single institution between 2008 and 2012. Outcomes included the length of hospital stay, intraoperative and postoperative complications, the readmission rate, the reoperation rate, and the 30-day mortality. RESULTS: Of the 86 patients, 60 underwent partial gastrectomy and 26 underwent total gastrectomy. Median lymph nodes sampled was 15 (range, 9 to 47). The median length of hospital stay was 4 (range, 1 to 44) days. The conversion rate to open surgery was 11.6%. Four patients (4.7%) had an anastomotic leak. Three patients had postoperative bleeding (4.7%). About 4.7% (n=4) of the patients required readmission and 8.1% required reoperation (n=7). The 30-day mortality rate was 2.3% (n=2) due to complications from anastomotic leak. CONCLUSIONS: Laparoscopic gastrectomy within an ERAS protocol results in a short hospital stay with an acceptable morbidity and mortality rate. PMID- 27258918 TI - Open Versus Laparoscopic Surgery for Rectal Cancer: Single-Center Results of 587 Cases. AB - PURPOSE: We aimed to compare the short-term and long-term results of laparoscopic and open rectal resections. METHODS: A total of 587 rectal cancer patients were included. The main measures were demographic data, duration of surgery, early postoperative results, pathologic data, and long-term follow-up. RESULTS: There were no significant differences in demographic data, morbidity rate, tumor location, and sphincter-preservation rates between the 2 groups. The duration of surgery (155 vs. 173 min, P<0.001), time to gas passage, defecation, and solid food intake and length of hospital stay were significantly shorter in the laparoscopic group than the open group (P<0.05). According to the univariate and multivariate analysis, laparoscopic surgery did not have an effect on local recurrence but had a favorable effect on survival rates. CONCLUSIONS: Laparoscopic rectal surgery has advantages over open surgery with respect to short-term and long-term clinical results and when performed in high-volume centers. PMID- 27258919 TI - Laparoscopic Liver Resection can be an Effective Way in Obese Patients: A Single Center of 2-Year Experience. AB - OBJECTIVE: To evaluate the feasibility and safety of laparoscopic liver resection in obese patients, we compared the operative outcomes between obese and nonobese patients, also between laparoscopic liver resection and open liver resection of obese and nonobese patients. MATERIALS AND METHODS: A total of 86 patients suffering from liver resection in our department from January 2013 to December 2014 were divided into 3 groups: the obese patients group for laparoscopic liver resection, the nonobese patients group for laparoscopic liver resection and the obese patients group for open liver resection. Characteristics and clinic data of 3 groups were studied. RESULTS: Characteristics of patients and clinic data were equivalent between the 3 groups. The groups were well matched in age, sex distribution, and liver function (P>0.05). There were no significant differences in the operative time, estimated blood loss, time to oral intake, and postoperative hospital stay in the 3 groups. Tumor diameter of laparoscopic liver resection groups in obese patients was smaller than open liver resections groups in obese patients (P<0.05), but there were no obvious difference of tumor diameter in the laparoscopic liver resection groups of the obese patients and the nonobese patients. CONCLUSIONS: Obesity should not be seen as a contraindication for laparoscopic liver resection, which is a safe and feasible procedure for obese patients. PMID- 27258920 TI - Willems I VS Willems II: A comparative study of accuracy in 5-15 year old Indian children. AB - BACKGROUND: Studies testing the Willems method of age estimation with gender specific scores on different population groups have reported consistently more accurate results over other methods. Not enough is known about the validity of Willems non-gender specific scores. AIM: The present study aimed to compare the accuracy of the Willems I (gender-specific scores) and Willems II methods (non gender-specific scores) in the age estimation of 5-15 year-old Indian children. DESIGN: In this cross-sectional observational study, the Willems I and II methods were tested and compared for accuracy in estimating the age of 1200 Indian children aged 5-15 years. RESULTS: The mean differences between dental age calculated by the Willems I method and chronological age were +0.09+/-0.80 years, +0.08+/-0.80 years and +0.09+/-0.80 years for boys, girls and the total sample, respectively. With the Willems II method, the values were -0.06+/-0.80 years, +0.11+/-0.79 years and +0.01+/-0.80 years for boys, girls and the total sample, respectively. Both methods did not show any statistically significant differences between dental and chronological ages for either gender or the total sample (p>0.05). CONCLUSION: The Willems I method was more accurate in predicting age of boys, while the Willems II method was more accurate in girls in the present study, but not significantly so. Both methods are appropriate for use in this population. PMID- 27258922 TI - 13,14-seco-Withanolides from Physalis minima with Potential Anti-inflammatory Activity. AB - Four new 13,14-seco-withanolides, minisecolides A - D (1 - 4), together with three known analogues 5 - 7, were isolated from the whole plants of Physalis minima. The structures of new compounds were determined on the basis of spectroscopic analysis, including (1) H-, (13) C-NMR, 2D-NMR (HMBC, HSQC, ROESY), and HR-ESI-MS. Evaluation of all isolates for their inhibitory effects on nitric oxide (NO) production was conducted on lipopolysaccaride-activated RAW264.7 macrophages. Compounds 2, 3, 5, and 6 showed inhibitory activities, especially for compound 5 with IC50 value of 3.87 MUm. PMID- 27258921 TI - Forensic facial reconstruction: Nasal projection in Brazilian adults. AB - The nose has a marked cognitive influence on facial image; however, it loses its shape during cadaveric decomposition. The known methods of estimating nasal projection using Facial Reconstruction are lacking in practicality and reproducibility. We attempted to relate the points Rhinion, Pronasale and Prosthion by studying the angle formed by straight lines that connect them. Two examiners measured this angle with the help of analysis and image-processing software, Image J, directly from cephalometric radiographs. The sample consisted of 300 males, aged between 24 and 77 years, and 300 females, aged 24 to 69 years. The proposed angle ranged from 80 degrees to 100 degrees in both sexes and all ages. It was considered possible to use a 90 degrees angle from projections of the Rhinion and Prosthion points in order to determine the Pronasale position, as well as to estimate the nasal projection of Brazilian adults. PMID- 27258923 TI - Avian Cephalic Vascular Anatomy, Sites of Thermal Exchange, and the Rete Ophthalmicum. AB - The general anatomy of avian cephalic blood vessels is well known and there are published details of their role in physiological thermoregulation. Unfortunately, the finer details of vascular pathways to and from sites of thermal exchange are not well known. Additionally, the role of the rete ophthalmicum (RO), a vascular heat exchanger in the temporal region, has been investigated in terms of brain temperature regulation, yet only the arteries have received substantial attention. Without anatomical details of both the arterial and venous pathways, the role of blood vessels in physiological thermoregulation is incomplete. Cephalic vascular anatomy of multiple avian taxa was investigated using a differential-contrast, dual-vascular injection technique and high-resolution X ray microcomputed tomography. Sites of thermal exchange (oral, nasal, and orbital regions) and the RO were given special attention due to their known roles in cephalic thermoregulation. Blood vessels to and from sites of thermal exchange were investigated to detect conserved vascular patterns and their ability to deliver cooled blood to the RO and dural venous sinus. Sites of thermal exchange were supplied by arteries directly and through collateral pathways. Veins were found to offer multiple pathways that could influence the temperature of neurosensory tissues, as well as pathways that would bypass neurosensory tissues. These results question the paradigm that arterial blood from the RO is the primary method of brain cooling in birds. A shift in the primary role of the RO from brain cooling to regulating and maintaining the temperature of the avian eye should be further investigated. Anat Rec, 299:1461-1486, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27258925 TI - The effect of parent education program for preschool children with developmental disabilities: A randomized controlled trial. AB - AIM: This study aimed to evaluate the efficacy of a parent education program, the Happy Parenting program, for Chinese preschool children with developmental disabilities. METHODS: This study adopted randomized controlled trial design without blinding. Participants were randomized into intervention group (n=62) who were offered the Happy Parenting program delivered by educational psychologists and trainee educational psychologists, and a control group (n=57) who were offered a parent talk after the intervention group had completed treatment. Parent participants were requested to complete questionnaires on their children's behavior, their parenting stress, and discipline strategies. RESULTS: Analysis was by intention-to-treat. The results indicated significant decrease in child problem behaviors, parenting stress and dysfunctional discipline strategies in the intervention group at post-intervention. CONCLUSION: This study provided promising evidence on the effectiveness of a parent education program, the Happy Parenting program, for Chinese preschool children with developmental disabilities. PMID- 27258924 TI - Examining the cognitive profile of children with Developmental Coordination Disorder. AB - BACKGROUND: While primarily a motor disorder, research considering the cognitive abilities in children with Developmental Coordination Disorder (DCD) is limited; even though these children often struggle academically. AIMS: The present study aimed to characterise the IQ profile of children with and without DCD, and to identify whether children with DCD exhibit specific cognitive weaknesses. METHODS AND PROCEDURES: 104 children participated in the study. Fifty-two children (mean age, 9 years) with a diagnosis of DCD were matched to 52 typically-developing children by age and gender. Cognitive ability was assessed using the Wechsler Intelligence Scale for Children (WISC-IV). OUTCOMES AND RESULTS: Children with DCD performed poorer than their peers on processing speed and working memory measures. Individual analyses revealed varied performance in the DCD group across all cognitive indices, despite displaying Full-Scale IQs in the typical range. Discriminant function analyses show processing speed and working memory performance predicted only 23% of between-group variability. CONCLUSIONS: Children with DCD present with a heterogeneous cognitive profile, lending support to individual case analyses in research and when designing educational assistance plans. The motorically-demanding nature of the WISC-IV processing speed tasks raises specific concerns about using this index of the IQ assessment in this population. Research and practical implications are raised. PMID- 27258926 TI - Dorsal Augmentation-Choosing the Right Material for the Right Patient. PMID- 27258927 TI - Assessment of the Predictive Value of the Modified Frailty Index for Clavien Dindo Grade IV Critical Care Complications in Major Head and Neck Cancer Operations. AB - IMPORTANCE: Functional status and physiologic deficits independent of age are being recognized for surgical risk stratification. Frailty is expressed as a combination of decreased physiologic reserve and multisystem impairments distinct from normal aging processes. OBJECTIVE: To assess the predictive value of the Modified Frailty Index (mFI) for Clavien-Dindo grade IV (CDIV) (intensive care unit-level complications) and grade V (mortality) after major head and neck oncologic surgery. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of prospectively collected American College of Surgeons National Surgical Quality Improvement Program data. All major head and neck cancer operations data were obtained from the January 1, 2006, to December 31, 2013, American College of Surgeons National Surgical Quality Improvement Program databases. Fifteen variables composed a previously validated mFI, with higher mFIs identifying more frail patients. Clavien-Dindo grade IV and mortality were defined using a preexisting mapping scheme from the Canadian Study of Health and Aging. Multivariable logistic regression analyses were performed. MAIN OUTCOMES AND MEASURES: The primary outcome measures were Clavien-Dindo Grade IV critical care complications and Grade V complications (mortality). Second outcomes included morbidity, readmission, and reoperation. RESULTS: There were 1193 major head and neck operations in the American College of Surgeons National Surgical Quality Improvement Program databases, with 86 (7.2%) CDIV complications. The mean (SD) age of all patients was 63.4 (12.4) years, and 67.7% (807 of 1193) were male. Clavien-Dindo grade IV significantly increased from 4.6% (22 of 483) to 100% (1 of 1) from nonfrail to the frailest patients (R2 = 0.79, P < .001). Mortality increased with the mFI (but not significantly) from 0.8% (4 of 483) to 3.6% (2 of 55) (R2 = 0.46, P = .42). Overall morbidity was not significantly associated or correlated with the mFI. On cross tabulation, increases in the mFI led to more CDIV complications in patients undergoing glossectomy (P = .03), mandibulectomy (P = .02), or laryngectomy (P = .002). Patients undergoing pharyngectomy or esophagectomy did not have significant increases in CDIV complications by the mFI. The coefficients of determination for each category were R2 = 0.62 for glossectomy, R2 = 0.72 for mandibulectomy, R2 = 0.97 for laryngectomy, R2 = 0.94 for pharyngectomy, and R2 = 1.00 for esophagectomy. On multivariable analysis, the mFI was associated with CDIV complications (odds ratio, 1.65; 95% CI, 1.15 2.37) but not mortality (odds ratio, 0.78; 95% CI, 0.34-1.76). CONCLUSIONS AND RELEVANCE: The mFI is predictive of postoperative critical care support after surgery for head and neck cancer. Specifically, increases in mFIs were strongly associated with CDIV complications for glossectomy, mandibulectomy, and laryngectomy. Classifying patients by their functional status using the mFI may help predict outcomes after head and neck oncologic surgery. PMID- 27258928 TI - Mysticism and schizophrenia: A phenomenological exploration of the structure of consciousness in the schizophrenia spectrum disorders. AB - Mysticism and schizophrenia are different categories of human existence and experience. Nonetheless, they exhibit important phenomenological affinities, which, however, remain largely unaddressed. In this study, we explore structural analogies between key features of mysticism and major clinical-phenomenological aspects of the schizophrenia spectrum disorders-i.e. attitudes, the nature of experience, and the 'other', mystical or psychotic reality. Not only do these features gravitate around the issue of the basic dimensions of consciousness, they crucially seem to implicate and presuppose a specific alteration of the very structure of consciousness. This finding has bearings for the understanding of consciousness and its psychopathological distortions. PMID- 27258929 TI - Beliefs about hearing voices. AB - People who experience auditory verbal hallucinations (AVHs) vary in whether they believe their AVHs are self-generated or caused by external agents. It remains unclear whether these differences are influenced by the "intensity" of the voices, such as their frequency or volume, or other aspects of their phenomenology. We examined 35 patients with schizophrenia or schizoaffective disorder who experienced AVHs. Patients completed a detailed structured interview about their AVHs, including beliefs about their cause. In response, 20 (57.1%) reported that their AVHs were self-generated, 9 (25.7%) were uncertain, and 6 (17.1%) reported that their AVHs were caused by external agents. Several analytical approaches revealed little or no evidence for associations between either AVH intensity or phenomenology and beliefs about the AVH's cause; the evidence instead favoured the absence of these associations. Beliefs about the cause of AVHs are thus unlikely to be explained solely by the phenomenological qualities of the AVHs. PMID- 27258930 TI - Effect of Cooking on Isoflavones, Phenolic Acids, and Antioxidant Activity in Sprouts of Prosoy Soybean (Glycine max). AB - Soy sprouts possess health benefits and is required to be cooked before consumption. The effects of cooking on the phenolic components and antioxidant properties of soy sprouts with different germination days were investigated. A food-grade cultivar Prosoy with a high protein content was germinated for 1, 2, 3, 5, and 7 d and cooked till palatable for 20, 20, 5, 5, and 7 min, respectively. Total phenolic content (TPC), total flavonoids content (TFC), condensed tannins content (CTC), individual phenolic acids, isoflavones, DPPH, ferric-reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) of raw and cooked sprouts were measured. Cooking caused significant losses in phenolic content and antioxidant activities, and maximum loss was on day 3 > 5 > 7, including TPC (32%, 23%, and 15%), TFC (50%, 44%, and 20%), CTC (73%, 47%, and 12%), DPPH (31%, 15%, and 5%), FRAP (34%, 25%, and 1%), and ORAC (34%, 22%, 32%), respectively. Cooking caused significant losses in most individual phenolic acid, benzoic group, cinnamic group, total phenolic composition, individual isoflavones, and total isoflavones. The losses of phenolic acids such as gallic, protocatechuic, hydroxybenzoic, syringic, chlorogenic, or sinapic acids during cooking were not compensated by the increases in trihydroxybenzoic, vanillic or coumaric acids on certain days of germination. Cooking caused minimal changes in phenolic acid composition of day 1 and 2 sprouts compared to 3, 5, and 7 d sprouts. PMID- 27258931 TI - Effects of the multidrug resistance-1 gene on drug resistance in primary immune thrombocytopenia. AB - Primary immune thrombocytopenia (ITP) is an autoimmune disorder that is characterized by low platelet count. Glucocorticoids (GCs) resistance is a great challenge in the treatment of ITP. P-glycoprotein (P-gp) is a widely studied protein, which is associated with drug resistance. However, in ITP, the functional activity and immune regulation mechanism of P-gp remain uncertain. In this study, we evaluated the expression and functional activity of P-gp in different lymphocyte subsets, explored the correlation between P-gp function and GCs resistance and investigated the role of P-gp in ITP pathogenesis. Results indicated that the functional activity and mRNA level of P-gp were significantly higher in GCs-nonresponsive patients than in GCs-responsive patients with ITP. However, these differences in P-gp were only significant in CD8+ T cells. P-gp function was related to disease activity rather than GCs therapy. P-gp was involved in secreting granzyme B and perforin, maintaining autoreactive lymphocytes survival and enhancing autologous platelets lysis in ITP. In conclusion, over-functional P-gp might play an important role in the pathogenesis of ITP and induce GCs resistance in nonresponsive ITP patients. The blockage of P gp could be a promising therapeutic approach for GCs-resistant patients with ITP. PMID- 27258932 TI - Microstructure and mechanical properties of Ti-15Zr alloy used as dental implant material. AB - Ti-Zr alloys have recently started to receive a considerable amount of attention as promising materials for dental applications. This work compares mechanical properties of a new Ti-15Zr alloy to those of commercially pure titanium Grade4 in two surface conditions - machined and modified by sand-blasting and etching (SLA). As a result of significantly smaller grain size in the initial condition (1-2um), the strength of Ti-15Zr alloy was found to be 10-15% higher than that of Grade4 titanium without reduction in the tensile elongation or compromising the fracture toughness. The fatigue endurance limit of the alloy was increased by around 30% (560MPa vs. 435MPa and 500MPa vs. 380MPa for machined and SLA-treated surfaces, respectively). Additional implant fatigue tests showed enhanced fatigue performance of Ti-15Zr over Ti-Grade4. PMID- 27258933 TI - Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience. AB - INTRODUCTION: The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries. MATERIAL AND METHODS: A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation. RESULTS: Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1:3). CONCLUSIONS: Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures. PMID- 27258934 TI - Pro-cognitive action of CART is mediated via ERK in the hippocampus. AB - Although cocaine- and amphetamine-regulated transcript peptide (CART) is detected in several cortical and subcortical areas, its role in higher functions has been largely ignored. We examined the significance of CART in memory formation and tested if the downstream actions of CART involve N-methyl-d-aspartate (NMDA) activated extra-cellular signal-regulated kinase (ERK). Newly formed memory was evaluated using novel object recognition test consisting of familiarization (T1) and choice trials (T2). The choice trials were performed at two time points: 30 min (T230-min ) and 24-h (T224-h ) postacquisition. In choice trial (T230-min ), vehicle control rats explored the novel object for significantly longer duration than the familiar object indicating intact memory formation. However, CART antibody, U0126 [ERK antagonist, both via intracerebroventricular (icv) or intrahippocampal (ih) route] or MK-801 (NMDA antagonist; intraperitoneal) treated rats spent less time exploring novel objects; CART peptide (icv or ih) was ineffective. During choice trial at T224-h , a significant decrease in novel object exploration time was noticed in vehicle control rats suggesting amnesia. However, treatment with CART, prior to familiarization trial (T1), promoted exploration of the novel object even at T224-h . Pretreatment with U0126 or MK 801 blocked pro-cognitive-like effect of CART suggesting involvement of NMDA-ERK pathway in CART's action. Animals subjected to the object familiarization trial showed a drastic increase in the CART-immunoreactivity in the cells of cornu ammonis 3 and polymorph layer of dentate gyrus, and fibers within ento- (ENT) and peri-rhinal (PRH) cortices. Western blot analysis revealed that CART treatment significantly up-regulated the expression of phospo-ERK1/2 in hippocampus, ENT and PRH. This effect was attenuated following pretreatment with U0126 or MK-801, suggesting the activation of ERK signaling cascade through NMDA receptors. Thus, CART system seems to play an important role in recognition memory and that these effects may be mediated by NMDA receptors-ERK signaling in the ENT/PRH hippocampal circuit. (c) 2016 Wiley Periodicals, Inc. PMID- 27258935 TI - The Role of Unlicensed Assistive Personnel in the Provision of Infusion Therapy. PMID- 27258936 TI - Origin of Multiple Formula Use to Calculate Intraocular Lens Power-Reply. PMID- 27258937 TI - Impaired Vasodilatory Responses of Omental Arteries to CGRP Family Peptides in Pregnancies Complicated by Fetal Growth Restriction. AB - RATIONALE: Calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), and adrenomedullin2 (ADM2)/intermedin are potent vasorelaxant peptides considered to play a role in the adaptive mechanisms in rat pregnancy through increased vasodilation in mesenteric and uterine artery. OBJECTIVE: This study was designed to demonstrate the response of omental arteries (OA) to vasoactive peptides CGRP, ADM, and ADM2 in pregnancy complications such as fetal growth restriction (FGR), and assess the changes in the expression of their receptor components in segments of OA from FGR pregnancy compared to the control. FINDINGS: The findings for this study are: 1) relaxation responses of OA were higher for bradykinin (78.55 +/- 3.91 vs 52.67 +/- 2.19; P < .05) in pregnancy with FGR compared to the normal, 2) relaxation response of OA segments to CGRP was similar with no change in the expression of G-protein couple receptor-calcitonin receptor-like receptor complex in normal healthy pregnancy and pregnancy complicated by FGR, 3) maximal relaxation response of OA were significantly (P < .05) lower for both ADM (18.2 +/- 6.7 vs 38 +/- 2.5) and ADM2 (26.9 +/- 6.7 vs 48 +/- 2.6) along with decreases in their respective ligand-receptor complex in FGR compared to the normal pregnancies, 4) expression of calcitonin receptor-like receptor mRNA was higher but its immunoreactivity was lower in OA from FGR pregnancy compared to the normal, and 5) mRNA and protein levels of RAMP1, RAMP2, and RAMP3 were lower in OA isolated from FGR pregnancies compared to the normal. CONCLUSION: The current study demonstrates that FGR is associated with an increase in the sensitivity of OA to bradykinin and decreased sensitivity for ADM and ADM2 ligand-receptor system with no change in the response for CGRP compared to the normal healthy pregnancy, and suggests a potential role for ADM and ADM2 in the pathophysiology of maternal vasculature in FGR pregnancy. PMID- 27258938 TI - Insulin Plays a Permissive Role for the Vasoactive Effect of GIP Regulating Adipose Tissue Metabolism in Humans. AB - CONTEXT AND OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) in combination with hyperinsulinemia increases blood flow and triglyceride (TAG) clearance in subcutaneous (sc) abdominal adipose tissue in lean humans. The present experiments were performed to further investigate the role of insulin for the vasoactive effect of GIP in adipose tissue metabolism and whether the vasodilatory effect of GIP is dependent on C-peptide. METHODS: Six lean healthy subjects were studied. The sc abdominal adipose tissue metabolism was assessed by Fick's principle during GIP infusion (1.5 pmol/kg/min) in combination with 1) euglycemic-high insulinemic clamp (Eugluc-Hiinsu), raising plasma insulin concentrations to postprandial levels, 2) hyperglycemic-euinsulinemic clamp (Hygluc-Euinsu), and 3) hyperglycemic-hyperinsulinemic clamp, raising plasma insulin concentrations to supraphysiological levels. During the hyperglycemic clamps, endogenous insulin and C-peptide secretion were inhibited by infusion of the somatostatin analogue octreotide. RESULTS: During GIP infusion, Eugluc Hiinsu, and hyperglycemic-hyperinsulinemic clamps, sc abdominal adipose tissue blood flow (ATBF) was similar and increased from 2.1 +/- 0.2 and 2.2 +/- 0.4 ml min(-1) (100 g tissue)(-1) to 7.1 +/- 0.6 and 7.6 +/- 0.1 ml min(-1) (100 g tissue)(-1), respectively (P < .01). ATBF remained virtually constant (2.7 +/- 0.4 ml min(-1) [100 g tissue](-1)) during Hygluc-Euinsu and GIP infusion. In addition, adipose tissue TAG clearance increased significantly (P = .03), whereas free fatty acid output (P = .01), glycerol output (P = .02) and free fatty acid/glycerol release ratio (P = .04) decreased during the Eugluc-Hiinsu clamp compared to Hygluc-Euinsu clamp with GIP. CONCLUSION: In healthy lean humans, insulin is permissive for GIP to induce an increase in blood flow and TAG clearance in sc abdominal adipose tissue. This effect is independent of C peptide. PMID- 27258939 TI - Microfluidic Cell Deformability Assay for Rapid and Efficient Kinase Screening with the CRISPR-Cas9 System. AB - Herein we report a CRISPR-Cas9-mediated loss-of-function kinase screen for cancer cell deformability and invasive potential in a high-throughput microfluidic chip. In this microfluidic cell separation platform, flexible cells with high deformability and metastatic propensity flowed out, while stiff cells remained trapped. Through deep sequencing, we found that loss of certain kinases resulted in cells becoming more deformable and invasive. High-ranking candidates identified included well-reported tumor suppressor kinases, such as chk2, IKK alpha, p38 MAPKs, and DAPK2. A high-ranking candidate STK4 was chosen for functional validation and identified to play an important role in the regulation of cell deformability and tumor suppression. Collectively, we have demonstrated that CRISPR-based on-chip mechanical screening is a potentially powerful strategy to facilitate systematic genetic analyses. PMID- 27258940 TI - N-Substituted Dicyanomethylphenyl Radicals: Dynamic Covalent Properties and Formation of Stimuli-Responsive Cyclophanes by Self-Assembly. AB - Dynamic covalent bonds and their chemistry have been of particular interest both from a fundamental and materials science aspect. Demonstrated herein is that triphenylamine (TPA) and carbazole (Cz), substituted with a dicyanomethyl radical, are useful motifs for dynamic covalent chemistry as they have the appropriate bond strength between monomer units as well as high stability and synthetic simplicity. TPA and Cz units substituted by two dicyanomethyl radicals formed macrocyclic oligomers classified as novel types of azacyclophanes, and in particular, the TPA-based diradical gave a cyclic dimer in almost quantitative yield. The cyclic oligomers exhibited thermo- and mechanochromic behavior resulting from the generation of radical species by intermonomer C-C bond cleavage. PMID- 27258941 TI - Nanoscale imaging and hydrophobicity mapping of the antimicrobial effect of copper on bacterial surfaces. AB - Copper has a long historical role in the arena of materials with antimicrobial properties. Various forms of copper ranging from surfaces to impregnation in textiles and particles, have attracted considerable interest owing to their versatility, potency, chemical stability, and low cost. However, the effects and mechanisms of their antimicrobial action is still unclear. In this study, the effect of copper particles on Escherichia coli was studied at the nanoscale using atomic force microscopy (AFM). Time-lapse AFM images at the single cell level show the morphological changes on live E. coli during antimicrobial treatment, in which for the first time, this process was followed in situ on the same cell over time. AFM-based hydrophobicity mapping further showed that incubating cells with Cu decreased the surface hydrophobicity with an increase of incubation time. Specifically, we are able to visualize both morphology and physico-chemical nature of the bacterial cell surface change in response to copper treatment, leading to the membrane damage and cytoplasm leakage. Overall, the time-lapse AFM imaging combined with hydrophobicity mapping approach presented here provides spatio-temporal insight into the antimicrobial mechanisms of copper at the single cell level, and can be applied to design of better metallic antimicrobial materials as well as investigate different microorganisms. PMID- 27258943 TI - Chromatographic resolution of angiotensin II receptor antagonists (sartans). AB - First time a simple, sensitive and unified quantification method has been developed to analyze the complete class of angiotensin II receptor antagonists which are used in the treatment of hypertension either alone or in combination with some other drugs. The most important advantage of developed method was that the eight separate drugs can be determined on a single chromatographic system without modifications in detection wavelength and mobile phase. The drugs were separated on a Purospher Star 4.6mm*25cm, 5MUm, C18 column maintained at 40 degrees C with 1mLmin(-1) flow rate using ultra violet detection at 254nm. Good separation (Rs>2.0) was achieved in a short analysis allowing simultaneous determination of all eight sartans. The effect of variation in flow rate, detection wavelength and column oven temperature was also studied. The proposed method was statistically validated in terms of precision, accuracy, linearity, specificity and robustness. The newly developed method proved to be specific, robust and accurate for the quantification of eight sartans in commercial pharmaceutical formulations. PMID- 27258942 TI - Health-Related Quality of Life in Athletes: A Systematic Review With Meta Analysis. AB - CONTEXT: Assessment of health-related quality of life (HRQOL) after injury is important. Differences in HRQOL between nonathletes and athletes and between injured and uninjured athletes have been demonstrated; however, the evidence has not been synthesized. OBJECTIVE: To answer the following questions: (1) Does HRQOL differ among adolescent and collegiate athletes and nonathletes? (2) Does HRQOL differ between injured adolescent and collegiate athletes or between athletes with a history of injury and uninjured athletes or those without a history of injury? DATA SOURCES: We systematically searched CINAHL, MEDLINE, SPORTDiscus, and PubMed. A hand search of references was also conducted. STUDY SELECTION: Studies were included if they used generic instruments to compare HRQOL outcomes between athletes and nonathletes and between uninjured and injured athletes. Studies were excluded if they did not use a generic instrument, pertained to instrument development, or included retired athletes or athletes with a chronic disease. DATA EXTRACTION: We assessed study quality using the modified Downs and Black Index Tool. Bias-corrected Hedges g effect sizes and 95% confidence intervals (CIs) were calculated. The Strength of Recommendation Taxonomy (SORT) was used to determine the overall strength of the recommendation. A random-effects meta-analysis was performed for all studies using the composite or total score. DATA SYNTHESIS: Eight studies with modified Downs and Black scores ranging from 70.6% to 88.4% were included. For question 1, the overall random-effects meta-analysis was weak (effect size = 0.27, 95% confidence interval = 0.14, 0.40; P < .001). For question 2, the overall random-effects meta analysis was moderate (effect size = 0.68, 95% confidence interval = 0.42, 0.95; P < .001). CONCLUSIONS: Grade A evidence indicates that athletes reported better HRQOL than nonathletes and that uninjured athletes reported better HRQOL than injured athletes. However, the overall effect for question 1 was weak, suggesting that the differences between athletes and nonathletes may not be clinically meaningful. Clinicians should monitor HRQOL after injury to ensure that all dimensions of health are appropriately treated. PMID- 27258944 TI - Incidence and Clinical Impact of Stroke Complicating Transcatheter Aortic Valve Implantation: Results From the German TAVI Registry. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as a safe and effective treatment for patients with severe, symptomatic aortic valve stenosis at high surgical risk over the last years. However, besides its minimal invasive character, TAVI still is an invasive procedure usually performed in a population, carrying a substantial risk for vascular complications, like stroke. Stroke is known to be a rare but serious complication of transvascular interventions in clinical practice, which is associated with high morbidity and mortality rates. Despite broad clinical research in many fields of TAVI over the last years, only sparse data still exist on the incidence and clinical risk factors of stroke complicating TAVI in clinical practice today. METHODS: We analyzed data of 1.413 TAVIs, which were enrolled at 30 sites into the prospective and multicenter German TAVI Registry from January 2009 until June 2010. RESULTS: The overall incidence of cerebrovascular events complicating TAVI was 3.2% (n = 45/1.413) in a real-world population today. 40% of all cerebrovascular events were classified as transient ischemic attacks (TIA) with symptoms lasting < 24 hr (18/45) and 60% were classified as stroke with symptoms persisting > 24 hr (27/45). All strokes complicating TAVI of 50% were classified as major strokes leading to notable disability in patients, who survive this complication (Modified Ranking Scale 3-6). In-hospital mortality rate in patients with stroke/TIA was 28.9%, compared to 6.9% in patients without stroke/TIA and 1 year mortality rate 46.7% versus 18.6%, respectively. In multivariate analysis, prior stroke and renal impairment were found as the only independent predictors for stroke complicating TAVI. CONCLUSIONS: Stroke complicating TAVI is a serious complication with a clinically relevant incidence even in daily practice leading to a fivefold increase in 30-day-mortality rate, as well as a significant increase in morbidity and disability in patients, who survive this devastating complication. Further research is needed to identify risk factors and ways to reduce stroke after TAVI. (c) 2016 Wiley Periodicals, Inc. PMID- 27258946 TI - Utilizing the eigenvectors of freeway loop data spatiotemporal schematic for real time crash prediction. AB - The concept of crash precursor identification is gaining more practicality due to the recent advancements in Advanced Transportation Management and Information Systems. Investigating the shortcomings of the existing models, this paper proposes a new method to model the real time crash likelihood based on loop data through schematic eigenvectors. Firstly, traffic volume, occupancy and density spatiotemporal schematics in certain duration before an accident occurrence were constructed to describe the traffic flow status. Secondly, eigenvectors and eigenvalues of the spatiotemporal schematics were extracted to represent traffic volume, occupancy and density situation before the crash occurrence. Thirdly, by setting the vectors in crash time as case and those at crash free time as control, a logistic model is constructed to identify the crash precursors. Results show that both the eigenvectors and eigenvalues can significantly impact the accident likelihood compared to the previous study, the proposed model has the advantage of avoiding multicollinearity, better reflection of the overall traffic flow status before the crash, and improving missing data problem of loop detectors. PMID- 27258947 TI - Antimicrobial Resistance and Virulence Factors of Escherichia coli in Cheese Made from Unpasteurized Milk in Three Cities in Brazil. AB - The production of cheeses from unpasteurized milk is still widespread in Brazil, even with a legal ban imposed on its marketing. The manufacture of this cheese is a public health problem, due to the use of raw milk and the poor hygienic conditions throughout the supply chain process. Contamination may occur from several sources and involve several different pathogenic microorganisms, such as Escherichia coli. The latter can cause different clinical manifestations depending on the pathotype involved. Furthermore, some isolates manifest antimicrobial resistance and may be a risk for public health. The purpose of the current study was to investigate the presence of potentially pathogenic E. coli in raw-milk cheese in Brazil and their possible risk to public health. A total of 83 cheeses were collected from three different cities and 169 E. coli isolates were characterized for the presence of enteropathogenic E. coli, Shigatoxigenic E. coli, enterotoxigenic E. coli, extraintestinal pathogenic E. coli (ExPEC) virulence genes, phylogenetic type, antimicrobial resistance, O serogroup, and pulsed-field gel electrophoresis. The number of samples positive for E. coli was highest in Aracaju (90.32%, 28/31). The prevalence of samples positive for potential ExPEC genes was similar for Uberaba and Aracaju (23.07%); the most prevalent ExPEC virulence genes were tsh, iucD, and papC. Isolates from Uberaba had a higher prevalence of resistance to tetracycline (38.46%), amoxicillin/clavulanic acid (58.85%), and ampicillin (61.54%) than the other cities. Overall, antimicrobial resistance genes tetB, blaTEM, and blaCMY-2 were the most prevalent genes (26.32%, 15.79%, and 28.95%, respectively) and the most prevalent serotypes were O4 (8%), 018 (12%), and O23 (8%). Clones originating from the same regions and from different regions were observed. These results emphasize the presence of a potential danger for humans in the consumption of raw milk cheeses in three cities in Brazil due to the presence of antimicrobial resistance, which should be monitored. PMID- 27258945 TI - Cortical thickness and metabolite concentration in chronic stroke and the relationship with motor function. AB - BACKGROUND: Hemiparesis is one of the most prevalent chronic disabilities after stroke. Biochemical and structural magnetic resonance imaging approaches may be employed to study the neural substrates underpinning upper-extremity (UE) recovery after chronic stroke. OBJECTIVE: The purposes of this study were to 1) quantify anatomical and metabolic differences in the precentral gyrus, and 2) test the relationships between anatomical and metabolic differences, and hemiparetic arm function in individuals in the chronic stage of stroke recovery. Our hypotheses were: 1) the Stroke group would exhibit reduced precentral gyrus cortical thickness and lower concentrations of total N-acetylaspartate (tNAA) and glutamate+glutamine (Glx) in the ipsilesional motor cortex; and 2) that each of these measures would be associated with UE motor function after stroke. METHODS: Seventeen individuals with chronic (>6 months) subcortical ischemic stroke and eleven neurologically healthy controls were recruited. Single voxel proton magnetic resonance spectroscopy (H1MRS) was performed to measure metabolite concentrations of tNAA and Glx in the precentral gyrus in both ipsilesional and contralesional hemispheres. Surface-based cortical morphometry was used to quantify precentral gyral thickness. Upper-extremity motor function was assessed using the Wolf Motor Function Test (WMFT). RESULTS: Results demonstrated significantly lower ipsilesional tNAA and Glx concentrations and precentral gyrus thickness in the Stroke group. Ipsilesional tNAA and Glx concentration and precentral gyrus thickness was significantly lower in the ipsilesional hemisphere in the Stroke group. Parametric correlation analyses revealed a significant positive relationship between precentral gyrus thickness and tNAA concentration bilaterally. Multivariate regression analyses revealed that ipsilesional concentrations of tNAA and Glx predicted the largest amount of variance in WMFT scores. Cortical thickness measures alone did not predict a significant amount of variance in WMFT scores. CONCLUSION: While stroke impairs both structure and biochemistry in the ipsilesional hemisphere our data suggest that tNAA has the strongest relationship with motor function. PMID- 27258948 TI - A stable genetic polymorphism underpinning microbial syntrophy. AB - Syntrophies are metabolic cooperations, whereby two organisms co-metabolize a substrate in an interdependent manner. Many of the observed natural syntrophic interactions are mandatory in the absence of strong electron acceptors, such that one species in the syntrophy has to assume the role of electron sink for the other. While this presents an ecological setting for syntrophy to be beneficial, the potential genetic drivers of syntrophy remain unknown to date. Here, we show that the syntrophic sulfate-reducing species Desulfovibrio vulgaris displays a stable genetic polymorphism, where only a specific genotype is able to engage in syntrophy with the hydrogenotrophic methanogen Methanococcus maripaludis. This 'syntrophic' genotype is characterized by two genetic alterations, one of which is an in-frame deletion in the gene encoding for the ion-translocating subunit cooK of the membrane-bound COO hydrogenase. We show that this genotype presents a specific physiology, in which reshaping of energy conservation in the lactate oxidation pathway enables it to produce sufficient intermediate hydrogen for sustained M. maripaludis growth and thus, syntrophy. To our knowledge, these findings provide for the first time a genetic basis for syntrophy in nature and bring us closer to the rational engineering of syntrophy in synthetic microbial communities. PMID- 27258949 TI - Torn apart and reunited: impact of a heterotroph on the transcriptome of Prochlorococcus. AB - Microbial interactions, whether direct or indirect, profoundly affect the physiology of individual cells and ultimately have the potential to shape the biogeochemistry of the Earth. For example, the growth of Prochlorococcus, the numerically dominant cyanobacterium in the oceans, can be improved by the activity of co-occurring heterotrophs. This effect has been largely attributed to the role of heterotrophs in detoxifying reactive oxygen species that Prochlorococcus, which lacks catalase, cannot. Here, we explore this phenomenon further by examining how the entire transcriptome of Prochlorococcus NATL2A changes in the presence of a naturally co-occurring heterotroph, Alteromonas macleodii MIT1002, with which it was co-cultured for years, separated and then reunited. Significant changes in the Prochlorococcus transcriptome were evident within 6 h of initiating co-culture, with groups of transcripts changing in different temporal waves. Many transcriptional changes persisted throughout the 48 h experiment, suggesting that the presence of the heterotroph affected a stable shift in Prochlorococcus physiology. These initial transcriptome changes largely corresponded to reduced stress conditions for Prochlorococcus, as inferred from the depletion of transcripts encoding DNA repair enzymes and many members of the 'high light inducible' family of stress-response proteins. Later, notable changes were seen in transcripts encoding components of the photosynthetic apparatus (particularly, an increase in PSI subunits and chlorophyll synthesis enzymes), ribosomal proteins and biosynthetic enzymes, suggesting that the introduction of the heterotroph may have induced increased production of reduced carbon compounds for export. Changes in secretion-related proteins and transporters also highlight the potential for metabolic exchange between the two strains. PMID- 27258950 TI - Prophages mediate defense against phage infection through diverse mechanisms. AB - The activity of bacteriophages poses a major threat to bacterial survival. Upon infection, a temperate phage can either kill the host cell or be maintained as a prophage. In this state, the bacteria carrying the prophage is at risk of superinfection, where another phage injects its genetic material and competes for host cell resources. To avoid this, many phages have evolved mechanisms that alter the bacteria and make it resistant to phage superinfection. The mechanisms underlying these phentoypic conversions and the fitness consequences for the host are poorly understood, and systematic studies of superinfection exclusion mechanisms are lacking. In this study, we examined a wide range of Pseudomonas aeruginosa phages and found that they mediate superinfection exclusion through a variety of mechanisms, some of which affected the type IV pilus and O-antigen, and others that functioned inside the cell. The strongest resistance mechanism was a surface modification that we showed is cost-free for the bacterial host in a natural soil environment and in a Caenorhabditis. elegans infection model. This study represents the first systematic approach to address how a population of prophages influences phage resistance and bacterial behavior in P. aeruginosa. PMID- 27258951 TI - Evidence for persistent and shared bacterial strains against a background of largely unique gut colonization in hospitalized premature infants. AB - The potentially critical stage of initial gut colonization in premature infants occurs in the hospital environment, where infants are exposed to a variety of hospital-associated bacteria. Because few studies of microbial communities are strain-resolved, we know little about the extent to which specific strains persist in the hospital environment and disperse among infants. To study this, we compared 304 near-complete genomes reconstructed from fecal samples of 21 infants hospitalized in the same intensive care unit in two cohorts, over 3 years apart. The genomes represent 159 distinct bacterial strains, only 14 of which occurred in multiple infants. Enterococcus faecalis and Staphylococcus epidermidis, common infant gut colonists, exhibit diversity comparable to that of reference strains, inline with introduction of strains from infant-specific sources rather than a hospital strain pool. Unlike other infants, a pair of sibling infants shared multiple strains, even after extensive antibiotic administration, suggesting overlapping strain-sources and/or genetic selection drive microbiota similarities. Interestingly, however, five strains were detected in infants hospitalized three years apart. Three of these were also detected in multiple infants in the same year. This finding of a few widely dispersed and persistent bacterial colonizers despite overall low potential for strain dispersal among infants has implications for understanding and directing healthy colonization. PMID- 27258952 TI - An Epic Summer. PMID- 27258953 TI - Daily Informal Multidisciplinary Intensive Care Unit Operational Debriefing Provides Effective Support for Intensive Care Unit Nurses. AB - BACKGROUND: Although most organizations have comprehensive formal stress management programs, an approach that is most likely to be helpful is the one that is curtailed specifically to the needs of a particular nursing unit. With that aim in mind, a process of daily intensive care unit (ICU) multidisciplinary operational debriefings was developed. These operational debriefings use the same concepts as traditional debriefing, yet are offered on a daily basis, rather than being reserved only for major stressful events. Furthermore, they are informal, brief (15 minutes), and multidisciplinary (intensivists, ICU nurses, chaplain, ICU social worker, ICU nutritionist, and ICU pharmacist). The purpose of this descriptive study was to determine the perceptions of attendees in relation to the implementation of daily operational debriefings. METHODS: Six months into the process, the attendees were requested to fill out an anonymous voluntary survey. Questions were simple, straightforward, and close ended. RESULTS: Of 47 potential respondents (42 nurses, 2 nurse managers, 1 social worker, 1 pharmacist, and 1 nutritionist), 42 completed the survey. Results revealed that an overwhelming majority felt that daily operational debriefings provide an effective unit-based support system, a sense of connectedness, and a commitment to the well-being of others. Nearly 50% of the respondents felt that the overall stress level in the ICU decreased, and 98% indicated operational daily debriefings should continue. CONCLUSION: Daily Informal multidisciplinary ICU operational debriefing provides an effective support system for ICU nurses. A modified model could be replicated for non-ICU units as well. PMID- 27258954 TI - Angioedema: Clinical Presentations and Pharmacological Management. AB - Angioedema (AE) is a unique clinical presentation of an unchecked release of bradykinin. The origin of this clinical presentation can be either genetic or acquired. The outcome within the patient is subcutaneous swelling of the lower layers of the epidermis. Symptoms are most often localized to the upper airway or the gastrointestinal tract. A typical course resolves in 5 to 7 days, but in some patients, the clinical manifestations exist up to 6 weeks. Hereditary AE is rare and genetically linked, and typically, the patient has episodes for many years before diagnosis. Episodes of acquired AE may be drug induced, triggered by a specific allergen, or idiopathic. Angioedema can elicit the need for critical care interventions, for advanced airway management, or unnecessary abdominal surgery. The treatment for these patients is evolving as new pharmacological agents are developed. This article addresses subtypes of AE, triggers, pharmacology, and information for interdisciplinary team planning of individualized case management. PMID- 27258955 TI - Myasthenia Gravis Presentation After a Cervical Laminectomy With Fusion. AB - Myasthenia gravis is a chronic neuromuscular disorder that causes skeletal muscle weakness. Typically, myasthenia gravis affects the ocular, bulbar, neck, proximal limbs, and respiratory muscles. Although the presentation is typically observed with complaints of vision and bulbar symptoms such as diplopia, dystonia, and dysphagia, this article presents a case study of an elderly man with a history of increasing upper extremity weakness with complaints of worsening hand dexterity and intermittent episodes of expressive aphasia. After cervical laminectomy with fusion, this gentleman was admitted to the medical intensive care unit, in a complete myasthenic crisis. PMID- 27258956 TI - Women's Sexual Issues After Myocardial Infarction: A Literature Review. AB - BACKGROUND: Sexual activity after myocardial infarction (MI) is a concern for patients and often a challenge for health care professionals to address. It is widely recognized that most patients, of both sexes, report sexual problems or concerns after MI. However, there are reported differences between men and women. Women with sexual concerns may seek less help from health care providers and are more inclined to conceal them because of cultural barriers. OBJECTIVE: The aim of the current study is to present a comprehensive review of the literature describing women's sexual issues after MI. METHOD: A systematic search of the relevant literature was performed within international databases, including PubMed/Medline, Scopus, ScienceDirect, and ProQuest, as well as Google Scholar using relevant keywords. Also, Persian electronic databases such as Magiran, Scientific Information Databases, and Iran Medex were searched from the inception to October 2014. Articles focusing on the sexual issues after MI only in women, as well as articles on both sexes where women's results could be separated, were included in this review. RESULTS: A total of 8 articles were included in the final dataset. The main themes of women's sexual concerns after MI were "loss or decrease of sexual activity," "dissatisfaction of sexual relationship," "doubt about resumption time of sexual activity," "fear of reinfarction or sudden death during sexual activity after MI," "knowledge deficit regarding sexual activity after MI," and "poor performance of health care providers in sexual counseling." DISCUSSION: The results of this review demonstrate that women's post-MI sexual activity is affected by many concerns. The concerns may be a knowledge deficit related to not receiving necessary consultation on this topic. Nurses, as first line care givers, can provide appropriate consultation and education for patients post-MI. As a result, breaking taboo imposed by cultural barriers, personal assumptions, or lack of confidence on giving sexual consultation may ultimately help patients to improve their quality of life. PMID- 27258958 TI - Effectiveness of Decolonization With Chlorhexidine and Mupirocin in Reducing Surgical Site Infections: A Systematic Review. AB - BACKGROUND: Surgical site infections (SSI) are a serious complication of surgery. Staphylococcus aureus (S aureus) is 1 of the most common causative organisms responsible for SSI. Patients who are carriers of methicillin-resistant S aureus and methicillin-sensitive S aureus are at increased risk of developing S aureus associated SSIs. Decolonization of skin with chlorhexidine and nares with mupirocin may reduce the risk of SSI. OBJECTIVE: The primary object of this systematic review is to examine the effectiveness of preoperative universal decolonization of skin with chlorhexidine and nares with intranasal mupirocin in preventing SSIs. METHODS: The following databases were searched: Ovid Medline (from 1946 to September week 3, 2015), Embase (1947 to 2015, week 38), EBSCO CINHAL (1980-2015), Cochrane Collaboration for Systematic Reviews, EBM Reviews, and Google Scholar. STUDY SELECTION: All experimental and nonexperimental studies that evaluated the effect of chlorhexidine in combination with intranasal mupirocin for decolonization were included. Inclusion was limited to published studies written in English. A total of 19 studies were included in this review. One study was deleted from final analysis as other agents were used for skin decolonization. DATA EXTRACTION: Data were extracted independently by 2 members of the study team. Discrepancies were resolved through discussion. RESULTS: Decolonization with topical chlorhexidine and intranasal mupirocin resulted in reduction of S aureus SSI and methicillin-resistant S aureus nosocomial infection and eradication of S aureus nasal carriage. Incidence of SSIs was significantly reduced in 10 studies, which was the primary outcome. Four of the 10 studies used preoperative universal decolonization and significant reduction in SSI was observed in cardiac and orthopedic patients. CONCLUSION: The results of this review indicate the combination of topical chlorhexidine and intranasal mupirocin is effective in reducing S aureus-associated SSIs. PMID- 27258959 TI - The Belmont Report: The Triple Crown of Research Ethics. AB - The Belmont Report is a critical document for those involved in research. However, the report is also applicable to clinical practice. The primary purpose of the Belmont Report is to protect the rights of all research subjects or participants. The Belmont Report also serves as an ethical framework for research. There are 3 major components: (1) respect for persons, (2) beneficence, and (3) justice. This article will review these principles and show how they can be applied to the clinical as well as the research setting and address some concerns for the 21st century. PMID- 27258961 TI - Targeted Temperature Management: Effects of Initial Protocol Implementation on Patient Outcomes. AB - BACKGROUND: Targeted temperature management (TTM) is a strategy used by critical care nurses to mitigate negative effects of out-of-hospital cardiac arrest (OHCA); however, integration and compliance of TTM protocols into routine clinical practice can be challenging. OBJECTIVES: The aims of this study are to (1) investigate the effects of initial TTM protocol implementation on patient mortality, length of stay, and discharge disposition among patients who experience OHCA and (2) evaluate initial compliance and potential barriers to newly implemented TTM protocol. METHODS: A retrospective cohort design was used. Data were gathered on adult patients experiencing OHCA before and after immediate implementation of a TTM protocol within a large academic public hospital. Demographic and clinical data were abstracted from medical records of both TTM and non-TTM groups. Additional compliance data were gathered on the TTM group. Outcome variables included hospital mortality, length of stay, and discharge disposition. RESULTS: Total accrual was 259. Mortality decreased after protocol implementation (89.4%, 75%, P < .05), which was supported in the regression analyses (P = .05; odds ratio, 2.8). A higher proportion of subjects were discharged home after the TTM protocol (21.5% discharged home after protocol implementation vs 5.1% discharged home before protocol implementation; P < .05). Full protocol compliance was 30%. Protocol documentation was inconsistent across units and personnel. CONCLUSIONS: Findings suggest that even initial implementation of TTM protocols can result in positive patient outcomes. Full compliance with protocols remains difficult. Critical care nurses are integral to initiation of and adherence to therapeutic hypothermia protocols and are in a key position to develop strategies for improved compliance across departments. PMID- 27258962 TI - Moral Distress: A Qualitative Study of Emergency Nurses. AB - BACKGROUND: Although many nursing studies have focused on moral distress, very few have looked at moral distress and emergency nurses despite the fact that this group works in stressful, fast-paced environments that often involve situations that can lead to moral distress. OBJECTIVES: The goals of this qualitative study are to determine how emergency nurses define moral distress, describe the experiences of moral distress by emergency nurses and its impact, and identify possible strategies to combat moral distress. METHOD: This study used a phenomenological qualitative design. A convenience sample was used and included 8 registered nurses from 3 different emergency departments in a midsized urban county in the South Central United States. A structured open-ended interview technique was used. RESULTS: Four major themes were identified: (1) there was no face of the family, (2) asking God for forgiveness, (3) flipping the switch, and (4) it changes who we are. DISCUSSION: Nurses in this study all reported experiencing moral distress. Sources of moral distress identified included patient advocacy issues, professional behavior of other health care professionals, internal conflicts with what they perceived to be the right thing to do and that which was asked of them, and guilt over their own feelings about patient care. These nurses described effective and ineffective coping mechanisms. PMID- 27258963 TI - Pediatric Research Abstracts. PMID- 27258964 TI - The Library: A Changing Community. PMID- 27258965 TI - Sodium-Oxygen Batteries: A Comparative Review from Chemical and Electrochemical Fundamentals to Future Perspective. AB - Alkali metal-oxygen (Li-O2 , Na-O2 ) batteries have attracted a great deal of attention recently due to their high theoretical energy densities, comparable to gasoline, making them attractive candidates for application in electrical vehicles. However, the limited cycling life and low energy efficiency (high charging overpotential) of these cells hinder their commercialization. The Li-O2 battery system has been extensively studied in this regard during the past decade. Compared to the numerous reports of Li-O2 batteries, the research on Na O2 batteries is still in its infancy. Although, Na-O2 batteries show a number of attractive properties such as low charging overpotential and high round-trip energy efficiency, their cycling life is currently limited to a few tens of cycles. Therefore, understanding the chemistry behind Na-O2 cells is critical towards enhancing their performance and advancing their development. Chemical and electrochemical reactions of Na-O2 batteries are reviewed and compared with those of Li-O2 batteries in the present review, as well as recent works on the chemical composition and morphology of the discharge products in these batteries. Furthermore, the determining kinetics factors for controlling the chemical composition of the discharge products in Na-O2 cells are discussed and the potential research directions toward improving Na-O2 cells are proposed. PMID- 27258966 TI - Surface charge-induced EDL interaction on the contact angle of surface nanobubbles. AB - The contact angle (CA) of surface nanobubbles is believed to affect the stability of nanobubbles and fluid drag in micro/nanofluidic systems. The CA of nanobubbles is dependent on size and is believed to be affected by the surface charge-induced electrical double layer (EDL). However, neither of these of attributes are well understood. In this paper, by introducing an EDL-induced electrostatic wetting tension, a theoretical model is first established to study the effect of EDLs formed near the solid-liquid interface and the liquid-nanobubble interface on the gas phase CA of nanobubbles. The size-dependence of this EDL interaction is studied as well. Next, by using atomic force microscopy (AFM), the effect of the EDL on nanobubbles' gas phase CA is studied with variable electrical potential at the solid-liquid interface, which is adjusted by an applied voltage. Both the theoretical and the experimental results show that the EDLs formed near the solid liquid interface and the liquid-nanobubble interface lead to a reduction of gas phase CA of the surface nanobubbles because of an electrostatic wetting tension on the nanobubble due to the attractive electrostatic interaction between the liquid and nanobubble within the EDL, which is in the nanobubbles' outward direction. An EDL with a larger zeta potential magnitude leads to a larger gas phase CA reduction. Furthermore, the effect of EDL on the nanobubbles' gas phase CA shows a significant size-dependence considering the size dependence of the electrostatic wetting tension. The gas phase CA reduction due to the EDL decreases with increasing nanobubble height and increases with the nanobubble's increasing curvature radius, indicating that a surface charge-induced EDL could possibly explain the size dependence of the gas phase CA of nanobubbles. PMID- 27258967 TI - Organocatalytic Asymmetric Mannich Reaction of 3-Hydroxyoxindoles/3 Aminooxindoles with in Situ Generated N-Boc-Protected Aldimines for the Synthesis of Vicinal Oxindole-Diamines/Amino Alcohols. AB - A highly efficient asymmetric Mannich reaction of 3-monosubstituted 3 aminooxindoles/3-hydroxyoxindoles with in situ generated N-Boc-protected aldimines catalyzed by the chiral bifunctional thiourea-tertiary amine catalyst has been developed. Under mild reaction conditions, a series of structurally diverse vicinal oxindole-diamines/amino alcohols were smoothly obtained in moderate to high yields (up to 99%) with good to excellent diastereoselectivities and enantioselectivities (up to 95:5 dr and 96% ee). The synthetic application of this protocol was also demonstrated by the versatile transformation of chiral vicinal oxindole-diamine/amino alcohol into spirocyclic oxindoles. PMID- 27258968 TI - Innovative radiotherapy of sarcoma: Proton beam radiation. AB - This review on proton beam radiotherapy (PBT) focusses on an historical overview, cost-effectiveness, techniques, acute and late toxicities and clinical results of PBT for sarcoma patients. PBT has gained its place among the armamentarium of modern radiotherapy techniques. For selected patients, it can be cost-effective. PMID- 27258970 TI - The Transcriptional Regulation of FOXO Genes in Thyrocytes. AB - FOXO transcription factors are key regulators of DNA damage repair, proliferation and apoptosis in thyrocytes. Thyroid malignancies show impaired FOXO function. In this study, we investigated the transcriptional regulation of FOXO isoforms in thyroid epithelial cells. mRNA expression of FOXO isoforms (FOXO1, 3 and 4) was determined in FRTL-5 cells stimulated with different growth factors and H2O2. Furthermore, the impact of PI3K/AKT signalling on FOXO transcription was investigated in PI3K p110alpha mutant FRTL-5 cells and regulatory dependence of FOXO transcription on FOXO was studied in FRTL-5 cells with hFOXO3 overexpression. Finally, mRNA expression levels of FOXO isoforms were determined in human epithelial thyroid tumours. Growth factor deprivation induced transcription of FOXO1, 3 and 4, whereas insulin stimulation decreased FOXO1 and FOXO4 transcription in FRTL-5 cells. Inhibition of the PI3K/AKT cascade amplified FOXO1 and FOXO4 expression. In contrast, H2O2 and TSH did not influence FOXO transcription in thyrocytes. Overexpression of PI3K p110alpha inhibited FOXO3 and induced FOXO4 transcription. In human thyroid tumours, FOXO1 and FOXO3 mRNA levels were significantly downregulated in papillary thyroid carcinoma when compared to normal tissues. In contrast, follicular thyroid carcinomas showed significant upregulation of FOXO4 mRNA.In this paper, we demonstrate an influence of PI3K signalling on FOXO transcription in thyrocytes. Moreover, we show that thyroid cancers exhibit alterations in FOXO transcription besides the previously reported alterations in posttranslational FOXO3 regulation. These findings may add to the concept of targeting the PI3K pathway in advanced thyroid cancers. PMID- 27258969 TI - Implementation of mechanism of action biology-driven early drug development for children with cancer. AB - An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric malignancies, are evaluated in early phase clinical trials, and that this approach to generate pre-clinical and clinical data is systematically pursued by academia, sponsors, industry, and regulatory bodies to bring new paediatric oncology drugs to front-line therapy more rapidly. PMID- 27258971 TI - A Single Dose of the Anti-Resorptive Peptide Human Calcitonin Paradoxically Augments Particle- and Endotoxin-Mediated Pro-Inflammatory Cytokine Production In Vitro. AB - The peptide hormone calcitonin (CT) is known to inhibit bone resorption and has previously been shown also to prevent particle-induced osteolysis, the leading cause of revision arthroplasty. In the present study, the influence of human CT on the initial inflammatory response to particulate wear debris or bacterial endotoxins, ultimately leading to osteoclast-mediated bone resorption, was analysed in human THP-1 macrophage-like cells. The cells were activated with either ultra-high molecular weight polyethylene (UHMWPE) particles or bacterial lipopolysaccharides (LPS) in order to simulate an osteolysis-associated inflammatory response. The cells were simultaneously treated with human CT (10( 9) M). Cytokine production of tumour necrosis factor (TNF)-alpha was quantified on both RNA and protein levels while interleukins (IL)-1beta and IL-6 were measured as secreted protein only. Stimulation of the cells with either particles or LPS led to a dose- and time-dependent increase of TNF-alpha mRNA production and protein secretion of TNF-alpha, IL-1beta, and IL-6. Application of CT mostly enhanced cytokine production as elicited by UHMWPE particles while a pronounced transient inhibitory effect on LPS-induced inflammation became evident at 24 h of incubation. Human CT displayed ambivalent effects on the wear- and LPS-induced production of pro-inflammatory cytokines. Thereby, the peptide primarily upregulated particle-induced inflammation while LPS-induced cytokine secretion was temporarily attenuated in a distinct manner. It needs to be evaluated whether the pro- or anti-inflammatory action of CT contributes to its known anti resorptive effects. Thus, the therapeutic potential of the peptide in the treatment of either particle- or endotoxin-mediated bone resorption could be determined. PMID- 27258972 TI - Organophotocatalytic Generation of N- and O-Centred Radicals Enables Aerobic Oxyamination and Dioxygenation of Alkenes. AB - A cooperative TEMPO and photoredox catalytic strategy was applied for the first time to the direct conversion of N-H and O-H bonds into N- and O-centred radicals, enabling a general and selective oxidative radical oxyamination and dioxygenation of various beta,gamma-unsaturated hydrazones and oximes. In the reaction, O2 was employed not only as a terminal oxidant but also as the oxygen source. This protocol provided efficient access to the synthesis of various synthetically and biologically important pyrazoline, pyridazine and isoxazoline derivatives under metal-free and mild reaction conditions. Mechanistic studies revealed that the cooperative organophotocatalytic system functions through two single-electron-transfer (SET) processes. PMID- 27258989 TI - eta(6) -Arene-Zirconium-PNP-Pincer Complexes: Mechanism of Their Hydrogenolytic Formation and Their Reactivity as Zirconium(II) Synthons. AB - The cyclometalated monobenzyl complexes [(Cbzdiphos(R) -CH)ZrBnX] 1 (iPr) Cl and 1 (Ph) I reacted with dihydrogen (10 bar) to yield the eta(6) -toluene complexes [(Cbzdiphos(R) )Zr(eta(6) -tol)X] 2 (iPr) Cl and 2 (Ph) I (cbzdiphos=1,8 bis(phosphino)-3,6-di-tert-butyl-9H-carbazole). The arene complexes were also found to be directly accessible from the triiodide [(Cbzdiphos(Ph) )ZrI3 ] through an in situ reaction with a dibenzylmagnesium reagent and subsequent hydrogenolysis, as exemplified for the eta(6) -mesitylene complex [(Cbzdiphos(Ph) )Zr(eta(6) -mes)I] (3 (Ph) I). The tolyl-ring in 2 (iPr) Cl adopts a puckered arrangement (fold angle 23.3 degrees ) indicating significant arene-1,4-diido character. Deuterium labeling experiments were consistent with an intramolecular reaction sequence after the initial hydrogenolysis of a Zr-C bond by a sigma-bond metathesis. A DFT study of the reaction sequence indicates that hydrogenolysis by sigma-bond metathesis first occurs at the cyclometalated ancillary ligand giving a hydrido-benzyl intermediate, which subsequently reductively eliminates toluene that then coordinates to the Zr atom as the reduced arene ligand. Complex 2 (Ph) I was reacted with 2,6-diisopropylphenyl isocyanide giving the deep blue, diamagnetic Zr(II) -diisocyanide complex [(Cbzdiphos(Ph) )Zr(CNDipp)2 I] (4 (Ph) I). DFT modeling of 4 (Ph) I demonstrated that the HOMO of the complex is primarily located as a "lone pair on zirconium", with some degree of back-bonding into the C=N pi* bond, and the complex is thus most appropriately described as a zirconium(II) species. Reaction of 2 (Ph) I with trimethylsilylazide (N3 TMS) and 2 (iPr) Cl with 1-azidoadamantane (N3 Ad) resulted in the formation of the imido complexes [(Cbzdiphos(R) )Zr=NR'(X)] 5 (iPr) Cl-NAd and 5 (Ph) I-NTMS, respectively. Reaction of 2 (iPr) Cl with azobenzene led to N-N bond scission giving 6 (iPr) Cl, in which one of the NPh-fragments is coupled with the carbazole nitrogen to form a central eta(2) -bonded hydrazide(-1), whereas the other NPh-fragment binds to zirconium acting as an imido-ligand. Finally, addition of pyridine to 2 (iPr) Cl yielded the dark purple complex [(Cbzdiphos(iPr) )Zr(bpy)Cl] (7 (iPr) Cl) through a combination of CH-activation and C-C-coupling. The structural data and UV/Vis spectroscopic properties of 7 (iPr) Cl indicate that the bpy (bipyridine) may be regarded as a (dianionic) diamido-type ligand. PMID- 27258991 TI - Examining a hypothetical quantitative model for better approximation of culprit coronary artery and site of stenosis on 99mTc-sestamibi gated myocardial perfusion SPECT. AB - A hypothetical quantitative model of analyzing gated myocardial perfusion SPECT is proposed and examined for the feasibility of its use as a predictor of diseased coronary artery and approximating the site of stenosis to determine whether it could serve as a useful noninvasive complement for coronary angiography. The extent and severity of perfusion defects on rest gated myocardial perfusion imaging SPECT-images were assessed on a five-point scale in a standard 17-segment model and total perfusion deficit was quantified by automated software. The first step was to locate the diseased coronary artery using a quantitative method: for this, the score of each segment belonging to a particular coronary artery was determined using a systematic presumptive approach. After determination of specific coronary artery segments, the scores of the contiguous segments in three short axis slices (apical, middle, and basal) were summed for six subdivisions (anterior, anterolateral, inferolateral, inferior, anteroseptal, and inferoseptal). The site of stenosis was determined from (a) the initial approximation of the involved segments with a defect score of 2-4 and (b) subsequent calculation of the defect score of each of the six subdivisions and allocating the site through a preassigned number for each coronary artery. For each coronary artery, only the subdivision with the highest defect score was considered. Proximal, middle, and distal segments of left anterior descending artery (LAD) were considered to be represented when the summed value of a subdivision within a particular arterial territory was more than or equal to 7, between 5 and 7, 5 and 3, respectively. For the left circumflex and right coronary artery, summed scores (of respective subdivisions) of more than or equal to 5 and between 3 and 5 were preassigned to proximal and distal stenosis, respectively. The results were then correlated with the coronary angiographic data. On coronary angiography, proximal LAD occlusion was considered when the site of occlusion occurred proximal to the first diagonal branch and a mid-LAD occlusion from the first diagonal branch to the next diagonal branch. Proximal left circumflex artery occlusion is considered as those located before the first relevant marginal branch and distal left circumflex artery occlusion is beyond the first marginal branch. From the ostium to the origin of the first acute marginal artery was considered the proximal segment of the right coronary artery and thereafter was designated as distal. The result obtained by the quantitative model was compared with the angiographic data along with statistical analysis. The unweighted kappa-value was 0.803 and 95% confidence interval was between 0.716 and 0.890. Both the proposed quantitative myocardial perfusion imaging model and the angiographic results were in strong agreement; however, this model needs to be examined in a larger number of patients in a prospective setting to explore its pitfalls and define its practical applicability in future. PMID- 27258990 TI - Evaluation of motion-correction methods for dual-gated cardiac positron emission tomography/computed tomography imaging. AB - BACKGROUND: Dual gating is a method of dividing the data of a cardiac PET scan into smaller bins according to the respiratory motion and the ECG of the patient. It reduces the undesirable motion artefacts in images, but produces several images for interpretation and decreases the quality of single images. By using motion-correction techniques, the motion artefacts in the dual-gated images can be corrected and the images can be combined into a single motion-free image with good statistics. AIM: The aim of the present study is to develop and evaluate motion-correction methods for cardiac PET studies. We have developed and compared two different methods: computed tomography (CT)/PET-based and CT-only methods. METHODS: The methods were implemented and tested with a cardiac phantom and three patient datasets. In both methods, anatomical information of CT images is used to create models for the cardiac motion. RESULTS: In the patient study, the CT-only method reduced motion (measured as the centre of mass of the myocardium) on average 43%, increased the contrast-to-noise ratio on average 6.0% and reduced the target size on average 10%. Slightly better figures (51, 6.9 and 28%) were obtained with the CT/PET-based method. Even better results were obtained in the phantom study for both the CT-only method (57, 68 and 43%) and the CT/PET-based method (61, 74 and 52%). CONCLUSION: We conclude that using anatomical information of CT for motion correction of cardiac PET images, both respiratory and pulsatile motions can be corrected with good accuracy. PMID- 27258992 TI - The Association Between Corticomotor Excitability and Motor Skill Learning in People With Painful Hand Arthritis. AB - OBJECTIVES: Previous studies have shown a tendency for reduced motor cortex inhibition in chronic pain populations. People with chronic pain also routinely demonstrate motor deficiencies, including skill learning. The goals of the current study were to (1) provide a thorough analysis of corticomotor and intracortical excitability in people with chronic arthritic hand pain, and (2) examine the relationship between these measures and performance on a motor skill learning task. METHODS: Twenty-three people with arthritic hand pain and 20 pain free controls participated in a cross-sectional study. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of the first dorsal interosseus muscle. Participants then completed a 30-minute motor skill training task involving the index finger of the same hand. RESULTS: Hand arthritis participants showed evidence of reduced intracortical inhibition and enhanced facilitation, which correlated with duration of hand pain. Arthritis participants were initially poorer at the motor skill task but over the total training time performance was equivalent between groups. There were no associations found between measures of intracortical excitability and motor skill learning. DISCUSSION: Our findings are the first to provide evidence of cortical disinhibition in people with painful arthritis, as previously demonstrated in other chronic pain populations. Cortical excitability changes may progress the longer pain persists, with increased pain duration being associated with greater cortical disinhibition. There was no evidence that these changes in cortical excitability are related to impaired motor function or skill learning. PMID- 27258994 TI - Active Trigger Points in the Cervical Musculature Determine the Altered Activation of Superficial Neck and Extensor Muscles in Women With Migraine. AB - OBJECTIVE: Previous studies have demonstrated the presence of active trigger points (TrPs) in women with migraine reproducing their headache attacks. No study has investigated whether these TrPs can alter cervical muscle function in migraine. Our objective was to analyze differences in the activation of superficial neck flexor and extensor muscles in women with migraine considering the presence of active TrPs in the splenius capitis (SC), the upper trapezius (UT), and the sternocleidomastoid (SCM) muscles. METHODS: Surface electromyography (EMG) was recorded from the superficial flexors (SCM and anterior scalene) and the extensor (SC, UT) muscles bilaterally as participants performed a staged task of cranio-cervical flexion (CCF; 5 contractions representing a progressive increase in CCF range of motion) in 70 women with migraine. They were stratified according to the presence or the absence of active TrPs in the SCM, the SC, or the UT musculature. A comparison of EMG normalized root mean square (RMS) values was conducted with a 2*5 analysis of covariance with the task level as the within-subject variable, group stratified by active TrPs as the between-subjects variable and the presence of neck pain as a covariable. RESULTS: All patients exhibited active TrPs in their cervical muscles, which reproduced their migraine. Women with migraine exhibiting active TrPs in the SCM (P<0.01), the UT (P<0.05), or the SC (P<0.05) muscles had lower normalized RMS values of their superficial neck flexors than those without active TrPs in the same muscles. In addition, individuals exhibiting active TrPs in the SC and the UT (both, P<0.05) muscles had higher normalized RMS values in the SC muscle than those without active TrPs in the same muscles. CONCLUSIONS: The presence of active TrPs in the cervical musculature determines an altered activation of superficial neck and extensor muscles during low-load, isometric CCF contractions in women with migraine. PMID- 27258993 TI - All Fatigue is Not Created Equal: The Association of Fatigue and Its Subtypes on Pain Interference in Orofacial Pain. AB - OBJECTIVES: Fatigue is known to be a pathway through which depression, psychological distress, pain intensity, and sleep disturbance influence pain interference, but the independent effects of fatigue on pain interference after controlling for these variables remains unknown. In addition, no study to date has tested whether fatigue subtypes of general fatigue, mental fatigue, emotional fatigue, physical fatigue, or vigor differentially predict pain interference. METHODS: The current study tested these associations using archival medical data of 2133 chronic orofacial pain patients, who completed a battery of psychological questionnaires at the time of their first appointment at an orofacial pain clinic. RESULTS: Hierarchical linear regression analysis revealed that after controlling for depression, psychological distress, sleep disturbance, pain intensity, and demographic variables, fatigue predicted higher pain interference (B=0.70, SE=0.17, P<0.001, eta=0.01). Physical fatigue (B=1.70, SE=0.48, P<0.001, eta=0.01) and vigor (B=-3.24, SE=0.47, P<0.001, eta=0.03) were independently associated with pain interference after controlling for the aforementioned variables. DISCUSSION: The findings suggest that fatigue is an important independent predictor of pain interference and not merely a mediator. These findings also suggest that not all fatigue is created equal. Interventions aimed at reducing pain interference should target specific fatigue symptoms of physical fatigue and vigor. Future research investigating the independent associations of fatigue subtypes on pain outcomes may help clarify the nature of the interrelationships between pain and fatigue. PMID- 27258995 TI - Prevalence of Chronic Neck Pain, Low Back Pain, and Knee Pain and Their Related Factors in Community-Dwelling Adults in Iran: A Population-based National Study. AB - BACKGROUND: Chronic musculoskeletal pain (CMP) is increasing in prevalence rapidly. Over the past 2 decades low back pain has been ranked globally as the primary cause of years lived with disability. The primary objective of this study was to investigate the prevalence of chronic neck pain (CNP), chronic low back pain (CLBP), and chronic knee pain (CKP) and their related risk factors in the national Iranian population. METHODS: We analyzed data obtained through a cross sectional, population-based survey of 7889 Iranians who were aged between 30 and 70 years. RESULTS: The prevalence of CNP, CLBP, and CKP was 15.34%, 27.18%, and 29.97%, respectively. Female sex, aging, body mass index>=25, Lur or Arab ethnicity, illiteracy, passive smoking, positive osteoporosis history, and low or high physical activity levels were risk factors for CLBP, CNP, and CKP after adjustment for potential confounders. For example, in participants with a body mass index>=30, odds ratios for CNP, CLBP, and CKP adjusted for age, sex, ethnicity, living area, education, employment status, smoking, and physical activity levels were 1.26 (95% confidence interval [CI], 1.04-1.52), 1.37 (95% CI, 1.17-1.59), and 1.64 (95% CI, 1.41-1.91), respectively. CONCLUSIONS: This is the first study investigating the prevalence of CNP, CLBP, and CKP in the national population of Iran. It shows some modifiable risk factors for CMP, and suggests that affordable planning for these risk factors can be valuable in preventing CMP globally. However, this is a cross-sectional study and future longitudinal studies in this field are necessary. PMID- 27258996 TI - Pain Experiences of Children and Adolescents With Osteogenesis Imperfecta: An Integrative Review. AB - OBJECTIVE: Pain is a commonly experienced symptom for children and adolescents diagnosed with osteogenesis imperfecta (OI). The purpose of this integrative review was to describe the pain experience of children and adolescents with OI as well as critically appraise the content and methods of studies assessing OI pain. METHODS: Five electronic bibliographic databases were searched. Published quantitative, qualitative, and/or mixed-method studies assessing pain in children and adolescents with OI were included and appraised. Constant comparison of the extracted data was used to synthesize themes. RESULTS: A total of 783 titles were identified, and 19 studies that met the inclusion criteria were included in this review. Study appraisal scores ranged from 25.0% to 83.3% using the Quality Assessment Tool. The majority of studies included assessed pain as a secondary outcome (63%) and less than half used moderately established or well-established tools (42%). Two themes were uncovered: "Pain is Present and Problematic" and "Issues with Pain Assessment." Key findings under each theme include: (1) the negative impacts of pain and the substandard use of pain management strategies; and (2) the lack of multidimensional and consistent pain assessments, as well as difficulties in assessing pain in younger children. DISCUSSION: Research on OI has focused very little on pain experience in children and adolescents, and there is no standard method of assessing pain. To better describe the pain experience of these patients, future research should focus on better characterizing OI pain with the use of age-appropriate valid, reliable, and multidimensional pain assessment tools. PMID- 27258997 TI - Prediction of Postoperative Pain From Electrical Pain Thresholds After Laparoscopic Cholecystectomy. AB - OBJECTIVE: Early postoperative pain correlates to persisting pain, psychosocial distress, and delayed mobilization with thromboembolic and infectious complications. Electrical pain thresholds (EPT) have shown promising results in being able to predict postoperative pain, but the results are conflicting. The aim of this study was to test whether EPT levels can be used to predict the postoperative pain in patients of both sexes. MATERIALS AND METHODS: One hundred eighty patients scheduled for laparoscopic cholecystectomy were included in this prospective clinical study. Individual levels of EPT were measured before surgery, and the pain intensity was evaluated in the early postoperative period. RESULTS: There were significant correlations between EPT and the maximum postoperative pain intensity (rs=-0.21, P=0.009), time to the first rescue opioid (rs=0.26, P=0.006), and the total dose of rescue opioid (rs=-0.22, P=0.001). The interaction test showed significant influence of the sex on the ability of EPT to predict the postoperative pain intensity. Female patients with low EPT (<15) had a 4.5 times higher risk of postoperative pain (P=0.003). DISCUSSION: Levels of EPT are reproducible, and the technique is well tolerated. However, it can be used to predict postoperative pain only in women. A weak correlation with the postoperative pain intensity, found here as well as previously, and the high sex dependency of the EPT levels obtained considerably limit the predictive value of this technique for routine use in perioperative clinical practice. PMID- 27258998 TI - Epidural Against Systemic Analgesia: An International Registry Analysis on Postoperative Pain and Related Perceptions After Abdominal Surgery. AB - BACKGROUND: The PAIN OUT registry collected data from >30,000 patients on pain on the first postoperative day in hospitals worldwide. Utilizing the database, we compared systemic and epidural analgesia (EA) on postoperative pain and related side-effects in patients after abdominal surgeries (ASs). METHODS: ASs were identified through the ICD9-Code and subgrouped into laparoscopic surgery and open surgery. After identifying patients in this subset with and without EA, propensity-score matching was performed on the basis of demographics and comorbidities. Primary outcomes were different qualities of pain, and secondary outcomes were pain-related sensations and treatment-related side effects measured with the numeric rating scale. They were calculated as the risk ratio (RR) using the median as the divisor. RESULTS: The database contained 29,108 cases, with 5365 AS, and 646 cases remained after matching. A risk analysis revealed that for the AS group, EA posed a significantly lower risk for the perception of worst pain (RR, 0.75; confidence interval [CI], 0.64-0.87), least pain (RR, 0.61; CI, 0.5-0.75), time in severe pain (RR, 0.61; CI, 0.5-0.75), in-bed activity interference of pain (RR, 0.71; CI, 0.59-0.85), pain interference with coughing (RR, 0.68; CI, 0.57-0.82) or sleeping (RR, 0.73; CI, 0.61-0.87), and a higher chance of pain relief (RR, 1.5; CI, 1.23-1.83). The risk for itchiness (RR, 2.23; CI, 1.62-3.07) appeared to be higher, as did the probability of satisfaction (RR, 1.25; CI, 1.03-1.51). The risk for feeling helpless (RR, 0.83; CI, 0.7-0.99) and drowsiness (RR, 0.74; CI, 0.63-0.88) was reduced. Both subgroups showed similar tendencies. DISCUSSION: Regarding the pain intensity, satisfaction, and relatable side-effects, EA seems to be superior compared with systemic analgesia after AS. PMID- 27258999 TI - Clinical and immunological studies of 49 cases of various types of intercellular IgA dermatosis and 13 cases of classical subcorneal pustular dermatosis examined at Kurume University. AB - BACKGROUND: Intercellular IgA dermatosis (IAD) is a subset of autoimmune bullous disease exclusively with IgA antikeratinocyte cell-surface antibodies. The classification and pathogenesis of this condition are still obscure. OBJECTIVES: To classify IAD and study its pathogenesis. METHODS: From our cohort of 5402 cases of autoimmune bullous disease, we selected 49 cases of various types of intercellular IgA dermatosis (IAD) and 13 cases of classical subcorneal pustular dermatosis (SPD), for which sera and information were available. We studied these cases clinically and immunologically. RESULTS: There were 17 SPD-type IAD, 12 intraepidermal neutrophilic IgA dermatosis (IEN)-type IAD, two IgA-pemphigus vegetans, four IgA-pemphigus foliaceus, six IgA-pemphigus vulgaris and eight unclassified IAD cases. There was no sex predominance, and the average age at disease onset was 45.9 years. Clinically, bullous and pustular skin lesions developed on various sites, particularly intertriginous areas. Histopathology showed intraepidermal blisters or pustules at the upper epidermis in the SPD-type and at the midepidermis in the IEN-type. Immunological studies revealed that direct immunofluorescence, indirect immunofluorescence of normal human skin and enzyme-linked immunosorbent assays (ELISAs) of recombinant proteins of desmogleins and desmocollins frequently showed positive results, although no antigens were detected in many cases. All cases of classical SPD, which showed no positive immunological results, were indistinguishable clinically and histopathologically from SPD-type IAD. CONCLUSIONS: The present study of the largest cohort of cases of IAD showed that the major subtypes are SPD and IEN, and that the combination of indirect immunofluorescence and ELISAs of desmogleins and desmocollins, in addition to direct immunofluorescence, was useful for the diagnosis of IAD and its subtypes. PMID- 27259000 TI - Cell wall composition plays a key role on sensitivity of filamentous fungi to chitosan. AB - Chitosan antifungal activity has been reported for both filamentous fungi and yeast. Previous studies have shown fungal plasma membrane as main chitosan target. However, the role of the fungal cell wall (CW) in their response to chitosan is unknown. We show that cell wall regeneration in Neurospora crassa (chitosan sensitive) protoplasts protects them from chitosan damage. Caspofungin, a beta-1,3-glucan synthase inhibitor, showed a synergistic antifungal effect with chitosan for N. crassa but not for Pochonia chlamydosporia, a biocontrol fungus resistant to chitosan. Chitosan significantly repressed N. crassa genes involved in beta-1,3-glucan synthesis (fks) and elongation (gel-1) but the chitin synthase gene (chs-1) did not present changes in its expression. N. crassa cell wall deletion strains related to beta-1,3-glucan elongation (Deltagel-1 and Deltagel 2) were more sensitive to chitosan than wild type (wt). On the contrary, chitin synthase deletion strain (Deltachs-1) showed the same sensitivity to chitosan than wt. The mycelium of P. chlamydosporia showed a higher (ca. twofold) beta-1,3 glucan/chitin ratio than that of N. crassa. Taken together, our results indicate that cell wall composition plays an important role on -sensitivity of filamentous fungi to chitosan. PMID- 27259002 TI - Physical therapy interventions for gross motor skills in people with an intellectual disability aged 6 years and over: a systematic review. AB - AIM: The systematic review was undertaken to investigate the effectiveness of physical therapy interventions for improving gross motor skills (GMSs) in people with an intellectual disability aged 6 years and older. There is a lack of physical therapy research for GMSs in this population, and no prior systematic review. People with an intellectual disability may require specific teaching approaches within therapy interventions to accommodate their cognitive and learning needs. People with an intellectual disability who suffer from GMS deficits can benefit from physical therapy to help improve their GMSs. METHODS: Data sources were PubMed, CINAHL, Embase, and ProQuest. Reference lists of relevant identified articles were also hand searched. Papers published in English from 1 January 2008 to 22 October 2014 were considered for inclusion. This start date was chosen to reflect the tenets of the United Nations Convention on the Rights of Persons with Disabilities which was ratified in 2008.Eligible study designs for inclusion were randomized controlled trial (RCT), pseudo-RCT, repeated measures, and case report. Overall, 887 potential articles were identified, of which 42 were retrieved for full-text review, and seven were finally included. Critical appraisal was independently conducted by two reviewers using the Joanna Briggs Institute appraisal checklists; no articles were excluded following critical appraisal. Data extraction was performed using Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument data extraction instruments. RESULTS: High heterogeneity between the studies precluded meta-analysis of the results; a narrative synthesis was completed instead. Two RCTs, two pseudo-RCTs, two repeated measures studies, and one case report were included. Studies varied in regard to participants' intellectual disability, and the clinical interventions used. Interventions were well tolerated with negligible adverse effects. Significant improvements were reported for cadence and nondimensionalized gait velocity following body-weight-supported gait training; cadence following lower limb strengthening exercises; and the Gross Motor Function Measure-88 measures following adapted judo training. These results suggest that task-specific training may be useful. However, the overall quality of evidence was low. CONCLUSION: The evidence identified by this systematic review supporting physical therapy for improving GMSs in people with an intellectual disability was limited because of the low quality of studies (only two were RCTs) and only three statistically significant findings. Given the current paucity of evidence, a future systematic review, which sought to identify evidence regarding interventions used by a range of health and education professionals for improving GMSs in people with an intellectual disability, could provide a broader evidence base for clinical interventions which may be utilized by physical therapists. PMID- 27259001 TI - Telomere Length, Long-Term Black Carbon Exposure, and Cognitive Function in a Cohort of Older Men: The VA Normative Aging Study. AB - BACKGROUND: Long-term air pollution exposure has been associated with age-related cognitive impairment, possibly because of enhanced inflammation. Leukocytes with longer telomere length (TL) are more responsive to inflammatory stimuli, yet TL has not been evaluated in relation to air pollution and cognition. OBJECTIVES: We assessed whether TL modifies the association of 1-year exposure to black carbon (BC), a marker of traffic-related air pollution, with cognitive function in older men, and we examined whether this modification is independent of age and of C reactive protein (CRP), a marker of inflammation. METHODS: Between 1999 and 2007, we conducted 1-3 cognitive examinations of 428 older men in the Veterans Affairs (VA) Normative Aging Study. We used covariate-adjusted repeated-measure logistic regression to estimate associations of 1-year BC exposure with relative odds of being a low scorer (<= 25) on the Mini-Mental State Examination (MMSE), which is a proxy of poor cognition. Confounders included age, CRP, and lifestyle and sociodemographic factors. RESULTS: Each doubling in BC level was associated with 1.57 (95% CI: 1.20, 2.05) times higher odds of low MMSE scores. The BC-MMSE association was greater only among individuals with longer blood TL (5th quintile) (OR = 3.23; 95% CI: 1.37, 7.59; p = 0.04 for BC-by-TL-interaction). TL and CRP were associated neither with each other nor with MMSE. However, CRP modified the BC-MMSE relationship, with stronger associations only at higher CRP (5th quintile) and reference TL level (1st quintile) (OR = 2.68; 95% CI: 1.06, 6.79; p = 0.04 for BC-by-CRP-interaction). CONCLUSIONS: TL and CRP levels may help predict the impact of BC exposure on cognitive function in older men. Citation: Colicino E, Wilson A, Frisardi MC, Prada D, Power MC, Hoxha M, Dioni L, Spiro A III, Vokonas PS, Weisskopf MG, Schwartz JD, Baccarelli AA. 2017. Telomere length, long-term black carbon exposure, and cognitive function in a cohort of older men: the VA Normative Aging Study. Environ Health Perspect 125:76-81; http://dx.doi.org/10.1289/EHP241. PMID- 27259003 TI - Knowledge translation and implementation science: what is the difference? PMID- 27259004 TI - Semiempirical Modeling of Ag Nanoclusters: New Parameters for Optical Property Studies Enable Determination of Double Excitation Contributions to Plasmonic Excitation. AB - Quantum mechanical studies of Ag nanoclusters have shown that plasmonic behavior can be modeled in terms of excited states where collectivity among single excitations leads to strong absorption. However, new computational approaches are needed to provide understanding of plasmonic excitations beyond the single excitation level. We show that semiempirical INDO/CI approaches with appropriately selected parameters reproduce the TD-DFT optical spectra of various closed-shell Ag clusters. The plasmon-like states with strong optical absorption comprise linear combinations of many singly excited configurations that contribute additively to the transition dipole moment, whereas all other excited states show significant cancellation among the contributions to the transition dipole moment. The computational efficiency of this approach allows us to investigate the role of double excitations at the INDO/SDCI level. The Ag cluster ground states are stabilized by slight mixing with doubly excited configurations, but the plasmonic states generally retain largely singly excited character. The consideration of double excitations in all cases improves the agreement of the INDO/CI absorption spectra with TD-DFT, suggesting that the SDCI calculation effectively captures some of the ground-state correlation implicit in DFT. These results provide the first evidence to support the commonly used assumption that single excitations are in many cases sufficient to describe the optical spectra of plasmonic excitations quantum mechanically. PMID- 27259005 TI - Cleft Palate and Aglossia Result From Perturbations in Wnt and Hedgehog Signaling. AB - OBJECTIVE: The objective of this study was to explore the molecular basis for cleft secondary palate and arrested tongue development caused by the loss of the intraflagellar transport protein, Kif3a. DESIGN: Kif3a mutant embryos and their littermate controls were analyzed for defects in facial development at multiple stages of embryonic development. Histology was employed to understand the effects of Kif3a deletion on palate and tongue development. Various transgenic reporter strains were used to understand how deletion of Kif3a affected Hedgehog and Wnt signaling. Immunostaining for structural elements of the tongue and for components of the Wnt pathway were performed. BrdU activity analyses were carried out to examine how the loss of Kif3a affected cell proliferation and led to palate and tongue malformations. RESULTS: Kif3a deletion causes cranial neural crest cells to become unresponsive to Hedgehog signals and hyper-responsive to Wnt signals. This aberrant molecular signaling causes abnormally high cell proliferation, but paradoxically outgrowths of the tongue and the palatal processes are reduced. The basis for this enigmatic effect can be traced back to a disruption in epithelial/mesenchymal signaling that governs facial development. CONCLUSION: The primary cilium is a cell surface organelle that integrates Hh and Wnt signaling, and disruptions in the function of the primary cilium cause one of the most common-of the rarest-craniofacial birth defects observed in humans. The shared molecular basis for these dysmorphologies is an abnormally high Wnt signal simultaneous with an abnormally low Hedgehog signal. These pathways are integrated in the primary cilium. PMID- 27259006 TI - Copper(I) Forms a Redox-Stable 1:2 Complex with alpha-Synuclein N-Terminal Peptide in a Membrane-Like Environment. AB - alpha-Synuclein (alphaS) is the main protein component of Lewy bodies, characterizing the pathogenesis of Parkinson's disease. alphaS is unstructured in solution but adopts a helical structure in its extended N-terminal segment upon association with membranes. In vitro the protein binds avidly Cu(II), but in vivo the protein is N-acetylated, and Cu(II) binding is lost. We have now clarified the binding characteristics of the Cu(I) complex with the truncated alphaS peptide 1-15, both in N-acetylated and free amine forms, in a membrane mimetic environment and found that complexation occurs with a 1:2 Cu(I)-alphaS stoichiometry, where Cu(I) is bound to Met1 and Met5 residues of two helical peptide chains. The resulting tetrahedral Cu(I) center is redox-stable, does not form reactive oxygen species, and is unreactive against dopamine in the presence of O2. This suggests that, unlike cytosolic Cu(I)-alphaS, which retains the capacity to activate O2 and promote oxidative reactions, membrane-bound Cu(I) alphaS may serve as a sink for unreactive copper. PMID- 27259007 TI - ETV6-NTRK3 Is Expressed in a Subset of ALK-Negative Inflammatory Myofibroblastic Tumors. AB - Inflammatory myofibroblastic tumor (IMT) is a genetically heterogenous tumor of the viscera and soft tissues, with multiple molecular features having been demonstrated in this tumor type. About 50% of cases harbor an anaplastic lymphoma kinase (ALK) gene rearrangement, and recent studies have described novel fusions involving the ROS1 and PDGFRbeta genes in a subset of ALK-negative cases. However, the molecular features of the remaining subset of cases are not yet defined. We report a case of a large, highly aggressive IMT of the lung in a 17 year-old girl. This case was molecularly characterized through whole-genome and transcriptome sequencing. Subsequently, we investigated a cohort of 15 ALK negative IMTs of various anatomic sites. All cases were screened using fluorescence in situ hybridization (FISH) for rearrangement of the ETV6 locus and with reverse transcription polymerase chain reaction (RT-PCR) for the ETV6-NTRK3 fusion transcript. Whole-genome and transcriptome sequencing revealed an ETV6 NTRK3 fusion transcript in our index case. This was confirmed by FISH studies for ETV6 gene rearrangement, as well as by RT-PCR. In addition, 2 additional cases in our cohort demonstrated ETV6 rearrangement by FISH. The presence of ETV6-NTRK3 fusion transcript was demonstrated by RT-PCR in one of these additional cases. In summary, we demonstrate the expression of the ETV6-NTRK3 fusion oncogene in a small subset of IMTs, lending further support to the role of oncogenic tyrosine kinases in the pathophysiology of this tumor type. Our data also further expand the growing spectrum of tumor types expressing the ETV6-NTRK3 fusion. PMID- 27259008 TI - Pathologic Response of HER2-positive Gastric Cancer to Trastuzumab-based Chemotherapy. AB - Trastuzumab-based chemotherapy is now a standard approach for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer. However, histopathologic changes after treatment have yet to be elucidated. This study aims to characterize the histologic response of gastric cancer to trastuzumab treatment and its correlation with HER2 status. Twenty-one advanced HER2-positive gastric cancers treated with trastuzumab-based chemotherapy, including 10 surgically resected specimens and 11 biopsy samples from patients with inoperable tumors, were evaluated for the histologic responses and HER2 status of residual cells. We also reviewed, as controls, 10 cases undergoing surgical resection of tumors after chemotherapy without trastuzumab. Complete and partial histologic responses were obtained in 2 and 8 of the surgical cases, respectively. HER2-positive neoplastic cells were recognized at least focally in the 8 cases. Notably, the proportion of HER2-positive cells was always higher in superficial (mucosal/submucosal) layers than in deeper layers. Three specimens contained HER2-positive neoplastic cells exclusively in the superficial area or intravascular space, whereas deeply invasive or metastatic components almost completely disappeared or were HER2 negative when still present. In contrast, HER2-negative cells or residual tumor cells in control cases tended to survive as well or better in deeply invasive areas or in metastases than in superficial areas. Biopsy samples from nonoperative patients remained HER2 positive after treatment in 8 of 11 patients. Our observations suggest that HER2-positive neoplastic cells tend to survive within superficial areas or intravascular spaces after trastuzumab therapy, even when deeply invasive or metastatic lesions responded well to therapy. PMID- 27259009 TI - Distinctive Patterns of CTNNB1 (beta-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma. AB - Salivary gland basaloid neoplasms are diagnostically challenging. Limited publications report that some basal cell adenomas harbor CTNNB1 mutations, and nuclear beta-catenin expression is prevalent. We evaluated beta-catenin expression in basal cell adenomas and adenocarcinomas in comparison with salivary tumors in the differential diagnosis and performed targeted genetic analysis on a subset of cases. beta-catenin immunohistochemistry was performed on formalin fixed, paraffin-embedded whole sections from 73 tumors. Nuclear staining was scored semiquantitatively by extent and intensity. DNA was extracted from 6 formalin-fixed, paraffin-embedded samples (5 basal cell adenomas, 1 basal cell adenocarcinoma) for next-generation sequencing. Nuclear beta-catenin staining was present in 18/22 (82%) basal cell adenomas; most were diffuse and strong and predominant in the basal component. Two of 3 basal cell adenocarcinomas were positive (1 moderate focal; 1 moderate multifocal). All adenoid cystic carcinomas (0/20) and pleomorphic adenomas (0/20) were negative; 2/8 epithelial myoepithelial carcinomas showed focal nuclear staining. Most beta-catenin negative tumors showed diffuse membranous staining in the absence of nuclear staining. Four of 5 basal cell adenomas had exon 3 CTNNB1 mutations, all c.104T>C (p.I35T). Basal cell adenocarcinoma showed a more complex genomic profile, with activating mutations in PIK3CA, biallelic inactivation of NFKBIA, focal CYLD deletion, and without CTNNB1 mutation despite focal beta-catenin expression. Nuclear beta-catenin expression has moderate sensitivity (82%) for basal cell adenoma but high specificity (96%) in comparison with its morphologic mimics. CTNNB1 mutation was confirmed in most basal cell adenomas tested, and findings in basal cell adenocarcinoma suggest possible tumorigenic mechanisms, including alterations in PI3K and NF-kappaB pathways and transcriptional regulation. PMID- 27259010 TI - CTNNB1 Mutations and Estrogen Receptor Expression in Neuromuscular Choristoma and Its Associated Fibromatosis. AB - Neuromuscular choristoma (NMC) is a very rare, developmental malformation characterized by the endoneurial intercalation of mature muscle fibers among peripheral nerve fibers. NMC typically arises in the major proximal peripheral nerves, most commonly the sciatic nerve, and may involve the lumbosacral and brachial plexus. Patients present clinically with progressive neuropathy or plexopathy. NMC is strongly associated with development of a fibromatosis, histologically identical to conventional desmoid-type fibromatosis (NMC fibromatosis). The development of NMC-fibromatosis is often precipitated by iatrogenic trauma (ie, biopsy). Desmoid-type fibromatosis is characterized by CTNNB1 exon 3 mutations, which result in aberrant nuclear beta-catenin localization and dysregulated canonical Wnt signaling. In contrast, the pathogenesis of NMC and NMC-fibromatosis is unknown. Desmoid-type fibromatosis expresses estrogen receptors (ER), specifically the ER-beta isoform (ERbeta), and endocrine therapies may be used in surgically unresectable cases. In contrast, the ER expression profile of NMC-fibromatosis is unknown. We evaluated a series of NMC and NMC-fibromatosis for CTNNB1 mutations, beta-catenin expression, and ER isoform expression. Five NMCs occurred in 2 female and 3 male patients (median age: 14 y, range <1 to 42 y), as masses involving the sciatic nerve (N=4) or brachial plexus (N=1). Four (of 5) NMCs had CTNNB1 mutations: 3 c.134 C>T (p.S45F) and 1 c.121 A>G (p.T41A). Four patients subsequently developed NMC fibromatosis, and all 4 cases contained CTNNB1 mutations, including 1 p.T41A and 3 p.S45F mutations. In 3 patients, the NMC and NMC-fibromatosis had identical CTNNB1 mutations. Only 1 NMC had no detectable CTNNB1 mutation; however, the patient's subsequent NMC-fibromatosis had a CTNNB1 p.T41A mutation. All NMC and NMC-fibromatosis showed aberrant nuclear localization of beta-catenin, nuclear ERbeta expression, and no ERalpha expression. The presence of CTNNB1 mutations both in NMC and NMC-fibromatosis may be a shared molecular genetic abnormality underlying their pathogenesis. PMID- 27259012 TI - Pure Apocrine Carcinomas Represent a Clinicopathologically Distinct Androgen Receptor-Positive Subset of Triple-Negative Breast Cancers. AB - Apocrine carcinomas comprise ~1% of all breast cancers and are characterized by large cells bearing abundant eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. They are typically estrogen receptor/progesterone receptor/HER2 negative, making them unresponsive to typical hormonal or HER2 based chemotherapy. However, this subtype of triple-negative breast cancers expresses androgen receptor (AR), a feature not shared by most nonapocrine triple negative cancers (NA-TNCs). AR therefore represents a potential diagnostic tool and therapeutic target for apocrine breast carcinoma. All pure apocrine carcinomas diagnosed during a 10-year period were reviewed, and clinicopathologic characteristics were compared with a control group of 26 NA-TNC cases. Twenty apocrine carcinomas were identified (~0.8% of all breast cancers). The mean age at diagnosis was 69.3 years for apocrine carcinomas and 56.7 years for NA-TNC. All apocrine carcinomas and no NA-TNC were AR positive. The proportions of apocrine carcinoma grades varied, with G1 being seen in 15% of patients, G2 in 55%, and G3 in 30%. In contrast, 100% of NA-TNC cases were G3. The majority of apocrine carcinomas presented at low T stage (T1: 70%; T2: 20%; T3: 10%; T4: 0%), whereas NA-TNC cases more often presented at T2 or higher (T1: 46.2%; T2: 30.8%; T3: 11.5%; T4: 11.5%). Thirty percent of apocrine carcinomas and 30.8% of NA-TNCs had nodal metastases at presentation. Apocrine carcinomas had a favorable clinical prognosis, with 80% of patients showing no evidence of disease-related morbidity or mortality (mean follow-up: 45.2 mo). Pure apocrine carcinomas represent a clinicopathologically distinct subgroup of triple-negative breast cancer characterized by AR positivity. When compared with NA-TNC, apocrine carcinomas more often present in older women with lower grade and T stage, a group in which a more conservative treatment regimen is often desired. PMID- 27259011 TI - Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors. AB - The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. To define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3 NTRK1 gene fusions, which were further validated by fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1-negative LPF-NT cases, 1 case each showed ROS1 and ALK gene rearrangements. In contrast, none of the 25 classic LPFs showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21-22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100-positive LPF-NT but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling LPF, but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors. PMID- 27259013 TI - Interstitial Mycosis Fungoides: A Clinicopathologic Study of 21 Patients. AB - Interstitial mycosis fungoides (IMF) is a rare histopathologic variant of mycosis fungoides (MF) that may mimic other inflammatory dermatoses, mainly interstitial granuloma annulare, inflammatory morphea, and interstitial granulomatous dermatitis. Only small series and sporadic case reports of IMF have been described in the literature. We reviewed 27 specimens from 21 patients with IMF (M:F=11:10, median age 60) to better characterize clinical, histopathologic, and immunohistochemical features of this disease. Most patients presented clinically with patches and/or plaques. Conventional MF was documented before, concomitant with, or after IMF in 12 patients, whereas only in 2 patients different biopsies showed exclusive features of IMF over a period of 4 and 191 months, respectively. Histology revealed in all cases variably long, linear aggregates of dermal lymphocytes splaying the collagen fibers, involving predominantly the superficial and mid-dermis (6 cases) or the entire dermis (21 cases). Immunohistochemical stainings revealed a cytotoxic phenotype in 9/18 tested cases. Variable amounts of histiocytes/macrophages were found interstitially in all tested biopsies but never represented a population larger than that of T lymphocytes. Our study shows that IMF is a peculiar variant of MF with frequent cytotoxic phenotype. This histopathologic variant in most cases represents a transient pattern in otherwise conventional MF. Accurate clinicopathologic correlation and phenotypic studies of atypical dermal interstitial lymphohistiocytic infiltrates allow to make a correct diagnosis. PMID- 27259014 TI - Distinct Clinicopathologic and Genetic Features of 2 Histologic Subtypes of Intrahepatic Cholangiocarcinoma. AB - Previous studies have identified 2 clinically significant morphologic subtypes of intrahepatic cholangiocarcinoma (ICC) on the basis of anatomic location and/or histologic appearances. Recognizing that these classification schemes are not always applicable practically, this study aimed to establish a novel classification system based on mucin productivity and immunophenotype and to determine the rationale of this classification by examining the clinicopathologic and genetic characteristics of the 2 subtypes defined by this method. We retrospectively investigated 102 consecutive ICC cases and classified them on the basis of mucin productivity and immunophenotype (S100P, N-cadherin, and NCAM). We found that 42 and 56 cases were classified as type 1 and type 2 ICCs, respectively, and only 4 cases were of indeterminate type. Type 1 ICC, generally characterized by mucin production and diffuse immunoreactivity to S100P, arose less frequently in chronic liver diseases and showed higher levels of serum CEA and CA 19-9 than did type 2 ICC, which generally showed little mucin production and exhibited immunoreactivity to N-cadherin and/or NCAM. Type 1 ICC was characterized by several pathologic features, including higher frequencies of perineural invasion and lymph node metastasis. Although the log-rank test demonstrated that type 1 ICC had significantly worse survival, the multivariate Cox regression analysis showed no prognostic significance of this histologic subtype. Genetic analyses revealed that KRAS mutation was significantly more frequent in type 1 ICC, whereas IDH mutation and FGFR2 translocation were restricted to type 2 ICC. In conclusion, the present classification of ICC based on mucin productivity and immunophenotype identified 2 subtypes with clinicopathologic significance. PMID- 27259015 TI - A Practical Approach to the Classification of WHO Grade 3 (G3) Well differentiated Neuroendocrine Tumor (WD-NET) and Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) of the Pancreas. AB - High-grade neuroendocrine neoplasms (World Health Organization [WHO] G3) of the pancreas include both well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC). According to the WHO classification scheme, the diagnosis of this group of tumors is based on both the histopathology of the tumor and the assessment of proliferation fraction. However, the former can be challenging due to the lack of well-defined histologic criteria, and the latter alone (ie, >20 mitoses/10 high-power fields or Ki67>20%) may not sufficiently distinguish WD-NETs from PD-NECs. Given the considerable differences in treatment strategies and clinical outcome, additional practical modalities are required to facilitate the accurate diagnosis of high-grade pancreatic neuroendocrine neoplasms. We examined 33 cases of WHO G3 neuroendocrine neoplasms of the pancreas and attempted to classify them into WD NET, small cell PD-NEC (PD-NEC-SCC), and large cell PD-NEC (PD-NEC-LCC) or to designate them as "ambiguous" when an uncertain diagnosis was rendered by any of the observers or there was any disagreement in classification among the 3 observers. To simplify the interpretation, both PD-NEC-SCC and PD-NEC-LCC were considered together as PD-NECs in the final analysis. The initial approach was to assess microscopically a single morphologically challenging hematoxylin and eosin section from each case without the knowledge of Ki67 values, performed independently by 3 pathologists to assess the degree of diagnostic concordance, and then evaluate immunohistochemical staining for surrogate biomarkers of known genotypes of WD-NET and PD-NEC, respectively, and, lastly, complete a clinicopathologic review to establish a final definitive classification. Loss of DAXX or ATRX protein expression defined WD-NET, and abnormal p53, Rb, SMAD4 expression signified PD-NEC. When the chosen section displayed an element of WD histopathology, or other tumor sections contained WHO G1/G2 components, or there had been a prior established diagnosis of a primary WD-NET, the final diagnosis was rendered as a WD-NET with high-grade (G3) progression. If a component of conventional adenocarcinoma was present (in slides not seen in the initial review), the diagnosis was established as a combined adenocarcinoma and PD-NEC. All 3 pathologists agreed on the morphologic classification of 33% of the cases (6 WD-NET, 3 PD-NEC-SCC, and 2 PD-NEC-LCC), were conflicted on 2 cases between PD NEC-SCC and PD-NEC-LCC, and disagreed or were uncertain on the classification for the remaining 20 cases (61%), which were therefore categorized as ambiguous. In the group of cases in which all pathologists agreed on the classification, the 6 WD-NET cases had either loss of DAXX or ATRX or had evidence of a WD-NET based on additional or prior pathology slides. The 7 PD-NEC cases had abnormal expression of p53, Rb, and/or SMAD4 or a coexisting adenocarcinoma. In the ambiguous group (n=20), 14 cases were established as WD-NETs, based upon loss of DAXX or ATRX in 7 cases and additional pathology evidence of high-grade progression from WD-NET in the other 7 cases; 5 cases were established as PD-NEC based upon abnormal expression of p53, Rb, and/or SMAD4; 1 case remained undetermined with normal expression of all markers and no evidence of entity-defining histologic findings in other slides. On the basis of the final pathologic classifications, the disease-specific survival was 75 and 11 months for the WD-NET and PD-NEC groups, respectively. Thus, we conclude that morphologic diagnosis of high-grade pancreatic neuroendocrine neoplasms is challenging, especially when limited pathologic materials are available, and necessitates better defined criteria. The analysis of both additional sections and prior material, along with an immunohistochemical evaluation, can facilitate accurate diagnosis in the majority of cases and guide the appropriate clinical management and prognosis. PMID- 27259016 TI - A Novel High-Throughput Viscometer. AB - A novel, rapid, parallel, and high-throughput system for measuring viscosity of materials under different conditions of shear rate, temperature, time, etc., has been developed. This unique system utilizes the transient flow of a complex fluid through pipettes. This approach offers significant practical advantages over microfluidic-based devices for viscosity screening: no cleanup is required, the method is high throughput (<1 h for 100 samples), and only small sample volumes (<1 mL) are used. This paper details for the first time the experimental and modeling efforts to implement this mass- and pressure-based viscosity measurement concept as a robust viscosity estimation tool. This approach is very well-suited for viscosity measurements in high-throughput formulation workflows, as it is rapid and parallel and operates directly on samples in various microtiter plate formats. We present systematic experimental observations together with numerical and analytical modeling approaches to characterize instrument capabilities and limitations. The complex transient flow of fluids through these pipettes leads to data-rich pressure profiles. Numerical and analytical modeling is then used to extract viscosity and other rheological parameters from these pressure profiles. We have successfully utilized this viscosity screening tool for a multitude of complex fluids including oils, paints, solvents, and detergents. PMID- 27259017 TI - Cavitands as Chaperones for Monofunctional and Ring-Forming Reactions in Water. AB - Cyclic processes involving medium-sized rings show low rates because internal strains-torsions and transannular interactions-are created during the reactions. High dilution is often used to slow the competing bi- and higher-molecular processes but cannot accelerate the desired cyclization reaction. Here we apply cavitands to the formation of medium- to large-sized rings through conversion of long-chain diisocyanates to cyclic ureas. The reactions take place in aqueous (D2O) solution, where hydrophobic forces drive the starting materials into the cavitands in folded conformations. The guest assumes the shape to fill the space properly, which brings the reacting ends closer together than they are in bulk solvent. Complexation overcomes some of the internal strains involved in precyclization shapes of the guest molecules and accelerates the cyclization. The results augur well for applications of water-soluble cavitands to related processes such as remote functionalization reactions. PMID- 27259018 TI - Ultrasound Evaluation of the Urinary Bladder in Dogs Following Cystotomy with Full Thickness Suture Placement. AB - The purpose of the study reported here is to determine the long-term effect of full thickness suture placement in the urinary bladder following cystotomy as it relates to urinary bladder mucosal changes identified ultrasonographically at the suture placement site. A retrospective search for dogs that had undergone a cystotomy from 6 to 24 mo prior to the study was performed, yielding 31 dogs included in the study. All dogs had the cystotomy closed using full thickness sutures. These dogs underwent an ultrasound of the urinary bladder to evaluate the mucosa at the incision site. Four (12.9%) of the 31 dogs had mucosal lesions consistent with a polypoid mass or masses. None of these four dogs had lesions solely at the previous cystotomy site. This study confirmed our hypothesis of no long-term evidence of mucosal lesions at the previous cystotomy site closed with full thickness sutures. Based on the results, the use of full thickness suture placement for the closure of the urinary bladder following cystotomy does not result in bladder mucosal changes. Other causes of mucosal changes, such as polypoid mass or masses, should be considered if identified on follow-up ultrasound evaluations following cystotomy procedures regardless of closure technique. PMID- 27259019 TI - Fragmentation of the Medial Coronoid Process in Toy and Small Breed Dogs: 13 Elbows (2000-2012). AB - Fragmentation of the medial coronoid process (FCP) is an uncommon cause of thoracic limb lameness in toy and small breed dogs. Arthroscopic findings and treatment remains poorly described. The objective of this study was to describe the arthroscopic findings and short-term outcome following arthroscopic treatment in toy and small breed dogs with FCP. Medical records were retrospectively reviewed. Arthroscopic findings were available from 13 elbows (12 dogs). Outcome data >=4 wk postoperatively were available for nine elbows. Owner satisfaction scores were available for 10 elbows. Common preoperative findings included lameness, elbow pain, and imaging abnormalities consistent with FCP. Displaced FCP was the most common FCP lesion identified. Cartilage lesions at the medial coronoid process were identified in 92.3% of elbows (n = 12), with a median Outerbridge score of 4 (range 1-5). Concurrent cartilage lesions of the medial humeral condyle were identified in 76.9% of elbows (n = 10). Seven of nine elbows had full or acceptable function postoperatively. Median owner outcome satisfaction was 91% (range 10-100). FCP should be considered a cause of thoracic limb lameness in toy and small breed dogs. Arthroscopy can be safely and effectively used to diagnose and treat FCP in these breeds. PMID- 27259020 TI - 2016 AAHA Oncology Guidelines for Dogs and Cats. AB - All companion animal practices will be presented with oncology cases on a regular basis, making diagnosis and treatment of cancer an essential part of comprehensive primary care. Because each oncology case is medically unique, these guidelines recommend a patient-specific approach consisting of the following components: diagnosis, staging, therapeutic intervention, provisions for patient and personnel safety in handling chemotherapy agents, referral to an oncology specialty practice when appropriate, and a strong emphasis on client support. Determination of tumor type by histologic examination of a biopsy sample should be the basis for all subsequent steps in oncology case management. Diagnostic staging determines the extent of local disease and presence or absence of regional or distant metastasis. The choice of therapeutic modalities is based on tumor type, histologic grade, and stage, and may include surgery, radiation therapy, chemotherapy, immunotherapy, and adjunctive therapies, such as nutritional support and pain management. These guidelines discuss the strict safety precautions that should be observed in handling chemotherapy agents, which are now commonly used in veterinary oncology. Because cancer is often a disease of older pets, the time of life when the pet-owner relationship is usually strongest, a satisfying outcome for all parties involved is highly dependent on good communication between the entire healthcare team and the client, particularly when death or euthanasia of the patient is being considered. These guidelines include comprehensive tables of common canine and feline cancers as a resource for case management and a sample case history. PMID- 27259021 TI - The Modified Maquet Procedure (MMP) in Dogs: Technical Development and Initial Clinical Experience. AB - The literature about tibial tuberosity advancement surgery in dogs and humans informed the development of a version of the operation using a wedge-shaped implant of titanium foam. Computer-assisted drawing and stereolithography was used to create instruments and implants that were evaluated by cadaver surgery. A trial, involving 26 client-owned dogs with lameness due to cranial cruciate ligament failure, was started. Follow-up was done by clinical and radiographic examination after 4 wk and clinical examination again 6-11 mo after surgery. The titanium foam implant maintained tibial tuberosity advancement easily and effectively. The same major complication occurred in 2 of the first 6 cases before, a slightly modified technique was used to treat 20 dogs without complication. At mid-term follow-up (6-11 mo), 20/26 dogs (77%) had returned to full function, two dogs (7.7%) had acceptable function, two dogs (7.7%) could not be evaluated due to recent contra lateral modified Maquet procedure surgery, and two (7.7%) dogs had died for reasons unrelated to the study. This is the first clinical report of the use of titanium foam in veterinary orthopaedics. Modified Maquet procedure appears to be an effective treatment for lameness due to failure of the cranial cruciate ligament in dogs. PMID- 27259022 TI - Inflow Venous Occlusion for Intracardiac Resection of an Occluding Right Ventricular Tumor. AB - Use of normothermic venous inflow occlusion enabled removal of an intracardiac tumor in a 4 yr old, 27 kg, spayed female Airedale terrier with a history of appendicular osteosarcoma and recent exertional syncope. Inflow venous occlusion via a median sternotomy thoracotomy without hypothermia was used to access the mineralized mass within the right ventricular outflow tract. Duration of circulatory arrest was 70 s for this beating heart surgery. A circumscribed intracardiac chondrosarcoma tumor was marginally resected in this dog, successfully alleviating exertional syncope and restoring a normal echogenic appearance of the right heart. Asymptomatic intracardiac chondrosarcoma recurrence and pulmonary metastasis was detected at 309 days and cardiopulmonary arrest occurred 372 days following intracardiac surgery. Use of inflow occlusion is a viable technique for select intracardiac tumors in dogs with preoperative planning. PMID- 27259023 TI - Comparison of Surgically Treated Large Versus Small Intestinal Volvulus (2009 2014). AB - The purpose of this retrospective study was to compare the outcome for dogs with surgically treated large versus small intestinal volvulus between October 2009 and February 2014. A total of 15 dogs met the inclusion criteria and underwent an abdominal exploratory. Nine dogs were diagnosed with large intestinal volvulus during the study period, and all nine had surgical correction for large intestinal volvulus. All dogs were discharged from the hospital. Of the seven dogs available for phone follow-up (74 to 955 days postoperatively), all seven were alive and doing well. Six dogs were diagnosed with small intestinal volvulus during the study period. One of the six survived to hospital discharge. Three of the six were euthanized at the time of surgery due to an extensive amount of necrotic bowel. Of the three who were not, one died postoperatively the same day, one died 3 days later, and one dog survived for greater than 730 days. Results concluded that the outcome in dogs with surgically corrected large intestinal volvulus is excellent, compared with a poor outcome in dogs with small intestinal volvulus. The overall survival to discharge for large intestinal volvulus was 100%, versus 16% for small intestinal volvulus. PMID- 27259024 TI - Occurrence and Clinicopathologic Features of Splenic Neoplasia Based on Body Weight: 325 Dogs (2003-2013). AB - Medical records of 396 dogs undergoing splenectomy for treatment of a splenic mass or nodular disease were reviewed retrospectively. Overall distribution of histopathologic diagnosis and clinicopathologic features were evaluated for 325 dogs that met inclusion criteria. Dogs were dichotomized into two groups based on weight, with the statistically derived cutoff identified as 27.8 kg. Malignancy was diagnosed in 58% of dogs, with no difference between small (55%) and large (61%) dogs (P = .291). Overall, 32% of splenic masses were hemangiosarcoma (HSA), which comprised 25 and 39% of all masses in small and large dogs, respectively. The diagnosis of HSA, non-HSA malignancy, or benign splenic disease was significantly different between the groups (P = .019). Of malignant diagnoses, HSA comprised 46 and 65% of small and large dog splenic neoplasms, respectively (P = .009). In both groups, dogs with HSA were significantly more likely to have preoperative anemia, hemoabdomen, thrombocytopenia, and a blood transfusion, as compared to dogs with non-HSA malignancy or benign lesions. Overall, dogs had similar odds of having a malignant splenic lesion regardless of weight, but dogs <=27.8 kg were significantly less likely to be diagnosed with HSA. PMID- 27259025 TI - Intravenous Lipid Emulsion Therapy for Bromethalin Toxicity in a Dog. AB - Bromethalin is a central nervous system toxin currently incorporated into several different rodenticides. In 2008, the EPA requested that manufacturers phase out second-generation anticoagulant rodenticides. In response, manufacturers began to increase production of bromethalin-based rodenticides. It is likely that pet exposure to bromethalin will increase in the future. Bromethalin has no known antidote and tends to deposit in fat. Intravenous lipid emulsions (ILEs) are being used with increasing frequency in both human and veterinary medicine to treat numerous acute systemic toxicities. A 4 yr old spayed female Pit bull terrier was presented following witnessed ingestion of bromethalin rodenticide by the owners. Decontamination was unsuccessful and ILE was started. Serum was frozen at -80 degrees C before and 1 hr after completion of ILE. In rats, the half-life of desmethylbromethalin, the toxic metabolite, has been reported at 5.6 days and 6 days, and it is likely to be similar in dogs. The only intervention between the pre-lipid serum sample and the post-lipid serum sample was the administration of ILE, and the serum desmethylbromethalin levels were reduced by 75% (from 4 ppb to 1 ppb) during this time. To the authors' knowledge, this is the first report describing treatment of bromethalin ingestion with ILE. PMID- 27259026 TI - Hypercalcemia in a Dog with Chronic Ingestion of Maxacalcitol Ointment. AB - A miniature dachshund male with severe azotemia of unknown cause was referred. Serum biochemistry revealed severe azotemia and hypercalcemia, but serum intact parathormone and parathormone-related protein were normal. Although the owner reported that the dog had never ingested any drugs or supplements, it was revealed that the owner's son used antipsoriatic ointment, maxacalcitol, which contained an active vitamin D3 analogue, daily and the dog often ate the son's dander and licked his skin, especially after he applied the maxacalcitol ointment. After the dog was insulated from the maxacalcitol ointment and the son as much as possible, the hypercalcemia and azotemia improved gradually and had mostly resolved at 3 mo. The dog has been generally free of clinical signs without any treatment for over 2 yr. PMID- 27259027 TI - Thyroglossal Duct Carcinoma in a Cat. AB - A 14 yr old castrated domestic shorthair cat presented for a fluid-filled structure in the ventral cervical region that had been present for 1 yr and had not resolved after repeated aspiration and drainage. Cervical computed tomography showed an approximately 10 cm, fluid-filled, multilobulated mass located on the ventrolateral right side of the cervical region extending into the thoracic inlet. Cytologic examination of the fluid revealed cystic fluid with evidence of chronic hemorrhage. The mass was surgically removed, and histopathologic examination revealed a thyroglossal duct carcinoma. Thyroid and parathyroid gland origin were ruled out by negative immunohistochemical staining for thyroglobulin, parathyroid hormone, calcitonin, and synaptophysin. No adjunctive treatment was performed and no recurrence was noted at 14 mo. Thyroglossal duct carcinoma has not been previously reported in a cat. There are two previous reports of squamous cell carcinoma of the thyroglossal duct in dogs. In humans, with complete removal and no evidence of metastasis, carcinoma of the thyroglossal duct has a good prognosis for recovery. PMID- 27259028 TI - Toad Intoxication in the Dog by Rhinella marina : The Clinical Syndrome and Current Treatment Recommendations. AB - Oral exposure to the secretions of Rhinella marina (formerly Bufo marinus ) can carry a high fatality rate without early and appropriate treatment. In dogs, the clinical syndrome, which is evident almost immediately, manifests in profuse ptyalism along with gastrointestinal, respiratory, and neurologic signs. Severe cardiac arrhythmias develop less frequently. This review will cover the history, toxicology, and clinical syndrome of Rhinella marina intoxication, and will discuss the recommended therapies for stabilization. PMID- 27259029 TI - Prediction of one-year mortality by five different frailty instruments: A comparative study in hospitalized geriatric patients. AB - BACKGROUND: Data comparing the ability of different major frailty instruments for predicting mortality in hospitalized geriatric patients are scare. MATERIAL AND METHODS: 307 patients >=65years who were hospitalized on geriatric wards were included in this prospective analysis. A fifty-item frailty index (FI), a ten domain+co-morbidity frailty index based on a standardized comprehensive geriatric assessment (FI-CGA), the nine category Clinical Frailty Scale (CFS-9), the CSHA rules-based frailty definition (CSHA-RBFD), and the frailty phenotype (FP) were assessed during the patients' hospital stays. Patients were followed up over a one-year period. RESULTS: Follow-up data after one year could be obtained from 305 out of the 307 participants. Sixty two participants (20.3%) had died after that time. The FI, FI-CGA, CFS-9, CSHA-RBFD, and FP could all discriminate between patients who died and those who survived during follow-up (areas under the ROC curves: 0.805, 0.808, 0.852, 0.703 and 0.757, all P<0.001, respectively). The CFS-9 showed a better discriminative ability for one-year mortality compared to the FI, FI-CGA, CSHA-RBFD, and FP (all P<0.05, respectively). The FI and the FI-CGA did not differ in their discriminative ability for one-year mortality (P=0.440). The CSHA-RBFD and the FP demonstrated a comparable discriminative ability (P=0.241) and, when compared to the CFS-9, FI, and FI-CGA, an inferior discriminative ability for one-year mortality (all P<0.05, respectively). CONCLUSION: Among those frailty instruments that were evaluated, the CFS-9 emerged as the most powerful for prediction of one-year mortality. PMID- 27259030 TI - Hand tactile discrimination, social touch and frailty criteria in elderly people: A cross sectional observational study. AB - Frailty is a common syndrome among elderly and sensory decline may exacerbate functional decline. The hand function, the manual dexterity, the performance of the daily living skills and the social interactions are determined, in a large degree, by sensory integrity. However, hand tactile sensory deterioration has been little explored in frailty. We performed a cross sectional observational study with 181 of institutionalized elders. From the initial sample we selected 50 subjects (68-99 years) who met the inclusion/exclusion criteria. Our goals were (1) to analyse the relationship between tactile discrimination (TD) of the hand, avoidance behaviours and attitudes towards social touch (BATST) and phenotype frailty criteria (unintentional weight loss, self-perception of exhaustion, decrease grip strength - GS, slow walking speed, low level of physical activity), (2) to explore whether other variables can contribute to explain the differences between pre-frail and frail elders. The results showed that increasing age is related to decline of TD of the hand (p=0.021) and to decrease in GS (p=0.025); women have significantly lower level of GS (p=0.001); TD decrease is correlated with higher avoidance BATST (p=0.000) and with lower GS (p=0.000); Lower GS corresponds to more avoidance BATST (p=0.003). Hand TD also can differentiate frail and pre-frail elderly subjects in this sample (p=0.037). Decreased TD of the hand may have implications on the functionality and on interpersonal relationships. TD of the hand also explains frailty levels in this sample. Hand TD should be used in assessment and intervention protocols in pre frail and frail elders. PMID- 27259031 TI - Discovery of Novel 3-Quinoline Carboxamides as Potent, Selective, and Orally Bioavailable Inhibitors of Ataxia Telangiectasia Mutated (ATM) Kinase. AB - A novel series of 3-quinoline carboxamides has been discovered and optimized as selective inhibitors of the ataxia telangiectasia mutated (ATM) kinase. From a modestly potent HTS hit (4), we identified molecules such as 6-[6-(methoxymethyl) 3-pyridinyl]-4-{[(1R)-1-(tetrahydro-2H-pyran-4-yl)ethyl]amino}-3 quinolinecarboxamide (72) and 7-fluoro-6-[6-(methoxymethyl)pyridin-3-yl]-4-{[(1S) 1-(1-methyl-1H-pyrazol-3-yl)ethyl]amino}quinoline-3-carboxamide (74) as potent and highly selective ATM inhibitors with overall ADME properties suitable for oral administration. 72 and 74 constitute excellent oral tools to probe ATM inhibition in vivo. Efficacy in combination with the DSB-inducing agent irinotecan was observed in a disease relevant model. PMID- 27259036 TI - Influence of biochars, compost and iron grit, alone and in combination, on copper solubility and phytotoxicity in a Cu-contaminated soil from a wood preservation site. AB - Two biochars, a green waste compost and iron grit were used, alone and in combination, as amendment to improve soil properties and in situ stabilize Cu in a contaminated soil (964mgCukg(-1)) from a wood preservation site. The pot experiment consisted in 9 soil treatments (% w/w): untreated Cu-contaminated soil (Unt); Unt soil amended respectively with compost (5%, C), iron grit (1%, Z), pine bark-derived biochar (1%, PB), poultry-manure-derived biochar (1%, AB), PB or AB+C (5%, PBC and ABC), and PB or AB+Z (1%, PBZ and ABZ). After a 3-month reaction period, the soil pore water (SPW) was sampled in potted soils and dwarf beans were grown for a 2-week period. In the SPW, all amendments decreased the Cu(2+) concentration, but total Cu concentration increased in all AB-amended soils due to high dissolved organic matter (DOM) concentration. No treatment improved root and shoot DW yields, which even decreased in the ABC and ABZ treatments. The PBZ treatment decreased total Cu concentration in the SPW while reducing the gap with common values for root and shoot yields of dwarf bean plants. A field trial is underway before any recommendation for the PB-based treatments. PMID- 27259037 TI - High doses of ethylene diurea (EDU) are not toxic to willow and act as nitrogen fertilizer. AB - Ethylene diurea (EDU) is synthetic chemical which protects plants against damage caused by ground level O3 and is used experimentally as a biomonitoring tool at doses usually ranging from 200 to 400mgL(-1) a.i. Although several studies have investigated the protective action of EDU, this mechanism remains unclear. Important uncertainties in EDU action are whether EDU acts as a source of nitrogen (N) to plants and whether high doses are phytotoxic. In order to answer these questions, we conducted an open-field experiment where potted willow (Salix sachalinensis Fr. Schm) plants were exposed to ambient O3 conditions and treated with 0, 800 or 1600mgL(-1) EDU as a soil drench, every nine days, for about 2.5months. We examined approximately 50 response variables. Based on N content in different plant organs, we found that (a) all EDU was transferred to the leaves and (b) high doses of EDU increased the leaf N content. However, EDU did not affect the C content and distribution within the plant body. Still, even at the highest dose, EDU was not toxic to this fast-growing species (however such a high dose should not be applied in uncontrolled environments); and there was no EDU persistence in the soil, as indicated by soil N content. Notably, our soil was free from organic matter and N-poor. KEY MESSAGE: EDU per se does not cause toxicity to willow plants when applied as drench to a soil with no organic matter, rather, high EDU doses may act as nitrogen fertilizer in a nitrogen-poor soil. PMID- 27259032 TI - Multilaboratory evaluation of 15 bioassays for (eco)toxicity screening and hazard ranking of engineered nanomaterials: FP7 project NANOVALID. AB - Within EU FP7 project NANOVALID, the (eco)toxicity of 7 well-characterized engineered nanomaterials (NMs) was evaluated by 15 bioassays in 4 laboratories. The highest tested nominal concentration of NMs was 100 mg/l. The panel of the bioassays yielded the following toxicity order: Ag > ZnO > CuO > TiO2 > MWCNTs > SiO2 > Au. Ag, ZnO and CuO proved very toxic in the majority of assays, assumingly due to dissolution. The latter was supported by the parallel analysis of the toxicity of respective soluble metal salts. The most sensitive tests/species were Daphnia magna (towards Ag NMs, 24-h EC50 = 0.003 mg Ag/l), algae Raphidocelis subcapitata (ZnO and CuO, 72-h EC50 = 0.14 mg Zn/l and 0.7 mg Cu/l, respectively) and murine fibroblasts BALB/3T3 (CuO, 48-h EC50 = 0.7 mg Cu/l). MWCNTs showed toxicity only towards rat alveolar macrophages (EC50 = 15.3 mg/l) assumingly due to high aspect ratio and TiO2 towards R. subcapitata (EC50 = 6.8 mg Ti/l) due to agglomeration of TiO2 and entrapment of algal cells. Finally, we constructed a decision tree to select the bioassays for hazard ranking of NMs. For NM testing, we recommend a multitrophic suite of 4 in vitro (eco)toxicity assays: 48-h D. magna immobilization (OECD202), 72-h R. subcapitata growth inhibition (OECD201), 30-min Vibrio fischeri bioluminescence inhibition (ISO2010) and 48-h murine fibroblast BALB/3T3 neutral red uptake in vitro (OECD129) representing crustaceans, algae, bacteria and mammalian cells, respectively. Notably, our results showed that these assays, standardized for toxicity evaluation of "regular" chemicals, proved efficient also for shortlisting of hazardous NMs. Additional assays are recommended for immunotoxicity evaluation of high aspect ratio NMs (such as MWCNTs). PMID- 27259038 TI - Key challenges and priorities for modelling European grasslands under climate change. AB - Grassland-based ruminant production systems are integral to sustainable food production in Europe, converting plant materials indigestible to humans into nutritious food, while providing a range of environmental and cultural benefits. Climate change poses significant challenges for such systems, their productivity and the wider benefits they supply. In this context, grassland models have an important role in predicting and understanding the impacts of climate change on grassland systems, and assessing the efficacy of potential adaptation and mitigation strategies. In order to identify the key challenges for European grassland modelling under climate change, modellers and researchers from across Europe were consulted via workshop and questionnaire. Participants identified fifteen challenges and considered the current state of modelling and priorities for future research in relation to each. A review of literature was undertaken to corroborate and enrich the information provided during the horizon scanning activities. Challenges were in four categories relating to: 1) the direct and indirect effects of climate change on the sward 2) climate change effects on grassland systems outputs 3) mediation of climate change impacts by site, system and management and 4) cross-cutting methodological issues. While research priorities differed between challenges, an underlying theme was the need for accessible, shared inventories of models, approaches and data, as a resource for stakeholders and to stimulate new research. Developing grassland models to effectively support efforts to tackle climate change impacts, while increasing productivity and enhancing ecosystem services, will require engagement with stakeholders and policy-makers, as well as modellers and experimental researchers across many disciplines. The challenges and priorities identified are intended to be a resource 1) for grassland modellers and experimental researchers, to stimulate the development of new research directions and collaborative opportunities, and 2) for policy-makers involved in shaping the research agenda for European grassland modelling under climate change. PMID- 27259039 TI - Effective radium concentration in topsoils contaminated by lead and zinc smelters. AB - Trace elements (TE) are indicative of industrial pollution in soils, but geochemical methods are difficult to implement in contaminated sites with large numbers of samples. Therefore, measurement of soil magnetic susceptibility (MS) has been used to map TE pollutions, albeit with contrasted results in some cases. Effective radium concentration (ECRa), product of radium concentration by the emanation factor, can be measured in a cost-effective manner in the laboratory, and could then provide a useful addition. We evaluate this possibility using 186 topsoils sampled over about 783km(2) around two former lead and zinc smelters in Northern France. The ECRa values, obtained from 319 measurements, range from 0.70+/-0.06 to 12.53+/-0.49Bq.kg(-1), and are remarkably organized spatially, away from the smelters, in domains corresponding to geographical units. Lead contaminated soils, with lead concentrations above 100mg.kg(-1) <3km from the smelters, are characterized on average by larger peak ECRa values and larger dispersion. At large scales, away from the smelters, spatial variations of ECRa correlate well with spatial variations of MS, thus suggesting that, at distance larger than 5km, variability of MS contains a significant natural component. Larger ECRa values are correlated with larger fine fraction and, possibly, mercury concentration. While MS is enhanced in the vicinity of the smelters and is associated with the presence of soft ferrimagnetic minerals such as magnetite, it does not correlate systematically with metal concentrations. When multiple industrial and urban sources are present, ECRa mapping, thus, can help in identifying at least part of the natural spatial variability of MS. More generally, this study shows that ECRa mapping provides an independent and reliable assessment of the background spatial structure which underlies the structure of a given contamination. Furthermore, ECRa may provide a novel index to identify soils potentially able to fix leached components. PMID- 27259040 TI - Concentration Fluctuations and Capacitive Response in Dense Ionic Solutions. AB - We use molecular dynamics simulations in a constant potential ensemble to study the effects of solution composition on the electrochemical response of a double layer capacitor. We find that the capacitance first increases with ion concentration following its expected ideal solution behavior but decreases upon approaching a pure ionic liquid in agreement with recent experimental observations. The nonmonotonic behavior of the capacitance as a function of ion concentration results from the competition between the independent motion of solvated ions in the dilute regime and solvation fluctuations in the concentrated regime. Mirroring the capacitance, we find that the characteristic decay length of charge density correlations away from the electrode is also nonmonotonic. The correlation length first decreases with ion concentration as a result of better electrostatic screening but increases with ion concentration as a result of enhanced steric interactions. When charge fluctuations induced by correlated ion solvent fluctuations are large relative to those induced by the pure ionic liquid, such capacitive behavior is expected to be generic. PMID- 27259041 TI - A Methionine Residue Promotes Hyperoxidation of the Catalytic Cysteine of Mouse Methionine Sulfoxide Reductase A. AB - Methionine sulfoxide reductase A (msrA) reduces methionine sulfoxide in proteins back to methionine. Its catalytic cysteine (Cys72-SH) has a low pKa that facilitates oxidation by methionine sulfoxide to cysteine sulfenic acid. If the catalytic cycle proceeds efficiently, the sulfenic acid is reduced back to cysteine at the expense of thioredoxin. However, the sulfenic acid is vulnerable to "irreversible" oxidation to cysteine sulfinic acid that inactivates msrA (hyperoxidation). We observed that human msrA is resistant to hyperoxidation while mouse msrA is readily hyperoxidized by micromolar concentrations of hydrogen peroxide. We investigated the basis of this difference in susceptibility to hyperoxidation and established that it is controlled by the presence or absence of a Met residue in the carboxyl-terminal domain of the enzyme, Met229. This residue is Val in human msrA, and when it was mutated to Met, human msrA became sensitive to hyperoxidation. Conversely, mouse msrA was rendered insensitive to hyperoxidation when Met229 was mutated to Val or one of five other residues. Positioning of the methionine at residue 229 is not critical, as hyperoxidation occurred as long as the methionine was located within the group of 14 carboxyl-terminal residues. The carboxyl domain of msrA is known to be flexible and to have access to the active site, and Met residues are known to form stable, noncovalent bonds with aromatic residues through interaction of the sulfur atom with the aromatic ring. We propose that Met229 forms such a bond with Trp74 at the active site, preventing formation of a protective sulfenylamide with Cys72 sulfenic acid. As a consequence, the sulfenic acid is available for facile, irreversible oxidation to cysteine sulfinic acid. PMID- 27259042 TI - Parenting and mother-infant interactions in the context of maternal postpartum obsessive-compulsive disorder: Effects of obsessional symptoms and mood. AB - BACKGROUND: Maternal mental illness is associated with negative effects on the infant and child. Increased attention has been paid to the effects of specific perinatal disorders on parenting and interactions as an important mechanism of influence. OCD can be a debilitating disorder for the sufferer and those around them. Although OCD is a common perinatal illness, no previous studies have characterized parenting and mother infant interactions in detail for mothers with OCD. METHODS: 37 mothers with postpartum OCD and a 6 month old infant were compared with 37 community control dyads on a variety of measures of psychological distress and parenting. Observed mother-infant interactions were assessed independently. RESULTS: Obsessions and compulsions were reported in both groups, although they did not cause interference in the control group. Mothers with OCD were troubled by their symptoms for a mean of 9.6 hours/day. Mothers with OCD were less confident, reported more marital distress and less social support than healthy peers and were less likely to be breastfeeding. Infant temperament ratings did not differ. Mothers with OCD were rated as less sensitive in interactions than the comparison group, partly attributable to levels of concurrent depression. CONCLUSIONS: Maternal postpartum OCD is a disorder that can affect experiences of parenting and mother-infant interactions although this may not be driven by OCD symptoms. Longitudinal studies are required to assess the trajectory and impact of maternal difficulties as the infant develops. PMID- 27259043 TI - Human Enterovirus 71 Protein Displayed on the Surface of Saccharomyces cerevisiae as an Oral Vaccine. AB - Human enterovirus 71 (EV-A71), a major agent of hand, foot, and mouth disease, has become an important public health issue in recent years. No effective antiviral or vaccines against EV-A71 infection are currently available. EV-A71 infection intrudes bodies through the gastric mucosal surface and it is necessary to enhance mucosal immune response to protect children from these pathogens. Recently, the majority of EV-A71 vaccine candidates have been developed for parenteral immunization. However, parenteral vaccine candidates often induce poor mucosal responses. On the other hand, oral vaccines could induce effective mucosal and systemic immunity, and could be easily and safely administered. Thus, proper oral vaccines have attached more interest compared with parenteral vaccine. In this study, the major immunogenic capsid protein of EV-A71 was displayed on the surface of Saccharomyces cerevisiae. Oral immunization of mice with surface-displayed VP1 S. cerevisiae induced systemic humoral and mucosal immune responses, including virus-neutralizing titers, VP1-specific antibody, and the induction of Th1 immune responses in the spleen. Furthermore, oral immunization of mother mice with surface-displayed VP1 S. cerevisiae conferred protection to neonatal mice against the lethal EV-A71 infection. Furthermore, we observed that multiple boost immunization as well as higher immunization dosage could induce higher EV-A71-specific immune response. Our results demonstrated that surface-displayed VP1 S. cerevisiae could be used as potential oral vaccine against EV-A71 infection. PMID- 27259044 TI - Strategies for targeting residual HIV infection. PMID- 27259047 TI - Liver transplantation for hepatitis C virus in the era of direct-acting antiviral agents: Erratum. PMID- 27259045 TI - Tissue reservoirs of HIV. AB - PURPOSE OF REVIEW: Tissue reservoirs of HIV may promote the persistent immunopathology responsible for non-AIDS morbidity and data support multifocal reactivation from tissues as the source of viral rebound during antiretroviral therapy (ART) interruption. The heterogeneity of tissue reservoirs and incomplete knowledge about their composition are obstacles to an HIV cure. RECENT FINDINGS: In addition to the higher concentration of infected CD4 T cells found in both central lymphoid tissues and gut, specific subsets of CD4 T cells appear to play a disproportionate role in HIV persistence. Recently, a subset of central memory T cells enriched in lymph node germinal centers called T-follicular helper cells has been identified that expresses more viral RNA and occupies an anatomic niche inaccessible to cytotoxic T lymphocyte killing. Additional observations suggest that antiretroviral drug (ARV) concentrations may be lower in some tissues, raising the possibility for localized, low-level viral replication. Finally, some recent data implicate the persistence of infected, non-CD4 T-cell types in tissues during ART. SUMMARY: The retention of infected cells in a wide variety of tissues, often with distinct viral and cellular characteristics, underscores the importance of studying tissue reservoirs in the development and assessment of cure strategies. Both inhibitory ARVs and latency-reversing drugs must reach these sites, and novel strategies may be needed to attack virus in cells as variable as T-follicular helper cells and macrophages. PMID- 27259046 TI - Preclinical shock strategies to reactivate latent HIV-1: an update. AB - PURPOSE OF REVIEW: The 'shock and kill' strategy consists of activating HIV-1 expression to allow latently infected cells to die from viral cytopathic effects or host cytolytic immune effectors. This strategy relies on small molecules, called latency reversing agents, which activate HIV transcription. RECENT FINDINGS: Several mechanisms operating at the transcriptional level are involved in the establishment and maintenance of HIV-1 latency, including the absence of crucial inducible host transcription factors, epigenetic silencing, and the sequestration of the positive transcription elongation factor B. Progresses made toward the understanding of the molecular mechanisms of HIV-1 transcriptional repression have led to the identification of latency reversing agents that activate HIV transcription, such as histone deacetylase inhibitors or protein kinase C agonists. Multiple studies have recently pointed interesting ways to optimize the shock strategy by using combinations of latency reversing agents with an appropriate time schedule. SUMMARY: Combining latency reversing agents appears as one potential strategy for therapy against HIV-1 latency. PMID- 27259048 TI - Highly Repeatable and Recoverable Phototransistors Based on Multifunctional Channels of Photoactive CdS, Fast Charge Transporting ZnO, and Chemically Durable Al2O3 Layers. AB - Highly repeatable and recoverable phototransistors were explored using a "multifunctional channels" structure with multistacked chalcogenide and oxide semiconductors. These devices were made of (i) photoactive CdS (with a visible band gap), (ii) fast charge transporting ZnO (with a high field-effect mobility), and (iii) a protection layer of Al2O3 (with high chemical durability). The CdS TFT without the Al2O3 protection layer did not show a transfer curve due to the chemical damage that occurred on the ZnO layer during the chemical bath deposition (CBD) process used for CdS deposition. Alternatively, compared to CdS phototransistors with long recovery time and high hysteresis (DeltaVth = 19.5 V), our "multi-functional channels" phototransistors showed an extremely low hysteresis loop (DeltaVth = 0.5V) and superior photosensitivity with repeatable high photoresponsivity (52.9 A/W at 400 nm). These improvements are likely caused by the physical isolation of the sensing region and charge transport region by the insertion of the ultrathin Al2O3 layer. This approach successfully addresses some of the existing problems in CdS phototransistors, such as the high gate interface trap site density and high absorption of molecular oxygen, which originate from the polycrystalline CdS. PMID- 27259049 TI - Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. AB - Multiple acyl-CoA dehydrogenase deficiencies (MADDs) are a heterogeneous group of metabolic disorders with combined respiratory-chain deficiency and a neuromuscular phenotype. Despite recent advances in understanding the genetic basis of MADD, a number of cases remain unexplained. Here, we report clinically relevant variants in FLAD1, which encodes FAD synthase (FADS), as the cause of MADD and respiratory-chain dysfunction in nine individuals recruited from metabolic centers in six countries. In most individuals, we identified biallelic frameshift variants in the molybdopterin binding (MPTb) domain, located upstream of the FADS domain. Inasmuch as FADS is essential for cellular supply of FAD cofactors, the finding of biallelic frameshift variants was unexpected. Using RNA sequencing analysis combined with protein mass spectrometry, we discovered FLAD1 isoforms, which only encode the FADS domain. The existence of these isoforms might explain why affected individuals with biallelic FLAD1 frameshift variants still harbor substantial FADS activity. Another group of individuals with a milder phenotype responsive to riboflavin were shown to have single amino acid changes in the FADS domain. When produced in E. coli, these mutant FADS proteins resulted in impaired but detectable FADS activity; for one of the variant proteins, the addition of FAD significantly improved protein stability, arguing for a chaperone-like action similar to what has been reported in other riboflavin responsive inborn errors of metabolism. In conclusion, our studies identify FLAD1 variants as a cause of potentially treatable inborn errors of metabolism manifesting with MADD and shed light on the mechanisms by which FADS ensures cellular FAD homeostasis. PMID- 27259050 TI - Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L. AB - Ataxia-pancytopenia (AP) syndrome is characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to marrow failure and myeloid leukemia, sometimes associated with monosomy 7. Here, in the four-generation family UW-AP, linkage analysis revealed four regions that provided the maximal LOD scores possible, one of which was in a commonly microdeleted chromosome 7q region. Exome sequencing identified a missense mutation (c.2640C>A, p.His880Gln) in the sterile alpha motif domain containing 9-like gene (SAMD9L) that completely cosegregated with disease. By targeted sequencing of SAMD9L, we subsequently identified a different missense mutation (c.3587G>C, p.Cys1196Ser) in affected members of the first described family with AP syndrome, Li-AP. Neither variant is reported in the public databases, both affect highly conserved amino acid residues, and both are predicted to be damaging. With time in culture, lymphoblastic cell lines (LCLs) from two affected individuals in family UW-AP exhibited copy-neutral loss of heterozygosity for large portions of the long arm of chromosome 7, resulting in retention of only the wild-type SAMD9L allele. Newly established LCLs from both individuals demonstrated the same phenomenon. In addition, targeted capture and sequencing of SAMD9L in uncultured blood DNA from both individuals showed bias toward the wild-type allele. These observations indicate in vivo hematopoietic mosaicism. The hematopoietic cytopenias that characterize AP syndrome and the selective advantage for clones that have lost the mutant allele support the postulated role of SAMD9L in the regulation of cell proliferation. Furthermore, we show that AP syndrome is distinct from the dyskeratoses congenita telomeropathies, with which it shares some clinical characteristics. PMID- 27259052 TI - Fast and Accurate Construction of Confidence Intervals for Heritability. AB - Estimation of heritability is fundamental in genetic studies. Recently, heritability estimation using linear mixed models (LMMs) has gained popularity because these estimates can be obtained from unrelated individuals collected in genome-wide association studies. Typically, heritability estimation under LMMs uses the restricted maximum likelihood (REML) approach. Existing methods for the construction of confidence intervals and estimators of SEs for REML rely on asymptotic properties. However, these assumptions are often violated because of the bounded parameter space, statistical dependencies, and limited sample size, leading to biased estimates and inflated or deflated confidence intervals. Here, we show that the estimation of confidence intervals by state-of-the-art methods is inaccurate, especially when the true heritability is relatively low or relatively high. We further show that these inaccuracies occur in datasets including thousands of individuals. Such biases are present, for example, in estimates of heritability of gene expression in the Genotype-Tissue Expression project and of lipid profiles in the Ludwigshafen Risk and Cardiovascular Health study. We also show that often the probability that the genetic component is estimated as 0 is high even when the true heritability is bounded away from 0, emphasizing the need for accurate confidence intervals. We propose a computationally efficient method, ALBI (accurate LMM-based heritability bootstrap confidence intervals), for estimating the distribution of the heritability estimator and for constructing accurate confidence intervals. Our method can be used as an add-on to existing methods for estimating heritability and variance components, such as GCTA, FaST-LMM, GEMMA, or EMMAX. PMID- 27259051 TI - A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding. AB - A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer. PMID- 27259053 TI - Mutations in GANAB, Encoding the Glucosidase IIalpha Subunit, Cause Autosomal Dominant Polycystic Kidney and Liver Disease. AB - Autosomal-dominant polycystic kidney disease (ADPKD) is a common, progressive, adult-onset disease that is an important cause of end-stage renal disease (ESRD), which requires transplantation or dialysis. Mutations in PKD1 or PKD2 (~85% and ~15% of resolved cases, respectively) are the known causes of ADPKD. Extrarenal manifestations include an increased level of intracranial aneurysms and polycystic liver disease (PLD), which can be severe and associated with significant morbidity. Autosomal-dominant PLD (ADPLD) with no or very few renal cysts is a separate disorder caused by PRKCSH, SEC63, or LRP5 mutations. After screening, 7%-10% of ADPKD-affected and ~50% of ADPLD-affected families were genetically unresolved (GUR), suggesting further genetic heterogeneity of both disorders. Whole-exome sequencing of six GUR ADPKD-affected families identified one with a missense mutation in GANAB, encoding glucosidase II subunit alpha (GIIalpha). Because PRKCSH encodes GIIbeta, GANAB is a strong ADPKD and ADPLD candidate gene. Sanger screening of 321 additional GUR families identified eight further likely mutations (six truncating), and a total of 20 affected individuals were identified in seven ADPKD- and two ADPLD-affected families. The phenotype was mild PKD and variable, including severe, PLD. Analysis of GANAB-null cells showed an absolute requirement of GIIalpha for maturation and surface and ciliary localization of the ADPKD proteins (PC1 and PC2), and reduced mature PC1 was seen in GANAB(+/-) cells. PC1 surface localization in GANAB(-/-) cells was rescued by wild-type, but not mutant, GIIalpha. Overall, we show that GANAB mutations cause ADPKD and ADPLD and that the cystogenesis is most likely driven by defects in PC1 maturation. PMID- 27259054 TI - Mutations in TKT Are the Cause of a Syndrome Including Short Stature, Developmental Delay, and Congenital Heart Defects. AB - Whole-exome sequencing (WES) is increasingly being utilized to diagnose individuals with undiagnosed disorders. Developmental delay and short stature are common clinical indications for WES. We performed WES in three families, using proband-parent trios and two additional affected siblings. We identified a syndrome due to an autosomal-recessively inherited deficiency of transketolase, encoded by TKT, on chromosome 3p21. Our series includes three families with a total of five affected individuals, ranging in age from 4 to 25 years. Two families of Ashkenazi Jewish ancestry were homozygous for an 18 base pair in frame insertion in TKT. The third family was compound heterozygous for nonsense and missense variants in TKT. All affected individuals had short stature and were developmentally delayed. Congenital heart defects were noted in four of the five affected individuals, and there was a history of chronic diarrhea and cataracts in the older individuals with the homozygous 18 base pair insertion. Enzymatic testing confirmed significantly reduced transketolase activity. Elevated urinary excretion of erythritol, arabitol, ribitol, and pent(ul)ose-5-phosphates was detected, as well as elevated amounts of erythritol, arabitol, and ribitol in the plasma of affected individuals. Transketolase deficiency reduces NADPH synthesis and nucleic acid synthesis and cell division and could explain the problems with growth. NADPH is also critical for maintaining cerebral glutathione, which might contribute to the neurodevelopmental delays. Transketolase deficiency is one of a growing list of inborn errors of metabolism in the non-oxidative part of the pentose phosphate pathway. PMID- 27259056 TI - The Epidemiology of Leber Hereditary Optic Neuropathy in the North East of England. PMID- 27259055 TI - Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness. AB - By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(*)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(*)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium. PMID- 27259057 TI - Somatic Activating Mutations in GNAQ and GNA11 Are Associated with Congenital Hemangioma. PMID- 27259058 TI - Mutations in CAPN1 Cause Autosomal-Recessive Hereditary Spastic Paraplegia. PMID- 27259059 TI - Therapeutic Drug Monitoring, Electronic Health Records, and Pharmacokinetic Modeling to Evaluate Sirolimus Drug Exposure-Response Relationships in Renal Transplant Patients. AB - BACKGROUND: Sirolimus, an immunosuppressive agent used in renal transplantation, can prevent allograft rejection. Identification of the therapeutic index (the ratio of minimum toxic concentration to minimum therapeutic concentration) for immunosuppresants is necessary to optimize the care of patients and set standards for bioequivalence evaluation of sirolimus products. However, the therapeutic index for sirolimus has been inconsistently defined, potentially because of inconsistencies in sirolimus exposure-response relationships. METHODS: The authors used retrospective therapeutic drug monitoring data from the electronic health records of patients treated in a tertiary health care system from 2008 to 2014 to (1) develop a population pharmacokinetic (PK) model, (2) use the model to simulate sirolimus concentrations, and (3) characterize the exposure-response relationship. Using Wilcoxon rank-sum and Fisher exact tests, the authors determined relationships between sirolimus exposure and adverse events (AEs) (anemia, leukopenia, thrombocytopenia, hyperlipidemia, and decline in renal function) and the composite efficacy end point of graft loss or rejection. RESULTS: The developed 2-compartment population PK model showed appropriate goodness of fit. In a late-phase (>12 months), postrenal transplant population of 27 inpatients, the authors identified statistically significant relationships between 83 simulated peak and trough sirolimus concentrations and outcomes: graft loss or rejection (P = 0.018) and decline in renal function (P = 0.006), respectively. CONCLUSIONS: Use of therapeutic drug monitoring results and PK modeling permitted correlation of sirolimus concentrations with graft loss or rejection and decline in renal function. However, the method was limited in its assessment of other AEs. To better evaluate sirolimus exposure-response relationships, the method should be applied to a larger sample of newly transplanted patients with a higher propensity toward AEs or efficacy failure. PMID- 27259060 TI - Lithographically Encrypted Inverse Opals for Anti-Counterfeiting Applications. AB - Colloidal photonic crystals possess inimitable optical properties of iridescent structural colors and unique spectral shape, which render them useful for security materials. This work reports a novel method to encrypt graphical and spectral codes in polymeric inverse opals to provide advanced security. To accomplish this, this study prepares lithographically featured micropatterns on the top surface of hydrophobic inverse opals, which serve as shadow masks against the surface modification of air cavities to achieve hydrophilicity. The resultant inverse opals allow rapid infiltration of aqueous solution into the hydrophilic cavities while retaining air in the hydrophobic cavities. Therefore, the structural color of inverse opals is regioselectively red-shifted, disclosing the encrypted graphical codes. The decoded inverse opals also deliver unique reflectance spectral codes originated from two distinct regions. The combinatorial code composed of graphical and optical codes is revealed only when the aqueous solution agreed in advance is used for decoding. In addition, the encrypted inverse opals are chemically stable, providing invariant codes with high reproducibility. In addition, high mechanical stability enables the transfer of the films onto any surfaces. This novel encryption technology will provide a new opportunity in a wide range of security applications. PMID- 27259062 TI - Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders. AB - OBJECTIVE: Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory-relevant neuro circuits in this cohort. METHOD: Eighty-four patients with treatment-resistant unipolar depression who were moderately depressed or BD in remission were randomized to eight weekly EPO (40 000 IU) or saline infusions in a double-blind, parallel-group design. Participants underwent whole-brain fMRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall. RESULTS: Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity in dorsolateral prefrontal cortex (dlPFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dlPFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication. CONCLUSION: The findings highlight enhanced encoding-related dlPFC and temporo parietal activity as key neuronal underpinnings of EPO-associated memory improvement. PMID- 27259063 TI - Objective Outcomes of Supraglottoplasty for Children With Laryngomalacia and Obstructive Sleep Apnea: A Meta-analysis. AB - IMPORTANCE: Surgical intervention is the main treatment alternative for patients with severe laryngomalacia. Supraglottoplasty offers effective treatment results not only for laryngomalacia but also for concurrent obstructive sleep apnea (OSA). OBJECTIVE: To quantify the objective outcomes of supraglottoplasty for laryngomalacia with OSA via polysomnography data in the pediatric population. DATA SOURCES: A comprehensive literature search of the PubMed database was performed on May 20, 2015, using the search terms supraglottoplasty, epiglottoplasty, aryepiglottoplasty, laryngomalacia, obstructive sleep apnea, Apnea-Hypopnea Index (AHI), children, and polysomnography. There were no date restrictions. STUDY SELECTION: The literature search identified English-language studies that used polysomnography to evaluate patients with laryngomalacia and OSA after supraglottoplasty. Two reviewers screened titles and abstracts of the studies. The full texts of the studies were examined to assess their relevance to the meta-analysis. DATA EXTRACTION: Numerical polysomnography data were extracted and compared among studies where appropriate. A fixed- or random-effects model was used, when appropriate, to analyze the data and calculate effect sizes. RESULTS: Four studies were included in various subsets of the meta-analysis. After supraglottoplasty, the Apnea-Hypopnea Index (AHI) improved by a mean of 12.5 points in 4 studies (95% CI, -21.14 to -3.78; P = .005), oxygen saturation as measured by pulse oximetry nadir by 9.49 in 4 studies (95% CI, 4.87-14.12; P < .001), and Obstructive AHI by 21 points in 2 studies (95% CI, -50.3 to -8.29; P = .16). Twenty-nine of 33 children (88%) had residual disease. Patients 7 months and older had significant improvement in the AHI (P = .03). CONCLUSIONS AND RELEVANCE: Supraglottoplasty is an effective treatment modality for patients with laryngomalacia and OSA with objectively measurable benefits; however, patients will frequently have residual disease. Additional polysomnography after treatment is advised to ensure adequate resolution of the disorder. PMID- 27259064 TI - Recent advances of exosomes in immune modulation and autoimmune diseases. AB - Exosomes are small membrane-bound vesicles (30-100 nm) that are secreted by different types of cells and they have been well documented to resemble saucers or flattened spheres under the electron microscope. Recently, evidence indicates that exosomes play important roles in the immune modulation and are associated with the immune pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA), Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). In this review, we will summarize current research advances of exosomes in immunoregulation, pathogenesis, diagnosis and therapeutics of autoimmune diseases. PMID- 27259061 TI - Mathematical models of breast and ovarian cancers. AB - Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review, we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, as answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. WIREs Syst Biol Med 2016, 8:337-362. doi: 10.1002/wsbm.1343 For further resources related to this article, please visit the WIREs website. PMID- 27259065 TI - Evaluating the Performance of a New Model for Predicting the Growth of Clostridium perfringens in Cooked, Uncured Meat and Poultry Products under Isothermal, Heating, and Dynamically Cooling Conditions. AB - Clostridium perfringens type A is a significant public health threat and its spores may germinate, outgrow, and multiply during cooling of cooked meats. This study applies a new C. perfringens growth model in the USDA Integrated Pathogen Modeling Program-Dynamic Prediction (IPMP Dynamic Prediction) Dynamic Prediction to predict the growth from spores of C. perfringens in cooked uncured meat and poultry products using isothermal, dynamic heating, and cooling data reported in the literature. The residual errors of predictions (observation-prediction) are analyzed, and the root-mean-square error (RMSE) calculated. For isothermal and heating profiles, each data point in growth curves is compared. The mean residual errors (MRE) of predictions range from -0.40 to 0.02 Log colony forming units (CFU)/g, with a RMSE of approximately 0.6 Log CFU/g. For cooling, the end point predictions are conservative in nature, with an MRE of -1.16 Log CFU/g for single rate cooling and -0.66 Log CFU/g for dual-rate cooling. The RMSE is between 0.6 and 0.7 Log CFU/g. Compared with other models reported in the literature, this model makes more accurate and fail-safe predictions. For cooling, the percentage for accurate and fail-safe predictions is between 97.6% and 100%. Under criterion 1, the percentage of accurate predictions is 47.5% for single-rate cooling and 66.7% for dual-rate cooling, while the fail-dangerous predictions are between 0% and 2.4%. This study demonstrates that IPMP Dynamic Prediction can be used by food processors and regulatory agencies as a tool to predict the growth of C. perfringens in uncured cooked meats and evaluate the safety of cooked or heat treated uncured meat and poultry products exposed to cooling deviations or to develop customized cooling schedules. This study also demonstrates the need for more accurate data collection during cooling. PMID- 27259066 TI - Voxel-based morphometry in epileptic baboons: Parallels to human juvenile myoclonic epilepsy. AB - The epileptic baboon represents a natural model for genetic generalized epilepsy (GGE), closely resembling juvenile myoclonic epilepsy (JME). Due to functional neuroimaging and pathological differences between epileptic (SZ+) and asymptomatic control (CTL) baboons, we expected structural differences in gray matter concentration (GMC) using voxel-based morphometry (VBM). Standard anatomical (MP-RAGE) MRI scans using a 3T Siemens TIM Trio (Siemens, Erlangen, Germany) were available in 107 baboons (67 females; mean age 16+/-6years) with documented clinical histories and scalp-electroencephalography (EEG) results. For neuroimaging, baboons were anesthetized with isoflurane 1% (1-1.5 MAC) and paralyzed with vecuronium (0.1-0.3mg/kg). Data processing and analysis were performed using FSL's VBM toolbox. GMC was compared between CTL and SZ+ baboons, epileptic baboons with interictal epileptic discharges on scalp EEG (SZ+/IED+), asymptomatic baboons with abnormal EEGs (SZ-/IED+), and IED+ baboons with (IED+/PS+) and without (IED+/PS-) photosensitivity, and the subgroups amongst themselves. Age and gender related changes in gray matter volumes were also included as confound regressors in the VBM analyses of each animal group. Significant increases in GMC were noted in the SZ+/IED+ subgroup compared to the CTL group, including bilaterally in the frontopolar, orbitofrontal and anterolateral temporal cortices, while decreases in GMC were noted in the right more than left primary visual cortices and in the specific nuclei of the thalamus, including reticular, anterior and medial dorsal nuclei. No significant differences were noted otherwise, except that SZ+/IED+ baboons demonstrated increased GMC in the globus pallidae bilaterally compared to the SZ-/IED+ group. Similar to human studies of JME, the epileptic baboons demonstrated GMC decreases in the thalami and occipital cortices, suggesting secondary injury due to chronic epilepsy. Cortical GMC, on the other hand, was increased in the anterior frontal and temporal lobes, also consistent with human JME studies. This VBM study may indicate a combination of developmental and acquired structural changes in the epileptic baboon. PMID- 27259067 TI - Reduced expression of IA channels is associated with post-ischemic seizures. AB - PURPOSE: Post-stroke seizures are considered as a major cause of epilepsy in adults. The pathophysiologic mechanisms resulting in post-stroke seizures are not fully understood. The present study attempted to reveal a new mechanism underlying neuronal hyperexcitability responsible to the seizure development after ischemic stroke. METHODS: Transient global ischemia was produced in adult Wistar rats using the 4-vessel occlusion (4-VO) method. The spontaneous behavioral seizures were defined by the Racine scale III-V. The neuronal death in the brain was determined by hematoxylin-eosin staining. The expression levels of A-type potassium channels were analyzed by immunohistochemical staining and western blotting. RESULTS: We found that the incidence of spontaneous behavioral seizures increased according to the severity of ischemia with 0% after 15-min ischemia and ~50% after 25-min ischemia. All behavioral seizures occurred with 48h after ischemia. Morphological analysis indicated that brain damage was not correlated with behavioral seizures. Immunohistochemical staining showed that the expression levels of the A-type potassium channel subunit Kv4.2 was significantly reduced in ischemic brains with behavioral seizures, but not in ischemic brains without seizures. In addition, rats failing to develop spontaneous behavioral seizures within 2days after ischemia were more sensitive to bicuculline-induced seizures at 2 months after ischemia than control rats. Meanwhile, Kv4.2 expression was decreased in brain at 2 months after ischemia. CONCLUSION: Our results demonstrated the reduction of Kv4.2 expression might contribute to the development of post-ischemic seizures and long-term increased seizure susceptibility after ischemia. The mechanisms underlying post-stroke seizures and epilepsy is unknown so far. The down-regulation of IA channels may explained the abnormal neuronal hyperexcitability responsible for the seizure development after ischemic stroke. PMID- 27259068 TI - Susceptibility to seizure-induced sudden death in DBA/2 mice is altered by adenosine. AB - Sudden unexpected death in epilepsy (SUDEP) is rare but is an important public health burden due to the number of patient years lost. Respiratory dysfunction following generalized convulsive seizure is a common sequence of events in witnessed SUDEP cases. The DBA/2 mouse model of SUDEP exhibits generalized convulsive audiogenic seizures (AGSz), which result in seizure-induced respiratory arrest (S-IRA) in ~75% of these animals, while the remaining DBA/2 mice exhibit AGSz without S-IRA. SUDEP induction may involve actions of adenosine, which is released during generalized seizures in animals and patients and is known to depress respiration. This study examined the effects of systemic administration of agents that alter the actions of adenosine on the incidence of S-IRA in DBA/2 mice. DBA/2 mice that consistently exhibited AGSz without S-IRA showed a significantly increased incidence of S-IRA following treatment with 5 iodotubercidin, which blocks adenosine metabolism. Treatment of DBA/2 mice that consistently exhibited AGSz followed by S-IRA with a non-selective adenosine antagonist, caffeine, or an A2A adenosine receptor subtype-selective antagonist (SCH 442416) significantly reduced S-IRA incidence. By contrast, an A1 adenosine receptor antagonist (DPCPX) was not effective in reducing S-IRA incidence. These findings suggest that preventative approaches for SUDEP should consider agents that reduce the actions of adenosine. PMID- 27259070 TI - Grey matter anomalies in drug-naive childhood absence epilepsy: A voxel-based morphometry study with MRI at 3.0T. AB - BACKGROUND: Little is known, so far, about the cerebral structural abnormalities in drug-naive patients with childhood absence epilepsy (CAE). We aimed to investigate regional grey matter (GM) volume differences using voxel-based morphometry (VBM) in patients and closely matched healthy control subjects. METHODS: Twenty drug-naive patients diagnosed with CAE and 20 age- and gender matched healthy subjects were recruited. All participants underwent structural MRI scans with a 3.0T MR system. The differences in regional GM volumes between the two groups were determined by VBM analysis. Additional regression analyses were performed to identify any associations between regional GM volume and clinical seizure variables. RESULTS: Compared with controls, the patients with CAE showed less GM volume in the bilateral thalami. Furthermore, the GM volume in the bilateral thalami was negatively correlated with disease duration and age of onset in the CAE group. CONCLUSIONS: By excluding the potential effect of medication on brain structures, our study demonstrates less GM volume in the bilateral thalami in drug-naive patients with idiopathic CAE. Our study further provides structural neuroimaging evidence on the pathophysiology of absence seizures. PMID- 27259071 TI - Neonatal hyperbilirubinemia and the risk of febrile seizures and childhood epilepsy. AB - PURPOSE: The aim of the study was to estimate the association between newborn children treated with phototerapy for hyperbilirubinemia and the subsequent risk of febrile seizures or epilepsy in early childhood. METHODS: We conducted a follow-up study of singleton children (N=70 230) born between February 1998 and May 2003 from the Danish National Birth Cohort (DNBC). Information on exposure to phototherapy for hyperbilirubinemia was obtained from a questionnaire in the DNBC. Information on epilepsy and febrile seizures were obtained from the Danish National Hospital Registry (DNHR). Cox proportional hazard regression model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). RESULTS: Newborns treated with phototherapy for hyperbilirubinemia had a higher risk of developing epilepsy in early childhood (HR: 1.66, 95% CI: 1.23-2.24) but not febrile seizures (HR: 1.04, 95% CI: 0.86-1.27). The increases risk of epilepsy were only present for boys (HR: 1.98, 95% CI: 1.40-2.78) not for girls (HR: 1.14, 95% CI: 0.64-2.02) CONCLUSION: Phototherapy for hyperbilirubinemia in newborns was associated with an increased risk of epilepsy for males in early childhood. No excess risk was seen with febrile seizures. PMID- 27259069 TI - Rate and complications of adult epilepsy surgery in North America: Analysis of multiple databases. AB - Epilepsy surgery is under-utilized, but recent studies reach conflicting conclusions regarding whether epilepsy surgery rates are currently declining, increasing, or remaining steady. However, data in these prior studies are biased toward high-volume epilepsy centers, or originate from sources that do not disaggregate various procedure types. All major epilepsy surgery procedures were extracted from the Centers for Medicare and Medicaid Services Part B National Summary Data File and the American College of Surgeons National Surgical Quality Improvement Program. Procedure rates, trends, and complications were analyzed, and patient-level predictors of postoperative adverse events were identified. Between 2000-2013, 6200 cases of epilepsy surgery were identified. Temporal lobectomy was the most common procedure (59% of cases), and most did not utilize electrocorticography (63-64%). Neither temporal nor extratemporal lobe epilepsy surgery rates changed significantly during the study period, suggesting no change in utilization. Adverse events, including major and minor complications, occurred in 15.3% of temporal lobectomies and 55.6% of hemispherectomies. Our findings suggest stagnant rates of both temporal and extratemporal lobe epilepsy surgery across U.S. surgical centers over the past decade. This finding contrasts with prior reports suggesting a recent dramatic decline in temporal lobectomy rates at high-volume epilepsy centers. We also observed higher rates of adverse events when both low- and high-volume centers were examined together, as compared to reports from high-volume centers alone. This is consistent with the presence of a volume-outcome relationship in epilepsy surgery. PMID- 27259072 TI - Using a Visible Light-Polymerized Resin to Fabricate an Interim Partial Removable Dental Prosthesis. AB - An interim partial removable dental prosthesis (RDP) is any dental prosthesis that replaces some teeth in a partially dentate arch designed to enhance esthetics, stabilization, and/or function for a limited period of time, after which it is to be replaced by a definitive dental prosthesis. This article describes a technique that uses a visible light-polymerized (VLP) resin as the base material for an interim partial RDP. This technique can be easily accomplished in a dental office or laboratory and results in a predictable dental prosthesis. This technique eliminates the need for laboratory processing. PMID- 27259073 TI - Biochemical Characterization and Antimicrobial and Antifungal Activity of Two Endemic Varieties of Garlic (Allium sativum L.) of the Campania Region, Southern Italy. AB - Extracts of the bulbs of the two endemic varieties "Rosato" and "Caposele" of Allium sativum of the Campania region, Southern Italy, were analyzed. The phenolic content, ascorbic acid, allicin content, and in vitro antimicrobial and antifungal activity were determined. Ultra performance liquid chromatography with diode array detector performed polyphenol profile. The polyphenolic extracts showed antioxidant activity (EC50) lower than 120 mg. The amount of ascorbic acid and allicin in the two extracts was similar. Polyphenol extract exhibited antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and (only by the extract of Rosato) against Bacillus cereus. The extract of Caposele was more effective in inhibiting the growth of Aspergillus versicolor and Penicillum citrinum. On the other hand, the extract of Rosato was effective against Penicillium expansum. PMID- 27259074 TI - Common Use of Electroconvulsive Therapy for Chinese Adolescent Psychiatric Patients. AB - PURPOSE: Little is known about the use of electroconvulsive therapy (ECT) for adolescent psychiatric patients in China. This study examined the frequency of ECT and the demographic and clinical correlates of adolescent psychiatric patients hospitalized in a tertiary psychiatric hospital in China. METHODS: This was a retrospective chart review of 954 inpatients aged between 13 and 17 years treated over a period of 8 years (2007-2013). Sociodemographic and clinical data were collected from the electronic chart management system for discharged patients. RESULTS: The rate of ECT use was 42.6% in the whole sample (46.5% for patients with schizophrenia, 41.8% for major depressive disorder, 57.8% for bipolar disorders, and 23.9% for other diagnoses). Use of ECT was independently and positively associated with older age, high aggression risk at time of admission, and use of antipsychotics and antidepressants. Compared with patients with schizophrenia, those with other psychiatric diagnoses were less likely to receive ECT. The above significant correlates explained 32% of the variance of ECT use (P < 0.001). Limitations of this study included the lack of data regarding the efficacy and side effects of ECT. Furthermore, the high rate of ECT applied only to 1 setting which limits the ability to extrapolate the implications of the results to other populations. CONCLUSIONS: The use of ECT was exceedingly high in adolescent patients treated in a tertiary clinical centre in China. It is unlikely that such a high rate of ECT use is found across China or that such practice reflects standard of care for psychiatrically ill adolescents. The underlying reasons for the high use of ECT at this center warrant urgent investigations. PMID- 27259075 TI - Origin of Multiple Formula Use to Calculate Intraocular Lens Power-Reply. PMID- 27259076 TI - Iminium Catalysis inside a Self-Assembled Supramolecular Capsule: Modulation of Enantiomeric Excess. AB - The noncovalent combination of a supramolecular host with iminium organocatalysis is described. Due to cation-pi interactions the reactive iminium species is held inside the host and reacts in this confined environment. The products formed differ up to 92 % ee from the control experiments without added host. A model rationalizing the observed difference is presented. PMID- 27259077 TI - Contribution of gall microscopic structure to taxonomy of gallicolous aphids on Pistacia. AB - Aphids inducing galls on Pistacia plants belong to the tribe Fordini. According to the Heie & Wegierek classification, the genera are grouped into three subtribes. Previous microscopic studies showed that this taxonomy is not consistent with the histological characteristics of the galls. In this paper, galls induced by Aplonerura lentisci, Asiphonella cynodonti, Forda riccobonii, Slavun wertheimae and Smynthurodes betae were analyzed for the first time, as well as nine other galls previously described. Based on histological features three groups of galls can be establish: the first group comprises closed galls, induced by Baizongia pistaciae, Geoica utricularia, Rectinasus buxtoni and Slavun wertheimae; the second group includes two species of Geopemphigus (G. blackmani and G. torsus), and the third one is divided into two subgroups, the first comprises Aplonerura lentisci, Asiphonella cynodonti and Geopemphigus morral, and the second that includes Forda formicaria, F. marginata, F. riccobonii, Paracletus cimiciformis and Smynthurodes betae. An identification key of species based on microscopic features of galls is presented. PMID- 27259078 TI - Uptake of C14-atrazine by prairie grasses in a phytoremediation setting. AB - Agrochemicals significantly contribute to environmental pollution. In the USA, atrazine is a widely used pesticide and commonly found in rivers, water systems, and rural wells. Phytoremediation can be a cost-effective means of removing pesticides from soil. The objective of this project was to investigate the ability of prairie grasses to remove atrazine. 14C-labeled atrazine was added to sterilized sand and water/nutrient cultures, and the analysis was performed after 21 days. Switchgrass and big bluestem were promising species for phytoremediation, taking up about 40% of the applied [14C] in liquid hydroponic cultures, and between 20% and 33% in sand cultures. Yellow Indiangrass showed low resistance to atrazine toxicity and low uptake of [14C] atrazine in liquid hydroponic cultures. Atrazine degradation increased progressively from sand to roots and leaves. Most atrazine taken up by prairie grasses from sand culture was degraded to metabolites, which accounted for 60-80% of [14C] detected in leaves. Deisopropylatrazine (DIA) was the main metabolite detected in sand and roots, whereas in leaves further metabolism took place, forming increased amounts of didealkylatrazine (DDA) and an unidentified metabolite. In conclusion, prairie grasses achieved high atrazine removal and degradation, showing a high potential for phytoremediation. PMID- 27259079 TI - The relation between chronotype and treatment outcome with light therapy on a fixed time schedule. AB - BACKGROUND: Seasonal affective disorder (SAD) is characterized by recurrent episodes of major depression in a seasonal pattern. The therapy of choice is light therapy (LT). It is suggested that LT should be administered relative to the chronotype of the patient, with the optimal timing earlier for morning than for evening types. This study aims to retrospectively investigate the relation between chronotype and the effect of LT on a fixed time in the morning in a population of SAD patients. METHODS: Data from four different studies conducted at the University Center of Psychiatry in Groningen, the Netherlands was used. Data from 132 patients was used (103 women). Depression score was determined by a structured interview (SIGH-SAD) prior to LT and after LT. Prior to LT morningness/eveningness preference of the patient was determined by the 'Morningness/Eveningness Questionnaire' (MEQ). All patients received LT at 8:00 AM at the clinic, independent of chronotype. RESULTS: Patients had an average MEQ score of 51.5+/-8.2. There was no significant relationship between MEQ score and therapy success as measured with the SIGH-SAD (F2,129=0.05, ns). When patients were divided by chronotype (ranging from definite morning to moderate evening) no significant relation between MEQ score and therapy success was found (F2,129=0.02, ns). LIMITATIONS: Retrospective design. CONCLUSIONS: The lack of a significant relationship between chronotype, as measured with the MEQ, and therapy success with LT at a fixed timepoint may indicate that the anti depressive effect of morning light in SAD patients is not explained by a phase shift of the biological clock. PMID- 27259080 TI - Associations between poor subjective prenatal sleep quality and postnatal depression and anxiety symptoms. AB - BACKGROUND: Symptoms of depression and anxiety are common during pregnancy and the postnatal period. A risk factor for mood disorders is poor sleep quality. In this study we investigate the effects of poor subjective prenatal sleep quality on postnatal depressive and anxiety symptoms, independent of prenatal depression or anxiety, amongst pregnant women in the general population. METHODS: We analysed data from a subset of women taking part in a prospective cohort study, Growing Up in Singapore towards Healthy Outcomes. The participants completed the Edinburgh Postnatal Depression Scale and State-Trait Anxiety Inventory between 26 and 28 weeks of pregnancy (Time 1) and at 3 months postpartum (Time 2), and the Pittsburgh Sleep Quality Index at Time 1. Logistic regression analyses were used to investigate the associations between subjective prenatal sleep quality and postnatal depressive and anxiety symptoms, while adjusting for prenatal depressive/anxiety symptoms and education. RESULTS: Although borderline-high depressive/anxiety symptoms were the strongest predictors of postnatal depressive/anxiety, independent of this, poor subjective sleep quality during pregnancy was also associated with borderline-high postnatal depressive symptoms, but not with postnatal anxiety. LIMITATIONS: Sleep quality and prenatal/postnatal mood were derived from self-reported questionnaires, which may be more susceptible to bias. CONCLUSION: Although treatment of symptoms of prenatal depression and anxiety will be the most important for reducing postnatal depression and anxiety, in addition to that, future studies may explore treatments improving prenatal sleep quality, particularly for women with antenatal depressive symptoms. PMID- 27259081 TI - The natural course of elevated levels of depressive symptoms in patients with vascular disease over eight years of follow-up. The SMART-Medea study. AB - BACKGROUND: Patients with cardiovascular disease have an increased risk for depression, and depression predicts poor prognosis in these patients, but the long-term course of depression is not known. We studied the natural course of elevated levels of depressive symptoms in patients with cardiovascular disease over eight years follow-up. METHODS: Within the Second Manifestations of ARTerial disease - Memory, depression and aging (SMART-Medea) study, depressive symptoms were assessed with the Patient Health Questionnaire-9 (PHQ-9) in 690 patients (62+/-10 years) at baseline and bi-annually during 8 years follow-up. Natural course was described for symptom severity and course type (never, single episode, intermittent, and chronic) based on the cut-off point of >=6 on the PHQ-9. Using multinomial regression analysis (reference: never depressed) we estimated age- and sex-adjusted odds ratios (OR) for the associations of demographic factors and vascular disease categories with course type. RESULTS: Of the 690 patients, 60% was never depressed, 10% had a single episode, 19% had an intermittent and 11% a chronic course of depression. Increased risk for chronic course was observed for women (OR=3.42; 95% CI=1.98-5.90), those with younger age (OR=3.20; 95% CI=1.73 5.94), and for patients with cerebrovascular disease when compared to patients with coronary artery disease (OR=2.50; 95% CI=1.31-4.78). LIMITATIONS: No information was available on clinical diagnosed major depressive disorder and/or clinical events during follow-up. CONCLUSIONS: In patients with cardiovascular disease, an intermittent or chronic course of elevated levels of depressive symptoms is very common. Patients with cardiovascular disease may require more careful clinical monitoring and management of depressive symptoms. PMID- 27259083 TI - Responses of human sensory characteristics to 532 nm pulse laser stimuli. AB - BACKGROUND: Lasers are advantageous in some applications to stimulate a small target area and is used in various fields such as optogenetic, photoimmunological and neurophysiological studies. OBJECTIVE: This study aims to implement a non contact sense of touch without damaging biological tissues using laser. METHODS: Various laser parameters were utilized in safety range to induce a sense of touch and investigate the human responses. With heat distribution simulation, the amount of changes in the temperature and the tendency in laser parameters of sensory stimulation were analyzed. RESULTS: The results showed the identified tactile responses in safety range with various laser parameters and temperature distribution for the laser stimulus was obtained through the simulation. CONCLUSIONS: This study can be applied to the areas of sensory receptor stimulation, neurophysiology and clinical medicine. PMID- 27259082 TI - How should we screen for depression following a natural disaster? An ROC approach to post-disaster screening in adolescents and adults. AB - BACKGROUND: The present study's aim was to provide the foundation for an efficient, empirically based protocol for depression screening following a natural disaster. Utilizing a Receiver Operating Characteristic (ROC) analytic approach, the study tested a) what specific disaster-related stressors (i.e., property damage, loss of basic services) and individual-related constructs (i.e., PTSD symptoms, trauma history, social support) conveyed the greatest risk for post-natural disaster depression, b) specific cutoff scores across these measures, and c) whether the significance or cutoff scores for each construct varied between adolescents and adults. METHODS: Structured phone-based clinical interviews were conducted with 2000 adolescents who lived through a tornado and 1543 adults who survived a hurricane. RESULTS: Findings suggested that in both adolescents and adults, individual-related constructs forecasted greater risk for depressive symptoms following a natural disaster compared to disaster-related stressors. Furthermore, trauma history and PTSD symptoms were particularly strong indicators for adolescent depressive symptoms compared to adult depressive symptoms. Adolescents and adults who reported vulnerable scores for social support, trauma history, and lifetime PTSD symptoms were approximately twice as likely to present as depressed following the natural disaster. LIMITATIONS: Findings from the present study were limited to post-disaster assessments and based on self-reported functioning 6-12 months following the natural disaster. CONCLUSIONS: The present study synthesizes the extensive body of research on post disaster functioning by providing a clear framework for which questions may be most important to ask when screening for depression following a natural disaster. PMID- 27259084 TI - Evaluation of deformable image registration for contour propagation between CT and cone-beam CT images in adaptive head and neck radiotherapy. AB - Deformable image registration (DIR) is a critical technic in adaptive radiotherapy (ART) to propagate contours between planning computerized tomography (CT) images and treatment CT/Cone-beam CT (CBCT) image to account for organ deformation for treatment re-planning. To validate the ability and accuracy of DIR algorithms in organ at risk (OAR) contours mapping, seven intensity-based DIR strategies are tested on the planning CT and weekly CBCT images from six Head & Neck cancer patients who underwent a 6 ~ 7 weeks intensity-modulated radiation therapy (IMRT). Three similarity metrics, i.e. the Dice similarity coefficient (DSC), the percentage error (PE) and the Hausdorff distance (HD), are employed to measure the agreement between the propagated contours and the physician delineated ground truths. It is found that the performance of all the evaluated DIR algorithms declines as the treatment proceeds. No statistically significant performance difference is observed between different DIR algorithms (p> 0.05), except for the double force demons (DFD) which yields the worst result in terms of DSC and PE. For the metric HD, all the DIR algorithms behaved unsatisfactorily with no statistically significant performance difference (p= 0.273). These findings suggested that special care should be taken when utilizing the intensity based DIR algorithms involved in this study to deform OAR contours between CT and CBCT, especially for those organs with low contrast. PMID- 27259085 TI - Discrimination of motor imagery tasks via information flow pattern of brain connectivity. AB - BACKGROUND: The effective connectivity refers explicitly to the influence that one neural system exerts over another in frequency domain. To investigate the propagation of neuronal activity in certain frequency can help us reveal the mechanisms of information processing by brain. OBJECTIVE: This study investigates the detection of effective connectivity and analyzes the complex brain network connection mode associated with motor imagery (MI) tasks. METHODS: The effective connectivity among the primary motor area is firstly explored using partial directed coherence (PDC) combined with multivariate empirical mode decomposition (MEMD) based on electroencephalography (EEG) data. Then a new approach is proposed to analyze the connection mode of the complex brain network via the information flow pattern. RESULTS: Our results demonstrate that significant effective connectivity exists in the bilateral hemisphere during the tasks, regardless of the left-/right-hand MI tasks. Furthermore, the out-in rate results of the information flow reveal the existence of the contralateral lateralization. The classification performance of left-/right-hand MI tasks can be improved by careful selection of intrinsic mode functions (IMFs). CONCLUSION: The proposed method can provide efficient features for the detection of MI tasks and has great potential to be applied in brain computer interface (BCI). PMID- 27259086 TI - Assessment of cardiac time intervals by wavelet transform of the impedance cardiogram. AB - BACKGROUND: Impedance cardiography (ICG) is an inexpensive, noninvasive technique for estimating hemodynamic parameters. ICG can be used to obtain the ejection fraction of the left atrium and to monitor systolic time intervals. Traditional ICG technique does not enable unambiguous detection of the left ventricle ejection time (LVET) and the time relationships between specific marker points. OBJECTIVE: This work aims to approbate a new approach for ICG signal processing using wavelet transform (WT) and to investigate the possibilities of this approach for determination of the parameters which are related to the stroke volume (SV), in particular LVET. METHODS: Thoracic tetrapolar polyrheocardiography method for simultaneous registration of ECG, ICG and phonocardiograms has been used. A control group consisted of eight healthy men aged 20-25 years. In addition, four patients with essential hypertension participated in the study. Wavelet representation of the ICG data produced local maxima in a two dimensional distribution of the wavelet coefficient. Each extremum point was characterized by the amplitude, scale and time, which determine SV. RESULTS: LVET was defined as the scale corresponding to the E-wave maximum related to the systolic phase of the cardiac cycle. Also, we defined the initial systolic time interval (ISTI) as the time interval between R peak in the ECG and E-wave maximum on the wavelet plane. During functional test LVET and ISTI values defined by WT demonstrated a proper hemodynamic response to loading for the control group and patients with essential hypertension. CONCLUSION: The proposed approach demonstrates the ability of ICG-WT technique for adequate assessment of SV parameters, including cardiac time intervals. PMID- 27259087 TI - Mid-term outcomes after radiofrequency-targeted vertebral augmentation in the treatment of myeloma associated vertebral fractures. AB - BACKGROUND: Myeloma patients often suffer from painful vertebral fractures (VCF) which impair their quality of life. Common methods for augmentation of the vertebrae are vertebroplasty, kyphoplasty and radiofrequency-targeted vertebral augmentation (RF-TVA). OBJECTIVE: This study evaluates the long-term effectiveness and safety of RF-TVA in the treatment of myeloma associated VCF. METHODS: Eighty-seven myeloma patients (mean age: 64.7 +/- 9.5 years) with VCF were treated with RF-TVA. Patient data were assessed preoperatively and in five postoperative examinations up to 12 months. Pain was measured with the visual analogue scale (VAS) and the impairment was evaluated with the Oswestry Disability-Index (ODI) at each examination. In addition, the mid vertebral height, kyphosis angle, and additional fractures were evaluated by x-rays. Furthermore, cement leakage was documented. RESULTS: The VAS values were significantly improved in comparison to the preoperative values (p<= 0.001), but slightly fluctuating during the follow-up period. The ODI was also significantly improved (p<= 0.001), but it showed a worsening from the 12 months evaluation to the 24 months evaluation. The kyphosis angle and the vertebral height were significantly improved after surgery (p = 0.03, p <= 0.001), but worsened steadily to the last follow up examination. Cement leakage was asymptomatic and occurred in 18% of the patients. In 10% of the patients additional fractures were detected in the 24 months evaluation. CONCLUSIONS: The results of our study show that RF-TVA is a safe treatment for myeloma associated vertebral compression fractures, which achieves an acceptable improvement of patient's pain and quality of life. PMID- 27259088 TI - Hip arthroscopy for excision of osteoid osteoma and for the application of a collagen cartilage implant: Case report in a professional athlete, and literature review. AB - BACKGROUND: Osteoid osteoma is an osteoblastic benign bone tumor usually affecting young adolescents. Intra-articular lesions are not common; usually the diagnosis is delayed. A lot of studies report difficulties and complications in the management of osteoid osteoma of the hip joint using imaging guided techniques or open surgical procedures. Only few published cases have described that it can be treated precisely using hip arthroscopy. Additionally, the use of hip arthroscopy to apply the Chondrofiller(r), an acellular collagen matrix for the management of articular cartilage defects of the hip joint, has not yet been described. CASE PRESENTATION: This report presents an osteoid osteoma of the femoral neck. A 20-year-old female professional basketball player presented with pain in the left groin since more than 12 months. On magnetic resonance and computed tomography imaging, an osteoid osteoma was suggested. The lesion was successfully removed using arthroscopy. During surgery, a concomitant grade 4 cartilage lesion on the femoral head was detected. For the treatment of this severe defect we used the Chondrofiller(r), which is a new acellular collagen implant for auto-regeneration of articular cartilage. This matrix was filled into the prepared and dried defect using CO2 arthroscopy. After the hardening of the matrix the surgery was finished. The patient was pain free shortly after the operation and returned to sports within 16 weeks. Return to high-performance sports 8 months after surgery was without of any sign of complaints. CONCLUSIONS: This article demonstrates that hip arthroscopy is a valuable tool for biopsy and excision of intra-articular osteoid osteoma affecting the hip joint, as well as for addressing other concomitant pathologies such as a severe synovitis or cartilage defects. CO2 arthroscopy provided good conditions for the drying and filling of the cartilage defect with the Chondrofiller(r). PMID- 27259090 TI - Enhancing Aerobic Exercise with a Novel Virtual Exercise Buddy Based on the Kohler Effect. AB - OBJECTIVE: Research on active videogames (AVGs) has demonstrated the motivation boosting power of the Kohler effect (a motivating force for "weak links" in groups based on group principles of upward social comparison and indispensability) with software-generated partners (SGPs), but the effect has yet to be examined over time. We tested the viability of the Kohler effect in an AVG with an SGP over 12 exercise sessions using a cycle ergometer and whether a fatiguing partner (FP) could further boost the effect. MATERIALS AND METHODS: A repeated-measures design was used to assess mean changes in exercise persistence over time. Participants were randomly assigned to one of three game conditions: AVG alone (individual-control [IC]), AVG with a consistently superior partner (CSP), or AVG with a superior partner who showed signs of fatigue (FP). Assessments were conducted on 82 participants (42 college students and 40 adults from the community) in a laboratory over 12 experimental sessions. The main outcome measure was exercise persistence (minutes of gameplay cycling at 75% HRmax). RESULTS: Data yielded significant improvements in exercise duration for men in the FP condition when compared with men in the IC condition (Mdiff = 12:32 minutes, SEdiff = 4:54). Women showed no change in exercise persistence over time and no condition differences. CONCLUSION: Exercising in an AVG with a superior SGP, who shows signs of fatigue over time, improved exercise persistence for men but not for women under present experimental conditions. PMID- 27259089 TI - Procedural outcomes with use of the flash ostial system in aorto-coronary ostial lesions. AB - BACKGROUND: The Flash Ostial system (Ostial Corporation, Sunnyvale, CA) was designed to optimize implantation of aorto-ostial coronary stents by flaring the proximal stent struts against the aortic wall. METHODS: We retrospectively reviewed the medical record, angiograms, and intravascular ultrasound images of 22 aorto-ostial percutaneous coronary interventions performed at our institution between March and September 2015. The Flash Ostial system was used in 13 cases (59%). RESULTS: Mean age was 67 +/- 8 years and all patients were men. The target vessel was the right coronary artery (59%), left main (27%), or a saphenous vein graft (14%); 59% of the lesions had moderate/severe calcification. The mean number of predilation balloons was 1.8 +/- 1.6, mean Flash ostial balloon diameter was 3.3 +/- 0.5 mm and mean inflation pressure was 13.1 +/- 4.0 atmospheres. Intravascular ultrasonography (available for 19 patients) revealed mean ostial minimum lumen cross-sectional area (MLA) of 9.2 +/- 3.0 mm2 and reference MLA of 8.5 +/- 2.7 mm2 . The percent difference between ostial and reference MLA was higher in cases in which the Flash Ostial system was used versus those where it was not (9.6 +/- 5.5% vs. 4.0 +/- 2.8%, P = 0.03). All stent struts were well apposed. Technical success was 100%. One patient developed a left groin pseudoaneurysm treated with thrombin injection and one patient had a periprocedural myocardial infarction. Median contrast, fluoroscopy time, and procedure time were 235 mL, 33 min, and 118 min, respectively. CONCLUSIONS: The Flash Ostial system can be successfully used in aorto-ostial stenting, resulting in large ostial vessel MLA. (c) 2016 Wiley Periodicals, Inc. PMID- 27259091 TI - Piezotronic Effect Modulated Heterojunction Electron Gas in AlGaN/AlN/GaN Heterostructure Microwire. AB - The piezotronic effect is applied to modulate the physical properties of heterojunction electron gas and thus tune the electric transport in AlGaN/AlN/GaN heterostructure microwires. At room temperature, the conductance is increased by 165% under -1.78% compressive strains, and reduced by 48% under 1.78% tensile strains; at 77 K, this modulating effect is further improved by 890% and 940% under compressive and tensile strains, respectively. PMID- 27259092 TI - Local anaesthetic wound infiltration for postcaesarean section analgesia: A systematic review and meta-analysis. AB - BACKGROUND: Wound infiltration with local anaesthetics has been investigated as a potentially useful method for providing analgesia after caesarean delivery, but the literature is inconclusive. OBJECTIVE: The objective is to assess the efficacy of local anaesthetic wound infiltration in reducing pain scores and opioid consumption in women undergoing caesarean delivery. DESIGN: Systematic review of randomised controlled trials with meta-analyses. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled trials (CENTRAL) until December 2015. ELIGIBILITY CRITERIA: Randomised controlled trials that assessed the efficacy of local anaesthetic wound infiltration using an infusion or single injection technique for postcaesarean section analgesia. RESULTS: A total of 21 studies were included in the final analysis (11 studies using an infusion technique and 10 studies using single infiltration). Local anaesthetic wound infiltration significantly decreased opioid consumption at 24 h [mean difference -9.69 mg morphine equivalents, 95% confidence interval (CI), -14.85 to -4.52] and pain scores after 24 h at rest (mean difference -0.36, 95% CI, -0.58 to -0.14) and on movement (mean difference -0.61, 95% CI, -1.19 to -0.03). Subgroup analysis did not suggest a difference in primary outcomes between infusions and single infiltration. Opioid consumption was reduced in patients who did not receive intrathecal morphine but not in those who received intrathecal morphine, although there were very little data in patients receiving intrathecal morphine. Pain scores at rest and on movement at 24 h were reduced with catheter placement below the fascia but not above the fascia. There were no statistically significant reductions in nausea, vomiting or pruritus with local anaesthetic infiltration. CONCLUSION: Local anaesthetic wound infiltration reduces postoperative opioid consumption but had minimal effect on pain scores and did not reduce opioid-related side-effects in women who had undergone delivery by caesarean section. The review is limited by a paucity of studies using intrathecal morphine and by the indirect comparisons performed for subgroup analyses. PMID- 27259093 TI - Rhabdomyolysis and acute kidney injury: creatine kinase as a prognostic marker and validation of the McMahon Score in a 10-year cohort: A retrospective observational evaluation. AB - BACKGROUND: High-volume fluid resuscitation and the administration of sodium bicarbonate and diuretics have a theoretical renoprotective role in patients at high risk of acute kidney injury (AKI) following rhabdomyolysis. Abnormally elevated creatine kinase has previously been used as a biological marker for the identification of patients at high risk of AKI following rhabdomyolysis. OBJECTIVE: To assess the sensitivity and specificity of plasma creatine kinase (admission and peak values) for the prediction of AKI requiring renal replacement therapy (RRT) or of death in patients with confirmed rhabdomyolysis. To compare the diagnostic performance of creatine kinase with the McMahon score. DESIGN: Retrospective observational study. Data collection included McMahon and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores; daily creatine kinase; daily creatinine and electrolytes; ICU length of stay and mortality. SETTING: Neurosciences and Trauma Critical Care Unit (Cambridge, UK). PATIENTS: In total, 232 adults with confirmed rhabdomyolysis (creatine kinase > 1000 Ul) admitted to Neurosciences and Trauma Critical Care Unit between 2002 and 2012. MAIN OUTCOME MEASURES: AKI, RRT and mortality. RESULTS: Forty-five (19%) patients developed AKI and 29 (12.5%) patients required RRT. Mortality was significantly higher in patients who developed AKI (62 vs. 18%, P < 0.001). Average creatine kinase on admission was 5009 (range 69-157 860) Ul. Creatine kinase peaked between the day of admission and day 3 in 91% of cases. PEAK creatine kinase of at least 5000 Ul is 55% specific and 83% sensitive for the prediction of AKI requiring RRT. A McMahon Score of at least 6 calculated on admission is 68% specific and 86% sensitive for RRT. CONCLUSIONS: Creatine kinase is not a specific or early predictor of AKI in patients with rhabdomyolysis. Although a PEAK creatine kinase of at least 5000 Ul has sensitivity acceptable for screening purposes, this is often a delayed finding. A McMahon score of at least 6 calculated on admission allows for a more sensitive, specific and timely identification of patients who may benefit from high-volume fluid resuscitation. PMID- 27259094 TI - Determination of a cut-off value of antral area measured in the supine position for the fast diagnosis of an empty stomach in the parturient: A prospective cohort study. AB - BACKGROUND: Ultrasound measurement of the antral cross-sectional area of the stomach, performed in the supine position, has been described for preoperative assessment of gastric content in the adult, but, to date, no study has determined the cut-off value of the antral area for the diagnosis of an empty stomach in the parturient. Nevertheless, previous studies in parturients have reported that the use of a simple qualitative grading scale (0 to 2) was reliable for the estimation of the gastric fluid volume. However, this qualitative grading score requires turning the parturient into the right lateral decubitus position for the ultrasound examination, something which may not be easily feasible, particularly in the case of an obstetric emergency. OBJECTIVE: To calculate the cut-off value of the antral area, measured in the supine position during established labour, for the diagnosis of 'empty' stomach. DESIGN: A prospective cohort study. SETTING: Hospices Civils de Lyon, Hopital Femme Mere Enfant, Lyon, France. PATIENTS: Seventy-three women in established labour. INTERVENTIONS: For each parturient, ultrasound assessment of gastric contents was performed in the supine and right lateral decubitus position and scored 0 to 3 on a qualitative grading scale. This assessment was followed by ultrasound measurement of the antral cross sectional area in both the supine and right lateral positions. MAIN OUTCOME MEASURES: To assess the performance of the antral area measured in the supine position for the diagnosis of an 'empty' stomach (gastric antrum grade 0), a receiver operating characteristic curve was plotted, and the area under the receiver operating characteristic curve was calculated. RESULTS: Data from 73 women were analysed. For the diagnosis of grade 0, the cut-off value for the antral area measured in the supine position was 381 mm (sensitivity, 81%; specificity, 76% and negative predictive value, 80%). CONCLUSION: With a parturient lying in the supine position, a single assessment of the antral cross sectional area may be used for the fast diagnosis of an empty stomach. This tool could be useful in assessing the risk of aspiration for parturients who require emergency anaesthesia during labour. PMID- 27259095 TI - Identification of ROS Produced by Nanobubbles and Their Positive and Negative Effects on Vegetable Seed Germination. AB - Exogenous reactive oxygen species (ROS) produced by nanobubble (NB) water offer a reasonable explanation for NBs' physiological promotion and oxidation effects. To develop and exploit the NB technology, we have performed further research to identify the specific ROS produced by NBs. Using a fluorescent reagent APF, a Fenton reaction, a dismutation reaction of superoxide dismutase and DMSO, we distinguished four types of ROS (superoxide anion radical (O2.-), hydrogen peroxide (H2O2), hydroxyl radical (.OH), and singlet oxygen (1O2)). .OH was confirmed to be the specific ROS produced by NB water. The role of .OH produced by NB water in physiological processes depends on its concentration. The amount of exogenous .OH has a positive correlation with the NB number density in the water. Here, spinach and carrot seed germination tests were repeatedly performed with three seed groups submerged in distilled water, high-number density NB water, and low-number density NB water under similar dissolved oxygen concentrations. The final germination rates of spinach seeds in distilled water, low-number density NB water, and high-number density NB water were 54%, 65%, and 69%, respectively. NBs can also promote sprout growth. The sprout lengths of spinach seeds dipped in NB water were longer than those in the distilled water. For carrot seeds, the amount of exogenous .OH in high-number density NB water was beyond their toxic threshold, and negative effects were shown on hypocotyl elongation and chlorophyll formation. The presented results allow us to obtain a deeper understanding of the physiological promotion effects of NBs. PMID- 27259097 TI - Copper-Catalyzed Coupling of 2-Siloxy-1-alkenes and Diazocarbonyl Compounds: Approach to Multisubstituted Furans, Pyrroles, and Thiophenes. AB - We report herein copper(II)-catalyzed cyclization reactions of silyl enol ethers derived from methyl ketones with alpha-diazo-beta-ketoesters or alpha diazoketones to afford 2-siloxy-2,3-dihydrofuran derivatives or 2,3,5 trisubstituted furans, respectively, under mild conditions. The former cyclization products serve as versatile 1,4-diketone surrogates, allowing facile preparation of 2,3,5-trisubstituted furans, pyrroles, and thiophenes. PMID- 27259096 TI - Lymphatic Function in the Early Postoperative Period of Breast Cancer Has No Short-Term Clinical Impact. AB - OBJECTIVE: To evaluate by lymphoscintigraphy the lymphatic function in the preoperative period up to 2 months after surgery for breast cancer, and the relationship between the lymphatic function with clinical features and physical complications. METHODS: One hundred and five women were studied before and 2 months after surgery to treat breast cancer. On each occasion, inspection and palpation of surgical wound, upper limb circumference, and lymphoscintigraphy were performed. Lymphatic function analysis consisted of velocity of axillary lymph node (LN) visualization; intensity of LN uptake; collateral circulation; dermal backflow; and hepatic uptake. RESULTS: In the postoperative period, there was a significant worsening of the degree of LN uptake (p = 0.0003) and in the velocity of LN visualization (p = 0.01). No significant differences in dermal backflow (p = 0.4) and collateral circulation (p = 0,07) were observed. There was a significant increase in liver absorption (p = 0.0002). 37.1% of the patients developed seroma, 11.2% dehiscence, and 25.8% infection. No relationship was found between lymphoscintigraphy changes and postoperative complications or clinical characteristics. CONCLUSION: Lymphoscintigraphy, performed 60 days post surgery for breast cancer, can detect a worsening in lymphatic drainage and some sign of lymphatic changes. These changes are not related to clinical characteristics and physical complications. PMID- 27259098 TI - 'Everything's neatly tucked away': young women's views on desirable vulval anatomy. AB - In the context of rapidly increasing requests for female genital cosmetic surgery (FGCS) and a lack of published research in this area, we explored young women's knowledge of vulval anatomy and sources of anatomical information. We conducted 21 semi-structured interviews with young women aged 18-28 years at an Australian tertiary institution. Interviews explored participants' knowledge of 'normal' and 'ideal' genital anatomy and how these perceptions were formed. Interviews were recorded, transcribed and analysis identified 6 major themes and 30 sub-themes. We found that many women were unsure what constitutes normal genital anatomy. Few women knew to which parts the word vulva refers. All participants identified a photograph of hairless female genitals with no visible labia minora as the societal 'ideal', and all strongly agreed on the need for appropriate educational resources. Young women would benefit from access to resources showing the normal range of genital anatomy. Results suggest that doctors receiving requests for FGCS should explore women's understanding of their anatomy and what they believe the surgery will achieve. Some young women may simply need reassurance of their normality. Findings from this study may contribute to educational material for both health professionals and young people. PMID- 27259099 TI - Low-Volume High-Intensity Interval Training as a Therapy for Type 2 Diabetes. AB - Our purpose was to investigate the effects of low-volume, high-intensity interval training (HIT) on cardiometabolic risk and exercise capacity in women with type 2 diabetes mellitus (T2DM). Sedentary overweight/obese T2DM women (age=44.5+/-1.8 years; BMI=30.5+/-0.6 kg/m(2)) were randomly assigned to a tri-weekly running based HIT program (n=13) or non-exercise control follow-up (CON; n=10). Glycemic control, lipid and blood pressure levels, endurance performance, and anthropometry were measured before and after the follow-up (16 weeks) in both groups. Medication intake was also assessed throughout the follow-up. Improvements (P<0.05) on fasting glucose (14.3+/-1.4%), HbA1c (12.8+/-1.1%), systolic blood pressure (3.7+/-0.5 mmHg), HDL-cholesterol (21.1+/-2.8%), triglycerides (17.7+/-2.8%), endurance performance (9.8+/-1.0%), body weight (2.2+/-0.3%), BMI (2.1+/-0.3%), waist circumference (4.0+/-0.5%) and subcutaneous fat (18.6+/-1.4%) were found after HIT intervention. Patients of HIT group also showed reductions in daily dosage of antihyperglycemic and antihypertensive medication during follow-up. No changes were found in any variable of CON group. The HIT-induced improvements occurred with a weekly time commitment 56-25% lower than the minimal recommended in current guidelines. These findings suggest that low-volume HIT may be a time-efficient intervention to treat T2DM women. PMID- 27259100 TI - Proposal and validation of a new model to estimate survival for hepatocellular carcinoma patients. AB - BACKGROUND AND AIMS: The survival of hepatocellular carcinoma (HCC) patients is heterogeneous. We aim to develop and validate a simple prognostic model to estimate survival for HCC patients (MESH score). METHODS: A total of 3182 patients were randomised into derivation and validation cohort. Multivariate analysis was used to identify independent predictors of survival in the derivation cohort. The validation cohort was employed to examine the prognostic capabilities. RESULTS: The MESH score allocated 1 point for each of the following parameters: large tumour (beyond Milan criteria), presence of vascular invasion or metastasis, Child-Turcotte-Pugh score >=6, performance status >=2, serum alpha fetoprotein level >=20 ng/ml, and serum alkaline phosphatase >=200 IU/L, with a maximal of 6 points. In the validation cohort, significant survival differences were found across all MESH scores from 0 to 6 (all p < 0.01). The MESH system was associated with the highest homogeneity and lowest corrected Akaike information criterion compared with Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer (HKLC), Cancer of the Liver Italian Program, Taipei Integrated Scoring and model to estimate survival in ambulatory HCC Patients systems. The prognostic accuracy of the MESH scores remained constant in patients with hepatitis B- or hepatitis C related HCC. The MESH score can also discriminate survival for patients from early to advanced stages of HCC. CONCLUSIONS: This newly proposed simple and accurate survival model provides enhanced prognostic accuracy for HCC. The MESH system is a useful supplement to the BCLC and HKLC classification schemes in refining treatment strategies. PMID- 27259101 TI - Chemical Synthesis of Human Insulin-Like Peptide-6. AB - Human insulin-like peptide-6 (INSL-6) belongs to the insulin superfamily and shares the distinctive disulfide bond configuration of human insulin. In this report we present the first chemical synthesis of INSL-6 utilizing fluorenylmethyloxycarbonyl-based (Fmoc) solid-phase peptide chemistry and regioselective disulfide bond construction protocols. Due to the presence of an oxidation-sensitive tryptophan residue, two new orthogonal synthetic methodologies were developed. The first method involved the identification of an additive to suppress the oxidation of tryptophan during iodine-mediated S acetamidomethyl (Acm) deprotection and the second utilized iodine-free, sulfoxide directed disulfide bond formation. The methodologies presented here offer an efficient synthetic route to INSL-6 and will further improve synthetic access to other multiple-disulfide-containing peptides with oxidation-sensitive residues. PMID- 27259116 TI - Escherichia coli MazEF toxin-antitoxin system does not mediate programmed cell death. AB - Toxin-antitoxins systems (TAS) are prokaryotic operons containing two small overlapping genes which encode two components referred to as toxin and antitoxin. Involvement of TAS in bacterial programmed cell death (PCD) is highly controversial. MazEF, a typical type II TAS, is particularly implicated in mediating PCD in Escherichia coli. Hence, we compared the metabolic fitness and stress tolerance of E. coli strains (MC4100 and its mazEF-derivative) which were extensively used by proponents of mazEF-mediated PCD. We found that both the strains are deficient in relA gene and that the DeltamazEF strain has lower fitness and stress tolerance compared to wild type MC4100. We could not reproduce mazEF mediated PCD which emphasizes the need for skeptic approach to the PCD hypothesis. PMID- 27259118 TI - Characterization of the geometry of microscale periodic structures using acoustic microscopy. AB - Periodic structures are very common in both scientific investigations and engineering applications. The geometry of the periodic structure is important for its designed functionality. Although the techniques such as optical and electron microscopy are capable of measuring the periodicity of microscale periodically corrugated structures, they cannot be used to measure the height or depth of the corrugation. The technique of acoustic microscopy has been developed rapidly and it has been applied in the studies of steel integrated structures, ferro-elastic ceramics, human retina, semiconductors, composites, etc. In acoustic microscopy, V(z) curves have been used to investigate the visco-elastic parameters of thin sliced samples of composites, animal tissue, etc., while in this work it is applied in characterizing the geometry of periodically corrugated structures. The measurements of the geometry of periodic structures obtained using acoustic microscopy are compared with those obtained using optical microscopy, and the reliability of this acoustic technique is also examined. PMID- 27259117 TI - A comprehensive numerical analysis of background phase correction with V-SHARP. AB - Sophisticated harmonic artifact reduction for phase data (SHARP) is a method to remove background field contributions in MRI phase images, which is an essential processing step for quantitative susceptibility mapping (QSM). To perform SHARP, a spherical kernel radius and a regularization parameter need to be defined. In this study, we carried out an extensive analysis of the effect of these two parameters on the corrected phase images and on the reconstructed susceptibility maps. As a result of the dependence of the parameters on acquisition and processing characteristics, we propose a new SHARP scheme with generalized parameters. The new SHARP scheme uses a high-pass filtering approach to define the regularization parameter. We employed the variable-kernel SHARP (V-SHARP) approach, using different maximum radii (Rm ) between 1 and 15 mm and varying regularization parameters (f) in a numerical brain model. The local root-mean square error (RMSE) between the ground-truth, background-corrected field map and the results from SHARP decreased towards the center of the brain. RMSE of susceptibility maps calculated with a spatial domain algorithm was smallest for Rm between 6 and 10 mm and f between 0 and 0.01 mm-1 , and for maps calculated with a Fourier domain algorithm for Rm between 10 and 15 mm and f between 0 and 0.0091 mm-1 . We demonstrated and confirmed the new parameter scheme in vivo. The novel regularization scheme allows the use of the same regularization parameter irrespective of other imaging parameters, such as image resolution. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27259119 TI - The effects of fracture permeability on acoustic wave propagation in the porous media: A microscopic perspective. AB - An illustrative theory is developed to analyze the acoustic wave propagation characteristics in the porous media with anisotropic permeability. We focus here on the role of fracture permeability in the unconsolidated porous media, looking in particular at the compressional P-wave phase velocity and attenuation. Two fluid pressure equilibration characteristic time factors are defined, which are corresponding to crack-pore system and crack-crack system, respectively. The theoretical results show that the dispersion and attenuation characteristics of acoustic wave are affected by porous matrix and fracture permeability simultaneously. Due to the fluid exchange that takes place between fractures and pores dominantly, the influence of the fracture connectivity on the wave propagation is very weak when the permeability of background medium is relatively high. However, correlation between wave propagation and fracture permeability is significant when the matrix permeability at a low level. A second attenuation peak occurs for the fluid flow within fractures in high-frequency region for more and more higher fracture permeability. The exact analytical solutions that are compared to numerical forward modeling of wave propagation in fractured media allow us to verify the correctness of the new model. If there exists another approach for obtaining the connectivity information of background media, we can use this model to analyze qualitatively the permeability of fractures or afford an indicator of in-situ permeability changes in a oil reservoir, for example, fracturing operations. PMID- 27259121 TI - From the Editor. PMID- 27259122 TI - Guest Editorial. PMID- 27259123 TI - Nurses and Psychologists Advancing the Patient-Centered Medical Home Model. AB - As America experiences the largest health care revolution of the past 50 years, clinicians and administrators are refocusing their attention on the goals of the Quadruple Aim. Motivation and capabilities among stakeholders vary as practical tools and an adequate workforce remain elusive. At the same time, the patient centered medical home (PCMH) model is spreading rapidly but demonstrating variable results. Positive PCMH outcomes seem to reflect high-quality teamwork. A primary care physician shortage is looming, and increasing numbers of health professionals are being pushed into the PCMH, mandated to provide "integrated" care. Even now, the majority of our Graduate Medical Education programs do not train clinicians in team-based workflow models and interaction skills. Consequently, PCMH teams will only optimize and realize the model's true potential if they learn to coordinate, communicate, and collaborate effectively. This means all PCMH staff members achieve solid teamwork skills and work at the top of their license. The authors discuss resources for improving coordination, communication, and collaboration among members of PCMH teams, and strategies for including other professionals. PMID- 27259124 TI - Interview. PMID- 27259125 TI - Experience of Psychiatric Mental Health Nurse Practitioners in Public Mental Health. AB - Expansion of health insurance coverage under the Accountable Care Act has meant that millions of people are now insured for mental health treatment, but with no significant increase in the mental health workforce. Services of psychiatric mental health nurse practitioners (PMHNPs) may be best utilized to improve access to and quality of public mental health services if the financial, political, scope of practice, and treatment model barriers that limit their ability or willingness to practice in these settings are better understood. This article reports qualitative results from a study that assessed barriers and best practices in the use of PMHNPs in county mental health services in California. Results indicate that PMHNPs are valued for their "whole person" perspective, collaborative approach, and interpersonal communication skills, but that significant knowledge gaps, regulatory constraints, and bureaucratic barriers in public mental health systems inhibit PMHNPs from practicing at the top of their scope. PMID- 27259126 TI - American Psychiatric Nurses Association-Transitions in Practice Certificate Program: Bridging the Knowledge Gap in Caring for Psychiatric Patients Within the General Nursing Workforce. AB - The purpose of this article is to publicize an important new Web-based educational program. Recognizing the growing gap in psychiatric-mental health knowledge and the need to better prepare new graduates and nurses transitioning from other service lines into psychiatric inpatient nursing settings, the American Psychiatric Nurses Association developed a 15-hour, modularized curriculum to provide foundational psychiatric-mental health knowledge. This modularized curriculum, called American Psychiatric Nurses Association Transitions in Practice (ATP) focuses on the knowledge and skills to insure the success of nurses new to psychiatric-mental health nursing settings and to improve the overall care for persons with mental health and substance use disorders. The ATP program is also proving to be useful content for nurses in emergency departments, hospitals, and other health settings to improve their care of patients with psychiatric and mental health needs. A summary of the program modules and a toolkit with suggested measures for nurses, patients, and agency outcomes is described. Feedback from participants completing the ATP program within the first 6 months is overwhelmingly positive and holds promise for widespread application across a variety of health care settings. PMID- 27259127 TI - Empowering Staff Nurses With Essential Skills: Training Strategies for Success. AB - Nurse leaders in the mental health field are challenged to ensure the mental health environment is safe and therapeutic. They must also continually evaluate whether nurses are effectively engaging therapeutically with patients in their care. Undergraduate nursing students and practicing nurses usually receive little or no training in facilitating nurse-led groups. Nurses who are trained and capable of facilitating groups may enhance therapeutic relationships and engage patients to improve treatment outcomes. Training staff and disseminating educational materials in an efficient manner are often challenges for nurse leaders. The Veterans Health Administration (VHA) Office of Nursing Services (ONS) Mental Health Field Advisory Committee (MH-FAC) developed a nursing guide for conducting psychoeducation groups. This was followed up with a complementary live virtual training with "on-demand" features that included discussion and demonstration of nurse-led group implementation strategies. Both products were disseminated to nurse leaders throughout the VHA ONS Web site. Responses to both the guide and video were overwhelmingly positive. This article discusses the importance of nurse-led psychoeducational groups and describes a project implemented by the ONS MH-FAC, which helped provide an essential training to more than 1100 RNs within the Veterans Affairs Health System nationally. PMID- 27259128 TI - Improving Management of Behavioral and Psychological Symptoms of Dementia in Acute Care: Evidence and Lessons Learned From Across the Care Spectrum. AB - As the prevalence of Alzheimer disease and related dementias increases, dementia related behavioral symptoms present growing threats to care quality and safety of older adults across care settings. Behavioral and psychological symptoms of dementia (BPSD) such as agitation, aggression, and resistance to care occur in nearly all individuals over the course of their illness. In inpatient care settings, if not appropriately treated, BPSD can result in care complications, increased length of stay, dissatisfaction with care, and caregiver stress and injury. Although evidence-based, nonpharmacological approaches to treating BPSD exist, their implementation into acute care has been thwarted by limited nursing staff expertise in behavioral health, and a lack of consistent approaches to integrate behavioral health expertise into medically focused inpatient care settings. This article describes the core components of one evidence-based approach to integrating behavioral health expertise into dementia care. This approach, called STAR-VA, was implemented in Veterans' Health Administration community living centers (nursing homes). It has demonstrated effectiveness in reducing the severity and frequency of BPSD, while improving staff knowledge and skills in caring for people with dementia. The potential for adapting this approach in acute care settings is discussed, along with key lessons learned regarding opportunities for nursing leadership to ensure consistent implementation and sustainability. PMID- 27259129 TI - The Pathway to Excellence Experience: One Psychiatric Hospital's Journey. AB - Psychiatric nurse executives and managers face an ongoing challenge to create positive professional work environments that support the recruitment and retention of the best nurses. The Pathway to Excellence program is an organizational credentialing program that designates a hospital as a workplace of choice for nursing. This article describes one psychiatric hospital's journey to become and maintain a Pathway to Excellence designation in the midst of transition. Challenges faced and novel approaches used, along the journey, are shared. The use of Appreciative Inquiry techniques has led to positive changes and heightened energy among nurses. Our experiences suggest that effective shared governance is central to a hospital's Pathway to Excellence success. We attribute the steady increase in the retention rate of nurses, in large part, to the Pathway to Excellence program. PMID- 27259130 TI - Interdisciplinary Shared Governance in Ambulatory Care: One Health System's Journey. AB - The implementation of shared governance structures in acute care has illustrated the positive relationship between shared decision making and nurse empowerment and positive nurse and patient outcomes. Little is known, however, about interdisciplinary shared governance, and even less is known about shared governance in ambulatory care. This article details one health system's experience with the implementation of an interdisciplinary shared governance structure in ambulatory care over a 4-year period. The authors report lessons learned, positive health system outcomes that resulted including improved communication, better preparedness for accreditation visits, improved assessment of fall risk, and a streamlined documentation system. Also discussed are mechanisms to enhance sustainability of the structure and discussion of future opportunities and challenges. PMID- 27259131 TI - A Holistic Approach to Improve Nursing Retention During the First Year of Employment. AB - The national nursing shortage, coupled with our country's financial challenges, provides a platform for creative nursing retention practices by health care organizations. It was from that platform that this research study was undertaken to determine if nurses who receive a high level of personal interest, education, and support through self-care workshops and one-on-one communication would continue their employment at the organization. The research question was "Will providing holistic self-care workshops during the first year of employment impact the nursing retention rates?" A total of 89 newly hired nurses were enrolled in the study, in which they participated in a 90-minute interactive workshop held weekly for 4 consecutive weeks. In the workshops, the nurses were guided to an understanding of the importance of self-care activities. The responses of the nurses who participated were positive. As a result of this study, the self-care workshops have continued with modification in length and the time when they were provided. PMID- 27259132 TI - The Continued Need to Balance Preparation and Scope of Practice to Meet Behavioral Health Needs. PMID- 27259133 TI - Addressing the Elephant in the Room: Nurse Manager Recognition of and Response to Nurse-to-Nurse Bullying. AB - Health care bullying is a pervasive, underestimated, and underreported problem that results in poor outcomes for staff, patients, and health care organizations. The most common form of health care bullying occurs between nurses. Nurse managers hold an important role in the prevention and elimination of frontline nurse-to-nurse bullying. An anonymous Web-based survey was conducted to uncover what behaviors nurse managers perceive as bullying and how they respond to bullying acts. Respondents who had witnessed or been victimized by bullying were more apt to identify bullying and those who had been victimized or supervised nurses for more than 20 years were more prone to act upon bullying behaviors. There was only a moderate correlation between the identification of and response to bullying behaviors. Finally, overt bullying elicited a stronger response for intervention than covert bullying. Although nurse managers are well positioned to prevent and eliminate nurse-to-nurse bullying, they may not recognize it and often lack the skills and support necessary to address it. Decreases in nurse-to nurse bullying reduce health care costs, improve nurse and patient satisfaction, and enhance patient outcomes. Therefore, nurse managers at all levels need education and support to ensure proper identification of bullying and, furthermore, to prevent and eliminate the behaviors. PMID- 27259134 TI - Buccal Bone Thickness Overlying Maxillary Anterior Teeth: A Clinical and Radiographic Prospective Human Study. AB - OBJECTIVES: The aim of this work was to measure the facial bone thickness overlying maxillary anterior teeth according to the periodontal biotype, the tooth position, and the bucco-palatal inclination of the tooth. MATERIALS AND METHODS: CBCTs of 47 patients were included. The periodontal biotype and the bucco-palatal inclination were examined for all maxillary anterior teeth as well as the sagittal tooth position according to the classification of Kan et al. Buccal bone thickness was measured at 4, 6, 8, and 10 mm apical to the cement enamel junction (CEJ). RESULTS: At 4 mm from the CEJ, mean buccal bone thickness was 1.0 mm for all teeth and it decreased gradually and significantly in apical direction (6, 8, and 10 mm). A thin biotype was associated with a labial plate thickness half that of a thick biotype at all 4 distances from the CEJ. Class IV of Kan et al classification presented the thinnest facial bone (0.32-0.54 mm), whereas Class III demonstrated the thickest one (1.26-2.09 mm) at all distances from the CEJ. At 10 mm from the CEJ, the facial bone thickness increased with the vestibulo-palatal inclination of the tooth. CONCLUSION: A thin facial bone wall overlies almost all maxillary anterior teeth. PMID- 27259135 TI - Relationship between adipic acid concentration and the core symptoms of autism spectrum disorders. AB - Dicarboxylic acids are an important source of information about metabolism and potential physiopathological alterations in children with autism spectrum disorders (ASDs). We measured the concentration between dicarboxylic adipic and suberic acids in children with an ASD and typically-developing (TD) children and analyzed any relationships between the severity of the core symptoms of ASDs and other clinical features (drugs, supplements, drugs, or diet). The core symptoms of autism were evaluated using the DSM-IV criteria, and adipic acid and suberic acid were measured in urine samples. Overall, no increase in the concentration of adipic acid in children with ASDs compared to TD children, however when considering vitamin B supplementation in ASD there were significantly increased level of urinary adipic acid in children with an ASD not taking vitamin B supplementation compared to supplemented children or to TD children. No significant difference were observed in suberic acid. Interestingly, the increase in adipic acid concentration was significantly and indirectly correlated with the severity of the deficit in socialization and communication skills in children with an ASD. Therefore, therapeutic treatments aimed at decreasing adipic acid concentration might not be beneficial for treating the core symptoms of ASDs. PMID- 27259136 TI - Reliability and validity of a semi-structured DSM-based diagnostic interview module for the assessment of Attention Deficit Hyperactivity Disorder in adult psychiatric outpatients. AB - Despite growing recognition that the symptoms and functional impairments of Attention Deficit/Hyperactivity Disorder (ADHD) persist into adulthood, only a few psychometrically sound diagnostic measures have been developed for the assessment of ADHD in adults, and none have been validated for use in a broad treatment-seeking psychiatric sample. The current study presents the reliability and validity of a semi-structured DSM-based diagnostic interview module for ADHD, which was administered to 1194 adults presenting to an outpatient psychiatric practice. The module showed excellent internal consistency and interrater reliability, good convergent and discriminant validity (as indexed by relatively high correlations with self-report measures of ADHD and ADHD-related constructs and little or no correlation with other, non-ADHD symptom domains), and good construct validity (as indexed by significantly higher rates of psychosocial impairment and self-reported family history of ADHD in individuals who meet criteria for an ADHD diagnosis). This instrument is thus a reliable and valid diagnostic tool for the detection of ADHD in adults presenting for psychiatric evaluation and treatment. PMID- 27259138 TI - Meet the Editors. AB - Significant progress has been made to improve and diversify the genome-editing toolbox. PMID- 27259137 TI - The Violent Content in Attenuated Psychotic Symptoms. AB - The relationship between psychosis and violence has typically focused on factors likely to predict who will commit violent acts. One unexplored area is violence in the content of subthreshold positive symptoms. The current aim was to conduct an exploratory analysis of violent content in the attenuated psychotic symptoms (APS) of those at clinical high risk of psychosis (CHR) who met criteria for attenuated psychotic symptom syndrome (APSS). The APS of 442 CHR individuals, determined by the Structured Interview for Prodromal Syndromes, were described in comprehensive vignettes. The content of these symptoms were coded using the Content of Attenuated Positive Symptoms Codebook. Other measures included clinical symptoms, functioning, beliefs and trauma. Individuals with violent content had significantly higher APS, greater negative beliefs about the self and others, and increased bullying. The same findings and higher ratings on anxiety symptoms were present when participants with self-directed violence were compared to participants with no violent content. Individuals reporting violent content differ in their clinical presentation compared to those who do not experience violent content. Adverse life events, like bullying, may impact the presence of violent content in APS symptoms. Future studies should explore violent content in relation to actual behavior. PMID- 27259139 TI - Learning from the Uncontrollable. PMID- 27259140 TI - Developing Effective Treatments for Psychiatric Diseases. PMID- 27259141 TI - Do Flies Count Sheep or NMDA Receptors to Go to Sleep? AB - The drive to sleep increases the longer that we stay awake, but this process is poorly understood at the cellular level. Now, Liu et al. show that the plasticity of a small group of neurons in the Drosophila central brain is a key component of the sleep homeostat. PMID- 27259142 TI - Dangerous Entrapment for NRF2. AB - Progerin, a mutated lamin A, causes the severe premature-aging syndrome Hutchinson-Gilford progeria (HGPS). Kubben et al. present a driving mechanism for HGPS involving trapping of NRF2 at the nuclear periphery by progerin. This local restriction results in impaired NRF2 signaling and chronic oxidative stress. PMID- 27259143 TI - A Pro-metastatic tRNA Pathway. AB - tRNAs are best known as basic modules for global regulation of protein synthesis. Goodarzi et al. now show that two tRNAs upregulated in metastatic breast cancer cells enhance stability and translation of transcripts enriched with these codons, leading to specific increase in production of pro-metastatic proteins. PMID- 27259144 TI - A TOGgle for Tension at Kinetochores. AB - Differential stability of kinetochore-microtubule attachments at low versus high tension is critical for accurate chromosome segregation. Miller et al. find that a TOG domain microtubule-binding protein imparts intrinsic tension selectivity to kinetochore-microtubule attachments. PMID- 27259145 TI - Leveraging Rules of Nonsense-Mediated mRNA Decay for Genome Engineering and Personalized Medicine. AB - Nonsense-mediated mRNA decay (NMD) is a eukaryotic mRNA quality control and regulatory process that plays direct roles in human health and disease. In this Minireview, we discuss how understanding the molecular events that trigger NMD can facilitate strategic targeting of genes via CRISPR/Cas9 technologies and also inform disease diagnostics and treatments. PMID- 27259146 TI - Cooperative Microbial Tolerance Behaviors in Host-Microbiota Mutualism. AB - Animal defense strategies against microbes are most often thought of as a function of the immune system, the primary function of which is to sense and kill microbes through the execution of resistance mechanisms. However, this antagonistic view creates complications for our understanding of beneficial host microbe interactions. Pathogenic microbes are described as employing a few common behaviors that promote their fitness at the expense of host health and fitness. Here, a complementary framework is proposed to suggest that, in addition to pathogens, beneficial microbes have evolved behaviors to manipulate host processes in order to promote their own fitness and do so through the promotion of host health and fitness. In this Perspective, I explore the idea that patterns or behaviors traditionally ascribed to pathogenic microbes are also employed by beneficial microbes to promote host tolerance defense strategies. Such strategies would promote host health without having a negative impact on microbial fitness and would thereby yield cooperative evolutionary dynamics that are likely required to drive mutualistic co-evolution of hosts and microbes. PMID- 27259147 TI - From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. AB - A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease. PMID- 27259148 TI - Repression of the Antioxidant NRF2 Pathway in Premature Aging. AB - Hutchinson-Gilford progeria syndrome (HGPS) is a rare, invariably fatal premature aging disorder. The disease is caused by constitutive production of progerin, a mutant form of the nuclear architectural protein lamin A, leading, through unknown mechanisms, to diverse morphological, epigenetic, and genomic damage and to mesenchymal stem cell (MSC) attrition in vivo. Using a high-throughput siRNA screen, we identify the NRF2 antioxidant pathway as a driver mechanism in HGPS. Progerin sequesters NRF2 and thereby causes its subnuclear mislocalization, resulting in impaired NRF2 transcriptional activity and consequently increased chronic oxidative stress. Suppressed NRF2 activity or increased oxidative stress is sufficient to recapitulate HGPS aging defects, whereas reactivation of NRF2 activity in HGPS patient cells reverses progerin-associated nuclear aging defects and restores in vivo viability of MSCs in an animal model. These findings identify repression of the NRF2-mediated antioxidative response as a key contributor to the premature aging phenotype. PMID- 27259149 TI - Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development. AB - How the chromatin regulatory landscape in the inner cell mass cells is established from differentially packaged sperm and egg genomes during preimplantation development is unknown. Here, we develop a low-input DNase I sequencing (liDNase-seq) method that allows us to generate maps of DNase I hypersensitive site (DHS) of mouse preimplantation embryos from 1-cell to morula stage. The DHS landscape is progressively established with a drastic increase at the 8-cell stage. Paternal chromatin accessibility is quickly reprogrammed after fertilization to the level similar to maternal chromatin, while imprinted genes exhibit allelic accessibility bias. We demonstrate that transcription factor Nfya contributes to zygotic genome activation and DHS formation at the 2-cell stage and that Oct4 contributes to the DHSs gained at the 8-cell stage. Our study reveals the dynamic chromatin regulatory landscape during early development and identifies key transcription factors important for DHS establishment in mammalian embryos. PMID- 27259150 TI - Modulated Expression of Specific tRNAs Drives Gene Expression and Cancer Progression. AB - Transfer RNAs (tRNAs) are primarily viewed as static contributors to gene expression. By developing a high-throughput tRNA profiling method, we find that specific tRNAs are upregulated in human breast cancer cells as they gain metastatic activity. Through loss-of-function, gain-of-function, and clinical association studies, we implicate tRNAGluUUC and tRNAArgCCG as promoters of breast cancer metastasis. Upregulation of these tRNAs enhances stability and ribosome occupancy of transcripts enriched for their cognate codons. Specifically, tRNAGluUUC promotes metastatic progression by directly enhancing EXOSC2 expression and enhancing GRIPAP1-constituting an "inducible" pathway driven by a tRNA. The cellular proteomic shift toward a pro-metastatic state mirrors global tRNA shifts, allowing for cell-state and cell-type transgene expression optimization through codon content quantification. TRNA modulation represents a mechanism by which cells achieve altered expression of specific transcripts and proteins. TRNAs are thus dynamic regulators of gene expression and the tRNA codon landscape can causally and specifically impact disease progression. PMID- 27259152 TI - Relative Rates of Surface and Volume Synthesis Set Bacterial Cell Size. AB - Many studies have focused on the mechanisms underlying length and width determination in rod-shaped bacteria. Here, we focus instead on cell surface area to volume ratio (SA/V) and demonstrate that SA/V homeostasis underlies size determination. We propose a model whereby the instantaneous rates of surface and volume synthesis both scale with volume. This model predicts that these relative rates dictate SA/V and that cells approach a new steady-state SA/V exponentially, with a decay constant equal to the volume growth rate. To test this, we exposed diverse bacterial species to sublethal concentrations of a cell wall biosynthesis inhibitor and observed dose-dependent decreases in SA/V. Furthermore, this decrease was exponential and had the expected decay constant. The model also quantitatively describes SA/V alterations induced by other chemical, nutritional, and genetic perturbations. We additionally present evidence for a surface material accumulation threshold underlying division, sensitizing cell length to changes in SA/V requirements. PMID- 27259151 TI - Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. AB - Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3 anaphase-promoting complex/cyclosome (APC/C) and its two partner E2s, UBE2C (aka UBCH10) and UBE2S, adopt specialized catalytic architectures for these two distinct forms of polyubiquitination. The APC/C RING constrains UBE2C proximal to a substrate and simultaneously binds a substrate-linked UB to drive processive multiubiquitination. Alternatively, during UB chain elongation, the RING does not bind UBE2S but rather lures an evolving substrate-linked UB to UBE2S positioned through a cullin interaction to generate a Lys11-linked chain. Our findings define mechanisms of APC/C regulation, and establish principles by which specialized E3-E2-substrate-UB architectures control different forms of polyubiquitination. PMID- 27259153 TI - Direct Identification of Hundreds of Expression-Modulating Variants using a Multiplexed Reporter Assay. AB - Although studies have identified hundreds of loci associated with human traits and diseases, pinpointing causal alleles remains difficult, particularly for non coding variants. To address this challenge, we adapted the massively parallel reporter assay (MPRA) to identify variants that directly modulate gene expression. We applied it to 32,373 variants from 3,642 cis-expression quantitative trait loci and control regions. Detection by MPRA was strongly correlated with measures of regulatory function. We demonstrate MPRA's capabilities for pinpointing causal alleles, using it to identify 842 variants showing differential expression between alleles, including 53 well-annotated variants associated with diseases and traits. We investigated one in detail, a risk allele for ankylosing spondylitis, and provide direct evidence of a non coding variant that alters expression of the prostaglandin EP4 receptor. These results create a resource of concrete leads and illustrate the promise of this approach for comprehensively interrogating how non-coding polymorphism shapes human biology. PMID- 27259155 TI - p53-Dependent Nestin Regulation Links Tumor Suppression to Cellular Plasticity in Liver Cancer. PMID- 27259154 TI - Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits. AB - Genome-wide association studies (GWAS) have successfully identified thousands of associations between common genetic variants and human disease phenotypes, but the majority of these variants are non-coding, often requiring genetic fine mapping, epigenomic profiling, and individual reporter assays to delineate potential causal variants. We employ a massively parallel reporter assay (MPRA) to simultaneously screen 2,756 variants in strong linkage disequilibrium with 75 sentinel variants associated with red blood cell traits. We show that this assay identifies elements with endogenous erythroid regulatory activity. Across 23 sentinel variants, we conservatively identified 32 MPRA functional variants (MFVs). We used targeted genome editing to demonstrate endogenous enhancer activity across 3 MFVs that predominantly affect the transcription of SMIM1, RBM38, and CD164. Functional follow-up of RBM38 delineates a key role for this gene in the alternative splicing program occurring during terminal erythropoiesis. Finally, we provide evidence for how common GWAS-nominated variants can disrupt cell-type-specific transcriptional regulatory pathways. PMID- 27259156 TI - Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. PMID- 27259157 TI - Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans. PMID- 27259158 TI - Polypyrrole-Coated Zinc Ferrite Hollow Spheres with Improved Cycling Stability for Lithium-Ion Batteries. AB - Here, ZnFe2 O4 double-shell hollow microspheres are designed to accommodate the large volume expansion during lithiation. A facile and efficient vapor-phase polymerization method has been developed to coat the ZnFe2 O4 hollow spheres with polypyrrole (PPY). The thin PPY coating improves not only the electronic conductivity but also the structural integrity, and thus the cycling stability of the ZnFe2 O4 hollow spheres. Our work sheds light on how to enhance the electrochemical performance of transition metal oxide-based anode materials by designing delicate nanostructures. PMID- 27259159 TI - Structure - membrane activity relationship in a family of peptide-based gemini amphiphiles: An insight from experimental and theoretical model systems. AB - A study of the interaction between five gemini amphiphilic valine-based pseudopeptides (GAPs) differing by the length of the central aliphatic spacer linking two amino acid subunits, and a model bacterial membrane lipid, 1,2 dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG), is here presented. Pure DMPG, pure GAPs and mixed GAPs/DMPG monolayers were formed at the air-water interface using Langmuir technique. The properties of the Langmuir films were investigated using surface pressure measurements, polarization modulation infrared reflection-absorption spectroscopy, and Brewster angle microscopy. The atomic level information concerning the orientation of molecules in the monolayer and hydration of the polar headgroups was obtained from molecular dynamics simulations. It was demonstrated that the length of the central spacer in the GAPs structure is important for the properties of the mixed films; the disorganization of the membrane increases with the length of the spacer. The latter point is important for developing possible antimicrobial agents based on GAPs. PMID- 27259161 TI - Countering drug resistance, infectious diseases, and sepsis using metal and metal oxides nanoparticles: Current status. AB - One fourth of the global mortalities is still caused by microbial infections largely due to the development of resistance against conventional antibiotics among pathogens, the resurgence of old infectious diseases and the emergence of hundreds of new infectious diseases. The lack of funds and resources for the discovery of new antibiotics necessitates the search for economic and effective alternative antimicrobial agents. Metal and metal oxide nanoparticles including silver and zinc oxide exhibit remarkable antimicrobial activities against pathogens and hence are one of the most propitious alternative antimicrobial agents. These engineered nanomaterials are approved by regulatory agencies such as USFDA and Korea's FITI, for use as antimicrobial agents, supplementary antimicrobials, food packaging, skin care products, oral hygiene, and for fortifying devices prone to microbial infections. Nevertheless, detailed studies, on molecular and biochemical mechanisms underlying their antimicrobial activity are missing. To take the full advantage of this emerging technology selective antimicrobial activity of these nanoparticles against pathogens should be studied. Optimization of these nanomaterials through functionalization to increase their efficacy and biocompatibility is also required. Urgent in vivo studies on the toxicity of nanomaterials at realistic doses are also needed before their clinical translation. PMID- 27259160 TI - Regulation of biphasic drug release behavior by graphene oxide in polyvinyl pyrrolidone/poly(epsilon-caprolactone) core/sheath nanofiber mats. AB - One of the key issues for drug delivery systems is to develop a drug carrier with a time-programmed, biphasic release behavior. Using vancomycin hydrochloride (VAN) as a model drug, polyvinyl pyrrolidone (PVP) blended with graphene oxide (GO) sheets as the core matrix, and poly(epsilon-caprolactone) (PCL) as the sheath polymer, core/sheath PVP/PCL nanofiber mats were fabricated via a coaxial electrospinning process. We hypothesized that the addition of GO sheets would lead to their molecular interactions with VAN molecules, thereby adjusting the VAN release behavior. Field emission scanning electron microscopy and transmission electron microscopy of the fiber mats revealed their nanofibrous structure and clear core/sheath boundary. Raman analysis demonstrated the presence of GO sheets in the PVP/PCL nanofiber mats. Fourier transform infrared spectroscopy indicated the formation of hydrogen bonds between GO sheets and VAN molecules. In vitro studies showed that the PVP/PCL nanofiber mats were biocompatible, despite the addition of GO sheets, and exhibited typical biphasic drug release profiles, which were tailored by adjusting the content of GO sheets. Furthermore, an antimicrobial test showed different antimicrobial activities of the medicated nanofiber mats, depending on the GO content. Collectively, the results of the present study provide a simple approach to obtaining time programmed drug release profiles. PMID- 27259162 TI - Overview of regulation of dietary supplements in the USA and issues of adulteration with phenethylamines (PEAs). AB - The multi-billion dollar dietary supplement industry is global in reach. The industry has been criticized for problems related to poor quality control, safety, misbranding, and adulteration. In this review, we describe how the US Food and Drug Administration (FDA) regulates dietary supplements within the framework of the Federal Food, Drug, and Cosmetic Act (FD&C Act). The Dietary Supplement Health and Education Act of 1994 (DSHEA), which amended the FD&C Act, gave the FDA the authority to promulgate Good Manufacturing Practices for dietary supplements and required that manufacturers provide the FDA information supporting a conclusion that the ingredients are reasonably expected to be safe if the dietary ingredients were not marketed in the USA before 15 October 1994. Recent amendments to the FD&C Act require that serious dietary-supplement-related adverse events be reported to the FDA and provide the agency with mandatory recall authority. We discuss the presence of naturally occurring (e.g. Ephedra, Citrus aurantium, Acacia) and synthetic (e.g. beta-methylphenethylamines, methylsynephrine, alpha-ethyl-phenethylamine) biologically active phenethylamines (PEAs) in dietary supplements and of PEA drugs (e.g. clenbuterol, fenfluramine, sibutramine, lorcaserin) in weight-loss products. Regulatory actions against manufacturers of products labelled as dietary supplements that contain the aliphatic amines 1,3-dimethylamine and 1,3-dimethylbutylamine, and PEAs such as beta-methylphenethylamine, aegeline, and Dendrobium illustrate the FDA's use of its authority under the FD&C Act to promote dietary supplement safety. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27259163 TI - Error in Reported Data for Dense Breast Notifications. PMID- 27259164 TI - Iodide Residues in Milk Vary between Iodine-Based Teat Disinfectants. AB - Majority of iodine found in dairy milk comes from the diet and teat disinfection products used during milking process. The objective of this study was to evaluate the effects of 4 iodine-based teat dips on milk iodide concentrations varying in iodine level (0.25% vs. 0.5%, w/w), normal low viscosity dip versus barrier dip, and application method (dip vs. spray) to ensure safe iodine levels in dairy milk when these products are used. The iodine exposure study was performed during a 2 wk period. The trial farm was purged of all iodine-based disinfection products for 21 d during a prestudy "washout period," which resulted in baseline milk iodide range of 145 to 182 ppb. During the experiment, iodine-based teat dips were used as post-milking teat disinfectants and compared to a non-iodine control disinfectant. Milk iodide residue levels for each treatment was evaluated from composited group samples. Introduction of different iodine-based teat disinfectants increased iodide residue content in milk relative to the control by between 8 and 29 MUg/L when averaged across the full trial period. However, residues levels for any treatment remained well below the consumable limit of 500 MUg/L. The 0.5% iodine disinfectant increased milk iodide levels by 20 MUg/L more compared to the 0.25% iodine. Compared to dip-cup application, spray application significantly increased milk iodide residue by 21 MUg/L and utilized approximately 23% more teat dip. This carefully controlled study demonstrated an increase in milk iodide concentrations from iodine disinfectants, but increases were small and within acceptable limits. PMID- 27259165 TI - Alterations in regional shape on ipsilateral and contralateral cortex contrast in children with unilateral cerebral palsy and are predictive of multiple outcomes. AB - Congenital brain lesions result in a wide range of cerebral tissue alterations observed in children with cerebral palsy (CP) that are associated with a range of functional impairments. The relationship between injury severity and functional outcomes, however, remains poorly understood. This research investigates the differences in cortical shape between children with congenital brain lesions and typically developing children (TDC) and investigates the correlations between cortical shape and functional outcome in a large cohort of patients diagnosed with unilateral CP. Using 139 structural magnetic resonance images, including 95 patients with clinically diagnosed CP and 44 TDC, cortical segmentations were obtained using a modified expectation maximization algorithm. Three shape characteristics (cortical thickness, curvature, and sulcal depth) were computed within a number of cortical regions. Significant differences in these shape measures compared to the TDC were observed on both the injured hemisphere of children with CP (P < 0.004), as well as on the apparently uninjured hemisphere, illustrating potential compensatory mechanisms in these children. Furthermore, these shape measures were significantly correlated with several functional outcomes, including motor, cognition, vision, and communication (P < 0.012), with three out of these four models performing well on test set validation. This study highlights that cortical neuroplastic effects may be quantified using MR imaging, allowing morphological changes to be studied longitudinally, including any influence of treatment. Ultimately, such approaches could be used for the long term prediction of outcomes and the tailoring of treatment to individuals. Hum Brain Mapp 37:3588-3603, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27259166 TI - Resting multilayer 2D speckle-tracking transthoracic echocardiography for the detection of clinically stable myocardial ischemic segments confirmed by invasive fractional flow reserve. Part 1: Vessel-by-vessel analysis. AB - PURPOSE: To detect stable ischemic left ventricular (LV)-segments confirmed via invasive fractional flow reserve (FFR) by quantitative longitudinal-strain (LS) determined using resting multilayer TTE. METHODS: A retrospective analysis of 39 stable patients (32 males; 65.8+/-11.9years) with 46 coronary arteries with >=50% stenosis confirmed by invasive coronary angiography who underwent invasive FFR measurement and TTE (Vivid E9, GE). On TTE, regional LS (absolute values) were calculated in whole, endocardial, and epicardial layers perfused by stenotic coronary arteries. RESULTS: Of the 46 vessels, FFR values of <0.75, >=0.75, <=0.80 and >0.80 were observed in 17, 29, 27 and 19 vessels, respectively. In a vessel-by-vessel analysis, the whole-layer and endocardial LS were significantly smaller in LV-segments perfused by vessels with an FFR<0.75 than in those with an FFR>=0.75, but epicardial LS was not. In ROC curves, the best cutoff values of whole-layer, endocardial and epicardial LS were, respectively, 14.0% (sensitivity, 94%; specificity 38%; area under the curve, 0.685), 10.0% (47%; 86%; 0.664) and 14.0% (100%; 24%; 0.640) to detect LV-segments with an FFR<0.75; and 14.0% (82%; 37%; 0.561), 10.0% (33%; 84%; 0.573), and 14.0% (89%; 21%; 0.538) to detect LV-segments with an FFR<=0.80. CONCLUSION: For stable subjects with coronary arteries with >=50% stenosis, the regional whole-layer and endocardial LS were significantly smaller in LV-segments perfused by vessels with an FFR<0.75 than in those with an FFR>=0.75, but epicardial LS was not; and that the whole layer and endocardial LS had a modest diagnostic efficiency in identifying LV segments perfused by vessels with an FFR<0.75. PMID- 27259167 TI - Molecular and Clinical Findings in Patients With Knobloch Syndrome. AB - IMPORTANCE: Knobloch syndrome is a rare, recessively inherited disorder classically characterized by high myopia, retinal detachment, and occipital encephalocele, but it is now known to have an increasingly variable phenotype. There is a lack of reported electrophysiologic data, and some key clinical features have yet to be described. OBJECTIVE: To expand on current clinical, electrophysiologic, and molecular genetic findings in Knobloch syndrome. DESIGN, SETTING, AND PARTICIPANTS: Twelve patients from 7 families underwent full ophthalmic examination and retinal imaging. Further investigations included electroretinography and neuroradiologic imaging. Bidirectional Sanger sequencing of COL18A1 was performed with segregation on available relatives. The study was conducted from July 4, 2013, to October 5, 2015. Data analysis was performed from May 20, 2014, to November 3, 2015. MAIN OUTCOMES AND MEASURES: Results of ophthalmic and neuroradiologic assessment and sequence analysis of COL18A1. RESULTS: Of the 12 patients (6 males; mean age at last review, 16 years [range, 2 38 years]), all had high myopia in at least 1 eye and severely reduced vision. A sibling pair had unilateral high myopia in their right eyes and near emmetropia in their left eyes from infancy. Anterior segment abnormalities included absent iris crypts, iris transillumination, lens subluxation, and cataract. Two patients with iris transillumination had glaucoma. Fundus characteristics included abnormal collapsed vitreous, macular atrophy, and a tesselated fundus. Five patients had previous retinal detachment. Electroretinography revealed a cone-rod pattern of dysfunction in 8 patients, was severely reduced or undetectable in 2 patients, and demonstrated cone-rod dysfunction in 1 eye with undetectable responses in the other eye in 2 patients. Radiologic imaging demonstrated occipital encephalocele or meningocele in 3 patients, occipital skull defects in 4 patients, minor occipital changes in 2 patients, and no abnormalities in 2 patients. Cutaneous scalp changes were present in 5 patients. Systemic associations were identified in 8 patients, including learning difficulties, epilepsy, and congenital renal abnormalities. Biallelic mutations including 2 likely novel mutations in COL18A1, were identified in 6 families that were consistent with autosomal recessive inheritance with a single mutation identified in a family with 2 affected children. CONCLUSIONS AND RELEVANCE: This report describes new features in patients with Knobloch syndrome, including pigment dispersion syndrome and glaucoma as well as cone-rod dysfunction on electroretinography. Two patients had normal neuroradiologic findings, emphasizing that some affected individuals have isolated ocular disease. Awareness of the ocular phenotype may aid early diagnosis, appropriate genetic counseling, and monitoring for potential complications. PMID- 27259169 TI - [Editor's Comment]. PMID- 27259168 TI - Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines. AB - Interleukin (IL)-36 cytokines belong to the IL-1 family and include three agonists, IL-36 alpha, beta and gamma and one inhibitor, IL-36 receptor antagonist (IL-36Ra). IL-36 and IL-1 (alpha and beta) activate similar intracellular pathways via their related heterodimeric receptors, IL-36R/IL-1RAcP and IL-1R1/IL-1RAcP, respectively. However, excessive IL-36 versus IL-1 signaling induces different phenotypes in humans, which may be related to differential expression of their respective receptors. We examined the expression of IL-36R, IL-1R1 and IL-1RAcP mRNA in human peripheral blood, tonsil and skin immune cells by RT-qPCR. Monocyte-derived dendritic cells (MDDC), M0, M1 or M2-polarized macrophages, primary keratinocytes, dermal macrophages and Langerhans cells (LC) were stimulated with IL-1beta or IL-36beta. Cytokine production was assessed by RT-qPCR and immunoassays. The highest levels of IL-36R mRNA were found in skin derived keratinocytes, LC, dermal macrophages and dermal CD1a(+) DC. In the blood and in tonsils, IL-36R mRNA was predominantly found in myeloid cells. By contrast, IL-1R1 mRNA was detected in almost all cell types with higher levels in tonsil and skin compared to peripheral blood immune cells. IL-36beta was as potent as IL-1beta in stimulating M2 macrophages, keratinocytes and LC, less potent than IL-1beta in stimulating M0 macrophages and MDDC, and exerted no effects in M1 and dermal macrophages. Levels of IL-1Ra diminished the ability of M2 macrophages to respond to IL-1. Taken together, these data are consistent with the association of excessive IL-36 signaling with an inflammatory skin phenotype and identify human LC and M2 macrophages as new IL-36 target cells. PMID- 27259170 TI - [Threshold ABR Measurements in Anasthesia]. PMID- 27259171 TI - [Inner Ear Hearing Loss]. AB - Hearing loss is one of the most dominant handicaps in modern societies, which additionally very often is not realized or not admitted. About one quarter of the general population suffers from inner ear hearing loss and is therefore restricted in communicational skills. Demographic factors like increasing age play an important role as well as environmental influences and an increasing sound and noise exposure especially in leisure activities. Thus borders between a "classical" presbyacusis - if it ever existed - and envirionmentally induced hearing loss disappear. Today restrictions in hearing ability develop earlier in age but at the same time they are detected and diagnosed earlier. This paper can eventually enlighten the wide field of inner ear hearing loss only fragmentarily; therefore mainly new research, findings and developments are reviewed. The first part discusses new aspects of diagnostics of inner ear hearing loss and different etiologies. PMID- 27259172 TI - [The New E-Health-Act What is imminent to clinics and resident physicians]. PMID- 27259173 TI - [Not Available]. AB - The present article gives an overview of the current state of laryngeal surgery of benign lesions without claiming completeness and with a focus on the ENT board exam. Laryngeal procedures are highly endoscopic and microscopic based. New instruments and high-resolution endoscopic imaging techniques may substitute the typical Kleinsasser approach in the near future. Additionally, new flexible endoscopes may initiate a new era of so-called "office-based surgery". Furthermore, a consistent education of the public about performing vocal hygiene is necessary to prevent the rise of laryngeal diseases. PMID- 27259174 TI - [Not Available]. PMID- 27259175 TI - [Not Available]. PMID- 27259176 TI - Temporal rhythm of petal programmed cell death in Ipomoea purpurea. AB - Flowers are the main sexual reproductive organs in plants. The shapes, colours and scents of corolla of plant flowers are involved in attracting insect pollinators and increasing reproductive success. The process of corolla senescence was investigated in Ipomoea purpurea (Convolvulaceae) in this study. In the research methods of plant anatomy, cytology, cell chemistry and molecular biology were used. The results showed that at the flowering stage cells already began to show distortion, chromatin condensation, mitochondrial membrane degradation and tonoplast dissolution and rupture. At this stage genomic DNA underwent massive but gradual random degradation. However, judging from the shape and structure, aging characteristics did not appear until the early flower senescence stage. The senescence process was slow, and it was completed at the late stage of flower senescence with a withering corolla. We may safely arrive at the conclusion that corolla senescence of I. purpurea was mediated by programmed cell death (PCD) that occurred at the flowering stage. The corolla senescence exhibited an obvious temporal rhythm, which demonstrated a high degree of coordination with pollination and fertilization. PMID- 27259177 TI - The chronic syndromes after previous treatment of pituitary tumours. AB - Ultimately, almost all patients who are appropriately treated for pituitary tumours enter a chronic phase with control or cure of hormonal excess, adequate treatment of pituitary insufficiency and relief of mass effects. This phase is associated with improvement of initial signs and symptoms, but also with the persistent consequences of the initial disease and associated treatments. Pituitary insufficiency is a common denominator in many of these patients, and is associated with a reduction in quality of life, despite adequate endocrine substitution. Hypothalamic dysfunction can be present in patients previously treated for visual impairments caused by large suprasellar adenomas, or craniopharyngiomas. In addition to hypopituitarism, these patients can have multisystem morbidities caused by altered hypothalamic function, including weight gain and disturbed regulation of sleep-wake cycles. Mortality can also be affected. Patients cured of Cushing disease or acromegaly have chronic multisystem morbidities (in the case of Cushing disease, also affecting mortality) caused by irreversible effects of the previous excesses of cortisol in Cushing disease and growth hormone and insulin-like growth factor 1 in acromegaly. In addition to early diagnosis and treatment of pituitary tumours, research should focus on the amenability of these chronic post-treatment syndromes to therapeutic intervention, to improve quality of life and clinical outcomes. PMID- 27259178 TI - Adrenal gland: The genetics of adrenocortical carcinoma revealed. PMID- 27259180 TI - Military teams - A demand for resilience. AB - BACKGROUND: The Royal Norwegian Naval Academy (RNoNA) has an interest in enhancing military teams' knowledge, skills and abilities to deal with complex situations and environments. OBJECTIVE: The objective is to document the need for resilience in military teams and to expand the understanding of how such behavior can be meaningfully instilled through team training interventions. METHOD: Norwegian military subject matter experts (SMEs) assessed the performance of military teams participating in complex military training exercises. Eight cadet teams at the RNoNA were assessed during two separate 4-hour simulator training exercises and a 48-hour live training exercise. RESULTS: Positive Spearman rank correlation coefficients between resilience assessments in the simulator training exercises and the live training exercise were strongest when the simulator scenario emphasized resilience factors inherent in the live exercise, and weakest when the simulator scenario did not facilitate the task demands in the live exercise. CONCLUSION: The study showed that resilience assessed in teams during simulator training exercises predicted their resilient behavior in a subsequent live training exercise and that the proper design of scenario-based simulator training can realistically and effectively represent resilience stressors found in live operations. PMID- 27259179 TI - Developing a workplace resilience instrument. AB - BACKGROUND: Resilience benefits from the use of protective factors, as opposed to risk factors, which are associated with vulnerability. Considerable research and instrument development has been conducted in clinical settings for patients. The need existed for an instrument to be developed in a workplace setting to measure resilience of employees. OBJECTIVE: This study developed and tested a resilience instrument for employees in the workplace. PARTICIPANTS AND METHODS: The research instrument was distributed to executives and nurses working in the United States in hospital settings. Five-hundred-forty completed and usable responses were obtained. The instrument contained an inventory of workplace resilience, a job stress questionnaire, and relevant demographics. The resilience items were written based on previous work by the lead author and inspired by Weick's [1] sense-making theory. RESULTS: A four-factor model yielded an instrument having psychometric properties showing good model fit. Twenty items were retained for the resulting Workplace Resilience Instrument (WRI). Parallel analysis was conducted with successive iterations of exploratory and confirmatory factor analyses. Respondents were classified based on their employment with either a rural or an urban hospital. Executives had significantly higher WRI scores than nurses, controlling for gender. WRI scores were positively and significantly correlated with years of experience and the Brief Job Stress Questionnaire. CONCLUSIONS: An instrument to measure individual resilience in the workplace (WRI) was developed. The WRI's four factors identify dimensions of workplace resilience for use in subsequent investigations: Active Problem-Solving, Team Efficacy, Confident Sense-Making, and Bricolage. PMID- 27259181 TI - Personal resilience and coping Part II: Identifying resilience and coping among U.S. military service members and veterans with implications for work. AB - BACKGROUND: U.S. military personnel face challenging situations including frequent deployments, family separations, and exposure to war. Identifying coping strategies used by the most resilient service members and veterans could positively influence military resiliency training programs. OBJECTIVE: The purposes of this paper are to investigate the relationship between coping and resilience among U.S. military active service members and veterans, to identify the coping strategies used by those considered most resilient, and to discuss coping and resilience as they relate to the workplace. METHODS: U.S. military active service members and veterans (N = 191) completed a demographic survey and two self-report questionnaires: The 14-Item Resilience Scale [1] and the Brief COPE [2]. RESULTS: Active duty service members had higher resilience scores than veterans (p < 0.05), but both fell into the moderate range. Coping strategies were not significantly different between the two groups (p > 0.05). Active service members' resilience was predicted by their use of positive reframing and less use of self-blame as coping strategies, accounting for 52.3% of the variance (R2 = 0.523, F(2, 60) = 32.92, p = 0.000). Veterans' resilience was predicted by longer time-in-service, greater use of humor, and less use of self-blame as coping strategies, explaining 44.8% of the variance (R2 = 0.448, F(3, 116) = 31.408, p = 0.000). CONCLUSIONS: This research identifies the positive coping strategies, and least-used negative coping strategies, of the U.S. service members and veterans in our study population with higher resilience scores. Incorporating this information into military- or veteran-based resilience training is likely to increase training effectiveness. PMID- 27259182 TI - Organizational resilience as a human capital strategy for companies in bankruptcy. AB - BACKGROUND: Bankruptcy is a crisis that generates severe stress and anxiety, resulting in maladaptive behavior and inappropriate decision-making at both individual and organizational levels. There is limited research or guidance for management to address the consequences of bankruptcy on an organization's human capital. OBJECTIVE: This study examined the human capital management principle of organizational resilience that was employed by a company that successfully reorganized and emerged from bankruptcy. METHODS: This study translated seven principles of organizational resilience proposed by Mallak to operationalize a conceptual model of organizational resilience for companies operating in bankruptcy. The model is evaluated using a qualitative research approach comprised of an original case study of Integrated Electrical Services, Inc. RESULTS: The results of the research points to the importance of de-centralized operational decision making, expanding communication channels, ensuring adequate external resources, and engaging external stakeholders in the management of an organization seeking to successfully operate and ultimately emerge from bankruptcy. CONCLUSIONS: The research identified the central importance of expanding decision making boundaries in the resilience of organizations and their ability to adapt when under adverse conditions such as bankruptcy. The implications support an organization developing a human resource strategy to develop organizational resilience. PMID- 27259183 TI - Rapid Detection of Antibiotic Resistance in Gram-Negative Bacteria Through Assessment of Changes in Cellular Morphology. AB - Rapid antimicrobial susceptibility testing has the potential to improve patient outcomes and reduce healthcare-associated costs. In this study, a novel assay based on bacterial cell elongation after exposure to an antibiotic (ceftazidime) was evaluated for its ability to rapidly detect resistance in Gram-negative bacteria. The assay was used to detect resistance in a large collection of strains containing 320 clinical isolates of Acinetobacter baumannii, 171 clinical isolates of Klebsiella pneumoniae, and 212 clinical isolates of Pseudomonas aeruginosa, and the results were compared to those obtained using standard antimicrobial susceptibility testing methods. The assay identified ceftazidime resistant strains with 100% sensitivity and 100% specificity for A. baumannii, 100% sensitivity and 97.2% specificity for K. pneumoniae, and with 82.3% sensitivity and 100% specificity for P. aeruginosa. Importantly, results were obtained in 1 hour 15 minutes from exponentially growing cultures. This study demonstrates that changes in cell length are highly correlated with phenotypic antibiotic susceptibility determined using standard susceptibility testing methods. This study therefore provides proof-of-concept that changes in cell morphology can be used as the basis for rapid detection of antibiotic resistance and provides the basis for the development of novel rapid diagnostics for the detection of antibiotic resistance. PMID- 27259184 TI - Determinants of Exclusive Breast Feeding in sub-Saharan Africa: A Multilevel Approach. AB - BACKGROUND: The study aimed to provide an overall picture of the general pattern of exclusive breast feeding (EBF) in sub-Saharan Africa (SSA) by examining maternal sociodemographic, antenatal and postnatal factors associated with EBF in the region, as well as explore countries variations in EBF rates. METHODS: We utilised cross-sectional data from the Demographic Health Surveys in 27 SSA countries. Our study sample included 25 084 infants under 6 months of age. The key outcome variable was EBF in the last 24 h. Due to the hierarchical structure of the data, a multilevel logistic regression model was used to explore factors associated with EBF. RESULTS: The overall prevalence of EBF in SSA was 36.0%, the prevalence was highest in Rwanda and lowest in Gabon. In the multilevel regression model, factors that were associated with increased likelihood of EBF included secondary and above maternal education, mothers within the ages of 25-34 years, rural residence, richer household wealth quantile, 4+ antenatal care visit, delivering in a health facility, singleton births, female infants, early initiation of breast feeding (EIBF), and younger infants. However, countries with higher gross national income per capita had lower EBF rates. CONCLUSIONS: To achieve a substantial increase in EBF rates in SSA, breast-feeding interventions and policies should target all women but with more emphasis to mothers with younger age, low educational status, urban residence, poor status, multiple births, and male infants. In addition, there is a need to promote antenatal care utilisation, hospital deliveries, and EIBF. PMID- 27259185 TI - Investigation on the difference between biofilm morphologies of the vermifilter and conventional biofilter with the flow cytometer. AB - With the demand of new sludge reduction processes, a vermifilter (VF) was studied based on a conventional biofilter (BF). The biofilm morphology was investigated using a new technique, the flow cytometer (FCM), to find a way to optimize VF structure. VF was inoculated with Eisenia fetida, packed with ceramsites, and operated stably at the organic load of 1.2kg-VSSm(-3)d(-1) with BF as the control. Compared with BF, VF had about 13% more removal efficiency of excess sludge and 45% shorter biofilm update period. FCM profile showed the morphology of microbial cells in VF biofilms was significantly different from that in BF in upper layers, with decreases of average refractive index (about 72%) and size (about 22%), and suggested it was better to keep earthworms there to remove rod shaped microorganisms with other filter media in lower layers to remove spherical ones combining the findings in SEM images and extracellular polymeric substances. PMID- 27259186 TI - Effect of autohydrolysis on the wettability, absorbility and further alkali impregnation of poplar wood chips. AB - Autohydrolysis with different severity factors was performed on poplar wood chips prior to pulping, and the wettability, absorbility and the following impregnation of NaOH solution for the poplar wood chips were then investigated. The results showed that after autohydrolysis pretreatment the porosity, shrinkage and fiber saturation point (FSP) of the poplar wood chips were increased, while the surface contact angle decreased as the severity factor was increased. The autohydrolyzed chips absorbed more NaOH in impregnation that resulted in a low NaOH concentration in the bulk impregnation liquor (i.e., the impregnation liquor outside wood chips), while the concentration in the entrapped liquor (i.e., the impregnation liquor inside wood chips) was increased. Autohydrolysis substantially improved the effectiveness of alkali impregnation. PMID- 27259187 TI - Simultaneous enhancement of methane production and methane content in biogas from waste activated sludge and perennial ryegrass anaerobic co-digestion: The effects of pH and C/N ratio. AB - It is necessary to find an appropriate strategy to simultaneously enhance the methane production and methane content in biogas from waste activated sludge (WAS) and grass co-digestion. In this study an efficient strategy, i.e., adjusting the initial pH 12 and C/N ratio 17/1, for simultaneous enhancement of methane production and methane content in biogas from WAS and perennial ryegrass co-digestion was reported. Experimental results indicated that the maximal methane production was 310mL/gVSadd at the optimum conditions after 30-d anaerobic digestion, which was, respectively, about 1.5- and 3.8-fold of the sole WAS and sole perennial ryegrass anaerobic digestion. Meanwhile, the methane content in biogas was about 74%, which was much higher than that of sole WAS (64%) or sole perennial ryegrass (54%) anaerobic digestion. PMID- 27259188 TI - Techno-economic comparison of biojet fuel production from lignocellulose, vegetable oil and sugar cane juice. AB - In this study, a techno-economic comparison was performed considering three processes (thermochemical, biochemical and hybrid) for production of jet fuel from lignocellulosic biomass (2G) versus two processes from first generation (1G) feedstocks, including vegetable oil and sugar cane juice. Mass and energy balances were constructed for energy self-sufficient versions of these processes, not utilising any fossil energy sources, using ASPEN Plus(r) simulations. All of the investigated processes obtained base minimum jet selling prices (MJSP) that is substantially higher than the market jet fuel price (2-4 fold). The 1G process which converts vegetable oil, obtained the lowest MJSPs of $2.22/kg jet fuel while the two most promising 2G processes- the thermochemical (gasification and Fischer-Tropsch synthesis) and hybrid (gasification and biochemical upgrading) processes- reached MJSPs of $2.44/kg and $2.50/kg jet fuel, respectively. According to the economic sensitivity analysis, the feedstock cost and fixed capital investment have the most influence on the MJSP. PMID- 27259189 TI - Gradient domestication of Haematococcus pluvialis mutant with 15% CO2 to promote biomass growth and astaxanthin yield. AB - In order to increase biomass yield and reduce culture cost of Haematococcus pluvialis with flue gas from coal-fired power plants, a screened mutant by nuclear irradiation was gradually domesticated with 15% CO2 to promote biomass dry weight and astaxanthin yield. The biomass yield of mutant after 10 generations of 15% CO2 domestication increased to 1.3 times as that with air. With the optimization of nitrogen and phosphorus concentration, the biomass dry weight was further increased by 62%. The astaxanthin yield induced with 15% CO2 and high light of 135 MUmol photons m(-2) s(-1) increased to 87.4mg/L, which was 6 times higher than that induced with high light in air. PMID- 27259190 TI - Co-generation of microbial lipid and bio-butanol from corn cob bagasse in an environmentally friendly biorefinery process. AB - Biorefinery process of corn cob bagasse was investigated by integrating microbial lipid and ABE fermentation. The effects of NaOH concentration on the fermentations performance were evaluated. The black liquor after pretreatment was used as substrate for microbial lipid fermentation, while the enzymatic hydrolysates of the bagasse were used for ABE fermentation. The results demonstrated that under the optimized condition, the cellulose and hemicellulose in raw material could be effectively utilized. Approximate 87.7% of the polysaccharides were converted into valuable biobased products (~175.7g/kg of ABE along with ~36.6g/kg of lipid). At the same time, almost half of the initial COD (~48.9%) in the black liquor could be degraded. The environmentally friendly biorefinery process showed promising in maximizing the utilization of biomass for future biofuels production. PMID- 27259191 TI - Removal and biodegradation of naphthenic acids by biochar and attached environmental biofilms in the presence of co-contaminating metals. AB - This study evaluated the efficacy of using a combined biofilm-biochar approach to remove organic (naphthenic acids (NAs)) and inorganic (metals) contaminants from process water (OSPW) generated by Canada's oil sands mining operations. A microbial community sourced from an OSPW sample was cultured as biofilms on several carbonaceous materials. Two biochar samples, from softwood bark (SB) and Aspen wood (N3), facilitated the most microbial growth (measured by protein assays) and were used for NA removal studies performed with and without biofilms, and in the presence and absence of contaminating metals. Similar NA removal was seen in 6-day sterile N3 and SB assays (>30%), while biodegradation by SB associated biofilms increased NA removal to 87% in the presence of metals. Metal sorption was also observed, with up to four times more immobilization of Fe, Al, and As on biofilm-associated biochar. These results suggest this combined approach may be a promising treatment for OSPW. PMID- 27259193 TI - A database of radionuclide activity and metal concentrations for the Alligator Rivers Region uranium province. AB - This paper presents a database of radionuclide activity and metal concentrations for the Alligator Rivers Region (ARR) uranium province in the Australian wet-dry tropics. The database contains 5060 sample records and 57,473 concentration values. The data are for animal, plant, soil, sediment and water samples collected by the Environmental Research Institute of the Supervising Scientist (ERISS) as part of its statutory role to undertake research and monitoring into the impacts of uranium mining on the environment of the ARR. Concentration values are provided in the database for 11 radionuclides (227Ac, 40K, 210Pb, 210Po, 226Ra, 228Ra, 228Th, 230Th, 232Th, 234U, 238U) and 26 metals (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, P, Pb, Rb, S, Sb, Se, Sr, Th, U, V, Zn). Potential uses of the database are discussed. PMID- 27259192 TI - Overcoming organic and nitrogen overload in thermophilic anaerobic digestion of pig slurry by coupling a microbial electrolysis cell. AB - The combination of the anaerobic digestion (AD) process with a microbial electrolysis cell (MEC) coupled to an ammonia stripping unit as a post-treatment was assessed both in series operation, to improve the quality of the effluent, and in loop configuration recirculating the effluent, to increase the AD robustness. The MEC allowed maintaining the chemical oxygen demand removal of the whole system of 46+/-5% despite the AD destabilization after doubling the organic and nitrogen loads, while recovering 40+/-3% of ammonia. The AD-MEC system, in loop configuration, helped to recover the AD (55% increase in methane productivity) and attained a more stable and robust operation. The microbial population assessment revealed an enhancement of AD methanogenic archaea numbers and a shift in eubacterial population. The AD-MEC combined system is a promising strategy for stabilizing AD against organic and nitrogen overloads, while improving the quality of the effluent and recovering nutrients for their reutilization. PMID- 27259194 TI - The dissociability of lexical retrieval and morphosyntactic processes for nouns and verbs: A functional and anatomoclinical study. AB - Nouns and verbs can dissociate following brain damage, at both lexical retrieval and morphosyntactic processing levels. In order to document the range and the neural underpinnings of behavioral dissociations, twelve aphasics with disproportionate difficulty naming objects or actions were asked to apply phonologically identical morphosyntactic transformations to nouns and verbs. Two subjects with poor object naming and 2/10 with poor action naming made no morphosyntactic errors at all. Six of 10 subjects with poor action naming showed disproportionate or no morphosyntactic difficulties for verbs. Morphological errors on nouns and verbs correlated at the group level, but in individual cases a selective impairment of verb morphology was observed. Poor object and action naming with spared morphosyntax were associated with non-overlapping lesions (inferior occipitotemporal and fronto-temporal, respectively). Poor verb morphosyntax was observed with frontal-temporal lesions affecting white matter tracts deep to the insula, possibly disrupting the interaction of nodes in a fronto-temporal network. PMID- 27259195 TI - From Mechanism to Observation and Back Again. PMID- 27259196 TI - Easier, Better, Faster, Stronger: Improved Methods for RNA-Protein Interaction Studies. AB - The RNA field has been revolutionized by methods that allow genome-scale identification of RNA-protein interaction sites. Two reports now introduce more efficient approaches, opening the technology to wider adoption (Van Nostrand et al., 2016; Zarnegar et al., 2016). PMID- 27259197 TI - Visualizing Clonal Evolution in Cancer. AB - Rapid and inexpensive single-cell sequencing is driving new visualizations of cancer instability and evolution. Krzywinski discusses how to present clone evolution plots in order to visualize temporal, phylogenetic, and spatial aspects of a tumor in a single static image. PMID- 27259198 TI - "Cat's Cradling" the 3D Genome by the Act of LncRNA Transcription. AB - There is growing evidence that transcription and nuclear organization are tightly linked. Yet, whether transcription of thousands of long noncoding RNAs (lncRNAs) could play a role in this packaging process remains elusive. Although some lncRNAs have been found to have clear roles in nuclear architecture (e.g., FIRRE, NEAT1, XIST, and others), the vast majority remain poorly understood. In this Perspective, we highlight how the act of transcription can affect nuclear architecture. We synthesize several recent findings into a proposed model where the transcription of lncRNAs can serve as guide-posts for shaping genome organization. This model is similar to the game "cat's cradle," where the shape of a string is successively changed by opening up new sites for finger placement. Analogously, transcription of lncRNAs could serve as "grip holds" for nuclear proteins to pull the genome into new positions. This model could explain general lncRNA properties such as low abundance and tissue specificity. Overall, we propose a general framework for how the act of lncRNA transcription could play a role in organizing the 3D genome. PMID- 27259199 TI - Chromatin Scanning by Dynamic Binding of Pioneer Factors. AB - Pioneer factors such as FoxA target nucleosomal DNA and initiate cooperative interactions at silent genes during development, cellular reprogramming, and steroid hormone induction. Biophysical studies previously showed that the nuclear mobility of FoxA1 is slower than for many other transcription factors, whereas a new single molecule study (Swinstead et al., 2016, Cell) shows comparable chromatin residence times for FoxA1 and steroid receptors. Despite that steroid receptors engage nucleosome-remodeling complexes, the vast majority of co-bound sites with FoxA are dependent upon FoxA, not vice versa. Taken together, the distinguishing feature of pioneer factors remains nucleosomal access rather than an exceptional residence time in chromatin. PMID- 27259200 TI - Chromatin Domains: The Unit of Chromosome Organization. AB - How eukaryotic chromosomes fold inside the nucleus is an age-old question that remains unanswered today. Early biochemical and microscopic studies revealed the existence of chromatin domains and loops as a pervasive feature of interphase chromosomes, but the biological implications of such organizational features were obscure. Genome-wide analysis of pair-wise chromatin interactions using chromatin conformation capture (3C)-based techniques has shed new light on the organization of chromosomes in interphase nuclei. Particularly, the finding of cell-type invariant, evolutionarily conserved topologically associating domains (TADs) in a broad spectrum of cell types has provided a new molecular framework for the study of animal development and human diseases. Here, we review recent progress in characterization of such chromatin domains and delineation of mechanisms of their formation in animal cells. PMID- 27259201 TI - Greater Than the Sum of Parts: Complexity of the Dynamic Epigenome. AB - Information encoded in DNA is interpreted, modified, and propagated as chromatin. The diversity of inputs encountered by eukaryotic genomes demands a matching capacity for transcriptional outcomes provided by the combinatorial and dynamic nature of epigenetic processes. Advances in genome editing, visualization technology, and genome-wide analyses have revealed unprecedented complexity of chromatin pathways, offering explanations to long-standing questions and presenting new challenges. Here, we review recent findings, exemplified by the emerging understanding of crossregulatory interactions within chromatin, and emphasize the pathologic outcomes of epigenetic misregulation in cancer. PMID- 27259202 TI - Interplay between Metabolism and Epigenetics: A Nuclear Adaptation to Environmental Changes. AB - The physiological identity of every cell is maintained by highly specific transcriptional networks that establish a coherent molecular program that is in tune with nutritional conditions. The regulation of cell-specific transcriptional networks is accomplished by an epigenetic program via chromatin-modifying enzymes, whose activity is directly dependent on metabolites such as acetyl coenzyme A, S-adenosylmethionine, and NAD+, among others. Therefore, these nuclear activities are directly influenced by the nutritional status of the cell. In addition to nutritional availability, this highly collaborative program between epigenetic dynamics and metabolism is further interconnected with other environmental cues provided by the day-night cycles imposed by circadian rhythms. Herein, we review molecular pathways and their metabolites associated with epigenetic adaptations modulated by histone- and DNA-modifying enzymes and their responsiveness to the environment in the context of health and disease. PMID- 27259205 TI - DNA Replication-A Matter of Fidelity. AB - The fidelity of DNA replication is determined by many factors, here simplified as the contribution of the DNA polymerase (nucleotide selectivity and proofreading), mismatch repair, a balanced supply of nucleotides, and the condition of the DNA template (both in terms of sequence context and the presence of DNA lesions). This review discusses the contribution and interplay between these factors to the overall fidelity of DNA replication. PMID- 27259204 TI - The Aging Epigenome. AB - During aging, the mechanisms that normally maintain health and stress resistance strikingly decline, resulting in decrepitude, frailty, and ultimately death. Exactly when and how this decline occurs is unknown. Changes in transcriptional networks and chromatin state lie at the heart of age-dependent decline. These epigenomic changes are not only observed during aging but also profoundly affect cellular function and stress resistance, thereby contributing to the progression of aging. We propose that the dysregulation of transcriptional and chromatin networks is a crucial component of aging. Understanding age-dependent epigenomic changes will yield key insights into how aging begins and progresses and should lead to the development of new therapeutics that delay or even reverse aging and age-related diseases. PMID- 27259203 TI - Epigenome Maintenance in Response to DNA Damage. AB - Organism viability relies on the stable maintenance of specific chromatin landscapes, established during development, that shape cell functions and identities by driving distinct gene expression programs. Yet epigenome maintenance is challenged during transcription, replication, and repair of DNA damage, all of which elicit dynamic changes in chromatin organization. Here, we review recent advances that have shed light on the specialized mechanisms contributing to the restoration of epigenome structure and function after DNA damage in the mammalian cell nucleus. By drawing a parallel with epigenome maintenance during replication, we explore emerging concepts and highlight open issues in this rapidly growing field. In particular, we present our current knowledge of molecular players that support the coordinated maintenance of genome and epigenome integrity in response to DNA damage, and we highlight how nuclear organization impacts genome stability. Finally, we discuss possible functional implications of epigenome plasticity in response to genotoxic stress. PMID- 27259206 TI - Replicating Large Genomes: Divide and Conquer. AB - Complete duplication of large metazoan chromosomes requires thousands of potential initiation sites, only a small fraction of which are selected in each cell cycle. Assembly of the replication machinery is highly conserved and tightly regulated during the cell cycle, but the sites of initiation are highly flexible, and their temporal order of firing is regulated at the level of large-scale multi replicon domains. Importantly, the number of replication forks must be quickly adjusted in response to replication stress to prevent genome instability. Here we argue that large genomes are divided into domains for exactly this reason. Once established, domain structure abrogates the need for precise initiation sites and creates a scaffold for the evolution of other chromosome functions. PMID- 27259207 TI - Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire. AB - The life cycle of endogenous retroviruses (ERVs), also called long terminal repeat (LTR) retrotransposons, begins with transcription by RNA polymerase II followed by reverse transcription and re-integration into the host genome. While most ERVs are relics of ancient integration events, "young" proviruses competent for retrotransposition-found in many mammals, but not humans-represent an ongoing threat to host fitness. As a consequence, several restriction pathways have evolved to suppress their activity at both transcriptional and post transcriptional stages of the viral life cycle. Nevertheless, accumulating evidence has revealed that LTR sequences derived from distantly related ERVs have been exapted as regulatory sequences for many host genes in a wide range of cell types throughout mammalian evolution. Here, we focus on emerging themes from recent studies cataloging the diversity of ERV LTRs acting as important transcriptional regulatory elements in mammals and explore the molecular features that likely account for LTR exaptation in developmental and tissue-specific gene regulation. PMID- 27259210 TI - Pharmacokinetics and pharmacodynamics of oral P2Y12 inhibitors during the acute phase of a myocardial infarction: A systematic review. AB - BACKGROUND: The immediate administration of oral antiplatelet therapy in the form of aspirin plus a P2Y12 inhibitor is the universally recognised standard of care for patients who present with acute myocardial infarction. Despite strong recommendations for their use, there are a paucity of data describing their onset of action and clinical efficacy during the short time frames from confirmation of diagnosis to reperfusion with primary percutaneous coronary intervention. OBJECTIVES: To complete a systematic review evaluating the currently available evidence regarding the pharmacokinetic and pharmacodynamic activity of orally administered clopidogrel, prasugrel and ticagrelor during the acute phase of a myocardial infarction in relation to mechanical reperfusion with primary percutaneous coronary angioplasty. METHODS: We searched PubMed and EMBASE databases up to January 2016 using the terms outlined in our search strategy. RESULTS: Twelve papers were included in our final analysis; seven relating to pharmacodynamic studies, one to a pharmacokinetic study and four to pharmacokinetic/pharmacodynamic studies. CONCLUSION: Our results indicate that despite the administration of oral P2Y12 inhibitors including newer more potent agents that should allow for greater and more consistent levels of platelet inhibition, the physiological state of ST segment elevation MI (STEMI) and the co administration of opioid based analgesia are associated with a reduction in the degree of platelet inhibition achieved following their administration. PMID- 27259211 TI - [Immunological mechanisms involved in obesity and their role in metabolic syndrome]. AB - In the past 50 years, the occurrence of human obesity has risen dramatically across the globe. The WHO reported that at least 1.9 billion (1.9 * 10(9)) adults are overweight and 600 million are obese, and the numbers are expected to rise dramatically in the future without intervention. The recent increase in human obesity is caused by increased energy intake and reduced energy expenditure that results in a massive increase in adipose tissue, which is generally harmful to our health. Indeed, the increase in human obesity is strongly associated with an increase in many diseases such as type 2 diabetes (T2D), biliary disease, cardiovascular disease, hepatic steatosis, airway disease, neurodegeneration and certain cancers. The metabolic and immune systems are closely linked and functionally dependent. As a result, excessive nutrient consumption associated with obesity can be recognized as a harmful, stress-inducing biological event by innate pattern recognition receptors (PRRs). This activates inflammatory and stress responses in various metabolic tissues, leading to the chronic low-grade inflammation called metabolic inflammation or "metainflammation". Adipose tissue is mainly composed of adipocytes, although other cell types contribute to its growth and function, including pre-adipocytes, macrophages, lymphocytes, fibroblasts and vascular cells. Obesity can result in profound changes in the cell composition of fat tissue and can lead to the modulation of individual cell phenotypes. Many factors are involved in development of metainflammation, including hypoxia of adipocytes, oxidative stress, endoplasmic reticulum stress, activation of inflammasomes, adipocyte death, activation of TLR and abnormal gut flora. PMID- 27259212 TI - Evaluation of effect of selected trace elements on dynamics of sperm DNA fragmentation. AB - INTRODUCTION: Lead and cadmium can lead to negative effects on sperm chromatin DNA integrity. Copper, zinc and selenium are essential components of many enzymes which are important for reproduction. The aim of this research was to evaluate the influence of lead, cadmium, zinc, copper and selenium on the dynamics of semen DNA fragmentation. MATERIAL AND METHODS: The present study concerned 85 fertile and 131 infertile men aged 25-35. DNA fragmentation in the samples was determined after 3 h, 6 h and 12 h. The Pb, Cd, Cu, Zn, and Se measurements were performed by the electrothermal-atomic absorption spectrometry method. RESULTS: We found that sperm DNA fragmentation was a dynamic process which was intensified with an increase in the level of lead in seminal plasma. The levels of lead and cadmium were higher in seminal plasma of infertile men, compared to fertile men. The levels of zinc, copper and selenium in seminal plasma were higher in men with proven fertility, compared to infertile men, and did not exert a significant effect on the dynamics of sperm DNA fragmentation. The level of cadmium had no significant effect on intensification of sperm DNA fragmentation in time. DISCUSSION: Reports in the literature which concern the effect of trace elements on human reproduction are equivocal. The present study confirmed an unfavourable effect, especially that of lead, on the dynamics of sperm DNA fragmentation; however, these studies need to be expanded and continued in the future. PMID- 27259208 TI - When Genome Maintenance Goes Badly Awry. AB - Genetic abnormalities are present in all tumor types, although the frequency and type can vary. Chromosome abnormalities include highly aberrant structures, particularly chromothriptic chromosomes. The generation of massive sequencing data has illuminated the scope of the mutational burden in cancer genomes, identifying patterns of mutations (mutation signatures), which have the potential to shed light on the relatedness and etiologies of cancers and impact therapy response. Some mutation patterns are clearly attributable to disruptions in pathways that maintain genomic integrity. Here we review recent advances in our understanding of genetic changes occurring in cancers and the roles of genome maintenance pathways. PMID- 27259213 TI - [Viral transfer of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in gene therapy]. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces carcinoma cell death through the extrinsic pathway of apoptosis. Preclinical trials of gene therapy have been conducted using viral transfer of the TRAIL transgene into prostate, bladder, breast, kidney, liver, non-small cell lung cancer and also glioblastoma cells. Experiments in vitro demonstrated the extensive apoptosis of target cells as well as frequent disease regression or remission. TRAIL transfer did not show any side effects, opposite to chemotherapy. Encouraging results of TRAIL-related gene therapy were observed in rheumatoid arthritis and type 1 diabetes. Adenoviral vectors (AdV) encoding TRAIL are the most promising tool in anti-tumor therapy. They have undergone numerous modifications by increasing transfection efficiency and transgene expression in target cells. However, only one clinical phase I trial has been performed. AdV encoding the TRAIL transgene caused local inflammation and apoptosis in patients with prostate cancer. PMID- 27259214 TI - [Multifunctional ligands--a new approach in the search for drugs against multi factorial diseases]. AB - Selective drugs directed at a single biological target often prove ineffective in the treatment of diseases with a complex pathomechanism, e.g. Alzheimer's disease (AD). This situation prompts researchers to design multi-target-directed ligands (MTDLs), capable of interacting with a number of selected biological targets. The paper outlines the concept of the multi-target-directed ligand design and examples of its use in the search of a cure for AD. In the knowledge-based approach for designing MTDLs, selective ligands of different targets are combined in one molecule. In the screening-based approach, libraries of compounds are screened against selected targets, which allows one to find molecules with a desirable pharmacological profile. It is also possible to obtain multifunctional ligands by performing optimization of a drug with known side activity and transforming it into the main activity, with a simultaneous decrease or complete removal of the original activity. The type of biological targets and applied MTDL design strategy affect the physicochemical and pharmacokinetic properties of the resulting molecules. AD is a multifactorial neurodegenerative disease of the central nervous system associated with the formation of neurofibrillary tangles within neurons, formed by the hyperphosphorylated tau proteins, and extracellular beta-amyloid deposits (senile plaques). Current AD therapy comprises symptomatic drugs that enhance cholinergic neurotransmission or inhibit glutamate receptors. The literature provides numerous examples of compounds which proved in in vitro tests to be multifunctional ligands. Most of them are derivatives of cholinesterase-inhibiting drugs, also capable of inhibiting the aggregation of Abeta and showing neuroprotective effects in Abeta-induced cytotoxicity assays. PMID- 27259209 TI - What's Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Nondeterminism. AB - The field of single-cell biology has morphed from a philosophical digression at its inception, to a playground for quantitative biologists, to a major area of biomedical research. The last several years have witnessed an explosion of new technologies, allowing us to apply even more of the modern molecular biology toolkit to single cells. Conceptual progress, however, has been comparatively slow. Here, we provide a framework for classifying both the origins of the differences between individual cells and the consequences of those differences. We discuss how the concept of "random" differences is context dependent, and propose that rigorous definitions of inputs and outputs may bring clarity to the discussion. We also categorize ways in which probabilistic behavior may influence cellular function, highlighting studies that point to exciting future directions in the field. PMID- 27259215 TI - Assessment of peripheral blood and bone marrow T, NK, NKT and dendritic cells in patients with multiple myeloma. AB - Symptoms of multiple myeloma (MM) include bone destruction with pathological fractures, kidney failure and frequent infections, which are the major causes of patient mortality. In our recent research, we demonstrated that the degree of dendritic cell (DC) subpopulation deficit could be related to MM progression, which in consequence may contribute to the MM-related impairment of the immune responses. In the present study, we determined by flow cytometry the frequencies of CD4+ and CD8+ T cells, NK, and NKT-like cells as well as their correlation with myeloid and lymphoid populations of DCs in patients with MM. The study involved 50 patients diagnosed with MM at the Department of Hematology in the Holycross Cancer Center in Kielce. The research samples were collected after the MM diagnosis and before the initiation of anticancer therapy. The obtained results revealed the relations between the percentages of DC subpopulations and lymphocyte subsets, especially the activated ones, in the peripheral blood (PB) and bone marrow (BM). The described role of DCs in the process of the immunological response, either adaptive or innate, leads us to conclude that the decrease of the number or percentage of these cells may have a negative impact on the process of activation of effector cells and, consequently, on the effectiveness of a response to foreign as well as neoplastic antigens in patients with MM. PMID- 27259216 TI - [Proteasome inhibitors in cancer therapy]. AB - Proteasomes are multisubunit enzyme complexes. They contain three enzymatic active sites which are termed chymotrypsin-like, trypsin-like, and caspase-like. The elementary function of the proteasomes is degradation of damaged proteins. Proteasome inhibition leads to accumulation of damaged protein, which leads to caspase activation and cell death. This relationship is used in cancer therapy. Bortezomib is the first proteasome inhibitor approved by the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma. Carfilzomib belongs to the second generation of drugs, which was approved by the US FDA in 2012. Currently in the study phase there are four new inhibitors: ixazomib (MLN9780/MLN2238), delanzomib (CEP-18770), oprozomib (ONX0912/PR-047) and marizomib (NPI-0052). PMID- 27259217 TI - [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain]. AB - Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells. PMID- 27259218 TI - [Glucuronidation of antitumour therapeutics--detoxification, mechanism of resistance or prodrug formation?]. AB - The physiological role of phase I and II of xenobiotic biotransformations is their detoxification and better excretion outside the organism. UDP glucuronosyltransferases (UGTs) being the enzymes of phase II metabolism catalyse the conjugation of glucuronic acid to the lipophilic substrate by its specific nucleophilic group. UGT isoenzymes of various substrate specificities and different expression profiles in selected tissues belong to the large UGT superfamily. Usually, glucuronidation is the detoxification process, but sometimes (morphine, tamoxifen) glucuronides express biological activity higher than or comparable to the native compound. The level of UGT gene expression is individual for patients, because of their genetic status as well as epigenetic conditions. Also, xenobiotics are able to modulate UGT level and gene expression by the interaction with nuclear receptors. Moreover, one can find a lower level of UGT in the tumour compared to normal tissue, which results in the protection against deactivation of the drug and in the promotion of its selective activity in tumor tissue. On the other hand, UGT activity is considered as the possible cause of resistance to chemotherapy. Metabolism by hepatic and intestinal UGT isoenzymes is responsible for the "first-pass effect", whereas acquired resistance consists in the induction of UGT gene expression by the chemotherapeutic or its metabolite. Moreover, UGT induction can be associated with the induction of membrane transporters, particularly proteins of the ABC family, responsible for drug excretion outside the cell. The above resistance effects can be fortified by the overexpression of selected UGT isoenzymes sometimes observed in specific types of tumours. It is also considered that many advanced tumours are characterized by a higher level of beta-glucuronidase. This enzyme has a chance to be the molecular target of directed antitumour therapy, as it catalyses beta-glucuronide hydrolysis, leading to active aglycones. PMID- 27259219 TI - Green tea extract induces protective autophagy in A549 non-small lung cancer cell line. AB - BACKGROUND AND OBJECTIVES: For many decades, polyphenols, including green tea extract catechins, have been reported to exert multiple anti-tumor activities. However, to date the mechanisms of their action have not been completely elucidated. Thus, the aim of this study was to assess the effect of green tea extract on non-small lung cancer A549 cells. MATERIAL AND METHODS: A549 cells following treatment with GTE were analyzed using the inverted light and fluorescence microscope. In order to evaluate cell sensitivity and cell death, the MTT assay and Tali image-based cytometer were used, respectively. Ultrastructural alterations were assessed using a transmission electron microscope. RESULTS: The obtained data suggested that GTE, even at the highest dose employed (150 MUM), was not toxic to A549 cells. Likewise, the treatment with GTE resulted in only a very small dose-dependent increase in the population of apoptotic cells. However, enhanced accumulation of vacuole-like structures in response to GTE was seen at the light and electron microscopic level. Furthermore, an increase in the acidic vesicular organelles and LC3-II puncta formation was observed under the fluorescence microscope, following GTE treatment. The analysis of the functional status of autophagy revealed that GTE induced autophagy may provide self-protection against its own cytotoxicity, since we observed that the blockage of autophagy by bafilomycin A1 decreased the viability of A549 cells and potentiated necrotic cell death induction in response to GTE treatment. CONCLUSION: Collectively, our results revealed that A549 cells are insensitive to both low and high concentrations of the green tea extract, probably due to the induction of cytoprotective autophagy. These data suggest that a potential utility of GTE in lung cancer therapy may lie in its synergistic combinations with drugs or small molecules that target autophagy, rather than in monotherapy. PMID- 27259220 TI - [Extracellular matrix as a microbial virulence factor in the development of human diseases]. AB - Extracellular polymers which build a biofilm matrix possess a complicated structure, where the polysaccharide fraction, composed of homo- or heteropolysaccharides, is the largest. Other important components are proteins, eDNA, glycoproteins and lipids. The matrix has a protective function against the surrounding environment, plays a role in biofilm formation and maturation processes, stabilizes the biofilm structure, and also is a source of nutrients and water for the cells. It is noteworthy that the biofilm matrix is a virulence factor and plays an important role in the pathogenesis of many human diseases. Pseudomonas aeruginosa growing in the lungs of patients with cystic fibrosis produces three major exopolysaccharides (Pel, Psl and alginate) and synthesizes numerous proteins such as lectins and enzymes, e.g. PasP, chitinase, aminopeptidase, and protease IV, which facilitate the tissue colonization. Extracellular polymers play a significant role in the course of caries, which is associated with the development of multi-species biofilm on the teeth surface. The structure of the matrix surrounding that biofilm is complicated--different for each patient. The components of the matrix are constantly changing depending on the environmental conditions, e.g. the presence of sucrose affects the synthesis of mutan and dextran. Infections associated with biofilm formation on implants pose significant medical and economic problems. The main components of the matrices are saccharides (e.g., PIA, EC-TA), as well as surface and extracellular proteins. Studies on the matrix structure and the factors regulating its synthesis are necessary to develop techniques for biofilm eradication and better control of biofilm-related infections. PMID- 27259221 TI - MSX1 gene in the etiology orofacial deformities. AB - The muscle segment homeobox (MSX1) gene plays a crucial role in epithelial mesenchymal tissue interactions in craniofacial development. It plays a regulative role in cellular proliferation, differentiation and cell death. The human MSX1 domain was also found in cow (Bt 302906), mouse (Mm 123311), rat (Rn13592001), chicken (Gg 170873) and clawed toad (XI 547690). Cleft lip and palate is the most common anomaly of the facial part of the skull. The etiology is not fully understood, but it is believed that the key role is played by the genetic factor activated by environmental factors. Among the candidate genes whose mutations could lead to formation of the cleft, the MSX1 homeobox gene is mentioned. Mutations in the gene MSX1 can lead to isolated cleft deformities, but also cause other dismorphic changes. Among the most frequently mentioned is loss of permanent tooth buds (mostly of less than 4 teeth - hypodontia, including second premolars). Mutations of MSX1 are observed in the Pierre- Robin sequence, which may be one of the features of congenital defects or is observed as an isolated defect. Mutation of the gene can lead to the occurrence of a rare congenital defect Wiktop (dental-nail) syndrome. Deletion of a fragment MSX1 (4p16.3) located in the WHS critical region, may be a cause of some symptoms of Wolf-Hirschhorn syndrome. PMID- 27259222 TI - [Osteoprotegerin as a marker of atherosclerosis and a prognostic factor in stroke]. AB - Stroke is one of the most common causes of disability and lack of independence in activities of daily living in adults. One of the most important factors predisposing to stroke, besides hypertension and atrial fibrillation, is carotid atherosclerosis. Rupture of unstable plaque with formation of a platelet plug is the cause of about 20-25% of ischemic strokes. Osteoprotegerin (OPG) is an important regulator of bone remodeling under physiological and disease conditions, as well as the regulator of osteoclast differentiation. Elevated plasma OPG level is associated with increased risk of ischemic stroke and heart diseases, including atrial fibrillation, and is observed in patients with symptomatic carotid artery stenosis and atherosclerotic vulnerable plaques. Furthermore, the occurrence of certain genotypes of OPG is 10 times more common in people with unstable atherosclerotic plaque, making them an independent risk predictor of plaque instability. This article summarizes the current state of knowledge on the potential role of OPG as a biomarker and prognostic indicator of stroke. PMID- 27259223 TI - Nuclear factor kappaB inhibitor BAY 11-7082 suppresses oxidative stress induced by endothelin-1 (ET-1) in rat kidney. AB - AIM: The aim of the study was to evaluate the effect of BAY 11-7082, an NF-kappaB inhibitor, on basal and ET-1-induced production of reactive oxygen species (ROS), TNF-alpha and p65 protein in rat kidney. MATERIAL/METHODS: The experimental animals were divided into five groups (n=7) receiving: 1) saline (control); 2 and 3) ET-1 in a dose of 3 MUg/kg body weight (b.w.) or 12.5 MUg/kg b.w.; 4) BAY 11 7082 (10 mg/kg b.w.); 5) BAY 11-7082 (10 mg/kg b.w.) and ET-1 (12.5 MUg/kg b.w.), respectively. In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, TNF-alpha, p65 protein and GSH/GSSG ratio were determined. RESULTS: ET-1 resulted in a dose-dependent increase in TBARS and hydrogen peroxide (H2O2) levels, and a decrease in GSH/GSSG ratio when compared to the controls. BAY 11-7082 administered 1 h before ET-1 administration at a dose of 12.5 MUg/kg resulted in a decrease (P<0.001) in TBARS and H2O2 levels and an increase (P<0.001) in GSH/GSSG ratio compared to the ET-1 groups. The level of TNF-alpha was increased (P<0.001) in the presence of ET-1, while BAY 11-7082 reduced the TNF-alpha level (P<0.001). The rats receiving BAY 11-7082 showed a decrease in NF-kappaB p65 protein level in the nuclear fraction and an increase in the cytoplasmic fraction. CONCLUSIONS: The results suggest that BAY 11-7082 plays a protective role against ET-1 induced oxidative stress in kidney tissue. These actions of BAY 11-7082 may result from reduced activity of NF-kappaB signaling pathways. Inhibition of the NF-kappaB pathway may be a promising strategy for preventing the progression of kidney damage. PMID- 27259224 TI - [From malaria parasite point of view--Plasmodium falciparum evolution]. AB - Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium, which have arguably exerted the greatest selection pressure on humans in the history of our species. Besides humans, different Plasmodium parasites infect a wide range of animal hosts, from marine invertebrates to primates. On the other hand, individual Plasmodium species show high host specificity. The extraordinary evolution of Plasmodium probably began when a free-living red algae turned parasitic, and culminated with its ability to thrive inside a human red blood cell. Studies on the African apes generated new data on the evolution of malaria parasites in general and the deadliest human-specific species, Plasmodium falciparum, in particular. Initially, it was hypothesized that P. falciparum descended from the chimpanzee malaria parasite P. reichenowi, after the human and the chimp lineage diverged about 6 million years ago. However, a recently identified new species infecting gorillas, unexpectedly showed similarity to P. falciparum and was therefore named P. praefalciparum. That finding spurred an alternative hypothesis, which proposes that P. falciparum descended from its gorilla rather than chimp counterpart. In addition, the gorilla-to-human host shift may have occurred more recently (about 10 thousand years ago) than the theoretical P. falciparum-P. reichenowi split. One of the key aims of the studies on Plasmodium evolution is to elucidate the mechanisms that allow the incessant host shifting and retaining the host specificity, especially in the case of human specific species. Thorough understanding of these phenomena will be necessary to design effective malaria treatment and prevention strategies. PMID- 27259225 TI - [Autoimmune connective tissue diseases and vaccination]. AB - The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group. PMID- 27259226 TI - The influence of a nitric oxide synthase inhibitor and endothelin receptor blocker on the free sulfhydryl groups content in lung homogenates. AB - INTRODUCTION: The aim of the study was to assess the influence of the nitric oxide synthase inhibitor L-NAME and the endothelin receptor blocker BQ123 on the free sulfhydryl (-SH) groups content in rat lung homogenates. MATERIAL AND METHODS: Experiments were performed on Wistar-Kyoto rats divided into the following groups: group I (control) received (i.v.) saline; group II (ET-1) received (i.v.) endothelin 1 (3 g MUg/kg b.w.); group III (BQ123+ET-1) received (i.v.) ET(A) receptor blocker (1 mg/kg b.w.) + endothelin 1 (3 g MUg/kg b.w.); group IV (L-NAME+ET-1) received (i.v.) nitric oxide synthase inhibitor (5 mg/kg b.w.) + endothelin 1 (3 MUg/kg b.w.). RESULTS: Administration of BQ123 at a dose of 1 mg/kg b.w. resulted in a statistically significant increase in the concentration of -SH groups (p<0.001 vs. ET-1). L-NAME (5 mg/kg b.w.) also significantly increased the level of -SH groups in the lungs of rats during oxidative stress induced ET-1 (p<0.001). DISCUSSION: The nitric oxide synthase inhibitor L-NAME at a dose of 5 mg/kg b.w. and the endothelin receptor blocker BQ123 at a dose of 1 mg/kg b.w. showed a significant increase in the concentration of -SH groups in the lungs, which may be associated with an increase in synthesis of proteins containing sulfhydryl groups. PMID- 27259227 TI - Role of collagen type IV in the pathogenesis of increased prenasal thickness in Down syndrome fetuses: sonographic and immunohistological findings. AB - OBJECTIVE: The present study aims to compare the presence and localization of collagen type IV in the prenasal tissue of fetuses with and without Down syndrome (DS). METHODS: Products of conception were obtained from mid-gestation uterine evacuations of 14 DS fetuses and 15 unaffected controls. Microdissection of the prenasal area and an analysis of the prenasal tissue specimens were performed by a single pathologist, blinded to the karyotype results. Immunohistological presence and localization of type IV collagen were analyzed in the basement membrane (BM), blood vessels, and stroma of the tissues. RESULTS: There were no statistically significant differences in the presence and localization of antibodies for collagen IV in the blood vessels and stroma between the two groups. However, the presence and localization of type IV collagen in the BM of the prenasal skin were significantly higher in DS specimens compared to the control group (P=0.023). When combining both groups altogether, a significant correlation was found between the increased prenasal thickness (PT) and the high presence and location of collagen type IV, irrespective of the karyotype results (Spearman's correlation; R=0.459; P=0.012). CONCLUSION: Using the immunohistochemistry technique, we were able to confirm the overexpression of collagen type IV in the BM of the prenasal area. This may explain the sonographic finding of increased PT seen mainly in DS fetuses. PMID- 27259228 TI - Corrigendum to: Exposure to sunshine early in life prevented development of type 1 diabetes in Danish boys. PMID- 27259229 TI - Hypoglycemic activity of Gleditsia caspica extract and its saponin-containing fraction in streptozotocin-induced diabetic rats. AB - The fruits of Gleditsia species (Fabaceae) have been known in traditional medicine as a saponin-rich herbal medicine. The present study aimed to investigate the effects of the total methanolic extract of Gleditsia caspica (MEGC) and its saponin-containing fractions (SFGC) on hyperglycemia in streptozotocin (STZ)-induced diabetic rats. A single intraperitoneal injection of STZ (55 mg/kg body weight) was used to induce hyperglycemia in male albino rats. MEGC (15, 30 and 60 mg/kg, p.o.) and SFGC (15, 30 and 60 mg/kg, p.o.) were administered to the diabetic rats daily for 14 days. The anti-diabetic drug gliclazide (10 mg/kg, p.o.) was used as a positive control. Blood samples were collected from overnight fasted rats for the evaluation of the antihyperglycemic, antihyperlipidemic and antioxidant activities. The levels of glucose, triglycerides (TG), cholesterol (TC) and malondialdehyde (MDA) were increased significantly, whereas the levels of alpha-amylase, insulin and reduced glutathione (GSH) were decreased in the experimental diabetic rats. Pancreas and liver of the diabetic rats exhibited significant changes in the histopathology, morphology and DNA content. Administration of MEGC or SFGC led to a decrease in the levels of glucose, TG, TC and MDA. In addition, the levels of alpha-amylase, insulin and GSH were increased in MEGC and SFGC treated diabetic rats. Also, the histopathological and morphological changes, as well the changes in DNA were significantly reversed by the extracts. Thus, MEGC and SFGC exhibited potent hypoglycemic and hypolipidemic activities in STZ- induced diabetic rats. PMID- 27259230 TI - Theranos phenomenon - part 4: Theranos at an International Conference. PMID- 27259232 TI - Characterization and use of HapT1-derived homologous tumors as a preclinical model to evaluate therapeutic efficacy of drugs against pancreatic tumor desmoplasia. AB - Desmoplasia in human pancreatic cancer (PC) promotes cancer progression and hinders effective drug delivery. The objectives of this study were to characterize a homologous orthotopic model of PC in Syrian golden hamster and investigate the effect of anti-fibrotic (pirfenidone), antioxidant (N-acetyl cysteine, NAC) and anti-addiction (disulfiram, DSF) drugs on desmoplasia and tumor growth in this model. The HapT1 PC cells when implanted orthotopically into hamsters formed tumors with morphological, cellular and molecular similarities to human PC. Protein profiling of activated hamster pancreatic stellate cells (ha PSCs) revealed expression of proteins involved in fibrosis, cancer cells growth and metastasis. Pirfenidone, suppressed growth of HapT1 cells and the desmoplastic response in vivo; these effects were enhanced by co-administration of NAC. Disulfiram alone or in combination with copper (Cu) was toxic to HapT1 cells and PSCs in vitro; but co-administration of DSF and Cu accelerated growth of HapT1 cells in vivo. Moreover, DSF had no effect on tumor-associated desmoplasia. Overall, this study identifies HapT1-derived orthotopic tumors as a useful model to study desmoplasia and tumor-directed therapeutics in PC. Pirfenidone in combination with NAC could be a novel combination therapy for PC and warrants investigation in human subjects. PMID- 27259231 TI - Diagnostic value of microRNAs in asbestos exposure and malignant mesothelioma: systematic review and qualitative meta-analysis. AB - BACKGROUND: Asbestos is a harmful and exceptionally persistent natural material. Malignant mesothelioma (MM), an asbestos-related disease, is an insidious, lethal cancer that is poorly responsive to current treatments. Minimally invasive, specific, and sensitive biomarkers providing early and effective diagnosis in high-risk patients are urgently needed. MicroRNAs (miRNAs, miRs) are endogenous, non-coding, small RNAs with established diagnostic value in cancer and pollution exposure. A systematic review and a qualitative meta-analysis were conducted to identify high-confidence miRNAs that can serve as biomarkers of asbestos exposure and MM. METHODS: The major biomedical databases were systematically searched for miRNA expression signatures related to asbestos exposure and MM. The qualitative meta-analysis applied a novel vote-counting method that takes into account multiple parameters. The most significant miRNAs thus identified were then subjected to functional and bioinformatic analysis to assess their biomarker potential. RESULTS: A pool of deregulated circulating and tissue miRNAs with biomarker potential for MM was identified and designated as "mesomiRs" (MM associated miRNAs). Comparison of data from asbestos-exposed and MM subjects found that the most promising candidates for a multimarker signature were circulating miR-126-3p, miR-103a-3p, and miR-625-3p in combination with mesothelin. The most consistently described tissue miRNAs, miR-16-5p, miR-126-3p, miR-143-3p, miR-145-5p, miR-192-5p, miR-193a-3p, miR-200b-3p, miR-203a-3p, and miR-652-3p, were also found to provide a diagnostic signature and should be further investigated as possible therapeutic targets. CONCLUSION: The qualitative meta-analysis and functional investigation confirmed the early diagnostic value of two miRNA signatures for MM. Large-scale, standardized validation studies are needed to assess their clinical relevance, so as to move from the workbench to the clinic. PMID- 27259233 TI - Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT. AB - The Rab GTPases regulate vesicular trafficking machinery that transports and delivers a diverse pool of cargo, including growth factor receptors, integrins, nutrient receptors and junction proteins to specific intracellular sites. The trafficking machinery is indeed a major posttranslational modifier and is critical for cellular homeostasis. Deregulation of this stringently controlled system leads to a wide spectrum of disorders including cancer. Herein we demonstrate that Rab25, a key GTPase, mostly decorating the apical recycling endosome, is a dichotomous variable in breast cancer cell lines with higher mRNA and protein expression in Estrogen Receptor positive (ER+ve) lines. Rab25 and its effector, Rab Coupling Protein (RCP) are frequently coamplified and coordinately elevated in ER+ve breast cancers. In contrast, Rab25 levels are decreased in basal-like and almost completely lost in claudin-low tumors. This dichotomy exists despite the presence of the 1q amplicon that hosts Rab25 across breast cancer subtypes and is likely due to differential methylation of the Rab25 promoter. Functionally, elevated levels of Rab25 drive major hallmarks of cancer including indefinite growth and metastasis but in case of luminal B breast cancer only. Importantly, in such ER+ve tumors, coexpression of Rab25 and its effector, RCP is significantly associated with a markedly worsened clinical outcome. Importantly, in claudin-low cell lines, exogenous Rab25 markedly inhibits cell migration. Similarly, during Snail-induced epithelial to mesenchymal transition (EMT) exogenous Rab25 potently reverses Snail-driven invasion. Overall, this study substantiates a striking context dependent role of Rab25 in breast cancer where Rab25 is amplified and enhances aggressiveness in luminal B cancers while in claudin-low tumors, Rab25 is lost indicating possible anti-tumor functions. PMID- 27259234 TI - A novel arylbenzofuran induces cervical cancer cell apoptosis and G1/S arrest through ERK-mediated Cdk2/cyclin-A signaling pathway. AB - 7-hydroxy-5,4'-dimethoxy-2-arylbenzofuran (Ary) is purified from Livistona. It has been demonstrated to have anticancer activity to various tumors in including cervical cancer, but its mechanism is still unclear. In the present, we show that Ary induces cervical cancer cells apoptosis through mitochondria degradation and mediates cervical cancer cell arrest. Further, Ary-inducing cell cycle G1/S-phase arrest is associated with increased cyclin A2 and cyclin dependent kinase 2 (Cdk2) proteins. Knockdown of cyclin A2 using small interfering RNA (siRNA), and inhibiting Cdk2 activity with flavopiridol, strikingly reduced G1/S-phase arrest. Moreover, Ary sustainedly induced phosphorylation of extracellular signal regulated kinase1/2 (ERK1/2). And ERK1/2 phosphorylation inhibition using specific inhibitor U0126 effectively suppressed cyclin A2 expression, and reduced G1/S-phase arrest induced by Ary. All the experiments in vitro and in vivo verified that Ary has an anticancer effect on cervical cancer. These data provide novel evidences that Ary induces cervical cancer cells apoptosis through mitochondria degradation and cell G1/S-phase arrest. These findings also suggest that ERK-mediated Cdk2/cyclin A signaling pathway is involved in Ary-induced G1/S phase arrest. PMID- 27259235 TI - Germline BRCA1 mutation reprograms breast epithelial cell metabolism towards mitochondrial-dependent biosynthesis: evidence for metformin-based "starvation" strategies in BRCA1 carriers. AB - We hypothesized that women inheriting one germline mutation of the BRCA1 gene ("one-hit") undergo cell-type-specific metabolic reprogramming that supports the high biosynthetic requirements of breast epithelial cells to progress to a fully malignant phenotype. Targeted metabolomic analysis was performed in isogenic pairs of nontumorigenic human breast epithelial cells in which the knock-in of 185delAG mutation in a single BRCA1 allele leads to genomic instability. Mutant BRCA1 one-hit epithelial cells displayed constitutively enhanced activation of biosynthetic nodes within mitochondria. This metabolic rewiring involved the increased incorporation of glutamine- and glucose-dependent carbon into tricarboxylic acid (TCA) cycle metabolite pools to ultimately generate elevated levels of acetyl-CoA and malonyl-CoA, the major building blocks for lipid biosynthesis. The significant increase of branched-chain amino acids (BCAAs) including the anabolic trigger leucine, which can not only promote protein translation via mTOR but also feed into the TCA cycle via succinyl-CoA, further underscored the anabolic reprogramming of BRCA1 haploinsufficient cells. The anti diabetic biguanide metformin "reversed" the metabolomic signature and anabolic phenotype of BRCA1 one-hit cells by shutting down mitochondria-driven generation of precursors for lipogenic pathways and reducing the BCAA pool for protein synthesis and TCA fueling. Metformin-induced restriction of mitochondrial biosynthetic capacity was sufficient to impair the tumor-initiating capacity of BRCA1 one-hit cells in mammosphere assays. Metabolic rewiring of the breast epithelium towards increased anabolism might constitute an unanticipated and inherited form of metabolic reprogramming linked to increased risk of oncogenesis in women bearing pathogenic germline BRCA1 mutations. The ability of metformin to constrain the production of mitochondrial-dependent biosynthetic intermediates might open a new avenue for "starvation" chemopreventive strategies in BRCA1 carriers. PMID- 27259236 TI - JARID2 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition through PTEN/AKT signaling. AB - JARID2 is crucial for maintenance of pluripotency and differentiation of embryonic stem cells. However, little is known about the role of JARID2 in metastasis of hepatocellular carcinoma (HCC). This study found that JARID2 expression was significantly higher in HCC tissues than that in adjacent non tumor liver tissues (ANLTs), and its expression level correlated with HCC metastasis. High JARID2 expression was significantly correlated with multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05) and indicated poor prognosis of HCC in training and validation cohorts (all P < 0.05) totaling 182 patients. High JARID2 expression was an independent and significant risk factor for disease-free survival (DFS; P = 0.017) and overall survival (OS; P = 0.041) after curative liver resection in training cohort, and also validated as an independent and significant risk factor for DFS (P = 0.033) and OS (P = 0.031) in validation cohort. Moreover, down-regulation of JARID2 dramatically inhibited HCC cell migration, invasion, proliferation in vitro and metastasis in vivo, whereas overexpression of JARID2 significantly increased migration, invasion, proliferation in vitro and metastasis in vivo. Mechanistically, the data showed that JARID2 exerted its function by repressing PTEN expression through increasing H3K27 trimethylation (H3K27me3) at PTEN promoter region, which subsequently resulted in activation of protein kinase B (AKT) and enhanced epithelial mesenchymal transition (EMT). In conclusion, this study revealed that JARID2 promotes invasion and metastasis of HCC by facilitating EMT through PTEN/AKT signaling. PMID- 27259237 TI - In-depth mapping of the mouse brain N-glycoproteome reveals widespread N glycosylation of diverse brain proteins. AB - N-glycosylation is one of the most prominent and abundant posttranslational modifications of proteins. It is estimated that over 50% of mammalian proteins undergo glycosylation. However, the analysis of N-glycoproteins has been limited by the available analytical technology. In this study, we comprehensively mapped the N-glycosylation sites in the mouse brain proteome by combining complementary methods, which included seven protease treatments, four enrichment techniques and two fractionation strategies. Altogether, 13492 N-glycopeptides containing 8386 N glycosylation sites on 3982 proteins were identified. After evaluating the performance of the above methods, we proposed a simple and efficient workflow for large-scale N-glycosylation site mapping. The optimized workflow yielded 80% of the initially identified N-glycosylation sites with considerably less effort. Analysis of the identified N-glycoproteins revealed that many of the mouse brain proteins are N-glycosylated, including those proteins in critical pathways for nervous system development and neurological disease. Additionally, several important biomarkers of various diseases were found to be N-glycosylated. These data confirm that N-glycosylation is important in both physiological and pathological processes in the brain, and provide useful details about numerous N glycosylation sites in brain proteins. PMID- 27259238 TI - miRNA-337-3p inhibits gastric cancer progression through repressing myeloid zinc finger 1-facilitated expression of matrix metalloproteinase 14. AB - Matrix metalloproteinase 14 (MMP-14), a membrane-anchored MMP that promotes the tumorigenesis and aggressiveness, is highly expressed in gastric cancer. However, the transcriptional regulators of MMP-14 expression in gastric cancer still remain largely unknown. In this study, through mining computational algorithm programs and chromatin immunoprecipitation datasets, we identified adjacent binding sites of myeloid zinc finger 1 (MZF1) and miRNA-337-3p (miR-337-3p) within the MMP-14 promoter. We demonstrated that MZF1 directly bound to the MMP 14 promoter to facilitate its nascent transcription and expression in gastric cancer cell lines. In contrast, endogenous miR-337-3p suppressed the MMP-14 expression through recognizing its binding site within MMP-14 promoter. Mechanistically, miR-337-3p repressed the binding of MZF1 to MMP-14 promoter via recruiting Argonaute 2 and inducing repressive chromatin remodeling. Gain- and loss-of-function studies demonstrated that miR-337-3p suppressed the growth, invasion, metastasis, and angiogenesis of gastric cancer cells in vitro and in vivo through repressing MZF1-facilitated MMP-14 expression. In clinical specimens and cell lines of gastric cancer, MZF1 was highly expressed and positively correlated with MMP-14 expression. Meanwhile, miR-337-3p was under-expressed and inversely correlated with MMP-14 levels. miR-337-3p was an independent prognostic factor for favorable outcome of gastric cancer, and patients with high MZF1 or MMP-14 expression had lower survival probability. Taken together, these data indicate that miR-337-3p directly binds to the MMP-14 promoter to repress MZF1 facilitatd MMP-14 expression, thus suppressing the progression of gastric cancer. PMID- 27259240 TI - Interaction of DNA demethylase and histone methyltransferase upregulates Nrf2 in 5-fluorouracil-resistant colon cancer cells. AB - We recently reported that DNA demethylase ten-eleven translocation 1 (TET1) upregulates nuclear factor erythroid 2-related factor 2 (Nrf2) in 5-fluorouracil resistant colon cancer cells (SNUC5/5-FUR). In the present study, we examined the effect of histone modifications on Nrf2 transcriptional activation. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) were respectively decreased and increased in SNUC5/5-FUR cells as compared to non-resistant parent cells. Mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, while G9a was downregulated, leading to decreased dimethylation of histone H3 lysine 9. siRNA-mediated MLL knockdown decreased levels of Nrf2 and HO-1 to a greater extent than did silencing HAT1. Host cell factor 1 (HCF1) was upregulated in SNUC5/5-FUR cells, and we observed interaction between HCF1 and MLL. Upregulation of O-GlcNAc transferase (OGT), an activator of HCF1, was also associated with HCF1-MLL interaction. In SNUC5/5-FUR cells, a larger fraction of OGT was bound to TET1, which recruits OGT to the Nrf2 promoter region, than in SNUC5 cells. These findings indicate that SNUC5/5-FUR cells are under oxidative stress, which induces expression of histone methylation-related proteins as well as DNA demethylase, leading to upregulation of Nrf2 and 5-FU resistance. PMID- 27259239 TI - Candidate genes and pathways downstream of PAX8 involved in ovarian high-grade serous carcinoma. AB - Understanding the biology and molecular pathogenesis of ovarian epithelial cancer (EOC) is key to developing improved diagnostic and prognostic indicators and effective therapies. Although research has traditionally focused on the hypothesis that high-grade serous carcinoma (HGSC) arises from the ovarian surface epithelium (OSE), recent studies suggest that additional sites of origin exist and a substantial proportion of cases may arise from precursor lesions located in the Fallopian tubal epithelium (FTE). In FTE cells, the transcription factor PAX8 is a marker of the secretory cell lineage and its expression is retained in 96% of EOC. We have recently reported that PAX8 is involved in the tumorigenic phenotype of ovarian cancer cells. In this study, to uncover genes and pathways downstream of PAX8 involved in ovarian carcinoma we have determined the molecular profiles of ovarian cancer cells and in parallel of Fallopian tube epithelial cells by means of a silencing approach followed by an RNA-seq analysis. Interestingly, we highlighted the involvement of pathways like WNT signaling, epithelial-mesenchymal transition, p53 and apoptosis. We believe that our analysis has led to the identification of candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinoma. PMID- 27259241 TI - Comparative evaluation of three proliferation markers, Ki-67, TOP2A, and RacGAP1, in bronchopulmonary neuroendocrine neoplasms: Issues and prospects. AB - The classification of bronchopulmonary neuroendocrine neoplasms (BP-NEN) into four tumor entities (typical carcinoids (TC), atypical carcinoids (AC), small cell lung cancers (SCLC), large cell neuroendocrine lung carcinomas (LCNEC)) is difficult to perform accurately, but important for prognostic statements and therapeutic management decisions. In this regard, we compared the expression of three proliferation markers, Ki-67, Topoisomerase II alpha (TOP2A), and RacGAP1, in a series of tumor samples from 104 BP-NEN patients (24 TC, 21 AC, 52 SCLC, 7 LCNEC) using different evaluation methods (immunohistochemistry (IHC): Average evaluation, Hotspot evaluation, digital image analysis; RT-qPCR).The results indicated that all three markers had increased protein and mRNA expression with poorer differentiation and correlated well with each other, as well as with grading, staging, and poor survival. Compared with Ki-67 and TOP2A, RacGAP1 allowed for a clearer prognostic statement. The cut-off limits obtained for Ki-67 Average (IHC) were TC-AC 1.5, AC-SCLC 19, and AC-LCNEC 23.5. The Hotspot evaluation generated equal to higher, the digital image analysis generally lower between-entity cut-off limits.All three markers enabled a clear-cut differentiation between the BP-NEN entities, and all methods evaluated were suitable for marker assessment. However, to define optimal cut-off limits, the Ki 67 evaluation methods should be standardized. RacGAP1 appeared to be a new marker with great potential. PMID- 27259242 TI - Setup uncertainties for inter-fractional head and neck cancer in radiotherapy. AB - PURPOSE: The aim of this study is to determine the inter-fractional motion of cervical spine in radiotherapy (RT). MATERIALS AND METHODS: Eleven localized head and neck cancer patients who were treated from April 2014 to September 2015 were evaluated. Every patient underwent 3 times of computed tomography (CT) simulation with equivalent setting. Left-right (LR, x) and antero-posterior (AP, z) directional shift of cervical spine were evaluated using 33 number of CT image. In regard to random error, geometric changes were evaluated by 22 data set (compared the first obtained CT to second or third CT) by one-sample T test. Systemic error was evaluated by each patients' data set (11 pairs) by paired T test. RESULTS: The mean random error of LR and AP translational shift of cervical spine were -0.39 +/- 3.24 mm and -0.57 +/- 0.99 mm respectively. The mean random error of translational change of AP direction showed statistical significance (p = 0.014). The mean random error of x and z rotational shift were -0.07 +/- 0.29 degrees and -0.05 +/- 0.35 degrees , respectively. The mean systemic error of translational shift of LR and AP direction were -0.64 +/- 2.57 mm and -0.33 +/- 1.22 mm, respectively. The mean systemic error of rotational shift of x and z were 0.01 +/- 0.18 degrees and -0.27 +/- 0.33 degrees , respectively. The mean systemic error of rotational changes of z direction showed statistical difference (p = 0.022). CONCLUSIONS: We have to be aware of the inter-fractional motion of cervical spine in head and neck RT and give enough margins in RT planning. PMID- 27259243 TI - Estrogen receptor alpha inhibits senescence-like phenotype and facilitates transformation induced by oncogenic ras in human mammary epithelial cells. AB - Exposure to estrogen has long been associated with an increased risk of developing breast cancer. However, how estrogen signaling promotes breast carcinogenesis remains elusive. Senescence is known as an important protective response to oncogenic events. We aimed to elucidate the role of estrogen receptor alpha (ERalpha) on senescence in transformed human mammary epithelial cells and breast cancer cells. Our results show that ectopic expression of oncoprotein H ras-V12 in immortalized human mammary epithelial cells (HMEC) significantly inhibited the phosphorylation of the retinoblastoma protein (Rb) and increased the activity of the senescence-associated beta-galactosidase (SA-beta-Gal). These senescence-like phenotypes were reversed by ectopic expression of ERalpha. Similar inhibition of the H-ras-V12-induced SA-beta-Gal activity by ERalpha was also observed in the human mammary epithelial MCF-10A cells. Co-expression of ERalpha and H-ras-V12 resulted in HMEC anchorage-independent growth in vitro and tumor formation in vivo. Furthermore, inhibition of ERalpha expression induced senescence-like phenotypes in ERalpha positive human breast cancer cells such as increased activity of SA-beta-Gal, decreased phosphorylation of RB, and loss of mitogenic activity. Thus, the suppression of cellular senescence induced by oncogenic signals may be a major mechanism by which ERalpha promotes breast carcinogenesis. PMID- 27259244 TI - Careful neuropsychological testing reveals a novel genetic marker, GSTO1*C, linked to the pre-stage of Alzheimer's disease. AB - Approximately 30 million people currently suffer from late-onset Alzheimer's disease (LOAD) worldwide. Twin studies demonstrated that 60 to 80% of LOAD is genetically determined, 20% of which remaining unassigned. This case-control study included 118 cognitively healthy controls, 52 patients with mild cognitive impairment (MCI; the pre-stage of LOAD) and 71 LOAD patients. The participants were genotyped for the genetic LOAD marker apolipoprotein E4 (APOE4) and the single-nucleotide polymorphism rs4925 in glutathione S-transferase omega-1 (GSTO1). Additive logistic regression showed a novel, statistically significant association of the major allele GSTO1*C with MCI (OR1.9; p = 0.032). However, identification of significant SNP-disease relations required well-defined study groups. When classifying participants solely by the short Mini Mental State examination (MMSE), the associations of GSTO1*C and the reference marker APOE4 with MCI were cancelled. Moreover, even identifying only the control group by MMSE nullified a statistically significant association (OR1.8; p = 0.045) between GSTO1*C and LOAD. In contrast, these statistical relations were retained when the detailed Consortium to Establish a Registry for Alzheimer's Disease (CERAD-Plus) test battery was used. Hence, besides proposing rs4925 as a genetic marker for cognitive impairment, this work also emphasized the importance of carefully characterized controls in addition to well-diagnosed patients in case-control studies. PMID- 27259246 TI - The impact of 177Lu-octreotide therapy on 99mTc-MAG3 clearance is not predictive for late nephropathy. AB - Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of 99mTc-mercaptoacetyltriglycine (99mTc--MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6+/-0.4 GBq 177Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 +/- 53 ml/min/1.73 m2 before PRRT (baseline) and 221 +/- 45 ml/min/1.73 m2 after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by 99mTc-MAG3-clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy. PMID- 27259245 TI - A novel HSP90 inhibitor with reduced hepatotoxicity synergizes with radiotherapy to induce apoptosis, abrogate clonogenic survival, and improve tumor control in models of colorectal cancer. AB - The chaperone heat shock protein 90 (HSP90) crucially supports the maturation, folding, and stability of a variety of client proteins which are of pivotal importance for the survival and proliferation of cancer cells. Consequently, targeting of HSP90 has emerged as an attractive strategy of anti-cancer therapy, and it appears to be particularly effective in the context of molecular sensitization towards radiotherapy as has been proven in preclinical models of different cancer entities. However, so far the clinical translation has largely been hampered by suboptimal pharmacological properties and serious hepatotoxicity of first- and second-generation HSP90 inhibitors. Here, we report on NW457, a novel radicicol-derived member of the pochoxime family with reduced hepatotoxicity, how it inhibits the DNA damage response and how it synergizes with ionizing irradiation to induce apoptosis, abrogate clonogenic survival, and improve tumor control in models of colorectal cancer in vitro and in vivo. PMID- 27259248 TI - Study of single nucleotide polymorphisms of FBW7 and its substrate genes revealed a predictive factor for paclitaxel plus cisplatin chemotherapy in Chinese patients with advanced esophageal squamous cell carcinoma. AB - Paclitaxel plays a major role in the treatment of advanced esophageal squamous cell carcinoma. However, there is no biomarker that could be used to predict the clinical response of paclitaxel. This work was conducted to investigate the association of genetic polymorphisms in FBW7 and its substrate genes and the clinical response of paclitaxel. Patients with advanced esophageal squamous cell carcinoma were treated with paclitaxel 175 mg/m2 over 3 hours day 1 and cisplatin 75 mg/m2 day 1, every 3 weeks. The genotypes of 11 FBW7 and its substrate gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis revealed that patients with mTOR rs1057079 AG (ORadjusted: 4.59; 95% CI: 1.78-11.86) genotype had significant correlation with the clinical response of paclitaxel when compared with AA genotype after adjustment for sex, age, and chemotherapy cycle. The median progression-free survival (PFS) of patients with advanced ESCC who received paclitaxel plus cisplatin (TP) as first-line treatment is 14.3 months (95% CI: 9.0-19.60 months). The median PFS (mPFS) of AG genotypes and AA genotypes in mTOR rs1057079 were 17.31 months (95% CI: 15.9-18.67 months) and 9.8 months (95% CI: 8.58-11.02 months) (p=0.019), respectively. PMID- 27259247 TI - Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease. AB - Stress has been implicated as a risk factor for the severity and progression of sporadic Alzheimer's disease (AD). Early life experiences determine stress responsivity in later life, and modulate age-dependent cognitive decline. Therefore, we examined whether early life experiences influence AD outcome in a bigenic mouse model which progressively develops combined tau and amyloid pathology (biAT mice).Mice were subjected to either early life stress (ELS) or to 'positive' early handling (EH) postnatally (from day 2 to 9). In biAT mice, ELS significantly compromised long term survival, in contrast to EH which increased life expectancy. In 4 month old mice, ELS-reared biAT mice displayed increased hippocampal Abeta levels, while these levels were reduced in EH-reared biAT mice. No effects of ELS or EH were observed on the brain levels of APP, protein tau, or PSD-95. Dendritic morphology was moderately affected after ELS and EH in the amygdala and medial prefrontal cortex, while object recognition memory and open field performance were not affected. We conclude that despite the strong transgenic background, early life experiences significantly modulate the life expectancy of biAT mice. Parallel changes in hippocampal Abeta levels were evident, without affecting cognition of young adult biAT mice. PMID- 27259250 TI - Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO. AB - This study aimed to investigate the role of long noncoding RNAs (lncRNAs) in the metastasis of colorectal cancer (CRC). Metastasis is an important prognostic factor of CRC, and lncRNAs have been implicated in tumor proliferation and metastasis. The human CRC cell lines HCT116, HT29, SW480, DLD-1, and SW620 were used in the study. Genome-wide lncRNA expression patterns in metastatic lymph nodes compared with paired normal lymph nodes of CRC were assessed by microarray analysis. Gastric adenocarcinoma predictive long intergenic noncoding (GAPLINC) RNA was detected via functional prediction. The increased expression of GAPLINC was found to be positively correlated with larger tumor size, advanced tumor stage (T stage), advanced node stage (N stage), increased death, and shorter survival of patients with CRC by in situ hybridization analysis. Besides, the decreased expression of GAPLINC could significantly repress CRC cell invasion in vitro and also inhibit proliferation in vitro and in vivo. RNA pull-down with mass spectrum experiments revealed that PTB-associated splicing factor (PSF) and non-POU-domain-containing octamer-binding (NONO) protein bound to GAPLINC and reversed the effect of GAPLINC on cell invasion. Gene array and bioinformatics analyses identified that snail family zinc finger 2 (SNAI2) was involved in the biological processes of GAPLINC/PSF/NONO. This study indicated the importance of GAPLINC in promoting CRC invasion via binding to PSF/NONO and partly by stimulating the expression of SNAI2. Hence, GAPLINC may serve as a promising target for CRC diagnosis and therapy. The findings may help in developing a novel therapeutic strategy for patients with CRC. PMID- 27259249 TI - Extracellular matrix-specific Caveolin-1 phosphorylation on tyrosine 14 is linked to augmented melanoma metastasis but not tumorigenesis. AB - Caveolin-1 (CAV1) is a scaffolding protein that plays a dual role in cancer. In advanced stages of this disease, CAV1 expression in tumor cells is associated with enhanced metastatic potential, while, at earlier stages, CAV1 functions as a tumor suppressor. We recently implicated CAV1 phosphorylation on tyrosine 14 (Y14) in CAV1-enhanced cell migration. However, the contribution of this modification to the dual role of CAV1 in cancer remained unexplored. Here, we used in vitro [2D and transendothelial cell migration (TEM), invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question in B16F10 murine melanoma cells. CAV1 promoted directional migration on fibronectin or laminin, two abundant lung extracellular matrix (ECM) components, which correlated with enhanced Y14 phosphorylation during spreading. Moreover, CAV1-driven migration, invasion, TEM and metastasis were ablated by expression of the phosphorylation null CAV1(Y14F), but not the phosphorylation mimicking CAV1(Y14E) mutation. Finally, CAV1-enhanced focal adhesion dynamics and surface expression of beta1 integrin were required for CAV1-driven TEM. Importantly, CAV1 function as a tumor suppressor in tumor formation assays was not altered by the Y14F mutation. In conclusion, our results provide critical insight to the mechanisms of CAV1 action during cancer development. Specific ECM integrin interactions and Y14 phosphorylation are required for CAV1-enhanced melanoma cell migration, invasion and metastasis to the lung. Because Y14F mutation diminishes metastasis without inhibiting the tumor suppressor function of CAV1, Y14 phosphorylation emerges as an attractive therapeutic target to prevent metastasis without altering beneficial traits of CAV1. PMID- 27259251 TI - The isopeptidase inhibitor 2cPE triggers proteotoxic stress and ATM activation in chronic lymphocytic leukemia cells. AB - Relapse after treatment is a common and unresolved problem for patients suffering of the B-cell chronic lymphocytic leukemia (B-CLL). Here we investigated the ability of the isopeptidase inhibitor 2cPE to trigger apoptosis in leukemia cells in comparison with bortezomib, another inhibitor of the ubiquitin-proteasome system (UPS). Both inhibitors trigger apoptosis in CLL B cells and gene expression profiles studies denoted how a substantial part of genes up-regulated by these compounds are elements of adaptive responses, aimed to sustain cell survival. 2cPE treatment elicits the up-regulation of chaperones, proteasomal subunits and elements of the anti-oxidant response. Selective inhibition of these responses augments apoptosis in response to 2cPE treatment. We have also observed that the product of the ataxia telangiectasia mutated gene (ATM) is activated in 2cPE treated cells. Stimulation of ATM signaling is possibly dependent on the alteration of the redox homeostasis. Importantly ATM inhibition, mutations or down-modulation increase cell death in response to 2cPE. Overall this work suggests that 2cPE could offer new opportunities for the treatment of B-CLL. PMID- 27259252 TI - Virus-stimulated neutrophils in the tumor microenvironment enhance T cell mediated anti-tumor immunity. AB - The tumor microenvironment (TME) fosters tumors by attenuating anti-tumor immunity, reinforcing tumor cell survival and increasing angiogenesis. Among the constituents of the TME, here, we focused on tumor-associated neutrophils (TANs). First, we found that the combination of poly I:C and inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) synergistically suppressed tumor growth in the B16-F10 melanoma mouse model. In this model, poly I:C contributed to the recruitment of CD11b+Ly6G+ neutrophils to the TME, and co injection of poly I:C and HVJ-E increased CD11b+Ly6G+FAS+ TAN in the TME. Depletion of neutrophils abolished the synergistic anti-tumor effect of HVJ-E and poly I:C in B16-F10 tumors. We revealed that C-X-C motif chemokine ligand 2 (CXCL2) is produced in the TME by poly I:C, but HVJ-E enhanced neutrophil infiltration of the TME does not occur. An anti-CXCL2 antibody inhibited the tumor suppression by HVJ-E+poly I:C. HVJ-E in combination with recombinant CXCL2 protein or CXCL2 pDNA suppressed mouse melanoma by increasing cytotoxic T lymphocyte activity against B16-F10 melanoma, which was abolished by an anti-Ly6G antibody. HVJ-E directly and indirectly increased FAS and ICAM-1 expression in cultured bone marrow-derived naive neutrophils. Thus, HVJ-E activates anti-tumor immunity via anti-tumorigenic neutrophils in the TME. An HVJ-E vector containing the CXCL2 gene may be applicable as a novel cancer gene therapy strategy. PMID- 27259253 TI - HMGA2 sustains self-renewal and invasiveness of glioma-initiating cells. AB - Glioblastoma multiforme (GBM) is the most common type of brain tumors with dismal outcomes. The mesenchymal phenotype is the hallmark of tumor aggressiveness in GBMs. Perivascular smooth muscle cells (pericytes) are essential in homeostasis of normal and glioma tissues. Here we found HMGA2, an architectural transcription factor that promotes mesenchymal phenotypes in a number of solid tumors, is highly expressed in mesenchymal subtype of GBMs and labels both glioma pericytes and glioma-initiating cells (GICs). Accordingly, depletion of HMGA2 in GICs resulted in compromised self-renewal and tumorigenic capability, as well as undermined mesenchymal or pericyte differentiation. We further showed HMGA2 allows expressions of FOXM1 and PLAU to maintain GIC propagation, gliomagenesis and aggressiveness both in vitro and in vivo. Therefore, suppressing HMGA2 mediated GIC self-renewal and invasiveness might be a promising means to treat GBMs. PMID- 27259254 TI - Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation. AB - While transformation of normal cells to cancer cells is accompanied with a switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis, it is interesting to ask if cancer cells can revert from Warburg effect to OXPHOS. Our previous works suggested that cancer cells reverted to OXPHOS, when they were exposed to lactic acidosis, a common factor in tumor environment. However, the conclusion cannot be drawn unless ATP output from glycolysis and OXPHOS is quantitatively determined. Here we quantitatively measured ATP generation from glycolysis and OXPHOS in 9 randomly selected cancer cell lines. Without lactic acidosis, glycolysis and OXPHOS generated 23.7% - 52.2 % and 47.8% - 76.3% of total ATP, respectively; with lactic acidosis (20 mM lactate with pH 6.7), glycolysis and OXPHOS provided 5.7% - 13.4% and 86.6% - 94.3% of total ATP. We concluded that cancer cells under lactic acidosis reverted from Warburg effect to OXPHOS phenotype. PMID- 27259255 TI - High expression of galectin-7 associates with poor overall survival in patients with non-metastatic clear-cell renal cell carcinoma. AB - BACKGROUND: Galectin-7, has a controversial role in tumor progression, can either suppress tumor growth or induce chemoresistance depends on different tumor histology types. The aim was to appraise Galectin-7 expression on the overall survival (OS) of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) following surgery. RESULTS: High galectin-7 expression was specifically correlated with necrosis (P = 0.015). Multivariate analysis confirmed galectin-7 as an independent prognosticator for OS (P = 0.005). High galectin-7 expression suggested poor OS (P < 0.001), particularly with UISS intermediate and high score groups. Notably, the predictive accuracy of the traditional prognostic scores was improved when combined with galectin-7 expression. MATERIALS AND METHODS: We retrospectively enrolled 416 patients who underwent nephrectomy at a single institute between 2008 and 2009 and detected their intratumor galectin-7 expression by immunohistochemistry. Kaplan-Meier method was conducted to plot survival curves and multivariate cox regression analysis for potential independent prognostic factors on OS. A nomogram was constructed with concordance index (C-index) and Akaike's Information Criteria (AIC) to appraise prognostic accuracy of different models. CONCLUSIONS: High galectin-7 expression is an independent adverse predictor for survival. Evaluation of galectin-7 could help guide postsurgical management for non-metastatic ccRCC patients. PMID- 27259257 TI - Ubiquitin specific peptidase 21 regulates interleukin-8 expression, stem-cell like property of human renal cell carcinoma. AB - USP family proteins play essential roles in cancer cell proliferation and apoptosis and represent as candidate targets for cancer therapeutics. However, the effects and underlying mechanism of USP21 on renal cell carcinomas (RCC) remain unclear. In the present study, we investigate the effects of USP21 on proliferation, invasion and cancer stem cells (CSCs) property of RCC cell lines. As a result, siRNA-mediated depletion of USP21 inhibits cell proliferation, invasion ability and decreases the CSCs percentage of RCC cell lines. Complementarily, forced expression of USP21 leads to increase of tumorigenic properties. In addition, CSCs properties assessed by sphere formation assays demonstrated that depletion of USP21 impair the self-renewal capability of CSCs. Furthermore, decrease USP21 levels is associated with repression of interleukin 8 (IL-8), a chemokine that regulates CSCs characteristics in RCC. Mechanistically, USP21 binds to the promoter region of IL-8 and mediates transcriptional initiation. These data suggest that USP21/IL-8 could be a pair of the critical molecular targets for the development of therapeutic strategies for RCC. PMID- 27259258 TI - Multi-kinase inhibitors interact with sildenafil and ERBB1/2/4 inhibitors to kill tumor cells in vitro and in vivo. AB - We have recently demonstrated that multi-kinase inhibitors such as sorafenib and pazopanib can suppress the detection of chaperones by in situ immuno fluorescence, which is further enhanced by phosphodiesterase 5 inhibitors. Sorafenib and pazopanib inhibited the HSP90 ATPase activity with IC50 values of ~1.0 MUM and ~75 nM, respectively. Pazopanib docked in silico with two possible poses into the HSP90 ATP binding pocket. Pazopanib and sildenafil combined to reduce the total protein levels of HSP1H/p105 and c-MYC and to reduce their co localization. Sorafenib/pazopanib combined with sildenafil in a [GRP78+HSP27] dependent fashion to: (i) profoundly activate an eIF2alpha/Beclin1 pathway; (ii) profoundly inactivate mTOR and increase ATG13 phosphorylation, collectively resulting in the formation of toxic autophagosomes. In a fresh PDX isolate of NSCLC combined knock down of [ERBB1+ERBB3] or use of the ERBB1/2/4 inhibitor afatinib altered cell morphology, enhanced ATG13 phosphorylation, inactivated NFkappaB, and further enhanced [sorafenib/pazopanib + sildenafil] lethality. Identical data to that with afatinib were obtained knocking down PI3K p110alpha/beta or using buparlisib, copanlisib or the specific p110alpha inhibitor BYL719. Afatinib adapted NSCLC clones were resistant to buparlisib or copanlisib but were more sensitive than control clones to [sorafenib + sildenafil] or [pazopanib + sildenafil]. Lapatinib significantly enhanced the anti-tumor effect of [regorafenib + sildenafil] in vivo; afatinib and BYL719 enhanced the anti-tumor effects of [sorafenib + sildenafil] and [pazopanib] in vivo, respectively. PMID- 27259259 TI - Quantitative in vivo optical tomography of cancer progression & vasculature development in adult zebrafish. AB - We describe a novel approach to study tumour progression and vasculature development in vivo via global 3-D fluorescence imaging of live non-pigmented adult zebrafish utilising angularly multiplexed optical projection tomography with compressive sensing (CS-OPT). This "mesoscopic" imaging method bridges a gap between established ~MUm resolution 3-D fluorescence microscopy techniques and ~mm-resolved whole body planar imaging and diffuse tomography. Implementing angular multiplexing with CS-OPT, we demonstrate the in vivo global imaging of an inducible fluorescently labelled genetic model of liver cancer in adult non pigmented zebrafish that also present fluorescently labelled vasculature. In this disease model, addition of a chemical inducer (doxycycline) drives expression of eGFP tagged oncogenic K-RASV12 in the liver of immune competent animals. We show that our novel in vivo global imaging methodology enables non-invasive quantitative imaging of the development of tumour and vasculature throughout the progression of the disease, which we have validated against established methods of pathology including immunohistochemistry. We have also demonstrated its potential for longitudinal imaging through a study of vascular development in the same zebrafish from early embryo to adulthood. We believe that this instrument, together with its associated analysis and data management tools, constitute a new platform for in vivo cancer studies and drug discovery in zebrafish disease models. PMID- 27259260 TI - ATM protein is deficient in over 40% of lung adenocarcinomas. AB - Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM deficient lung adenocarcinoma every year. PMID- 27259261 TI - CDH1 rs9929218 variant at 16q22.1 contributes to colorectal cancer susceptibility. AB - Colorectal cancer (CRC) is the third most common cancer. Large-scale genome-wide association studies (GWAS) have been performed and reported some novel CRC susceptibility variants in European ancestry including the CDH1 rs9929218. Following GWAS and candidate studies evaluated the association between the CDH1 rs9929218 polymorphism and CRC in European, Asian and American populations. However, these studies reported inconsistent associations. Evidence shows that rs9929218 may regulate different gene expressions in different human tissues. Here, we reevaluated this association using large-scale samples from 16 studies (n=131768) using a meta-analysis method. In heterogeneity test, we did not identify significant heterogeneity among these studies. Meta-analysis using fixed effect model showed significant association between rs9929218 and CRC (P=6.16E 21, odds ratio (OR) =0.92, 95% confidence interval (CI) 0.91-0.94). In order to validate the effect of rs9929218 variant on CDH1 expression, we further performed a functional analysis using two large-scale expression datasets. We identified significant regulation relation between rs9929218 variant and the expression of CDH1, ZFP90, RP11-354M1.2 and MCOLN2 by both cis-effect and trans-effect. In summary, our analysis highlights significant association between rs9929218 polymorphism and CRC susceptibility. PMID- 27259262 TI - MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling. AB - Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion of MDA-MB-231LN cells, and AF1q up-regulated platelet-derived growth factor receptor (PDGFR) signaling. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Src kinase inhibitor PP1. Moreover, AF1q up-regulated tyrosine kinase signaling through PDGFR signaling, which was blockable by imatinib. In conclusion, we demonstrated that enhanced AF1q expression contributes to persistent and oncogenic pYSTAT3 levels in invasive carcinoma cells by activating Src kinase through activation of the PDGF-B/PDGFR cascade. Therefore, AF1q plays an essential role as a cofactor in PDGF-B-driven STAT3 signaling. PMID- 27259264 TI - EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1alpha signaling. AB - Cancer cells prefer glycolysis for energy metabolism, even when there is sufficient oxygen to make it unnecessary. This is called the Warburg effect, and it promotes tumorigenesis and malignant progression. In this study, we demonstrated that EZH2, a multifaceted oncogenic protein involved in tumor proliferation, invasion and metastasis, promotes glioblastoma tumorigenesis and malignant progression through activation of the Warburg effect. We observed that HIF1alpha is a target of EZH2 whose activation is necessary for EZH2-mediated metabolic adaption, and that HIF1alpha is activated upon EZH2 overexpression. EZH2 suppressed expression of EAF2, which in turn upregulated HIF1alpha levels. We conclude from these results that EZH2 promotes tumorigenesis and malignant progression in part by activating glycolysis through an EAF2-HIF1alpha signaling axis. PMID- 27259265 TI - Demonstration of potential link between Helicobacter pylori related promoter CpG island methylation and telomere shortening in human gastric mucosa. AB - BACKGROUND: Telomere length shortening in Helicobacter pylori (H. pylori) infected gastric mucosa constitutes the earliest steps toward neoplastic transformation. In addition to this genotoxic changes, epigenetic changes such as promoter CpG island (PCGI) methylation are frequently occurred in H. pylori infected gastric mucosa. The aim of this study was to investigate a potential link between H. pylori related PCGI methylation and telomere length shortening in the human gastric mucosa. METHODS: Telomere length was measured in non-neoplastic gastric mucosa from 106 cancer-free subjects. To identify H. pylori related PCGI methylation, bisulfite pyrosequencing was used to quantify the methylation of 49 PCGIs from 47 genes and LINE1 repetitive elementResults: We identified five PCGIs (IGF2, SLC16A12, SOX11, P2RX7 and MYOD1), which the methylation is closely associated with H. pylori infection. Hypermethylation of all these PCGIs was associated with development of pathological state from normal to mild, active, and atrophic gastritis (P<0.001) and lower pepsinogen I/II ratio (P<0.05), an indicator for gastric mucosal atrophy. Telomere shortening was significantly associated with mean Z score methylation of five PCGIs (R=-0.39, P<0.0001) and four of these locus (IGF2: R=-0.35, P=0.0003, SLC16A12: R=-0.35, P=0.0002, P2RX7: R=-0.29, P=0.003, and MYOD1: R=-0.33, P=0.0005). Multivariate analysis revealed that telomere shortening held an increased risk for hypermethylation (odds ratio: 1.71, 95% confidence interval: 1.11-2.63, P=0.016). CONCLUSION: Potential link between H. pylori related PCGI methylation and telomere shortening emphasize the importance of genotoxic-epigenetic interaction in the pathological state of H. pylori infected gastric mucosa. PMID- 27259267 TI - BET inhibition as a new strategy for the treatment of gastric cancer. AB - Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer. PMID- 27259268 TI - (-)-Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma. AB - We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment. PMID- 27259269 TI - Orai1 promotes tumor progression by enhancing cancer stemness via NFAT signaling in oral/oropharyngeal squamous cell carcinoma. AB - Emerging evidence indicates that Orai1, a key calcium channel for store-operated Ca2+ entry, is associated with human cancer. However, the underlying mechanism by which Orai1 regulates cancer progression remains unknown. Here we report that intracellular level of Orai1 is increased in a stepwise manner during oral/oropharyngeal carcinogenesis and highly expressed in cancer stem-like cell (CSC)-enriched populations of human oral/oropharyngeal squamous cell carcinoma (OSCC). Ectopic Orai1 expression converted non-tumorigenic immortalized oral epithelial cells to malignant cells that showed CSC properties, e.g., self renewal capacity, increased ALDH1HIGH cell population, increased key stemness transcription factors, and enhanced mobility. Conversely, inhibition of Orai1 suppressed tumorigenicity and CSC phenotype of OSCC, indicating that Orai1 could be an important element for tumorigenicity and stemness of OSCC. Mechanistically, Orai1 activates its major downstream effector molecule, NFATc3. Knockdown of NFATc3 in the Orai1-overexpressing oral epithelial cells abrogates the effect of Orai1 on CSC phenotype. Moreover, antagonist of NFAT signaling also decreases CSC phenotype, implying the functional importance of Orai1/NFAT axis in OSCC CSC regulation. Our study identifies Orai1 as a novel molecular determinant for OSCC progression by enhancing cancer stemness, suggesting that inhibition of Orai1 signaling may offer an effective therapeutic modality against OSCC. PMID- 27259272 TI - High dose and compartmental target volume may improve patient outcome after radiotherapy for pelvic bone metastases from hepatocellular carcinoma. AB - PURPOSE: Pelvic bone metastases are difficult to treat because of complex pelvic bone anatomy and the proximity of normal organs. The adequacy of radiation dose and field coverage was evaluated. PATIENTS AND METHODS: We analyzed 146 cases of pelvic bone metastases from HCC treated with radiotherapy (RT). Bone metastases were confirmed using CT/MRI. Subjective pain response was assessed using the visual analogue scale, and treatment-related toxicity with the Common Terminology Criteria for Adverse Events v3.0. Local failure free survival (LFFS) and overall survival were estimated using the Kaplan-Meier method. RESULTS: The local control rate was 80.1% and the pain control rate was 68.5%. Compartmental target volume (CTV), encompassing the whole compartment of the involved bone, was found to be a significant factor (1-year LFFS, 78% vs. 50%; p=0.001). Sites of metastasis were categorized as either upper or lower pelvic bone; both categories showed improved local control with CTV. Metastatic lesions that received more than 50 Gy of EQD2 showed more partial response in pain after RT (58% vs. 79%; p=0.007). No patient showed toxicity higher than Grade IV. CONCLUSION: Compartmental RT targeted to the involved bone was associated with improved local control and LFFS. High-dose radiation was associated with an improved treatment response. PMID- 27259271 TI - Identification of Glypican-3 as a potential metastasis suppressor gene in gastric cancer. AB - Gastric cancer is a prevalent tumor that is usually detected at an advanced metastatic stage. Currently, standard therapies are mostly ineffective. Here, we report that Glypican-3 (GPC3) is absent in invasive tumors and metastatic lymph nodes, in particular in aggressive and highly disseminated signet ring cell carcinomas. We demonstrate that loss of GPC3 correlates with poor overall survival in patients. Moreover, we show that absence of GPC3 causes up-regulation of MAPK/FoxM1 signaling and that blockade of this pathway alters cellular invasion. An inverse correlation between GPC3 and FoxM1 is also shown in patient samples. These data identify GPC3 as a potential metastasis suppressor gene and suggest its value as a prognostic marker in gastric cancer. Development of therapies targeting signaling downstream of GPC3 are warranted. PMID- 27259270 TI - BET bromodomain inhibitors suppress EWS-FLI1-dependent transcription and the IGF1 autocrine mechanism in Ewing sarcoma. AB - Ewing sarcoma is driven by characteristic chromosomal translocations between the EWSR1 gene with genes encoding ETS family transcription factors (EWS-ETS), most commonly FLI1. However, direct pharmacological inhibition of transcription factors like EWS-FLI1 remains largely unsuccessful. Active gene transcription requires orchestrated actions of many epigenetic regulators, such as the bromodomain and extra-terminal domain (BET) family proteins. Emerging BET bromodomain inhibitors have exhibited promising antineoplastic activities via suppression of oncogenic transcription factors in various cancers. We reasoned that EWS-FLI1-mediated transcription activation might be susceptible to BET inhibition. In this study, we demonstrated that small molecule BET bromodomain inhibitors repressed EWS-FLI1-driven gene signatures and downregulated important target genes. However, expression of EWS-FLI1 was not significantly affected. Repression of autocrine IGF1 by BET inhibitors led to significant inhibition of the IGF1R/AKT pathway critical to Ewing sarcoma cell proliferation and survival. Consistently, BET inhibitors impaired viability and clonogenic survival of Ewing sarcoma cell lines and blocked EWS-FLI1-induced transformation of mouse NIH3T3 fibroblast cells. Selective depletion of individual BET genes partially phenocopied the actions of BET inhibitors. Finally, the prototypical BET inhibitor, JQ1, significantly repressed Ewing sarcoma xenograft tumor growth. These findings suggest therapeutic potential of BET inhibitors in Ewing sarcoma and highlight an emerging paradigm of using epigenetic agents to treat cancers driven by fusion transcription factors. PMID- 27259273 TI - MDM2 knockdown mediated by a triazine-modified dendrimer in the treatment of non small cell lung cancer. AB - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the five-year survival rate is lower in advanced NSCLC patients. Chemotherapy is a widely used strategy in NSCLC treatment, but is usually limited by poor therapeutic efficacy and adverse effects. Therefore, a new therapeutic regimen is needed for NSCLC treatment. Gene therapy is a new strategy in the treatment of NSCLC. However, the lack of efficient and low toxic vectors remains the major obstacle. Here, we developed a biocompatible dendrimer as a non-viral vector for the delivery of mouse double minute2 (MDM2) siRNA in vitro and in vivo to treat NSCLC. The triazine-modified dendrimer efficiently stimulates the down-regulation of MDM2 gene in NSCLC PC9 cells, which induces significant cell apoptosis through the activation of apoptosis markers such as caspase-8 and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the dendrimer/MDM2 siRNA polyplexes showed excellent activity in the inhibition of tumor growth in a PC9 xenograft tumor model. These results suggested that inhibition the expression of MDM2 might be a potential target in NSCLC treatment. PMID- 27259274 TI - Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy. AB - The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate modified star-shaped copolymer (FA-CD-PLLD) consisting of beta-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP 9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored. PMID- 27259275 TI - MUC1-C induces DNA methyltransferase 1 and represses tumor suppressor genes in acute myeloid leukemia. AB - Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML); however, the regulation of DNA methyltransferase 1 (DNMT1), which is responsible for maintenance of DNA methylation patterns, has largely remained elusive. MUC1-C is a transmembrane oncoprotein that is aberrantly expressed in AML stem-like cells. The present studies demonstrate that targeting MUC1-C with silencing or a pharmacologic inhibitor GO-203 suppresses DNMT1 expression. In addition, MUC1 expression positively correlates with that of DNMT1 in primary AML cells, particularly the CD34+/CD38- population. The mechanistic basis for this relationship is supported by the demonstration that MUC1-C activates the NF kappaB p65 pathway, promotes occupancy of the MUC1-C/NF-kappaB complex on the DNMT1 promoter and drives DNMT1 transcription. We also show that targeting MUC1-C substantially reduces gene promoter-specific DNA methylation, and derepresses expression of tumor suppressor genes, including CDH1, PTEN and BRCA1. In support of these results, we demonstrate that combining GO-203 with the DNMT1 inhibitor decitabine is highly effective in reducing DNMT1 levels and decreasing AML cell survival. These findings indicate that (i) MUC1-C is an attractive target for the epigentic reprogramming of AML cells, and (ii) targeting MUC1-C in combination with decitabine is a potentially effective clinical approach for the treatment of AML. PMID- 27259276 TI - Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1/2 and p38 MAPKs. AB - Cachexia affects the majority of cancer patients, with currently no effective treatments. Cachexia is defined by increased fatigue and loss of muscle function resulting from muscle and fat depletion. Previous studies suggest that chemotherapy may contribute to cachexia, although the causes responsible for this association are not clear. The purpose of this study was to investigate the mechanism(s) associated with chemotherapy-related effects on body composition and muscle function. Normal mice were administered chemotherapy regimens used for the treatment of colorectal cancer, such as Folfox (5-FU, leucovorin, oxaliplatin) or Folfiri (5-FU, leucovorin, irinotecan) for 5 weeks. The animals that received chemotherapy exhibited concurrent loss of muscle mass and muscle weakness. Consistently with previous findings, muscle wasting was associated with up regulation of ERK1/2 and p38 MAPKs. No changes in ubiquitin-dependent proteolysis or in the expression of TGFbeta-family members were detected. Further, marked decreases in mitochondrial content, associated with abnormalities at the sarcomeric level and with increase in the number of glycolytic fibers were observed in the muscle of mice receiving chemotherapy. Finally, ACVR2B/Fc or PD98059 prevented Folfiri-associated ERK1/2 activation and myofiber atrophy in C2C12 cultures. Our findings demonstrate that chemotherapy promotes MAPK dependent muscle atrophy as well as mitochondrial depletion and alterations of the sarcomeric units. Therefore, these findings suggest that chemotherapy potentially plays a causative role in the occurrence of muscle loss and weakness. Moreover, the present observations provide a strong rationale for testing ACVR2B/Fc or MEK1 inhibitors in combination with anticancer drugs as novel strategies aimed at preventing chemotherapy-associated muscle atrophy. PMID- 27259277 TI - The transcription factor FOXN3 inhibits cell proliferation by downregulating E2F5 expression in hepatocellular carcinoma cells. AB - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and the mechanisms underlying the development of HCC remain to be elucidated. Forkhead box N3 (FOXN3) is an important member of the FOX family of transcription factors that plays an essential role in several cancers but has not been investigated in HCC. In this study, we demonstrate that FOXN3 is downregulated in human primary HCC tissues compared with their matched adjacent liver tissues. Functional tests of FOXN3 demonstrated that FOXN3 inhibits the proliferation of HCC cells in vitro and in vivo. Additionally, FOXN3 repressed the mRNA and protein expression of E2F5, a reported potential oncogene, by inhibiting the promoter activity of E2F5. Collectively, our findings indicate that FOXN3 functions as a tumor suppressor in HCC by downregulating the expression of E2F5. PMID- 27259281 TI - Erratum to: Fusion transcript loci share many genomic features with non-fusion loci. PMID- 27259278 TI - Extracellular vesicles secreted by highly metastatic clonal variants of osteosarcoma preferentially localize to the lungs and induce metastatic behaviour in poorly metastatic clones. AB - Osteosarcoma (OS) is the most common pediatric bone tumor and is associated with the emergence of pulmonary metastasis. Unfortunately, the mechanistic basis for metastasis remains unclear. Tumor-derived extracellular vesicles (EVs) have been shown to play critical roles in cell-to-cell communication and metastatic progression in other cancers, but their role in OS has not been explored. We show that EVs secreted by cells derived from a highly metastatic clonal variant of the KHOS cell line can be internalized by a poorly metastatic clonal variant of the same cell line and induce a migratory and invasive phenotype. This horizontal phenotypic transfer is unidirectional and provides evidence that metastatic potential may arise via interclonal co-operation. Proteomic analysis of the EVs secreted by highly metastatic OS clonal variants results in the identification of a number of proteins and G-protein coupled receptor signaling events as potential drivers of OS metastasis and novel therapeutic targets. Finally, multiphoton microscopy with fluorescence lifetime imaging in vivo, demonstrated a preferential seeding of lung tissue by EVs derived from highly metastatic OS clonal variants. Thus, we show that EVs derived from highly metastatic clonal variants of OS may drive metastatic behaviour via interclonal co-operation and preferential colonization of the lungs. PMID- 27259280 TI - The source of SYBR green master mix determines outcome of nucleic acid amplification reactions. AB - BACKGROUND: Quantitative (q) PCR by amplification of nucleic acid with a fluorescent dye is widely used. Selection of adequate PCR reagents and devices is relevant to achieve reliable and consistent data. Our main objective was to test the robustness of different commercial SYBR green PCR mixes with respect to specificity and sensitivity of the PCR assay, across various PCR machines (Light Cycler 96, ViiA7) and amplification protocols. Herein, we applied PCR protocols for determining mRNA transcript levels, DNA copy numbers, and DNA genotype. RESULTS: First, we set up 70 primer-based assays that targeted immune-related mRNA transcripts. Of the 70 assays 66 (94.3 %) resulted in a single melting curve peak, indicating specificity of the amplification, with PCR mixes from large vendors (Roche, ABI, Bio-Rad). But this was only seen when the PCR protocol that was indicated in the vendor's guidelines for each particular mix was applied. When deviating from the prescribed protocol, suboptimal melting curves were most often seen when using Roche SYBR green. With respect to PCR yields, the use of ABI mix more often led to lower Cq values. Second, we set up 20 primer-selective PCR assays to target different insertion-deletion and single nucleotide polymorphism regions throughout the genome. The variation in delta Cq between positive and negative DNA samples among the PCR assays was the lowest when using ABI master mix. Finally, the quality of high resolution melting (HRM) assays for DNA genotyping was compared between four commercial HRM PCR mixes (Roche, Bioline, PCR Biosystems, ABI). Only Roche and ABI mixes produced optimal clusters of melting profiles that clearly distinguished genotype variants. CONCLUSIONS: The current results show a preference for the use of ABI mix when it comes to obtaining higher sensitivity in cDNA analysis and a higher consistency among assays in distinguishing DNA genotypes among different individuals. For HRM assays, it is advisable to use master mix from a relatively large vendor. PMID- 27259282 TI - Maternal haemoglobin concentrations before and during pregnancy and stillbirth risk: a population-based case-control study. AB - BACKGROUND: Results of previous studies on the association between maternal haemoglobin concentration during pregnancy and stillbirth risk are inconclusive. It is not clear if haemoglobin concentration before pregnancy has a role. Using prospectively collected information from pre-pregnancy and antenatal visits, we investigated associations of maternal haemoglobin concentrations before and during pregnancy and haemoglobin dilution with stillbirth risk. METHODS: In a population-based case-control study from rural Golestan, a province in northern Iran, we identified 495 stillbirths (cases) and randomly selected 2,888 control live births among antenatal health-care visits between 2007 and 2009. Using logistic regression, we estimated associations of maternal haemoglobin concentrations, haemoglobin dilution at different stages of pregnancy, with stillbirth risk. RESULTS: Compared with normal maternal haemoglobin concentration (110-120 g/l) at the end of the second trimester, high maternal haemoglobin concentration (>=140 g/l) was associated with a more than two-fold increased stillbirth risk (OR = 2.31, 95 % CI [1.30-4.10]), while low maternal haemoglobin concentration (<110 g/l) was associated with a 37 % reduction in stillbirth risk. Haemoglobin concentration before pregnancy was not associated with stillbirth risk. Decreased haemoglobin concentration, as measured during pregnancy (OR = 0.61, 95 % CI [0.46, 0.80]), or only during the second trimester (OR = 0.75, 95 % CI [0.62, 0.90]), were associated with reduced stillbirth risk. The associations were essentially similar for preterm and term stillbirths. CONCLUSIONS: Haemoglobin concentration before pregnancy is not associated with stillbirth risk. High haemoglobin level and absence of haemoglobin dilution during pregnancy could be considered as indicators of a high-risk pregnancy. PMID- 27259283 TI - Ruptured aneurysms of the intradural artery of adamkiewicz: Angiographic features and treatment options. AB - We present an unusual case of a 59year old male patient who presented with acute, bilateral lower extremity weakness and was found to have non-traumatic spinal subarachnoid hemorrhage. Diagnostic workup including MRI and angiography revealed an aneurysm of the artery of Ademkiewicz. This was managed conservatively and the patient has had marked clinical improvement. We present the details of this unusual case as well as a literature review related to aneurysms of the artery of Ademkiewicz. PMID- 27259285 TI - Erratum to: Repression of chimeric transcripts emanating from endogenous retrotransposons by a sequence-specific transcription factor. PMID- 27259284 TI - Systematic review on the evaluation criteria of orphan medicines in Central and Eastern European countries. AB - BACKGROUND: In case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries. OBJECTIVES: To explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs. METHODS: A systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements. RESULTS: From the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions. CONCLUSIONS: The evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan drugs. The search found only a small number of studies coming from CEE, therefore European policies on orphan drugs may be based largely on experiences in WE countries. More research should be done in the future in CEE because financing high-priced orphan drugs involves a greater burden for these countries. PMID- 27259287 TI - Prevalence, causes and management outcome of intestinal obstruction in Adama Hospital, Ethiopia. AB - BACKGROUND: In Africa, acute intestinal obstruction accounts for a great proportion of morbidity and mortality. Ethiopia is one of the countries where intestinal obstruction is a major cause of morbidity and mortality. This study aims to determine prevalence, causes and management outcome of intestinal obstruction in Adama Hospital in Oromia region, Ethiopia. METHOD: A hospital based cross-sectional study design was used. Data covering the past three years were collected from hospital medical records of sampled patients. The collected data were checked for any inconsistency, coded and entered into SPSS version 16.0 for data processing and analysis. Descriptive and logistic regression analyses were used. Statistical significance was based on confidence interval (CI) of 95 % at a p-value of < 0.05. RESULT: 262 patients were admitted with intestinal obstruction. The prevalence of intestinal obstruction was 21.8 % and 4.8 % among patients admitted for acute abdomen surgery and total surgical admissions, respectively. The mortality rate was 2.5 % (6 of 262). The most common cause of small bowel obstruction was intussusceptions in 48 patients (30.9 %), followed by small bowel volvulus in 47 patients (30.3 %). Large bowel obstruction was caused by sigmoid volvulus in 60 patients (69.0 %) followed by colonic tumor in 12 patients (13.8 %). After controlling for possible confounding factors, the major predictors of management outcome of intestinal obstruction were: duration of illness before surgical intervention (adjusted odds ratio (AOR) = 0.49, 95 % CI: 0.25-0.97); intra-operative findings [Viable small bowel volvulus (SBV) (AOR = 0.08, 95 % CI: 0.01-0.95) and viable (AOR = 0.17, 95 % CI: 0.03-0.88)]; completion of intra-operative procedures (bowel resection & anastomosis (AOR = 3.05, 95 % CI: 1.04-8.94); and length of hospital stay (AOR = 0.05, 95 % CI: 0.01 0.16). CONCLUSION: Small bowel obstruction was more prevalent than large bowel obstruction. Intussusceptions and sigmoid volvulus were the leading causes of small and large bowel obstruction. Laparotomy was the most common methods of intestinal obstruction management. Bowel resection and anastomosis was the commonest intra-operative procedure done and is associated with postoperative complications. Wound infection in the affected area should be improved because it is the most common postoperative complication. This can be decreased by appropriate surgical technique and wound care with sterile techniques. PMID- 27259286 TI - Factors associated with high heterogeneity of malaria at fine spatial scale in the Western Kenyan highlands. AB - BACKGROUND: The East African highlands are fringe regions between stable and unstable malaria transmission. What factors contribute to the heterogeneity of malaria exposure on different spatial scales within larger foci has not been extensively studied. In a comprehensive, community-based cross-sectional survey an attempt was made to identify factors that drive the macro- and micro epidemiology of malaria in a fringe region using parasitological and serological outcomes. METHODS: A large cross-sectional survey including 17,503 individuals was conducted across all age groups in a 100 km(2) area in the Western Kenyan highlands of Rachuonyo South district. Households were geo-located and prevalence of malaria parasites and malaria-specific antibodies were determined by PCR and ELISA. Household and individual risk-factors were recorded. Geographical characteristics of the study area were digitally derived using high-resolution satellite images. RESULTS: Malaria antibody prevalence strongly related to altitude (1350-1600 m, p < 0.001). A strong negative association with increasing altitude and PCR parasite prevalence was found. Parasite carriage was detected at all altitudes and in all age groups; 93.2 % (2481/2663) of malaria infections were apparently asymptomatic. Malaria parasite prevalence was associated with age, bed net use, house construction features, altitude and topographical wetness index. Antibody prevalence was associated with all these factors and distance to the nearest water body. CONCLUSION: Altitude was a major driver of malaria transmission in this study area, even across narrow altitude bands. The large proportion of asymptomatic parasite carriers at all altitudes and the age dependent acquisition of malaria antibodies indicate stable malaria transmission; the strong correlation between current parasite carriage and serological markers of malaria exposure indicate temporal stability of spatially heterogeneous transmission. PMID- 27259288 TI - Concierge, Wellness, and Block Fee Models of Primary Care: Ethical and Regulatory Concerns at the Public-Private Boundary. AB - In bioethics and health policy, we often discuss the appropriate boundaries of public funding; how the interface of public and private purchasers and providers should be organized and regulated receives less attention. In this paper, I discuss ethical and regulatory issues raised at this interface by three medical practice models (concierge care, executive wellness clinics, and block fee charges) in which physicians provide insured services (whether publicly insured, privately insured, or privately insured by public mandate) while requiring or requesting that patients pay for services or for the non-insured services of the physicians themselves or their associates. This choice for such practice models is different from the decision to design an insurance plan to include or exclude user fees, co-payments and deductibles. I analyze the issues raised with regards to familiar health care values of equity and efficiency, while highlighting additional concerns about fair terms of access, provider integrity, and fair competition. I then analyze the common Canadian regulatory response to block fee models, considering their extension to wellness clinics, with regards to fiduciary standards governing the physician-patient relationship and the role of informed consent. I close by highlighting briefly issues that are of common concern across different fundamental normative frameworks for health policy. PMID- 27259289 TI - Capsule Commentary on Kok et al., Risk of Autoimmune Disease in Adults with Chronic Insomnia Requiring Sleep-Inducing Pills: A Population-Based Longitudinal Study. PMID- 27259290 TI - Variation in Specialty Outpatient Care Patterns in the Medicare Population. AB - BACKGROUND: Multiple payment reform efforts are under way to improve the value of care delivered to Medicare beneficiaries, yet few directly address the interface between primary and specialty care. OBJECTIVE: To describe regional variation in outpatient visits for individual specialties and the association between specialty physician-specific payments and patient-reported satisfaction with care and health status. DESIGN: Retrospective cross-sectional study. PATIENTS: A 20 % random sample of Medicare fee-for-service beneficiaries in 2012. MAIN MEASURES: Regions were grouped into quartiles of specialist index, defined as the observed/expected regional likelihood of having an outpatient visit to a specialist, for ten common specialties, adjusting for age, sex, and race. Outcomes were per capita specialty-specific physician payments and Medicare Current Beneficiary Survey responses. KEY RESULTS: The proportion of beneficiaries seeing a specialist varied the most for endocrinology and gastroenterology (3.7- and 3.9-fold difference between the highest and lowest quartiles, respectively) and least for orthopedics and urology (1.5- and 1.7-fold difference, respectively). Multiple analyses suggested that this variation was not explained by prevalence of disease. Average specialty-specific payments were strongly associated with the likelihood of visiting a specialist. Differences in per capita payments from lowest (Q1) to highest quartiles (Q4) were greatest for cardiology ($89, $135, $172, $251) and dermatology ($46, $64, $82, $124). Satisfaction with overall care (median [interquartile range] across specialties: Q1, 93.3 % [92.6-93.7 %]; Q4, 93.1 % [92.9-93.2 %]) and self-reported health status (Q1, 37.1 % [36.9-37.7 %]; Q4, 38.2 % [37.2-38.4 %]) was similar across quartiles. Satisfaction with access to specialty care was consistently lower in the lowest quartile of specialty index (Q1, 89.7 % [89.2-91.1 %]; Q4, 94.5 % [94.4-94.8 %]). CONCLUSIONS: Substantial regional variability in outpatient specialist visits is associated with greater payments with limited benefits in terms of patient-reported satisfaction with care or reported health status. Reducing outpatient physician visits may represent an important opportunity to improve the efficiency of care. PMID- 27259292 TI - Propionibacterium namnetense sp. nov., isolated from a human bone infection. AB - A polyphasic taxonomic study was performed on two Gram-positive-staining, anaerobic, pleomorphic, rod-shaped strains isolated from human bone and tissue samples. Sequencing of the 16S rRNA genes revealed that the strains belong to a novel species within the genus Propionibacterium, most closely related to Propionibacterium acnes subsp. acnes and Propionibacterium acnes subsp. elongatum with similarity values of 98.4 % and 98.1 %, respectively. In addition, protein coding genes for rpoB, recA and gyrB clearly separated the novel organism from all species and subspecies of the genus Propionibacterium. However, a DNA-DNA hybridization analysis between the novel organism and the type strain P. acnes ATCC 6919T revealed a value of only 61.1 %. Furthermore, whole genome analysis using the program OrthoANI gave a value of 88.5 %, which is significantly below the cut-off value of 95 % for species delineation. The major fatty acids were iso C15 : 0, anteiso-C15 : 0 and iso-C17 : 0. The DNA G+C content of the type strain was 59.7 mol%. When taken collectively, phenotypic, molecular genetic, chemotaxonomic and phylogenetic information demonstrate that the organism represents a distinct, albeit close relative of P. acnes On the basis of the results presented, the organism represents a novel member of the genus Propionibacterium for which the name Propionibacterium namnetense sp. nov. is proposed. The type strain is NTS 31307302T (=DSM 29427T=CCUG 66358T). PMID- 27259291 TI - Quantifying the Severity of a Delirium Episode Throughout Hospitalization: the Combined Importance of Intensity and Duration. AB - BACKGROUND: The ability to determine which episodes of delirium are likely to lead to poor clinical outcomes has remained a major area of challenge. OBJECTIVE: To quantify delirium severity and course over an entire hospitalization using several measures, and to evaluate their predictive validity for 30- and 90-day outcomes post-discharge. DESIGN: Two prospective cohort studies. PARTICIPANTS: Analysis was conducted in two independent cohorts of adult patients aged >=70. MAIN MEASURES: Nine delirium episode severity measures were examined: (1) measures reflecting delirium intensity (peak Confusion Assessment Method-Severity [CAM-S] and mean CAM-S score), (2) a measure reflecting delirium intensity and duration (sum of all CAM-S scores, sum of all CAM-S scores on delirium days only, peak CAM-S score x days with delirium), (3) measures requiring information on delirium duration and delirium at discharge (total number of delirium days, percentage of delirium days, delirium at discharge), and (4) a measure of cognitive change. Associations of the delirium episode severity measures with 30- and 90-day post-hospital outcomes (death, nursing home placement, and readmission) relevant to delirium were examined. KEY RESULTS: The delirium episode severity measure that required information on both delirium intensity and duration (sum of all CAM-S scores) was the most strongly associated with 30- and 90-day post-hospital outcomes. Using this measure, the relative risk [95 % confidence interval] for death at 30-days increased across levels of sum of all CAM-S scores from 1.0 (referent) to 2.1 [0.8, 5.4] for 'low,' to 2.9 [1.2, 7.1] for 'moderate,' to 6.4 [2.9, 14.0] for 'high' (p for trend <.01). CONCLUSIONS: The delirium episode severity measure that included both intensity and duration had the strongest association with important post-hospital outcomes. PMID- 27259293 TI - Canine influenza virus coinfection with Staphylococcus pseudintermedius enhances bacterial colonization, virus load and clinical presentation in mice. AB - BACKGROUND: Canine influenza virus (CIV) and Staphylococcus pseudintermedius (Sp) are pathogens that cause respiratory disease in dogs. Considering bacterial infections following influenza are a leading cause of illness and death, it is of particular meaning to investigate the interaction between these two pathogens. In this study, BALB/c mice were used as a mouse model to assess whether inoculation with CIV H3N2 followed by S. pseudintermedius 72 h later resulted in exacerbation of disease. Disease was characterized by assessment of body weight loss, titration of virus and bacteria, histopathology, and cytokine production. RESULTS: There was a significantly greater decrease in body weight in the co infected group compared with the CIV-only and SP-only groups. CIV inoculation increased bacterial colonization, whereas secondary infection with S. pseudintermedius elevated the viral RNA load of CIV in tissues. The histological lesions in the brain, spleen and lung were more severe in the CIV/Sp group than in the singly treated groups. Infection with CIV alone, Sp alone or coinfection stimulated a significantly higher release of cytokines, such as interferon-gamma (IFN)-gamma, interleukin 6 (IL)-6, tumor necrosis factor (TNF-alpha) and lymphotactin (Lptn), than was observed in the mock-infected group (PBS). Moreover, the levels of IFN-gamma in the spleen and lung were higher in the CIV/Sp group compared with the CIV-only and Sp-only groups. CONCLUSION: Our findings provide the first demonstration that the secondary infection of mice with Sp leads to increased clinical signs and lesions during canine influenza. PMID- 27259294 TI - Unanticipated coordination of tris buffer to the Radical SAM cluster of the RimO methylthiotransferase. AB - Radical SAM enzymes generally contain a [4Fe-4S](2+/1+) (RS cluster) cluster bound to the protein via the three cysteines of a canonical motif CxxxCxxC. The non-cysteinyl iron is used to coordinate SAM via its amino-carboxylate moiety. The coordination-induced proximity between the cluster acting as an electron donor and the adenosyl-sulfonium bond of SAM allows for the homolytic cleavage of the latter leading to the formation of the reactive 5'-deoxyadenosyl radical used for substrate activation. Most of the structures of Radical SAM enzymes have been obtained in the presence of SAM, and therefore, little is known about the situation when SAM is not present. In this report, we show that RimO, a methylthiotransferase belonging to the radical SAM superfamily, binds a Tris molecule in the absence of SAM leading to specific spectroscopic signatures both in Mossbauer and pulsed EPR spectroscopies. These data provide a cautionary note for researchers who work with coordinative unsaturated iron sulfur clusters. PMID- 27259296 TI - Steering intermediate courses: desert ants combine information from various navigational routines. AB - A number of systems of navigation have been studied in some detail in insects. These include path integration, a system that keeps track of the straight-line distance and direction travelled on the current trip, the use of panoramic landmarks and scenery for orientation, and systematic searching. A traditional view is that only one navigational system is in operation at any one time, with different systems running in sequence depending on the context and conditions. We review selected data suggesting that often, different navigational cues (e.g., compass cues) and different systems of navigation are in operation simultaneously in desert ant navigation. The evidence suggests that all systems operate in parallel forming a heterarchical network. External and internal conditions determine the weights to be accorded to each cue and system. We also show that a model of independent modules feeding into a central summating device, the Navinet model, can in principle account for such data. No central executive processor is necessary aside from a weighted summation of the different cues and systems. Such a heterarchy of parallel systems all in operation represents a new view of insect navigation that has already been expressed informally by some authors. PMID- 27259297 TI - A Mouse Model of Hypospadias Induced by Estradiol Benzoate. AB - We wished to establish a mouse model of hypospadias using injections of estradiol benzoate for investigating the molecular mechanisms of hypospadias. Fifty timed pregnant mice were randomly divided into five study groups: A, B, C, D, and E. These groups were injected subcutaneously with estradiol benzoate mixed with sesame oil at, respectively, the doses of 0, 0.1, 0.5, 2.5, or 12.5 mg kg(-1) days(-1) from gestation day (GD) 12 to GD 16. The pups' mortality was recorded on the day of delivery. Urethras and positions of testes were examined on postnatal day 28. The numbers of live pups were significantly lower in the study groups D and E compared to study group A (p < 0.01). Hypospadias was seen in groups C (3.3 %; 1/30), D (18.2 %; 4/22), and E (21.4 %; 3/14), while cryptorchidism was observed in groups C (10 %; 3/30), D (31.8 %; 7/22), and E (57.1 %; 8/14) on postnatal day 28. The experimental model of hypospadias induced by estradiol benzoate in the group D (2.5 mg kg(-1) days(-1)) was more reliable considering high mortality of the study group E. The dose of estradiol benzoate used in the group D is suitable for establishing mouse model of hypospadias. PMID- 27259295 TI - Neuroprotection by Epigenetic Modulation in a Transgenic Model of Multiple System Atrophy. AB - Similar to Parkinson disease, multiple system atrophy (MSA) presents neuropathologically with nigral neuronal loss; however, the hallmark intracellular alpha-synuclein (alphaSyn) accumulation in MSA affects typically oligodendrocytes to form glial cytoplasmic inclusions. The underlying pathogenic mechanisms remain unclear. As MSA is predominantly sporadic, epigenetic mechanisms may play a role. We tested the effects of the pan-histone deacetylase inhibitor (HDACi) sodium phenylbutyrate in aged mice overexpressing alphaSyn under the control of the proteolipid protein promoter (PLP-alphaSyn) designed to model MSA and characterized by alphaSyn accumulation in oligodendrocytes and nigral neurodegeneration. HDACi improved motor behavior and survival of nigral neurons in PLP-alphaSyn mice. Furthermore, HDACi reduced the density of oligodendroglial alphaSyn aggregates, which correlated with the survival of nigral neurons in PLP-alphaSyn mice. For the first time, we suggest a role of HDACi in the pathogenesis of MSA-like neurodegeneration and support the future development of selective HDACi for MSA therapy. PMID- 27259298 TI - Type II Diabetes Patients with Proteinuria and the Recovery of Their Metabolic Parameters. AB - The aim of this study is to provide reasonable guidelines for type II diabetes patients with proteinuria to recover their metabolic parameters. A cross sectional study was conducted in selected groups of type 2 diabetic patients. Hypoglycemic and antihypertensive drug use was recorded. Certain physical examinations were conducted including routine urine test, urinary albumin/creatinine ratio, metabolic parameters of blood glucose and lipid, and other biochemical indicators. Medication and metabolic indicators were compared between the groups based on the seriousness of the proteinuria. A total of 923 cases were selected for this study, with an average age of 63 years. Based on the proteinuria contents, the cases were divided into three groups of proteinuria negative, microalbuminuria, and clinical proteinuria. The recovery rates of the blood pressure control for the groups were 44.2, 35.3, and 36.3 %, respectively. The glycated hemoglobin control recovery rates were 22.2, 18.5, and 15.2 % in the groups. The groups' triglyceride control satisfaction rates were 44.4, 43.3, and 39.8 %. The satisfaction rates of total cholesterol control were 34.5, 26.8, and 25.7 %, respectively and the satisfaction rates of LDL-c control of the three groups were 30.6, 23.8, and 22.1 %. This indicated an unregulated use of hypoglycemic agents, antihypertensives, and lipid-lowering drugs and low recovery rates for metabolic indicators of the cases. Among the 923 cases, 397 had microalbuminuria or clinical proteinuria, and only 22 patients took angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB) as antihypertensive drugs. The use of antihypertensive drugs is not standardized, and only a small portion of patients were treated with ACEI or ARB drugs. Therefore, the proteinuria in diabetic patients should be timely screened and evaluated, as well as renal and metabolic function comprehensively regulated and antihypertensives and lipid-lowering drugs rationally used. PMID- 27259299 TI - The Impact of Small RNA Interference Against Homer1 on Rats with Type 2 Diabetes and ERK Phosphorylation. AB - The objective of the study is to evaluate Homer1 expression in rats with Type 2 diabetes mellitus (T2DM) and investigate the mechanism by which Homer1 influences the pathogenesis of diabetes through study on rat model with decreased Homer1 expression. Rat model of T2DM was constructed and blood insulin concentration was measured. Homer1 mRNA and protein expressions in rat pancreatic tissue were determined using RT-PCR as well as Western blotting. Homer1 expression in human monocytic THP-1 cells was interfered using short hairpin RNA, and its effect on phosphorylation of extracellular signal-regulated kinase (ERK) was assessed. Fasting glucose concentration in rat model of T2DM was significantly higher than that of normal rats (13.1 +/- 2.4 vs 5.1 +/- 1.1 mmol/L), and fasting blood insulin concentration of diabetic group was significantly lower than that of normal group (13.6 +/- 1.9 18.3 +/- 2.2 mIU/L) (P < 0.05). Homer1 mRNA and protein expressions in pancreatic tissue of rats with T2DM were significantly higher than those of normal rats (P < 0.05). Level of ERK phosphorylation in pancreatic tissue of rats with T2DM was significantly higher than that of normal rats. Homer1 mRNA level in rat pancreatic tissue of T2DM was positively correlated with the area of pancreatic islets (r = 0.526, P = 0.014). Homer1 mRNA level was significantly inhibited in high-glucose and high-fat stimulated human monotypic THP-1 cells with interfered Homer1. Compared with controls, P-ERK phosphorylation was significantly decreased in THP-1 cells with interfered Homer1 (P < 0.05). Homer1 can promote the progression of T2DM, which may be achieved through affecting ERK phosphorylation. PMID- 27259300 TI - Tirofiban Combined with Fondaparinux for Post-PCI Treatment of Patients with Acute Coronary Syndrome and Mild Renal Insufficiency. AB - Proper administration of antithrombotic and antiplatelet drugs after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and renal insufficiency is a challenging task. In this study, we utilized Fondaparinux and Tirofiban (either separately or combined) to treat post-PCI patients with ACS and concurrent renal insufficiency. The patients were followed up for 1 year. We observed that combined treatment led to a higher number of significant therapeutic effects and better reduced the frequency of bleeding events. Our findings indicate that combined antithrombotic and antiplatelet treatment improves the prognosis in patients with ACS and renal insufficiency who received PCI treatment. PMID- 27259301 TI - Calcitonin Gene-Related Peptide-Induced Calcium Alginate Gel Combined with Adipose-Derived Stem Cells Differentiating to Osteoblasts. AB - Calcitonin gene-related peptide (CGRP) has been confirmed with induction osteoblastic differentiation, but if it can make the three-dimensional culture of adipose-derived stem cells (ADSCs) to the osteoblastic differentiation, thus constructing tissue-engineered bone rare reports. To investigate the feasibility of exogenous CGRP-induced calcium alginate gel combined with ADSCs from rabbits in three-dimensional condition to construct tissue-engineered bone. ADSCs were obtained by collagenase I digestion of the subcutaneous adipose tissue of inguinal region of New Zealand rabbits. At the third passage, cells were mixed with sodium alginate to prepare calcium alginate gel, and the cells were assigned into two-group cultivates in 24 orifice plates. ADSCs in the control group were treated with DMEM/F-12 medium supplemented with 10(-2) mol/L beta glycerophosphate sodium, 10(-7)mol/L dexamethasone, 50 mg/L ascorbic acid, 0.1 % volume fraction of fetal bovine serum. ADSCs in the experimental group were incubated with the same medium as above, and in addition 1.5 ug/L CGRP was added. The cells proliferation and the mRNA expressions of collagen I and osteocalcin were detected by MTT and RT-PCR assays, respectively and alkaline phosphatase(ALP)and calcium concentration at different induction time were detected. The cell proliferation curves were S shaped. The OD values of experimental group were higher than those of control group at 1, 3, 5, 7, 14, and 21 days after osteogenic induction (P < 0.05). ALP and alizarin red stains of ADSCs were all positive, but golden round nodes became bigger and more in the experimental group compared with the control group after 2 weeks. At 7 and 14 days, collagen I and osteocalcin mRNA expression were greater in the experimental group than the control group. ALP and calcium concentration of experimental group were higher than that of control group at 1, 2, 3, 4 weeks after osteogenic induction (P < 0.05). Thus, these results show that the CGRP-induced ADSCs combined with calcium alginate gel to osteoblasts differentiation. PMID- 27259302 TI - Significance of Serum Procalcitonin Levels in Differential Diagnosis of Pediatric Pneumonia. AB - The objective of this study was to explore the early diagnosis methods of severe pediatric pneumonia. A total of 65 cases hospitalized in pediatric departments and ICU of our hospital because of severe pneumonia were divided into two groups according to pathogen detection. The groups were as follows: 34 cases of bacterial pneumonia, 32 cases of a non-bacterial pneumonia, and 37 cases of healthy children after physical examination in our hospital as the control group. The peripheral blood was sampled from each of the three groups for procalcitonin (PCT). The pediatric PCT level in peripheral blood of the bacterial pneumonia group was significantly higher than that of non-bacterial pneumonia group and the control group. The statistical differences (each at p < 0.01) and the level of pediatric serum PCT in the bacterial pneumonia group before treatment were statistically different from that in the same group after treatment (p < 0.01), while the level of pediatric serum PCT in non-bacterial pneumonia group before treatment was statistical indifferent from that in the same group after treatment (p > 0.01). PCT level in pediatric peripheral blood is an important diagnostic indicator of bacterial infection and a sensitive indicator of distinction between bacterial pneumonia and the non-bacterial pneumonia, thus being of great significance for clinical and differential diagnosis. PMID- 27259303 TI - A Rapid and Sensitive UPLC-MS/MS Method for Determination of Docetaxel in Rabbit Plasma: Pharmacokinetic Study of New Lung-Targeting Docetaxel Liposome at Low Dose. AB - In this study, a more rapid and more sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method is developed and validated for the pharmacokinetic study of a new lung-targeting docetaxel liposome (DTX-LP) at low dose (1 mg/kg) in rabbits. The method is reliable and reproducible with intra-day precision below 5.75 %, inter-day precision below 7.57 %, and mean extraction recovery of 84.1-91.7 %. At low dose, the validated method is successfully applied to the comparative pharmacokinetic study of docetaxel (DTX) in rabbit plasma after intravenous administration of DTX-LP and DTX injection, respectively. The results indicate that the pharmacokinetic profile of DTX is completely changed when loaded in the new type of liposome, which can make DTX quicker distribution from the circulation to the target organ and slower eliminated from the body. PMID- 27259304 TI - High levels of Phosphatase and Tensin Homolog Expression Predict Favorable Prognosis in Patients with Non-small Cell Lung Cancer. AB - The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 vs. 12.9 months, log rank P = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 vs. 15.54 months, log rank P = 0.043). High levels of PTEN expression resulted in 43 % reduction in risk for all NSCLC patients (HR 0.57, 95 % CI 0.33-0.98, P = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex, and tumor type (HR 0.56, 95 % CI 0.32 0.99; P = 0.048; HR 0.54, 95 % CI 0.36-0.97; P = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (P > 0.17). When levels of PTEN expression were binarized using the optimal cut-point, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80 and 58 %, respectively, P = 0.049) and in patients with AC than in those with squamous-cell carcinoma (78 and 58 %, respectively, P = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (P > 0.28). Our results suggest that high levels of PTEN expression may be favorable prognostic markers in NSCLC patients. PMID- 27259305 TI - Study of the Changes of Acrosomal Enzyme, Nitric Oxide Synthase, and Superoxide Dismutase of Infertile Patients with Positive Antisperm Antibody in Seminal Plasma. AB - The purpose of this article is to study the effect of positive antisperm antibody (AsAb) in seminal plasma on acrosomal enzyme activity, nitric oxide synthase (NOS) activity, and superxide dismutase (SOD) activity of spermatozoa. A total of 40 infertility patients with positive AsAb in seminal plasma were selected as experimental group, and 40 fertile males were selected as control group. Based on the changes in absorbance, the acrosomal enzyme activity was detected by the BAEE/ADH method, the NOS activity was detected by the redoxreaction assay, and SOD level was measured with xanthine oxidase method. Compared with the control group, acrosomal enzyme activity of spermatozoa of the experimental group was significantly decreased (P < 0.01), NOS activity was apparently increased (P < 0.01), and the SOD level in seminal plasma was significantly decreased (P < 0.01). The infertility caused by positive AsAb in seminal plasma may be related to the changes in the acrosomal enzyme of spermatozoa and the SOD and NOS activities in seminal plasma. PMID- 27259306 TI - Comparison of SPE, IFE, and FLC in Monitoring Patients with Multiple Myeloma After Autologous Stem Cell Transplantation. AB - Conventionally, serum protein electrophoresis (SPE) and serum immunofixation electrophoresis (IFE) are used as primary methods to diagnose and monitor multiple myeloma (MM). Recently, serum-free light chain (FLC) assay has been incorporated into hematological screening programs for myeloma. The purpose of this study is to compare the performance of the three methods in monitoring MM patients after autologous stem cell transplantation (ASCT). SPE, serum IFE and serum FLC assay were performed on 38 MM patients who underwent ASCT. In total, four patients had unexpected protein bands (UPBs) and 13 patients had relapsed after ASCT. Our results indicate that IFE is more sensitive than SPE and FLC assay in detection of UPBs and relapse. The results of IFE may provide useful information in advance of patient relapse. PMID- 27259307 TI - Polyphenols in Health and Disease. AB - Deadly diseases, such as cardiovascular diseases and cancer, remain the major health problems worldwide. Research in cardiovascular diseases and genome-wide association studies were successful in indentifying the gene loci associated with these threatening diseases. Yet, a substantial number of casual factors remain unexplained. Over the last decade, a better understanding of molecular and biochemical mechanisms of cardiac diseases led to developing a rationale for combining various protective agents, such as polyphenols, to target multiple signaling pathways. The present review article summarizes recent advances of the use of polyphenols against diseases, such as cardiac diseases. PMID- 27259308 TI - Inhibitory Effects and Sympathetic Mechanisms of Distension in the Distal Organs on Small Bowel Motility and Slow Waves in Canine. AB - Rectal distension (RD) is known to induce intestinal dysmotility. Few studies were performed to compare effects of RD, colon distension (CD) and duodenal distension (DD) on small bowel motility. This study aimed to investigate effects and underlying mechanisms of distensions in these regions on intestinal motility and slow waves. Eight dogs chronically implanted with a duodenal fistula, a proximal colon fistula, and intestinal serosal electrodes were studied in six sessions: control, RD, CD, DD, RD + guanethidine, and CD + guanethidine. Postprandial intestinal contractions and slow waves were recorded for the assessment of intestinal motility. The electrocardiogram was recorded for the assessment of autonomic functions. (1) Isobaric RD and CD suppressed intestinal contractions (contractile index: 6.0 +/- 0.4 with RD vs. 9.9 +/- 0.9 at baseline, P = 0.001, 5.3 +/- 0.2 with CD vs. 7.7 +/- 0.8 at baseline, P = 0.008). Guanethidine at 3 mg/kg iv was able to partially block the effects. (2) RD and CD reduced the percentage of normal intestinal slow waves from 92.1 +/- 2.8 to 64.2 +/- 3.4 % (P < 0.001) and from 90 +/- 2.7 to 69.2 +/- 3.7 % (P = 0.01), respectively. Guanethidine could eliminate these inhibitory effects. (3) DD did not induce any changes in small intestinal contractions and slow waves (P > 0.05). (4) The spectral analysis of the heart rate variability showed that both RD and CD increased sympathetic activity (LF) and reduced vagal activity (HF) (P < 0.05). Isobaric RD and CD could inhibit postprandial intestinal motility and impair intestinal slow waves, which were mediated via the sympathetic pathway. However, DD at a site proximal to the measurement site did not seem to impair small intestinal contractions or slow waves. PMID- 27259309 TI - Evaluation of Immunosuppressive Activity of Demethylzeylasteral in a Beagle Dog Kidney Transplantation Model. AB - Several monomers isolated from Tripterygium wilfordii Hook f. (Celastraceae) have attracted worldwide interest. In this study, we established a simple and reliable kidney transplantation model in beagle dog to evaluate the immunosuppressive activity of demethylzeylasteral (T-96), an immunosuppressive monomer isolated from the root xylem of T. wilfordii. Recipient and donor male beagle dogs were obtained from two different breeders to ensure MHC mismatching. All dogs were randomly divided into six groups following kidney transplantation, and different doses of T-96 or cyclosporine A (CsA) were administered to each group during 14 days of observation. The results showed that T-96 alone at a dosage of 10 or 20 mg/kg/day prolonged graft survival up to 10.83 +/- 1.47 or 11.17 +/- 1.47 days. A combination of T-96 and CsA significantly prolonged the survival time to 13.33 +/ 1.75 days. The results demonstrated that T-96 can inhibit acute rejection in kidney transplantation, and the inhibitory effect of T-96 was enhanced when combined with CsA, which suggests the possible use in organ transplantation to prevent immune rejection. PMID- 27259310 TI - Curcumin Promotes Cell Cycle Arrest and Inhibits Survival of Human Renal Cancer Cells by Negative Modulation of the PI3K/AKT Signaling Pathway. AB - Curcumin possesses anti-cancer effects. In the current study, we tested the effect of curcumin on cell proliferation, viability, apoptosis, cell cycle phases, and activation of the PI3K/Akt pathway in the renal cell carcinoma (RCC) cell line RCC-949. We observed that cell proliferation and viability were markedly inhibited by curcumin, while cell apoptosis was promoted. The latter effect was associated with increased expression of Bcl-2 and diminished expression of Bax (both: mRNA and protein). The cells treated with curcumin increasingly went into cell cycle arrest, which was likely mediated by diminished expression of cyclin B1, as seen in curcumin-treated cells. In addition, curcumin decreased activation of the PI3K/AKT signaling pathway. In conclusion, our results demonstrate that curcumin exerts anti-cancer effects by negative modulation of the PI3K/AKT signaling pathway and may represent a promising new drug to treat RCC. PMID- 27259311 TI - The Effects of Ephedrine and Phenylephrine on Placental Vascular Resistance During Cesarean Section Under Epidual Anesthesia. AB - The purpose of this article is to study the effect of ephedrine and phenylephrine on placental vascular resistance during cesarean section under epidural anesthesia via Doppler ultrasonography. Sixty female subjects, scheduled for elective cesarean section and had an intrathecal injection of bupivacaine, were randomly divided into two groups to receive phenylephrine (50 MUg/min) or ephedrine (4 mg/min) via titration to maintain systolic blood pressure at baseline. Doppler ultrasonography was used to measure baseline vascular resistance values prior to administration of anesthesia, and resistance index (RI) and systolic peak velocity/diastolic velocity (S/D) values of umbilical artery and uterine artery were measured at each time point within first 20 min following intrathecal injection. Blood samples were collected from umbilical artery and umbilical vein during delivery to assess the blood gas values. No significant differences in RI and S/D values of umbilical artery and uterine artery after intrathecal injection were found between two groups. RI and S/D values of uterine artery slightly increased in both groups at each time point after anesthesia, but remained within the normal range. No significant differences were observed in blood gas values and the total amount of vasoconstriction drugs between two groups. In contrast to previous reports that used animal models, our study did not show increased placental vascular resistance in patients following phenylephrine (50 MUg/min) or ephedrine (4 mg/min) infusion, as well as no significant differences in the effect of either of these two. The discrepancy between the results of human and animal studies may be related to species differences and the mechanism of human placental vascular remodeling. PMID- 27259312 TI - The Effect of PSD-93 Deficiency on the Expression of Early Inflammatory Cytokines Induced by Ischemic Brain Injury. AB - The aim of the study was to explore the effect of PSD-93 deficiency on the expression of early inflammatory cytokines induced by cerebral ischemia/reperfusion injury. Ten- to twelve-week-old male PSD-93 knockout (PSD-93 KO) mice (C57BL/6 genetic background) and wild-type (WT) littermates were randomly divided into sham and ischemia/reperfusion (I/R) group. The focal cerebral I/R model was established by middle cerebral artery occlusion (MCAO) suture method. RT-PCR was used to detect the mRNA expression of IL-6, IL-10, Cox 2, iNOS, and TNF-alpha4h following reperfusion. Infarct volume at different time points after I/R was analyzed using 2,3,5-triphenyl tetrazolium staining, and neurological damage score (neurological severity scores, NSS) was used to evaluate the effect of PSD-93 gene knockout on the MCAO-induced neurological injury. In WT mice, early I/R injury led to the increase in the mRNA expression of proinflammatory cytokines IL-6, Cox-2, iNOS, and TNF-alpha that coincided with the decrease in the expression of anti-inflammatory cytokine IL-10, as compared to the sham group (P < 0.05). This effect was markedly attenuated by depleting PSD-93 levels by gene knockout. As compared to sham group, in PSD-93 KO mice I/R4h led to downregulation of Cox-2 and iNOS expression, and increase in the mRNA levels of IL-10 (P < 0.05). In addition, following MCAO, PSD-93 KO mice exhibited improved NSS and reduced infarct volumes, as compared with WT animals. PSD-93 knockout may play a neuroprotective role by mediating the early release of inflammatory cytokines induced by cerebral ischemia. PMID- 27259313 TI - Low-Dose Topical 5-Aminolevulinic Acid Photodynamic Therapy in the Treatment of Different Severity of Acne Vulgaris. AB - The objective of this article is to investigate the effectiveness and safety of photodynamic therapy (PDT) with 3.6 % topical aminolevulinic acid (ALA) and a short incubation time with red light in moderate to severe acne. One hundred and thirty-six patients with moderate to severe acne were treated with 3.6 % topical ALA-PDT for three sessions with an interval of 2 weeks. Patients were evaluated for efficacy and safety on week 2, 4, 6, 8, and 12 after the initial treatment. Most patients showed apparent clearance of acne lesions at the treated site after three sessions. The effective treatment rates were increased after the multiple therapies. The clinical outcomes are the best at 4 weeks after the final treatment. The total effectiveness rate and cure rate of the low-dose ALA-PDT procedure is 92.65 and 47.06 %, respectively. Thirty-one patients and nineteen patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment, respectively, but all of them showed good or excellent improvement after a three-course treatment. A few patients showed mild relapse including papules and comedos at 8 weeks after the final treatment. No significant differences are found in the effects of different acne severity and different genders. Adverse reactions are mild and transient. A 3.6 % topical ALA-PDT with a short time incubation with red light is a simple and an effective treatment option for moderate to severe acne with mild side effects in Chinese people. PMID- 27259314 TI - Cardioprotective Effect of Anisodamine Against Myocardial Ischemia Injury and its Influence on Cardiomyocytes Apoptosis. AB - Anisodamine is an ancient Chinese medicine derived from Tibet as a belladonna alkaloid, which is usually used for improvement of blood circulation in patients with organ phosphorus poisoning or shock. In this study, for the first time, we report its cardioprotective effects on preventing ischemia/reperfusion (I/R) injury of patients with acute myocardial infarction (AMI), and decreasing the myocardial infarction area and severity in heart of Sprague-Dawley (SD) rats. Our results suggest a potential molecular mechanism of anisodamine against the I/R injury in cardiomyocytes is associated with its anti-apoptotic effect. Anisodamine treatment decreases the expression of caspase-3 and caspase-8, and increases Bcl-2/Bax ratio in cardiomyocytes. Our data suggest that anisodamine can provide significant cardioprotection against I/R injury, potentially through the suppression of cardiomyocytes apoptosis. PMID- 27259315 TI - Pharmacodynamics and Pharmacokinetics of Levobupivacaine Used for Epidural Anesthesia in Patients with Liver Dysfunction. AB - The objective of this study was to study the pharmacodynamics and pharmacokinetics of levobupivacaine used for epidural anesthesia in patients with liver dysfunction. Twenty patients aged 20-60, American Society of Anesthesiologists (ASA) graded I-III according to the ASA guidelines, scheduled for elective upper abdominal surgery, were included in the study. They were divided into two groups of ten each. In group I, the patients with liver dysfunction were included, whereas group II was composed of those with normal liver function. In both groups, anesthesia was induced by general anesthesia combined with epidural block, given by T 8-9 interspace injection of 1.8 mg kg( 1) levobupivacaine (0.75 %) with 5 MUg mL(-1) of adrenaline in 1.5 min. The sensory and motor blockade indices were recorded for 30 min after the injection. The plasma concentration of levobupivacaine was determined by high performance liquid chromatography from 0 to 1440 min after the injection and pharmacokinetics of the drug were calculated. The onset and recovery time from the sensory block in the two groups were similar with no significant difference (P > 0.05). The maximum spread of anesthetic effect, the number of spinal segments regressed, onset time, and degree of motor block after the injection were also insignificantly different in the two groups. The plasma levobupivacaine concentration/time curve of the liver dysfunction (group I) was significantly higher than that of the controls (group II). In the liver dysfunction patients, the volume of distribution (V/F) was significantly increased, the elimination rate, i.e., half-life (t 1/2beta ), was prolonged, and the elimination rate constants (K 12 and K 10) were significantly decreased (P < 0.05 or P < 0.01). The patients with liver dysfunction injected with 0.75 % levobupivacaine exhibited normal onset and recovery time of the sensory and motor blocks within 30 min. However, in these patients, the metabolism of levobupivacaine was significantly slower as evidenced by the higher blood concentration of the drug than in cases with normal functioning liver. PMID- 27259316 TI - A New Ex Vivo Method for Effective Expansion and Activation of Human Natural Killer Cells for Anti-Tumor Immunotherapy. AB - Preserving the activities of natural killer (NK) cells in human peripheral blood mononuclear cells (PBMCs) after ex vivo expansion and activation is critical for NK cell-based therapy. Collected from human PBMCs, the NK cells were expanded and activated. The expressions of surface receptors, cytotoxicity against tumor cells, and antibody-dependent cell-mediated cytotoxicity (ADCC) of the NK cells before and after expansion and activation were, respectively, compared. After expansion, the ADCC activity of healthy human NK cells was improved by 32 %, and the cytotoxicity against four types of tumor cells was increased by 19, 29, 26, and 28 %, respectively. The positive expression rates for the activating receptors NKG2D, CD94, NKp46, NKp30, and NKp44 of healthy human NK cells expanded ex vivo were increased by 60, 40, 20, 40, and 63 %, respectively, whereas those for the inhibitory receptors CD158b, NKB1, and NKAT showed no significant changes. The addition of an immunologically active peptide, "TKD," during cell expansion further increased NK cytotoxicity by approximately 10 %. The expanded and activated NK cells from cancer patients achieved average purity which was greater than 90 %, and the cytotoxicity against K562 cells was increased by more than 17 %. Compared with resting NK cells, NK cells both from healthy volunteers and cancer patients expanded and activated ex vivo using our method were significantly more active and demonstrated significantly increased anti-tumor activity. This method could be therefore used as a new and effective approach to meet requirements for anti-tumor immunotherapy. PMID- 27259317 TI - Influence of Intensity-Modulated Radiation Therapy on the Life Quality of Patients with Nasopharyngeal Carcinoma. AB - The present study intends to explore the influence of intensity-modulated radiation therapy on the quality of life for patients with nasopharyngeal carcinoma, which provides a theoretical basis and practical foundation for clinical practice. The present study randomly enrolled 130 cases of patients with nasopharyngeal carcinoma (NPC) in different stages who were admitted in The Second Affiliated Hospital of Fujian Medical University and the First Affiliated Hospital of Chongqing Medical University from September 2007 to August 2012, including 65 cases in IMRT group who received intensity-modulated radiation therapy and 65 cases in CRT group who received conventional radiation therapy. The prescribed dose in the target region of radical radiation therapy was 72 Gy/36 f; the prescribed dose in the target region at high risk was 60-64 Gy/30-32 f; the prescribed dose in the target region at low risk was 50-54 Gy/25-27 f and 2 Gy/f, with conventional fractionated irradiation of 1 f/d and 5 f/w. The data of the quality of life for patients with NPC who received intensity-modulated radiation therapy and conventional radiation therapy were collected and analyzed by filling in the questionnaire survey, including the Quality of Life Questionnaire of Head and Neck 35 (QLQ-H&N35) and Shot Form 36 Health Survey Questionnaire (SF-36). RP, VT, BP, SF, and RE scores in eight fields in SF-36 Scale were declined during the radiation therapy and risen again after radiation therapy, and those measured at 6 months after radiation therapy were higher than those before radiation therapy (all P < 0.05). The scores in IMRT group measured at two and six months after radiation therapy were all higher than those in CRT group (all P < 0.05). The scores of head and neck pain, pararthria, dysphagia, social difficulty, sensory difficulty, difficulty in feeding, xerostomia, cough, sticky saliva, and sensory discomfort during the radiation therapy were lower than those before radiation therapy (all P < 0.05). Except for the scores of sticky saliva and xerostomia, the other scores measured at 6 months after radiation therapy were all lower than those before radiation therapy, and the scores of dysphagia, sticky saliva, and xerostomia in MRT group were lower than those in CRT group (all P < 0.05). Conventional radiation therapy and intensity modulated radiation therapy can cause a decline the quality of life for the patient with head and neck cancer, but intensity-modulated radiation therapy can improve local tumor control rate and significantly reduce the incidence of adverse reactions. PMID- 27259318 TI - Effects of TGF-beta1 on the Proliferation and Apoptosis of Human Cervical Cancer Hela Cells In Vitro. AB - To investigate the effects of TGF-beta1 on the proliferation and apoptosis of cervical cancer Hela cells in vitro. Human cervical cancer Hela cells were cultured in vitro and divided into the experimental and control groups. In the experimental groups, Hela cells were stimulated with different concentrations of TGF-beta1 (0.01, 0.1, 1, and 10 ng/mL), while Hela cells cultured in serum-free medium without TGF-beta1 were used as controls. The CCK8 method was adopted to detect the effect of TGF-beta1 on Hela cell proliferation, and flow cytometry was used to determine cell apoptosis 72 h after TGF-beta1 treatment. Compared with the control group, the CCK-8 tests showed that different concentrations of TGF beta1 had no obvious effect on Hela cell proliferation 24 h after treatment (P > 0.05). However, upon 48 or 72 h of treatment, TGF-beta1 significantly inhibited the proliferation of Hela cells in a time- and dose-dependent manner (P < 0.05). The flow cytometry results indicated that TGF-beta1 influenced the apoptosis of human cervical cancer Hela cells in a dose-dependent manner after 72 h of treatment (P < 0.05). TGF-beta1 significantly inhibited the growth and induced the apoptosis of human cervical Hela cells in vitro. PMID- 27259319 TI - Study on Clinicopathological Features of Gastrointestinal Stromal Tumor and Relevant Prognostic Factors. AB - The objective of the study is to investigate and analyze clinicopathological features of gastrointestinal stromal tumor (GIST) and relevant prognostic factors. Between September 2008 and April 2014, 168 patients who presented with pathologically confirmed GIST and underwent surgical resection of the tumors in our institution were included in this study. A retrospective study on clinicopathological features of the disease and follow-up study on 1-year, 3 year, and 5-year survival rates were performed. Of 168 patients, 113 were males and 55 females of age ranging from 18 to 78 years (mean age 52.6 +/- 10.1 years). Seventy patients (41.7 %) presented abdominal distension, 74 (44.0 %) abdominal pain, and 82 (48.8 %) bloody stools. Of all patients, 115 (68.4 %) developed tumors in GI tract, 51 (30.4 %) presented multiple tumors, 88 (52.4 %) tumors displayed a maximal diameter >5 cm, mitotic count >5/50HPF were observed in 80 patients. Positive rate of CD117 was 92.9 % (156/12), DOG1 97.0 % (163/5), CD34 53.0 % (89/79) and S-100 25.6 % (43/125). Follow-up study achieved in 149 patients. Survival analysis and Cox regression analysis demonstrated that no significant prognostic effects were observed for gender, clinical presentations, tumor location, number of tumors, CD34 and S-100 expression (p > 0.05). However, tumor diameter and mitotic count were factors with significant effect on prognosis of GIST (p < 0.05). Tumors with diameter >5 cm and mitotic count >=5/50HPF resulted in poor prognosis. Common symptoms of GIST include abdominal pain and blood stools. Tumor diameter and mitotic count are helpful for the evaluation of prognosis with favorable clinical value. PMID- 27259320 TI - Hypoxic Preconditioning Combined with Microbubble-Mediated Ultrasound Effect on MSCs Promote SDF-1/CXCR4 Expression and its Migration Ability: An In Vitro Study. AB - Our objective is to investigate the promoting effect of hypoxic preconditioning combined with microbubble (MB)-mediated ultrasound (US) on the SDF-1/CXCR4 expression and the migration ability of mesenchymal stem cells (MSCs). Based on the uniform design, the parameters of MB-mediated US, such as the total treatment time (T), acoustic intensity (Q), and the dosage of MBs, were optimized firstly. The results were assessed by regression analysis. Using the optimum irradiation parameters, the concentration of SDF-1 in the supernatant, the expression levels of membrane CXCR4, and the cell viability of hypoxic MSCs or normoxic MSCs were compared. The in vitro transwell migration assay was performed as well. The best combination of parameters for more SDF-1 secretion and less MSCs death was T = 30 s, A = 0.6 W/cm(2), and MB = 10(6)/ml. After 24 h of hypoxic preconditioning, the expression of SDF-1 and surface CXCR4 was increased in the hypoxic MSC group as compared to the normoxic MSC group (P < 0.05). On the basis of that, MB-mediated US could further upregulate the expression of SDF-1/CXCR4 with the optimum parameters (P < 0.05), while the cell viability was only decreased by about 9-10 % compared to the untreated groups. The number of successfully migrated cells was also the largest in the hypoxic preconditioning combined with MB-mediated US group than all the other groups. The results obtained indicate the combination of hypoxic preconditioning, and MB-mediated US can upregulate the SDF-1/CXCR4 expression and improve the migration ability in MSCs. PMID- 27259321 TI - Research on Acute Toxicity and Pharmacodynamics of Jinyulian Oral Solution. AB - A research on Jinyulian Oral Solution was conducted and the objectives were to discover its possible acute toxicity and antibacterial effects when used in vitro and in vivo. Regarding the acute toxicity test, Kunming mice were fed a maximum amount of the solution as their stomachs could hold, i.e., 40 mL kg(-1). To ascertain the minimum inhibitory concentration (MIC) of the solution, two types of germs, i.e., Staphylococcus aureus and Escherichia coli, were selected and tube dilution method was adopted. An antibacterial experimental model relying on animals' body was developed for the researchers to observe the solution's antibacterial effects. Test results showed that no abnormalities were discovered within 14 days after the initial date of testing and the mice grew as normal when fed with an amount of the solution 250 times of a normal clinical doze (In this case a man was assumed to weigh 60 kg.) and that the solution demonstrated obvious antibacterial effects on the two types of selected germs. The respective measured MIC50 and MIC90 values of the two germs were 3.2, 12.8, 6.4, and 25.6 mg L(-1). Therefore, it is reasonable to conclude that Jinyulian Oral Solution possesses no acute toxicity but obvious antibacterial effects on the two before mentioned germs. PMID- 27259322 TI - The Expression of HSPD1, SCUBE3, CXCL14 and Its Relations with the Prognosis in Osteosarcoma. AB - The aim of the study was to explore the expression of three genes, HSPD1, SCUBE3, and CXCL14, in osteosarcoma cells and tissue, as well as their association with the prognosis of patients with osteosarcoma. The expression of HSPD1, SCUBE3, and CXCL14 in osteosarcoma cells was detected by using Western blotting method. siRNA was used to knockdown the expression of the three genes. CCK8 cell proliferation assay was used to observe the effect of siRNA interference on U2OS cell proliferation. The expression of the three genes in osteosarcoma tissue was detected employing immunohistochemical method. Kaplan-Meier survival analysis was used to compare the relations between the expression of the three genes and prognosis. The Western blotting results showed that the expression of Hsp70, SCUBE3 protein, and CXCL14 chemotactic factor in osteosarcoma cells was significantly higher than that in normal osteocytes (p < 0.05). After the three genes were interfered by siRNA, the mRNA and protein expression levels of these genes in osteosarcoma cells were significantly decreased (p < 0.05). The growth rate of U2OS cell after the siRNA interference was significantly lower than that before interference and that in the control group transfected with negative control siRNA (p < 0.05). The result of immunohistochemistry demonstrated that the expression of Hsp70, SCUBE3 protein, and CXCL14 chemotactic factor in osteosarcoma tissues was significantly higher than that in adjacent muscle tissue (p < 0.05). Kaplan-Meier survival analysis indicated that the survival rate of the patients with high expression of those three kinds of genes was obviously lower than that of other patients (p < 0.05). There was no significant difference between the survival rates of patients with high or low expression of two genes (p > 0.05). The expression of HSPD1, SCUBE3, and CXCL14 was all high in osteosarcoma tissues and cells; moreover, the three kinds of genes had close correlations with the prognosis of the patients. Targeted inhibition of these three genes could inhibit the proliferation of the tumor, which may become a new therapeutic target. PMID- 27259323 TI - Different Treatment Strategies for Patients with Multivessel Coronary Disease and High SYNTAX Score. AB - We sought to evaluate the prognosis of different treatment strategies on patients with multivessel coronary disease and high SYNTAX score. 171 patients with multivessel coronary disease and SYNTAX score epsilon33, who underwent coronary angiography between July 2009 and July 2010 at our hospital were retrospectively selected and divided into incomplete and complete revascularization intervention groups (IR), a coronary artery bypass surgery group (CABG), a conservative drug therapy group according to treatment strategies chosen and agreed by the patients. These patients were followed up for 19.44 +/- 5.73 months by telephone or outpatient service. We found the medical treatment group has a lower overall survival than the IR, CR group, and CABG group (P log-rank values are 0.03, 0.03, and 0.02, respectively). The medical treatment group also has a lower survival than the IR group, CR group, and CABG group in cerebral stroke and recurrent myocardial infarction (MI) (P log-rank values are 0.004, 0.03, and 0.001, respectively) and MACE events (P log-rank values are 0.003, 0.001 and P < 0.001, respectively). The medical treatment group and IR group have lower survival in recurrent angina pectoris than the CR group and CABG group (P log-rank values are 0.02, 0.02 and 0.03, 0.008, respectively). There are no significant differences between the CR group and the CABG group in number of deaths, strokes and recurrent MIs, MACE events, angina pectoris (P log-rank values are 0.69, 0.53, and 0.86, respectively). The IR group shows a lower survival than the CR group and CABG group only in angina pectoris (P log-rank values are 0.03 and 0.008, respectively). For the patients with a high SYNTAX score, medical treatment is still inferior to revascularization therapy (interventional therapy or coronary artery bypass surgery). It appears that the CABG is not obviously superior to the coronary intervention therapy. Complete revascularization and coronary artery bypass grafting treatments simply have better survival in angina pectoris compared to the incomplete revascularization. Therefore, individual treatment strategies are recommended and more trials are required to study these effects. PMID- 27259324 TI - Transforming Growth Factor beta1 Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells Via Up-Regulation of Connective Tissue Growth Factor. AB - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a poor patient survival. Expression of TGF-beta1 is up-regulated in HCC and is thought to play a crucial role in the occurrence and development of HCC. However, the mechanism of TGF-beta1-mediated facilitation of malignant growth and invasion remains unclear, although some previous studies highlighted a potential involvement of the connective tissue growth factor (CTGF). Here we demonstrate that the in vitro migration of the HCC cell line SMMC-7721 is increased in the presence of recombinant TGF-beta1, and that this effect is reversed by the specific inhibitor SB431542. Furthermore, TGF-beta1 treatment up-regulated the expression of its own mRNA as well as the expression of CTGF mRNA. The TGF-beta1 stimulated migration of SMMC-7721 cells was diminished by siRNA silencing of CTGF. These in vitro observations were validated in a murine xenograft model. In particular, silencing of CTFG diminished the TGF-beta1-induced tumorigenesis in experimental animals. In conclusion, TGF-beta1 plays a critical role in HCC migration and invasion, and this effect is dependent on CTGF. PMID- 27259325 TI - Non-ingested Intraperitoneal Foreign Body Extraction by Transumbilical Endoscopic Surgery in a 2-year-Old Girl. AB - In this article, we present an unusual case of a girl who had a mass present in the right lower quadrant of the abdomen and imaging analysis showed that to be a sewing needle. Patient was admitted electively and taken to the operation theater for removal of a foreign body under general anesthesia. The needle was extracted with transumbilical endoscopic surgery (TUES) without any evidence of intra abdominal organ injury and with a good long-term cosmetic outcome. This case highlights the subtleties of TUES in the management of intra-abdominal foreign bodies in children including rare causes such as non-ingested foreign bodies. PMID- 27259326 TI - Effect of Transcatheter Arterial Chemoembolization Combined with Argon-Helium Cryosurgery System on the Changes of NK Cells and T Cell Subsets in Peripheral Blood of Hepatocellular Carcinoma Patients. AB - Hepatocellular carcinoma (HCC) is one of the most aggressive tumors in humans. T lymphocytes and natural killer (NK) cells are the body's first line of defense to prevent tumor cell growth. Previous studies have demonstrated that transcatheter arterial chemoembolization (TACE) combined with argon-helium cryosurgery system (AHCS) can effectively treat liver cancer. However, the mechanism of the treatment is unclear yet. In the current study, we investigated the effects of TACE combined with AHCS on the changes of T cell subsets and NK cells in peripheral blood of HCC. Our data show that alpha-fetoprotein (AFP) levels in peripheral blood were significantly up-regulated in HCC patients before treatment when compared with healthy people and reduced after TACE combined with AHCS treatment (P < 0.01). In addition, we found that CD4+ cells and NK cells decreased (P < 0.05) and CD8+ cells increased (P < 0.05) in HCC patients when compared with healthy people. After treatment, the CD4+ cells, CD4+/CD8+ ratio, and NK cells were dramatically increased in HCC patients (P < 0.05). In contrast, CD8+ cells were significantly decreased (P < 0.05). TACE combined with AHCS treatment significantly prolonged 1-year survival rate of HCC patients and did not show significant side effects. Taken together, our data indicate that TACE combined with AHCS treatment improves patients' immune system. It is a feasible and effective therapeutic method for HCC patients. PMID- 27259327 TI - Estrogen Receptor Alpha (ERalpha)-Associated Fibroblasts Promote Cell Growth in Prostate Cancer. AB - Estrogen receptor (ER) is expressed in cancer-associated fibroblasts (CAFs) in the stromal compartment of cancerous prostate. However, the effect of ERalpha in CAF cells on prostate cancer (PCa) cell growth remains unclear. We used lentiviral transduction to stably express ERalpha in CAF cells isolated from transgenic adenocarcinoma of the mouse prostate model. MTT and 3D colony formation assays demonstrated that conditioned medium from ERalpha-expressing CAF cells (CAF-ERalpha+) promoted cell proliferation and colony growth of various PCa cell lines, such as PC3, LNCaP, 22RV1, and C4-2. We further confirmed the in vitro data by orthotopically co-implanting 22RV1, transfected with firefly luciferase, and CAF-ERalpha+ cells in vivo using mouse model. Mice co-implanted with CAF-ERalpha+ exhibited stronger luciferase signals and bigger tumor size compared to animals co-implanted with CAF that do not express ER. Our results demonstrate that ER expressed in CAF might play a pro-proliferative role in PCa. PMID- 27259328 TI - Shorter EGFR Dinucleotide Repeat Length Predicts Better Response of Patients with Advanced Non-small Cell Lung Cancer to EGFR Tyrosine Kinase Inhibitor. AB - The purpose of this study is to evaluate the association between intron 1 CA repeat polymorphisms of the epidermal growth factor receptor gene (EGFR) and the clinical outcome of Chinese patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). We genotyped the intron 1 CA-repeat genetic polymorphisms of EGFR in 84 Chinese patients with NSCLC. The relationship between the length of the CA repeats and EGFR mutations in exons 18-21 in the 84 patients was elucidated. We then analyzed the association between the length of the CA repeats and the clinical outcome of EGFR TKI-treated patients with NSCLC. EGFR mutations in exon 19 were significantly associated with shorter CA repeats. Patients with shorter CA repeats had a significantly longer progression-free survival with EGFR-TKI treatment than those with longer CA repeats. Our results suggest that shorter CA repeats in intron 1 of EGFR are associated with EGFR mutations and the clinical outcomes of TKI treated patients with NSCLC. PMID- 27259329 TI - Distribution of EGFR Mutations in 10,607 Russian Patients with Lung Cancer. AB - INTRODUCTION: This study was aimed to evaluate distribution of epidermal growth factor receptor (EGFR) mutations in a large series of Russian lung cancer (LC) patients. METHODS: 10,607 LC samples were considered for EGFR analysis; EGFR status was successfully determined in 10,426 cases (98.3 %), indicating relatively low failure rate. RESULTS: EGFR mutations (ex19del and L858R) were detected in 1759/8716 (20.2 %) adenocarcinomas, 28/669 (4.2 %) squamous cell carcinomas (SCC) and 8/119 (6.7 %) large cell carcinomas. The occurrence of EGFR mutations in adenocarcinomas gradually increased with age, being attributed mainly to the increment of the L858R frequency in non-smokers (patients aged 18 30 years: 1/27 (3.7 %); 31-40 years: 5/98 (5.1 %); 41-50 years: 18/276 (6.5 %); 51-60 years: 102/944 (10.8 %); 61-70 years: 138/1011 (13.7 %); 71-80 years: 85/496 (17.1 %); 81-100 years: 5/27 (18.5 %); p < 0.0001). The EGFR mutation was detected in 804/2107 (38.2 %) non-smoking women versus 125/806 (15.5 %) non smoking men (p < 0.0001), while the corresponding figures for smokers were 60/273 (22.0 %) versus 147/2214 (6.6 %) (p < 0.0001). The obtained gender-related data differ from the estimates obtained in Asian studies; they indicate that increased prevalence of EGFR mutations in white females may not be entirely attributed to the low prevalence of smoking, but is likely to be related to gender factors per se. CONCLUSION: Biological causes of distinct age- and gender-related distribution of EGFR mutations in LC deserve further investigation. PMID- 27259331 TI - Immunotherapy of Colorectal Cancer. AB - It is known that the immune response, reflected by high T cell infiltrates in primary tumors and metastases, influences the clinical course of colorectal cancer (CRC). Therefore, immunotherapy concepts have been adapted from other tumor entities, which typically rely on the activation of T cells in the tumor microenvironment (e.g. blockade of the immune checkpoint molecules PD-1 and CTLA 4). However, most of the strategies using the approved checkpoint inhibitors and/or combination strategies have more or less failed to produce impressive results in early phase trials in CRC. Therefore, a number of novel targets for checkpoint inhibition are currently in early phase clinical testing (TIM-3, Lag 3, OX40, GITR, 4-1BB, CD40, CD70). A simple activation of infiltrating T cells will not, however, lead to a meaningful anti-tumor response without modulating the environmental factors in CRC. Thus, it is absolutely necessary to improve our understanding of the complex regulation of the tumor microenvironment in CRC to design individual combination treatments leading to effective immune control. PMID- 27259330 TI - Transcriptomic Segregation of Human Autoantigens Useful for the Diagnosis of Autoimmune Diseases. AB - The measurement of autoantibodies in the clinical care of autoimmune patients allows for diagnosis, monitoring, and even disease prediction. Despite their clinical utility, the functional significance of autoantibody target proteins in many autoimmune diseases remains unclear. Here we present a comprehensive review of 52 autoantigens commonly employed for the serological diagnosis of 24 autoimmune diseases. We discuss their function, whether they have extracellular exposed epitopes, and whether antibodies to these proteins are known to be pathogenic. Transcriptomics (RNA-Seq) datasets were mined to display messenger RNA (mRNA) expression of the autoantigens across 32 tissues and organs. This analysis revealed that autoantigens cluster into one of three groups: expression in the tissue most strongly affected in the disease (Group I), ubiquitous expression with enrichment in immune tissues (Group II), or expression in other tissues not typically associated with the clinical presentation (Group III). Clustering demonstrated that the autoantigens within Group I were often proteins containing extracellular epitopes, many of which are targets of pathogenic autoantibodies. Group II autoantigens were targets for several rheumatological diseases, including Sjogren syndrome, systemic lupus erythematosus, myositis, and systemic sclerosis, and were ubiquitously expressed with enrichment in immune rich tissues. This raises the possibility that immune cells in Group II disorders may be the source of autoimmunization and/or targets of immune cell responses. Since tissues showing enriched autoantigen gene expression may contribute to the development of autoantibodies and subsequent autoimmunity, the emergent patterns arising from the autoantigen transcriptomic profiles may provide a new heuristic framework to deconvolute these complex disorders. PMID- 27259333 TI - The antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina: an overview. AB - Spirulina is a species of filamentous cyanobacteria that has long been used as a food supplement. In particular, Spirulina platensis and Spirulina maxima are the most important. Thanks to a high protein and vitamin content, Spirulina is used as a nutraceutical food supplement, although its other potential health benefits have attracted much attention. Oxidative stress and dysfunctional immunity cause many diseases in humans, including atherosclerosis, cardiac hypertrophy, heart failure, and hypertension. Thus, the antioxidant, immunomodulatory, and anti inflammatory activities of these microalgae may play an important role in human health. Here, we discuss the antioxidant, immunomodulatory, and anti-inflammatory activities of Spirulina in both animals and humans, along with the underlying mechanisms. In addition, its commercial and regulatory status in different countries is discussed as well. Spirulina activates cellular antioxidant enzymes, inhibits lipid peroxidation and DNA damage, scavenges free radicals, and increases the activity of superoxide dismutase and catalase. Notably, there appears to be a threshold level above which Spirulina will taper off the antioxidant activity. Clinical trials show that Spirulina prevents skeletal muscle damage under conditions of exercise-induced oxidative stress and can stimulate the production of antibodies and up- or downregulate the expression of cytokine-encoding genes to induce immunomodulatory and anti-inflammatory responses. The molecular mechanism(s) by which Spirulina induces these activities is unclear, but phycocyanin and beta-carotene are important molecules. Moreover, Spirulina effectively regulates the ERK1/2, JNK, p38, and IkappaB pathways. This review provides new insight into the potential therapeutic applications of Spirulina and may provide new ideas for future studies. PMID- 27259332 TI - [Rare syndromes in intensive care medicine : Presentation of two cases]. AB - This article presents two cases of young women with spontaneous life-threatening bleeding events. Both had a history of gastrointestinal rupture or arterial dissection. Based on their medical history and genetic testing, Ehlers-Danlos syndrome (EDS) IV (vascular type) was diagnosed. In this very rare disorder which accounts for only 5 % of all EDS cases, fibroblasts synthesize reduced and abnormal procollagen type III. This is caused by mutations in the COL3A1 gene coding for type III procollagen. Life expectancy in these patients is significantly reduced. In many cases spontaneous arterial ruptures or dissections and organ ruptures are the first manifestations of this disease. More than 80 % of patients with EDS IV suffer from a severe complication before 40 years of age. Treatment options are very limited. Most important is to avoid invasive procedures (open surgery as well as endovascular interventions) because of its high morbidity and mortality. Celiprolol, a cardioselective beta-blocker, seems to have a beneficial effect by reducing the incidence of vascular complications. PMID- 27259334 TI - 18F-FDG PET/CT and primary hepatic MALT: a case series. AB - Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare disease and its glucidic metabolic behavior is not clear. We retrospectively analyzed five patients with histological diagnosis of primary hepatic MALT lymphoma who underwent twelve 18F-FDG PET/CT. All staging 18F-FDG PET/CT were positive showing 18F-FDG uptake (average SUVmax was 5.62 +/- 1.6) at the corresponding liver lesion. 18F-FDG PET/CT also was useful in evaluating the complete metabolic response after chemotherapy in three patients and radiotherapy in two. Besides, in one patient 18F-FDG PET/CT detected disease relapse during follow-up. Despite the low number of patients, our case series shows the 18F-FDG avidity of hepatic MALT and the possible role of 18F-FDG PET/CT in the management of these patients, both for staging, treatment response evaluation and restaging. Further studies are needed to confirm our results. PMID- 27259335 TI - Emerging stool-based and blood-based non-invasive DNA tests for colorectal cancer screening: the importance of cancer prevention in addition to cancer detection. AB - Colorectal cancer (CRC) screening can be undertaken utilizing a variety of distinct approaches, which provides both opportunities and confusion. Traditionally, there has often been a trade-off between the degree of invasiveness of a screening test and its ability to prevent cancer, with fecal occult blood testing (FOBT) and optical colonoscopy (OC) at each end of the spectrum. CT colonography (CTC), although currently underutilized for CRC screening, represents an exception since it is only minimally invasive, yet provides accurate evaluation for advanced adenomas. More recently, the FDA approved a multi-target stool DNA test (Cologuard) and a blood-based test (Epi proColon) for average-risk CRC screening. This commentary will provide an overview of these two new non-invasive tests, including the clinical indications, mechanism of action, and diagnostic performance. Relevance to radiology practice, including a comparison with CTC, will also be discussed. PMID- 27259337 TI - Erratum to: Percutaneous biopsy facilitates modern treatment of renal masses. PMID- 27259336 TI - Omental cake. PMID- 27259338 TI - Altered breathing mechanics and ventilatory response during exercise in children born extremely preterm. AB - BACKGROUND: Extreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This study examined respiratory mechanics and ventilatory response during exercise in a large cohort of children born extremely preterm (EP). METHODS: This cohort study included children 8-12 years of age who were born EP (<=28 weeks gestation) between 1997 and 2004 and treated in a large regionalised neonatal intensive care unit in western Canada. EP children were divided into no/mild bronchopulmonary dysplasia (BPD) (ie, supplementary oxygen or ventilation ceased before 36 weeks gestational age; n=53) and moderate/severe BPD (ie, continued supplementary oxygen or ventilation at 36 weeks gestational age; n=50). Age-matched control children (n=65) were born at full term. All children attempted lung function and cardiopulmonary exercise testing measurements. RESULTS: Compared with control children, EP children had lower airway flows and diffusion capacity but preserved total lung capacity. Children with moderate/severe BPD had evidence of gas trapping relative to other groups. The mean difference in exercise capacity (as measured by oxygen uptake (VO2)% predicted) in children with moderate/severe BPD was -18+/-5% and -14+/-5.0% below children with no/mild BPD and control children, respectively. Children with moderate/severe BPD demonstrated a potentiated ventilatory response and greater prevalence of expiratory flow limitation during exercise compared with other groups. Resting lung function did not correlate with exercise capacity. CONCLUSIONS: Expiratory flow limitation and an exaggerated ventilatory response contribute to respiratory limitation to exercise in children born EP with moderate/severe BPD. PMID- 27259339 TI - Economic evaluation of 5-HT3 receptor antagonists in combination with dexamethasone for the prevention of 'overall' nausea and vomiting following highly emetogenic chemotherapy in Chinese adult patients. AB - Background Two pivotal Phase III trials compared the efficacy of palonosetron, ondansetron and granisetron, combined with dexamethasone, for the prevention of nausea and vomiting following highly emetogenic chemotherapy. However, an economic evaluation of these three regimens in the real-world setting of Chinese adult patients has not been determined. Objectives To estimate, from the perspective of the Chinese healthcare system, which of these frequently used strategies consisting of 0.25 mg palonosetron (0.25P), 16 mg ondansetron (Onda), and 3 mg granisetron (Gran), is the most cost-effective option in patients following highly emetogenic chemotherapy. Methods A Markov decision-analytic model was developed. The health and economic outcomes of the three strategies; 0.25P, Onda, and Gran were investigated. The clinical and utility data were taken from published studies. The cost data were calculated according to current local Chinese practices. Sensitivity analyses were performed to determine the impact of uncertainty regarding the results. Results The base-case analysis showed that the 0.25P strategy yielded maximum health benefits compared with the other two strategies. However, the probabilistic sensitivity analysis demonstrated that the Gran strategy was the most cost-effective approach when the willingness-to-pay threshold was not more than US$22,515/quality-adjusted life year. Moreover, palonosetron is not cost-effective in preventing 'overall' nausea and vomiting following highly emetogenic chemotherapy in Chinese patients. Conclusions Our analysis suggests that, compared with palonosetron and ondansetron, 3 mg granisetron may be a cost-effective treatment option in the current Chinese healthcare setting. PMID- 27259340 TI - [New aspects of compression therapy]. AB - In this review article the mechanisms of action of compression therapy are summarized and a survey of materials is presented together with some practical advice how and when these different devices should be applied. Some new experimental findings regarding the optimal dosage (= compression pressure) concerning an improvement of venous hemodynamics and a reduction of oedema are discussed. It is shown, that stiff, non-yielding material applied with adequate pressure provides hemodynamically superior effects compared to elastic material and that relatively low pressures reduce oedema. Compression over the calf is more important to increase the calf pump function compared to graduated compression. In patients with mixed, arterial-venous ulcers and an ABPI over 0.6 inelastic bandages not exceeding a sub-bandage pressure of 40 mmHg may increase the arterial flow and improve venous pumping function. PMID- 27259341 TI - Hypertrophic Cardiomyopathy in a Monozygotic Twin Pair: Similarly Different. PMID- 27259342 TI - The need for supplemental breast cancer screening modalities: a perspective of population-based breast cancer screening programs in Japan. AB - PURPOSE: This article discusses possible supplemental breast cancer screening modalities for younger women with dense breasts from a perspective of population based breast cancer screening program in Japan. CONCLUSION: Supplemental breast cancer screening modalities have been proposed to increase the sensitivity and detection rates of early stage breast cancer in women with dense breasts; however, there are no global guidelines that recommend the use of supplemental breast cancer screening modalities in such women. Also, no criterion standard exists for breast density assessment. Based on the current situation of breast imaging in Japan, the possible supplemental breast cancer screening modalities are ultrasonography, digital breast tomosynthesis, and breast magnetic resonance imaging. An appropriate population-based breast cancer screening program based on the balance between cost and benefit should be a high priority. Further research based on evidence-based medicine is encouraged. It is very important that the ethnicity, workforce, workflow, and resources for breast cancer screening in each country should be considered when considering supplemental breast cancer screening modalities for women with dense breasts. PMID- 27259343 TI - Measurement characteristics for two health-related quality of life measures in older adults: The SF-36 and the CDC Healthy Days items. AB - BACKGROUND: The Short Form Health Survey (SF-36) and the Centers for Disease Control and Prevention (CDC) Healthy Days items are well known measures of health related quality of life. The validity of the SF-36 for older adults and those with disabilities has been questioned. OBJECTIVE: Assess the extent to which the SF-36 and the Centers for Disease Control and Prevention (CDC) Healthy Days items measure the same aspects of health; whether the SF-36 and the CDC unhealthy days items are invariant across gender, functional status, or the presence of chronic health conditions of older adults; and whether each of the SF-36's eight subscales is independently associated with the CDC Healthy Days items. METHODS: We analyzed data from 66,269 adult Medicare advantage members age 65 and older. We used confirmatory factor analyses and regression modeling to test associations between the CDC Healthy Days items and subscales of the SF-36. RESULTS: The CDC Healthy Days items were associated with the SF-36 global measures of physical and mental health. The CDC physically unhealthy days item was associated with the SF 36 subscales for bodily pain, physical role limitations, and general health, while the CDC mentally unhealthy days item was associated with the SF-36 subscales for mental health, emotional role limitations, vitality and social functioning. The SF-36 physical functioning subscale was not independently associated with either of the CDC Healthy Days items. CONCLUSIONS: The CDC Healthy Days items measure similar domains as the SF-36 but appear to assess HRQOL without regard to limitations in functioning. PMID- 27259346 TI - Lithium attenuates lead induced toxicity on mouse non-adherent bone marrow cells. AB - Lead is a poisonous heavy metal that occurs in all parts of environment and causes serious health problems in humans. The aim of the present study was to investigate the possible protective effect of lithium against lead nitrate induced toxicity in non-adherent bone marrow stem cells. Trypan blue and MTT assays represented that exposure of the cells to different concentrations of lead nitrate decreased viability in a dose dependent manner, whereas, pretreatment of the cells with lithium protected the cells against lead toxicity. Lead reduced the number and differentiation status of bone marrow-derived precursors when cultured in the presence of colony stimulating factor (CSF), while the effect was attenuated by lithium. The cells treated with lead nitrate exhibited cell shrinkage, DNA fragmentation, anion superoxide production, but lithium prevented lead action. Moreover, apoptotic indexes such as PARP cleavage and release of HMGB1 induced by lead, were protected by lithium, suggesting anti-apoptotic effect of lithium. Immunoblot analysis of histone H3K9 acetylation indicated that lithium overcame lead effect on acetylation. In conclusion, lithium efficiently reduces lead toxicity suggesting new insight into lithium action which may contribute to increased cell survival. It also provides a potentially new therapeutic strategy for lithium and a cost-effective approach to minimize destructive effects of lead on bone marrow stem cells. PMID- 27259345 TI - Oleuropein ameliorates arsenic induced oxidative stress in mice. AB - The objective of this study is to investigate the potential preventive effect of oleuropein in an experimental arsenic toxicity in mice. For this purpose, mice were exposed to 5mg/kg/day sodium arsenite (NaAsO2) in drinking water and treated with 30mg/kg/day oleuropein for 15 days. At the end of the experiment, animals were sacrificed and selected organs were processed for biochemical and histopahtological investigations. Blood, liver, kidney and brain malondialdehyde (MDA) and nitric oxide (NO) levels were determined by colorimetric methods. Protein carbonyl content is measured by a commercial kit. Liver morphology and immunoreactivity for inducible NOS (iNOS) and endothelial NOS (eNOS) was evaluated microscopically. Level of NO was determined to decrease in blood and tissues whereas MDA increased in arsenic given mice. Tissue protein carbonyl content also increased in this group. Immunoreactivity for iNOS and eNOS was noted to increase with arsenic treatment. Oleuropein treatment had significant effects in normalizing the MDA and NO levels as well as protein carbonyl content. Immunohistochemical staining also showed reduction of the expression of iNOS and eNOS in liver. The results indicate that oleuropein ameliorates oxidative tissue damage by scavenging free radicals. PMID- 27259344 TI - Anisotropic cerebral vascular architecture causes orientation dependency in cerebral blood flow and volume measured with dynamic susceptibility contrast magnetic resonance imaging. AB - Measurements of cerebral perfusion using dynamic susceptibility contrast magnetic resonance imaging rely on the assumption of isotropic vascular architecture. However, a considerable fraction of vessels runs in parallel with white matter tracts. Here, we investigate the effects of tissue orientation on dynamic susceptibility contrast magnetic resonance imaging. Tissue orientation was measured using diffusion tensor imaging and dynamic susceptibility contrast was performed with gradient echo planar imaging. Perfusion parameters and the raw dynamic susceptibility contrast signals were correlated with tissue orientation. Additionally, numerical simulations were performed for a range of vascular volumes of both the isotropic vascular bed and anisotropic vessel components, as well as for a range of contrast agent concentrations. The effect of the contrast agent was much larger in white matter tissue perpendicular to the main magnetic field compared to white matter parallel to the main magnetic field. In addition, cerebral blood flow and cerebral blood volume were affected in the same way with angle-dependent variations of up to 130%. Mean transit time and time to maximum of the residual curve exhibited weak orientation dependency of 10%. Numerical simulations agreed with the measured data, showing that one-third of the white matter vascular volume is comprised of vessels running in parallel with the fibre tracts. PMID- 27259347 TI - Evidence of the direct adsorption of mercury in human hair during occupational exposure to mercury vapour. AB - We have found clear evidence of direct adsorption of mercury in human hair after the occupational exposure to mercury vapour. We have performed both longitudinal analysis of human hair by laser ablation ICP-MS and speciation analysis by gas chromatography ICP-MS in single hair strands of 5 individuals which were occupationally exposed to high levels of mercury vapour and showed acute mercury poisoning symptoms. Hair samples, between 3.5 and 11cm long depending on the individual, were taken ca. three months after exposure. Single point laser ablation samples of 50MUm diameter were taken at 1mm intervals starting from the root of the hairs. Sulfur-34 was used as internal standard. The ratio (202)Hg/(34)S showed a distinct pattern of mercury concentration with much lower levels of mercury near the root of the hair and high levels of mercury near the end of the hair. In all cases a big jump in the concentration of mercury in hair occurred at a given distance from the root, between 32 and 42mm depending on the individual, with a high and almost constant concentration of mercury for longer distances to the root. When we took into account the rate of hair growth in humans, 9-15mm/month, the jump in mercury concentration agreed approximately with the dates when the contamination occurred with the new growing hair showing much lower mercury concentration. In some cases the concentration of mercury at the tip of the hair was ca. 1000 times higher than that near the root. Additionally, speciation studies confirmed that mercury in all hair samples was present as inorganic mercury. The only explanation for these results was the direct adsorption of mercury vapour in hair at the time of exposure. PMID- 27259348 TI - Levels of l-ascorbic acid and cadmium in the saphenous vein of patients with coronary artery disease are negatively correlated. AB - BACKGROUND: The aim of this study was the simultaneous determination of levels of cadmium and l-ascorbic Acid (AA) in human saphenous vein (SV) used in coronary artery bypass grafting (CABG) and check whether there is a relationship between these levels. METHODS: Human SV were collected from 40 patients (20 men and 20 women; age, 40-75 years) at the time of routine coronary artery surgical revascularization. The concentration of cadmium in the tissue was determined according to the GF AAS-atomic absorption method. The concentration of AA was assayed in supernatant by FIA method with spectrophotometric detection. RESULTS: AA concentration (mean+/-SD); men: 98,7+/-13,18MUg/g tissue, women: 96,06+/ 11,98MUg/g tissue. Cadmium concentration(mean+/-SD); men: 309+/-103,71ng/g tissue, women: 348,5+/-255,71ng/g tissue. Correlations among concentrations of AA and cadmium were insignificant negative in the group of men (Pearson r=-0,1504, p=0,5269) and in the group women (Pearson r=-0339, p=0144). CONCLUSIONS: Negative correlations among concentrations of AA and cadmium in human SV obtained in our study may indicate a protective effect of this vitamin in relation to toxic cadmium. PMID- 27259349 TI - Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction are reversed by Ocimum gratissimum and gallic acid in Wistar rats. AB - The protective abilities of the chloroform extract of Ocimum gratissimum (COG) and gallic acid against cobalt chloride (CoCl2) - induced cardiac and renal toxicity were evaluated. Rats were exposed to CoCl2 (350ppm) for 7 days, either alone, or in combination with COG (100 and 200mg/kg) or gallic acid (120mg/kg). CoCl2 given alone, caused significant increases (p<0.05) in oxidative stress parameters (hydrogen peroxide, H2O2 and malondialdehyde, MDA) and increased expression of the apoptotic initiator caspase 8 in the heart and kidneys. There was significant reduction (p<0.05) in reduced glutathione (GSH) in cardiac and renal tissues; reduction in superoxide dismutase (SOD) activity in the kidneys and adaptive increases in Glutathione S-transferase (GST) and catalase (CAT). CoCl2 also produced significant reduction (p<0.05) in systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressures. Oral COG and gallic acid treatment significantly reduced (p<0.05) the levels of H2O2 and MDA; with reduced expression of caspase 8 and restoration of GSH levels, GPx, SOD and CAT activities, howbeit, to varying degrees in the heart and kidneys. COG (200mg/kg) was most effective in restoring the blood pressures in the rats to near control levels. CoCl2-induced histopathological lesions including myocardial infarction and inflammation and renal tubular necrosis and inflammation were effectively ameliorated by the treatments administered. This study provides evidence for the protective roles of O. gratissimum and gallic acid by modulation of CoCl2-induced alterations in blood pressure, antioxidant status and pro-apoptotic caspase 8 in Wistar rats. PMID- 27259350 TI - Metal bioaccumulation in edible target tissues of mullet (Mugil liza) from a tropical bay in Southeastern Brazil. AB - The present study aimed to investigate metal bioaccumulation in mullet (M. liza) from a tropical bay located in Southeastern Brazil, comparing a previously considered reference site to a known contaminated area of the bay, as well as to conduct human health risk assessments with regard to the consumption of this species. The metal concentrations were compared to the maximum residue level (MRL) in foods established by the different national and international regulatory agencies, and the Provisional Tolerable Daily Intake (PTDI) was determined and compared to reference values. Chromium (Cr), Zinc (Zn), Copper (Cu), Manganese (Mn), Nickel (Ni), Cadmium (Cd) and Lead (Pb) concentrations were determined in the gills, muscle and liver of 28 mullet by ICP-MS after acid digestion. Certain metals exceeded MRL guidelines established by different regulatory agencies, indicating human health risks associated to these metals. PTDI values, however, did not exceed corresponding metal values proposed by the World Health Organization. The metal concentrations found in the mullet samples indicate that the previously considered reference site is now showing signs of anthropogenic contamination. PMID- 27259351 TI - ICPMS analysis of proteins separated by Native-PAGE: Evaluation of metaloprotein profiles in human synovial fluid with acute and chronic arthritis. AB - The role of trace elements bound to proteins in the etiology and pathogenesis of rheumatoid arthritis (RA) remains unclear. In this sense, the identification and detection of metalloproteins has a strong and growing interest. Metalloprotein studies are currently carried out by polyacrylamide gel electrophoresis (PAGE) associated to inductively coupled plasma mass spectrometry (ICPMS), and despite that complete information can be obtained for metals such as Fe, Cu and Zn, difficulties due to poor sensitivity for other trace elements such as Sn, As, etc, are currently faced. In the present work, a simple and fast method for the determination of trace metals bound to synovial fluid (SF) proteins was optimized. Proteins from SF (long and short-term RA) were separated in ten fractions by native PAGE, then dissolved in nitric acid and peroxide hydrogen, and analyzed by ICPMS. Fifteen metals were determined in each separated protein fraction (band). Adequate calibration of proteins molecular weight allowed stablishing which protein type were bound to different metals. PMID- 27259352 TI - Impact of dialyzer membrane flux on metal clearance in hemodialysis patients. AB - Deficiency of essential trace elements (such as Cu or Zn) and accumulation of potentially toxic trace elements (as Cd or Pb) are both known to have adverse effects in hemodialysis (HD) patients. Up to our knowledge, no studies about the permeability of low and high flux polysulfone membranes on metal ions during hemodialysis are available. Therefore, the aim of the present study was to address this issue. Forty one hemodialysis patients (19 were using high flux polysulfone membrane while the remaining were using low flux one) participated in the study. Blood levels of Cu, Zn, Cd and Pb were determined by graphite furnace atomic absorption spectrometry among HD patients, before and after dialysis session, as well as among matched 40 healthy persons. Blood concentrations of Cu and Zn in the whole hemodialysis group was significantly lower than those of the healthy control group, on the other hand the toxic metals (Cd and Pb) levels were observed to be significantly higher among HD patients compared to the normal persons. Among the hemodialysis group, there were no significant differences between the low and high flux dialyzer groups in terms of pre-dialysis blood levels of Cu, Zn, Cd and Pb. In addition, significantly decreased levels of all metal ions were observed after dialysis sessions using either low or high flux membranes. An exception was Pb which did not show any difference between pre dialysis and post-dialysis values in the low flux groupIn conclusion Zn and Cu deficiencies should be considered in the treatment of these patients. High flux membranes are more efficient than low flux ones in removing excess Cd and Pb. Therefore, when high flux membranes are used, chelation therapy might not be required for Cd and Pb overload. PMID- 27259353 TI - Incidence of thyroid diseases in Zhejiang Province, China, after 15 years of salt iodization. AB - Thyroid diseases(TD) can be induced by either deficient or excessive iodine intake. Universal Salt Iodization(USI) program has been implemented in China since 1995, to prevent iodine deficiency disorders (IDD). To evaluate the current conditions of TD and the role of USI, a multi-stage stratified random sampling scheme was used to perform a cross-sectional survey on the incidence of TD among participants in 6600 households in Zhejiang Province, a coastal area in China. Iodine nutrition status of the population was assessed by dietary iodine intake recall and urinary iodine concentration (UIC) of the participants, and TD were diagnosed by thyroid ultrasonography for 15122 participants and for 5873 participants by serum criteria for thyroid function(fT3, fT4, TSH, TRAb, TgAb, TPOAb; see Introduction for abbreviations). The median UIC of the surveyed population was 163MUg iodine/L. From the participants 23.2% had UIC<100MUg/L which is moderately iodine-deficient according to WHO classification. Diffuse goiter was present in 2.3% of the population and thyroid nodule in 20.9%. The incidence of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, Graves' disease and chronic lymphocytic thyroiditis was 0.5%, 0.6%, 0.6%, 7.8%, 0.2% and 0.3%, respectively. The proportion of several TD for participants with non-iodized salt intake was higher than that for participants with iodized salt intake. PMID- 27259354 TI - Effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients: Double blind, randomized clinical trial: Chromium, glucose homeostasis and anthropometry. AB - OBJECTIVE: To evaluate the effect of chromium supplementation on the glucose homeostasis and anthropometry of type 2 diabetic patients. MATERIAL AND METHODS: Fifty-six individuals with type 2 Diabetes were randomized on a double blind clinical trial into three groups: placebo (NC0), 50MUg (NC50) and 200MUg (NC200) of chromium nicotinate. Glucose homeostasis, anthropometry and physical activity intensity were evaluated at the beginning, at day 45 and at day 90. Energy intake was evaluated at the beginning, between the beginning and 45 days, and between days 45 and 90 of the study. RESULTS: There were no differences within or between groups for HOMA-IR, waist circumference, body fat percentage, lean body mass percentage and total energy intake during the trial. There was an increase of the HOMA-beta in group NC0 (p=0.0349) and a decrease of 1.08kg in group NC50 (p=0.0048) at 90 days. The relation between body mass index, body fat percentage and insulin sensitivity did not change in the placebo and supplemented groups (p>0.05). In the effect of the intervention, for each 1cm increase in waist circumference there was an increase of 1.90+/-0.63 in HOMA-IR (p=0.0087) and 16.31+/-5.27% in HOMA-beta (p=0.0073) in group NC200. No difference was seen in the intensity of physical activity within the groups and in the comparison between the supplemented groups (NC50 and NC200) and placebo (NC0) at 90 days. There was an increase in energy expenditure in physical activity at 90days (p=0.0371) of intervention in the group subjects NC50. As for total energy intake, there were no differences within or between the groups during the study. CONCLUSION: 50MUg and 200MUg supplementation with chromium nicotinate for 90days did not promote improvements in glucose homeostasis and anthropometry in individuals with type 2 diabetes mellitus. PMID- 27259356 TI - Validity of the copper/zinc ratio as a diagnostic marker for taste disorders associated with zinc deficiency. AB - Although zinc (Zn) deficiency is often suspected in patients with taste disorders, it may be difficult to diagnose Zn deficiency, especially in patients without any clear risk factors. Accordingly, the aim of the present study was to detect possible markers for taste disorders or zinc deficiency. To achieve this aim, we analyzed data obtained from 122 Japanese men who were not using medicines and had no diseases requiring treatment. We evaluated the following factors: awareness of dysgeusia; salty taste recognition threshold (SRT); the serum concentrations of Zn, copper (Cu), iron, alkaline phosphatase, and albumin; and the Cu/Zn ratio. The serum Cu/Zn ratio was positively correlated with the both the SRT and the awareness of dysgeusia. The serum Zn concentration was not correlated with the SRT or the awareness of dysgeusia in univariate analyses. However, in multivariate logistic regression, the serum Zn concentration was associated with the awareness of dysgeusia. In conclusion, the serum Cu/Zn ratio is a good diagnostic marker for taste disorders and the value of 1.1 may be a threshold level for detecting taste disorders. PMID- 27259355 TI - Boron influences immune and antioxidant responses by modulating hepatic superoxide dismutase activity under calcium deficit abiotic stress in Wistar rats. AB - The influence of Boron (B) supplementation on immune and antioxidant status of rats with or without abiotic stress induced by dietary calcium (Ca) restriction was studied in a feeding trial of 90 days. Wistar strain rats (3-4 wk age, n=84) were divided into 7 dietary groups (4 replicates of 3 each) viz., normal-calcium (100%) basal diet alone (NC, control) or supplemented with B at 5 (NCB-5), 10 (NCB-10), 20 (NCB-20) and 40ppm (NCB-40) levels; low-calcium (50%) basal diet alone (LC) or supplemented with 40ppm B (LCB-40). After 75 days of experimental feeding, rats were challenged with intraperitoneal injection of sheep RBCs to assess their humoral immunity. At the end of the trial, cell-mediated immunity was assessed as foot pad reaction to sheep RBCs injected into the hind leg paws. Eight rats from each group were sacrificed to collect blood for estimation of minerals and total antioxidant activity, and liver for superoxide dismutase gene expression analysis. Supplementation of graded levels of B (5, 10, 20 and 40ppm) as borax in NC diets significantly increased (P<0.01) the footpad thickness and serum total antioxidant activity, hepatic expression levels of both Cu-Zn SOD (SOD1) and Mn-SOD (SOD2) mRNAs. The erythrocytic SOD activity and humoral response did not differ significantly among the dietary groups. In Ca restricted groups, humoral immune response was significantly decreased (P<0.01) compared to control but increased (P<0.05) with 40ppm B supplementation. Serum levels of copper (Cu) and zinc (Zn) remained similar among the dietary groups, while the manganese (Mn) content was significantly decreased (P<0.01) with increased levels of dietary B. In conclusion, B supplementation increased the hepatic mRNA expression levels of both SOD isoenzymes, thereby improving the immune and antioxidant status. PMID- 27259357 TI - The influence of manganese treatment on the distribution of metal elements in rats and the protection by sodium para-amino salicylic acid. AB - Manganese (Mn) overexposure induced neurological damages, which could be potentially protected by sodium para-aminosalicylic acid (PAS-Na). In this study, we systematically detected the changes of divalent metal elements in most of the organs and analyzed the distribution of the metals in Mn-exposed rats and the protection by PAS-Na. Sprague Dawley (SD) rats received intraperitoneal injections of 15mg/kg MnCl2.4H2O (5d/week for 3 weeks), followed by subcutaneous (back) injections of PAS-Na (100 and 200mg/kg, everyday for 5 weeks). The concentrations of Mn and other metal elements [Iron (Fe), Copper (Cu), Zinc (Zn), Magnesium (Mg), Calcium (Ca)] in major organs (liver, spleen, kidney, thighbone and iliac bone, cerebral cortex, hippocampus and testes) and blood by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that Mn overexposure significantly increased Mn in most organs, Fe and Zn in liver, Fe and Mg in blood; however decreased Fe, Cu, Zn, Mg and Ca in cortex, Cu and Zn in kidney, Cu and Mg in iliac bone, and Zn in blood. In contrast, PAS-Na treatment restored most changes particularly in cortex. In conclusion, excessive Mn exposure disturbed the balance of other metal elements but PAS-Na post-treatments could restore these alterations. PMID- 27259359 TI - Technical Aspects and Benefits of Experimental Mouse Lung Transplantation. AB - In recent years, the number of lung transplantations performed as the last option for many respiratory diseases has grown considerably, both in adults and children. However, the causes for the relatively short survival of lungs compared to other organ transplants still need to be studied. Techniques have improved since the 1950s when experimental lung transplantation began, and the different animal species used now include rodents. The advantage of using these small species is that the surgical model has been expanded and standardized, and different respiratory problems can be studied. In this review we examine the different technical strategies used in experimental transplantation in rats and mice, focusing on surgical techniques and anesthesia and monitoring methods, and highlighting the major contributions of mouse lung transplantation to the field. PMID- 27259358 TI - Resolution of Novel Pancreatic Ductal Adenocarcinoma Subtypes by Global Phosphotyrosine Profiling. AB - Comprehensive characterization of signaling in pancreatic ductal adenocarcinoma (PDAC) promises to enhance our understanding of the molecular aberrations driving this devastating disease, and may identify novel therapeutic targets as well as biomarkers that enable stratification of patients for optimal therapy. Here, we use immunoaffinity-coupled high-resolution mass spectrometry to characterize global tyrosine phosphorylation patterns across two large panels of human PDAC cell lines: the ATCC series (19 cell lines) and TKCC series (17 cell lines). This resulted in the identification and quantification of over 1800 class 1 tyrosine phosphorylation sites and the consistent segregation of both PDAC cell line series into three subtypes with distinct tyrosine phosphorylation profiles. Subtype-selective signaling networks were characterized by identification of subtype-enriched phosphosites together with pathway and network analyses. This revealed that the three subtypes characteristic of the ATCC series were associated with perturbations in signaling networks associated with cell-cell adhesion and epithelial-mesenchyme transition, mRNA metabolism, and receptor tyrosine kinase (RTK) signaling, respectively. Specifically, the third subtype exhibited enhanced tyrosine phosphorylation of multiple RTKs including the EGFR, ERBB3 and MET. Interestingly, a similar RTK-enriched subtype was identified in the TKCC series, and 'classifier' sites for each series identified using Random Forest models were able to predict the subtypes of the alternate series with high accuracy, highlighting the conservation of the three subtypes across the two series. Finally, RTK-enriched cell lines from both series exhibited enhanced sensitivity to the small molecule EGFR inhibitor erlotinib, indicating that their phosphosignature may provide a predictive biomarker for response to this targeted therapy. These studies highlight how resolution of subtype-selective signaling networks can provide a novel taxonomy for particular cancers, and provide insights into PDAC biology that can be exploited for improved patient management. PMID- 27259360 TI - Do COPD treatment guidelines correctly address the treatment of smoking? PMID- 27259361 TI - Combination therapy targeting both cancer stem-like cells and bulk tumor cells for improved efficacy of breast cancer treatment. AB - Many types of tumors are organized in a hierarchy of heterogeneous cell populations. The cancer stem-like cells (CSCs) hypothesis suggests that tumor development and metastasis are driven by a minority population of cells, which are responsible for tumor initiation, growth and recurrences. The inability to efficiently eliminate CSCs during chemotherapy, together with CSCs being highly tumorigenic and invasive, may result in treatment failure due to cancer relapse and metastases. CSCs are emerging as a promising target for the development of translational cancer therapies. Ideal panacea for cancer would kill all malignant cells, including CSCs and bulk tumor cells. Since both chemotherapy and CSCs specific therapy are insufficient to cure cancer, we propose combination therapy with CSCs-targeted agents and chemotherapeutics for improved breast cancer treatment. We generated in vitro mammosphere of 2 breast cancer cell lines, and demonstrated ability of mammospheres to grow and enrich cancer cells with stem like properties, including self-renewal, multilineage differentiation and enrichment of cells expressing breast cancer stem-like cell biomarkers CD44(+)/CD24(-/low). The formation of mammospheres was significantly inhibited by salinomycin, validating its pharmacological role against the cancer stem-like cells. In contrast, paclitaxel showed a minimal effect on the proliferation and growth of breast cancer stem-like cells. While combination therapies of salinomycin with conventional chemotherapy (paclitaxel or lipodox) showed a potential to improve tumor cell killing, different subtypes of breast cancer cells showed different patterns in response to the combination therapies. While optimization of combination therapy is warranted, the design of combination therapy should consider phenotypic attributes of breast cancer types. PMID- 27259362 TI - Identification and characterization of Dichelobacter nodosus serogroup H from ovine footrot in India. AB - A total of 56 foot swabs were collected from inter digital spaces of sheep with footrot lesions were screened for 16 rRNA of Dichelobacter nodosus by PCR. Out of the 56 samples, 38(67.85%) were found to be positive. All the positive samples were subjected to multiplex PCR targeting fimA gene for identification of serogroups of D. nodosus. Serogroup H was found along with serogroup B in 12 (55.26%) samples and with serogroup I in 8 (22.2%) samples. The serogroup H was identified for the first time from the Indian subcontinent. The phylogenetic analysis of the present sequence with the available serogroup H sequences of GenBank revealed to be in close association with the serotype H1. PMID- 27259363 TI - Letter to the Editor. PMID- 27259364 TI - sesC as a genetic marker for easy identification of Staphylococcus epidermidis from other isolates. AB - Staphylococcus epidermidis is one of the major concerns with respect to hospital acquired infections. Therefore, a rapid and easy method to identify at species level S. epidermidis isolates out of a broad range of bacteria is necessary. Based on earlier studies, the sesC gene encoding a S. epidermidis surface protein revealed to be a highly conserved gene in this species. By means of an easy and inexpensive PCR assay, the presence of sesC was checked in 438 clinical staphylococcal isolates. Results showed that sesC is specifically present in all S. epidermidis. In conclusion, the sesC gene can be exploited as a genetic marker in order to distinguish S. epidermidis from other isolates. PMID- 27259365 TI - Tracing the origin of a singular HIV-1 CRF45_cpx clade identified in Brazil. AB - The HIV-1 epidemiology has changed over the past decade toward a marked increase in the circulation of strains previously restricted to local epidemics. Recent molecular epidemiological surveys identified some HIV-1 strains of probable African origin circulating in Brazil, including the Circulating Recombinant Form (CRF) 45_cpx, a complex A1/K/U recombinant that circulates in Central Africa. Here, we characterize partial genomic sequences and reconstruct the evolutionary history of HIV-1 CRF45_cpx-related recombinant samples identified in independent studies carried out with HIV+ individuals in Brazil. The sequences were obtained by overlapping PCR amplifications followed by direct sequencing. Recombination profiles were determined by phylogenetic and bootscaning analyses. The evolutionary history was estimated by a Bayesian coalescent-based method using datasets representing the gag, pol and env gene fragments. Six of the 10 samples isolated in Rio de Janeiro showed a CRF45_cpx-like pattern throughout the sequenced genome. The remaining were classified as second-generation recombinants, showing the mosaic patterns: CRF45_cpx/B/D/F1/U, CRF45_cpx/B/F1/U, CRF45_cpx/B/U and CRF45_cpx/F1. All Brazilian CRF45_cpx sequences, except one, formed a monophyletic clade (CRF45-BR), which seems to be the result of a single introduction event that has spread to the Rio de Janeiro, Sao Paulo and Minas Gerais states and is related to sequences from Argentina, Italy and Belgium. The Bayesian analyses pointed out quite consistent onset dates for CRF45-BR clade (~1984: 1976-1996) in the three gene datasets. These results indicate that the CRF45-BR clade has been circulating in the Southeastern Brazilian region for about 30years, although its presence was not detected until recently due to its very low prevalence. This reinforces the relevance of large-scale molecular surveillance data to identify the emergence of new HIV variants and their impact on local epidemics. PMID- 27259366 TI - Characterization and pathogenicity of a novel mammalian orthoreovirus from wild short-nosed fruit bats. AB - Mammalian orthoreoviruses (MRVs) have a wide range of geographic distribution and have been isolated from humans and various animals. This study describes the isolation, molecular characterization and analysis of pathogenicity of MRV variant B/03 from wild short-nosed fruit bats. Negative stain electron microscopy illustrated that the B/03 strain is a non-enveloped icosahedral virus with a diameter of 70nm. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) migration patterns showed that the B/03 viral genome contains 10 segments in a 3:3:4 arrangement. The isolate belongs to MRV serotype 1 based on S1 gene nucleotide sequence data. BALB/c mice experimentally infected with B/03 virus by intranasal inoculation developed severe respiratory distress with tissue damage and inflammation. Lastly, B/03 virus has an increased transmission risk between bats and humans or animals. PMID- 27259367 TI - Genetic diversity and multiplicity of infection of Plasmodium falciparum isolates from Kolkata, West Bengal, India. AB - The study of genetic diversity of Plasmodium falciparum is necessary to understand the distribution and dynamics of parasite populations. The genetic diversity of P. falciparum merozoite surface protein-1 and 2 has been extensively studied from different parts of world. However, limited data are available from India. This study was aimed to determine the genetic diversity and multiplicity of infection (MOI) of P. falciparum population in Kolkata, West Bengal, India. A total of 80day-zero blood samples from Kolkata were collected during a therapeutic efficacy study in 2008-2009. DNA was extracted; allelic frequency and diversity were investigated by PCR-genotyping method for msp1 and msp2 gene and fragment sizing was done by Bio-Rad Gel-Doc system using Image Lab (version 4.1) software. P. falciparum msp1 and msp2 markers were highly polymorphic with low allele frequencies. In Kolkata, 27 msp1 different genotypes (including 11of K1, 6 of MAD20 and 10 of Ro33 allelic families) and 30 different msp2 genotypes (of which 17 and 13 belonged to the FC27 and 3D7 allelic families, respectively) were recorded. The majority of these genotypes occurred at a frequency below 10%. The mean MOI for msp1 and msp2 gene were 2.05 and 3.72, respectively. The P. falciparum population of Kolkata was genetically diverse. As the frequencies of most of the msp1 and msp2 alleles were low, the probability of new infection with genotype identical to that in pretreatment infection was very rare. This information will serve as baseline data for evaluation of malaria control interventions as well as for monitoring the parasite population structure. PMID- 27259370 TI - Cinnamaldehyde and its derivatives, a novel class of antifungal agents. AB - The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal. PMID- 27259371 TI - The adaptor molecule Trif contributes to murine host defense during Leptospiral infection. AB - Leptospirosis is a zoonotic disease and is caused by pathogenic species of the Leptospira genus, including Leptospira interrogans (L. interrogans). Humans, domestic and wild animals are susceptible to acute or chronic infection. The innate immune response is a critical defense mechanism against Leptospira interrogans, and has been investigated in mouse models. Murine Toll-like receptors (TLRs) have been shown to be key factors in sensing and responding to L. interrogans infection. Specifically, TLR2, TLR4 and the TLR adaptor molecule MyD88 are essential for host defense against L. interrogans; however, the role of the TLR adaptor molecule TIR-domain-containing adaptor-inducing interferon beta (TRIF) in the response to L. interrogans has not been previously determined. In the present study, TRIF was found to play an important role during leptospiral infection. Following challenge with L. interrogans, Trif(-/-) mice exhibited delayed weight gain compared to wild-type mice. Moreover, Trif(-/-) mice exhibited an increase in L. interrogans burden in the kidneys, lungs, and blood at early time points (less than 7days post infection). Multiple components of the innate immune responses were dampened in response to leptospiral infection including transcription and production of cytokines, and the humoral response, which suggested that TRIF contributes to expression and production of cytokines important for the host defense against L. interrogans. PMID- 27259369 TI - CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion. AB - Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/ ) mice after ischemia reperfusion injury. Wild-type animals had minimal self renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. PMID- 27259368 TI - Reduced risk of myocardial infarct and revascularization following coronary artery bypass grafting compared with percutaneous coronary intervention in patients with chronic kidney disease. AB - Coronary atherosclerotic disease is highly prevalent in chronic kidney disease (CKD). Although revascularization improves outcomes, procedural risks are increased in CKD, and unbiased data comparing coronary artery bypass grafting (CABG) and percutaneous intervention (PCI) in CKD are sparse. To compare outcomes of CABG and PCI in stage 3 to 5 CKD, we identified randomized trials comparing these procedures. Investigators were contacted to obtain individual, patient level data. Ten of 27 trials meeting inclusion criteria provided data. These trials enrolled 3993 patients encompassing 526 patients with stage 3 to 5 CKD of whom 137 were stage 3b-5 CKD. Among individuals with stage 3 to 5 CKD, mortality through 5 years was not different after CABG compared with PCI (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.67-1.46) or stage 3b-5 CKD (HR 1.29, CI 0.68 2.46). However, CKD modified the impact on survival free of myocardial infarction: it was not different between CABG and PCI for individuals with preserved kidney function (HR 0.97, CI 0.80-1.17), but was significantly lower after CABG in stage 3-5 CKD (HR 0.49, CI 0.29-0.82) and stage 3b-5 CKD (HR 0.23, CI 0.09-0.58). Repeat revascularization was reduced after CABG compared with PCI regardless, of baseline kidney function. Results were limited by unavailability of data from several trials and paucity of enrolled patients with stage 4-5 CKD. Thus, our patient-level meta-analysis of individuals with CKD randomized to CABG versus PCI suggests that CABG significantly reduces the risk of subsequent myocardial infarction and revascularization without affecting survival in these patients. PMID- 27259373 TI - At-risk adolescents as experts in a new requirements elicitation procedure for the development of a smart phone psychoeducational trauma-informed care application. AB - BACKGROUND/PURPOSE: Adolescents from urban, socioeconomically disadvantaged communities of color encounter high rates of adverse childhood experiences. To address the resulting multidimensional problems, we developed an innovative approach, Experiential Participatory and Interactive Knowledge Elicitation (EPIKE), using remote experiential needs elicitation methods to generate design and content requirements for a mobile health (mHealth) psychoeducational intervention. METHODS: At a community-based organization in a northeastern city, the research team developed EPIKE by incorporating elicitation of input on the graphics and conducting remotely recorded experiential meetings and iterative reviews of the design to produce an mHealth smartphone story application (app) prototype for the participants to critique. The 22 participants were 13- to 17 year-olds, predominantly African American and female, from underresourced communities. RESULTS: The four goals of the design process were attained: 1) story development from participant input; 2) needs-elicitation that reflected the patient-centered care approach; 3) interactive story game creation that accommodates the participants' emotional and cognitive developmental needs; 4) development of a game that adolescents can relate to and that which matches their comfort levels of emotional intensity. CONCLUSIONS: The EPIKE approach can be used successfully to identify the needs of adolescents across the digital divide to inform the design and development of mHealth apps. PMID- 27259374 TI - Development and deposition of resilin in energy stores for locust jumping. AB - Locusts jump by using a catapult mechanism in which energy produced by slow contractions of the extensor tibiae muscles of the hind legs is stored in distortions of the exoskeleton, most notably (1) the two semi-lunar processes at each knee joint and (2) the tendons of the extensor muscles themselves. The energy is then suddenly released from these stores to power the rapid, propulsive movements of the hind legs. The reliance on the mechanical storage of energy is likely to impact on jumping because growth occurs by a series of five moults, at each of which the exoskeleton is replaced by a new one. All developmental stages (instars) nevertheless jump as a means of forward locomotion, or as an escape movement. Here, I show that in each instar, resilin is added to the semi-lunar processes and to the core of the extensor tendons so that their thickness increases. As the next moult approaches, a new exoskeleton forms within the old one, with resilin already present in the new semi-lunar processes. The old exoskeleton, the tendons and their resilin are discarded at moulting. The resilin of the semi-lunar processes and tendons of the new instar is initially thin, but a similar pattern of deposition results in an increase of their thickness. In adults, resilin continues to be deposited so that at 4 weeks old the thickness in the semi-lunar processes has increased fourfold. These changes in the energy stores accompany changes in jumping ability and performance during each moulting cycle. PMID- 27259375 TI - Disentangling the visual cues used by a jumping spider to locate its microhabitat. AB - Many arthropod species have evolved to thrive only on the leaves of a particular species of plant, which they must be capable of finding in order to survive accidental displacement, developmental transitions or the changing of the seasons. A number of studies have tested whether such species select leaves to land or oviposit on based on their color, shape or size. Unfortunately, many studies did not control for correlates of these characters, such as the brightness of different colors, the areas of different shapes, and the level of ambient illumination in the vicinity of different sizes of leaves. In the present study, we tested for leaf color, shape and size preferences in a leaf-dwelling jumping spider (Lyssomanes viridis) with known summer and winter host plants, while controlling for these correlates. First, color preferences were tested outdoors under the natural illumination of their forest habitat. Lyssomanes viridis did not prefer to perch on a green substrate compared with various shades of gray, but did prefer the second darkest shade of gray we presented them with. Of the green and gray substrates, this shade of gray's integrated photon flux (350-700 nm), viewed from below, i.e. the spider's perspective in the arena, was the most similar to that of real leaves. This relationship also held when we weighted the transmitted photon flux by the jumping spiders' green photopigment spectral sensitivity. Spiders did not prefer the star-like leaf shape of their summer host plant, Liquidambar styraciflua, to a green circle of the same area. When given a choice between a L. styraciflua leaf-shaped stimulus that was half the area of an otherwise identical alternative, spiders preferred the larger stimulus. However, placing a neutral density filter over the side of the experimental arena with the smaller stimulus abolished this preference, with spiders then being more likely to choose the side of the arena with the smaller stimulus. In conclusion, L. viridis appears to use ambient illumination and possibly perceived leaf brightness but not leaf shape or color to locate its microhabitat. This calls for a careful re-examination of which visual cues a variety of arthropods are actually attending to when they search for their preferred host species or microhabitat. PMID- 27259372 TI - Characterization of the gene encoding component C3 of the complement system from the spider Loxosceles laeta venom glands: Phylogenetic implications. AB - A transcriptome analysis of the venom glands of the spider Loxosceles laeta, performed by our group, in a previous study (Fernandes-Pedrosa et al., 2008), revealed a transcript with a sequence similar to the human complement component C3. Here we present the analysis of this transcript. cDNA fragments encoding the C3 homologue (Lox-C3) were amplified from total RNA isolated from the venom glands of L. laeta by RACE-PCR. Lox-C3 is a 5178 bps cDNA sequence encoding a 190kDa protein, with a domain configuration similar to human C3. Multiple alignments of C3-like proteins revealed two processing sites, suggesting that Lox C3 is composed of three chains. Furthermore, the amino acids consensus sequences for the thioester was found, in addition to putative sequences responsible for FB binding. The phylogenetic analysis showed that Lox-C3 belongs to the same group as two C3 isoforms from the spider Hasarius adansoni (Family Salcitidae), showing 53% homology with these. This is the first characterization of a Loxosceles cDNA sequence encoding a human C3 homologue, and this finding, together with our previous finding of the expression of a FB-like molecule, suggests that this spider species also has a complement system. This work will help to improve our understanding of the innate immune system in these spiders and the ancestral structure of C3. PMID- 27259376 TI - Blurred world view: A study on the relationship between television viewing and the perception of the justice system. AB - Previous studies suggest that distorted representations of reality on television can lead to distorted perceptions of reality among viewers. In this study, 322 individuals in Austria reported their weekly television consumption and whether they believe that there is active practice of capital punishment in Austria, which has been abolished since 1968. The more television participants watched, the more likely they mistakenly believed that there is, or recently was, capital punishment in Austria, even when controlling for participants' age and education. It seems that television has the potential to influence viewers' perception and knowledge of core aspects of society. PMID- 27259378 TI - The newly appointed staff of the journal look for more reviewers. PMID- 27259386 TI - A nonlinear competitive model of the prostate tumor growth under intermittent androgen suppression. AB - Hormone suppression has been the primary modality of treatment for prostate cancer. However long-term androgen deprivation may induce androgen-independent (AI) recurrence. Intermittent androgen suppression (IAS) is a potential way to delay or avoid the AI relapse. Mathematical models of tumor growth and treatment are simple while they are capable of capturing the essence of complicated interactions. Game theory models have analyzed that tumor cells can enhance their fitness by adopting genetically determined survival strategies. In this paper, we consider the survival strategies as the competitive advantage of tumor cells and propose a new model to mimic the prostate tumor growth in IAS therapy. Then we investigate the competition effect in tumor development by numerical simulations. The results indicate that successfully IAS-controlled states can be achieved even though the net growth rate of AI cells is positive for any androgen level. There is crucial difference between the previous models and the new one in the phase diagram of successful and unsuccessful tumor control by IAS administration, which means that the suggestions from the models for medication can be different. Furthermore we introduce quadratic logistic terms to the competition model to simulate the tumor growth in the environment with a finite carrying capacity considering the nutrients or inhibitors. The simulations show that the tumor growth can reach an equilibrium state or an oscillatory state with the net growth rate of AI cells being androgen independent. Our results suggest that the competition and the restraint of a limited environment can enhance the possibility of relapse prevention. PMID- 27259380 TI - Positive Predictive Value of Mammographic Lymphography in the Evaluation of Patients with Breast Cancer: A Preliminary Study. AB - RATIONALE AND OBJECTIVES: The study aimed to investigate the positive predictive value (PPV) of mammographic lymphography (MLG) for assessing malignant breast disease and lymphatic metastasis in patients in a typical clinical setting. MATERIALS AND METHODS: Patients who underwent mammography with Breast Imaging Reporting and Data System (BI-RADS) category 4 or 5 lesions and had abnormal mammographic findings in the upper-outer quadrant of the breast were enrolled. Next, MLG was performed. A water-soluble agent was subcutaneously injected into the upper-outer periareolar region of the bilateral breast, and mammography was then performed. Morphologic characteristics, including lymphatic vessel development, the presence of lymphatic vessel defects, and dilation, were recorded for evaluation. RESULTS: Fifty-one patients with BI-RADS category 4 lesions and 40 patients with BI-RADS category 5 lesions were included in the study. Sixty-one patients were found to have malignant disease, whereas 30 patients were found to have benign disease. Morphologic characteristics were recorded for evaluation. The interobserver agreement was evaluated and was classified as excellent according to kappa analysis. The PPV of MLG characteristics for malignant breast disease and lymphatic metastasis was analyzed by logistic regression, and the presentation of a lymphatic vessel defect was the most predictive characteristic of a malignancy (PPV: 0.89; P value: 0.02) in patients with BI-RADS category 4 lesions. Meanwhile, in patients with malignant breast disease, the PPVs for predicting lymphatic metastasis with lymphatic vessel defect and dilation were 0.50 (P value: 0.02) and 0.67 (P value: <0.01), respectively. CONCLUSION: The assessment of morphologic characteristics by MLG has the potential to predict malignant breast disease and lymphatic metastasis. PMID- 27259379 TI - Imaging for the Pretreatment Staging of Small cell Lung Cancer: A Systematic Review. AB - BACKGROUND: Small cell lung cancer (SCLC) is an aggressive form of lung cancer. Accurate staging is essential to select the optimal treatment plan to maximize survival. No consensus exists on standard imaging modalities for pretreatment staging of SCLC. MATERIALS AND METHODS: We conducted a systematic review of the literature on imaging modalities in the pretreatment staging of SCLC. A systematic search of multiple databases identified relevant studies published from 2000 through June 2015. Outcomes of interest included test concordance, staging accuracy (sensitivity and specificity), choice of treatment, timeliness of treatment, and patient outcomes. RESULTS: The search identified 2880 citations; 7 studies met inclusion criteria, n = 408 patients. Six of the seven studies were deemed to have moderate risk of bias, and one was deemed to have high risk of bias. One of the studies reported test concordance, three studies reported comparative accuracy of testing strategies, and four studies reported the accuracy of a single imaging modality. Analysis from these studies revealed that fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) is more sensitive than multidetector CT for detecting osseous metastases, more sensitive than bone scintigraphy for detecting osseous metastases, and more sensitive for detecting any distant metastases. CONCLUSIONS: Evidence is sparse on the use of imaging in the pretreatment staging of SCLC. There is a lack of evidence on patient-oriented outcomes and a lack of evidence on whether comparative accuracy or effectiveness is associated with patient factors. We found low-strength evidence suggesting that FDG-PET/CT is more sensitive than CT and bone scintigraphy for detecting osseous metastases. PMID- 27259377 TI - Candida glabrata's recurrent infections: biofilm formation during Amphotericin B treatment. AB - Candida species are responsible for recurrent human infections, mostly in immunocompromised patients, due to their high vulnerability. Candida glabrata has a major role in systemic candidiasis and Amphotericin B (AmB), a polyene only used in hospitals, is frequently used to treat this disease. Lately, however, clinical evidences of Candida recurrent infections during these treatments are being described, probably due to biofilm (re)formation during this therapy. Thus, this work aims at inferring if C. glabrata biofilms are still being formed during AmB treatment. For that, C. glabrata biofilms were formed in the presence of AmB and analysed by dry weight. Matrix composition was analysed quantifying carbohydrates and, specifically, beta-1,3 glucans. Results demonstrated that, although in a lesser extent, C. glabrata is able to develop biofilms in the presence of AmB, with a thick extracellular matrix, with an increase on carbohydrates, especially beta-1,3 glucans. Therefore, it is confirmed that complex biofilms of C. glabrata can be formed during an AmB treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows new insights regarding recurrent candidiasis. The authors demonstrated that Amphotericin B did not totally prevent the development of biofilms during Candida glabrata's infection treatment and that the change in the biofilm matrices may have a high responsibility for the fail in the treatment of systemic candidiasis. PMID- 27259381 TI - Chitosan Promoted the Corneal Epithelial Wound Healing via Activation of ERK Pathway. AB - PURPOSE: To investigate the mechanism of chitosan promoting corneal wound healing though evaluating its effect on extracellular signal-regulated kinases (ERK) and p38 pathway activity in a rabbit animal model. METHODS: Cell proliferation and migration assay were performed 24 hours after chitosan treatment. The activity of ERK and p38 pathways was detected by using immunofluorescence and Western blotting in the presence of chitosan and an ERK inhibitor. In vivo study of epithelial debridement wounds was performed on 8 mm rabbit corneas in the presence of chitosan and an ERK pathway inhibitor. RESULTS: Immunostaining with Ki67 and migrating assay showed that chitosan could upregulate the cell proliferation and promote the cell migration. Chitosan activated the ERK pathway in 5 min to 30 min after treatment but did not affect the p38 pathway. ERK inhibitor PD98059 can inhibit the chitosan-stimulated ERK phosphorylation. Chitosan increased the corneal epithelial wound closure in organ culture and ERK inhibition with PD98059 blocked the effect of chitosan on wound healing. CONCLUSIONS: Chitosan promoted corneal epithelial proliferation and migration during the wound healing in rabbits' eye. Chitosan-stimulated epithelial wound healing is partially mediated through the activation of the ERK pathway but not the p38 pathway. PMID- 27259383 TI - A rare variant in CYP27A1 and its association with atopic dermatitis with high serum total IgE. AB - This study investigated rare variants associated with atopic dermatitis. We performed exome analyses on 37 patients who were diagnosed with atopic dermatitis by board-certified dermatologists and had total serum IgE levels greater than 1000 IU/ml. The exome analysis identified seven variants with <1% allele frequency in Asian (ASN) population of 1000 Genomes Project phase 1 data and >5% allele frequency in the atopic dermatitis exome samples. We then conducted a replication study using 469 atopic dermatitis patients with total serum IgE >=1000 IU/ml and 935 Japanese controls to assess the presence of these 7 candidate variants. The replication study confirmed that CYP27A1 rs199691576 (A/G) was associated with atopic dermatitis with high serum IgE levels (P = 0.012, odds ratio = 2.1). CYP27A1 is involved in the metabolism of vitamin D3, which plays important roles in modulating immune function. Previous studies have reported polymorphisms in vitamin D pathway genes that are associated with allergy-related phenotypes. Our data confirm the importance of genes regulating the vitamin D pathway in the development of atopic dermatitis. PMID- 27259387 TI - The intricate relationship between sexually antagonistic selection and the evolution of sex chromosome fusions. AB - Sex chromosomes are among the most evolutionarily labile features in some groups of animals. One of the mechanisms causing structural changes of sex chromosomes is fusion with an autosome. A recent study showed that the establishment rates of Y chromosome-autosome fusions are much higher than those of other fusions (i.e., X-autosome, W-autosome, and Z-autosome fusions) in fishes and reptiles. Although sexually antagonistic selection may be one of the most important driving forces of sex chromosome-autosome fusions, a previous theoretical analysis showed that sexually antagonistic selection alone cannot explain the excess of Y-autosome fusions in these taxa. This previous analysis, however, is based on the assumption that sexually antagonistic selection is symmetric, sexually antagonistic alleles are maintained only by selection-drift balance (i.e., no supply of mutation), and only one type of fusion arises within a population. Here, we removed these assumptions and made an individual-based model to simulate the establishment of sex chromosome-autosome fusions. Our simulations showed that the highest establishment rate of Y-autosome fusion can be achieved when the fusion captures a rare male-beneficial allele, if the recurrent mutation rates are high enough to maintain the polymorphism of alleles with asymmetric, sexually antagonistic effects. Our results demonstrate that sexually antagonistic selection can influence the dynamics of sex chromosome structural changes, but the type of fusion that becomes the most common depends on fusion rates, recurrent mutation rates, and selection regimes. Because the evolutionary fate of sex chromosome-autosome fusions is highly parameter-sensitive, further attempts to empirically measure these parameters in natural populations are essential for a better understanding of the roles of sexually antagonistic selection in sex chromosome evolution. PMID- 27259382 TI - Nuclear Transcription Factor Kappa B Downregulation Reduces Chemoresistance in Bone Marrow-derived Cells Through P-glycoprotein Modulation. AB - BACKGROUND AND AIMS: Nuclear transcription factor kappa B (NF-kappaB) is associated with many types of refractory cancer. However, despite multiple strategies to treat cancer and novel target drugs, multidrug resistance still causes relapses. The best-characterized mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein (P gp). Because the direct inhibition of this protein is very toxic, other methods of multidrug resistance (MDR) regulation have been proposed. The MDR-1 promoter sequence contains a kappaB site, which is recognized by NF-kappaB. The aim of this work was to characterize whether NF-kappaB modulation changes the response of bone marrow-derived cells (BMDCs) to chemotherapy. RESULTS: We exposed BMDCs to etoposide and doxorubicin, two of the most used antineoplastic drugs. BMDCs presented high tolerance to these drugs, which correlated with high intrinsic P gp activity and strong protein expression of NF-kappaB. To determine the mechanism behind the poor sensitivity of BMDCs to chemotherapy, we blocked the activity of the heterodimer protein NF-kappaB using the pharmacological inhibitor Bay 11-7085 and through the transfection of an adenovirus negative mutant of I kappa B alpha. The multidrug resistance phenotype of BMDCs was reversed by inhibiting the NF-kappaB pathway, and this change was accompanied by a decrease in P-gp activity. CONCLUSIONS: NF-kappaB is a possible target for improving the antineoplastic response. PMID- 27259384 TI - Impact of rosiglitazone safety alerts on oral antidiabetic sales trends: a countrywide study in Portugal. AB - Pharmacovigilance systems are important to monitor the safety of on-market drugs after approval. The aim of this study was to assess the impact of rosiglitazone safety alerts on trends in the sale of rosiglitazone and other oral antidiabetic drugs. An ecological study was conducted, using temporally aggregated data and linking safety alerts to countrywide sales of all oral antidiabetic drugs in Portugal from January 2002 to December 2012. Sales figures for oral antidiabetic drugs marketed in Portugal were supplied by IMS Health Portugal with a breakdown by active substance and fixed combinations. The number of defined daily doses per 1000 inhabitants per day (DIDs) of each oral antidiabetic drug sold to the estimated diabetic population using oral antidiabetic drugs in Portugal was calculated. Particular attention was paid to the case of rosiglitazone, with the results being adjusted for changes in rosiglitazone reimbursement policies. A total of four safety alerts were issued about rosiglitazone. Rosiglitazone sales registered an increase of 32.9% (0.202 DIDs; P < 0.001) after the first alert (risk of macular oedema or worsening of pre-existent macular oedema) in January 2006. After subsequent alerts about cardiovascular risks, this trend was not, however, repeated and sales fell. Following the January 2006 and January 2008 safety alerts, rosiglitazone sales described a long-term downward trend, with decreases of 3.75% (-0023 DIDs; P > 0.05) and 0.24% (-0.001 DIDs; P > 0.05), respectively. It is important to promote the dissemination and publication of drug safety alerts. PMID- 27259388 TI - Fermentative production of l-galactonate by using recombinant Saccharomyces cerevisiae containing the endogenous galacturonate reductase gene from Cryptococcus diffluens. AB - The GAR1 gene, encoding d-galacturonate reductase in Cryptococcus diffluens, was isolated, and the GAR1-expression plasmid was constructed by insertion of GAR1 downstream of the yeast constitutive promoter in the yeast-integrating vector. Recombinant Saccharomyces cerevisiae expressing C. diffluensd-galacturonate reductase from a genome integrated copy of the gene was cultured for use the conversion of d-galacturonic acid to l-galactonic acid. The optimum conditions for l-galactonic acid production were determined in terms of the initial concentration of d-galacturonic acid, fermentation pH, and mixed sugars. The following conditions yielded high efficiency in the conversion of d-galacturonic acid to l-galactonic acid in large-scale cultures: 0.1% initial d-galacturonic acid concentration, pH 3.5, and glucose as additional sugar. The aerobic condition was necessary for the conversion of d-galacturonic acid. Subculture of that recombinant was not showing to decrease of the d-galacturonic acid conversion rate even though it was repeated in ten generations. Culturing in scale-up, the conversion rate of d-galacturonic acid to l-galactonic acid was increased. PMID- 27259390 TI - Outcomes of Total Knee Arthroplasty in Patients With Poliomyelitis. AB - BACKGROUND: We report our experience with outcomes of poliomyelitis in the Asian population. METHODS: Sixteen total knee replacements in 14 patients with polio affected knees were followed up for at least 18 months. Follow-up assessment included scoring with the American Knee Society Score (AKSS), Oxford knee score, and Short Form 36 Health Survey scores. RESULTS: The mean AKSS improved from 25.59 preoperatively to 82.94 at 24 months, with greater improvement in the knee score. The mean Oxford knee score improved from 40.82 preoperatively to 20.53 at 24 months. The mean AKSS pain score rose from 2.35 to 47.66 at 24 months. The Short Form 36 Health Survey physical functioning and bodily pain scores improved for all patients. CONCLUSION: Primary total knee arthroplasty of poliomyelitis affected limbs shows good outcomes, improving quality of life, and decreasing pain. PMID- 27259385 TI - Reduction of epithelial secretion in male rat distal colonic mucosa by bile acid receptor TGR5 agonist, INT-777: role of submucosal neurons. AB - BACKGROUND: Recent evidence from rat neuron-free mucosa study suggests that the membrane bile acid receptor TGR5 decreases colonic secretion under basal and stimulated conditions. As submucosal neurons are key players in secretory processes and highly express TGR5, we investigated their role in TGR5 agonist induced inhibition of secretion and the pathways recruited. METHODS: TGR5 expression and localization were assessed in rat proximal (pC) and distal (dC) colon by qPCR and immunohistochemistry with double labeling for cholinergic neurons in whole-mount preparations. The influence of a selective (INT-777) or weak (ursodeoxycholic acid, UDCA) TGR5 agonist on colonic secretion was assessed in Ussing chambers, in dC preparation removing seromuscular +/- submucosal tissues, in the presence of different inhibitors of secretion pathways. KEY RESULTS: TGR5 mRNA is expressed in full thickness dC and pC and immunoreactivity is located in colonocytes and pChAT-positive neurons. Addition of INT-777, and less potently UDCA, decreased colonic secretion in seromuscular stripped dC by 58.17+/- 2.6%. INT-777 effect on basal secretion was reduced in neuron-free and TTX-treated mucosal-submucosal preparations. Atropine, hexamethonium, indomethacin, and L-NAME all reduced significantly INT-777's inhibitory effect while the 5-HT4 antagonist, RS-39604, and lidocaine abolished it. INT-777 inhibited stimulated colonic secretion induced by nicotine, but not cisapride, carbachol or PGE2. CONCLUSIONS & INFERENCES: TGR5 activation inhibits basal and stimulated distal colonic secretion in rats by acting directly on epithelial cells and also inhibiting submucosal neurons. This could represent a counter regulatory mechanism, at the submucosal level, of the known prosecretory effect of bile acids in the colon. PMID- 27259389 TI - Postoperative Pain Management After Primary Total Knee Arthroplasty: The Value of Liposomal Bupivacaine. AB - BACKGROUND: Multimodal pain protocols have been proposed to achieve improved long acting postoperative analgesia. Controlling postoperative pain after joint arthroplasty is especially important as it relates to patient satisfaction and outcomes. The purpose of this study was to compare the postoperative pain, time to ambulation, and overall narcotic usage between patients who received either a femoral nerve block with a periarticular bupivacaine injection or a periarticular bupivacaine and extended-release liposomal bupivacaine injection after primary total knee arthroplasty. METHODS: A total of 597 consecutive primary total knee arthroplasties performed between September 1, 2012 and August 31, 2014 received preoperative celecoxib, oxycodone, and transdermal scopolamine. Intraoperatively, patients either received a single-dose bupivacaine femoral nerve block along with 30-mL 0.25% bupivacaine periarticular injection (group A) or a 60-mL periarticular injection alone (20-mL liposomal bupivacaine, 30-mL 0.25% bupivacaine, and 10-mL saline; group B). The postoperative pain scores, narcotic usage, and time to ambulation were retrospectively collected from the electronic medical record. These outcomes were compared between treatment groups. RESULTS: There were 325 patients in group A compared with 272 in group B during the time frame. There was no difference among age, gender, race, and body mass index between the groups. Group B demonstrated a decreased need for breakthrough pain medication (16.9% vs 36.3% P < .001), decreased pain 12 hours postoperatively (3.2 vs 3.6 P < .003), and an earlier time to ambulation (29.5 hours vs 32.2 hours, P < .017). There was no difference in hospital length of stay (2.8 vs 2.6 days, P = .123). On controlling for demographic factors, patients in group B were able to ambulate 2.3 hours earlier than those in group A (coefficient = -2.3, P = .049). CONCLUSIONS: Liposomal bupivacaine resulted in a decrease need for breakthrough pain medication, improved pain scores at 12 hours, and an earlier time to ambulation compared to a combined femoral nerve block and periarticular bupivacaine injection. PMID- 27259391 TI - The Assessment of Blood Loss During Total Knee Arthroplasty When Comparing Intravenous vs Intracapsular Administration of Tranexamic Acid. AB - BACKGROUND: Administration of tranexamic acid topically and intravenously has demonstrated effectiveness in decreasing blood loss and transfusion rates. METHODS: We randomized 131 patients undergoing primary total knee arthroplasty to receive either intracapsular (69) or intravenous tranexamic acid (62). Postoperative blood loss was calculated using the formula derived by Nadler et al. The number of units transfused was recorded, as well as length of hospital stay. RESULTS: We found no statistically significant difference on calculated blood loss (postoperative day [POD] 1: 624 +/- 326 vs 644 +/- 292; P = .71, POD 2: 806 +/- 368 vs 835 +/- 319; P = .64, and POD 3: 1076 +/- 419 vs 978 +/- 343; P = .55). There was no difference in number of blood transfusions, length of stay, or complications. CONCLUSION: Intracapsular tranexamic acid is not inferior to intravenous tranexamic acid in decreasing blood loss and blood transfusion rate in primary total knee arthroplasty. PMID- 27259392 TI - Preoperative Pain and Function: Profiles of Patients Selected for Total Knee Arthroplasty. AB - BACKGROUND: Total knee arthroplasty (TKA) is an effective treatment to relieve pain and restore function in patients with advanced knee osteoarthritis. TKA utilization is growing rapidly, and the appropriateness of current TKA use is of great interest. We examined patient-reported preoperative pain and function profiles to understand symptom severity at the time of TKA decision. METHODS: Data were from the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. We included patients undergoing primary, unilateral TKAs between 2011 and 2014 for osteoarthritis and had data on the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain and Short-Form 36-item Physical Component Summary (PCS) score. We compared patient profiles across groupings by symptoms: (1) little pain and high function (KOOS >=70, PCS >=40); (2) little pain but poor function (KOOS >=70, PCS <40); (3) high pain but high function (KOOS <70, PCS >=40); and (4) high pain and poor function (KOOS <70, PCS <40). RESULTS: Of 6936 patients, 77% had high pain and poor function (group 4), 19% had high pain "or" poor function (groups 2-3), and 5% had little pain and high function before TKA (group 1). In group 1, 86% were constantly aware of their knee problem, 48% reported pain daily yet 5% experienced severe or extreme pain on stairs, and 1% pain in bed. Over half had a lot of limitations in vigorous activities. Compared with group 4, group 1 were older, less obese, more educated, and included more men and people reporting being healthy, less disabled, and happy (P < .05 for all). CONCLUSION: Most patients undergoing TKAs had significant pain and/or poor function. Our results provide critical information given the current debate of potentially inappropriate TKA utilization in the United States. PMID- 27259393 TI - Total Knee Arthroplasty in Obesity: In-Hospital Outcomes and National Trends. AB - BACKGROUND: Both the prevalence of obesity and the utilization rate of total knee arthroplasty are increasing. The rate and proportion of total knee arthroplasty (TKA) performed in the setting of obesity/morbid obesity is increasing significantly over time. METHODS: Using International Classification of Diseases Ninth Revision codes, we searched the National Hospitals Discharge Survey national database for patients admitted for primary TKA between 2001 and 2010. We then used International Classification of Diseases-Ninth Revision codes for obesity (body mass index = 30-40 kg/m2) and morbid obesity (body mass index, >= 40 kg/m2) to select the obese cohorts. RESULTS: We found 29,694 nonobese, 2645 obese, and 1150 morbidly obese patients. There was an increase in each group over time. The rate of obesity/morbid obesity was strongly correlated with time. Obese and morbidly obese patients were more likely to be younger, female, diabetic, and have Medicaid than nonobese patients. Obese and morbidly obese patients had shorter hospital stays and higher home discharge rates than nonobese patients. Obese and morbidly obese patients had lower transfusion rates, shorter hospital stays, and no increase in inpatient wound infection or venous thromboembolic complications than nonobese patients. The Midwest region saw a greater burden of obese TKA patients. CONCLUSION: With the right measures and precautions, satisfactory inhospital outcomes are possible in the obese patient after primary TKA. A limitation of this study is short inhospital stay of the index procedure as complications may present later after discharge. PMID- 27259394 TI - [Miescher's cheilitis]. PMID- 27259395 TI - [Gingival enlargement: Practical management]. PMID- 27259396 TI - Insight into the mechanisms of enhanced retinal transduction by the engineered AAV2 capsid variant -7m8. AB - Recently, we described a modified AAV2 vector-AAV2-7m8-having a capsid-displayed peptide insertion of 10 amino acids with enhanced retinal transduction properties. The insertion of the peptide referred to as 7m8 is responsible for high-level gene delivery into deep layers of the retina when virus is delivered into the eye's vitreous. Here, we further characterize AAV2-7m8 mediated gene delivery to neural tissue and investigate the mechanisms by which the inserted peptide provides better transduction away from the injection site. First, in order to understand if the peptide exerts its effect on its own or in conjunction with the neighboring amino acids, we inserted the 7m8 peptide at equivalent positions on three other AAV capsids, AAV5, AAV8, and AAV9, and evaluated its effect on their infectivity. Intravitreal delivery of these peptide insertion vectors revealed that only AAV9 benefited from 7m8 insertion in the context of the retina. We then investigated AAV2-7m8 and AAV9-7m8 properties in the brain, to better evaluate the spread and efficacy of viral transduction in view of the peptide insertion. While 7m8 insertion led to higher intensity gene expression, the spread of gene expression remained unchanged compared to the parental serotypes. Our results indicate that the 7m8 peptide insertion acts by increasing efficacy of cellular entry, with little effect on the spread of viral particles in neural tissue. The effects of peptide insertion are capsid and tissue dependent, highlighting the importance of the microenvironment in gene delivery using AAV. Biotechnol. Bioeng. 2016;113: 2712-2724. (c) 2016 Wiley Periodicals, Inc. PMID- 27259397 TI - Improving Medical Students' Application of Knowledge and Clinical Decision-Making Through a Porcine-Based Integrated Cardiac Basic Science Program. AB - OBJECTIVE: Despite the concerted effort of modern undergraduate curriculum designers, the ability to integrate basic sciences in clinical rotations is an ongoing problem in medical education. Students and newly qualified doctors themselves report worry about the effect this has on their clinical performance. There are examples in the literature to support development of attempts at integrating such aspects, but this "vertical integration" has proven to be difficult. We designed an expert-led integrated program using dissection of porcine hearts to improve the use of cardiac basic sciences in clinical medical students' decision-making processes. To our knowledge, this is the first time in the United Kingdom that an animal model has been used to teach undergraduate clinical anatomy to medical students to direct wider application of knowledge. METHODS: Action research methodology was used to evaluate the local curriculum and assess learners needs, and the agreed teaching outcomes, methods, and delivery outline were established. A total of 18 students in the clinical years of their degree program attended, completing precourse and postcourse multichoice questions examinations and questionnaires to assess learners' development. RESULTS: Student's knowledge scores improved by 17.5% (p = 0.01; students t test). Students also felt more confident at applying underlying knowledge to decision-making and diagnosis in clinical medicine. An expert teacher (consultant surgeon) was seen as beneficial to students' understanding and appreciation. CONCLUSIONS: This study outlines how the development of a teaching intervention using porcine-based methods successfully improved both student's knowledge and application of cardiac basic sciences. We recommend that clinicians fully engage with integrating previously learnt underlying sciences to aid students in developing decision-making and diagnostic skills as well as a deeper approach to learning. PMID- 27259399 TI - Synthesis and evaluation of biphenyl derivatives as potential downregulators of VEGF protein secretion and telomerase-related gene expressions. AB - A group of 47 biphenyl functionalized compounds, prepared by means of Suzuki couplings, has been investigated for their cytotoxicity on two tumoral cell lines (HT-29 and MCF-7) and one non tumoral cell line (HEK-293). 29 selected compounds have been investigated for their ability to inhibit the production of the vascular endothelial growth factor (VEGF). Subsequently, the capacity of the compounds to downregulate the expression of the VEGF, h-TERT and c-Myc genes, the two latter involved in the control of the activation of telomerase, has also been determined. PMID- 27259400 TI - The influence of halogen substituents on the biological properties of sulfur containing flavonoids. AB - A series of halogen-substituted tricyclic flavonoids containing a 1,3-dithiol-2 ylium moiety has been synthesized from the corresponding 3-dithiocarbamic flavanones. The influence of halogen substituents on the antibacterial properties of the tricyclic flavonoids has been investigated against Staphylococcus aureus and Escherichia coli. On going from fluorine to iodine, these compounds exhibit good to excellent inhibitory properties against both Gram-positive and Gram negative pathogens. These results suggest that size is the main factor for the change in potency rather than polarity/electronics. PMID- 27259401 TI - Axial PEGylation of Tin Octabutoxy Naphthalocyanine Extends Blood Circulation for Photoacoustic Vascular Imaging. AB - Attachment of polyethylene glycol (PEG) can prolong blood circulation of biological molecules, a useful trait for a vascular imaging agent. Here, we present a route for modifying octabutoxy naphthalocyanine (ONc) with PEG, via axial conjugation following ONc chelation with Sn(IV) chloride (Sn-ONc). Tin chelation caused ONc absorbance to shift from 860 to 930 nm. Hydroxy terminated PEG was treated with sodium and then was axially attached to the tin, generating PEG-Sn-ONc. Unlike ONc or Sn-ONc, PEG-Sn-ONc was soluble in methanol. ONc and PEG Sn-ONc were dissolved in polysorbate solutions and administered to mice intravenously. PEG-Sn-ONc demonstrated substantially longer blood circulation time than ONc, with a 4 times longer half-life and a nearly 10 times greater area under the curve. PEG-Sn-ONc gave rise to photoacoustic contrast and could be used for noninvasive brain vessel imaging even 24 h following injection. This work demonstrates that nonmetallic naphthalocyanines can be chelated with tin, and be axially modified with PEG for enhanced circulation times for long-term vascular imaging with photoacoustic tomography. PMID- 27259398 TI - Delivery strategies and potential targets for siRNA in major cancer types. AB - Small interfering RNA (siRNA) has gained attention as a potential therapeutic reagent due to its ability to inhibit specific genes in many genetic diseases. For many years, studies of siRNA have progressively advanced toward novel treatment strategies against cancer. Cancer is caused by various mutations in hundreds of genes including both proto-oncogenes and tumor suppressor genes. In order to develop siRNAs as therapeutic agents for cancer treatment, delivery strategies for siRNA must be carefully designed and potential gene targets carefully selected for optimal anti-cancer effects. In this review, various modifications and delivery strategies for siRNA delivery are discussed. In addition, we present current thinking on target gene selection in major tumor types. PMID- 27259402 TI - A Single Dose of Prednisolone as a Modulator of Undercarboxylated Osteocalcin and Insulin Sensitivity Post-Exercise in Healthy Young Men: A Study Protocol. AB - BACKGROUND: Undercarboxylated osteocalcin (ucOC) increases insulin sensitivity in mice. In humans, data are supportive, but the studies are mostly cross-sectional. Exercise increases whole-body insulin sensitivity, in part via ucOC, while acute glucocorticoid treatment suppresses ucOC in humans and mice. OBJECTIVES: A single dose of prednisolone reduces the rise in ucOC produced by exercise, which partly accounts for the failed increase in insulin sensitivity following exercise. METHODS: Healthy young men (n=12) aged 18 to 40 years will be recruited. Initial assessments will include analysis of fasting blood, body composition, aerobic power (VO2peak), and peak heart rate. Participants will then be randomly allocated, double-blind, to a single dose of 20 mg of prednisolone or placebo. The two experimental trials will involve 30 minutes of interval exercise (90%-95% peak heart rate), followed by 3 hours of recovery and 2 hours of euglycaemic- hyperinsulinaemic clamp (insulin clamp). Seven muscle biopsies and blood samples will be obtained at rest, following exercise and post-insulin clamps. RESULTS: The study is funded by the National Heart Foundation of Australia and Victoria University. Enrollment has already commenced and data collection will be completed in 2016. CONCLUSION: If the hypothesis is confirmed, the study will provide novel insights into the potential role of ucOC in insulin sensitivity in human subjects and will elucidate pathways involved in exercise-induced insulin sensitivity. PMID- 27259460 TI - A systematic review of studies examining the rate of lung function decline in patients with cystic fibrosis. AB - A systematic review was performed (i) to describe the reported overall rate of progression of CF lung disease quantified as FEV1%predicted decline with age, (ii) to summarise identified influencing risk factors and (iii) to review methods used to analyse CF lung disease progression data. A search of publications providing FEV1%predicted values over age was conducted in PUBMED and EMBASE. Baseline and rate of FEV1%predicted decline were summarised overall and by identified risk factors. Thirty-nine studies were included and reported variable linear rates of lung function decline in patients with CF. The overall weighted mean FEV1%predicted over age was graphically summarised and showed a nonlinear, time-variant decline of lung function. Compared to their peers, Pseudomonas aeruginosa infection and pancreatic insufficiency were most commonly associated with lower baseline and more rapid FEV1%predicted declines respectively. Considering nonlinear models and drop-out in lung disease progression, analysis is lacking and more studies are warranted. PMID- 27259461 TI - TERRA Incognita at chromosome ends. PMID- 27259462 TI - Mitochondria mediate septin cage assembly to promote autophagy of Shigella. AB - Septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic Shigella flexneri and promote their targeting to autophagosomes. However, the processes underlying septin cage assembly, and whether they influence S. flexneri proliferation, remain to be established. Using single-cell analysis, we show that the septin cages inhibit S. flexneri proliferation. To study mechanisms of septin cage assembly, we used proteomics and found mitochondrial proteins associate with septins in S. flexneri infected cells. Strikingly, mitochondria associated with S. flexneri promote septin assembly into cages that entrap bacteria for autophagy. We demonstrate that the cytosolic GTPase dynamin-related protein 1 (Drp1) interacts with septins to enhance mitochondrial fission. To avoid autophagy, actin-polymerising Shigella fragment mitochondria to escape from septin caging. Our results demonstrate a role for mitochondria in anti-Shigella autophagy and uncover a fundamental link between septin assembly and mitochondria. PMID- 27259464 TI - Efficacy of parent-delivered behavioral therapy for primary complex motor stereotypies. AB - AIM: Primary complex motor stereotypies (CMS) are persistent, patterned, repetitive, rhythmic movements in young people with typical development. This study evaluated the efficacy of an instructional DVD as a home-based, parent administered, behavioral therapy for primary CMS. METHOD: Eighty-one children with primary CMS were enrolled. Primary outcome measures included the Stereotypy Severity Scale (SSS) - Motor and Impairment scores, and Stereotypy Linear Analog Scale (SLAS). Mean CMS onset was 13.4 months (SD 13.1). Eligibility required observed CMS. Psychiatric disorders were not exclusionary and a stable medication regimen was required. Intellectual disability, neurological disorder, autism spectrum disorder, and tics were exclusionary. Initial assessments were completed via REDCap before receipt of the DVD. Fifty-four of the 81 children (34 male, 20 female; mean age 8y 2mo, SD 1.42, range 7-14y) completed assessments at 1, 2, or 3 months after receiving the DVD. RESULTS: Reductions (baseline to last assessment) in SSS Motor, SSS Impairment, and SLAS scores (all p<0.001) represented change ratios of -15%, -24%, and a -20% respectively. Greatest relative treatment benefit was observed by younger children (ages 7-8y), and by 1 month after receipt of DVD, while a parent global assessment scale showed progressive improvement throughout the study. INTERPRETATION: An instructional DVD for parent-delivered behavioral therapy was a safe, effective intervention for primary CMS. PMID- 27259463 TI - Haemodiafiltration at increased plasma ionic strength for improved protein-bound toxin removal. AB - AIM: Protein-bound uraemic toxin accumulation causes uraemia-associated cardiovascular morbidity. Enhancing the plasma ionic strength releases toxins from protein binding and makes them available for removal during dialysis. This concept was implemented through high sodium concentrations ([Na+ ]) in the substituate of pre-dilution haemodiafiltration at increased plasma ionic strength (HDF-IPIS). METHODS: Ex vivo HDF-IPIS with blood tested increasing [Na+ ] to demonstrate efficacy and haemocompatibility. Haemocompatibility was further assessed in sheep using two different HDF-IPIS set-ups and [Na+ ] between 350 and 600 mmol L-1 . Safety and efficacy of para-cresyl sulphate (pCS) and indoxyl sulphate (IS) removal was further investigated in a randomized clinical pilot trial comparing HDF-IPIS to HD and HDF. RESULTS: Compared to [Na+ ] of 150 mmol L 1 , ex vivo HDF-IPIS at 500 mmol L-1 demonstrated up to 50% higher IS removal. Haemolysis in sheep was low even at [Na+ ] of 600 mmol L-1 (free Hb 0.016 +/- 0.001 g dL-1 ). In patients, compared to HD, a [Na+ ] of 240 mmol L-1 in HDF-IPIS resulted in 40% greater reduction (48.7 +/- 23.6 vs. 67.8 +/- 7.9%; P = 0.013) in free IS. Compared to HD and HDF (23.0 +/- 14.8 and 25.4 +/- 10.5 mL min-1 ), the dialytic clearance of free IS was 31.6 +/- 12.8 mL min-1 (P = 0.017) in HDF-IPIS, but [Na+ ] in arterial blood increased from 132 +/- 2 to 136 +/- 3 mmol L-1 (0 vs. 240 min; P < 0.001). CONCLUSION: HDF-IPIS is technically and clinically feasible. More effective HDF-IPIS requires higher temporary plasma [Na+ ], but dialysate [Na+ ] has to be appropriately adapted to avoid sodium accumulation. PMID- 27259465 TI - The unexpected beneficial role of smoking in preeclampsia. AB - We have recently investigated the association between the risk of developing PE and clinical, hemostatic, inflammatory and genetic parameters of 108 severe preeclamptic women. A multivariate logistic regression analysis was performed to assess what variables are independent risk factors for PE. Univariate analysis was performed including the variables in age, smoking condition, multiple pregnancy, blood group, phenotypes and alleles of IL-4, IL-5, IL-10, IL-6, IL-8, IL-12, IL-1beta, IFN-gamma, TNF-alpha, and the plasma levels of FVII, FVIIa, FVIIa-AT, FVIII, FVW, ADAMTS13, D-Di, PAI-1, ADMA. Those variables whose P<0.20 (smoking, multiple pregnancy, blood group, phenotype IL-6, IFN-gamma allele, IL 10 allele and FVII) were selected to the multivariate logistic regression. In the final model, only FVII, IFN-gamma allele and smoking were independently associated to severe PE (P<0.0001, P<0.0001 and P=0.008, respectively). Increased FVII plasma levels and IFN-gamma "T" allele were associated to an increased probability of developing PE (OR 1.001, 95% CI [1.001-1.002], and OR 4.81 95% CI [2.42-9.60], respectively). On the other hand, smoker status was associated with a 4.72 decreased chance of PE occurrence (OR 4.72, 95% CI [1.51-14.75]). In this article we also reviewed the studies that investigate the risk of PE in pregnant women who smoked, as well as the effect of tobacco extract in cells or animal models. The hypotheses proposed to explain the biological mechanism by which smoking during pregnancy reduces the risk of PE was also discussed. PMID- 27259466 TI - The clinical utility of mass spectrometry based protein assays. AB - Reports of mass spectrometry based assays for peptides and proteins have become increasingly common in the literature. The growing interest of mass spectrometry for use in clinical laboratories has been primarily driven by the inherent selectivity of the platform relative to more traditional platforms such as immunoassays. However, the adoption of mass spectrometry for peptide and protein analysis in the clinic has been relatively slow compared its adoption in non clinical laboratories such as in biomarker discovery efforts or within laboratories that support pharmaceutical and academic research. Here, we review some of the successful reports of MS based assays for human proteins in multiple stages of assay research, and describe how and why the platform was employed in order to demonstrate where and when mass spectrometry based assays will have value in the future. PMID- 27259467 TI - Alpha-1 antitrypsin: Associated diseases and therapeutic uses. PMID- 27259468 TI - NETosis markers: Quest for specific, objective, and quantitative markers. AB - More than 10years have passed since the discovery of neutrophil extracellular traps (NETs) in 2004. NETs are extracellular web-like DNA decorated with antimicrobial proteins, which are released from activated neutrophils. The state of neutrophils with NET formation is called NETosis. It has been realized that NETosis includes suicidal NETosis and vital NETosis. The former state means cell death of neutrophils, whereas the latter state preserves living neutrophilic functions. Although both suicidal and vital NETosis play essential roles in elimination of microorganisms, excessive formation of NETs, especially the ones derived from suicidal NETosis, can harm the hosts. Therefore, the discovery of NETosis markers and development of evaluation methods are important. In this review, we compare the methods for evaluating NETosis, including immunocytological and immunohistological detection of co-localized neutrophil derived proteins and extracellular DNA, and citrullinated histones, detection of NET remnants in fluid samples, and flow cytometric detection of cell-appendant NET components, with focus on the specificity, objectivity, and quantitativity. Since the gold standard marker of NETosis or method of NET detection has not been established yet, researchers should choose the most appropriate marker or method in each situation based on the knowledge of the respective virtues and faults. PMID- 27259469 TI - The need for ethics as well as evidence in evidence-based medicine. PMID- 27259470 TI - Most systematic reviews of adverse effects did not include unpublished data. AB - OBJECTIVES: We sought to identify the proportion of systematic reviews of adverse effects which search for unpublished data and the success rates of identifying unpublished data for inclusion in a systematic review. STUDY DESIGN AND SETTING: Two reviewers independently screened all records published in 2014 in the Database of Abstracts of Reviews of Effects (DARE) for systematic reviews where the primary aim was to evaluate an adverse effect or effects. Data were extracted on the types of adverse effects and interventions evaluated, sources searched, how many unpublished studies were included, and source or type of unpublished data included. RESULTS: From 9,129 DARE abstracts, 348 met our inclusion criteria. Most of these reviews evaluated a drug intervention (237/348, 68%) with specified adverse effects (250/348, 72%). Over a third (136/348, 39%) of all the reviews searched, a specific source for unpublished data, such as conference abstracts or trial registries, and nearly half of these reviews (65/136, 48%) included unpublished data. An additional 13 reviews included unpublished data despite not searching specific sources for unpublished studies. Overall, 22% (78/348) of reviews included unpublished data/studies. CONCLUSION: Most reviews of adverse effects do not search specifically for unpublished data but, of those that do, nearly half are successful. PMID- 27259471 TI - Roles of O-GlcNAc in chronic diseases of aging. AB - O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention. PMID- 27259472 TI - Effects of working memory training on children born preterm. AB - Researchers have reported benefits of working memory training in various populations, however, the training gains in preterm population is still inadequately studied. This study aimed to investigate the transfer and lasting effects of an online working memory training program on a group of preterm children aged between 4 and 6 years (mean gestational age = 28.3 weeks; mean birth weight = 1153 grams). Children were asked to perform the Cogmed JM at home for approximately 15 minutes a day, 5 days a week for 5 weeks. Their nontrained working memory and attention were assessed pre-training, post-training, and at 5 week follow-up. Parent ratings on children's executive functions were obtained at the three time points. Results revealed that significant improvements in verbal working memory was emerging in preterm children at 5-week follow-up, while significant gains in visuospatial working memory was found post-training and at 5 week follow-up in age-matched term-born children. These results indicated that working memory training has benefits on preterm children; however, the gains are different from those observed in term-born children. No significant differences in attention and parent-rated EF were found in either group across time. The possible explanations for the training benefits observed in preterm children were discussed. PMID- 27259473 TI - Outdoor and indoor monitoring of livestock-associated Culicoides spp. to assess vector-free periods and disease risks. AB - BACKGROUND: Within the last few decades Culicoides spp. (Diptera: Ceratopogonidae) emerged Europe-wide as a major vector for epizootic viral diseases e.g. caused by Bluetongue (BT) or Schmallenberg virus. In accordance with the EU regulation 1266/2007, veterinary authorities are requested to determine vector-free periods for loosing trade and movement restrictions of susceptible livestock. Additionally, the widely used basic reproduction number [Formula: see text] is optionally applied for risk assessment of vector-borne diseases. Values of R0 < 1 indicate periods with no disease transmission risk. For the determination of vector-free period and R0 a continuously operating daily Culicoides spp. monitoring in Vienna (Austria) was established. It covered the period 2009-2013 and depicts the seasonal vector abundance indoor and outdoor. Future BT and African horse sickness (AHS) outbreak risks were estimated by projecting R0 to climate change scenarios. Therefore, temperature-dependent vector parameters were applied. RESULTS: The vector-free period lasted about 100 days inside stables, while less than five Culicoides were trapped outdoors on 150 days per season, i.e. winter half year. Additionally, the potential outbreak risk was assessed for BT and AHS. For BT, a basic reproduction number of R0 > 1 was found each year between June and August. The periods without transmission risk, i.e. R0 < 1, were notably higher (200 days). Contrary, values of R0 < 1 were estimated for AHS during the whole period. Finally, the basic reproduction numbers were projected to the future by using temperature forecasts for the period 2014-2100. While the mean summer peak values for BT increase from of R0 = 2.3 to R0 = 3.4 until 2100 (1.1/100 years), no risk for AHS was estimated even under climate warming assumptions. CONCLUSIONS: Restrictions to trade and movement are always associated with an economic impact during epidemic diseases. To minimize these impacts, risk assessments based on the vector-free period or the basic reproduction number R0 can essentially support veterinary authorities to improve protection and control measurements. PMID- 27259474 TI - Granular cell tumor presenting in the scrotum of a pediatric patient: a case report and review of the literature. AB - BACKGROUND: Granular cell tumors are neoplasms of Schwann cell origin. They typically arise in the head and neck of adults, with the tongue being the most common location; granular cell tumors of male genitalia are exceedingly rare. We identified only eight prior cases of scrotal granular cell tumor in the literature, and only one was in a child. Herein, we report a second case of childhood scrotal granular cell tumor and provide a review of the most relevant literature. CASE PRESENTATION: A fifteen-year-old hispanic boy was referred to our hospital's pediatric surgery service for a painless and firm scrotal mass. Clinical impression was that of an epidermal inclusion cyst. There was no evidence of associated medical problems from the clinical history and physical examination. Surgical enucleation of the lesion demonstrated a solid nodule with morphological and immunohistochemical features consistent with a benign granular cell tumor. CONCLUSIONS: This is the second case reported of a scrotal granular cell tumor in a child. Although genital granular cell tumors are rare, and most are benign, careful clinical examination, complete surgical excision, expert histologic evaluation, and a close follow-up are recommended for accurate diagnosis and to rule out eventual malignancy. PMID- 27259476 TI - Incorporating health literacy in education for socially disadvantaged adults: an Australian feasibility study. AB - BACKGROUND: Adult education institutions have been identified as potential settings to improve health literacy and address the health inequalities that stem from limited health literacy. However, few health literacy interventions have been tested in this setting. METHODS: Feasibility study for an RCT of the UK Skilled for Health Program adapted for implementation in Australian adult education settings. Implementation at two sites with mixed methods evaluation to examine feasibility, test for change in participants' health literacy and pilot test health literacy measures. RESULTS: Twenty-two socially disadvantaged adults with low literacy participated in the program and received 80-90 hours of health literacy instruction. The program received institutional support from Australia's largest provider of vocational education and training and was feasible to implement (100 % participation; >90 % completion; high teacher satisfaction). Quantitative results showed improvements in participants' health literacy skills and confidence, with no change on a generic measure of health literacy. Qualitative analysis identified positive student and teacher engagement with course content and self-reported improvements in health knowledge, attitudes, and communication with healthcare professionals. CONCLUSIONS: Positive feasibility results support a larger RCT of the health literacy program. However, there is a need to identify better, multi-dimensional measures of health literacy in order to be able to quantify change in a larger trial. This feasibility study represents the first step in providing the high quality evidence needed to understand the way in which health literacy can be improved and health inequalities reduced through Australian adult education programs. PMID- 27259475 TI - MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses. AB - Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE's utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an immune-modulatory probiotic. Using these datasets, we demonstrate new capabilities, including accurate forecasting of microbial dynamics, prediction of stable sub-communities that inhibit pathogen growth, and identification of bacteria most crucial to community integrity in response to perturbations. PMID- 27259477 TI - Inhibition of Notch 1 receptor influenced the differentiation of Lin-CD45RA dendritic cell precursors within ovarian carcinoma microenvironment. AB - BACKGROUND: Previous evidence suggested that the differentiation of Lin-CD45RA-DC precursors were prior to plasmcytoid dendritic cells (pDCs) than myeloid dendritic cells (mDCs) within ovarian cancer microenvironment. However, the mechanism is still unclear. Therefore, we investigated the function of Notch 1 signal pathway in the differentiation of Lin-CD45RA-DC precursors. METHODS: The CD34+ hematopoietic stem cells were extracted from umbilical cord blood in term parturition, and Lin-CD45RA-DC precusors were separated and induced mature. Expression of Notch1 receptor and ligands in Lin-CD45RA-DC precusors was detected by Real-time PCR and was down-regulated by shRNA or gamma-secretase inhibitor (GSI). Flow cytometry was used to analyze the subset of DCs with or without SKOV3 culture supernatants. IL-12 level was detected by ELISA. RESULTS: Expression of Notch1 receptors and ligands were detected in Lin-CD45RA-DC precursor cells. The Notch1 mRNA in Lin-CD45RA-DC precursors can be down-regulated by shRNA-Notch1 lentivirus transfection and GSI. ShRNA mediated Notch 1 knock-down significantly differentiated less plasmcytoid dendritic cells (pDCs), but generated more myeloid dendritic cells (mDCs), and this would not be influenced by the supernatant of the ovarian carcinoma cell line. GSI had the same effect in the differentiation of pDC. The secretion of IL-12 significantly increased after Notch1 knock-down with or without SKOV3 culture supernatants. CONCLUSIONS: Notch1 is an important signaling pathway in the differentiation of Lin-CD45RA-DC precursor cells to plasmcytoid dendritic cells (pDCs). And this would not be affected by the supernatant of the ovarian carcinoma cell line. PMID- 27259478 TI - The novel in vitro reanimation of isolated human and large mammalian heart-lung blocs. AB - BACKGROUND: In vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study. RESULTS: Systolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2 +/- 11/7 and 74/3 +/- 17/5 mmHg, respectively, with associated native heart rates of 80 +/ 7 and 96 +/- 16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation. CONCLUSIONS: We report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens. PMID- 27259479 TI - Estimating epidemiological data of Multiple sclerosis using hospitalized data in Shandong Province, China. AB - BACKGROUND: Multiple sclerosis (MS) is a rare chronically debilitating disease. There are few reports on the burden of disease of MS and prevalence in China. The authors intended to estimate disease burden and prevalence of MS in Shandong Province using available epidemiologic data. METHODS: Prevalence was calculated using DISMOD II software based on incidence extrapolated from hospitalization data, case fatality and remission rate from literature as input indexes. Disability-adjusted life year (DALY) was computed with epidemiologic indexes estimated by DISMOD II program. RESULTS: The prevalence of MS was estimated to be 3.7(95 % CI: 1.65-5.8) and 6.7(95 % CI: 2.7-9.56) cases per 100,000 people for males and for females, respectively. The mean age at onset of MS was 36.0(43.0 +/ 30.0 years in males and 33.7(43.4 +/- 29.7) years in females. Duration of the disease was estimated to be 34.0 (31.6 +/- 21.0) years for males and 39.5(34.9 +/ 21.8) years for females. The disease burden in disability-adjusted life years was 3316, comprised of 903 (27.2 %) years of life lost (YLL) and 2413 (72.8 %) years lived with disability (YLD). CONCLUSIONS: Our study highlighted that population in Shandong Province had a high prevalence of MS and the patients had a heavy disease burden. It also revealed that the results obtained in this paper would be useful to provide a reference for establishing specific healthcare policies for this rare disease in Shandong Province. PMID- 27259481 TI - Overcorrecting minus lens therapy in patients with intermittent exotropia: Should it be the first therapeutic choice? AB - To evaluate medium-term outcomes of overminus lens treatment in patients with intermittent exotropia [X(T)]. A retrospective analysis was performed of the outcomes of 19 children with X(T) who were prescribed overminus lens (-2.00 to 4.00 D) for a median period of 18 months (6-33). The success was evaluated using two assessment methods: 1. Newcastle Control System (NCS), and 2. Jampolsky's assessment. The mean age of the patients was 6.8 +/- 3.3 years (range 3-14 years). After the therapy, the median NCS score significantly improved from 5 to 1 (p < 0.001). Sixteen children (84 %) showed a NCS score of 2 or less after overminus lens treatment. According to Jampolsky's assessment, 84 % of the patients showed marked improvement from the baseline (47 % had qualitative improvement, 37 % quantitative decrease in the angle of deviation in addition to a qualitative improvement). The median pre-treatment distant angle decreased from 25 prism diopters (PD) to 18 PD after the treatment (p = 0.002). Overcorrecting minus lens treatment has a reasonable rate of success in the medium term and may be advised as primary therapeutic alternative for X(T). Both NCS and Jampolsky's scoring system appear to be useful and comparable for follow-up of patients with X(T). PMID- 27259480 TI - The status of maternal and newborn health care services in Zanzibar. AB - BACKGROUND: It is estimated that 287,000 women worldwide die annually from pregnancy and childbirth-related conditions, and 6.9 million under-five children die each year, of which about 3 million are newborns. Most of these deaths occur in sub-Saharan Africa. The maternal health situation in Tanzania mainland and Zanzibar is similar to other sub-Saharan countries. This study assessed the availability, accessibility and quality of emergency obstetric care services and essential resources available for maternal and child health services in Zanzibar. METHODS: From October and November 2012, a cross-sectional health facility survey was conducted in 79 health facilities in Zanzibar. The health facility tools developed by the Averting Maternal Death and Disability program were adapted for local use. RESULTS: Only 7.6 % of the health facilities qualified as functioning basic EmONC (Emergency Obstetric and Neonatal Care) facilities and 9 % were comprehensive EmONC facilities. Twenty-eight percent were partially performing basic EmONC and the remaining 55.7 % were not providing EmONC. Neonatal resuscitation was performed in 80 % of the hospitals and only 17.4 % of the other health facilities that were surveyed. Based on World Health Organisation (WHO) criteria, the study revealed a gap of 20 % for minimum provision of EmONC facilities per 500,000 population. The met need at national level (proportion of women with major direct obstetric complications treated in a health facility providing EmONC) was only 33.1 % in the 12 months preceding the survey. The study found that there was limited availability of human resources in all visited health facilities, particularly for the higher cadres, as per Zanzibar minimum staff requirements. CONCLUSION: There is a need to strengthen human resource capacity at primary health facilities through training of health care providers to improve EmONC services, as well as provision of necessary equipment and supplies to reduce workload at the higher referral health facilities and increase geographic access. PMID- 27259482 TI - [Arthroscopic subacromial decompression]. AB - OBJECTIVE: Coracoacromial ligament release to widen the subacromial space, resection of the anterior undersurface of the acromion and, if needed, caudal exophytes at the acromioclavicular joint. INDICATIONS: All types of outlet impingement after 3 months of conservative treatment. CONTRAINDICATIONS: Impingement syndrome with instability/muscular imbalance, massive rotator cuff tear, unstable os acromionale, posterior-superior impingement, joint infection, freezing phase of a secondary frozen shoulder. SURGICAL TECHNIQUE: Lateral decubitus position with traction device for the arm. Diagnostic arthroscopy of the glenohumeral joint via standard portals. With arthroscope moved to the subacromial space, bursectomy, electrosurgical release of coracoacromial ligament, resection of acromial hook through standard posterior portal. POSTOPERATIVE MANAGEMENT: Physiotherapy or self-exercises on postoperative day 1, pain-adapted analgesia to avoid shoulder stiffness. RESULTS: Several studies present positive long-term results compared to conservative treatment (and open acromioplasty) for partial rotator cuff tears and for elderly patients. With a 20 year follow-up, successful results have been achieved for all patients with isolated impingement syndrome. PMID- 27259483 TI - [Amputation and exarticulation of the lesser toes]. AB - OBJECTIVE: Amputations and exarticulations of the toes may be necessary due to several reasons. The goal is to remove necrosis or infection prior to its spread to the midfoot region. From a functional or cosmetic point of view, amputation/exarticulation of a single toe plays no major role. However, this can be different with exarticulation of several toes. INDICATIONS: Necrosis, trauma, infection, tumor, deformity. CONTRAINDICATIONS: Conditions where amputation/exarticulation of a toe is insufficient, e. g., in progressing peripheral arterial disease. SURGICAL TECHNIQUE: The toe can either be amputated through the distal phalanx or exarticulated in the metatarsophalangeal joint. POSTOPERATIVE MANAGEMENT: Orthopedic shoes or orthotic devices are rarely necessary when a single toe is amputated/exarticulated. However, concomitant deformities of the foot have to be thoroughly addressed. If more than one toe is amputated, silicone spacers may be necessary to prevent the remaining toes from deviating. RESULTS: Amputations and exarticulations of the toes are frequent and the procedure is technically simple. However, the complication rate is high due to typical indications making amputation necessary. PMID- 27259484 TI - Safety and efficacy of high-rate cutoff and long detection interval ICD programming in secondary prevention patients. AB - Several trials demonstrated that a long detection interval and a high-rate cutoff reduced implantable cardioverter-defibrillator (ICD) therapy in primary prevention patients. However, only a few data are available for secondary prevention (SP) patients. The aim of this study was to evaluate whether these ICD programming would be effective in reducing ICD therapies in SP patients. We enrolled 65 SP patients under ICD or cardiac resynchronization therapy with the defibrillator programmed with the same setting (conventional setting). During follow-up, we changed detection rates in each zone; cycle length (CL) <=400 to <=370 ms for ventricular tachycardia (VT) zone, CL <=350 to <=320 ms for fast VT zone, CL <=300 to <=270 ms for ventricular fibrillation (VF) zone, and number of intervals to detect ventricular tachyarrhythmia in VF zone: 12-24. We retrospectively compared the incidences of ICD therapies, syncope, and hospitalization due to slow VT under the detection rate between both settings. Median follow-up periods were 5.0 (interquartile range 2.5-7.8) and 2.5 years (interquartile range 2.3-2.7) in conventional and strategic settings, respectively. The incidence of appropriate ATP and shock significantly decreased in strategic setting (conventional and strategic settings: 21.2 and 4.8 ATPs per year, respectively, OR 0.18, 95 % CI 0.06-0.54, p = 0.002, 26.1 and 7.8 shocks per year, respectively, OR 0.29, 95 % CI 0.09-0.88, p = 0.03). The incidence of overall inappropriate therapy significantly decreased (conventional and strategic settings: 17.6 and 2.8 therapies per year, respectively, OR 0.14, 95 % CI 0.05 0.44, p = 0.01). The incidence of syncope and slow VT was not significantly different between both settings. In conclusion, ICD programming-combined long detection interval with high-rate cutoff was effective in reducing appropriate shock and inappropriate therapy without increasing the incidence of syncope and slow VT in SP patients. PMID- 27259486 TI - The interplay of goal-driven and stimulus-driven influences on spatial orienting. AB - Search for a target stimulus among distractors is subject to both goal-driven and stimulus-driven influences. Variables that selectively modify these influences have shown strong interaction effects on saccade trajectories toward the target, suggesting the involvement of a shared spatial orienting mechanism. However, subsequent manual response times (RTs) have revealed additive effects, suggesting that different mechanisms are involved. In the present study, we tested the hypothesis that an interaction for RTs is obscured by preceding multisaccade trajectories, promoted by the continuous presence of distractors in the display. In two experiments, we compared a condition in which distractors were removed soon after the presentation of the search display to a standard condition in which distractors were not removed. The results showed additive goal-driven and stimulus-driven effects on RTs in the standard condition, but an interaction when distractors were removed. These findings support the view that both variables influence a shared spatial orienting mechanism. PMID- 27259487 TI - Psychosocial risk factors underlie the link between attention deficit hyperactivity symptoms and overweight at school entry. AB - The link between symptoms of attention deficit hyperactivity disorder (ADHD) and increased body weight is well established, while the underlying mechanisms are not yet clear. Since increased body weight and ADHD symptoms have been found to be associated with psychosocial risk factors in childhood, we analyzed whether the psychosocial risks explain the association between the two conditions. The sample consisted of 360 children (age range 6-7 years, 173 boys) attending the obligatory medical health exam before school entry. The childrens' height and weight were measured during the examination. ADHD symptoms were ascertained by parent-report questionnaires. Psychosocial risks were ascertained by a structured interview. The link between ADHD symptoms and body weight could be completely explained by cumulative psychosocial risks while controlling for gender, symptoms of depression/anxiety and oppositional defiant disorder of the child, maternal smoking during pregnancy, parental body mass index, and potential diagnosis of ADHD in the parents. In current models pertaining to the etiology of overweight/obesity and ADHD, chronic stress caused by psychosocial adversity is assumed to act as a trigger for these conditions. Psychosocial risks experienced during childhood may activate processes that specifically lead to the combined ADHD-overweight phenotype. PMID- 27259485 TI - Effects of anti-depressant treatments on FADD and p-FADD protein in rat brain cortex: enhanced anti-apoptotic p-FADD/FADD ratio after chronic desipramine and fluoxetine administration. AB - RATIONALE: Fas-associated death domain (FADD) is an adaptor of death receptors that can also induce anti-apoptotic actions through its phosphorylated form (p FADD). Activation of monoamine receptors, indirect targets of classic anti depressant drugs (ADs), reduced FADD and increased p-FADD and p-FADD/FADD ratio in brain. OBJECTIVES: To ascertain whether ADs, which indirectly regulate monoamine receptors, modulate FADD protein forms to promote anti-apoptotic actions. METHODS: The effects of selected norepinephrine transporter (NET), serotonin transporter (SERT), monoamine oxidase (MAO) inhibitors, atypical ADs, and electroconvulsive shock (ECS) or behavioral procedures (forced swim test, FST) on FADD forms and pro-survival FADD-like interleukin-1beta-converting enzyme inhibitory protein (FLIP-L) and phosphoprotein enriched in astrocytes of 15 kDa (p-PEA-15) contents were assessed in rat brain cortex by western blot analysis. RESULTS: Acute NET (e.g., nisoxetine) but not SERT (e.g., fluoxetine) inhibitors decreased cortical FADD (up to 37 %) and increased p-FADD/FADD ratio (up to 1.9 fold). Nisoxetine effects were prevented by alpha2-antagonist RX-821002, suggesting the involvement of presynaptic alpha2-autoreceptors. Immobility time in the FST correlated with increases of pro-apoptotic FADD and decreases of anti apoptotic p-FADD. The MAO-A/B inhibitor phenelzine decreased FADD (up to 33 %) and increased p-FADD (up to 65 %) and p-FADD/FADD (up to 2.4-fold). Other MAO inhibitors (clorgyline, Ro 41-1049, rasagiline), atypical ADs (ketamine and mirtazapine), or ECS did not modulate cortical FADD. Chronic (14 days) desipramine and fluoxetine, but not phenelzine, increased p-FADD (up to 59 %), p FADD/FADD ratio (up to 1.8-fold), and pro-survival p-PEA-15 (up to 46 %) in rat brain cortex. CONCLUSIONS: Multifunctional FADD protein, through an increased p FADD/FADD ratio, could participate in the mechanisms of anti-apoptotic actions induced by ADs. PMID- 27259489 TI - Photographing Determinants of Mental Health in Argentina Post-2002 Economic Crisis. PMID- 27259488 TI - The prospective usefulness of callous-unemotional traits and conduct disorder in predicting treatment engagement among detained girls. AB - Although treatment engagement (TE) is crucial for treatment success it is not well known how likely detained girls are to engage in treatment and what features may impede them from doing so. This study is the first to examine the prognostic usefulness of two features of potential interest, being callous-unemotional (CU) traits and conduct disorder (CD), in relation to TE. Detained girls and their parents (n = 75) were interviewed with the Diagnostic Interview Schedule for Children to assess CD, and completed the Antisocial Process Screening Device to assess CU traits dimensionally and categorically as in the new diagnostic and statistical manual of mental disorders, fifth edition (DSM-5) CU-based specifier. One to two months later, the girls reported how much they engaged in treatment. At the zero-order level, self-, but not parent-reported CU traits and CD were predictive of lower levels of TE. The incorporation of CU traits into a diagnosis of CD identified girls with lower levels of future TE, a finding that held across different informants. Of note, the aforementioned findings only became apparent when using a dimensional measure of CU traits, and not when using the categorical measure of CU traits currently included in DSM-5. This study showed that CU traits can help developing an understanding of what factors hinder TE among detained girls. Our findings also support recommendations to incorporate CU traits into the CD diagnosis, and suggest that dimensional approaches to do so may yield relevant information about future levels of TE. PMID- 27259490 TI - Global Mental Health. PMID- 27259491 TI - The Mental Health Education Gap among Primary Care Providers in Rural Nepal. AB - OBJECTIVE: In low- and middle-income countries, the majority of individuals with mental illness go untreated largely because of a severe shortage of mental health professionals. Global initiatives to close the mental health treatment gap focus on primary care providers delivering this care. For this to be effective, primary care providers require the skills to assess, diagnose, and treat patients with mental illness. METHODS: To assess primary care providers' training and experience in caring for mental health patients, the authors conducted five focus groups at three isolated district hospitals in rural Nepal where there was no access to mental health professionals. RESULTS: Primary care providers reported limited training, lack of knowledge and skills, and discomfort in delivering mental health care. CONCLUSION: To address the mental health education gap, primary care providers in Nepal, and perhaps other low- and middle-income countries, require more training during both undergraduate and graduate medical education. PMID- 27259492 TI - Erratum to: Waves of c-Fos and Arc Proteins Expression in Neuronal Populations of the Hippocampus in Response to a Single Episode of New Experience. PMID- 27259493 TI - Experimental Simulation of Traumatic Osteomyelitis in Rats. AB - A model of traumatic osteomyelitis in rats is created. The disease development was evaluated by bone marrow myelograms, results of scintigraphy, and histological studies. PMID- 27259494 TI - Ultrastructure of Cardiomyocytes and Blood Capillary Endotheliocytes in the Myocardium under Conditions of Experimental Mechanical Injury to the Heart. AB - We studied ultrastructural changes in cardiomyocytes and blood capillary endotheliocytes in the ventricular myocardium in response to mechanical injury of the heart of varying severity in Wistar rats. Acute alterative changes in cardiomyocyte and endotheliocyte ultrastructure indicate impairment of the energy producing, contractile, and protein-synthesizing functions of the cells after mechanical injury. These disorders play the key role in the development of acute contractile insufficiency of the myocardium in mechanical injury to the heart. PMID- 27259495 TI - Kinetic Chemiluminescence as a Method for Oxidative Stress Evaluation in Examinations of Patients with Type 2 Diabetes Mellitus. AB - We propose a new approach to evaluation of oxidative stress based on kinetic chemiluminescence: measurement of antioxidant and pro-oxidant activities of the plasma. The study included 50 patients with type 2 diabetes mellitus receiving peroral hypoglycemic therapy. In addition to the above parameters, the levels of TBA-reactive products, inflammation markers, clotting parameters, and biochemical values were studied. The new method provides information on oxidative stress in patients with type 2 diabetes mellitus irrespective of the clinical and laboratory values. The use of this method in complex with the clinical, laboratory, and instrumental studies allows comprehensive evaluation of patient's status for the diagnosis and choice of therapy. PMID- 27259496 TI - Peptide Regulation of Skin Fibroblast Functions during Their Aging In Vitro. AB - The effect peptides KE, KED, AED and AEDG on proliferation (Ki-67), regeneration and aging (CD98hc), apoptosis (caspase-3), and extracellular matrix remodeling (MMP-9) in skin fibroblasts during their aging in culture were studied by immunofluorescent confocal microscopy. All studied peptides inhibited MMP-9 synthesis that increases during aging of skin fibroblasts and enhanced the expression of Ki-67 and CD98hc that are less intensively synthesized during cell aging. Peptides AED and AEDG suppressed caspase-dependent apoptosis that increases during aging of cell cultures. PMID- 27259497 TI - A Model of Cadmium Uptake and Transport in Caco-2 Cells. AB - We created a physiologically substantiated kinetic model of cadmium transport and toxicity in intestinal cell model (Caco-2 cells). Transcriptome profiling of Caco 2 cells revealed high content of transporter DMT1 and ZIP14 and intensive expression of some calcium channels of the CACN family. The mathematical model describing three types of transporters, as well as intracellular cadmium binding with metallothionein and excretion through the basolateral membrane allowed us to construct cadmium uptake and transport curves that approximated the previously obtained experimental data. Using the proposed model, we determined toxic intracellular cadmium concentration leading to cell death and impairing the integrity of cell monolayer and described cadmium transport in this case. PMID- 27259498 TI - Effect of Factors Secreted by the Placenta on Phenotype of THP-1 Cells Cultured on a 3D Scaffold. AB - We studied the effects of secretory products of the placenta obtained from women with normal pregnancy and preeclampsia on the expression of surface markers by THP-1 cells cultured on a 3D Matrigel scaffold. Secretory products of third trimester placentas obtained from women with normal pregnancy reduced the relative number of THP-1 cells expressing CD54 and CD14 molecules and expression of CD14 and CD95 molecules by THP-1 cells in comparison with the effect of secretory products first trimester placentas. In parallel, the intensity of CD49d expression by THP-1 cells increased in the presence of secretory products of third trimester placentas in comparison with the first trimester. No differences in the expression of the studied molecules by THP-1 cells under the effect of placentas from women with physiological pregnancy and patients with preeclampsia were found. PMID- 27259499 TI - Antihypoxic and Neuroprotective Effects of Glial Cell-Derived Neurotrophic Factor (GDNF) in Cultures of Dissociated Hippocampal Cells under Conditions of Experimental Hypoxia. AB - We analyzed the effect of glial cell derived neurotrophic factor (GDNF) on changes in functional bioelectric and calcium activity in dissociated hippocampal cell cultures under conditions of modeled acute normobaric hypoxia in vitro. GDNF (1 ng/ml) partially neutralized the negative effects of hypoxia on cell survival and parameters of functional network activity. GDNF exhibited a pronounced anti hypoxic effect. PMID- 27259500 TI - Cervical elastography during pregnancy: a critical review of current approaches with a focus on controversies and limitations. AB - In normal pregnancy, the cervix functions as a protective mechanical barrier that must remain tight and closed. Premature remodeling and consecutive shortening occur in many cases of spontaneous preterm birth. Although the complex underlying physiology of normal and abnormal cervical remodeling is not fully understood, it is clear that cervical softening occurs prior to delivery, and inappropriate timing seems to be associated with preterm delivery. Also, degree of cervical softness is a component of the Bishop score currently used clinically to predict successful induction of labor. Therefore, the assessment of changes in cervical stiffness with ultrasound elastography techniques might be useful in the prediction of preterm delivery or successful induction of labor. Two different approaches for cervical elastography for quantitative determination of the physical properties of the pregnant cervix have been developed: strain elastography and shear wave elastography. Recently, several feasibility studies showed the reliability of these cervical elastography techniques for the prediction of preterm delivery and successful labor induction. In this review, we contrast strain elastography, which determines only relative values of tissue stiffness because the applied transducer pressure is unknown, with shear wave elastography, which provides, in principle at least, a more objective description of tissue softness. While more promising preliminary results involving these approaches to assessing cervical softness have been recently published, current limitations in technical implementation need to be addressed before elastography techniques will become clinically useful. We discuss these limitations and present challenges for future studies and equipment development. PMID- 27259501 TI - Chloroplasts: state of research and practical applications of plastome sequencing. AB - MAIN CONCLUSION: This review presents origins, structure and expression of chloroplast genomes. It also describes their sequencing, analysis and modification, focusing on potential practical uses and biggest challenges of chloroplast genome modification. During the evolution of eukaryotes, cyanobacteria are believed to have merged with host heterotrophic cell. Afterward, most of cyanobacterial genes from cyanobacteria were transferred to cell nucleus or lost in the process of endosymbiosis. As a result of these changes, a primary plastid was established. Nowadays, plastid genome (plastome) is almost always circular, has a size of 100-200 kbp (120-160 in land plants), and harbors 100-120 highly conserved unique genes. Plastids have their own gene expression system, which is similar to one of their cyanobacterial ancestors. Two different polymerases, plastid-derived PEP and nucleus-derived NEP, participate in transcription. Translation is similar to the one observed in cyanobacteria, but it also utilizes protein translation factors and positive regulatory mRNA elements absent from bacteria. Plastoms play an important role in genetic transformation. Transgenes are introduced into them either via gene gun (in undamaged tissues) or polyethylene glycol treatment (when protoplasts are targeted). Antibiotic resistance markers are the most common tool used for selection of transformed plants. In recent years, plastome transformation emerged as a promising alternative to nuclear transformation because of (1) high yield of target protein, (2) removing the risk of outcrossing with weeds, (3) lack of silencing mechanisms, and (4) ability to engineer the entire metabolic pathways rather than single gene traits. Currently, the main directions of such research regard: developing efficient enzyme, vaccine antigen, and biopharmaceutical protein production methods in plant cells and improving crops by increasing their resistance to a wide array of biotic and abiotic stresses. Because of that, the detailed knowledge of plastome structure and mechanism of functioning started to play a major role. PMID- 27259502 TI - Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome. AB - PURPOSE: Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. METHODS: Cross sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. RESULTS: AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. CONCLUSIONS: According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity. PMID- 27259503 TI - Enhanced cosyntropin stimulation test performance enabled by electronic medical record. AB - PURPOSE: To improve performance of the cosyntropin stimulation test (CST) used for diagnosis of adrenal-cortisol insufficiency by implementing an electronic medical record (EMR) system protocol. METHODS: We implemented a SmartForm protocol of the validated CST in our EMR system (CS-LinkTM, EPIC) system and compared medical staff test performance before and after protocol implementation. RESULTS: Correct performance of the CST improved significantly after EMR implementation. The number of correctly performed CSTs increased from 16.1 % before to 53.5 % after implementation (p < 0.0001) while those performed incorrectly and were uninterpretable decreased from 36.2 to 7.1 % (p < 0.0001). This performance improvement result in a calculated cost savings of $50,414 for every 100 tests performed. CONCLUSIONS: The EMR system is useful for guiding medical staff to accurately perform the CST, reduce the number of wasted tests, and maximize staff time and resources. PMID- 27259504 TI - Plasmonic Pd Nanoparticle- and Plasmonic Pd Nanorod-Decorated BiVO4 Electrodes with Enhanced Photoelectrochemical Water Splitting Efficiency Across Visible-NIR Region. AB - The photoelectrochemical (PEC) water splitting performance of BiVO4 is partially hindered by insufficient photoresponse in the spectral region with energy below the band gap. Here, we demonstrate that the PEC water splitting efficiency of BiVO4 electrodes can be effectively enhanced by decorating Pd nanoparticles (NPs) and nanorods (NRs). The results indicate that the Pd NPs and NRs with different surface plasmon resonance (SPR) features delivered an enhanced PEC water splitting performance in the visible and near-infrared (NIR) regions, respectively. Considering that there is barely no absorption overlap between Pd nanostructures and BiVO4 and the finite-difference time domain (FDTD) simulation indicating there are substantial energetic hot electrons in the vicinity of Pd nanostructures, the enhanced PEC performance of Pd NP-decorated BiVO4 and Pd NR decorated BiVO4 could both benefit from the hot electron injection mechanism instead of the plasmon resonance energy transfer process. Moreover, a combination of Pd NPs and NRs decorated on the BiVO4 electrodes leads to a broad-band enhancement across visible-NIR region. PMID- 27259505 TI - Quantitative assessment and characterization of glenoid bone loss in a spectrum of patients with glenohumeral osteoarthritis. AB - PURPOSE: Eccentric posterior bone loss and associated glenoid retroversion represent challenges to glenoid placement during total shoulder arthroplasty. This bone loss can lead to poor stability and perforation of the glenoid during arthroplasty. The purpose of this study was to evaluate the morphology of glenoid bone loss for a spectrum of osteoarthritis patients using 3D computed tomography imaging and simulation software. METHODS: This study included 29 patients with glenohumeral osteoarthritis treated with shoulder arthroplasty. Three-dimensional reconstruction of preoperative CT images was performed. Glenoid bone loss was measured at ten, vertically equidistant axial planes along the glenoid surface at four distinct anterior-posterior points on each plane. The images were fitted with modeled pegged glenoid implants to predict glenoid perforation. RESULTS: The 3D maps demonstrated greatest average bone loss posteriorly in the AP plane at the central axis of the glenoid in the SI plane. The average amount of bone loss was 3.85 mm. Walch A2 and B1 shoulders showed more central bone loss, while Walch B2 shoulders displayed more posterior and inferior bone loss. Patients with predicted peg perforation displayed significantly greater bone loss than those without predicted peg perforation (p = 0.037). Peg perforation was most common in Walch B2 shoulders occurring in the posterior direction involving the central and posterior-inferior peg. CONCLUSIONS: These data demonstrate an anatomic pattern of glenoid bone loss for different classes of glenohumeral arthritis. These findings can be used to develop various models of glenoid bone loss to guide surgeons, predict failures, and develop better glenoid implants. This study has been approved by the Cleveland Clinic IRB: Number 6235. PMID- 27259506 TI - The right patient for the right therapy: 13th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Mainz, Germany, May 11-13, 2015. PMID- 27259507 TI - Allocation of parathyroid adenoma and suspicious thyroid nodule by real-time 99mTc-MIBI SPECT/US fusion imaging. PMID- 27259508 TI - Rationale and design of the Early Sleeve gastrectomy In New Onset Diabetic Obese Patients (ESINODOP) trial. AB - No randomized clinical trials (RCTs) have yet evaluated the bariatric surgery's efficacy and safety in patients newly diagnosed with type 2 diabetes mellitus (T2DM). The aim of this multicenter RCT is to compare bariatric surgery, particularly laparoscopic sleeve gastrectomy (LSG), with conventional medical therapy (CMT) in obese patients (body mass index between 30 and 42 kg/m2) newly diagnosed with T2DM and without any diabetes-related complications at any stage. A total of 100 eligible patients will be randomized at a 1:1 ratio to undergo one of the two planned treatments and will be followed for at least 6 years after randomization. The main objective of the ESINODOP trial is to investigate the efficacy of LSG compared with CMT alone in inducing and maintaining a remission of T2DM (defined as HbA1c levels <=6.0 %, without active pharmacologic therapy after 1 year). The remission of T2DM will also be evaluated with the criteria provided by the American Diabetes Association (ADA), and the additional parameters such as adverse event rates, micro- and macrovascular complications, weight loss, gastrointestinal hormones, and quality of life will be compared. The study started on September 2015 and the planned recruitment period is 3 years. Patient recruitment and follow-up take place in the two diabetology and nutrition centers participating in the study, which are performed on a national basis. The ESINODOP trial is designed with the intent of comparing the efficacy of CMT alone to that of CMT in conjunction with LSG performed at the time of diabetes diagnosis in mildly obese diabetic patients. Currently, patients with these characteristics are not eligible for bariatric/metabolic surgery. PMID- 27259509 TI - Deteriorated high-fat diet-induced diabetes caused by pancreatic beta-cell specific overexpression of Reg3beta gene in mice. AB - Reg family proteins have long been implicated in islet beta-cell proliferation, survival, and regeneration. In our previous study, we reported that Reg3beta overexpression did not increase islet growth but prevented streptozotocin-induced islet damage by inducing specific genes. In order to explore its role in type 2 diabetes (T2D), we established high-fat diet (HFD)-induced obesity and diabetes in RIP-I/Reg3beta mice. Glucose and insulin tolerance tests, immunofluorescence for insulin, eIF2alpha, and GLUT2 in islets, Western blots on phosphorylated AMPKalpha and hepatic histology were performed. Both RIP-I/Reg3beta and wild-type mice gained weight rapidly and became hyperglycemic after 10 weeks on the HFD. However, the transgenic mice exhibited more significant acceleration in blood glucose levels, further deterioration of glucose intolerance and insulin resistance, and a lower intensity of insulin staining. Immunofluorescence revealed similar magnitude of islet compensation to a wild-type HFD. The normal GLUT2 distribution in the transgenic beta-cells was disrupted and the staining was obviously diminished on the cell membrane. HFD feeding also caused a further decrease in the level of AMPKalpha phosphorylation in the transgenic islets. Our results suggest that unlike its protective effect against T1D, overexpressed Reg3beta was unable to protect the beta-cells against HFD-induced damage. PMID- 27259510 TI - Antiproliferative effects of masitinib and imatinib against canine oral fibrosarcoma in vitro. AB - BACKGROUND: Canine oral fibrosarcoma (COF) is one of the most common oral tumors in dogs and carries a guarded prognosis due to a lack of effective systemic therapeutic options. Mastinib and imatinib are two commonly used tyrosine kinase inhibitors (TKIs) in veterinary oncology but their potential efficacy against COF is uncharacterized. To begin investigating the rationale for use of these TKIs against COF, the present study tested for the presence TKI targets PDGFR-alpha, PDGFR-beta, Kit, and VEGFR-2 and examined the in vitro effects on cell viability after TKI treatment alone or with doxorubicin. Immunohistochemistry for PDGFR alpha, PDGFR-beta, Kit, and VEGFR-2 was performed in 6 COF tumor biopsies. Presence of these same receptors within 2 COF cell lines was probed by reverse transcription-polymerase chain reaction and, for those with mRNA detected, confirmed via western blot. Effects on cell viability were assessed using an MTS assay after masitinib or imatinib treatment alone (0-100 MUM), or in combination with doxorubicin (0-3000 nM doxorubicin). Anti-PDGFRB siRNA knockdown was performed and the effect on cell viability quantified. RESULTS: Expression of the TKI targets evaluated was similar between the 2 COF cell lines and the 6 COF tumor biopsies: PDGFR-alpha and PDGFR-beta were detected in neoplastic cells from most COF tumor biopsies (5/6 and 6/6, respectively) and were present in both COF cell lines; KIT and KDR were not detected in any sample. Masitinib and imatinib IC50 values ranged from 7.9-33.4 MUM, depending on the specific TKI and cell line tested. The addition of doxorubicin resulted in synergistic cytotoxicity with both TKIs. Anti-PDGFRB siRNA transfection reduced PDGFR-beta protein expression by 77% and 67% and reduced cell viability by 24% (p < 0.0001) and 28% (0 = 0.0003) in the two cell lines, respectively. CONCLUSIONS: These results provide rationale for further investigation into the use of TKIs, possibly in combination with doxorubicin, as treatment options for COF. PMID- 27259511 TI - The association of wildfire smoke with respiratory and cardiovascular emergency department visits in Colorado in 2012: a case crossover study. AB - BACKGROUND: In 2012, Colorado experienced one of its worst wildfire seasons of the past decade. The goal of this study was to investigate the relationship of local PM2.5 levels, modeled using the Weather Research and Forecasting Model with Chemistry, with emergency department visits and acute hospitalizations for respiratory and cardiovascular outcomes during the 2012 Colorado wildfires. METHODS: Conditional logistic regression was used to assess the relationship between both continuous and categorical PM2.5 and emergency department visits during the wildfire period, from June 5(th) to July 6(th) 2012. RESULTS: For respiratory outcomes, we observed positive relationships between lag 0 PM2.5 and asthma/wheeze (1 h max OR 1.01, 95 % CI (1.00, 1.01) per 10 MUg/m(3); 24 h mean OR 1.04 95 % CI (1.02, 1.06) per 5 MUg/m(3)), and COPD (1 h max OR 1.01 95 % CI (1.00, 1.02) per 10 MUg/m(3); 24 h mean OR 1.05 95 % CI (1.02, 1.08) per 5 MUg/m(3)). These associations were also positive for 2-day and 3-day moving average lag periods. When PM2.5 was modeled as a categorical variable, bronchitis also showed elevated effect estimates over the referent groups for lag 0 24 h average concentration. Cardiovascular results were consistent with no association. CONCLUSIONS: We observed positive associations between PM2.5 from wildfire and respiratory diseases, supporting evidence from previous research that wildfire PM2.5 is an important source for adverse respiratory health outcomes. PMID- 27259512 TI - Comprehensive analysis of promoter-proximal RNA polymerase II pausing across mammalian cell types. AB - BACKGROUND: For many genes, RNA polymerase II stably pauses before transitioning to productive elongation. Although polymerase II pausing has been shown to be a mechanism for regulating transcriptional activation, the extent to which it is involved in control of mammalian gene expression and its relationship to chromatin structure remain poorly understood. RESULTS: Here, we analyze 85 RNA polymerase II chromatin immunoprecipitation (ChIP)-sequencing experiments from 35 different murine and human samples, as well as related genome-wide datasets, to gain new insights into the relationship between polymerase II pausing and gene regulation. Across cell and tissue types, paused genes (pausing index > 2) comprise approximately 60 % of expressed genes and are repeatedly associated with specific biological functions. Paused genes also have lower cell-to-cell expression variability. Increased pausing has a non-linear effect on gene expression levels, with moderately paused genes being expressed more highly than other paused genes. The highest gene expression levels are often achieved through a novel pause-release mechanism driven by high polymerase II initiation. In three datasets examining the impact of extracellular signals, genes responsive to stimulus have slightly lower pausing index on average than non-responsive genes, and rapid gene activation is linked to conditional pause-release. Both chromatin structure and local sequence composition near the transcription start site influence pausing, with divergent features between mammals and Drosophila. Most notably, in mammals pausing is positively correlated with histone H2A.Z occupancy at promoters. CONCLUSIONS: Our results provide new insights into the contribution of RNA polymerase II pausing in mammalian gene regulation and chromatin structure. PMID- 27259514 TI - The extremely rare vascular variant of a segmental duplicated uterine artery and its relevance for the interventionist and gynecologist: a case report. AB - BACKGROUND: Anatomic variants of the uterine artery are rare, with the absence of one of the uterine arteries presumably being the most abundant variant. A duplicated uterine artery is mentioned in the medical literature, but to the best of our knowledge, an angiographic study has never been published. A partially duplicated uterine artery is an extremely rare variant not previously mentioned in the literature, and it could lead to technical difficulties or cause problems in various gynecological interventions. CASE PRESENTATION: We present the case of a 45-year-old Caucasian woman with a uterine fibroid and typical fibroid-related symptoms who came to our department to get treated with fibroid embolization. During the procedure, angiography revealed a partial or segmental duplicated left uterine artery. This exceptionally rare anatomic variant proved to be beneficial for the safety of the embolization in our case; however, it is far more likely that such a variant would be unfavorable in some types of gynecological operative and minimally invasive techniques. CONCLUSIONS: Knowledge of the anatomic variant of a partially duplicated uterine artery is important, especially for gynecologists performing minimally invasive surgical procedures. PMID- 27259513 TI - The impact of body mass index on short-term surgical outcomes after laparoscopic hepatectomy, a retrospective study. AB - BACKGROUND: Surgeons may expect technical difficulties and worse outcomes when performing laparoscopic hepatectomy (LH) on obese patients. The aim of this study is to assess the impact of body mass index (BMI) on short-term surgical outcomes and to verify risk factors of conversion rate and complications of LH. METHODS: Data were collected from 551 patients who underwent attempted LH between August 1998 and April 2013. Patients were classified into four groups depending on their BMI according to the WHO's definition of obesity for Asia-Pacific region: underweight <18.5 kg/m(2) (Group1); normal 18.5-23.9 kg/m(2) (Group2); overweight 24-27.9 kg/m(2) (Group3); obese >= 28 kg/m(2) (Group4) respectively. Short-term surgical outcomes were compared across the BMI categories. Possible risk factors concerned conversion rate and complications were analyzed. RESULTS: The overall conversion rate of the 551 patients was 13.07 %. Conversion rate for Group 1, 2, 3, and 4 were 14.3 % (n = 5), 11.2 % (n = 38), 13.0 % (n = 19), and 34.5 % (n = 10) respectively. Patients within the obese group had a much higher conversion rate. The overall complications rate was 11.98 %, where the complication for Group 1, 2, 3, and 4 were 22.9 % (n = 8), 12.7 % (n = 43), 18.2 % (n = 12), and 10.3 % (n = 3) respectively. Patients within the underweight group had a higher complication rate, but it did not reach statistic difference. Obesity and surgical site of left lobe were independent risk factors of conversion. Age, abdominal surgery history, and type of left and right lobe resection were independent risk factors for complications. CONCLUSIONS: In China, obesity increases risk of conversion rate but it dose not affect surgical complications and other short-outcomes after LH. PMID- 27259515 TI - MRI during radiotherapy of glioblastoma : Does MRI allow for prognostic stratification? AB - AIM: To evaluate the role of magnetic resonance imaging (MRI) as a predictor for the clinical course in patients with glioblastoma. PATIENTS AND METHODS: In 64 patients with glioblastoma undergoing (chemo)radiotherapy MRI studies were obtained before radiation, after 30 gray (Gy), after 60 Gy and during follow-up. MRI findings were assigned to categories: definite progression, questionable progression, no change. Patients were followed clinically. RESULTS: At 30 Gy, 23 of 64 patients (36 %) demonstrated definite (dp; n = 15) or questionable (qp; n = 8) progression; in 41/64 (64 %) no change was found compared with preradiation MRI. After radiotherapy at 60 Gy, 26 of 64 (41 %) patients showed dp (n = 18) or qp (n = 8). In 2 cases with qp at the 30 Gy MRI, progress was unquestionable in the 60 Gy MRI study. In the 64 patients, 5 of the 60 Gy MRIs showed dp/qp after being classified as no change at the 30 Gy MRI, 2 of the 30 Gy MRIs showed qp, while the 60 Gy MRI showed tumour regression and 3 fulfilled the criteria for pseudoprogression during ongoing radiotherapy. The 30 Gy study allowed for prognostic stratification: dp/qp compared to stable patients showed median survival of 10.5 versus 20 months. CONCLUSION: MR follow-up after 30 Gy in patients undergoing (chemo)radiotherapy for glioblastoma allows prognostic appraisal. Pseudoprogression has to be taken into account, though rare in our setting. Based on these findings, early discussion of treatment modification is possible. PMID- 27259516 TI - Hypomineralised second primary molars: prevalence, pattern and associated co morbidities in 8- to 10-year-old children in Ile-Ife, Nigeria. AB - BACKGROUND: This study tries to determine the prevalence and co-morbidities associated with hypomineralised second primary molars (HSPM) in 8- to 10- year old children in Ile-Ife, Nigeria; and the co-existence of HSPM and Molar Incisor Hypomineralisation (MIH) in the study population. METHODS: This was a cross sectional study involving 8- to 10- year-old children in schooling in suburban Nigeria. Information was collected on the child's age, sex and socioeconomic status. Intraoral examination was conducted to determine the presence of HSPM, MIH, caries and the oral hygiene status of study participants. The severity of HSPM was also determined. The prevalence of HSPM, the association between HSPM, sex and socioeconomic status of study participants, the difference in the prevalence of caries and poor oral hygiene in children with and without HSPM, and the prevalence of HSPM and MIH co-morbidity were determined. RESULTS: Twenty seven of the 469 children examined (5.8 %) had HSPM. The tooth prevalence of HSPM was 3.9 %. There was no significant sex (p = 0.06), age (p = 0.41), and socioeconomic status (p = 0.67) differences between children with HSPM and without HSPM. More children with HSPM had caries (p <= 0.001) and poor oral hygiene (p = 0.01). Children with HSPM have increased odds having dental caries (AOR: 6.34; CI: 2.78-14.46; p = <0.001) and reduced odds of having good oral hygiene (AOR: 0.32; CI: 0.13-0.78; p = 0.01) when compare with children without HSPM. Also 77.8 % of children with HSPM also had MIH. CONCLUSION: The prevalence of HSPM in the study population is significantly high. The large number of children with HSPM and MIH also suggests that HSPM is a predisposing factor for MIH. The significantly higher proportion of children with HSPM who had caries and poor oral hygiene makes it imperative to institute screening programmes for HSPM/MIH in the study population. PMID- 27259517 TI - Possible misidentification of species in the Pseudomonas fluorescens lineage as Burkholderia pseudomallei and Francisella tularensis, and emended descriptions of Pseudomonas brenneri,Pseudomonas gessardii and Pseudomonas proteolytica. AB - Bacteria were isolated from an industrial water circuit in the Netherlands. These strains were identified using API 20 NE as possible, or likely, Burkholderia pseudomallei. With VITEK 2 some of these strains scored 'low discrimination' for Francisella tularensis, amongst others. A total of twenty-six strains were assigned to the species Pseudomonas brenneri, Pseudomonas gessardii or Pseudomonas proteolytica. Because of the possibility of misidentification of these environmental species as medical- and public-health relevant B. pseudomallei and F. tularensis, an emended description, based on tests results more customarily used in clinical laboratories, was suitable. For this reason, the strains in this study, including the type strains DSM 15294T, DSM 17152T and DSM 15321T, were subjected to a polyphasic identification procedure. This procedure consisted of multiple phenotypic tests, fatty acid analysis, 16S rDNA sequence analysis, matrix-assisted laser desorption ionization time-of-flight mass spectronomy and various species-specific molecular tests. Based on the results of the polyphasic procedures, the species descriptions of P. brenneri, P. gessardii and P. proteolytica have been emended. PMID- 27259518 TI - Calcium dependent plasticity applied to repetitive transcranial magnetic stimulation with a neural field model. AB - The calcium dependent plasticity (CaDP) approach to the modeling of synaptic weight change is applied using a neural field approach to realistic repetitive transcranial magnetic stimulation (rTMS) protocols. A spatially-symmetric nonlinear neural field model consisting of populations of excitatory and inhibitory neurons is used. The plasticity between excitatory cell populations is then evaluated using a CaDP approach that incorporates metaplasticity. The direction and size of the plasticity (potentiation or depression) depends on both the amplitude of stimulation and duration of the protocol. The breaks in the inhibitory theta-burst stimulation protocol are crucial to ensuring that the stimulation bursts are potentiating in nature. Tuning the parameters of a spike timing dependent plasticity (STDP) window with a Monte Carlo approach to maximize agreement between STDP predictions and the CaDP results reproduces a realistically-shaped window with two regions of depression in agreement with the existing literature. Developing understanding of how TMS interacts with cells at a network level may be important for future investigation. PMID- 27259520 TI - The effect of growth temperature on the nanoscale biochemical surface properties of Yersinia pestis. AB - Yersinia pestis, the causative agent of plague, has been responsible for several recurrent, lethal pandemics in history. Currently, it is an important pathogen to study owing to its virulence, adaptation to different environments during transmission, and potential use in bioterrorism. Here, we report on the changes to Y. pestis surfaces in different external microenvironments, specifically culture temperatures (6, 25, and 37 degrees C). Using nanoscale imaging coupled with functional mapping, we illustrate that changes in the surfaces of the bacterium from a morphological and biochemical standpoint can be analyzed simultaneously using atomic force microscopy. The results from functional mapping, obtained at a single cell level, show that the density of lipopolysaccharide (measured via terminal N-acetylglucosamine) on Y. pestis grown at 37 degrees C is only slightly higher than cells grown at 25 degrees C, but nearly three times higher than cells maintained at 6 degrees C for an extended period of time, thereby demonstrating that adaptations to different environments can be effectively captured using this technique. This nanoscale evaluation provides a new microscopic approach to study nanoscale properties of bacterial pathogens and investigate adaptations to different external environments. PMID- 27259519 TI - Loss of AP-2delta reduces retinal ganglion cell numbers and axonal projections to the superior colliculus. AB - BACKGROUND: AP-2delta is the most divergent member of the Activating Protein-2 (TFAP2) family of transcription factors. AP-2delta is restricted to specific regions of the CNS, including a subset of ganglion cells in the retina. Retinal ganglion cells (RGCs), the only output neurons of the retina, are responsible for transmitting the visual signal to the brain. RESULTS: AP-2delta knockout results in loss of Brn3c (Pou4f3) expression in AP-2delta -positive RGCs. While AP-2delta /- mice have morphologically normal retinas at birth, there is a significant reduction in retinal ganglion cell numbers by P21, after eye opening. Chromatin immunoprecipitation indicates that Brn3c is a target of AP-2delta in the retina. Using fluorochrome-conjugated cholera toxin subunit B to trace ganglion cell axons from the eye to the major visual pathways in the brain, we found 87 % and 32 % decreases in ipsilateral and contralateral projections, respectively, to the superior colliculus in AP-2delta-/- mice. In agreement with anatomical data, visually evoked responses recorded from the brain confirmed that retinal outputs to the brain are compromised. CONCLUSIONS: AP-2delta is important for the maintenance of ganglion cell numbers in the retina. Loss of AP-2delta alters retinal axonal projections to visual centers of the brain, with ipsilaterial projections to the superior colliculus being the most dramatically affected. Our results have important implications for integration of the visual signal at the superior colliculus. PMID- 27259522 TI - Association between neighbourhood air pollution concentrations and dispensed medication for psychiatric disorders in a large longitudinal cohort of Swedish children and adolescents. AB - OBJECTIVE: To investigate associations between exposure to air pollution and child and adolescent mental health. DESIGN: Observational study. SETTING: Swedish National Register data on dispensed medications for a broad range of psychiatric disorders, including sedative medications, sleeping pills and antipsychotic medications, together with socioeconomic and demographic data and a national land use regression model for air pollution concentrations for NO2, PM10 and PM2.5. PARTICIPANTS: The entire population under 18 years of age in 4 major counties. We excluded cohort members whose parents had dispensed a medication in the same medication group since the start date of the register. The cohort size was 552 221. MAIN OUTCOME MEASURES: Cox proportional hazards models to estimate HRs and their 95% CIs for the outcomes, adjusted for individual-level and group-level characteristics. RESULTS: The average length of follow-up was 3.5 years, with an average number of events per 1000 cohort members of ~21. The mean annual level of NO2 was 9.8 ug/m(3). Children and adolescents living in areas with higher air pollution concentrations were more likely to have a dispensed medication for a psychiatric disorder during follow-up (HR=1.09, 95% CI 1.06 to 1.12, associated with a 10 ug/m(3) increase in NO2). The association with NO2 was clearly present in 3 out of 4 counties in the study area; however, no statistically significant heterogeneity was detected. CONCLUSION: There may be a link between exposure to air pollution and dispensed medications for certain psychiatric disorders in children and adolescents even at the relatively low levels of air pollution in the study regions. The findings should be corroborated by others. PMID- 27259523 TI - Effectiveness of interventions to reduce ordering of thyroid function tests: a systematic review. AB - OBJECTIVES: To evaluate the effectiveness of behaviour changing interventions targeting ordering of thyroid function tests. DESIGN: Systematic review. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Database up to May 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies evaluating the effectiveness of behaviour change interventions aiming to reduce ordering of thyroid function tests. Randomised controlled trials (RCTs), non-randomised controlled studies and before and after studies were included. There were no language restrictions. STUDY APPRAISAL AND SYNTHESIS METHODS: 2 reviewers independently screened all records identified by the electronic searches and reviewed the full text of any deemed potentially relevant. Study details were extracted from the included papers and their methodological quality assessed independently using a validated tool. Disagreements were resolved through discussion and arbitration by a third reviewer. Meta-analysis was not used. RESULTS: 27 studies (28 papers) were included. They evaluated a range of interventions including guidelines/protocols, changes to funding policy, education, decision aids, reminders and audit/feedback; often intervention types were combined. The most common outcome measured was the rate of test ordering, but the effect on appropriateness, test ordering patterns and cost were also measured. 4 studies were RCTs. The majority of the studies were of poor or moderate methodological quality. The interventions were variable and poorly reported. Only 4 studies reported unsuccessful interventions but there was no clear pattern to link effect and intervention type or other characteristics. CONCLUSIONS: The results suggest that behaviour change interventions are effective particularly in reducing the volume of thyroid function tests. However, due to the poor methodological quality and reporting of the studies, the likely presence of publication bias and the questionable relevance of some interventions to current day practice, we are unable to draw strong conclusions or recommend the implementation of specific intervention types. Further research is thus justified. TRIAL REGISTRATION NUMBER: CRD42014006192. PMID- 27259524 TI - Prevalence of tinnitus and hyperacusis in children and adolescents: a systematic review. AB - OBJECTIVES: To systematically review studies of the epidemiology of tinnitus and hyperacusis in children and young people, in order to determine the methodological differences implicated in the variability of prevalence estimates and the influence of population characteristics on childhood tinnitus and hyperacusis. DATA SOURCES: Articles were retrieved from PubMed, EMBASE and Scopus databases and from the relevant reference lists using the methods described in the study protocol, which has previously been published. Reporting Items for Systematic Review (PRISMA) guidelines were followed. ELIGIBILITY CRITERIA: Studies addressing childhood prevalence, for example, children and young people aged 5-19 years. DATA SELECTION: 2 reviewers independently assessed the studies for eligibility, extracted data and assessed study consistency. Owing to the heterogeneity in the methodologies among the reported studies, only narrative synthesis of the results was carried out. RESULTS: Having identified 1032 publications, 131 articles were selected and 25 articles met the inclusion criteria and had sufficient methodological consistency to be included. Prevalence estimates of tinnitus range from 4.7% to 46% in the general paediatric population and among children with normal hearing, and from 23.5% to 62.2% of population of children with hearing loss. Reported prevalence ranged from 6% to 41.9% when children with hearing loss and normal hearing were both included. The prevalence of hyperacusis varied from 3.2% to 17.1%. CONCLUSIONS: Data on prevalence vary considerably according to the study design, study population and the research question posed. The age range of children studied was varied and a marked degree of variation between definitions (tinnitus, hyperacusis) and measures (severity, perception, annoyance) was observed. The lack of consistency among studies indicates the necessity of examining the epidemiology of tinnitus and hyperacusis in children and adolescents with a set of standardised criteria. TRIAL REGISTRATION NUMBER: CRD42014013456. PMID- 27259525 TI - Retrospective cross-sectional review of survival rates in critically ill children admitted to a combined paediatric/neonatal intensive care unit in Johannesburg, South Africa, 2013-2015. AB - OBJECTIVE: Report on survival to discharge of children in a combined paediatric/neonatal intensive care unit (PNICU). DESIGN AND SETTING: Retrospective cross-sectional record review. PARTICIPANTS: All children (medical and surgical patients) admitted to PNICU between 1 January 2013 and 30 June 2015. OUTCOME MEASURES: Primary outcome-survival to discharge. Secondary outcomes disease profiles and predictors of mortality in different age categories. RESULTS: There were 1454 admissions, 182 missing records, leaving 1272 admissions for review. Overall mortality rate was 25.7% (327/1272). Mortality rate was 41.4% (121/292) (95% CI 35.8% to 47.1%) for very low birthweight (VLBW) babies, 26.6% (120/451) (95% CI 22.5% to 30.5%) for bigger babies and 16.2% (86/529) (95% CI 13.1% to 19.3%) for paediatric patients. Risk factors for a reduced chance of survival to discharge in paediatric patients included postcardiac arrest (OR 0.21, 95% CI 0.09 to 0.49), inotropic support (OR 0.085, 95% CI 0.04 to 0.17), hypernatraemia (OR 0.16, 95% CI 0.04 to 0.6), bacterial sepsis (OR 0.32, 95% CI 0.16 to 0.65) and lower respiratory tract infection (OR 0.54, 95% CI 0.30 to 0.97). Major birth defects (OR 0.44, 95% CI 0.26 to 0.74), persistent pulmonary hypertension of the new born (OR 0.44, 95% CI 0.21 to 0.91), metabolic acidosis (OR 0.23, 95% CI 0.12 to 0.74), inotropic support (OR 0.23, 95% CI 0.12 to 0.45) and congenital heart defects (OR 0.29, 95% CI 0.13 to 0.62) predicted decreased survival in bigger babies. Birth weight (OR 0.997, 95% CI 0.995 to 0.999), birth outside the hospital (OR 0.21, 95% CI 0.05 to 0.84), HIV exposure (OR 0.54, 95% CI 0.30 to 0.99), resuscitation at birth (OR 0.49, 95% CI 0.25 to 0.94), metabolic acidosis (OR 0.25, 95% CI 0.10 to 0.60) and necrotising enterocolitis (OR 0.23, 95% CI 0.12 to 0.46) predicted poor survival in VLBW babies. CONCLUSIONS: Ongoing mortality review is essential to improve provision of paediatric critical care. PMID- 27259526 TI - Factors contributing to delayed diagnosis of cancer among Aboriginal people in Australia: a qualitative study. AB - BACKGROUND/OBJECTIVES: Delayed presentation of symptomatic cancer is associated with poorer survival. Aboriginal patients with cancer have higher rates of distant metastases at diagnosis compared with non-Aboriginal Australians. This paper examined factors contributing to delayed diagnosis of cancer among Aboriginal Australians from patient and service providers' perspectives. METHODS: In-depth, open-ended interviews were conducted in two stages (2006-2007 and 2011). Inductive thematic analysis was assisted by use of NVivo looking around delays in presentation, diagnosis and referral for cancer. PARTICIPANTS: Aboriginal patients with cancer/family members (n=30) and health service providers (n=62) were recruited from metropolitan Perth and six rural/remote regions of Western Australia. RESULTS: Three broad themes of factors were identified: (1) Contextual factors such as intergenerational impact of colonisation and racism and socioeconomic deprivation have negatively impacted on Aboriginal Australians' trust of the healthcare professionals; (2) health service related factors included low accessibility to health services, long waiting periods, inadequate numbers of Aboriginal professionals and high staff turnover; (3) patient appraisal of symptoms and decision-making, fear of cancer and denial of symptoms were key reasons patients procrastinated in seeking help. Elements of shame, embarrassment, shyness of seeing the doctor, psychological 'fear of the whole health system', attachment to the land and 'fear of leaving home' for cancer treatment in metropolitan cities were other deterrents for Aboriginal people. Manifestation of masculinity and the belief that 'health is women's domain' emerged as a reason why Aboriginal men were reluctant to receive health checks. CONCLUSIONS: Solutions to improved Aboriginal cancer outcomes include focusing on the primary care sector encouraging general practitioners to be proactive to suspicion of symptoms with appropriate investigations to facilitate earlier diagnosis and the need to improve Aboriginal health literacy regarding cancer. Access to health services remains a critical problem affecting timely diagnosis. PMID- 27259527 TI - Socioeconomic status and health-related quality of life among patients with prostate cancer 6 months after radical prostatectomy: a longitudinal analysis. AB - OBJECTIVES: To identify the associations between socioeconomic status (SES) and health-related quality of life (HRQOL) and the explanatory contribution of disease, patient and healthcare factors among patients with prostate cancer. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: In all, 246 patients from 2 hospitals in Hamburg/Germany who underwent radical prostatectomy completed a questionnaire shortly before discharge from hospital and again 6 months later. OUTCOME MEASURES: HRQOL as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C-30 including global quality of life, 5 functional scales and 9 symptom scales/items. Generalised estimating equations were calculated to analyse longitudinal data. RESULTS: Lower SES measured by income, education and occupational status is significantly associated with lower HRQOL 6 months after treatment. This especially holds true for the functional scales. After introducing disease, patient and healthcare factors, associations remain significant in the majority of cases. The explanatory contribution of patient factors such as comorbidity or psychosocial characteristics and of healthcare factors is slightly stronger than that of disease factors. CONCLUSIONS: We identified strong social inequalities in HRQOL among patients with prostate cancer 6 months after surgery, in Germany. The underlying causes could not be sufficiently identified, and further research regarding these associations and their explanatory factors is needed. PMID- 27259528 TI - Reporting of planned statistical methods in published surgical randomised trial protocols: a protocol for a methodological systematic review. AB - INTRODUCTION: Poor reporting can lead to inadequate presentation of data, confusion regarding research methodology used, selective reporting of results, and other misinformation regarding health research. One of the most recent attempts to improve quality of reporting comes from the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Group, which makes recommendations for the reporting of protocols. In this report, we present a protocol for a systematic review of published surgical randomised controlled trial (RCT) protocols, with the purpose of assessing the reporting quality and completeness of the statistical aspects. METHODS: We will include all published protocols of randomised trials that investigate surgical interventions. We will search MEDLINE, EMBASE, and CENTRAL for relevant studies. Author pairs will independently review all titles, abstracts, and full texts identified by the literature search, and extract data using a structured data extraction form. We will extract the following: year of publication, country, sample size, description of study population, description of intervention and control, primary outcome, important methodological qualities, and quality of reporting of planned statistical methods based on the SPIRIT guidelines. ETHICS AND DISSEMINATION: The results of this review will demonstrate the quality of statistical reporting of published surgical RCT protocols. This knowledge will inform recommendations to surgeons, researchers, journal editors and peer reviewers, and other knowledge users that focus on common deficiencies in reporting and how to rectify them. Ethics approval for this study is not required. We will disseminate the results of this review in peer-reviewed publications and conference presentations, and at a doctoral independent study of oral defence. PMID- 27259529 TI - Central venous Access device SeCurement And Dressing Effectiveness (CASCADE) in paediatrics: protocol for pilot randomised controlled trials. AB - INTRODUCTION: Paediatric central venous access devices (CVADs) are associated with a 25% incidence of failure. Securement and dressing are strategies used to reduce failure and complication; however, innovative technologies have not been evaluated for their effectiveness across device types. The primary aim of this research is to evaluate the feasibility of launching a full-scale randomised controlled efficacy trial across three CVAD types regarding CVAD securement and dressing, using predefined feasibility criteria. METHODS AND ANALYSIS: Three feasibility randomised, controlled trials are to be undertaken at the Royal Children's Hospital and the Lady Cilento Children's Hospital, Brisbane, Australia. CVAD securement and dressing interventions under examination compare current practice with sutureless securement devices, integrated securement dressings and tissue adhesive. In total, 328 paediatric patients requiring a peripherally inserted central catheter (n=100); non-tunnelled CVAD (n=180) and tunnelled CVAD (n=48) to be inserted will be recruited and randomly allocated to CVAD securement and dressing products. Primary outcomes will be study feasibility measured by eligibility, recruitment, retention, attrition, missing data, parent/staff satisfaction and effect size. CVAD failure and complication (catheter-associated bloodstream infection, local infection, venous thrombosis, occlusion, dislodgement and breakage) will be compared between groups. ETHICS AND DISSEMINATION: Ethical approval to conduct the research has been obtained. All dissemination will be undertaken using the CONSORT Statement recommendations. Additionally, the results will be sent to the relevant organisations which lead CVAD focused clinical practice guidelines development. TRIAL REGISTRATION NUMBERS: ACTRN12614001327673; ACTRN12615000977572; ACTRN12614000280606. PMID- 27259532 TI - The effect of buccal-lingual slot dimension size on third-order torque response. AB - Introduction: The focus of the presented study was to investigate the effect of buccal-lingual (B-L) orthodontic bracket slot dimension on third-order torque mechanics. Materials and methods: Three types of orthodontic brackets and two archwire sizes were considered. Ortho Classic H4 (0.026" B-L slot, passive), Ormco Damon Q (0.028" B-L slot, passive), and In-Ovation R (0.028" slot, active) brackets were tested using 0.017" * 0.025" and 0.019" * 0.025" beta-titanium archwires. An in vitro orthodontic torque simulator (OTS) was used to rotate archwires relative to a single bracket while recording forces and moments in three directions. For each bracket-archwire combination, a total of n = 47 samples were tested. Repeated measures analysis of variance between brackets was conducted for third-order torque values at 3 degrees increments between 9 degrees and 30 degrees during loading and unloading for each archwire size. Results: Statistically significant differences between H4 and Q brackets were only found for 0.017" * 0.025" archwires during loading, and 0.019" * 0.025" archwires during unloading. Conversely, differences between H4 and R brackets were found for both archwires during loading and unloading phases. Finally, when using a 0.017" * 0.025" archwire the H4 brackets reached the 5 Nmm threshold before R and Q brackets; however, there was little difference found when using a 0.019" * 0.025" archwire. Conclusions: The concept of using a smaller B-L bracket slot dimension in orthodontic treatment showed it may theoretically allow for more options, primarily using smaller archwires to correct third-order rotational misalignments. However, it is suspected that bracket material limitations and added loading on the door currently prevent this from being clinically applicable. PMID- 27259530 TI - Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence. AB - OBJECTIVES: Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. DESIGN: Retrospective cohort study. SETTING: Finnish healthcare registers. PARTICIPANTS: Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). OUTCOMES: Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. RESULTS: During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered >=80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). CONCLUSIONS: Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect. PMID- 27259531 TI - Effects of ionization on stability of 1-methylcytosine - DFT and PCM studies. AB - Consequences of ionization were studied by quantum-chemical methods (DFT and PCM) for 1-methylcytosine (MC)-a model of the nucleobase cytosine (C) connected with sugar in DNA. For calculations, three prototropic tautomers (one amino and two imino forms) and two imino zwitterions were considered, including conformational or configurational isomerism of exo heterogroups. Ionization and interactions between neighboring groups affect intramolecular proton-transfers, geometric and thermodynamic parameters, and electron delocalization for individual isomers. We discovered that an imino isomer is present in the isomeric mixture in the highest amount for positively ionized MC. Its contribution in neutral and negatively ionized MC is considerably smaller. Acid-base parameters for selected radical ions were estimated in the gas phase and compared to those of neutral MC. Gas phase acidity of radical cations is close to that of the conjugate acid of MC, and gas-phase basicity of radical anions is close to that of the conjugate base of MC. Various routes of amino-imino conversion between neutral and ionized isomers were considered. Energetic-barrier for intramolecular proton-transfer in MC is close to that in the parent system-formamidine. PMID- 27259533 TI - The contributions of handedness and working memory to episodic memory. AB - Past studies have independently shown associations of working memory and degree of handedness with episodic memory retrieval. The current study takes a step ahead by examining whether handedness and working memory independently predict episodic memory. In agreement with past studies, there was an inconsistent-handed advantage for episodic memory; however, this advantage was absent for working memory tasks. Furthermore, regression analyses showed handedness, and complex working memory predicted episodic memory performance at different times. Results are discussed in light of theories of episodic memory and hemispheric interaction. PMID- 27259534 TI - Prediction of non-muscle invasive bladder cancer outcomes assessed by innovative multimarker prognostic models. AB - BACKGROUND: We adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients. METHODS: Adapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up >10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico pathological prognosticators was evaluated using AUC-ROC and determination coefficient. RESULTS: Clinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (h (2)) of both outcomes was <1 % in NMIBC. CONCLUSIONS: We adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models. PMID- 27259535 TI - AMPK and HIF signaling pathways regulate both longevity and cancer growth: the good news and the bad news about survival mechanisms. AB - The AMP-activated protein kinase (AMPK) and hypoxia-inducible factor (HIF) signaling pathways are evolutionarily-conserved survival mechanisms responding to two fundamental stresses, energy deficiency and/or oxygen deprivation. The AMPK and HIF pathways regulate the function of a survival network with several transcription factors, e.g. FOXO, NF-kappaB, NRF2, and p53, as well as with protein kinases and other factors, such as mTOR, ULK1, HDAC5, and SIRT1. Given that AMPK and HIF activation can enhance not only healthspan and lifespan but also cancer growth in a context-dependent manner; it seems that cancer cells can hijack certain survival factors to maintain their growth in harsh conditions. AMPK activation improves energy metabolism, stimulates autophagy, and inhibits inflammation, whereas HIF-1alpha increases angiogenesis and helps cells to adapt to severe conditions. First we will review how AMPK and HIF signaling mechanisms control the function of an integrated survival network which is able not only to improve the regulation of longevity but also support the progression of tumorigenesis. We will also describe distinct crossroads between the regulation of longevity and cancer, e.g. specific regulation through the AMPKalpha and HIF alpha isoforms, the Warburg effect, mitochondrial dynamics, and cellular senescence. PMID- 27259536 TI - The effects of CO2 and nutrient fertilisation on the growth and temperature response of the mangrove Avicennia germinans. AB - In order to understand plant responses to both the widespread phenomenon of increased nutrient inputs to coastal zones and the concurrent rise in atmospheric CO2 concentrations, CO2-nutrient interactions need to be considered. In addition to its potential stimulating effect on photosynthesis and growth, elevated CO2 affects the temperature response of photosynthesis. The scarcity of experiments testing how elevated CO2 affects the temperature response of tropical trees hinders our ability to model future primary productivity. In a glasshouse study, we examined the effects of elevated CO2 (800 ppm) and nutrient availability on seedlings of the widespread mangrove Avicennia germinans. We assessed photosynthetic performance, the temperature response of photosynthesis, seedling growth and biomass allocation. We found large synergistic gains in both growth (42 %) and photosynthesis (115 %) when seedlings grown under elevated CO2 were supplied with elevated nutrient concentrations relative to their ambient growing conditions. Growth was significantly enhanced under elevated CO2 only under high nutrient conditions, mainly in above-ground tissues. Under low-nutrient conditions and elevated CO2, root volume was more than double that of seedlings grown under ambient CO2 levels. Elevated CO2 significantly increased the temperature optimum for photosynthesis by ca. 4 degrees C. Rising CO2 concentrations are likely to have a significant positive effect on the growth rate of A. germinans over the next century, especially in areas where nutrient availability is high. PMID- 27259537 TI - Somatic mutations in histiocytic sarcoma identified by next generation sequencing. AB - Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities. PMID- 27259538 TI - Comparison of parasitic mite retrieval methods in a population of community cats. AB - Objectives This study compared methods of mite retrieval from community cats in the Ohio River Valley region of the USA and determined incidence of parasitic mites in this region. Methods In total, 493 community cats were humanely trapped and anesthetized for a trap-neuter-return program. Cats received a dermatologic examination, ear swabs, superficial skin scraping, flea combing, acetate tape preparation and feces collection. All samples were examined microscopically. Large volumes of hair and scale from flea combing were dissolved in 10% potassium hydroxide and centrifuged with Sheather's solution. Fecal samples were mixed with Sheather's solution, filtered and centrifuged. Results Ear swabs were significantly ( P <0.05) better than other methods for finding chigger mites and Otodectes cynotis, and skin scraping was significantly better than ear swabs for finding Cheyletiella species. Only cats with O cynotis had clinical lesions. Mites remained identifiable for 6 months at room temperature. Mite incidence rates were as follows: Notoedres cati (1/493 cats), 0.002 (95% confidence interval [CI] 0-0.006); Lynxacarus radovskyi (2/493 cats), 0.004 (95% CI 0-0.01); Demodex gatoi (5/493 cats), 0.01 (95% CI 0.001-0.019); chigger mites (10/493 cats), 0.02 (95% CI 0.008-0.033); Cheyletiella species (12/493 cats), 0.024 (95% CI 0.011-0.038); and O cynotis (124/493 cats), 0.252 (95% CI 0.213-0.29). Conclusions and relevance Ear swabs are recommended when O cynotis or chigger mites are suspected. Skin scraping is more likely to yield positive results than ear swabs, but was not significantly better than acetate tape preparations, flea combing or fecal flotation for finding Cheyletiella species. Mites can remain identifiable for prolonged periods at room temperature. With the exception of O cynotis, the incidence of feline parasitic mites in the Ohio River Valley region of the USA is low; however, D gatoi and L radovskyi were present in the area and should be considered in cats with dermatologic disease attributable to them. In this population of community cats, asymptomatic carriage of mites was common. PMID- 27259539 TI - Designing robust watermark barcodes for multiplex long-read sequencing. AB - Motivation: To attain acceptable sample misassignment rates, current approaches to multiplex single-molecule real-time sequencing require upstream quality improvement, which is obtained from multiple passes over the sequenced insert and significantly reduces the effective read length. In order to fully exploit the raw read length on multiplex applications, robust barcodes capable of dealing with the full single-pass error rates are needed. Results: We present a method for designing sequencing barcodes that can withstand a large number of insertion, deletion and substitution errors and are suitable for use in multiplex single molecule real-time sequencing. The manuscript focuses on the design of barcodes for full-length single-pass reads, impaired by challenging error rates in the order of 11%. The proposed barcodes can multiplex hundreds or thousands of samples while achieving sample misassignment probabilities as low as 10-7 under the above conditions, and are designed to be compatible with chemical constraints imposed by the sequencing process. Availability and Implementation: Software tools for constructing watermark barcode sets and demultiplexing barcoded reads, together with example sets of barcodes and synthetic barcoded reads, are freely available at www.cifasis-conicet.gov.ar/ezpeleta/NS-watermark . Contact: ezpeleta@cifasis-conicet.gov.ar. PMID- 27259541 TI - MetaFast: fast reference-free graph-based comparison of shotgun metagenomic data. AB - MOTIVATION: High-throughput metagenomic sequencing has revolutionized our view on the structure and metabolic potential of microbial communities. However, analysis of metagenomic composition is often complicated by the high complexity of the community and the lack of related reference genomic sequences. As a start point for comparative metagenomic analysis, the researchers require efficient means for assessing pairwise similarity of the metagenomes (beta-diversity). A number of approaches were used to address this task, however, most of them have inherent disadvantages that limit their scope of applicability. For instance, the reference-based methods poorly perform on metagenomes from previously unstudied niches, while composition-based methods appear to be too abstract for straightforward interpretation and do not allow to identify the differentially abundant features. RESULTS: We developed MetaFast, an approach that allows to represent a shotgun metagenome from an arbitrary environment as a modified de Bruijn graph consisting of simplified components. For multiple metagenomes, the resulting representation is used to obtain a pairwise similarity matrix. The dimensional structure of the metagenomic components preserved in our algorithm reflects the inherent subspecies-level diversity of microbiota. The method is computationally efficient and especially promising for an analysis of metagenomes from novel environmental niches. AVAILABILITY AND IMPLEMENTATION: Source code and binaries are freely available for download at https://github.com/ctlab/metafast The code is written in Java and is platform independent (tested on Linux and Windows x86_64). CONTACT: ulyantsev@rain.ifmo.ru SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27259540 TI - UniCon3D: de novo protein structure prediction using united-residue conformational search via stepwise, probabilistic sampling. AB - MOTIVATION: Recent experimental studies have suggested that proteins fold via stepwise assembly of structural units named 'foldons' through the process of sequential stabilization. Alongside, latest developments on computational side based on probabilistic modeling have shown promising direction to perform de novo protein conformational sampling from continuous space. However, existing computational approaches for de novo protein structure prediction often randomly sample protein conformational space as opposed to experimentally suggested stepwise sampling. RESULTS: Here, we develop a novel generative, probabilistic model that simultaneously captures local structural preferences of backbone and side chain conformational space of polypeptide chains in a united-residue representation and performs experimentally motivated conditional conformational sampling via stepwise synthesis and assembly of foldon units that minimizes a composite physics and knowledge-based energy function for de novo protein structure prediction. The proposed method, UniCon3D, has been found to (i) sample lower energy conformations with higher accuracy than traditional random sampling in a small benchmark of 6 proteins; (ii) perform comparably with the top five automated methods on 30 difficult target domains from the 11th Critical Assessment of Protein Structure Prediction (CASP) experiment and on 15 difficult target domains from the 10th CASP experiment; and (iii) outperform two state-of the-art approaches and a baseline counterpart of UniCon3D that performs traditional random sampling for protein modeling aided by predicted residue residue contacts on 45 targets from the 10th edition of CASP. AVAILABILITY AND IMPLEMENTATION: Source code, executable versions, manuals and example data of UniCon3D for Linux and OSX are freely available to non-commercial users at http://sysbio.rnet.missouri.edu/UniCon3D/ CONTACT: chengji@missouri.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27259542 TI - Group-combined P-values with applications to genetic association studies. AB - MOTIVATION: In large-scale genetic association studies with tens of hundreds of single nucleotide polymorphisms (SNPs) genotyped, the traditional statistical framework of logistic regression using maximum likelihood estimator (MLE) to infer the odds ratios of SNPs may not work appropriately. This is because a large number of odds ratios need to be estimated, and the MLEs may be not stable when some of the SNPs are in high linkage disequilibrium. Under this situation, the P value combination procedures seem to provide good alternatives as they are constructed on the basis of single-marker analysis. RESULTS: The commonly used P value combination methods (such as the Fisher's combined test, the truncated product method, the truncated tail strength and the adaptive rank truncated product) may lose power when the significance level varies across SNPs. To tackle this problem, a group combined P-value method (GCP) is proposed, where the P values are divided into multiple groups and then are combined at the group level. With this strategy, the significance values are integrated at different levels, and the power is improved. Simulation shows that the GCP can effectively control the type I error rates and have additional power over the existing methods-the power increase can be as high as over 50% under some situations. The proposed GCP method is applied to data from the Genetic Analysis Workshop 16. Among all the methods, only the GCP and ARTP can give the significance to identify a genomic region covering gene DSC3 being associated with rheumatoid arthritis, but the GCP provides smaller P-value. AVAILABILITY AND IMPLEMENTATION: http://www.statsci.amss.ac.cn/yjscy/yjy/lqz/201510/t20151027_313273.html CONTACT: liqz@amss.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27259543 TI - DBSI server: DNA binding site identifier. AB - : Protein-nucleic acid interactions are among the most important intermolecular interactions in the regulation of cellular events. Identifying residues involved in these interactions from protein structure alone is an important challenge. Here we introduce the webserver interface to DNA Binding Site Identifier (DBSI), a powerful structure-based SVM model for the prediction and visualization of DNA binding sites on protein structures. DBSI has been shown to be a top-performing model to predict DNA binding sites on the surface of a protein or peptide and shows promise in predicting RNA binding sites. AVAILABILITY AND IMPLEMENTATION: Server is available at http://dbsi.mitchell-lab.org CONTACT: jcmitchell@wisc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27259544 TI - Three operational taxonomic units of Eimeria are common in Nigerian chickens and may undermine effective molecular diagnosis of coccidiosis. AB - BACKGROUND: Chicken is fast becoming the world's most consumed meat. As a consequence poultry health is more important now than ever before, with pathogens of chickens recognised as serious threats to food security. One such threat are Eimeria species parasites, protozoa which can cause the disease coccidiosis. Eimeria can compromise economic poultry production and chicken welfare, and have serious consequences for poor livestock keepers. Seven Eimeria species that infect chickens are recognised with a global enzootic distribution. More recently three cryptic Operational Taxonomic Units (OTUx, y and z) have been described in populations of Eimeria recovered from chickens in Australia. Two of the three OTUs have also been detected in sub-Saharan Africa, but their occurrence, pathology and the risk they pose is largely unknown. RESULTS: Nigeria has witnessed a dramatic expansion in poultry production and is now the largest poultry producer in Africa. Here, faecal samples collected from nine of 12 commercial chicken farms sampled in Kaduna state, Nigeria, were found to contain eimerian oocysts. After amplification by in vivo propagation all three cryptic OTU genotypes were detected using polymerase chain reaction (PCR), including OTUy for the first time outside of Australia. Comparison with a widely used, established Eimeria species-specific PCR assay revealed failure to detect the OTU genotypes. CONCLUSIONS: All three of the Eimeria OTU genotypes appear to be common in north-western Nigeria. The failure of a leading species-specific molecular assay to detect these genotypes indicates a risk of false negative Eimeria diagnosis when using molecular tools and suggests that the spatial occurrence of each OTU may be far wider than has been recognised. The risk posed by these novel genotypes is unknown, but it is clear that a better understanding of Eimeria occurrence is required together with the validation of effective diagnostics. PMID- 27259545 TI - Appropriateness of no-fault compensation for research-related injuries from an African perspective: an appeal for action by African countries. AB - Compensation for research-related injuries (RRIs) remains a challenge in the current environment of global collaborative biomedical research as exemplified by the continued reluctance of the US government, a major player in international biomedical research, to enact regulation for mandatory compensation for RRIs. This stance is in stark contrast to the mandatory compensation policies adopted by other democracies like the European Union (EU) countries. These positions taken by the USA and the EU create a nexus of confusion when research is exported to low-income and middle-income countries which have no laws guiding compensation for RRIs. In this paper, we begin by exploring the background to policies concerning RRIs, how they reflect on the traditional dispute resolution mechanisms in African societies, and how this compares with the no-fault compensation model. We then explore the underlying African ethical framework of Ubuntu in the sub-Saharan region, guiding traditional practices of dispute resolution and compensation, and how this framework can help to form the moral justification for no-fault compensation as the preferred compensation model for RRIs for African countries. Finally, we call upon countries in the African Union (AU), to adopt a no-fault policy for compensation of RRIs, and enact it into a regulatory requirement for insurance-based no-fault compensation for biomedical research, which will then be enforced by member states of the AU. PMID- 27259546 TI - When to start paediatric testing of the adult HIV cure research agenda? AB - Ethical guidelines recommend that experimental interventions should be tested in adults first before they are tested and approved in children. Some challenge this paradigm, however, and recommend initiating paediatric testing after preliminary safety testing in adults in certain cases. For instance, commentators have argued for accelerated testing of HIV vaccines in children. Additionally, HIV cure research on the use of very early therapy (VET) in infants, prompted in part by the Mississippi baby case, is one example of a strategy that is currently being tested in infants before it has been well tested in adults. Because infants' immune systems are still developing, the timing of HIV transmission is easier to identify in infants than in adults, and infants who receive VET might never develop the viral reservoirs that make HIV so difficult to eradicate, infants may be uniquely situated to achieve HIV cure or sustained viral remission. Several commentators have now argued for earlier initiation of HIV cure interventions other than (or in addition to) VET in children. HIV cure research is therefore a good case for re-examining the important question of when to initiate paediatric research. I will argue that, despite the potential for HIV cure research to benefit children and the scientific value of involving children in this research, the HIV cure agenda should not accelerate the involvement of children for the following reasons: HIV cure research is highly speculative, risky, aimed at combination approaches and does not compare favourably with the available alternatives. I conclude by drawing general implications for the initiation of paediatric testing, including that interventions that have to be used in combination with others and cures for chronic diseases may not be valuable enough to justify early paediatric testing. PMID- 27259547 TI - [Sigmoid colon diverticulitis : Treatment modalities 2011-2013]. AB - INTRODUCTION: Diverticulosis is a relevant disease in Germany with a prevalence of over 60 % in patients aged >=70 years. The S2k guidelines for the treatment of diverticulosis were recently published. Systematic epidemiological data on treatment modalities do not exist. METHODS: Analysis of in-hospital treatment modalities for diverticulosis based on data from the Federal Office of Statistics. RESULTS: Approximately 130,000 inpatient cases of diverticulosis are treated in Germany per year. Approximately 25 % undergo surgery and of these slightly under 50 % (12,000 procedures) are carried out by laparoscopy. The complication rates are 18 % in a best case scenario and up to 85 % in a worst case scenario. A stage-adjusted classification of treatment modalities based on data from the Federal Office of Statistics is currently practically impossible. CONCLUSION: To enable stage-adjusted epidemiological analysis of diverticulosis, a standardized and transparent documentation system enabling systematic analysis is necessary, which does not currently exist (e. g. ICD 10 coding); moreover, information on conservative and interventional treatment options are not included in the operations and procedures key (OPS) coding system. PMID- 27259548 TI - [Endoscopic vacuum therapy for Boerhaave's syndrome]. AB - INTRODUCTION: Operative and interventional treatment of Boerhaave's syndrome include closure of the esophageal defect and drainage of the septic focus. Initial reports on the use of endoscopic vacuum therapy (EVT) of Boerhaave's syndrome are now available. This article describes the experiences gained from the clinical application in two patients using this new surgical endoscopic procedure. The current literature regarding treatment of Boerhaave's syndrome is presented. MATERIAL AND METHODS: Open-pore drainage is endoscopically placed either through the transmural defect in the extraluminal wound cavity (intracavitary EVT) or overlapping the defect into the esophageal lumen (intraluminal EVT). The application of a negative pressure results in active drainage directed to the lumen and simultaneously in defect closure. Through these therapeutic measures the perforation defect and the septic focus can be healed. Open-pore drains are manufactured from drainage tubes and open-pore foam or an open-pore film. RESULTS: In both patients the distal esophageal perforation defects were completely healed using EVT. In 1 patient the treatment with EVT alone lasted 8 days. For the second patient EVT was combined with an open thoracotomy for decortication of pleural empyema. The treatment with EVT lasted 23 days and 1 cycle of EVT was carried out with an new open-pore film drainage (OFD). Surgical treatment to close the defect or an esophageal resection was not necessary for both patients. In the currently available studies and single case reports of ETV for Boerhaave's syndrome, 11 patients (84 %) of a total of 13 patients have been successfully treated. CONCLUSION: First clinical experiences have demonstrated that with EVT draining of the septic focus and closure of the Boerhaave defect at the gastroesophageal junction can be achieved. The EVT is an organ-preserving endoscopic surgical treatment, which can be an alternative and complementary to traditional surgery. PMID- 27259549 TI - [Erratum to: Report of 12 years experience in the surgical treatment of 286 paraesophageal hernias]. PMID- 27259551 TI - Improving end of life care in care homes; an evaluation of the six steps to success programme. AB - BACKGROUND: There are approximately 426,000 people residing within care homes in the UK. Residents often have complex trajectories of dying, which make it difficult for staff to manage their end-of-life care. There is growing recognition for the need to support care homes staff in the care of these residents with increased educational initiatives. One educational initiative is The Six Steps to Success programme. METHOD: In order to evaluate the implementation of Six Steps with the first cohort of care homes to complete the end-of-life programme in the North West of England., a pragmatic evaluation methodology was implemented in 2012-2013 using multiple methods of qualitative data collection; online questionnaire with facilitators (n = 16), interviews with facilitators (n = 9) and case studies of care homes that had completed the programme (n = 6). The evaluation explored the implementation approach and experiences of the programme facilitators and obtain a detailed account of the impact of Six Steps on individual care homes. Based upon the National Health Service (NHS) End of Life Care (EoLC) Programme, The Route to Success in EoLC - Achieving Quality in Care Homes. RESULTS: The programme was flexibly designed so that it could be individually tailored to the geographical location and the individual cohort requirements. Facilitators provided comprehensive and flexible support to care homes. Challenges to programme success were noted as; lack of time allocated to champions to devote to additional programme work, inappropriate staff selected as 'Champions' and staff sickness/high staff turnover presented challenges to embedding programme values. Benefits to completing the programme were noted as; improvement in Advance Care Planning, improved staff communication/confidence when dealing with multi-disciplinary teams, improved end of-life processes/documentation and increased staff confidence through acquisition of new knowledge and new processes. CONCLUSIONS: The findings suggested an overall positive impact from the programme. This flexibly designed programme continues to be dynamic, iteratively amended and improved which may affect the direct transferability of the results to future cohorts. PMID- 27259553 TI - The values of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting 30 day mortality in patients with acute pulmonary embolism. AB - BACKGROUND: vAcute pulmonary embolism (PE) is a life threatening disease. The treatment options depend on the severity of the disease and the mortality varies widely depending on the severity of the condition. It is important to identify patients who are at high risk of mortality. The aim of the present study was to explore the prognostic alues of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) for 30-day mortality in patients with acute PE. METHODS: The study included 321 patients admitted to our university hospital between January 2013 and May 2015 with the diagnosis of acute PE. Multivariable risk models were developed to assess the predictive values of the NLR and PLR for 30-day mortality. Discrimination was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Two hundred forty-eight patients met our selection criteria. Twenty of them died within 30 days of hospital admission. NLR was found to be an independent predicator after other confounding factors were adjusted in the model. For 1 unit of increase of NLR, the risk of 30-day mortality rose about 13 % (OR = 1.13,95 % CI: 1.04-1.23). The area under ROC for NLR is 0.79 (95 %CI: 0.703-0.880). PLR was associated with 30-day mortality in univariate analysis but the predicative ability diminished with inclusion of other predicators in multivariable model. CONCLUSIONS: NLR is readily available predicator for short-term mortality. It could be a useful indicator for identifying high risk population and guiding clinical management of acute PE. PMID- 27259552 TI - Antibiotic treatment for intermittent bladder catheterisation with once daily prophylaxis (the AnTIC study): Study protocol for a randomised controlled trial. AB - BACKGROUND: Clean intermittent self-catheterisation is an important management option for people who cannot empty their bladder effectively. Recurrent urinary tract infections are common in these patients. Data from recent studies suggest that antibiotic prophylaxis may be beneficial in reducing infection risk, but the effectiveness of this intervention remains uncertain. METHODS/DESIGN: This is a 52-site, patient randomised superiority trial set in routine care comparing an experimental strategy of once daily antibiotic prophylaxis for 12 months against a control strategy of no prophylaxis in people who carry out self-catheterisation and suffer recurrent urinary tract infections. The primary outcome is number of urinary tract infections during a 12-month treatment period. Both groups will otherwise receive usual care including on demand treatment courses of antibiotics for urinary tract infection. Participants and their clinicians will not be blinded to the allocated intervention, but central trial staff managing and analysing trial data will, as far as possible, be unaware of participant allocation. The analysis will follow intention-to-treat principles. DISCUSSION: This trial was commissioned and funded by the United Kingdom National Health Service following prioritisation of the research question by the National Institute for Health and Care Excellence. TRIAL REGISTRATION: ISRCTN67145101 EUDRACT2013-002556-32. Registered on 25 October 2013. PMID- 27259554 TI - Low vapour pressure deficit affects nitrogen nutrition and foliar metabolites in silver birch. AB - Air humidity indicated as vapour pressure deficit (VPD) is directly related to transpiration and stomatal function of plants. We studied the effects of VPD and nitrogen (N) supply on leaf metabolites, plant growth, and mineral nutrition with young micropropagated silver birches (Betula pendula Roth.) in a growth chamber experiment. Plants that were grown under low VPD for 26 d had higher biomass, larger stem diameter, more leaves, fewer fallen leaves, and larger total leaf area than plants that were grown under high VPD. Initially, low VPD increased height growth rate and stomatal conductance; however, the effect was transient and the differences between low and high VPD plants became smaller with time. Metabolic adjustment to low VPD reflected N deficiency. The concentrations of N, iron, chlorophyll, amino acids, and soluble carbohydrates were lower and the levels of starch, quercetin glycosides, and raffinose were higher in the leaves that had developed under low VPD compared with high VPD. Additional N supply did not fully overcome the negative effect of low VPD on nutrient status but it diminished the effects of low VPD on leaf metabolism. Thus, with high N supply, the glutamine to glutamate ratio and starch production under low VPD became comparable with the levels under high VPD. The present study demonstrates that low VPD affects carbon and nutrient homeostasis and modifies N allocation of plants. PMID- 27259550 TI - Mesenchymal stem cells in cardiac regeneration: a detailed progress report of the last 6 years (2010-2015). AB - Mesenchymal stem cells have been used for cardiovascular regenerative therapy for decades. These cells have been established as one of the potential therapeutic agents, following several tests in animal models and clinical trials. In the process, various sources of mesenchymal stem cells have been identified which help in cardiac regeneration by either revitalizing the cardiac stem cells or revascularizing the arteries and veins of the heart. Although mesenchymal cell therapy has achieved considerable admiration, some challenges still remain that need to be overcome in order to establish it as a successful technique. This in depth review is an attempt to summarize the major sources of mesenchymal stem cells involved in myocardial regeneration, the significant mechanisms involved in the process with a focus on studies (human and animal) conducted in the last 6 years and the challenges that remain to be addressed. PMID- 27259556 TI - Flavisolibacter tropicus sp. nov., isolated from tropical soil. AB - A Gram-stain-negative, non-motile, deep yellow, rod-shaped bacterium, designated strain LCS9T, was isolated from a soil sample at the tropical zone within the Ecorium of the National Institute of Ecology in Seocheon, central-western Korea. 16S rRNA gene sequence analysis showed that strain LCS9T clustered with members of the genus Flavisolibacter of the family Chitinophagaceae, phylum Bacteroidetes. Sequence similarities between strain LCS9T and the type strains of the genus Flavisolibacter ranged from 94.6 to 94.9 %. Strain LCS9T grew at 10-37 degrees C (optimum, 25 degrees C) and at pH 6.0-10.0 (optimum, pH 7); was positive for catalase and oxidase; and negative for nitrate reduction and production of indole. Cells showed pigment absorbance peaks at 451 and 479 nm, and had 0.03 % survival following exposure to 3 kGy gamma radiation. Strain LCS9T had the following chemotaxonomic characteristics: the major quinone was menaquinone-7 (MK-7); the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3 OH; polar lipids included phosphoatidylethanolamine, an unidentified aminophospholipid, unidentified aminolipidsand unidentified lipids. The DNA G+C content was 39.4 mol%. Based on polyphasic analysis, the type strain LCS9T (=KCTC 42070T=JCM 19972T) represents a novel species for which the name Flavisolibacter tropicus sp. nov. is proposed. Radiation resistance in the genus Flavisolibacter has not been reported to date, and so this is the first report of low-level radiation resistance of a member of the genus. PMID- 27259555 TI - The subtilisin-like protease SBT3 contributes to insect resistance in tomato. AB - Subtilisin-like proteases (SBTs) constitute a large family of extracellular plant proteases, the function of which is still largely unknown. In tomato plants, the expression of SBT3 was found to be induced in response to wounding and insect attack in injured leaves but not in healthy systemic tissues. The time course of SBT3 induction resembled that of proteinase inhibitor II and other late wound response genes suggesting a role for SBT3 in herbivore defense. Consistent with such a role, larvae of the specialist herbivore Manduca sexta performed better on transgenic plants silenced for SBT3 expression (SBT3-SI). Supporting a contribution of SBT3 to systemic wound signaling, systemic induction of late wound response genes was attenuated in SBT3-SI plants. The partial loss of insect resistance may thus be explained by a reduction in systemic defense gene expression. Alternatively, SBT3 may play a post-ingestive role in plant defense. Similar to other anti-nutritive proteins, SBT3 was found to be stable and active in the insect's digestive system, where it may act on unidentified proteins of insect or plant origin. Finally, a reduction in the level of pectin methylesterification that was observed in transgenic plants with altered levels of SBT3 expression suggested an involvement of SBT3 in the regulation of pectin methylesterases (PMEs). While such a role has been described in other systems, PME activity and the degree of pectin methylesterification did not correlate with the level of insect resistance in SBT3-SI and SBT3 overexpressing plants and are thus unrelated to the observed resistance phenotype. PMID- 27259557 TI - Distal femur reconstruction with modular tumour prostheses: a single Institution analysis of implant survival comparing fixed versus rotating hinge knee prostheses. AB - PURPOSE: To evaluate the incidence of complications in distal femur reconstructions with modular prostheses, comparing fixed vs rotating hinge knee. METHODS: Retrospective analysis of implant survival, complications, and functional results of the Rizzoli series on distal femur megaprosthesis. Between 1983 and 2010, 687 distal femur tumour modular prostheses were implanted: 491 fixed hinge and 196 rotating hinge knee prostheses. Failures of the prostheses were classified in five types: type 1, soft tissue failure; type 2, aseptic loosening; type 3, structural failure; type 4, infection; type 5, tumour progression. RESULTS: Failure rate was 27 % (185/687). Implant survival to all types of failure was 70 % at ten years and 50 % at 20 years with no significant difference between fixed and rotating hinge knee prostheses (p = 0.0928). When excluding type 5 and type 1 failures, the overall survival was 78 % and 58 % at ten and 20 years. There was not a significant difference in implant survival to aseptic loosening (p = 0.5) and infection (p = 0.2) between fixed and rotating hinge knee prostheses. All cases of breakage of prosthetic components occurred in fixed hinge knee prostheses. Functional results, evaluated in 536 pts, were satisfactory in 91.4 % of cases with a mean score of 23.3 with a significantly better function for rotating hinge knee prostheses (p < 0.001). CONCLUSIONS: The most frequent cause of failure was infection followed by aseptic loosening. Even if better results were expected for rotating hinge knee prostheses, there is no significant difference in overall implant survival. No cases of breakage of prosthetic components occurred in rotating hinge knee prosthesis. Functional results were significantly better for the rotating hinge knee prostheses. LEVEL OF EVIDENCE: Therapeutic study, level IV (case series). PMID- 27259558 TI - Immunotherapy of Melanoma. AB - Arising from melanocytes in skin, mucosal membranes, eye, and meninges, melanoma is a tumor that has been associated with poor prognosis in advanced disease stages. Given the poor response to chemotherapy and radiation therapy, new treatment approaches with targeted therapy, immunotherapy, and adoptive T-cell therapy have revolutionized the standard of care for patients with advanced melanoma. This review provides a short overview of past, present, and future immunotherapeutic approaches and their limitations, with a focus on new combination agents in early clinical trials. PMID- 27259559 TI - Methods for determining time of death. AB - Medicolegal death time estimation must estimate the time since death reliably. Reliability can only be provided empirically by statistical analysis of errors in field studies. Determining the time since death requires the calculation of measurable data along a time-dependent curve back to the starting point. Various methods are used to estimate the time since death. The current gold standard for death time estimation is a previously established nomogram method based on the two-exponential model of body cooling. Great experimental and practical achievements have been realized using this nomogram method. To reduce the margin of error of the nomogram method, a compound method was developed based on electrical and mechanical excitability of skeletal muscle, pharmacological excitability of the iris, rigor mortis, and postmortem lividity. Further increasing the accuracy of death time estimation involves the development of conditional probability distributions for death time estimation based on the compound method. Although many studies have evaluated chemical methods of death time estimation, such methods play a marginal role in daily forensic practice. However, increased precision of death time estimation has recently been achieved by considering various influencing factors (i.e., preexisting diseases, duration of terminal episode, and ambient temperature). Putrefactive changes may be used for death time estimation in water-immersed bodies. Furthermore, recently developed technologies, such as H magnetic resonance spectroscopy, can be used to quantitatively study decompositional changes. This review addresses the gold standard method of death time estimation in forensic practice and promising technological and scientific developments in the field. PMID- 27259560 TI - Effect of colestimide on the concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dizenzofurans, and polychlorinated biphenyls in blood of Yusho patients. AB - BACKGROUND: Oral colestimide was reported to lower the concentration of PCDDs, PCDFs, and PCB in the blood of humans. A pilot study showed that the arithmetic mean total TEQ concentrations of PCDDs, PCDFs, and PCBs in the blood of subjects after the trial decreased approximately 20 % compared to pre-trial levels, suggesting that colestimide could decrease human dioxin levels. We designed the current clinical trial study based on this information. In this study, we examined whether colestimide could reduce the individual congener concentrations of PCDDs, PCDFs, and PCBs in the blood of Yusho patients. METHODS: Out of the 36 Yusho patients who participated in the clinical trial, 26 patients self administered colestimide 3 g/day orally for 6 months. The concentrations of PCDDs, PCDFs and PCBs in the blood of 26 Yusho patients before the trial were compared with those after the trial. RESULTS: The arithmetic mean total TEQ concentrations of PCDDs, PCDFs, non-ortho PCBs, and mono-ortho PCBs in the blood of the 26 Yusho patients before and after the clinical trial were 42-303 (mean: 130, median: 120) and 43-283 (mean: 132, median: 118) pg TEQ/g lipid, respectively. The sums of the concentrations of 58 PCB congeners measured in the blood of Yusho patients before and after the trial were 321-2643 (mean: 957, median: 872) and 286-2007 (mean: 975, median: 806) ng/g lipid, respectively, indicating that the concentrations of PCDDs, PCDFs, and PCBs after the trial were almost the same as those before the trial. Among congeners of PCDDs, PCDFs, dioxin-like PCBs, and non-dioxin-like PCBs, most congeners of these compounds did not show a statistically significant decrease after the trial. CONCLUSION: Colestimide may not be beneficial in reducing the high blood levels of dioxin like compounds in Yusho patients. PMID- 27259561 TI - Ex Vivo Testing of Patient-Derived Xenografts Mirrors the Clinical Outcome of Patients with Pancreatic Ductal Adenocarcinoma. AB - PURPOSE: Translation of the patient-derived xenograft (PDX) model into a method for practical personalized cancer treatment is prevented by the intense resources and time necessary to generate and test each tumorgraft. We aimed to develop a high-throughput ex vivo drug testing approach that can be used for personalized cancer treatment design. EXPERIMENTAL DESIGN: We developed a unique ex vivo live tissue sensitivity assay (LTSA), in which precision-cut and uniform small tissue slices derived from pancreatic ductal adenocarcinoma PDX tumors were arrayed in a 96-well plate and screened against clinically relevant regimens within 3 to 5 days. The correlation between the sensitivities of tissue slices to the regimens and patients' clinical responses and outcome were statistically analyzed. The results of LTSA assay were further confirmed with biochemical methods in vitro and animal PDX model in vivo RESULTS: The ex vivo tissue slices remain viable for at least 5 days, and the tumor parenchyma, including stroma, vascular structures, and signaling pathways, are all retained. The sensitivities of the ex vivo tissue slices to gemcitabine and irinotecan was consistent with the clinical responses and outcomes of the patients from whom the tumorgrafts were derived (r = 0.77; P = 0.0002). Retrospective analysis showed that the patients who received LTSA sensitive regimens had remarkably longer progression-free survival than patients who received LTSA-resistant regimens (16.33 vs. 3.8 months; n = 18, P = 0.011). CONCLUSIONS: The results from these PDX and LTSA methods reflect clinical patients' responses and could be used as a personalized strategy for improving systemic therapy effectiveness in patients with pancreatic cancer. Clin Cancer Res; 22(24); 6021-30. (c)2016 AACR. PMID- 27259562 TI - Radiotherapy for Non-Small Cell Lung Cancer Induces DNA Damage Response in Both Irradiated and Out-of-field Normal Tissues. AB - PURPOSE: To study the response of irradiated and out-of-field normal tissues during localized curative intent radiotherapy. EXPERIMENTAL DESIGN: Sixteen patients with non-small cell lung carcinoma (NSCLC) received 60 Gy in 30 fractions of definitive thoracic radiotherapy with or without concurrent chemotherapy. Peripheral blood lymphocytes (PBL) and eyebrow hairs were sampled prior, during, and after radiotherapy. Clinical variables of radiotherapy dose/volume, patient age, and use of chemoradiotherapy were tested for association with gamma-H2AX foci, a biomarker of DNA damage that underlies cellular response to irradiation. RESULTS: Radiotherapy induced an elevation of gamma-H2AX foci in PBL, representing normal tissues in the irradiated volume, 1 hour after fraction one. The changes correlated directly with mean lung dose and inversely with age. gamma-H2AX foci numbers returned to near baseline values in 24 hours and were not significantly different from controls at 4 weeks during radiotherapy or 12 weeks after treatment completion. In contrast, unirradiated hair follicles, a surrogate model for out-of-field normal tissues, exhibited delayed "abscopal" DNA damage response. gamma-H2AX foci significantly increased at 24 hours post-fraction one and remained elevated during treatment, in a dose independent manner. This observed abscopal effect was associated with changes in plasma levels of MDC/CCL22 and MIP-1alpha/CCL3 cytokines. No concordant changes in size and concentration of circulating plasma exosomes were observed. CONCLUSIONS: Both localized thoracic radiotherapy and chemoradiotherapy induce pronounced systemic DNA damage in normal tissues. Individual assessment of biologic response to dose delivered during radiotherapy may allow for therapeutic personalization for patients with NSCLC. Clin Cancer Res; 22(19); 4817-26. (c)2016 AACRSee related commentary by Verma and Lin, p. 4763. PMID- 27259563 TI - Programmed cell death-1 blockade in recurrent disseminated Ewing sarcoma. AB - BACKGROUND: Ewing sarcoma (EWS) is a malignant tumour of bone and soft tissue, and although many patients are cured with conventional multimodal therapy, those with recurrent or metastatic disease have a poor prognosis. Genomic instability and programmed cell death ligand-1 (PD-L1) expression have been identified in EWS, providing a rationale for treatment with agents that block the programmed cell death-1 (PD-1) receptor. CASE PRESENTATION: In this report, we describe a heavily pre-treated patient with recurrent metastatic EWS who achieved a clinical and radiological remission with PD-1 blockade. CONCLUSIONS: To our knowledge, this is the first reported case demonstrating efficacy of PD-1 blockade in EWS. This warrants further investigation in particular given the poor prognosis in patients with recurrent or metastatic disease. PMID- 27259565 TI - Long-Term Exposure to American and European Movies and Television Series Facilitates Caucasian Face Perception in Young Chinese Watchers. AB - Most young Chinese people now learn about Caucasian individuals via media, especially American and European movies and television series (AEMT). The current study aimed to explore whether long-term exposure to AEMT facilitates Caucasian face perception in young Chinese watchers. Before the experiment, we created Chinese, Caucasian, and generic average faces (generic average face was created from both Chinese and Caucasian faces) and tested participants' ability to identify them. In the experiment, we asked AEMT watchers and Chinese movie and television series (CMT) watchers to complete a facial norm detection task. This task was developed recently to detect norms used in facial perception. The results indicated that AEMT watchers coded Caucasian faces relative to a Caucasian face norm better than they did to a generic face norm, whereas no such difference was found among CMT watchers. All watchers coded Chinese faces by referencing a Chinese norm better than they did relative to a generic norm. The results suggested that long-term exposure to AEMT has the same effect as daily other-race face contact in shaping facial perception. PMID- 27259564 TI - Cerebellar Mild Iron Accumulation in a Subset of FMR1 Premutation Carriers with FXTAS. AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene. Iron is essential for many facets of cell metabolism in the brain but when altered is likely to contribute to the development of neurodegenerative diseases. We previously reported that iron accumulates in the choroid plexus and the putamen in FXTAS and that the level and distribution of key iron-binding proteins are also altered, suggesting a potential alteration of iron metabolism in the brain. Here, we hypothesize that iron metabolism is also altered in the FXTAS cerebellum. To test this hypothesis, we used cerebellum samples collected from FXTAS and control subjects and measured the amount of iron contained within the cerebellar cortex and dentate nucleus. We found that the number of iron deposits increased in the cerebellum only in a subset of cases of FXTAS. This accumulation is likely to be mediated by factors other than or in addition to CGG-repeat coupled pathology. Thus, iron deposition in the cerebellum cannot be used as a hallmark of FXTAS pathogenesis. PMID- 27259566 TI - Perceptual Experience of Visual Motion Activates hMT+ Independently From the Physical Reality: fMRI Insights From the Looming Pinna Figure. AB - The human motion processing area, hMT+, has been labeled the critical neural area for processing of real and illusory visual motion in radial 2D patterns. However, the activation in hMT+ during perception of illusory rotation in the looming double-circular Pinna Figure (PF) generated in 3D space has not been observed yet. To do so, an optic-flow like motion of rings (looming) in PF was generated on a computer screen. A psychophysically precise nulling procedure allowed quantifying the individual amount of the perceived illusory rotation in PF (PI) for each participant. The interpolation of the individual illusory motion parameters created a subjectively non-rotating PF and a physically rotating control stimulus of identical rotary strength as the PI. The physically rotating control was a double-circular figure which diverged from PF only in its arrangement of luminance gradients. In a 3-Tesla scanner, participants were presented with a random order of rotating and non-rotating figures (illusory, real, no rotation, and nulled PI). Both types, illusory and real rotation, when equal in perceptual strength for the observer, were found to be processed by hMT+. PMID- 27259567 TI - Influence of hospital type on survival in stage IV colorectal cancer. AB - PURPOSE: Hospital factors along with various patient and surgeon factors are considered to affect the prognosis of colorectal cancer. Hospital volume is well known, but little is known regarding other hospital factors. METHODS: We reviewed data on 853 patients with stage IV colorectal cancer who underwent elective palliative primary tumor resection between January 2006 and December 2007. To detect the hospital factors that could influence the prognosis of incurable colorectal cancer, the relationships between patient/hospital factors and overall survival were analyzed. Among hospital factors, hospital type (Group A: university hospital or cancer center; Group B: community hospital), hospital volume, and number of colorectal surgeons were examined. RESULTS: In univariate analysis, Group A hospitals showed significantly better prognosis than Group B hospitals (p = 0.034), while hospital volume and number of colorectal surgeons were not associated with overall survival. After adjustment for patient factors in multivariate analysis, hospital type was significantly associated with overall survival (hazard ratio: 1.31; 95 % confidence interval: 1.05-1.63; p = 0.016). However, there was no significant difference in short-term outcomes between hospital types. CONCLUSIONS: Hospital type was identified as a hospital factor that possibly affects the prognosis of stage IV colorectal cancer patients. PMID- 27259568 TI - Impact of the introduction of a standardised ICD programming protocol: real-world data from a single centre. AB - PURPOSE: Randomised trials have shown that empiric ICD programming, using long detection times and high detection zones, reduces device therapy in ICD recipients. However, there is less data on its effectiveness in a "real-world" setting, especially secondary prevention patients. Our aim was to evaluate the introduction of a standardised programming protocol in a real-world setting of unselected ICD recipients. METHODS: We analysed 270 consecutive ICD recipients implanted in a single centre-135 implanted prior to protocol implementation (physician-led group) and 135 after (standardised group). The protocol included long arrhythmia detection times (30/40 or equivalent) and high rate detection zones (primary prevention lower treatment zone 200 bpm). Programming in the physician-led group was at the discretion of the implanter. The primary endpoint was time-to-any therapy (ATP or shocks). Secondary endpoints were time-to inappropriate therapy and time-to-appropriate therapy. The safety endpoints were syncopal episodes, hospital admissions and death. RESULTS: At 12 months follow up, 47 patients had received any ICD therapy (physician-led group, n = 31 vs. standardised group, n = 16). There was a 47 % risk reduction in any device therapy (p = 0.04) and an 86 % risk reduction in inappropriate therapy (p = 0.009) in the standardised compared to the physician-led group. There was a non significant 30 % risk reduction in appropriate therapy (p = 0.32). Results were consistent across primary and secondary prevention patients. There were no significant differences in the rates of syncope, hospitalisation, and death. CONCLUSIONS: In unselected patients in a real-world setting, introduction of a standardised programming protocol, using long detection times and high detection zones, significantly reduces the burden of ICD therapy without an increase in adverse outcomes. PMID- 27259570 TI - Normative data for distal line bisection and baking tray task. AB - Line bisection is one of the tests used to diagnose unilateral spatial neglect (USN). Despite its wide application, no procedure or norms were available for the distal variant when the task was performed at distance with a laser pointer. Furthermore, the baking tray task was an ecological test aimed at diagnosing USN in a more natural context. The aim of this study was to collect normative values for these two tests in an Italian population. We recruited a sample of 191 healthy subjects with ages ranging from 20 to 89 years. They performed line bisection with a laser pointer on three different line lengths (1, 1.5, and 2 m) at a distance of 3 m. After this task, the subjects performed the baking tray task and a second repetition of line bisection to test the reliability of measurement. Multiple regression analysis revealed no significant effects of demographic variables on the performance of both tests. Normative cut-off values for the two tests were developed using non-parametric tolerance intervals. The results formed the basis for clinical use of these two tools for assessing lateralized performance of patients with brain injury and for diagnosing USN. PMID- 27259571 TI - Sporadic cerebral amyloid angiopathy as a cause of relapsing lobar hemorrhage, convexal subarachnoid hemorrhage and cortical superficial siderosis. PMID- 27259572 TI - Assessment of outcome after hip fracture: development of a universal assessment system for hip fractures. AB - BACKGROUND: The aim of the study was to refine current evaluation systems used to assess outcome after a hip fracture and to devise a simple and practical system to assess all hip fracture patients. METHODS: Three continuous scales were defined for pain, mobility and functional independence. These were all found to have an acceptable degree of inter-observer agreement. The pre-fracture mobility and independence scores were related to the one-year mortality for a consecutive series of 381 patients. RESULTS: Scores for mobility and functional independence were highly predictive of mortality (p < 0.0001). CONCLUSIONS: It is recommended that the outcome after hip fracture should be standardised to these principle outcomes of pain, regain of mobility and independence and mortality. These scores can be use to assess progress and identify those who may require additional assessment or intervention. PMID- 27259573 TI - Loss, transition and trust: perspectives of terminally ill patients and their oncologists when transferring care from the hospital into the community at the end of life. AB - INTRODUCTION: Most people prefer to die at home. However, most continue to die in hospital. Little is known about the impact on the patient of transferring care from acute sector specialist follow-up to the community. In one cancer centre, a new service-Hospital2Home was set up to facilitate this transfer of care. This study aimed to explore patients' and oncologists' perspectives of the meanings involved in this transition. METHODS: Qualitative study using semistructured one to-one interviews with 8 terminally ill cancer patients and 13 oncologists. The interviews were audio recorded, transcribed verbatim and analysed using the framework approach. RESULTS: 3 main themes were identified: loss, transition and community care. The theme of loss referred to losses associated with the end of treatment and losses associated with the familiar safe relationship between the patient and oncologist. Transition refers to the change from hospital-led to community-based care. Barriers to transition included patient and family acceptance, attachment and concerns about community services. Transition was more acceptable if initiated in a gradual manner. Community care: participants found the Hospital2Home service crucial in establishing new trustworthy relationships between community providers and the patient. CONCLUSIONS: Transfer of care from the acute sector to the community represents a delicate crossroad where complex notions of loss should not be underestimated. A gradual transfer of care may improve this if the patient's condition allows. Therefore, introductions to the community team should be timely, and a staggered transfer should be planned. This would improve the experience of the patient, carer and oncologist. PMID- 27259574 TI - Psychometric evaluation of the Persian version of the Templer's Death Anxiety Scale in cancer patients. AB - In this study, 398 Iranian cancer patients completed the 15-item Templer's Death Anxiety Scale (TDAS). Tests of internal consistency, principal components analysis, and confirmatory factor analysis were conducted to assess the internal consistency and factorial validity of the Persian TDAS. The construct reliability statistic and average variance extracted were also calculated to measure construct reliability, convergent validity, and discriminant validity. Principal components analysis indicated a 3-component solution, which was generally supported in the confirmatory analysis. However, acceptable cutoffs for construct reliability, convergent validity, and discriminant validity were not fulfilled for the three subscales that were derived from the principal component analysis. This study demonstrated both the advantages and potential limitations of using the TDAS with Persian-speaking cancer patients. PMID- 27259575 TI - The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters (223)Ra, (188)Re, and (99m)Tc. AB - BACKGROUND: DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by (223)Ra compared to (188)Re and (99m)Tc modulated by the radical scavenger dimethyl sulfoxide (DMSO). METHODS: Radioactive solutions of (223)Ra, (188)Re, or (99m)Tc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay. RESULTS: Exposure to 120 Gy of (223)Ra, (188)Re, or (99m)Tc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy (223)Ra and 500 Gy (188)Re or (99m)Tc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the alpha-emitter (223)Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with (223)Ra, (188)Re, and (99m)Tc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 +/- 0.04, 1.20 +/- 0.19, and 1.34 +/- 0.05 for (223)Ra, (188)Re, and (99m)Tc, respectively. CONCLUSIONS: For (223)Ra, as well as for (188)Re and (99m)Tc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the alpha-particle induced DNA damage. PMID- 27259576 TI - Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjogren's syndrome treated with Infliximab: a pilot study. AB - BACKGROUND: Human T lymphocytes infiltrating tissues in autoimmune diseases are known to express somatostatin receptors amongst other activation markers. In this study, we evaluated whether somatostatin receptor scintigraphy (SRS) using a radiolabelled somatostatin analogue ((99m)Tc-EDDA/tricine-HYNIC-tyr(3)-octreotide ((99m)Tc-EDDA/HYNIC-TOC)) is able to detect the presence of immune-mediated processes in patients with rheumatoid arthritis and secondary Sjogren's syndrome. We also aimed to evaluate whether positivity to SRS was predictive of therapeutic response and if SRS could be used for monitoring the efficacy of immunomodulatory treatment. METHODS: Eighteen patients with rheumatoid arthritis and secondary Sjogren's syndrome not responding to conventional treatment were recruited for treatment with infliximab, a monoclonal antibody against TNF-alpha. All patients had complete blood cell count, renal and liver function tests, measurements of ESR, CRP, ANA, ENA, and anti-dsDNA antibodies, functional salivary gland scintigraphy, labial biopsy, and ophthalmologic assessment with Schirmer's test and tear film break-up time (BUT). Diagnosis was made according to the revised criteria of the American-European Consensus Group. All patients underwent SRS at baseline and after 3-6 months of therapy with infliximab. Eleven out of 18 had repeat SRS images. Images of the salivary glands and major joints were acquired 3 h after injection of 370 MBq of (99m)Tc-EDDA/HYNIC-TOC. Image analysis was performed semi-quantitatively. RESULTS: All patients showed uptake of (99m)Tc EDDA/HYNIC-TOC in the joints. Salivary glands also showed variable radiopharmaceutical uptake in 12 out of 18 patients, but all patients showed presence of lymphocytic infiltration at labial salivary gland biopsy. All patients, who repeated the study after treatment, showed significant reduction of somatostatin uptake in the joints but not in the salivary glands. CONCLUSIONS: SRS using (99m)Tc-EDDA/HYNIC-TOC may be a useful imaging tool to assess disease activity and extent in patients with rheumatoid arthritis and may help to detect secondary Sjogren's syndrome. It may also aid therapy decision-making with anti TNFalpha antibodies in the joints but not in salivary glands. PMID- 27259577 TI - A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma. AB - BACKGROUND: Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. METHODS: A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. RESULTS: The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. CONCLUSIONS: Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma. PMID- 27259578 TI - Successful laparoscopic distal gastrectomy with D2 lymph node dissection preserving the common hepatic artery branched from the left gastric artery for advanced gastric cancer with an Adachi type VI (group 26) vascular anomaly. AB - We report a case of successful laparoscopic distal gastrectomy with D2 lymph node dissection preserving the common hepatic artery branched from the left gastric artery for advanced gastric cancer with an Adachi type VI (group 26) vascular anomaly. A 76-year-old female patient was admitted with a diagnosis of advanced gastric cancer at the anterior wall to the lesser curvature of the antrum (cT3N0M0 cStage IIA). Dynamic computed tomography showed the ectopia of the common hepatic artery branched from the left gastric artery. We made a diagnosis of an Adachi type VI (group 26) vascular anomaly and performed the abovementioned operation. In this anomaly pattern, scrupulous attention is required to remove the suprapancreatic lymph nodes because the portal vein is located immediately dorsal to those lymph nodes and is at increased risk for the injury in this situation. The common hepatic artery is branched from the left gastric artery, and the hepatic perfusion from the superior mesenteric artery is not present in group 26. Planning to preserve the artery will improve safety when it is possible oncologically. There were no postoperative complications, and the patient was discharged 9 days after the operation. To our knowledge, the present case is the first reported case of a laparoscopic distal gastrectomy with D2 lymph node dissection with an Adachi type VI (group 26) vascular anomaly. Preoperative diagnostic imaging is very important to prevent surgical complications because the reliable identification of vascular anomaly during an operation is very difficult. PMID- 27259579 TI - Laparoscopy-assisted distal gastrectomy for early gastric cancer poses few limitations for selected elderly patients: a single-center experience. AB - BACKGROUND: The safety and efficacy of laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer have been demonstrated in clinical studies. The aim of this study was to clarify the safety and efficacy of LADG in patients >=80 years of age with early gastric cancer, an American Society of Anesthesiologists (ASA) classification of 1-2, and a performance status (PS) of 0-1. CASE PRESENTATION: From April 2009 to July 2011, 12 elderly patients aged >=80 years and 43 younger patients underwent LADG for early gastric cancer. Seven of the 55 patients underwent LADG and simultaneous surgery including surgery for colorectal cancer, cholecystectomy, or other conditions. Forty-eight of the 55 patients who underwent only LADG were studied. Demographics and postoperative outcomes were compared. RESULTS: The postoperative complication rate, time to first ambulation, time to first flatus, time to first fluid intake, and postoperative hospital stay were similar in these two groups. Nutritional status as assessed by body weight, serum albumin, and total protein at 1 and 3 months after surgery was also similar in these two groups. CONCLUSIONS: Postoperative outcomes were acceptable in the elderly patients included in the study. LADG for early gastric cancer is a safe and effective treatment in elderly patients aged >=80 years with an ASA status of 1-2 and PS of 0-1. PMID- 27259580 TI - Health-related quality of life in patients with psoriasis: a systematic review of the European literature. AB - PURPOSE: To summarize the data published over the last 5 years in the European Union related to the health-related quality of life (HRQoL) of patients with psoriasis and its conditioning factors. METHODS: International electronic databases and gray literature were searched to identify studies conducted on patient-reported outcomes in patients with psoriasis, published in Europe between January 1, 2009 and December 31, 2013. Bibliographic references were hand searched. Editorials, letters, commentaries, opinion papers, and studies related to specific treatments were excluded. RESULTS: A total of 46 studies met the inclusion criteria, 27 of them reporting data related to HRQoL or its conditioning factors. The publications reviewed highlighted the substantial negative impact of psoriasis on patients' HRQoL. Most of the studies that analyzed the relationship between HRQoL and sociodemographic characteristics described a relation between gender (female) and age (young patients) and poorer HRQoL. An association between HRQoL impairment and visibility of skin lesions and disease activity and severity was also established. Skin discomfort and pruritus were identified as elements that negatively influenced HRQoL. Use of biological agents had a positive impact on HRQoL and on treatment satisfaction, a better HRQoL being seen in patients treated with systemic therapies and biologics. CONCLUSIONS: HRQoL has been broadly addressed in patients with psoriasis in Europe. Several disease- and patient-related factors contributed to its deterioration. Therapeutic measures with proven effectiveness in controlling disease symptoms and reducing PASI should be considered in patients with a severe disease who have a poorer HRQoL. PMID- 27259581 TI - Stigma as a key determinant of health-related quality of life in Parkinson's disease. AB - PURPOSE: People with Parkinson's disease (PD) may experience stigma due to their visible features of movement and communication difficulties. This paper aimed to examine the role of experienced stigma in health-related quality of life (QOL), after controlling for personal and clinical characteristics. METHODS: This is a preliminary analysis of a subset of baseline data from the Social Self-Management of Parkinson's Disease Study (SocM-PD), an ongoing 3-year prospective cohort study. Seventy-three people with PD (M age = 65.72, 29 women) participated in this study. Hierarchical multiple regression analyses were used to determine the role of stigma in QOL, after controlling for gender, disease severity, depression, and motor difficulties of daily living. RESULTS: Significant correlations were found between QOL with gender (r = .26), disease severity (r = .38), depression (r = .65), motor difficulties of daily living (r = .71), and stigma (r = .83). After controlling for the significant covariates, stigma made a significant and unique contribution to the explanation of QOL by 13.7 % (p < 0.001). A final hierarchical multiple regression with stigma and the 4 covariates revealed an overall model that explained 77.8 % of the total variance of QOL (F [5, 63] = 48.79, p < 0.001). CONCLUSIONS: Experienced stigma appears to be a key determinant of QOL in people with PD. The results suggest the importance of further understanding stigma in PD to develop possible intervention strategies. Future work is also needed to verify the results with a larger and longitudinal dataset of the SocM-PD. PMID- 27259582 TI - RNF187 is Downregulated Following NF-kappaB Inhibition in Late Erythroblasts. AB - Beta (beta)-thalassaemic erythroblasts grown in vitro have reduced nuclear factor kappa B (NF-kappaB) pathway gene expression. By inhibiting this pathway in erythroblasts from normal individuals, important downstream genes affected by this inhibition can be identified. Bay 11-7082 is a potent inhibitor of the NF kappaB pathway, it acts irreversibly, inhibiting NF-kappaB activation by blocking tumor necrosis factor alpha (TNF-alpha)-induced phosphorylation of the inhibitory IkappaB subunit thereby preventing NF-kappaB activation. In this study, hematopoietic stem cells were isolated from the peripheral blood of 6 healthy individuals and were then cultured for 14 days in conditions which promote erythroid differentiation. Following erythroid lineage enrichment, these cells were stimulated with TNFalpha or inhibited with Bay 11-7082. Subsequent RNA isolation and gene expression analyses were performed using pooled cDNA with custom PCR arrays. Genes of interest were examined individually on non-pooled samples. Our data identified RNF187, a RING finger domain gene as being downregulated in response to NF-kappaB inhibition. PMID- 27259583 TI - A randomized, controlled trial comparing topical steroid application to wet versus dry skin in children with atopic dermatitis (AD). AB - BACKGROUND: Soak and smear (SS), a technique whereby a bath is followed by topical corticosteroid (TCS) application to wet skin, is reported to be a beneficial adjunctive therapy for patients with recalcitrant atopic dermatitis (AD). OBJECTIVE: We evaluated whether SS is of greater benefit than application of TCS to dry skin for the treatment of childhood AD. METHODS: A randomized, investigator-blinded, controlled study was performed in children with AD. Patients were randomized to apply TCS either via SS (n = 22) or to dry skin (n = 23) for 14 days. The primary outcome was an improvement in the Eczema Area and Severity Index score. Secondary outcomes included assessments of disease burden, pruritus, and sleep; morning cortisol levels; and adverse effects. RESULTS: Patients with AD severity who applied TCS via SS or to dry skin improved 84.8% (95% confidence interval 77.5-92.1) and 81.4% (95% confidence interval 70.3-92.4) by Eczema Area and Severity Index score, respectively. There was no statistical difference between the 2 groups (P value = .85). LIMITATIONS: Small sample size limited the power of our study. CONCLUSIONS: We did not find that application of TCS to presoaked skin works better than application to dry skin for the treatment of AD in children. PMID- 27259584 TI - Task modulated brain connectivity of the amygdala: a meta-analysis of psychophysiological interactions. AB - Understanding functional connectivity of the amygdala with other brain regions, especially task modulated connectivity, is a critical step toward understanding the role of the amygdala in emotional processes and the interactions between emotion and cognition. The present study performed coordinate-based meta-analysis on studies of task modulated connectivity of the amygdala which used psychophysiological interaction (PPI) analysis. We first analyzed 49 PPI studies on different types of tasks using activation likelihood estimation (ALE) meta analysis. Widespread cortical and subcortical regions showed consistent task modulated connectivity with the amygdala, including the medial frontal cortex, bilateral insula, anterior cingulate, fusiform gyrus, parahippocampal gyrus, thalamus, and basal ganglia. These regions were in general overlapped with those showed coactivations with the amygdala, suggesting that these regions and amygdala are not only activated together, but also show different levels of interactions during tasks. Further analyses with subsets of PPI studies revealed task specific functional connectivities with the amygdala that were modulated by fear processing, face processing, and emotion regulation. These results suggest a dynamic modulation of connectivity upon task demands, and provide new insights on the functions of the amygdala in different affective and cognitive processes. The meta-analytic approach on PPI studies may offer a framework toward systematical examinations of task modulated connectivity. PMID- 27259585 TI - Human navigation network: the intrinsic functional organization and behavioral relevance. AB - Spatial navigation is a crucial ability for living. Previous work has revealed multiple distributed brain regions associated with human navigation. However, little is known about how these regions work together as a network (referred to as navigation network) to support flexible navigation. In a novel protocol, we combined neuroimaging meta-analysis, and functional connectivity and behavioral data from the same subjects. Briefly, we first constructed the navigation network for each participant, by combining a large-scale neuroimaging meta-analysis (with the Neurosynth) and resting-state functional magnetic resonance imaging. Then, we investigated multiple topological properties of the navigation networks, including small-worldness, modularity, and highly connected hubs. Finally, we explored the behavioral relevance of these intrinsic properties in a large sample of healthy young adults (N = 190). We found that navigation networks showed small world and modular organization at global level. More importantly, we found that increased small-worldness and modularity of the navigation network were associated with better navigation ability. Finally, we found that the right retrosplenial complex (RSC) acted as one of the hubs in the navigation network, and that higher betweenness of this region correlated with better navigation ability, suggesting a critical role of the RSC in modulating the navigation network in human brain. Our study takes one of the first steps toward understanding the underlying organization of the navigation network. Moreover, these findings suggest the potential applications of the novel approach to investigating functionally meaningful networks in human brain and their relations to the behavioral impairments in the aging and psychiatric patients. PMID- 27259586 TI - Evaluation of WGA-Cre-dependent topological transgene expression in the rodent brain. AB - Novel neuromodulation techniques in the field of brain research, such as optogenetics, prompt to target specific cell populations. However, not every subpopulation can be distinguished based on brain area or activity of specific promoters, but rather on topology and connectivity. A fascinating tool to detect neuronal circuitry is based on the transsynaptic tracer, wheat germ agglutinin (WGA). When expressed in neurons, it is transported throughout the neuron, secreted, and taken up by synaptically connected neurons. Expression of a WGA and Cre recombinase fusion protein using a viral vector technology in Cre-dependent transgenic animals allows to trace neuronal network connections and to induce topological transgene expression. In this study, we applied and evaluated this technology in specific areas throughout the whole rodent brain, including the hippocampus, striatum, substantia nigra, and the motor cortex. Adeno-associated viral vectors (rAAV) encoding the WGA-Cre fusion protein under control of a CMV promoter were stereotactically injected in Rosa26-STOP-EYFP transgenic mice. After 6 weeks, both the number of transneuronally labeled YFP+/mCherry- cells and the transduced YFP+/mCherry+ cells were quantified in the connected regions. We were able to trace several connections using WGA-Cre transneuronal labeling; however, the labeling efficacy was region-dependent. The observed transneuronal labeling mostly occurred in the anterograde direction without the occurrence of multi-synaptic labeling. Furthermore, we were able to visualize a specific subset of newborn neurons derived from the subventricular zone based on their connectivity. PMID- 27259587 TI - Yeast ABC transporters in lipid trafficking. AB - Throughout its evolution, the ATP-binding cassette (ABC) transporter superfamily has experienced a rapid expansion in its substrate repertoire and functions. Of the diverse functions that these pumps offer, their drug transport properties have attracted considerable attention primarily owing to their clinical significance. Despite this fact, emerging evidence suggests that physiological substrates of transporters also affect the overall functioning of an organism. Lipids, as substrates of ABC transporters, constitute one feature found in all representative groups of the living kingdom. Due to the importance of lipid species in the cellular physiology of an organism, their proper distribution within cells is crucial. This fact is well exemplified by the vast number of medical conditions that have been caused as a result of perturbations in ABC transporter-mediated lipid transport in higher organisms. In yeasts, apart from providing transport functions, ABC transporters also coordinate regulatory networks with lipids. This review focuses on yeast ABC transporters involved in the transport of lipids and briefly discusses the integration of their regulatory network with that of the lipid species. PMID- 27259589 TI - Central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio: An experimental model or a bedside clinical tool? PMID- 27259588 TI - Rates of workplace aggression in the emergency department and nurses' perceptions of this challenging behaviour: A multimethod study. AB - INTRODUCTION: Over the last 10 years, the rate of people presenting with challenging behaviour to emergency departments (EDs) has increased and is recognised as a frequent occurrence facing clinicians today. Challenging behaviour often includes verbal aggression, physical aggression, intimidation and destruction of property. AIM: The aim of this research was to (i) identify the characteristics and patterns of ED-reported incidents of challenging behaviour and (ii) explore emergency nurses' perceptions of caring for patients displaying challenging behaviour. METHODS: This was a multi-method study conducted across two metropolitan Sydney district hospitals. Phase 1 involved a 12-month review of the hospital's incident management database. Phase 2 involved a survey of emergency nurses' perceptions of caring for patients displaying challenging behaviour. RESULTS: Over 12 months there were 34 incidents of aggression documented and the perpetrators were often male (n=18; 53.0%). The average age was 34.5 years. The majority of reported incidents (n=33; 90.1%) involved intimidation, verbal assault and threatening behaviour. The median time between patient arrival and incident was 109.5min (IQR 192min). The median length of stay for patients was 302.5min (IQR 479min). There was no statistical difference between day of arrival and time of actual incident (t-test p=0.235), length of stay (t-test p=0.963) or ED arrival to incident time (t-test p=0.337). The survey (n=53; 66.2%) identified the average ED experience was 12.2 years (SD 9.8 years). All participants surveyed had experienced verbal abuse and/or physical abuse. Participants (n=52) ranked being spat at (n=37; 71.1%) the most difficult to manage. Qualitative survey open-ended comments were analysed and organised thematically. THEMATIC ANALYSIS: The survey identified three themes which were (i) increasing security, (ii) open access and (iii) rostering imbalance. CONCLUSION: The study provides insight into emergency nurses' reported perceptions of patients who display challenging behaviour. All emergency nurse participants reported being regularly exposed to challenging behaviour and this involved both physical and verbal abuse. This was in contrast to a low incident hospital reporting rate. ED clinicians need to be better supported with targeted educational programmes, appropriate ED architecture and reporting mechanism that are not onerous. PMID- 27259590 TI - Fluorescent In Situ Hybridization Monitoring and Effect of Detected Early Responses in the Outcome of Patients With Chronic Phase Chronic Myeloid Leukemia: A Report From a Latin American Country. AB - INTRODUCTION: The cytogenetic hallmark of chronic myeloid leukemia (CML) is the Philadelphia chromosome. Monitoring the response in patients receiving therapy is a standard of care. The present study was conducted to assess the monitoring adherence and reliableness of fluorescent in situ hybridization (FISH) as a monitoring tool and the effect of a complete cytogenetic response (CCyR) assessed by FISH on the prognosis of patients in a chronic phase (CP)-CML cohort. MATERIALS AND METHODS: We retrospectively analyzed the data from 63 newly diagnosed CP-CML patients treated with imatinib mesylate at a dose of 400 mg/day as frontline therapy. The clinical data and cytogenetic test results at diagnosis and during monitoring were collected. The cytogenetic monitoring adherence assessment rates were measured. A correlation between chromosome banding analysis (CBA) and FISH was performed. The CCyR assessed by FISH was defined as < 1% BCR ABL1(+) nuclei. The Kaplan-Meier method was used for overall survival analysis and time-to-event estimates. RESULTS: The cytogenetic monitoring assessment adherence was 50.8% at 3 months, 93.5% at 6 months, 96.7% at 12 months, and 88.6% at 18 months. The Pearson correlation coefficient showed a significantly positive association (r = 0.84; P < .001) between CBA and FISH. The median follow-up duration after imatinib mesylate initiation was 60 months. A CCyR was achieved in 90.4% of patients within the first 18 months of therapy. At 3 months, 31 patients underwent a FISH evaluation, and 13 (41.9%) had achieved a CCyR. The patients who did not achieve a CCyR at 3 months had a significantly inferior probability of 5 year failure-free survival (38% vs. 94%; P = .001) and progression-free survival (80% vs. 100%; P = .043) compared with those with a CCyR. CONCLUSION: We found improved monitoring adherence compared with the previous reports of Latin American populations. In countries with a high incidence of failure for CBA and a lack of real-time polymerase chain reaction standardization, FISH is a sensitive monitoring tool. In our cohort, patients not achieving an early CCyR, as tested by FISH, were a poor prognosis subgroup with worse rates of failure-free survival and progression-free survival. PMID- 27259635 TI - Responses of hydraulics at the whole-plant level to simulated nitrogen deposition of different levels in Fraxinus mandshurica. AB - Nitrogen (N) deposition is expected to have great impact on forest ecosystems by affecting many aspects of plant-environmental interactions, one of which involves its influences on plant water relations through modifications of plant hydraulic architecture. However, there is a surprising lack of integrative study on tree hydraulic architecture responses to N deposition, especially at the whole-plant level. In the present study, we used a 5-year N addition experiment to simulate the effects of six different levels of N deposition (20-120 kg ha(-1) year(-1)) on growth and whole-plant hydraulic conductance of a dominant tree species (Fraxinus mandshurica Rupr.) from the typical temperate forest of NE China. The results showed that alleviation of N limitation by moderate concentrations of fertilization (20-80 kg ha(-1) year(-1)) promoted plant growth, but further N additions on top of the threshold level showed negative effects on plant growth. Growth responses of F. mandshurica seedlings to N addition of different concentrations were accompanied by corresponding changes in whole-plant hydraulic conductance; higher growth rate was accompanied by reduced whole-plant hydraulic conductance (Kplant) and higher leaf water-use efficiency. A detailed analysis on hydraulic conductance of different components of the whole-plant water transport pathway revealed that changes in root and leaf hydraulic conductance, rather than that of the stem, were responsible for Kplant responses to N fertilization. Both plant growth and hydraulic architecture responses to increasing levels of N addition were not linear, i.e., the correlation between measured parameters and N availability exhibited bell-shaped curves with peak values observed at medium levels of N fertilization. Changes in hydraulic architecture in response to fertilization found in the present study may represent an important underlying mechanism for the commonly observed changes in water-related tree performances in response to N deposition. PMID- 27259591 TI - Breast cancer subtype predictors revisited: from consensus to concordance? AB - BACKGROUND: At the molecular level breast cancer comprises a heterogeneous set of subtypes associated with clear differences in gene expression and clinical outcomes. Single sample predictors (SSPs) are built via a two-stage approach consisting of clustering and subtype predictor construction based on the cluster labels of individual cases. SSPs have been criticized because their subtype assignments for the same samples were only moderately concordant (Cohen's kappa<0.6). METHODS: We propose a semi-supervised approach where for five datasets, consensus sets were constructed consisting of those samples that were concordantly subtyped by a number of different predictors. Next, nine subtype predictors - three SSPs, three subtype classification models (SCMs) and three novel rule-based predictors based on the St. Gallen surrogate intrinsic subtype definitions (STGs) - were constructed on the five consensus sets and their associated consensus subtype labels. The predictors were validated on a compendium of over 4,000 uniformly preprocessed Affymetrix microarrays. Concordance between subtype predictors was assessed using Cohen's kappa statistic. RESULTS: In this standardized setup, subtype predictors of the same type (either SCM, SSP, or STG) but with a different gene list and/or consensus training set were associated with almost perfect levels of agreement (median kappa>0.8). Interestingly, for a given predictor type a change in consensus set led to higher concordance than a change to another gene list. The more challenging scenario where the predictor type, gene list and training set were all different resulted in predictors with only substantial levels of concordance (median kappa=0.74) on independent validation data. CONCLUSIONS: Our results demonstrate that for a given subtype predictor type stringent standardization of the preprocessing stage, combined with carefully devised consensus training sets, leads to predictors that show almost perfect levels of concordance. However, predictors of a different type are only substantially concordant, despite reaching almost perfect levels of concordance on training data. PMID- 27259636 TI - Overexpression of PtrMYB119, a R2R3-MYB transcription factor from Populus trichocarpa, promotes anthocyanin production in hybrid poplar. AB - Anthocyanins are a group of colorful and bioactive natural pigments with important physiological and ecological functions in plants. We found an MYB transcription factor (PtrMYB119) from Populus trichocarpa that positively regulates anthocyanin production when expressed under the control of the CaMV 35S promoter in transgenic Arabidopsis Amino acid sequence analysis revealed that PtrMYB119 is highly homologous to Arabidopsis PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT1), a well-known transcriptional activator of anthocyanin biosynthesis. Independently produced transgenic poplars overexpressing PtrMYB119 or PtrMYB120 (a paralogous gene to PtrMYB119) (i.e., 35S::PtrMYB119 and 35S::PtrMYB120, respectively) showed elevated accumulation of anthocyanins in the whole plants, including leaf, stem and even root tissues. Using a reverse-phase high performance liquid chromatography, we confirmed that the majority of the accumulated anthocyanin in our transgenic poplar is cyanidin-3-O-glucoside. Gene expression analyses revealed that most of the genes involved in the anthocyanin biosynthetic pathway were highly upregulated in 35S::PtrMYB119 poplars compared with the nontransformed control poplar. Among these genes, expression of PtrCHS1 (Chalcone Synthase1) and PtrANS2 (Anthocyanin Synthase2), which catalyze the initial and last steps of anthocyanin biosynthesis, respectively, was upregulated by up to 350-fold. Subsequent transient activation assays confirmed that PtrMYB119 activated the transcription of both PtrCHS1 and PtrANS2 Interestingly, expression of MYB182, a repressor of both anthocyanin and proanthocyanidin (PA) biosynthesis, was largely suppressed in 35S::PtrMYB119 poplars, while expression of MYB134, an activator of PA biosynthesis, was not changed significantly. More interestingly, high-level accumulation of anthocyanins in 35S::PtrMYB119 poplars did not have an adverse effect on plant growth. Taken together, our results demonstrate that PtrMYB119 and PtrMYB120 function as transcriptional activators of anthocyanin accumulation in both Arabidopsis and poplar. PMID- 27259637 TI - Impacts of prescribed fire on Pinus rigida Mill. in upland forests of the Atlantic Coastal Plain. AB - A comparative analysis of the impacts of prescribed fire on three upland forest stands in the Northeastern Atlantic Plain, NJ, USA, was conducted. Effects of prescribed fire on water use and gas exchange of overstory pines were estimated via sap-flux rates and photosynthetic measurements on Pinus rigida Mill. Each study site had two sap-flux plots, one experiencing prescribed fire and one control (unburned) plot for comparison before and after the fire. We found that photosynthetic capacity in terms of Rubisco-limited carboxylation rate and intrinsic water-use efficiency was unaffected, while light compensation point and dark respiration rate were significantly lower in the burned vs control plots post-fire. Furthermore, quantum yield in pines in the pine-dominated stands was less affected than pines in the mixed oak/pine stand, as there was an increase in quantum yield in the oak/pine stand post-fire compared with the control (unburned) plot. We attribute this to an effect of forest type but not fire per se. Average daily sap-flux rates of the pine trees increased compared with control (unburned) plots in pine-dominated stands and decreased in the oak/pine stand compared with control (unburned) plots, potentially due to differences in fuel consumption and pre-fire sap-flux rates. Finally, when reference canopy stomatal conductance was analyzed, pines in the pine-dominated stands were more sensitive to changes in vapor pressure deficit (VPD), while stomatal responses of pines in the oak/pine stand were less affected by VPD. Therefore, prescribed fire affects physiological functioning and water use of pines, but the effects may be modulated by forest stand type and fuel consumption pattern, which suggests that these factors may need to be taken into account for forest management in fire dominated systems. PMID- 27259638 TI - Physiological aspects of seed recalcitrance: a case study on the tree Aesculus hippocastanum. AB - Recalcitrant seeds are typical of some tropical and subtropical trees. Their post shedding life activity proceeds in humid air and wet litter. They are desiccation sensitive and, for this reason, have a short life span and need some special procedures for cryopreservation. This review is devoted to the post-shedding life strategy of recalcitrant seeds, which includes the maintenance of high hydration status, metabolic readiness and ability to rapidly germinate before desiccation induced damage exerts a lethal effect. The main physiological aspects of recalcitrant seeds are considered starting from mature seeds, followed during dormancy if occurs and resulting in germination. The collected data embrace the metabolic processes in embryonic axes and whole seeds. The up-to-date results are integrated covering the main metabolic processes, namely water status and transport, protein and carbohydrate metabolism, antioxidant defense, axis cotyledon relations, hormonal control and germination. Among the representatives of various taxa, the seeds of which exhibit recalcitrance, attention was given to horse chestnut seeds as one of most studied recalcitrants. PMID- 27259639 TI - [Preclinical models to establish innovative therapy strategies : Ex-vivo assessment of head and neck tumor chemo- and immune responses]. AB - The pharmacological treatment of head and neck squamous cell carcinoma (HNSCC) is currently experiencing an expansion of the spectrum of targeting therapies. It can be expected that use of immune modulators, e.g., checkpoint-inhibitors, and their combination with chemotherapy will lead to a plethora of therapeutic options in the near future, from which the best one for the individual patient can be selected. HNSCCs are heterogeneous in their biology, and responses to chemotherapy are nonuniform and often only observable in subgroups. It would be valuable to know the chance of success of a particular treatment in advance. Evidence-based selection of the best individual treatment is difficult, since predictive biomarkers which are assessable prior to the treatment decision and reliably indicate the suitability of particular therapeutics are lacking. Pretherapeutic predictive ex-vivo chemoresponse testing of HNSCC biopsy specimens could enable identification of responders and allow a more suitable therapy regimen to be chosen for potential non-responders, without exposing them to likely ineffective therapy attempts. However, early ex-vivo assays failed regarding reliable prediction of therapeutic success, even with tolerable doses of pharmaceuticals and, in particular, their combinations. Predictive testing was hence deemed improper for the clinic. Improved methodology has now led to a reappraisal of predictive testing and its additional use in analysis of antitumor immune responses ex vivo. Here we describe recent advances and new results from ex-vivo chemoresponse testing of HNSCC and highlight their ability to facilitate establishment of innovative therapy strategies. PMID- 27259640 TI - [The Freiburg speech intelligibility test : A pillar of speech audiometry in German-speaking countries]. AB - The Freiburg speech intelligibility test according to DIN 45621 was introduced around 60 years ago. For decades, and still today, the Freiburg test has been a standard whose relevance extends far beyond pure audiometry. It is used primarily to determine the speech perception threshold (based on two-digit numbers) and the ability to discriminate speech at suprathreshold presentation levels (based on monosyllabic nouns). Moreover, it is a measure of the degree of disability, the requirement for and success of technical hearing aids (auxiliaries directives), and the compensation for disability and handicap (Konigstein recommendation). In differential audiological diagnostics, the Freiburg test contributes to the distinction between low- and high-frequency hearing loss, as well as to identification of conductive, sensory, neural, and central disorders. Currently, the phonemic and perceptual balance of the monosyllabic test lists is subject to critical discussions. Obvious deficiencies exist for testing speech recognition in noise. In this respect, alternatives such as sentence or rhyme tests in closed answer inventories are discussed. PMID- 27259641 TI - Clinical characteristics of congenital cervical atresia and associated endometriosis among 96 patients. AB - OBJECTIVE: To describe the anatomic variety of congenital cervical atresia and to explore the relationship between this disorder and pelvic endometriosis. METHODS: In a retrospective study, records were reviewed for 96 patients with a confirmed diagnosis of congenital cervical atresia treated at a center in Beijing, China, between January 1984 and October 2014. Data on demographic parameters, symptoms, anatomic features, and endometriosis were obtained and analyzed. RESULTS: Of the 96 patients, 54 (56%) had pelvic endometriosis, 23 (24%) had a uterine malformation, 75 (78%) had a vaginal malformation, and 12 (13%) had a urinary malformation. The patients with a delay from first symptoms to surgery of more than 1year had a higher incidence of endometriosis than did those with a delay of 1year or less (45/71 [63%] vs 7/23 [30%]; P=0.006), and this trend was not related to the severity of endometriosis (P=0.658). Among the 31 patients with unilateral endometrial cysts, 20 (65%) had left-sided cysts and 11 (35%) had right-sided cysts (P=0.005). CONCLUSION: More than half of patients with congenital cervical atresia had pelvic endometriosis. Early diagnosis and surgery seem to be necessary to prevent endometriosis among patients with congenital cervical atresia. PMID- 27259642 TI - Amyloidogenic behavior of different intermediate state of stem bromelain: A biophysical insight. AB - Stem bromelain, a cysteine proteases from Ananas comosus is a widely accepted therapeutic drug with broad medicinal application. It exists as intermediate states at pH 2.0 and 10.0, where it encountered in gastrointestinal tract during adsorption (acidic pH) and in gut epithelium (alkaline pH), respectively. In this study, we monitored the thermal aggregation/amyloid formation of SB at different pH intermediate states. Thermal treatment of stem bromelain at pH 10.0 favors the fibrillation in which the extent of aggregation increases with increase in protein concentration. However, no fibril formation in stem bromelain at pH 2.0 was found at all the concentration used at pH 10.0. The fibril formation was confirmed by various techniques such as turbidity measurements, Rayleigh light scattering, dye binding assays and far UV circular dichroism. The Dynamic light scattering confirmed the formation of aggregates by measuring the hydrodynamic radii pattern. Moreover, microscopic techniques were performed to analyze the morphology of fibrils. The aggregation behavior may be due to variation in number of charged amino acid residues. The less negative charge developed at pH 10.0 may be responsible for aggregation. This work helps to overcome the aggregation related problems of stem bromelain during formulations in pharmaceutical industry. PMID- 27259643 TI - Evaluation of combined B cell specific N-terminal immunogenic domains of LipL21 for diagnosis of leptospirosis. AB - Leptospiral outer membrane protein LipL21 and its truncated N-terminal immunogenic region (I-LipL21) were evaluated for diagnosis of leptospirosis. The complete coding sequence of LipL21 nucleotide sequence was subjected to BCPred and VaxiJen analysis for determination of B cell specific immunogenic epitopes. Epitope1 ACS STD TGQ KDA TTV GDG (1.8837), Epitope2 WGG PPE QRN DGK TPR DTN (0.9483), Epitope3 VKG VGV YEC KAT GSG SDP (1.4077) and Epitope4 NEW ECQ CVI YAK FPG GKD (0.4462) were predicted. LipL21 and N-terminal fragment having B-cell specific epitopes with higher VaxiJen score >0.9 as truncated I-LipL21 were cloned independently in pET15b and expressed in Escherichia coli. IgM ELISA and dot blot assay was performed for sera samples collected from Delhi-NCR for leptospiral whole cell lysate (WCL), recombinant LipL21 and I-LipL21. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were found to be 92.5%, 92.8%, 83.3%, and 97% respectively for recombinant I-LipL21 by IgM-ELISA. 11-14.8% increased sensitivity was observed over LipL21 and WCL. The I-LipL21 dot blot assay showed a further increased sensitivity of 3.8% over the IgM-ELISA. Therefore I-LipL21 may be the ideal candidate protein for diagnosis of leptospirosis. PMID- 27259644 TI - Thermo- and salt-tolerant chitosan cross-linked gamma-glutamyl transpeptidase from Bacillus licheniformis ER15. AB - Gamma-glutamyl transpeptidase enzyme, from Bacillus licheniformis ER15 (BLGGT), was produced extracellularly using a complex medium with high enzyme titers. Enzyme was concentrated and purified using ultra-filtration and ion exchange chromatography, respectively, with a purification fold of 4.6 and 50.11% yield. Enzyme was covalently immobilized onto chitosan microspheres (CMS). Immobilization was standardized with respect to pH, enzyme load and time. Immobilization efficiency of 11.9U/mg dry weight of microsphere was obtained in Tris-HCl buffer (pH 9.0) at 18 degrees C in 4h. Immobilized enzyme (CMS-GGT) exhibited improved thermal stability (t1/2 of 70.7min at 60 degrees C), activity in a broader pH range and improved salt stability in 18% (3M) sodium chloride solution as compared to free enzyme. Both free and immobilized enzymes specifically converted glutamine to glutamic acid in a mixture of amino acids. CMS-GGT had a better shelf life and high recyclability retaining 90% catalytic efficiency upto 10 reaction cycles. For long-term storage, CMS-GGT can be disinfected using either sodium azide or sodium hypochlorite solution without affecting enzyme activity. Thus, the present study provides an easy and efficient method for GGT enzyme immobilization that results in an improved and robust enzyme preparation. PMID- 27259645 TI - Chitosan-derived carbonaceous material for highly efficient adsorption of chromium (VI) from aqueous solution. AB - A carbonaceous adsorbent for effectively removing Cr(VI) was synthesized by facile hydrothermal carbonization of chitosan (HTC-chitosan). The prepared HTC chitosan exhibited good stability in acid solution while the amine groups were retained completely after simple and green hydrothermal carbonization treatment. Structure characteristics of the HTC-chitosan as well as its adsorption behaviors for Cr(VI) in aqueous solution were investigated. Under optimal conditions, the adsorption capacity of the HTC-chitosan for Cr(VI) reached as high as 388.60mgg( 1), which was much higher than that of other materials reported previously. The prepared HTC-chitosan adsorbent could be reused at least five times with adsorption efficiency more than 92%. These results indicate that HTC-chitosan exhibited great superiority for Cr(VI) adsoption from aqueous solution both in terms of the preparation process and adsorption performance. PMID- 27259646 TI - Extraction, characterization and antioxidant activity of water-soluble polysaccharides from Tuber huidongense. AB - Single-factor experiment and Box-Behnken design were employed to optimize the ultrasonic-assisted extraction (UAE) of water-soluble polysaccharides from Chinese truffle Tuber huidongense (THWP). The optimal extraction conditions with an extraction yield of 7.17+/-0.22% crude THWP were determined as follows: ultrasonic power 99.65W, extraction time 40.39min, ratio of water to raw material 24.65mL/g, and extraction temperature 70.1 degrees C. Two purified fractions, THWP-1 and THWP-2 with molecular weights of 128kDa and 729kDa, respectively, were obtained from crude THWP by Cellulose DEAE-52 and Sephadex G-100 chromatography. Monosaccharide component analysis by high performance liquid chromatography (HPLC) indicated that THWP-1 was composed of Glc, Man, and Gal with their corresponding mole percentages of 60.56%, 20.12% and 19.32%, respectively and that THWP-2 contained only Glc. Evaluation of the antioxidant activity in vitro suggested that THWP-1 and THWP-2 had effective scavenging activity of 2,2' azinobis-(3-ethylbenzothiazolin-6-sulfonicacid) (ABST), hydroxyl and 1,1-diphenyl 2-picrylhydrazyl (DPPH) radicals. Accordingly, the polysaccharides from Chinese truffle might serve as a natural antioxidant in functional foods. PMID- 27259647 TI - Production of bioactive conjugated linoleic acid by the multifunctional enolase from Lactobacillus plantarum. AB - Lactobacillus plantarum alpha-enolase, a multifunctional-anchorless-surface protein belonging to the conserved family of enolases with a central role in glycolytic metabolism, was characterized to have a side role in the intricate metabolism of biohydrogenation of linoleic acid, catalyzing the formation of bioactive 9-cis-11-trans-CLA through dehydration and isomerization of 10-hydroxy 12-cis-octadecenoic acid. The identity of the enolase was confirmed through mass spectrometric analysis that showed the characteristic 442 amino acid sequence with a molecular mass of 48.03kDa. The enolase was not capable of using linoleic acid directly as a substrate but instead uses its hydroxyl derivative 10-hydroxi 12-cis-octadecenoic acid to finally form bioactive conjugated linoleic acid. Biochemical optimization studies were carried out to elucidate the conditions for maximum production of 9-cis-11-trans-CLA and maximum stability of alpha-enolase when catalyzing this reaction. Furthermore, through structural analysis of the protein, we propose the binding sites of substrate and product molecules that were characterized as two hydrophobic superficial pockets located at opposite ends of the enolase connected through a channel where the catalysis of dehydration and isomerization might occur. These results prove that multifunctional alpha-enolase also plays a role in cell detoxification from polyunsaturated fatty acids such as linoleic acid, along with the linoleate isomerase complex. PMID- 27259648 TI - Antioxidant and hepatoprotective activities of intracellular polysaccharide from Pleurotus eryngii SI-04. AB - In present study, the intracellular polysaccharide (IPS) and its two fractions of IPS-1 and IPS-2 were obtained and purified by DEAE-52 cellulose chromatography from Pleurotus eryngii SI-04 mycelia, and their hepatoprotective effects were also investigated. The results showed that the IPS-2 had superior hepatoprotective effects by increasing the serum enzyme activities and bilirubin (BIL) levels, decreasing the serum albumin (ALB) and triglyceride (TG) levels, improving the hepatic antioxidant status, and ameliorating the hepatic structure damage. Furthermore, the monosaccharide composition and main bond types were also analyzed. These conclusions demonstrated that the both IPS and its fractions might be suitable for functional foods and natural drugs in preventing the acute liver damage. PMID- 27259649 TI - Defluoridation of water by Tea-bag model using La(3+) modified synthetic resin@chitosan biocomposite. AB - The aim of this work is to gain a better understanding of the formation of lanthanum complex onto iminodiacetic acid and chitosan (CS@La-IDAMP) composite for effective removal of fluoride from aqueous solution using a tea-bag model for the first time. The surface textural and chemical properties of the synthesized composites were characterized by FTIR, SEM with EDAX and mapping images. The experimental data revealed that the fluoride adsorption was rapid, maximum fluoride removal could be removed within 12min contact time at neutral pH in room temperature under batch equilibrium model. The equilibrium data for adsorption of fluoride on the synthesized blends were well represented by the Freundlich isotherm, giving a maximum adsorption capacity of 17.50mg/g. The adsorption kinetic models were also examined and it was found that all the sorption processes were better described by the pseudo-second-order model. This results suggested that the efficiency of the fluoride removal process was mainly controlled by electrostatic attraction and ion-exchange mechanism. Furthermore, the CS@La-IDAMP material was tested for the regeneration ability with the suitable regenerant to make this process as cost-effective. Finally, it can be concluded that the composite material is the potential adsorbent for the treatment of fluoride from water. PMID- 27259650 TI - Role of Au(III) coordination by polymer in "green" synthesis of gold nanoparticles using chitosan derivatives. AB - Here we report "green" synthesis of gold nanoparticles in solutions of heterocyclic chitosan derivatives (N-(4-imidazolyl)methylchitosan (IMC), N-2-(2 pyridyl)ethylchitosan (2-PEC), and N-2-(4-pyridyl)ethylchitosan (4-PEC)) and show how efficiency of Au(III) binding to polymer influences the Au(III) reduction rate and the size of the gold nanoparticles formed using only the reducing power of these chitosan derivatives. Rheology measurements and (1)H NMR spectroscopy data have confirmed that cleavage of glycosidic bond is a common mechanism of reducing species generation in solutions of chitosan and its N-heterocyclic derivatives. However, the emerging additional reducing species in 2-PEC and 4-PEC solutions due to vinylpyridine elimination promotes Au(III) reduction and gold nanoparticles growth despite lower efficiency of glycosidic bond cleavage in pyridyl derivatives. The decrease of the average size of gold nanoparticles in the row chitosan>2-PEC>IMC supported assumption that the increase of ligand nucleophilicity and stability of Au(III)-polymer complex results in formation of smaller nanoparticles. PMID- 27259651 TI - Factors Affecting Quality of Life at Different Intervals After Treatment of Localized Prostate Cancer: Unique Influence of Treatment Decision Making Satisfaction, Personality and Sexual Functioning. AB - PURPOSE: Using patient reported outcomes measures we identified the most informative set of factors associated with quality of life in a large sample of men treated for localized prostate cancer. MATERIALS AND METHODS: We examined relationships with quality of life using FACIT (Functional Assessment of Chronic Illness Therapy). We also hypothesized variables in a sample of men diagnosed with localized prostate cancer who represented different time points since treatment, including less than 12 months in 70, 1 to 3 years in 344, greater than 3 to 5 years in 291 and greater than 5 years in 97. Correlative measures included subscales of MAX-PC (Memorial Anxiety Scale for Prostate Cancer), short forms of PROMIS(r) and SOMS (Surgical Outcomes Measurement System), TDM-SATS (Treatment Decision-Making Satisfaction Scale) and subscales of the BFI (Big Five Inventory) of personality. RESULTS: Quality of life was significantly associated with hypothesized variables across different time cohorts. In regression models several factors accounted for most of the variability in quality of life scores depending on time since treatment, including 47%, 22%, 29% and 27% at less than 12 months, 1 to 3 years, greater than 3 to 5 years and greater than 5 years, respectively. Upon examining the unique contribution of these variables, treatment decision making satisfaction was the only variable to have a significant and unique contribution to quality of life across all 4 time cohorts (standardized coefficients 0.33, 0.27, 0.31 and 0.49, respectively, p <0.01). In the cohort with 1 to 3 years since treatment erectile function and neurotic personality style also had unique associations with quality of life (standardized coefficients 0.25 and -0.20, respectively). CONCLUSIONS: When considering the short-term and the longer term quality of life of a man after treatment for localized prostate cancer, our findings highlight the importance of treatment decision making satisfaction, erectile function and personality. PMID- 27259652 TI - The Effect of Staged Transverse Preputial Island Flap Urethroplasty for Proximal Hypospadias with Severe Chordee. AB - PURPOSE: We compare the effects of staged tranverse preputial island flap urethroplasty and the Byars 2-stage procedure in patients with proximal hypospadias and severe chordee. MATERIALS AND METHODS: We studied 87 consecutive children referred for proximal hypospadias with severe chordee between March 2011 and March 2014. Of the cases 42 were repaired with staged tranverse preputial island flap (group 1) and 45 were managed by 2-stage Byars urethroplasty (group 2). Mean +/- SD age at first stage surgery was 26.6 +/- 13.3 months in group 1 and 24.8 +/- 14.7 months in group 2. Postoperative complications in both groups were assessed regarding fistulas, urethral strictures, diverticula, meatal stenosis and glanular dehiscence. RESULTS: After the second stage 2 patients (4.8%) in group 1 and 10 (23.2%) in group 2 had urethrocutaneous fistulas (p <0.05). One patient (2.4%) in group 1 and 2 patients (4.4%) in group 2 had urethral strictures (p >0.05). All patients with stricture were cured by repeated dilation and no patient required reoperation. One patient (2.4%) in group 1 and no patient in group 2 had diverticulum (p >0.05). No patient in either group had signs or symptoms of meatal stenosis or residual chordee. Three patients (7.1%) in group 1 and 12 (26.7%) in group 2 needed reoperation (p <0.05). CONCLUSIONS: Two-stage urethroplasty, particularly tranverse preputial island flap partial urethroplasty, is appropriate for treating patients with proximal hypospadias and severe chordee. Use of the tranverse preputial island flap can decrease complications associated with the second stage and significantly improve the success rate. PMID- 27259653 TI - Factors Impacting the Occurrence of Local, Distant and Atypical Recurrences after Robot-Assisted Radical Cystectomy: A Detailed Analysis of 310 Patients. AB - PURPOSE: Peritoneal carcinomatosis and extrapelvic lymph node metastases can be seen following robot-assisted radical cystectomy. In an attempt to identify predictors of these atypical metastases we report a detailed analysis of patients treated with robot-assisted radical cystectomy in whom recurrences developed. MATERIALS AND METHODS: A total of 310 patients underwent robot-assisted radical cystectomy for bladder cancer from 2001 to 2015. Descriptive statistics were used to compare baseline variables between patients without recurrence and those with local, distant or atypical recurrence. Univariate and multivariable regression models were used to assess the effect of variables on oncologic outcomes including recurrence location. RESULTS: At a median followup of 24 months (IQR 14 51) 81 patients had recurrence. On multivariable analysis tumor classification, lymphovascular invasion, estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 and perioperative blood transfusion were significantly associated with any recurrence. Specific analyses showed that tumor and nodal classification, lymphovascular invasion and positive surgical margins were associated with all 3 recurrence locations (all p <0.05). Previous abdominal surgery was protective against atypical recurrences (HR 0.36, 95% CI 0.13-0.95, p = 0.04). Estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 and perioperative blood transfusion conferred a higher risk of distant or atypical recurrence but not of local recurrence (all p <0.05). Operative time and previous pelvic radiotherapy were not associated with any recurrence locations. CONCLUSIONS: Predictors of distant recurrences, peritoneal carcinomatosis and extrapelvic lymph node metastases after robot-assisted radical cystectomy did not significantly differ and were mainly dictated by pathological tumor characteristics. Results suggest that the risk of atypical recurrence is chiefly influenced by tumor biology rather than surgical aspects. PMID- 27259654 TI - Preventive Effects of Long-Term Caloric Restriction on Aging Related In Vivo Bladder Dysfunction and Molecular Biological Changes in the Bladder and Dorsal Root Ganglia in Rats. AB - PURPOSE: We evaluated aging related bladder dysfunctions and biological changes in the bladder and dorsal root ganglia in rats. We also investigated whether long term caloric restriction may have preventive effects on these changes. MATERIALS AND METHODS: Male Fischer 344 rats were divided into a young group (age 6 months) and an old group (age 25 to 28 months), each with free access to normal food, and an old group (age 25 to 28 months) with food restricted to 3 days per week. Conscious cystometry, cDNA microarray analysis, immunohistochemistry and oxidative stress measurements of the bladder and dorsal root ganglia were performed. RESULTS: The old group with free access to normal food showed higher threshold pressure, more nonvoiding contractions and lower bladder compliance than the young group with free access to food. Old rats with free access showed greater post-void residual volume and lower voiding efficiency than old rats with caloric restriction and young rats. In the old group with free access 83 genes in the bladder and 48 in the L6 dorsal root ganglia were up-regulated compared with old rats with caloric restriction and young rats. These genes were mostly related to immune and inflammatory responses. Immunohistochemistry showed stronger expression of the immune response protease Gzm (granzyme) B and the collagenase Mmp13 (matrix metalloproteinase-13) in the bladder of old rats with free access vs old rats with caloric restriction and young rats. The level of malondialdehyde, an oxidative stress marker, was higher in the bladder of old rats with free access than in young rats but there was no difference between old rats with caloric restriction and young rats with free access to food. CONCLUSIONS: In rats aging leads to storage and voiding dysfunctions associated with immune and inflammatory related responses in the bladder and dorsal root ganglia, and with increased oxidative stress in the bladder. Caloric restriction reduced these aging related changes. PMID- 27259655 TI - Biomarkers for Wilms Tumor: A Systematic Review. AB - PURPOSE: Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms tumor to quantify the prognostic implications of the presence of individual tumor markers. MATERIALS AND METHODS: We searched for English language studies from 1980 to 2015 performed in patients younger than 18 years with Wilms tumor and prognostic data. The protocol was conducted per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level II or III studies. RESULTS: A total of 40 studies were included examining 32 biomarkers in 7,381 patients with Wilms tumor. Studies had a median of 61 patients, 24 biomarker positive patients per series and a median followup of 68.4 months. Median percentages of patients with stages 1, 2, 3, 4 and 5 tumors were 28.5%, 26.4%, 24.5%, 14.1% and 1.7%, respectively, and 10.2% had anaplasia. The strongest negative prognostic association was loss of heterozygosity at 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity at 1p and gain of function at 1q were also strongly linked to increased recurrence (2.93 and 2.86, respectively). CONCLUSIONS: Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in patients with Wilms tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID- 27259657 TI - The Orthology Ontology: development and applications. AB - BACKGROUND: Computational comparative analysis of multiple genomes provides valuable opportunities to biomedical research. In particular, orthology analysis can play a central role in comparative genomics; it guides establishing evolutionary relations among genes of organisms and allows functional inference of gene products. However, the wide variations in current orthology databases necessitate the research toward the shareability of the content that is generated by different tools and stored in different structures. Exchanging the content with other research communities requires making the meaning of the content explicit. DESCRIPTION: The need for a common ontology has led to the creation of the Orthology Ontology (ORTH) following the best practices in ontology construction. Here, we describe our model and major entities of the ontology that is implemented in the Web Ontology Language (OWL), followed by the assessment of the quality of the ontology and the application of the ORTH to existing orthology datasets. This shareable ontology enables the possibility to develop Linked Orthology Datasets and a meta-predictor of orthology through standardization for the representation of orthology databases. The ORTH is freely available in OWL format to all users at http://purl.org/net/orth . CONCLUSIONS: The Orthology Ontology can serve as a framework for the semantic standardization of orthology content and it will contribute to a better exploitation of orthology resources in biomedical research. The results demonstrate the feasibility of developing shareable datasets using this ontology. Further applications will maximize the usefulness of this ontology. PMID- 27259659 TI - A researcher's ethical dilemma: Is self-plagiarism a condemnable practice or not? PMID- 27259658 TI - Implementing resources to support the diagnosis and management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in primary care: A qualitative study. AB - BACKGROUND: Previous research has highlighted that many GPs lack the confidence and knowledge to diagnose and manage people with CFS/ME. Following the development of an online training module for GPs, and an information pack and DVD for patients, this study explored the extent to which these resources can be implemented in routine primary care. METHODS: Semi structured qualitative interviews were completed with patients and GPs across North West England. All interviews were transcribed and analysed using open exploratory thematic coding. Following this thematic analysis, the authors conducted a further theory-driven analysis of the data guided by Normalisation Process Theory. RESULTS: When used in line with advice from the research team, the information resource and training were perceived as beneficial to both patients and GPs in the diagnosis and management of CFS/ME. However, 47 % of patients in this study did not receive the information pack from their GP. When the information pack was used, it was often incomplete, sent in the post, and GPs did not work with patients to discuss the materials. Only13 out of 21 practices completed the training module due to time pressures and the low priority placed on low prevalence, contentious, hard to manage conditions. When the module was completed, many GPs stated that it was not feasible to retain the key messages as they saw so few patients with the condition. Due to the complexity of the condition, GPs also believed that the diagnosis and management of CFS/ME should take place in a specialist care setting. CONCLUSION: While barriers to the implementation of training and resources for CFS/ME remain, there is a need to support CFS/ME patients to access reliable, evidence based information outside primary care. Our findings suggest that future research should develop an online resource for patients to support self-management. PMID- 27259660 TI - Usage patterns and attitudes towards emergency contraception: the International Emergency Contraception Research Initiative. AB - OBJECTIVES: The aim of the survey was to gain understanding of women's usage patterns and attitudes towards emergency contraception (i.e., the 'morning after pill') and to gain insight into the role and attitudes of pharmacists as providers of emergency contraception. METHODS: As part of the International Emergency Contraception Research Initiative, approximately 6500 women (15-49 years) and nearly 500 pharmacists from 14 countries in Western, Central and Eastern Europe, and Central Asia completed questionnaires via web-based interrogation or computer-assisted/paper-assisted personal interviews. RESULTS: Common to almost all countries and cultures was that, while awareness of emergency contraception was high (>=84% of respondents, except in Kazakhstan), usage was generally low (4-18%). In Austria, the Czech Republic, Spain, and the UK, better underlying protection with hormonal contraceptives or male condoms would have meant less need for emergency contraception. In Bulgaria, Lithuania, Romania, and Russia, greater dependence on less reliable contraceptive methods such as calendar + withdrawal was associated with higher use of the emergency contraceptive pill (11-18%) but also with higher abortion rates (19-21%). Overt rejection of emergency contraception in the event of an accident was low, except in countries (e.g., Austria, Poland) where the misperception that it acts as an abortifacient was common. Except for Bulgaria, pharmacists elsewhere tended to have limited knowledge and moralistic attitudes towards emergency contraception. CONCLUSIONS: Improved educational efforts, probably country-specific, are required to increase the use of highly effective methods of regular contraception and overcome barriers to acceptance of emergency contraception as a suitable postcoital solution to avoid unwanted pregnancy or abortion. PMID- 27259661 TI - Characterization of the complete mitogenomes of two Neoscona spiders (Araneae: Araneidae) and its phylogenetic implications. AB - The complete mitogenomes of two orb-weaving spiders Neoscona doenitzi and Neoscona nautica were determined and a comparative mitogenomic analysis was performed to depict evolutionary trends of spider mitogenomes. The circular mitogenomes are 14,161bp with A+T content of 74.6% in N. doenitzi and 14,049bp with A+T content of 78.8% in N. nautica, respectively. Both mitogenomes contain a standard set of 37 genes typically presented in metazoans. Gene content and orientation are identical to all previously sequenced spider mitogenomes, while gene order is rearranged by tRNAs translocation when compared with the putative ancestral gene arrangement pattern presented by Limulus polyphemus. A comparative mitogenomic analysis reveals that the nucleotide composition bias is obviously divergent between spiders in suborder Opisthothelae and Mesothelae. The loss of D arm in the trnS(UCN) among all of Opisthothelae spiders highly suggested that this common feature is a synapomorphy for entire suborder Opisthothelae. Moreover, the trnS(AGN) in araneoids preferred to use TCT as an anticodon rather than the typical anticodon GCT. Phylogenetic analysis based on the 13 protein coding gene sequences consistently yields trees that nest the two Neoscona spiders within Araneidae and recover superfamily Araneoidea as a monophyletic group. The molecular information acquired from the results of this study should be very useful for future research on mitogenomic evolution and genetic diversities in spiders. PMID- 27259662 TI - Old genes experience stronger translational selection than young genes. AB - Selection on synonymous codon usage for translation efficiency and/or accuracy has been identified as a widespread mechanism in many living organisms. However, it remains unknown whether translational selection associates closely with gene age and acts differentially on genes with different evolutionary ages. To address this issue, here we investigate the strength of translational selection acting on different aged genes in human. Our results show that old genes present stronger translational selection than young genes, demonstrating that translational selection correlates positively with gene age. We further explore the difference of translational selection in duplicates vs. singletons and in housekeeping vs. tissue-specific genes. We find that translational selection acts comparably in old singletons and old duplicates and stronger translational selection in old genes is contributed primarily by housekeeping genes. For young genes, contrastingly, singletons experience stronger translational selection than duplicates, presumably due to redundant function of duplicated genes during their early evolutionary stage. Taken together, our results indicate that translational selection acting on a gene would not be constant during all stages of evolution, associating closely with gene age. PMID- 27259663 TI - Identification of the first multi-exonic WDR72 deletion in isolated amelogenesis imperfecta, and generation of a WDR72-specific copy number screening tool. AB - Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous disorder of tooth development which is due to aberrant deposition or composition of enamel. Both syndromic and isolated forms exist; they may be inherited in an X linked, autosomal recessive, or autosomal dominant manner. WDR72 is one of ten currently known genes for recessive isolated AI; nine WDR72 mutations affecting single nucleotides have been described to date. Based on whole exome sequencing in a large consanguineous AI pedigree, we obtained evidence for presence of a multi-exonic WDR72 deletion. A home-made multiplex ligation-dependent probe amplification assay was used to confirm the aberration, to narrow its extent, and to identify heterozygous carriers. Our study extends the mutational spectrum for WDR72 to include large deletions, and supports a relevance of the previously proposed loss-of-function mechanism. It also introduces an easy-to-use and highly sensitive tool for detecting WDR72 copy number alterations. PMID- 27259664 TI - Sequence data mining in search of hookworm (Necator americanus) microRNAs. AB - The new world hookworm, Necator americanus is a soil-transmitted nematode responsible for Necatoriasis (a type of helminthiasis) in hosts such as humans, dogs, and cats. N. americanus genome and transcriptome has been sequenced and a draft assembly analysis has been published highlighting protein coding genes and possible drug target proteins. Hookworm microRNA identification, annotations and their public release is yet to be attempted. The same is evident from lack of hookworm miRNA information in related popular public nucleotide sequence repositories such as miRBase, GenBank, WormBase etc. Therefore, in the present study we addressed these issues using EST and assembled transcript sequence information of hookworm. Using computational approaches, we identified three miRNAs precursor sequences and their mature forms. We also identified their potential targets from hookworm ESTs and transcripts, and from human transcriptome. Overall, the results indicate presence of nematode specific miRNA homologs in N. americanus and shades light on their putative targets in worm itself and the human host. PMID- 27259665 TI - Analysis of the structure, evolution, and expression of CD24, an important regulator of cell fate. AB - BACKGROUND: CD24 is a small, glycophosphatidylinositol-anchored cell surface receptor, expressed in a variety of cells types and tissues. CD24 gene and protein expression is highly dynamic in response to cellular differentiation and stimulation in a cell-specific manner. Furthermore, CD24 interacts with a diverse collection of ligands, including cell adhesion molecules such as P-selectin, and the immune-associated siglec family of transmembrane proteins. While much is known regarding the biological roles of CD24 in regulating cell survival, death and differentiation, little is known about the evolution and organization of CD24 across species or the relationship between CD24 expression and its known ligands. RESULTS: We analyzed the organization and evolution of the CD24 gene from 56 mammalian, avian and reptilian species. We further examined the mRNA expression of CD24 and its known ligands in Mus musculus in immune cells, immunologically privileged tissues, developing brain, and developing and regenerating liver. CD24 arose prior to the reptilian-avian divergence and is conserved across many mammalian species, although we were unable to identify CD24 in marsupials or monotremes. The CD24 genomic structure is diverse between and within species, with varying numbers of exons, introns, and the presence of untranslated regions. Of note, we found no obvious criteria distinguishing CD24 genes from those annotated as CD24-like. The expression of CD24 is similarly complex, with immune cells showing dynamic changes in mRNA levels during development, while immunologically privileged and developing tissues show a high, static expression level that decreases in mature tissues. Furthermore, the expression of CD24 correlated with some but not all of its known ligands in a tissues-specific manner, suggesting that novel ligands have yet to be identified and that cell specific ligand expression can influence CD24 function. CONCLUSIONS: We find that CD24 arose prior to the divergence of reptiles, birds and mammals. Furthermore, the most highly conserved areas of the protein are the amino acids which can be glycosylated. We also find that CD24 expression is highly tissue-specific and in many cases, not well conserved with known CD24 ligands, suggesting yet-unknown CD24-ligand interactions. Together, these data are a valuable resource for furthering studies in CD24 biology. PMID- 27259656 TI - Cervical cancer prevention and treatment research in Africa: a systematic review from a public health perspective. AB - BACKGROUND: Women living in Africa experience the highest burden of cervical cancer. Research and investment to improve vaccination, screening, and treatment efforts are critically needed. We systematically reviewed and characterized recent research within a broader public health framework to organize and assess the range of cervical cancer research in Africa. METHODS: We searched online databases and the Internet for published articles and cervical cancer reports in African countries. Inclusion criteria included publication between 2004 and 2014, cervical cancer-related content pertinent to one of the four public health categories (primary, secondary, tertiary prevention or quality of life), and conducted in or specifically relevant to countries or regions within the African continent. The study design, geographic region/country, focus of research, and key findings were documented for each eligible article and summarized to illustrate the weight and research coverage in each area. Publications with more than one focus (e.g. secondary and tertiary prevention) were categorized by the primary emphasis of the paper. Research specific to HIV-infected women or focused on feasibility issues was delineated within each of the four public health categories. RESULTS: A total of 380 research articles/reports were included. The majority (54.6 %) of cervical cancer research in Africa focused on secondary prevention (i.e., screening). The number of publication focusing on primary prevention (23.4 %), particularly HPV vaccination, increased significantly in the past decade. Research regarding the treatment of precancerous lesions and invasive cervical cancer is emerging (17.6 %), but infrastructure and feasibility challenges in many countries have impeded efforts to provide and evaluate treatment. Studies assessing aspects of quality of life among women living with cervical cancer are severely limited (4.1 %). Across all categories, 11.3 % of publications focused on cervical cancer among HIV-infected women, while 17.1 % focused on aspects of feasibility for cervical cancer control efforts. CONCLUSIONS: Cervical cancer research in African countries has increased steadily over the past decade, but more is needed. Tertiary prevention (i.e. treatment of disease with effective medicine) and quality of life of cervical cancer survivors are two severely under-researched areas. Similarly, there are several countries in Africa with little to no research ever conducted on cervical cancer. PMID- 27259666 TI - Sex differences in DNA methylation and expression in zebrafish brain: a test of an extended 'male sex drive' hypothesis. AB - The sex drive hypothesis predicts that stronger selection on male traits has resulted in masculinization of the genome. Here we test whether such masculinizing effects can be detected at the level of the transcriptome and methylome in the adult zebrafish brain. Although methylation is globally similar, we identified 914 specific differentially methylated CpGs (DMCs) between males and females (435 were hypermethylated and 479 were hypomethylated in males compared to females). These DMCs were prevalent in gene body, intergenic regions and CpG island shores. We also discovered 15 distinct CpG clusters with striking sex-specific DNA methylation differences. In contrast, at transcriptome level, more female-biased genes than male-biased genes were expressed, giving little support for the male sex drive hypothesis. Our study provides genome-wide methylome and transcriptome assessment and sheds light on sex-specific epigenetic patterns and in zebrafish for the first time. PMID- 27259667 TI - Fibroblast growth factor receptor 1 and cytokeratin 20 expressions and their relation to prognostic variables in bladder cancer. AB - BACKGROUND: Tumor grade and stage are currently the most important prognostic variables in bladder cancer but establishing additional criteria is still needed for effective treatment. OBJECTIVES: The aim of the study was to assess the expression of fibroblast growth factor receptor 1 (FGFR1) and cytokeratin 20 (CK20) in cancer bladder (CB) and to evaluate their association with the clinicopathological features of the disease. PATIENTS AND METHODS: The study included 80 patients diagnosed as bladder cancer of different stages and grades and 80 patients with nonmalignant urothelial diseases of matched age and sex to the malignant group. The expressions of FGFR1 and CK20 in tissue samples were determined by RT-PCR and immunohistochemistry. RESULTS: The expression levels of FGFR1 and CK20 were increased in the malignant group when compared to the control group (P<0.001 for each). Analysis of their expression showed that levels of FGFR1 and CK20 were significantly higher in invasive tumor stages (pT2-pT4) than in non-invasive stages (pTis, pTa, pT1) (P<0.001). Interestingly, the sensitivity and specificity of combined detection with CK20 and FGFR1 for the differentiation between invasive and non-invasive stages of bladder cancer reached 97.5% and 92.5%, respectively. CONCLUSION: Our results determined overexpression of both FGFR1 and CK20 in CB specimens. The alterations in the expression of FGFR1 and CK20 were associated with disease stage and grade. Lastly, combined detection of FGFR1 and CK20 had a high predictive prognostic value in differentiating invasive from non-invasive carcinoma. PMID- 27259668 TI - Gene expression regulation in the plant growth promoting Bacillus atrophaeus UCMB 5137 stimulated by maize root exudates. AB - Despite successful use of Plant Growth Promoting Rhizobacteria (PGPR) in agriculture, little is known about specific mechanisms of gene regulation facilitating the effective communication between bacteria and plants during plant colonization. Active PGPR strain Bacillus atrophaeus UCMB-5137 was studied in this research. RNA sequencing profiles were generated in experiments where root exudate stimulations were used to mimic interactions between bacteria and plants. It was found that the gene regulation in B. atrophaeus UCMB-5137 in response to the root exudate stimuli differed from the reported gene regulation at similar conditions in B. amyloliquefaciens FZB42, which was considered as a paradigm PGPR. This difference was explained by hypersensitivity of UCMB-5137 to the root exudate stimuli impelling it to a sessile root colonization behavior through the CcpA-CodY-AbrB regulation. It was found that the transcriptional factor DegU also could play an important role in gene regulations during plant colonization. A significant stress caused by the root exudates on in vitro cultivated B. atrophaeus UCMB-5137 was noticed and discussed. Multiple cases of conflicted gene regulations showed scantiness of our knowledge on the regulatory network in Bacillus. Some of these conflicted regulations could be explained by interference of non-coding RNA (ncRNA). Search through differential expressed intergenic regions revealed 49 putative loci of ncRNA regulated by the root exudate stimuli. Possible target mRNA were predicted and a general regulatory network of B. atrophaeus UCMB-5137 genome was designed. PMID- 27259672 TI - The Biodefense Field. PMID- 27259669 TI - Shared care management of patients with type 2 diabetes across the primary and secondary healthcare sectors: study protocol for a randomised controlled trial. AB - BACKGROUND: The prevalence of type 2 diabetes (T2D) is growing globally and hospital-based outpatient clinics are burdened with increasing numbers of patients. To ensure high quality treatment and care, it is necessary to structurally reorganise the management of patients with T2D. The objective of this study is to test if T2D patients (who are at intermediate risk of or are already having incipient diabetic complications) jointly managed by a hospital based outpatient clinic and general practitioners (shared care programme) have a non-inferior outcome compared to an established programme in a specialised (hospital based) outpatient diabetes clinic. METHODS: The study is designed as a randomised controlled trial. The shared care model will be tested during a period of 3 years, with data collection at baseline and at 12, 24 and 36 months. All patients will be offered four medical visits a year; the shared care intervention consists of one annual comprehensive check-up at the outpatient clinic and three quarterly visits at the general practitioners' office. The control group will be followed with four quarterly visits at the outpatient clinic, including an annual comprehensive check-up. In the outpatient clinic, the patients will be treated by a specialised diabetes team, including an endocrinologist. On the basis of a predefined stratification model, we will recruit patients stratified to be at intermediate risk of or already having incipient diabetic complications. We plan to include 140 patients. The primary outcome is glycated haemoglobin. Other outcome measures include (1) the proportion of patients who meet the Danish standard indicators reflecting quality of care; (2) quality of life measured by Short Form 36; and (3) the functionality of the patients' families measured by Family Assessment Measure III. The experiences of the patients and families when participating in the shared care program will be explored by collecting dyadic interviews. DISCUSSION: This study will evaluate the quality of a shared care programme for patients with T2D, and provide evidence about advantages and disadvantages compared with a programme in a specialised outpatient clinic. The results may provide important information on how to organise the care for patients with T2D in the future. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov on 21 October 2015, registration number: NCT02586545 . PMID- 27259671 TI - Fast (40-150Hz) oscillations are associated with positive slow waves in the ictal EEGs of epileptic spasms in West syndrome. AB - OBJECTIVE: To elucidate the generative mechanisms of epileptic spasms (ESs) in West syndrome, we investigated the temporal relationship between scalp fast (40 150Hz) oscillations (FOs) and slow waves in the ictal electroencephalograms (EEGs) of ESs. METHODS: In 11 infants with WS, ictal FOs were detected in a bipolar montage based on spectral and waveform criteria. Their temporal distribution was analyzed in terms of the positive peaks (trough point, TT) of identical EEG data in a referential montage. Among six EEG data sections defined according to TT, the number of FOs, peak power values, and peak frequencies were compared. RESULTS: We identified a total of 1014 FOs (946 gamma and 68 ripple oscillations), which clustered closely at TT. The number of gamma oscillations in the 1s epoch including TT was significantly higher than those in the prior and subsequent phases. Peak power values and frequencies tended to be higher in these positive phase sections. CONCLUSIONS: The temporal association of FO clustering and positive slow waves in the ictal EEGs of ES indicated that active neuronal firing related to FOs underlies the generation of ESs and their ictal slow waves. PMID- 27259673 TI - Enhancing Beyond What Ought to be the Case - A Conceptual Clarification. AB - In order to do justice to the intuition that medical treatments as such do not form proper instances of bio-enhancement, as the notion is employed in the ethical debate, we should construe bio-enhancements as interventions, which do not aim at states that, other things being equal, ought to obtain. In the light of this clarification, we come to see that cases of moral enhancement are not covered by the notion of bio-enhancement, properly construed. PMID- 27259674 TI - Safety of treatment with high-dose daptomycin in 102 patients with infective endocarditis. AB - Daptomycin is commonly used at doses >6 mg/kg/day for various indications, including infective endocarditis (IE). A systematic assessment of skeletal muscle, renal, haematological, hepatic and pulmonary toxicity of high-dose daptomycin (HDD) in IE is lacking. A total of 102 IE patients treated with HDD were included in this non-comparative, observational, single-centre cohort study conducted from 2007 to 2014. The incidence, timing, severity and evolution of adverse events (AEs) were assessed. Patients had a median age of 61.5 years and a high prevalence of co-morbidities. Staphylococci were cultured in 87.2% of cases (62.2% meticillin-resistant). The median daptomycin dose was 8.2 mg/kg/day for a median of 20 days (range, 1-60 days). HDD was withdrawn due to AEs in 12 patients (11.8%). On-treatment death occurred in 4 cases (3.9%, none HDD-related). Muscle toxicity occurred in 15 patients in a median of 15 days after HDD starts, which was largely mild and reversible with ongoing HDD use. Mild renal toxicity was observed in 9 patients (8.8%) after a median of 12 days of HDD (RIFLE-Risk in 8, Injury in 1). A rise of peripheral blood eosinophils occurred in 16 patients (15.7%). There were three cases of eosinophilic interstitial pneumonia. Four patients (3.9%) had mild allergic or idiosyncratic reactions. No other hepatic or haematological AEs were observed. Our current experience with 102 patients suggests that HDD is safe in significantly ill IE patients with multiple co morbidities. Muscle toxicity was clinically negligible. Most importantly, there was no significant renal toxicity. Eosinophils should be carefully monitored. PMID- 27259676 TI - Prevention of recurrence of fluid collections in walled off pancreatic necrosis and disconnected pancreatic duct syndrome: Comparative study of one versus two long term transmural stents. PMID- 27259675 TI - Assessment of the vaginal residence time of biomarkers of semen exposure. AB - OBJECTIVE: The primary objective of this pilot study is to determine and compare the residence time in the vagina of biomarkers of semen exposure for up to 15 days post exposure. The biomarkers are prostate-specific antigen (PSA), Y chromosome DNA, the sex determining region of the Y chromosome (SRY) and testis specific protein Y-encoded 4 (TSPY4). The secondary objectives are to determine if biomarker concentrations differed between intercourse and inoculation groups, to establish whether the sampling frequency post exposure affected biomarker concentrations and decay profile and to determine if biomarker concentrations in vaginal swabs obtained by the participant at home were similar to swabs obtained by the nurse in the clinic. STUDY DESIGN: We randomized healthy women to unprotected intercourse (n=17) versus vaginal inoculation with the male partner's semen in the clinic (n=16). Women were then further randomized to have vaginal swabs obtained at either 7 or 4 time points after semen exposure, up to 15 days post exposure, either obtained at home by the participant or in the clinic by the research nurse. RESULTS: PSA and SRY were markers of recent semen exposure. TSPY4 was detectable in approximately 50% of participants at 15 days post exposure. Unprotected intercourse resulted in significantly higher concentrations of select biomarkers. Sampling frequency and home versus clinic sampling had no significant effect on biomarker concentrations. CONCLUSIONS: Objective biomarkers of recent or distant semen exposure may have great utility for verifying protocol compliance in a variety of clinical trials. PMID- 27259677 TI - The "tight orbit": Incidence and management of the orbital compartment syndrome. AB - PURPOSE: The orbital compartment syndrome (OCS) constitutes a severe emergency, requiring immediate clinical diagnosis and surgical decompression. The key symptom is progressive visual impairment caused by an increase in intraorbital pressure, impairing the perfusion of relevant neurovascular and neurosensory structures. Intraorbital bleeding due to trauma and surgical intervention is known to be the main etiological factor. MATERIAL AND METHODS: A retrospective analysis of all patients affected by an OCS between January 1, 2012, and May 31, 2015, was performed. Patients' records were reviewed with regard to etiology, initial ophthalmologic status, fracture pattern, concomitant medication, surgical management, and postoperative outcome. The incidence of OCS was calculated based on the total number of craniomaxillofacial (CMF) emergencies. RESULTS: Within 3.5 years, a total of 18,093 CMF emergencies were registered. In 16 patients, an OCS was documented, corresponding to an incidence of 0.088%. The mean patient age was 67.31 +/- 23.86 years, ranging from 22 to 102 years. The etiology varied, but trauma with subsequent intraorbital bleeding was the main cause. The use of anticoagulative medication was documented in 50% of the cases. In 14 patients, immediate surgical orbital decompression was performed: in 10 patients, vision could be preserved; in three patients, blindness resulted; and one patient was lost to follow-up. Two patients were managed without surgery. CONCLUSION: With regard to the total number of CMF emergencies, OCS is a rare condition. Early clinical diagnosis and surgical decompression are required to prevent permanent vision impairment. Anticoagulative medication must be considered as a predisposing factor for an orbital compartment syndrome in patients affected by periorbital trauma. PMID- 27259678 TI - Perioperative risk factors for postoperative pulmonary complications after major oral and maxillofacial surgery with microvascular reconstruction: A retrospective analysis of 648 cases. AB - BACKGROUND: Postoperative pulmonary complications (PPCs) are common and result in prolonged hospital stays, higher costs and increased mortality. However, data on the incidence and predictors of PPCs after major oral and maxillofacial surgery with microvascular reconstruction are rare. This retrospective analysis identifies perioperative risk factors for postoperative pulmonary complications (PPCs) after major oral and maxillofacial surgery with microvascular reconstruction. METHODS: Perioperative data and patient records of 648 subjects were analyzed in the period of June 2007 to May 2013. PPCs were defined as pneumonia, atelectasis, pleural effusions, pulmonary embolism, pulmonary oedema, pneumothorax or respiratory failure. RESULTS: 18.8% of all patients developed PPCs. Patient-related risk factors for PPCs were male sex, advanced age, smoking, alcohol abuse, a body mass index >30, American Society of Anaesthesiologists grade higher than 2, pre-existent pulmonary diseases and preoperative antihypertensive medication. Among the investigated procedure-related variables, the length of the operation, the amount of fluid administration and blood transfusion and an impaired oxygenation index during surgery were shown to be associated with the development of PPCs. Using a multivariable logistic regression model, we identified a body mass index >30, American Society of Anaesthesiologists grade higher than 2 and alcohol abuse as independent risk factors for PPCs. CONCLUSIONS: Several perioperative factors can be identified that are associated with the development of PPCs. Patients having one or more of these conditions should be subjected to intensified postoperative pulmonary care. PMID- 27259679 TI - How reliable is the visual appraisal of a surgeon for diagnosing orbital fractures? AB - PURPOSE: The aim of this study was to evaluate the usefulness of intra-operative visualisation, endoscopic assistance, and CT measurements for estimating the orbital fracture size and complexity. METHODS: Ten human cadaver heads were subjected to thin-slice computed tomography (CT). Standardised fractures were created using piezoelectric surgery in accordance with the Jaquiery classification system. Four surgeons and one anatomist used six different observation methods to visualise and describe the orbital defects. RESULTS: The intraclass correlation coefficients (ICCs) for the fracture length measurements were relatively low for all observation methods (range, 0.666-0.883). CT measurements of width showed high consistency (ICC, 0.910). The surface area of the defect was highly overestimated by all methods (range, 121-184%). None of the observers was able to accurately estimate the length or width of 95% of the defects within an error range of +/-0.75 cm. CONCLUSION: CT measurements are the most consistent and accurate tool for estimating the critical size of orbital factures. In daily practice, a measurement tool in a DICOM viewer could be used, although software packages that allow manual adjustments are advisable. Direct intraoperative visualisation and surgeon experience are of limited value in the estimation of fracture size and complexity, and endoscopy provides no additional advantages. PMID- 27259680 TI - Exploring physical therapists' perceptions of mobile application usage utilizing the FITT framework. AB - PRIMARY OBJECTIVE: The use of mobile apps in clinical settings is becoming a widely accepted tool for many healthcare professionals. Physical therapists (PTs) have been underresearched in this area, leaving little information regarding the challenges in using mobile apps in the PT environment. The FITT framework provides a theoretical underpinning for this investigation. RESEARCH DESIGN AND METHODS: A survey was developed based on the FITT framework and research questions. Licensed PTs in attendance at the FPTA conference were asked to complete the survey. A descriptive analysis was conducted for the study and demographic variables. A factor analysis was performed to determine the appropriateness of the FITT framework. MAIN OUTCOME AND RESULTS: The individual technology dimension showed the best fit to the framework, with the weakest fit being the individual-task dimension. The majority of PTs surveyed do not currently use apps in their professional practice nor do they feel that their organizational leadership endorses app usage. CONCLUSIONS: The integration of mobile apps into physical therapy practice can improve the standard of care. Additional apps and marketing of these apps could elevate use of this technology. However, leadership support with the necessary resources for app usage will be key to improved overall FITT. PMID- 27259681 TI - 21(st) Century Research in Child Neurology. PMID- 27259682 TI - Lateral Approach to the Distal Femoral Artery in Femoro-Anterior-Tibial Bypass Surgery. PMID- 27259683 TI - Re: 'Editor's Choice - Management of Chronic Venous Disease: Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS)'. PMID- 27259684 TI - Conversion to Gastric Bypass After Either Failed Gastric Band or Failed Sleeve Gastrectomy. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is still considered the gold standard in bariatric surgery. Before, adjustable gastric banding (AGB) was regarded as an alternative; nowadays, sleeve gastrectomy (SG) is a more favorable alternative. In case of unsatisfactory results, RYGB is often performed as a secondary procedure. Conversion of an AGB is associated with a high risk of complications; the hypothesis was that this would be less after conversion of an SG. METHODS: All patients undergoing conversion to RYGB after AGB or SG between 2005 and 2012 were included for retrospective analysis. Patient characteristics, operative details, postoperative complications, the relief of complaints, weight loss, reasons for failure, and evolution of known comorbidities up to 2 years were analyzed. RESULTS: A total of 178 patients were included (79.8 % female): AGB 110 (61.8 %) versus SG 68 (38.2 %). Main reasons for conversion were weight regain/insufficient weight loss (48.4 %) or dysphagia/reflux complaints (39.9 %). Surgical complications were found in 19 patients (AGB 13 vs SG 6; p = 0.530). Infectious complications occurred in 13 patients (AGB 11 vs SG 2; p = 0.135). Total body weight loss was equal between groups after 2 years (AGB 31.6 +/- 11.0 % vs SG 31.6 +/- 12.0 %; p = 0.998). Similar results were found in a subgroup analysis on patients undergoing conversion for additional weight loss (AGB 31.7 +/- 11.7 % vs SG 27.0 +/- 13.1 %; p = 0.173). CONCLUSIONS: Conversion to RYGB after failed AGB or SG showed comparable short-term results in terms of postoperative complications and weight loss. PMID- 27259685 TI - Reply to the Article Chen CY. et al. "Laparoscopic Conversion of Gastric Bypass Complication to Sleeve Gastrectomy: Technique and Early Results." Obes Surg. 2016 Jan 19. [Epub ahead of Print]. PMID- 27259687 TI - Flexibility and Stability Trade-Off in Active Site of Cold-Adapted Pseudomonas mandelii Esterase EstK. AB - Cold-adapted enzymes exhibit enhanced conformational flexibility, especially in their active sites, as compared with their warmer-temperature counterparts. However, the mechanism by which cold-adapted enzymes maintain their active site stability is largely unknown. In this study, we investigated the role of conserved D308-Y309 residues located in the same loop as the catalytic H307 residue in the cold-adapted esterase EstK from Pseudomonas mandelii. Mutation of D308 and/or Y309 to Ala or deletion resulted in increased conformational flexibility. Particularly, the D308A or Y309A mutant showed enhanced substrate affinity and catalytic rate, as compared with wild-type EstK, via enlargement of the active site. However, all mutant EstK enzymes exhibited reduced thermal stability. The effect of mutation was greater for D308 than Y309. These results indicate that D308 is not preferable for substrate selection and catalytic activity, whereas hydrogen bond formation involving D308 is critical for active site stabilization. Taken together, conformation of the EstK active site is constrained via flexibility-stability trade-off for enzyme catalysis and thermal stability. Our study provides further insights into active site stabilization of cold-adapted enzymes. PMID- 27259686 TI - Contribution of concentration-sensitive sodium channels to the absorption of alveolar fluid in mice. AB - The concentration-sensitive sodium channel (Nac) is activated by an increase in the extracellular sodium concentration. Although the expression of Nac in alveolar type II epithelial cells (AEC II) has been reported previously, the physiological role of Nac in the lung has not been established. We characterized Nac expression and examined amiloride-insensitive sodium transport mediated by Nac in mouse lung. Immunofluorescence studies revealed that Nac did not colocalize with either aquaporin 5 or cystic fibrosis transmembrane conductance regulator, but partially colocalized with the epithelial sodium channel gamma subunit. Immunoelectron microscopy studies showed that Nac localized at the basolateral membrane of pulmonary microvascular endothelial cells (PMVECs). Nac mRNA and protein were expressed in PMVECs isolated from the lungs of mice. Image analysis indicated that sodium influx into the alveolar wall was dependent on increases in extracellular sodium concentration. We conclude that Nac expressed in PMVECs and AEC II contributes to the reabsorption of sodium via an amiloride insensitive pathway during alveolar fluid clearance. PMID- 27259688 TI - Role of Autophagy in Hypoxia-Induced Angiogenesis of RF/6A Cells in vitro. AB - PURPOSE: Autophagy plays a role in the pathogenesis of tumor angiogenesis and cardiovascular diseases. The autophagy level in mammalian cells was found to increase in the state of hypoxia or ischemia reperfusion. However, the role of autophagy in ocular angiogenesis has not yet been elucidated. The aim of this study was to investigate the effects of autophagy on hypoxia-induced choroidal and retinal angiogenesis in vitro using a rhesus macaque choroid-retinal endothelial (RF/6A) cell line. MATERIALS AND METHODS: RF/6A cells were cultured and randomly divided into three groups according to the different culture media: control, hypoxia model[adding 125MUMcobalt chloride (CoCl2) to the culture medium], and hypoxia with an autophagy inhibition group [pretreatment with 5 mmol/L 3-methyladenine (3-MA) for 1.5 h and then adding125MUmol/LCoCl2 to the culture medium]. The impact of 3-MA's effect on the level of autophagy proteins (Beclin-1 and LC3) was tested by Western blot analysis. The cell proliferation was assessed using the chromogenicmethylthiazol tetrazolium bromide (MTT) dye after 24 and 48 hours. Cell migration was investigated by wound assay. The tube formation was measured on Matrigel. RESULTS: Under chemical hypoxia conditions, Beclin-1 and LC3 levels increased and this change can be inhibited by 3-MA. Cell viability was decreased in cells treated with CoCl2 for 24 and 48 h compared with the control, and pretreatment with 3-MA slightly promoted CoCl2-inhibited cell proliferation. Cell migration and tube formation were increased in cells treated with CoCl2 for 24 and 48 h compared with the control. Pretreatment with 3-MA significantly inhibited CoCl2-induced cell migration and tube formation. CONCLUSIONS: Hypoxia-induced autophagy decreased the cell viability and increased the cell migration and tube formation of RF/6A cells. 3-MA can inhibit hypoxia induced angiogenesis of RF/6A cells in vitro. The present study suggests that autophagy plays a role in retinal and choroidal angiogenesis and the autophagy inhibitor can be a potential candidate for the treatment of choroidal or retinal neovascularization. PMID- 27259689 TI - Targeting highly expressed extracellular HSP90 in breast cancer stem cells inhibits tumor growth in vitro and in vivo. AB - Breast cancer stem cells (BCSC) have been identified in breast carcinoma as CD44(+)/CD24(-/low) cells, which display tumorigenic activity and have the ability to self-renew, differentiate and metastasize. Previous studies showed that extracellular HSP90 (eHSP90) participates in the invasion and metastatic processes of various cancers including breast cancer. Here, we show for the first time that eHSP90 is over-expressed in mammosphere cultures that are derived from the MDA-MB-231, MDA-MB-453 and MCF-7 breast cancer cell lines. These mammospheres are highly enriched in cells of the CD44(+)/CD24(-/low) BCSC phenotype and additionally show high expression of the BCSC markers CD49f and Sox2. Thus our results indicate that eHSP90 represents a potential novel BCSC marker. Moreover, we present evidence that eHSP90 is functionally involved in BCSC activity in vitro and in vivo. Selective neutralization of eHSP90, using the monoclonal antibody mAb 4C5, has the capacity to inhibit stem cell activity in vitro because the formation of mammosphere-derived colonies is dramatically reduced in its presence. In vivo, the treatment of mice with mAb4C5 using a prophylactic protocol, significantly inhibited the primary growth of MDA-MB-231 and mammosphere-derived tumors. More importantly, administration of this antibody in a therapeutic protocol caused a statistically significant regression of established tumors derived from MDA-MB-231 originating mammospheres. Tumor regression was even greater when mAb 4C5 was administered in combination with paclitaxel. Overall, our findings implicate eHSP90 as a potential novel BCSC biomarker. Moreover they show that eHSP90 participates in BCSC-derived primary tumor growth. Finally, we provide additional support for the possible therapeutic value of mAb4C5 in the treatment of breast cancer. PMID- 27259690 TI - Oceanihabitans sediminis gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from the Yellow Sea. AB - A Gram-stain-negative, rod-shaped bacterial strain, designated S9-10T, was isolated from a sediment sample from the Yellow Sea near China. Phylogenetic analysis of 16S rRNA gene sequences revealed that strain S9-10T was a member of the family Flavobacteriaceaeand formed a distinct lineage. The genomic DNA G+C content of strain S9-10T was 34.2 mol%. The major respiratory quinone was MK-6. The predominant cellular fatty acids were iso-C15 : 0 (21.1 %), iso-C15 : 1G (16.3 %) and iso-C17 : 0 3-OH (12.0 %). The polar lipid profile contained phosphatidylethanolamine, aminophospholipid, aminoglycolipid, two unidentified aminolipids and five unidentified polar lipids. On the basis of phenotypic, genotypic, chemotaxonomic and phylogenetic analyses, strain S9-10T represents a novel species of a novel genus of the family Flavobacteriaceae, for which the name Oceanihabitans sediminis gen. nov., sp. nov. is proposed. The type strain of Oceanihabitans sediminis is S9-10T (=DSM 28133T =LMG 28074T). PMID- 27259691 TI - G protein-coupled receptor160 regulates mycobacteria entry into macrophages by activating ERK. AB - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, invades and replicates within susceptible hosts by disturbing host antimicrobial mechanisms. Although G protein-coupled receptors (GPCRs) are involved in most physiological and pathological activities of mammalian cells, the roles of GPCRs in Mtb invasion into host cell remain elusive. Here, we report that GPR160 expression is elevated at both mRNA and protein level in macrophages in response to BCG infection. Both the PiggyBac (PB) transposon-mediated mutation of gpr160 gene in mouse primary macrophages and siRNA-mediated knockdown of GPR160 in the human macrophage cell line THP-1 markedly reduced the entry of green fluorescent protein (GFP) expressing BCG (BCG-GFP), also operative in vivo. BCG infection induced phosphorylation of ERK1/2 was significantly reduced in gpr160 mutated (gpr160(-/-)) macrophages relative to levels observed in wild type macrophages, while inhibition of ERK by specific inhibitor or knockdown ERK1/2 by specific siRNA markedly reduced entry of BCG. Finally, lower bacteria burdens and attenuated pathological impairments were observed in the lungs of BCG-infected gpr160(-/-) mice. Furthermore, gpr160(-/-) macrophages also exhibits reduced uptake of Escherichia coli and Francisella tularensis. Taken together, these findings suggest an important role of GPR160 in regulating the entry of BCG into macrophages by targeting the ERK signaling pathway. As GPCRs have proven to be successful drug targets in pharmaceutical industry, it's tempting to speculate that compounds targeting GPR160, a G protein-coupled receptor, could intervene in Mtb infection. PMID- 27259694 TI - Analysis of gene copy number changes in head and neck cancer. AB - OBJECTIVE: Chromosomal alterations and copy number changes are frequent events in tumors, leading to amplification of focal regions containing several oncogenes. Gains and losses of several regions have been reported in head and neck cancer (HNC) but the copy number changes of the individual genes located in these regions have not been analyzed so far. In this study we aimed to analyze the copy number variations in patients with HNC. DESIGN: Prospective study SETTING: University hospital PARTICIPANTS: 50 patients with squamous cell carcinoma of the head and neck METHODS: Copy number changes and amplifications of 22 genes in tumors and matched tissue were analyzed by MLPA which allows simultaneous analysis of gene copy numbers in multiple genetic regions. RESULTS: Amplifications were observed in 52% and losses were detected in 20% of the samples. Chromosome 8 was found to harbor the most frequent copy number alterations. The most frequently amplified genes were CCND1 and the MED1 genes followed by the MTDH and MYC genes on the long arm and ZNF703 on the short arm of chromosome 8. Amplification of the ZNF703, PRDM14 and MYC genes were highly correlated suggesting that the genes displaying high copy number changes on chromosome 8 collaborate during carcinogenesis. CONCLUSIONS: The alterations found in our study supports the contribution of gene amplifications and indicate cooperation between certain oncogenes in the pathogenesis of HNSCC. Correlations between amplification of less familiar genes and known oncogenes warrant further investigation. This article is protected by copyright. All rights reserved. PMID- 27259692 TI - Is there a significant interaction effect between apolipoprotein E rs405509 T/T and epsilon4 genotypes on cognitive impairment and gray matter volume? AB - BACKGROUND: Evidence demonstrates that the T allele of the single-nucleotide polymorphism rs405509 in the apolipoprotein E (APOE) promoter is a risk factor for Alzheimer's disease. However, it is unknown whether rs405509 T allele synergizes with the APOE epsilon4 allele in influencing cognition and brain structure. METHODS: We analyzed the interaction effect of the rs405509 T allele and the APOE epsilon4 allele on cognitive ability and brain gray matter volume among elderly people. The subjects were grouped into four groups according to APOE and rs405509 genotypes. RESULTS: Significant interaction effects were found between rs405509 and APOE on general mental status, memory and attention. Analysis of the whole brain gray matter showed a significantly positive interaction effect between rs405509and APOE on the right inferior temporal gyrus and right fusiform gyrus (alphasim correction P < 0.001). In addition, there was a significant relationship between cognitive ability and gray matter volume. CONCLUSIONS: The data indicate that the APOE rs405509 T homozygote modulates the effect of APOE epsilon4 on both cognitive performance and brain gray matter structure. PMID- 27259693 TI - Beneficial effect of Lactococcus lactis NCC 2287 in a murine model of eosinophilic esophagitis. AB - BACKGROUND: Eosinophilic esophagitis (EoE) is a severe inflammatory disease of the esophagus which is characterized histologically by an eosinophilic infiltration into the esophageal tissue. The efficacy of probiotics in the context of atopic diseases has been well investigated but, to date, there has been no study which has evaluated probiotic effects on EoE inflammation. This study sought to identify a probiotic which improves esophageal inflammation in experimental EoE. METHODS: Two candidate probiotics, Lactococcus lactis NCC 2287 and Bifidobacterium lactis NCC 2818, were tested in a murine model of EoE elicited by epicutaneous sensitization with Aspergillus fumigatus protein extract. Administration of bacterial strains in drinking water was used, respectively, as a preventive or treatment measure, or continuously throughout the study. Inflammatory parameters were assessed in the esophagus, skin, and lungs after allergen challenge. RESULTS: In this EoE model, supplementation with L. lactis NCC 2287 significantly decreased esophageal and bronchoalveolar eosinophilia but only when given as a therapeutic treatment. No significant effect on eosinophilia was observed when NCC 2287 was given as a preventive or a continuous intervention. NCC 2287 supplementation had no significant effect on immunoglobulin levels, skin symptom scores, or on transepidermal water loss. Supplementation with another probiotic, B. lactis NCC 2818, had no significant effect on esophageal eosinophilia. CONCLUSION: We identified a L. lactis strain, able to attenuate esophageal eosinophilic inflammation in a preclinical model of EoE. This effect is strain specific and depends on the timing and duration of bacterial supplementation. Confirmation of these observations in human clinical trials is warranted. PMID- 27259695 TI - Checkpoint Blockade - a New Treatment Paradigm in Renal Cell Carcinoma. AB - Nivolumab is the first checkpoint inhibitor for the treatment of renal cell carcinoma (RCC), which is in line for approval in Europe. Despite its novelty in the treatment algorithm of RCC, it offers a whole new strategy of therapy management with safe applicability. The aim of this work was to review current data on checkpoint inhibitors in RCC and discuss future perspectives for this novel approach in RCC. A selective literature search was performed in the Pubmed database: Nivolumab is a first-in-class agent for the treatment of RCC, and its European label is anticipated for 2016. Contrary to many other agents, nivolumab was able to show a benefit in overall survival and health-related quality of life when compared to everolimus. Current trials focus on optimizing and expanding its use to metastatic RCC. In conclusion, nivolumab has already acquired a role in the treatment algorithm of RCC. However, which patient population derives the most benefit as well its optimal use in the treatment algorithm remain to be determined. A number of ongoing trials will provide novel insights and might help to untangle this novel network of therapy management for immunotherapies. PMID- 27259696 TI - Bullying of Surgery Residents and Attending Staff Surgeons is a Problem! PMID- 27259697 TI - Idiopathic facial aseptic granuloma: case report and literature review. PMID- 27259698 TI - Advancing haematopoietic stem and progenitor cell biology through single-cell profiling. AB - Haematopoietic stem and progenitor cells (HSPCs) sit at the top of the haematopoietic hierarchy, and their fate choices need to be carefully controlled to ensure balanced production of all mature blood cell types. As cell fate decisions are made at the level of the individual cells, recent technological advances in measuring gene and protein expression in increasingly large numbers of single cells have been rapidly adopted to study both normal and pathological HSPC function. In this review we emphasise the importance of combining the correct computational models with single-cell experimental techniques, and illustrate how such integrated approaches have been used to resolve heterogeneities in populations, reconstruct lineage differentiation, identify regulatory relationships and link molecular profiling to cellular function. PMID- 27259699 TI - Relationship Between Obesity, Hypertension, and Aldosterone Production in Postmenopausal African American Women: A Pilot Study. AB - Increased abdominal obesity is associated with increased cardiovascular risk, especially in African American women. The adipocyte is documented to produce a number of inflammatory factors including the hormone aldosterone. There are very few data documenting aldosterone production from adipocytes of postmenopausal women as well as data demonstrating the effects of angiotensin receptor blockade (ARB) on its production in predominately African American women. The authors hypothesize that increased central adipocyte mass in obese postmenopausal women contributes to increased production of aldosterone that is suppressed with the ARB azilsartan medoxomil. The authors tested this hypothesis in a double-blind, placebo-controlled pilot study of 34 hypertensive postmenopausal women (mean age 57.5+/-7.5 years), 91% of whom were African American. Patients had a mean 24-hour ambulatory systolic blood pressure of 127+/-13 mm Hg off any blocker of the renin angiotensin system but while taking other antihypertensive medications. The authors further validated aldosterone production in a nested cohort of women using fat cells from a fat pad biopsy. Azilsartan reduced 24-hour urinary aldosterone by 47.3% from baseline (P=.03), with between-groups differences in urine aldosterone of -5.3+/-52.3% placebo vs -47.3+/-32.9% azilsartan (P=.07) at 6 months. An adrenal cell line treated with adipocyte-conditioned media from subcutaneous abdominal adipocytes of postmenopausal women (n=3) showed an increase in aldosterone production blocked by an ARB (1948+/-1297 pg/mL fat alone vs 894+/-438 pg/mL fat + ARB; P=.022). The authors conclude that aldosterone is produced from subcutaneous adipocytes of obese postmenopausal women. Moreover, use of an ARB significantly reduces aldosterone production within 6 months of use in these women as well as in cells exposed to their adipocytes. PMID- 27259700 TI - Longitudinal study of DNA methylation during the first 5 years of life. AB - BACKGROUND: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. METHODS: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina((r)) Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. RESULTS: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. CONCLUSIONS: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention. PMID- 27259701 TI - RNF8 promotes epithelial-mesenchymal transition of breast cancer cells. AB - BACKGROUND: Epithelial-mesenchymal transition (EMT) is a crucial step for solid tumor progression and plays an important role in cancer invasion and metastasis. RNF8 is an ubiquitin E3 ligase with RING domain, and plays essential roles in DNA damage response and cell cycle regulation. However the role of RNF8 in the pathogenesis of breast cancer is still unclear. METHODS: The expression of RNF8 was examined in different types of breast cell lines by Western Blotting. EMT associated markers were examined by Immunofluorescence and Western Blotting in MCF-7 when RNF8 was ectopically overexpressed, or in MDA-MB-231 when RNF8 was depleted. Transwell and wound healing assays were performed to assess the effect of RNF8 on cell mobility. The xenograft model was done with nude mice to investigate the role of RNF8 in tumor metastasis in vivo. Breast tissue arrays were used to examine the expression of RNF8 by immunohistochemistry. Kaplan-Meier survival analysis for the relationship between survival time and RNF8 signature in breast cancer was done with an online tool ( http://kmplot.com/analysis/ ). RESULTS: RNF8 is overexpressed in highly metastatic breast cancer cell lines. Overexpression of RNF8 in MCF-7 significantly promoted EMT phenotypes and facilitated cell migration. On the contrary, silencing of RNF8 in MDA-MB-231 induced MET phenotypes and inhibited cell migration. Furthermore, we proved that these metastatic behavior promoting effects of RNF8 in breast cancer was associated with the inactivation of GSK-3beta and activation of beta-catenin signaling. With nude mice xenograft model, we found that shRNA mediated downregulation of RNF8 reduced tumor metastasis in vivo. In addition, we found that RNF8 expression was higher in malignant breast cancer than that of the paired normal breast tissues, and was positively correlated with lymph node metastases and poor survival time. CONCLUSIONS: RNF8 induces EMT in the breast cancer cells and promotes breast cancer metastasis, suggesting that RNF8 could be used as a potential therapeutic target for the prevention and treatment of breast cancer. PMID- 27259702 TI - Intestinal-type gastric adenocarcinoma without Helicobacter pylori infection successfully treated with endoscopic submucosal dissection. AB - A 67-year-old woman was admitted to our hospital for further examination and for treatment of gastric neoplasia located on the posterior wall of the antrum of the stomach, as revealed by screening esophagogastroduodenoscopy. The patient had no history of Helicobacter pylori (H. pylori) eradication. Her serum H. pylori antibody and urea breath test results were negative, histopathological findings revealed no H. pylori bacteria, and endoscopic findings revealed no chronic gastritis. We performed endoscopic submucosal dissection (ESD). Histological examination of the resected tissues revealed the tumor to be composed of a well differentiated tubular adenocarcinoma with a tubular-type adenoma confined to the mucosa. This adenocarcinoma exhibited immunohistochemical expression of CD10, MUC2, and Cdx2, but not MUC5AC or MUC6. This is an extremely rare case of H. pylori infection-negative, intestinal-type, differentiated gastric adenocarcinoma revealed by detailed immunohistochemical examination that was treated with ESD. The patient has had no recurrence of adenocarcinoma after ESD. PMID- 27259704 TI - Major components of orange oil inhibit Staphylococcus aureus growth and biofilm formation, and alter its virulence factors. AB - Bovine mastitis is a costly disease in the dairy industry and does not always respond to antibiotic treatment. The major components of terpeneless, cold pressed Valencia orange oil - citral, linalool, decanal and valencene - were examined as potential alternative treatments for Staphylococcus aureus-associated mastitis. The minimum inhibitory concentration (MIC) of all four components against S. aureus was determined after incubation for 24 h. Growth inhibition assays were performed for all effective components on S. aureus for either a 3 h or 72 h treatment. These components were tested for the ability to disrupt pre formed S. aureus biofilms after 24 h of treatment by measuring absorbance at 540 nm. Cytotoxicity against immortalized bovine mammary epithelial (MAC-T) cells was measured using an MTT assay following a 1 h exposure. Only concentrations below the 50 % cytostatic concentration (CC50) were used in an adherence and invasion assay of S. aureus on MAC-T cells, and for measurements of virulence and biofilm gene expression via qPCR. The MICs of citral and linalool were 0.02 % and 0.12 %, respectively, but decanal and valencene were ineffective. Citral and linalool were capable of inhibiting growth of S. aureus after 24 h at their MIC values and inhibited pre-formed biofilms of S. aureus . The concentrations below the CC50 were 0.02 % for citral and 0.12 % for linalool. These concentrations inhibited the adhesion and invasion ability of S. aureus and downregulated virulence genes. Only 0.12 % linalool downregulated the expression of S. aureus biofilm-forming genes. These components should be considered for further in vivo study. PMID- 27259705 TI - [Sinking incidence of dementia]. PMID- 27259703 TI - Pedunculated-type T1 colorectal carcinoma with lung carcinoma metastasis at the deepest invasive portion. AB - We present a rare case of colorectal T1 carcinoma with metastasis of previous lung carcinoma found at the deepest invasive portion. A 61-year-old man presented with cervical lymphadenopathy 18 years after undergoing surgery for right lung carcinoma [poorly differentiated adenocarcinoma stage IIb (T3N0M0)]. Contrast enhanced computed tomography showed enlarged lymph nodes (LNs) in the neck and mediastinal regions. Combined hybrid-F-fluorodeoxyglucose positron emission computerized tomography showed increased radionuclide uptake in multiple cervical LNs and mediastinal LNs. LN biopsy revealed a poorly differentiated adenocarcinoma, suspected to be a metastatic tumor of the lung. Subsequent colonoscopy revealed a pedunculated-type lesion with a depressed area in the ascending colon. We performed polypectomy as total excisional biopsy; this tumor was composed mainly of moderately differentiated adenocarcinoma, partially mixed with mucinous adenocarcinoma. The pathological findings of the invasive front of the colorectal carcinoma showed poorly differentiated adenocarcinoma with a morphological pattern similar to that of the previous lung carcinoma. Furthermore, immunohistochemical results for the histological type of the deepest invasive portion of the tissue specimen were positive for thyroid transcription factor-1 but negative for Caudal-type homeobox 2. From these morphological and immunohistochemical findings, the final diagnosis was moderately differentiated lung carcinoma, pTX N3 M1b (LN, colon) Stage IV. PMID- 27259706 TI - Robot deployment in long-term care : Case study on using a mobile robot to support physiotherapy. AB - BACKGROUND: Healthcare systems in industrialized countries face the challenge of providing care for a growing number of elderly people. Information technology has the possibility of facilitating this process by providing support for nursing staff and improving the well-being of the elderly through a variety of support systems. OBJECTIVE: Little is known about the challenges that arise from the deployment of technology in care settings; however, the integration of technology into care is one of the core determinants of successful support. This article presents the challenges and options associated with the integration of technology into care using the example of a mobile robot to support physiotherapy for elderly people with cognitive impairment in the European project Spatio-Temporal Representations and Activities for Cognitive Control in Long-Term Scenarios (STRANDS). RESULTS AND DISCUSSION: This article presents the technical challenges associated with the introduction of robots in the context of care as well as the perspectives of physiotherapists involved and an overview of information and experiences gained. It is hoped that this will provide useful information for the work of researchers and practitioners wishing to integrate robotic aids into the caregiving process. PMID- 27259707 TI - [The De Morton Mobility Index for evaluation of early geriatric rehabilitation]. AB - BACKGROUND: The timed up and go (TUG) test and the Tinetti test are most frequently used in Germany to document the success of rehabilitation in early geriatric rehabilitation. However, there has been some uncertainty whether these instruments can describe the entire spectrum of mobility with adequate precision and whether they can be successfully applied for repeated assessments during rehabilitation. Against this background the De Morton Mobility Index (DEMMI) has been developed and validated. OBJECTIVE: The aim of this study was to evaluate the suitability of the DEMMI compared to the TUG and Tinetti tests in early geriatric rehabilitation. MATERIAL AND METHODS: Ceiling and floor effects of the DEMMI, the TUG test, the Tinetti test and the Barthel Index (BI) were determined. Correlations were calculated using the Spearman correlation coefficient. Effects on the DEMMI were estimated through multiple linear regression. RESULTS: A total of 144 patients with an average age of 84.91 years (SD +/-5.77) and 65.97 % females participated in this study. The mean value for the DEMMI was 33.45 (SD +/ 15.37) points at admission and 43.90 (SD +/-15.55) at discharge (n = 144). Floor effects were observed in the TUG test in 84.72 % (n = 122) of patients at admission and in 60.42 % (n = 87) at discharge. The DEMMI, Tinetti test and BI showed no floor or ceiling effects. The correlation between the DEMMI and the TUG test was -0.48 at admission and -0.49 at discharge, between the DEMMI and the Tinetti test 0.75 and 0.82, respectively and between the DEMMI and the BI 0.54 and 0.66, respectively (p < 0,01). CONCLUSION: Significant correlations with the TUG test, the Tinetti test and the BI, together with the lack of floor and ceiling effects provide evidence that the DEMMI is an appropriate tool to assess mobility in early geriatric rehabilitation. The lack of floor and ceiling effects appears to make the DEMMI a superior tool compared to the TUG test. PMID- 27259708 TI - Polyetheretherketone (PEEK) for medical applications. AB - Polyetheretherketone (PEEK) is a polyaromatic semi-crystalline thermoplastic polymer with mechanical properties favorable for bio-medical applications. Polyetheretherketone forms: PEEK-LT1, PEEK-LT2, and PEEK-LT3 have already been applied in different surgical fields: spine surgery, orthopedic surgery, maxillo facial surgery etc. Synthesis of PEEK composites broadens the physicochemical and mechanical properties of PEEK materials. To improve their osteoinductive and antimicrobial capabilities, different types of functionalization of PEEK surfaces and changes in PEEK structure were proposed. PEEK based materials are becoming an important group of biomaterials used for bone and cartilage replacement as well as in a large number of diverse medical fields. The current paper describes the structural changes and the surface functionalization of PEEK materials and their most common biomedical applications. The possibility to use these materials in 3D printing process could increase the scientific interest and their future development as well. PMID- 27259709 TI - First in man study of EP217609, a new long-acting, neutralisable parenteral antithrombotic with a dual mechanism of action. AB - EP217609 is a parenteral antithrombotic compound combining in one molecule an indirect anti-factor Xa inhibitor, a direct thrombin active site inhibitor and a biotin moiety. AIMS: The aim of the study is to investigate the safety, pharmacokinetics and pharmacodynamics of single ascending intravenous doses of EP217609. METHODS: In this randomised double-blind placebo-controlled study, healthy male subjects were administered intravenously single ascending doses (1, 3 or 10 mg) of EP217609 or placebo. Each treatment group consisted of 10 subjects of whom 8 received EP217609 and 2 received placebo. RESULTS AND CONCLUSIONS: All doses of EP217609 were well tolerated. A total of five treatment-emergent adverse events were reported, all considered unrelated, but no bleedings or other significant adverse events occurred during this study. In both plasma and urine, there was a strong correlation between EP217609 concentrations as measured by anti-factor IIa and Xa specific bioassays indicating that the two pharmacological activities of EP217609 did not dissociate in vivo. EP217609 pharmacokinetics were dose proportional and characterised by a low clearance, a small volume of distribution and a terminal half-life of 20.4 h. The long half-life was reflected in long-lasting, dose-dependent effects on activated and ecarin clotting time, thrombin and prothrombin time, activated partial thromboplastin time, thrombin generation time and anti-factor Xa activity. Pharmacokinetic/pharmacodynamic modelling indicated that the concentration of EP217609 producing 50 % of the pharmacodynamic effect was 3400 and 2210 ng/mL for activated clotting time and anti-factor Xa activity, respectively. These results warranted further clinical development of EP217609. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * There is a limited number of neutralisable anticoagulants, particularly when rapid neutralisation is required. * Synthetic anti-Xa compounds have predictable pharmacokinetic profiles. However, problems with thrombin rebound remain because of the inability to inhibit clot-bound thrombin. WHAT THIS STUDY ADDS: * This manuscript provides a comprehensive investigation of the pharmacokinetics, pharmacodynamics and safety of EP217609, and the results were the basis of future clinical studies in both healthy subjects and patients. * The pharmacokinetic/pharmacodynamic modelling provided information for dose selection in such future studies. PMID- 27259710 TI - Detection of Shiga toxin-producing and other diarrheagenic Escherichia coli by the BioFire FilmArray(r) Gastrointestinal Panel in human fecal samples. AB - The purpose of this investigation was the evaluation of the performance of the BioFire FilmArray(r) Gastrointestinal (FA-GI) Panel, a multiplexed molecular stool screening assay, for the detection of diarrheagenic Escherichia coli (DEC), with emphasis on Shiga toxin-producing E. coli (STEC). A dilution series of 12 STEC reference strains was tested with the FA-GI Panel to assess the analytical sensitivity. A total of 389 patient samples were analyzed with the FA-GI Panel and confirmation of the detected DEC was attempted with an in-house culture-based polymerase chain reaction (PCR) method. All Shiga toxin genes, except the one encoding Stx2f, were detected in bacterial dilutions ranging from 10(4) to 10(2) colony-forming units (CFU)/ml. eae + stx2f + STEC was misclassified as enteropathogenic E. coli (EPEC). Different sensitivities for various gene targets present in one isolate led to differing identifications depending on the concentration. Using the in-house method as a reference, the FA-GI Panel had a sensitivity of 90.6 % [confidence interval (CI) 75.0 %-98.0 %] and a specificity of 97.2 % (CI 94.9 %-98.6 %) for STEC detection in feces. At least one DEC was reported in 35.5 % (171/389) of the patient specimens, with EPEC being the most prevalent (n = 71). Only 59.7 % of the detected DEC could be confirmed, presumably because the comparator method was not applied directly on feces. The FA-GI Panel could not detect the stx2f subtype, misclassified certain pathogens, and the high detection rate of EPEC needs further investigation. Nevertheless, we believe that this sensitive and convenient system will prove to be an invaluable tool for the rapid diagnosis of most DEC infections, but culturing of the detected microorganisms should always be attempted. PMID- 27259711 TI - Comparative evaluation of two fully-automated real-time PCR methods for MRSA admission screening in a tertiary-care hospital. AB - We evaluated two fully-automated real-time PCR systems, the novel QIAGEN artus MRSA/SA QS-RGQ and the widely used BD MAX MRSA assay, for their diagnostic performance in MRSA admission screening in a tertiary-care university hospital. Two hundred sixteen clinical swabs were analyzed for MRSA DNA using the BD MAX MRSA assay. In parallel, the same specimens were tested with the QIAGEN artus MRSA/SA QS-RGQ. Automated steps included lysis of bacteria, DNA extraction, real time PCR and interpretation of results. MRSA culture was additionally performed as a reference method for MRSA detection. Sensitivity values were similar for both assays (80 %), while the QIAGEN artus MRSA/SA QS-RGQ reached a slightly higher specificity (95.8 % versus 90.0 %). Positive (PPVs) and negative predictive values (NPVs) were 17.4 % and 99.4 % for the BD MAX MRSA assay and 33.3 % and 99.5 % for the QIAGEN artus MRSA/SA QS-RGQ, respectively. Total turn around time (TAT) for 24 samples was 3.5 hours for both assays. In conclusion, both assays represent reliable diagnostic tools due to their high negative predictive values, especially for the rapid identification of MRSA negative patients in a low prevalence MRSA area. PMID- 27259712 TI - Spread of carbapenem-resistant international clones of Acinetobacter baumannii in Turkey and Azerbaijan: a collaborative study. AB - Epidemic clones of Acinetobacter baumannii, described as European clones I, II, and III, are associated with hospital epidemics throughout the world. We aimed to determine the molecular characteristics and genetic diversity between European clones I, II, and III from Turkey and Azerbaijan. In this study, a total of 112 bloodstream isolates of carbapenem-resistant Acinetobacter spp. were collected from 11 hospitals across Turkey and Azerbaijan. The identification of Acinetobacter spp. using conventional and sensitivity tests was performed by standard criteria. Multiplex polymerase chain reaction (PCR) was used to detect OXA carbapenemase-encoding genes (bla OXA-23-like, bla OXA-24-like, bla OXA-51 like, and bla OXA-58-like). Pulsed-field gel electrophoresis (PFGE) typing was used to investigate genetic diversity. The bla OXA-51-like gene was present in all 112 isolates, 75 (67 %) carried bla OXA-23-like, 7 (6.2 %) carried bla OXA-58 like genes, and 5 (4.5 %) carried bla OXA-24-like genes. With a 90 % similarity cut-off value, 15 clones and eight unique isolates were identified. The largest clone was cluster D, with six subtypes. Isolates from clusters D and I were widely spread in seven different geographical regions throughout Turkey. However, F cluster was found in the northern and eastern regions of Turkey. EU clone I was grouped within J cluster with three isolates found in Antalya, Istanbul, and Erzurum. EU clone II was grouped in the U cluster with 15 isolates and found in Kayseri and Diyarbakir. The bla OXA-24-like gene in carbapenemases was identified rarely in Turkey and has been reported for the first time from Azerbaijan. Furthermore, this is the first multicenter study in Turkey and Azerbaijan to identify several major clusters belonging to European clones I and II of A. baumannii. PMID- 27259714 TI - HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naive, HER2-positive, locally advanced/metastatic breast cancer. AB - BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab - however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody liposomal doxorubicin conjugate that specifically targets HER2-overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naive, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations. METHODS/DESIGN: HERMIONE is an open label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naive patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab. DISCUSSION: The HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02213744 . Registration date: 06AUG2014. PMID- 27259715 TI - FAK Expression, Not Kinase Activity, Is a Key Mediator of Thyroid Tumorigenesis and Protumorigenic Processes. AB - There are limited therapy options for advanced thyroid cancer, including papillary and anaplastic thyroid cancer (PTC and ATC). Focal adhesion kinase (FAK) regulates cell signaling by functioning as a scaffold and kinase. Previously, we demonstrated that FAK is overexpressed and activated in thyroid cancer cells and human PTC clinical specimens. However, it remains unclear whether patients with advanced thyroid cancer will benefit from FAK inhibition. Therefore, the dual functions of FAK in mediating protumorigenic processes and thyroid tumorigenesis were investigated. Evidence here shows that FAK expression predominantly regulates thyroid cancer cell growth, viability, and anchorage independent growth. FAK inhibition, with PF-562,271 treatment, modestly reduced tumor volumes, while FAK depletion, through shRNA knockdown, significantly reduced tumor volumes in vivo A role for FAK expression in tumor establishment was demonstrated in a model of PTC, where FAK knockdown tumors did not develop. FAK depletion also led to a significant decrease in overall metastatic burden. Interestingly, pretreatment with a FAK inhibitor resulted in a paradoxical increase in metastasis in a model of ATC, but decreased metastasis in a model of PTC. These data provide the first evidence that FAK expression is critical for the regulation of thyroid tumorigenic functions. IMPLICATIONS: This study demonstrates that FAK expression, but not kinase activity alone, predominantly mediates thyroid tumor growth and metastasis, indicating that targeting the scaffolding function(s) of FAK may be an important therapeutic strategy for advanced thyroid cancer, as well as other FAK-dependent tumors. Mol Cancer Res; 14(9); 869-82. (c)2016 AACR. PMID- 27259716 TI - DNA Methylome Analyses Implicate Fallopian Tube Epithelia as the Origin for High Grade Serous Ovarian Cancer. AB - High-grade serous ovarian cancer (HGSC) is the most common and lethal form of epithelial ovarian cancer (EOC). Two distinct tissues have been suggested as the tissue of origin: ovarian surface epithelia (OSE) and fallopian tube epithelia (FTE). We hypothesized that the DNA methylome of HGSC should more closely resemble the methylome of its tissue of origin. To this end, we profiled HGSC (n = 10), and patient-matched OSE and FTE (n = 5) primary fresh-frozen tissues, and analyzed the DNA methylome using Illumina 450K arrays (n = 20) and Agilent Sure Select methyl-seq (n = 7). Methylomes were compared using statistical analyses of differentially methylated CpG sites (DMC) and differentially methylated regions (DMR). In addition, methylation was evaluated within a variety of different genomic contexts, including CpG island shores and Homeobox (HOX) genes, due to their roles in tissue specification. Publicly available HGSC methylome data (n = 628) were interrogated to provide additional comparisons with FTE and OSE for validation. These analyses revealed that HGSC and FTE methylomes are significantly and consistently more highly conserved than are HGSC and OSE. Pearson correlations and hierarchal clustering of genes, promoters, CpG islands, CpG island shores, and HOX genes all revealed increased relatedness of HGSC and FTE methylomes. Thus, these findings reveal that the landscape of FTE more closely resembles HGSC, the most common and deadly EOC subtype. IMPLICATIONS: DNA methylome analyses support the hypothesis that HGSC arise from the fallopian tube and that due to its tissue-specificity and biochemical stability, interrogation of the methylome may be a valuable approach to examine cell/tissue lineage in cancer. Mol Cancer Res; 14(9); 787-94. (c)2016 AACR. PMID- 27259718 TI - Regional differences of standardised mortality rates for ischemic heart diseases in the Slovak Republic for the period 1996-2013 in the context of income inequality. AB - BACKGROUND: The aim of paper is to analyse the development of standardised mortality rates for ischemic heart diseases in relation to the income inequality in the regions of Slovakia. This paper assesses different types of income indicators, such as mean equivalised net income per household, Gini coefficient, unemployment rate, at risk of poverty threshold (60 % of national median), S80/S20 and their effect on mortality. METHODS: Using data from the Slovak mortality database 1996-2013, the method of direct standardisation was applied to eliminate variances resulted from differences in age structures of the population across regions and over time. To examine the relationships between income indicators and standardised mortality rates, we used the tools of descriptive statistics and methods of correlation and regression analysis. RESULTS: At first, we show that Slovakia has the worst values of standardised mortality rates for ischemic heart diseases in EU countries. Secondly, mortality rates are significantly higher for males compared with females. Thirdly, mortality rates are improving from Eastern Slovakia to Western Slovakia; additionally, high differences in the results of variability are seen among Slovak regions. Finally, the unemployment rate, the poverty rate and equivalent disposable income were statistically significant income indicators. CONCLUSIONS: Main contribution of paper is to demonstrate regional differences between mortality and income inequality, and to point out the long-term unsatisfactory health outcomes. PMID- 27259717 TI - SIX1 Oncoprotein as a Biomarker in a Model of Hormonal Carcinogenesis and in Human Endometrial Cancer. AB - The oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in several human cancer types but has not been investigated in human endometrial cancer. In a model of hormonal carcinogenesis, mice neonatally exposed to the soy phytoestrogen genistein (GEN) or the synthetic estrogen diethylstilbestrol (DES) develop endometrial cancer as adults. Previously, we demonstrated that SIX1 becomes aberrantly expressed in the uteri of these mice. Here, we used this mouse model to investigate the role of SIX1 expression in endometrial carcinoma development and used human tissue microarrays to explore the utility of SIX1 as a biomarker in human endometrial cancer. In mice neonatally exposed to GEN or DES, the Six1 transcript level increased dramatically over time in uteri at 6, 12, and 18 months of age and was associated with development of endometrial carcinoma. SIX1 protein localized within abnormal basal cells and all atypical hyperplastic and neoplastic lesions. These findings indicate that developmental estrogenic chemical exposure induces persistent endometrial SIX1 expression that is strongly associated with abnormal cell differentiation and cancer development. In human endometrial tissue specimens, SIX1 was not present in normal endometrium but was expressed in a subset of endometrial cancers in patients who were also more likely to have late stage disease. These findings identify SIX1 as a disease biomarker in a model of hormonal carcinogenesis and suggest that SIX1 plays a role in endometrial cancer development in both mice and women. IMPLICATIONS: The SIX1 oncoprotein is aberrantly expressed in the endometrium following developmental exposure to estrogenic chemicals, correlates with uterine cancer, and is a biomarker in human endometrial cancers. Mol Cancer Res; 14(9); 849-58. (c)2016 AACR. PMID- 27259719 TI - Gender inequalities in mental wellbeing in 26 European countries: do welfare regimes matter? AB - BACKGROUND: Nature and extent of welfare regimes and social policies are important determinants of health and health inequalities. This study examines the association of gender and mental wellbeing in European countries and investigates whether type of welfare regime plays a role in this association. METHOD: Data of 19 366 women and 14 338 men of the third round of the European Quality of Life Survey (2011-12) was used to analyse mental wellbeing, assessed by the World Health Organization 5-Mental Wellbeing Index. Multilevel logistic regression analyses were performed to analyse the association between gender and good mental wellbeing first at country-level, and secondly the between country variation was analysed and welfare regimes were included as explanatory variables. RESULTS: We observed cross-national variation in good mental wellbeing. At country levels gender inequalities in good mental wellbeing were observed in 7 out of 26 countries. In analyses considering all countries together gender inequalities in good mental wellbeing were identified independent of further individual socio demographic variables and independent of the welfare regimes that people lived in [women vs. men: OR = 0.76; (95% CI = 0.71-0.81)]. Gender inequalities in good mental wellbeing were not modified by welfare regimes. CONCLUSION: There are cross-national differences in good mental wellbeing between European countries. Gender inequalities with a lower prevalence of good mental wellbeing among women are common in European countries. This study suggests that welfare regimes do not modify these gender inequalities in mental wellbeing. PMID- 27259720 TI - Occupational, social and medical characteristics of early prenatal leave in France. AB - BACKGROUND: In France, most women of childbearing age work. The prenatal leave law in France protects women during pregnancy and their employment. We aimed to describe how long before delivery women stopped working and analyse the association between occupational, social and medical factors and early prenatal leave (before 24 weeks' gestation). METHODS: The sample was extracted from the 2010 French National Perinatal Survey. Women were interviewed in French maternity units during a 1-week period. We focused on all women with a singleton live birth who were working during pregnancy (n = 10 149). Women were interviewed between delivery and discharge to collect information on employment, date of leave, sociodemographic and medical characteristics. RESULTS: Among women who worked during pregnancy, 27.5% reported early occupational leave (before 24 weeks' gestation). Early occupational leave was more frequent among women with unstable jobs (fixed-term vs. non-fixed-term contract: adjusted odds ratio aOR = 1.60 [95% confidence interval 1.40-1.84]) and with less-qualified occupational categories (manual workers vs. managers and upper-intellectual positions: aOR = 2.96 [2.30 3.82]), even after adjusting for sociodemographic and other employment characteristics. Women with a pathological or at risk pregnancy left work earlier than other women. After stratification on type of pregnancy there was still a higher rate of early leave for women with less qualified occupational group. CONCLUSION: In France, social vulnerability of pregnant women, linked to low sociodemographic situation or low occupational categories, is associated with early leave during pregnancy, even after stratification on type of pregnancy. PMID- 27259721 TI - Inclusion of migrants and ethnic minorities in European birth cohort studies-a scoping review. AB - BACKGROUND: Migrant and ethnic minority groups constitute substantial parts of European populations. They frequently experience health disadvantages relative to the respective majority populations. Birth cohort studies can help to disentangle social and biological factors producing these health inequalities over the life course. We investigated whether birth cohorts in European countries (i) assess migration history and ethnicity in the study design; and (ii) use this information in data analyses. METHODS: A scoping review was performed in which European birth cohort studies were identified using dedicated web-based registries, MEDLINE and EMBASE. Two reviewers systematically assessed all identified birth cohorts and selected those fulfilling defined inclusion criteria (e.g. enrolment after 1980). Publications and websites were screened for information on the inclusion of migrants and ethnic minorities. To obtain more detailed information, researchers of enrolled birth cohorts were contacted individually. RESULTS: Eighty-eight birth cohorts were identified in 20 European countries, with more than 486 250 children enrolled in total. Sixty-two studies (70.5%) reported collecting data about migration history or ethnic background. Twenty-three studies (26%) used information on migration history or ethnicity for data analyses or plan to do so in future. CONCLUSION: The majority of European birth cohorts assessed participants' migration history or ethnic background; however, this information was seldom used for comparative analyses in trying to disentangle reasons for health inequalities. Also, heterogeneous indicators were used. Better use of data already available, as well as harmonization of data collection on migration history and ethnicity, could yield interesting insights into the production of health inequalities. PMID- 27259722 TI - Trends and predictors of knowledge about HIV/AIDS and its prevention and transmission methods among women in Tajikistan. AB - BACKGROUND: Prior research on HIV infections in Tajikistan and other Central Asian countries has focused primarily on injection drug users. Given the recent rise of heterosexual transmission, especially among women, there is a need to assess women's knowledge about HIV/AIDS and its methods of prevention and transmission across two time periods to examine cross-time changes and identify areas that need improvements. METHODS: Logistic regression and simulation of predicted probability analyses were based on data from Tajik women ranging in age from 15 to 49 who participated in the Multiple Indicator Cluster Survey (MICS) study in 2000 and 2005. RESULTS: We found that an over 2-fold increase in general knowledge about HIV/AIDS was accompanied by a substantial decrease in the ability to identify correct methods of prevention and to reject myths regarding its transmission. CONCLUSION: These alarming findings should prompt policy makers and program implementers to shift the focus of programs from raising general awareness to educating women about how HIV/AIDS is transmitted. Furthermore, rigorous efforts should be made to provide the most disadvantaged groups, including women of younger ages, with lower education, and from poor households with accurate information and adequate access to limited resources. PMID- 27259723 TI - Single point mutations enhance activity of cis-epoxysuccinate hydrolase. AB - OBJECTIVES: To enhance activity of cis-epoxysuccinate hydrolase from Klebsiella sp. BK-58 for converting cis-epoxysuccinate to tartrate. RESULTS: By semi saturation mutagenesis, all the mutants of the six important conserved residues almost completely lost activity. Then random mutation by error-prone PCR and high throughput screening were further performed to screen higher activity enzyme. We obtained a positive mutant F10D after screening 6000 mutations. Saturation mutagenesis on residues Phe10 showed that most of mutants exhibited higher activity than the wild-type, and the highest mutant was F10Q with activity of 812 U mg(-1) (k cat /K m , 9.8 +/- 0.1 mM(-1) s(-1)), which was 230 % higher than that of wild-type enzyme 355 U mg(-1) (k cat /K m , 5.3 +/- 0.1 mM(-1) s(-1)). However, the thermostability of the mutant F10Q slightly decreased. CONCLUSIONS: The catalytic activity of a cis-epoxysuccinate hydrolase was efficient improved by a single mutation F10Q and Phe10 might play an important role in the catalysis. PMID- 27259724 TI - Genetic transformation of rare Verbascum eriophorum Godr. plants and metabolic alterations revealed by NMR-based metabolomics. AB - OBJECTIVES: To develop a protocol to transform Verbascum eriophorum and to study the metabolic differences between mother plants and hairy root culture by applying NMR and processing the datasets with chemometric tools. RESULTS: Verbascum eriophorum is a rare species with restricted distribution, which is poorly studied. Agrobacterium rhizogenes-mediated genetic transformation of V. eriophorum and hairy root culture induction are reported for the first time. To determine metabolic alterations, V. eriophorum mother plants and relevant hairy root culture were subjected to comprehensive metabolomic analyses, using NMR (1D and 2D). Metabolomics data, processed using chemometric tools (and principal component analysis in particular) allowed exploration of V. eriophorum metabolome and have enabled identification of verbascoside (by means of 2D-TOCSY NMR) as the most abundant compound in hairy root culture. CONCLUSION: Metabolomics data contribute to the elucidation of metabolic alterations after T-DNA transfer to the host V. eriophorum genome and the development of hairy root culture for sustainable bioproduction of high value verbascoside. PMID- 27259725 TI - Enhancement of production and activity of alkaline zinc metalloprotease from Salinivibrio proteolyticus using low intensity direct electric current and zinc nanoparticles. AB - OBJECTIVES: To improve the production and activity of an alkaline zinc metalloprotease from Salinivibrio proteolyticus in response to ZnSO4 (ionic and nanoparticle forms) and low intensity direct electric current (LIDC). RESULTS: A DC of 50 uA for 10 min increased enzyme production from 35 to 53 U ml(-1) when applied to the stationary phase bacterial cells. Zn(2+) improved enzyme production better than zinc nanoparticles (52 vs. 43.5 U ml(-1)). Zinc nanoparticles (0.5 mM) added to an enzyme reaction mixture containing casein (0.65 %) and 20 mM Tris/HCl buffer (pH 8) improved enzyme activity more than Zn(2+) (42 vs. 36 U ml(-1)). CONCLUSION: LIDC exposure (50 uA, 10 min) to the stationary phase bacterial cells increases metalloprotease production in Salinivibrio. A low concentration of zinc nanoparticles (0.5 mM) increases maximum enzyme activity. PMID- 27259726 TI - Engineering Vibrio fischeri transcriptional activator LuxR for diverse transcriptional activities. AB - OBJECTIVES: To alter DNA binding specificity of Vibrio fischeri LuxR and to expand the toolbox for constructing synthetic networks. RESULTS: A mutation library (about 10,000 individuals) of the DNA binding domain of LuxR were generated. A genetic selection was performed to obtain LuxR mutants that recognize three lux box DNA variants that are not recognized by wild-type LuxR. Six LuxR mutants were identified. The evolved LuxR mutants were further characterized by measuring the transcriptional activities of different combinations of LuxR mutants and lux box variants. Varied transcriptional activities were found in these LuxR-lux box pairs. The background expressions of the evolved LuxR-lux box systems are more tightly regulated than the wild-type LuxR-lux box system. CONCLUSION: The LuxR transcriptional system was evolved to recognize three lux box DNAs which are not recognized by wild-type LuxR. PMID- 27259727 TI - Collection of Samples for DNA Analysis. AB - Effective sampling of biological material is critical to the ability to acquire DNA profiles of probative value. The main methods of collection are swabbing, tapelifting, or direct excision. This chapter describes the key aspects to consider when applying these methods, in addition to suggested procedures for swabbing and tapelifting. Important issues to be considered, such as exhibit triaging, pre-examination preparation, contamination risk reduction, sample localization, sample identification, and sample prioritization as well as aspects of record keeping, packaging, and storage, are also raised. PMID- 27259728 TI - Body Fluid Identification Using mRNA Profiling. AB - RNA analysis is a valuable tool for the identification of the forensically relevant body fluids, saliva, blood, menstrual blood, cervicovaginal fluid, and semen. Multiple human mRNA and bacterial RNA markers have been identified for each of these body fluids. RNA and DNA can be coextracted from the same portion of a sample and RNA markers for different body fluids can be multiplexed in a single PCR, thereby maximizing the number of analyses that can be performed with limited sample material. PMID- 27259729 TI - mRNA Profiling for Vaginal Fluid and Menstrual Blood Identification. AB - Recently mRNA profiling has been widely proposed as a universal tool for biological fluids identification. Here, we describe a test for vaginal fluid identification that combines detection of five markers: vaginal mRNAs and Lactobacilli in end-point PCR reaction. The test detects the following transcripts: HBD1 (Human beta-defensin 1), MUC4 (Mucin 4), MMP11 (Matrix metalloproteinase 11), housekeeping gene G6PDH (glucose 6-phosphate dehydrogenase), and the 16S-23S rRNA intergenic spacer regions of L. crispatus and L. gasseri/L. johnsonii. Simultaneous analysis of five vaginal markers and a housekeeping gene ensures high specificity and reliability in the detection of vaginal material, which could not be obtained using detection of a single marker. PMID- 27259730 TI - Preservation of and DNA Extraction from Muscle Tissue. AB - As well as protecting DNA for subsequent analysis, tissue preservation methods ideally should be safe, readily available, and easy to transport at relatively low cost. Formalin (formaldehyde solution), used extensively to preserve medical and museum specimens, irreparably damages DNA. We have found four tissue preservatives (solid salt, salt-saturated dimethyl sulfoxide (DMSO)-EDTA solution, ethanol solution, and ethanol-EDTA solution) that preserved muscle tissue at 35 degrees C for up to 1 month: full short tandem repeat (STR) profiles were obtained after preservation. In addition, salt-saturated DMSO-EDTA solution yielded full STR profiles from aliquots of the liquid preservative surrounding muscle tissue. PMID- 27259731 TI - DNA Extraction: Organic and Solid-Phase. AB - DNA extraction remains a critical step in DNA profiling of biological material recovered from scenes of crime. In the forensic community several methods have gained popularity, including Chelex((r)), organic extraction, and solid-phase extraction. While some laboratories streamlined their processes and only use one method we have retained several methods and continue to use these for different sample types. In this chapter we present three methods that have been used for several years in our laboratory. PMID- 27259732 TI - Extraction of DNA from Skeletal Remains. AB - Acquisition of DNA from skeletal remains can be a delicate process. With the advent of improved extraction buffers that provide complete demineralization of the osseous materials, extraction of total genomic DNA from nearly any skeletal element is possible. This chapter describes both traditional organic and more newly developed inorganic extraction methods for fresh and dried skeletal remains. PMID- 27259733 TI - Extraction of DNA from Human Skeletal Material. AB - In recent years the recovery and analysis of DNA from skeletal remains has been applied to several contexts ranging from disaster victim identification to the identification of the victims of conflict. Here are described procedures for processing the bone and tooth samples including mechanical and chemical cleaning, cutting and powdering in the presence of liquid nitrogen, complete demineralization of bone and tooth powder, DNA extraction, DNA purification using magnetic beads, and the precautions and strategies implemented to avoid and detect contamination. It has proven highly successful in the analysis of bones and teeth from Second World War victims' skeletal remains that have been excavated from mass graves in Slovenia and is also suitable for genetic identification of relatively fresh human remains. PMID- 27259734 TI - The Development and Use of Internal Amplification Controls (IACs) with DNA Profiling Kits for Forensic DNA Analysis. AB - Biological samples recovered for forensic investigations are often degraded and/or have low amounts of DNA; in addition, in some instances the samples may be contaminated with chemicals that can act as PCR inhibitors. As a consequence this can make interpretation of the results challenging with the possibility of having partial profiles and false negative results. Because of the impact of DNA analysis on forensic investigations, it is important to monitor the process of DNA profiling, in particular the amplification reaction. In this chapter we describe a method for the in-house generation and use of internal amplification controls (IACs) with DNA profiling kits to monitor the success of the PCR proces. In the example we show the use of the SGM Plus(r) kit. These controls can also be used to aid the interpretation of the DNA profile. PMID- 27259735 TI - NucleoSpin((r)) XS Columns for DNA Concentration and Clean-Up. AB - The phenol-chloroform (organic) extraction method continues to be a preferred method for extraction of DNA from forensic evidence samples that may contain low quantities of DNA and polymerase chain reaction (PCR) inhibitors. The aqueous extracts from the organic extraction of DNA require subsequent concentration and cleanup, which has traditionally been performed with microdialysis filter units, including the Centricon((r)) and Microcon((r)) centrifugal filter devices. Here, we describe the use of the NucleoSpin((r)) XS silica columns as an alternative for the concentration and purification of the aqueous extracts from the organic extraction and for the removal of PCR inhibitors from existing DNA extracts. PMID- 27259736 TI - Purification of PCR Products to Improve STR Profiles. AB - Forensic laboratories routinely perform STR analyses using commercially available STR kits. Very low levels of DNA are extracted from many forensic samples. In these samples, the amount of DNA that can be placed in a PCR is below the optimal DNA range for the commercial kits, leading to weak profiles and allelic dropout. STR profiles generated from poor quality samples can be improved by purification of the PCR product prior to capillary electrophoresis. PMID- 27259737 TI - Analysis of 30 Biallelic INDEL Markers Using the Investigator DIPplex((r)) Kit. AB - Insertion/deletion polymorphisms (INDELs) are a relatively new class of a DNA marker to be used in forensic casework; used most commonly as a supplementary method to STR-based typing. INDELs, like SNPs, are particularly useful for the analysis of highly degraded DNA as the amplicon sizes are typically below 160 bp; they can also be valuable as an additional tool to help resolve kinship cases, with the advantage over STRs that they do not have high mutation rates. INDELs have an advantage over SNPs in that they are length polymorphisms and so can be analyzed by simply measuring the length of the allele(s). The Qiagen Investigator((r)) DIPplex Kit is currently only one of two commercially available kits for the amplification of INDEL polymorphisms; it amplifies 30 biallelic INDEL loci and the amelogenin locus. The primers used are fluorescence labeled with 6-FAM, BTG, BTY, and BTR. This technique is robust, relatively simple, and the results are analyzed using the same capillary electrophoresis equipment and software as used for STR typing. PMID- 27259738 TI - Analysis of Mitochondrial Control Region Using Sanger Sequencing. AB - The analysis of mitochondrial DNA (mtDNA) is an established forensic tool and has been used extensively to aid with both the identification of human remains and evidence recovered from scenes of crime. The biology of mtDNA confers both advantages and disadvantages when using it as a tool for identification. It benefits from a high copy number, which facilitates analysis from samples with highly degraded DNA or trace amounts of DNA, but the maternal mode of inheritance restricts its power of discrimination. With Next Generation Sequencing being used in research and some forensic casework laboratories the scope of mtDNA analysis in forensic casework may expand in the near future. Currently, however, most casework laboratories rely on Sanger sequencing and an established method for analyzing the hypervariable sequence regions is described. PMID- 27259739 TI - Whole Human Mitochondrial DNA Sequencing. AB - Mitochondrial DNA (mtDNA) can help in the identification of biological evidence recovered from crime scenes and human remains. Typically the hypervariable regions are targeted for sequencing; however, more discriminating profiles are obtained if the whole genome is sequenced. Different approaches exist as to how best amplify and sequence whole mtDNA from forensic specimens. Here, we describe a method based on two-round PCR, combining multiplex and simplex PCRs. This method has been used in the analysis of mitochondrial genomes from archival saliva samples applied to FTA(r) cards after 10 years of transportation and preservation, without special protection. It is expected that this technique can be also used for the analysis of other old biological specimens directly or with modifications related to the level of DNA degradation. PMID- 27259740 TI - In-Solution Hybridization for the Targeted Enrichment of the Whole Mitochondrial Genome. AB - A detailed protocol is presented for the targeted enrichment of whole mitochondrial genomes based on an in-solution hybridization strategy. Bait is produced in-house by sonication of two long-range PCR amplicons and ligation of biotinylated double-stranded adapters. Indexed target DNA is hybridized with the bait in a multiplex enrichment reaction and pulled down using magnetic streptavidin beads followed by subsequent post-enrichment PCR and sequencing on an Illumina MiSeq. This strategy removes the need for expensive commercial bait probes while allowing enrichment of multiple samples in a single hybridization reaction. The method is particularly suitable for degraded DNA as it is able to enrich short DNA fragments and is not susceptible to polymerase artifacts introduced during PCR-based assays. PMID- 27259741 TI - Enhanced DNA Profiling of the Semen Donor in Late Reported Sexual Assaults: Use of Y-Chromosome-Targeted Pre-amplification and Next Generation Y-STR Amplification Systems. AB - In some cases of sexual assault the victim may not report the assault for several days after the incident due to various factors. The ability to obtain an autosomal STR profile of the semen donor from a living victim rapidly diminishes as the post-coital interval is extended due to the presence of only a small amount of male DNA amidst an overwhelming amount of female DNA. Previously, we have utilized various technological tools to overcome the limitations of male DNA profiling in extended interval post-coital samples including the use of Y chromosome STR profiling, cervical sample, and post-PCR purification permitting the recovery of Y-STR profiles of the male DNA from samples collected 5-6 days after intercourse. Despite this success, the reproductive biology literature reports the presence of spermatozoa in the human cervix up to 7-10 days post coitus. Therefore, novel and improved methods for recovery of male profiles in extended interval post-coital samples were required. Here, we describe enhanced strategies, including Y-chromosome-targeted pre-amplification and next generation Y-STR amplification kits, that have resulted in the ability to obtain probative male profiles from samples collected 6-9 days after intercourse. PMID- 27259742 TI - Analysis of Rapidly Mutating Y Chromosome Short Tandem Repeats (RM Y-STRs). AB - Rapidly mutating (RM) Y-STRs were recently identified and can help to differentiate between paternally related males in paternity and forensic casework. Normal Y-STRs are often used in casework due to their paternal inheritance, which can help to resolve kinship cases, and identify male components in male/female mixtures; however, more discriminating profiles are obtained if rapidly mutating Y-STRs are used. Previously two or three multiplex PCRs have been used to amplify 13 RM Y-STRs; here, an assay amplifying these 13 markers in a single multiplex PCR is described. Commercially available male control DNA samples have been genotyped during the validation of this assay, thus providing a tool for calibrating genotyping results. It is expected that the assay will provide a niche tool for genotyping casework samples. PMID- 27259743 TI - A Practical Guide to the HIrisPlex System: Simultaneous Prediction of Eye and Hair Color from DNA. AB - The HIrisPlex system, which consists of two parts, allows the simultaneous prediction of eye and hair color from DNA, e.g., samples extracted from crime scene evidence. The first part is a highly sensitive multiplex genotyping assay consisting of 24 DNA markers using SNaPshotTM chemistry, for analysis on all Capillary Electrophoresis machines. The second part consists of statistical models that respectively establish eye and hair color prediction probabilities from complete and incomplete genotype profiles using parameters generated from large genotype and phenotype databases. This combined prediction tool constitutes the online system freely available to users. Here we provide a practical guide on how to use the HIrisPlex system for forensic and other DNA applications. PMID- 27259744 TI - Inference of Ancestry in Forensic Analysis I: Autosomal Ancestry-Informative Marker Sets. AB - An expanding choice of ancestry-informative marker single nucleotide polymorphisms (AIM-SNPs) is becoming available for the forensic user in the form of sensitive SNaPshot-based tests or in alternative single-base extension genotyping systems (e.g., Sequenom iPLEX) that can be adapted for analysis with SNaPshot. In addition, alternative ancestry-informative variation: Indels and STRs can be analyzed using direct PCR-to-CE techniques that offer the possibility to detect mixed profiles. We review the current forensically viable AIM panels, their optimized PCR multiplexes, and the population differentiation power they offer. We also describe how improved population divergence balance can be achieved with the enlarged multiplex scales of next-generation sequencing approaches to enable analysis of admixed individuals without biased estimation of co-ancestry proportions. PMID- 27259745 TI - Inference of Ancestry in Forensic Analysis II: Analysis of Genetic Data. AB - Three approaches applicable to the analysis of forensic ancestry-informative marker data-STRUCTURE, principal component analysis, and the Snipper Bayesian classification system-are reviewed. Detailed step-by-step guidance is provided for adjusting parameter settings in STRUCTURE with particular regard to their effect when differentiating populations. Several enhancements to the Snipper online forensic classification portal are described, highlighting the added functionality they bring to particular aspects of ancestry-informative SNP analysis in a forensic context. PMID- 27259746 TI - Species Determination: The Role and Use of the Cytochrome b Gene. AB - The illegal trade in ivory and rhino horn has led to a catastrophic decline in elephant and rhino populations worldwide. These iconic high profile species are one part of the illegal trade in wildlife products that threatens these species and the ecological balance in the habitats in which they live. Identification of the species present is required to determine that the trade is illegal and contrary to national legislation. This chapter details a robust DNA technique using part of the cytochrome b gene on the mitochondrial genome that will work on poor quality samples such as powdered horn or ivory products including statues and carvings. An appropriate DNA extraction technique is required to obtain at least 1 ng of DNA from which the amplification of part of the cytochrome b gene using universal primers is performed. This produces a fragment of 486 bp in size which can be sequenced using standard technologies. The resulting sequences are then aligned to voucher specimens or sequences on reliable databases. Analyses of the data should lead to confident species identification. PMID- 27259747 TI - Effect of positive airway pressure on glomerular filtration rate in patients with sleep-disordered breathing: a meta-analysis. AB - OBJECTIVE: Sleep-disordered breathing (SDB) has been suggested to be associated with chronic kidney disease (CKD). Positive airway pressure (PAP) is an effective treatment for SDB, but the impact of PAP therapy on glomerular filtration rate (GFR) in patients with SDB remains unclear. The present meta-analysis was performed to determine whether PAP therapy could increase GFR. DESIGN: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed for literature published up to January 2016. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-PAP therapy. RESULTS: A total of eight studies with 240 patients were pooled into a meta-analysis. The meta-analysis showed that there was no change of GFR before and after PAP treatment in SDB patients (SMD = 0.010, 95 % confidence interval (CI) = -0.331 to 0.350, z = 0.06, p = 0.956), Subgroup analyses indicated that GFR was significantly increased after PAP treatment in elder patients (>=55 years) (SMD = -0.283, 95 % CI = -0.518 to -0.047, z = 2.35, p = 0.019) and patients with therapeutic duration >= 3 months (SMD = -0.276, 95 % CI = -0.522 to -0.031, z = 2.20, p = 0.027). CONCLUSION: The present meta-analysis suggested that PAP treatment had no impact on GFR in SDB patients. However, longer PAP usage for SDB patients significantly improved GFR. In elder SDB subjects, PAP was also associated with a statistically significant increase in GFR. PMID- 27259749 TI - Experimental evidence that sperm maturation drives protandry in an ectotherm. AB - Protandry, i.e., the earlier arrival to breeding areas of males than females, has attracted a lot of scientific attention. However, evidence for the evolutionary hypotheses of protandry is surprisingly scarce. Here, we experimentally manipulate the time of emergence from hibernation of males, relative to females, in the common lizard, Zootoca vivipara. We test whether the timing of emergence affects sperm maturation and mating success, to disentangle among proposed selective advantages of protandry. Our results experimentally demonstrate that the timing of emergence affects the date of sperm presence. Moreover, the degree of protandry affected whether males had sperm upon their first encounter with females, but it did not affect the probability of copulating. Mating occurred independent of male fertility and mating during infertility was least common in early emerging males. Early emergence from hibernation by males, relative to females, thus increases the male's chance of fertilising eggs and later emergence from hibernation by females reduces the female's probability of mating with infertile males. These results point to direct reproductive benefits of protandry in males and females, where earlier emergence is predicted to increase the male's opportunities to inseminate mates, and later emergence reduces the female's probability of copulating with infertile males. This suggests that protandry evolved due to the time required for sperm maturation after emergence from hibernation. PMID- 27259748 TI - Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson's disease. AB - PURPOSE: Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). METHODS: In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. RESULTS: For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p < 0.05). Average RNFL thickness in patients with iRBD is significantly thinner than in healthy controls (p < 0.05). In PD, the average RNFL thickness was dramatically thinner in the PD + pRBD group than the PD - pRBD group (p < 0.005). Compared with healthy controls, RNFL thickness was slightly thinner in the drug-naive PD group but not the PD group with drug treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). CONCLUSIONS: The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD. PMID- 27259750 TI - 2016 consensus statement of the International Ankle Consortium: prevalence, impact and long-term consequences of lateral ankle sprains. AB - The Executive Committee of the International Ankle Consortium presents this 2016 position paper with recommendations for information implementation and continued research based on the paradigm that lateral ankle sprain (LAS), and the development of chronic ankle instability (CAI), serve as a conduit to a significant global healthcare burden. We intend our recommendations to serve as a mechanism to promote efforts to improve prevention and early management of LAS. We believe this will reduce the prevalence of CAI and associated sequelae that have led to the broader public health burdens of decreased physical activity and early onset ankle joint post-traumatic osteoarthritis. Ultimately, this can contribute to healthier lifestyles and promotion of physical activity. PMID- 27259752 TI - Inflammation and the continuum model: time to acknowledge the molecular era of tendinopathy. PMID- 27259753 TI - Evidence review for the 2016 International Ankle Consortium consensus statement on the prevalence, impact and long-term consequences of lateral ankle sprains. AB - Lateral ankle sprains (LASs) are the most prevalent musculoskeletal injury in physically active populations. They also have a high prevalence in the general population and pose a substantial healthcare burden. The recurrence rates of LASs are high, leading to a large percentage of patients with LAS developing chronic ankle instability. This chronicity is associated with decreased physical activity levels and quality of life and associates with increasing rates of post-traumatic ankle osteoarthritis, all of which generate financial costs that are larger than many have realised. The literature review that follows expands this paradigm and introduces emerging areas that should be prioritised for continued research, supporting a companion position statement paper that proposes recommendations for using this summary of information, and needs for specific future research. PMID- 27259754 TI - Clinical Trial and Research Study Recruiters' Verbal Communication Behaviors. AB - The lack of accrual to research studies and clinical trials is a persistent problem with serious consequences: Advances in medical science depend on the participation of large numbers of people, including members of minority and underserved populations. The current study examines a critical determinant of accrual: the approach of patients by professional recruiters who request participation in research studies and clinical trials. Findings indicate that recruiters use a number of verbal strategies in the communication process, including translating study information (such as simplifying, using examples, and substituting specific difficult or problematic words), using linguistic reframing or metaphors, balancing discussions of research participation risks with benefits, and encouraging potential participants to ask questions. The identification of these verbal strategies can form the basis of new communication protocols that will help medical and nonmedical professionals communicate more clearly and effectively with patients and other potential participants about research studies and clinical trials, which should lead to increased accrual in the future. PMID- 27259751 TI - Return to play post-Achilles tendon rupture: a systematic review and meta analysis of rate and measures of return to play. AB - AIM: This systematic review and meta-analysis sought to identify return to play (RTP) rates following Achilles tendon rupture and evaluate what measures are used to determine RTP. DESIGN: A systematic review and meta-analysis were performed. Studies were assessed for risk of bias and grouped based on repeatability of their measure of RTP determination. DATA SOURCES: PubMed, CINAHL, Web of Science and Scopus databases were searched to identify potentially relevant articles. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies reporting RTP/sport/sport activity in acute, closed Achilles tendon rupture were included. RESULTS: 108 studies encompassing 6506 patients were included for review. 85 studies included a measure for determining RTP. The rate of RTP in all studies was 80% (95% CI 75% to 85%). Studies with measures describing determination of RTP reported lower rates than studies without metrics described, with rates being significantly different between groups (p<0.001). CONCLUSIONS: 80 per cent of patients returned to play following Achilles tendon rupture; however, the RTP rates are dependent on the quality of the method used to measure RTP. To further understand RTP after Achilles tendon rupture, a standardised, reliable and valid method is required. PMID- 27259755 TI - Elevated levels of FN1 and CCL2 in bronchoalveolar lavage fluid from sarcoidosis patients. AB - BACKGROUND: Sarcoidosis is a granulomatous systemic inflammatory disease in which more than 90 % of all patients develop pulmonary manifestations. Several gene associations have previously been described, but established and clinically useful biomarkers are still absent. This study aimed to find proteins in bronchoalveolar lavage (BAL) fluid that can be associated with the disease. METHODS: We developed and performed profiling of 94 selected proteins in BAL fluid and serum samples obtained from newly diagnosed and non-treated patients with sarcoidosis. Using multiplexed immunoassays, a total of 317 BAL and 217 serum samples were analyzed, including asthmatic patients and healthy individuals as controls. RESULTS: Our analyses revealed increased levels of eight proteins in sarcoidosis patients compared to controls. Out of these, fibronectin (FN1) and C C motif chemokine 2 (CCL2) revealed the strongest associations. In addition, cadherin 5 (CDH5) was found to correlate positively with lymphocyte cell numbers in BAL fluid. CONCLUSIONS: Applying a high throughput proteomics screening technique, we found proteins of potential clinical relevance in the context of sarcoidosis. PMID- 27259756 TI - Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome. AB - Congenital myasthenic syndromes are a group of rare and genetically heterogenous disorders resulting from defects in the structure and function of the neuromuscular junction. Patients with congenital myasthenic syndrome exhibit fatigable muscle weakness with a variety of accompanying phenotypes depending on the protein affected. A cohort of patients with a clinical diagnosis of congenital myasthenic syndrome that lacked a genetic diagnosis underwent whole exome sequencing in order to identify genetic causation. Missense biallelic mutations in the MYO9A gene, encoding an unconventional myosin, were identified in two unrelated families. Depletion of MYO9A in NSC-34 cells revealed a direct effect of MYO9A on neuronal branching and axon guidance. Morpholino-mediated knockdown of the two MYO9A orthologues in zebrafish, myo9aa/ab, demonstrated a requirement for MYO9A in the formation of the neuromuscular junction during development. The morphants displayed shortened and abnormally branched motor axons, lack of movement within the chorion and abnormal swimming in response to tactile stimulation. We therefore conclude that MYO9A deficiency may affect the presynaptic motor axon, manifesting in congenital myasthenic syndrome. These results highlight the involvement of unconventional myosins in motor axon functionality, as well as the need to look outside traditional neuromuscular junction-specific proteins for further congenital myasthenic syndrome candidate genes. PMID- 27259757 TI - A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. AB - Limb girdle muscular dystrophy type 2A is the most common limb girdle muscular dystrophy form worldwide. Although strict recessive inheritance is assumed, patients carrying a single mutation in the calpain 3 gene (CAPN3) are reported. Such findings are commonly attributed to incomplete mutation screening. In this investigation, we report 37 individuals (age range: 21-85 years, 21 females and 16 males) from 10 families in whom only one mutation in CAPN3 could be identified; a 21-bp, in-frame deletion (c.643_663del21). This mutation co segregated with evidence of muscle disease and autosomal dominant transmission in several generations. Evidence of muscle disease was indicated by muscle pain, muscle weakness and wasting, significant fat replacement of muscles on imaging, myopathic changes on muscle biopsy and loss of calpain 3 protein on western blotting. Thirty-one of 34 patients had elevated creatine kinase or myoglobin. Muscle weakness was generally milder than observed in limb girdle muscular dystrophy type 2A, but affected the same muscle groups (proximal leg, lumbar paraspinal and medial gastrocnemius muscles). In some cases, the weakness was severely disabling. The 21-bp deletion did not affect mRNA maturation. Calpain 3 expression in muscle, assessed by western blot, was below 15% of normal levels in the nine mutation carriers in whom this could be tested. Haplotype analysis in four families from three different countries suggests that the 21-bp deletion is a founder mutation. This study provides strong evidence that heterozygosity for the c.643_663del21 deletion in CAPN3 results in a dominantly inherited muscle disease. The normal expression of mutated mRNA and the severe loss of calpain 3 on western blotting, suggest a dominant negative effect with a loss-of-function mechanism affecting the calpain 3 homodimer. This renders patients deficient in calpain 3 as in limb girdle muscular dystrophy type 2A, albeit in a milder form in most cases. Based on findings in 10 families, our study indicates that a dominantly inherited pattern of calpainopathy exists, and should be considered in the diagnostic work-up and genetic counselling of patients with calpainopathy and single-allele aberrations in CAPN3. PMID- 27259758 TI - Relationship between selected perinatal paratuberculosis management interventions and passive transfer of immunity in dairy calves. AB - The objective of this cohort study was to assess the relationship between perinatal calf management practices relevant to the control of paratuberculosis and passive transfer of immunoglobulin in calves born in an endemically infected Irish dairy herd. Data from 176 calves were used to assess the effect of time spent in the calving area, individual versus non-designated calving and colostrum pasteurisation on serum total protein, zinc sulphate turbidity, globulin and gamma-glutamyltransferase. In addition, the effects of colostrum quality, volume of colostrum fed, method of colostrum administration and calving season on passive transfer were quantified. Serum samples were collected as part of routine herd health monitoring from calves aged between one and seven days. Multivariate linear and logistic regression models were used to assess the effect of each variable on the test result and failure of passive transfer as determined using a cut-off point for each diagnostic test. Colostrum pasteurisation and calving area were not significantly associated with passive transfer, whereas increased time spent in the calving pen was consistently associated with a detrimental effect. In addition, a strong seasonal effect was apparent, which appeared to be unrelated to colostrum quality and calf management. The authors are unaware of published studies documenting such a significant seasonal effect on passive transfer. PMID- 27259759 TI - [Not Available]. PMID- 27259803 TI - The default response to uncertainty and the importance of perceived safety in anxiety and stress: An evolution-theoretical perspective. AB - From a combined neurobiological and evolution-theoretical perspective, the stress response is a subcortically subserved response to uncertainty that is not 'generated' but 'default': the stress response is 'always there' but as long as safety is perceived, the stress response is under tonic prefrontal inhibition, reflected by high vagally mediated heart rate variability. Uncertainty of safety leads to disinhibiting the default stress response, even in the absence of threat. Due to the stress response's survival value, this 'erring on the side of caution' is passed to us via our genes. Thus, intolerance of uncertainty is not acquired during the life cycle, but is a given property of all living organisms, only to be alleviated in situations of which the safety is learned. When the latter is deficient, generalized unsafety ensues, which underlies chronic anxiety and stress and their somatic health risks, as well as other highly prevalent conditions carrying such risks, including loneliness, obesity, aerobic unfitness and old age. PMID- 27259804 TI - A community-based cross-sectional study for relationship of frequency of vegetables intake and osteoporosis in a Chinese postmenopausal women sample. AB - BACKGROUND: The main purpose of this study was to explore the associations between frequency of vegetables intake and osteoporosis (OP) in Chinese postmenopausal women. METHODS: We conducted a large-scale, community-based, cross sectional study to investigate the associations by using self-report questionnaire to access frequency of vegetables intake. The total of 1903 participants was available to data analysis in this study. Multiple regression models to include frequency of vegetables variable were performed to investigate the relationships for OP, after controlling for confounding factors. RESULTS: Multiple regression analysis indicated that the frequency of vegetables intake was independently and significantly associated with OP (P < 0.1 for model 1 and model 2). The postmenopausal women with high frequency of vegetables intake had a higher prevalence of OP. CONCLUSION: The findings indicated that frequency of vegetables intake was independently and significantly associated with OP. The prevalence of OP was more frequent in Chinese postmenopausal women preferring vegetables food habits. TRIAL REGISTRATION: (ClinicalTrials.gov Identifier: NCT02451397 ; date of registration: 2015-05-28). PMID- 27259806 TI - Global research trends in the medical therapy of pulmonary arterial hypertension 2000-2014. AB - BACKGROUND: Pulmonary arterial hypertension is a progressive disease of the pulmonary vasculature that affects more than 200.000 patients worldwide. Without medical treatment it leads to right heart failure and death. Extensive fundamental and clinical research has been performed throughout the globe to modify the disease and improve survival. METHODS: We performed a bibliometric study on medical treatment for pulmonary arterial hypertension to identify study characteristics, impact factors and the countries of origin of basic and clinical studies that were published between 2000 and 2014. For visualization of the obtained data density equalizing maps were prepared. RESULTS: A total of 681 studies were eligible, of these 56% were clinical studies that have included a total of 30960 patients. Most studies were performed on endothelin receptor antagonists, followed by prostacyclins and phosphodiesterase type 5 inhibitors. Impact factors did not differ between clinical and basic science studies. The United States for clinical studies, and China for basic science studies were identified as main contributors to the global scientific output. CONCLUSIONS: This first bibliometric study in the field of pulmonary arterial hypertension shows that a significant amount of scientific research was performed within the last 14 years mainly in North America, Asia and Europe. As current trends in this field of research we identified combination therapies and Asian countries being a new hatchery for emerging experimental and clinical studies. PMID- 27259805 TI - A retrospective study of two populations to test a simple rule for spirometry. AB - BACKGROUND: Chronic lung disease is common and often under-diagnosed. METHODS: To test a simple rule for conducting spirometry we reviewed spirograms from two populations, occupational medicine evaluations (OME) conducted by Saint Louis and Wake Forest Universities at 3 sites (n = 3260, mean age 64.14 years, 95 % CI 58.94-69.34, 97 % men) and conducted by Wake Forest University preop clinic (POC) at one site (n = 845, mean age 62.10 years, 95 % CI 50.46-73.74, 57 % men). This retrospective review of database information that the first author collected prospectively identified rates, types, sensitivity, specificity and positive and negative predictive value for lung function abnormalities and associated mortality rate found when conducting spirometry based on the 20/40 rule (>=20 years of smoking in those aged >= 40 years) in the OME population. To determine the reproducibility of the 20/40 rule for conducting spirometry, the rule was applied to the POC population. RESULTS: A lung function abnormality was found in 74 % of the OME population and 67 % of the POC population. Sensitivity of the rule was 85 % for an obstructive pattern and 77 % for any abnormality on spirometry. Positive and negative predictive values of the rule for a spirometric abnormality were 74 and 55 %, respectively. Patients with an obstructive pattern were at greater risk of coronary heart disease (odds ratio (OR) 1.39 [confidence interval (CI) 1.00-1.93] vs. normal) and death (hazard ratio (HR) 1.53, 95 % CI 1.20-1.84) than subjects with normal spirometry. Restricted spirometry patterns were also associated with greater risk of coronary disease (odds ratio (OR) 1.7 [CI 1.23-2.35]) and death (Hazard ratio 1.40, 95 % CI 1.08-1.72). CONCLUSIONS: Smokers (>= 20 pack years) age >= 40 years are at an increased risk for lung function abnormalities and those abnormalities are associated with greater presence of coronary heart disease and increased all-cause mortality. Use of the 20/40 rule could provide a simple method to enhance selection of candidates for spirometry evaluation in the primary care setting. PMID- 27259807 TI - The Proteasix Ontology. AB - BACKGROUND: The Proteasix Ontology (PxO) is an ontology that supports the Proteasix tool; an open-source peptide-centric tool that can be used to predict automatically and in a large-scale fashion in silico the proteases involved in the generation of proteolytic cleavage fragments (peptides) METHODS: The PxO re uses parts of the Protein Ontology, the three Gene Ontology sub-ontologies, the Chemical Entities of Biological Interest Ontology, the Sequence Ontology and bespoke extensions to the PxO in support of a series of roles: 1. To describe the known proteases and their target cleaveage sites. 2. To enable the description of proteolytic cleaveage fragments as the outputs of observed and predicted proteolysis. 3. To use knowledge about the function, species and cellular location of a protease and protein substrate to support the prioritisation of proteases in observed and predicted proteolysis. RESULTS: The PxO is designed to describe the biological underpinnings of the generation of peptides. The peptide centric PxO seeks to support the Proteasix tool by separating domain knowledge from the operational knowledge used in protease prediction by Proteasix and to support the confirmation of its analyses and results. AVAILABILITY: The Proteasix Ontology may be found at: http://bioportal.bioontology.org/ontologies/PXO . This ontology is free and open for use by everyone. PMID- 27259809 TI - MicroRNA-505 suppresses proliferation and invasion in hepatoma cells by directly targeting high-mobility group box 1. AB - AIMS: MicroRNA-505 (miR-505) expressions have been reported to be altered in the serum of HCC patients. However, the effect and underlying mechanism of miR-505 in hepatoma cells remains poorly understood. The present study intended to investigate the expression levels and the probable role and molecular basis of miR-505 in hepatoma cells. MAIN METHODS: Real-time PCR was used to determine the miR-505 expressions in hepatoma cell lines QGY-7703, SMMC-7721 and MHCC97. Furthermore, an up-or down-regulation of miR-505 was performed in MHCC97 by transfected with miR-505 mimics or anti-miR-505, respectively. Cell proliferation, cell invasion, and epithelial-mesenchymal transition were determined. Moreover, the target gene of miR-505 was also investigated. KEY FINDINGS: The expressions of miR-505 were down-regulated in three hepatoma cell lines. MHCC97 possessed the lowest miR-505 levels among the three hepatoma cell lines. Furthermore, the up-regulation of miR-505 suppressed, whereas the down regulation of miR-505 promoted proliferation, invasion and epithelial-mesenchymal transition in MHCC97. Moreover, miR-505 could directly bind to the 3' untranslated region of High-Mobility Group Box 1. Notably, High-Mobility Group Box 1 knockdown apparently promoted cell proliferation and invasion in MHCC97. SIGNIFICANCE: We investigated that MiR-505 regulates proliferation and invasion in MHCC97 cells via targeting High-Mobility Group Box 1. PMID- 27259808 TI - Indolo-pyrido-isoquinolin based alkaloid inhibits growth, invasion and migration of breast cancer cells via activation of p53-miR34a axis. AB - The tumor suppressor p53 plays a critical role in suppressing cancer growth and progression and is an attractive target for the development of new targeted therapies. We synthesized several indolo-pyrido-isoquinolin based alkaloids to activate p53 function and examined their therapeutic efficacy using NCI-60 screening. Here, we provide molecular evidence that one of these compounds, 11 methoxy-2,3,4,13-tetrahydro-1H-indolo[2',3':3,4]pyrido[1,2-b]isoquinolin-6-ylium bromide (termed P18 or NSC-768219) inhibits growth and clonogenic potential of cancer cells. P18 treatment results in downregulation of mesenchymal markers and concurrent upregulation of epithelial markers as well as inhibition of migration and invasion. Experimental epithelial-mesenchymal-transition (EMT) induced by exposure to TGFbeta/TNFalpha is also completely reversed by P18. Importantly, P18 also inhibits mammosphere-formation along with a reduction in the expression of stemness factors, Oct4, Nanog and Sox2. We show that P18 induces expression, phosphorylation and accumulation of p53 in cancer cells. P18-mediated induction of p53 leads to increased nuclear localization and elevated expression of p53 target genes. Using isogenic cancer cells differing only in p53 status, we show that p53 plays an important role in P18-mediated alteration of mesenchymal and epithelial genes, inhibition of migration and invasion of cancer cells. Furthermore, P18 increases miR-34a expression in p53-dependent manner and miR-34a is integral for P18-mediated inhibition of growth, invasion and mammosphere formation. miR-34a mimics potentiate P18 efficacy while miR-34a antagomirs antagonize P18. Collectively, these data provide evidence that P18 may represent a promising therapeutic strategy for the inhibition of growth and progression of breast cancer and p53-miR-34a axis is important for P18 function. PMID- 27259810 TI - (56)Fe ion irradiation induced apoptosis through Nrf2 pathway in mouse testis. AB - The phenomenon has raised the concerns about the safety of an extended manned mission into deep space due to the high potential for exposure to high-LET radiation during space missions. Heavy ions such as (56)Fe are main radiation sources in deep space, which could pose a significant hazard to space flight crews during and after missions. Since the testis is a radiosensitive organ, which may be susceptible to space radiation-induced changes. In this study, we investigated the effect and potential mechanisms of (56)Fe irradiation on mouse testis. Pathological characteristics were measured following whole-body irradiation with 0.5 and 1Gy (56)Fe irradiation. Flow cytometry and terminal dUTP nick end-labeling (TUNEL) were performed to detect apoptotic cells. Western blot was applied to identify potential biomarkers. Immunofluorescence was used to investigate protein localization. We found that pathologic changes and apoptosis cells were significantly higher in 1Gy group than those in 0Gy groups. In addition, protein expression and localization studies confirmed Nrf2 was involved in this acute injury. Nrf2 and its target genes HO-1 and NQO1 were up-regulated in the irradiated testis in a dose-dependent manner. Nrf2 may be useful molecular markers in radiation-induced cellular responses and is important for detecting abnormal spermatogenesis following exposure to space radiation. PMID- 27259811 TI - The effect of acute physical and mental stress on soluble cellular adhesion molecule concentration. AB - AIMS: This study investigated the impact of acute physical and mental stress on serum concentrations of vascular cell adhesion molecule (VCAM)-1 and CX3CL1/fractalkine. MATERIALS AND METHODS: Male volunteers (n=20; 21.3+/ 0.55years of age) completed a graded treadmill test to exhaustion and a 20-minute mental stress task (Stroop Color-Word Test, mental arithmetic) on separate, non consecutive days. Heart rate (HR) was measured at baseline and throughout exercise and mental stress. Blood was collected at baseline (PRE), immediately following (POST) and 30min after (POST30) exercise and mental stress. Soluble VCAM-1 and fractalkine were quantified in participant serum via enzyme-linked immunosorbent assays. KEY FINDINGS: Both treadmill exercise and the mental stress task significantly increased participant HR; although, exercise resulted in a substantially greater increase in participant HR compared to mental stress (197.82+/-11.99 vs. 38.67+/-3.10% [p<0.001]). VCAM-1 (815.74+/-139.55 vs. 738.67+/-131.59ng/mL [p=0.002]) and fractalkine (1.032+/-0.33 vs. 0.59+/ 0.20ng/mL [p<0.001]) were significantly elevated in participant serum POST maximal exercise before returning to values similar to baseline at POST30. The acute mental stress task did not significantly alter serum VCAM-1 or fractalkine at any time point. SIGNIFICANCE: In conclusion, maximal aerobic exercise results in a significant elevation of the soluble adhesion molecules VCAM-1 and fractalkine in the serum of adult males that does not occur following laboratory induced mental stress. The findings of the current investigation may suggest a novel protective role for acute aerobic exercise in vascular health via exercise induced CAM proteolysis. PMID- 27259812 TI - Overexpressed MALAT1 promotes invasion and metastasis of gastric cancer cells via increasing EGFL7 expression. AB - OBJECTIVE: Long non-coding RNAs (lncRNAs) have been demonstrated to participate in various cancers. Here, the role and its potential mechanism of MALAT1 in invasion and migration of gastric cancer (GC) were investigated. METHODS: Gastric adenocarcinoma tissues and matched normal adjacent tissues were isolated from 25 patients with GC. The expression of epidermal growth factor-like domain containing protein 7 (EGFL7) was detected in the normal gastric mucosa epithelial GES-1 cell line and three different differentiation GC cell lines, including MKN28 (well-differentiated adenocarcinoma), SGC7901 (moderately differentiated adenocarcinoma) and BGC823 (poorly differentiated adenocarcinoma). Tumor xenotransplant mouse model was established with the injection of cell line pretreated with lentiviral vectors for si-MALAT1 or si-control. RESULTS: The expression of MALAT1 was up-regulated in GC tissues and three cell lines. Si MALAT1/pcDNA-MALAT1 induced the decrease of cell invasion and migration, while the effects were reversed by the transfection of pcDNA-EGFL7/si-EGFL7. ChIP assay showed that MALAT1 regulated EGFL7 expression by altering the level of H3 histone acetylation in EGFL7 promoter. In tumor xenotransplant mice, down-regulated MALAT1 contributed to the inhibition of tumor metastasis. CONCLUSIONS: Up regulated MALAT1 promoted the invasion and metastasis of GC, and the increase of EGFL7 expression was a potential mechanism via altering its H3 histone acetylation level. PMID- 27259813 TI - Celecoxib promotes degranulation of CD8(+) T cells in HPV-induced lesions of K14 HPV16 transgenic mice. AB - AIMS: Human papillomavirus (HPV) is a known biologic carcinogen which is commonly transmitted through sexual intercourse. CD8(+) T cells are known effectors against tumour cells and an important prognostic marker in HPV-induced cancers. COX-2 inhibitors enhance CD8(+) T cell activity against some cancers. In this work, we sought to study the presence and activation of CD8(+) T lymphocytes in lesions from K14-HPV16 transgenic mice and the immunomodulatory effect of celecoxib (CXB) over these cells. MAIN METHODS: Skin samples of CXB-treated and untreated HPV16(-/-) and HPV16(+/-) mice were enzymatically digested and analysed by flow cytometry to assess CD8(+) and CD8(+)CD107a(+) T cell infiltrates. Matched skin samples were classified histologically. KEY FINDINGS: HPV16(+/-) mice presented higher CD8(+) T cell infiltration than HPV16(-/-) animals (P<0.001). Older HPV16(+/-) animals showed epidermal dysplasia and increased percentages of CD8(+)CD107a(+) T cells compared with younger animals with hyperplasia (P<0.001), validating this model for testing the effects of celecoxib on CD8(+) T cells. CXB-treated HPV16(+/-) mice showed higher percentages of CD8(+)CD107a(+) T cells compared with untreated HPV16(+/-) animals (P<0.01), but no differences were observed concerning the progression of epidermal lesions. SIGNIFICANCE: These findings indicate that celecoxib enhances the degranulation of CD8(+) T cells on HPV16-induced lesions, suggesting the potential clinical use of COX-2 inhibitors. Additionally, this study demonstrates the usefulness of the K14-HPV16 mouse model for testing therapeutic immunomodulatory approaches. PMID- 27259814 TI - Short Telomere Length and Ischemic Heart Disease: Observational and Genetic Studies in 290 022 Individuals. AB - BACKGROUND: Short telomeres are associated with aging and have been associated with a high risk of ischemic heart disease in observational studies; however, the latter association could be due to residual confounding and/or reverse causation. We wanted to test the hypothesis that short telomeres are associated with high risk of ischemic heart disease using a Mendelian randomization approach free of reverse causation and of most confounding. METHODS: We genotyped 3 genetic variants in OBFC1 (oligonucleotide/oligosaccharide binding fold containing 1), TERT (telomerase reverse transcriptase), and TERC (telomerase RNA component), which code for proteins and RNA involved in telomere maintenance. We studied 105 055 individuals from Copenhagen; 17 235 of these individuals were diagnosed with ischemic heart disease between 1977 and 2013, and 66 618 had telomere length measured. For genetic studies, we further included the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) consortium dataset, which included up to 184 967 participants and 60 837 cases of ischemic heart disease. We conducted multivariable adjusted Cox proportional hazard models for observational estimates, using logistic and instrumental variable analysis for genetic estimates. RESULTS: Observationally, a 200-bp-shorter telomere length was associated with a multivariable adjusted hazard ratio for ischemic heart disease of 1.02 (95% CI, 1.01-1.03). Per allele, telomeres were shorter by 67 bp (73-60). In meta-analyses of all 4 studies combined, odds ratios for ischemic heart disease were 1.05 (1.03-1.08) for OBCF1, 1.04 (1.02-1.06) for TERT, and 1.01 (0.99-1.03) for TERC. A genetically determined 200-bp-shorter telomere length was associated with an odds ratio for ischemic heart disease of 1.10 (1.06-1.14). CONCLUSIONS: Shorter telomeres were associated with a higher risk of ischemic heart disease, both observationally and genetically. PMID- 27259815 TI - Prostate-Specific Antigen as a Marker of Hyperandrogenism in Women and Its Implications for Antidoping. AB - BACKGROUND: Since its discovery in the 1970s, prostate-specific antigen (PSA) has become widely known as a biomarker of prostate cancer in males but has often been overlooked in female malignancies. Although the serum concentration of PSA differs between men and women by about 1000-fold, studies have suggested that PSA concentrations drastically differ among healthy females and those who exhibit increased androgen production. CONTENT: There have been reports of increased PSA expression in women exhibiting hyperandrogenic states, including polycystic ovary syndrome and hirsutism, as well as marked increases in a subset of breast cancer patients. These findings have not only revealed the remarkable diagnostic potential of PSA in a diverse range of clinical conditions but also point to its potential of becoming a useful biomarker of steroid hormone doping among female athletes. Recently, highly sensitive assays that can measure PSA at low limits of detection have been developed, which will aid in the discrimination of PSA between these different conditions. SUMMARY: The overall aim of this review is to revisit the expression of PSA in hormonally-regulated tissues and in female malignancies, and to demonstrate how the regulation of PSA permits its use in antidoping initiatives. PMID- 27259816 TI - Circulating Tumor DNA as a Cancer Biomarker: Fact or Fiction? PMID- 27259818 TI - CYP2C8-mediated interaction between repaglinide and steviol acyl glucuronide: In vitro investigations using rat and human matrices and in vivo pharmacokinetic evaluation in rats. AB - CYP2C8 is involved in the metabolic clearance of several important drugs and recent reports have shown that acyl glucuronides of gemfibrozil and clopidogrel are potent time-dependent inhibitors of CYP2C8 activity. In the present study, the inhibitory effect of steviol acyl glucuronide (SVAG), a circulating metabolite formed after the ingestion of rebaudioside A, was investigated using in vitro and in vivo systems. Results indicated that SVAG was a reversible but not a time-dependent inhibitor of CYP2C8-mediated paclitaxel 6alpha hydroxylation. SVAG was also capable of inhibiting CYP2C8-mediated repaglinide 3' hydroxylation in human liver microsomes and recombinant human CYP2C8, with Ki values of 15.8 MUM and 11.6 MUM, respectively. In contrast, SVAG did not exhibit inhibitory effect on CYP2C8 activity in rat liver microsomes. In addition, co administration of rebaudioside A with repaglinide in rats did not lead to AUC and Cmax changes of repaglinide. Although mathematic prediction using a simplified mechanistic model revealed a moderate interaction potential between repaglinide and SVAG, cautions should be given to patients with hypoglycemia if repaglinide and rebaudioside A are used in combination for the blood sugar control. PMID- 27259819 TI - Minimum standards of clinical practice for physiotherapists working in critical care settings in Australia and New Zealand: A modified Delphi technique. AB - OBJECTIVE: Achieving competency in critical care in entry-level physiotherapy courses across Australia and New Zealand is not essential, and accredited training for qualified physiotherapists working in critical care units is lacking. As a result, practice standards and training may vary. The objective was to establish consensus-based minimum clinical practice standards for physiotherapists working in critical care settings in Australia and New Zealand. DESIGN: A modified Delphi technique, which consisted of three rounds of questionnaires, was used to obtain consensus on items. SETTING: Australian and New Zealand critical care settings. PARTICIPANTS: A panel (n = 61) was invited from a pool of eligible physiotherapists throughout Australia and New Zealand (n = 93). Eligibility criteria were defined a-priori on the basis of possession of expertise and experience in the practice and teaching of critical care physiotherapy clinical skills. MAIN OUTCOME MEASURE: Questionnaires were disseminated electronically (either via email, or SurveyMonkey(r)). Items were designated by participants as being 'Essential/Unsure/Not Essential'. Consensus for inclusion was achieved when items were ranked 'Essential' by more than 70% of participants. RESULTS: Fifty physiotherapists consented and participated in the initial Delphi round, of whom 45 (90%) completed all rounds. Consensus was reached on 199 (89%) items. The panel agreed that 132 (58%) items were 'Essential' items for inclusion in the final framework. CONCLUSIONS: This is the first study to develop a consensus framework of minimum standards of practice for physiotherapists working in critical care. The clinical utility of this framework now requires assessment. PMID- 27259817 TI - Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms. AB - BACKGROUND: Growing evidence points to a key role for somatostatin (SST) in schizophrenia (SZ) and bipolar disorder (BD). In the amygdala, neurons expressing SST play an important role in the regulation of anxiety, which is often comorbid in these disorders. We tested the hypothesis that SST-immunoreactive (IR) neurons are decreased in the amygdala of subjects with SZ and BD. Evidence for circadian SST expression in the amygdala and disrupted circadian rhythms and rhythmic peaks of anxiety in BD suggest a disruption of rhythmic expression of SST in this disorder. METHODS: Amygdala sections from 12 SZ, 15 BD, and 15 control subjects were processed for immunocytochemistry for SST and neuropeptide Y, a neuropeptide partially coexpressed in SST-IR neurons. Total numbers (Nt) of IR neurons were measured. Time of death was used to test associations with circadian rhythms. RESULTS: SST-IR neurons were decreased in the lateral amygdala nucleus in BD (Nt, p = .003) and SZ (Nt, p = .02). In normal control subjects, Nt of SST-IR neurons varied according to time of death. This pattern was altered in BD subjects, characterized by decreases of SST-IR neurons selectively in subjects with time of death corresponding to the day (6:00 am to 5:59 pm). Numbers of neuropeptide Y-IR neurons were not affected. CONCLUSIONS: Decreased SST-IR neurons in the amygdala of patients with SZ and BD, interpreted here as decreased SST expression, may disrupt responses to fear and anxiety regulation in these individuals. In BD, our findings raise the possibility that morning peaks of anxiety depend on a disruption of circadian regulation of SST expression in the amygdala. PMID- 27259820 TI - Antimicrobial susceptibility of Mycoplasma bovis isolates from veal calves and dairy cattle in the Netherlands. AB - Control of Mycoplasma bovis infections depends on good husbandry practices and antibiotic treatment. To allow more prudent use of antimicrobial drugs, there is a need for information on the susceptibility profile of this pathogen. The objective of the present study was to analyse the in vitro antimicrobial susceptibility of clinical M. bovis isolates in the Netherlands. The collection comprised 95 bovine isolates, originating from lungs (n=56), mastitis milk (n=27), and synovial fluid (n=12), collected between 2008 and 2014. Minimal inhibitory concentrations (MICs) were assessed by broth microdilution, both by using in-house prepared MIC plates and by using commercially available MIC plates. For each antimicrobial agent, the range of MIC results, the MIC50, and MIC90 values were calculated. M. bovis strains recently isolated in the Netherlands appeared to be characterized by relatively high MIC values for antimicrobial agents that, until now, have been recommended by the Dutch Association of Veterinarians for treating pneumonia caused by Mycoplasma species. Fluoroquinolones appeared to be the most efficacious in inhibiting M. bovis growth, followed by tulathromycin and oxytetracycline. The highest MIC values were obtained for erythromycin, tilmicosin, and tylosin. Future studies should be done on determining M. bovis specific clinical breakpoints, standardization of methods to determine MIC values as well as molecular studies on detection of antimicrobial resistance mechanisms of M. bovis isolates to develop PCR assays for determining resistance. PMID- 27259821 TI - Colonization with methicillin-resistant Staphylococcus pseudintermedius in multi dog households: A longitudinal study using whole genome sequencing. AB - Despite a worldwide increase in the presence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs and its potential to cause serious canine health problem, the understanding of the transmission and long-term carriage of MRSP is limited. The objective of this study was to investigate the transmission of MRSP to contact dogs living in multiple dog households where one or more of the dogs had been diagnosed with a clinically apparent infection with MRSP. MRSP carriage was investigated over several months in 11 dogs living in four separate multiple dog households where an MRSP infection in a dog had been diagnosed. Whole-genome sequencing was used for genotypic characterization. Contact dogs were only MRSP-positive if the index dog was positive on the same sample occasion. Three contact dogs were consistently MRSP-negative. The data from whole genome sequencing showed similarities between isolates within each family group, indicating that MRSP was transmitted within each family. The results show that the risk of MRSP-colonization in dogs living with an MRSP infected dog is reduced if the index dog becomes MRSP negative. All of the contact dogs will not carry MRSP continuously during the time the index dog is MRSP-positive. The information yielded from whole genome sequencing showed the methodology to be a promising additional tool in epidemiologic investigations of MRSP transmission. PMID- 27259822 TI - Evolution of equine infectious anaemia in naturally infected mules with different serological reactivity patterns prior and after immune suppression. AB - Information on equine infectious anaemia (EIA) in mules, including those with an equivocal reaction in agar gel immunodiffusion test (AGIDT), is scarce. For this, a study was conducted to evaluate the clinical, viral loads and pathological findings of two groups of naturally infected asymptomatic mules, respectively with a negative/equivocal and positive AGIDT reactivity, which were subjected to pharmacological immune suppression (IS). A non-infected control was included in the study that remained negative during the observation period. Throughout the whole study, even repeated episodes of recrudescence of EIA were observed in 9 infected mules, independently from their AGIDT reactivity. These events were generally characterised by mild, transient alterations, typical of the EIA acute form represented by hyperthermia and thrombocytopenia, in concomitance with viral RNA (vRNA) peaks that were higher in the Post-IS period, reaching values similar to those of horses during the clinical acute phase of EIA. Total tissue viral nucleic acid loads were greatest in animals with the major vRNA activity and in particular in those with negative/equivocal AGIDT reactivity. vRNA replication levels were around 10-1000 times lower than those reported in horses, with the animals still presenting typical alterations of EIA reactivation. Macroscopic lesions were absent in all the infected animals while histological alterations were characterised by lymphomonocyte infiltrates and moderate hemosiderosis in the cytoplasm of macrophages. On the basis of the above results, even mules with an equivocal/negative AGIDT reaction may act as EIAV reservoirs. Moreover, such animals could escape detection due to the low AGIDT sensitivity and therefore contribute to the maintenance and spread of the infection. PMID- 27259823 TI - Lineage associated expression of virulence traits in bovine-adapted Staphylococcus aureus. AB - Bovine mastitis is the most costly disease to the dairy industry worldwide with Staphylococcus aureus commonly associated with intramammary infections that are persistent and refractory to treatment. The strains of S. aureus that cause mastitis predominantly belong to a number of well-described bovine-adapted lineages. The objective of this study was to determine if a variety of potential virulence traits were associated with lineage. Bovine-adapted S. aureus isolates (n=120), belonging to lineages CC97, CC151 and ST136, were tested for their ability to adhere to and internalise within cultured bovine mammary epithelial cells (bMEC), to bind bovine fibronectin, to form a biofilm in TSB, TSB+1% glucose and TSB+4% NaCl, and to induce an immune response from bMEC. There were no significant differences between the lineages in ability to adhere to or internalise within bMEC although there were significant differences between individual isolates. For lineages CC97 and ST136, mammalian cell adherence was correlated with the ability to bind bovine fibronectin, however isolates from CC151 could not bind bovine fibronectin in vitro, but adhered to bMEC in a fibronectin-independent manner. There were significant differences between the lineages in ability to form a biofilm in all three growth media with ST136 forming the strongest biofilm while CC151 formed the weakest biofilm. Lineages also differed in their ability to elicit an immune response from bMEC with CC97 eliciting a stronger immune response than CC151 and ST136. These data indicate the potential for both lineage and strain-specific virulence and a strain specific response to infection in vivo and caution against extrapolating an effect from a single strain of S. aureus to draw conclusions regarding virulence or the host response to infection in unrelated lineages. PMID- 27259824 TI - The first experimental research on the pathogenicity of Arcobacter butzleri in zebrafish. AB - This experimental study was conducted to investigate the pathogenicity and histopathology of Arcobacter butzleri in zebrafish model organism. Firstly, mean infective dose (ID50) of A. butzleri was calculated in zebrafish as 1.3*10(8)CFU/mL and 1*10(5)CFU/mL by immersion and intraperitoneal injection, respectively. For histopathological trials, the ID50 of A. butzleri were given to zebrafish by both immersion and intraperitoneal routes and then, clinical and pathological findings were evaluated on days 1, 3, 5, 7 and 21 of the experiment. During the experimental period, no clinical signs or gross lesions of disease were observed in the zebrafish groups infected with the ID50 of A. butzleri by either method. In the histopathological examination, acute inflammation characterized by neutrophil and plasma cells and local necrosis or congestion were determined in liver, kidney, spleen, gaster and other visceral organs. In addition peritonitis, leukocyte infiltration, villous atrophy and septicemia were observed in the experimental groups. Neither gross nor microscopic lesions were detected in the control groups. This study presented the first report of experimental A. butzleri infection in wild zebrafish. In the light of the findings obtained here, it was concluded that zebrafish could be used as a model organism to investigate pathogenicity and histopathology of arcobacters. PMID- 27259825 TI - Aerosol transmission of foot-and-mouth disease virus Asia-1 under experimental conditions. AB - Foot-and-mouth disease virus (FMDV) control measures rely on understanding of virus transmission mechanisms. Direct contact between naive and infected animals or spread by contaminated fomites is prevented by quarantines and rigorous decontamination procedures during outbreaks. Transmission of FMDV by aerosol may not be prevented by these control measures and this route of transmission may allow infection of animals at distance from the infection source. Understanding the potential for aerosol spread of specific FMDV strains is important for informing control strategies in an outbreak. Here, the potential for transmission of an FMDV Asia 1 strain between pigs and cattle by indirect aerosol exposure was evaluated in an experimental setting. Four naive calves were exposed to aerosols emitted from three infected pigs in an adjacent room for a 10h period. Direct contact between pigs and cattle and fomite transfer between rooms was prevented. Viral titres in aerosols emitted by the infected pigs were measured to estimate the dose that calves were exposed to. One of the calves developed clinical signs of FMD, whilst there was serological evidence for spread to cattle by aerosol transmission in the remaining three calves. This highlights the possibility that this FMDV Asia 1 strain could be spread by aerosol transmission given appropriate environmental conditions should an outbreak occur in pigs. Our estimates suggest the exposure dose required for aerosol transmission was higher than has been previously quantified for other serotypes, implying that aerosols are less likely to play a significant role in transmission and spread of this FMDV strain. PMID- 27259826 TI - Determining the optimal number of individual samples to pool for quantification of average herd levels of antimicrobial resistance genes in Danish pig herds using high-throughput qPCR. AB - The primary objective of this study was to determine the minimum number of individual fecal samples to pool together in order to obtain a representative sample for herd level quantification of antimicrobial resistance (AMR) genes in a Danish pig herd, using a novel high-throughput qPCR assay. The secondary objective was to assess the agreement between different methods of sample pooling. Quantification of AMR was achieved using a high-throughput qPCR method to quantify the levels of seven AMR genes (ermB, ermF, sulI, sulII, tet(M), tet(O) and tet(W)). A large variation in the levels of AMR genes was found between individual samples. As the number of samples in a pool increased, a decrease in sample variation was observed. It was concluded that the optimal pooling size is five samples, as an almost steady state in the variation was observed when pooling this number of samples. Good agreement between different pooling methods was found and the least time-consuming method of pooling, by transferring feces from each individual sample to a tube using a 10MUl inoculation loop and adding 3.5ml of PBS, approximating a 10% solution, can therefore be used in future studies. PMID- 27259827 TI - Genome-wide mining of potential virulence-associated genes in Riemerella anatipestifer using random transposon mutagenesis. AB - Riemerella anatipestifer infection is a severe disease confronting the duck industry worldwide. However, little is known about the molecular basis of R. anatipestifer pathogenesis. In this study, we screened 3580 transposon Tn4351 insertion mutagenesis mutants of the highly virulent strain YZb1 in a duckling infection experiment and found 29 of them to be attenuated and 28 potential virulence-associated genes were identified. Molecular characterization of transposon insertion sites showed that of the 28 screened genes, two were predicted to encode TonB-dependent outer membrane receptor (plugs), sixteen encoded enzymes, and seven encoded hypothetical proteins. In addition, of the 28 affected genes, 19 were only found in bacteria belonging to the phylum Bacteroidetes and 10 were only found in the family Flavobacteriaceae. The median lethal dose of the mutants M11 and M29, which was affected in Riean_0060 and Riean_1537 respectively, were about 1700-fold and 210-fold higher than that of the wild-type strain YZb1, and those of the complemented strains M11(pRES Riean_0060) and M29(pRES-Riean_1537) were decreased by 25- and 3-fold respectively compared to those of the mutants M11 and M29. Additional analysis indicated that the blood bacterial loading of ducklings infected with M11 or M29 was decreased significantly, as compared with that in ducklings infected with the wild-type strain YZb1. Thus, our results indicate that Riean_0060 and Riean_1537 were involved in R. anatipestifer pathogenesis. PMID- 27259828 TI - Low pathogenic avian influenza (H9N2) in chicken: Evaluation of an ancestral H9 MVA vaccine. AB - Modified Vaccinia Ankara (MVA) has proven its efficacy as a recombinant vector vaccine for numerous pathogens including influenza virus. The present study aimed at evaluating a recombinant MVA candidate vaccine against low pathogenic avian influenza virus subtype H9N2 in the chicken model. As the high genetic and antigenic diversity of H9N2 viruses increases vaccine design complexity, one strategy to widen the range of vaccine coverage is to use an ancestor sequence. We therefore generated a recombinant MVA encoding for the gene sequence of an ancestral hemagglutinin H9 protein (a computationally derived amino acid sequence of the node of the H9N2 G1 lineage strains was obtained using the ANCESCON program). We analyzed the genetics and the growth properties of the MVA vector virus confirming suitability for use under biosafety level 1 and tested its efficacy when applied either as an intra-muscular (IM) or an oral vaccine in specific pathogen free chickens challenged with A/chicken/Tunisia/12/2010(H9N2). Two control groups were studied in parallel (unvaccinated and inoculated birds; unvaccinated and non-inoculated birds). IM vaccinated birds seroconverted as early as four days post vaccination and neutralizing antibodies were detected against A/chicken/Tunisia/12/2010(H9N2) in all the birds before challenge. The role of local mucosal immunity is unclear here as no antibodies were detected in eye drop or aerosol vaccinated birds. Clinical signs were not detected in any of the infected birds even in absence of vaccination. Virus replication was observed in both vaccinated and unvaccinated chickens, suggesting the MVA-ancestral H9 vaccine may not stop virus spread in the field. However vaccinated birds showed less histological damage, fewer influenza-positive cells and shorter virus shedding than their unvaccinated counterparts. PMID- 27259829 TI - The serine protease autotransporter Tsh contributes to the virulence of Edwardsiella tarda. AB - The temperature-sensitive hemagglutinin (Tsh), identified as serine protease autotransporters of the Enterobacteriaceae (SPATEs) proteins, is an important virulence factor for avian-pathogenic Escherichia coli (APEC) and uropathogenic E. coli. However, little is known about the role of Tsh as a virulence factor in Edwardsiella tarda, a severe fish pathogen. In this study, we characterized the Tsh of E. tarda (named TshEt) and examined its function and vaccine potential. TshEt is composed of 1224 residues and has three functional domains typical for autotransporters. Quantitative real-time reverse transcriptase-PCR analysis showed that expression of tshEt was upregulated under conditions of high temperature, increased cell density, high pH, and iron starvation and during the infection of host cells. A markerless tsh in-frame mutant strain, TX01Deltatsh, was constructed to determine whether TshEt participates in the pathogenicity of E. tarda, Compared to the wild type TX01, TX01Deltatsh exhibited (i) retarded biofilm growth, (ii) decreased resistance against serum killing, (iii) impaired ability to block the host immune response, (iv) attenuated tissue and cellular infectivity. Introduction of a trans-expressed tsh gene restored the lost virulence of TX01Deltatsh. The passenger domain of TshEt contains a putative serine protease (PepS) that exhibits apparent proteolytic activity when expressed in and purified from E. coli as a recombinant protein (rPepS). When used as a subunit vaccine to immunize Japanese flounder, rPepS was able to induce effective immune protection. This is the first study of Tsh in a fish pathogen, and the results suggest that TshEt exerts pleiotropic effects on the pathogenesis of E. tarda. PMID- 27259830 TI - The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus infection suppresses Th17 cells response in vivo. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to immunomodulate innate and adaptive immunity of pigs. The Chinese highly pathogenic PRRSV (HP-PRRSV) infection causes severe bacterial secondary infection in pigs. However, the mechanism in relation to the bacterial secondary infection induced by HP-PRRSV remains unknown. In the present study, Th17 cells response in peripheral blood, lungs, spleens and lymph nodes of piglets were analyzed, and bacterial loads in lungs of piglets were examined upon HP-PRRSV infection. Meanwhile the changes of CD4(+) and CD8(+) T cells in peripheral blood of the inoculated piglets were analyzed. The results showed that HP-PRRSV-inoculated piglets exhibited a suppressed Th17 cells response in peripheral blood and a reduced number of Th17 cells in lungs, and higher bacterial loads in lungs, compared with low pathogenic PRRSV. Moreover, HP-PRRSV obviously resulted in severe depletion of porcine T cells in peripheral blood at the early stage of infection. These findings indicate that HP-PRRSV infection suppresses the response of Th17 cells that play an important role in combating bacterial infections, suggesting a possible correlation between the suppression of Th17 cells response in vivo and bacterial secondary infection induced by HP-PRRSV. Our present study adds a novel insight into better understanding of the pathogenesis of the Chinese HP-PRRSV. PMID- 27259832 TI - Genetic analysis of a Treponema phagedenis locus encoding antigenic lipoproteins with potential for antigenic variation. AB - Digital dermatitis (DD) is a painful and debilitating claw disease in cattle. Spirochetes of the genus Treponema are found in high numbers in the lesions and are likely to be involved in the pathogenesis. The occurrence of Treponema phagedenis in DD lesions, especially near the interface of healthy and diseased tissue, suggests that this species contributes to the development and/or progression of the lesions. In this study we characterized a genetic locus in T. phagedenis that contains coding regions for three antigenic proteins, PrrA, VpsA, and VpsB. Comparative analysis of homologous loci from fifteen strains suggests that prrA may be transposed into or out of this locus. Alterations in the copy number of TA repeats within the putative promoter region may regulate VpsA/B expression. The vpsA and prrA genes occur in allelic variants in different T. phagedenis isolates and may provide one explanation for the antigenic variation observed in T. phagedenis DD isolates. PMID- 27259831 TI - National reduction in porcine circovirus type 2 prevalence following introduction of vaccination. AB - Porcine circovirus type 2 (PCV2), a small, single-stranded circular DNA virus and the causative agent of porcine circovirus associated disease (PCVAD), was first observed in the mid-1990s in pigs with a post-weaning wasting disease. In 2006 the number of PCVAD cases greatly increased, marking it as an important viral pathogen for the United States (US) swine industry. PCV2 vaccines were introduced to the US in 2006 in response to widespread outbreaks of PCVAD. These vaccines were effective in preventing disease, but did not eliminate virus from the animals. In 2006, prior to vaccine use, a study of PCV2 prevalence in pig herds across the US was performed in conjunction with the US National Animal Health Monitoring System. In 2012, 6 years after widespread PCV2 vaccination, this study was repeated. Since the introduction of PCV2 vaccines in 2006, viral presence and viral loads have greatly decreased, and a genotypic shift dominated by PCV2b has occurred. Antibody levels have decreased in the pig population, but approximately 95% of sites continue to be antibody-positive. Widespread vaccination has controlled PCVAD and decreased PCV2 prevalence to the point that viremia is not detected on many sites. Thus, continued vaccination may lead to PCV2 elimination in the national herd over time. PMID- 27259833 TI - Characterization and functional analysis of toll-like receptor 4 in Chinese soft shelled turtle Pelodiscus sinensis. AB - Mammalian Toll-like receptor 4 (TLR4) recognizes lipopolysaccharide (LPS) in initiating the innate immune responses. Early studies indicate that turtles are more resistant to LPS challenge than mammals. It remains unknown if turtles express TLR4 and why they are more resistant to LPS. In this study, TLR4 gene from Chinese soft-shelled turtle, Pelodiscus sinensis, was cloned and characterized. The full length cDNA of turtle TLR4 (tTLR4) consists of 3396 base pairs with an 2499-bp open reading frame, encoding 833 amino acids. Phylogenetic and syntenic analyses suggest that tTLR4 is to be orthologous to human TLR4. Its mRNA expression was up-regulated in spleen and blood of turtles upon Aeromonas hydrophila infection. Stimulation of turtle peripheral blood monocytes with LPS significantly upregulated tTLR4 mRNA and inflammation-related gene expression, such as Interleukin-1beta (IL-1beta) and cyclooxygenase-2 (COX-2). In tTLR4 expressing HEK293 cells, higher concentration of LPS exposure could enhance the activity of the NF-kappaB promoter, but not the INF-beta promoter. Such activity required co-expression of turtle myeloid differentiation factor 2 (tMD2) and cluster of differentiation 14 (tCD14). These results provide evidence for a functional TLR4 in reptiles and, together with the syntenic analysis, support the idea that the TLR4 receptor for LPS recognition may have arisen after reptiles. PMID- 27259834 TI - Manganese ion concentration affects production of human core 3 O-glycan in Saccharomyces cerevisiae. AB - BACKGROUND: Production of various mucin-like glycoproteins could be useful for development of antibodies specific to disease-related glycoproteins as well as for the biosynthesis of clinically useful glycoproteins. A Saccharomyces cerevisiae strain capable of in vivo production of mucin-type core 1 structure (Galbeta1-3GalNAcalpha1-O-Ser/Thr) has been reported, but a strain producing core 3 structure (GlcNAcbeta1-3GalNAcalpha1-O-Ser/Thr) has not been constructed. METHODS: To generate core 3-producing strain, genes encoding uridine diphosphate (UDP)-Gal-4-epimerase, UDP-GalNAc transporter, UDP-GlcNAc transporter, and two glycosyltransferases were integrated into the genome. A Mucin-1-derived acceptor peptide (MUC1ap) was expressed as an acceptor. The amount of the resulting modified peptide was analyzed by HPLC. RESULTS: Introduction of a codon-optimized UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 (beta3Gn-T6) gene yielded increases in beta3Gn-T6 activity but did not alter the level of core 3 production. The highest in vitro activity of beta3Gn-T6 was observed at Mn(2+) concentrations of 10mM and above. Supplementation of MnCl2 to the culture medium yielded increases of up to 25% in the accumulation of core 3 on the MUC1ap. The yeast invertase from the core 3-producing strain was less extensively N glycosylated; however, it was partially restored by the addition of MnCl2 to the medium. CONCLUSIONS: Physiological Mn(2+) concentration in S. cerevisiae was insufficient to facilitate optimal synthesis of core 3. Mn(2+) supplementation led to up-regulation of reaction of glycosylation in the Golgi, resulting in increases of core 3 production. GENERAL SIGNIFICANCE: This study reveals that control of Mn(2+) concentration is important for production of specific mammalian type glycans in S. cerevisiae. PMID- 27259835 TI - Pulmonary and pleural inflammation after intratracheal instillation of short single-walled and multi-walled carbon nanotubes. AB - Relationships between the physical properties of carbon nanotubes (CNTs) and their toxicities have been studied. However, little research has been conducted to investigate the pulmonary and pleural inflammation caused by short-fiber single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). This study was performed to characterize differences in rat pulmonary and pleural inflammation caused by intratracheal instillation with doses of 0.15 or 1.5mg/kg of either short-sized SWCNTs or MWCNTs. Data from bronchoalveolar lavage fluid analysis, histopathological findings, and transcriptional profiling of rat lungs obtained over a 90-day period indicated that short SWCNTs caused persistent pulmonary inflammation. In addition, the short MWCNTs markedly impacted alveoli immediately after instillation, with the levels of pulmonary inflammation following MWCNT instillation being reduced in a time-dependent manner. MWCNT instillation induced greater levels of pleural inflammation than did short SWCNTs. SWCNTs and MWCNTs translocated in mediastinal lymph nodes were observed, suggesting that SWCNTs and MWCNTs underwent lymphatic drainage to the mediastinal lymph nodes after pleural penetration. Our results suggest that short SWCNTs and MWCNTs induced pulmonary and pleural inflammation and that they might be transported throughout the body after intratracheal instillation. The extent of changes in inflammation differed following SWCNT and MWCNT instillation in a time-dependent manner. PMID- 27259836 TI - [Traffic accidentability and risky driving behavior in young people in New Caledonia. Results of study Situation Sociale et Comportements de Sante des Jeunes en Nouvelle-Caledonie]. AB - BACKGROUND: New Caledonia has one of the highest global rates of death from road accidents: 240 deaths per million inhabitants in 2011 with a majority of young people. However, research on driving behaviors has remained rare. METHODS: A cross-sectional survey based on face-to-face questionnaire with 1400 male and female youth aged 16 to 25 was conducted in 2007. It was used to measure the frequency of accidents and to compute a score of driving behaviors and their associations with socio-demographic characteristics, lifestyles as well as other health behaviors. RESULTS - CONCLUSION: A total of 10.6% of boys and 6.5% of girls reported a car accident in the previous twelve months period. Among male participants risky driving behavior was associated with having a degree (ORa=2, 95% CI [1.1-3.8]), sport practices (ORa=3.7, 95% CI [1.9-7.05]), involvement in a fight in the last twelve months (ORa=2.2, 95% CI [1.4-3.4]) and precocity of cannabis use (ORa=1.8, 95% CI [1.2-2.8]). Youth living in couple and those with children presented with higher risk-taking scores. Among female participants, young age at cannabis initiation (ORa=3.1, 95% CI [1.5-6.4]) and at sexual debut (ORa=2.4, 95% CI [1.1-5.1]) were associated with driving risk-taking. Finally, younger age at first alcohol intoxication was associated with risky behavior on the road in both sexes. These results highlighted the multidimensional nature of risk-taking behaviors on the road and showed that they are part of, for boys and girls, a larger pattern of risky behaviors. Such results suggest to include behaviors on the road in a comprehensive approach of prevention. PMID- 27259838 TI - Relationship between prefrontal hemodynamic responses and quality of life differs between melancholia and non-melancholic depression. AB - This study aimed to determine whether quality of life (QOL) reflects specific functional abnormalities of frontotemporal hemodynamic responses in melancholia. We recruited 30 patients with major depressive disorder (MDD) with melancholic features (MDD-MF), 52 with non-melancholic features (MDD-NMF), and 68 healthy control subjects who were matched for age, sex ratio, and years of education. QOL was assessed using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36), and regional hemodynamic responses during a verbal fluency task were monitored with near-infrared spectroscopy (NIRS). Patients with MDD-MF scored significantly lower than those with MDD-NMF on the role emotional domain of SF 36. Both MDD patient groups exhibited lower hemodynamic responses in the frontotemporal regions than the control group. Hemodynamic responses in the frontotemporal regions were significantly smaller in patients with MDD-MF than in those with MDD-NMF. The role emotional domain of patients with MDD-MF was significantly and positively correlated with hemodynamic responses in the prefrontal region, whereas that of patients with MDD-NMF revealed no significant correlation. In conclusion, our results indicate that patients with MDD-MF exhibit qualitatively distinct prefrontal dysfunction patterns associated with emotional role functioning compared with patients with MDD-NMF. PMID- 27259839 TI - Reflectance confocal microscopy in the diagnosis of vesicobullous disorders: case series with pathologic and cytologic correlation and literature review. AB - BACKGROUND: Vesicobullous disorders are characterized by intraepidermal or subepidermal blistering resulting from different pathogenetic mechanisms. The diagnosis is generally based on clinical examination and semi-invasive/invasive procedures such as cytology and histopathology. In vivo reflectance confocal microscopy (RCM) is a non-invasive technique for real-time, en face imaging of the epidermis and upper dermis with high resolution close to conventional histopathology. PURPOSE: To evaluate RCM features of different vesicobullous diseases and correlate with cytologic and histopathologic examination. METHODS: Ten patients (6M/4F, age range: 9-81 years) affected by blistering diseases, such as herpes simplex, herpes zoster, Kaposi's varicelliform eruption, pemphigus vulgaris, Hailey-Hailey disease, bullous pemphigoid, and porphyria cutanea tarda were evaluated using a handheld RCM device. RESULTS: In our study, a clear correlation between RCM and Tzanck's test and/or histopathology was observed. RCM allowed in all cases an easy identification of the blister spaces and of the split levels, and in some cases specific features were detected, such as giant keratinocytes in herpes infections and acantholytic cells in pemphigus vulgaris and Hailey-Hailey disease. CONCLUSION: Reflectance confocal microscopy may support the clinical diagnosis of vesicobullous disorders and indicate to the physician the appropriate patient management and/or the need for further investigation. PMID- 27259840 TI - Antimicrobial and immunomodulatory effects of tedizolid against methicillin resistant Staphylococcus aureus in a murine model of hematogenous pulmonary infection. AB - Tedizolid (TZD) is a second-generation oxazolidinone and demonstrates potent in vitro activity against multidrug-resistant Gram-positive bacteria. Phase III studies in patients with acute bacterial skin and skin structure infections (ABSSSI) have demonstrated the non-inferiority of TZD to linezolid (LZD). However, there are only a few studies that show the effect of TZD in pulmonary infections. In this study, we investigated the effect of TZD in a murine model of hematogenous pulmonary infection caused by methicillin-resistant Staphylococcus aureus (MRSA). The mice were treated either twice daily with saline (control), 25mg/kg of vancomycin (low-VAN), 110mg/kg of vancomycin (high-VAN), 120mg/kg of LZD or once daily with 20mg/kg of TZD. As compared to the control, the low- and high-VAN treatment groups, LZD and TZD significantly improved the survival rate, reduced the bacterial count in the lungs. Furthermore, TZD decreased the area of central bacterial colony zone (CBCZ) at 36h post-inoculation, compared with the control. In addition, we investigated the immunomodulatory effect of TZD by evaluating the plasma concentrations of the inflammatory cytokines. Although there were no significant differences in the bacterial count in the lungs amongst the drugs at 26h post-inoculation, TZD and LZD significantly improved the plasma concentrations of TNF-alpha, IL-6 and MIP-2, in comparison with the control. In this study, both TZD and LZD demonstrated antimicrobial and immunomodulatory efficacy in a murine model of hematogenous pulmonary infection caused by MRSA. PMID- 27259853 TI - The Human Thymus Is Enriched for Autoreactive B Cells. AB - The human thymus has been shown to host B cells, which have been implicated in presentation of autoantigens for negative selection of T cell progenitors. Although these Ags are thought to be taken up through their surface Igs, data on thymic Ig gene repertoires are limited and reactivity to autoantigens has not been demonstrated. We therefore studied the Ig gene repertoires and reactivity to autoantigens of single-sorted B cells from pediatric thymus, and compared these with mature B cells from fetal and pediatric bone marrow. Nearly all B cells in thymus were mature and displayed an Ig gene repertoire that was similar to pediatric bone marrow. Fetal mature B cells predominantly used proximal V, D, and J genes, and their Abs were highly reactive to dsDNA. In contrast, thymic B cells were enriched for autoreactive clones that showed increased specificity to peptide autoantigens. Thus, most B cells in the thymus are resident rather than developing, and are enriched for autoantigen binding. These features support current models for a role of thymic B cells in presentation of autoantigens to developing T cells during negative selection. PMID- 27259854 TI - Low-Dose IL-2 Induces Regulatory T Cell-Mediated Control of Experimental Food Allergy. AB - Regulatory T cells (Tregs) are pivotal for maintenance of immune self-tolerance and also regulate immune responses to exogenous Ags, including allergens. Both decreased Treg number and function have been reported in allergic patients, offering new therapeutic perspectives. We previously demonstrated that Tregs can be selectively expanded and activated by low doses of IL-2 (ld-IL-2) inducing immunoregulation without immunosuppression and established its protective effect in autoimmune diseases. In this study, we evaluated the ability of ld-IL-2 to control allergy in an experimental model of food allergy. Ld-IL-2 induced Treg expansion and activation that elicited protection against clinical manifestations of food allergy in two mouse models with OVA and peanut. This clinical effect was lost in Treg-depleted mice, demonstrating the major contribution of Tregs in ld IL-2 efficacy. Mechanistic studies further indicated that protection from allergy could be explained by a Treg-dependent local modification of the Th1/Th2 balance and an inhibition of mast cell recruitment and activation. Preventive and therapeutic effects of ld-IL-2 were observed over a 7-mo-period, highlighting its long-term efficacy. This study demonstrated that ld-IL-2 is efficient to prevent and to treat allergic immune responses, and thus represents a promising therapeutic strategy for managing allergic diseases. PMID- 27259855 TI - IL-27 Induced by Select Candida spp. via TLR7/NOD2 Signaling and IFN-beta Production Inhibits Fungal Clearance. AB - Candida spp. elicit cytokine production downstream of various pathogen recognition receptors, including C-type lectin-like receptors, TLRs, and nucleotide oligomerization domain (NOD)-like receptors. IL-12 family members IL 12p70 and IL-23 are important for host immunity against Candida spp. In this article, we show that IL-27, another IL-12 family member, is produced by myeloid cells in response to selected Candida spp. We demonstrate a novel mechanism for Candida parapsilosis-mediated induction of IL-27 in a TLR7-, MyD88-, and NOD2 dependent manner. Our data revealed that IFN-beta is induced by C. parapsilosis, which in turn signals through the IFN-alpha/beta receptor and STAT1/2 to induce IL-27. Moreover, IL-27R (WSX-1)-deficient mice systemically infected with C. parapsilosis displayed enhanced pathogen clearance compared with wild-type mice. This was associated with increased levels of proinflammatory cytokines in the serum and increased IFN-gamma and IL-17 responses in the spleens of IL-27R deficient mice. Thus, our data define a novel link between C. parapsilosis, TLR7, NOD2, IFN-beta, and IL-27, and we have identified an important role for IL-27 in the immune response against C. parapsilosis Overall, these findings demonstrate an important mechanism for the suppression of protective immune responses during infection with C. parapsilosis, which has potential relevance for infections with other fungal pathogens. PMID- 27259856 TI - Regulatory T Cells Control Th2-Dominant Murine Autoimmune Gastritis. AB - Pernicious anemia and gastric carcinoma are serious sequelae of autoimmune gastritis (AIG). Our study indicates that in adult C57BL/6-DEREG mice expressing a transgenic diphtheria toxin receptor under the Foxp3 promoter, transient regulatory T cell (Treg) depletion results in long-lasting AIG associated with both H(+)K(+)ATPase and intrinsic factor autoantibody responses. Although functional Tregs emerge over time during AIG occurrence, the effector T cells rapidly become less susceptible to Treg-mediated suppression. Whereas previous studies have implicated dysregulated Th1 cell responses in AIG pathogenesis, eosinophils have been detected in gastric biopsy specimens from patients with AIG. Indeed, AIG in DEREG mice is associated with strong Th2 cell responses, including dominant IgG1 autoantibodies, elevated serum IgE, increased Th2 cytokine production, and eosinophil infiltration in the stomach-draining lymph nodes. In addition, the stomachs exhibit severe mucosal and muscular hypertrophy, parietal cell loss, mucinous epithelial cell metaplasia, and massive eosinophilic inflammation. Notably, the Th2 responses and gastritis severity are significantly ameliorated in IL-4- or eosinophil-deficient mice. Furthermore, expansion of both Th2-promoting IFN regulatory factor 4(+) programmed death ligand 2(+) dendritic cells and ILT3(+) rebounded Tregs was detected after transient Treg depletion. Collectively, these data suggest that Tregs maintain physiological tolerance to clinically relevant gastric autoantigens, and Th2 responses can be a pathogenic mechanism in AIG. PMID- 27259858 TI - MMP-25 Metalloprotease Regulates Innate Immune Response through NF-kappaB Signaling. AB - Matrix metalloproteases (MMPs) regulate innate immunity acting over proinflammatory cytokines, chemokines, and other immune-related proteins. MMP-25 (membrane-type 6-MMP) is a membrane-bound enzyme predominantly expressed in leukocytes whose biological function has remained largely unknown. We have generated Mmp25-deficient mice to elucidate the in vivo function of this protease. These mutant mice are viable and fertile and do not show any spontaneous phenotype. However, Mmp25-null mice exhibit a defective innate immune response characterized by low sensitivity to bacterial LPS, hypergammaglobulinemia, and reduced secretion of proinflammatory molecules. Moreover, these immune defects can be tracked to a defective NF-kappaB activation observed in Mmp25-deficient leukocytes. Globally, our findings provide new mechanistic insights into innate immunity through the activity of MMP-25, suggesting that this proteinase could be a potential therapeutic target for immune-related diseases. PMID- 27259857 TI - Multiple Inhibitory Pathways Contribute to Lung CD8+ T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection. AB - Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4. Moreover, coexpression of these receptors continued to increase even after viral clearance, with most virus-specific lung TCD8 expressing three or more inhibitory receptors on day 14 postinfection. Viral infection also increased expression of inhibitory ligands by both airway epithelial cells and APCs, further establishing an inhibitory environment. In vitro Ab blockade revealed that multiple inhibitory receptors contribute to TCD8 impairment induced by either human metapneumovirus or influenza virus infection. In vivo blockade of T cell Ig mucin 3 signaling failed to enhance TCD8 function or reduce viral titers. However, blockade of LAG-3 in PD-1-deficient mice restored TCD8 effector functions but increased lung pathology, indicating that LAG-3 mediates lung TCD8 impairment in vivo and contributes to protection from immunopathology during viral clearance. These results demonstrate that an orchestrated network of pathways modifies lung TCD8 functionality during viral LRI, with PD-1 and LAG-3 serving prominent roles. Lung TCD8 impairment may prevent immunopathology but also contributes to recurrent lung infections. PMID- 27259859 TI - Outlet strut fracture and leaflet escape of Bjork-Shiley convexo-concave valve. AB - Prosthetic valve fracture is a serious complication and may arise in patient post valve replacement. We experienced an outlet strut fracture and leaflet escape of a Bjork-Shiley convexo-concave valve. We performed an emergency redo mitral valve replacement and successfully retrieved the fractured strut and escaped leaflet from superficial femoral artery and the abdominal aorta. The patient showed an uneventful postoperative recovery. PMID- 27259860 TI - Aquimarina aggregata sp. nov., isolated from seawater. AB - A novel Gram-stain-negative, agarolytic, rod-shaped, non-flagellated, strictly aerobic strain with gliding motility, designated RZW4-3-2T, was isolated from coastal seawater of the Yellow Sea in China (119.625 degrees E 35.517 degrees N). The organism grew optimally at 28 degrees C, at pH 7.0 and in the presence of 2.0-3.0 % (w/v) NaCl. The strain required seawater or artificial seawater for growth, and NaCl alone did not support growth. Strain RZW4-3-2T contained MK-6 as the major respiratory quinone and iso-C17 : 0 3-OH, iso-C15 : 0, iso-C15 : 1 G and iso-C15 : 0 3-OH as the dominant fatty acids. The polar lipids of strain RZW4 3-2T comprised phosphatidylethanolamine, five unknown phospholipids and one unknown lipid. The DNA G+C content of strain RZW4-3-2T was 32.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain was related most closely to Aquimarina pacifica SW150T, Aquimarina macrocephali JCM 15542T and Aquimarina muelleri LMG 22569T with 98.1, 97.4 and 97.1 % sequence similarities, respectively. The estimated DNA-DNA hybridization values were 20.00+/-2.31 %, 20.70+/-2.33 % and 20.70+/-2.32 % between strain RZW4 3-2T and A. pacifica SW150T, A. macrocephali JCM 15542T and A. muelleri LMG 22569T, respectively. On the basis of results of polyphasic analyses, strain RZW4 3-2T represents a novel species of the genus Aquimarina, for which the name Aquimarinaaggregata sp. nov. is proposed. The type strain is RZW4-3-2T (=JCM 30824T=MCCC 1K00698T). PMID- 27259861 TI - Immunotherapy for Lung Cancer. AB - Immune evasion is recognized as a key strategy for cancer survival and progression. Hence, various approaches to restore antitumor immune responses are currently being investigated. In particular, agents targeting immune checkpoints, such as the cytotoxic T-lymphocyte-associated antigen-4 receptor and programmed death-1 receptor, have shown potential for improving tumor responses and survival in lung cancer patients. With the first immunomodulating agents having been approved for treatment of selected lung cancer patients, there are high expectations that treatment outcomes may be improved with the incorporation of immunotherapies into the various treatment cascades. PMID- 27259862 TI - Cardiovascular magnetic resonance of mitral valve length in hypertrophic cardiomyopathy. AB - BACKGROUND: Previous data suggest that mitral valve leaflets are elongated in hypertrophic cardiomyopathy (HCM), and mitral valve leaflet elongation may constitute a primary phenotypic expression of HCM. Our objective was to measure the length of mitral valve leaflets by cardiovascular magnetic resonance (CMR) in subjects with HCM caused by a Finnish founder mutation in the myosin-binding protein C gene (MYBPC3-Q1061X), carriers of the same mutation without left ventricular hypertrophy, as well as in unselected consecutive patients with HCM, and respective controls. METHODS: Anterior mitral valve leaflet (AML) and posterior mitral valve leaflet (PML) lengths were measured by CMR in 47 subjects with the Q1061X mutation in the gene encoding MYBPC3 and in 20 healthy relatives without the mutation. In addition, mitral valve leaflet lengths were measured by CMR in 80 consecutive non-genotyped patients with HCM in CMR and 71 age- and gender-matched healthy subjects. RESULTS: Of the subjects with the MYBPC-Q1016X mutation, 32 had left ventricular hypertrophy (LVH, LV maximal wall thickness >= 13 mm in CMR) and 15 had no hypertrophy. PML was longer in patients with the MYBPC3-Q1061X mutation and LVH than in controls of the MYBPC group (12.8 +/- 2.8 vs 10.6 +/- 1.9 mm, P = 0.013), but the difference between the groups was not statistically significant when PML was indexed for BSA (P = 0.066), or when PML length was adjusted for BSA, age, gender, LV mass and ejection fraction (P = 0.195). There was no significant difference in the PML length in mutation carriers without LVH and controls (11.1 +/- 3.4 vs 10.6 +/- 1.9, P = 0.52). We found no difference in AML lengths between the MYBPC mutation carriers with or without hypertrophy and controls. In 80 consecutive non-genotyped patients with HCM, there was no difference either in AML or PML lengths in subjects with HCM compared to respective control subjects. CONCLUSIONS: In subjects with HCM caused by the Q1061X mutation in the MYBPC3 gene, the posterior mitral valve leaflets may be elongated, but mitral valve elongation does not constitute primary phenotypic expression of the disease. Instead, elongated mitral valve leaflets seem to be associated with body size and left ventricular remodeling. PMID- 27259863 TI - Technical and Clinical Outcomes Following Colonic Stenting: A Seven-Year Analysis of 268 Procedures. AB - AIMS: To assess the factors contributing to the technical and clinical success of colorectal stenting for large bowel obstruction. METHODOLOGY: 268 cases of colonic stenting for large bowel obstruction were performed in 249 patients of mean age of 72 years (28-98) between 2006 and 2013. The majority of strictures were due to malignant disease, 244/268 (91 %). Diverticular strictures accounted for 24/268 (9 %). RESULTS: Overall technical success rate was 81 % (217/268), with a clinical success rate of 65 % (174/268). Duration of symptoms ranged from 0 to 180 days (mean 8 days). Technical success rate was seen to decrease with increasing symptom duration. For symptom duration of less than 1 week, technical success was 85.4 % (181/212) versus 69.6 % (39/56) for those with symptoms of greater than a week (p < 0.05). Clinical success rates fell from 71.3 % (107/150) to 59.3 % (70/118) (p < 0.05) when attempting to stent lesions of greater than 5 cm. There was also a significant reduction in clinical success when stenting lesions on a bend rather than a straight segment of colon 75.7 % (109/144) versus 59.7 % (74/124) (p < 0.05). A total of 20 (7.46 %) perforations were identified during the study. Stent migration occurred in 6.6 % of cases. In-stent stenosis occurred in 3.3 %. The overall 30-day all cause mortality rate was 9 %. CONCLUSION: Lesion size, location and duration of obstructive symptoms are statistically significant determinants of patient outcome. These factors could be used to advise patient selection for colonic stenting or direct progression to surgical intervention. PMID- 27259864 TI - Successful Management of Neobladder Variceal Bleeding. AB - Hematuria from a neobladder can occur due to a variety of pathologies including tumors, stones, and fistulas. Variceal bleeding in a neobladder is a very rare condition with only one case reported in literature. We present a case of a patient with cirrhosis and portal hypertension and an ileocolic orthotopic neobladder presenting with hematuria. Computed tomographic angiography showed dilated varices around the neobladder which were successfully embolized. To the best of our knowledge, this is the first report case of variceal bleeding in a neobladder successfully managed with the combination of TIPS (transjugular intrahepatic portosystemic shunt) procedure and embolization. PMID- 27259865 TI - Looking Beyond INR of 1.5 and Fresh Frozen Plasma in Liver Disease. PMID- 27259866 TI - MicroRNA-655-3p functions as a tumor suppressor by regulating ADAM10 and beta catenin pathway in Hepatocellular Carcinoma. AB - BACKGROUND: Increasing evidence suggests that microRNAs (miRNAs) play critical roles in malignant transformation, tumor progression and metastasis. Aberrant miR 655-3p expression has been associated with several cancers. However, the role and underlying mechanism of miR-655-3p in the development of hepatocellular carcinoma (HCC) remains unclear. METHODS: MiR-655-3p expression was detected by quantitative RT-PCR (qRT-PCR) in human HCC tissues and cell lines. Cell proliferation was investigated using MTT and colony formation assays, and cell migration and invasion abilities were evaluated by transwell assay. ADAM10 protein expression was detected by immunohistochemical assay. The target gene and downstream of miR-655-3p were determined by qRT-PCR, western blot and dual luciferase reporter assays. RESULTS: miR-655-3p was significantly down-regulated in HCC tissues and HCC cell lines. Low miR-655-3p expression was negatively related to tumor size, portal vein tumor thrombosis (PVTT) status, TNM stage and metastasis status. In addition, miR-655-3p overexpression and depletion decreased and increased HCC cell proliferation, migration and invasion, respectively. Moreover, ADAM10 was identified as a direct target of miR-655-3p, and miR-655-3p down-regulated E-cadherin protein level and inhibits beta-catenin pathway by mediating ADAM10. CONCLUSIONS: MiR-655-3p might functions as a tumor suppressor by directly targeting ADAM10 and indirectly regulating beta-catenin pathway in the development of progression of HCC. It may be a novel therapeutic candidate target to in HCC treatment. PMID- 27259868 TI - Applied Use of Safety Event Occurrence Control Charts of Harm and Non-Harm Events: A Case Study. AB - Most hospitals use occurrence reporting systems that facilitate identifying serious events that lead to root cause investigations. Thus, the events catalyze improvement efforts to mitigate patient harm. A serious limitation is that only a few of the occurrences are investigated. A challenge is leveraging the data to generate knowledge. The goal is to present a methodology to supplement these incident assessment efforts. The framework affords an enhanced understanding of patient safety through the use of control charts to monitor non-harm and harm incidents simultaneously. This approach can identify harm and non-harm reporting rates and also can facilitate monitoring occurrence trends. This method also can expedite identifying changes in workflow, processes, or safety culture. Although unable to identify root causes, this approach can identify changes in near real time. This approach also supports evaluating safety or policy interventions that may not be observable in annual safety climate surveys. PMID- 27259867 TI - Genetic environment of the KPC gene in Acinetobacter baumannii ST2 clone from Puerto Rico and genomic insights into its drug resistance. AB - Carbapenems are considered the last-resort antibiotics to treat infections caused by multidrug-resistant Gram-negative bacilli. The Klebsiella pneumoniae carbapenemase (KPC) enzyme hydrolyses beta-lactam antibiotics including the carbapenems. KPC has been detected worldwide in Enterobacteriaceae and Pseudomonas aeruginosa isolates associated with transposon Tn4401 commonly located in plasmids. Acinetobacter baumannii has become an important multidrug resistant nosocomial pathogen. KPC-producing A. baumannii has been reported to date only in Puerto Rico. The objective of this study was to determine the whole genomic sequence of a KPC-producing A. baumannii in order to (i) define its allelic diversity, (ii) identify the location and genetic environment of the blaKPC and (iii) detect additional mechanisms of antimicrobial resistance. Next generation sequencing, Southern blot, PFGE, multilocus sequence typing and bioinformatics analysis were performed. The organism was assigned to the international ST2 clone. The blaKPC-2 was identified on a novel truncated version of Tn4401e (tentatively named Tn4401h), located in the chromosome within an IncA/C plasmid fragment derived from an Enterobacteriaceae, probably owing to insertion sequence IS26. A chromosomally located truncated Tn1 transposon harbouring a blaTEM-1 was found in a novel genetic environment within an antimicrobial resistance cluster. Additional resistance mechanisms included efflux pumps, non-beta-lactam antibiotic inactivating enzymes within and outside a resistance island, two class 1 integrons, In439 and the novel In1252, as well as mutations in the topoisomerase and DNA gyrase genes which confer resistance to quinolones. The presence of the blaKPC in an already globally disseminated A. baumannii ST2 presents a serious threat of further dissemination. PMID- 27259869 TI - Effect of a Financial Incentive for Colorectal Cancer Screening Adherence on the Appropriateness of Colonoscopy Orders. AB - Performance incentives for preventive care may encourage inappropriate testing, such as cancer screening for patients with short life expectancies. Defining screening colonoscopies for patients with a >50% 4-year mortality risk as inappropriate, the authors performed a pre-post analysis assessing the effect of introducing a cancer screening incentive on the proportion of screening colonoscopy orders that were inappropriate. Among 2078 orders placed by 23 attending physicians in 4 academic general internal medicine practices, only 0.6% (n = 6/1057) of screening colonoscopy orders in the preintervention period and 0.6% (n = 6/1021) of screening colonoscopy orders in the postintervention period were deemed "inappropriate." This study found no evidence that the incentive led to an increase in inappropriate screening colonoscopy orders. PMID- 27259870 TI - Evaluating the Effect of Physician Fellowship Programs on Surgical Outcomes for Coronary Artery Bypass Grafting Procedures. AB - This study examined the relationship between fellowship training of thoracic surgeons and their patient outcomes following a coronary artery bypass graft (CABG) procedure. The study used data obtained from hospital discharges from Florida hospitals from 2006 to 2010 and linked them with the quality of the hospital wherein the physician completed his or her fellowship. Quality rankings were based on the hospital's national ranking among cardiovascular hospitals at the time when the fellowship was completed. A risk-adjusted analysis showed that completing a fellowship in a nationally ranked cardiovascular hospital and a longer time since fellowship and residency completion were associated with lower complication rates for CABG surgeries. This is the first study to incorporate hospital discharge data, external hospital quality rankings, and physician training characteristics to evaluate patient outcomes. Such knowledge could help shape the future direction of health care training and provide an objective, outcomes-based evaluation method for physician training programs. PMID- 27259872 TI - Do ACGME Physician-Patient Communication Milestones Align With HCAHPS Patient Satisfaction Measures for Doctor Communication? PMID- 27259871 TI - Development and Implementation of a Collaborative Team Care Model for Effective Insulin Use in an Academic Medical Center Primary Care Network. AB - Improving glycemic control across a primary care diabetes population is challenging. This article describes the development, implementation, and outcomes of the Diabetes Care Collaborative Model (DCCM), a collaborative team care process focused on promoting effective insulin use targeting patients with hyperglycemia in a patient-centered medical home model. After a pilot, the DCCM was implemented in 18 primary care practices affiliated with an academic medical center. Its implementation was associated with improvements in glycemic control and increase in insulin prescription longitudinally and across the entire population, with a >1% reduction in the proportion of glycated hemoglobin >9% at 2 years after the implementation compared with the 2 years prior ( P < .001). Facilitating factors included diverse stakeholder engagement, institutional alignment of priorities, awarding various types of credits for participation and implementation to providers, and a strong theoretical foundation using the principles of the collaborative care model. PMID- 27259873 TI - Monthly "Grief Rounds" to Improve Residents' Experience and Decrease Burnout in a Medical Intensive Care Unit Rotation. PMID- 27259874 TI - Can Webinar-Based Education Improve Geriatrics Training in Internal Medicine Residency Programs? PMID- 27259875 TI - Optimizing Prescribing Practices of High-Cost Medications With Computerized Alerts in the Inpatient Setting. AB - Current literature does not consistently show a benefit to providing medication cost information to inpatient health care prescribers. This study assessed the effectiveness of computerized provider order entry alerts that displayed the cost of a high-cost medication alongside a lower cost alternative, targeting 3 high cost medications. Medication utilization during the one year prior to the intervention was compared to usage in the year after implementation. Reduced utilization of high-cost medications was found when comparing pre to post. Ipratropium hydrofluoroalkane and fluticasone hydrofluoroalkane metered dose inhaler utilization were reduced by 29% and 62%, respectively ( P < .001 for both). A 71% decrease in intravenous chlorothiazide was observed ( P < .001); however, its effect was unable to be separated from implementation of a heart failure diuretic protocol during the study period. Overall, these results suggest computerized medication cost alerts that recommend a lower cost therapeutic alternative are effective in changing prescribing practices. PMID- 27259876 TI - A Wireless Text Messaging System Improves Communication for Neonatal Resuscitation. AB - Handoffs for neonatal resuscitation involve communicating critical delivery information (CDI). The authors sought to achieve >=95% communication of CDI during resuscitation team requests. CDI included name of caller, urgency of request, location of delivery, gestation of fetus, status of amniotic fluid, and indication for presence of the resuscitation team. Three interventions were implemented: verbal scripted handoff, Spok text messaging, and Engage text messaging. Percentages of CDI communications were analyzed using statistical process control. Following implementation of Engage, the communication of all CDI, except for indication, was >=95%; communication of indication occurred 93% of the time. Control limits for most CDI were narrower with Engage, indicating greater reliability of communication compared to the verbal handoff and Spok. Delayed resuscitation team arrival, a countermeasure, was not higher with text messaging compared to verbal handoff ( P = 1.00). Text messaging improved communication during high-risk deliveries, and it may represent an effective tool for other delivery centers. PMID- 27259877 TI - Developing an Interdisciplinary, Team-Based Quality Improvement Leadership Training Program for Clinicians: The Partners Clinical Process Improvement Leadership Program. AB - Although there has been tremendous progress in quality improvement (QI) education for students and trainees in recent years, much less has been published regarding the training of active clinicians in QI. The Partners Clinical Process Improvement Leadership Program (CPIP) is a 6-day experiential program. Interdisciplinary teams complete a QI project framed by didactic sessions, interactive exercises, case-based problem sessions, and a final presentation. A total of 239 teams composed of 516 individuals have graduated CPIP. On completion, participant satisfaction scores average 4.52 (scale 1-5) and self reported understanding of QI concepts improved. At 6 months after graduation, 66% of survey respondents reported sustained QI activity. Three opportunities to improve the program have been identified: (1) increasing faculty participation through online and tiered course offerings, (2) integrating the faculty-focused program with the trainee curriculum, and (3) developing a postgraduate curriculum to address the challenges of sustained improvement. PMID- 27259878 TI - Impact of an Enhanced Transition Process on Patient Readiness for Discharge. PMID- 27259879 TI - Microplastic Ingestion by Wild and Cultured Manila Clams (Venerupis philippinarum) from Baynes Sound, British Columbia. AB - Microplastics, plastic particles <5 mm, are an emerging concern in aquatic ecosystems. Because microplastics are small, they are available to many filter feeding organisms, which can then be consumed by higher trophic level organisms, including humans. This study documents the quantity of microplastics present in wild and cultured Manila clams (Venerupis philippinarum). Three active shellfish farms and three reference beaches (i.e., non-shellfish farm sites) in Baynes Sound, British Columbia were chosen to examine the microplastic concentrations in wild and cultured Manila clams. Microplastics were isolated using a nitric acid digestion technique and enumerated from 54 clams (27 farmed and 27 non-farmed). Qualitative attributes, such as colour and microplastic type (fiber, fragment, or film) also were recorded. There was no significant difference (F = 1.29; df = 1,4; P = 0.289) between microplastic concentrations in cultured and wild clams. Microplastic concentrations ranged from 0.07 to 5.47 particles/g (from reference beach and shellfish farm clams, respectively). Fibers were the dominant microplastic (90 %); colourless and dark gray fibers were the most common colours observed (36 and 26 %, respectively). Although this indicates that microplastics are definitely present in seafood consumed by humans, shellfish aquaculture operations do not appear to be increasing microplastic concentrations in farmed clams in this region. PMID- 27259882 TI - The dream of imaging coronary artery inflammation with FDG PET/CT imaging. PMID- 27259880 TI - Effects of CYP-Induced Cystitis on Growth Factors and Associated Receptor Expression in Micturition Pathways in Mice with Chronic Overexpression of NGF in Urothelium. AB - We have determined if cyclophosphamide (CYP)-induced cystitis produces additional changes in growth factor/receptors expression in the urinary bladder (urothelium, detrusor) and lumbosacral (L6-S1) dorsal root ganglia (DRG) in a transgenic mouse model with chronic urothelial overexpression of NGF (NGF-OE). Functionally, NGF OE mice treated with CYP exhibit significant increases in voiding frequency above that observed in control NGF-OE mice (no CYP). Quantitative PCR was used to determine NGF, BDNF, VEGF, and receptors (TrkA, TrkB, p75(NTR)) transcripts expression in tissues from NGF-OE and wild-type (WT) mice with CYP-induced cystitis of varying duration (4 h, 48 h, 8 days). In urothelium of control NGF-OE mice, NGF mRNA was significantly (p <= 0.001) increased. Urothelial expression of NGF mRNA in NGF-OE mice treated with CYP (4 h, 48 h, 8 days) was not further increased but maintained with all durations of CYP treatment evaluated. In contrast, CYP-induced cystitis (4 h, 48 h, 8 days) in NGF-OE mice demonstrated significant (p <= 0.05) regulation in BDNF, VEGF, TrkA, TrkB, and P75(NTR) mRNA in urothelium and detrusor smooth muscle. Similarly, CYP-induced cystitis (4 h, 48 h, 8 days) in NGF-OE mice resulted in significant (p <= 0.05), differential changes in transcript expression for NGF, BDNF, and receptors (TrkA, TrkB, p75(NTR)) in S1 DRG that was dependent on the duration-of CYP-induced cystitis. In general, NGF, BDNF, TrkA, and TrkB protein content in the urinary bladder increased in WT and NGF-OE mice with CYP-induced cystitis (4 h). Changes in NGF, TrkA and TrkB expression in the urinary bladder were significantly (p <= 0.05) greater in NGF-OE mice with CYP-induced cystitis (4 h) compared to WT mice with cystitis (4 h). However, the magnitude of change between WT and NGF-OE mice was only significantly (p <= 0.05) different for TrkB expression in urinary bladder of NGF-OE mice treated with CYP. These studies are consistent with target-derived NGF and other inflammatory mediators affecting neurochemical plasticity with potential contributions to reflex function of micturition pathways. PMID- 27259883 TI - Effect of aminophylline administration on the diagnostic yield of vasodilator myocardial perfusion imaging. PMID- 27259884 TI - [Everyday life with HIV: everything "normal"?]. PMID- 27259885 TI - [New backbone for HIV therapy. F/TAV: long-term improved renal and osseous safety profile]. PMID- 27259886 TI - [This far it can go without HIV therapy!]. PMID- 27259887 TI - [HIV infection and pregnancy. Improved therapy management for HIV infected pregnant patients]. PMID- 27259888 TI - [Attending to life style and comorbidities. Comprehensive management of HIV patients]. PMID- 27259889 TI - [This is how the "gene scissors" function against HIV]. PMID- 27259890 TI - [Healing of HIV. Legitimate hope or utopia?]. PMID- 27259891 TI - [PrEP (pre-exposure prophylaxis) for women: what are the benefits of the vaginal ring?]. PMID- 27259892 TI - [Protection against HIV - but only with good compliance!]. PMID- 27259893 TI - [In syphilis: penicillin iv]. PMID- 27259894 TI - [Against tripper soon almost no herb is effective]. PMID- 27259895 TI - ["Influenza vaccination for every HIV patient"]. PMID- 27259896 TI - [HIV in the Limelight]. PMID- 27259897 TI - [The phenomenon of an open window]. PMID- 27259898 TI - [HIV at the workplace: what should be considered - which problems can arise?]. PMID- 27259899 TI - [When supplementation is needed]. PMID- 27259900 TI - [HIV and sports: good or evil?]. PMID- 27259901 TI - [Vaccinations and prophylaxis: what to consider]. PMID- 27259902 TI - [HIV & relationship - what if only one of the partners is HIV positive?]. PMID- 27259903 TI - [HIV, desire to have a child and pregnancy: new aspects]. PMID- 27259904 TI - [HIV - Individualized therapy is announced]. PMID- 27259905 TI - [Chronic Hepatitis C - Therapeutic Options in 2016]. PMID- 27259906 TI - [EMA examines an application for change in authorization of truvada]. PMID- 27259907 TI - [Optimized therapy]. PMID- 27259908 TI - [Declining costs]. PMID- 27259909 TI - [LDV/SOF successful in general practice test]. PMID- 27259910 TI - [In HIV-HCV co-infection check for drug interactions]. PMID- 27259912 TI - [Combination of tacrolimus and MMF for treatment of proliferative lupus nephritis]. PMID- 27259913 TI - [Psoriatic arthritis : Overview of drug therapy options and administration characteristics]. AB - Psoriatic arthritis is a chronic inflammatory disease of the musculoskeletal system with association to skin psoriasis and is characterized by variable clinical symptoms with very heterogeneous degrees of disease suffering for patients. Clinical manifestations essentially include alterations to the skin and nails, peripheral arthritis, enthesitis, dactylitis and/or spinal involvement. This variability necessitates an individualized therapy of patients with different therapy targets. Apart from international guidelines no therapy recommendations are available in Germany for treatment of psoriatic arthritis. For this reason this article summarizes the established points, characteristics and aspects to be considered in the therapy of psoriatic arthritis in Germany, taking the various main forms of the disease into consideration. PMID- 27259914 TI - Towards Consensus Gene Ages. AB - Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene's age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID- 27259915 TI - Design and validation of a questionnaire to evaluate the usability of computerized critical care information systems. AB - The implementation of computerized critical care information systems (CCIS) can improve the quality of clinical care and staff satisfaction, but also holds risks of disrupting the workflow with consecutive negative impacts. The usability of CCIS is one of the key factors determining their benefits and weaknesses. However, no tailored instrument exists to measure the usability of such systems. Therefore, the aim of this study was to design and validate a questionnaire that measures the usability of CCIS. Following a mixed-method design approach, we developed a questionnaire comprising two evaluation models to assess the usability of CCIS: (1) the task-specific model rates the usability individually for several tasks which CCIS could support and which we derived by analyzing work processes in the ICU; (2) the characteristic-specific model rates the different aspects of the usability, as defined by the international standard "ergonomics of human-system interaction". We tested validity and reliability of the digital version of the questionnaire in a sample population. In the sample population of 535 participants both usability evaluation models showed a strong correlation with the overall rating of the system (multiple correlation coefficients >=0.80) as well as a very high internal consistency (Cronbach's alpha >=0.93). The novel questionnaire is a valid and reliable instrument to measure the usability of CCIS and can be used to study the influence of the usability on their implementation benefits and weaknesses. PMID- 27259916 TI - Erratum to: Aggregation and Competitive Exclusion: Explaining the Coexistence of Human Papillomavirus Types and the Effectiveness of Limited Vaccine Conferred Cross-Immunity. PMID- 27259917 TI - Tailored flow sequestration treatment using high-flow and low-flow bypass for partially thrombosed giant internal carotid artery aneurysm-a technical case report. AB - Direct clipping of giant partially thrombosed intracranial internal carotid artery (ICA) aneurysms is challenging, especially when important perforating arteries are involved. Proximal occlusion with bypass represents a possible alternative approach. An 80-year-old female presented with worsening visual acuity and severe headache caused by partially thrombosed giant (38 mm in diameter) aneurysms of the right ICA, suggestive of impending rupture. Direct clipping in conjunction with temporary occlusion of the lesion involving the anterior choroidal artery (AChA) was considered too risky. Thus, we sequestrated the ipsilateral ICA flow into a low-flow and a high-flow system using two external carotid artery (ECA)-ICA bypasses and one in situ bypass with cervical ICA ligation. As a result, the low-flow system by the superficial temporal artery middle cerebral artery (MCA) bypass perfused mainly the proximal MCA lesions and aneurysm, whereas the high-flow system by ECA-radial artery-M2 bypass exclusively supplied the residual distal MCA area. This tailored flow sequestration successfully interrupted intra-aneurysmal flow and accelerated near-complete thrombosis of the aneurysm while preserving the AChA and avoiding any significant neurological deterioration. We conclude that this method is effective for the management of giant partially thrombosed aneurysms of the ICA, especially when direct clipping is difficult. PMID- 27259918 TI - Helios((r)) Gene Gun-Mediated Transfection of the Inner Ear Sensory Epithelium: Recent Updates. AB - The transfection of vertebrate inner ear hair cells has proven to be challenging. Therefore, many laboratories attempt to use and improve different transfection methods. Each method has its own advantages and disadvantages. A particular researcher's skills in addition to available equipment and the type of experiment (in vivo or in vitro) likely determine the transfection method of choice. Biolistic delivery of exogenous DNA, mRNA, or siRNA, also known as Helios((r)) Gene Gun-mediated transfection, uses the mechanical energy of compressed helium gas to bombard tissue with micron- or submicron-sized DNA or RNA-coated gold particles, which can penetrate and transfect cells in vitro or in vivo. Helios((r)) Gene Gun-mediated transfection has several advantages: (1) it is simple enough to learn in a short time; (2) it is designed to overcome cell barriers even as tough as plant cell membrane or stratum corneum in the epidermis; (3) it can transfect cells deep inside a tissue such as specific neurons within a brain slice; (4) it can accommodate mRNA, siRNA, or DNA practically of any size to be delivered; and (5) it works well with various cell types including non-dividing, terminally differentiated cells that are difficult to transfect, such as neurons or mammalian inner ear sensory hair cells. The latter advantage is particularly important for inner ear research. The disadvantages of this method are: (1) low efficiency of transfection due to many variables that have to be adjusted and (2) potential mechanical damage of the tissue if the biolistic shot parameters are not optimal. This chapter provides a step-by-step protocol and critical evaluation of the Bio-Rad Helios((r)) Gene Gun transfection method used to deliver green fluorescent protein (GFP)-tagged full length cDNAs of myosin 15a, whirlin, beta-actin, and Clic5 into rodent hair cells of the postnatal inner ear sensory epithelia in culture. PMID- 27259919 TI - Tol2-Mediated Delivery of miRNAs to the Chicken Otocyst Using Plasmid Electroporation. AB - The avian embryo has a well-documented history as a model system for the study of neurogenesis, morphogenesis, and cell fate specification. This includes studies of the chicken inner ear that employ in ovo electroporation, in conjunction with the Tol2 system, to yield robust long-term transgene expression. Capitalizing on the success of this delivery method, we describe a modified version of the Tol2 expression vector that readily accepts the insertion of a microRNA-encoding artificial intron. This offers a strategy to investigate the possible roles of different candidate microRNAs in ear development by overexpression. Here, we describe the general design of this modified vector and the electroporation procedure. This approach is expected to facilitate phenotypic screening of candidate miRNAs to explore their bioactivity in vivo. PMID- 27259920 TI - A Rapid, Cost-Effective Method to Prepare Recombinant Adeno-Associated Virus for Efficient Gene Transfer to the Developing Mouse Inner Ear. AB - There is keen interest to define gene therapies aimed at restoration of auditory and vestibular function in the diseased or damaged mammalian inner ear. A persistent limitation of regenerative medical strategies that seek to correct or modify gene expression in the sensory epithelia of the inner ear involves efficacious delivery of a therapeutic genetic construct. Our approach is to define methodologies that enable fetal gene transfer to the developing mammalian inner ear in an effort to correct defective gene expression during formation of the sensory epithelia or during early postnatal life. Conceptually, the goal is to atraumatically introduce the genetic construct into the otocyst-staged mouse inner ear and transfect otic progenitors that give rise to sensory hair cells and supporting cells. Our long-term goal is to define therapeutic interventions for congenital deafness and balance disorders with the expectation that the approach may also be exploited for therapeutic intervention postnatally.In the inaugural volume of this series, we introduced electroporation-mediated gene transfer to the developing mouse inner ear that encompassed our mouse survival surgery and transuterine microinjection protocols (Brigande et al., Methods Mol Biol 493:125 139, 2009). In this chapter, we first briefly update our use of sodium pentobarbital anesthesia, our preferred anesthetic for mouse ventral laparotomy, in light of its rapidly escalating cost. Next, we define a rapid, cost-effective method to produce recombinant adeno-associated virus (rAAV) for efficient gene transfer to the developing mouse inner ear. Our immediate goal is to provide a genetic toolkit that will permit the definition and validation of gene therapies in mouse models of human deafness and balance disorders. PMID- 27259921 TI - Generation of Noninvasive, Quantifiable, Orthotopic Animal Models for NF2 Associated Schwannoma and Meningioma. AB - Schwannomas and meningiomas are nervous system tumors that can occur sporadically or in patients with neurofibromatosis type 2 (NF2). Mutations of the Neurofibromatosis 2 (NF2) gene are frequently observed in these tumors. Schwannomas and meningiomas cause significant morbidities, and an FDA-approved medical therapy is currently not available. The development of preclinical animal models that accurately capture the clinical characteristics of these tumors will facilitate the evaluation of novel therapeutic agents for the treatment of these tumors, ultimately leading to more productive clinical trials. Here, we describe the generation of luciferase-expressing NF2-deficient schwannoma and meningioma cells and the use of these cells to establish orthotopic tumor models in immunodeficient mice. The growth of these tumors and their response to treatment can be measured effectively by bioluminescence imaging (BLI) and confirmed by small-animal magnetic resonance imaging (MRI). These and other animal models, such as genetically-engineered models, should substantially advance the investigation of promising therapies for schwannomas and meningiomas. PMID- 27259922 TI - RNA Extraction from Xenopus Auditory and Vestibular Organs for Molecular Cloning and Expression Profiling with RNA-Seq and Microarrays. AB - The amphibian Xenopus offers a unique model system for uncovering the genetic basis of auditory and vestibular function in an organism that is well-suited for experimental manipulation during animal development. However, many procedures for analyzing gene expression in the peripheral auditory and vestibular systems mandate the ability to isolate intact RNA from inner ear tissue. Methods presented here facilitate preparation of high-quality inner ear RNA from larval and post-metamorphic Xenopus specimens that can be used for a variety of purposes. We demonstrate that RNA isolated with these protocols is suitable for microarray analysis and Illumina-Solexa sequencing (RNA-Seq) of inner ear organs, and for cloning of large transcripts, such as those for ion channels. Genetic sequences cloned with these procedures can be used for transient transfection of Xenopus kidney cell lines with fluorescent protein fusion constructs. PMID- 27259923 TI - Yeast Two-Hybrid Screening to Test for Protein-Protein Interactions in the Auditory System. AB - We describe a protocol to screen for protein-protein interactions using the Gal-4 based yeast two-hybrid system. In this protocol, we describe serial transformation of bait into an already constructed cDNA library in yeast AH109 cells. We find this method gives the most number of true interactions. Where a premade library in yeast cells is not available, the method outlined can be quickly adapted. AH109 cells can be first transformed with bait containing a vector followed by selection of yeast containing the bait. A second transformation of yeast cells is then accomplished with the cDNA library. The method is quick and can lead to the discovery of significant interactions. PMID- 27259924 TI - Multiplexed Isobaric Tagging Protocols for Quantitative Mass Spectrometry Approaches to Auditory Research. AB - Modern biologists have at their disposal a large array of techniques used to assess the existence and relative or absolute quantity of any molecule of interest in a sample. However, implementing most of these procedures can be a daunting task for the first time, even in a lab with experienced researchers. Just choosing a protocol to follow can take weeks while all of the nuances are examined and it is determined whether a protocol will (a) give the desired results, (b) result in interpretable and unbiased data, and (c) be amenable to the sample of interest. We detail here a robust procedure for labeling proteins in a complex lysate for the ultimate differential quantification of protein abundance following experimental manipulations. Following a successful outcome of the labeling procedure, the sample is submitted for mass spectrometric analysis, resulting in peptide quantification and protein identification. While we will concentrate on cells in culture, we will point out procedures that can be used for labeling lysates generated from tissues, along with any minor modifications required for such samples. We will also outline, but not fully document, other strategies used in our lab to label proteins prior to mass spectrometric analysis, and describe under which conditions each procedure may be desirable. What is not covered in this chapter is anything but the most brief introduction to mass spectrometry (instrumentation, theory, etc.), nor do we attempt to cover much in the way of software used for post hoc analysis. These two topics are dependent upon one's resources, and where applicable, one's collaborators. We strongly encourage the reader to seek out expert advice on topics not covered here. PMID- 27259925 TI - Protein Quantitation of the Developing Cochlea Using Mass Spectrometry. AB - Mass spectrometry-based proteomics allows for the measurement of hundreds to thousands of proteins in a biological system. Additionally, mass spectrometry can also be used to quantify proteins and peptides. However, observing quantitative differences between biological systems using mass spectrometry-based proteomics can be challenging because it is critical to have a method that is fast, reproducible, and accurate. Therefore, to study differential protein expression in biological samples labeling or label-free quantitative methods can be used. Labeling methods have been widely used in quantitative proteomics, however label free methods have become equally as popular and more preferred because they produce faster, cleaner, and simpler results. Here, we describe the methods by which proteins are isolated and identified from cochlear sensory epithelia tissues at different ages and quantitatively differentiated using label-free mass spectrometry. PMID- 27259926 TI - Ultrastructural Identification and Colocalization of Interacting Proteins in the Murine Cochlea by Post-Embedding Immunogold Transmission Electron Microscopy. AB - Verification of the presence and location of a protein within tissue can be accomplished by western blotting and immunohistochemistry, using either paraffin or frozen sections. Affinity purification by reciprocal coimmunoprecipitations using the tissue of interest can demonstrate the existence of an interacting pair of proteins. Ultimately, the ability to visualize the interaction at the cellular level is desired. Precise location(s) of interacting proteins in situ can be accomplished by ultrastructural localization with high-quality primary antibodies and small-particle-size Au-conjugated secondary antibodies. Visualization can be obtained with a transmission electron microscope fitted with a high-resolution camera permitting magnifications that exceed 2 * 10(5), and, to date, resolution capability of 20+ Mpixels, thus enabling localization of the target protein to within nanometers of the actual location. Here, we report the method by which immunolocalization at the level of the electron microscope is accomplished using the post-embedding technique, i.e., performing antibody labeling of proteins on ultrathin sections of tissue embedded in acrylic resin. PMID- 27259927 TI - Surface Plasmon Resonance (SPR) Analysis of Binding Interactions of Inner-Ear Proteins. AB - Surface plasmon resonance is an optical technique that is utilized for detecting molecular interactions. Binding of a mobile molecule (analyte) to a molecule immobilized on a thin metal film (ligand) changes the refractive index of the film. The angle of extinction of light that is completely reflected after polarized light impinges upon the film, is altered, and monitored as a change in detector position for a dip in reflected intensity (the surface plasmon resonance phenomenon). Because the method strictly detects mass, there is no need to label the interacting components, thus eliminating possible changes of their molecular properties. We have utilized surface plasmon resonance to study interaction of proteins of inner-ear sensory epithelia. PMID- 27259928 TI - The Single-Molecule Approach to Membrane Protein Stoichiometry. AB - The advent of techniques for imaging solitary fluorescent molecules has made possible many new kinds of biological experiments. Here, we describe the application of single-molecule imaging to the problem of subunit stoichiometry in membrane proteins. A membrane protein of unknown stoichiometry, prestin, is coupled to the fluorescent enhanced green fluorescent protein (eGFP) and synthesized in the human embryonic kidney (HEK) cell line. We prepare adherent membrane fragments containing prestin-eGFP by osmotic lysis. The molecules are then exposed to continuous low-level excitation until their fluorescence reaches background levels. Their fluorescence decreases in discrete equal-amplitude steps, consistent with the photobleaching of single fluorophores. We count the number of steps required to photobleach each molecule. The molecular stoichiometry is then deduced using a binomial model. PMID- 27259929 TI - Visualization of Live Cochlear Stereocilia at a Nanoscale Resolution Using Hopping Probe Ion Conductance Microscopy. AB - The mechanosensory apparatus that detects sound-induced vibrations in the cochlea is located on the apex of the auditory sensory hair cells and it is made up of actin-filled projections, called stereocilia. In young rodents, stereocilia bundles of auditory hair cells consist of 3-4 rows of stereocilia of decreasing height and varying thickness. Morphological studies of the auditory stereocilia bundles in live hair cells have been challenging because the diameter of each stereocilium is near or below the resolution limit of optical microscopy. In theory, scanning probe microscopy techniques, such as atomic force microscopy, could visualize the surface of a living cell at a nanoscale resolution. However, their implementations for hair cell imaging have been largely unsuccessful because the probe usually damages the bundle and disrupts the bundle cohesiveness during imaging. We overcome these limitations by using hopping probe ion conductance microscopy (HPICM), a non-contact scanning probe technique that is ideally suited for the imaging of live cells with a complex topography. Organ of Corti explants are placed in a physiological solution and then a glass nanopipette-which is connected to a 3D-positioning piezoelectric system and to a patch clamp amplifier-is used to scan the surface of the live hair cells at nanometer resolution without ever touching the cell surface.Here, we provide a detailed protocol for the imaging of mouse or rat stereocilia bundles in live auditory hair cells using HPICM. We provide information about the fabrication of the nanopipettes, the calibration of the HPICM setup, the parameters we have optimized for the imaging of live stereocilia bundles and, lastly, a few basic image post-processing manipulations. PMID- 27259930 TI - Design and Construction of a Cost-Effective Spinning Disk System for Live Imaging of Inner Ear Tissue. AB - Confocal imaging of fluorescent probes offers a powerful, non-invasive tool which enables data collection from vast population of cells at high spatial and temporal resolution. Spinning disk confocal microscopy parallelizes the imaging process permitting the study of dynamic events in populations of living cells on the millisecond time scale. Several spinning disk microscopy solutions are commercially available, however these are often poorly configurable and relatively expensive. This chapter describes a procedure to assemble a cost effective homemade spinning disk system for fluorescence microscopy, which is highly flexible and easily configurable. We finally illustrate a reliable protocol to obtain high-quality Ca(2+) and voltage imaging data from cochlear preparations. PMID- 27259932 TI - Detection of Excitatory and Inhibitory Synapses in the Auditory System Using Fluorescence Immunohistochemistry and High-Resolution Fluorescence Microscopy. AB - In sensory systems, a balanced excitatory and inhibitory circuit along the ascending pathway is not only important for the establishment of topographically ordered connections from the periphery to the cortex but also for temporal precision of signal processing. The accomplishment of spatial and temporal cortical resolution in the central nervous system is a process that is likely initiated by the first sensory experiences that drive a period of increased intracortical inhibition. In the auditory system, the time of first sensory experience is also the period in which a reorganization of cochlear efferent and afferent fibers occurs leading to the mature innervation of inner and outer hair cells. This mature hair cell innervation is the basis of accurate sound processing along the ascending pathway up to the auditory cortex. We describe here, a protocol for detecting excitatory and inhibitory marker proteins along the ascending auditory pathway, which could be a useful tool for detecting changes in auditory signal processing during various forms of hearing disorders. Our protocol uses fluorescence immunohistochemistry in combination with high resolution fluorescence microscopy in cochlear and brain tissue. PMID- 27259931 TI - Neuroanatomical Tracing Techniques in the Ear: History, State of the Art, and Future Developments. AB - The inner ear has long been at the cutting edge of tract tracing techniques that have shaped and reshaped our understanding of the ear's innervation patterns. This review provides a historical framework to understand the importance of these techniques for ear innervation and for development of tracing techniques in general; it is hoped that lessons learned will help to quickly adopt transformative novel techniques and their information and correct past beliefs based on technical limitations. The technical part of the review presents details of our protocol as developed over the last 30 years. We also include arguments as to why these recommendations work best to generate the desired outcome of distinct fiber and cell labeling, and generate reliable data for any investigation. We specifically focus on two tracing techniques, in part developed and/or championed for ear innervation analysis: the low molecular multicolor dextran amine tract tracing technique and the multicolor tract tracing technique with lipophilic dyes. PMID- 27259933 TI - Rapid and Semi-automated Extraction of Neuronal Cell Bodies and Nuclei from Electron Microscopy Image Stacks. AB - Connectomics-the study of how neurons wire together in the brain-is at the forefront of modern neuroscience research. However, many connectomics studies are limited by the time and precision needed to correctly segment large volumes of electron microscopy (EM) image data. We present here a semi-automated segmentation pipeline using freely available software that can significantly decrease segmentation time for extracting both nuclei and cell bodies from EM image volumes. PMID- 27259934 TI - Organotypic Culture of the Mouse Cochlea from Embryonic Day 12 to the Neonate. AB - The development of the mammalian cochlea is a complex process involving several intersecting signaling pathways to ultimately generate its highly organized cellular architecture. In humans, and in the mouse, there is one row of inner hair cells aligned next to three rows of outer hair cells. The support cells intercalate between the hair cells to create a cellular mosaic across the organ of Corti (OC). Organotypic culture of the cochlea is a valuable technique for investigating the early stages of OC development. Cultures can be established at proliferative stages and maintained in vitro until cellular differentiation commences. It is straightforward to monitor differentiation in response to perturbations of key signaling pathways using pharmacological agents. While postnatal cochlea organ cultures have already been adapted for in vitro studies, it is more challenging to establish cultures at early embryonic stages due to the small size of the organ primordium. The protocol described in this chapter is permissive for all stages of development from E12 cochleas to day 5 neonatal murine cochleas, allowing culture survival up to 2 weeks in vitro. PMID- 27259935 TI - Quantifying Spiral Ganglion Neurite and Schwann Behavior on Micropatterned Polymer Substrates. AB - The first successful in vitro experiments on the cochlea were conducted in 1928 by Honor Fell (Fell, Arch Exp Zellforsch 7(1):69-81, 1928). Since then, techniques for culture of this tissue have been refined, and dissociated primary culture of the spiral ganglion has become a widely accepted in vitro model for studying nerve damage and regeneration in the cochlea. Additionally, patterned substrates have been developed that facilitate and direct neural outgrowth. A number of automated and semi-automated methods for quantifying this neurite outgrowth have been utilized in recent years (Zhang et al., J Neurosci Methods 160(1):149-162, 2007; Tapias et al., Neurobiol Dis 54:158-168, 2013). Here, we describe a method to study the effect of topographical cues on spiral ganglion neurite and Schwann cell alignment. We discuss our microfabrication process, characterization of pattern features, cell culture techniques for both spiral ganglion neurons and spiral ganglion Schwann cells. In addition, we describe protocols for reducing fibroblast count, immunocytochemistry, and methods for quantifying neurite and Schwann cell alignment. PMID- 27259936 TI - The Use of Human Wharton's Jelly Cells for Cochlear Tissue Engineering. AB - Tissue engineering focuses on three primary components: stem cells, biomaterials, and growth factors. Together, the combination of these components is used to regrow and repair damaged tissues that normally do not regenerate easily on their own. Much attention has been focused on the use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), due to their broad differentiation potential. However, ESCs and iPSCs require very detailed protocols to differentiate into target tissues, which are not always successful. Furthermore, procurement of ESCs is considered ethically controversial in some regions and procurement of iPSCs requires laborious transformation of adult tissues and characterization. However, mesenchymal stem cells are an adult stem cell population that are not ethically controversial and are readily available for procurement. Furthermore, mesenchymal stem cells exhibit the ability to differentiate into a variety of cell types arising from the mesoderm. In particular, human Wharton's jelly cells (hWJCs) are mesenchymal-type stem cells found in umbilical cords that possess remarkable differentiation potential. hWJCs are a highly desirable stem cell population due to their abundance in supply, high proliferation rates, and ability to differentiate into multiple cell types arising from all three germ layers. hWJCs are used to generate several neurological phenotypes arising from the ectoderm and are considered for engineering mechanosensory hair cells found in the auditory complex. Here, we report the methods for isolating hWJCs from human umbilical cords and non-virally transfected for use in cochlear tissue engineering studies. PMID- 27259937 TI - Nanotechnology in Auditory Research: Membrane Electromechanics in Hearing. AB - The soft, thin membranes that envelop all living cells are 2D, nanoscale, fluid assemblies of phospholipids, sterols, proteins, and other molecules. Mechanical interactions between these components facilitate membrane function, a key example of which is ion flow mediated by the mechanical opening and closing of channels. Hearing and balance are initiated by the modulation of ion flow through mechanoreceptor channels in stereocilia membranes. Cochlear amplification by the outer hair cell involves modulation of ion movement by the membrane protein prestin. Voltage-gated ion channels shape the receptor potential in hair cells and are responsible for the initiation of action potentials that are at the heart of sensory processing in the brain. All three processes require a membrane and their kinetics are modulated by the mechanical (i.e., material) properties of the membrane. This chapter reviews the methodology for measuring the mechanics of cellular membranes and introduces a method for examining membrane electromechanics. The approach allows examination of electromechanically mediated interactions between the different molecular species in the membrane that contribute to the biology of hearing and balance. PMID- 27259938 TI - An Overview of Nanoparticle Based Delivery for Treatment of Inner Ear Disorders. AB - Nanoparticles offer new possibilities for inner ear treatment as they can carry a variety of drugs, protein, and nucleic acids to inner ear. Nanoparticles are equipped with several functions such as targetability, immuno-transparency, biochemical stability, and ability to be visualized in vivo and in vitro. A group of novel peptides can be attached to the surface of nanoparticles that will enhance the cell entry, endosomal escape, and nuclear targeting. Eight different types of nanoparticles with different payload carrying strategies are available now. The transtympanic delivery of nanoparticles indicates that, depending on the type of nanoparticle, different migration pathways into the inner ear can be employed, and that optimal carriers can be designed according to the intended cargo. The use of nanoparticles as drug/gene carriers is especially attractive in conjunction with cochlear implantation or even as an inclusion in the implant as a drug/gene reservoir. PMID- 27259939 TI - Development of Cell-Based High-Throughput Chemical Screens for Protection Against Cisplatin-Induced Ototoxicity. AB - Various compounds have been tested in recent years for protection against cisplatin-induced hearing loss, but no compound has yet been FDA approved for clinical use in patients. Towards this goal, we developed an unbiased, high throughput, mammalian cochlear cell-based chemical screen that allowed quantification of the protection ability of bioactive compounds and ranked them for future testing ex vivo in cochlear explant cultures and in vivo in animal models. In our primary screens, protection in the HEI-OC1 organ of Corti immortalized cell line was measured by the ability of each compound to inhibit caspase-3/7 activity triggered by cisplatin treatment (50 MUM cisplatin for 22 h). A total of 4385 unique bioactive compounds were tested in a single dose of 8 MUM and promising compounds were validated by dose response curves covering ten, 1:3 serial diluted concentrations. Primary hits were defined as having more than 60 % inhibition of the caspase-3/7 activity. Toxicity of the top compounds was measured by a CellTiter-Glo (CTG) assay that measured the viability of the cells in the presence of compound alone in similar dose responsive analysis. A combination of the caspase-3/7 inhibition activity assay (as measured by IC50) and the CTG viability assay (as determined by LD50) identified the top protective compounds in the HEI-OC1 cells. In the future, the top hits in our screens will be tested for their protective ability ex vivo in mouse cochlear explants and in vivo in animal models. Our mammalian cochlear cell-based, high-throughput chemical screening assays described here can be further modified and represent an initial successful step towards therapeutic intervention of hearing disorders, an unmet medical need of our society. PMID- 27259940 TI - Profiling Specific Inner Ear Cell Types Using Cell Sorting Techniques. AB - Studies of specific tissue cell types are becoming increasingly important in advancing our understanding of cell biology and gene and protein expression. Prospective isolation of specific cell types is a powerful technique as it facilitates such investigations, allowing for analysis and characterization of individual cell populations. Such an approach to studying inner ear tissues presents a unique challenge because of the paucity of cells of interest and limited cell markers. In this chapter, we describe methods for selectively labeling and isolating different inner ear cell types from the neonatal mouse cochlea using fluorescence-activated cell sorting. PMID- 27259941 TI - Optical Coherence Tomography to Measure Sound-Induced Motions Within the Mouse Organ of Corti In Vivo. AB - The measurement of mechanical vibrations within the living cochlea is critical to understanding the first nonlinear steps in auditory processing, hair cell stimulation, and cochlear amplification. However, it has proven to be a challenging endeavor. This chapter describes how optical coherence tomography (OCT) can be used to measure vibrations within the tissues of the organ of Corti. These experimental measurements can be performed within the unopened cochlea of living mice routinely and reliably. PMID- 27259942 TI - Method for Dissecting the Auditory Epithelium (Basilar Papilla) in Developing Chick Embryos. AB - Chickens are an invaluable model for exploring auditory physiology. Similar to humans, the chicken inner ear is morphologically and functionally close to maturity at the time of hatching. In contrast, chicks can regenerate hearing, an ability lost in all mammals, including humans. The extensive morphological, physiological, behavioral, and pharmacological data available, regarding normal development in the chicken auditory system, has driven the progress of the field. The basilar papilla is an attractive model system to study the developmental mechanisms of hearing. Here, we describe the dissection technique for isolating the basilar papilla in developing chick inner ear. We also provide detailed examples of physiological (patch clamping) experiments using this preparation. PMID- 27259943 TI - Whole-Cell Patch-Clamp Recording of Mouse and Rat Inner Hair Cells in the Intact Organ of Corti. AB - Whole-cell patch clamping is a widely applied method to record currents across the entire membrane of a cell. This protocol describes application of this method to record currents from the sensory inner hair cells in the intact auditory sensory epithelium, the organ of Corti, isolated from rats or mice. This protocol particularly outlines the basic equipment required, provides instructions for the preparation of solutions and small equipment items, and methodology for recording voltage-activated and evoked synaptic currents from the inner hair cells. PMID- 27259944 TI - Glass Probe Stimulation of Hair Cell Stereocilia. AB - Hair cells are designed to sense mechanical stimuli of sound using their apical stereocilia hair bundles. Mechanical deflection of this hair bundle is converted into an electrical signal through gating of mechano-electric transduction channels. Stiff probe stimulation of hair bundles is an invaluable tool for studying the transduction channel and its associated processes because of the speed and ability to precisely control hair bundle position. Proper construction of these devices is critical to their ultimate performance as is appropriate placement of the probe onto the hair bundle. Here we describe the construction and use of a glass probe coupled to a piezo-electric actuator for stimulating hair bundles, including the basic technique for positioning of the stimulating probe onto the hair bundle. These piezo-electric stimulators can be adapted to other mechanically sensitive systems. PMID- 27259945 TI - A Walkthrough of Nonlinear Capacitance Measurement of Outer Hair Cells. AB - Nonlinear capacitance (NLC) measures are often used as surrogate measures of outer hair cell (OHC) electromotility (eM), since the two are commonly thought to share many biophysical features. The measurement of NLC is simpler than direct measurements of eM and, therefore, many investigators have adopted it. A standard patch-clamp hardware configuration is sufficient for recording NLC, given the proper software interface. Thus, the approach is cost effective. We use the software jClamp since it is tailored to capacitance measurement. Here we detail steps that we use to measure NLC. The walk through includes isolation of guinea pig OHCs, building voltage commands, recording, and analysis. PMID- 27259946 TI - In Vitro Functional Assessment of Adult Spiral Ganglion Neurons (SGNs). AB - Spiral ganglion neurons (SGNs) faithfully encode acoustic waves from hair cells to the cochlear nucleus (CN) using voltage-dependent ion channels. A sizable portion of our knowledge on SGN functions have been derived from pre-hearing neurons. In post-hearing SGNs, the mechanisms of how they encode the massive sound information without delay and precisely are largely unknown. Mature SGNs are housed in the central bony labyrinth of the cochlea, protected by a well insulated myelin sheath, making it a technical feat to isolate viable neurons for rigorous functional electrophysiology. Recently, we have overcome the previous intractable hindrance in SGN functional analyses. We provide a step-by-step user friendly protocol with practical applications, including patch-clamp recordings and imaging by using cultured SGNs. PMID- 27259947 TI - Mapping Auditory Synaptic Circuits with Photostimulation of Caged Glutamate. AB - Photostimulation of neurons with caged glutamate is a viable tool for mapping the strength and spatial distribution of synaptic networks in living brain slices. In photostimulation experiments, synaptic connectivity is assessed by eliciting action potentials in putative presynaptic neurons via focal photolysis of caged glutamate, while measuring postsynaptic responses via intracellular recordings. Two approaches are commonly used for delivering light to small, defined areas in the slice preparation; an optical fiber-based method and a laser-scanning-based method. In this chapter, we outline the technical bases for using photostimulation of caged glutamate to map synaptic circuits, and discuss the advantages and disadvantages of using fiber-based vs. laser-based systems. PMID- 27259948 TI - Protective effect of etanercept, an inhibitor of tumor necrosis factor-alpha, in a rat model of retinal ischemia. AB - BACKGROUND: To assess the neuroprotective effect of etanercept (Enbrel(r)) which is a commercialized Tumor necrosis factor-alpha (TNF-alpha) inhibitor on axonal injury in an animal model of acute ischemia. METHODS: Acute ischemia was induced by intraocular pressure elevation in 36 rats. The treatment groups underwent subcutaneous injection of etanercept (0.3 or 1.0 mg/kg) three times per week up to 4 weeks. The control groups were treated in the same manner using the same volume of phosphate-buffered saline (PBS). Optic nerve damage was evaluated by counting the number of axons under a transmission electron microscope. Microglial cell activity was assessed using Iba1 and CD68. RESULTS: After induction of ischemia, the ratio of preserved axons was significantly greater in the 2-week 1.0-mg/kg etanercept-treated group than in the PBS-treated group (p = 0.062). The 4-week 0.3-mg/kg and 1.0-mg/kg etanercept-treated groups also showed significantly higher ratios of preserved axons than did the PBS-treated group (p = 0.021 and 0.003, respectively). The expression of Iba1 and CD68 in the optic nerve was lower in the etanercept-treated groups than in the PBS-treated groups. Immunohistochemical staining using rabbit anti-Iba1 antibody showed that the amount of microglia at the optic nerve head was noticeably lower in the etanercept-treated groups than in the PBS-treated groups. CONCLUSIONS: Etanercept significantly suppressed optic nerve injury in this rat model of acute ischemia. This in vivo study suggests that etanercept might be a novel neuroprotective treatment agent for TNF-alpha-related disease. PMID- 27259949 TI - Assessment of human thermal perception in the hot-humid climate of Dar es Salaam, Tanzania. AB - Dar es Salaam, Tanzania, is a typical African city along the Indian Ocean coast, and therefore an important urban area to examine human thermal perception in the hot-humid tropical climate. Earlier research on human bioclimate at Dar es Salaam indicated that heat stress prevails during the hot season from October to March, peaking between December and February, particularly the early afternoons. In order to assess the human thermal perception and adaptation, two popular places, one at an urban park and another at a beach environment, were selected and questionnaire surveys were conducted in August-September 2013 and January 2014, concurrently with local micro-meteorological measurements at survey locations. The thermal conditions were quantified in terms of the thermal index of the physiologically equivalent temperature (PET) using the micro-scale climate model RayMan. The thermal comfort range of human thermal comfort and the local thermal adaptive capacity were determined in respect to the thermal index by binning thermal sensation votes. The thermal comfort range was found to be well above that in temperate climates at about 23-31 degrees C of PET. The study could significantly contribute to urban planning in Dar es Salaam and other coastal cities in the tropics. PMID- 27259951 TI - Database whiplash, crowdsourcing, and FungiDB. PMID- 27259950 TI - Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection. AB - BACKGROUND: Colonization of the airways with potential pathogenic bacteria is observed in a number of chronic respiratory diseases, such as COPD or cystic fibrosis. Infections with respiratory viruses are known triggers of exacerbations of these diseases. We here investigated if pre-exposure to bacteria alters the response of lung epithelial cells to subsequent viral infection. METHODS: Bronchial epithelial cells (BEAS-2B cells and primary bronchial epithelial cells) were exposed to heat-inactivated Haemophilus influenzae, Pseudomonas aeruginosa or Streptococcus pneumoniae and subsequently infected with respiratory syncytial virus (RSV), type 2 human adenovirus or influenza B. Levels of pro-inflammatory cytokines, viral replication and expression of pattern recognition receptors were determined in culture supernatants and/or cell lysates. RESULTS: Exposure of BEAS 2B cells to H. influenzae before and during RSV-infection synergistically increased the release of IL-6 (increase above calculated additive effect at 72 h: 56 % +/- 3 %, mean +/- SEM) and IL-8 (53 % +/- 12 %). This effect was sustained even when bacteria were washed away before viral infection and was neither associated with enhanced viral replication, nor linked to increased expression of key pattern recognition receptors. P. aeruginosa enhanced the release of inflammatory cytokines to a similar extent, yet only if bacteria were also present during viral infection. S. pneumoniae did not enhance RSV-induced cytokine release. Surprisingly, adenovirus infection significantly reduced IL-6 release in cells exposed to either of the three tested bacterial strains by on average more than 50 %. Infection with influenza B on the other hand did not affect cytokine production in BEAS-2B cells exposed to the different bacterial strains. CONCLUSION: Pre-exposure of epithelial cells to bacteria alters the response to subsequent viral infection depending on the types of pathogen involved. These findings highlight the complexity of microbiome interactions in the airways, possibly contributing to the susceptibility to exacerbations and the natural course of airway diseases. PMID- 27259952 TI - Impact of Storage Temperature on the Expression of Cell Survival Genes in Cultured ARPE-19 Cells. AB - PURPOSE: The development of a suitable storage method for retinal pigment epithelium (RPE) is necessary in the establishment of future RPE replacement therapy, and storage temperature has proven to be pivotal for cell survival. ARPE 19, a widely used model for RPE, has been shown to yield the greatest number of viable cells when stored at 16 degrees C compared to other storage temperatures. In this study, we analyze the gene expression profile of cultured ARPE-19 cells after seven days of storage at different temperatures in an effort to predict the gene-level consequences of storage of RPE transplants. MATERIALS AND METHODS: ARPE-19 cells were cultured until confluence and then stored in minimum essential medium at 4 degrees C, 16 degrees C, and 37 degrees C for seven days. The total RNA was isolated and the gene expression profile was determined using DNA microarrays. The Results were validated using qPCR. RESULTS: Principal component and hierarchical clustering analyses show that the gene expression profiles of cell cultures stored at different temperatures cluster into separate groups. Cultures stored at 4 degrees C cluster closest to the control cultures that were not stored and display the least change in gene expression after storage (157 differentially expressed genes). Cultures stored at 16 degrees C and 37 degrees C display a much larger change in differential gene expression (1787 and 1357 differentially expressed genes, respectively). At 16 degrees C, the expression of several genes with proposed tumor suppressor functions was markedly increased. Changes in regulation of several known signaling pathways and of oxidative stress markers were discovered at both 16 degrees C and 37 degrees C, and activation of the angiogenesis marker vascular endothelial growth factor (VEGF) was discovered at 37 degrees C. There was no evidence of the activation of inflammatory processes in stored cell cultures. CONCLUSION: ARPE-19 cultures stored at 16 degrees C show the greatest propensity to modulate their gene expression profile in a manner that supports cell survival during storage. PMID- 27259953 TI - Bioenergy and bioproducts from municipal organic waste as alternative to landfilling: a comparative life cycle assessment with prospective application to Mexico. AB - A life cycle assessment (LCA) of a four-stage biorefinery concept, coined H-M-Z S, that converts 1 t of organic fraction of municipal solid waste (OFMSW) into bioenergy and bioproducts was performed in order to determine whether it could be an alternative to common disposal of OFMSW in landfills in the Mexican reality. The OFMSW is first fermented for hydrogen production, then the fermentates are distributed 40 % to the methane production, 40 % to enzyme production, and 20 % to the saccharification stage. From hydrogen and methane, up to 267 MJ and 204 kWh of gross heat and electricity were produced. The biorefinery proved to be self-sustainable in terms of power (95 kWh net power), but it presented a deficit of energy for heating services (-155 MJ), which was partially alleviated by digesting the wastes from the bioproducts stages (-84 MJ). Compared to landfill, biorefinery showed lower environmental impacts in global warming (down to -128 kg CO2-eq), ozone layer depletion (2.96 * 10-6 kg CFC11-eq), and photochemical oxidation potentials (0.011 kg C2H4-eq). The landfarming of the digestates increased significantly the eutrophication impacts, up to 20 % below the eutrophication from landfilling (1.425 kg PO4-eq). These results suggest that H-M Z-S biorefinery could be an attractive alternative compared to conventional landfilling for the management of municipal solid wastes, although new alternatives and uses of co-products and wastes should be explored and tested. Moreover, the biorefinery system would benefit from the integration into the market chain of the bioproducts, i.e., enzymes and hydrolysates among others. PMID- 27259954 TI - Distribution, fate, and risk assessment of antibiotics in five wastewater treatment plants in Shanghai, China. AB - The project studied the occurrence, fate, and seasonal variation of 14 antibiotics, from five wastewater treatment plants (WWTPs) in Shanghai. The results indicated that ofloxacin, sulfamethoxazole, and oxytetracycline were the predominant antibiotics, with maximum concentrations of 1208.20, 959.13, and 564.30 ng/L in influents, while 916.88, 106.60, and 337.81 ng/L in effluents, respectively. The level of antibiotics in WWTPs obviously varied with seasonal changes, and higher detectable frequencies and concentrations were found in winter. The daily mass loads per capita of amoxicillin, enrofloxacin, and oxytetracycline in the study were all higher than those in other regions/countries, such as Hong Kong, Australia, and Italy. The elimination of antibiotics through these WWTPs was incomplete, and a wide range of removal efficiencies during the different treatment process and seasons were observed ( 500.56 to 100 % in winter and -124.24 to 94.21 % in summer). Sulfonamides were relatively easy to be removed in WWTPs and the ultraviolet (UV) process can effectively improve the removal efficiency. Risk assessment of antibiotics in effluents was estimated. Only AMOX's hazard quotient (HQ) was higher than 0.01. Even though the environmental risks in the study were estimated to be low, the potential negative effects on aquatic ecosystems should call our attention as continually discharge in the long term. PMID- 27259955 TI - Assessment of the individual and mixture toxicity of cadmium, copper and oxytetracycline, on the embryo-larval development of the sea urchin Paracentrotus lividus. AB - Multiple pollutions by trace metals and pharmaceuticals have become one of the most important problems in marine coastal areas because of its excessive toxicity on organisms living in this area. This study aimed to assess the individual and mixture toxicity of Cu, Cd, and oxytetracycline frequently existing in the contaminated marine areas and the embryo-larval development of the sea urchin Paracentrotus lividus. The individual contamination of the spermatozoid for 1 h with the increasing concentrations of Cd, Cu, and OTC decreases the fertility rate and increases larvae anomalies in the order Cu > Cd > OTC. Moreover, the normal larva frequency and the length of spicules were more sensitive than the fertilization rate and normal gastrula frequency endpoints. The mixture toxicity assessed by multiple experimental designs showed clearly that concentrations of Cd, Cu, and OTC superior to 338 MUg/L, 0.56 MUg/L, and 0.83 mg/L, respectively, cause significant larva malformations. PMID- 27259956 TI - Integrated spatial health assessment of yellow perch (Perca flavescens) populations from the St. Lawrence River, Quebec, Canada) part A: physiological parameters and pathogen assessment. AB - A multi-disciplinary approach was used to evaluate the health of yellow perch (Perca flavescens) in the St. Lawrence River (Quebec, Canada), which is experiencing a severe population decline in the downstream portion of the river. Physiological parameters, liver alterations, trace metal concentrations, parasite prevalence and abundance, stable isotope composition, and the presence/absence of the viral hemorragic septicemia virus (VHSV) were evaluated in perch collected at six sites along the river: Lake St. Francois, Lake St. Louis (north and south), Beauregard Island, and Lake St. Pierre (north and south). Trace metal concentrations in surface water were higher in Lake St. Louis and downstream of a major urban wastewater treatment plant discharge, indicating that this effluent was a significant source of Cu, As, Ag, Zn, and Cd. Levels of Pb in surface water exceeded thresholds for the protection of aquatic life in Lake St. Louis and were negatively correlated with body condition index in this lake. In Lake St. Pierre, Cu, Ag, and Cd bioaccumulated significantly in perch liver and lower body condition index and greater liver damage were observed compared to upstream sites. Parasite analyses indicated a higher abundance of metacercariae of the trematodes Apophallus brevis and Diplostomum spp. in Lake St. Louis, and VHSV was not detected in the liver of yellow perch for all studied sites. Overall, results suggested that the global health of yellow perch from Lake St. Pierre is lower compared to upstream studied sites, which could contribute to the documented population collapse at this site. PMID- 27259957 TI - Exploitation of subabul stem lignin as a matrix in controlled release agrochemical nanoformulations: a case study with herbicide diuron. AB - The utilization of nanomaterials in the domain of agriculture is at an inception, especially in the development of controlled release agrochemical nanoformulations. The present study demonstrated the potential of subabul stem lignin as a matrix material in agrochemical formulations using nanotechnology. In this study, "nanoprecipitation" method was employed and "optimized" to fabricate a stable herbicide, "diuron nanoformulation" (DNF). "Optimized DNF" (ODNF) has 5.17 +/- 0.49 % diuron loading efficiency (DLE) and 74.3 +/- 4 % encapsulation efficiency (EE). The size of nanoparticles in ODNF was 166 +/- 68 nm as revealed by FESEM/TEM studies. Physicochemical characterization of ODNF by UV, FT-IR, and DSC studies revealed the successful loading of diuron within the lignin matrix. The ODNF exhibited nonlinear biphasic release profile for diuron. Further, the bioefficacy of diuron released from ODNF was tested using canola (Brassica rapa). B. rapa seedlings grown in the soil supplemented with ODNF showed early signs of leaf chlorosis and mortality when compared with seedlings grown in the presence of commercial diuron formulation (CDF) or bulk diuron (BD), respectively. This study not only revealed the exploitation of subabul stem lignin as a "matrix" in the controlled release nanoformulation of diuron but also opened up new avenues for utilizing it as matrix for several other agrochemicals associated with the growth and development of the plant. PMID- 27259958 TI - Impact of molybdenum nanoparticles on survival, activity of enzymes, and chemical elements in Eisenia fetida using test on artificial substrata. AB - The influence of molybdenum oxide nanoparticles (MoO3) on the growth and survival of Eisenia fetida was established. The activity of antioxidant enzymes and changes in concentration of molybdenum in the body of E. fetida were determined. The degree of bacterial bioluminescence inhibition in extracts of substrates and worm was studied using luminescent strain Escherichia coli K12 TG1. The enzymatic activity of substrates before and after exposure with nanoparticles and worms was assessed. Nanoparticles have concentrations of 10, 40, and 500 mg/kg of dry matter, and substrata are made of artificial soil (substrate A) and microcrystalline cellulose (substrate B). Spherical nanoparticles MoO3, yellow in color, with size 92 +/- 0.3 nm, Z-potential 42 +/- 0.52 mV, molybdenum content 99.8 mass/%, and specific area 12 m(2)/g were used in the study. A significant decrease by 23.3 % in weight was registered (for MoO3 NPs at 500 mg/kg) on substrate A (p <= 0.05). On substrate B, the maximum decrease in weight by 20.5, 33.3, and 16.9 % (p <= 0.05) was registered at a dose of 10, 40, and 500 mg/kg, respectively; mortality was from 6.6 to 73 %. After the assessment of bacterial bioluminescence inhibition in substrates A and B (extracts) and before worms were put, the toxicity of substrates was established at doses of 40 and 500 mg/kg, expressed in inhibitory concentration (IC) 30 and IC 50 values. Comparatively, on days 7 and 14, after exposure in the presence of E. fetida, no inhibition of bioluminescence was registered in extracts of substrates A and B, indicating the reduction in toxicity of substrates. The initial content of molybdenum in E. fetida was 0.9 +/- 0.018 mg/kg of dry matter. The degree of molybdenum accumulation in worm tissue was dependent on the dose and substrate quality. In particular, 2-7 mg/kg of molybdenum accumulated from substrate A, while up to 15 kg/kg of molybdenum accumulated from substrate B (day 7). Molybdenum concentration decreased by 64.8 and 57.4 % at doses 40 and 500 mg/kg, respectively, on day 14. The reaction of antioxidant enzymes was shown in an insignificant increase of glutathione reductase (GSR) and catalase (CAT) at concentrations of 10 and 40 mg/kg in substrate A, followed by the subsequent reduction of their activity at the dose of 500 mg/kg MoO3. The activity of GSR in substrate B against the presence of MoO3 nanoparticles decreased, with significant difference of 33.5 % (p <= 0.05) at the dose of 500 mg/kg compared with untreated soil. In experiments with substrate A, an increase of catalase activity was registered for the control sample. The presence of MoO3 nanoparticles at the concentration of 10 mg/kg in the environment promoted enzymatic activity on days 7 and 14, respectively. A further increase of nanoparticle concentration resulted in the decrease of catalase activity with a minimum value at the concentration of MoO3 of 500 mg/kg. In the experiment with substrate B at the concentration of MoO3 nanoparticles of 40 mg/kg, enzymatic activity increases on day 7 of exposure. However, the stimulating effect of nanoparticles stops by day 14 of the experiment and further catalase activity is dose dependent with the smallest value in the experiment with MoO3 having the concentration of 500 mg/kg. PMID- 27259959 TI - Bioavailability of pollutants sets risk of exposure to biota and human population in reservoirs from Iguacu River (Southern Brazil). AB - The Iguacu River, located at the Southern part of Brazil, has a great socioeconomic and environmental importance due to its high endemic fish fauna and its potential to generate hydroelectric power. However, Iguacu River suffers intense discharge of pollutants in the origin of the river. In a previous report, the local environmental agency described water quality to improve along the river course. However, no study with integrated evaluation of chemical analysis and biological responses has been reported so far for the Iguacu River. In the current study, three different Brazilian fish species (Astyanax bifasciatus, Chrenicicla iguassuensis, and Geophagus brasiliensis) were captured in the five cascading reservoirs of Iguacu River for a multi-biomarker study. Chemical analysis in water, sediment, and muscle indicated high levels of bioavailable metals in all reservoirs. Polycyclic aromatic hydrocarbons (PAHs) were detected in the bile of the three fish species. Integration of the data through a FA/PCA analysis demonstrated the poorest environmental quality of the reservoir farthest from river's source, which is the opposite of what has been reported by the environmental agency. The presence of hazardous chemicals in the five reservoirs of Iguacu River, their bioaccumulation in the muscle of fish, and the biological responses showed the impacts of human activities to this area and did not confirm a gradient of pollution between the five reservoirs, from the source toward Iguacu River's mouth. Therefore, diffuse source of pollutants present along the river course are increasing the risk of exposure to biota and human populations. PMID- 27259961 TI - An improved biofilter to control the dissolved organic nitrogen concentration during drinking water treatment. AB - Dissolved organic nitrogen (DON) is a key precursor of numerous disinfection by products (DBPs), especially nitrogenous DBPs (N-DBPs) formed during disinfection in drinking water treatment. To effectively control DBPs, reduction of the DON concentration before the disinfection process is critical. Traditional biofilters can increase the DON concentration in the effluent, so an improved biofilter is needed. In this study, an improved biofilter was set up with two-layer columns using activated carbon and quartz sand under different influent patterns. Compared with the single-layer filter, the two-layer biofilter controlled the DON concentration more efficiently. The two-point influent biofilter controlled the DON concentration more effectively than the single-point influent biofilter. The improved biofilter resulted in an environment (including matrix, DO, and pH) suitable for microbial growth. Along the depth of the biofilter column, the environment affected the microbial biomass and microbial activity and thus affected the DON concentration. PMID- 27259960 TI - Surfactant enhanced pyrene degradation in the rhizosphere of tall fescue (Festuca arundinacea). AB - The present study was conducted to evaluate the effect of two non ionic surfactants (Tween 80 and Triton X-100), a biosurfactant (Lecithin), and randomly methylated-beta-cyclodextrins (RAMEB) on the remediation of pyrene from soil planted with tall fescue (Festuca arundinacea). Soils with pyrene concentration of about 243 mg kg(-1) was grown with tall fescue and were individually amended with 0, 200, 600, 1000, and 1500 mg kg(-1) of Tween 80, Triton X-100, biosurfactant, and RAMEB. The results show that all surfactants significantly increased plant biomass compared to unamended soil. Dehydrogenase activity was also stimulated as a result of surfactant addition. Only 3.9 and 3.2 % of pyrene was decreased in the uncovered and covered abiotic sterile control, suggesting that microbial degradation was the main removal mechanism of pyrene from soil. In the planted treatment receiving no surfactant, the remediation of pyrene was 45 % which is significantly higher than that of corresponding unplanted control soil, suggesting that the cultivation of tall fescue alone could enhance the overall remediation of pyrene in soil. All surfactants had significantly higher rates of pyrene remediation compared to the unamended planted soil. Generally, RAMEB displayed the highest remediation rates, i.e., 64.4-79.1 % followed by the Triton X-100, i.e., 60.1-74.8 %. The positive impact of surfactants on pyrene remediation could possibly be because of their capacities to increase its bioavailability in soil. The evidence from this study suggests that the addition of surfactants could enhance phytoremediation of PAHs polluted soil. PMID- 27259962 TI - Insight into visible light-driven photocatalytic degradation of diesel oil by doped TiO2-PS floating composites. AB - TiO2-pearlstone (PS) floatable photocatalysts were synthesized using a facile sol gel method and confirmed by XRD, N2 adsorption-desorption, SEM, EDX, TEM, FT-IR, XPS, and UV-vis DRS measurements. It has been found that the photocatalysts composed of anatase TiO2 deposited on the surface of PS and formed mesoporous structure. By N or B/N doping, the band gap of the photocatalyst has been narrowed. The obtained floatable photocatalysts can be applied to solar light driven remediation of oil-contaminated water. Diesel oil was chosen as the model pollutant to evaluate the photocatalytic activity. The results showed B/N-TiO2-PS exhibited the highest photocatalytic activity for diesel oil under visible light irradiation, which is 48 % removal rate for 9 h. The reaction rate constant k of B/N-TiO2-PS is 0.08423 h(-1), which is four times larger than that of pure TiO2 PS. Moreover, the characteristic of floatable makes the photocatalysts easier to separate and reuse, which showed great potential for practical applications in the field of environmental cleanup and solar energy conversion. PMID- 27259963 TI - Microbial disinfection of water with endotoxin degradation by photocatalysis using Ag@TiO2 core shell nanoparticles. AB - The studies on photocatalytic disinfection of water contaminated with Escherichia coli using Ag core and TiO2 shell (Ag@TiO2) nanoparticles under UV irradiation showed that these nanoparticles are very efficient in water disinfection both in their free and immobilised form. Complete disinfection of 40 * 10(8) CFU/mL could be achieved in 60 min with 0.4 g/L catalyst loading and in 35 min with 1 g/L catalyst loading. Ag@TiO2 nanoparticles were found to be superior to TiO2 nanoparticles in photocatalytic disinfection of water. Kinetics of disinfection followed Chick's law, and the pseudo-first-order rate constant was 0.0168 min(-1) for a catalyst loading of 0.1 g/L. Disinfection of water and degradation of endotoxins (harmful disinfection residual) occurred simultaneously during photocatalysis thereby making the treated water safe for use. Endotoxin degradation showed a shifting order of kinetics. The rate of photocatalysis with nanoparticles immobilised in cellulose acetate film was marginally lower as compared to that of free nanoparticles. Negligible Ag ion leakage and re-growth of cells post-photo-catalytic treatment of water confirmed that complete disintegration of E. coli occurred during photocatalysis making the treated water safe for use. Therefore, Ag@TiO2 nanoparticles have a potential for large-scale application in drinking water treatment plants and household purification units. PMID- 27259965 TI - Developing consensus for postgraduate global health electives: definitions, pre departure training and post-return debriefing. AB - BACKGROUND: Global health (GH) electives are on the rise, but with little consensus on the need or content of pre-departure training (PDT) or post-return debriefing (PRD) for electives in postgraduate medical education. METHODS: Using a 2-iteration Delphi process to encourage discussion and consensus, participants from 14 medical schools across Canada provided input to promote more uniform policy towards defining GH electives, when PDT and PRD should be mandatory and what curriculum should be included. RESULTS: There is consensus that PDT and PRD should be mandatory for international electives. Respondents felt that PDT should include a broad range of topics including objectives, travel safety, personal health, logistics, ethics of GH, scope of practice/supervision, and cultural awareness. PRD should include elective evaluation, lessons learned, knowledge translation, review of health and safety, and issues of reintegration. The format of PDT and PRD needs to be individualized to each institution to fit within the limitations of faculty who can serve as facilitators. Global health educators agreed on the importance of mandatory PDT and PRD for remote Canadian aboriginal electives, but did not feel that they could make recommendations without additional input of aboriginal scholars. CONCLUSIONS: All residency programs that send residents on international electives should work towards instituting quality, mandatory PDT and PRD. PDT and PRD should be recognized by universities as having academic merit and by program directors as core resident learning activities. Curriculum and objectives could be arranged around CanMEDS competencies, a physician competency framework that emphasizes qualities beyond medical expert such as professionalism, health advocate, and collaborator. PMID- 27259964 TI - Cultivating Chlorella vulgaris and Scenedesmus quadricauda microalgae to degrade inorganic compounds and pesticides in water. AB - This work evaluates the possibility of cultivating Scenedesmus quadricauda and Chlorella vulgaris microalgae in wastewater from the hydroponic cultivation of tomatoes with the aim of purifying the water. S. quadricauda and C. vulgaris were also used in purification tests carried out on water contaminated by the following active ingredients: metalaxyl, pyrimethanil, fenhexamid, iprodione, and triclopyr. Fifty-six days after the inoculum was placed, a reduction was found in the concentration of nitric nitrogen, ammonia nitrogen, and soluble and total phosphorus. The decrease was 99, 83, 94, and 94 %, respectively, for C. vulgaris and 99, 5, 88, and 89 %, respectively, for S. quadricauda. When the microalgae were present, all the agrochemicals tested were removed more quickly from the water than from the sterile control (BG11). The increase in the rate of degradation was in the order metalaxyl > fenhexamid > iprodione > triclopyr > pyrimethanil. It was demonstrated that there was a real degradation of fenhexamid, metalaxyl, triclopyr, and iprodione, while in the case of pyrimethanil, the active ingredient removed from the substrate was absorbed onto the cells of the microalgae. It was also found that the agrochemicals used in the tests had no significant effect on the growth of the two microalgae. The experiment highlighted the possibility of using cultivations of C. vulgaris and S. quadricauda as purification systems for agricultural wastewater which contains eutrophic inorganic compounds such as nitrates and phosphates and also different types of pesticides. PMID- 27259966 TI - [Not Available]. PMID- 27259967 TI - Treatment of lip florid papillomatosis with topical ALA-PDT combined with curettage: Outcome and safety. AB - BACKGROUND: Photodynamic therapy (PDT) is a successful treatment in clinical practice. PDT is increasingly used to cure the patients with skin cancer, especially in the elder. The purpose of this study was to evaluate the treatment outcome and safety of PDT with aminolevulinic acid (5-ALA) combined with surgical curettage for lip florid papillomatosis. METHODS: In this study, 4 cases of lip florid papillomatosis were treated with topical aminolevulinic acid photodynamic therapy (ALA-PDT) combined with curettage. First, the warts were removed with the patient under local anesthesia. The depth of the ablation and curettage reached the dermal layer. Then, the first session of PDT was performed after 2days. Ten percent 5-ALA cream was applied to lesional skin with occlusive dressing for a 3 h incubation period and the lesions of warts were irradiated for 10min by using a 635-nm laser beam of 177mW/cm2 intensity. The ALA-PDT was repeated after 1 and 3 weeks and two other treatments applied if necessary. Follow-up evaluation was performed at our outpatient clinic at 3 and 6 months after completion of therapy. RESULTS: After three PDT sessions following surgical curettage, 3 patients were cured at 3 months off treatment, one cases relapsed, corresponding to a recurrent rate of 25%. There was no other recurrence at 6 months off treatment. The satisfaction rate of patients was 95% at 3 month and 100% at 6 months after treatment. CONCLUSIONS: The combined treatment of topical ALA-PDT and curettage was proven to be safe and effective in lip florid papillomatosis. PMID- 27259968 TI - Speckled lentiginous nevus syndrome. PMID- 27259969 TI - Microalbuminuria in Children With Primary Hypertension. PMID- 27259970 TI - Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial. AB - BACKGROUND: Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. METHODS: After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. RESULTS: All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 +/- 129 pg/mL before treatment and 241 +/- 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 +/- 109 pg/mL before treatment, and 168 +/ 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite the evident macroscopic damage induced by naproxen. CONCLUSION: Rebamipide does not protect against naproxen-induced gastric damage in healthy volunteers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02632812 . Registered 14 December 2015. PMID- 27259972 TI - Synthesis and Photophysical Properties of Novel Donor-Acceptor N-(Pyridin-2-yl) Substituted Benzo(thio)amides and Their Difluoroboranyl Derivatives. AB - The unprecedented N-pyridin-2-yl substituted benzo(thio)amides were prepared and subsequently converted into the cyclic difluoroboranyl (BF2) derivatives. Mass spectrometry, multinuclear NMR, IR, and elemental analysis confirmed the structure of these compounds. UV/vis and fluorescence spectroscopy as well as first-principle calculations were used to study their properties. For the first time, the influence of both the O/S replacement and presence/absence of the BF2 moiety on the photophysical properties of compounds exhibiting charge transfer properties were examined experimentally and theoretically. We show that the sulfur-containing compound has a much smaller emission quantum yield than its oxygen counterpart. The fluorescence quantum yield is much higher upon formation of the difluoroboranyl complex. PMID- 27259971 TI - Transcriptome sequences spanning key developmental states as a resource for the study of the cestode Schistocephalus solidus, a threespine stickleback parasite. AB - BACKGROUND: Schistocephalus solidus is a well-established model organism for studying the complex life cycle of cestodes and the mechanisms underlying host parasite interactions. However, very few large-scale genetic resources for this species are available. We have sequenced and de novo-assembled the transcriptome of S. solidus using tissues from whole worms at three key developmental states - non-infective plerocercoid, infective plerocercoid and adult plerocercoid - to provide a resource for studying the evolution of complex life cycles and, more specifically, how parasites modulate their interactions with their hosts during development. FINDINGS: The de novo transcriptome assembly reconstructed the coding sequence of 10,285 high-confidence unigenes from which 24,765 non redundant transcripts were derived. 7,920 (77 %) of these unigenes were annotated with a protein name and 7,323 (71 %) were assigned at least one Gene Ontology term. Our raw transcriptome assembly (unfiltered transcripts) covers 92 % of the predicted transcriptome derived from the S. solidus draft genome assembly currently available on WormBase. It also provides new ecological information and orthology relationships to further annotate the current WormBase transcriptome and genome. CONCLUSION: This large-scale transcriptomic dataset provides a foundation for studies on how parasitic species with complex life cycles modulate their response to changes in biotic and abiotic conditions experienced inside their various hosts, which is a fundamental objective of parasitology. Furthermore, this resource will help in the validation of the S solidus gene features that have been predicted based on genomic sequence. PMID- 27259973 TI - Accounting for heterogeneity in meta-analysis using a multiplicative model-an empirical study. AB - In meta-analysis, the random-effects model is often used to account for heterogeneity. The model assumes that heterogeneity has an additive effect on the variance of effect sizes. An alternative model, which assumes multiplicative heterogeneity, has been little used in the medical statistics community, but is widely used by particle physicists. In this paper, we compare the two models using a random sample of 448 meta-analyses drawn from the Cochrane Database of Systematic Reviews. In general, differences in goodness of fit are modest. The multiplicative model tends to give results that are closer to the null, with a narrower confidence interval. Both approaches make different assumptions about the outcome of the meta-analysis. In our opinion, the selection of the more appropriate model will often be guided by whether the multiplicative model's assumption of a single effect size is plausible. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27259977 TI - Patient-Reported Outcomes in Glomerular Disease. AB - Incorporation of the patient perspective into research and clinical practice will enrich our understanding of the status and management of patients with glomerular disease and may result in therapies that better address patient needs. In recent years, the importance of the patient experience of glomerular disease has become clear, and significant efforts have been undertaken to systematically capture and describe the patient's disease experience. Patient-reported outcome instruments provide a means to assess the patient's experience in a quantitative manner, thus enabling for comparisons within and between patients. Patient-reported outcome assessments are solely on the basis of a patient report about the status of their health without amendment or interpretation by a clinician or others. Patient reported outcome assessments provide an opportunity to incorporate the patient perspective into clinical care, research, and clinical trials. Our paper provides an overview of terminology and development methods for patient-reported outcomes and reviews (1) currently available patient-reported outcome instruments appropriate for use in glomerular disease, (2) existing patient-reported outcome data in glomerular disease, and (3) opportunities for incorporating patient reported outcome instruments into clinical care and research. PMID- 27259978 TI - Unresolved questions regarding human hereditary deafness. AB - Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. This review on hereditary deafness focuses on three examples considered at first glance to be uncomplicated, however, upon inspection, are enigmatic and ripe for future research efforts. The three examples of clinical and genetic complexities are drawn from studies of (i) Pendred syndrome/DFNB4 (PDS, OMIM 274600), (ii) Perrault syndrome (deafness and infertility) due to mutations of CLPP (PRTLS3, OMIM 614129), and (iii) the unexplained extensive clinical variability associated with TBC1D24 mutations. At present, it is unknown how different mutations of TBC1D24 cause non-syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities for restoration as well as preservation of normal hearing. PMID- 27259979 TI - GATA2 regulates dendritic cell differentiation. AB - Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin(-)Sca-1(+)Kit(+) cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage specific transcription factors in DC progenitors, thereby contributing to DC differentiation. PMID- 27259981 TI - Mixed - Lineage Protein kinases (MLKs) in inflammation, metabolism, and other disease states. AB - Mixed lineage kinases, or MLKs, are members of the MAP kinase kinase kinase (MAP3K) family, which were originally identified among the activators of the major stress-dependent mitogen activated protein kinases (MAPKs), JNK and p38. During stress, the activation of JNK and p38 kinases targets several essential downstream substrates that react in a specific manner to the unique stressor and thus determine the fate of the cell in response to a particular challenge. Recently, the MLK family was identified as a specific modulator of JNK and p38 signaling in metabolic syndrome. Moreover, the MLK family of kinases appears to be involved in a very wide spectrum of disorders. This review discusses the newly identified functions of MLKs in multiple diseases including metabolic disorders, inflammation, cancer, and neurological diseases. PMID- 27259982 TI - Regulation of angiogenin expression and epithelial-mesenchymal transition by HIF 1alpha signaling in hypoxic retinal pigment epithelial cells. AB - Choroidal neovascularization (CNV) is a major cause of vision loss in many retinal diseases. Hypoxia is determined to be a key inducer of CNV and hypoxia inducible factor-1 (HIF-1) is an important transcription factor. Epithelial mesenchymal transition (EMT) and the synthesis of proangiogenic cytokines make great contributions to the development of CNV. In the present study, the role of HIF-1alpha signaling in the regulation of angiogenin (ANG) expression and EMT in hypoxic retinal pigment epithelial cells was investigated. A significant elevation expression of ANG expression level in a mouse model of laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased expression level of ANG and induction of EMT accompanied with stabilization and nucleus translocation of HIF-1alpha. Blockage of HIF-1alpha signaling resulted in inhibition of high expression of ANG and EMT features. The direct interaction between HIF-1alpha and ANG promoter region was identified by ChIP-qPCR. The association of RNase 4 mRNA level with HIF-1alpha signaling was also clarified in APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S rRNA transcription, promoted cell proliferation and tube formation in human retinal microvascular endothelial cells. In conclusion, the hypoxic conditions regulate the expression of ANG and EMT via an activation of HIF-1alpha signaling. It provides molecular evidence for potential therapy strategies of treating CNV. PMID- 27259980 TI - Immunoregulatory roles of versican proteolysis in the myeloma microenvironment. AB - Myeloma immunosurveillance remains incompletely understood. We have demonstrated proteolytic processing of the matrix proteoglycan, versican (VCAN), in myeloma tumors. Whereas intact VCAN exerts tolerogenic activities through Toll-like receptor 2 (TLR2) binding, the immunoregulatory consequences of VCAN proteolysis remain unknown. Here we show that human myeloma tumors displaying CD8(+) infiltration/aggregates underwent VCAN proteolysis at a site predicted to generate a glycosaminoglycan-bereft N-terminal fragment, versikine Myeloma associated macrophages (MAMs), rather than tumor cells, chiefly produced V1-VCAN, the precursor to versikine, whereas stromal cell-derived ADAMTS1 was the most robustly expressed VCAN-degrading protease. Purified versikine induced early expression of inflammatory cytokines interleukin 1beta (IL-1beta) and IL-6 by human myeloma marrow-derived MAMs. We show that versikine signals through pathways both dependent and independent of Tpl2 kinase, a key regulator of nuclear factor kappaB1-mediated MAPK activation in macrophages. Unlike intact VCAN, versikine-induced Il-6 production was partially independent of Tlr2. In a model of macrophage-myeloma cell crosstalk, versikine induced components of "T cell inflammation," including IRF8-dependent type I interferon transcriptional signatures and T-cell chemoattractant CCL2. Thus the interplay between stromal cells and myeloid cells in the myeloma microenvironment generates versikine, a novel bioactive damage-associated molecular pattern that may facilitate immune sensing of myeloma tumors and modulate the tolerogenic consequences of intact VCAN accumulation. Therapeutic versikine administration may potentiate T-cell activating immunotherapies. PMID- 27259984 TI - Host-feeding patterns of mosquito species in Germany. AB - BACKGROUND: Mosquito-borne pathogens are of growing importance in many countries of Europe including Germany. At the same time, the transmission cycles of most mosquito-borne pathogens (e.g. viruses or filarial parasites) are not completely understood. There is especially a lack of knowledge about the vector capacity of the different mosquito species, which is strongly influenced by their host feeding patterns. While this kind of information is important to identify the relevant vector species, e.g. to direct efficient control measures, studies about the host-feeding patterns of mosquito species in Germany are scarce and outdated. METHODS: Between 2012 and 2015, 775 blood-fed mosquito specimens were collected. Sampling was conducted with Heavy Duty Encephalitis Vector Survey traps, Biogents Sentinel traps, gravid traps, hand-held aspirators, sweep nets, and human-bait collection. The host species for each mosquito specimen was identified with polymerase chain reactions and subsequent Sanger sequencing of the cytochrome b gene. RESULTS: A total of 32 host species were identified for 23 mosquito species, covering 21 mammalian species (including humans) and eleven bird species. Three mosquito species accounted for nearly three quarters of all collected blood-fed mosquitoes: Aedes vexans (363 specimens, 46.8 % of all mosquito specimens), Culex pipiens pipiens form pipiens (100, 12.9 %) and Ochlerotatus cantans (99, 12.8 %). Non-human mammals dominated the host species (572 specimens, 73.8 % of all mosquito specimens), followed by humans (152, 19.6 %) and birds (51, 6.6 %). The most common host species were roe deer (Capreolus capreolus; 258 mosquito specimens, 33.3 % of all mosquito specimens, 65 % of all mosquito species), humans (Homo sapiens; 152, 19.6 %, 90 %), cattle (Bos taurus; 101, 13.0 %, 60 %), and wild boar (Sus scrofa; 116, 15.0 %, 50 %). There were no statistically significant differences in the spatial-temporal host-feeding patterns of the three most common mosquito species. CONCLUSIONS: Although the collected blood-fed mosquito species had a strong overlap of host species, two different host-feeding groups were identified with mosquito species feeding on (i) non-human mammals and humans or (ii) birds, non-human mammals, and humans, which make them potential vectors of pathogens only between mammals or between mammals and birds, respectively. Due to the combination of their host-feeding patterns and wide distribution in Germany, Cx. pipiens pipiens form pipiens and Cx. torrentium are potentially most important vectors for pathogens transmitted from birds to humans and the species Ae. vexans for pathogens transmitted from non-human mammals to humans. Finally, the presented study indicated a much broader host range compared to the classifications found in the literature for some of the species, which highlights the need for studies on the host-feeding patterns of mosquitoes to further assess their vector capacity and the disease ecology in Europe. PMID- 27259985 TI - Mycophenolic acid, an immunomodulator, has potent and broad-spectrum in vitro antiviral activity against pandemic, seasonal and avian influenza viruses affecting humans. AB - Immunomodulators have been shown to improve the outcome of severe pneumonia. We have previously shown that mycophenolic acid (MPA), an immunomodulator, has antiviral activity against influenza A/WSN/1933(H1N1) using a high-throughput chemical screening assay. This study further investigated the antiviral activity and mechanism of action of MPA against contemporary clinical isolates of influenza A and B viruses. The 50 % cellular cytotoxicity (CC50) of MPA in Madin Darby canine kidney cell line was over 50 uM. MPA prevented influenza virus induced cell death in the cell-protection assay, with significantly lower IC50 for influenza B virus B/411 than that of influenza A(H1N1)pdm09 virus H1/415 (0.208 vs 1.510 uM, P=0.0001). For H1/415, MPA interfered with the early stage of viral replication before protein synthesis. For B/411, MPA may also act at a later stage since MPA was active against B/411 even when added 12 h post infection. Virus-yield reduction assay showed that the replication of B/411 was completely inhibited by MPA at concentrations >=0.78 uM, while there was a dose dependent reduction of viral titer for H1/415. The antiviral effect of MPA was completely reverted by guanosine supplementation. Plaque reduction assay showed that MPA had antiviral activity against eight different clinical isolates of A(H1N1), A(H3N2), A(H7N9) and influenza B viruses (IC50 <1 uM). In summary, MPA has broad-spectrum antiviral activity against human and avian-origin influenza viruses, in addition to its immunomodulatory activity. Together with a high chemotherapeutic index, the use of MPA as an antiviral agent should be further investigated in vivo. PMID- 27259983 TI - Autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway. AB - Autophagy plays important roles in self-renewal and differentiation of stem cells. Hepatic progenitor cells (HPCs) are thought to have the ability of self renewal as well as possess a bipotential capacity, which allows them to differentiate into both hepatocytes and bile ductular cells. However, how autophagy contributes to self-renewal and differentiation of hepatic progenitor cells is not well understood. In this study, we use a well-established rat hepatic progenitor cell lines called WB-F344, which is treated with 3.75 mM sodium butyrate (SB) to promote the differentiation of WB-F344 along the biliary phenotype. We found that autophagy was decreased in the early stage of biliary differentiation, and maintained a low level at the late stage. Activation of autophagy by rapamycin or starvation suppressed the biliary differentiation of WB F344. Further study reported that autophagy inhibited Notch1 signaling pathway, which contributed to biliary differentiation and morphogenesis. In conclusions, autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway. PMID- 27259986 TI - Long-term follow-up of non-syphilitic paroxysmal cold hemoglobinuria in an adult. PMID- 27259987 TI - Klebsiella pneumoniae primary liver abscess associated with ruxolitinib. PMID- 27259988 TI - Nonossifying fibromas of the distal tibia: possible etiologic relationship to the interosseous membrane. AB - PURPOSE: Nonossifying fibromas (NOFs) present in a characteristic pattern in the distal tibia. Their predilection to this region and etiology remain imprecisely defined. METHODS: We performed a retrospective chart review of patients between January 2003 and March 2014 for distal tibial NOFs. We then reviewed radiographs (XRs), computed tomography (CT), and magnetic resonance imaging (MRI) for specific lesion characteristics. RESULTS: We identified 48 distal tibia NOFs in 47 patients (31 male, 16 female; mean age 12.3 years, range 6.9-17.8). This was the second most common location in our population (30 % of NOFs), behind the distal femur (42 %). Thirty-four lesions had CT and nine had MRI. Thirty-one percent were diagnosed by pathologic fracture. Ninety-six percent of lesions were located characteristically in the distal lateral tibia by plain radiograph, in direct communication with the distal extent of the interosseous membrane on 33 of the 34 (97 %) lesions with CT available for review and all nine (100 %) with MRI. The remaining two lesions occurred directly posterior. CONCLUSIONS: The vast majority of distal tibial NOFs occur in a distinct anatomic location at the distal extent of the interosseous membrane, which may have etiologic implications. LEVEL OF EVIDENCE: IV (case series). PMID- 27259989 TI - Protein Misfolding Cyclic Amplification Cross-Species Products of Mouse-Adapted Scrapie Strain 139A and Hamster-Adapted Scrapie Strain 263K with Brain and Muscle Tissues of Opposite Animals Generate Infectious Prions. AB - Transmission of prions between mammalian species is limited by a "species barrier," a biological effect involving an increase in incubation period to decrease the percentage of animals succumbing to disease. In this study, we used protein misfolding cyclic amplification (PMCA) technique, which accelerates the conversion of prion proteins in vitro. Direct interspecies PMCA involving 144 cycles confirmed that both mouse-adapted scrapie strain 139A and hamster-adapted 263K could use brain homogenates of opposite species to form proteinase K (PK) resistant PrP proteins (PrPres). Newly formed interspecies prions could stably propagate themselves in subsequent serial PMCA passages. The two types of PMCA generated cross-species PrPres changed their glycosylation profiles, which was similar to that observed during interspecies infection by the mouse agent 139A in vivo. These profiles were distinct from individual seeded PrPSc and possessed properties of new hosts. Comparative analysis with respect to PK resistance showed no significant diversity between PMCA-PrPres and native PrPSc or between brain and muscle PrPres. However, PrPres from the relatively early cycles of serial PMCA showed lower PK resistance than those from later cycles. Inoculation of these PMCA products amplified with homogeneous or heterogeneous brain tissues (cross-species products) induced experimental transmissible spongiform encephalopathies. These results suggested that PMCA can help prion strains to overcome species barrier and to propagate efficiently both in vitro and in vivo. PMID- 27259990 TI - Establishment and characterization of a cell line (HCH-1) originating from a human clear cell carcinoma of the ovary. AB - BACKGROUND: Cell lines are very useful for both clinical and basic research. The establishment of ovarian, malignant tumor cell lines with aggressive histology is especially important. We describe the establishment and characterization of a new human clear cell carcinoma cell line of the ovary. RESULTS: The cell line HCH-1 was established from an ovarian tumor from a 67-year-old woman. This cell line has grown well for 230 months and has been subcultured more than 50 times. Monolayer cultured cells are polygonal in shape, showing a pavement-like arrangement and a tendency to pile up without contact inhibition. It exhibits a human karyotype with a modal chromosomal number in the hypodiploid range. The cells could be transplanted into the subcutis of SCID mice and produced tumors resembling the original tumor. HCH-1 cells produced CA125 and CA19-9, also identified immunohistochemically in both the original tumor and the heterotransplanted tumors. The cells were sensitive to actinomycin D, carboplatin, cisplatin and mitomycin C, drugs commonly used in the treatment of gynecological cancers. Variant was not found in hotspot of the 50 most commonly reported oncogenes and tumor suppressor genes. Only 12 ovarian clear cell carcinoma cell lines and their characteristics have thus far been reported in the literature. HCH-1 is the first ovarian clear cell carcinoma cell line reported in which the chromosome number is in the hypodiploid range and only the second cell line in which CA125 and CA19-9 are expressed. CONCLUSIONS: Since it is impossible to establish a cell line from the malignant tumor of each patient, the cell line that we established, characterized and report in this paper may be very useful in basic research on ovarian cancer. We have much to learn about the pathogenesis of clear cell carcinoma and this extra line of enquiry may lead us to a better understanding of how to treat and cure this serious disease. PMID- 27259991 TI - Resistive indices of cerebral arteries in very preterm infants: values throughout stay in the neonatal intensive care unit and impact of patent ductus arteriosus. AB - BACKGROUND: Little is known about cerebral artery resistive index values in infants born extremely preterm. OBJECTIVE: To report resistive index values in various cerebral arteries in a prospective cohort of preterm infants born at <29 weeks' gestation, and to compare resistive index in these arteries and assess the relationship between resistive index and hemodynamically significant patent ductus arteriosus. MATERIALS AND METHODS: Using Doppler imaging, we obtained resistive index values of internal carotid arteries, basilar artery, anterior cerebral artery, and pial and striatal arteries in the first 3 days of age and weekly thereafter until discharge or death. We analyzed paired observations using the Wilcoxon signed-rank test, between-group comparisons with the Mann-Whitney test. RESULTS: We performed 771 examinations in 235 infants. Resistive indices differed among arteries: vessels with larger diameters showed significantly higher resistive indices. Resistive index in infants without patent ductus arteriosus was lower than that in infants with hemodynamically significant patent ductus arteriosus (median in anterior cerebral artery: 0.75 and 0.82, respectively; P<0.001), though this was not statistically significant in all arteries. There was no difference in pre- and post-ligation resistive indices in infants who underwent patent ductus arteriosus ligation. CONCLUSION: For accurate follow-up and comparison of cerebral artery resistive index, the same artery should be examined on each occasion. PMID- 27259993 TI - Elevated expression of RNA methyltransferase BCDIN3D predicts poor prognosis in breast cancer. AB - BACKGROUND: BCDIN3D is a member of the Bin3 methyl-transferase family that targets the 5' mono-phosphate of nucleic acids. Although BCDIN3D has been shown to increase tumorigenic phenotypes and invasiveness in MDA-MB-231 cells, its the clinical implications in breast cancer remain unclear. METHODS: We screened for BCDIN3D using tissue microarrays constructed from 250 patients who were histologically confirmed to have invasive ductal breast carcinoma at the Fudan University Shanghai Cancer Center. RESULTS: The survival analysis by Kaplan-Meier and Cox regression showed that BCDIN3D expression level served as a prognostic factor for disease-free survival (P = 0.042). The prognostic value of BCDIN3D was most significant in triple-negative breast cancer (TNBC) patients (P = 0.007). CONCLUSIONS: BCDIN3D might serve as an important prognostic factor for TNBC patients. PMID- 27259994 TI - Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2 mediated degradation of acetylated LKB1. AB - Aims-SIRT1 exerts potent activity against cellular senescence and vascular ageing. By decreasing LKB1 protein levels, it promotes the survival and regeneration of endothelial cells. The present study aims to investigate the molecular mechanisms underlying SIRT1-mediated LKB1 degradation for the prevention of vascular ageing.Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells. Site-directed mutagenesis revealed that acetylation at lysine (K) 64 of LKB1 triggers the formation of SIRT1/HERC2/LKB1 protein complex and subsequent proteasomal degradation. In vitro cellular studies suggested that accumulation of acetylated LKB1 in the nucleus leads to endothelial activation, in turn stimulating the proliferation of vascular smooth muscle cells and the production of extracellular matrix proteins. Chromatin immunoprecipitation quantitative PCR confirmed that acetylated LKB1 interacts with and activates TGFbeta1 promoter, which is inhibited by SIRT1. Knocking down either SIRT1 or HERC2 results in an increased association of LKB1 with the positive regulatory elements of TGFbeta1 promoter. In mice without endothelial nitric oxide synthase, selective overexpression of human SIRT1 in endothelium prevents hypertension and age-related adverse arterial remodeling. Lentiviral-mediated knockdown of HERC2 abolishes the beneficial effects of endothelial SIRT1 on both arterial remodeling and arterial blood pressure control.Conclusion-By downregulating acetylated LKB1 protein via HERC2, SIRT1 fine-tunes the crosstalk between endothelial and vascular smooth muscle cells to prevent adverse arterial remodeling and maintain vascular homeostasis. PMID- 27259995 TI - Biochemical and structural characterization of a DNA N6-adenine methyltransferase from Helicobacter pylori. AB - DNA N6-methyladenine modification plays an important role in regulating a variety of biological functions in bacteria. However, the mechanism of sequence-specific recognition in N6-methyladenine modification remains elusive. M1.HpyAVI, a DNA N6 adenine methyltransferase from Helicobacter pylori, shows more promiscuous substrate specificity than other enzymes. Here, we present the crystal structures of cofactor-free and AdoMet-bound structures of this enzyme, which were determined at resolutions of 3.0 A and 3.1 A, respectively. The core structure of M1.HpyAVI resembles the canonical AdoMet-dependent MTase fold, while the putative DNA binding regions considerably differ from those of the other MTases, which may account for the substrate promiscuity of this enzyme. Site-directed mutagenesis experiments identified residues D29 and E216 as crucial amino acids for cofactor binding and the methyl transfer activity of the enzyme, while P41, located in a highly flexible loop, playing a determinant role for substrate specificity. Taken together, our data revealed the structural basis underlying DNA N6-adenine methyltransferase substrate promiscuity. PMID- 27259996 TI - Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence. AB - Amniotic epithelial cells (AECs) are a class of fetal stem cells that derives from the epiblast and resides in the amnion until birth. AECs are suitable candidates for regenerative medicine because of the ease of collection, their low immunogenicity and inability to form tumors after transplantation. Even though human AECs have been widely investigated, the fact remains that very little is known about AECs isolated from rat, one of the most common animal models in medical testing. In this study, we showed that rat AECs retained stemness properties and plasticity, expressed the pluripotency markers Sox2, Nanog, and Oct4 and were able to differentiate toward the osteogenic lineage. The addition of conditioned medium collected from rat AECs to lipopolysaccharide-activated macrophages elicited anti-inflammatory properties through a decrease of Tnfa expression and slowed tumor cell proliferation in vitro and in vivo. The senescence-associated secretory phenotype was also significantly lower upon incubation of senescent human IMR-90 fibroblast cells with conditioned medium from rat AECs. These results confirm the potential of AECs in the modulation of inflammatory mechanisms and open new therapeutic possibilities for regenerative medicine and anti-aging therapies as well. PMID- 27259997 TI - The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer. AB - MET overexpression and the EGFR T790M mutation are both associated with acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). We characterized the frequency, underlying molecular mechanisms, and subsequent treatment for AR in MET overexpressing NSCLC patients with or without the T790M mutation. The study participants were 207 patients with advanced NSCLC and AR to EGFR-TKIs. The percentages of MET-, T790M- and MET/T790M-positive patients were 20.3% (42/207), 34.8% (72/207) and 6.8% (14/207), respectively. The disease control rate was 100% (5/5) for five patients with MET overexpression who received EGFR-TKIs plus a MET inhibitor. Among the MET/T790M-positive patients, seven received EGFR-TKIs plus a MET inhibitor and four received a T790M inhibitor, but no response was observed. The median post-progression survival (PPS) was 14.1, 24.5, and 10.7 months for MET-overexpressing, T790M-positive and MET/T790M-positive patients, respectively (P=0.044). c-Met, p-Met, ERBB3, and p-ERBB3 were highly expressed in MET-positive and MET/T790M-positive patients, but were poorly expressed in T790M-positive patients. EGFR, p-EGFR, AKT, p-AKT, MAPK, and p-MAPK were highly expressed in all three groups. These results suggest that MET/T790M-positive patients are at higher risk of AR to EGFR-TKIs, and have a worse PPS than patients with only MET overexpression or the T790M mutation alone. Clinical trials are needed to determine the best treatment for patients with both MET overexpression and the EGFR T790M mutation. PMID- 27259998 TI - Peroxiredoxin 1 promotes invasion and migration by regulating epithelial-to mesenchymal transition during oral carcinogenesis. AB - Tobacco smoking is the major risk factor for oral squamous cell carcinoma (OSCC). Previously, we found that nicotine up-regulates peroxiredoxin 1 (Prx1), an important antioxidant enzyme, and nuclear factor kappa B (NFkappaB) in OSCC cells. However, the molecular mechanism of Prx1 in oral carcinogenesis remains obscure. To improve our understanding of the functional role of Prx1 during the cascade of tobacco-associated oral carcinogenesis, we characterized Prx1, NFkappaB, and epithelial-to-mesenchymal transition (EMT) markers including E cadherin, vimentin and Snail in 30 primary oral tumors (15 from smokers with OSCC and 15 from non-smokers with OSCC) and 10 normal oral mucosa specimens from healthy individuals. The expression levels of Prx1, nuclear NFkappaB, vimentin and Snail were higher in the tumors from smokers with OSCC than in those from non smokers with OSCC or the healthy controls. The expression levels of E-cadherin showed an opposite trend. Prx1 silencing suppressed the nicotine-induced EMT, cell invasion and migration in SCC15 cells in vitro. Furthermore, Prx1 activated the NFkappaB pathway in SCC15 cells. Prx1 might therefore play an oncogenic role in tobacco-related OSCC and thus serve as a target for chemopreventive and therapeutic interventions. PMID- 27259999 TI - 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment. AB - Systemic inflammatory events and localized disease, mediated by the microbiome, may be measured in saliva as head and neck squamous cell carcinoma (HNSCC) diagnostic and prognostic biomonitors. We used a 16S rRNA V3-V5 marker gene approach to compare the saliva microbiome in DNA isolated from Oropharyngeal (OPSCC), Oral Cavity Squamous Cell Carcinoma (OCSCC) patients and normal epithelium controls, to characterize the HNSCC saliva microbiota and examine their abundance before and after surgical resection.The analyses identified a predominance of Firmicutes, Proteobacteria and Bacteroidetes, with less frequent presence of Actinobacteria and Fusobacteria before surgery. At lower taxonomic levels, the most abundant genera were Streptococcus, Prevotella, Haemophilus, Lactobacillus and Veillonella, with lower numbers of Citrobacter and Neisseraceae genus Kingella. HNSCC patients had a significant loss in richness and diversity of microbiota species (p<0.05) compared to the controls. Overall, the Operational Taxonomic Units network shows that the relative abundance of OTU's within genus Streptococcus, Dialister, and Veillonella can be used to discriminate tumor from control samples (p<0.05). Tumor samples lost Neisseria, Aggregatibacter (Proteobacteria), Haemophillus (Firmicutes) and Leptotrichia (Fusobacteria). Paired taxa within family Enterobacteriaceae, together with genus Oribacterium, distinguish OCSCC samples from OPSCC and normal samples (p<0.05). Similarly, only HPV positive samples have an abundance of genus Gemellaceae and Leuconostoc (p<0.05). Longitudinal analyses of samples taken before and after surgery, revealed a reduction in the alpha diversity measure after surgery, together with an increase of this measure in patients that recurred (p<0.05). These results suggest that microbiota may be used as HNSCC diagnostic and prognostic biomonitors. PMID- 27260000 TI - Luminal STAT5 mediates H2AX promoter activity in distinct population of basal mammary epithelial cells. AB - Deregulated STAT5 activity in the mammary gland causes parity-dependent tumorigenesis. Epithelial cell cultures transfected with constitutively active STAT5 express higher levels of the histone H2AX than their non-transfected counterparts. Higher H2AX expression may be involved in tumorigenesis. Here, we aimed to link high STAT5 activity to H2AX-GFP expression by looking for distinct types of mammary cells that express these proteins. In vitro and in transgenic mice, only 0.2 and 0.02%, respectively, of the cells expressed the H2AX-GFP hybrid gene. Its expression correlated with that of the endogenous H2AX gene, suggesting that detectable H2AX-GFP expression marks high levels of H2AX transcript. Methylation of the H2AX promoter characterized non-GFP-expressing H2AX-GFP cells and was inversely correlated with promoter activity. Administration of 5-azacytidine increased H2AX promoter activity in an activated STAT5-dependent manner. In transgenic mice, H2AX-GFP expression peaked at pregnancy. The number of H2AX-GFP-expressing cells and GFP expression decreased in a Stat5a-null background and increased in mice expressing the hyperactivated STAT5. Importantly, H2AX-GFP activity was allocated to basal mammary cells lacking stem-cell properties, whereas STAT5 hyperactivity was detected in the adjacent luminal cells. Knockdown of RANKL by siRNA suggested its involvement in signaling between the two layers. These results suggest paracrine activation of H2AX via promoter demethylation in specific populations of basal mammary cells that is induced by a signal from neighboring luminal cells with hyper STAT5 activity. This pathway provides an alternative route for the luminally confined STAT5 to affect basal mammary cell activity. PMID- 27260001 TI - Regulation of HK2 expression through alterations in CpG methylation of the HK2 promoter during progression of hepatocellular carcinoma. AB - Hexokinase 2 (HK2) is a rate-determining enzyme in aerobic glycolysis, a process upregulated in tumor cells. HK2 expression is controlled by various transcription factors and epigenetic alterations and is heterogeneous in hepatocellular carcinomas (HCCs), though the cause of this heterogeneity is not known. DNA methylation in the HK2 promoter CpG island (HK2-CGI) and its surrounding regions (shore and shelf) has not previously been evaluated, but may provide clues about the regulation of HK2 expression. Here, we compared HK2 promoter methylation in HCCs and adjacent non-cancerous liver tissues using a HumanMethylation450 BeadChip array. We found that, while the HK2-CGI N-shore was hypomethylated, thereby enhancing HK2 expression, the HK2-CGI was itself hypermethylated in some HCCs. This hypermethylation suppressed HK2 expression by inhibiting interactions between HIF-1alpha and a hypoxia response element (HRE) located at -234/-230. HCCs that were HK2negative and had distinct promoter CGI methylation were denoted as having a HK2-CGI methylation phenotype (HK2-CIMP), which was associated with poor clinical outcome. These findings indicate that HK2-CGI N-shore hypomethylation and HK2-CGI hypermethylation affect HK2 expression by influencing the interaction between HIF 1alpha and HRE. HK2-CGI hypermethylation induces HK2 CIMP and could represent a prognostic biomarker for HCC. PMID- 27260003 TI - Is delayed ischemic preconditioning as effective on running performance during a 5km time trial as acute IPC? AB - : Ischemic preconditioning (IPC) may enhance exercise performance. Cardioprotective effects of IPC are known to re-occur 24h after the stimulus. Whether the delayed effect of IPC has similar effects as IPC on exercise performance is unknown. OBJECTIVES: Examine whether IPC applied 24h (24-IPC) before exercise is equally effective as IPC in improving exercise performance. DESIGN: Randomized, cross-over study METHODS: 12 healthy participants were randomly exposed to SHAM-session, IPC or 24-IPC before a self-paced 5km running trial on a treadmill. Subjects were blinded for time, speed and heart rate. Furthermore, heart rate, BORG, and the local tissue saturation index were measured during exercise, while lactate levels were determined after running. Using a regression model, we explored whether these parameters predicted the change in running time after IPC and 24-IPC. RESULTS: We found no differences in finish time after IPC (SHAM: 1400+/-105s, IPC: 1381+/-112s, 24-IPC: 1385+/-113s; p=0.30). However, we observed a significant positive relation between the change in finish time after IPC and 24-IPC (p=0.016; r=0.677). Using stepwise linear regression, a lower post-exercise blood lactate level after IPC or 24-IPC was significantly related to an improvement in finish time (R2=0.47, beta=-0.687, p=0.007). CONCLUSIONS: Although no significant effect of IPC or 24-IPC on exercise performance was found, individual finish time after IPC and 24-IPC were strongly correlated. Therefore, our data suggest that, at the individual level, the effects of 24-IPC are closely related to the effects of IPC. PMID- 27260002 TI - Zinc supplementation induces CD4+CD25+Foxp3+ antigen-specific regulatory T cells and suppresses IFN-gamma production by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. AB - PURPOSE: The essential trace element zinc plays a fundamental role in immune function and regulation since its deficiency is associated with autoimmunity, allergies, and transplant rejection. Thus, we investigated the influence of zinc supplementation on the Th1-driven alloreaction in mixed lymphocyte cultures (MLC), on generation of antigen-specific T cells, and analyzed underlying molecular mechanisms. METHODS: Cell proliferation and pro-inflammatory cytokine production were monitored by [3H]-thymidine proliferation assay and ELISA, respectively. Analysis of surface and intracellular T cell marker was performed by flow cytometry. Western blotting and mRNA analysis were used for Foxp3, KLF 10, and IRF-1 expression. RESULTS: Zinc supplementation on antigen-specific T cells in physiological doses (50 uM) provokes a significant amelioration of cell proliferation and pro-inflammatory cytokine production after reactivation compared to untreated controls. Zinc administration on MLC results in an increased induction and stabilization of CD4+CD25+Foxp3+ and CD4+CD25+CTLA-4+ T cells (p < 0.05). The effect is based on zinc-induced upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. However, in resting lymphocytes zinc increases IRF-1. CONCLUSION: In summary, zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets: Foxp3, KLF-10, and IRF-1. Thus, zinc can be seen as an auspicious tool for inducing tolerance in adverse immune reactions. PMID- 27260004 TI - The effects of dietary nitrate supplementation on the adaptations to sprint interval training in previously untrained males. AB - OBJECTIVES: Dietary nitrate can improve repeated high-intensity and supramaximal exercise performance, although the effect on adaptations to training has received limited attention. The purpose of this study was to investigate the effects of dietary nitrate on the response to 3-weeks of sprint interval training (SIT). DESIGN: Randomized control trial. METHODS: Twenty-seven untrained males (Age: 28+/-7 y, V?O2Max: 42+/-7mlkg-1min-1) completed an incremental exercise test at the beginning and end of the study. Participants were matched for V?O2Max and randomly assigned to a control group (CON; n=8), SIT+placebo group (PLA; n=10), or SIT+nitrate group (NIT; n=9). The SIT comprised 4-6 repeated 15 s all out sprints on a cycle ergometer, interspersed with 4min active recovery, 3-times per week. Approximately 2.5h prior to exercise, participants consumed gels containing ~0.1mmol (PLA) or ~8mmol nitrate (NIT). RESULTS: Following SIT, V?O2Max (PLA: 5%, p=0.057, d=0.34; NIT: 6.3%, p=0.041, d=0.34) and ventilatory threshold (VT) increased to a similar extent in both SIT groups. Maximum work rate tended to increase to a greater extent in NIT (8.7%, d=0.55) compared to PLA (4.7%, d=0.31, p=0.073). Fatigue index, calculated by the change in mean power from the first to the last sprint, tended to be reduced following SIT in NIT compared to PLA (PLA: 7.3+/-7.4%, NIT: 0.5+/-7.1%, p=0.058). CONCLUSIONS: While dietary nitrate supplementation does not augment improvements to V?O2Max and VT following SIT, it may improve WRmax and indices of repeated high-intensity exercise. PMID- 27260005 TI - Visualization of perimembranous ventricular septal defect with ruptured sinus of Valsalva aneurysm by three-dimensional transesophageal echocardiography and multidetector three-dimensional computed tomography. PMID- 27260006 TI - Type I interferonopathies in pediatric rheumatology. AB - Defective regulation of type I interferon response is associated with severe inflammatory phenotypes and autoimmunity. Type I interferonopathies are a clinically heterogenic group of Mendelian diseases with a constitutive activation of this pathway that might present as atypical, severe, early onset rheumatic diseases. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common. Recent studies have implicated abnormal responses to nucleic acid stimuli or defective regulation of downstream effector molecules in disease pathogenesis. As observed for IL1-beta and autoinflammatory diseases, knowledge of the defects responsible for type I interferonopathies will likely promote the development of targeted therapy. PMID- 27260008 TI - European trainees support the new European curriculum in Obstetrics and Gynaecology. PMID- 27260007 TI - Comorbidity of Alcohol and Gambling Problems in Emerging Adults: A Bifactor Model Conceptualization. AB - Addictive disorders, such as pathological gambling and alcohol use disorders, frequently co-occur at greater than chance levels. Substantive questions stem from this comorbidity regarding the extent to which shared variance between gambling and alcohol use reflects a psychological core of addictive tendencies, and whether this differs as a function of gender. The aims of this study were to differentiate both common and unique variance in alcohol and gambling problems in a bifactor model, examine measurement invariance of this model by gender, and identify substantive correlates of the final bifactor model. Undergraduates (N = 4475) from a large northwestern university completed an online screening questionnaire which included demographics, quantity of money lost and won when gambling, the South Oaks Gambling Screen, the AUDIT, gambling motives, drinking motives, personality, and the Brief Symptom Inventory. Results suggest that the bifactor model fit the data well in the full sample. Although the data suggest configural invariance across gender, factor loadings could not be constrained to be equal between men and women. As such, general and specific factors were examined separately by gender with a more intensive subsample of females and males (n = 264). Correlations with motivational tendencies, personality traits, and mental health symptoms indicated support for the validity of the bifactor model, as well as gender-specific patterns of association. Results suggest informative distinctions between shared and unique attributes related to problematic drinking and gambling. PMID- 27260009 TI - Incidence of rotavirus gastroenteritis by age in African, Asian and European children: Relevance for timing of rotavirus vaccination. AB - Variability in rotavirus gastroenteritis (RVGE) epidemiology can influence the optimal vaccination schedule. We evaluated regional trends in the age of RVGE episodes in low- to middle- versus high-income countries in three continents. We undertook a post-hoc analysis based on efficacy trials of a human rotavirus vaccine (HRV; RotarixTM, GSK Vaccines), in which 1348, 1641, and 5250 healthy infants received a placebo in Europe (NCT00140686), Africa (NCT00241644), and Asia (NCT00197210, NCT00329745). Incidence of any/severe RVGE by age at onset was evaluated by active surveillance over the first two years of life. Severity of RVGE episodes was assessed using the Vesikari-scale. The incidence of any RVGE in Africa was higher than in Europe during the first year of life (<=2.78% vs. <=2.03% per month), but much lower during the second one (<=0.86% versus <=2.00% per month). The incidence of severe RVGE in Africa was slightly lower than in Europe during the first year of life. Nevertheless, temporal profiles for the incidence of severe RVGE in Africa and Europe during the first (<=1.00% and <=1.23% per month) and second (<=0.53% and <=1.13% per month) years of life were similar to those of any RVGE. Any/severe RVGE incidences peaked at younger ages in Africa vs. Europe. In high-income Asian regions, severe RVGE incidence (<=0.31% per month) remained low during the study. The burden of any RVGE was higher earlier in life in children from low- to middle- compared with high-income countries. Differing rotavirus vaccine schedules are likely warranted to maximize protection in different settings. PMID- 27260010 TI - Screening rate for hepatitis B virus infection in patients undergoing chemotherapy in Japan. AB - BACKGROUND: The aim of this study was to investigate the screening rate for hepatitis B virus (HBV) infection, which is recommended by some guidelines for the prevention of HBV reactivation, in patients undergoing chemotherapy for malignancy in Japan. METHODS: The study subjects were 3302 patients who had received first-line chemotherapy for malignancy from Apr 2008 through Mar 2013 utilizing the Claims Database of the Japan Medical Data Center. The proportion of patients who had been tested for HBsAg (P-HBsAg) and the proportion of HBsAg negative patients who had undergone tests for anti-HBc and anti-HBs (P-HBc/HBsAb) before chemotherapy were investigated. RESULTS: P-HBsAg and P-HBc/HBsAb in all 3302 patients were 66.3 and 19.9 %, respectively. P-HBsAg in patients with solid tumors and those with hematological malignancies were 66.1 and 67.5 % (p = 0.61), respectively, and P-HBc/HBsAb were 12.3 and 75.8 % (p < 0.0001), respectively. P HBsAg in patients from cancer centers and non-cancer centers were 66.9 and 65.5 % (p = 0.43), respectively, and P-HBc/HBsAb were 25.1 and 12.4 % (p < 0.0001), respectively. P-HBsAg in patients encountered before and after the announcement of the Japanese guideline were 51.3 and 67.1 % (p < 0.001), respectively, and P HBc/HBsAb were 7.9 and 20.4 % (p = 0.01), respectively. CONCLUSIONS: The screening rate for HBV among cancer patients scheduled for chemotherapy remains unsatisfactory, especially in patients with solid tumors and those from non cancer centers. Although the figures are improving after the announcement of the Japanese guideline, intensive measures to improve awareness about HBV reactivation during/after chemotherapy are needed. PMID- 27260013 TI - Erratum: The miR-17-92 cluster counteracts quiescence and chemoresistance in a distinct subpopulation of pancreatic cancer stem cells. PMID- 27260011 TI - Study protocol for a randomized controlled trial to explore the effects of personalized lifestyle advices and tandem skydives on pleasure in anhedonic young adults. AB - BACKGROUND: Anhedonia is generally defined as the inability to feel pleasure in response to experiences that are usually enjoyable. Anhedonia is one of the two core symptoms of depression and is a major public health concern. Anhedonia has proven particularly difficult to counteract and predicts poor treatment response generally. It has often been hypothesized that anhedonia can be deterred by a healthy lifestyle. However, it is quite unlikely that a one-size-fits-all approach will be effective for everyone. In this study the effects of personalized lifestyle advice based on observed individual patterns of lifestyle behaviors and experienced pleasure will be examined. Further, we will explore whether a tandem skydive following the personalized lifestyle advice positively influences anhedonic young adults' abilities to carry out the recommended lifestyle changes, and whether this ultimately improves their self-reported pleasure. METHODS: Our study design is an exploratory intervention study, preceded by a cross-sectional survey as a screening instrument. For the survey, 2000 young adults (18-24 years old) will be selected from the general population. Based on survey outcomes, 72 individuals (36 males and 36 females) with persistent anhedonia (i.e., more than two months) and 60 individuals (30 males and 30 females) without anhedonia (non-anhedonic control group) will be selected for the intervention study. The non-anhedonic control group will fill out momentary assessments of pleasure and lifestyle behaviors three times a day, for one month. The anhedonic individuals will fill out momentary assessments for three consecutive months. After the first month, the anhedonic individuals will be randomly assigned to (1) no intervention, (2) lifestyle advice only, (3) lifestyle advice plus tandem skydive. The personalized lifestyle advice is based on patterns observed in the first month. DISCUSSION: The present study is the first to examine the effects of a personalized lifestyle advice and tandem skydive on pleasure in anhedonic young adults. Results of the present study may improve treatment for anhedonia, if the interventions are found to be effective. TRIAL REGISTRATION: Dutch Trial Register, NTR5498 , registered September 22, 2015 (retrospectively registered). PMID- 27260012 TI - Comments on: Arthroscopic tibiotalar and subtalar joint arthrodesis, published by X. Roussignol in Orthop Traumatol Surg Res. 2016 Feb;102(1 Suppl.):S195-203. PMID- 27260014 TI - Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity. AB - Historically, the first described effect of an angiotensin converting enzyme (ACE) inhibitor was an increased activity of bradykinin, one of the substrates of ACE. However, in the subsequent years, molecular models describing the mechanism of action of ACE inhibitors in decreasing blood pressure and cardiovascular risk have focused mostly on the renin-angiotensin system. Nonetheless, over the last 20 years, the importance of bradykinin in regulating vasodilation, natriuresis, oxidative stress, fibrinolysis, inflammation, and apoptosis has become clearer. The affinity of ACE appears to be higher for bradykinin than for angiotensin I, thereby suggesting that ACE inhibitors may be more effective inhibitors of bradykinin degradation than of angiotensin II production. Data describing the effect of ACE inhibition on bradykinin signaling support the hypothesis that the most cardioprotective benefits attributed to ACE inhibition may be due to increased bradykinin signaling rather than to decreased angiotensin II signaling, especially when high dosages of ACE inhibitors are considered. In particular, modulation of bradykinin in the endothelium appears to be a major target of ACE inhibition. These new mechanistic concepts may lead to further development of strategies enhancing the bradykinin signaling. PMID- 27260016 TI - Which items on the distress thermometer problem list are the most distressing? AB - PURPOSE: The importance of distress identification and management in oncology has been established. We examined the relationship between distress and unmet bio psychosocial needs, applying advanced statistical techniques, to identify which needs have the closest relationship to distress. METHODS: Oncology outpatients (n = 1066) undergoing QUICATOUCH screening in an Australian cancer centre completed the distress thermometer (DT) and problem list (PL). Principal component analysis (PCA), logistic regression and classification and regression tree (CART) analyses tested the relationship between DT score (at a cut-off point of 4) and PL items. RESULTS: Sixteen items were reported by <5 % of participants. PCA analysis identified four major components. Logistic regression analysis indicated three of these component scores, and four individual items (20 items in total) demonstrated a significant independent relationship with distress. The best CART model contained only two PL items: 'worry' and 'depression'. CONCLUSIONS: The DT and PL function as intended, quantifying negative emotional experience (distress) and identifying bio-psychosocial sources of distress. We offer two suggestions to minimise PL response time whilst targeting PL items most related to distress, thereby increasing clinical utility. To identify patients who might require specialised psychological services, we suggest the DT followed by a short, case finding instrument for patients over threshold on the DT. To identify other important sources of distress, we suggest using a modified PL of 14 key items, with the 15th item 'any other problem' as a simple safety net question. Shorter times for patient completion and clinician response to endorsed PL items will maximise acceptance and clinical utility. PMID- 27260017 TI - Kinesiology taping as an adjunct for the management of symptoms in the continuum of cancer care? PMID- 27260015 TI - Personal history and quality of life in chronic myeloid leukemia patients: a cross-sectional study using narrative medicine and quantitative analysis. AB - BACKGROUND: Tyrosine kinase inhibitors (TKIs) drastically changed the outcome of patients diagnosed with chronic myeloid leukemia (CML). Several reports indicated the advantage of continue long-term adherence associated with positive outcome. Therefore, it is important to better understand from the patient's standpoint the experience of living with the disease and the related treatment. OBJECTIVES: In this study, quantitative analysis and narrative medicine were combined to get insights on this issue in a population of 257 patients with CML in chronic phase treated with TKIs (43 % men, with a median age of 58 years, 27 % aged 31-50 years), followed for a median time of 5 years. Sixty-one percent of patients enrolled were treated in first line, whereas 37 % were treated in second line. RESULTS: The results showed more positive perceptions and acceptance in males compared to females, without impact of disease on relationships. Level of positive acceptance was more evident in elderly compared to younger patients, with a close connection with median time from diagnosis. Overall, female patients reported negative perceptions and an impact of disease on family daily living. The majority of patients understood the importance of continue adherence to treatment, with 27 % resulting less adherent (60 % for forgetfulness), even if well informed and supported by his/her physician. DISCUSSION AND CONCLUSIONS: Narrative medicine, in association to quantitative analysis, can help physicians to understand needs of their patients in order to improve communication. PMID- 27260019 TI - The mathematical whisker: A review of numerical models of the rat's vibrissa biomechanics. AB - The vibrissal system of the rat refers to specialized hairs the animal uses for tactile sensory perception. Rats actively move their whiskers in a characteristic way called "whisking". Interaction with the environment produces elastic deformation of the whiskers, generating mechanical signals in the whisker follicle complex. Advances in our understanding of the vibrissal complex biomechanics is of interest not only for the biological research field, but also for biomimetic approaches. The recent development of whisker numerical models has contributed to comprehending its sophisticated movements and its interactions with the follicle. The great diversity of behavioral patterns and complexities of the whisker-follicle ensemble encouraged the creation of many different biomechanical models. This review analyzes most of the whisker biomechanical models that have been developed so far. This review was written so as to render it accessible to readers coming from different research areas. PMID- 27260018 TI - The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review. AB - PURPOSE: Symptomatic adverse events (AEs) are monitored by clinicians as part of all US-based clinical trials in cancer via the U.S. National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) for the purposes of ensuring patient safety. Recently, there has been a charge toward capturing the patient perspective for those AEs amenable to patient self-reporting via patient reported outcomes (PRO). The aim of this review was to summarize the empirically reported association between analogous CTCAE and PRO ratings. METHODS: A systematic literature search was conducted using PubMed, EMBASE, Web of Science, and Cochrane databases through July 2015. From a total of 5658 articles retrieved, 28 studies met the inclusion criteria. RESULTS: Across studies, patients were of mixed cancer types, including anal, breast, cervical, chronic myeloid leukemia, endometrial, hematological, lung, ovarian, pelvic, pharyngeal, prostate, and rectal. Given this mixture, the AEs captured were variable, with many common across studies (e.g., dyspnea, fatigue, nausea, neuropathy, pain, vomiting), as well as several that were disease-specific (e.g., erectile dysfunction, hemoptysis). Overall, the quantified association between CTCAE and PRO ratings fell in the fair to moderate range and had a large variation across the majority of studies (n = 21). CONCLUSIONS: The range of measures used and symptoms captured varied greatly across the reviewed studies. Regardless of concordance metric employed, reported agreement between CTCAE and PRO ratings was moderate at best. To assist with reconciliation and interpretation of these differences toward ultimately improving patient care, an important next step is to explore approaches to integrate PROs with clinician reporting of AEs. PMID- 27260020 TI - Equine subchondral bone failure threshold under impact compression applied through articular cartilage. AB - Subchondral bone microdamage due to high-impact loading is a key factor leading to post-traumatic knee osteoarthritis. A quantified assessment of the mechanical characteristics of subchondral bone at the tissue-level is essential to study the mechanism of impact-induced microdamage. We combined mechanical impact testing of equine cartilage-bone with uCT image-based finite element models (MUFEM) of each specimen to determine subchondral bone (including calcified cartilage: CCSB) elastic tissue modulus and local stresses and strains associated with micro fractures within the CCSB tissue. The material properties of each specimen specific MUFEM were iteratively adjusted to match the FE-predicted stress-strain curves with experimental results. Isotropic homogeneous material properties for both uncalcified cartilage (UC) and CCSB were assumed. UC large-deformation was simulated using hyperelastic material properties. Final UC shear and CCSB tissue elastic modulus of G=38+/-20MPa and E(t)=3.3+/-0.7GPa were achieved after fit procedure. The results suggested that initial failure in CCSB occurred at local tensile and compressive stresses of 29.47+/-5.34 MPa and 64.3+/-21.3MPa, and tensile and compressive strains of 1.12+/-0.06% and 1.99+/-0.41%, respectively. Tissue-level material properties can be used in finite element modeling of diarthrodial joints under impact loading, and also in designing artificial cartilage-bone to replace the damaged tissue in the joint. Results can provide an estimate for the threshold of initial failure in subchondral bone tissue due to an impact compression transmitted through the overlying articular cartilage. PMID- 27260021 TI - Micro-Finite Element analysis will overestimate the compressive stiffness of fractured cancellous bone. AB - Recently, micro-Finite Element (micro-FE) analysis based on High Resolution peripheral Quantitative CT (HRpQCT) images was introduced to quantify the state of fracture healing (de Jong et al., 2014). That study suggested that the direct post-fracture stiffness may be overestimated by micro-FE. The aim of this study was to investigate this further by measuring the loss in stiffness of cancellous bone samples under compressive loading and to compare this with predictions based on micro-FE analyses and bone microstructural and fracture morphology. Sixty porcine trabecular cores were micro-CT scanned and tested in compression before and after inducing a fracture in 4 different manners. The loss in stiffness as measured in the experiment was compared to that calculated from micro-FE analysis. Additionally, bone morphology parameters and fracture thickness were calculated. The experimentally measured loss in stiffness ranged from 37% to 80%. The losses calculated from the micro-FE analyses were lower and ranged from 36% to 61%, while in one case an increase in stiffness was calculated. For 2 of the 4 experiments, the results of the experiment and micro-FE analyses were significantly different. Only for very smooth fractures good agreement was obtained between FE and experimental results. The loss in stiffness did not correlate with any investigated bone morphology parameter or the thickness of the fracture region. It was concluded that micro-FE analysis can severely overestimate the stiffness of fractured bone depending on the type of fracture, but in the case of smooth fractures good estimates are possible. PMID- 27260022 TI - The EMPA-REG outcome study: critical appraisal and potential clinical implications. AB - Diabetes health care professionals have to face a study with results of incomparable success in secondary and tertiary cardiovascular disease prevention. In the past, no studies in patients with type 2 diabetes resulted to be successful in inducing an improvement of cardiovascular prognosis, no matter whether they were focused on a target, on life-style or on pharmacological intervention. On a clinical perspective, should the diabetologist's way to think about the anti-diabetic therapy of patients on secondary cardiovascular prevention change based on the results of Empa-Reg outcome? Due to the complexity of the clinical picture of patients with type 2 diabetes, a tailored therapy based on targets, complications, co-morbidity, familial and social environment, personal and cultural features must be conceived and applied in starting pharmacological therapy; however, the question whether should we consider empagliflozin as first choice therapy in individuals with type 2 diabetes exposed to high cardiovascular risk, the Empa-Reg outcome-like patient, awaits now for an answer. Waiting for data confirming the results of the Empa-Reg outcome study, this report goes through the good reasons in support of this way of thinking, but at the same time explores the many unanswered questions raising potential concerns about this clinical choice. PMID- 27260023 TI - Fluorescence detection of intracellular cadmium with Leadmium Green. AB - Leadmium Green is a commercially available, small molecule, fluorescent probe advertised as a detector of free intracellular cadmium (Cd(2+)) and lead (Pb(2+)). Leadmium Green has been used in various paradigms, such as tracking Cd(2+) sequestration in plant cells, heavy metal export in protozoa, and Pb(2+) absorption by vascular endothelial cells. However very little information is available regarding its affinity and selectivity for Cd(2+), Pb(2+), and other metals. We evaluated the in vitro selectivity of Leadmium Green using spectrofluorimetry. Consistent with manufacturer's claims, Leadmium Green was sensitive to Cd(2+) (KD ~600 nM) and also Pb(2+) (KD ~9.0 nM) in a concentration dependent manner, and furthermore proved insensitive to Ca(2+), Co(2+), Mn(2+) and Ni(2+). Leadmium Green also responded to Zn(2+) with a KD of ~82 nM. Using fluorescence microscopy, we evaluated Leadmium Green in live mouse hippocampal HT22 cells. We demonstrated that Leadmium Green detected ionophore-mediated acute elevations of Cd(2+) or Zn(2+) in a concentration-dependent manner. However, the maximum fluorescence produced by ionophore-delivered Zn(2+) was much less than that produced by Cd(2+). When tested in a model of oxidant-induced liberation of endogenous Zn(2+), Leadmium Green responded weakly. We conclude that Leadmium Green is an effective probe for monitoring intracellular Cd(2+), particularly in models where Cd(2+) accumulates rapidly, and when concomitant fluctuations of intracellular Zn(2+) are minimal. PMID- 27260080 TI - Role of Klotho in migration and proliferation of human dermal microvascular endothelial cells. AB - PURPOSE: To examine the possible role of Klotho (Kl) in human microvasculature. METHODS: The expression level of Kl in primary human dermal microvascular endothelial cells (HDMECs) and primary human dermal fibroblasts (HFb) was detected by real-time polymerase chain reaction amplification (qRT-PCR), Western blot analyses and immunohistochemistry. Migration of HDMECs and HFb was examined in monolayer wound healing "scratch assay" and Transwell assay. Proliferation of these cells was examined using Cell Proliferation BrdU incorporation assay. RESULTS: Our results have shown that downregulation of Kl abrogated HDMECs migration after 48h. On the other hand, migration of HFb significantly increased after blocking Kl. Lack of Kl decreased expression of genes involved in the activation of endothelial cells and enhanced expression of genes involved in extracellular matrix remodeling and organization of connective tissue. CONCLUSIONS: This study for the first time provides the evidence that Kl is expressed in HDMECs and HFb. Additionally, we have demonstrated that Kl is implicated in the process of angiogenesis of human dermal microvasculature. PMID- 27260081 TI - Citizen science or scientific citizenship? Disentangling the uses of public engagement rhetoric in national research initiatives. AB - BACKGROUND: The language of "participant-driven research," "crowdsourcing" and "citizen science" is increasingly being used to encourage the public to become involved in research ventures as both subjects and scientists. Originally, these labels were invoked by volunteer research efforts propelled by amateurs outside of traditional research institutions and aimed at appealing to those looking for more "democratic," "patient-centric," or "lay" alternatives to the professional science establishment. As mainstream translational biomedical research requires increasingly larger participant pools, however, corporate, academic and governmental research programs are embracing this populist rhetoric to encourage wider public participation. DISCUSSION: We examine the ethical and social implications of this recruitment strategy. We begin by surveying examples of "citizen science" outside of biomedicine, as paradigmatic of the aspirations this democratizing rhetoric was originally meant to embody. Next, we discuss the ways these aspirations become articulated in the biomedical context, with a view to drawing out the multiple and potentially conflicting meanings of "public engagement" when citizens are also the subjects of the science. We then illustrate two uses of public engagement rhetoric to gain public support for national biomedical research efforts: its post-hoc use in the "care.data" project of the National Health Service in England, and its proactive uses in the "Precision Medicine Initiative" of the United States White House. These examples will serve as the basis for a normative analysis, discussing the potential ethical and social ramifications of this rhetoric. We pay particular attention to the implications of government strategies that cultivate the idea that members of the public have a civic duty to participate in government-sponsored research initiatives. We argue that such initiatives should draw from policy frameworks that support normative analysis of the role of citizenry. And, we conclude it is imperative to make visible and clear the full spectrum of meanings of "citizen science," the contexts in which it is used, and its demands with respect to participation, engagement, and governance. PMID- 27260083 TI - [Ischemic stroke after intracranial occlusion of the left main coronary artery : Interventional radiological treatment versus i.v. thrombolysis therapy alone]. PMID- 27260084 TI - Retrospective analysis of physical therapy utilization by the specificity of the diagnosis and order written on the referral. AB - BACKGROUND: Arguments against reimbursement for direct access to physical therapy (PT) are that a physician examination is necessary to diagnose and that there is a potential for increased cost. OBJECTIVE: To determine what percentage of PT referrals had a specific diagnosis and treatment orders. Additionally, specific and non-specific diagnoses and treatment orders were compared in regards to PT units billed, average visits per referral, and average cost per referral. METHODS: The charts of 1,000 patients treated in outpatient PT underwent a retrospective chart review. Interferential statistics were used to determine if there was a statistically significant difference between specific and non specific diagnoses and treatment orders in regard to PT units billed, average visits per referral, and average cost per referral. RESULTS: Twenty-nine percent of all referring diagnoses were non-specific in nature and 58% contained treatment orders that were non-specific. Charts with a specific diagnosis had a statistically significant higher utilization as compared to non-specific diagnoses (p <= 0.001). Patients with a specific treatment order also displayed a statistically significant larger average in billed units, average visits per referral, and average reimbursement per referral than those without a specific treatment order (p <= 0.0001). CONCLUSION: Our findings suggest that a physician diagnosis and referral may not be required to direct care for patients seeking PT services. Third-party payers that require a physician referral for PT services may be delaying access to healthcare and increasing costs. PMID- 27260085 TI - The development of a peak-time criterion for designing controlled-release devices. AB - This work consists of estimating dynamic characteristics for topically-applied drugs when the magnitude of the flux increases to a maximum value, called peak flux, before declining to zero. This situation is typical of controlled-released systems with a finite donor or vehicle volume. Laplace transforms were applied to the governing equations and resulted in an expression for the flux in terms of the physical characteristics of the system. After approximating this function by a second-order model, three parameters of this reduced structure captured the essential features of the original process. Closed-form relationships were then developed for the peak flux and time-to-peak based on the empirical representation. Three case studies that involve mechanisms, such as diffusion, partitioning, dissolution and elimination, were selected to illustrate the procedure. The technique performed successfully as shown by the ability of the second-order flux to match the prediction of the original transport equations. A main advantage of the proposed method is that it does not require a solution of the original partial differential equations. Less accurate results were noted for longer lag times. PMID- 27260082 TI - American Brachytherapy Task Group Report: Adjuvant vaginal brachytherapy for early-stage endometrial cancer: A comprehensive review. AB - This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the postoperative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early-stage endometrial cancer patients results in very low rates of vaginal recurrence (0-3.1%) with low rates of late toxicity which are primarily vaginal in nature. Post-Operative Radiation Therapy in Endometrial Cancer 2 (PORTEC-2) supports that VBT results in noninferior rates of vaginal recurrence compared to external beam radiotherapy for the treatment of high-intermediate risk patients. VBT as a boost after external beam radiotherapy, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians prefer joint decision making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multidisciplinary setting, and patients should be counseled properly regarding the risks and benefits of adjuvant therapy. PMID- 27260086 TI - Development of hematin conjugated PLGA nanoparticle for selective cancer targeting. AB - Targeted nanomedicine for cancer therapy has gained widespread popularity and is being extensively explored. Porphyrins have intrinsic tumor localizing ability and have been studied for photodynamic therapy. However, they have not been used as cancer targeting agents for nanomedicines. In this study, PLGA nanoparticles were formulated and an iron-containing blood porphyrin, hematin was conjugated to the surface of the nanoparticles to investigate selectivity towards cancer cell and cellular internalization. Hematin was previously shown to facilitate growth and proliferation of cancer cells. PLGA nanoparticles were characterized by FE SEM, AFM, DLS, and Zeta potential analyzer. The conjugation of hematin was confirmed by FTIR. HeLa cells were used to study tumor selectivity and uptake. Hematin conjugated particles (zeta potential: -15.19mV) showed higher affinity towards the cancer cells than the control particles. The result indicated that the particles were internalized by heme carrier protein-1. Together these data suggest that hematin is a promising cancer targeting material for nanotherapeutics. PMID- 27260087 TI - The effects of chitosan/miR-200c nanoplexes on different stages of cancers in breast cancer cell lines. PMID- 27260088 TI - Effect of solubility enhancement on nasal absorption of meloxicam. AB - Besides the opioids the standard management of the World Health Organization suggests NSAIDs (non-steroidal anti-inflammatory drugs) alone or in combination to enhance analgesia in malignant and non-malignant pain therapy. The applicability of NSAIDs in a nasal formulation is a new approach in pharmaceutical technology. In order to enhance the nasal absorption of meloxicam (MX) as an NSAID, its salt form, meloxicam potassium monohydrate (MXP), registered by Egis Plc., was investigated in comparison with MX. The physico chemical properties of the drugs (structural analysis, solubility and dissolution rate) and the mucoadhesivity of nasal formulations were controlled. In vitro and in vivo studies were carried out to determine the nasal applicability of MXP as a drug candidate in pain therapy. It can be concluded that MX and MXP demonstrated the same equilibrium solubility at the pH5.60 of the nasal mucosa (0.017mg/ml); nonetheless, MXP indicated faster dissolution and a higher permeability through the synthetic membrane. The animal studies justified the short Tmax value (15min) and the high AUC of MXP, which is important in acute pain therapy. It can be assumed that the low mucoadhesivity of MXP spray did not increase the residence time in the nasal cavity, and the elimination from the nasal mucosa was therefore faster than in the case of MX. Further experiments are necessary to prove the therapeutic relevance of this MXP-containing innovative intranasal formulation. PMID- 27260089 TI - Supersaturation of zafirlukast in fasted and fed state intestinal media with and without precipitation inhibitors. AB - Poor water solubility is a bottle neck in the development of many new drug candidates, and understanding and circumventing this is essential for a more effective drug development. Zafirlukast (ZA) is a leukotriene antagonist marketed for the treatment of asthma (Accolate(r)). ZA is poorly water soluble, and is formulated in an amorphous form (aZA) to improve its solubility and oral bioavailability. It has been shown that upon dissolution of aZa, the concentration of ZA in solution is supersaturated with respect to its stable crystalline form (ZA monohydrate), and thus, in theory, the bioavailability increases upon amorphization of ZA. The polymers hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidone (PVP), often used as stabilizers of the supersaturated state, are in the excipient list of Accolate(r). It is not recommended to take Accolate(r) with food, as this reduces the bioavailability by 40%. The aim of this study was to investigate the effect of simulated fasted and fed state intestinal media as well as the effect of HPMC and PVP on the supersaturation and precipitation of ZA in vitro. Supersaturation of aZA was studied in vitro in a small scale setup using the MUDiss ProfilerTM. Several media were used for this study: One medium simulating the fasted state intestinal fluids and three media simulating different fed state intestinal fluids. Solid state changes of the drug were investigated by small angle x-ray scattering. The duration wherein aZA was maintained at a supersaturated state was prolonged in the presence of HPMC and lasted more than 20h in the presence of PVP in a fasted state intestinal medium. The presence of PVP increased the concentration of drug dissolved in the supersaturated state. The duration of supersaturation was shorter in fed than in a fasted state simulated intestinal media, but the concentration during supersaturation was higher. It was thus not possible to predict any positive or negative food effects from the dissolution/precipitation curves from different media. Lipolysis products in the fed state simulated media seemed to cause both a negative effect on the duration of supersaturation, and an increased drug concentration during supersaturation. In contrast, when testing the effect of a fed state simulated medium compared to the fasted state medium, in the presence of PVP, a clear negative effect was seen on the dissolution/precipitation curved of the fed state medium. The drug concentration during supersaturation was marginally different in the two media, but a precipitation of ZA was seen in the fed state medium, which was not observed in the fasted state medium. Solid state transformation from aZA to ZA monohydrate (mhZA) upon precipitation of the supersaturated solutions was confirmed by small angle x-ray scattering. All of these results can explain the described in vivo behavior of ZA. For ZA simple dissolution experiments in vitro can be used to examine supersaturation, effectiveness of PI and potential food effects on these. PMID- 27260090 TI - Vesicles Cytoplasmic Injection: An Efficient Technique to Produce Porcine Transgene-Expressing Embryos. AB - The use of vesicles co-incubated with plasmids showed to improve the efficiency of cytoplasmic injection of transgenes in cattle. Here, this technique was tested as a simplified alternative for transgenes delivery in porcine zygotes. To this aim, cytoplasmic injection of the plasmid alone was compared to the injection with plasmids co-incubated with vesicles both in diploid parthenogenic and IVF zygotes. The plasmid pcx-egfp was injected circular (CP) at 3, 30 and 300 ng/MUl and linear (LP) at 30 ng/MUl. The experimental groups using parthenogenetic zygotes were as follows: CP naked at 3 ng/MUl (N = 105), 30 ng/MUl (N = 95) and 300 ng/MUl (N = 65); Sham (N = 105); control not injected (N = 223); LP naked at 30 ng/MUl (N = 78); LP vesicles (N = 115) and Sham vesicles (N = 59). For IVF zygotes: LP naked (N = 44) LP vesicles (N = 94), Sham (N = 59) and control (N = 79). Cleavage, blastocyst and GFP+ rates were analysed by Fisher's test (p < 0.05). The parthenogenic CP naked group showed lower cleavage respect to control (p < 0.05). The highest concentration of plasmids to allow development to blastocyst stage was 30 ng/MUl. There were no differences in DNA fragmentation between groups. The parthenogenic LP naked group resulted in high GFP rates (46%) and also allowed the production of GFP blastocysts (33%). The cytoplasmic injection with LP vesicles into parthenogenic zygotes allowed 100% GFP blastocysts. Injected IVF showed higher cleavage rates than control (p < 0.05). In IVF zygotes, only the use of vesicles produced GFP blastocysts. The use of vesicles co-incubated with plasmids improves the transgene expression efficiency for cytoplasmic injection in porcine zygotes and constitutes a simple technique for easy delivery of plasmids. PMID- 27260091 TI - Native recombinant kisspeptin can induce gnrh1 and kissr2 expression in Paralichthys olivaceus in vitro. AB - Kisspeptins have been described as one of the most potent activators of the hypothalamic-pituitary-gonadal axis. Kisspeptins control the onset of reproductive functions during puberty by directly stimulating the neuronal activity and release of gonadotropin-releasing hormone (GnRH). The function of kisspeptins has been investigated in vivo and in vitro. In our study, three kinds of recombinant kisspeptin proteins were expressed in Escherichia coli. Kisspeptin fragments Kp54, Kp44, and Kp10 translated from Paralichthys olivaceus kiss2 gene were then obtained. Kp44 contained 44 amide acids (aa) which are the same as the N-terminal of Kp54; Kp10 shares the same 10 aa with the C-terminal of Kp54 but Kp10 also contains some other amide acids. In the dose course of treatments with prokaryotically expressed peptides, Kp54 and Kp10 could induce the expression of kissr2 and gnrh1; by contrast, Kp44 could not induce a similar expression. These results provided direct evidence that the core decapeptide of kisspeptin is necessary to ensure its biological functions. In the time course of the Kp54 treatments on two kinds of cultured brain cells, different patterns of kissr2 and gnrh1 mRNA suggested that the responses of these cells to kisspeptins depends on cell type and treatment duration. Thus, our research provided alternative methods to investigate the functions of kisspeptin in vitro and to detect biological activities; this research also established basis for kisspeptin applications in production processes. PMID- 27260105 TI - Erratum. PMID- 27260104 TI - NF-kappaB decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model. AB - Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-kappaB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-kappaB oligo-deoxynucleotide (ODN) on wear particle induced bone loss in a murine continuous femoral particle infusion model. Ultra high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4weeks. Particle-induced bone loss was evaluated by MUCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-kappaB decoy ODN reversed or further increased the bone mineral density in the femur (3-6mm from the distal end) exposed to particles alone or particles plus LPS. NF-kappaB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-kappaB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis. STATEMENT OF SIGNIFICANCE: Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-kappaB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone-resorbing cells), and osteoblasts (bone-forming cells) could potentially mitigate this disease. Here we demonstrated that local delivery of decoy NF-kappaB oligo deoxynucleotide (ODN) mitigated ultra-high molecular weight polyethylene (UHMWPE) wear particle induced bone loss in a clinically relevant murine model. The protective effects of decoy ODN was associated with reduced macrophage infiltration and osteoclast activation, but had no significant effects on osteoblast numbers. Our study suggests that targeting NF-kappaB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced bone loss. PMID- 27260106 TI - Pattern of skin cancer among Saudi patients attending a tertiary care center in Dhahran, Eastern Province of Saudi Arabia. A 20-year retrospective study. AB - Skin cancer is the ninth most common malignancy in Saudi Arabia. It represented 3.2% of all newly diagnosed cancer cases in the year 2010. The aim of this study was to determine the epidemiology of skin cancer in relation to age, sex, and anatomic location among Saudi patients attending the Johns Hopkins Aramco Healthcare center in Dhahran, Eastern province of Saudi Arabia. We retrospectively reviewed the surgical pathology records of Saudi nationals from 1995 to 2014 at the Johns Hopkins Aramco Healthcare center, which directly provides for the healthcare needs of Saudi Aramco company employees and dependents in the Eastern Province of Saudi Arabia. Tumor metastases to skin, skin involvement by primary breast carcinoma, and B-cell leukemia/lymphoma with secondary involvement by skin were excluded. The total number of primary skin tumors was 204. The commonest cutaneous malignancies were basal cell carcinoma (36%) followed by squamous cell carcinoma (23%), with the head and neck being the commonest location for both tumors. Mycosis fungoides (MF) was the third most common malignancy (11%). Malignant melanoma was the fourth commonest skin malignancy (7%) with the lower extremities being the commonest location. The four most common skin cancers in our tertiary center in the Eastern Province of Saudi Arabia were squamous cell carcinoma, basal cell carcinoma, MF, and malignant melanoma. Other regions of Saudi Arabia report a similar pattern of skin cancers as our center, with MF having a higher frequency at our center. PMID- 27260107 TI - Transfusion-Transmitted Babesia microti. AB - Because testing of donors for Babesia microti has become available, it is important to determine the kinds of patients who should receive B microti-tested blood. We searched PubMed, AABB abstracts, and FDA Web site to identify all cases of transfusion-transmitted babesiosis (TTB). Cases were analyzed for underlying medical condition, age, presence of spleen, and reason for transfusion in relation to 5 classes of recipient outcome severity. Sixty-seven reports included 256 transfusion cases where donor tested positive for B microti, 165 of which resulted in TTB. Sixty recipients did not develop disease or become test positive, and test results were not known for 31 more. The 165 cases of TTB involved hematologic (19%), neonate (10%), cardiovascular (8%), and gastrointestinal (6%) patients. Thirty-two (19%) of the 165 infected patients died with death attributed to babesiosis in 25 of the cases. Nine (5%) were asymptomatic, 27 (16%) were symptomatic but had uncomplicated disease, and 16 (10%) had complicated disease. The severity of disease was mixed among many disease categories. Patients >65 years of age included the largest number of recipients (59/165, 36%) and deaths (11/32, 34%), although deaths occurred in other age groups as well. TTB cases were predominantly due to red cells (133 of 140 specified units), with red blood cell units processed in a variety of ways and at all storage duration. TTB with complicated babesiosis and/or death occurred in patients of all age groups and with a variety of underlying medical conditions. PMID- 27260108 TI - Autologous Blood Transfusion in Sports: Emerging Biomarkers. AB - Despite being prohibited by the World Anti-Doping Agency, blood doping through erythropoietin injection or blood transfusion is frequently used by athletes to increase oxygen delivery to muscles and enhance performance. In contrast with allogeneic blood transfusion and erythropoietic stimulants, there is presently no direct method of detection for autologous blood transfusion (ABT) doping. Blood reinfusion is currently monitored with individual follow-up of hematological variables via the athlete biological passport, which requires further improvement. Microdosage is undetectable, and suspicious profiles in athletes are often attributed to exposure to altitude, heat stress, or illness. Additional indirect biomarkers may increase the sensitivity and specificity of the longitudinal approach. The emergence of "-omics" strategies provides new opportunities to discover biomarkers for the indirect detection of ABT. With the development of direct quantitative methods, transcriptomics based on microRNA or messenger RNA expression is a promising approach. Because blood donation and blood reinfusion alter iron metabolism, quantification of proteins involved in metal metabolism, such as hepcidin, may be applied in an "ironomics" strategy to improve the detection of ABT. As red blood cell (RBC) storage triggers changes in membrane proteins, proteomic methods have the potential to identify the presence of stored RBCs in blood. Alternatively, urine matrix can be used for the quantification of the plasticizer di(2-ethyhexyl)phthalate and its metabolites that originate from blood storage bags, suggesting recent blood transfusion, and have an important degree of sensitivity and specificity. This review proposes that various indirect biomarkers should be applied in combination with mathematical approaches for longitudinal monitoring aimed at improving ABT detection. PMID- 27260109 TI - The association of physical activity, cognitive processes and automobile driving ability in older adults: A review of the literature. AB - As the number of older adults in the United States grows, the number of automobile drivers over the age of 65 will also increase. Several cognitive processes necessary for automobile driving are vulnerable to age-related decline. These include declines in executive function, working memory, attention, and speed of information processing. The benefits of physical activity on physical, psychological and particular cognitive processes are well-documented; however few studies have explored the relationship between physical activity and driving ability in older adults or examined if cognitive processes mediate (or moderate) the effect of physical activity on driving ability. The purpose of this paper is to review the existing literature regarding physical activity, cognition and automobile driving. Recommendations for further research and utility of the findings to nursing and the health care team are provided. PMID- 27260110 TI - Which characteristics of nursing home residents relate to factors influencing their dignity? AB - Aim of this study was to explore which characteristics of nursing home residents relate to factors influencing their dignity. Questionnaires containing the Measurement Instrument for Dignity AMsterdam - for Long-Term Care facilities (MIDAM-LTC) were administered to 95 nursing home residents, residing on the general medical wards of six nursing homes in the Netherlands. Associations between residents' characteristics and each MIDAM-LTC item as well as the total number of items considerably influencing dignity were calculated. Results showed that not being optimistic, being male and/or being heavily dependent predispose nursing home residents to have their dignity undermined. Residents with these characteristics should therefore be given special attention in the provision of dignity-conserving care. Age, cultural background, religion, length of stay and socioeconomic status were very rarely related to individual MIDAM-LTC items. Knowledge of associations between characteristics and factors undermining dignity can be used to raise nursing home staff's sensitivity toward these factors. PMID- 27260111 TI - Correction. PMID- 27260112 TI - Thank You ASE. PMID- 27260113 TI - Training Tomorrow's Cardiovascular Sonographers. PMID- 27260114 TI - Your Steering Committee Hard at Work. PMID- 27260115 TI - Development of different diagnostic techniques for Endolimax piscium (archamoebae) and their applicability in Solea senegalensis clinical samples. AB - Systemic amoebiasis of sole is caused by Endolimax piscium, a cryptic parasitic archamoeba whose epidemiology and pathogeny are yet unknown. To establish reliable detection methods for this parasite, a battery of molecular diagnostic tools (ISH, PCR and qPCR) were developed and evaluated with a panel of clinical samples from symptomatic diseased fish and from apparently normal animals of different stocks. As there is neither enough background information on the epidemiology of the disease nor a validated reference method, comparison of tests used a composite reference method approach. The ISH technique was the most specific and sensitive in intestine samples and particularly useful as a reference confirmatory method, while the best method in muscle samples was qPCR. Application of the tests to asymptomatic fish demonstrated presence of parasites in a large proportion (>25%) of their intestines, suggesting that this is the point of entry of the amoebae and the initial stage in the development of the disease. The triggering factors that facilitate the breaching of the intestinal barrier by E. piscium, causing granulomatous lesions in other organs and systemic spreading, are not completely understood but our results point to the connective tissue as a preferential target for parasite development and migration. PMID- 27260116 TI - False overt hyperthyroidism by interference in immunoassay. PMID- 27260117 TI - Dexmedetomidine Infusion may Cause Agitation During Procedural Sedation. PMID- 27260118 TI - Notalgia Paresthetica, A Clinical Series and Review. PMID- 27260119 TI - Regarding Ultrasound-Guided Pararadicular Injections in the Lumbar Spine by Kim et al. PMID- 27260120 TI - Prescription Drug Monitoring Programs Needed to Manage Opioid Use in Asia Pacific. PMID- 27260121 TI - Nonylphenol effects on human prostate non tumorigenic cells. AB - Nonylphenol (NP) is an industrial chemical with estrogenic activity both in vivo and in vitro; estrogens play a critical role in the development of prostate and may be the cause of some pathological states, including cancer. In this study we examined the effects of NP on human prostate non tumorigenic epithelial cells (PNT1A) investigating on cell proliferation, interaction with estrogen receptors (ERs) and gene expression of genes involved in prostate diseases. We found that NP affects cell proliferation at 10(-6)M, promoting a cytoplasm-nucleus translocation of ERalpha and not ERbeta, like the natural estrogen 17beta estradiol (E2). Moreover, we showed that NP enhances gene expression of key regulators of cell cycle. Estrogen selective antagonist ICI182780 in part reverted the observed effects of NP. These results confirm the estrogenic activity of NP and suggest that other transduction pathways may be involved in NP action on prostate. PMID- 27260122 TI - Correlates of self-report chronic insomnia disorders with 1-6 month and 6-month durations in home-dwelling urban older adults - the Shih-Pai Sleep Study in Taiwan: a cross-sectional community study. AB - BACKGROUND: To examine the correlates of insomnia disorder with different durations in home-dwelling older adults. METHODS: A cross-sectional survey in the Shih-Pai area of Taipei City, Taiwan (The Shih-Pai Sleep Study). A total 4047 subjects over the age of 65 years completed the study (2259 men and 1788 women). The Pittsburgh Sleep Quality Index and the duration of insomnia symptoms were used to identify DSM-IV 1-6 month and 6-month insomnia disorders. RESULTS: The prevalence of DSM-IV defined insomnia disorder was 5.8 %; two-thirds of these case lasted for >=6 months. The shared correlates for both 1-6 and 6-month insomnia disorders were gender (women), depression and moderate pain. Pulmonary diseases were exclusively associated with 1-6 month insomnia disorder (OR: 2.57, 95 % CI: 1.46-4.52). In contrast, heart disease (OR: 1.73, 95 % CI: 1.21-2.49) and severe pain (OR: 2.34, 95 % CI: 1.14-4.40) were associated with 6-month insomnia disorder. CONCLUSION: The prevalence of persistent insomnia disorder is higher than short-term insomnia disorder. Correlates for less persistent and more persistent insomnia disorder appears to be partially different. Duration quantifiers may be important in the identification of the etiology of insomnia and further studies with follow-ups are needed to examine the order of developing insomnia disorder and associated conditions. PMID- 27260123 TI - Development and Testing of a Smartphone-Based Cognitive/Neuropsychological Evaluation System for Substance Abusers. AB - INTRODUCTION: In methamphetamine (MA) users, drug-induced neurocognitive deficits may help to determine treatment, monitor adherence, and predict relapse. To measure these relationships, we developed an iPhone app (Neurophone) to compare lab and field performance of N-Back, Stop Signal, and Stroop tasks that are sensitive to MA-induced deficits. METHODS: Twenty healthy controls and 16 MA dependent participants performed the tasks in-lab using a validated computerized platform and the Neurophone before taking the latter home and performing the tasks twice daily for two weeks. RESULTS: N-Back task: there were no clear differences in performance between computer-based vs. phone-based in-lab tests and phone-based in-lab vs. phone-based in-field tests. Stop-Signal task: difference in parameters prevented comparison of computer-based and phone-based versions. There was significant difference in phone performance between field and lab. Stroop task: response time measured by the speech recognition engine lacked precision to yield quantifiable results. There was no learning effect over time. On an average, each participant completed 84.3% of the in-field NBack tasks and 90.4% of the in-field Stop Signal tasks (MA-dependent participants: 74.8% and 84.3%; healthy controls: 91.4% and 95.0%, respectively). Participants rated Neurophone easy to use. CONCLUSION: Cognitive tasks performed in-field using Neurophone have the potential to yield results comparable to those obtained in a laboratory setting. Tasks need to be modified for use as the app's voice recognition system is not yet adequate for timed tests. PMID- 27260124 TI - Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study. AB - BACKGROUND: Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees. METHODS: A total of 421 male subjects (mean age +/- SD, 54.1 +/- 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on elevated levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum gamma-glutamyl transpeptidase (GGT) was then conducted. RESULTS: For men with Mt5178C, after adjustment for age, body mass index, alcohol consumption, habitual smoking, green tea consumption, antihypertensive treatment, and antidiabetic treatment, elevated levels of serum AST, as defined as >=30 U/L; those of serum ALT, as defined as >=25 U/L; or those of serum GGT, as defined as >=60 or >51 U/L, may depend on coffee consumption (P for trend = 0.013, P for trend <0.001, P for trend = 0.002, and P for trend <0.001, respectively). On the other hand, no significant joint effects of Mt5178A genotype and coffee consumption on elevated levels of serum liver enzymes were observed. CONCLUSIONS: The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees. PMID- 27260125 TI - Pharmacological characterization of emerging synthetic cannabinoids in HEK293T cells and hippocampal neurons. AB - There has been a worldwide proliferation of synthetic cannabinoids that have become marketed as legal alternatives to cannabis (marijuana). Unfortunately, there is a dearth of information about the pharmacological effects of many of these emerging synthetic cannabinoids (ESCs), which presents a challenge for regulatory authorities that need to take such scientific evidence into consideration in order to regulate ECSs as controlled substances. We aimed to characterize the pharmacological properties of ten ESCs using two cell based assays that enabled the determination of potency and efficacy relative to a panel of well-characterized cannabinoids. Agonist-mediated inhibition of forskolin stimulated cyclic adenosine monophosphate (cAMP) levels was monitored in live HEK293T cells transfected with human cannabinoid receptor 1 gene (CNR1) and pGloSensor-22F. Pharmacological analysis of this data indicated that all of the ESCs tested were full agonists, with the following rank order of potency: Win 55212-2~5F-PB-22~AB-PINACA~EAM-2201~MAM-2201>JWH-250~ PB-22>AKB48 N-(5FP)>AKB 48~STS-135>XLR-11. Assessment of agonist-stimulated depression of Ca(2+) transients was also used to confirm the efficacy of five ESCs (XLR-11, JWH-250, AB-PINACA, 5F-PB-22, and MAM-2201) in cultured primary hippocampal neurons. This work aims to help inform decisions made by regulatory agencies concerned with the profusion of these poorly characterized recreational drugs. PMID- 27260126 TI - Cigarette smoke extract alters the cell cycle via the phospholipid transfer protein/transforming growth factor-beta1/CyclinD1/CDK4 pathway. AB - This study was aimed to investigate the effect of phospholipid transfer protein (PLTP) on cigarette smoke extract (CSE)-induced alteration of the cell cycle and the possible mechanism. Male Wistar rats and the rat alveolar epithelial cell line (RLE-6TN) were exposed to normal air or different concentrations of CSE. Then PLTP siRNA was transfected into cells and an inhibitor of transforming growth factor-beta1 (TGF-beta1) was administered prior to CSE exposure. Histological changes and cell cycle stage were recorded, as were the expression levels of PLTP, TGF-beta1, CyclinD1 and CDK4. Resulting morphological changes included diffuse interstitial substance incrassation and elevated alveolar rupturing. Flow cytometry analysis revealed an increase in the number of cells in the G1 phase in a time- and dose-related manner. Both PLTP and TGF-beta1 were up regulated at protein and mRNA levels, whereas CyclinD1 and CDK4 expression was down-regulated after CSE exposure. Furthermore, PLTP siRNA significantly suppressed CSE-induced TGF-beta1 expression, resulting in up-regulation of CyclinD1 and CDK4, but the TGF-beta1 inhibitor was not able to abrogate CSE induced PLTP over-expression. In conclusion, PLTP may operate upstream of the TGF beta1/CyclinD1/CDK4 pathway and may mediate the CSE-induced G1 arrest in RLE-6TN cells. Our work provides some new insight into the relation between PLTP and cell cycle progression. PMID- 27260128 TI - Contemporary management of benign parotid tumours - the increasing evidence for extracapsular dissection. AB - Benign parotid tumours have historically often been managed surgically by superficial parotidectomy. While this approach usually gives a generous cuff of surrounding normal parotid tissue to increase tumour margins, it requires a much larger incision than the increasingly used extracapsular dissection (ECD) technique. Furthermore, superficial parotidectomy can result in marked facial hollowing, Frey syndrome and an increased risk of both temporary and permanent facial nerve weakness. ECD has been popularised as a safe alternative to parotidectomy primarily for the removal of mobile, benign parotid tumours with safe outcomes and reduced risk to the facial nerve. In this article, we review the growing body of evidence for ECD and include our own experience confirming the move away from superficial parotidectomy in contemporary practice for the treatment of benign parotid tumours. PMID- 27260127 TI - Immunoadolescence: Neuroimmune development and adolescent behavior. AB - The brain is increasingly appreciated to be a constantly rewired organ that yields age-specific behaviors and responses to the environment. Adolescence in particular is a unique period characterized by continued brain maturation, superimposed with transient needs of the organism to traverse a leap from parental dependence to independence. Here we describe how these needs require immune maturation, as well as brain maturation. Our immune system, which protects us from pathogens and regulates inflammation, is in constant communication with our nervous system. Together, neuro-immune signaling regulates our behavioral responses to the environment, making this interaction a likely substrate for adolescent development. We review here the identified as well as understudied components of neuro-immune interactions during adolescence. Synaptic pruning, neurite outgrowth, and neurotransmitter release during adolescence all regulate and are regulated by-immune signals, which occur via blood-brain barrier dynamics and glial activity. We discuss these processes, as well as how immune signaling during this transitional period of development confers differential effects on behavior and vulnerability to mental illness. PMID- 27260130 TI - Advanced topical formulations (ATF). AB - Topical formulations aim to target the skin for a variety of cosmetic, protective or therapeutic needs. Despite the use of creams and ointments over the millennia, the bioavailability of actives from topical preparations remains quite low, often not exceeding 1-2% of the applied dose. In this review we examine the reasons underlying the poor performance of topical preparations. We also outline a rational approach, based on Fick's laws of diffusion, to develop advanced topical formulations. Methodologies which are currently used in research and development are critically examined and the importance of understanding the fate of the vehicle as well as the active is emphasised. Advanced topical formulation development will also be facilitated by emerging and sophisticated analytical techniques that are able to probe real time delivery of actives to the skin. A good understanding of the underlying physical chemistry of both the formulation and the skin is crucial in the development of optimised topical products. PMID- 27260129 TI - A Randomized, Open-Label, Comparative Study of Efficacy and Safety of Tolterodine Combined with Tamsulosin or Doxazosin in Patients with Benign Prostatic Hyperplasia. AB - BACKGROUND Benign prostatic hyperplasia (BPH), a common disease in men over age 50 years, often causes bladder outlet obstruction and lower urinary tract symptoms (LUTS). Alpha blockers in combination with muscarinic receptor antagonists may have the potential to improve symptoms. This study aimed to assess the efficacy and safety of doxazosin or tamsulosin combined with tolterodine extend release (ER) in patients with BPH and LUTS. MATERIAL AND METHODS In a prospective, randomized, open-label study (ChiCTR-IPR-15005763), 220 consecutive men with BPH and LUTS were allocated to receive doxazosin 4 mg and tolterodine ER 4 mg per day (doxazosin group) or tamsulosin 0.2 mg and tolterodine ER 4 mg per day (tamsulosin group). Treatment lasted 12 weeks. The primary endpoint was the international prostatic symptom score (IPSS). Secondary endpoints were quality of life (QoL) and maximum flow rate (Qmax), which were evaluated at 0, 6, and 12 weeks, and urodynamic parameters assessed at 0 and 12 weeks. RESULTS A total of 192 patients completed the trial. Baseline measurements showed no differences between the groups. After 6 weeks, IPSS improved in both groups and QoL was significantly better in the doxazosin group (P=0.01). After 12 weeks, Qmax, IPSS, QoL, intravesical pressure (Pves), and bladder compliance (BC) in the doxazosin group were significantly better than in the tamsulosin group (P=0.03, P<0.001, P<0.001, P=0.027, and P=0.044, respectively). CONCLUSIONS Administration of alpha blockers combined with muscarinic receptor blocker for 12 weeks improved LUTS in men with BPH. PMID- 27260131 TI - Real-time monitoring of the mechanism of ibuprofen-cationic dextran crystanule formation using crystallization process informatics system (CryPRINS). AB - One step aqueous melt-crystallization and in situ granulation was utilized to produce ibuprofen-cationic dextran [diethylaminoethyl dextran (Ddex)] conjugate crystanules without the use of surfactants or organic solvents. This study investigates the mechanism of in situ granulation-induced crystanule formation using ibuprofen (Ibu) and Ddex. Laboratory scale batch aqueous crystallization system containing in situ monitoring probes for particle vision measurement (PVM), UV-vis measurement and focused beam reflectance measurements (FBRM) was adapted using pre-defined formulation and process parameters. Pure ibuprofen showed nucleation domain between 25 and 64 degrees C, producing minicrystals with onset of melting at 76 degrees C and enthalpy of fusion (DeltaH) of 26.22kJ/mol. On the other hand Ibu-Ddex crystanules showed heterogeneous nucleation which produced spherical core-shell structure. PVM images suggest that internalization of ibuprofen in Ddex corona occurred during the melting phase (before nucleation) which inhibited crystal growth inside the Ddex corona. The remarkable decrease in DeltaH of the crystanules from 26.22 to 11.96kJ/mol and the presence of broad overlapping DSC thermogram suggests formation of ibuprofen-Ddex complex and crystalline-amorphous transformation. However Raman and FTIR spectra did not show any significant chemical interaction between ibuprofen and Ddex. A significant increase in dissolution efficiency from 45 to 81% within 24h and reduced burst release provide evidence for potential application of crystanules in controlled drug delivery systems. It was evident that in situ granulation of ibuprofen inhibited the aqueous crystallization process. It was concluded that in situ granulation-aqueous crystallization technique is a novel unit operation with potential application in continuous pharmaceutical processing. PMID- 27260132 TI - Synthesis and characterization of a PAMAM-OH derivative containing an acid-labile beta-thiopropionate bond for gene delivery. AB - The present report describes the synthesis of a hydroxyl terminal PAMAM dendrimer (PAMAM-OH) derivative (PAMSPF). The hydroxyls of PAMAM-OH were attached to S Methyl-l-cysteine (SMLC) via an acid-labile ester bond, named as beta thiopropionate bond, followed by modification with folic acid (FA) through a polyethylene glycol (PEG) linker. The degrees of attachment of SMLC and FA to the PAMAM-OH backbone were 83.9% and 12.8%, respectively. PAMSPF could condense DNA to form spherical nanoparticles with particle sizes of ~200nm and remain stable in the presence of heparin and nuclease. The beta-thiopropionate bond in PAMSPF was hydrolyzed completely and the DNA release rate was 95.8+/-3.3% after incubation under mildly acidic conditions at 37 degrees C for 3h. PAMSPF/DNA was less cytotoxic to KB and HepG2 cells and exhibited a higher gene transfection efficiency than native PAMAM/DNA. The uptake assays showed that PAMSPF/DNA entered KB cells within 0.5h through folate receptor-mediated endocytosis and escaped from endosomes within 2h. In addition, PAMSPF/DNA displayed long circulation time along with excellent targeting of tumor sites in vivo. These findings demonstrate that PAMSPF is an excellent carrier for safe and effective gene delivery. PMID- 27260133 TI - Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels. AB - Enhancing skin permeation is important for development of new transdermal drug delivery formulations. This is particularly relevant for non-steroidal anti inflammatory drugs (NSAIDs). To address this, semisolid gel and solid hydrogel film formulations containing gellan gum as a gelling agent were developed and the effects of penetration enhancers (dimethyl sulfoxide, isopropyl alcohol and propylene glycol) on transport of the NSAID diclofenac sodium was quantified. A transwell diffusion system was used to accelerate formulation development. After 4h, diclofenac flux from a superior formulation of the semisolid gel or the solid hydrogel film was 130+/-11MUg/cm(2)h and 108+/-7MUg/cm(2)h, respectively, and significantly greater than that measured for a currently available diclofenac sodium topical gel (30+/-4MUg/cm(2)h, p<0.05) or solution formulation (44+/ 6MUg/cm(2)h, p<0.05) under identical conditions. Over 24h diclofenac transport from the solid hydrogel film was greater than that measured for any new or commercial diclofenac formulation. Entrapment of temperature-responsive nanogels within the solid hydrogel film provides temperature-activated prolonged release of diclofenac. Diclofenac transport was minimal at 22 degrees C, when diclofenac is entrapped within temperature-responsive nanogels incorporated into the solid hydrogel film, but increased 6-fold when the temperature was increased to skin surface temperature of 32 degrees C. These results demonstrate the feasibility of the semisolid gel and solid hydrogel film formulations that can include thermo responsive nanogels for development of transdermal drug formulations with adjustable drug transport kinetics. PMID- 27260134 TI - Emerging technology: A key enabler for modernizing pharmaceutical manufacturing and advancing product quality. AB - Issues in product quality have produced recalls and caused drug shortages in United States (U.S.) in the past few years. These quality issues were often due to outdated manufacturing technologies and equipment as well as lack of an effective quality management system. To ensure consistent supply of safe, effective and high-quality drug products available to the patients, the U.S. Food and Drug Administration (FDA) supports modernizing pharmaceutical manufacturing for improvements in product quality. Specifically, five new initiatives are proposed here to achieve this goal. They include: (i) advancing regulatory science for pharmaceutical manufacturing; (ii) establishing a public-private institute for pharmaceutical manufacturing innovation; (iii) creating incentives for investment in the technological upgrade of manufacturing processes and facilities; (iv) leveraging external expertise for regulatory quality assessment of emerging technologies; and (v) promoting the international harmonization of approaches for expediting the global adoption of emerging technologies. PMID- 27260135 TI - Formulation and characterization of a 0.1% rapamycin cream for the treatment of Tuberous Sclerosis Complex-related angiofibromas. AB - Medicines for the treatment of rare diseases frequently do not attract the interest of the pharmaceutical industry, and hospital pharmacists are thus often requested by physicians to prepare personalized medicines. Tuberous Sclerosis Complex (TSC) is a rare disease that causes disfiguring lesions named facial angiofibromas. Various topical formulations of rapamycin (=sirolimus) have been proved effective in treating these changes in small case series. The present study provides for the first time characterization of a 0.1% rapamycin cream formulation presenting good rapamycin solubilisation. The first step of the formulation is solubilisation of rapamycin in Transcutol((r)), and the second step is the incorporation of the mixture in an oil-in-water cream. A HPLC stability-indicating method was developed. Rapamycin concentration in the cream was tested by HPLC and confirmed that it remained above 95% of the initial concentration for at least 85days, without characteristic degradation peaks. The preparation met European Pharmacopoeia microbial specifications throughout storage in aluminum tubes, including when patient use was simulated. Odour, appearance and colour of the preparation were assessed and no change was evidenced during storage. The rheological properties of the cream also remained stable throughout storage. To conclude, we report preparation of a novel cream formulation presenting satisfactory rapamycin solubilisation for the treatment of TSC cutaneous manifestations, with stability data. The cream is currently being used by our patients. Efficacy and tolerance will be reported later. PMID- 27260137 TI - Pregnant women are too cautious about risk of medicines. PMID- 27260136 TI - CCL2, but not its receptor, is essential to restrict immune privileged central nervous system-invasion of Japanese encephalitis virus via regulating accumulation of CD11b(+) Ly-6C(hi) monocytes. AB - Japanese encephalitis virus (JEV) is a re-emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2-CCL2 axis plays an important role in trafficking CD11b(+) Ly-6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2- and CCL2-ablated murine models. Somewhat surprisingly, the ablation of CCR2 and CCL2 resulted in starkly contrasting susceptibility to JE. CCR2 ablation induced enhanced resistance to JE, whereas CCL2 ablation highly increased susceptibility to JE. This contrasting regulation of JE progression by CCR2 and CCL2 was coupled to central nervous system (CNS) infiltration of Ly-6C(hi) monocytes and Ly-6G(hi) granulocytes. There was also enhanced expression of CC and CXC chemokines in the CNS of CCL2 ablated mice, which appeared to induce CNS infiltration of these cell populations. However, our data revealed that contrasting regulation of JE in CCR2 and CCL2-ablated mice was unlikely to be mediated by innate natural killer and adaptive T-cell responses. Furthermore, CCL2 produced by haematopoietic stem cell derived leucocytes played a dominant role in CNS accumulation of Ly-6C(hi) monocytes in infected bone marrow chimeric models, thereby exacerbating JE progression. Collectively, our data indicate that CCL2 plays an essential role in conferring protection against JE caused by JEV infection. In addition, blockage of CCR2, but not CCL2, will aid in the development of strategies for prophylactics and therapeutics of JE. PMID- 27260138 TI - Adrenal insufficiency in patients on long-term opioid analgesia. AB - OBJECTIVE: Opioid analgesia has been implicated as a cause of secondary adrenal insufficiency, but little is known of the prevalence of this potentially serious adverse effect in patients with chronic pain. DESIGN: Cross-sectional study of chronic pain patients on long-term opioid analgesia. PATIENTS: Patients attending tertiary chronic pain clinics at the Western General Hospital, Edinburgh, treated with long-term opioid analgesia (n = 48) with no recent exposure to exogenous glucocorticoids. RESULTS: Four patients (8.3%) had basal morning plasma cortisol concentrations below 100 nmol/l, of whom three failed to achieve a satisfactory cortisol response to exogenous ACTH1-24 stimulation (peak cortisol >430 nmol/l). Basal cortisol was positively associated with age (R = 0.398, P = 0.005) and negatively associated with BMI (R = -0.435, P = 0.002). CONCLUSIONS: Suppression of the hypothalamic-pituitary-adrenal axis is present in a clinically significant proportion of chronic pain patients treated with opioid analgesia. Studies of larger populations should be conducted to better define the prevalence and potential clinical consequences of adrenal insufficiency in this context. PMID- 27260139 TI - Recent developments in cyclodextrin functionalized monolithic columns for the enantioseparation of chiral drugs. AB - The use of monolithic supports containing cyclodextrins (CDs) or their derivatives as chiral stationary phases (CSPs) has drawn much attention in the field of enantioseparations. The present review summarized the recent developments in CD functionalized monolithic columns. After introducing their classification in Section 1, various strategies applied to the preparation of the three types of CD functionalized monoliths, i.e. silica based monoliths, organic polymer based monoliths and organic-silica based hybrid monoliths, are thoroughly summarized in Section 2. Particularly, three different preparation strategies for covalently immobilizing CDs onto monoliths, including multi-step strategy, single step strategy and one-pot strategy, are discussed. In the last section, the applications of CD functionalized monoliths in chiral separation of pharmaceuticals are highlighted. PMID- 27260140 TI - Marking of metabolites in the diagnostics of metabolic diseases and in the investigation of xenobiotics metabolism using NMR spectroscopy. AB - There are currently no sound estimates of the number of children born with a serious congenital disorder attributable to genetic or environmental causes (World Health Organization) but there is a supposed number of babies born with birth defects per year: in the world approximately 7.9 million children (6% of births). There is conducted population-based screening by the individual countries. The specialised methods are used when it is not possible to diagnose disease in screening. In recent years in the diagnostics of these disorders the methods of Magnetic Resonance Spectroscopy of the brain (in vivo1H-MRS) and high resolution NMR spectroscopy gain in importance. The manuscript focused on developing the method of marking the metabolic diseases markers of various origins using NMR spectroscopy (including synthesis of markers). Considering the disorders occurring among children, according to Hoffman, Zschocke, Nyhan, there are three following groups of inherited metabolic diseases: disorders of intermediary metabolism, disorders of the biosynthesis and breakdown of complex molecules and neurotransmitter defects and related disorders. The presented investigation is focused on: a study of selected compounds that cause disorders of intermediary metabolism, a study of compounds that cause disorders of the biosynthesis and breakdown of complex molecules and a study of compounds that cause neurotransmitter defects and related disorders. In the subsequent chapter of manuscript there are presented the results of investigation concerning the metabolism of xenobiotics that could potentially be used in therapy of inherited metabolic diseases, basing on stilbene derivatives. In the last chapter there are presented the results of experiments with creatinine- the metabolite produced in muscles. PMID- 27260141 TI - The B-cell response to foot-and-mouth-disease virus in cattle following vaccination and live-virus challenge. AB - Antibodies play a pivotal role against viral infection, and maintenance of protection is dependent on plasma and memory B-cells. Understanding antigen specific B-cell responses in cattle is essential to inform future vaccine design. We have previously defined T-cell-dependent and -independent B-cell responses in cattle, as a prelude to investigating foot-and-mouth-disease-virus (FMDV) specific B-cell responses. In this study, we have used an FMDV O-serotype vaccination (O1-Manisa or O SKR) and live-virus challenge (FMDV O SKR) to investigate the homologous and heterologous B-cell response in cattle following both vaccination and live-virus challenge. The FMDV O-serotype vaccines were able to induce a cross-reactive plasma-cell response, specific for both O1-Manisa and O SKR, post-vaccination. Post-FMDV O SKR live-virus challenge, the heterologous O1-Manisa vaccination provided cross-protection against O SKR challenge and cross reactive O SKR-specific plasma cells were induced. However, vaccination and live virus challenge were not able to induce a detectable FMDV O-serotype-specific memory B-cell response in any of the cattle. The aim of new FMDV vaccines should be to induce memory responses and increased duration of immunity in cattle. PMID- 27260142 TI - Leishmania infantum-specific production of IFN-gamma and IL-10 in stimulated blood from dogs with clinical leishmaniosis. AB - BACKGROUND: There is limited information available on cytokine profiles in dogs with different degrees of disease severity due to natural infection of Leishmania infantum. The aim of this study was to investigate L. infantum-specific IFN-gamma and IL-10 production in blood from dogs with leishmaniosis at diagnosis and correlate these findings with disease severity, humoral immune response and blood parasitemia. METHODS: Sixty dogs were diagnosed based on physical examination, routine laboratory tests, L. infantum-specific antibody levels measured by quantitative ELISA and blood parasitemia by real-time PCR. Heparin whole blood was stimulated with L. infantum soluble antigen (LSA) and concanavalin A (ConA) and incubated for 5 days. IFN-gamma and IL-10 concentrations were measured in supernatants with sandwich ELISAs. RESULTS: The majority of dogs (n = 36) were classified as LeishVet stage II (moderate disease). The rest of the dogs were classified as stage I (n = 10), III (n = 10) and IV (n = 4). Dogs classified with stage I and IIa presented significantly higher (P = 0.02) LSA IFN-gamma concentrations, lower (P <0.0001) antibody levels and a tendency for lower blood parasitemia (P = 0.1) than dogs classified with stages IIb, III or IV while no differences in ConA IFN-gamma or IL-10 concentrations were observed among groups. Thirty-five dogs produced significantly higher LSA IFN-gamma (mean +/- SD: 2320 +/- 3960 pg/ml) and ConA IFN-gamma (mean +/- SD: 7887 +/- 7273 pg/ml) when compared with 25 dogs that did not produce detectable LSA IFN-gamma but produced ConA IFN-gamma (mean +/- SD: 4917 +/- 5233 pg/ml). IFN-gamma producer dogs presented lower (mean +/- SD: 5750 +/- 14,082 ELISA units (EU), P = 0.001) antibody levels and blood parasitemia (mean +/- SD: 5 +/- 10 parasites/ml, P = 0.001) when compared with IFN-gamma non-producers (mean +/- SD: 19,638 +/- 28,596 EU and 1100 +/- 5112 parasites/ml), respectively. LSA IL-10 was not detectable in 34 dogs while 49 dogs secreted ConA IL-10 (mean +/- SD of 90 +/- 103 pg/ml). LSA IFN-gamma concentration was negatively correlated with blood parasitemia and antibody levels and positively correlated with ConA IFN-gamma and LSA IL-10 concentrations. CONCLUSIONS: The results of this study demonstrate that sick dogs lacking L. infantum specific IFN-gamma production in stimulated whole blood produce a strong humoral response, have a high blood parasitemia and severe clinical disease. IL-10 does not appear to be a marker of disease severity. PMID- 27260143 TI - Enterococcus Xinjiangensis sp. nov., Isolated from Yogurt of Xinjiang, China. AB - A Gram-strain-positive bacterial strain 48(T) was isolated from traditional yogurt in Xinjiang Province, China. The bacterium was characterized by a polyphasic approach, including 16S rRNA gene sequence analysis, polymerase alpha subunit (rpoA) gene sequence analysis, determination of DNA G+C content, DNA-DNA hybridization with the type strain of Enterococcus ratti and analysis of phenotypic features. Strain 48(T) accounted for 96.1, 95.8, 95.8, and 95.7 % with Enterococcus faecium CGMCC 1.2136(T), Enterococcus hirae ATCC 9790(T), Enterococcus durans CECT 411(T), and E. ratti ATCC 700914(T) in the 16S rRNA gene sequence similarities, respectively. The sequence of rpoA gene showed similarities of 99.0, 96.0, 96.0, and 96 % with that of E. faecium ATCC 19434(T), Enterococcus villorum LMG12287, E. hirae ATCC 9790(T), and E. durans ATCC 19432(T), respectively. Based upon of polyphasic characterization data obtained in the study, a novel species, Enterococcus xinjiangensis sp. nov., was proposed and the type strain was 48(T)(=CCTCC AB 2014041(T) = JCM 30200(T)). PMID- 27260144 TI - Changes in Corneal Densitometry in Patients with Fuchs Endothelial Dystrophy after Endothelial Keratoplasty. AB - PURPOSE: The aim of the study was to quantify corneal densitometry in patients with Fuchs endothelial dystrophy (FED) after endothelial keratoplasty. MATERIALS AND METHODS: We retrospectively reviewed the charts and anterior segment data of patients with FED before and after endothelial keratoplasty. Patients were examined using the Scheimpflug-based Oculus Pentacam corneal densitometry module. Densitometry parameters in different corneal layers and in different annuli were extracted and analyzed. RESULTS: 27 eyes of 27 patients after endothelial keratoplasty (11 DSAEK, 16 DMEK) were included. After endothelial keratoplasty the total corneal light backscatter at total corneal thickness in the central cornea (0-2 mm annulus) was significantly lower than before (DSAEK: p = 0.026, DMEK: p = 0.001). In the entire group the total corneal light backscatter at total corneal thickness and at total diameter before surgery correlated with the postoperative values (Pearson correlation = 0.49, p = 0.01). The strongest correlation was found in the central layer in the DMEK group (Pearson correlation = 0.79, p < 0.001). CONCLUSIONS: Corneal densitometry is a useful, objective method for quantification of the outcome of posterior lamellar keratoplasty irrespective of visual acuity. There is a significant correlation between preoperative and postoperative corneal light backscatter values after endothelial keratoplasty, especially in the case of the DMEK procedure. PMID- 27260145 TI - The Contribution of Diabetes Education in the Treatment of People with Type 2 Diabetes and Risk of Cardiovascular Disease. AB - Diabetes has caused 5.1 million deaths, primarily from cardiovascular disease. Large clinical studies have proven the importance of intensive control of diabetes from diagnosis to prevent microvascular and macrovascular complications of the disease in the long term. Diabetes education conducted by an interdisciplinary team of doctors, nurses, nutritionists, psychologists, and others is a necessary tool to ensure effective behavioral change and help overcome the obstacles that may hinder self care. Several studies have been analyzed in this review, in which we find a variety of results. Diabetes education has proven to be essential to patient compliance with their T2DM treatment; the main objective is to prevent acute and chronic complications, especially cardiovascular ones, which are the main causes of mortality. PMID- 27260146 TI - Duration of Dual Antiplatelet Therapy in Coronary Artery Disease: a Review Article. AB - Dual antiplatelet therapy (DAPT) following an acute coronary syndrome or after placement of a coronary artery stent is superior to aspirin alone for prevention of atherothrombotic events but carries an increased bleeding risk. DAPT should be continued for at least 12 months based on current guidelines. Recent randomized trials demonstrate reduced ischemic events including myocardial infarction (MI), stroke, and death with continued DAPT for up to 30 months or longer, particularly in the post-MI population. However, this clinical benefit is accompanied by an increased risk of bleeding. Additional trials show mixed safety and efficacy with duration of DAPT of less than 12 months. The current data emphasizes the need to individualize DAPT duration at the patient level to balance the clinical benefits of a reduced risk of cardiovascular ischemic events with the greater risk of clinically significant bleeding. Patients at an increased risk of ischemic events and a lower risk of bleeding should be strongly considered for prolonged DAPT beyond the 1 year currently recommended in the practice guidelines. PMID- 27260147 TI - Nephrotic Syndrome Associated with Multicystic Kidney Disease with Concomitant Cerebral Venous Thrombosis. PMID- 27260148 TI - Ileus and Intra-Abdominal Hypertension due to Phosphate- Containing Enema. AB - The most well known complications of fleet enema solution are cardiac insufficiency, renal failure, water-electrolyte imbalance, and ileus. A 7-y-old girl with phenylketonuria and long-term constipation was admitted to the emergency department with symptoms of seizure, vomiting and abdominal distention. Laboratory results revealed hypocalcemia and hyperphosphatemia. ECG findings showed normal sinus rhythm and prolonged QT interval. At the follow-up, the patient's abdominal distention was markedly increased. She was evaluated for a surgical pathology and, this was considered unlikely. Intra-abdominal pressure (IAP) was 19.5 mmHg. Gastric and colonic decompression, intravenous 10 % calcium gluconate were applied. After 2 d of treatment, the patient's condition became stable, and serum calcium and phosporus normalized to 8.8 mg/dl and 4.0 mg/dl, respectively. Abdominal distention regressed and the last IAP measurement was 3.5 mmHg. Thus, IAP measurements are a useful adjunct in clinical follow-up of patients with progressive abdominal distention due to phosphate enema use. PMID- 27260150 TI - Clopidogrel Markedly Increases Plasma Concentrations of CYP2C8 Substrate Pioglitazone. AB - The glucose-lowering drug pioglitazone undergoes hepatic CYP2C8-mediated biotransformation to its main metabolites. The antiplatelet drug clopidogrel is metabolized to clopidogrel acyl-beta-d-glucuronide, which was recently found to be a strong time-dependent inhibitor of CYP2C8 in humans. Therefore, we studied the effect of clopidogrel on the pharmacokinetics of pioglitazone. In a randomized crossover study, 10 healthy volunteers ingested either 300 mg of clopidogrel on day 1, and 75 mg on days 2 and 3, or placebo. Pioglitazone 15 mg was administered 1 hour after placebo and clopidogrel on day 1. Plasma concentrations of pioglitazone, clopidogrel, and their main metabolites were measured up to 72 hours. Clopidogrel increased the area under the plasma concentration-time curve (AUC0-infinity) of pioglitazone 2.1-fold [P < 0.001, 90% confidence interval (CI) 1.8-2.6] and prolonged its half-life from 6.7 to 11 hours (P = 0.002). The peak concentration of pioglitazone was unaffected but the concentration at 24 hours was increased 4.5-fold (range 1.6-9.8; P < 0.001, 90% CI 3.17-6.45) by clopidogrel. The M-IV-to-pioglitazone AUC0-infinity ratio was 49% (P < 0.001, 90% CI 0.40-0.59) of that during the control phase, indicating that clopidogrel inhibited the CYP2C8-mediated biotransformation of pioglitazone. Clopidogrel increases the exposure to pioglitazone by inhibiting its CYP2C8 mediated biotransformation. In consequence, use of clopidogrel may increase the risk of fluid retention and other concentration-related adverse effects of pioglitazone. PMID- 27260149 TI - Comparison of Intranasal Dexmedetomidine with Intranasal Clonidine as a Premedication in Surgery. AB - OBJECTIVES: To compare effectiveness of intranasal dexmedetomidine and clonidine as anxiolytics and sedatives in pediatric patients undergoing various surgeries. METHODS: This double blind randomized placebo controlled study was conducted on 105 surgical patients of American Society of Anesthesiologist (ASA) physical status I-II, aged between 2 and 9 y in a tertiary-care hospital (February 2014 to September 2015). Participants were randomly allocated to three groups to receive either intranasal dexmedetomidine 2 MUg/kg (Group I) or intranasal clonidine 3 MUg/kg (Group II) or intranasal saline 0.5 ml (Group III). The primary outcome measure was proportion of patients with satisfactory anxiolysis and sedation at 30 min after drug administration. Secondary outcome measures included time taken to achieve Aldrete score of 9 and number of doses of rescue analgesia required in 12 h after surgery. RESULTS: Satisfactory anxiolysis was achieved by 88.5% in Group I vs. 60% in Group II (p = 0.001) and satisfactory sedation by 57.1% in Group I vs. 25.7% in Group II (p = 0.001) 30 min after premedication. Rescue analgesia requirement was significantly less in Group I as compared to Group II (p = 0.001) while time taken to achieve Aldrete score was comparable between the study groups (p = 0.185). CONCLUSIONS: Intranasal dexmedetomidine is a better anxiolytic and sedative as compared to clonidine. Postoperative analgesic requirement was also significantly decreased after intranasal dexmedetomidine. Thus, it can be preferred as compared to clonidine for premedication in pediatric surgical patients. PMID- 27260151 TI - A Pharmacokinetic Modeling Approach to Predict the Contribution of Active Metabolites to Human Efficacious Dose. AB - A preclinical drug candidate, MRK-1 (Merck candidate drug parent compound), was found to elicit tumor regression in a mouse xenograft model. Analysis of samples from these studies revealed significant levels of two circulating metabolites, whose identities were confirmed by comparison with authentic standards using liquid chromatography-tandem mass spectrometry. These metabolites were found to have an in vitro potency similar to that of MRK-1 against the pharmacological target and were therefore thought to contribute to the observed efficacy. To predict this contribution in humans, a pharmacokinetic (PK) modeling approach was developed. At the mouse efficacious dose, the areas under the plasma concentration time curves (AUCs) of the active metabolites were normalized by their in vitro potency compared with MRK-1. These normalized metabolite AUCs were added to that of MRK-1 to yield a composite efficacious unbound AUC, expressed as "parent drug equivalents," which was used as the target AUC for predictions of the human efficacious dose. In vitro and preclinical PK studies afforded predictions of the PK of MRK-1 and the two active metabolites in human as well as the relative pathway flux to each metabolite. These were used to construct a PK model (Berkeley Madonna, version 8.3.18; Berkeley Madonna Inc., University of California, Berkeley, CA) and to predict the human dose required to achieve the target parent equivalent exposure. These predictions were used to inform on the feasibility of the human dose in terms of size, frequency, formulation, and likely safety margins, as well as to aid in the design of preclinical safety studies. PMID- 27260152 TI - Moebius syndrome: clinical features, diagnosis, management and early intervention. AB - BACKGROUND: Moebius syndrome (MBS) is rare disease characterized by nonprogressive congenital uni- or bi-lateral facial (i. e. VII cranial nerve) and abducens (i. e. VI cranial nerve) palsy. Although the neurological and ophthalmological findings are quite well-known, data concerning the attendant functional difficulties and their changes over time are seldom addressed. In this study we attempt to estimate the prevalence of clinical and functional data in an Italian cohort affected by MBS. METHODS: The study included 50 children, 21 males and 29 females, aged 1 month to 14 years. The patients entered into a multidisciplinary diagnostic and follow-up protocol that had the specific purpose of detecting clinical and developmental deficits related to MBS. RESULTS: Involvement of the VII cranial nerve (total/partial, bilateral or unilateral) was present in 96 % of patients, and of the VI nerve in 85 %. Two patients were without impairment of the VII nerve and seven patients had no involvement of the VI nerve and were thus classified as Moebius-like because of the involvement of other CNs. Additional affected CNs were numbers III-IV in 16 %, V in 11 %, VIII and X each in 8 %, the XI in 6 %, the IX, most often partially, in 22 %, and the XII in 48 % of cases. Their development was characterized by global delay at one year of age, motor, emotional and speech difficulties at two years of age, a trend toward normalization at three years of age but with weakness in hand-eye coordination, and achieving average results at five years of age. Overall 90 % of children had a normal developmental quotient whereas only 10 % manifested cognitive deficits. CONCLUSION: Early rehabilitation may enhance the recovery of normal function, particularly in vulnerable areas of development. It is possible that early intervention that integrates sensory and visual information with emotional difficulties can improve the prognosis of the child with MBS. PMID- 27260153 TI - Differences in maternal responsive and directive behavior during free play with and without aided AAC. AB - Maternal directive and responsive behaviors were compared for 25 mothers and children with complex communication needs using two types of toys (familiar and unfamiliar toys). Each type of toy play was conducted with and without a single message speech-generating communication device (SGD) programmed to say "more." Rate percentages of coded intervals for maternal directive and responsive behaviors were analyzed using repeated measures ANOVAs. Results indicated that mothers used significantly more responsive behaviors when playing with their own familiar toys than with unfamiliar toys, but no differences in directiveness between types of play. Mothers showed no differences in responsivity or directiveness when the SGD was added to play interactions, indicating that the SGD did not introduce task features that detracted from the mothers' existing levels of responsivity with their children. Clinical implications are discussed. PMID- 27260154 TI - Functional Role of Bacteria from Invasive Phragmites australis in Promotion of Host Growth. AB - We hypothesize that bacterial endophytes may enhance the competitiveness and invasiveness of Phragmites australis. To evaluate this hypothesis, endophytic bacteria were isolated from P. australis. The majority of the shoot meristem isolates represent species from phyla Firmicutes, Proteobacteria, and Actinobacteria. We chose one species from each phylum to characterize further and to conduct growth promotion experiments in Phragmites. Bacteria tested include Bacillus amyloliquefaciens A9a, Achromobacter spanius B1, and Microbacterium oxydans B2. Isolates were characterized for known growth promotional traits, including indole acetic acid (IAA) production, secretion of hydrolytic enzymes, phosphate solubilization, and antibiosis activity. Potentially defensive antimicrobial lipopeptides were assayed for through application of co-culturing experiments and mass spectrometer analysis. B. amyloliquefaciens A9a and M. oxydans B2 produced IAA. B. amyloliquefaciens A9a secreted antifungal lipopeptides. Capability to promote growth of P. australis under low nitrogen conditions was evaluated in greenhouse experiments. All three isolates were found to increase the growth of P. australis under low soil nitrogen conditions and showed increased absorption of isotopic nitrogen into plants. This suggests that the Phragmites microbes we evaluated most likely promote growth of Phragmites by enhanced scavenging of nitrogenous compounds from the rhizosphere and transfer to host roots. Collectively, our results support the hypothesis that endophytic bacteria play a role in enhancing growth of P. australis in natural populations. Gaining a better understanding of the precise contributions and mechanisms of endophytes in enabling P. australis to develop high densities rapidly could lead to new symbiosis-based strategies for management and control of the host. PMID- 27260155 TI - Searching for a Mate: Pheromone-Directed Movement of the Benthic Diatom Seminavis robusta. AB - Diatoms are species-rich microalgae that often have a unique life cycle with vegetative cell size reduction followed by size restoration through sexual reproduction of two mating types (MT(+) and MT(-)). In the marine benthic diatom Seminavis robusta, mate-finding is mediated by an L-proline-derived diketopiperazine, a pheromone produced by the attracting mating type (MT(-)). Here, we investigate the movement patterns of cells of the opposite mating type (MT(+)) exposed to a pheromone gradient, using video monitoring and statistical modeling. We report that cells of the migrating mating type (MT(+)) respond to pheromone gradients by simultaneous chemotaxis and chemokinesis. Changes in movement behavior enable MT(+) cells to locate the direction of the pheromone source and to maximize their encounter rate towards it. PMID- 27260156 TI - Genomic Copy Number Dictates a Gene-Independent Cell Response to CRISPR/Cas9 Targeting. AB - The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G2 cell cycle arrest. By examining single-guide RNAs that map to multiple genomic sites, we found that this cell response to CRISPR/Cas9 editing correlated strongly with the number of target loci. These observations indicate that genome targeting by CRISPR/Cas9 elicits a gene-independent antiproliferative cell response. This effect has important practical implications for the interpretation of CRISPR/Cas9 screening data and confounds the use of this technology for the identification of essential genes in amplified regions. SIGNIFICANCE: We found that the number of CRISPR/Cas9-induced DNA breaks dictates a gene-independent antiproliferative response in cells. These observations have practical implications for using CRISPR/Cas9 to interrogate cancer gene function and illustrate that cancer cells are highly sensitive to site-specific DNA damage, which may provide a path to novel therapeutic strategies. Cancer Discov; 6(8); 914-29. (c)2016 AACR.See related commentary by Sheel and Xue, p. 824See related article by Munoz et al., p. 900This article is highlighted in the In This Issue feature, p. 803. PMID- 27260163 TI - Anthrax Edema Factor: An Ion-Adaptive Mechanism of Catalysis with Increased Transition-State Conformational Flexibility. AB - Edema Factor (EF) is one of three major toxins of anthrax. EF is an adenylyl cyclase that disrupts cell signaling by accelerating the conversion of ATP into cyclic-AMP. EF has a much higher catalytic rate than that of mammalian adenylyl cyclases (mACs). Crystal structures were obtained for mACs and EF, but the molecular basis for different catalytic activities remained poorly understood. In particular, the arrangement of the active site in EF is unclear in what concerns the number of ions present and the conformation of the substrate. Here, we use quantum mechanics-molecular mechanics simulations to estimate the free-energy profiles for the reaction catalyzed by EF and a mAC. We found that EF catalysis is possible, and faster than that of mACs, in both one and two Mg(2+)-ion-binding modes, providing adaptive plasticity to host-cell environments. In both enzymes, the reaction mechanisms are highly associative. However, mechanistic differences exist. In the mAC, the nucleophile oxygen (ATP-O3') is consistently coordinated to one of the Mg(2+) ions, increasing its acidity. In EF, on the other hand, this coordination is eventual and not essential for the reaction to proceed. The persistent coordination of O3' to the ion is favored in mACs by a greater ion partial charge. In EF, the reduced acidity of the O3' oxygen is compensated by the presence of the His351 residue for proton abstraction. As proton transfer in EF does not require persistent attachment of the substrate to an ion, the substrate (ATP) and transition state display greater conformational flexibilities. These greater flexibilities allow the sampling of lower-energy conformations and might represent an entropic advantage for catalytic efficiency. PMID- 27260157 TI - CRISPR Screens Provide a Comprehensive Assessment of Cancer Vulnerabilities but Generate False-Positive Hits for Highly Amplified Genomic Regions. AB - CRISPR/Cas9 has emerged as a powerful new tool to systematically probe gene function. We compared the performance of CRISPR to RNAi-based loss-of-function screens for the identification of cancer dependencies across multiple cancer cell lines. CRISPR dropout screens consistently identified more lethal genes than RNAi, implying that the identification of many cellular dependencies may require full gene inactivation. However, in two aneuploid cancer models, we found that all genes within highly amplified regions, including nonexpressed genes, scored as lethal by CRISPR, revealing an unanticipated class of false-positive hits. In addition, using a CRISPR tiling screen, we found that sgRNAs targeting essential domains generate the strongest lethality phenotypes and thus provide a strategy to rapidly define the protein domains required for cancer dependence. Collectively, these findings not only demonstrate the utility of CRISPR screens in the identification of cancer-essential genes, but also reveal the need to carefully control for false-positive results in chromosomally unstable cancer lines. SIGNIFICANCE: We show in this study that CRISPR-based screens have a significantly lower false-negative rate compared with RNAi-based screens, but have specific liabilities particularly in the interrogation of regions of genome amplification. Therefore, this study provides critical insights for applying CRISPR-based screens toward the systematic identification of new cancer targets. Cancer Discov; 6(8); 900-13. (c)2016 AACR.See related commentary by Sheel and Xue, p. 824See related article by Aguirre et al., p. 914This article is highlighted in the In This Issue feature, p. 803. PMID- 27260164 TI - Relation between Carcinoembryonic Antigen Levels in Colon Cancer Tissue and Serum Carcinoembryonic Antigen Levels at Initial Surgery and Recurrence. AB - OBJECTIVES: Carcinoembryonic antigen (CEA) is widely used for postoperative surveillance of colon cancer. Even if serum CEA is negative at initial surgery, it may turn positive at recurrence. We investigated the relation between serum CEA levels and the immunohistochemical staining status of CEA in the primary and resected metastatic tissues. METHODS: Out of 224 patients with recurrent colon cancer between 1998 and 2012, we studied 46 patients in whom serum CEA levels were measured and immunohistochemical staining for CEA was possible in the primary and metastatic tissues. RESULTS: The positive rate of serum CEA did not differ between initial surgery and recurrence, regardless of whether the cutoff value was set at 5 or 10 ng/ml (p = 0.829, p = 0.671). There was no relation between the CEA staining status and serum CEA level at initial surgery. However, the CEA staining status of metastatic tissue was significantly related to the serum CEA level at recurrence (p = 0.0046 and p = 0.0026). CONCLUSIONS: The immunohistochemical staining status of CEA in metastatic tissue is closely related to the serum CEA level. This finding suggests that serum CEA levels are influenced not only by the CEA production capacity of cancer cells but also by the ability of the surrounding tissue to release CEA into the blood. PMID- 27260165 TI - Letter to editor on "Efficiency of bimaxillary advancement surgery in increasing the volume of the upper airways: a systematic review of observational studies and meta-analysis". PMID- 27260167 TI - Dissecting the regulation of bile-induced biofilm formation in Staphylococcus aureus. AB - Aspiration of bile into the cystic fibrosis (CF) lung has emerged as a prognostic factor for reduced microbial lung biodiversity and the establishment of often fatal, chronic pathogen infections. Staphylococcus aureus is one of the earliest pathogens detected in the lungs of children with CF, and once established as a chronic infection, strategies for its eradication become limited. Several lung pathogens are stimulated to produce biofilms in vitro in the presence of bile. In this study, we further investigated the effects of bile on S. aureus biofilm formation. Most clinical S. aureus strains and the laboratory strain RN4220 were stimulated to form biofilms with sub-inhibitory concentrations of bovine bile. Additionally, we observed bile-induced sensitivity to aminoglycosides, which we exploited in a bursa aurealis transposon screen to isolate mutants reduced in aminoglycoside sensitivity and augmented in bile-induced biofilm formation. We identified five mutants that exhibited hypersensitivity to bile with respect to bile-induced biofilm formation, three of which carried transposon insertions within gene clusters involved in wall teichoic acid (WTA) biosynthesis or transport. Strain TM4 carried an insertion between the divergently oriented tagH and tagG genes, which encode the putative WTA membrane translocation apparatus. Ectopic expression of tagG in TM4 restored a wild-type bile-induced biofilm response, suggesting that reduced translocation of WTA in TM4 induced sensitivity to bile and enhanced the bile-induced biofilm formation response. We propose that WTA may be important for protecting S. aureus against exposure to bile and that bile-induced biofilm formation may be an evolved response to protect cells from bile-induced cell lysis. PMID- 27260166 TI - Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation. AB - BACKGROUND: Histamine is an amine widely known as a peripheral inflammatory mediator and as a neurotransmitter in the central nervous system. Recently, it has been suggested that histamine acts as an innate modulator of microglial activity. Herein, we aimed to disclose the role of histamine in microglial phagocytic activity and reactive oxygen species (ROS) production and to explore the consequences of histamine-induced neuroinflammation in dopaminergic (DA) neuronal survival. METHODS: The effect of histamine on phagocytosis was assessed both in vitro by using a murine N9 microglial cell line and primary microglial cell cultures and in vivo. Cells were exposed to IgG-opsonized latex beads or phosphatidylserine (PS) liposomes to evaluate Fcgamma or PS receptor-mediated microglial phagocytosis, respectively. ROS production and protein levels of NADPH oxidases and Rac1 were assessed as a measure of oxidative stress. DA neuronal survival was evaluated in vivo by counting the number of tyrosine hydroxylase positive neurons in the substantia nigra (SN) of mice. RESULTS: We found that histamine triggers microglial phagocytosis via histamine receptor 1 (H1R) activation and ROS production via H1R and H4R activation. By using apocynin, a broad NADPH oxidase (Nox) inhibitor, and Nox1 knockout mice, we found that the Nox1 signaling pathway is involved in both phagocytosis and ROS production induced by histamine in vitro. Interestingly, both apocynin and annexin V (used as inhibitor of PS-induced phagocytosis) fully abolished the DA neurotoxicity induced by the injection of histamine in the SN of adult mice in vivo. Blockade of H1R protected against histamine-induced Nox1 expression and death of DA neurons in vivo. CONCLUSIONS: Overall, our results highlight the relevance of histamine in the modulation of microglial activity that ultimately may interfere with neuronal survival in the context of Parkinson's disease (PD) and, eventually, other neurodegenerative diseases which are accompanied by microglia induced neuroinflammation. Importantly, our results also open promising new perspectives for the therapeutic use of H1R antagonists to treat or ameliorate neurodegenerative processes. PMID- 27260168 TI - Development of a measure (ICECAP-Close Person Measure) through qualitative methods to capture the benefits of end-of-life care to those close to the dying for use in economic evaluation. AB - BACKGROUND: End-of-life care affects both the patient and those close to them. Typically, those close to the patient are not considered within economic evaluation, which may lead to the omission of important benefits resulting from end-of-life care. AIM: To develop an outcome measure suitable for use in economic evaluation that captures the benefits of end-of-life care to those close to the dying. DESIGN: To develop the descriptive system for the outcome measure, in depth qualitative interviews were conducted with the participants and constant comparative analysis methods were used to develop a descriptive system for the measure. PARTICIPANTS: Twenty-seven individuals bereaved within the last 2 years or with a close-person currently receiving end-of-life care were purposively recruited into the study. Participants were recruited through newsletters, adverts, snowball sampling and a local hospice. RESULTS: Twenty-seven individuals were recruited. A measure of capability with six attributes, each with five levels, was developed based on themes arising from the analysis. Attributes comprise the following: good communication with services, privacy and space to be with the loved one, emotional support, practical support, being able to prepare and cope and being free from emotional distress related to the condition of the decedent. CONCLUSION: This measure is designed to capture the benefits of end-of life care to close-persons for use in economic evaluation. Further research should value the measure and develop methods for incorporating outcomes for close persons into economic evaluation. PMID- 27260169 TI - Advance care planning, palliative care, and end-of-life care interventions for homeless people: A systematic review. AB - BACKGROUND: Homeless individuals have a high prevalence of multiple chronic comorbidities and early mortality compared to the general population. They also experience significant barriers to access and stigmatization in the healthcare system. Providing advance care planning, palliative care, and end-of-life care for this underserved population is an important health issue. AIM: To summarize and evaluate the evidence surrounding advance care planning, palliative care, and end-of-life care interventions for homeless persons. DESIGN: A systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. DATA SOURCES: Articles from MEDLINE, EMBASE, CINAHL, PsycINFO, Social Work Abstracts, Cochrane Library, Web of Science, and PubMed databases were searched through 13 June 2015. Peer-reviewed studies that implemented advance care planning, palliative care, and end-of-life care interventions for homeless populations were included. Data from studies were independently extracted by two investigators using pre-specified criteria, and quality was assessed using modified Cochrane and Critical Appraisal Skills Programme tools. RESULTS: Six articles met inclusion criteria. Two studies were randomized controlled trials involving advance directive completion. Two cohort studies investigated the costs of a shelter-based palliative care intervention and predictors for completing advance directives. These studies were rated low to fair quality. Two qualitative studies explored the interface between harm-reduction services and end-of-life care and the conditions for providing palliative care for homeless persons in a support home. CONCLUSION: The effectiveness of advance care planning, palliative care, and end-of-life care interventions for homeless individuals is uncertain. High-quality studies of interventions that reflect the unique and complex circumstances of homeless populations and investigate patient-related outcomes, caregiver burden, and cost-effectiveness are needed. PMID- 27260171 TI - Venturing out safely: The biogeography of Homo erectus dispersal out of Africa. AB - The dispersal of Homo erectus out of Africa at some 1.9 million years ago is one of the most important, crucial, and yet controversial events in human evolution. Current opinions about this episode expose the contrast between those who see H. erectus as a highly social, cooperative species seeking out new ecological opportunities to exploit, and those preferring a passive, climate driven explanation for such an event. By using geostatistics techniques and probabilistic models, we characterised the ecological context of H. erectus dispersal, from its East African origin to the colonization of Eurasia, taking into account both the presence of other large mammals and the physical characteristics of the landscape as potential factors. Our model indicated that H. erectus followed almost passively the large herbivore fauna during its dispersal. In Africa, the dispersal was statistically associated with the presence of large freshwater bodies (Rift Valley Lakes). In Eurasia, the presence of H. erectus was associated with the occurrence of geological outcrops likely yielding unconsolidated flint. During the early phase of dispersal, our model indicated that H. erectus actively avoided areas densely populated by large carnivores. This pattern weakened as H. erectus dispersed over Europe, possibly because of the decreasing presence of carnivores there plus the later acquisition of Acheulean technology. During this later phase, H. erectus was associated with limestone and shaley marl, and seems to have been selecting for high-elevation sites. While our results do not directly contradict the idea that H. erectus may have been an active hunter, they clearly point to the fact that predator avoidance may have conditioned its long-distance diffusion as it moved outside Africa. The modelled dispersal route suggests that H. erectus remained preferentially associated with low/middle latitude (i.e., comparatively warm) sites throughout its colonization history. PMID- 27260170 TI - External Validation and Update of a Prediction Rule for the Duration of Sickness Absence Due to Common Mental Disorders. AB - Purpose The objective of the present study was to validate an existing prediction rule (including age, education, depressive/anxiety symptoms, and recovery expectations) for predictions of the duration of sickness absence due to common mental disorders (CMDs) and investigate the added value of work-related factors. Methods A prospective cohort study including 596 employees who reported sick with CMDs in the period from September 2013 to April 2014. Work-related factors were measured at baseline with the Questionnaire on the Experience and Evaluation of Work. During 1-year follow-up, sickness absence data were retrieved from an occupational health register. The outcome variables of the study were sickness absence (no = 0, yes = 1) at 3 and 6 months after reporting sick with CMDs. Discrimination between workers with and without sickness absence was investigated at 3 and 6 months with the area under the receiver operating characteristic curve (AUC). Results A total of 220 (37 %) employees agreed to participate and 211 (35 %) had complete data for analysis. Discrimination was poor with AUC = 0.69 and AUC = 0.55 at 3 and 6 months, respectively. When 'variety in work' was added as predictor variable, discrimination between employees with and without CMD sickness absence improved to AUC = 0.74 (at 3 months) and AUC = 0.62 (at 6 months). Conclusions The original prediction rule poorly predicted CMD sickness absence duration. After adding 'variety in work', the prediction rule discriminated between employees with and without CMD sickness absence 3 months after reporting sick. This new prediction rule remains to be validated in other populations. PMID- 27260172 TI - The Chatelperronian conundrum: Blade and bladelet lithic technologies from Quincay, France. AB - The discovery of an almost complete Neanderthal skeleton in a Chatelperronian context at Saint-Cesaire 35 years ago changed our perspective on the beginning of the Upper Paleolithic in western Europe. Since then, the Chatelperronian has generally been considered a "transitional" industry rather than an Upper or a Middle Paleolithic industry because of its chronological position, and the association of Neanderthal remains with blades, bone tools and personal ornaments. Several competing hypotheses have been proposed to explain the association between Neanderthals and these types of artefacts including post depositional mixing, acculturation from anatomically modern human populations, or an independent technological evolution by local Neanderthal populations. Quincay Cave is the only Chatelperronian site where personal ornaments have been found that does not contain an overlying Upper Paleolithic layer. This means that the post-depositional mixing of later elements into the Chatelperronian may not be used as an explanation for the presence of these materials. We report here on a detailed technological analysis of lithic artefacts from the three Chatelperronian layers at Quincay Cave. We compare our results with the technology of Mousterian blade industries dating to OIS (oxygen isotope stage) 5, the Mousterian of Acheulian Tradition type B, and the Proto-Aurignacian. We show that the Chatelperronian is sufficiently divergent from the Middle Paleolithic to be classified as a fully Upper Paleolithic industry, with a focus on blade and bladelet production. We also show that the Quincay Chatelperronian includes retouched bladelets that resemble those found in the Proto-Aurignacian, but were produced in a different manner. We argue that a technological convergence cannot account for these behaviors, since the specific type of retouched bladelet associated with the Chatelperronian was also regularly used by Proto-Aurignacian of neighboring regions. We suggest that the idea of retouched bladelets may have diffused from the northern Proto-Aurignacian to the Quincay Chatelperronian and that the transmission of the morphology of this desired end-product without the transmission of its manufacturing process may point toward a low degree of social intimacy between these groups. We conclude that the apparent paradox of the Chatelperronian is the result of the complexity of interaction between Neanderthal and anatomically modern human groups in western Europe between 45,000 and 40,000 years ago. PMID- 27260173 TI - Hominin teeth from the Middle Pleistocene site of Yiyuan, Eastern China. AB - In 1981-1982, some hominin fossils, including a relatively complete skull and seven isolated teeth, were recovered from the Middle Pleistocene site of Yiyuan in Eastern China. In the present study we provide a detailed metric and morphological comparison of the Yiyuan dental sample in order to characterize better the variability of the human populations that inhabited China during the Middle Pleistocene. Aside from taxonomic and phylogenetic questions, the lack of understanding and/or knowledge about the morphological variability of these populations have caused concern about the human versus non-human nature of some of the hominin dental remains found in East Asia during the Early and the Middle Pleistocene. Thus, our study aims to present a detailed description and comparison of the Yiyuan isolated teeth to 1) discuss and support their human nature and 2) to explore their taxonomic affinities with regard to other penecontemporaneous populations from Asia. Our results clearly differentiate the Yiyuan sample from Pongo specimens and support a human attribution for the Yiyuan material. Our analyses also suggest that the Yiyuan teeth form a morphologically coherent group together with samples from Zhoukoudian, Chaoxian and Hexian. They are different from the more derived specimens from Panxian Dadong, suggesting a pattern of biogeographic isolation and different evolutionary trends between northern and southern China during the Middle Pleistocene. In addition, and despite sharing a common morphological bauplan with Homo erectus sensu stricto (s.s.), the Yiyuan, Zhoukoudian and Hexian teeth are also different from the Indonesian Early Pleistocene samples. In particular, the expression of a highly crenulated or dendritic enamel-dentine surface could be unique to these groups. Our study supports the notion that the taxonomy of the Pleistocene hominins from Asia may have been oversimplified. Future studies should explore the variability of the Asian specimens and reconsider whether all the samples can be attributed to H. erectus s.s. PMID- 27260174 TI - Adult Neandertal clavicles from the El Sidron site (Asturias, Spain) in the context of Homo pectoral girdle evolution. AB - We undertook a three-dimensional geometric morphometric (3DGM) analysis on 12 new Neandertal clavicle specimens from the El Sidron site (Spain), dated to 49,000 years ago. The 3DGM methods were applied in a comparative framework in order to improve our understanding of trait polarity in features related to Homo pectoral girdle evolution, using other Neandertals, Homo sapiens, Pan, ATD6-50 (Homo antecessor), and KNM-WT 15000 (Homo ergaster/erectus) in the reference collection. Twenty-nine homologous landmarks were measured for each clavicle. Variation and morphological similarities were assessed through principal component analysis, conducted separately for the complete clavicle and the diaphysis. On average, Neandertal clavicles had significantly larger muscular entheses, double dorsal curvature, clavicle torsion, and cranial orientation of the acromial end than non-Neandertal clavicles; the El Sidron clavicles fit this pattern. Variation within the samples was large, with extensive overlap between Homo species; only chimpanzee specimens clearly differed from the other specimens in morphometric terms. Taken together, our morphometric analyses are consistent with the following phylogenetic sequence. The primitive condition of the clavicle is manifest in the cranial orientation of both the acromial and sternal ends. The derived condition expressed in the H. sapiens + Neandertal clade is defined by caudal rotation of both the sternal and acromial ends, but with variation in the number of acromia remaining in a certain cranial orientation. Finally, the autapomorphic Neandertal condition is defined by secondarily acquired primitive cranial re-orientation of the acromial end, which varies from individual to individual. These results suggest that the pace of phylogenetic change in the pectoral girdle does not seem to follow that of other postcranial skeletal features. PMID- 27260175 TI - Geographic variation in gorilla limb bones. AB - Gorilla systematics has received increased attention over recent decades from primatologists, conservationists, and paleontologists. Studies of geographic variation in DNA, skulls, and teeth have led to new taxonomic proposals, such as recognition of two gorilla species, Gorilla gorilla (western gorilla) and Gorilla beringei (eastern gorilla). Postcranial differences between mountain gorillas (G. beringei beringei) and western lowland gorillas (G. g. gorilla) have a long history of study, but differences between the limb bones of the eastern and western species have not yet been examined with an emphasis on geographic variation within each species. In addition, proposals for recognition of the Cross River gorilla as Gorilla gorilla diehli and gorillas from Tshiaberimu and Kahuzi as G. b. rex-pymaeorum have not been evaluated in the context of geographic variation in the forelimb and hindlimb skeletons. Forty-three linear measurements were collected from limb bones of 266 adult gorillas representing populations of G. b. beringei, Gorilla beringei graueri, G. g. gorilla, and G. g. diehli in order to investigate geographic diversity. Skeletal elements included the humerus, radius, third metacarpal, third proximal hand phalanx, femur, tibia, calcaneus, first metatarsal, third metatarsal, and third proximal foot phalanx. Comparisons of means and principal components analyses clearly differentiate eastern and western gorillas, indicating that eastern gorillas have absolutely and relatively smaller hands and feet, among other differences. Gorilla subspecies and populations cluster consistently by species, although G. g. diehli may be similar to the eastern gorillas in having small hands and feet. The subspecies of G. beringei are distinguished less strongly and by different variables than the two gorilla species. Populations of G. b. graueri are variable, and Kahuzi and Tshiaberimu specimens do not cluster together. Results support the possible influence of higher-altitude Pleistocene refugia on patterns of geographic variation in gorillas. PMID- 27260176 TI - The age of three Middle Palaeolithic sites: Single-grain optically stimulated luminescence chronologies for Pech de l'Aze I, II and IV in France. AB - Optically stimulated luminescence (OSL) measurements were made on individual, sand-sized grains of quartz from Middle Palaeolithic deposits at three sites (Pech de l'Aze I, II and IV) located close to one another in the Dordogne region of southwest France. We were able to calculate OSL ages for 69 samples collected from these three sites. These ages reveal periods of occupation between about 180 and 50 thousand years ago. Our single-grain OSL chronologies largely support previous age estimates obtained by thermoluminescence dating of burnt flints at Pech IV, electron spin resonance dating of tooth enamel at Pech I, II and IV and radiocarbon dating of bone at Pech I and IV, but provide a more complete picture due to the ubiquitous presence of sand-sized quartz grains used in OSL dating. These complete chronologies for the three sites have allowed us to compare the single-grain ages for similar lithic assemblages among the three sites, to test the correlations among them previously proposed by Bordes in the 1970s, and to construct our own correlative chronological framework for the three sites. This shows that similar lithic assemblages occur at around the same time, and that where a lithic assemblage is unique to one or found at two of the Pech sites, there are no deposits of chronologically equivalent age at the other Pech site(s). We interpret this to mean that, at least for these Pech de l'Aze sites, the Mousterian variants show temporal ordering. Whether or not this conclusion applies to the wider region and beyond, the hypothesis that Mousterian industrial variation is temporally ordered cannot be refuted at this time. PMID- 27260177 TI - Upper third molar internal structural organization and semicircular canal morphology in Plio-Pleistocene South African cercopithecoids. AB - Despite the abundance of cercopithecoids in the fossil record, especially in South Africa, and the recent development of morphometric approaches, uncertainties regarding the taxonomic identification of isolated cranio-dental specimens remain. Because cercopithecoids, nearly always found in stratigraphic association with hominin remains in Plio-Pleistocene deposits, are considered as sensitive ecological and chronological biomarkers, a significant effort should be made to clarify their palaeobiodiversity by assessing additional reliable morphological diagnostic criteria. Here we test the relevance of both molar crown internal structure and bony labyrinth morphology for discrimination of fossil cercopithecoid species. We use microtomographic-based 3D virtual imaging and quantitative analyses to investigate tooth endostructural organization and inner ear shape in 29 craniodental specimens from the South African sites of Kromdraai, Makapansgat, Sterkfontein and Swartkrans and provide the first detailed description of the internal structural condition characterizing this Plio Pleistocene primate assemblage. Our preliminary results show that enamel-dentine junction morphology could be informative for discriminating highly autapomorphic taxa such as Theropithecus, while semicircular canal shape is tentatively proposed as an efficient criterion for diagnosing Dinopithecus ingens. Further research in virtual paleoprimatology may contribute to the identification of unassigned isolated fossil remains and shed new light on the internal craniodental morphology of extinct primate taxa. PMID- 27260178 TI - Adjustment of a Population of South African Children of Mothers Living With/and Without HIV Through Three Years Post-Birth. AB - Mothers living with HIV (MLH) and their children are typically studied to ensure that perinatal HIV transmission is blocked. Yet, HIV impacts MLH and their children lifelong. We examine child outcomes from pregnancy to 3 years post-birth among a peri-urban population of pregnant MLH and mothers without HIV (MWOH). Almost all pregnant women in 12 neighborhoods (98 %; N = 584) in Cape Town, South Africa were recruited and repeatedly assessed within 2 weeks of birth (92 %), at 6 months (88 %), 18 months (84 %), and 3 years post-birth (86 %). There were 186 MLH and 398 MWOH. Controlling for neighborhood and repeated measures, child and maternal outcomes were contrasted over time using longitudinal random effects regression analyses. For measures collected only at 3 years, outcomes were analyzed using multiple regressions. Compared to MWOH, MLH had less income, more informal housing and food insecurity, used alcohol more often during pregnancy, and were more depressed during pregnancy and over time. Only 4.8 % of MLH's children were seropositive; seropositive children were excluded from additional analyses. Children of MLH tended to have significantly lower weights (p < .10) over time (i.e., lower weight-for-age Z-scores) and were also hospitalized significantly more often than children of MWOH (p < .01). Children of MLH and MWOH died at similar rates (8.5 %) and were similar in social and behavioral adjustment, vocabulary, and executive functioning at 3 years post-birth. Despite living in households with fewer resources and having more depressed mothers, only the physical health of children of MLH is compromised, compared to children of MWOH. In township neighborhoods with extreme poverty, social, behavioral, language, and cognitive functioning appear similar over the first three years of life between children of MLH and MWOH. PMID- 27260179 TI - Trajectories of Marijuana Use among HIV-seropositive and HIV-seronegative MSM in the Multicenter AIDS Cohort Study (MACS), 1984-2013. AB - To construct longitudinal trajectories of marijuana use in a sample of men who have sex with men living with or at-risk for HIV infection. We determined factors associated with distinct trajectories of use as well as those that serve to modify the course of the trajectory. Data were from 3658 [1439 HIV-seropositive (HIV+) and 2219 HIV-seronegative (HIV-)] participants of the Multicenter AIDS Cohort Study. Frequency of marijuana use was obtained semiannually over a 29-year period (1984-2013). Group-based trajectory models were used to identify the trajectories and to determine predictors and modifiers of the trajectories over time. Four distinct trajectories of marijuana use were identified: abstainer/infrequent (65 %), decreaser (13 %), increaser (12 %) and chronic high (10 %) use groups. HIV+ status was significantly associated with increased odds of membership in the decreaser, increaser and chronic high use groups. Alcohol, smoking, stimulant and other recreational drug use were associated with increasing marijuana use across all four trajectory groups. Antiretroviral therapy use over time was associated with decreasing marijuana use in the abstainer/infrequent and increaser trajectory groups. Having a detectable HIV viral load was associated with increasing marijuana use in the increaser group only. Future investigations are needed to determine whether long-term patterns of use are associated with adverse consequences especially among HIV+ persons. PMID- 27260180 TI - Economic Resources and HIV Preventive Behaviors Among School-Enrolled Young Women in Rural South Africa (HPTN 068). AB - Individual economic resources may have greater influence on school-enrolled young women's sexual decision-making than household wealth measures. However, few studies have investigated the effects of personal income, employment, and other financial assets on young women's sexual behaviors. Using baseline data from the HIV Prevention Trials Network (HPTN) 068 study, we examined the association of ever having sex and adopting sexually-protective practices with individual-level economic resources among school-enrolled women, aged 13-20 years (n = 2533). Age adjusted results showed that among all women employment was associated with ever having sex (OR 1.56, 95 % CI 1.28-1.90). Among sexually-experienced women, paid work was associated with changes in partner selection practices (OR 2.38, 95 % CI 1.58-3.58) and periodic sexual abstinence to avoid HIV (OR 1.71, 95 % CI 1.07 2.75). Having money to spend on oneself was associated with reducing the number of sexual partners (OR 1.94, 95 % CI 1.08-3.46), discussing HIV testing (OR 2.15, 95 % CI 1.13-4.06), and discussing condom use (OR 1.99, 95 % CI 1.04-3.80). Having a bank account was associated with condom use (OR 1.49, 95 % CI 1.01 2.19). Economic hardship was positively associated with ever having sex, but not with sexually-protective behaviors. Maximizing women's individual economic resources may complement future prevention initiatives. PMID- 27260181 TI - The Information-Motivation-Behavioral Skills Model Revisited: A Network Perspective Structural Equation Model Within a Public Sexually Transmitted Infection Clinic Sample of Hazardous Alcohol Users. AB - The information-motivation-behavioral skills (IMB) model is useful for understanding sexual risk behavior, but has not been tested with hazardously drinking sexually transmitted infection (STI) clinic patients, a subpopulation at greater HIV risk, or with a network-perspective sexual risk behavior outcome. Participants (N = 569) were STI clinic patients who screened positive for hazardous drinking and risky sexual behavior. Sexual risk behavior (SRB) was operationalized as a latent variable with three indicators: (1) number of sexual partners, (2) number of unprotected sex occasions with primary partner, and (3) number of unprotected sex occasions with non-primary partner(s). Preliminary analyses suggested SRB was best operationalized as a latent variable with two indicators, while unprotected sex with primary partners should be considered separately. In structural models with good fit, the IMB model was generally supported. The IMB model functioned differently for non-primary and multiple partners compared to primary partners in STI clinic patients with hazardous alcohol use. PMID- 27260182 TI - The dynamic relationship between health expenditure and economic growth: is the health-led growth hypothesis valid for Turkey? AB - The well-known health-led growth hypothesis claims a positive correlation between health expenditure and economic growth. The aim of this paper is to empirically investigate the health-led growth hypothesis for the Turkish economy. The bound test approach, autoregressive-distributed lag approach (ARDL) and Kalman filter modeling are employed for the 1975-2013 period to examine the co-integration relationship between economic growth and health expenditure. The ARDL model is employed in order to investigate the long-term and short-term static relationship between health expenditure and economic growth. The results show that a 1 % increase in per-capita health expenditure will lead to a 0.434 % increase in per capita gross domestic product. These findings are also supported by the Kalman filter model's results. Our findings show that the health-led growth hypothesis is supported for Turkey. PMID- 27260183 TI - Healthcare inequality issues among immigrant elders after neoliberal welfare reform: empirical findings from the United States. AB - Even with the increasing importance being placed on research into immigrant elders' healthcare use as countries change their policies to reflect their increasing immigrant and aging populations, little research has examined changes in healthcare use disparities between immigrant and native elders in relation to these policy changes. To fill this gap in the literature, this study examined healthcare disparities in relation to the welfare reform that the US implemented in 1996 and then compared significant indicators of immigrants' healthcare use during the pre- and post-reform periods. The difference-in-difference (DD) analyses and post hoc probing of the DD analyses were used in multivariate logistic regression of the National Health Information Survey data that were pooled for the pre- and post-reform periods. The results revealed that while inequalities in healthcare existed before the reform, they significantly increased after the reform. A further test showed that the changes in the inequalities were significant among relatively long-stay immigrants, but not significant among immigrants who entered the US before the reform and thus were exempted from the reform restrictions. During the pre-reform period, insurance, employment, sex, and race/ethnicity were related to healthcare use; however, the enabling factors (i.e., insurance, income, and education) and social structural factors (i.e., marital status, family structure, length of US residency, race/ethnicity, and geographical region) explained the post-reform immigrants' healthcare use, while controlling for healthcare needs factors. These findings suggest that welfare reform may be the driving force of inequalities in healthcare. PMID- 27260184 TI - Cross-country discrepancies on public understanding of stress concepts: evidence for stress-management psychoeducational programs. AB - BACKGROUND: Negative effects of stress have pose one of the major threats to the health and economic well being of individuals independently of age and cultural background. Nevertheless, the term "stress" has been globally used unlinked from scientificevidence-based meaning. The discrepancies between scientific and public stress knowledge are focus of concern and little is know about it. This is relevant since misconceptions about stress may influence the effects of stress management psychoeducational programs and the development of best practices for interventions. The study aimed to analyze stress knowledge among the Canadian and Brazilian general public and to determine the extent to which scientific and popular views of stress differ between those countries. METHODS: We evaluated 1156 healthy participants between 18 and 88 years of age recruited from Canada (n = 502) and Brazil (n = 654). To assess stress knowledge, a questionnaire composed of questions regarding stress concepts ("stress is bad" versus "stress-free life is good") and factors capable of triggering the stress response ("novelty, unpredictability, low sense of control and social evaluative threat versus "time pressure,work overload, conflict, unbalance and children") was used. RESULTS: Both Canadian and Brazilian participants showed misconceptions about stress and the factors capable of triggering a stress response. However, the rate of misconceptions was higher in Brazil than in Canada (p < 0.05). CONCLUSION: These findings suggest a lack of public understanding of stress science and its variance according to a country's society. Psychoeducational programs and vulnerability of stress-related disorder are discussed. PMID- 27260185 TI - Is phytoestrogen intake associated with decreased risk of prostate cancer? A systematic review of epidemiological studies based on 17,546 cases. AB - This study uses current epidemiological data to evaluate whether phytoestrogen intake is associated with a reduced risk of prostate cancer. We performed a random-effect meta-analysis of published data retrieved from PubMed, Web of Science, ProQuest, and CNKI, which was supplemented by a manual search of relevant references. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Subgroup analysis and meta-regression were performed to explore the source of heterogeneity. Sensitivity analysis was evaluated to assess the stability of the results. Egger's test and funnel plots were used to detect the existence of publication bias. We retrieved 507 papers, and 29 studies were ultimately confirmed as eligible. The meta-analysis showed that phytoestrogen intake was significantly associated with a reduced risk of prostate cancer, with an odds ratio (OR) of 0.77 (95% CI 0.66-0.88; I(2) = 77.6%). The food/nutritional sources that were significantly associated with a reduced risk of prostate cancer included soy and soy products, tofu, legumes, daidzein, and genistein. Subgroup analysis indicated that the associations were significant among Asians and Caucasians, but not among Africans. Meta-regression revealed that the pooled OR increased with the number of cases in the studies. The results might be affected by publication bias based on the Eggers' test (p = 0.011) and the asymmetry of the funnel plot. Phytoestrogen intake may reduce the risk of prostate cancer in Asians and Caucasians. Regular intake of food that is rich in phytoestrogens, such as soy/soy products or legumes, should be recommended. PMID- 27260186 TI - Effects of diazinon on the lymphocytic cholinergic system of Nile tilapia fish (Oreochromis niloticus). AB - Fish rearing under intensive farming conditions can be easily disturbed by pesticides, substances that have immunotoxic properties and may predispose to infections. Organophosphorus pesticides (OPs) are widely used in agricultural activities; however, the mechanism of immunotoxicity of these substances is unclear. The aim of this study was to evaluate the effect of diazinon pesticides (OPs) on the cholinergic system of immune cells as a possible target of OP immunotoxicity. We evaluated ACh levels and cholinergic (nicotinic and muscarinic) receptor concentration. Additionally, AChE activity was evaluated in mononuclear cells of Nile tilapia (Oreochromis niloticus), a freshwater fish mostly cultivated in tropical regions around the world. The obtained results indicate that acute exposure to diazinon induces an increase in ACh concentration and a decrease in nAChR and mAChR concentrations and AChE activity in fish immune cells, This suggests that the non-neuronal lymphocytic cholinergic system may be the main target in the mechanism of OP immunotoxicity. This study contributes to the understanding of the mechanisms of immunotoxicity of pollutants and may help to take actions for animal health improvement. PMID- 27260187 TI - Nutrient limitation drives response of Calamagrostis epigejos to arbuscular mycorrhiza in primary succession. AB - Little is known about the functioning of arbuscular mycorrhizal (AM) symbiosis over the course of primary succession, where soil, host plants, and AM fungal communities all undergo significant changes. Over the course of succession at the studied post-mining site, plant cover changes from an herbaceous community to the closed canopy of a deciduous forest. Calamagrostis epigejos (Poaceae) is a common denominator at all stages, and it dominates among AM host species. Its growth response to AM fungi was studied at four distinctive stages of natural succession: 12, 20, 30, and 50 years of age, each represented by three spatially separated sites. Soils obtained from all 12 studied sites were gamma-sterilized and used in a greenhouse experiment in which C. epigejos plants were (1) inoculated with a respective community of native AM fungi, (2) inoculated with reference AM fungal isolates from laboratory collection, or (3) cultivated without AM fungi. AM fungi strongly boosted plant growth during the first two stages but not during the latter two, where the effect was neutral or even negative. While plant phosphorus (P) uptake was generally increased by AM fungi, no contribution of mycorrhizae to nitrogen (N) uptake was recorded. Based on N:P in plant biomass, we related the turn from a positive to a neutral/negative effect of AM fungi on plant growth, observed along the chronosequence, to a shift in relative P and N availability. No functional differences were found between native and reference inocula, yet root colonization by the native AM fungi decreased relative to the reference inoculum in the later succession stages, thereby indicating shifts in the composition of AM fungal communities reflected in different functional characteristics of their members. PMID- 27260188 TI - Association of three single nucleotide polymorphisms at the SIX1-SIX6 locus with primary open angle glaucoma in the Chinese population. AB - This study investigated the genetic association of three single nucleotide polymorphisms (SNPs; rs10483727, rs33912345, and rs146737847) at the SIX1-SIX6 locus with primary open angle glaucoma (POAG) in the Chinese population. A total of 866 subjects with POAG (685 high-tension glaucoma (HTG) and 181 normal-tension glaucoma (NTG)) and 266 control individuals were included. Significant genetic association was identified for rs10483727 in HTG (P=0.02; odds ratio (OR)=1.31), NTG (P=7.41*10(-6); OR=2.71), and POAG (i.e., HTG and NTG combined; P=0.001; OR=1.44). rs33912345 was also significantly associated with HTG (P=0.008; OR=1.36), NTG(P=2.72*10(-6); OR=2.27), and POAG (P=3.84*10(-4); OR=1.49). The rare SIX6 mutation, rs146737847, was not found in the subjects enrolled in this study. Stratification by patient age identified that both rs10483727 and rs33912345 were significantly associated with NTG in patients aged above 40 years (P=2.08*10(-5); OR=2.28), whereas in patients aged between 20-40 years, rs33912345 was significantly associated with NTG (P=0.017; OR=2.06). In HTG, the genetic associations for both rs10483727 and rs33912345 were significant in patients aged between 20-40 years (P=0.006; OR=1.56) but not in those aged above 40 years (P=0.118, OR=1.21 and P=0.042, OR=1.29, respectively). This study replicated the association of POAG with two SNPs at the SIX1-SIX6 locus and demonstrated that SNPs, rs10483727 and rs33912345, are significantly associated with POAG, especially with NTG in patients aged above 40 years. PMID- 27260189 TI - Prognostic and predictive impacts of tumor-infiltrating lymphocytes differ between Triple-negative and HER2-positive breast cancers treated with standard systemic therapies. AB - Tumor-infiltrating lymphocytes (TILs) have potential value for stratifying the treatment of breast cancer (BC), though their precise use remains unclear. We aimed to investigate the utility of TILs using an alternative approach in different settings. We reviewed patients with triple-negative (TN) or human epithelial growth factor receptor 2 (HER2)-positive invasive ductal carcinomas from a single institutional cohort and classified archived hematoxylin-eosin stained samples in terms of TIL score as low (<10 %), intermediate, and high (>50 %). The prognostic and predictive values of TILs were analyzed retrospectively in both adjuvant and neo-adjuvant settings. In the adjuvant setting, the presence of TILs at primary surgery was a significant favorable prognostic factor among 154 TNBCs [relapse-free survival (RFS): p = 0.015], but not among 183 HER2+ BCs (RFS: p = 0.097). The TNBC low-TIL group tended to relapse earlier. In the neo-adjuvant setting, detection of TILs on biopsy before primary systemic therapy was associated with the ratio of patients achieving pathological complete response among 48 TNBCs (p = 0.024), but not among 58 HER2+ BCs (p = 0.30). The presence of TILs in surgical specimens after systemic therapy had prognostic value in HER2+ BC (RFS: p = 0.007). The impact of TILs differs between patients with TN and HER2+ BC treated with standard therapies. Our three-grade scale for TILs may contribute to our understanding of the importance of the tumor microenvironment in routine practice. TILs after primary systemic therapy may be useful for the further stratification of treatment of HER2+ BC. PMID- 27260190 TI - Chronic Pruritus and Connective Tissue Disorders: Review, Gaps, and Future Directions. AB - Chronic itch is a common skin manifestation in many connective tissue diseases. However, the cause of chronic itch in these diseases is still not fully understood. The complex, and in some cases incomplete understanding of, pathogenesis in each condition makes it difficult to target specific mediators of chronic itch. It is important to better understand the pathophysiology of chronic itch in these conditions, as this information might provide a fuller understanding of the pathogenesis of the diseases in general and lead to the development of more specific treatments for connective tissue diseases in patients with chronic itch. We present a review of the literature on what is known about the prevalence, possible pathophysiology, and effect on quality of life of chronic itch in patients with scleroderma, Sjogren's syndrome, dermatomyositis, systemic lupus erythematosus, cutaneous lupus erythematosus, and mixed connective tissue disease. PMID- 27260192 TI - An immunological perspective on rheumatic heart disease pathogenesis: more questions than answers. AB - Acute rheumatic fever (ARF) and the related rheumatic heart disease (RHD) are autoimmune diseases thought to be triggered by group A streptococcal (GAS) pharyngitis. RHD is a leading cause of mortality in the developing world. The strong epidemiological association between GAS throat infection and ARF is highly suggestive of causation, but does not exclude other infections as contributory. There is good evidence of both humoral and cellular autoreactivity and GAS/self cross-reactivity in established RHD. RHD pathogenesis could feasibly be triggered and driven by humoral and/or cellular molecular cross-reactivity between GAS and host cardiac tissues (molecular mimicry). However, good evidence of humoral pathogenicity is lacking and the specific triggering event for RHD remains unknown. It is likely that the critical immunological events leading to ARF/RHD occur at the point of contact between GAS and the immune system in the throat, strongly implicating the mucosal immune system in RHD pathogenesis. Additionally, there is circumstantial evidence that continued live GAS may play a role in ARF/RHD pathogenesis. We suggest that future avenues for study should include the exclusion of GAS components directly contributing to RHD pathogenesis; large genome-wide association studies of patients with RHD looking for candidate genes involved in RHD pathogenesis; genome-wide association studies of GAS from patients with ARF taken at diagnosis to look for characteristics of rheumatogenic strains; and performing case/control studies of GAS pharyngitis/ARF/patients with RHD, and controls to identify microbiological, immunological and environmental differences to elucidate RHD pathogenesis. PMID- 27260191 TI - Comprehensive characterisation of hypertensive heart disease left ventricular phenotypes. AB - OBJECTIVE: Myocardial intracellular/extracellular structure and aortic function were assessed among hypertensive left ventricular (LV) phenotypes using cardiovascular magnetic resonance (CMR). METHODS: An observational study from consecutive tertiary hypertension clinic patients referred for CMR (1.5 T) was performed. Four LV phenotypes were defined: (1) normal with normal indexed LV mass (LVM) and LVM to volume ratio (M/V), (2) concentric remodelling with normal LVM but elevated M/V, (3) concentric LV hypertrophy (LVH) with elevated LVM but normal indexed end-diastolic volume (EDV) or (4) eccentric LVH with elevated LVM and EDV. Extracellular volume fraction was measured using T1-mapping. Circumferential strain was calculated by voxel-tracking. Aortic distensibility was derived from high-resolution aortic cines and contemporaneous blood pressure measurements. RESULTS: 88 hypertensive patients (49+/-14 years, 57% men, systolic blood pressure (SBP): 167+/-30 mm Hg, diastolic blood pressure (DBP): 96+/-14 mm Hg) were compared with 29 age-matched/sex-matched controls (47+/-14 years, 59% men, SBP: 128+/-12 mm Hg, DBP: 79+/-10 mm Hg). LVH resulted from increased myocardial cell volume (eccentric LVH: 78+/-19 mL/m(2) vs concentric LVH: 73+/-15 mL/m(2) vs concentric remodelling: 55+/-9 mL/m(2), p<0.05, respectively) and interstitial fibrosis (eccentric LVH: 33+/-10 mL/m(2) vs concentric LVH: 30+/-10 mL/m(2) vs concentricremodelling: 19+/-2 mL/m(2), p<0.05, respectively). LVH had worst circumferential impairment (eccentric LVH: -12.8+/-4.6% vs concentric LVH: 15.5+/-3.1% vs concentric remodelling: -17.1+/-3.2%, p<0.05, respectively). Concentric remodelling was associated with reduced aortic distensibility, but not with large intracellular/interstitial expansion or myocardial dysfunction versus controls. CONCLUSIONS: Myocardial interstitial fibrosis varies across hypertensive LV phenotypes with functional consequences. Eccentric LVH has the most fibrosis and systolic impairment. Concentric remodelling is only associated with abnormal aortic function. Understanding these differences may help tailor future antihypertensive treatments. PMID- 27260193 TI - The impact of electronic records on patient safety: a qualitative study. AB - BACKGROUND: Our aim was to explore NHS staff perceptions and experiences of the impact on patient safety of introducing a maternity system. METHODS: Qualitative semi-structured interviews were conducted with 19 members of NHS staff who represented a variety of staff groups (doctors, midwives, health care assistants), staff grades (consultant and midwife grades) and wards within a maternity unit. Participants represented a single maternity unit at a NHS teaching hospital in the North of England. Interviews were conducted during the first 12 months of the system being implemented and were analysed thematically. RESULTS: Participants perceived there to be an elevated risk to patient safety during the system's implementation. The perceived risks were attributed to a range of social and technical factors. For example, poor system design and human error which resulted in an increased potential for missing information and inputting error. CONCLUSIONS: The first 12 months of introducing the maternity system was perceived to and in some cases had already caused actual risk to patient safety. Trusts throughout the NHS are facing increasing pressure to become paperless and should be aware of the potential adverse impacts on patient safety that can occur when introducing electronic systems. Given the potential for increased risk identified, recommendations for further research and for NHS trusts introducing electronic systems are proposed. PMID- 27260194 TI - Microorganism-regulated mechanisms of temperature effects on the performance of anaerobic digestion. AB - BACKGROUND: Temperature is an important factor determining the performance and stability of the anaerobic digestion process. However, the microorganism regulated mechanisms of temperature effects on the performance of anaerobic digestion systems remain further elusive. To address this issue, we investigated the changes in composition, diversity and activities of microbial communities under temperature gradient from 25 to 55 degrees C using 16S rRNA gene amplicon sequencing approach based on genomic DNA (refer to as "16S rDNA") and total RNA (refer to as "16S rRNA"). RESULTS: Microbial community structure and activities changed dramatically along the temperature gradient, which corresponded to the variations in digestion performance (e.g., daily CH4 production, total biogas production and volatile fatty acids concentration). The ratios of 16S rRNA to 16S rDNA of microbial taxa, as an indicator of the potentially relative activities in situ, and whole activities of microbial community assessed by the similarity between microbial community based on 16S rDNA and rRNA, varied strongly along the temperature gradient, reflecting different metabolic activities. The daily CH4 production increased with temperature from 25 to 50 degrees C and declined at 55 degrees C. Among all the examined microbial properties, the whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities showed highest correlations to the performance. CONCLUSIONS: The whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities were sensitive indicators for the performance of anaerobic digestion systems under temperature gradient, while beta-diversity could predict functional differences. Microorganism-regulated mechanisms of temperature effects on anaerobic digestion performance were likely realized through increasing alpha-diversity of both microbial communities and potentially relative activities to supply more functional pathways and activities for metabolic network, and increasing the whole activities of microbial community, especially methanogenesis, to improve the strength and efficiency in anaerobic digestion process. PMID- 27260195 TI - [Not Available]. PMID- 27260196 TI - Co-morbidities, complications and causes of death among people with femoral neck fracture - a three-year follow-up study. AB - BACKGROUND: The poor outcome after a hip fracture is not fully understood. The aim of the study was to describe the prevalence of co-morbidities, complications and causes of death and to investigate factors that are able to predict mortality in old people with femoral neck fracture. METHODS: Data was obtained from a randomized, controlled trial with a 3-year follow-up at Umea University Hospital, Sweden, which included 199 consecutive patients with femoral neck fracture, aged >=70 years. The participants were assessed during hospitalization and in their homes 4, 12 and 36 months after surgery. Medical records and death certificates were analysed. RESULTS: Multivariate analysis revealed that cancer, dependence in P-ADL (Personal Activities of Daily Living), cardiovascular disease, dementia at baseline or pulmonary emboli or cardiac failure during hospitalization were all independent predictors of 3-year mortality. Seventy-nine out of 199 participants (40 %) died within 3 years. Cardiovascular events (24 %), dementia (23 %), hip fracture (19 %) and cancer (13 %) were the most common primary causes of death. In total, 136 participants suffered at least one urinary tract infection; 114 suffered 542 falls and 37 sustained 56 new fractures, including 13 hip fractures, during follow-up. CONCLUSION: Old people with femoral neck fracture have multiple co-morbidities and suffer numerous complications. Thus randomized intervention studies should focus on prevention of complications that might be avoidable such as infections, heart diseases, falls and fractures. PMID- 27260197 TI - Imaging Invasion: Micro-CT imaging of adamantinomatous craniopharyngioma highlights cell type specific spatial relationships of tissue invasion. AB - Tissue invasion and infiltration by brain tumours poses a clinical challenge, with destruction of structures leading to morbidity. We assessed whether micro-CT could be used to map tumour invasion in adamantinomatous craniopharyngioma (ACP), and whether it could delineate ACPs and their intrinsic components from surrounding tissue.Three anonymised archival frozen ACP samples were fixed, iodinated and imaged using a micro-CT scanner prior to the use of standard histological processing and immunohistochemical techniques.We demonstrate that micro-CT imaging can non-destructively give detailed 3D structural information of tumours in volumes with isotropic voxel sizes of 4-6 microns, which can be correlated with traditional histology and immunohistochemistry.Such information complements classical histology by facilitating virtual slicing of the tissue in any plane and providing unique detail of the three dimensional relationships of tissue compartments. PMID- 27260198 TI - Analysis of histone post translational modifications in primary monocyte derived macrophages using reverse phase*reverse phase chromatography in conjunction with porous graphitic carbon stationary phase. AB - A two dimensional-liquid chromatography (2D-LC) based approach was developed for the identification and quantification of histone post translational modifications in conjunction with mass spectrometry analysis. Using a bottom-up strategy, offline 2D-LC was developed using reverse phase chromatography. A porous graphitic carbon stationary phase in the first dimension and a C18 stationary phase in the second dimension interfaced with mass spectrometry was used to analyse global levels of histone post translational modifications in human primary monocyte-derived macrophages. The results demonstrated that 84 different histone peptide proteoforms, with modifications at 18 different sites including combinatorial marks were identified, representing an increase in the identification of histone peptides by 65% and 51% compared to two different 1D-LC approaches on the same mass spectrometer. The use of the porous graphitic stationary phase in the first dimension resulted in efficient separation of histone peptides across the gradient, with good resolution and is orthogonal to the online C18 reverse phase chromatography. Overall, more histone peptides were identified using the 2D-LC approach compared to conventional 1D-LC approaches. In addition, a bioinformatic pipeline was developed in-house to enable the high throughput efficient and accurate quantification of fractionated histone peptides. The automation of a section of the downstream analysis pipeline increased the throughput of the 2D-LC-MS/MS approach for the quantification of histone post translational modifications. PMID- 27260199 TI - Center-cut separation of intermediately adsorbing target component by 8-zone simulated moving bed chromatography with internal recycle. AB - An 8-zone simulated moving bed chromatography with internal recycle (8ZSMB-IR) has been designed for center-cut separation, that is, for isolating an intermediately adsorbed component out of a multicomponent mixture. The system consists of two integrated subunits and operates in a fully continuous manner. In the first subunit the feed mixture is split into two fractions containing either a single component or a binary mixture. The binary mixture is recycled through the internal raffinate or extract port into the second subunit, where the target product is isolated. Additionally, the solvent is also recycled internally. For a case study, the separation of a ternary mixture of cycloketones as a model system under weakly non-linear isotherm conditions has been investigated. A few novel configurations of the 8ZSMB-IR unit including the arrangement of the internal recycle of extract, raffinate and solvent streams between two subunits have been examined with respect to various performance indicators for the process realization. The unit performed best with the developed configuration when the internal raffinate stream was recycled and the solvent recycling loop was closed between the last and the first zone of the first subunit. That configuration has further been analyzed experimentally and numerically. On the basis of the results a strategy for determining reliable operating conditions for the 8ZSMB-IR process has been developed. The procedure exploited a model of the process dynamics, which was implemented to refine the isotherm coefficients and to quantify the mixing effect of the liquid stream inside the recycling loops. The upgraded model with the adjusted parameters has been validated based on experimental data and successfully applied for optimizing the operating conditions of the separation. PMID- 27260200 TI - GPs told to end "chemical restraint" of people with learning disabilities. PMID- 27260201 TI - Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment. AB - Tricyclic antidepressants (TCAs) are found to have an analgesic action for relieving cutaneous pain associated with neuropathies. The aim of this study was to assess cutaneous absorption and analgesia of topically applied TCAs. Percutaneous delivery was investigated using nude mouse and pig skin models at both infinite and saturated doses. We evaluated the cutaneous analgesia in nude mice using the pinprick scores. Among five antidepressants tested in the in vitro experiment, mesoridazine, promazine and doxepin showed a superior total absorption percentage. The drug with the lowest total absorption percentage was found to be fluphenazine (<7%) either at an infinite dose or at saturated solubility. The follicular pathway was important for mesoridazine and promazine delivery. Mesoridazine showed stronger skin analgesia than the other TCAs although the in vivo skin absorption of mesoridazine (0.34nmol/mg) was less than that of promazine (0.80nmol/mg) and doxepin (0.74nmol/mg). Mesoridazine had a prolonged duration of pain relief (165min) compared to promazine (83min) and doxepin (17min). The skin irritation test demonstrated an evident barrier function deterioration and cutaneous erythema by promazine and doxepin treatment, whereas mesoridazine caused no obvious adverse effect by topical application for up to 7days. PMID- 27260202 TI - Properties and mechanisms of drug release from matrix tablets containing poly(ethylene oxide) and poly(acrylic acid) as release retardants. AB - The interactions between poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) in aqueous medium at pH 6.8 were investigated in the current study. We have also studied the effect of interpolymer interactions and various formulation variables, including the molecular weight of PEO, the ratio between PEO and PAA, the crystallinity of PEO, and the presence of an acidifying agent, on the release of theophylline from matrix tablets containing both PEO and PAA as release retardants. At pH 6.8, the synergy in solution viscosity between PEO and PAA as the result of ion-dipole interaction was observed in this study. The release of theophylline from the matrix tablets containing physical mixtures of PEO and PAA was found to be a function of dissolution medium pH because of the pH-dependent interactions between these two polymers. Because of the formation of water insoluble interpolymer complex between PEO and PAA in aqueous medium at pH below 4.0, the release of theophylline was independent of PEO molecular weight and was controlled by Fickian diffusion mechanism in 0.01N hydrochloric acid solution. In comparison, the drug release was a function of PEO molecular weight and followed the anomalous transport mechanism in phosphate buffer pH 6.8. The presence of PAA exerted opposite effects on the release of theophylline in phosphate buffer pH 6.8. In one aspect, theophylline release was accelerated because the erosion of PAA was much faster than that of PEO at pH6.8. On the opposite aspect, theophylline release was slowed down because of the formation of insoluble complex inside the gel layer as the result of the acidic microenvironment induced by PAA, and the increase in the viscosity of the gel layer as the result of the synergy between PEO and PAA. These two opposite effects offset each other. As a result, the release of theophylline remained statistically the same even when 75% PEO in the formulation was replaced with PAA. In phosphate buffer pH 6.8, the release of theophylline was independent of the crystalline form of PEO. The release profile remained identical whether PEO was present as a semicrystalline powder blend with PAA or an amorphous complex with PAA in the matrix tablets. It has also been observed that the presence of citric acid as an acidifying agent had negligible effect on the drug release rate. PMID- 27260205 TI - Update on the mechanisms of homing of adipose tissue-derived stem cells. AB - Adipose tissue-derived stem cells (ADSCs), which resemble bone marrow mesenchymal stromal cells (BMSCs), have shown great advantages and promise in the field of regenerative medicine. They can be readily harvested in large numbers with low donor-site morbidity. To date, a great number of preclinical and clinical studies have shown ADSCs' safety and efficacy in regenerative medicine. However, a better understanding of the mechanisms of homing of ADSCs is needed to advance the clinical utility of this therapy. In this review, the reports of the homing of ADSCs were searched using Pubmed and Google Scholar to update our knowledge. ADSCs were proved to interact with endothelial cells by expressing the similar integrins with BMSCs. In addition, ADSCs do not possess the dominant ligand for P selectin, just like BMSCs. Stromal derived factor-1 (SDF-1)/CXCR4 and CXC ligand 5 (CXCL5)/CXCR2 interactions are the two main axes governing ADSCs extravasation from bone marrow vessels. Some more signaling pathways involved in migration of ADSCs have been investigated, including LPA/LPA1 signaling pathway, MAPK/Erk1/2 signaling pathway, RhoA/Rock signaling pathway and PDGF-BB/PDGFR-beta signaling pathway. Status quo of a lack of intensive studies on the details of homing of ADSCs should be improved in the near future before clinical application. PMID- 27260204 TI - Genetic dynamics in the sand fly (Diptera: Psychodidae) nuclear and mitochondrial genotypes: evidence for vector adaptation at the border of Iran with Iraq. AB - BACKGROUND: Our investigation uses nucleotide variations of the genera Phlebotomus and Sergentomyia using the EF-1alpha and Cyt b genotype regions to describe the sand fly fauna and genetic aspects collected at war-torn sites of the Khuzestan boundary between Iraq and Iran. METHODS: All sand fly species were characterized using molecular genetics. The field work was conducted in six districts including 24 locations in remote areas for three years at the peak of sand fly activity during cutaneous leishmaniasis (CL) transmission seasons. The distribution of CL vectors was determined based on the climatic regionalization using the kriging method in ArcGIS model. DNA of sand fly pools were screened via polymerase chain reaction (PCR) using neutrality (Tajima's D) and neutral allele frequency (Fu's F s) tests to measure the effect of randomly evolving DNA sequence on the genetic diversity of sand fly populations in response to habitat fragmentation and landscape modification. RESULTS: Among the 1213 specimens, ten species were identified based on morphology. The non-native species Phlebotomus sergenti was unequivocally found for the first time in the studied regions. Nucleotide substitutions of sand fly sequences varied most in the most disrupted districts (Dashte-Azadegan and Abadan; disparity index test: P < 0.05). The haplotypes of Cyt b from the subgenus Sergentomyia and P. papatasi revealed more heterogeneity (Tajima's D > +2) than P. alexandri (D > +1), which suggests widespread heteroplasmic mitochondrial DNA mutations in the same mtDNA gene among different sand fly species. Subgenus Sintonius exhibited greater fitness (D = 0) and (neutrality test; P > 0.05) no evidence of selection. The sequence of the nuclear gene EF-1alpha indicated similar nucleotide differences, as observed for the Cyt b gene, in all sand fly species, but lower levels of polymorphisms (D > +1) were observed compared with the mitochondrial Cyt b gene (D > +2) in the subgenus Sergentomyia. CONCLUSION: Our findings describe random nucleotide diversity in the Phlebotomus and Sergentomyia population gene pools due to recent anthropogenic influence. A phylogenetic analysis showed that the closely related species are positioned in monophyletic clades, except for the subgenus Sergentomyia and P. sergenti, and highlights the importance of haplotype variations for the development of adaptability. PMID- 27260203 TI - Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates. AB - The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling. PMID- 27260206 TI - DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine. AB - Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1beta and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-alpha expression, increased expression of transforming growth factor (TGF)-beta1, increased percentages of BM MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)gamma, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC. PMID- 27260207 TI - Cryopreservation of human mesenchymal stromal cells expressing TRAIL for human anti-cancer therapy. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are being extensively researched for cell therapy and tissue engineering. We have engineered MSCs to express the pro-apoptotic protein tumor necrosis factor-related apoptosis inducing ligand (TRAIL) and are currently preparing this genetically modified cell therapy for a phase 1/2a clinical trial in patients with metastatic lung cancer. To do this, we need to prepare a cryopreserved allogeneic MSCTRAIL cell bank for further expansion before patient delivery. The effects of cryopreservation on a genetically modified cell therapy product have not been clearly determined. METHODS: We tested different concentrations of dimethyl sulfoxide (DMSO) added to the human serum albumin ZENALB 4.5 and measured post thaw cell viability, proliferation ability and differentiation characteristics. In addition, we examined the homing ability, TRAIL expression and cancer cell killing capacities of cryopreserved genetically modified MSCs compared with fresh, continually cultured cells. RESULTS: We demonstrated that the post-thaw viability of MSCs in 5% DMSO (v/v) with 95% ZENALB 4.5 (v/v) is 85.7 +/- 0.4%, which is comparable to that in conventional freezing media. We show that cryopreservation does not affect the long-term expression of TRAIL and that cryopreserved TRAIL-expressing MSCs exhibit similar levels of homing and, importantly, retain their potency in triggering cancer cell death. CONCLUSIONS: This study shows that cryopreservation is unlikely to affect the therapeutic properties of MSCTRAIL and supports the generation of a cryopreserved master cell bank. PMID- 27260208 TI - Bone marrow-derived mesenchymal stromal cell therapy in a rat model of cavernous nerve injury: Preclinical study for approval. AB - BACKGROUND AIMS: Although clinical studies using stem cells to treat erectile dysfunction have been performed or are ongoing, there is little consensus on the optimal protocol. We aimed to develop a protocol optimizing human bone marrow derived mesenchymal stromal cell (hBMSC) therapy in a rat model of cavernous nerve injury. METHODS: We performed, in order, a dose-finding study, a toxicokinetic study of hBMSCs, and a study to determine the timing and number of cell injections. RESULTS: From the dose-finding study, 1 * 10(6) cells were selected as the dose per hBMSC injection. From the toxicokinetic study, 14 days was selected as the interval between repeat treatments. In the final study, the ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (23.4% vs. 55.1%, P <0.001). An immediate single injection of hBMSCs significantly improved erectile function compared with the control group (39.8%, P = 0.035), whereas a delayed single injection showed improvement with a marginal trend (38.1%, P = 0.079). All histomorphometric changes were significantly more improved in the immediate or delayed single injection groups than in the control group. Repeat treatments did not provide any benefit for the recovery of erectile function and histomorphometric changes. CONCLUSIONS: Intracavernous injection of 1 * 10(6) hBMSCs results in a recovery of penile erection and histomorphometric changes in a rat model of cavernous nerve injury, even when treatment was delayed until 4 weeks after cavernous nerve injury. PMID- 27260209 TI - Bioengineering and serum free expansion of blood-derived gammadelta T cells. AB - BACKGROUND AIMS: Cellular immunotherapy relies on several highly variable patient specific parameters, such as (i) cell number before and after expansion, (ii) targeting of cells to tumors, (iii) cell survival and function after infusion, and (iv) on- and off-target adverse events. Cellular approaches such as the specific expansion of gammadelta T cells as opposed to alphabeta T cells are being pursued. gammadelta T cells are reasonable candidates for immunotherapy because they (i) possess intrinsic anti-tumorigenicity, (ii) require no priming, (iii) direct tumor killing via recognition of stress-responsive ligands, and (iv), as we now show, can be expanded to clinical cell doses in current Good Manufacturing Practice serum-free media (SFM). METHODS: gammadelta T-cell expansion was evaluated in several SFMs. Additionally, the expanded gammadelta T cells were evaluated for their transduction efficiency using lentiviral vectors (LV). RESULTS: Of the SFM cultures, robust expansion was only observed in OpTmizer supplemented with high-dose interleukin-2. gammadelta T-cell percentages and numbers were sufficient for clinical use. Using cells from several donors, transduction efficiencies ranged from 13 to 33%, which is similar to transduction levels observed using alphabeta T cells with similar multiplicity of infection. DISCUSSION: An optimized method of gammadeltaT-cell expansion and transduction was developed that can be tested in early-phase clinical trials. With appropriate elimination of the alphabetaT cell-component, the absence of MHC-restriction affords the opportunity for use in the allogeneic setting with limited risk of graft versus host disease. Finally, the use of SFM provides clinically safer, widely applicable and potentially more efficacious cellular immunotherapy. PMID- 27260210 TI - Removal process of prion and parvovirus from human platelet lysates used as clinical-grade supplement for ex vivo cell expansion. AB - BACKGROUND AIMS: Pooled human platelet lysate (HPL) is becoming the new gold standard as supplement for ex vivo cell culture for clinical protocols. However, the risk of pathogen contamination of HPL increases with the platelet pool size. We hypothesized that hollow fiber anion exchange membrane chromatography using QyuSpeed D (QSD) could remove resistant and untested bloodborne pathogens, such as parvoviruses and prions, from HPL-supplemented growth media without substantially affecting their capacity to support ex vivo cell expansion. METHODS: Frozen or thawed platelet concentrates were serum-converted and centrifuged for obtaining HPL that was added to various growth media (ca. 100 mL), filtered through a 0.6-mL QSD membrane and characterized for proteins, growth factors and chemical composition. Capacity to expand Chinese hamster ovary, periodontal ligament, gingival fibroblast cells and Wharton's jelly mesenchymal stromal cells was studied. Removal of porcine parvovirus (PPV) and of the 263K prion strain of hamster-adapted scrapie was studied by spiking experiments following international guidelines. RESULTS: QSD had minimal impact on HPL-supplemented medium composition in proteins, growth factors and chemical content, nor capacity to expand and differentiate cells. In addition, QSD could remove >=5.58 log10 [TCID50/mL] and >=3.72 log10 of PPV and the 263K prion, respectively. CONCLUSIONS: QSD hollow fiber chromatography can be used to improve the virus and prion safety of HPL-supplemented media to safely expand cells for clinical protocols. These data bring new perspectives for increasingly safer use of pooled HPL in cell therapy and regenerative medicine applications. PMID- 27260211 TI - Ferulic acid pretreatment could improve prognosis of autologous mesenchymal stromal cell transplantation for diabetic neuropathy. PMID- 27260212 TI - The Evolution of Physical Activity and Recommendations for Patients with Coronary Heart Disease. PMID- 27260213 TI - Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection. AB - The nucleoprotein (NP) possesses regions that are highly conserved among influenza A viruses, and has therefore been one of the target viral proteins for development of a universal influenza vaccine. It has been expected that human or humanized antibodies will be made available for the prophylaxis, pre-emptive and acute treatment of viral infection. However, it is still unclear whether anti-NP human antibody can confer protection against influenza virus infection. In this study, we generated transgenic mice expressing anti-NP human mAbs derived from lymphocytes of a patient infected with H5N1 highly pathogenic avian influenza (HPAI) virus, and experimental infections were conducted to examine antiviral effects of the anti-NP antibodies against H5N1 HPAI viral infections with a high fatality rate in mammals. Transgenic mouse lines expressing the anti-NP human mAbs at more than 1 mg ml-1 showed marked resistance to H5N1 virus infections. In addition, resistance to infection with an H1N1 subtype that shows strong pathogenicity to mice was also confirmed. Although the anti-NP mAbs expressed in the transgenic mice did not neutralize the virus, the mAbs could bind to NP located on the surface of infected cells. These results suggested a possibility that the non-neutralizing anti-NP human mAbs could induce indirect antiviral effects, such as antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity. Taken together, these results demonstrated that anti-NP human mAbs play an important role in heterosubtypic protection against lethal influenza virus infections in vivo. PMID- 27260214 TI - Are all repeats created equal? Understanding DNA repeats at an individual level. AB - Repetitive DNA sequences, comprising up to 50 % of the genome in all eukaryotes, play important roles in a wide range of cellular functions, such as transcriptional regulation, genome stability, and cellular differentiation. However, due to technical difficulties in differentiating their sequences, DNA repeats remain one of the most mysterious parts of eukaryotic genomes. Key questions, such as how repetitive entities behave at individual level and how the internal architecture of these repeats is organized, are still poorly understood. Recent advances from our group reveal unexpected position-dependent variation within tandem DNA repeats in fission yeast. Despite sharing identical DNA sequences, the peri-centromeric repeats are organized into diverse epigenetic states and chromatin structures. We demonstrate that this position-dependent variation requires key heterochromatin factors and condensin. Our works further suggest that the peri-centromeric repeats are organized into distinct higher order structures that ensure a proper positioning of CENP-A, the centromere specific histone H3 variant, to centromeres. These most recent developments offer insights into the mechanisms underlying the position effect within tandem DNA arrays, and have broad implications in the field of epigenetics and chromatin biology. PMID- 27260215 TI - Advanced assessment of the physicochemical characteristics of Remicade(r) and Inflectra(r) by sensitive LC/MS techniques. AB - In this study, we demonstrate the utility of ultra-performance liquid chromatography coupled to mass spectrometry (MS) and ion-mobility spectrometry (IMS) to characterize and compare reference and biosimilar monoclonal antibodies (mAbs) at an advanced level. Specifically, we focus on infliximab and compared the glycan profiles, higher order structures, and their host cell proteins (HCPs) of the reference and biosimilar products, which have the brand names Remicade(r) and Inflectra(r), respectively. Overall, the biosimilar attributes mirrored those of the reference product to a very high degree. The glycan profiling analysis demonstrated a high degree of similarity, especially among the higher abundance glycans. Some differences were observed for the lower abundance glycans. Glycans terminated with N-glycolylneuraminic acid were generally observed to be at higher normalized abundance levels on the biosimilar mAb, while those possessing alpha linked galactose pairs were more often expressed at higher levels on the reference molecule. Hydrogen deuterium exchange (HDX) analyses further confirmed the higher-order similarity of the 2 molecules. These results demonstrated only very slight differences between the 2 products, which, interestingly, seemed to be in the area where the N-linked glycans reside. The HCP analysis by a 2D-UPLC IMS-MS approach revealed that the same 2 HCPs were present in both mAb samples. Our ability to perform these types of analyses and acquire insightful data for biosimilarity assessment is based upon our highly sensitive UPLC MS and IMS methods. PMID- 27260216 TI - Level 5 Lymphadenopathy Warrants Heightened Suspicion for Clinically Significant Pathology. AB - We conclude that patients presenting with level 5 lymphadenopathy should be investigated with heightened clinical vigilance. Our results suggest that up to 80 % will harbour clinically significant pathology requiring further medical treatment, three quarters of which will be malignancy. We report an observational study of histological outcomes of level 5 lymph node biopsies from a regional histopathology department across 5 years. 184 subjects were identified as having a biopsy of a lymph node from the level 5 region within the study period. One hundred and fifty six cases (84.8 %) had clinically significant pathology on final histology requiring further medical treatment. Lymphoma accounted for the highest number of cases (n = 72, 39.1 %), followed by metastatic carcinoma (n = 65, 35.3 %) and granulomatous change (n = 17, 9.2 %). Gender and laterality were not shown to be independent predictors of pathology significance (p > 0.05). PMID- 27260217 TI - Exclusive Primary Lesion of Oral Leishmaniasis with Immunohistochemical Diagnosis. AB - A case of oral leishmaniasis without cutaneous involvement affecting the upper alveolar ridge mucosa/gingiva and the hard palate is reported in a 41-year-old Brazilian man. Microscopic examination disclosed scarce amastigotes and the definitive diagnosis was facilitated by immunohistochemical analysis. The clinical presentation of this lesion is unusual and underlies the importance of considering leishmaniasis in the differential diagnosis of oral lesions, especially in endemic areas. A literature review of the cases of mucosal leishmaniasis with exclusive primary lesions of the oral mucosa was also performed. PMID- 27260218 TI - [Jejunal perforation secondary to pulmonary mucoepidermoid carcinoma metastasis. Case report and review]. AB - BACKGROUND: The first reported case of intestinal perforation secondary to metastatic lung carcinoma was reported in 1957. Intestinal metastases are present in up to 1.8% of the cases, with small bowel obstruction as the most common clinical presentation. CLINICAL CASE: An 89 year-old male, who was diagnosed with a high-grade pulmonary mucoepidermoid tumour 2 months previously. The patient was admitted to the hospital for 3 days due to diffuse colic abdominal pain of moderate to severe intensity, accompanied by nausea and gastric vomiting, as well as 2 episodes of bloody bowel movements. On physical examination, the patient was noted to have tachycardia and tachypnoea, as well as clinical signs of acute abdomen. He had white cells of 24,900 per mm3, and 87% neutrophils. Exploratory laparotomy was performed, which showed a bowel perforation associated with a tumour mass 15cm beyond the angle of Treitz. Bowel resection and primary anastomosis were performed. The histopathological analysis reported the diagnosis of a high-grade mucoepidermoid tumour with small bowel and mesentery with disease free surgical margins. Unfortunately the patient had a fatal outcome secondary to hospital-acquired pneumonia. CONCLUSION: The cases of metastases to small bowel are extremely rare, and to our knowledge this is first case reported in Mexico. The patient described went to the emergency room with gastrointestinal bleed and intestinal perforation that required urgent surgical intervention with small bowel resection and primary anastomosis. Unfortunately the patient died secondary to hospital acquired pneumonia. PMID- 27260219 TI - What is the effect of treating secondary lymphedema after breast cancer with complete decongestive physiotherapy when the bandage is replaced with Kinesio Textape? - A pilot study. AB - PURPOSE: Secondary lymphedema (SL) following breast cancer is a well-known complication following surgery or radiation. SL may result in loss of functional ability, cosmetic deformities, physical discomfort, recurrent episodes of erysipelas, and psychological distress. There is no evidence as to what is the most effective treatment for SL. METHODS: This randomized controlled pilot study included 10 patients treated for SL following breast cancer. The patients were included and screened for SL by a physiotherapist. They were randomized to treatment with CDP with Kinesio Textape or bandage for 4 weeks. Endpoints were quality of life, circumference of the arm, costs, and working environment for the physiotherapist. RESULTS: The two groups were comparable according to baseline data. Outcomes on quality of life, costs, and working environment for the physiotherapist; the treatment with CDP with tape was superior to the CDP with bandage treatment. In regard to reducing the circumference there was no difference. CONCLUSIONS: This randomized controlled pilot study shows that CDP with tape can be an alternative to CDP with bandage. The quality of life is higher, the economy and working environment is better, and the effect measured by circumference is comparable. More RCTs are required to increase the evidence for CDP with tape. IMPLICATIONS: Treating lymphedema with CDP with tape after breast cancer is a good alternative to CDP with bandage and makes it possible to treat more patients with less resources. PMID- 27260221 TI - The evolution of sports participation guidelines and the influence of genotype phenotype correlation in long QT syndrome. AB - Congenital Long QT Syndrome (LQTS) results in abnormal ventricular repolarization in patients with otherwise structurally normal hearts. Following the initial clinical descriptions of LQTS, there has been a great deal of investigation into the genetic etiology and pathophysiology of these entities, with the goal of improved screening tools and understanding of associated risks. Through this work, heart rhythm experts continue to revise their recommendations regarding sports eligibility. We review the evolution of sports participation recommendations for LQTS. PMID- 27260220 TI - EGFR-targeted Chimeras of Pseudomonas ToxA released into the extracellular milieu by attenuated Salmonella selectively kill tumor cells. AB - Tumor-targeted Salmonella VNP20009 preferentially replicate within tumor tissue and partially suppress tumor growth in murine tumor models. These Salmonella have the ability to locally induce apoptosis when they are in direct contact with cancer cells but they lack significant bystander killing, which may correlate with their overall lack of antitumor activity in human clinical studies. In order to compensate for this deficiency without enhancing overall toxicity, we engineered the bacteria to express epidermal growth factor receptor (EGFR) targeted cytotoxic proteins that are released into the extracellular milieu. In this study, we demonstrate the ability of the Salmonella strain VNP20009 to produce three different forms of the Pseudomonas exotoxin A (ToxA) chimeric with a tumor growth factor alpha (TGFalpha) which results in its producing culture supernatants that are cytotoxic and induce apoptosis in EGFR positive cancer cells as measured by the tetrazolium dye reduction, and Rhodamine 123 and JC-10 mitochondrial depolarization assays. In addition, exchange of the ToxA REDLK endoplasmic reticulum retention signal for KDEL and co-expression of the ColE3 lysis protein resulted in an overall increased cytotoxicity compared to the wild type toxin. This approach has the potential to significantly enhance the antitumor activity of VNP20009 while maintaining its previously established safety profile. Biotechnol. Bioeng. 2016;113: 2698-2711. (c) 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc. PMID- 27260222 TI - Transient Receptor Potential Channels in Microglia: Roles in Physiology and Disease. AB - Microglia modulate the nervous system cellular environment and induce neuroprotective and neurotoxic effects. Various molecules are involved in these processes, including families of ion channels expressed in microglial cells, such as transient receptor potential (TRP) channels. TRP channels comprise a family of non-selective cation channels that can be activated by mechanical, thermal, and chemical stimuli, and which contribute to the regulation of intracellular calcium concentrations. TRP channels have been shown to be involved in cellular processes such as osmotic regulation, cytokine production, proliferation, activation, cell death, and oxidative stress responses. Given the significance of these processes in microglial activity, studies of TRP channels in microglia have focused on determining their roles in both neuroprotective and neurotoxic processes. TRP channel activity has been proposed to play an important function in neurodegenerative diseases, ischemia, inflammatory responses, and neuropathic pain. Modulation of TRP channel activity may thus be considered as a potential therapeutic strategy for the treatment of various diseases associated with alterations of the central nervous system (CNS). In this review, we describe the expression of different subfamilies of TRP channels in microglia, focusing on their physiological and pathophysiological roles, and consider their potential use as therapeutic targets in CNS diseases. PMID- 27260223 TI - Zika Virus Infection and Development of a Murine Model. AB - In view of the recent outbreak of Zika virus (ZIKV), there is an urgent need to investigate the pathogenesis of the symptoms associated with ZIKV infection. Since the first identification of the virus in 1947, the pathologies associated with ZIKV infection were thought to be limited with mild illness that presented fever, rashes, muscle aches, and weakness. However, ZIKV infection has been shown to cause Guillain-Barre Syndrome, and numerous cases of congenital microcephaly in children have been reported when pregnant females were exposed to the virus. The severity and the rate of spread of ZIKV in the last year has drawn alarming interest among researchers to investigate murine models to study viral pathogenesis and develop candidate vaccines. A recent study by Lazear and colleagues, in the May 2016 issue of cell host and microbe, is an effort to study the pathogenesis of contemporary and historical virus strains in various mouse models. PMID- 27260224 TI - FTO Genotype Interacts with Improvement in Aerobic Fitness on Body Weight Loss During Lifestyle Intervention. AB - OBJECTIVE: Not every participant responds with a comparable body weight loss to lifestyle intervention, despite the same compliance. Genetic factors may explain parts of this difference. Variation in fat mass and obesity-associated gene (FTO) is the strongest common genetic determinant of body weight. The aim of the present study was to evaluate the impact of FTO genotype differences in the link between improvement of fitness and reduction of body weight during a lifestyle intervention. METHODS: We genotyped 292 healthy subjects for FTO rs8050136. Participants underwent a 9-month lifestyle intervention. Before and after intervention, aerobic fitness was tested by bicycle (VO2max) and treadmill spiroergometry (individual anaerobic threshold (IAT), subgroup of N = 192). RESULTS: Participants lost body weight (p < 0.0001) independent of FTO genotype (p = 0.5). There was a significant correlation between improvement in VO2max and decrease in body weight (p < 0.0001). FTO genotype interacted with this relationship (p = 0.0042 for VO2max, p = 0.0049 for IAT). When stratifying the cohort according to their improvement in VO2max, FTO obesity-risk A-allele carriers in the higher quartiles of improvement in fitness lost significantly less body weight. CONCLUSIONS: Our data reveal that genetic variation in FTO impacts on body weight reduction during lifestyle intervention only in subjects with marked improvement in aerobic fitness. PMID- 27260240 TI - Erratum to: Moderate and Vigorous Intensity Exercise During Pregnancy and Gestational Weight Gain in Women with Gestational Diabetes. PMID- 27260225 TI - The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays. AB - Establishing a rat model suitable for gamma-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, gamma-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to gamma-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co localization of p-ATM or p-DNA-PKcs with gamma-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of gamma-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of gamma-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced gamma-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding gamma-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of gamma-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of gamma-H2AX biodosimetry for dose assessment in humans. ATM and DNA PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of gamma-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies. PMID- 27260242 TI - Perceived Autonomy Support and Behavioral Engagement in Physical Education: Comment on Yoo (2015). AB - The role of emotion as moderator of the relationships between perceived autonomy supportive behavior and autonomous motivation and between motivation and behavioral engagement in physical education are discussed. PMID- 27260241 TI - Hajj vaccinations-facts, challenges, and hope. AB - Vaccination is an effective preventive measure that has been used in the unique Hajj pilgrimage setting to control the transmission of infectious diseases. The current vaccination policy applied during Hajj is reviewed herein, highlighting the effectiveness of the approaches applied and identifying research gaps that need to be filled in order to improve the development and dissemination of Hajj vaccination strategies. PMID- 27260243 TI - Non-Invasive, Focal Disconnection of Brain Circuitry Using Magnetic Resonance Guided Low-Intensity Focused Ultrasound to Deliver a Neurotoxin. AB - Disturbances in the function of neuronal circuitry contribute to most neurologic disorders. As knowledge of the brain's connectome continues to improve, a more refined understanding of the role of specific circuits in pathologic states will also evolve. Tools capable of manipulating identified circuits in a targeted and restricted manner will be essential not only to expand our understanding of the functional roles of such circuits, but also to therapeutically disconnect critical pathways contributing to neurologic disease. This study took advantage of the ability of low-intensity focused ultrasound (FUS) to transiently disrupt the blood-brain barrier (BBB) to deliver a neurotoxin with poor BBB permeability (quinolinic acid [QA]) in a guided manner to a target region in the brain parenchyma. Ten male Sprague-Dawley rats were divided into two groups receiving the following treatments: (i) magnetic resonance-guided FUS + microbubbles + saline (n = 5), or (ii) magnetic resonance-guided FUS + microbubbles + QA (n = 5). Systemic administration of QA was well tolerated. However, when QA and microbubbles were systemically administered in conjunction with magnetic resonance-guided FUS, the BBB was disrupted and primary neurons were destroyed in the targeted subregion of the hippocampus in all QA-treated animals. Administration of vehicle (saline) together with microbubbles and FUS also disrupted the BBB but did not produce neuronal injury. These findings indicate the feasibility of non-invasively destroying a targeted region of the brain parenchyma using low-intensity FUS together with systemic administration of microbubbles and a neurotoxin. This approach could be of therapeutic value in various disorders in which disturbances of neural circuitry contribute to neurologic disease. PMID- 27260244 TI - Increased Effects of Extracorporeal Shock Waves Combined with Gentamicin against Staphylococcus aureus Biofilms In Vitro and In Vivo. AB - An implant-associated bacterial infection is one of the most common and costly complications of orthopedic surgery. Once biofilms develop, it is extremely difficult to cure infections with antimicrobial agents. High-energy extracorporeal shock wave (ESW) treatment has been used for orthopedic-related diseases and has been found to be an effective bactericidal agent that is tolerable both in vitro and in vivo. The broad-spectrum antibiotic gentamicin exhibits bactericidal activity against Staphylococcus aureus, and bacterial resistance to gentamicin is lower. We tested the effectiveness of gentamicin in combination with ESW treatment against S. aureus biofilms in vivo and in vitro. The spread plate method, crystal violet staining, confocal laser scanning microscopy, scanning electron microscopy and microbiologic evaluation were used to compare the effects of combined treatment with those of either treatment alone. The results revealed statistically significant differences between the group treated with ESWs combined with gentamicin and all other groups. Our findings indicate that use of the combination of ESWs with gentamicin is more effective against S. aureus biofilms in vitro and in vivo. PMID- 27260245 TI - Carotid Atherosclerotic Plaque Alters the Direction of Longitudinal Motion in the Artery Wall. AB - Longitudinal motion of the artery, a cyclical, bidirectional movement of the wall in the long axis of the artery, has recently gained interest in the characterization of artery function. The aim of this study was to evaluate longitudinal motion in patients with internal carotid atherosclerotic plaques. Speckle tracking ultrasound was used to assess common carotid artery wall motion in 12 patients with carotid plaque causing either moderate (50%-79%) or severe (80%-99%) stenosis based on the North American Carotid Endarterectomy Trial, and 23 healthy participants. Although healthy individuals were found to have a retrograde wall motion pattern, a distinct anterograde pattern was noted with plaque presence. Importantly, patients with severe plaque stenosis had greater anterograde motion (0.53 +/- 0.36 mm) than those with moderate stenosis (0.17 +/- 0.15 mm) (p < 0.05), likely owing to high wall shear stresses associated with greater peak systolic velocities at the site of stenosis (severe: 342.0 +/- 99.4 cm/s, moderate: 177.5 +/- 31.2 cm/s, p < 0.01). There were no differences in peak systolic velocities at plaque-free segments between plaque groups (severe: 80.2 +/- 24.8 cm/s, moderate: 92.7 +/- 23.0 cm/s). Blood flow at stenotic areas better predicted motion than plaque-free segments. We conclude that the presence of carotid plaque can have significant influence on longitudinal motion, with significantly greater anterograde displacements with increased stenosis. Future studies are needed to further investigate carotid artery wall mechanics. PMID- 27260247 TI - Heart rate regulation during cycle-ergometer exercise via event-driven biofeedback. AB - This paper is devoted to the problem of regulating the heart rate response along a predetermined reference profile, for cycle-ergometer exercises designed for training or cardio-respiratory rehabilitation. The controller designed in this study is a non-conventional, non-model-based, proportional, integral and derivative (PID) controller. The PID controller commands can be transmitted as biofeedback auditory commands, which can be heard and interpreted by the exercising subject to increase or reduce exercise intensity. However, in such a case, for the purposes of effectively communicating to the exercising subject a change in the required exercise intensity, the timing of this feedback signal relative to the position of the pedals becomes critical. A feedback signal delivered when the pedals are not in a suitable position to efficiently exert force may be ineffective and this may, in turn, lead to the cognitive disengagement of the user from the feedback controller. This note examines a novel form of control system which has been expressly designed for this project. The system is called an "actuator-based event-driven control system". The proposed control system was experimentally verified using 24 healthy male subjects who were randomly divided into two separate groups, along with cross validation scheme. A statistical analysis was employed to test the generalisation of the PID tunes, derived based on the average transfer functions of the two groups, and it revealed that there were no significant differences between the mean values of root mean square of the tracking error of two groups (3.9 vs. 3.7 bpm, [Formula: see text]). Furthermore, the results of a second statistical hypothesis test showed that the proposed PID controller with novel synchronised biofeedback mechanism has better performance compared to a conventional PID controller with a fixed-rate biofeedback mechanism (Group 1: 3.9 vs. 5.0 bpm, Group 2: 3.7 vs. 4.4 bpm, [Formula: see text]). PMID- 27260246 TI - Ex Vivo Porcine Arterial and Chorioallantoic Membrane Acoustic Angiography Using Dual-Frequency Intravascular Ultrasound Probes. AB - The presence of blood vessels within a developing atherosclerotic plaque has been found to be correlated with increased plaque vulnerability and ensuing cardiac events, however, detection of coronary intraplaque neovascularization poses a significant challenge in the clinic. We describe here a new in vivo intravascular ultrasound imaging method using a dual-frequency transducer to visualize contrast flow in microvessels with high specificity. This method uses a specialized transducer capable of exciting contrast agents at a low frequency (5.5 MHz) while detecting their nonlinear superhamonics at a much higher frequency (37 MHz). In vitro evaluation of the approach was performed in a microvascular phantom to produce 3-D renderings of simulated vessel patterns and to determine image quality metrics as a function of depth. Furthermore, we describe the ability of the system to detect microvessels both ex vivo using porcine arteries and in vivo using the chorioallantoic membrane of a developing chicken embryo with optical confirmation. Dual-frequency contrast-specific imaging was able to resolve vessels similar in size to those found in vulnerable atherosclerotic plaques at clinically relevant depths. The results of this study add to the support for further evaluation and translation of contrast-specific imaging in intravascular ultrasound for the detection of vulnerable plaques in atherosclerosis. PMID- 27260248 TI - Changing etiologies and outcome of liver failure in Southwest China. AB - BACKGROUND: The prognosis of liver failure depends greatly on the underlying cause, and there were few data about the prognosis, etiologies or trigger factors of liver failure in China based on long-term and large samples cohorts. METHODS: We screened out 3171 liver failure cases from 25467 patients hospitalized in our department between 2000 and 2012 according to Chinese criteria, and determined their etiologies and prognosis. RESULTS: 97.3 % cases were associated with at least one of 25 identified factors. The 3 leading etiologies were HBV (91.6 %), alcohol (18.1 %) and antiviral therapy (AVT) related hepatitis B flares (6.7 %). Acute-on-chronic liver failure (ACLF) accounted for 92.1 % of all cases. 96.5 % ACLF cases were associated with HBV, in which the percentage of AVT related flares increased from 0 % in 2000 up to 11.5 % in 2012, and hepatitis virus superinfection declined from peak 19.3 % in 2002 down to 2.5 % in 2012. Three month spontaneous survival (SS) rate of 3171 cases was 31.4 %, but improved from 17.4 % in 2000 up to 40.4 % in 2012. SS was significantly different among various etiological groups (P = 0.000). In HBV related liver failure aged 25 to 54 years, males accounted for 87.6 %, and had a progressively decreased SS with increasing age. From 25 to 54 years, SS was lower in male than in female HBV related liver failure, and having significant difference in cases of ages 40 to 44 years (27.6 % versus 50.9 %, P = 0.001). CONCLUSION: Etiologies of liver failure were numerous and varied in southwest China. HBV was the most leading cause of liver failure, especially in ACLF. AVT related flares had become the third leading cause of ACLF. The prognosis of liver failure remained poor, but had markedly improved in recently 3 years. Middle-aged male HBsAg carriers had an extremely higher risk for liver failure and worse prognosis compared to female. 1. Etiologies of liver failure were numerous and varied in southwest China. HBV infection is the main cause of liver failure in southwest China, especially the major cause of ACLF. Antiviral related liver failure, especially the NUCs withdrawal induced ACLF were extremely increased, which has replaced the superinfection as the third important cause of HBV-ACLF. 2. The prognosis of liver failure is still poor, but the spontaneous survival rate showed a trend of steady rise in recent years. The prognosis of patients with liver failure caused by different causes also exists certain difference, the more damage factors bulls the worse prognosis. 3. The prognosis of the HBV and HCV reactivation induced by the steroids was poor.Interferon treatment of CHB in ACLF although rare, but should be taken into consideration seriously. 4. Patients with liver failure caused by different etiologies showed larger differences of gender and age distribution. Gender and age are the important factors with the occurrence and prognosis of HBV-ACLF. PMID- 27260249 TI - Decrease in antithrombin III and prothrombin serum levels contribute to coagulation disorders during leptospirosis. AB - Pathogenic bacteria of the genus Leptospira are the causative agent of leptospirosis, an emergent infectious disease that affects humans and animals worldwide. Severe forms of the disease in humans include jaundice, multiple organ failure and intense haemorrhage. Up to now, mechanisms associated with the haemorrhage foci are poorly understood. We report in this work that, despite the low levels of antithrombin III in convalescent human serum samples, virulent, culture-attenuated and saprophyte strains of Leptospira are unable to bind and/or degrade this thrombin inhibitor, suggesting an indirect mechanism of pathogenesis. Lower levels of prothrombin were found in serum samples at the onset and convalescent phase of the disease when compared to normal human sera. The concomitant decreased levels of antithrombin III and prothrombin suggest a process of stimulated coagulation, which is corroborated by the increase of prothrombin fragment F1+2 in the serum samples. Data obtained with hamsters experimentally infected with virulent Leptospira interrogans serovars Kennewicki and Canicola strongly point out that haemorrhage is correlated with decreased levels of thrombin inhibitors and prothrombin. Activated coagulation might lead to an overconsumption of coagulation factors ultimately leading to bleeding and organ failure. PMID- 27260250 TI - Autophagy and Alzheimer's Disease. AB - Autophagy is an essential degradation pathway in clearing abnormal protein aggregates in mammalian cells and is responsible for protein homeostasis and neuronal health. Several studies have shown that autophagy deficits occurred in early stage of Alzheimer's disease (AD). Autophagy plays an important role in generation and metabolism of beta-amyloid (Abeta), assembling of tau and thus its malfunction may lead to the progress of AD. By considering the above evidences, autophagy may be a new target in developing drugs for AD. So far, a number of mammalian target of rapamycin (mTOR)-dependent and independent autophagy modulators have been identified to have positive effects in AD treatment. In this review, we summarized the latest progress supporting the role for autophagy deficits in AD and the potential therapeutic effects of autophagy modulators in AD. PMID- 27260251 TI - Osteoporotic thoracolumbar junctional fracture accompanied by spinous process fracture without posterior ligament injury: its clinical and radiologic significances. AB - PURPOSE: To assess the clinical and radiologic outcome of osteoporotic thoracolumbar junctional fracture accompanied by spinous process fracture (SPF) without posterior ligament injury. METHODS: A total of 391 patients with single level osteoporotic thoracolumbar junctional (T10-L2) fracture were selectively enrolled. The patients were divided into two groups by absence (group I) or presence (group II) of SPF. Clinical and radiologic parameters were compared between the two groups. RESULTS: Group I comprised of 332 patients with only vertebral body fracture, and group II comprised of 59 patients with both vertebral body and SPFs. In all cases of group II, SPFs were located just one level above the fractured vertebral body, and the injury of the posterior ligament was not found. At the time of injury, group II patients showed worse outcomes in anterior vertebral body compression percentage, kyphotic Cobb angle, cranial disk status, and the rate of the initial neurologic injury. Kyphotic alignment changes during 1-year follow-up were compared between the conservative subgroups of groups I and II. At the time of injury, there were no statistical differences in anterior vertebral body compression percentage and Cobb angle between the two conservative subgroups. However, the difference was significant after 1-year follow-up. Comparison of kyphotic alignment change at 12 months after diagnosis within group II was done according to the treatment method. Vertebroplasty subgroup in group II did not show benefit even in preventing such kyphotic alignment change, whereas instrumentation subgroup in group II showed lordotic alignment restoration despite more severe kyphotic alignment at the time of injury. CONCLUSIONS: Osteoporotic thoracolumbar junctional fracture accompanied by spinous process fracture without posterior ligament injury represented more severe injury with flexion forces on the anterior column and tensile forces on the posterior column, and was related with more severe posttraumatic kyphotic changes during the 12-month follow-up. PMID- 27260252 TI - A formative study to inform mHealth based randomized controlled trial intervention to promote exclusive breastfeeding practices in Myanmar: incorporating qualitative study findings. AB - BACKGROUND: Undernutrition is a major concern for Myanmar children with low exclusive breastfeeding rate (24%). A formative study was conducted to explore the perceptions and practices relating to exclusive breastfeeding, and barriers and facilitators to using mobile communications for exclusive breastfeeding counselling. The results inform the design of a randomized control trial to promote exclusive breastfeeding practices among Myanmar mothers. METHODS: We conducted twenty in-depth interviews with pregnant women and accompanying family members attending an antenatal clinic at the Central Women's Hospital, Yangon, seven key-informant interviews and one focus group discussion with fifteen service providers such as nurses, doctors, managers and staff from the National Nutrition Centre, Department of Health, United Nations Children's Fund International and National Non-Government Organizations and Ooredoo, a private mobile company. RESULTS: Widespread practices of feeding water, honey, infant formula and semi-solid food were reported to be existed in the community before the child reaches four months, mostly influenced by grandmothers from both sides. All couples knew breast milk was good for baby and intended to breastfeed, though limited understanding of the term exclusive breastfeeding was reported. Perception that breast milk alone was not sufficient to provide all nutrients needed for the first six months of baby's life, mother had insufficient milk supply or breast problems, mother's back to work and grandmothers' influence emerged as barriers to breastfeed exclusively for six months. All women knew how to make basic phone calls, majority could read mobile text message in Burmese and possess mobile phones while a few of them shared phones with their husbands. All couples preferred to receive text messages 2-3 times per week in the evening. Institutional staff suggested messages to be simple, easily understandable and culturally appropriate. Perceived barriers included limited mobile network coverage, affordability of mobile handset and phone bills, literacy and community familiarity with text messages. All respondents welcomed the idea of planned intervention. CONCLUSION: We incorporated findings to develop messages and determine the modality, inclusion criteria and tailored with gestation and child age, to be delivered in the randomized controlled trial intervention. PMID- 27260253 TI - Molecular detection of tick-borne protozoan parasites in a population of domestic cats in midwestern Brazil. AB - Some tick-borne pathogens that infect domestic cats have been considered emergent in veterinary medicine. Occurrences of Hepatozoon spp., Babesia spp. and Cytauxzoon spp. have been described in several regions of Brazil. This paper offers a comprehensive analysis of the 18S rRNA gene of a Hepatozoon sp. strain detected in domestic cats in the metropolitan area of Cuiaba, in Midwestern Brazil. Based on a molecular analysis, we detected the presence of Hepatozoon species circulating among cats in this region. The aforementioned strain is closely related to other isolates of H. felis detected in wild felids. Moreover, a phylogenetic analysis indicates that this genotype is grouped into a clade of 18S rRNA sequences previously described for the genus Hepatozoon in wild felids around the world. Hepatozoon felis strains detected in cats from Spain and Israel showed, respectively, 98% and 97% identity to our sequence and are clustered on a separate branch of the phylogenetic tree. This finding suggests a high diversity of Hepatozoon genotypes occurring in cats in Europe and South America. None of the analyzed cats were positive for Babesia spp. or Cytauxzoon spp. by PCR analysis. PMID- 27260254 TI - Seeing is believing: the nocturnal malarial mosquito Anopheles coluzzii responds to visual host-cues when odour indicates a host is nearby. AB - BACKGROUND: The immediate aim of our study was to analyse the behaviour of the malarial mosquito Anopheles coluzzii (An. gambiae species complex) near a human host with the ultimate aim of contributing to our fundamental understanding of mosquito host-seeking behaviour and the overall aim of identifying behaviours that could be exploited to enhance sampling and control strategies. RESULTS: Based on 3D video recordings of individual host-seeking females in a laboratory wind-tunnel, we found that despite being a nocturnal species, An. coluzzii is highly responsive to a visually conspicuous object, but only in the presence of host-odour. Female mosquitoes approached and abruptly veered away from a dark object, which suggests attraction to visual cues plays a role in bringing mosquitoes to the source of host odour. It is worth noting that the majority of our recorded flight tracks consisted of highly stereotyped 'dipping' sequences near the ground, which have been mentioned in the literature, but never before quantified. CONCLUSIONS: Our quantitative analysis of female mosquito flight patterns within ~1.5 m of a host has revealed highly relevant information about responsiveness to visual objects and flight height that could revolutionise the efficacy of sampling traps; the capturing device of a trap should be visually conspicuous and positioned near the ground where the density of host-seeking mosquitoes would be greatest. These characteristics are not universally present in current traps for malarial mosquitoes. The characterisation of a new type of flight pattern that is prevalent in mosquitoes suggests that there is still much that is not fully understood about mosquito flight behaviour. PMID- 27260255 TI - David Oliver: The pundits who do doctors down. PMID- 27260257 TI - Making good death more accessible: end-of-life care in the intensive care unit. PMID- 27260256 TI - Characterization of genome-reduced Bacillus subtilis strains and their application for the production of guanosine and thymidine. AB - BACKGROUND: Genome streamlining has emerged as an effective strategy to boost the production efficiency of bio-based products. Many efforts have been made to construct desirable chassis cells by reducing the genome size of microbes. It has been reported that the genome-reduced Bacillus subtilis strain MBG874 showed clear advantages for the production of several heterologous enzymes including alkaline cellulase and protease. In addition to enzymes, B. subtilis is also used for the production of chemicals. To our best knowledge, it is still unknown whether genome reduction could be used to optimize the production of chemicals such as nucleoside products. RESULTS: In this study, we constructed a series of genome-reduced strains by deleting non-essential regions in the chromosome of B. subtilis 168. These strains with genome reductions ranging in size from 581.9 to 814.4 kb displayed markedly decreased growth rates, sporulation ratios, transformation efficiencies and maintenance coefficients, as well as increased cell yields. We re-engineered the genome-reduced strains to produce guanosine and thymidine, respectively. The strain BSK814G2, in which purA was knocked out, and prs, purF and guaB were co-overexpressed, produced 115.2 mg/L of guanosine, which was 4.4-fold higher compared to the control strain constructed by introducing the same gene modifications into the parental strain. We also constructed a thymidine producer by deleting the tdk gene and overexpressing the prs, ushA, thyA, dut, and ndk genes from Escherichia coli in strain BSK756, and the resulting strain BSK756T3 accumulated 151.2 mg/L thymidine, showing a 5.2-fold increase compared to the corresponding control strain. CONCLUSIONS: Genome-scale genetic manipulation has a variety of effects on the physiological characteristics and cell metabolism of B. subtilis. By introducing specific gene modifications related to guanosine and thymidine accumulation, respectively, we demonstrated that genome-reduced strains had greatly improved properties compared to the wild type strain as chassis cells for the production of these two products. These strains also have great potential for the production of other nucleosides and similar derived chemicals. PMID- 27260259 TI - Four situations in which ECMO might have a chance: response to Staudacher et al. PMID- 27260260 TI - Case studies of spinal deformities in ornamental koi, Cyprinus carpio L. AB - This is a study of vertebral deformities in ornamental koi based on computed radiography and skeletons cleaned by dermestid beetles (Dermestes maculatus). All koi developed gradual onset of swimming abnormalities as adults. Extensive intervertebral osteophyte formation correlated with age of fish and was associated with hindquarter paresis in one koi. Vertebral compression and fusion were the most common spinal deformities occurring at multiple sites, similar to findings in other farmed fish. Site-specific spinal deformities were thought to develop due to differences in swimming behaviour and rates of vertebral growth. One koi had offspring with spinal deformities. Spinal deformities are significant problems in both European and Australian food fish hatcheries. The heritability of vertebral deformities in farmed fish is reportedly low unless there is concurrent poor husbandry or nutritional deficiencies. The specific aetiologies for vertebral deformities in koi in this study could not be ascertained. Current knowledge on spinal deformities in the better studied European food fish species suggests multifactorial aetiologies. Future research should include prospective longitudinal studies of larger numbers of koi from hatch and consideration of all potential risk factors such as husbandry, nutrition, temperature, photoperiod and genetics. PMID- 27260258 TI - Continuous renal replacement therapy versus intermittent hemodialysis in intensive care patients: impact on mortality and renal recovery. AB - PURPOSE: The best renal replacement therapy (RRT) modality remains controversial. We compared mortality and short- and long-term renal recovery between patients treated with continuous RRT and intermittent hemodialysis. METHODS: Patients of the prospective observational multicenter cohort database OUTCOMEREATM were included if they underwent at least one RRT session between 2004 and 2014. Differences in patients' baseline and daily characteristics between treatment groups were taken into account by using a marginal structural Cox model, allowing one to substantially reduce the bias resulting from confounding factors in observational longitudinal data analysis. The composite primary endpoint was 30 day mortality and dialysis dependency. RESULTS: Among 1360 included patients with RRT, 544 (40.0 %) and 816 (60.0 %) were initially treated by continuous RRT and intermittent hemodialysis, respectively. At day 30, 39.6 % patients were dead. Among survivors, 23.8 % still required RRT. There was no difference between groups for the primary endpoint in global population (HR 1.00, 95 % CI 0.77-1.29; p = 0.97). In patients with higher weight gain at RRT initiation, mortality and dialysis dependency were significantly lower with continuous RRT (HR 0.54, 95 % CI 0.29-0.99; p = 0.05). Conversely, this technique appeared to be deleterious in patients without shock (HR 2.24, 95 % CI 1.24-4.04; p = 0.01). Six-month mortality and persistent renal dysfunction were not influenced by the RRT modality in patients with dialysis dependence at ICU discharge. CONCLUSION: Continuous RRT did not appear to improve 30-day and 6-month patient outcomes. It seems beneficial for patients with fluid overload, but might be deleterious in the absence of hemodynamic failure. PMID- 27260261 TI - Febrile patients admitted to remote hospitals in Northeastern Kenya: seroprevalence, risk factors and a clinical prediction tool for Q-Fever. AB - BACKGROUND: Q fever in Kenya is poorly reported and its surveillance is highly neglected. Standard empiric treatment for febrile patients admitted to hospitals is antimalarials or penicillin-based antibiotics, which have no activity against Coxiella burnetii. This study aimed to assess the seroprevalence and the predisposing risk factors for Q fever infection in febrile patients from a pastoralist population, and derive a model for clinical prediction of febrile patients with acute Q fever. METHODS: Epidemiological and clinical data were obtained from 1067 patients from Northeastern Kenya and their sera tested for IgG antibodies against Coxiella burnetii antigens by enzyme-linked-immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA) and quantitative real-time PCR (qPCR). Logit models were built for risk factor analysis, and diagnostic prediction score generated and validated in two separate cohorts of patients. RESULTS: Overall 204 (19.1 %, 95 % CI: 16.8-21.6) sera were positive for IgG antibodies against phase I and/or phase II antigens or Coxiella burnetii IS1111 by qPCR. Acute Q fever was established in 173 (16.2 %, 95 % CI: 14.1-18.7) patients. Q fever was not suspected by the treating clinicians in any of those patients, instead working diagnosis was fever of unknown origin or common tropical fevers. Exposure to cattle (adjusted odds ratio [aOR]: 2.09, 95 % CI: 1.73-5.98), goats (aOR: 3.74, 95 % CI: 2.52-9.40), and animal slaughter (aOR: 1.78, 95 % CI: 1.09-2.91) were significant risk factors. Consumption of unpasteurized cattle milk (aOR: 2.49, 95 % CI: 1.48-4.21) and locally fermented milk products (aOR: 1.66, 95 % CI: 1.19-4.37) were dietary factors associated with seropositivity. Based on regression coefficients, we calculated a diagnostic score with a sensitivity 93.1 % and specificity 76.1 % at cut off value of 2.90: fever >14 days (+3.6), abdominal pain (+0.8), respiratory tract infection (+1.0) and diarrhoea (-1.1). CONCLUSION: Q fever is common in febrile Kenyan patients but underappreciated as a cause of community-acquired febrile illness. The utility of Q fever score and screening patients for the risky social-economic and dietary practices can provide a valuable tool to clinicians in identifying patients to strongly consider for detailed Q fever investigation and follow up on admission, and making therapeutic decisions. PMID- 27260262 TI - Efficacy of tocilizumab for psychiatric symptoms associated with relapsing polychondritis: the first case report and review of the literature. AB - Relapsing polychondritis (RP) rarely affected the central nervous system (CNS). If the CNS is involved, it can result in psychiatric manifestations. Patients with RP always respond well to glucocorticoids and immunosuppressants. If the therapies fail, biologics can be given, such as tocilizumab, which is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Until now, there have been no randomized clinical trials to test the safety and efficacy of biologics, no reports of RP with psychiatric disorders as initial symptoms, and no reports of tocilizumab used for psychiatric symptoms due to RP. Here, we report a 60-year-old woman with mania, logomania, hallucinations, cognitive disorder, persecutory delusion, and violent tendency as chief complaints. The application of dexamethasone worsened her psychiatric symptoms. After the first infusion of tocilizumab, she achieved complete remission within one week. During the follow-up period, she sustained serological and psychiatric remission. Our case illustrates the safety and efficacy of tocilizumab for psychiatric symptoms of RP. PMID- 27260263 TI - Pyrodictium delaneyi sp. nov., a hyperthermophilic autotrophic archaeon that reduces Fe(III) oxide and nitrate. AB - A hyperthermophilic, autotrophic iron and nitrate reducer, strain Su06T, was isolated from an active deep-sea hydrothermal vent chimney on the Endeavour Segment in the north-eastern Pacific Ocean. It was obligately anaerobic, hydrogenotrophic and reduced Fe(III) oxide to magnetite and NO3- to N2. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain was more than 97 % similar to other species of the genera Pyrodictium and Hyperthermus. Therefore, overall genome relatedness index analyses were performed to establish whether strain Su06T represents a novel species. For each analysis, strain Su06T was most similar to Pyrodictium occultum PL-19T. Relative to this strain, the average nucleotide identity score for strain Su06T was 72 %, the genome-to-genome direct comparison score was 13-19 % and the species identification score at the protein level was 89 %. For each analysis, strain Su06T was below the species delineation cutoff. Based on its whole genome sequence and its unique phenotypic characteristics, strain Su06T is suggested to represent a novel species of the genus Pyrodictium, for which the name Pyrodictium delaneyi is proposed. The type strain is Su06T (=DSM 28599T=ATCC BAA 2559T). PMID- 27260264 TI - Reimbursements for telehealth services are likely to be lower than non-telehealth services in the United States. AB - Telehealth technologies promise to increase access to care, particularly in underserved communities. However, little is known about how private payer reimbursements vary between telehealth and non-telehealth services. We use the largest private claims database in the United States provided by the Health Care Cost Institute to identify telehealth claims and compare average reimbursements to non-telehealth claims. We find average reimbursements for telehealth services are significantly lower than those for non-telehealth for seven of the ten most common services. For example, telehealth reimbursements for office visits for evaluation and management of established patients with low complexity were 30% lower than the corresponding non-telehealth service. Reimbursements by clinical diagnosis code also tended to be lower for telehealth than non-telehealth claims. Widespread adoption of telehealth may be hampered by lower reimbursements for telehealth services relative to face-to-face services. This may result in lower incentives for providers to invest in telehealth technologies that do not result in significant cost savings to their practice, even if telehealth improves patient outcomes. PMID- 27260265 TI - Microbacterium gilvum sp. nov., isolated from civet faeces. AB - A novel aerobic, non-motile, Gram-positive, rod-shaped actinobacterium, designated YIM 100951(T), was isolated from the faeces of civets (Viverra zibetha) living in the National Nature Protect Region in Selangor, Malaysia. Strain YIM 100951(T) shows high similarities with Microbacterium barkeri DSM 20145(T) (97.6 %), Microbacterium oryzae MB10(T) (97.3 %), Microbacterium lemovicicum ViU22(T) (97.1 %) and Microbacterium indicum BBH6(T) (97.0 %) based on their 16S rRNA genes. However, phylogenetic analysis showed that strain YIM 100951(T) formed a clade with Microbacterium halotolerans YIM 70130(T) (96.7 %), Microbacterium populi 10-107-8(T) (96.7 %) and Microbacterium sediminis YLB-01(T) (96.9 %). DNA-DNA hybridization was carried out between strains YIM 100951(T) and M. barkeri DSM 20145(T), the result showed a value of 23.2 +/- 4.5 %. In addition, some of the physiological, biochemical and chemotaxonomic characteristics of strain YIM 100951(T) are different from the closely related strains. Thus, we suggest that strain YIM 100951(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium gilvum sp. nov. is proposed. The type strain is YIM 100951(T) (=DSM 26235(T) = CCTCC AB 2012971(T)). PMID- 27260266 TI - Pitcher's elbow: medial elbow pain in the overhead-throwing athlete. AB - Overhead athletes subject their elbows to significant valgus stresses throughout the throwing cycle. A steady rise in the number of medial-sided elbow injuries over the years has lead to increased awareness regarding the pathophysiology of the "pitcher's elbow." As our understanding of the functional anatomy and throwing biomechanics has become more sophisticated, we have seen a concurrent improvement in the outcomes associated with managing these injuries. Despite this improvement, continued anatomical and biomechanical research is still needed to further optimize outcomes and return to sport. PMID- 27260267 TI - Complication avoidance with pre-operative screening: insights from the Seattle spine team. AB - Complication rates for complex adult lumbar scoliosis surgery are unacceptably high. Standardized preoperative evaluation protocols have been shown to significantly reduce the likelihood of a spectrum of negative outcomes associated with complex adult lumbar scoliosis surgery. To increase patient safety and reduce complication risk, an entire medical and surgical team should work together to care for adult lumbar scoliosis patients. This article describes preoperative patient evaluation strategies with a particular focus on adult lumbar scoliosis surgery involving six or more levels of spinal fusion. Domains considered include recent preoperative evaluation literature, predictive risk modeling, the appropriate management of medical conditions, and the composition and activities of a multidisciplinary conference review team. An evidence-based comprehensive systematic preoperative surgical evaluation process is described. PMID- 27260268 TI - The Efficacy of Propranolol in Retinopathy of Prematurity and its Correlation with the Platelet Mass Index. AB - PURPOSE: Retinopathy of Prematurity (ROP) is a proliferative vitreoretinopathy which is one of the most frequent causes of blindness in children. In an attempt to find a solution to this important problem in preterm children, the search for new, effective treatment modalities with fewer side effects is underway. In our study, which was planned for this reason, we aimed to investigate the effects of propranolol treatment applied to cases of ROP in various stages during the second phase (known as the neovascularization-hypoxia phase) and to determine the correlation of these effects with the platelet mass index (PMI). METHOD: A total of 171 preterm infants at risk of ROP were selected randomly for inclusion in the study. All of the patients were classified according to their stage of ROP and were divided into control and treatment groups. While the cases in the control group were administered physiological saline solution, those in the treatment group were administered propranolol in the period that corresponded to the second stage of the disease. The thrombocyte and PMI values in the first and second stages of each study group were recorded. RESULTS: A significant difference was found between the control and treatment groups of the stage 2 ROP study subjects. In the stage 2 ROP study group, no significant difference was detected between the control and treatment cases in terms of platelet counts in phase 1 or in the PMI values and the thrombolytic counts in phase 2. On the other hand, in phase 2 of the stage 2 ROP study subjects significant differences were detected between the control and treatment group in terms of PMI values. CONCLUSION: In the study, it was found in the stage 2 ROP study group that propranolol reduced the need for laser photocoagulation significantly. Also, in parallel to the efficacy of propranolol in this study group, a decrease was observed in PMI values. PMID- 27260269 TI - A cool approach to reducing electrode-induced trauma: Localized therapeutic hypothermia conserves residual hearing in cochlear implantation. AB - OBJECTIVE: The trauma caused during cochlear implant insertion can lead to cell death and a loss of residual hair cells in the cochlea. Various therapeutic approaches have been studied to prevent cochlear implant-induced residual hearing loss with limited success. In the present study, we show the efficacy of mild to moderate therapeutic hypothermia of 4 to 6 degrees C applied to the cochlea in reducing residual hearing loss associated with the electrode insertion trauma. APPROACH: Rats were randomly distributed in three groups: control contralateral cochleae, normothermic implanted cochleae and hypothermic implanted cochleae. Localized hypothermia was delivered to the middle turn of the cochlea for 20 min before and after implantation using a custom-designed probe perfused with cooled fluorocarbon. Auditory brainstem responses (ABRs) were recorded to assess the hearing function prior to and post-cochlear implantation at various time points up to 30 days. At the conclusion of the trials, inner ears were harvested for histology and cell count. The approach was extended to cadaver temporal bones to study the potential surgical approach and efficacy of our device. In this case, the hypothermia probe was placed next to the round window niche via the facial recess or a myringotomy. MAIN RESULTS: A significant loss of residual hearing was observed in the normothermic implant group. Comparatively, the residual hearing in the cochleae receiving therapeutic hypothermia was significantly conserved. Histology confirmed a significant loss of outer hair cells in normothermic cochleae receiving the surgical trauma when compared to the hypothermia treated group. In human temporal bones, a controlled and effective cooling of the cochlea was achieved using our approach. SIGNIFICANCE: Collectively, these results suggest that therapeutic hypothermia during cochlear implantation may reduce traumatic effects of electrode insertion and improve conservation of residual hearing. PMID- 27260270 TI - Impact of peripheral hearing loss on top-down auditory processing. AB - The auditory system consists of an intricate set of connections interposed between hierarchically arranged nuclei. The ascending pathways carrying sound information from the cochlea to the auditory cortex are, predictably, altered in instances of hearing loss resulting from blockage or damage to peripheral auditory structures. However, hearing loss-induced changes in descending connections that emanate from higher auditory centers and project back toward the periphery are still poorly understood. These pathways, which are the hypothesized substrate of high-level contextual and plasticity cues, are intimately linked to the ascending stream, and are thereby also likely to be influenced by auditory deprivation. In the current report, we review both the human and animal literature regarding changes in top-down modulation after peripheral hearing loss. Both aged humans and cochlear implant users are able to harness the power of top-down cues to disambiguate corrupted sounds and, in the case of aged listeners, may rely more heavily on these cues than non-aged listeners. The animal literature also reveals a plethora of structural and functional changes occurring in multiple descending projection systems after peripheral deafferentation. These data suggest that peripheral deafferentation induces a rebalancing of bottom-up and top-down controls, and that it will be necessary to understand the mechanisms underlying this rebalancing to develop better rehabilitation strategies for individuals with peripheral hearing loss. PMID- 27260271 TI - Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. AB - BACKGROUND: A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a "gut-brain axis" disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx(r)) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. METHODS: A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. DISCUSSION: The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02708901 . Retrospectively registered: March 4, 2016. PMID- 27260272 TI - Toward refined environmental scenarios for ecological risk assessment of down-the drain chemicals in freshwater environments. AB - Current regulatory practice for chemical risk assessment suffers from the lack of realism in conventional frameworks. Despite significant advances in exposure and ecological effect modeling, the implementation of novel approaches as high-tier options for prospective regulatory risk assessment remains limited, particularly among general chemicals such as down-the-drain ingredients. While reviewing the current state of the art in environmental exposure and ecological effect modeling, we propose a scenario-based framework that enables a better integration of exposure and effect assessments in a tiered approach. Global- to catchment scale spatially explicit exposure models can be used to identify areas of higher exposure and to generate ecologically relevant exposure information for input into effect models. Numerous examples of mechanistic ecological effect models demonstrate that it is technically feasible to extrapolate from individual-level effects to effects at higher levels of biological organization and from laboratory to environmental conditions. However, the data required to parameterize effect models that can embrace the complexity of ecosystems are large and require a targeted approach. Experimental efforts should, therefore, focus on vulnerable species and/or traits and ecological conditions of relevance. We outline key research needs to address the challenges that currently hinder the practical application of advanced model-based approaches to risk assessment of down-the-drain chemicals. Integr Environ Assess Manag 2017;13:233-248. (c) 2016 SETAC. PMID- 27260274 TI - Oral Medicine-the new dental specialty. PMID- 27260273 TI - Acyl Chain Disorder and Azelaoyl Orientation in Lipid Membranes Containing Oxidized Lipids. AB - Oxidized phospholipids occur naturally in conditions of oxidative stress and have been suggested to play an important role in a number of pathological conditions due to their effects on a lipid membrane acyl chain orientation, ordering, and permeability. Here we investigate the effect of the oxidized phospholipid 1 palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC) on a model membrane of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) using a combination of (13)C-(1)H dipolar-recoupling nuclear magnetic resonance (NMR) experiments and united-atom molecular dynamics (MD) simulations. The obtained experimental order parameter SCH profiles show that the presence of 30 mol % PazePC in the bilayer significantly increases the gauche content of the POPC acyl chains, therefore decreasing the thickness of the bilayer, although with no stable bilayer pore formation. The MD simulations reproduce the disordering effect and indicate that the orientation of the azelaoyl chain is highly dependent on its protonation state with acyl chain reversal for fully deprotonated states and a parallel orientation along the interfacial plane for fully protonated states, deprotonated and protonated azelaoyl chains having negative and positive SCH profiles, respectively. Only fully or nearly fully protonated azelaoyl chain are observed in the (13)C-(1)H dipolar-recoupling NMR experiments. The experiments show positive SCH values for the azelaoyl segments confirming for the first time that oxidized chains with polar termini adopt a parallel orientation to the bilayer plane as predicted in MD simulations. PMID- 27260275 TI - The efficacy of botulinum toxin for the treatment of trigeminal and postherpetic neuralgia: a systematic review with meta-analyses. AB - OBJECTIVE: To evaluate the efficacy of a botulinum toxin type A (BoTN-A) in treating trigeminal neuralgia (TN) and postherpetic neuralgia (PHN). STUDY DESIGN: Three databases were searched: Medline, Web of Science, and Cochrane Library. The search was restricted to English-language randomized, placebo controlled trials. Three review authors evaluated the cases for risk of bias. RESULTS: Six studies were eligible for inclusion. Pooled results showed a difference in post-treatment pain intensity of -3.009 (95% confidence interval 4.566 to -1.453; P < .001) in favor of BoTN-A compared with placebo in managing TN or PHN. Of the six studies, five had unclear risk of bias, and one showed high risk. CONCLUSIONS: Although the studies had unclear or high risk of bias, moderate evidence regarding the efficacy of BoTN-A in treating TN and PHN was found. BoTN-A might be an alternative treatment to those patients who are either unable to manage their pain medically or would like adjunct therapy. PMID- 27260276 TI - Etiology and pathogenesis of oral lichen planus: an overview. AB - Oral lichen planus is a noninfectious, chronic inflammatory condition that involves the oral mucosal stratified squamous epithelium and the underlying lamina propria and may be accompanied by skin lesions. This overview describes the current understanding of the immunopathologic mechanisms implicated in oral lichen planus. PMID- 27260277 TI - Ultrastructural evaluation of gingival connective tissue in hereditary gingival fibromatosis. AB - OBJECTIVE: To describe the ultrastructural features of hereditary gingival fibromatosis (HGF) in affected family members and compare microscopic findings with normal gingival (NG) tissue. STUDY DESIGN: Gingival tissue samples from nine patients with HGF from five unrelated families were evaluated by transmission electron microscopy. Nine NG tissue samples were used for comparison. RESULTS: Areas containing collagen fibrils forming loops and folds were observed in both groups, whereas oxytalan fibers were frequently identified in the HGF group. The diameter of collagen fibrils and the interfibrillar space among them were more uniform in the NG group than in the HGF group. Fibroblasts were the most common cells found in both the HGF and NG groups and exhibited enlarged, rough endoplasmic reticulum, mitochondria with well-preserved crests, conspicuous nucleoli, and euchromatic chromatin. Other cells, such as mast cells, plasma cells, and macrophages, were also observed. CONCLUSIONS: HGF tissues had ultrastructural characteristics that were very similar to those of NG tissues. Oxytalan fibers were observed more frequently in the HGF samples than in the NG samples. Other studies of HGF in patients from different families should be performed to better understand the pathogenesis of this hereditary condition. PMID- 27260278 TI - Severity and presence of atherosclerosis signs within the segments of internal carotid artery: CBCT's contribution. AB - OBJECTIVES: This study aims to assess with cone-beam computed tomography the distribution and interrelation of the presence of calcifications along the course of the internal carotid artery and to associate their severity with their allocation within the segments of internal carotid artery, gender, and age. STUDY DESIGN: Using a documented visual scale, 161 cone-beam computed tomography scans were evaluated on the allocation and severity of intracranial calcifications within the segments of the internal carotid artery. RESULTS: Calcifications were detected along the petrous (C2: 11.8%), lacerum (C3: 23.6%), cavernous (C4: 92.5%), and ophthalmic-clinoid (C5/C6: 65.8%) segments. The Friedman test showed significant differences in severity distribution among these segments; the highest degree was found in the C4 segment (P < .05). The Wilcoxon signed-rank test showed no significant differences between calcifications on the right or left side or between severities within the C1 (extracranial) and C5/C6 segments. The Chi-square test showed that the severity and allocation of calcifications are not influenced by gender; it also showed that their severity increases with age (P < .05). CONCLUSIONS: In the cohort studied, the incidence of calcifications increased throughout the C1, C5/C6, and C4 segments. More severe calcifications were found at the C4, C1, and C5/C6 segments in decreasing order but increased with age, regardless of gender. PMID- 27260279 TI - Tissue characterization using optical coherence tomography and cone beam computed tomography: a comparative pilot study. AB - OBJECTIVES: To evaluate the ability of optical coherence tomography (OCT) in differentiating human oral tissues in comparison with cone beam computed tomography. STUDY DESIGN: In this study, we imaged four types of tissues ex vivo: human enamel, human cortical bone, human trabecular bone, and fatty tissue plus water and air by using OCT (Axsun Inc., Billerica, MA). We then developed a method for qualitative and quantitative analyses of the human specimens. The same types of tissues were also imaged using cone beam computed tomography, and gray scale values were measured. RESULTS: The qualitative indices (intensity profile, contour plot, and histogram) for OCT images were able to provide information regarding surface characteristics as well as changes in tissue properties at different interfaces. The quantitative index (pixel intensity values) was also able to render information regarding the distribution and density of the pixels in different samples. A similar pattern was observed in the pixel intensity values and gray-scale values in both imaging modalities. CONCLUSIONS: Within the limitations of this ex vivo pilot study, OCT can reliably differentiate between a range of hard and soft tissues. PMID- 27260280 TI - Reliability of three-dimensional measurements of the upper airway on cone beam computed tomography images. AB - OBJECTIVES: The aim of this study was (1) to assess intra- and interobserver reliability of the localization of anatomic landmarks of the upper airway on cone beam computed tomography (CBCT) images; and (2) to assess intra- and interobserver reliability of the three-dimensional measurements of the upper airway based on these landmarks. STUDY DESIGN: Fifteen NewTom 5G (QR systems, Verona, Italy) CBCT data sets were randomly selected from the archives of the Department of Oral Radiology, Academic Centre for Dentistry (ACTA) at University of Amsterdam and VU University, Amsterdam, The Netherlands. Three observers localized six anatomic landmarks that are relevant for upper airway analysis twice, with a 10-day interval, using 3Diagnosys software (v5.3.1, 3diemme, Cantu, Italy). Subsequently, the observers performed upper airway volume measurement based on those landmarks twice as well, again with a 10-day interval, using Amira software (v4.1, Visage Imaging Inc., Carlsbad, CA). The upper airway measurements also included the minimum cross-sectional area (CSAmin), location of the CSAmin, and anteroposterior and lateral dimensions of the CSAmin. RESULTS: Both intraobserver reliability and interobserver reliability were excellent for the localization of the anatomic landmarks of the upper airway (intraclass correlation coefficients = 0.97-1.00) as well as for the three-dimensional upper airway measurements (intraclass correlation coefficients = 0.78-1.00). CONCLUSIONS: The methodology of landmark localization and upper airway measurements, as used in this study, showed an excellent reliability and can thus be recommended for upper airway analysis on CBCT images. PMID- 27260281 TI - Oral medicine in academia. PMID- 27260282 TI - Comments on "Cone beam computed tomography (CBCT) sialography-an adjunct to salivary gland ultrasonography in the evaluation of recurrent salivary gland swelling". PMID- 27260283 TI - Reply to the queries concerning our recent paper "Cone beam computed tomography (CBCT) sialography-an adjunct to salivary gland ultrasonography in the evaluation of recurrent salivary gland swelling". PMID- 27260284 TI - Ultrasonography in the diagnosis of bone lesions of the jaws: a systematic review. AB - The diagnostic use of ultrasonography in dentistry and maxillofacial surgery has previously been described in the literature. Considering that ultrasonography may be useful for the diagnosis of bone lesions of the jaws, a systematic review was carried out to examine the evidence. This review determined that ultrasonography has been used effectively for the diagnosis of infective and/or inflammatory lesions, cysts, nonodontogenic tumors, odontogenic tumors, and arteriovenous malformations and for the differential diagnosis of lesions of endodontic origin, compared with the gold standard of histologic analysis. Ultrasonography may be a viable adjunct to other special tests for the diagnosis of intraosseous lesions of the jaws, as it is noninvasive and does not involve ionizing radiation exposure of the patient. PMID- 27260285 TI - Amebic liver abscess in children-Experience from Central India. PMID- 27260286 TI - Kluyveromyces marxianus as a host for heterologous protein synthesis. AB - The preferentially respiring and thermotolerant yeast Kluyveromyces marxianus is an emerging host for heterologous protein synthesis, surpassing the traditional preferentially fermenting yeast Saccharomyces cerevisiae in some important aspects: K . marxianus can grow at temperatures 10 degrees C higher than S. cerevisiae, which may result in decreased costs for cooling bioreactors and reduced contamination risk; has ability to metabolize a wider variety of sugars, such as lactose and xylose; is the fastest growing eukaryote described so far; and does not require special cultivation techniques (such as fed-batch) to avoid fermentative metabolism. All these advantages exist together with a high secretory capacity, performance of eukaryotic post-translational modifications, and with a generally regarded as safe (GRAS) status. In the last years, replication origins from several Kluyveromyces spp. have been used for the construction of episomal vectors, and also integrative strategies have been developed based on the tendency for non-homologous recombination displayed by K. marxianus. The recessive URA3 auxotrophic marker and the dominant Kan(R) are mostly used for selection of transformed cells, but other markers have been made available. Homologous and heterologous promoters and secretion signals have been characterized, with the K. marxianus INU1 expression and secretion system being of remarkable functionality. The efficient synthesis of roughly 50 heterologous proteins has been demonstrated, including one thermophilic enzyme. In this mini review, we summarize the physiological characteristics of K. marxianus relevant for its use in the efficient synthesis of heterologous proteins, the efforts performed hitherto in the development of a molecular toolbox for this purpose, and some successful examples. PMID- 27260287 TI - Role of sufficient phosphorus in biodiesel production from diatom Phaeodactylum tricornutum. AB - In order to study the role of sufficient phosphorus (P) in biodiesel production by microalgae, Phaeodactylum tricornutum were cultivated in six different media treatments with combination of nitrogen (N) sufficiency/deprivation and phosphorus sufficiency/limitation/deprivation. Profiles of N and P, biomass, and fatty acids (FAs) content and compositions were measured during a 7-day cultivation period. The results showed that the FA content in microalgae biomass was promoted by P deprivation. However, statistical analysis showed that FA productivity had no significant difference (p = 0.63, >0.05) under the treatments of N deprivation with P sufficiency (N-P) and N deprivation with P deprivation (N P-), indicating P sufficiency in N deprivation medium has little effect on increasing biodiesel productivity from P. triornutum. It was also found that the P absorption in N-P medium was 1.41 times higher than that in N sufficiency and P sufficiency (NP) medium. N deprivation with P limitation (N-P-l) was the optimal treatment for producing biodiesel from P. triornutum because of both the highest FA productivity and good biodiesel quality. PMID- 27260288 TI - Fermented Yupingfeng polysaccharides enhance immunity by improving the foregut microflora and intestinal barrier in weaning rex rabbits. AB - Yupingfeng (YPF) is a kind of Astragali radix-based ancient Chinese herbal supplemented with Atractylodis Macrocephalae Rhizoma and Radix Saposhnikoviae. Increasing evidence has proven the beneficial immunomodulating activity of YPF. However, the action mechanism(s) of it is not known. Here, we explored the immunomodulatory activity of unfermented Yupingfeng polysaccharides (UYP) and fermented Yupingfeng polysaccharides (FYP) obtained using Rhizopus oligosporus SH in weaning Rex rabbits. The results showed that both UYP and FYP exhibited notable growth-promoting and immune-enhancing activities, improvement of the intestinal flora homeostasis, and maintenance of intestinal barrier integrity and functionality. Notably, compared with UYP, FYP effectively enhanced average daily gain, organ indices, interleukin-2 (IL-2), IL-4, IL-10, tumor necrosis factor alpha (TNF-alpha), TLR2, and TLR4 mRNA levels in spleen, IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-alpha, and IFN-gamma protein concentrations in serum, and TLR2 and TLR4 mRNA expressions in the gastrointestinal tract (GIT). Moreover, FYP exhibited greater beneficial effects in improving the intestinal flora, including augment flora diversity and the abundance of cellulolytic bacteria, reduction the abundance of Streptococcus spp. and Enterococcus spp. in the GIT, particularly the foregut and maintaining the intestinal barrier integrity and functionality by upregulating zonula occludens 1, claudin, polymeric immunoglobulin receptor, trefoil factor, and epidermal growth factor mRNA levels in the jejunum and ileum. Our results indicated the immunoenhancement effect of FYP is superior over that of UYP, which is probably related with the amelioration of the intestinal microflora and intestinal barrier in the foregut. PMID- 27260289 TI - Preconditioning of endoplasmic reticulum stress protects against acrylonitrile induced cytotoxicity in primary rat astrocytes: The role of autophagy. AB - This study explored the protective effects of endoplasmic reticulum (ER) stress preconditioning induced by 2-deoxy-d-glucose (2-DG) or oxidized dithiothreitol (DTTox) on acrylonitrile (AN)-induced cytotocity in primary rat astrocytes. Cells were pretreated with 2-DG or DTTox for different times at various concentration. Next, astrocytes were treated with 2.5mM AN for an additional 12h. Cell viability and cytotoxicity were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) leakage, respectively. Reactive oxygen species (ROS) and mitochondrial membrane potential (DeltaPsim) were determined. Expression of glucose-regulated protein 78 (GRP78), phosphorylated-eukaryotic translation initiation factor 2alpha (p eIF2alpha), microtubule-associated protein light chain 3 (LC3), P62, and Beclin1 were used to assess autophagy. In addition, 3-methyadenine (3-MA), an autophagy specific inhibitor, was used to assess the role of autophagy in ER stress preconditioning-induced protection against AN cytotoxicity. The results showed that AN alone significantly decreased astrocytic viability and enhanced cytotoxicity. Compared to the AN-alone group, preconditioning with 2-DG or DTTox significantly increased cell viability and reduced cytotoxicity to indistinguishable levels. Decreased ROS generation and increased DeltaPsim were also inherent to ER stress preconditioning with these compounds. Furthermore, autophagy was activated by both 2-DG and DTTox. Blockage of autophagy attenuated the protection afforded by 2-DG or DTTox preconditioning in AN-treated astrocytes. These results establish that ER stress preconditioning affords cellular protection against AN, and that activation of autophagy mediates the cytoprotection. Modulation of ER stress and resultant activation of autophagy may be a novel target for to ameliorate AN toxicity. PMID- 27260290 TI - A Practical Guide to Engaging Individuals with Obesity. AB - Obesity is officially recognised as a chronic disease and a top public health priority by several global societies and healthcare bodies. In some European countries, the majority of the adult population is either overweight or obese, with major implications for patient health and healthcare systems. General practitioners (GPs) are well-placed to tackle this epidemic, yet their engagement with patients is fraught with challenges and barriers. These include time limitations, a lack of evidence base, sensitivities around raising the topic of obesity with patients, inadequate availability of supporting local weight loss services, a lack of training for healthcare professionals (HCPs) on the management of obesity and a limited number of effective therapies. A number of steps need to be implemented to promote engagement between GPs and individuals with obesity. This article provides a European perspective on the obstacles that patients face in accessing healthcare services and discusses a variety of approaches for engaging individuals with obesity and facilitating the management of obesity as a chronic disease. PMID- 27260291 TI - Cognition and eating behavior in amyotrophic lateral sclerosis: effect on survival. AB - It is increasingly recognized that metabolic factors influenced by eating behavior, may affect disease progression in neurodegeneration. In frontotemporal dementia (FTD), which shares a significant overlap with Amyotrophic lateral sclerosis (ALS), patients are well known to develop changes in eating behavior. Whether patients with pure ALS and those with cognitive and behavioral changes associated with ALS also develop similar changes is not known. The current study aimed to examine caloric intake, eating behavioral changes, body mass index, and using cox regression analyses survival across the spectrum of 118 ALS-FTD patients (29 pure ALS, 12 ALS-plus and 21 ALS-FTD, 56 behavioral variant FTD), compared with 25 control subjects. The current study found contrary to previous assumptions eating changes are not restricted to FTD, but a spectrum of eating behavioral changes occur in ALS, present in those with pure ALS and worsening as patients develop cognitive changes. ALS patients with cognitive impairment exhibited changes in food preference, with caloric intake and BMI increasing with the development of cognitive/behavioral changes. Both pure ALS and those with cognitive impairment demonstrated increased saturated fat intake. Survival analyses over the mean patient follow-up period of 6.9 years indicated that increasing eating behavioral changes were associated with an improved survival (threefold decrease risk of dying). Changes in eating behavior and metabolism occur in ALS in association with increasing cognitive impairment, perhaps exerting a protective survival influence. These changes provide insights into the common neural networks controlling eating and metabolism in FTD and ALS and provide potential targets to modify disease prognosis and progression. PMID- 27260292 TI - A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings. AB - Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders mainly characterized by progressive spasticity of the lower limbs. Adult case series dominate the literature, and there have been only a few studies in children. The purpose of this study is to describe our experience with pediatric HSP in Greece. We report the clinical and genetic findings in our patients and aim to offer insights into the diagnostic difficulties of childhood-onset disease. A series of 15 Greek children affected by pure HSP underwent extensive diagnostic investigations. Molecular analysis included whole exome sequencing (WES) or consecutive screening of candidate genes ATL1, SPAST, REEP1, and CYP7B1. WES performed in three cases yielded previously reported mutations in ATL1 and CYP7B1, and a variant c.397C>T of unknown significance in SPG7. Candidate gene screening performed in the remaining patients identified previously reported mutations in ATL1 (2), SPAST (2), and REEP1 (1), and two novel mutations, c.1636G>A and c.1413+3_6delAAGT, in SPAST. In six cases, the mutations were inherited from their parents, while in three cases, the mutations were apparently de novo. Our data confirm the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms. De novo occurrence of HSP does not seem to be uncommon. Candidate gene studies guided by diagnostic algorithms and WES seem both to be reasonable genetic testing strategies. PMID- 27260293 TI - Lesional cerebellar epilepsy: a review of the evidence. AB - Classical teaching in epileptology localizes the origins of focal seizures solely in the cerebral cortex, with only inhibitory effects attributed to subcortical structures. However, electrophysiological and neuroimaging studies over the last decades now provide evidence for an initiation of epileptic seizures within subcortical structures. Intrinsic epileptogenicity of hypothalamic hamartoma has already been established in recognition of subcortical epilepsy, whereas a seizure-generating impact of dysplastic cerebellar lesions remains to be clarified. Herein, we examine the supportive evidence and clinical presentation of cerebellar seizures and review therapy options. PMID- 27260294 TI - Antiplatelet drug resistance is associated with early neurological deterioration in acute minor ischemic stroke in the Chinese population. AB - To evaluate the prevalence and risk factors of antiplatelet drug resistance and its association with early neurological deterioration (END) and recurrent ischemic stroke (RIS) in patients with acute minor stroke. Antiplatelet drug resistance was assessed by platelet aggregation assay in 426 patients with minor stroke who were receiving combined treatment of aspirin and clopidogrel. All patients were followed up for 90 days. The primary endpoint of the study was END within 10 days after admission. The secondary endpoints included RIS, myocardial infarction and death during 90 days of treatment. The safety endpoints were intracerebral or extracranial hemorrhagic events. Cox proportional hazard regression analysis was performed to determine the risk factors for the primary endpoint and secondary endpoints. Among the 426 patients, 24.4 % exhibited aspirin resistance, 35.9 % exhibited clopidogrel resistance, and 19.2 % displayed concomitant aspirin and clopidogrel resistance. In multivariate analysis, diabetes mellitus and high level of low density lipoprotein-cholesterol were independent risk factors for aspirin resistance, while diabetes mellitus was the only independent risk factor for clopidogrel resistance. END was observed in 93 (21.8 %) patients. Diabetes mellitus, high fasting blood glucose level, and concomitant aspirin and clopidogrel resistance were independent risk factors for END. RIS was observed in 40 (9.4 %) patients. Diabetes mellitus, hypertension, and concomitant aspirin and clopidogrel resistance were independent risk factors for RIS. Antiplatelet drug resistance is common in acute minor ischemic stroke patients and is associated with END and RIS after acute minor ischemic stroke in the Chinese population. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.chictr.org/ . Unique Identifier: ChiCTR-OCH-14004724. PMID- 27260295 TI - Natalizumab discontinuation is associated with a rebound of cognitive impairment in multiple sclerosis patients. AB - Natalizumab discontinuation is associated with a disease reactivation in multiple sclerosis (MS) patients. Whether this reactivation involves also cognitive functions is not known to date. To assess the persistence of the effect of natalizumab on cognitive functions 1 year after its discontinuation, we compared the longitudinal changes of cognitive performances in two groups of patients. The interrupters, 30 MS patients, have stopped natalizumab due to PML concern, and the continuers, 28 MS patients, continued the treatment. The cognitive impairment index (CII) was used as main outcome measure. As expected, during the natalizumab treatment, we observed a significant reduction of the relapse rate and the number of gadolinium-enhancing lesions along with a reduction of the CII. After 1 year of discontinuation, the beneficial effect on cognitive functions was lost in the interrupters group, as the mean CII increased in comparison with the mean at the end of natalizumab treatment (12.2 +/- 7.9 vs 9.3 +/- 8.1, p < 0.0001). As opposite, in the continuers group, the CII further decreased after an additional year of treatment (8.4 +/- 5.1 vs 9.8 +/- 4.6, p = 0.007). A multivariate logistic regression model revealed as predictors of cognitive worsening male sex, disease duration, and the treatment discontinuation. The worsening of cognitive functions after natalizumab discontinuation goes in parallel with the clinical/radiological disease reactivation. Our data reinforce the hypothesis that, in the short-term, natalizumab exerts its positive impact on cognitive functions by means of its anti-inflammatory properties. PMID- 27260296 TI - Screening tests for aphasia in patients with stroke: a systematic review. AB - Aphasia has a large impact on the quality of life and adds significantly to the costs of stroke care. Early recognition of aphasia in stroke patients is important for prognostication and well-timed treatment planning. We aimed to identify available screening tests for differentiating between aphasic and non aphasic stroke patients, and to evaluate test accuracy, reliability, and feasibility. We searched PubMed, EMbase, Web of Science, and PsycINFO for published studies on screening tests aimed at assessing aphasia in stroke patients. The reference lists of the selected articles were scanned, and several experts were contacted to detect additional references. Of each screening test, we estimated the sensitivity, specificity, likelihood ratio of a positive test, likelihood ratio of a negative test, and diagnostic odds ratio (DOR), and rated the degree of bias of the validation method. We included ten studies evaluating eight screening tests. There was a large variation across studies regarding sample size, patient characteristics, and reference tests used for validation. Many papers failed to report on the consecutiveness of patient inclusion, time between aphasia onset and administration of the screening test, and blinding. Of the three studies that were rated as having an intermediate or low risk of bias, the DOR was highest for the Language Screening Test and ScreeLing. Several screening tools for aphasia in stroke are available, but many tests have not been verified properly. Methodologically sound validation studies of aphasia screening tests are needed to determine their usefulness in clinical practice. PMID- 27260297 TI - Safety and efficacy of dimethyl fumarate in multiple sclerosis: a multi-center observational study. AB - Dimethyl fumarate (DMF) was recently approved for treating patients with relapsing-remitting multiple sclerosis (RRMS) based on two phase III clinical trials demonstrating its efficacy. This prompts the need for demonstrating the clinical efficacy and safety of DMF in the real world. By retrospective analysis of medical records at two German MS centers, 644 MS patients treated with DMF were identified. All were included in a safety analysis, and a subgroup of patients with available efficacy data during previous MS therapies (n = 352) was further analyzed for annualized relapse rate and disability progression assessed by the EDSS. In the overall DMF population studied, the annualized relapse rate decreased from 0.52 at baseline to 0.35, and the annualized disability progression from 0.15 to 0.10. Patients who were switched from interferons or glatiramer acetate to DMF revealed a greater benefit, whereas patients pretreated with more potent immunotherapies did not respond that well. Interestingly, patients with a lymphocyte count >=2000/ul after 0.52 years (mean, SD 0.2) of DMF treatment did not benefit compared to those with lower lymphocyte counts. In total, 22.2 % of the patients withdrew from DMF due to side effects, with gastrointestinal discomfort (12.7 %) and lymphopenia (5.3 %) as most frequently reported reasons. Our study corroborates that DMF is an overall safe and effective drug that reduces relapse rate as well as disability progression in MS patients. Further prospective studies are warranted to establish the additional parameters predicting DMF response, especially in patients switching from other first-line immunotherapies. PMID- 27260298 TI - Long-term effectiveness of a school-based primary prevention program for anorexia nervosa: A 7-to 8-year follow-up. AB - PURPOSE: This is the first study to evaluate the long-term effectiveness of a school-based prevention program in Germany. The aim is to determine the long-term effects of the primary prevention program PriMa (Primary prevention of anorexia nervosa in preadolescent girls) on disordered eating and body self-esteem from childhood to young adulthood. METHODS: PriMa was conducted and successfully evaluated in a quasi-experimental pre-post design with a control group from 2007 to 2008 consisting of 11-13year old girls (N=1508) from Thuringian schools in Germany. Seven to eight years after the intervention, the same cohort (mean age 19.8years) was invited to complete an online survey. Disordered eating (EAT-26), body self-esteem (FBeK) and BMI were assessed via self-report. The response rate at seven-to-eight-year follow-up was very low (7%). Data of N=100 girls were analyzed. RESULTS: Concerning changes in disordered eating, results revealed no significant long-term effect of PriMa seven to eight years after the intervention. During this time, disordered eating remained stable without a significant increase or decrease. Regarding changes in body self-esteem, group courses differed significantly from each other. The results revealed a significant main effect of group, indicating significant differences in changes of body self-esteem between the intervention and the control group. Following the analysis of these changes of body self-esteem over time, it was found that the intervention group revealed an increase of body self-esteem after program participation and remained stable over time. By contrast, the control group revealed a decrease of body self-esteem over time. CONCLUSIONS: Long-term intervention effects of PriMa could be found for body self-esteem but not for disordered eating. The findings suggest that PriMa prevented a decrease of body self-esteem from childhood to young adulthood. For a broader dissemination it is necessary to implement prevention programs consistently in school settings. In order to maintain the prevention effects, it would be interesting to investigate the effects of booster sessions which refresh the programs content on a regular basis. Furthermore, the results of this study revealed the implementation difficulties of primary prevention programs especially concerning the retention of the sample size. PMID- 27260299 TI - Probabilistic noninvasive prediction of wall properties of abdominal aortic aneurysms using Bayesian regression. AB - Multiple patient-specific parameters, such as wall thickness, wall strength, and constitutive properties, are required for the computational assessment of abdominal aortic aneurysm (AAA) rupture risk. Unfortunately, many of these quantities are not easily accessible and could only be determined by invasive procedures, rendering a computational rupture risk assessment obsolete. This study investigates two different approaches to predict these quantities using regression models in combination with a multitude of noninvasively accessible, explanatory variables. We have gathered a large dataset comprising tensile tests performed with AAA specimens and supplementary patient information based on blood analysis, the patients medical history, and geometric features of the AAAs. Using this unique database, we harness the capability of state-of-the-art Bayesian regression techniques to infer probabilistic models for multiple quantities of interest. After a brief presentation of our experimental results, we show that we can effectively reduce the predictive uncertainty in the assessment of several patient-specific parameters, most importantly in thickness and failure strength of the AAA wall. Thereby, the more elaborate Bayesian regression approach based on Gaussian processes consistently outperforms standard linear regression. Moreover, our study contains a comparison to a previously proposed model for the wall strength. PMID- 27260300 TI - The adipokine Chemerin induces lipolysis and adipogenesis in bovine intramuscular adipocytes. AB - The adipokine Chemerin is reported to regulate adipogenesis and glucose homeostasis in vivo and in 3T3-L1 cells. Our team is focused on the role of Chemerin in metabolism and intramuscular adipocyte differentiation because intramuscular fat is the basic material for the formation of marbling in livestock and poultry meat. In this study, bovine intramuscular mature adipocytes were cultured in medium with Chemerin, and the process of lipolysis of mature adipocytes and the adipogenesis of de-differentiated preadipocytes were investigated. The results showed that Chemerin induced significant lipolytic metabolism in intramuscular mature adipocytes, indicated by increased levels of glycerol, FFA, and up-regulated expression of the lipolysis critical factors HSL, LPL, and leptin. Meanwhile, the expressions of adipogenic key factors PPARgamma, C/EBPalpha, and A-FABP were decreased by Chemerin during lipolysis or dedifferentiation in mature adipocytes. The de-differentiated preadipocytes could re-differentiate into mature adipocytes. Intriguingly, the formation of cells' lipid droplets was promoted by Chemerin during preadipocyte differentiation. In addition, mRNA and protein expressions of PPARgamma, C/EBPalpha, and A-FABP were up-regulated by Chemerin during preadipocytes differentiation. These results suggest that Chemerin promotes lipolysis in mature adipocytes and induces adipogenesis during preadipocyte re-differentiation, further indicating a dual role for Chemerin in the deposition of intramuscular fat in ruminant animals. PMID- 27260301 TI - Caffeic acid phenethyl ester enhances TRAIL-mediated apoptosis via CHOP-induced death receptor 5 upregulation in hepatocarcinoma Hep3B cells. AB - Caffeic acid phenethyl ester (CAPE) exhibits various pharmaceutical properties, including anti-bacterial, anti-inflammatory, anti-viral, anti-cancer, and anti oxidative activity. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been a promising anti-cancer agent that preferentially induces cancer cell apoptosis with negligible cytotoxicity toward normal cells. Therefore, the present study investigated whether CAPE promotes TRAIL-mediated cytotoxicity in hepatocarcinoma Hep3B cells. The present study demonstrated that CAPE sensitized TRAIL-mediated cell death in Hep3B carcinoma cells. The percentages of the apoptotic cells and annexin-V(+) cells significantly increased in combined treatment with CAPE and TRAIL (CAPE/TRAIL). Treatment with pancaspase inhibitor, z-VAD-fmk, attenuated CAPE/TRAIL-induced apoptosis, suggesting that the combined treatment triggers caspase-dependent apoptosis. Additionally, we found that CAPE stimulated the expression of death receptor 5 (DR5) and treatment with DR5/Fc chimera protein significantly blocked CAPE/TRAIL-induced apoptosis, which indicates that CAPE/TRAIL stimulated apoptosis through the binding of TRAIL to DR5. Moreover, expression of transcription factor C/EBP homologous protein (CHOP) markedly increased in response to CAPE and transient knockdown of CHOP abolished CAPE/TRAIL-mediated apoptosis. These results suggest that CHOP is a key regulator in CAPE/TRAIL-mediated apoptosis. Taken together, the present study found that CAPE significantly enhanced TRAIL-mediated apoptosis in Hep3B carcinoma cells and suggested that CAPE has promising potential in chemoprevention of hepatocellular carcinomas. PMID- 27260302 TI - Processes of Personality Development in Adulthood: The TESSERA Framework. AB - The current article presents a theoretical framework of the short- and long-term processes underlying personality development throughout adulthood. The newly developed TESSERA framework posits that long-term personality development occurs due to repeated short-term, situational processes. These short-term processes can be generalized as recursive sequence of Triggering situations, Expectancy, States/State expressions, and Reactions (TESSERA). Reflective and associative processes on TESSERA sequences can lead to personality development (i.e., continuity and lasting changes in explicit and implicit personality characteristics and behavioral patterns). We illustrate how the TESSERA framework facilitates a more comprehensive understanding of normative and differential personality development at various ages during the life span. The TESSERA framework extends previous theories by explicitly linking short- and long-term processes of personality development, by addressing different manifestations of personality, and by being applicable to different personality characteristics, for example, behavioral traits, motivational orientations, or life narratives. PMID- 27260303 TI - Expression of importin-alpha isoforms in human nasal mucosa: implication for adaptation of avian influenza A viruses to human host. AB - BACKGROUND: Transportation into the host cell nucleus is crucial for replication and transcription of influenza virus. The classical nuclear import is regulated by specific cellular factor, importin-alpha. Seven isoforms of importin-alpha have been identified in human. The preference of importin-alpha3 of avian influenza virus and -alpha7 isoform of human strains during replication in human cells was previously identified. In addition, both avian and human influenza viruses were shown to use importin-alpha1 isoform for their replication. FINDING: The mRNA levels of importin-alpha1, -alpha3, and -alpha7 isoforms in human respiratory tract was determined by real-time RT-PCR. The results indicate that mRNA level of importin-alpha7 was significantly higher than that of importin alpha1 (p-value < 0.0001) and importin-alpha3 (p-value < 0.0001) isoforms in human nasal mucosa while importin-alpha1 was detected as the highest expression importin-alpha isoform in lung tissues. CONCLUSIONS: These results may explain the preference of importin-alpha7 isoforms in seasonal influenza viruses in human upper respiratory tract and may suggest a selective pressure toward importin alpha7 in human respiratory tract infection of an avian virus. PMID- 27260304 TI - Principles of microRNA Regulation Revealed Through Modeling microRNA Expression Quantitative Trait Loci. AB - Extensive work has been dedicated to study mechanisms of microRNA-mediated gene regulation. However, the transcriptional regulation of microRNAs themselves is far less well understood, due to difficulties determining the transcription start sites of transient primary transcripts. This challenge can be addressed using expression quantitative trait loci (eQTLs) whose regulatory effects represent a natural source of perturbation of cis-regulatory elements. Here we used previously published cis-microRNA-eQTL data for the human GM12878 cell line, promoter predictions, and other functional annotations to determine the relationship between functional elements and microRNA regulation. We built a logistic regression model that classifies microRNA/SNP pairs into eQTLs or non eQTLs with 85% accuracy; shows microRNA-eQTL enrichment for microRNA precursors, promoters, enhancers, and transcription factor binding sites; and depletion for repressed chromatin. Interestingly, although there is a large overlap between microRNA eQTLs and messenger RNA eQTLs of host genes, 74% of these shared eQTLs affect microRNA and host expression independently. Considering microRNA-only eQTLs we find a significant enrichment for intronic promoters, validating the existence of alternative promoters for intragenic microRNAs. Finally, in line with the GM12878 cell line derived from B cells, we find genome-wide association (GWA) variants associated to blood-related traits more likely to be microRNA eQTLs than random GWA and non-GWA variants, aiding the interpretation of GWA results. PMID- 27260305 TI - Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva. AB - When faced with suboptimal growth conditions, Caenorhabditis elegans larvae can enter a diapause-like stage called "dauer" that is specialized for dispersal and survival. The decision to form a dauer larva is controlled by three parallel signaling pathways, whereby a compromise of TGFbeta, cyclic guanosine monophosphate, or insulin/IGF-like signaling (ILS) results in dauer formation. Signals from these pathways converge on DAF-12, a nuclear hormone receptor that triggers the changes required to initiate dauer formation. DAF-12 is related to the vitamin D, liver-X, and androstane receptors, and like these human receptors, it responds to lipophilic hormone ligands. When bound to its ligand, DAF-12 acquires transcriptional activity that directs reproductive development, while unliganded DAF-12 forms a dauer-specifying complex with its interacting protein DIN-1S to regulate the transcription of genes required for dauer development. We report here that din-1S is required in parallel to par-4/LKB1 signaling within the gonad to establish cell cycle quiescence during the onset of the dauer stage. We show that din-1S is important for postdauer reproduction when ILS is impaired and is necessary for long-term dauer survival in response to reduced ILS. Our work uncovers several previously uncharacterized functions of DIN-1S in executing and maintaining many of the cellular and physiological processes required for appropriate dauer arrest, while also shedding light on the coordination of nuclear hormone signaling, the LKB1/AMPK signaling cascade, and ILS/TGFbeta in the control of cell cycle quiescence and tissue growth: a key feature that is often misregulated in a number of hormone-dependent cancers. PMID- 27260306 TI - Logistic regression model can reduce unnecessary artificial liver support in hepatitis B virus-associated acute-on-chronic liver failure: decision curve analysis. AB - BACKGROUND: Several models have been proposed to predict the short-term outcome of acute-on-chronic liver failure (ACLF) after treatment. We aimed to determine whether better decisions for artificial liver support system (ALSS) treatment could be made with a model than without, through decision curve analysis (DCA). METHODS: The medical profiles of a cohort of 232 patients with hepatitis B virus (HBV)-associated ACLF were retrospectively analyzed to explore the role of plasma prothrombin activity (PTA), model for end-stage liver disease (MELD) and logistic regression model (LRM) in identifying patients who could benefit from ALSS. The accuracy and reliability of PTA, MELD and LRM were evaluated with previously reported cutoffs. DCA was performed to evaluate the clinical role of these models in predicting the treatment outcome. RESULTS: With the cut-off value of 0.2, LRM had sensitivity of 92.6 %, specificity of 42.3 % and an area under the receiving operating characteristic curve (AUC) of 0.68, which showed superior discrimination over PTA and MELD. DCA revealed that the LRM-guided ALSS treatment was superior over other strategies including "treating all" and MELD-guided therapy, for the midrange threshold probabilities of 16 to 64 %. CONCLUSIONS: The use of LRM-guided ALSS treatment could increase both the accuracy and efficiency of this procedure, allowing the avoidance of unnecessary ALSS. PMID- 27260307 TI - SPI-9 of Salmonella enterica serovar Typhi is constituted by an operon positively regulated by RpoS and contributes to adherence to epithelial cells in culture. AB - The genomic island 9 (SPI-9) from Salmonella enterica serovar Typhi (S. Typhi) carries three ORFs (STY2876, STY2877, STY2878) presenting 98 % identity with a type 1 secretory apparatus (T1SS), and a single ORF (STY2875) similar to a large RTX-like protein exhibiting repeated Ig domains. BapA, the Salmonella enterica serovar Enteritidis orthologous to S. Typhi STY2875, has been associated with biofilm formation, and is described as a virulence factor in mice. Preliminary in silico analyses revealed that S. Typhi STY2875 ORF has a 600 bp deletion compared with S. Enteritidis bapA, suggesting that S. Typhi STY2875 might be non functional. At present, SPI-9 has not been studied in S. Typhi. We found that the genes constituting SPI-9 are arranged in an operon whose promoter was up regulated in high osmolarity and low pH in a RpoS-dependent manner. All the proteins encoded by S. Typhi SPI-9 were located at the membrane fraction, consistent with their putative role as T1SS. Furthermore, SPI-9 contributed to adherence of S. Typhi to epithelial cells when bacteria were grown under high osmolarity or low pH. Under the test conditions, S. Typhi SPI-9 did not participate in biofilm formation. SPI-9 is functional in S. Typhi and encodes an adhesin induced under conditions normally found in the intestine, such as high osmolarity. Hence, this is an example of a locus that might be designated a pseudogene by computational approaches but not by direct biological assays. PMID- 27260308 TI - Is Telemental Health Services a Viable Alternative to Traditional Psychotherapy for Deaf Individuals? AB - Access to mental health treatment is a vital part of a comprehensive health care plan. Deaf individuals often have difficulty accessing mental health services. Four-hundred twenty-two participants completed an anonymous questionnaire about their perspectives of telemental health services for deaf individuals. Results showed that several variables, such as if the participant was unable to receive another type of psychotherapy and whether the therapist was ASL-fluent, were significantly related to whether the respondent would use TMH. The participants reported that TMH services are a viable option for treating a variety of mental health issues. Telemental health services can act as a bridge between consumers of mental health care and their providers allowing accessible and equitable healthcare opportunities. PMID- 27260310 TI - Influence of anti-adhesive agent on incidence of bile leakage after liver resection: A prospective cohort study. AB - BACKGROUND: Anti-adhesive agents are increasingly used to reduce the incidence of postoperative adhesions following abdominal surgery. Bile leakage after liver resection remains a major cause of postoperative morbidity. The aim of this study was to examine the effect of anti-adhesive agent on bile leakage after liver resection. MATERIALS AND METHODS: 77 patients were enrolled to receive an anti adhesive agent (study group) during liver resection between May 2012 and August 2013. The study group was compared to a match-paired control group. Clinical data were collected including bilirubin concentration in serum and drain fluid and bile leakage rate. In addition, a separate analysis was performed between patients with and without postoperative bile leakage. RESULTS: There was no difference in bile leakage rate or hospital stay between the study group (n = 77) and control group (n = 77). Of the total number of patients (n = 154), there were 29 patients with postoperative bile leak and 125 patients without bile leak. On univariate analysis, patients without history of hepatitis were significantly associated with bile leakage. In addition, liver resection with broader cut surface area was associated with bile leakage. Application of anti-adhesive agent was not associated with bile leakage. On multivariate analysis, resection with broader cut surface area (OR = 2.788, p = 0.026) and patients without history of hepatitis (OR = 5.153, p = 0.039) were significantly associated with bile leakage. CONCLUSIONS: Larger area of cut-surface and patients without history of hepatitis were significant risk factors for bile leakage. The use of anti adhesive agent was not associated with increased risk of bile leakage. PMID- 27260309 TI - Alterations in glucose metabolism proteins responsible for the Warburg effect in esophageal squamous cell carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is the most frequent esophageal tumor in the world. ESCC presents late diagnosis, highly aggressive behavior and poor survival. Changes in tumor cell energy metabolism appear to have a prominent role in malignant transformation. Tumor cells consume glucose avidly and produce lactic acid, even under normoxia. Among the factors that may contribute to the stimulation of glycolysis in tumor cells, there are changes in the glycolytic pathway enzymes such as: pyruvate kinase M1 and M2 (PKM2 and PKM1), hexokinase II (HKII), glucose transporter isoform 1 (GLUT-1), and transcription factor induced by hypoxia (HIF1alpha), responsible for the transcription of proteins cited. The objective of this study is to evaluate the alterations of these proteins and their association with clinicopathological data in ESCC. We performed immunohistochemistry to determine HIF-1alpha, GLUT-1, PKM1, PKM2, HK2 and Ki67 expression in ESCC patients and controls. Also, we used RT-qPCR to evaluated mRNA expression of GLUT-1 in esophageal mucosa of individuals without cancer, but are alcohol drinkers and tobacco smokers. Our results showed the exclusively expression of GLUT-1 in tumors cells and dysplastic samples. We also observed a compartmentalization of the expression of PKM1 and PKM2 in relation to tumor cells and stroma associated to tumor areas. All of the proteins evaluated, excepted GLUT-1, were frequently detected in normal mucosa. No correlations between clinicopathological features and protein expressions were observed. GLUT 1 expression appears in initial tumor lesions and is maintained through ESCC evolution. We reported for the first time PKM1 staining in normal esophagus and ESCC, being mostly present in more differentiated cells. PMID- 27260311 TI - Preoperative assessment of chemotherapeutic associated liver injury based on indocyanine green retention test. AB - BACKGROUND: The aim of the study was to assess the capacity of indocyanine green retention test at 15 min (ICGR15) to predict chemotherapeutic-associated liver injuries (CALI). METHODS: Patients undergoing liver resection for CLM that received preoperative oxaliplatin and/or irintecan-based chemotherapy within 3 months before surgery and scheduled first hepatectomy were considered. RESULTS: 166 out of 983 patients treated between 01/2001 and 04/2014 fulfilled the inclusion criteria. The median number of cycles of preoperative chemotherapy was 6.0 +/- 4.87. Chemotherapy was mainly based on oxaliplatin in 123 (74.1%). Bevacizumab was associated in 51(31%) patients. A total of 102 (61.4%) patients had at least 1 CALI. Grade 2-3 steatosis occurred in 56 (33.7%) patients and steatohepatitis in19(11.5%). Sinusoidal obstructive syndrome (SOS) was presented in 93 (56%) patients. 23(13.8%) patients had nodular regeneration hyperplasia. At multivariate analysis the only predictive factor of ICGR>=10% was age>=65 years (p = 0.001). A median split (ICGR15 = 8%) was used to categorized ICGR15 value. Multivariate analysis showed that age>= 65 [OR 2.530 (CI95% 1.28-4.97) p < 0.001], male sex [OR 2.614 (CI95% 1.31-5.20) p < 0.001], SOS [OR 1.954 (CI95% 1.00-3.81) p = 0.050] and administration of Bevacizumab [OR 2.201 (CI95% 1.07 4.50) p = 0.031] were predictive factors for ICGR>=8%. CONCLUSIONS: ICGR15 test can predict the diagnosis of SOS. High ICGR15 value is more common in elderly male patients and after bevacizumab administration. PMID- 27260312 TI - Comparison of percutaneous endoscopic lumbar discectomy versus open lumbar microdiscectomy for lumbar disc herniation: A meta-analysis. AB - PURPOSE: The purpose of the study is to perform a systematic review and meta analysis to evaluate the clinical results of percutaneous endoscopic lumbar discectomy (PELD) and open lumbar microdiscectomy (OLM) for the treatment of lumbar disc herniation (LDH). METHODS: Randomized controlled trials or non randomized controlled trials published from the time when databases were built to March 2016 that compared the clinical effectiveness of PELD and OLM surgical approaches for the treatment of LDH were acquired by a comprehensive search in four electronic databases (PubMed, EMBASE, Web of Science and Cochrane library). A total of 7 studies (1389 patients) were included in this systematic review and meta-analysis. Pooled mean differences (MD) and odds ratios (OR) and with 95% CIs were calculated for the outcomes. RESULT: The results showed that there were no statistically between the PELD group and OLM group in terms of preoperative VAS BP score (WMD = 0.03; 95% CI: -0.99 to 1.05; P = 0.95), postoperative VAS-BP score (WMD = -0.56; 95% CI: -1.43 to 0.31; P = 0.21), postoperative ODI (WMD = 0.98; 95% CI: -4.96 to 3.00; P = 0.63), complication rate (OR = 1.79; 95% CI: 0.95 to 3.37; P = 0.07) or reoperation rate (OR = 1.44; 95% CI: 0.94 to 2.20; P = 0.09). PELD group was associated with shorter operation time (WMD = -12.83; 95% CI: -24.79 to -0.87; P = 0.04) and hospital stay (WMD = -5.49; 95% CI: -8.63 to 2.35; P = 0.0006). CONCLUSION: The existing evidence indicate that no superiority exists between the two surgical approaches for the treatment of LDH in terms of functional outcome, complication rate and reoperation rate, in spite of that PELD surgical group can achieve shorter operation time and hospital stay than OLM surgical group. PMID- 27260313 TI - Towards a standardized informed consent procedure for live donor nephrectomy: What do surgeons tell their donors? AB - INTRODUCTION: Living kidney donors comprise a unique group of "patients", undergoing an operation for the benefit of others. The informed consent process is therefore valued differently. Although this is a team effort, the surgeon is responsible for performing the donor nephrectomy, and often the one held accountable, should adverse events occur. Although there is some consensus on how the informed consent procedure should be arranged, practices vary. The aim of this study was to evaluate the surgical informed consent procedure for live donor nephrectomy, with special regards to disclosure of complications. METHODS: A web based survey was sent to all kidney transplant surgeons (n = 50) in eight transplant centers with questions regarding the local procedure and disclosure of specific details. RESULTS: Response rate was 98% (n = 49), of which 32 (65%) were involved in living donor education; overall, transplant- (50%), vascular- (31%), and abdominal surgeons (13%), and urologists (6%) performed donor nephrectomies in the eight centers. Informed consent procedures varied, ranging from assumed to signed consent. Bleeding was the only complication every surgeon mentioned. Risk of death was always mentioned by 16 surgeons (50%), sometimes by 13 (41%), three surgeons (9%) never disclosed this disastrous complication. Reported mortality rates ranged from 0.003% to 0.1%. Mentioning frequencies for all other complications varied. CONCLUSION: Important complications are not always disclosed during the surgical informed consent process for live donor nephrectomy. Informed consent procedures vary. To optimally prepare living kidney donors for the procedure, a standardized informed consent procedure for live donor nephrectomy is highly recommended. PMID- 27260314 TI - Feasibility of laparoscopy-assisted gastrectomy for patients with poor physical status: A propensity-score matching study. AB - BACKGROUND: Laparoscopically-assisted gastrectomy (LAG) has been established to be a minimally invasive treatment for early gastric cancer. However, few studies have shown the feasibility of LAG in patients with risky comorbidities according to the American Society of Anesthesiologists physical status (ASA-PS) classification. We performed this retrospective cohort study to assess the feasibility of LG in patients with an ASA-PS class of 3 or higher. METHODS: We retrospectively identified 214 patients with an ASA-PS class of 3 or 4 among 1192 patients who underwent radical gastrectomy with lymph-node dissection between 1999 and 2014 in our hospital. Finally, 106 patients were generated by propensity score matching between LAG and open gastrectomy (OG). Postoperative complications were compared between LAG and OG. RESULT: The overall incidence of complications was the same in LAG (30%) and OG (30%). Surgical complications were similar in LAG and OG (19% and 17%, p = 0.80). Medical complications also did not differ significantly between LAG and OG (21% and 15%, p = 0.45). CONCLUSION: LAG was a feasible procedure for patients with gastric cancer who had an ASA-PS class of 3 or 4 and could undergo general anesthesia. LAG can become an optional treatment for such risky patients. PMID- 27260315 TI - Neprilysin and Natriuretic Peptide Regulation in Heart Failure. AB - Neprilysin is acknowledged as a key player in neurohormonal regulation, a cornerstone of modern drug therapy in chronic heart failure. In the cardiovascular system, neprilysin cleaves numerous vasoactive peptides, some with mainly vasodilating effects (natriuretic peptides, adrenomedullin, bradykinin) and other with mainly vasoconstrictor effects (angiotensin I and II, endothelin 1). For decades, neprilysin has been an important biotarget. Academia and industry have combined active efforts to search for neprilysin inhibitors (NEPIs) that might be useful in clinical practice. NEPI monotherapy was initially tested with little success due to efficacy issues. Next, combination of NEPI and ACE inhibiting activity agents were abandoned due to safety concerns. Recently, the combination of NEPI and ARB, also known as ARNI, has shown better than expected results in heart failure with reduced ejection fraction, and multitude of ongoing studies are set to prove its value across the heart failure spectrum. PMID- 27260316 TI - Improving the "urinary side" of acute kidney injury monitoring. PMID- 27260317 TI - Anatomy of the middle rectal artery: a review of the historical literature. AB - The middle rectal artery is a very important anatomical structure in rectal cancer surgery. It is the only vessel that penetrates through the proper rectal fascia into the pelvic cavity, and therefore threatens the integrity of total mesorectal excision. Moreover, it is very closely related to the lateral lymphatic drainage root. The definition of the middle rectal artery is ambiguous, and different frequencies, origins, and trajectories have been reported in various papers. The frequency of the middle rectal artery is reported to range from 12 to 97 %. Traditionally, the middle rectal artery is described as an artery that penetrates the pelvic plexus from the lateral side along with the lateral ligament; the frequency of this lateral type of middle rectal artery ranges from 20 to 30 %. However, the reports that describe higher frequency values also consider another type of middle rectal artery, which penetrates the neuro-vascular bundle from the antero-lateral direction; this antero-lateral type of middle rectal artery tends to be a small vessel, and frequently forms a common trunk with the prostatic artery. With advancements in endoscopic surgery, the knowledge of the precise anatomy of this structure is becoming more crucial for optimal rectal cancer surgery. PMID- 27260318 TI - Regeneration of test in testate amoebae of the genus Arcella (Tubulinea, Arcellinida). AB - Although the presence of test is the most fundamental synapomorphy of arcellinid lobose amoebae, the significance of tests in maintenance of the biological functions of these organisms is still largely unclear. This paper demonstrates the effect of the artificial test removal on the behaviour, ultrastructure and reproduction of the testate lobose amoebae belonging to the two species of the genus Arcella. The studied cells can survive after artificial removal of their test, and many specimens are capable of building a test de novo. We investigated this process and found that test-free cells of Arcella in culture remained alive for weeks; they are able to move and feed, but never undergo normal cell division accompanied by mitosis. Test-free cells can restore the test in three different ways: (1) building almost normal test; (2) building a very small single-chambered test; (3) building a test which consisted of several small chambers attached to each other. Although newly constructed tests are abnormal, cells restore shape, size and other characteristic features of the test in the next one or two generations of descendants. The results obtained suggest that the test may be critically important for completing a life cycle of an amoeba. PMID- 27260319 TI - Too much medicine in older people? Deprescribing through shared decision making. PMID- 27260320 TI - Understanding the feasibility and implications of implementing early peanut introduction for prevention of peanut allergy. AB - BACKGROUND: A recent randomized trial (the Learning Early About Peanut Allergy [LEAP] study) provided evidence that earlier dietary peanut introduction reduces peanut allergy prevalence in high-risk infants. However, questions remain as to how to identify and target the "at-risk" population to facilitate timely introduction of peanut. OBJECTIVE: We sought to use population-based infant peanut allergy data to understand feasibility and implications of implementing the LEAP trial intervention. METHODS: Using the HealthNuts study cohort (n = 5276) of 1-year-old infants, we explored the impact of using various criteria to identify infants at high risk of developing peanut allergy, and the implications of skin prick test (SPT) screening before peanut introduction. RESULTS: Screening all infants with early onset eczema and/or egg allergy could require testing 16% of the population and would still miss 23% of peanut allergy cases; 29% of screened infants would require clinical follow-up because of being SPT-positive. Around 11% of high-risk infants were excluded from the LEAP study because of an SPT wheal size of more than 4 mm to peanut at baseline; data from the HealthNuts study suggest that 80% of these would be peanut allergic on food challenge. There were no life-threatening events among either low- or high-risk infants whose parents chose to introduce peanut at home in the first year of life, or in 150 peanut-allergic infants during hospital-based challenges. CONCLUSIONS: Based on this large epidemiological study, a population program aiming to identify and screen all infants at risk of peanut allergy would pose major cost and logistic challenges that need to be carefully considered. Further research might be required to provide data for low-risk infants. PMID- 27260323 TI - Non-face-to-face treatment of stress urinary incontinence: predictors of success after 1 year. AB - INTRODUCTION AND HYPOTHESIS: The objective was to determine predictors of long term success in women with stress urinary incontinence (SUI) treated with a 3 month pelvic floor muscle training (PFMT) program delivered via the Internet or a brochure. METHODS: We included 169 women with SUI >=1 time/week who completed the 1-year follow-up (n = 169, mean age 50.3, SD 10.1 years). Three outcome variables defined success after 1 year: Patient Global Impression of Improvement (PGI-I), International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF), and sufficient treatment. Using logistic regression, we analyzed data from the baseline, and from the 4-month and 1-year follow-ups, for potential predictors of success. RESULTS: Of the participants, 77 % (129 out of 169) were successful in >=1 of the outcomes, 23 % (37 out of 160) were successful in all 3. Participants with successful short-term results were more likely to succeed in the corresponding outcome at 1 year than those without successful short-term results (adjusted odds ratios [ORs]: PGI 5.15, 95 % confidence interval [CI] 2.40-11.03), ICIQ-UI SF 6.85 (95 % CI 2.83-16.58), and sufficient treatment 3.78 (95 % CI 1.58-9.08). Increasing age predicted success in PGI-I and sufficient treatment (adjusted OR 1.06, 95 % CI 1.02-1.10, and 1.08, 95 % CI, 1.03-1.13 respectively). Compared with not training regularly, regular PFMT at 1 year predicted success for PGI and sufficient treatment (adjusted OR 2.32, 95 % CI 1.04-5.20, and 2.99, 95 % CI 1.23-7.27 respectively). CONCLUSION: The long-term success of a non-face-to-face treatment program for SUI with a focus on PFMT can be predicted by successful short-term results, increasing age, and the performance of regular PFMT after 1 year. PMID- 27260322 TI - Curcumin slows osteoarthritis progression and relieves osteoarthritis-associated pain symptoms in a post-traumatic osteoarthritis mouse model. AB - BACKGROUND: Curcumin has been shown to have chondroprotective potential in vitro. However, its effect on disease and symptom modification in osteoarthritis (OA) is largely unknown. This study aimed to determine whether curcumin could slow progression of OA and relieve OA-related pain in a mouse model of destabilization of the medial meniscus (DMM). METHODS: Expression of selected cartilage degradative-associated genes was evaluated in human primary chondrocytes treated with curcumin and curcumin nanoparticles and assayed by real-time PCR. The mice subjected to DMM surgery were orally administered curcumin or topically administered curcumin nanoparticles for 8 weeks. Cartilage integrity was evaluated by Safranin O staining and Osteoarthritis Research Society International (OARSI) score, and by immunohistochemical staining of cleaved aggrecan and type II collagen, and levels of matrix metalloproteinase (MMP)-13 and ADAMTS5. Synovitis and subchondral bone thickness were scored based on histologic images. OA-associated pain and symptoms were evaluated by von Frey assay, and locomotor behavior including distance traveled and rearing. RESULTS: Both curcumin and nanoparticles encapsulating curcumin suppressed mRNA expression of pro-inflammatory mediators IL-1beta and TNF-alpha, MMPs 1, 3, and 13, and aggrecanase ADAMTS5, and upregulated the chondroprotective transcriptional regulator CITED2, in primary cultured chondrocytes in the absence or presence of IL-1beta. Oral administration of curcumin significantly reduced OA disease progression, but showed no significant effect on OA pain relief. Curcumin was detected in the infrapatellar fat pad (IPFP) following topical administration of curcumin nanoparticles on the skin of the injured mouse knee. Compared to vehicle treated controls, topical treatment led to: (1) reduced proteoglycan loss and cartilage erosion and lower OARSI scores, (2) reduced synovitis and subchondral plate thickness, (3) reduced immunochemical staining of type II collagen and aggrecan cleavage epitopes and numbers of chondrocytes positive for MMP-13 and ADAMTS5 in the articular cartilage, and (4) reduced expression of adipokines and pro-inflammatory mediators in the IPFP. In contrast to oral curcumin, topical application of curcumin nanoparticles relieved OA-related pain as indicated by reduced tactile hypersensitivity and improved locomotor behavior. CONCLUSION: This study provides the first evidence that curcumin significantly slows OA disease progression and exerts a palliative effect in an OA mouse model. PMID- 27260324 TI - Which factors should be considered in choosing pessary type and size for pelvic organ prolapse patients in a fitting trial? AB - INTRODUCTION AND HYPOTHESIS: This study explored whether the optimal pessary type and size can be predicted using the specific pelvic organ prolapse quantification system (POP-Q) measurements in women with pelvic organ prolapse in a fitting trial. METHODS: We conducted a prospective study in women who had undergone pessary fitting. A total of 78 patients with stage II, III or IV symptomatic pelvic organ prolapse completed a detailed history. Data were analysed using nonparametric tests, continuity correction chi-squared tests and multivariate logistic regression. RESULTS: Differences in total vaginal length (TVL; p < 0.01) and vaginal introitus width/TVL ratio (p = 0.012) were observed between patients with and without a history of hysterectomy. Patients with a history of hysterectomy and patients with a larger vaginal introitus had more success with the Gellhorn pessary than with the ring pessary with support (p = 0.005 and p = 0.01, respectively). Factors determining the size of the ring pessary with support were the genital hiatus (GH) width (p = 0.044), TVL (p = 0.011), vaginal introitus width (p < 0.001), and vaginal introitus width/TVL ratio (p = 0.025). Factors determining the size of the Gellhorn pessary were the GH width (p = 0.025), GH width/TVL ratio (p = 0.013), vaginal introitus width (p = 0.003), vaginal introitus width/TVL ratio (p = 0.001), stage of apical prolapse (p = 0.006) and stage of posterior prolapse (p = 0.003). CONCLUSIONS: Patients with a history of hysterectomy or with a larger vaginal introitus were more likely to achieve success with the Gellhorn pessary. The GH width and the vaginal introitus width influenced the size of both pessaries chosen. The TVL was predictive of the optimal size of the ring pessary with support but was not predictive of the optimal size of the Gellhorn pessary. Finally, the size of the Gellhorn pessary was associated with POP stage. PMID- 27260325 TI - Differential control of dopamine ascending pathways by serotonin2B receptor antagonists: New opportunities for the treatment of schizophrenia. AB - Recent studies suggest that the central serotonin2B receptor (5-HT2BR) could be an interesting pharmacological target for treating neuropsychiatric disorders related to dopamine (DA) dysfunction, such as schizophrenia. Thus, the present study was aimed at characterizing the role of 5-HT2BRs in the control of ascending DA pathway activity. Using neurochemical, electrophysiological and behavioral approaches, we assessed the effects of two selective 5-HT2BR antagonists, RS 127445 and LY 266097, on in vivo DA outflow in DA-innervated regions, on mesencephalic DA neuronal firing, as well as in behavioral tests predictive of antipsychotic efficacy and tolerability, such as phencyclidine (PCP)-induced deficit in novel object recognition (NOR) test, PCP-induced hyperlocomotion and catalepsy. Both RS 127445 (0.16 mg/kg, i.p.) and LY 266097 (0.63 mg/kg, i.p.) increased DA outflow in the medial prefrontal cortex (mPFC). RS 127445, devoid of effect in the striatum, decreased DA outflow in the nucleus accumbens, and potentiated haloperidol (0.1 mg/kg, s.c.)-induced increase in mPFC DA outflow. Also, RS 127445 decreased the firing rate of DA neurons in the ventral tegmental area, but had no effect in the substantia nigra pars compacta. Finally, both RS 127445 and LY 266097 reversed PCP-induced deficit in NOR test, and reduced PCP-induced hyperlocomotion, without inducing catalepsy. These results demonstrate that 5-HT2BRs exert a differential control on DA pathway activity, and suggest that 5-HT2BR antagonists could represent a new class of drugs for improved treatment of schizophrenia, with an ideal profile of effects expected to alleviate cognitive and positive symptoms, without eliciting extrapyramidal symptoms. PMID- 27260326 TI - Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats. AB - Repeated local administration of ethanol (EtOH) sensitized the posterior ventral tegmental area (pVTA) to the local dopamine (DA)-stimulating effects of EtOH. Chronic alcohol drinking increased nucleus accumbens (NAC) DA transmission and pVTA glutamate transmission in alcohol-preferring (P) rats. The objectives of the present study were to determine the effects of chronic alcohol drinking by P rats on the (a) sensitivity and response of the pVTA DA neurons to the DA-stimulating actions of EtOH, and (b) negative feedback control of DA (via D2 auto-receptors) and glutamate (via group II mGlu auto-receptors) release in the pVTA. EtOH (50 or 150 mg%) or the D2/3 receptor antagonist sulpiride (100 or 200 MUM) was microinjected into the pVTA while DA was sampled with microdialysis in the NAC shell (NACsh). The mGluR2/3 antagonist LY341495 (1 or 10 MUM) was perfused through the pVTA via reverse microdialysis and local extracellular glutamate and DA levels were measured. EtOH produced a more robust increase of NACsh DA in the 'EtOH' than 'Water' groups (e.g., 150 mg% EtOH: to ~ 210 vs 150% of baseline). In contrast, sulpiride increased DA release in the NACsh more in the 'Water' than 'EtOH' groups (e.g., 200 MUM sulpiride: to ~ 190-240 vs 150-160% of baseline). LY341495 (at 10 MUM) increased extracellular glutamate and DA levels in the 'Water' (to ~ 150-180% and 180-230% of baseline, respectively) but not the 'EtOH' groups. These results indicate that alcohol drinking enhanced the DA-stimulating effects of EtOH, and attenuated the functional activities of D2 auto-receptors and group II mGluRs within the pVTA. PMID- 27260327 TI - Recombinant Ralstonia eutropha engineered to utilize xylose and its use for the production of poly(3-hydroxybutyrate) from sunflower stalk hydrolysate solution. AB - BACKGROUND: Lignocellulosic raw materials have extensively been examined for the production of bio-based fuels, chemicals, and polymers using microbial platforms. Since xylose is one of the major components of the hydrolyzed lignocelluloses, it is being considered a promising substrate in lignocelluloses based fermentation process. Ralstonia eutropha, one of the most powerful and natural producers of polyhydroxyalkanoates (PHAs), has extensively been examined for the production of bio-based chemicals, fuels, and polymers. However, to the best of our knowledge, lignocellulosic feedstock has not been employed for R. eutropha probably due to its narrow spectrum of substrate utilization. Thus, R. eutropha engineered to utilize xylose should be useful in the development of microbial process for bio based products from lignocellulosic feedstock. RESULTS: Recombinant R. eutropha NCIMB11599 expressing the E. coli xylAB genes encoding xylose isomerase and xylulokinase respectively, was constructed and examined for the synthesis of poly(3-hydroxybutyrate) [P(3HB)] using xylose as a sole carbon source. It could produce 2.31 g/L of P(3HB) with a P(3HB) content of 30.95 wt% when it was cultured in a nitrogen limited chemically defined medium containing 20.18 g/L of xylose in a batch fermentation. Also, recombinant R. eutropha NCIMB11599 expressing the E. coli xylAB genes produced 5.71 g/L of P(3HB) with a P(3HB) content of 78.11 wt% from a mixture of 10.05 g/L of glucose and 10.91 g/L of xylose in the same culture condition. The P(3HB) concentration and content could be increased to 8.79 g/L and 88.69 wt%, respectively, when it was cultured in the medium containing 16.74 g/L of glucose and 6.15 g/L of xylose. Further examination of recombinant R. eutropha NCIMB11599 expressing the E. coli xylAB genes by fed-batch fermentation resulted in the production of 33.70 g/L of P(3HB) in 108 h with a P(3HB) content of 79.02 wt%. The concentration of xylose could be maintained as high as 6 g/L, which is similar to the initial concentration of xylose during the fed-batch fermentation suggesting that xylose consumption is not inhibited during fermentation. Finally, recombinant R. eutorpha NCIMB11599 expressing the E. coli xylAB gene was examined for the production of P(3HB) from the hydrolysate solution of sunflower stalk. The hydrolysate solution of sunflower stalk was prepared as a model lignocellulosic biomass, which contains 78.8 g/L of glucose, 26.9 g/L of xylose, and small amount of 4.8 g/L of galactose and mannose. When recombinant R. eutropha NCIMB11599 expressing the E. coli xylAB genes was cultured in a nitrogen limited chemically defined medium containing 23.1 g/L of hydrolysate solution of sunflower stalk, which corresponds to 16.8 g/L of glucose and 5.9 g/L of xylose, it completely consumed glucose and xylose in the sunflower stalk based medium resulting in the production of 7.86 g/L of P(3HB) with a P(3HB) content of 72.53 wt%. CONCLUSIONS: Ralstonia eutropha was successfully engineered to utilize xylose as a sole carbon source as well as to co-utilize it in the presence of glucose for the synthesis of P(3HB). In addition, R. eutropha engineered to utilized xylose could synthesize P(3HB) from the sunflower stalk hydrolysate solution containing glucose and xylose as major sugars, which suggests that xylose utilizing R. eutropha developed in this study should be useful for development of lignocellulose based microbial processes. PMID- 27260321 TI - MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis. AB - The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials. PMID- 27260328 TI - Dysexecutive syndrome in amnesic mild cognitive impairment: a multicenter study. AB - BACKGROUND: Executive functions (EF) in Alzheimer's disease (AD), classically related to the prefrontal cortex, have been forgotten in mild stages, given more importance to temporal lobe associated disorders, such as memory. The study of disexecutive syndrome (DS) has been relegated to advanced stages of the disease. Our goal is to demonstrate that EF are already present in amnesic mild cognitive impairment (aMCI). Furthermore, we are interested in knowing whether poor scores in EF tests are related to the progression to AD or another kind of dementia. METHODS: We studied patients with aMCI (n = 81) and healthy controls (n = 142) from neurological departments of several centers of Basque Country with a cross sectional design. Patients underwent a complete neuropsychological evaluation, neuroimaging testing APOE genotype and 3 year of prospective follow-up. RESULTS: In the first visit, patients with aMCI showed more alterations in tests that evaluate EF such as Stroop, trail-making and categorical verbal fluency. More alterations were also found in NPI scale (P <0.05). Stroop and Trail-Making test were not associated with the future development of AD, but fluency (p = 0.01) and apathy (p = 0.031) did. No patient developed a different kind of dementia different from AD. CONCLUSIONS: DS is a broad concept not confined to frontal lobes, and can be found in early stages of aMCI. DS impacts negatively on patient autonomy and may have prognostic value. PMID- 27260329 TI - Non-surgical management of rectal cancer. Series of 68 cases, long follow up in two leading centres in Argentina. AB - BACKGROUND: The non-surgical management in a selected group of rectal cancer patients has shown promising results with adequate follow up. AIMS: describing the results of the non-surgical management in patients with complete clinical response, with a close follow up. METHODS: Between 2006 and 2015, patients with rectal cancer, stages I-III, without metastasis, treated with neoadjuvant CRT/CT, who had clinical complete response were included. CCR was defined through digital palpation, endoscopy-based criteria and MRI. Follow up was set according to institutional guidelines. RESULTS: 68 patients were included. Initial stage was assessed with MRI in 55/68 pts and EUS 11/68. Considering the recurrence risk factors 57.6% (29/68) were T2-3ab N0, 3.3% (2/68) were T4N0, 29% (20/68) were T3 4 N1-2, with 39.7% with positive MRC. Mean distance to the anal margin was 3cm. Chemoradiation included radiotherapy at 50.4cGy, and concurrent capecitabine. In 22% a fluoropirimidine and oxaliplatin-based schema was used as induction therapy. Median follow up was 37.5 months and response assessment time 9 weeks (5 19). Eleven patients recurred, 6 endoluminally, 3 developed mesorectal recurrence, and two distant failure. Five years DFS and OS were 76.3% and 93.8%. CONCLUSIONS: conservative management was feasible with close follow up in leading cancer centres. In this series, DFS and OS were comparable to the data already reported in the literature. PMID- 27260330 TI - Early decrease of liver stiffness after initiation of antiviral therapy in patients with chronic hepatitis C. PMID- 27260331 TI - Autoimmune pancreatitis and inflammatory bowel disease: Case series and review of the literature. AB - BACKGROUND: An association between autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) has been documented, but its clinical significance remains unclear. AIMS: Characterize the particular phenotypes of IBD and AIP in patients with both diseases (IBD-AIP). METHODS: Retrospective study of patients with IBD AIP followed at our IBD referral centre and literature search to identify previous reports of IBD-AIP patients. RESULTS: We found 5 cases of IBD-AIP in our records and 5 prior studies reporting 47 additional IBD-AIP patients. A combined analysis showed that most IBD-AIP patients were young males with ulcerative colitis, usually extensive, and that in all Crohn's disease cases, the colon was involved. IBD severity was heterogeneous across studies, ranging from mild disease to severe disease requiring colectomy. The most frequent type of AIP was idiopathic duct-centric pancreatitis (type 2) and it most often occurred after the diagnosis of IBD. AIP presentation and treatment were similar to those in the general population. CONCLUSIONS: AIP occurs rarely with IBD; in the other way around, up to 1/3 of AIP patients, especially type 2, may have concomitant IBD. IBD-AIP patients are usually males presenting extensive colitis. More data are needed on the impact of AIP, if any, in IBD course. PMID- 27260332 TI - Colorectal cancer care in elderly patients: Unsolved issues. AB - Colorectal cancers are common in elderly patients. However, cancer screening is poorly used after 75. Elderly patients form a heterogeneous population with specific characteristics. Standards of care cannot therefore be transposed from young to elderly patients. Tumour resection is frequently performed but adjuvant chemotherapy is rarely prescribed as there are no clearly established standards of care. In a metastatic setting, recent phase III studies have demonstrated that doublet front-line chemotherapy provided no survival benefit. Moreover, several studies have established the benefit of bevacizumab in association with chemotherapy. There is a lack of evidence for the efficacy of anti-epidermal growth factor antibodies in elderly patients. Geriatric assessments could help to select the adequate treatment strategy for individual patients. Geriatric oncology is now the challenge we have to face, and more specific trials are needed. PMID- 27260333 TI - Sperm Morphology Assessment in Captive Neotropical Primates. AB - The main objective of this study was to evaluate sperm morphology in four neotropical primate species to compare the sperm morphological traits and the sperm morphometric parameters as a basis for establishing normative sperm standards for each species. Data from 80 ejaculates collected from four primate species, Callithrix jacchus, Callimico goeldii, Alouatta caraya and Ateles geoffroyi, were analysed for detection of sperm morphological alterations using subjective World Health Organization (WHO-2010) standards and Sperm Deformity Index (SDI) criteria, objective computer-assisted sperm morphometry analysis (CASMA) and subpopulation sperm determination (SSD) methods. There were multiple differences (p < 0.01) observed among primate species in values obtained from WHO 2010, SDI, CASMA and SSD sperm analysis methods. In addition, multiple significant positive and negative correlations were observed between the sperm morphological traits (SDI, Sperm Deformity Index Head Defects, Sperm Deformity Index Midpiece Defects, Sperm Deformity Index Tail Defects, Normal Sperm, Head Defects, Midpiece Defects and Tail Defects) and the sperm morphometric parameters (SSD, Area (A), Perimeter (P), Length (L), Width (W), Ellipticity, Elongation and Rugosity) (p <= 0.046). In conclusion, our findings using different evaluation methods indicate that pronounced sperm morphological variation exists among these four neotropical primate species. Because of the strong relationship observed among morphological and morphometric parameters, these results suggest that application of objective analysis methods could substantially improve the reliability of comparative studies and help to establish valid normative sperm values for neotropical primates. PMID- 27260334 TI - Dermatology consultations significantly contribute quality to care of hospitalized patients: a prospective study of dermatology inpatient consults at a tertiary care center. AB - BACKGROUND: Cutaneous abnormalities are common in hospitalized patients but are frequently missed or misdiagnosed by admitting teams. Inpatient dermatology consultations provide important information to help diagnose and manage these patients. However, few studies have analyzed dermatology inpatient consultations and their effect. METHODS: We prospectively collected information for 691 consecutive dermatology consultations from November 2013 to November 2014. RESULTS: Patients ranged in age from newborns to 97 years old. The internal medicine service requested the most consultations (45%). Only 6.5% of consultations were requested within 24 hours of appearance of cutaneous findings. Before consultation, 70.3% of patients did not receive treatment for or based on their cutaneous findings. Dermatology consultation resulted in treatment change in 81.9% of patients. The most common diagnoses were drug rash and contact dermatitis. Biopsies confirmed 71.7% of the initial bedside diagnoses by the dermatology consultation team. CONCLUSIONS: Common skin diseases were responsible for the majority of dermatology consultations. Most patients were not treated for their cutaneous conditions before the dermatology consultation. Dermatology consultations resulted in treatment changes in the majority of cases. PMID- 27260335 TI - Venetoclax: First Global Approval. AB - Venetoclax (VenclextaTM) is an oral selective inhibitor of the prosurvival protein BCL-2 and therefore restores the apoptotic ability of malignant cells. The drug arose from research by Abbott Laboratories (now AbbVie) during a collaboration with Genentech and is being co-developed by AbbVie and Genentech/Roche primarily for the treatment of haematological malignancies. Venetoclax is approved in the USA for use as monotherapy in patients with chronic lymphocytic leukaemia (CLL) with the 17p deletion (as detected by an approved FDA test) who have received at least one prior therapy, and is awaiting approval for similar indications in the EU and Canada. Venetoclax is also in phase I-III development as combination therapy for CLL, phase I/II development as monotherapy and/or combination therapy for non-Hodgkin lymphomas (including diffuse large B cell lymphoma, mantle cell lymphoma, follicular lymphoma) and acute myeloid leukaemia, and phase I development for multiple myeloma, systemic lupus erythematosus and breast cancer. This article summarizes the milestones in the development of venetoclax leading to this first approval for CLL. PMID- 27260336 TI - Impact of Statin Therapy on Plasma Uric Acid Concentrations: A Systematic Review and Meta-Analysis. AB - PURPOSE: The aim of this study was to ascertain the effect size of statins in modulating plasma uric acid concentrations. DATA SOURCES: A search was undertaken of the MEDLINE, SCOPUS, Web of Science and Google Scholar electronic databases. STUDY SELECTION: Studies meeting the following criteria were included: (i) randomized controlled trials with either a parallel or crossover design; (ii) investigated the impact of statin therapy on plasma uric acid concentrations; and (iii) presentation of sufficient information on uric acid values at baseline and at the end of follow-up in each group, or presenting the net change. DATA SYNTHESIS: The present meta-analysis suggested a significant reduction in plasma uric acid levels following statin therapy; however, this does not seem to be a class effect as subgroup analysis revealed a significant reduction with atorvastatin and simvastatin only, and not with pravastatin and rosuvastatin. CONCLUSIONS: Atorvastatin and simvastatin, but not the other statins, can reduce serum uric acid levels. PMID- 27260338 TI - 46,XX ovotesticular DSD associated with a SOX3 gene duplication in a SRY-negative boy. PMID- 27260339 TI - Pseudoalteromonas neustonica sp. nov., isolated from the sea surface microlayer of the Ross Sea (Antarctica), and emended description of the genus Pseudoalteromonas. AB - A Gram-stain-negative, facultatively anaerobic, rod-shaped and motile strain, designated PAMC 28425T, was isolated from a sea surface microlayer sample from the Ross Sea, Antarctica. Analysis of the 16S rRNA gene sequence of strain PAMC 28425T showed an affiliation with the genus Pseudoalteromonas. Phylogenetic analyses revealed that strain PAMC 28425T formed a clade with Pseudoalteromonas prydzensis MB8-11T and Pseudoalteromonas mariniglutinosaKMM 3635T with 16S rRNA gene sequence similarities of 98.3-98.6 %. Genomic relatedness analyses based on the average nucleotide identity and the genome-to-genome distance showed that strain PAMC 28425T is clearly distinguished from the phylogenetically close relatives. Cells of strain PAMC 28425T grew optimally at 25 degrees C and pH 7.5 8.5 in the presence of 1.0-3.0 % (w/v) sea salts. The major cellular fatty acids (>10 %) were C16 : 1omega6c and/or C16 : 1omega7c, C16 : 0, and C18 : 1omega6c and/or C18 : 1omega7c. The genomic DNA G+C content was 39.7 mol%. On the basis of the phylogenetic, genomic, chemotaxonomic and phenotypic data presented, we propose the name Pseudoalteromonas neustonica sp. nov. with the type strain PAMC 28425T (=KCCM 43187T=JCM 31286T). PMID- 27260337 TI - Discrimination of amygdala response predicts future separation anxiety in youth with early deprivation. AB - BACKGROUND: Significant disruption in caregiving is associated with increased internalizing symptoms, most notably heightened separation anxiety symptoms during childhood. It is also associated with altered functional development of the amygdala, a neurobiological correlate of anxious behavior. However, much less is known about how functional alterations of amygdala predict individual differences in anxiety. Here, we probed amygdala function following institutional caregiving using very subtle social-affective stimuli (trustworthy and untrustworthy faces), which typically result in large differences in amygdala signal, and change in separation anxiety behaviors over a 2-year period. We hypothesized that the degree of differentiation of amygdala signal to trustworthy versus untrustworthy face stimuli would predict separation anxiety symptoms. METHODS: Seventy-four youths mean (SD) age = 9.7 years (2.64) with and without previous institutional care, who were all living in families at the time of testing, participated in an fMRI task designed to examine differential amygdala response to trustworthy versus untrustworthy faces. Parents reported on their children's separation anxiety symptoms at the time of scan and again 2 years later. RESULTS: Previous institutional care was associated with diminished amygdala signal differences and behavioral differences to the contrast of untrustworthy and trustworthy faces. Diminished differentiation of these stimuli types predicted more severe separation anxiety symptoms 2 years later. Older age at adoption was associated with diminished differentiation of amygdala responses. CONCLUSIONS: A history of institutional care is associated with reduced differential amygdala responses to social-affective cues of trustworthiness that are typically exhibited by comparison samples. Individual differences in the degree of amygdala differential responding to these cues predict the severity of separation anxiety symptoms over a 2-year period. These findings provide a biological mechanism to explain the associations between early caregiving adversity and individual differences in internalizing symptomology during development, thereby contributing to individualized predictions of future clinical outcomes. PMID- 27260340 TI - Benchmarking pediatric cranial CT protocols using a dose tracking software system: a multicenter study. AB - OBJECTIVES: To benchmark regional standard practice for paediatric cranial CT procedures in terms of radiation dose and acquisition parameters. METHODS: Paediatric cranial CT-data were retrospectively collected during a 1-year period, in 3 different hospitals of the same country. A dose tracking system was used to automatically gather information. Dose (CTDI and DLP), scan length, amount of retakes and demographic data were stratified by age and clinical indication; appropriate use of child-specific protocols was assessed. RESULTS: In total, 296 paediatric cranial CT-procedures were collected. Although the median dose of each hospital was below national and international diagnostic reference level (DRL) for all age categories, statistically significant (p-value < 0.001) dose differences among hospitals were observed. The hospital with lowest dose levels showed smallest dose variability and used age-stratified protocols for standardizing paediatric head exams. Erroneous selection of adult protocols for children still occurred, mostly in the oldest age-group. CONCLUSION: Even though all hospitals complied with national and international DRLs, dose tracking and benchmarking showed that further dose optimization and standardization is possible by using age-stratified protocols for paediatric cranial CT. Moreover, having a dose tracking system revealed that adult protocols are still applied for paediatric CT, a practice that must be avoided. KEY POINTS: * Significant differences were observed in the delivered dose between age-groups and hospitals. * Using age-adapted scanning protocols gives a nearly linear dose increase. * Sharing dose-data can be a trigger for hospitals to reduce dose levels. PMID- 27260341 TI - Does the high-intensity zone (HIZ) of lumbar Intervertebral discs always represent an annular fissure? AB - OBJECTIVES: The aim of this study was to examine high-intensity zone (HIZ) characteristics on both T1- and T2-weighted sagittal magnetic resonance (MR) images, and to reveal their exact nature. MATERIALS: Seventy-three patients with low back pain and HIZs (identified on T2-weighted images) were included. Patients, aged 25-80 years (mean 51), were divided into two groups: the 'single HIZ' group exhibited HIZs only on T2-weighted images, while the 'dual-HIZ' group exhibited HIZs on both T2-weighted and T1-weighted images. Tissue corresponding to the HIZ was harvested from surgery for analysis. RESULTS: Eighty-two discs were studied, from 39 patients with single HIZs, 30 with dual HIZs, and four with both in the posterior annulus. HIZ volume, volume ratio, and signal intensity on T2-weighted images from the dual-HIZ group were significantly greater. Surgery was able to successfully restore patients' ability in both groups, while conservative treatments were less effective for patients with dual HIZs. Histology revealed outer annular fissures invaded by granulation tissue in the single-HIZ group. In dual-HIZ discs, Von Kossa staining and CT scans showed more calcified or ossified lesions (94.1 vs. 0 %, P<0.001), and chemical analysis showed significantly higher calcium content. CONCLUSIONS: HIZs on both T2- and T1 weighted images represent calcified tissue, possibly from a vertebral endplate. A new concept of dual HIZ should be defined. KEY POINTS: * Conventional definition of an HIZ refers to T2-weighted images only. * Dual HIZs have greater HIZ volume, volume ratio, and signal intensity. * HIZs on both T2- and T1-weighted images represent calcified tissue. * Conservative treatments are less likely to be effective for patients with dual HIZs. PMID- 27260343 TI - A novel regression model from RGB image data to spectroradiometric correlates optimized for tooth colored shades. AB - OBJECTIVES: Objectives of this study were to correlate RGB data from the VITA Linearguide 3D Master and VITA Bleached Guide 3D Master shade guides with their spectroradiometric correlates through a regression model while indicating a methodology for validation of accuracy of digital imaging systems. Additional objectives were to provide summary RGB data and to determine a relationship between lightness and RGB values for these shade guides. METHODS: Radiant energy measurements and images were taken with a Canon Rebel T3i and Macro Ring Lite MR 14EX for each shade tab. RGB data was extracted using Image J and compared with spectroradiometric measurements. Regression models relating the RGB data to spectroradiometric counterparts in CIE XYZ and absolute reflectance were developed using SAS 9.3. Image data was statistically analyzed to determine a relationship between RGB values and lightness. RESULTS: Regression models with R(2) values greater than 0.99 for RGB to XYZ and greater than 0.95 for RGB to absolute reflectance were developed. Summary RGB data for the shade guides including Pearson correlation coefficients ranging between -0.92 and -0.97 for RGB related to lightness was determined. CONCLUSIONS: A relationship between RGB and lightness for the shade guides was found. Regression models were developed that allow tooth color information to be translated from digital images to accurate shade tab correlates for color matching purposes in dentistry. This allows for optimal color accuracy when using digital imaging to translate color information and provides a method of validating digital imaging systems for color accuracy. PMID- 27260342 TI - Fine-needle aspiration versus core needle biopsy for diagnosis of thyroid malignancy and neoplasm: a matched cohort study. AB - OBJECTIVES: To compare the diagnostic performances of fine-needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of thyroid malignancy and neoplasm in patients who underwent surgery for thyroid nodules. METHODS: This retrospective study was approved by the institutional review board, and the need to obtain informed consent was waived. 3192 patients who underwent FNA (n = 3048) or CNB (n = 144) for diagnosis of thyroid nodules and then proceeded with surgery were included. Surgical pathologic diagnosis was the reference standard. Diagnostic performances of FNA and CNB to predict malignancy and neoplasm were compared. Propensity score matching was used to match patients with FNA with those with CNB because there were significant differences in the number of nodules and nodule characteristics between the FNA and CNB groups. RESULTS: Before matching, the sensitivity and accuracy of FNA were significantly higher or comparable with those of CNB, and the specificity, negative predictive value and positive predictive value were comparable. After matching, the diagnostic performances were similar, with the exception of specificity for predicting neoplasm being higher with CNB than with FNA. CONCLUSION: FNA showed comparable diagnostic performance to CNB; therefore, there may be no benefit in performing CNB to diagnose papillary thyroid carcinoma and neoplasm. KEY POINTS: * Diagnostic performances of FNA and CNB for thyroid malignancy and neoplasm were compared. * FNA showed comparable performances to CNB both before and after statistical matching. * There may be no benefit in performing CNB, given the comparable performances. PMID- 27260344 TI - [Mycetoma and their treatment]. AB - Mycetoma are chronic subcutaneous infections, endemic in dry tropical regions. It can be caused either by actinomycetes or by fungi, presenting as filamentous grains in vivo. The foot is the most common localization. The main complication is osseous involvement. Patients are rural workers living in areas situated far from medical centers. Too often, they reach well-equipped hospitals with advanced mutilating lesions. Early case detection is the first condition for good therapeutic results. Clinical presentations of actinomycetoma and eumycetoma are similar, only biological diagnosis can distinguish the two etiological forms. This distinction is essential as medical therapy for each is radically different. Precise identification of the causal agent is required for targeted treatment but it can only be realized in rare specialized laboratories. For actinomycetoma, standard therapy is trimethoprim-sulphamethoxazole (STX). Duration of treatment period is one-year minimum. In case of poor response to STX or high risk of dissemination, a combination with amikacin gave high cure rate. Other options as amoxicillin-clavulanate are available. Medical cure of actinomycetoma is generally obtained with antibiotic treatments and surgical indications are exceptional. Disappointing results were observed using antifungal in the treatment of eumycetoma and medical therapy must be completed with surgical excision. Itraconazole is now the most used drug, new triazoles are on evaluation. PMID- 27260345 TI - Evidence-Based Program Service Deserts: A Geographic Information Systems (GIS) Approach to Identifying Service Gaps for State-Level Implementation Planning. AB - The long term effects of untreated mental health need for individuals, families and society has prompted a number of federal policy statements encouraging the use of evidence-based programs (EBP) in children's healthcare. However, among other challenges of evidence-based practice implementation, states often do not know where to make investments based on population need. In this paper we present the use of a Geographic Information System approach to undertake a mental health needs assessment for Washington State. Our study found that this technology can be beneficially applied to conducting needs assessment for EBP implementation, and we provide recommendations for future applications. PMID- 27260346 TI - Estimation of identification limit for a small-type OSL dosimeter on the medical images by measurement of X-ray spectra. AB - Our aim in this study is to derive an identification limit on a dosimeter for not disturbing a medical image when patients wear a small-type optically stimulated luminescence (OSL) dosimeter on their bodies during X-ray diagnostic imaging. For evaluation of the detection limit based on an analysis of X-ray spectra, we propose a new quantitative identification method. We performed experiments for which we used diagnostic X-ray equipment, a soft-tissue-equivalent phantom (1-20 cm), and a CdTe X-ray spectrometer assuming one pixel of the X-ray imaging detector. Then, with the following two experimental settings, corresponding X-ray spectra were measured with 40-120 kVp and 0.5-1000 mAs at a source-to-detector distance of 100 cm: (1) X-rays penetrating a soft-tissue-equivalent phantom with the OSL dosimeter attached directly on the phantom, and (2) X-rays penetrating only the soft-tissue-equivalent phantom. Next, the energy fluence and errors in the fluence were calculated from the spectra. When the energy fluence with errors concerning these two experimental conditions was estimated to be indistinctive, we defined the condition as the OSL dosimeter not being identified on the X-ray image. Based on our analysis, we determined the identification limit of the dosimeter. We then compared our results with those for the general irradiation conditions used in clinics. We found that the OSL dosimeter could not be identified under the irradiation conditions of abdominal and chest radiography, namely, one can apply the OSL dosimeter to measurement of the exposure dose in the irradiation field of X-rays without disturbing medical images. PMID- 27260347 TI - Verification of the dose attenuation of a newly developed vacuum cushion for intensity-modulated radiation therapy of prostate cancer. AB - This study measured the dose attenuation of a newly developed vacuum cushion for intensity-modulated radiation therapy (IMRT) of prostate cancer, and verified the effect of dose-correction accuracy in a radiation treatment planning system (RTPS). The new cushion was filled with polystyrene foams inflated 15-fold (Sphi ? 1 mm) to reduce contraction caused by air suction and was compared to normal polystyrene foam inflated to 50-fold (Sphi ? 2 mm). The dose attenuation at several thicknesses of compression bag filled with normal and low-inflation materials was measured using an ionization chamber; and then the calculated RTPS dose was compared to ionization chamber measurements, while the new cushion was virtually included as region of interest in the calculation area. The dose attenuation rate of the normal cushion was 0.010 %/mm (R (2) = 0.9958), compared to 0.031 %/mm (R (2) = 0.9960) in the new cushion. Although the dose attenuation rate of the new cushion was three times that of the normal cushion, the high agreement between calculated dose by RTPS and ionization chamber measurements was within approximately 0.005 %/mm. Thus, the results of the current study indicate that the new cushion may be effective in clinical use for dose calculation accuracy in RTPS. PMID- 27260348 TI - Greek health professionals' perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information. AB - BACKGROUND: Every year in Europe 60,000 women develop cervical cancer and 30,000 die from the disease. HPV vaccines are currently believed to constitute an important element of cervical cancer control strategy. Currently in Greece, the HPV vaccine is given on demand after prescription by a healthcare professional. Health care professionals' role is key as they are in a position to discuss HPV vaccination with parents, adolescents and young women. This study is aiming to explore health care professionals' perceptions of the HPV vaccine, state policy recommendations and their own role with regards to communication of relevant health information. METHODS: This was an in-depth, qualitative study, employing a stratified, purposeful sampling. Fifteen face-to-face, semi-structured interviews were conducted with health care professionals from a variety of disciplines: pediatrics, obstetrics and gynecology, infectious diseases, pharmacy, dermatology, general practice. Thematic qualitative analysis was used to analyze participants' accounts. RESULTS: Five major themes were identified: health care professionals' perceptions towards the HPV vaccine (recognition of importance, concerns about safety, effectiveness and impact of long-term use), animosity between medical specialties (territorial disputes among professional bodies, role advocacy, role limitations), health care professionals' perceptions of the public's attitudes (effects of cultural beliefs, health professionals' attitudes, media and family), the role of the state (health policy issues, lack of guidance, unmet expectations) and their own role (provision of health information, sex education). CONCLUSIONS: Health professionals' concerns, lack of role definition and uniform information provision have led to territorial disputes among professional bodies and distrust among different medical specialties. Positive and negative judgements deriving from a multitude of sources have resulted in the confusion of the general public, as manifested by low vaccination rates. Due to the lack of clear regulation of vaccination prescription, administration and mode of delivery, factors such as lack of knowledge, cultural beliefs and personal attitudes have shaped the vaccination landscape. These factors have neither been explored nor addressed prior to the initiation of this public health effort and as such there is an evident less than efficient use of resources. PMID- 27260349 TI - Focused cardiopulmonary ultrasound for assessment of dyspnea in a resource limited setting. AB - BACKGROUND: The diagnosis and management of acutely dyspneic patients in resource limited developing world settings poses a particular challenge. Focused cardiopulmonary ultrasound (CPUS) may assist in the emergency diagnosis and management of patients with acute dyspnea by identifying left ventricular systolic dysfunction, pericardial effusion, interstitial pulmonary edema, and pleural effusion. We sought to assess the accuracy of emergency providers performing CPUS after a training intervention in a limited-resource setting; a secondary objective was to assess the ability of CPUS to affect change of clinician diagnostic assessment and acute management in patients presenting with undifferentiated dyspnea. METHODS AND RESULTS: After a training intervention for Haitian emergency providers, patients with dyspnea presenting urgently to a regional referral center in Haiti underwent a rapid CPUS examination by the treating physician. One hundred seventeen patients (median age of 36 years, 56 % female) were prospectively evaluated with a standardized CPUS exam. Blinded expert review of ultrasound images was performed by two board certified cardiologists and one ultrasound fellowship trained emergency physician. Inter observer agreement was determined using an agreement coefficient (kappa). Sensitivity and Specificity with confidence intervals were calculated. Pre-test and post-test clinician impressions and management plans were compared to assess for a change. We enrolled 117 patients with undifferentiated dyspnea. Upon expert image review, prevalence of left ventricular systolic dysfunction was 40.2 %, and in those with systolic dysfunction, the average EF was 14 % (+/-9 %). The parasternal long axis (PLAX) single view was predictive of an overall abnormal echo with PPV of abnormal PLAX 95 % and NPV 93 % of normal PLAX. Weighted kappa for pericardial effusion between the Haitian physicians and two cardiology reviewers was 0.81 (95 % CI 0.75-0.87, p value <0.001) and for ejection fraction was 0.98 (95 % CI 0.98-0.99, p value <0.001). For lung ultrasound, a kappa statistic assessing agreement between the Haitian physician and the EP for pleural effusion was 0.73, and for interstitial syndrome was 0.49. Detailed test characteristics are detailed in Table 3. Overall, there was a change in treating clinician impression in 15.4 % (95 % CI 9-22 %) and change in management in 19.6 % (95 % CI 12-27 %) of patients following CPUS. A significant structural heart disease was common: 48 % of patients were noted to have abnormal right ventricular systolic function, 36 % had at least moderate mitral regurgitation, and 7.7 % had a moderate to large pericardial effusion. CONCLUSIONS: A focused training intervention in CPUS was sufficient for providers in a limited-resource setting to accurately identify left ventricular systolic dysfunction, pericardial effusion, evidence of interstitial syndrome, and pleural effusions in dyspneic patients. Clinicians were able to integrate CPUS into their clinical impressions and management plans and reported a high level of confidence in their ultrasound findings. PMID- 27260350 TI - Influence of demographic and tumour variables on prostate cancer treatment with curative intent in Spain. Results of the 2010 national prostate cancer registry. AB - OBJECTIVE: The aim of this study is to determine which cancer and demographic criteria influence the indication for surgery (radical prostatectomy) or radiation therapy (external or brachytherapy) in the treatment of prostate cancer. MATERIAL AND METHODS: An analysis of the 2714 patients of the 2010 National Prostate Cancer Registry treated with curative intent. The analysed variables were age, prostate-specific antigen (PSA), prostate volume, the number of biopsy cores, the percentage of positive cores, the stage, Gleason score, the type of pathologist, the presence of perineural invasion and the study centre. We analysed the association among these variables and the type of treatment (surgery vs. radiation therapy/brachytherapy), using a univariate analysis (Student's t test and chi-squared) and a binary multiple logistic regression. RESULTS: The 48.12% of the patients (1306/2714) were treated with surgery, and 51.88% (1,408/2,714) underwent radiation therapy/brachytherapy. Differences were observed between the patients treated with prostatectomy and those treated with radiation therapy/brachytherapy (p<.05) in age (63.50+/-6.5 vs. 69.0+/-6.7), PSA (8.76+/-16.97 vs. 13.21+/-15.88), biopsied cores, percentage of positives cores (30.0+/-22 vs. 38.7+/-29), Gleason score (G6: 53.9% vs. 46.1%; G7: 45% vs. 55% G8 10: 26.6%, 73.4%), stage (localised: 50% vs. 50%; locally advanced: 14.6% vs. 85.4%), perineural invasion and hospital centre. In the multivariate analysis, the selected independent variables were age, PSA, percentage of positives cores, stage, Gleason score and hospital centre. CONCLUSION: According to our study, age, tumour aggressiveness and stage and the centre where the patient will be treated affect the selection of curative treatment for prostate cancer. PMID- 27260351 TI - Corrigendum to "Differential involvement of glutamatergic and catecholaminergic activity within the amygdala during taste aversion retrieval on memory expression and updating" [Behav. Brain Res. 307 (2016) 120-125]. PMID- 27260352 TI - Society of Skeletal Radiology 39th Annual Meeting March 13-16, 2016. PMID- 27260353 TI - Screening of the TBK1 gene in familial and sporadic amyotrophic lateral sclerosis patients of Chinese origin. AB - TANK-binding kinase 1 (TBK1) has been recently identified as a risk gene of amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the contribution of TBK1 mutations to Chinese ALS patients. We sequenced the coding regions of TBK1 in a cohort of Chinese ALS patients, including 271 sporadic ALS patients and 23 familial ALS patients. Two potentially pathogenic mutations, L62P and I334T, were identified in two independent sporadic ALS patients, accounting for 0.7% of total ALS cases. Both mutations were absent from our 384 healthy controls and public single nucleotide polymorphisms databases. In conclusion, we propose that TBK1 is not a frequent causal gene in Chinese ALS patients. PMID- 27260354 TI - Periplasmic Cytophaga hutchinsonii Endoglucanases Are Required for Use of Crystalline Cellulose as the Sole Source of Carbon and Energy. AB - The soil bacterium Cytophaga hutchinsonii actively digests crystalline cellulose by a poorly understood mechanism. Genome analyses identified nine genes predicted to encode endoglucanases with roles in this process. No predicted cellobiohydrolases, which are usually involved in the utilization of crystalline cellulose, were identified. Chromosomal deletions were performed in eight of the endoglucanase-encoding genes: cel5A, cel5B, cel5C, cel9A, cel9B, cel9C, cel9E, and cel9F Each mutant retained the ability to digest crystalline cellulose, although the deletion of cel9C caused a modest decrease in cellulose utilization. Strains with multiple deletions were constructed to identify the critical cellulases. Cells of a mutant lacking both cel5B and cel9C were completely deficient in growth on cellulose. Cell fractionation and biochemical analyses indicate that Cel5B and Cel9C are periplasmic nonprocessive endoglucanases. The requirement of periplasmic endoglucanases for cellulose utilization suggests that cellodextrins are transported across the outer membrane during this process. Bioinformatic analyses predict that Cel5A, Cel9A, Cel9B, Cel9D, and Cel9E are secreted across the outer membrane by the type IX secretion system, which has been linked to cellulose utilization. These secreted endoglucanases may perform the initial digestion within amorphous regions on the cellulose fibers, releasing oligomers that are transported into the periplasm for further digestion by Cel5B and Cel9C. The results suggest that both cell surface and periplasmic endoglucanases are required for the growth of C. hutchinsonii on cellulose and that novel cell surface proteins may solubilize and transport cellodextrins across the outer membrane. IMPORTANCE: The bacterium Cytophaga hutchinsonii digests crystalline cellulose by an unknown mechanism. It lacks processive cellobiohydrolases that are often involved in cellulose digestion. Critical cellulolytic enzymes were identified by genetic analyses. Intracellular (periplasmic) nonprocessive endoglucanases performed an important role in cellulose utilization. The results suggest a model involving partial digestion at the cell surface, solubilization and uptake of cellodextrins across the outer membrane by an unknown mechanism, and further digestion within the periplasm. The ability to sequester cellodextrins and digest them intracellularly may limit losses of soluble cellobiose to other organisms. C. hutchinsonii uses an unusual approach to digest cellulose and is a potential source of novel proteins to increase the efficiency of conversion of cellulose into soluble sugars and biofuels. PMID- 27260355 TI - Effects of Carbohydrate Source on Genetic Competence in Streptococcus mutans. AB - The capacity to internalize and catabolize carbohydrates is essential for dental caries pathogens to persist and cause disease. The expression of many virulence related attributes by Streptococcus mutans, an organism strongly associated with human dental caries, is influenced by the peptide signaling pathways that control genetic competence. Here, we demonstrate a relationship between the efficiency of competence signaling and carbohydrate source. A significant increase in the activity of the promoters for comX, comS, and comYA after exposure to competence stimulating peptide (CSP) was observed in cells growing on fructose, maltose, sucrose, or trehalose as the primary carbohydrate source, compared to cells growing on glucose. However, only cells grown in the presence of trehalose or sucrose displayed a significant increase in transformation frequency. Notably, even low concentrations of these carbohydrates in the presence of excess glucose could enhance the expression of comX, encoding a sigma factor needed for competence, and the effects on competence were dependent on the cognate sugar:phosphotransferase permease for each carbohydrate. Using green fluorescent protein (GFP) reporter fusions, we observed that growth in fructose or trehalose resulted in a greater proportion of the population activating expression of comX and comS, encoding the precursor of comX-inducing peptide (XIP), after addition of CSP, than growth in glucose. Thus, the source of carbohydrate significantly impacts the stochastic behaviors that regulate subpopulation responses to CSP, which can induce competence in S. mutans IMPORTANCE: The signaling pathways that regulate development of genetic competence in Streptococcus mutans are intimately intertwined with the pathogenic potential of the organism, impacting biofilm formation, stress tolerance, and expression of known virulence determinants. Induction of the gene for the master regulator of competence, ComX, by competence stimulating peptide (CSP) occurs in a subpopulation of cells. Here, we show that certain carbohydrates that are common in the human diet enhance the ability of CSP to activate transcription of comX and that a subset of these carbohydrates stimulates progression to the competent state. The cognate sugar:phosphotransferase permeases for each sugar are needed for these effects. Interestingly, single-cell analysis shows that the carbohydrates that increase com gene expression do so by enhancing the proportion of cells that respond to CSP. A mathematical model is developed to explain how carbohydrates modulate bistable behavior in the system via the ComRS pathway and ComX stability. PMID- 27260356 TI - Influence of Host Ecology and Behavior on Campylobacter jejuni Prevalence and Environmental Contamination Risk in a Synanthropic Wild Bird Species. AB - Campylobacter jejuni is a foodborne pathogen that often leads to human infections through the consumption of contaminated poultry. Wild birds may play a role in the transmission of C. jejuni by acting as reservoir hosts. Despite ample evidence that wild birds harbor C. jejuni, few studies have addressed the role of host ecology in transmission to domestic animals or humans. We tested the hypothesis that host social behavior and habitat play a major role in driving transmission risk. C. jejuni infection and host ecology were studied simultaneously in wild American crows (Corvus brachyrhynchos) in Davis, CA, over 3 years. We found that 178 of 337 samples tested were culture positive (53%), with infection varying by season and host age. Among adult crows, infection rates were highest during the winter, when migrants return and crows form large communal roosts. Nestlings had the highest risk of infection, and whole-genome sequencing supports the observation of direct transmission between nestlings. We deployed global positioning system (GPS) receivers to quantify habitat use by crows; space use was nonrandom, with crows preferentially occupying some habitats while avoiding others. This behavior drastically amplified the risk of environmental contamination from feces in specific locations. This study demonstrates that social behavior contributes to infection within species and that habitat use leads to a heterogeneous risk of cross-species transmission. IMPORTANCE: Campylobacter jejuni is the most common cause of gastroenteritis in industrialized countries. Despite efforts to reduce the colonization of poultry flocks and eventual infection of humans, the incidence of human C. jejuni infection has remained high. Because wild birds can harbor strains of C. jejuni that eventually infect humans, there has long been speculation that wild birds might act as an important reservoir in the C. jejuni infection cycle. We simultaneously studied infection prevalence, social behavior, and movement ecology in wild American crows (Corvus brachyrhynchos). We found that social behavior contributed to patterns of infection and that movement behavior resulted in some areas having a high risk of transmission while others had a low risk. The incorporation of ecological data into studies of C. jejuni in wild birds has the potential to resolve when and how wild birds contribute to domestic animal and human C. jejuni infection, leading to better control of initial poultry contamination. PMID- 27260357 TI - Phylogenetically Structured Differences in rRNA Gene Sequence Variation among Species of Arbuscular Mycorrhizal Fungi and Their Implications for Sequence Clustering. AB - Arbuscular mycorrhizal (AM) fungi form mutualisms with plant roots that increase plant growth and shape plant communities. Each AM fungal cell contains a large amount of genetic diversity, but it is unclear if this diversity varies across evolutionary lineages. We found that sequence variation in the nuclear large subunit (LSU) rRNA gene from 29 isolates representing 21 AM fungal species generally assorted into genus- and species-level clades, with the exception of species of the genera Claroideoglomus and Entrophospora However, there were significant differences in the levels of sequence variation across the phylogeny and between genera, indicating that it is an evolutionarily constrained trait in AM fungi. These consistent patterns of sequence variation across both phylogenetic and taxonomic groups pose challenges to interpreting operational taxonomic units (OTUs) as approximations of species-level groups of AM fungi. We demonstrate that the OTUs produced by five sequence clustering methods using 97% or equivalent sequence similarity thresholds failed to match the expected species of AM fungi, although OTUs from AbundantOTU, CD-HIT-OTU, and CROP corresponded better to species than did OTUs from mothur or UPARSE. This lack of OTU-to species correspondence resulted both from sequences of one species being split into multiple OTUs and from sequences of multiple species being lumped into the same OTU. The OTU richness therefore will not reliably correspond to the AM fungal species richness in environmental samples. Conservatively, this error can overestimate species richness by 4-fold or underestimate richness by one-half, and the direction of this error will depend on the genera represented in the sample. IMPORTANCE: Arbuscular mycorrhizal (AM) fungi form important mutualisms with the roots of most plant species. Individual AM fungi are genetically diverse, but it is unclear whether the level of this diversity differs among evolutionary lineages. We found that the amount of sequence variation in an rRNA gene that is commonly used to identify AM fungal species varied significantly between evolutionary groups that correspond to different genera, with the exception of two genera that are genetically indistinguishable from each other. When we clustered groups of similar sequences into operational taxonomic units (OTUs) using five different clustering methods, these patterns of sequence variation caused the number of OTUs to either over- or underestimate the actual number of AM fungal species, depending on the genus. Our results indicate that OTU-based inferences about AM fungal species composition from environmental sequences can be improved if they take these taxonomically structured patterns of sequence variation into account. PMID- 27260358 TI - Ammonia as an In Situ Sanitizer: Influence of Virus Genome Type on Inactivation. AB - Treatment of human excreta and animal manure (HEAM) is key in controlling the spread of persistent enteric pathogens, such as viruses. The extent of virus inactivation during HEAM storage and treatment appears to vary with virus genome type, although the reasons for this variability are not clear. Here, we investigated the inactivation of viruses of different genome types under conditions representative of HEAM storage or mesophilic digestion. The goals were to characterize the influence of HEAM solution conditions on inactivation and to determine the potential mechanisms involved. Specifically, eight viruses representing the four viral genome types (single-stranded RNA [ssRNA], double stranded RNA [dsRNA], single-stranded DNA [ssDNA], and double-stranded DNA [dsDNA]) were exposed to synthetic solutions with well-controlled temperature (20 to 35 degrees C), pH (8 to 9), and ammonia (NH3) concentrations (0 to 40 mmol liter(-1)). DNA and dsRNA viruses were considerably more resistant than ssRNA viruses, resulting in up to 1,000-fold-longer treatment times to reach a 4-log inactivation. The apparently slower inactivation of DNA viruses was rationalized by the higher stability of DNA than that of ssRNA in HEAM. Pushing the system toward harsher pH (>9) and temperature (>35 degrees C) conditions, such as those encountered in thermophilic digestion and alkaline treatments, led to more consistent inactivation kinetics among ssRNA and other viruses. This suggests that the dependence of inactivation on genome type disappeared in favor of protein-mediated inactivation mechanisms common to all viruses. Finally, we recommend the use of MS2 as a conservative indicator to assess the inactivation of ssRNA viruses and the stable PhiX174 or dsDNA phages as indicators for persistent viruses. IMPORTANCE: Viruses are among the most environmentally persistent pathogens. They can be present in high concentrations in human excreta and animal manure (HEAM). Therefore, appropriate treatment of HEAM is important prior to its reuse or discharge into the environment. Here, we investigated the factors that determine the persistence of viruses in HEAM, and we determined the main mechanisms that lead to their inactivation. Unlike other organisms, viruses can have four different genome types (double- or single-stranded RNA or DNA), and the viruses studied herein represent all four types. Genome type appeared to be the major determinant for persistence. Single-stranded RNA viruses are the most labile, because this genome type is susceptible to degradation in HEAM. In contrast, the other genome types are more stable; therefore, inactivation is slower and mainly driven by the degradation of viral proteins. Overall, this study allows us to better understand the behavior of viruses in HEAM. PMID- 27260359 TI - Microbial Transformations of Selenium Species of Relevance to Bioremediation. AB - Selenium species, particularly the oxyanions selenite (SeO3 (2-)) and selenate (SeO4 (2-)), are significant pollutants in the environment that leach from rocks and are released by anthropogenic activities. Selenium is also an essential micronutrient for organisms across the tree of life, including microorganisms and human beings, particularly because of its presence in the 21st genetically encoded amino acid, selenocysteine. Environmental microorganisms are known to be capable of a range of transformations of selenium species, including reduction, methylation, oxidation, and demethylation. Assimilatory reduction of selenium species is necessary for the synthesis of selenoproteins. Dissimilatory reduction of selenate is known to support the anaerobic respiration of a number of microorganisms, and the dissimilatory reduction of soluble selenate and selenite to nanoparticulate elemental selenium greatly reduces the toxicity and bioavailability of selenium and has a major role in bioremediation and potentially in the production of selenium nanospheres for technological applications. Also, microbial methylation after reduction of Se oxyanions is another potentially effective detoxification process if limitations with low reaction rates and capture of the volatile methylated selenium species can be overcome. This review discusses microbial transformations of different forms of Se in an environmental context, with special emphasis on bioremediation of Se pollution. PMID- 27260360 TI - A Modular, Tn7-Based System for Making Bioluminescent or Fluorescent Salmonella and Escherichia coli Strains. AB - Our goal was to develop a robust tagging method that can be used to track bacterial strains in vivo To address this challenge, we adapted two existing systems: a modular plasmid-based reporter system (pCS26) that has been used for high-throughput gene expression studies in Salmonella and Escherichia coli and Tn7 transposition. We generated kanamycin- and chloramphenicol-resistant versions of pCS26 with bacterial luciferase, green fluorescent protein (GFP), and mCherry reporters under the control of sigma(70)-dependent promoters to provide three different levels of constitutive expression. We improved upon the existing Tn7 system by modifying the delivery vector to accept pCS26 constructs and moving the transposase genes from a nonreplicating helper plasmid into a temperature sensitive plasmid that can be conditionally maintained. This resulted in a 10- to 30-fold boost in transposase gene expression and transposition efficiencies of 10(-8) to 10(-10) in Salmonella enterica serovar Typhimurium and E. coli APEC O1, whereas the existing Tn7 system yielded no successful transposition events. The new reporter strains displayed reproducible signaling in microwell plate assays, confocal microscopy, and in vivo animal infections. We have combined two flexible and complementary tools that can be used for a multitude of molecular biology applications within the Enterobacteriaceae This system can accommodate new promoter-reporter combinations as they become available and can help to bridge the gap between modern, high-throughput technologies and classical molecular genetics. IMPORTANCE: This article describes a flexible and efficient system for tagging bacterial strains. Using our modular plasmid system, a researcher can easily change the reporter type or the promoter driving expression and test the parameters of these new constructs in vitro Selected constructs can then be stably integrated into the chromosomes of desired strains in two simple steps. We demonstrate the use of this system in Salmonella and E. coli, and we predict that it will be widely applicable to other bacterial strains within the Enterobacteriaceae This technology will allow for improved in vivo analysis of bacterial pathogens. PMID- 27260361 TI - Development of a CRISPR-Cas9 Tool Kit for Comprehensive Engineering of Bacillus subtilis. AB - The establishment of a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system for strain construction in Bacillus subtilis is essential for its progression toward industrial utility. Here we outline the development of a CRISPR-Cas9 tool kit for comprehensive genetic engineering in B. subtilis In addition to site-specific mutation and gene insertion, our approach enables continuous genome editing and multiplexing and is extended to CRISPR interference (CRISPRi) for transcriptional modulation. Our tool kit employs chromosomal expression of Cas9 and chromosomal transcription of guide RNAs (gRNAs) using a gRNA transcription cassette and counterselectable gRNA delivery vectors. Our design obviates the need for multicopy plasmids, which can be unstable and impede cell viability. Efficiencies of up to 100% and 85% were obtained for single and double gene mutations, respectively. Also, a 2.9-kb hyaluronic acid (HA) biosynthetic operon was chromosomally inserted with an efficiency of 69%. Furthermore, repression of a heterologous reporter gene was achieved, demonstrating the versatility of the tool kit. The performance of our tool kit is comparable with those of systems developed for Escherichia coli and Saccharomyces cerevisiae, which rely on replicating vectors to implement CRISPR-Cas9 machinery. IMPORTANCE: In this paper, as the first approach, we report implementation of the CRISPR-Cas9 system in Bacillus subtilis, which is recognized as a valuable host system for biomanufacturing. The study enables comprehensive engineering of B. subtilis strains with virtually any desired genotypes/phenotypes and biochemical properties for extensive industrial application. PMID- 27260362 TI - Quantifying Variability in Growth and Thermal Inactivation Kinetics of Lactobacillus plantarum. AB - The presence and growth of spoilage organisms in food might affect the shelf life. In this study, the effects of experimental, reproduction, and strain variabilities were quantified with respect to growth and thermal inactivation using 20 Lactobacillus plantarum strains. Also, the effect of growth history on thermal resistance was quantified. The strain variability in MUmax was similar (P > 0.05) to reproduction variability as a function of pH, aw, and temperature, while being around half of the reproduction variability (P < 0.05) as a function of undissociated lactic acid concentration [HLa]. The cardinal growth parameters were estimated for the L. plantarum strains, and the pHmin was between 3.2 and 3.5, the aw,min was between 0.936 and 0.953, the [HLamax], at pH 4.5, was between 29 and 38 mM, and the Tmin was between 3.4 and 8.3 degrees C. The average D values ranged from 0.80 min to 19 min at 55 degrees C, 0.22 to 3.9 min at 58 degrees C, 3.1 to 45 s at 60 degrees C, and 1.8 to 19 s at 63 degrees C. In contrast to growth, the strain variability in thermal resistance was on average six times higher than the reproduction variability and more than ten times higher than the experimental variability. The strain variability was also 1.8 times higher (P < 0.05) than the effect of growth history. The combined effects of strain variability and growth history on D value explained all of the variability as found in the literature, although with bias. Based on an illustrative milk processing chain, strain variability caused ~2-log10 differences in growth between the most and least robust strains and >10-log10 differences after thermal treatment. IMPORTANCE: Accurate control and realistic prediction of shelf life is complicated by the natural diversity among microbial strains, and limited information on microbiological variability is available for spoilage microorganisms. Therefore, the objectives of the present study were to quantify strain variability, reproduction (biological) variability, and experimental variability with respect to the growth and thermal inactivation kinetics of Lactobacillus plantarum and to quantify the variability in thermal resistance attributed to growth history. The quantitative knowledge obtained on experimental, reproduction, and strain variabilities can be used to improve experimental designs and to adequately select strains for challenge growth and inactivation tests. Moreover, the integration of strain variability in prediction of microbial growth and inactivation kinetics will result in more realistic predictions of L. plantarum dynamics along the food production chain. PMID- 27260363 TI - Novel Feruloyl Esterase from Lactobacillus fermentum NRRL B-1932 and Analysis of the Recombinant Enzyme Produced in Escherichia coli. AB - A total of 33 Lactobacillus strains were screened for feruloyl esterase (FE) activity using agar plates containing ethyl ferulate as the sole carbon source, and Lactobacillus fermentum NRRL B-1932 demonstrated the strongest FE activity among a dozen species showing a clearing zone on the opaque plate containing ethyl ferulate. FE activities were monitored using high-performance liquid chromatography with an acetonitrile-trifluoroacetic acid gradient. To produce sufficient purified FE from L. fermentum strain NRRL B-1932 (LfFE), the cDNA encoding LfFE (Lffae) was amplified and cloned by using available closely related genome sequences and overexpressed in Escherichia coli A 29.6-kDa LfFE protein was detected from the protein extract of E. coli BL21(pLysS) carrying pET28bLffae upon IPTG (isopropyl-beta-d-thiogalactopyranoside) induction. The recombinant LfFE containing a polyhistidine tag was purified by nickel-nitrilotriacetic acid affinity resin. The purified LfFE showed strong activities against several artificial substrates, including p-nitrophenyl acetate and 4-methylumbelliferyl p trimethylammoniocinnamate chloride. The optimum pH and temperature of the recombinant LfFE were around 6.5 and 37 degrees C, respectively, as determined using either crude or purified recombinant LfFE. This study will be essential for the production of the LfFE in E. coli on a larger scale that could not be readily achieved by L. fermentum fermentation. IMPORTANCE: The production of feruloyl esterase (FE) from Lactobacillus fermentum NRRL B-1932 reported in this study will have immense potential commercial applications not only in biofuel production but also in pharmaceutical, polymer, oleo chemical, cosmetic additive, and detergent industries, as well as human health-related applications, including food flavoring, functional foods, probiotic agents, preventive medicine, and animal feed. Given the essential role FE plays in the production of hydroxycinnamic acids and ferulic acid, plus the generally regarded as safe status of lactobacilli, which therefore have less regulatory concerns, LfFE from the probiotic L. fermentum reported in this work can be directly used for increased production of high-value hydroxycinnamates and ferulic acid from natural or synthetic carbon sources. PMID- 27260364 TI - Biochemical Characteristics and Substrate Degradation Pattern of a Novel Exo-Type beta-Agarase from the Polysaccharide-Degrading Marine Bacterium Flammeovirga sp. Strain MY04. AB - Exo-type agarases release disaccharide units (3,6-anhydro-l-galactopyranose-alpha 1,3-d-galactose) from the agarose chain and, in combination with endo-type agarases, play important roles in the processive degradation of agarose. Several exo-agarases have been identified. However, their substrate-degrading patterns and corresponding mechanisms are still unclear because of a lack of proper technologies for sugar chain analysis. Herein, we report the novel properties of AgaO, a disaccharide-producing agarase identified from the genus Flammeovirga AgaO is a 705-amino-acid protein that is unique to strain MY04. It shares sequence identities of less than 40% with reported GH50 beta-agarases. Recombinant AgaO (rAgaO) yields disaccharides as the sole final product when degrading agarose and associated oligosaccharides. Its smallest substrate is a neoagarotetraose, and its disaccharide/agarose conversion ratio is 0.5. Using fluorescence labeling and two-stage mass spectrometry analysis, we demonstrate that the disaccharide products are neoagarobiose products instead of agarobiose products, as verified by (13)C nuclear magnetic resonance spectrum analysis. Therefore, we provide a useful oligosaccharide sequencing method to determine the patterns of enzyme cleavage of glycosidic bonds. Moreover, AgaO produces neoagarobiose products by gradually cleaving the units from the nonreducing end of fluorescently labeled sugar chains, and so our method represents a novel biochemical visualization of the exolytic pattern of an agarase. Various truncated AgaO proteins lost their disaccharide-producing capabilities, indicating a strict structure-function relationship for the whole enzyme. This study provides insights into the novel catalytic mechanism and enzymatic properties of an exo-type beta-agarase for the benefit of potential future applications. IMPORTANCE: Exo-type agarases can degrade agarose to yield disaccharides almost exclusively, and therefore, they are important tools for disaccharide preparation. However, their enzymatic mechanisms and agarose degradation patterns are still unclear due to the lack of proper technologies for sugar chain analysis. In this study, AgaO was identified as an exo-type agarase of agarose-degrading Flammeovirga bacteria, representing a novel branch of glycoside hydrolase family 50. Using fluorescence labeling, high-performance liquid chromatography, and mass spectrum analysis technologies, we provide a useful oligosaccharide sequencing method to determine the patterns of enzyme cleavage of glycosidic bonds. We also demonstrate that AgaO produces neoagarobiose by gradually cleaving disaccharides from the nonreducing end of fluorescently labeled sugars. This study will benefit future enzyme applications and oligosaccharide studies. PMID- 27260365 TI - Heterologous Production and Characterization of Two Glyoxal Oxidases from Pycnoporus cinnabarinus. AB - The genome of the white rot fungus Pycnoporus cinnabarinus includes a large number of genes encoding enzymes implicated in lignin degradation. Among these, three genes are predicted to encode glyoxal oxidase, an enzyme previously isolated from Phanerochaete chrysosporium The glyoxal oxidase of P. chrysosporium is physiologically coupled to lignin-oxidizing peroxidases via generation of extracellular H2O2 and utilizes an array of aldehydes and alpha-hydroxycarbonyls as the substrates. Two of the predicted glyoxal oxidases of P. cinnabarinus, GLOX1 (PciGLOX1) and GLOX2 (PciGLOX2), were heterologously produced in Aspergillus niger strain D15#26 (pyrG negative) and purified using immobilized metal ion affinity chromatography, yielding 59 and 5 mg of protein for PciGLOX1 and PciGLOX2, respectively. Both proteins were approximately 60 kDa in size and N glycosylated. The optimum temperature for the activity of these enzymes was 50 degrees C, and the optimum pH was 6. The enzymes retained most of their activity after incubation at 50 degrees C for 4 h. The highest relative activity and the highest catalytic efficiency of both enzymes occurred with glyoxylic acid as the substrate. The two P. cinnabarinus enzymes generally exhibited similar substrate preferences, but PciGLOX2 showed a broader substrate specificity and was significantly more active on 3-phenylpropionaldehyde. IMPORTANCE: This study addresses the poorly understood role of how fungal peroxidases obtain an in situ supply of hydrogen peroxide to enable them to oxidize a variety of organic and inorganic compounds. This cooperative activity is intrinsic in the living organism to control the amount of toxic H2O2 in its environment, thus providing a feed-on-demand scenario, and can be used biotechnologically to supply a cheap source of peroxide for the peroxidase reaction. The secretion of multiple glyoxal oxidases by filamentous fungi as part of a lignocellulolytic mechanism suggests a controlled system, especially as these enzymes utilize fungal metabolites as the substrates. Two glyoxal oxidases have been isolated and characterized to date, and the differentiation of the substrate specificity of the two enzymes produced by Pycnoporus cinnabarinus illustrates the alternative mechanisms existing in a single fungus, together with the utilization of these enzymes to prepare platform chemicals for industry. PMID- 27260366 TI - Transfusion Independency and Histological Remission in a Patient with Advanced Primary Myelofibrosis Receiving Iron-Chelation Therapy with Deferasirox. AB - BACKGROUND: Iron overload is a common problem in patients with primary myelofibrosis and anemia due to transfusion dependency. This results in organ damage and toxic effects on hematopoietic cells in the bone marrow. At present, iron chelation therapy is not recommended in patients with myeloproliferative syndromes. CASE REPORT: We describe a very interesting development in a patient with primary myelofibrosis receiving iron chelation. Transfusion independency and a nearly complete histological remission of the underlying disease occurred within a few weeks of therapy. In addition, a change in molecular genetic findings was observed. Initially a JAK2 and a U2AF1 mutation were detected in the core biopsy. During and after therapy the U2AF1 mutation progressed, whereas the JAK2 mutation could no longer be verified. CONCLUSION: The improvement in hematopoiesis might results from reduction of oxidative stress on hematopoietic progenitor cells or other unclear deferasirox-mediated effects, whereas the reason for the change in molecular genetic findings is unclear. It appears that deferasirox might have a modulating effect on JAK2-kinase mutations. However, further investigation of selective molecular suppression properties of deferasirox are warranted. PMID- 27260367 TI - The effects of accumulated muscle fatigue on the mechanomyographic waveform: implications for injury prediction. AB - PURPOSE: Muscle fatigue has been identified as a risk factor for spontaneous muscle injuries in sport. However, few studies have investigated the accumulated effects of muscle fatigue on human muscle contractile properties. This study aimed to determine whether repeated bouts of exercise inducing acute fatigue leads to longer-term fatigue-related changes in muscle contractile properties. METHODS: Maximum voluntary contraction (MVC), electromyographic (EMG) and mechanomyographic (MMG) measures were recorded in the biceps brachii of 11 participants for 13 days, before and after a maximally fatiguing exercise protocol. The exercise protocol involved participants repetitively lifting a weight (concentric contractions only) equal to 40 % MVC, until failure. RESULTS: A significant (p < 0.05) acute pre- to post-exercise decline of biceps brachii MVC and median power frequency (MPF) was observed each day, whilst no difference existed between pre-exercise MVC or MPF values on subsequent days (days 2-13). However, decreases in number of lift repetitions and in pre-exercise MMG values of muscle belly displacement, contraction velocity and half-relaxation velocity were observed through to day 13. CONCLUSIONS: Whilst MVC and MPF measures resolved by the following day's test session, MMG measures indicated an ongoing decrement in muscle performance through days 2-13 consistent with the decline in lift repetitions observed. These results suggest that MMG may be more sensitive in detecting accumulated muscle fatigue than the 'gold standard' measures of MVC/MPF. Considering that muscle fatigue leads to injury, the on-going monitoring of MMG derived contractile properties of muscles in athletes may aid in the prediction of fatigued-induced muscle injury. PMID- 27260368 TI - Association of Hyperhomocysteinemia with Stroke Recurrence after Initial Stroke. AB - BACKGROUND AND PURPOSE: Homocysteine (Hcy) is closely associated with stroke. Despite the fact that Hcy has consistently been shown to predict development of recurrent stroke, prior studies on the association of Hcy and stroke subtypes have been inconclusive. METHODS: Data from the Ege Stroke Registry were examined and 5-year follow-up data were analyzed. Multivariate survival analyses were undertaken using Cox proportional hazards models to determine the prognostic value of Hcy in different ischemic stroke subtypes. RESULTS: Of the 9522 patients with stroke, 307 (27%) with hyperhomocysteinemia (hHcy) had recurrent stroke. Univariate Cox regression model showed that hHcy group was associated with recurrent stroke (crude hazard ratio [HR] 1.16; 95% CI 1.02-1.30). But there was no such association in multivariate regression models (adjusted HR 1.11; 95% CI .97-1.26). hHcy was not associated with any ischemic stroke subtypes at 5 years. Univariate Cox regression model showed that hHcy group was associated with overall cardiovascular events (crude HR 1.44; 95% CI 1.32-1.57). However, this association no longer existed in multivariate regression models (adjusted HR 1.01; 95% CI .93-1.12). Higher plasma Hcy group was significantly associated with higher mortality compared with normal plasma Hcy group (OR 1.83; 95% CI .45 2.32). CONCLUSIONS: Our results showed that elevated Hcy is not associated independently with stroke recurrence and overall cardiovascular events in patients with ischemic stroke. There was no association between the hHcy and stroke recurrence in the stroke subtypes within 5 years. PMID- 27260369 TI - Promoting synergies between clinical medicine and public health. PMID- 27260370 TI - Uncertainty and objectivity in clinical decision making: a clinical case in emergency medicine. AB - The evidence-based practice and evidence-based medicine (EBM) movements have promoted standardization through guideline development methodologies based on systematic reviews and meta-analyses of best available research. EBM has challenged clinicians to question their reliance on practical reasoning and clinical judgement. In this paper, we argue that the protagonists of EBM position their mission as reducing uncertainty through the use of standardized methods for knowledge evaluation and use. With this drive towards uniformity, standardization and control comes a suspicion towards intuition, creativity and uncertainty as integral parts of medical practice. We question the appropriateness of attempts to standardize professional practice through a discussion of the importance of uncertainty. Greenhalgh's taxonomy of uncertainty is used to inform an analysis of the clinical reasoning occurring in a potentially life threatening emergency situation with a young patient. The case analysis is further developed by the use of the Canadian philosopher Bernard Lonergan's theory about understanding and objective knowing. According to Lonergan it is not by getting rid of or even by reducing uncertainty, but by attending systematically to it and by relating to it in a self-conscious way, that objective knowledge can be obtained. The paper concludes that uncertainty is not a regrettable and unavoidable aspect of decision making but a productive component of clinical reasoning. PMID- 27260371 TI - Factors associated with the successful removal of indwelling urinary catheters post-operatively in the fragility hip fracture patient. AB - INTRODUCTION: Patients presenting to hospital with a fragility hip fracture are routinely catheterized in the emergency department. Studies have found that the duration of catheterization is the greatest and most important risk factor for developing a urinary tract infection. Whilst there is a considerable body of evidence around correct techniques for insertion of urinary catheters, there appears to be little evidence as to the timing of their removal. AIM OF THE STUDY: To describe the current practice of indwelling catheter (IDC) removal post operatively in the fragility hip fracture patient and to identify factors associated with the successful removal of IDCs post operatively in the same cohort of patients. METHODS: This study was a retrospective cohort analysis of patients admitted to a large, tertiary hospital with an established ortho geriatric model of care. RESULTS: Aperient regime was the only factor that appeared to have a significant impact on the successful IDC removal. The patient commenced on the aperient regime was three times more likely to have an unsuccessful IDC removal than the patient on a limited or no aperient regime. CONCLUSION: This study highlights the need for redesigning care that is patient focused, evidence-based, effective and efficient. The argument that a patient's bowel is required to be emptied prior to the successful removal of an IDC appears to be false, as in this study it was not identified as a predictor of successful IDC removal. A prospective clinical trial may be the next step forward in developing a clinical guideline for the successful removal of IDCs in the fragility hip fracture patient and/or surgical patient. Nurses have a crucial role to play in contributing to evidence-based practice and are continually challenged to do so. PMID- 27260385 TI - Enhancing the role of pharmacists in the cascade of tuberculosis care. PMID- 27260384 TI - Molecular characterization and confocal laser scanning microscopic study of Pygidiopsis macrostomum (Trematoda: Heterophyidae) parasites of guppies Poecilia vivipara. AB - Pygidiopsis macrostomum and Ascocotyle (Phagicola) pindoramensis (Digenea: Heterophyidae) parasitize guppies as intermediate hosts and, respectively, fish eating mammals or birds as definitive hosts. Heterophyids have zoonotic potential, and molecular studies associated with morphological and ecological aspects have helped to clarify their taxonomy and phylogeny. Poecilia vivipara naturally parasitized by metacercariae of both species (100% prevalence) exhibit no external signs of parasitism. In this work, four new sequences of P. macrostomum (18S rDNA, 28S rDNA and ITS2 rDNA) and one new sequence of A. (P.) pindoramensis (mtDNA cox-1) are presented. Phylogeny reconstructions linked P. macrostomum to other heterophyids, but the separation of the Heterophyidae and Opisthorchiidae remains unclear. Additionally, we used indirect immunocytochemistry and the phalloidin-fluorescence techniques allied with confocal laser scanning microscopy to describe muscular and neuronal structures of P. macrostomum. A complex arrangement of muscular fibres is associated with the tegument, suckers, gut and reproductive system. Radial fibres around the ventral sucker are thick, branched and extend to the body wall. High-resolution confocal imaging revealed a typical digenean muscular arrangement and important heterophyid morphological traits. These data will support future control measures to reduce the parasitism in guppies reared in fish farming systems, especially for aquarium and experimental purposes. PMID- 27260386 TI - A functionally integrated thermoplastic microdevice for one-step solid-phase based nucleic acid purification and isothermal amplification for facile detection of foodborne pathogen. AB - In this study, we fabricate a functionally integrated monolithic thermoplastic microdevice for continuous operation of nucleic acid purification and amplification using polycarbonate (PC). A solid-phase-based purification and subsequent isothermal amplification, specifically, thermal helicase-dependent amplification (tHDA), was performed in a single operation in a valve-free manner. PC microdevice was assembled using modified thermal bonding process under relatively low temperature and pressure condition, realized by surface chemical modification of PC into hydrophilic property using amine-bearing polyethyleneimine (PEI). After the device sealing, only the microchannel parts were selectively modified to be hydrophobic, using epoxy-terminated poly(dimethylsiloxane) (PDMS) (epoxy-PDMS) on amine-coated surface for stepwise introduction of multiple reagents in a valve-free manner. Using the integrated PC microdevice, nucleic acids from genetically modified Escherichia coli (E. coli) O157:H7 were captured inside a chamber bearing amine functionality, by electrostatic interaction, and were subsequently amplified isothermally in the same chamber. Purified DNA captured inside the microchamber was detected directly inside the chamber by fluorescence measurement, and a 92-bp long EaeA gene, inserted into the E. coli O157:H7, was successfully amplified using the integrated PC microdevice in less than 90 min, paving the way for facile identification of foodborne pathogens with simple operation and reduced peripheral operations applicable for portable healthcare purposes. Biotechnol. Bioeng. 2016;113: 2614-2623. (c) 2016 Wiley Periodicals, Inc. PMID- 27260387 TI - Cellular Energetics as a Target for Tumor Cell Elimination. AB - Investigation of cancer cell metabolism has revealed variability of the metabolic profiles among different types of tumors. According to the most classical model of cancer bioenergetics, malignant cells primarily use glycolysis as the major metabolic pathway and produce large quantities of lactate with suppressed oxidative phosphorylation even in the presence of ample oxygen. This is referred to as aerobic glycolysis, or the Warburg effect. However, a growing number of recent studies provide evidence that not all cancer cells depend on glycolysis, and, moreover, oxidative phosphorylation is essential for tumorigenesis. Thus, it is necessary to consider distinctive patterns of cancer metabolism in each specific case. Chemoresistance of cancer cells is associated with decreased sensitivity to different types of antitumor agents. Stimulation of apoptosis is a major strategy for elimination of cancer cells, and therefore activation of mitochondrial functions with direct impact on mitochondria to destabilize them appears to be an important approach to the induction of cell death. Consequently, the design of combination therapies using acclaimed cytotoxic agents directed to induction of apoptosis and metabolic agents affecting cancer cell bioenergetics are prospective strategies for antineoplastic therapy. PMID- 27260388 TI - Interleukins 1 and 6 as Main Mediators of Inflammation and Cancer. AB - The idea of a potential link between cancer and inflammation was first proposed by R. Virchow in the nineteenth century. However, clear evidence regarding a key role of inflammation in oncogenesis appeared only during the last decade. Now the tumor microenvironment is commonly considered as an obligatory and significant component of almost all types of cancer, and the cells infiltrating such microenvironment are a source of inflammatory cytokines. Such cytokines play a key role in regulating inflammation during both normal immune response and developing cancer. In this review, we explore the role of two inflammatory cytokines interleukin 1 and interleukin 6 in cancer development. These cytokines have pleiotropic effects on various cell types in the tumor microenvironment, particularly being able to regulate pro-oncogenic transcription factors NF-kappaB and STAT3. For this reason, such cytokines influence key parameters of oncogenesis, increasing cell resistance to apoptosis, proliferation of cancer cells, angiogenesis, invasion and malignancy as well as the ability of tumor cells to respond to anticancer therapy. Here we summarize novel experimental data regarding mechanisms underlying the interaction between chronic inflammation and malignant neoplasms. PMID- 27260389 TI - Problems of Glioblastoma Multiforme Drug Resistance. AB - Glioblastoma multiforme (GBL) is the most common and aggressive brain neoplasm. A standard therapeutic approach for GBL involves combination therapy consisting of surgery, radiotherapy, and chemotherapy. The latter is based on temozolomide (TMZ). However, even by applying such a radical treatment strategy, the mean patient survival time is only 14.6 months. Here we review the molecular mechanisms underlying the resistance of GBL cells to TMZ including genetic and epigenetic mechanisms. Present data regarding a role for genes and proteins MGMT, IDH1/2, YB-1, MELK, MVP/LRP, MDR1 (ABCB1), and genes encoding other ABC transporters as well as Akt3 kinase in developing resistance of GBL to TMZ are discussed. Some epigenetic regulators of resistance to TMZ such as microRNA and EZH2 are reviewed. PMID- 27260390 TI - Mitochondrial Genome Structure of Photosynthetic Eukaryotes. AB - Current ideas of plant mitochondrial genome organization are presented. Data on the size and structural organization of mtDNA, gene content, and peculiarities are summarized. Special emphasis is given to characteristic features of the mitochondrial genomes of land plants and photosynthetic algae that distinguish them from the mitochondrial genomes of other eukaryotes. The data published before the end of 2014 are reviewed. PMID- 27260391 TI - Activity of Tissue Factor in Microparticles Produced in vitro by Endothelial Cells, Monocytes, Granulocytes, and Platelets. AB - Activity of tissue factor (TF) in membrane microparticles (MPs) produced in vitro by endothelial cells (ECs), monocytes, THP-1 monocytic cells, granulocytes, and platelets was investigated. ECs were isolated from human umbilical vein, and monocytes, granulocytes, and platelets - from the blood of healthy donors. ECs, monocytes, and THP-1 cells were activated by bacterial lipopolysaccharide, granulocytes - by lipopolysaccharide or phorbol myristate acetate, and platelets by SFLLRN, thrombin receptor-activating peptide. MPs were sedimented from the culture medium or supernatant of activated cells at 20,000g for 30 min. Coagulation activity of MPs was analyzed in a modified recalcification assay by assessing their effects on coagulation of donor plasma depleted of endogenous MPs (by centrifuging at 20,000g for 90 min). MPs from all cell types accelerated plasma coagulation. Antibodies blocking TF activity prolonged coagulation lag phase in the presence of MPs from ECs, monocytes, and THP-1 cells (by 2.7-, 2.0-, and 1.8-fold, respectively), but did not influence coagulation in the presence of MPs from granulocytes and platelets. In accordance with these data, TF activity measured by its ability to activate factor X was found in MPs from ECs, monocytes, and THP-1 cells, but not in MPs from granulocytes and platelets. The data obtained indicate that active TF is present in MPs produced in vitro by ECs, monocytes, and THP-1 cells, but not in MPs derived from granulocytes and platelets. PMID- 27260392 TI - Structure, Chaperone Activity, and Aggregation of Wild-Type and R12C Mutant alphaB-Crystallins in the Presence of Thermal Stress and Calcium Ion - Implications for Role of Calcium in Cataract Pathogenesis. AB - The current study was performed with the aim to evaluate the chaperoning ability, structural features, and aggregation propensity of wild-type and R12C mutant alphaB-crystallins (alphaB-Cry) under thermal stress and in the presence of calcium ion. The results of different spectroscopic analyses suggest that wild type and mutant alphaB-Cry have dissimilar secondary and tertiary structures. Moreover, alphaB-Cry indicates slightly improved chaperone activity upon the R12C mutation. Thermal stress and calcium, respectively, enhance and reduce the extent of solvent-exposed hydrophobic surfaces accompanying formation of ordered and non ordered aggregate entities in both proteins. Compared to the wild-type protein, the R12C mutant counterpart shows significant resistance against thermal and calcium-induced aggregation. In addition, in the presence of calcium, significant structural variation was accompanied by reduction in the solvent-exposed hydrophobic patches and attenuation of chaperone activity in both proteins. Additionally, gel mobility shift assay indicates the intrinsic propensity of R12C mutant alphaB-Cry for disulfide bridge-mediated protein dimerization. Overall, the results of this study are of high significance for understanding the molecular details of different factors that are involved in the pathomechanism of cataract disorders. PMID- 27260393 TI - Interaction between Fibrinogen and Insulin-Like Growth Factor-Binding Protein-1 in Human Plasma under Physiological Conditions. AB - Fibrinogen is a plasma glycoprotein and one of the principle participants in blood coagulation. It interacts with many proteins during formation of a blood clot, including insulin-like growth factors (IGFs) and their binding proteins (IGFBP). Fibrinogen complexes were found as minor fractions in fibrinogen preparations independently of the coagulation process, and their presence influences the kinetics of polymerization. The idea of this work was to investigate whether fibrinogen in human plasma interacts with IGFBPs independently of the tissue injury or coagulation process. The results have shown that fibrinogen forms complexes with IGFBP-1 under physiological conditions. Several experimental approaches have confirmed that complexes are co-isolated with fibrinogen from plasma, they are relatively stable, and they appear as a general feature of human plasma. Several other experiments excluded the possibility that alpha-2 macroglobulin/IGFBP-1 complexes or IGFBP-1 oligomers contributed to IGFBP-1 immunoreactivity. The role of fibrinogen/IGFBP-1 complexes is still unknown. Further investigation in individuals expressing both impaired glucose control and coagulopathy could contribute to identification and understanding of their possible physiological role. PMID- 27260394 TI - Plant DNA Methyltransferase Genes: Multiplicity, Expression, Methylation Patterns. AB - Expression and methylation patterns of genes encoding DNA methyltransferases and their functionally related proteins were studied in organs of Arabidopsis thaliana plants. Genes coding for the major maintenance-type DNA methyltransferases, MET1 and CMT3, and the major de novo-type DNA methyltransferase, DRM2, are actively expressed in all organs. Similar constitutively active expression was observed for genes encoding their functionally related proteins, a histone H3K9 methyltransferase KYP and a catalytically non-active protein DRM3. Expression of the MET1 and CMT3 genes is significantly lower in developing endosperm compared with embryo. Vice versa, expression of the MET2a, MET2b, MET3, and CMT2 genes in endosperm is much more active compared with embryo. A special maintenance DNA methylation system seems to operate in endosperm. The DNMT2 and N6AMT genes encoding putative methyltransferases are constitutively expressed at low levels. CMT1 and DRM1 genes are expressed rather weakly in all investigated organs. Most of the studied genes have methylation patterns conforming to the "body-methylated gene" prototype. A peculiar feature of the MET family genes is methylation at all three possible site types (CG, CHG, and CHH). The most weakly expressed among genes of their respective families, CMT1 and DRM1, are practically unmethylated. The MET3 and N6AMT genes have unusual methylation patterns, promoter region, and most of the gene body devoid of any methylation, and the 3'-end proximal part of the gene body is highly methylated. PMID- 27260395 TI - Express Sequence Tag Analysis - Identification of Anseriformes Trypsin Genes from Full-Length cDNA Library of the Duck (Anas platyrhynchos) and Characterization of Their Structure and Function. AB - Trypsins are key proteins important in animal protein digestion by breaking down the peptide bonds on the carboxyl side of lysine and arginine residues, hence it has been used widely in various biotechnological processes. In the current study, a full-length cDNA library with capacity of 5.10(5) CFU/ml from the duck (Anas platyrhynchos) was constructed. Using express sequence tag (EST) sequencing, genes coding two trypsins were identified and two full-length trypsin cDNAs were then obtained by rapid-amplification of cDNA end (RACE)-PCR. Using Blast, they were classified into the trypsin I and II subfamilies, but both encoded a signal peptide, an activation peptide, and a 223-a.a. mature protein located in the C terminus. The two deduced mature proteins were designated as trypsin-IAP and trypsin-IIAP, and their theoretical isoelectric points (pI) and molecular weights (MW) were 7.99/23466.4 Da and 4.65/24066.0 Da, respectively. Molecular characterizations of genes were further performed by detailed bioinformatics analysis. Phylogenetic analysis revealed that trypsin-IIAP has an evolution pattern distinct from trypsin-IAP, suggesting its evolutionary advantage. Then the duck trypsin-IIAP was expressed in an Escherichia coli system, and its kinetic parameters were measured. The three dimensional structures of trypsin-IAP and trypsin-IIAP were predicted by homology modeling, and the conserved residues required for functionality were identified. Two loops controlling the specificity of the trypsin and the substrate-binding pocket represented in the model are almost identical in primary sequences and backbone tertiary structures of the trypsin families. PMID- 27260396 TI - Role of Endonuclease G in Exogenous DNA Stability in HeLa Cells. AB - Endonuclease G (EndoG) is a well-conserved mitochondrial-nuclear nuclease with dual lethal and vital roles in the cell. The aim of our study was to examine whether EndoG exerts its nuclease activity on exogenous DNA substrates such as plasmid DNA (pDNA), considering their importance in gene therapy applications. The effects of EndoG knockdown on pDNA stability and levels of encoded reporter gene expression were evaluated in the cervical carcinoma HeLa cells. Transfection of pDNA vectors encoding short-hairpin RNAs (shRNAs) reduced levels of EndoG mRNA in HeLa cells. In physiological circumstances, EndoG knockdown did not have an effect on the stability of pDNA or the levels of encoded transgene expression as measured over a four-day time course. However, when endogenous expression of EndoG was induced by an extrinsic stimulus, targeting of EndoG by shRNA improved the perceived stability and transgene expression of pDNA vectors. Therefore, EndoG is not a mediator of exogenous DNA clearance, but in non-physiological circumstances, it may nonspecifically cleave intracellular DNA regardless of its origin. These findings make it unlikely that targeting of EndoG is a viable strategy for improving the duration and level of transgene expression from nonviral DNA vectors in gene therapy efforts. PMID- 27260397 TI - 3-Acetyl-Chlorophyll Formation in Light-Harvesting Complexes of Purple Bacteria by Chemical Oxidation. AB - Dedicated to the memory of Yuriy Nikolayevich Kozlov Oxidation of bacteriochlorophyll (BChl) with potassium ferricyanide in membranes and LH2 complexes (carotenoid-less and control samples) from the purple bacteria Allochromatium minutissimum and Rhodobacter sphaeroides as well as BChl photobleaching in a model system have been studied. The oxidation of BChl depended on the type of bacteria. BChl850 was rapidly oxidized in samples from Alc. minutissimum, and BChl800 and BChl850 were slowly oxidized in samples from Rb. sphaeroides. The carotenoids were not involved in protecting BChl from chemical oxidation in the light-harvesting complexes. The appearance of BChl oxidation product was registered in the absorption spectra (absorption maximum about 700 nm) and by HPLC analysis. The oxidized BChl was identified as 3-acetyl chlorophyll. It differed from BChl by the presence of a double bond in pyrrole ring II at the 7-8 position. The extinction coefficient of 3-acetyl-chlorophyll was about 10 times less than that of BChl850 in the LH2 complex from Alc. minutissimum. In the BChl -> 3-acetyl-chlorophyll transition, the binding constant of the latter with LH2 complex as compared with that of BChl did not change dramatically, as indicated by: (i) preserved electrophoretic mobility of the complex; (ii) the presence of 3-acetyl-chlorophyll in the complex after separation; (iii) the presence of a 3-acetyl-chlorophyll CD signal that was proportional to its absorption spectrum. PMID- 27260398 TI - How Can Gastric Cancer Molecular Profiling Guide Future Therapies? AB - Gastric cancer is the third greatest global cause of cancer-related deaths. Despite its high prevalence, only recently have comprehensive genomic surveys shed light on its molecular alterations. As surgery is the only curative treatment strategy and chemotherapy has shown limited efficacy, new treatments are urgently needed. Many molecular therapies for gastric cancer have entered clinical trials but-apart from Trastuzumab and Ramucirumab-all have failed. We analyze the current knowledge of the genetic 'landscape' of gastric cancers, elaborating on novel, preclinical approaches. We posit that this knowledge lays the basis for identifying bona fide molecular targets and developing solid therapeutic approaches, requiring accurate patient selection and taking advantage of preclinical models to assist clinical development of novel combination strategies. PMID- 27260399 TI - Role of Bmznf-2, a Bombyx mori CCCH zinc finger gene, in masculinisation and differential splicing of Bmtra-2. AB - Deciphering the regulatory factors involved in Bombyx mori sex determination has been a puzzle, challenging researchers for nearly a century now. The pre-mRNA of B. mori doublesex (Bmdsx), a master regulator gene of sexual differentiation, is differentially spliced, producing Bmdsxm and Bmdsxf transcripts in males and females respectively. The putative proteins encoded by these differential transcripts orchestrate antagonistic functions, which lead to sexual differentiation. A recent study in B. mori illustrated the role of a W-derived fem piRNA in conferring femaleness. In females, the fem piRNA was shown to suppress the activity of a Z-linked CCCH type zinc finger (znf) gene, Masculiniser (masc), which indirectly promotes the Bmdsxm type of splicing. In this study, we report a novel autosomal (Chr 25) CCCH type znf motif encoding gene Bmznf-2 as one of the potential factors in the Bmdsx sex specific differential splicing, and we also provide insights into its role in the alternative splicing of Bmtra2 by using ovary derived BmN cells. Over-expression of Bmznf-2 induced Bmdsxm type of splicing (masculinisation) with a correspondingly reduced expression of Bmdsxf type isoform in BmN cells. Further, the site-directed mutational studies targeting the tandem CCCH znf motifs revealed their indispensability in the observed phenotype of masculinisation. Additionally, the dual luciferase assays in BmN cells using 5' UTR region of the Bmznf-2 strongly implied the existence of a translational repression over this gene. From these findings, we propose Bmznf-2 to be one of the potential factors of masculinisation similar to Masc. From the growing number of Bmdsx splicing regulators, we assume that the sex determination cascade of B. mori is quite intricate in nature; hence, it has to be further investigated for its comprehensive understanding. PMID- 27260400 TI - Our findings, my method: Framing science in televised interviews. AB - The public communication of science and technology largely depends on their framing in the news media, but scientists' role in this process has only been explored indirectly. This study focuses on storied accounts told by scientists when asked to present their research or provide expert advice in the course of a news interview. A total of 150 items from a current affairs talk show broadcast in the Israeli media were explored through a methodology combining narrative and conversation analysis. Using the concept of framing as originally proposed by Erving Goffman, we show that researchers use personal accounts as a way of reframing news stories introduced by the program hosts. Elements of method and rationale, which are usually considered technical and are shunned in journalistic reports, emerged as a crucial element in the accounts that experts themselves provided. The implications for framing research and science communication training are discussed. PMID- 27260401 TI - Meckel's and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible. AB - Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3Y367C/+ mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel's) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP BGJ398 corrects Meckel's and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3Y367C/+ mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders. PMID- 27260403 TI - Altered secondary structure of Dynorphin A associates with loss of opioid signalling and NMDA-mediated excitotoxicity in SCA23. AB - Spinocerebellar ataxia type 23 (SCA23) is caused by missense mutations in prodynorphin, encoding the precursor protein for the opioid neuropeptides alpha neoendorphin, Dynorphin (Dyn) A and Dyn B, leading to neurotoxic elevated mutant Dyn A levels. Dyn A acts on opioid receptors to reduce pain in the spinal cord, but its cerebellar function remains largely unknown. Increased concentration of or prolonged exposure to Dyn A is neurotoxic and these deleterious effects are very likely caused by an N-methyl-d-aspartate-mediated non-opioid mechanism as Dyn A peptides were shown to bind NMDA receptors and potentiate their glutamate evoked currents. In the present study, we investigated the cellular mechanisms underlying SCA23-mutant Dyn A neurotoxicity. We show that SCA23 mutations in the Dyn A-coding region disrupted peptide secondary structure leading to a loss of the N-terminal alpha-helix associated with decreased kappa-opioid receptor affinity. Additionally, the altered secondary structure led to increased peptide stability of R6W and R9C Dyn A, as these peptides showed marked degradation resistance, which coincided with decreased peptide solubility. Notably, L5S Dyn A displayed increased degradation and no aggregation. R6W and wt Dyn A peptides were most toxic to primary cerebellar neurons. For R6W Dyn A, this is likely because of a switch from opioid to NMDA- receptor signalling, while for wt Dyn A, this switch was not observed. We propose that the pathology of SCA23 results from converging mechanisms of loss of opioid-mediated neuroprotection and NMDA mediated excitotoxicity. PMID- 27260402 TI - Differential burden of rare protein truncating variants in Alzheimer's disease patients compared to centenarians. AB - We compared coding region variants of 53 cognitively healthy centenarians and 45 patients with Alzheimer's disease (AD), all of Ashkenazi Jewish (AJ) ancestry. Despite the small sample size, the known AD risk variant APOE4 reached genome wide significance, indicating the advantage of utilizing 'super-controls'. We restricted our subsequent analysis to rare variants observed at most once in the 1000 Genomes database and having a minor allele frequency below 2% in our AJ sample. We compared the burden of predicted protein altering variants between cases and controls as normalized by the level of rare synonymous variants. We observed an increased burden among AD subjects for predicted loss-of-function (LoFs) variants defined as stop-gain, frame shift, initiation codon (INIT) and splice site mutations (n = 930, OR = 1.3, P = 1.5*E-5). There was no enrichment across all rare protein altering variants defined as missense plus LoFs, in frame indels and stop-loss variants (n = 13 014, OR = 0.97, P = 0.47). Among LoFs, the strongest burden was observed for INIT (OR = 2.16, P = 0.0097) and premature stop variants predicted to cause non-sense-mediated decay in the majority of transcripts (NMD) (OR = 1.98, P = 0.02). Notably, this increased burden of NMD, INIT and splice variants was more pronounced in a set of 1397 innate immune genes (OR = 4.55, P = 0.0043). Further comparison to additional exomes indicates that the difference in LoF burden originated both from the AD and centenarian sample. In summary, we observed an overall increased burden of rare LoFs in AD subjects as compared to centenarians, and this enrichment is more pronounced for innate immune genes. PMID- 27260404 TI - ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism. AB - The role of post-transcriptional gene regulation in human brain development and neurodevelopmental disorders remains mostly uncharacterized. ELAV-like RNA binding proteins (RNAbps) are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission, both critical to the normal function of the brain in cognition and behavior. Here, we identify the downstream neuronal transcriptional and splicing networks of ELAVL2, an RNAbp with previously unknown function in the brain. Expression of ELAVL2 was reduced in human neurons and RNA-sequencing was utilized to identify networks of differentially expressed and alternatively spliced genes resulting from haploinsufficient levels of ELAVL2. These networks contain a number of autism-relevant genes as well as previously identified targets of other important RNAbps implicated in autism spectrum disorder (ASD) including RBFOX1 and FMRP. ELAVL2-regulated co-expression networks are also enriched for neurodevelopmental and synaptic genes, and include genes with human-specific patterns of expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal function and clinically relevant to ASD. PMID- 27260405 TI - Neuron-specific knock-down of SMN1 causes neuron degeneration and death through an apoptotic mechanism. AB - Spinal muscular atrophy is a devastating disease that is characterized by degeneration and death of a specific subclass of motor neurons in the anterior horn of the spinal cord. Although the gene responsible, survival motor neuron 1 (SMN1), was identified 20 years ago, it has proven difficult to investigate its effects in vivo. Consequently, a number of key questions regarding the molecular and cellular functions of this molecule have remained unanswered. We developed a Caenorhabditis elegans model of smn-1 loss-of-function using a neuron-specific RNA interference strategy to knock-down smn-1 selectively in a subclass of motor neurons. The transgenic animals presented a cell-autonomous, age-dependent degeneration of motor neurons detected as locomotory defects and the disappearance of presynaptic and cytoplasmic fluorescent markers in targeted neurons. This degeneration led to neuronal death as revealed by positive reactivity to genetic and chemical cell-death markers. We show that genes of the classical apoptosis pathway are involved in the smn-1-mediated neuronal death, and that this phenotype can be rescued by the expression of human SMN1, indicating a functional conservation between the two orthologs. Finally, we determined that Plastin3/plst-1 genetically interacts with smn-1 to prevent degeneration, and that treatment with valproic acid is able to rescue the degenerative phenotype. These results provide novel insights into the cellular and molecular mechanisms that lead to the loss of motor neurons when SMN1 function is reduced. PMID- 27260407 TI - Coacervation with surfactants: From single-chain surfactants to gemini surfactants. AB - Coacervation is a spontaneous process during which a colloidal dispersion separates into two immiscible liquid phases: a colloid-rich liquid phase in equilibrium with a diluted phase. Coacervation is usually divided into simple coacervation and complex coacervation according to the number of components. Surfactant-based coacervation normally contains traditional single-chain surfactants. With the development of surfactants, gemini surfactants with two amphiphilic moieties have been applied to form coacervation. This review summarizes the development of simple coacervation and complex coacervation in the systems of single-chain surfactants and gemini surfactants. Simple coacervation in surfactant solutions with additives or at elevated temperature and complex coacervation in surfactant/polymer mixtures by changing charge densities, molecular weight, ionic strength, pH, or temperature are reviewed. The comparison between gemini surfactants and corresponding monomeric single-chain surfactants reveals that the unique structures of gemini surfactants endow them with higher propensity to generate coacervation. PMID- 27260406 TI - Increased steroidogenesis promotes early-onset and severe vision loss in females with OPA1 dominant optic atrophy. AB - OPA1 mutations are responsible for autosomal dominant optic atrophy (ADOA), a progressive blinding disease characterized by retinal ganglion cell (RGC) degeneration and large phenotypic variations, the underlying mechanisms of which are poorly understood. OPA1 encodes a mitochondrial protein with essential biological functions, its main roles residing in the control of mitochondrial membrane dynamics as a pro-fusion protein and prevention of apoptosis. Considering recent findings showing the importance of the mitochondrial fusion process and the involvement of OPA1 in controlling steroidogenesis, we tested the hypothesis of deregulated steroid production in retina due to a disease-causing OPA1 mutation and its contribution to the visual phenotypic variations. Using the mouse model carrying the human recurrent OPA1 mutation, we disclosed that Opa1 haploinsufficiency leads to very high circulating levels of steroid precursor pregnenolone in females, causing an early-onset vision loss, abolished by ovariectomy. In addition, steroid production in retina is also increased which, in conjunction with high circulating levels, impairs estrogen receptor expression and mitochondrial respiratory complex IV activity, promoting RGC apoptosis in females. We further demonstrate the involvement of Muller glial cells as increased pregnenolone production in female cells is noxious and compromises their role in supporting RGC survival. In parallel, we analyzed ophthalmological data of a multicentre OPA1 patient cohort and found that women undergo more severe visual loss at adolescence and greater progressive thinning of the retinal nerve fibres than males. Thus, we disclosed a gender-dependent effect on ADOA severity, involving for the first time steroids and Muller glial cells, responsible for RGC degeneration. PMID- 27260408 TI - Juniperus rigida Sieb. extract inhibits inflammatory responses via attenuation of TRIF-dependent signaling and inflammasome activation. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Juniperus rigida Sieb. (J. rigida) is used for medicinal purposes in Asian countries to treat inflammation-related disorders, such as neuralgia, dropsy, and gout. AIM OF THE STUDY: The anti-inflammatory effects of J. rigida extract (JR) and its underlying mechanisms were explored both in in vitro cell lines and in vivo metabolic disease models. MATERIAL AND METHODS: Lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages were used to study the changes in inflammatory responses in vitro. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of JR on inflammasome activation. The murine model for monosodium urate (MSU)-induced peritonitis and high-fat diet (HFD)-induced type 2 diabetes were employed to study the effect of JR on in vivo efficacy. RESULTS: JR suppressed the MSU induced in vivo inflammatory response by attenuation of proinflammatory cytokines, including interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha). In the in vitro study, JR suppressed IL-1beta secretion via regulation of apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of inflammasome activation. JR also inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide (NO), TNF-alpha, and IL-6 in RAW264.7 cells. The inhibitory effects of JR were mediated through the regulation of the TRIF-dependent signaling pathway from JAK1/STAT1 phosphorylation. Furthermore, JR showed inhibitory effects on HFD induced type 2 diabetes in a mouse model through the regulation of blood glucose and serum IL-1beta. CONCLUSIONS: Our results indicate that JR attenuates both LPS stimulated and danger-signal-induced inflammatory responses in macrophages via regulation of the key inflammatory mechanisms, providing scientific support for its traditional use in the treatment of various inflammation-related metabolic disorders. PMID- 27260409 TI - Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng (Panax ginseng C. A. Meyer, Araliaceae) has been used as a traditional medicine for thousands of years for the treatment of a wide variety of diseases, including diabetes. Processed ginseng named Black ginseng exhibits more potent biological activities than white and red ginseng. The aim of this study was to investigate the effects of black ginseng extract (GBG05-FF) on hyperglycemia and glucose tolerance in streptozotocin (STZ)-induced diabetic mice. MATERIALS AND METHODS: Black ginseng was produced by a repeated steaming and drying process, subsequent extraction with 70% ethanol, filtration, and lyophilization. The effect of GBG05-FF on glucose uptake and related protein expression and phosphorylation were determined in C2C12 cells. Furthermore, we evaluated the anti-diabetic effects of GBG05-FF in STZ-induced diabetic mice. RESULTS: GBG05-FF significantly (p<0.05) increased glucose uptake in C2C12 myotubes via AMPK, Sirt1 and PI3-K pathway. In addition, GBG05-FF improved the fasting blood glucose levels and glucose tolerance in STZ-induced diabetic mice. GBG05-FF decreased blood parameters such as glycated hemoglobin, triglyceride and total cholesterol. Quantitative RT-PCR assay revealed that in the STZ-induced diabetic mice treated with GBG05-FF, the expression of hepatic genes involved in gluconeogenesis (phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase)), glycogenolysis (liver glycogen phosphorylase (LGP)) and glycogenesis (glycogen synthase (GS)) was suppressed, while the expression of the genes involved in glucose uptake (glucose transporter (GLUT) 1, GLUT4) and beta oxidation (acyl-CoA oxidase (ACO), carnitine palmitoyl transferase 1a (CPT1a), mitochondrial medium chain acyl-CoA dehydrogenase (MCAD)) in muscle were increased. GBG05-FF delayed diabetes-associated muscle atrophy by activating mTOR. The major bioactive compounds including ginsenoside Rg1, Rg3(S), Rg3(R), Rg5, Rk1 and Rh4 were evaluated for glucose uptake effect in C2C12 myotubes; the data indicated that Rh4 significantly (p<0.05) increased glucose uptake. CONCLUSION: Collectively, the results suggested that GBG05-FF is a potentially useful agent for treatment of diabetes by increasing glucose uptake. PMID- 27260410 TI - Antiplasmodial, anti-complement and anti-inflammatory in vitro effects of Biophytum umbraculum Welw. traditionally used against cerebral malaria in Mali. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Biophytum umbraculum Welw. (Oxalidaceae) is a highly valued African medicinal plant used for treatment of cerebral malaria, a critical complication of falciparum malaria. AIM OF THE STUDY: To provide additional information about traditional use of B. umbraculum and to test plant extracts and isolated compounds for in vitro activities related to cerebral malaria. MATERIALS AND METHODS: The traditional practitioners were questioned about indication, mode of processing/application, dosage and local name of B. umbraculum. Organic extracts and some main constituents of the plant were investigated for anti-malaria, anti-complement activity and inhibition of NO secretion in a RAW 264.7 cell line. RESULTS: Treatment of cerebral malaria was the main use of B. umbraculum (fidelity level 56%). The ethyl acetate extract showed anti-complement activity (ICH50 5.7+/-1.6MUg/ml), inhibition of macrophage activation (IC50 16.4+/-1.3MUg/ml) and in vitro antiplasmodial activity (IC50 K1 5.6+/-0.13MUg/ml, IC50 NF54 6.7+/-0.03MUg/ml). The main constituents (flavone C glycosides) did not contribute to the activity of the extract. CONCLUSION: Inhibition of complement activation and anti-inflammatory activity of B. umbraculum observed in this study might be possible targets for adjunctive therapy in cerebral malaria together with its antiplasmodial activity. However, clinical trials are necessary to evaluate the activity due to the complex pathogenesis of cerebral malaria. PMID- 27260411 TI - TLR2 signals via NF-kappaB to drive IL-15 production in salivary gland epithelial cells derived from patients with primary Sjogren's syndrome. AB - Toll-like receptors (TLRs) are pattern recognition receptors linking innate and adaptive immune responses, which resulted overexpressed in primary Sjogren's syndrome (pSS). Interleukin-15 (IL-15) is a pro-inflammatory cytokine which was recently demonstrated to be involved in pSS pathogenesis. The study was undertaken to clarify whether TLR2 is involved in the production of IL-15 in human salivary gland epithelial cells (SGEC) from pSS patients. SGEC primary cell cultures were established from pSS minor salivary gland tissues explanted from patients with a sure diagnosis of SS. After neutralization of TLR2 with a blocking monoclonal antibody, IL-15 production was assayed by immunoblotting and flow cytometry, IL-15 in the culture supernatants was measured by ELISA, and mRNA levels were assessed by RT-PCR and real-time PCR. The production of IL-15 by pSS SGEC decreased in culture supernatants and in protein lysates (p < 0.01) when TLR2 signaling was inhibited in pSS SGEC. In addition, a control at the transcriptional level was also detected; in fact, inhibition of nuclear factor (NF)-kappaB through the transfection of pSS SGEC with the dominant-negative inhibitory kappaBalpha proteins (IkappaBalpha) vector (IkappaBalphaDN) abrogated the stimulatory effect of TLR2 on IL-15 production. These data suggest that TLR2 activation is involved in the induction of IL-15 production by pSS SGEC and promotes inflammation through NF-kappaB activation. Therefore, therapeutic strategies that target TLR2/IL-15 pathway might be strong candidates for preventing or treating pSS. PMID- 27260412 TI - Alkaline hydrolysis to remove potentially infectious viral RNA contaminants from DNA. AB - BACKGROUND: Diagnostics and research of high-consequence animal disease agents is often limited to laboratories with a high level of biosecurity that restrict the transport of biological material. Often, sharing of DNA with external partners is needed to support diagnostics, forensics, or research. Even in the absence of virus, RNA from positive-sense single stranded RNA (+ssRNA) viruses that may contaminate otherwise purified DNA preparations continues to pose a threat due to its potential to be infectious via direct translation to yield viral proteins. While the risk of animal infection or accidental reconstitution and release of a virus from RNA is very low, the high impact of an animal disease event associated with the accidental release of some + ssRNA viruses, such as classical swine fever or foot-and-mouth disease viruses, necessitates the precaution of having procedures to ensure the complete inactivation of viruses and + ssRNA viral genomes. RNA and DNA are differentially susceptible to enzymatic degradations; however, such procedures are susceptible to unintended DNA damage and/or failure due to enzyme or cofactor instabilities. Therefore, we describe the development and verification of a robust and simple chemical and physical method to selectively degrade RNA from purified DNA preparations. The procedure employs incubation of DNA in 0.25 N sodium hydroxide at 65 degrees C for 1 h followed by neutralization and boiling for 10 min to hydrolyze contaminating RNA and inactivate animal disease viruses from DNA preparations. Additional critical quality control elements include use of a synthetic control RNA (SCR) and an SCR specific real-time RT-PCR to track effectiveness of the procedure in a parallel treated control sample, and a pH check of reagents to ensure proper neutralization of alkaline conditions. RESULTS: The new procedure reduced intact RNA beyond the limit of detection by realtime RT-PCR and inactivated viruses by in vitro culture infectivity assays. CONCLUSIONS: Treated DNA, while denatured, remains suitable for most common molecular biology procedures including PCR, transformation of E. coli, and molecular sequencing. The procedure ensures not only the inactivation of a variety of viruses but also the degradation through hydrolysis of potentially contaminating infectious + ssRNA viral genomes. PMID- 27260413 TI - FR-900098, an antimalarial development candidate that inhibits the non-mevalonate isoprenoid biosynthesis pathway, shows no evidence of acute toxicity and genotoxicity. AB - FR-900098 is an inhibitor of 1-deoxy-d-xylulose-5-phosphate (DXP) reductoisomerase, the second enzyme in the non-mevalonate isoprenoid biosynthesis pathway. In previous studies, FR-900098 was shown to possess potent antimalarial activity in vitro and in a murine malaria model. In order to provide a basis for further preclinical and clinical development, we studied the acute toxicity and genotoxicity of FR-900098. We observed no acute toxicity in rats, i.e. there were no clinical signs of toxicity and no substance-related deaths after the administration of a single dose of 3000 mg/kg body weight orally or 400 mg/kg body weight intravenously. No mutagenic potential was detected in the Salmonella typhimurium reverse mutation assay (Ames test) or an in vitro mammalian cell gene mutation test using mouse lymphoma L5178Y/TK(+/-) cells (clone 3.7.2C), both with and without metabolic activation. In addition, FR-900098 demonstrated no clastogenic or aneugenic capability or significant adverse effects on blood formation in an in vivo micronucleus test with bone marrow erythrocytes from NMRI mice. We conclude that FR-900098 lacks acute toxicity and genotoxicity, supporting its further development as an antimalarial drug. PMID- 27260427 TI - Fluorous-assisted metal chelate affinity extraction technique for analysis of protein kinase activity. AB - We have developed a fluorous affinity-based extraction method for measurement of protein kinase activity. In this method, a fluorescent peptide substrate was phosphorylated by a protein kinase, and the obtained phosphopeptide was selectively captured with Fe(III)-immobilized perfluoroalkyliminodiacetic acid reagent via a metal chelate affinity technique. Next, the captured phosphopeptide was selectively extracted into a fluorous solvent mixture, tetradecafluorohexane and 1H,1H,2H,2H-tridecafluoro-1-n-octanol (3:1, v/v), using the specificity of fluorous affinity (fluorophilicity). In contrast, the remained substrate peptide in the aqueous (non-fluorous) phase was easily measured fluorimetrically. Finally, the enzyme activity could be assayed by measuring the decrease in fluorescence. The feasibility of this method was demonstrated by applying the method for measurement of the activity of cAMP-dependent protein kinase (PKA) using its substrate peptide (kemptide) pre-labeled with carboxytetramethylrhodamine (TAMRA). PMID- 27260428 TI - Determination of phytate in high molecular weight, charged organic matrices by two-dimensional size exclusion-ion chromatography. AB - A two-dimensional chromatography method for analyzing phytate or other ionic targets in matrices containing high molecular weight, charged organic species is described. Prior to quantification by anion exchange chromatography, the sample matrix was prepared by size exclusion chromatography, which removed the majority of the matrix. Quantification of phytate on the AS11-HC was sensitive (0.25uM, 0.17mg/l) and reproducible (4.6% RSD) allowing this method to provide baseline separation of phytate from a manure extract within 14min. The method is simple, requiring only sample filtering, reproducible (between-run variation 5% RSD) and linear from 0.38 to 76uM (0.25-50mg/l). The method is suitable for routine determination of phytate in high organic matrices such as manure extracts. PMID- 27260429 TI - Ultrasensitive electrochemical immunosensor for quantitative detection of tumor specific growth factor by using Ag@CeO2 nanocomposite as labels. AB - In this paper, an ultrasensitive electrochemical immunosensor was developed for the detection of tumor specific growth factor (TSGF). Reduced graphene oxide tetraethylene pentamine (rGO-TEPA) was used to modify the surface of glassy carbon electrode (GCE). Meanwhile, Ag@CeO2 nanocomposite was synthesized and applied as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for the reduction of H2O2 was recorded. Simultaneously, electrochemical impedance spectroscopy (EIS) and Cyclic voltammetry (CV) were used to characterize the fabrication process of the immunosensor. The anti-TSGF primary antibody (Ab1) was immobilized onto the rGO-TEPA modified GCE via cross-linking with glutaraldehyde (GA). And then the TSGF antigen and Ab2-Ag@CeO2 were modified onto the electrode surface in sequence. Under the optimal conditions, the immunosensor exhibited a wide linear range (0.500-100pg/mL), a low detection limit (0.2pg/mL), good reproducibility, acceptable selectivity and excellent stability. The proposed sensing strategy may provide a potential application in the detection of other cancer biomarkers. PMID- 27260430 TI - Fe3O4@p-Naphtholbenzein as a novel nano-sorbent for highly effective removal and recovery of Berberine: Response surface methodology for optimization of ultrasound assisted dispersive magnetic solid phase extraction. AB - A hydrophobic surface modified iron oxide magnetic nano-sorbent was successfully synthesized, characterized and utilized for highly effective removal and recovery of Berberine (Brb) by Ultrasound Assisted Dispersive Magnetic Solid Phase Extraction (UADM-SPE). Fabrication of p-Naphtholbenzein-coated magnetic nanoparticles (PNB-MNPs) was certified by characteristic analyses such as: Fourier transform infrared spectroscopy (FT-IR), X-ray Diffraction (XRD), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The characterized PNB-MNPs were utilized to develop a UADM-SPE method for Brb, a well known isoquinoline alkaloid with a highlighted chemical skeleton for designing selective and powerful bioactive molecules. Affecting parameters on the extraction of Brb were optimized through an orthogonal rotatable central composite design (CCD). The optimum condition is obtained when the variables are set to: pH=4, amount of MNPs=20mg, sample volume=30ml, sonication time=1min at room temperature, and desorbing solvent=500uL of methanol. Under the mentioned condition, an extraction recovery of 98.2%, with relative standard deviation of 3.7%, was obtained via five replicated measurements on a 0.1mgL(-1) Brb standard solution. Finally, the method was successfully applied for determination of Brb in human plasma and urine samples. Regarding the method calibration graphs in plasma and urine matrices, spiked in the range of 0.01-200.00ugL(-1), pre concentration factors of 134 and 122, method detection limit (MDL) of 0.17 and 0.19ugL(-1), and lower limit of quantification of 0.57 and 0.63ugL(-1) were obtained for plasma and urine samples, respectively. The method exhibits good potentials to be a fast, efficient and reliable method for determination of Brb in human biological samples. PMID- 27260431 TI - Development of a MSFIA system for sequential determination of antimony, arsenic and selenium using hydride generation atomic fluorescence spectrometry. AB - This paper proposed a multisyringe flow injection analysis (MSFIA) system for antimony, arsenic and selenium determination in peanut samples by hydride generation atomic fluorescence spectrometry (HG-AFS). The optimization step of the hydride generation was performed using a two-level full factorial design involving the parameters: hydrochloric acid, sodium tetrahydroborate and potassium iodide concentrations. So, using the chemical conditions optimized, this method allows the determination of these elements employing the external calibration technique using aqueous standards with limits of detection and quantification of 0.04 and 0.14ugL(-1) for antimony, 0.04 and 0.14ugL(-1) for arsenic and 0.14 and 0.37ugL(-1) for selenium, respectively. Additionally, the effect of vanadium, chromium, cobalt, nickel, zinc, copper, iron and molybdenum on the generation of chemical vapour was also studied. The precision expressed as relative standard deviation varied from 1.2 to 3.6% for antimony, 1.8-3.9% for arsenic and 1.8-2% for selenium. The accuracy for arsenic and selenium was confirmed using the certified peach leaves reference material SRM 1547 produced by National Institute of Standard and Technology. The proposed method showed 45 injection throughput (h(-1)) using 1.6mL sample volume for each element, 0.8mL NaBH4 0.5% (w/v) containing NaOH 0.05% (w/v), 0.8mL HCl 5M and 0.4mL KI 14% (w/v) containing L-ascorbic acid 2.5% (w/v). The method was applied to the determination of antimony, arsenic and selenium in peanut samples, which were firstly lyophilized and afterward digested using microwave assisted radiation. Six samples were analyzed and the contents of the elements found were: 28.7 41.3ugkg(-1) for arsenic, 86.4-480.1ugkg(-1) for selenium and 32.6-52.4ugkg(-1) for antimony. Addition/recovery tests were also performed to confirm the method accuracy for the three elements. PMID- 27260426 TI - Molecular basis for photoreceptor outer segment architecture. AB - To serve vision, vertebrate rod and cone photoreceptors must detect photons, convert the light stimuli into cellular signals, and then convey the encoded information to downstream neurons. Rods and cones are sensory neurons that each rely on specialized ciliary organelles to detect light. These organelles, called outer segments, possess elaborate architectures that include many hundreds of light-sensitive membranous disks arrayed one atop another in precise register. These stacked disks capture light and initiate the chain of molecular and cellular events that underlie normal vision. Outer segment organization is challenged by an inherently dynamic nature; these organelles are subject to a renewal process that replaces a significant fraction of their disks (up to ~10%) on a daily basis. In addition, a broad range of environmental and genetic insults can disrupt outer segment morphology to impair photoreceptor function and viability. In this chapter, we survey the major progress that has been made for understanding the molecular basis of outer segment architecture. We also discuss key aspects of organelle lipid and protein composition, and highlight distributions, interactions, and potential structural functions of key OS resident molecules, including: kinesin-2, actin, RP1, prominin-1, protocadherin 21, peripherin-2/rds, rom-1, glutamic acid-rich proteins, and rhodopsin. Finally, we identify key knowledge gaps and challenges that remain for understanding how normal outer segment architecture is established and maintained. PMID- 27260432 TI - A sensitive acetylcholinesterase biosensor based on gold nanorods modified electrode for detection of organophosphate pesticide. AB - A sensitive amperometric acetylcholinesterase (AChE) biosensor, based on gold nanorods (AuNRs), was developed for the detection of organophosphate pesticide. Compared with Au@Ag heterogeneous NRs, AuNRs exhibited excellent electrocatalytic properties, which can electrocatalytically oxidize thiocholine, the hydrolysate of acetylthiocholine chloride (ATCl) by AChE at +0.55V (vs. SCE). The AChE/AuNRs/GCE biosensor was fabricated on basis of the inhibition of AChE activity by organophosphate pesticide. The biosensor could detect paraoxon in the linear range from 1nM to 5MUM and dimethoate in the linear range from 5nM to 1MUM, respectively. The detection limits of paraoxon and dimethoate were 0.7nM and 3.9nM, which were lower than the reported AChE biosensor. The proposed biosensor could restore to over 95% of its original current, which demonstrated the good reactivation. Moreover, the biosensor can be applicable to real water sample measurement. Thus, the biosensor exhibited low applied potential, high sensitivity and good stability, providing a promising tool for analysis of pesticides. PMID- 27260433 TI - Simple sensitive rapid detection of Escherichia coli O157:H7 in food samples by label-free immunofluorescence strip sensor. AB - A simple, one-step, rapid method to detect Escherichia coli O157: H7 (E. coli O157: H7) using a label-free immunofluorescence strip sensor is presented. Fluorescein isothiocyanate (FITC) was added to the sample culture medium to prepare the fluorescent probe for the label-free strip sensor. With the presence of E. coli O157: H7 in the samples, the bacteria could emit a yellow-green fluorescence after incubation and maintain good affinity to the monoclonal antibodies (McAb) against E. coli O157: H7. The direct-type immunofluorescence strip sensor was based on the binding between fluorescent bacteria and the unlabeled McAb immobilized at the test line in nitrocellulose membrane (NC membrane) reaction zone. The visual limit of detection (LOD) of the strip for qualitative detection was 10(6)cells/mL while the LOD for semi-quantitative detection could go down to 10(5)cells/mL by using scanning reader. The LOD was substantially improved to 1cells/mL of the original bacterial content after pre incubation of the bread, milk and jelly samples in broth for 10, 10 and 8h respectively, which was competitive to some current rapid E. coli O157: H7 detection methods. Besides the obvious advantages, including reduced detection time and operation procedures, the results of this method meet the various detection requirements for E. coli O157: H7 and are comparable to the traditional enzyme-linked immunosorbent assay (ELISA) and double antibody sandwich gold labeled strips. This is the first report of semi-quantitative immunofluorescence strip for directly detecting foodborne pathogen using only one unlabeled antibody. All detections could be achieved in less than 5min. In addition, this simple, low-cost and easy to be popularized method served as a significant step towards the development of monitoring foodborne pathogens in food-safety testing. PMID- 27260434 TI - Multiplexed detection of lung cancer biomarkers based on quantum dots and microbeads. AB - We have developed a multiplexed fluoroimmunoassay of three lung cancer biomarkers based on multicolor quantum dots (QDs) as detection elements and micro-magnetic beads as immune carriers. QDs have the ability to simplify multiplexed analysis. In our method, the fluorescent signals derived from three cross-talk-free QD conjugated probes with emission maxima at 525, 585 and 625nm could be analyzed to determine the concentrations of the target proteins. With this system, fragments of cytokeratin 19 (CYRFA 21-1), carcinoembryonic antigen (CEA), and neuron specific enolase (NSE), were simultaneously detected in a single sample with a low detection limit down to the 1.0ng/mL level (364pg/mL for CYRFA 21-1, 38pg/mL for CEA, 370pg/mL for NSE in a single detection). Additional advantages of the presented method include ease of operation, low cost, and a very low sample volume (20uL). PMID- 27260435 TI - Surface plasmon resonance biosensing: Approaches for screening and characterising antibodies for food diagnostics. AB - Research in biosensing approaches as alternative techniques for food diagnostics for the detection of chemical contaminants and foodborne pathogens has increased over the last twenty years. The key component of such tests is the biorecognition element whereby polyclonal or monoclonal antibodies still dominate the market. Traditionally the screening of sera or cell culture media for the selection of polyclonal or monoclonal candidate antibodies respectively has been performed by enzyme immunoassays. For niche toxin compounds, enzyme immunoassays can be expensive and/or prohibitive methodologies for antibody production due to limitations in toxin supply for conjugate production. Automated, self regenerating, chip-based biosensors proven in food diagnostics may be utilised as rapid screening tools for antibody candidate selection. This work describes the use of both single channel and multi-channel surface plasmon resonance (SPR) biosensors for the selection and characterisation of antibodies, and their evaluation in shellfish tissue as standard techniques for the detection of domoic acid, as a model toxin compound. The key advantages in the use of these biosensor techniques for screening hybridomas in monoclonal antibody production were the real time observation of molecular interaction and rapid turnaround time in analysis compared to enzyme immunoassays. The multichannel prototype instrument was superior with 96 analyses completed in 2h compared to 12h for the single channel and over 24h for the ELISA immunoassay. Antibodies of high sensitivity, IC50's ranging from 4.8 to 6.9ng/mL for monoclonal and 2.3-6.0ng/mL for polyclonal, for the detection of domoic acid in a 1min analysis time were selected. Although there is a progression for biosensor technology towards low cost, multiplexed portable diagnostics for the food industry, there remains a place for laboratory-based SPR instrumentation for antibody development for food diagnostics as shown herein. PMID- 27260436 TI - An automated flow injection system for metal determination by flame atomic absorption spectrometry involving on-line fabric disk sorptive extraction technique. AB - A novel flow injection-fabric disk sorptive extraction (FI-FDSE) system was developed for automated determination of trace metals. The platform was based on a minicolumn packed with sol-gel coated fabric media in the form of disks, incorporated into an on-line solid-phase extraction system, coupled with flame atomic absorption spectrometry (FAAS). This configuration provides minor backpressure, resulting in high loading flow rates and shorter analytical cycles. The potentials of this technique were demonstrated for trace lead and cadmium determination in environmental water samples. The applicability of different sol gel coated FPSE media was investigated. The on-line formed complex of metal with ammonium pyrrolidine dithiocarbamate (APDC) was retained onto the fabric surface and methyl isobutyl ketone (MIBK) was used to elute the analytes prior to atomization. For 90s preconcentration time, enrichment factors of 140 and 38 and detection limits (3sigma) of 1.8 and 0.4MUgL(-1) were achieved for lead and cadmium determination, respectively, with a sampling frequency of 30h(-1). The accuracy of the proposed method was estimated by analyzing standard reference materials and spiked water samples. PMID- 27260437 TI - Rapid estimation of readily leachable triazine residues in soils using automatic kinetic bioaccessibility assays followed by on-line sorptive clean-up as a front end to liquid chromatography. AB - An automatic batchwise bioaccessibility test was proposed for on-line monitoring of readily mobile pools of ametryn and atrazine residues in agricultural soils with different physicochemical properties. A 0.01molL(-1) CaCl2 solution mimicking rainwater percolation through the soil profiles was used for the herbicide extractions. The extract aliquots were successively sampled at regular time intervals in order to investigate the extraction kinetics. For extract clean up and retention of freely dissolved target species, 30mg of restricted-access like copolymer were used as in-line sorptive material followed by elution with methanol and on-line heart-cut injection towards a C18 silica reversed-phase monolithic column (100*4.6mm) in a liquid chromatographic system. A mathematical model emphasized that the readily available pools vs time can be in most instances described by a first-order exponential equation, thus an asymptotical value is approached. Consequently, the leaching assays can be performed without attaining chemical equilibrium. Enhancement factors and detection limits were 10.2 and 18.8, and 0.40 and 0.37mgkg(-1) for ametryn and atrazine, respectively. The automatic method features good repeatability for leaching tests (r.s.d.: 11.8 10.2% for sandy and 3.7-6.2% for clayey soil). Reliable data, demonstrated with relative recoveries in the soil leachates ranging from 86 to 104%, were achieved in less than 35min, thus avoiding the need for up to 24h as recommended by standard leaching methods. PMID- 27260438 TI - New optical paper sensor for in situ measurement of hydrogen sulphide in waters and atmospheres. AB - A novel and low-cost colorimetric sensor for the determination of hydrogen sulphide in environmental samples has been developed. This sensor is based on the immobilization of the reagent N,N-Dimethyl-p-phenylenediamine and FeCl3 in paper support, in which the H2S is adsorbed in order to give rise to the formation of methylene blue as reaction product. The sensor has been applied to determine H2S in water and air samples. Two different sampling systems for H2S caption from the air have been assayed: active and passive sampling. The analytical properties of the different systems have been obtained and compared. The analytical signals, corresponding to the methylene blue, have been obtained measuring the absorbance by conventional reflectance diffuse or using different algorithms for quantifying color intensity. The results obtained with both measurement procedures were comparable, with a detection limit of 1.11 and 1.12mLm(-3) for air samples (active and passive), and 0.5mgL(-1) for water samples. The developed sensor provides good accuracy and precision (RSD<12%) and simplifies significantly the analytical measurements because it avoids the need of preparing derivatization reagents, sample handling and allows in situ measurements. The reaction product obtained is highly stable in this support and no provide any blank signal. Under the optimal conditions, the proposed method exhibit excellent visual sensitivity for the naked eye procedure, making the detection of H2S possible. PMID- 27260439 TI - Bio-assisted potentiometric multisensor system for purity evaluation of recombinant protein A. AB - Recombinant proteins became essential components of drug manufacturing. Quality control of such proteins is routine task, which usually requires a lot of time, expensive reagents, specialized equipment and highly educated personnel. In this study we propose a new concept for protein purity evaluation that is based on application of bio-assisted potentiometric multisensor system. The model object for analysis was recombinant protein A from Staphylococcus aureus (SpA), which is commonly used for monoclonal antibody purification. SpA solutions with different amount of host cell related impurities (Escherichia coli, bacterial lysate) were analyzed. Two different bio-transducers were employed: proteinase K from Tritirachium album and baker's yeast Saccharomyces cerevisiae. It was shown that both bio-transducers are able to induce changes in pure and lysate-contaminated SpA samples. Different products of yeast digestion and proteolysis with proteinase of pure SpA and lysate were detected with size exclusion high performance liquid chromatography (SE-HPLC). The induced changes of chemical composition are detectible with potentiometric multisensor system and can be related to SpA purity through projection on latent structures (PLS) regression technique. The proposed method allows for estimation of the impurity content with 12% accuracy using proteinase K and 16% accuracy using baker's yeast. The suggested approach could be useful for early contamination warning at initial protein purification steps. The analysis requires no expensive materials and equipment, no bio-material immobilization, and its duration time is comparable with other commonly used methods like chromatography or electrophoresis though the main part of this time is related to the sample preparation. PMID- 27260440 TI - Comparison of the solid-phase extraction efficiency of a bounded and an included cyclodextrin-silica microporous composite for polycyclic aromatic hydrocarbons determination in water samples. AB - Solid-phase extraction is one of the most important techniques for sample purification and concentration. A wide variety of solid phases have been used for sample preparation over time. In this work, the efficiency of a new kind of solid phase extraction adsorbent, which is a microporous material made from modified cyclodextrin bounded to a silica network, is evaluated through an analytical method which combines solid-phase extraction with high-performance liquid chromatography to determine polycyclic aromatic hydrocarbons in water samples. Several parameters that affected the analytes recovery, such as the amount of solid phase, the nature and volume of the eluent or the sample volume and concentration influence have been evaluated. The experimental results indicate that the material possesses adsorption ability to the tested polycyclic aromatic hydrocarbons. Under the optimum conditions, the quantification limits of the method were in the range of 0.09-2.4MUgL(-1) and fine linear correlations between peak height and concentration were found around 1.3-70MUgL(-1). The method has good repeatability and reproducibility, with coefficients of variation under 8%. Due to the concentration results, this material may represent an alternative for trace analysis of polycyclic aromatic hydrocarbons in water trough solid-phase extraction. PMID- 27260441 TI - Ultra-trace level speciated isotope dilution measurement of Cr(VI) using ion chromatography tandem mass spectrometry in environmental waters. AB - The reliable analysis of highly toxic hexavalent chromium, Cr(VI), at ultra-trace levels remains challenging, given its easy conversion to non-toxic trivalent chromium. This work demonstrates a novel analytical method to quantify Cr(VI) at low ngL(-1) concentration levels in environmental water samples by using speciated isotope dilution (SID) analysis and double-spiking with Cr(III) and Cr(VI) enriched for different isotopes. Ion chromatography tandem mass spectrometry (IC-MS/MS) was used for the analysis of Cr(VI) as HCrO4(-) -> CrO3( ). Whereas the classical linear multipoint calibration (MPC) curve approach obtained a method detection limit (MDL) of 7ngL(-1) Cr(VI), the modified SID-MS method adapted from U. S. EPA 6800 allowed for the quantification of Cr(VI) with an MDL of 2ngL(-1) and provided results corrected for Cr(VI) loss occurred after sample collection. The adapted SID-MS approach proved to yield more accurate and precise results than the MPC method, allowed for compensation of Cr(VI) reduction during sample transportation and storage while eliminating the need for frequent external calibration. The developed method is a complementary tool to routinely used inductively-coupled plasma (ICP) MS and circumvents typically experienced interferences. PMID- 27260442 TI - A single use electrochemical sensor based on biomimetic nanoceria for the detection of wine antioxidants. AB - We report the development and characterization of a disposable single use electrochemical sensor based on the oxidase-like activity of nanoceria particles for the detection of phenolic antioxidants. The use of nanoceria in the sensor design enables oxidation of phenolic compounds, particularly those with ortho dihydroxybenzene functionality, to their corresponding quinones at the surface of a screen printed carbon electrode. Detection is carried out by electrochemical reduction of the resulting quinone at a low applied potential of -0.1V vs the Ag/AgCl electrode. The sensor was optimized and characterized with respect to particle loading, applied potential, response time, detection limit, linear concentration range and sensitivity. The method enabled rapid detection of common phenolic antioxidants including caffeic acid, gallic acid and quercetin in the uM concentration range, and demonstrated good functionality for the analysis of antioxidant content in several wine samples. The intrinsic oxidase-like activity of nanoceria shows promise as a robust tool for sensitive and cost effective analysis of antioxidants using electrochemical detection. PMID- 27260444 TI - Polydimethylsiloxane/metal-organic frameworks coated stir bar sorptive extraction coupled to gas chromatography-flame photometric detection for the determination of organophosphorus pesticides in environmental water samples. AB - In this work, the metal-organic frameworks (MOFs), MIL-101-Cr-NH2 was synthesized via a direct hydrothermal method, and a polydimethylsiloxane (PDMS)/MIL-101-Cr NH2 coated stir bar was prepared by sol-gel technique. Good reproducibility was obtained for the preparation of PDMS/MIL-101-Cr-NH2 coated stir bar with the relative standard deviations (RSDs) ranging from 3.7 to 5.2% (n=7) in one batch, and from 5.4 to 9.2% (n=7) among different batches. With the high surface area and rich benzene ring structure of MIL-101-Cr-NH2, the prepared PDMS/MIL-101-Cr NH2 coated stir bar presented higher extraction efficiency for target organophosphorus pesticides (OPPs, including phorate, diazinon, malathion, fenthion, quinalphos and ethion) over PDMS coated stir bar. Based on it, a new method of PDMS/MIL-101-Cr-NH2 coated stir bar sorptive extraction (SBSE) coupled to gas chromatography-flame photometric detection (GC-FPD) was proposed for the determination of six OPPs in environmental water samples. The operation parameters affecting the extraction efficiency of SBSE, including extraction time, stirring rate, desorption time and ionic strength, were investigated. Under the optimal conditions, the limits of detection (S/N=3) were found to be in the range of 0.043-0.085MUgL(-1) for the six target OPPs, and the linear range was 0.5-100MUgL(-1) for malathion and 0.2-100MUgL(-1) for other five OPPs. The RSDs of the proposed method evaluated at 1ugL(-1) for each OPP were in the range of 5.9-8.7% (intra-day, n=7) and 6.1-10.7% (inter-day, n=5), respectively. The enrichment factors were varied from 110 to 151-fold (theoretical enrichment factor was 200-fold). The proposed method was applied to the analysis of OPPs in East Lake and pond water samples with recoveries in the range of 89.3-115% and 80.0-113% for the spiked East Lake and pond water samples, respectively. PMID- 27260443 TI - Application of a nanostructured platform and imprinted sol-gel film for determination of chlorogenic acid in food samples. AB - Chlorogenic acid (CGA) is a polyphenol derivative that widely exists in higher plants like fruits, vegetables, black teas, and some traditional Chinese medicines. In this work, we have proposed a sensitive and selective electrochemical sensor for detection of CGA. The sensor was based on a glassy carbon electrode (GCE) modified with a functional platform by grafting vinyltrimethoxysilane (VTMS) in multi-walled carbon nanotubes (MWCNTs) and covered by a molecularly imprinted siloxane (MIS) film prepared using the sol-gel process. The VTMS was grafted onto the surface of the MWCNTs via in situ free radical polymerization. The MIS was obtained from the acid-catalyzed hydrolysis/condensation of a solution consisting of tetraethoxysilane (TEOS), phenyltriethoxysilane (PTEOS), (3-aminopropyl)trimethoxysilane (APTMS), and CGA as a template molecule. The modification procedure was evaluated by differential pulse voltammetry (DPV) and scanning electron microscopy (SEM). Under optimized operational conditions, a linear response was obtained covering a concentration ranging from 0.08MUmolL(-1) to 500MUmolL(-1) with a detection limit (LOD) of 0.032MUmolL(-1). The proposed sensor was applied to CGA determination in coffee, tomato, and apple samples with recoveries ranging from 99.3% to 108.6%, showing a promising potential application in food samples. Additionally, the imprinted sensor showed a significantly higher affinity for target CGA than the non imprinted siloxane (NIS) sensor. PMID- 27260445 TI - Non-enzymatic detection of glucose using poly(azure A)-nickel modified glassy carbon electrode. AB - A simple, sensitive and selective non-enzymatic glucose sensor was constructed in this paper. The poly(azure A)-nickel modified glassy carbon electrode was successfully fabricated by the electropolymerization of azure A and the adsorption of Ni(2+). The Ni modified electrode, which was characterized by scanning electron microscope, cyclic voltammetry, electrochemical impedance spectra and X-ray photoelectron spectroscopy measurements, respectively, displayed well-defined current responses of the Ni(III)/Ni(II) couple and showed a good activity for electrocatalytic oxidation of glucose in alkaline medium. Under the optimized conditions, the developed sensor exhibited a broad linear calibration range of 5 MUM-12mM for quantification of glucose and a low detection limit of 0.64MUM (3sigma). The excellent analytical performance including simple structure, fast response time, good anti-interference ability, satisfying stability and reliable reproducibility were also found from the proposed amperometric sensor. The results were satisfactory for the determination of glucose in human serum samples as comparison to those from a local hospital. PMID- 27260447 TI - Polypyrrole nanowire as an excellent solid phase microextraction fiber for bisphenol A analysis in food samples followed by ion mobility spectrometry. AB - A polypyrrole nanowire coated fiber was prepared and used in head-space solid phase microextraction coupled with ion mobility spectrometry (HS-SPME-IMS) to the analysis of bisphenol A (BPA) in canned food samples, for the first time. This fiber was synthesized by electrochemical oxidation of the monomer in aqueous solution. The fiber characterization by scanning electron microscopy (SEM) revealed that the new fiber exhibited two-dimensional structures with a nanowire morphology. The effects of important extraction parameters on the efficiency of HS-SPME were investigated and optimized. Under the optimum conditions, the linearity of 10-150ngg(-1) and limit of detection (based on S/N=3) of 1ngg(-1) were obtained in BPA analysis. The repeatability (n=5) expressed as the relative standard deviation (RSD%) was 5.8%. At the end, the proposed method was successfully applied to determine BPA in various canned food samples (peas, corns, beans). Relative recoveries were obtained 93-96%. Method validation was conducted by comparing our results with those obtained through HPLC with fluorescence detection (FLD). Compatible results indicate that the proposed method can be successfully used in BPA analysis. This method is simple and cheaper than chromatographic methods, with no need of extra organic solvent consumption and derivatization prior to sample introduction. PMID- 27260446 TI - Thiazole orange as a fluorescent probe: Label-free and selective detection of silver ions based on the structural change of i-motif DNA at neutral pH. AB - Silver ions have been widely applied to many fields and have harmful effects on environments and human health. Herein, a label-free optical sensor for Ag(+) detection is constructed based on thiazole orange (TO) as a fluorescent probe for the recognition of i-motif DNA structure change at neutral pH. Ag(+) can fold a C rich single stranded DNA sequence into i-motif DNA structure at neutral pH and that folding is reversible by chelation with cysteine (Cys). The DNA folding process can be indicated by the fluorescence change of TO, which is non fluorescent in free molecule state and emits strong fluorescence after the incorporation with i-motif DNA. Thus, a rapid, sensitive, and selective method for the detection of Ag(+) and Cys is developed with a detection limit of 17 and 280nM, respectively. It is worth noting that the mechanism underlying the increase of the fluorescence of thiazole orange in the presence of i-motif structure is explained. Moreover, a fluorescent DNA logic gate is successfully designed based on the Ag(+)/Cys-mediated reversible fluorescence changes. The proposed detection strategy is label-free and economical. In addition, this system shows a great promise for i-motif/TO complex to analyze Ag(+) in the real samples. PMID- 27260448 TI - A sensitive and selective on-line amperometric sulfite biosensor using sulfite oxidase immobilized on a magnetite-gold-folate nanocomposite modified carbon paste electrode. AB - We describe a novel amperometric sulfite biosensor, comprising a carbon-paste electrode (Fe3O4@Au-Cys-FA/CPE) modified with immobilized sulfite oxidase (SOx) on a gold-coated magnetite nanoparticle core, encased within a conjugated folic acid (FA) cysteine (Cys) shell. The biosensor electrode was fabricated using a polydimethylsiloxane (PDMS) and mineral oil mixture as binder, which also enhances the physical stability and sensitivity of the electrode. The developed biosensor displays good electrocatalytic activity toward oxidation of H2O2, which occurs by an enzymatic reaction between SOx and sulfite. The Fe3O4@Au-Cys-FA electrode exhibits good electrocatalytic activity, and has good retention of chemisorbed SOx on the electrode because of its large surface area. Sulfite was quantified using amperometric measurements from the Fe3O4@Au-Cys-FA/CPE biosensor, and using an in-house assembled flow cell at +0.35V (vs. Ag/AgCl), with a phosphate buffer carrier (0.10M, pH 7.0) at a flow rate of 0.8mLmin(-1). The system detects sulfite over the range 0.1-200mgL(-1) (r(2)=0.998), with a detection limit of 10ugL(-1) (3sigma of blank). The system exhibits acceptable precision (%R.S.D.=3.1%), rapid sample throughput (109samplesh(-1)), and good stability (2w). The developed biosensor shows satisfactory tolerance to potential interferences, such as sugars, anions, ascorbic acid, and ethanol. We applied the developed method to the determination of sulfite content in wines and pickled food extracts, and our results are in good agreement with those obtained by the standard iodometric method. PMID- 27260449 TI - Establishment of local searching methods for orbitrap-based high throughput metabolomics analysis. AB - Our method aims to establish local endogenous metabolite databases economically without purchasing chemical standards, giving strong bases for following orbitrap based high throughput untargeted metabolomics analysis. A new approach here is introduced to construct metabolite databases on the base of biological sample analysis and mathematic extrapolation. Building local metabolite databases traditionally requires expensive chemical standards, which is barely affordable for most research labs. As a result, most labs working on metabolomics analysis have to refer public libraries, which is time consuming and limited for high throughput analysis. Using this strategy, a high throughput orbitrap based metabolomics platform can be established at almost no cost within a couple of months. It enables to facilitate the application of high throughput metabolomics analysis to identify disease-related biomarkers or investigate biological functions using orbitrap. PMID- 27260450 TI - An electrochemical genosensor for Leishmania major detection based on dual effect of immobilization and electrocatalysis of cobalt-zinc ferrite quantum dots. AB - Identification of Leishmania parasites is important in diagnosis and clinical studies of leishmaniasis. Although epidemiological and clinical methods are available, they are not sufficient for identification of causative agents of leishmaniasis. In the present study, quantum dots of magnetic cobalt-zinc ferrite (Co0.5Zn0.5Fe2O4) were synthesized and characterized by physicochemical methods. The quantum dots were then employed as an electrode modifier to immobilize a 24 mer specific single stranded DNA probe, and fabrication of a label-free, PCR-free and signal-on electrochemical genosensor for the detection of Leishmania major. Hybridization of the complementary single stranded DNA sequence with the probe under the selected conditions was explored using methylene blue as a redox marker, utilizing the electrocatalytic effect of the quantum dots on the methylene blue electroreduction process. The genosensor could detect a synthetic single stranded DNA target in a range of 1.0*10(-11) to 1.0*10(-18)molL(-1) with a limit of detection of 2.0*10(-19)molL(-1), and genomic DNA in a range of 7.31*10(-14) to 7.31*10(-6)ngMUL(-1) with a limit of detection of 1.80*10( 14)ngMUL(-1) with a high selectivity and sensitivity. PMID- 27260451 TI - Chemometric study of Andalusian extra virgin olive oils Raman spectra: Qualitative and quantitative information. AB - Authentication of extra virgin olive oil (EVOO) is an important topic for olive oil industry. The fraudulent practices in this sector are a major problem affecting both producers and consumers. This study analyzes the capability of FT Raman combined with chemometric treatments of prediction of the fatty acid contents (quantitative information), using gas chromatography as the reference technique, and classification of diverse EVOOs as a function of the harvest year, olive variety, geographical origin and Andalusian PDO (qualitative information). The optimal number of PLS components that summarizes the spectral information was introduced progressively. For the estimation of the fatty acid composition, the lowest error (both in fitting and prediction) corresponded to MUFA, followed by SAFA and PUFA though such errors were close to zero in all cases. As regards the qualitative variables, discriminant analysis allowed a correct classification of 94.3%, 84.0%, 89.0% and 86.6% of samples for harvest year, olive variety, geographical origin and PDO, respectively. PMID- 27260452 TI - Ultrasensitive detection of explosives and chemical warfare agents by low pressure photoionization mass spectrometry. AB - On-spot monitoring of threat agents needs high sensitive instrument. In this study, a low-pressure photoionization mass spectrometer (LPPI-MS) was employed to detect trace amounts of vapor-phase explosives and chemical warfare agent mimetics under ambient conditions. Under 10-s detection time, the limits of detection of 2,4-dinitrotoluene, nitrotoluene, nitrobenzene, and dimethyl methyl phosphonate were 30, 0.5, 4, and 1 parts per trillion by volume, respectively. As compared to those obtained previously with PI mass spectrometric techniques, an improvement of 3-4 orders of magnitude was achieved. This study indicates that LPPI-MS will open new opportunities for the sensitive detection of explosives and chemical warfare agents. PMID- 27260453 TI - Sensitive determination of As (III) and As (V) by magnetic solid phase extraction with Fe@polyethyleneimine in combination with hydride generation atomic fluorescence spectrometry. AB - The magnetic nanomaterial Fe@polyethyleneimine (Fe@PEI) was successfully synthesized and used as an effective adsorbent material for magnetic solid phase extraction(MSPE) of As(III) and As(V) from water samples. Fe@SiO2 nanoparticles were prepared by one pot synthetic method using a borohydride reduction method, then modified with (3-chloropropyl)trimethoxysilane to obtain Fe@SiO2-Cl by chloropropylation, which was reacted with PEI to achieve Fe@polyethyleneimine (Fe@PEI). The microstructure and morphology of Fe@PEI were characterized by transmission electron microscoscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). The experimental results showed that Fe@PEI demonstrated excellent adsorption for As(III) and As(V). Based on this fact, the determination method for these two arsenic species earned good limits of detection (LODs) of 0.002MUgL(-1) and wide calibration curves in the concentration range from 0.008 to 0.2MUgL(-1). The precisions of As (III) and As (V)were 1.95% and 2.55% (RSD, n=6), respectively. The proposed method was validated with real samples and the spiked recoveries were in the range of 82.7 98.3% and the accuracies were in the range of 2-13.3%. The results demonstrated that the developed MSPE method had good advantages such as simplicity, rapid separation, low cost, easy to reuse and high-quality analytical performances, which made it attractive for rapid and efficient extraction of inorganic arsenic species in the environmental water samples. PMID- 27260454 TI - A novel procedure for phase separation in dispersive liquid-liquid microextraction based on solidification of the aqueous phase. AB - In this paper, an alternative for handling the organic phase after a dispersive liquid-liquid microextraction using organic solvents lighter than water is presented. It is based on solidification (at -18 degrees C) of the aqueous phase obtained after centrifugation, and the decantation, collection and analysis of the liquid organic layer. The extraction of nicotine in toluene, and its determination in eggplant samples was conducted as a proof of concept. The study has been carried out using standards prepared in water and the formation of the dispersion was assisted by sonication. The organic extract was analysed using gas chromatography coupled to mass spectrometry. Satisfactory analytical figures of merit as: limit of detection (0.4ugL(-1), 2ngg(-1) wet sample), limit of quantification (1.2ugL(-1), 6.5ngg(-1) wet sample), within-day precision (RSD=7%), and linearity interval (up to 384ugL(-1) nicotine) were achieved. It constituted a contribution to the handling of organic extracts after microextraction processes. PMID- 27260455 TI - A novel approach for identification of biologically active phenolic compounds in complex matrices using hybrid quadrupole-orbitrap mass spectrometer: A promising tool for testing antimicrobial activity of hops. AB - The phenolic compounds, secondary metabolites of hops represent a large family of compounds that could be subsequently divided into smaller groups based on the similarities between their chemical structures. The antibacterial, antifungal and antiviral properties of hops are well known, but there is a lack of information about antimicrobial activities of individual hop compounds. This study was carried out with an objective to identify compounds present in hops that have potential antibacterial activity. In the first stage of experiment, the active compounds with potential anti-microbial activity had to be extracted from hop cones. Therefore, minced hop cones were applied on solid growth medium inoculated with Staphylococcus aureus. The active substances that migrated into the medium created an inhibition zone. In the second stage of experiment, the inhibition zones were cut out from Petri dishes, active compounds were extracted from these zones and consequently analyzed using LC-HRMS. These complex assays were developed and optimized. The data were acquired by using a quadrupole-orbitrap hybrid mass spectrometer by targeted-MS2 experiment in both ionization modes. The MS method has been developed as a screening method with a subsequent fragmentation of compound of interest on the base of inclusion mass list. The unknown compounds extracted from inhibition zones have been identified either by searching against a database or their structure has been elucidated on the basis of their fragmentation spectra. On the basis of this experiment the list of active compounds with potential anti-microbial activities was enhanced. PMID- 27260456 TI - Label-free electrochemical aptasensing of the human prostate-specific antigen using gold nanospears. AB - Gold nanospears were electrodeposited with the assistance of arginine as a soft template and precise selection of experimental parameters. The nanospears were then employed as a transducer to immobilize an aptamer of prostate-specific antigen (PSA) and fabrication of a label-free electrochemical aptasensor. The aptasensor was employed for the detection of PSA with a linear concentration range of 0.125-200ngmL(-1) and a limit of detection of 50pgmL(-1). The aptasensor was successfully applied to detect PSA in blood serum samples of healthy and patient persons. PMID- 27260457 TI - Plasmonically amplified bioassay - Total internal reflection fluorescence vs. epifluorescence geometry. AB - This paper investigates plasmonic amplification in two commonly used optical configurations for fluorescence readout of bioassays - epifluorescence (EPF) and total internal reflection fluorescence (TIRF). The plasmonic amplification in the EPF configuration was implemented by using crossed gold diffraction grating and Kretschmann geometry of attenuated total reflection method (ATR) was employed in the TIRF configuration. Identical assay, surface architecture for analyte capture, and optics for the excitation, collection and detection of emitted fluorescence light intensity were used in both TIRF and EPF configurations. Simulations predict that the crossed gold diffraction grating (EPF) can amplify the fluorescence signal by a factor of 10(2) by the combination of surface plasmon-enhanced excitation and directional surface plasmon-coupled emission in the red part of spectrum. This factor is about order of magnitude higher than that predicted for the Kretschmann geometry (TIRF) which only took advantage of the surface plasmon-enhanced excitation. When applied for the readout of sandwich interleukin 6 (IL-6) immunoassay, the plasmonically amplified EPF geometry designed for Alexa Fluor 647 labels offered 4-times higher fluorescence signal intensity compared to TIRF. Interestingly, both geometries allowed reaching the same detection limit of 0.4pM despite of the difference in the fluorescence signal enhancement. This is attributed to inherently lower background of fluorescence signal for TIRF geometry compared to that for EPF which compensates for the weaker fluorescence signal enhancement. The analysis of the inflammation biomarker IL-6 in serum at medically relevant concentrations and the utilization of plasmonic amplification for the fluorescence measurement of kinetics of surface affinity reactions are demonstrated for both EPF and TIRF readout. PMID- 27260458 TI - Microwave-assisted wet digestion with H2O2 at high temperature and pressure using single reaction chamber for elemental determination in milk powder by ICP-OES and ICP-MS. AB - In this work a green digestion method which only used H2O2 as an oxidant and high temperature and pressure in the single reaction chamber system (SRC-UltraWaveTM) was applied for subsequent elemental determination by inductively coupled plasma based techniques. Milk powder was chosen to demonstrate the feasibility and advantages of the proposed method. Samples masses up to 500mg were efficiently digested, and the determination of Ca, Fe, K, Mg and Na was performed by inductively coupled plasma optical emission spectrometry (ICP-OES), while trace elements (B, Ba, Cd, Cu, Mn, Mo, Pb, Sr and Zn) were determined by inductively coupled plasma mass spectrometry (ICP-MS). Residual carbon (RC) lower than 918mgL(-1) of C was obtained for digests which contributed to minimizing interferences in determination by ICP-OES and ICP-MS. Accuracy was evaluated using certified reference materials NIST 1549 (non-fat milk powder certified reference material) and NIST 8435 (whole milk powder reference material). The results obtained by the proposed method were in agreement with the certified reference values (t-test, 95% confidence level). In addition, no significant difference was observed between results obtained by the proposed method and conventional wet digestion using concentrated HNO3. As digestion was performed without using any kind of acid, the characteristics of final digests were in agreement with green chemistry principles when compared to digests obtained using conventional wet digestion method with concentrated HNO3. Additionally, H2O2 digests were more suitable for subsequent analysis by ICP-based techniques due to of water being the main product of organic matrix oxidation. The proposed method was suitable for quality control of major components and trace elements present in milk powder in consonance with green sample preparation. PMID- 27260459 TI - Precise and rapid isotopomic analysis by (1)H-(13)C 2D NMR: Application to triacylglycerol matrices. AB - An optimized HSQC sequence was tested and applied to triacylglycerol matrices to determine their isotopic and metabolomic profiles. Spectral aliasing and non uniform sampling approaches were used to decrease the experimental time and to improve the resolution, respectively. An excellent long-term repeatability of signal integrals was achieved enabling to perform isotopic measurements. Thirty two commercial vegetable oils were analyzed by this methodology. The results show that this method can be used to classify oil samples according to their geographical and botanical origins. PMID- 27260460 TI - New development in carbon quantum dots technical applications. AB - As a newly emerged member in carbon nanomaterials family, carbon quantum dots (CQDs) attracted everincreasing attention owing to their ultracompact size, excellent photoluminescence, favorable biocompatibility, versatile surface and superior electron transfer ability. The past decade has witnessed continuous advancements in the production of CQDs with high photoluminescence quantum yields for various applications. Herein, we track the newest development of CQDs with advanced physicochemical properties and their applications in sensing, bioimaging, nanomedicine and catalysis, and propose the challenges and perspectives in this exciting and promising field. PMID- 27260461 TI - Photoelectrochemical sensing of 4-chlorophenol based on Au/BiOCl nanocomposites. AB - The Au/BiOCl composites have been prepared by a facile one-pot ethylene glycol (EG) assisted solvothermal reaction in the presence of ionic liquid 1-hexadecyl-3 methylimidazolium chloride ([C16mim]Cl). During the synthesis procedure, the [C16mim]Cl has been used as Cl source, solvent of this system, and dispersing agent to effectively disperse Au on the surface of BiOCl. The as-prepared samples have been systematically characterized by multiple instruments to investigate the structure, morphology, and photoelectrochemical properties. According to the photoelectrochemical data, the Au/BiOCl composites exhibit better photoelectrochemical performance toward the detection of 4-chlorophenol than that of the pure BiOCl. The photocurrent response of Au/BiOCl modified electrode is high and stable under light irradiation. The proposed Au/BiOCl modified electrode shows a wide linear response ranging from 0.16 to 20mgL(-1) with detection limit of 0.05mgL(-1). It indicates a dramatically promising application of bismuth oxyhalides in photoelectrochemical detection. It will be expected that the present study may be lightly extended to the monitor of other organic pollutants by photoelectrochemical detection of the Au/BiOCl composites. PMID- 27260462 TI - Anthocyanins as inflammatory modulators and the role of the gut microbiota. AB - The health benefits of consuming fruits that are rich in polyphenols, especially anthocyanins, have been the focus of recent in vitro and in vivo investigations. Thus, greater attention is being directed to the reduction of the inflammatory process associated with the intestinal microbiota and the mechanism underlying these effects because the microbiota has been closely associated with the metabolism of these compounds in the gastrointestinal tract. Further interest lies in the ability of these metabolites to modulate the growth of specific intestinal bacteria. Thus, this review examines studies involving the action of the anthocyanins that are present in many fruits and their effect in the modulating the inflammatory process associated with the interaction between the host and the gut microbiota. The findings of both in vitro and in vivo studies suggest a potential antiinflammatory effect of these compounds, which seem to inhibit activation of the signaling pathway mediated by the transcription factor NFkappaB. This effect is associated with modulation of a beneficial gut microbiota, particularly an increase in Bifidobacterium strains. PMID- 27260463 TI - The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-kappaB activation. AB - Lipopolysaccharide (LPS) is the major structural component of Gram-negative bacteria cell wall and a highly pro-inflammatory toxin. Naringenin is found in Citrus fruits and exhibits antioxidant and anti-inflammatory properties through inhibition of NF-kappaB activation but its effects in LPS-induced inflammatory pain and leukocyte recruitment were not investigated yet. We investigated the effects of naringenin in mechanical hyperalgesia, thermal hyperalgesia and leukocyte recruitment induced by intraplantar injection of LPS in mice. We found that naringenin reduced hyperalgesia to mechanical and thermal stimuli, myeloperoxidase (MPO, a neutrophil and macrophage marker) and N-acetyl-beta-D glucosaminidase (NAG, a macrophage marker) activities, oxidative stress and cytokine (TNF-alpha, IL-1beta, IL-6, and IL-12) production in the paw skin. In the peritoneal cavity, naringenin reduced neutrophil and mononuclear cell recruitment, and abrogated MPO and NAG activity, cytokine and superoxide anion production, and lipid peroxidation. In vitro, pre-treatment with naringenin inhibited superoxide anion and cytokine (TNF-alpha, IL-1beta, IL-6, and IL-12) production by LPS-stimulated RAW 264.7 macrophages. Finally, we demonstrated that naringenin inhibited NF-kappaB activation in vitro and in vivo. Therefore, naringenin is a promising compound to treat LPS-induced inflammatory pain and leukocyte recruitment. PMID- 27260464 TI - Cu(II)-coumestrol interaction leads to ROS-mediated DNA damage and cell death: a putative mechanism for anticancer activity. AB - Phytoestrogens have attracted considerable interest as natural alternatives to hormone replacement therapy and their potential as cancer therapeutic agents. Among phytoestrogens, coumestrol has shown multipharmacological properties such as antiinflammatory, neuroprotective, osteoblastic differentiation and anticancer. Though several studies have described anticancer effects of coumestrol, a clear underlying molecular mechanism has not been elucidated. Unlike normal cells, cancer cells contain elevated copper levels that play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper in cancer cells can serve as effective anticancer strategy. Using human peripheral lymphocytes, we assessed lipid peroxidation, protein carbonylation, reactive oxygen species (ROS) generation, DNA damage and apoptosis by coumestrol in the presence of exogenously added Cu(II) in cells to simulate malignancy-like condition. Results showed that Cu(II)-coumestrol interaction leads to lipid peroxidation and protein carbonylation (markers of oxidative stress), DNA fragmentation and apoptosis in treated lymphocytes. Further, incubation of lymphocytes with ROS scavengers and membrane-permeant copper chelator, neocuproine, resulted in inhibition of DNA damage and apoptosis. This suggests that coumestrol engages in redox cycling of Cu(II) to generate ROS that leads to DNA fragmentation and apoptosis. In conclusion, this is the first report showing that coumestrol targets cellular copper to induce prooxidant death in malignant cells. We believe that such a prooxidant cytotoxic mechanism better explains the anticancer activity of coumestrol. These findings will provide significant insights into the development of new chemical molecules with better copper chelating and prooxidant properties against cancer cells. PMID- 27260465 TI - A conjugated fatty acid present at high levels in bitter melon seed favorably affects lipid metabolism in hepatocytes by increasing NAD(+)/NADH ratio and activating PPARalpha, AMPK and SIRT1 signaling pathway. AB - alpha-Eleostearic acid (alpha-ESA), or the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid, is a special fatty acid present at high levels in bitter melon seed oil. The aim of this study was to examine the effect of alpha ESA on hepatic lipid metabolism. Using H4IIEC3 hepatoma cell line, we showed that alpha-ESA significantly lowered intracellular triglyceride accumulation compared to alpha-linolenic acid (LN), used as a fatty acid control, in a dose- and time dependent manner. The effects of alpha-ESA on enzyme activities and mRNA profiles in H4IIEC3 cells suggested that enhanced fatty acid oxidation and lowered lipogenesis were involved in alpha-ESA-mediated triglyceride lowering effects. In addition, alpha-ESA triggered AMP-activated protein kinase (AMPK) activation without altering sirtuin 1 (SIRT1) protein levels. When cells were treated with vehicle control (VC), LN alone (LN; 100MUmol/L) or in combination with alpha-ESA (LN+alpha-ESA; 75+25MUmol/L) for 24h, acetylation of forkhead box protein O1 was decreased, while the NAD(+)/NADH ratio, mRNA levels of NAMPT and PTGR1 and enzyme activity of nicotinamide phosphoribosyltransferase were increased by LN+alpha-ESA treatment compared to treatment with LN alone, suggesting that alpha-ESA activates SIRT1 by increasing NAD(+) synthesis and NAD(P)H consumption. The antisteatosis effect of alpha-ESA was confirmed in mice treated with a high sucrose diet supplemented with 1% alpha-ESA for 5weeks. We conclude that alpha ESA favorably affects hepatic lipid metabolism by increasing cellular NAD(+)/NADH ratio and activating PPARalpha, AMPK and SIRT1 signaling pathways. PMID- 27260466 TI - Cardioprotective effects of lipoic acid, quercetin and resveratrol on oxidative stress related to thyroid hormone alterations in long-term obesity. AB - This study investigated possible mechanisms for cardioprotective effects of lipoic acid (LA), quercetin (Q) and resveratrol (R) on oxidative stress related to thyroid hormone alterations in long-term obesity. Female C57BL/6 mice were fed on high-fat diet (HFD), HFD+LA, HFD+R, HFD+Q and normal diet for 26weeks. Body weight, blood pressure, thyroid hormones, oxidative stress markers, angiotensin converting enzyme (ACE), nitric oxide synthase (NOS) and ion pump activities were measured, and expression of cardiac genes was analyzed by real-time polymerase chain reaction. HFD induced marked increase (P<.05) in body weight, blood pressure and oxidative stress, while plasma triidothyronine levels reduced. ACE activity increased (P<.05) in HFD mice (0.69+/-0.225U/mg protein) compared with controls (0.28+/-0.114U/mg protein), HFD+LA (0.231+/-0.02U/mg protein) and HFD+Q (0.182+/-0.096U/mg protein) at 26weeks. Moreover, Na(+)/K(+)-ATPase and Ca(2+) ATPase activities increased in HFD mice whereas NOS reduced. A 1.5-fold increase in TRalpha1 and reduction in expression of the deiodinase iodothyronine DIO1, threonine protein kinase and NOS3 as well as up-regulation of AT1alpha, ACE, ATP1B1, GSK3beta and Cja1 genes also occurred in HFD mice. Conversely, LA, Q and R inhibited weight gain; reduced TRalpha1 expression as well as increased DIO1; reduced ACE activity and AT1alpha, ATP1B1 and Cja1 gene expression as well as inhibited GSK3beta; increased total antioxidant capacity, GSH and catalase activity; and reduced blood pressure. In conclusion, LA, resveratrol and quercetin supplementation reduces obesity thereby restoring plasma thyroid hormone levels and attenuating oxidative stress in the heart and thus may have therapeutic potential in heart diseases. PMID- 27260467 TI - Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR gamma associated mechanisms. AB - Our previous study demonstrated that quercetin-metabolite-enriched plasma (QP) but not quercetin itself upregulates peroxisome proliferator-activated receptor gamma (PPAR-gamma) expression to induce G2/M arrest in A549 cells. In the present study, we incubated A549 cells with QP as well as quercetin-3-glucuronide (Q3G) and quercetin-3'-sulfate (Q3'S), two major metabolites of quercetin, to investigate the effects of quercetin metabolites on cell invasion and migration, the possible mechanisms and the role of PPAR-gamma. We also compared the effects of QP with those of quercetin and troglitazone (TGZ), a PPAR-gamma ligand. The results showed that QP significantly suppressed cell invasion and migration, as well as matrix metalloproteinases (MMPs)-2 activity and expression in a dose dependent manner. The effects of 10% QP on those parameters were similar to those of 10MUM quercetin and 20MUM TGZ. However, QP and TGZ rather than quercetin itself increased the expressions of nm23-H1 and tissue inhibitor of metalloproteinase (TIMP-2). Furthermore, we demonstrated that Q3G and Q3'S also inhibited the protein expression of MMP-2. GW9662, a PPAR-gamma antagonist, significantly diminished such an effect of Q3G and Q3'S. Silencing PPAR-gamma expression in A549 cells also significantly diminished the suppression effect of Q3G and Q3'S on MMP-2 expression. Taken together, our study demonstrated that QP inhibited cell invasion and migration through nm23-H1/TIMP-2/MMP-2 associated mechanisms. The upregulation of PPAR-gamma by quercetin metabolites such as Q3G and Q3'S could play an important role in the effects of QP. PMID- 27260469 TI - Caffeine suppresses the progression of human glioblastoma via cathepsin B and MAPK signaling pathway. AB - Glioblastoma has aggressive proliferative and invasive properties. We investigated the effect of caffeine on the invasion and the anti-cancer effect in human glioblastomas. Caffeine reduced the invasion in U-87MG, GBM8401 and LN229 cells. Caffeine decreased mRNA, protein expression, and activity of cathepsin B. Besides, mRNA and protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was upregulated by caffeine treatment, whereas matrix metalloproteinase 2 (MMP-2) was downregulated. The expression of Ki67, p-p38, phospforylated extracellular regulated protein kinases (p-ERK), and membranous integrin beta1 and beta3 was decreased by caffeine. The Rho-associated protein kinase (ROCK) inhibitor, Y27632, blocked the caffeine-mediated reduction of cathepsin B, phosphorylated focal adhesion kinase (p-FAK), and p-ERK, and invasion. Moreover, caffeine decreased the tumor size, cathepsin B and Ki67 expression in animal model. Caffeine reduced the invasion of glioma cells through ROCK-cathepsin B/FAK/ERK signaling pathway and tumor growth in orthotopic xenograft animal model, supporting the anti-cancer potential in glioma therapy. PMID- 27260468 TI - Epigenetic modifications of triterpenoid ursolic acid in activating Nrf2 and blocking cellular transformation of mouse epidermal cells. AB - Ursolic acid (UA), a well-known natural triterpenoid found in abundance in blueberries, cranberries and apple peels, has been reported to possess many beneficial health effects. These effects include anticancer activity in various cancers, such as skin cancer. Skin cancer is the most common cancer in the world. Nuclear factor E2-related factor 2 (Nrf2) is a master regulator of antioxidative stress response with anticarcinogenic activity against UV- and chemical-induced tumor formation in the skin. Recent studies show that epigenetic modifications of Nrf2 play an important role in cancer prevention. However, the epigenetic impact of UA on Nrf2 signaling remains poorly understood in skin cancer. In this study, we investigated the epigenetic effects of UA on mouse epidermal JB6 P+ cells. UA inhibited cellular transformation by 12-O-tetradecanoylphorbol-13-acetate at a concentration at which the cytotoxicity was no more than 25%. Under this condition, UA induced the expression of the Nrf2-mediated detoxifying/antioxidant enzymes heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 and UDP glucuronosyltransferase 1A1. DNA methylation analysis revealed that UA demethylated the first 15 CpG sites of the Nrf2 promoter region, which correlated with the reexpression of Nrf2. Furthermore, UA reduced the expression of epigenetic modifying enzymes, including the DNA methyltransferases DNMT1 and DNMT3a and the histone deacetylases (HDACs) HDAC1, HDAC2, HDAC3 and HDAC8 (Class I) and HDAC6 and HDAC7 (Class II), and HDAC activity. Taken together, these results suggest that the epigenetic effects of the triterpenoid UA could potentially contribute to its beneficial effects, including the prevention of skin cancer. PMID- 27260470 TI - Amelioration of neuronal cell death in a spontaneous obese rat model by dietary restriction through modulation of ubiquitin proteasome system. AB - Dietary restriction (DR) has been shown to increase longevity, delay onset of aging, reduce DNA damage and oxidative stress and prevent age-related decline of neuronal activity. We previously reported the role of altered ubiquitin proteasome system (UPS) in the neuronal cell death in a spontaneous obese rat model (WNIN/Ob rat). In this study, we investigated the effect of DR on obesity induced neuronal cell death in a rat model. Two groups of 40-day-old WNIN/Ob rats were either fed ad libitum (Ob) or pair-fed with lean. The lean phenotype of WNIN/Ob rats served as ad libitum control. These animals were maintained for 6.5months on their respective diet regime. At the end of the study, cerebral cortex was collected and markers of UPS, endoplasmic reticulum (ER) stress and autophagy were analyzed by quantitative real-time polymerase chain reaction, immunoblotting and immunohistochemistry. Chymotrypsin-like activity of proteasome was assayed by the fluorimetric method. Apoptotic cells were analyzed by TUNEL assay. DR improved metabolic abnormalities in obese rats. Alterations in UPS (up regulation of UCHL1, down-regulation of UCHL5, declined proteasomal activity), increased ER stress, declined autophagy and increased expression of alpha synuclein, p53 and BAX were observed in obese rats and DR alleviated these changes in obese rats. Further, DR decreased TUNEL-positive cells. In conclusion, DR in obese rats could not only restore the metabolic abnormalities but also preserved neuronal health in the cerebral cortex by preventing alterations in the UPS. PMID- 27260471 TI - Amelioration of obesity-associated inflammation and insulin resistance in c57bl/6 mice via macrophage polarization by fish oil supplementation. AB - Enormous phenotypic plasticity makes macrophages the target cells in obesity associated inflammatory diseases. Thus, nutritional components that polarize macrophages toward antiinflammatory phenotype can partially reverse inflammatory diseases like insulin resistance. In the present study, macrophage-polarizing and insulin-sensitizing properties of fish oil (FO) were evaluated in obese insulin resistant c57bl/6 mice fed high-fat diet (HFD-IR) after oral supplementation with FO (4, 8 or 16mg/kg body weight) and compared to lean and HFD-IR mice. FO supplemented HFD-IR mice exhibited reduced adiposity index, serum cholesterol and triglycerides and increased insulin sensitization and showed improved adipose tissue physiology under light and transmission electron microscopy. NF-kappaB/P65 expression showed a downward shift on FO supplementation. The surface marker of M1 macrophages (CD-86) and the TLR-4 expression reduced with the increased supplementation of FO. Expression of arginase 1, an important marker of M2 macrophages, increased in a dose-dependent manner in response to FO dosage, which was observed at protein level by the western blotting and at mRNA level by real time PCR. The cytokine profile of adipose tissue macrophages showed a steep shift toward antiinflammatory ones (IL-4 and IL-10) from the inflammatory TNF-alpha, IFN-gamma, IL-2 and IL-1beta. Thus, macrophage polarization seems to be the plausible mechanism via which FO alleviates obesity-induced inflammation and insulin resistance. PMID- 27260472 TI - Impact of colonialism on Maori and Aboriginal healthcare access: a discussion paper. AB - BACKGROUND: Historical socio-political processes have produced gross inequity of health resource for Aboriginal Australians and New Zealand Maori. OBJECTIVES: This paper argues that socio-political factors resulting from the entrenchment of colonialism have produced significant personal and structural barriers to the utilisation of healthcare services and directly impact the health status of these two vulnerable groups. DESIGN: Discussion Paper. CONCLUSIONS: Understanding the actual barriers preventing the utilisation of healthcare facilities, as perceived by Indigenous people, is essential in reducing the gross disparity between Indigenous and non-Indigenous morbidity and mortality in Australia and New Zealand. PMID- 27260473 TI - Corrigendum to "Physiological and molecular mechanisms associated with cross tolerance between hypoxia and low temperature in Thaumatotibia leucotreta" [J. Insect Physiol. 82 (2015) 75-84]. PMID- 27260474 TI - Bioremediation of wastewater from edible oil refinery factory using oleaginous microalga Desmodesmus sp. S1. AB - Edible oil industry produced massive wastewater, which requires extensive treatment to remove pungent smell, high phosphate, carbon oxygen demand (COD), and metal ions prior to discharge. Traditional anaerobic and aerobic digestion could mainly reduce COD of the wastewater from oil refinery factories (WEORF). In this study, a robust oleaginous microalga Desmodesmus sp. S1 was adapted to grow in WEORF. The biomass and lipid content of Desmodesmus sp. S1 cultivated in the WEORF supplemented with sodium nitrate were 5.62 g.L(-1) and 14.49%, whereas those in the WEORF without adding nitrate were 2.98 g.L(-1) and 21.95%. More than 82% of the COD and 53% of total phosphorous were removed by Desmodesmus sp. S1. In addition, metal ions, including ferric, aluminum, manganese and zinc were also diminished significantly in the WEORF after microalgal growth, and pungent smell vanished as well. In comparison with the cells grown in BG-11 medium, the cilia like bulges and wrinkles on the cell surface of Desmodesmus sp. S1 grown in WEORF became out of order, and more polyunsaturated fatty acids were detected due to stress derived from the wastewater. The study suggests that growing microalgae in WEORF can be applied for the dual roles of nutrient removal and biofuel feedstock production. PMID- 27260475 TI - Effect of the Femtosecond Laser on an Intracorneal Inlay for Surgical Compensation of Presbyopia during Cataract Surgery: Scanning Electron Microscope Imaging. AB - PURPOSE: To investigate the effect of the femtosecond laser-assisted cataract surgery (FLACS) on porcine eyes implanted with a Kamra corneal inlay and to describe how the inlay may change the effect of the femtosecond laser on the lens. METHODS: FLACS was performed on six porcine eyes and a Kamra corneal inlay had been implanted, exploring the lens under the surgical microscope. Another Kamra corneal inlay was attached to the upper part of the transparent hemisphere used for calibration of the femtosecond laser. Capsulorhexis, arcuate incisions, and phacofragmentation were carried out. The Kamra corneal inlay was compared with a nontreated one using a scanning electron microscope (SEM), and the hemisphere was analyzed with a surgical microscope. RESULTS: Capsulorhexis and phacofragmentation were completed in all the porcine eyes, although accuracy to determine the exact effect on the lens was not possible to achieve. The effect of the femtosecond laser on the PMMA hemisphere through the Kamra corneal inlay showed the capsulorhexis was placed outside the outer margin of the inlay and a sharply sculpted fragmentation pattern with a three-dimensional (donut-shaped) annulus untreated beneath it. SEM images of the nontreated and the treated inlays were comparable. No ultrastructural changes were found in the treated Kamra corneal inlay. CONCLUSIONS: FLACS can be performed with a Kamra corneal inlay for surgical compensation of presbyopia without the risk of damaging the inlay. The Kamra corneal inlay acts as a screen that avoids the laser to reach the areas beneath its shadow, but not the exposed areas of the lens. PMID- 27260476 TI - How to improve vital sign data quality for use in clinical decision support systems? A qualitative study in nine Swedish emergency departments. AB - BACKGROUND: Vital sign data are important for clinical decision making in emergency care. Clinical Decision Support Systems (CDSS) have been advocated to increase patient safety and quality of care. However, the efficiency of CDSS depends on the quality of the underlying vital sign data. Therefore, possible factors affecting vital sign data quality need to be understood. This study aims to explore the factors affecting vital sign data quality in Swedish emergency departments and to determine in how far clinicians perceive vital sign data to be fit for use in clinical decision support systems. A further aim of the study is to provide recommendations on how to improve vital sign data quality in emergency departments. METHODS: Semi-structured interviews were conducted with sixteen physicians and nurses from nine hospitals and vital sign documentation templates were collected and analysed. Follow-up interviews and process observations were done at three of the hospitals to verify the results. Content analysis with constant comparison of the data was used to analyse and categorize the collected data. RESULTS: Factors related to care process and information technology were perceived to affect vital sign data quality. Despite electronic health records (EHRs) being available in all hospitals, these were not always used for vital sign documentation. Only four out of nine sites had a completely digitalized vital sign documentation flow and paper-based triage records were perceived to provide a better mobile workflow support than EHRs. Observed documentation practices resulted in low currency, completeness, and interoperability of the vital signs. To improve vital sign data quality, we propose to standardize the care process, improve the digital documentation support, provide workflow support, ensure interoperability and perform quality control. CONCLUSIONS: Vital sign data quality in Swedish emergency departments is currently not fit for use by CDSS. To address both technical and organisational challenges, we propose five steps for vital sign data quality improvement to be implemented in emergency care settings. PMID- 27260477 TI - Neurospora chromosomes are organized by blocks of importin alpha-dependent heterochromatin that are largely independent of H3K9me3. AB - Eukaryotic genomes are organized into chromatin domains with three-dimensional arrangements that presumably result from interactions between the chromatin constituents-proteins, DNA, and RNA-within the physical constraints of the nucleus. We used chromosome conformation capture (3C) followed by high-throughput sequencing (Hi-C) with wild-type and mutant strains of Neurospora crassa to gain insight into the role of heterochromatin in the organization and function of the genome. We tested the role of three proteins thought to be important for establishment of heterochromatin, namely, the histone H3 lysine 9 methyltransferase DIM-5, Heterochromatin Protein 1 (HP1), which specifically binds to the product of DIM-5 (trimethylated H3 lysine 9 [H3K9me3]), and DIM-3 (importin alpha), which is involved in DIM-5 localization. The average genome configuration of the wild-type strain revealed strong intra- and inter chromosomal associations between both constitutive and facultative heterochromatic domains, with the strongest interactions among the centromeres, subtelomeres, and interspersed heterochromatin. Surprisingly, loss of either H3K9me3 or HP1 had only mild effects on heterochromatin compaction, whereas dim-3 caused more drastic changes, specifically decreasing interactions between constitutive heterochromatic domains. Thus, associations between heterochromatic regions are a major component of the chromosome conformation in Neurospora, but two widely studied key heterochromatin proteins are not necessary, implying that undefined protein factors play key roles in maintaining overall chromosome organization. PMID- 27260478 TI - Percutaneous radiofrequency ablation for patients with malignant lung tumors: a phase II prospective multicenter study (JIVROSG-0702). AB - PURPOSE: This prospective multicenter study aimed to evaluate the efficacy and safety of percutaneous radiofrequency (RF) ablation for lung cancer. MATERIALS AND METHODS: From May 2008 to April 2012, 33 patients (26 men, 7 women; mean age 70.5 years) were enrolled. RF ablation was performed using an internally cooled or expandable multitined electrode. The primary endpoint was complete response (CR) determined using (18)F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) performed 6 months after RF ablation. The secondary endpoint was the incidence and grade of adverse events (AEs) evaluated using the Common Toxicity Criteria for Adverse Events, version 3.0. RESULTS: All patients underwent RF ablation and had efficacy analyses evaluated; however, FDG-PET/CT images before RF ablation were not available for two patients. The CR rate was 68 % (21 of 31 patients). One patient had a grade 5 AE unrelated to RF ablation. Grade >=3 AEs occurred in 12 % of patients. During the follow-up period (median 37 months; range 1-55 months), five patients developed local tumor progression and nine (29 %) died. Overall survival at 1, 2, and 3 years was 97, 82, and 74 %, respectively. CONCLUSION: Percutaneous RF ablation is a safe, feasible, and effective treatment for small malignant lung tumors. PMID- 27260479 TI - Ecotoxicological risks of the abandoned F-Ba-Pb-Zn mining area of Osor (Spain). AB - Due to its potential toxic properties, metal mobilization is of major concern in areas surrounding Pb-Zn mines. In the present study, metal contents and toxicity of soils, aqueous extracts from soils and mine drainage waters from an abandoned F-Ba-Pb-Zn mining area in Osor (Girona, NE Spain) were evaluated through chemical extractions and ecotoxicity bioassays. Toxicity assessment in the terrestrial compartment included lethal and sublethal endpoints on earthworms Eisenia fetida, arthropods Folsomia candida and several plant species, whereas aquatic tests involved bacteria Vibrio fischeri, microalgae Raphidocelis subcapitata and crustaceans Daphnia magna. Total concentrations of Ba (250-5110 mg kg-1), Pb (940 to >5000 mg kg-1) and Zn (2370-11,300 mg kg-1) in soils exceeded intervention values to protect human health. Risks for the aquatic compartment were identified in the release of drainage waters and in the potential leaching and runoff of metals from contaminated soils, with Cd (1.98-9.15 ug L-1), Pb (2.11-326 ug L-1) and Zn (280-2900 ug L-1) concentrations in filtered water samples surpassing US EPA Water Quality Criteria (2016a, b). Terrestrial ecotoxicity tests were in accordance with metal quantifications and identified the most polluted soil as the most toxic. Avoidance and reproduction tests with earthworms showed the highest sensitivity to metal contamination. Aquatic bioassays performed in aqueous extracts from soils confirmed the results from terrestrial tests and also detected toxic effects caused by the mine drainage waters. Algal growth inhibition was the most sensitive aquatic endpoint. In view of the results, the application of a containment or remediative procedure in the area is encouraged. PMID- 27260480 TI - State-of-the-lagoon reports as vehicles of cross-disciplinary integration. AB - An integrative approach across disciplines is needed for sustainable lagoon and estuary management as identified by integrated coastal zone management. The ARCH research project (Architecture and roadmap to manage multiple pressures on lagoons) has taken initial steps to overcome the boundaries between disciplines and focus on cross-disciplinary integration by addressing the driving forces, challenges, and problems at various case study sites. A model was developed as a boundary-spanning activity to produce joint knowledge and understanding. The backbone of the model is formed by the interaction between the natural and human systems, including economy and governance-based subsystems. The model was used to create state-of-the-lagoon reports for 10 case study sites (lagoons and estuarine coastal areas), with a geographical distribution covering all major seas surrounding Europe. The reports functioned as boundary objects to build joint knowledge. The experiences related to the framing of the model and its subsequent implementation at the case study sites have resulted in key recommendations on how to address the challenges of cross-disciplinary work required for the proper management of complex social-ecological systems such as lagoons, estuarine areas, and other land-sea regions. Cross-disciplinary integration is initially resource intensive and time consuming; one should set aside the required resources and invest efforts at the forefront. It is crucial to create engagement among the group of researchers by focusing on a joint, appealing overall concept that will stimulate cross-sectoral thinking and focusing on the identified problems as a link between collected evidence and future management needs. Different methods for collecting evidence should be applied including both quantitative (jointly agreed indicators) and qualitative (narratives) information. Cross-disciplinary integration is facilitated by functional boundary objects. Integration offers important rewards in terms of developing a better understanding and subsequently improved management of complex social-ecological systems. Integr Environ Assess Manag 2016;12:690-700. (c) 2016 SETAC. PMID- 27260483 TI - Murine fundus fluorescein angiography: An alternative approach using a handheld camera. AB - In today's modern pharmacologic approach to treating sight-threatening retinal vascular disorders, there is an increasing demand for a compact, mobile, lightweight and cost-effective fluorescein fundus camera to document the effects of antiangiogenic drugs on laser-induced choroidal neovascularization (CNV) in mice and other experimental animals. We have adapted the use of the Kowa Genesis Df Camera to perform Fundus Fluorescein Angiography (FFA) in mice. The 1 kg, 28 cm high camera has built-in barrier and exciter filters to allow digital FFA recording to a Compact Flash memory card. Furthermore, this handheld unit has a steady Indirect Lens Holder that firmly attaches to the main unit, that securely holds a 90 diopter lens in position, in order to facilitate appropriate focus and stability, for photographing the delicate central murine fundus. This easily portable fundus fluorescein camera can effectively record exceptional central retinal vascular detail in murine laser-induced CNV, while readily allowing the investigator to adjust the camera's position according to the variable head and eye movements that can randomly occur while the mouse is optimally anesthetized. This movable image recording device, with efficiencies of space, time, cost, energy and personnel, has enabled us to accurately document the alterations in the central choroidal and retinal vasculature following induction of CNV, implemented by argon-green laser photocoagulation and disruption of Bruch's Membrane, in the experimental murine model of exudative macular degeneration. PMID- 27260481 TI - Inflammasome and toll-like receptor signaling in human monocytes after successful cardiopulmonary resuscitation. AB - BACKGROUND: Whole body ischemia-reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) induces a generalized inflammatory response which contributes to the development of post-cardiac arrest syndrome (PCAS). Recently, pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and inflammasomes, have been shown to mediate the inflammatory response in IRI. In this study we investigated monocyte PRR signaling and function in PCAS. METHODS: Blood samples were drawn in the first 12 hours, and at 24 and 48 hours following return of spontaneous circulation in 51 survivors after cardiac arrest. Monocyte mRNA levels of TLR2, TLR4, interleukin-1 receptor-associated kinase (IRAK)3, IRAK4, NLR family pyrin domain containing (NLRP)1, NLRP3, AIM2, PYCARD, CASP1, and IL1B were determined by real-time quantitative PCR. Ex vivo cytokine production in response to stimulation with TLR ligands Pam3CSK4 and lipopolysaccharide (LPS) was assessed in both whole blood and monocyte culture assays. Ex vivo cytokine production of peripheral blood mononuclear cells (PBMCs) from a healthy volunteer in response to stimulation with patients' sera with or without LPS was assessed. The results were compared to 19 hemodynamically stable patients with coronary artery disease. RESULTS: Monocyte TLR2, TLR4, IRAK3, IRAK4, NLRP3, PYCARD and IL1B were initially upregulated in patients following cardiac arrest. The NLRP1 and AIM2 inflammasomes were downregulated in resuscitated patients. There was a significant positive correlation between TLR2, TLR4, IRAK3 and IRAK4 expression and the degree of ischemia as assessed by serum lactate levels and the time until return of spontaneous circulation. Nonsurvivors at 30 days had significantly lower mRNA levels of TLR2, IRAK3, IRAK4, NLRP3 and CASP1 in the late phase following cardiac arrest. We observed reduced proinflammatory cytokine release in response to both TLR2 and TLR4 activation in whole blood and monocyte culture assays in patients after CPR. Sera from resuscitated patients attenuated the inflammatory response in cultured PBMCs after co-stimulation with LPS. CONCLUSIONS: Successful resuscitation from cardiac arrest results in changes in monocyte pattern recognition receptor signaling pathways, which may contribute to the post-cardiac arrest syndrome. TRIAL REGISTRATION: The trial was registered in the German Clinical Trials Register ( DRKS00009684 ) on 27/11/2015. PMID- 27260482 TI - Ultrashort versus Conventional Anatomic Cementless Femoral Stems in the Same Patients Younger Than 55 Years. AB - BACKGROUND: Because the clinical and radiographic performance of an ultrashort anatomic cementless stem has been investigated in only two randomized controlled studies, well-designed trials should aim for a thorough comparison of the outcomes of ultrashort anatomic cementless and conventional anatomic cementless stems. QUESTIONS/PURPOSES: The purposes of this study were to compare (1) the clinical results, including Harris hip score, thigh pain, and WOMAC index score, (2) radiographic results, (3) bone mineral density; and (4) proportions of patients undergoing revision of a THA using an ultrashort anatomic cementless stem versus a conventional anatomic cementless stem in the same patients who underwent bilateral sequential THAs under the same anesthetic. METHODS: Two hundred patients (mean age, 53 years; range, 26-54 years) who underwent bilateral sequential THAs received an ultrashort anatomic cementless stem in one hip and a conventional anatomic cementless stem in the contralateral hip. From January 2004 to December 2005, we performed 524 same-day bilateral short and conventional anatomic cementless THAs in 262 patients, of whom 212 (81%) participated in this study. Five patients were lost to followup before 2 years, five were lost between 2 to 10 years, and two were lost between 10 to 13 years, leaving 200 patients. Patients who had end-stage bilateral hip disease and were younger than 55 years were selected for inclusion. The predominant diagnoses were osteonecrosis (118 patients, 59%) and osteoarthritis (44 patients, 22%). One hundred thirty-eight were men and 62 were women. At the time of each followup, the patients were assessed clinically and radiographically. In addition, each patient completed the WOMAC and the University of California Los Angeles (UCLA) activity scores. The minimum followup was 10 years (mean, 11.8 years; range, 10-13 years). Followups were done in person, with all images and followup clinic notes. Based on the power analysis, we estimated a sample size of 178 hips was needed in each group to detect a 3-point difference in the Harris hip score with 80% power. RESULTS: At the latest followup, there were no differences between the two groups regarding the mean Harris hip scores (94 versus 94 points; p = 0.189), mean WOMAC scores (17 versus 16 points; p = 0.191), or mean UCLA activity scores (9 versus 9 points; p = 0.381). Two patients in the ultrashort stem group and one patient in the conventional stem group had severe (9 points) thigh pain, and 30 patients (15%) in the conventional stem group had mild thigh pain (2 or 3 points) after vigorous exercise. Bone mineral density in the ultrashort and conventional stem groups, respectively, was greater in the ultrashort stem group than in the conventional stem group. Bone mineral density in Zone 1 at 12 years was 3.29 versus 1.88 g/cm(2) (p = 0.021), and 2.97 versus 0.91 g/m(2) in Zone 7 (p = 0.001). With the numbers available, there were no differences between the stem designs in terms of the proportion undergoing revision (one hip, 0.5%, in the short-stem group versus one hip, 0.5%, in the conventional group; p = 1.881). CONCLUSIONS: At followup into the second decade, ultrashort stems showed no differences from conventional cementless stems in terms of validated outcomes scores or fixation, although less stress shielding was observed. Reduction of stress shielding may reduce the long-term risk of periprosthetic fracture, but this was not shown in our study. LEVEL OF EVIDENCE: Level I, therapeutic study. PMID- 27260484 TI - Solar ultraviolet radiation cataract. AB - Despite being a treatable disease, cataract is still the leading cause for blindness in the world. Solar ultraviolet radiation is epidemiologically linked to cataract development, while animal and in vitro studies prove a causal relationship. However, the pathogenetic pathways for the disease are not fully understood and there is still no perfect model for human age related cataract. This non-comprehensive overview focus on recent developments regarding effects of solar UV radiation wavebands on the lens. A smaller number of fundamental papers are also included to provide a backdrop for the overview. Future studies are expected to further clarify the cellular and subcellular mechanisms for UV radiation-induced cataract and especially the isolated or combined temporal and spatial effects of UVA and UVB in the pathogenesis of human cataract. Regardless of the cause for cataract, there is a need for advances in pharmaceutical or other treatment modalities that do not require surgical replacement of the lens. PMID- 27260485 TI - Poly (I:C)-DOTAP cationic nanoliposome containing multi-epitope HER2-derived peptide promotes vaccine-elicited anti-tumor immunity in a murine model. AB - In the current study we aimed at developing a vaccine delivery/adjuvant system to enhance anti-tumor immunity against the natural multi-epitope HER2/Neu-derived P5 peptide. Polyriboinosinic: polyribocytidylic acid [Poly (I:C)] is a strong immunoadjuvant able to enhance specific antitumor immunity induced by peptide based vaccines. Nevertheless, delivering the peptide and adjuvant intracellularly into their target site remains a challenging issue. We hypothesized this barrier could be overcome through the use of a cationic nanoliposome carrier system which can carry and protect the antigen and adjuvant in the extracellular environment and augment the induction of antitumor immunity. P5 was encapsulated in cationic nanoliposomes composed of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) Cholesterol either alone or complexed with Poly (I:C). Immunocompetent BALB/c mice were immunized with the formulations 3 times in two-week intervals and the efficiency and type of immune response were then evaluated both in vitro and in vivo. The groups immunized with Lip-P5+PIC (DOTAP-Cholestrol-P5+Poly (I:C)) and Lip+PIC (DOTAP-Cholestrol+Poly (I:C)) enhanced the release of Interferon (IFN) gamma in comparison with other groups. Flow cytometry analysis revealed that Lip P5+PIC formulation induced the highest level of IFN-gamma in CD8(+) lymphocytes. Lip-P5+PIC, Lip+PIC and Lip-P5 (DOTAP-Cholestrol-P5) provided some extent of protection in terms of tumor regression in TUBO tumor mice model during the first 65days post tumor challenge but at the end only the tumors of mice immunized with Lip-P5+PIC were significantly smaller than all other groups. Furthermore, tumors of mice receiving Lip-P5+PIC grew at a significantly slower rate throughout the observation period. Our results showed that the combination of Poly (I:C) and DOTAP with the tumor antigen and without applying additional T-helper epitope induced strong antitumor responses. The observations presented here are of great interest for future vaccine studies. PMID- 27260486 TI - The Added Value of the CT Colonography Reporting and Data System. PMID- 27260487 TI - Re: Han et al. PMID- 27260488 TI - A Population-based Model of Local Control and Survival Benefit of Radiotherapy for Lung Cancer. AB - AIMS: To estimate the population-based locoregional control and overall survival benefits of radiotherapy for lung cancer if the whole population were treated according to evidence-based guidelines. These estimates were based on a published radiotherapy utilisation (RTU) model that has been used to estimate the demand and planning of radiotherapy services nationally and internationally. MATERIALS AND METHODS: The lung cancer RTU model was extended to incorporate an estimate of benefits of radiotherapy alone, and of radiotherapy in conjunction with concurrent chemotherapy (CRT). Benefits were defined as the proportional gains in locoregional control and overall survival from radiotherapy over no radiotherapy for radical indications, and from postoperative radiotherapy over surgery alone for adjuvant indications. A literature review (1990-2015) was conducted to identify benefit estimates of individual radiotherapy indications and summed to estimate the population-based gains for these outcomes. Model robustness was tested through univariate and multivariate sensitivity analyses. RESULTS: If evidence-based radiotherapy recommendations are followed for the whole lung cancer population, the model estimated that radiotherapy alone would result in a gain of 8.3% (95% confidence interval 7.4-9.2%) in 5 year locoregional control, 11.4% (10.8-12.0%) in 2 year overall survival and 4.0% (3.6-4.4%) in 5 year overall survival. For the use of CRT over radiotherapy alone, estimated benefits would be: locoregional control 1.7% (0.8-2.4%), 2 year overall survival 1.7% (0.5 2.8%) and 5 year overall survival 1.2% (0.7-1.9%). CONCLUSIONS: The model provided estimates of radiotherapy benefit that could be achieved if treatment guidelines are followed for all cancer patients. These can be used as a benchmark so that the effects of a shortfall in the utilisation of radiotherapy can be better understood and addressed. The model can be adapted to other populations with known epidemiological parameters to ensure the planning of equitable radiotherapy services. PMID- 27260489 TI - Standardized reporting of adverse events after microvascular decompression of cranial nerves; a population-based single-institution consecutive series. AB - OBJECTIVE: To investigate frequencies of adverse events occurring within 30 days after microvascular decompression (MVD) surgery using a standardized report form of adverse events. METHODS: We conducted a retrospective review of 98 adult patients (>=16 years) treated with MVD between 1 January 1994 and 1 June 2013. Adverse events occurring within 30 days were classified according to the Landriel Ibanez classification for neurosurgical complications: grade I represents any non life threatening complication treated without invasive procedures; grade II is complications requiring invasive management; grade III is life-threatening adverse events requiring treatment in an intensive care unit (ICU); grade IV is death as a result of complications. We sought to compare our results with reports from the literature. RESULTS: Patients' median age was 61 years (range 26-83), and 64 (65 %) were females. Indications for MVD were trigeminal neuralgia (n = 77, 79 %), glossopharyngeal neuralgia (n = 4, 4 %), hemifacial spasm (n = 16, 16 %) and combined trigeminal neuralgia and hemifacial spasm (n = 1, 1 %). The overall 30-day complication rate was 20 %, with 14 % grade I complications, 5 % grade II complications and 1 % grade III complications. The comparison with the literature was hampered by the diverse and unsystematic way of reporting complications. CONCLUSION: We provide a standardized report of postoperative complications in a consecutive patient series undergoing MVD. Due to the heterogeneous and non-standardized reporting of complications in the literature, it is difficult to know if our 20 % complication rate is low or high. Standardized reporting is a necessity for meaningful and more valid comparisons across studies. The safety of MVD, a fairly standardized neurosurgical procedure, is well suited for comparisons across centers provided that complications are reported in a standardized manner. PMID- 27260490 TI - Outcome following phrenic nerve transfer to musculocutaneous nerve in patients with traumatic brachial palsy: a qualitative systematic review. AB - BACKGROUND: The phrenic nerve can be transferred to the musculocutaneous nerve in patients with traumatic brachial plexus palsy in order to recover biceps strength, but the results are controversial. There is also a concern about pulmonary function after phrenic nerve transection. In this paper, we performed a qualitative systematic review, evaluating outcomes after this procedure. METHOD: A systematic review of published studies was undertaken in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. Data were extracted from the selected papers and related to: publication, study design, outcome (biceps strength in accordance with BMRC and pulmonary function) and population. Study quality was assessed using the "strengthening the reporting of observational studies in epidemiology" (STROBE) standard or the CONSORT checklist, depending on the study design. RESULTS: Seven studies were selected for this systematic review after applying inclusion and exclusion criteria. One hundred twenty-four patients completed follow-up, and most of them were graded M3 or M4 (70.1 %) for biceps strength at the final evaluation. Pulmonary function was analyzed in five studies. It was not possible to perform a statistical comparison between studies because the authors used different parameters for evaluation. Most of the patients exhibited a decrease in pulmonary function tests immediately after surgery, with recovery in the following months. Study quality was determined using STROBE in six articles, and the global score varied from 8 to 21. CONCLUSIONS: Phrenic nerve transfer to the musculocutaneous nerve can recover biceps strength >=M3 (BMRC) in most patients with traumatic brachial plexus injury. Early postoperative findings revealed that the development of pulmonary symptoms is rare, but it cannot be concluded that the procedure is safe because there is no study evaluating pulmonary function in old age. PMID- 27260492 TI - A pregnant woman with anaemia and thrombocytopenia. PMID- 27260491 TI - Low level lead exposure and pregnancy outcomes in an observational birth cohort study: dose-response relationships. AB - BACKGROUND: National and international guidelines on safe levels for blood Pb in pregnancy focus on a threshold above which exposure is of concern. However, it has recently been suggested that the decrease in birth weight per unit increase in blood Pb is actually greater at lower than at higher concentrations of Pb without evidence of a lower threshold of effect. Our aim was to investigate whether there was evidence for a differential effect of maternal Pb levels on birth outcomes and/or a threshold value for effects. METHODS: Blood samples from pregnant women enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) were analysed. Data collected on the infants included anthropometric variables. We fitted adjusted multivariable fractional polynomial models for birth outcomes. RESULTS: Adjusted models that assumed a linear relationship between untransformed blood Pb and the outcomes provided the best fit: an increase of 1 ug/dl was associated with changes in birth weight of -9.93 (95 % CI -20.27, 0.41) g, head circumference -0.03 (95 % CI -0.06, 0.00) cm and crown-heel length -0.05 (95 % CI -0.10, 0.00) cm. CONCLUSION: There was no evidence in this study to suggest a supralinear dose-response relationship or a lower threshold for the effect of maternal blood Pb on birth outcomes. This has implications for consideration of national and international guidelines on levels of concern in pregnancy. Exposure to Pb should be kept as low as possible during pregnancy to minimise adverse outcomes. PMID- 27260493 TI - In vitro evidence of the promoting effect of testosterone in kidney stone disease: A proteomics approach and functional validation. AB - Incidence of kidney stone disease in males is 2- to 4-fold greater than in females. This study aimed to determine effects of testosterone on kidney stone disease using a proteomics approach. MDCK renal tubular cells were treated with or without 20nM testosterone for 7days. Cellular proteins were extracted, resolved by 2-DE, and stained with Deep Purple fluorescence dye (n=5 gels derived from 5 independent samples/group). Spot matching, quantitative intensity analysis, and statistics revealed significant changes in levels of nine protein spots after testosterone treatment. These proteins were then identified by nanoLC ESI-Qq-TOF MS/MS. Global protein network analysis using STRING software revealed alpha-enolase as the central node of protein-protein interactions. The increased level of alpha-enolase was then confirmed by Western blotting analysis, whereas immunofluorescence study revealed the increased alpha-enolase on cell surface and intracellularly. Functional analysis confirmed the potential role of the increased alpha-enolase in enhanced calcium oxalate monohydrate (COM) crystal cell adhesion induced by testosterone. Finally, neutralization of surface alpha enolase using anti-alpha-enolase antibody successfully reduced the enhanced COM crystal-cell adhesion to the basal level. Our data provided in vitro evidence of promoting effect of testosterone on kidney stone disease via enhanced COM crystal cell adhesion by the increased surface alpha-enolase. BIOLOGICAL SIGNIFICANCE: The incidence of kidney stone disease in male is 2- to 4-fold greater than in female. One of the possible factors of the male preference is the higher testosterone hormone level. However, precise molecular mechanisms that testosterone plays in kidney stone disease remained unclear. Our present study is the first exploratory investigation on such aspect using a proteomics approach. Our data also provide a novel mechanistic aspect of how testosterone can impact the risk of kidney stone formation (i.e. the discovery that testosterone increases alpha-enolase expression on the surface of renal tubular cells that is responsible, at least in part, for crystal-cell adhesion). PMID- 27260494 TI - A multi-model statistical approach for proteomic spectral count quantitation. AB - The rapid development of mass spectrometry (MS) technologies has solidified shotgun proteomics as the most powerful analytical platform for large-scale proteome interrogation. The ability to map and determine differential expression profiles of the entire proteome is the ultimate goal of shotgun proteomics. Label free quantitation has proven to be a valid approach for discovery shotgun proteomics, especially when sample is limited. Label-free spectral count quantitation is an approach analogous to RNA sequencing whereby count data is used to determine differential expression. Here we show that statistical approaches developed to evaluate differential expression in RNA sequencing experiments can be applied to detect differential protein expression in label free discovery proteomics. This approach, termed MultiSpec, utilizes open-source statistical platforms; namely edgeR, DESeq and baySeq, to statistically select protein candidates for further investigation. Furthermore, to remove bias associated with a single statistical approach a single ranked list of differentially expressed proteins is assembled by comparing edgeR and DESeq q values directly with the false discovery rate (FDR) calculated by baySeq. This statistical approach is then extended when applied to spectral count data derived from multiple proteomic pipelines. The individual statistical results from multiple proteomic pipelines are integrated and cross-validated by means of collapsing protein groups. BIOLOGICAL SIGNIFICANCE: Spectral count data from shotgun proteomics experiments is semi-quantitative and semi-random, yet a robust way to estimate protein concentration. Tag-count approaches are routinely used to analyze RNA sequencing data sets. This approach, termed MultiSpec, utilizes multiple tag-count based statistical tests to determine differential protein expression from spectral counts. The statistical results from these tag-count approaches are combined in order to reach a final MultiSpec q-value to re-rank protein candidates. This re-ranking procedure is completed to remove bias associated with a single approach in order to better understand the true proteomic differences driving the biology in question. The MultiSpec approach can be extended to multiple proteomic pipelines. In such an instance, MultiSpec statistical results are integrated by collapsing protein groups across proteomic pipelines to provide a single ranked list of differentially expressed proteins. This integration mechanism is seamlessly integrated with the statistical analysis and provides the means to cross-validate protein inferences from multiple proteomic pipelines. PMID- 27260495 TI - Profiling the proteomics in honeybee worker brains submitted to the proboscis extension reflex. AB - : The proboscis extension reflex (PER) is an unconditioned stimulus (US) widely used to access the ability of honeybees to correlate it with a conditioned stimulus (CS) during learning and memory acquisition. However, little is known about the biochemical/genetic changes in worker honeybee brains induced by the PER alone. The present investigation profiled the proteomic complement associated with the PER to further the understanding of the major molecular transformations in the honeybee brain during the execution of a US. In the present study, a quantitative shotgun proteomic approach was employed to assign the proteomic complement of the honeybee brain. The results were analyzed under the view of protein networking for different processes involved in PER behavior. In the brains of PER-stimulated individuals, the metabolism of cyclic/heterocyclic/aromatic compounds was activated in parallel with the metabolism of nitrogenated compounds, followed by the up-regulation of carbohydrate metabolism, the proteins involved with the anatomic and cytoskeleton; the down-regulation of the anatomic development and cell differentiation in other neurons also occurred. SIGNIFICANCE: The assay of proboscis extension reflex is frequently used to access honeybees' ability to correlate an unconditioned stimulus with a conditioned stimulus (such as an odor) to establish learning and memory acquisition. The reflex behavior of proboscis extension was associated with various conditioned stimuli, and the biochemical/genetic evaluation of the changes occurring in honeybee brains under these conditions reflect the synergistic effects of both insect manipulations (training to answer to an unconditioned stimulus and training to respond to a conditioned stimulus). Little or no information is available regarding the biochemical changes stimulated by an unconditioned stimulus alone, such as the proboscis extension reflex. The present investigation characterizes the proteomic changes occurring in the brains of honeybee workers submitted to proboscis extension reflex. A series of metabolic and cellular processes were identified to be related to the reflex of an unconditioned stimulus. This strategy may be reproduced to further understand the processes of learning and memory acquisition in honeybees. PMID- 27260496 TI - Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity. AB - : Calcitonin may relieve pain by modulating central serotonin activity. Calcitonin partly reversed the hypersensitivity to pain induced by ovariectomy. This suggests that the anti-nociceptive effects of calcitonin in the treatment of osteoporosis may be mediated by alterations in neural serotonin transporter (SERT) activity. INTRODUCTION: This study used a rat model of osteoporosis to evaluate the role of the cerebral serotonin system in the anti-nociceptive effect of calcitonin, a drug used to treat post-menopausal osteoporosis. METHODS: Osteoporosis was induced in rats by ovariectomy (OVX). Rats were then randomized to the following four groups: sham operation, OVX, OVX plus calcitonin, or OVX plus alendronate. RESULTS: OVX led to alterations in bone micro-architecture; alendronate strongly reversed this effect, and calcitonin moderately reversed this effect. OVX increased hyperalgesia (determined as the time for hind paw withdrawal from a heat source); calcitonin reduced this effect, but alendronate had no effect. OVX increased the expression of c-Fos (a neuronal marker of pain) in the thalamus; calcitonin strongly reversed this effect, and alendronate moderately reversed this effect. OVX also reduced SERT but increased 5-HT1A receptor expression and activity; calcitonin aggravated this effect, but alendronate had no effect on recovery of SERT/5-HT1A activity and expression. CONCLUSIONS: Our study of a rat model of osteoporosis suggests that OVX-induced enhancement of the serotonergic system may protect against hyperalgesia. However, the anti-nociceptive effects of calcitonin in osteoporosis may be mediated by decreased neural SERT activity and increased activation of 5-HT1 receptors in the thalamus. PMID- 27260497 TI - Nature or manufacture: What should we fear most? AB - Of very ancient descent, domestication switched the outcome of natural selection to that due to human design. A widespread fancy is that man-created contraptions develop dangerously on their own because of their Promethean essence. This assumes implicitly-how difficult is it to refrain from thinking that we are the sawyers of nature!-that their crafted powers would dominate the autonomy resulting from billions of years of evolution. Yet artifice depends on the skills of its creator, so that it is when coming close to nature that danger surfaces. Invasive species are natural, and the havoc they create is here to call for some modesty in the appraisal of our endeavours. The farther away, the less dangerous. Being distant from man, engineered plants are considerably less harmful than animal constructs, especially those that are close to man and meant for medical use. This reality contrasts with popular belief. In this misconception lies the danger, magnified by the present demographic explosion of the invasive species Homo sapiens, which develops artificial environments that provide progressively less room for life to evolve. PMID- 27260498 TI - Gene therapy: Myth or reality? AB - Gene therapy has become a reality, although still a fragile one. Clinical benefit has been achieved over the last 17years in a limited number of medical conditions for which pathophysiological studies determined that they were favorable settings. They include inherited disorders of the immune system, leukodystrophies, possibly hemoglobinopathies, hemophilia B, and retinal dystrophies. Advances in the treatment of B-cell leukemias and lymphomas have also been achieved. Advances in vector development and possible usage of gene editing may lead to significant advances over the next years. PMID- 27260501 TI - Seasonal and Ageing-Depending Changes of Aquaporins 1 and 9 Expression in the Genital Tract of Buffalo Bulls (Bubalus bubalis). AB - The presence of Aquaporins 1 (AQP1) and 9 (AQP9), integral membrane water channels that facilitate rapid passive movement of water and solutes, was immunohistochemically detected in the excurrent ducts collected from sexually mature buffalo bulls of proven fertility during the mating (late autumn-winter) and non-mating (late spring to the beginning of autumn) seasons. Furthermore, the research was performed also on the epididymal cauda of a senile buffalo bull with inactive testis. Aquaporins 1 and 9 were immunolocalized at distinct levels. In the efferent ducts, AQP1 immunoreactivity was strongly evidenced at the apical surface of the non-ciliated cells and weakly along the basal membrane of the epithelial cells. The latter reactivity disappeared during the non-mating season. No AQP1 immunoreactivity was detected in the epithelium of epididymis and vas deferens, whereas AQP1 was expressed in the smooth muscle layer of the vas deferens. Aquaporin 1 was present in the blood vessels and in small nerve bundles all along the genital tract. The supranuclear zone of the epididymal principal cells was AQP9 immunoreactive, limited to the corpus and cauda regions, and vas deferens. The samples collected in the two reproductive seasons showed a weaker AQP9 immunoreactivity during the non-mating season. A typical AQP9 immunoreactivity was noticed in the old buffalo examined. The tested AQP molecules showed a different expression pattern in comparison with laboratory mammals, primates, equine, dog and cat. In addition, seasonal differences were noticed which are possibly useful in regard to the comprehension of the morphophysiology of reproduction in the bubaline species, which are still a matter of debate. PMID- 27260500 TI - Can a community health worker administered postnatal checklist increase health seeking behaviors and knowledge?: evidence from a randomized trial with a private maternity facility in Kiambu County, Kenya. AB - BACKGROUND: Since the 2009 WHO and UNICEF recommendation that women receive home based postnatal care within the first three days after birth, a growing number of low-income countries have explored integrating postnatal home visit interventions into their maternal and newborn health strategies. This randomized trial evaluates a pilot program in which community health workers (CHWs) visit or call new mothers three days after delivery in peri-urban Kiambu County, Kenya. METHODS: Participants were individually randomized to one of three groups: 1) early postnatal care three days after delivery provided in-person with a CHW using a simple checklist, 2) care provided by phone with a CHW using the same checklist, or 3) a standard of care group. Surveys were conducted ten days and nine weeks postnatal to measure outcomes related to compliance with referrals, self-reported health problems for mother and baby, care-seeking behaviors, and postnatal knowledge and practices around the recognition of danger signs, feeding, nutrition, infant care and family planning. RESULTS: The home visit administration of the checklist increased the likelihood that women recognized postnatal problems for themselves and their babies and increased the likelihood that they sought care to address those problems identified for the child. In both the home visit and mobile phone implementation of the checklist, actions taken for postnatal problems happened earlier, particularly for infants. Knowledge was found to be high across all groups, with limited evidence that the checklist impacted knowledge and postnatal practices around the recognition of danger signs, feeding, nutrition, infant care and family planning. CONCLUSION: We find evidence that CHW-administered postnatal checklists can lead to better recognition of postnatal problems and more timely care-seeking. Furthermore, our results suggest that CHWs can affordably deliver many of the benefits of postnatal checklists. TRIAL REGISTRATION: ClinicalTrials.gov NCT02104635 ; registered April 2, 2014. PMID- 27260499 TI - Managing Pediatric Pain in the Emergency Department. AB - Far more attention is now given to pain management in children in the emergency department (ED). When a child arrives, pain must be recognized and evaluated using a pain scale that is appropriate to the child's development and regularly assessed to determine whether the pain intervention was effective. At triage, both analgesics and non-pharmacological strategies, such as distraction, immobilization, and dressing should be started. For mild pain, oral ibuprofen can be administered if the child has not received it at home, whereas ibuprofen and paracetamol are suitable for moderate pain. For patients who still require pain relief, oral opioids could be considered; however, many EDs have now replaced this with intranasal fentanyl, which allows faster onset of pain relief and can be administered on arrival pending either intravenous access or definitive care. Intravenous opioids are often required for severe pain, and paracetamol or ibuprofen can still be considered for their likely opioid-sparing effects. Specific treatment should be used for patients with migraine. In children requiring intravenous access or venipuncture, non-pharmacological and pharmacological strategies to decrease pain and anxiety associated with needle punctures are mandatory. These strategies can also be used for laceration repairs and other painful procedures. Despite the gaps in knowledge, pain should be treated with the most up-to-date evidence in children seen in EDs. PMID- 27260502 TI - Rhodovulum algae sp. nov., isolated from an algal mat. AB - A reddish-brown-pigmented, phototrophic bacterium, designated strain JA877T, was isolated from a brown algae mat sample collected from Jalandhar beach, Gujarat, India. On the basis of the 16S rRNA gene sequence, strain JA877T belongs to the class Alphaproteobacteria and is closely related to the type strains Rhodovulum viride JA756T (99.0 %), Rhodovulum sulfidophilum Hansen W4T (98.9 %), Rhodovulumvisakhapatnamense JA181T (98.8 %),Rhodovulum kholense JA297T (97.5 %) and Rhodovulum salis JA746T (97.0). However, strain JA877T showed only 20-45 % relatedness with its phylogenetic neighbours and had a ?Tm between 5.8 and 7.0 degrees C. The major respiratory quinone was ubiquinone-10 (Q10), and the polar lipid profile was composed of the major components phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, two unidentified sulfolipids and five unidentified lipids. The major fatty acids were C18 : 1omega5c, C18 : 1omega7c/C18 : 1omega6c, C16 : 0 and C18 : 0. The DNA G+C content was 64.5 mol%. On the basis of 16S rRNA gene sequence analysis, physiological data, and chemotaxonomic and molecular differences, strain JA877T is significantly different from other species of the genus Rhodovulum and represents a novel species, for which the name Rhodovulum algae sp. nov. is proposed. The type strain is JA877T (=LMG 29228T= KCTC 42963T). PMID- 27260504 TI - Erratum: Computerized Performance Monitoring Systems: Learning and Living with its Limitations. PMID- 27260503 TI - Tumor volume improves the long-term prediction of biochemical recurrence-free survival after radical prostatectomy for localized prostate cancer with positive surgical margins. AB - PURPOSE: To develop a novel application evaluating the effect of tumor volume (TV) and percentage of high-grade tumor volume (%HGTV) on long-term biochemical recurrence-free survival rate (BCRFS) after radical prostatectomy (RP) in patients with pT2 PCa. METHODS: Retrospective analysis of 903 men with pT2 PCa between 1992 and 2004 at a single European tertiary care center was performed. Cox regression models identified risk factors for BCR. A nomogram was developed to predict the BCRFS at 5, 10 and 15 years after RP. Decision curve analyses were performed to identify the net increase in cases identified by the full model. RESULTS: BCR-free survival rates at 5, 10 and 15 years were 94, 90 and 86 %. In Cox regression analyses, TV, %HGTV and positive surgical margin status (SM) were independent predictors of BCR. Predictive accuracies (PA) at 5, 10 and 15 years of the base model (PSA, Gleason score, SM) were 76.8 % (95 % CI 67.9-78.2 %), 70.5 % (95 % CI 64.9-75.0 %) and 68.1 % (95 % CI 60.6-73.5 %). The full model, including TV and %HGTV, achieved 76.9, 72.4 and 70.7 %. These PA differences were statistically significant at 10 and 15 years (p < 0.001). CONCLUSIONS: TV and %HGTV could potentially serve as valuable measures to stratify patients at high risk of BCR. The use of our nomogram should be considered to counsel patients with pT2 disease and SM and to design appropriate follow-up or treatment regimens. PMID- 27260505 TI - A Novel Intra-aortic Device Designed for Coronary Blood Flow Amplification in Unrevascularizable Patients. AB - Patients with unrevascularizable coronary artery disease represent a substantial number of all patients with coronary disease. However, their therapeutic options are limited; they endure recurrent hospitalizations, a poor quality of life and prognosis. We aim to investigate a novel alternative approach to the treatment of this common medical condition by using a specialized intra-aortic device with coiling properties capable of enhancing diastolic coronary flow. Both a mathematical analysis and in vitro study presented in the current study have yielded enhanced coronary diastolic blood flow and energetic advantages. We suggest that this original approach might be implicated in severely symptomatic unrevascularizable patients. PMID- 27260507 TI - [Security agents on the front line against Ebola: roles, perceptions and knowledge in Fann Teaching Hospital, Dakar, Senegal]. AB - Security agents are on the front line when patients arrive at health facilities, giving them a potential role to play in an Ebola virus disease (EVD) outbreak. The position of security agents within health services is poorly documented. A survey was conducted to clarify their understanding of Ebola pathology, to assess their need for information and to determine their role in patient management. The survey included both qualitative and quantitative aspects. 80 security agents of the Fann teaching hospital (Dakar) completed questionnaires, and 11 were interviewed. Qualitative analysis was performed with Dedoose and the quantitative analysis using Excel. The results show that security agents' activities go beyond their mission of security and control. They are involved in informing, orienting and assisting patients and those accompanying them in the hospital. The security agents have basic knowledge of EVD, but overestimate the risk of transmission. They want to be more informed and to have access to protective material. These results suggest that these professionals should be taken into account when developing response strategies to Ebola outbreaks. Their knowledge of and protection against the disease must be strengthened. Non-health professionals working in health facilities should be trained in order to be able to relay information to the public. PMID- 27260506 TI - Budesonide ameliorates lung injury induced by large volume ventilation. AB - BACKGROUND: Ventilation-induced lung injury (VILI) is a health problem for patients with acute respiratory dysfunction syndrome. The aim of this study was to investigate the effectiveness of budesonide in treating VILI. METHODS: Twenty four rats were randomized to three groups: a ventilation group, ventilation/budesonide group, and sham group were ventilated with 30 ml/kg tidal volume or only anesthesia for 4 hor saline or budesonide airway instillation immediately after ventilation. The PaO2/FiO2and wet-to-dry weight ratios, protein concentration, neutrophil count, and neutrophil elastase levels in bronchoalveolar lavage fluid (BALF) and the levels of inflammation-related factors were examined. Histological evaluation of and apoptosis measurement inthe lung were conducted. RESULTS: Compared with that in the ventilation group, the PaO2/FiO2 ratio was significantly increased by treatment with budesonide. The lung wet-to-dry weight ratio, total protein, neutrophil elastase level, and neutrophilcount in BALF were decreased in the budesonide group. The BALF and plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, intercellular adhesion molecule (ICAM)-1, and macrophage inflammatory protein (MIP)-2 levels were decreased, whereas the IL-10 level was increased in the budesonide group. The phosphorylated nuclear factor (NF)-kBlevels in lung tissue were inhibited by budesonide. The histological changes in the lung and apoptosis were reduced by budesonide treatment. Bax, caspase-3, and cleaved caspase-3 were down-regulated, and Bcl-2 was up-regulated by budesonide. CONCLUSIONS: Budesonide ameliorated lung injury induced by large volume ventilation, likely by improving epithelial permeability, decreasing edema, inhibiting local and systemic inflammation, and reducing apoptosis in VILI. PMID- 27260508 TI - Adherence to Symptom-Based Care Guidelines for Down Syndrome. AB - To assess adherence to symptom-based studies recommended in the health supervision guidelines for Down syndrome from the American Academy of Pediatrics (AAP), 24 pediatric care sites participated in retrospective chart review. Symptom-based screening and 4 associated recommendations, including cervical spine radiograph, video swallow study, celiac study with tissue transglutaminase and sleep study were analyzed by reviewing well-child visit notes of 264 children with Down syndrome. Given trends toward symptom-based screens, Pearson's chi square test and Fisher's exact test were used to determine the association between symptom presence and receiving corresponding symptom-based screens. Adherence rates were widely variable ranging from 0% to 79% completion. Symptom based studies were performed in 22% to 36% of patients. Symptom screens were documented positive in many patients, but the presence of symptoms did not correlate with completion of symptom-based screens. Symptom-based screening is low; associated studies were performed in patients without documented symptoms contrary to AAP recommendation. PMID- 27260509 TI - Effective embryo production from Holstein cows treated with gonadotropin releasing hormone during early lactation. AB - The low efficiency of embryo production in Holstein cows during early lactation presents many challenges for animal production. To improve its efficiency, the outcomes of single GnRH injections 48 hours before each of three cycles of ovum pick up (OPU; weeks 2, 4, and 6) were compared with three cycles of unstimulated OPU (controls; weeks 1, 3, and 5) in 35 Holstein cows during 6 weeks of early lactation (40-80 days postpartum). More total follicle numbers (19.5 vs. 16.0; P < 0.05) but fewer dominant follicles (0.5 vs. 1.4; P < 0.01) were observed by ultrasound, and more cumulus-oocyte complexes were collected in a single OPU in the treatment cycles compared with controls (15.3 vs. 11.5; P < 0.05). The numbers of morphologically "good" cumulus-oocyte complexes graded A and B in the stimulated OPUs were significantly greater than in controls (2.8 vs. 1.7 and 5.8 vs. 4.2, respectively; P < 0.05). Significantly, more oocytes stained positively with brilliant cresyl blue after GnRH treatment compared with the control cycles (13.7 vs. 9.6; P < 0.05). After in vitro fertilization, embryos in the treatment cycles had improved development (P < 0.01) during each developmental stage compared with the controls (9.0 vs. 6.2 two-cell embryos; 4.7 vs. 3.0 four-cell embryos; 3.3 vs. 2.0 morulae; and 3.0 vs. 1.7 blastocysts, respectively). Moreover, there was no significant difference in pregnancy rate of the recipient cows after embryo transfer (57.1% vs. 42.1%; P > 0.05) no matter if the embryos came from the GnRH-treated cycles or not. Thus, GnRH-stimulated OPUs improved the efficiency of embryo production in Holstein cows during early lactation. This novel method for in vitro embryo production should benefit the dairy industry. PMID- 27260510 TI - Adaptations of semen characteristics and sperm motility to harsh salinity: Extreme situations encountered by the euryhaline tilapia Sarotherodon melanotheron heudelotii (Dumeril, 1859). AB - In most teleost fishes, sperm cells are quiescent in the seminal plasma and are activated by either a drop (fresh water fish) or an increase in osmolality (marine fish) when released in the water. It is most interesting to examine how the mechanisms of sperm motility activation can adapt to a broad range of salinities, as applies to some euryhaline species, and particularly to the tilapia Sarotherodon melanotheron heudelotii, which can reproduce at salinities from 0 up to 120 in the wild. Here, the gonado-somatic index, semen characteristics, and the osmotic and ionic requirements of sperm motility activation were compared in S. m. heudelotii reared in fresh water (FW), sea water (SW), or hypersaline water (HW; salinities of 0, 35, and 70, respectively). No salinity-dependent differences were found in gonado-somatic index or semen characteristics, except for an increase of seminal plasma osmolality with increasing salinity (from 318 to 349 mOsm kg(-1) in FW and HW fish, respectively). The osmolality range allowing the highest percentages of sperm activation broadened and shifted toward higher values with increasing fish ambient salinity (150-300, 300-800, and 500-1200 mOsm kg(-1), for FW, SW, and HW fish, respectively). Nevertheless, at the three fish rearing salinities, sperm could be activated in media that were hypotonic, isotonic, or hypertonic relative to the seminal plasma, at least when some calcium was present above a threshold concentration. The [Ca(2+)] required for the activation of S. m. heudelotii sperm is (1) higher in fish reared at a higher salinity (2) higher in hypertonic than that in hypotonic activation media, whatever the fish rearing salinity, and (3) higher in the presence of Na(+) or K(+), the negative effects of which increased with an increase in fish rearing salinity. The [Ca(2+)]/[Na(+)] ratios allowing for maximal sperm motility in SW or HW fish are close to those observed in natural environments, either in sea or hypersaline waters. In comparison to most teleosts with external fertilization, the total duration of sperm motility in S. m. heudelotii was exceptionally long (>2 hours regardless the fish rearing salinities). The decrease in sperm activity with increasing time since activation did not result from limiting energy reserves, as the addition of calcium in the activation medium caused most spermatozoa to become motile again. The comparison of sperm characteristics of S. m. heudelotii acclimated from FW to SW or HW with those of fish maintained all lifelong at their native salinity showed that adaptive responses were completed within 2 months or less. PMID- 27260511 TI - C-Reactive Protein Identifies Low-Risk Metabolically Healthy Obese Persons: The European Prospective Investigation of Cancer-Norfolk Prospective Population Study. AB - BACKGROUND: Conflicting data exist about the cardiovascular risk of metabolically healthy obese persons. The prognostic value of C-reactive protein (CRP) in this intriguing group is unknown. We assessed the association between CRP levels and the risk of coronary heart disease (CHD) in metabolically healthy persons with abdominal obesity. METHODS AND RESULTS: In the European Prospective Investigation of Cancer-Norfolk prospective cohort, CRP levels and information on metabolic syndrome criteria were available for 7279 participants, of whom 825 (11%) developed CHD during a follow-up period of 10.9+/-1.8 years. There was a trend toward a higher multivariable-adjusted hazard ratio for CHD in metabolically healthy obese participants with CRP levels >2 mg/L compared with <2 mg/L (hazard ratio 1.59, 95% CI 0.97-2.62, P=0.066). Metabolically unhealthy obese participants had significantly higher CHD risk compared with metabolically healthy obese participants with CRP levels <2 mg/L (hazard ratio 1.88, 95% CI 1.20-2.94, P=0.006). Most important, we found that the risk of CHD among metabolically healthy obese persons with CRP levels <2 mg/L was comparable to that of metabolically healthy nonobese persons (hazard ratio 0.91, 95% CI 0.60 1.39, P=0.674). CONCLUSIONS: Among metabolically healthy obese persons, low CRP levels were associated with a CHD risk comparable to that of metabolically healthy nonobese persons. CRP appears to be an easy and widely available method for identifying a low-risk subpopulation among metabolically healthy obese persons. PMID- 27260513 TI - 8-Oxo-7,8-dihydro-2'-deoxyguanosine and other lesions along the coding strand of the exon 5 of the tumour suppressor gene P53 in a breast cancer case-control study. AB - The next-generation sequencing studies of breast cancer have reported that the tumour suppressor P53 (TP53) gene is mutated in more than 40% of the tumours. We studied the levels of oxidative lesions, including 8-oxo-7,8-dihydro-2' deoxyguanosine (8-oxodG), along the coding strand of the exon 5 in breast cancer patients as well as in a reactive oxygen species (ROS)-attacked breast cancer cell line using the ligation-mediated polymerase chain reaction technique. We detected a significant 'in vitro' generation of 8-oxodG between the codons 163 and 175, corresponding to a TP53 region with high mutation prevalence, after treatment with xanthine plus xanthine oxidase, a ROS-generating system. Then, we evaluated the occurrence of oxidative lesions in the DNA-binding domain of the TP53 in the core needle biopsies of 113 of women undergoing breast investigation for diagnostic purpose. An increment of oxidative damage at the -G- residues into the codons 163 and 175 was found in the cancer cases as compared to the controls. We found significant associations with the pathological stage and the histological grade of tumours. As the major news of this study, this largest analysis of genomic footprinting of oxidative lesions at the TP53 sequence level to date provided a first roadmap describing the signatures of oxidative lesions in human breast cancer. Our results provide evidence that the generation of oxidative lesions at single nucleotide resolution is not an event highly stochastic, but causes a characteristic pattern of DNA lesions at the site of mutations in the TP53, suggesting causal relationship between oxidative DNA adducts and breast cancer. PMID- 27260512 TI - Selection for reduced translation costs at the intronic 5' end in fungi. AB - It is generally believed that introns are not translated; therefore, the potential intronic features that may be related to the translation step (occurring after splicing) have yet to be thoroughly studied. Here, focusing on four fungi, we performed for the first time a comprehensive study aimed at characterizing how translation efficiency is encoded in introns and affects their evolution. By analysing their intronome we provide evidence of selection for STOP codons close to the intronic 5' end, and show that the beginning of introns are selected for significantly high translation, presumably to reduce translation and metabolic costs in cases of non-spliced introns. Ribosomal profiling data analysis in Saccharomyces cerevisiae supports the conjecture that in this organism intron retention frequently occurs, introns are partially translated, and their translation efficiency affects organismal fitness. We show that the reported results are more significant in highly translated and highly spliced genes, but are not associated only with genes with a specific function. We also discuss the potential relation of the reported signals to efficient nonsense mediated decay due to splicing errors. These new discoveries are supported by population-genetics considerations. In addition, they are contributory steps towards a broader understanding of intron evolution and the effect of silent mutations on gene expression and organismal fitness. PMID- 27260514 TI - GenFamClust: an accurate, synteny-aware and reliable homology inference algorithm. AB - BACKGROUND: Homology inference is pivotal to evolutionary biology and is primarily based on significant sequence similarity, which, in general, is a good indicator of homology. Algorithms have also been designed to utilize conservation in gene order as an indication of homologous regions. We have developed GenFamClust, a method based on quantification of both gene order conservation and sequence similarity. RESULTS: In this study, we validate GenFamClust by comparing it to well known homology inference algorithms on a synthetic dataset. We applied several popular clustering algorithms on homologs inferred by GenFamClust and other algorithms on a metazoan dataset and studied the outcomes. Accuracy, similarity, dependence, and other characteristics were investigated for gene families yielded by the clustering algorithms. GenFamClust was also applied to genes from a set of complete fungal genomes and gene families were inferred using clustering. The resulting gene families were compared with a manually curated gold standard of pillars from the Yeast Gene Order Browser. We found that the gene-order component of GenFamClust is simple, yet biologically realistic, and captures local synteny information for homologs. CONCLUSIONS: The study shows that GenFamClust is a more accurate, informed, and comprehensive pipeline to infer homologs and gene families than other commonly used homology and gene family inference methods. PMID- 27260515 TI - The effects of sleep restriction and altered sleep timing on energy intake and energy expenditure. AB - Experimental evidence suggests that sleep restriction increases energy intake (EI) and may alter energy expenditure (EE). However, it is unknown whether the timing of a sleep restriction period impacts EI and EE the following day. Hence, we examined the effects of sleep restriction with an advanced wake-time or delayed bedtime on next day EI and EE. Twelve men and 6 women (age: 23+/-4years, body fat: 18.8+/-10.1%) participated in 3 randomized crossover sessions: control (habitual bed- and wake-times), 50% sleep restriction with an advanced wake-time and 50% sleep restriction with a delayed bedtime. Outcome variables included sleep architecture (polysomnography), EI (food menu), total EE and activity times (accelerometry). Carbohydrate intake was greater on day 2 in the delayed bedtime vs. control session (1386+/-513 vs. 1579+/-571kcal; P=0.03). Relative moderate intensity physical activity (PA) time was greater in the delayed bedtime session vs. control and advanced wake-time sessions on day 1 (26.6+/-19.9 vs. 16.1+/-10.6 and 17.5+/-11.8%; P=0.01), whereas vigorous-intensity PA time was greater following advanced wake-time vs. delayed bedtime on day 1 (2.7+/-3.0 vs. 1.3+/ 2.4%; P=0.004). Greater stage 1 sleep (beta=110kcal, 95% CI for beta=42 to 177kcal; P=0.004), and a trend for lower REM sleep (beta=-20kcal, 95% CI for beta=-41 to 2kcal; P=0.07), durations were associated with greater EI between sleep restriction sessions. These findings suggest that the timing of a sleep restriction period impacts energy balance parameters. Additional studies are needed to corroborate these findings, given the increasing prevalence of shift workers and incidences of sleep disorders and voluntary sleep restriction. PMID- 27260516 TI - Individual differences in saccharin acceptance predict rats' food intake. AB - Following previous results indicating that low acceptance of saccharin-sweetened yoghurt was associated with slower weight gain, the aim of this experiment was to determine which of three measures of individual differences would predict subsequent chow consumption, body weight gain, and fat mass. Pre-test measures consisted of amount of running in an activity wheel, amount of 0.1% saccharin solution consumed over 24h, and performance on an elevated plus maze (EPM). Rats were then maintained for three weeks on a diet of standard chow and water. Subsequent post-testing repeated the procedures used in pre-testing. The rats were then culled and fat pads excised and weighed. Pre-testing revealed a negative correlation between saccharin acceptance and activity, while neither measure correlated with anxiety in the EPM. Pre-test saccharin acceptance was positively correlated with subsequent chow consumption, percent weight gain, and g/kg fat mass. Multiple regression analyses including all three pre-test measures confirmed saccharin acceptance as a predictor of chow consumption and, marginally, of fat pad mass, while high anxiety predicted low percent body weight gain. PMID- 27260517 TI - Tumor Boards from the Perspective of Ambulant Oncological Care. AB - BACKGROUND: Cancer therapy requires the cooperation of physicians from different disciplines. At the core of the collaboration are 'tumor boards' (also known as 'multidisciplinary team meetings' and 'tumor conferences'). However, there is limited health care research that addresses the multiple facets of such meetings. MATERIAL AND METHODS: Data were analyzed from 3 routinely conducted surveys comprising information from (i) office-based hematologists and oncologists, (ii) their patients, and (iii) quality indicators. RESULTS: Most office-based oncologists stated that they participate in tumor boards taking place in hospitals. Although tumor boards are viewed as time intensive and lack financial compensation, they are considered as beneficial for patient care. Less than half of patients knew that their cases were discussed at a tumor board; those who knew rated the collaboration between their treating doctors as more positive, but also experienced slightly higher distress levels. The quality indicators showed that tumor board meetings were documented in three-quarters of the patient charts, but only half included the tumor board's recommendation. CONCLUSIONS: Participation in tumor boards is perceived as beneficial by oncologists and not just considered as a fulfillment of societies' recommendations or guidelines. The higher distress levels in patients who knew that their case was discussed at a tumor board may have occurred because more difficult cases are discussed at tumor boards and since the oncologists spend more time explaining the therapy process in complex cases, including the tumor board results. PMID- 27260518 TI - Serous carcinoma arising from uterine adenomyosis/adenomyotic cyst of the cervical stump: a report of 3 cases. AB - BACKGROUND: Serous carcinoma arising in adenomyosis and adenomyotic cyst is very rare. Only 3 serous carcinomas and 5 serous endometrial intraepithelial carcinomas (EIC) have been reported to date. METHODS: We reviewed the clinicopathological features of 2 serous carcinoma in uterine adenomyosis and 1 serous EIC in adenomyotic cyst of the cervical stump. RESULTS: Case 1 had an endometrial serous carcinoma in the uterine myometrium and the left ovary. A minor component of benign endometrial glands with minimal endometrial stroma was found in the uterine mass and the surrounding myometrium. Case 2 showed 3 small foci of serous carcinoma, serous EIC and endometrial glandular dysplasia (EmGD) in the adenomyosis. Scanty serous carcinoma was present in the endometrium without evidence of myometrial invasion. The eutopic endometrium in both case 1 and 2 had no evidence of neoplastic changes after complete examination. Case 3 had 3 microscopic serous EICs in the adenomyotic cysts of the cervical stump. One EIC lesion coexisted with EmGD. No cancer was found in the endocervical tube although the preoperative endocervical biopsy showed a poorly differentiated endometrioid carcinoma. Immunohistochemistry demonstrated that serous carcinoma in case 1 and EIC in all 3 cases showed a characteristic pattern of p53 and p16 over expression, high Ki67 index, and lack of WT1, ER and PR staining. EmGD in case 1 and 3 had a similar staining pattern except a lower Ki67 index and the presence of ER expression. CONCLUSIONS: We believe that this case series may expand our recognition on serous carcinoma arising in uterine adenomyosis/adenomyotic cyst including extra-uterine spread and the potential synchronous growth of carcinomas in eutopic endometrium. PMID- 27260519 TI - Effect of Voriconazole on Candida tropicalis Biofilms: Relation with ERG Genes Expression. AB - Candida tropicalis has emerged as the third most prevalent fungal pathogens and its ability to form biofilms has been considered one of the most important virulence factors, since biofilms represent high tolerance to antifungal agents. However, the mechanisms of C. tropicalis biofilm resistance to antifungals remain poorly understood. Thus, the main aim of this work was to infer about the effect of voriconazole on the formation and control of C. tropicalis biofilms and disclose its relationship with ERG genes' expression. Planktonic cells tolerance of several C. tropicalis clinical isolates to voriconazole was determined through of antifungal susceptibility test, and the effect of this azole against C. tropicalis biofilm formation and pre-formed biofilms was evaluated by cultivable cells determination and total biomass quantification. ERG genes expression was analyzed by quantitative real-time polymerase chain reaction. This work showed that C. tropicalis resistance to voriconazole is strain dependent and that voriconazole was able to partially control biofilm formation, but was unable to eradicate C. tropicalis pre-formed biofilms. Moreover, C. tropicalis biofilms resistance to voriconazole seems to be associated with alterations of sterol content in the cell membrane, resulting in ERG genes overexpression. Voriconazole is unable to control C. tropicalis biofilms, and the overexpression of ERG genes is a possible mechanism of biofilm resistance. PMID- 27260520 TI - TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. AB - PURPOSE: In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions. METHODS: We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14 according to the EORTC criteria on FDG-PET imaging had better rates of 2-year OS than did non-responders (36.4 % vs. 8.3 %, P = 0.015). CONCLUSIONS: TLG-S criteria may be of greater help in predicting survival outcomes than other forms of assessment. Bone flares, which can interfere with the interpretation of treatment response based on PERCIST criteria, are not uncommon in patients with metastatic lung adenocarcinoma treated with erlotinib. PMID- 27260521 TI - Radiation dosimetry of (68)Ga-PSMA-11 (HBED-CC) and preliminary evaluation of optimal imaging timing. AB - PURPOSE: The clinical introduction of (68)Ga-PSMA-11 ("HBED-CC") ligand targeting the prostate-specific membrane antigen (PSMA) has been regarded as a significant step forward in the diagnosis of prostate cancer (PCa). In this study, we provide human dosimetry and data on optimal timing of PET imaging after injection. METHODS: Four patients with recurrent PCa were referred for (68)Ga-PSMA-11 PET/CT. Whole-body PET/CTlow-dose scans were conducted at 5 min, and 1, 2, 3, 4 and 5 h after injection of 152-198 MBq (68)Ga-PSMA-11. Organs of moderate to high uptake were used as source organs; their total activity was determined at all measured time points. Time-activity curves were created for each source organ as well as for the remainder. The radiation exposure of a (68)Ga-PSMA-11 PET was identified using the OLINDA-EXM software. In addition, tracer uptake was measured in 16 sites of metastases. RESULTS: The highest tracer uptake was observed in the kidneys, liver, upper large intestine, and the urinary bladder. Mean organ doses were: kidneys 0.262 +/- 0.098 mGy/MBq, liver 0.031 +/- 0.004 mGy/MBq, upper large intestine 0.054 +/- 0.041 mGy/MBq, urinary bladder 0.13 +/- 0.059 mGy/MBq. The calculated mean effective dose was 0.023 +/- 0.004 mSv/MBq (=0.085 +/- 0.015 rem/mCi). Most tumor lesions (n = 16) were visible at 3 h p.i., while at all other time points many were not qualitatively present (10/16 visible at 1 h p.i.). CONCLUSIONS: The mean effective dose of a (68)Ga-PSMA-11 PET is 0.023 mSv/MBq. A 3-h delay after injection was optimal timing for (68)Ga-PSMA-11 PET/CT in this patient cohort. PMID- 27260522 TI - One registration multi-atlas-based pseudo-CT generation for attenuation correction in PET/MRI. AB - PURPOSE: The outcome of a detailed assessment of various strategies for atlas based whole-body bone segmentation from magnetic resonance imaging (MRI) was exploited to select the optimal parameters and setting, with the aim of proposing a novel one-registration multi-atlas (ORMA) pseudo-CT generation approach. METHODS: The proposed approach consists of only one online registration between the target and reference images, regardless of the number of atlas images (N), while for the remaining atlas images, the pre-computed transformation matrices to the reference image are used to align them to the target image. The performance characteristics of the proposed method were evaluated and compared with conventional atlas-based attenuation map generation strategies (direct registration of the entire atlas images followed by voxel-wise weighting (VWW) and arithmetic averaging atlas fusion). To this end, four different positron emission tomography (PET) attenuation maps were generated via arithmetic averaging and VWW scheme using both direct registration and ORMA approaches as well as the 3-class attenuation map obtained from the Philips Ingenuity TF PET/MRI scanner commonly used in the clinical setting. The evaluation was performed based on the accuracy of extracted whole-body bones by the different attenuation maps and by quantitative analysis of resulting PET images compared to CT-based attenuation-corrected PET images serving as reference. RESULTS: The comparison of validation metrics regarding the accuracy of extracted bone using the different techniques demonstrated the superiority of the VWW atlas fusion algorithm achieving a Dice similarity measure of 0.82 +/- 0.04 compared to arithmetic averaging atlas fusion (0.60 +/- 0.02), which uses conventional direct registration. Application of the ORMA approach modestly compromised the accuracy, yielding a Dice similarity measure of 0.76 +/- 0.05 for ORMA-VWW and 0.55 +/- 0.03 for ORMA-averaging. The results of quantitative PET analysis followed the same trend with less significant differences in terms of SUV bias, whereas massive improvements were observed compared to PET images corrected for attenuation using the 3-class attenuation map. The maximum absolute bias achieved by VWW and VWW-ORMA methods was 06.4 +/- 5.5 in the lung and 07.9 +/- 4.8 in the bone, respectively. CONCLUSIONS: The proposed algorithm is capable of generating decent attenuation maps. The quantitative analysis revealed a good correlation between PET images corrected for attenuation using the proposed pseudo-CT generation approach and the corresponding CT images. The computational time is reduced by a factor of 1/N at the expense of a modest decrease in quantitative accuracy, thus allowing us to achieve a reasonable compromise between computing time and quantitative performance. PMID- 27260523 TI - Phoma herbarum, a soil fungus able to grow on natural lignin and synthetic lignin (DHP) as sole carbon source and cause lignin degradation. AB - The fungus Phoma herbarum isolated from soil showed growth on highly pure lignin extracted from spruce wood and on synthetic lignin (DHP). The lignin remaining after cultivation was shown to have a lower molecular weight. The reduction in the numbers of ether linkages of the extracted lignins was also observed by derivatization followed by reductive cleavage (DFRC) in combination with (31)P NMR studies. The fungal strain showed an ability to degrade synthetic lignin by extracellular catalysts. GC-MS was applied to study the evolution of low molar mass adducts, e.g., monolignols and it was shown that a reduced coniferyl alcohol product was produced from DHP in a cell-free environment. The work has demonstrated the ability of soil microbes to grow on lignin as sole carbon source. The potential impact is in the production of low molar mass renewable phenols for material application. PMID- 27260524 TI - Engineered biosynthesis of biodegradable polymers. AB - Advances in science and technology have resulted in the rapid development of biobased plastics and the major drivers for this expansion are rising environmental concerns of plastic pollution and the depletion of fossil-fuels. This paper presents a broad view on the recent developments of three promising biobased plastics, polylactic acid (PLA), polyhydroxyalkanoate (PHA) and polybutylene succinate (PBS), well known for their biodegradability. The article discusses the natural and recombinant host organisms used for fermentative production of monomers, alternative carbon feedstocks that have been used to lower production cost, different metabolic engineering strategies used to improve product titers, various fermentation technologies employed to increase productivities and finally, the different downstream processes used for recovery and purification of the monomers and polymers. PMID- 27260525 TI - Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma. AB - INTRODUCTION: Reports of improved survival in patients with pathologic complete response (pCR) to neoadjuvant therapy for esophageal and gastroesophageal junction (GEJ) adenocarcinoma is extrapolated from heterogeneous studies that include squamous cell histology. We sought to determine if pCR is associated with a survival advantage in a homogenous group of patients with esophageal adenocarcinoma. METHODS: This is a single institution analysis of all patients with T2-T4 or node positive esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy and esophagectomy between 2004 and 2014. Patients were divided into two groups based on pathological response, pCR vs. incomplete pathological response (iPR). Survival outcomes were evaluated using standard Kaplan-Meier methods and multivariable Cox regression models. RESULTS: A total of 205 patients were included in the study: 38 (19 %) patients with pCR and 167 patients (81 %) with iPR. The two groups were similar with respect to clinical stage, age, gender, comorbid conditions, ECOG status, smoking, and alcohol use. Patients in the pCR group had a higher percentage of tumors located in middle third of esophagus (11 vs. 2 %, p = 0.04) while tumor grade was similar in both groups. Median follow-up was 50 months, range 2-109 months. The 3-year overall (OS) and recurrence-free survival (RFS) for iPR was 48 and 39 %, respectively, vs. 86 and 80 % for pCR group, respectively. CONCLUSION: This analysis of a cohort of homogeneous patients with esophageal adenocarcinoma undergoing multimodality therapy showed that pCR is an independent predictor of improved RFS and OS. This data contributes to a growing body of evidence highlighting the benefits of neoadjuvant therapy specific to esophageal adenocarcinoma particularly when pCR is achieved. PMID- 27260526 TI - Choledochal Cyst Disease in a Western Center: A 30-Year Experience. AB - BACKGROUND: The aim of this study was to report a Western experience in the diagnosis and management of choledochal cyst disease. RESULTS: Sixty-seven patients were identified including 15 children and 52 adults; 76.1 % were females. The median age at diagnosis was 3 [inter-quartile range (IQR) = 6.0-0.7] years for children, and 46 [IQR = 55.6-34.3] years for adults. Forty-eight patients (72 %) were symptomatic. Types of choledochal cyst included: I (n = 49, 73.1 %), II (n = 1, 1.5 %), IV (n = 9, 13.4 %), and V (n = 8, 12 %). The median diameter of the type I choledochal cyst was 35 [IQR = 47-25] mm. All 48 patients underwent excision of cyst with Roux-en-Y hepaticojejunostomy, and eight underwent resection with hepaticoduodenostomy. Six patients underwent liver resection, and five patients underwent orthotopic liver transplantation. Malignancy was concomitant in five adult patients, being identified on preoperative imaging in three cases; and atypia was seen in three additional patients. Early morbidity included Clavien-Dindo classification grades III (n = 7) and II (n = 5), while long-term complications consisted of Clavien-Dindo grades V (n = 5), IV (n = 2), III (n = 18), and II (n = 1). CONCLUSIONS: Presentation and management of choledochal cyst is varied. Malignant transformation is often detected incidentally, and so should be the driving source for resection when a choledochal cyst is diagnosed. PMID- 27260527 TI - Quality Sleep Is Associated With Overnight Metabolic Rate in Healthy Older Adults. AB - Background : Increasing age is associated with an increase in overnight metabolic rate. Objective : To determine the relationship between quality sleep, sleep efficiency, and overnight metabolic rate as measured in a respiration chamber in older participants. Methods : The study design was cross sectional. Forty participants, aged 50 to 83 years (17 males, age 63+/-7 years, body mass index 25.7+/-2.3kg/m2) spent one night in a respiration chamber to measure sleep stages by polysomnography and overnight metabolic rate (OMR). Data were collected between 23:00 and 07:00. Subsequently basal metabolic rate (BMR) was measured under a ventilated hood. Quality sleep was calculated as time spent in rapid-eye movement (REM) sleep and slow wave sleep divided by total sleep time, and sleep efficiency was calculated as total sleep time divided by the sleep period time. Body movement was measured between 23:00 and 07:00 with an accelerometer on the wrist. Overnight metabolic rate was adjusted for body size by dividing by basal metabolic rate (OMR/BMR). Results : OMR/BMR was positively associated with age (r = 0.48, p < .001), and quality sleep was negatively associated with age (r = 0.51, p < .001). The variance of OMR/BMR was significantly explained by quality sleep (r = -0.58, p < 0.001). Body movement was negatively related to sleep efficiency (r = -0.38, p<0.01) with no effect on OMR/BMR. When OMR/BMR was adjusted for quality sleep, the effect of age was non significant. Conclusion : Quality sleep is inversely associated with the age-related rise in overnight metabolic rate, suggesting that increased overnight metabolic rate is a biological sign of ageing as a consequence of diminished quality sleep. PMID- 27260529 TI - Trace metal distributions in the sediments of the Little Akaki River, Addis Ababa, Ethiopia. AB - The levels and distribution of trace metals (Cr, Mn, Co, Ni, Cu, Zn, Cd and Pb) at eleven water and sediment stations on the Little Akaki River (LAR) in Addis Ababa, Ethiopia, were determined. The binding forms of the metals in various geochemical fractions of the sediments were also quantified. The molar ratio of the sum of the simultaneously extractable metals (?SEM) and acid-volatile sulphide (AVS)-as a measure for predicting metal-induced toxicity-was estimated. LAR trace levels in water for Cu, Zn, and, particularly Mn were, in most instances, higher than the recommended guidelines for healthy aquatic ecosystems. Total trace metal (TTM) contents in the LAR sediments at certain stations exceeded "threshold effect concentrations" and even "probable effect concentrations", especially in the cases of Zn, Cu, Ni, Pb, and at all stations for Mn. This became more apparent after applying "normalizations" to the relatively lower TTM adsorption capacities of coarse-grained, organic-poor sediments. Sequential extraction of the sediments showed that trace metals generally have a higher affinity for Fe-Mn oxide and organic matter/sulphidic fractions, followed by the residual fraction. Mn was relatively strongly bound to the exchangeable, carbonate bound fractions, whereas a large proportion of Cr was found in the residual fraction. The Sigma[SEM]/[AVS] ratio pointed to potential metal-induced toxicity of sediments collected from seven out of the eleven stations. The results indicate that trace metal pollution pose risks to the health of ecosystems, and to human communities that use the river for a range of different purposes. PMID- 27260528 TI - Multidrug-resistant Enterobacteriaceae from indoor air of an urban wastewater treatment plant. AB - Wastewater treatment plants (WWTPs) have been recognized as sources of bioaerosols that may act as vehicles for dissemination of pathogens and multidrug resistant (MDR) bacteria. The occurrence of MDR Enterobacteriaceae in indoor air of an urban WWTP was investigated. A possible airborne contamination with extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacteriaceae was also explored. Fourteen of 39 Enterobacteriaceae isolates were MDR. These isolates were found at all sampling sites, mainly at the secondary sedimentation settings. The highest levels of resistance were detected in three different species: Enterobacter cloacae, Escherichia coli, and Citrobacter freundii. Furthermore, one of the airborne E. coli isolates was phenotypically characterized as an ESBL producer. Additionally, five isolates showed non-susceptibility to at least one carbapenem tested. The presence of genes encoding relevant beta-lactamase types in these ESBL-producing and carbapenem-resistant Enterobacteriaceae isolates was investigated by PCR. Results showed amplification for bla CTX-M and bla OXA. These findings are relevant both in terms of occupational/public health and of environmental dissemination of MDR bacteria. PMID- 27260531 TI - Erratum to: 'Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis'. PMID- 27260530 TI - Selective withdrawal optimization in river-reservoir systems; trade-offs between maximum allowable receiving waste load and water quality criteria enhancement. AB - In this paper, a new systematic approach is designed to maximize the demand coverage and receiving waste load by river-reservoir systems while enhancing water quality criteria. The approach intends to control the reservoir eutrophication while developing a trade-off between the maximum receiving load and shortage on demand coverage. To simulate the system, a hybrid process-based and data-driven model is tailored. Initially, the two-dimensional hydrodynamics and water quality simulation model (CE-QUAL-W2) is linked with an effective single and/or multiple optimization algorithms (PSO) to evaluate the proposed scenarios. To increase the computational efficiencies, the simulation model is substituted with a surrogate model (ANN) in an adaptive-dynamically refined routine. The proposed method is illustrated by a case study in Iran, namely, Karkheh River Reservoir, for 180-monthly periods. The results showed the applicability of the methodology especially to solve high-dimensional multi period complex water resource optimization problems. Also, the results demonstrated that eutrophication could be reduced under the optimal inflow phosphate control and reservoir operation, regulating the total phosphorous concentration in the reservoir. PMID- 27260532 TI - Aluminum Trichloride Inhibits the Rat Osteoblasts Mineralization In Vitro. AB - Aluminum (Al) is an accumulative toxic metal. Excessive Al accumulation inhibits osteoblasts mineralization and induces osteoporosis. However, the inhibition mechanism of Al on the mineralization is not fully understood. Thus, in this study, the rat osteoblasts were cultured and exposed to 0 mmol L-1 (control group, CG) and 0.52 mmol L-1 aluminum trichloride (AlCl3, treatment group, TG) for 7, 14, and 21 days, respectively. We found that mineralized matrix nodules, the activity of bone alkaline phosphatase, the concentration of extracellular calcium, the mRNA expression of type-I collagen, the mRNA and protein expressions of osteopontin, osteocalcin, and bone sialoprotein were all decreased, while the concentration of extracellular phosphorus was increased in TG compared with CG with time prolonged. Taken together, these results indicated that AlCl3 inhibited osteoblasts mineralization in vitro. PMID- 27260533 TI - Promotive Effect of Zinc Ions on the Vitality, Migration, and Osteogenic Differentiation of Human Dental Pulp Cells. AB - Zinc is an essential trace element for proper cellular function and bone formation. However, its exact role in the osteogenic differentiation of human dental pulp cells (hDPCs) has not been fully clarified before. Here, we speculated that zinc may be effective to regulate their growth and osteogenic differentiation properties. To test this hypothesis, different concentrations (1 * 10-5, 4 * 10-5, and 8 * 10-5 M) of zinc ions (Zn2+) were added to the basic growth culture medium and osteogenic inductive medium. Cell viability and migration were measured by cell counting kit-8 (CCK-8) and transwell migration assay in the basic growth culture medium, respectively. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expression levels of selective osteogenic differentiation markers and zinc transporters. Alkaline phosphatase (ALP) activity analysis and alizarin red S staining were used to investigate the mineralization of hDPCs. Exposure of hDPCs to Zn2+ stimulated their viability and migration capacity in a dose- and time dependent manner. RT-qPCR assay revealed elevated expression levels of osteogenic differentiation-related genes and zinc transporters genes in various degrees. ALP activity was also increased with elevated Zn2+ concentrations and extended culture periods, but enhanced matrix nodules formation were observed only in 4 * 10-5 and 8 * 10-5 M Zn2+ groups. These findings suggest that specific concentrations of Zn2+ could potentiate the vitality, migration, and osteogenic differentiation of hDPCs. We may combine optimum zinc element into pulp capping materials to improve their biological performance. PMID- 27260534 TI - Effect of Molybdenum Nanoparticles on Blood Cells, Liver Enzymes, and Sexual Hormones in Male Rats. AB - Despite an increasing surge in application of nanoparticles in industries, there is a serious lack of information concerning their impact on human health and the environment. The present study investigated effects of molybdenum nanoparticles (Mo NPs) injected intraperitoneally into Sprague-Dawley rats at different doses of Mo NPs (5, 10, and 15 mg/kg BW per day) during a period of 28 days. Hematological and biochemical parameters as well as sexual hormones and histopathological examinations of the liver and testis were assessed and compared with control group. The results showed that the serum levels of testosterone decreased significantly in both groups of 10 and 15 mg (Mo NPs)/kg BW in comparison with the control group (p < 0.05). However, there were insignificant differences observed in luteinizing hormone (LH) levels and hematological parameters when compared with the control group (p > 0.05). The results of liver enzymes showed that serum levels of aspartate aminotransferase (AST) decreased significantly in both dosage groups of 5 and 10 mg/kg BW (Mo NPs) when compared with the control group (p < 0.05), and significant decrease obtained in lactate dehydrogenase (LDH) levels at dose of 5 mg/kg BW in comparison with the control group (p < 0.05). The histopathological examination of testis showed a decrease in number of Leydig cells. Also, the number of chronic inflammatory cells increased in portal triad and parenchyma in liver tissue of rats exposed to Mo NPs. PMID- 27260535 TI - Facial flat warts in a young patient with a previous trauma: an example of isotraumatopic response. PMID- 27260536 TI - Analysis of the coding-complete genomic sequence of groundnut ringspot virus suggests a common ancestor with tomato chlorotic spot virus. AB - Groundnut ringspot virus (GRSV) and tomato chlorotic spot virus (TCSV) share biological and serological properties, so their identification is carried out by molecular methods. Their genomes consist of three segmented RNAs: L, M and S. The finding of a reassortant between these two viruses may complicate correct virus identification and requires the characterization of the complete genome. Therefore, we present for the first time the complete sequences of all the genes encoded by a GRSV isolate. The high level of sequence similarity between GRSV and TCSV (over 90 % identity) observed in the genes and proteins encoded in the M RNA support previous results indicating that these viruses probably have a common ancestor. PMID- 27260547 TI - Decreased baroreflex sensitivity is linked to the atherogenic index, retrograde inflammation, and oxidative stress in subclinical hypothyroidism. AB - : Purpose/aim of the study: The present study investigated the link of hyperlipidemia, inflammation and oxidative stress (OS) to cardiovascular (CV) risks in subclinical hypothyroidism (SCH). MATERIALS AND METHODS: We enrolled 81 subclinical hypothyroid patients and 80 healthy subjects as control. Their CV and autonomic functions were assessed by spectral analysis of heart rate variability (HRV), continuous blood pressure variability (BPV) measurement and conventional autonomic function testing. Thyroid profile, lipid profile, immunological, inflammatory and OS markers were estimated and correlated with the baro-reflex sensitivity (BRS), the marker of sympathovagal imbalance (SVI) & CV risk. RESULTS: Mean arterial pressure (MAP, P<0.0001), total peripheral resistance (TPR, P<0.0001), ratio of low-frequency to high-frequency power of HRV (LF-HF ratio) (P<0.0001) were significantly higher and BRS (P<0.0001) was significantly lower in SCH group than the control group. BRS significantly correlated with heart rate, MAP, LF-HF ratio, lipid risk factors, anti-thyroperoxidase antibody, thyroid-stimulating hormone, high-sensitive C-reactive protein (hsCRP), malondialdehyde (MDA) and SCH. CONCLUSIONS: It was concluded that SVI is associated with SCH. Though dyslipidemia, inflammation and OS contributed to decreased BRS, SCH per se contributed maximally to it. Decreased BRS could be a physiological basis of increased CV risks in patients with SCH. PMID- 27260548 TI - Effects of Climate and Climate Change on Vectors and Vector-Borne Diseases: Ticks Are Different. AB - There has been considerable debate as to whether global risk from vector-borne diseases will be impacted by climate change. This has focussed on important mosquito-borne diseases that are transmitted by the vectors from infected to uninfected humans. However, this debate has mostly ignored the biological diversity of vectors and vector-borne diseases. Here, we review how climate and climate change may impact those most divergent of arthropod disease vector groups: multivoltine insects and hard-bodied (ixodid) ticks. We contrast features of the life cycles and behaviour of these arthropods, and how weather, climate, and climate change may have very different impacts on the spatiotemporal occurrence and abundance of vectors, and the pathogens they transmit. PMID- 27260549 TI - Late postpartum HELLP syndrome over 10 days after delivery. PMID- 27260550 TI - The Orthopedic Literature 2015. PMID- 27260551 TI - Efficacy of loop diuretics in the management of undocumented patients with end stage renal disease. AB - An estimated 6000 patients who are undocumented immigrants have end-stage renal disease (ESRD) and routinely present to public safety-net hospitals for life saving emergent dialysis treatments. Because these patients lack a dialysis unit, they often do not have access to medication management consistently coordinated by a nephrologist, and this can result in more frequent emergency department (ED) utilization and cost of care. We hypothesized that patients who were taking loop diuretics had fewer ED visits for emergency dialysis. Loop diuretics can potentially take advantage of residual renal function and mitigate excess fluid gain that can induce heart failure and high potassium, the two most common indications for emergency dialysis. In our univariable analysis, patients on furosemide had 3.1 fewer ED visits on average compared with patients who are not on furosemide. After adjusting for vintage and serum potassium measures, the average number of ED visits was about 1.1 visits less in furosemide-treated patients compared with patients not receiving furosemide (95% confidence interval, -4.4 to 2.1). These results suggest that loop diuretics may have an important role in undocumented patients with ESRD with residual renal function. Further study to develop practical approaches to the care of undocumented patients with ESRD is greatly needed. PMID- 27260552 TI - Shared decision making in the ED: ethical considerations. AB - The process of shared decision making (SDM) is an ethical imperative in the physician-patient relationship, especially in the emergency department (ED), where SDM can present unique challenges because patients and emergency physicians often have no established relationship and decisions about diagnosis, treatment, and disposition are time dependent. SDM should be guided by the ethical principles of autonomy, beneficence, nonmaleficence, and justice and the related principle of stewardship of finite resources. The objective of this article is to outline the ethical considerations of SDM in the ED in the context of diagnostic evaluations, therapeutic interventions, disposition decisions, and conflict resolution and to explore strategies for reaching decision consensus. Several cases are presented to highlight the ethical principles in SDM in the ED. SDM is an important approach to diagnostic testing in the ED. Achieving agreement regarding diagnostic evaluations requires a balance of respect for patient autonomy and stewardship of resources. SDM regarding ED therapeutic interventions is an important component of the balance of respect for patient autonomy and beneficence. While respecting patient autonomy, emergency physicians also recognize the importance of the application of professional judgment to achieve the best possible outcome for patients. SDM as an ethical imperative in the context of ED disposition is especially important because of the frequent ambiguity of equipoise in these situations. Unique clinical situations such as pediatric patients or patients who lack decisional capacity merit special consideration. PMID- 27260553 TI - Survival after profound acidosis and rhabdomyolysis due to dietary supplement use. PMID- 27260554 TI - Posttraumatic retroclival subarachnoid hemorrhage: what to do in an emergency? PMID- 27260555 TI - Emergent radiation therapy as definite airway management for dyspnea with mediastinal mass. PMID- 27260556 TI - Fresh frozen plasma is permissive for systemic inflammatory response syndrome, infection, and sepsis in multiple-injured patients. AB - BACKGROUND: The correction of coagulopathy with fresh frozen plasma (FFP) is one of the main issues in the treatment of multiple-injured patients. Infectious and septic complications contribute to an adverse outcome in multiple-injured patients. Here, we investigated the role of FFP in the development of inflammatory complications given within the first 48 hours. METHODS: A total of 2033 patients with multiple injuries and an Injury Severity Score greater than 16 points and aged 16 years or older were included. The population was subdivided into 2 groups: those who received FFP and those who did not. The data were analyzed using SPSS version 22.0. Associations between the data were tested using Pearson correlation. Independent predictivity was analyzed by binary logistic regression and multivariate regression. Data were considered as significant if P<.05. RESULTS: The prothrombin time at admission was significantly lower (68.5%+/-23.3% vs 81.8%+/-21.0% normal; P<.001) in the group receiving FFP. The application of FFP led to a more severe systemic inflammatory response syndrome (SIRS) grade (3.0+/-1.2 vs 2.2+/-1.4; P<.001), to a higher infection rate (48% vs 28%; P<.001), and to a higher sepsis rate (29% vs 13%; P<.001) in the patients receiving FFP. The correlations between SIRS and the incidence of infections and sepsis increased with the amount of FFP applied (P<.001). CONCLUSIONS: Treatment with FFP of bleeding patients with multiple injuries enhances the risk of SIRS, infection, and sepsis; however, a multifactorial genesis has to be postulated. PMID- 27260557 TI - Assessment of the LifeVac, an anti-choking device, on a human cadaver with complete airway obstruction. PMID- 27260558 TI - Retroorbital optic nerve cysticercosis. PMID- 27260559 TI - Noninvasive Failure Load Prediction of Vertebrae with Simulated Lytic Defects and Biomaterial Augmentation. AB - The spine is the most common site for secondary bone metastases, and clinical management for fractures is based on size and geometry of the defect. About 75% of the bone needs to be damaged before lesions are detectable, so clinical tools should measure changes in both geometry and material properties. We have developed an automated, user-friendly, Spine Cancer Assessment (SCA) image-based analysis method that builds on a platform designed for clinical practice providing failure characteristics of vertebrae. The objectives of this study were to (1) validate SCA predictions with experimental failure load outcomes; (2) evaluate the planning capabilities for prophylactic vertebroplasty procedures; and (3) investigate the effect of computed tomography (CT) protocols on predicted failure loads. Twenty-one vertebrae were randomly divided into two groups: (1) simulated defect without treatment (negative control) [n = 9] and (2) with treatment [n = 12]. Defects were created and a polymeric biomaterial was injected into the vertebrae in the treated-defect group. Spines were scanned, reconstructed with two algorithms, and analyzed for fracture loads. To virtually plan for prophylactic intervention, vertebrae with empty lesions were simulated to be augmented with either poly(methyl methacrylate) (PMMA) or a novel bone replacement copolymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)]. Axial rigidities were calculated from the CT images. Failure loads, determined from the cross section with the lowest axial rigidity, were compared with experimental values. Predicted loads correlated well with experimental outcomes (R(2) = 0.73, p < 0.0001). Predictions from negative control specimens highly correlated with measured values (R(2) = 0.90, p < 0.0001). Although a similar correlation was obtained using both algorithms, the smooth reconstruction (B30) tended to underestimate predicted failure loads by ~50% compared with the ~10% underestimate of the sharp reconstruction (B70). Percent increase in failure loads after virtual vertebroplasty showed a higher increase in samples with PMMA compared with those with copolymer. The SCA method developed in this study calculated failure loads from quantitative computed tomography scans in vertebrae with simulated metastatic lytic defects, with or without treatment, facilitating clinical applicability and providing more reliable guidelines for physicians to select appropriate treatment options. Furthermore, the analysis could accommodate augmentation planning procedures that aimed to determine the optimum material that would increase vertebral body failure load. PMID- 27260560 TI - Early pregnancy thyroid hormone reference ranges in Chilean women: the influence of body mass index. AB - OBJECTIVE: Thyroid dysfunction and obesity during pregnancy have been associated with negative neonatal and obstetric outcomes. Thyroid hormone reference ranges have not been established for the pregnant Hispanic population. This study defines thyroid hormone reference ranges during early pregnancy in Chilean women and evaluates associations of body mass index (BMI) with thyroid function. DESIGN, PATIENTS, MEASUREMENTS: This is a prospective observational study of 720 healthy Chilean women attending their first prenatal consultation at an outpatient clinic. Thyroid function [TSH, Free T4, Total T4 and antithyroid peroxidase antibodies (TPOAb)] and BMI were assessed at 8.8 +/- 2.4 weeks of gestational age. RESULTS: Median, 2.5th percentile (p2.5), and 97.5th percentile (p97.5) TSH values were higher, while median, p2.5, and p97.5 free T4 values were lower in obese patients compared with normal weight patients. Obesity was associated with a median TSH 16% higher (P = 0.035) and a median free T4 6.5% lower (P < 0.01) than values from patients with normal weight. BMI had a small, but statistically significant effect on TSH (P = 0.04) and free T4 (P < 0.01) when adjusted by maternal age, TPO antibodies, parity, sex of the newborn, gestational age and smoking. In all TPOAb (-) patients, median (p2.5-p.97.5) TSH was 1.96 mIU/l (0.11-5.96 mIU/l) and median (p2.5-p.97.5) free T4 was 14.54 pmol/l (11.1 - 19.02 pmol/l). Applying these reference limits, we found a prevalence of overt and subclinical hypothyroidism of 0.9% and 3.05% respectively. CONCLUSIONS: TSH distributes at higher values and free T4 at lower values in obese pregnant women compared to normal weight pregnant women. Thyroid hormone reference ranges derived from Chilean patients with negative TPOAb are different from the fixed internationally proposed reference ranges and may be used in the Hispanic population. PMID- 27260562 TI - Single-Fraction Spine Stereotactic Body Radiation Therapy for the Treatment of Chordoma. AB - PURPOSE: Chordoma is a radioresistant tumor that presents a therapeutic challenge with spine involvement, as high doses of radiation are needed for local control while limiting dose to the spinal cord. The purpose of this study is to determine the efficacy and safety of single-fraction spine stereotactic body radiation therapy for the treatment of spine chordoma. METHODS: A retrospective review of our institutional database from 2006 to 2013 identified 8 patients (12 cases) with chordoma of the spine who were treated with spine stereotactic body radiation therapy. Surgical resection was performed in 7 of the 12 cases. The treatment volume was defined by the bony vertebral level of the tumor along with soft tissue extension appreciated on magnetic resonance imaging fusion. Medical records and imaging were assessed for pain relief and local control. Treatment toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Median age was 59 years (range, 17-91). Median target volume was 48 cm3 (1-304), and median prescription dose was 16 Gy (11-16). Median conformality index was 1.44 (1.14-3.21), and homogeneity index was 1.12 (1.05 1.19). With a median follow-up time of 9.7 months (.5-84), local control was achieved in 75% of the cases treated. One patient developed limited grade 2 spinal cord myelopathy that resolved with steroids. There were no other treatment toxicities from spine stereotactic body radiation therapy. CONCLUSION: Single fraction spine stereotactic body radiation therapy can be safely delivered to treat chordoma of the spine with the potential to improve pain symptoms. Although the early data are suggestive, long-term follow-up with more patients is necessary to determine the efficacy of spine stereotactic body radiation therapy in the treatment of chordoma of the spine. PMID- 27260563 TI - US seeks to reduce sodium consumption by one third. PMID- 27260565 TI - The Creation of a Pediatric Hospital Medicine Dashboard: Performance Assessment for Improvement. AB - BACKGROUND AND OBJECTIVES: Leaders of pediatric hospital medicine (PHM) recommended a clinical dashboard to monitor clinical practice and make improvements. To date, however, no programs report implementing a dashboard including the proposed broad range of metrics across multiple sites. We sought to (1) develop and populate a clinical dashboard to demonstrate productivity, quality, group sustainability, and value added for an academic division of PHM across 4 inpatient sites; (2) share dashboard data with division members and administrations to improve performance and guide program development; and (3) revise the dashboard to optimize its utility. METHODS: Division members proposed a dashboard based on PHM recommendations. We assessed feasibility of data collection and defined and modified metrics to enable collection of comparable data across sites. We gathered data and shared the results with division members and administrations. RESULTS: We collected quarterly and annual data from October 2011 to September 2013. We found comparable metrics across all sites for descriptive, productivity, group sustainability, and value-added domains; only 72% of all quality metrics were tracked in a comparable fashion. After sharing the data, we saw increased timeliness of nursery discharges and an increase in hospital committee participation and grant funding. CONCLUSIONS: PHM dashboards have the potential to guide program development, mobilize faculty to improve care, and demonstrate program value to stakeholders. Dashboard implementation at other institutions and data sharing across sites may help to better define and strengthen the field of PHM by creating benchmarks and help improve the quality of pediatric hospital care. PMID- 27260566 TI - Small female rib cage fracture in frontal sled tests. AB - OBJECTIVES: The 2 objectives of this study are to (1) examine the rib and sternal fractures sustained by small stature elderly females in simulated frontal crashes and (2) determine how the findings are characterized by prior knowledge and field data. METHODS: A test series was conducted to evaluate the response of 5 elderly (average age 76 years) female postmortem human subjects (PMHS), similar in mass and size to a 5th percentile female, in 30 km/h frontal sled tests. The subjects were restrained on a rigid planar seat by bilateral rigid knee bolsters, pelvic blocks, and a custom force-limited 3-point shoulder and lap belt. Posttest subject injury assessment included identifying rib cage fractures by means of a radiologist read of a posttest computed tomography (CT) and an autopsy. The data from a motion capture camera system were processed to provide chest deflection, defined as the movement of the sternum relative to the spine at the level of T8. A complementary field data investigation involved querying the NASS-CDS database over the years 1997-2012. The targeted cases involved belted front seat small female passenger vehicle occupants over 40 years old who were injured in 25 to 35 km/h delta-V frontal crashes (11 to 1 o'clock). RESULTS: Peak upper shoulder belt tension averaged 1,970 N (SD = 140 N) in the sled tests. For all subjects, the peak x-axis deflection was recorded at the sternum with an average of -44.5 mm or 25% of chest depth. The thoracic injury severity based on the number and distribution of rib fractures yielded 4 subjects coded as Abbreviated Injury Scale (AIS) 3 (serious) and one as AIS 5 (critical). The NASS-CDS field data investigation of small females identified 205 occupants who met the search criteria. Rib fractures were reported for 2.7% of the female occupants. CONCLUSIONS: The small elderly test subjects sustained a higher number of rib cage fractures than expected in what was intended to be a minimally injurious frontal crash test condition. Neither field studies nor prior laboratory frontal sled tests conducted with 50th percentile male PMHS predicted the injury severity observed. Although this was a limited study, the results justify further exploration of the risk of rib cage injury for small elderly female occupants. PMID- 27260561 TI - Energetic interventions for healthspan and resiliency with aging. AB - Several behavioral and pharmacological strategies improve longevity, which is indicative of delayed organismal aging, with the most effective interventions extending both life- and healthspan. In free living creatures, maintaining health and function into old age requires resilience against a multitude of stressors. Conversely, in experimental settings, conventional housing of rodents limits exposure to such challenges, thereby obscuring an accurate assessment of resilience. Caloric restriction (CR) and exercise, as well as pharmacologic strategies (resveratrol, rapamycin, metformin, senolytics), are well established to improve indices of health and aging, but some paradoxical effects have been observed on resilience. For instance, CR potently retards the onset of age related diseases, and improves lifespan to a greater extent than exercise in a variety of models. However, exercise has proven more consistently beneficial to organismal resilience against a broad array of stressors, including infections, surgery, wound healing and frailty. CR can improve cellular stress defenses and protect from frailty, but also impairs the response to infections, bed rest and healing. How an intervention will impact not only longevity, health and function, but also resiliency, is critical to better understanding translational implications. Thus, organismal robustness represents a critical, albeit understudied aspect of aging, which needs more careful attention in order to better inform on how putative age-delaying strategies will impact preservation of health and function in response to stressors with aging in humans. PMID- 27260567 TI - Seroprevalence of Leishmania infection and molecular detection of Leishmania tropica and Leishmania infantum in stray cats of Izmir, Turkey. AB - Leishmaniasis caused by more than 20 species of genus Leishmania is transmitted by the bite of infected phlebotomine sand flies. The studies on Leishmania infection in cats is very few in Turkey and therefore we aimed to screen stray cats living in city of Izmir located in western Turkey using nested PCR targeting kinetoplast DNA and serological techniques (ELISA and IFA). Leishmania DNA positive samples were also studied by ITS1 real time PCR. Whole blood and serum samples were obtained from stray cats (n: 1101) living in different counties of Izmir. In serological assays, a serum sample was considered positive in 1:40 dilution in IFA and for ELISA a serum sample was accepted positive when the absorbance value (AV) exceeded the mean AV + Standard Deviation (SD) of the negative control serum samples. According to the results, the seropositivity rates were 10.8% (119/1101) and 15.2% (167/1101) by in house ELISA and IFA, respectively. Among serology coherent samples, the seropositivity rate was 11.1% (116/1047) as detected by both assays after discordant samples (n: 54) were discarded. Of the 1101 stray cats, six (0.54%) were positive by nested PCR while only one of these six samples was positive by ITS1 real time PCR. During PCR, three controls designated as Leishmania infantum, Leishmania tropica, and Leishmania major were used for species identification. According to nested PCR results, L. tropica was identified in two cats (no.76 and 95). In another cat (no. 269), there were two bands in which one of them was well-matched with L. infantum and the other band had ~850 bp size which does not match with any controls. Remaining three cats (no. 86, 514, and 622) also had the ~850 bp atypical band size. ITS1 real time PCR detected L. tropica in only one cat (no. 622) which showed an atypical band size in nested PCR. These results indicated that three cats with only one atypical band (no. 86, 514, and 622) and the cat with mixed infection (no. 269) were infected with L. tropica. Altogether, L. tropica was detected in all six DNA positive cats and L. infantum was detected in one cat with mixed infection. In conclusion, although the reservoir role of cats in nature is still unclear the high seroprevalence rate against Leishmania parasites and detecting parasite DNA in stray cats in Izmir indicates that the stray cats are frequently bitten by infected sand flies. Further research activities are required to reveal the frequency of leishmaniasis in cats in different regions of Turkey where Leishmania species are endemic. PMID- 27260568 TI - Ethnobotanical knowledge on botanical repellents employed in the African region against mosquito vectors - A review. AB - Mosquitoes (Diptera: Culicidae) represent a huge threat for millions of humans and animals worldwide, since they act as vectors for important parasites and pathogens, including malaria, filariasis and important arboviruses, such as dengue, West Nile and Zika virus. No vaccines or other specific treatments are available against the arboviruses transmitted by mosquitoes, and avoidance of mosquito bites remains the best strategy. African regions are usually hit most whose inhabitants are poor, and the use of repellent plants is the only efficient protection against vectors they have. Ethnobotanical knowledge of such plants and their use is usually passed on orally from one generation to another. However, it is also important to preserve this information in a written form, as well. Ethnobotanical research projects carried out in the regions of today's Ethiopia, South Africa, Nigeria, Kenya, and Tanzania indicate that the native inhabitants of the African study regions traditionally use 64 plant species, belonging to 30 families. Aromatic plants (i.e., Citrus spp., Eucalyptus spp., Lantana camara, Ocimum spp. and Lippia javanica) the most commonly used in all the study regions. Native people know three major methods of using repellent plants: (i) production of repellent smoke from burning plants, (ii) hanging plants inside the house or sprinkling leaves on the floor, (iii) the use of plant oils, juices from crushed fresh parts of the plants, or various prepared extracts applied on uncovered body parts. Overall, this review covers studies conducted only in a limited part of the African continent, highlighting the importance to undertake further research efforts to preserve the unique knowledge and traditions of the native tribes. PMID- 27260569 TI - Ankyloglossia superior syndrome: Case report and updated literature review. AB - Ankyloglossia superior (palatoglossal adhesion) is an extremely rare congenital condition with only 14 previously reported cases. When found in conjunction with other congenital abnormalities, such as cleft palate, gastrointestinal malformations, and limb malformations, this anomaly is considered part of ankyloglossia superior syndrome. We present a case of a newborn female found to have ankyloglossia superior syndrome. Surgical repair is also described. We review the available literature and discuss theories regarding the etiology of ankyloglossia superior syndrome. Clinicians should have a high degree of suspicion for other congenital anomalies when a neonate is found to have ankyloglossia superior. PMID- 27260570 TI - Swallowing dynamics status post caustic ingestion in a pediatric patient: A multidisciplinary case report. AB - A case report of a 10 year old male illustrates the effect of damage to the tongue base, hypopharynx, cricopharyngeus, and esophagus on the sensory and motor components of the swallowing mechanism. The characteristics of the dysphagia were manifested clinically, radiographically, and endoscopically. A myectomy was required to restore functional swallowing as scar tissue formation in the cricopharyngeus severely interfered with the dynamic components of swallowing. A collaborative approach facilitated communication and effective treatment planning; the multidisciplinary components in the management of this case are discussed. PMID- 27260571 TI - The effects of the antioxidant alpha-tocopherol succinate on cisplatin-induced ototoxicity in HEI-OC1 auditory cells. AB - CONCLUSION: D-alpha-tocopherol succinate significantly reduced a cisplatin induced hair cell loss in HEI-OC1 cell lines. These effects were mediated by its scavenging activity against reactive oxygen species (ROS) and inhibition of apoptosis. OBJECTIVES: Alpha-tocopherol is a class of methylated phenols, known as fat-soluble antioxidants, and is a different form of vitamin E, which reduces free radicals and acts as an antioxidant. We hypothesized that the antioxidative effect of alpha-tocopherol could protect against cisplastin-induced cytotoxicity, and thus evaluated its effects on cisplatin-induced ototoxicity in HEI-OC1 auditory cells. METHODS: HEI-OC1 cells were pretreated with D-alpha-tocopherol succinate at a concentration of 10 uM for 24 h, and then exposed to 15 uM cisplatin for 48 h. The cellular viability was measured by using the 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The intracellular ROS level was measured by using a fluorescent dye, 2',7' dichlorofluorescein diacetate (DCFH-DA). Both Annexin V-FITC and propidium iodide (PI) staining were performed to analyze the pattern of apoptosis. The enzymatic activity of caspase-3 was assayed with caspase3/CPP32 fluorometric assay kit. Also, it was assessed by immunoblotting technique of poly-ADP-ribose polymerase (PARP). RESULTS: Pretreatment with 10 uM D-alpha-tocopherol succinate protected HEI-OC1 auditory cells against cisplatin-induced cytotoxicity. D-alpha-tocopherol succinate significantly reduced the cisplatin-induced increase in ROS. D-alpha tocopherol succinate treatment induced a 15% reduction of ROS and 50% decrease in necrosis and late apoptosis as compared to cisplatin treatment. D-alpha tocopherol succinate also decreased the activation of caspase-3 and reduced levels of cleaved poly-ADP-ribose polymerase (PARP). PMID- 27260572 TI - Residual volume in the cuff of the endotracheal tube when the pilot balloon is torn off instead of deflated using a syringe. AB - BACKGROUND: In recent years, there has been a shift in airway management with the use of cuffed endotracheal tubes (ETT) in pediatric patients. While the use of a syringe to deflate the cuff is generally recommended, anecdotal observations suggest that some healthcare practitioners tear off the pilot balloon from ETT to deflate the cuff. This study was conducted to estimate the residual volume in the cuff when the pilot balloon is torn off for deflation. METHOD: The in vitro study was conducted in three phases. In phases 1 and 2, various sized cuffed ETTs (3.0, 4.0, and 5.0 mm) were inflated to achieve an intracuff pressure of 20-30 cmH2O in open atmosphere (phase 1) or inside a tube to simulate external pressure from the tracheal wall (phase 2). The pilot balloons were ripped off and the residual volume in the cuff was measured. The process was repeated using 10 ETTs of each of the 3 sizes. In phase 3, the same process was repeated using ten, size 7.0 cuffed ETTs inflated in an intubating mannequin. RESULTS: In phase 1, the percentage of the remaining residual volume was 60.7, 72.8, and 69.5% in 3.0, 4.0, and 5.0 mm ETTs respectively. Although the percentage of residual volume in phases 2 and 3 was less than phase 1, the residual volume in phases 2 and 3 still averaged approximately 60-70% of the volume required for cuff inflation. In one case, the pilot balloon tube was completely occluded and the residual volume in the cuff could not be expelled even with external pressure. CONCLUSION: Since significant percentage of the volume remained in the cuff after tearing off the pilot balloon tube with one being completely occluded, we would not recommend this method for cuff deflation. PMID- 27260573 TI - Doxycycline: A sclerosant agent to treat a case of recurrent thyroglossal duct cyst. AB - Thyroglossal duct cyst (TGDC) is one of the most common congenital anterior midline neck masses in children. Sistrunk operation is considered as the cornerstone in TGDC removal. Nevertheless, 5% to 7 % of patients have been reported to show a recurrence even after adequate resection. This necessitates at times multiple resections with potential complications. One interesting emerging technique is sclerotherapy of TGDC remnants post resection. We present here a case of a child who had a successfully treated recurrent TGDC using sclerotherapy with doxycycline. PMID- 27260574 TI - Cognitive functions in preschool children with specific language impairment. AB - OBJECTIVE: A growing body of research has focused on executive functions in children with specific language impairment (SLI). However, results show limited convergence, particularly in preschool age. The current neuropsychological study compared performance of cognitive functions focused on executive components and working memory in preschool children with SLI to typically developing controls. METHOD: Performance on the measures cognitive flexibility, inhibition, processing speed and phonological short-term memory was assessed. The monolingual, Caucasian study sample consisted of 30 children with SLI (Mage = 63.3 months, SD = 4.3 months) and 30 healthy controls (Mage = 62.2 months, SD = 3.7 months). Groups were matched for age and nonverbal IQ. Socioeconomic status of the participating families was included. RESULTS: Children with SLI had significantly poorer abilities of phonological short-term memory than matched controls. A tendency of poorer abilities in the SLI group was found for inhibition and processing speed. CONCLUSIONS: We confirmed phonological short-term memory to be a reliable marker of SLI in preschoolers. Our results do not give definite support for impaired executive function in SLI, possibly owing to limited sensitivity of test instruments in this age group. We argue for a standardization of executive function tests for research use. PMID- 27260575 TI - Mutations in eight small DFNB genes are not a frequent cause of non-syndromic hereditary hearing loss in Czech patients. AB - OBJECTIVES: To evaluate the contribution of eight small NSHL-AR (non-syndromic deafness, autosomal recessive) genes to hereditary hearing loss in Czech patients. PATIENTS AND METHODS: Unrelated Czech patients, adults and children, diagnosed with pre-lingual hereditary hearing loss with at least one similarly affected deaf sibling and with previously excluded mutations in the GJB2 gene were investigated by Sanger sequencing of the selected eight small NSHL-AR associated genes (CABP2 - 51 patients, CIB2 - 45 patients, PJVK/DFNB59 - 53 patients, GJB3 - 46 patients, ILDR1 - 48 patients, LHFPL5 - 66 patients, LRTOMT - 60 patients, TMIE - 64 patients). RESULTS: Mutations were detected in the LHFPL5 (DFNB67) gene. The patient is heterozygote for two already described pathogenic variants (p.Tyr127Cys, p.Thr165Met). In five samples, five rare heterozygous variants (two novel) predicted as pathogenic were detected in genes CABP2, ILDR1, LHFPL5 and LRTOMT. CONCLUSION: Mutations in eight small NSHL-AR genes are not a frequent cause of hereditary hearing loss in the Czech Republic. This diagnostic approach permitted the clarification of HL in only one patient - two heterozygous mutations were detected in LHFPL5 gene for the first time in Central Europe. As the use of panel base MPS certainly improves the diagnostic yield, future studies should rather profit from that diagnostic strategy. PMID- 27260576 TI - Long-term outcomes of cruciate marsupialization of intra-nasal cysts in patients with congenital dacryocele. AB - OBJECTIVES: To evaluate the long-term outcomes of cruciate marsupialization of intranasal cysts associated with congenital dacryocele. METHODS: This is a retrospective review of 15 patients of dacryoceles with intranasal cysts who underwent cruciate marsupialization of the medial wall of the cyst. Post operative follow up for a minimum of 9 months was an inclusion criterion for analysis. Data analyzed include demographics, clinical presentations, previous interventions, associated systemic abnormalities, clinical course following marsupialization and recurrences. Primary outcome measures were resolution of the dacryocele and symptomatic relief from epiphora. RESULTS: The mean age at presentation was 1.6 months with a female preponderance (60%). History of prematurity (pre-term) was noted in 20% (3/15). Swelling in the lacrimal sac area (dacryocele) was the universal presentation. Five patients (33.3%) had a prior conservative treatment. Four patients (26.6%) had respiratory distress with feeding. Acute dacryocystitis was noted in 26.6% (4/15). At a mean follow up of 19.1 months, successful outcomes were achieved in 86.6%. CONCLUSION: Cruciate marsupialization of intranasal cysts achieves good results in patients with congenital dacryocele, which are maintained over a long period of time. Early diagnosis and management may prevent acute dacryocystitis in these patients. PMID- 27260577 TI - Reliability of the reflux finding score for infants in flexible versus rigid laryngoscopy. AB - OBJECTIVES: The Reflux Finding Score for Infants (RFS-I) was developed to assess signs of laryngopharyngeal reflux (LPR) in infants. With flexible laryngoscopy, moderate inter- and highly variable intraobserver reliability was found. We hypothesized that the use of rigid laryngoscopy would increase reliability and therefore evaluated the reliability of the RFS-I for flexible versus rigid laryngoscopy in infants. METHODS: We established a set of videos of consecutively performed flexible and rigid laryngoscopies in infants. The RFS-I was scored twice by 4 otorhinolaryngologists, 2 otorhinolaryngology fellows, and 2 inexperienced observers. Cohen's and Fleiss' kappas (k) were calculated for categorical data and the intraclass correlation coefficient (ICC) was calculated for ordinal data. RESULTS: The study set consisted of laryngoscopic videos of 30 infants (median age 7.5 (0-19.8) months). Overall interobserver reliability of the RFS-I was moderate for both flexible (ICC = 0.60, 95% CI 0.44-0.76) and rigid (ICC = 0.42, 95% CI 0.26-0.62) laryngoscopy. There were no significant differences in reliability of overall RFS-I scores and individual RFS-I items for flexible versus rigid laryngoscopy. Intraobserver reliability of the total RFS-I score ranged from fair to excellent for both flexible (ICC = 0.33-0.93) and rigid (ICC = 0.39-0.86) laryngoscopies. Comparing RFS-I results for flexible versus rigid laryngoscopy per observer, reliability ranged from no to substantial (k = 0.16-0.63, mean k = 0.22), with an observed agreement of 0.08-0.35. CONCLUSION: Reliability of the RFS-I was moderate and did not differ between flexible and rigid laryngoscopies. The RFS-I is not suitable to detect signs or to guide treatment of LPR in infants, neither with flexible nor with rigid laryngoscopy. PMID- 27260578 TI - Overview of a public health approach to pediatric hearing impairment in the Pacific Islands. AB - BACKGROUND: Childhood hearing impairment is a significant cause of disability in developing countries. Otitis media and meningitis are leading infectious causes of preventable hearing loss in children. It is estimated that the Pacific Islands have among the greatest global burden of childhood hearing impairment due to infectious causes, and yet there is currently very little in the research literature on pediatric hearing disorders in this region. OBJECTIVES: (1) To review existing research literature on pediatric hearing impairment in the Pacific Islands, and (2) to present a public health approach to the development and improvement of childhood hearing services in the Pacific Islands. DATA: The primary tool was a comprehensive literature review. MEDLINE and ScienceDirect databases were searched for relevant journal articles. There was no limit on the date of publication. Any article reporting on hearing impairment in the Pacific Region was included. RESULTS: A total of 23 journal articles were found that satisfied the above inclusion criteria. The limited information available in the literature suggests that otitis media and vaccine-preventable infections are a significant cause of avoidable childhood hearing impairment in the Pacific Islands. Pediatric audiology services are limited in this region. Further research is required to develop effective public health programs that should reduce the burden of preventable childhood hearing loss in the Pacific Islands. CONCLUSIONS: There is limited information in the research literature on pediatric hearing impairment and audiology services in the Pacific Islands. Epidemiological data based on the WHO Ear and Hearing Disorders Survey Protocol are urgently needed, and the development of audiology services within the existing public and primary health care framework should reduce the burden of preventable hearing loss in the Pacific Islands. PMID- 27260579 TI - The effect of mouth breathing on exercise induced fall in lung function in children with allergic asthma and rhinitis. AB - OBJECTIVES: Exercise induced bronchospasm (EIB) represents a common feature of childhood asthma which is most commonly revealed during free running. On the other hand aerobic exercise shows significant beneficial effects in asthmatics especially on the reduction of the level of systemic inflammation and is recommended as part of its treatment. The aim of this study was to test how mandatory mouth breathing influences the exercise induced level of decrease in lung function according to the level of severity of allergic rhinitis (AR). METHODS: Free 6-minute running test preceded and followed by spirometry done with and without a nose clip a day apart was conducted in 55 children with moderate persistent asthma and AR. Children were divided into two groups according to the severity of nasal symptoms. RESULTS: There was a greater fall in forced expiratory volume in one second after exercise with a nose clip in children with less nasal symptoms than in children with more nasal symptoms (mean +/- SD; -5.28 (7.91) vs. -0.08 (4.58), p = 0.0228) compared to testing without the nose clip (mean +/- SD; LNS, -1.31 +/- 3.89%, p = 0.2408; MNS, -1.47 +/- 3.68%, p = 0.2883). CONCLUSION: Our results show that regular mouth breathing due to nasal congestion may lessen the degree of EIB in patients with persistent AR and allergic asthma. PMID- 27260580 TI - Asymptomatic Group A Streptococcus carriage in children with recurrent tonsillitis and tonsillar hypertrophy. AB - BACKGROUND: Group A Streptococcus (GAS) is the most important bacterial cause of acute tonsillitis in children. Some children are chronic GAS carriers, and this carriage is poorly understood. We determined the frequency of GAS detection using a rapid antigen detection test in pediatric patients with indications for tonsillectomy due to adenotonsillar hypertrophy or recurrent GAS infections. METHODS: Seventy-two patients underwent a tonsil swab for a rapid antigen detection test. RESULTS: The GAS rapid antigen detection test was positive in 18.1% of children. GAS was not associated with sex, age or previous history of recurrent tonsillitis. Also, the prevalence of GAS was similar between patients with either recurrent tonsillitis or tonsil hypertrophy. CONCLUSION: In our study, the GAS carriage rate was similar to other reports, and GAS carrier state was not correlated with recurrent tonsillitis. PMID- 27260581 TI - Orbital complications associated with paranasal sinus infections - A 10-year experience in Israel. AB - OBJECTIVE: Orbital involvement is the most common complication of sinus infections. The epidemiology of the disease is continuously changing in the antibiotic era. MATERIALS AND METHODS: Data on patients who were hospitalized due to acute sinusitis and orbital complications were retrospectively collected and analyzed from four medical centers in Israel during the years 2002-2012. RESULTS: 288 patients were included in the study, the average age was 14.4 years, 180 were males, and 220 were children. No significant annual increase in the number of patients was noted. The lowest number of patients was found during the summer 19.4%. A linear direct correlation was found between older age and prolonged hospital stay. Children were presented with a significantly higher Chandler score than adults. No patient had cavernous sinus thrombosis. 101 (35%) patients received antibiotics before hospital admission. Their average hospital stay was similar to those who were not treated prior to admission. 106 patients (39.8%) had fever. A direct correlation was found between older age and the presence of fever. 102 (35.4%) patients had leukocytosis. The difference in white blood cell count between patients younger than two years of age to the other groups was statistically significant. Forty four (15.3%) patients underwent surgical intervention. A direct correlation was found between leukocytosis and older age to surgery. CONCLUSIONS: Periorbital cellulitis occurs mainly in children and males and is less frequent in the summer. Children tend to have worse orbital involvement with lower temperatures than adults. Older age and leukocytosis are associated with surgical intervention. PMID- 27260582 TI - Diverse etiologies manifesting auditory neuropathy characteristics from infants with profound hearing loss and clinical implications. AB - OBJECTIVE: Auditory neuropathy spectrum disorder (ANSD) is a hearing disorder with impaired signal transmission from the inner ear to the brain. The electrophysiological characteristics of auditory neuropathy (AN characteristics) are marked with presence of otoacoustic emissions (OAE) or cochlear microphonics (CM) in the absence of auditory brainstem response (ABR). This study aimed to review etiologies related to AN characteristics from infants with profound hearing loss (HL), either unilaterally or bilaterally. STUDY DESIGN: Prospective cohort study for thirty infants with prelingual profound HL. METHODS: ABR, OAE, and/or CM were analyzed to identify electrophysiological characteristics. Temporal bone computed tomography and/or internal acoustic canal magnetic resonance imaging were reviewed to identify anatomical abnormalities. The electrophysiological characteristics and cochlear nerve status were analyzed according to the laterality of deafness (unilateral vs bilateral). RESULTS: Among the total 41 ears (from 30 infants) with profound HL, 13 ears (7 (36.8%) of 19 ears with unilateral HL and 6 (27.3%) of 22 ears associated with bilateral HL) showed AN characteristics (37.1%), and 21 ears showed cochlear nerve deficiency (CND) (51.2%). AN characteristics was detected about two times more frequently in cases with CND (38.1%) than with anatomically normal cochlear nerve (20.0%), the difference not reaching a statistical significance probably due to a small sample size. Detection of AN characteristics did not differ between unilateral and bilateral profound HL, even though presence of CND was more frequently detected in cases with unilateral profound HL than with bilateral cases. There were at least five types of etiologies related to AN characteristics in 13 ears (from 10 infants) in our series depending on the laterality of deafness and presence of CND. CONCLUSIONS: This study demonstrates that there were diverse etiologies related to AN characteristics from infants with unilateral or bilateral profound HL. Association between CND and AN characteristics is suggestive but not solid at this moment and AN characteristics is not a fully penetrant feature of CND. PMID- 27260583 TI - Diphtheria: It is still prevalent!!! AB - BACKGROUND: Diphtheria is a respiratory infectious disease of childhood. It is a fatal disease and may cause complications if not recognized early and treated properly. Despite availability of effective vaccination it continues to be reported from many parts of the world particularly developing countries. OBJECTIVE: To assess the demographic and clinical characteristics of diphtheria patients, and the predictors of outcomes of respiratory diphtheria. METHODS: A prospective analysis of 180 patients with a clinical diagnosis of respiratory diphtheria admitted from 2011 to 2014 at a tertiary referral hospital. They were evaluated with respect to demographic details, immunization status, clinical features, complications and outcomes. RESULTS: Most common age group affected was children less than 5 years of age (87 cases, 48.33%). The peak incidence of diphtheria was seen in the months of September and October (111 cases, 62%). Majority of the patients were unimmunized (54%), followed by partially immunized (21%). The most common complication was respiratory in 80 cases (44%), followed by cardiac complications in 54 cases (30%), and renal (16%) and neurological complications (10%). Cardiac complications were associated with the highest mortality rate (63%). The presence of bull neck and pseudomembrane score >2 was associated with a high mortality. CONCLUSION: Diphtheria is still a preventable public health problem in many developing countries. Improved vaccination coverage, including booster dosage, coupled with early detection and effective treatment, may all reduce incidence and mortality. PMID- 27260584 TI - Surgical correction of bifid nose. AB - OBJECTIVES: Evaluation of the aesthetic outcome and functional aspect after surgical correction of bifid nose by combined Millard forked flap with external rhinoplasty BACKGROUND: Bifid nose is a rare congenital anomaly that results during facial development but the explicit mechanism is not clearly understood. Clinical findings are quite variable with a wide range of severity. Surgical correction still represents great challenge to facial plastic surgeons; extensive deformities in many cases, rarity of condition and paucity of publications are contributing factors. METHODS: Surgical correction of six patients with bifid nose by a combined Millard forked flap with external rhinoplasty RESULTS: The aesthetic and functional outcomes were acceptable for all patients and parents. There were no considerable postoperative complications. CONCLUSIONS: This approach is highly effective for various grades of bifid nose. Early management is preferable to avoid psychological morbidity. Secondary rhinoplasty is usually needed for cosmetic refinement. PMID- 27260585 TI - Case series of congenital heterotopic neuroglial tissue in the parapharyngeal space. AB - Cases of congenital heterotopic tissue presenting in the head and neck are frequent in the pediatric otolaryngology literature. Heterotopic glioneuronal tissue is rare and fewer than 20 cases of heterotopic glioneuronal tissue in the parapharyngeal space have been reported. We present two cases of infant children who were seen at the Children's Hospital of Pittsburgh in 2013 with glioneuronal heterotopic masses in the parapharyngeal space. PMID- 27260586 TI - Management of severe congenital laryngeal webs - a 12 year review. AB - OBJECTIVE: The aim of this study was to investigate respiratory and voice outcomes after open surgery for severe congenital laryngeal web. METHODS: Included were all patients treated for severe congenital glottic web (Cohen type 3 and 4) between 2002 and 2014. Demographic data, symptoms, endoscopic findings, type of operation, outcome and complications were analyzed. Open surgery was performed with division of the web and enlargement of the subglottis by a laryngotracheal reconstruction or an extended partial cricotracheal resection. RESULTS: Fourteen patients were included. Information on the pre-operative voice was available in 11 patients. Aphonia was present in 6 patients (55%), dysphonia was severe in 1 (9%), moderate in 2 (18%) and mild in 2 (18%). Median age at operation was 19.3 months. As a first line treatment, laryngotracheal reconstruction was performed in 12 patients, and an extended partial cricotracheal resection in 2. Median follow-up was 9.5 months. All patients were successfully decannulated in a median time of 4 months after first surgery. Voice was improved in 10/11 (91%). Post-operatively, 3 patients (27%) had good voice. Dysphonia was severe in 2 (18%), moderate in 3 (27%) and mild in 3 patients (27%). CONCLUSION: Open surgery for Cohen type 3 and 4 glottic web allowed establishing a patent airway with successful decannulation in all cases. Quality of voice was improved in 91%, however, voice results were variable. In our opinion a delicate operative technique described in the paper is important for optimal voice results. PMID- 27260587 TI - Peri-implant bony overgrowth as a cause of revision surgery in auditory osseointegrated implantation. AB - Implantation of auditory osseointegrated implants, also known as bone-anchored hearing systems (BAHS), represents a surgical option for select pediatric patients aged 5 years or older with hearing loss. Functional indications in this patient population include conductive or mixed hearing loss. Common complications of implantation include skin infections, chronic skin irritation, hypertrophic skin overgrowth, and loose abutments. In a case series of 15 pediatric patients, we discovered an unexpectedly high skin-related complication rate requiring surgical revision of 53%. During revision surgery, we discovered 5 patients who exhibited significant bony overgrowth at the abutment site, a complication infrequently noted in past literature. PMID- 27260588 TI - Castleman's disease: An unusually young presentation resulting in delayed diagnosis of a neck mass. AB - We present a case report of a two year old child with an enlarging neck mass over a two year period. Her work-up included blood investigations, radiological imaging and fine needle aspirations which were non-diagnostic. At age 4 she had excision of her neck mass and histopathologic examination revealed unicentric Castleman's disease. This is one of the youngest reported cases in the literature and highlights the need to include CD in the differential diagnosis of neck masses in young children. Castleman's disease (CD) is a rare disease of benign lymph node enlargement which most commonly occurs in adults. While the multi centric variant is associated with HIV and HHV-8 infection, the aetiology of unicentric disease remains uncertain. PMID- 27260590 TI - Corrigendum to "Does passive smoking induce sensorineural hearing loss in children?" [Int. J. Pediatr. Otorhinolaryngol. 78 (1) (2014) 46-49]. PMID- 27260589 TI - Which outcome measures are reported by clinical trials investigating OME treatment? A case for standardised reporting. AB - INTRODUCTION: Many different OME treatment trials have been published using different outcomes measures to evaluate the success of particular interventions. We set out to identify the variation in reporting of outcome measures in OME trials that exists at present. This has been achieved by reviewing published trials to determine which outcome measures have been reported. METHOD: The literature review was carried out using PUBMED database (1980 to 2013). Data were collected on the treatment outcomes reported, with particular focus on the methods of assessment and the number of treatment outcomes used in each study. RESULTS: The 171 studies identified used 12 broad treatment outcome measures. The most common outcome measure was OME resolution (48%) followed by hearing level (36%). Only 95 studies used a single outcome measure, with 76 studies using between 2 and 4 outcome measures. The method of assessment varied between studies that used the same treatment outcome measures. CONCLUSION: OME treatment trials report a wide range of measures and comparison across studies is thus difficult. Establishing a core set of outcome measures to be reported by all trials in the future could be useful, and would allow comprehensive comparison of different studies and minimise potential for reporting bias. PMID- 27260591 TI - Quality of life in children with Robin Sequence. AB - INTRODUCTION: Parents may play an important role during the management of children with Robin Sequence (RS). However, so far only one study has been done on both parent-reported health-related quality of life (HRQoL) and obstructive sleep apnea (OSA) symptoms in children with RS. METHODS: Overall, 63 children with RS, aged 1 and 18, were included in this cross-sectional study. Fifty-three parents of children with RS with a median age of 8.9 [IQR 5.1-12.7] completed questionnaires on HRQoL (OSA-18) and symptoms of OSA (the Brouillette score) in their child with RS. Ten children between 12 and 18 years filled out the self reported HRQoL questionnaire OSA-12. RESULTS: At cross-section, 10 children still had respiratory problems. Overall, parents of children with RS reported a lower HRQoL in their child compared with parents in the general population. Parents of children with RS who still had respiratory problems, i.e. OSA or airway support, reported significantly worse OSA-18 scores compared with parents of RS children without OSA. Children with RS themselves (n = 10) reported less physical suffering and less emotional distress on the OSA-12 compared with children in the norm population. Parental perceptions of OSA-related symptoms were accurate, except for the incidence of snoring. In assessing snoring, the multidimensional OSA-18 sleep domain was more informative. CONCLUSIONS: Parents of children with RS reported a lower HRQoL in their child compared with parents in the general population. Parental perceptions of health and HRQoL in children with RS might have an additional value to recognize and treat respiratory problems. PMID- 27260592 TI - Speech characteristics after articulation therapy in children with cleft palate and velopharyngeal dysfunction - A single case experimental design. AB - OBJECTIVE: The aim of this study was to investigate the impact of an intensive 10 week course of articulation therapy on articulation errors in cleft lip and palate patients who have Velopharyngeal Insufficiency (VPI), non-oral and passive cleft speech characteristics. METHODS: Five children with cleft palate (+/-cleft lip) with VPI and non-oral and passive cleft speech characteristics underwent 40 intensive articulation therapies over 10 weeks in a single case experimental design. The percentage of non-oral CSCs (NCSCs), passive CSCs (PCSCs), stimulable consonants (SC), correct consonants in word imitation (CCI), and correct consonants in picture naming (CCN) were captured at baseline, during intervention and in follow up phases. Visual analysis and two effect size indexes of Percentage of Nonoverlapping Data and Percentage of Improvement Rate Difference were analyzed. RESULTS: Articulation therapy resulted in visible decrease in NCSCs for all 5 participants across the intervention phases. Intervention was effective in changing percentage of passive CSCs in two different ways; it reduced the PCSCs in three cases and resulted in an increase in PCSCs in the other two cases. This was interpreted as intervention having changed the non-oral CSCs to consonants produced within the oral cavity but with passive characteristics affecting manner of production including weakness, nasalized plosives and nasal realizations of plosives and fricatives. Percent SC increased throughout the intervention period in all five patients. All participants demonstrated an increase in percentage of CCI and CCN suggesting an increase in the consonant inventory. Follow-up data showed that all the subjects were able to maintain their ability to articulate learned phonemes correctly even after a 4 week break from intervention. CONCLUSION: This single case experimental study supports the hypothesis that speech intervention in patients with VPI can result in an improvement in oral placements and passive CSCs. PMID- 27260593 TI - Parents' decisional conflict, self-determination and emotional experiences in pediatric otolaryngology: A prospective descriptive-comparative study. AB - OBJECTIVE: The aim of this study was to describe the level of decisional conflict experienced by parents considering surgery for their children and to determine if personal characteristics and emotional experiences vary as a function of whether or not parents experienced clinically significant levels of decisional conflict. METHODS: Sixty consecutive parents of children who underwent surgical consultation for elective otolaryngological procedures were prospectively enrolled. Participants completed the Decisional Conflict Scale, Basic Needs Satisfaction Scale, and the Positive and Negative Affect Schedule-Revised. RESULTS: Eight participants (13.3%) scored over 25 on the Decisional Conflict Scale, a previously defined cut-off indicating clinically significant decisional conflict. Parents who experienced significant decisional conflict felt less autonomous and less related or connected to others as compared to those who did not report significant decisional conflict. In addition, parents who experienced significant decisional conflict reported more negative emotions and fewer positive emotions during the surgical consultation visit. However, parents who reported significant decisional conflict did not report feeling less competent. CONCLUSIONS: Parental decision-making on whether their child should undergo elective pediatric otolaryngological surgery is a personal and emotional process. Parents' characteristics and experiences should be acknowledged and supported during the surgical consultation. Future research should aim to normalize the decision-making experience for parents, and to allow surgeons to be aware of the importance of decisional needs. PMID- 27260594 TI - Practice patterns in supraglottoplasty and perioperative care. AB - OBJECTIVES: Supraglottoplasty is the first-line surgical treatment for severe laryngomalacia. The purpose of this study is to determine the current trends of practice patterns in managing children who require supraglottoplasty. METHODS: A 25-question survey regarding supraglottoplasty techniques and perioperative management was sent by e-mail to 274 physician members of the Society for Ear, Nose and Throat Advances in Children (SENTAC). RESULTS: 101 surgeons responded and 72% of respondents were in academic practice (p < 0.0001). All four United States regions, Canada and the United Kingdom were represented. The most commonly reported age of patients undergoing supraglottoplasty was 1-3 months (62% of respondents). Indications include worsening airway symptoms (43%), failure to thrive (41%) and worsening feeding (10%). The majority of respondents (89%) treat these patients for reflux with 54% prescribing PPIs and 41% prescribing H2 blockers. Cold steel is the most popular surgical technique (73%) followed by laser (14%), microdebrider (10%) and coblator (3%) (p < 0.0001). Most respondents (92%) administer intraoperative steroids with the majority of them choosing dexamethasone (99%). Perioperative antibiotics are administered by 23% of respondents. Almost all respondents admit their patients for post-operative observation (99%) and 53% of these admit to PICU rather than step-down or floor status. The level of care is associated with the number of supraglottoplasties performed per year (p = 0.009) and with the geographic region (p = 0.02). Surgeons who perform fewer supraglottoplasties tend to admit to a higher level of care. Those in the South and Northeast regions tend to admit more to floor status. Only 13% routinely keep patients intubated post-operatively. CONCLUSIONS: This provider survey study highlights some significant variations and trends in practice patterns of otolaryngologists who perform supraglottoplasty. The majority utilizes anti-reflux pharmacotherapy; however, there is no consensus in which type. The method for supraglottoplasty also varies with cold steel being the most popular, although no single method has been shown to be superior. There is variation in post-operative care with trends for keeping patients extubated and admitting them to an intensive care. With the importance of safe, effective, and also cost-conscious care, further studies are needed to understand the optimal management of those who undergo supraglottoplasty. PMID- 27260595 TI - Efficacy of auditory-verbal therapy in children with hearing impairment: A systematic review from 1993 to 2015. AB - OBJECTIVES: Auditory verbal therapy (AVT) is one of the primary treatment approaches for developing spoken language in children with hearing impairment (HI), but its outcomes have not been thoroughly investigated. The current study aimed to systematically review past studies investigating AVT outcomes in children with HI. METHODS: A systematic search was conducted in six databases. Fourteen articles that met the final inclusion criteria were grouped under three categories based on the outcome measures: receptive and expressive language development, auditory/speech perception and mainstreaming. RESULTS: Articles under "receptive and expressive language development" category indicated AVT can even help children with HI beyond three years of age to develop age appropriate language skills and catch up with their hearing peers. Articles under "auditory /speech perception" category suggested that children receiving AVT can learn to recognize words accurately even in the presence of background noise. Articles grouped under "mainstreaming" category indicated that children receiving AVT can be successfully mainstreamed. CONCLUSION: Although studies suggest that AVT can have a positive impact on developing speech and language skills in children with HI, it is difficult to generalize these findings due to limited evidence. Future studies should utilize well-controlled group designs to minimize the role of external variables as well as strengthen the evidence-base for AVT. PMID- 27260596 TI - Maxillary dentoskeletal changes 1-year after adenotonsillectomy. AB - OBJECTIVE: To measure the maxillary dentoskeletal and soft tissue changes of severely obstructed mouth breathing (MB) young children who had their mode of breathing normalized after adenotonsillectomy (T&A), in comparison with a matched group of severely obstructed untreated MB children (CG). METHODS: Seventy patients who had an Ear, Nose, and Throat examination (ENT), including flexible nasal endoscopy, to confirm the severe obstruction of the upper airways and the indication of T&A composed the sample. Cephalograms and dental casts were available from the patient's orthodontic records. Treatment group (TG) and CG included 35 children each. Groups were matched by gender (24 males and 11 females in each group), age (TG, 6.7 +/- 1.8 years; CG, 6.9 +/- 2.3 years), tooth development (TG, 13 primary dentition, 22 mixed dentition; CG, 14 primary dentition, 21 mixed dentition), and skeletal maturation status. Records were taken at baseline (T0) and 1-year after T&A (T1) for TG; while CG records were taken with a 1-year interval. Dentoskeletal measurements were performed in the lateral cephalograms, and dental casts were used to assess the palatal volume and occlusal changes. RESULTS: TG showed a significant increase (503.3 mm(3), P < 0.001) in the palatal volume (10% of change), while CG palatal volume was stable. No dimensional occlusal changes were detected between T0 and T1 in both groups. Significant downward (point A, 2.1 mm; ANS, 2.1 mm) and forward displacements (point A, 0.7 mm; ANS, 1 mm) of the anterior region of the maxilla were observed in the TG, but CG presented only significant downward displacement (point A, 1.8 mm; ANS, 1.4 mm). The maxillary posterior region (PNS, PTM, and Molar) displaced downward in both groups (P < 0.05), however no sagittal change was found. The palatal plane inclination was stable in both groups. CONCLUSIONS: TG presented significant increase in the palatal volume and in the forward displacement of the maxilla. No other significant maxillary dentoskeletal changes were found. PMID- 27260597 TI - Deaf or hard of hearing children in Saudi Arabia: Status of early intervention services. AB - OBJECTIVE: This study aims to determine the status of early intervention services provided to children who are deaf or hard of hearing and their parents/caregivers from birth to five years of age at two main state hospitals in Riyadh, Saudi Arabia, based on their parents' perceptions. METHOD: A descriptive quantitative research design was used to determine the status of early intervention services for deaf or hard of hearing children in Saudi Arabia based on their parents' perceptions. Semistructured interviews based on a questionnaire were conducted with 60 research participants from two main state hospitals where early detection and intervention services are provided. A purposive sampling technique was employed. Descriptive and inferential statistical analyses were performed on the data collected. RESULTS: The participants' children were diagnosed at a substantially late age, resulting in delayed ages for initial hearing aid fitting and enrolment in early intervention services. A significant relationship was found between the residential area of the participants and timely access to intervention services. The results indicated that participants residing in Riyadh were fitted with hearing aids and enrolled into EI services earlier than those living outside of Riyadh. The delivery of information also emerged as a weakness in the EI system for the majority of participants. CONCLUSION: The findings of the study suggested that limited services of detection and intervention for deaf or hard of hearing children and residential area of participants are likely to be barriers to early access to intervention services. It is proposed that the benefits of UNHS accompanied by appropriate early intervention services should be made available in all regions throughout Saudi Arabia. PMID- 27260598 TI - Voice onset time of alveolar stop /t/ and realization of unaspirated affricates associated with Mandarin-speaking children with repaired cleft palate. AB - PURPOSE: To examine perceptually the realization of unaspirated affricates and voice onset time (VOT) features of /t/ in Mandarin-speaking children with repaired cleft palate, and to explore the difficulties associated with unaspirated affricate production from the perspective of the VOT of /t/. METHOD: Twenty-three children with repaired cleft palate and 22 age-matched typical native Mandarin speakers were recruited. Speakers with cleft palate were allocated into two groups based on expert perceptual judgment of nasality: one group with perceived normal resonance (PNR) (n = 14, average age = 9.3 years), and another group with perceived hypernasal resonance (PHR) (n = 9, average age = 10.3 years). INTERVENTION: Stimuli were collected through a series of picture naming tasks, targeting the production of initial consonants /t/ and three unaspirated Mandarin affricates /ts, ts, tc/. The productions of each affricate were evaluated by two experienced speech therapists. The VOT of /t/ was measured using PRAAT speech analysis software. RESULT: The majority of unaspirated affricates were omitted and/or weakly realized by the group of PHR speakers, but not for the PNR group. A significantly smaller mean VOT value associated with /t/ was identified for the PHR group, as compared to the PNR group. A group difference for VOT value was not found between the PNR group and the typical control group. CONCLUSION: The voicing features of /t/ and omitted/weak realization of unaspirated affricates identified in the PHR group indicated that the deviant production of unaspirated affricates in the cleft palate group could be associated with the voicing characteristics of the alveolar stop /t/, and this merits further investigation. PMID- 27260599 TI - Wideband reflectance measurements in newborns: Relationship to otoscopic findings. AB - OBJECTIVES: Newborn hearing screening includes testing with otoacoustic emissions and the auditory brainstem response. Unfortunately, both tests are affected by the presence of material in the ear canal and middle ear such as vernix, meconium, and amniotic fluid. The objective of this study was to determine to what extent occlusion of the ear canal as seen on otoscopy affects wideband energy reflectance measurements in newborns. A secondary objective was to obtain additional normative wideband reflectance data in newborns. METHODS: Newborns from a well-baby nursery were enrolled. Wideband energy reflectance measurements and otoscopy were done immediately after the hearing screening. Occlusion of the ear canal as seen on otoscopy was described on a scale of 0-100%. RESULTS: A total of 156 babies were enrolled (mean age = 25 hours). A statistically significant difference in the reflectance at ambient pressure was found between the 0-70% and 80-100% occlusion groups. There was no significant difference in reflectance between the right and the left ears. The median reflectance pattern generally followed that of previous studies but in certain frequency regions the present reflectance values were higher. CONCLUSION: A significant increase in reflectance occurs when 70%-80% of the ear-canal diameter is occluded. Taking otoscopy findings into account may improve the interpretation of reflectance measurements. However, further studies are required to better establish the relationship between canal occlusion and reflectance. PMID- 27260600 TI - The effect of device use after sequential bilateral cochlear implantation in children: An electrophysiological approach. AB - OBJECTIVES: In many studies evaluating the effect of sequential bilateral cochlear implantation in congenitally deaf children, device use is not taken into account. In this study, however, device use was analyzed in relation to auditory brainstem maturation and speech recognition, which were measured in children with early-onset deafness, 5-6 years after bilateral cochlear implantation. We hypothesized that auditory brainstem maturation is mostly functionally driven by auditory stimulation and is therefore influenced by device use and not mainly by inter-implant delay. METHODS: Twenty-one children participated and had inter implant delays between 1.2 and 7.2 years. The electrically-evoked auditory brainstem response was measured for both implants separately. The difference in interaural wave V latency and speech recognition between both implants were used in the analyses. Device use was measured with a Likert scale. RESULTS: Results showed that the less the second device is used, the larger the difference in interaural wave V latencies is, which consequently leads to larger differences in interaural speech recognition. CONCLUSIONS: In children with early-onset deafness, after various periods of unilateral deprivation, full-time device use can lead to similar auditory brainstem responses and speech recognition between both ears. Therefore, device use should be considered as a relevant factor contributing to outcomes after sequential bilateral cochlear implantation. These results are indicative for a longer window between implantations in children with early-onset deafness to obtain symmetrical auditory pathway maturation than is mentioned in the literature. Results, however, must be interpreted as preliminary findings as actual device use with data logging was not yet available at the time of the study. PMID- 27260601 TI - Association of serum eosinophilia and total immunoglobulin E concentration with the risk of allergic symptoms and allergic sensitization, respectively: A 2-year follow-up study. AB - OBJECTIVES: Serum eosinophil percentage (SEP), eosinophil cationic protein (ECP) concentration, and total IgE (TIgE) concentration are known to increase in patients with allergic disease; however, the relevance of these elevated markers in children with negative allergic test results remains unclear. Therefore, this 2-year follow-up study aimed to investigate whether SEP, ECP concentration, and TIgE concentration are associated with an increased risk for allergic sensitization and allergic symptoms. METHODS: In 2012, SEP, ECP concentration, and TIgE concentration of third- and fourth-grade students from 6 elementary schools were measured. Skin prick test was performed, and the presence of allergic nasal symptoms was investigated using a questionnaire. In 2014, the same examinations were performed in the same set of students, who were then in the fifth and sixth grades, respectively, of the same schools. The cut-off value and usefulness of serologic markers (eosinophil count, ECP concentration, and TIgE concentration) were calculated using the receiver operating characteristic curve. RESULTS: Serum eosinophil percentage (cut-off value, 3.8%) was associated with the newly developed allergic nasal symptoms (sensitivity, 77.9; specificity, 41.8). A high serum TIgE concentration (cut-off value, 17.7 IU/mL) was also associated with the risk for allergic sensitization (sensitivity, 46.3; specificity, 85.3). CONCLUSION: SEP and TIgE concentration were associated with the development of allergic symptoms and allergic sensitization, respectively, 2 years after the first examination. PMID- 27260602 TI - Evaluation of olfactory function in children with allergic rhinitis and nonallergic rhinitis. AB - OBJECTIVES: Allergic rhinitis (AR) occurs when the symptoms of rhinitis arise as a result of allergen-induced nasal mucosal inflammation. In the presence of rhinitis symptoms without infection or an allergic reaction in the nose, non allergic rhinitis (NAR) is considered. Adults with these diseases have increased frequency of olfactory dysfunction. The aim of the present study is to assess olfactory function in children with AR and NAR. METHODS: A total of 77 children (aged six to 18 years) with AR and NAR were included in the study. The control group consisted of 45 healthy children. Sniffin' Sticks test was applied to both groups. The association between odor scores and demographic, clinical, and laboratory results was investigated. RESULTS: Forty two patients had allergic rhinitis. No significant difference was observed between patients with rhinitis and healthy controls with respect to odor scores. No association was observed between odor scores and the severity of rhinitis and the laboratory results of the patient groups. Odor identification and total odor scores of the patients with rhinitis lasting for longer than three years were significantly lower than those in the patient group with rhinitis lasting for one to three years. In the AR and control groups, the odor scores were found to increase with age. CONCLUSIONS: When compared with healthy children, children with allergic rhinitis and non-allergic rhinitis were not found to have reduced olfactory function. The duration of rhinitis may be associated with the olfactory dysfunction in children with rhinitis. PMID- 27260603 TI - Post-intubation acute laryngeal injuries in infants and children: A new classification system. AB - OBJECTIVE: To compare the Classification of Acute Laryngeal Injuries (CALI) with other classifications to determine which of these offers the greatest sensitivity and specificity in predicting the development of subglottic stenosis. METHODS: All children intubated for the first time in the pediatric intensive care unit were included and subjected to flexible fiber-optic laryngoscopy (FFL) within 8 h of extubation. Their injuries were categorized using the CALI, as well as adapted classifications from Lindholm, Colice and Benjamin. The children were followed up to determine who developed subglottic stenosis. RESULTS: This study included 194 children, with a median age of 2.67 months. The sensitivity and specificity of the CALI were 90% and 73%, respectively. The CALI showed greater specificity than the adapted classifications from Colice and Benjamin (p < 0.001 for both), and greater sensitivity than the adapted classification from Lindholm (p < 0.001). CONCLUSIONS: Based on the CALI, 90% of children who developed subglottic stenosis had moderate to severe injuries on the initial FFL. The CALI includes all injury types described by Benjamin, as well as a proposed severity scale for these lesions, and was predictive of the development of chronic laryngeal injury. PMID- 27260604 TI - Topical versus oral antibiotics, with or without corticosteroids, in the treatment of tympanostomy tube otorrhea. AB - OBJECTIVE: Antibiotic treatment is the standard of care for tympanostomy tube otorrhea. This meta-analysis aims to evaluate the efficacy of topical antibiotics with or without corticosteroids versus oral antibiotics in the treatment of tube otorrhea in children. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and ProQuest. REVIEW METHODS: The above databases were searched using a search strategy for randomized controlled trials for optimal treatment of tube otorrhea in the pediatric population. PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines were followed. Primary outcome was cure (i.e. clearance of otorrhea) at 2-3 weeks. Secondary outcomes were microbiological eradication and complications such as dermatitis and diarrhea. The incidence of these events was defined as dichotomous variables and expressed as a risk ratio (RR) and number needed to benefit (NNTB) in a random-effects model. RESULTS: We identified 1491 articles and selected 4 randomized controlled trials which met our inclusion criteria. Topical treatment had better cure (NNTB = 4.7, pooled RR = 1.35, p < 0.001) and microbiological eradication (NNTB = 3.5, pooled RR = 1.47, p < 0.001 among 3 of the studies) than oral antibiotics. Oral antibiotics had higher risk of diarrhea (pooled RR = 21.5, 95% CI 8.00-58.0, p < 0.001, Number needed to harm (NNTH) = 5.4) and dermatitis (pooled RR = 3.14, 95% CI 1.20-8.20, p = 0.019, NNTH = 32). The use of topical steroids in addition to topical antibiotics was associated with a higher cure rate (pooled RR = 1.59, p < 0.001 vs pooled RR = 1.57, p = 0.293). CONCLUSION: Topical antibiotics should be the recommended treatment for management of tympanostomy tube otorrhea in view of its significantly improved clinical and microbiological efficacy with lower risk of systemic toxicity as compared to oral antibiotics. Further research is necessary to confirm the benefits of topical corticosteroids as an adjunct to topical antibiotics. PMID- 27260605 TI - MALDI-TOF mass spectrometry reveals a highly complex bacterial profile of otitis media with effusion. AB - OBJECTIVES: With conventional microbiological methods, a significant proportion of middle ear effusion (MEE) proves to be sterile. Accurate molecular biological techniques have been used to identify only pathogenic bacteria. Matrix assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an adequate tool for the precise and simultaneous identification of a wide range of bacterial species from a small sample. The aim of this study was to explore the use of MALDI-TOF MS in revealing the frequency and complexity of bacterial flora in MEE in otitis media with effusion (OME). METHODS: MEEs from 40 children with chronic otitis media with effusion were examined for 2000 pathogenic, facultative pathogenic and nonpathogenic bacterial species using MALDI-TOF MS. Two middle ear samples from children who underwent cochlear implantation with healthy middle ear were also examined in the same way. RESULTS: No bacteria were found in healthy control samples and 92% of OME samples were positive for at least one bacterium. In 52% of the samples more than one bacterium was identified. In total 39 bacterial species were found in the middle ear samples. Of the positive samples 19% contained those pathogens which were previously thought to contribute OME. CONCLUSION: MALDI-TOF MS is a suitable tool for identifying a wide range of bacterial species in MEE. Results show that bacterial flora of MEE in OME is more diverse and abundant than it was formerly thought. This previously unreported bacterial invasion may help to obtain proper understanding and therapy of OME. PMID- 27260606 TI - Effect of adenotonsillectomy on attention deficit-hyperactivity disorder in children with adenotonsillar hypertrophy: A prospective cohort study. AB - BACKGROUND: This study was conducted to explore the effect of adenotonsillectomy on the improvement of attention deficit hyperactivity disorder (ADHD) symptoms in children with adenotonsillar hypertrophy. METHODS: This prospective cohort study was conducted on 59 children aged 6-12 years with adenotonsillar hypertrophy and ADHD who were candidates for adenotonsillectomy at Besat Hospital, Hamadan University of Medical Sciences, in 2014. The status of ADHD was evaluated at baseline and one and three months after surgery using Conners' Rating Scales. RESULTS: Of 59 children with ADHD (35 boys and 24 girls), 41 improved one month after surgery and 51 after three months. Only 8 children had no improvement. The Conners' score decreased significantly from 71.37 at baseline to 61.31 (P = 0.001) and 49.14 (P = 0.001) one and three months after surgery, respectively. The score of attention deficit and hyperactivity decreased from 1.76 and 2.10 at baseline to 1.52 and 1.83 after one month (P = 0.001) and to 1.24 and 1.52 after three months (P = 0.001), respectively. The results were statistically significant for both boys and girls. CONCLUSION: This study indicated that adenotonsillectomy can significantly improve ADHD in children with adenotonsillar hypertrophy and help them return to normal life. PMID- 27260607 TI - Odontogenic lesions in a pediatric population: Review of the literature and presentation of 745 cases. AB - OBJECTIVES: Pediatric odontogenic lesions are rare clinical entities and are not well addressed in the otolaryngology literature. Knowledge of the biologic and clinical behavior of these lesions and their basic features such as location and age are key aspects for otolaryngologists in developing an early clinical differential diagnosis, such that they can provide adequate treatment. METHODS: Six thousand histologically-diagnosed odontogenic lesions from a 40-year period were reviewed. Pediatric patients (745 cases, 12.7%) aged up to 17 years were selected and reevaluated. The patients were divided into three age groups according to dentition periods: primary dentition (0-5 years), mixed dentition (6 12 years), and permanent dentition (13-17 years). Clinical data, including age, sex, and location, were collected from pathology records. RESULTS: Of the total of 745 cases, 596 specimens (80%) were diagnosed as odontogenic cysts and 149 specimens (20%) were diagnosed as odontogenic tumors. The most frequent odontogenic cysts were radicular cysts (48.4%), followed by dentigerous cysts (16.7%). The most common odontogenic tumor was odontoma (8.05%). CONCLUSION: This study shows that all odontogenic lesions in the pediatric group are benign. Odontogenic tumors are relatively rare in this age group. Knowledge of the biological and histopathological behaviors of odontogenic lesions and their basic features such as location and age is a key aspect for developing an early clinical differential diagnosis and providing adequate treatment. PMID- 27260608 TI - Systematic review and case report: Intracranial complications of pediatric sinusitis. AB - CONTEXT: Intracranial complications of rhinosinusitis are rare in the post antibiotic era. However, due to potentially devastating outcomes, prompt recognition and management are essential. OBJECTIVE: This study aims to perform the first systematic review of the intracranial complications of rhinosinusitis in order to better characterize their clinical presentation, diagnosis, and treatment, and report a case of frontal lobe empyema secondary to pediatric frontoethmoid sinusitis. DATA SOURCES: Ovid MEDLINE, Cochrane Library, and Google Scholar. STUDY SELECTION: Full-text, peer-reviewed journal publications from 1947 to January 1, 2015 in English; focus on intracranial complications of sinusitis; pediatric patients (<18 years of age); studies including data on diagnostic workup and treatment. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Sixteen studies involving 180 patients were included. An overwhelming majority of patients were young adolescent males (70%). The most common intracranial complications were subdural empyema (49%), epidural abscess (36%), cerebral abscess (21%), and meningitis (10%). Patients most often presented with nonspecific symptoms such as headache, fever, nausea and vomiting. Computed tomography with contrast or magnetic resonance imaging confirmed the diagnosis when intracranial complications were suspected. Typical treatment included surgical incision and drainage, often involving joint neurosurgical and otolaryngological procedures, combined with a long course of antibiotics. The morbidity rate was 27%, and the mortality rate was 3.3%. LIMITATIONS: All studies were retrospective chart reviews, case series or case reports. CONCLUSIONS: A review of the currently available literature shows that with a high degree of suspicion, multidisciplinary cooperation and aggressive treatment, favorable outcomes are attainable. The most effective surgical treatment for intracranial complications remains unclear and should be investigated further. PMID- 27260609 TI - Histological analysis of retraction pocket pars tensa of tympanic membrane in children. AB - AIMS: Histological and histochemical analysis of retraction pocket of pars tensa of tympanic membrane in children. Identification of morphological abnormalities in comparison with a healthy tympanic membrane as it is described in standard textbook. Identification of signs typical for cholesteatoma and support for a retraction theory of cholesteatoma formation. STUDY DESIGN: A prospective study analysing 31 samples of retraction pockets taken during surgery. DEPARTMENTS: University Hospital, Children's Medical Centre METHODS: Samples of retraction pockets were processed by a standard process for light microscopy, stained by haematoxylin-eosin. Van Gieson's stain was used for differential staining of collagen, Verhoeff's stain for elastic fibre tissues, Alcian blue for acidic polysaccharides and PAS (Periodic Acid Schiff) method for basement membrane polysaccharides. RESULTS: The following findings were observed in the samples of retraction pockets: hyperkeratosis (100%), hypervascularisations (100%), subepithelial fragmented elastic fibres (96%), myxoid changes (87%), subepithelial inflammatory infiltration (84%), rete pegs (71%), papilomatosis (71%), intraepithelial inflammatory cellularizations, (48%), intraepithelial spongiosis (16%) and parakeratosis (3%). No basement membrane continuity interruptions were observed. Thickness of retraction pocket, thickness of epidermis, occurrence of rete pegs and frequency of fragmented elastic fibres was higher in a Grade III stage RP than Grade II stage RP (according to Charachon). CONCLUSION: Morphological abnormalities in the structure of retraction pockets in comparison with a healthy tympanic membrane were described. The changes are typical for a structure of cholesteatoma (these changes are common in matrix and perimatrix), supporting retraction theory of its origin. Our observations show that it is inflammation that probably plays a key role in the pathogenesis of retraction pocket. The frequency of some of the changes increases with the stage of retraction pocket (II-III according to Charachon). Basement membrane continuity interruptions are not typical for retraction pockets. PMID- 27260610 TI - Post-transplant lymphoproliferative disorder of the pediatric airway: Presentation and management. AB - OBJECTIVE: Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression with little consensus on its evaluation and management. The purpose of this contemporary review is to describe a pediatric patient with PTLD of the airway and review the literature to provide multidisciplinary recommendations regarding management. DATA SOURCES: Retrospective chart and literature review. REVIEW METHODS: A pediatric patient with PTLD of the airway is described. An extensive literature search to review the existing data on pediatric PTLD of the upper airway was also performed. RESULTS: A pediatric patient with mixed fetal/embryonal hepatoblastoma developed laryngo-tracheal PTLD following liver transplantation. Diagnostic positron emission tomography (PET) scan demonstrated multiple sites of abnormal fluorodeoxyglucose (FDG) uptake within the larynx, distal esophagus, cervical lymph nodes, and abdomen concerning for PTLD. Laryngeal biopsy demonstrated Epstein-Barr virus (EBV) positive cells confirming the diagnosis. Rituximab therapy and reduction of immunosuppression resulted in resolution of his laryngeal disease in 3 months. An extensive literature search to review the existing data on pediatric PTLD of the larynx and trachea revealed 14 reported cases. CONCLUSIONS: PTLD of the pediatric airway is an EBV-associated disease that requires a high index of suspicion as patients can often present with non specific signs and symptoms but progress to have significant airway compromise. Evaluation consists of peripheral blood polymerase chain reaction (PCR) assays, biopsy, and PET/CT imaging. Management options include reduction of immunosuppression and/or systemic therapies. PMID- 27260611 TI - General health, otitis media, nasopharyngeal carriage and middle ear microbiology in Northern Territory Aboriginal children vaccinated during consecutive periods of 10-valent or 13-valent pneumococcal conjugate vaccines. AB - OBJECTIVES: This study aims to monitor the prevalence of suppurative otitis media in remote Indigenous communities after introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2011. We previously reported a decline in suppurative OM following replacement of PCV7 by 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) in October 2009. METHODS: We continued regular surveillance in remote Indigenous communities between February 2010 and August 2013. This analysis reports the general health, otitis media (OM), nasopharyngeal (NP) carriage and middle ear microbiology in children less than 36 months of age who received a primary course of at least two doses of PHiD-CV10 or PCV13, and not more than one dose of another pneumococcal vaccine. RESULTS: Mean ages of 511 PHiD-CV10- and 140 PCV13-vaccinated children were 19 and 13 months, respectively. Most children received 3-dose non-mixed PCV schedules. At the time of assessment, general health was poor and prevalence of risk factors was high in both groups: overall, around 14% of children had scabies, 20% had impetigo, 59% had runny nose and 39% had cough. Average household size was 8 persons, and 60% of the mothers smoked. Bilaterally normal middle ears were detected in 10% and 7%, respectively. OM with effusion (OME), almost all bilateral, was diagnosed in 52% and 50%, any suppurative OM (acute OM or any tympanic membrane perforation [TMP]) in 37% and 41%, and TMP in 14% and 12%, respectively. Children in the PCV13 group had significantly less NP carriage of combined Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) (62% versus 51%) but significantly more polymicrobial (Spn and NTHi) middle ear cultures (12% versus 43%), and significantly less Staphylococcus aureus-positive middle ears (40% versus 7%). Although NP carriage of pneumococcal serotype 19A was low in the PCV13 group, serotypes 19F and 23F persist. CONCLUSIONS: The general health, particularly ear health, of little children in remote Australian Indigenous communities remains in crisis. In particular, transition to PCV13 did not show substantial further improvement in ear health. Possible vaccine-related differences in microbiology, including potential beneficial effects of PHiD-CV10 on NTHi infection, need to be further evaluated in randomised trials. PMID- 27260612 TI - Tips for children's better cooperation during the examination of the head and neck: A Delphi method. AB - OBJECTIVE: To obtain and rate tips for the head and neck examination in children. METHODS: A two-round Delphi method study was conducted to survey 13 practising paediatric otolaryngologists (PO) in North America and Europe to obtain tips on how to approach a 2- to 6-year-old child for head and neck examination. The tips were rated by the PO according to their frequency of utilization and usefulness on a scale of 1 (high) to 6 (low). One-sample Wilcoxon signed rank tests were used to evaluate each tip according to frequency of use and success rate. "Top Tips" were identified when both their Wilcoxon p-values were still significant, after a Bonferroni correction. An exact chi-square test for equality of proportions was used to determine the age groups for which satisfactory tips are to be favoured. RESULTS: The panellists rated forty-three tips. Seven tips obtained a p-value <=0.001 for the frequency of use and usefulness in all age groups with an emphasis on the initial moments: eye contact, mood assessment, approach behaviour and strategy. Six more tips proved to be satisfactory for specific age groups without reaching the top tip significance level. CONCLUSIONS: Seven tips to approach a 2- to 6-year-old child reached a top consensus between the experts. Initial eye contact with the child and mood assessment are essential for a satisfactory outcome. The use of a gentle approach with explanation of each step of the physical exam and avoidance of pain are also important. PMID- 27260613 TI - Vibrant SoundBridge combined with auricle reconstruction for bilateral congenital aural atresia. AB - OBJECTIVES: To report an integrating surgical method of Vibrant SoundBridge (VSB) implant and auricle reconstruction. METHODS: 4 cases of congenital bilateral external/middle ear malformation were enrolled. All of them were diagnosed as bilateral bony atresia and grade III microtia. Stapes vibroplasty was performed for all subjects in one operation with auricle reconstruction stage 3. The clinical information and hearing outcomes were analyzed. RESULTS: Satisfied aesthetic outcomes were confirmed by sculptured outline and symmetric shape on both sides. Mean improvement in hearing threshold with VSB activation was 25.9 dB HL, while mean scores of speech recognition test were 21.8-46.3%. CONCLUSION: Combined surgical method of VSB implant and aesthetic reconstruction is safe and efficient for congenital external/middle ear malformation case. PMID- 27260614 TI - Family presence during cardiopulmonary resuscitation: Evidence-based guidelines? PMID- 27260615 TI - Performance-Based Agreements in Italy: 'Trendy Outcomes' or Mere Illusions? PMID- 27260616 TI - Do self-reported concussions have cumulative or enduring effects on drivers' anticipation of traffic hazards? AB - AIM: To investigate the cumulative effect of multiple self-reported concussions and the enduring effect of concussion on drivers' hazard perception ability. It was hypothesized: (1) that individuals reporting multiple previous concussions would be slower to anticipate traffic hazards than individuals reporting either one previous concussion or none; and (2) that individuals reporting a concussion within the past 3 months would be slower to anticipate traffic hazards than individuals reporting either an earlier concussion or no prior concussion. METHOD: Two hundred and eighty-two predominantly young drivers (nconcussed = 68, Mage = 21.57 years, SDage = 6.99 years, 66% female) completed a validated hazard perception test (HPT) and measures of emotional, cognitive, health and driving status. RESULTS: A one-way analysis of variance showed that there was no significant effect of concussion number on HPT response times. Similarly, pairwise comparisons showed no significant differences between the HPT response times of individuals reporting a concussion within the previous 3 months, individuals reporting an earlier concussion and the never concussed group. CONCLUSION: The findings suggest that previous concussions do not adversely affect young drivers' ability to anticipate traffic hazards; however, due to reliance on self-reports of concussion history, further prospective longitudinal research is needed. PMID- 27260617 TI - A novel hypoxia-induced miR-147a regulates cell proliferation through a positive feedback loop of stabilizing HIF-1alpha. AB - Hypoxia is a general event in solid tumor growth. Therefore, induced cellular responses by hypoxia are important for tumorigenesis and tumor growth. MicroRNAs (miRNAs) have recently emerged as important regulators of hypoxia induced cellular responses. Here we report that miR-147a is a novel and crucial hypoxia induced miRNA. HIF-1alpha up-regulates the expression of miR-147a, and miR-147a in turn stabilizes and accumulates HIF-1alpha protein via directly targeting HIF 3alpha, a dominant negative regulator of HIF-1alpha. Subsequent studies in xenograft mouse model reveal that miR-147a is capable of inhibiting tumor growth. Collectively, these data demonstrate a positive feedback loop between HIF-1alpha, miR-147a and HIF-3alpha, which provide a new insight into the mechanism of miR 147a induced cell proliferation arrest under hypoxia. PMID- 27260618 TI - Heterologous expression of Streptococcus mutans Cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence. AB - In S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors. PMID- 27260619 TI - Microbial pathogens in source and treated waters from drinking water treatment plants in the United States and implications for human health. AB - An occurrence survey was conducted on selected pathogens in source and treated drinking water collected from 25 drinking water treatment plants (DWTPs) in the United States. Water samples were analyzed for the protozoa Giardia and Cryptosporidium (EPA Method 1623); the fungi Aspergillus fumigatus, Aspergillus niger and Aspergillus terreus (quantitative PCR [qPCR]); and the bacteria Legionella pneumophila (qPCR), Mycobacterium avium, M. avium subspecies paratuberculosis, and Mycobacterium intracellulare (qPCR and culture). Cryptosporidium and Giardia were detected in 25% and in 46% of the source water samples, respectively (treated waters were not tested). Aspergillus fumigatus was the most commonly detected fungus in source waters (48%) but none of the three fungi were detected in treated water. Legionella pneumophila was detected in 25% of the source water samples but in only 4% of treated water samples. M. avium and M. intracellulare were both detected in 25% of source water, while all three mycobacteria were detected in 36% of treated water samples. Five species of mycobacteria, Mycobacterium mucogenicum, Mycobacterium phocaicum, Mycobacterium triplex, Mycobacterium fortuitum, and Mycobacterium lentiflavum were cultured from treated water samples. Although these DWTPs represent a fraction of those in the U.S., the results suggest that many of these pathogens are widespread in source waters but that treatment is generally effective in reducing them to below detection limits. The one exception is the mycobacteria, which were commonly detected in treated water, even when not detected in source waters. PMID- 27260621 TI - Response to. PMID- 27260620 TI - Letter to the Editor Re: Andrew Turner, Emily R. Kearl, Kevin R. Solman Lead and other toxic metals in playground paints from South West England Science of the Total Environment 544 (2016) 460-466. AB - Turner's paper emphasizes "oral bioaccessibility" instead of focusing solely on total lead content. There is no evidence that solubility testing for lead levels in paint correlates with absorption or blood lead levels in exposed children. There are many considerations in determining exposure hazards to paint that are not evaluated in assessing solubility. Although we strongly support the conclusions and recommendations of the study, we are concerned that by reporting "oral bioaccessibility" others will focus on solubility in developing regulatory standards for lead levels in paint or in conducting exposure assessments. Standards for lead in paint should continue to be based on total lead content, not "oral bioaccessibility." PMID- 27260622 TI - [Confocal microscopy as an early relapse marker after keratoplasty due to Fusarium solani keratitis]. AB - In the case of therapy-resistant keratitis an infection with Fusarium solani should be taken into consideration as a rare but very severe eye disease. In the majority of cases Fusarium solani keratitis will result in a protracted clinical course despite aggressive medicinal and surgical interventions. We describe the case of a referred patient after intensive topical, intracameral and systemic antibacterial and antimycotic therapy as well as surgical treatment with emergency keratoplasty a chaud because of Fusarium solani keratitis. The patient presented to our department with persistent discomfort for further therapeutic interventions. Using confocal microscopy we were able to demonstrate the presence of fungal hyphae in the host cornea and the graft, which was important for making further surgical decisions. Furthermore, this emphasizes the role of confocal microscopy as an early relapse marker during the clinical monitoring. PMID- 27260623 TI - [Vitreous metastasis of malignant cutaneous melanoma during treatment with ipilimumab]. AB - An isolated metastasis of the vitreous body from a malignant cutaneous melanoma without involvement of the choroid is an extremely rare occurrence. We report on the case of a 59-year-old female patient who presented with a vitreous body metastasis during systemic treatment with the anti-cytotoxic T lymphocyte associated antigen (anti-CTLA 4) antibody ipilimumab. This case report underlines the diagnostic difficulties in such cases and points out the risk of metastasis in immune-privileged sites under systemic immunotherapy. PMID- 27260624 TI - [Corneal donation : Dilemma between growing demand and declining donor rate]. AB - BACKGROUND: One of the most important requirements for successful corneal transplantation is the availability of donor tissue and thus the approval for postmortem corneal tissue donation. The aim of this study was to investigate donor willingness compared to the continuously increasing demand in recent years. MATERIAL AND METHODS: Archives of the local eye bank at the Department of Ophthalmology, University of Cologne, Germany in the time period between 1 July 2011 and 31 December 2015 were examined regarding the willingness for corneal donations in deceased patients from the University Hospital of Cologne. Absolute numbers of deceased, exclusion criteria for donation as well as the rate of negative and affirmative decisions were evaluated. RESULTS: In 235 (5.1 %) out of 4593 deceased at the University Hospital of Cologne, corneal donation was accomplished during the observation period. Of the patients 2923 (63.6 %) were excluded because of absolute contraindications for corneal donation and the rate of absolute contraindications increased from 46.6 % in 2011 to 68.9 % in 2015. Willingness for corneal donation in potentially suitable deceased patients diminished from 34.9 % in 2011, to 34.3 % in 2012, 35.5 % in 2013, 28.4 % in 2014 and to 24.1 % in 2015. In relation to the total number of deceased, the number of corneal tissue donations decreased from 11.5 % in 2011 to 3.5 % in 2015. CONCLUSION: Despite a rising demand, data from Cologne seem to indicate that the number of corneal donations has declined to some extent. In order to increase the number of corneal donors in the future, further educational work as well as standardization and optimization of the tissue donation process seem to be urgently needed. PMID- 27260625 TI - [Central arterial occlusion after blunt force ocular injury : Case report]. AB - A healthy young male patient suffered a nearly complete loss of vision after a minor ocular injury. We describe a rare case of central arterial occlusion after blunt force trauma. After rheological therapy the visual acuity increased from perception of hand movement to 1/20, 1 month after the injury. Central artery occlusion is a rare but severe complication after blunt force ocular trauma that should be considered when patients suffer severe posttraumatic loss of vision. PMID- 27260626 TI - [Protection of corneal endothelium from apoptosis by gene and cell therapy]. AB - Protection of corneal endothelium from apoptosis using gene and cell therapy is in a translational phase. This approach offers advantages for eye banking and after transplantation. Safe vehicles for gene or cell therapeutic transduction of corneal endothelium with nucleic acids are available. This strategy will be further developed in consultation with the Paul Ehrlich Institute and European regulatory authorities. PMID- 27260627 TI - Associations of Body Mass Index and Physical Activity With Sexual Dysfunction in Breast Cancer Survivors. AB - Sexual dysfunction is a common and distressing consequence of breast cancer (BC) treatment. In the present study, we investigated the sexual functioning of BC patients and its association with women's personal characteristics and cancer treatments. In this cross-sectional study, sexual function was assessed using the Female Sexual Function Index (FSFI). The health-related quality of life (HRQOL) was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and its breast module BR-23. Of the 235 participants approached, 216 participants were included in the study. Of these, 63 patients reported no sexual activity in the last month and thus were analyzed only in relation to the sexual desire domain of FSFI. A total of 154 (71.3 %) patients were classified with hypoactive sexual desire disorder (HSDD). From those patients reporting sexual activity in the last month, 63.3 % (97 out of 153) were classified with sexual dysfunction. Using hierarchical logistic regression, the variance explained (change in R 2) by the addition of body mass index (BMI) and mild to moderate physical activity in the prediction models of sexual dysfunction and HSDD were 6.8 and 7.2 %, respectively. Age, BMI, and physical activity were independently associated with sexual dysfunction and HSDD. Additionally, BC patients with sexual dysfunction reported lower scores on global HRQOL, role functioning, and fatigue. Based on our findings, BC survivors should be encouraged to practice regular physical activity and to lose weight in order to avoid sexual dysfunction. However, future clinical trials are needed to confirm these findings. PMID- 27260628 TI - The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle. AB - It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, tubocurarine, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 MUM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, tubocurarine, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle. PMID- 27260629 TI - Future Research into C4 Biology. PMID- 27260631 TI - Severe liver disease as first sign of a haemophagocytic syndrome. PMID- 27260632 TI - Faecal calprotectin, an useful marker in discriminating between inflammatory bowel disease and functional gastrointestinal disorders. AB - INTRODUCTION: Diagnostic discrimination between inflammatory bowel disease (IBD) and functional gastrointestinal disorders is complex, as they cause similar signs and symptoms. Faecal calprotectin (FC) is a useful marker in this context, and can be used to select patients who will most benefit from colonoscopy. The aim of this study was to evaluate the utility of FC in discriminating between organic disease and functional disorders. MATERIAL AND METHODS: The study included 264 patients presenting with gastrointestinal complaints consistent with an organic pathology. FC levels were determined and diagnostic accuracy was assessed using the area under the curve obtained from the final diagnosis. RESULTS: Calprotectin levels in organic bowel disease patients were significantly higher (median 254MUg/g; 95% confidence interval [CI], interquartile range 105-588.5) than in functional disease patients (95MUg/g; 95% CI, 47.25-243.92) (P<.0001). Similarly, in patients with IBD, the values obtained were higher (270.85MUg/g; 95% CI, 96.85 674.00) than in those with irritable bowel syndrome (79.70MUg/g; 95% CI, 36.50 117.25) (P<.0001). For a cut-off of 150MUg/g, FC had an area under the ROC curve to discriminate between organic and functional disease of 0.718, and 0.872 to discriminate between irritable bowel syndrome and IBD. CONCLUSION: Our study supports the importance of FC as a marker in the evaluation of patients with IBD. The best diagnostic accuracy is obtained at a cut-off value of 150MUg/g. PMID- 27260633 TI - Capsule endoscopy: Diagnosis of lobular capillary haemangioma. PMID- 27260630 TI - Role of interleukin-6 in cancer progression and therapeutic resistance. AB - In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities. The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease. Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth. Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer. Its overexpression has been reported in almost all types of tumours. The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism. Moreover, IL 6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways. Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling. PMID- 27260634 TI - Colitis cystica profunda: A report of 2 cases with a 15-year follow-up. PMID- 27260635 TI - Sigma receptor type 1 knockout mice show a mild deficit in plasticity but no significant change in synaptic transmission in the CA1 region of the hippocampus. AB - The sigma-1 receptor (sigma-1R) is a chaperone protein located at the endoplasmic reticulum (ER) mitochondrial interface with roles in neuroprotection and cognition. Increasing evidence suggests that loss of sigma-1R function could contribute to neurological disease states making it a target for therapeutic intervention. Our objective was to elucidate the consequences to synaptic transmission and plasticity when sigma-1R is absent. We utilized a knockout mouse in which the gene encoding for sigma-1R was deleted (sigma-1R-KO mouse). Using whole-cell patch-clamp recordings from CA1 pyramidal neurons in the hippocampus, we examined neuronal excitability and glutamatergic synaptic function. Surprisingly, we detected no significant change in action potential firing and basic cellular characteristics. Furthermore, we found no significant change to pre-synaptic function as indicated by a similar paired-pulse ratio and miniature excitatory post-synaptic current frequency in sigma-1R-KO compared to wild-type (WT) mice. Similarly, the glutamate gated AMPA receptor and NMDA receptors were unaffected with no significant difference in AMPA/NMDA ratio or decay kinetics in sigma-1R-KO compared to WT mice. We further examined long-term potentiation in extracellular field recordings in CA1 stratum radiatum following Schaffer collateral stimulation. Interestingly, we found a small but significant reduction in the magnitude of long-term potentiation in mutant compared to WT mice. The results of this investigation suggest that basic cellular physiology is unaffected by sigma-1R loss, however the neuronal network is partially compromised. The sigma-1 receptor (sigma-1R) is a chaperone protein with roles in neuroprotection and cognition. We determined the consequences to synaptic transmission and plasticity when sigma-1R was absent. Utilizing the sigma-1R knockout mouse and electrophysiological recordings, we found no change in neuronal excitability and glutamatergic synaptic function. However, we found a significant reduction in long-term potentiation. PMID- 27260636 TI - High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde. AB - The transient receptor potential cation channel subfamily M 8 (TRPM8) agonist L menthol has been used traditionally for its topical counterirritant properties. Although the use of topical L-menthol for pain is casuistically established, evidence regarding its efficacy is negligible. This study aimed to characterize the effect of L-menthol as a counterirritant on cutaneous pain and hyperalgesia provoked by topical application of the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) agonist trans-cinnamaldehyde (CA). In a randomized, double-blinded study CA was applied to a 3 * 3-cm area of the volar forearm evoking neurogenic inflammation, pain, mechanical, and thermal hyperalgesia in 14 healthy volunteers. In different sessions, 10% CA alone or 40% L-menthol applied simultaneously with 10% CA were administered for 20 minutes, throughout which the subjects rated the pain intensity on a visual analogue scale of 0 to 10. Extensive quantitative sensory testing was conducted and superficial blood flow (neurogenic inflammation) was recorded. Administration of CA evoked spontaneous pain, neurogenic inflammation, thermal hyperalgesia, and primary and secondary mechanical hyperalgesia. Coadministration of topical L-menthol reduced spontaneous pain intensity (P < .01), neurogenic inflammation (P < .01), primary mechanical hyperalgesia (P < .05), secondary mechanical hyperalgesia (P < .05), and heat hyperalgesia (P < .05), but not cold hyperalgesia. L-menthol exhibited inhibitory effects on simultaneously established pain, hypersensitivity, and neurogenic inflammation in a human TRPA1-induced pain model. Potent TRPM8 agonists could be useful as topical antihyperalgesics. The study and the trial protocol is registered and approved by the local research ethics committee under the jurisdiction of the Danish Medicines Agency number N-20130005. The protocol also is registered at Clinicaltrials.gov under NCT02653703. PERSPECTIVE: Drugs interacting with transient receptor potential channels are of great therapeutic potential. In the present study we established cutaneous pain and hyperalgesia using the TRPA1 agonist CA. Subsequently, we showed that the frequently used topical counterirritant and TRPM8 agonist, L-menthol, decreased evoked pain, hyperalgesia, and inflammation, indicating direct and indirect antinociceptive mechanisms. PMID- 27260637 TI - Neural Correlates Differ in High and Low Fear-Avoidant Chronic Low Back Pain Patients When Imagining Back-Straining Movements. AB - The fear-avoidance model postulates that in an initial acute phase chronic low back pain (CLBP) patients acquire a fear of movement that results in avoidance of physical activity and contributes to the pain becoming chronic. The current functional magnetic resonance imaging study investigated the neural correlates of imagining back-straining and neutral movements in CLBP patients with high (HFA) and low fear avoidance (LFA) and healthy pain-free participants. Ninety-three persons (62 CLBP patients, 31 healthy controls; age 49.7 +/- 9.2 years) participated. The CLBP patients were divided into an HFA and an LFA group using the Tampa Scale of Kinesiophobia. The participants viewed pictures of back straining and neutral movements and were instructed to imagine that they themselves were executing the activity shown. When imagining back-straining movements, HFA patients as well as healthy controls showed stronger anterior hippocampus activity than LFA patients. The neural activations of HFA patients did not differ from those of healthy controls. This may indicate that imagining back-straining movements triggered pain-related evaluations in healthy controls and HFA participants, but not in LFA participants. Although heightened pain expectancy in HFA compared with LFA patients fits well with the fear-avoidance model, the difference between healthy controls and LFA patients was unexpected and contrary to the fear-avoidance model. Possibly, negative evaluations of the back-straining movements are common but the LFA patients use some kind of strategy enabling them to react differently to the back-straining events. PERSPECTIVE: It appears that low fear-avoidant back pain patients use some kind of strategy or underlying mechanism that enables them to react with less fear in the face of potentially painful movements. This warrants further investigation because countering fear and avoidance provide an important advantage with respect to disability. PMID- 27260638 TI - Repetitive Transcranial Magnetic Stimulation for Phantom Limb Pain in Land Mine Victims: A Double-Blinded, Randomized, Sham-Controlled Trial. AB - We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (-53.38 +/- 53.12% vs -22.93 +/- 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30-60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. PERSPECTIVE: High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions. PMID- 27260641 TI - Laparoscopic partial splenectomy: Surgical technique. PMID- 27260640 TI - Hospital care in severe trauma: Initial strategies and life-saving surgical procedures. AB - Severe trauma patients should be received at the hospital by a multidisciplinary team directed by a "trauma leader" and all institutions capable of receiving such patients should be well organized. As soon as the patient is accepted for care, the entire team should be prepared so that there is no interruption in the pre hospital chain of care. All caregivers should thoroughly understand the pre established protocols of diagnostic and therapeutic strategies to allow optimal management of unstable trauma victims in whom hemostasis must be obtained as soon as possible to decrease the morbid consequences of post-hemorrhagic shock. In patients with acute respiratory, circulatory or neurologic distress, several surgical procedures must be performed without delay by whichever surgeon is on call. Our goal is to describe these salvage procedures including invasive approaches to the upper respiratory tract, decompressive thoracostomy, hemostatic or resuscitative thoracotomy, hemostatic laparotomy, preperitoneal pelvic packing, external pelvic fixation by a pelvi-clamp, decompressive craniotomy. All of these procedures can be performed by all practitioners but they require polyvalent skills and training beforehand. PMID- 27260639 TI - Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol: a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults. AB - BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013. PMID- 27260642 TI - A cause of aerobilia without biliodigestive fistula: Acute cholecystitis with anaerobic gram-positive bacterial infection. PMID- 27260643 TI - Antiarrhythmic Drug Therapy for Rhythm Control in Atrial Fibrillation. AB - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and affects over 33 million people worldwide. AF is associated with stroke and systemic thromboembolism, unpleasant symptoms and reduced quality of life, heart failure, and increased mortality, and treatment of AF and its complications are associated with significant cost. Antiarrhythmic drugs (AADs) can suppress AF, allowing long-term maintenance of sinus rhythm, and have the potential to relieve symptoms and reverse or prevent adverse effects associated with AF. However, large randomized controlled studies evaluating use of AADs have not demonstrated a clear benefit to maintaining sinus rhythm, and AADs often have significant limitations, including a modest rate of overall success at maintaining sinus rhythm, frequent side effects, and potentially life-threatening toxicities. Although some of the currently available AADs have been available for almost 100 years, better tolerated and more efficacious AADs have recently been developed both for long-term maintenance of sinus rhythm and for chemical cardioversion of AF to sinus rhythm. Advances in automated AF detection with cardiac implantable electronic devices have suggested that AADs might be useful for suppressing AF to allow safe discontinuation of anticoagulation in select patients who are in sinus rhythm for prolonged periods of time. AADs may also have synergistic effects with catheter ablation of AF. This review summarizes the pharmacology and clinical use of currently available AADs for treatment of AF and discusses novel AADs and future directions for rhythm control in AF. PMID- 27260644 TI - Effect of everolimus initiation and early calcineurin inhibitor withdrawal on myocardial FOXP3+ regulatory T cells in heart transplantation. AB - BACKGROUND: Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels. METHODS: 15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n=8) withdrawal to conventional CNI based immunosuppression (Controls, n=7) after de novo HTx were included and FoxP3+ cells were quantified in 56 endomyocardial biopsies, and compared in the two patient groups. CAV was evaluated invasively using coronary intravascular ultrasound (IVUS). RESULTS: Baseline FoxP3 biopsy levels were similar in the two groups. The Everolimus group showed a significant increase in Foxp3 densities from baseline to time of one-year follow-up (median (IQR)=4.8*10(-7)(20.4) Tregs/MUm(2), P=0.046) while Controls showed no significant change (median (IQR)=3.1*10(-7)(6.5) Tregs/MUm(2), P=0.116). At 1-month follow-up FoxP3 densities correlated with the observed change in TAV from baseline to time of 1 year follow-up (r=0.641, P=0.034). FoxP3 densities at 1-week predicted acute cellular rejection (ACR) levels at 1month (P=0.026). No other correlations with ACR were found. CONCLUSION: Everolimus treatment combined with early CNI elimination is associated with increased densities of Tregs 12-months post-HTx compared to patients receiving CNI based regimen. Furthermore, the density of myocardial FoxP3+ cells early after transplantation appears to predict at least one measure of CAV burden after one year. PMID- 27260645 TI - Chromosomal phylogeny of Vampyressine bats (Chiroptera, Phyllostomidae) with description of two new sex chromosome systems. AB - BACKGROUND: The subtribe Vampyressina (sensu Baker et al. 2003) encompasses approximately 43 species and seven genera and is a recent and diversified group of New World leaf-nosed bats specialized in fruit eating. The systematics of this group continues to be debated mainly because of the lack of congruence between topologies generated by molecular and morphological data. We analyzed seven species of all genera of vampyressine bats by multidirectional chromosome painting, using whole-chromosome-painting probes from Carollia brevicauda and Phyllostomus hastatus. Phylogenetic analyses were performed using shared discrete chromosomal segments as characters and the Phylogenetic Analysis Using Parsimony (PAUP) software package, using Desmodontinae as outgroup. We also used the Tree Analysis Using New Technology (TNT) software. RESULTS: The result showed a well supported phylogeny congruent with molecular topologies regarding the sister taxa relationship of Vampyressa and Mesophylla genera, as well as the close relationship between the genus Chiroderma and Vampyriscus. CONCLUSIONS: Our results supported the hypothesis that all genera of this subtribe have compound sex chromosome systems that originated from an X-autosome translocation, an ancestral condition observed in the Stenodermatinae. Additional rearrangements occurred independently in the genus Vampyressa and Mesophylla yielding the X1X1X2X2/X1X2Y sex chromosome system. This work presents additional data supporting the hypothesis based on molecular studies regarding the polyphyly of the genus Vampyressa and its sister relationship to Mesophylla. PMID- 27260646 TI - Regional differences in oxidative metabolism and mitochondrial activity among cortical bone osteocytes. AB - Metabolic oxidative stress has been implicated as a cause of osteocyte apoptosis, an essential step in triggering bone remodeling. However, little is known about the oxidative behavior of osteocytes in vivo. We assessed the redox status and distribution of total and active mitochondria in osteocytes of mouse metatarsal cortical bone in situ. Multiphoton microscopy (MPM) was used to measure fluorescence of reduced pyridine nucleotides (NADH) under normoxic conditions and acutely following extreme (postmortem) hypoxic stress. Under non-hypoxic conditions, osteocytes exhibited no detectable fluorescence, indicating rapid NADH re-oxidation. With hypoxia, NADH levels peaked and returned to near baseline levels over 3h. Cells near the periosteal surface reached maximum NADH levels twice as rapidly as osteocytes near the mid-cortex, due to the time required to initiate NADH accumulation; once started, NADH accumulation followed a similar exponential relationship at all sites. Osteocytes near periosteal and endosteal bone surfaces also had higher mitochondrial content than those in mid-cortex based on immunohistochemical staining for mitochondrial ATPase-5A (Complex V ATPase). The content of active mitochondria, assessed in situ using the potentiometric dye TMRM, was also high in osteocytes near periosteum, but low in osteocytes near endocortical surfaces, similar to levels in mid-cortex. These results demonstrate that cortical osteocytes maintain normal oxidative status utilizing mainly aerobic (mitochondrial) pathways but respond to hypoxic stress differently depending on their location in the cortex, a difference linked to mitochondrial content. An apparently high proportion of poorly functional mitochondria in osteocytes near endocortical surfaces, where increased apoptosis mainly occurs in response to bone remodeling stimuli, further suggest that regional differences in oxidative function may in part determine osteocyte susceptibility to undergo apoptosis in response to stimuli that trigger bone remodeling. PMID- 27260647 TI - Seasonal changes in serum calcium, PTH and vitamin D levels in patients with primary hyperparathyroidism. AB - BACKGROUND: Seasonal variations of 25-hydroxyvitamin D, PTH and calcium levels are not well characterized in primary hyperparathyroidism (PHPT). Our objectives were to characterize seasonal changes in these parameters in PHPT patients, and to assess whether these seasonal changes affect clinical decision making. METHODS: This is a retrospective study based on the electronic medical records of Clalit Health service in the south of Israel between 2000 and 2012. Patients 18years and older with PHPT (PTH>upper limit of norm (ULN) and serum calcium>10.5mg%) were included. Patients with renal failure or on Thiazide diuretics were excluded. All serum levels of calcium, PTH and 25-hydroxyvitamin D were collected and then stratified according to season. RESULTS: 792 patients were classified as PHPT (72.2% female) and had a total of 2659 PTH tests, 1395 25 hydroxyvitamin D tests and 7426 calcium test. Fifty six percent of 25 hydroxyvitamin D levels were <50nmol/L. Seasonality was demonstrated in all three parameters: mean 25-hydroxyvitamin D was 13% higher in the summer compared to the winter (P<0.001), median PTH values showed opposite trend with a fall of about 8.4% in summer compared to winter (P<0.001). Calcium levels were higher during the autumn with a rise of about 0.2mg/dL in the mean calcium levels compared to spring and summer (P<0.001). The odds ratio of calcium level above 11.5mg/dL is highest in the autumn (OR=1.275, P=0.018). CONCLUSION: We show seasonal variation in serum 25-hydroxyvitamin D, PTH, and calcium levels in patients with PHPT. These seasonal variations cause transition to pathological values that may influence diagnosis and treatment of PHPT patients. PMID- 27260648 TI - Letter to the Editor, concerning: "FGF23-regulated production of fetuin-A (AHSG) in osteocytes". PMID- 27260649 TI - Covering bariatric surgery has minimal effect on insurance premium costs within the Affordable Care Act. AB - BACKGROUND: Currently, of the 51 state health exchanges operating under the Affordable Care Act, only 23 include benchmark plans that cover bariatric surgery coverage. Bariatric surgery coverage is not considered an essential health benefit in 28 state exchanges, and this lack of coverage has a discriminatory and detrimental impact on millions of Americans participating in state exchanges that do not provide bariatric surgery coverage. OBJECTIVES: We examined 3 state exchanges in which a portion of their plans provided coverage for bariatric surgery to determine if bariatric surgery coverage is correlated with premium costs. SETTING: State health exchanges; United States. METHODS: Data from the 2015 state exchange plans were analyzed using information from the Centers for Medicare & Medicaid Services' Individual Market Landscape file and Benefits and Cost Sharing public use files. RESULTS: Only 3 states (Oklahoma, Oregon, and Virginia) in the analysis have 1 or more rating regions in which a portion of the plans cover bariatric surgery. In Oklahoma and Oregon, the average monthly premiums for all bronze, silver, and gold coverage levels are higher for plans covering bariatric surgery. Only 1 of these states included platinum plans that cover bariatric surgery. The average difference in premiums was between $1 to $45 higher in Oklahoma, and $18 to $32 higher in Oregon. Conversely, in Virginia, the average monthly premiums are between $2 and $21 lower for each level for plans covering bariatric surgery. Monthly premiums for plans covering versus not covering bariatric surgery ranged from 6% lower to 15% higher in the same geographic rating region. CONCLUSIONS: Across all 3 states in the sample, the average monthly premiums do not differ consistently on the basis of whether the state exchange plans cover bariatric surgery. PMID- 27260650 TI - Effect of different bariatric surgery type on the leukocyte formula. AB - BACKGROUND: Obesity is associated with higher leukocyte counts, whereas weight loss decreases these counts. It is unknown if different bariatric surgery (BS) types have different effects on leukocytes. OBJECTIVES: The aim of the study was to determine predictors of leukocyte and their subset count variation in patients submitted to BS. SETTING: Tertiary care university hospital, Porto, Portugal. METHODS: This was a retrospective analysis of patients submitted to Roux-en-Y gastric bypass (RYGB), laparoscopic adjustable gastric banding (LAGB), or sleeve gastrectomy (SG). Leukocyte and subset counts were compared between baseline and 1-year postsurgery and between BS types. A multivariate linear regression model was built to study determinants of leukocyte and subset variation. RESULTS: We analyzed 764 patients: 238 submitted to LAGB; 452 to RYGB, and 74 to SG. Mean age was 42 years and 86.6% were women. All BS types were associated with a decrease in leukocyte and neutrophil counts but the variation in body mass index and homeostatic model assessment (HOMA-IR) were the only variables independently associated with a decrease 1-year postsurgery. Monocytes increased in patients submitted to LAGB and decreased in those who underwent RYGB and SG. The BS type was independently associated with monocyte variation. Patients who underwent RYGB and SG had a decrease in monocyte counts of 77/uL and 62/uL, respectively, compared with LAGB. CONCLUSION: Weight and insulin resistance are the main predictors of leukocyte and neutrophil variation after BS. The specific type of BS is a determinant of monocyte count variation independent of the amount of weight loss or the degree of insulin resistance improvement. PMID- 27260651 TI - Roux-en-Y gastric bypass reversal: a systematic review. AB - BACKGROUND: Due to the large number of Roux-en-Y gastric bypass surgeries performed over the last decade, reversal of the bypass to normal anatomy has been increasingly reported. SETTING: University affiliated Teaching Hospital, United States. OBJECTIVES: The aim of this systematic review was to summarize the literature data regarding the indications, technical considerations, and outcomes of gastric bypass reversal. METHODS: PubMed/MEDLINE search was conducted for articles reporting reversal of gastric bypass to normal anatomy. Patients' demographic characteristics, primary reason for reversal, reversal technique, and postreversal events were retrieved and categorized from each eligible paper. RESULTS: Thirty-five articles encompassing a total of 100 patients were eligible. Malnutrition was the most common indication for reversal (12.3%), followed by severe dumping syndrome (9.4%), postprandial hypoglycemia (8.5%), and excessive weight loss (8.5%). Techniques for gastrogastrostomy were available in 42 patients, with the hand-sewn technique as the most common (67.4%) followed by the linear stapler (23.2%) and the end-to-end anastomosis stapler used in 3 patients (6.9%). The reversal technique was performed endoscopically and described in 3 studies (3 patients). Techniques for handling the Roux limb were described in 56 patients (56%); the limb was reconnected in 32 patients (57.2%) and resected in 24 patients (42.8%). Weight regain was the most prevalent postreversal event (28.8%), followed by severe gastroesophageal reflux diseases (10.2%) and persistent abdominal pain (6.8%). There was no reported mortality. CONCLUSION: Gastric bypass reversal is indicated for excessive weight loss, dumping syndrome, and postprandial hypoglycemia. The procedure is well tolerated and feasible when performed laparoscopically and has no reported mortality. PMID- 27260652 TI - Surgery for type 2 diabetes: the case for Roux-en-Y gastric bypass. AB - The Roux-en-Y gastric bypass (RYGB) has traditionally been the most common bariatric procedure. Long-term data on the efficacy of RYGB demonstrate a long lasting benefit in weight loss and control of the metabolic syndrome. Although observations of type 2 diabetes (T2D) resolution after RYGB have been reported for 3 decades, it was not until recently that multiple randomized trials comparing RYGB to medical therapy verified the same thing: RYGB leads to significantly greater diabetes control and remission. Even though T2D can relapse, there remains a significant overall benefit of bariatric surgery regarding the downstream effects of T2D: cardiovascular risk and micro- and macrovascular complications. Limited data are available on the comparative effectiveness of RYGB and sleeve gastrectomy in improving glucose homeostasis, but studies including both surgical procedures suggest that the benefit of RYGB in T2D may be more profound. Although further research is needed to examine closely any differences between these 2 procedures, multiple studies underscore the unprecedented value of bariatric surgery for the control and remission of T2D. PMID- 27260653 TI - Osteoarthritis in veterans undergoing bariatric surgery is associated with decreased excess weight loss: 5-year outcomes. AB - BACKGROUND: Obesity exacerbates pre-existing musculoskeletal disease and joint pain. This may limit physical activity in obese individuals. OBJECTIVES: We sought to identify the disease burden and impact of osteoarthritis of the lumbar back, hip, knee, and ankle in veterans undergoing bariatric surgery. SETTING: Veterans Affairs medical center. METHODS: Retrospective review of a prospective bariatric database of operations performed at a single Veterans Affairs medical center. Patients with osteoarthritis of the lumbar spine, hip, knee, or ankle were identified and diagnosis confirmed by electronic health record review of prior radiographic reports. Analysis was performed using chi2 test for continuous variables. Student's t test and one-way analysis of variance were used to compare qualitative variables. RESULTS: Of 254 bariatric surgical patients, 83.9% had preoperative musculoskeletal pain before bariatric surgery and 59.1% had a confirmed diagnosis of osteoarthritis of the lumbar spine, hips, knees, and/or ankles. Follow-up rate was 97.4%, 85.4%, and 82.6% at 1, 3, and 5 years respectively. Of patients with osteoarthritis, 58.6% had knee involvement and 46% had multiple sites involved. In the cohort without osteoarthritis, percent excess body mass index loss was 66.9% at 1 year versus 58.5% in the cohort with osteoarthritis (P = .009), 66.1% versus 51.9% (P = .001) at 3 years, and 64.3% versus 50.1% (P = .002) after 5 years. Percent total weight loss was 28.4% versus 25.2%, 28.0% versus 22.8%, and 27.1% versus 22.4%, respectively, at 1, 3, and 5 years. CONCLUSIONS: Osteoarthritis is common among veterans undergoing bariatric surgery. It is associated with significantly less weight loss compared to veterans who do not have osteoarthritis, up to 5 years after bariatric surgery. PMID- 27260654 TI - One-stage conversion of Roux-en-Y gastric bypass to a modified biliopancreatic diversion with duodenal switch using a hybrid sleeve concept. AB - BACKGROUND: Insufficient weight loss (percentage of excess weight loss [%EWL]<50%) is observed in approximately 20% of patients after Roux-en-Y gastric bypass (RYGB). Surgical revision can be performed by various procedures including malabsorptive techniques. Conversion to a biliopancreatic diversion with duodenal switch (BPD/DS) remains a complex technique which cannot always be performed as a one-stage procedure. OBJECTIVES: This study evaluates the conversion of RYGB to BPD/DS using a novel gastric reconstruction technique based on a "hybrid sleeve" using the existing gastrojejunal anastomosis of the RYGB. SETTING: All the procedures were performed at a private hospital. METHODS: The consecutive patients who were eligible for conversion since 2010 were reviewed; eligibility included %EWL<=50% and normal gastric pouch. The gastrojejunal anastomosis of the RYGB was untouched and the gastric fundus was resected. The gastric continuity was restored by an anastomosis between a short segment of the alimentary limb and the gastric antrum. A standard BPD/DS was then performed without restoration of the jejunal continuity. RESULTS: Fourteen patients were converted to BPD/DS for a mean body mass index (BMI) of 44.3+/-6.0 kg/m2, a mean %EWL of 33.4%, and a percentage of total weight loss (%TWL) of 15.3+/-11.7%. The BMI before RYGB was 54.4+/-13.1 kg/m2, with half of the patients being super-obese. All but 3 conversions were completed as a single stage and laparoscopically in a mean of 177 minutes. The 30-day complication rate was 28.5%. No patient was lost to follow-up over a mean 25.8 months and the BMI of the 12 patients with a follow up>=3 months is 33.2+/-7.2 kg/m2. With reference to the initial weight of the patients, the mean %EWL is 73.5% and %TWL is 37.6+/-16.0%. On average, patients benefited from a 21.1% TWL through the conversion of their RYGB. CONCLUSIONS: This procedure allows for an easier conversion of RYGB to BPD/DS and appears to be the most effective procedure for resuming weight loss. Nutritional consequences and weight loss are similar to the primary BPD/DS results. However, the benefits and risks must be carefully assessed according to the definition of weight loss failure. PMID- 27260655 TI - A balanced translocation disrupting BCL2L10 and PNLDC1 segregates with affective psychosis. AB - Affective psychoses are a group of severe psychiatric disorders, including schizoaffective disorder and bipolar I disorder, together affecting ~1% of the population. Despite their high heritability, the molecular genetics and neurobiology of affective psychosis remain largely elusive. Here, we describe the identification of a structural genetic variant segregating with affective psychosis in a family with multiple members suffering from bipolar I disorder or schizoaffective disorder, bipolar type. A balanced translocation involving chromosomes 6 and 15 was detected by karyotyping and fluorescence in-situ hybridization (FISH). Using whole-genome sequencing, we rapidly delineated the translocation breakpoints as corresponding intragenic events disrupting BCL2L10 and PNLDC1. These data warrant further consideration for BCL2L10 and PNLDC1 as novel candidates for affective psychosis. (c) 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID- 27260656 TI - Immunotherapy of Brain Cancer. AB - The brain has long been considered an immune-privileged site precluding potent immune responses. Nevertheless, because of the failure of conventional anti cancer treatments to achieve sustained control of intracranial neoplasms, immunotherapy has been considered as a promising strategy for decades. However, several efforts aimed at exploiting the immune system as a therapeutic weapon were largely unsuccessful. The situation only changed with the introduction of the checkpoint inhibitors, which target immune cell receptors that interfere with the activation of immune effector cells. Following the observation of striking effects of drugs that target CTLA-4 or PD-1 against melanoma and other tumor entities, it was recognized that these drugs may also be active against metastatic tumor lesions in the brain. Their therapeutic activity against primary brain tumors is currently being investigated within clinical trials. In parallel, other immunotherapeutics such as peptide vaccines are at an advanced stage of clinical development. Further immunotherapeutic strategies currently under investigation comprise adoptive immune cell transfer as well as inhibitors of metabolic pathways involved in the local immunosuppression frequently found in brain tumors. Thus, the ongoing implementation of immunotherapeutic concepts into clinical routine may represent a powerful addition to the therapeutic arsenal against various brain tumors. PMID- 27260657 TI - Rapid detection of lineage IV peste des petits ruminants virus by real-time RT PCR. AB - Peste des petits ruminants virus (PPRV) is the cause agent of peste des petitis ruminants (PPR). A novel lineage IV PPRV has reemerged in China in 2013 and 2014. Mass vaccination was implemented in most provinces in China. In order to detect lineage IV PPRV in clinical samples and to distinguish rapidly it from the other lineages PPRVs, a real-time RT-PCR assay was developed. This assay showed high sensitivity, specificity and efficiency in differentiating the lineage IV PPRV from others. The performance of this assay was evaluated by positive clinical samples of lineage IV viruses. This new real-time RT-PCR assay will facilitate epidemiological investigations and rapid differentiatial diagnosis in areas where lineage IV viruses are circulating. PMID- 27260658 TI - Detection and transmission of Carrot torrado virus, a novel putative member of the Torradovirus genus. AB - A new Torradovirus tentatively named Carrot torrado virus (CaTV) was an incidental finding following a next generation sequencing study investigating internal vascular necrosis in carrot. The closest related viruses are Lettuce necrotic leaf curl virus (LNLCV) found in the Netherlands in 2011 and Motherwort yellow mottle virus (MYMoV) found in Korea in 2014. Primers for reverse transcriptase-PCR (RT-PCR) and RT-qPCR were designed with the aim of testing for the presence of virus in plant samples collected from the field. Both methods successfully amplified the target from infected samples but not from healthy control samples. The specificity of the CaTV assay was also checked against other known carrot viruses and no cross-reaction was seen. A comparative study between methods showed RT-qPCR was the most reliable method, giving positive results in samples where RT-PCR fails. Evaluation of the Ct values following RT-qPCR and a direct comparison demonstrated this was due to improved sensitivity. The previous published Torradovirus genus specific RT-PCR primers were tested and shown to detect CaTV. Also, virus transmission experiments carried out suggest that unlike other species of the same genus, Carrot torrado virus could be aphid-transmitted. PMID- 27260659 TI - A young male with more than lupus. PMID- 27260660 TI - ThrR, a DNA-binding transcription factor involved in controlling threonine biosynthesis in Bacillus subtilis. AB - The threonine dehydratase IlvA is part of the isoleucine biosynthesis pathway in the Gram-positive model bacterium Bacillus subtilis. Consequently, deletion of ilvA causes isoleucine auxotrophy. It has been reported that ilvA pseudo revertants having a derepressed hom-thrCB operon appear in the presence of threonine. Here we have characterized two classes of ilvA pseudo-revertants. In the first class the hom-thrCB operon was derepressed unmasking the threonine dehydratase activity of the threonine synthase ThrC. In the second class of mutants, threonine biosynthesis was more broadly affected. The first class of ilvA pseudo-revertants had a mutation in the Phom promoter (P*hom ), resulting in constitutive expression of the hom-thrCB operon. In the second class of ilvA pseudo-revertants, the thrR gene encoding a putative DNA-binding protein was inactivated, also resulting in constitutive expression of the hom-thrCB operon. Here we demonstrate that ThrR is indeed a DNA-binding transcription factor that regulates the hom-thrCB operon and the thrD aspartokinase gene. DNA binding assays uncovered the DNA-binding site of ThrR and revealed that the repressor competes with the RNA polymerase for DNA binding. This study also revealed that ThrR orthologs are ubiquitous in genomes from the Gram-positive phylum Firmicutes and in some Gram-negative bacteria. PMID- 27260661 TI - Can only one person be right? The development of objectivism and social preferences regarding widely shared and controversial moral beliefs. AB - Prior work has established that children and adults distinguish moral norms (e.g., hitting is wrong) from conventional norms (e.g., wearing pajamas to school is wrong). Specifically, moral norms are generally perceived as universal across time and space, similar to objective facts. We examined preschoolers' and adults' perceptions of moral beliefs alongside facts and opinions by asking whether only one person could be right in the case of disagreements. We also compared perceptions of widely shared moral beliefs (e.g., whether it is better to pull someone's hair or share with someone) and controversial moral beliefs (e.g., whether it is better to help someone with a project or make cookies for someone). In Studies 1 and 2, preschoolers and adults were more likely to judge that only one person could be right in the case of widely shared versus controversial moral beliefs, treating the former as more objective or fact-like. Children were also more likely than adults to say that only one person could be right in a moral disagreement. Study 2 additionally revealed that adults were more likely than children to report preferring individuals who shared their controversial moral beliefs. Study 3 replicated these patterns using a different sample of widely shared beliefs (e.g., whether it is okay to mock a poor classmate) and controversial moral beliefs (e.g., whether it is okay to tell small, prosocial lies). While some aspects of moral cognition may depend on abundant social learning and cognitive development, the perception that disagreements about widely shared moral beliefs have only one right answer while disagreements about controversial moral beliefs do not emerges relatively early. We discuss implications for moral learning and social preferences. PMID- 27260662 TI - Characterization, kinetics and thermodynamics of Ag(I) sorption using novel sorbent: Dry wheatgrass. AB - In the present study, dried wheatgrass (DWG), an available and renewable biomass, was investigated as a novel Ag(I) sorbent. Sorption data was modeled to 11 different kinetic and diffusion models at different DWG concentration. Pseudo second-order model fits the data most appropriately among these. Diffusion was not the sole mechanism controlling Ag(I) sorption by DWG. The enthalpy and entropy for Ag(I) sorption by DWG are 10.511 kJ mol(-1) and 0.065 kJ mol(-1) K( 1), respectively. Gibbs free energy decreases with rise in temperature. Ag(I) sorption by DWG is spontaneous, endothermic with increased randomness at the interface. Characterization of DWG suggested the presence of diverse functional groups. Ag(I) sorption by DWG involved mechanisms such as physisorption and chemisorptions. DWG can be efficiently used to remediate and recover Ag(I) from solution in an eco-friendly manner. PMID- 27260663 TI - Earmarking and the political support of fat taxes. AB - An unhealthy good causes health issues in the long run. It creates a misperceived utility loss and increases health care costs. Conversely, a healthy good provides misperceived utility gains and reduces health care costs. Individuals differ in income and in their degree of misperception; they vote over a fat tax according to their misperceived utility. A fraction of the tax proceeds is "earmarked" to reduce health insurance premiums; the remainder finances a subsidy on the healthy good. This earmarking rule is determined to maximize welfare, anticipating the induced political equilibrium. The equilibrium fat tax is always lower than the utilitarian level. This is not necessarily true with a Rawlsian objective. The determination of the earmarking rule is complex. Even in the utilitarian case, it is not just used to boost political support for the fat tax. Instead, it may involve a tradeoff between fat tax and healthy good subsidy. PMID- 27260664 TI - Denoising of MR spectroscopic imaging data using statistical selection of principal components. AB - OBJECTIVES: To evaluate a new denoising method for MR spectroscopic imaging (MRSI) data based on selection of signal-related principal components (SSPCs) from principal components analysis (PCA). MATERIALS AND METHODS: A PCA-based method was implemented for selection of signal-related PCs and denoising achieved by reconstructing the original data set utilizing only these PCs. Performance was evaluated using simulated MRSI data and two volumetric in vivo MRSIs of human brain, from a normal subject and a patient with a brain tumor, using variable signal-to-noise ratios (SNRs), metabolite peak areas, Cramer-Rao bounds (CRBs) of fitted metabolite peak areas and metabolite linewidth. RESULTS: In simulated data, SSPC determined the correct number of signal-related PCs. For in vivo studies, the SSPC denoising resulted in improved SNRs and reduced metabolite quantification uncertainty compared to the original data and two other methods for denoising. The method also performed very well in preserving the spectral linewidth and peak areas. However, this method performs better for regions that have larger numbers of similar spectra. CONCLUSION: The proposed SSPC denoising improved the SNR and metabolite quantification uncertainty in MRSI, with minimal compromise of the spectral information, and can result in increased accuracy. PMID- 27260665 TI - The use of DNA barcode for identifying species of Oxysarcodexia Townsend (Diptera: Sarcophagidae): A preliminary survey. AB - Oxysarcodexia is one of the Neotropical richest genera within the Sarcophagidae family. Medical, veterinary and forensic importance of these flies are due to their association with corpses, cases of myiasis in humans and domestic animals, and being pathogen carriers. Regarding morphological identification, molecular techniques, especially the DNA-based ones, arise as useful alternatives or complementary methodologies for species identification. Thus, in this study we aimed to investigate the potential of the COI marker (barcode region) to delimit Oxysarcodexia species in comparison with the morphological identification criteria. A COI fragment was amplified and the length of the sequences after alignment were of 648bp (149 parsimoniously informative variable sites). According to the Neighbor-Joining phylogenetic tree, specimens of the same morphological species were clustered in monophyletic clades (82-100% bootstrap branch support). Species-level resolution thus achieved was successful, despite low interspecific divergence (1.8-2.3%) and since interspecific variation was higher than intraspecific divergence (0.1-1.2%). Therefore, the use of COI barcode sequences supports differentiation and identification of the Oxysarcodexia species studied. PMID- 27260666 TI - An overview on different aspects of hypodermosis: Current status and future prospects. AB - Livestock plays a vital role in economic development of a nation and is being used in agriculture for draft power, production of farmyard manure as well as milk and meat production. Bovine hypodermosis is the top culprit among all parasitic infections across the world. Hypodermosis is an endemic disease in the mountainous areas/plain areas and is regularly observed in the northern hemisphere of the globe affecting cattle, deer, yaks and buffaloes. There is a wide variation in geographical distribution of Hypoderma spp. during the years 1945-2015. The manuscript includes a geospatial study that tries to maps the global distribution of hypodermosis in different areas of the world in order to detect hotspots or endemic areas that may be a potential source for disease spread. This information's are very useful to predict the potential high risk areas that are prone to disease outbreak. The present review aims to evaluate the global distribution, molecular discrimination, diagnostics and vaccination of hypodermosis, focusing on its current status and future perspectives towards the management of the disease and its control strategies. PMID- 27260667 TI - Prevalence, risk factors and molecular characterization of Enterocytozoon bieneusi in raccoon dogs (Nyctereutes procyonoides) in five provinces of Northern China. AB - The disease microsporidiosis is found worldwide and is mainly caused by Enterocytozoon bieneusi. E. bieneusi can infect a wide range of hosts; however, information regarding the prevalence and genotyping of E. bieneusi infection in raccoon dogs (Nyctereutes procyonoides) is limited. Therefore, in 2015, we examined 305 faecel samples from 80 farmed raccoon dogs in Jilin Province, from 54 in Hebei Province, from 72 in Liaoning Province, from 29 in Shandong Province, and from 40 in Heilongjiang Province. The overall prevalence of E. bieneusi infection in farmed raccoon dogs was 22.30%. Logistic regression analysis suggests that age, gender and region of raccoon dogs were highly related to the prevalence of E. bieneusi infection. Moreover, six E. bieneusi internal transcribed spacer (ITS) region sequences, including four known genotypes, namely D, CHN-DC1, NCF2, and CHN-F1, and two novel genotypes (NCR1 and NCR2), were identified in the present study. The present study firstly indicated the existence of E. bieneusi genotypes NCF2, NCR1, NCR2and CHN-F1 in infected raccoon dogs in Northern China. Integrated control strategies should be implemented to limit E. bieneusi infection in farmed raccoon dogs, and to prevent transmission of this disease to other animals and humans. PMID- 27260668 TI - Vector competence of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) for the DEN2-FJ10 and DEN2-FJ11 strains of the dengue 2 virus in Fujian, China. AB - Dengue is an acute, emerging, infectious disease transmitted by Aedes mosquitoes that has become a serious global public health problem. The DEN2-FJ10 and DEN2 FJ11 strains of the dengue 2 virus were originally isolated from the serum of a patient with dengue fever in Fujian Province, China, in 1999. Our data provide the first assessment of the vector competence of Aedes mosquitoes with respect to the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus. There were significant differences in the replication rates of these two viral strains in Aedes albopictus and Aedes aegypti (P<0.05); replication of the DEN2-FJ10 strain was greater in Ae. aegypti than in Ae. albopictus 5 days post infection whereas replication of the DEN2-FJ11 was greater in Ae. albopictus than in Ae. aegypti 7 days post infection. The replicative ability of the DEN2-FJ11 strain was greater than that of the DEN2-FJ10 strain in infected Ae. albopictus. In infected Ae. aegypti, rapid proliferation of the DEN2-FJ10 strain occurred earlier than in the DEN2-FJ11 strain. There were no significant differences in the midgut and salivary gland infection rates of Ae. albopictus and Ae. aegypti with respect to either viral strain. Although the DEN2-FJ10 and DEN2-FJ11 strains differ in their virulence to neonatal rats, there was no significant difference in the ability of either Ae. albopictus or Ae. aegypti to transmit the DEN2-FJ10 and DEN2-FJ10 strains of the dengue 2 virus (P>0.05). In summary, our results indicate that Ae. albopictus and Ae. aegypti mosquitoes are moderately competent vectors of the DEN2-FJ10 and DEN2-FJ11 strains of the dengue virus and provide the first evidence of the effect of these two viral strains on the vector competence of mosquitoes in China. PMID- 27260669 TI - Does MW Radiation Affect Gene Expression, Apoptotic Level, and Cell Cycle Progression of Human SH-SY5Y Neuroblastoma Cells? AB - Neuroblastoma (NB) is a cancer that occurs in sympathetic nervous system arising from neuroblasts and nerve tissue of the adrenal gland, neck, chest, or spinal cord. It is an embryonal malignancy and affects infants and children. In this study, we investigated the effects of microwave (MW) radiation on apoptotic activity, cell viability, and cell cycle progression in human SH-SY5Y NB cells which can give information about MW radiation effects on neural cells covering the period from the embryonic stages to infants. SH-SY5Y NB cells were exposed to 2.1 GHz W-CDMA modulated MW radiation for 24 h at a specific absorption rate of 0.491 W/kg. Control samples were in the same conditions with MW-exposed samples but they were not exposed to MW radiation. The apoptotic activity of cells was measured by Annexin-V-FITC and propidium iodide staining. Moreover, mRNA levels of proliferative and cell cycle proteins were determined by real-time RT-PCR. The change in cell cycle progression was observed by using CycleTest-Plus DNA reagent. No significant change was observed in apoptotic activity of MW-exposed cells compared to control cells. The mRNA levels of c-myc and cyclin D1 were significantly reduced in MW group (p < 0.05). The percentage of MW-exposed cells in G1 phase was significantly higher than the percentage of control cells in G1 phase. MW radiation caused cell cycle arrest in G1 phase. These results showed that 2.1 GHz W-CDMA modulated MW radiation did not cause apoptotic cell death but changed cell cycle progression. PMID- 27260670 TI - Inconsistency in the Self-report of Chronic Diseases in Panel Surveys: Developing an Adjudication Method for the Health and Retirement Study. AB - Objectives: Chronic disease data from longitudinal health interview surveys are frequently used in epidemiologic studies. These data may be limited by inconsistencies in self-report by respondents across waves. We examined disease inconsistencies in the Health and Retirement Study and investigated a multistep method of adjudication. We hypothesized a greater likelihood of inconsistences among respondents with cognitive impairment, of underrepresented race/ethnic groups, having lower education, or having less income/wealth. Method: We analyzed Waves 1995-2010, including adults 51 years and older (N = 24,156). Diseases included hypertension, heart disease, lung disease, diabetes, cancer, stroke, and arthritis. We used questions about the diseases to formulate a multistep adjudication method to resolve inconsistencies across waves. Results: Thirty percent had inconsistency in their self-report of diseases across waves, with cognitive impairment, proxy status, age, Hispanic ethnicity, and wealth as key predictors. Arthritis and hypertension had the most frequent inconsistencies; stroke and cancer, the fewest. Using a stepwise method, we adjudicated 60%-75% of inconsistent responses. Discussion: Discrepancies in the self-report of diseases across multiple waves of health interview surveys are common. Differences in prevalence between original and adjudicated data may be substantial for some diseases and for some groups, (e.g., the cognitively impaired). PMID- 27260671 TI - The Good Clinical Practice guideline and its interpretation - perceptions of clinical trial teams in sub-Saharan Africa. AB - OBJECTIVES: To explore the advantages and challenges of working with the Good Clinical Practice (GCP)-International Conference of Harmonization (ICH) E6 guideline and its interpretation from the perspective of clinical trial teams based in sub-Saharan Africa. METHODS: We conducted 60 key informant interviews with clinical trial staff at different levels in clinical research centres in Kenya, Ghana, Burkina Faso and Senegal and thematically analysed the responses. RESULTS: Clinical trial teams perceived working with ICH-GCP as highly advantageous and regarded ICH-GCP as applicable to their setting and efficiently applied. Only for informed consent did some clinical trial staff (one-third) perceive the guideline as insufficiently applicable. Specific challenges included meeting the requirements for written and individual consent, conditions for impartial witnesses for illiterates or legally acceptable representatives for children, guaranteeing voluntary participation and ensuring full understanding of the consent given. It was deemed important to have ICH-GCP compliance monitored by relevant ethics committees and regulatory authorities, without having guidelines applied overcautiously. CONCLUSION: Clinical trial teams in sub Saharan Africa perceived GCP as a helpful guideline, despite having been developed by northern organisations and despite the high administrative burden of implementing it. To mitigate consent challenges, we suggest adapting GCP and making use of the flexibility it offers. PMID- 27260672 TI - Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock. AB - LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10mg/kg) or DEX (5mg/kg) at 1 and 12h before injecting LPS (30mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-alpha, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-alpha, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway. PMID- 27260673 TI - Inhibition by ketamine and amphetamine analogs of the neurogenic nitrergic vasodilations in porcine basilar arteries. AB - The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100MUM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing alpha3beta2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation and, possibly, normal blood flow in the brainstem. PMID- 27260674 TI - Mitragynine and its potential blocking effects on specific cardiac potassium channels. AB - Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, IK1, a Kir current mediated by Kir2.1 channel and IKACh, a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC50 value of 1.62MUM and 1.15MUM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit IKACh current with an IC50 value of 3.32MUM but has no significant effects on IK1. Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks. PMID- 27260675 TI - Investigation of Kudoa yasunagai (Hsieh & Chen, 1984) infection kinetics in Seriola lalandi (Valenciennes, 1833) by quantitative PCR. PMID- 27260676 TI - Exploring the N-terminal role of a heterologous protein in secreting out of Escherichia coli. AB - Escherichia coli is commonly used as a host for the extracellular production of proteins. However, its secretion capacity is often limited to a frustratingly low level compared with other expression hosts, because E. coli has a complex cell envelope with two layers. In previous report, we identified that the catalytic domain of a cellulase (Cel-CD) from Bacillus subtilis can be secreted into the medium from recombinant E. coli in large quantities without its native signal peptide. In this study, we proved the N-terminal sequence of the full length Cel CD played a crucial role in transportation through both inner and outer membranes. By subcellular location analysis, we verified that the secretion was a two-step process via the SecB-dependent pathway through the inner membrane and an unknown pathway through the outer membrane. However, the N-terminal region of Cel CD is polar and hydrophilic, which showed no similarities to other typical signal sequences. Random mutagenesis experiment suggested that the N-terminal sequence is a compromising result of transportation through inner and outer membranes. This is the first report that a "non-classical signal peptide" can guide recombinant proteins out of the cells from cytoplasm. Biotechnol. Bioeng. 2016;113: 2561-2567. (c) 2016 Wiley Periodicals, Inc. PMID- 27260677 TI - Consensus on Recording Deep Endometriosis Surgery: the CORDES statement. PMID- 27260678 TI - Plantar heel pain. PMID- 27260679 TI - Population pharmacokinetics of arbekacin in different infectious disease settings and evaluation of dosing regimens. AB - The efficacy of arbekacin in patients with MRSA infections is influenced by the peak concentration (Cpeak)/MIC ratio (?8). A daily arbekacin dose of 4-6 mg/kg is primarily used for the treatment of MRSA infection. However, clinical pharmacokinetic studies of arbekacin that evaluate changes in patients with different infectious diseases have been limited. This study was to evaluate the pharmacokinetics of arbekacin in different infectious diseases and to evaluate its dosing regimens. This work describes a single-centre, retrospective study. The pharmacokinetic parameters of arbekacin were calculated from individual serum concentration data using WinNonlin ver. 6.3. A total of 331 serum samples were obtained from 170 patients. Our drug concentration-time data were well described by a two-compartment open model. The final model showed that drug clearance was related to creatinine clearance and that the total distribution volume (Vd) was related to actual body weight and the presence of bacteremia. The individual Vd in bacteremia patients was significantly higher than those of other patients (bacteremia: 29.7 +/- 0.5 L, pneumonia: 20.8 +/- 0.4 L, other infections: 21.4 +/ 0.4 L; p < 0.05). Additionally, Monte Carlo simulation showed that target (Cpeak/MIC ? 8) attainment was only 10.1%, even at a dose of 6 mg/kg, especially for MRSA bacteremia patients with an arbekacin MIC = 2 MUg/mL. In conclusion, our study revealed that the Vd may be higher in bacteremia patients than in patients with other infectious diseases. Therefore, an increase in the daily dose of arbekacin should be considered for bacteremia patients. PMID- 27260680 TI - Characterization of assortative mating in medaka: Mate discrimination cues and factors that bias sexual preference. AB - Somatolactin alpha (SLalpha) is a peptide hormone that regulates skin color, and SLalpha-deficient and SLalpha-excess strains have been established in medaka (Oryzias latipes). Their skin colors differ conspicuously and males prefer to mate with females from the same strain. Pre-mating sexual isolation in this model vertebrate provides an ideal platform for investigating the molecular mechanisms of mate choice. Thus, we studied the sensory cues utilized by these fish to discriminate the same and different strains. When males were given a choice under monochromatic light, where the skin colors differed only in terms of brightness but not in hue, mating occurred but it was not assortative. This suggests that: (1) a visual cue is essential for mate discrimination rather than odor or acoustic cues; (2) the visual cue is color and not shape, size, or motion; and (3) the color cue needs to be perceived as the relative balance of brightness at multiple wavelengths rather than the brightness at a specific wavelength. In addition, we introduced another skin-color mutation into the SLalpha-excess strain and found that this new strain and the original SLalpha-excess strain, which also overexpressed SLalpha but exhibited distinct skin colors, preferred different colors. This demonstrates that SLalpha is not a primary determinant of sexual preference. The symmetrically biased sexual preferences of the SLalpha deficient and SLalpha-excess strains may be acquired postnatally depending on their individual skin color or that of tank mates. PMID- 27260681 TI - Plasma/Serum Zinc Status During Aerobic Exercise Recovery: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Exercise and the subsequent recovery processes have been proposed to induce disturbances in zinc homeostasis. We previously reported acute increase in serum zinc concentration immediately after aerobic exercise; the change in the indices of zinc status during exercise recovery was not explored. OBJECTIVE: The aim of the current analysis is to determine the changes in zinc biomarkers during recovery from an aerobic exercise bout. METHODS: We conducted a systematic literature search on PubMed, Web of Science, Scopus and SPORTDiscus electronic databases from inception to 20 December 2014 to identify studies that investigated the acute effects of exercise on selected indices of zinc status. Meta-analyses were conducted to determine the change in serum zinc concentration during exercise recovery, defined as up to 4 h following exercise cessation, compared to pre-exercise levels. RESULTS: Forty-five studies were included in the systematic literature review, of which 12 studies (providing 18 comparisons) reported serum zinc levels after the cessation of exercise. During exercise recovery, serum zinc concentration was significantly lower than pre-exercise values (-1.31 +/- 0.22 MUmol/L, P < 0.001; mean +/- SE). Secondary analyses showed a significant decrease of serum zinc levels in all categories of participants' training status, mode of exercise and time of blood collection. Insufficient data were available for meta-analysis of other zinc biomarkers. CONCLUSIONS: The present analysis showed that serum zinc levels decrease significantly during exercise recovery, compared to pre-exercise levels. This extends our previous report of an increase in serum zinc immediately after exercise. We postulate that the exercise-induced fluctuations in zinc homeostasis are linked to the muscle repair mechanisms following exercise; the potential for zinc to enhance the exercise recovery process remains to be determined. PMID- 27260683 TI - Socioeconomic Correlates of Sedentary Behavior in Adolescents: Systematic Review and Meta-Analysis. AB - BACKGROUND: The body of evidence on associations between socioeconomic status (SES) and sedentary behaviors in adolescents is growing. OBJECTIVES: The overall aims of our study were to conduct a systematic review and meta-analysis of this evidence and to assess whether (1) the associations between SES and sedentary behavior are consistent in adolescents from low-middle-income and from high income countries, (2) the associations vary by domain of sedentary behavior, and (3) the associations vary by SES measure. METHODS: We performed a systematic literature search to identify population-based studies that investigated the association between SES and sedentary behavior in adolescents (aged 10-19 years). Only studies that presented risk estimates were included. We conducted meta analyses using random effects and univariate meta-regression and calculated pooled effect sizes (ES). RESULTS: Data from 39 studies were included; this provided 106 independent estimates for meta-analyses. Overall, there was an inverse association between SES and sedentary behavior (ES 0.89; 95 % confidence interval [CI] 0.81-0.98). However, the direction of the association varied: in high-income countries, SES was inversely associated with sedentary behavior (ES 0.67; 95 % CI 0.62-0.73), whereas in low-middle-income countries, there was a positive association between SES and sedentary behavior (ES 1.18; 95 % CI 1.04 1.34). In high-income countries, the associations were strongest for screen time (ES 0.68; 95 % CI 0.62-0.74) and television (TV) time (ES 0.58; 95 % CI 0.49 0.69), whereas in low-middle-income countries, the associations were strongest for 'other' screen time (i.e., computer, video, study time, but not including TV time) (ES 1.38; 95 % CI 1.07-1.79). All indicators of SES were negatively associated with sedentary behavior in high-income countries, but only resources (income and assets indexes) showed a significant positive association in low middle-income countries. CONCLUSION: The associations between SES and sedentary behavior are different in high- and low-middle-income countries, and vary by domain of sedentary behavior. These findings suggest that different approaches may be required when developing intervention strategies for reducing sedentary behavior in adolescents in different parts of the world. PMID- 27260682 TI - The Antioxidant Effect of Exercise: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Physical activity has been associated with reduced oxidative stress (OS) in observational studies and clinical trials. OBJECTIVE: The purpose of this systematic review and meta-analysis of controlled trials was to determine the effect of physical exercise on OS parameters. METHODS: We conducted a systematic review of the literature up to March 2016 that included the following databases: PubMed, SCOPUS, and Web of Science. A keyword combination referring to exercise training and OS was included as part of a more thorough search process. We also manually searched the reference lists of the articles. From an initial 1573 references, we included 30 controlled trials (1346 participants) in the qualitative analysis, 19 of which were included in the meta-analysis. All trials were conducted in humans and had at least one exercise intervention and a paired control group. Using a standardized protocol, two investigators independently abstracted data on study design, sample size, participant characteristics, intervention, follow-up duration, outcomes, and quantitative data for the meta analysis. Thus, the investigators independently assigned quality scores with a methodological quality assessment (MQA). RESULTS: The agreement level between the reviewers was 85.3 %. Discrepancies were solved in a consensus meeting. The MQA showed a total score in the quality index between 40 and 90 % and a mean quality of 55 %. Further, in a random-effects model, data from each trial were pooled and weighted by the inverse of the total variance. Physical training was associated with a significant reduction in pro-oxidant parameters (standard mean difference [SMD] -1.08; 95 % confidence interval [CI] -1.57 to -0.58; p < 0.001) and an increase in antioxidant capacity (SMD 1.45; 95 % CI 0.83-2.06; p < 0.001). CONCLUSION: The pooled analysis revealed that regardless of intensity, volume, type of exercise, and studied population, the antioxidant indicators tended to increase and pro-oxidant indicators tended to decrease after training. Therefore, we conclude that exercise training seems to induce an antioxidant effect. Thus, it is suggested that people practice some kind of exercise to balance the redox state, regardless of their health status, to improve health-related outcomes. PMID- 27260684 TI - Life With HIV: Insights from HIV-infected Women in Cameroon, Central Africa. AB - Women in Cameroon are disproportionately burdened by HIV illness. Understanding the impact HIV has on women is essential for developing interventions to enhance their quality of life. Our aim was to explore and provide an in-depth understanding of the daily experiences of a sample of women living with HIV in Cameroon. Qualitative semi-structured in-depth interviews were conducted with women (N = 30) from the northwest region of Cameroon who self-reported being infected with HIV. Participants shared that they had multiple challenges in their daily experiences living with HIV. The themes that emerged included: (a) receiving an HIV diagnosis is traumatic, (b) living with HIV is a constant struggle, (c) limited resources and support cause problems, and (d) stigma and powerlessness exacerbate the impact of HIV. We provide insight into the daily experiences of HIV-infected women in Cameroon. Implications for improving health care and social services to women living with HIV in Cameroon are suggested. PMID- 27260685 TI - Cholinergic enzymes and inflammatory markers in rats infected by Sporothrix schenckii. AB - The aim of this study was to evaluate the cholinesterase activity in serum, whole blood, and lymphocytes, as well as to verify its relation to immune response in rats experimentally infected by Sporothrix schenckii. For this study, 63 Wistar rats (Rattus norvegicus), male, adult were divided into three groups: the negative control group (GC: n = 21), the group infected subcutaneously (GSC: n = 21), and the group infected intraperitoneally (GIP: n = 21). The groups were divided into subgroups and the following variables were evaluated at 15, 30, and 40 days post-infection (PI): acetylcholinesterase (AChE) activity in lymphocytes and whole blood, butyrylcholinesterase (BChE) activity in serum, cytokines levels (IL-1, IL-6, TNFalpha, and INF-gamma), immunoglobulins levels (IgA, IgG, IgM, and IgE), and protein profile by electrophoresis. Both infected groups showed increased levels of inflammatory parameters (P < 0.05) in tissue and inflammatory infiltrates. The activities of AChE in lymphocytes and BChE in serum increased (P < 0.05) significantly in animals from the GSC group on day 40 PI compared to the GC group. Regarding the GIP, there was a marked increase in the AChE activity in lymphocytes on days 30 and 40 PI, and in whole blood on days 15, 30, and 40 PI compared to GC. Furthermore, IL-10, an anti-inflammatory cytokine, was also present in high levels during chronic systemic S. schenckii infections in animals. Therefore, it is concluded that cholinesterase has an important modulatory role in the immune response during granulomatous infection by S. schenckii. PMID- 27260687 TI - Preimplantation genetic screening-23 years to navigate and translate into the clinical arena. We need a new roadmap! PMID- 27260686 TI - Diagnostic and prognostic significance of serum apolipoprotein C-I in triple negative breast cancer based on mass spectrometry. AB - Women with triple-negative breast cancer (TNBC) have poor prognosis because of the aggressive nature of the tumor, delayed diagnosis and non-specific symptoms in the early stages. Identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes therefore remains an urgent clinical requirement.We obtained serum samples from a total of 380 recruited individuals split into mining and testing sets, with the aim of screening for reliable protein biomarkers from TNBC and non-TNBC (NTNBC) sera. Samples were assessed using mass spectrometry, followed by receiver operating characteristic (ROC), survival and hazard function curve as well as multivariate Cox regression analyses to ascertain the potential of the protein constituents as diagnostic and prognostic biomarkers for TNBC.We identified upregulated apolipoprotein C-I (apoC I) with a validated positive effect on TNBC tumorigenesis, with confirmation in an independent test set and minimization of systematic bias by pre-analytical parameters. The apoC-I protein had superior diagnostic ability in distinguishing between TNBC and NTNBC cases. Moreover, the protein presented a more robust potential prognostic factor for TNBC than NTNBC. The apoC-I protein identified in this study presents an effective novel diagnostic and prognostic biomarker for TNBC, indicating that measurement of the peak intensity at 7785 Da in serum samples could facilitate improved early detection and estimation of postoperative survival prognosis for TNBC. PMID- 27260688 TI - MiOXSYS: a novel method of measuring oxidation reduction potential in semen and seminal plasma. AB - OBJECTIVE: To measure oxidative reduction potential (ORP) in semen and seminal plasma and to establish their reference levels. DESIGN: ORP levels were measured in semen and seminal plasma. SETTING: Tertiary hospital. SUBJECT(S): Twenty-six controls and 33 infertile men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Static ORP (sORP) and capacitance ORP (cORP) were measured in semen and seminal plasma at time 0 and 120 minutes. Correlation of ORP was assessed between [1] semen and seminal plasma and [2] time 0 and 120 minutes. The association with sperm parameters was studied in (a) controls and (b) infertile patients, and a receiver operating characteristic curve was generated to establish the sORP cutoff. RESULT(S): Semen sORP and cORP levels were associated with seminal plasma levels at time 0 and time 120 minutes. In controls and infertile patients, an inverse relationship of sORP levels was established with concentration and total sperm count in semen as well as seminal plasma at time 0 and 120 minutes. Classification of subjects based on sperm motility showed that subjects with abnormal motility present with poor concentration, total count, morphology, and elevated levels of semen and seminal plasma sORP at time 120 minutes. The sORP cutoff of 1.48 in semen and 2.09 in seminal plasma based on motility was able to distinguish subjects with normal semen quality from those with abnormal semen quality. CONCLUSION(S): The MiOXSYS System can reliably measure ORP levels in semen and seminal plasma. ORP levels are not affected by semen age, making this new technology easy to employ in a clinical setting. PMID- 27260689 TI - Glenohumeral Hematoma Mimicking Persisting Anterior Shoulder Dislocation After Reduction. PMID- 27260690 TI - Diagnosis of Acquired Uterine Arteriovenous Malformation by Doppler Ultrasound. AB - BACKGROUND: Acquired uterine arteriovenous malformation (AVM) is a rare cause of postpartum vaginal bleeding and can often be confused with retained products of conception (RPOC). Certain findings on ultrasound (US) increase the likelihood for AVM, such as hypoechoic areas in the myometrium and high velocity, multidirectional blood flow. Recognizing these changes on bedside US can cue the physician to send the patient for further studying and lead to the correct diagnosis. CASE REPORT: A 31-year-old, multigravida, multiparous female presented 5 weeks post-cesarean section with heavy, intermittent vaginal bleeding. Patient had multiple previous visits for similar bleeding, including an evaluation for RPOC. Upon current presentation, the patient underwent an US in the emergency department with color and pulse wave Doppler. US revealed a hypoechoic area within the myometrium, with high velocity, bidirectional blood flow, raising the clinical suspicion for uterine AVM. Following confirmatory studies, the patient underwent successful embolization of the AVM. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The proper diagnosis of AVM is crucial, because the primary treatment modality for the alternative diagnosis of RPOC (i.e., dilation and curettage) can worsen vaginal bleeding and lead to shock or death, and is therefore contraindicated for uterine AVM. US is a quick bedside tool that can be used for rapid diagnosis of uterine AVM. PMID- 27260691 TI - Reply. PMID- 27260692 TI - Arizona's Emergency Medical Services for Children Pediatric Designation System for Emergency Departments. AB - BACKGROUND: In 2012, a voluntary certification program called Pediatric Prepared Emergency Care (PPEC) was established in Arizona as a system for pediatric emergency preparedness. Emergency medicine and pediatric specialists generated basic, intermediate, and advanced designation criteria. Dedicated medical management by a pediatric emergency specialist is required for advanced centers. Designation follows a site visit, review, and approval by the subcommittee and the Arizona Chapter of the American Academy of Pediatrics. DISCUSSION: Arizona has 5 designated pediatric emergency departments, all of which are in the southeast part of the state. Therefore, a designation system was implemented so that all emergency departments statewide can receive more training, support, and supervision of pediatric care. The goal was to create a self-sustaining network with active participation from member institutions while fostering the pediatric commitment. Since its inception, 39 hospitals and 5 tribal facilities have joined PPEC, equating to 51% of Arizona's emergency facilities. Of the hospitals, 7 are advanced, 6 are intermediate, and 17 are basic centers. In 2015, all of the 9 sites due for recertification were recertified. The multiple tiers allow for mutual accountability, sharing of resources, and improved quality of care for pediatrics in emergency departments statewide. CONCLUSION: PPEC enhances the quality of pediatric emergency preparedness by means of voluntary certification. The primary limitations are sustainability and funding, because an Emergency Medical Services for Children grant has offset the cost until now. The number of member facilities in this designation system is continually growing, and universal recertification shows sustainability. PMID- 27260693 TI - Fructose intake during gestation and lactation differentially affects the expression of hippocampal neurosteroidogenic enzymes in rat offspring. AB - Neurosteroids, steroidal hormones synthesized de novo from cholesterol within the brain, stimulate hippocampal functions such as neuron protection and synapse formation. Previously, we examined the effect of maternal fructose on the transcriptional regulation of neurosteroidogenic enzymes. We found that the mRNA expression level of the steroidogenic acute regulatory protein (StAR), peripheral benzodiazepine receptor (PBR), cytochrome P450(11beta), 11beta-hydroxysteroid dehydrogenase (HSD), and 17beta-HSD was altered. However, we could not determine whether maternal fructose intake played a role in the gestation or lactation period because the dam rats were fed fructose solution during both periods. Thus, in this study, we analyzed the hippocampi of the offspring of dams fed fructose during the gestation or lactation period. Maternal fructose consumption during either the gestation or lactation period did not affect the mRNA levels of StAR, P450(17alpha), 11beta-HSD-2, and 17beta-HSD-1. PBR expression was down-regulated, even when rats consumed fructose during the lactation period only, while fructose consumption during gestation tended to activate the expression of P450(11beta)-2. We found that maternal fructose intake during gestation and lactation differentially affected the expression of hippocampal neurosteroidogenic enzymes in the offspring. PMID- 27260694 TI - A Real-Time Monitoring System to Assess the Platelet Aggregatory Capacity of Components of a Tissue-Engineered Blood Vessel Wall. AB - Native blood vessels contain both an antiaggregatory intimal layer, which prevents platelet activation in the intact vessel, and a proaggregatory medial layer, which stimulates platelet aggregation upon vascular damage. Yet, current techniques for assessing the functional properties of tissue-engineered blood vessels may not be able to assess the relative effectiveness of both these pro- and antiaggregatory properties of the vessel construct. In this study, we present a novel technique for quantitatively assessing the pro- and antiaggregatory properties of different three-dimensional blood vessel constructs made using a layered fabrication method. This technique utilizes real-time measurements of cytosolic Ca(2+) signaling to assess platelet activation in fluorescently labeled human platelet suspensions using fluorescence spectrofluorimetry, while also permitting examination of thrombus formation upon the surface of the construct using fluorescent imaging of DiOC6-labeled platelets. Experiments using this method demonstrated that type I collagen hydrogels, commonly used as scaffolds for vascular tissue engineering, were unable to support significant platelet activation, while type I and III neo-collagen secreted from human coronary artery smooth muscle cells cultured within these hydrogels as the medial layer were able to support thrombus formation. The incorporation of an intimal layer consisting of human umbilical vein endothelial cells on top of the medial layer inhibited platelet activation and aggregation. These data demonstrate that the methodology presented here is able to quantitatively compare the capacity of different constructs to trigger or prevent platelet activation. As such, this technique may provide a useful tool for standardizing the assessment of the functional properties of tissue-engineered blood vessel constructs developed using different culturing techniques. PMID- 27260696 TI - Children's Right to Health: Implications for Decision-Making in Newborn Medical Care. PMID- 27260695 TI - Residential Moving and Preventable Hospitalizations. AB - OBJECTIVES: To investigate the association between moving home in the first year of life and subsequent emergency admissions for potentially preventable hospitalizations. METHODS: We undertook a cohort analysis of linked anonymized data on 237 842 children in the Welsh Electronic Cohort for Children. We included children born in Wales between April 1, 1999 and December 31, 2008. The exposure was the number of residential moves from birth up to 1 year. The main outcome was emergency admissions for potentially preventable hospitalizations (PPH) between the age of 1 and 5 years. RESULTS: After adjustment for confounders, we identified that moving home frequently in the first year of life was associated with an increased risk of emergency PPH between the ages of 1 and 5 when compared with not moving. We found significant differences associated with >=2 moves for the following: ear, nose, and throat infections (incidence risk ratio [IRR], 1.44; 95% confidence interval [CI], 1.29-1.61); convulsions/epilepsy (IRR, 1.58; 95% CI, 1.23-2.04); injuries (IRR, 1.33; 95% CI, 1.18-1.51); dehydration/gastroenteritis (IRR, 1.51; 95% CI, 1.21-1.88); asthma (IRR, 1.61; 95% CI, 1.19-2.16); influenza/pneumonia (IRR, 1.15; 95% CI, 1.00-1.32); and dental conditions (IRR, 1.30; 95% CI, 1.03-1.64) for >=1 moves. CONCLUSIONS: Children who move home in the first year of life are at substantially increased risk of emergency admissions for PPH in early childhood. Additional research that focuses on enhancing health and social support services for highly mobile families, educating parents about safety risks, and improving housing quality is warranted. PMID- 27260697 TI - Immunotherapy in Breast Cancer. AB - The importance of the tumor microenvironment including immune cell infiltrates in breast cancer has long been recognized. Tumor-infiltrating lymphocytes are prognostic and predictive; however, their prevalence as well as their prognostic and predictive power are subtype-dependent and appear most prominent in aggressive subtypes like triple-negative and HER2-positive disease. The immune responses observed in many cancers are attracted by tumor-associated antigens and, as suggested by recent research, by neoantigens - immunogenic antigens encoded for by non-synonymous mutations. The appealing promise of cancer vaccines has been pursued in breast cancer for over 2 decades; however, despite much effort having been put into vaccine trials, their clinical benefit, with the exception of some encouraging preliminary results, remains disappointing. The main hurdles compromising the efficacy of these vaccination strategies are the difficulties to generate broad and robust immune responses as well as to overcome immune escape mechanisms. The remarkable efficacy of immune checkpoint inhibitors in melanoma and lung cancer has set the ground for a race in the clinical development of numerous agents targeting these immune escape mechanisms in many tumor entities. Early clinical data in metastatic breast cancer suggests at least some clinical activity. This review discusses the current status and future perspectives of immunotherapy in breast cancer. PMID- 27260698 TI - Response to "A new approach to the management of ovarian endometrioma to prevent tissue damage and recurrence". PMID- 27260699 TI - Epilepsy in multiple sclerosis: The role of temporal lobe damage. AB - BACKGROUND: Although temporal lobe pathology may explain some of the symptoms of multiple sclerosis (MS), its role in the pathogenesis of seizures has not been clarified yet. OBJECTIVES: To investigate the role of temporal lobe damage in MS patients suffering from epilepsy, by the application of advanced multimodal 3T magnetic resonance imaging (MRI) analysis. METHODS: A total of 23 relapsing remitting MS patients who had epileptic seizures (RRMS/E) and 23 disease duration matched RRMS patients without any history of seizures were enrolled. Each patient underwent advanced 3T MRI protocol specifically conceived to evaluate grey matter (GM) damage. This includes grey matter lesions (GMLs) identification, evaluation of regional cortical thickness and indices derived from the Neurite Orientation Dispersion and Density Imaging model. RESULTS: Regional analysis revealed that in RRMS/E, the regions most affected by GMLs were the hippocampus (14.2%), the lateral temporal lobe (13.5%), the cingulate (10.0%) and the insula (8.4%). Cortical thinning and alteration of diffusion metrics were observed in several regions of temporal lobe, in insular cortex and in cingulate gyrus of RRMS/E compared to RRMS ( p< 0.05 for all comparisons). CONCLUSIONS: Compared to RRMS, RRMS/E showed more severe damage of temporal lobe, which exceeds what would be expected on the basis of the global GM damage observed. PMID- 27260747 TI - Simultaneous Endovascular Treatment of Tandem Internal Carotid Lesions: Case Report and Review of Literature. AB - The incidence of concomitant extracranial carotid artery stenosis and ipsilateral intracranial carotid aneurysm has been reported to vary between 2.8% and 5%. These complex lesions may present a challenge for treatment decision-making. This case report describes an asymptomatic male patient with severe carotid bifurcation stenosis, coupled with an unruptured supraclinoid internal carotid aneurysm. Both lesions were treated simultaneously. Patient underwent carotid stenting followed by aneurysm coiling in the same setting without any complication. PMID- 27260700 TI - Mutational and clinical analysis of the ENG gene in patients with pulmonary arterial hypertension. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare vascular disorder characterized by a capillary wedge pressure <= 15 mmHg and a mean pulmonary arterial pressure >= 25 mmHg at rest. PAH can be idiopathic, heritable or associated with other conditions. The aim of this study was to analyze the Endoglin (ENG) gene and assess the influence of the c.572G > A (p.G191D) mutation in patients with idiopathic or associated PAH. The correlation between the pathogenic mutations and clinical and functional parameters was further analyzed. RESULTS: Sixteen different changes in the ENG gene were found in 44 out of 57 patients. After in silico analysis, we classified eight mutations as pathogenic in 16 of patients. The c.572G>A (p.G191D) variation was observed in ten patients, and the analysis for the splicing process using hybrid minigenes, with pSPL3 vector to assess splicing alterations, do not generate a new transcript. Age at diagnosis (p = 0.049) and the 6-min walking test (p = 0.041) exhibited statistically significant differences between carriers and non-carriers of pathogenic mutations. Patients with pathogenic mutations exhibited disease symptoms 8 years before non-carriers. Five patients with pathogenic mutations were carriers of another mutation in the BMPR2 or ACVRL1 genes. CONCLUSIONS: We present a series of PAH patients with mutations in the ENG gene, some of them not previously described, exhibiting clinical and hemodynamic alterations suggesting that the presence of these mutations may be associated with the severity of the disease. Moreover, genetic analysis in patients with PAH may be of clinical relevance and indicates the complexity of the genetic background. PMID- 27260748 TI - Single-Session Endovascular Treatment of Symptomatic Lower Extremity Deep Vein Thrombosis: Is it Possible Even for Aged Thrombosis. AB - BACKGROUND: Feasibility of single-session mechanical thrombetomy, without thrombolytics, for the treatment of the subacute deep vein thrombosis (DVT) of the lower extremity remains poorly described. PURPOSE: To evaluate the feasibility and efficacy of single-session endovascular treatment of DVT of the lower extremity that is more than 10 days old. MATERIALS AND METHODS: From January 2010 to December 2013, single-session endovascular treatment was performed in 21 limbs of 21 patients (8 men and 13 women) with DVT more than 10 days old at our hospital. The mean age of the thrombosis was 21.5 days (range 11 45 days). Two patients had malignancy-related obstructions. A 14F introducer sheath was inserted through the popliteal vein followed by aspiration thrombectomy with a large bore catheter. Balloon angioplasty and/or maceration of the thrombus were added when needed. Stent insertions were performed for patients with combined iliac vein stenosis. Technical success, clinical success, mean procedure time, and complications were evaluated. RESULTS: The technical success rate was 90.5% (19 of 21 patients). Among the 19 successful cases, aspiration thrombectomy alone was performed in 16 (84.2%) patients, additional balloon angioplasty of the femoral vein was performed in 2 (10.5%) patients, and both balloon angioplasty of the femoral vein and rotational thrombectomy were performed in 1 (5.3%) patient. Iliac vein stenting was performed due to combined iliac vein narrowing in 13 (68.4%) of the 19 successful cases. The mean procedure time was 86 minutes (26-179 minutes). All of the patients with technical success (19 of 21 patients) showed marked improvement in symptoms at the time of discharge (clinical success). Unexplained gastrointestinal hemorrhage developed in 1 patient. CONCLUSION: Single-session endovascular treatment is feasible and effective even for patients with aged deep vein thrombosis of the lower extremity more than 10 days old. PMID- 27260749 TI - Late Leakage of the Aortic Stump After Removal of an Infected Graft: Successful Surgical Treatment. AB - The residual stump after excision of an infected aortic graft may be subject to acute blowout due to chronic mechanical stress on a weak arterial wall. We present a case of late aortic stump disruption that required revision after 12 months from graft removal. Our strategy consisted of avoiding reexposure of the pararenal aorta by creating a new supraceliac stump with healthy aortic wall after antegrade visceral debranching. This case confirms the need for long-term surveillance of aortic stumps. The use of a supraceliac approach minimizes the risk of intraoperative blowout and postoperative disruption. PMID- 27260750 TI - Compression Stockings for Prevention of Postthrombotic Syndrome: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The present meta-analysis aimed to evaluate the efficacy and safety of compression stockings for postthrombotic syndrome (PTS) prevention in patients with deep venous thrombosis (DVT). METHODS: Randomized controlled trials (RCTs) regarding the use of compression stockings for prevention of PTS were identified from the Medline, PubMed, and Embase databases as well as the Cochrane library. The resulting manuscripts were analyzed according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Six RCTs involving 1465 patients with DVT were included. The meta-analysis indicated no statistical differences between the compression stocking and the control groups in PTS incidence, using either the Villalta scale (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.23-1.74) or the Ginsberg scale (OR, 1.13; 95% CI, 0.72-1.77). Based on the Villalta scale categorization, there were no differences in the incidence of mild-moderate PTS (OR, 0.71; 95% CI, 0.36-1.41) or incidence of severe PTS (OR, 0.68; 95% CI, 0.15-3.11). The difference in the recurrence of venous thromboembolism (OR, 0.89; 95% CI, 0.61-1.30) was also not significant. In the 3 RCTs that reported side effects of compression stockings, they were primarily related to discomfort, including itching, erythema, and rash. CONCLUSION: The present meta-analysis has indicated that compression stockings may not prevent PTS, as determined by either the Villalta or the Ginsberg scale, in patients with DVT. However, owing to the limited number of trials, the evidence is not strong enough to draw a reliable conclusion. Further larger, randomized, double-blind, placebo-controlled, multicenter trials are needed. PMID- 27260751 TI - Long-Term Outcomes of Single-Port Laparoscopic Placement of Peritoneal Dialysis Catheter. AB - INTRODUCTION: Laparoscopic insertion of peritoneal dialysis (PD) catheter has become a preferred method compared to the traditional open technique for PD catheter insertion. We retrospectively report the outcome of 1-port laparoscopic placement PD catheters in our institution. METHODS: A total of 263 patients with end-stage renal disease who underwent single-trocar laparoscopic PD catheter insertion during a recent 6-year period were reviewed. Laparoscopic technique involves introducing a PD catheter over a stiff guidewire into the abdominal cavity through a 10-mm laparoscopic port. Pertinent clinical variables, procedural complications, and follow-up outcome were analyzed. RESULTS: There were 182 men and 81 women. The mean age was 56 years. Technical success was 95.8%. Catheter occlusion was the most common early complications (<6 months) that occurred in 4 (1.5%) patients. Late complications (> 6 months) including catheter occlusion, cuff extrusion, catheter leakage, catheter migration, infection, and hernia occurred in 5 patients (1.9%), 2 patients (0.8%), 3 patients (1.1%), 3 patients (1.1%), 6 patients (2.3%), and 4 patients (1.5), respectively. Mean follow-up time was 39 +/- 18 months. Catheter survival rate at 1, 2, 3, 4, and 5 years was 96%, 94%, 90%, 85%, and 82%, respectively. CONCLUSION: Laparoscopic PD catheter implantation via a single-trocar utilizing a stiff guidewire technique is feasible and safe. This method can result in low complication and high catheter survival rate. PMID- 27260752 TI - Dermoscopy of subacute cutaneous lupus erythematosus. PMID- 27260763 TI - Confirmatory factor analysis of 12-Item World Health Organization Disability Assessment Schedule in patients with musculoskeletal pain conditions. AB - OBJECTIVE: To investigate the factor structure of the 12 item World Health Organization Disability Assessment Schedule (WHODAS) 2.0. DESIGN: Cross-sectional cohort survey study. SETTING: Physical and Rehabilitation Medicine outpatient university clinic. SUBJECTS: The 408 consecutive patients with chronic musculoskeletal pain. MAIN MEASURES: Exploratory and confirmatory factor analysis. RESULTS: A two-factor model most accurately fit the observed data of musculoskeletal pain patients (root mean square error of approximation 0.049, relative Chi square value 1.99). Twelve WHODAS 2.0 items were distributed between two factors with covariance between them of 0.8. The first factor contained domains related mostly to physical functioning, while another was associated mostly with social and cognitive functioning. There were a few differences between single items in their importance in defining the variance within these two factors. Of the six International Classification of Functioning, Disability and Health domains belonging to the first construct, the ability to carry out household responsibilities explained most, 84% of the total variance in this construct. For the second factor, the ability to participate in community activities seemed to be the most important, explaining 85% of the total variance in this construct. CONCLUSIONS: In this study, the two-factor structure model of the 12-item WODAS 2.0 demonstrated the most accurate fit within patients with musculoskeletal pain conditions. PMID- 27260753 TI - Spliceosomal component Sf3b1 is essential for hematopoietic differentiation in zebrafish. AB - SF3B1 (Splicing factor 3b, subunit 1) is one of the most commonly mutated factors in myelodysplastic syndrome (MDS). Although the genetic correlation between SF3B1 mutations and MDS etiology are quite strong, no in vivo model currently exists to explore how SF3B1 loss alters blood cell development. Using zebrafish mutants, we show here that proper function of Sf3b1 is required for all hematopoietic lineages. As in MDS patients, zebrafish sf3b1 mutants develop a macrocytic-anemia like phenotype due to a block in maturation at a late progenitor stage. The mutant embryos also develop neutropenia, because their primitive myeloid cells fail to mature and turn on differentiation markers such as l-plastin and myeloperoxidase. In contrast, production of definitive hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelial cells within the dorsal aorta is greatly diminished, whereas arterial endothelial cells are correctly fated. Notch signaling, imperative for the endothelial-to-hematopoietic transition, is also normal, indicating that HSPC induction is blocked in sf3b1 mutants downstream or independent of Notch signaling. The data demonstrate that Sf3b1 function is necessary during key differentiation fate decisions in multiple blood cell types. Zebrafish sf3b1 mutants offer a novel animal model with which to explore the role of splicing in hematopoietic development and provide an excellent in vivo system with which to delve into the question of why and how Sf3b1 dysfunction is detrimental to hematopoietic differentiation, which could improve MDS diagnosis and treatment. PMID- 27260764 TI - Results of a Pilates exercise program in patients with chronic non-specific low back pain: a randomized controlled trial. AB - OBJECTIVE: To investigate the effects of a Pilates exercise program on disability, pain, lumbar mobility, flexibility and balance in patients with chronic non-specific low back pain. DESIGN: Randomized controlled trial. SETTING: University laboratory. PARTICIPANTS: A total of 54 patients with chronic non specific low back pain. INTERVENTION: Patients were randomly allocated to an experimental group ( n=27) included in a Pilates exercise program or to a control group ( n=27) receiving information in a form of a leaflet. MAIN OUTCOME MEASURES: Disability (Roland-Morris Disability Questionnaire and Oswestry Disability Index), current, average and pain at it least and at its worst (Visual Analogue Scales), lumbar mobility (modified Shober test), flexibility (finger-to floor test) and balance (single limb stance test) were measured at baseline and after the intervention. RESULTS: A between-group analysis showed significant differences in the intervention group compared to the control group for both disability scores, the Rolland-Morris questionnaire (mean change+/-standard deviation of 5.31+/-3.37 and 2.40+/-6.78 respectively and between-groups mean difference of 3.2 +/- 4.12, p=0.003) and the Oswestry Disability Index ( p<0.001), current pain ( p=0.002) and pain at it least ( p=0.033), flexibility (0.032) and balance (0.043). CONCLUSIONS: An 8-week Pilates exercise program is effective in improving disability, pain, flexibility and balance in patients with chronic non-specific low back pain. PMID- 27260765 TI - Reverse shoulder arthroplasty after failed pectoralis major tendon transfer with a minimum follow-up of 5 years. A case series. AB - BACKGROUND: Treatment strategies after failed pectoralis major tendon transfer (PMTT) are scarce in literature and no information is available for patients treated with reverse shoulder arthroplasty (RSA) for failed PMTT. METHODS: We performed a retrospective outcome study of all patients who underwent revision with RSA after failed PMTT at our institution. From 1999 to 2009 we included 8 patients (8 shoulders). The minimum follow-up was 5 years with a mean follow-up time of 97 months (range, 64-134). Clinical and radiological evaluation comprised range of motion, Constant Murley score (CMS), Simple Shoulder Test (SST) as well as standard X-rays in 2 planes. Pain was measured using VAS pain scale. The patients were asked to rate their satisfaction at final follow-up. RESULTS: All outcome measures improved significantly post-surgical compared to pre-surgical, including the CMS (17.8-62.8), SST (1.8-7.3) and VAS (7.1-1). Active abduction and anterior flexion improved significantly (p < .001) from 65.6 degrees to 125 degrees and from 62.5 degrees to 136.3 degrees , respectively. There were 2 complications. One patient sustained transient musculocutaneous nerve palsy that resolved completely after 5 months and one patient sustained postoperative hematoma and had to be revised 4 days after surgery. 4 (50%) patients rated their results as excellent and 4 (50%) rated them as good. CONCLUSIONS: RSA is a good option for treating patients after failed pectoralis major tendon transfer. After a minimum follow-up of 5 years, functional outcome is good and patient satisfaction is high. LEVEL OF EVIDENCE: Level IV, Case series, Treatment study. PMID- 27260766 TI - Occupational asthma. PMID- 27260767 TI - The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease. AB - The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID- 27260769 TI - Statins for primary prevention in practice: clinical use in Wales and the NICE guideline effect. PMID- 27260768 TI - What Happens in the Thymus Does Not Stay in the Thymus: How T Cells Recycle the CD4+-CD8+ Lineage Commitment Transcriptional Circuitry To Control Their Function. AB - MHC-restricted CD4(+) and CD8(+) T cells are at the core of most adaptive immune responses. Although these cells carry distinct functions, they arise from a common precursor during thymic differentiation, in a developmental sequence that matches CD4 and CD8 expression and functional potential with MHC restriction. Although the transcriptional control of CD4(+)-CD8(+) lineage choice in the thymus is now better understood, less was known about what maintains the CD4(+) and CD8(+) lineage integrity of mature T cells. In this review, we discuss the mechanisms that establish in the thymus, and maintain in postthymic cells, the separation of these lineages. We focus on recent studies that address the mechanisms of epigenetic control of Cd4 expression and emphasize how maintaining a transcriptional circuitry nucleated around Thpok and Runx proteins, the key architects of CD4(+)-CD8(+) lineage commitment in the thymus, is critical for CD4(+) T cell helper functions. PMID- 27260770 TI - High-risk behaviors while driving: A population-based study from Iran. AB - OBJECTIVE: Traffic injuries are becoming one of the most important challenges of public health systems. Because these injuries are mostly preventable, the aim of this study is to evaluate the four main high-risk behaviors while driving. METHODS: This cross-sectional study was conducted on a random sample from the population of Mashhad, Iran, in 2014. A checklist and a previously validated questionnaire for the transtheoretical stages of change model (TTM) were used for data collection. Statistical analyses were performed using SPSS 11.5 software with P <.05 statistically significant. RESULTS: Totally 431 individuals were included with a mean age of 30 +/- 11.3 years. Forty-three percent (183) were male. The TTM model revealed that participants were mostly in pre-actional phases regarding not using a cell phone while driving (80%), fastening the driver's seat belt (66%), front seat belt (68%), and rear seat belt (85%) The penalty was a protective factor only for using cellphone (odd ratio [OR] = 0.82, 95% confidence interval [CI], 0.68-0.98). Lower education (OR = 0.12, 95% CI, 0.01-0.94) and male gender (OR = 0.35, 95% CI, 0.14-0.83) were indicative of lower rates of fastening the front and rear seat belts. CONCLUSION: The stages of change model among study participants is a proper reflection of the effectiveness of the current policies. More serious actions regarding these high-risk behaviors should be considered in legislation. PMID- 27260772 TI - Advances in Cancer Therapy: Immunotherapies. PMID- 27260771 TI - Pharmacological Modulation of Proton Channel Hv1 in Cancer Therapy: Future Perspectives. AB - The pharmacological modulation of the immunosuppressive tumor microenvironment has emerged as a relevant component for cancer therapy. Several approaches aiming to deplete innate and adaptive suppressive populations, to circumvent the impairment in antigen presentation, and to ultimately increase the frequency of activated tumor-specific T cells are currently being explored. In this review, we address the potentiality of targeting the voltage-gated proton channel, Hv1, as a novel strategy to modulate the tumor microenvironment. The function of Hv1 in immune cells such as macrophages, neutrophils, dendritic cells, and T cells has been associated with the maintenance of NADPH oxidase activity and the generation of reactive oxygen species, which are required for the host defense against pathogens. We discuss evidence suggesting that the Hv1 proton channel could also be important for the function of these cells within the tumor microenvironment. Furthermore, as summarized here, tumor cells express Hv1 as a primary mechanism to extrude the increased amount of protons generated metabolically, thus maintaining physiologic values for the intracellular pH. Therefore, because this channel might be relevant for both tumor cells and immune cells supporting tumor growth, the pharmacological inhibition of Hv1 could be an innovative approach for cancer therapy. With that focus, we analyzed the available compounds that inhibit Hv1, highlighted the need to develop better drugs suitable for patients, and commented on the future perspectives of targeting Hv1 in the context of cancer therapy. PMID- 27260773 TI - [(11)C]UCB-A, a novel PET tracer for synaptic vesicle protein 2A. AB - INTRODUCTION: Development of a selective and specific high affinity PET tracer, [(11)C]UCB-A, for the in vivo study of SV2A expression in humans. Radiochemistry and preclinical studies in rats and pigs including development of a tracer kinetic model to determine VT. A method for the measurement of percent intact tracer in plasma was developed and the radiation dosimetry was determined in rats. RESULTS: 3-5GBq of [(11)C]UCB-A could be produced with radiochemical purity exceeding 98% with a specific radioactivity of around 65GBq/MUmol. In vitro binding showed high selective binding towards SV2A. [(11)C]UCB-A displayed a dose dependent and reversible binding to SV2A as measured with PET in rats and pigs and the VT could be determined by Logan analysis. The dosimetry was favorable and low enough to allow multiple administrations of [(11)C]UCB-A to healthy volunteers, and the metabolite analysis showed no sign of labeled metabolites in brain. CONCLUSIONS: We have developed the novel PET tracer, [(11)C]UCB-A, that can be used to measure SV2A expression in vivo. The dosimetry allows up to 5 administrations of 400MBq of [(11)C]UCB-A in humans. Apart from measuring drug occupancy, as we have shown, the tracer can potentially be used to compare SV2A expression between individuals because of the rather narrow range of baseline VT values. This will have to be further validated in human studies. PMID- 27260774 TI - Radiotherapeutic bandage for the treatment of squamous cell carcinoma of the skin. AB - INTRODUCTION: Squamous cell carcinoma (SCC) is the second most common form of skin cancer in the United States. The efficacy of a pharmaceutically elegant radiotherapeutic bandage, previously described by us for application against SCC of the skin, was tested for the first time in vivo using a subcutaneous SCC mouse model and a therapeutically relevant radiation dose. METHODS: Female athymic nude mice were injected with human Colo-16 SCC cells subcutaneously and after eight days (average tumor volume: 35+/-8.6mm(3)) received no treatment, or were exposed to non-radioactive or radioactive (92.5+/-18.5MBq) bandages for approximately 1h (n=10 per group). After treatment, tumors were measured over fifteen days, tumor volume ratios (TVRs) compared and histopathology performed. RESULTS: Fifteen days after treatment, the TVR of the radioactive bandage treatment group was 3.3+/ 4.5, while TVRs of the non-radioactive bandage treatment and no treatment control groups were 33.2+/-14.7 and 26.9+/-12.6, respectively. At the time of necropsy, there was mild focal epidermal hyperplasia surrounding a small area of epidermal ulceration in the radioactive bandage group. No other examined tissue (i.e., muscle, liver, kidney, lung, spleen and heart) showed significant lesions. CONCLUSIONS: Our radiotherapeutic bandage exhibits promising efficacy against SCC of the skin in a mouse model. It can be individually tailored for easy application on tumor lesions of all shapes and sizes, and could complement or possibly replace surgery in the clinic. PMID- 27260775 TI - (99m)Tc-labeled gastrins of varying peptide chain length: Distinct impact of NEP/ACE-inhibition on stability and tumor uptake in mice. AB - INTRODUCTION: In situ inhibition of neutral endopeptidase (NEP) has been recently shown to impressively increase the bioavailability and tumor uptake of biodegradable gastrin radioligands. Furthermore, angiotensin converting enzyme (ACE) has been previously shown to cleave gastrin analogs in vitro. In the present study, we have assessed the effects induced by single or dual NEP/ACE inhibition on the pharmacokinetic profile of three (99m)Tc-labeled gastrins of varying peptide chain length: [(99m)Tc]SG6 ([(99m)Tc-N4-Gln(1)]gastrin(1-17)), [(99m)Tc]DG2 ([(99m)Tc-N4-Gly(4),DGlu(5)]gastrin(4-17)) and [(99m)Tc]DG4 ([(99m)Tc-N4-DGlu(10)]gastrin(10-17)). METHODS: Mouse blood samples were collected 5min after injection of each of [(99m)Tc]SG6/DG2/DG4 together with: a) vehicle, b) the NEP-inhibitor phosphoramidon (PA), c) the ACE-inhibitor lisinopril (Lis), or d) PA plus Lis and were analyzed by RP-HPLC for radiometabolite detection. Biodistribution was studied in SCID mice bearing A431 CCK2R(+/-) xenografts at 4h postinjection (pi). [(99m)Tc]SG6 or [(99m)Tc]DG4 was coinjected with either vehicle or the above described NEP/ACE-inhibitor regimens; for [(99m)Tc]DG2 control and PA animal groups were only included. RESULTS: Treatment of mice with PA induced significant stabilization of (99m)Tc radiotracers in peripheral blood, while treatment with Lis or Lis+PA affected the stability of des(Glu)5 [(99m)Tc]DG4 only. In line with these findings, PA coinjection led to notable amplification of tumor uptake of radiopeptides compared to controls (P<0.01). Only [(99m)Tc]DG4 profited by single Lis (2.06+/ 0.39%ID/g vs 0.99+/-0.13%ID/g in controls) or combined Lis+PA coinjection (8.91+/ 1.61%ID/g vs 4.89+/-1.33%ID/g in PA-group). Furthermore, kidney uptake remained favourably low and unaffected by PA and/or Lis coinjection only in the case of [(99m)Tc]DG4 (<1.9%ID/g) resulting in the most optimal tumor-to-kidney ratios. CONCLUSIONS: In situ NEP/ACE-inhibition diversely affected the in vivo profile of (99m)Tc-radioligands based on different-length gastrins. Truncated [(99m)Tc]DG4 exhibited overall the most attractive profile during combined NEP/ACE-inhibition in mouse models, providing new opportunities for CCK2R-expressing tumor imaging in man with SPECT. PMID- 27260776 TI - Increased choline uptake in macrophages and prostate cancer cells does not allow for differentiation between benign and malignant prostate pathologies. AB - INTRODUCTION: Inflammatory cells may contribute to the choline uptake in different prostate pathologies. The aim of this study was (i) to assess if inflammatory cells incorporate choline and (ii) to potentially detect differences compared to FDG uptake. Therefore we investigated the uptake of [(3)H]choline and [(18)F]FDG in human prostate carcinoma cells and human inflammatory cells. METHODS: Macrophages were cultured from isolated mononuclear cells, gained by density gradient centrifugation of human buffy coats. T-lymphocytes, B lymphocytes and granulocytes were enriched by density gradient centrifugation before cell sorting by means of flow cytometry was performed. [(3)H]choline and [(18)F]FDG uptake of isolated inflammatory cells as well as of LNCaP and PC-3 human prostate carcinoma cells was assessed simultaneously in dual tracer uptake experiments. RESULTS: Macrophages showed highest [(3)H]choline and [(18)F]FDG uptake compared to the tracer uptake rates of leukocytes. [(3)H]choline uptake of macrophages was in the same range as in prostate cancer cells. Lipopolysaccharide stimulation of macrophages resulted in an increase of [(18)F]FDG uptake in macrophages, but not in an increased [(3)H]choline uptake. CONCLUSIONS: The high [(3)H]choline uptake in macrophages may be a source of false-positive PET results in diagnosis of prostate cancer by choline-PET/CT. As already known from FDG-PET, discrimination between tumor and inflammation in prostate cancer patients is not possible via choline-PET. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: The application of choline-PET for reliable primary prostate cancer detection and delineation has to be queried. PMID- 27260777 TI - New (68)Ga-PhenA bisphosphonates as potential bone imaging agents. AB - INTRODUCTION: In vivo positron emission tomography (PET) imaging of the bone using [(68)Ga]bisphosphonates may be a valuable tool for cancer diagnosis and monitoring therapeutic treatment. We have developed new [(68)Ga]bisphosphonates based on the chelating group, AAZTA (6-[bis(hydroxycarbonyl-methyl)amino]-1,4 bis(hydroxycarbonyl methyl)-6-methylperhydro-1,4-diazepine). METHOD: Phenoxy derivative of AAZTA (2,2'-(6-(bis(carboxymethyl)amino)-6-((4-(2 carboxyethyl)phenoxy)methyl)-1,4-diazepane-1,4-diyl)diacetic acid), PhenA, 2, containing a bisphosphonate group (PhenA-BPAMD, 3, and PhenA-HBP, 4) was prepared. Labeling of these chelating agents with (68)Ga was evaluated. RESULTS: The ligands reacted rapidly in a sodium acetate buffer with [(68)Ga]GaCl3 eluted from a commercially available (68)Ge/(68)Ga generator (pH4, >95% labeling at room temperature in 5min) to form [(68)Ga]PhenA-BPAMD, 3, and [(68)Ga]PhenA-HBP, 4. The improved labeling condition negates the need for further purification. The (68)Ga bisphosphonate biodistribution and autoradiography of bone sections in normal mice after an iv injection showed excellent bone uptake. CONCLUSION: New (68)Ga labeled bisphosphonates may be useful as in vivo bone imaging agents in conjunction with positron emission tomography (PET). PMID- 27260778 TI - Noninvasive evaluation of nicotinic acetylcholine receptor availability in mouse brain using single-photon emission computed tomography with [(123)I]5IA. AB - INTRODUCTION: Nicotinic acetylcholine receptors (nAChRs) are of great interest because they are implicated in higher brain functions. Nuclear medical imaging is one of the useful techniques for noninvasive evaluation of physiological and pathological function in living subjects. Recent progress in nuclear medical imaging modalities enables the clear visualization of the organs of small rodents. Thus, translational research using nuclear medical imaging in transgenic mice has become possible and helps to elucidate human disease pathology. However, imaging of alpha4beta2 nAChRs in the mouse brain has not yet been performed. The purpose of this study was to assess the feasibility of single-photon emission computed tomography (SPECT) with 5-[(123)I]iodo-3-[2(S) azetidinylmethoxy]pyridine ([(123)I]5IA) for evaluating alpha4beta2 nAChR availability in the mouse brain. METHODS: A 60-min dynamic SPECT imaging session of alpha4beta2 nAChRs in the mouse brain was performed. The regional distribution of radioactivity in the SPECT images was compared to the density of alpha4beta2 nAChRs measured in an identical mouse. Alteration of nAChR density in the brains of Tg2576 mice was also evaluated. RESULTS: The mouse brain was clearly visualized by [(123)I]5IA-SPECT and probe accumulation was significantly inhibited by pretreatment with (-)-nicotine. The regional distribution of radioactivity in SPECT images showed a significant positive correlation with alpha4beta2 nAChR density measured in an identical mouse brain. Moreover, [(123)I]5IA-SPECT was able to detect the up-regulation of alpha4beta2 nAChRs in the brains of Tg2576 transgenic mice. CONCLUSIONS: [(123)I]5IA-SPECT imaging would be a promising tool for evaluating alpha4beta2 nAChR availability in the mouse brain and may be useful in translational research focused on nAChR-related diseases. PMID- 27260779 TI - Fully automated radiosynthesis of N(1)-[(18)F]fluoroethyl-tryptophan and study of its biological activity as a new potential substrate for indoleamine 2,3 dioxygenase PET imaging. AB - INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial step in the catabolism of l-tryptophan along the kynurenine pathway and exerts immunosuppressive properties in inflammatory and tumor tissues by blocking locally T-lymphocyte proliferation. Recently, 1-(2-[(19)F]fluoroethyl)-dl tryptophan (1-[(19)F]FE-dl-Trp) was reported as a good and specific substrate of this enzyme. Herein, the radiosynthesis of its radioactive isotopomer (1 [(18)F]FE-dl-Trp, dl-[(18)F]5) is presented along with in vitro enzymatic and cellular uptake studies. METHODS: The one-pot n.c.a. radiosynthesis of this novel potential PET imaging tracer, including HPLC purification and formulation, has been fully automated on a FASTlabTM synthesizer. Chiral separation of both isomers and their formulation were implemented on a second cassette. In vitro enzymatic and cellular uptake studies were then conducted with the d-, l- and dl radiotracers. RESULTS: The radiolabeling of the tosylate precursor was performed in DMF (in 5min; RCY: 57% (d.c.), n=3). After hydrolysis, HPLC purification and formulation, dl-[(18)F]5 was obtained with a global radiochemical yield of 18+/ 3% (not decay corrected, n=7, in 80min) and a specific activity of 600+/ 180GBq/MUmol (n=5). The subsequent separation of l- and d-enantiomers was performed by chiral HPLC and both were obtained after formulation with an RCY (d.c.) of 6.1% and 5.8%, respectively. In vitro enzymatic assays reveal that l [(18)F]5 is a better substrate than d-[(18)F]5 for human IDO. In vitro cellular assays show an IDO-specific uptake of the racemate varying from 30% to 50% of that of l-[(18)F]5, and a negligible uptake of d-[(18)F]5. CONCLUSION: In vitro studies show that l-[(18)F]5 is a good and specific substrate of hIDO, while presenting a very low efflux. These results confirm that l-[(18)F]5 could be a very useful PET radiotracer for IDO expressing cells in cancer imaging. PMID- 27260780 TI - Thermostabilization of indigenous multiplex polymerase chain reaction reagents for detection of enterotoxigenic Staphylococcus aureus. AB - BACKGROUND/PURPOSE: Among DNA-based techniques, polymerase chain reaction (PCR) is the most widely accepted molecular tool for the detection of pathogens. However, the technique involves several reagents and multiple pipetting steps that often lead to error-prone results. Additionally, the reagents entail a cold chain facility to maintain their stability during storage and transportation. The main aim of the present study was to simplify the utility of a pre-optimized multiplex PCR format that was developed to detect toxigenic strains of Staphylococcus aureus by providing stable, pre-mixed, and ready-to-use master mix in a lyophilized formulation. METHODS: Master mix containing all reagents except the template was lyophilized in the presence of an excipient lyoprotectant to achieve long-term stability without altering the sensitivity, specificity and PCR performance. Bromophenol blue was also included in the master mix to reduce the risk of external contamination during gel loading. The stability of lyophilized master mix was analyzed at different temperatures. The PCR performance was also examined after exposure of master mix to notable temperature fluctuations during transportation. RESULTS: The shelf-life of lyophilized master mix was estimated to be 1.5 months at ambient temperature and 6 months at 4 degrees C. Stability was unaffected by temperature fluctuations during transportation even in cold chain-free conditions, thus reducing the cost required for cold storage. CONCLUSION: The sensitive, cost-effective, ready-to-use, and ambient temperature stable formulation could be implemented as a detection tool in food analysis and diagnostic laboratories and hospitals and for on-field application outside the laboratories, as well as for detection of toxigenic strains of S. aureus. PMID- 27260781 TI - In vitro and in vivo antibacterial activity of tigecycline against Vibrio vulnificus. AB - BACKGROUND/PURPOSE: The aim of this study is to investigate the role of tigecycline in Vibrio vulnificus infection. METHODS: Eight randomly selected clinical V. vulnificus isolates were studied to obtain the minimal inhibitory concentrations (MICs) of minocycline, cefotaxime, and tigecycline, and the time kill curves of tigecycline alone or in combination with other drugs. A peritonitis mouse model was used for the evaluation of the therapeutic efficacy of tigecycline alone or cefotaxime in combination with minocycline or tigecycline. RESULTS: The MIC of minocycline, cefotaxime, and tigecycline for eight clinical V. vulnificus isolates was 0.06-0.12 MUg/mL, 0.03-0.06 MUg/mL, and 0.03-0.06 MUg/mL, respectively. In time-killing studies, at the concentration of 1 * MIC, the inhibitory effect of tigecycline persisted for 24 hours in five of eight isolates. With 2 * MIC and trough level, the inhibitory effect was noted in all isolates for 24 hours. With the combination of minocycline plus cefotaxime and tigecycline plus cefotaxime at 1/2 * MIC, the bactericidal effect was noted in 25% and 62.5% of eight isolates and synergism in 50% and 75% of isolates. With a low (1.25 * 105 CFU/mL) inoculum, all infected mice survived with tigecycline alone, tigecycline plus cefotaxime, or minocycline plus cefotaxime on the 14th day. At the inoculum of 1.25 * 106 CFU, the survival rate was 33.3% on the 14th day in the tigecycline plus cefotaxime-treated group, but none of the mice treated by tigecycline alone or minocycline plus cefotaxime survived (33.3% vs. 0%, p = 0.01 by Fisher's exact test). CONCLUSION: Our in vitro combination and animal studies indicate that tigecycline could be an option for the treatment of invasive V. vulnificus infections. PMID- 27260782 TI - Modeling methodology for the accurate and prompt prediction of symptomatic events in chronic diseases. AB - Prediction of symptomatic crises in chronic diseases allows to take decisions before the symptoms occur, such as the intake of drugs to avoid the symptoms or the activation of medical alarms. The prediction horizon is in this case an important parameter in order to fulfill the pharmacokinetics of medications, or the time response of medical services. This paper presents a study about the prediction limits of a chronic disease with symptomatic crises: the migraine. For that purpose, this work develops a methodology to build predictive migraine models and to improve these predictions beyond the limits of the initial models. The maximum prediction horizon is analyzed, and its dependency on the selected features is studied. A strategy for model selection is proposed to tackle the trade off between conservative but robust predictive models, with respect to less accurate predictions with higher horizons. The obtained results show a prediction horizon close to 40min, which is in the time range of the drug pharmacokinetics. Experiments have been performed in a realistic scenario where input data have been acquired in an ambulatory clinical study by the deployment of a non intrusive Wireless Body Sensor Network. Our results provide an effective methodology for the selection of the future horizon in the development of prediction algorithms for diseases experiencing symptomatic crises. PMID- 27260783 TI - Information bottleneck based incremental fuzzy clustering for large biomedical data. AB - Incremental fuzzy clustering combines advantages of fuzzy clustering and incremental clustering, and therefore is important in classifying large biomedical literature. Conventional algorithms, suffering from data sparsity and high-dimensionality, often fail to produce reasonable results and may even assign all the objects to a single cluster. In this paper, we propose two incremental algorithms based on information bottleneck, Single-Pass fuzzy c-means (spFCM-IB) and Online fuzzy c-means (oFCM-IB). These two algorithms modify conventional algorithms by considering different weights for each centroid and object and scoring mutual information loss to measure the distance between centroids and objects. spFCM-IB and oFCM-IB are used to group a collection of biomedical text abstracts from Medline database. Experimental results show that clustering performances of our approaches are better than such prominent counterparts as spFCM, spHFCM, oFCM and oHFCM, in terms of accuracy. PMID- 27260784 TI - Comprehensive oral-health assessment of individuals with acquired brain-injury in neuro-rehabilitation setting. AB - PRIMARY OBJECTIVE: To perform a detailed clinical oral health assessment and oral health-related social and behavioural aspect assessment in individuals with acquired brain injury (ABI). RESEARCH DESIGN: Prospective observational study. METHODS AND PROCEDURES: Thirteen individuals with ABI were recruited. Individual's social and behavioural history, bed-side oral examination score (BOE), tooth condition and periodontal status (bleeding, plaque and clinical attachment loss) were thoroughly examined. The entire examination took up to 60 minutes, using proper dental armamentarium. MAIN OUTCOMES AND RESULTS: All evaluated individuals were diagnosed with chronic generalized periodontitis. A relationship between active periodontal disease and severe BOE score was observed (p = 0.01). Significant interaction between severe BOE scores (>= 15 or >= 14) and periodontal disease severity of >= 2 mm (p = 0.01) was observed. The same interaction was seen between severe BOE scores and the combination of 75% extent and 2 mm severity (p = 0.01). Severity and activity of periodontitis showed dependence on individual brushing frequency (p = 0.03 and p = 0.05, respectively). CONCLUSIONS: Individuals with ABI had a poor status across a range of oral-, dental- and periodontal-related parameters. Further structured studies are required to define evidence-based assessment approaches for such clinical reality. PMID- 27260785 TI - Innovative use of recovered municipal solid waste incineration bottom ash as a component in growing media. AB - The utilisation of municipal solid waste incineration bottom ash has been extensively studied, for example, in the unbound layers of roads and the products of cement and concrete industry. On the other hand, less attention has been given to other innovative utilisation possibilities, such as using the municipal solid waste incineration bottom ash as a component in growing media of plants. The municipal solid waste incineration bottom ash contains useful substances, such as calcium, that can influence plant growth in a positive manner. Therefore, the utilisation of this waste-derived material in the growing media may substitute the use of commercial fertilisers. Since the municipal solid waste incineration bottom ash also contains hazardous substances that can be toxic to plants, the main aim of this study was to add different amounts of recovered municipal solid waste incineration bottom ash in the growing media and to evaluate the effect of this material on plant growth. Based on the obtained results, the concentration of, for example copper and zinc, increased in test plants; ryegrass and barley, when recovered municipal solid waste incineration bottom ash was added in their growing media. On the other hand, this did not have a significant effect on plant growth, if compared with the growth of plants in commercially produced growing medium. Furthermore, the replacement of natural sand with municipal solid waste incineration bottom ash had a positive liming effect in the growing media. Overall, these findings suggest that the utilisation of recovered municipal solid waste incineration bottom ash as a component in growing media is possible and, thus, may allow more widespread and innovative use of this waste-derived material. PMID- 27260786 TI - Proportion of Pelvic Inflammatory Disease Cases Caused by Chlamydia trachomatis: Consistent Picture From Different Methods. AB - BACKGROUND: Pelvic inflammatory disease (PID) is a leading cause of both tubal factor infertility and ectopic pregnancy. Chlamydia trachomatis is an important risk factor for PID, but the proportion of PID cases caused by C. trachomatis is unclear. Estimates of this are required to evaluate control measures. METHODS: We consider 5 separate methods of estimating age-group-specific population excess fractions (PEFs) of PID due to C. trachomatis, using routine data, surveys, case control studies, and randomized controlled trials, and apply these to data from the United Kingdom before introduction of the National Chlamydia Screening Programme. RESULTS: As they are informed by randomized comparisons and national exposure and outcome estimates, our preferred estimates of the proportion of PID cases caused by C. trachomatis are 35% (95% credible interval [CrI], 11%-69%) in women aged 16-24 years and 20% (95% CrI, 6%-38%) in women aged 16-44 years in the United Kingdom. There is a fair degree of consistency between adjusted estimates of PEF, but all have wide 95% CrIs. The PEF decreases from 53.5% (95% CrI, 15.6% 100%) in women aged 16-19 years to 11.5% (95% CrI, 3.0%-25.7%) in women aged 35 44 years. CONCLUSIONS: The PEFs of PID due to C. trachomatis decline steeply with age by a factor of around 5-fold between younger and older women. Further studies of the etiology of PID in different age groups are required. PMID- 27260787 TI - [Chronic fatigue syndrome: A new disorder?] AB - More than 30 years after its individualization, chronic fatigue syndrome (CFS) remains a debilitating condition for the patient and a confusing one to the physicians, both because of diagnostic difficulties and poorly codified management. Despite the numerous work carried out, its pathophysiology remains unclear, but a multifactorial origin is suggested with triggering (infections) and maintenance (psychological) factors as well as the persistence of inflammatory (low grade inflammation, microglial activation...), immunologic (decrease of NK cells, abnormal cytokine production, reactivity to a variety of allergens, role of estrogens...) and muscular (mitochondrial dysfunction and failure of bioenergetic performance) abnormalities at the origin of multiple dysfunctions (endocrine, neuromuscular, cardiovascular, digestive...). The complexity of the problem and the sometimes contradictory results of available studies performed so far are at the origin of different pathophysiological and diagnostic concepts. Based on a rigorous analysis of scientific data, the new American concept of Systemic Disease Exertion Intolerance proposed in 2015 simplifies the diagnostic approach and breaks with the past and terminologies (CFS and myalgic encephalomyelitis). It is still too early to distinguish a new disease, but this initiative is a strong signal to intensify the recognition and management of patients with CFS and stimulate research. PMID- 27260788 TI - [Place of azathioprine in the treatment of giant cell arteritis]. AB - OBJECTIVE: The aim of this bicentric retrospective study was to describe the use of azathioprine in giant cell arteritis, and to appreciate its corticosteroid sparing effect in glucocorticoid-dependent patients or with severe glucocorticoid related side effects. METHODS: We retrospectively reviewed the medical records of patients diagnosed with giant cell arteritis between 2000 and 2011 in two departments of internal medicine. Only the patients treated with azathioprine were included in this study. Sociodemographic, clinical, biological, radiological and therapeutic data were collected by a standardized questionnaire. A comparative analysis of daily prednisone dose at the initiation and 1 year after the prescription of azathioprine was made. RESULTS: Of the 28 patients included, 21 responded to azathioprine. At 1 year of follow-up after the initiation of azathioprine, 18 patients (64%) were still in sustained response, asymptomatic, without increase in acute phase response laboratory markers, and with a daily dose of prednisone<10 mg. Three patients (11%) experienced a relapse during azathioprine treatment. Mean daily dose of prednisone were 25.4 mg at the time of initiation of azathioprine, and 4.7 mg at 1 year of treatment, suggesting a corticosteroid-sparing effect (P<0.001). Ten patients experienced azathioprine serious side effects, leading to discontinuation of treatment in seven cases. CONCLUSION: Azathioprine may be an alternative treatment for patients with giant cell arteritis requiring prolonged high dose glucocorticoid therapy or developing severe glucocorticoid related side effects. However, given the potential adverse effects of azathioprine, a close monitoring is necessary. PMID- 27260790 TI - IAPRD annual report - 2015. PMID- 27260789 TI - Effects of Bait Presence and Type of Preservative Fluid on Ground and Carrion Beetle Samples Collected by Pitfall Trapping. AB - Pitfall trapping is a sampling technique frequently used by entomologists around the world. However, there exist sampling biases linked to particular trapping designs, which require investigation. In this study, we compared the effects of the type of preservative fluid (propylene glycol or formaldehyde) and the presence of fish bait in pitfall traps on the number of specimens (individuals) collected, the species richness, and the species composition of carabid (Coleoptera: Carabidae) and silphid (Coleoptera: Silphidae) beetle assemblages. Traps containing propylene glycol collected a substantially higher number of individuals of both taxa and a higher number of silphid species compared with traps containing formaldehyde. The use of fish bait in the traps increased the number of individuals collected and the number of species collected for silphid beetles but had no effect on the collection parameters for carabids. The species composition of the carabid assemblages was minimally affected by the presence of fish bait or the type of preservative fluid, whereas the fish bait had a substantial effect on the species composition of silphids. The silphid species that feed directly on vertebrate carcasses were almost completely absent in the nonbaited traps. The results suggest that pitfall traps baited with fish and containing propylene glycol as a preservative fluid are optimal for the simultaneous sampling of carabid and silphid beetles, which both provide important ecosystem services (e.g., predation of pests and decomposition of vertebrate carcasses) and are therefore interesting for ecological research. PMID- 27260791 TI - Cognitive functioning in individuals with Parkinson's disease and traumatic brain injury: A longitudinal study. AB - OBJECTIVE: To examine longitudinal changes in cognition in individuals with Parkinson's disease (PD) with and without a history of traumatic brain injury (TBI). METHODS: Twenty-five PD participants with a history of mild-moderate post acute (>9 months) TBI and 25 demographically-matched PD controls without a history of TBI were administered measures of cognition (Mattis Dementia Rating Scale), mood, and motor functioning at baseline and at a two-year follow-up evaluation. RESULTS: Individuals with PD and a history of TBI evidenced significantly greater decrements in overall cognition over the two year follow-up period compared to those without a history of TBI. Secondary subscale analyses suggest cognitive decrements may be mainly in the area of executive function, while a trend for group differences on the memory subscale was also observed. Groups did not differ on demographic, motor function, disease severity, cognitive, and mood profiles at baseline and evidenced comparable changes in mood and motor symptoms from baseline to follow-up. CONCLUSION: Findings suggest that a history of mild-moderate TBI is a risk factor for cognitive decline in individuals with PD. PMID- 27260792 TI - Common variants in CACNA1C and MDD susceptibility: A comprehensive meta-analysis. AB - Major depressive disorder (MDD) is one of the most common psychiatric disorders with a relatively high heritability (35-40%). Though rs1006737 in the CACNA1C gene showed significant association with MDD in a British large-scale candidate association study, most of the replication analyses with relatively small sample size reported negative association. Moreover, this locus has never been identified in previous genome-wide association studies (GWAS) for MDD. Here, we conducted a comprehensive meta-analysis of the association between CACNA1C variants and MDD risk by combining all published data. Genetic data from one European GWAS and five individual follow-up studies, which include up to 12,629 patients of MDD and 28,653 controls, that is, the largest sample size on CACNA1C to date, were collected. Rs1006737 showed significant association with MDD in the fixed-effect model (Z = 2.56, P = 0.011, OR = 1.08, 95%CI = 1.04-1.12) and the association remained after reanalyzing the data according to ethnicity. We additionally analyzed other 25 SNPs, genotyped in only one replication study, across the CACNA1C locus, and found that two SNPs, rs4765905 (P = 0.041, OR = 1.05, 95%CI 1.00-1.09) and rs4765937 (P = 0.025, OR = 1.05, 95%CI 1.01-1.09) showed nominal association with MDD, while rs2239073 (P = 0.002, OR = 1.07, 95%CI 1.02-1.11) exhibited significant association with MDD, which survived from multiple corrections. Our study provides support for positive association between CACNA1C and MDD; however, the current data suggest the necessity of replication analyses in a larger-scale sample. (c) 2016 Wiley Periodicals, Inc. PMID- 27260793 TI - Standardization of surgical care in a high-volume center improves survival in resected pancreatic head cancer. AB - BACKGROUND: Durable clinical gains in surgical care are frequently reliant on well-developed standardization of practices. We hypothesized that the standardization of surgical management would result in improved long-term survival in pancreatic cancer. METHODS: Seventy-seven consecutive, eligible patients representing all patients who underwent pancreaticoduodenectomy and received comprehensive, long-term postoperative care at the University of Florida were analyzed. Patients were divided into prestandardization and poststandardization groups based on the implementation of a pancreatic surgery partnership, or standardization program. RESULTS: Standardization resulted in a reduction in median length of stay (10 vs 12 days; P = .032), as well as significant gains in disease-free survival (17 vs 11 months; P = .017) and overall survival (OS; 26 vs 16 months; P = .004). The improvement in overall survival remained significant on multivariate analysis (hazard ratio = .46, P = .005). CONCLUSIONS: Standardization of surgical management of pancreatic cancer was associated with significant gains in long-term survival. These results suggest strongly that management of pancreatic head adenocarcinoma be standardized likely by regionalization of care at high performing oncologic surgery programs. PMID- 27260795 TI - Enhanced postoperative recovery pathways in emergency surgery: a randomized controlled clinical trial. PMID- 27260794 TI - Successful modulation of portal inflow by somatostatin in a porcine model of small-for-size syndrome. AB - BACKGROUND: Somatostatin may prevent the small-for-size syndrome in subjects undergoing extended hepatectomy by decreasing portal pressure. METHODS: Twenty pigs underwent 70% hepatectomy (H70 group, n = 7), 90% hepatectomy (H90 group, n = 7), or sham laparotomy (control group, n = 6). Splanchnic hemodynamics was measured before and after an intraoperative infusion of somatostatin. RESULTS: The portal vein flow normalized to liver weight increased in both H70 and H90 groups (from 125 +/- 42 to 342 +/- 82 mL/min/100g, P = .031 and from 140 +/- 46 to 530 +/- 241, P = .016, respectively). The hepatic venous pressure gradient (HVPG) increased in the H90 group only (from 5.5 +/- 5.8 to 13 +/- 4.9 mm Hg, P = .004). Somatostatin decreased portal vein flow normalized to liver weight in both H70 and H90 groups (from 408 +/- 224 to 360 +/- 227 mL/min/100g, P = .031 and from 560 +/- 190 to 466 +/- 189 mL/min/100g, P = .016), and restored a normal HVPG in the H90 group (from 14.3 +/- 4.8 to 7.7 +/- 6.1 mm Hg, P = .047). CONCLUSIONS: Somatostatin restores a normal HVPG in the setting of small-for-size syndrome and can be considered as an effective pharmaceutical modality of portal inflow modulation after extended hepatectomy. PMID- 27260796 TI - Mesh vs suture cruroplasty in laparoscopic large hiatal hernia repair. PMID- 27260797 TI - David Oliver: Values statements aren't worth the paper. PMID- 27260800 TI - Supporting the Student's Graduated Independence in Diabetes Care. AB - The gradual progression to self-management is a critical milestone for children/adolescents with diabetes. This article provides recommendations to facilitate collaboration between the student's family, diabetes healthcare provider, and school nurse to support and implement a plan that enables the child/adolescent to acquire the skills and knowledge necessary to successfully transition to independent management of diabetes. PMID- 27260799 TI - Genomic profiling of exogenous abscisic acid-responsive microRNAs in tomato (Solanum lycopersicum). AB - BACKGROUND: Plant microRNAs (miRNAs) are involved in various biological pathways and stress responses as negative regulators at the posttranscriptional level. Abscisic acid (ABA) is a key signaling molecule that mediates plant stress response by activating many stress-related genes. Although some miRNAs in plants are previously identified to respond to ABA, a comprehensive profile of ABA responsive miRNAs has not yet been elucidated. RESULTS: Here, we identified miRNAs responding to exogenous application of ABA, and their predicted target genes in the model plant organism tomato (Solanum lycopersicum). Deep sequencing of small RNAs from ABA-treated and untreated tomatoes revealed that miRNAs can be up- or down-regulated upon treatment with ABA. A total of 1067 miRNAs were detected (including 365 known and 702 candidate novel miRNAs), of those, 416 miRNAs which had an abundance over two TPM (transcripts per million) were selected for differential expression analysis. We identified 269 (180 known and 89 novel) miRNAs that respond to exogenous ABA treatment with a change in expression level of |log2FC|>=0.25. 136 of these miRNAs (90 known and 46 novel) were expressed at significantly different levels |log2FC|>=1 between treatments. Furthermore, stem-loop RT-PCR was applied to validate the RNA-seq data. Target prediction and analysis of the corresponding ABA-responsive transcriptome data uncovered that differentially expressed miRNAs are involved in condition stress and pathogen resistance, growth and development. Among them, approximately 90 miRNAs were predicted to target transcription factors and pathogen resistance genes. Some miRNAs had functional overlap in biotic and abiotic stress. Most of these miRNAs were down-regulated following exposure to exogenous ABA, while their related target genes were inversely up-regulated, which is consistent with their negative regulatory role in gene expression. CONCLUSIONS: Exogenous ABA application influences the composition and expression level of tomato miRNAs. ABA mainly down-regulates miRNAs that their target genes involve in abiotic stress adaption and disease resistance. ABA might increase expression of stress-related genes via miRNA-mediated posttranscriptional regulation, and our results indicate that ABA treatment has the potential to improve both abiotic stress tolerance and pathogen resistance. This study presents a comprehensive profile of ABA-regulated miRNAs in the tomato, and provides a robust database for further investigation of ABA regulatory mechanisms. PMID- 27260798 TI - Copy number analysis of whole-genome data using BIC-seq2 and its application to detection of cancer susceptibility variants. AB - Whole-genome sequencing data allow detection of copy number variation (CNV) at high resolution. However, estimation based on read coverage along the genome suffers from bias due to GC content and other factors. Here, we develop an algorithm called BIC-seq2 that combines normalization of the data at the nucleotide level and Bayesian information criterion-based segmentation to detect both somatic and germline CNVs accurately. Analysis of simulation data showed that this method outperforms existing methods. We apply this algorithm to low coverage whole-genome sequencing data from peripheral blood of nearly a thousand patients across eleven cancer types in The Cancer Genome Atlas (TCGA) to identify cancer-predisposing CNV regions. We confirm known regions and discover new ones including those covering KMT2C, GOLPH3, ERBB2 and PLAG1 Analysis of colorectal cancer genomes in particular reveals novel recurrent CNVs including deletions at two chromatin-remodeling genes RERE and NPM2 This method will be useful to many researchers interested in profiling CNVs from whole-genome sequencing data. PMID- 27260801 TI - Whole School, Whole Community, Whole Child-Calling School Nurses to Action. AB - The Whole School, Whole Community, Whole Child model released in 2015 as a collaboration between associations focuses renewed attention on the importance of improved physical, emotional, and social health to student learning. The model replaces and expands upon the Coordinated School Health Model that has been widely implemented in schools since the late 1980s. NASN celebrates this new model and calls school nurses to action in advocating for the implementation of this model in their communities. This article not only introduces this new model to school nurses but shares examples of school nurse advocacy initiatives. PMID- 27260802 TI - Age-related changes in mastication are not improved by tongue exercise in a rat model. AB - OBJECTIVES/HYPOTHESIS: Aging results in progressive changes in deglutitive functions, which may be due in part to alterations in muscle morphology and physiology. Mastication is a critical component of bolus formation and swallowing, but aging effects on masticatory function have not been well studied. STUDY DESIGN: The purpose of this study was to 1) quantify the effects of aging on mastication, and 2) determine the effects of tongue exercise on mastication in young adult and old rats. We hypothesized that there would be significant differences in mastication characteristics (number of bites, interval between bites, time to eat) as a function of age, and that tongue exercise would resolve preexercise differences between age groups. METHODS: We expanded the established model of progressive, 8-week tongue exercise to include a mastication measurement: acoustic recordings of vermicelli pasta biting from 17 old and 17 young adult rats, randomized into exercise and control groups. RESULTS: We found the following: 1) Mastication characteristics were impacted by age. Specifically in older rats, there was an increase in time to eat and number of bites and intervals between bites decreased, suggesting increased oral motor-processing requirements for bolus formation. 2) tongue exercise did not impact mastication behaviors in young adult or old rats. CONCLUSION: Tongue exercise may not have been specific enough to result in behavioral changes in mastication or exercise dose may not have been sufficient. Nevertheless, results were noteworthy in expanding the established rat model of aging and have relevant clinical implications for future translation to human populations. LEVEL OF EVIDENCE: NA Laryngoscope, 127:E29-E34, 2017. PMID- 27260803 TI - Cholinesterases as markers of the inflammatory process associated oxidative stress in cattle infected by Babesia bigemina. AB - The objective of this study was to assess the influence of an asymptomatic experimental infection by Babesia bigemina on cholinesterase's as markers of the inflammatory process and biomarkers of oxidative imbalance. For this purpose, eight naive animals were used, as follows: four as controls or uninfected; and four infected with an attenuated strain of B. bigemina. Blood samples were collected on days 0, 7 and 11 post-inoculation (PI). Parasitemia was determined by blood smear evaluation, showing that the infection by B. bigemina resulted in mean 0.725 and 0.025% on day 7 and 11 PI, respectively, as well as mild anemia. The activities of acetylcholinesterase, butyrylcholinesterase and catalase were lower, while levels of thiobarbituric acid reactive substances and superoxide dismutase activity were higher in infected animals, when compared with the control group. This attenuated strain of B. bigemina induced an oxidative stress condition, as well as it reduces the cholinesterases activity in infected and asymptomatic cattle. Therefore, this decrease of cholinesterase in infection by B. bigemina purpose is to inhibit inflammation, for thereby increasing acetylcholine levels, potent anti-inflammatory molecules. PMID- 27260804 TI - Use of an attenuated live Salmonella Typhimurium vaccine on three breeding pig units: A longitudinal observational field study. AB - The study examined the effects of a licensed live Salmonella Typhimurium vaccine, administered to sows and gilts on three commercial pig units experiencing clinical salmonellosis associated with S. Typhimurium or its monophasic variant. After vaccination, clinical salmonellosis resolved and shedding of S. Typhimurium declined markedly and persistently on all breeding or breeding-finishing units, during the one- to two-year monitoring period. On two finishing units supplied in part by one of the vaccinated herds, pigs from the vaccinated herd were less likely to shed Salmonella than those from non-vaccinating herds, and Salmonella counts in faeces were also lower from the vaccine-linked animals. Non-Typhimurium Salmonella serovars were isolated typically in fewer than 10% of samples, and showed no clear temporal changes in frequency. Vaccination of dams alone with S. Typhimurium was associated with reduced shedding of closely-related serovars among all age groups in this commercial setting. PMID- 27260805 TI - The detection of Vaccinia virus confirms the high circulation of Orthopoxvirus in buffaloes living in geographical isolation, Marajo Island, Brazilian Amazon. AB - In Brazil, serologic evidence of Orthopoxvirus (OPV) circulation showed positivity around 20% in cattle, humans, monkeys and rodents. Although OPV seropositivity has been described in buffalo herds in southeastern Brazil, no Vaccinia virus (VACV) (member of genus OPV) outbreaks in buffalo herds have been described in this country. This study aimed to investigate the detection of anti OPV antibodies and to study the OPV genome in Brazilian buffalo herds. Our results demonstrated a high OPV seropositivity in buffalo herds on Marajo Island and molecular data confirmed the circulation of VACV. The geographical isolation conditionmight be a sine qua non condition to explain our results. PMID- 27260806 TI - Prevalence, risk factor analysis, and hematological findings of hemoplasma infection in domestic cats from Valdivia, Southern Chile. AB - Four distinct cat hemoplasma species are recognized worldwide. However, this is the first study to investigate the prevalence, risk factors, and hematological findings of hemoplasmas in cats from Chile. Complete blood count and 16S rRNA real-time PCR for cat hemoplasma species were performed in 384 blood samples from domestic cats in Valdivia, Chile. Among the 384 samples the species-specific prevalence was as follows: 'Candidatus Mycoplasma haemominutum' (7.8%), Mycoplasma haemofelis (4.4%), 'Candidatus Mycoplasma turicensis' (1%), 'Ca. M. haemominutum'+M. haemofelis (0.78%), 'Ca. M. haemominutum'+'Ca. M. turicensis' (0.52%), 'Ca. M. haemominutum'+'Candidatus Mycoplasma haematoparvum' (0.26%) and 'Ca. M. haemominutum'+M. haemofelis+'Ca. M. haematoparvum' (0.26%). Male sex, older age, outdoor access, and FIV status were risk factors for hemoplasmosis. Mycoplasma haemofelis-positive cats had higher mean corpuscular volume and monocyte count. Four hemoplasma species circulate in the cat population of Valdivia. 'Candidatus M. turicensis' and 'Ca. M. haematoparvum' have been reported for the first time in Chilean cats. PMID- 27260807 TI - Virulence traits and antibiotic resistance among enterococci isolated from dogs with periodontal disease. AB - Periodontal disease - PD - is one of the most widespread diseases in dogs, but the role of this odontogenic infection in the dissemination of pathogenic bacteria present in the oral mucosa to other animals or pet owners is understudied. Trying to unveil the putative pathogenicity of enterococci present in the gums of dogs diagnosed with PD, thirty-two animals were investigated during routine visits to a private veterinary clinic. Seventy-one enterococci were recovered and characterized regarding species, genomic variability, virulence traits, antimicrobial resistance and biofilm-forming ability. Isolates were mainly identified as Enterococcus faecalis, with the large majority (95%) being able to produce biofilm. Regarding antibiotic resistance, all dog enterococci were susceptible to ampicillin, amoxicillin/clavulanate, gentamicin 120, imipenem and vancomycin; while distinct levels of resistance were observed for chloramphenicol (10%), erythromycin (20%), streptomycin-300 (35%) and tetracycline (95%). For virulence traits incidence levels of 35% were observed for beta-hemolysis and 25% for cylA, 25% for gelatinase and 35% for gelE; 85% harbor efaAfs and ebpABC; while ace, agg and esp are present respectively in 50, 30 and 10% of the dog-enterococci; efaAfm and acm were detected in all the Enterococcus faecium. Overall, the widespread prevalence of PD in dogs, associated with the close contact between companion animals, other animals and humans, may act as source for the dissemination of opportunistic pathogenic bacteria. Hence, aforementioned data on virulence and resistance features, emphasizes the need for active surveillance measures, such as the diagnose of PD in companion animals during routine visits to the veterinary clinic. PMID- 27260808 TI - Host stress physiology and Trypanosoma haemoparasite infection influence innate immunity in the woylie (Bettongia penicillata). AB - Understanding immune function is critical to conserving wildlife in view of infectious disease threats, particularly in threatened species vulnerable to stress, immunocompromise and infection. However, few studies examine stress, immune function and infection in wildlife. We used a flow cytometry protocol developed for human infants to assess phagocytosis, a key component of innate immunity, in a critically endangered marsupial, the woylie (Bettongia penicillata). The effects of stress physiology and Trypanosoma infection on phagocytosis were investigated. Blood and faecal samples were collected from woylies in a captive facility over three months. Trypanosoma status was determined using PCR. Faecal cortisol metabolites (FCM) were quantified by enzyme immunoassay. Mean phagocytosis measured was >90%. An interaction between sex and FCM influenced the percentage of phagocytosing leukocytes, possibly reflecting the influence of sex hormones and glucocorticoids. An interaction between Trypanosoma status and FCM influenced phagocytosis index, suggesting that stress physiology and infection status influence innate immunity. PMID- 27260809 TI - Differences in leukocyte differentiation molecule abundances on domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) neutrophils identified by flow cytometry. AB - Although both domestic sheep (DS) and bighorn sheep (BHS) are affected by similar respiratory bacterial pathogens, experimental and field data indicate BHS are more susceptible to pneumonia. Cross-reactive monoclonal antibodies (mAbs) for use in flow cytometry (FC) are valuable reagents for interspecies comparative immune system analyses. This study describes cross-reactive mAbs that recognize leukocyte differentiation molecules (LDMs) and major histocompatibility complex antigens on DS and BHS leukocytes. Characterization of multichannel eosinophil autofluorescence in this study permitted cell-type specific gating of granulocytes for evaluating LDMs, specifically on neutrophils, by single-label FC. Evaluation of relative abundances of LDMs by flow cytometry revealed greater CD11a, CD11b, CD18 (beta2 integrins) and CD 172a (SIRPalpha) on DS neutrophils and greater CD14 (lipopolysaccharide receptor) on BHS neutrophils. Greater CD25 (IL-2) was identified on BHS lymphocytes following Concavalin A stimulation. While DS and BHS have similar total peripheral blood leukocyte counts, BHS have proportionately more neutrophils. PMID- 27260810 TI - Oral yeast colonization in peritoneal dialysis and hemodialysis patients and renal transplant recipients. AB - OBJECTIVE: We aimed to investigate the frequency of oral yeast colonization (OYC) and the risk factors for patients who received continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) or were renal transplant recipients (RTRs). The patients admitted to the Nephrology Clinic at Ataturk University Medical School from January through April 2013 were included in the study. A questionnaire about risk factors was filled out, and swab cultures were taken from the tongue surface of each participant. OYC was detected in 32.1% of the RTRs, 40% of the HD patients, 20.9% of the CAPD patients, and 18% of the healthy control (HC) group. Of the 42 yeast strains isolated from the renal replacement therapy groups, 26 strains (61.9%) were Candida albicans, nine (21.4%) were Candida glabrata, two (4.7%) were Candida krusei, two (4.7%) were Candida kefyr, one (2.38%) was Candida parapsilosis, and two (4.7%) were Geotrichum candidum. Risk factors for OYC in the RTRs group included antibiotic use and the presence of dental prostheses; however, in patients with chronic renal failure undergoing CAPD, only the presence of dental prostheses was found to be a statistically significant risk factor. Although OYC was mostly detected in patients with chronic kidney disease (undergoing HD, a variety of isolated yeast strains in the RTRs was noted. The rates of OYC and isolated Candida species in CAPD were similar to those of the HC group. PMID- 27260811 TI - Evidence of multiple reassortment events of feline-to-human rotaviruses based on a rare human G3P[9] rotavirus isolated from a patient with acute gastroenteritis. AB - A rare human/feline-like rotavirus G3P[9] strain, CAU14-1-262, from a 2-year-old girl with severe gastroenteritis was isolated and sequenced. The 11 gene segments of the CAU14-1-262 strain possessed a novel genotype constellation, G3-P[9]-I3-R3 C3-M3-A3-N3-T1-E3-H6, which was identified for the first time. Phylogenetic analysis of this strain identified the following genome origins: VP7, VP4, VP6, VP1-VP3, NSP1, NSP2, and NSP4 genes possessed an AU-1-like genotype 3 constellation with high sequence identity to those of the feline and human/feline like rotaviruses; NSP5 possessed a H6 lineage, with highest sequence identity to the human/feline-like E2541 strain; and the NSP3 gene possessed a Wa-like genotype 1 constellation with high sequence identity to those of the of human rotaviruses. These results provided evidence of multiple reassortment events in G3P[9] rotavirus CAU14-1-262 and possibility of feline-to-human interspecies transmission. PMID- 27260812 TI - Isolation and genetic characterization of swinepox virus from pigs in India. AB - Swinepox virus (SWPV), a member of the genus Suipoxvirus causes generalized pock like lesions on the body of domestic and wild pigs. Although outbreak has been reported in India since 1987, virus isolation and genetic characterization remained elusive. In September 2013, an outbreak of acute skin infection occurred in piglets in a commercial piggery unit at Rohtak district in Haryana, India. The presence of SWPV in scab samples collected from piglets succumbed to infection was confirmed by virus isolation, PCR amplification of SWPV-specific gene segments and nucleotide sequencing. Phylogenetic analysis of host-range genes of the SWPV revealed that the Indian isolate is genetically closely related to reference isolate SWPV/pig/U.S.A/1999/Nebraska. To the best of our knowledge this is the first report on isolation and genetic characterization of SWPV from pigs in India. PMID- 27260813 TI - Diagnosing feline immunodeficiency virus (FIV) infection in FIV-vaccinated and FIV-unvaccinated cats using saliva. AB - We recently showed that two immunochromatography point-of-care FIV antibody test kits (Witness FeLV/FIV and Anigen Rapid FIV/FeLV) were able to correctly assign FIV infection status, irrespective of FIV vaccination history, using whole blood as the diagnostic specimen. A third FIV antibody test kit, SNAP FIV/FeLV Combo (an enzyme-linked immunosorbent assay [ELISA]), was unable to differentiate antibodies produced in response to FIV vaccination from those incited by FIV infection. The aim of this study was to determine if saliva is a suitable diagnostic specimen using the same well characterized feline cohort. FIV infection status of these cats had been determined previously using a combination of serology, polymerase chain reaction (PCR) testing and virus isolation. This final assignment was then compared to results obtained using saliva as the diagnostic specimen utilizing the same three point-of-care FIV antibody test kits and commercially available PCR assay (FIV RealPCR). In a population of cats where one third (117/356; 33%) were FIV-vaccinated, both immunochromatography test kits accurately diagnosed FIV infection using saliva via a centrifugation method, irrespective of FIV vaccination history. For FIV diagnosis using saliva, the specificity of Anigen Rapid FIV/FeLV and Witness FeLV/FIV was 100%, while the sensitivity of these kits was 96% and 92% respectively. SNAP FIV/FeLV Combo respectively. SNAP FIV/FeLV Combo had a specificity of 98% and sensitivity of 44%, while FIV RealPCR testing had a specificity of 100% and sensitivity of 72% using saliva. A revised direct method of saliva testing was trialed on a subset of FIV-infected cats (n=14), resulting in 14, 7 and 0 FIV positive results using Anigen Rapid FIV/FeLV, Witness FeLV/FIV and SNAP FIV/FeLV Combo, respectively. These results demonstrate that saliva can be used to diagnose FIV infection, irrespective of FIV vaccination history, using either a centrifugation method (Anigen Rapid FIV/FeLV and Witness FeLV/FIV) or a direct method (Anigen Rapid FIV/FeLV). Collection of a saliva specimen therefore provides an acceptable alternative to venipuncture (i) in fractious cats where saliva may be easier to obtain than whole blood, (ii) in settings when a veterinarian or trained technician is unavailable to collect blood and (iii) in shelters where FIV testing is undertaken prior to adoption but additional blood testing is not required. PMID- 27260814 TI - High prevalence of "Candidatus Rickettsia amblyommii" in Amblyomma ticks from a Spotted Fever Endemic Region in North Argentina. AB - Ticks from an endemic Spotted Fever region in Argentina were analysed by PCR for Spotted Fever Group Rickettsiae. DNA of "Candidatus Rickettsia amblyommii" was found in 21.3% of Amblyomma hadanii and in 44.0% of A. neumanni. Amblyomma sculptum (formerly A. cajennense) and Haemaphysalis juxtakochi were negative for rickettsial DNA. DNA of Rickettsia rickettsii, the etiological agent of the clinical cases reported within the studied region was not detected in the analysed sample. PMID- 27260815 TI - Non-response to daclatasvir and asunaprevir therapy in patients co-infected with hepatitis C virus genotypes 1 and 2. AB - Direct-acting antiviral agents for hepatitis C virus (HCV) have been developed such as combined daclatasvir (DCV) and asunaprevir (ASV) treatment. This typically enables HCV serotype 1 patients to achieve a high sustained virological response rate, but a small number of such patients fail to respond to therapy. We investigated three HCV patients who showed no response to DCV and ASV therapy. Hepatitis C genotyping was undertaken in the three patients using nested polymerase chain reaction and polymerase chain reaction direct sequencing in the core region of the HCV genome. All three patients possessed HCV serotype 1, and no mutations were identified in either the non-structural protein 3 or 5A region. The three patients were shown to be co-infected with HCV genotypes 1 and 2 because genotypes 2a and 2b were also identified. This is the first report into failed response to DCV and ASV therapy in patients co-infected with HCV genotypes 1 and 2. PMID- 27260816 TI - The functioning of the Medical Council of India analysed by the Parliamentary Standing Committee of Health and Family Welfare. AB - On March 8, 2016, the 92nd report on the functioning of the Medical Council of India (MCI) (1) was placed before both Houses of Parliament by Professor Ram Gopal Yadav, Chairman of the Parliamentary Standing Committee of Health and Family Welfare. PMID- 27260817 TI - The Chennai floods of 2015 and the health system response. AB - The Chennai floods of 2015 were a calamity of unexpected proportions (1). The impact on the lives of the poor has been immense. Thousands needed to abandon their already precarious dwellings on the banks of the Adyar River, and other low lying areas for temporary shelters. The differential experience and impact of disasters on different segments of the population helps understand the dynamics of sociopolitical structures and supports. PMID- 27260818 TI - Ethical dilemmas among dental professionals in Davangere city- a cross-sectional survey. AB - To determine the ethical problems faced by dental practitioners, a cross sectional survey was conducted in Bapuji Dental College and Hospital, College of Dental Sciences and private dental clinics in the city of Davangere. A questionnaire with close-ended questions on eight scenarios was administered to the 135 study participants. In the case of scenario 1, 81.4% of the participants said that the doctor had violated the principle of truthfulness. As for scenario 2, less than 50% of the participants replied that the doctor had breached ethical principles. In case scenario 3, 93% felt that the doctor should have taken the physician's opinion before extracting a tooth. Most dental practitioners faced ethical dilemmas because of the lack of awareness, and there is a need to introduce certain programmes to promote knowledge of ethics. PMID- 27260819 TI - The Chennai floods of 2015: urgent need for ethical disaster management guidelines. AB - India has suffered several natural disasters in recent years. The super cyclone of Orissa in 1999 and the tsunami on the southeastern coast in 2004, both led to major developments in disaster management abilities in the country. Almost a decade after the last major disaster that hit south India, the recent floods in Chennai in 2015 brought to the fore a whole set of ethical considerations. There were issues of inequity in the relief and response activities, conflicts and lack of coordination between the government and non-government relief and response, more emphasis on short-term relief activities rather than rehabilitation and reconstruction, and lack of crisis standards of care in medical services. This paper highlights these ethical issues and the need for ethical guidelines and an ethical oversight mechanism for disaster management and response. PMID- 27260820 TI - Robert Spitzer and psychiatric classification: technical challenges and ethical dilemmas. AB - Dr Robert Leopold Spitzer (May 22, 1932-December 25, 2015), the architect of modern psychiatric diagnostic criteria and classification, died recently at the age of 83 in Seattle. Under his leadership, the American Psychiatric Association's (APA) Diagnostic and Statistical Manuals (DSM) became the international standard. PMID- 27260821 TI - Ethics tries handling inner conflicts scientifically/spiritually. AB - "Ethic: from ethos, character, L ethos, adopted by English especially in sense of 'character and spirit of a people'. Intimately akin to Gr ethos, custom, Skt. sva dha one's own doing or action; sva self (cf suicide) + dha to self." "Sva dha:self-position, self-power, inherent power, custom, rule, ease, comfort, according to one's habit or pleasure, spontaneously, willingly, easily, freely, undisturbedly, wantonly, sportively." Words reveal their meanings to those who establish intimacy with them, as the bride unveils her face only to the beloved one. PMID- 27260822 TI - Tubal sterilisation without consent: a case report. AB - INTRODUCTION: Tubal sterilisation is practised all over the world. This safe, easy and highly effective, long-term method for birth control can be carried out during the hospital stay for either a normal delivery or caesarean section. In India, female sterilisation accounts for 37.3% of all methods of family planning. PMID- 27260823 TI - Tubal ligation on an unmarried girl: How and why? AB - After going through the case report, it seems there can be two possible explanations for the tubal ligation performed without the consent of the patient: first, absolute malafide intent and second, a medical mix-up with tragic long term consequences for the girl. PMID- 27260824 TI - The ethics of research on stored biological samples: outcomes of a Workshop. AB - Research is often conducted using laboratory samples and data. The ethical issues that arise in a study involving residual samples are considerably different from those arising in a prospective study. Some of these ethical issues concern the risks to confidentiality, individual autonomy, trust in and credibility of the researcher or the research, commercialisation and even the nomenclature involved. PMID- 27260825 TI - Diary of a daughter. AB - This is a personal account of my struggle as a young medical student after my mother was diagnosed with an incurable illness; she subsequently passed away. Through this story, I share my experience with the medical profession from the perspective of the daughter of a terminally ill mother. PMID- 27260826 TI - Ethical dilemmas of medically unexplained symptoms. AB - Medically unexplained symptoms (MUS) are common across health settings. These are defined as "physical symptoms that prompt sufferer to seek healthcare but remain unexplained after an appropriate medical evaluation". Expectedly, MUS are often associated with significant health-seeking behaviours that add to the burden on health resources. PMID- 27260827 TI - Interpretation: a confounding factor. AB - With reference to the article "Passive euthanasia in India: a critique", authored by Ms Rohini Shukla and published online on August 5, 2015, I would like to make a few comments and highlight the following points. First, the author notes that Section 309 IPC has been decriminalised. This is not so since there has neither been any amendment to the IPC, nor has any ordinance been passed regarding the matter. Attempting suicide is still an offence in India. Second, the author observes that withholding life support is an act of omission and withdrawing life support is an act of commission and the terms have been used interchangeably by the Hon'ble Court, although there is a subtle difference between the two terms. PMID- 27260828 TI - Milestones for the Final Mile: Interspecialty Distinctions in Primary Palliative Care Skills Training. AB - CONTEXT: Primary palliative care (PPC) skills are useful in a wide variety of medical and surgical specialties, and the expectations of PPC skill training are unknown across graduate medical education. OBJECTIVES: We characterized the variation and quality of PPC skills in residency outcomes-based Accreditation Council for Graduate Medical Education (ACGME) milestones. METHODS: We performed a content analysis with structured implicit review of 2015 ACGME milestone documents from 14 medical and surgical specialties chosen for their exposure to clinical situations requiring PPC. For each specialty milestone document, we characterized the variation and quality of PPC skills in residency outcomes-based ACGME milestones. RESULTS: We identified 959 occurrences of 29 palliative search terms within 14 specialty milestone documents. Within these milestone documents, implicit review characterized 104 milestones with direct saliency to PPC skills and 196 milestones with indirect saliency. Initial interrater agreement of the saliency rating among the primary reviewers was 89%. Specialty milestone documents varied widely in their incorporation of PPC skills within milestone documents. PPC milestones were most commonly found in milestone documents for Anesthesiology, Pediatrics, Urology, and Physical Medicine and Rehabilitation. PPC-relevant milestones were most commonly found in the Interpersonal and Communication Skills core competency with 108 (36%) relevant milestones classified under this core competency. CONCLUSIONS: Future revisions of specialty specific ACGME milestone documents should focus on currently underrepresented, but important PPC skills. PMID- 27260829 TI - Human papillomavirus and anal carcinoma knowledge in men who have sex with men in Belgrade, Serbia. AB - BACKGROUND: To evaluate the level of knowledge among men who have sex with men regarding human papillomavirus (HPV), anal cancer screening, and HPV vaccine. METHODS: A cross-sectional study was conducted in 2013 in Belgrade, Serbia, comprising 142 HIV-positive and 128 HIV-negative persons. RESULTS: Of all participants, 34.8% had never heard of HPV infection; 43.3% of participants were informed that HPV infection might be asymptomatic, while 30.4% knew that HPV is not transmitted by towels/cloth. Furthermore, 45.9% answered that HPV is a cause of genital warts, while 28.9%, 14.4%, and 17.4%, respectively, answered that it can cause anal, penile, and oral cancers. Only one-fourth of participants knew that anal cancer is more frequent in homosexual men. More than 50% had not heard of anal Papanicolaou (Pap) smears, and less than 3% had ever had it. Almost 90% of participants did not know which physicians provide anal Pap smears. Less than one-third knew that regular anal Pap smears might prevent consequences of anal HPV infection. The majority of participants did not know that there is a vaccine against HPV and anal cancer. Less than 50% reported willingness to receive HPV vaccine. Knowledge was slightly better in HIV-positive men in comparison with HIV negative ones. CONCLUSIONS: Results point out the need for community efforts to promote knowledge about HPV, anal carcinoma, and anal Pap screening among men who have sex with men and their healthcare providers, and to increase the acceptance of HPV vaccine by the population. PMID- 27260830 TI - Care coordination, medical complexity, and unmet need for prescription medications among children with special health care needs. AB - BACKGROUND: Children with special health care needs (CSHCN) have multiple unmet health care needs including that of prescription medications. OBJECTIVES: The objectives of this study were twofold: 1) to quantify and compare unmet needs for prescription medications for subgroups of CSHCN without and with medical complexity (CMC)-those who have multiple, chronic, and complex medical conditions associated with severe functional limitations and high utilization of health care resources, and 2) to describe its association with receipt of effective care coordination services and level of medical complexity. METHOD: A secondary data analysis of the 2009/2010 National Survey of CSHCN, a nationally representative telephone survey of parents of CSHCN, was conducted. Logistic regression models were constructed to determine associations between unmet need for prescription medications and medical complexity and care coordination for families of CSHCN, while controlling for demographic variables such as race, insurance, education level, and household income. Analyses accounted for the complex survey design and sampling weights. RESULTS: CMC represented about 3% of CSHCN. CMC parents reported significantly more unmet need for prescription medications and care coordination (4%, 68%), compared to Non-CMC parents (2%, 40%). Greater unmet need for prescription medications was associated with unmet care coordination (adjusted OR 3.81; 95% CI: 2.70-5.40) and greater medical complexity (adjusted OR 2.01; 95% CI: 1.00-4.03). CONCLUSIONS: Traditional care coordination is primarily facilitated by nurses and nurse practitioners with little formal training in medication management. However, pharmacists are rarely part of the CSHCN care coordination model. As care delivery models for these children evolve, and given the complexity of and numerous transitions of care for these patients, pharmacists can play an integral role to improve unmet needs for prescription medications. PMID- 27260831 TI - Characterizing the collagen stabilizing effect of crosslinked chitosan nanoparticles against collagenase degradation. AB - Antibacterial and chelating properties of chitosan has been widely studied for various dental applications. OBJECTIVE: To characterize the interaction between chitosan-nanoparticles (CSnp) and collagen, and understand their stabilizing effect against collagenase degradation for dentin matrix stabilization. METHODS: Phase-1: a single Type I collagen-fibril model was used to study the interaction with CSnp along with carbodiimides crosslinking treatment. Degradation of the crosslinked fibrils was studied with bacterial collagenase enzyme and monitored using Fourier Transform Infrared (FTIR) spectroscopy, turbidity measurement (400nm), ninhydrin assay and Atomic Force Microscopy (AFM). Interaction of CSnp with collagenase and Type I collagen, were evaluated using SDS-PAGE, and proteolytic cleavage potential of a synthetic peptide. Phase-2: degradation of dentin collagen crosslinked with/without CSnp was evaluated using FTIR, ninhydrin assay and Scanning Electron Microscopy (SEM). Glutaraldehyde crosslinking was used as a positive control. RESULTS: Both native collagen-fibrils and dentin collagen after crosslinking showed higher resistance to collagenase degradation, as observed in turbidity measurements and FTIR spectra. AFM images showed the interaction of CSnp with single collagen-fibril and crosslinked collagen resisted collagenase degradation up to 54h. The collagen and collagenase both formed complexes with CSnp resulting in thickening of bands and reduction in collagen degradation. CSnp treated collagenase showed significantly reduced cleavage of the fluorescent peptides. Dentin collagen was coated with CSnp following crosslinking with significant increase in resistance to collagenase degradation. SIGNIFICANCE: Crosslinked CSnp on collagen stabilized and enhanced the resistance of dentin matrix against bacterial collagenase degradation due to non-specific interaction with both collagen and collagenase. PMID- 27260832 TI - The Clinical Spectrum of Zika Virus in Returning Travelers. AB - INTRODUCTION: The clinical spectrum of Zika virus had, to date, been described in small series from endemic/epidemic countries and is not well established. METHODS: We describe the clinical manifestations of laboratory-proven Zika virus infection in Israeli travelers during December 2015-February 2016, and review all published cases of travel-related Zika virus. RESULTS: During the study period, 8 returning Israeli travelers were diagnosed with Zika virus infection. In addition, 41 published cases were included, mostly from Latin America to Europe and North America. Overall, 65.3% were diagnosed by polymerase chain reaction. Rash was the most frequent symptom, present in 95.7% of cases, followed by fever and arthralgia. Conjunctivitis was present in 53.1%; however, only 40.3% presented with a triad of conjunctivitis, fever, and rash. Less frequent symptoms included dysgeusia and nightmares, which, together with arthralgia, persisted for several weeks in some travelers. CONCLUSIONS: Zika virus clinical picture in travelers is diverse. Prolonged symptoms may occur. PMID- 27260833 TI - An Unexpected Pneumonitis. PMID- 27260834 TI - A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant. AB - Episodic ataxia 2 (EA2) is an autosomal dominant disorder caused by mutations in the gene CACNA1A that encodes the pore-forming CaV2.1 calcium channel subunit. The majority of EA2 mutations reported so far are nonsense or deletion/insertion mutations predicted to form truncated proteins. Heterologous expression of wild type CaV2.1, together with truncated constructs that mimic EA2 mutants, significantly suppressed wild-type calcium channel function, indicating that the truncated protein produces a dominant-negative effect (Jouvenceau et al., 2001; Page et al., 2004). A similar finding has been shown for CaV2.2 (Raghib et al., 2001). We show here that a highly conserved sequence in the cytoplasmic N terminus is involved in this process, for both CaV2.1 and CaV2.2 channels. Additionally, we were able to interfere with the suppressive effect of an EA2 construct by mutating key N-terminal residues within it. We postulate that the N terminus of the truncated channel plays an essential part in its interaction with the full-length CaV2.1, which prevents the correct folding of the wild-type channel. In agreement with this, we were able to disrupt the interaction between EA2 and the full length channel by co-expressing a free N-terminal peptide. PMID- 27260835 TI - Mitochondrial DNA in CSF distinguishes LRRK2 from idiopathic Parkinson's disease. AB - Mitochondrial DNA regulates mitochondrial function which is altered in both idiopathic and familial forms of Parkinson's disease. To investigate whether these two disease forms exhibit an altered regulation of mitochondrial DNA we measured cell free mitochondrial DNA content in cerebrospinal fluid (CSF) from idiopathic and LRRK2-related Parkinson's disease patients. The concentration of mitochondrial DNA was measured using a digital droplet polymerase chain reaction technique in a total of 98 CSF samples from a cohort of subjects including: 20 LRRK2(G2019S) mutation carriers with Parkinson's disease, 26 asymptomatic LRRK2(G2019S) mutation carriers, 31 patients with idiopathic Parkinson's disease and 21 first-degree relatives of LRRK2 Parkinson's disease patients without the mutation. Here we report that LRRK2(G2019S) mutation carriers with Parkinson's disease exhibit a high concentration of mitochondrial DNA in CSF compared with asymptomatic LRRK2(G2019S) mutation carriers and with idiopathic Parkinson's disease patients. In addition, idiopathic, but not LRRK2 Parkinson's disease is associated with low CSF concentration of alpha-synuclein. These results show that high mitochondrial DNA content in CSF distinguishes idiopathic from LRRK2-related Parkinson's disease suggesting that different biochemical pathways underlie neurodegeneration in these two disorders. PMID- 27260836 TI - Level of PICALM, a key component of clathrin-mediated endocytosis, is correlated with levels of phosphotau and autophagy-related proteins and is associated with tau inclusions in AD, PSP and Pick disease. AB - Single nucleotide polymorphisms in PICALM, a key component of clathrin-mediated endocytosis machinery, have been identified as genetic susceptibility loci for late onset Alzheimer's disease (LOAD). We previously reported that PICALM protein levels were decreased in AD brains and that PICALM was co-localised with neurofibrillary tangles in LOAD, familial AD with PSEN1 mutations and Down syndrome. In the present study, we analysed PICALM expression, cell localisation and association with pathological cellular inclusions in other tauopathies and in non-tau related neurodegenerative diseases. We observed that PICALM was associated with neuronal tau pathology in Pick disease and in progressive supranuclear palsy (PSP) and co-localised with both 3R and 4R tau positive inclusions unlike in corticobasal degeneration (CBD) or in frontotemporal lobar degeneration (FTLD)-MAPT P301L. PICALM immunoreactivities were not detected in tau-positive tufted astrocytes in PSP, astrocytic plaques in CBD, Lewy bodies in Lewy body disease, diffuse type (LBD) and in TDP-43-positive inclusions in FTLD. In the frontal cortex in tauopathies, the ratio of insoluble to soluble PICALM was increased while the level of soluble PICALM was decreased and was inversely correlated with the level of phosphotau. PICALM decrease was also significantly correlated with increased LC3-II and decreased Beclin-1 levels in tauopathies and in non-tau related neurodegenerative diseases. These results suggest that there is a close relationship between abnormal PICALM processing, tau pathology and impairment of autophagy in human neurodegenerative diseases. PMID- 27260837 TI - Cognitive deficits triggered by early life stress: The role of histone deacetylase 1. AB - Studies showed that histone deacetylase (HDAC) inhibitors can reverse cognitive deficits found in neurodegenerative disorders and age-related memory decline. However, the role of HDACs in stress-induced cognitive deficits has not been investigated. In the stress-susceptible mouse strain Balb/c, early life stress triggers a persistent decrease in HDAC expression in the forebrain neocortex, including reduced expression of class I HDACs. The same mice show pronounced cognitive deficits in adulthood, namely deficits in working memory and attention set-shifting. Here we show that these mice also exhibit reduced association of HDAC1 with promotor III of the brain-derived neurotrophic factor (Bdnf) gene, and that cognitive testing leads to abnormally increased Bdnf mRNA expression. A pharmacological reduction of Bdnf-tropomyosine kinase B receptor signaling effectively reverses the cognitive deficits, indicating that enhanced transcriptional activation of the Bdnf gene contributes to their emergence. In contrast to Balb/c mice, C57Bl/6 mice only develop attention set-shifting deficits when raised by Balb/c foster mothers during the time the pups are exposed to early life stress. HDAC1 levels at Bdnf promotor III are unaltered in such C57Bl/6 mice, although they exhibit decreased levels of HDAC1 at the promotor of the early-growth response gene 2 (Egr2) and abnormally increased Egr2 mRNA expression after cognitive testing. Hence, contrary to the beneficial effects of HDAC inhibition in neurodegenerative diseases, the reduced HDAC1 levels at promotors of distinct plasticity-associated genes predispose animals exposed to early life stress to enhanced expression of these genes upon cognitive challenge, an effect that negatively influences cognitive task performance. PMID- 27260838 TI - Pathological conformations involving the amino terminus of tau occur early in Alzheimer's disease and are differentially detected by monoclonal antibodies. AB - Conformational changes involving the amino terminus of the tau protein are among the earliest alterations associated with tau pathology in Alzheimer's disease and other tauopathies. This region of tau contains a phosphatase-activating domain (PAD) that is aberrantly exposed in pathological forms of the protein, an event that is associated with disruptions in anterograde fast axonal transport. We utilized four antibodies that recognize the amino terminus of tau, TNT1, TNT2 (a novel antibody), Tau12, and Tau13, to further study this important region. Using scanning alanine mutations in recombinant tau proteins, we refined the epitopes of each antibody. We examined the antibodies' relative abilities to specifically label pathological tau in non-denaturing and denaturing assays to gain insight into some of the mechanistic details of PAD exposure. We then determined the pattern of tau pathology labeled by each antibody in human hippocampal sections at various disease stages in order to characterize PAD exposure in the context of disease progression. The characteristics of reactivity for the antibodies fell into two groups. TNT1 and TNT2 recognized epitopes within amino acids 7-12 and specifically identified recombinant tau aggregates and pathological tau from Alzheimer's disease brains in a conformation-dependent manner. These antibodies labeled early pre-tangle pathology from neurons in early Braak stages and colocalized with thiazine red, a marker of fibrillar pathology, in classic neurofibrillary tangles. However, late tangles were negative for TNT1 and TNT2 indicating a loss of the epitope in later stages of tangle evolution. In contrast, Tau12 and Tau13 both identified discontinuous epitopes in the amino terminus and were unable to differentiate between normal and pathological tau in biochemical and tissue immunohistological assays. Despite the close proximity of these epitopes, the antibodies demonstrated remarkably different abilities to identify pathological changes in tau indicating that detection of conformational alterations involving PAD exposure is not achieved by all N-terminal tau antibodies and that a relatively discrete region of the N-terminus (i.e., amino acids 7-12, the TNT1 and TNT2 epitope) is central to the differences between normal and pathological tau. The appearance of PAD in early tau pathology and its disappearance in late-stage tangles suggest that toxic forms of tau are associated with the earliest forms of tau deposits. Collectively, these findings demonstrate that the TNT antibodies are useful markers for early conformational display of PAD and provide information regarding conformational changes that have potential implications in the toxic mechanisms of tau pathology. PMID- 27260840 TI - Erratum to "Predictors and Rates of Delayed Symptomatic Hyponatremia after Transsphenoidal Surgery: A Systematic Review" [World Neurosurg. 88 (2016) 1-6]. PMID- 27260839 TI - Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants. AB - OBJECTIVE: To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection. STUDY DESIGN: We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses. RESULTS: Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital acquired infections was 50% lower in the TLf group compared with the placebo group (P < .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing <1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period. CONCLUSION: We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00854633. PMID- 27260841 TI - Serum response factor provokes epithelial-mesenchymal transition in renal tubular epithelial cells of diabetic nephropathy. AB - We investigated the role of serum response factor (SRF) in epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs) in diabetic nephropathy (DN). The expression of SRF, epithelial markers (E-cadherin and ZO-1), and mesenchymal markers (fibronectin, collagen-1, alpha-SMA, FSP-1) was examined in human proximal renal tubular epithelial cells (HK-2 cells) or renal medulla tissues following high glucose. SRF was upregulated by SRF plasmids and downregulated by CCG-1423 (a small molecule inhibitor of SRF) to investigate how SRF influenced EMT in TECs of DN. Streptozotocin was used to generate DM in rats. In HK-2 cells after high-glucose treatment and renal medulla tissues of diabetic rats, SRF, fibronectin, collagen-1, alpha-SMA, and FSP-1 increased, while E cadherin and ZO-1 declined. SRF overexpression in HK-2 cells induced expression of Snail, an important transcription factor mediating EMT. Blockade of SRF by CCG 1423 reduced Snail induction and protected TECs from EMT both in vitro and in vivo. Together, increased SRF activity promotes EMT in TECs and dysfunction in DN. Targeting SRF by small molecule inhibitor may be an attractive therapeutic strategy for DN. PMID- 27260842 TI - Genome-wide identification of quantitative trait transcripts for blood traits in the liver samples of a White Duroc * Erhualian F2 pig resource population. AB - Blood cell counts are important clinical indicators for health status. The liver plays a crucial role in food digestion and metabolism and is also a blood-forming organ. Here, we conducted a whole-genome quantitative trait transcript (QTT) analysis on 497 liver samples for 16 hematological traits in a White Duroc * Erhualian F2 pig resource population. A total of 20,108 transcripts were explored to detect their association with hematological traits. By using Spearman correlation coefficients, we identified 1,267 QTTs for these 16 hematological traits at the significance threshold of P < 0.001. We found 31 candidate genes for erythrocyte and leukocyte-related traits by a look-up of human and pig genome wide association study results. Furthermore, we constructed coexpression networks for leukocyte-related QTTs using weighted gene coexpression analysis. These QTTs were clustered into two to eight modules. The highest connection strength in intramodules was identified in a module for white blood cell count. In the module, USP18, RSAD2, and OAS1 appeared to be important genes involved in interferon-stimulated innate immune system. The findings improve our understanding of intrinsic relationships between the liver and blood cells and provide novel insights into the potential therapeutic targets of hematologic diseases. PMID- 27260844 TI - Too strong? Barriers from getting support before a suicide attempt in Lithuania. AB - The study aimed to understand the tendencies of help seeking before a suicide attempt in Lithuania. An analysis of interviews with 21 Lithuanian adults demonstrated strong avoidance of seeking help. The main reasons for avoidance included a lack of trust in other people, thinking that one must solve problems independently without sharing them, avoiding troubling others, and a belief that showing genuine emotions is a sign of weakness. These findings may contribute to suicide prevention by more deeply understanding the barriers to help seeking among high suicide risk groups, particularly in countries with a traumatic historical experience. PMID- 27260843 TI - Preeclampsia, of mice and women. AB - Preeclampsia (PE) is a devastating disorder of pregnancy that affects up to 8% of pregnant women in the United States. The diagnosis of PE is made by the presentation of new-onset hypertension, >=140 mmHg systolic blood pressure (BP) or >=90 mmHg diastolic BP, and either proteinuria or another accompanying sign/symptom, such as renal insufficiency, thrombocytopenia, hepatic dysfunction, pulmonary edema, or cerebral/visual. These signs can occur suddenly and without warning. PE that presents before 34 wk of gestation is considered early onset and carries a greater risk for perinatal morbidity/mortality than late-onset PE that occurs at or after 34 wk of gestation. At this time there is no cure for PE, and the only effective treatment is delivery of the baby and placenta. If allowed to progress to eclampsia (PE with neurologic involvement), seizures will occur and possibly death through stroke. PE also carries the risk of significant fetal and neonatal morbidity/mortality in addition to long-term health risks for mother and child. Despite significant research efforts to accurately predict, diagnose, and treat PE, a cure eludes us. Elucidating the pathophysiological mechanisms that can cause PE will aid in our ability to accurately prevent, manage, and treat PE to avoid maternal and fetal losses. Intense research efforts are focused on PE, and the mouse has proven to be a useful animal model for investigating molecular mechanisms that may hold the key to unraveling the mysteries of PE in women. PMID- 27260845 TI - Pseudopilin residue E5 is essential for recruitment by the type 2 secretion system assembly platform. AB - Type II secretion systems (T2SSs) promote secretion of folded proteins playing important roles in nutrient acquisition, adaptation and virulence of Gram negative bacteria. Protein secretion is associated with the assembly of type 4 pilus (T4P)-like fibres called pseudopili. Initially membrane embedded, pseudopilin and T4 pilin subunits share conserved transmembrane segments containing an invariant Glu residue at the fifth position, E5. Mutations of E5 in major T4 pilins and in PulG, the major pseudopilin of the Klebsiella T2SS abolish fibre assembly and function. Among the four minor pseudopilins, only PulH required E5 for secretion of pullulanase, the substrate of the Pul T2SS. Mass spectrometry analysis of pili resulting from the co-assembly of PulG(E5A) variant and PulG(WT) ruled out an E5 role in pilin processing and N-methylation. A bacterial two-hybrid analysis revealed interactions of the full-length pseudopilins PulG and PulH with the PulJ-PulI-PulK priming complex and with the assembly factors PulM and PulF. Remarkably, PulG(E5A) and PulH(E5A) variants were defective in interaction with PulM but not with PulF, and co-purification experiments confirmed the E5-dependent interaction between native PulM and PulG. These results reveal the role of E5 in a recruitment step critical for assembly of the functional T2SS, likely relevant to T4P assembly systems. PMID- 27260846 TI - Management of disappearing colorectal liver metastases. AB - The development of new potent systemic treatment modalities has led to a significant increase in survival of patients with colorectal liver metastases. In the neo-adjuvant setting, these modalities can be used for patient selection, down staging, and conversion from non-resectable to resectable liver metastases. In addition, complete radiological disappearance of metastases can occur, the phenomenon of disappearing liver metastases. Because only a small percentage of these patients (0-8%) have a complete radiological response of all liver metastases, most patients will undergo surgery. At laparotomy, local residual disease at the site of the disappeared metastasis is still found in 11-67%, which highlights the influence of the imaging modalities used at (re)staging. When the region of the disappeared liver metastasis was resected, microscopically residual disease was found in up to 80% of the specimens. Alternatively, conservative management of radiologically disappeared liver metastases resulted in 19-74% local recurrence, mostly within two years. Obviously, these studies are highly dependent on the quality of the imaging modalities utilised. Most studies employed CT as the modality of choice, while MRI and PET was only used in selective series. Overall, the phenomenon of disappearing liver metastases seems to be a radiological rather than an actual biological occurrence, because the rates of macroscopic and microscopic residual disease are high as well as the local recurrence rates. Therefore, the disappeared metastases still require an aggressive surgical approach and standard (re)staging imaging modalities should include at least CT and MRI. PMID- 27260847 TI - Revisiting the treatment strategy for rectal cancer through the pattern of local recurrence. AB - BACKGROUND: Local recurrence after rectal cancer surgery is categorized as lymphatic spread (pelvic sidewall node (PSN)) and other types. This study aimed to investigate the risk factors associated with different patterns of local recurrence and to optimize the treatment strategy after rectal cancer surgery. METHODS: Patients with cStage I-III rectal cancer who underwent surgery at our institute were included in this study. Local recurrence was categorized as follows: (1) PSN recurrence and (2) "other" types of local recurrence. The risk factors associated with each type of recurrence (metastasis) were investigated. RESULTS: A total of 212 patients with mid/low rectal cancer were included in this study (cStage I: 66; cStage II/III: 146). Additional treatment was employed in selected patients with high-risk features (n = 45; pelvic sidewall dissection: 18; preoperative chemo (radio)therapy: 37). Potential lateral node metastasis was significantly associated with PSN enlargement on imaging findings (no/yes, odds ratio (OR): 9.1; p = 0.007). The "other" local recurrence type was significantly associated with 3 different factors as follows: clinical circumferential resection margin (no/yes; OR: 18.0; p = 0.001), tumor histology (well and moderately/poorly differentiated, OR: 17.3; p = 0.008), and tumor diameter (p = 0.018). Among 146 cStage II/III patients, 66 (45.2%) who did not have any of the abovementioned 4 risk factors experienced no local recurrence even when no additional treatment was employed. CONCLUSIONS: Risk factors may differ for different types of postoperative local recurrence patterns in rectal cancer. Recognizing these risk factors based on pretreatment findings can allow the optimization of treatment strategies for rectal cancer. PMID- 27260848 TI - Serial MRI scans help in assessing early response to neoadjuvant chemotherapy and tailoring breast cancer treatment. AB - BACKGROUND: Tailoring neoadjuvant chemotherapy (NAC) during breast cancer treatment is performed to improve overall tumour response, with increasing evidence to support its role. This study evaluates our breast unit's experience in MRI assessment of tumour response as an aid in tailoring NAC. MATERIALS AND METHODS: This is a retrospective study of patients treated with NAC for breast cancer between 2005 and 2009 who underwent MRI to assess tumour response. Response to NAC was monitored before NAC and after 2 and/or 4 cycles of anthracycline and cyclophosphamide (AC) chemotherapy. Taxane was substituted for AC if MRI response was deemed inadequate. Tumour response on last MRI was correlated with final pathology against different tumour subtypes and in inflammatory tumours. Strength of agreement was measured using Kappa analysis. Potential predictive factors for MRI response were assessed for significance. RESULTS: 166 tumours were assessed with serial MRI scans. MRI showed high sensitivity rate (93.1%) in predicting response to NAC particularly for tumours showing partial (PR) or complete (CR) response on pathology (p < 0.001) with fair agreement on Kappa analysis (K = 0.31). MRI seems more accurate in triple negative, HR+/HER2+ and high-grade tumours. Early identification of non responders on MRI resulted in early tailoring of NAC, with improved rates of tumour response seen in 74.2% following switching NAC. Logistic regression showed that PR or CR observed on MRI after 2 NAC cycles significantly predicted pCR (p < 0.001). CONCLUSION: Serial MRI can be used to assess patterns of tumour response to NAC. This study shows that tailoring NAC according to pattern of response can improve overall tumour response rates. PMID- 27260849 TI - Surgical margins do not affect prognosis in high grade myxofibrosarcoma. AB - INTRODUCTION: Myxofibrosarcoma (MFS) is one of the most common soft tissue sarcomas (STS) in elderly patients and it primarily affects the extremities. The aim of this retrospective analysis is to understand the natural history of MFS and whether adequate treatment influence prognosis. PATIENTS AND METHODS: We reviewed 129 adult patients with primary, localized, FNCLCC grade 3 MFS of the extremities operated at Istituto Ortopedico Rizzoli, Bologna. Sarcoma specific survival (SS), local recurrence (LR) and distant metastasis (DM) were analyzed. RESULTS: Among excised MFS (119), 106 (89.9%) had R0 margins, 13 (10.1%) R1 margins. No significant correlation between margins adequacy and tumor depth, location and size was found. Estimated SS was 73.2% at 5 years and 66.3% at 10 years, with a better SS in superficial MFS (p = 0.011). Local recurred MFS had a worse SS (p = 0.049). Local recurrence-free rate was 74.3% at 5 and 10 years. Even if not significant, a better outcome in term of LR was observed in superficial MFS and R0 margins. Distant metastasis-free survival was 75.6% at 5 years and 72.9% at 10 years, with a better outcome in superficial MFS (p = 0.012). DISCUSSION: Myxofibrosarcoma remain a debated entity with specific behavior features. Myxofibrosarcoma tends to local recur due to its infiltrative grow pattern making difficult to achieve "safe margins". To date, surgical margins as classified for other STS are not predictive of LR and patients' survival. Tumor grade and depth are still the most important prognostic factors. PMID- 27260850 TI - Newly identified bacteriolytic enzymes that target a wide range of clinical isolates of Clostridium difficile. AB - Clostridium difficile has emerged as a major cause of infectious diarrhea in hospitalized patients, with increasing mortality rate and annual healthcare costs exceeding $3 billion. Since C. difficile infections are associated with the use of antibiotics, there is an urgent need to develop treatments that can inactivate the bacterium selectively without affecting commensal microflora. Lytic enzymes from bacteria and bacteriophages show promise as highly selective and effective antimicrobial agents. These enzymes often have a modular structure, consisting of a catalytic domain and a binding domain. In the current work, using consensus catalytic domain and cell-wall binding domain sequences as probes, we analyzed in silico the genome of C. difficile, as well as phages infecting C. difficile. We identified two genes encoding cell lytic enzymes with possible activity against C. difficile. We cloned the genes in a suitable expression vector, expressed and purified the protein products, and tested enzyme activity in vitro. These newly identified enzymes were found to be active against C. difficile cells in a dose dependent manner. We achieved a more than 4-log reduction in the number of viable bacteria within 5 h of application. Moreover, we found that the enzymes were active against a wide range of C. difficile clinical isolates. We also characterized the biocatalytic mechanism by identifying the specific bonds cleaved by these enzymes within the cell wall peptidoglycan. These results suggest a new approach to combating the growing healthcare problem associated with C. difficile infections. Biotechnol. Bioeng. 2016;113: 2568-2576. (c) 2016 Wiley Periodicals, Inc. PMID- 27260851 TI - Dehydroepiandrosterone inhibits events related with the metastatic process in breast tumor cell lines. AB - Dehydroepiandrosterone (DHEA), an adrenal hormone, has a protective role against cancer. We previously shown that DHEA inhibits the proliferation and migration of cell lines derived from breast cancer; however, the role of DHEA in others events related with these effects are unknown. We hypothesized that DHEA inhibits the expression of proteins and some events related with cell migration and metastasis. We determined the migration in Boyden chambers, the invasion in matrigel, anchorage-independent growth and the formation of spheroids in 3 cell lines (MCF-7, MDA-MB-231, ZR-75-30) derived from breast cancer exposed to DHEA. The secretion of metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and several pro-inflammatory molecules in the secretome of these cells was also evaluated. DHEA inhibited the migration in transwells and the invasion in matrigel of MCF-7 and MDA-MB-231 cells. Besides, DHEA inhibited the anchorage-independent growth on agar and decreased the size of spheroids, and also reduced the secretion of IL-1alpha, IL-6, IL-8, and TNF-alpha in all cell lines. Metalloproteinase-1 (MMP-1) secretion was slightly decreased by DHEA treatment in MDA-MB-231 cells. Our results also showed that inhibition of migration and invasion induced by DHEA in breast cancer cells is correlated with the decrease of cytokine/chemokine secretion and the diminution of tumor cells growth. MCF-7 cells were the most responsive to the exposure to DHEA, whereas ZR 75-30 cells responded less to this hormone, suggesting that DHEA could be used in the treatment of breast cancer in early stages. PMID- 27260852 TI - A method for in situ monitoring of the isotope composition of tree xylem water using laser spectroscopy. AB - Field studies analyzing the stable isotope composition of xylem water are providing important information on ecosystem water relations. However, the capacity of stable isotopes to characterize the functioning of plants in their environment has not been fully explored because of methodological constraints on the extent and resolution at which samples could be collected and analysed. Here, we introduce an in situ method offering the potential to continuously monitor the stable isotope composition of tree xylem water via its vapour phase using a commercial laser-based isotope analyser and compact microporous probes installed into the xylem. Our technique enables efficient high-frequency measurement with intervals of only a few minutes per sample while eliminating the need for costly and cumbersome destructive collection of plant material and laboratory-based processing. We present field observations of xylem water hydrogen and oxygen isotope compositions obtained over several days including a labelled irrigation event and compare them against results from concurrent destructive sampling with cryogenic distillation and mass spectrometric analysis. The data demonstrate that temporal changes as well as spatial patterns of integration in xylem water isotope composition can be resolved through direct measurement. The new technique can therefore present a valuable tool to study the hydraulic architecture and water utilization of trees. PMID- 27260853 TI - Pitfall in the remote imaging of pyloric stenosis. PMID- 27260855 TI - Pharmacokinetics and tissue diffusion of ganciclovir in mice and rats. AB - BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of birth defects, mental retardation and non-genetic sensorineural hearing loss. Murine models have been developed in order to understand the pathophysiological mechanisms underlying these lesions. These models are being proposed for the validation of therapeutic protocols for clinical use. The aim of this preclinical study was to assess the pharmacokinetics of the reference antiviral molecule, ganciclovir, in order to optimize these protocols and confirm the diffusion of the molecule to the appropriate target zones. METHODS: Transplacental and intracochlear diffusion of ganciclovir was evaluated in mice and rats. Pharmacokinetics was assessed in adult mice and pups after 5 consecutive days of intraperitoneal injection of ganciclovir. The occurrence of hematological side effects of ganciclovir was evaluated in the different blood cell lineages. RESULTS: In adult rats, the intracochlear diffusion of ganciclovir was shown to achieve the same concentration as in blood. In gestating mice, transplacental diffusion was observed, with a fetal-to-maternal blood ratio of 0.5. In newborn mice, the plasma concentration profile of ganciclovir showed a peak at 2 h followed by a gradual decrease. In adult mice, the concentration peaked at 1 h, but became undetectable by 2 h after injection. Counts of white blood cells, red blood cells and platelets decreased significantly in ganciclovir treated newborn mice. CONCLUSION: Our data provide evidence for the intracochlear diffusion of the molecule, which may be relevant for the treatment of sensorineural hearing loss in congenitally-infected children. PMID- 27260854 TI - FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes. AB - Obesity and related metabolic disorders constitute one of the most pressing heath concerns worldwide. Increased adiposity is linked to autophagy upregulation in adipose tissues. However, it is unknown how autophagy is upregulated and contributes to aberrant adiposity. Here we show a FoxO1-autophagy-FSP27 axis that regulates adipogenesis and lipid droplet (LD) growth in adipocytes. Adipocyte differentiation was associated with upregulation of autophagy and fat specific protein 27 (FSP27), a key regulator of adipocyte maturation and expansion by promoting LD formation and growth. However, FoxO1 specific inhibitor AS1842856 potently suppressed autophagy, FSP27 expression, and adipocyte differentiation. In terminally differentiated adipocytes, AS1842856 significantly reduced FSP27 level and LD size, which was recapitulated by autophagy inhibitors (bafilomycin A1 and leupeptin, BL). Similarly, AS1842856 and BL dampened autophagy activity and FSP27 expression in explant cultures of white adipose tissue. To our knowledge, this is the first study addressing FoxO1 in the regulation of adipose autophagy, shedding light on the mechanism of increased autophagy and adiposity in obese individuals. Given that adipogenesis and adipocyte expansion contribute to aberrant adiposity, targeting the FoxO1-autophagy-FSP27 axis may lead to new anti-obesity options. PMID- 27260856 TI - Abacavir and cardiovascular disease: A critical look at the data. AB - Most HIV-infected subjects will receive a treatment regimen including abacavir or tenofovir. Therefore, clarifying if there is an increased risk of acute myocardial infarction (AMI) among those exposed to abacavir is of the utmost importance. Due to the low frequency of AMI in this young population (2-5 per 1000 patients/year), efforts to clarify this have been quite controversial. While some observational cohorts have found a statistically significant association, others have not. Meta-analysis of randomized clinical trials offering the highest scientific evidence found no association at all, but with a limited statistical power to definitely rule out a small effect. A channelling or selection bias has been demonstrated in cohort studies, favouring the prescription of abacavir to subjects with or at risk for chronic kidney disease, and therefore, with an intrinsic increased cardiovascular risk. The recent NA-ACCORD cohort study does not identify an increased risk for AMI associated with recent abacavir use in a fully adjusted model (HR 1.33; 95%CI:0.96, 1.88). However, it does find an association in a second analysis restricted to treatment-naive persons, with higher differences in baseline characteristics among compared arms. A critical review of the compiled available evidence is therefore mandatory, particularly in light of the first single-tablet regimen to receive approval that does contain abacavir. PMID- 27260857 TI - Male Reproductive Morphology Across Latitudinal Clines and Under Long-Term Female Sex-Ratio Bias. AB - SynopsisRecent work in evolutionary ecology has capitalized on the species specific, rapidly evolving nature of male reproductive traits, but it is unclear how the strength of sexual selection mechanisms, such as female choice and intersexual conflict, changes with ecological factors-shifts in latitude, elevation, and sex-ratio. Marginal habitats, such as those found at high elevation or latitude, might be expected to exert energetic hardships on males such that they do not invest heavily in reproductive structures. Conversely, males in these habitats may adapt to limited breeding opportunities, evolving morphologies with efficacy in antagonistic mating. Sex-ratio biases elicited by facultative parthenogenesis may also signal increasing selective pressure for reproductive organs that improve coercion ability, as males must capitalize on mating opportunities when females have alternate reproductive options. We studied the reproductive organs of males of five species of a group of polygynandrous Japanese harvestmen, collected from populations that varied in their elevation, latitude, and observed male: female ratio. Morphological data were analyzed with modern comparative methods, using a phylogenomic framework built with molecular data from double-digest restriction associated DNA sequencing. Although no features with hypothesized utility in coercive mating significantly covaried with elevational change, penis length was found to decrease with increasing latitude, supporting the existence of physiological constraints in marginal habitats. We also found males of parthenogenetic species, with primarily female-biased populations, had potentially greater precopulatory clasping ability, as compared to males of non-parthenogenetic species with more even sex-ratios. Ultimately, our findings suggest long-term sex-ratio biases are one of many factors with the potential to influence evolution of primary and secondary reproductive morphology. PMID- 27260858 TI - Do Developmental Constraints and High Integration Limit the Evolution of the Marsupial Oral Apparatus? AB - Developmental constraints can have significant influence on the magnitude and direction of evolutionary change, and many studies have demonstrated that these effects are manifested on macroevolutionary scales. Phenotypic integration, or the strong interactions among traits, has been similarly invoked as a major influence on morphological variation, and many studies have demonstrated that trait integration changes through ontogeny, in many cases decreasing with age. Here, we unify these perspectives in a case study of the ontogeny of the mammalian cranium, focusing on a comparison between marsupials and placentals. Marsupials are born at an extremely altricial state, requiring, in most cases, the use of the forelimbs to climb to the pouch, and, in all cases, an extended period of continuous suckling, during which most of their development occurs. Previous work has shown that marsupials are less disparate in adult cranial form than are placentals, particularly in the oral apparatus, and in forelimb ontogeny and adult morphology, presumably due to functional selection pressures on these two systems during early postnatal development. Using phenotypic trajectory analysis to quantify prenatal and early postnatal cranial ontogeny in 10 species of therian mammals, we demonstrate that this pattern of limited variation is also apparent in the development of the oral apparatus of marsupials, relative to placentals, but not in the skull more generally. Combined with the observation that marsupials show extremely high integration of the oral apparatus in early postnatal ontogeny, while other cranial regions show similar levels of integration to that observed in placentals, we suggest that high integration may compound the effects of the functional constraints for continuous suckling to ultimately limit the ontogenetic and adult disparity of the marsupial oral apparatus throughout their evolutionary history. PMID- 27260859 TI - Unravelling the Costs of Flight for Immune Defenses in the Migratory Monarch Butterfly. AB - Migratory animals undergo extreme physiological changes to prepare for and sustain energetically costly movements; one potential change is reduced investment in immune defenses. However, because some migrants have evolved to minimize the energetic demands of movement (for example, through the temporary atrophy of non-essential organs such as those involved in reproduction), migratory animals could potentially avoid immunosuppression during long-distance journeys. In this study, we used a tethered flight mill to examine immune consequences of experimentally induced powered flight in eastern North American monarch butterflies. These butterflies undergo an annual two-way long-distance migration each year from as far north as Canada to wintering sites in Central Mexico. We quantified immune measures as a function of categorical flight treatment (flown versus control groups) and continuous measures of flight effort (e.g., flight distance, duration, and measures of efficiency). We also examined whether relationships between flight and immune measures depended on reproductive investment by experimentally controlling whether monarchs were reproductive or in state of reproductive diapause (having atrophied reproductive organs) prior to flight. Of the three immune responses we measured, hemocyte concentration (the number of immune cells) was lower in flown monarchs relative to controls but increased with flight distance among flown monarchs; the other two immune measures showed no relationship to monarch flight. We also found that monarchs that were reproductively active were less efficient fliers, as they exerted more power during flight than monarchs in reproductive diapause. However, reproductive status did not modify relationships between flight and immune measures. Results of this study add to a growing body of work suggesting that migratory monarchs like some other animals that travel vast distances-can complete their journeys with efficient use of resources and minimal costs. PMID- 27260860 TI - Biting into the Genome to Phenome Map: Developmental Genetic Modularity of Cichlid Fish Dentitions. AB - Within vertebrates, teleost fishes provide a rich evolutionary context for studying the mechanisms of dental divergence because of the numerous axes along which their teeth have diverged phenotypically and presumably developmentally. Using both a review of teleost in situ hybridization and de novo transcriptome sequencing in a cichlid fish, we examined whether 341 gene homologs thought to play a role in developing mice teeth are expressed in the tooth-bearing jaws of teleosts. The similarities and putative differences in gene expression documented between the two most commonly used models, zebrafish and cichlids, highlight what can be learned from using a greater diversity of teleost model systems in studies of tooth development. Both types of gene expression analysis also provide substantial evidence for conservation of tooth gene expression from teleosts to mammals as well as between initial and replacement teeth. Additionally, we found that the cichlid oral and pharyngeal jaws share expression for a large percentage of genes that influence tooth development. Our transcriptome analyses also suggest sub-functionalization between gene paralogs expressed in teeth and paralogs expressed in other structures is likely a common pattern across teleost diversity. Teleost dentitions will continue to provide a potent system in which to examine the importance of both gene duplication as well as the conservation of gene expression for phenotypic diversification. PMID- 27260861 TI - Schistosomes with wings: how host phylogeny and ecology shape the global distribution of Trichobilharzia querquedulae (Schistosomatidae). AB - Migratory waterfowl play an important role in the maintenance and spread of zoonotic diseases worldwide. An example is cercarial dermatitis, caused when larval stages of schistosomes that normally develop in birds penetrate human skin. Members of the genus Trichobilharzia (Schistosomatidae), transmitted mainly by ducks, are considered to be major etiological agents of cercarial dermatitis globally. To better understand the diversity and distribution of Trichobilharzia spp., we surveyed ducks from the United States, eastern Canada, Argentina, South Africa and New Zealand. To aid in species identification of the Trichobilharzia worms recovered, regions of the Cox1, ND4 and ITS1 were sequenced. Furthermore, we provide molecular phylogenetic evidence for the cosmopolitan distribution and trans-hemispheric gene flow for one species, Trichobilharzia querquedulae, previously thought to be restricted to North America. These new samples from endemic non-migratory duck species indicate that T. querquedulae transmission occurs within each of the regions we sampled and that it is specific to the blue winged+silver teal duck clade. Prevalence within this host group is >95% across the known range of T. querquedulae, indicating that transmission is common. Genetic divergence is evenly distributed among continents, and no phylogenetic structure associated with geography was observed. The results provide strong support for the global distribution and transmission of T. querquedulae and represent, to our knowledge, the first report of a cosmopolitan schistosome confirmed by genetic data. These data are the first known to support trans hemispheric genetic exchange in a species responsible for causing cercarial dermatitis, indicating that the epidemiology of this group of poorly known zoonotic parasites is more complex than previously expected. PMID- 27260862 TI - Effects of potassium citrate or potassium chloride in patients with combined glucose intolerance: A placebo-controlled pilot study. AB - BACKGROUND: Experimental K(+) depletion reversibly inhibits insulin secretion, while chronic metabolic acidosis decreases insulin sensitivity. We aimed to investigate the effects of potassium supplementation and alkali supplementation in non-acidotic, normokalemic humans with combined glucose intolerance. STUDY DESIGN AND RESULTS: In this double-blind, placebo-controlled study in 11 subjects (7 male, 4 female, ages 47-63 years), 90meqs of oral KCl or Kcitrate per day for 2weeks each increased insulin production as measured by homeostasis model assessment Beta [KCl=86 (CI 81-91), Kcitrate=88 (82-94), placebo=78 (73-83)%, p<0.04], but only Kcitrate attenuated insulin resistance as assessed by HOMA-IR (insulin resistance, Kcitrate=2.8 (2.5-3.1), placebo=3.2 (2.9-3.5), p<0.03) and only Kcitrate increased quantitative insulin sensitivity check index (Quicki, Kcitrate=0.355 (0.305-0.405), placebo=0.320 (0.265-0.375) p<0.04). These results were confirmed by independent measurements, i.e. HOMA C-peptide and whole body insulin sensitivity index measured during oral glucose tolerance testing. Kcitrate significantly decreased systolic and diastolic 24-hour ambulatory blood pressures (-4.0 (-3 to -5) and -2.7 (-1.9 to -3.5), respectively as compared to placebo, p<0.02) while KCl was without a significant effect. CONCLUSIONS: K(+) supplementation in the absence of overt K(+) depletion improves beta-cell function in subjects with combined glucose intolerance. The insulin-sensitizing and hypotensive effect, however, depend on citrate as the accompanying anion. PMID- 27260863 TI - Hidden wholesale: The drug diffusing capacity of online drug cryptomarkets. AB - BACKGROUND: In spite of globalizing processes 'offline' retail drug markets remain localized and - in recent decades - typically 'closed', in which dealers sell primarily to known customers. We characterize drug cryptomarkets as 'anonymous open' marketplaces that allow the diffusion of drugs across locales. Where cryptomarket customers make stock-sourcing purchases for offline distribution, the cryptomarket may indirectly serve drug users who are not themselves cryptomarket customers, thereby increasing the drug diffusing capacity of these marketplaces. Our research aimed to identify wholesale activity on the first major cryptomarket, Silk Road 1. METHODS: Data were collected 13-15 September 2013. A bespoke web crawler downloaded content from the first major drug cryptomarket, Silk Road 1. This generated data on 1031 vendors and 10,927 drug listings. We estimated monthly revenues to ascertain the relative importance of wholesale priced listings. RESULTS: Wholesale-level revenue generation (sales for listings priced over USD $1000.00) accounted for about a quarter of the revenue generation on SR1 overall. Ecstasy-type drugs dominated wholesale activity on this marketplace, but we also identified substantial wholesale transactions for benzodiazepines and prescription stimulants. Less important, but still generating wholesale revenue, were cocaine, methamphetamine and heroin. Although vendors on the marketplace were located in 41 countries, wholesale activity was confined to only a quarter of these, with China, the Netherlands, Canada and Belgium prominent. CONCLUSIONS: The cryptomarket may function in part as a virtual broker, linking wholesalers with offline retail-level distributors. For drugs like ecstasy, these marketplaces may link vendors in producer countries directly with retail level suppliers. Wholesale activity on cryptomarkets may serve to increase the diffusion of new drugs - and wider range of drugs - in offline drug markets, thereby indirectly serving drug users who are not cryptomarket customers themselves. Cryptomarkets provide researchers and policy makers with a rich source of drug monitoring information. Further research should ascertain whether their virtual location may reduce the violence associated with middle market drug activity. We caution that conflict may instead manifest in other ways, including threats, fraud, and blackmail. PMID- 27260871 TI - Risk of second primary cancers after malignant mesothelioma and vice versa. AB - We aimed at investigating risk of specific second primary cancers (SPCs) after malignant mesothelioma (MM) and vice versa, which has not been reported. Among survivors of 3672 pleural MM and 895 peritoneal MM, overall 113 and 28 SPCs were recorded, respectively, while reverse analyses included overall 431 pleural and 88 peritoneal MMs after any first cancers. We found a bidirectional association of pleural MM with kidney cancer for overall [for second kidney cancer after pleural MM: standardized incidence ratios (SIRs) = 4.4, 95% confidence intervals (CIs): 2.0-8.3; for second pleural MM after kidney cancer: 2.3 (1.3-3.9)] and for <1 year follow-up [5.4 (2.0-12) and 4.9 (2.0-10), respectively, according to the 2-way analyses]. In contrast, a bidirectional association of pleural MM with unknown primary cancer was found only for follow-up >=1 year [3.9 (1.1-10) and 2.8 (1.3-5.1), respectively]. We found a bidirectional association of pleural MM with kidney cancer for overall and for <1 year follow-up, suggesting the involvement of germline BAP1 mutations and increased medical surveillance, while the bidirectional association of pleural MM with unknown primary cancer suggests shared genetic or environmental risk factors. PMID- 27260872 TI - Human metapneumovirus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: A systematic review. AB - Over the past decade, reported incidence of human metapneumovirus (hMPV) has increased owing to the use of molecular assays for diagnosis of respiratory viral infections in cancer patients. The seasonality of these infections, differences in sampling strategies across institutions, and small sample size of published studies make it difficult to appreciate the true incidence and impact of hMPV infections. In this systematic review, we summarized the published data on hMPV infections in hematopoietic cell transplant recipients and patients with hematologic malignancy, focusing on incidence, hMPV-associated lower respiratory tract infection (LRTI), mortality, prevention, and management with ribavirin and/or intravenous immunoglobulins. Although the incidence of hMPV infections and hMPV-associated LRTI in this patient population is similar to respiratory syncytial virus or parainfluenza virus and despite lack of directed antiviral therapy, the mortality rate remains low unless patients develop LRTI. In the absence of vaccine to prevent hMPV, infection control measures are recommended to reduce its burden in cancer patients. PMID- 27260873 TI - Opinions of Brazilian resuscitation instructors regarding resuscitation in the delivery room of extremely preterm newborns. AB - OBJECTIVE: To describe the opinions of pediatricians who teach resuscitation in Brazil on initiating and limiting the delivery room resuscitation of extremely preterm infants. METHOD: Cross-sectional study with electronic questionnaire (Dec/2011-Sep/2013) sent to pediatricians who are instructors of the Neonatal Resuscitation Program of the Brazilian Society of Pediatrics, containing three hypothetical clinical cases: (1) decision to start the delivery room resuscitation; (2) limitation of neonatal intensive care after delivery room resuscitation; (3) limitation of advanced resuscitation in the delivery room. For each case, it was requested that the instructor indicate the best management for each gestational age between 23 and 26 weeks. A descriptive analysis was performed. RESULTS: 560 (82%) instructors agreed to participate. Only 9% of the instructors reported the existence of written guidelines at their hospital regarding limitations of delivery room resuscitation. At 23 weeks, 50% of the instructors would initiate delivery room resuscitation procedures. At 26 weeks, 2% would decide based on birth weight and/or presence of fused eyelids. Among the participants, 38% would re-evaluate their delivery room decision and limit the care for 23-week neonates in the neonatal intensive care unit. As for advanced resuscitation, 45% and 4% of the respondents, at 23 and 26 weeks, respectively, would not apply chest compressions and/or medications. CONCLUSION: Difficulty can be observed regarding the decision to not resuscitate a preterm infant with 23 weeks of gestational age. At the same time, a small percentage of pediatricians would not resuscitate neonates of unquestionable viability at 26 weeks of gestational age in the delivery room. PMID- 27260874 TI - The role of compassion, suffering, and intrusive thoughts in dementia caregiver depression. AB - OBJECTIVES: Exposure to suffering of a relative or friend increases the risk for psychological and physical morbidity. However, little is known about the mechanisms that account for this effect. We test a theoretical model that identifies intrusive thoughts as a mediator of the relation between perceived physical and psychological suffering of the care recipient and caregiver depression. We also assess the role of compassion as a moderator of the relation between perceived suffering and intrusive thoughts. METHODS: Hispanic and African American caregivers (N = 108) of persons with dementia were assessed three times within a one-year period. Using multilevel modeling, we assessed the mediating role of intrusive thoughts in the relation between perceived physical and psychological suffering and CG depression, and we tested moderated mediation to assess the role of caregiver compassion in the relation between perceived suffering and intrusive thoughts. RESULTS: The effects of perceived physical suffering on depression were completely mediated through intrusive thoughts, and compassion moderated the relation between physical suffering and intrusive thoughts. Caregivers who had greater compassion reported more intrusive thoughts even when perceived physical suffering of the CR was low. For perceived psychological suffering, the effects of suffering on depression were partially mediated through intrusive thoughts. DISCUSSION: Understanding the role of intrusive thoughts and compassion in familial relationships provides new insights into mechanisms driving caregiver well-being and presents new opportunities for intervention. PMID- 27260875 TI - The efficacy and safety of sumatriptan intranasal powder in adults with acute migraine. AB - INTRODUCTION: There are multiple choices of agents for the acute management of migraine available. Patient-specific factors such as associated symptoms including nausea, vomiting, and gastroparesis are important considerations. Oral administration may often be the patient-preferred route of delivery because of comfort or convenience but when it is important to bypass gut absorption then either parenteral or intranasal administration may be appropriate delivery approaches. A new formulation of a low-dose sumatriptan intranasal powder administered via a novel breath-powered delivery device may be a viable option Areas covered: Our search of the available literature pertaining to the topic of intranasal sumatriptan powder yielded pharmacokinetic studies and randomized, double-blind, placebo-controlled trials (including The TARGET Study, The COMPASS study) published between 2010 and 2015. Expert commentary: A new formulation of a low-dose sumatriptan intranasal powder administered via a novel breath-powered delivery device appears to be a safe and efficacious option for the acute management of a migraine ideally suited for this situation. It appears to have superior efficacy to sumatriptan 100 mg oral tablets with superior pain freedom by 15 minutes and pain relief over the initial 30 minutes post-dose. PMID- 27260936 TI - Single-Cell RNA-Seq Steps Up to the Growth Plate. AB - Single-cell RNA sequencing (RNA-seq) technology is hitting its stride and is beginning to be widely adopted. One of the major challenges faced by this rapidly growing field lies in data analysis. Li et al. now present Sinova, a single-cell analytical platform offering temporal, spatial, and regulatory reconstruction of developmental processes. PMID- 27260937 TI - Initiation of strong prescription opioids in Australia: cohort characteristics and factors associated with the type of opioid initiated. AB - AIMS: To describe the characteristics of Australians initiating strong opioids and examine the factors associated with the type of opioid initiated. METHODS: Pharmaceutical Benefits Scheme dispensing records were extracted for a 10% sample of people who initiated a strong opioid treatment episode (buprenorphine, fentanyl, hydromorphone, morphine, oxycodone) between 29 September 2009 and 31 December 2013, as evidenced by the absence of a strong opioid dispensing for at least 90 days. The cohort was restricted to people with complete medicines ascertainment. Socio-demographic characteristics, previous dispensing histories and index opioid use were examined. Multinomial logistic regression was used to calculate adjusted relative risk ratios (aRRRs) and 95% confidence intervals (CIs) to determine the factors associated with the type of opioid medicine initiated, relative to oxycodone. RESULTS: The cohort consisted of 125 335 people: 58.3% were female and 63.7% were aged >=65 years. The most commonly initiated strong opioid was oxycodone (72.8%), usually 5 mg immediate-release tablets (76.1%). Compared to people aged 18-44 years, those >=85 years were 14.18 times as likely (95% CI 12.67-15.87) to initiate morphine than oxycodone. Compared to people without a cancer treatment history, those with a cancer treatment history were 2.34 times as likely (95% CI 2.11-2.60) to initiate morphine than oxycodone. CONCLUSIONS: The most commonly initiated strong opioid was oxycodone, usually at lower strengths. Those who initiated oxycodone were more likely to be younger with no previous cancer treatment history. As these are high-risk characteristics for potential harms, a judicious approach when initiating strong opioids for this group is necessary. PMID- 27260938 TI - Resuming anticoagulant therapy after intracerebral bleeding. AB - The clinical benefit of resuming anticoagulant treatment after an anticoagulants associated intracranial hemorrhage (ICH) is debated. No randomized trial has been conducted on this particular clinical issue. The risk of ICH recurrence from resuming anticoagulant therapy is expected to be higher after index lobar than deep ICH and in patients with not amendable risk factors for ICH. Retrospective studies have recently shown improved survival with resumption of treatment after index anticoagulants-associated ICH. Based on these evidences and on the risk for thromboembolic events without anticoagulant treatment, resumption of anticoagulation should be considered in all patients with mechanical heart valve prosthesis and in those with amendable risk factors for anticoagulants-associated ICH. Resumption with direct oral anticoagulants appears a reasonable option for non-valvular atrial fibrillation (NVAF) patients at moderate to high thromboembolic risk after deep ICH and for selected NVAF patients at high thromboembolic risk after lobar ICH. For VTE patients at high risk for recurrence, resumption of anticoagulation or insertion of vena cava filter should be tailored on the estimated risk for ICH recurrence. PMID- 27260939 TI - Where do we stand on vascular calcification? AB - Vascular disease, such as atherosclerosis and diabetic vasculopathy, is frequently complicated by vascular calcification. Previously believed to be an end-stage process of unregulated mineral precipitation, it is now well established to be a multi-faceted disease influenced by the characteristics of its vascular location, the origins of calcifying cells and numerous regulatory pathways. It reflects the fundamental plasticity of the vasculature that is gradually being revealed by progress in vascular and stem cell biology. This review provides a brief overview of where we stand in our understanding of vascular calcification, facing the challenge of translating this knowledge into viable preventive and therapeutic strategies. PMID- 27260941 TI - WITHDRAWN: World Apheresis Association Newsletter: April 1, 2016. AB - This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27260940 TI - Regulation of arterial reactivity by concurrent signaling through the E prostanoid receptor 3 and angiotensin receptor 1. AB - Prostaglandin E2 (PGE2), a cyclooxygenase metabolite that generally acts as a systemic vasodepressor, has been shown to have vasopressor effects under certain physiologic conditions. Previous studies have demonstrated that PGE2 receptor signaling modulates angiotensin II (Ang II)-induced hypertension, but the interaction of these two systems in the regulation of vascular reactivity is incompletely characterized. We hypothesized that Ang II, a principal effector of the renin-angiotensin-aldosterone system, potentiates PGE2-mediated vasoconstriction. Here we demonstrate that pre-treatment of arterial rings with 1nM Ang II potentiated PGE2-evoked constriction in a concentration dependent manner (AUC-Ang II 2.778+/-2.091, AUC+Ang II 22.830+/-8.560, ***P<0.001). Using genetic deletion models and pharmacological antagonists, we demonstrate that this potentiation effect is mediated via concurrent signaling between the angiotensin II receptor 1 (AT1) and the PGE2 E-prostanoid receptor 3 (EP3) in the mouse femoral artery. EP3 receptor-mediated vasoconstriction is shown to be dependent on extracellular calcium in combination with proline-rich tyrosine kinase 2 (Pyk2) and Rho-kinase. Thus, our findings reveal a novel mechanism through which Ang II and PGE2 regulate peripheral vascular reactivity. PMID- 27260942 TI - RepeatAnalyzer: a tool for analysing and managing short-sequence repeat data. AB - BACKGROUND: Short-sequence repeats (SSRs) occur in both prokaryotic and eukaryotic DNA, inter- and intragenically, and may be exact or inexact copies. When heterogeneous SSRs are present in a given locus, we can take advantage of the pattern of different repeats to genotype strains based on the SSRs. Cataloguing and tracking these repeats can be difficult as diverse groups of researchers are involved in the identification of the repeats. Additionally, the task is error-prone when done manually. RESULTS: We developed RepeatAnalyzer, a new software tool capable of tracking, managing, analysing and cataloguing SSRs and genotypes using Anaplasma marginale as a model species. RepeatAnalyzer's analysis capability includes novel metrics for measuring regional genetic diversity (corresponding to variety and regularity of SSR occurrence). As a part of its visualization capabilities, RepeatAnalyzer produces high quality maps of the geographic distribution of genotypes or SSRs over a region of interest. RepeatAnalyzer's repeat identification functionality was validated for all SSRs and genotypes reported in 21 publications, using 380 A. marginale isolates gathered from the five publications within that list that provided access to their isolates. The tool produced accurate genotyping results in every case. In addition, it uncovered a number of errors in the published literature: 11 cases where SSRs were misreported, 5 cases where two different SSRs had been given the same name, and 16 cases where two or more names had been given to a single SSR. The analysis and visualization functionalities of the tool are demonstrated using several examples. CONCLUSIONS: RepeatAnalyzer is a robust software tool that can be used for storing, managing, and analysing short-sequence repeats for the purpose of strain identification. The tool can be used for any set of SSRs regardless of species. When applied to A. marginale, our test case, we show that genotype lengths for a given region follow a normal distribution, while SSR frequencies follow a power-law-like distribution. Further, we find that over 90 % of repeats are 28 to 29 amino acids long, which is in agreement with conventional wisdom. Lastly, our analysis reveals that the most common edit distance is five or six, which is counter-intuitive since we expected that result to be closer to one, resulting from the simplest change from one repeat to another. PMID- 27260943 TI - HIF-1 alpha as a Key Factor in Bile Duct Ligation-Induced Liver Fibrosis in Rats. AB - BACKGROUND: Although several studies suggested hypoxia as an important microenvironmental factor contributing to inflammation and fibrosis in chronic liver diseases, the mechanism of this process is not fully understood. We considered hypoxia inducible factor (HIF-1alpha) as a key transcription factor in liver fibrosis. The aim of the study was to evaluate the mechanisms of signaling pathway during bile duct ligation (BDL)-induced liver fibrosis in rats. METHODS: BDL animal model of liver fibrosis was used in the study. Male Wistar rats were divided randomly into two experimental groups: sham group (n = 15), BDL group (n = 30). Hydroxyproline (Hyp) content as a marker of collagen accumulation in liver of rats subjected to BDL was evaluated according to the method described by Gerling B et al. Expression of signaling proteins [integrin beta1 receptor, HIF 1alpha, nuclear factor kappa B (NF-kappaB), and transforming growth factor (TGF beta)] was evaluated applying Western-immunoblot analysis. In all experiments, the mean values for six assays +/- standard deviations (SD) were calculated. The results were submitted to the statistical analysis using the Student's "t" test, accepting p < 0.05 as significant. RESULTS: Ligation of bile ducts was found to increase Hyp content in rat liver, accompanied by increase of HIF-1alpha expression during 10 weeks after BDL. The Hyp level was time dependent. There was not such a difference in control group (p < 0.001). Simultaneously expression of NF-kappaB, TGF-beta, beta1-integrin receptor was significantly elevated starting from sixth week after ligation. Activity of metalloproteinases 2 and 9 in the livers were increased 1 week after surgery and remained increased until the end of the experiment. CONCLUSIONS: The mechanism of development of liver fibrosis involves activation of Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9), upregulation of HIF-1alpha transcriptional activity and its related factors, NF-kappaB and TGF-beta. It suggests that they may represent targets for the treatment of the disease. PMID- 27260944 TI - Using alcohol intoxication goggles (Fatal Vision(r) goggles) to detect alcohol related impairment in simulated driving. AB - OBJECTIVE: Fatal vision goggles (FVGs) are image-distorting equipment used within driver education programs to simulate alcohol-related impairment. However, there is no empirical evidence comparing the behavioral effects associated with wearing FVGs to alcohol intoxication. The purpose of this study was to determine the validity of FVGs in producing alcohol-related impairment in simulated driving. METHODS: Twenty-two healthy males (age: 23 +/- 3 years, mean +/- SD) participated in a placebo-controlled crossover design study involving 4 experimental trials. In each trial, participants completed a baseline level simulated driving task followed by an experimental driving task, involving one of 4 treatments: (1) a dose of alcohol designed to elicit 0.080% breath alcohol concentration (BrAC; AB), (2) an alcohol placebo beverage (PB), (3) FVG (estimated % blood alcohol concentration [BAC] 0.070-0.100+), and (4) placebo goggles (PGs). The driving tasks included 3 separate scenarios lasting ~5 min each; these were a simple driving scenario, a complex driving scenario, and a hazard perception driving scenario. Selected lateral control parameters (standard deviation of lane position [SDLP]; total number of lane crossings [LCs]) and longitudinal control parameters (average speed; standard deviation of speed [SDSP]; distance headway; minimum distance headway) were monitored during the simple and complex driving scenarios. Latency to 2 different stimuli (choice reaction time [CRT]) was tested in the hazard perception driving scenario. Subjective ratings of mood and attitudes toward driving were also provided during each of the trials. RESULTS: Neither placebo treatment influenced simulated driving performance. Mean BrAC was 0.060 +/- 0.010% at the time of driving on the AB trial. Lateral control: In the simple driving scenario, SDLP and LC were not affected under any of the experimental treatments. However, in the complex driving scenario, significantly greater SDLP was observed on both the FVG and AB trials compared to their respective baseline drives. LC increased significantly from baseline on the AB trial only. Longitudinal control: Speed was not affected by any of the experimental treatments; however, SDSP increased significantly from baseline on the FVG trial. A significant reduction in distance headway and minimum distance headway was detected on the FVG trial compared to baseline. Hazard perception: Neither AB nor FVG trials were influential on CRT. Subjective mood ratings were significantly altered on the AB and FVG trials compared to baseline and placebo conditions. Participants reported reduced willingness and ability to drive under the active treatments (AB and FVG) than the placebo treatments (PB and PG). CONCLUSIONS: FVGs may have some utility in replicating alcohol-related impairment on specific driving performance measurements. Hence, the equipment may offer an alternative approach to researching the impact of alcohol intoxication on simulated driving performance among populations where the provision of alcohol would otherwise be unethical (e.g., prelicensed drivers). PMID- 27260945 TI - Readability, relevance and quality of the information in Spanish on the Web for patients with rheumatoid arthritis. AB - BACKGROUND: Education is a major health determinant and one of the main independent outcome predictors in rheumatoid arthritis (RA). The use of the Internet by patients has grown exponentially in the last decade. OBJECTIVE: To assess the characteristics, legibility and quality of the information available in Spanish in the Internet regarding to rheumatoid arthritis. MATERIAL AND METHODS: The search was performed in Google using the phrase rheumatoid arthritis. Information from the first 30 pages was evaluated according to a pre established format (relevance, scope, authorship, type of publication and financial objective). The quality and legibility of the pages were assessed using two validated tools, DISCERN and INFLESZ respectively. Data extraction was performed by senior medical students and evaluation was achieved by consensus. RESULTS: The Google search returned 323 hits but only 63% were considered relevant; 80% of them were information sites (71% discussed exclusively RA, 44% conventional treatment and 12% alternative therapies) and 12.5% had a primary financial interest. 60% of the sites were created by nonprofit organizations and 15% by medical associations. Web sites posted by medical institutions from the United States of America were better positioned in Spanish (Arthritis Foundation 4th position and American College of Rheumatology 10th position) than web sites posted by Spanish speaking countries. CONCLUSIONS: There is a risk of disinformation for patients with RA that use the Internet. We identified a window of opportunity for rheumatology medical institutions from Spanish-speaking countries to have a more prominent societal involvement in the education of their patients with RA. PMID- 27260946 TI - PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer. AB - The mechanism of carcinogenesis of gastric cancer (GC) is still unclear now. This study aimed to explore the correlations among PD-L1, Epstein-Barr virus (EBV) infection, lymphocyte infiltration, HER2 expression, HER2 gene status, histology, and other clinicopathological factors in GC. A total of 44 GC patients with massive lymphocyte infiltration (GC-MLI) and 93 GC patients without massive lymphocyte infiltration were involved in this study. Immunohistochemical analysis was used to test the expression levels of PD-L1 and HER2. Fluorescence in situ hybridization was used on HER2-positive cases with a score of 2+ to test the HER2 gene status. EBV-encoded RNA was used to test for EBV infection. In univariate analysis, PD-L1 expression was significantly associated with GC-MLI (P<.001), lower age (P=.019), EBV infection (P<.001), lower HER2 expression (P=.011), and diffuse/mixed type of histology (P=.022). EBV-encoded RNA-positive cases were significantly associated with GC-MLI (P<.001), lower age (P=.016), diffuse/mixed type of histology (P=.011), and lower HER2 expression (P=.032). In the multivariate logistic regression model, GC-MLI and the diffuse/mixed type histology were identified as 2 independent factors that affected PD-L1 expression (P<.001). Furthermore, PD-L1-positive cases have worse overall survival than do PD-L1-negative cases (P=.011). These results suggest that massive lymphocyte infiltration and the diffuse/mixed type histology of GC should be taken into consideration to select the appropriate patients for PD-L1 inhibitory treatment in the future. PMID- 27260947 TI - Dicer expression in estrogen receptor-positive versus triple-negative breast cancer: an antibody comparison. AB - Dicer is an RNase III enzyme responsible for cleaving double-stranded RNAs into small interfering RNAs and microRNAs, which either target messenger RNA transcripts for degradation or inhibit translation. Dicer protein levels have been examined in breast cancer with contradictory results. Our goal was to resolve whether Dicer levels differ in breast cancer versus normal breast epithelium and between estrogen receptor-alpha-positive (ER+) or estrogen receptor-alpha-negative (ER-) primary breast cancers. We compared 3 different Dicer antibodies: Abcam 4A6, Abcam ab5818, and Sigma HPA000694, using immunohistochemistry and Western blot analyses. All 3 Dicer antibodies detected higher levels of Dicer in ER+ breast cancer cell lines versus ER-, and all 3 recognized exogenous overexpressed Dicer. In clinical specimens, all 3 antibodies detected higher Dicer in ER+ breast cancers versus triple-negative breast cancer (TNBC) but had very different staining patterns by immunohistochemistry on the same tumor samples. Using the optimal antibody, ab5818, selected for its sensitivity and specificity, Dicer protein expression was significantly higher in ER+ versus TNBC clinical specimens of primary tumor (P<.0001, unpaired t test). Dicer was also significantly higher in adjacent normal breast epithelium versus TNBC (P<.0001, paired t test; n=18 pairs). Differences in antibody performance may explain contrasting results observed in the literature regarding Dicer protein in breast cancer. If Dicer becomes more clinically relevant as a prognostic indicator, further antibody optimization and standardization will be critical. PMID- 27260948 TI - Notch signalling in ventricular chamber development and cardiomyopathy. AB - The vertebrate heart is the first organ to form and function during embryogenesis. Primitive streak-derived cardiac progenitors located bilaterally move rostral to form the primitive heart tube that subsequently undergoes rightward looping, remodelling and septation to give rise to the mature four chambered heart. Tightly regulated tissue interactions orchestrate the patterning, proliferation and differentiation processes that give rise to the adult ventricles. Studies in animal models have demonstrated the crucial function of the Notch signalling pathway in ventricular development and how alterations in human NOTCH signalling may lead to disease in the form of cardiomyopathies, such as left ventricular noncompaction (LVNC). In this review, we discuss how during trabecular formation and ventricular compaction, Dll4-Notch1 signals from chamber endocardium to regulate cardiomyocyte proliferation and differentiation in a noncell autonomous fashion and how, at later stages, myocardial Jag1 and Jag2 activate Notch1 in chamber endocardium to sustain chamber patterning and compaction with simultaneous coronary vessel development mediated by Dll4-Notch1. We suggest that alterations in these molecular mechanisms underlie MIB1-related familial LVNC and favour the hypothesis that this cardiomyopathy has a congenital nature. PMID- 27260949 TI - [Prevalence of peripheral artery disease among diabetics in Parakou in 2013]. AB - We aimed to determine the prevalence of peripheral artery disease and its associated factors among diabetics. The cross-sectional study was conducted and included all diabetics admitted to the diabetic clinic at the Parakou University hospital during the period of 1st February and 31st July 2013. The diagnosis of peripheral artery disease was based on the Ankle Brachial Index (ABI)<0.9. The socio-demographics data, the data concerning the diabetes and its complications were recorded in each patient. They were 401 diabetics and 59.5 % were females. The mean age was 53.7+/-11.5 years. Among the diabetics, 168 fulfilled the criteria of PAD, the overall prevalence was 41.9 %. In total, 31.5 % were symptomatics according to Leriche and Fontaine classification. The main associated factors were the increase of age (P=0.01), the absence of activity with high income (P=0.004), the absence of physical activity (P=0.023), the duration of diabetes (P=0.007), the presence of peripheral neuropathy (P=0.003), the glycosylated hemoglobin>=7 % (P<0.001). After a multivariate analysis, only diabetes control was independently associated with arteriopathy (P=0,004). The PAD was more frequent among diabetics in Parakou. The associated factors must be taken into account in order to improve the management of the disease and to reduce the burden of the PAD. PMID- 27260950 TI - Transoral laser microsurgery for managing laryngeal stenosis after reconstructive partial laryngectomies. AB - OBJECTIVES/HYPOTHESIS: To retrospectively analyze our experience of transoral laser microsurgery (TLM) for treating postoperative laryngeal obstruction (POLO) after supracricoid and supratracheal laryngectomy (open partial horizontal laryngectomy [OPHL]) types 2 and 3, and to investigate potential relationships between patients' clinical features and their functional outcomes. STUDY DESIGN: A retrospective cohort study. METHODS: The prognostic influence of clinical and surgical parameters on functional outcomes was investigated in a univariate statistical setting in terms of decannulation rate (DR), time to tracheostomy closure (TTC), and number of laser procedures required (NLP). RESULTS: OPHL type 2 was associated with a better functional outcome than OPHL type 3 in terms of DR, TTC, and NLP (P = .03, P = .02, and P = .02, respectively). Annular and semicircumferential stenoses developed more frequently after OPHL type 3, and were particularly difficult to manage with TLM. Fixation of the residual arytenoid was a negative prognostic factor in terms of functional outcome in terms of DR, TTC, and NLP (P = .0002, P = .08, and P = .08, respectively). CONCLUSIONS: There is no standardized laser treatment for POLO; it must be tailored to individual patients. Identifying prognostic factors influencing functional outcome could help surgeons to earmark patients less likely to benefit from TLM for the treatment of POLO, and enable an adequate preoperative counseling, given the high probability of repeat postoperative TLM procedures. LEVEL OF EVIDENCE: 4 Laryngoscope, 2016 127:359-365, 2017. PMID- 27260951 TI - A biopsychosocial analysis of sexuality in adult males and their partners after severe traumatic brain injury. AB - PURPOSE: The primary aim of this study was to investigate changes in sexual function in males and their partners following severe TBI. Secondary aims of the study were to explore the relationship between selected sociodemographic, emotional/behavioural and sexual function variables. METHODS: Twenty males with a history of severe TBI and 20 healthy controls (HC) and their respective partners were recruited. Sexual life was assessed with the Sexuality Evaluation Schedule Assessment Monitoring (SESAMO). Study participant level of self-awareness was evaluated by the Awareness Questionnaire, whereas their neuropsychiatric and psychopathological statuses were assessed by the NPI, the HAM-D and STAI. RESULTS: A reduction in desire and frequency of sexual intercourse was found in all survivors and their partners. Moreover, higher levels of survivor depression correlated with lower partner harmony. Survivor feelings toward their partners gradually decreased over time, as did the ability to make decisions as a couple. The comparison with HC couples revealed that both survivors' and their partners' exaggerated the extent of disease. CONCLUSIONS: After male severe TBI, men appear to have a reduced quality of their sexual life, which may be more a result of relationship dysfunction than a sexual performance deficit related to their brain injury history. PMID- 27260952 TI - Health Information Brokers in the General Population: An Analysis of the Health Information National Trends Survey 2013-2014. AB - BACKGROUND: Health information exchanged between friends or family members can influence decision making, both for routine health questions and for serious health issues. A health information broker is a person to whom friends and family turn for advice or information on health-related topics. Characteristics and online behaviors of health information brokers have not previously been studied in a national population. OBJECTIVE: The objective of this study was to examine sociodemographic characteristics, health information seeking behaviors, and other online behaviors among health information brokers. METHODS: Data from the Health Information National Trends Survey (2013-2014; n=3142) were used to compare brokers with nonbrokers. Modified Poisson regression was used to examine the relationship between broker status and sociodemographics and online information seeking. RESULTS: Over half (54.8%) of the respondents were consulted by family or friends for advice or information on health topics (ie, they acted as health information brokers). Brokers represented 54.1% of respondents earning <$20,000 yearly and 56.5% of respondents born outside the United States. Women were more likely to be brokers (PR 1.34, 95% CI 1.23-1.47) as were those with education past high school (PR 1.42, CI 1.22-1.65). People aged >=75 were less likely to be brokers as compared to respondents aged 35-49 (PR 0.81, CI 0.67-0.99). Brokers used the Internet more frequently for a variety of online behaviors such as seeking health information, creating and sharing online content, and downloading health information onto a mobile device; and also reported greater confidence in obtaining health information online. CONCLUSIONS: More than 50% of adults who responded to this national survey, including those with low income and those born abroad, were providing health information or advice to friends and family. These individuals may prove to be effective targets for initiatives supporting patient engagement and disease management, and may also be well-positioned within their respective social networks to propagate health messages. PMID- 27260953 TI - Post-transplant monitoring of NK cell counts as a simple approach to predict the occurrence of opportunistic infection in liver transplant recipients. AB - BACKGROUND: Monitoring of peripheral blood lymphocyte subpopulation (PBLS) counts might be useful for estimating the risk of infection after liver transplantation (LT). METHODS: We prospectively measured total lymphocyte and PBLS counts at baseline and post-transplant months 1 and 6 in 92 LT recipients. PBLS were enumerated by single-platform 6-color flow cytometry technology. Areas under receiver operating characteristic (ROC) curves were used to evaluate the accuracy of different PBLS for predicting cytomegalovirus (CMV) disease and overall opportunistic infection (OI). Adjusted hazard ratios (aHRs) for both outcomes were estimated by Cox regression. RESULTS: After a median follow-up of 730.0 days, 29 patients (31.5%) developed 38 episodes of OI (including 22 episodes of CMV disease). The counts of CD3(+) , CD4(+) , and CD8(+) T cells, and CD56(+) CD16(+) natural killer (NK) cells at month 1 were significantly lower in patients subsequently developing OI. The NK cell count was the best predictive parameter (area under ROC curve for predicting CMV disease: 0.78; P-value = 0.001). Patients with an NK cell count <0.050 * 10(3) cells/MUL had higher cumulative incidences of CMV disease (P-value = 0.001) and overall OI (P-value <0.001). In the multivariate models, an NK cell count <0.050 * 10(3) cells/MUL at month 1 post transplantation remained as an independent risk factor for CMV disease (aHR: 5.54; P-value = 0.003) and overall OI (aHR: 7.56; P-value <0.001). CONCLUSION: Post-transplant kinetics of NK cell counts may be used as a simple and affordable proxy to the cell-mediated immunity status in LT recipients and to their associated risk of OI. PMID- 27260954 TI - Frontline Science: ATF3 is responsible for the inhibition of TNF-alpha release and the impaired migration of acute ethanol-exposed monocytes and macrophages. AB - Binge drinking represses host innate immunity and leads to a high risk of infection. Acute EtOH-pretreated macrophages exhibit a decreased production of proinflammatory mediators in response to LPS. ATF3 is induced and counter regulates the LPS/TLR4 inflammatory cascade. Here, we investigated the potential role of ATF3 in LPS tolerance in acute ethanol-pretreated macrophages. We found that there was an inverse correlation between ATF3 and LPS-induced TNF-alpha production in acute ethanol-pretreated murine monocytes and macrophages. The knockdown of ATF3 attenuated the inhibitory effects of acute ethanol treatment on LPS-induced TNF-alpha production. Furthermore, ChIP assays and co-IP demonstrated that ATF3, together with HDAC1, negatively modulated the transcription of TNF alpha. In binge-drinking mice challenged with LPS, an up-regulation of ATF3 and HDAC1 and a concomitant decrease in TNF-alpha were observed. Given that HDAC1 was concomitantly induced in acute ethanol-exposed monocytes and macrophages, we used the HDACi TSA or silenced HDAC1 to explore the role of HDAC1 in acute ethanol treated macrophages. Our results revealed that TSA treatment and HDAC1 knockdown prevented acute ethanol-induced ATF3 expression and the inhibition of TNF-alpha transcription. These data indicated a dual role for HDAC1 in acute ethanol induced LPS tolerance. Furthermore, we showed that the induction of ATF3 led to the impaired migration of BM monocytes and macrophages. Overall, we present a novel role for ATF3 in the inhibition of LPS-induced TNF-alpha and in the impairment of monocyte and macrophage migration. PMID- 27260955 TI - Milk fat globule epidermal growth factor-8 limits tissue damage through inflammasome modulation during renal injury. AB - Mediators released by apoptotic renal resident cells play a crucial role in modification of the inflammatory microenvironment. We have demonstrated that milk fat globule epidermal growth factor 8 (MFG-E8) is released by apoptotic cells, which results in reduced proinflammatory cytokine production by macrophages. The present study was designed to study the role of MFG-E8 on the modulation of tissue damage and macrophage phenotype in a renal inflammatory model, unilateral ureteral obstruction (UUO). C57BL/6 WT or MFG-E8 KO mice underwent ureteral ligation for 3, 7, and 14 d to evaluate renal injury. MFG-E8 (30 ug/kg) or vehicle was also administered i.p. MFG-E8 administration reduced kidney damage and fibrosis compared with control, whereas its absence in MFG-E8 KO mice was associated with more severe disease. Moreover, MFG-E8 administration was associated with decreased inflammasome activation in the kidney. Furthermore, adoptive transfer of MFG-E8-stimulated macrophages reduced activation of inflammasome and tissue damage. In all cases, both the systemic administration of MFG-E8 and MFG-E8-treated macrophages promoted accumulation of anti-inflammatory CD206+ macrophages. We propose that the protective role of MFG-E8 is mediated through anti-inflammatory macrophage reprogramming which results in decreased inflammasome activation, preventing severe tissue damage. These data provide valuable insight for identification of MFG-E8 as a novel target in modulation of inflammatory diseases. PMID- 27260956 TI - [Medicine 2.0]. PMID- 27260958 TI - Blue is the new black. PMID- 27260957 TI - Outcomes of ring versus suture annuloplasty for tricuspid valve repair in patients undergoing mitral valve surgery. AB - OBJECTIVE: There is controversy regarding the comparative effectiveness of methods of tricuspid valve (TV) repair-prosthetic ring versus suture annuloplasty in patients undergoing operation for primary mitral valve (MV) disease. In this study, we analyzed factors associated with patient survival and recurrent tricuspid regurgitation (TR) following TV repair and focused on results stratified by method of tricuspid valve repair. METHODS: We reviewed patients who underwent TV repair with suture (De Vega) or flexible ring annuloplasties at the time of MV surgery from 1995 to 2010. Patients with prior cardiac or concomitant aortic valve operations were excluded. Propensity matching was performed to account for potential differences in baseline characteristics between the groups. Primary outcomes were long-term mortality and postoperative TR grade. RESULTS: In the overall study, there were 415 patients with median age 72 years (range, 63-78 years), from which 148 matched pairs were identified by propensity score analysis. In the overall cohort, patients in the ring annuloplasty group more often had preoperative transvenous pacemakers (P = .05), lower ejection fractions (P = .028), and more recent years of operation (P < .001). For patients who had De Vega suture annuloplasty, long-term mortality was not different from that of patients who had ring annuloplasty (hazard ratio, 0.93; 95% confidence interval, 0.67-1.30). Older age, preoperative diabetes, and preoperative right ventricular dysfunction were predictors for long-term mortality. Durability of the annuloplasty methods was similar with no significant difference in trend of recurrent TR grades over follow-up (P = .807). Etiology of mitral regurgitation was not associated with recurrent TR during follow-up (P = .857). CONCLUSIONS: Late survival and TV durability following concomitant TV repair during MV surgery did not differ with respect to TV repair technique. In this series of patients with repaired tricuspid valves, etiology of MV disease did not influence postoperative changes in TR. PMID- 27260959 TI - Y-en-Y airway stents: A complex solution for a complex problem. PMID- 27260960 TI - Resect them all. PMID- 27260961 TI - Profiling of the toxicity mechanisms of coated and uncoated silver nanoparticles to yeast Saccharomyces cerevisiae BY4741 using a set of its 9 single-gene deletion mutants defective in oxidative stress response, cell wall or membrane integrity and endocytosis. AB - The widespread use of nanosilver in various antibacterial, antifungal, and antiviral products warrants the studies of the toxicity pathways of nanosilver enabled materials toward microbes and viruses. We profiled the toxicity mechanisms of uncoated, casein-coated, and polyvinylpyrrolidone-coated silver nanoparticles (AgNPs) using Saccharomyces cerevisiae wild-type (wt) and its 9 single-gene deletion mutants defective in oxidative stress (OS) defense, cell wall/membrane integrity, and endocytosis. The 48-h growth inhibition assay in organic-rich growth medium and 24-h cell viability assay in deionized (DI) water were applied whereas AgNO3, H2O2, and SDS served as positive controls. Both coated AgNPs (primary size 8-12nm) were significantly more toxic than the uncoated (~85nm) AgNPs. All studied AgNPs were ~30 times more toxic if exposed to yeast cells in DI water than in the rich growth medium: the IC50 based on nominal concentration of AgNPs in the growth inhibition test ranged from 77 to 576mg Ag/L and in the cell viability test from 2.7 to 18.7mg Ag/L, respectively. Confocal microscopy showed that wt but not endocytosis mutant (end3Delta) internalized AgNPs. Comparison of toxicity patterns of wt and mutant strains defective in OS defense and membrane integrity revealed that the toxicity of the studied AgNPs to S. cerevisiae was not caused by the OS or cell wall/membrane permeabilization. PMID- 27260962 TI - Clinical and immunological study of mucous membrane pemphigoid in a cohort of Indian patients. PMID- 27260963 TI - Microglial number is related to the number of tyrosine hydroxylase neurons in SHR and normotensive rats. AB - Microglia are ubiquitously distributed throughout the central nervous system (CNS) and play a critical role in the maintenance of neuronal homeostasis. Recent advances have shown that microglia, never resting cells of the CNS, continuously monitor and influence neuronal/synaptic activity levels, by communicating with neurons with the aid of their dynamic processes. The brainstem contains many catecholaminergic nuclei that are key to many aspects of brain function. This includes C1 neurons of the ventrolateral medulla that are thought to play a critical role in control of the circulation. Despite the role of catecholaminergic brainstem neurons in normal physiology, the presence of microglia that surrounds them is poorly understood. Here, we investigate the spatial distribution and morphology of microglia in catecholaminergic nuclei of the brainstem in 3 strains of rat: Sprague-Dawley (SD), Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Our data reveal that microglia are heterogeneously distributed within and across different strains of rats. Interestingly, intra-strain comparison of tyrosine hydroxylase-immunoreactive (TH ir) neuronal and microglial number reveals that microglial number varies with the TH-ir neuronal number in the brainstem. Even though microglial spatial distribution varies across brainstem nuclei, microglial morphology (% area covered, number of end point processes and branch length) does not differ significantly. This work provides the first evidence that even though microglia, in their surveilling state, do not vary appreciably in their morphology across brainstem areas, they do have a heterogeneous pattern of distribution that may be influenced by their local environment. PMID- 27260965 TI - Questioning risk-based fire and life safety education age priorities. PMID- 27260964 TI - The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder. AB - beta3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the beta3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by beta1/beta2-adrenoceptor mechanisms. No evidence was obtained for any beta3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of beta3 adrenergic agonists remains unknown. PMID- 27260966 TI - Therapeutic innovations in endocrine diseases - Part 2: Modified-release glucocorticoid compounds: What good do they provide to the adrenal insufficient patient? AB - Intensive researches on modified-release hydrocortisone compounds developed in the last decade have paved the way for obtaining near-physiological glucocorticoid replacement in the adrenal insufficient patient. The dual-release Duocort (Plenadren) allows a unique morning intake and closely mimics the circadian rhythm of cortisol secretion, except for the progressive nocturnal increase and the morning cortisol peak observed in healthy subjects. Duocort treatment during a 6-month period was associated with favorable changes in weight, blood pressure and glycemic control in patients with diabetes mellitus. Chronocort, a multiparticulate formulation with sustained-release properties replaces endogenous cortisol in a near-physiologic manner and fully restores the end of night cortisol peak. A twice-daily Chronocort regimen was effective in controlling androgen excess in adults with CAH. Recently, the new multiparticulate formulation Infacort was designed for the treatment of adrenal insufficiency during infancy. Long term effectiveness and safety studies are needed until these promising hydrocortisone formulations become routine therapeutic tools in adrenal insufficiency. PMID- 27260967 TI - Recombinant expression, refolding, purification and characterization of Pseudomonas aeruginosa protease IV in Escherichia coli. AB - Several protease IV enzymes are widely used in proteomic research. Specifically, protease IV from Pseudomonas aeruginosa has lysyl endopeptidase activity. Here, we report the recombinant expression, refolding, activation, and purification of this protease in Escherichia coli. Proteolytic instability of the activated intermediate, a major obstacle for efficient production, is controlled through ammonium sulfate precipitation. The purified protease IV exhibits superior lysyl endopeptidase activity compared to a commercial product. PMID- 27260968 TI - Energy transfer between fusion biliproteins co-expressed with phycobiliprotein in Escherichia coli. AB - In cyanobacteria, phycobiliproteins (PBS) show excellent energy transfer among the chromophores absorbing over most of the visible. The energy transfers are used to study phycobilisome assembly and bioimaging. Using All4261GAF2(C81L) as energy donor, ApcE(1-240/Delta87-130) as energy acceptor, we co-expressed fusion protein ApcE(1-240/Delta87-130)::All4261GAF2(C81L) with phycobiliprotein in Escherichia Coli and studied the energy transfer between two protein domains. With N-terminal His6 tag, ApcE(1-240/Delta87-130)::All4261GAF2(C81L) cannot be purified by nickel-affinity column. We added six histidines in the C-terminal of ApcE(1-240/Delta87-130)::All4261GAF2(C81L) and co-expressed it with phycobiliprotein. ApcE(1-240/Delta87-130)::PCB-All4261GAF2(C81L)His6 was purified successfully and only singly chromophorylated at All4261GAF2(C81L)His6 domain. The singly chromophorylate ApcE(1-240/Delta87-130)::PCB-All4261GAF2(C81L)His6 was incubated with fresh PCB and the doubly chromophorylated PCB-ApcE(1-240/Delta87 130)::PCB-All4261GAF2(C81L)His6 was obtained. The double chromophored fusion protein absorbed light in the range of 615-660 nm, and fluoresced only at 668 nm. Photochemistry analysis showed that excitation energy transfer from the short wavelength absorbing at All4261GAF2(C81L) domain was achieved successfully to the long-wavelength absorbing at the ApcE(1-240/Delta87-130) domain. PMID- 27260969 TI - Production of soluble truncated spike protein of porcine epidemic diarrhea virus from inclusion bodies of Escherichia coli through refolding. AB - The emergence of highly pathogenic variant porcine epidemic diarrhea virus (PEDV) strains, from 2013 to 2014, in North American and Asian countries have greatly threatened global swine industry. Therefore, development of effective vaccines against PEDV variant strains is urgently needed. Recently, it has been reported that the N-terminal domain (NTD) of S1 domain of PEDV spike protein is responsible for binding to the 5-N-acetylneuraminic acid (Neu5Ac), a possible sugar co-receptor. Therefore, the NTD of S1 domain could be an attractive target for the development of subunit vaccines. In this study, the NTD spanning amino acid residues 25-229 (S25-229) of S1 domain of PEDV variant strain was expressed in Escherichia coli BL21 (DE3) in the form of inclusion bodies (IBs). S25-229 IBs were solubilized in 20 mM sodium acetate (pH 4.5) buffer containing 8 M urea and 1 mM dithiothreitol with 95% yield. Solubilized S25-229 IBs were refolded by 10 fold flash dilution and purified by one-step cation exchange chromatography with >95% purity and 20% yield. The CD spectrum of S25-229 showed the characteristic pattern of alpha helical structure. In an indirect ELISA, purified S25-229 showed strong reactivity with mouse anti-PEDV sera. In addition, immunization of mice with 20 MUg of purified S25-229 elicited highly potent serum IgG titers. Finally, mouse antisera against S25-229 showed immune reactivity with native PEDV S protein in an immunofluorescence assay. These results suggest that purified S25 229 may have potential to be used as a subunit vaccine against PEDV variant strains. PMID- 27260970 TI - Quality of death among hospice decedents: Proxy observations from a survey of community-dwelling adults in the contiguous United States. AB - This study examines hospice service experience and quality of death. A survey of 123 community-dwelling adults in the United States found that physical comfort, pain-free, and spiritual peace were more important to respondents reporting a personal experience with hospice. A "good death" was associated with older patients who died at home, and respondent satisfaction with hospice service. A "good death" was mapped as 29 nodes and 79 links using semantic network analysis. Three subjects (patient, family, hospice), three timeframes (end-of-life, moment of dying, death), and four central causes (home, peaceful, pain-free, and expected) were identified. PMID- 27260971 TI - Intraoperative spinal digital subtraction angiography: indications, technique, safety, and clinical impact. AB - BACKGROUND: Cerebral intraoperative DSA (IODSA) is a well-described, routinely performed procedure that allows the effectiveness of cerebrovascular interventions to be evaluated in the operating room. Spinal IODSA, on the other hand, is infrequently obtained and has received less attention. OBJECTIVE: To discuss the indications, technique, safety, and clinical impact of spinal IODSA. MATERIALS AND METHODS: Twenty-three patients underwent 45 thoracic and/or lumbar spinal IODSA between 2005 and 2016, either immediately before surgery for lesion localization or after the intervention to evaluate its effectiveness. Indications included 21 vascular malformations and 2 diaphragmatic crus compression syndromes. A long femoral arterial sheath with its hub positioned on the lateral surface of the thigh was used to allow catheter manipulations in the prone position. RESULTS: All targeted intersegmental arteries (ISAs) were successfully catheterized. The course of surgery was changed in 6 instances (26.1%). In 4 cases of epidural or perimedullary arteriovenous fistulae (AVFs), a residual lesion required additional intervention. In one case of epidural AVF, initial IODSA revealed spontaneous resolution of the lesion, preventing unnecessary surgery. Finally, angiography performed in a case of diaphragmatic crus syndrome showed thrombosis of the ISA and non-visualization of the artery of Adamkiewicz. Recanalization was obtained by IA thrombolysis, with excellent clinical outcome. No intraprocedural or postprocedural complication was noted. CONCLUSIONS: Spinal IODSA is a safe technique that offers an immediate assessment of the effectiveness of a spinovascular surgical procedure, notably epidural and perimedullary AVFs. Spinal IODSA was technically successful in all cases, influencing the surgical strategy in 6 of 23 patients, including one patient who benefited from intraoperative endovascular therapy. PMID- 27260972 TI - Aneurysm outflow angle at MRA as discriminant for accurate diagnosis and differentiation between small sidewall cerebral aneurysms and infundibula. AB - OBJECTIVE: To evaluate whether the aneurysm outflow angle (OA) at MR angiography (MRA) might serve as discriminant for accurate diagnosis of, and differentiation between, small sidewall cerebral aneurysms (SCAs) and infundibula. METHODS: Between June 2007 and July 2015, 426 consecutive patients with SCAs completed both an MRA and DSA examination. Of these, 156 patients with small SCAs and 52 patients with infundibula were included in this study. A patient with an OA >=90 degrees was defined as having a SCA, while those with OA <90 degrees were defined as having an infundibulum. RESULTS: DSA identified 172 SCAs in 156 patients and 55 infundibula in 52 patients. The average OA on MRA was 102.96 degrees +/-13.36 degrees (range 60 degrees -151 degrees ) in 172 SCAs of 156 patients. An OA of >=90 degrees was seen for 159 (92.4%) small SCAs in 147 patients, while an OA of <90 degrees was observed for 13 SCAs. The average OA on MRA was 69.05 degrees +/-14.26 degrees (range 35-107 degrees ) in 55 infundibula of 52 patients. An OA of >=90 degrees was seen in one patient with one infundibulum; while an OA of <90 degrees was observed for 54 infundibula (98.2%) in 51 patients. The average OA in SCAs (n=172) was greater than the average OA in infundibula (n=55; 102.96 degrees vs 69.05 degrees , p<0.001). CONCLUSIONS: The OA at MRA could serve as discriminant for accurate diagnosis of, and differentiation between, small SCAs and infundibula. PMID- 27260973 TI - Clinical outcomes following corticosteroid administration in patients with delayed diagnosis of spinal arteriovenous fistulas. AB - BACKGROUND AND PURPOSE: There have been several previously reported cases of acute progression of myelopathic symptoms in patients with spinal arteriovenous fistula (SAVF) treated with intravenous methylprednisolone. This usually occurs during or immediately following steroid administration. We examined a small case series of patients with SAVF treated with epidural, oral, or intravenous steroids to determine the association between steroid administration and clinical outcomes in these patients. METHODS: Following Institutional Review Board approval, we conducted a retrospective review of patients with angiographically-confirmed SAVF who received intravenous, oral, or epidural corticosteroids for treatment of their symptoms. We studied patient-reported motor and sensory function following steroid administration using both the modified Rankin Scale and the Aminoff Motor Disability Scale. RESULTS: Twenty-one patients with SAVF were included in this study. Thirteen patients (61.9%) had intravenous methylprednisolone administered, four patients (19.0%) had epidural steroid injections, and six patients (28.6%) had oral prednisone. Among patients who received intravenous methylprednisolone, seven (53.8%) reported acute worsening of symptoms during or immediately following steroid administration. Among the patients receiving epidural steroids, none reported worsening and one patient reported short-term relief. Among the patients receiving oral steroids, one reported acute worsening of symptoms. Worsened deficits did not consistently resolve after steroid discontinuation. CONCLUSIONS: Our study suggests that intravenous methylprednisolone can cause immediate worsening of motor and sensory symptoms when administered to patients with SAVF. Steroid administration should be avoided in patients with a myelopathy secondary to an untreated SAVF because neurological worsening may not be fully reversible. PMID- 27260974 TI - The role of antenatal corticosteroids in twin pregnancies complicated by preterm birth. AB - BACKGROUND: Data regarding the effects of antenatal corticosteroids in twin pregnancies are limited because of the insufficient number of women with twins enrolled in randomized controlled trials on antenatal corticosteroids. Furthermore, the interpretation of available data is limited by the fact that the interval from the administration of antenatal corticosteroids to delivery is greater than 7 days in a large proportion of twins, a factor that has been shown to affect the efficacy of antenatal corticosteroids and has not been controlled for in previous studies. OBJECTIVE: The objective of the study was to compare neonatal mortality and morbidity in preterm twins receiving a complete course of antenatal corticosteroids 1-7 days before birth to those who did not receive antenatal corticosteroids and to compare these outcome effects with those observed in singletons. STUDY DESIGN: We performed a retrospective cohort study using data collected on singleton and twin neonates born between 24(0/7) and 33(6/7) weeks' gestational age and were admitted to tertiary neonatal units in Canada between 2010 and 2014. A comparison of neonatal outcomes between twin neonates who received a complete course of antenatal corticosteroids 1-7 days before birth (n = 1758) and those who did not receive antenatal corticosteroids (n = 758) and between singleton neonates who received a complete course of antenatal corticosteroids 1-7 days before birth (n = 4638) and those did not receive antenatal corticosteroids (n = 2312) was conducted after adjusting for gestational age, sex, hypertension, outborn status, small for gestational age, parity, and cesarean birth. Adjusted odds ratios and 95% confidence intervals for various neonatal outcomes were calculated. RESULTS: Administration of a complete course of antenatal corticosteroids within 1-7 days before birth in both twins and singletons was associated with similar reduced odds of neonatal death (for twins adjusted odds ratio 0.42 [95% confidence interval, 0.24-0.76] and for singletons adjusted odds ratios, 0.38 [95% confidence interval, 0.28-0.50]; P = .7 for comparison of twins vs singletons), mechanical ventilation (for twins adjusted odds ratio, 0.47 [95% confidence interval, 0.35-0.63] and for singletons adjusted odds ratio, 0.47 [95% confidence interval, 0.41-0.55]; P = .9), respiratory distress syndrome (for twins adjusted odds ratio, 0.53 [95% confidence interval, 0.40-0.69], and for singletons adjusted odds ratio, 0.54 [95% confidence interval, 0.47-0.62]; P = .9) and severe neurological injury (for twins adjusted odds ratio, 0.50 [95% confidence interval, 0.30-0.83] and for singletons adjusted odds ratio, 0.45 [95% confidence interval, 0.34-0.59]; P = .7). Administration of a complete course of antenatal corticosteroids was not associated with a reduced odds of bronchopulmonary dysplasia, severe retinopathy of prematurity, or necrotizing enterocolitis in both twins and singletons. CONCLUSION: Administration of a complete course of antenatal corticosteroids 1-7 days before birth in twin pregnancies is associated with a clinically significant decrease in neonatal mortality, short-term respiratory morbidity, and severe neurological injury that is similar in magnitude to that observed among singletons. PMID- 27260985 TI - System dynamics-based evaluation of interventions to promote appropriate waste disposal behaviors in low-income urban areas: A Baltimore case study. AB - Inappropriate waste disposal is a serious issue in many urban neighborhoods, exacerbating environmental, rodent, and public health problems. Governments all over the world have been developing interventions to reduce inappropriate waste disposal. A system dynamics model is proposed to quantify the impacts of interventions on residential waste related behavior. In contrast to other models of municipal solid waste management, the structure of our model is based on sociological and economic studies on how incentives and social norms interactively affect waste disposal behavior, and its parameterization is informed by field work. A case study of low-income urban neighborhoods in Baltimore, MD, USA is presented. The simulation results show the effects of individual interventions, and also identify positive interactions among some potential interventions, especially information and incentive-based policies, as well as their limitations. The model can help policy analysts identify the most promising intervention packages, and then field test those few, rather than having to pilot test all combinations. Sensitivity analyses demonstrate large uncertainties about behavioral responses to some interventions, showing where information from survey research and social experiments would improve policy making. PMID- 27260975 TI - PGRMC1 participates in late events of bovine granulosa cells mitosis and oocyte meiosis. AB - Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in both oocyte and ovarian somatic cells, where it is found in multiple cellular sub compartments including the mitotic spindle apparatus. PGRMC1 localization in the maturing bovine oocytes mirrors its localization in mitotic cells, suggesting a possible common action in mitosis and meiosis. To test the hypothesis that altering PGRMC1 activity leads to similar defects in mitosis and meiosis, PGRMC1 function was perturbed in cultured bovine granulosa cells (bGC) and maturing oocytes and the effect on mitotic and meiotic progression assessed. RNA interference-mediated PGRMC1 silencing in bGC significantly reduced cell proliferation, with a concomitant increase in the percentage of cells arrested at G2/M phase, which is consistent with an arrested or prolonged M-phase. This observation was confirmed by time-lapse imaging that revealed defects in late karyokinesis. In agreement with a role during late mitotic events, a direct interaction between PGRMC1 and Aurora Kinase B (AURKB) was observed in the central spindle at of dividing cells. Similarly, treatment with the PGRMC1 inhibitor AG205 or PGRMC1 silencing in the oocyte impaired completion of meiosis I. Specifically the ability of the oocyte to extrude the first polar body was significantly impaired while meiotic figures aberration and chromatin scattering within the ooplasm increased. Finally, analysis of PGRMC1 and AURKB localization in AG205-treated oocytes confirmed an altered localization of both proteins when meiotic errors occur. The present findings demonstrate that PGRMC1 participates in late events of both mammalian mitosis and oocyte meiosis, consistent with PGRMC1's localization at the mid-zone and mid-body of the mitotic and meiotic spindle. PMID- 27260986 TI - Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM). AB - The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5 10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from rubrospinal tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by rubrospinal tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions. PMID- 27260987 TI - Neural activity during self-referential working memory and the underlying role of the amygdala in social anxiety disorder. AB - Self-referential processing, theory of mind, and working memory are distorted in social anxiety disorder (SAD). This study aimed to investigate characteristics of altered self-referential working memory processing and resting-state functional connectivity in patients with SAD. Twenty patients and 20 healthy controls underwent functional magnetic resonance imaging at resting-state and while performing a working memory task containing faces with self-referential positive or negative comments and three memory phases (encoding, maintenance, and retrieval). Task-related results were compared between groups and tested for correlations. Resting-state connectivity between amygdala subregions and regions showing a task-related difference was also compared between groups. Patients compared to controls showed augmented memory for the negative comments, hyperactivation of the dorsomedial prefrontal cortex and temporo-parietal junction during encoding, and hypoactivation of the dorsolateral prefrontal cortex and insula during retrieval. At resting-state, increased connectivity of amygdala subregions with multiple task-related regions was found in patients. These findings suggest that the encoding process in SAD is accompanied by altered involvement of self-referential processing and theory of mind, whereas the retrieval process reflects impaired cognitive control. These memory-related processing may be affected by predisposing resting-state hyperconnectivity with the amygdala, and may underlie a hypersensitivity to negative comments and post event reflection in SAD. PMID- 27260988 TI - Up-regulation of stem cell markers by P21-activated kinase 1 contributes to 5 fluorouracil resistance of colorectal cancer. AB - Cancer stem cells (CSC) are tumorigenic and resistant to chemotherapy. In colorectal cancer (CRC), CSCs have been identified by the expression of specific markers, including CD44, Bmi1 and Nanog. Although p21-activated kinase 1 (PAK1), acting downstream of Ras, stimulates Wnt/beta-catenin signaling and is known to play an important role in CRC development and progression, the role of PAK1 in the expression of CSC markers has not previously been investigated. The effect of PAK1 over-expression, knockdown or inhibition on the expression or alteration (in the case of CD44) of CSC markers in human CRC cell lines was measured by immunofluorescence and Western blotting. The effect of PAK1 modulation on tumorigenesis, and on resistance to treatment with 5-fluorouracil (5-FU), was measured by sphere formation in vitro and by growth of xenografted tumors in vivo. The results show that PAK1 activity correlated with the expression of CSC markers and the CD44 isoform profile, and with tumor growth both in vitro and in vivo. Furthermore PAK overexpression partially overcame the inhibition of CRC growth by 5-FU, and PAK inhibition was synergistic with 5-FU treatment. Our findings lay the foundation for a combination therapy in which PAK1 inhibitors targeting CSCs may be combined with conventional 5-FU-based chemotherapy for the treatment of CRC. PMID- 27260989 TI - Rapid and reliable identification of waterborne Legionella species by MALDI-TOF mass spectrometry. AB - Detection and enumeration of Legionella bacteria in drinking water is regulated in Germany by ISO 11731-2. The mandatory method for species identification employs parallel subculturing of suspicious colonies on selective media requiring the handling of a large number of cultivation plates. After changes to the drinking water quality regulation in Germany in 2012 the demand for Legionella contamination testing increased drastically. A more reliable, faster and less laborious method for species identification is therefore desirable. Matrix assisted laser desorption ionization followed by time of flight detection mass spectrometry (MALDI-TOF MS) promises an accelerated identification of bacteria with high reliability and reduced expenditure. Our study shows that MS-based species identification results are in full concordance with cultural and biochemical detection and differentiation and that valuable additional information can be gained, even though the ISO regulation demands an extended incubation period for primary bacterial cultures that is actually in contrast to the prerequisites of the MALDI Biotyper system. In addition, the established identification algorithm is very economical and improves time-to-result. Based on our findings, the amendment of MALID-TOF MS identification to ISO11731-2 as an alternative identification method should be taken into consideration. PMID- 27260990 TI - The effect of direct and counter-current flow-through delignification on enzymatic hydrolysis of wheat straw, and flow limits due to compressibility. AB - This article compares the processes for wheat straw lignocellulose fractionation by percolation, counter-current progressing batch percolation and batch reaction at low NaOH-loadings (3-6% of DM). The flow-through processes were found to improve delignification and subsequent enzymatic saccharification, reduce NaOH consumption and allow reduction of thermal severity, whereas hemicellulose dissolution was unaffected. However, contrary to previous expectations, a counter current process did not provide additional benefits to regular percolation. The compressibility and flow properties of a straw bed were determined and used for simulation of the packing density profile and dynamic pressure in an industrial scale column. After dissolution of 30% of the straw DM by delignification, a pressure drop above 100 kPa m-1 led to clogging of the flow due to compaction of straw. Accordingly, the maximum applicable feed pressure and volumetric straw throughput was determined as a function of column height, indicating that a 10 m column can be operated at a maximum feed pressure of 530 kPa, corresponding to an operation time of 50 min and a throughput of 163 kg m-3 h-1 . Biotechnol. Bioeng. 2016;113: 2605-2613. (c) 2016 Wiley Periodicals, Inc. PMID- 27260991 TI - Editorial Comment. PMID- 27260992 TI - Reply by Authors. PMID- 27260993 TI - Editorial Comment. PMID- 27260994 TI - Conversion to hemiarthroplasty as a salvage procedure for failed reverse shoulder arthroplasty. AB - BACKGROUND: Optimal treatment of a failed reverse shoulder arthroplasty (RSA) is unclear. In the case of poor glenoid bone stock, retaining a RSA may be infeasible. We report our experience with conversions to hemiarthroplasty. METHODS: Within 7 years, 16 patients underwent conversion to hemiarthroplasty after failed RSA. All patients had insufficient bone stock for reimplantation of another RSA. Standard radiographs and Constant, Shoulder Pain and Disability Index, and the 11-item version of the Disabilities of the Arm, Shoulder and Hand scores were assessed preoperatively and up to a minimum of 24 months after surgery. Postoperative superior migration and complications were also documented. RESULTS: Glenoid loosening was the primary reason for RSA failure in 11 patients. Three required revision surgery because of infection. Postoperative functional outcome was generally poor at the latest follow-up, with mean Constant, Shoulder Pain and Disability Index, and 11-item version of the Disabilities of the Arm, Shoulder and Hand scores of 25, 37, and 63 points, respectively. Baseline pain also did not improve. Medialization progressed beyond the coracoid in 6 patients, and complete anterosuperior escape was reported in 3 patients. Three postoperative complications were recorded by the final follow-up, including 2 periprosthetic humeral fractures treated conservatively and 1 patient with painful humeral component medialization leading to resection arthroplasty. CONCLUSION: With excessive bone stock loss, hemiarthroplasty remains an option, despite the associated risks of uncertain pain relief and poor functional outcome. This technique offers a lower likelihood of undertaking further surgical interventions within the short-term to midterm postoperative period. Nevertheless, resection arthroplasty may still be considered another valuable solution. PMID- 27260995 TI - Intra-articular lesions and their relation to arthroscopic stabilization failure in young patients with first-time and recurrent shoulder dislocations. AB - BACKGROUND: This study aimed to compare the frequency of intra-articular lesions between young patients with first-time shoulder dislocations and those with recurrent shoulder dislocations and to assess the correlation between intra articular lesions and failure of arthroscopic stabilization. METHODS: The study enrolled 33 patients who underwent arthroscopic Bankart repair after first-time shoulder dislocation before the age of 30 years. There were 89 age-matched patients who were treated arthroscopically for recurrent dislocation included as a control group. RESULTS: Among intra-articular pathologic findings, anterior glenoid erosion (P = .043) and anterior labral periosteal sleeve avulsion lesions (P = .048) were found more frequently in the recurrent dislocation group. There was no statistically significant difference between the 2 groups in American Shoulder and Elbow Surgeons (P = .675) and Rowe (P = .132) scores at the last follow-up. However, there was a significant difference in the failure rate after operation between the 2 groups (P = .039). In the first-time dislocation group, 1 patient had redislocation and none showed positive apprehension. In the recurrent dislocation group, 6 patients had redislocation and 10 patients had positive apprehension. Eight of 10 patients who showed positive apprehension had either anterior labral periosteal sleeve avulsion lesions or anterior glenoid erosion. The patients' satisfaction with daily activities was significantly better in the first-time dislocation group (93.0 +/- 5.2) than in the recurrent dislocation group (82.7 +/- 7.2; P < .001). CONCLUSIONS: Primary surgical treatment for first time traumatic anterior shoulder dislocation provided satisfactory functional outcomes and improved quality of life. Primary arthroscopic stabilization can be considered one of the treatment options in patients younger than 30 years with first-time shoulder dislocation to prevent further intra-articular injuries that may contribute to recurrence. PMID- 27260996 TI - Heterotopic ossification of the long head of the triceps after reverse total shoulder arthroplasty. AB - BACKGROUND: Heterotopic ossification (HO) around shoulder arthroplasty is a frequent finding with unclear clinical relevance. This study evaluated the incidence, relevance, and predisposing factors of HO in the long head of the triceps tendon after reverse shoulder arthroplasty. METHODS: Retrospective chart review was conducted to identify patients who had a reverse shoulder arthroplasty performed between 2008 and 2012. Patient demographics, implant types, and diagnoses were noted. Three fellowship-trained shoulder/elbow surgeons independently evaluated postoperative Grashey radiographs using a novel classification system. RESULTS: Within a 164-patient cohort, the overall HO rate in the long head of the triceps tendon was 61.6%; 23.2% of osteophytes were considered impinging, 14.6% had notching, 14.0% were free-floating, and 3.0% appeared ankylosed. Although not statistically significant, revision surgery had a higher rate of HO (68.3%) compared with primary surgery (59.4%). There was no difference in HO rates between diagnoses or implant types. Male and female HO rates were 74.0% and 56.1%, respectively (P = .0304). Between patients with and without HO, forward elevation was 121 degrees compared with 133 degrees (P = .0087) and external rotation was 19 degrees compared with 25 degrees (P = .0266); however, HO size did not significantly affect motion. CONCLUSIONS: Using our novel classification scheme, HO was a common finding in this series. Men had a higher rate of HO formation, and HO formation was associated with worse postoperative motion. Further study is needed to fully characterize the clinical implications of HO involving the long head of the triceps tendon and to explore potential preventive measures. PMID- 27260997 TI - Patient resistance as a resource: candidate obstacles in diabetes consultations. AB - This study uses conversation analysis to explore 'candidate obstacles', a practice observed in sequences of patient resistance to lifestyle advice within health professional consultations. This article presents illustrative analyses of selected data excerpts drawn from audio-visual recordings of 116 tracked consultations between health professionals and 34 patients newly diagnosed with type 2 diabetes mellitus in New Zealand. The analysis shows that in consultations where health promotion activities are central, patient resistance can provide space for patients to identify obstacles to their compliance with lifestyle advice. Identifying candidate obstacles provides opportunities for health professionals to align advice with concerns of patients and potentially improve patient outcomes. PMID- 27260998 TI - Lipotoxicity: Many Roads to Cell Dysfunction and Cell Death: Introduction to a Thematic Review Series. PMID- 27260999 TI - A Genome-Wide Screen for Dendritically Localized RNAs Identifies Genes Required for Dendrite Morphogenesis. AB - Localizing messenger RNAs at specific subcellular sites is a conserved mechanism for targeting the synthesis of cytoplasmic proteins to distinct subcellular domains, thereby generating the asymmetric protein distributions necessary for cellular and developmental polarity. However, the full range of transcripts that are asymmetrically distributed in specialized cell types, and the significance of their localization, especially in the nervous system, are not known. We used the EP-MS2 method, which combines EP transposon insertion with the MS2/MCP in vivo fluorescent labeling system, to screen for novel localized transcripts in polarized cells, focusing on the highly branched Drosophila class IV dendritic arborization neurons. Of a total of 541 lines screened, we identified 55 EP-MS2 insertions producing transcripts that were enriched in neuronal processes, particularly in dendrites. The 47 genes identified by these insertions encode molecularly diverse proteins, and are enriched for genes that function in neuronal development and physiology. RNAi-mediated knockdown confirmed roles for many of the candidate genes in dendrite morphogenesis. We propose that the transport of mRNAs encoded by these genes into the dendrites allows their expression to be regulated on a local scale during the dynamic developmental processes of dendrite outgrowth, branching, and/or remodeling. PMID- 27261000 TI - A Population of Deletion Mutants and an Integrated Mapping and Exome-seq Pipeline for Gene Discovery in Maize. AB - To better understand maize endosperm filling and maturation, we used gamma irradiation of the B73 maize reference line to generate mutants with opaque endosperm and reduced kernel fill phenotypes, and created a population of 1788 lines including 39 Mo17 * F2s showing stable, segregating, and viable kernel phenotypes. For molecular characterization of the mutants, we developed a novel functional genomics platform that combined bulked segregant RNA and exome sequencing (BSREx-seq) to map causative mutations and identify candidate genes within mapping intervals. To exemplify the utility of the mutants and provide proof-of-concept for the bioinformatics platform, we present detailed characterization of line 937, an opaque mutant harboring a 6203 bp in-frame deletion covering six exons within the Opaque-1 gene. In addition, we describe mutant line 146 which contains a 4.8 kb intragene deletion within the Sugary-1 gene and line 916 in which an 8.6 kb deletion knocks out a Cyclin A2 gene. The publically available algorithm developed in this work improves the identification of causative deletions and its corresponding gaps within mapping peaks. This study demonstrates the utility of gamma-irradiation for forward genetics in large nondense genomes such as maize since deletions often affect single genes. Furthermore, we show how this classical mutagenesis method becomes applicable for functional genomics when combined with state-of-the-art genomics tools. PMID- 27261001 TI - A Genetic Screen for Mutants with Supersized Lipid Droplets in Caenorhabditis elegans. AB - To identify genes that regulate the dynamics of lipid droplet (LD) size, we have used the genetically tractable model organism Caenorhabditis elegans, whose wild type LD population displays a steady state of size with an upper limit of 3 MUm in diameter. From a saturated forward genetic screen of 6.7 * 10(5) mutagenized haploid genomes, we isolated 118 mutants with supersized intestinal LDs often reaching 10 MUm. These mutants define nine novel complementation groups, in addition to four known genes (maoc-1, dhs-28, daf-22, and prx-10). The nine groups are named drop (lipid droplet abnormal) and categorized into four classes. Class I mutants drop-5 and drop-9, similar to prx-10, are up-regulated in ACS-22 DGAT-2-dependent LD growth, resistant to LD hydrolysis, and defective in peroxisome import. Class II mutants drop-2, drop-3, drop-6, and drop-7 are up regulated in LD growth, are resistant to LD hydrolysis, but are not defective in peroxisome import. Class III mutants drop-1 and drop-8 are neither up-regulated in LD growth nor resistant to LD hydrolysis, but seemingly up-regulated in LD fusion. Class IV mutant drop-4 is cloned as sams-1 and, different to the other three classes, is ACS-22-independent and hydrolysis-resistant. These four classes of supersized LD mutants should be valuable for mechanistic studies of LD cellular processes including growth, hydrolysis, and fusion. PMID- 27261003 TI - MeSH-Informed Enrichment Analysis and MeSH-Guided Semantic Similarity Among Functional Terms and Gene Products in Chicken. AB - Biomedical vocabularies and ontologies aid in recapitulating biological knowledge. The annotation of gene products is mainly accelerated by Gene Ontology (GO), and more recently by Medical Subject Headings (MeSH). Here, we report a suite of MeSH packages for chicken in Bioconductor, and illustrate some features of different MeSH-based analyses, including MeSH-informed enrichment analysis and MeSH-guided semantic similarity among terms and gene products, using two lists of chicken genes available in public repositories. The two published datasets that were employed represent (i) differentially expressed genes, and (ii) candidate genes under selective sweep or epistatic selection. The comparison of MeSH with GO overrepresentation analyses suggested not only that MeSH supports the findings obtained from GO analysis, but also that MeSH is able to further enrich the representation of biological knowledge and often provide more interpretable results. Based on the hierarchical structures of MeSH and GO, we computed semantic similarities among vocabularies, as well as semantic similarities among selected genes. These yielded the similarity levels between significant functional terms, and the annotation of each gene yielded the measures of gene similarity. Our findings show the benefits of using MeSH as an alternative choice of annotation in order to draw biological inferences from a list of genes of interest. We argue that the use of MeSH in conjunction with GO will be instrumental in facilitating the understanding of the genetic basis of complex traits. PMID- 27261002 TI - Transcriptome Profiling Identifies Multiplexin as a Target of SAGA Deubiquitinase Activity in Glia Required for Precise Axon Guidance During Drosophila Visual Development. AB - The Spt-Ada-Gcn5 Acetyltransferase (SAGA) complex is a transcriptional coactivator with histone acetylase and deubiquitinase activities that plays an important role in visual development and function. In Drosophila melanogaster, four SAGA subunits are required for the deubiquitination of monoubiquitinated histone H2B (ubH2B): Nonstop, Sgf11, E(y)2, and Ataxin 7. Mutations that disrupt SAGA deubiquitinase activity cause defects in neuronal connectivity in the developing Drosophila visual system. In addition, mutations in SAGA result in the human progressive visual disorder spinocerebellar ataxia type 7 (SCA7). Glial cells play a crucial role in both the neuronal connectivity defect in nonstop and sgf11 flies, and in the retinal degeneration observed in SCA7 patients. Thus, we sought to identify the gene targets of SAGA deubiquitinase activity in glia in the Drosophila larval central nervous system. To do this, we enriched glia from wild-type, nonstop, and sgf11 larval optic lobes using affinity-purification of KASH-GFP tagged nuclei, and then examined each transcriptome using RNA-seq. Our analysis showed that SAGA deubiquitinase activity is required for proper expression of 16% of actively transcribed genes in glia, especially genes involved in proteasome function, protein folding and axon guidance. We further show that the SAGA deubiquitinase-activated gene Multiplexin (Mp) is required in glia for proper photoreceptor axon targeting. Mutations in the human ortholog of Mp, COL18A1, have been identified in a family with a SCA7-like progressive visual disorder, suggesting that defects in the expression of this gene in SCA7 patients could play a role in the retinal degeneration that is unique to this ataxia. PMID- 27261004 TI - Septate Junction Proteins Play Essential Roles in Morphogenesis Throughout Embryonic Development in Drosophila. AB - The septate junction (SJ) is the occluding junction found in the ectodermal epithelia of invertebrate organisms, and is essential to maintain chemically distinct compartments in epithelial organs, to provide the blood-brain barrier in the nervous system, and to provide an important line of defense against invading pathogens. More than 20 genes have been identified to function in the establishment or maintenance of SJs in Drosophila melanogaster Numerous studies have demonstrated the cell biological function of these proteins in establishing the occluding junction, whereas very few studies have examined further developmental roles for them. Here we examined embryos with mutations in nine different core SJ genes and found that all nine result in defects in embryonic development as early as germ band retraction, with the most penetrant defect observed in head involution. SJ genes are also required for cell shape changes and cell rearrangements that drive the elongation of the salivary gland during midembryogenesis. Interestingly, these developmental events occur at a time prior to the formation of the occluding junction, when SJ proteins localize along the lateral membrane and have not yet coalesced into the region of the SJ. Together, these observations reveal an underappreciated role for a large group of SJ genes in essential developmental events during embryogenesis, and suggest that the function of these proteins in facilitating cell shape changes and rearrangements is independent of their role in the occluding junction. PMID- 27261005 TI - Mutations in Dnaaf1 and Lrrc48 Cause Hydrocephalus, Laterality Defects, and Sinusitis in Mice. AB - We have previously described a forward genetic screen in mice for abnormalities of brain development. Characterization of two hydrocephalus mutants by whole exome sequencing after whole-genome SNP mapping revealed novel recessive mutations in Dnaaf1 and Lrrc48 Mouse mutants of these two genes have not been previously reported. The Dnaaf1 mutant carries a mutation at the splice donor site of exon 4, which results in abnormal transcripts. The Lrrc48 mutation is a missense mutation at a highly conserved leucine residue, which is also associated with a decrease in Lrrc48 transcription. Both Dnaaf1 and Lrrc48 belong to a leucine-rich repeat-containing protein family and are components of the ciliary axoneme. Their Chlamydomonas orthologs are known to be required for normal ciliary beat frequency or flagellar waveform, respectively. Some Dnaaf1 or Lrrc48 homozygote mutants displayed laterality defects, suggesting a motile cilia defect in the embryonic node. Mucus accumulation and neutrophil infiltration in the maxillary sinuses suggested sinusitis. Dnaaf1 mutants showed postnatal lethality, and none survived to weaning age. Lrrc48 mutants survive to adulthood, but had male infertility. ARL13B immunostaining showed the presence of motile cilia in the mutants, and the distal distribution of DNAH9 in the axoneme of upper airway motile cilia appeared normal. The phenotypic abnormalities suggest that mutations in Dnaaf1 and Lrrc48 cause defects in motile cilia function. PMID- 27261006 TI - Characterization of a Single Genomic Locus Encoding the Clustered Protocadherin Receptor Diversity in Xenopus tropicalis. AB - Clustered protocadherins (cPcdhs) constitute the largest subgroup of the cadherin superfamily, and in mammals are grouped into clusters of alpha-, beta-, and gamma types. Tens of tandemly arranged paralogous Pcdh genes of the Pcdh clusters generate a substantial diversity of receptor isoforms. cPcdhs are known to have important roles in neuronal development, and genetic alterations of cPcdhs have been found to be associated with several neurological diseases. Here, we present a first characterization of cPcdhs in Xenopus tropicalis We determined and annotated all cPcdh isoforms, revealing that they are present in a single chromosomal locus. We validated a total of 96 isoforms, which we show are organized in three distinct clusters. The X. tropicalis cPcdh locus is composed of one alpha- and two distinct gamma-Pcdh clusters (pcdh-gamma1 and pcdh-gamma2). Bioinformatics analyses assisted by genomic BAC clone sequencing showed that the X. tropicalis alpha- and gamma-Pcdhs are conserved at the cluster level, but, unlike mammals, X. tropicalis does not contain a beta-Pcdh cluster. In contrast, the number of gamma-Pcdh isoforms has expanded, possibly due to lineage-specific gene duplications. Interestingly, the number of X. tropicalis alpha-Pcdhs is identical between X. tropicalis and mouse. Moreover, we find highly conserved as well as novel promoter elements potentially involved in regulating the cluster specific expression of cPcdh isoforms. This study provides important information for the understanding of the evolutionary history of cPcdh genes and future mechanistic studies. It provides an annotated X. tropicalis cPcdh genomic map and a first molecular characterization essential for functional and comparative studies. PMID- 27261007 TI - Relationships Between RNA Polymerase II Activity and Spt Elongation Factors to Spt- Phenotype and Growth in Saccharomyces cerevisiae. AB - The interplay between adjacent transcription units can result in transcription dependent alterations in chromatin structure or recruitment of factors that determine transcription outcomes, including the generation of intragenic or other cryptic transcripts derived from cryptic promoters. Mutations in a number of genes in Saccharomyces cerevisiae confer both cryptic intragenic transcription and the Suppressor of Ty (Spt(-)) phenotype for the lys2-128? allele of the LYS2 gene. Mutants that suppress lys2-128? allow transcription from a normally inactive Ty1 ? promoter, conferring a LYS(+) phenotype. The arrangement of transcription units at lys2-128? is reminiscent of genes containing cryptic promoters within their open reading frames. We set out to examine the relationship between RNA Polymerase II (Pol II) activity, functions of Spt elongation factors, and cryptic transcription because of the previous observation that increased-activity Pol II alleles confer an Spt(-) phenotype. We identify both cooperating and antagonistic genetic interactions between Pol II alleles and alleles of elongation factors SPT4, SPT5, and SPT6 We find that cryptic transcription at FLO8 and STE11 is distinct from that at lys2-128?, though all show sensitivity to reduction in Pol II activity, especially the expression of lys2-128? found in Spt(-) mutants. We determine that the lys2-128? Spt(-) phenotypes for spt6-1004 and increased activity rpo21/rpb1 alleles each require transcription from the LYS2 promoter. Furthermore, we identify the Ty1 transcription start site (TSS) within the ? element as the position of Spt(-) transcription in tested Spt(-) mutants. PMID- 27261055 TI - Perceived needs for mental health care and barriers to treatment across age groups. AB - PURPOSE: This study aimed to assess responses to a structured measure of perceived need for treatment to understand whether differences in treatment uptake across age groups are related to differences in: (1) perceived need for mental health care; (2) perceptions of treatment needs being met; and/or (3) perceived attitudinal and structural treatment barriers. METHODS: Data from a nationally representative sample of the Australian population (2007 National Survey of Mental Health and Wellbeing) were analysed using logistic and multinomial regression. All participants potentially benefiting from mental health services were included in analyses; including those reporting symptoms of mental disorders, using mental health services, or self-reporting significant mental health problems in the past 12 months (n = 5733). All regression analyses were adjusted for gender, the presence of chronic physical health conditions, disorder type, and disorder severity. RESULTS: Older adults were the least likely to report any perceived need for mental health care, and specifically reported lower needs for psychotherapy, information about available services, and support improving their ability to work. Older adults perceiving a need for mental health care were also the most likely to report having these needs met. There were no differences in attitudinal and structural barriers to treatment across age groups. CONCLUSIONS: These results highlight that age needs to be considered in strategies for improving engagement and efficacy of mental health services, as well as the need for further research to understand what drives age differences in perceived need for mental health care. PMID- 27261008 TI - Achieving Synergy: Linking an Internet-Based Inflammatory Bowel Disease Cohort to a Community-Based Inception Cohort and Multicentered Cohort in Inflammatory Bowel Disease. AB - BACKGROUND: Traditional cohort studies are important contributors to our understanding of inflammatory bowel diseases, but they are labor intensive and often do not focus on patient-reported outcomes. Internet-based studies provide new opportunities to study patient-reported outcomes and can be efficiently implemented and scaled. If a traditional cohort study was linked to an Internet based study, both studies could benefit from added synergy. Existing cohort studies provide an opportunity to develop and test processes for cohort linkage. The Crohn's and Colitis Foundation of America's (CCFA) Partners study is an Internet-based cohort of more than 14,000 participants. The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is an inception cohort. The Sinai-Helmsley Alliance for Research Excellence (SHARE) is a multicentered cohort of inflammatory bowel disease patients. Both the later cohorts include medical record abstraction, patient surveys, and biospecimen collection. OBJECTIVE: Given the complementary nature of these existing cohorts, we sought to corecruit and link data. METHODS: Eligible OSCCAR and SHARE participants were invited to join the CCFA Partners study and provide consent for data sharing between the 2 cohorts. After informed consent, participants were directed to the CCFA Partners website to complete enrollment and a baseline Web-based survey. Participants were linked across the 2 cohorts by the matching of an email address. We compared demographic and clinical characteristics between OSCCAR and SHARE participants who did and did not enroll in CCFA Partners and the data linkage. RESULTS: Of 408 participants in the OSCCAR cohort, 320 were eligible for participation in the CCFA Partners cohort. Of these participants, 243 consented to participation; however, only 44 enrolled in CCFA Partners and completed the linkage. OSCCAR participants who enrolled in CCFA Partners were better educated (17% with doctoral degrees) than those who did not (3% with doctoral degrees, P=.01). In the SHARE cohort, 436 participants enrolled and linked to the Partners cohort. More women (60% vs 50%) linked and those who linked were predominantly white (96%; P<.01). Crohn's disease patients who linked had lower mean scores on the Harvey-Bradshaw Index (3.6 vs 4.4, P<.01). Ulcerative colitis patients who linked had less extensive disease than those who did not link (45% vs 60%, P<.01). CONCLUSIONS: Linkage of CCFA Partners with cohorts such as OSCCAR and SHARE may be a cost-effective way to expand the infrastructure for clinical outcomes and translational research. Although linkage is feasible from a technical, legal, and regulatory perspective, participant willingness appears to be a limiting factor. Overcoming this barrier will be needed to generate meaningful sample sizes to conduct studies of biomarkers, natural history, and clinical effectiveness using linked data. PMID- 27261056 TI - Taking Aim at the Cognitive Side of Learning in Sensorimotor Adaptation Tasks. AB - Sensorimotor adaptation tasks have been used to characterize processes responsible for calibrating the mapping between desired outcomes and motor commands. Research has focused on how this form of error-based learning takes place in an implicit and automatic manner. However, recent work has revealed the operation of multiple learning processes, even in this simple form of learning. This review focuses on the contribution of cognitive strategies and heuristics to sensorimotor learning, and how these processes enable humans to rapidly explore and evaluate novel solutions to enable flexible, goal-oriented behavior. This new work points to limitations in current computational models, and how these must be updated to describe the conjoint impact of multiple processes in sensorimotor learning. PMID- 27261057 TI - The Functional Anatomy of Time: What and When in the Brain. AB - This Opinion article considers the implications for functional anatomy of how we represent temporal structure in our exchanges with the world. It offers a theoretical treatment that tries to make sense of the architectural principles seen in mammalian brains. Specifically, it considers a factorisation between representations of temporal succession and representations of content or, heuristically, a segregation into when and what. This segregation may explain the central role of the hippocampus in neuronal hierarchies while providing a tentative explanation for recent observations of how ordinal sequences are encoded. The implications for neuroanatomy and physiology may have something important to say about how self-organised cell assembly sequences enable the brain to exhibit purposeful behaviour that transcends the here and now. PMID- 27261058 TI - Effects of prenatal substance exposure on neurocognitive correlates of inhibitory control success and failure. AB - Adolescents with prenatal substance (drug and alcohol) exposure exhibit inhibitory control (IC) deficits and aberrations in associated neural function. Nearly all research to date examines exposure to individual substances, and a minimal amount is known about the effects of heterogeneous exposure-which is more representative of population exposure levels. Using functional magnetic resonance imaging (fMRI), we investigated IC (Go/NoGo) in heterogeneously exposed (n = 7) vs. control (n = 7) at-risk adolescents (ages 13-17). The fMRI results indicated multiple IC processing differences consistent with a more immature developmental profile for exposed adolescents (Exposed > Nonexposed: NoGo > Go: right ventrolateral prefrontal cortex, right cuneus, and left inferior parietal lobe; NoGo > false alarm: occipital lobe; Go > false alarm: right anterior prefrontal cortex). Simple effects suggest exposed adolescents exhibited exaggerated correct trial but decreased incorrect trial activation. Results provide initial evidence that prenatal exposure across substances creates similar patterns of atypical brain activation to IC success and failure. PMID- 27261059 TI - Effects of abnormal temperature and starvation on the internal defense system of the schistosome-transmitting snail Biomphalaria glabrata. AB - Climate change may affect the internal defense system (IDS) of freshwater snails, and as a result their capacity to transmit disease. We examined effects of short term exposure to supra- and sub-optimal temperatures or starvation on 3 parameters of the IDS of the schistosome-resistant Salvador strain of Biomphalaria glabrata - hemocyte concentrations, cell division in the amebocyte producing organ (APO), and resistance to infection with Schistosoma mansoni. Adult snails were exposed to 1 of 3 temperatures, 20 degrees C, 27 degrees C (controls), or 33 degrees C, for 1 or 2weeks, with food. A fourth group was maintained at 27 degrees C, but without food. Compared to the controls, starved snails had significantly higher hemocyte counts at both 1 and 2weeks, although mitotic activity in the APO was significantly lower at both time periods. Exposure to 20 degrees C or 33 degrees C for 1 or 2weeks did not affect hemocyte numbers. However, APO mitotic activity in snails exposed to 20 degrees C was significantly higher at both 1 and 2weeks, whereas mitotic activity in snails exposed to 33 degrees C was significantly lower at 1week but normal at 2weeks. None of the treatments altered the resistance phenotype of Salvador snails. In a follow-up experiment, exposure to 33 degrees C for 4-5h, a treatment previously reported to both induce expression of heat shock proteins (Hsps) and abrogate resistance to infection, caused immediate upregulation of Hsp 70 and Hsp 90 expression, but did not alter resistance, and Hsp expression levels returned to baseline after 2weeks at 33 degrees C. Results of this study indicate that abnormal environmental conditions can have both stimulatory and inhibitory effects on the IDS in adult B. glabrata, and that some degree of acclimation to abnormal temperatures may occur. PMID- 27261060 TI - Gene expression patterns in response to pathogen challenge and interaction with hemolin suggest that the Yippee protein of Antheraea pernyi is involved in the innate immune response. AB - Yippee was first identified as a protein that physically interacts with the Hemolin protein of Hyalophora cecropia. In this study, we identified a gene with a 366bp open reading frame (ORF) that encodes a 121 amino acid protein containing a conserved Yippee domain. We named this gene Ap-Yippee (Yippee gene from Antheraea pernyi), and investigated the role of the protein in the host immune response. A recombinant Ap-Yippee protein was expressed in Escherichia coli cells, and polyclonal antibodies were produced against the recombinant protein. Real-time PCR and a Western blot analysis revealed that Ap-Yippee is expressed in the hemocytes, Malpighian tubules, midgut, silk gland, epidermis, and fat bodies of A. pernyi, with the highest expression level observed in Malpighian tubules. The fifth instar larvae of A. pernyi were challenged by injecting them with nucleopolyhedrovirus (AP-NPV), the Gram-negative bacterium E. coli, the Gram positive bacterium Micrococcus luteus, or the entomopathogenic fungus, Beauveria bassiana. These challenges with diverse pathogens resulted in differential expression patterns of the protein. A knockdown of the Ap-Yippee gene by small interfering RNA (siRNA) transfection had a significant influence on the expression of the hemolin in the pupae which was confirmed by qRT-PCR and Western blot. Furthermore, a possible protein-protein interaction between Ap-Yippee and Hemolin was explored by Far-Western blotting. Therefore, our data suggest that the Ap-Yippee protein is involved in a pathway that regulates the immune response of insects. PMID- 27261061 TI - Preliminary evaluation of a differential effect of an alpha-linolenate-rich supplement on ketogenesis and plasma omega-3 fatty acids in young and older adults. AB - OBJECTIVES: The aim of the present study was to compare the effects of an alpha linolenic acid-rich supplement (ALA-RS) on the ketogenic response and plasma long chain omega-3 polyunsaturated fatty acid in healthy young adults and older individuals. METHODS: Ten young (25 +/- 0.9 y) and 10 older adults (73.1 +/- 2.2 y) consumed a flaxseed oil supplement providing 2 g/d of ALA for 4 wk. Plasma ketones, nonesterified fatty acids (NEFA), triacylglycerols, glucose, and insulin were measured over 6 h, before and after supplementation. Total body fat mass was assessed before and after the ALA-RS. RESULTS: The ALA-RS did not significantly modify fasting ketones but postprandial production of beta-hydroxybutyrate was increased by 26% (P = 0.037) only in the young adult group. Fasting plasma ketones were positively correlated to fasting plasma NEFA (P < 0.01) in both groups. However, the relation was shifted to the right in the older group, suggesting that older adults needed higher plasma NEFA levels to achieve the same ketone amounts as young adults. At baseline, the older group had 47% higher total plasma fatty acids than the young group (P = 0.007). After the ALA-RS, plasma ALA doubled in both groups (P < 0.01), an effect that was associated in the older group with a 40% higher eicosapentaenoic acid (EPA; P = 0.004), but no difference in docosahexaenoic acid. The postsupplementation increase in plasma ALA correlated positively with percent total body fat, especially in the older group (r(2) = 0.77; P = 0.0016). CONCLUSION: In young adults, ALA-RS mildly stimulated postprandial ketogenesis, whereas in the older group, it favored increased plasma ALA and EPA. PMID- 27261062 TI - A high visceral adipose tissue-to-skeletal muscle ratio as a determinant of major complications after pancreatoduodenectomy for cancer. AB - OBJECTIVE: Complication rates after pancreatic resections remain high despite improvement in perioperative management. The effects of body composition and the relationship among different body compartments on surgical morbidity are not comprehensively investigated. The aim of this study was to assess whether the evaluation of different body compartments and their relationship was associated with the development of major postoperative complications after pancreatoduodenectomy (PD) for cancer. METHODS: We retrospectively analyzed 124 patients who underwent PD and had a staging computed tomography (CT) scan at our center. CT scan was used to measure abdominal skeletal muscle area and volume, as well as visceral fat area (VFA) and volume. The total abdominal muscle area (TAMA) was then normalized for height. The severity of complications was assessed. Univariate and multivariate analyses were performed to investigate correlations between the above variables and postoperative complications. The receiver operating characteristic curve methodology was used to investigate the predictive ability of each parameter. RESULTS: Major complications occurred in 42 patients (33.9%). The prevalence of sarcopenia was 24.2%. Regression analyses revealed no correlation between abdominal muscular and adipose tissue areas. Univariate analysis showed that the depletion of muscle area normalized for height was not per se predictive of complications (P = 0.318). Multivariate logistic regression showed that the VFA/TAMA was the only determinant of major complications (odds ratio, 3.20; 95% confidence interval, 1.35-7.60; P = 0.008). The model predictive performance was 0.735 (area under the curve) with a sensitivity of 64.3% and a specificity of 74.4%. CONCLUSION: Sarcopenic obesity is a strong predictor of major complications after PD for cancer. PMID- 27261063 TI - The Plasma Membrane H+-ATPase AHA1 Plays a Major Role in Stomatal Opening in Response to Blue Light. AB - Stomata open in response to a beam of weak blue light under strong red light illumination. A blue light signal is perceived by phototropins and transmitted to the plasma membrane H(+)-ATPase that drives stomatal opening. To identify the components in this pathway, we screened for mutants impaired in blue light dependent stomatal opening. We analyzed one such mutant, provisionally named blus2 (blue light signaling2), and found that stomatal opening in leaves was impaired by 65%, although the magnitude of red light-induced opening was not affected. Blue light-dependent stomatal opening in the epidermis and H(+) pumping in guard cell protoplasts were inhibited by 70% in blus2 Whole-genome resequencing identified a mutation in the AHA1 gene of the mutant at Gly-602. T DNA insertion mutants of AHA1 exhibited a similar phenotype to blus2; this phenotype was complemented by the AHA1 gene. We renamed blus2 as aha1-10 T-DNA insertion mutants of AHA2 and AHA5 did not show any impairment in stomatal response, although the transcript levels of AHA2 and AHA5 were higher than those of AHA1 in wild-type guard cells. Stomata in ost2, a constitutively active AHA1 mutant, did not respond to blue light. A decreased amount of H(+)-ATPase in aha1 10 accounted for the reduced stomatal blue light responses and the decrease was likely caused by proteolysis of misfolded AHA1. From these results, we conclude that AHA1 plays a major role in blue light-dependent stomatal opening in Arabidopsis and that the mutation made the AHA1 protein unstable in guard cells. PMID- 27261064 TI - A Collection of Conserved Noncoding Sequences to Study Gene Regulation in Flowering Plants. AB - Transcription factors (TFs) regulate gene expression by binding cis-regulatory elements, of which the identification remains an ongoing challenge owing to the prevalence of large numbers of nonfunctional TF binding sites. Powerful comparative genomics methods, such as phylogenetic footprinting, can be used for the detection of conserved noncoding sequences (CNSs), which are functionally constrained and can greatly help in reducing the number of false-positive elements. In this study, we applied a phylogenetic footprinting approach for the identification of CNSs in 10 dicot plants, yielding 1,032,291 CNSs associated with 243,187 genes. To annotate CNSs with TF binding sites, we made use of binding site information for 642 TFs originating from 35 TF families in Arabidopsis (Arabidopsis thaliana). In three species, the identified CNSs were evaluated using TF chromatin immunoprecipitation sequencing data, resulting in significant overlap for the majority of data sets. To identify ultraconserved CNSs, we included genomes of additional plant families and identified 715 binding sites for 501 genes conserved in dicots, monocots, mosses, and green algae. Additionally, we found that genes that are part of conserved mini-regulons have a higher coherence in their expression profile than other divergent gene pairs. All identified CNSs were integrated in the PLAZA 3.0 Dicots comparative genomics platform (http://bioinformatics.psb.ugent.be/plaza/versions/plaza_v3_dicots/) together with new functionalities facilitating the exploration of conserved cis regulatory elements and their associated genes. The availability of this data set in a user-friendly platform enables the exploration of functional noncoding DNA to study gene regulation in a variety of plant species, including crops. PMID- 27261065 TI - Alarm Photosynthesis: Calcium Oxalate Crystals as an Internal CO2 Source in Plants. AB - Calcium oxalate crystals are widespread among animals and plants. In land plants, crystals often reach high amounts, up to 80% of dry biomass. They are formed within specific cells, and their accumulation constitutes a normal activity rather than a pathological symptom, as occurs in animals. Despite their ubiquity, our knowledge on the formation and the possible role(s) of these crystals remains limited. We show that the mesophyll crystals of pigweed (Amaranthus hybridus) exhibit diurnal volume changes with a gradual decrease during daytime and a total recovery during the night. Moreover, stable carbon isotope composition indicated that crystals are of nonatmospheric origin. Stomatal closure (under drought conditions or exogenous application of abscisic acid) was accompanied by crystal decomposition and by increased activity of oxalate oxidase that converts oxalate into CO2 Similar results were also observed under drought stress in Dianthus chinensis, Pelargonium peltatum, and Portulacaria afra Moreover, in A. hybridus, despite closed stomata, the leaf metabolic profiles combined with chlorophyll fluorescence measurements indicated active photosynthetic metabolism. In combination, calcium oxalate crystals in leaves can act as a biochemical reservoir that collects nonatmospheric carbon, mainly during the night. During the day, crystal degradation provides subsidiary carbon for photosynthetic assimilation, especially under drought conditions. This new photosynthetic path, with the suggested name "alarm photosynthesis," seems to provide a number of adaptive advantages, such as water economy, limitation of carbon losses to the atmosphere, and a lower risk of photoinhibition, roles that justify its vast presence in plants. PMID- 27261066 TI - A ROS-Assisted Calcium Wave Dependent on the AtRBOHD NADPH Oxidase and TPC1 Cation Channel Propagates the Systemic Response to Salt Stress. AB - Plants exhibit rapid, systemic signaling systems that allow them to coordinate physiological and developmental responses throughout the plant body, even to highly localized and quickly changing environmental stresses. The propagation of these signals is thought to include processes ranging from electrical and hydraulic networks to waves of reactive oxygen species (ROS) and cytoplasmic Ca(2+) traveling throughout the plant. For the Ca(2+) wave system, the involvement of the vacuolar ion channel TWO PORE CHANNEL1 (TPC1) has been reported. However, the precise role of this channel and the mechanism of cell-to cell propagation of the wave have remained largely undefined. Here, we use the fire-diffuse-fire model to analyze the behavior of a Ca(2+) wave originating from Ca(2+) release involving the TPC1 channel in Arabidopsis (Arabidopsis thaliana). We conclude that a Ca(2+) diffusion-dominated calcium-induced calcium-release mechanism is insufficient to explain the observed wave transmission speeds. The addition of a ROS-triggered element, however, is able to quantitatively reproduce the observed transmission characteristics. The treatment of roots with the ROS scavenger ascorbate and the NADPH oxidase inhibitor diphenyliodonium and analysis of Ca(2+) wave propagation in the Arabidopsis respiratory burst oxidase homolog D (AtrbohD) knockout background all led to reductions in Ca(2+) wave transmission speeds consistent with this model. Furthermore, imaging of extracellular ROS production revealed a systemic spread of ROS release that is dependent on both AtRBOHD and TPC1 These results suggest that, in the root, plant systemic signaling is supported by a ROS-assisted calcium-induced calcium-release mechanism intimately involving ROS production by AtRBOHD and Ca(2+) release dependent on the vacuolar channel TPC1. PMID- 27261068 TI - Maternal influenza immunisation in resource-limited settings. PMID- 27261069 TI - The "Ethics" Expertise in Clinical Ethics Consultation. AB - The nature, possibility, and implications of ethics expertise (or moral expertise) in general and of bioethics expertise in particular has been the focus of extensive debate for over thirty years. What is ethics expertise and what does it enable experts to do? Knowing what ethics expertise is can help answer another important question: What, if anything, makes a claim of expertise legitimate? In other words, how does someone earn the appellation "ethics expert?" There remains deep disagreement on whether ethics expertise is possible, and if so, what constitutes such expertise and what it entails and legitimates. Discussion of bioethics expertise has become particularly important given the growing presence of bioethicists in the clinical setting as well as efforts to professionalize bioethics through codes of ethics and certification (or quasi-certification) efforts. Unlike in the law or in engineering, where there may be a body of knowledge that professional organizations or others have articulated as important for education and training of experts, ethics expertise admits of no such body of knowledge or required experience. Nor is there an entity seen as having the authority to articulate the necessary scope of knowledge. Questions about whether there is such a body of knowledge for particular areas within bioethics have emerged and played a central role in professionalization efforts in recent years, especially in the area of clinical ethics. PMID- 27261067 TI - Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer blind, randomised phase 4 trial. AB - BACKGROUND: Despite the heightened risk of serious influenza during infancy, vaccination is not recommended in infants younger than 6 months. We aimed to assess the safety, immunogenicity, and efficacy of maternal immunisation with trivalent inactivated influenza vaccine for protection of infants against a first episode of laboratory-confirmed influenza. METHODS: We did this prospective, active-controlled, observer-blind, randomised phase 4 trial at six referral centres and community health centres in Bamako, Mali. Third-trimester pregnant women (>=28 weeks' gestation) were randomly assigned (1:1), via a computer generated, centre-specific list with alternate block sizes of six or 12, to receive either trivalent inactivated influenza vaccine or quadrivalent meningococcal vaccine. Study personnel administering vaccines were not masked to treatment allocation, but allocation was concealed from clinicians, laboratory personnel, and participants. Infants were visited weekly until age 6 months to detect influenza-like illness; laboratory-confirmed influenza diagnosed with RT PCR. We assessed two coprimary objectives: vaccine efficacy against laboratory confirmed influenza in infants born to women immunised any time prepartum (intention-to-treat population), and vaccine efficacy in infants born to women immunised at least 14 days prepartum (per-protocol population). The primary outcome was the occurrence of a first case of laboratory-confirmed influenza by age 6 months. This trial is registered with ClinicalTrials.gov, number NCT01430689. FINDINGS: We did this trial from Sept 12, 2011, to Jan 28, 2014. Between Sept 12, 2011, and April 18, 2013, we randomly assigned 4193 women to receive trivalent inactivated influenza vaccine (n=2108) or quadrivalent meningococcal vaccine (n=2085). There were 4105 livebirths; 1797 (87%) of 2064 infants in the trivalent inactivated influenza vaccine group and 1793 (88%) of 2041 infants in the quadrivalent meningococcal vaccine group were followed up until age 6 months. We recorded 5279 influenza-like illness episodes in 2789 (68%) infants, of which 131 (2%) episodes were laboratory-confirmed influenza. 129 (98%) cases of laboratory-confirmed influenza were first episodes (n=77 in the quadrivalent meningococcal vaccine group vs n=52 in the trivalent inactivated influenza vaccine group). In the intention-to-treat population, overall infant vaccine efficacy was 33.1% (95% CI 3.7-53.9); in the per-protocol population, vaccine efficacy was 37.3% (7.6-57.8). Vaccine efficacy remained robust during the first 4 months of follow-up (67.9% [95% CI 35.1-85.3] by intention to treat and 70.2% [35.7-87.6] by per protocol), before diminishing during the fifth month (57.3% [30.6-74.4] and 60.7 [33.8-77.5], respectively). Adverse event rates in women and infants were similar among groups. Pain at the injection site was more common in women given quadrivalent meningococcal vaccine than in those given trivalent inactivated influenza vaccine (n=253 vs n=132; p<0.0001), although 354 [92%] reactions were mild. Obstetrical and non-obstetrical serious adverse events were reported in 60 (3%) women in the quadrivalent meningococcal vaccine group and 61 (3%) women in the trivalent inactivated influenza vaccine group. Presumed neonatal infection was more common in infants in the trivalent inactivated influenza vaccine group than in those in the quadrivalent meningococcal vaccine group (n=60 vs n=37; p=0.02). No serious adverse events were related to vaccination. INTERPRETATION: Vaccination of pregnant women with trivalent inactivated influenza vaccine in Mali-a poorly resourced country with high infant mortality-was technically and logistically feasible and protected infants from laboratory-confirmed influenza for 4 months. With adequate financing to procure the vaccine, implementation will parallel the access to antenatal care and immunisation coverage of pregnant women with tetanus toxoid. FUNDING: Bill & Melinda Gates Foundation. PMID- 27261070 TI - Metabotropic glutamate receptor 1 promotes cementoblast proliferation via MAP kinase signaling pathways. AB - PURPOSE/AIM: Glutamate is one of the signaling molecules responsible for transmission in the central nervous system. Periodontal ligament (PDL) cells were recently reported to express metabotropic glutamate receptors (mGluRs). However, the functions of mGluR signaling in PDL cells or PDL-related cells remain largely unknown. The aim of this study was to investigate the expression and function of mGluRs in PDL-related cells. MATERIALS AND METHODS: OCCM-30 cells, immortalized murine cementoblasts, were stimulated with l-glutamate or mGluRs antagonists. The cells' proliferative response was evaluated using a colorimetric assay and gene expression was assessed using real-time polymerase chain reaction. The nuclear translocation of cyclin D1 was evaluated by immunohistochemistry. RESULTS: l Glutamate promoted the proliferation of OCCM-30 cells, which expressed mGluR1, but not mGluR5. Dihydroxyphenylglycine (DHPG), an agonist of group I mGluRs (mGluR1 and mGluR5), also promoted cell proliferation, and this was inhibited by LY456236, an mGluR1 antagonist. DHPG increased the expression of cyclin D1, a key regulator of cell proliferation, and its nuclear translocation. DHPG also increased the expression of Bcl2A1, an antiapoptotic oncogene and simultaneously reduced the expression of Bax, a pro-apoptotic marker. Furthermore, the DHPG induced proliferation of OCCM-30 cells was reduced by pretreatment with SB203580, SP600125, and PD98059, inhibitors of p38, JNK, and ERK1/2, respectively. CONCLUSIONS: These findings indicate that activation of mGluR1 expressed by OCCM 30 cells induces cell proliferation in a manner that is dependent on mitogen activated protein kinase pathways and that cyclin D1 and Bcl2A1/Bax may be involved. Our results provide useful information for elucidating the mechanisms underlying cementum homeostasis and regeneration. PMID- 27261071 TI - Ejectable loop recorders? PMID- 27261073 TI - Perioperative echocardiographic assessment of mitral valve regurgitation: a comprehensive review. AB - Cardiac ultrasound allows comprehensive analysis of the complex structure of the mitral valve. Transoesophageal echocardiography is the preferred diagnostic and monitoring technique both in the intraoperative phase and in the immediate postoperative phase. Besides two-dimensional imaging, the 3D approach offers clear advantages in visualizing different aspects of pathology and facilitating interpretation of pathophysiological features. This review comprehensively summarizes anatomical and physiological characteristics, the value of 2D imaging in diagnosis and follow-up and the supplementary significance of 3D echocardiography. PMID- 27261072 TI - Rabbit models to study atherosclerosis and its complications - Transgenic vascular protein expression in vivo. AB - Animal models of atherosclerosis often present limitations of transferability, since important hallmarks of human disease are not completely reproduced in other species. Rabbits have been used in several approaches: 1) inbred strains: Watanabe hereditary hyperlipidemic animals which express a defect in the LDL receptor, 2) transgenic rabbits, which overexpress human lipoproteins, and first knock-out rabbits. 3) native New Zealand white rabbits (NZW) fed with cholesterol rich diet for at least 8 weeks represent the quickest way to establish arteriosclerosis. Rabbits are arguably the most sensitive animal species to cholesterol overload. Interventions in native or arteriosclerotic arteries are used to induce local thrombus formation, e.g. endothelial denudation or photochemical injury. In contrast to smaller animals, catheterisation of coronary arteries is feasible, whose external ligation serves to induce myocardial infarction. As biological endpoints, arterial vasoreactivity/endothelial dysfunction can be studied in analogy to measurements of brachial artery vasomotion in humans in response to increasing doses of acetylcholine or volume challenges. Tissue fixation allows studying vascular morphology, plaque sizes and thrombi after local interventions. Macrophage and T lymphocyte invasion can be investigated histologically. Positron emission tomography (PET/MRI) offers to measure plaques and content in vivo serially in the same animals. Local virally mediated gene transfer to atherosclerotic rabbit arteries has been established as a rapid and reproducible method to test interesting transgenes. Histological plaque features correspond well to alterations in patients (inflammation and lipid load). Thus, effects of any proteins can be studied directly in the arteriosclerotic disease background - much quicker than after germline transgenesis and cross-breeding. PMID- 27261074 TI - The angiotensin II type 1 receptor blocker losartan attenuates bioprosthetic valve leaflet calcification in a rabbit intravascular implant model. AB - OBJECTIVES: There is evidence that angiotensin II type I receptor blocker (ARB) could reduce structural valve deterioration. However, the anticalcification effect on the bioprosthetic heart valve (BHV) has not been investigated. Thus, we investigated the effects of losartan (an ARB) on calcification of implanted bovine pericardial tissue in a rabbit intravascular implant model. METHODS: A total of 16 male New Zealand White rabbits (20 weeks old, 2.98-3.34 kg) were used in this study. Commercially available BHV leaflet of bovine pericardium was trimmed to the shape of a 3-mm triangle and implanted to both external jugular veins of the rabbit. The ARB group (n = 8) was given 25 mg/kg of powdered losartan daily until 6 weeks after surgery by direct administration in the buccal pouch of the animals. The control group (n = 8) was given 5 ml of normal saline by the same method. After 6 weeks, quantitative calcium determination, histological evaluation and western blot analysis of interleukin-6 (IL-6), osteopontin and bone morphogenetic protein 2 (BMP-2) were performed to investigate the mechanisms of the anticalcification effect of losartan. RESULTS: No deaths or complications such as infection or haematoma were recorded during the experiment. All animals were euthanized on the planned date. The calcium measurement level in the ARB group (2.28 +/- 0.65 mg/g) was significantly lower than that in the control group (3.68 +/- 1.00 mg/g) (P = 0.0092). Immunohistochemistry analyses revealed that BMP-2-positive reactions were significantly attenuated in the ARB group. Western blot analysis showed that losartan suppressed the expression of IL-6, osteopontin and BMP-2. CONCLUSIONS: Our results indicate that losartan significantly attenuates postimplant degenerative calcification of a bovine pericardial bioprosthesis in a rabbit intravascular implant model. Further studies are required to assess the effects of ARBs on BHV tissue in orthotopic implantations using a large animal model. PMID- 27261075 TI - Growth and pectus excavatum: is there a relation? PMID- 27261076 TI - Missed diagnosis of atresia of the right pulmonary artery in woman with left sided pneumothorax. AB - Isolated pulmonary atresia is an uncommon condition, which can go undiagnosed for a long time in asymptomatic patients. Sometimes, diagnosis can be made at pregnancy due to respiratory symptoms. There is no known increased risk of pneumothorax. We here present a case where a second-time pregnant woman with an unknown atresia of the right pulmonary artery received a left-sided pneumothorax. The diagnosis was initially missed in spite of adequate imaging and the condition progressed to respiratory stop. We describe the course of diagnostics and the chosen strategy of treatment. PMID- 27261077 TI - A matched pairs analysis of non-rib-spreading, fully endoscopic, mini-incision technique versus conventional mini-thoracotomy for mitral valve repair. AB - OBJECTIVES: Advances in video-assistance lead to an increase in minimal access mitral valve surgery (MAMVS) with decreased incision size yet maintaining the same quality of surgery. Further reduction in surgical trauma and at the same time improved visual guidance can be achieved by a non-rib-spreading fully 3D endoscopic technique (NRS-3D). We compared patients who underwent MAMVS either through an NRS fully 3D endoscopic or rib-spreading (RS) access in a retrospective matched-pair analysis. METHODS: A matched pairs analysis was undertaken of retrospectively collected data of 284 consecutive patients having received an MAMVS between January 2011 and May 2015. Fifty patients with an RS procedure were compared with 50 patients with an NRS fully 3D endoscopic operation. For all patients, access was made through a 3-4 cm incision in the inframammary fold through the fourth intercostal space. In the NRS-3D group, only a soft-tissue protector, and no additional rib-spreader, was used. Operative visualization was provided by 3D endoscopy in the NRS-3D group. RESULTS: The NRS as well as the RS procedure was successful in all patients without technical repair limitations. Mortality was 0% in both groups. Significant differences were seen for operation times (39.0 min mean shorter operation time in the NRS-3D group; P < 0.001), and length of stay on intensive care unit (1.0 day mean shorter stay in the NRS-3D group; P = 0.002) and in the hospital (1.4 days mean shorter stay in the NRS-3D group; P = 0.003). Postoperative analgesics doses were significantly lower in the NRS-3D group [P = 0.007 (paracetamol); P = 0.123 (metamizole); P = 0.013 (piritramide)]. Postoperative pain rated on a pain-scale from 0 to 10 was significantly lower in the NRS-3D group (mean difference of 1.8; P = 0.006). Patient satisfaction regarding cosmetic results was comparable in both the groups. Repair results, ejection fraction, perioperative morbidity and MACCE during follow-up showed no significant differences between both groups. Early postoperative and follow-up echocardiography showed sufficient repair in all patients of both groups with no case of >mild recurrent mitral regurgitation. CONCLUSIONS: An endoscopic procedure supported by 3D-visualization enables superior depth perception, facilitating an excellent quality of repair results. 3D-visualization is a helpful tool especially for complex reconstruction cases and exact placement of artificial neochordae. With this, an experienced mitral valve surgeon takes shorter operation times. Patients benefit from shorter hospitalization with reduced postoperative pain and early mobilization. PMID- 27261078 TI - Preserved brain morphology after controlled automated reperfusion of the whole body following normothermic circulatory arrest time of up to 20 minutes. AB - OBJECTIVES: Clinical outcomes following cardiac arrest (CA) and resuscitation remain a cause for concern. The use of Controlled Automated Reperfusion of the whoLe body (CARL) confers superior neurological outcome even after extended periods of CA. We aimed at investigating clinical outcome and brain morphology preservation when employing CARL following CA periods of 20 min. METHODS: Twenty eight pigs were allocated to four extracorporeal circulation treatment strategies; seven others served as magnetic resonance imaging (MRI) controls. In prompt cardiopulmonary resuscitation (CPR; n = 6), induced circulatory arrest was followed immediately by open cardiac massage of 15 min, thereafter by CARL for 60 min. In delayed CPR (n = 6), induced CA was maintained for 15 min, after that open cardiac massage of 10 min duration was performed prior to extracorporeal CPR (ECPR) of 60 min. Induced CA times of 15 min in the ECPR 15' group (n = 6) and CA of 20 min in the CARL 20' group (n = 10) were followed by ECPR of 60 min and CARL of 60 min, respectively, without prior CPR. Daily neurological deficit scoring (NDS) up to the seventh day, markers of cellular injury [alanine transaminase (ALT), aspartate transaminase (AST) and neuron-specific enolase (NSE)] and brain MRI were performed. RESULTS: 100% survival and normal NDSs were achieved in all animals in the prompt CPR and ECPR 15' groups. In CARL 20', nine animals survived. In contrast, only one animal in the delayed CPR group survived; three animals died within 24 h with a further two dying on Days 4 and 5, respectively. All markers of cellular injury were elevated in the delayed CPR group, ALT [38 (20.3) to 206 U/l (158.2); P = 0.0095], AST [26 (18.8) to 97 U/l (1965.8); P = 0.0095] and NSE [0.45 (0.25) to 7.95 ug/l (24.03); P = 0.0095]. In the ECPR 15' group, only NSE [0.45 (0.15) to 1.20 ug/l (2.40); P = 0.0065] remained elevated. In the CARL 20' group, differences in ALT [36 (10) to 53 U/l (20); P = 0.0005] and NSE [0.50 (0.40) to 1.5 ug/l (0.40); P < 0.0001] values were evident. T2 weighted MR images of the cerebellum [454 (28) to 495 mm2/s (55); U = 11; P = 0.0311], caudate nucleus [400 (59) to 467 mm2/s (42); U = 9; P = 0.0156], lentiform nucleus [377 (89) to 416 mm2/s (55); U = 11; P = 0.0311] and hippocampus [421 (109) to 511 mm2/s (58); U = 9; P = 0.0164] in the CARL 20' group showed higher signal intensities compared with controls. In delayed CPR, corresponding regions of interest on early apparent diffusion coefficient images showed a restricted diffusion. CONCLUSIONS: In our experimental animal model of CA, CARL results in satisfactory survival at CA periods of 20 min despite detected enzyme and morphological changes. These changes did not translate to clinical neurological deficits. PMID- 27261079 TI - Two-stage free anterolateral thigh flap in the management of full-thickness chest wall resection. AB - Free tissue transfers are sometimes required in the reconstruction of large full thickness chest wall defects. To minimize the risk of viscera exposure in case of free flap complications, we describe a two-stage procedure using an anterolateral thigh flap. PMID- 27261080 TI - Assessing pruritus as a quality of life metric in the teledermatology setting. PMID- 27261081 TI - Diversity and divergence of the glioma-infiltrating T-cell receptor repertoire. AB - Although immune signaling has emerged as a defining feature of the glioma microenvironment, how the underlying structure of the glioma-infiltrating T-cell population differs from that of the blood from which it originates has been difficult to measure directly in patients. High-throughput sequencing of T-cell receptor (TCR) repertoires (TCRseq) provides a population-wide statistical description of how T cells respond to disease. We have defined immunophenotypes of whole repertoires based on TCRseq of the alpha- and beta-chains from glioma tissue, nonneoplastic brain tissue, and peripheral blood from patients. Using information theory, we partitioned the diversity of these TCR repertoires into that from the distribution of VJ cassette combinations and diversity due to VJ independent factors, such as selection due to antigen binding. Tumor-infiltrating lymphocytes (TILs) possessed higher VJ-independent diversity than nonneoplastic tissue, stratifying patients according to tumor grade. We found that the VJ independent components of tumor-associated repertoires diverge more from their corresponding peripheral repertoires than T-cell populations in nonneoplastic brain tissue, particularly for low-grade gliomas. Finally, we identified a "signature" set of TCRs whose use in peripheral blood is associated with patients exhibiting low TIL divergence and is depleted in patients with highly divergent TIL repertoires. This signature is detectable in peripheral blood, and therefore accessible noninvasively. We anticipate that these immunophenotypes will be foundational to monitoring and predicting response to antiglioma vaccines and immunotherapy. PMID- 27261083 TI - Long-Term Survival After Off-Pump Coronary Artery Bypass Grafting. AB - BACKGROUND: The aim of this study was to compare the long-term survival rates of patients undergoing isolated first-time coronary artery bypass grafting (CABG) by off-pump CABG with the long-term survival rates in patients undergoing CABG using cardioplegic cardiopulmonary bypass techniques. METHODS: All patients undergoing isolated CABG at a single center (Manchester Heart Centre, Manchester, United Kingdom) between 2000 and 2014 were included. Propensity score matching was performed on the basis of on demographic variables. The in-hospital morbidity and long-term all-cause mortality rates for matched patients were compared. RESULTS: A total of 8,055 patients were identified, with a median follow-up of 7.0 years. With patients matched for preoperative patient characteristics, there was no significant difference in long-term survival between cardiopulmonary bypass and off-pump CABG (n = 2,082 each; 11.5 years vs 11.3 years; p = 0.178). In the off pump CABG group, there were significantly fewer in-hospital cerebrovascular complications (0.5% vs 1.1%; p = 0.017), and mean length of stay was shorter (7.6 days vs 8.1 days; p < 0.0001). Arterial conduit use was significantly higher in the off-pump group, with more right mammary artery grafts (16.3% vs 4.3%; p < 0.0001) and sequential grafts (27.1% vs 13.5%; p < 0.0001). The mean number of grafts was higher in the on-pump group (3.28 +/- 0.94 vs 3.10 +/- 1.10; p < 0.0001). CONCLUSIONS: Long-term survival after off-pump CABG is not inferior to long-term survival after on-pump CABG despite a lower mean number of grafts. A statistically significant difference in cerebrovascular complications may be related to conduit choice and reduced aortic manipulation. PMID- 27261082 TI - A Preoperative Risk Model for Postoperative Pneumonia After Coronary Artery Bypass Grafting. AB - BACKGROUND: Postoperative pneumonia is the most prevalent of all hospital acquired infections after isolated coronary artery bypass graft surgery (CABG). Accurate prediction of a patient's risk of this morbid complication is hindered by its low relative incidence. In an effort to support clinical decision making and quality improvement, we developed a preoperative prediction model for postoperative pneumonia after CABG. METHODS: We undertook an observational study of 16,084 patients undergoing CABG between the third quarter of 2011 and the second quarter of 2014 across 33 institutions participating in the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. Variables related to patient demographics, medical history, admission status, comorbid disease, cardiac anatomy, and the institution performing the procedure were investigated. Logistic regression through forward stepwise selection (p < 0.05 threshold) was utilized to develop a risk prediction model for estimating the occurrence of pneumonia. Traditional methods were used to assess the model's performance. RESULTS: Postoperative pneumonia occurred in 3.30% of patients. Multivariable analysis identified 17 preoperative factors, including demographics, laboratory values, comorbid disease, pulmonary and cardiac function, and operative status. The final model significantly predicted the occurrence of pneumonia, and performed well (C-statistic: 0.74). These findings were confirmed through sensitivity analyses by center and clinically important subgroups. CONCLUSIONS: We identified 17 readily obtainable preoperative variables associated with postoperative pneumonia. This model may be used to provide individualized risk estimation and to identify opportunities to reduce a patient's preoperative risk of pneumonia through prehabilitation. PMID- 27261084 TI - Randomized Study of a New Noninvasive Skin Closure Device for Use After Congenital Heart Operations. AB - BACKGROUND: We report a new, noninvasive Zip surgical skin closure device (ZipLine Medical, Campbell, CA). This device is considered to have good cosmetic outcomes after operations and reduces surgical time. In this study, skin closure using the Zip device was compared with subcuticular sutures and the usefulness and safety of this new device was evaluated. METHODS: This was a prospective, randomized study of 214 patients who underwent cardiac operations through a median sternotomy from June 2014 to December 2015. In 136 patients, this was a first operation group of which 71 patients underwent Zip surgical skin closure (Zip group), and 65 patients underwent subcuticular sutures (suture group). In 78 patients, this was a reoperation group, of which 42 patients were in the Zip group and 36 patients were in the suture group. Cosmetic results using the Vancouver Scar Scale were evaluated separately in the first operation group and reoperation group. RESULTS: There were significant differences in the total Vancouver Scar Scale score between the first operation group (p < 0.001) and reoperation group (p = 0.007). The skin closure time was significantly shorter in the Zip group than in the suture group (113.0 +/- 9.1 seconds vs 375.9 +/- 60.2 seconds, p < 0.001). No significant differences were found regarding the rate of surgical site infection between the groups. Complications peculiar to this device included skin discoloration (0.9%), epidermolysis (0.9%), and exfoliation of the device (1.8%); however, no serious complications developed. CONCLUSIONS: In congenital heart operations through a median sternotomy, the Zip surgical skin closure device was an excellent choice for improving the cosmetic appearance and reducing the wound closure time. In addition, it proved to be a device that could be used safely. PMID- 27261085 TI - At the Root of the Repair Debate: Outcomes After Elective Aortic Root Replacements for Aortic Insufficiency With Aneurysm. AB - BACKGROUND: There is growing interest in aortic valve-sparing and valve repair operations, but the ideal operation and timing of intervention in these generally younger patients undergoing operations for aortic insufficiency (AI) and dilated ascending aorta remains controversial. METHODS: Root replacements at a single institution from 2002 to 2014 were reviewed. Inclusion criteria were age younger than 70 and presence of moderate or greater aortic insufficiency (AI), with or without aortic aneurysm. Of 1,425 root replacements, 220 patients were considered in the final analysis. RESULTS: Moderate AI was present in 87 patients and severe AI in 133 patients. The 30-day mortality was 0% in moderate AI patients and 2% (n = 3) in severe AI patients (p = 0.3). Freedom from reoperation was 95% at 10 years. Severe preoperative AI was associated with worse long-term survival compared with moderate AI (hazard ratio, 2.6; p = 0.04). Patients undergoing root replacement with moderate AI had similar survival compared with the age- and gender-matched United States population (log-rank p = 0.93), whereas patients with severe AI had significantly worse survival (log-rank p = 0.02). Other multivariable predictors of decreased long-term survival were age (hazard ratio, 1.1; p = 0.01) and preoperative renal failure (hazard ratio, 6.9; p < 0.01). CONCLUSIONS: Elective root replacement operations in patients younger than 70 are associated with low rates of mortality and reoperation, which should be considered the benchmark operation for aortic valve-sparing or repair operations in similar patients. Worse survival was associated with severe AI and older age, suggesting earlier intervention may be an appropriate therapeutic strategy in selected patients. PMID- 27261086 TI - Bicuspid Aortic Insufficiency With Aortic Root Aneurysm: Root Reimplantation Versus Bentall Root Replacement. AB - BACKGROUND: In patients with a bicuspid aortic valve presenting with aortic insufficiency (AI) and root aneurysm, we assessed whether outcomes with primary cusp repair with root reimplantation were equivalent to the gold standard Bentall procedures. METHODS: From 2002 to 2014, 710 patients with bicuspid aortic valve underwent aortic root procedures. Of these, only patients presenting with noncalcified type I bicuspid aortic valve with AI (n = 165) were included to maintain anatomic and physiologic homogeneity between the groups. Aortic stenosis, endocarditis, redo root, and emergency cases were excluded. Patients undergoing valve-sparing root reimplantation (VSRR group, n = 45) were retrospectively compared with those undergoing Bentall root replacement (Bentall group, n = 120). RESULTS: Patients in the Bentall group were older (52 +/- 13 vs 46 +/- 12 years; p <= 0.01) and had a lower ejection fraction (0.53 +/- 0.12 versus 0.58 +/- 0.08; p < 0.01), but left ventricular diastolic diameter was similar (58 +/- 10 mm versus 57 +/- 9 mm; p = 0.5). Thirty-day and in-hospital mortality was zero; in-hospital stroke rate was 0.8% (n = 1) in the Bentall group (0 in the VSRR group; p = 0.54). Permanent pacemaker rate was 6% (n = 7) in the Bentall group (0 in the VSRR group; p = 0.2). On discharge echocardiography, AI grade <= 1+ (100%; p = 1) and transvalvular gradients (mean gradient 7 +/- 3 versus 6 +/- 3 mm Hg; p = 0.14) were similar. Mean follow-up was 7.5 +/- 3.2 and 3.4 +/- 2.9 years (p < 0.001). There were 14 transient ischemic attacks or stroke events in the Bentall group, and none in the VSRR group. One patient in each group exhibited AI >= 3+. Five-year actuarial survival (100% versus 98% +/- 2%; p = 0.8) and freedom from aortic reoperation (98% +/- 2% versus 100%; p = 0.8) were similar. CONCLUSIONS: In patients with bicuspid aortic valve AI with root aneurysm, primary cusp repair with root reimplantation achieves equivalent midterm outcomes compared with Bentall root replacement. PMID- 27261088 TI - Cannabinoid receptor-2 stimulation suppresses neuroinflammation by regulating microglial M1/M2 polarization through the cAMP/PKA pathway in an experimental GMH rat model. AB - Excessive inflammatory responses are involved in secondary brain injury during germinal matrix hemorrhage (GMH). The process of microglial polarization to the pro-inflammatory M1 or anti-inflammatory M2 phenotypes is considered to occur in a major immunomodulatory manner during brain inflammation. We previously found that cannabinoid receptor-2 (CB2R) stimulation attenuated microglial accumulation and brain injury following experimental GMH. However, whether CB2R has effects on microglial polarization after GMH remains unclear. Herein, we investigated the effects of CB2R stimulation on neuroinflammation after experimental GMH and the potential mechanisms that mediate M1/M2 microglial phenotype regulation. The results indicated that during the GMH acute phase, microglia primarily polarized to the M1 phenotype and induced an overwhelming release of pro-inflammatory cytokines. However, JWH133, a selective CB2R agonist, significantly prevented the pro-inflammatory cytokine release while promoting an M1 to M2 phenotype transformation in microglia, resulting in an increased anti-inflammatory cytokine release. Moreover, in thrombin-induced rat primary microglial cells, JWH133 reduced the pro-inflammatory cytokine levels and M1 phenotype by enhancing the acquisition of the M2 phenotype. Additionally, JWH133 facilitated synthesis of cyclic AMP (cAMP) and its downstream effectors, phosphorylated cAMP-dependent protein kinase (p-PKA) and exchange protein activated by cyclic-AMP 1 (Epac1). The promoting effects of JWH133 on M2 polarization were attenuated with a specific PKA inhibitor but not with an Epac inhibitor, indicating that the cAMP/PKA signaling pathway was involved in the JWH133 effects. This is the first study to propose that promotion of microglial M2 polarization through the cAMP/PKA pathway participates in the CB2R-mediated anti-inflammatory effects after GMH induction. The results will help to further understand the mechanisms that underlie neuroprotection by CB2R in GMH and promote clinical translational research for CB2R agonists. PMID- 27261087 TI - RubisCO selection using the vigorously aerobic and metabolically versatile bacterium Ralstonia eutropha. AB - Recapturing atmospheric CO2 is key to reducing global warming and increasing biological carbon availability. Ralstonia eutropha is a biotechnologically useful aerobic bacterium that uses the Calvin-Benson-Bassham (CBB) cycle and the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) for CO2 utilization, suggesting that it may be a useful host to bioselect RubisCO molecules with improved CO2 -capture capabilities. A host strain of R. eutropha was constructed for this purpose after deleting endogenous genes encoding two related RubisCOs. This strain could be complemented for CO2 -dependent growth by introducing native or heterologous RubisCO genes. Mutagenesis and suppressor selection identified amino acid substitutions in a hydrophobic region that specifically influences RubisCO's interaction with its substrates, particularly O2 , which competes with CO2 at the active site. Unlike most RubisCOs, the R. eutropha enzyme has evolved to retain optimal CO2 -fixation rates in a fast-growing host, despite the presence of high levels of competing O2 . Yet its structure-function properties resemble those of several commonly found RubisCOs, including the higher plant enzymes, allowing strategies to engineer analogous enzymes. Because R. eutropha can be cultured rapidly under harsh environmental conditions (e.g., with toxic industrial flue gas), in the presence of near saturation levels of oxygen, artificial selection and directed evolution studies in this organism could potentially impact efforts toward improving RubisCO-dependent biological CO2 utilization in aerobic environments. ENZYMES: d-ribulose 1,5-bisphosphate carboxylase/oxygenase, EC 4.1.1.39; phosphoribulokinase, EC 2.7.1.19. PMID- 27261089 TI - GPs' experiences with enhanced collaboration between psychiatry and general practice for children with ADHD. AB - BACKGROUND: Most general practitioners (GPs) do not feel comfortable with diagnosing and treating children with attention deficit hyperactivity disorder (ADHD). This is problematic since ADHD is a prevalent disorder and an active role of GPs is desired. In the Netherlands a collaborative ADHD programme was established, comprising of shortened diagnostic assessment in specialized mental healthcare followed by psycho-education in mental healthcare and pharmacological treatment by pre-trained GPs. OBJECTIVES: To explore the experiences of GPs regarding the diagnosis and treatment of children with uncomplicated ADHD within this programme. METHODS: Semi-structured interviews with 15 GPs were conducted. The GPs participated in an evaluation of the collaborative ADHD programme. Data was analysed using the principles of constant comparative analysis. RESULTS: Most participating GPs expressed reluctance to diagnose ADHD themselves. The reluctance was due to a lack of time, knowledge and experience. The GPs welcomed the collaborative programme because it met their need for both quick and adequate diagnosis by a specialist. Furthermore, an online ADHD course, offered by the programme, gave them the confidence to start and monitor ADHD medication. Finally, they appreciated the possibility of consulting a specialist when necessary. CONCLUSION: GPs preferred that ADHD was diagnosed by a specialist. In the context of the ADHD collaborative programme, they felt competent and comfortable to start and monitor medication in children with uncomplicated ADHD. Key Messages Within a collaborative ADHD programme for children, participating GPs were positive about a quick and specialist diagnostic process within secondary care. After an online course, GPs felt confident to start and monitor ADHD medication in children with uncomplicated ADHD. GPs were content about the collaboration between primary and secondary care. PMID- 27261090 TI - Mitogen-activated protein kinases as key players in osmotic stress signaling. AB - BACKGROUND: Osmotic stress arises from the difference between intracellular and extracellular osmolality. It induces cell swelling or shrinkage as a consequence of water influx or efflux, which threatens cellular activities. Mitogen-activated protein kinases (MAPKs) play central roles in signaling pathways in osmotic stress responses, including the regulation of intracellular levels of inorganic ions and organic osmolytes. SCOPE OF REVIEW: The present review summarizes the cellular osmotic stress response and the function and regulation of the vertebrate MAPK signaling pathways involved. We also describe recent findings regarding apoptosis signal-regulating kinase 3 (ASK3), a MAP3K member, to demonstrate its regulatory effects on signaling molecules beyond MAPKs. MAJOR CONCLUSIONS: MAPKs are rapidly activated by osmotic stress and have diverse roles, such as cell volume regulation, gene expression, and cell survival/death. There is significant cell type specificity in the function and regulation of MAPKs. Based on its activity change during osmotic stress and its regulation of the WNK1-SPAK/OSR1 pathway, ASK3 is expected to play important roles in osmosensing mechanisms and cellular functions related to osmoregulation. GENERAL SIGNIFICANCE: MAPKs are essential for various cellular responses to osmotic stress; thus, the identification of the upstream regulators of MAPK pathways will provide valuable clues regarding the cellular osmosensing mechanism, which remains elusive in mammals. The elucidation of in vivo MAPK functions is also important because osmotic stress in physiological and pathophysiological conditions often results from changes in the intracellular osmolality. These studies potentially contribute to the establishment of therapeutic strategies against diseases that accompany osmotic perturbation. PMID- 27261091 TI - A paler shade of green? The toxicology of biodiesel emissions: Recent findings from studies with this alternative fuel. AB - BACKGROUND: Biodiesel produced primarily from plants and algal feedstocks is believed to have advantages for production and use compared to petroleum and to some other fuel sources. There is some speculation that exposure to biodiesel combustion emissions may not induce biological responses or health effects or at a minimum reduce the effects relative to other fuels. In evaluating the overall environmental and health effects of biodiesel production to end use scenario, empirical data or modeling data based on such data are needed. SCOPE OF REVIEW: This manuscript examines the available toxicology reports examining combustion derived biodiesel emissions since approximately 2007, when our last review of the topic occurred. Toxicity derived from other end uses of biodiesel - e.g., spills, dermal absorption, etc. - are not examined. Findings from biodiesel emissions are roughly divided into three areas: whole non-human animal model exposures; in vitro exposures of mammalian and bacterial cells (used for mutation studies primarily); and human exposures in controlled or other exposure fashions. MAJOR CONCLUSIONS: Overall, these more current studies clearly demonstrate that biodiesel combustion emission exposure- to either 100% biodiesel or a blend in petroleum diesel- can induce biological effects. There are reports that show biodiesel exposure generally induces more effects or a greater magnitude of effect than petroleum diesel, however there are also a similar number of reports showing the opposite trend. It is unclear whether effects induced by exposure to a blend are greater than exposure to 100% biodiesel. Taken together, the evidence suggest biodiesel emissions can have some similar effects as diesel emissions on inflammatory, vascular, mutagenic, and other responses. GENERAL SIGNIFICANCE: While acute biodiesel exposures can show toxicity with a variety of endpoints, the potential effects on human health need further validation. Additionally there are few or no findings to date on whether biodiesel emissions can induce effects or even a weaker response that petroleum diesel with repeated exposure scenarios such as in an occupational setting. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. PMID- 27261093 TI - Augmentation and impulsive behaviors in restless legs syndrome: Coexistence or association? AB - OBJECTIVES: To assess the frequency of impulse control disorders (ICDs) in patients with restless legs syndrome (RLS) with and without augmentation under dopaminergic therapy in a case-control study. Augmentation and ICDs are both serious complications of dopaminergic treatment of RLS but little is known about possible associations between these drug-induced disorders. METHODS: In total, 58 patients with idiopathic RLS diagnosed according to the International Restless Legs Syndrome Study Group criteria were recruited. Of these, 35 patients had augmentation. The frequency of ICD symptoms was assessed using semi-structural interviews. RESULTS: Demographic variables did not differ between patients with RLS with and without augmentation but those with augmentation took higher dopaminergic medication than patients without augmentation. Twenty-three patients with RLS (39.7%) had ICD symptoms, with 12 patients (20.7%) having definitive ICDs. Patients with augmentation had an increased risk of expressing ICD symptoms (p = 0.007, odds ratio 5.64, 95% confidence interval 1.59-20.02). CONCLUSIONS: Patients with RLS with augmentation have an almost 6-fold increased risk of exhibiting ICD symptoms. This implies that augmentation and ICDs are related and may share a common pathophysiology. Moreover, our results have clinical implications, suggesting that patients with RLS with augmentation should be screened for ICD symptoms. PMID- 27261094 TI - Augmentation and impulsivity in restless legs syndrome patients: A complex interaction. PMID- 27261092 TI - Gamma-irradiation produces active chlorine species (ACS) in physiological solutions: Secoisolariciresinol diglucoside (SDG) scavenges ACS - A novel mechanism of DNA radioprotection. AB - BACKGROUND: Secoisolariciresinol diglucoside (SDG), the main lignan in whole grain flaxseed, is a potent antioxidant and free radical scavenger with known radioprotective properties. However, the exact mechanism of SDG radioprotection is not well understood. The current study identified a novel mechanism of DNA radioprotection by SDG in physiological solutions by scavenging active chlorine species (ACS) and reducing chlorinated nucleobases. METHODS: The ACS scavenging activity of SDG was determined using two highly specific fluoroprobes: hypochlorite-specific 3'-(p-aminophenyl) fluorescein (APF) and hydroxyl radical sensitive 3'-(p-hydroxyphenyl) fluorescein (HPF). Dopamine, an SDG structural analog, was used for proton (1)H NMR studies to trap primary ACS radicals. Taurine N-chlorination was determined to demonstrate radiation-induced generation of hypochlorite, a secondary ACS. DNA protection was assessed by determining the extent of DNA fragmentation and plasmid DNA relaxation following exposure to ClO( ) and radiation. Purine base chlorination by ClO(-) and gamma-radiation was determined by using 2-aminopurine (2-AP), a fluorescent analog of 6-aminopurine. RESULTS: Chloride anions (Cl(-)) consumed >90% of hydroxyl radicals in physiological solutions produced by gamma-radiation resulting in ACS formation, which was detected by (1)H NMR. Importantly, SDG scavenged hypochlorite- and gamma-radiation-induced ACS. In addition, SDG blunted ACS-induced fragmentation of calf thymus DNA and plasmid DNA relaxation. SDG treatment before or after ACS exposure decreased the ClO(-) or gamma-radiation-induced chlorination of 2-AP. Exposure to gamma-radiation resulted in increased taurine chlorination, indicative of ClO(-) generation. NMR studies revealed formation of primary ACS radicals (chlorine atoms (Cl) and dichloro radical anions (Cl2-)), which were trapped by SDG and its structural analog dopamine. CONCLUSION: We demonstrate that gamma-radiation induces the generation of ACS in physiological solutions. SDG treatment scavenged ACS and prevented ACS-induced DNA damage and chlorination of 2-aminopurine. This study identified a novel and unique mechanism of SDG radioprotection, through ACS scavenging, and supports the potential usefulness of SDG as a radioprotector and mitigator for radiation exposure as part of cancer therapy or accidental exposure. PMID- 27261095 TI - Gallbladder and the risk of polyps and carcinoma in metachromatic leukodystrophy. AB - OBJECTIVES: To assess frequency of gallbladder polyposis and carcinoma in metachromatic leukodystrophy (MLD). METHODS: We evaluated 34 patients with MLD (average age 16.7 years, age range 2-39 years) screened for gallbladder abnormalities by ultrasound. In the case of cholecystectomy, findings at pathology were reviewed. RESULTS: Only 8 of 34 patients (23%) had a normal gallbladder at ultrasound. Gallbladder polyps were visible in 8 patients (23%). Cholecystectomy was performed in 11 patients (32%). In these, pathology revealed various abnormalities, including hyperplastic polyps, intestinal metaplasia, prominent Rokitansky-Aschoff sinuses, and sulfatide storage. CONCLUSIONS: Our results demonstrate that gallbladder involvement is the rule rather than the exception in MLD. The high prevalence of hyperplastic polyps, a known precancerous condition, and one death from gallbladder carcinoma at a young age suggest that MLD predisposes to neoplastic gallbladder abnormalities. As novel therapies for this patient group are emerging leading to increased life expectancy, we recommend screening for gallbladder abnormalities by ultrasound in order to prevent early death. PMID- 27261096 TI - Assessing the Relationship of Mammographic Breast Density and Proliferative Breast Disease. AB - Increased breast density and a history of benign breast biopsy are both considered risk factors for developing breast cancer. Understanding the specifics of these risk factors and their relationship to each other can lead to a better understanding of a patient's propensity for breast cancer development and improved surveillance strategies. We included 245 women who underwent a benign breast biopsy without atypia between October 2011 and June 2013. Biopsies were performed for suspicious calcifications as well as masses and architectural distortion. Lesions biopsied were divided into two groups: calcified and noncalcified lesions. The patient's breast density was assessed on most recent mammogram and was classified using the American College of Radiology BI-RADS density categories. Based on histologic diagnosis, each case was classified as proliferative or nonproliferative breast disease. The median age of the cohort (n = 245) was 55 years (range, 40-84 years). There were 162 (66%) postmenopausal women in the study. A core biopsy was performed for calcifications in 33.5% cases and for noncalcified lesions in 58% cases. In patients with dense breast tissue, an underlying proliferative histology was found significantly more frequently with calcifications (66.7%) as opposed to noncalcified lesions (35.9%) (RR = 2.3 (1.3-4.0); chi(2) = 8.7; p = 0.003). In nondense breast patients, there was no significant difference (RR = 1.1 (0.7-1.8); chi(2) = 0.1; p = 0.738). In the postmenopausal group, women with dense breasts had proliferative histology significantly more frequently than women with nondense breasts (55.3% versus 38.3%; p < 0.05), regardless of the underlying lesion type. Postmenopausal women with dense breasts who underwent a breast biopsy with benign histology had a significantly higher likelihood of having proliferative breast disease, regardless of underlying lesion type. Women with dense breasts also showed proliferative histology significantly more often for calcifications as opposed to noncalcified lesions. PMID- 27261097 TI - Corona discharges with water electrospray for Escherichia coli biofilm eradication on a surface. AB - Low-temperature plasma (cold), a new method for the decontamination of surfaces, can be an advantageous alternative to the traditional chemical methods, autoclave or dry heat. Positive and negative corona discharges in air were tested for the eradication of 48-h Escherichia coli biofilms grown on glass slides. The biofilms were treated by cold corona discharge plasma for various exposure times. Water electrospray from the high voltage electrode was applied in some experiments. Thermostatic cultivation of the biofilm, and confocal laser scanning microscopy (CLSM) of the biofilm stained with fluorescent dyes were used for biocidal efficiency quantification. Up to 5 log10 reduction of bacterial concentration in the biofilm was measured by thermostatic cultivation after exposure to both corona discharges for 15min. This decontamination efficiency was significantly enhanced by simultaneous water electrospray through the plasma. CLSM showed that the live/dead ratio after treatment remained almost constant inside the biofilm; only cells on the top layers of the biofilm were affected. DAPI fluorescence showed that biofilm thickness was reduced by about 1/3 upon exposure to the corona discharges with electrospray for 15min. The biofilm biomass loss by about 2/3 was confirmed by crystal violet assay. PMID- 27261098 TI - Targeted genetics in Drosophila cell lines: Inserting single transgenes in vitro. AB - A long-standing problem with analyzing transgene expression in tissue-culture cells is the variation caused by random integration of different copy numbers of transfected transgenes. In mammalian cells, single transgenes can be inserted by homologous recombination but this process is inefficient in Drosophila cells. To tackle this problem, our group, and the Cherbas group, used recombination mediated cassette exchange (RMCE) to introduce single-copy transgenes into specific locations in the Drosophila genome. In both cases, phiC31 was used to catalyze recombination between its target sequences attP in the genome, and attB flanking the donor sequence. We generated cell lines de novo with a single attP flanked cassette for recombination, whereas, Cherbas et al. introduced a single attP-flanked cassette into existing cell lines. In both approaches, a 2-drug selection scheme was used to select for cells with a single copy of the donor sequence inserted by RMCE and against cells with random integration of multiple copies. Here we describe the general advantages of using RMCE to introduce genes into fly cells, the different attributes of the 2 methods, and how future work could make use of other recombinases and CRISPR/Cas9 genome editing to further enable genetic manipulation of Drosophila cells in vitro. PMID- 27261100 TI - 2016 Wellcome Image Awards, across the UK and beyond. PMID- 27261099 TI - Effects of postnatal bromocriptine injection on thyroid function and prolactinemia of rats at adulthood. AB - Previously, we demonstrated that maternal prolactin inhibition at the end of lactation, using bromocriptine (BRO), leads to an increase in leptin transfer via milk and induces the adult progeny to present hypothyroidism, leptin resistance and metabolic syndrome (obesity, hyperglycemia, hypertriglyceridemia, lower HDL). To test if these alterations are due to direct BRO action on the pups, in the present study we evaluated the long-term effects of direct injection of BRO (0.1MUg/once daily) in male Wistar rats from postnatal (PN) day 1 to 10 (early treatment) or from PN11 to 20 (late treatment) on: food intake, body mass, cardiovascular parameters, hormone profile, hypothalamic leptin signaling, glucose homeostasis and thyroid hormone-dependent proteins. The respective controls were injected with methanol-saline. Offspring were killed at adulthood (PN180). Adult PN1-10 BRO-treated animals had lower food intake, hypoprolactinemia, lower leptin action (lower OBR-b, STAT-3 and SOCS-3 mRNA levels in the arcuate nucleus), lower TRH-TSH-thyroid axis as well as lower thyroid hormone markers. On the other hand, adult animals that were BRO-treated during the PN11-20 period showed hyperphagia, higher blood pressure, higher prolactinemia and OBR-b, higher TRH and plasma T3, hypercorticosteronemia as well as higher Dio2 and UCP1 mRNA expression in the brown adipose tissue. Glucose homeostasis was not changed treatment in either period. Our data show that early and late dopamine overexposure during lactation induces diverse metabolic disturbances later in life, increasing the risk of thyroid dysfunction and, consequently, changes in prolactinemia. PMID- 27261101 TI - Outcomes of spontaneous bacterial peritonitis in liver transplant recipients with allograft failure. AB - BACKGROUND: Spontaneous bacterial peritonitis (SBP) carries appreciable morbidity and mortality in the pre-liver transplant (LT) setting. However, the occurrence of SBP and its consequences in the post-LT setting have not been well characterized. METHODS: This is a retrospective study of SBP occurring in post-LT patients between January 2007 and December 2012. Outcomes were compared to a cohort of post-LT patients with allograft failure and ascites without SBP. RESULTS: The most common indication for liver transplantation in this cohort was hepatitis C. A total of 29 episodes of SBP in 21 patients were identified. Escherichia coli (19%) and Klebsiella pneumoniae (10%) were the most frequent pathogens identified. Six patients died during their first episode of SBP. Ten patients were eventually listed for liver re-transplantation (re-LT) after their first episode of SBP; 5 of these patients were transplanted and the other 5 died. Of the 5 who were transplanted, 2 died shortly after re-transplant, and 3 are still alive. The cause of death in the majority of patients was infection (83.3%). The median time from onset of ascites to death was 214 days (range: 10 1085 days) and from the first episode of SBP to death was 50.5 days (range: 4-549 days). In contrast, the median time from onset of ascites to death in patients with allograft failure and ascites without SBP was 331.5 days (45-2400 days). CONCLUSIONS: Allograft failure with ascites is a poor prognostic factor and these patients should be considered high risk for re-LT. SBP may accelerate the time to mortality. PMID- 27261102 TI - Bifunctional role of pro-inflammatory cytokines after traumatic brain injury. AB - BACKGROUND: Pro-inflammatory cytokines play an essential role in maintenance of normal brain function as well as in repair after traumatic brain injuries (TBI). However, massive and uncontrolled release of these cytokines, particularly interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha, can also result in a great deal of additional brain damage. Levels of these cytokines may increase in the brain thousands of times more than do the corresponding levels in serum. RESEARCH DESIGN: Narrative literature review. Outcome and conclusions: Strategies to control the levels of these pro-inflammatory cytokines and to reduce the cytokine-induced brain damage are discussed. There is extensive evidence from experiments in animal models that suppression of cytokines is effective in ameliorating neurologic damage after TBI. However, the efficacy of this approach remains to be proven in patient trials. PMID- 27261103 TI - Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations. AB - Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5 - 15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3 months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted. PMID- 27261153 TI - Restricted ADP movement in cardiomyocytes: Cytosolic diffusion obstacles are complemented with a small number of open mitochondrial voltage-dependent anion channels. AB - Adequate intracellular energy transfer is crucial for proper cardiac function. In energy starved failing hearts, partial restoration of energy transfer can rescue mechanical performance. There are two types of diffusion obstacles that interfere with energy transfer from mitochondria to ATPases: mitochondrial outer membrane (MOM) with voltage-dependent anion channel (VDAC) permeable to small hydrophilic molecules and cytoplasmatic diffusion barriers grouping ATP-producers and consumers. So far, there is no method developed to clearly distinguish the contributions of cytoplasmatic barriers and MOM to the overall diffusion restriction. Furthermore, the number of open VDACs in vivo remains unknown. The aim of this work was to establish the partitioning of intracellular diffusion obstacles in cardiomyocytes. We studied the response of mitochondrial oxidative phosphorylation of permeabilized rat cardiomyocytes to changes in extracellular ADP by recording 3D image stacks of NADH autofluorescence. Using cell-specific mathematical models, we determined the permeability of MOM and cytoplasmatic barriers. We found that only ~2% of VDACs are accessible to cytosolic ADP and cytoplasmatic diffusion barriers reduce the apparent diffusion coefficient by 6 10*. In cardiomyocytes, diffusion barriers in the cytoplasm and by the MOM restrict ADP/ATP diffusion to similar extents suggesting a major role of both barriers in energy transfer and other intracellular processes. PMID- 27261154 TI - Primary care physicians' perspectives on the prescription opioid epidemic. AB - BACKGROUND: Prescription opioid use disorder and overdose have risen substantially in the U.S. Primary care physicians are critical to many ongoing and proposed efforts to address the prescription opioid epidemic. Yet, little is known about their attitudes and beliefs surrounding this issue. This study aimed to determine primary care physicians' perceptions of the seriousness of the problem, its causes, groups responsible for addressing it, attitudes toward individuals with prescription opioid use disorder, beliefs about the effectiveness of addiction treatments, and support for various policies. METHODS: We conducted a national web-based survey in 2014 among 1010 primary care physicians. We gauged responses to attitude and belief items on 7-point Likert scales. We examined the proportion agreeing with each statement, and whether responses differed among physicians prescribing higher and lower volumes of opioids. RESULTS: Respondents largely attributed the causes of prescription opioid use disorder to individual-oriented factors and certain physician-oriented factors, and believed that individuals with prescription opioid use disorder and physicians were primarily responsible for addressing the problem. Negative attitudes toward people with prescription opioid use disorder were prevalent, but a majority believed that treatment could be effective. There was majority support for all measured policies, with the highest levels of support for policies to monitor prescribing among patients potentially at risk for an opioid use disorder and to improve physician education and training. CONCLUSIONS: Given strong endorsement of recommended policies, physician support could be leveraged to advance efforts to curb prescription opioid use disorder and overdose. PMID- 27261155 TI - Survalytics: An Open-Source Cloud-Integrated Experience Sampling, Survey, and Analytics and Metadata Collection Module for Android Operating System Apps. AB - BACKGROUND: We describe here Survalytics, a software module designed to address two broad areas of need. The first area is in the domain of surveys and app analytics: developers of mobile apps in both academic and commercial environments require information about their users, as well as how the apps are being used, to understand who their users are and how to optimally approach app development. The second area of need is in the field of ecological momentary assessment, also referred to as experience sampling: researchers in a wide variety of fields, spanning from the social sciences to psychology to clinical medicine, would like to be able to capture daily or even more frequent data from research subjects while in their natural environment. OBJECTIVE: Survalytics is an open-source solution for the collection of survey responses as well as arbitrary analytic metadata from users of Android operating system apps. METHODS: Surveys may be administered in any combination of one-time questions and ongoing questions. The module may be deployed as a stand-alone app for experience sampling purposes or as an add-on to existing apps. The module takes advantage of free-tier NoSQL cloud database management offered by the Amazon Web Services DynamoDB platform to package a secure, flexible, extensible data collection module. DynamoDB is capable of Health Insurance Portability and Accountability Act compliant storage of personal health information. RESULTS: The provided example app may be used without modification for a basic experience sampling project, and we provide example questions for daily collection of blood glucose data from study subjects. CONCLUSIONS: The module will help researchers in a wide variety of fields rapidly develop tailor-made Android apps for a variety of data collection purposes. PMID- 27261156 TI - Neurochemistry of lead and manganese. PMID- 27261157 TI - Military suicide coverage: AP news wire & suicide guidelines. AB - The authors evaluated how well Associated Press News Wire stories adhered to the Recommendations for Reporting on SuicideTM during 2012, a peak year of military suicide. They included individual suicide stories (N = 167) from randomly selected days. They also evaluated differences in the military versus civilian coverage. Military and civilian stories typically had about five negative practices, and less than one positive practice, with military stories significantly more likely to miss valuable opportunities to promote help-seeking. The findings, combined with previous evidence, suggest the need for the development of specific military suicide reporting guidelines. PMID- 27261158 TI - Reliable individual-level neural markers of high-level language processing: A necessary precursor for relating neural variability to behavioral and genetic variability. AB - The majority of functional neuroimaging investigations aim to characterize an average human brain. However, another important goal of cognitive neuroscience is to understand the ways in which individuals differ from one another and the significance of these differences. This latter goal is given special weight by the recent reconceptualization of neurological disorders where sharp boundaries are no longer drawn either between health and neuropsychiatric and neurodevelopmental disorders, or among different disorders (e.g., Insel et al., 2010). Consequently, even the variability in the healthy population can inform our understanding of brain disorders. However, because the use of functional neural markers is still in its infancy, no consensus presently exists about which measures (e.g., effect size?, extent of activation?, degree of lateralization?) are the best ones to use. We here attempt to address this question with respect to one large-scale neural system: the set of brain regions in the frontal and temporal cortices that jointly support high-level linguistic processing (e.g., Binder et al., 1997; Fedorenko, Hsieh, Nieto-Castanon, Whitfield-Gabrieli, & Kanwisher, 2010). In particular, using data from 150 individuals all of whom had performed a language "localizer" task contrasting sentences and nonword sequences (Fedorenko et al., 2010), we: a) characterize the distributions of the values for four key neural measures of language activity (region effect sizes, region volumes, lateralization based on effect sizes, and lateralization based on volumes); b) test the reliability of these measures in a subset of 32 individuals who were scanned across two sessions; c) evaluate the relationship among the different regions of the language system; and d) evaluate the relationship among the different neural measures. Based on our results, we provide some recommendations for future studies of brain-behavior and brain-genes relationships. Although some of our conclusions are specific to the language system, others (e.g., the fact that effect-size-based measures tend to be more reliable than volume-based measures) are likely to generalize to the rest of the brain. PMID- 27261159 TI - Perceptual demand and distraction interactions mediated by task-control networks. AB - Modulation of selective attention appears to be under the guidance of a cluster of distinct task-control networks, the frontroparietal (FPN) and cingulo opercular (CON). Yet, their role in mediating the relationship between task perceptual load and presence/absence of distraction in the auditory modality is unclear. Here, we examined this interaction using functional magnetic resonance imaging (fMRI) and an auditory signal detection task. The auditory stimulus signal-to-noise ratio (SNR) was parametrically manipulated, by varying the amplitude of the Tone while holding the Noise constant, to create four perceptual load conditions presented in combination with or without acoustic distraction. Regions of the FPN (e.g., dorsolateral prefrontal cortex, inferior parietal lobule) and CON (e.g., dorsal anterior cingulate cortex/medial superior frontal cortex, anterior prefrontal cortex, anterior insula/frontal operculum) were modulated by perceptual load and distraction, such that lower loads induced a pattern of increased activity when there was no distraction. On the other hand, a trend of augmented activity was found in higher loads during distraction. These findings suggest a role for the FPN and CON in mediating the allocation of attentional resources to competing auditory information under varying degrees of perceptual demand. PMID- 27261161 TI - Uncertainty and expectancy deviations require cortico-subcortical cooperation. AB - In a dynamic and uncertain environment it is beneficial to learn the causal structure of the environment in order to minimize uncertainty. This requires determining estimates of probable outcomes, which will guide expectations about incoming information. One key factor in this learning process is to detect whether an unexpected event constitutes a low probability, but valid outcome, or an outright error. The present 7T-fMRI study investigated the role of subcortical structures in regulating this probabilistic inferential learning process. A new task was designed, in which participants learned to calculate the value, and therefore to anticipate the outcome of different visual sequences. Three types of sequences provided unambiguous, ambiguous, and incongruent contextual evidence and each sequence had two outcomes, which differed in their probability of occurrence. We hypothesized that subcortical regions are necessary when expectations are violated, and that their involvement will depend on the nature of the unexpected event. The results show increased dorsomedial striatal and thalamic activation for less probable sequences; in addition, ambiguous sequences also display larger activation in the red nuclei. Incongruent sequences displayed a pattern of subcortical activation restricted to the dorsolateral and the posterior dorsomedial striatum. These results confirm that different subcortical structures regulate uncertainty and expectancy deviations; this is crucial not only for learning to predict events in the environment, but also for flexible cognitive control in general. PMID- 27261160 TI - Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults. AB - The ability to regulate emotion is crucial to promote well-being. Evidence suggests that the medial prefrontal cortex (mPFC) and adjacent anterior cingulate (ACC) modulate amygdala activity during emotion regulation. Yet less is known about whether the amygdala-mPFC circuit is linked with regulation of the autonomic nervous system and whether the relationship differs across the adult lifespan. The current study tested the hypothesis that heart rate variability (HRV) reflects the strength of mPFC-amygdala interaction across younger and older adults. We recorded participants' heart rates at baseline and examined whether baseline HRV was associated with amygdala-mPFC functional connectivity during rest. We found that higher HRV was associated with stronger functional connectivity between the amygdala and the mPFC during rest across younger and older adults. In addition to this age-invariant pattern, there was an age-related change, such that greater HRV was linked with stronger functional connectivity between amygdala and ventrolateral PFC (vlPFC) in younger than in older adults. These results are in line with past evidence that vlPFC is involved in emotion regulation especially in younger adults. Taken together, our results support the neurovisceral integration model and suggest that higher heart rate variability is associated with neural mechanisms that support successful emotional regulation across the adult lifespan. PMID- 27261162 TI - Detection of functional brain network reconfiguration during task-driven cognitive states. AB - Network science offers computational tools to elucidate the complex patterns of interactions evident in neuroimaging data. Recently, these tools have been used to detect dynamic changes in network connectivity that may occur at short time scales. The dynamics of fMRI connectivity, and how they differ across time scales, are far from understood. A simple way to interrogate dynamics at different time scales is to alter the size of the time window used to extract sequential (or rolling) measures of functional connectivity. Here, in n=82 participants performing three distinct cognitive visual tasks in recognition memory and strategic attention, we subdivided regional BOLD time series into variable sized time windows and determined the impact of time window size on observed dynamics. Specifically, we applied a multilayer community detection algorithm to identify temporal communities and we calculated network flexibility to quantify changes in these communities over time. Within our frequency band of interest, large and small windows were associated with a narrow range of network flexibility values across the brain, while medium time windows were associated with a broad range of network flexibility values. Using medium time windows of size 75-100s, we uncovered brain regions with low flexibility (considered core regions, and observed in visual and attention areas) and brain regions with high flexibility (considered periphery regions, and observed in subcortical and temporal lobe regions) via comparison to appropriate dynamic network null models. Generally, this work demonstrates the impact of time window length on observed network dynamics during task performance, offering pragmatic considerations in the choice of time window in dynamic network analysis. More broadly, this work reveals organizational principles of brain functional connectivity that are not accessible with static network approaches. PMID- 27261163 TI - Improved multi-shot diffusion imaging using GRAPPA with a compact kernel. AB - In multi-shot diffusion imaging, motion induced phase variations are traditionally seen as a source of artifacts and corrected in the image domain using SENSE-based methods. This correction usually requires image echo and navigator echo to be geometrically matched. Recently, a k-space based method, realigned GRAPPA, has been proposed. It realigns data from different shots into the same k-space locations, and then synthesizes the missing data using GRAPPA algorithm. In this study, we refined the theory for GRAPPA-based method. In the revised theory, phase variations are treated as a kind of encoding, similar to coil sensitivity encoding. Based on this, the missing data can be synthesized using k-space correlations among different shots and channels. Then a compact kernel is used which only includes acquired data with significant contribution for the data synthesis, and can generate accurate weights without strict navigator size requirements. Simulation studies as well as brain and cervical spine experiments demonstrate that the proposed reconstruction method can effectively suppress artifacts caused by phase variations, and provide diffusion images with high resolution and low distortion. Compared with SENSE-based methods, the proposed method is less sensitive to mismatch between image echo and navigator echo. PMID- 27261164 TI - Piezoelectric surgery and navigation: a safe approach for complex cases of Eagle syndrome. AB - Eagle syndrome was first described by Eagle in 1937. It is associated with an elongated styloid process and/or calcification of the stylohyoid ligament, mainly resulting in pain in the orofacial region. The treatment of Eagle syndrome includes conservative treatment with physical therapy supported by medication, or surgical removal of the styloid process. Two different surgical approaches are described in the literature: the transoral and transcervical approaches. Both have their limitations and specific intraoperative risks. A modification of the transcervical approach that adds an extra security measure to the treatment of complex cases of Eagle syndrome is presented herein. The styloid process was removed by combining piezoelectric surgery, preoperative digital planning, and surgical navigation. No complication was noted, and the patient recovered quickly after surgery. A follow-up visit 2 months later showed no remaining symptoms of Eagle syndrome on the treated side. Therefore, digital planning and surgical navigation could add valuable safety measures to the treatment of complex cases of Eagle syndrome. PMID- 27261165 TI - The bony cartilaginous unit: the missing graft in septorhinoplasty. AB - To achieve the desired nasoseptal refinements in septorhinoplasty, sufficient septal cartilage is needed. There are many cases in which septal cartilage is insufficient, especially in revision surgery. To obtain an optimal outcome, a bony cartilaginous unit is proposed as a versatile graft for various parts of the nose. This bony cartilaginous unit is extracted using the open septorhinoplasty approach in which the bilateral septal flaps are elevated over the entire cartilaginous and bony part; however, the cartilaginous septum and posterior bony part are not separated and are removed as an integrated unit. These bony cartilaginous units can be used as various types of grafts at different sites in the nose. In the present study, the bony cartilaginous units were used as caudal extension grafts, spreader grafts, lateral crural strut grafts, and for the closure of septal perforations. This research has shown the advantage of using septal bone in conjunction with cartilage as an integrated unit to correct external nose and septal deformities, especially in cartilage-depleted patients. PMID- 27261166 TI - 3-O-Laurylglyceryl ascorbate reinforces skin barrier function through not only the reduction of oxidative stress but also the activation of ceramide synthesis. AB - OBJECTIVE: A higher trans-epidermal water loss (TEWL) occurs in rough skin, in elder skin and also in atopic dermatitis. An impaired skin barrier function is considered to be caused by an incomplete construction of the intercellular lamellar structure due to the quantitative reduction of ceramides. Since these symptoms coexist with oxidative stress, we hypothesized that impairment of the skin barrier function is accelerated by oxidative stress. Thus, the purpose of this study was to clarify the effect of oxidative stress on ceramide synthesis and to characterize whether antioxidants can improve skin barrier function. 3-O Laurylglyceryl ascorbate (VC-3LG), which is a newly amphipathic derivative of ascorbic acid, was evaluated as a candidate antioxidant. METHODS: We characterized the mRNA expression levels of serine palmitoyltransferase (SPT) in normal human epidermal keratinocytes (NHEKs) treated with H2 O2 using real-time PCR analysis. In order to evaluate the effect of VC-3LG on skin barrier function, we used several assays with reconstructed human epidermis equivalents (RHEEs). RESULTS: Ceramide synthesis was down-regulated in NHEKs by oxidative stress. Treatment with VC-3LG abrogated the down-regulation of SPT mRNA in NHEKs caused by oxidative stress, and stimulated SPT mRNA expression levels. In experiments characterizing the antioxidative properties of VC-3LG, VC-3LG reduced oxidative stress in NHEKs by up-regulating catalase mRNA expression. In addition, VC-3LG stimulated the skin barrier function in RHEEs, which had lower TEWL values compared with untreated RHEEs. Furthermore, VC-3LG increased the quantity of ceramide in RHEEs. CONCLUSION: Taken together, we conclude that VC-3LG reinforces the skin barrier function due to its reduction of oxidative stress and its promotion of ceramide synthesis. PMID- 27261167 TI - Inactivation of Listeria monocytogenes ATCC 7644 on fresh-cut tomato using nisin in combinations with organic salts. AB - The inhibition of Listeria monocytogenes ATCC 7644 on fresh-cut tomato was investigated using nisin alone, and in combinations with organic salts. Nisin at a concentration of 5000UI/mL was introduced alone or in combination with an organic salt (sodium citrate or sodium acetate each at 3 and 5g/100mL each) on fresh-cut tomato previously inoculated with 10(8)CFU/mL of L. monocytogenes ATCC 7644. Chlorine at 200ppm was used as a control. The inoculated samples were incubated at different temperatures (4, 10 and 25 degrees C) and examined at 0, 24, 48 and 72h. The effects of the antimicrobial treatments on quality parameters of tomato (pH, soluble solids, titratable acidity and vitamin C) were also evaluated, and colour parameters were observed at the lowest storage temperature for 10 days. Both nisin and the organic salts inhibited growth of L. monocytogenes, but the combinations of two compounds were more effective. The nisin-sodium citrate (5%) combination was significantly (p<=0.05) effective, while chlorine was least effective against L. monocytogenes. The quality parameters were substantially retained, especially at 4 degrees C, suggesting good shelf stability at a low temperature. These results substantiate the use of the cheap and eco-friendly approach to reducing this pathogen of health concern in common fresh produce. PMID- 27261168 TI - Laryngeal Electromyographic findings in patients with vocal fold motion asymmetry. AB - OBJECTIVES/HYPOTHESIS: Vocal fold motion asymmetry (VFMA) is often attributed to vocal fold paresis or an anatomical variant. Although laryngeal electromyography (LEMG) may be used to evaluate patients with vocal fold paresis, electrodiagnostic findings in VFMA have not been well defined. STUDY DESIGN: Review of a case series METHODS: Twenty-five symptomatic patients with VFMA were examined by LEMG, and the findings were analyzed. RESULTS: Although all were thought to have unilateral recurrent laryngeal nerve paresis, LEMG showed only nine to have unilateral recurrent nerve paresis. There were nine with both ipsilateral recurrent laryngeal nerve and superior laryngeal nerve paresis, four with bilateral paresis, and three were normal. Reduced total number of units, reduced recruitment, motor units firing fast, and polyphasic units were more common, whereas fibrillation potentials, fasciculation, positive sharp waves, and complex repetitive discharges were uncommon. The LEMG findings are most consistent with old, healed neuropathy. McNemar's test for the acute versus chronic denervation potentials showed significant differences. CONCLUSIONS: VFMA has a high incidence of vocal fold paresis that can be better defined by LEMG. The site and side of paresis is often wrong based on laryngoscopy findings alone. The LEMG findings of VFMA appear to be consistent with old, healed neuropathy LEVEL OF EVIDENCE: 4 Laryngoscope, 126:E273-E277, 2016. PMID- 27261169 TI - Porcine epidemic diarrhea in China. AB - Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by Porcine epidemic diarrhea virus (PEDV) that characterized by vomiting, diarrhea, and dehydration. PEDV was first identified in the 1980s in China, and since then, it has become one of the most common viral causes of diarrhea. In October 2010, a large-scale outbreak of PED caused by a PEDV variant occurred in China, resulting in tremendous economic losses. This review presents a comprehensive description of PEDV history, prevalence, molecular features, and prevention and control strategies in China. PMID- 27261170 TI - Impact of aerobic exercise training during chemotherapy on cancer related cognitive impairments in patients suffering from acute myeloid leukemia or myelodysplastic syndrome - Study protocol of a randomized placebo-controlled trial. AB - Cancer related cognitive impairments (CRCI) are frequently reported by patients prior to, during and after medical treatment. Although this cognitive decline severely affects patients' quality of life, little is known about effective treatments. Exercise programs represent a promising supportive strategy in this field. However, evidence is sparse and existing studies display methodological limitations. In the planned study, 83 men and women newly diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will be randomized into one of three treatment groups. During 4weeks of induction chemotherapy with Anthracycline and Cytarabin patients allocated to exercise group will cycle 3*/week for 30min at moderate to vigorous intensity on an ergometer. Patients allocated to placebo group will receive a supervised myofascial release training (3*/week, approx. 30min) and patients at control group will get usual care. As primary endpoints a cognitive test battery will be conducted measuring performances depending on verbal/spatial memory and executive functioning. Secondary endpoints will be self-perceived cognitive functioning, as well as neurotrophic and inflammatory serum markers. All assessments will be conducted immediately after hospitalization and before chemotherapy is commenced, immediately before discharge of hospital after 4-5weeks as well as before continuing medical treatment 3-4weeks after discharge. This will be the first study investigating the impact of an aerobic exercise training on CRCI in AML/MDS patients. We hope that the study design and the state-of-the-art assessments will help to increase knowledge about CRCI in general and exercise as potential treatment option in this under investigated population. PMID- 27261171 TI - A cybercycling intervention to improve behavioral regulation and classroom functioning among children with behavioral health disorders: Pragmatic randomized trial design for Manville Moves. AB - While positive and clinically meaningful effects of exercise on cognition and behavior in children have been demonstrated in controlled experimental settings, they have rarely been translated and rigorously evaluated in real-world environments. In particular, there is a lack of research on school-based approaches to sustainable physical activity and exercise interventions targeting children with behavioral health disorders. Manville Moves is an exercise intervention designed to improve behavioral regulation and classroom functioning among children with neurodevelopmental and affective disorders within a therapeutic day-school environment. The curriculum is built around virtual reality exergaming bicycles (cybercycles) and integrated into physical education (PE) classes. Manville Moves was developed using community based participatory research (CBPR) and implemented as a pragmatic trial. In this paper, we describe (a) the background, theoretical framework and intervention setting, (b) the Manville Moves curriculum, (c) the study design and outcome and process measures, and (d) the strategies used to support implementation compliance and intervention uptake by a population with a variety of behavioral challenges. We conclude with a detailed description of the participatory process by which the intervention was developed and integrated into school programming and a review of the program's key innovations and approaches to addressing threats to internal and external validity. PMID- 27261172 TI - Clinical and molecular heterogeneity of head and neck spindle cell and sclerosing rhabdomyosarcoma. PMID- 27261173 TI - Venous aneurysm of the facial vein that presented as a lump in the neck: a case report. PMID- 27261174 TI - Interdental application of bone reduction forceps: a simple alternative to a bridle wire. PMID- 27261175 TI - Ilko Dacowo: The practice of iatrogenic tooth enucleation. PMID- 27261176 TI - Genome-scale CRISPR pooled screens. AB - Genome editing technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) systems have ushered in a new era of targeted DNA manipulation. The easy programmability of CRISPR using short oligonucleotides enables rapid synthesis of large-scale libraries for functional genetic screens. Here we present fundamental concepts and methods for pooled CRISPR screens and review biological results from recent genome-scale loss-of-function and gain-of function screens. We also discuss new frontiers in pooled screens, including novel effector domains for functional screens and applications in the noncoding genome. PMID- 27261177 TI - 3-O-Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells. AB - Eight 3-O-alkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin through two synthetic approaches. A one-pot reaction, starting with aerobic oxidation of silibinin followed by direct alkylation of the phenolic hydroxyl group in the subsequent 2,3-dehydrosilibinin, furnishes the desired derivatives in 11-16% yields. The three-step procedure employing benzyl ether to protect 7-OH in silibinin generates the desired derivatives in 30-46% overall yields. The antiproliferative activity of the 2,3-dehydrosilibinin derivatives against both androgen-sensitive and androgen-insensitive prostate cancer cells have been assessed using a WST-1 cell proliferation assay. All derivatives exhibited greater antiproliferative potency than silibinin, with 2,3 dehydrosilibinins each possessing a three- to five-carbon linear alkyl group to 3 OH (IC50 values in a range of 1.71-3.06MUM against PC-3 and LNCaP cells) as the optimal derivatives. The optimal potency was reached with three- to five-carbon alkyl groups. Our findings suggest that 3-O-propyl-2,3-dehydrosilibinin effectively inhibits the growth of PC-3 prostate cancer cells by arresting cell cycle in the G0/G1 phase, but not by activating PC-3 cell apoptosis. PMID- 27261178 TI - Novel JAK1-selective benzimidazole inhibitors with enhanced membrane permeability. AB - The previously identified Janus kinase 1 (JAK1)-selective inhibitor, 1-(2 aminoethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole-5-carboxamide (2), suffered from low cell permeability, which resulted in poor pharmacokinetic properties. In this study, by introducing less polar hydrogen bond donors at N(1) (a hydroxyalkyl or a methylaminoalkyl group) and C2 (a cyclohexanol group) positions, a series of novel benzimidazole derivatives were prepared, which exhibited selective JAK1 inhibitory activity (IC50 against JAK1=0.08-0.15MUM; JAK1-selectivity=26-40 fold vs JAK2, 12-23 fold vs JAK3, and 38-54 fold vs Tyk2) along with significantly increased lipophilicity (3.3-15.8 times) as well as membrane permeability (6.3-12 times). PMID- 27261179 TI - Identification of potent and selective retinoic acid receptor gamma (RARgamma) antagonists for the treatment of osteoarthritis pain using structure based drug design. AB - A series of triaryl pyrazoles were identified as potent pan antagonists for the retinoic acid receptors (RARs) alpha, beta and gamma. X-ray crystallography and structure-based drug design were used to improve selectivity for RARgamma by targeting residue differences in the ligand binding pockets of these receptors. This resulted in the discovery of novel antagonists which maintained RARgamma potency but were greater than 500-fold selective versus RARalpha and RARbeta. The potent and selective RARgamma antagonist LY2955303 demonstrated good pharmacokinetic properties and was efficacious in the MIA model of osteoarthritis like joint pain. This compound demonstrated an improved margin to RARalpha mediated adverse effects. PMID- 27261180 TI - Synthesis and in vitro evaluation of hydrazinyl phthalazines against malaria parasite, Plasmodium falciparum. AB - In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum. Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. These results indicate the potential of hydralazine derivatives as reference scaffolds to develop novel antimalarials. PMID- 27261181 TI - New halogenated tris-(phenylalkyl)amines as h5-HT2B receptor ligands. AB - A series of compounds in which various halogen substituents were incorporated into a phenyl ring of a tris-(phenylalkyl)amine scaffold, was synthesized and evaluated for affinity to h5-HT2 receptors. In general, all compounds were found to have good affinity for the 5-HT2B receptor and were selective over 5-HT2A and 5-HT2C receptors. Compound 9i was the most selective compound in this study and is the highest affinity 5-HT2B receptor ligand bearing a tris-(phenylalkyl)amine scaffold to date. PMID- 27261182 TI - Urethral Foreign Bodies: Clinical Presentation and Management. AB - OBJECTIVE: To review a single institution's 15-year experience with urethral foreign bodies, including evaluation, clinical findings, and treatment. MATERIALS AND METHODS: In total, 27 patients comprising 35 episodes of inserted urethral foreign bodies were reviewed at Cook County Hospital between 2000 and 2015. Retrospective chart review was performed to describe the clinical presentation, rationale for insertion, management, recidivism, and sequelae. RESULTS: Median patient age was 26 (range 12-60). Twenty-six patients (97 %) were male, 1 was female (3%). Items inserted included pieces of plastic forks, spoons, metal screws and aluminum, pieces of cardboard or paper, staples, writing utensils such as pens and pencils, as well as coaxial cable and spray foam sealant. Reported reasons for insertion were self-stimulation, erectile enhancement, and attention seeking. Presenting symptoms included dysuria, gross hematuria, urinary retention, urinary tract infection, and penile discharge. The most common technique for removal was manual extraction with extrinsic pressure (n = 19, 54%). Other methods include endoscopic retrieval (n = 8, 23%), open cystotomy (n = 1, 3%), and voiding to expel the foreign body (n = 7, 20%). Postremoval complications included urinary tract infection (n = 7), sepsis (n = 4), urethral false passage (n = 5), laceration (n = 5), and stricture (n = 1). CONCLUSION: We present the largest single-institutional series of urethral foreign bodies to date. Urethral foreign body insertion is a relatively rare occurrence and, commonly, is a recurrent behavior. Urethral trauma related to foreign body insertion is associated with significant risk of infection and urethral injury with long-term sequelae. PMID- 27261183 TI - Use of a Non-cross-linked Xenograft (Xenform) in Surgical Treatment of Peyronie's Disease. AB - OBJECTIVE: To evaluate the effectiveness in Peyronie's disease surgical treatment using Xenform, a non-cross-linked graft derived from dermal bovine tissue, to close the defect obtained after plaque incision, without penile prosthesis implant. A further objective is to evaluate the satisfaction of patients. MATERIALS AND METHODS: We treated with plaque incision 28 patients with a stable penile curvature >=60 degrees hindering penetration and with erectile function conserved. International Index of Erectile Function-15 and a not-validated questionnaire constituted of 7 questions about their satisfaction were administered after 1 year of follow-up. Furthermore, specific questions were relative about penile straightening, penile postoperative length, glandular sensitivity, and feeling palpability. RESULTS: Graft is resulted compatible with albugineal features, like thickness, consistency, and elasticity; it is waterproof, allowing the visualization of complete correction of the curvature after the suture. No severe complications were observed except 1 hematoma requiring surgical revision. Sixteen patients were seen after at least 1 year of follow-up. Curvature improvement was obtained in all cases, with the complete straightening in 75%; we did not observe any retraction of the graft and any recurrence on the curvature. Significant reduced glans sensibility and erectile dysfunction were the more frequent postoperative complications, resulting in 43.8% and 25%, respectively. All patients are satisfied with the straightening. Only 2 patients are dissatisfied about the overall result. CONCLUSION: Plaque incision corporoplasty with Xenform graft is an effective and safe surgical treatment. Xenform is a secure and a reliable albugineal substitute, comparable to other heterologous graft. We have not observed any retraction. Patient's satisfaction is linked to the treatment result and to sexual life. PMID- 27261184 TI - Genetic Basis of Posterior Urethral Valves Inheritance. AB - OBJECTIVE: To highlight genetic pattern of posterior urethral valves (PUVs), we performed a genetic study on 2 siblings affected. PUVs are the most common congenital cause of lower urinary tract obstruction and an important cause of renal failure in infants (50% progress to end-stage renal disease in 10 years). PUVs occur in 1 of 5000-8000 male infants, but real incidence is arduous to determine because of the wide spectrum of possible clinical presentation. A different recurrence rate is reported in African Americans and children with Down syndrome, although usually PUVs are not found in syndromic conditions but constitute an isolated disorder. Although most cases appear to be sporadic, some reports in literature suggest a partial genetic etiology. MATERIALS AND METHODS: We report 2 brothers with PUVs. The children's mother was a healthy woman but had a history of urinary tract infections of unknown etiology. We investigated possible familial genetic anomalies using a DNA array comparative genomic hybridization technique. RESULTS: We identified 2 partial duplications in the short arm of chromosome 11 recurring in both children and mother. CONCLUSION: This finding, not previously reported to our knowledge, adds new data to support the hypothesis of the presence of a hereditary component in the occurrences of PUVs. PMID- 27261185 TI - Unexpected High Rates of Angiography and Angioembolization for Isolated Low-grade Renal Trauma: Results From a Large, Statewide, Trauma Database. AB - OBJECTIVE: To evaluate usage of diagnostic angiography (DA) and renal angioembolization (RAE) for isolated renal injuries while assessing differences in utilization based on trauma-level designation. METHODS: Isolated renal injuries from 2000 to 2013 were identified in the prospectively maintained Pennsylvania Trauma Outcome Study database and stratified by the American Association for the Surgery of Trauma kidney injury grade. Therapeutic intervention and International Classification of Diseases-9 codes identified DA and/or RAE performance, whereas renal injury was designated through Abbreviated Injury Scale codes. Univariate and multivariate models identified factors associated with utilization of DA or RAE. RESULTS: Of 449,422 patients entered into the Pennsylvania Trauma Outcome Study from 2000 to 2013, 1628 (0.4%) isolated kidney injuries were identified. The majority of patients (1190/1628, 73.1%) experienced low-grade (American Association for the Surgery of Trauma I III) renal trauma. Although isolated grade IV (41/350, 11.7%) or grade V (10/88, 11.4%) renal trauma patients underwent DA or RAE at a greater rate (P < .001), low-grade patients still underwent DA or RAE 4.3% (51/1190) of the time. Patients with grade I injuries were significantly more likely to undergo DA or RAE at level 1 trauma centers (odds ratio 5.4, 95% confidence interval 1.2-23.8, P = .03). CONCLUSION: Despite overwhelming evidence supporting conservative management for patients with isolated, low-grade traumatic renal injuries, contemporary utilization of DA and RAE in such patients treated at trauma centers is surprisingly high. Factors accounting for a significant increase in utilization at Level 1 trauma centers need to be further elucidated. PMID- 27261186 TI - The impact of long-term secukinumab treatment on Epstein-Barr virus and cytomegalovirus loads in patients with psoriasis. PMID- 27261193 TI - Peroxiredoxin-2 nitrosylation facilitates cardiomyogenesis of mouse embryonic stem cells via XBP-1s/PI3K pathway. AB - Protein nitrosylation is a ubiquitous post-translational modification in almost all biological systems. However, its function on stem cell biology is so far incompletely understood. Here, we demonstrated that peroxiredoxin 2 (Prdx-2) nitrosylation was involved in cardiomyocyte differentiation of mouse embryonic stem (ES) cells induced by S-nitrosoglutathione (GSNO). We found that temporary GSNO exposure could promote ES cell-derived cardiomyogenesis. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics approach, coupled with biotin switch technique, a total of 104 nitrosylated proteins were identified. Specifically, one of the antioxidant enzymes, Prdx-2, was abundantly nitrosylated and temporarily reduced in antioxidant activity, causing transient endogenous hydrogen peroxide (H2O2) accumulation and subsequent X-box binding protein-1s/phosphatidylinositol 3-kinase pathway activation. The present study reveals the mechanism in which GSNO favors cardiomyocyte differentiation. Prdx-2 nitrosylation could be a potent strategy to affect the pluripotent stem cell-derived cardiomyogenesis. PMID- 27261194 TI - Real-time and high-throughput analysis of mitochondrial metabolic states in living cells using genetically encoded NAD+/NADH sensors. AB - Mitochondria are central organelles that regulate cellular bioenergetics, biosynthesis, and signaling processes. NADH, a key player in cell metabolism, is often considered as a marker of mitochondrial function. However, traditional methods for NADH measurements are either destructive or unable to distinguish between NADH and NADPH. In contrast to traditional methods, genetically encoded NADH sensors can be used for the real-time tracking and quantitative measurement of subcellular NADH levels in living cells. Therefore, these sensors provide innovative tools and address the limitations of current techniques. We herein summarize the properties of different types of recently developed NADH biosensors, discuss their advantages and disadvantages, and focus on the high throughput analysis of mitochondrial function by using highly responsive NAD+/NADH sensors. PMID- 27261195 TI - The contribution of Glycobiology to the Zika outbreak in the Americas. PMID- 27261196 TI - Inhibition of hyaluronic acid formation sensitizes chronic myelogenous leukemia to treatment with doxorubicin. AB - In the current study we examined the ability of 4-methylumbelliferone (4-MU), which can inhibit hyaluronic acid synthesis, to sensitize K562 chronic myelogenous leukemia (CML) cells to doxorubicin therapy. Exposure of K562 cells to doxorubicin led to increased hyaluronic acid synthase (HAS) gene expression and increased levels of cell surface hyaluronic acid. Furthermore, exposure of K562 cells to exogenous HA caused resistance to doxorubicin-induced cell death. The combination of low dose 4-MU and doxorubicin led to increased apoptosis when compared to higher doses of any agent alone. Additionally, treatment with 4-MU led to a significant reduction in doxorubicin-induced increase in HA cell surface expression. Mechanistically, 4-MU treatment led to an increase in p38 activation and PARP cleavage. The role of p38 in 4-MU/doxorubicin-treated K562 cells was confirmed when p38 inhibitors led to protection from 4-MU/doxorubicin-induced apoptosis. Together, results from this study suggest that treatment with 4-MU increases the sensitivity of CML to chemotherapeutics by decreasing their HA mediated resistance to apoptosis. PMID- 27261197 TI - Dopamine signaling promotes the xenobiotic stress response and protein homeostasis. AB - Multicellular organisms encounter environmental conditions that adversely affect protein homeostasis (proteostasis), including extreme temperatures, toxins, and pathogens. It is unclear how they use sensory signaling to detect adverse conditions and then activate stress response pathways so as to offset potential damage. Here, we show that dopaminergic mechanosensory neurons in C. elegans release the neurohormone dopamine to promote proteostasis in epithelia. Signaling through the DA receptor DOP-1 activates the expression of xenobiotic stress response genes involved in pathogenic resistance and toxin removal, and these genes are required for the removal of unstable proteins in epithelia. Exposure to a bacterial pathogen (Pseudomonas aeruginosa) results in elevated removal of unstable proteins in epithelia, and this enhancement requires DA signaling. In the absence of DA signaling, nematodes show increased sensitivity to pathogenic bacteria and heat-shock stress. Our results suggest that dopaminergic sensory neurons, in addition to slowing down locomotion upon sensing a potential bacterial feeding source, also signal to frontline epithelia to activate the xenobiotic stress response so as to maintain proteostasis and prepare for possible infection. PMID- 27261199 TI - Is there a role for the use of aviation assessment instruments in surgical training preparation? A feasibility study. AB - BACKGROUND: Selection for surgical residency programmes could potentially be improved through pretraining preparation, after assessment of surgical candidates' sensorimotor skills and personality traits. Existing aviation pilot selection instruments are available to test sensorimotor skills and personality traits. This study examined selected instruments to assess medical trainees' sensorimotor skills and personality traits. METHODS: Aviation's validated computer-based Computerized Pilot Aptitude and Screening System (COMPASS) and Checklist Professional Profile (CPP) were applied to 166 final year medical students during a surgical clerkship between 2013 and 2015. RESULTS: All trainees completed COMPASS and CPP within the prescribed 2 hours. Compared with an age matched and gender-matched cohort of 165 pilot candidates, medical trainees scored significantly higher on eye-hand coordination (p<0.001), need for variation (p<0.001), empathy (p=0.006), helpfulness (p<0.001) and autonomy (p<0.001). Pilot candidates scored higher on eye-hand-foot coordination (p<0.001), spatial orientation (p<0.001), persuasiveness (p<0.001), stress tolerance (p<0.001), dominance (p<0.001), ambition (p<0.001) and resilience (p<0.001). CONCLUSIONS: Final year medical trainees from one medical school were able to complete aviation's sensorimotor skills and personality traits selection instruments within the set time frame. They scored differently from aviation trainees on selected skills and personality traits. The applicability and utility of aviation instruments to presurgical training preparation remains to be tested. PMID- 27261200 TI - Rapidly progressive dementia and unilateral jerky movements: a case of Creutzfeldt-Jakob disease. PMID- 27261198 TI - DnaJ/Hsc70 chaperone complexes control the extracellular release of neurodegenerative-associated proteins. AB - It is now known that proteins associated with neurodegenerative disease can spread throughout the brain in a prionlike manner. However, the mechanisms regulating the trans-synaptic spread propagation, including the neuronal release of these proteins, remain unknown. The interaction of neurodegenerative disease associated proteins with the molecular chaperone Hsc70 is well known, and we hypothesized that much like disaggregation, refolding, degradation, and even normal function, Hsc70 may dictate the extracellular fate of these proteins. Here, we show that several proteins, including TDP-43, alpha-synuclein, and the microtubule-associated protein tau, can be driven out of the cell by an Hsc70 co chaperone, DnaJC5. In fact, DnaJC5 overexpression induced tau release in cells, neurons, and brain tissue, but only when activity of the chaperone Hsc70 was intact and when tau was able to associate with this chaperone. Moreover, release of tau from neurons was reduced in mice lacking the DnaJC5 gene and when the complement of DnaJs in the cell was altered. These results demonstrate that the dynamics of DnaJ/Hsc70 complexes are critically involved in the release of neurodegenerative disease proteins. PMID- 27261201 TI - Shear stress-induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible. AB - AIM: Is modulation of skeletal muscle capillary supply by altering blood flow due to a presumptive shear stress response per se, or dependent on the vasodilator mechanism? METHODS: The response to four different vasodilators, and cotreatment with blockers of NO and prostaglandin synthesis, was compared. Femoral artery blood flow was correlated with capillary-to-fibre ratio (C:F) and protein levels of putative angiogenic compounds. RESULTS: All vasodilators induced a similar increase in blood flow after 14 days, with a similar effect on C:F (1.62 +/- 0.05, 1.60 +/- 0.01, 1.57 +/- 0.06, 1.57 +/- 0.07, respectively, all P < 0.05 vs. control 1.20 +/- 0.01). Concomitant inhibitors revealed differential effects on blood flow and angiogenesis, demonstrating that a similar response may have different signalling origins. The time course of this response with the most commonly used vasodilator, prazosin, showed that blood flow increased from 0.40 mL min-1 to 0.61 mL min-1 by 28 days (P < 0.05), dropped within 1 week after the cessation of treatment (0.54 mL min-1 ; P < 0.05) and returned to control levels by 6 weeks. In parallel with FBF, capillary rarefaction began within 1 week (P < 0.05), giving C:F values similar to control by 2 weeks. Of the dominant signalling pathways, prazosin decreased muscle VEGF, but increased its cognate receptor Flk-1 (both P < 0.01); levels of eNOS varied with blood flow (P < 0.05), and Ang-1 initially increased, while its receptor Tie-2 was unchanged, with only modest changes in the antiangiogenic factor TSP-1. CONCLUSION: Hyperaemia-induced angiogenesis, likely in response to elevated shear stress, is independent of the vasodilator involved, with a rapid induction and quick regression following the stimulus withdrawal. PMID- 27261203 TI - Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo. AB - OBJECTIVE: Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. METHODS: Sun-protected buttock skin (76 +/- 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. RESULTS: Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-beta/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. CONCLUSION: 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human skin. PMID- 27261204 TI - A Predictive Model to Estimate Cost Savings of a Novel Diagnostic Blood Panel for Diagnosis of Diarrhea-predominant Irritable Bowel Syndrome. AB - PURPOSE: A high incidence of irritable bowel syndrome (IBS) is associated with significant medical costs. Diarrhea-predominant IBS (IBS-D) is diagnosed on the basis of clinical presentation and diagnostic test results and procedures that exclude other conditions. This study was conducted to estimate the potential cost savings of a novel IBS diagnostic blood panel that tests for the presence of antibodies to cytolethal distending toxin B and anti-vinculin associated with IBS D. METHODS: A cost-minimization (CM) decision tree model was used to compare the costs of a novel IBS diagnostic blood panel pathway versus an exclusionary diagnostic pathway (ie, standard of care). The probability that patients proceed to treatment was modeled as a function of sensitivity, specificity, and likelihood ratios of the individual biomarker tests. One-way sensitivity analyses were performed for key variables, and a break-even analysis was performed for the pretest probability of IBS-D. Budget impact analysis of the CM model was extrapolated to a health plan with 1 million covered lives. FINDINGS: The CM model (base-case) predicted $509 cost savings for the novel IBS diagnostic blood panel versus the exclusionary diagnostic pathway because of the avoidance of downstream testing (eg, colonoscopy, computed tomography scans). Sensitivity analysis indicated that an increase in both positive likelihood ratios modestly increased cost savings. Break-even analysis estimated that the pretest probability of disease would be 0.451 to attain cost neutrality. The budget impact analysis predicted a cost savings of $3,634,006 ($0.30 per member per month). IMPLICATIONS: The novel IBS diagnostic blood panel may yield significant cost savings by allowing patients to proceed to treatment earlier, thereby avoiding unnecessary testing. PMID- 27261202 TI - The democratization of gene editing: Insights from site-specific cleavage and double-strand break repair. AB - DNA double-strand breaks (DSBs) are dangerous lesions that if not properly repaired can lead to genomic change or cell death. Organisms have developed several pathways and have many factors devoted to repairing DSBs, which broadly occurs by homologous recombination, which relies on an identical or homologous sequence to template repair, or nonhomologous end-joining. Much of our understanding of these repair mechanisms has come from the study of induced DNA cleavage by site-specific endonucleases. In addition to their biological role, these cellular pathways can be co-opted for gene editing to study gene function or for gene therapy or other applications. While the first gene editing experiments were done more than 20 years ago, the recent discovery of RNA-guided endonucleases has simplified approaches developed over the years to make gene editing an approach that is available to the entire biomedical research community. Here, we review DSB repair mechanisms and site-specific cleavage systems that have provided insight into these mechanisms and led to the current gene editing revolution. PMID- 27261205 TI - Cardiovascular Disease Risk Associated With Familial Hypercholesterolemia: A Systematic Review of the Literature. AB - PURPOSE: The goal of this study was to determine cardiovascular disease (CVD) risk associated with familial hypercholesterolemia (FH). METHODS: A systematic review of the published literature was conducted. All publications describing FH risk from PubMed ("cardiovascular disease risk + familial hypercholesterolaemia," 2004-2015), Internet and Medline search of FH registries, and associated references were screened for FH-related CVD risk in titles, abstracts, and study methods. CVD risk expressed as rates, odds, or ratios of mortality and morbidity were extracted. Each article was reviewed for bias by 2 reviewers within 17 items in 7 categories; a modified Newcastle-Ottawa assessment scale was used for nonrandomized studies. FINDINGS: The complete literature search identified 712 potential publications: 549 from PubMed (Medline), 150 from registries, and 13 from references. Fourteen articles met the inclusion criteria: 8 from registries in the United Kingdom, the Netherlands, Norway, and Spain; 5 from single hospitals or families in Japan, Denmark, the Netherlands, and the United Kingdom; and a population survey in Denmark. Across studies, attrition bias was low in 22 (80%) of 28 items. Risk of selection bias was high in 35 (63%) of 56 items. Selection bias risk was due to low representativeness and lack of a non-FH comparator group within the same study; detection bias risk was due to variable definitions of CVD outcomes/measurement; and performance bias risk was due to long-term, intensive treatment, the most common limitations for registries. Studies from single hospitals and families lacked generalizability. In contrast, the Danish study revealed a low bias in each of the 4 selection bias criteria and 2 attrition risk criteria. Fatal and nonfatal CVD events were collected in the study. Comparing patients with FH versus non-FH patients, the odds ratios for coronary artery disease were 10.3 (95% CI, 7.8-13.8) and 13.2 (95% CI, 10.0-17.4) in subjects treated and not treated with lipid-lowering therapy, respectively. These ratios fall within the ranges of ratios reported in other studies but are generally higher than the ratios from registries and clinics, in which intensive specialized management is available. IMPLICATIONS: There is a lack of available data describing CVD risk in patients with FH, and many of the existing studies have biases in their design that could affect their risk estimates. A Danish study had the highest quality based on a predefined quality check list, providing the most credible estimates of the increase in CVD risk in patients with FH. The CVD risk due to FH is high and represents unmet medical need for patients with FH. Further research is warranted to validate the magnitude of risk. PMID- 27261206 TI - Pure and Mixed Mucinous Carcinoma of the Breast: A Comparison of Clinical Outcomes and Treatment Results. AB - Mucinous breast carcinoma (MBC) carcinoma represents approximately 1-6% of all malignant breast carcinoma and is divided into pure (PMBC) and mixed (MMBC) subtypes. This study presents the comparison of clinical characteristics and treatment results in 70 patients with PMBC and 40 patients with MMBC, treated at a single institution during 25 years. Performed analyses showed that only nodal status was different in both subtypes. Patients with MMBC showed a significantly higher incidence of axillary nodal metastases in comparison to PMBC (25% versus 10%, respectively). Instead, the 10-year disease-free survival rate was significant higher in PMBC than MMBC (85.7% versus 65%, p < 0.02, test log rank). Authors own observations and data from literature proved that MMBC should be considered as subtypes of mucinous breast cancer. PMID- 27261207 TI - Triple-site pacing for cardiac resynchronization in atrial fibrillation - an opening onto different scenarios. PMID- 27261208 TI - Severe left ventricular outflow tract obstruction. PMID- 27261209 TI - Risk stratification in acute coronary syndromes - when perfect is the enemy of good. PMID- 27261210 TI - BRAF V600E mutation in metastatic colorectal cancer: Methods of detection and correlation with clinical and pathologic features. AB - The screening for BRAF V600E mutation is employed in clinical practice for its prognostic and potentially predictive role in patients with metastatic colorectal carcinoma (mCRC). Little information is available on the sensitivity and specificity of the testing methods to detect this mutation in CRC. By using serial dilution of BRAF mutant DNA with wild type DNA, we found that the sensitivity of allelic discrimination-Real Time PCR was higher than PCR Sequencing (10% vs 20%). In agreement, the Real Time PCR assay displayed increased analytical sensitivity in detecting the BRAF V600E mutation as compared with PCR-Sequencing in a cohort of 510 consecutive CRCs (21 vs 16 cases). Targeted resequencing demonstrated that all cases negative by PCR-Sequencing had an allelic frequency of the BRAF mutation <20%, thus suggesting tumor heterogeneity. The association of BRAF mutations with clinical and pathological features was assessed next in a cohort of 840 KRAS exon 2 wild type CRC patients screened with the Real Time PCR assay. The BRAF V600E mutation frequency in this cohort was 7.8% that increased to 33.4% in females over 70 y of age with right sided tumor location. BRAF mutations were also detected in 4.4% of male patients with left-sided tumors and aged <70 y. Fourteen of 61 (22.9%) BRAF V600E mutation bearing patients exhibited microsatellite instability (MSI) as assessed by T17 mononucleotide sequence within intron 8 of HSP110. Our study indicates that Real Time PCR-based assays are more sensitive than PCR-Sequencing to detect the BRAF V600E mutation in CRC and that BRAF mutations screening should not be restricted to selected patients on the basis of the clinical-pathological characteristics. PMID- 27261211 TI - Editorial on "What is a potentially damaging vaccination delay in children younger than 2 years?" AB - Control of hepatitis B through routine infant immunization in more than 95% of countries has reduced the prevalence of chronic hepatitis carriers to less than 1%-2% in immunized cohorts of children even in high endemicity countries. In that context the authors of this editorial found the results of a paper by Gras et al in this issue concerning. They performed a Delphi survey of 37 French immunization experts and the results concluded that delayed hepatitis B immunization would cause "potential damage" only after 11 years. Large cohorts of French children and adolescents remain susceptible to hepatitis B infection. Given the high rates of immigration to France from areas of higher endemicity, the higher birth rate and degree of integration of these groups into the health system, plus the lower age of sexual debut and the use of injectable drugs in the general population, we cannot agree that a delay of 11 years is acceptable. Rates of adolescent immunization are quite low so relying on protection at this age will yield little in terms of population protection. Loss of confidence in Hepatitis B vaccine following disproved allegations that the vaccine caused Multiple Sclerosis persists in France, and we believe the results of this paper sends a damaging message to health workers and parents in France and beyond. PMID- 27261212 TI - Testing the fading affect bias for healthy coping in the context of death. AB - Affect fades faster for unpleasant events than for pleasant events (e.g., Walker, Vogl, & Thompson, 1997 ), which is referred to as the fading affect bias (FAB; Walker, Skowronski, Gibbons, Vogl, & Thompson, 2003 ). Although research has generally shown that the FAB is a healthy coping mechanism, this same finding has not been demonstrated at a specific level of analysis accounting for particular event types and related individual differences (e.g., Gibbons et al., 2013 ). Given the strong unpleasant emotions associated with death (Rask, Kaunonen, & Paunonen-Ilmonen, 2002 ), the current study examined FAB in the context of death events and participant attitudes toward death. General healthy coping was shown by robust FAB across death and control (i.e., everyday) events and by a negative correlation between negative religious coping and FAB. Although healthy coping at a specific level of analysis was supported by increased FAB for participants who held accepting attitudes toward death when they recalled everyday events, it was not supported by decreased FAB for the same participants when they recalled death events. This effect was mediated by rehearsal ratings, not depression. Implications are discussed. PMID- 27261213 TI - New insights on amygdala: Basomedial amygdala regulates the physiological response to social novelty. AB - The amygdala has been associated with a variety of functions linked to physiological, behavioral and endocrine responses during emotional situations. This brain region is comprised of multiple sub-nuclei. These sub-nuclei belong to the same structure, but may be involved in different functions, thereby making the study of each sub-nuclei important. Yet, the involvement of the basomedial amygdala (BMA) in the regulation of emotional states has yet to be defined. Therefore, the aim of our study was to investigate the regulatory role of the BMA on the responses evoked during a social novelty model and whether the regulatory role depended on an interaction with the dorsomedial hypothalamus (DMH). Our results showed that the chemical inhibition of the BMA by the microinjection of muscimol (gamma-aminobutyric acid (GABAA) agonist) promoted increases in mean arterial pressure (MAP) and heart rate (HR), whereas the chemical inhibition of regions near the BMA did not induce such cardiovascular changes. In contrast, the BMA chemical activation by the bilateral microinjection of bicuculline methiodide (BMI; GABAA antagonist), blocked the increases in MAP and HR observed when an intruder rat was suddenly introduced into the cage of a resident rat, and confined to the small cage for 15min. Additionally, the increase in HR and MAP induced by BMA inhibition were eliminated by DMH chemical inhibition. Thus, our data reveal that the BMA is under continuous GABAergic influence, and that its hyperactivation can reduce the physiological response induced by a social novelty condition, possibly by inhibiting DMH neurons. PMID- 27261214 TI - When an Intrauterine Device Is Not Intrauterine. PMID- 27261215 TI - Opportunistic Salpingectomy: We Chose to Act, Not Wait. PMID- 27261216 TI - La salpingectomie opportuniste : Nous choisissons d'agir, pas d'attendre. PMID- 27261217 TI - Determination of Gestational Age by Ultrasound: In Response. PMID- 27261218 TI - Management of Preterm Premature Rupture of Membranes: A Comparison of Inpatient and Outpatient Care. AB - OBJECTIVES: We sought to evaluate the safety of outpatient management of pregnancy complicated by preterm premature rupture of membranes (PPROM). STUDY DESIGN: We performed a retrospective cohort study of women with PPROM and a latency period of at least one week in one provincial health region between January 2007 and December 2012. We evaluated pregnancy outcomes for 133 women whose cases were managed using specialized community care and compared these with outcomes of a similar group of 122 women whose cases were managed entirely in the hospital. The primary outcome measured was the difference in the latency period between the two groups. For categorical variable outcomes, data were analyzed using chi-square tests, and continuous variable outcomes were compared using t tests. RESULTS: The median latency period for inpatients was 11 days compared with 18 days for patients in the community (P < 0.001). The most common reason for delivery was spontaneous labour (57% of inpatients and 50% of outpatients). Rates of stillbirth and neonatal mortality were similar between the two groups (3% in the inpatient group and 4% in the outpatient group). Precipitous vaginal delivery of a preterm breech infant was associated with mortality. Umbilical cord pH was < 7.10 in 5% of the inpatient group and 3% of the outpatient group. Median Apgar scores were slightly higher among the outpatient group. CONCLUSION: The safety of outpatient management of appropriately selected patients with PPROM is comparable with the safety of in-hospital management. Patients with PPROM and a fetus in breech presentation may not be appropriate for outpatient management, especially prior to 28 weeks' gestation. The decision to manage a patient with PPROM on an outpatient basis must be made after careful evaluation, with a thorough discussion of the risks and benefits and with serial reassessment of patient suitability. PMID- 27261219 TI - Chorionic Villus Sampling, Early Amniocentesis, and Termination of Pregnancy Without Diagnostic Testing: Comparison of Fetal Risk Following Positive Non invasive Prenatal Testing. AB - BACKGROUND: With the increased accuracy of non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) techniques, the likelihood of false-positive screening results has been reduced for high-risk populations. Following a positive screening test, a diagnostic procedure to confirm the result is strongly recommended, although some patients have terminated pregnancies because of a positive NIPT alone. Chorionic villus sampling (CVS), the diagnostic procedure of choice in the first trimester, is not available in all locations. Amniocentesis before 15 weeks, referred to as early amniocentesis (EA), is associated with a 1% rate of talipes and an increased rate of early pregnancy loss compared with CVS. Our objective was to compare the level of risk for euploid pregnancies following a positive NIPT based on the invasive procedure chosen. METHOD: Using data from a 2003 meta-analysis, we estimated the rates of adverse pregnancy outcome in euploid pregnancies based on the positive predictive value (PPV) of NIPT and the invasive procedure used-that is, CVS, EA, or termination of pregnancy (TOP). RESULTS: Following NIPT, we found that the rate of adverse fetal outcomes in euploid pregnancies was lower for CVS than for EA at all PPV levels. As the PPV of NIPT increased, the difference in risk between EA and CVS decreased. The risk to euploid pregnancies of TOP was excessive at all PPVs. CONCLUSION: CVS is the recommended diagnostic test in the first trimester because it is safer than EA for the fetus. However, EA is better than no testing when early TOP is planned. Patients should be strongly counselled against TOP without confirmatory testing. PMID- 27261220 TI - A Streamlined Surgical Approach to Laparoscopic Sacrocolpopexy for Post Hysterectomy Vault Prolapse. AB - OBJECTIVE: To describe a streamlined laparoscopic sacrocolpopexy (LSCP) surgical technique in women with post-hysterectomy vault prolapse and to evaluate the functional outcomes, complication rates, and surgical morbidity within our centre. METHODS: We retrospectively reviewed the charts of 180 patients scheduled for LSCP between November 2002 and May 2013 in a tertiary care centre. Patients were followed-up at six weeks, six months, and yearly after surgery. We reviewed patient demographics, preoperative and postoperative symptoms, and perioperative variables. Objective success of the surgery was defined as having a less than stage 2 vault prolapse, and subjective success was defined as the absence of bulge or prolapse symptoms. Success and complication rates were calculated. RESULTS: Of the 180 patients who underwent surgery, 144 patients underwent the procedure as planned and had at least six months of follow-up. At the last follow up visit, 133 of these 144 patients (92.4%) were free of prolapse symptoms. Several bladder and bowel symptoms showed significant improvement. Anatomical success of vault support was achieved in 140 of 144 patients (97.2%), and 119 patients (82.6%) had no prolapse beyond the hymen. Early complications (within the first 6 weeks) occurred in 8.3% of 162 patients with limited outcome data, and late complications (after 6 weeks) occurred in 11.5% of the 144 patients with long-term data. There were no cystotomies or mesh exposures. CONCLUSION: At an average of 32 months, this cohort of patients had low prolapse recurrence rates and no reports of cystotomy or mesh erosion. The abridged LSCP technique, as practised in our institution, is safe and effective in the surgical management of post-hysterectomy vault prolapse. PMID- 27261221 TI - Intrauterine Adhesions Following Miscarriage: Look and Learn. AB - OBJECTIVE: To examine the incidence of intrauterine adhesions (IUA) following the management of miscarriage in women with previously documented normal uterine cavities. METHODS: We conducted a retrospective cohort study from two fertility clinics with standard practice protocols for evaluating the uterine cavity prior to infertility treatment and following clinical pregnancy loss. A database query and manual chart review identified 144 women with normal uterine cavities who experienced a miscarriage between January 2010 and November 2012 and returned to the clinic for follow-up hysteroscopy. Following documentation of a non-viable clinical pregnancy using transvaginal ultrasound, patients chose expectant, medical, or surgical management according to standardized clinical protocols. The primary outcome was the detection of IUA. Secondary outcomes included the presence of retained products of conception and various risk factors associated with the development of IUA. RESULTS: The incidence of IUA following early pregnancy loss was 6.3%. There were no significant differences in patient characteristics between those with and without IUA. There was a significant association between IUA and increasing uterine size, particularly in the presence of multiple gestation (P = 0.039). Mechanical suction dilatation and curettage (D&C) was a risk factor for IUA, but manual vacuum aspiration was not a risk factor (P = 0.003). Retained products of conception were found in 13.9% of study participants, and the incidence did not differ among management options. CONCLUSIONS: This appears to be the first documentation of IUA that were entirely attributable to the index miscarriage or its management. There appears to be an increased risk of IUA following D&C with larger uteri and multiple pregnancies and following mechanical suction D&C. PMID- 27261223 TI - Early Short Stimulation Modified Natural Cycle IVF With GnRH Agonist Trigger and In Vitro Maturation in a Woman with Polycystic Ovary Syndrome: A Case Report. AB - BACKGROUND: Gonadotropin-releasing hormone agonist (GnRHa) triggering of final oocyte maturation has been used successfully in GnRH antagonist IVF cycles. It has not been used to date in cycles in which immature oocytes are matured in vitro. CASE: We report here for the first time that GnRHa triggering in a variation on the modified natural IVF cycle can be used as a strategy in the treatment of infertility secondary to polycystic ovary syndrome. In this approach, follicles were stimulated with gonadotropins for three to five days when they were small, and triggering of ovulation occurred when the largest follicles were 10 to 12 mm in diameter. This was followed by retrieval of many immature oocytes that were matured in vitro and subsequently developed to form blastocysts that resulted in a live birth. CONCLUSION: This is the first human evidence that GnRHa triggering of ovulation can be used successfully when the aim is in vitro maturation of oocytes. PMID- 27261222 TI - Randomized Trial Comparing the Effect of Endometrial Shedding With Medroxyprogesterone Acetate With Random Start of Clomiphene Citrate for Ovulation Induction in Oligo-ovulatory and Anovulatory Women. AB - OBJECTIVE: A recent retrospective study demonstrated that anovulatory infertile women who did not have a progestogen-induced withdrawal bleed before treatment with clomiphene citrate (CC) had higher pregnancy rates than women who had a withdrawal bleed and those who had spontaneous menstrual bleeding. We sought to assess endometrial thickness at the time of ovulation in oligo-ovulatory and anovulatory women who took CC with or without a preceding progestogen-induced withdrawal bleed. METHODS: We conducted a pilot randomized trial in which women with infertility and oligomenorrhea or amenorrhea were randomly assigned to take either CC after a withdrawal bleed induced by medroxyprogesterone acetate (MPA) 10 mg daily for 10 days or to take CC without such a bleed. Study participants underwent cycle monitoring with ultrasound assessment of endometrial thickness at the time of LH surge or a human chorionic gonadotropin trigger, followed by timed intercourse or intrauterine insemination. Women who had not ovulated by cycle day 21 took an increased dose of CC, with or without an MPA-induced withdrawal bleed, to a maximum of three cycles. Participants and nurses were asked to complete a questionnaire about the study. RESULTS: There was no significant difference in endometrial thickness on the day of LH surge or human chorionic gonadotropin trigger between women who had a progestogen-induced withdrawal bleed and those who did not (P = 0.65). On average, the time to ovulation was 15 days longer in women who took MPA than in women who did not, but this difference was not statistically significant (P = 0.65). Satisfaction with the study was reported as high by both patients and nurses. CONCLUSION: In anovulatory or oligo-ovulatory women treated with CC, we found no significant difference in endometrial thickness whether or not the use of CC was preceded by a withdrawal bleed induced by MPA. PMID- 27261225 TI - Readiness for malignant hyperthermia can be survey stumbling block. PMID- 27261224 TI - A Review of Consent Documents From Canadian IVF Clinics, 1991 to 2014. AB - OBJECTIVE: We reviewed the content of IVF consent documents (i.e., consent forms and accompanying information sheets) used by Canadian IVF clinics in 1991, 2004, and 2014, paying particular attention to the inclusion of information that should be provided to patients in accordance with minimum ethical standards for disclosure. METHODS: We contacted all Canadian IVF clinics in operation in 1991 (17 clinics), 2004 (24 clinics), and 2014 (35 clinics) by mail and requested blank copies of their IVF consent documents. Documents received were reviewed for the inclusion of information about the nature of IVF, the potential benefits of IVF, the potential harms and inconveniences of IVF, confidentiality, voluntariness, and options for the use or discarding of embryos not transferred in the original stimulated cycle (sometimes referred to as supernumerary, excess, or spare embryos). RESULTS: We received responses from 11 of 17 clinics operating in 1991 (response rate 65%), 14 of 24 clinics operating in 2004 (response rate 58%), and 11 of 35 clinics operating in 2014 (response rate 31%). In general, comparisons of the 1991, 2004, and 2014 data sets showed a long-term decrease in documented disclosure of information that should be provided to patients in accordance with minimum ethical standards. The only cases in which this trend appeared to be reversed was with disclosure about the probability of supernumerary embryos, long-term risks of treatment, the right to revoke consent to the use or discarding of supernumerary embryos, and some of the options for the use of supernumerary embryos. In these few instances, there was a notable improvement in the disclosure of relevant information between 1991 and 2014. CONCLUSION: The disclosure of information relevant to the interests of those undergoing IVF and those who are born as a result of IVF appears to be decreasing. Furthermore, the information that increasingly is being disclosed in consent documents appears to be directing the orientation and content of these documents away from the primary interests of the relevant women, couples, and children. These two trends are inconsistent with the goal of informed consent. PMID- 27261226 TI - Pimavanserin approved for Parkinson's-related hallucinations, delusions. PMID- 27261227 TI - Maine enacts statewide limits on opioid prescribing. PMID- 27261228 TI - New drugs and dosage forms. PMID- 27261229 TI - In Indiana, decongestant access hinges partly on pharmacists' judgment. PMID- 27261231 TI - Phytonadione oral liquid. PMID- 27261232 TI - Is i.v. acetaminophen really superior? PMID- 27261233 TI - Effect of breastfeeding on neonatal abstinence syndrome. PMID- 27261234 TI - Prospective inventory management systems for preempting problems related to medication unavailability. PMID- 27261235 TI - Facilitating alteplase delivery for patients with stroke. PMID- 27261236 TI - Pharmacy's influence and opportunity in public health. PMID- 27261237 TI - Pharmacologic management of angioedema induced by angiotensin-converting enzyme inhibitors. AB - PURPOSE: The published evidence on pharmacologic approaches to the management of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema is reviewed. SUMMARY: Angioedema is a serious, potentially life-threatening adverse effect of ACEI use. Although the underlying mechanism is not fully understood, excess bradykinin produced through a complex interplay between the kallikrein-kinin and renin-angiotensin-aldosterone systems is thought to play a major role. The nonallergic nature of the reaction renders traditional therapies (corticosteroids and antihistamines) ineffective because those agents do not modify the proposed pathophysiology. Fresh frozen plasma (FFP) provides kinase II, a protein that breaks down bradykinin. Case reports support FFP as a treatment for ACEI-induced angioedema, but no formal evaluations have been completed to date. Both ecallantide and complement 1 esterase (C1) inhibitor concentrate reduce bradykinin production through upstream inhibition of kallikrein. C1 inhibitor concentrate has been used successfully to manage ACEI-induced angioedema in a few reported cases, but robust supportive studies are lacking. Conversely, ecallantide has been evaluated in multiple randomized trials but has not been shown to offer advantages over traditional therapies. The use of icatibant, a direct antagonist of bradykinin B2 receptors, was reported to be beneficial in several case reports and in a small Phase II study, safely and rapidly reducing symptoms of ACEI-induced angioedema. An ongoing Phase III trial (NCT01919801) will better define the role of icatibant in the management of ACEI-induced angioedema. CONCLUSION: FFP, C1 inhibitor, and icatibant appear to be safe and effective therapeutic options for the management of ACEI-induced angioedema, whereas it appears ecallantide should be avoided. PMID- 27261238 TI - Intravenous lipid emulsion and high-dose insulin as adjunctive therapy for propranolol toxicity in a pediatric patient. AB - PURPOSE: The concurrent use of intravenous lipid emulsion (ILE) and high-dose insulin (HDI) for the management and treatment of propranolol toxicity in a pediatric patient is described. SUMMARY: A seven-month-old infant (weight, 6.1 kg) was admitted to a hospital emergency department with lethargy and bradycardia after an unintentional overdose of propranolol suspension, which had been prescribed several days previously for treatment of a scalp hemangioma. Notable physical examination and laboratory findings were as follows: blood pressure, 121/84 mm Hg (normal range, 90 +/- 30/60 +/- 10 mm Hg); heart rate, 62 beats/min (normal range, 100-150 beats/min); respiratory rate, 24 breaths/min (normal range, 25-35 breaths/min); oxygen saturation, 100% on room air; and rectal temperature, 35.7 degrees C (normal range, 36.6-38.0 degrees C). The patient was lethargic. Treatment included i.v. fluid boluses of 0.9% sodium chloride injection and i.v. boluses and continuous infusions of HDI, dextrose, and ILE. After the completion of these treatments, hemodynamic stability was regained. The case is believed to be the first reported case in which a pediatric patient less than one year of age regained hemodynamic stability after administration of ILE and HDI rescue therapy. Monitoring blood glucose frequently with HDI is essential to avoid hypoglycemia. The rationale for using ILE and HDI for reversal of drug toxicities is discussed. CONCLUSION: A symptomatic pediatric patient with acute propranolol toxicity exhibited clinical improvement with the administration of ILE in conjunction with HDI. PMID- 27261239 TI - Risk factors for i.v. compounding errors when using an automated workflow management system. AB - PURPOSE: Results of a study to determine the frequency of and risk factors for errors in automated compounding of i.v. medication doses at a pediatric hospital are presented. METHODS: Data compiled by the hospital's automated i.v. compounding workflow management system over a 12-month period were analyzed. A descriptive analysis was conducted to characterize intercepted errors by frequency and type. Multivariate regression analysis via a backward stepwise procedure was performed to identify notable risk factors for i.v. compounding errors. RESULTS: Among the 421,730 i.v. doses evaluated, there were 3,101 documented errors (an overall error rate of 0.74%). The automated system intercepted 72.27% of the errors, mainly those containing an incorrect drug or diluent. The remaining 27.73% of i.v. compounding errors, primarily dose preparation in the wrong volume (21.51%) or damage to the final product (0.93%), were identified during final inspection by a pharmacist. The logistic regression model showed that four factors were significantly (p < 0.05) associated with an increased risk of compounding errors: dose preparation during the morning shift (relative risk [RR], 1.84; 95% CI, 1.68-2.02) or on a Sunday (RR, 1.28; 95% CI, 1.11-1.47), preparation of doses for use in critical care units (RR, 1.17; 95% CI, 1.07-1.28), and technician versus pharmacist compounding (RR, 1.17; 95% CI, 1.04-1.32). CONCLUSION: Analysis of error reports generated by an i.v. compounding workflow management system at a large pediatric hospital over one year found an overall rate of detected errors of 0.74%. Four factors were identified as significant predictors of increased error risk. PMID- 27261240 TI - Impact of resident research publication on early-career publication success. AB - PURPOSE: The impact of resident research publication on early-career publication success is evaluated. METHODS: This study included a retrospective cohort of pharmacy residents' abstracts presented at the Great Lakes Pharmacy Resident Conference (GLPRC). Published residency research projects at GLPRC (n = 76) were matched 1:1 to unpublished projects. Residents were followed forward for five years to identify early-career publications (postresidency publication positive) versus no publications (postresidency publication negative). The following characteristics of postresidency publication-positive and publication-negative residents were compared: publication of residency project, university-affiliated residencies, median number and interquartile range of coinvestigators, presence of a physician coinvestigator, highest nonphysician H-index of coinvestigators, and nonphysician H-index of >=1 for any coinvestigator (indicating that a coinvestigator has previously published and been cited). RESULTS: A total of 152 abstracts were reviewed (76 published and 76 unpublished projects). Using a predefined systematic search strategy, 55 former residents had a postresidency publication within five years after presenting their project at the GLPRC. Of the former residents who published their residency project, 38 (50%) were postresidency publication positive, while 17 former residents (22.4%) who did not publish resident research projects were postresidency publication positive. Univariate and multivariate analyses revealed that publication of the pharmacy resident research project and a university-affiliated residency program was positively associated with postresidency publication success. CONCLUSION: Pharmacy residents who published their residency research project after its presentation at the GLPRC were twice as likely to have publication success within five years compared with residents who did not publish their residency research project. A university-affiliated residency was associated with postresidency publication success within five years after project presentation. PMID- 27261241 TI - Opioid prescription fill rates after emergency department discharge. AB - PURPOSE: Opioid prescription fill rates and the time to fill after emergency department (ED) discharge were studied. METHODS: Data were evaluated for all patients discharged from the ED between September 1, 2011, who were February 1, 2012, who were diagnosed with one of the following: dental pain, jaw pain, flank pain, abdominal pain, pelvic pain, back pain, neck pain, knee pain, headache, fracture, or sprain. Clinical information was abstracted via computer algorithm, and prescription filling within 100 days of prescription writing was determined by cross-referencing patient demographics with the state prescription drug monitoring program. Logistic regression analysis and a Cox proportional hazards model were used to determine if any clinical and demographic characteristics were associated with fill rates or the time to fill, respectively. RESULTS: Of the 2243 patients who received an opioid prescription at ED discharge, 1775 (79%) filled it, with a median time to fill of 0 days. On adjusted analysis, characteristics associated with filling the opioid prescriptions included Caucasian race, being insured by the federal government or through a state indigent assistance program, a chief complaint of back pain, and a history of filling an opioid prescription within the past year. No characteristics were predictive of a prolonged time to filling. CONCLUSION: One in five patients who received an opioid prescription at discharge from an urban academic ED did not fill it. Several factors may be associated with a greater likelihood of filling, such as insurance status and history of filling an opioid prescription within the past year. PMID- 27261242 TI - ASHP Guidelines on Evaluating and Using Home or Alternate-Site Infusion Service Providers. PMID- 27261243 TI - ASHP Statement on the Roles of Pharmacy Technicians. PMID- 27261244 TI - Creating an animation-enhanced video library of hepato-pancreato-biliary and transplantation surgical procedures. AB - The potential for integrating real-time surgical video and state-of-the art animation techniques has not been widely applied to surgical education. This paper describes the use of new technology for creating videos of liver, pancreas and transplant surgery, annotating them with 3D animations, resulting in a freely accessible online resource: The Toronto Video Atlas of Liver, Pancreas and Transplant Surgery ( http://tvasurg.ca ). The atlas complements the teaching provided to trainees in the operating room, and the techniques described in this study can be readily adapted by other surgical training programmes. PMID- 27261245 TI - Intranasal volume increases with age: Computed tomography volumetric analysis in adults. AB - OBJECTIVES/HYPOTHESIS: It is theorized that intranasal cavity volumes change throughout the aging process, possibly secondary to hormonal changes and atrophy of the sinonasal mucosa. Our objective is to compare intranasal volumes from different age groups to test the hypothesis that intranasal cavity volume increases with age. STUDY DESIGN: Case series. METHODS: An analysis of computed tomography (CT) scans performed for reasons other than sinonasal complaints. Intranasal volumes of three groups (age 20-30 years, 40-50 years, and 70 years and above) were calculated using Vitrea software. The total intranasal volume was measured from the nasal vestibule anteriorly, the nasopharynx posteriorly, the olfactory cleft superiorly, and the nasal floor inferiorly. The total volume included the sum of the right and left sides. RESULTS: Sixty-two CT scans were analyzed. There was a progressive, relatively linear, increase in intranasal volume with increasing age: 20 to 30 years = 15.73 mL, 40 to 50 years = 17.30 mL, and 70 years and above = 18.38 mL. Mean intranasal volume for males was 19.07 mL, and for females was 15.23 mL. Analysis of variance demonstrated significant group differences in mean intranasal volume for age (P = .003) and gender (P < .001), with moderate-to-large effect size of 0.206 and 0.289 (partial eta(2) ), respectively. Post hoc testing revealed a significant difference between the 20 to 30-year and >70-year age groups (P = .006). There was no significant difference in intranasal volume dependent upon body mass index. CONCLUSIONS: Intranasal volume increases with age and is larger in males. Specific etiologies responsible for increased intranasal cavity volume with age are actively being evaluated. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2212-2215, 2016. PMID- 27261246 TI - Family needs of critically ill patients in the emergency department. AB - INTRODUCTION: Family members' experience a range of physiological, psychological and emotional impacts when accompanying a critically ill relative in the emergency department. Family needs are influenced by their culture and the context of care, and accurate clinician understanding of these needs is essential for patient- and family-centered care delivery. The aim of this study was to describe the needs of Taiwanese family members accompanying critically ill patients in the emergency department while waiting for an inpatient bed and compare these to the perceptions of emergency nurses. METHODS: A prospective cross-sectional survey was conducted in a large medical center in Taiwan. Data were collected from 150 family members and 150 emergency nurses who completed a Chinese version of the Critical Care Family Needs Inventory. RESULTS: Family members ranked needs related to 'communication with family members,' as most important, followed by 'family member participation in emergency department care', 'family member support' and 'organizational comfort'; rankings were similar to those of emergency nurses. Compared to nurses, family members reported higher scores for the importance of needs related to 'communication with family members' and 'family members' participation in emergency department care'. CONCLUSIONS: Family members place greater importance than emergency nurses on the need for effective communication. PMID- 27261247 TI - The prognostic impact of uric acid in patients with severely decompensated acute heart failure. AB - BACKGROUND: The serum level of uric acid (UA) is a well-known prognostic factor for heart failure (HF) patients. However, the prognostic impact of hyperuricemia and the factors that induce hyperuricemia in acute HF (AHF) patients are not well understood. METHODS AND RESULTS: Eight hundred eighty-nine AHF patients were enrolled in this study. The patients were assigned into a low UA group (UA<=7.0mg/dl, n=495) or a high UA group (UA>7.0mg/dl, n=394) according to their UA level on admission. A Kaplan-Meier curve showed that the survival rate of the low UA group was significantly higher than that of the high UA group. A multivariate Cox regression model identified that a high UA level (HR: 1.192, 95%CI 1.112-1.277) was an independent predictor of 180-day mortality. A multivariate logistic regression model for a high serum UA level on admission indicated that chronic kidney disease (CKD) (OR: 2.030, 95%CI: 1.298-3.176, p=0.002) and the administration of loop diuretics before admission (OR: 1.556, 95%CI: 1.010-2.397, p=0.045) were independent factors. The prognosis, including all-cause death and HF events, was significantly poorer among patients who had a high UA level who had previously used loop diuretics and among CKD patients with a high UA level than among other patients. CONCLUSIONS: The serum UA level was an independent predictor in patients who were hospitalized during an emergent situation for AHF. An elevated serum UA level on admission was associated with the presence of CKD and the use of loop diuretics. These factors were also associated with adverse outcomes in hyperuricemic patients with AHF. PMID- 27261248 TI - Good responders to catheter ablation for long-standing persistent atrial fibrillation: Clinical and genetic characteristics. AB - BACKGROUND: Radiofrequency catheter ablation (RFCA) for long-standing persistent atrial fibrillation (L-PeAF) is challenging and has a relatively high recurrence rate. We explored clinical and genetic characteristics associated with being good responders (no early or clinical recurrence within 12 months in the absence of anti-arrhythmic drugs) to RFCA among patients with L-PeAF. METHODS: Of 1319 patients in the Yonsei AF Ablation Cohort, this study included 141 consecutive patients with L-PeAF (80.9% male, age 57.8+/-9.7 years) who were followed >12 months after RFCA. RESULTS: During 25 (19-35) months follow-up, the recurrence rate was 39%, and 38 patients (27%) were categorized as good responders, those had a shorter AF duration (p=0.010), and smaller left atrial (LA) size (p=0.033) than others. The rs2106216 (16q22/ZFHX3) genetic polymorphism was independently associated with being a good responder in multivariate analysis (adjusted OR=2.70, 95% CI 1.41-5.14, p=0.003), after adjusting for LA size and AF duration. The rs2106261 had predictive value for clinical recurrence of AF after RFCA among patients with an AF duration 12-65 months (log rank, p=0.025). CONCLUSIONS: Despite a relatively high recurrence rate after RFCA for L-PeAF, patients with a shorter AF duration and smaller LA size showed a more favorable outcome. The rs2106216 polymorphism (ZFHX3) was independently associated with being good responders to RFCA for L-PeAF, especially with AF duration 12-65 months. PMID- 27261249 TI - A Novel Tool for the Assessment Oxidative Stress in Age-Related Macular Degeneration: Thiol/Disulfide Homeostasis Revisited. AB - PURPOSE: To investigate thiol/disulfide status using a novel automated assay in patients with age-related macular degeneration (AMD) compared to age-matched healthy controls. METHODS: A total of 64 AMD patients [51 (79%) non-exudative, 13 (21%) exudative AMD] and 21 age-matched healthy control subjects were enrolled in this study. Plasma total thiol, native thiol, disulfide levels were measured and native thiol/disulfide ratio (TDR) was calculated using a novel spectrophotometric assay. RESULTS: Patients with AMD had significantly lower levels of total thiol (434.8 +/- 7.0 MUmol/L vs. 472.2 +/- 7.9 MUmol/L, p < 0.001), native thiol (393.6 +/- 6.5 MUmol/L vs. 437.5 +/- 7.1 MUmol/L, p = 0.004) compared to healthy controls. However, plasma disulfide levels were higher in AMD patients (20.6 +/- 0.9 MUmol/L vs. 17.3 +/- 1.3 MUmol/L, p = 0.113) compared to healthy controls. The TDR was not statistically different between the early AMD group and healthy controls (24.2 +/- 2.3 vs. 29.5 +/- 3.1, p = 0.345). However, intermediate and advanced stage AMD groups had significantly lower levels of TDR compared to healthy controls (21.6 +/- 2.6 vs. 29.5 +/- 3.1, p = 0.023 and 20.3 +/- 1.2 vs. 29.5 +/- 3.1, p = 0.005, respectively). Native TDR was significantly lower in patients with exudative and non-exudative AMD (19.9 +/- 2.3 vs. 29.5 +/- 3.1, p = 0.024 and 21.8 +/- 1.14 vs. 29.47 +/- 3.1 respectively, p = 0.011). CONCLUSION: A greater extent of thiol consumption occurred in AMD patients compared to age-matched healthy controls. However, despite the similar levels of total thiol levels between several grades of AMD, the plasma native TDR value was decreased in accordance with the severity of the disease, which reflected the disease grade better. PMID- 27261250 TI - Ancient mitochondrial genomes clarify the evolutionary history of New Zealand's enigmatic acanthisittid wrens. AB - The New Zealand acanthisittid wrens are the sister-taxon to all other "perching birds" (Passeriformes) and - including recently extinct species - represent the most diverse endemic passerine family in New Zealand. Consequently, they are important for understanding both the early evolution of Passeriformes and the New Zealand biota. However, five of the seven species have become extinct since the arrival of humans in New Zealand, complicating evolutionary analyses. The results of morphological analyses have been largely equivocal, and no comprehensive genetic analysis of Acanthisittidae has been undertaken. We present novel mitochondrial genome sequences from four acanthisittid species (three extinct, one extant), allowing us to resolve the phylogeny and revise the taxonomy of acanthisittids. Reanalysis of morphological data in light of our genetic results confirms a close relationship between the extant rifleman (Acanthisitta chloris) and an extinct Miocene wren (Kuiornis indicator), making Kuiornis a useful calibration point for molecular dating of passerines. Our molecular dating analyses reveal that the stout-legged wrens (Pachyplichas) diverged relatively recently from a more gracile (Xenicus-like) ancestor. Further, our results suggest a possible Early Oligocene origin of the basal Lyall's wren (Traversia) lineage, which would imply that Acanthisittidae survived the Oligocene marine inundation of New Zealand and therefore that the inundation was not complete. PMID- 27261251 TI - Rapid divergence and gene flow at high latitudes shape the history of Holarctic ground squirrels (Urocitellus). AB - Across the animal tree of life, the prevalence and evolutionary role(s) of hybridization remain incompletely understood. Rapidly radiating clades can serve as important systems for investigating these issues; however, such groups are often characterized by additional, widespread sources of gene tree discordance (e.g., incomplete lineage sorting). In this paper, we employed a multilocus dataset, Bayesian gene tree inference, and multiple species tree reconstruction methods to infer phylogeny of Holarctic ground squirrels (Urocitellus). We tested phylogenetic hypotheses based on previous morphological, cytological and single locus datasets, and began to parse the causes of pervasive gene tree discordance that was observed. There is widespread incomplete lineage sorting in Urocitellus, consistent with rapid diversification embedded within the larger radiation of marmotine ground squirrels. We also recovered strong support for 2 instances of mitonuclear discord due to ancient hybridization among members of the high latitude parryii-richardsonii-elegans clade. These results add to a growing number of documented hybridization events in ground squirrels, suggesting their radiation is a fertile system for understanding the interplay of diversification and hybridization in animal evolution. PMID- 27261252 TI - Phylogeography of endemic Xantus' hummingbird (Hylocharis xantusii) shows a different history of vicariance in the Baja California Peninsula. AB - Studies of phylogeographic patterns provide insight into the processes driving lineage divergence in a particular region. To identify the processes that caused phylogeographic breaks, it is necessary to use historical information and a set of appropriate molecular data to explain current patterns. To understand the influence of geological or ecological processes on the phylogeography of the only species of hummingbird endemic to the Baja California Peninsula, Hylocharis xantusii, mitochondrial DNA sequences of three concatenated genes (Cyt-b, COI and ND2; 2297bp in total) in 100 individuals were analyzed. The spatial analyses of genetic variation showed phylogeographic structure consisting of a north, central and south regions. According to estimated divergence times, two vicariant events are supported, permanent separation of the peninsula and formation of the Gulf of California at 5mya and temporary isolation of the southern region at the Isthmus of La Paz at 3mya. The temporal frame of genetic differentiation of intraspecific haplotypes indicates that 90% of haplotypes diverged within the last 500,000years, with a population expansion 80,000years ago. Only four haplotypes diverged ~2.2 my and occurred in the south (Hxan_36, 38 and 45), and north (Hxan_45 and 56) regions; only haplotype 45 is shared between south and north populations. These regions also have the most recent haplotypes from 12,500 to 16,200years ago, and together with high levels of genetic diversity, we suggest two refuge areas, the Northern and Southern regions. Our results indicate that the phylogeographic pattern first results from vicariance processes, then is followed by historical and recent climate fluctuations that influenced conditions on the peninsula, and it is also related to oases distribution. This study presents the first investigation of phylogeography of the peninsular' endemic Xantus' hummingbird. PMID- 27261253 TI - Molecular phylogeny and species delimitation within the ciliate genus Spirostomum (Ciliophora, Postciliodesmatophora, Heterotrichea), using the internal transcribed spacer region. AB - Morphological and molecular delimitation of Spirostomum species is currently under debate. We addressed species boundaries within the genus Spirostomum, using the ITS1-5.8S-ITS2 region and the secondary structure of the ITS2 molecule, and 18S and 28S (D1D2) sequences additionally. The Spirostomum ITS region is among the shortest within the ciliates hitherto studied. The Spirostomum ITS2 molecule matches the "ring model", but exhibits only two helices radiating from a common loop. According to comparative analyses, they very likely correspond to helices II and III of other eukaryotes. Our phylogenetic analyses of the ITS region revealed a complex genealogical structure within the genus Spirostomum. However, boundaries among Spirostomum species could not be unambiguously determined either by phylogenetic trees, networks or sequence divergence cutoffs, because ITS2 sequences transcended species boundaries of the following morphospecies: S. ambiguum, S. minus, S. subtilis and S. teres. According to molecular diversity analysis, this is very likely caused by polymorphism in S. minus and S. teres, and by the lack of variability in S. ambiguum and S. subtilis. No compensatory base changes (CBCs) were detected in helices of the ITS2 molecule between different Spirostomum species, documenting that CBC analysis per se is not able to effectively discriminate Spirostomum species. PMID- 27261255 TI - Connections Underlying Translation and mRNA Stability. AB - Gene expression and regulation in organisms minimally depends on transcription by RNA polymerase and on the stability of the RNA product (for both coding and non coding RNAs). For coding RNAs, gene expression is further influenced by the amount of translation by the ribosome and by the stability of the protein product. The stabilities of these two classes of RNA, non-coding and coding, vary considerably: tRNAs and rRNAs tend to be long lived while mRNAs tend to be more short lived. Even among mRNAs, however, there is a considerable range in stability (ranging from seconds to hours in bacteria and up to days in metazoans), suggesting a significant role for stability in the regulation of gene expression. Here, we review recent experiments from bacteria, yeast and metazoans indicating that the stability of most mRNAs is broadly impacted by the actions of ribosomes that translate them. Ribosomal recognition of defective mRNAs triggers "mRNA surveillance" pathways that target the mRNA for degradation [Shoemaker and Green (2012) ]. More generally, even the stability of perfectly functional mRNAs appears to be dictated by overall rates of translation by the ribosome [Herrick et al. (1990), Presnyak et al. (2015) ]. Given that mRNAs are synthesized for the purpose of being translated into proteins, it is reassuring that such intimate connections between mRNA and the ribosome can drive biological regulation. In closing, we consider the likelihood that these connections between protein synthesis and mRNA stability are widespread or whether other modes of regulation dominate the mRNA stability landscape in higher organisms. PMID- 27261254 TI - Gangliosides of the Vertebrate Nervous System. AB - Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed of a sialylated glycan attached to a ceramide lipid, the same four structures-GM1, GD1a, GD1b, and GT1b-represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts-the dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, result in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect the aggregation of Abeta (Alzheimer's disease) and alpha-synuclein (Parkinson's Disease). As analytical, biochemical, and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases. PMID- 27261257 TI - Overview of Nucleotide Sugar Transporter Gene Family Functions Across Multiple Species. AB - Glycoproteins and glycolipids are crucial in a number of cellular processes, such as growth, development, and responses to external cues, among others. Polysaccharides, another class of sugar-containing molecules, also play important structural and signaling roles in the extracellular matrix. The additions of glycans to proteins and lipids, as well as polysaccharide synthesis, are processes that primarily occur in the Golgi apparatus, and the substrates used in this biosynthetic process are nucleotide sugars. These proteins, lipids, and polysaccharides are also modified by the addition of sulfate groups in the Golgi apparatus in a series of reactions where nucleotide sulfate is needed. The required nucleotide sugar substrates are mainly synthesized in the cytosol and transported into the Golgi apparatus by nucleotide sugar transporters (NSTs), which can additionally transport nucleotide sulfate. Due to the critical role of NSTs in eukaryotic organisms, any malfunction of these could change glycan and polysaccharide structures, thus affecting function and altering organism physiology. For example, mutations or deletion on NST genes lead to pathological conditions in humans or alter cell walls in plants. In recent years, many NSTs have been identified and functionally characterized, but several remain unanalyzed. This study examined existing information on functionally characterized NSTs and conducted a phylogenetic analysis of 257 NSTs predicted from nine animal and plant model species, as well as from protists and fungi. From this analysis, relationships between substrate specificity and the primary NST structure can be inferred, thereby advancing understandings of nucleotide sugar gene family functions across multiple species. PMID- 27261256 TI - Enterohaemorrhagic E. coli modulates an ARF6:Rab35 signaling axis to prevent recycling endosome maturation during infection. AB - Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC/EHEC) manipulate a plethora of host cell processes to establish infection of the gut mucosa. This manipulation is achieved via the injection of bacterial effector proteins into host cells using a Type III secretion system. We have previously reported that the conserved EHEC and EPEC effector EspG disrupts recycling endosome function, reducing cell surface levels of host receptors through accumulation of recycling cargo within the host cell. Here we report that EspG interacts specifically with the small GTPases ARF6 and Rab35 during infection. These interactions target EspG to endosomes and prevent Rab35-mediated recycling of cargo to the host cell surface. Furthermore, we show that EspG has no effect on Rab35-mediated uncoating of newly formed endosomes, and instead leads to the formation of enlarged EspG/TfR/Rab11 positive, EEA1/Clathrin negative stalled recycling structures. Thus, this paper provides a molecular framework to explain how EspG disrupts recycling whilst also reporting the first known simultaneous targeting of ARF6 and Rab35 by a bacterial pathogen. PMID- 27261258 TI - The Termination Phase in Protein Synthesis is not Obligatorily Followed by the RRF/EF-G-Dependent Recycling Phase. AB - It is general wisdom that termination of bacterial protein synthesis is obligatorily followed by recycling governed by the factors ribosomal recycling factor (RRF), EF-G, and IF3, where the ribosome dissociates into its subunits. In contrast, a recently described 70S-scanning mode of initiation holds that after termination, scanning of 70S can be triggered by fMet-tRNA to the initiation site of a downstream cistron. Here, we analyze the apparent conflict. We constructed a bicistronic mRNA coding for luciferases and showed with a highly resolved in vitro system that the expression of the second cistron did not at all depend on the presence of active RRF. An in vivo analysis cannot be performed in a straightforward way, since RRF is essential for viability and therefore, the RRF gene cannot be knocked out. However, we found an experimental window, where the RRF amount could be reduced to below 2.5%, and in this situation, the expression of the second cistron of a bicistronic luciferase mRNA was only moderately reduced. Both in vitro and in vivo results suggested that RRF-dependent recycling is not an obligatory step after termination, in agreement with the previous findings concerning 70S-scanning initiation. In this view, recycling after termination is a special case of the general RRF function, which happens whenever fMet-tRNA is not available for triggering 70S scanning. PMID- 27261259 TI - Crystal Structure of the Wild-Type Human GlyRS Bound with tRNA(Gly) in a Productive Conformation. AB - Aminoacyl-tRNA synthetases are essential components of the protein translational machinery in all living species, among which the human glycyl-tRNA synthetase (hGlyRS) is of great research interest because of its unique species-specific aminoacylation properties and noncanonical roles in the Charcot-Marie-Tooth neurological disease. However, the molecular mechanisms of how the enzyme carries out its classical and alternative functions are not well understood. Here, we report a complex structure of the wild-type hGlyRS bound with tRNA(Gly) at 2.95A. In the complex, the flexible Whep-TRS domain is visible in one of the subunits of the enzyme dimer, and the tRNA molecule is also completely resolved. At the active site, a glycyl-AMP molecule is synthesized and is waiting for the transfer of the glycyl moiety to occur. This cocrystal structure provides us with new details about the recognition mechanism in the intermediate stage during glycylation, which was not well elucidated in the previous crystal structures where the inhibitor AMPPNP was used for crystallization. More importantly, the structural and biochemical work conducted in the current and previous studies allows us to build a model of the full-length hGlyRS in complex with tRNA(Gly), which greatly helps us to understand the roles that insertions and the Whep-TRS domain play in the tRNA-binding process. Finally, through structure comparison with other class II aminoacyl-tRNA synthetases bound with their tRNA substrates, we found some commonalities of the aminoacylation mechanism between these enzymes. PMID- 27261260 TI - Molecular characterization and developmental expression patterns of apolipoprotein A-I in Senegalese sole (Solea senegalensis Kaup). AB - The apolipoprotein A-I (ApoA-I) is an essential component of the high density lipoproteins (HDL). In this study, the cDNA and genomic sequences of this apolipoprotein were characterized for first time in Solea senegalensis. The predicted polypeptide revealed conserved structural features including ten repeats in the lipid-binding domain and some residues involved in cholesterol interaction and binding. The gene structure analysis identified four exons and three introns. Moreover, the synteny analysis revealed that apoA-I did not localize with other apolipoproteins indicating a divergent evolution with respect to the apoA-IV and apoE cluster. The phylogenetic analyses identified two distinct apoA-I paralogs in Ostariophysi (referred to as Ia and Ib) and only one (Ib) in Acanthopterygii. Whole-mount in situ hybridization located the apoA-I signal mainly in the yolk syncytial layer in lecitotrophic larval stages. Later at mouth opening, the mRNA signals were detected mainly in liver and intestine compatible with its role in the HDL formation. Moreover, a clear signal was detected in some regions of the brain, retina and neural cord suggesting a role in local regulation of cholesterol homeostasis. After metamorphosis, apoA-I was also detected in other tissues such as gills, head kidney and spleen suggesting a putative role in immunity. Expression analyses in larvae fed two diets with different triacylglycerol levels indicated that apoA-I mRNA levels were more associated to larval size and development than dietary lipid levels. Finally, qPCR analyses of immature and mature transcripts revealed distinct expression profiles suggesting a posttranscriptional regulatory mechanism. PMID- 27261261 TI - Complete sequence of an IncFII plasmid harbouring the colistin resistance gene mcr-1 isolated from Belgian pig farms. PMID- 27261262 TI - Emergence of the colistin resistance mcr-1 determinant in commensal Escherichia coli from residents of long-term-care facilities in Italy. PMID- 27261263 TI - Detection of the plasmid-mediated colistin-resistance gene mcr-1 in clinical isolates and stool specimens obtained from hospitalized patients using a newly developed real-time PCR assay. PMID- 27261264 TI - A novel resistance mutation in eccC5 of the ESX-5 secretion system confers ofloxacin resistance in Mycobacterium tuberculosis. AB - BACKGROUND: Fluoroquinolone resistance in Mycobacterium tuberculosis is often conferred by DNA gyrase mutations. However, a substantial proportion of fluoroquinolone-resistant M. tuberculosis isolates do not have such mutations. METHODS: Ofloxacin-resistant and lineage-matched ofloxacin-susceptible M. tuberculosis isolates underwent WGS. Novel candidate resistance mutations were confirmed by Sanger sequencing and conferral of resistance was assessed via site directed mutagenesis and allelic exchange. Ofloxacin MIC was determined by resazurin microtitre assay (REMA) and the effects on MICs of efflux pump inhibitors (CCCP, reserpine and verapamil) were determined. RESULTS: Of 26 ofloxacin-resistant isolates, 8 (31%) did not have resistance-conferring DNA gyrase mutations. The V762G mutation in Rv1783 (eccC5, encoding a protein in the ESX-5 membrane complex secretion system) was present on WGS in 8/26 (31%) resistant isolates and 0/11 susceptible isolates (P = 0.005). The mutation was identified in five isolates without DNA gyrase mutations and three isolates with such mutations; it was identified in both European-American and East Asian M. tuberculosis lineages. The ofloxacin MIC increased from 1 to 32 mg/L after introduction of the V762G mutation into M. tuberculosis H37Rv. In this strain with the V762G mutation, ofloxacin MIC did not change in the presence of efflux pump inhibitors. CONCLUSIONS: A novel V762G mutation in Rv1783 conferred ofloxacin resistance in M. tuberculosis by a mechanism other than drug efflux. This occurred in a substantial proportion of resistant isolates, particularly those without DNA gyrase mutations. PMID- 27261265 TI - Ten years later: still a high prevalence of MRSA in slaughter pigs despite a significant reduction in antimicrobial usage in pigs the Netherlands. AB - OBJECTIVES: In 2005, 39% of pigs and 81% of the slaughter batches at Dutch slaughterhouses were MRSA positive. The objective of the present study was to investigate whether the 50% reduction of antimicrobial usage in finishing pigs in 2014 compared with 2009 in the Netherlands has led to a lower MRSA prevalence among Dutch slaughter pigs. METHODS: Nasal swabs from eight slaughter batches of on average 10 animals at seven slaughterhouses were taken and cultured using method 1, which was used in 2005, and method 2, using high-salt pre-enrichment. Suspected isolates were confirmed by PCR for two Staphylococcus aureus-specific DNA fragments and the mecA gene. A subset of MRSA isolates were further investigated using spa typing, multiple-locus variable number of tandem repeat analysis (MLVA) and antimicrobial susceptibility testing. RESULTS: Using methods 1 and 2, we found 461 of 558 (83%) and 552 of 558 (99%) of the pigs to carry MRSA in their nares, respectively. All 56 slaughter batches were MRSA positive. All MRSA isolates belonged to the livestock-associated MLVA complex 398, had a non-WT phenotype for tetracycline and spa type t011 predominated. CONCLUSIONS: A very high prevalence of nasal MRSA carriage was found in Dutch slaughter pigs and therefore the reduction in antimicrobial usage at the national level has not yet had an effect on the MRSA carriage rate of pigs entering the slaughterhouse. Therefore, there is still an increased risk of MRSA carriage for personnel working at pig slaughterhouses, particularly those having contact with living animals. Method 2, using high salt pre-enrichment, detected more MRSA-positive pigs and is currently the preferred method for screening of MRSA in livestock in the Netherlands. PMID- 27261266 TI - Comment on: Resistance gene naming and numbering: is it a new gene or not? PMID- 27261267 TI - Glutathione-S-transferase FosA6 of Klebsiella pneumoniae origin conferring fosfomycin resistance in ESBL-producing Escherichia coli. AB - OBJECTIVES: The objectives of this study were to elucidate the genetic context of a novel plasmid-mediated fosA variant, fosA6, conferring fosfomycin resistance and to characterize the kinetic properties of FosA6. METHODS: The genome of fosfomycin-resistant Escherichia coli strain YD786 was sequenced. Homologues of FosA6 were identified through BLAST searches. FosA6 and FosA(ST258) were purified and characterized using a steady-state kinetic approach. Inhibition of FosA activity was examined with sodium phosphonoformate. RESULTS: Plasmid-encoded glutathione-S-transferase (GST) FosA6 conferring high-level fosfomycin resistance was identified in a CTX-M-2-producing E. coli clinical strain at a US hospital. fosA6 was carried on a self-conjugative, 69 kb IncFII plasmid. The DeltalysR fosA6-DeltayjiR_1 fragment, located between IS10R and DeltaIS26, was nearly identical to those on the chromosomes of some Klebsiella pneumoniae strains (MGH78578, PMK1 and KPPR1). FosA6 shared >99% identity with chromosomally encoded FosA(PMK1) in K. pneumoniae of various STs and 98% identity with FosA(ST258), which is commonly found in K. pneumoniae clonal complex (CC) 258 including ST258. FosA6 and FosA(ST258) demonstrated robust GST activities that were comparable to each other. Sodium phosphonoformate, a GST inhibitor, reduced the fosfomycin MICs by 6- to 24-fold for K. pneumoniae and E. coli strains carrying fosA genes on the chromosomes and plasmids, respectively. CONCLUSIONS: fosA6, probably captured from the chromosome of K. pneumoniae, conferred high-level fosfomycin resistance in E. coli. FosA6 functioned as a GST and inactivated fosfomycin efficiently. K. pneumoniae may serve as a reservoir of fosfomycin resistance for E. coli. PMID- 27261268 TI - Sulphonamide resistance associated with integron derivative Tn6326 in Actinotignum schaalii. PMID- 27261269 TI - Important prognostic significance of lymph node density in patients with node positive oral tongue cancer. AB - BACKGROUND: Lymph node density (LND) has been described as a prognostic factor for survival in patients with head and neck squamous cell carcinoma, particularly of the oral cavity. The aim of this study was to determine the prognostic significance of LND in patients with node positive oral tongue squamous cell carcinoma (OTSCC). METHODS: Patients with pathological node positive OTSCC were identified in a retrospective review of prospectively collected data. The optimal cut-point for LND was determined using the minimum P-value method and the log rank test. The impact of this LND cut-point on time to disease progression and overall survival was determined. RESULTS: In 72 patients with OTSCC, an LND of 14.3% was found to have the greatest separation using the log-rank test (P < 0.001). LND <=14.3% was predicted for longer time to disease progression with a median time of 73 months compared to 9.4 months in patients with an LND >14.3% (hazard ratio: 3.43; 95% confidence interval: 1.76-6.70; P < 0.001). LND was also a significant predictor of overall survival with a median overall survival with LND <=14.3% of 82.3 months, compared with 14.7 months in patients with an LND >14.3% (hazard ratio: 3.28; 95% confidence interval: 1.61-6.68; P = 0.001). Patients with an LND >14.3% experienced a higher rate of regional recurrence. CONCLUSION: Our findings confirm the prognostic significance of LND in patients with node positive OTSCC, with a similar LND cut-point value to other published series. Improving regional control in these high-risk patients may improve outcome. PMID- 27261271 TI - A Web-Based Platform for Patients With Osteoarthritis of the Hip and Knee: A Pilot Study. AB - BACKGROUND: Chronic conditions are the leading cause of disability throughout the world and the most expensive problem facing the health care systems. One such chronic condition is osteoarthritis (OA), a frequent cause of major disability. OBJECTIVE: To describe the effect on joint pain for the first users of a newly developed Web-based osteoarthritis self-managing program, Joint Academy, and to examine whether these patients would recommend other OA patients to use the program. METHODS: Patients with clinically established knee or hip OA according to national and international guidelines were recruited from an online advertisement. A trained physiotherapist screened the eligible patients by scrutinizing their answers to a standardized questionnaire. The 6-week program consisted of eight 2- to 5-minute videos with lectures about OA, effects of physical activity, self-management, and coping strategies. In addition, exercises to improve lower extremity physical function were introduced in daily video activities. During the course of the program, communication between physiotherapist and patients was based on an asynchronous chat. After 6 weeks, patients were able to continue without support from the physiotherapist. Patients reported their current pain weekly by using a numeric rating scale (range 0-10; 0=no pain, 10=worst possible pain) as long as they were in the program. In addition, after 6 weeks patients answered the question "What is the probability that you would recommend Joint Academy to a friend?" RESULTS: The eligible cohort consisted of 53 individuals (39 women; body mass index: mean 27, SD 5; age: mean 57, SD 14 years). With the continued use of the program, patients reported a constant change in pain score from mean 5.1 (SD 2.1) at baseline to mean 3.6 (SD 2.0) at week 12. Six patients participated for 30 weeks (mean 3.2, SD 2.1). Overall, the patients would highly recommend Joint Academy to other OA patients, suggesting that the platform may be useful for at least some in the vast OA population. CONCLUSIONS: Joint Academy, a Web-based platform for OA therapy, has the potential to successfully deliver individualized online treatment to many patients with OA that presently lack access to treatment. PMID- 27261270 TI - VBP15, a novel dissociative steroid compound, reduces NFkappaB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis. AB - OBJECTIVE AND DESIGN: The goal of this study was to assess the capacity of VBP15, a dissociative steroidal compound, to reduce pro-inflammatory cytokine expression in vitro, to reduce symptoms of colitis in the trinitrobenzene sulfonic acid induced murine model, and to assess the effect of VBP15 on growth stunting in juvenile mice. MATERIALS: In vitro studies were performed in primary human intestinal epithelial cells. Colitis was induced in mice by administering trinitrobenzene sulfonic acid. Growth stunting studies were performed in wild type outbred mice. TREATMENT: Cells were treated with VBP15 or prednisolone (10 MUM) for 24 h. Mice were subjected to 3 days of VBP15 (30 mg/kg) or prednisolone (30 mg/kg) in the colitis study. In the growth stunting study, mice were subjected to VBP15 (10, 30, 45 mg/kg) or prednisolone (10 mg/kg) for 5 weeks. METHODS: Cytokines were measured by PCR and via Luminex. Colitis symptoms were evaluated by assessing weight loss, intestinal blood, and stool consistency. Growth stunting was assessed using an electronic caliper. RESULTS: VBP15 significantly reduced the in vitro production of CCL5 (p < 0.001) IL-6 (p < 0.001), IL-8 (p < 0.05) and reduced colitis symptoms (p < 0.05). VBP15 caused less growth stunting than prednisolone (p < 0.001) in juvenile mice. CONCLUSION: VBP15 may reduce symptoms of IBD, while decreasing or avoiding detrimental side effects. PMID- 27261272 TI - Vegetarian diets and gut microbiota: important shifts in markers of metabolism and cardiovascular disease. AB - Vegetarian diets have been associated with a lower incidence of several chronic diseases. The benefits of plant-based diets are related mainly to the improvement of metabolic parameters that can indicate risk for such diseases. Some metabolic factors, such as oxidative balance, lipid profile, and glucose homeostasis, can be improved directly by diet, but paradoxically, some characteristics of vegetarian diets may promote a negative scenario that increases the risk of certain chronic diseases. Additionally, many benefits of a vegetarian diet are mediated by the gut microbiota, members of which not only have taxonomic and functional differences but also produce diverse, specific metabolites that vary according to whether the host consumes an omnivorous or a vegetarian diet. This review examines the modulation of human metabolism and gut microbiota by vegetarian and omnivorous dietary patterns and explores how this modulation may affect the risk of cardiovascular disease. PMID- 27261273 TI - Chromium supplements for glycemic control in type 2 diabetes: limited evidence of effectiveness. AB - Some adults with type 2 diabetes mellitus (T2DM) believe that chromium-containing supplements will help control their disease, but the evidence is mixed. This narrative review examines the efficacy of chromium supplements for improving glycemic control as measured by decreases in fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c). Using systematic search criteria, 20 randomized controlled trials of chromium supplementation in T2DM patients were identified. Clinically meaningful treatment goals were defined as an FPG of <=7.2 mmol/dL, a decline in HbA1c to <=7%, or a decrease of >=0.5% in HbA1c. In only a few randomized controlled trials did FPG (5 of 20), HbA1c (3 of 14), or both (1 of 14) reach the treatment goals with chromium supplementation. HbA1c declined by >=0.5% in 5 of 14 studies. On the basis of the low strength of existing evidence, chromium supplements have limited effectiveness, and there is little rationale to recommend their use for glycemic control in patients with existing T2DM. Future meta-analyses should include only high-quality studies with similar forms of chromium and comparable inclusion/exclusion criteria to provide scientifically sound recommendations for clinicians. PMID- 27261274 TI - The placenta: the forgotten essential organ of iron transport. AB - Optimal iron nutrition in utero is essential for development of the fetus and helps establish birth iron stores adequate to sustain growth in early infancy. In species with hemochorial placentas, such as humans and rodents, iron in the maternal circulation is transferred to the fetus by directly contacting placental syncytiotrophoblasts. Early kinetic studies provided valuable data on the initial uptake of maternal transferrin, an iron-binding protein, by the placenta. However, the remaining steps of iron trafficking across syncytiotrophoblasts and through the fetal endothelium into the fetal blood remain poorly characterized. Over the last 20 years, identification of transmembrane iron transporters and the iron regulatory hormone hepcidin has greatly expanded the knowledge of cellular iron transport and its regulation by systemic iron status. In addition, emerging human and animal data demonstrating comprised fetal iron stores in severe maternal iron deficiency challenge the classic dogma of exclusive fetal control over the transfer process and indicate that maternal and local signals may play a role in regulating this process. This review compiles current data on the kinetic, molecular, and regulatory aspects of placental iron transport and considers new questions and knowledge gaps raised by these advances. PMID- 27261275 TI - Chemopreventive properties of 3,3'-diindolylmethane in breast cancer: evidence from experimental and human studies. AB - Diet is a modifiable factor associated with the risk of several cancers, with convincing evidence showing a link between diet and breast cancer. The role of bioactive compounds of food origin, including those found in cruciferous vegetables, is an active area of research in cancer chemoprevention. This review focuses on 3,3'-diindolylmethane (DIM), the major bioactive indole in crucifers. Research of the cancer-preventive activity of DIM has yielded basic mechanistic, animal, and human trial data. Further, this body of evidence is largely supported by observational studies. Bioactive DIM has demonstrated chemopreventive activity in all stages of breast cancer carcinogenesis. This review describes current evidence related to the metabolism and mechanisms of DIM involved in the prevention of breast cancer. Importantly, this review also focuses on current evidence from human observational and intervention trials that have contributed to a greater understanding of exposure estimates that will inform recommendations for DIM intake. PMID- 27261276 TI - Lipopolysaccharide-Induced CD300b Receptor Binding to Toll-like Receptor 4 Alters Signaling to Drive Cytokine Responses that Enhance Septic Shock. AB - Receptor CD300b is implicated in regulating the immune response to bacterial infection by an unknown mechanism. Here, we identified CD300b as a lipopolysaccharide (LPS)-binding receptor and determined the mechanism underlying CD300b augmentation of septic shock. In vivo depletion and adoptive transfer studies identified CD300b-expressing macrophages as the key cell type augmenting sepsis. We showed that CD300b, and its adaptor DAP12, associated with Toll-like receptor 4 (TLR4) upon LPS binding, thereby enhancing TLR4-adaptor MyD88- and TRIF-dependent signaling that resulted in an elevated pro-inflammatory cytokine storm. LPS engagement of the CD300b-TLR4 complex led to the recruitment and activation of spleen tyrosine kinase (Syk) and phosphatidylinositol-4,5 bisphosphate 3-kinase (PI3K). This resulted in an inhibition of the ERK1/2 protein kinase- and NF-kappaB transcription factor-mediated signaling pathways, which subsequently led to a reduced interleukin-10 (IL-10) production. Collectively, our data describe a mechanism of TLR4 signaling regulated by CD300b in myeloid cells in response to LPS. PMID- 27261278 TI - Analysis of polycyclic aromatic hydrocarbons (PAHs) in Lebanese surficial sediments: A focus on the regions of Tripoli, Jounieh, Dora, and Tyre. AB - This paper aims to identify the concentrations of PAHs in the sediments of four coastal zones in Lebanon and determine their possible sources and effects. For each region (Tripoli, Jounieh, Dora, and Tyre), sampling, lyophilization, Soxhlet extraction, rotary evaporation, and gas chromatography were performed on 11, 10, 7, and 11 samples, respectively. The total PAHs concentrations ranged from 1.22 to 731.93MUg/kg dry weight. The lowest concentrations were found in Tyre and the highest in Dora and Jounieh. The level of PAHs was classified as low to moderate and their source was mainly pyrogenic. PMID- 27261279 TI - The impact of onsite wastewater disposal systems on groundwater in areas inundated by Hurricane Sandy in New York and New Jersey. AB - Coastal onsite wastewater disposal systems (OWDS) were inundated by Hurricane Sandy's storm tide. This study compares the shallow groundwater quality (nutrients, pharmaceuticals, and hormones) downgradient of OWDS before and after Hurricane Sandy, where available, and establishes a baseline for wastewater influence on groundwater in coastal communities inundated by Hurricane Sandy. Nutrients and contaminants of emerging concern (CECs) were detected in shallow groundwater downgradient of OWDS in two settings along the New Jersey and New York coastlines: 1) a single, centralized OWDS in a park; and 2) multiple OWDS (cesspools) in low-density residential and mixed-use/medium density residential areas. The most frequently detected pharmaceuticals were lidocaine (40%), carbamazepine (36%), and fexofenadine, bupropion, desvenlafaxine, meprobamate, and tramadol (24-32%). Increases in the number and total concentration of pharmaceuticals after Hurricane Sandy may reflect other factors (seasonality, usage) besides inundation, and demonstrate the importance of analyzing for a wide variety of CECs in regional studies. PMID- 27261277 TI - Store-Operated Ca(2+) Entry in Follicular T Cells Controls Humoral Immune Responses and Autoimmunity. AB - T follicular helper (Tfh) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (Tfr) cells limit the GC reaction. Store-operated Ca(2+) entry (SOCE) through Ca(2+) release-activated Ca(2+) (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Conditional deletion of Stim1 and Stim2 genes in T cells abolished SOCE and strongly reduced antibody-mediated immune responses following viral infection caused by impaired differentiation and function of Tfh cells. Conversely, aging Stim1Stim2-deficient mice developed humoral autoimmunity with spontaneous autoantibody production due to abolished Tfr cell differentiation in the presence of residual Tfh cells. Mechanistically, SOCE controlled Tfr and Tfh cell differentiation through NFAT-mediated IRF4, BATF, and Bcl-6 transcription-factor expression. SOCE had a dual role in controlling the GC reaction by regulating both Tfh and Tfr cell differentiation, thus enabling protective B cell responses and preventing humoral autoimmunity. PMID- 27261280 TI - Can environmental DNA (eDNA) be used for detection and monitoring of introduced crab species in the Baltic Sea? AB - The need to detect and monitor introduced marine species has increased with the increasing number of marine invasions. To complement standard detection and monitoring techniques, new approaches using environmental DNA (eDNA) have recently been developed. However, most of the eDNA work has focused on vertebrate species in spatially limited freshwater habitats while benthic invertebrates in coastal environments have received much less attention. Here, we evaluated the suitability of the eDNA approach for detecting benthic, hard-shelled, crustacean mud crab species in a brackish water environment. We demonstrated for the first time that eDNA from an introduced mud crab Rhithropanopeus harrisii can be successfully amplified in aquarium water samples and detected in the brackish water environment. However, the detection rate was rather low. This suggests that in contrast to freshwater vertebrates, it may be more challenging to develop a highly sensitive eDNA method for detecting crustacean species in a marine environment. PMID- 27261324 TI - Using Electronic Medical Records to Assess the Effectiveness of Pharmacotherapy in Pain: A Review of Recent Observational Studies. AB - Pain disorders affect a large number of individuals throughout the world and are costly. Although randomized clinical trials assess the efficacy (i.e., how well treatments work in controlled settings) of pain pharmacotherapy, clinical trials do not assess effectiveness (i.e., how well treatments work in real-world settings). The number of observational studies that use real-world data to assess the effectiveness of medications is increasing rapidly in many disease areas. It is important for clinicians to understand how real-world data may be used to assess the effectiveness of medications. This paper aims to review the current body of literature assessing the effectiveness of pain pharmacotherapy using medical records. To do this, a literature search was conducted to identify papers published between January 2013 and September 2015 that examined the effectiveness of pain pharmacotherapy using electronic medical records. The search found only three papers meeting these criteria, which were described, reviewed, and critiqued in this paper. Electronic medical records are an underutilized source of data to assess pain outcomes in real-world settings. Although there are many methodological challenges in using these data, there is also great opportunity to impact clinical practice and explore the real-world effectiveness of pharmacotherapy used in pain management. PMID- 27261325 TI - Diverting ileostomy during primary debulking surgery for ovarian cancer: Associated factors and postoperative outcomes. AB - OBJECTIVE: To examine the use, as well as postoperative and long-term oncologic outcomes of diverting loop ileostomy (DI) during primary debulking surgery (PDS) for ovarian cancer. METHODS: Patients with stage II-IV ovarian, fallopian tube, or primary peritoneal carcinoma who underwent colon resection during PDS from 1/2005-1/2014 were identified. Demographic and clinical data were analyzed. RESULTS: Of 331 patients, 320 (97%) had stage III/IV disease and 278 (84%) had disease of high-grade serous histology. Forty-four (13%) underwent a DI. There were no significant differences in age, comorbidity index, smoking status, serum albumin, or attending surgeon between the DI and non-DI groups. Operative time (OR=1.21; 95% CI, 1.03-1.42; p=0.02) and length of rectosigmoid resection (OR=1.04; 95% CI, 1.01-1.08; p=0.02) were predictors of DI on multivariable analysis. The overall anastomotic leak rate was 6%. A comparison of groups (DI vs non-DI) showed no significant differences in major complications (30% vs 23%; p=0.41), anastomotic leak rate (5% vs 7%; p=0.60), hospital length of stay (10 vs 9days; p=0.25), readmission rate (23% vs 17%; p=0.33), or interval to postoperative chemotherapy (41 vs 40days; p=0.20), respectively. Ileostomy reversal was successful in 89% of patients. Median follow-up was 52.6months. There were no differences in median progression-free (17.9 vs 18.6months; p=0.88) and overall survival (48.7 vs 63.8months; p=0.25) between the groups. CONCLUSIONS: In patients undergoing PDS, those with longer operative time and greater length of rectosigmoid resection more commonly underwent DI. DI does not appear to compromise postoperative outcomes or long-term survival. PMID- 27261326 TI - Lymphovascular space invasion in uterine corpus cancer: What is its prognostic significance in the absence of lymph node metastases? AB - OBJECTIVE: Lymphovascular space invasion (LVSI) is a poor prognostic indicator in uterine cancer, primarily due to its association with lymph node metastases. We sought to determine if LVSI provides any prognostic information for uterine cancer subjects in the absence of nodal disease. METHODS: A retrospective review was performed using a database of women treated for uterine cancer at MUSC from 2005 to 2012. Subjects with negative nodes after complete staging were identified. Multiple regression modeling was used to adjust for demographic and histopathologic covariates. The C-index was calculated for models of survival that included LVSI and those that did not. Competing risks analysis was conducted to examine factors associated with time to recurrence. RESULTS: Two hundred and five subjects were completely staged and had negative nodes, 24 with LVSI and 181 without. Factors significantly associated with survival included age, race, stage, grade, histology, and LVSI. Regression models for recurrence-free survival (RFS) and overall survival (OS) had similar C-indices regardless of whether LVSI was included. Competing risks analysis confirmed no significant difference in time to recurrence for subjects with LVSI compared to those without, after adjusting for other prognostic factors (P=0.53). CONCLUSIONS: LVSI is associated with shorter recurrence-free and overall survival in uterine cancer subjects with negative lymph nodes. However, after adjusting for other prognostic factors, LVSI status does not provide additional prognostic information. This finding suggests that recurrence-free and overall survival for uterine cancer patients with negative lymph nodes can be estimated without factoring in LVSI. PMID- 27261327 TI - Endosalpingiosis: More than just an incidental finding at the time of gynecologic surgery? AB - OBJECTIVE: To describe the clinical characteristics of patients with endosalpingiosis (ES) and examine its association with endometriosis and gynecologic malignancies. METHODS: We queried the medical record for patients who underwent gynecologic surgery (Gynecologic Surgery Cohort (GSC), n=58,161) from 1998 to 2013 at a single institution for the presence of "endosalpingiosis" (ES). Demographic and clinical characteristics were collected for patients with pathologically confirmed ES (n=838). Within GSC, we compared the frequency of endometriosis and gynecologic malignancies with and without ES. We estimated the expected distribution of ovarian cancer subtypes using cases from the New England Case Control Study (NECC). We used chi-square tests to test for significant differences in frequency distributions and unconditional logistic regression to calculate multivariate odds ratios for the association between ES and ovarian cancer subtypes. RESULTS: We observed concurrent endometriosis (p<0.0001), uterine cancer (p<0.0001), and ovarian cancer (p<0.0001) more frequently in women with ES. Women from the GSC with ES and ovarian cancer were more likely to have serous borderline (OR=10.2, 95% CI=5.1-20.7), clear cell (OR=3.0, 95% CI=1.1 8.0), and invasive mucinous tumors (OR=5.0, 95% CI=1.5-16.6) as compared to ovarian cancer cases from the NECC without ES, after accounting for age, race, menopausal status, parity, tubal ligation, and endometriosis. CONCLUSION: Women with ES are more likely to also be diagnosed with endometriosis, uterine, and ovarian cancers. Further study is needed to understand these associations so we may appropriately counsel patients with ES diagnosed at time of gynecologic surgery. PMID- 27261329 TI - Pityriasis lichenoides chronica responds to minocycline in three patients. PMID- 27261328 TI - Targeting Intrinsic and Extrinsic Vulnerabilities for the Treatment of Multiple Myeloma. AB - Multiple myeloma (MM) is a malignant plasma cell disorder, clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. Over the past decade, MM therapy is significantly improved by the introduction of novel therapeutics such as immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), monoclonal antibodies (daratumumab and elotuzumab), histone deacetylase (HDAC) inhibitors (Panobinostat). The clinical success of these agents has clearly identified vulnerabilities intrinsic to the MM cell, as well as targets that emanate from the tumor microenvironment. Despite these significant improvements, MM remains incurable due to the development of drug resistance. This perspective will discuss more recent strategies which take advantage of multiple targets within the proteome recycling pathway, chromatin remodeling, and disruption of nuclear export. In addition, we will review the development of strategies designed to block opportunistic survival signaling that occurs between the MM cell and the tumor microenvironment including strategies for inhibiting myeloma induced immune suppression. It has become clear that MM tumors continue to evolve on therapy leading to drug resistance. It will be important to understand the emerging drug resistant mechanisms and additional vulnerabilities that occur due to the development of clinical resistance. J. Cell. Biochem. 118: 15-25, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27261330 TI - Serum Magnesium Levels and Hospitalization and Mortality in Incident Peritoneal Dialysis Patients: A Cohort Study. AB - BACKGROUND: Prior studies have shown the association of low serum magnesium levels with adverse health outcomes in patients undergoing hemodialysis. There is a paucity of such studies in patients undergoing peritoneal dialysis (PD). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 10,692 patients treated with PD from January 1, 2007, through December 31, 2011, in facilities operated by a single large dialysis organization in the United States. PREDICTOR: Baseline serum magnesium levels, examined as 5 categories (<1.8, 1.8-<2.0, 2.0-<2.2 [reference], 2.2-<2.4, and >=2.4mg/dL). OUTCOMES: Time to first hospitalization and time to death using competing-risks regression models. RESULTS: The distribution of baseline serum magnesium levels in the cohort was <1.8mg/dL, 1,928 (18%); 1.8 to <2.0mg/dL, 2,204 (21%); 2.0 to <2.2mg/dL, 2,765 (26%); 2.2 to <2.4mg/dL, 1,765 (16%); and >=2.4mg/dL, 2,030 (19%). Of 10,692 patients, 6,465 (60%) were hospitalized at least once and 1,392 (13%) died during follow-up (median, 13; IQR, 7-23 months). Baseline serum magnesium level < 1.8mg/dL was associated with higher risk for hospitalization and all-cause mortality after adjustment for demographic and clinical characteristics (adjusted HRs of 1.23 [95% CI, 1.14-1.33] and 1.21 [95% CI, 1.03-1.42], respectively). The higher risk for hospitalization persisted upon adjustment for laboratory variables, whereas that for all-cause mortality was attenuated to a nonsignificant level. The greatest risk for hospitalization was in patients with low serum albumin levels (<3.5g/dL; P for interaction < 0.001). LIMITATIONS: Possibility of residual confounding by unmeasured variables cannot be excluded. CONCLUSIONS: Lower serum magnesium levels may be associated with higher risk for hospitalization in incident PD patients, particularly those with hypoalbuminemia. Additional studies are needed to confirm these findings and investigate whether correction of hypomagnesemia reduces these risks. PMID- 27261332 TI - New Peptides Under the s(ORF)ace of the Genome. AB - Hundreds, perhaps thousands of previously unidentified functional small peptides could exist in most genomes, but these sequences have been generally overlooked. The discovery of genes encoding small peptides with important functions in different organisms has ignited the interest in these sequences and led to an increasing amount of effort towards their identification. Here, we review the advances, both computational and biochemical, that are leading the way in the discovery of putatively functional small open reading frame genes (smORFs), as well as the functional studies that have been carried out as a consequence of these searches. The evidence suggests that smORFs form a substantial part of our genomes, and that their encoded peptides could have a variety of important cellular functions. PMID- 27261331 TI - Dietary Guideline Adherence Index and Kidney Measures in the Framingham Heart Study. AB - BACKGROUND: No observational studies have directly considered dietary guidelines when examining the prospective association between dietary intake and kidney measures. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We examined participants who attended examinations 7 (1998-2001) and 8 (2005-2008) in the Framingham Offspring Cohort. PREDICTORS: Individual components of Dietary Guidelines for Americans Adherence Index (DGAI) that reflect adherence to key dietary recommendations based on the 2005 guideline. OUTCOMES & MEASURES: The primary outcome was incident low estimated glomerular filtration rate (eGFR) at follow-up after exclusion of prevalent low eGFR at baseline. Low eGFR was defined as serum creatinine-based eGFR<60mL/min/1.73m2. RESULTS: Among 1,822 participants (mean age, 59.4 years; 54.6% women), 181 incident cases of low eGFR were identified. After adjustment for potential confounders, compared to optimal adherence to meat and legume recommendations, low adherence was associated with higher odds of incident low eGFR (P for trend = 0.01); ORs in the lowest and intermediate adherence categories were 2.98 (95% CI, 1.13-7.92) and 1.65 (95% CI, 1.02-2.66), respectively. Low adherence to dairy product recommendations was also associated with higher odds of incident low eGFR compared to optimal adherence (P for trend = 0.03); ORs in the lowest and intermediate adherence categories were 1.98 (95% CI, 1.03-3.82) and 1.59 (95% CI, 0.81-3.11), respectively. In addition, low adherence to meat and legume recommendations was associated with rapid eGFR decline (P for trend = 0.01), and low adherence to dairy product recommendations was associated with rapid eGFR decline (P for trend = 0.01) and incident albuminuria (P for trend = 0.03). LIMITATIONS: The DGAI was developed based on the 2005 Dietary Guidelines for Americans. CONCLUSIONS: Better adherence to dietary recommendations for both meat and legumes and dairy products was associated with lower risk for developing adverse kidney measures. PMID- 27261333 TI - Delivery of LLKKK18 loaded into self-assembling hyaluronic acid nanogel for tuberculosis treatment. AB - Tuberculosis (TB), a disease caused by the human pathogen Mycobacterium tuberculosis, recently joined HIV/AIDS on the top rank of deadliest infectious diseases. Low patient compliance due to the expensive, long-lasting and multi drug standard therapies often results in treatment failure and emergence of multi drug resistant strains. In this scope, antimicrobial peptides (AMPs) arise as promising candidates for TB treatment. Here we describe the ability of the exogenous AMP LLKKK18 to efficiently kill mycobacteria. The peptide's potential was boosted by loading into self-assembling Hyaluronic Acid (HA) nanogels. These provide increased stability, reduced cytotoxicity and degradability, while potentiating peptide targeting to main sites of infection. The nanogels were effectively internalized by macrophages and the peptide presence and co localization with mycobacteria within host cells was confirmed. This resulted in a significant reduction of the mycobacterial load in macrophages infected in vitro with the opportunistic M. avium or the pathogenic M. tuberculosis, an effect accompanied by lowered pro-inflammatory cytokine levels (IL-6 and TNF alpha). Remarkably, intra-tracheal administration of peptide-loaded nanogels significantly reduced infection levels in mice infected with M. avium or M. tuberculosis, after just 5 or 10 every other day administrations. Considering the reported low probability of resistance acquisition, these findings suggest a great potential of LLKKK18-loaded nanogels for TB therapeutics. PMID- 27261334 TI - l-DOPA as a small molecule surrogate to promote angiogenesis and prevent dexamethasone-induced ischemia. AB - The foreign body response to implantable biosensors has been successfully countered through the use of corticosteroids, such as dexamethasone. However, while controlling inflammation, dexamethasone also decreases angiogenesis, which may lead to delayed analyte readings. The concurrent application of VEGF with dexamethasone increases angiogenesis, but VEGF has physical stability issues and is not cost-effective. The use of l-DOPA, a small molecule drug shown to up regulate VEGF in the Parkinsonian brain, can potentially resolve these issues by substituting for VEGF. In this work, l-DOPA was used for the first time as a pro angiogenic agent to counteract dexamethasone-induced ischemia. Angiogenesis was modeled using the CAM assay and changes in blood vessel formation were recorded with both manual and digital techniques. As expected, dexamethasone reduced blood vessel formation in the CAM. Application of l-DOPA, on the other hand, increased blood vessel formation when dexamethasone and l-DOPA were administered simultaneously. This novel finding suggests the utility of l-DOPA in the field of implantable medical devices, such as biosensors, as well as tissue engineering applications where both a vascularized tissue environment and control of tissue response is desired. PMID- 27261335 TI - RGD liposome-protamine-siRNA (LPR) nanoparticles targeting PAX3-FOXO1 for alveolar rhabdomyosarcoma therapy. AB - Alveolar rhabdomyosarcoma (ARMS) are aggressive soft tissue tumors harboring specific fusion transcripts, notably PAX3-FOXO1 (P3F). Current therapy concepts result in unsatisfactory survival rates making the search for innovative approaches necessary: targeting PAX3-FOXO1 could be a promising strategy. In this study, we developed integrin receptor-targeted Lipid-Protamine-siRNA (LPR) nanoparticles using the RGD peptide and validated target specificity as well as their post-silencing effects. We demonstrate that RGD-LPRs are specific to ARMS in vitro and in vivo. Loaded with siRNA directed against the breakpoint of P3F, these particles efficiently down regulated the fusion transcript and inhibited cell proliferation, but did not induce substantial apoptosis. In a xenograft ARMS model, LPR nanoparticles targeting P3F showed statistically significant tumor growth delay as well as inhibition of tumor initiation when injected in parallel with the tumor cells. These findings suggest that RGD-LPR targeting P3F are promising to be highly effective in the setting of minimal residual disease for ARMS. PMID- 27261336 TI - Insights into zinc and cadmium biology in the nematode Caenorhabditis elegans. AB - Zinc is an essential metal that is involved in a wide range of biological processes, and aberrant zinc homeostasis is implicated in multiple human diseases. Cadmium is chemically similar to zinc, but it is a nonessential environmental pollutant. Because zinc deficiency and excess are deleterious, animals require homeostatic mechanisms to maintain zinc levels in response to dietary fluctuations. The nematode Caenorhabditis elegans is emerging as a powerful model system to investigate zinc trafficking and homeostasis as well as cadmium toxicity. Here we review genetic and molecular studies that have combined to generate a picture of zinc homeostasis based on the transcriptional control of zinc transporters in intestinal cells. Furthermore, we summarize studies of cadmium toxicity that reveal intriguing parallels with zinc biology. PMID- 27261337 TI - Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus. AB - OBJECTIVE: Since the publication of the Asia-Pacific consensus on gastro oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. METHODS: A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. RESULTS: A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1 cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. CONCLUSIONS: These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia Pacific region. PMID- 27261339 TI - Robots in elder care: Some ethical questions. PMID- 27261342 TI - Letter From the Editor: The Mediastinum. PMID- 27261338 TI - Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. AB - OBJECTIVE: Today most patients with Lynch syndrome (LS) survive their first cancer. There is limited information on the incidences and outcome of subsequent cancers. The present study addresses three questions: (i) what is the cumulative incidence of a subsequent cancer; (ii) in which organs do subsequent cancers occur; and (iii) what is the survival following these cancers? DESIGN: Information was collated on prospectively organised surveillance and prospectively observed outcomes in patients with LS who had cancer prior to inclusion and analysed by age, gender and genetic variants. RESULTS: 1273 patients with LS from 10 countries were followed up for 7753 observation years. 318 patients (25.7%) developed 341 first subsequent cancers, including colorectal (n=147, 43%), upper GI, pancreas or bile duct (n=37, 11%) and urinary tract (n=32, 10%). The cumulative incidences for any subsequent cancer from age 40 to age 70 years were 73% for pathogenic MLH1 (path_MLH1), 76% for path_MSH2 carriers and 52% for path_MSH6 carriers, and for colorectal cancer (CRC) the cumulative incidences were 46%, 48% and 23%, respectively. Crude survival after any subsequent cancer was 82% (95% CI 76% to 87%) and 10-year crude survival after CRC was 91% (95% CI 83% to 95%). CONCLUSIONS: Relative incidence of subsequent cancer compared with incidence of first cancer was slightly but insignificantly higher than cancer incidence in patients with LS without previous cancer (range 0.94-1.49). The favourable survival after subsequent cancers validated continued follow-up to prevent death from cancer. The interactive website http://lscarisk.org was expanded to calculate the risks by gender, genetic variant and age for subsequent cancer for any patient with LS with previous cancer. PMID- 27261343 TI - Pathology of the Trachea and Central Bronchi. AB - A wide variety of disorders can affect the trachea and central bronchi. Computed tomography is the imaging modality of choice in the evaluation of tracheobronchial disease. Tracheobronchial abnormalities are sometimes incidentally detected on routine imaging or when imaging is performed for another reason. Abnormalities of the tracheobronchial tree, however, can be easily missed because they can be subtle. Furthermore, because symptoms in patients with tracheobronchial disorders often overlap symptoms of lung disease, radiologists may focus their attention on the lungs and overlook the tracheobronchial tree. In this article, we review a wide range of tracheobronchial diseases with emphasis on their computed tomographic appearances. PMID- 27261344 TI - Tracheal Diverticula. AB - Extraluminal paratracheal air bubbles are occasionally seen on computed tomography (CT) studies that include the thoracic inlet (ie, CT of the neck, of the cervical spine, and of the chest). In most cases, these paratracheal air bubbles are tracheal diverticula (TD), sometimes also referred to as tracheal pouch, tracheocele, and tracheogenic cyst. TD are most commonly seen at the right posterolateral aspect of the upper trachea at the level T1-T3. Because of their typical location and appearance, they are easily recognized and should not be confused with pneumomediastinum or other causes of air bubbles in the same region. This article describes the prevalence, possible pathophysiology, and associated complications of TD and illustrates the spectrum of their appearance on CT. PMID- 27261345 TI - Solid Tumors of the Mediastinum in Adults. AB - A wide spectrum of solid tumors can develop in the mediastinum of adults. Like for any other tumor evaluation, the location and morphology play equally important role for lesion characterization. Compartmentalizing the mediastinal masses greatly narrows the number of possible differential diagnosis. Cross sectional imaging mainly with computed tomography (CT) and magnetic resonance imaging (MRI) are the preferred modalities of choice as they can establish the presence, location and morphology of the lesion allowing to suggest a possible diagnosis. PMID- 27261346 TI - Cystic Lesions of the Mediastinum. AB - Cystic lesions are commonly seen in the mediastinum, and they may arise from virtually any organ. The vast majority of these lesions are benign and result in no symptoms. When large, cysts may produce symptoms related to compression of adjacent structures. The most common mediastinal cysts are pericardial and foregut duplication cysts. Both computed tomography and magnetic resonance are routinely used to evaluate these lesions. Although computed tomography offers superior spatial resolution, magnetic resonance is useful in differentiating cysts that contain proteinaceous material from solid lesions. Occasionally, cysts arise from solid lesions, such as thymoma or teratoma. Although cysts are alike in appearance, location helps narrowing the differential diagnoses. PMID- 27261347 TI - Pediatric Mediastinal Tumors and Tumor-Like Lesions. AB - This article reviews the imaging findings of pediatric mediastinal tumors and tumor-like lesions. The classification of the mediastinum is discussed with normal imaging appearance of the thymus in pediatric age group followed by a discussion on multiple mediastinal lesions in different compartments with emphasis on their imaging characteristics. PMID- 27261348 TI - Imaging of Pericardial Diseases. AB - Given the widespread use of cross-sectional imaging modalities, specifically multidetector computed tomography and magnetic resonance, to evaluate thoracic disease, the pericardium is frequently imaged. Knowledge of the normal appearance and anatomical boundaries is vital for radiologists to avoid confusion with more sinister pathology. A variety of disorders and diseases of the pericardium can bring a patient to clinical attention from inflammatory conditions, resulting in pericarditis and pericardial effusion, to malignancy. This article discusses the anatomy and conditions that affect the pericardium, emphasizing the role imaging plays in diagnosis and management. PMID- 27261349 TI - Mediastinal Imaging Pitfalls. AB - Potential pitfalls in the interpretation of diseases involving the mediastinum are seen when imaging with computed tomography and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography. These pitfalls can involve any mediastinal structure, including the mediastinal vessels, heart, lymph nodes, thymus, trachea, esophagus, and fat. Misinterpretation of normal variants or benign conditions as pathology can affect staging and alter treatment. After reading this review, the reader should be able to identify common mediastinal imaging pitfalls and apply ancillary measures to confirm the correct diagnosis and thus reach an accurate diagnosis to facilitate correct patient treatment. PMID- 27261350 TI - Radiation Effects in the Mediastinum and Surroundings: Imaging Findings and Complications. AB - Radiotherapy is one of the cornerstones for treatment of patients with cancer. Although advances in radiotherapy technology have considerably improved radiation delivery, potential adverse effects are still common. Postradiation changes to the mediastinum can include different structures such as the heart, great vessels, and esophagus. The purpose of the article was to illustrate the expected variety of changes to the mediastinum and adjacent lung resulting from external beam radiotherapy and radiotherapy-induced complications to the mediastinum and to discuss different radiotherapy delivery techniques. PMID- 27261351 TI - Pro-inflammatory cytokines, IL-1beta and TNF-alpha, produce persistent compromise in tonic immobility defensive behaviour in endotoxemia guinea-pigs. AB - AIM: Sepsis has been associated with acute behavioural changes in humans and rodents, which consists of a motivational state and an adaptive response that improve survival. However, the involvement of peripheral cytokines synthesized during systemic inflammation as modulators of the tonic immobility (TI) defensive behaviour remains a literature gap. Our purposes were to characterize the TI defensive behaviour in endotoxemia guinea-pigs at acute phase and after recovery from the initial inflammatory challenge. Furthermore, we investigated whether peri-aqueductal grey matter (PAG) exists as a brain structure related to this behaviour and also pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta, act at this mesencephalic nucleus. METHODS: Endotoxemia was induced by lipopolysaccharide (LPS) administration in guinea pigs. The parameters evaluated included TI defensive behaviour, survival, cytokines production, as well as neuronal activation and apoptosis in the PAG. RESULTS: Endotoxemia guinea-pigs exhibited a reduction in the duration of TI episodes, starting at 2 h after LPS administration and persisting throughout the experimental period evaluated over 7 days. Moreover, endotoxemia increased the c FOS immunoreactivity of neurones in the ventrolateral PAG (vlPAG), as well as the caspase-3 expression. The LPS microinjection into vlPAG reproduces the same compromise, that is a decrease in the duration of TI defensive behaviour, observed after the peripheral administration. The immunoneutralization against IL 1beta and TNF-alpha into vlPAG reverts all the effects produced by peripheral LPS administration. CONCLUSION: Our findings confirm that vlPAG is an important brain structure involved in the behavioural alterations induced by endotoxemia, possibly changing the neuronal activity caused by pro-inflammatory cytokines produced peripherally. PMID- 27261362 TI - Isolation, identification and oenological characterization of non-Saccharomyces yeasts in a Mediterranean island. AB - We isolated, identified and characterized yeast strains from grapes, and their fermented musts, sampled in the small island of Linosa, where there are no wineries and therefore the possibility of territory contamination by industrial strains is minimal. By traditional culture-dependent methods, we isolated 3805 colonies, distinguished by molecular methods in 17 different species. Five hundred and forty-four isolates were analysed for the main oenological characteristics such as fermentative vigour with and without sulphites, sugar consumption and production of alcohol, volatile acidity, hydrogen sulphide, glycerol and beta-glucosidase. This analysis identified Kluyveromyces marxianus (seldomly used in winemaking) as the most interesting candidate yeast for the production of innovative wines. SIGNIFICANCE AND IMPACT OF THE STUDY: In recent years, interest is growing for wine production by non-Saccharomyces yeasts, both in research and in the industry. This study describes the yeast population of the grapes in a small-secluded island in the Mediterranean Sea, useful site for the search of new strains. Evaluation of fundamental oenological characters identifies potential best yeasts to assay in experimental vinifications. We also describe, for the first time, 14 new colony morphologies on WL Nutrient Agar, culture medium used to monitor the yeast population dynamics. PMID- 27261363 TI - Cell adhesion during bullet motion in capillaries. AB - A numerical analysis is presented of cell adhesion in capillaries whose diameter is comparable to or smaller than that of the cell. In contrast to a large number of previous efforts on leukocyte and tumor cell rolling, much is still unknown about cell motion in capillaries. The solid and fluid mechanics of a cell in flow was coupled with a slip bond model of ligand-receptor interactions. When the size of a capillary was reduced, the cell always transitioned to "bullet-like" motion, with a consequent decrease in the velocity of the cell. A state diagram was obtained for various values of capillary diameter and receptor density. We found that bullet motion enables firm adhesion of a cell to the capillary wall even for a weak ligand-receptor binding. We also quantified effects of various parameters, including the dissociation rate constant, the spring constant, and the reactive compliance on the characteristics of cell motion. Our results suggest that even under the interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P selectin, which is mainly responsible for leukocyte rolling, a cell is able to show firm adhesion in a small capillary. These findings may help in understanding such phenomena as leukocyte plugging and cancer metastasis. PMID- 27261364 TI - Acetylation and succinylation contribute to maturational alterations in energy metabolism in the newborn heart. AB - Dramatic maturational changes in cardiac energy metabolism occur in the newborn period, with a shift from glycolysis to fatty acid oxidation. Acetylation and succinylation of lysyl residues are novel posttranslational modifications involved in the control of cardiac energy metabolism. We investigated the impact of changes in protein acetylation/succinylation on the maturational changes in energy metabolism of 1-, 7-, and 21-day-old rabbit hearts. Cardiac fatty acid beta-oxidation rates increased in 21-day vs. 1- and 7-day-old hearts, whereas glycolysis and glucose oxidation rates decreased in 21-day-old hearts. The fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD) and beta hydroxyacyl-CoA dehydrogenase (beta-HAD), were hyperacetylated with maturation, positively correlated with their activities and fatty acid beta-oxidation rates. This alteration was associated with increased expression of the mitochondrial acetyltransferase, general control of amino acid synthesis 5 like 1 (GCN5L1), since silencing GCN5L1 mRNA in H9c2 cells significantly reduced acetylation and activity of LCAD and beta-HAD. An increase in mitochondrial ATP production rates with maturation was associated with the decreased acetylation of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, a transcriptional regulator for mitochondrial biogenesis. In addition, hypoxia-inducible factor 1alpha, hexokinase, and phosphoglycerate mutase expression declined postbirth, whereas acetylation of these glycolytic enzymes increased. Phosphorylation rather than acetylation of pyruvate dehydrogenase (PDH) increased in 21-day-old hearts, accounting for the low glucose oxidation postbirth. A maturational increase was also observed in succinylation of PDH and LCAD. Collectively, our data are the first suggesting that acetylation and succinylation of the key metabolic enzymes in newborn hearts play a crucial role in cardiac energy metabolism with maturation. PMID- 27261365 TI - Outcome of pN0 Triple-Negative Breast Cancer with or without Lymph Node Irradiation: A Single Institution Experience. AB - The optimal management of patients with pathologically node-negative triple negative breast cancer (pN0 TNBC) remains unclear. We hypothesized that lymph node irradiation (LNI; internal mammary chain/periclavicular irradiation) had an impact on outcomes of pN0 TNBC. A cohort of 126 consecutive patients with pN0 TNBC treated between 2007 and 2010 at a single institute were included. All radiotherapy (breast/chest wall, +/-LNI) was delivered adjuvantly, following completion of surgery +/- chemotherapy. Tumors were reviewed and histologic features were described. Tissue microarrays were constructed and tumors were assessed by immunohistochemistry using antibodies against ER, PR, HER2, Ki-67, cytokeratins 5/6, 14, epidermal growth factor receptor and androgen receptor. Patients were divided into two groups for statistical analysis: LNI (LNI+) or no LNI (LNI-). We focused on disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS). Fifty-seven and 69 patients received or not LNI, respectively. Median age was 52 (range [25-76]) and 55 (range [29-79]) in LNI+ and LNI- group (p = 0.23). LNI was associated with larger tumors (p = 0.033), central/internal tumors (33 versus 4, p < 0.01) and more chemotherapy (86% versus 59.4% p < 0.01). The median follow-up was 53.5 months. The rate of first regional relapse (associated or not with distant relapse) was low in both groups. There was no difference in 4-year DFS (82.2% versus 89.9%; p = 0.266), MFS (87.0% versus 91.1%; p = 0.286) and OS (85.8% versus 89.9%; p = 0.322) between LNI+ and LNI- group, respectively. In univariate analysis, only clinical size (T >10 mm versus <=10 mm), histologic size (pT >10 mm versus <=10 mm) and grade 3 (versus grade 2) were found to be significantly associated with shorter DFS. Omission of LNI in patients with pN0 TNBC does not seem to result in poorer outcome. Further studies are needed to specifically evaluate LNI in pN0 TNBC with histologic grade 3 and/or (p)T >10 mm. PMID- 27261366 TI - Newborn screening and population carrier screening for cystic fibrosis: Two ends of the same rope. PMID- 27261367 TI - Ketamine abuse potential and use disorder. AB - Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine. However, the therapeutic value of ketamine to treat psychiatric disorders faces a major challenge that ketamine also owns significant reinforcing and toxic effects. Its abuse has posted severe harms on individuals and society. Disrupted learning and memory processing has long been related with ketamine use. It is hypothesized that ketamine blocks NMDA receptors on gamma aminobutyric acid (GABA) neurons inside the thalamic reticular nucleus, which leads to disinhibition of dopaminergic neurons and increased release of dopamine. Currently, there is no specific treatment for treating every ketamine patient presenting peripheral toxicity. Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs. Future research can continue to develop creative ways to investigate potential mechanism and treatments related to ketamine abuse that have posted severe individual and social harms. PMID- 27261370 TI - Parent Perspectives of Neonatal Intensive Care at the End-of-Life. AB - This descriptive qualitative study explored parent experiences related to their infant's neonatal intensive care unit (NICU) hospitalization, end-of-life care, and palliative care consultation. "Life and death in the NICU environment" emerged as the primary theme with the following categories: ups and downs of parenting in the NICU, decision-making challenges in the NICU, and parent support. Parents encountered challenges with areas for improvement for end-of life and palliative care in the NICU. Further research is necessary to understand barriers with integrating palliative care and curative care in the NICU, and how NICU care affects bereavement and coping outcomes after infant death. PMID- 27261371 TI - Upregulation of Thrombin/Matrix Metalloproteinase-1/Protease-Activated Receptor-1 Chain in Proliferative Diabetic Retinopathy. AB - PURPOSE: Selective proteolytic activation of protease-activated receptor-1 (PAR1) by thrombin and matrix metalloproteinase-1 (MMP-1) plays a central role in enhancing angiogenesis. We investigated the expression levels of thrombin, MMP-1, and PAR1 and correlated these levels with vascular endothelial growth factor (VEGF) in proliferative diabetic retinopathy (PDR). In addition, we examined the expression of PAR1 and thrombin in the retinas of diabetic rats and PAR1 in human retinal microvascular endothelial cells (HRMEC) following exposure to high glucose, the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and the hypoxia mimetic agent cobalt chloride (CoCl2). METHODS: Vitreous samples from 32 PDR and 23 nondiabetic patients, epiretinal membranes from 10 patients with PDR, retinas of rats, and HRMEC were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and Western blot analysis. An assay for in vitro cell migration angiogenesis was performed in HRMEC. RESULTS: In epiretinal membranes, PAR1 was expressed in vascular endothelial cells, CD45-expressing leukocytes, and myofibroblasts. ELISA and Western blot assays revealed significant increases in the expression levels of thrombin, MMP-1, and VEGF in vitreous samples from PDR patients compared to nondiabetic controls. Significant positive correlations were found between the levels of VEGF and the levels of thrombin (r = 0.41; p = 0.006) and MMP-1 (r = 0.66; p < 0.0001). Significant increases of cleaved PAR1 (approximately 50 kDa) and the proteolytically active thrombin (approximately 50 kDa) were detected in rat retinas after induction of diabetes. The proinflammatory cytokines IL-1beta and TNF-alpha, but not high-glucose and CoCl2, induced upregulation of cleaved PAR1 (approximately 30 kDa) in HRMEC. In addition, thrombin and MMP-1 induced VEGF in HRMEC and vorapaxar, a PAR1 inhibitor, inhibited thrombin-induced migration in HRMEC. CONCLUSIONS: Interactions among thrombin, MMP-1, PAR1, and VEGF might facilitate angiogenesis in PDR. PMID- 27261369 TI - Modeling simple repeat expansion diseases with iPSC technology. AB - A number of human genetic disorders, including Huntington's disease, myotonic dystrophy type 1, C9ORF72 form of amyotrophic lateral sclerosis and several spinocerebellar ataxias, are caused by the expansion of various microsatellite sequences in single implicated genes. The neurodegenerative and neuromuscular nature of the repeat expansion disorders considerably limits the access of researchers to appropriate cellular models of these diseases. This limitation, however, can be overcome by the application of induced pluripotent stem cell (iPSC) technology. In this paper, we review the current knowledge on the modeling of repeat expansion diseases with human iPSCs and iPSC-derived cells, focusing on the disease phenotypes recapitulated in these models. In subsequent sections, we provide basic practical knowledge regarding iPSC generation, characterization and differentiation into neurons. We also cover disease modeling in iPSCs, neuronal stem cells and specialized neuronal cultures. Furthermore, we also summarize the therapeutic potential of iPSC technology in repeat expansion diseases. PMID- 27261372 TI - High Quality Independent From a Donor: Human Amniotic Fluid Derived Stem Cells-A Practical Analysis Based on 165 Clinical Cases. AB - The aim of the study was to extend the potential use of human stem cells isolated from amniotic fluid in medical applications by confirming their high homogeneity and quality. Amniotic fluid samples were collected during amniocentesis from 165 women during pregnancy. The proliferation rate, clonogenicity, karyotype, aging process, pluripotent cell markers, expression of surface markers, and the potential to differentiate into adipose, bone and cartilage cells of hAFSCs were analyzed. Obtained results revealed that mesenchymal stem cells could be derived successfully from amniotic fluid, which exhibit properties comparable with MSCs of other origins. It is the first study, in which such a large group of patients was involved. Comprehensive statistical and biological analysis were conducted some of which clearly being innovative in relation to human amniotic fluid derived stem cells. J. Cell. Biochem. 118: 116-126, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27261368 TI - Evolution of the archaeal and mammalian information processing systems: towards an archaeal model for human disease. AB - Current evolutionary models suggest that Eukaryotes originated from within Archaea instead of being a sister lineage. To test this model of ancient evolution, we review recent studies and compare the three major information processing subsystems of replication, transcription and translation in the Archaea and Eukaryotes. Our hypothesis is that if the Eukaryotes arose within the archaeal radiation, their information processing systems will appear to be one of kind and not wholly original. Within the Eukaryotes, the mammalian or human systems are emphasized because of their importance in understanding health. Biochemical as well as genetic studies provide strong evidence for the functional similarity of archaeal homologs to the mammalian information processing system and their dissimilarity to the bacterial systems. In many independent instances, a simple archaeal system is functionally equivalent to more elaborate eukaryotic homologs, suggesting that evolution of complexity is likely an central feature of the eukaryotic information processing system. Because fewer components are often involved, biochemical characterizations of the archaeal systems are often easier to interpret. Similarly, the archaeal cell provides a genetically and metabolically simpler background, enabling convenient studies on the complex information processing system. Therefore, Archaea could serve as a parsimonious and tractable host for studying human diseases that arise in the information processing systems. PMID- 27261406 TI - Association between Florida's smoke-free policy and acute myocardial infarction by race: A time series analysis, 2000-2013. AB - INTRODUCTION: Racial disparities in acute myocardial infarctions (AMIs) are increasing over time. Previous studies have shown that the implementation of smoke-free policies is associated with reduced AMI rates. The objective of this study was to determine the association between smoke-free policy and AMI hospitalization rates and smoking by race. METHODS: Healthcare Cost and Utilization Project data from Florida from 2000-2013 were analyzed using interrupted time series analysis to determine the relationship between Florida's smoke-free restaurant and workplace laws and AMI among the total adult population (aged >=18years), by age, race, and gender. Behavioral Risk Factor Surveillance System data from Florida from 2000 to 2010 were analyzed using logistic regression to determine the association between policy and the adult smoking prevalence. RESULTS: After implementation of the smoke-free policy, no statistically significant associations between AMI hospitalization rates or smoking prevalence were detected in the total population. In the subgroup analysis, the policy was associated with declines in AMI hospitalization rates among non-Hispanic white adults aged 18-44years (beta=-0.001 per 10,000, p value=0.0083). No other relationships with AMI hospitalization rates and smoking prevalence were found in the subgroup analysis. CONCLUSIONS: More comprehensive smoke-free and tobacco control policies are needed to further reduce AMI hospitalization rates, particularly among minority populations. Further research is needed to understand and address how the implementation of smoke-free policies affects secondhand smoke exposure among racial and ethnic minorities. PMID- 27261407 TI - Correlates of physical activity in children and adolescents with physical disabilities: A systematic review. AB - BACKGROUND: The benefits of physical activity (PA) for children with disabilities are well documented, and children with physical disabilities (PD) are often less active than peers with other disability types. Various correlates associated with PA in children with PD have been identified in separate studies, and a thorough analysis of these correlates could aid in understanding and designing interventions that promote children with PD to be more physically active. The purpose of this systematic review was to provide a comprehensive summary of the correlates of PA in children with PD. METHOD: A systematic search using PubMed, CINAHL, Cochrane Library, PsychINFO, Eric, and EMbase was initiated in October 2014 to identify studies examining the correlates of PA in children with PD aged 6-18years. Two researchers independently screened studies, assessed their methodological quality, and extracted relevant data. The correlates were synthesized and further assessed semi-quantitatively. RESULTS: A total of 45 articles were included in the detailed review. Several modifiable physical, psychological, and environmental correlates were consistently and positively associated with PA in children with PD. Some non-modifiable correlates (e.g., intellectual ability, parents' ethnicity) were found to be consistently and negatively associated with PA. CONCLUSIONS: The correlates of PA in children with PD are multifaceted and along many dimensions. This review can have implications for future studies and these may confirm the consistency of variables related to PA. Insights derived from the outcomes may also foster the measurement of the magnitude of associations that could assist the development of future interventions. PMID- 27261408 TI - The association between midlife cardiorespiratory fitness and later life chronic kidney disease: The Cooper Center Longitudinal Study. AB - BACKGROUND: Chronic kidney disease (CKD) is a major public health problem, particularly in older age and in those with diabetes mellitus (DM), with high comorbidity and treatment costs. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 17,979 participants, 22% women with a mean age of 50.0 (SD 8.8), in the Cooper Center Longitudinal Study (CCLS) seen initially between 1971 to 2009 who also received Medicare coverage from 1999 to 2009. PREDICTORS: Age, body mass index, blood pressure, cholesterol, glucose levels, current tobacco use, and cardiorespiratory fitness. OUTCOMES: Incident CKD and DM were determined from Medicare administrative claims data. RESULTS: During 116,973person-years of observation, 2022 cases of incident CKD occurred. Multivariable-adjusted proportional hazards models revealed a 24% lower risk of CKD among moderate fit (hazards ratio[HR] 0.76, 95% CI 0.67-0.85 compared to low fit) and a 34% lower risk of CKD among high fit (HR 0.66, 95% CI 0.58-0.76 compared to low fit). Even following the development of DM, fitness was associated with lower risk of CKD (HR 0.94, 95% CI 0.89-0.99) per 1-MET increment. LIMITATIONS: Relatively homogeneous population of well-educated Caucasians. CONCLUSION: Results of the present study suggest that higher fitness is associated with lower risk of CKD decades later even in at-risk populations such as diabetics. The findings support a role for enhancing fitness through regular physical activity in preventive strategies for CKD including those who may develop DM in later life. PMID- 27261410 TI - Objectively measured physical activity, sedentary time and subclinical vascular disease: Cross-sectional study in older British men. AB - Low physical activity (PA) and high levels of sedentary time (ST) are associated with higher cardiovascular disease (CVD) risk among older people. However, their independent contribution and importance of duration of PA and ST bouts remain unclear. We investigated associations between objectively measured PA, ST and non invasive vascular measures, markers of CVD risk. Cross-sectional study of 1216 men from the British Regional Heart Study, mean age 78.5years, measured in 2010 2012. Carotid intima thickness (CIMT), distensibility coefficient (DC) and plaque presence were measured using ultrasound; pulse wave velocity (cfPWV) and augmentation index (AIx) using a Vicorder. PA and ST were measured using hip-worn ActiGraph GT3X accelerometers. After adjusting for covariates, each additional 1000 steps per day was associated with a 0.038m/s lower cfPWV (95% CI=-0.076, 0.0003), 0.095 10(-3) kPa(-1) higher DC (95% CI=0.006, 0.185), 0.26% lower AIx (95% CI=-0.40, -0.12) and a 0.005mm lower CIMT (95% CI=-0.008, -0.001). Moderate and vigorous PA (MVPA) was associated with lower AIx and CIMT, light PA (LPA) with lower cfPWV and CIMT and ST with higher cfPWV, AIx and CIMT and lower DC. LPA and ST were highly correlated (r=-0.62). The independence of MVPA and ST or MVPA and LPA was inconsistent across vascular measures. Bout lengths for both PA and ST were not associated with vascular measures. In our cross-sectional study of older men, all PA regardless of intensity or bout duration was beneficially associated with vascular measures, as was lower ST. LPA was particularly relevant for cfPWV and CIMT. PMID- 27261411 TI - Shared vision, shared vulnerability: A content analysis of corporate social responsibility information on tobacco industry websites. AB - Tobacco companies rely on corporate social responsibility (CSR) initiatives to improve their public image and advance their political objectives, which include thwarting or undermining tobacco control policies. For these reasons, implementation guidelines for the World Health Organization's Framework Convention on Tobacco Control (FCTC) recommend curtailing or prohibiting tobacco industry CSR. To understand how and where major tobacco companies focus their CSR resources, we explored CSR-related content on 4 US and 4 multinational tobacco company websites in February 2014. The websites described a range of CSR-related activities, many common across all companies, and no programs were unique to a particular company. The websites mentioned CSR activities in 58 countries, representing nearly every region of the world. Tobacco companies appear to have a shared vision about what constitutes CSR, due perhaps to shared vulnerabilities. Most countries that host tobacco company CSR programs are parties to the FCTC, highlighting the need for full implementation of the treaty, and for funding to monitor CSR activity, replace industry philanthropy, and enforce existing bans. PMID- 27261412 TI - Commentary: U.S. mortality, geography, and the anti-social determinants of health. AB - Drug-related overdoses appear to be a major factor behind an historic pause or even a reversal in the predominant downward trend over time in U.S. mortality rates, a departure that is especially evident among non-Hispanic white females of middle age. The new geography of accidental poisoning deaths and their covariates suggests that we should reassess traditional policies and perspectives in order to combat this threat to public health. PMID- 27261409 TI - Multilevel factors associated with long-term adherence to screening mammography in older women in the U.S. AB - In the U.S., guidelines recommend that women continue mammography screening until at least age 74, but recent evidence suggests declining screening rates in older women. We estimated adherence to screening mammography and multilevel factors associated with adherence in a longitudinal cohort of older women. Women aged 66 75years receiving screening mammography within the Breast Cancer Surveillance Consortium were linked to Medicare claims (2005-2010). Claims data identified baseline adherence, defined as receiving subsequent mammography within approximately 2years, and length of time adherent to guidelines. Characteristics associated with adherence were investigated using logistic and Cox proportional hazards regression models. Analyses were stratified by age to investigate variation in relationships between patient factors and adherence. Among 49,775 women, 89% were adherent at baseline. Among women 66-70years, those with less than a high school education were more likely to be non-adherent at baseline (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.65-2.33) and remain adherent for less time (hazard ratio [HR] 1.41; 95% CI 1.11-1.80) compared to women with a college degree. Women with >=1 versus no Charlson co-morbidities were more likely to be non-adherent at baseline (OR 1.46; 95% CI 1.31-1.62) and remain adherent for less time (HR 1.44; 95% CI 1.24-1.66). Women aged 71-75 had lower adherence overall, but factors associated with non-adherence were similar. In summary, adherence to guidelines is high among Medicare-enrolled women in the U.S. receiving screening mammography. Efforts are needed to ensure that vulnerable populations attain these same high levels of adherence. PMID- 27261413 TI - A systematic review of the parenting and outcomes experienced by offspring of mothers with borderline personality pathology: Potential mechanisms and clinical implications. AB - There is growing interest in whether the parenting strategies and offspring outcomes of mothers with borderline personality disorder (BPD) differ from those of mothers without BPD. We searched PsychINFO, PubMed, EMBASE, Web of Science, Scopus and ASSIA databases for studies examining parenting skills and attitudes among mothers with BPD/BPD symptoms and/or offspring outcomes. PRISMA reporting guidelines were followed. Of 10,067 abstracts screened, 101 full-text articles were retrieved and 33 met pre-determined criteria for qualitative synthesis. Overall, studies suggest that mothers with BPD/BPD symptoms are more likely to engage in maladaptive interactions with their offspring characterised by insensitive, overprotective, and hostile parenting compared to mothers without BPD/BPD symptoms. Adverse offspring outcomes include BPD symptoms, internalising (including depression) and externalising problems, insecure attachment patterns, and emotional dysregulation. Findings suggest that vulnerability from mother to offspring may be partly transmitted via maladaptive parenting and maternal emotional dysfunction. Conclusions were limited by study heterogeneity in methodology and construct definitions, as well as a paucity of clinical comparison groups. Prospective studies of mothers with BPD and their offspring from pregnancy onwards may further elucidate mechanisms of transmission and identify resilience factors across development. Parenting behaviour awareness, improving attachment behaviours and emotional regulation strategies may be important intervention targets. PMID- 27261414 TI - Vulnerable Hospitals and Cancer Surgery Readmissions: Insights into the Unintended Consequences of the Patient Protection and Affordable Care Act. AB - BACKGROUND: Penalties from the Hospital Readmission Reduction Program can push financially strained, vulnerable patient-serving hospitals into additional hardship. In this study, we quantified the association between vulnerable hospitals and readmissions and examined the respective contributions of patient- and hospital-related factors. METHODS: A total of 110,857 patients who underwent major cancer operations were identified from the 2004-2011 State Inpatient Database of California. Vulnerable hospitals were defined as either self identified safety net hospitals (SNHs) or hospitals with a high percentage of Medicaid patients (high Medicaid hospitals [HMHs]). We used multivariable logistic regression to determine the association between vulnerable hospitals and readmission. Patient and hospital contributions to the elevation in odds of readmission were assessed by comparing estimates from models with different subsets of predictors. RESULTS: Of the 355 hospitals, 13 were SNHs and 31 were HMHs. After adjusting for Hospital Readmission Reduction Program variables, SNHs had higher 30-day (odds ratio [OR] = 1.32; 95% CI, 1.18-1.47), 90-day (OR = 1.28; 95% CI, 1.18-1.38), and repeated readmissions (OR = 1.33; 95% CI, 1.18-1.49); HMHs also had higher 30-day (OR = 1.18; 95% CI, 1.05-1.32), 90-day (OR = 1.28; 95% CI, 1.16-1.42), and repeated readmissions (OR = 1.24; 95% CI, 1.01-1.54). Compared with patient characteristics, hospital factors accounted for a larger proportion of the increase in odds of readmission among SNHs (60% to 93% vs 24% to 39%), but a smaller proportion among HMHs (9% to 15% vs 60% to 115%). CONCLUSIONS: Vulnerable status of hospitals is associated with higher readmission rates after major cancer surgery. These findings reinforce the call to account for socioeconomic variables in risk adjustments for hospitals who serve a disproportionate share of disadvantaged patients. PMID- 27261416 TI - Treatment of rhinosinusitis and histopathology of nasal mucosa: A controlled, randomized, clinical study. AB - OBJECTIVES/HYPOTHESIS: To study the pathology of upper airway mucosa, as well as valuate and compare changes in pathology after the treatment of chronic rhinosinusitis (CRS) patients with balloon sinuplasty versus uncinectomy. METHODS: A prospective randomized controlled trial in patients with CRS of the maxillary sinuses without severe pathology of other sinuses. Patients were randomized into two groups: uncinectomy and balloon sinuplasty. The main variables in our study are histopathology of nasal mucosa and expression of metalloproteinase-9 protein. These parameters were analyzed preoperatively and at 3 months, 6 months, and 12 months postoperatively. RESULTS: Thickened epithelium, absence of cilia, metaplasia of epithelium, hyperplasia of mucosal glands, angiogenesis, and increased inflammatory cells were observed in the majority of preoperative samples. History of allergy was associated with a higher number of goblet cells, and shedding of epithelium was associated with worse quality of life. A higher number of inflammatory cells were associated with an increased number of goblet cells preoperatively, as well as after treatment. Both treatments resulted in a decrease of inflammation in the mucosa and epithelium. Hypertrophy of the mucosal glands, hyperplasia of blood vessels, and mucosal edema decreased after treatment. These changes were more noticeable in uncinectomy group. Balloon sinuplasty was associated with a higher number of inflammatory cells at 6 months after treatment (P = 0.05). LEVEL OF EVIDENCE: 1b. Laryngoscope, 126:2652-2658, 2016. PMID- 27261415 TI - A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. AB - BACKGROUND & AIMS: The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development. METHODS: A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains. RESULTS: Following initiation of the obesogenic diet, B6/129 mice developed obesity, insulin resistance, hypertriglyceridemia and increased LDL-cholesterol. They sequentially also developed steatosis (4-8weeks), steatohepatitis (16-24weeks), progressive fibrosis (16weeks onwards) and spontaneous hepatocellular cancer (HCC). There was a strong concordance between the pattern of pathway activation at a transcriptomic level between humans and mice with similar histological phenotypes (FDR 0.02 for early and 0.08 for late time points). Lipogenic, inflammatory and apoptotic signaling pathways activated in human NASH were also activated in these mice. The HCC gene signature resembled the S1 and S2 human subclasses of HCC (FDR 0.01 for both). Only the B6/129 mouse but not the parent strains recapitulated all of these aspects of human NAFLD. CONCLUSIONS: We here describe a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND) that recapitulates the key physiological, metabolic, histologic, transcriptomic and cell-signaling changes seen in humans with progressive NASH. LAY SUMMARY: We have developed a diet-induced mouse model of non-alcoholic steatohepatitis (NASH) and hepatic cancers in a cross between two mouse strains (129S1/SvImJ and C57Bl/6J). This model mimics all the physiological, metabolic, histological, transcriptomic gene signature and clinical endpoints of human NASH and can facilitate preclinical development of therapeutic targets for NASH. PMID- 27261417 TI - What symptom domains are associated with patient distress in schizophrenia? PMID- 27261418 TI - Characteristics and clinical correlates of dimensions of delusional experience in schizophrenia and delusional disorder. PMID- 27261419 TI - How much physical activity do people with schizophrenia engage in? A systematic review, comparative meta-analysis and meta-regression. AB - OBJECTIVE: Physical activity (PA) improves health outcomes in people with schizophrenia. It is unclear how much PA people with schizophrenia undertake and what influences PA participation. We conducted a meta-analysis to investigate PA levels and predictors in people with schizophrenia. METHOD: Major databases were searched from inception till 02/2016 for articles measuring PA (self-report questionnaire (SRQ) or objective measure (e.g. accelerometer)) in people with schizophrenia, including first episode psychosis (FEP). A random effects meta analysis and meta-regression analysis were conducted. RESULTS: 35 studies representing 3453 individuals with schizophrenia (40.0years; 64.0% male) were included. Engagement in light PA was 80.44min (95% CI 68.32-92.52, n=2658), 47.1min moderate-vigorous PA (95% CI 31.5-62.8, n=559) and 1.05min (95% CI 0.48 1.62, n=2533) vigorous PA per day. People with schizophrenia engaged in significantly less moderate (hedges g=-0.45, 95% CI -0.79 to -0.1, p=0.01) and vigorous PA (g=-0.4, 95% CI -0.60 to -0.18) versus controls. Higher light to moderate, but lower vigorous PA levels were observed in outpatients and in studies utilizing objective measures versus SRQ. 56.6% (95% CI 45.8-66.8, studies=12) met the recommended 150min of moderate physical activity per week. Depressive symptoms and older age were associated with less vigorous PA in meta regression analyses. CONCLUSIONS: Our data confirm that people with schizophrenia engage in significantly less moderate and vigorous PA versus controls. Interventions aiming to increase PA, regardless of intensity are indicated for people with schizophrenia, while specifically increasing moderate-vigorous PA should be a priority given the established health benefits. PMID- 27261420 TI - Geographical variation in the management of urolithiasis in Australia. AB - BACKGROUND: To examine any geographical variation in the management of urolithiasis amongst the Australian states and territories. METHODS: Retrospective study with data obtained from the Medicare Australia database, the Royal Australasian College of Surgeons and the Urological Society of Australia and New Zealand. RESULTS: Minimally invasive stone treatment with shock wave lithotripsy (SWL) and ureteroscopy (URS) accounted for the majority of stone treatments in Australia (98%). Variation of stone treatment modalities exists amongst the Australian states and territories with an inverse relationship between the use of SWL and URS. We compared Western Australia (WA) and Queensland (QLD) which have a comparable geographical area. SWL accounts for 1% and 22% of stone treatments in WA and QLD, respectively. In WA, urologists are concentrated in two cities with no SWL available in the private sector. In QLD, urologists are distributed in 11 cities with SWL available in both the public and private sector. The three largest states or territories by geographical area - the Northern Territory, WA and QLD - have stone treatment rates of 1:1337, 1:1110 and 1:2432 per capita of privately insured patients, respectively. In comparison, smaller Australian states/territories such as Tasmania and Victoria have stone treatment rates of 1:619 and 1:765 per capita of privately insured patients, respectively. CONCLUSION: The distribution of urologists and treatment modalities available in each state or territory appear to play a contributory role in choice of treatment modality. In addition, inequality to stone treatment access exists in geographically large Australian states/territories. PMID- 27261421 TI - Maps of heavy metals in the soils of the European Union and proposed priority areas for detailed assessment. AB - Soil contamination is one of the greatest concerns among the threats to soil resources in Europe and globally. Despite of its importance there was only very course scale (1/5000km(2)) data available on soil heavy metal concentrations prior to the LUCAS topsoil survey, which had a sampling density of 200km(2). Based on the results of the LUCAS sampling and auxiliary information detailed and up-to-date maps of heavy metals (As, Cd, Cr, Cu, Hg, Pb, Zn, Sb, Co and Ni) in the topsoil of the European Union were produced. Using the maps of heavy metal concentration in topsoil we made a spatial prediction of areas where local assessment is suggested to monitor and eventually control the potential threat from heavy metals. Most of the examined elements remain under the corresponding threshold values in the majority of the land of the EU. However, one or more of the elements exceed the applied threshold concentration on 1.2Mkm(2), which is 28.3% of the total surface area of the EU. While natural backgrounds might be the reason for high concentrations on large proportion of the affected soils, historical and recent industrial and mining areas show elevated concentrations (predominantly of As, Cd, Pb and Hg) too, indicating the magnitude of anthropogenic effect on soil quality in Europe. PMID- 27261422 TI - One-year study of polycyclic aromatic compounds at an urban site in Grenoble (France): Seasonal variations, gas/particle partitioning and cancer risk estimation. AB - 21 PAHs, 27 oxy-PAHs and 32 nitro-PAHs were measured every third day over a year in both gaseous (G) and particulate PM10 (P) phases in ambient air of Grenoble (France). Mean total concentrations (G+P) of PAHs and oxy-PAHs were in the same range and about 10ngm(-3). Nitro-PAHs were 50 to 100 times less concentrated averaging 100pgm(-3). Polycyclic aromatic compound (PAC) concentrations were 5 to 7 times higher in "cold" period (October to March) than in "warm" period (April to September). Seasonal variations may be explained by higher primary emissions from residential heating, especially biomass burning in "cold" season. Meteorological conditions and influence of the geomorphology around Grenoble, with the formation of thermal inversion layers leading to the stagnation of pollutants, were additional key parameters. Maximum individual PAC concentrations were observed during two PM10 pollution events in December and February-March. Chemical processes and secondary formation of oxy- and nitro-PAH were probably enhanced by the accumulation of the pollutants during these events. PAC gas/particle partitioning depended on compound molecular weight and vapour pressure. Gas/particle partitioning of oxy- and nitro-PAHs were evaluated using a multi-phase poly-parameter linear free energy relationship model. The PAC cancer risk was assessed using toxic equivalency factors available in the literature (19 PAHs, 10 nitro-PAHs and 1 oxy-PAH). Overall, particle-bound PACs contributed about 76% of the cancer risk. While PAHs accounted for most of the total PAC cancer risk, oxy- and nitro-PAHs could account for up to 24%. The risk quantification across substance classes is limited by toxicological data availability. PMID- 27261423 TI - Changes in the CO2 dynamics in near-surface cavities under a future warming scenario: Factors and evidence from the field and experimental findings. PMID- 27261424 TI - Observation of aerosol size distribution and new particle formation at a coastal city in the Yangtze River Delta, China. AB - Aerosol number size distribution in the range of 10nm-10MUm, trace gases (O3, CO, SO2 and NO2), particular matter (PM: PM2.5 and PM10) and meteorological elements were measured from the 1st to the 31st of May, 2015, in the coastal city of Jiaxing in the Yangtze River Delta (YRD). The average number concentration and surface area concentration were 19,639cm(-3) and 427MUm(2)cm(-3) during the observation period. The different mode particle concentrations ranked in the order of Aitken mode (12,361cm(-3))>nucleation (4926.7cm(-3))>accumulation (2349.3cm(-3))>coarse mode (1.7cm(-3)). The average concentrations of CO, SO2, NO2, O3, PM2.5 and PM10 were 0.545mgm(-3), 14.7, 35.1, 89.8, 43.5 and 64.6MUgm( 3), respectively. Eight precipitation processes and 15 new particle formation (NPF) events (3 NPF events occurred on a rainy day) were observed. Results show that the precipitation process had greater scavenging effects on particles smaller than 120nm and larger than 2MUm. The spectral distributions of number concentrations were unimodal at different weather conditions, with peaks at 20nm, 40-60nm, 50-80nm on NPF days, rainy days and normal days. During the NPF events, the formation rate (FR), growth rate (GR), condensational sink (CS), vapor source rate (Q) and condensing vapor concentration (C) were in the range of 4.0-17.0cm( 3)s(-1), 2.2-15.7nmh(-1), 1.5-5.8*10(-2)s(-1), 0.5-7.7*10(6)cm(-3)s(-1) and 3.0 21.5*10(7)cm(-3), with mean values of 9.6cm(-3)s(-1), 6.8nmh(-1), 3.4*10(-2)s( 1), 3.3*10(6)cm(-3)s(-1) and 9.4*10(7)cm(-3), respectively. NPF events normally occurred under clean atmospheric conditions with low PM concentrations but high levels of trace gases. It was also found that SO2 plays an important role in NPF and growth in Jiaxing. PMID- 27261425 TI - Watershed-scale impacts of stormwater green infrastructure on hydrology, nutrient fluxes, and combined sewer overflows in the mid-Atlantic region. AB - Stormwater green infrastructure (SGI), including rain gardens, detention ponds, bioswales, and green roofs, is being implemented in cities across the globe to reduce flooding, combined sewer overflows, and pollutant transport to streams and rivers. Despite the increasing use of urban SGI, few studies have quantified the cumulative effects of multiple SGI projects on hydrology and water quality at the watershed scale. To assess the effects of SGI, Washington, DC, Montgomery County, MD, and Baltimore County, MD, were selected based on the availability of data on SGI, water quality, and stream flow. The cumulative impact of SGI was evaluated over space and time by comparing watersheds with and without SGI, and by assessing how long-term changes in SGI impact hydrologic and water quality metrics over time. Most Mid-Atlantic municipalities have a goal of achieving 10 20% of the landscape drain runoff through SGI by 2030. Of these areas, Washington, DC currently has the greatest amount of SGI (12.7% of the landscape drained through SGI), while Baltimore County has the lowest (7.9%). When controlling for watersheds size and percent impervious surface cover, watersheds with greater amounts of SGI have less flashy hydrology, with 44% lower peak runoff, 26% less frequent runoff events, and 26% less variable runoff. Watersheds with more SGI also show 44% less NO3(-) and 48% less total nitrogen exports compared to watersheds with minimal SGI. There was no significant reduction in phosphorus exports or combined sewer overflows in watersheds with greater SGI. When comparing individual watersheds over time, increases in SGI corresponded to non-significant reductions in hydrologic flashiness compared to watersheds with no change in SGI. While the implementation of SGI is somewhat in its infancy in some regions, cities are beginning to have a scale of SGI where there are statistically significant differences in hydrologic patterns and water quality. PMID- 27261427 TI - The magnitude and relevance of the February 2014 radiation release from the Waste Isolation Pilot Plant repository in New Mexico, USA. AB - After almost fifteen years of successful waste disposal operations, the first unambiguous airborne radiation release from the Waste Isolation Pilot Plant (WIPP) was detected beyond the site boundary on February 14, 2014. It was the first accident of its kind in the 15-year operating history of the WIPP. The accident released moderate levels of radioactivity into the underground air. A small but measurable amount of radioactivity also escaped to the surface through the ventilation system and was detected above ground. The dominant radionuclides released were americium and plutonium, in a ratio consistent with the known content of a breached drum. The radiation release was caused by a runaway chemical reaction inside a transuranic (TRU) waste drum which experienced a seal and lid failure, spewing radioactive materials into the repository. According to source-term estimation, approximately 2 to 10Ci of radioactivity was released from the breached drum into the underground, and an undetermined fraction of that source term became airborne, setting off an alarm and triggering the closure of seals designed to force exhausting air through a system of filters including high efficiency-particulate-air (HEPA) filters. Air monitoring across the WIPP site intensified following the first reports of radiation detection underground to determine the extent of impact to WIPP personnel, the public, and the environment, if any. This article attempts to compile and interpret analytical data collected by an independent monitoring program conducted by the Carlsbad Environmental Monitoring & Research Center (CEMRC) and by a compliance-monitoring program conducted by the WIPP's management and operating contractor, the Nuclear Waste Partnership (NWP), LLC., in response to the accident. Both the independent and the WIPP monitoring efforts concluded that the levels detected were very low and localized, and no radiation-related health effects among local workers or the public would be expected. PMID- 27261426 TI - Double pulse laser induced breakdown spectroscopy: A potential tool for the analysis of contaminants and macro/micronutrients in organic mineral fertilizers. AB - Organic fertilizers are obtained from waste of plant or animal origin. One of the advantages of organic fertilizers is that, from the composting, it recycles waste organic of urban and agriculture origin, whose disposal would cause environmental impacts. Fast and accurate analysis of both major and minor/trace elements contained in organic mineral and inorganic fertilizers of new generation have promoted the application of modern analytical techniques. In particular, laser induced breakdown spectroscopy (LIBS) is showing to be a very promising, quick and practical technique to detect and measure contaminants and nutrients in fertilizers. Although, this technique presents some limitations, such as a low sensitivity, if compared to other spectroscopic techniques, the use of double pulse (DP) LIBS is an alternative to the conventional LIBS in single pulse (SP). The macronutrients (Ca, Mg, K, P), micronutrients (Cu, Fe, Na, Mn, Zn) and contaminant (Cr) in fertilizer using LIBS in SP and DP configurations were evaluated. A comparative study for both configurations was performed using optimized key parameters for improving LIBS performance. The limit of detection (LOD) values obtained by DP LIBS increased up to seven times as compared to SP LIBS. In general, the marked improvement obtained when using DP system in the simultaneous LIBS quantitative determination for fertilizers analysis could be ascribed to the larger ablated mass of the sample. The results presented in this study show the promising potential of the DP LIBS technique for a qualitative analysis in fertilizers, without requiring sample preparation with chemical reagents. PMID- 27261428 TI - Geochemical record of high emperor penguin populations during the Little Ice Age at Amanda Bay, Antarctica. AB - Emperor penguins (Aptenodytes forsteri) are sensitive to the Antarctic climate change because they breed on the fast sea ice. Studies of paleohistory for the emperor penguin are rare, due to the lack of archives on land. In this study, we obtained an emperor penguin ornithogenic sediment profile (PI) and performed geochronological, geochemical and stable isotope analyses on the sediments and feather remains. Two radiocarbon dates of penguin feathers in PI indicate that emperor penguins colonized Amanda Bay as early as CE 1540. By using the bio elements (P, Se, Hg, Zn and Cd) in sediments and stable isotope values (delta(15)N and delta(13)C) in feathers, we inferred relative population size and dietary change of emperor penguins during the period of CE 1540-2008, respectively. An increase in population size with depleted N isotope ratios for emperor penguins on N island at Amanda Bay during the Little Ice Age (CE 1540 1866) was observed, suggesting that cold climate affected the penguin's breeding habitat, prey availability and thus their population and dietary composition. PMID- 27261429 TI - Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health. AB - Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23 and 41weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6ng/ml, neonatal TSH and FT4 was 2.20 MUU/ml and 2.03ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary. PMID- 27261430 TI - Occurrence of methicillin-resistant Staphylococcus aureus in surface waters near industrial hog operation spray fields. AB - Industrial hog operations (IHOs) have been identified as a source of antibiotic resistant Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). However, few studies have investigated the presence of antibiotic resistant S. aureus in the environment near IHOs, specifically surface waters proximal to spray fields where IHO liquid lagoon waste is sprayed. Surface water samples (n=179) were collected over the course of approximately one year from nine locations in southeastern North Carolina and analyzed for the presence of presumptive MRSA using CHROMagar MRSA media. Culture-based, biochemical, and molecular tests, as well as matrix-assisted laser desorption/ionization-time of flight mass spectrometry were used to confirm that isolates that grew on CHROMagar MRSA media were S. aureus. Confirmed S. aureus isolates were then tested for susceptibility to 16 antibiotics and screened for molecular markers of MRSA (mecA, mecC) and livestock adaptation (absence of scn). A total of 12 confirmed MRSA were detected in 9 distinct water samples. Nine of 12 MRSA isolates were also multidrug-resistant (MDRSA [i.e., resistant to >=3 antibiotic classes]). All MRSA were scn-positive and most (11/12) belonged to a staphylococcal protein A (spa) type t008, which is commonly associated with humans. Additionally, 12 confirmed S. aureus that were methicillin-susceptible (MSSA) were recovered, 7 of which belonged to spa type t021 and were scn-negative (a marker of livestock-adaptation). This study demonstrated the presence of MSSA, MRSA, and MDRSA in surface waters adjacent to IHO lagoon waste spray fields in southeastern North Carolina. To our knowledge, this is the first report of waterborne S. aureus from surface waters proximal to IHOs. PMID- 27261431 TI - A Systematic Review on the Acceptability and Tolerability of Transcranial Direct Current Stimulation Treatment in Neuropsychiatry Trials. AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation investigated as a treatment for several neuropsychiatric disorders. Notwithstanding tDCS-induced adverse events (AEs) are considered to be low and transient, systematic review analyses on safety and tolerability of tDCS derive mostly from single-session studies. OBJECTIVE: To investigate the tolerability (rate of AEs) and acceptability (rate of dropouts) of tDCS. METHODS: Systematic review and meta-analysis of tDCS randomized, sham-controlled trials in healthy or neuropsychiatric adult samples from the first date available to March 9, 2016. We only included parallel studies performing at least 5 tDCS sessions. An adapted version of CONSORT guidelines for reporting harms outcomes was used to evaluate AE reporting. RESULTS: Sixty-four studies (2262 participants) were included. They had a low risk of publication bias and methodological bias for the items assessed. Dropout rates in active and sham tDCS groups were, respectively, 6% and 7.2% (OR = 0.82 [0.59-1.14]). However, almost half of studies reported no dropouts and only 23.4% reported its reasons; when reported, the most frequent reasons were AEs and protocol violation. A tolerability meta-analysis was not performed, as most studies did not report AEs. The quality of AEs reporting was also limited, particularly in smaller studies and stroke studies. CONCLUSIONS: Although overall dropout rate was low and similar in active and sham groups, studies did not adequately describe AEs. An updated questionnaire and guidelines for assessment of AEs in tDCS trials are proposed in order to standardize the reporting of AE in the field. PMID- 27261432 TI - Identification of poly(rC) binding protein 2 (PCBP2) as a target protein of immunosuppressive agent 15-deoxyspergualin. AB - 15-Deoxyspergualin (DSG) is an immunosuppressive agent being clinically used. Unlike tacrolimus and cyclosporine A, it does not inhibit the calcineurin pathway, and its mechanism of action and target molecule have not been elucidated. Therefore, we previously prepared biotinylated derivative of DSG (BDSG) to fish up the target protein. In the present research, we identified poly(rC) binding protein 2 (PCBP2) as a DSG-binding protein using this probe. DSG was confirmed to bind to PCBP2 by pull-down assay. Intracellular localization of PCBP2 was changed from the nucleus to the cytoplasm by DSG treatment. DSG inhibited the cell growth, and over-expression of PCBP2 reduced the anti proliferative activity of DSG. PCBP2 is known to regulate various proteins including STAT1/2. Thus, we found PCBP2 as the first target protein of DSG that can explain the immunosuppressive activity. PMID- 27261433 TI - Retention of gene expression in porcine islets after agarose encapsulation and long-term culture. AB - Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expression profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. PMID- 27261434 TI - Transcriptional regulation of bone sialoprotein gene expression by Osx. AB - Osteoporosis is the most common metabolic bone disease characterized by decreased bone mass, decreased bone strength, and increased risk of fracture. It is due to unbalance between bone formation and bone resorption. Bone formation is a complex process which involves the differentiation of mesenchymal stem cells to osteoblasts. Osteoblasts produce a characteristic extracellular collagenous matrix that subsequently becomes mineralized. Osterix (Osx) is an osteoblast specific transcription factor required for osteoblast differentiation. Bone sialoprotein (Bsp) is a member of the SIBLING gene family. Expression of Bsp correlates with the differentiation of osteoblasts and the onset of mineralization. Our preliminary data showed that Bsp was abolished in Osx-null mice; however, the detailed mechanism of Osx regulation on Bsp is not fully understood. In this study, regulation of Bsp expression by Osx was further characterized. It was shown that overexpression of Osx led to Bsp upregulation. Inhibition of Osx by small interfering RNA resulted in Bsp downregulation in osteoblast. Transfection assay demonstrated that Osx was able to activate Bsp promoter reporter in a dose-dependent manner. To define minimal region of Bsp promoter activated by Osx, a series of deletion mutants of Bsp promoter were generated, and the minimal region was narrowed down to the proximal 100 bp. Point mutagenesis studies showed that one GC-rich site was required for Bsp promoter activation by Osx. ChIP assays demonstrated that endogenous Osx associated with native Bsp promoter in primary osteoblasts. Our observations provide evidence that Osx targets Bsp expression directly. PMID- 27261445 TI - Towards an Inclusive Occupational Health and Safety For Informal Workers. AB - Large numbers of workers worldwide work informally. Yet the discipline and practice of occupational health and safety covers largely only formal workers, in formal work places. A comprehensive approach would have to take into account specific hazards faced by those in different occupations, working in "atypical" work places. Local authorities exert significant influence in the provision of infrastructure that impacts on health and safety, such as water and sanitation. Examples from Brazil and Ghana show that positive interventions are possible so long as informal workers are recognized as contributing to the economy. A more inclusive occupational health and safety is most likely to happen in contexts where informal workers have an organized voice and where there are responsive health and safety personnel who understand that the world of work has changed. Some policy interventions that impact on healthy and safe work will need to involve multiple stakeholders and institutions. PMID- 27261446 TI - The Effect of Smoking on Corneal Biomechanics. AB - PURPOSE: To determine the effect of smoking on corneal biomechanical behavior. MATERIALS AND METHODS: The medical records of consecutive patients that presented to the ophthalmology department were reviewed. History of smoking and ophthalmological examination findings were recorded. The smoking group met the following criteria: a clear history of and present smoking habit, negative history of corneal disease and surgery, ocular response analyzer measurement at the time of examination, and a waveform score >=3.7. Nonsmokers (never smoked or quit smoking >=6 months earlier) that met the same criteria constituted the control group. Corneal biomechanical parameters were measured using ocular response analyzer. Data were analyzed using Pearson's chi2 test, Mann-Whitney U test, and Spearman's correlation coefficient. RESULTS: The smoking group included 166 eyes of 166 patients with a mean age of 38.7 +/- 11.95 years, and the control group consisted of 170 eyes of 170 patients with a mean age of 38.40 +/- 12.2 years. Mean cumulative smoking dose in the smoking group was 9.59 +/- 11.87 pack years (0.04- 75.00). There was no significant correlation between cumulative smoking dose and corneal hysteresis and corneal resistance factor (P = 0.382 and 0.074, respectively). There were no significant differences in corneal hysteresis or the corneal resistance factor between the two groups (P > 0.05). There was no significant difference in corneal hysteresis between those in the smoking group aged 18-44 years and those aged 45-64 years (P = 0.258), whereas in the control group mean corneal hysteresis was significantly lower in the 45-64 year olds than in the 18-44 year olds (P = 0.034). CONCLUSIONS: Although there was no significant difference in corneal biomechanics between smoking and control groups, the decrease in corneal hysteresis with aging was less apparent in the smoking group, which may be due to the potential changes in the cornea's microstructure induced by smoking during aging and the effect of smoking in aged corneal tissue viscosity. PMID- 27261447 TI - Letter Regarding: The Internet for Patient Education: A Friend or Foe? PMID- 27261448 TI - Response to "Letter Regarding: The Internet for Patient Education: A Friend or Foe?". PMID- 27261451 TI - Personalized medicine in cystic fibrosis: genistein supplementation as a treatment option for patients with a rare S1045Y-CFTR mutation. AB - Cystic fibrosis (CF) is a life-shortening disease caused by the mutations that generate nonfunctional CF transmembrane conductance regulator (CFTR) protein. A rare serine-to-tyrosine (S1045Y) CFTR mutation was earlier reported to result in CF-associated fatality. We identified an African-American patient with the S1045Y mutation in CFTR, as well as a stop-codon mutation, who has a mild CF phenotype. The underlying mechanism of CF caused by S1045Y-CFTR has not been elucidated. In this study, we determined that S1045Y-CFTR exhibits twofold attenuated function compared with wild-type (WT)-CFTR. We report that serine-to-tyrosine mutation leads to increased tyrosine phosphorylation of S1045Y-CFTR, followed by recruitment and binding of E3-ubiquitin ligase c-cbl, resulting in enhanced ubiquitination and passage of S1045Y-CFTR in the endosome/lysosome degradative compartments. We demonstrate that inhibition of tyrosine phosphorylation partially rescues S1045Y-CFTR surface expression and function. Based on our findings, it could be suggested that consuming genistein (a tyrosine phosphorylation inhibitor) would likely ameliorate CF symptoms in individuals with S1045Y-CFTR, providing a unique personalized therapy for this rare CF mutation. PMID- 27261450 TI - The quantity and quality of alpha-gal-specific antibodies differ in individuals with and without delayed red meat allergy. AB - BACKGROUND: IgG to galactose-alpha-1,3-galactose (alpha-gal) are highly abundant natural antibodies (Ab) in humans. alpha-Gal-specific IgE Ab cause a special form of meat allergy characterized by severe systemic reactions 3-7 h after consumption of red meat. We investigated 20 patients who experienced such reactions and characterized their alpha-gal-specific IgE and IgG responses in more detail. METHODS: alpha-Gal-specific IgE was determined by ImmunoCAP. IgE reactivity to meat extract and bovine gamma globulin (BGG) was assessed by immunoblotting and ELISA, respectively. In some experiments, sera were pre incubated with alpha-gal or protein G to deplete IgG Ab. alpha-Gal-specific IgG1 4 Ab in individuals with and without meat allergy were assessed by ELISA. RESULTS: In immunoblots, BGG was the most frequently recognized meat protein. Binding of IgE and IgG to BGG was confirmed by ELISA and completely abolished after pre-incubation with alpha-gal. Neither the depletion of autologous alpha gal-specific IgG Ab nor the addition of alpha-gal-specific IgG Ab from nonallergic individuals changed the IgE recognition of BGG of meat-allergic patients. Meat-allergic patients showed significantly higher alpha-gal-specific IgG1 and IgG3 Ab than nonallergic individuals, whereas the latter showed significantly higher levels of alpha-gal-specific IgG4 Ab. CONCLUSION: Patients with delayed meat allergy display IgE and IgG Ab that selectively recognize the alpha-gal epitope on BGG. Their enhanced alpha-gal-specific IgE levels are accompanied by high levels of alpha-gal-specific IgG1 devoid of IgE-blocking activity. This subclass distribution is atypical for food allergies and distinct from natural alpha-gal IgG responses in nonallergic individuals. PMID- 27261453 TI - Shaping risky choices: Ethics and the effects of organizational decisions. AB - Choices to live "at risk" are complex and challenging and can be structured by organizational policy. Some individuals genuinely wish to live in situations that are, or are perceived to be, high risk because this affords them an important benefit. However, it is likely that these choices are significantly affected by context and might not be made under different circumstances. The following argues for a responsibility to be attentive to the effects of organizational decisions on choices to live at risk and the overall distribution of risk. PMID- 27261452 TI - Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis. AB - Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) components that results in destruction of the normal pleural tissue architecture. It can result from diverse inflammatory conditions, especially tuberculous pleurisy. Pleural mesothelial cells (PMCs) play a pivotal role in pleural fibrosis. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in pleural fibrosis remains unknown. In the present study, we found that tuberculous pleural effusion (TPE) induced calpain activation in PMCs and that inhibition of calpain prevented TPE-induced collagen-I synthesis and cell proliferation of PMCs. Moreover, our data revealed that the levels of angiotensin (ANG)-converting enzyme (ACE) were significantly higher in pleural fluid of patients with TPE than those with malignant pleural effusion, and ACE-ANG II in TPE resulted in activation of calpain and subsequent triggering of the phosphatidylinositol 3 kinase (PI3K)/Akt/NF-kappaB signaling pathway in PMCs. Finally, calpain activation in PMCs and collagen depositions were confirmed in pleural biopsy specimens from patients with tuberculous pleurisy. Together, these studies demonstrated that calpain is activated by renin-angiotensin system in pleural fibrosis and mediates TPE-induced collagen-I synthesis and proliferation of PMCs via the PI3K/Akt/NF-kappaB signaling pathway. Calpain in PMCs might be a novel target for intervention in tuberculous pleural fibrosis. PMID- 27261454 TI - The influence of anthropometrics on physical employment standard performance. AB - BACKGROUND: The Canadian Armed Forces (CAF) recently implemented the Fitness for Operational Requirements of CAF Employment (FORCE), a new physical employment standard (PES). Data collection throughout development included anthropometric profiles of the CAF. AIMS: To determine if anthropometric measurements and demographic information would predict the performance outcomes of the FORCE and/or Common Military Task Fitness Evaluation (CMTFE). METHODS: We conducted a secondary analysis of data from FORCE research. We obtained bioelectrical impedance and segmental analysis. Statistical analysis included correlation and linear regression analyses. RESULTS: Among the 668 study subjects, as predicted, any task requiring lifting, pulling or moving of an object was significantly and positively correlated (r > 0.67) to lean body mass (LBM) measurements. LBM correlated with stretcher carry (r = 0.78) and with lifting actions such as sand bag drag (r = 0.77), vehicle extrication (r = 0.71), sand bag fortification (r = 0.68) and sand bag lift time (r = -0.67). The difference between the correlation of dead mass (DM) with task performance compared with LBM was not statistically significant. CONCLUSIONS: DM and LBM can be used in a PES to predict success on military tasks such as casualty evacuation and manual material handling. However, there is no minimum LBM required to perform these tasks successfully. These data direct future research on how we should diversify research participants by anthropometrics, in addition to the traditional demographic variables of gender and age, to highlight potential important adverse impact with PES design. In addition, the results can be used to develop better training regimens to facilitate passing a PES. PMID- 27261455 TI - Comprehensive and Holistic Analysis of HT-29 Colorectal Cancer Cells and Tumor Bearing Nude Mouse Model: Interactions Among Fractions Derived From the Chinese Medicine Formula Tian Xian Liquid in Effects on Human Colorectal Carcinoma. AB - The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 mRNA; TXL potently reversed most multidrug resistance via downregulation of MDR-1 protein. In conclusion, the comprehensive and holistic effects of TXL were demonstrated with ( a) mutual accentuation and mutual enhancement, ( b) mutual counteraction and mutual suppression, and ( c) mutual antagonism among the 3 constituent fractions. Moreover, the design of the present study may lead to further development of more tissue-specific effective drugs with minimal side effects for clinical use in combating carcinoma. PMID- 27261456 TI - ANTICALIgN: visualizing, editing and analyzing combined nucleotide and amino acid sequence alignments for combinatorial protein engineering. AB - ANTIC ALIGN: is an interactive software developed to simultaneously visualize, analyze and modify alignments of DNA and/or protein sequences that arise during combinatorial protein engineering, design and selection. ANTIC ALIGN: combines powerful functions known from currently available sequence analysis tools with unique features for protein engineering, in particular the possibility to display and manipulate nucleotide sequences and their translated amino acid sequences at the same time. ANTIC ALIGN: offers both template-based multiple sequence alignment (MSA), using the unmutated protein as reference, and conventional global alignment, to compare sequences that share an evolutionary relationship. The application of similarity-based clustering algorithms facilitates the identification of duplicates or of conserved sequence features among a set of selected clones. Imported nucleotide sequences from DNA sequence analysis are automatically translated into the corresponding amino acid sequences and displayed, offering numerous options for selecting reading frames, highlighting of sequence features and graphical layout of the MSA. The MSA complexity can be reduced by hiding the conserved nucleotide and/or amino acid residues, thus putting emphasis on the relevant mutated positions. ANTIC ALIGN: is also able to handle suppressed stop codons or even to incorporate non-natural amino acids into a coding sequence. We demonstrate crucial functions of ANTIC ALIGN: in an example of Anticalins selected from a lipocalin random library against the fibronectin extradomain B (ED-B), an established marker of tumor vasculature. Apart from engineered protein scaffolds, ANTIC ALIGN: provides a powerful tool in the area of antibody engineering and for directed enzyme evolution. PMID- 27261457 TI - Tumor Progression Locus 2 (Tpl2) Activates the Mammalian Target of Rapamycin (mTOR) Pathway, Inhibits Forkhead Box P3 (FoxP3) Expression, and Limits Regulatory T Cell (Treg) Immunosuppressive Functions. AB - The serine/threonine kinase tumor progression locus 2 (Tpl2, also known as Map3k8/Cot) is a potent inflammatory mediator that drives the production of TNFalpha, IL-1beta, and IFNgamma. We previously demonstrated that Tpl2 regulates T cell receptor (TCR) signaling and modulates T helper cell differentiation. However, very little is known about how Tpl2 modulates the development of regulatory T cells (Tregs). Tregs are a specialized subset of T cells that express FoxP3 and possess immunosuppressive properties to limit excess inflammation. Because of the documented role of Tpl2 in promoting inflammation, we hypothesized that Tpl2 antagonizes Treg development and immunosuppressive function. Here we demonstrate that Tpl2 constrains the development of inducible Tregs. Tpl2(-/-) naive CD4(+) T cells preferentially develop into FoxP3(+) inducible Tregs in vitro as well as in vivo in a murine model of ovalbumin (OVA) induced systemic tolerance. Treg biasing of Tpl2(-/-) T cells depended on TCR signal strength and corresponded with reduced activation of the mammalian target of rapamycin (mTOR) pathway. Importantly, Tpl2(-/-) Tregs have basally increased expression of FoxP3 and immunosuppressive molecules, IL-10 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Furthermore, they were more immunosuppressive in vivo in a T cell transfer model of colitis, as evidenced by reduced effector T cell accumulation, systemic production of inflammatory cytokines, and colonic inflammation. These results demonstrate that Tpl2 promotes inflammation in part by constraining FoxP3 expression and Treg immunosuppressive functions. Overall, these findings suggest that Tpl2 inhibition could be used to preferentially drive Treg induction and thereby limit inflammation in a variety of autoimmune diseases. PMID- 27261458 TI - Nitrogen Starvation-induced Phosphorylation of Ras1 Protein and Its Potential Role in Nutrient Signaling and Stress Response. AB - Ras1 is a small GTPase in the budding yeast Saccharomyces cerevisiae that regulates nutrient signaling. It has been shown that Ras1 undergoes phosphorylation, but the functional consequences and regulation of Ras1 phosphorylation remain unknown. Here we identify Ser-226 as an important residue for Ras1 phosphorylation, as mutating this residue to an alanine drastically diminishes the level of Ras1 phosphorylation. Notably, phosphorylated Ras1 accumulates as the cells approach the stationary phase of growth. Likewise, subjecting cells to nitrogen starvation also elevates the level of Ras1 phosphorylation. Interestingly, blocking Ras1 phosphorylation diminishes the level of autophagy and also renders the cells more sensitive to heat shock. Together, these data suggest a role of Ras1 phosphorylation in modulating nutrient signaling and stress response. PMID- 27261459 TI - miR-30 Family Controls Proliferation and Differentiation of Intestinal Epithelial Cell Models by Directing a Broad Gene Expression Program That Includes SOX9 and the Ubiquitin Ligase Pathway. AB - Proliferation and differentiation of intestinal epithelial cells (IECs) occur in part through precise regulation of key transcription factors, such as SOX9. MicroRNAs (miRNAs) have emerged as prominent fine-tuners of transcription factor expression and activity. We hypothesized that miRNAs, in part through the regulation of SOX9, may mediate IEC homeostasis. Bioinformatic analyses of the SOX9 3'-UTR revealed highly conserved target sites for nine different miRNAs. Of these, only the miR-30 family members were both robustly and variably expressed across functionally distinct cell types of the murine jejunal epithelium. Inhibition of miR-30 using complementary locked nucleic acids (LNA30bcd) in both human IECs and human colorectal adenocarcinoma-derived Caco-2 cells resulted in significant up-regulation of SOX9 mRNA but, interestingly, significant down regulation of SOX9 protein. To gain mechanistic insight into this non-intuitive finding, we performed RNA sequencing on LNA30bcd-treated human IECs and found 2440 significantly increased genes and 2651 significantly decreased genes across three time points. The up-regulated genes are highly enriched for both predicted miR-30 targets, as well as genes in the ubiquitin-proteasome pathway. Chemical suppression of the proteasome rescued the effect of LNA30bcd on SOX9 protein levels, indicating that the regulation of SOX9 protein by miR-30 is largely indirect through the proteasome pathway. Inhibition of the miR-30 family led to significantly reduced IEC proliferation and a dramatic increase in markers of enterocyte differentiation. This in-depth analysis of a complex miRNA regulatory program in intestinal epithelial cell models provides novel evidence that the miR 30 family likely plays an important role in IEC homeostasis. PMID- 27261460 TI - Regulation of the Yeast Hxt6 Hexose Transporter by the Rod1 alpha-Arrestin, the Snf1 Protein Kinase, and the Bmh2 14-3-3 Protein. AB - Cell viability requires adaptation to changing environmental conditions. Ubiquitin-mediated endocytosis plays a crucial role in this process, because it provides a mechanism to remove transport proteins from the membrane. Arrestin related trafficking proteins are important regulators of the endocytic pathway in yeast, facilitating selective ubiquitylation of target proteins by the E3 ubiquitin ligase, Rsp5. Specifically, Rod1 (Art4) has been reported to regulate the endocytosis of both the Hxt1, Hxt3, and Hxt6 glucose transporters and the Jen1 lactate transporter. Also, the AMP kinase homologue, Snf1, and 14-3-3 proteins have been shown to regulate Jen1 via Rod1. Here, we further characterized the role of Rod1, Snf1, and 14-3-3 in the signal transduction route involved in the endocytic regulation of the Hxt6 high affinity glucose transporter by showing that Snf1 interacts specifically with Rod1 and Rog3 (Art7), that the interaction between the Bmh2 and several arrestin-related trafficking proteins may be modulated by carbon source, and that both the 14-3-3 protein Bmh2 and the Snf1 regulatory domain interact with the arrestin-like domain containing the N-terminal half of Rod1 (amino acids 1-395). Finally, using both co-immunoprecipitation and bimolecular fluorescence complementation, we demonstrated the interaction of Rod1 with Hxt6 and showed that the localization of the Rod1-Hxt6 complex at the plasma membrane is affected by carbon source and is reduced upon overexpression of SNF1 and BMH2. PMID- 27261461 TI - Cellular Redox Systems Impact the Aggregation of Cu,Zn Superoxide Dismutase Linked to Familial Amyotrophic Lateral Sclerosis. AB - Protein misfolding is implicated in neurodegenerative diseases such as ALS, where mutations of superoxide dismutase 1 (SOD1) account for about 20% of the inherited mutations. Human SOD1 (hSOD1) contains four cysteines, including Cys(57) and Cys(146), which have been linked to protein stability and folding via forming a disulfide bond, and Cys(6) and Cys(111) as free thiols. But the roles of the cellular oxidation-reduction (redox) environment in SOD1 folding and aggregation are not well understood. Here we explore the effects of cellular redox systems on the aggregation of hSOD1 proteins. We found that the known hSOD1 mutations G93A and A4V increased the capability of the thioredoxin and glutaredoxin systems to reduce hSOD1 compared with wild-type hSOD1. Treatment with inhibitors of these redox systems resulted in an increase of hSOD1 aggregates in the cytoplasm of cells transfected with mutants but not in cells transfected with wild-type hSOD1 or those containing a secondary C111G mutation. This aggregation may be coupled to changes in the redox state of the G93A and A4V mutants upon mild oxidative stress. These results strongly suggest that the thioredoxin and glutaredoxin systems are the key regulators for hSOD1 aggregation and may play critical roles in the pathogenesis of ALS. PMID- 27261464 TI - ESUS and INTERACT. PMID- 27261462 TI - 14-3-3sigma Gene Loss Leads to Activation of the Epithelial to Mesenchymal Transition Due to the Stabilization of c-Jun Protein. AB - Loss of 14-3-3sigma has been observed in multiple tumor types; however, the mechanisms by which 14-3-3sigma loss leads to tumor progression are not understood. The experiments in this report demonstrate that loss of 14-3-3sigma leads to a decrease in the expression of epithelial markers and an increase in the expression of mesenchymal markers, which is indicative of an induction of the epithelial to mesenchymal transition (EMT). The EMT was accompanied by an increase in migration and invasion in the 14-3-3sigma(-/-) cells. 14-3-3sigma(-/ ) cells show increased stabilization of c-Jun, resulting in an increase in the expression of the EMT transcription factor slug. 14-3-3sigma induces the ubiquitination and degradation of c-Jun in an FBW7-dependent manner. c-Jun ubiquitination is dependent on the presence of an intact nuclear export pathway as c-Jun is stabilized and localized to the nucleus in the presence of a nuclear export inhibitor. Furthermore, the absence of 14-3-3sigma leads to the nuclear accumulation and stabilization of c-Jun, suggesting that 14-3-3sigma regulates the subcellular localization of c-Jun. Our results have identified a novel mechanism by which 14-3-3sigma maintains the epithelial phenotype by inhibiting EMT and suggest that this property of 14-3-3sigma might contribute to its function as a tumor suppressor gene. PMID- 27261463 TI - The Structurally Plastic CH2 Domain Is Linked to Distinct Functions of Fimbrins/Plastins. AB - Fimbrins/plastins have been implicated in the generation of distinct actin structures, which are linked to different cellular processes. Historically, fimbrins/plastins were mainly considered as generating tight actin bundles. Here, we demonstrate that different members of the fimbrin/plastin family have diverged biochemically during evolution to generate either tight actin bundles or loose networks with distinct biochemical and biophysical properties. Using the phylogenetically and functionally distinct Arabidopsis fimbrins FIM4 and FIM5 we found that FIM4 generates both actin bundles and cross-linked actin filaments, whereas FIM5 only generates actin bundles. The distinct functions of FIM4 and FIM5 are clearly observed at single-filament resolution. Domain swapping experiments showed that cooperation between the conformationally plastic calponin homology domain 2 (CH2) and the N-terminal headpiece determines the function of the full-length protein. Our study suggests that the structural plasticity of fimbrins/plastins has biologically meaningful consequences, and provides novel insights into the structure-function relationship of fimbrins/plastins as well as shedding light on how cells generate distinct actin structures. PMID- 27261465 TI - Assistant Professor Dar Dowlatshahi. PMID- 27261466 TI - Corrigendum to an article by J David Spence. PMID- 27261468 TI - Mental health literacy in Hong Kong. AB - BACKGROUND AND AIMS: The aim of this study was to investigate Hong Kong nationals' ability to recognize 13 different mental disorders and to examine whether there may be a relationship between their mental health literacy (MHL) and their tendency to describe/explain symptoms of mental disorders in physical terms. METHODS: A total of 299 participants took part in this study and the vignettes depict post-traumatic stress disorder, depression, obsessive-compulsive disorder (OCD), dependent personality disorder, schizotypal personality disorder, generalized anxiety disorder, agoraphobia, bipolar disorder, social phobia, panic disorder, narcissistic personality disorder, schizophrenia and antisocial personality disorder. RESULTS: Overall, OCD was the best identified and the personality disorders were the worst. A significant negative correlation was found between participants' MHL and the rate of offering a 'physical' rather than a 'psychological' explanation. Some mental disorders were better recognized than others such as OCD (40.1%) and depression (36.3%). However, the majority of the other disorders were very poorly recognized and labelled with the rest having 'correct response' rates of lower than 15%. Over half of the mental disorders had 'correct' response rates of lower than 5%. CONCLUSION: In accordance with many other studies in the area, this study found Asian participants poor at recognizing mental disorders. This is probably due to the fact that mental illnesses of all kinds remain a taboo topic. PMID- 27261467 TI - A Phase II Trial of a Histone Deacetylase Inhibitor Panobinostat in Patients With Low-Grade Neuroendocrine Tumors. AB - LESSONS LEARNED: Pancreatic neuroendocrine tumors versus carcinoid tumors should be examined separately in clinical trials.Progression-free survival is more clinically relevant as the primary endpoint (rather than response rate) in phase II trials for low-grade neuroendocrine tumors. BACKGROUND: The most common subtypes of neuroendocrine tumors (NETs) are pancreatic islet cell tumors and carcinoids, which represent only 2% of all gastrointestinal malignancies. Histone deacetylase (HDAC) inhibitors have already been shown to suppress tumor growth and induce apoptosis in various malignancies. In NET cells, HDAC inhibitors have resulted in increased Notch1 expression and subsequent inhibition of growth. We present here a phase II study of the novel HDAC inhibitor panobinostat in patients with low-grade NET. METHODS: Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of <=2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. RESULTS: Fifteen patients were accrued, and 13 were evaluable for response. No responses were seen, but the stable disease rate was 100%. The median progression-free survival (PFS) was 9.9 months, and the median overall survival was 47.3 months. Fatigue (27%), thrombocytopenia (20%), diarrhea (13%), and nausea (13%) were the most common related grade 3 toxicities. There was one grade 4 thrombocytopenia (7%). These results did not meet the prespecified criteria to open the study to full accrual. CONCLUSION: The HDAC inhibitor panobinostat has a high stable disease rate and reasonable PFS in low-grade NET, but has a low response rate. PMID- 27261469 TI - The mental health of sexually trafficked female survivors in Nepal. AB - BACKGROUND: Despite further recent research into the consequences associated with human sex trafficking, scant evidence associated with the mental health outcomes among victims of sex trafficking remains, including within Nepal where trafficking continues to be a growing problem. AIM: To investigate the prevalence and explanatory factors of depression, anxiety and post-traumatic stress disorder (PTSD) symptoms among female survivors being housed and supported by two non governmental organisations (NGOs) in Nepal. METHODS: A total of 66 female sex trafficking survivors being housed by two NGOs were purposively sampled. Anxiety and depression symptomatology were measured using the Hopkins Symptoms Checklist 25 instrument and PTSD symptomatology was measured using the PTSD Checklist Civilian Version. RESULTS: In all, 87%, 85.5% and 29.7% of the sample scored above anxiety, depression and PTSD thresholds, respectively. HIV-positive status and length of workday during trafficking period significantly associated with at least one outcome measure. CONCLUSION: The results contribute further evidence of how damaging sex trafficking can be to victims, particularly in terms of being at risk of clinical depression and/or anxiety. Continued efforts to prevent trafficking from occurring as well as effective, timely intervention for survivors are needed. PMID- 27261470 TI - Reply to Naudet and Colleagues. Cost-Effectiveness in Health Technology Assessment-A Case in Alcohol Dependence. PMID- 27261471 TI - Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics. AB - AIMS: Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. METHODS: We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. RESULTS: A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. CONCLUSION: Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. SHORT SUMMARY: Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis. We studied 59 patients and found that liver function derangement, vitamin B12 and homocysteine levels are all independently related to brain atrophy assessed by computed tomography, although we found no association between these parameters and cognitive alterations. PMID- 27261472 TI - Underestimating the Alcohol Content of a Glass of Wine: The Implications for Estimates of Mortality Risk. AB - AIMS: Increases in glass sizes and wine strength over the last 25 years in the UK are likely to have led to an underestimation of alcohol intake in population studies. We explore whether this probable misclassification affects the association between average alcohol intake and risk of mortality from all causes, cardiovascular disease and cancer. METHODS: Self-reported alcohol consumption in 1997-1999 among 7010 men and women in the Whitehall II cohort of British civil servants was linked to the risk of mortality until mid-2015. A conversion factor of 8 g of alcohol per wine glass (1 unit) was compared with a conversion of 16 g per wine glass (2 units). RESULTS: When applying a higher alcohol content conversion for wine consumption, the proportion of heavy/very heavy drinkers increased from 28% to 41% for men and 15% to 28% for women. There was a significantly increased risk of very heavy drinking compared with moderate drinking for deaths from all causes and cancer before and after change in wine conversion; however, the hazard ratios were reduced when a higher wine conversion was used. CONCLUSIONS: In this population-based study, assuming higher alcohol content in wine glasses changed the estimates of mortality risk. We propose that investigator-led cohorts need to revisit conversion factors based on more accurate estimates of alcohol content in wine glasses. Prospectively, researchers need to collect more detailed information on alcohol including serving sizes and strength. SHORT SUMMARY: The alcohol content in a wine glass is likely to be underestimated in population surveys as wine strength and serving size have increased in recent years. We demonstrate that in a large cohort study, this underestimation affects estimates of mortality risk. Investigator-led cohorts need to revisit conversion factors based on more accurate estimates of alcohol content in wine glasses. PMID- 27261473 TI - Cost-Effectiveness of Nalmefene: Exaggerated Expectations or Fallacy? PMID- 27261474 TI - Italian Credit Mobility Students Significantly Increase Their Alcohol Intake, Risky Drinking and Related Consequences During the Study Abroad Experience. AB - AIMS: To examine changes in alcohol intake and consequences in Italian students studying abroad. METHODS: Italian exchange students planning to study abroad were invited to report on their drinking and alcohol-related negative consequences before and after their time abroad. RESULTS: After excluding those who abstained throughout, data on 121 students were analysed and showed that they tended to consume more alcohol and experience more alcohol-related negative consequences compared to their pre-departure levels. CONCLUSION: The added alcohol risk of study abroad for Italian students merits consideration of possible opportunities for intervention. PMID- 27261475 TI - Femoral Neck Stress Fracture: Can MRI Grade Help Predict Return-to-Running Time? AB - BACKGROUND: Limited research is available regarding return-to-running (RTR) time after femoral neck stress fractures. While studies have shown the prognostic value of image-based grading scales for stress fractures at other sites, few have included femoral neck stress fractures. PURPOSE: To determine if the grade of femoral neck stress fractures based on magnetic resonance imaging (MRI) characteristics correlates with RTR time. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included 24 patients (mean age, 32.9 years; range, 18-51 years) who were diagnosed with 27 femoral neck stress fractures by MRI from 2009 to 2015 at a single sports medicine clinic. All fractures were compression sided and were treated nonoperatively. Charts were reviewed for patient demographics and RTR time. Images were graded from 1 to 4 using the Arendt stress fracture severity scale. Statistical analysis was performed using survival analysis and Cox proportional hazard model to compare the RTR time between grades. Cox regression was repeated, adjusted for age, bone mineral density (BMD), and body mass index (BMI). RESULTS: The mean (+/-standard error of the mean) RTR time in weeks for patients with fractures graded 1 to 4 was 7.4 +/- 2.7 (range, 4-11), 13.8 +/- 3.8 (range, 6-21), 14.7 +/- 3.5 (range, 8.5-24), and 17.5 +/- 3.4 (range, 10-32), respectively. Survival analysis indicated that there was a statistically significant effect of fracture grade on RTR time (P = .0065). The Cox model indicated a statistically significant difference in RTR time between grades 1 and 2 (P = .036), 1 and 3 (P = .014), and 1 and 4 (P = .002). The unadjusted hazard ratio was significant (P = .037). There were no statistically significant differences between the remaining grades (P = .82 for grades 2 and 3, P = .37 for grades 2 and 4, and P = .31 for grades 3 and 4). Age (P = .71) and BMD (P = .81) did not have an effect on RTR time. The hazard ratio remained significant (P = .05) after adjusting for age and BMD. BMI tended to have an effect on RTR time (P = .09). After adding BMI to the adjustment, the hazard ratio decreased in significance (P = .13), although sample size also decreased. CONCLUSION: Grade 2 to 4 femoral neck stress fractures require longer RTR time than do grade 1 injuries. Patients with lower BMI tend to require a longer RTR time. PMID- 27261476 TI - Are Female Soccer Players at an Increased Risk of Second Anterior Cruciate Ligament Injury Compared With Their Athletic Peers? AB - BACKGROUND: Female soccer players have a well-known risk for anterior cruciate ligament (ACL) injury, but few studies have reported on second ACL injuries in this population. PURPOSE: To (1) report the rates of subsequent ACL injury (ipsilateral graft rupture or contralateral tear) in competitive female soccer players, (2) compare these rates with those of other female athletes of similar competitive level, (3) determine risk factors for second ACL injury, and (4) report clinical outcome scores in this population. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The medical records at a single institution were reviewed for female patients who were injured during a competitive athletic event and treated with primary ACL reconstruction (ACLR) between 1998 and 2013. Patients were followed for a mean of 68.8 months postoperatively (range, 24-115.2 months). Clinical outcome was obtained via Lysholm and International Knee Documentation Committee (IKDC) scores. Soccer players were matched 1:1 to non soccer athletes for age, activity level, and graft type. RESULTS: A total of 180 female ACLR patients with a mean +/- SD age of 19.6 +/- 6.9 years met the study inclusion and exclusion criteria (90 soccer players and 90 non-soccer players). Soccer players sustained more second ACL injuries, including both graft failures (11% vs 1%; P < .01) and contralateral ACL tears (17% vs 4%; P < .01), compared with non-soccer players. Of the 67 patients who returned to soccer after ACLR (mean age, 17.5 years; range, 13-27 years), significantly more had graft tears compared with those who did not return to soccer (15% vs 0%, respectively; P = .04); however, the difference in contralateral ACL tears (19% for returning players vs 9% for those who did not return; P = .34) was not significant. Relatively older age (odds ratio, 1.5 per year; P = .03) was a significant risk factor for ACL graft tear but not for contralateral ACL injury. Both groups had similar mean Lysholm (96 vs 95) and IKDC scores (95 vs 96) at final follow-up. CONCLUSION: Twenty-eight percent of all female soccer players and 34% of those players who returned to soccer had a second ACL tear. Soccer players had an increased rate of both graft tear and contralateral ACL injury compared with similar non-soccer athletes. Older age and return to soccer were significant risk factors for graft rupture. PMID- 27261479 TI - Something Old, Something New, Something Borrowed, Something Fused: Novel EGFR Rearrangements in Lung Adenocarcinomas. AB - Mutations in EGFR stand as the archetype for somatic alterations that lead to oncogene addiction and that predict for response to targeted therapies. In this issue of Cancer Discovery, Konduri and colleagues report on a pair of novel oncogenic and actionable EGFR fusion events in a series of patients with lung adenocarcinomas, casting new light on this model gene. Cancer Discov; 6(6); 574 5. (c)2016 AACRSee related article by Konduri et al., p. 601. PMID- 27261480 TI - Senescence Can Be BETter without the SASP? AB - Global remodeling of the chromatin landscape occurs during senescence, although its functional consequence is still unclear. In this issue, Tasdemir and colleagues show that the epigenetic regulator BRD4 is required for expression of the proinflammatory senescence-associated secretory phenotype and immune clearance of senescent cells in vitro and in vivo Their results could be useful in the design of novel therapies to treat aging-related diseases, including cancer.Cancer Discov; 6(6); 576-8. (c)2016 AACR.See related article by Tasdemir et al., p. 612. PMID- 27261481 TI - Forecasting Cytokine Storms with New Predictive Biomarkers. AB - T cells genetically modified with CD19 chimeric antigen receptors have produced impressive clinical responses in patients with refractory B-cell malignancies, but therapeutic responses are often accompanied by cytokine release syndrome (CRS), which can cause significant morbidity and mortality. Teachey and colleagues have identified predictive biomarkers for this complication that may allow testing of earlier intervention with agents such as the IL6 receptor blocker tocilizumab to evaluate whether CRS can be ameliorated without jeopardizing clinical responses. Cancer Discov; 6(6); 579-80. (c)2016 AACR.See related article by Teachey et al., p. 664. PMID- 27261483 TI - Exercise Training and Cognitive Rehabilitation: A Symbiotic Approach for Rehabilitating Walking and Cognitive Functions in Multiple Sclerosis? AB - The current review develops a rationale and framework for examining the independent and combined effects of exercise training and cognitive rehabilitation on walking and cognitive functions in persons with multiple sclerosis (MS). To do so, we first review evidence for improvements in walking and cognitive outcomes with exercise training and cognitive rehabilitation in MS. We then review evidence regarding cognitive-motor coupling and possible cross modality transfer effects of exercise training and cognitive rehabilitation. We lastly present a macro-level framework for considering mechanisms that might explain improvements in walking and cognitive dysfunction with exercise and cognitive rehabilitation individually and combined in MS. We conclude that researchers should consider examining the effects of exercise training and cognitive rehabilitation on walking, cognition, and cognitive-motor interactions in MS and the possible physiological and central mechanisms for improving these functions. PMID- 27261482 TI - So You Can Teach Old Fibroblasts New Tricks. AB - New data show that as dermal fibroblasts grow old, they increase their secretion of the WNT antagonist sFRP2 to drive melanoma cell metastasis. sFRP2 suppresses beta-catenin and MITF signaling in melanoma cells, downregulating the redox regulator APE1, making melanoma cells more sensitive to oxidative stress and driving resistance to BRAF inhibitors. Thus, the aging microenvironment in elderly patient skin activates a signaling pathway that drives more aggressive melanoma cell behavior. Cancer Discov; 6(6); 581-3. (c)2016 AACR. PMID- 27261484 TI - Recurrent transient ischemic attack as the initial manifestation of Takayasu arteritis. PMID- 27261485 TI - NGS-based molecular diagnosis of hereditary ataxia is cost-efficient: an illustrative family. PMID- 27261486 TI - Reply to recurrent transient ischemic attack as the initial manifestation of Takayasu arteritis. PMID- 27261487 TI - Eccentric target sign of cerebral toxoplasmosis. PMID- 27261488 TI - 'Epidemic' of hand deformities in the French Renaissance paintings of Jean and Francois Clouet. AB - This article analyses the nature of the multiple finger anomalies found in portraits by the French Renaissance artistic dynasty, the Clouets. The multiplicity of finger anomalies could be either innocent congenital variants, or pathological and traumatic deformities. In view of the presence of such 'beautifying variations' in the works of other Renaissance artists, the authors decided that these features were not the result of an epidemic of deformities, but instead represented a stylistic approach in paintings of this period at the French Court. PMID- 27261489 TI - Incidence, care quality and outcomes of patients with acute kidney injury in admitted hospital care. AB - BACKGROUND/INTRODUCTION: Acute kidney injury (AKI) is common in acute hospital admission and associated with worse patient outcomes. AIM: To measure incidence, care quality and outcome of AKI in admitted hospital care. DESIGN: Forty-six of 168 acute NHS healthcare trusts in UK caring for 2 million acute hospital admissions per annum collected information on adults identified with AKI stage 3 (3-fold rise in serum creatinine or creatinine >354 umol/l) through routine biochemical testing over a 5-month period in 2012. METHODS: Information was collected on patient and care characteristics. Primary outcomes were survival and recovery of kidney function at 1 month. RESULTS: A total of 15 647 patients were identified with biochemical AKI stage 3. Case note reviews were available for 7726 patients. In 80%, biochemical AKI stage 3 was confirmed clinically. Among this group, median age was 75 years, median length of stay was 12 days and the overall mortality within 1 month was 38%. Significant factors in a multivariable model predicting survival included age and some causes of AKI. Dipstick urinalysis, medication review, discussion with a nephrologist and acceptance for transfer to a renal unit were also associated with higher survival, but not early review by a senior doctor, acceptance for transfer to critical care or requirement for renal replacement therapy. Eighteen percent of people did not have their kidney function checked 1 month after the episode had resolved. DISCUSSION/CONCLUSIONS: This large study of in-hospital AKI supports the efficacy of biochemical detection of AKI in common usage. AKI mortality remains substantial, length of stay comparable with single-centre studies, and much of the variation is poorly explained (model Cox and Snell R2 = 0.131) from current predictors. PMID- 27261490 TI - Behavioral and neuronal determinants of negative reciprocity in the ultimatum game. AB - The rejection of unfair offers in the ultimatum game (UG) indicates negative reciprocity. The model of strong reciprocity claims that negative reciprocity reflects prosociality because the rejecting individual is sacrificing resources in order to punish unfair behavior. However, a recent study found that the rejection rate of unfair offers is linked to assertiveness (status defense model). To pursue the question what drives negative reciprocity, the present study investigated individual differences in the rejection of unfair offers along with their behavioral and neuronal determinants. We measured fairness preferences and event-related potentials (ERP) in 200 healthy participants playing a computerized version of the UG with pictures of unfair and fair proposers. Structural equation modeling (SEM) on the behavioral data corroborated both the strong reciprocity and the status defense models of human cooperation: Not only more prosocial but also more assertive individuals were more likely to show negative reciprocity by rejecting unfair offers. Experimental ERP results confirmed the feedback negativity (FN) as a neural signature of fairness processing. Multilevel SEM of brain-behavior relationships revealed that negative reciprocity was significantly associated with individual differences in FN amplitudes in response to proposers. Our results confirm stable individual differences in fairness processing at the behavioral and neuronal level. PMID- 27261491 TI - Gene Methylation and Cytological Atypia in Random Fine-Needle Aspirates for Assessment of Breast Cancer Risk. AB - Methods to determine individualized breast cancer risk lack sufficient sensitivity to select women most likely to benefit from preventive strategies. Alterations in DNA methylation occur early in breast cancer. We hypothesized that cancer-specific methylation markers could enhance breast cancer risk assessment. We evaluated 380 women without a history of breast cancer. We determined their menopausal status or menstrual cycle phase, risk of developing breast cancer (Gail model), and breast density and obtained random fine-needle aspiration (rFNA) samples for assessment of cytopathology and cumulative methylation index (CMI). Eight methylated gene markers were identified through whole-genome methylation analysis and included novel and previously established breast cancer detection genes. We performed correlative and multivariate linear regression analyses to evaluate DNA methylation of a gene panel as a function of clinical factors associated with breast cancer risk. CMI and individual gene methylation were independent of age, menopausal status or menstrual phase, lifetime Gail risk score, and breast density. CMI and individual gene methylation for the eight genes increased significantly (P < 0.001) with increasing cytological atypia. The findings were verified with multivariate analyses correcting for age, log (Gail), log (percent density), rFNA cell number, and body mass index. Our results demonstrate a significant association between cytological atypia and high CMI, which does not vary with menstrual phase or menopause and is independent of Gail risk and mammographic density. Thus, CMI is an excellent candidate breast cancer risk biomarker, warranting larger prospective studies to establish its utility for cancer risk assessment. Cancer Prev Res; 9(8); 673-82. (c)2016 AACR. PMID- 27261494 TI - Intersocietal Accreditation Commission. PMID- 27261493 TI - Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. AB - Improvements in the control of inflammation in rheumatoid arthritis (RA) by conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) have led to a substantial change in the clinical outcomes of patients during the last 30 years. Current treatment can lead to sustained remission in some patients raising questions about the optimal management strategies in this subgroup of patients. Today, tapering of DMARDs and even their discontinuation appears as an interesting concept for achieving a more tailored and dynamic treatment approach of RA, especially in patients, who achieved full disease control by DMARD treatment. In this review article, current developments of DMARD tapering are discussed. The article provides an overview of existing studies on this topic and addresses new strategies to reach drug-free remission. Furthermore, concepts for defining patients eligible for DMARD tapering are described and potential future strategies in using biomarkers in predicting the risk for disease relapse after initiation of DMARD tapering are addressed. These findings are finally considered in light of the vision to achieve cure as an ultimate goal in patients with RA achieving full control of inflammation. PMID- 27261495 TI - Being Passionate About Nuclear Medicine Technology. PMID- 27261492 TI - Are Hallucinations Due to an Imbalance Between Excitatory and Inhibitory Influences on the Brain? AB - This review from the International Consortium on Hallucinations Research intends to question the pertinence of the excitatory-to-inhibitory (E/I) imbalance hypothesis as a model for hallucinations. A large number of studies suggest that subtle impairments of the E/I balance are involved in neurological and psychiatric conditions, such as schizophrenia. Emerging evidence also points to a role of the E/I balance in maintaining stable perceptual representations, suggesting it may be a plausible model for hallucinations. In support, hallucinations have been linked to inhibitory deficits as shown with impairment of gamma-aminobutyric acid transmission, N-methyl-d-aspartate receptor plasticity, reductions in gamma-frequency oscillations, hyperactivity in sensory cortices, and cognitive inhibition deficits. However, the mechanisms by which E/I dysfunctions at the cellular level might relate to clinical symptoms and cognitive deficits remain unclear. Given recent data advances in the field of clinical neuroscience, it is now possible to conduct a synthesis of available data specifically related to hallucinations. These findings are integrated with the latest computational frameworks of hallucinations, and recommendations for future research are provided. PMID- 27261496 TI - Progress on Strategic Goals. PMID- 27261497 TI - Reducing cardiovascular risk factors in non-selected outpatients with schizophrenia. AB - OBJECTIVES: Cardiovascular diseases are the most common causes of premature death in patients with schizophrenia. We aimed at reducing cardiovascular risk factors in non-selected outpatients with schizophrenia using methods proven effective in short-term trials. Furthermore, we examined whether any baseline characteristics were associated with positive outcomes. METHODS: All outpatients treated for schizophrenia at two Danish hospitals were included in this 1-year follow-up study. The patients were offered health interventions both individually and in groups. Weight, waist circumference, blood glucose and lipids and information on smoking and alcohol were obtained. RESULTS: On average, small significant increases in body mass index (BMI) and waist circumferences were observed while small non-significant improvements in other cardiovascular risk factors were seen. Patients with high baseline BMI and patients with duration of treated illness beyond 2 years had significantly better intervention outcomes. CONCLUSION: Our results show that it was difficult to improve physical health in a group of non-selected patients with schizophrenia as part of routine care. The patients were not easily motivated to participate in the interventions, and it was difficult to monitor the recommended metabolic risk measures in the patient group. Future research should focus on simple strategies in health promotion that can be integrated into routine care. PMID- 27261499 TI - Factors Associated With Discrepancy in Parent-Teacher Reporting of Symptoms of ADHD in a Large Clinic-Referred Sample of Children. AB - OBJECTIVE: To identify factors associated with discrepancy in parent-teacher reporting of symptoms of ADHD. METHOD: Parents and teachers rated 1,364 children using an ADHD rating scale. Data were analyzed using multiple regressions and ANOVA. RESULTS: Demographic variables predicted greater parent-teacher discrepancy for ethnic minority families than for Caucasian families. Comorbidity variables predicted greater discrepancy for children who had a comorbid externalizing disorder. Academic performance variables predicted discrepancy for children who showed more homework problems. When all significant predictors were entered together, externalizing disorders and homework problems emerged as significant predictors. Participants whose parents reported higher levels of symptoms were of significantly higher socioeconomic status. Participants whose teachers reported higher levels of symptoms were significantly less likely to have a comorbid externalizing disorder and parent-reported homework problems. CONCLUSION: Parent-teacher discrepancies are likely to occur when the child has significant homework and externalizing behavior problems. PMID- 27261501 TI - Why patients with dementia need a motor examination. PMID- 27261502 TI - Acetylcholinesterase inhibitors are associated with weight loss in older people with dementia: a systematic review and meta-analysis. AB - We conducted a systematic review and meta-analysis investigating the influence of acetylcholinesterase inhibitors (AChEIs) therapy on nutritional status and weight across observational and interventional studies. Two authors searched major electronic databases from inception until 10/14/2015 for longitudinal, open-label and randomised double-blind placebo controlled (randomised controlled trials (RCTs)) studies of AChEIs in patients with dementia reporting nutritional status outcome data. Out of 3551 initial hits, 25 studies (12 open-label trials, 9 RCTs and 4 longitudinal studies) including 10 792 patients with dementia were meta analysed. In longitudinal studies (median follow-up 6 months), a significant cumulative incidence of weight loss between baseline and follow-up evaluation was observed (studies=2; 5%; 95% CI 1% to 34%, p<0.0001; I2=95%). These findings were confirmed in open-label trials (6%; 95% CI 4% to 7%, p<0.0001; I2=78%). In 9 RCTs (median follow-up 5 months), those taking AChEIs more frequently experienced weight loss than participants taking placebo (OR=2.18; 95% CI 1.50 to 3.17, p<0.0001; I2=29%). AChEIs therapy contributes to weight loss in patients with dementia, with a 2-fold increased risk observed in the meta-analysis of RCTs. Clinicians should carefully consider the benefit and risk of prescribing AChEIs. Nutritional status should be routinely evaluated in patients with dementia treated with AChEIs. PMID- 27261500 TI - Defining SOD1 ALS natural history to guide therapeutic clinical trial design. AB - IMPORTANCE: Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population. OBJECTIVE: To establish an updated natural history of ALSSOD1. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000. MAIN OUTCOMES AND MEASURES: Age of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis. RESULTS: Mean age of disease onset was 49.7+/-12.3 years (mean+/ SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6+/-6.0 and 1.4+/-0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p<0.0001, log-rank). A statistically significant increase in ALS-FRS decline in SOD1A4V compared with SOD1non-A4V participants (p=0.02) was observed, as well as a statistically significant increase in ALS-forced vital capacity decline in SOD1A4V compared with SOD1non-A4V (p=0.02). CONCLUSIONS AND RELEVANCE: SOD1A4V is an aggressive, but relatively homogeneous form of ALS. These SOD1-specific ALS natural history data will be important for the design and implementation of clinical trials in the ALSSOD1 patient population. PMID- 27261503 TI - Cerebral microbleeds and neuropsychiatric symptoms in an elderly Asian cohort. AB - OBJECTIVES: Neuropsychiatric symptoms (NPS) are commonly found in patients with cerebral small vessel disease such as white matter hyperintensities and lacunar infarcts. However, the association between cerebral microbleeds (CMBs) and NPS has not been examined. Hence the present study sought to investigate the relation between CMBs and NPS in an elderly population. METHODS: This is a cross-sectional study of elderly Asians living in the community, who were assessed on a comprehensive neuropsychological battery and underwent clinical examinations as well as brain MRI scans. The 12-item neuropsychiatric inventory (NPI) was administered to a reliable informant. Total scores for individual symptoms and for NPI global performance were calculated and compared across three groups: no CMB, presence of 1 CMB and presence of multiple CMBs, controlling for demographics, vascular risk factors and other MRI markers. RESULTS: A total of 802 participants were included in the analysis. Participants with multiple CMBs had higher NPI total score compared to those with no CMB (1.06 vs 2.66, p=0.03). On individual symptom scores, higher score on depression (0.16 vs 0.53, p=0.02) and disinhibition (0.01 vs 0.14, p=0.04) was found in those elderly with multiple CMBs, independent of demographic and vascular risk factors, history of stroke, and other small vessel and large vessel disease markers. CONCLUSIONS: The presence of multiple CMBs is associated with high global neuropsychiatric disorder burden, in particular symptoms of depression and disinhibition. Future studies are recommended to investigate the importance of CMBs in the pathogenesis and longitudinal progression of neuropsychiatric disorders in the general elderly population. PMID- 27261504 TI - Design and Reporting of Targeted Anticancer Preclinical Studies: A Meta-Analysis of Animal Studies Investigating Sorafenib Antitumor Efficacy. AB - The validity of preclinical studies of candidate therapeutic agents has been questioned given their limited ability to predict their fate in clinical development, including due to design flaws and reporting bias. In this study, we examined this issue in depth by conducting a meta-analysis of animal studies investigating the efficacy of the clinically approved kinase inhibitor, sorafenib. MEDLINE, Embase, and BIOSIS databases were searched for all animal experiments testing tumor volume response to sorafenib monotherapy in any cancer published until April 20, 2012. We estimated effect sizes from experiments assessing changes in tumor volume and conducted subgroup analyses based on prespecified experimental design elements associated with internal, construct, and external validity. The meta-analysis included 97 experiments involving 1,761 animals. We excluded 94 experiments due to inadequate reporting of data. Design elements aimed at reducing internal validity threats were implemented only sporadically, with 66% reporting animal attrition and none reporting blinded outcome assessment or concealed allocation. Anticancer activity against various malignancies was typically tested in only a small number of model systems. Effect sizes were significantly smaller when sorafenib was tested against either a different active agent or combination arm. Trim and fill suggested a 37% overestimation of effect sizes across all malignancies due to publication bias. We detected a moderate dose-response in one clinically approved indication, hepatocellular carcinoma, but not in another approved malignancy, renal cell carcinoma, or when data were pooled across all malignancies tested. In support of other reports, we found that few preclinical cancer studies addressed important internal, construct, and external validity threats, limiting their clinical generalizability. Our findings reinforce the need to improve guidelines for the design and reporting of preclinical cancer studies. Cancer Res; 76(16); 4627-36. (c)2016 AACR. PMID- 27261505 TI - A Radiotracer Strategy to Quantify PARP-1 Expression In Vivo Provides a Biomarker That Can Enable Patient Selection for PARP Inhibitor Therapy. AB - Despite the availability of PARP inhibitors for cancer therapy, a biomarker to clearly stratify patients for selection of this treatment remains lacking. Here we describe a radiotracer-based method that addresses this issue, using the novel compound [(125)I] KX1: as a PARP-1-selective radiotracer that can accurately measure PARP-1 expression in vitro and in vivo The pharmacologic properties of the PARP radiotracer [(125)I] KX1: was characterized in multiple cell lines where single-agent sensitivity was correlated with [(125)I] KX1: binding to PARP-1. In vivo evaluation of [(125)I] KX1: verified in vitro results, validating PARP radiotracers to define PARP-1 enzyme expression as an in vivo biomarker. Notably, PARP-1 expression as quantified by [(125)I] KX1: correlated positively with the cytotoxic sensitivity of cell lines evaluated with PARP inhibitors. Overall, our results defined a novel technology with the potential to serve as a companion diagnostic to identify patients most likely to respond therapeutically to a PARP inhibitor. Cancer Res; 76(15); 4516-24. (c)2016 AACR. PMID- 27261506 TI - Incipient Melanoma Brain Metastases Instigate Astrogliosis and Neuroinflammation. AB - Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to the brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and the interactions of disseminated metastatic cells with the brain microenvironment are largely unknown. To study the hallmarks of brain metastatic niche formation, we established a transplantable model of spontaneous melanoma brain metastasis in immunocompetent mice and developed molecular tools for quantitative detection of brain micrometastases. Here we demonstrate that micrometastases are associated with instigation of astrogliosis, neuroinflammation, and hyperpermeability of the blood-brain barrier. Furthermore, we show a functional role for astrocytes in facilitating initial growth of melanoma cells. Our findings suggest that astrogliosis, physiologically instigated as a brain tissue damage response, is hijacked by tumor cells to support metastatic growth. Studying spontaneous melanoma brain metastasis in a clinically relevant setting is the key to developing therapeutic approaches that may prevent brain metastatic relapse. Cancer Res; 76(15); 4359-71. (c)2016 AACR. PMID- 27261507 TI - Definition of a Novel Feed-Forward Mechanism for Glycolysis-HIF1alpha Signaling in Hypoxic Tumors Highlights Aldolase A as a Therapeutic Target. AB - The hypoxia-inducible transcription factor HIF1alpha drives expression of many glycolytic enzymes. Here, we show that hypoxic glycolysis, in turn, increases HIF1alpha transcriptional activity and stimulates tumor growth, revealing a novel feed-forward mechanism of glycolysis-HIF1alpha signaling. Negative regulation of HIF1alpha by AMPK1 is bypassed in hypoxic cells, due to ATP elevation by increased glycolysis, thereby preventing phosphorylation and inactivation of the HIF1alpha transcriptional coactivator p300. Notably, of the HIF1alpha-activated glycolytic enzymes we evaluated by gene silencing, aldolase A (ALDOA) blockade produced the most robust decrease in glycolysis, HIF-1 activity, and cancer cell proliferation. Furthermore, either RNAi-mediated silencing of ALDOA or systemic treatment with a specific small-molecule inhibitor of aldolase A was sufficient to increase overall survival in a xenograft model of metastatic breast cancer. In establishing a novel glycolysis-HIF-1alpha feed-forward mechanism in hypoxic tumor cells, our results also provide a preclinical rationale to develop aldolase A inhibitors as a generalized strategy to treat intractable hypoxic cancer cells found widely in most solid tumors. Cancer Res; 76(14); 4259-69. (c)2016 AACR. PMID- 27261508 TI - Melanoma Lesions Independently Acquire T-cell Resistance during Metastatic Latency. AB - Melanoma often recurs after a latency period of several years, presenting a T cell-edited phenotype that reflects a role for CD8(+) T cells in maintaining metastatic latency. Here, we report an investigation of a patient with multiple recurrent lesions, where poorly immunogenic melanoma phenotypes were found to evolve in the presence of autologous tumor antigen-specific CD8(+) T cells. Melanoma cells from two of three late recurrent metastases, developing within a 6 year latency period, lacked HLA class I expression. CD8(+) T cell-resistant, HLA class I-negative tumor cells became clinically apparent 1.5 and 6 years into stage IV disease. Genome profiling by SNP arrays revealed that HLA class I loss in both metastases originated from a shared chromosome 15q alteration and independently acquired focal B2M gene deletions. A third HLA class I haplotype deficient lesion developed in year 3 of stage IV disease that acquired resistance toward dominant CD8(+) T-cell clonotypes targeting stage III tumor cells. At an early stage, melanoma cells showed a dedifferentiated c-Jun(high)/MITF(low) phenotype, possibly associated with immunosuppression, which contrasted with a c Jun(low)/MITF(high) phenotype of T cell-edited tumor cells derived from late metastases. In summary, our work shows how tumor recurrences after long-term latency evolve toward T-cell resistance by independent genetic events, as a means for immune escape and immunotherapeutic resistance. Cancer Res; 76(15); 4347-58. (c)2016 AACR. PMID- 27261509 TI - DNMT1 Inhibition Reprograms Pancreatic Cancer Stem Cells via Upregulation of the miR-17-92 Cluster. AB - Pancreatic ductal adenocarcinoma (PDAC) and other carcinomas are hierarchically organized, with cancer stem cells (CSC) residing at the top of the hierarchy, where they drive tumor progression, metastasis, and chemoresistance. As CSC and non-CSC share an identical genetic background, we hypothesize that differences in epigenetics account for the striking functional differences between these two cell populations. Epigenetic mechanisms, such as DNA methylation, play an important role in maintaining pluripotency and regulating the differentiation of stem cells, but the role of DNA methylation in pancreatic CSC is obscure. In this study, we investigated the genome-wide DNA methylation profile of PDAC CSC, and we determined the importance of DNA methyltransferases for CSC maintenance and tumorigenicity. Using high-throughput methylation analysis, we discovered that sorted CSCs have a higher level of DNA methylation, regardless of the heterogeneity or polyclonality of the CSC populations present in the tumors analyzed. Mechanistically, CSC expressed higher DNMT1 levels than non-CSC. Pharmacologic or genetic targeting of DNMT1 in CSCs reduced their self-renewal and in vivo tumorigenic potential, defining DNMT1 as a candidate CSC therapeutic target. The inhibitory effect we observed was mediated in part through epigenetic reactivation of previously silenced miRNAs, in particular the miR-17-92 cluster. Together, our findings indicate that DNA methylation plays an important role in CSC biology and also provide a rationale to develop epigenetic modulators to target CSC plasticity and improve the poor outcome of PDAC patients. Cancer Res; 76(15); 4546-58. (c)2016 AACR. PMID- 27261511 TI - Erratum: Cemento-ossifying fibroma of the jaw. PMID- 27261510 TI - MSH2 Dysregulation Is Triggered by Proinflammatory Cytokine Stimulation and Is Associated with Liver Cancer Development. AB - Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here, we demonstrated that TNFalpha stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via NF-kappaB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2(-) (/) (-)AID(+), ALB-MSH2(-) (/) (-), and ALB-AID(+) mice, in which MSH2 is deficient and/or activation-induced cytidine deaminase (AICDA) is expressed in cells with albumin producing hepatocytes. The mutation signatures in the tumors developed in these models, especially ALB-MSH2(-) (/) (-)AID(+) mice, closely resembled those of human hepatocellular carcinoma. Our findings demonstrated that inflammation mediated dysregulation of MSH2 may be a mechanism of genetic alterations during hepatocarcinogenesis. Cancer Res; 76(15); 4383-93. (c)2016 AACR. PMID- 27261512 TI - Radiological presentation of Pneumocystis jiroveci pneumonia mimicking bacterial pneumonia. PMID- 27261513 TI - Severe tumefactive rebound of multiple sclerosis following fingolimod cessation. PMID- 27261514 TI - Diagnostic Accuracy of 18F-FDG PET/CT in Infective Endocarditis and Implantable Cardiac Electronic Device Infection: A Cross-Sectional Study. AB - : Early diagnosis of infective endocarditis (IE) is based on the yielding of blood cultures and echocardiographic findings. However, they have limitations and sometimes the diagnosis is inconclusive, particularly in patients with prosthetic valves (PVs) and implantable cardiac electronic devices (ICEDs). The primary aim of this study was to evaluate the diagnostic accuracy of 18F-FDG PET/CT in patients with suspected IE and ICED infection. METHODS: A prospective study with 80 consecutive patients with suspected IE and ICED infection (65 men and 15 women with a mean age of 68 +/- 13 y) between June 2013 and May 2015 was performed in our hospital. The inclusion criteria were clinically suspected IE and ICED infection at the following locations: native valve (NV) (n = 21), PV (n = 29), or ICED (n = 30) (automatic implantable defibrillator [n = 11] or pacemaker [n = 19]). Whole-body 18F-FDG PET/CT with a myocardial uptake suppression protocol with unfractionated heparin was performed in all patients. The final diagnosis of infection was established by the IE Study Group according to the clinical, echocardiographic, and microbiologic findings. RESULTS: A final diagnosis of infection was confirmed in 31 patients: NV (n = 6), PV (n = 12), and ICED (n = 13). Sensitivity, specificity, positive predictive value, and negative predictive value for 18F-FDG PET/CT were 82%, 96%, 94%, and 87%, respectively. 18F-FDG PET/CT was false-negative in all cases with infected NV. 18F-FDG PET/CT was able to reclassify 63 of 70 (90%) patients initially classified as possible IE by modified Duke criteria. In 18 of 70 cases, 18F-FDG PET/CT changed possible to definite IE (26%) and in 45 of 70 cases changed possible to rejected IE (64%). Additionally, 18F-FDG PET/CT identified 8 cases of septic embolism and 3 of colorectal cancer in patients with a final diagnosis of IE. CONCLUSION: 18F-FDG PET/CT proved to be a useful diagnostic tool in suspected IE and ICED infection and should be included in the diagnostic algorithm for early diagnosis. 18F-FDG PET/CT is not useful in the diagnosis of IE in NV but should be also considered in the initial assessment of this complex scenario to rule out extracardiac complications and possible neoplasms. PMID- 27261515 TI - Multiscale Texture Analysis: From 18F-FDG PET Images to Histologic Images. AB - : Characterizing tumor heterogeneity using texture indices derived from PET images has shown promise in predicting treatment response and patient survival in some types of cancer. Yet, the relationship between PET-derived texture indices, precise tracer distribution, and biologic heterogeneity needs to be clarified. We investigated this relationship using PET images, autoradiographic images, and histologic images. METHODS: Three mice bearing orthotopically implanted mammary tumors derived from transgenic MMTV-PyMT mice were scanned with 18F-FDG PET/CT. The tumors were then sliced, and the slices were imaged with autoradiography and stained with hematoxylin and eosin. Six texture indices derived from the PET images, autoradiographic images, and histologic images were compared for their ability to capture heterogeneity on different scales. RESULTS: The PET-derived indices correlated significantly with the autoradiography-derived ones (R = 0.57 0.85), but the values differed in magnitude. The histology-derived indices correlated poorly with the autoradiography- and PET-derived ones (R = 0.06-0.54). All indices were slightly to moderately influenced by the difference in voxel size and spatial resolution in the autoradiographic images. The autoradiography derived indices differed significantly (P < 0.05) between regions with a high density of cells and regions with a low density and between regions with different spatial arrangements of cells. CONCLUSION: Heterogeneity derived in vivo from PET images accurately reflects the heterogeneity of tracer uptake derived ex vivo from autoradiographic images. Various tumor-cell densities and spatial cell distributions seen on histologic images can be distinguished using texture indices derived from autoradiographic images despite the difference in voxel size and spatial resolution. Yet, tumor texture derived from PET images only coarsely reflects the spatial distribution and density of tumor cells. PMID- 27261517 TI - Getting the Most out of 18F-FDG PET Scans: The Predictive Value of 18F-FDG PET Derived Blood Flow Estimates for Breast Cancer. PMID- 27261516 TI - Reduced Periprocedural Analgesia After Replacement of Water for Injection with Glucose 5% Solution as the Infusion Medium for 90Y-Resin Microspheres. AB - : The primary aim of our study was to compare the need for periinterventional on demand analgesia when water for injection (WFI) was replaced with glucose 5% (G5) for 90Y-resin microsphere administration. METHODS: Forty-one patients who received 77 radioembolization procedures with G5 (2014-2015) were retrospectively matched with 41 patients (77 radioembolization procedures) who received radioembolization with WFI (2011-2014) at our center. The need for on-demand pain medication was chosen as an objective and accessible measure of periprocedural pain experienced by patients. RESULTS: Patients were well matched according to sex, age, tumor type and involvement, and prior antiangiogenic therapies. Periinterventional analgesic requirements were significantly lower for radioembolization procedures performed with G5 than WFI: 5 of 77 (6.5%) versus 29 of 77 (37.7%), P <= 0,001, respectively. Early stasis (defined as slowed antegrade flow, before total vascular stasis) occurred in 12 of 154 (7.8%) radioembolization procedures overall and was not different (P <= 0.229) between the 2 groups (4/77 [5.2%] vs. 8/77 [10.4%]). CONCLUSION: Slow pulsatile administration of 90Y-resin microspheres with WFI is associated with a low rate of stasis. Replacement of WFI with G5 significantly reduces the need for periprocedural analgesia. These data favor the use G5 for 90Y-resin microsphere implantation in daily practice. PMID- 27261518 TI - 18F-FDG PET/CT in the Diagnostic Workup of Infective Endocarditis and Related Intracardiac Prosthetic Material: A Clear Message. PMID- 27261519 TI - Remodeling the Vascular Microenvironment of Glioblastoma with alpha-Particles. AB - : Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted alpha-particle therapy with 225Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225Ac-E4G10. METHODS: We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. RESULTS: The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor associated edema and necrosis were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after alpha-particle therapy. CONCLUSION: Targeted antivascular alpha-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of platelet-derived growth factor-driven glioblastoma. PMID- 27261520 TI - 68Ga-PSMA PET/CT Detects the Location and Extent of Primary Prostate Cancer. AB - : We evaluated the accuracy of PET/CT with 68Ga-PSMA-HBED-CC-a 68Ga-conjugated ligand of human prostate-specific membrane antigen (PSMA)-to localize cancer in the prostate and surrounding tissue at initial diagnosis. METHODS: Twenty-one patients with biopsy-proven prostate cancer underwent 68Ga-PSMA-HBED-CC (68Ga PSMA) PET/CT at a median of 4 d (range, 0-47 d) before radical prostatectomy. Based on a 6-segment model, the Gleason score and proportion of tumor tissue within each segment (segmental tumor burden, or STB) as determined by histopathology (STBHP) were correlated with SUVmax and STB as determined by different SUV cutoffs for 68Ga-PSMA PET (STBPET1-6). Furthermore, the involvement of seminal vesicles and other extracapsular extension were assessed by histopathology and PET/CT. RESULTS: Histopathology-positive segments (n = 100 of 126; 79%) demonstrated a significantly higher mean +/- SD SUVmax (11.8 +/- 7.6) than histopathology-negative segments (4.9 +/- 2.9; P < 0.001). Receiver operating-characteristic analysis revealed an optimal SUVmax cutoff of 6.5 for discrimination of histopathology-positive segments from histopathology-negative segments (area under the curve, 0.84; P < 0.001), which gave 67% sensitivity, 92% specificity, a 97% positive predictive value, a 42% negative predictive value, and 72% accuracy. STBPET3 as determined by (2 * blood SUV) + (2 * SD) correlated best with STBHP (Pearson rho = 0.68; P < 0.001; mean difference +/- SD, 19% +/- 15%). PET/CT correctly detected invasion of seminal vesicles (n = 11 of 21 patients; 52%) with 86% accuracy and tumor spread through the capsule (n = 12; 57%) with 71% accuracy. CONCLUSION: 68Ga-PSMA PET/CT accurately detected the location and extent of primary prostate cancer. Our preliminary findings warrant further investigation of 68Ga-PSMA PET/CT in conjunction with needle biopsy. PMID- 27261521 TI - Parametric Binding Images of the TSPO Ligand 18F-DPA-714. AB - : 18F-labeled N,N-diethyl-2-(2-[4-(2-fluoroethoxy)phenyl]-5,7 dimethylpyrazolo[1,5-alpha]pyrimidine-3-yl)acetamide (DPA-714) is a radioligand for the 18-kDa translocator protein. The purpose of the present study was to identify the best method for generating quantitative parametric images of 18F-DPA 714 binding. METHODS: Ninety-minute dynamic 18F-DPA-714 PET scans with full arterial sampling from 6 healthy subjects and 9 Alzheimer disease (AD) patients were used. Plasma-input-based Logan graphical analysis and spectral analysis were used to generate parametric volume of distribution (VT) images. Five versions of Ichise, reference Logan, and 2 basis function implementations (receptor parametric mapping and simplified reference tissue model 2 [SRTM2]) of SRTM, all using gray matter cerebellum as the reference region, were applied to generate nondisplaceable binding potential (BPND) images. RESULTS: Plasma-input Logan analysis (r2 = 0.99; slope, 0.88) and spectral analysis (r2 = 0.99, slope, 0.93) generated estimates of VT that correlated well with values obtained using nonlinear regression. BPND values generated using SRTM2 (r2 = 0.83; slope, 0.95) and reference Logan analysis (r2 = 0.88; slope, 1.01) correlated well with nonlinear regression-based estimates. CONCLUSION: Both Logan analysis and spectral analysis can be used to obtain quantitatively accurate VT images of 18F DPA-714. In addition, SRTM2 and reference Logan analysis can provide accurate BPND images. These parametric images could be used for voxel-based comparisons. PMID- 27261522 TI - New Fetal Dose Estimates from 18F-FDG Administered During Pregnancy: Standardization of Dose Calculations and Estimations with Voxel-Based Anthropomorphic Phantoms. AB - : Data from the literature show that the fetal absorbed dose from 18F-FDG administration to the pregnant mother ranges from 0.5E-2 to 4E-2 mGy/MBq. These figures were, however, obtained using different quantification techniques and with basic geometric anthropomorphic phantoms. The aim of this study was to refine the fetal dose estimates of published as well as new cases using realistic voxel-based phantoms. METHODS: The 18F-FDG doses to the fetus (n = 19; 5-34 wk of pregnancy) were calculated with new voxel-based anthropomorphic phantoms of the pregnant woman. The image-derived fetal time-integrated activity values were combined with those of the mothers' organs from the International Commission on Radiological Protection publication 106 and the dynamic bladder model with a 1-h bladder-voiding interval. The dose to the uterus was used as a proxy for early pregnancy (up to 10 wk). The time-integrated activities were entered into OLINDA/EXM 1.1 to derive the dose with the classic anthropomorphic phantoms of pregnant women, then into OLINDA/EXM 2.0 to assess the dose using new voxel-based phantoms. RESULTS: The average fetal doses (mGy/MBq) with OLINDA/EXM 2.0 were 2.5E-02 in early pregnancy, 1.3E-02 in the late part of the first trimester, 8.5E 03 in the second trimester, and 5.1E-03 in the third trimester. The differences compared with the doses calculated with OLINDA/EXM 1.1 were +7%, +70%, +35%, and 8%, respectively. CONCLUSION: Except in late pregnancy, the doses estimated with realistic voxelwise anthropomorphic phantoms are higher than the doses derived from old geometric phantoms. The doses remain, however, well below the threshold for any deterministic effects. Thus, pregnancy is not an absolute contraindication of a clinically justified 18F-FDG PET scan. PMID- 27261523 TI - Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third Generation In Vivo Marker of Human Translocator Protein. AB - : Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide (18F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18F-GE180 PET in (older) healthy controls. METHODS: Ten healthy controls, 6 TSPO high affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. RESULTS: 18F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (VT) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a VT highly consistent with VT in the kinetic model, which could be used for voxelwise analysis. CONCLUSION: We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps. Although these control subjects have shown relatively low VT, the methodology presented here forms the basis for quantification for future PET studies using 18F-GE180 in different pathologies. PMID- 27261524 TI - Value of 68Ga-PSMA HBED-CC PET for the Assessment of Lymph Node Metastases in Prostate Cancer Patients with Biochemical Recurrence: Comparison with Histopathology After Salvage Lymphadenectomy. AB - : The purpose of this study was to evaluate the accuracy of Glu-NH-CO-NH-Lys (Ahx)-[68Ga(HBED-CC)] PET compared with morphologic imaging for the assessment of lymph node metastases (LNM) in patients with recurrent prostate cancer. METHODS: Forty-eight patients (median age, 71 y; interquartile range, 66-74 y) with biochemical recurrence (median prostate-specific antigen level, 1.31 ng/mL; interquartile range, 0.75-2.55 ng/mL) who underwent 68Ga-prostate-specific membrane antigen (PSMA) HBED-CC PET/CT or PET/MR and salvage lymphadenectomy were retrospectively included. Institutional review board approval and written informed consent were obtained from all patients for the purpose of anonymized evaluation and publication of their data. Standardized predefined lymph node (LN) template fields (n = 10) were evaluated in 68Ga-PSMA HBED-CC PET and morphologic imaging for the presence of LNM using a 5-point-scale. Additionally, SUVmean/max and size of suspicious lesions were determined. Specificity of 68Ga-PSMA HBED-CC PET imaging for PET-positive LNs was defined by comparison to histopathology. The diagnostic accuracy of 68Ga-PSMA HBED-CC PET compared with morphologic imaging alone was assessed, and areas under the receiver-operating-characteristic curves are presented. RESULTS: LNM were found histologically in 68 of 179 resected anatomic LN fields (38.0%). The specificity of 68Ga-PSMA HBED-CC PET and morphologic imaging was 97.3% and 99.1%, respectively. However, 68Ga-PSMA HBED-CC PET detected LNM in 53 of 68 histopathologically proven metastatic LN fields (77.9%) whereas morphologic imaging was positive in only 18 of 67 (26.9%). 68Ga PSMA HBED-CC PET imaging performed significantly superior to morphologic imaging for detection of LNM (difference in the areas under the receiver-operating characteristic curves, 0.139; 95% confidence interval, 0.063-0.214; P < 0.001). In 68Ga-PSMA HBED-CC PET, the mean size of PET-positive LN measured by CT or MRI was 8.3 +/- 4.3 mm (range, 4-25 mm), and LNs, which were suspicious only in CT or MRI, presented with a mean size of 13.0 +/- 4.9 mm (range, 8-25 mm). CONCLUSION: 68Ga-PSMA HBED-CC PET imaging is a promising method for early detection of LNM in patients with biochemical recurrent prostate cancer. It is more accurate than morphologic imaging and thus might represent a valuable tool for guiding salvage lymphadenectomy. PMID- 27261525 TI - The N-Methyl d-Aspartate Glutamate Receptor Antagonist Ketamine Disrupts the Functional State of the Corticothalamic Pathway. AB - The non-competitive N-methyl d-aspartate glutamate receptor (NMDAR) antagonist ketamine elicits a brain state resembling high-risk states for developing psychosis and early stages of schizophrenia characterized by sensory and cognitive deficits and aberrant ongoing gamma (30-80 Hz) oscillations in cortical and subcortical structures, including the thalamus. The underlying mechanisms are unknown. The goal of the present study was to determine whether a ketamine induced psychotic-relevant state disturbs the functional state of the corticothalamic (CT) pathway. Multisite field recordings were performed in the somatosensory CT system of the sedated rat. Baseline activity was challenged by activation of vibrissa-related prethalamic inputs. The sensory-evoked thalamic response was characterized by a short-latency (~4 ms) prethalamic-mediated negative sharp potential and a longer latency (~10 ms) CT-mediated negative potential. Following a single subcutaneous injection of ketamine (2.5 mg/kg), spontaneously occurring and sensory-evoked thalamic gamma oscillations increased and decreased in power, respectively. The power of the sensory-related gamma oscillations was positively correlated with both the amplitude and the area under the curve of the corresponding CT potential but not with the prethalamic potential. The present results show that the layer VI CT pathway significantly contributes in thalamic gamma oscillations, and they support the hypothesis that reduced NMDAR activation disturbs the functional state of CT and corticocortical networks. PMID- 27261526 TI - Host Habitat Volatiles Enhance the Olfactory Response of the Larval Parasitoid Holepyris sylvanidis to Specifically Host-Associated Cues. AB - Host foraging of parasitic wasps attacking insects living in stored food may be guided by volatile cues emanating from these postharvest products. However, little knowledge is available as to how habitat odor released from noninfested stored food affects the parasitoid's response to host-specific chemicals. In this study, we investigated the impact of wheat grist odor on the olfactory host search by the ectoparasitoid Holepyris sylvanidis This parasitoid attacks larvae of the confused flour beetle Tribolium confusum, a common pest of grain products. Olfactometer bioassays showed that female H. sylvanidis were attracted by volatiles released from host larval feces, whereas odor of noninfested wheat grist was neither attractive nor did it mask the host-indicating cues. We analyzed the odor of host larval feces and wheat grist by coupled gaschromatography-mass spectrometry and recorded the parasitoid's electroantennographic (EAG) responses to the detected volatiles. Two specifically host-associated components of the fecal odor, (E)-2-nonenal and 1-pentadecene, elicited strong EAG responses. Both components were attractive when tested individually, but less than larval feces. Attraction of parasitoids to these host specific key compounds was enhanced by addition of (i) noninfested habitat substrate odor or (ii) a blend of 3 EAG-active (but not behaviorally active) volatiles that had been identified in odor of noninfested grist (benzaldehyde, 1 tetradecene, 1-hexadecene), but were also detected in the host fecal odor. The impact of these volatiles ubiquitously released in a food store by noninfested habitat substrate on the parasitoid's orientation to host-specific volatile cues is discussed. PMID- 27261527 TI - Simultaneous Determination of Genotoxic Impurities in Fudosteine Drugs by GC-MS. AB - A simple, sensitive and reliable gas chromatography mass spectrometry (GC-MS) method has been developed, optimized and validated for the simultaneous determination of 3-chloro-1-propanol (CHP), 1,3-dichloropropane (DCP), 3 chloropropylacetate (CPA) and chloropropyl hydroxypropyl ether (CHE) contents in fudosteine, using chlorobenzene as internal standard. Efficient chromatographic separations were achieved on an Agilent J&W DB-WAXetr, 30 m long with 0.32 mm i.d., 1.0 um particle diameter column that consists of bonded and cross-linked polyethylene glycol as a stationary phase by passing helium as the carrier gas. The analytes were extracted in dichloromethane and monitored by gas chromatography electron ionization mass spectrometry (GC-EI-MS) with selective ion monitoring (SIM) mode. The performance of the method was assessed by evaluating specificity, precision (repeatability and reproducibility), sensitivity, linearity and accuracy. The limit of detection and limit of quantification established for CHP, DCP, CPA and CHE were in the range of 0.05 0.08 ug mL(-1) and 0.10-0.17 ug mL(-1), respectively. The recoveries for CHP, DCP, CPA and CHE were in the range of 92.0-101.5%. The results proved that the method is suitable for the simultaneous determination of contents of CHP, DCP, CPA and CHE in fudosteine. PMID- 27261528 TI - Astrocyte resilience to oxidative stress induced by insulin-like growth factor I (IGF-I) involves preserved AKT (protein kinase B) activity. PMID- 27261529 TI - Ambient temperature as a trigger of preterm delivery in a temperate climate. AB - BACKGROUND: Recent evidence suggests that elevated ambient temperatures may trigger preterm delivery. Since results from studies in temperate climates are inconclusive, we investigated the association between temperature and the risk of preterm birth in Flanders (Belgium). METHODS: We used data on 807 835 singleton deliveries (January 1998-July 2011). We combined a quasi-Poisson model with distributed lag non-linear models to allow for delayed and non-linear temperature effects, accounting for the daily pregnancies at risk and their gestational age distribution. RESULTS: For moderate heat (95th vs 50th centile) up to 1 day before delivery (lag 0-1), the risk of preterm birth increased by 8.5% (95% CI 2.4% to 15.0%) when minimum temperature increased from 8.3 degrees C to 16.3 degrees C and by 9.6% (95% CI 1.1% to 18.7%) when maximum temperature increased from 14.7 degrees C to 26.5 degrees C. Corresponding estimates for extreme heat (99th vs 50th centile) were 15.6% (95% CI 4.8% to 27.6%) for minimum temperature (19.0 degrees C vs 8.3 degrees C) and 14.5% (95% CI 0.5% to 30.6%) for maximum temperature (30.7 degrees C vs 14.7 degrees C). Despite the increased risk of preterm birth associated with cold at lag 2 (and lag 1 for minimum temperature), cumulative cold effects were small. The per cent change in preterm birth associated with moderate cold (5th vs 50th centile) up to 3 days before delivery (lag 0-3) was 2.1% (95% CI -4.1% to 8.7%) for minimum temperature (-2.0 degrees C vs 8.3 degrees C) and 0.6% (95% CI -7.3% to 9.2%) for maximum temperature (2.5 degrees C vs 14.7 degrees C). CONCLUSIONS: Even in a temperate climate, ambient temperature may trigger preterm delivery, suggesting that pregnant women should avoid temperature extremes. PMID- 27261530 TI - Molecular functions of the transcription factors E2A and E2-2 in controlling germinal center B cell and plasma cell development. AB - E2A is an essential regulator of early B cell development. Here, we have demonstrated that E2A together with E2-2 controlled germinal center (GC) B cell and plasma cell development. As shown by the identification of regulated E2A,E2-2 target genes in activated B cells, these E-proteins directly activated genes with important functions in GC B cells and plasma cells by inducing and maintaining DNase I hypersensitive sites. Through binding to multiple enhancers in the Igh 3' regulatory region and Aicda locus, E-proteins regulated class switch recombination by inducing both Igh germline transcription and AID expression. By regulating 3' Igk and Igh enhancers and a distal element at the Prdm1 (Blimp1) locus, E-proteins contributed to Igk, Igh, and Prdm1 activation in plasmablasts. Together, these data identified E2A and E2-2 as central regulators of B cell immunity. PMID- 27261531 TI - The effect of metropolitan-area mortgage delinquency on health behaviors, access to health services, and self-rated health in the United States, 2003-2010. AB - The recent housing crisis offers the opportunity to understand the effects of unique indicators of macroeconomic conditions on health. We linked data on the proportion of mortgage borrowers per US metropolitan-area who were at least 90 days delinquent on their payments with individual-level outcomes from a representative sample of 1,021,341 adults surveyed through the Behavioral Risk Factor Surveillance System (BRFSS) between 2003 and 2010. We estimated the effects of metropolitan-area mortgage delinquency on individual health behaviors, medical coverage, and health status, as well as whether effects varied by race/ethnicity. Results showed that increases in the metropolitan-area delinquency rate resulted in decreases in heavy alcohol consumption and increases in exercise and health insurance coverage. However, the delinquency rate was also associated with increases in smoking and obesity in some population groups, suggesting the housing crisis may have induced stress-related behavioral change. Overall, the effects of metropolitan-area mortgage delinquency on population health were relatively modest. PMID- 27261532 TI - Identifying components in consent information needed to support informed decision making about trial participation: An interview study with women managing cancer. AB - BACKGROUND: Research governance requires patients give informed consent to participate in clinical trials. However, there are concerns that consent information may not support patient participation decisions. This study investigates the utility of consent information in supporting women's trial participation decisions when receiving treatment for cancer. DESIGN: An interview study with women receiving cancer treatments at a medical oncology outpatient clinic in Yorkshire (UK). All women over 18 years, not admitted to a hospital ward and who had currently or previously been invited to take part in a trial were invited to take part in the study over a three month period. Interviews were audio-tape recorded, transcribed and analysed using thematic analysis. RESULTS: Of those eligible (n = 41), 21 women with breast (n = 11), ovarian (n = 8) and endometrial (n = 2) cancer participated (mean age = 57 years). Eighteen had made at least one trial decision and three were considering taking part in a trial. Findings are synthesised under two analytical themes: 1) Influence of the cancer and cancer treatment context on decision making for trial participation; and 2) Experiences of the consenting process and their influence on decision making. CONCLUSIONS: Designing trial information to represent explicitly the trial participation decision as being between standard care and study-related care options is more likely to effectively support patients in making informed decisions between standard care treatments and taking part in a trial. PMID- 27261533 TI - Regional inequalities in self-rated health in Russia: What is the role of social and economic capital? AB - Using the data from the European Social Survey (round 6, 2012), this article studies regional inequalities in self-rated health in Russia and examines the role that socio-demographic factors and economic and social capital play in these differences. Also, the regional variation in the determinants of self-rated health is analysed. The article argues that there are considerable and statistically significant unadjusted differences in self-rated health across Russian Federal Districts. We elaborated these differences by regression adjustments, with the result that some of the differences were explained by our predictors and some were amplified. The odds for good self-rated health were lower in the Volga than in Central Russia due to age and socio-economic composition. In contrast, the regression adjustments amplified the differences of the Northwest and the South in comparison to the Central District. The odds for good self-rated health were considerably lower in the Far Eastern part of the country than in the Central District, independently of the adjustments. While social and economic capital predicted good self-rated health at the individual level, they did not explain regional differences. Interaction analyses revealed regional variation in some of the determinants of self-rated health. Most notably, the effects of age, trade union membership and volunteering depended on the regional context. This article argues that the healthcare reforms that transfer funding responsibilities to regional administration may be dangerous for the already less affluent and less healthy rural regions. Thus, regional governance has a growing importance in preventing increases in health inequalities. PMID- 27261534 TI - The social life of the dead: The role of post-mortem examinations in medical student socialisation. AB - Dissection has held a privileged position in medical education although the professional values it inculcates have been subject to intense debate. Claims vary from it generating a dehumanising level of emotional detachment, to promotion of rational and dispassionate decision-making, even to being a positive vehicle for ethical education. Social scientists have positioned dissection as a critical experience in the emotional socialisation of medical students. However, curricular revision has provoked debate about the style and quantity of anatomy teaching thus threatening this 'rite of passage' of medical students. Consequently, some UK medical schools do not employ dissection at all. In its place, observation of post-mortem examinations - a long established, if underutilised, practice - has re-emerged in an attempt to recoup aspects of anatomical knowledge that are arguably lost when dissection is omitted. Bodies for post-mortem examinations and bodies for dissection, however, have striking differences, meaning that post-mortem examinations and dissection cannot be considered comparable opportunities to learn anatomy. In this article, we explore the distinctions between dissection and post-mortem examinations. In particular, we focus on the absence of a discourse of consent, concerns about bodily integrity, how the body's shifting ontology, between object and person, disrupts students' attempts to distance themselves, and how the observation of post-mortem examinations features in the emotional socialisation of medical students. PMID- 27261535 TI - Multimodality imaging for solution of the old dilemma: Pannus or thrombus. PMID- 27261536 TI - Oral butyrate reduces oxidative stress in atherosclerotic lesion sites by a mechanism involving NADPH oxidase down-regulation in endothelial cells. AB - Butyrate is a 4-carbon fatty acid that has antiinflammatory and antioxidative properties. It has been demonstrated that butyrate is able to reduce atherosclerotic development in animal models by reducing inflammatory factors. However, the contribution of its antioxidative effects of butyrate on atherogenesis has not yet been studied. We investigated the influence of butyrate on oxidative status, reactive oxygen species (ROS) release and oxidative enzymes (NADPH oxidase and iNOS) in atherosclerotic lesions of ApoE(-/-) mice and in oxLDL-stimulated peritoneal macrophages and endothelial cells (EA.hy926). The lesion area in aorta was reduced while in the aortic valve, although lesion area was unaltered, superoxide production and protein nitrosylation were reduced in butyrate-supplemented mice. Peritoneal macrophages from the butyrate group presented a lower free radical release after zymosan stimulus. When endothelial cells were pretreated with butyrate before oxLDL stimulus, the CCL-2 and superoxide ion productions and NADPH oxidase subunit p22phox were reduced. In macrophage cultures, in addition to a reduction in ROS release, nitric oxide and iNOS expression were down-regulated. The data suggest that one mechanism related to the effect of butyrate on atherosclerotic development is the reduction of oxidative stress in the lesion site. The reduction of oxidative stress related to NADPH oxidase and iNOS expression levels associated to butyrate supplementation attenuates endothelium dysfunction and macrophage migration and activation in the lesion site. PMID- 27261537 TI - Pharmacogenetics of dabigatran etexilate interindividual variability. AB - INTRODUCTION: Dabigatran etexilate is given in fixed doses without coagulation monitoring for the prevention of blood clots in at risk adults. A high inter individual variability in blood concentrations of the active metabolite of dabigatran has been reported. ABCB1 and CES1 exert an important effect in the metabolism of dabigatran etexilate and allele variants at these two loci are likely to play a pivotal role. To investigate whether screening for polymorphisms within the ABCB1 and the CES1 genes would explain a portion of the inter individual variability in blood concentrations of the active metabolite of dabigatran. MATERIAL AND METHODS: In a cohort of patients who had atrial fibrillation and on anticoagulant prophylaxis with dabigatran etexilate, we investigated whether genotypes at rs4148738 (ABCB1), rs8192935 (CES1), and rs2244613 (CES1) loci would affect plasma dabigatran trough and peak concentrations. RESULTS AND DISCUSSION: Among 92 patients (median age: 72.0years, range: 52-92) analyzed, no clinical variable or genotype was associated with a significant difference in dabigatran peak concentrations. As for trough concentrations, in addition to creatinine clearance, and sex a significant association with the CES1 SNP rs8192935 (p=0.023) was detected. The mean adjusted plasma levels were higher among patients with the CC genotype (86.3ng/dl) than in those carrying the T allele (62.1ng/dl). No significant effect was found for the ABCB1 SNP rs4148738. The CES1 SNP rs8192935 significantly influenced the dabigatran trough concentrations and carriers of the T allele showed significantly lower concentrations than did carriers of the CC genotype. PMID- 27261538 TI - High-dose corticosteroid associated with catheter-related thrombosis after allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are at an increased risk of thrombotic complications, most of which are catheter-related and present a substantial challenge. The incidence of CRT varies considerably depending on clinical factors. However, the underlying pathogenesis and risk factors remain unclear. METHODS: We performed a retrospective nested case-control study in patients following allo-HSCT. Thrombotic episodes were diagnosed based on the clinical suspicion of the physician (pain, swelling, etc.) with subsequent CVC or PICC thrombosis confirmed via duplex ultrasound. Cases with CRT and controls were matched for time of HSCT, age at HSCT, donor source and type of insertion (CVCs or PICC). RESULTS: During the 8-year period, catheters were placed in 2896 patients, with a total of 40 patients (1.38%) developed CRT, among which 11 were associated with CVCs and 29 were associated with PICCs. The median duration from catheter insertion to thrombosis was 97days. Despite reports of an association between thrombosis and infection, central line-associated bloodstream infection was comparable between groups. No significant differences were noted in terms of primary disease, donor type, conditioning regimen or catheter type between the cases and controls. A multivariate regression analysis identified high-dose corticosteroids as independent risk factors for the development of CRT. CRT seems to negatively affect prognosis in allo-HSCT patients. CONCLUSION: In conclusion, we demonstrate that the use of high-dose corticosteroids is correlated with the onset of CRT. However, the efficacy and safety of thromboprophylaxis in this population require further investigation. PMID- 27261539 TI - Do people reason rationally about causally related events? Markov violations, weak inferences, and failures of explaining away. AB - Making judgments by relying on beliefs about the causal relationships between events is a fundamental capacity of everyday cognition. In the last decade, Causal Bayesian Networks have been proposed as a framework for modeling causal reasoning. Two experiments were conducted to provide comprehensive data sets with which to evaluate a variety of different types of judgments in comparison to the standard Bayesian networks calculations. Participants were introduced to a fictional system of three events and observed a set of learning trials that instantiated the multivariate distribution relating the three variables. We tested inferences on chains X1->Y->X2, common cause structures X1<-Y->X2, and common effect structures X1->Y<-X2, on binary and numerical variables, and with high and intermediate causal strengths. We tested transitive inferences, inferences when one variable is irrelevant because it is blocked by an intervening variable (Markov Assumption), inferences from two variables to a middle variable, and inferences about the presence of one cause when the alternative cause was known to have occurred (the normative "explaining away" pattern). Compared to the normative account, in general, when the judgments should change, they change in the normative direction. However, we also discuss a few persistent violations of the standard normative model. In addition, we evaluate the relative success of 12 theoretical explanations for these deviations. PMID- 27261540 TI - Effects of rhythm on memory for spoken sequences: A model and tests of its stimulus-driven mechanism. AB - Immediate memory for spoken sequences depends on their rhythm - different levels of accuracy and patterns of error are seen according to the way in which items are spaced in time. Current models address these phenomena only partially or not at all. We investigate the idea that temporal grouping effects are an emergent property of a general serial ordering mechanism based on a population of oscillators locally-sensitive to amplitude modulations on different temporal scales. Two experiments show that the effects of temporal grouping are independent of the predictability of the grouping pattern, consistent with this model's stimulus-driven mechanism and inconsistent with alternative accounts in terms of top-down processes. The second experiment reports detailed and systematic differences in the recall of irregularly grouped sequences that are broadly consistent with predictions of the new model. We suggest that the bottom up multi-scale population oscillator (or BUMP) mechanism is a useful starting point for a general account of serial order in language processing more widely. PMID- 27261542 TI - From Bench to Bedside: Understanding Stress-Obesity Research Within the Context of Translation to Improve Pediatric Behavioral Weight Management. AB - A growing body of literature suggests that stress, including chronic stress and acute physiologic stress reactivity, is one contributor to the development and maintenance of obesity in youth. Little has been done to apply the literature on stress and obesity risk to inform the development of pediatric behavioral weight control (BWC) interventions. The aims of this review are to (1) discuss research linking stress and pediatric obesity, (2) provide examples of the implications of the stress-obesity research for pediatric BWC development, and (3) propose that a mindfulness-based approach may be useful in targeting stress reduction within pediatric BWC. PMID- 27261541 TI - National Institutes of Health Update: Translating Basic Behavioral Science into New Pediatric Obesity Interventions. AB - Pediatric obesity increases the risk of later-life obesity and chronic diseases. Basic research to better understand factors associated with excessive weight gain in early life and studies translating research findings into preventive and therapeutic strategies are essential to our ability to better prevent and treat childhood obesity. This overview describes several National Institutes of Health efforts designed to stimulate basic and translational research in childhood obesity prevention and treatment. These examples demonstrate the value of research in early phase translational pediatric obesity research and highlight some promising directions for this important area of research. PMID- 27261543 TI - Behavioral Economic Factors Related to Pediatric Obesity. AB - Behavioral economics (BE) suggests that food and activity choices are governed by costs, available alternatives, and reinforcement. This article reviews basic, translational, and intervention research using a BE framework with overweight or obese children up to age 18. We address BE concepts and methods, and discuss developmental issues, the continuum of BE intervention approaches, findings of studies focused on increasing the cost of unwanted behaviors (ie, energy-dense food intake and sedentary behavior) and decreasing the cost of desired behaviors (ie, healthy food intake and PA), and our team's recent basic behavioral studies using BE approaches with minority adolescents. PMID- 27261544 TI - Neurocognitive Processes and Pediatric Obesity Interventions: Review of Current Literature and Suggested Future Directions. AB - Childhood obesity is a significant problem in the United States, but current childhood obesity prevention approaches have limited efficacy. Self-regulation processes organize behavior to achieve a goal and may shape health behaviors and health outcomes. Obesity prevention approaches that focus on the cognitive and behavioral mechanisms that underlie self-regulation early in life may therefore lead to better outcomes. This article reviews the development of executive functioning (EF), identifies influences on EF development, discusses aspects of EF relating to increased risk for childhood obesity, and considers how EF-weight associations may change across development. Implications for intervention are discussed. PMID- 27261545 TI - Physical Activity Interventions for Neurocognitive and Academic Performance in Overweight and Obese Youth: A Systematic Review. AB - This article examines cognitive, academic, and brain outcomes of physical activity in overweight or obese youth, with attention to minority youth who experience health disparities. Physically active academic lessons may have greater immediate cognitive and academic benefits among overweight and obese children than normal-weight children. Quasi-experimental studies testing physical activity programs in overweight and obese youth show promise; a few randomized controlled trials including African Americans show efficacy. Thus, making academic lessons physically active may improve inhibition and attentiveness, particularly in overweight youngsters. Regular physical activity may be efficacious for improving neurologic, cognitive, and achievement outcomes in overweight or obese youth. PMID- 27261547 TI - Development of a Behavioral Sleep Intervention as a Novel Approach for Pediatric Obesity in School-aged Children. AB - Despite being the focus of widespread public health efforts, childhood obesity remains an epidemic worldwide. Given the now well-documented consequences of obesity for childhood health and psychosocial functioning, as well as associated morbidity in adulthood, identifying novel, modifiable behaviors that can be targeted to improve weight control is imperative. Enhancing children's sleep may show promise in assisting with weight regulation. The present paper describes the development of a brief behavioral sleep intervention for school-aged children, including preliminary findings of this work as well as areas for future study. PMID- 27261546 TI - Treating Obesity in Preschoolers: A Review and Recommendations for Addressing Critical Gaps. AB - Developing interventions targeting obesity reduction in preschoolers is an emergent area. Although intensive, multicomponent interventions seem a promising approach to preschool obesity reduction, this review identifies and discusses approaches to 3 critical gaps (poor reach to families from low-income and minority backgrounds, lack of sufficient evidence to determine the most effective and efficient treatment components and approaches to treating obesity in early childhood, and lack of consensus on how best to discern intervention effectiveness) that need to be addressed to advance the preschool obesity literature. PMID- 27261548 TI - Effective Patient-Provider Communication in Pediatric Obesity. AB - Effective patient-provider communication is not a primary focus of medical school curricula. Motivational interviewing (MI) is a patient-centered, directive communication framework appropriate for in health care. Research on MI's causal mechanisms has established patient change talk as a mediator of behavior change. Current MI research focuses on identifying which provider communication skills are responsible for evoking change talk. MI recommends informing, asking, and listening. Research provides evidence that asking for and reflecting patient change talk are effective communication strategies, but cautions providers to inform judiciously. Supporting a patient's decision making autonomy is an important strategy to promote health behaviors. PMID- 27261549 TI - Advances in Motivational Interviewing for Pediatric Obesity: Results of the Brief Motivational Interviewing to Reduce Body Mass Index Trial and Future Directions. AB - Rates of childhood obesity in the United States remain at historic highs. The pediatric primary care office represents an important yet underused setting to intervene with families. One factor contributing to underuse of the primary care setting is lack of effective available interventions. One evidence-based method to help engage and motivate patients is motivational interviewing, a client centered and goal-oriented style of counseling used extensively to increase autonomous motivation and modify health behaviors. This article summarizes the methods and results from a large trial implemented in primary care pediatric office and concludes with recommendations for improving the intervention and increasing its dissemination. PMID- 27261550 TI - New Directions in Behavioral Intervention Development for Pediatric Obesity. PMID- 27261551 TI - From Bench to Bedside: T1 Translation of Basic Behavioral Science into Novel Pediatric Obesity Interventions. PMID- 27261552 TI - Errata. PMID- 27261553 TI - Development of sleep/wake, activity and temperature rhythms in newborns maintained in a neonatal intensive care unit and the impact of feeding schedules. AB - Biological rhythms in infants are described as evolving from an ultradian to a circadian pattern along the first months of life. Recently, the use of actigraphy and thermistors with memory has contributed to the understanding of temporal relations of different variables along development. The aim of this study was to describe and compare the development of the rhythmic pattern of wrist temperature, activity/rest cycle, sleep/wake and feeding behavior in term and preterm newborns maintained in a neonatal intensive care unit (NICU). METHODS: Nineteen healthy preterm and seven fullterm newborns had the following variables monitored continuously while they were in the NICU: activity recorded by actigraphy, wrist temperature recorded with a thermistor and observed sleep and feeding behavior recorded by the NICU staff with diaries. Subjects were divided in 3 groups according to their gestational age at birth and rhythmic parameters were compared. RESULTS: A dominant daily rhythm was observed for wrist temperature since the first two weeks of life and no age relation was demonstrated. Otherwise, a daily pattern in activity/rest cycle was observed for most preterm newborns since 35 weeks of postconceptional age and was more robust in term babies. Feeding and sleep/wake data showed an almost exclusive 3h rhythm, probably related to a masking effect of feeding schedules. CONCLUSIONS: We found that wrist temperature develops a daily pattern as soon as previously reported for rectal temperature, and with acrophase profile similar to adults. Moreover, we were able to find a daily rhythm in activity/rest cycle earlier than previously reported in literature. We also suggest that sleep/wake rhythm and feeding behavior follow independent developmental courses, being more suitable to masking effects. PMID- 27261555 TI - The influence of pedestrian countdown signals on children's crossing behavior at school intersections. AB - Previous studies have shown that pedestrian countdown signals had different influences on pedestrian crossing behavior. The purpose of this study was to examine the effects of the installation of countdown signals at school intersections on children's crossing behavior. A comparison analysis was carried out on the basis of observations at two different school intersections with or without pedestrian countdown signals in the city of Jinan, China. Four types of children's crossing behavior and child pedestrian-vehicle conflicts were analyzed in detail. The analysis results showed that using pedestrian countdown timers during the Red Man phase led to more children's violation and running behavior. Theses violators created more conflicts with vehicles. However, pedestrian countdown signals were effective at helping child pedestrian to complete crossing before the red light onset, avoid getting caught in the middle of crosswalk. No significant difference was found in children who started crossing during Flashing Green Man phase between the two types of pedestrian signals. Moreover, analysis results indicated that children who crossed the road alone had more violation and adventure crossing behavior than those had companions. Boys were found more likely to run crossing than girls, but there was no significant gender difference in other crossing behavior. Finally, it's recommended to remove countdown at the end of the Red Man phase to improve children's crossing behavior and reduce the conflicts with vehicles. Meanwhile other measures are proposed to improve children safety at school intersections. PMID- 27261554 TI - Determinants of road traffic safety: New evidence from Australia using state space analysis. AB - This paper examines the determinants of road traffic crash fatalities in Queensland for the period 1958-2007 using a state-space time-series model. In particular, we investigate the effects of policies that aimed to reduce drink driving on traffic fatalities, as well as indicators of the economic environment that may affect exposure to traffic, and hence affect the number of accidents and fatalities. The results show that the introduction of a random breath testing program in 1988 was associated with a 11.3% reduction in traffic fatalities; its expansion in 1998 was associated with a 26.2% reduction in traffic fatalities; and the effect of the "Safe4life" program, which was introduced in 2004, was a 14.3% reduction in traffic fatalities. Reductions in economic activity are also associated with reductions in road fatalities: we estimate that a one percent increase in the unemployment rate is associated with a 0.2% reduction in traffic fatalities. PMID- 27261556 TI - Less is better in geriatrics. PMID- 27261557 TI - A meta-analysis synthesizing the effects of pesticides on swim speed and activity of aquatic vertebrates. AB - Pesticide contaminants are ubiquitous in aquatic environments and pose a threat to biodiversity. Pesticides also have diverse mechanisms of action that make it difficult to identify impacts on exposed wildlife. Behavioral measures represent an important link between physiological and ecological processes, and are often used to generalize sub-lethal effects of pesticide exposure. In order to bridge the toxicological and behavioral literature, and identify chemical classes that denote the largest threat, we conducted a meta-analysis summarizing the effects of pesticides on swim speed and activity of aquatic vertebrates. We found that exposure to environmentally relevant concentrations of pesticides reduced the swim speed of exposed amphibians and fish by 35%, and reduced overall activity by 72%. There were also differences in the magnitude of this effect across chemical classes, which likely reflect underlying physiological processes. Pyrethroids, carbamates, and organophosphates all produced a large decrease in swim speed, where as phosphonoglycines and triazines showed no overall effect. Pyrethroids, carbamates, organophosphates, organochlorines, and organotins also produced a large decrease in activity, while phosphonoglycines had no overall effect, and triazines had the opposite effect of increasing activity. Our results indicate that even sub-lethal concentrations of pesticides have a strong effect on critical behaviors of aquatic vertebrates, which can affect fitness and alter species interactions. We expect our synthesis can be used to identify chemical classes producing the largest sub-lethal effects for further research and management. PMID- 27261558 TI - Resokaempferol-mediated anti-inflammatory effects on activated macrophages via the inhibition of JAK2/STAT3, NF-kappaB and JNK/p38 MAPK signaling pathways. AB - The excessive or prolonged production of inflammatory mediators can result in numerous chronic diseases, such as rheumatoid arthritis, atherosclerosis, diabetes, and cancer. Therefore, for many inflammatory-related diseases, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators. Novel therapeutics and mechanistic insight are sought for the management of chronic inflammatory diseases. Resokaempferol (RES) is a type of flavonoid recently reported to demonstrate anti-cancer properties. However, the anti-inflammatory capacity of RES has not been studied to date. Therefore, this study investigated whether RES is capable of suppressing the inflammatory response to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the mechanism by which this is achieved. We found that RES attenuated the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1) and IL 6. RES also inhibited the nuclear translocation of signal transducer and activator of transcription (STAT) 3 and reduced the LPS-mediated phosphorylation of Janus kinase (JAK) 2 and STAT3 at the sites of Ser727 and Tyr705. RES also inhibited the activation of NF-kappaB and JNK/p38 MAPK signaling pathways in LPS induced RAW264.7 cells. Additionally, RES inhibited the activation of the JAK2/STAT3 pathway in exogenous IL-6-activated RAW264.7 macrophages. We conclude that RES inhibits the inflammatory response in activated macrophages by blocking the activation of the JAK2/STAT3 pathway by both LPS and IL-6 signaling. PMID- 27261559 TI - Rate of increase of lung-to-head ratio over the course of gestation is predictive of survival in left-sided congenital diaphragmatic hernia. AB - PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with high postnatal mortality because of pulmonary hypoplasia. The prognostic utility of serial lung to-head circumference measurements as a marker of lung growth has not been described. Our objective was to examine the relationship between the rate of interval increase of LHR and postnatal survival in left-sided CDH. METHODS: We retrospectively reviewed charts of all left-sided CDH patients from January 2004 to July 2014. All ultrasound studies performed at our institution (n=473) were reviewed. Categorical and continuous data were analyzed by chi-square and Mann Whitney t-test, respectively, and slope analysis was performed by linear regression analysis (p<0.05). RESULTS: A total of 226 patients were studied, with 154 long-term survivors and 72 non-survivors. Established markers of CDH severity, including intrathoracic liver position and requirement for patch repair, were significantly increased in non-survivors (p<0.0001). The rate of LHR increase as measured by linear regression and slope analysis was significantly increased in long-term survivors (p=0.0175). CONCLUSIONS: Our findings indicate that the interval increase in LHR levels over the course of gestation correlate with survival in left-sided CDH patients. Regular ultrasonographic re-evaluation of LHR throughout gestation following diagnosis of CDH may provide prognostic insight and help guide patient management. PMID- 27261560 TI - The treatment of abdominoscrotal hydrocele: Is there a role for nonoperative management? AB - BACKGROUND/PURPOSE: Abdominoscrotal hydrocele (ASH) is an uncommon entity. Until now, the recommended treatment has been surgical. There is only one successful case of nonoperative management reported in literature. We report the largest series of children with ASH, and provide evidence in support of an initial nonoperative approach. METHODS: This study is a retrospective chart review of patients treated from 1994 to 2015 with ASH at a single institution. RESULTS: Thirty patients were identified with ASH, with 29 included in the analysis. Nine patients (30%) had operative management with an 80% complication rate. Twenty out of 29 patients (70%) were initially managed expectantly. Sixteen (80%) had resolution of their abdominal component, twelve (60%) of which went on to have full resolution of ASH. Four patients (20%) in this group required operative management of ASH. CONCLUSIONS: ASH should be included in the differential diagnosis of pediatric scrotal swelling. The "Springing Back Ball Sign" should be used as a screening tool. If it is positive, a dynamic ultrasound should be performed to confirm the diagnosis. We recommend observation as the first step in the management of uncomplicated ASH. It can result in avoidance of operation or at least lower the complication risk significantly if operation is required. LEVEL OF EVIDENCE: 4. PMID- 27261561 TI - Timing of bariatric surgery for severely obese adolescents: a Markov decision analysis. AB - PURPOSE: Although controversial, bariatric surgery is increasingly being performed in adolescents. We developed a model to simulate the effect of timing of gastric bypass in obese adolescents on quantity and quality of life. METHODS: A Markov state-transition model was constructed comparing two treatment strategies: gastric bypass surgery at age 16 versus delayed surgery in adulthood. The model simulated a hypothetical cohort of adolescents with body mass index of 45kg/m(2). Model inputs were derived from current literature. The main outcome measure was quality and quantity of life, measured using quality-adjusted life years (QALYs). RESULTS: For females, early gastric bypass surgery was favored by 2.02 QALYs compared to delaying surgery until age 35 (48.91 vs. 46.89 QALYs). The benefit was even greater for males, where early surgery was favored by 2.9 QALYs (48.30 vs. 45.40 QALYs). The absolute benefit of surgery at age 16 increased; the later surgery was delayed into adulthood. Sensitivity analyses demonstrated that adult surgery was favored only when the values for adverse events were unrealistically high. CONCLUSIONS: In our model, early gastric bypass in obese adolescents improved both quality and quantity of life. These findings are useful for surgeons and pediatricians when counseling adolescents considering weight loss surgery. PMID- 27261562 TI - Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for Social Anxiety Disorder and comorbid disorders: A randomized controlled trial. AB - Disorder-specific (DS-CBT) and transdiagnostic (TD-CBT) cognitive behaviour therapy have both been used to treat social anxiety disorder (SAD). This study compared internet-delivered DS-CBT and TD-CBT for SAD across clinician-guided (CG CBT) and self-guided (SG-CBT) formats. Participants with SAD (n=233) were randomly allocated to receive internet-delivered TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of SAD (Cohen's d>=1.01; avg. reduction>=30%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen's d>=1.25; avg. reduction>=39%), generalised anxiety disorder (Cohen's d>=0.86; avg. reduction>=36%) and panic disorder (Cohen's d>=0.53; avg. reduction>=25%) were found immediately post-treatment and were maintained or further improved to 24-month follow-up. No marked differences were observed between TD-CBT and DS-CBT or CG-CBT and SG-CBT highlighting the potential of each for the treatment of SAD and comorbid disorders. PMID- 27261563 TI - Attention deficit hyperactivity disorder medications in children with heart disease. AB - PURPOSE OF REVIEW: Attention deficit hyperactivity disorder (ADHD) is quite common in the general pediatric population, Its incidence is thought to be even higher in the population of patients with congenital heart disease, especially in those patients with complex disease and who have had cardiac surgical interventions early in life. There has been controversy as to the safety of ADHD medications, especially in the latter population of patients. This compendium is meant to review the effects of the ADHD medications and the safety of these medications in patients with either known or undiagnosed congenital heart disease. RECENT FINDINGS: The concern with regard to the use of ADHD medications has been as a result of the reports of sudden unexpected deaths among patients taking stimulant drugs for ADHD. Therefore, the question of whether or not stimulant drugs increase the risk of adverse cardiovascular events has led to a discussion of the appropriate use of these drugs in patients with known cardiovascular disease, as well as a discussion as to the appropriate evaluation in order to identify undiagnosed 'at-risk' patients with congenital heart disease or arrhythmias. This article will review and amplify these discussions, as well as the conclusions that have come forth as a result of these discussions. SUMMARY: Currently available data suggest that there is no evidence for serious adverse cardiovascular complications in children with known cardiovascular diseases including patients of congenital heart disease who are treated with stimulant medications. Despite this, if the patient does have known cardiac disease, or if the history and physical examination is suggestive of cardiac disease, it is suggested that consultation/evaluation with a pediatric cardiologist occur. It is extremely unlikely that stimulant medications would be contraindicated in almost any condition that falls under this category. However, a few specific cardiac conditions might tailor the choice of the specific ADHD medication. Therefore the coordination of care between the primary care physician, the ADHD medication-prescribing physician, and the pediatric cardiologist may be very important in this circumstance. PMID- 27261564 TI - White matter integrity in major depressive disorder: Implications of childhood trauma, 5-HTTLPR and BDNF polymorphisms. AB - This study examined the impact of childhood neglect, serotonin transporter (5 HTTLPR) and brain derived neurotrophic factor (BDNF) polymorphisms on white matter (WM) integrity in major depressive disorder (MDD) using diffusion tensor imaging (DTI). Fifty-five medication-free MDD patients and 18 controls underwent diffusion tensor imaging scanning, genotyping and completed the Childhood Trauma Questionnaire. Tract based spatial statistics (TBSS) findings revealed reduced fractional anisotropy (FA) in the MDD group in the anterior internal capsule. 5 HTTLPR-S'L' heterozygotes in the MDD group exhibited reduced FA in the internal capsule relative to S'S' and reduced FA in corona radiata compared to L'L'. Probabilistic tractography revealed higher FA in the uncinate fasciculus (UF) for BDNF val/val genotype relative to met-carriers, particularly in individuals with high depression severity. High depression severity and experiences of childhood physical or emotional neglect predicted higher FA in the UF and superior longitudinal fasciculus. Reductions in FA were identified for subgroups of MDD patients who were 5-HTTLPR heterozygotes and BDNF-met carriers. An association between emotional/physical neglect and FA was observed in subjects with high depressive symptoms. Our findings suggest that WM connectivity within frontal and limbic regions are affected by depression and influenced by experiences of neglect and genetic risk factors. PMID- 27261565 TI - Automated development of artificial neural networks for clinical purposes: Application for predicting the outcome of choledocholithiasis surgery. AB - Among various expert systems (ES), Artificial Neural Network (ANN) has shown to be suitable for the diagnosis of concurrent common bile duct stones (CBDS) in patients undergoing elective cholecystectomy. However, their application in practice remains limited since the development of ANNs represents a slow process that requires additional expertize from potential users. The aim of this study was to propose an ES for automated development of ANNs and validate its performances on the problem of prediction of CBDS. Automated development of the ANN was achieved by applying the evolutionary assembling approach, which assumes optimal configuring of the ANN parameters by using Genetic algorithm. Automated selection of optimal features for the ANN training was performed using a Backward sequential feature selection algorithm. The assessment of the developed ANN included the evaluation of predictive ability and clinical utility. For these purposes, we collected data from 303 patients who underwent surgery in the period from 2008 to 2014. The results showed that the total bilirubin, alanine aminotransferase, common bile duct diameter, number of stones, size of the smallest calculus, biliary colic, acute cholecystitis and pancreatitis had the best prognostic value of CBDS. Compared to the alternative approaches, the ANN obtained by the proposed ES had better sensitivity and clinical utility, which are considered to be the most important for the particular problem. Besides the fact that it enabled the development of ANNs with better performances, the proposed ES significantly reduced the complexity of ANNs' development compared to previous studies that required manual selection of optimal features and/or ANN configuration. Therefore, it is concluded that the proposed ES represents a robust and user-friendly framework that, apart from the prediction of CBDS, could advance and simplify the application of ANNs for solving a wider range of problems. PMID- 27261566 TI - Electrocatalytic processes promoted by diamond nanoparticles in enzymatic biosensing devices. AB - We have developed a biosensing platform for lactate determination based on gold electrodes modified with diamond nanoparticles of 4nm of nominal diameter, employing the enzyme lactate oxidase and (hydroxymethyl)ferrocene (HMF) as redox mediator in solution. This system displays a response towards lactate that is completely different to those typically observed for lactate biosensors based on other nanomaterials, such as graphene, carbon nanotubes, gold nanoparticles or even diamond nanoparticles of greater size. We have observed by cyclic voltammetry that, under certain experimental conditions, an irreversible wave (E(0)=+0.15V) appears concomitantly with the typical Fe(II)/Fe(III) peaks (E(0)=+0.30V) of HMF. In this case, the biosensor response to lactate shows simultaneous electrocatalytic peaks at +0.15V and +0.30V, indicating the concurrence of different feedback mechanisms. The achievement of a biosensor response to lactate at +0.15V is very convenient in order to avoid potential interferences. The developed biosensor presents a linear concentration range from 0.02mM to 1.2mM, a sensitivity of 6.1MUAmM(-1), a detection limit of 5.3MUM and excellent stability. These analytical properties compare well with those obtained for other lactate-based biosensors that also include nanomaterials and employ HMF as redox mediator. PMID- 27261567 TI - Investigation of polymer-shelled microbubble motions in acoustophoresis. AB - The objective of this paper is to explore the trajectory motion of microsize (typically smaller than a red blood cell) encapsulated polymer-shelled gas bubbles propelled by radiation force in an acoustic standing-wave field and to compare the corresponding movements of solid polymer microbeads. The experimental setup consists of a microfluidic chip coupled to a piezoelectric crystal (PZT) with a resonance frequency of about 2.8MHz. The microfluidic channel consists of a rectangular chamber with a width, w, corresponding to one wavelength of the ultrasound standing wave. It creates one full wave ultrasound of a standing-wave pattern with two pressure nodes at w/4 and 3w/4 and three antinodes at 0, w/2, and w. The peak-to-peak amplitude of the electrical potential over the PZT was varied between 1 and 10V. The study is limited to no-flow condition. From Gor'kov's potential equation, the acoustic contrast factor, Phi, for the polymer shelled microbubbles was calculated to about -60.7. Experimental results demonstrate that the polymer-shelled microbubbles are translated and accumulated at the pressure antinode planes. This trajectory motion of polymer-shelled microbubbles toward the pressure antinode plane is similar to what has been described for other acoustic contrast particles with a negative Phi. First, primary radiation forces dragged the polymer-shelled microbubbles into proximity with each other at the pressure antinode planes. Then, primary and secondary radiation forces caused them to quickly aggregate at different spots along the channel. The relocation time for polymer-shelled microbubbles was 40 times shorter than that for polymer microbeads, and in contrast to polymer microbeads, the polymer-shelled microbubbles were actuated even at driving voltages (proportional to radiation forces) as low as 1V. In short, the polymer-shelled microbubbles demonstrate the behavior attributed to the negative acoustic contrast factor particles and thus can be trapped at the antinode plane and thereby separated from particles having a positive acoustic contrast factor, such as for example solid particles and cells. This phenomenon could be utilized in exploring future applications, such as bioassay, bioaffinity, and cell interaction studies in vitro in a well-controlled environment. PMID- 27261568 TI - The Risk of Cancer With the Use of Recombinant Human Bone Morphogenetic Protein in Spine Fusion. AB - STUDY DESIGN: Retrospective cohort study using the Washington State Comprehensive Hospital Abstract Reporting System, the Washington State Cancer Registry, and Washington State death certificates. OBJECTIVE: To study the possible association between recombinant human bone morphogenetic protein (rhBMP) and cancer risk. SUMMARY OF BACKGROUND DATA: The use of rhBMP in spine fusion surgery remains controversial with respect to its possible role in tumorigenesis. METHODS: We compared adults who underwent spine fusion for degenerative disease with and without rhBMP between 2002 and 2010. Patients were matched on the basis of age, sex, and year of treatment. We excluded patients with a diagnosis of cancer before or at the index procedure. The primary outcome was the first diagnosis of cancer as identified in the records of the cancer registry. RESULTS: We included 16,914 patients who had spine fusion, of whom 4246 received rhBMP. During the study period, 449 patients received a diagnosis of cancer: 117 (2.76% of 4246) in the rhBMP group and 332 (2.62% of 12 668) in the no rhBMP group. The incidence rate was similar between the rhBMP and no rhBMP 9.5 and 9.0 per 1000 person years, respectively (hazard ratio, 1.06; 95% confidence interval, 0.86-1.30). There were no differences in the rate of cancer between the two groups in subgroups defined on the basis of site of fusion or surgical method. CONCLUSION: There was no increase in overall cancer incidence among those receiving rhBMP. An important limitation of this and other studies of rhBMP and cancer that have been conducted to date is their relatively limited duration of follow-up. The examination of cancer incidence following rhBMP administration must continue beyond just the first several years to adequately assess the potential of rhBMP to influence the occurrence of one or more types of malignancy. LEVEL OF EVIDENCE: 3. PMID- 27261569 TI - MRI-compatible bone phantom for evaluating ultrasonic thermal exposures. AB - OBJECTIVE: The goal of the proposed study was the development of a magnetic resonance imaging (MRI) compatible bone phantom suitable for evaluating focused ultrasound protocols. MATERIALS AND METHODS: High resolution CT images were used to segment femur bone. The segmented model was manufactured with (Acrylonitrile Butadiene Styrene) ABS plastic using a 3-D printer. The surrounding skeletal muscle tissue was mimicked using an agar-silica-evaporated milk gel (2% w/v-2% w/v-40% v/v). MR thermometry was used to evaluate the exposures of the bone phantom to focused ultrasound. RESULTS: The estimated agar-silica-evaporated milk gel's T1 and T2 relaxation times in a 1.5T magnetic field were 776ms and 66ms respectively. MR thermometry maps indicated increased temperature adjacent to the bone, which was also shown in situations of real bone/tissue interfaces. CONCLUSION: Due to growing interest of using MRI guided Focused Ultrasound Surgery (MRgFUS) in palliating bone cancer patients at terminal stages of the disease, the proposed bone phantom can be utilized as a very useful tool for evaluating ultrasonic protocols, thus minimizing the need for animal models. The estimated temperature measured and its distribution near the bone phantom/agar interface which was similar to temperatures recorded in real bone ablation with FUS, confirmed the phantom's functionality. PMID- 27261570 TI - PEBP4 silencing inhibits hypoxia-induced epithelial-to-mesenchymal transition in prostate cancer cells. AB - Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP family and has been reported to be upregulated in various cancer types. The definite function of PEBP4 in regulating the EMT of prostate cancer, however, is still unclear. Here, we examined the functional role of PEBP4 and the underlying molecular mechanisms in hypoxia-induced EMT in prostate cancer cells. Our results showed that PEBP4 mRNA and protein expression was markedly increased in the human prostate cancer tissues and cell lines. Knockdown of PEBP4 significantly inhibited hypoxia-induced migration/invasion and EMT program. Furthermore, knockdown of PEBP4 prevented hypoxia-induced the expression of p-Akt and p-mTOR in prostate cancer cells. Taken together, this study reported here provided evidence that knockdown of PEBP4 inhibited hypoxia-induced EMT in prostate cancer cells. Our study uncovered a novel role for PEBP4 in prostate cancer progression, which might support the potential for PEBP4 targeting in prostate cancer therapy. PMID- 27261571 TI - Cordycepin protects PC12 cells against 6-hydroxydopamine induced neurotoxicity via its antioxidant properties. AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by degeneration and loss of dopaminergic neurons of the substantia nigra. Increasing evidence has indicated that oxidative stress plays a pivotal role in the pathogenesis of Parkinson's disease (PD). Therapeutic options that target the antioxidant machinery may have potential in the treatment of PD. Cordycepin, a nucleoside isolated from Cordyceps species displayed potent antioxidant, anti-inflammatory and anticancer properties. However, its neuroprotective effect against 6-OHDA neurotoxicity as well as underlying mechanisms is still unclear. In this present study, we investigated the protective effect of cordycepin against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its underlying mechanism. We observed that cordycepin effectively inhibited 6-OHDA-induced cell death, apoptosis and mitochondrial dysfunction. Cordycepin also inhibited cell apoptosis induced by 6-OHDA as observed in the reduction of cytochrome c release from the mitochondrial as well as the inhibition of caspase-3. In addition cordycepin markedly reduced cellular malondialdehyde (MDA) content and intracellular reactive oxygen species (ROS) level. Cordycepin also significantly increased the antioxidant enzymes; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in 6 OHDA-treated cells. The results obtained unambiguously demonstrated that cordycepin protects PC12 cells against 6-OHDA-induced neurotoxicity through its potent antioxidant activity. PMID- 27261572 TI - Procyanidins, from Castanea mollissima Bl. shell, induces autophagy following apoptosis associated with PI3K/AKT/mTOR inhibition in HepG2 cells. AB - Procyanidins from Castanea mollissima Bl. shell (CSPCs) induced autophagy and apoptosis in HepG2 cells and its mechanism remains to be examined. In this paper, autophagy was measured by the lipid modification of light chain-3 (LC3) and the formation of autophagosomes. Hoechst 33258 staining and flow cytometer analysis were used to measure apoptosis. The western blot analysis was used to examine the effects of CSPCs on the expression of LC3, PI3K, phosphorylation of AKT, mTOR, Bcl-2, Bad, Bax, BID and cleaved caspase 3 in HepG2 cells. The results showed that 3-methyladenine (3-MA) and apoptosis inhibitor (Z-VAD) could inhibited the death of HepG2 induced by CSPCs for 48h (150MUg/mL). CSPCs induced the accumulation of autophagosomes and microtubule-associated proteins light chain 3 II (LC3-II, a marker of autophagy). P-AKT, PI3K and mTOR were significantly decreased on CSPCs exposure. However, these phenomena were not observed in the group pretreated with the autophagy inhibitor 3-MA and Z-VAD. CSPCs also induced the expression of Bad, Bax and Beclin-1 proteins and decreased the expression of Bcl-2, which was inhibited by 3-MA and Z-VAD. Moreover the apoptotic cell death could be inhibited by 3-MA. In addition, inhibition of LC3-II by siRNA-dependent knockdown attenuated the cleavage of caspase 3. These results suggested CSPCs could trigger autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway, enhanced apoptosis in HepG2 cells which may be associated with the mitochondria dependent signaling way. PMID- 27261573 TI - miR-1301 promotes prostate cancer proliferation through directly targeting PPP2R2C. AB - Prostate cancer is the leading cause of cancer deaths among men in the worldwide, it's important to find new prognostic factors and therapeutic targets. microRNAs play critical roles in the development and progression of prostate cancer. Here we revealed miR-1301 promoted prostate cancer progression. miR-1301 was upregulated in prostate cancer tissues and cells, overexpression of miR-1301 promoted anchorage-dependent and -independent growth using MTT analysis, colony formation analysis and soft agar growth analysis, whereas knockdown of miR-1301 suppressed anchorage-dependent and -independent growth. We also found overexpression of miR-1301 inhibited p27 expression and promoted Cyclin D1 expression, whereas knockdown of miR-1301 reduced this effect, suggesting miR 1301 promoted the G1/S transition. These results suggested miR-1301 promoted cell proliferation of prostate cancer. microRNAs can inhibit target mRNA translation or/and induce mRNA degradation, we found tumor suppresser PPP2R2C was the target of miR-1301, simultaneous downregualtion of PPP2R2C and miR-1301 promoted anchorage-dependent and -independent growth. These findings suggested miR-1301 promoted prostate cancer proliferation by inhibiting PPP2R2C, and might a therapeutic target for prostate cancer. PMID- 27261574 TI - Curcumin and Ellagic acid synergistically induce ROS generation, DNA damage, p53 accumulation and apoptosis in HeLa cervical carcinoma cells. AB - Cervical cancer and precancerous lesions of the cervix continue to be a global health issue, and the medication for the treatment for chronic HPV infection so far has not been effective. Potential anticancer and anti HPV activities of two known phytochemicals, Curcumin and Ellagic acid were evaluated in HeLa cervical cancer cells. Curcumin is a natural compound found in the root of Curcuma longa plant and Ellagic acid a polyphenol found in fruits of strawberries, raspberries and walnuts. The combination of Curcumin and Ellagic acid at various concentrations showed better anticancer properties than either of the drug when used alone as evidenced by MTT assay. Besides this, Curcumin and Ellagic acid also restore p53, induce ROS formation and DNA damage. Mechanistic study further indicated that Curcumin and Ellagic acid show anti-HPV activity as evidenced by decrease in the HPV E6 oncoprotein on HeLa cells. PMID- 27261575 TI - Drug membrane transporters and CYP3A4 are affected by hypericin, hyperforin or aristoforin in colon adenocarcinoma cells. AB - Our previous results have shown that the combination of hypericin-mediated photodynamic therapy (HY-PDT) at sub-optimal dose with hyperforin (HP) (compounds of Hypericum sp.), or its stable derivative aristoforin (AR) stimulates generation of reactive oxygen species (ROS) leading to antitumour activity. This enhanced oxidative stress evoked the need for an explanation for HY accumulation in colon cancer cells pretreated with HP or AR. Generally, the therapeutic efficacy of chemotherapeutics is limited by drug resistance related to the overexpression of drug efflux transporters in tumour cells. Therefore, the impact of non-activated hypericin (HY), HY-PDT, HP and AR on cell membrane transporter systems (Multidrug resistance-associated protein 1-MRP1/ABCC1, Multidrug resistance-associated protein 2-MRP2/ABCC2, Breast cancer resistance protein - BCRP/ABCG2, P-glycoprotein-P-gp/ABCC1) and cytochrome P450 3A4 (CYP3A4) was evaluated. The different effects of the three compounds on their expression, protein level and activity was determined under specific PDT light (T0+, T6+) or dark conditions (T0- T6-). We found that HP or AR treatment affected the protein levels of MRP2 and P-gp, whereas HP decreased MRP2 and P-gp expression mostly in the T0+ and T6+ conditions, while AR decreased MRP2 in T0- and T6+. Moreover, HY PDT treatment induced the expression of MRP1. Our data demonstrate that HP or AR treatment in light or dark PDT conditions had an inhibitory effect on the activity of individual membrane transport proteins and significantly decreased CYP3A4 activity in HT-29 cells. We found that HP or AR significantly affected intracellular accumulation of HY in HT-29 colon adenocarcinoma cells. These results suggest that HY, HP and AR might affect the efficiency of anti-cancer drugs, through interaction with membrane transporters and CYP3A4. PMID- 27261576 TI - Combinatorial effects of geopropolis produced by Melipona fasciculata Smith with anticancer drugs against human laryngeal epidermoid carcinoma (HEp-2) cells. AB - The identification of natural products exerting a combined effect with therapeutic agents could be an alternative for cancer treatment, reducing the concentration of the drugs and side effects. Geopropolis (Geo) is produced by some stingless bees from a mixture of vegetable resins, gland secretions of the bees and soil. It has been used popularly as an antiseptic agent and to treat respiratory diseases and dermatosis. To determine whether Geo enhances the anticancer effect of carboplatin, methotrexate and doxorubicin (DOX), human laryngeal epidermoid carcinoma (HEp-2) cells were treated with Geo alone or in combination with each drug. Cell growth, cytotoxicity and apoptosis were evaluated using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release, and flow cytometry. Scratch assay was used to analyze cell migration and transmission electron microscopy to observe morphologic alterations. The influence of Geo on drug resistance was also investigated assessing P-glycoprotein (P-gp) action. Geo inhibited cell proliferation and migration. The combination Geo+DOX led to the highest cytotoxic activity and induced apoptosis, leading to loss of membrane integrity. Geo had no effect on P-gp-mediated efflux of DOX. Data indicate that Geo combined with DOX could be a potential clinical chemotherapeutic approach for laryngeal cancer treatment. PMID- 27261577 TI - Caffeic acid attenuates oxidative stress, learning and memory deficit in intra cerebroventricular streptozotocin induced experimental dementia in rats. AB - Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (p<0.001) learning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD. PMID- 27261578 TI - MicroRNA-128a-induced apoptosis in HTR-8/SVneo trophoblast cells contributes to pre-eclampsia. AB - INTRODUCTION: Pre-eclampsia (PE) can endanger the survival of the mother and fetus. Currently, the pathogenesis of PE is not completely understood and no fundamental therapeutics are available. The present study was performed to determine the function of miR-128a in HTR-8/SVneo trophoblast cells and to ascertain its underlying role in the pathogenesis of PE. METHODS: We investigated the function of miR-128a in HTR-8/SVneo cells by overexpressing. We analyzed the apoptosis of HTR-8/SVneo cells by performing apoptosis assays and measured the loss of mitochondrial membrane potential (Deltaym), the generation of reactive oxygen species (ROS) and caspase activity. In addition, miR-128a target genes were predicted. RESULTS: Using computer-based programs, we identified Bax as a direct target of miR-128a. In the apoptosis assays of HTR-8/SVneo cells, miR-128a decreased the Deltapsim, depleted ATP levels and increased ROS generation, cytochrome c release as well as caspase activation. Further studies showed that miR-128a induced the apoptosis of HTR-8/SVneo cells by down-regulating Bax through the mitochondrial apoptosis pathway. CONCLUSIONS: miR-128a is an up regulated miRNA in patient with PE. Our study demonstrated that the miR-128a induced apoptosis of HTR-8/SVneo cells may contribute to PE and miR-128a may be a novel potential therapeutic target for PE. PMID- 27261579 TI - Ginkgolide B functions as a determinant constituent of Ginkgolides in alleviating lipopolysaccharide-induced lung injury. AB - Ginkgolides are the major bioactive components of Ginkgo biloba extracts, however, the exact constituents of Ginkgolides contributing to their pharmacological effects remain unknown. Herein, we have determined the anti inflammatory effects of Ginkgolide B (GB) and Ginkgolides mixture (GM) at equivalent dosages against lipopolysaccharide (LPS)-induced inflammation. RAW 264.7 cell culture model and mouse model of LPS-induced lung injury were used to evaluate in vitro and in vivo effects of GB and GM, respectively. In RAW 264.7 cells, GB and GM at equivalent dosages exhibit an identical capacity to attenuate LPS-induced inducible nitric oxide synthase mRNA and protein expression and subsequent NO production. Likewise, GB and GM possess almost the same potency in attenuating LPS-induced expression and activation of nuclear factor kappa B (p65) and subsequent increases in tumor necrosis factor-alpha mRNA levels. In LPS induced pulmonary injury, GB and GM at the equivalent dosages have equal efficiency in attenuating the accumulation of inflammatory cells, including neutrophils, lymphocytes, and macrophages, and in improving the histological damage of lungs. Moreover, GB and GM at equivalent dosages decrease the exudation of plasma protein to the same degree, whereas GM is superior to GB in alleviating myeloperoxidase activities. Finally, though GB and GM at equivalent dosages appear to reduce LPS-induced IL-1beta mRNA and protein levels and IL-10 protein levels to the same degree, GM is more potent than GB to attenuate the IL-10 mRNA levels. Taken together, this study demonstrates that GB functions as the determinant constituent of Ginkgolides in alleviating LPS-induced lung injury. PMID- 27261580 TI - MiR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN. AB - PURPOSE: MicroRNA-454 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and function in non small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-454 in NSCLC tumorigenesis and development. METHODS: Using quantitative RT-PCR, we detected miR-454 expression in NSCLC cell lines and primary tumor tissues. The association of miR-454 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-454 on the biological behavior of NSCLC cells were investigated. At last, the potential regulatory function of miR-454 on PTEN expression was confirmed. RESULTS: miR-454 was found to be up-regulated in NSCLC tissues and cell lines. High miR-454 expression was closely correlated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis corroborated that miR-454 overexpression was an independent unfavourable prognostic factor for patients with NSCLC. Down-regulation of miR-454 could significantly reduce NSCLC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while up-regulation of miR-454 showed opposite effects. Further, PTEN was confirmed as a direct target of miR-454 by using Luciferase Reporter Assay. CONCLUSIONS: These findings indicate that miR 454 may act as an oncogene in NSCLC and would serve as a potential therapy target for this disease. PMID- 27261581 TI - Embryonic develop-associated gene 1 is overexpressed and acts as a tumor promoter in thyroid carcinoma. AB - Embryonic develop-associated gene 1 (EDAG-1), a hematopoietic tissue-specific protein, is usually highly expressed in the placenta, fetal liver, bone marrow and leukemia cells, but the expression status in normal or solid tumor tissues is rarely reported. In this study, we found that EDAG-1 was up-regulated in thyroid carcinoma tissues and cells. Knockdown of EDAG-1 suppressed proliferation and enhanced cisplatin-induced apoptosis of thyroid carcinoma cells. We also demonstrated that knockdown of EDAG-1 inactivated the phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway in vitro and in vivo. Moreover, knockdown of EDAG-1 suppressed tumorigenesis of thyroid carcinoma in vivo. Taken together, these results suggest that EDAG-1 regulates the proliferation and apoptosis of thyroid carcinoma via the PI3K/Akt signaling pathway. PMID- 27261582 TI - Silymarin-loaded Eudragit((r)) RS100 nanoparticles improved the ability of silymarin to resolve hepatic fibrosis in bile duct ligated rats. AB - Some nano-formulations of silymarin (SM), a drug commonly used for liver diseases, were developed to overcome its poor solubility and poor bioavailability; antifibrotic effect of these formulations has not been tested yet. In this study we aimed to formulate and evaluate silymarin-loaded Eudragit((r)) RS100 nanoparticles (SMnps) and to test the capability of SMnps to reverse an established fibrosis model. SMnps were prepared by solvent evaporation and nano-precipitation techniques. The influence of drug:polymer ratio, concentration of surfactant in the aqueous phase on particle size, drug entrapment efficiency (EE) % and in vitro drug releases were investigated. For in vivo evaluation, bile duct ligated (BDL)-rats were treated with either SM or SMnps every other day (125mg/kg) orally for 3 weeks started 3 weeks after BDL. Liver function tests, oxidative stress and fibrosis/fibrogenesis process were evaluated using biochemical and histopathological techniques. The formulation No (F4) of SMnps showed an average particle size of 632.28+/-12.15nm, a drug EE% of 89.47+/-1.65% and released the drug in a prolonged manner over 24h. The prepared SMnps were nearly spherical with smooth surfaces. In BDL-rats, treatments with either SM or SMnps corrected liver function and oxidative stress. Only SMnps was able to reverse the induced fibrosis; SMnps significantly decreased serum tumor necrosis factor- alpha (TNF-alpha), serum transforming growth factor- beta1 (TGF beta1), hepatic hydroxyproline and downregulated the hepatic expression of tissue inhibitor metalloproteinase-1 (TIMP-1) and cytokeratin-19 (CK-19), whilst increased hepatic hepatocytes growth factor (HGF) and upregulated the hepatic expression of matrix metalloproteinase-2 (MMP-2) and increased MMP-2/TIMP-1 ratio at mRNA level. Livers of rats treated with SMnps showed very little collagen in ECM and restored hepatic architecture as compared to either BDL rats or rats treated with SM. CONCLUSION: Formulation of silymarin as nanoparticles improved its ability to resolve cholestasis-induced liver fibrosis by restoring hepatic regenerative capabilities. Therefore, formulation of SMnps may represent a step forward in the field of anti-fibrotic drug development. PMID- 27261583 TI - Nobiletin protects against murine l-arginine-induced acute pancreatitis in association with downregulating p38MAPK and AKT. AB - Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell damage, oxidative stress, and inflammation of the pancreas. Nobiletin (3',4',5,6,7,8-hexamethoxyflavone), a major polymethoxy flavone, has shown health promoting properties in previous studies. Therefore, in this study, we investigated whether nobiletin protects against experimental AP induced with l arginine. C57BL/6 mice were treated with 25 or 50mg/kg nobiletin by intraperitoneal injection once daily for 14 consecutive days. AP was then induced in the mice with two intraperitoneal injections of l-arginine (4g/kg). The nobiletin treatment significantly reduced the plasma amylase levels, pancreatic myeloperoxidase activity, percentage of pancreatic necrosis, plasma proinflammatory factors, the generation of reactive oxygen species, cell apoptosis, tissue damage, and the expression of phosphorylated p38MAPK (p p38MAPK) and p-AKT. These results suggest that nobiletin is a new therapeutic method for l-arginine-induced AP in mice. PMID- 27261584 TI - The inhibiting effect of the Coptis chinensis polysaccharide on the type II diabetic mice. AB - In this paper, we investigated the effects of Coptis chinensis polysaccharide (CCP) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. CCP was prepared by extraction from Coptis chinensis and oral given to the mice. C57BL/6J mice in each of the 5 groups (eight mice per group) were given either the normal diet (ND) (D12450B, 10% kcal% fat; Research diet, New Brunswick, NJ, USA), HFD (D12451, 45% kcal% fat; Research diet, New Brunswick, NJ, USA), or HFD with CCP of differing hardness (500, 1000, and 2000ppm) for 20 weeks. Mice given an HFD with CCP showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that CCP improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that CCP recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, beta-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with CCP. CCP increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. CCP stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that CCP has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake. PMID- 27261585 TI - Lobetyol activate MAPK pathways associated with G1/S cell cycle arrest and apoptosis in MKN45 cells in vitro and in vivo. AB - AIM: The agent lobetyol, which is isolated from Lobelia chinensis, was previously shown to be cytotoxicity againts several cancer cell lines in published report. Today, we perform a study in vitro and in vivo to analyze its anti-carcinoma effect in MKN45 cells and to explore the molecular mechanism. MAIN METHODS: The growth inhibition of lobetyol on MKN45 cells was analyzed with MTT and flow cytometry. Hoechst 33342 staining and TUNEL cover glass staining were used to provide the visual evidence of apoptosis. Western blotting assay was performed to study the activation or blocking of related signaling pathways. KEY FINDINGS: Lobetyol induce apoptosis and cell cycle arrest in a time- and dose-dependent manner in MKN45 cells in our study. This process is mediated by the MAPK signaling pathways. This study confirmed the cytotoxicity of lobetyol in MKN45 cells and provided an insight into the molecular mechanism, which demonstrates the potential of lobetyol as an anti-tumor agent. PMID- 27261586 TI - Advances in biomarkers of biliary tract cancers. AB - Tumor biomarkers can be applied for early diagnosis or precise treatment, thereby leading to personalized treatment and better outcomes. Biliary tract cancers (BTCs) are a group of cancers that occurs in different locations and have different clinical or genetic properties. Though the incidence of BTCs is rare, BTCs are among the most lethal cancers in the world and all have very low 5-year survivals. Lack of efficient early diagnostic approaches or adjuvant therapies for BTCs are main reasons. These urge us to broaden the researches into BTC biomarkers. Although few progresses of diagnostic biomarkers for BTCs have been achieved, there are still some advances in prognostic, predictive and therapeutic areas. In this review, we will focus on these achievements. PMID- 27261587 TI - Combination of telmisartan with sildenafil ameliorate progression of diabetic nephropathy in streptozotocin-induced diabetic model. AB - Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the world. Several signaling pathways are involved in the pathogenesis of DN including elevation in level of angiotensin II, formation of advanced glycation end products (AGE), activation of protein kinase c (PKC), and lipid accumulation. These pathways activate one another mutually leading to oxidative stress, increasing expression of transforming growth factor beta-1(TGF-beta 1) and release of interleukins and adhesion molecules, so the aim of this study is to interrupt more than pathogenic pathway to ameliorate the progression of DN. In the present study, white male rats (N=48) were divided into six groups (8 rats each), the first two groups served as normal control and a control vehicle group while the remaining four groups were rendered diabetic by a single intraperitoneal injection of Streptozotocin (STZ) and being left for 4 weeks to develop DN. Thereafter, the rats were divided into DN group, DN group receiving Telmisartan or Sildenafil or Telmisartan Sildenafil combination. After the specified treatment period, urine samples were collected (using metabolic cages) to measure proteinuria, animals were then euthanized, blood and tissue samples were collected for measurement of Blood glucose,BUN, S.Cr, LDL, NO, TGF-beta1, IL 1beta, AGEPs, and SOD. The combination therapy showed significant decrease in BUN, S.Cr,LDL, TGF-beta1, IL-1beta, Proteinuria and AGEPs and significant increase in SOD and NO. The findings showed that combination therapy was able to ameliorate DN and that the effects were superior to the single drugs alone. PMID- 27261588 TI - Extracellular matrix protein ITGBL1 promotes ovarian cancer cell migration and adhesion through Wnt/PCP signaling and FAK/SRC pathway. AB - Despite the advances in cancer treatment and the progresses in tumor biological, ovarian cancer remains a bad situation. In current study, we found a novel extracellular matrix protein, ITGBL1, which is highly expressed in ovarian cancer tissues by immunohistochemistry examination. The expression pattern of ITGBL1 in malignant tissues inspired us to investigate its role in ovarian cancer progression. Both loss- and gain-function assays revealed that ITGBL1 could promote ovarian cancer cell migration and adhesion. As it's a secreted protein, we further used recombinant ITGBL1 protein treated cancer cells and found that ITGBL1 promotes cell migration and adhesion in a concentration dependent manner. Furthermore, we found that ITGBL1 not only influences the activity of Wnt/PCP signaling but also affects FAK/src pathway in vitro. Taken together, our results suggest that highly expressed ITGBL1 could promotes cancer cell migration and adhesion in ovarian cancer and as a secreted protein, ITGBL1 might be a novel biomarker for ovarian cancer diagnosis. PMID- 27261589 TI - Overexpression of lncRNA AFAP1-AS1 correlates with poor prognosis and promotes tumorigenesis in colorectal cancer. AB - Accumulating evidence has shown that long non-coding RNAs (lncRNAs) are emerging as key molecules in human malignancies. The lncRNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) was recently found deregulated in several cancers. However, its expression pattern, clinical performance and functional roles in colorectal cancer (CRC) had not been addressed. In this study, we found that AFAP1-AS1 was aberrantly over-expressed in CRC tissues and closely correlated with tumor size, TNM stage and distant metastasis. Kaplan-Meier analysis indicated that patients with high level of AFAP1-AS1 expression had poorer overall survival (OS) and disease-free survival (DFS). Univariate and multivariable Cox regression analyses further identified that up-regulated AFAP1 AS1 might act as an independent prognostic factor for CRC patients. Moreover, AFAP1-AS1 depletion resulted in the inhibition of CRC cell proliferation and colony formation. In addition, AFAP1-AS1 knockdown induced G0/G1 cell cycle arrest in CRC cells. Taken together, our findings indicate that AFAP1-AS1 is significantly up-regulated in CRC, which may act as an oncogene and correlate with tumor malignant progression and poor prognosis of CRC. This study may shed a new light on better understanding the pathogenesis of CRC. Moreover, AFAP1-AS1 also may be a promising diagnostic and therapeutic target for this deadly disease. PMID- 27261591 TI - AstragalosideII inhibits autophagic flux and enhance chemosensitivity of cisplatin in human cancer cells. AB - Inhibition of autophagy has been daily served as a promising anti-cancer treatment strategies. AstragalosideII (ASII), a main compound isolated from traditional Chinese medicine Radix Astragali, has been demonstrated to inhibit autophagy and reverse multidrug resistance in human hepatic cancer cells Bel 7402/5-FU. In this study, we inspected the function and mechanisms of ASII and cisplatin on autophagy in human cancer cells, and assessed the effect of ASII on cisplatin-induced apoptosis. We found ASII increased LC3II protein level, p62 protein level and GFP-LC3 puncta accumulation in human cancer cells. Furthermore, we found that ASII downregulated the expression of lysosomal cathepsinB/L (CTSB/L) in EBSS medium and affected the lysosomal acidification. Finally, we demonstrated that cisplatin induced protective autophagy which was involved of PI3K/Akt/mTOR pathway. Moreover, ASII in conjunction with cisplatin significant reduced cell viability, arrested in S phase and increased apoptosis. In conclusion, these findings suggested that ASII served as autophagy inhibitor which restored chemosensitivity of anticancer agent cisplatin and enhanced tumor cell death. PMID- 27261590 TI - Marine drug Haishengsu increases chemosensitivity to conventional chemotherapy and improves quality of life in patients with acute leukemia. AB - BACKGROUND: Pharmacological management of acute leukemia remains a challenge. A seashell protein Haishengsu (HSS) has been found to exert anticancer activities in recent in vitro studies. The aim of this study was to determine whether the addition of HSS to the conventional chemotherapies would increase chemosensitivity and improves quality of life in patients with acute leukemia. METHODS: Two hundred and forty-eight patients with acute leukemia were enrolled in a double-blind, and placebo-controlled study. In addition to conventional chemotherapy, 142 patients received HSS and 106 received placebo. In an in vitro study, the expression of P-gp was evaluated by flow cytometry in a drug-resistant leukemia cell line (K562/ADM cells). Sorcin was examined by Western blot. RESULTS: The complete remission rates in the HSS treatment group were all higher than in the placebo group with non-relapsing leukemia and relapsed leukemia (p<0.05). Less patients in the HSS group experienced gastrointestinal side effects from chemotherapy, whereas more patients had increased food take and an increase in Karnofsky performance status (KPS) score (p<0.01). In vitro, the expression of P-gp and sorcin in the HSS treated cells were lower than in the control group cells (p<0.01). CONCLUSION: When added to conventional chemotherapy, HSS improves the complete remission rates and quality of life in patients with acute leukemia. The in vitro findings indicate that suppression of P-gp and sorcin genes in leukemia cells may be involved in the beneficial effects of HSS. PMID- 27261592 TI - Investigation of the anti-glioma activity of Oviductus ranae protein hydrolysate. AB - Oviductus Ranae is the dry oviducts of Rana temporaria chensinensis, and it has been reported to have a range of biological activities. This study aimed to investigate the effects of Oviductus Ranae protein hydrolysate (ORPH) on human glioma C6 cell proliferation and apoptosis in vitro and in vivo. Following in vitro treatment, cell viability and colony formation assays showed that ORPH inhibited C6 cell proliferation. In addition, the results of western blotting also demonstrated that ORPH effectively regulated the expression of the apoptosis related proteins, cleaved caspase-3, Bax and Bcl-2, DNA staining and flow cytometry analysis demonstrated that ORPH significantly promoted apoptosis in this cell line, a finding that was confirmed in vivo using terminal deoxynucleotidyl transferase dUTP nick end labeling. Further investigation demonstrated that ORPH increased apoptosis by modulating the release of inflammatory cytokines and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway; this was demonstrated using a PI3K/AKT inhibitor (NVP-BEZ235). In summary, the present study suggested that ORPH promoted apoptosis and inhibited glioma cell proliferation by influencing the PI3K/AKT signaling pathway. PMID- 27261593 TI - Quantitative methods in electroencephalography to access therapeutic response. AB - Pharmacometrics or Quantitative Pharmacology aims to quantitatively analyze the interaction between drugs and patients whose tripod: pharmacokinetics, pharmacodynamics and disease monitoring to identify variability in drug response. Being the subject of central interest in the training of pharmacists, this work was out with a view to promoting this idea on methods to access the therapeutic response of drugs with central action. This paper discusses quantitative methods (Fast Fourier Transform, Magnitude Square Coherence, Conditional Entropy, Generalised Linear semi-canonical Correlation Analysis, Statistical Parametric Network and Mutual Information Function) used to evaluate the EEG signals obtained after administration regimen of drugs, the main findings and their clinical relevance, pointing it as a contribution to construction of different pharmaceutical practice. Peter Anderer et. al in 2000 showed the effect of 20mg of buspirone in 20 healthy subjects after 1, 2, 4, 6 and 8h after oral ingestion of the drug. The areas of increased power of the theta frequency occurred mainly in the temporo-occipital - parietal region. It has been shown by Sampaio et al., 2007 that the use of bromazepam, which allows the release of GABA (gamma amino butyric acid), an inhibitory neurotransmitter of the central nervous system could theoretically promote dissociation of cortical functional areas, a decrease of functional connectivity, a decrease of cognitive functions by means of smaller coherence (electrophysiological magnitude measured from the EEG by software) values. Ahmad Khodayari-Rostamabad et al. in 2015 talk that such a measure could be a useful clinical tool potentially to assess adverse effects of opioids and hence give rise to treatment guidelines. There was the relation between changes in pain intensity and brain sources (at maximum activity locations) during remifentanil infusion despite its potent analgesic effect. The statement of mathematical and computational aspects in the use of clinical data is frequent and elucidation of these aspects we use PhysioNet https://www.physionet.org/, Clinical Database online supported by the National Institutes of Health (National Institutes of Health of United States of America/NIH-USA) for the acquisition of EEG data and the Matlab program to do the simulations with the methods and thus create opportunities greater understanding. PMID- 27261594 TI - Clinical aspects of urea cycle dysfunction and altered brain energy metabolism on modulation of glutamate receptors and transporters in acute and chronic hyperammonemia. AB - In living organisms, nitrogen arise primarily as ammonia (NH3) and ammonium (NH4(+)), which is a main component of the nucleic acid pool and proteins. Although nitrogen is essential for growth and maintenance in animals, but when the nitrogenous compounds exceeds the normal range which can quickly lead to toxicity and death. Urea cycle is the common pathway for the disposal of excess nitrogen through urea biosynthesis. Hyperammonemia is a consistent finding in many neurological disorders including congenital urea cycle disorders, reye's syndrome and acute liver failure leads to deleterious effects. Hyperammonemia and liver failure results in glutamatergic neurotransmission which contributes to the alteration in the function of the glutamate-nitric oxide-cGMP pathway, modulates the important cerebral process. Even though ammonia is essential for normal functioning of the central nervous system (CNS), in particular high concentrations of ammonia exposure to the brain leads to the alterations of glutamate transport by the transporters. Several glutamate transporters have been recognized in the central nervous system and each has a unique physiological property and distribution. The loss of glutamate transporter activity in brain during acute liver failure and hyperammonemia is allied with increased extracellular brain glutamate concentrations which may be conscientious for the cerebral edema and ultimately cell death. PMID- 27261595 TI - MDC1-AS, an antisense long noncoding RNA, regulates cell proliferation of glioma. AB - BACKGROUND: Growing number of long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer origination and progression. A lncRNA, mediator of DNA damage checkpoint protein 1antisense RNA (MDC1-AS), with unknown function, is the antisense transcript of tumor suppressor MDC1. METHOD: In this study, we investigated the expression pattern and functional role of lncRNA MDC1-AS in glioma by using real time PCR and gain-/loss-of-function studies. RESULT: The results showed that the expression levels of lncRNA MDC1-AS and MDC1 were significantly downregulated in glioma tissues compared with normal brain tissues, and in glioma cell lines U87MG, U251 and HEB. Overexpression of MDC1-AS resulted in significant inhibition of cell proliferation and cell cycle in U87MG and U251. We also found that MDC1-AS expression was positively correlated with MDC1 expression. In addition, the inhibitory role of MDC1-AS was remarkably diminished when MDC1 was knockdown. CONCLUSION: Together, the results suggest that MDC1-AS is a novel tumor suppressor through up-regulation of its antisense tumor suppressing gene MDC1 in glioma and leads us to propose that MDC1-AS may serve as a potential biomarker and therapeutic target for glioma. PMID- 27261596 TI - Prognostic value of plasma D-dimer levels in patients with small-cell lung cancer. AB - OBJECTIVE: Little data exists with respect to the relationship between the level of plasma D-dimer and prognosis of small cell lung cancer (SCLC).The aim of this study was to investigate whether the levels of plasma D-dimer could be served as a prognostic factor in patients with SCLC. METHODS: A total of 393 patients with SCLC were addressed in the present retrospective study. Plasma D-dimer levels were measured by immunoturbidimetric assay. The correlation between plasma D dimer levels and other clinical features, progression free survival (PFS) and overall survival (OS) was analyzed statistically. RESULTS: The plasma D-dimer levels were significantly correlated with karnofsky performance status (KPS), tumor stage, number of metastatic sites, and treatment response. The PFS and OS of patients with elevated D-dimer levels before chemotherapy were significantly shorter than that of patients with normal D-dimer levels (PFS: 6.2 months versus 9.6 months, P<0.001; OS: 15.7 months versus 24.4 months, P<0.001). The patients with D-dimer levels converting from high to normal had better PFS and OS than those with D-dimer levels remaining high after two cycles of chemotherapy. According to multivariate analysis, elevated D-dimer level was confirmed to be an independent prognostic factor for worse survival. CONCLUSIONS: Elevated plasma D dimer level could be served as an independent determinant of poor prognosis in patients with SCLC. PMID- 27261597 TI - Effects of chemotherapy agents on Sphingosine-1-Phosphate receptors expression in MCF-7 mammary cancer cells. AB - Sphingosine-1-phosphate (S1P) is a potent bioactive sphingolipid involved in the regulation of cell proliferation and cancer progression. Increased expression of S1P receptors has been detected in advanced breast tumours with poor prognosis suggesting that S1P receptors might control tumour response to chemotherapy. However, it remains unclear how the levels of S1P receptor expression are influenced by chemotherapy agents. Western immunoblotting, PCR analysis and fluorescent microscopy techniques were used in this study to analyze expression patterns of S1P receptors 2 and 3 (S1P2/S1P3) in MCF-7 breast adenocarcinoma cells treated by Tamoxifen (TAM) and/or Medroxyprogesterone acetate (MPA). We found that TAM/MPA induce downregulation of S1P3 receptors, but stimulate expression of S1P2. According to cell viability and caspase activity analyses, as expected, TAM activated apoptosis. We also detected TAM/MPA-induced autophagy marked by formation of macroautophagosomes and increased level of Beclin 1. Combined application of TAM and MPA resulted in synergistic apoptosis- and autophagy-stimulating effects. Assessed by fluorescent microscopy with autophagosome marker LAMP-2, changes in S1P receptor expression coincided with activation of autophagy, suggestively, directing breast cancer cells towards death. Further studies are warranted to explore the utility of manipulation of S1P2 and S1P3 receptor expression as a novel treatment approach. PMID- 27261598 TI - Effects of nitric oxide system and osmotic stress on Aquaporin-1 in the postnatal heart. AB - Aquaporin-1 (AQP1) is expressed in the heart and its relationship with NO system has not been fully explored. The aims of this work were to study the effects of NO system inhibition on AQP1 abundance and localization and evaluate AQP1 S nitrosylation in a model of water restriction during postnatal growth. Rats aged 25 and 50days (n=15) were divided in: R: water restriction; C: water ad libitum; RL: L-NAME (4mg/kgday)+water restriction; CL: L-NAME+water ad libitum. AQP1 protein levels, immunohistochemistry and S-nitrosylation (colocalization of AQP1 and S-nitrosylated cysteines by confocal microscopy) were determined in cardiac tissue. We also evaluated the effects of NO donor sodium nitroprusside (SNP) on osmotic water permeability of cardiac membrane vesicles by stopped-flow spectrometry. AQP1 was present in cardiac vascular endothelium and endocardium in C and CL animals of both ages. Cardiac AQP1 levels were increased in R50 and RL50 and appeared in cardiomyocyte plasma membrane. No changes in AQP1 abundance or localization were observed in R25, but RL25 group showed AQP1 presence on cardiomyocyte sarcolemma. AQP1 S-nitrosylation was increased in R25 group, without changes in the 50-day-old group. Cardiac membrane vesicles expressing AQP1 presented a high water permeability coefficient and pretreatment with SNP decreased water transport. Age-related influence of NO system on AQP1 abundance and localization in the heart may affect cardiac water homeostasis during hypovolemic state. Increased AQP1 S-nitrosylation in the youngest group may decrease osmotic water permeability of cardiac membranes, having a negative impact on cardiac water balance. PMID- 27261599 TI - 5,7,4'-Trihydroxy-6,8-diprenylisoflavone and lupalbigenin, active components of Derris scandens, induce cell death on breast cancer cell lines. AB - BACKGROUND: Natural products are a potential source for cancer chemotherapeutic development. This current study was performed to investigate the anti-tumor potential of 5,7,4'-trihydroxy-6,8-diprenylisoflavone (TD) and lupalbigenin (LB), plant flavonoids found in Derris scandens Benth (family: Leguminosae), in cancer and normal cell lines. METHODS: The human breast cancer cell lines MCF-7, MDA-MB 231 and MDA-MB-468, the human colon cancer cell line SW-620, and the mouse fibroblast cell line L-929 were used to test their anti-cancer activity. Apoptotic cell levels were measured by staining with annexin-V and propidium iodide and Western blot analysis was performed to confirm the apoptotic mechanism. RESULTS: The results revealed that TD and LB showed specific cytotoxicity against MDA-MB-231 and MCF-7 cells. To elucidate mode of cell death via cytotoxic activities, breast cancer cell lines were treated. TD and LB induced MDA-MB-231 and MCF-7 cells to apoptosis, with the highest number of apoptotic cells at 24 and 72h, respectively. Furthermore, TD and LB inhibited cell cycle progression via up-regulation of p21. Both compounds stimulated apoptosis through down-regulation of bcl-2, up-regulation of bax and releasing of cytochrome C proteins. CONCLUSIONS: TD and LB have significant anti-cancer effects against human breast cancer cells via cell cycle arrest and the induction of apoptosis through mitochondria signaling pathways, and may be potential anti cancer agents for the treatment of breast cancer. PMID- 27261600 TI - Grape seed and skin extract protects against bleomycin-induced oxidative stress in rat lung. AB - INTRODUCTION: Lung fibrosis is a common side effect of the chemotherapeutic agent bleomycin and current evidence suggests that reactive oxygen species play a key role in the development of lung injury. We examined whether grape seed and skin extract (GSSE), a polyphenolic mixture exhibiting antioxidant properties, is able to protect against bleomycin-induced lung oxidative stress and injury. METHODS: Rats were pre-treated during three weeks either with vehicle (ethanol 10% control) or GSSE (4g/kg), then administered with a single high dose bleomycin (15mg/kg) at the 7th day. RESULTS: Bleomycin increased lung lipoperoxidation, carbonylation and decreased antioxidant enzyme activities as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Bleomycin also induced copper depletion from the lung and iron accumulation within the lung, but had no effect on either zinc nor manganese. Correlatively bleomycin decreased the copper associated enzyme tyrosinase, increased the zinc dependent lactate dehydrogenase (LDH) and did not affect the manganese dependent glutamine synthetase. GSSE efficiently counteracted almost all bleomycin-induced oxidative stress, biochemical and morphological changes of lung tissue. CONCLUSION: Data suggest that GSSE exerts potent antioxidant properties that could find potential application in the protection against bleomycin-induced lung fibrosis. PMID- 27261601 TI - Histone deacetylase inhibitor sulforaphane: The phytochemical with vibrant activity against prostate cancer. AB - Epigenetic modifications are closely involved in the patho-physiology of prostate cancer. Histone deacetylases (HDACs), the transcriptional corepressors have strong crosstalk with prostate cancer progression as they influence various genes related to tumour suppression. HDACs play a marked role in myriad of human cancers and as such are emerging as striking molecular targets for anticancer drugs and therapy. Histone deacetylase inhibitors (HDACi), the small-molecules interfering HDACs are emerging as promising chemotherapeutic agents. These inhibitors have shown multiple effects including cell growth arrest, differentiation and apoptosis in prostate cancer. The limited efficacy of HDACi as single agents in anticancer therapy has been strongly improved via novel therapeutic strategies like doublet therapy (combined therapy). More than 20HDACi have already entered into the journey of clinical trials and four have been approved by FDA against diverse cancers. This review deals with plant derived HDACi sulphoraphane (SFN; 1-isothiocyanato-4-(methylsulfinyl)-butane) and its potential role in prostate cancer therapy along with the underlying molecular mechanism being involved. The article further highlights the therapeutic strategy that can be utilized for sensitizing conventional therapy resistant cases and for acquiring the maximum therapeutic benefit from this promising inhibitor in the upcoming future. PMID- 27261602 TI - Curcumin protects cardiac myocyte against hypoxia-induced apoptosis through upregulating miR-7a/b expression. AB - OBJECTIVE: Curcumin has properties of anti-inflammation, anti-oxidation, anti infection and anti-tumor, benefiting for the treatment of many diseases. The present study was aimed to investigate the role of curcumin in myocardial infarction (MI) and its potential mechanism involving transcription factor specific protein 1 (SP1). METHODS: After receiving curcumin, C57BL/6 mice subjected to left anterior descending (LAD) coronary artery occlusion to induce MI model. Infarct size was measured by triphenyl tetrazolium chloride staining. In vitro experiments, mouse cardiac myocytes (MCM) subjected to hypoxia after the incubation of curcumin, miR-7a/b and SP1 expression levels were detected by real time PCR and western blot. Caspase-3 activity and TUNEL assay were performed to assess the cell apoptosis. RESULTS: In animal experiments, curcumin significantly reduced the infarct size compared with the control. It also up-regulated miR-7a/b expression and down-regulated SP1 expression. In hypoxia-induced MCM, curcumin led to the decrease of cell apoptosis. Transfected MCM with miR-7a/b inhibitor, curcumin induced the decrease of cell apoptosis and SP1 expression was reversed. Transfected with pcDNA-SP1, the decrease of cardiac myocytes apoptosis after the treatment of curcumin was also reversed. CONCLUSION: Curcumin pre-treatment protected against hypoxia-induced cardiac myocytes apoptosis through the up regulation of miR-7a/b and the down-regulation of SP1 expression. PMID- 27261603 TI - Photodynamic efficiency of a chlorophyll-a derivative in vitro and in vivo. AB - This paper reports the antitumor activity of a chlorophyll-a derivative, 2-[1 hydroxyethyl]-2-devinylpyropheophorbide-a (HEPa). Photophysical characteristics of HEPa were measured. And its cytotoxicity, intracellular localization, biodistribution, efficiency of photodynamic therapy (PDT), histological analysis were investigated using human bile duct carcinoma cells (QBC-939) and QBC-939 tumor bearing BABL/c nude mice as animal model. The results showed that HEPa was localized mainly within the cytoplasmic region and partially in lysosome. Biodistribution of HEPa in QBC-939 tumor bearing BABL/c nude mice showed its fast rate of clearance and high tumor selectivity. In vitro, HEPa had low dark toxicity and high photoxicity against QBC-939 cells. The inhibition rate of QBC 939 tumor could increase up to 92.3%, and H&E staining confirmed that HEPa could cause serious damage to the tumor with light dose of 100J/cm(2), implying that HEPa has potential to be a new antitumor candidate for photodynamic therapy (PDT). PMID- 27261604 TI - Long-term exercise training as a modulator of mammary cancer vascularization. AB - BACKGROUND: Breast cancer remains a leading cause of death by cancer worldwide. It is commonly accepted that angiogenesis and the expression of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A) is associated with the increased risk of metastasis and poor patient outcome. OBJECTIVE: This work aimed to evaluate the effects of long-term exercise training on the growth and vascularization of mammary tumors in a rat model. MATERIALS AND METHODS: Fifty female Sprague-Dawley rats were divided into four groups: two N-methyl-N nitrosourea (MNU)-exposed groups (exercised and sedentary) and two control groups (exercised and sedentary). MNU was administered once, intraperitoneally at 7 weeks-old. Animals were then exercised on a treadmill for 35 weeks. Mammary tumors were evaluated using thermography, ultrasonography [Power Doppler (PDI), B Flow and contrast-enhanced ultrasound (CEUS)], and immunohistochemistry (VEGF-A). RESULTS: Both, MNU sedentary and exercised groups showed 100% of tumor incidence, but exercised animals showed less tumors with an increased latency period. Exercise training also enhanced VEGF-A immunoexpression and vascularization (microvessel density, MVD) (p<0.05), and reduced histological aggressiveness. Ultrasound and thermal imaging analysis confirmed the enhanced vascularization of tumors on exercised animals. CONCLUSION: Long-term exercise training increased VEGF-A expression, leading to enhanced tumor vascularization and reduced tumor burden, multiplicity and histological aggressiveness. PMID- 27261606 TI - Selective inhibition of EZH2 by ZLD10A blocks H3K27 methylation and kills mutant lymphoma cells proliferation. AB - EZH2 (Enhancer of zeste homolog 2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is involved in repressing gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation. EZH2 overexpression is implicated in tumorigenesis and has been a candidate oncogene in several tumor types. Recently, point mutations of EZH2 at Tyr641 and Ala677 were identified in diffuse large B cell lymphoma and follicular lymphoma, where they drive H3K27 hypertrimethylation and cancer progression. Here, we reported a novel, highly potent and selective small molecule inhibitor of EZH2, ZLD10A, which inhibited wild-type and mutant versions of EZH2 with nanomolar potency and had greater than 1000-fold selectivity against 10 other histone methyltransferases. Our results have shown that the compound suppressed global H3K27 methylation and cause the anti-proliferation effects in a concentration- and time-dependent manner in DLBCL cell lines. These results demonstrated that ZLD10A, as a novel EZH2 inhibitor, could be a potential promising agent for the treatment of EZH2 mutant lymphoma. PMID- 27261605 TI - Saikosaponin a functions as anti-epileptic effect in pentylenetetrazol induced rats through inhibiting mTOR signaling pathway. AB - OBJECTIVE: Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure. METHODS: PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL 1beta and TNF-alpha were then determined. RESULTS: In PTZ induced rat, SSa significantly reduced seizure severity and duration while markedly elevated seizure latency, and it also down-regulated hippocampal p-mTOR, p-70S6K, L-1beta and TNF-alpha expression. In hippocampal neurons exposed to PTZ, p-mTOR and p 70S6K expression levels were also decreased by SSa. Pre-incubated hippocampal neurons with leucine, an mTOR agonist, reversed the effects of SSa on decreasing cytokines expression and inhibiting cell apoptosis. The treatment of mTOR inhibitor rapamycin prevented against the increase of cytokines expression and hippocampal neuron apoptosis induced by PTZ. Leucine also canceled the alleviation of seizures and induction of hippocampal caspase-3 activity in PTZ induced rat with the treatment of SSa. CONCLUSION: SSa protects against PTZ induced epileptic seizure and hippocampal neuron apoptosis through inhibiting mTOR signaling pathway. PMID- 27261607 TI - Antidepressant effect of pramipexole in mice forced swimming test: A cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway. AB - Pramipexole is a dopamine D2 receptor agonist indicated for treating Parkinson disorder. This study was aimed to investigate the effect of pramipexole in forced swimming test (FST) in mice and the possible involvement of activation of D2 receptors and inhibition of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) on this effect. Intraperitoneal administration of pramipexole (1-3mg/kg) reduced the immobility time in the FST similar to fluoxetine (20mg/kg, i.p.). This effect of pramipexole (1mg/kg, i.p.) was ceased when mice were pretreated with haloperidol (0.15mg/kg, i.p,) and sulpiride (5mg/kg, i.p) as D2 receptor antagonists, NMDA (75mg/kg,i.p.), l arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.05mg/kg, i.p., a NMDA receptor antagonist) l-NG-Nitro arginine methyl ester (l NAME, 10mg/kg, i.p., a non-specific nitric oxide synthase (NOS) inhibitor), 7 nitroindazole (30mg/kg, i.p., a neuronal NOS inhibitor) and methylene blue (10mg/kg, i.p.), an inhibitor of both NOS and soluble guanylyl cyclase (sGC) in combination with the sub-effective dose of pramipexole (0.3mg/kg, i.p.) reduced the immobility. Altogether, our data suggest that the antidepressant-like effect of pramipexole is dependent on the activation of D2 receptor and inhibition of either NMDA receptors and/or NO-cGMP synthesis. These results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of pramipexole and reinforce the role of D2 receptors, NMDA receptors and l-arginine NO-GMP pathway in the antidepressant mechanism of this agent. PMID- 27261608 TI - Tumor suppressor microRNAs: Targeted molecules and signaling pathways in breast cancer. AB - Breast cancer is the most common type of cancer in women whose prevalence is increasing every year. Common strategies for diagnosis, prognosis and specific treatment of breast cancer need improvements to increase patients' survival. For this reason, there is growing number of efforts world-wide with molecular approaches. With the advent of microRNAs (miRNAs), they have been interested for almost all aspects of tumorgenesis and correlation of breast cancer and microRNAs was discovered for the first time in 2005. MiRNAs form a group of small noncoding RNAs which participate in regulation of gene expression and subsequently several biological processes and pathogenesis of various diseases. As other cancers, miRNAs involved in breast cancer are classified in two groups: the first group is tumor inducing miRNAs (also called oncomirs) that can induce tumor initiation and progression, and their expression is increased in cancerous cells. The second group is tumor suppressor miRNAs. In normal situation, tumor suppressor miRNAs prevent beginning and progression of breast cancer through suppressing the expression of various oncogenes. In this review we will give a general overview about miRNAs and breast cancer, and in the following, more discussion about tumor suppressor miRNAs, with focus on the best known of them and their targeted oncogenes and signaling pathways. Finally, we will point to application of this group of miRNAs in diagnosis, prognosis and treatment of patients. PMID- 27261609 TI - The protective effect of juglanin on fructose-induced hepatitis by inhibiting inflammation and apoptosis through TLR4 and JAK2/STAT3 signaling pathways in fructose-fed rats. AB - High fructose-feeding is an essential causative factor leading to the development and progression of hepatitis associated with high levels of endotoxin (LPS). Juglanin, as a natural compound extracted from the crude Polygonum aviculare, displayed inhibitory activity against inflammation response and cancer growth. However, researches about its role on anti-inflammation and apoptosis are far from available. Here, it is the first time that juglanin was administrated to investigate whether it inhibits fructose-feeding-induced hepatitis in rats and to elucidate the possible mechanism by which juglanin might recover it. Fructose feeding rats were orally administrated with juglanin of 5, 10 and 20mg/kg for 6 weeks, respectively. Juglanin exerted prevention of fructose-feeding-stimulated increased LPS levels, accelerated alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and up-regulated inflammatory cytokines expression in serum, mainly including tumor necrosis factor-alpha (TNF a), Interleukin 1beta (IL-1beta), Interleukin 6 (IL-6) and Interleukin 18 (IL 18). Meanwhile, toll-like receptor 4 (TLR4)-modulated mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-kappaB) and apoptosis-related Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway are involved in the progression of hepatic injury and inflammation. And juglanin was found to suppress fructose-feeding-induced activation of these signaling pathways compared with the model group administrated only with fructose. These results indicate that juglanin represses inflammatory response and apoptosis via TLR4-regulated MAPK/NF-kappaB and JAK2/STAT3 signaling pathway respectively in rats with hepatitis induced by LPS for fructose-feeding. Treatment of juglanin might be an effective therapeutic strategy for preventing hepatitis. PMID- 27261610 TI - Protective effect of Berberis vulgaris fruit extract against Paraquat-induced pulmonary fibrosis in rats. AB - BACKGROUND: Pulmonary fibrosis induced by paraquat (PQ) has caused a large number of human fatalities all over the world, especially in Asian region. The main potential mechanism of PQ toxicity has been thought to be mediated by ROS. The present study was designed to evaluate the efficacy of the Berberis vulgaris fruit extract (BVFE) against PQ-induced pulmonary fibrosis in rats. METHODS: Forty male rats were randomly divided into five experimental groups each containing eight rats. Groups 1 and 2, served as a negative and positive control and received a single dose of intratracheal instillation of saline and PQ (20mg/kg), respectively. Groups 3-5 were treated with different doses of BVFE (100, 200, 400mg/kg/day, orally) 1 week before the PQ injection and continued for 3 weeks. The rats were sacrificed 21days after PQ. Malondialdehyde (MDA), Hydroxyproline, inflammatory and fibrogenic cytokine tumor necrosis factor (TNF) alpha, interleukin (IL)-6 and transforming growth factor (TGF)-beta1 in lung tissue were determined. Presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in lung were evaluated microscopically by hematoxylin and eosin (H&E) staining. Dried extract was standardized by amount of berberine by HPTLC methods by silica gel plate. RESULTS: The results showed that PQ could significantly increase the lung MDA, hydroxyproline, TNF-alpha, IL-6 and TGF-beta1 levels. BVFE ameliorated the biochemical and histological lung alterations induced by PQ. CONCLUSIONS: The present study indicates the hydroalcolic extract of Berberis vulgaris fruit has beneficial effects in rat pulmonary fibrosis induced by PQ in a dose-dependent manner, possibly by anti oxidant and anti- inflammatory properties, which might be due to its berberine alkaloid content. PMID- 27261611 TI - Protection of rats spinal cord ischemia-reperfusion injury by inhibition of MiR 497 on inflammation and apoptosis: Possible role in pediatrics. AB - MicroRNAs are extensively included in the pathogenesis and progression of many diseases by inhibiting target gene expression. Recently, studies have demonstrated that microRNA-497 (miR-497) may be implicated in human breast cancer that miR-497 predicts the prognosis of breast cancer patients from the posttranscriptional level. However, the specific function of miR-497 in spinal cord ischemia-reperfusion (IR) injury is far from clear nowadays. The present study was designed to determine the role of miR-497 in spinal cord IR injury and investigate the underlying spinal cord protective mechanism. The rat spinal cord IR injury model was performed by occluding the left anterior descending coronary artery for 30 min, which is then followed by 12h reperfusion. As predicted, miR 497 over-expression markedly decreased the expression of IL-1 receptor associated kinase (IRAK1) and Cyclic AMP response element binding protein (CREB). Moreover, Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-kappaB) and Caspase-3, as miR-497 potential targets were significantly suppressed after miR-497 transfection, then preventing inflammatory cytokines and factors regulating apoptosis. We also found that tumor necrosis factor-a (TNF-alpha) and interleukin 1beta (IL-1beta) activity, pro-apoptotic related genes, such as extracellular regulated protein kinases (ERK), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL levels were all decreased associated with the down-regulation of IRAK1 and CREB. In conclusion, our data demonstrate that miR-497 could inhibit inflammation and apoptosis of spinal cord IR through its targets, IRAK1 of TLR4 and CREB signaling pathway. Thus, miR-497 may constitute a new therapeutic target for the prevention of spinal cord IR injury. PMID- 27261612 TI - Pterostilbene, a novel natural plant conduct, inhibits high fat-induced atherosclerosis inflammation via NF-kappaB signaling pathway in Toll-like receptor 5 (TLR5) deficient mice. AB - Atherosclerosis is a specific form of an artery wall thickens, a syndrome affecting arterial blood vessels due to a chronic inflammatory response in the walls of arteries, which is promoted by fat accumulation. Toll-like receptors (TLRs) play prominent roles in inflammatory responses. And TLR5 is overexpressed in several diseases. Here in our study, we investigated the effect of TLR5 in high fat-induced atherosclerosis via NF-kappaB signaling pathway modulating pro inflammatory cytokines releasing. Our results found that high fat induced atherosclerosis in wild type mice with fat accumulation and inflammatory response through NF-kappaB activation. Contrastly, TLR5 knockout mice displayed lower fat accumulation and ameliorated inflammation after high fat feeding with NF-kappaB inactivation. In addition, pterostilbene, as a natural dimethyl ether derivative of resveratrol mainly from blueberries, has diverse pharmacological activities, especially anti-inflammation. Our study also found that pterostilbene displayed inhibited role in suppressing inflammatory response through inactivating NF kappaB signaling pathway regulated by TLR5 down-regulation in high fat-induced mice. Moreover, in vitro experiments of vascular smooth muscle cells (VSMCs) challenged with LPS or TNF-alpha, further indicated that NF-kappaB was involved in atherosclerosis progression, leading to high secretion of pro-inflammatory cytokines. However, VSMCs from TLR5 deficient mice inhibited phosphorylated levels of NF-kappaB signalilng pathway, finally resulting in down-regulation of inflammatory cytokines. Notably, pterostilbene also displayed suppressed role in inflammatory response via NF-kappaB inactivity in LPS or TNF-alpha-induced VSMCs by decreasing TLR5 expression. The results above indicated a novel therapeutic strategy of pterostilbene to protect against atherosclerosis via TLR5 regulation for clinic treatment in the future. PMID- 27261613 TI - Effect of isoorientin on intracellular antioxidant defence mechanisms in hepatoma and liver cell lines. AB - Isoorientin (ISO) is considered one of the most important flavonoid-like compounds responsible for health benefits, including the prevention of liver damage as well as antioxidant, anti-inflammatory, and anti-nociceptive activities. Our previous study showed that ISO inhibited the proliferation of hepatoma cells through increasing intracellular ROS levels. Interestingly, ISO protects rat liver cells against hydrogen peroxide-induced oxidation stress by decreasing intracellular ROS levels. Why are there different effects of ISO on ROS in different physiological and pathophysiological circumstances? The present study investigated the effect of ISO on mitochondrial respiratory chain complexes and phase II detoxifying enzyme activities in human hepatoblastoma cancer cells (HepG2), buffalo rat liver cells (BRL-3A) and human liver cancer cells (HL-7702). The results showed that intracellular ROS levels and the protein expression of the respiratory chain complexes was significantly (p<0.01) higher in the HepG2 cells than in the BRL-3A and HL-7702 cells. Additionally, ISO notably (p<0.01) increased ROS levels in the HepG2 cells, while no significance was found in the BRL-3A and HL-7702 cells. Furthermore, in the HepG2 cells, the protein expression of the respiratory chain complexes and the phase II detoxifying enzyme activities and GSH content were decreased by ISO (p<0.01), while ISO, in a certain range, enhanced the expression of the protein complexes and the phase II detoxifying enzyme activities and GSH content in BRL-3A and HL-7702 cells. All of these results demonstrated, for the first time, that ISO possesses a notable hepatoprotective effect, which might be mediated through the respiratory chain complexes and phase II detoxifying enzyme activities. PMID- 27261614 TI - Effects of chlorogenic acid on adenine nucleotides hydrolyzing enzyme activities and expression in platelets of rats experimentally demyelinated with ethidium bromide. AB - BACKGROUND: The effects of chlorogenic acid (one of the major phenolic acid found in human diets) were investigated on the adenine nucleotides hydrolyzing enzymes; ecto-nucleotide pyrophosphatase/phophodiesterase (E-NPP), ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase), E-5'- nucleotidase and ecto adenosine deaminase (E-ADA) activities and expression in platelets of rats experimentally demyelinated with ethidium bromide. METHODS: Rats were divided into four groups of eight animals each. Group I rats were control rats; injected with saline (CT), group II rats were injected with saline and treated with chlorogenic acid (AC), group III rats were injected with 0.1% ethidium bromide (EB) and group IV rats were injected with 0.1% EB and treated with chlorogenic acid (EB+AC). The activities of the enzymes were analyzed using colorimetric methods, and the gene expression of NTPDase 1, 2 and 3 were analyzed using the polymerase chain reaction (PCR). RESULTS: The results revealed that there was a significant (P<0.01) reduction in E-NPP activity in EB group (1.63+/-0.10nmol p nitrophenol released/min/mg protein) when compared to CT group (2.33+/-0.14nmol p nitrophenol released/min/mg protein). However, treatment with chlorogenic acid significantly (P<0.05) increased E-NPP activity in EB group. Furthermore, no significant (P>0.05) change was observed in the E-NPP activity of EB+AC group (2.19+/-0.08nmol p-nitrophenol released/min/mg protein) when compared to CT group (2.33+/-0.14nmol p-nitrophenol released/min/mg protein). In addition, there was a significant (P<0.05) increase in AMP hydrolysis in EB rat group when compared to CT group. No significant (P>0.05) difference was observed in AMP hydrolysis between AC, AC+EB and CT groups. Conversely, there were no significant (P>0.05) differences in ATP and ADP hydrolyses between all the groups (AC, EB, AC+EB and CT groups). Likewise, there were no significant (P>0.05) changes in E-ADA activity and percentage platelet aggregation among all groups studied. Similarly, no significant (P>0.05) change was observed in the expression of E-NTPDase 1, 2 and 3 in all the groups tested. CONCLUSIONS: Our study revealed that chlorogenic acid may modulate the hydrolysis of adenine nucleotides in platelets of rats demyelinated and treated with chlorogenic acid via alteration of E-NPP and ecto 5'-nucleotidase activities. PMID- 27261615 TI - Polyphenols of Cassia tora leaves prevents lenticular apoptosis and modulates cataract pathology in Sprague-Dawley rat pups. AB - Cataract is a leading cause of visual impairment worldwide with multifactorial etiology and is a significant global health problem with increasing prevalence with age. Currently, no pharmacological measures are discovered to prevent and treat cataract and a significant number of epidemiological studies have suggested the potential role of antioxidants in the prevention of cataract by scavenging free radicals and preventing lens protein derangement and lenticular cell damage. The main goal of the present study is to evaluate Cassia tora leaves; an edible leafy vegetable employed in Ayurvedic and Chinese system of medicine for eye rejuvenation in preventing selenite-induced cataract in rat pups and to identify the active components that produce the effect. ECT pre-treatment effectively restored both enzymatic and metabolic antioxidant levels, membrane integrity and reduced metal accumulation and thus down-regulate epithelial cell death. Gene expression studies also confirmed these findings. ESI-MS analysis of ECT revealed the presence of chrysophanol, emodin, kaemferol, quercetin, stigmasterol and isoquercetin. The study suggests the possible role of C. tora in alleviating cataract pathology and presence of many anthraquinones and flavonoids. As it is an edible plant, the incorporation of these leaves in daily vegetables might prevent or delay the onset and maturation of cataract. PMID- 27261616 TI - MicroRNA-744 inhibited cervical cancer growth and progression through apoptosis induction by regulating Bcl-2. AB - Growing evidence suggests that microRNA plays an essential role in the development and metastasis of many tumor progressions, including cervical cancer. Aberrant miR-744 expression has been indicated in many growth of tumor, the mechanism of miR-744 inhibits both the proliferation and metastatic ability for cervical cancer remains unclear. Accumulating evidences reported that Bcl-2 signal pathway plays an important role in the cellular process, such as apoptosis, cell growth and proliferation. The goal of this study was to identify miR-744 that could inhibit the growth, migration, invasion, proliferation and metastasis of gastric cancer through targeting Bcl-2 expression. Real-time PCR (RT-qPCR) was used to quantify miR-744 expression in vitro and vivo experiments. The biological functions of miR-744 were determined via cell proliferation. Our study indicated that miR-744 targeted on Bcl-2, which leads to the inactivation of apoptosis signaling and the cell proliferation of cervical cancer cells, ameliorating cervical cancer growth and progression. In addition, both up regulation of miR-744 and down-regulation of Bcl-2 could stimulate Caspase-3 expression, promoting apoptosis of cervical cancer cells. Therefore, our research revealed the mechanistic links between miR-744 and Bcl-2 in the pathogenesis of cervical cancer through modulation of Caspase-3, leading to the inhibition of cervical cancer cell growth. And targeting miR-744 could be served as a novel strategy for future cervical cancer therapy clinically. PMID- 27261617 TI - Pharmacological or genetic inhibition of LDHA reverses tumor progression of pediatric osteosarcoma. AB - Reprogrammed energy metabolism is an emerging hallmark of cancer. Lactate dehydrogenase A (LDHA), a key enzyme involved in anaerobic glycolysis, is frequently deregulated in human malignancies. However, limited knowledge is known about its roles in the progression of osteosarcoma (OS). In this study, we found that LDHA is commonly upregulated in four OS cell lines compared with the normal osteoblast cells (hFOB1.19). Treatment with FX11, a specific inhibitor of LDHA, significantly reduced LDHA activity, and inhibited cell proliferation and invasive potential in a dose dependent manner. Genetic silencing of LDHA resulted in a decreased lactate level in the culture medium, reduced cell viability and decreased cell invasion ability. Meanwhile, silencing of LDHA also compromised tumorigenesis in vivo. Furthermore, knockdown of LDHA remarkably reduced extracellular acidification rate (ECAR) as well as glucose consumption. In the presence of 2-DG, a glycolysis inhibitor, LDHA-mediated cell proliferation and invasion were completely blocked, indicating the oncogenic activities of LDHA may dependent on Warburg effect. Finally, pharmacological inhibition of c-Myc or HIF1alpha significantly attenuated LDHA expression. Taken together, upregulated LDHA facilitates tumor progression of OS and might be a potential target for OS treatment. PMID- 27261618 TI - Targeted nano-delivery of novel omega-3 conjugate against hepatocellular carcinoma: Regulating COX-2/bcl-2 expression in an animal model. AB - The present approach enumerates the effectiveness of tuftsin tagged nano-liposome for the cytosolic transport of 2,6-di-isopropylphenol-linolenic acid conjugate against liver cancer in mice. Initially, the conjugate in its free form was examined for anticancer potential on HepG2 liver cancer cells. Induction of apoptosis and suppression of migration and adhesion of HepG2 cells confirmed the effectiveness of conjugate as an anticancer agent. After this, role of the conjugate entrapped in a nano-carrier was evaluated in animal model. The nano formulation comprising of conjugate bearing tuftsin tagged liposome was firsly characterized and then its therapeutic effect was determined. The nano formulation had 100-130nm size nanoparticles and showed sustained release of the conjugate in the surrounding milieu. The nano-formulation distinctly reduced the expression of COX-2, an important molecule that is vastly expressed in hepatocellular carcinoma. The utilization of in-house engineered nano-formulation was also successful in significantly up-regulating Bax and down-regulating bcl-2 gene expression eventually helping in better survival of treated mice. Histopathological analysis also revealed positive recovery of the general architecture and the violent death of cancer cells by apoptosis at tumor specific site. The site specific delivery of conjugate entrapped in tuftsin tagged liposomes was highly safe as well as efficaceous. Nano-formulation based approach showed a visible chemotherapeutic effect on liver cancer progression in experimental mice thereby making it a potential candidate for treatment of liver cancer in clinical settings. PMID- 27261619 TI - Neuroinformatics analyses reveal GABAt and SSADH as major proteins involved in anticonvulsant activity of valproic acid. AB - The unequivocal hypotheses about anticonvulsant activity of valproic acid (VPA) have always been a basic hurdle in designing next generation neurotherapeutics, particularly the anti-epileptic drugs. The present study reports about a comprehensive in-silico investigation into qualitative and quantitative binding of VPA and corresponding natural ligands of four major enzymes involved in neurotransmissions, namely-GABA transaminase (GABAt), alpha-keto glutarate dehydrogenase (alpha-KGDH), Succinate Semialdehyde dehydrogenase (SSADH) and Glutamate Decarboxylase (GAD), respectively. The molecular docking analyses revealed that VPA inhibits GABAt and alpha-KGDH through allosteric while SSADH through competitive mode of binding. There is an observed elevation in binding of glutamate over GAD in the presence of VPA. The docking inhibition constant (Ki) of VPA to all the studied enzymatic receptors were observed to be well below the therapeutic concentration of VPA in blood, except for alpha-KGDH, thus favouring GABAergic over glutamatergic mode of anticonvulsant activity of VPA. The report is probably the first comprehensive in-silico molecular study about VPA action. PMID- 27261620 TI - Clozapine and olanzapine are better antioxidants than haloperidol, quetiapine, risperidone and ziprasidone in in vitro models. AB - Although the etiopathogenic mechanisms of schizophrenia (SCZ) are unknown, evidences suggest that excessive free radical production or oxidative stress may be involved in the pathophysiology of SCZ. Antipsychotics are the drugs used in the treatment of SCZ but it remains controversial the impact that typical vs. atypical antipsychotics has on the oxidative stress status in SCZ patients. In vitro, the antioxidant capacity of six antipsychotics was assessed by their ability to: decrease or scavenge reactive oxygen species in the neutrophil respiratory burst; donate hydrogen and stabilize the free radical 2,2-diphenyl-1 picryl-hydrazyl (DPPH); and scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6 sulphonic acid) (ABTS(+)). This study demonstrated that both clozapine and olanzapine have antioxidant effects, in vitro, by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS(+) assay and stabilizing the radical DPPH. Ziprasidone significantly scavenged ABTS(+) and stabilized the radical DPPH whereas risperidone significantly reduced the respiratory burst. Haloperidol and quetiapine lacked antioxidant effects. The chemical structure related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs on the top of their antipsychotic mechanism of action. PMID- 27261621 TI - Cissus quadrangularis prevented the ovariectomy induced oxidative stress in the femur of adult albino rats. AB - The increasing evidence suggesting the role of free radicals in bone resorption and bone loss prompted us to explore whether the consumption of antioxidant rich medicinal plant C. quadrangularis modifies antioxidant status in ovariectomized rats. METHODS: Twenty four female adult rats, 90days old showing regular estrous cycles were used for the present study. The animals were divided into two groups. The Group-1 rats (n=6) were sham operated and Group-II rats were bilaterally ovariectomized (n=18) and treated with C. quadrangularis for sixty days (100mg/kg body weight and 250mg/kg body weight). After sixty days, the rats were killed, femora were dissected out, minced and homogenized in Tris-HCl buffer (pH 7.4) and the supernatant was collected and used for biochemical assays. RESULTS: Ovariectomy registered a decrease (p<0.05) in the activities of SOD, GPx, GST, ALP, collagen content and increased (p<0.05) the activities of TRAP and lipid peroxidation. Simultaneous administration of C. quadrangularis maintained the enzyme activities in ovariectomized rats. CONCLUSION: C. quadrangularis, a natural herb may be used to treat the estrogen deficiency/menopause onset and ovariectomy induced oxidative stress. PMID- 27261622 TI - Anti-inflammatory effect of taurocholate on TNBS-induced ulcerative colitis in mice. AB - Taurocholate is a natural conjugated bile acid. The aim of this study was to evaluate the anti-inflammatory effect of taurocholate in TNBS-induced ulcerative colitis in mice. The colitis were induced by rectal administration of TNBS. After 24h, the experimental animals were treated with sulfasalazine (SASP, 500mg/kg/day) and taurocholate (20, 40 and 60mg/kg) for 7 consecutive days. The anti-inflammatory effects of taurocholate for colitis were assessed by body weight, colonic weight and length, macroscopic scores, and histopathological examinations. In addition, the colonic tissue levels of myeloperoxidase (MPO) activity, interleukin (IL)-1beta, interferon (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were also determined to assess the effect of taurocholate. Compared with the model group, treatment with taurocholate (20, 40 and 60mg/kg) significantly inhibited the body weight loss, improved colonic weight and length, and decreased macroscopic and histopathological scores. Furthermore, the activity accumulation of MPO and the colonic tissue levels of IL 1beta, IFN-gamma and TNF-alpha were also decreased by administration of taurocholate. All the findings of this study suggested that taurocholate has the anti-inflammatory effect in ulcerative colitis in mice and indicated it as a good candidate to treat inflammatory bowel disease. PMID- 27261623 TI - miR-663a inhibits hepatocellular carcinoma cell proliferation and invasion by targeting HMGA2. AB - Hepatocellular carcinoma (HCC) is a highly aggressive solid malignancy throughout the world. Dysregulation of miRNAs play essential roles in HCC progression via aberrant regulation of cell proliferation, apoptosis, as well as metastasis. miR 663a is a poorly investigated miRNA. Whether miR-663a regulates HCC development remains unknown. The aim of the study was to explore the role of miR-663a in HCC development. To determine the expression level of miR-663a in HCC, we analyzed the data from GSE21362 and TCGA. The results showed that miR-663a was significantly down-regulated in HCC tissue compared with adjacent non-tumor tissue. Gain of function and loss of function assays revealed that miR-663a distinctly inhibited cell proliferation, migration and invasion. Mechanistic investigations demonstrated that miR-663a modulated cell functions through targeting and suppressing high mobility group A2 (HMGA2). In addition, overexpression of HMGA2 remarkably attenuated the tumor repressive effect of miR 663a. Taken together, miR-663a inhibits HCC cell proliferation and motility by targeting HMGA2. PMID- 27261624 TI - Protective effect of aqueous seed extract of Vitis Vinifera against oxidative stress, inflammation and apoptosis in the pancreas of adult male rats with diabetes mellitus. AB - INTRODUCTION: Protective effects of Vitis Vinifera seed aqueous extract (VVSAE) against pancreatic dysfunctions and elevation of oxidative stress, inflammation and apoptosis in the pancreas in diabetes were investigated. Histopathological changes in the pancreas were examined under light microscope. METHODS: Blood and pancreas were collected from adult male diabetic rats receiving 28days treatment with VVSAE orally. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin and lipid profile levels and activity levels of anti-oxidative enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) in the pancreas were determined by biochemical assays. Histopathological changes in the pancreas were examined under light microscopy and levels of insulin, glucose transporter (GLUT)-2, tumor necrosis factor (TNF)-alpha, Ikkbeta and caspase-3 mRNA and protein were analyzed by real-time PCR (qPCR) and immunohistochemistry respectively. Radical scavenging activity of VVSAE was evaluated by in-vitro anti oxidant assay while gas chromatography-mass spectrometry (GC-MS) was used to identify the major compounds in the extract. RESULTS: GC-MS analyses indicated the presence of compounds that might exert anti-oxidative, anti-inflammatory and anti-apoptosis effects. Near normal FBG, HbAIc, lipid profile and serum insulin levels with lesser signs of pancreatic destruction were observed following administration of VVSAE to diabetic rats. Higher insulin, GLUT-2, SOD, CAT and GPx levels but lower TNF-alpha, Ikkbeta and caspase-3 levels were also observed in the pancreas of VVSAE-treated diabetic rats (p<0.05 compared to non-treated diabetic rats). The extract possesses high in-vitro radical scavenging activities. CONCLUSION: In conclusions, administration of VVSAE to diabetic rats could help to protect the pancreas against oxidative stress, inflammation and apoptosis-induced damage while preserving pancreatic function near normal in diabetes. PMID- 27261625 TI - RETRACTED: Twist2 promotes kidney cancer cell proliferation and invasion via regulating ITGA6 and CD44 expression in the ECM-Receptor-Interaction pathway. AB - Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence proves that Twist2 involves in tumor progression; however, the role of Twist2 in human kidney cancer and its underlying mechanisms remain unclear. RT-PCR and Western blot analysis were used to detect the expression of Twist2 in kidney cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration and invasion assay was measured by the Cell Count Kit-8 (CCK8), flow cytometry, wound healing and transwell analysis, respectively. Gene set enrichment analysis (GSEA) was used to identify correlation of Twist2 with ECM-Receptor-Interaction pathway. In this report, we show that Twist2 up-regulated in human kidney cancer tissues compared with normal kidney tissues. Twist2 promotes cell proliferation, inhibits cell apoptosis, augments cell migration and invasion in human kidney cancer-derived cell in vitro, and promotes tumor growth in vivo. Moreover, we found that knockdown of Twist2 decreased the levels of ITGA6 and CD44 which contribute to cell migration and invasion correlated with ECM-Receptor-Interaction pathway. This result indicates Twist2 may promote migration and invasion of kidney cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 involves in kidney cancer progression. The identification of the role Twist2 on the migration and invasion of kidney cancer provides a potential appropriate treatment after radical nephrectomy to get a better prognosis that reducing recurrence. PMID- 27261626 TI - Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells. AB - In this study, we investigated the antitumor activity of Silymarin in a mouse model of colon cancer xenograft of Lewis lung cancer (LLC) cells. Silymarin significantly suppressed tumor growth and induced apoptosis of cells in tumor tissues at a dose of 25 and 50mg/kg. Silymarin treatment enhanced the infiltration and function of CD8(+) T cells. In the meantime, Silymarin decreased the level of IL-10 while elevated the level of IL-2 and IFN-gamma in the serum of tumor-bearing mice. Finally, Silymarin reduced the proportion of myeloid-derived suppressor cells (MDSC) in the tumor tissue and also the mRNA expressions of inducible nitric oxide synthases-2 (iNOS2), arginase-1 (Arg-1) and MMP9, which indicated that the function of MDSC in tumor tissues were suppressed. Altogether, our data here showed that Silymarin inhibited the MDSC and promoted the infiltration and function of CD8(+) T cells thus suppressed the growth of LLC xenografts, which provides evidence for the possible use of Silymarin against lung cancer. PMID- 27261627 TI - Anti-atherosclerosis effect of different doses of CETP vaccine in rabbit model of atherosclerosis. AB - AIM: To evaluate atheroprotective effects of different doses of cholesteryl ester transfer protein (CETP) vaccine, three doses of Tetanus toxoid-CETP (TT-CETP) peptide including 10, 50 and 100/rabbit, termed FA10, FA50, FA100, respectively, were administered in rabbit model of atherosclerosis. METHODS: Animals were vaccinated subcutaneously (S.C.) with 100MUl of vaccine in presence of complete Freund's adjuvant (CFA) for the first administration. Rabbits were boosted 4 times at 3 weeks intervals with the same peptide dose formulated in incomplete Freund's adjuvant (IFA). Animals were fed with diet supplemented with 2% cholesterol from week 11 to week 19. Anti-TT-CETP specific antibody and CETP activity in sera were determined. Therapeutic response was examined by tracking plasma lipoprotein levels (HDL-C, LDL-C and total cholesterol), and pathologic observation of intima/media thickness at the site of aortic lesions. RESULTS: All TT-CETP vaccine doses generated strong anti TT-CETP antibody response. CETP activity reduced in rabbits vaccinated with FA100 (P=0.031). FA100 showed significant increase in level of HDL-C rather than control group (P=0.006). However, no significant reduction were found in atherosclerotic lesion when compared to control. CONCLUSION: Inhibition of CETP activity and increased HDL-C were found with FA100, but the vaccine failed to prevent aortic lesion development in immunized rabbits when compared to control. Our result supports the hypothesis stated that CETP may not be an attractive therapeutic target for the prevention of cardiovascular disease. PMID- 27261628 TI - Obestatin attenuated doxorubicin-induced cardiomyopathy via enhancing long noncoding Mhrt RNA expression. AB - OBJECTIVE: The emergence of side-effect of doxorubicin in cardiomyopathy and heart failure has led to the search for diverse strategies to prevent its cytotoxic effects. This study was to determine the role of obestatin on doxorubicin-induced cardiomyocytes apoptosis and possible underlying mechanism. METHODS: Sprague Dawley rats were divided into 3 groups and received treatment for a total of 6 weeks: group1, untreated normal rats; group2, Doxorubicin induced heart cardiomyopathy (DC) rats; and group3, obestatin treated HC rats. Doxorubicin (2.5mg/kg) or obestatin (100MUg/kg/d) were discontinuously administered via intraperitoneal injection. Primary cardiomyocytes and H9C2 cell line were used for in vitro experiments. Mhrt and Nrf2 (nuclear factor erythroid 2 -related factor 2) mRNA expressions were determined using qRT-PCR. Expression of Nrf2 protein was determined using western blotting. TUNEL assay was performed to evaluate cell apoptosis. RESULTS: Administration of obestatin significantly improved doxorubicin-induced dysfunction of left ventricular contractility function, moreover, resulted in upregulation of Mhrt and Nrf2 in failing myocardial tissue. Co-incubation of obestatin and doxorubicin in primary cardiomyocytes also enhanced Mhrt and Nrf2 expression as well as prevented cell apoptosis in comparison with doxorubicin only. Manipulation of cellular Mhrt by pcDNA-Mhrt or si-Mhrt transfection positively regulated Nrf2 expression in doxorubicin-incubated cardiomyocytes. Silencing Mhrt reversed cardioprotective effects of obestatin both in vivo and in vitro. CONCLUSION: Administration of obestatin attenuates doxorubicin-induced cardiac dysfunction via preservation of cardiomyocytes apoptosis in a Mhrt-Nrf2 dependent pathway. PMID- 27261629 TI - A novel small-molecule YLT256 inhibits proliferation and induces apoptosis both in vitro and in vivo in solid tumors. AB - Pancreatic carcinoma is a still unsolved health problem all over the world with poor prognosis and high mortality rate. YLT256, a novel synthesized chemical small inhibitor, displays potent antineoplastic activities via inducing apoptosis both in vitro and in vivo. In this study, we found that YLT256 showed growth inhibition against a broad spectrum of human cancer cell lines and pancreatic cancer cell line BxPc-3 was the most sensitive with an IC50 of 0.42MUM. We also found YLT256 could induce apoptosis of BxPc-3 cells in a dose-dependent manner. Western blot analysis revealed that the occurrence of its apoptosis was associated with activation of caspases-3 and -9, up-regulation of pro-apoptotic Bak, and down-regulation of anti-apoptotic Bcl-2. Moreover, YLT256-treated resulted in changes of mitochondrial membrane potential (Deltapsim), and generation of reactive oxygen species (ROS). Furthermore, our data also revealed that YLT256 suppressed the growth of established tumor-bearing xenograft models without obvious side effects. Immunohistochemical analyses and TUNEL assay revealed an increase in cleaved caspase-3-positive cells and TUNEL-positive cells, a decrease in Ki67-positive cells upon YLT256. Together, all the results of present study provided evidence demonstrating that YLT256 could be a promising potential drug candidate for pancreatic cancer therapy. PMID- 27261630 TI - Tangeretin induces cell cycle arrest and apoptosis through upregulation of PTEN expression in glioma cells. AB - Tangeretin (TANG), present in peel of citrus fruits, has been shown to various medicinal properties such as chemopreventive and neuroprotective. However, the chemopreventive effect of TANG on glioblastoma cells has not been examined. The present study was designed to explore the anticancer potential of TANG in glioblastoma cells and to investigate the related mechanism. Human glioblastoma U 87MG and LN-18 cells were treated with 45MUM concentration of TANG and cell growth was measured by MTT assay. The cell cycle distribution and cell death were measured by flow cytometry. The expression of cell cycle and apoptosis related genes were analyzed by quantitative RT-PCR and western blot. The cells treated with TANG were significantly increased cell growth suppression and cell death effects than vehicle treated cells. Further, TANG treatment increases G2/M arrest and apoptosis by modulating PTEN and cell-cycle regulated genes such as cyclin-D and cdc-2 mRNA and protein expressions. Moreover, the ability of TANG to decrease cell growth and to induce cell death was compromised when PTEN was knockdown by siRNA. Taken together, the chemopreventive effect of TANG is associated with regulation of cell-cycle and apoptosis in glioblastoma, thereby attenuating glioblastoma cell growth. Hence, the present findings suggest that TANG may be a therapeutic agent for glioblastoma treatment. PMID- 27261632 TI - Giant Meckel's diverticulum torsion that mimics adnexal pathology. AB - Meckel's diverticulum is a real diverticulum located at the antimesenteric portion of intestinal loops and including all layers of the intestinal wall. It is the most common congenital anomaly of the gastrointestinal tract, and its incidence is 1-3%. Many asymptomatic cases are diagnosed when complications occur. A 23-year-old female patient applied to gynaecology emergency clinic with pelvic pain complaint. Laparotomy was performed with the diagnosis of acute abdomen because the physical examination and imaging studies did not exclude tuboovary pathology. Giant Meckel's diverticulitis and ischemic bowel loops that had been torsion were observed. Obstruction is the most common complication and generally originates from inflammation, adhesions, intussusception and omphalo mesenteric band. In this case, it was seen that mobilized diverticulitis can be complicated without any fibrous band or adhesion to adjacent organs. This case supports that there can be torsion of bowel in free Meckel's diverticulum. Meckel's diverticulum settled in the pelvic region can make a clinical manifestation that is difficult to distinguish from adnexal diseases. It should be kept in mind for cases that start with pelvic pain, form adnexal pathology suspicion and cause an acute abdomen. PMID- 27261631 TI - Post-cocaine changes in regulator of G-protein signaling (RGS) proteins in the dorsal striatum: Relevance for cocaine-seeking and protein kinase C-mediated phosphorylation. AB - Persistent cocaine-induced neuroadaptations within the cortico-striatal circuitry might be related to elevated risk of relapse observed in human addicts even after months or years of drug-free abstinence. Identification of these neuroadaptations may lead development of novel, neurobiologically-based treatments of relapse. In the current study, 12 adult male Sprague-Dawley rats self-administered cocaine (or received yoked-saline) for two weeks followed by three weeks of home-cage abstinence. At this point, we analyzed expression of proteins involved in regulation of Galphai- and Galphaq-protein signaling in the dorsal striatum (dSTR). Animals abstinent from chronic cocaine showed decreased expression of regulator of G-protein signaling 2 (RGS2) and RGS4, as well as upregulation of RGS9. These data, together with the increased ratio of Galphaq-to-Galphai proteins indicated, "sensitized" Galphaq signaling in the dSTR of abstinent cocaine animals. To evaluate activation of Galphaq signaling during relapse, another group of abstinent cocaine animals (and yoked saline controls, 22 rats together) was reintroduced to the cocaine context and PKC-mediated phosphorylation in the dSTR was analyzed. Re-exposure to the cocaine context triggered cocaine seeking and increase in phosphorylation of cellular PKC substrates, including phospho-ERK and phospho-CREB. In conclusion, this study demonstrates persistent dysregulation of RGS proteins in the dSTR of abstinent cocaine animals that may produce an imbalance in local Galphaq-to-Galphai signaling. This imbalance might be related to augmented PKC-mediated phosphorylation during relapse to cocaine-seeking. Future studies will address whether selective targeting of RGS proteins in the dSTR can be utilized to suppress PKC-mediated phosphorylation and relapse to cocaine-seeking. PMID- 27261633 TI - Computer tomography navigation for the transoral anterior release of a complex craniovertebral junction deformity: A report of two cases. AB - INTRODUCTION: The surgical correction of deformities of the craniovertebral junction (CVJ) remains a challenge due to its complex anatomy. Despite the well known usefulness of computed tomography (CT) navigation in posterior spinal surgery, it is applied far less frequently in anterior spinal surgery, mainly due to registration difficulties. PRESENTATION OF THE CASE: Case 1 was a 68-year-old female with rheumatoid arthritis, with a complaint of neck pain, motor weakness, and dysesthesia in the upper extremities. Case 2 was a 61-year-old male with Chiari malformation, with a complaint of neck pain and gait disturbance after a fall. Magnetic resonance imaging (MRI) showed severe atlantoaxial dislocation and multilevel cervical spinal cord compression in both patients. Continuous halo traction failed to reduce atlantoaxial dislocation, even under general anesthesia, and they were treated with combined anterior release and posterior decompression and fixation using CT navigation. Occipitocervical assimilation, which was present in both patients, enabled precise registration for navigation. DISCUSSION: The lack of anatomically characteristic landmarks on the vertebral surface makes obtaining accurate registration difficult in anterior CVJ surgery using CT navigation. The remaining mobility in the occipitocervical joint precludes the use of facial or cranial landmarks. However, occipitocervical assimilation, which is not uncommon in patients with CVJ deformities, enables accurate navigation during transoral surgery. CONCLUSION: Transoral anterior release using CT navigation is an effective treatment option for rigid complex CVJ deformities. The accurate identification of the patients' anatomical features such as occipitoatlantal assimilation, is crucial for the conducting accurate preoperative CT-based navigation during transoral surgery. PMID- 27261634 TI - Residential buffer, perceived neighborhood, and individual activity space: New refinements in the definition of exposure areas - The RECORD Cohort Study. AB - Neighborhood effects on health have been widely investigated; yet the definition of neighborhoods is usually arbitrary. This study analyses how disparities in environmental exposure according to urbanicity vary when considering a home centered network-buffer, the perceived residential neighborhood, or the activity space. Exposures to the density of destinations and proportion of green space were compared for three spatial definitions of exposure areas, overall and stratified by urbanicity of the residence. Environmental exposure levels and gradients by urbanicity were found to vary depending on the spatial definition of the exposure area. PMID- 27261635 TI - Census tract correlates of vape shop locations in New Jersey. AB - INTRODUCTION: Vape shops are opening across the USA, but little is known about the types of neighborhoods where they are located. This study explores community level predictors of vape shop locations in New Jersey, USA. METHODS: Vape shops were identified in July 2015 using a validated systematic online search protocol and geocoded using Google Earth Pro. Multivariable logistic regression identified demographic and other predictors of vape shop presence at the census tract level. RESULTS: Tobacco outlet density was consistently associated with higher odds of vape shop presence after adjusting for covariates (p<0.05). However, factors traditionally associated with tobacco retail were negatively associated with vapor outlets. Census tracts with a higher proportion of non-Hispanic black residents had significantly lower odds of having a vape shop (beta=-0.03, p<0.001). DISCUSSION: Vape shops are commonly located in census tracts where tobacco retail is high, but where fewer racial minorities live. The retail environment may communicate social norms regarding vaping and ultimately influence use behaviors of community residents. PMID- 27261636 TI - Prototype End-of-Life Quality Measures Based on MDS 3 Data. AB - BACKGROUND: The Nursing Home Compare (NHC) report card does not include end-of life (EOL) quality measures (QMs). OBJECTIVES: To develop and examine the properties of EOL QMs. SUBJECTS: A total of 39,590 nursing home decedents in 626 facilities in New York State in fiscal year 2012. DESIGN: Statistical analyses of Minimum Data Set 3 data, including multivariable regression analyses and descriptive statistics. MEASURES: Death in the hospital, number of hospitalizations, pain, and depression during the last 90 days before death. RESULTS: Overall, 32% of residents died in the hospital. They averaged 0.49 hospitalizations in the last 90 days before death, 10% reported moderate to severe pain, and 17% had depressive symptoms. The EOL QMs exhibited variation across facilities similar to that observed for other QMs. They showed low or moderate correlations. The pain and depression QMs were significantly better among nursing homes ranked by NHC as 4 and 5 stars compared with those ranked as 1 and 2 stars for most dimensions. The hospitalizations QMs were significantly better among nursing homes ranked by NHC as 4 and 5 stars compared with those ranked as 1 and 2 stars only when compared on the staffing dimension. CONCLUSIONS: The Minimum Data Set 3 includes much information that can be used to assess quality of EOL care in nursing homes. The prototype measures we developed could be improved if information about advance directives and the nonclinical aspects of care, such as comfort and emotional support for both the resident and the family and respect for resident and family preferences, were collected. PMID- 27261637 TI - Hospital Phenotypes in the Management of Patients Admitted for Acute Myocardial Infarction. AB - OBJECTIVES: To characterize hospital phenotypes by their combined utilization pattern of percutaneous coronary interventions (PCI), coronary artery bypass grafting (CABG) procedures, and intensive care unit (ICU) admissions for patients hospitalized for acute myocardial infarction (AMI). RESEARCH DESIGN: Using the Premier Analytical Database, we identified 129,138 hospitalizations for AMI from 246 hospitals with the capacity for performing open-heart surgery during 2010 2013. We calculated year-specific, risk-standardized estimates of PCI procedure rates, CABG procedure rates, and ICU admission rates for each hospital, adjusting for patient clinical characteristics and within-hospital correlation of patients. We used a mixture modeling approach to identify groups of hospitals (ie, hospital phenotypes) that exhibit distinct longitudinal patterns of risk-standardized PCI, CABG, and ICU admission rates. RESULTS: We identified 3 distinct phenotypes among the 246 hospitals: (1) high PCI-low CABG-high ICU admission (39.2% of the hospitals), (2) high PCI-low CABG-low ICU admission (30.5%), and (3) low PCI-high CABG-moderate ICU admission (30.4%). Hospitals in the high PCI-low CABG-high ICU admission phenotype had significantly higher risk-standardized in-hospital costs and 30-day risk-standardized payment yet similar risk-standardized mortality and readmission rates compared with hospitals in the low PCI-high CABG-moderate ICU admission phenotype. Hospitals in these phenotypes differed by geographic region. CONCLUSIONS: Hospitals differ in how they manage patients hospitalized for AMI. Their distinctive practice patterns suggest that some hospital phenotypes may be more successful in producing good outcomes at lower cost. PMID- 27261639 TI - Measuring Health-related Quality of Life in Teens With and Without Depression. AB - PURPOSE: To provide empirical evidence on the performance of common measures in assessing health-related quality of life (HRQL) in depressed and nondepressed youth. These measures can be used in research trials, cost-effectiveness studies, and to help develop policy for treating youth depression. BACKGROUND: Depression is one of the most common mental disorders among adolescents, with a chronic, episodic course marked by considerable impairment. Data on HRQL for teens with depression could more fully demonstrate the burden of depression and help to evaluate the comparative effectiveness of teen depression services, which in turn can be used to inform public and clinical policies. METHODS: We collected data on depression and HRQL from 392 depressed and nondepressed teens aged 13-17. RESULTS: Generic mental health, disease-specific, and generic preference-based measures of HRQL all do a reasonable job of distinguishing teens with and without depression and between teens with differing levels of depression. Generic mental health and disease-specific measures provide valuable information on burden of disease and perform well. For the purpose of economic evaluation, the HUI-3 and EQ-5D perform somewhat better than other preference-based measures. These results can aid future research on teens with depression by helping to guide which HRQL instruments are most useful in this population and can help to quantify the burden of depression in teens for policy and clinical planning. PMID- 27261638 TI - Massachusetts Health Reform's Effect on Hospitals' Racial Mix of Patients and on Patients' Use of Safety-net Hospitals. AB - BACKGROUND: Because of residential segregation and a lack of health insurance, minorities often receive care in different facilities than whites. Massachusetts (MA) health reform provided insurance to previously uninsured patients, which enabled them to potentially shift inpatient care to nonminority-serving or nonsafety-net hospitals. OBJECTIVES: Examine whether MA health reform affected hospitals' racial mix of patients, and individual patients' use of safety-net hospitals. RESEARCH DESIGN: Difference-in-differences analysis of 2004-2009 inpatient discharge data from MA, compared with New York (NY), and New Jersey (NJ), to identify postreform changes, adjusting for secular changes. SUBJECTS: (1) Hospital-level analysis (discharges): 345 MA, NY, and NJ hospitals; (2) patient-level analysis (patients): 39,921 patients with >=2 hospitalizations at a safety-net hospital in the prereform period. MEASURES: Prereform to postreform changes in percentage of discharges that are minority (black and Hispanic) at minority-serving hospitals; adjusted odds of patient movement from safety-net hospitals (prereform) to nonsafety-net hospitals (postreform) by age group and state. RESULTS: Treating NJ as the comparison state, MA reform was associated with an increase of 5.8% (95% CI, 1.4%-10.3%) in the percentage of minority discharges at MA minority-serving hospitals; with NY as the comparison state, the change was 2.1% (95% CI, -0.04% to 4.3%). Patient movement from safety-net to nonsafety-net hospitals was greater in MA than comparison states (difference-in differences adjusted OR=1.3; 95% CI, 1.0-1.7; P=0.04). CONCLUSIONS: Following MA health reform, the safety-net remains an important component of the health care system. PMID- 27261641 TI - Comparison of Long-run Trends in 30-day Readmission by Degrees of Medicare Payment Cuts. AB - BACKGROUND AND OBJECTIVE: The Affordable Care Act enacted significant Medicare payment reductions to providers, yet long-term effects of such major reductions on patient outcomes remain uncertain. Using the 1997 Balanced Budget Act (BBA) as an experiment, we compare long-run trends in 30-day readmission across hospitals with different amount of payment cuts. RESEARCH DESIGN, SUBJECTS, AND MEASURES: Using 100% Medicare claims between 1995 and 2011 and instrumental variable hospital fixed-effects regression models, we compared changes in 30-day readmission trends for 5 leading Medicare conditions between urban hospitals facing small, moderate, and large BBA payment reductions across 4 periods [1995 1997 (pre-BBA period), 1998-2000, 2001-2005, 2006-2001]. Patient sample includes Medicare patients who were admitted to general, acute, urban, short-stay hospitals in the United States 1995-2011. Sample size ranges from 1.4 million patients for acute myocardial infarction to 3 million for pneumonia. RESULTS: We found that 30-day readmission trends diverged post-BBA (2001-2005) between hospitals facing small and large payment cuts, where large-cut hospitals experience slower improvement in readmission rates relative to small-cut hospitals. The gap between small-cut and large-cut hospitals readmission trend was 6% for acute myocardial infarction, 4% for congestive heart failure and pneumonia (all P<0.01) in the 2001-2005 period. The gaps between hospitals were eliminated by the 2006-2011 period as the effect of BBA naturally dissipated over time. CONCLUSIONS: Although payment-cut differences are associated with widening gaps in readmission rates across hospitals, the negative association appears to dissipate in the long run. PMID- 27261640 TI - The Effects of the Transition From Medicaid to Medicare on Health Care Use for Adults With Mental Illness. AB - BACKGROUND: The transition from Medicaid-only to dual Medicare/Medicaid coverage has the potential to reduce financial barriers to health care for patients with serious mental illness through increased coverage or expanded access to clinicians as their reimbursement increases. AIMS: To estimate the effect of dual coverage after Medicaid enrollment during the required waiting period among adults with serious mental illness on health care use, overall and related to mental health and substance use disorders (MHSUD). METHODS: Data include enrollment and claims from Medicaid and Medicare in Missouri and South Carolina, from January 2004 to December 2007. We used an interrupted time-series design to estimate the effect of dual coverage on average use of outpatient, emergency department (ED), and inpatient care/month. RESULTS: After 12 months of dual coverage, the probability of outpatient care use increased in both states from 4% to 9%. In Missouri, the mean probability and frequency of ED visits, total and MHSUD related, increased by 21%-32%; the probability of all-cause and MHSUD related inpatient admissions increased by 10% and 19%, respectively. In South Carolina, the mean probability of any inpatient admission increased by 27% and of any MHSUD-related inpatient admission by 42%. DISCUSSION: The increase in use of outpatient care is consistent with the expected increase in coverage of, and payment for, outpatient services under dual coverage relative to Medicaid-only. Sustained increases in ED and inpatient admissions raise questions regarding the complexity of obtaining care under 2 programs, pent-up demand among beneficiaries pretransition, and the complementarity of outpatient and inpatient service use. PMID- 27261642 TI - Intraoperative ECoG During MRI-Guided Laser-Interstitial Thermal Therapy for Intractable Epilepsy. AB - MRI-guided laser-interstitial thermal therapy is a new modality for epilepsy surgery. In patients with intractable localization-related seizures, it has been used to ablate epileptogenic lesions with less morbidity than conventional craniotomies, and with potentially similar rates of seizure freedom. It is gaining favor in the treatment of mesial temporal sclerosis, in which the circumscribed epileptic focus is amenable to a stereotactic approach. In some centers, intraoperative electrocorticography (ECoG) is a standard procedure during tailored temporal lobectomies that include resection of mesial temporal structures. Results of intraoperative ECoG have been used to guide the extent of resection of mesial temporal structures and for prognostication. Given the limitations of burr-hole access during laser-interstitial thermal therapy, ECoG has not previously been applied. We present two case reports involving intraoperative ECoG monitoring with a depth electrode placed into the parahippocampal region, with recording before and immediately after thermal ablation of the mesial temporal region. In each case, there were decreases in the mesial temporal spike activity after laser ablation of the hippocampus. This is the first demonstration of intraoperative neurophysiologic motoring during laser interstitial thermal therapy. The role of intraoperative ECoG for guiding the extent of ablation and determining prognosis during MRI-guided laser-interstitial thermal therapy remains to be determined. PMID- 27261643 TI - Neonatal EEG: An Update. PMID- 27261644 TI - Description of PICU Unplanned Readmission. AB - OBJECTIVES: ICU readmission within 48 hours of discharge is associated with increased mortality. The objectives of this study were to describe the frequency of, factors associated with, and outcomes associated with unplanned PICU readmission. DESIGN: A retrospective case-control study was performed. We evaluated 13 candidate risk factors and report patient outcomes following readmission. Subgroup analyses were performed for patients discharged from the cardiac PICU and medical-surgical PICU. SETTING: The study was undertaken at the Hospital for Sick Children, Department of Critical Care Medicine. PATIENTS: Eligible patients were discharged from the PICU to an inpatient ward between December 2006 and January 2013. Case patients were readmitted to the PICU within 48 hours of discharge. MEASUREMENTS AND MAIN RESULTS: There were 10,422 eligible patient discharges; 264 (2.5%) were readmitted within 48 hours. In the univariable analysis, unplanned readmission was associated with PICU patient admissions of younger age, lower weight, greater duration of PICU stay, greater cumulative stay in PICU in the past 2 years, higher Pediatric Logistic Organ Dysfunction score on PICU discharge, discharge outside goal discharge time (06:00 11:59 hr), use of extracorporeal organ support during ICU stay, greater Bedside Pediatric Early Warning Score, at discharge and discharge from the cardiac PICU. In the multivariable analysis, the factors most significantly associated with unplanned PICU readmission were length of stay more than 48 hours, greater cumulative length of PICU stay in the past 2 years, discharge from cardiac PICU, and higher Pediatric Logistic Organ Dysfunction and Bedside Pediatric Early Warning Scores on index discharge. Mortality was 1.8 times (p = 0.03) higher in patients with an unplanned PICU readmission compared with patients during their index PICU admission. CONCLUSIONS: The only potentially modifiable factors we found associated with PICU readmission within 48 hours of discharge were discharge time of day and the Pediatric Logistic Organ Dysfunction and Bedside Pediatric Early Warning Scores at the time of PICU discharge. PMID- 27261645 TI - Volume-Outcome Relationships in Pediatric Intensive Care. PMID- 27261646 TI - Patient-Centered Communication in the PICU: Where, When, and How. PMID- 27261647 TI - Does Telemedicine Really Improve the Status of Critically Ill Children? PMID- 27261648 TI - Sepsis Care Differences Unlike Beauty Are Not Skin Deep. PMID- 27261649 TI - Predicting the Outcome of Congenital Diaphragmatic Hernia in a SNAP (Score for Neonatal Acute Physiology). PMID- 27261650 TI - Electroencephalographic Monitoring for Prognostication Following Cardiac Arrest: Ready for Prime Time? PMID- 27261651 TI - PICU Readmissions: Not Just Output but Patient Throughput. PMID- 27261652 TI - Caring for Long-Stay Critically Ill Children and Infants Refers Back to the Fundamentals of Patient- and Family-Centered Care. PMID- 27261653 TI - Outcomes After Pediatric Critical Illness: Important to Be Accurate. PMID- 27261654 TI - Less Is More-Revisiting Burn Resuscitation. PMID- 27261655 TI - Acute Kidney Injury in Newborns: The Evolution for Optimization of Diagnosis. PMID- 27261656 TI - The authors reply. PMID- 27261657 TI - Procalcitonin for Bacterial Infection Management: A Comprehensive Understanding May Clarify Its Due Value. PMID- 27261658 TI - The authors reply. PMID- 27261659 TI - Severity of Illness Confusion. PMID- 27261660 TI - The authors reply. PMID- 27261661 TI - What Is the Purpose of Using an Old Biomarker in the Prognosis in PICUs? PMID- 27261662 TI - The authors reply. PMID- 27261663 TI - Multiplex Tests in Critically Ill Children With Severe Lower Respiratory Tract Infections. PMID- 27261664 TI - Ventilator-Associated Infections Need a New Approach. PMID- 27261665 TI - Blood Volume, Plasma Volume, and RBC Volume in Polycythaemic Neonates After Palliative Congenital Heart Surgery. PMID- 27261666 TI - Who Fears Propofol Infusion in Children? The Actual Practice of Propofol Use in PICUs. PMID- 27261667 TI - The Challenges of Caring for Long-Stay Patients in the PICU. AB - OBJECTIVE: Compared to shorter-stay patients, caring for long-stay patients in the ICU entails a disproportionate burden for staff. Our objective was to gain a deeper understanding of the impact on staff of caring for children who have a prolonged stay on the PICU. DESIGN: Qualitative study based on semi-structured interviews. Data were analyzed using the Framework approach. SETTING: Children's tertiary hospital. PARTICIPANTS: Seventeen members of staff (7 psychosocial staff, 7 nurses, 3 consultants) working in the PICU, neonatal ICU, or cardiac ICU (PICU will be used to encompass neonatal ICU, cardiac ICU, and PICU for the remainder of this article). INTERVENTIONS: Semi-structured, tape-recorded interviews. MEASUREMENTS AND MAIN RESULTS: Staff reported both positive and challenging aspects of caring for long-stay patients in the PICU. Five key areas relating to the challenges of caring for long-stay patients were identified: staff expectations about their work, characteristics of the patient group, the impact on staff, the impact on the wider unit, and the availability of support. Staff views were often compounded by individual cases they had been involved with or had heard about which fell at either end of the spectrum of "good" and "bad". CONCLUSIONS: Whilst there are reported benefits associated with caring for long stay patients, there are a number of challenges reported that may have implications for staff and the wider unit. When caring for a particular sub-group of long-stay patients, staff may be more likely to experience negative impacts. A key priority for the PICU is to ensure that support mechanisms are timely, accessible, and allow staff to explore their own reactions to their work. PMID- 27261668 TI - Construct Validity and Responsiveness of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and Infant Scales in the PICU. AB - OBJECTIVES: To assess the construct validity and the responsiveness of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and Infant Scales in the medical-surgical (PICU) and cardiac PICU. DESIGN/SETTING/PARTICIPANTS: Prospective cohort study of 367 inpatients admitted either to the PICU or the cardiac ICU at Seattle Children's Hospital from January 2012 to June 2013. Parent/caregiver and child (>= 8 yr old, developmentally appropriate, and critical illness resolved) Pediatric Quality of Life Inventory scores were obtained within 24 hours of PICU/cardiac ICU discharge and subsequently at 4-12 weeks following hospital discharge. Of the 491 eligible participants invited to participate, 367 (74.7% response rate) completed the Pediatric Quality of Life Inventory survey at ICU discharge, and of these, 263 (71.7% follow-up response rate) completed the follow-up survey 4-12 weeks after hospital discharge. MEASUREMENTS AND MAIN RESULTS: Responsiveness was assessed by calculating improvement scores (difference between follow-up and ICU discharge scores, Delta Pediatric Quality of Life Inventory). Construct validity was examined by comparing mean improvement scores for known groups differing by medical complexity. At follow-up, [INCREMENT] Pediatric Quality of Life Inventory scores were as follows (mean +/- SD): physical domain, 34.8 +/- 32.0; and psychosocial domain, 23.1 +/- 23.5. Patients with complex chronic or noncomplex chronic disease had physical functioning improvement scores that were 17.4 points (95% CI, -28.3 to -6.5; p < 0.001) and 19.5 points (95% CI, -30.4 to -8.5; p < 0.002) lower than children with no chronic illness, respectively. Patients with complex chronic disease exhibited psychosocial improvement scores that were 9.6 points (95% CI, -18.4 to -0.8; p < 0.033) lower than patients without chronic disease. Patients with noncomplex chronic disease had similar psychosocial improvement scores when compared with patients without chronic disease. CONCLUSIONS: As a measure of health-related quality of live, Pediatric Quality of Life Inventory demonstrated responsiveness and construct validity in a broad population of critically ill children. This measure represents a patient-centered clinically meaningful patient-or-parent-reported outcome measure for pediatric research assessing the clinical effectiveness of PICU/cardiac ICU interventions. When using health-related quality of life recovery as an outcome measure to assess clinical effectiveness in the PICU/cardiac ICU setting, measuring and controlling for the level of medical complexity is important in order to understand the true impact of clinical interventions. PMID- 27261669 TI - Prescribe to Prevent: Overdose Prevention and Naloxone Rescue Kits for Prescribers and Pharmacists. AB - In March of 2015, the United States Department of Health and Human Services identified 3 priority areas to reduce opioid use disorders and overdose, which are as follows: opioid-prescribing practices; expanded use and distribution of naloxone; and expansion of medication-assisted treatment. In this narrative review of overdose prevention and the role of prescribers and pharmacists in distributing naloxone, we address these priority areas and present a clinical scenario within the review involving a pharmacist, a patient with chronic pain and anxiety, and a primary care physician. We also discuss current laws related to naloxone prescribing and dispensing. This review was adapted from the Prescribe to Prevent online continuing medical education module created for prescribers and pharmacists (http://www.opioidprescribing.com/naloxone_module_1 landing). PMID- 27261670 TI - Sativex Associated With Behavioral-Relapse Prevention Strategy as Treatment for Cannabis Dependence: A Case Series. AB - OBJECTIVES: Cannabis is the most commonly used illicit drug; a substantial minority of users develop dependence. The current lack of pharmacological treatments for cannabis dependence warrants the use of novel approaches and further investigation of promising pharmacotherapy. In this case series, we assessed the use of self-titrated dosages of Sativex (1:1, Delta tetrahydrocannabinol [THC]/cannabidiol [CBD] combination) and motivational enhancement therapy and cognitive behavioral therapy (MET/CBT) for the treatment of cannabis dependence among 5 treatment-seeking community-recruited cannabis dependent subjects. METHODS: Participants underwent a 3-month open-label self titration phase with Sativex (up to 113.4 of THC/105 mg of CBD) and weekly MET/CBT, with a 3-month follow-up. RESULTS: Sativex was well-tolerated by all participants (average dosage 77.5 THC/71.7 mg CBD). The combination of Sativex and MET/CBT reduced the amount of cannabis use and progressively reduced craving and withdrawal scores. THC/CBD metabolite concentration indicated reduced cannabis use and compliance with medication. CONCLUSIONS: In summary, this pilot study found that with Sativex in combination with MET/CBT reduced cannabis use while preventing increases in craving and withdrawal in the 4 participants completing the study. Further systematic exploration of Sativex as a pharmacological treatment option for cannabis dependence should be performed. PMID- 27261672 TI - Taxon interactions control the distributions of cryoconite bacteria colonizing a High Arctic ice cap. AB - Microbial colonization of glacial ice surfaces incurs feedbacks which affect the melting rate of the ice surface. Ecosystems formed as microbe-mineral aggregates termed cryoconite locally reduce ice surface albedo and represent foci of biodiversity and biogeochemical cycling. Consequently, greater understanding the ecological processes in the formation of functional cryoconite ecosystems upon glacier surfaces is sought. Here, we present the first bacterial biogeography of an ice cap, evaluating the respective roles of dispersal, environmental and biotic filtration occurring at local scales in the assembly of cryoconite microbiota. 16S rRNA gene amplicon semiconductor sequencing of cryoconite colonizing a Svalbard ice cap coupled with digital elevation modelling of physical parameters reveals the bacterial community is dominated by a ubiquitous core of generalist taxa, with evidence for a moderate pairwise distance-decay relationship. While geographic position and melt season duration are prominent among environmental predictors of community structure, the core population of taxa appears highly influential in structuring the bacterial community. Taxon co occurrence network analysis reveals a highly modular community structured by positive interactions with bottleneck taxa, predominantly Actinobacteria affiliated to isolates from soil humus. In contrast, the filamentous cyanobacterial taxon (assigned to Leptolyngbya/Phormidesmis pristleyi) which dominates the community and binds together granular cryoconite are poorly connected to other taxa. While our study targeted one ice cap, the prominent role of generalist core taxa with close environmental relatives across the global cryosphere indicate discrete roles for cosmopolitan Actinobacteria and Cyanobacteria as respective keystone taxa and ecosystem engineers of cryoconite ecosystems colonizing ice caps. PMID- 27261671 TI - Computational modeling of Repeat1 region of INI1/hSNF5: An evolutionary link with ubiquitin. AB - The structure of a protein can be very informative of its function. However, determining protein structures experimentally can often be very challenging. Computational methods have been used successfully in modeling structures with sufficient accuracy. Here we have used computational tools to predict the structure of an evolutionarily conserved and functionally significant domain of Integrase interactor (INI)1/hSNF5 protein. INI1 is a component of the chromatin remodeling SWI/SNF complex, a tumor suppressor and is involved in many protein protein interactions. It belongs to SNF5 family of proteins that contain two conserved repeat (Rpt) domains. Rpt1 domain of INI1 binds to HIV-1 Integrase, and acts as a dominant negative mutant to inhibit viral replication. Rpt1 domain also interacts with oncogene c-MYC and modulates its transcriptional activity. We carried out an ab initio modeling of a segment of INI1 protein containing the Rpt1 domain. The structural model suggested the presence of a compact and well defined betabetaalphaalpha topology as core structure in the Rpt1 domain of INI1. This topology in Rpt1 was similar to PFU domain of Phospholipase A2 Activating Protein, PLAA. Interestingly, PFU domain shares similarity with Ubiquitin and has ubiquitin binding activity. Because of the structural similarity between Rpt1 domain of INI1 and PFU domain of PLAA, we propose that Rpt1 domain of INI1 may participate in ubiquitin recognition or binding with ubiquitin or ubiquitin related proteins. This modeling study may shed light on the mode of interactions of Rpt1 domain of INI1 and is likely to facilitate future functional studies of INI1. PMID- 27261673 TI - Cotton (Gossypium hirsutum L.) boll rotting bacteria vectored by the brown stink bug, Euschistus servus (Say) (Hemiptera: Pentatomidae). AB - AIM: To determine the capacity of the brown stink bug (BSB) (Euschistus servus) to transmit an infective Pantoea agglomerans strain Sc 1-R into cotton (Gossypium hirsutum) bolls. METHODS AND RESULTS: A laboratory colony of BSB was maintained on fresh green beans. Either sterile or Sc 1-R contaminated beans were offered to adult insects. Strain Sc 1-R holds rifampicin resistance (Rif(r) ). Insects were then caged with unopened greenhouse-grown bolls. After 2 days, BSB were surface sterilized, ground, and then plated on media with and without Rif. Two weeks later, seed with lint were ground and plated on media with and without Rif. Microbes were recovered on nonselective media from all BSBs and from seed/lint at concentrations reaching 10(9) CFU g(-1) tissue. Rif(r) bacteria were recovered strictly from insects exposed to Sc1-R and from diseased seed/lint of respective bolls. CONCLUSIONS: Euschistus servus was capable of transmitting strain Sc 1-R into bolls resulting in disease. Insects not exposed to the pathogen deposited bacteria yet the nonpathogenic microbes produced insignificant damage to the boll tissue. SIGNIFICANCE AND IMPACT OF STUDY: This is the first study to concretely show the capacity of the BSB to transmit an infective P. agglomerans strain resulting in boll disease. PMID- 27261677 TI - Multiple Approaches to Multiple Sclerosis (and Other Demyelinating Diseases). PMID- 27261678 TI - New Approaches to the Diagnosis, Clinical Course, and Goals of Therapy in Multiple Sclerosis and Related Disorders. AB - The diagnosis, categorization, and treatment of multiple sclerosis (MS) and other demyelinating diseases have shifted over the past decade, and many of the fundamental principles of MS pathogenesis and clinical course are being rewritten. Fundamental issues include selecting the right disease-modifying therapy for someone with active disease and how, or even if, patients with purely progressive MS should be treated. This article provides an overview and introduction to the current thinking in MS diagnosis and therapy with an emphasis on the data-driven and proactive approach that has come to define the current state of the art. PMID- 27261679 TI - Incidental Lesions Suggesting Multiple Sclerosis. AB - PURPOSE OF REVIEW: Neurologists are frequently asked to consult on patients with incidentally observed anomalies on brain MRI that may be suggestive of multiple sclerosis (MS). The identification of such findings has important clinical management implications. This review provides an overview and practical clinical approach options for clinicians. RECENT FINDINGS: An increase in the number of brain MRI studies performed annually is expected to result in detection of a corresponding greater number of unanticipated anomalies. A disproportionate number of patients referred to neurologists for this reason have punctate subcortical T2 hyperintensities that appear nonspecific in origin rather than having imaging features concerning for MS. However, in some instances, the MRI characteristics appear to be typical for demyelination. When these features are observed, efforts should be pursued to identify an accurate explanation for the preclinical findings through rigorous clinical evaluation, paraclinical testing, and utilization of longitudinal imaging. SUMMARY: The identification of subjects with incidental T2 hyperintensities highly suggestive of MS is important for patient counseling and management. Continued neurologic evaluations and reassessment of the original clinical impression are recommended to ensure accurate interpretation of the available data. PMID- 27261680 TI - Early Relapsing Multiple Sclerosis. AB - PURPOSE OF REVIEW: This article provides an evidence-based approach to the management of patients with early relapsing multiple sclerosis (MS). RECENT FINDINGS: Numerous clinical trials have shown the role of disease-modifying therapies in reducing relapses and new MRI lesions in patients with relapsing MS. Many of these trials also show the ability of these agents to delay disability progression, and a few suggest that disease-modifying therapies may slow brain atrophy in relapsing MS; however, very few suggest that disease-modifying therapies can improve symptoms or disability. The therapeutic armamentarium of disease-modifying therapies includes five interferon formulations, two versions of glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, and alemtuzumab. SUMMARY: Although multiple disease-modifying therapies exist, the risks of these vary markedly, head-to-head comparator trials are limited, and no prospective biomarkers for treatment efficacy exist; therefore, choosing a disease-modifying therapy for an individual patient with MS is a difficult decision. This difficulty is compounded by limitations in predicting a patient's disease course, and the risk tolerance of the patient and opinions of the care partner need to be factored into the decision analysis as well. After a disease-modifying therapy is chosen, vigilance for clinical or radiographic breakthrough disease is very important, as this may suggest a suboptimal response to the chosen therapy. Furthermore, the role of symptom management and wellness should always remain part of the approach to the patient with MS. PMID- 27261681 TI - Severe, Highly Active, or Aggressive Multiple Sclerosis. AB - PURPOSE OF REVIEW: Despite the efficacy of current therapies for relapsing forms of multiple sclerosis (MS), there remains a group of patients whose disease fails to respond and warrants a different approach to treatment. This article reviews this form of aggressive MS and proposes a definition and new treatment algorithm. Failing to recognize aggressive MS and initiate more effective therapy will result in a lost opportunity to effectively treat the disease. RECENT FINDINGS: Natural history studies, together with the results of contemporary clinical trials, help to identify and profile a subset of patients with relapsing MS who have a much poorer prognosis and for whom conventional treatment tends to fail. Therapies that have shown success in the treatment of this patient group with aggressive MS are reviewed and discussed. SUMMARY: It is imperative to recognize aggressive MS to effectively treat it before patients progress. Recognizing aggressive MS as early as possible is the key to successful implementation of a proposed algorithm. PMID- 27261682 TI - Progressive Multiple Sclerosis. AB - PURPOSE OF REVIEW: Many therapeutic advances for relapsing-remitting multiple sclerosis (MS) have occurred in the past 25 years. Although similar advances in disease-modifying therapies have not been realized in progressive MS, many symptomatic therapeutic strategies can benefit patients with progressive MS. Few guidelines exist for management of patients with progressive MS. RECENT FINDINGS: The classification of progressive MS was revised in 2013 to include a description of inflammatory disease activity determined by clinical relapses or imaging findings. Developing knowledge about the pathogenesis of progressive MS and the role of comorbidities in modifying the disease course has implications for the clinical management of patients with progressive MS as well as for clinical trial design. Current and upcoming clinical trials will assess a wide range of interventions, including immunomodulatory agents, putative neuroprotective molecules, stem cell therapy, nutrition, and rehabilitation techniques. SUMMARY: None of the therapies currently approved for use in relapsing-remitting MS have been shown to slow the gradual progression of disability that occurs in the absence of recent relapses or changes in MRI. A multidisciplinary approach is needed to address the many symptoms that impact quality of life for patients with progressive MS. PMID- 27261683 TI - Acute Multiple Sclerosis Relapse. AB - PURPOSE OF REVIEW: This article discusses acute exacerbations (relapses) of multiple sclerosis (MS). Relapses are a hallmark of MS and are often associated with significant functional impairment and decreased quality of life. This review discusses the proposed pathophysiology of MS relapses, triggering factors, associated markers, variants of clinical presentation, and diagnostic recommendations. RECENT FINDINGS: Most MS exacerbations are followed by a period of repair leading to clinical remission; however, residual deficits may persist after MS relapse and contribute to the stepwise progression of disability. Treatment of MS relapses is important as it helps to shorten the duration of disability associated with their course. Successful treatment of relapse helps patients with MS obtain a vital sense of being able to gain control over the disease. Patients with relapsing MS who receive treatment report better outcomes than those who are simply observed. This article discusses treatment options for MS relapse, including systemic corticosteroids, adrenocorticotropic hormone, and plasma exchange. Recent findings related to the mechanisms of action of steroids and adrenocorticotropic hormone are also reviewed, and other potential therapies are assessed. A proposed algorithm for MS relapse management is presented, including strategies for steroid-resistant MS exacerbations. SUMMARY: MS relapses need to be recognized in a timely manner and treated using recommended therapeutic methods. PMID- 27261684 TI - Symptom Management and Lifestyle Modifications in Multiple Sclerosis. AB - PURPOSE OF REVIEW: This article reviews the rationale and approach to symptom management and lifestyle modifications in multiple sclerosis (MS). RECENT FINDINGS: MS symptoms are important to treat because they affect quality of life and daily activity. Appreciation of cluster symptoms (where one symptom contributes to another), changes over time, and multimodality therapeutic approaches are guiding optimized symptom management. Equally important are lifestyle modifications that enhance central nervous system reserve and function. These modifications are the foundation for a health maintenance, wellness, and vascular risk factor control program. SUMMARY: Symptom management and lifestyle modifications are important therapeutic targets to improve the lives of patients with MS. PMID- 27261685 TI - Pregnancy in the Setting of Multiple Sclerosis. AB - PURPOSE OF REVIEW: This article provides a review of the available data on reproductive issues that arise in patients with multiple sclerosis (MS). RECENT FINDINGS: Recent findings have replicated earlier findings that pregnancy and possibly breast-feeding bring about a favorable immunomodulatory effect in patients with MS. Use of disease-modifying therapies prior to pregnancy may further decrease a patient's risk for postpartum disease activity. SUMMARY: The annualized relapse rate in MS decreases during pregnancy, with a nadir in the third trimester, and rebounds significantly in the 3-month postpartum period. Exclusive breast-feeding may exert a beneficial effect in decreasing the postpartum risk for relapse. Certain assisted reproductive technology methods are thought to increase the risk for relapse. Disease-modifying therapies are generally discontinued during pregnancy and lactation with a few exceptions. The pregnancy course is usually routine without significant obstetric complications, and babies, although slightly smaller, are typically healthy. PMID- 27261686 TI - Switching or Discontinuing Disease-Modifying Therapies for Multiple Sclerosis. AB - PURPOSE OF REVIEW: This article reviews the reasons for discontinuation or switching of multiple sclerosis disease-modifying therapy as well as procedures that might mitigate risk to the patient under such circumstances. RECENT FINDINGS: Recent review of the literature, as well as the author's extensive clinical experience, indicate that the discontinuation of multiple sclerosis disease-modifying therapies occurs for many reasons. Often one medication is stopped at the recommendation of the physician in order to switch to another medication. However, often the decision to discontinue medication is made by the patient. Unfortunately, in still other situations, treatment is stopped because of circumstances beyond the control of either patient or physician (eg, a loss of insurance coverage). Currently available data do not permit a conclusion about whether it is ever safe to discontinue disease-modifying therapy in a stable patient without the expectation of return of disease activity. SUMMARY: Clinicians must help patients avoid unnecessary and undesirable cessation of disease-modifying therapy. While switches of therapy are often necessary, steps to minimize both adverse events and the risk of recurrent disease should be undertaken. Whether disease-modifying therapy can ever be purposely discontinued without incurring a significant risk of disease recurrence remains to be determined. PMID- 27261687 TI - Neuromyelitis Optica Spectrum Disorders. AB - PURPOSE OF REVIEW: This article provides a practical approach for providers caring for patients with neuromyelitis optica (NMO) spectrum disorders. Clinical and imaging features, diagnostic criteria, treatment of acute exacerbations, chronic preventive therapy, and symptom management in NMO spectrum disorders are discussed. RECENT FINDINGS: The rapid pace of research in NMO spectrum disorders has led to many recent advances. A broader understanding of the clinical spectrum of the disease as well as improvements in anti-aquaporin-4 antibody assays have led to recent revision of the diagnostic criteria. Several recent studies have expanded the knowledge base regarding the efficacy and safety of current therapies for NMO spectrum disorders. SUMMARY: An NMO spectrum disorder is an inflammatory disorder affecting the central nervous system, previously thought to be closely related to multiple sclerosis but more recently demonstrated to represent a distinct clinical and pathophysiologic entity. As NMO spectrum disorders carry significant morbidity and, at times, mortality, prompt and accurate diagnosis followed by swift initiation of therapy for both treatment of acute exacerbations and prevention of further relapses is critical. This article provides a practical approach to the diagnosis and management of NMO spectrum disorders. PMID- 27261688 TI - Pediatric Demyelination. AB - PURPOSE OF REVIEW: This review summarizes a general approach to pediatric demyelination as well as specific features of each of the acquired demyelinating syndromes to help clinicians in their evaluation of children with these disorders. Case studies are included to illustrate the expanding phenotype of many of these syndromes. RECENT FINDINGS: With the creation of consensus definitions for the pediatric acquired demyelinating syndromes, recognition of demyelination in children has increased, as has understanding of the clinical and radiologic features, prognosis, and response to treatment. Collaborative studies and multicenter clinical trials are ongoing and needed to appropriately evaluate emerging therapies for some of the chronic demyelinating disorders, such as multiple sclerosis and neuromyelitis optica (NMO) spectrum disorder. SUMMARY: This review will aid the clinician in identifying key features of the pediatric acquired demyelinating syndromes and highlights a general approach for the diagnosis and treatment of these disorders. PMID- 27261689 TI - Genetic Leukoencephalopathies in Adults. AB - PURPOSE OF REVIEW: More than 100 heritable disorders can present with abnormal white matter on neuroimaging. While acquired disorders remain a more common cause of leukoencephalopathy in the adult than genetic causes, the clinician must remain aware of features that suggest a possible genetic etiology. RECENT FINDINGS: The differential diagnosis of heritable white matter disorders in adults has been revolutionized by next-generation sequencing approaches and the recent identification of the molecular cause of a series of adult-onset disorders. SUMMARY: The identification of a heritable etiology of white matter disease will often have important prognostic and family counseling implications. It is thus important to be aware of the most common hereditary disorders of the white matter and to know how to distinguish them from acquired disorders and how to approach their diagnosis. PMID- 27261690 TI - Palliative Care in Multiple Sclerosis. AB - Collaboration between the neurologist and palliative care team in the care of patients with severe demyelinating disease can result in improved patient care, and discussion of the complex ethical issues that arise when a patient expresses a wish to die may be rewarding for both patients and caregivers. PMID- 27261691 TI - Health Literacy and Outcomes in Multiple Sclerosis. AB - Health literacy is an important consideration when managing patients with multiple sclerosis. Literacy impacts comprehension about patient condition, participation in medical decision making, and compliance with treatment plans. Awareness of health literacy allows clinicians to tailor their approach to individual patients and improve the overall care of patients. PMID- 27261692 TI - Coding in Multiple Sclerosis and Other Demyelinating Diseases. PMID- 27261696 TI - Patient Management Problem. PMID- 27261697 TI - Patient Management Problem-Preferred Responses. PMID- 27261699 TI - Review on the delivery of steroids by carrier proteins. AB - Due to the poor solubility of steroids in aqueous solution, delivery of these biomaterials is of major biomedical importance. We have reviewed the conjugation of testosterone and it aliphatic dimer and aromatic dimer with several carrier proteins, human serum albumin (HSA), bovine serum albumin (BSA) and milk beta lactoglobulin (b-LG) in aqueous solution at physiological pH. The results of multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were compared here. Steroid-protein bindings are via hydrophilic and H-bonding contacts. HSA forms more stable conjugate than BSA and b-LG. The stability of steroid-protein conjugates is testosterone>dimer aromatic>dimer-aliphatic. Encapsulation of steroids by protein is shown by TEM images. Modeling showed the presence of H-bonding, which stabilized testosterone protein complexes with the free binding energy of -12.95 for HSA and -11.55 for BSA and -8.92kcal/mol for b-LG conjugates. Steroid conjugation induced major perturbations of serum protein conformations. Serum proteins can transport steroids to the target molecules. PMID- 27261700 TI - Bacteriophytochromes control conjugation in Agrobacterium fabrum. AB - Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation. PMID- 27261701 TI - Phyto-mediated biosynthesis of silver nanoparticles using the rind extract of watermelon (Citrullus lanatus) under photo-catalyzed condition and investigation of its antibacterial, anticandidal and antioxidant efficacy. AB - The biological synthesis of nanoparticles has gained tremendous interest, and plants and plant extracts are preferred over other biological sources for this process because of their rich content of bioactive metabolites. In this study, silver nanoparticles (AgNPs) were produced utilizing the aqueous extract of watermelon rind (WRA), an agricultural waste material under photo exposed condition at room temperature, and tested for their antibacterial, anticandidal and antioxidant activities. The synthesized AgNPs showed surface plasmon resonance at 425nm with an average size of 109.97nm. The morphology and elemental composition was confirmed by scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). The Fourier transform infrared spectroscopy (FT IR) and thermogravimetric and differential thermogravimetric analysis (TG/DTG) confirmed that the bioactive compounds from the WRA extract were involved in the synthesis and capping of AgNPs. X-ray diffraction (XRD) revealed the crystallite nature of the AgNPs. The AgNPs exhibited strong broad spectrum antibacterial activity against five different foodborne bacteria with zones of inhibition 9.12 14.54mm in diameter. When AgNPs were mixed with kanamycin and rifampicin the mixture exhibited strong antibacterial synergistic activity. The AgNPs also exerted strong synergistic anticandidal activity when they were combined with amphotericin b. The AgNPs had high antioxidant activity and reducing power. Overall, the results confirmed the bio-potentials of the synthesized AgNPs using WRA, which could have applications in the biomedical, cosmetic, pharmaceutical, food preservation and packaging industries. PMID- 27261724 TI - Preparation and characterization of cationic and amphoteric mannans from Candida albicans. AB - Cationic and amphoteric mannans from Candida albicans were prepared by chemical modification with (3-chloro-2-hydroxypropyl)trimethylammonium chloride (CHPTAC) and sodium chloroacetate under aqueous alkaline conditions. The optimal reaction conditions for mannan cationization were found to be 6h, 60 degrees C, and NaOH/CHPTAC ratio of 1.0. Adjusting the molar ratio of cationization agent to anhydromannose unit, cationic and amphoteric mannans with degree of substitution ranging from 0.07 to 0.57 were obtained. Their structure was confirmed by elemental analysis as well as FTIR and NMR spectroscopies. Moderate decrease of molecular weight of both cationic and amphoteric mannans was recorded by size exclusion chromatography. With increasing level of modification, reduction of the antibody-binding capacity was observed by enzyme-linked immunosorbent assay. PMID- 27261725 TI - Morphological, physical, antimicrobial and release properties of ZnO nanoparticles-loaded bacterial cellulose films. AB - Bacterial cellulose (BC) monolayer and multilayer films, incorporating 5wt.% ZnO nanoparticles (NPs) have been obtained. Ultrasound (US) irradiation (40kHz) was applied during ZnO-BC nanocomposites preparation. X-ray diffraction (XRD) patterns showed that ZnO NPs were crystallized in their pure phase. SEM scanning electron microscopy (SEM) results indicated that US treatment causes to decrease ZnO particle size, forming a stable hybrid nanostructure and evenly distributed ZnO NPs coated BC nanofibers. ZnO NPs enhanced the mechanical properties and diminished water vapor permeability and moisture absorption of BC films. Antibacterial activity of ZnO-BC films against Staphylococcus aureus was more than Escherichia coli. The antibacterial activity was enhanced with the utilization of US irradiation. The ZnO release was influenced by films composition; the multilayer and US treated films being promising in order to achieve controlled release of ZnO. Results suggest that ZnO-BC films may be used as controlled release antimicrobial food active packaging. PMID- 27261726 TI - Coaggregation of mineral filler particles and starch granules as a basis for improving filler-fiber interaction in paper production. AB - The sustainable, efficient use of renewable bio-based additives in the production of various materials fits well into the concept of sustainability. Here, the concept of coaggregation of mineral filler particles and starch granules for improving filler-fiber interaction in paper-based cellulosic networks is presented. Coaggregation of precipitated calcium carbonate filler particles and uncooked, unmodified corn starch granules by cationic polyacrylamide (a cationic high molecular weight polymer flocculant) in combination with bentonite (an anionic microparticle) prior to addition to cellulosic fiber slurry delivered enhanced filler bondability with cellulosic fibers. For instance, under the conditions studied, preaggregation resulted in an increase in filler bondability factor from 9.24 to 15.21 at starch dosage of 1% (on the basis of the dry weight of papermaking stock). The swelling and gelatinization of the starch granules in starch-filler preaggregates or hybrids enabled the "bridging" of the gaps in cellulosic networks, leading to structural consolidation and strength enhancement. PMID- 27261727 TI - Biological evaluation of N-2-hydroxypropyl trimethyl ammonium chloride chitosan as a carrier for the delivery of live Newcastle disease vaccine. AB - Mucosal immune system plays a very important role in antiviral immune response. We prepared Newcastle disease viruses (NDV) encapsulated in N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) nanoparticles (NDV/La Sota-N-2 HACC-NPs) by an ionic cross linking method, and assessed the potential of N-2 HACC-NPs as a mucosal immune delivery carrier. The properties of the nanoparticles were determined by transmission electron microscopy, Zeta potential and particle size analysis, encapsulation efficiency and loading capacity. NDV/La Sota-N-2-HACC-NPs have regular spherical morphologies and high stability; with 303.88+/-49.8nm mean diameter, 45.77+/-0.75mV Zeta potential, 94.26+/-0.42% encapsulation efficiency and 54.06+/-0.21% loading capacity. In vitro release assay indicated that the release of NDV from NDV/La Sota-N-2-HACC-NPs is slow. The NDV/La Sota-N-2-HACC-NPs have good biological characteristics, very low toxicity and high level of safety. Additionally, specific pathogen-free chickens immunized with NDV/La Sota-N-2-HACC-NPs showed much stronger cellular, humoral and mucosal immune responses than commercial attenuated live Newcastle disease vaccine, and NDV/La Sota-N-2-HACC-NPs reached the sustainable release effect. Our study here provides a foundation for the further development of mucosal vaccines and drugs, and the N-2-HACC-NPs should be a potential drug delivery carrier with immense potential in medical applications. PMID- 27261728 TI - Active bio-based food-packaging: Diffusion and release of active substances through and from cellulose nanofiber coating toward food-packaging design. AB - Cellulose nanofibers (CNFs) were recently investigated for the elaboration of new functional food-packaging materials. Their nanoporous network was especially of interest for controlling the release of active species. Qualitative release studies were conducted, but quantification of the diffusion phenomenon observed when the active species are released from and through CNF coating has not yet been studied. Therefore, this work aims to model CNF-coated paper substrates as controlled release system for food-packaging using release data obtained for two model molecules, namely caffeine and chlorhexidine digluconate. The applied mathematical model - derived from Fickian diffusion - was validated for caffeine only. When the active species chemically interacts with the release device, another model is required as a non-predominantly diffusion-controlled release was observed. From caffeine modeling data, a theoretical active food-packaging material was designed. The use of CNFs as barrier coating was proved to be the ideal material configuration that best meets specifications. PMID- 27261729 TI - Silver coated anionic cellulose nanofiber composites for an efficient antimicrobial activity. AB - Herein, we report a comparative study of silver coated anionic cellulose nanocomposite before (CMC-Ag) and after (AgNPs/CMC) chemical reduction for antibacterial activity. Cellulose nanofibers were prepared by deacetylation of electrospun cellulose acetate nanofibers, which were then treated with sodium chloroacetate to prepare anionic cellulose nanofibers (CMC). Aqueous AgNO3 solution with different concentrations was employed to produce nanofiber composites. To obtain AgNPs/CMC, the resultant Ag/CMC nanofibers were chemically reduced with NaBH4. The nanocomposites were characterized by FE-SEM, FTIR, XPS and SEM-EDS. Antimicrobiality tests were conducted using S. aureus and Escherichia coli bacteria following standard test method JIS L1902, 2008. The EDS results confirmed higher silver content in CMC-Ag nanofibers than AgNPs/CMC nanofibers. The antimicrobial test and EDS results demonstrated higher silver release (larger halo width) by the former in comparison to later which confers better antimicrobiality by CMC-Ag nanofibers. PMID- 27261730 TI - Water-soluble cellulose acetate from waste cotton fabrics and the aqueous processing of all-cellulose composites. AB - The objective of this study is to explore the possibility of using waste cotton fabrics (WCFs) as low cost feedstock for the production of value-added products. Our previous study (Tian et al., 2014) demonstrated that acidic ionic liquids (ILs) can be highly efficient catalysts for controllable synthesis of cellulose acetate (CA) due to their dual function of swelling and catalyzing. In this study, an optimized "quasi-homogeneous" process which required a small amount of acidic ILs as catalyst was developed to synthesize water-soluble CA from WCFs. The process was optimized by varying the amounts of ILs and the reaction time. The highest conversion of water-soluble CA from WCFs reached 90.8%. The structure of the obtained water-soluble CA was characterized and compared with the original WCFs. Moreover, we demonstrate for the first time that fully bio-based and transparent all-cellulose composites can be fabricated by simple aqueous blending of the obtained water-soluble CA and two kinds of nanocelluloses (cellulose nanocrystals and cellulose nanofibrils), which is attractive for the applications in disposable packaging materials, sheet coating and binders, etc. PMID- 27261731 TI - New blends of ethylene-butyl acrylate copolymers with thermoplastic starch. Characterization and bacterial biodegradation. AB - Ethylene-butyl acrylate copolymer (EBA) with 13% of butyl acrylate content was used to produce blends with 10, 30 and 60% of thermoplastic starch (TPS) plasticized with glycerol. Ethylene-acrylic acid copolymer (EAA) was used as compatibilizer at 20% content with respect to EBA. The blends were characterized by X-ray diffraction, ATR-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM), water-Contact Angle measurements (CA), Differential Scanning Calorimetry (DSC) and Stress-strain mechanical tests. Initiated autoxidation of the polymer blends was studied by chemiluminescence (CL) confirming that the presence of the polyolefin-TPS interphase did not substantially affect the oxidative thermostability of the materials. Three bacterial species have been isolated from the blend films buried in soil and identified as Bacillus subtilis, Bacillus borstelensis and Bacillus licheniformis. Biodegradation of the blends (28days at 45 degrees C) was evaluated by carbon dioxide measurement using the indirect impedance technique. PMID- 27261732 TI - Antibiofilm activity of carboxymethyl chitosan on the biofilms of non-Candida albicans Candida species. AB - Although most cases of candidiasis have been attributed to Candida albicans, non C. albicans Candida species have been isolated in increasing numbers in patients. In this study, we determined the inhibition of carboxymethyl chitosan (CM chitosan) on single and mixed species biofilm of non-albicans Candida species, including Candida tropicalis, Candida parapsilosis, Candida krusei and Candida glabrata. Biofilm by all tested species in microtiter plates were inhibited nearly 70%. CM-chitosan inhibited mixed species biofilm in microtiter plates and also on medical materials surfaces. To investigate the mechanism, the effect of CM-chitosan on cell viability and biofilm growth was employed. CM-chitosan inhibited Candida planktonic growth as well as adhesion. Further biofilm formation was inhibited with CM-chitosan added at 90min, 12h or 24h after biofilm initiation. CM-chitosan was not only able to inhibit the metabolic activity of Candida cells, but was also active upon the establishment and the development of biofilms. PMID- 27261733 TI - Processing and characterization of polyols plasticized-starch reinforced with microcrystalline cellulose. AB - Biocomposites suitable for short-life applications such as food packaging were prepared by melt processing and investigated. Biocomposites studied are wheat starch plasticized with two different molecular weight polyols (glycerol and sorbitol) and reinforced with various amounts of microcrystalline cellulose. The effect of the plasticizer type and the filler amount on the processing properties, the crystallization behavior and morphology developed for the materials, and the influence on thermal stability, dynamic mechanical properties and water absorption behavior were investigated. Addition of microcrystalline cellulose led to composites with good filler-matrix adhesion where the stiffness and resistance to humidity absorption were improved. The use of sorbitol as a plasticizer of starch also improved the stiffness and water uptake behavior of the material as well as its thermal stability. Biodegradable starch-based materials with a wide variety of properties can be tailored by varying the polyol plasticizer type and/or by adding microcrystalline cellulose filler. PMID- 27261734 TI - Maleimide-grafted cellulose nanocrystals as cross-linkers for bionanocomposite hydrogels. AB - This article deals with the preparation of bionanocomposite hydrogels from natural polymers and nanoentities, an emerging class of materials for biotechnological and biomedical applications. Herein, the applicability of the Diels-Alder "click" reaction to the design of bionanocomposite hydrogels from furan modified gelatin using maleimide-functionalized cellulose nanocrystals as multifunctional cocross-linkers is demonstrated. The functionalization of cellulose nanocrystals with maleimide moieties was confirmed by XPS. The swelling and rheological properties of the resulting bionanocomposite confirmed the formation of hydrogel networks with covalently embedded nanoentities. The Diels Alder reaction resulted in the formation of stiffer networks with lower swelling ratios due to the formation of additional cross-linking points. The designed "click" strategy proved to be a promising candidate for the formation of fully renewable bionanocomposite hydrogels. PMID- 27261735 TI - 3,6-O-[N-(2-Aminoethyl)-acetamide-yl]-chitosan exerts antibacterial activity by a membrane damage mechanism. AB - A novel chitosan derivative, 3,6-O-[N-(2-aminoethyl)-acetamide-yl]-chitosan (AACS), was successfully prepared to improve water solubility and antibacterial activity of chitosan. AACS had good antibacterial activity, with minimum inhibitory concentrations of 0.25mg/mL, against Escherichia coli and Staphylococcus aureus. Cell membrane integrity, electric conductivity and NPN uptake tests showed that AACS caused quickly increasing the release of intracellular nucleic acids, the uptake of NPN, and the electric conductivity by damaging membrane integrity. On the other hand, hydrophobicity, cell viability and SDS-PAGE experiments indicated that AACS was able to reduce the surface hydrophobicity, the cell viability and the intracellular proteins through increasing membrane permeability. SEM observation further confirmed that AACS could kill bacteria via disrupting their membranes. All results above verified that AACS mainly exerted antibacterial activity by a membrane damage mechanism, and it was expected to be a new food preservative. PMID- 27261737 TI - Purification, characterization and anti-proliferation activities of polysaccharides extracted from Viscum coloratum (Kom.) Nakai. AB - Three polysaccharides, VCP1, VCP2 and VCP3 were isolated from Viscum coloratum (Kom.) Nakai using DEAE-cellulose chromatography. VCP1 (32KDa) was composed of glucose, galactose, arabinose, rhamnose and mannose, while VCP2 (280KDa) and VCP3 (21KDa) were consisted of glucose, galactose, arabinose, rhamnose, mannose, glucuronic acid and galacturonic acid. The optical rotation was measured at 20+1 degrees C. The characteristic absorptive bands of purified fraction were determined by FT-IR. (13)C NMR spectroscopy analysis showed that VCP1 was a neutral polysaccharide, and VCP2 and VCP3 were RG-I type pectin. The linkage patterns of VCP2 were evaluated by methylation analysis: 1,5-linked Araf, 1,4 linked Galp, 1,2-linked Rhap, and 1,2,4-linked Rhap. The degree of esterification was 50%. The anti-proliferation ability against HepG2 cells and HepG2.2.15 cells of VCP2 was stronger than VCP1 and VCP3. So the polysaccharides from Viscum coloratum (Kom.) Nakai could be used as potential natural sources with inhibiting tumor cells proliferation. PMID- 27261736 TI - Exopolysaccharide from Trichoderma pseudokoningii induces macrophage activation. AB - In this study, we evaluated the immunomodulatory activity of an exopolysaccharide (EPS) derived from Trichoderma pseudokoningii and investigated the molecular mechanism of EPS-mediated activation of macrophages. Results revealed that EPS could significantly induce the production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and enhance phagocytic activity in RAW 264.7 cells. Immunofluorescence staining indicated that EPS promoted the nuclear translocation of nuclear factor (NF)-kappaB p65 subunit. Western blot analysis showed that EPS increased the expression of inducible nitric oxide synthase (iNOS) protein, the degradation of IkappaB-alpha and the phosphorylation of mitogen-activated protein kinases (MAPKs). Furthermore, pretreatment of RAW 264.7 cells with specific inhibitors of NF-kappaB and MAPKs significantly attenuated EPS-induced TNF-alpha and IL-1beta production. EPS also induced the inhibition of cytokine secretion by special antibodies against Toll-like receptor 4 (TLR4) and Dectin-1. These data suggest that EPS from Trichoderma pseudokoningii activates RAW 264.7 cells through NF-kappaB and MAPKs signaling pathways via TLR4 and Dectin-1. PMID- 27261739 TI - New studies on basil (Ocimum bacilicum L.) seed gum: Part II-Emulsifying and foaming characterization. AB - BSG is composed of two major fractions with different molecular weight: PER-BSG (5980kgmol(-1)) and SUPER-BSG (1045kgmol(-1)). In the present work, the emulsifying and foaming properties of BSG and its fractions were investigated as a function of molecular weight, chain flexibility and physicochemical features (protein and acid uronic content). BSG prevented creaming of emulsion for 4 weeks. This high stabilization may be related to formation a solid-like structure and viscoelastic film of BSG around oil droplets which protected oil droplets against aggregation. The low molecular weight fraction (SUPER-BSG) created more stable emulsion than high molecular weight fraction (PER-BSG). The foam capacity and stability of albumin solution increased by adding BSG. The highest foam stability was observed at the highest gum concentration (0.3% w/v). Removing protein moieties of BSG led to emulsion and foam stabilization properties of BSG weakened, which presents the importance of protein in emulsifying and foaming properties of BSG. PMID- 27261738 TI - Methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan as a new chitosan derivative: Synthesis, characterization, cytotoxicity and antibacterial activity. AB - Chitosan, as a biocompatible polymer, is very attractive for biomedical applications. Continues studies are performing for improving its physicochemical features in order to make it more suitable for such approaches. In this study, methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan (MABCC) was synthesized,as a new chitosan derivative, in three steps. The investigations were carried out using FTIR, NMR, TGA and zeta potential measurement. Antibacterial and cell viability assessments were performed on four bacterial strains and two cell lines respectively. FTIR and NMR results showed that all substitution reactions were successfully carried out. Zeta potential of MABCC at various pH especially alkaline pH was greater than chitosan and it revealed increasing the solubility of the derivative. Antibacterial activity of MABCC was extremely greater than chitosan especially in Gram positive bacteria.Furthermore,it had no significant cytotoxicity against MCF-7 and Skov-3 cell lines in comparison to chitosan. These findings confirm that this new derivative can be introduced as a suitable compound for biomedical purposes. PMID- 27261740 TI - Modification mechanism of sesbania gum, and preparation, property, adsorption of dialdehyde cross-linked sesbania gum. AB - This paper studied the modification mechanism of Sesbania gum (SG) by means of the variations in the numbers of surface hydroxyl groups on the granules, Schiff's agent coloration of aldehyde groups, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), energy dispersive spectrum (EDS), etc., and also examined the preparation, property and adsorption of dialdehyde cross-linked sesbania gum (DCLSG). The results showed that the surface hydroxyl numbers of cross-linked sesbania gum (CLSG) decreased with increasing the cross-linking degree. The distribution of the aldehyde groups on the DCLSG particles was nonuniform because most of aldehyde groups mainly located on the edge of particles. The cross-linking occurred only on the surface of SG particles. The oxidization occurred not only on the surface of SG particles, but also in the interior of particles. The cross-linking or oxidization changed the thermal properties, and reduced the swelling power, viscosity, alkali and acid resistance of SG. PMID- 27261741 TI - A thermo-responsive and photo-polymerizable chondroitin sulfate-based hydrogel for 3D printing applications. AB - The aim of this study was to design a hydrogel system based on methacrylated chondroitin sulfate (CSMA) and a thermo-sensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate)-polyethylene glycol triblock copolymer (M15P10) as a suitable material for additive manufacturing of scaffolds. CSMA was synthesized by reaction of chondroitin sulfate with glycidyl methacrylate (GMA) in dimethylsulfoxide at 50 degrees C and its degree of methacrylation was tunable up to 48.5%, by changing reaction time and GMA feed. Unlike polymer solutions composed of CSMA alone (20% w/w), mixtures based on 2% w/w of CSMA and 18% of M15P10 showed strain-softening, thermo-sensitive and shear-thinning properties more pronounced than those found for polymer solutions based on M15P10 alone. Additionally, they displayed a yield stress of 19.2+/-7.0Pa. The 3D printing of this hydrogel resulted in the generation of constructs with tailorable porosity and good handling properties. Finally, embedded chondrogenic cells remained viable and proliferating over a culture period of 6days. The hydrogel described herein represents a promising biomaterial for cartilage 3D printing applications. PMID- 27261742 TI - Novel cross linked guar gum-g-poly(acrylate) porous superabsorbent hydrogels: Characterization and swelling behaviour in different environments. AB - A new series of eco-friendly cross linked guar gum-g-poly(acrylate) porous superabsorbent hydrogels was prepared by in situ grafting polymerization and cross-linking on to a natural guar gum employing N,N-methylene bis acrylamide as cross linker. Morphological and structural characterization of the prepared hydrogels (SPHs) done by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and solid state C(13) NMR spectroscopy confirmed formation of porous grafted and crosslinked hydrogel structure. Increase in cross linker concentration in the feed mass exhibited decrease in porosity and increase in density of the hydrogels. Swelling of an optimized hydrogel (SPH) in response to external stimuli namely, salt solutions, fertilizer solutions, temperature, and pH exhibited high swelling ratios in various environments. Swelling rate of the SPH was faster than the corresponding nonporous superabsorbent hydrogel. The prepared hydrogels can serve as excellent carriers of pesticides, fertilizers and agriculturally important microbes. Biocontrol formulations based on a representative SPH exhibited excellent shelf-life characteristics and bioefficacy against phytopathogenic fungus Pythium aphanidermatum. PMID- 27261743 TI - Toll-like receptor 4-related immunostimulatory polysaccharides: Primary structure, activity relationships, and possible interaction models. AB - Toll-like receptor (TLR) 4 is an important polysaccharide receptor; however, the relationships between the structures and biological activities of TLR4 and polysaccharides remain unknown. Many recent findings have revealed the primary structure of TLR4/MD-2-related polysaccharides, and several three-dimensional structure models of polysaccharide-binding proteins have been reported; and these models provide insights into the mechanisms through which polysaccharides interact with TLR4. In this review, we first discuss the origins of polysaccharides related to TLR4, including polysaccharides from higher plants, fungi, bacteria, algae, and animals. We then briefly describe the glucosidic bond types of TLR4-related heteroglycans and homoglycans and describe the typical molecular weights of TLR4-related polysaccharides. The primary structures and activity relationships of polysaccharides with TLR4/MD-2 are also discussed. Finally, based on the existing interaction models of LPS with TLR4/MD-2 and linear polysaccharides with proteins, we provide insights into the possible interaction models of polysaccharide ligands with TLR4/MD-2. To our knowledge, this review is the first to summarize the primary structures and activity relationships of TLR4-related polysaccharides and the possible mechanisms of interaction for TLR4 and TLR4-related polysaccharides. PMID- 27261744 TI - Self-sterilized composite membranes of cellulose acetate/polyethylene glycol for water desalination. AB - Cellulose acetate/Polyethylene glycol-600 composite membranes were fabricated by two step phase inversion procedure and modified by in-situ reduction of silver nitrate. FTIR spectra demonstrated the existence of functional groups for bonding of silver with oxygen at 370cm(-1), 535cm(-1). The XRD diffractogram indicates characteristic peaks at 2theta values of 38.10 degrees , 44.30 degrees , 64.40 degrees , and 77.30 degrees which confirm the successful incorporation of silver within matrix of composite membranes. The morphology of composite membranes with appearances of spongy voids was exemplified from the scanning electron microscope. The atomic force microscopy was used to determine the increase in the surface roughness of the membranes. The increase in hydrophilicity, measured through contact angle, is rendered to the embedment of silver. The modification of membranes increased the flux from 0.80 to 0.95L/hr.m(2). The resulting membranes have outstanding ability to fight against gram negative Escherichia Coli and Bacillus Sabtilus. The novel cellulose acetate/polyethylene glycol membranes customized with silver have paved the path for evolution of axenic membranes. PMID- 27261745 TI - Mechanically flexible and optically transparent three-dimensional nanofibrous amorphous aerocellulose. AB - Aerocelluloses are considered as "third generation" aerogels after the silica and synthetic polymer-based ones. However, their brittleness and low optical translucency keep quite narrow their fields of applications. Here, both issues are addressed successfully through the fabrication of flexible and mechanically robust amorphous aerocellulose with high optical transparency, using trifluoroacetic acid as a solvent and ethanol as a non-solvent. The developed aerocellulose displays a meso-macroporous interconnected nanofibrous cellulose skeleton with low density and high specific surface area. We demonstrate its high efficiency as supporting matrix for nanoscale systems by incorporating a variety of colloidal quatum dots, that provide bright and stable photoluminescence to the flexible aerocellulose host. PMID- 27261746 TI - Preparation and evaluation of naringenin-loaded sulfobutylether-beta cyclodextrin/chitosan nanoparticles for ocular drug delivery. AB - The aim of this study was to prepare and characterize the naringenin-loaded sulfobutylether-beta-cyclodextrin/chitosan nanoparticles (Nag-CD/CS-NPs) and evaluate their potential for the topical ophthalmic delivery. Naringenin was first complexed with sulfobutylether-beta-cyclodextrin (SBE-beta-CD), which can significantly enhance the solubility of poorly soluble drugs. Then, nanoparticles were prepared by ionic gelation of chitosan with SBE-beta-CD, and their in vitro and vivo properties were investigated, respectively. The resulting nanoparticles showed an average size of 446.4+/-112.8nm and zeta potential of +22.5+/-4.91mV with predominant spherical in shape. The FT-IR and DSC confirmed the formation of Nag-CD/CS-NPs. The in vitro release study indicated that Nag-CD/CS-NPs achieved moderate sustained-release effect, and the in vivo study revealed that the prepared nanoparticles was nonirritating to rabbit's eye and had better ability to prolong the residence time than the naringenin suspension, which can significantly increase naringenin bioavailability in the aqueous humor. In conclusion, the developed CD/CS nanoparticles offer a potential alternative for the ocular administration of poorly soluble drugs. PMID- 27261747 TI - Polysaccharide structures and interactions in a lithium chloride/urea/water solvent. AB - The molten salt hydrate, lithium chloride (LiCl)/urea/water has previously been shown to swell cellulose, but there has so far been no work done to explore its effect on other polysaccharides. In this paper we have investigated the solvent effects of LiCl/urea/water on four natural polysaccharides. Fenugreek gum and xyloglucan, which are both highly branched, were found to increase in viscosity in LiCl/urea/water relative to water, possibly due to the breakage of all intra molecular associations whereas the viscosity of konjac glucomannan which is predominantly unbranched did not change. Locust bean gum (LBG) had a lower viscosity in LiCl/urea/water compared to water due to the disruption of aggregates. Confocal microscopy showed that fenugreek gum and LBG are able to bind to cellulose in water, however, the conformational change of fenugreek gum in these solvent conditions inhibited it from binding to cellulose in LiCl/urea/water whereas conformational change allowed xyloglucan to bind to cellulose in LiCl/urea/water whilst it was unable to bind in water. Konjac glucomannan did not bind to cellulose in either solvent system. These results provide new insights into the impact of polysaccharide fine structure on conformational change in different solvent environments. PMID- 27261748 TI - Fabrication of magnetic hydroxypropyl cellulose-g-poly(acrylic acid) porous spheres via Pickering high internal phase emulsion for removal of Cu(2+) and Cd(2.). AB - A series of magnetic hydroxypropyl cellulose-g-poly(acrylic acid) porous spheres were prepared via O/W Pickering high internal phase emulsions (HIPEs) integrated precipitation polymerization. The structure and composition of modified Fe3O4 and porous structures were characterized by TEM, XRD, TGA and SEM. The results indicated that the silanized Fe3O4 can influence greatly the pore structure of magnetic porous sphere in addition to non-negligible impacts of the proportion of mixed solvent and co-surfactant. The adsorption experiment demonstrated that the adsorption equilibrium can be reached within 40min and the maximal adsorption capacity was 300.00mg/g for Cd(2+) and 242.72mg/g for Cu(2+), suggesting its fast adsorption kinetics and high adsorption capacity. After five adsorption desorption cycles, no significant changes in the adsorption capacity were observed, suggesting its excellent reusability. The magnetic porous sphere can be easily separated from the solution and then find its potential as a recyclable material for highly efficient removal of heavy metals. PMID- 27261749 TI - Enhanced surface functionality and microbial fuel cell performance of chitosan membranes through phosphorylation. AB - The effects of plasticization and cross-linking on the performance of chitosan as promising proton exchange membranes (PEMs) for bioelectricity generation in microbial fuel cells (MFCs) were investigated. The physico-chemical properties of chitosan (CS), sorbitol-chitosan (S-CS), phosphorylated-chitosan (CS-P) and phosphorylated-sorbitol-chitosan (S-CS-P) membranes were investigated by FESEM EDS, FTIR-ATR, XRD, TGA, tensile strength and sorption studies. The performance of the fabricated PEMs was assessed by power density and cation exchange capacity (CEC). Maximum power densities achieved were 130.03, 20.76, 94.59 and 7.42mW/m(2) for CS-P, S-CS-P, S-CS and CS membranes respectively. Phosphorylation of the CS membranes increased CEC and tensile strength, attributed to an increase in bonded amide and phosphate ionic surface groups. Further, 49.07% COD removal from municipal wastewater was achieved with CS-P membranes. Thus, through chemical modifications, the physico-chemical and mechanical properties of natural abundant biopolymer chitosan can be enhanced for its use as an environmentally sustainable PEM in MFC technology. PMID- 27261750 TI - Injectable long acting chitosan/tripolyphosphate microspheres for the intra articular delivery of lornoxicam: Optimization and in vivo evaluation. AB - Chitosan microspheres were formulated for the intra-articular delivery of lornoxicam in knee osteoarthritis, to minimize associated side-effects after prolonged oral administration. Ionotropic-gelation technique was employed using tripolyphosphate as anionic cross-linker. Full-factorial design experiment was conducted to optimize lornoxicam entrapment-efficiency%. Formulations were assessed for their particle size, in-vitro drug release, Scanning electron microscopy, Differential-scanning-calorimetry and Fourier transform infra-red spectroscopy studies. Changing independent variables, chitosan pH, TPP pH and lornoxicam concentration resulted in different values of entrapment-efficiency% ranging from 13.5%+/-0.35 to 59.5%+/-2.2. Particle size ranged from 3.57MUm+/ 0.02 to 6.12MUm+/-0.00 and lornoxicam%release was prolonged for up to 8days. SEM results showed spherical shape of the microspheres. FTIR and DSC studies confirmed the crosslinking of chitosan with tripolyphosphate. In-vivo therapeutic effect of lornoxicam microspheres was investigated using Monosodiumiodoacetate (MIA) induced osteoarthritis model in rats. Optimized formula showed long-term in vivo anti-inflammatory effect relative to lornoxicam solution injected intra articularly with significant reduction of histological, inflammatory and biochemical parameters of osteoarthritis. PMID- 27261751 TI - A facile route to prepare cellulose-based films. AB - Cellulose is the most abundant renewable and biodegradable material available in nature. Its insoluble character in water as well as common organic and inorganic liquids, however, curtails the wholesome utility. The continuous rise for biodegradable products based on cellulose coupled with its intrinsic ability to form a viable substitute for the petroleum-based materials necessitates the critical need for solubilizing the cellulose. Herein, we demonstrate the feasibility of ZnCl2 solutions, especially the 64-72% concentrations, to dissolve cellulose. FTIR results suggest that Zn(2+) ions promote Zn?O3H interactions, which in-turn weaken the intrinsic O3H?O5 hydrogen bonds that are responsible for strengthening the cellulose chains. Interestingly, Ca(2+) ions promote interactions among the Zn-cellulose chains leading to the formation of nano fibrils and yield gelling solutions. The tensile strength of the Ca(2+) added Zn cellulose films increases by around 250% compared to the Zn-cellulose films. Overall, utilization of inorganic salt solutions to solubilize and crosslink cellulose is cost-effective, recyclable and certainly stands out tall among the other available systems. More importantly, the proposed protocol is simple and is a "green" process, and thus its large-scale adaptability is quite feasible. We strongly believe that the outcome opens up a new window of opportunities for cellulose in the biomedical, pharmaceutical, food and non-food applications. PMID- 27261752 TI - Dosage effects of Waxy gene on the structures and properties of corn starch. AB - The objective of this study was to understand dosage effects of the Waxy gene on the structures of amylose and amylopectin and on the properties of corn starch. Reciprocal crossing of isogenic normal and waxy corn lines was conducted to develop hybrids with different dosages (0, 1, 2, 3) of Waxy gene in the endosperm. The amylose content of starch and proportions of branch chains of DP 17-30 and extra-long branch chains (DP>100) of amylopectin were positively correlated with the Waxy-gene dosage. Proportions of short (DP<17) and long branch-chains (DP 30-80), however, were negatively correlated with the Waxy-gene dosage. The gelatinization conclusion-temperature and temperature-range of the starch were negatively correlated with the Waxy-gene dosage, indicating that amylose facilitated dissociation of the surrounding crystalline regions. These results helped us understand the function of granule-bound starch synthase I in the biosynthesis of amylose and amylopectin and impacts of Waxy-gene dosages on the properties of corn starch. PMID- 27261753 TI - Sulfated levan from Halomonas smyrnensis as a bioactive, heparin-mimetic glycan for cardiac tissue engineering applications. AB - Chemical derivatives of levan from Halomonas smyrnensis AAD6(T) with low, medium and high levels of sulfation were synthesized and characterized by FTIR and 2D NMR. Sulfated levan samples were found to exhibit anticoagulation activity via the intrinsic pathway like heparin in a dose-dependent manner. Exceptionally high heparin equivalent activity of levan sulfate was shown to proceed via thrombin inhibition where decreased Factor Xa activity with increasing concentration was observed in antithrombin tests and above a certain concentration, levan sulfate showed a better inhibitor activity than heparin. In vitro experimental results were then verified in silico by docking studies using equilibrium structures obtained by molecular dynamic simulations and results suggested a sulfation dependent binding mechanism. With its high biocompatibility and heparin mimetic activity, levan sulfate can be considered as a suitable functional biomaterial to design biologically active, functionalized, thin films and engineered smart scaffolds for cardiac tissue engineering applications. PMID- 27261754 TI - The physico-chemical properties of chia seed polysaccharide and its microgel dispersion rheology. AB - The polysaccharide gel layer surrounding hydrated chia seeds was extracted using water and isolated by ethanol precipitation. The freeze-dried sample consisted of ~95% non-starch polysaccharides (35% w/w neutral soluble fraction and 65% w/w negatively charged insoluble fraction). The soluble polysaccharide fraction has molar mass, root-mean square radius and intrinsic viscosity of ~5*10(5)g/mol, 39nm and 719mL/g, respectively. The whole polysaccharide (included soluble and insoluble fractions) when dispersed in water showed presence of irregular shape, fibrous microgel particles with an average size (D4,3) of ~700MUm. Rheological measurements indicated a 'weak' viscoelastic gel and strong shear dependent properties even at low concentration (0.05% w/w). The viscosity of the dispersion was fairly resistant to variations in temperatures (20-80 degrees C), pH (4-12), ionic strengths (0.01-0.5M NaCl) and cation types (MgCl2, CaCl2, NaCl and KCl). The swollen microgel particles dispersed in soluble polysaccharide continuous phase provided complex and potentially useful rheological properties in food systems. PMID- 27261755 TI - Preparation and characterization of superhydrophobic organic-inorganic hybrid cotton fabrics via gamma-radiation-induced graft polymerization. AB - A new kind of non-fluorine-based organic-inorganic hybrid superhydrophobic cotton fabric was successfully prepared by simultaneous radiation-induced graft polymerization of gamma-methacryloxypropyl trimethoxy silane (MAPS) and subsequent end-capping modification with hexamethyldisilazane (HMDS). The chemical structure and surface topography of the pristine and modified cotton fabrics were investigated in detail by ATR-FTIR, XPS, (29)Si NMR, SEM and TGA to confirm that the graft reaction and end-capping modification had taken place. The above results demonstrated that the grafting polymerization and following end capping reaction were completed, and a grafting layer was immobilized onto the surface of the cotton fabric. Surface wettability measurement and oil-water separation showed that the modified cotton surface not only exhibited the superhydrophobicity with a water contact angle of 165 degrees , but also afforded a high efficiency of oil-water separation (96%). In particular, this modified cotton fabric retains superhydrophobicity even after 30 laundering cycles or 400 cycles of abrasion. PMID- 27261756 TI - Adsorption and photocatalytic degradation of anionic dyes on Chitosan/PVA/Na Titanate/TiO2 composites synthesized by solution casting method. AB - Chitosan/PVA/Na-titanate/TiO2 composite was synthesized by solution casting method. The composite was analyzed via Fourier Transform Infrared Spectroscopy, X ray diffraction, Field Emission Scanning Electron Microscopy, Thermal gravimetric analysis and water stability test. Incorporation of Na-titanate shown decrease of crystallinity for chitosan but increase water stability. However, the composite structure was deteriorated with considerable weight loss in acidic medium. Two anionic dyes, methyl orange and congo red were used for the adsorption test. The adsorption behavior of the composites were described by pseudo-second-order kinetic model and Lagergren-first-order model for methyl orange and congo red, respectively. For methyl orange, adsorption was started with a promising decolorization rate. 99.9% of methyl orange dye was removed by the composite having higher weightage of chitosan and crystalline TiO2 phase. On the other hand, for the congo red the composite having higher chitosan and Na-titanate showed an efficient removal capacity of 95.76%. UV-vis results showed that the molecular backbone of methyl orange and congo red was almost destroyed when equilibrium was obtained, and the decolorization rate was reaching 100%. Kinetic study results showed that the photocatalytic degradation of methyl orange and congo red could be explained by Langmuir-Hinshelwood model. Thus, chitosan/PVA/Na titanate/TiO2 possesses efficient adsorptivity and photocatalytic property for dye degradation. PMID- 27261757 TI - Functionalization of MWCNT and their application in properties development of green wood nanocomposite. AB - Starch based wood nanocomposites (WSNC) were prepared successfully from starch and soft wood with multi-walled carbon nanotube (MWCNT) as nano reinforcing agent through a completely green path. The most important part of this scheme was the use of water as the solvent. In this technique, starch was grafted with methylmethacrylate (MMA) and MWCNT was functionalised with hydroxyl groups (f MWCNT). Dimethyloldihydroxyethyleneurea (DMDHEU) was used as a cross-linker to prepare the green material from methylmethacrylate grafted starch (MMA-g-starch), soft wood flour and functionalised MWCNT. The functionalization of MWCNT was confirmed by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and Raman analysis. Different properties of the WSNC were investigated by varying the concentration of f-MWCNT. The prepared nanocomposites exhibited outstanding thermal stability, mechanical properties and water resistance capacity compared to untreated wood composites. The flammability of the wood composites decreased up to 30% with just addition of 0.50phr f-MWCNT. PMID- 27261758 TI - pH and temperature stability of (-)-epigallocatechin-3-gallate-beta-cyclodextrin inclusion complex-loaded chitosan nanoparticles. AB - The oxidative stability of (-)-epigallocatechin-3-gallate (EGCG) incorporated as inclusion complexes (ICs) in sulfobutylether-beta-cyclodextrin sodium (SBE-beta CD) and then ionotropically crosslinked with chitosan hydrochloride (CSH) into nanoparticles were investigated. EGCG-loaded CSH-SBE-beta-CD nanoparticles (CSNs) were physically unstable at higher pH and temperature. The particle size of CSNs was unchanged in the pH range of 3-5, but the microenvironment of EGCG-IC appeared to be intact until the pH increased to 6.5 by fluorescence spectroscopy. The physical structure of EGCG-ICs was also affected during storage in addition to CSNs, which was further affected as temperature increased from 25 to 55 degrees C. The decrease in antioxidant activities of EGCG-ICs and free EGCG with increasing pH, storage time and temperature were modest compared to the prominent decreases in antioxidant activities of EGCG-loaded CSNs. The extreme entrapment of EGCG-ICs and/or free EGCG in the aggregated CSNs restricted the release of EGCG, thus inhibiting the antioxidant activities. PMID- 27261759 TI - Cellobiose as a model system to reveal cellulose dissolution mechanism in acetate based ionic liquids: Density functional theory study substantiated by NMR spectra. AB - Cellulose dissolution mechanism in acetate-based ionic liquids was systematically studied in Nuclear Magnetic Resonance (NMR) spectra and Density Functional Theory (DFT) methods by using cellobiose and 1-butyl-3-methylimidazolium acetate (BmimAc) as a model system. The solubility of cellulose in ionic liquid increased with temperature increase in the range of 90-140 degrees C. NMR spectra suggested OAc(-) preferred to form stronger hydrogen bonds with hydrogen of hydroxyl in cellulose. Electrostatic potential method was employed to predict the most possible reaction sites and locate the most stable configuration. Atoms in molecules (AIM) theory was used to study the features of bonds at bond critical points and the variations of bond types. Simultaneously, noncovalent interactions were characterized and visualized by employing reduced density gradient analysis combined with Visual Molecular Dynamics (VMD) program. Natural bond orbital (NBO) theory was applied to study the noncovalent nature and characterize the orbital interactions between cellobiose and Bmim[OAc]. PMID- 27261760 TI - Revalorization of sunflower stalks as novel sources of cellulose nanofibrils and nanocrystals and their effect on wheat gluten bionanocomposite properties. AB - Novel gluten based bionanocomposites reinforced with cellulose nanofibrils (CNF) and cellulose nanocrystals (CNC) extracted from sunflower stalks by respectively a steam explosion treatment and a hydrolysis procedure, were prepared by casting/evaporation. The extracted cellulose nanomaterials, both CNC and CNF, were embedded in gluten matrix and their effect was investigated. Morphological investigations highlighted that gluten based bionanocomposites showed a homogenous morphology, the absence of visible cellulose nanoreinforcements, and the presence of holes for Gluten_CNF nanocomposites. Gluten_CNF showed a reduction of water vapour permeability coefficients but the values are higher respect to gluten reinforced with CNC. This behaviour could be related to the ability of CNC to increase the tortuous path of gas molecules. Moreover, the results from thermal, mechanical and barrier properties confirmed the strong interactions obtained between CNC and gluten matrix during the process. The study suggested the possibility to re-valorise agricultural wastes with potential applications as reinforcement in polymer matrix bionanocomposites. PMID- 27261761 TI - Ionic liquid pretreatment of biomass for sugars production: Driving factors with a plausible mechanism for higher enzymatic digestibility. AB - In this study, five ionic liquids (ILs) have been explored for biomass pretreatment for the production of fermentable sugar. We also investigated the driving factors responsible for improved enzymatic digestibility of various ILs treated biomass along with postulating the plausible mechanism thereof. Post pretreatment, mainly two factors impacted the enzymatic digestibility (i) structural deformation (cellulose I to II) along with xylan/lignin removal and (ii) properties of ILs; wherein, K-T parameters, viscosity and surface tension had a direct influence on pretreatment. A systematic investigation of these parameters and their impact on enzymatic digestibility is drawn. [C2mim][OAc] with beta-value 1.32 resulted 97.7% of glucose yield using 10 FPU/g of biomass. A closer insight into the cellulose structural transformation has prompted a plausible mechanism explaining the better digestibility. The impact of these parameters on the digestibility can pave the way to customize the process to make biomass vulnerable to enzymatic attack. PMID- 27261762 TI - Thermal and magnetic properties of chitosan-iron oxide nanoparticles. AB - Chitosan is a biopolymer widely used for biomedical applications such as drug delivery systems, wound healing, and tissue engineering. Chitosan can be used as coating for other types of materials such as iron oxide nanoparticles, improving its biocompatibility while extending its range of applications. In this work iron oxide nanoparticles (Fe3O4 NPs) produced by chemical precipitation and thermal decomposition and coated with chitosan with different molecular weights were studied. Basic characterization on bare and chitosan-Fe3O4 NPs was performed demonstrating that chitosan does not affect the crystallinity, chemical composition, and superparamagnetic properties of the Fe3O4 NPs, and also the incorporation of Fe3O4 NPs into chitosan nanoparticles increases the later hydrodynamic diameter without compromising its physical and chemical properties. The nano-composite was tested for magnetic hyperthermia by applying an alternating current magnetic field to the samples demonstrating that the heating ability of the Fe3O4 NPs was not significantly affected by chitosan. PMID- 27261763 TI - Identification and determination of the inulin content in the roots of the Northeast Brazilian species Pombalia calceolaria L. AB - A polysaccharide was extracted from the roots of Pombalia calceolaria, a plant used in folk medicine in Northeastern Brazil, by decoction followed by precipitation with methanol, yielding a concentration of 13.0% w/w, and purification with acetone. The molar mass peak was estimated to be 4.0*10(3)Da using gel permeation chromatography (GPC). Polarized light photomicrography of histological sections revealed the presence of inulin in the cortical parenchyma. The chemical composition of inulin was identified by 1D and 2D NMR and FT-IR spectroscopy and the findings were compared with the literature. This is the first time inulin has been identified on FT-IR and NMR for the species Pombalia calceolaria. PMID- 27261764 TI - Structural characterization and antidiabetic activity of a glucopyranose-rich heteropolysaccharide from Catathelasma ventricosum. AB - Polysaccharides, which are the main bioactive constituents of edible mushrooms, have been shown to have a variety of useful biological activities. In this study, a polysaccharide fraction from the edible mushroom Catathelasma ventricosum was purified using anion exchange and size exclusion chromatographies. The structure of the resulting polysaccharide, named CVP-1S, was characterized on the basis of partial acid hydrolysis, periodic acid oxidation, methylation analysis, gas chromatography-mass spectrometry, Fourier-transform infrared spectroscopy, 1D/2D NMR spectroscopy, scanning electron microscopy, and atomic force spectroscopy. The results showed that CVP-1S is a heteropolysaccharide consisting of glucose (94.2%), galactose (3.51%) and fucose (1.3%) with a molecular weight of 1.5*10(4)Da. Its backbone is mainly linked by (1->6)-beta-d-Glcp glycosidic bonds, and branches are attached to the backbone through 1,3-linked glycosidic bonds. CVP-1S was also found to have antioxidant, hypoglycemic, and hypolipidemic activities in the streptozoicin-induced diabetic mouse model. From these results, we conclude that CVP-1S should receive further attention as a potential agent for the treatment and prevention of diabetes. PMID- 27261765 TI - Modification biological activity of S and R forms of Proteus mirabilis and Burkholderia cepacia lipopolysaccharides by carrageenans. AB - The modification of biological features of S and R forms of Proteus mirabilis and Burkholderia cepacia LPS by kappa/iota and kappa/beta carrageenans was shown in Limulus activation test, ELISA, human complement activation and apoptotic assay. The role of positively charged substituent Ara4N in lipid A was evaluated as a suspected major domain for interactions with sulphate groups of carrageenans.The experiments obtained by three serological methods indicated that not only lipid A part of LPS but also polysaccharide elements such as core and O-specific chain are involved in interaction with carrageenes. Carrageenans turned out to be non cytotoxic for A549 cells and were able to inhibit the apoptotic effect caused by lipid A of P. mirabilis and B. cepacia. PMID- 27261766 TI - AR-V7 Protein in Circulating Tumor Cells-The Decider for Therapy? PMID- 27261767 TI - Use of Schizosaccharomyces strains for wine fermentation-Effect on the wine composition and food safety. AB - Schizosaccharomyces was initially considered as a spoilage yeast because of the production of undesirable metabolites such as acetic acid, hydrogen sulfide, or acetaldehyde, but it currently seems to be of great value in enology.o ced Nevertheless, Schizosaccharomyces can reduce all of the malic acid in must, leading to malolactic fermentation. Malolactic fermentation is a highly complicated process in enology and leads to a higher concentration of biogenic amines, so the use of Schizosaccharomyces pombe can be an excellent tool for assuring wine safety. Schizosaccharomyces also has much more potential than only reducing the malic acid content, such as increasing the level of pyruvic acid and thus the vinylphenolic pyranoanthocyanin content. Until now, few commercial strains have been available and little research on the selection of appropriate yeast strains with such potential has been conducted. In this study, selected and wild Sc. pombe strains were used along with a Saccharomyces cerevisiae strain to ferment red grape must. The results showed significant differences in several parameters including non-volatile and volatile compounds, anthocyanins, biogenic amines and sensory parameters. PMID- 27261768 TI - Isolation and characterization of Arcobacter spp. from fresh seafood and the aquatic environment. AB - Arcobacter is an emerging pathogen associated with foods of animal origin. Members of the genus Arcobacter are increasingly being isolated from fish, shellfish and the aquatic environment. In the present study, we analyzed fish, shellfish and water samples for the presence of Arcobacter spp. by conventional isolation as well as by direct PCR on the enrichment broth. Of 100 samples comprising of 42 finfish, 34 shellfish and 24 water samples analyzed, Arcobacter spp. was isolated from 8 (19%) finfish, 5 (14.7%) shellfish and 5 (20.8%) water samples. Arcobacter DNA was detected in 24 (24%) samples by direct PCR on the enrichment broth. Based on m-PCR specific to different Arcobacter spp. and 16S rRNA sequence analyses, majority (19) of the isolates were identified as Arcobacter butzleri, while two isolates were Arcobacter mytili. All Arcobacter butzleri isolates harbored putative virulence genes cadF, ciaB, mviN, pldA, tlyA and cj1349. The two isolates of A. mytili harbored mviN and cj1349 genes only. The study highlights emerging problem of the contamination of aquatic environment and fresh seafood with potentially pathogenic Arcobacter spp. PMID- 27261769 TI - Comparison between external fixation and elastic stable intramedullary nailing for the treatment of femoral shaft fractures in children younger than 8 years of age. AB - The main objective of this study was to compare external fixation (EF) with elastic stable intramedullary nailing (ESIN) for the treatment of femoral shaft fractures in children aged 8 or younger. Fifteen children with femoral shaft fractures treated by EF and 23 children with femoral shaft fractures treated by ESIN were retrospectively reviewed. All patients were pain free at the last follow-up, with good ranges of motion in the hip and knee. Partial and full weight bearing occurred sooner in patients treated with EF than with ESIN, although more polytrauma patients were present in the ESIN group. In conclusion, EF and ESIN can be considered as safe and effective methods for femoral shaft fracture treatment in children younger than 8 years of age. PMID- 27261770 TI - Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases. AB - AIMS: To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestion (RSPI). METHODS: Systematic literature review with collation and analysis of individual-level data from reported cases of RSPI associated with liver damage. RESULTS: In 199 cases meeting the selection criteria, severe liver damage (ALT/AST >=1000 IU l(-1) , liver failure or death) was reported in 186 (93%) cases including 77/78 (99%) children aged <=6 years. Liver failure occurred in 127 (64%) cases; of these 49 (39%) died. Maximum ingested daily paracetamol doses were above UK recommendations in 143 (72%) patients. US-Australasian thresholds for repeated supratherapeutic ingestions requiring intervention were not met in 71 (36%) cases; of these 35 (49%) developed liver failure and 10 (14%) died. No cases developing liver damage had paracetamol concentration < 20 mg l(-1) and a normal ALT/AST on initial presentation or when RSPI was first suspected, but both of these values were only available for 79 (40%) cases. CONCLUSIONS: Severe liver damage is reported after RSPI in adults and children, sometimes involving reported doses below current thresholds for intervention. Paracetamol concentrations <20 mg l(-1) with normal serum ALT/AST activity on initial assessment suggests a low risk of subsequent liver damage. These findings are, however, limited by low patient numbers, publication bias and the accuracy of the histories in reported cases. PMID- 27261771 TI - On methylene-bridged cysteine and lysine residues in proteins. AB - Cysteine residues ubiquitously stabilize tertiary and quaternary protein structure by formation of disulfide bridges. Here we investigate another linking interaction that involves sulfhydryl groups of cysteines, namely intra- and intermolecular methylene-bridges between cysteine and lysine residues. A number of crystal structures possessing such a linkage were identified in the Protein Data Bank. Inspection of the electron density maps and re-refinement of the nominated structures unequivocally confirmed the presence of Lys-CH2 -Cys bonds in several cases. PMID- 27261773 TI - Considerations for Completion Biopsy of Cutaneous Squamous Cell Carcinoma. PMID- 27261774 TI - Validated Assessment Scales for Decollete Wrinkling and Pigmentation. AB - BACKGROUND: Decollete aging includes skin dyspigmentation, laxity, and visible wrinkling. The development of globally accepted scales for the assessment of decollete aging is essential for aesthetic research and patient evaluation. OBJECTIVE: To develop a set of grading scales for the objective assessment of decollete aging criteria and establish the reliability and validity of these scales. MATERIALS AND METHODS: To describe age-related changes to the decollete, 3 photonumeric grading scales were created and validated: decollete wrinkles-at rest, decollete wrinkles-dynamic, and decollete pigmentation-at rest. Thirteen aesthetic experts rated photographs of the decollete of 50 women at rest and at dynamic "hand-to-elbow" positions in 2 validation sessions. Responses were analyzed to assess interrater and intrarater reliability. RESULTS: Interrater and intrarater reliability were both "almost perfect" (>=0.81, intraclass correlation coefficient and weighted kappa) for decollete wrinkles-dynamic, summary score for decollete, and estimated age. Reliability was "substantial" (0.61-0.80) for all other decollete assessments. There was high correlation between all decollete scales, estimated age, and estimated aesthetic treatment effort. CONCLUSION: Consistent outcomes between raters and by individual raters at different time points confirm the reliability of the decollete grading scales, indicating that they will be a valuable tool for use in clinical research and practice. PMID- 27261772 TI - Pesticide exposures and the risk of multiple myeloma in men: An analysis of the North American Pooled Project. AB - Multiple myeloma (MM) has been consistently linked with agricultural activities, including farming and pesticide exposures. Three case-control studies in the United States and Canada were pooled to create the North American Pooled Project (NAPP) to investigate associations between pesticide use and haematological cancer risk. This analysis used data from 547 MM cases and 2700 controls. Pesticide use was evaluated as follows: ever/never use; duration of use (years); and cumulative lifetime-days (LD) (days/year handled * years of use). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusted for age, province/state of residence, use of proxy respondents and selected medical conditions. Increased MM risk was observed for ever use of carbaryl (OR = 2.02, 95% CI = 1.28-3.21), captan (OR = 1.98, 95% CI = 1.04-3.77) and DDT (OR = 1.44, 95% CI = 1.05-1.97). Using the Canadian subset of NAPP data, we observed a more than threefold increase in MM risk (OR = 3.18, 95% CI = 1.40 7.23) for <=10 cumulative LD of carbaryl use. The association was attenuated but remained significant for >10 LD of carbaryl use (OR = 2.44; 95% CI = 1.05-5.64; ptrend = 0.01). For captan, <=17.5 LD of exposure was also associated with a more than threefold increase in risk (OR = 3.52, 95% CI = 1.32-9.34), but this association was attenuated in the highest exposure category of >17.5 LD (OR = 2.29, 95% CI = 0.81-6.43; ptrend = 0.01). An increasing trend (ptrend = 0.04) was observed for LD of DDT use (LD > 22; OR = 1.92, 95% CI = 0.95-3.88). In this large North American study of MM and pesticide use, we observed significant increases in MM risk for use of carbaryl, captan and DDT. PMID- 27261775 TI - Complex Regional Pain Syndrome After Nail Surgery. PMID- 27261776 TI - Activation of proteinase 3 contributes to Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance. AB - Activation of inflammatory pathways is known to accompany development of obesity induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro inflammatory mediators IL-1beta and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential. PMID- 27261777 TI - Body Mass Index and Risk for Mental Stress Induced Ischemia in Coronary Artery Disease. AB - Acute emotionally reactive mental stress (MS) can provoke prognostically relevant deficits in cardiac function and myocardial perfusion, and chronic inflammation increases risk for this ischemic phenomenon. We have described parasympathetic withdrawal and generation of inflammatory factors in MS. Adiposity is also associated with elevated markers of chronic inflammation. High body mass index (BMI) is frequently used as a surrogate for assessment of excess adiposity, and associated with traditional CAD risk factors, and CAD mortality. BMI is also associated with autonomic dysregulation, adipose tissue derived proinflammatory cytokines, which are also attendant to emotion provoked myocardial ischemia. Thus, we sought to determine if body mass index (BMI) contributes to risk of developing myocardial ischemia provoked by mental stress. We performed a prospective interventional study in a cohort of 161 patients with stable CAD. They completed an assessment of myocardial blood flow with single photon emission computed tomography (SPECT) simultaneously during 2 conditions: laboratory mental stress and at rest. Multivariate logistic regression determined the independent contribution of BMI to the occurrence of mental-stress induced ischemia. Mean age was 65.6 +/-9.0 years; 87.0% had a history of hypertension, and 28.6% had diabetes. Mean BMI was 30.4 +/- 4.7. Prevalence of mental stress ischemia was 39.8%. BMI was an independent predictor of mental stress ischemia, OR=1.10, 95% CI [1.01-1.18] for one-point increase in BMI and OR=1.53, 95% CI [1.06-2.21] for a 4.7 point increase in BMI (one standard deviation beyond the cohort BMI mean), p=0.025 for all. These data suggest that BMI may serve as an independent risk marker for mental stress ischemia. The factors attendant with greater BMI, which include autonomic dysregulation and inflammation, may represent pathways by which high BMI contribute to this risk and serve as a conceptual construct to replicate these findings in larger CAD populations. PMID- 27261778 TI - Receptor-mediated reticulophagy: a novel promising therapy target for diseases. PMID- 27261779 TI - Short-term serum deprivation causes no significant mitochondrial DNA mutation in vascular smooth muscle cells revealed by a new next generation sequencing technology. PMID- 27261780 TI - Formaldehyde accelerates cellular senescence in HT22 cells: possible involvement of the leptin pathway. PMID- 27261781 TI - Plant-Microbiota Interactions as a Driver of the Mineral Turnover in the Rhizosphere. AB - A major challenge facing agriculture in the 21st century is the need to increase the productivity of cultivated land while reducing the environmentally harmful consequences of mineral fertilization. The microorganisms thriving in association and interacting with plant roots, the plant microbiota, represent a potential resource of plant probiotic function, capable of conjugating crop productivity with sustainable management in agroecosystems. However, a limited knowledge of the organismal interactions occurring at the root-soil interface is currently hampering the development and use of beneficial plant-microbiota interactions in agriculture. Therefore, a comprehensive understanding of the recruitment cues of the plant microbiota and the molecular basis of nutrient turnover in the rhizosphere will be required to move toward efficient and sustainable crop nutrition. In this chapter, we will discuss recent insights into plant-microbiota interactions at the root-soil interface, illustrate the processes driving mineral dynamics in soil, and propose experimental avenues to further integrate the metabolic potential of the plant microbiota into crop management and breeding strategies for sustainable agricultural production. PMID- 27261782 TI - Familiar Stranger: Ecological Genomics of the Model Saprotroph and Industrial Enzyme Producer Trichoderma reesei Breaks the Stereotypes. AB - The filamentous fungus Trichoderma reesei (Hypocreales, Ascomycota) has properties of an efficient cell factory for protein production that is exploited by the enzyme industry, particularly with respect to cellulase and hemicellulase formation. Under conditions of industrial fermentations it yields more than 100g secreted protein L(-1). Consequently, T. reesei has been intensively studied in the 20th century. Most of these investigations focused on the biochemical characteristics of its cellulases and hemicellulases, on the improvement of their properties by protein engineering, and on enhanced enzyme production by recombinant strategies. However, as the fungus is rare in nature, its ecology remained unknown. The breakthrough in the understanding of the fundamental biology of T. reesei only happened during 2000s-2010s. In this review, we compile the current knowledge on T. reesei ecology, physiology, and genomics to present a holistic view on the natural behavior of the organism. This is not only critical for science-driven further improvement of the biotechnological applications of this fungus, but also renders T. reesei as an attractive model of filamentous fungi with superior saprotrophic abilities. PMID- 27261783 TI - Analysis of Low-Biomass Microbial Communities in the Deep Biosphere. AB - Over the past few decades, the subseafloor biosphere has been explored by scientific ocean drilling to depths of about 2.5km below the seafloor. Although organic-rich anaerobic sedimentary habitats in the ocean margins harbor large numbers of microbial cells, microbial populations in ultraoligotrophic aerobic sedimentary habitats in the open ocean gyres are several orders of magnitude less abundant. Despite advances in cultivation-independent molecular ecological techniques, exploring the low-biomass environment remains technologically challenging, especially in the deep subseafloor biosphere. Reviewing the historical background of deep-biosphere analytical methods, the importance of obtaining clean samples and tracing contamination, as well as methods for detecting microbial life, technological aspects of molecular microbiology, and detecting subseafloor metabolic activity will be discussed. PMID- 27261784 TI - The Impact of Oxygen on Bacterial Enteric Pathogens. AB - Bacterial enteric pathogens are responsible for a tremendous amount of foodborne illnesses every year through the consumption of contaminated food products. During their transit from contaminated food sources to the host gastrointestinal tract, these pathogens are exposed and must adapt to fluctuating oxygen levels to successfully colonize the host and cause diseases. However, the majority of enteric infection research has been conducted under aerobic conditions. To raise awareness of the importance in understanding the impact of oxygen, or lack of oxygen, on enteric pathogenesis, we describe in this review the metabolic and physiological responses of nine bacterial enteric pathogens exposed to environments with different oxygen levels. We further discuss the effects of oxygen levels on virulence regulation to establish potential connections between metabolic adaptations and bacterial pathogenesis. While not providing an exhaustive list of all bacterial pathogens, we highlight key differences and similarities among nine facultative anaerobic and microaerobic pathogens in this review to argue for a more in-depth understanding of the diverse impact oxygen levels have on enteric pathogenesis. PMID- 27261785 TI - Urologic Emergencies. AB - The diagnosis and management of urologic emergencies are incorporated into the basic training of all urology residents. In institutions without access to urologic services, it is usually left to the General Surgeon or Emergency Medicine physician to provide timely care. This article discusses diagnoses that are important to recognize and treatment that is practically meaningful for the non-Urologist to identify and treat. The non-Urology provider, after reading this article, will have a better understanding and a higher comfort level with treating patients with urologic emergencies. PMID- 27261786 TI - Surgical Management of Urologic Trauma and Iatrogenic Injuries. AB - Genitourinary trauma usually occurs in the setting of multisystem trauma, accounting for approximately 10% of all emergency department admissions. Timely evaluation and management of the trauma patient have the potential to minimize urologic morbidity and mortality. New imaging modalities and a growing emphasis on nonoperative expectant management of both upper and lower urinary tract injuries have changed the field of urologic trauma. Concomitant injury to both the upper and the lower urinary tract is rare, but careful evaluation is critical to identify these devastating injuries. PMID- 27261787 TI - Diagnosis and Management of Lower Urinary Tract Dysfunction. AB - Lower urinary tract dysfunction is an umbrella diagnosis that covers difficulty evacuating urine from the bladder. In its most simple form, it is either an inability to store urine or an inability to empty the bladder of urine appropriately. The normal and the abnormal bladder, the role of urodynamics in evaluation of lower urinary tract dysfunction, and the medical and behavioral management of some of these disorders are reviewed. PMID- 27261788 TI - Urinary Retention in Surgical Patients. AB - Urinary retention is an important and potentially avoidable postoperative complication. Identifying risk factors for retention is important given expedient bladder decompression is important for long-term outcomes. Age, benign prostatic hyperplasia, and lower urinary tract symptoms are patient factors that predispose to retention. Surgery-related factors include operative time, intravenous fluid administration, type of anesthesia, and procedure type. The mainstay for treatment in the acute setting is Foley catheter placement. Starting alpha blockers in men is also indicated as they increase voiding trial success. Long term solutions for chronic retention include a variety of surgeries, with transurethral prostatectomy as the gold standard. PMID- 27261789 TI - Surgical Management of Female Voiding Dysfunction. AB - Surgical intervention for female voiding dysfunction is common, involving a single or multifaceted approach affecting multiple organ systems in the pelvis. Surgical success relies on knowledge of surgical history, anatomic approaches, and judicious use of supports or materials. Owing to the varied repairs used over the last few decades, it is important for the general surgeon to understand both current and historic approaches. This understanding will help in planning future pelvic surgery as well as in evaluating current ramifications of prior surgery. PMID- 27261790 TI - Surgical Management of Male Voiding Dysfunction. AB - Benign prostatic hypertrophy (BPH) is a common cause of voiding dysfunction. BPH may lead to bladder outlet obstruction and resultant troublesome lower urinary tract symptoms. Initial management of BPH and bladder outlet obstruction is typically conservative. However, when symptoms are severe or refractory to medical therapy or when urinary retention, bladder stone formation, recurrent urinary tract infections, or upper urinary tract deterioration occur, surgical intervention is often necessary. Numerous options are available for surgical management of BPH ranging from simple office-based procedures to transurethral operative procedures and even open and robotic surgeries. This article reviews the current, most commonly used techniques available for surgical management of BPH. PMID- 27261791 TI - Diagnosis and Management of Hematuria. AB - Microscopic and gross hematuria present unique and difficult diagnostic and management challenges in the already complex general surgery patient. This article provides the general surgeon with relevant knowledge in the pathophysiology, anatomy, etiologies, workup, and treatments of hematuria. In addition common causes of hematuria that may be encountered by the general surgeon (including trauma, urinary tract infection, urolithiasis, and malignancy), the difficult to manage clinical situation of clot urinary retention is presented. This article provides a urologic framework of thinking for the clinician to best manage a general surgery patient who has hematuria. PMID- 27261792 TI - Diagnosis and Management of Nephrolithiasis. AB - Nephrolithiasis is a common affliction, affecting approximately 10% of adults. Potentially presenting with acute abdominal or flank pain, nausea, or emesis, it may pose as a general surgical condition. Therefore, recognition, diagnosis, and management concerns are pertinent to the general surgeon. Furthermore, the risk of nephrolithiasis is increased in common general surgical conditions, including inflammatory bowel disease, hyperparathyroidism, and short gut. Nephrolithiasis may be induced as a result of general surgical interventions, including gastric bypass and bowel resection with ileostomy. An understanding of this common disease will improve coordination of patient care between urologists and general surgeons. PMID- 27261793 TI - Genitourinary Prosthetics: A Primer for the Non-urologic Surgeon. AB - Genitourinary prosthetics are used for correction of functional deficits and to improve the quality of lives of affected patients. General surgeons must evaluate patients scheduled for nonurologic surgery with urologic devices that can impact their perioperative management. Lack of recognition of these prosthetics preoperatively can lead to unnecessary morbidity for the patient and have legal implications for the surgeon. Close consultation with a urologist may avoid common complications associated with these devices and allows for surgical assistance when operative misadventures do occur. This article reviews 3 common urologic prosthetics: testicular prosthesis, artificial urinary sphincter, and penile prosthesis. PMID- 27261794 TI - Pediatric Urology for the General Surgeon. AB - Pediatric urology spans the neonatal period through the transition into early adulthood. There are a variety of common pediatric urologic conditions that overlap significantly with pediatric surgery. This article reviews the pertinent pathophysiology of a few key disease processes, including the pediatric inguinal hernia and/or hydrocele, cryptorchidism, and circumcision. General surgeons may find themselves in the position of managing these problems primarily, particularly in rural areas that may lack pediatric subspecialization. An understanding of the fundamentals can guide appropriate initial management. Additional focus is devoted to the management of genitourinary trauma to guide the general surgeon in more acute, emergent settings. PMID- 27261795 TI - The Use of Bowel in Urologic Reconstructive Surgery. AB - Intestinal surgery involves an operative space shared by both general surgeons and urologists and is a border region where these 2 surgical disciplines often intersect. Urologists routinely use both small and large bowel for reconstructive procedures and surgeons often encounter such reconstructions of the urinary tract. It is essential for surgeons to understand the urologic indications for using intestinal segments for reconstructive procedures, the variety of such reconstructions, the anatomic landmarks and potential pitfalls that should be considered when intraoperatively encountering such reconstructions, and the potential metabolic consequences of the incorporation of bowel segments into the urinary collecting system. PMID- 27261796 TI - Diagnosis and Surgical Management of Uroenteric Fistula. AB - Uroenteric fistulae can occur between any part of the urinary tract and the small and large bowel. Classification is generally based on the organ of origin in the urinary tract and the termination of the fistula in the segment of the gastrointestinal tract. Surgery is often necessary. Congenital fistulae are rare, with most being acquired. Uroenteric fistulae most frequently occur in a setting of inflammatory bowel disease. Imaging often helps in the diagnosis. Management of urinary fistulae includes adequate nutrition, diversion of the urinary tract, diversion of the gastrointestinal tract, treatment of underling inflammatory process or malignancy, and surgery. PMID- 27261797 TI - Diagnosis and Surgical Management of Male Pelvic, Inguinal, and Testicular Pain. AB - Pain occurs in the male genitourinary organs as for any organ system in response to traumatic, infectious, or irritative stimuli. A knowledge and understanding of chronic genitourinary pain can be of great utility to practicing nonurologists. This article provides insight into the medical and surgical management of subacute and chronic pelvic, inguinal, and scrotal pain. The pathophysiology, diagnosis, and medical and surgical treatment options of each are discussed. PMID- 27261798 TI - Robotic Surgery of the Kidney, Bladder, and Prostate. AB - Robot-assisted surgery offers the advantages of a minimally invasive approach with greater technical ease and a shorter learning curve than pure laparoscopy. Fueled by the success of the robot-assisted laparoscopic prostatectomy, urologists are increasingly using the robotic platform for other advanced operations involving the kidney, ureters, bladder, and prostate. Robotic surgery has been shown to be safe and effective, with good perioperative, functional, and oncologic outcomes. Although cost continues to be a major concern regarding the use of robotic technology, improved efficiency and reduced hospital stays associated with the minimally invasive approach are allowing for better cost effectiveness. PMID- 27261799 TI - Foreword. PMID- 27261800 TI - Preface. PMID- 27261801 TI - Characteristic CT and MR imaging findings of cerebral paragonimiasis. AB - BACKGROUND AND PURPOSE: The early diagnosis of cerebral paragonimiasis (CP) is essential for a good prognosis. We seek to provide references for early diagnosis by analyzing the imaging characteristics of cerebral paragonimiasis. MATERIALS AND METHODS: Images of 27 patients with CP (22 males and 5 females; median age 20.3 years; range: 4 to 47 years) were retrospectively evaluated. All patients underwent head computed tomography (CT) scans; 22 patients underwent conventional magnetic resonance imaging (MRI) sequences, including contrast-enhanced MRI for 20 patients and diffusion-weighted-imaging (DWI) for 1 patient. The diagnosis was confirmed based on a positive antibody test using enzyme-linked immunosorbent assay (ELISA) for paragonimiasis in the serum. RESULTS: The most common imaging findings of CP were isodense or hypodense lesions combined with extensive hypodense areas of perilesional edema on CT scans and a large mass composed of multiple ring-shaped lesions with surrounding edema on MRI images. The conglomeration of multiple ring-shaped lesions (n=11 patients), "tunnel signs" (n=12 patients) and worm-eaten signs (n=5 patients) were characteristic of most CP images. In 14 patients, contrast-enhanced MRI showed varying degrees of contrast enhancement combined with adjacent meningeal enhancement (n=10). CONCLUSIONS: A large mass comprising multiple ring-shaped lesions of different sizes, "tunnel signs" and worm-eaten signs with surrounding edema are the most characteristic features of CP. Extensive invasions of the adjacent meninges and ventricular wall (19 patients), multiple intracerebral lesions, bilateral hemispheric involvement, and lesion migration are other noteworthy imaging characteristics. PMID- 27261802 TI - Controversies and Trends in United Kingdom Bunion Surgery. AB - Current practice and controversies in UK bunion surgery are discussed. Patients tend to be offered a distally based metatarsal osteotomy, such as a chevron or scarf osteotomy, for mild to moderate symptomatic bunions. Greater deformities are managed with a more extreme scarf, supplemented with a proximal phalangeal osteotomy. A proximal fusion in the form of the Lapidus-type procedure is still reserved for the most severe, hypermobile, or arthritic cases. Minimally invasive techniques for bunions have failed to disseminate into common UK practice. The trends in the United Kingdom regarding litigation, venous thromboembolism, and osteodesis for bunion surgery are also discussed. PMID- 27261804 TI - Recent Advances in Foot and Ankle Surgery in Mainland China: Correction of Severe Foot and Ankle Deformities. AB - Foot and ankle physicians in China encounter quite a large amount of severe and complex deformities. The main cause of severe ankle and foot deformity is trauma, while the other causes may be neuromuscular diseases, improper reduction and fixation and so on. Staged procedure may sometimes be a safer way to correct deformities in the presence of severe soft tissue contracture. Periarticular osteotomy combined with soft tissue balancing can be used in treating severe varus ankle arthritis, including stage IIIb cases and patients with talar tilt of more than 10 degrees. PMID- 27261803 TI - What's New in Severe Deformity Correction: The German Perspective. AB - Foot deformities are found in several neurologic conditions, most typically, but not exclusively, Charcot-Marie-Tooth disease. Posttraumatic deformities and undercorrection or overcorrection of congenital talipes equinovarus are also encountered. A severely deformed foot that cannot fit into normal shoes presents a significant day-to-day challenge to the young and active patient. This article presents some basic principles for evaluating the deformity and a toolkit of procedures to deal with these complex cases. PMID- 27261805 TI - Total Toe Replacement in the United States: What Is Known and What Is on the Horizon. AB - Arthritis of the first metatarsophalangeal is a common problem of the forefoot. The gold standard surgical treatment has been fusion of the first metatarsophalangeal joint. Many patients are unwilling to accept pain relief at the expense of loss of motion and the corresponding loss of shoe wear choices and activities requiring dorsiflexion of the hallux. Early implants were plagued with loosening and continued pain but implants have evolved. Current implants use modern bearing surfaces with press-fit fixation. These implants have renewed optimism for total toe arthroplasty. This article reviews the literature for implants currently available and describes the surgical techniques. PMID- 27261806 TI - Total Ankle Arthroplasty: An Overview of the Canadian Experience. AB - Total ankle arthroplasty use has increased across Canada over the last two decades. Multiple implant designs are readily available and implanted across Canada. Although arthrodesis is a reliable procedure for treating end-stage ankle arthritis, ankle replacement is often the preferred surgical treatment by patients. A recent prospective study evaluated intermediate-term outcomes of ankle replacement and arthrodesis at multiple centers across Canada, with variability in prosthesis type, surgeon, and surgical technique. Intermediate term clinical outcomes of total ankle replacement and ankle arthrodesis were comparable in a diverse cohort in which treatment was tailored to patient presentation; however, rates of reoperation and major complications were higher after ankle replacement. PMID- 27261807 TI - Sports Medicine and Arthroscopic Treatment of the Foot and Ankle: What Is New and Current in Singapore. AB - Foot and ankle abnormalities are common in Singapore because of the compulsory conscription, the slipper-wearing culture, and the promotion of healthy living through exercise. The rapidly aging population, lack of elite sportsmen, and social and cultural norms pose unique challenges to foot and ankle surgery. Orthopedic surgery in Singapore has progressed because of the good infrastructure and modern practices executed by fellowship-trained surgeons. Evolving local practices are polarized by practice trends emulated from North America and Europe. The small community of foot and ankle surgeons currently practicing in Singapore allows for easier communication, corroborative educational events, and research initiatives. PMID- 27261808 TI - My Experience as a Foot and Ankle Trauma Surgeon in Montreal, Canada: What's Not in the Books. AB - Foot and ankle fractures are sometimes seen as routine and easy to treat. However, many fractures vary from typical patterns and require more complex management. Obtaining good outcomes in these situations can be challenging. Often, the difference between average and good results has to do with preoperative planning and good surgical technique. This article outlines numerous techniques and tricks that are not always mentioned in classic textbooks. It focuses on ankle, talus, calcaneus, and midfoot fractures, and discusses numerous techniques and aids to avoid potential problems that may be encountered intraoperatively. PMID- 27261809 TI - Current Swiss Techniques in Management of Lisfranc Injuries of the Foot. AB - The outcome after Lisfranc injuries correlates with anatomic and stable reduction. The best surgical treatment, particularly for the ligamentous Lisfranc injuries, remains controversial. Recent publications suggest that the ligamentous injuries may benefit from primary partial Lisfranc arthrodesis. Most surgeons agree that an appropriate reduction is better and easier achieved by open reduction and stable temporary screw or dorsal plate fixation or by open primary partial arthrodesis than by closed reduction or Kirschner wire fixation. Despite correct surgical technique and postoperative management, symptom-free recovery is uncommon. This article outlines current techniques in the management of Lisfranc injuries and resultant postoperative outcomes in a level I trauma center. PMID- 27261810 TI - Minimally Invasive Forefoot Surgery in France. AB - Study groups have been formed in France to advance the use of minimally invasive surgery. These techniques are becoming more frequently used and the technique nuances are continuing to evolve. The objective of this article was to advance the awareness of the current trends in minimally invasive surgery for common diseases of the forefoot. The percutaneous surgery at the forefoot is less developed at this time, but also will be discussed. PMID- 27261811 TI - State-of-the-Art in Ankle Fracture Management in Chile. AB - The ankle represents the most commonly injured weightbearing joint in the human body. They are typically the result of low-energy, rotational injury mechanisms. However, ankle fractures represent a spectrum of injury patterns from simple to very complex, with varying incidence of posttraumatic arthritis. Stable injury patterns can be treated nonoperatively; unstable injury patterns are typically treated operatively given that they could lead to severe arthritis if not properly addressed. PMID- 27261812 TI - Foot and Ankle Injuries in Professional Soccer Players: Diagnosis, Treatment, and Expectations. AB - Soccer is one of the most popular sports in the world. It has undergone many changes in recent years, mainly because of increased physical demands, and this has led to an increased injury risk. Direct contact accounts for half of all injuries in both indoor and outdoor soccer and ankle sprains are the most common foot and ankle injury. There is a spectrum of foot and ankle injuries and their treatment should be individualized in these high-demand patients. An injury prevention program is also important and should the players, the trainer, responsible physician, and physical therapists. PMID- 27261813 TI - Recent Advances in Egypt for Treatment of Talar Osteochondral Lesions. AB - Treatment of osteochondral defects (OCLs) of the talus is a challenging orthopedic surgery. Treatment of talar OCLs has evolved through the 3 "R" paradigm: reconstruction, repair, and replacement. This article highlights current state-of-the-art techniques and reviews recent advances in the literature about articular cartilage repair using various novel tissue engineering approaches, including various scaffolds, growth factors, and cell niches; which include chondrocytes and culture-expanded bone marrow-derived mesenchymal stem cells. PMID- 27261814 TI - Preface. PMID- 27261815 TI - Single-molecule detection and tracking of RNA transcripts in living cells using phosphorothioate-optimized 2'-O-methyl RNA molecular beacons. AB - Molecular Beacons (MBs) composed of 2'-O-methyl RNA (2Me) and phosphorothioate (PS) linkages throughout the backbone (2Me/PSFULL MBs) have enabled long-term imaging of RNA in living cells, but excess PS modification can induce nonspecific binding, causing false-positive signals. In this study, we evaluate the intracellular stability of MBs composed of 2Me with various PS modifications, and found that false-positive signals could be reduced to marginal levels when the MBs possess a fully PS-modified loop domain and a phosphodiester stem (2Me/PSLOOP MB). Additionally, 2Me/PSLOOP MBs exhibited uncompromised hybridization kinetics, prolonged functionality and >88% detection accuracy for single RNA transcripts, and could do so without interfering with gene expression or cell growth. Finally, 2Me/PSLOOP MBs could image the dynamics of single mRNA transcripts in the nucleus and the cytoplasm simultaneously, regardless of whether the MBs targeted the 5'- or the 3'-UTR. Together, these findings demonstrate the effectiveness of loop domain PS modification in reducing nonspecific signals and the potential for sensitive and accurate imaging of individual RNAs at the single-molecule level. With the growing interest in the role of RNA localization and dynamics in health and disease, 2Me/PSLOOP MBs could enable new discoveries in RNA research. PMID- 27261816 TI - Obstetric and neonatal outcome following minor trauma in pregnancy. Is hospitalization warranted? AB - OBJECTIVE: To evaluate if hospitalization of pregnant women, involved in minor trauma, for 24h of surveillance, is warranted. STUDY DESIGN: The medical files of pregnant women involved in minor trauma, during 2009-2014, at 22-42 gestational weeks, were reviewed. Minor trauma was defined as an injury severity score <3, no immediate complains, normal ultrasound evaluation, reactive non-stress test, and no regular contractions. Patients were divided into those who, according to our departmental protocol, were hospitalized for 24h observation (hospitalized group), and those who refused to be hospitalized, (non-hospitalized group). Pregnancy, delivery and neonatal outcomes were compared between the groups. RESULTS: Included in the study were 946 minor trauma patients that met the inclusion criteria. Gestational age (GA) at the trauma event was lower in the non hospitalized group (n=331) compared to the hospitalized group (n=615), 29.1 vs. 30.8 weeks, p<0.001, respectively. There were no between-groups differences in the rate of preterm birth, vaginal bleeding, GA at delivery, or cesarean delivery. There were no cases of placental abruption or intrauterine fetal death in both groups. Neonatal outcome did not differ between the groups. CONCLUSION: Minor trauma during pregnancy, with normal initial assessment, is not associated with adverse pregnancy outcomes. Therefore, routine hospitalization is probably not warranted. PMID- 27261817 TI - Efficacy, tolerability and safety of a new medical device, Monurelle Biogel((r)) vaginal gel, in the treatment of vaginal dryness: a randomized clinical trial in women of reproductive age. AB - OBJECTIVE: To prove the efficacy, tolerability and safety of Monurelle Biogel((r)) (ZP-025) vaginal gel, which contains a purified, dialyzed, lyophilized bovine colostrum, in women of reproductive age suffering from vaginal dryness. DESIGN: Randomized clinical trial (RCT) (Z7213M01). SETTING: Five University Gynaecological Units. PATIENTS: Ninety-five subjects were allocated at random to receive either ZP-025 (n=48) for about 23 intermenstrual days (1 or 2 times/daily intra-vaginally) or no treatment (lubricants on demand were allowed). MAIN OUTCOME MEASURES: Change of Verbal Rating Scale (VRS) total and single score for vaginal symptoms, Vaginal Health Index (VHI) score, Female Sexual Function index (FSFI) and Female Sexual Distress Scale-revised (FSDS-R) scores. RESULTS: A total number of 85 subjects was evaluable for primary analyses. Symptoms (VRS) of vaginal discomfort improved significantly already after 11 days, as compared to the control arm (p<0.0001). The mean VHI score was also significantly higher in ZP-025 group (p<0.001) at the end of the study. The analysis of covariance with the baseline value as covariate carried out on the FSFI Total Score showed a statistically significant difference in favour of the ZP-025 arm (p<0.032). A shift from presence to absence of sexual distress (<=11 points) was more prominent in the ZP-025 arm [10 subjects (40%) in the ZP-025 arm (p<0.0001) and 6 subjects (21.4%) in the control arm (p=0.01)]. Women reported a compliance rate of 100% for one ZP-025 application/day. Local tolerability of ZP-025 was excellent or good in 82.9% of the subjects. CONCLUSIONS: The present multicentre RCT supports the use of Monurelle Biogel((r)) in women of reproductive age reporting symptoms of vaginal dryness. A positive impact on vaginal health and sexual function was also evident. PMID- 27261818 TI - The association between a low cerebro-umbilical ratio at 30-34 weeks gestation, increased intrapartum operative intervention and adverse perinatal outcomes. AB - INTRODUCTION: The aim of this study was to investigate the relationship between the cerebro-umbilical ratio (CUR), measured at 30-34 weeks, and adverse intrapartum and perinatal outcomes. METHODS: This was a retrospective cross sectional cohort study of women delivering at the Mater Mothers' Hospital in Brisbane, Australia. Fetal Doppler indices for 1224 singleton pregnancies were correlated with maternal demographics and intrapartum and perinatal outcomes. Only women who attempted vaginal delivery were included in the study. RESULTS: Infants delivered by emergency cesarean section for fetal compromise had the lowest median CUR, 1.65 (IQR 1.17-2.12), compared to any other delivery group. The proportion of infants with a CUR <=1 who required emergency cesarean section for fetal compromise was 33.3% compared to 9.3% of infants with a CUR >1 (adjusted OR 6.92 (95% CI 2.04-25.75), p<0.001). However, the detection rate of CUR <=1 as a predictor for emergency cesarean delivery for fetal compromise was poor (18.9%). Detection rates increased in cohorts of infants born within two weeks of the scan or with birth weights <10th centile or <5th centile. Additionally, a CUR <=1 was associated with lower median birth weight, higher rates of admission to the neonatal critical care unit and increased neonatal mortality. DISCUSSION: This study suggests that a CUR <=1, measured at 30-34 weeks, is associated with a greater risk of emergency cesarean delivery for fetal compromise and a number of other adverse perinatal outcomes. The association was strongest in low birth weight babies. PMID- 27261819 TI - Analysis of the cell-free amniotic fluid transcriptome expressed during the euploid mid-trimester of pregnancy. AB - OBJECTIVE: The amniotic fluid (AF) contains cell-free RNAs (cfRNAs), which are considered to reflect the fetal status in utero. However, there are limited numbers of data to examine the AF cell-free transcriptome because amniocentesis is an invasive procedure. In this study, the AF transcriptome expressed during the euploid mid-trimester of pregnancy was characterized. STUDY DESIGN: Fourteen AF samples were collected. RNA was extracted from AF supernatant, hybridized to Affymetrix GeneChip Human arrays, and the transcriptome was analyzed by using the DAVID toolkit. RESULT: We detected 1069 genes in the 14 AF samples. The GNF atlas mapping showed that genes present in the AF were annotated with endocrine organs and blood components, including the pancreas, adrenal gland, thyroid, ovary and monocytes. The proteins encoded by the transcriptome were localized to several organs, which are directly in contact with the AF, including the placenta, lung, skin, epithelium, and kidney. During the early fetal period, there is a bi directional diffusion between the fetus and AF. Therefore, the AF composition is similar to that of the fetal plasma. In addition, fetal urine, swallowing, pulmonary secretion, and diffusion across the placenta contribute to produce amniotic fluid by directly excreting fluid. The KEGG pathway analysis with placenta specific genes revealed that focal adhesion and extracellular matrix receptor interaction pathways were enriched. These pathways are important for the placental development. CONCLUSION: cfRNA in the amniotic fluid originates from placenta and fetal organs directly contacting the amniotic fluid as well as from diffusion of the fetal plasma across the placenta. AF transcriptome may reflect not only fetal development, but also placental development. PMID- 27261820 TI - Molecular Basis of Functional Myocardial Potassium Channel Diversity. AB - Multiple types of voltage-gated K(+) and non-voltage-gated K(+) currents have been distinguished in mammalian cardiac myocytes based on differences in time dependent and voltage-dependent properties and pharmacologic sensitivities. Many of the genes encoding voltage-gated K(+) (Kv) and non-voltage-gated K(+) (Kir and K2P) channel pore-forming and accessory subunits are expressed in the heart, and a variety of approaches have been, and continue to be, used to define the molecular determinants of native cardiac K(+) channels and to explore the molecular mechanisms controlling the diversity, regulation, and remodeling of these channels in the normal and diseased myocardium. PMID- 27261822 TI - Genetic Control of Potassium Channels. AB - Approximately 80 genes in the human genome code for pore-forming subunits of potassium (K(+)) channels. Rare variants (mutations) in K(+) channel-encoding genes may cause heritable arrhythmia syndromes. Not all rare variants in K(+) channel-encoding genes are necessarily disease-causing mutations. Common variants in K(+) channel-encoding genes are increasingly recognized as modifiers of phenotype in heritable arrhythmia syndromes and in the general population. Although difficult, distinguishing pathogenic variants from benign variants is of utmost importance to avoid false designations of genetic variants as disease causing mutations. PMID- 27261821 TI - Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology. AB - Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. PMID- 27261825 TI - Potassium Channel Remodeling in Heart Disease. AB - Heart disease produces substantial remodeling of K(+) channels that in general promotes arrhythmia occurrence. In the case of ventricular arrhythmias, K(+) channel remodeling contributes to the arrhythmic risk and increases vulnerability to torsades de pointes with K(+) channel inhibiting drugs. Atrial K(+) channel remodeling caused by atrial fibrillation promotes arrhythmia stability and presents opportunities for the development of new drugs targeting atrial inward rectifier K(+) currents. A better understanding of K(+) channel remodeling will help clinicians to appreciate arrhythmia mechanisms and determinants in a variety of clinical situations and to better manage arrhythmia therapy in patients with heart disease. PMID- 27261823 TI - Cardiac Delayed Rectifier Potassium Channels in Health and Disease. AB - Cardiac delayed rectifier potassium channels conduct outward potassium currents during the plateau phase of action potentials and play pivotal roles in cardiac repolarization. These include IKs, IKr and the atrial specific IKur channels. In this article, we will review their molecular identities and biophysical properties. Mutations in the genes encoding delayed rectifiers lead to loss- or gain-of-function phenotypes, disrupt normal cardiac repolarization and result in various cardiac rhythm disorders, including congenital Long QT Syndrome, Short QT Syndrome and familial atrial fibrillation. We will also discuss the prospect of using delayed rectifier channels as therapeutic targets to manage cardiac arrhythmia. PMID- 27261824 TI - Adenosine Triphosphate-Sensitive Potassium Currents in Heart Disease and Cardioprotection. AB - The subunit makeup of the family of adenosine triphosphate-sensitive potassium channel (KATP) channels is more complex and labile than thought. The growing association of Kir6.1 and SUR2 variants with specific cardiovascular electrical and contractile derangements and the clear association with Cantu syndrome establish the importance of appropriate activity in normal function of the heart and vasculature. Further studies of such patients will reveal new mutations in KATP subunits and perhaps in proteins that regulate KATP synthesis, trafficking, or location, all of which may ultimately benefit therapeutically from the unique pharmacology of KATP channels. PMID- 27261827 TI - Clinical Features of Genetic Cardiac Diseases Related to Potassium Channelopathies. AB - Genetic cardiac diseases related to potassium channelopathies are a group of relatively rare syndromes that includes long QT syndrome, short QT syndrome, Brugada syndrome, and early repolarization syndrome. Patients with these syndromes share a propensity for the development of life-threatening ventricular arrhythmias in the absence of significant cardiac structural abnormalities. Familial atrial fibrillation has also been associated with potassium channel dysfunction but differs from the other syndromes by being a rare cause of a common condition. This article focuses on the clinical features, diagnosis, and management of these syndromes. PMID- 27261826 TI - Modulation of Cardiac Potassium Current by Neural Tone and Ischemia. AB - The cardiac action potential is generated by intricate flows of ions across myocyte cell membranes in a coordinated fashion to control myocardial contraction and the heart rhythm. Modulation of the flow of these ions in response to a variety of stimuli results in changes to the action potential. Abnormal or altered ion currents can result in cardiac arrhythmias. Abnormalities of autonomic regulation of potassium current play a role in the genesis of cardiac arrhythmias, and alterations in acetylcholine-activated potassium channels may play a key role in atrial fibrillation. Ischemia is another important modulator of cardiac cellular electrophysiology. PMID- 27261828 TI - Potassium Channel Block and Novel Autoimmune-Associated Long QT Syndrome. AB - This article reviews advances in the pathogenesis of anti-SSA/Ro antibody-induced corrected QT (QTc) prolongation in patients with autoimmune diseases; particularly connective tissue disease (CTD). Evidence shows that anti-SSA/Ro antibody-positive patients with CTD show QTc prolongation and complex ventricular arrhythmias. Molecular and functional data provide evidence that the human ether a-go-go-related gene potassium channel conducting the rapidly activating delayed rectifier potassium current is directly inhibited by anti-SSA/Ro antibodies, resulting in action potential duration prolongation leading to QT interval lengthening. Routine electrocardiogram screening in anti-SSA/Ro antibody-positive patients and counseling for patients with other QTc prolonging risk factors is recommended. PMID- 27261830 TI - Mechanism of Proarrhythmic Effects of Potassium Channel Blockers. AB - Any disturbance of electrical impulse formation in the heart and of impulse conduction or action potential (AP) repolarization can lead to rhythm disorders. Potassium (K(+)) channels play a prominent role in the AP repolarization process. In this review we describe the causes and mechanisms of proarrhythmic effects that arise as a response to blockers of cardiac K(+) channels. The largest and chemically most diverse groups of compound targets are Kv11.1 (hERG) and Kv7.1 (KvLQT1) channels. Finally, the proarrhythmic propensity of atrial-selective K(+) blockers inhibiting Kv1.5, Kir3.1/3.4, SK, and K2P channels is discussed. PMID- 27261829 TI - Pharmacogenetics of Potassium Channel Blockers. AB - The QT interval on surface electrocardiograms provides a model of a multicomponent integrated readout of many biological systems, including ion channels, modulatory subunits, signaling systems that modulate their activity, and mechanisms that regulate the expression of their responsible genes. The problem of drug exposure causing exaggerated QT interval prolongation and torsades de pointes highlights the multicomponent nature of cardiac repolarization and the way in which simple perturbations can yield exaggerated responses. Future directions will involve cellular approaches coupled to evolving technologies that can interrogate multicellular systems and provide a sophisticated view of mechanisms in this previously idiosyncratic drug reaction. PMID- 27261831 TI - Atrial-Selective Potassium Channel Blockers. AB - Atrial fibrillation (AF) is associated with increased morbidity and mortality. Atrial-selective potassium (K(+)) channel blockers may represent a novel therapeutic target. The best validated atrial-specific ion currents are the acetylcholine-activated inward-rectifier K(+) current IK,ACh and ultrarapidly activating delayed-rectifier K(+) current IKur. Two-pore domain and small conductance Ca(2+)-activated K(+) channels and Kv1.1 channels may also contribute to the atrial repolarization. We review the molecular and electrophysiologic characteristics of atrial-selective K(+) channels and their potential pathophysiologic role in AF. We summarize currently available K(+) channel blockers focusing on the most important compounds. PMID- 27261832 TI - Dofetilide: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias. AB - Dofetilide is a class III antiarrhythmic agent with a selective blockade of rapid component of delayed rectifier potassium current (IKr). Dofetilide was found to be safe in patients after myocardial infarction and those with congestive heart failure and left ventricular systolic dysfunction (ejection fraction of less than 35%). An important adverse effect of dofetilide is its potential proarrhythmic risk of ventricular tachyarrhythmias, mostly torsades de pointes. Because dofetilide has about an 80% renal excretion, dose adjustment is required in patients with impaired renal function. Dofetilide should not be given or discontinued if the QTc is greater than 500 ms. PMID- 27261833 TI - Sotalol. AB - Sotalol is effective for treating atrial fibrillation (AF), ventricular tachycardia, premature ventricular contractions, and supraventricular tachycardia. Racemic (DL) sotalol inhibits the rapid component of the delayed rectifier potassium current. There is a near linear relationship between sotalol dosage and QT interval prolongation. However, in dose ranging trials in patients with AF, low-dose sotalol was not more effective than placebo. Orally administered sotalol has a bioavailability of nearly 100%. The only significant drug interactions are the need to avoid or limit use of concomitant drugs that cause QT prolongation, bradycardia, and/or hypotension. PMID- 27261834 TI - Dronedarone: Basic Pharmacology and Clinical Use. AB - Dronedarone is the newest antiarrhythmic drug approved for the maintenance of sinus rhythm in patients with nonpermanent atrial fibrillation (AF). It is a multi-channel blocker with diverse electrophysiologic properties. Dronedarone decreases the incidence of AF recurrence and the ventricular rate during recurrence. Dronedarone decreases rates of cardiovascular hospitalizations in patients with paroxysmal and persistent AF. Dronedarone increases mortality in patients with permanent AF and those with moderate-severe heart failure, and should thus be avoided in these populations. Dronedarone is less effective than amiodarone but also has less toxicity. Direct comparison with other antiarrhythmic drugs is not available. PMID- 27261835 TI - Ranolazine: Electrophysiologic Effect, Efficacy, and Safety in Patients with Cardiac Arrhythmias. AB - Ranolazine is currently approved as an antianginal agent in patients with chronic angina (class IIA). Ranolazine exhibits antiarrhythmic effects that are related to its multichannel blocking effect, predominantly inhibition of late sodium (late INa) current and the rapid potassium rectifier current (IKr), as well as ICa, late ICa, and INa-Ca. It also suppresses the early and delayed after depolarizations. Ranolazine is effective in the suppression of atrial and ventricular arrhythmias (off-label use) without significant proarrhythmic effect. Currently, ongoing trials are evaluating the efficacy and safety of ranolazine in patients with cardiac arrhythmias; preliminary results suggest that ranolazine, when used alone or in combination with dronedarone, is safe and effective in reducing atrial fibrillation. Ranolazine is not currently approved by the US Food and Drug Administration as an antiarrhythmic agent. PMID- 27261837 TI - Guidelines for Potassium Channel Blocker Use. AB - This article summarizes recommendations for the clinical use of antiarrhythmic drugs for the treatment and prevention of atrial and ventricular arrhythmias based on current guideline and consensus documents. The choice of antiarrhythmic drug is based on the efficacy and safety profile and influenced by the presence or absence of structural heart disease. Because of its adverse side-effect profile, amiodarone is recommended for the management of atrial fibrillation only when other agents have failed or are contraindicated. For treatment of symptomatic ventricular arrhythmias in the setting of structural heart disease, amiodarone is generally the preferred agent. PMID- 27261838 TI - The K(+) Channel: One Channel, Many Arrhythmias! PMID- 27261836 TI - Proarrhythmic and Torsadogenic Effects of Potassium Channel Blockers in Patients. AB - The most common arrhythmia requiring drug treatment is atrial fibrillation (AF), which affects 2 to 5 million Americans and continues to be a major cause of morbidity and increased mortality. Despite recent advances in catheter-based and surgical therapies, antiarrhythmic drugs continue to be the mainstay of therapy for most patients with symptomatic AF. However, many antiarrhythmics block the rapid component of the cardiac delayed rectifier potassium current (IKr) as a major mechanism of action, and marked QT prolongation and pause-dependent polymorphic ventricular tachycardia (torsades de pointes) are major class toxicities. PMID- 27261839 TI - Cardiac Potassium Channel Disorders: From Basics to Clinics. PMID- 27261840 TI - Gambling problems in treatment for affective disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). AB - BACKGROUND: Gambling problems co-occur frequently with other psychiatric difficulties and may complicate treatment for affective disorders. This study evaluated the prevalence and correlates of gambling problems in a U. S. representative sample reporting treatment for mood problems or anxiety. METHODS: n=3007 respondents indicating past-year treatment for affective disorders were derived from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Weighted prevalence estimates were produced and regression analyses examined correlates of gambling problems. RESULTS: Rates of lifetime and past year problem gambling (3+DSM-IV symptoms) were 3.1% (95% CI=2.4-4.0%) and 1.4% (95% CI=0.9-2.1%), respectively, in treatment for any disorder. Rates of lifetime problem gambling ranged from 3.1% (95% CI=2.3-4.3%) for depression to 5.4% (95% CI=3.2-9.0%) for social phobia. Past-year conditions ranged from 0.9% (95% CI=0.4 2.1%) in dysthymia to 2.4% (95% CI=1.1-5.3%) in social phobia. Higher levels were observed when considering a spectrum of severity (including 'at-risk' gambling), with 8.9% (95% CI=7.7-10.2%) of respondents indicating a history of any gambling problems (1+ DSM-IV symptoms). Lifetime gambling problems predicted interpersonal problems and financial difficulties, and marijuana use, but not alcohol use, mental or physical health, and healthcare utilisation. LIMITATIONS: Data were collected in 2001-02 and were cross-sectional. CONCLUSIONS: Gambling problems occur at non-trivial rates in treatment for affective disorders and have mainly psychosocial implications. The findings indicate scope for initiatives to identify and respond to gambling problems across a continuum of severity in treatment for affective disorders. PMID- 27261842 TI - Can oocyte quality be augmented? PMID- 27261841 TI - Breastfeeding and mental health in adulthood: A birth cohort study in Brazil. AB - BACKGROUND: Breastfeeding is negatively associate with behavioral and internalization problems, psychological stress, and depressive/anxiety symptoms. However, studies evaluating specific mental health disorders are scarce. We aimed to assess the association between breastfeeding and mental health outcomes in young adults. METHODS: In 1982, hospital deliveries in Pelotas (Southern Brazil) were identified; liveborns were examined and their mothers interviewed (n=5914). Information on breastfeeding was collected in early childhood. In 2012-13, at 30 years of age, we used the Mini International Neuropsychiatric Interview (MINI) for the diagnosis of major depression (MD), generalized anxiety disorder (GAD) and social anxiety disorder (SAD). In addition, we used the Beck Depression Inventory (BDI-II) and the Self-reported Questionnaire (SRQ-20), to evaluate depressive symptoms severity and common mental disorders (CMD), respectively. We used multivariable regression models to evaluate the association between breastfeeding and mental health outcomes. RESULTS: We evaluated 3657 individuals. Prevalence of CMD, MD, GAD and SAD was 24.3%, 7.9%, 12.7% and 3.6%, respectively. In multivariable models the odds of having a more severe case of depression (BDI II) was smaller among those breastfed for 6 or more months (OR=0.69 95%CI [0.53 0.89]). We observed a similar pattern for MD and CMD, however, confidence intervals included the reference. LIMITATIONS: We had no information on home environment characteristics during childhood. Lack of power and a small effect size could explain why we did not detect an association between breastfeeding and MD. CONCLUSION: Breastfeeding reduced the odds of having more severe depressive symptoms. PMID- 27261843 TI - Commentary on Classification of patients with incident non-specific low back pain: implications for research. AB - COMMENTARY ON: Norton G, McDonough CM, Cabral HJ, Shwartz M, Burgess JF Jr. Classification of patients with incident non-specific low back pain: implications for research. Spine J 2016;16:567-76 (in this issue). PMID- 27261844 TI - Consensus at last! Long-term results of all randomized controlled trials show that fusion is no better than non-operative care in improving pain and disability in chronic low back pain. AB - Commentary On: Hedlund R, Johansson C, Hagg O, Fritzell P, Tullberg T. Swedish Lumbar Spine Study Group. The long-term outcome of lumbar fusion in the Swedish lumbar spine study. Spine J 2016;16:579-87 (in this issue). PMID- 27261845 TI - Consensus building in metastatic spine disease. AB - COMMENTARY ON: Arana E, Kovacs FM, Royuela A, Asenjo B, Perez-Ramirez U, Zamora J, the Spanish Back Pain Research Network Task Force for the Improvement of Inter Disciplinary Management of Spinal Metastasis. Spine Instability Neoplastic Score: agreement across different medical and surgical specialties. Spine J 2016;16:591 9 (in this issue). PMID- 27261846 TI - Bringing truths from evidence: novel ways to detect pain derivation of low back. PMID- 27261847 TI - Gastric acid inhibitory and gastric protective effects of Cannabis and cannabinoids. AB - Cannabis sativa has long been known for its psychotropic effect. Only recently with the discovery of the cannabinoid receptors, their endogenous legends and the enzymes responsible for their synthesis and degradation, the role of this 'endocannabinoid system' in different pathophysiologic processes is beginning to be delineated. There is evidence that CB1 receptor stimulation with synthetic cannabinoids or Cannabis sativa extracts rich in Delta(9)-tetrahydrocannabinol inhibit gastric acid secretion in humans and experimental animals. This is specially seen when gastric acid secretion is stimulated by pentagastrin, carbachol or 2-deoxy-d-glucose. Cannabis and/or cannabinoids protect the gastric mucosa against noxious challenge with non-steroidal anti-inflammatory drugs, ethanol as well as against stress-induced mucosal damage. Cannabis/cannabinoids might protect the gastric mucosa by virtue of its antisecretory, antioxidant, anti-inflammatory, and vasodilator properties. PMID- 27261848 TI - Antioxidant and hepatoprotective effects of Ajuga nipponensis extract by ultrasonic-assisted extraction. AB - OBJECTIVE: To investigate suitable condition for extraction of the active components from Ajuga nipponensis (A. nipponensis). METHODS: Orthogonal experimental design was used to determine the optimal extraction parameters for ecdysterones and flavonoids. Finally, the hepatoprotective abilities of A. nipponensis extracts were evaluated by CCl4-induced animal models. RESULTS: Maximum yields of flavonoids (7.87 +/- 0.10) mg/g and ecdysterones (0.73 +/- 0.02) mg/g could be obtained when the extraction time was 50 min, the extraction temperature was 60 degrees C, and the ratio of sample to 70% (v/v) ethanol was 1:20 (w/w). The antioxidant property of A. nipponensis was correlated to the concentration of its extracts. At 5 mg/mL, A. nipponensis extract scavenged 84.8% of DPPH radical and had absorbance values of 2.43 +/- 0.04 reducing power. Upon CCl4-induced liver injury, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase decreased significantly after the mice were treated with A. nipponensis. Histological researches also explained that A. nipponensis reduced the extent of liver lesions induced by CCl4. CONCLUSIONS: A. nipponensis exhibited potent antioxidant activity in chemical experimental models and hepatoprotective effect against CCl4-induced liver damage. PMID- 27261849 TI - Anti-inflammatory activity of the essential oils of Cymbopogon validus (Stapf) Stapf ex Burtt Davy from Eastern Cape, South Africa. AB - OBJECTIVE: To evaluate the essential oil composition and the anti-inflammatory activity of Cymbopogon validus (C. validus) leaves and flowers. METHODS: A total of 300 g of fresh or dry (leaves and flowers) of C. validus were cut into small pieces and subjected to hydro-distillation method for approximately 5 h using the Clevenger apparatus. The extracted essential oils were then used for testing the anti-inflammatory activity. The anti-inflammatory activity was evaluated by using egg albumin-induced paw edema. RESULTS: The extracted oils had the following yields 2.2% for fresh leaves, 2.0% for dry leaves and 2.4% v/w for dry flowers. GC-MS results revealed that the oils contained artemisia ketone (37.5%), linalool (3.2%-29.6%), northujane (4.4%-16.8%), verbenone (13.5%), naphthalene (1.7% 9.6%), delta-cadinene (0.5%-8.1%), hedycaryol (5.4%-7.6%) and alpha-eudesmol (6.5%-6.7%) as the major constituents. C. validus essential oils showed significant (P < 0.05) anti-inflammatory effects from the first 30 min after albumin injection compared to aspirin which had a later onset of effect. CONCLUSIONS: The findings of this study show that the essential oil extracted from C. validus fresh or dry leaves and flowers have anti-inflammatory properties; that might be associated with the major components and the minor components found in the essential oils. PMID- 27261850 TI - Hydroethanolic extract of Smallanthus sonchifolius leaves improves hyperglycemia of streptozotocin induced neonatal diabetic rats. AB - OBJECTIVE: To evaluate the effect of hydroethanolic extract of yacon on the hyperglycemia induced by streptozotocin (STZ) in neonatal rats. METHODS: Wistar rats aged two days old received an intraperitoneal injection of STZ (160 mg/kg); after seven weeks, glycosuria was determined and animals with glucose levels above 250 mg/dL were included in the study. Groups of diabetic and non-diabetic rats were treated orally with yacon extract at a dose of 400 mg/kg/d for 14 d. Tests were made for phytochemical characterization, glucose tolerance and toxicity. RESULTS: The results showed that treatment with the extract reduced the glucose levels of fed diabetic rats and did not change the glucose levels of fasting diabetic and normal rats. Additionally, also it was observed that treatment with the extract reduced blood glucose levels of diabetic rats during the oral and intravenous glucose tolerance tests. There was no change in body weight, liver enzymes or mortality with yacon extract treatment. The phytochemical screening revealed the presence of caffeic acid, chlorogenic acid, ferulic acid and gallic acid. CONCLUSIONS: The data suggest that yacon extract reduces hyperglycemia, possibly by improving insulin sensibility through its phytochemicals constituents (phenolic compounds). PMID- 27261851 TI - Effects of feeding a diet containing Gymnema sylvestre extract: Attenuating progression of obesity in C57BL/6J mice. AB - OBJECTIVE: To investigate the effect of Gymnema sylvestre extract (GS) on initial anti-obesity, liver injury, and glucose homeostasis induced by a high-fat diet (HFD). METHODS: The dry powder of GS was extracted with methanol, and gymnemic acid was identified by high performance liquid chromatography as deacyl gymnemic acid. Male C57BL/6J mice that fed on either a normal diet, normal diet containing 1 g/kg GS (CON+GS), HFD, or HFD containing 1.0 g/kg GS (HFD + GS) for 4 weeks were used to test the initial anti-obesity effect of GS. Body weight gain and food intake, and serum levels about lipid and liver injury markers were measured. Histopathology of adipose tissue and liver stained with hematoxylin and eosin (H&E) and oil-red O were analyzed. After 4 weeks of GS extract feeding, intraperitoneal glucose tolerance test (IPGTT) was performed. RESULTS: The methanol extracts of GS exerted significant anti-obesity effects in HFD + GS group. They decreased body weight gain, a lower food and energy efficiency ratio, and showed lower serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL)-cholesterol, very-low density lipoprotein (VLDL) cholesterol and leptin compared with the HFD group. The decreases of abdominal as well as epididymal fat weight and adipocyte hypertrophy, lipid droplets in liver, and serum levels of aspartate aminotransferase (AST) and alanine transaminase (ALT) were also observed. The CON + GS group showed an effect of glucose homeostasis compared to the CON group. CONCLUSIONS: This study shows that GS provide the possibility as a key role in an initial anti-obesity effects feeding with a HFD. PMID- 27261852 TI - Zika Virus spreading in South America: Evolutionary analysis of emerging neutralizing resistant Phe279Ser strains. AB - OBJECTIVE: To investigate the genetic diversity of Zika Virus (ZIKV) and the relationships existing among these circulating viruses worldwide. To evaluate the genetic polymorphisms harbored from ZIKV that can have an influence on the virus circulation. METHODS: Three different ZIKV dataset were built. The first dataset included 63 E gene sequences, the second one 22 NS3 sequences and the third dataset was composed of 108 NS5 gene sequences. Phylogenetic and selective pressure analysis was performed. The edited nucleic acid alignment from the Envelope dataset was used to generate a conceptual translation to the corresponding peptide sequences through UGene software. RESULTS: The phylogeographic reconstruction was able to discriminate unambiguously that the Brazilian strains are belonged to the Asian lineage. The structural analysis reveals instead the presence of the Ser residue in the Brazilian sequences (however already observed in other previously reported ZIKV infections) that could suggest the presence of a neutralization-resistant population of viruses. CONCLUSIONS: Phylogenetic, evolutionary and selective pressure analysis contributed to improve the knowledge on the circulation of ZIKV. PMID- 27261853 TI - Evaluation of hypolipidemic Marrubium vulgare effect in Triton WR-1339-induced hyperlipidemia in mice. AB - OBJECTIVE: To evaluate the hypocholesterolemic and hypotriglyceridemic activities of four Marrbium vulgare herb extracts using Triton WR-1339-induced hyperlipidemia in mice. METHODS: Hyperlipidemia was developed by intraperitoneal injection of Triton (200 mg/kg body weight). The animals were divided into main four groups of eight mice each: normal control group, hyperlipidemic control group, hyperlipidemic plus tween-40 control and treated group. The fourth one was divided into four subgroups, petroleum ether extract group, chloroform extract group, ethyl acetate extract group and methanol extract treated group each of them contains two sub-sub group for treating animals with two doses at 0.1 and 0.25 LD50. RESULTS: After 7 h and 24 h of treatment, the intragastric administration of all extracts caused a significant decrease of plasma total cholesterol. Triglyceride levels were also significantly lowered by all extracts while petroleum ether produced the lowest decreasing level. Similar results were observed for LDL-cholesterol concentrations. Furthermore, more polar extracts (methanol and ethyl acetate)-soluble fractions showed a significant ameliorative action on elevated atherogenic index (AI) and LDL/HDL-C ratios, while these atherogenic markers were not statistically suppressed by the chloroform and petroleum ether-soluble extract. CONCLUSION: The findings indicated that Marrubium may contain polar products able to lower plasma lipid concentrations and might be beneficial in treatment of hyperlipidemia and atherosclerosis. PMID- 27261854 TI - Anti-Toxoplasma antibodies prevalence and associated risk factors among HIV patients. AB - OBJECTIVES: To assess the seroprevalence and associated risk factors of toxoplasmosis among HIV patients in Agaro Town Health Center of Jimma zone. METHODS: Convenient sampling was used to collect blood samples from 135 patients attending anti-retroviral therapy from February to March 2015. Serum samples were tested for anti-Toxoplasma gondii (T. gondii) antibody by using latex agglutination test. Structured questionnaire was used to collect data on socio demographic and risk factors associated with toxoplasmosis. RESULTS: Overall seroprevalence of toxoplasmosis was 80.7% (109/135, CI: 74.04-87.36). In multivariate analysis significant association was observed between anti-T. gondii seropositivity and raw meat consumption (OR: 3.514, CI: 1.167-10.581, P = 0.025), knowledge about toxoplasmosis (OR: 5.225, CI: 1.382, P = 0.015) and sex (OR: 4.023, CI: 1.382-19.762, P = 0.015). CONCLUSIONS: Immuno compromised patients showed high rate of seropositivity and thus, it is highly advisable to introduce routine anti-T. gondii antibodies serological screening test prior to ART commencement. PMID- 27261855 TI - Serological survey on some pathogens in wild brown hares (Lepus europaeus) in Central Italy. AB - OBJECTIVE: To determine the exposure of wild brown hares [Lepus europaeus (L. europaeus), pallas] to Anaplasma phagocytophilum (A. phagocytophilum), Borrelia burgdorferi (B. burgdorferi) sensu lato, Encephalitozoon cuniculi (E. cuniculi), Leishmania sp., Neospora caninum (N. caninum) and Toxoplasma gondii (T. gondii). METHODS: Two hundred twenty-two blood serum samples of wild brown hares captured in protected areas of the province of Pisa (Central Italy) were tested to detect antibodies against the reported pathogens. RESULTS: Thirty one (14.0%) animals resulted positive for at least one tested agent, with antibody titres ranging from 1:20 to 1:320. In particular, 13 (5.8%) samples were positive to B. burgdorferi s.l., 11 (4.9%) to N. caninum, 3 (1.3%) to T. gondii, 2 (0.9%) to A. phagocytophilum and 2 (0.9%) to Leishmania sp. No samples scored positive to E. cuniculi. Four animals (14.8%) resulted coinfected with 2 different pathogens. CONCLUSION: The obtained results showed that B. burgdorferi s.l. N. caninum, T. gondii, A. phagocytophilum and Leishmania sp. circulate in wild brown hares in Central Italy, suggesting a possible role of L. europaeus as reservoir of these pathogens. The obtained results showed that autochthonous wild brown hares living in Central Italy have been exposed to several pathogens circulating in this area, suggesting a possible role of L. europaeus as reservoir. PMID- 27261856 TI - Exploration of the regulatory effect of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. AB - OBJECTIVE: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. METHODS: Breast cancer cell lines MCF-7 were cultured and transfected with miR-21 mimics and the corresponding negative control mimics (NC mimics), and then MTS kits were used to detect cell viability. Transwell experiment was used to detect cell invasion ability, and fluorescence quantitative PCR was used to detect the expression of proliferation and invasion-related genes in cells. RESULTS: 24 h after transfection of miR-21 mimics and NC mimics, cell OD value and the number of invasive cells of miR-21 group were significantly higher than those of NC group, and mRNA contents of PDCD-4, FasL, PTEN, RhoB, Maspin, TIMP3 and RECK in cells were significantly lower than those of NC group. CONCLUSION: miR-21 can promote the proliferation and invasion of breast cancer cell lines, and its downstream target genes include PDCD-4, FasL, PTEN, RhoB, Maspin, TIMP3 and RECK. PMID- 27261857 TI - Mechanism of low molecular weight GTP binding protein RAC1 in injury of neural function of rats with cerebral ischemia reperfusion. AB - OBJECTIVE: To discuss the mechanism of low molecular weight GTP binding protein RAC1 in the injury of neural function based on building the rat model of cerebral ischemia reperfusion. METHODS: Middle cerebral artery of rats was ligated and the ligature was released to restore the perfusion after 2 h, the rat model of cerebral ischemia reperfusion injury was built, while the middle cerebral artery was ligated. The rats were randomly divided into the sham group, cerebral ischemia reperfusion group (I/R group) and the group with the injection of RAC1 activity inhibitor NSC23766 (NSC group). The survival and neurological severity score of rats in each group were observed and recorded. Nissl staining was employed to observe the nerve cells, and Western blot to detect expression of RAC1, superoxide dismutase and malondialdehyde. RESULTS: Number of nerve cells for rats in NSC group was significantly more than that in I/R group, but significantly less than that in sham group, with the statistical difference (P < 0.05). The brain water content for rats in NSC group was significantly lower than that in I/R group, but significantly higher than that in sham group, with the statistical difference (P < 0.05). The expression of RAC1 and malondialdehyde for rats in NSC group was significantly lower than that in I/R group, but higher than that in sham group; while the expression of superoxide dismutase was lower than that in sham group, but higher than that in I/R group, with the statistical difference (P < 0.05). CONCLUSIONS: The inhibition of RAC1 activity can reduce the oxidative stress, reduce the neurologic impairment because of cerebral ischemia reperfusion and thus protect the neural function. PMID- 27261858 TI - Involvement of alpha5 integrin in survivin-mediated osteosarcoma metastasis. AB - OBJECTIVE: To investigate the role of survivin in osteosarcoma metastasis. METHODS: Small interfering RNA (siRNA) was used to knockdown the expression of survivin and alpha5 integrin in the human osteosarcoma cell line MG63. Western blotting and immunostaining methods were used to assessed the effect of survivin knockdown on the expression of alpha5 integrin through flow cytometry and fluorescence microscopy detection. Meanwhile, the invasion and migration of transfected cells in Transwell and wound healing assays were probed, and the growth situation of these cells transplanted into nude mice was monitored. RESULTS: Knockdown of survivin expression could inhibit the invasion and migration of osteosarcoma MG64 cells in vitro and the expression of alpha5 integrin on osteosarcoma MG64 cell surface, suggesting that survivin can inhibit the invasion and migration of osteosarcoma cells through downregulation of alpha5 integrin. Anti-alpha5 integrin antibody could also markedly decrease the capability of invasion and migration of osteosarcoma MG64 cells. Additionally, knockdown of survivin expression could slow the growth of osteosarcoma MG63 cells transplanted into nude mice. CONCLUSIONS: Survivin-directed anti-tumor strategies might be an effective method in the treatment of osteosarcoma. PMID- 27261859 TI - Polarization of M1 tumor associated macrophage promoted by the activation of TLR3 signal pathway. AB - OBJECTIVE: To investigate the correlation between activation of toll-like receptors 3 (TLR3) signaling pathway and tumor-associated macrophage and its effect on the tumor growth. METHODS: The mice Lewis lung cancer cell lines 3LL and melanoma B16H10 were used to construct the subcutaneous transplantation tumor models and then they were treated with Poly-ICLC. The curative effect was observed and then the T cell and macrophage phenotypes infiltrated in local tumor were detected by flow cytometry. After the in vitro culture of mouse bone marrow derived macrophage, the real-time PCR and western blot were applied to detect the expression of macrophage activation markers and the activation of intracellular signaling pathways. RESULTS: The survival time of mice with brown tumor treated with Poly-ICLC significantly increased and the tumor growth was inhibited. The ratio of local tumor-infiltrated Treg decreased, while the ratio of CD8(+) T cell increased significantly. The macrophages surface CD206 expression was down regulated while the expression of iNOS increased. The Poly-ICLC could promote the expression of M1 markers (IL-1beta, TNF-alpha and iNOS) in bone marrow-derived macrophage and inhibited the expression of M2 molecules (Arg-1, YM-1 and CD206). The phosphorylation level of downstream p65, TBK1 and IRF3 increased significantly. CONCLUSIONS: The Poly-ICLC can activate the TLR3 downstream signaling pathway to induce a M1 polarization of tumor associated macrophage, thereby inhibiting the tumor growth. PMID- 27261860 TI - Influence of hydrogen sulfide on zymogen activation of homocysteine-induced matrix metalloproteinase-2 in H9C2 cardiocytes. AB - OBJECTIVE: To observe the influence of different concentrations of homocysteine (Hcy) and hydrogen sulfide (H2S) on the secretion and activation of matrix metalloproteinase-2 (MMP-2) in cardiocytes so as to search for new ways to fight against myocardial tissue fibrosis. METHODS: Cardiocytes H9C2 was cultured in vitro and different concentrations of Hcy and H2S were added for 6-h and 24-h cultivation. MTT cell proliferation assay was applied to test the activation change of cardiocytes H9C2 after affecting by different concentrations of Hcy and H2S. ELISA and MTT were employed to detect the expression and enzymatic activity of MMP-2. RESULTS: The H9C2 cell inhibition of activity was more significant with 1000 MUmol/L of Hcy as compared with other concentrations (P < 0.001). With 2.5 100.0 MUmol/L Hcy and 0.1, 1.0 and 10.0 mmol/L H2S, the activity of H9C2 did not change significantly (P > 0.05). Hcy with concentrations of 10, 50 and 100 MUmol/L could increase the quantity of MMP-2 secreted by cardiocytes H9C2, and the interaction strength was concentration-dependent (P < 0.05). After interacting with 100 MUmol/L of Hcy for 6 h, the zymogen activation effect of MMP 2 was stronger than that of the 2.5-25 MUmol/L group (P < 0.05). After interacting with Hcy and H2S (1.0 mmol/L) for 6 h and 24 h, the activation effect of MMP-2 was stronger than those interacted with 10, 25, 50 and 100 MUmol/L of Hcy (P < 0.05). CONCLUSIONS: Hcy can increase the production of MMP-2 secreted by H9C2 cell and improve its zymogen activation. Besides, the interaction strength is concentration-dependent; while H2S can up-regulate the activation of MMP-2 and co-promote the activation of MMP-2 with Hcy as well. PMID- 27261861 TI - Effect and mechanism of miR-34a on proliferation, apoptosis and invasion of laryngeal carcinoma cells. AB - OBJECTIVE: To discuss the effect and mechanism of miR-34a on the proliferation, apoptosis and invasion of laryngeal carcinoma cells. METHODS: The laryngeal squamous carcinoma Hep2 cells were transiently transfected with miR-34a mimics and miR-34a NC. The MTT, colony-forming assay, Hoechst staining and AnnexinV-PI double staining flow cytometry were employed to detect the effect of miR-34a on the viability and apoptosis of laryngeal squamous carcinoma Hep2 cells; Transwell assay to defect the effect of miR-34a on the migration and invasion of laryngeal squamous carcinoma Hep2 cells; western blot and RT-PCR assay to defect the effect of miR-34a mimics on the expression of survivin and Ki-67 mRNA in laryngeal squamous carcinoma Hep2 cells. RESULTS: Compared with miR-34a NC group, the cell viability in miR-34 mimics group was significantly decreased (P < 0.01), the cell apoptosis rate was significantly increased (P < 0.01), the abilities of cell migration and invasion were significantly reduced (P < 0.01) and the expression of survivin and Ki-67 mRNA was significantly decreased (P < 0.01). CONCLUSIONS: The increased expression of miR-34a can induce the apoptosis of Hep2 laryngeal carcinoma cells and inhibit the cell proliferation and invasion, which is related to the down-regulated expression of survivin and Ki-67. PMID- 27261862 TI - Study on the role of Cathepsin B and JNK signaling pathway in the development of cerebral aneurysm. AB - OBJECTIVE: To investigate the correlation between JNK signal and the apoptosis of VSMC as well as the expression of Cathepsin B and to explore the role of JNK signal in the development of cerebral aneurysm. METHODS: Rat models of cerebral aneurysm were established and histopathologic changes of cerebral aneurysm and the apoptosis of VSMC were analyzed. Rat models were respectively subject to subcutaneous injection of Cathepsin B siRNA and JNK inhibitor SP600125. Western blot technique was used to detect the expression of proteins like Cathepsin B, Caspase-3, and p-JNK. Spearman's rho was used to examine the correlation between p-JNK and Cathepsin B, as well as the expression of relevant proteins. RESULTS: The success rate of modeling rats with cerebral aneurysm was 88.75%. After the respective injection of Cathepsin B siRNA, SP600125 and their combination, the cell densities of VSMC of rats with cerebral aneurysm all increased significantly (P < 0.05 or P < 0.01), but the apoptosis rate of VSMC decreased significantly (P < 0.01). Compared with normal rats, the expression of Cathepsin B, Caspase-3 and p-JNK in Cerebral aneurysm models increased significantly. Effectively intervening Cathepsin B genes with Cathepsin B siRNA could significantly inhibit the expression of Cathepsin B and Caspase-3, but hardly influence the expression of p-JNK. JNK inhibitor SP600125 had no influence on the expression of Cathepsin B and Caspase-3, but effectively inhibited the expression of p-JNK. In cerebral aneurysm tissues, positive correlation was observed between the expression of p JNK and Cathepsin B, the correlation coefficient was r = 0.640. CONCLUSION: After the attack of cerebral aneurysm, proteins like Cathepsin B, Caspase-3 and p-JNK are all involved in the apoptosis of VSMCs. This process may be realized by Cathepsin B which activates the apoptosis mechanism of Caspase-3 and mediate the apoptosis of VSMC through the JNK signaling pathway. Therefore, silencing Cathepsin B gene or inhibiting the conduction through JNK signaling pathway can mitigate the apoptosis of vascular smooth muscle cells in cerebral aneurysm. PMID- 27261863 TI - Mechanism of TLR-4/NF-kappaB pathway in myocardial ischemia reperfusion injury of mouse. AB - OBJECTIVE: To detect the expression of Toll-like receptor 4 (TLR-4) and NF-kappaB and to discuss the mechanism of TLR-4/NF-kappaB pathway in the myocardial ischemia reperfusion injury of mouse. METHODS: TLR-4 mutant mice and wild homozygous mice were divided into the model group and sham group. Mice in the model group were given the ligation of left anterior descending coronary artery for the modeling, while mice in the sham group were not given the ligation after threading. The cardiac muscle tissues were collected for the morphological observation. The immunohistochemistry was employed to detect the expression of NF kappaB, Western blot was used to detect the expression of TLR-4 and ELISA to detect the expression of serum inflammatory factors. RESULTS: The expression of NF-kappaB in TLR-4 null mice after the myocardial ischemia reperfusion was significantly lower than that in wild homozygous mice. For the model group and sham group, the expression of TLR-4 in wild homozygous mice was all significantly higher than that in TLR-4 null mice, while the expression of TLR-4 in TLR-4 null mice in the model group was significantly higher than that in sham group, with the statistical difference (P < 0.05). The expression of inflammatory factors in TLR-4 null mice and wild homozygous mice in the model group was significantly higher than that in sham group. The expression of all factors in group A with TLR 4 null was significantly lower than that in group B with wild homozygous type, with the statistical difference (P < 0.05). CONCLUSIONS: TLR-4/NF-kappaB pathway is closely related to the myocardial ischemia reperfusion injury, which plays its role through the release of inflammatory cytokines. PMID- 27261864 TI - Inhibition of long non-coding RNA TUG1 on gastric cancer cell transference and invasion through regulating and controlling the expression of miR-144/c-Met axis. AB - OBJECTIVE: To discuss the expression of long noncoding RNA TUG1 (lncRNA-TUG1) in gastric carcinoma (GC) and its effects on the transferring and invading capacity of gastric carcinoma cells. METHODS: Forty cases of carcinoma tissue and para carcinoma tissue were selected from GC patients who underwent surgical removal in Zhejiang Provincial Hospital of Chinese Traditional Medicine and Wenzhou Central Hospital from January, 2013 to December, 2014; the expressing level of lncRNA TUG1 in GC and para-C tissues was detected by applying the qRT-PCR technique. The correlation between lncRNA-TUG1 expression and patients' clinical data was classified and analyzed. SGC-7901 cells were transfected using lncRNA-TUG1 specific siRNA. Changes of the transferring and invading capacity of siRNA transfected SGC-7901 cells were scratch-tested and transwell-detected. qRT-PCR was applied to detect the expression level of microRNA-144 after lncRNA-TUG1 was silenced. Changes of c-Met mRNA and protein expressions was detected by qRT-PCR and western-blot test. RESULTS: The expression level of lncRNA-TUG1 in GC tissue was significant higher than that in para-C tissue (P < 0.05) and the high expression level of lncRNA-TUG1 in GC tissue was significantly correlated with tumor lymph nodes metastasis and advance TNM phasing (P < 0.05). The transferring and invading capacity of SGC-7901 cells was highly inhibited after being transfected by lncRNA-TUG1 specific siRNA (P < 0.05). The results of qRT-PCR and western-blot proved that the expression of microRNA-144 was significantly boosted and the expression level of c-Met mRNA and protein was inhibited after lncRNA TUG1 was silenced (P < 0.05). CONCLUSIONS: lncRNA-TUG1 shows an up-regulated expression in GC tissue and that bears a correlation with clinicopathological features of malignant tumor. lncRNA-TUG1 can promote the transferring and invading capacity of GC by inhibiting the pathway of microRNA-144/c-Met. PMID- 27261865 TI - Afebrile, asymptomatic and non-thrombocytopenic Zika virus infection: Don't miss it! PMID- 27261866 TI - The UK Cancer Drugs Fund Experiment and the US Cancer Drug Cost Problem: Bearing the Cost of Cancer Drugs Until It Is Unbearable. PMID- 27261868 TI - Emergency Contraception. AB - Emergency contraception (EC) may help prevent pregnancy in various circumstances, such as contraceptive method failure, unprotected sexual intercourse, or sexual assault, yet it remains underused. There are 4 approved EC options in the United States. Although ulipristal acetate requires a provider's prescription, oral levonorgestrel (LNG) is available over the counter for women of all ages. The most effective method of EC is the copper intrauterine device, which can be left in place for up to 10 years for efficacious, cost-effective, hormone-free, and convenient long-term primary contraception. Ulipristal acetate tends to be more efficacious in pregnancy prevention than is LNG, especially when taken later than 72 hours postcoitus. The mechanism of action of oral EC is delay of ovulation, and current evidence reveals that it is ineffective postovulation. Women who weigh more than 75 kg or have a body mass index greater than 25 kg/m(2) may have a higher risk of unintended pregnancy when using oral LNG EC; therefore, ulipristal acetate or copper intrauterine devices are preferable in this setting. Providers are often unaware of the range of EC options or are unsure of how to counsel patients regarding the access and use of EC. This article critically reviews current EC literature, summarizes recommendations, and provides guidance for counseling women about EC. Useful tips for health care providers are provided, with a focus on special populations, including breast-feeding women and those transitioning to long-term contraception after EC use. When treating women of reproductive age, clinicians should be prepared to counsel them about EC options, provide EC appropriately, and, if needed, refer for EC in a timely manner. PMID- 27261869 TI - Association of Objectively Measured Physical Activity With Objectively Measured Visual Acuity Among a Population-Based Sample of Patients With Coronary Artery Disease and Congestive Heart Failure: the Cardio-ocular Paradigm. PMID- 27261867 TI - My Approach to the Patient With Familial Hypercholesterolemia. AB - Familial hypercholesterolemia (FH), a relatively common Mendelian genetic disorder, is associated with a dramatically increased lifetime risk of premature atherosclerotic cardiovascular disease due to elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. The diagnosis of FH is based on clinical presentation or genetic testing. Early identification of patients with FH is of great public health importance because preventive strategies can lower the absolute lifetime cardiovascular risk and screening can detect affected relatives. However, low awareness, detection, and control of FH pose hurdles in the prevention of FH-related cardiovascular events. Of the estimated 0.65 million to 1 million patients with FH in the United States, less than 10% carry a diagnosis of FH. Based on registry data, a substantial proportion of patients with FH are receiving no or inadequate lipid-lowering therapy. Statins remain the mainstay of treatment for patients with FH. Lipoprotein apheresis and newly approved lipid-lowering drugs are valuable adjuncts to statin therapy, particularly when the LDL-C-lowering response is suboptimal. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 provide an additional approximately 60% lowering of LDL-C levels and are approved for use in patients with FH. For homozygous FH, 2 new drugs that work independent of the LDL receptor pathway are available: an apolipoprotein B antisense oligonucleotide (mipomersen) and a microsomal triglyceride transfer protein inhibitor (lomitapide). This review attempts to critically examine the available data to provide a summary of the current evidence for managing patients with FH, including screening, diagnosis, treatment, and surveillance. PMID- 27261870 TI - Body Fat Percentage Should Not Be Confused With Lifestyle Behaviors. PMID- 27261871 TI - In Reply-Body Fat Percentage Should Not Be Confused With Lifestyle Behaviors. PMID- 27261872 TI - Epidemiology of Sarcoidosis. PMID- 27261873 TI - In Reply-Epidemiology of Sarcoidosis. PMID- 27261874 TI - Correction. PMID- 27261875 TI - Fanconi Anemia-Protean Manifestations of Defective DNA Repair. PMID- 27261876 TI - An Adult Male With Hypophosphatemic Osteomalacia. PMID- 27261877 TI - VR-28 Nova Fahrenheit by Jimmy Descant. AB - Recognizing the contribution art has had in the Mayo Clinic environment since the original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings features some of the numerous works of art displayed throughout the buildings and grounds on Mayo Clinic campuses as interpreted by the author. PMID- 27261878 TI - Prefrontal activity during working memory is modulated by the interaction of variation in CB1 and COX2 coding genes and correlates with frequency of cannabis use. AB - The CB1 cannabinoid receptor is targeted in the brain by endocannabinoids under physiological conditions as well as by delta9-tetrahydrocannabinol under cannabis use. Furthermore, its signaling appears to affect brain cognitive processing. Recent findings highlight a crucial role of cyclooxygenase-2 (COX-2) in the mechanism of intraneuronal CB1 signaling transduction, while others indicate that two single nucleotide polymorphisms (SNPs) (rs1406977 and rs20417) modulate expression of CB1 (CNR1) and COX-2 (PTGS2) coding genes, respectively. Here, our aim was to use fMRI to investigate in healthy humans whether these SNPs interact in modulating prefrontal activity during working memory processing and if this modulation is linked with cannabis use. We recruited 242 healthy subjects genotyped for CNR1 rs1406977 and PTGS2 rs20417 that performed the N-back working memory task during fMRI and were interviewed using the Cannabis Experience Questionnaire (CEQ). We found that the interaction between CNR1 rs1406977 and PTGS2 rs20417 is associated with dorsolateral prefrontal cortex (DLPFC) activity such that specific genotype configurations (CNR1 C carriers/PTGS2 C carriers and CNR1 TT/PTGS2 GG) predict lower cortical response versus others in spite of similar behavioral accuracy. Furthermore, DLPFC activity in the cluster associated with the CNR1 by PTGS2 interaction was negatively correlated with behavioral efficiency and positively correlated with frequency of cannabis use in cannabis users. These results suggest that a genetically modulated balancing of signaling within the CB1-COX-2 pathway may reflect on more or less efficient patterns of prefrontal activity during working memory. Frequency of cannabis use may be a factor for further modulation of CNR1/PTGS2-mediated cortical processing associated with this cognitive process. PMID- 27261879 TI - Genotoxic effects induced by the exposure to an environmental mixture of illicit drugs to the zebra mussel. AB - Despite the growing interest on the presence of illicit drugs in freshwater ecosystems, just recently the attention has been focused on their potential toxicity towards non-target aquatic species. However, these studies largely neglected the effects induced by exposure to complex mixtures of illicit drugs, which could be different compared to those caused by single psychoactive molecules. This study was aimed at investigating the genetic damage induced by a 14-day exposure to a realistic mixture of the most common illicit drugs found in surface waters worldwide (cocaine, benzoylecgonine, amphetamine, morphine and 3,4 methylenedioxymethamphetamine) on the zebra mussel (Dreissena polymorpha). The mixture caused a significant increase of DNA fragmentation and triggered the apoptotic process and micronuclei formation in zebra mussel hemocytes, pointing out its potential genotoxicity towards this bivalve species. PMID- 27261880 TI - Effects of erythromycin, trimethoprim and clindamycin on attached microbial communities from an effluent dominated prairie stream. AB - In this study, differing metrics were utilized to measure effects of erythromycin (ER), trimethoprim (TR) and clindamycin (CL) on the structure and function of attached Wascana Creek, SK microbial communities. All three test antibiotics, especially ER, affected community structure and function of biofilms grown in rotating annular reactors. Biofilm thickness, bacterial biomass, and lectin binding biovolume (exopolymeric substances) were consistently less in ER treated biofilms when compared to the control. As well negative effects on protozoan numbers, and carbon utilization were detected. Finally, PCA analyses of DGGE results indicated that bacterial community diversity in ER exposed biofilms was always different from the control. ER exhibited toxic effects even at lower concentrations. Observations on TR and CL exposed biofilms indicated that bacterial biomass, lectin binding biovolume and carbon utilization were negatively affected as well. In terms of bacterial community diversity, however, CL exposed biofilms tended to group with the control while TR grouped with nutrient additions suggesting both nutritive and toxic effects. This study results represent an important step in understanding antibiotic effects, especially ER, on aquatic microbial communities. And because ER is so ubiquitous in receiving water bodies worldwide, the Wascana study results suggest the possibility of ecosystem disturbance elsewhere. CAPSULE ABSTRACT: Erythromycin (ER) is ubiquitous in waterbodies receiving sewage effluent. Structure and function of microbial communities from an effluent dominated stream were negatively affected by ER, at realistic concentrations. PMID- 27261881 TI - Transcriptional response of four C1q domain containing protein (C1qDC) genes from Venerupis philippinarum exposed to the water soluble fraction of No.0 diesel oil. AB - As pattern recognitionreceptors, the C1q-domain-containing (C1qDC) proteins play an important role in the pathogen recognition and complement pathway activation. In the present study, four novel C1q domain containing proteins (designated as VpC1qDC1, VpC1qDC2, VpC1qDC3 and VpC1qDC4) were cloned and characterized from clam Venerupis philippinarum. The four VpC1qDCs all possessed the conserved features critical for the fundamental structure and function of the C1q family. The four VpC1qDCs genes showed differential response profiles after exposure to the water soluble fraction of No.0 diesel oil (WSFD). More notably, VpC1qDC1 and VpC1qDC3 were more sensitive to low concentration of WSFD, as their mRNA level changed by higher magnitudes. In addition, VpC1qDC2 and VpC1qDC4 displayed notable increases with larger amplitude to high concentration of WSFD. All these results suggested that the transcriptional response of VpC1qDCs genes were probably a protective mechanism of the cell to oils pollution. The diverse expression patterns of VpC1qDCs demonstrated that VpC1qDC1 and VpC1qDC3 were sensitive responders to environmental stress in V. philippinarum. PMID- 27261882 TI - Allotype specific interactions of drugs and HLA molecules in hypersensitivity reactions. AB - It is hypothesised that associations between adverse drug reactions and specific alleles of the human leukocyte antigens arise due to specific interactions between the human leukocyte antigen molecules and the causative drug that stimulate immune responses targeting drug exposed tissues. To date this has only been definitively demonstrated for abacavir, an antiretroviral that causes a systemic adverse drug reaction, abacavir hypersensitivity syndrome, solely in HLA B*57:01+ individuals. Whilst this has informed the modification of abacavir to remove immunogenicity, there remains an imperative to define other interactions between drugs and specific HLA in order to understand the scope of interactions that can drive T cell mediated drug hypersensitivity. Here we review the current state of understanding of these interactions. PMID- 27261883 TI - Measurements of major VOCs released into the closed cabin environment of different automobiles under various engine and ventilation scenarios. AB - Volatile organic compounds (VOCs) in automobile cabins were measured quantitatively to describe their emission characteristics in relation to various idling scenarios using three used automobiles (compact, intermediate sedan, and large sedan) under three different idling conditions ([1] cold engine off and ventilation off, [2] exterior air ventilation with idling warm engine, and [3] internal air recirculation with idling warm engine). The ambient air outside the vehicle was also analyzed as a reference. A total of 24 VOCs (with six functional groups) were selected as target compounds. Accordingly, the concentration of 24 VOC quantified as key target compounds averaged 4.58 +/- 3.62 ppb (range: 0.05 (isobutyl alcohol) ~ 38.2 ppb (formaldehyde)). Moreover, if their concentrations are compared between different automobile operational modes: the 'idling engine' levels (5.24 +/- 4.07) was 1.3-5 times higher than the 'engine off' levels (4.09 +/- 3.23) across all 3 automobile classes. In summary, automobile in-cabin VOC emissions are highly contingent on changes in engine and ventilation modes. PMID- 27261884 TI - Changes in leaf area, nitrogen content and canopy photosynthesis in soybean exposed to an ozone concentration gradient. AB - Influences of ozone (O3) on light-saturated rates of photosynthesis in crop leaves have been well documented. To increase our understanding of O3 effects on individual- or stand level productivity, a mechanistic understanding of factors determining canopy photosynthesis is necessary. We used a canopy model to scale photosynthesis from leaf to canopy, and analyzed the importance of canopy structural and leaf ecophysiological characteristics in determining canopy photosynthesis in soybean stands exposed to 9 concentrations of [O3] (37-116 ppb; 9-h mean). Light intensity and N content peaked in upper canopy layers, and sharply decreased through the lower canopy. Plant leaf area decreased with increasing [O3] allowing for greater light intensity to reach lower canopy levels. At the leaf level, light-saturated photosynthesis decreased and dark respiration increased with increasing [O3]. These data were used to calculate daily net canopy photosynthesis (Pc). Pc decreased with increasing [O3] with an average decrease of 10% for an increase in [O3] of 10 ppb, and which was similar to changes in above-ground dry mass production of the stands. Absolute daily net photosynthesis of lower layers was very low and thus the decrease in photosynthesis in the lower canopy caused by elevated [O3] had only minor significance for total canopy photosynthesis. Sensitivity analyses revealed that the decrease in Pc was associated with changes in leaf ecophysiology but not with decrease in leaf area. The soybean stands were very crowded, the leaves were highly mutually shaded, and sufficient light for positive carbon balance did not penetrate to lower canopy leaves, even under elevated [O3]. PMID- 27261885 TI - Electrochemical immunosensor constructed using TiO2 nanotubes as immobilization scaffold and tracing tag. AB - A ternary TiO2 nanotube (TNT) composite and a signal antibody and horseradish peroxidase (HRP) functionalized TNT were designed as an electrode scaffold for immobilization of high quantity of capture antibody and a tracing tag for immunosensing, respectively. The polyaniline (PANI) was coated on TNTs by chemical oxidative polymerization, and gold nanoparticles were deposited on TNT PANI with a routine chemical reduction. Various techniques including scanning electron microscopy, energy dispersive X-ray, transmission electron microscope, X ray diffraction, Fourier transform infrared spectra, X-ray photoelectron spectra, impedance and electrochemical techniques were used to characterize the nano materials. Using bis(sulfosuccinimidyl) suberate as amino cross-linker, the TNT composite could be further functionalized with protein G' for oriented immobilization of capture antibody on electrode surface. Upon sandwich-type immunoreaction, the signal antibody on the tracing tag was quantitatively captured on the surface to generate sensitive electrochemical response with a H2O2 mediated HRP catalytic reaction. With alpha-fetoprotein as an analyte model, the immunosensor showed a linear range of 0.01-350ngmL(-1) with a detection limit of 1.5pgmL(-1). The accelerated electron transfer by the ternary composite, oriented immobilization of capture antibody and high loading of HRP on the TNT tracing tag greatly amplified the electrochemical signal, and led to the superior performance of the immunoassay. PMID- 27261886 TI - Novel surface antigen based impedimetric immunosensor for detection of Salmonella typhimurium in water and juice samples. AB - A specific surface antigen, OmpD has been reported first time as a surface biomarker in the development of selective and sensitive immunosensor for detecting Salmonella typhimurium species. The OmpD surface antigen extraction was done from Salmonella typhimurium serovars, under the optimized growth conditions for its expression. Anti-OmpD antibodies were generated and used as detector probe in immunoassay format on graphene-graphene oxide (G-GO) modified screen printed carbon electrodes. The water samples were spiked with standard Salmonella typhimurium cells, and detection was done by measuring the change in impedimetric response of developed immunosensor to know the concentration of serovar Salmonella typhimurium. The developed immunosensor was able to specifically detect S. typhimurium in spiked water and juice samples with a sensitivity upto 10(1)CFUmL(-1), with high selectivity and very low cross-reactivity with other strains. This is the first report on the detection of Salmonella typhimurum species using a specific biomarker, OmpD. The developed technique could be very useful for the detection of nontyphoidal Salmonellosis and is also important from an epidemiological point of view. PMID- 27261887 TI - Highly engineered biocatalysts for efficient small molecule pharmaceutical synthesis. AB - Technologies for the engineering of biocatalysts for efficient synthesis of pharmaceutical targets have advanced dramatically over the last few years. Integration of computational methods for structural modeling, combined with high through put methods for expression and screening of biocatalysts and algorithms for mining experimental data, have allowed the creation of highly engineered biocatalysts for the efficient synthesis of pharmaceuticals. Methods for the synthesis of chiral alcohols and amines have been particularly successful, along with the creation of non-natural activities for such desirable reactions as cyclopropanation and esterification. PMID- 27261888 TI - Salt or cocrystal of salt? Probing the nature of multicomponent crystal forms with infrared spectroscopy. PMID- 27261889 TI - An investigation of the effect of silicone oil on polymer intraocular lenses by means of PALS, FT-IR and Raman spectroscopies. AB - The effect of the polydimethylsiloxane (PDMS) based silicone oil, that is widely used in vitreoretinal surgery, on internal structures of the polymer intraocular lenses was investigated. The effect of PDMS was studied on the polymethyl methacrylate (PMMA) rigid lenses and poly(2-hydroxyethyl methacrylate) (PHEMA) flexible lenses. The research was carried out by means of the positron lifetime spectroscopy (PALS) as well as the infrared spectroscopy (FT-IR) and the Raman spectroscopy (RS). The studies involving the use of PALS and FT-IR methods have revealed that the PHEMA based lenses absorbed, whereas the PMMA lenses did not absorb, silicone oil. The results obtained with the use of the RS method were inconclusive, probably due to the too low intensity of the characteristic PDMS bands. The evidence from this study was discussed in terms of physics and related to the clinical use of both silicone oil and intraocular lenses. PMID- 27261890 TI - A highly selective colorimetric and "turn-on" fluorimetric chemosensor for detecting CN(-) based on unsymmetrical azine derivatives in aqueous media. AB - A novel highly selective chemosensor S1 for cyanide based on unsymmetrical azine derivative was successfully designed and synthesized, which showed both colorimetric and fluorescence turn-on responses for cyanide ions in aqueous. This structurally simple chemosensor could detect CN(-) anion over other anions in aqueous solution DMSO/H2O (v/v=3:2) undergo deprotonation reaction. Results showed that the chemosensor S1 exhibited 50 fold enhancement in fluorescence at 530nm and showed an obvious change in color from colorless to yellow that could be detected by naked eye under the UV-lamp after the addition of CN(-) in aqueous solution. Moreover, the detection limit on fluorescence response of the sensor to CN(-) is down to 6.17*10(-8)M by titration method. Test strips based on S1 were obtain, which could be used as a convenient and efficient CN(-) test kit to detect CN(-) in aqueous solution. PMID- 27261891 TI - Sin Nombre hantavirus nucleocapsid protein exhibits a metal-dependent DNA specific endonucleolytic activity. AB - We demonstrate that the nucleocapsid protein of Sin Nombre hantavirus (SNV-N) has a DNA-specific endonuclease activity. Upon incubation of SNV-N with DNA in the presence of magnesium or manganese, we observed DNA digestion in sequence unspecific manner. In contrast, RNA was not affected under the same conditions. Moreover, pre-treatment of SNV-N with RNase before DNA cleavage increased the endonucleolytic activity. Structure-based protein fold prediction using known structures from the PDB database revealed that Asp residues in positions 88 and 103 of SNV-N show sequence similarity with the active site of the restriction endonuclease HindIII. Crystal structure of HindIII predicts that residues Asp93 and Asp108 are essential for coordination of the metal ions required for HindIII DNA cleavage. Therefore, we hypothesized that homologous residues in SNV-N, Asp88 and Asp103, may have a similar function. Replacing Asp88 and Asp103 by alanine led to an SNV-N protein almost completely abrogated for endonuclease activity. PMID- 27261892 TI - A novel cell-based assay to measure activity of Venezuelan equine encephalitis virus nsP2 protease. AB - The encephalitic alphaviruses encode nsP2 protease (nsP2pro), which because of its vital role in virus replication, represents an attractive target for therapeutic intervention. To facilitate the discovery of nsP2 inhibitors we have developed a novel assay for quantitative measurement of nsP2pro activity in a cell-based format. The assay is based on a substrate fusion protein consisting of eGFP and Gaussia luciferase (Gluc) linked together by a small peptide containing a VEEV nsp2pro cleavage sequence. The expression of the substrate protein in cells along with recombinant nsP2pro results in cleavage of the substrate protein resulting in extracellular release of free Gluc. The Gluc activity in supernatants corresponds to intracellular nsP2pro-mediated substrate cleavage; thus, providing a simple and convenient way to quantify nsP2pro activity. Here, we demonstrate potential utility of the assay in identification of nsP2pro inhibitors, as well as in investigations related to molecular characterization of nsP2pro. PMID- 27261893 TI - Irritable Bowel Syndrome and Female Patients. AB - Irritable bowel syndrome is probably the most common functional gastrointestinal disorder and is characterized by abdominal pain along with altered bowel function. It is a disorder of female predominance. This article focuses on how being female influences the pathophysiology, diagnosis, management, and treatment of this common disorder and discusses the evidence and important controversies related to these areas. PMID- 27261894 TI - Chronic Constipation. AB - Chronic constipation is a common disorder that affects approximately 20% of the population and significantly impacts an individual's quality of life. The diagnosis can be made using standard criteria, and in the absence of alarm signs or symptoms, a determination of the underlying etiology/etiologies should be undertaken. In many instances, these will be gleaned from the history and physical examination. Specialized diagnostic testing may be warranted after the failure of initial laxative trials. Many therapeutic classes of laxatives exist with recent analyses indicating that practicing physicians prefer to use over-the counter therapies in lieu of more strongly evidence-based prescription pharmaceuticals. PMID- 27261895 TI - Fecal Incontinence and Pelvic Floor Dysfunction in Women: A Review. AB - Pelvic floor dysfunction and fecal incontinence is a common and debilitating condition in women, particularly as women age, and often goes under-reported to health care providers. It is important for providers to ask patients about possible symptoms. An algorithm for evaluation and treatment is presented. Current and future therapies are described and discussed. PMID- 27261896 TI - Upper Gastrointestinal Tract Motility Disorders in Women, Gastroparesis, and Gastroesophageal Reflux Disease. AB - This article reviews the sex differences in upper gastrointestinal (GI) motility for both healthy and common dysmotility conditions. It focuses on gastroesophageal reflux disease and other esophageal motor disorders for the esophagus and on gastroparesis and accelerated gastric emptying for the stomach. It also describes differences in upper GI motility signs and symptoms during each female hormonal stage (ie, menstrual cycle, pregnancy, perimenopause, menopause) for both healthy participants and those suffering from one of the aforementioned upper GI dysmotility conditions. More research still needs to be conducted to better understand sex differences in upper GI motility. PMID- 27261897 TI - Complex Relationships Between Food, Diet, and the Microbiome. AB - Diet is a risk factor in several medically important disease states, including obesity, celiac disease, and functional gastrointestinal disorders. Modification of diet can prevent, treat, or alleviate some of the symptoms associated with these diseases and improve general health. It is important to provide patients with simple dietary recommendations to increase the probability of successful implementation. These recommendations include increasing vegetable, fruit, and fiber intake, consuming lean protein sources to enhance satiety, avoiding or severely limiting highly processed foods, and reducing portion sizes for overweight and obese patients. PMID- 27261898 TI - Gastrointestinal Diseases in Pregnancy: Nausea, Vomiting, Hyperemesis Gravidarum, Gastroesophageal Reflux Disease, Constipation, and Diarrhea. AB - Many disorders of the gastrointestinal tract are common in pregnancy. Elevated levels of progesterone may lead to alterations in gastrointestinal motility which could contribute to nausea, vomiting, and/or GERD. Pregnancy-induced diarrhea may be due to elevated levels prostaglandins. This article reviews the normal physiologic and structural changes associated with pregnancy that could contribute to many of the common gastrointestinal complaints in pregnant patients. Additionally, the appropriate clinical and laboratory evaluations, other pathologic conditions that should be included in the differential, as well as the nonpharmacologic and pharmacologic therapies for each of these conditions is discussed. PMID- 27261899 TI - Pregnancy and the Patient with Inflammatory Bowel Disease: Fertility, Treatment, Delivery, and Complications. AB - For many women with inflammatory bowel disease (IBD), the illness coincides with their childbearing years. IBD increases the risk of pregnancy complications and adverse pregnancy outcomes. The multidisciplinary care team should emphasize the importance of medication adherence to achieve preconception disease control and maintain corticosteroid-free remission throughout pregnancy. Medication adjustments to reduce fetal exposure may be considered on an individualized basis in quiescent disease; however, any benefits of such adjustments remain theoretic and there is risk of worsening disease activity. Mode of delivery is determined by obstetric indications, except for women with active perianal disease who should consider cesarean delivery. PMID- 27261900 TI - Caring for Women with Inflammatory Bowel Disease. AB - Ulcerative colitis and Crohn disease are chronic inflammatory diseases with typical onset in early adulthood. These diseases, therefore, can affect a woman throughout the many stages of her life, including menstruation, sexuality, pregnancy, and menopause. Unique health issues face women during these stages and can affect the course of their inflammatory bowel disease as well as treatment strategies and health maintenance. This article covers the non-pregnancy-related issues that are important in caring for women with inflammatory bowel disease. The topics of pregnancy and fertility are covered in a separate review. PMID- 27261901 TI - Obesity in Women: The Clinical Impact on Gastrointestinal and Reproductive Health and Disease Management. AB - Approximately 36% of adult women in the United States are obese. Although obesity affects women similarly to men in terms of prevalence, there seem to be gender specific differences in the pathophysiology, clinical manifestations, and treatment of obesity. Obesity is linked to comorbid diseases involving multiple organ systems, including the gastrointestinal tract, like gastroesophageal reflux disease, fatty liver disease, and gallstones. This article focuses on obesity in women, specifically the impact of obesity on gastrointestinal diseases and reproductive health, as well as the treatment of obesity in women. PMID- 27261902 TI - Metabolic Bone Disease in Primary Biliary Cirrhosis. AB - Primary biliary cirrhosis (PBC) is a liver-specific autoimmune disease that primarily affects women (female-to-male ratio, 10:1) between 40 and 60 years of age. Metabolic bone disease is a common complication of PBC, affecting 14% to 52% of patients, depending on the duration and severity of liver disease. The osteoporosis seen in PBC seems mainly due to low bone formation, although increased bone resorption may contribute. Treatment of osteoporosis consists primarily of antiresorptive agents. Additional large prospective, long-term studies in patients with PBC are needed to determine efficacy in improving bone density as well as reducing fracture risk. PMID- 27261903 TI - Women with Cirrhosis: Prevalence, Natural History, and Management. AB - Cirrhosis is less frequent in women than in men, in large part due to the lower prevalence of hepatitis B, hepatitis C, and alcohol use in women. The most common causes of cirrhosis among women are hepatitis C, autoimmune etiologies, nonalcoholic steatohepatitis, and alcoholic liver disease. For most chronic liver diseases, the risk of progression to cirrhosis and rates of liver failure and hepatocellular carcinoma are lower in women than in men. Pregnancy is very infrequent in women with cirrhosis due to reduced fertility, but when it occurs, requires specialized management. PMID- 27261904 TI - Hepatitis B in the Female Population. AB - Chronic hepatitis B infection in the female population has implications not just for the individual but for her children as well. This article discusses the natural history of hepatitis B and how it plays an important role in hepatitis B virus (HBV) transmission, the current strategies and new strategies to control HBV and reduce transmission, and the updated guidelines for the management of HBV. PMID- 27261905 TI - View from the Top: Perspectives on Women in Gastroenterology from Society Leaders. AB - Women are making great strides at all levels of medicine, including gastroenterology. The proportion of women members in gastroenterology societies has increased nearly 2-fold and the percent of women trainees is 36%. Although there continue to be challenges for women in academic and community practice, the American Gastroenterological Association, American Society of Gastrointestinal Endoscopy, and other gastroenterology societies have dedicated substantial resources to foster careers of women in gastroenterology and develop women as leaders in our societies. This article outlines ongoing challenges for women in gastroenterology and some key initiatives addressing barriers to success. PMID- 27261906 TI - Women's Gastrointestinal Health in 2016: An Introduction to an Expanding Field in Gastroenterology. PMID- 27261907 TI - Epidemiology of Lung Cancer. AB - Lung cancer has been transformed from a rare disease into a global problem and public health issue. The etiologic factors of lung cancer become more complex along with industrialization, urbanization, and environmental pollution around the world. Currently, the control of lung cancer has attracted worldwide attention. Studies on the epidemiologic characteristics of lung cancer and its relative risk factors have played an important role in the tertiary prevention of lung cancer and in exploring new ways of diagnosis and treatment. This article reviews the current evolution of the epidemiology of lung cancer. PMID- 27261908 TI - Classification and Pathology of Lung Cancer. AB - Advancement in the understanding of lung tumor biology enables continued refinement of lung cancer classification, reflected in the recently introduced 2015 World Health Organization classification of lung cancer. In small biopsy or cytology specimens, special emphasis is placed on separating adenocarcinomas from the other lung cancers to effectively select tumors for targeted molecular testing. In resection specimens, adenocarcinomas are further classified based on architectural pattern to delineate tissue types of prognostic significance. Neuroendocrine tumors are divided into typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma based on a combination of features, especially tumor cell proliferation rate. PMID- 27261909 TI - Screening for Lung Cancer. AB - Lung cancer is a global health burden and is among the most common and deadliest of all malignancies worldwide. The goal of screening programs is to detect tumors in earlier, curable stages, consequently reducing disease-specific mortality. The issue of screening has great relevance to thoracic surgeons, who should play a leading role in the debate over screening and its consequences. The burden is on thoracic surgeons to work in a multidisciplinary setting to guide and treat these patients safely and responsibly, ensuring low morbidity and mortality of potential diagnostic or therapeutic interventions. PMID- 27261910 TI - Bronchoscopy: Diagnostic and Therapeutic for Non-Small Cell Lung Cancer. AB - The bronchoscope has gone through much advancement from its origin as a thin metal tube. It has become a highly sophisticated tool for clinicians. Both rigid and the flexible bronchoscopes are invaluable in the diagnosis and treatment of non-small cell lung cancer. Treatment of this disease process hinges on accurate diagnosis and lymph node staging. Technologies, such as endobronchial ultrasound, navigational bronchoscopy, and autofluorescence, have improved efficacy of endobronchial diagnosis and sample collection. If a patient is not a candidate for surgery and has a complication from a centrally located mass, the bronchoscope has been used to deliver palliative therapies. PMID- 27261911 TI - Mediastinal Staging in Non-Small Cell Lung Cancer. AB - In the absence of distant metastases, lung cancer treatment is determined by the results of mediastinal lymph node staging. Occult mediastinal lymph node metastases can be missed by radiologic and needle-based staging methods. Aggressive staging of mediastinal lymph nodes improves staging accuracy. Improved accuracy of mediastinal lymph node staging results in more appropriate lung cancer treatment. Improved accuracy of mediastinal lymph node staging can improve stage-specific survival from lung cancer. PMID- 27261912 TI - Thoracoscopic Lobectomy for Non-small Cell Lung Cancer. AB - Lobectomy is the gold standard treatment in operable patients with surgically resectable non-small cell lung cancer. Thoracoscopic lobectomy has emerged as an option for surgeons facile with the technique. Video-assisted thoracoscopic surgery (VATS) is used for a variety of indications, but its efficacy as a reliable oncologic procedure makes it appealing in the treatment of non-small cell lung cancer. Fewer postoperative complications and decreased postoperative pain associated with VATS procedures can lead to shorter lengths of stay and lower overall costs. Thoracoscopic surgery continues to evolve, and uniportal, robot-assisted, and awake thoracoscopic procedures have all shown promising results. PMID- 27261913 TI - Robotic Lung Resection for Non-Small Cell Lung Cancer. AB - Robotic-assisted pulmonary lobectomy can be considered for patients able to tolerate conventional lobectomy. Contraindications to resection via thoracotomy apply to patients undergoing robotic lobectomy. Team training, familiarity with equipment, troubleshooting, and preparation are critical for successful robotic lobectomy. Robotic lobectomy is associated with decreased rates of blood loss, blood transfusion, air leak, chest tube duration, length of stay, and mortality compared with thoracotomy. Robotic lobectomy offers many of the same benefits in perioperative morbidity and mortality, and additional advantages in optics, dexterity, and surgeon ergonomics as video-assisted thoracic lobectomy. Long-term oncologic efficacy and cost implications remain areas of study. PMID- 27261914 TI - Pneumonectomy for Non-Small Cell Lung Cancer. AB - Lung cancer is the leading cause of cancer deaths and its incidence continues to increase. Emerging therapies as part of a multimodal approach are making more patients eligible for surgical resection. As more surgeons are treating locally advanced non-small cell lung cancer they find themselves recommending pneumonectomy as the surgical component of the multidisciplinary plan. Performing a pneumonectomy is technically demanding and is associated with many potential perioperative comorbidities. With the proper preparation, experience, and attention to perioperative care, pneumonectomy can be carried out safely with excellent outcomes and a good quality of life. PMID- 27261915 TI - Stereotactic Body Radiotherapy and Ablative Therapies for Lung Cancer. AB - The treatment paradigm for early stage lung cancer and oligometastatic disease to the lung is rapidly changing. Ablative therapies, especially stereotactic body radiation therapy, are challenging the surgical gold standard and have the potential to be the standard for operable patients with early stage lung cancer who are high risk due to co- morbidities. The most commonly used ablative modalities include stereotactic body radiation therapy, microwave ablation, and radiofrequency ablation. PMID- 27261916 TI - Neoadjuvant Therapy in Non-Small Cell Lung Cancer. AB - Locally advanced (stage IIIA) non-small cell lung cancer (NSCLC) is confined to the chest, but requires more than surgery to maximize cure. Therapy given preoperatively is termed neoadjuvant, whereas postoperative therapy is termed adjuvant. Trimodality therapy (chemotherapy, radiation, and surgery) has become the standard treatment regimen for resectable, locally advanced NSCLC. During the past 2 decades, several prospective, randomized, and nonrandomized studies have explored various regimens for preoperative treatment of NSCLC. The evaluation of potential candidates with NSCLC for neoadjuvant therapy as well as the currently available therapeutic regimens are reviewed. PMID- 27261917 TI - Adjuvant Therapy for Stage I and II Non-Small Cell Lung Cancer. AB - Patients with stage I and stage II non-small cell lung cancer undergoing complete resection have a 40% to 70% 5-year overall survival despite optimal local therapy. Chemotherapy administered after complete resection has been shown to improve overall survival at 5 years by approximately 5%. This improvement in survival may be confined to patients with stage IB disease 4 cm or greater, and to those with hilar or mediastinal lymph node involvement. The optimal chemotherapy regimen appears to be cisplatin-based doublet or triplet chemotherapy for 3 to 4 cycles. The addition of biologic agents has failed to improve outcomes. PMID- 27261918 TI - Targeted Therapy and Immunotherapy for Lung Cancer. AB - Targeted therapy and immunotherapy have changed the treatment paradigm of non small cell lung cancer (NSCLC). Distinct molecular subtypes of NSCLC have been described over the past 20 years, enabling the emergence of treatments specific to that subtype. Agents targeting the driver mutations in NSCLC have revolutionized the approach to patients with metastatic disease, because oncologists now select a treatment based on the profile of that particular tumor. More recently, an understanding of immune checkpoints has led to the development of checkpoint inhibitors that enable the host immune system to better recognize tumor cells as foreign and to destroy them. PMID- 27261919 TI - Local Therapy Indications in the Management of Patients with Oligometastatic Non Small Cell Lung Cancer. AB - Advances in surgical, radiation, and interventional radiology therapies carry a reduction in morbidity associated with therapy. Aggressive management of patients with oligometastatic non-small cell lung cancer offers the potential for improved disease-free survival and quality of life compared with traditional systemic therapy alone. PMID- 27261920 TI - Lung Cancer. PMID- 27261921 TI - Lung Cancer. PMID- 27261923 TI - Size and thickness effect on creep behavior in conventional and vitamin E diffused highly crosslinked polyethylene for total hip arthroplasty. AB - Since the early 2000s, the use of large femoral heads is becoming increasingly popular in total hip arthroplasty (THA), which provides an improved range of motion and joint stability. Large femoral heads commonly necessitate to be coupled with thinner acetabular liners than the conventionally used because of the limited sizes of outer shells (especially for patients with small pelvic size). However, the influence of the liner thinning on the mechanical performance is still not clearly understood. The objective of this study was to experimentally clarify the size and thickness effect on the rates of compressive creep strain in conventional (virgin low-crosslinked) and vitamin E-diffused highly crosslinked, ultra-high molecular weight polyethylene (UHMWPE) acetabular liners. We applied uniaxial compression to these liners of various internal diameters (28, 32 and 36mm) and thicknesses (4.8, 6.8 and 8.9mm) up to 4320min under the constant load of 3000N. Vitamin E-diffused highly crosslinked UHMWPE components showed significantly greater creep resistance than the conventional ones. In the both types of UHMWPE, the rates of creep strain significantly decreased by increasing the internal diameter and thickness. Varying the component thickness contributed more largely to the creep behavior rather than the internal diameter. Our results suggest the positive mechanical advantage of using large femoral heads, but at the same time, a considerable liner thinning is not recommended for minimizing creep strain. Therefore, the further in-vitro as well as in-vivo research are necessary to conclude the optimal balance of head diameter and liner thickness within the limited sizes of outer shells. PMID- 27261922 TI - Executive functioning and diabetes: The role of anxious arousal and inflammation. AB - Individuals who perform poorly on measures of the executive function of inhibition have higher anxious arousal in comparison to those with better performance. High anxious arousal is associated with a pro-inflammatory response. Chronically high anxious arousal and inflammation increase one's risk of developing type 2 diabetes. We sought to evaluate anxious arousal and inflammation as underlying mechanisms linking inhibition with diabetes incidence. Participants (N=835) completed measures of cognitive abilities, a self-report measure of anxious arousal, and donated blood to assess interleukin-6 (IL-6) and glycated hemoglobin (HbA1c). Individuals with low inhibition were more likely to have diabetes than those with high inhibition due to the serial pathway from high anxious arousal to IL-6. Findings remained when entering other indicators of cognitive abilities as covariates, suggesting that inhibition is a unique cognitive ability associated with diabetes incidence. On the basis of our results, we propose several avenues to explore for improved prevention and treatment efforts for type 2 diabetes. PMID- 27261924 TI - Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections detected by real-time PCR among individuals reporting sexual assaults in the Paris, France area. AB - BACKGROUND: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are the most common bacteria involved in sexually transmitted infections (STIs). In France, combined screening for CT and NG using nucleic acid amplification tests is recommended in populations that are considered at risk. However, no data have been published about victims of sexual assaults. The aim of this retrospective study was to assess the usefulness of real-time PCR for the rapid detection of CT and NG genomic DNA, and the prevalence of CT/NG infections in a sample of sexual assault victims examined at a department of forensic medicine. METHODS: Between July 2012 and July 2013, 326 adults and adolescents aged over 12 years reported a sexual assault and they were referred to the Department of Forensic Medicine for a medical and forensic examination. Secretions from urogenital (cervix or vagina), anorectal, or pharyngeal sites were collected for CT/NG assays. RESULTS: CT and NG were detected in 48/326 (15%) and 16/326 patients (5%), respectively, where 10 (3%) had a CT/NG co-infection. Among 48 patients with CT infection, 13 (27.1%) patients had co-occurring genital and anorectal infections. For the pharyngeal sites, 3/21 men (14.3%) were NG-positive. CONCLUSIONS: Given the high prevalence of CT and NG infections, systematic screening of both pathogens at the time of forensic examination should provide an opportunity for the early treatment of diagnosed STIs. PMID- 27261925 TI - Do more intelligent brains retain heightened plasticity for longer in development? A computational investigation. AB - Twin studies indicate that the heritability of general cognitive ability - the genetic contribution to individual differences - increases with age. Brant et al. (2013) reported that this increase in heritability occurs earlier in development for low ability children than high ability children. Allied with structural brain imaging results that indicate faster thickening and thinning of cortex for high ability children (Shaw et al., 2006), Brant and colleagues argued higher cognitive ability represents an extended sensitive period for brain development. However, they admitted no coherent mechanistic account can currently reconcile the key empirical data. Here, computational methods are employed to demonstrate the empirical data can be reconciled without recourse to variations in sensitive periods. These methods utilized population-based artificial neural network models of cognitive development. In the model, ability-related variations stemmed from the timing of the increases in the non-linearity of computational processes, causing dizygotic twins to diverge in their behavior. These occurred in a population where: (a) ability was determined by the combined small contributions of many neurocomputational factors, and (b) individual differences in ability were largely genetically constrained. The model's explanation of developmental increases in heritability contrasts with proposals that these increases represent emerging gene-environment correlations (Haworth et al., 2010). The article advocates simulating inherited individual differences within an explicitly developmental framework. PMID- 27261927 TI - Neural correlates of retaliatory and prosocial reactions to social exclusion: Associations with chronic peer rejection. AB - Social exclusion is a distressing experience and can lead to both retaliatory and prosocial reactions toward the sources of exclusion. The way people react to social exclusion has been hypothesized to be shaped through chronic exposure to peer rejection. This functional Magnetic Resonance Imaging study examined associations between chronic peer rejection and retaliatory (i.e. punishing) and prosocial (i.e. forgiving) reactions to social exclusion and the neural processes underlying them. Chronically rejected (n=19) and stably highly accepted adolescents (n=27) distributed money between themselves and unknown others who previously included or excluded them in a virtual ball-tossing game (Cyberball). Decreasing the excluders' monetary profits (i.e., punishment) was associated with increased activity in the ventral striatum, dorsolateral prefrontal cortex (PFC) and parietal cortex in both groups. Compared to stably highly accepted adolescents, chronically rejected adolescents exhibited higher activity in the dorsal striatum and lateral prefrontal cortex - brain regions implicated in cognitive control - when they refrained from punishment and shared their money equally with (i.e. forgave) the excluders. These results provide insights into processes that might underlie the maintenance of peer rejection across development, such as difficulties controlling the urge to retaliate after exclusion. PMID- 27261928 TI - Effects of suboccipital release with craniocervical flexion exercise on craniocervical alignment and extrinsic cervical muscle activity in subjects with forward head posture. AB - BACKGROUND: Forward head posture is a head-on-trunk malalignment, which results in musculoskeletal dysfunction and neck pain. To improve forward head posture, both the craniocervical flexion exercise and the suboccipital release technique have been used. OBJECTIVES: The purpose of this study was to compare the immediate effects of craniocervical flexion exercise and suboccipital release combined with craniocervical flexion exercise on craniovertebral angle, cervical flexion and extension range of motion, and the muscle activities of the sternocleidomastoid, anterior scalene, and splenius capitis during craniocervical flexion exercise in subjects with forward head posture. METHODS: In total, 19 subjects (7 males, 12 females) with forward head posture were recruited using G power software. Each subject performed craniocervical flexion exercise and suboccipital release combined with craniocervical flexion exercise in random order. After one intervention was performed, the subject took a 20min wash out period to minimize any carry-over effect between interventions. Craniovertebral angle, cervical flexion and extension range of motion, and the muscle activities of the sternocleidomastoid, anterior scalene, and splenius capitis were measured. A one-way, repeated-measures ANOVA was used to assess differences between the effects of the craniocervical flexion exercise and suboccipital release combined with craniocervical flexion exercise interventions in the same group. RESULTS: Craniovertebral angle (p<0.05), cervical flexion range of motion (p<0.05), and cervical extension range of motion (p<0.001) were significantly greater after suboccipital release combined with craniocervical flexion exercise compared to craniocervical flexion exercise alone. The muscle activities of the sternocleidomastoid, anterior scalene, and splenius capitis were significantly lower during suboccipital release combined with craniocervical flexion exercise than during craniocervical flexion exercise alone across all craniocervical flexion exercise phases except the first (all p<0.05). CONCLUSION: The addition of suboccipital release to craniocervical flexion exercise provided superior benefits relative to craniocervical flexion exercise alone as an intervention for subjects with forward head posture. PMID- 27261926 TI - Mu desynchronization during observation and execution of facial expressions in 30 month-old children. AB - Simulation theories propose that observing another's facial expression activates sensorimotor representations involved in the execution of that expression, facilitating recognition processes. The mirror neuron system (MNS) is a potential mechanism underlying simulation of facial expressions, with like neural processes activated both during observation and performance. Research with monkeys and adult humans supports this proposal, but so far there have been no investigations of facial MNS activity early in human development. The current study used electroencephalography (EEG) to explore mu rhythm desynchronization, an index of MNS activity, in 30-month-old children as they observed videos of dynamic emotional and non-emotional facial expressions, as well as scrambled versions of the same videos. We found significant mu desynchronization in central regions during observation and execution of both emotional and non-emotional facial expressions, which was right-lateralized for emotional and bilateral for non emotional expressions during observation. These findings support previous research suggesting movement simulation during observation of facial expressions, and are the first to provide evidence for sensorimotor activation during observation of facial expressions, consistent with a functioning facial MNS at an early stage of human development. PMID- 27261929 TI - Blood pressure response to six-minute walk test in hypertensive subjects exposed to high altitude: effects of antihypertensive combination treatment. PMID- 27261930 TI - Effectiveness and Safety of Bivalirudin During Percutaneous Coronary Intervention in Acute Coronary Syndrome in the Real World: CARTAGOMAX Study. AB - The CARTAGOMAX study assessed the safety and efficacy of bivalirudin during real world cardiac intervention. This was a single-center prospective study. Patients with acute coronary syndrome undergoing percutaneous coronary intervention were anticoagulated with bivalirudin alone or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor. Propensity score matching was performed to control for baseline imbalances and yielded 1168 patients. There was lower incidence of the composite outcome of death from any cause or major bleeding at 30 days (P = 0.005), 6 months (P = 0.005), and 12 months (P = 0.001) of follow-up in the bivalirudin group, compared with the heparin plus glycoprotein inhibitor group. The administration of bivalirudin was associated with lower rate of all cause mortality at 1 year of follow-up (P = 0.009). The incidence of major bleeding was lower in the bivalirudin group at 1, 6, and 12 months of follow-up (P = 0.002, P = 0.013 and P = 0.017, respectively). The incidence of stroke and reinfarction were similar between groups during follow-up. The rate of stent thrombosis were slightly higher in the bivalirudin group, without reaching statistical significance at 1 and 12 months of follow-up (P = 0.06, P = 0.04, P = 0.07 at 1, 6, and 12 months, respectively). The CARTAGOMAX study found that the use of bivalirudin during percutaneous coronary intervention was associated with lower incidence of the composite outcome of death from any cause or major bleeding during follow-up. The use of bivalirudin was associated with similar rates of stroke, reinfarction, and stent thrombosis compared with heparin plus glycoprotein inhibitor. Bivalirudin proved to be a safe and effective anticoagulant during percutaneous coronary intervention. PMID- 27261931 TI - Assessment and consequences of cell senescence in atherosclerosis. AB - PURPOSE OF REVIEW: Cell senescence is a major process regulating tissue mass, architecture and function, and underlies many diseases of ageing. Recent studies have elucidated some of the regulatory pathways leading to cell senescence, and senescence has also been found in the vasculature. However, assessment of cell senescence is problematic, and the effects of vascular cell senescence are in most cases unproven. The present article will review how senescence is assessed, how it is regulated, where senescence has been described, and the role of cell senescence in atherosclerosis. RECENT FINDINGS: Senescence results in expression of multiple proteins, both intracellular and secreted. However, to date, none of these are specific for senescence, and multiple markers must be used together for positive identification. Despite these shortfalls, cell senescence is detectable in the vasculature in ageing and in human atherosclerosis, and recent studies in mice have indicated that cell senescence promotes both atherogenesis and multiple features of 'vulnerable' lesions in advanced atherosclerotic plaques. SUMMARY: The almost ubiquitous presence of cell senescence in atherosclerosis and the fundamental role of senescence in regulating plaque development and stability suggest that prevention or amelioration of senescence in atherosclerosis is a viable therapeutic target. PMID- 27261932 TI - Subglottic Hemangioma. PMID- 27261933 TI - Role of Transbronchial Needle Core Biopsy in the Diagnosis of Mediastinal Diseases: Experience With an Innovative Endoscopic Technique Using a Rigid Tru Cut Needle. AB - BACKGROUND: Enlarged lymph nodes or mediastinal masses diagnosed by computed tomographic scan before the advent of bronchoscopic procedures (TBNA or EBUS) were usually investigated using a thoracic surgical approach. In this paper, we report the experience with the use of a modified rigid tru-cut needle in the bioptical approach to mediastinal masses; to determine whether it could be considered a valid alternative to surgery, we investigated the diagnostic accuracy of this new endoscopic technique. METHODS: A total of 156 selected patients with radiographic evidence of lymphadenopathy or mediastinal masses (subcarinal and paratracheal with a short-axis diameter >3 cm) were studied in our center by rigid bronchoscopy using a 18-G tru-cut needle to obtain a core biopsy of the lesion. RESULTS: In 140 of 156 cases (89.7%), a histologically correct diagnosis was reached without perioperative or postoperative complications. A total of 114 (81.4%) malignant and 26 (18.6%) benign lesions were diagnosed avoiding further invasive surgical approach. CONCLUSIONS: Our results confirm that, in selected cases, transbronchial rigid core biopsy could be considered a safe and valid alternative technique to more invasive surgical approach in the diagnosis of mediastinal diseases. PMID- 27261934 TI - Intrapulmonary Recombinant Factor VII as an Effective Treatment for Diffuse Alveolar Hemorrhage: A Case Series. AB - BACKGROUND: The diffuse alveolar hemorrhage (DAH) syndrome is a life-threatening pulmonary complication related to systemic vasculitides, posthematopoietic stem cell transplantation, drugs, or toxins. Once DAH develops, the mortality rate is as high as 50% to 80%. Initial treatment consists of high-dose steroids and supportive measures, including mechanical ventilation. We present a case series of 6 patients treated with intrapulmonary recombinant factor VIIa (rFVIIa) to treat refractory DAH. METHODS: Six patients with DAH were treated with intrapulmonary instillation of rFVIIa. Doses were divided equally between the right and the left lungs. Doses were 30, 50, or 60 mcg/kg and frequencies varied from a single administration to repeated doses on subsequent days on the basis of the clinical response. All patients received high-dose steroids, and 4 also received an aminocaproic acid infusion. RESULTS: Intrapulmonary rVFIIa treated DAH effectively in 5 of 6 patients. Doses used were smaller and less frequent than those described previously. CONCLUSIONS: Intrapulmonary factor VII is an effective adjunctive treatment for DAH. We achieved treatment success with both smaller and less frequent doses than those described previously. This may be a good therapeutic option for DAH, particularly when standard therapies have failed or bleeding is immediately life threatening. It is possible that intrapulmonary rFVIIa could save costs, while improving the intensive care unit length of stay. Further prospective studies are needed to assess the optimal dose and frequency for adequate therapeutic efficacy. PMID- 27261935 TI - Site of Bronchoalveolar Lavage Via Flexible Bronchoscopy and Fluid Return in Children. AB - BACKGROUND: Despite its widespread use as a diagnostic tool, the procedure for bronchoalveolar lavage (BAL) via flexible bronchoscopy is not standardized in children. Our objective was to examine the dissimilarities in fluid return between the different lobes in children undergoing flexible bronchoscopies with BAL. METHODS: We conducted a review of all pediatric flexible bronchoscopies with BAL conducted at a single institution over a 2-year period. Our predictor of interest was the site of the BAL. Our outcome of interest was the percent of fluid return. We used 1-way analysis of variance with subsequent pairwise comparisons for unadjusted analyses and multivariable linear regression for adjusted analyses. RESULTS: We identified 529 procedures that met prespecified criteria. The mean (SD) percent of fluid return was 52.1 (14.4) for the right middle lobe, 50.7 (16.0) for the lingula (LIN), 50.5 (18.6) for the right or left upper lobes other than LIN (R/L-UL), and 42.2 (18.7) for the right or left lower lobes (R/L-LL). The R/L-LL had significantly lower fluid return when compared with each of the other lobes (P<0.05 for all pairwise comparisons); in contrast, there was no significant difference in fluid return between the other lobes. In our main analysis adjusting for potential confounders, performing the BAL in the right middle lobe, LIN, or R/L-UL increased the fluid return by 11.1% [95% confidence interval (CI), 6.2-16.1], 9.5% (95% CI, 3.2-15.8), and 8.7% (95% CI, 0.9-16.5%), respectively, when compared with the R/L-LL. CONCLUSION: Our results suggest that the lower lobes provide the lowest BAL fluid return in children, whereas the other lobes seem to perform similarly. PMID- 27261936 TI - Topical Lidocaine Does Not Exaggerate Laryngomalacia in Infants During Flexible Bronchoscopy Under Propofol Anesthesia. AB - BACKGROUND: Topical lidocaine has been found to result in overestimation of the severity of laryngomalacia in infants undergoing flexible bronchoscopy under conscious sedation with midazolam and nalbuphine. This effect has never been confirmed and may depend on the level of sedation and the drugs used. We assessed the effect of topical lidocaine on laryngomalacia in infants undergoing flexible bronchoscopy under general anesthesia with propofol. METHODS: Thirteen infants with congenital stridor referred to diagnostic flexible video-bronchoscopy were studied under propofol anesthesia before and 3 minutes after topical lidocaine administration to the larynx at a dose of 3 mg/kg body weight. Laryngomalacia was scored using 60 seconds video recordings of the larynx before and after lidocaine administration in random order by 2 independent blinded observers using the previously described arytenoid score (AS), epiglottis score (ES), and the total score (TS=AS+ES). RESULTS: No significant differences in AS, ES, and laryngomalacia score were found between the prelidocaine and postlidocaine assessments by the 2 raters. The intraclass correlation coefficients were 0.995 (95% confidence interval, 0.986-0.998) and 0.975 (0.930-0.991) and 0.989 (0.971 996) for AS, ES, and TS, respectively. CONCLUSIONS: The assessment of laryngomalacia is not affected by topical lidocaine under propofol anesthesia. The lidocaine effect on laryngomalacia may vary depending on the medication regime used and the depth of procedural sedation. PMID- 27261937 TI - Transbronchial Cryobiopsy in Interstitial Lung Disease: Are We on the Right Path? AB - BACKGROUND: A definitive and specific diagnosis of interstitial lung disease (ILD) often requires a histologic analysis of the lung parenchyma. A transbronchial biopsy with forceps has a limited diagnostic yield for idiopathic interstitial pneumonias. The incorporation of a transbronchial lung cryobiopsy for diagnosing ILD appears to be very promising, although there are only a few published studies in this regard. Our paper shows the results of using this technique in our center. METHODS: This was a prospective study including 55 patients with ILD diagnosed from January 2012 to January 2015. The methodology used, the overall diagnostic yield, and the number and the location of samples, in addition to complications, have been reported. RESULTS: In 38 (69%), 10 (20.8%), and 7 (12.7%) cases, we obtained a certain, highly likely, and unclassifiable diagnosis of interstitial pneumonia, respectively. With 18 cases, usual interstitial pneumonia was the most common diagnosis. The most common complication was a pneumothorax in 8 patients (14.5%). CONCLUSIONS: A transbronchial lung cryobiopsy using a flexible cryoprobe has a good diagnostic yield and might be an alternative to consider in cases of diffuse ILD in which a histologic sample is required for diagnosis. This technique could avoid a large number of surgical biopsies. PMID- 27261938 TI - Air Bubble-Induced High Intraocular Pressure After Descemet Membrane Endothelial Keratoplasty. AB - PURPOSE: To investigate the incidence and risk factors of pupillary block caused by an air bubble in the anterior chamber in the early postoperative period after Descemet membrane endothelial keratoplasty (DMEK). METHODS: A retrospective review was conducted in 306 eyes that underwent DMEK from September 2009 through October 2014 at the Tubingen Eye Hospital. Intraocular pressure (IOP) elevation was defined as a spike above 30 mm Hg. In the first 190 eyes, an intraoperative peripheral iridectomy was performed at the 12-o'clock position and in the other 116 eyes at the 6-o'clock position. If possible, reasons for IOP elevation were identified. For all eyes, preoperative and postoperative slit-lamp examinations and IOP measurements were performed. RESULTS: Overall, 30 eyes (9.8%) showed a postoperative IOP elevation within the first postoperative day. The incidence of IOP elevation was 13.9% (5/36) in the triple DMEK group, and 2 of 5 phakic eyes (40%) developed an air bubble-induced IOP elevation. All eyes presented with a de novo IOP elevation, associated in 25 patients with pupillary block from air anterior to iris and in 5 patients with angle closure from air migration posterior to the iris. All of them had an iridectomy at the 12-o'clock position. CONCLUSIONS: A postoperative pupillary block with IOP elevation caused by the residual intraoperative air bubble may be an important complication that could be avoided by close and frequent observations, especially in the first postoperative hours and by an inferior peripheral iridectomy and an air bubble with a volume of <=80% of the anterior chamber. PMID- 27261939 TI - Diurnal Tracking of Blink and Relationship to Signs and Symptoms of Dry Eye. AB - PURPOSE: To assess diurnal changes in the signs and symptoms of dry eyes and their relationship to diurnal interblink interval (IBI) in normal subjects and in subjects with dry eye. METHODS: Blink data were collected from 9:00 AM to 8:00 PM during 2 days of normal activity using an electrocardiogram monitoring device. All subjects recorded ocular discomfort (0-5 scale) and primary activity hourly each day in a diary. Inferior and central fluorescein staining was graded by slit lamp (0-4) at the start and end of each day. Blink activity was detected using an algorithm based on recognition of the waveform corresponding to the kinematic properties of the blink signal. RESULTS: Normal subjects (N = 12) reported negligible symptoms, and results did not show a diurnal change in group hourly IBI. Mean daily IBI for the group with dry eye (N = 15) (4.63 +/- 1.63 s) was shorter than that for the normal group (5.28 +/- 1.48 s) (P = 0.0483). Correlation of diurnal symptoms and mean hourly IBI was relatively weak (r = 0.248). A repeated-measures model found IBI to be significantly associated with the time of day (P = 0.0028). Inferior corneal staining showed a small but significant diurnal increase for both normal group and group with dry eyes. CONCLUSIONS: Diurnal blink tracking reveals significant trending with symptoms. Diurnal change in IBI may be an appropriate surrogate for symptoms in the study of dry eye. PMID- 27261940 TI - Tolerance of Micronized Mineral Pigments for Intrastromal Keratopigmentation: A Histopathology and Immunopathology Experimental Study. AB - PURPOSE: To study the tolerance and biocompatibility of mineral pigments for corneal pigmentation histopathologically and immunologically in an experimental animal model. METHODS: Manual intralamellar keratopigmentation was performed in 28 New Zealand white rabbits using micronized mineral pigments. Histopathological examination was performed 3 months after the surgery to determine the level of pigment diffusion, the level of inflammation, and the presence/absence of neovascularization. An immunological analysis was also performed. RESULTS: No pigment diffusion or changes in color, inflammation, or neovascularization were detected in the treated eyes. Histopathological examination corroborated clinical results regarding inflammation. Pigmented corneas showed a good cosmetic appearance without signs of ocular toxicity. From the immunological perspective, the pigments do not generate an inflammatory response in the rabbit cornea or in vitro. CONCLUSIONS: Micronized mineral pigments could be a valid alternative treatment for corneal pigmentation. Manual intralamellar keratopigmentation technique presented good cosmetic appearance without adverse effects in the treated eyes. PMID- 27261941 TI - Partial Lamellar Sclerokeratouvectomy for Management of Epithelial Downgrowth. AB - PURPOSE: To describe a method of surgical management for cases of localized epithelial downgrowth (EDG). METHODS: Single-center retrospective chart review of patients with histologically confirmed localized EDG of stratified squamous epithelium. Each patient underwent a partial lamellar sclerokeratouvectomy encompassing the area of suspected EDG. The main outcome measure was recurrence of EDG. RESULTS: At a mean of 51 months of postoperative follow-up (range: 31 86), no patient had evidence of recurrent EDG. One eye developed worsening of preexisting glaucoma. All 3 eyes developed localized corneal edema, but only 1 required corneal transplantation. CONCLUSIONS: EDG is a potentially devastating complication of intraocular surgery or penetrating injury. In cases of localized involvement of the anterior chamber structures, definitive management of EDG can be achieved via resection of the involved scleral, corneal, and uveal tissue. A lamellar approach minimizes tissue loss and maintains a structurally sound, pressurized globe. PMID- 27261942 TI - Update in alar base reduction in rhinoplasty. AB - PURPOSE OF REVIEW: The purpose of this article is to further explore the techniques available for alar base reduction by a recent review in this topic, focusing in the current advances in the field, in a clear and readable format. RECENT FINDINGS: Among the numerous techniques available, the management of cases with wide nasal base and alar flaring remains limited to three options: cinching sutures to pull in the alae together; or to use alar base excisions that remove tissue from the alar lobule to decrease flare and from inside the nostril to decrease width; and flap advancement. SUMMARY: Surgical modification of the nasal base is not a routine part of rhinoplasty and should be performed in a conservative manner to prevent complications like nasal stenosis. Moreover, this maneuver should always be the last one in rhinoplasty, as alar base modifications cannot be properly assessed until all other steps have been carried out. VIDEO ABSTRACT. PMID- 27261943 TI - Simulation in craniomaxillofacial training. AB - PURPOSE OF REVIEW: Simulation in healthcare is no longer a novel idea. Simulation continues to rapidly permeate and transform both clinical practice and medical education. Craniomaxillofacial surgery is comprised of multiple surgical disciplines, including neurosurgery, plastic surgery, otolaryngology, ophthalmology, and oral and maxillofacial surgery. All of these specialties are performing surgery in an era of evolving technology, cost containment, reduced resident work hours, and a focus on patient safety. As a result, the purpose of this manuscript is to review the most recent literature and trends in craniomaxillofacial surgery simulation as it pertains to advances in: teaching methodology, technology for training, and professional development, including lifelong learning and certificate maintenance. RECENT FINDINGS: The Halstedian model of education is no longer valid in isolation as simulation continues to evolve. Advances are occurring in craniomaxillofacial simulation fidelity, via technology, validation, and implementation, though significant opportunity still exists toward total integration into training, as procedural models are limited. SUMMARY: Simulation in craniomaxillofacial training is not fully pervasive or integrated, but evidence exists that simulation is rapidly evolving via improvements in innovation, fidelity, teaching methodology, and ultimately, commitment to simulation as a means to improve surgical education as well as patient safety and quality. PMID- 27261944 TI - New biomaterials versus traditional techniques: advances in cleft palate reconstruction. AB - PURPOSE OF REVIEW: Cleft lip and palate still remains one of the most common congenital anomalies, and consequently surgical correction of these anomalies is still commonplace. Despite numerous existing surgical techniques having good outcomes, it is still recognized that the morbidity of certain surgical procedures and success rates regarding outcomes can be improved. The purpose of this review is to evaluate new literature and techniques compared with the time tested procedures that are commonly used. RECENT FINDINGS: As technology continues to advance, the understanding of details regarding biochemical pathways responsible for the development of cleft defects and also the efficacy of biomaterials that can be used in their correction are being discovered and better understood. Many studies have been conducted in both animal and human study participants that further the understanding of these questions. The efficacy and benefit of newly devised biomaterials seems to indicate that these biomaterials are a viable adjunct and often an alternative in the treatment of cleft palate patients. SUMMARY: In this review of recent literature, the discussion begins with a review of the more traditional and widely accepted iliac crest bone grafting and then evolves into a discussion of several animal and human studies to delineate the progress being made in this field. The literature exploring the details regarding biochemical pathways and cellular mediators that are involved in cleft formation, as well as biomaterials used in surgical repair are evaluated. The findings in the literature suggest that there is a bright future in better understanding the cause of cleft formation on a molecular level and associated attempts that can be made in altering some of these factors along with discovering new biomaterials that can be a useful adjunct to existing techniques. PMID- 27261945 TI - Advances in eyelid reconstruction. AB - PURPOSE OF REVIEW: To describe the principles of eyelid reconstruction that must balance aesthetic and functional concerns of one of the most important areas of physical beauty on the human body. Our review seeks to give an overview of how to utilize a variety of techniques along the reconstructive ladder from direct closure to complex grafts and local flaps. RECENT FINDINGS: We describe novel modifications of existing flaps that have been traditionally used in eyelid reconstruction along with analysis of many time honored techniques and current research in improving our understanding of the factors which allow a successful reconstruction. SUMMARY: A familiarity with the variety of options for reconstruction will give the surgeon the fluidity to analyze a defect and choose the best possible method. PMID- 27261946 TI - Central Retinal Artery Occlusion With Subsequent Central Retinal Vein Occlusion in Biopsy-Proven Giant Cell Arteritis. AB - Central retinal artery occlusion with subsequent central retinal vein occlusion in the same eye is a rare entity. We present a 72-year-old man with biopsy-proven giant cell arteritis who developed bilateral arteritic anterior ischemic optic neuropathy and a left central retinal artery occlusion. Subsequently, he developed a left central retinal vein occlusion within 2 weeks of his initial vision loss. His vision did not improve with corticosteroids. PMID- 27261947 TI - Idiopathic Intracranial Hypertension-A Comparison of Clinical Characteristics Between 4 Medical Centers in Different Geographic Regions of the World. AB - BACKGROUND: Idiopathic intracranial hypertension (IIH) is a well-characterized syndrome, most commonly affecting obese women of childbearing age. Differences in its prevalence have been reported in various populations. The aim of this article was to determine whether differences in clinical presentation and management exist for patients with IIH between different regions the world. METHODS: Retrospective database analysis of adult patients with IIH from 4 different neuro ophthalmology clinics. The data collected included gender, age of onset, body mass index (BMI), lumbar puncture opening pressure, initial visual acuity (VA), initial visual field (VF) mean deviation (MD), pharmacological or surgical treatment, length of follow-up, final VA, and final VF MD. RESULTS: The study population consisted of 244 patients, with significant regional variations of female to male ratio. Overall, there was no significant difference regarding the age of diagnosis or the BMI. Acetazolamide was the first line of treatment in all groups but there was a difference between countries regarding second-line treatment, including the use of surgical interventions. Mean initial VA differed between groups but the final change in VA was the same among all the study groups. CONCLUSIONS: There are differences in IIH presentation, treatment, and response to therapy among different countries. International prospective studies involving multiple centers are needed to determine the potential influence of environmental and genetic factors on the development of IIH and to improve the management of this potentially blinding disorder. PMID- 27261948 TI - Dyschromatopsia in Multiple Sclerosis Patients: A Marker of Subclinical Involvement? AB - BACKGROUND: In multiple sclerosis (MS), even in the absence of a clinical episode of optic neuritis (ON), the optic nerve and retinal nerve fiber layer (RNFL) may be damaged leading to dyschromatopsia. Subclinical dyschromatopsia has been described in MS associated with lower motor and cognitive performances. OBJECTIVES: To set the prevalence of dyschromatopsia in eyes of MS patients without a history of ON, to compare its prevalence in patients with and without ON history, and to explore the association between dyschromatopsia and disease duration, average peripapillary RNFL thickness, macular volume, and cognitive and motor performances. METHODS: An observational cross-sectional study was conducted at multiple medical centers. Data were collected after single neurological and ophthalmological evaluations. Dyschromatopsia was defined by the presence of at least 1 error using Hardy-Rand-Rittler plates. RESULTS: In our population of 125 patients, 79 patients (63.2%) never had ON and 35 (28.8%) had unilateral ON. The prevalence of dyschromatopsia in eyes of patients without ON was 25.7%. Patients with dyschromatopsia had a statistically significant lower RNFL thickness (P = 0.004 and P = 0.040, right and left eyes, respectively) and worse performance in symbol digit modalities test (P = 0.012). No differences were found in macular volume or motor function tasks. CONCLUSIONS: Dyschromatopsia occurs frequently in MS patients. It may be associated with a worse disease status and possibly serve as a marker for the detection of subclinical disease progression since it was detected even in the absence of ON. It correlated with thinner peripapillary RNFL thickness and inferior cognitive performance. PMID- 27261949 TI - Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients. AB - Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08-12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment. PMID- 27261950 TI - Essential and toxic trace element concentrations in different commercial veal cuts in Spain. AB - The aim of this study was to evaluate essential and toxic element concentration of ten commercially available veal cuts, together with diaphragm, cardiac muscle and liver tissue from 10 animals of "Galician Supreme Veal". Essential trace elements (Co, Cr, Cu, Fe, Mn, Mo, Ni, Se and Zn) and toxic elements (As, Cd, Hg and Pb) were determined by ICP-MS. Essential trace element concentrations ranged from 0.002-55.64mg/kg between muscles. Toxic element concentrations were very low, and high numbers of samples showed unquantifiable residues of Cd and Pb. Veal cuts including muscles with a high proportion of oxidative slow-twitch fibers (diaphragm and cardiac muscle) showed significantly higher essential trace element concentrations, the lower concentrations being found in veal cuts including glycolytic fast-twitch fibers (eye round). Our results suggest that essential and toxic trace element concentration could be used as a new meat quality parameter, or to add further value to certain products (i.e. livestock reared on extensive systems with high physical activity). PMID- 27261951 TI - Ethics in practice: is it futile to talk about 'futility'? PMID- 27261952 TI - The Effectiveness of Remote Facilitation in Simulation-Based Pediatric Resuscitation Training for Medical Students. AB - OBJECTIVES: To assess the effectiveness of pediatric simulation by remote facilitation. We hypothesized that simulation by remote facilitation is more effective compared to simulation by an on-site facilitator. We defined remote facilitation as a facilitator remotely (1) introduces simulation-based learning and simulation environment, (2) runs scenarios, and (3) performs debriefing with an on-site facilitator. METHODS: A remote simulation program for medical students during pediatric rotation was implemented. Groups were allocated to either remote or on-site facilitation depending on the availability of telemedicine technology. Both groups had identical 1-hour simulation sessions with 2 scenarios and debriefing. Their team performance was assessed with behavioral assessment tool by a trained rater. Perception by students was evaluated with Likert scale (1-7). RESULTS: Fifteen groups with 89 students participated in a simulation by remote facilitation, and 8 groups with 47 students participated in a simulation by on site facilitation. Participant demographics and previous simulation experience were similar. Both groups improved their performance from first to second scenario: groups by remote simulation (first [8.5 +/- 4.2] vs second [13.2 +/- 6.2], P = 0.003), and groups by on-site simulation (first [6.9 +/- 4.1] vs second [12.4 +/- 6.4], P = 0.056). The performance improvement was not significantly different between the 2 groups (P = 0.94). Faculty evaluation by students was equally high in both groups (7 vs 7; P = 0.65). CONCLUSIONS: A pediatric acute care simulation by remote facilitation significantly improved students' performance. In this pilot study, remote facilitation seems as effective as a traditional, locally facilitated simulation. The remote simulation can be a strong alternative method, especially where experienced facilitators are limited. PMID- 27261953 TI - Streptococcus constellatus Tubo-ovarian Abscess in a Non-Sexually Active Adolescent Female. AB - Tubo-ovarian abscess (TOA) in non-sexually active female adolescents is a rare presentation to the pediatric emergency department. In the following case, bilateral TOA secondary to Streptococcus constellatus was diagnosed in a 13-year old virginal female. The patient was seen 4 months before presentation for interventional radiology-guided drainage and antibiotic treatment for an intra abdominal abscess due to suspected appendiceal rupture. Exploratory laparotomy on the most recent presentation demonstrated an appendix with inflammation and serositis on pathology report, a concern for chronic appendicitis with microperforation and subsequent bacterial translocation of the bilateral ovaries. This case report identifies a rare cause, pathogen, and the patient's demographics presenting with bilateral TOA. Most importantly, this case demonstrates the need for emergency medicine physicians to have a high index of suspicion for TOA in patients with a significant medical history of intra abdominal pathology to promptly diagnose and treat high-morbidity pathology. PMID- 27261954 TI - Efficiency of Using Pediatrics Emergency Services and Triage Evaluation. AB - OBJECTIVE: The aim of the study was to evaluate the pediatric emergency department (PED) in a main teaching hospital. METHOD: Retrospective review of all children presented to PED at King Abdulaziz University Hospital from September to November 2014 was performed. We classified priority into the following 5 stages: 1, need resuscitation; 2, emergent; 3, urgent; 4, less urgent; and 5, nonurgent. RESULTS: A total of 2567 children (58.9% boys) attended PED for 3 months. Toddler age group was the highest. Respiratory complaints were the commonest (36%), followed by gastrointestinal complaints (20%). The majority were classified as priority 3 (52.3%) and priority 4 (30.7%). The admission rate was 12.3% and the mean (range) length of stay (LOS) was 5.85 (0.2-25) hours. Saudi nationals were less likely to wait for 5 hours or longer, less likely to be admitted, but more likely to leave PED without being evaluated. There was a negative correlation between higher priorities and time from triage to PED. There was a positive correlation between the higher priorities and LOS. CONCLUSIONS: Most children who were seen in PED were priority 3 and therefore needed to be seen. However, a considerable percentage of priority 4 and 5 could have been seen in ambulatory clinics. Most lower priorities were Saudi nationals who were most likely to leave without being seen. Prolonged LOS, overcrowding, and high percentage of admission are the main challenges. PMID- 27261955 TI - Factors Predicting Lung Contusions in Critically Ill Trauma Children: A Multivariate Analysis of 330 Cases. AB - PURPOSE: The aim of the study was to identify factors predicting lung contusion in trauma children. METHODS: Retrospective study conducted for a period of 8 years (January 01, 2005-December 31, 2012) in a medical surgical intensive care unit. All trauma patients younger than 15 years were included. Two groups were compared: those with lung contusions (C+ group) and those without lung contusions (C- group). RESULTS: We included 330 patients. The mean (SD) age was 7.6 (4.3) years. Chest injury was diagnosed in 70 patients (21.2%). All our patients needed mechanical ventilation. Lung contusions were diagnosed in 43 patients (13% of all patients and 61.4% of patients with chest trauma). In multivariate analysis, independent factors predicting lung contusion were road traffic accident (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.2-8.6; P = 0.019), increased Pediatric Risk of Mortality (PRISM) score (OR, 1.1; 95% CI, 1.1-1.2; P = 0.017), hepatic contusion (OR, 4.8; 95% CI, 1.3-17.1; P = 0.017), and pelvic ring fracture (OR, 3.5; 95% CI, 1.1-10.5; P = 0.026). Death occurred in 46 patients (13.9%). Intensive care unit mortality was significantly higher in the C+ group (OR, 2.5; 95% CI, 1.2-5.4; P = 0.021). However, mortality was not different between the 2 groups after adjusting for PRISM score (OR, 1.2; 95% CI, 0.5-2.9; P = 0.752) or after adjusting for Injury Severity Score (OR, 0.7; 95% CI, 0.3-2.1; P = 0.565). CONCLUSIONS: Lung contusion is common in critically ill children with chest trauma. The diagnosis should be considered in patients with road traffic accident, increased PRISM score, hepatic contusion, and pelvic ring fracture. PMID- 27261956 TI - Effect of Intravenous Ondansetron on the QT Interval of Patients' Electrocardiograms. AB - OBJECTIVE: Ondansetron improves the success of oral rehydration in children with gastroenteritis. In postoperative adults, ondansetron has been shown to prolong the corrected QT (QTc). The aim of the study was to evaluate the effect of ondansetron on the QT at peak effect and at 1-hour postpeak effect in pediatric patients. METHODS: This was an observational study looking at patients aged 6 months to 18 years receiving intravenous ondansetron for nausea, vomiting, or the inability to take fluids in the emergency department. Patients had electrocardiogram performed at baseline, at ondansetron's peak effect, and 1 hour postpeak effect. A paired samples Student t test compared QTc change at peak effect to zero. Peak effect of intravenous ondansetron is 3 minutes. RESULTS: One hundred patients were included. Fifty-five percent of patients were female with a mean age of 8.3 years. The mean (range) baseline QTc was 435 (388 to 501) milliseconds. The mean (range) change in QTc at peak effect of ondansetron was 3 (-40 to 65) milliseconds (P = 0.072). The change in QTc 1-hour postpeak effect of ondansetron was 3 (-43 to 45) milliseconds (P = 0.082). No change at peak effect or 1-hour postpeak effect was clinically significant. CONCLUSIONS: Ondansetron does not affect the QTc of pediatric patients receiving the medication for nausea, vomiting, or inability to take fluids in the emergency department. No changes in the QTc are clinically significant. To date, there have been no studies evaluating the effect of ondansetron in this acutely ill population; therefore, a larger study should be completed to confirm these data. PMID- 27261957 TI - Pre-Trauma Center Management of Intracranial Pressure in Severe Pediatric Traumatic Brain Injury. AB - OBJECTIVES: Pre-trauma center care is a critical component in severe pediatric traumatic brain injury (TBI). For geographically large trauma catchment areas, optimizing increased intracranial pressure (ICP) management may potentially improve outcomes. This retrospective study examined ICP management in nontrauma centers and during interfacility transport to the trauma center. METHODS: Charts from a pediatric level I trauma center were reviewed for admissions between 2008 and 2013. Patients with a Glasgow Coma Scale score of 8 or less, head Abbreviated Injury Scale score of 3 or higher, and requiring intubation at a nontrauma center were included. Exclusion criteria included head injury secondary to drowning, stroke, obstetrical complications, asphyxia, and afflicted head trauma (younger than 5 years). Trauma center charts contained coalesced data from first responders, nontrauma centers, and transport. RESULTS: Twenty-five patients (74%) had increased ICP upon admission at trauma center, 48% experienced ICPs greater than 20 cm H2O within 12 hours of admission, 12% required an urgent craniotomy, and 16% had herniation syndromes on neuroimaging. Pre-trauma center ICP management included osmotherapy and head-of-bed elevation. Sixty-four percent of patients with increased ICP at trauma center admission received pre-trauma center ICP management. CONCLUSIONS: Early increased ICP is a common presentation of severe pediatric TBI during pre-trauma center management. However, what constitutes optimal care remains unknown. Given the difficulties of diagnosing early increased ICP in this setting, prophylactic raising ICP-lowering strategies may be considered. PMID- 27261958 TI - The "Double Medial Malleolus": A New Physical Finding in Talocalcaneal Coalition. AB - PURPOSE: It has been the observation of the senior author that there is a bony fullness or "double medial malleolus" over the middle facet as a consistent finding with most talocalcaneal coalitions (TCC). To document this observation, we reviewed records and radiographs in 3 patient groups. METHODS: Part 1: retrospective chart review was completed for 111 feet to determine the clinical presence of a palpable "double medial malleolus." Part 2: computed tomography (CT) scans for evaluation of tarsal coalition or symptomatic flatfoot between January 2006 and December 2014 were retrospectively reviewed for the same cohort. Soft tissue thickness was measured as the shortest distance between bone and skin surface at both the medial malleolus and the middle facet/coalition. The volume of the middle facet or coalition was measured at their midpoint. These findings were compared among feet with TCC (n=53), calcaneonavicular coalition (CNC) (n=20), and flatfoot (n=38). RESULTS: Part 1-clinical: from medical records, 38 feet (34%) had documented record of a palpable medial prominence. Of the feet reviewed with a "double medial malleolus," all had TCC (no false positives or false negatives). Clinical and CT prominence demonstrated significant correlation (rs=0.519, P=0.001). Part 2-radiographic: CT observation of "double medial malleolus" is significantly associated with TCC (P<0.001). CT observation of double medial malleolus is 81% sensitive and 79% specific as a predictive test for TCC. The middle facet-to-skin distance was significantly closer in those with TCC versus controls (P<0.001). The ratio was larger in patients with TCC versus CNC (P=0.006) or flatfeet (P<0.001). Volume was nearly twice the size in patients with TCC versus the controls (P<0.001). CONCLUSIONS: TCCs have a bony prominence below the medial malleolus on clinical exam and CT scan not present in flatfeet or CNCs. This abnormal middle facet is almost twice the size of the normal middle facet. Obesity or severe valgus may mask this finding. If a palpable bony prominence is noted just below the medial malleolus during examination of a painful foot with a decrease in subtalar motion, the likely diagnosis is TCC. With this added clinical finding, appropriate images can be ordered to confirm the diagnosis of the latter. We advise CT scans with 3D images for surgical planning. The primary finding for tarsal coalitions in textbooks is decreased subtalar motion. This new finding of a palpable enlarged medial prominence just below the medial malleolus is highly associated with TCCs. LEVEL OF EVIDENCE: Level III. PMID- 27261959 TI - What's New in Pediatric and Adolescent Anterior Cruciate Ligament Injuries? AB - BACKGROUND: Anterior cruciate ligament (ACL) tears in children and adolescent patients are being diagnosed and treated at an ever-increasing rates. We performed a review of recent literature regarding care of children and adolescent athletes with an ACL injury. METHODS: PubMed database was searched for all papers related to treatment of children and adolescents with ACL injuries from October 1, 2012 to September 30, 2015, yielding 114 publications. RESULTS: A total of 59 papers were found to have contributed important new findings. Papers were selected based on new findings in the following categories: epidemiology, anatomy, risk factors, sex disparity, prevention, surgical outcomes, timing and associated pathologies, and rehabilitation and return to sport. CONCLUSIONS: Pediatric ACL injuries continue to rise and there are multiple surgical procedures that restore clinical function with good outcomes. Early surgical treatment is favored to prevent concomitant articular injuries. Early return to play can increase risk of reinjury and should be met with caution in this age group. Prevention strategies should be further studied and implemented in hopes of decreasing the incidence of this injury and the long-term potential damage. LEVEL OF EVIDENCE: Level 4-titerature review. PMID- 27261960 TI - rhBMP-2 and Intramedullary Fixation in Congenital Pseudarthrosis of the Tibia. AB - BACKGROUND: In congenital pseudarthrosis of the tibia, use of intramedullary (IM) fixation and autogenous bone graft has long been the standard of care. This study was undertaken to determine whether the addition of rhBMP-2 to this treatment method further enhances healing potential. METHODS: Twenty-one patients with congenital pseudarthrosis of the tibia were evaluated. Fifteen of these patients had neurofibromatosis type 1 (NF1). All had IM fixation and autogenous bone graft, followed by a BMP-soaked collagen sponge wrapped around both the fracture site and bone graft. A minimum 2 years' follow-up was required. RESULTS: Follow up averaged 7.2 years (range, 2.1 to 12.8 y). Sixteen of 21 tibias achieved bone union following the index surgery, at an average 6.6 months postoperatively. The 5 persistent nonunions occurred in NF1 patients. Further surgery was undertaken in these 5 NF1 patients, including the use of BMP. One of the 5 healed, 1 had persistent nonunion, and 3 eventually had amputation. Of the 16 patients who healed initially following the index surgery, 5 refractured (3 had NF1). Of these 5 patients, the IM fixation at the index surgery did not cross the ankle joint, and refracture occurred at the rod tip in 4. Three of these 5 patients healed following further surgery, 1 had persistent nonunion, and 1 had amputation. All of those with eventual amputation had NF1. No deleterious effects related to the use of BMP-2 were recognized in any patient. CONCLUSIONS: The addition of rhBMP-2 appears to be helpful in shortening the time required to achieve fracture union in those who healed, but its use does not insure that healing will occur. LEVEL OF EVIDENCE: Level IV-therapeutic, case series. PMID- 27261961 TI - Continued Growth of the Femoral Neck Leads to Improved Remodeling After In Situ Fixation of Slipped Capital Femoral Epiphysis. AB - BACKGROUND: Globally, the most common method for in situ fixation of slipped capital femoral epiphysis (SCFE) is a threaded screw, which causes physeal arrest. The standard treatment in Sweden is unthreaded fixation using the Hansson hook-pin, which leads to continued growth of the femoral neck. Our purpose was to study remodeling during the remaining growth after fixation with the Hansson hook pin. METHODS: We performed a retrospective study of 54 patients with SCFE who were treated with the Hansson hook-pin between 2001 and 2009. The immediate postoperative radiograph and the radiograph taken after physeal closure (mean interval, 34 mo) were analyzed. Three radiographic assessments were used: the head-shaft angle (HSA), the alpha angle (Notzli), and the displacement from Klein's line. RESULTS: Significant remodeling was detected in all measured parameters. The mean postoperative HSA decreased by 9.0 degrees (P<0.001). The alpha angle improved by a mean of 14.5 degrees (P<0.001). Significant correlations were found between the reduction of the alpha angle and age (P<0.001, R=0.48) and longitudinal growth of the femoral neck (P<0.001, R=0.67). Displacement from Klein's line increased by a mean of 1.6 mm (P=0.006). CONCLUSIONS: Unthreaded fixation of SCFE using the Hansson hook-pin leads to substantial remodeling of the femoral neck. The positive correlation observed between the improvement of the alpha angle and femoral neck growth supports the use of a method that allows continuous growth, to reduce the risk of femoroacetabular impingement. LEVEL OF EVIDENCE: Level III-retrospective comparative study. PMID- 27261962 TI - Treatment of Pediatric and Adolescent Pelvic Ring Injuries With Percutaneous Screw Placement. AB - BACKGROUND: Pediatric and adolescent pelvic ring injuries are frequently treated without surgery. In patients with unstable injuries to the pelvic ring, surgical stabilization aids in resuscitation, provides pain relief, and allows for mobilization. Percutaneous pelvic screw fixation is commonly performed in adult patients for unstable pelvic ring injuries, but a paucity of literature exists regarding their use in pediatric patients. The purpose of this study is to review the use, outcome, and management of percutaneous posterior pelvic screws in pediatric patients with unstable pelvic ring injuries. METHODS: A retrospective review of a prospectively collected orthopaedic trauma database was performed over a 7-year period at a regional level-1 trauma center. All patients between the ages of 7 and 17 who sustained an injury to the pelvic ring and were treated with percutaneous fixation of the posterior pelvic ring were identified. We evaluated the frequency of this technique in the described patient population, incidence of nerve injury, infection, loss of fixation, and need for hardware removal. RESULTS: A total of 238 pediatric patients who sustained a pelvic ring injury were initially identified; following application of study criteria, 67 (28.1%) patients were included in the study. Additional anterior ring fixation was performed in 33 (49.2%) patients. There were no iatrogenic nerve injuries, no infections, and surgical blood loss was <50 mL in all cases. Clinical and radiographic follow-up averaged 33 weeks. No loss of reduction was observed. Eight patients (13%) reported persistent low back pain at last follow-up. Elective hardware removal was performed in 3 patients. CONCLUSIONS: The majority of pediatric pelvic ring injuries can be treated without surgery. In the setting of instability, percutaneous pelvic screw fixation can be performed safely. A computed tomography scan is used to evaluate the available osseous pathways for screws and intraoperative fluoroscopy is used to safely perform this technique. Screw removal should be discussed in select patients. LEVEL OF EVIDENCE: Level IV. PMID- 27261963 TI - Normal Percentile Reference Curves and Correlation of Acetabular Index and Acetabular Depth Ratio in Children. AB - BACKGROUND: Radiographic surveillance of the hip is vital in the diagnosis and treatment of developmental dysplasia of the hip (DDH) in children. The acetabular index (AI) and the acetabular depth ratio (ADR) are radiographic parameters for evaluation of acetabular morphology. Normal reference curves for these parameters that allow for serial evaluation of acetabular development in a manner that is independent of age are necessary and clinically useful. The purpose of this study was (1) to establish normal values of AI and ADR in the normally developing pediatric hip up to age 14, (2) to generate percentile reference curves of both parameters, (3) to determine the extent of correlation between AI and ADR, and (4) to assess intrarater and interrater reliability of AI measurement. METHODS: We identified 1734 patients who underwent anterior-posterior pelvic radiography between 2004 and 2014. A total of 1152 patients (age range, 0.15 to 13.97 y; 2304 hips) were identified as radiographically normal in the radiology report, signed by the attending pediatric radiologist on the basis of the absence of structural deformity of the hip and previously established reference values for DDH assessment. A review of the medical records confirmed that patients had no diagnosis of DDH or any other orthopaedic hip pathology. The AI and ADR were measured in all radiographs. Normal values and fully parametric percentile curves were generated from birth to skeletal maturity. Correlation between AI and ADR was assessed using linear regression analysis. RESULTS: Normal AI decreased, and ADR increased, with age. Percentile curves were generated for AI and ADR. Using the provided equations, measured values can be converted to age-appropriate percentile and Z-score. The 2 parameters exhibited strong correlation (Pearson correlation=-0.789, P<0.001). For every unit increase in ADR, AI decreased by 0.94 degrees. CONCLUSIONS: We present updated normative values of AI that expand up to age 14, and novel reference values for ADR. The reference curves allow for the easy conversion of measured values to percentile and Z-score. Using the presented method during surveillance of the pathologic hip, change in acetabular development can now be assessed in a manner that is independent of age and the natural development of the acetabulum. LEVEL OF EVIDENCE: Level IV-case series. PMID- 27261964 TI - Correction of Angular Deformities Due to Focal Fibrocartilaginous Dysplasia Using Guided Growth: A Preliminary Report. AB - BACKGROUND: Focal fibrocartilaginous dysplasia (FFCD) is a rare benign disorder that may result in tethering of the physis. These most commonly occur around the knee and may result in angular deformities of the involved extremity. To date treatment has ranged from observation, to curettage, to osteotomy. Our goal with this study is to evaluate the efficacy of guided growth in treating patients with angular deformity due to FFCD. METHODS: This is a retrospective review, we included 3 patients with angular deformities due to FFCD who had undergone 8 plate placement. We reviewed their preoperative and postoperative radiographs, assessed their sagittal and coronal balance and number of procedures. RESULTS: Three patients with FFCD of the femur with an average of 14 months underwent guided growth to correct their angular deformity. Once appropriate correction was achieved the hardware was removed. At final follow-up none of the patients required further surgical intervention for their angular deformity nor had they shown any evidence of recurrence. CONCLUSIONS: FFCD is a rare benign disorder, they most commonly affects the proximal tibia and distal femur and can result in significant angular deformities. Our review of the literature found all of the cases involving the femur progressed to the point where they needed surgical intervention. This ranged from curettage to osteotomy. In this case series we present 3 cases of FFCD of the distal femur that were treated minimally invasively with guided growth. LEVEL OF EVIDENCE: Level 4. PMID- 27261965 TI - Performing a Definitive Fusion in Juvenile CP Patients is a Good Surgical Option. AB - BACKGROUND: In juveniles with progressive curves, there is debate regarding the use of growth friendly implants versus definitive fusion. This study presents outcomes of juvenile cerebral palsy (CP) scoliosis patients who underwent definitive fusion before age 11. METHODS: A review of a prospective, multicenter registry identified patients 10 years and younger who had a definitive posterior fusion for their CP scoliosis. Preoperative and postoperative demographic and radiographic changes were evaluated with descriptive statistics. Repeated measures analysis of variance were utilized to compare outcome scores. RESULTS: Fourteen children with a mean age of 9.7 years (8.3 to 10.8 y) and a minimum of 2 years follow-up (range 2 to 3 y) were identified. The mean preoperative curve magnitude and pelvic obliquity was 84+/-25 degrees (range 63 to 144 degrees) and 25+/-14 degrees, respectively. All patients were skeletally immature with open triradiate cartilage. Three patients had unit rods with wires while the rest incorporated pedicle screws. Immediately postoperation, the average major curve was 25+/-17 degrees (P<=0.001, 71% correction rate). At most recent follow-up, the average major curve increased to 30+/-18 degrees (P<=0.001) for a 65% correction rate. Pelvic obliquity improved to 4+/-4 degrees (84% correction, P<=0.001) immediately postoperation and to 6+/-5 degrees (P=0.002) at latest follow-up for a 76% correction rate. None of the patients required revision surgery for progression. From pre to most recent follow-up, the CPchild Health outcome scores improved from 47 to 58 (P=0.019). One patient had a deep infection, and 1 patient had a broken rod that did not require any further treatment. CONCLUSIONS: Progressive scoliosis in juvenile CP patients requires the surgeon to balance the need for further growth with the risks of progression or repeated surgical procedures. Our study demonstrates that definitive fusion once the curves approach 90 degrees results in significant radiographic and quality of life improvements, but further follow-up is needed to determine whether those results remain after skeletal maturity. LEVEL OF EVIDENCE: Level IV therapeutic. PMID- 27261966 TI - Long-term Outcomes of Operative and Nonoperative Treatment of Congenital Coxa Vara. AB - BACKGROUND: Congenital coxa vara (CCV) is a rare hip condition with few long-term studies. The purpose of this study was to assess clinical, radiographic, and functional outcomes after operative and nonoperative treatment of CCV, assess reliability of radiographic parameters, and investigate risk factors for recurrence after surgery. METHODS: Retrospective review was performed of all CCV patients treated at 1 institution from 1980 to 2010. In addition, patients were recalled for additional follow-up x-rays, modified Harris Hip Score (mHHS), and gait analysis. Radiographic measurements [neck-shaft angle (NSA), head-shaft angle (HSA), Hilgenreiner-epiphyseal angle (HEA), and femoral neck length (FNL)] were assessed for reliability using intraclass correlation coefficients. Multivariate analysis was performed to identify risk factors for recurrence after surgery. RESULTS: Forty-six hips in 32 patients were reviewed. Mean age at presentation was 5.4+/-4.9 years. Mean follow-up was 11.8+/-5.8 years. Valgus proximal femoral osteotomy was performed in 27 hips (20 patients). Initial deformity was greater in the operative group (NSA 90+/-17 degrees, HEA 68+/-19 degrees) versus nonoperative patients (NSA 122+/-19 degrees, HEA 34+/-14 degrees) (P<0.0001), but radiographic outcomes were similar at follow-up. Most nonoperative hips had normal FNL growth rates (80%), but resolution of varus NSA occurred in only 21%. In contrast, 56% of operative hips showed decreased FNL growth rates. Interobserver reliability was excellent for HEA (0.98), NSA (0.90), and FNL (0.89), and good for HSA (0.79). Repeat osteotomy was performed in 6 cases (22%). No significant predictors for recurrence were identified. At long term follow-up for recalled patients, 72% had significantly abnormal gait, and 50% had fair-poor functional outcomes (mHHS<79). CONCLUSIONS: Valgus osteotomy corrects severe deformity in CCV with improved clinical and radiographic outcomes. HEA and NSA are the most reliable radiographic measurements of proximal femoral deformity in CCV. Recurrence is not uncommon, but no predictors were identified. Many patients have persistent gait abnormalities and functional impairment at long-term follow-up, regardless of prior treatment. LEVEL OF EVIDENCE: Level III-retrospective cohort. PMID- 27261967 TI - Chronic C1-C2 Rotatory Subluxation Reduced by C1 Lateral Mass Screws and C2 Translaminar Screws: A Case Report. AB - BACKGROUND: C1-C2 rotatory subluxation can result from a variety or etiologies. Pediatric patients are particularly susceptible to C1-C2 rotatory subluxation. If left untreated the condition is termed an atlantoaxial rotatory fixation (AARF) and chronic neck pain and deformity can result. Patients failing conservative treatment or those with recurrent or chronic rotatory subluxation may require halo treatment or surgical intervention. This illustrative case report is about a patient with chronic C1-C2 AARF who was treated with C1 lateral mass screws and C2 translaminar screws, a treatment that has not been addressed by this technique in a pediatric population. METHODS: This is a retrospective case review. RESULTS: After an unsuccessful attempt at reduction, an 11-year-old girl underwent surgery to treat her C1-C2 AARF. Through an all posterior approach, screws were placed bilaterally into the C1 lateral masses followed by the placement of C2 translaminar screws bilaterally. A small amount of distraction was applied through the screw construct to open up the C1-C2 articulation and the AARF was open reduced and fused. A detailed postoperative computed tomographic scan focused on the occiput C1-C2 joint confirmed the anatomical reduction of the joint complex. CONCLUSIONS: The patient had cosmetically pleasing relief of her torticollis and was doing well at 60 months after surgery. LEVEL OF EVIDENCE: Level IV. PMID- 27261968 TI - Age Predicts Disruption of the Articular Surface of the Femoral Condyles in Knee OCD: Can We Reduce Usage of Arthroscopy and MRI? AB - BACKGROUND: The purpose of this study was to determine if patient age could accurately identify disrupted articular cartilage overlying an osteochondritis dissecans (OCD) lesion of the femoral condyle in adolescents. This could have important implications for imaging and treatment decisions. METHODS: All patients from 2001 to 2014 who were arthroscopically treated for a femoral condyle OCD were included in this Institutional Review Board-approved study. Exclusion criteria were trochlear and patellar OCD lesions, idiopathic arthritis, and traumatic osteochondral injuries. Arthroscopy was performed to visualize and probe the articular surface. Arthroscopic and magnetic resonance imaging (MRI) findings were recorded as "intact" or "disrupted" cartilage. Extra-articular drilling was performed when the articular cartilage was intact. RESULTS: There were 119 patients (81 male, 68%) with 139 OCD lesions in 136 knees. The mean age at time of surgery was 13.0 years (range, 7.2 to 19.3 y). At arthroscopy, 115 knees had intact cartilage and 24 had disrupted cartilage. There was a significant difference in age between patients with intact versus disrupted cartilage at arthroscopy (12.5 vs. 15.3 y; P<0.0001). Eighty-eight OCD lesions had MRIs preoperatively, showing 69 as intact and 19 (24%) disrupted. MRI reading for cartilage status had 94% sensitivity and 97% specificity. Multivariable regression analysis revealed that age (P<0.01) and MRI status (P<0.0001) were strong predictors of cartilage status. Sixteen years was the critical age in which both sensitivity was maximized and false positive probability was minimized. Over the age of 17 years, 7 of 7 (100%) had disrupted cartilage. Age alone was 100% sensitive for children below the age of 10, and 96% sensitive below the age of 13. CONCLUSIONS: Age was a good predictor of cartilage status in both younger (<13 y) and older (>=17 y) patients in this study. For patients in the mid-range group (13 through 16 y), age alone is not an adequate predictor of cartilage status, but adding MRI increased accuracy. SIGNIFICANCE: Age can be used to stratify patients and thereby influence diagnostic and treatment strategies. LEVEL OF EVIDENCE: Level IV. PMID- 27261969 TI - Incidence of and Risk Factors for Loss of 1 Blood Volume During Spinal Fusion Surgery in Patients With Cerebral Palsy. AB - BACKGROUND: Spinal fusion surgery is associated with greater blood loss in patients with cerebral palsy (CP) than in patients with adolescent idiopathic scoliosis. Risk factors for loss of 1 blood volume (LOBV) in patients with CP have not been well studied. We investigated the incidence of and risk factors for LOBV during spinal fusion surgery in young patients with CP. METHODS: We queried a multicenter registry of CP patients for all patients 21 years or younger who had undergone spinal fusion from 2008 through 2013; 272 patients met these criteria. We analyzed data on patient characteristics, preoperative laboratory values, radiographic measures, and surgical characteristics. For univariate analysis, we used chi tests and logistic regression models. Factors that were significant in the univariate analysis were used to construct a multivariate logistic regression model. Significance was set at P<0.01. RESULTS: Incidence of LOBV was 39.7%. On multivariate analysis, unit rod construct and coronal curve magnitude were significantly associated with LOBV (P<0.01). The multivariate model accounted for 32.2% of variance in LOBV. Compared with patients with pedicle screw-rod constructs, patients with unit rod constructs had 12.6-fold higher odds of LOBV (P<0.01). For each 1-degree increase in coronal curve magnitude, odds of LOBV increased 1.03-fold (P<0.01). CONCLUSIONS: In patients with CP, there is a substantial risk of LOBV during spinal fusion surgery. Use of unit rod constructs and greater preoperative coronal curves were significant risk factors for LOBV during surgery. LEVEL OF EVIDENCE: Level II. PMID- 27261970 TI - Early MRI Detection and Closed Bone Graft Epiphysiodesis May Alter the Course of Avascular Necrosis Following Unstable Slipped Capital Femoral Epiphysis. AB - BACKGROUND: Unstable slipped capital femoral epiphysis (SCFE) has an increased incidence of avascular necrosis (AVN). Early identification and surgical intervention for AVN may help preserve the femoral head. METHODS: We retrospectively reviewed 48 patients (50 hips) with unstable SCFE managed between 2000 and 2014. AVN was diagnosed based on 2 different postoperative protocols. Seventeen patients (17 hips) had a scheduled magnetic resonance imaging (MRI) between 1 and 6 months from initial surgery, and the remaining 31 patients (33 hips) were evaluated by plain radiographs alone. If AVN was diagnosed, we offered core decompression and closed bone graft epiphysiodesis (CBGE) to mitigate its affects. At final follow-up, we assessed progression of AVN using the Steinberg classification. RESULTS: Overall 13 hips (26%) with unstable SCFEs developed AVN. MRI revealed AVN in 7 of 17 hips (41%) at a mean of 2.5 months postoperatively (range, 1.0 to 5.2 mo). Six hips diagnosed by MRI received surgical intervention (4 CBGE, 1 free vascularized fibula graft, and 1 repinning due to screw cutout) at a mean of 4.1 months (range, 1.3 to 7.2 mo) postoperatively. None of the 4 patients treated with CBGE within 2 months postoperatively progressed to stage IVC AVN. The 2 patients treated after 4 months postoperatively both progressed to stage VC AVN.Plain radiographs demonstrated AVN in 6 of 33 hips (18%) at a mean of 6.8 months postoperatively (range, 2.1 to 21.1 mo). One patient diagnosed with stage IVB AVN at 2.4 months had screw cutout and received CBGE at 2.5 months from initial pinning. The remaining 5 were not offered surgical intervention. Five of the 6 radiographically diagnosed AVN, including the 1 treated with CBGE, progressed to stage IVC AVN or greater. CONCLUSIONS: Although all patients with positive MRI scans developed radiographic AVN, none of the 4 patients treated with CBGE within 2 months after pinning developed grade IVC or greater AVN. Early MRI detection and CBGE may mitigate the effects of AVN after SCFE. LEVEL OF EVIDENCE: Level III-retrospective comparative study. PMID- 27261971 TI - Clinical and Radiographic Outcomes After Submuscular Plating (SMP) of Pediatric Femoral Shaft Fractures. AB - BACKGROUND: To evaluate lower extremity strength and alignment among children who underwent submuscular plating (SMP). METHODS: Subjects who underwent SMP for a length unstable femoral fracture returned for isokinetic strength testing >=2 years after surgery. Extensor and flexor strength deficits (percent difference) between the operative and nonoperative limbs were evaluated. Radiographic measurements of mechanical alignment [anatomic lateral distal femoral angle (aLDFA)] and qualitative measurements (The Pediatric Outcomes Data Collection Instrument, PODCI) were obtained from all subjects. The upper 97.5% confidence interval approach to establishing clinical equivalency was utilized to compare differences in strength and alignment between the operative and nonoperative limbs. An extensor strength deficit of >19% and an aLDFA discrepancy of >5 degrees were considered to be clinically significant. RESULTS: The average age at surgery of the 10 subjects included in the study was 8.7 years. The hardware was placed an average of 27.9 mm from the distal femoral physis and was removed 6.4 months postsurgery. Among all subjects, the median PODCI scores were >=97 according to all subscales. There was no significant difference in extension torque between the operative versus nonoperative limbs at 60 degrees/s (P=0.5400), 120 degrees/s (P=0.4214), or 180 degrees/s (P=0.8166). More importantly, extension strength deficits between the operative and nonoperative limbs were not clinically significant at 60 degrees/s [upper 97.5% confidence interval (CI), 10.9%], 120 degrees/s (upper 97.5% CI, 11.0%), or 180 degrees/s (upper 97.5% CI, 10.7%). The difference in aLDFA between the operative and nonoperative limb was less than the predefined clinically significant threshold of 5 degrees for all subjects. CONCLUSIONS: SMP achieves satisfactory clinical and functional results. In this series, extensor strength deficits and/or lower extremity malalignment were not clinically meaningful. High patient satisfaction can be expected after implant removal. LEVEL OF EVIDENCE: Level IV-case series. PMID- 27261972 TI - Detection of Femoral Neck Fractures in Pediatric Patients With Femoral Shaft Fractures. AB - BACKGROUND: Ipsilateral femoral neck fractures occur in 1% to 9% of adult trauma patients with femoral shaft fractures making dedicated imaging important. This is not as clear in children. Our purpose is to establish the incidence of ipsilateral femoral neck fractures in children with femoral shaft fractures and to provide recommendations regarding diagnostic imaging protocols. METHODS: A retrospective analysis of medical records was performed for pediatric patients (below 18 y) with femoral shaft fractures seen at our trauma center over a 10 year period. Mechanism of injury, associated injuries, procedures, and follow-up data were collected, and all radiographs reviewed. Exclusion criteria included peri-implant fractures or evidence of pathologic fracture. A similar retrospective analysis was performed in a cohort of adult patients. RESULTS: Of 267 pediatric patients with femoral shaft fractures, 2 patients (0.7%) had ipsilateral femoral neck fractures. One femoral neck fracture was detected on initial plain radiographs and the other on a pelvic computed tomography (CT) scan. Both of these fractures resulted from high-energy trauma, which accounted for 92 (42%) of pediatric femoral shaft fractures. The cohort of 100 adults aged 18 to 89 years with femoral shaft fractures revealed 6 adult patients (6%) with ipsilateral femoral neck fractures, all from high-energy trauma. High-energy trauma accounted for 85% of the adult femoral shaft fractures, and was more common than in the pediatric population (P<0.005). The difference in incidence of ipsilateral femoral neck fracture between the pediatric (0.7%) and the adult group (6%) was significant (P=0.007). No missed or delayed diagnoses were identified. CONCLUSIONS: The incidence of associated ipsilateral femoral neck fracture in pediatric patients with femoral shaft fracture is very low (0.7%). Most (58%) pediatric femur fractures are caused by low-energy trauma. We were unable to demonstrate a need for routine CT scanning of the femoral neck in children with femoral shaft fractures. Given the increased risks of radiation exposure with younger and smaller patients, it does not appear that routine CT scanning low-energy pediatric femoral shaft fractures to evaluate for femoral neck fractures is justified unless there is a high level of clinical suspicion. LEVEL OF EVIDENCE: Level II. PMID- 27261974 TI - Novel sequence variations in the thymidine phosphorylase gene causing mitochondrial neurogastrointestinal encephalopathy. PMID- 27261973 TI - Mutations in the Na(+)/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay. AB - Mutations in the SLC13A5 gene that codes for the Na(+)/citrate cotransporter, NaCT, are associated with early onset epilepsy, developmental delay and tooth dysplasia in children. In the present study we identify additional SLC13A5 mutations in nine epilepsy patients from six families. To better characterize the syndrome, families with affected children answered questions about the scope of illness and treatment strategies. There are currently no effective treatments, but some anti-epileptic drugs targeting the GABA system reduce seizure frequency. Acetazolamide, a carbonic anhydrase inhibitor and atypical anti-seizure medication decreases seizures in 4 patients. In contrast to previous reports, the ketogenic diet and fasting produce worsening of symptoms. The effects of the mutations on NaCT transport function and protein expression were examined by transient transfections of COS-7 cells. There was no transport activity from any of the mutant transporters, although some of the mutant transporter proteins were present on the plasma membrane. The structural model of NaCT suggests that these mutations can affect helix packing or substrate binding. We tested various treatments, including chemical chaperones and low temperatures, but none improve transport function in the NaCT mutants. Interestingly, coexpression of NaCT and the mutants results in decreased protein expression and activity of the wild-type transporter, indicating functional interaction. In conclusion, our study has identified additional SLC13A5 mutations in patients with chronic epilepsy starting in the neonatal period, with the mutations producing inactive Na(+)/citrate transporters. PMID- 27261975 TI - Effects of mindfulness-based therapy for patients with breast cancer: A systematic review and meta-analysis. AB - OBJECTIVE: To quantify the effects of mindfulness-based therapy (MBT) on physical health, psychological health and quality of life (QOL) in patients with breast cancer. METHOD: Studies were identified through a systematic search of six electronic databases. Randomized control trials (RCTs) examining the effects of MBT, versus a control group receiving no intervention on physical health, psychological health and QOL in breast cancer patients were included. Two authors independently assessed the methodological quality of included studies using a quality-scoring instrument developed by Jadad et al. and extracted relevant information according to a predesigned extraction form. Data was analysed using the Cochrane Collaboration's Revman5.1. RESULT: Finally, seven studies involving 951 patients were included. While limited in power, the results of meta-analysis indicated a positive effect of MBT in reducing anxiety [SMD -0.31, 95% CI -0.46 to -0.16, P<0.0001], depression[SMD -1.13, 95% CI -1.85 to -0.41, P=0.002], fear of recurrence[SMD -0.71, 95% CI -1.05 to -0.38, P<0.0001], and fatigue[SMD -0.88, 95% CI -1.71 to -0.05, P=0.04] associated with breast cancer, and improving emotional well-being [SMD 0.39, 95% CI 0.19-0.58, P=0.0001], physical function[SMD 0.42, 95% CI 0.19-0.65, P=0.0004], and physical health [SMD 0.31, 95% CI 0.08-0.54, P=0.009] in these patients. Although the effects on stress, spirituality, pain and sleep were in the expected direction, they were not statistically significant (P>0.05). Moreover, there is limited evidence from a narrative synthesis that MBT can improve QOL of breast cancer patients. CONCLUSION: The present data indicate that MBT is a promising adjunctive therapy for patients with breast cancer. Due to some methodological flaws in the literature, further well-designed RCTs with large sample sizes are needed to confirm these preliminary estimates of effectiveness. PMID- 27261976 TI - A systematic review of acupuncture for sleep quality in people with insomnia. AB - OBJECTIVE: Acupuncture is widely used in Asia and increasingly in Western countries. We performed a systematic review and meta-analysis to examine the effects of acupuncture for insomnia. METHODS: We identified randomized controlled trials from English and Chinese databases. Data were extracted using a predefined form and analysed using RevMan 5.2. We included studies that compared acupuncture to sham/placebo, standard pharmacotherapy or cognitive behavioral therapy. Risk of bias was assessed using the Cochrane risk of bias tool. The primary outcome was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: A total of 30 studies involving 2363 participants were included. Acupuncture point combinations included the use of at least one of the recommended points for insomnia, HT7, GV20, SP6. Pharmacotherapy control was used in 27 studies and sham/placebo in three studies. Cognitive behavioral therapy was not used in any of the studies. Pharmacotherapies in all studies were benzodiazepine receptor agonists, except for one that used an antidepressant. Acupuncture was superior to sham/placebo in terms of PSQI (MD -0.79, 95% CI -1.38, -0.19, I(2)=49%). Acupuncture was also more effective than pharmacotherapy (MD -2.76, 95% CI -3.67, -1.85, I(2)=94%). Most studies were at risk of bias. Some mild adverse events were reported but they were not causally related to the acupuncture treatments. CONCLUSIONS: Acupuncture compared to sham/placebo and pharmacotherapy showed statistically significant results. However, the evidence is limited by bias in the included studies and heterogeneity. Well-designed studies are needed to confirm the results identified in this review. PMID- 27261977 TI - Oral Chinese herbal medicine in combination with phototherapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials. AB - AIMS: The aim of this study was to assess the effects of oral Chinese herbal medicine (CHM) combined with phototherapy for vitiligo. METHODS: We undertook a meta-analysis of relevant randomized controlled trials (RCTs) and searched eight bibliographic databases from inception to December 2015. RESULTS: A total of 5 RCTs with 513 participants which assessed the efficacy of oral CHM in combination with narrow-band ultraviolet B (NB-UVB) in treating vitiligo were included. The meta-analysis revealed a superior effectiveness in those receiving oral CHM plus NB-UVB when compared to phototherapy alone (risk difference 0.22, 95% confidence interval 0.14 to 0.29, P<0.00001). Only mild adverse events were reported without significant renal or liver function impairment. CONCLUSIONS: The current evidence demonstrates that oral CHM in combination with NB-UVB has a superior effectiveness in terms of repigmentation rate of vitiligo when compared to NB-UVB alone. Although the overall quality of included trials was low, oral CHM in combination with NB-UVB may be an alternative option of treatment for vitiligo. As to safety, there were only mild adverse events reported without significant renal or liver function impairment. However, there is limited available evidence of long-term follow-up and poor methodological quality of the available trials. Well-designed RCTs of adequate length and sample size that include life quality as an outcome are warranted. PMID- 27261978 TI - Traditional Chinese Medicine acupuncture and myofascial trigger needling: The same stimulation points? AB - BACKGROUND: Acupuncture originates in China, and its effectiveness has been well documented in musculoskeletal pain disorders and other conditions. A widely accepted contemporary medical treatment option for myofascial pain is trigger point needling. Although there are many differences between Traditional Chinese Medicine acupuncture theory and the myofascial trigger point needling framework, it is argued that the stimulation sites for these two needling modalities are similar. DISCUSSION: In this paper we examined the correspondence between Traditional Chinese Medicine acupoints and myofascial trigger points. Based on this correspondence, we considered exploration of Ah-shi points from four aspects: pain recognition, distal Ah-shi points, Anti-Ah-shi points, and management approaches. SUMMARY: The extent of correspondence is influenced by definitions of acupoints. Myofascial trigger points are significantly correlated to Traditional Chinese Medicine acupoints, including primary channel acupoints, extra acupoints, and Ah-shi points. Considering the correlation between MTrPs and acupoints and the rarely-studied research area of Ah-shi points, it may be reasonable to incorporate research findings of myofascial trigger points into further investigations into Ah-shi points. Correspondence between myofascial trigger points and acupoints enhances contemporary understanding of the mechanism of action of acupuncture, and may serve to facilitate increased integration of acupuncture into clinical management. PMID- 27261979 TI - Effects of progressive muscle relaxation on cerebral activity: An fMRI investigation. AB - OBJECTIVES: Progressive muscle relaxation (PMR) is one of the self-management relaxation techniques that can be used in the general population and patients with specific issues. However, no study to date has revealed the brain activity associated with PMR. Therefore, we assessed the changes in brain activity induced by PMR using functional magnetic resonance imaging (fMRI). DESIGN AND SETTING: We conducted an intervention study with PMR and control sessions. The subjects were twelve healthy adult men who had no prior experience of PMR. INTERVENTIONS: Subjects performed a control session in which muscles were repeatedly simply tensed and relaxed. Subsequently, a PMR session took place, during which muscle tension was reduced through a systematic procedure of tensing and relaxing of muscle groups combined with structured breathing. MAIN OUTCOME MEASURES: We identified and visualised brain activity based on individual and group-level analysis of fMRI data. RESULTS: Eleven subjects' data were analysed. In the control session, brain activity broadly changed, while the change was limited to specific parts of the cerebral cortex and limbic system in the PMR session. PMR gradually decreased activity in the superior frontal gyrus (SFG), inferior frontal gyrus (IFG), and posterior cingulate cortex (PCC). In a region of interest (ROI) analysis, interactions between sessions were observed in the putamen, anterior cingulate cortex (ACC), postcentral gyrus (PCG), and insula. CONCLUSIONS: That PMR led to few areas showing changed activity suggests that the technique may suppress brain activity. Even novices may be able to induce such a focused mental state. PMID- 27261980 TI - The effects of footbath on sleep among the older adults in nursing home: A quasi experimental study. AB - OBJECTIVES: To examine the long-term effects of foot-bathing therapy, using different water temperatures, on the sleep quality of older adults living in nursing homes. DESIGN: A quasi-experimental study design with non-equivalent control group. SETTINGS: Thirty participants were recruited from a nursing home in Gyeong-gi Province, South Korea. INTERVENTIONS: The participants were randomly assigned to experimental, placebo, and control groups. The foot-bathing therapy was performed for 30min daily for four weeks. Water at 40 degrees C was used for the experimental group, while water at 36.5 degrees C was used for the placebo group. The control group did not receive any intervention. MAIN OUTCOME MEASURES: The participants' sleep patterns (total sleep amount, sleep efficiency, and sleep latency) and sleep-disturbed behaviors were compared based on group, using actigraphy and a sleep disorder inventory. RESULTS: The total amount of sleep and sleep efficiency were significantly different for the experimental group, especially those with poor sleep quality. There were no differences in sleep latency or sleep-disturbed behaviors among the groups. The long-term effect of the therapy decreased in the third week of the therapy. CONCLUSIONS: Daily, 30 min foot-bathing therapy sessions with water at 40 degrees C were effective in improving sleep quality for older adults. The therapy was more effective for participants with poor sleep quality at baseline assessment than those with relatively good sleep quality. The long-term effects of foot-bathing therapy decreased three weeks after initiation; therefore, it might be desirable to deliver the therapy for two weeks, pause it for a week, and then resume it. PMID- 27261981 TI - Effect of oil pulling in promoting oro dental hygiene: A systematic review of randomized clinical trials. AB - AIM: To critically appraise and evaluate the evidence from randomized clinical trials (RCTs) examining the effectiveness of oil pulling on oro dental hygiene. METHODS: We conducted electronic searches in Medline, Embase, Amed, The Cochrane Library and Cinahl databases from inception to February 2015, and assessed reporting quality using the Cochrane risk of bias criteria. We included RCTs that compared oil pulling using conventional cooking oils with a control intervention. Our primary outcomes were measures of oro dental hygiene using validated scales. RESULTS: Electronic searches yielded 26 eligible studies, of which five RCTs comprising a total of 160 participants were included. The studies varied in reporting quality, lasted between 10 and 45 days, and compared oil pulling with chlorhexidine, placebo or routine dental hygiene practice. Three studies reported no significant differences in post intervention plaque index scores between oil pulling and control groups (Chlorhexidine mouthwash +/- Placebo): p=0.28, 0.94, and 0.38, respectively. Two studies reported no significant difference in post intervention modified gingival index score between oil pulling and Chlorhexidine mouthwash groups (p=0.32 and 0.64). CONCLUSION: The limited evidence to date from clinical trials suggests that oil pulling may have beneficial effects on oro dental hygiene as seen for the short period of time investigated. Given that this is a potentially cost-effective intervention, this practice might be of particular benefit. Future clinical trials should be more rigorous and better reported. PMID- 27261982 TI - Synergistic effect of moxibustion and rehabilitation training in functional recovery of post-stroke spastic hemiplegia. AB - OBJECTIVE: To evaluate the therapeutic benefit of combining moxibustion and rehabilitation training for functional recovery in post-stroke spastic hemiplegic patients. METHODS: We randomly divided 84 cases subjecting to inclusion criteria into moxibustion plus rehabilitation training group (MRT group, n=44) and rehabilitation training group (RT group, n=40). Evaluation of therapeutic effect was observed before treatment, 2 weeks during treatment and 6 months after treatment. Spasticity was evaluated using modified Ashworth scale (MAS) and Clinical Spasticity Index (CSI), recovery of motor function was assessed by Brunnstrom recovery stages and Simplified Fugl-Meyer Motor Scale, and performance of activities of daily living (ADL) was measured, and the quality of life was assessed by Patient Reported Outcomes (PRO). RESULTS: Evaluation of upper limbs, hands and lower limbs based on CSI and MAS revealed significant improvements in patients treated with MRT, compared to RT alone, both during and after therapy. CSI and MAS also showed significant improvement in patients at each time point in the MRT group, compared to RT group. Marked improvement in Fugl-Meyer Motor Scale was also observed in MRT group at each time point. Based on Brunnstrom grades of upper limbs, hands and lower limbs, significant differences between the two groups were recorded at all time points during and after therapy. Barthel index (BI) and PRO also confirmed the dramatic differences between the two therapy groups. CONCLUSIONS: Our results demonstrate that combination therapy with moxibustion and rehabilitation training offers greater clinical benefits in relieving spasticity, promoting function recovery of motion, improving the performance of ADL, and increasing quality of life in post-stroke spastic hemiplegic patients, compared to RT alone. PMID- 27261983 TI - Auricular acupuncture diagnosis in patients with lumbar hernia. AB - BACKGROUND: Auricular Acupuncture Diagnosis is a diagnostic method which is essential for the topographic identification on the auricle of the anatomical parts of the body carrying a particular ailment or dysfunction. OBJECTIVE: To identify the specific zones related to lumbar hernia in patients treated with a series of epidural infiltrations with corticosteroids. METHODS: In a consecutive group of thirty patients with lumbar hernia 2 diagnostic methods used in Auricular Acupuncture Diagnosis, Pain Pressure Test and Electric Skin Resistance Test, were applied before the first infiltration (T0), before the second and the third infiltration (T1, T2) and one week after the third infiltration (T3). The parameters, whose variations were analyzed at T0-T3, were the following: the number of points identified; the intensity of pain on a verbal rating scale and the foot-hand distance in cm with bent spine and extended knees. The identified points were reported on the Auricular Sectogram which is a validated graphic system suitable for a correct transcription of the points and indicated for a statistical analysis of their distribution on the different sectors. RESULTS: A significant association was found for some auricular areas, along the series of epidural infiltrations, with a progressive reduction in the number of tender and low electrical resistance points together with a decrease of pain and hand-foot distance. CONCLUSIONS: The auricular zones found with Auricular Acupuncture Diagnosis in our group of patients seem of clinical relevance and could be included in the complementary treatment of lumbar-sciatic pain in lumbar hernia. PMID- 27261985 TI - Osteopathic manipulative treatment in gynecology and obstetrics: A systematic review. AB - OBJECTIVE: The aim of the review was to evaluate the effects of the osteopathic manipulative treatment (OMT) on women with gynaecological and obstetric disorders. MATERIALS AND METHODS: An extensive search from inception to April 2014 was conducted on MEDLINE, Embase, the Cochrane library using MeSH and free terms. Clinical studies investigating the effect of OMT in gynaecologic and obstetric conditions were included as well as unpublished works. Reviews and personal contributions were excluded. Studies were screened for population, outcome, results and adverse effects by two independent reviewers using an ad-hoc data extraction form. The high heterogeneity of the studies led to a narrative review. RESULTS: 24 studies were included (total sample=1840), addressing back pain and low back functioning in pregnancy, pain and drug use during labor and delivery, infertility and subfertility, dysmenorrhea, symptoms of (peri)menopause and pelvic pain. Overall, OMT can be considered effective on pregnancy related back pain but uncertain in all other gynaecological and obstetrical conditions. Only three studies (12.5%) mentioned adverse events after OMT. CONCLUSIONS: Although positive effects were found, the heterogeneity of study designs, the low number of studies and the high risk of bias of included trials prevented any indication on the effect of osteopathic care. Further investigation with more pragmatic methodology, better and detailed description of interventions and systematic reporting of adverse events are recommended in order to obtain solid and generalizable results. PMID- 27261984 TI - A yoga & exercise randomized controlled trial for vasomotor symptoms: Effects on heart rate variability. AB - OBJECTIVES: Heart rate variability (HRV) reflects the integration of the parasympathetic nervous system with the rest of the body. Studies on the effects of yoga and exercise on HRV have been mixed but suggest that exercise increases HRV. We conducted a secondary analysis of the effect of yoga and exercise on HRV based on a randomized clinical trial of treatments for vasomotor symptoms in peri/post-menopausal women. DESIGN: Randomized clinical trial of behavioral interventions in women with vasomotor symptoms (n=335), 40-62 years old from three clinical study sites. INTERVENTIONS: 12-weeks of a yoga program, designed specifically for mid-life women, or a supervised aerobic exercise-training program with specific intensity and energy expenditure goals, compared to a usual activity group. MAIN OUTCOME MEASURES: Time and frequency domain HRV measured at baseline and at 12 weeks for 15min using Holter monitors. RESULTS: Women had a median of 7.6 vasomotor symptoms per 24h. Time and frequency domain HRV measures did not change significantly in either of the intervention groups compared to the change in the usual activity group. HRV results did not differ when the analyses were restricted to post-menopausal women. CONCLUSIONS: Although yoga and exercise have been shown to increase parasympathetic-mediated HRV in other populations, neither intervention increased HRV in middle-aged women with vasomotor symptoms. Mixed results in previous research may be due to sample differences. Yoga and exercise likely improve short-term health in middle-aged women through mechanisms other than HRV. PMID- 27261986 TI - Effectiveness of focused meditation for patients with chronic low back pain-A randomized controlled clinical trial. AB - OBJECTIVES: We aimed to evaluate the effectiveness of an 8-week meditation program (focused meditation) in patients with chronic low-back pain. DESIGN: A randomized clinical trial was conducted on 68 patients (55 years;75% female) with chronic low-back pain who scored >40mm on a 100mm Visual-Analogue-Scale. Subjects were allocated to an 8-week meditation program (focused meditation) with weekly 75min classes or to a self-care exercise program with a wait-list offer for meditation. Both groups were instructed to practice at home. Outcomes were assessed baseline and after 4 and 8 weeks. The primary outcome measure was the change in mean back pain at rest after 8 weeks. Secondary outcomes included function, pain-related bothersomeness, perceived stress, quality-of-life (QOL), and psychological outcomes. RESULTS: Twelve (meditation) and 4 (exercise) patients were lost to follow-up. The primary outcome, pain at rest after 8 weeks, was reduced from 59.3+/-13.9mm to 40.8+/-21.8mm with meditation vs. 52.9+/-11.8mm to 37.3+/-18.2mm with exercise (adjusted group difference: -1.4 (95%CI:11.6;8.8;p=n.s.) Perceived stress was significantly more reduced with meditation (p=0.011). No significant treatment effects were found for other secondary outcomes as pain-related bothersomeness, function, quality-of-life and psychological scores, although the meditation group consistently showed non significant better improvements compared to the exercise group. CONCLUSIONS: Focused meditation and self-care exercise lead to comparable, symptomatic improvements in patients with chronic low back pain. Future studies should include longer-term follow-ups and develop guided meditation programs to support compliance. PMID- 27261987 TI - Mindfulness-based yoga intervention for women with depression. AB - OBJECTIVES: The purpose of this study was to examine the efficacy of a 12-week mindfulness-based yoga intervention on depressive symptoms and rumination among depressed women. DESIGN: Prospective, randomized, controlled 12 week intervention pilot study. Depressive symptoms were assessed at baseline, post-intervention (12 weeks), and one-month follow-up. SETTING: Women with a history of diagnosed depression and currently depressed were randomized to a mindfulness-based yoga condition or a walking control. INTERVENTIONS: The mindfulness-based yoga intervention consisted of a home-based yoga asana, pranayama and meditation practice with mindfulness education sessions delivered over the telephone. The walking control condition consisted of home-based walking sessions and health education sessions delivered over the phone. MAIN OUTCOME MEASURES: The Beck Depression Inventory (BDI) and Ruminative Responses Scale (RRS). RESULTS: Both groups reported decreases in depressive symptoms from baseline to post intervention, f(1,33)=34.83, p<0.001, and from baseline to one-month follow-up, f(1,33)=37.01, p<0.001. After controlling for baseline, there were no significant between group differences on depression scores at post-intervention and the one month follow-up assessment. The mindfulness-based yoga condition reported significantly lower levels of rumination than the control condition at post intervention, after controlling for baseline levels of rumination, f(1,31)=6.23, p<0.01. CONCLUSIONS: These findings suggest that mindfulness-based yoga may provide tools to manage ruminative thoughts among women with elevated depressive symptoms. Future studies, with larger samples are needed to address the effect of yoga on depression and further explore the impact on rumination. PMID- 27261989 TI - A randomized controlled trial of two simple mind-body programs, Kirtan Kriya meditation and music listening, for adults with subjective cognitive decline: Feasibility and acceptability. AB - PURPOSE OF THE STUDY: In this randomized controlled trial (RCT), we assessed the feasibility and acceptability of two simple home-based relaxation programs in adults experiencing subjective cognitive decline, a strong predictor of Alzheimer's disease. DESIGN AND METHODS: Sixty participants were randomized to a beginner Kirtan Kriya meditation (KK) program or a music listening (ML) program. Participants were asked to practice 12min daily for the first 12 weeks, then as often as they liked for the following 3 months. Participants underwent assessments at baseline, 12 weeks, and 6 months to evaluate changes in key outcomes. Feasibility and acceptability were evaluated by measuring recruitment and retention rates, assessment visit attendance, practice adherence, and treatment expectancy; exit questionnaires completed at 12 weeks and 6 months provided additional data regarding participant experience with the study, perceived barriers to and facilitators of practice, reasons for drop-out, and views regarding the assigned intervention. RESULTS: Fifty-three participants (88%) completed the 6 month study. Adherence in both groups was excellent, with participants completing 93% (91% KK, 94% ML) of sessions on average in the first 12 weeks, and 71% (68% KK, 74% ML) during the 3 month, practice-optional, follow up period. At week 12, over 80% of participants indicated they were likely to continue practicing following study completion. Responses to both structured and open-ended exit questionnaire items also suggested high satisfaction with both programs. CONCLUSIONS: Findings of this RCT of a beginner meditation practice and a simple ML program suggest that both programs were well accepted and the practices are feasible in adults with early memory loss. PMID- 27261988 TI - Effects of Buddhist walking meditation on glycemic control and vascular function in patients with type 2 diabetes. AB - OBJECTIVE: To investigate and compare the effects of Buddhist walking meditation and traditional walking on glycemic control and vascular function in patients with type 2 diabetes mellitus. METHODS: Twenty three patients with type 2 diabetes (50-75 years) were randomly allocated into traditional walking exercise (WE; n=11) or Buddhism-based walking meditation exercise (WM; n=12). Both groups performed a 12-week exercise program that consisted of walking on the treadmill at exercise intensity of 50-70% maximum heart rate for 30min/session, 3 times/week. In the WM training program, the participants performed walking on the treadmill while concentrated on foot stepping by voiced "Budd" and "Dha" with each foot step that contacted the floor to practice mindfulness while walking. RESULTS: After 12 weeks, maximal oxygen consumption increased and fasting blood glucose level decreased significantly in both groups (p<0.05). Significant decrease in HbA1c and both systolic and diastolic blood pressure were observed only in the WM group. Flow-mediated dilatation increased significantly (p<0.05) in both exercise groups but arterial stiffness was improved only in the WM group. Blood cortisol level was reduced (p<0.05) only in the WM group. CONCLUSION: Buddhist walking meditation exercise produced a multitude of favorable effects, often superior to traditional walking program, in patients with type 2 diabetes. PMID- 27261990 TI - Use of electronic personal health records (PHRs) for complementary and alternative medicine (CAM) disclosure: Implications for integrative health care. AB - OBJECTIVES: To test a hypothesis that patients' use of Internet-based personal health records (PHRs) will be positively related to their disclosure of their CAM use to medical doctors, controlling for covariates' effects (e.g., health, human capital, and demographics), and to examine the factors influencing patients' CAM use disclosures. DESIGN: Cross-sectional survey. METHODS: We analyzed data in a subsample of CAM users who used both the internet and healthcare services (n=1457) from the Health Information National Trends Survey, a nationally representative study of U.S. adults (>=18), by using a multivariate logistic analysis. RESULTS: Among the subsample, 52.7% disclosed their use of CAM to their doctors and 19.3% used PHRs. Both the bivariate (64.1% vs. 35.9%, p<0.01) and multivariate (beta=0.558, SE=0.220, OR=1.75, p<0.05) analyses revealed a positive relationship between PHR use and CAM use disclosure. Other significant factors for CAM use disclosure included being older, being a female, having insurance, and having regular source of care. Particularly, foreign-born adults had significantly lower odds of disclosing their CAM use than U.S.-born adults. CONCLUSIONS: We found that patients' PHR use facilitated their disclosure of CAM use to medical doctors. To ensure integrative healthcare and integrative medicine in the healthcare sector and optimum care for patients, education for CAM users regarding PHR adoption is encouraged. Next-generation PHR designs should consider incorporating domains for CAM data that allow patients to store CAM data and also incorporating 'intelligent' PHRs, whose contents can be converted into the patient's first language. PMID- 27261991 TI - Dancer perceptions of the cognitive, social, emotional, and physical benefits of modern styles of partnered dancing. AB - OBJECTIVE: To study dancers' perceptions of the physical, cognitive, affective, and social benefits of partnered dancing. METHOD: 225 dancers (71% female) were recruited through a community ballroom dance center and completed an online survey designed to measure their perceptions of the physical, cognitive, affective, and social benefits of modern, partnered dance styles (swing, Lindy Hop, and ballroom dancing). Subgroups were formed for analyses. For one set of analyses, groups based on length of dance participation were formed: experienced (dancing for more than 2 years) or novice (dancing for less than a year) dancers. For another set of analyses, groups based on frequency of dance practice were formed: committed (dancing at least one or more times per week) or occasional (dancing two or fewer times per month). RESULTS: The majority of participants reported perceived benefits in physical fitness, cognition, affect, and social functioning. Experienced dancers reported significantly greater self-perceived physical, social, and cognitive benefits than novice dancers. Committed dancers were more likely than occasional dancers to report improvements in physical fitness, U=6942, z=2.38, r=0.16, p<0.05. A Mann-Whitney test indicated that self reported improvements in mood (i.e., feeling less depressed and more happy) were greater for women than for men, U=3945, z=-3.07, r=0.20, p<0.001. Length and frequency of dance participation significantly predicted perceived physical benefits [Chi(2) (1,6)=35.463, p <0.001, R(2)=0.16] and social benefits [Chi(2) (1,6)=15.776, p<0.05, R(2)=0.07], but not cognitive benefits. CONCLUSIONS: Results suggest that participation in partnered dance styles is associated with perceived improvements in physical fitness, cognitive functioning, social functioning, mood, and self-confidence, and that perceived benefits may increase as individuals dance more frequently and over longer periods of time. PMID- 27261992 TI - The relationship between yoga involvement, mindfulness and psychological well being. AB - OBJECTIVES: The aim of this study was to examine how different levels of yoga involvement are related to different parameters of mental health and illness. DESIGN AND SETTING: A total sample of 455 participants (410 females) were investigated by means of an internet survey. 362 yoga practitioners (327 females) rated their degree of yoga involvement on the Yoga Immersion Scale. A control group was comprised of 93 gymnastics practitioners (83 females). MAIN OUTCOME MEASURES: All participants completed the Multidimensional Inventory for Religious/Spiritual Well-Being, the Freiburger Mindfulness Inventory and the Brief Symptom Inventory for psychiatric symptoms. RESULTS: Highly involved yoga practitioners exhibited a significantly increased amount of mindfulness and religious/spiritual well-being (both p<0.01) and lower psychiatric symptoms such as depression (p<0.01) compared to those who were only marginally/moderately yoga involved or who were in the gymnastics control group. CONCLUSIONS: In accordance with the literature, yoga practice might have its biggest impact on mental health when it is part of a practitioner's worldview. Further research focusing on the impact of yoga involvement in clinical groups is encouraged. PMID- 27261993 TI - Hatha Yoga practice decreases menopause symptoms and improves quality of life: A randomized controlled trial. AB - OBJECTIVES: Yoga practice includes a group of specific psychophysical techniques. Although previous studies showed beneficial effects of yoga for health and rehabilitation, improving quality of life, there are few studies on the possible therapeutic application of yoga during the climacteric period. The purpose of this study was to investigate the psychophysiological effects of Hatha Yoga regular practice in post-menopausal women. METHODS: Eighty-eight post-menopausal women volunteered for this 12-week trial. They were randomly assigned to one of three groups: control (no intervention), exercise, and yoga. Questionnaires were applied in order to evaluate climacteric syndrome (Menopause Rating Scale), stress (Lipp Stress Symptom Inventory), quality of life (Brief World Health Organization Quality of Life), depression (Beck Depression Inventory) and anxiety (State/Trait Anxiety Inventories). Physiological changes were evaluated through hormone levels (cortisol, FSH, LH, progesterone and estradiol). RESULTS: At 12 weeks, yoga practitioners showed statistically lower scores for menopausal symptoms, stress levels and depression symptoms, as well as significantly higher scores in quality of life when compared to control and exercise groups. Only control group presented a significant increase in cortisol levels. The yoga and exercise groups showed decreased levels of FSH and LH when compared to control group. CONCLUSIONS: These results suggest that yoga promotes positive psychophysiological changes in post-menopausal women and may be applied as a complementary therapy towards this population. PMID- 27261994 TI - Lemon balm: A promising herbal therapy for patients with borderline hyperlipidemia-A randomized double-blind placebo-controlled clinical trial. AB - OBJECTIVE: Melissa officinalis is a perennial herb from the Lamiaceae family which has shown to have modulating effects on serum lipid profile. The aim of the current study is to explore the effects of M. officinalis supplementation on serum biochemical parameters of patients with borderline hyperlipidemia. METHODS: 58 hyperlipidemic patients were allocated randomly to 2 groups: first group received capsules containing 1000mg M. officinalis leaf powder (MO group), and the second group received placebo capsules (P group) 3 times per day for 2 months. Fasting blood glucose (FBG), HDL, LDL, Triglyceride, Creatinine and liver function enzymes including AST and ALT were evaluated before and after study. RESULTS: The mean of LDL in MO group significantly decreased compared with P group after the supplementation (P=0.02). Although the level of Cholesterol, FBG, HDL, Triglyceride, Creatinine and ALT did not show significant difference between two groups after 2 months (P>=0.05), the level of AST exhibited a significant difference between two groups (P=0.009). CONCLUSIONS: Our findings demonstrated that M. officinalis supplementation as a rich source of antioxidants and bioactive compounds can be effective in remission of LDL and AST levels in patients with borderline hyperlipidemia. PMID- 27261995 TI - Active versus receptive group music therapy for major depressive disorder-A pilot study. AB - OBJECTIVES: To compare the effects of 1) active group music therapy and 2) receptive group music therapy to group counseling in treatment of major depressive disorder (MDD). DESIGN & SETTING: On top of standard care, 14 MDD outpatients were randomly assigned to receive 1) active group music therapy (n=5), 2) receptive group music therapy (n=5), or 3) group counseling (n=4). There were 12 one-hour weekly group sessions in each arm. MAIN OUTCOME MEASURES: Participants were assessed at baseline, 1 month (after 4 sessions), 3 months (end of interventions), and 6 months. Primary outcomes were depressive scores measured by Montgomery-Asberg Depression Rating Scale (MADRS) Thai version. Secondary outcomes were self-rated depression score and quality of life. RESULTS: At 1 month, 3 months, and 6 months, both therapy groups showed statistically non significant reduction in MADRS Thai scores when compared with the control group (group counseling). The reduction was slightly greater in the active group than the receptive group. Although there were trend toward better outcomes on self report depression and quality of life, the differences were not statistically significant. CONCLUSION: Group music therapy, either active or receptive, is an interesting adjunctive treatment option for outpatients with MDD. The receptive group may reach peak therapeutic effect faster, but the active group may have higher peak effect. Group music therapy deserves further comprehensive studies. PMID- 27261996 TI - Adverse effects of homeopathy, what do we know? A systematic review and meta analysis of randomized controlled trials. AB - OBJECTIVES: Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. DESIGN AND SETTING: Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. RESULTS: A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. CONCLUSION: Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine. PMID- 27261997 TI - Nepeta menthoides Boiss. & Buhse freeze-dried aqueous extract versus sertraline in the treatment of major depression: A double blind randomized controlled trial. AB - BACKGROUND: Depression is the most common psychiatric disorder in the world. The conventional medications for depression, however, often have significant side effects. These adverse effects of conventional therapies, have motivated researchers to study alternative options including complementary and traditional treatments for solving the problem. OBJECTIVE: To compare the efficacy of Nepeta menthoides Boiss. & Buhse freeze-dried aqueous extract with sertraline in the treatment of major depression. DESIGN AND SETTING: From April to September of 2015, 72 patients from two psychiatry clinics of Shiraz University of Medical Sciences who met the criteria for major depression based on the structured clinical interview as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, participated in a two-armed double-blind randomized controlled trial. INTERVENTION: Subjects were randomly assigned to receive Nepeta menthoides or sertraline for four weeks. OUTCOME MEASURES: Patients were evaluated in terms of the Beck Depression Inventory-II (BDI-II) total score and common side effects of medications at the base line, the second and fourth weeks, and two weeks following the intervention (i.e. in the sixth week). RESULTS: The mean changes in the Beck Depression Inventory scores in Nepeta menthoides group were significantly higher in terms of the BDI-II scores diminution as compared to that of the control (p<=0.001). Two weeks follow up after intervention showed a lower recurrence rate in the Nepeta menthoides group (p<=0.001). CONCLUSION: Nepeta menthoides may have potential benefits in the control of mood in patients suffering from major depression. Sustention of antidepressant effect and delay in the recurrence of depression could be considered worthwhile using this herb. PMID- 27261998 TI - Efficacy and safety of Ayurvedic herbs in diarrhoea-predominant irritable bowel syndrome: A randomised controlled crossover trial. AB - OBJECTIVE: Herbal medicines have been used widely for the treatment of irritable bowel syndrome (IBS) patients. The aim of this study is to investigate efficacy and safety of an Ayurvedic herbal compound preparation made from: Murraya koenigii (curry), Punica granatum (pomegranate) and Curcuma longa (turmeric), compared to a placebo in patients with diarrhoea predominant IBS. MATERIAL AND METHODS: This trial was conducted as a randomised placebo-controlled crossover trial with randomised sequence of verum and placebo for each patient. Verum and placebo were provided as ground powders and delivered in sealed containers. Patients and outcome assessors were blinded. Patients were advised to ingest the decoction twice daily for 4 weeks. The primary outcome measure was IBS symptom intensity; secondary outcomes included: quality of life, anxiety and depression, compliance and safety. RESULTS: 32 IBS patients were included in the trial (19 females, mean age 50.3+/-11.9years). Eleven people dropped out during the trial resulting in 37 complete verum and 35 complete placebo phases. No group differences were found between verum and placebo for IBS symptom intensity (difference 24.10; 95% CI: -17.12; 65.32, p=0.26). The same was true for secondary outcomes. Compliance was satisfactory to good and the preparation appeared to be safe, but one third of the patients registered at least one minor adverse event that might be related to the study interventions. CONCLUSION: An Ayurvedic herbal preparation made from Murraya koenigii, Punica granatum and Curcuma longa appeared to be no more effective in improving diarrhoea predominant irritable bowel symptoms than placebo. PMID- 27261999 TI - Diagnose and dispense vs. envision and empower-Integrating yang and yin in health care. PMID- 27262000 TI - Integrated Care and the Evolution of the Multidisciplinary Team. AB - The primary care medical home continues to adapt by applying new research to population health approaches to care. With the discovery that life experiences trigger a chain of biologic events linked to chronic illnesses, the role of patient-centered multidisciplinary care teams becomes of paramount importance. Subsequently, mental health professionals are being incorporated into the primary care setting, using their skills in nontraditional models to customize care for each patient. This "integration" of primary care and unique mental health services engenders opportunity for enhanced clinical care, professional workforce development and support, more effective population health initiatives, and informed health care policy. PMID- 27262001 TI - Behavioral Health in Prevention and Chronic Illness Management: Motivational Interviewing. AB - This article reviews the history, methodology, and evidence related to the effective use of motivational interviewing (MI) in the primary care setting. MI has been shown to have a positive effect in promotion and modification of health habits and to increase treatment engagement. MI is also effective when used in conjunction with other treatment modalities, such as educational programs and cognitive behavioral therapy. Practical application of MI can be accomplished in a variety of primary care settings by a wide range of practitioners, incorporates nicely into new health care delivery models, and may improve the patient-provider relationship. PMID- 27262002 TI - Using Cognitive Behavior Therapy and Mindfulness Techniques in the Management of Chronic Pain in Primary Care. AB - Chronic pain and its associated syndrome have become increasingly prevalent in primary care. With the increase in narcotic use and subsequent adverse events, primary care physicians often seek safer alternatives to treating this condition. Prescribing narcotics necessitates using methods to screen for high abuse risk and protect against misuse. With the understanding of how chronic pain is related to mental illnesses such as depression and posttraumatic stress disorder, mindfulness techniques and behavioral therapy can be used to help decrease the dependence on dangerous opioid medications and help patients understand, accept, and cope with their chronic pain. PMID- 27262003 TI - Substance Abuse Screening and Treatment. AB - One of the more prevalent and often undiagnosed problems seen by primary care clinicians is substance misuse. Resulting in increased morbidity and mortality, loss of productivity, and increased health care costs, substance misuse in our society remains a significant public health issue. Primary care physicians are on the front lines of medical care, and as such, are in a distinctive position to recognize potential problems in this area and assist. This article outlines office-based screening approaches and strategies for managing and treating this complex issue confronting primary care. PMID- 27262004 TI - Depression Screening, Diagnosis, and Treatment Across the Lifespan. AB - This article focuses on six basic components of more effective depression care, emphasizing systems of team-based and collaborative care for diagnosis, monitoring, and follow-up. It also emphasizes the principles of stepped care and proactive and timely intensification of treatment, and discusses various augmentation strategies that all primary care providers could more readily employ. PMID- 27262005 TI - Anxiety Disorders in Primary Care. AB - Investigation for a possible anxiety disorder should be considered in patients with multiple or persistent anxiety symptoms or multiple somatic complaints without a clear somatic etiology. The ideal treatment for anxiety disorders is a combination of pharmacologic and behavioral strategies. As primary care health care evolves, it is expected that the management of mental health disorders (including anxiety disorders) will largely occur in the context of collaborative care models in which patients and primary care clinicians are assisted by trained case managers who help facilitate a more comprehensive, holistic treatment plan between primary care and mental health providers. PMID- 27262006 TI - Pearls for Working with People Who Have Personality Disorder Diagnoses. AB - Personality disorders are a group of diagnostic categories applicable when people show personality traits that are so extreme they cause clear difficulties in their lives and relationships. More widespread agreement is found on sorting by three broad categories (odd/eccentric, dramatic/emotional/erratic, and anxious/fearful) than by more specific subtypes. Primary care physicians need to recognize when extreme personality traits are causing difficulties in their relationships with patients and to have a way to approach these difficulties when they arise. This article reviews current thinking on the diagnosis and treatment of personality disorders, focusing especially on dramatic/emotional/erratic disorders, which are those most often problematic in clinical settings. PMID- 27262007 TI - Bipolar Disorder. AB - Bipolar disorder is a chronic mental health disorder that is frequently encountered in primary care. Many patients with depression may actually have bipolar disorder. The management of bipolar disorder requires proper diagnosis and awareness or referral for appropriate pharmacologic therapy. Patients with bipolar disorder require primary care management for comorbidities such as cardiovascular and metabolic disorders. PMID- 27262008 TI - Autism Spectrum/Pervasive Developmental Disorder. AB - Autism spectrum disorder is a complex disorder that is becoming more prevalent. Because of this increased prevalence, primary care providers must become more knowledgeable about the disorder so they can provide appropriate screening, evaluation, and treatment as part of an interdisciplinary team and to serve patients and families within the medical home. PMID- 27262009 TI - Eating Disorders in the Primary Care Setting. AB - Eating disorders are a complex set of illnesses most commonly affecting white adolescent girls and young women. The most common eating disorders seen in the primary care setting are anorexia nervosa, bulimia nervosa, and binge eating disorder. Treatment in the primary care environment ideally involves a physician, therapist, and nutritionist, although complex cases may require psychiatric and other specialist care. Early diagnosis and treatment are associated with improved outcomes, whereas the consequences of untreated eating disorders, particularly anorexia nervosa, can be devastating, including death. PMID- 27262010 TI - Childhood Sexual Abuse: Identification, Screening, and Treatment Recommendations in Primary Care Settings. AB - It is estimated that 8% to 12% of American youths have experienced at least one sexual assault in their lifetime, making childhood sexual abuse (CSA) an important public health problem that is likely to be encountered by primary care providers. Use of screening tools and understanding the principles behind targeted clinical evaluation can aid in identification of CSA victims despite highly variable presentation. The primary care provider must be aware of potential signs and symptoms as well as differential diagnoses in order to identify children who may benefit from further mental health evaluation and intervention. PMID- 27262011 TI - Psychopharmacology in Primary Care Settings. AB - Psychopharmacology requires clinicians to stay current on the latest guidelines and to use dynamic treatment strategies. Psychiatric conditions are prevalent in the primary care population. Choice of treatment with psychopharmacology should be based on controlling the patient's predominant symptoms while taking into consideration patient age, treatment compliance, patient past response to treatments, dosing frequency, patient preference, medication side effects, potential medication interactions, drug precautions/warnings, and cost. Response to therapy, as well as side effects, needs to be evaluated at regular intervals. The goal is to minimize symptoms and return patients to their maximal level of functioning. PMID- 27262012 TI - Psychiatric Emergencies. AB - Psychiatric emergencies are acute disturbances in thought, behavior, mood, or social relationship that require immediate intervention as defined by the patient, family, or social unit to save the patient and/or others from imminent danger. Ensuring the safety of the patient, surrounding persons, and the medical team is the first step of evaluation. Treatment focuses on stabilization of the patient, then on specific symptoms and ultimately the cause of symptoms. There are important legal considerations, particularly regarding involuntary admissions. It is important to debrief with the patient, surrounding family, and the health care team to ensure a continued therapeutic alliance and the emotional health of all involved. PMID- 27262013 TI - Physician Wellness Across the Professional Spectrum. AB - Physician wellness and burnout are areas of increasing exploration. Physicians are more likely than the general population to suffer the effects of burnout and neglect their own wellness; medicine and its training are deeply engrained with the care of others, often to the detriment of self. The effects vary based on the stage of career for medical trainees and physicians. However, strategies exist to screen for and help alleviate the negative effects of burnout and to improve wellness among physicians. This will continue to be an area warranting further exploration despite increasing awareness regarding the health and well-being of physicians. PMID- 27262014 TI - Objectivity and Compassion. PMID- 27262015 TI - Integrating Psychiatric Care into Primary Care Practice. PMID- 27262016 TI - Omission of axillary dissection after a positive sentinel lymph-node: Implications in the multidisciplinary treatment of operable breast cancer. AB - Omission of axillary dissection in women with breast cancer and one or two positive sentinel-node biopsy is a major advancement in the management of this disease. Supported by a sound rationale and confirmed by prospective, randomized trials, omission of axillary dissection is now recommended in women who have undergone breast conserving surgery and who are candidate to adjuvant radiotherapy. Because breast cancer is best managed in the context of a multidisciplinary team, this surgical shift in the paradigm is expected to have implications that extend also to the other specialties involved in the team. In fact, the full evaluation of the axillary tumor burden has been historically considered an essential part of tumor staging and the absolute number of involved node critical information to tailor post-surgical treatments. Lack of this information in a patient with axillary involvement documented by a positive sentinel lymph-node biopsy may represent a challenge when deciding on further, post-surgical treatments. This review will address the critical aspects and the potential implications of omission of axillary dissection in the context of the multidisciplinary breast team. PMID- 27262017 TI - Can the response to a platinum-based therapy be predicted by the DNA repair status in non-small cell lung cancer? AB - Preclinical evidence has been accumulating on the impact of the DNA repair status on the sensitivity/resistance to anticancer agents in different tumor types, including lung cancer. The possibility to predict the response to therapy, and specifically to platinum agents, based on tumor specific DNA repair functionality would enable to tailor its use only in those patients with maximum chances to respond, avoiding the burden of toxicity in those ones with lesser chances. We here reviewed the clinical evidence on the prognostic role of DNA repair markers and/or functional assays in predicting the response to a platinum-based chemotherapy in lung cancer patients. Consequently, we focused on those proteins involved in pathways repairing platinum induced DNA inter-strand and intra-strand crosslinks. Most promising clinical trials targeting the nucleotide repair protein ERCC1 in non-small cell lung cancer later on suffered from serious drawbacks. Nevertheless, these results spurred a variety of preclinical studies on a multitude of alternative DNA repair markers. However so far, no one of the analyzed DNA repair markers can be considered a reliable and mature biomarker for selecting patients. We discuss the reasons for such failure which discloses novel strategies for the future. PMID- 27262018 TI - Perivascular administration: The outside-in concept. PMID- 27262019 TI - Tumor targeting of gene expression through metal-coordinated conjugation with dextran [J. Control. Release (2003) 88 297-312]. PMID- 27262020 TI - Enhanced expression of plasmid dna - cationized gelatin complex by ultrasound in murine muscle [J. Control. Release 80 (2002) 345-356]. PMID- 27262021 TI - Retraction notice to "In vitro gene expression by cationized derivatives of an artificial protein with repeated RGD sequences, pronectin(r)" [J. Control. Release 86 (2002) 169-182]. PMID- 27262022 TI - Retraction notice to "Ultrasound enhances in vivo tumor expression of plasmid DNA by PEG-introduced cationized dextran" [J. Control. Release 108 (2005) 540-556]. PMID- 27262023 TI - Retraction notice to "PEGylation enhances tumor targeting of plasmid DNA by an artificial cationized protein with repeated RGD sequences, Pronectin(r)" [J. Control. Release 97 (2004) 157-171]. PMID- 27262024 TI - "Bone regeneration through controlled release of bone morphogenetic protein-2 from 3-D tissue engineered nano-scaffold" [J. Control. Release 117 (2006) 380 386]. PMID- 27262025 TI - Generation of HLA-Universal iPSC-Derived Megakaryocytes and Platelets for Survival Under Refractoriness Conditions. AB - Platelet (PLT) transfusion is indispensable to maintain homeostasis in thrombocytopenic patients. However, PLT transfusion refractoriness is a common life-threatening condition observed in multitransfused patients. The most frequent immune cause for PLT transfusion refractoriness is the presence of alloantibodies specific for human leukocyte antigen (HLA) class I epitopes. Here, we have silenced the expression of HLA class I to generate a stable HLA-universal induced pluripotent stem cell (iPSC) line that can be used as a renewable cell source for the generation of low immunogenic cell products. The expression of HLA class I was silenced by up to 82% and remained stable during iPSC cultivation. In this study, we have focused on the generation of megakaryocytes (MK) and PLTs from a HLA-universal iPSC source under feeder- and xeno-free conditions. On d 19, differentiation rates of MKs and PLTs with means of 58% and 76% were observed, respectively. HLA-universal iPSC-derived MKs showed polyploidy with DNA contents higher than 4n and formed proPLTs. Importantly, differentiated MKs remained silenced for HLA class I expression. HLA-universal MKs produced functional PLTs. Notably, iPSC-derived HLA-universal MKs were capable to escape antibody-mediated complement- and cellular-dependent cytotoxicity. Furthermore, HLA-universal MKs were able to produce PLTs after in vivo transfusion in a mouse model indicating that they might be used as an alternative to PLT transfusion. Thus, in vitro produced low immunogenic MKs and PLTs may become an alternative to PLT donation in PLT-based therapies and an important component in the management of severe alloimmunized patients. PMID- 27262026 TI - Plasma Fibrinogen Is a Natural Deterrent to Amyloid Beta-Induced Platelet Activation. AB - Alzheimer's disease (AD) is a devastating neurodegenerative disorder, characterized by extensive loss of neurons, and deposition of amyloid beta (Abeta) in the form of extracellular plaques. Abeta is considered to have critical role in synaptic loss and neuronal death underlying cognitive decline. Platelets contribute to 95% of circulating amyloid-precursor protein that releases Abeta into circulation. We have recently demonstrated that, Abeta active fragment containing amino acid sequence 25-35 (Abeta25-35) is highly thrombogenic in nature, and elicits strong aggregation of washed human platelets in RhoA dependent manner. In the present study we evaluated the influence of fibrinogen on Abeta-induced platelet activation. Intriguingly, Abeta failed to induce aggregation of platelets suspended in plasma but not in buffer. Fibrinogen brought about dose-dependent decline in aggregatory response of washed human platelets elicited by Abeta25-35, which could be reversed by increasing doses of Abeta. Fibrinogen also attenuated Abeta-induced platelet responses like secretion, clot retraction, rise in cytosolic Ca+2 and reactive oxygen species (ROS). Fibrinogen prevented intracellular accumulation of full length amyloid beta peptide (Abeta42) in platelets as well as neuronal cells. We conclude that fibrinogen serves as a physiological check against the adverse effects of Abeta by preventing its interaction with cells. PMID- 27262027 TI - Smart hyaluronidase-actived theranostic micelles for dual-modal imaging guided photodynamic therapy. AB - We here report smart hyaluronidase-actived theranostic nanoparticles based on hyaluronic acid (HA) coupled with chlorin e6 (Ce6) via adipic dihydrazide (ADH) forming HA-ADH-Ce6 conjugates and self-assembling into HACE NPs. The resulting nanoparticles showed stable nano-structure in aqueous condition with uniform size distribution and can be actively disassembled in the presence of hyaluronidase (over-expressed in tumor cells), exhibiting hyaluronidase-responsive "OFF/ON" behavior of fluorescence signal. The HACE NPs were rapidly taken up to human lung cancer cells A549 via CD44 (the HA receptor on the surface of tumor cells) receptor mediated endocytosis. Upon laser irradiation, the HACE NPs realized good near-infrared fluorescence imaging and photoacoustic imaging in the tumor bearing mice, which showed 5-fold higher fluorescence intensity and 3-fold higher photoacoustic (PA) intensity than free Ce6, respectively. In addition, under low dose of laser power, the HACE NPs presented more effective photodynamic therapy to suppression of tumor growth than free Ce6 in vitro and in vivo. Overall, these results suggest that the well-defined HACE NPs is a biocompatible theranostic nanoplatform for in vivo dual-modal tumor imaging and phototherapy simultaneously. PMID- 27262028 TI - Differential expression of postsynaptic NMDA and AMPA receptor subunits in the hippocampus and prefrontal cortex of the flinders sensitive line rat model of depression. AB - Glutamatergic abnormalities have recently been implicated in the pathophysiology of depression, and the ionotropic glutamate receptors in particular have been suggested as possible underlying molecular determinants. The Flinders Sensitive Line (FSL) rats constitute a validated model of depression with dysfunctional regulation of glutamate transmission relatively to their control strain Flinders Resistant Line (FRL). To gain insight into how signaling through glutamate receptors may be altered in the FSL rats, we investigated the expression and phosphorylation of AMPA and NMDA receptor subunits in an enriched postsynaptic fraction of the hippocampus and prefrontal cortex. Compared to the hippocampal postsynaptic fractions of FRL rats, FSL rats exhibited decreased and increased levels of the NMDA receptor subunits GluN2A and GluN2B, respectively, causing a lower ratio of GluN2A/GluN2B. The GluA2/GluA3 AMPA receptor subunit ratio was significantly decreased while the expression of the individual GluA1, GluA2, and GluA3 subunits were unaltered including phosphorylation levels of GluA1 at S831 and S845. There were no changes in the prefrontal cortex. These results support altered expression of postsynaptic glutamate receptors in the hippocampus of FSL rats, which may contribute to the depressive-like phenotype of these rats. PMID- 27262029 TI - Depth-dependent plasticity in opsin gene expression varies between damselfish (Pomacentridae) species. AB - Phenotypic plasticity plays an important role in adapting the visual capability of many animal species to changing sensory requirements. Such variability may be driven by developmental change or may result from environmental changes in light habitat, thereby improving performance in different photic environments. In this study, we examined inter- and intraspecific plasticity of visual sensitivities in seven damselfish species, part of the species-rich and colourful fish fauna of the Great Barrier Reef in Australia. Our goal was to test whether the visual systems of damselfish were tuned to the prevailing light environment in different habitats and/or other aspects of their lifestyle. More specifically, we compared the opsin gene expression levels from individuals living in different photic habitats. We found that all species expressed rod opsin (RH1) used for dim-light vision, and primarily three cone opsins (SWS1, RH2B and RH2A) used for colour vision. While RH1 levels changed exclusively following a diurnal cycle, cone opsin expression varied with depth in four of the seven species. Estimates of visual pigment performance imply that changes in opsin expression adjust visual sensitivities to the dominant photic regime. However, we also discovered that some species show a more stable opsin expression profile. Further, we found indication that seasonal changes, possibly linked to changes in the photic environment, might also trigger opsin expression. These findings suggest that plasticity in opsin gene expression of damselfish is highly species-specific, possibly due to ecological differences in visual tasks or, alternatively, under phylogenetic constraints. PMID- 27262030 TI - Multiple cryptic species of sympatric generalists within the avian blood parasite Haemoproteus majoris. AB - The avian haemosporidian parasite Haemoproteus majoris has been reported to infect a wide range of passerine birds throughout the Holarctic ecozone. Five cytochrome b (cyt b) lineages have been described as belonging to the morphological species H. majoris, and these form a tight phylogenetic cluster together with 13 undescribed lineages that differ from each other by < 1.2% in sequence divergence. Records in a database (MalAvi) that contains global findings of haemosporidian lineages generated by universal primers suggest that these lineages vary substantially in host distribution. We confirm this pattern in a data set collected at Lake Kvismaren, Sweden, where three of the generalist lineages have local transmission. However, whether these lineages represent intraspecific mitochondrial diversity or clusters of cryptic species has previously not been examined. In this study, we developed novel molecular markers to amplify the partial segments of four nuclear genes to determine the level of genetic diversity and gene phylogenies among the five morphologically described cyt b lineages of H. majoris. All five cyt b lineages were strongly associated with unique nuclear alleles at all four nuclear loci, indicating that each mitochondrial lineage represents a distinct biological species. Within lineages, there was no apparent association between nuclear alleles and host species, indicating that they form genetically unstructured populations across multiple host species. PMID- 27262031 TI - Optimal conservation resource allocation under variable economic and ecological time discounting rates in boreal forest. AB - Resource allocation to multiple alternative conservation actions is a complex task. A common trade-off occurs between protection of smaller, expensive, high quality areas versus larger, cheaper, partially degraded areas. We investigate optimal allocation into three actions in boreal forest: current standard forest management rules, setting aside of mature stands, or setting aside of clear-cuts. We first estimated how habitat availability for focal indicator species and economic returns from timber harvesting develop through time as a function of forest type and action chosen. We then developed an optimal resource allocation by accounting for budget size and habitat availability of indicator species in different forest types. We also accounted for the perspective adopted towards sustainability, modeled via temporal preference and economic and ecological time discounting. Controversially, we found that in boreal forest set-aside followed by protection of clear-cuts can become a winning cost-effective strategy when accounting for habitat requirements of multiple species, long planning horizon, and limited budget. It is particularly effective when adopting a long-term sustainability perspective, and accounting for present revenues from timber harvesting. The present analysis assesses the cost-effective conditions to allocate resources into an inexpensive conservation strategy that nevertheless has potential to produce high ecological values in the future. PMID- 27262032 TI - Assessing the relation of USDA conservation expenditures to suspended sediment reductions in an Iowa watershed. AB - From 1936 to 2010, U.S. Department of Agriculture (USDA) agencies spent $293.7 billion (value adjusted for inflation at the 2009 level) on conservation programs. Of these expenditures, $75.2 billion (26%) were allocated for technical assistance (TA; it is related to costs associated with USDA field staff providing their expert advice to farmers) and $218.5 billion (74%) for financial assistance (FA; monetary incentives for farmers to adopt conservation programs). A major environmental goal of these programs was to reduce soil erosion and sediment leaving the land. In this study, we correlate expenditures on FA and TA programs to a unique long (1937-2009) record of total suspended solids (TSS) and sediment load (SL) for the Raccoon River at Van Meter, Iowa. Study results suggest that three predictors (rainfall, TA and FA) are important in explaining the temporal changes in annual TSS and SL and provide evidence that USDA expenditures helped reduce TSS and SL in the Raccoon River. TA was more effective than FA in reducing TSS levels in the watershed. Our empirical model represents an initial, broad scale attempt to correlate conservation expenditures to a specific water quality outcome, although more work is needed to disentangle the impacts associated with other unexplored factors. PMID- 27262033 TI - Optimization of operating parameters of hybrid vertical down-flow constructed wetland systems for domestic sewerage treatment. AB - In this work, three hybrid vertical down-flow constructed wetland (HVDF-CW) systems with different compound substrates were fed with domestic sewage and their pollutants removal performance under different hydraulic loading and step feeding ratio was investigated. The results showed that the hydraulic loading and step-feeding ratio were two crucial factors determining the removal efficiency of most pollutants, while substrate types only significantly affected the removal of COD and NH4(+)-N. Generally, the lower the hydraulic loading, the better removal efficiency of all contaminants, except for TN. By contrast, the increase of step feeding ratio would slightly reduce the removal rate of ammonium and TP but obviously promoted the TN removal. Therefore, the optimal operation of this CWs could be achieved with low hydraulic loading combined with 50% of step-feeding ratio when TN removal is the priority, whereas medium or low hydraulic loading without step-feeding would be suitable when TN removal is not taken into consideration. The obtained results in this study can provide us with a guideline for design and optimization of hybrid vertical flow constructed wetland systems to improve the pollutants removal from domestic sewage. PMID- 27262034 TI - Electricity generation through degradation of organic matters in medicinal herbs wastewater using bio-electro-Fenton system. AB - In the present study, the potential application of the bio-electro-Fenton (BEF) process for the treatment of medicinal herbs wastewater in a mediator-less microbial fuel cell (MFC) system is investigated. This process is operated in a dual-chamber MFC with anaerobic seed sludge as biocatalyst in an anode chamber under conditions of neutral pH, an aerobic cathode chamber equipped with a Fe@Fe2O3/graphite composite cathode and a Nafion membrane as a separator. The performance of the MFC is determined in three different mixed liquor suspended solids (MLSS) loadings, Nafions (112, 115) and a salt bridge in an air-cathode BEF process, in terms of power generation, chemical oxygen demand (COD) removal efficiency, columbic and energy efficiencies. Under optimal conditions, the batch experiment results show that the cathode chamber of the BEF reactor, equipped with Nafion 112 and inoculated with seed sludge at 3000 mg L(-1) MLSS concentration, produces the maximum power density of 49.76 mW m(-2), 0.56 mg L( 1) and 29 mol L(-1) of H2O2 and Fe(2+), respectively. Under these conditions, the MFC achieves COD removal 78.05% in the anaerobic anode chamber and 84.02% as a result of aerobic processes from the air-cathode BEF chamber, whilst the maximum voltage epsiloncb and epsilonE values are 600 mV, 4.09% and 1.37%, respectively. PMID- 27262035 TI - Reply. PMID- 27262036 TI - Naming names. PMID- 27262037 TI - Zeroing in on violent recidivism among released prisoners. PMID- 27262038 TI - A global mental health fund for serious mental illness in low-income and middle income countries. PMID- 27262039 TI - When can neurofeedback join the clinical armamentarium? PMID- 27262041 TI - Corrections. PMID- 27262040 TI - Corrections. PMID- 27262042 TI - Selection of cognitive tests for trials of therapeutic agents. PMID- 27262043 TI - Selection of cognitive tests for trials of therapeutic agents - Authors' reply. PMID- 27262044 TI - Homelessness and mental health in India. PMID- 27262045 TI - Violence against nurses in China undermines task-shifting implementation. PMID- 27262046 TI - NICE guidance: why not clozapine for treatment-refractory bipolar disorder? PMID- 27262047 TI - The birth of a psychiatric orphan disorder: postpartum psychosis. PMID- 27262048 TI - NICE guidance: why not clozapine for treatment-refractory bipolar disorder? - Authors' reply. PMID- 27262050 TI - Flavio Kapczinski. PMID- 27262051 TI - A rabbit model of cerebral microembolic signals for translational research: preclinical validation for aspirin and clopidogrel. AB - Essentials Microembolic signal (MES) is an independent predictor of stroke risk in patients. A rabbit model of cerebral microembolic signals was established. Therapeutic efficacy was demonstrated for aspirin and clopidogrel on microembolic signals. Potential translational value of this preclinical model of MES was demonstrated. SUMMARY: Objectives Cerebral microembolic signals (MESs) detected by transcranial Doppler (TCD) ultrasound constitute an independent predictor of stroke risk and prognosis. The aim of this study was to develop a novel preclinical model of MESs to facilitate translational research. Methods A clinical TCD ultrasound machine was used to detect MESs in the cerebral circulation of New Zealand White rabbits. Technical feasibility was assessed for the measurement of MESs in the middle cerebral artery (MCA) by TCD. FeCl3 induced carotid arterial thrombosis was optimized for the generation of endogenous microemboli. Ascending doses of two antithrombotic agents (aspirin and clopidogrel) were evaluated individually and in combination for their effects on both arterial thrombosis and MESs in a 30% FeCl3 -induced carotid arterial thrombosis model, along with ex vivo functional assays. Results Dose-dependent FeCl3 -induced arterial thrombosis studies showed that 30% FeCl3 resulted in the most consistent and reproducible MESs in the MCA (3.3 +/- 0.7 MESs h(-1) ). Ascending-dose studies showed that the effective doses for 50% inhibition (ED50 ) of thrombus formation, based on integrated blood flow and thrombus weight, respectively, were 3.1 mg kg(-1) and 4.2 mg kg(-1) orally for aspirin, and 0.3 mg kg(-1) and 0.28 mg kg(-1) orally for clopidogrel. The ED50 values for MES incidence were 12.7 mg kg(-1) orally for aspirin, and 0.25 mg kg(-1) orally for clopidogrel. Dual treatment with aspirin (5 mg kg(-1) ) and clopidogel (0.3 mg kg(-1) ) resulted in significant reductions in cerebral MESs (P < 0.05) as compared with monotherapy with either agent. Conclusions Our study demonstrated the successful establishment of the MES model in rabbits, and it may provide translational value for MESs and ischemic stroke research. PMID- 27262052 TI - Destruction-and-diffraction by X-ray free-electron laser. AB - It is common knowledge that macromolecular crystals are damaged by the X-rays they are exposed to during conventional data collection. One of the claims made about the crystallographic data collection now being collected using X-ray free electron lasers (XFEL) is that they are unaffected by radiation damage. XFEL data sets are assembled by merging data obtained from a very large number of crystals, each of which is exposed to a single femtosecond pulse of radiation, the duration of which is so short that diffraction occurs before the damage done to the crystal has time to become manifest, i.e. "diffraction-before-destruction." However, recent theoretical studies have shown that many of the elemental electronic processes that ultimately result in the destruction of such crystals occur during a single pulse. It is predicted that the amplitudes of atomic scattering factor could be reduced by as much as 75% within the first 5 femtoseconds of such pulses, and that different atoms will respond in different ways. Experimental evidence is provided here that these predictions are correct. PMID- 27262054 TI - Radiation Dose Management: Are We Doing Enough to Ensure Adoption of Best Practices? PMID- 27262053 TI - Characterization of the cyanobacteria and associated bacterial community from an ephemeral wetland in New Zealand. AB - New Zealand ephemeral wetlands are ecologically important, containing up to 12% of threatened native plant species and frequently exhibiting conspicuous cyanobacterial growth. In such environments, cyanobacteria and associated heterotrophs can influence primary production and nutrient cycling. Wetland communities, including bacteria, can be altered by increased nitrate and phosphate due to agricultural practices. We have characterized cyanobacteria from the Wairepo Kettleholes Conservation Area and their associated bacteria. Use of 16S rRNA amplicon sequencing identified several operational taxonomic units (OTUs) representing filamentous heterocystous and non-heterocystous cyanobacterial taxa. One Nostoc OTU that formed macroscopic colonies dominated the cyanobacterial community. A diverse bacterial community was associated with the Nostoc colonies, including a core microbiome of 39 OTUs. Identity of the core microbiome associated with macroscopic Nostoc colonies was not changed by the addition of nutrients. One OTU was highly represented in all Nostoc colonies (27.6%-42.6% of reads) and phylogenetic analyses identified this OTU as belonging to the genus Sphingomonas. Scanning electron microscopy showed the absence of heterotrophic bacteria within the Nostoc colony but revealed a diverse community associated with the colonies on the external surface. PMID- 27262055 TI - Strange Bedfellows. PMID- 27262057 TI - The Nationwide Evaluation of X-Ray Trends, Part I: More Than 40 Years of Surveying the US Radiology Practice. PMID- 27262058 TI - Deal or No Deal? Negotiation 101. PMID- 27262059 TI - Erratum. PMID- 27262056 TI - ACR Appropriateness Criteria Head Trauma. AB - Neuroimaging plays an important role in the management of head trauma. Several guidelines have been published for identifying which patients can avoid neuroimaging. Noncontrast head CT is the most appropriate initial examination in patients with minor or mild acute closed head injury who require neuroimaging as well as patients with moderate to severe acute closed head injury. In short-term follow-up neuroimaging of acute traumatic brain injury, CT and MRI may have complementary roles. In subacute to chronic traumatic brain injury, MRI is the most appropriate initial examination, though CT may have a complementary role in select circumstances. Advanced neuroimaging techniques are areas of active research but are not considered routine clinical practice at this time. In suspected intracranial vascular injury, CT angiography or venography or MR angiography or venography is the most appropriate imaging study. In suspected posttraumatic cerebrospinal fluid leak, high-resolution noncontrast skull base CT is the most appropriate initial imaging study to identify the source, with cisternography reserved for problem solving. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 27262061 TI - Pitfalls and optimal approaches to diagnose melioidosis. AB - Melioidosis is a severe and fatal infectious disease in the tropics and subtropics. It presents as a febrile illness with protean manifestation ranging from chronic localized infection to acute fulminant septicemia with dissemination of infection to multiple organs characterized by abscesses. Pneumonia is the most common clinical presentation. Because of the wide range of clinical presentations, physicians may often misdiagnose and mistreat the disease for tuberculosis, pneumonia or other pyogenic infections. The purpose of this paper is to present common pitfalls in diagnosis and provide optimal approaches to enable early diagnosis and prompt treatment of melioidosis. Melioidosis may occur beyond the boundaries of endemic areas. There is no pathognomonic feature specific to a diagnosis of melioidosis. In endemic areas, physicians need to expand the diagnostic work-up to include melioidosis when confronted with clinical scenarios of pyrexia of unknown origin, progressive pneumonia or sepsis. Radiological imaging is an integral part of the diagnostic workup. Knowledge of the modes of transmission and risk factors will add support in clinically suspected cases to initiate therapy. In situations of clinically highly probable or possible cases where laboratory bacteriological confirmation is not possible, applying evidence-based criteria and empirical treatment with antimicrobials is recommended. It is of prime importance that patients undergo the full course of antimicrobial therapy to avoid relapse and recurrence. Early diagnosis and appropriate management is crucial in reducing serious complications leading to high mortality, and in preventing recurrences of the disease. Thus, there is a crucial need for promoting awareness among physicians at all levels and for improved diagnostic microbiology services. Further, the need for making the disease notifiable and/or initiating melioidosis registries in endemic countries appears to be compelling. PMID- 27262060 TI - Revisiting the mechanisms of copper toxicity to rainbow trout: Time course, influence of calcium, unidirectional Na(+) fluxes, and branchial Na(+), K(+) ATPase and V-type H(+) ATPase activities. AB - In order to resolve uncertainties as to the mechanisms of toxic action of Cu and the protective effects of water [Ca], juvenile rainbow trout were acclimated to baseline soft water (SW, [Na(+)]=0.07, [Ca(2+)]=0.15, [Mg(2+)]=0.05mmolL(-1)) and then exposed to Cu with or without elevated [Ca] but at constant titratable alkalinity (0.27mmolL(-1)). The 96-h LC50 was 7-fold higher (63.8 versus 9.2MUgCuL(-1); 1.00 versus 0.14MUmolCuL(-1)) at [Ca]=3.0 versus 0.15mmolL(-1). Gill Cu burden increased with exposure concentration, and higher [Ca] attenuated this accumulation. At 24h, the gill Cu load (LA50~0.58MUgCug(-1); 9.13nmolCug( 1)) predictive of 50% mortality by 96h was independent of [Ca], in accord with Biotic Ligand Model (BLM) theory. Cu exposure induced net Na(+) losses (J(Na)net) by increasing unidirectional Na(+) efflux rates (J(Na)out) and inhibiting unidirectional Na(+) uptake rates (J(Na)in). The effect on J(Na)out was virtually immediate, whereas the effect on J(Na)in developed progressively over 24h and was associated with an inhibition of branchial Na(+), K(+) ATPase activity. The J(Na)in inhibition was eventually significant at a lower Cu threshold concentration (15MUgCuL(-1)) than the J(Na)out stimulation (100MUg Cu L(-1)). Elevated Ca protected against both effects, as well as against the inhibition of Na(+), K(+) ATPase activity. Branchial V-type H(+) ATPase activity was also inhibited by Cu exposure (100MUgCuL(-1)), but only after 24h at high [Ca] (3.0mmolL(-1)). These novel results therefore reinforce the applicability of BLM theory to Cu, clarify that whether Na(+) influx or efflux is more sensitive depends on the duration of Cu exposure, show that elevated water [Ca], independent of alkalinity, is protective against both mechanisms of Cu toxicity, and identify V-type H(+)ATPase as a new Cu target for future investigation. PMID- 27262062 TI - Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target. AB - Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria. PMID- 27262063 TI - Methanol extract of Codium fragile inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-kappaB activation. AB - OBJECTIVE: To evaluate whether the methanol extract of Codium fragile (MECF) regulates tumor necrosis factor-alpha (TNF-alpha)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9 (MMP-9). METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-kappaB (NF-kappaB) subunits, p65 and p50, and IkappaB in MDA-MB-231 cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used for cell viability. MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay, respectively. NF-kappaB activity was measured by an electrophoretic mobility shift assay and luciferase activity. RESULTS: MECF had no effect on cell viability up to a concentration of 100 MUg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-alpha. MDA-MB-231 cells that were stimulated with TNF-alpha showed a marked increase of invasion compared to the untreated control, whereas pretreatment with MECF downregulated the TNF-alpha-induced invasion of MDA-MB-231 cells. Additionally, zymography, western blot analysis, and RT-PCR confirmed that MECF decreased TNF alpha-induced MMP-9 expression and activity which is a key regulator for cancer invasion. According to an electrophoretic morbidity shift assay, pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-alpha-induced DNA binding activity of NF-kappaB, which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9. Furthermore, treatment with MECF sustained the expression of p65 and p50 in response to TNF-alpha in the cytosolic compartment. The luciferase assay demonstrated that MECF attenuated TNF alpha-induced NF-kappaB luciferase activity. CONCLUSION: MECF exhibited its anti invasive capability by downregulating TNF-alpha-induced MMP-9 expression, resulting from the suppression of NF-kappaB activity in the human breast cancer cell line MDA-MB-231. PMID- 27262064 TI - The inhibition effect of Chlorpromazine against the beta-lactam resistance of MRSA. AB - OBJECTIVE: To investigate the gene related to beta-lactam resistance and to confirm the mechanism about a synergy effect between CPZ and beta-lactam antibiotics. METHODS: To measure antibacterial activity, we performed a minimum inhibitory concentration (MIC) and synergy test. Transmission electron microscopy (TEM) was used in morphological analysis. To analyze gene expression, we conducted reverse transcriptase polymerase chain reaction (PCR). RESULTS: We confirmed a synergy effect between CPZ and beta-lactam antibiotics. Furthermore, we observed that CPZ affect the cell envelope of MRSA by using TEM. At the gene level, CPZ reduced the expression of resistance genes. CONCLUSIONS: Through this result, we hypothesize that a decrease of resistance factor expressions was caused by CPZ because it disrupts the activity of a sensor protein located in the cell membrane. PMID- 27262065 TI - Nevirapine induces apoptosis in liver (HepG2) cells. AB - OBJECTIVE: To generate insights into the mechanism of NVP induced hepatotoxicity. METHODS: Liver (HepG2) cells were cultured with various concentrations of NVP. This cell line was chosen because it has low expression of cytochrome P450, allowing evaluation of the effects of NVP rather than specific metabolites. Cytotoxicity was determined using a proliferation assay and cell numbers were monitored using trypan blue exclusion assay for long term culture experiments and apoptosis induction was determined by morphological and biochemical investigation. RESULTS: HepG2 cells treated with the highest concentration of NVP tested (819 MUM) initially showed a rounded morphology and all cells had died by week three of exposure. Nuclear condensation and fragmentation, increased Annexin V/propidium iodide staining and caspase 9 activation all supported the induction of apoptosis in HepG2 cells in response to NVP treatment. CONCLUSIONS: There is a clear induction of apoptosis in response to NVP which suggests that NVP has significant cytotoxicity, over and above any cytotoxicity of metabolites and may contribute directly to patient hepatotoxicity. PMID- 27262066 TI - Chemical constituents, cytotoxic, antifungal and antimicrobial properties of Centaurea diluta Ait. subsp. algeriensis (Coss. & Dur.) Maire. AB - OBJECTIVE: To investigate the chemical composition of a moderately polar extract (CHCl3 soluble part of the MeOH-H2O extract) obtained from the aerial parts (leaves and flowers) of Centaurea diluta Ait. subsp. algeriensis (Coss. & Dur.) Maire, a species endemic to Algeria and Morocco on which no reports are available to date. To evaluate in vitro the cytotoxic, antifungal and antimicrobial activities of this extract and the cytotoxic and antimicrobial activities of its isolated secondary metabolites. METHODS: The cytotoxic effects of the extract were investigated on 3 human cancer cell lines i.e. the A549 non-small-cell lung carcinoma (NSCLC), the MCF7 breast adenocarcinoma and the U373 glioblastoma using a MTT colorimetric assay. Biological data allowed to guide the fractionation of the extract by separation and purification on silica gel 60 (CC and TLC). The isolated compounds which were characterized by spectral analysis, mainly HR ESIMS, HR-EIMS, UV and NMR experiments ((1)H, (13)C, COSY, ROESY, HSQC and HMBC) and comparison of their spectroscopic data with those reported in the literature, were evaluated for cytotoxic activities on six cancer cell lines (A549, MCF7, U373, Hs683 human glioma, PC3 human prostate and B16-F10 murine melanoma). The direct and indirect antibacterial and antifungal activities were determined using microdilution methods for the raw extract and TLC-bioautography and microdilution methods against standard and clinical strains for the isolated compounds. RESULTS: The raw extract reduced cell viability with IC50s of 27, 25 and 21 MUg/mL on A549, MCF7 and U373, respectively. Five secondary metabolites: two phenolic compounds (vanillin 1, paridol 3), a lignan [(-)-arctigenin 2] and two flavonoid aglycones (eupatilin 4 and jaceosidin 5), were then isolated from this extract. Moderate cytotoxic effects were observed for (-)-arctigenin 2 (IC50s: 28 and 33 MUM on Hs683 and B16-F10, respectively), eupatilin 4 (IC50s: 33 and 47 MUM on B16-F10 and PC3, respectively) and jaceosidin 5 (IC50s: 32 and 40 MUM on PC3 and B16-F10, respectively). CONCLUSIONS: All the isolated compounds were described for the first time from this species. Although inactive against 7 tested microorganisms (fungi, bacteria and yeast, human or plant pathogens), the raw extract was able to potentiate the effect of beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus (MRSA), reducing the minimal inhibitory concentrations (MICs) by a factor of 2-32-fold. No synergy was found between the extract and streptomycin. From the five isolated compounds only jaseosidin 5 showed a moderate antimicrobial activity. PMID- 27262067 TI - Oyster is an effective transmission vehicle for Cryptosporidium infection in human. AB - OBJECTIVE: To determine the ability of oysters to trap and maintain viable Cryptosporidium oocysts, and the feasibility of Cryptosporidium multiplication in oysters' organs. METHODS: Seventy oysters were raised in experimentally seeded natural seawater for up to 3 months, with weekly oocysts inoculations. Cryptosporidium oocysts, viable and non-viable, as well as other stages were detected using two immunofluorescence vital staining techniques (Sporo-Glo and Merifluor((r))) with confocal microscopy. Viability rate at various times after inoculations were calculated. RESULTS: Cryptosporidium oocysts were found most concentrated in oysters' digestive organs than in gill and water inside the oysters. Oocysts numbers were 857.33 at 24 h after inoculation and strikingly decreased to 243.00 and 126.67 oocysts at 72 h and 7 days, respectively. The oocysts in oyster were also less viable over time; 70%, 60% and 30% viable at 24 h, 72 h and 7 days after inoculation, respectively. At 77 days, the number of oocysts was very low and none was found at 84 days onwards. Although some oocysts were ruptured with released sporozoites, there was no evidence throughout the study of sporozoites multiplication to indicate that oyster is a biological host. Despite the significant reduction in oocysts number after 7 days of inoculation, the remained viable oocysts can still cause cryptosporidiosis. CONCLUSION: The findings confirm that Cryptosporidium parvum does not multiply in oyster, and is therefore not a biological host. Nevertheless, the results suggest that oyster can be an effective transmission vehicle for Cryptosporidium oocysts, especially within 24-72 h of contamination, with viable oocysts present at up to 7 days post infection. Unless consuming well-cooked oyster dishes, eating raw oyster remains a public health concern and at least 3 days of depuration in clean sea water prior to consumption is recommended. PMID- 27262068 TI - Effect of hypoxia on expression of placental trophoblast cells SATB1 and beta catenin and its correlation with the pathogenesis of preeclampsia. AB - OBJECTIVE: To study the effect of hypoxia on the expression of placental trophoblast cells SATB1 and beta-catenin and its correlation with the pathogenesis of preeclampsia. METHODS: Trophoblastic cell lines HRT8/SVneo were cultured, SATB1 and beta-catenin expression and cell biological behavior were determined after hypoxia reoxygenation treatment; cell biological behavior and the expression of related genes were determined after the transfection of SATB1 and beta-catenin siRNA; preeclampsia placenta and normal placenta tissues were collected and the expression of SATB1 and beta-catenin were determined. RESULTS: OD value, cell migration rate, mRNA contents of SATB1 and beta-catenin of H/R group were significantly lower than those of Nor group, cell apoptosis rate was higher than that of Nor group and the number of invasive cells was less than that of Nor group; OD value and bcl-2 mRNA content of SATB1-siRNA group were lower than those of NC group; cell apoptosis rate as well as Bax, Caspase-3, Caspase-6 and Caspase-9 mRNA contents were higher than those of NC group; cell migration rate as well as CTSB, CTSD, MMP2 and MMP9 mRNA contents of beta-catenin-siRNA group were lower than those of NC group; the number of invasive cells was less than that of NC group; the expression levels of SATB1 and beta-catenin in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue. CONCLUSIONS: Hypoxia can inhibit the expression of SATB1 and beta-catenin in the pathogenesis of preeclampsia, which can affect the proliferation, apoptosis, migration and invasion of cells. PMID- 27262069 TI - Protection mechanism of deacetylase inhibitor on spleen of rats with severe hemorrhagic shock. AB - OBJECTIVE: To explore the protection and molecular mechanism of histone deacetylase inhibitors (HDACIs) on the spleen of rats with hemorrhagic shock. METHODS: A total of 60 SPF male SD rats were selected for the modeling of severe hemorrhagic shock using the method of arterial and venous cannulation with the time-divided bleeding. The measurement of mean arterial blood pressure and blood lactic acid was used to verify the modeling. The modeled rats were randomly divided into shock group, shock + suberoylanilide hydroxamic acid (SAHA) group, shock + autogenous transfusion group and shock + SAHA + autogenous transfusion group. Three hours after the treatment, the spleen of rats was collected and TUNEL method was employed to detect the apoptosis of spleen cells in each group. The statistical analysis was performed. Afterwards, real-time PCR and western blot were employed to detect the expression of BCL-2, BAX and caspass3 in the spleen of rats in each group. RESULTS: A total of 53 rats had successful modeling of severe hemorrhagic shock, with success rate of 88%. Cell apoptosis in the severe hemorrhagic model group was the most serious. After the intervention of HDACIs and the autogenous transfusion, the tissue injury was a bit recovered. Cell apoptosis was least in the shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BCL-2 was significantly increased (P < 0.05), with highest relative expression of BCL-2 in shock + SAHA + autogenous transfusion group (P < 0.05). After the intervention of HDACIs and the autogenous transfusion, the relative expression of BAX was significantly decreased (P < 0.05), with lowest relative expression of BAX in the intervention group of single HDACIs. The change in the expression of caspass3 was similar to BAX, namely the relative expression of caspass3 was significantly decreased after the intervention of HDACIs and the autogenous transfusion (P < 0.05). CONCLUSIONS: HDACIs and autogenous transfusion can all protect the spleen injury because of the severe hemorrhagic shock. Its molecular mechanism may be related to the regulation on the expression of BCL 2/BAX and caspass3, which may affect the apoptosis process of cells. PMID- 27262070 TI - Study on prevention effect of Zishen Yutai pill combined with progesterone for threatened abortion in rats. AB - OBJECTIVE: To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats. METHODS: After pregnancy, 50 SPF female SD rats were selected and divided into control group, model group, progesterone group, Zishen Yutai pill group, and progesterone plus Zishen Yutai pill group (combination group), with 10 rats in each group. The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days. Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days. Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin, continuous for 10 days. Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days, and other treatments were the same as previous two groups. Abortion model were established then and live births, numbers of abortion and average rate of abortion were compared between the five groups. Peripheral blood was collected to detect the estradiol (E2) and progestational hormone (P), and obtain ratio of Th1/Th2 cytokines (IL-2, INF gamma, IL-4, IL-10). RESULTS: Significant more live births of rats were found in the control group compared with other four groups (P < 0.05) (P < 0.05). The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group, Zishen Yutai pill group and joint group (P < 0.05). The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group. The serum E2 level of P of rats in the control group, progesterone group, Zishen Yutai pill group and joint group were significant higher than that of abortion model group (P < 0.05). Serum levels of E2 and P of rats in the control group, progesterone group, Zishen Yutai pill group and joint group were not significant different (P > 0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group (P < 0.05). The maternal-fetal interface IL - 4/IL - 2, IL - 10/IL - 2 of model group were balanced deviating to Th1, while the IL-4/IL-2, IL-10/IL-2 of progesterone group, Zishen Yutai pill group and joint group were balanced deviating to Th2, and joint group' deviation was better than progesterone group and Zishen Yutai pill group (P < 0.05). CONCLUSIONS: Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion, which can obviously increase contents of maternal serums E2 and P, and regulate the Th1/Th2 balance with a remarkable effect. PMID- 27262071 TI - Correlation study of biological characteristics of non-small cell lung cancer A549 cells after transfecting plasmid by microbubble ultrasound contrast agent. AB - OBJECTIVE: To explore the role of the abnormal expression of miRNAs in the development process of non-small cell lung cancer and the feasibility of ultrasound microbubble-mediated gene therapy after transfecting antisense miRNA 224 and miRNA-122a plasmids into non-small cell lung cancer A549 cells. METHODS: Antisense miRNA-224 and miRNA-122a plasmids were transfected into non-small cell lung cancer A549 cells on the optimal ultrasound microbubble-mediated condition. We set up a control group. The cell proliferation activity, apoptosis, invasion ability were detected by MTT assay, Annexin V-PE, Transwell invasion experiment and colony formation assay, respectively. RESULTS: The expression of miRNA-224 decreased and the expression of miRNA-122a rose after the plasmids of target genes were transfected into non-small cell lung cancer A549 cells, and there were significant differences when compared with those of the control group (P < 0.05). After the plasmids of target genes were transfected into A549 cells, the growth of antisense miRNA-224 and miRNA-122a were inhibited, and the differences were significant as compared with the control group (P < 0.05). Besides, the inhibition of miRNA-122a group was the most significant and there was statistically significant difference as compared with miRNA-224 group (t = 4.694, P = 0.009). After the plasmids of target genes were transfected into A549 cells, the proportion of apoptotic cells increased, the invasive cells were decreased and the clone ability reduced, and also there was a significant difference as compared with those of the control group (P < 0.05). What's more, the apoptotic peak appeared in miRNA-122a group. Its invasion ability decreased most obviously (40.25 +/- 3.97/visual field), the number of clone ability was 104.93 +/- 4.87 and the inhibitory effect was the most obviously. There was statistically significant difference as compared with other groups (P < 0.05). CONCLUSIONS: A549 cells transfected by ultrasound microbubble-mediated antisense miRNA-224 and miRNA-122a plasmids possessed good transfection efficiency. The cell growth, invasion and colony-forming abilities of transfected A549 cells were suppressed, which laid a solid foundation for the gene therapy of non-small cell lung cancer. PMID- 27262072 TI - Expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in brain tissue of diabetic rats with ischemia reperfusion. AB - OBJECTIVE: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. METHODS: A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the brain tissue. RESULTS: The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group (P < 0.05). MMP-9 began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group (P < 0.05). CONCLUSIONS: The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus. PMID- 27262073 TI - Change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer treated by sorafenib. AB - OBJECTIVE: To study the change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer after treated by sorafenib. METHODS: Patients with advanced liver cancer admitted in our hospital were enrolled and treated with sorafenib. After two months of the treatment, their peripheral blood was collected. The immune cell subset and cytokines level were determined by flow cytometry and luminex technology. According to the reaction expressed by patients towards sorafenib, patients were divided into the response group and the no response group. The changes of the peripheral blood immune pattern and its correlation with prognosis of patients in the two groups were compared. RESULTS: Before and after treatment of sorafenib, there was no significant difference in the ratios of T cells, NK cells and their subtypes in peripheral blood of patients between the two groups; while after treatment the ratio of B cells and regulatory B cells (Breg) of patients in the response group was significant higher than that of the no response group (P < 0.05), and the prognosis conditions of patients with decreased ratio of Breg cells were better than other patients after undergoing chemotherapy. The levels of plasma cytokines IL-6, IL-10, IL-12, IL17, FIL-3L, IFN-gamma, TNF-alpha, MCP-1 and VEGF showed no significant differences. CONCLUSIONS: After treatment of sorafenib, the prognosis conditions of patients of advanced liver cancer with a reduced Breg ratio are better than patients with an unaltered or increased Breg ratio. The ratio of Breg in peripheral blood may be considered as early biological indicator for the prediction of the curative effects of sorafenib. PMID- 27262074 TI - The expression of MYH9 in osteosarcoma and its effect on the migration and invasion abilities of tumor cell. AB - OBJECTIVE: To determine the expression of non-muscle myosin heavy chain 9 (MYH9) in osteosarcoma and its effect on the migration and invasion abilities of tumor cell. METHODS: A total of 65 cases of osteosarcoma and 20 cases with benign osteochondroma who underwent resection operation in the Orthopaedics Department of our hospital from January 1st 2009 to January 1st 2015 were selected. Their mRNA levels of MYH9 were tested by qrt-PCR. Immunohistochemical method was used to examine the expression of MYH9 in osteosarcoma and the correlation between the positive expression of MYH9 and the clinicopathological features of patients was illustrated by statistical analysis. MYH9 was compounded artificially. The expression of MYH9 in SAOS2 osteosarcoma cells was decreased by siRNA. Scratch test was used to determine the change of SAOS2 cell migration ability after MYH9 silence. Transwell assay was employed to detect the change of cell invasion ability after MYH9 silence. RESULTS: The expression levels of mRNA of MYH9 and protein in osteosarcoma tissues were significantly higher than those in benign osteochondroma tissues. The high expression of MYH9 in osteosarcoma tissues was apparently related to the high Enneking classification (III classification) and lung metastasis. SiRNA of MYH9 could evidently decrease the expression level of MYH9 in SAOS2. The down-regulated expression of MYH9 could inhibit the migration and invasion abilities of SAOS2 cells. CONCLUSIONS: MYH9 shows a trend of high expression in osteosarcoma tissues, and its high expression is associated with features such as tumor invasion and metastasis. The down-regulated MYH9 can realize an anti-tumor effect by inhibiting the migration and invasion of osteosarcoma cells. PMID- 27262075 TI - Comparative study of the chitooligosaccharides effect on the proliferation inhibition and radiosensitization of three types of human gastric cancer cell line. AB - OBJECTIVE: To observe the chitooligosaccharides (COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line. MOTHODS: CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells, MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells. The clonogenic assay was used to detect the cell viability of 0, 1, 2, 4, 6 and 8 Gy (6 dose grades) in RAY group and RAY + COS group after X-ray, and the cell survival curve was used to analyze the sensitization enhancement ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY + COS group after 48 h treatment. RESULTS: COS inhibited the proliferation of three types of cells. The inhibition rate was positively correlated with the concentration of COS, and the susceptibility of MKN45 cells, SGC7901 cells and BGC823 cells to COS decreased in turn. The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY + COS group (P < 0.01). The cell viabilities of RAY + COS group were lower than those of RAY group at all the dose grades under X-ray exposure (P < 0.01), and the sensitization enhancement ratios of COS on BGC823 cells, MKN45 cells and SGC7901 cells were 1.06, 1.28 and 1.15, respectively. In controlled trials, apoptosis rate and percentage in the G2/M phase of three types of cells in RAY + COS group were higher than those in control group and RAY group, and percentage in the S phase and the G0/G1 phase in RAY + COS group were lower than those in the other two groups (P < 0.01). CONCLUSIONS: COS can inhibit the proliferation of three types of human gastric cancer cells and enhance the radiosensitivity by inducing apoptosis and G2/M phase arrest. PMID- 27262076 TI - Experiment research of cisplatin implants inhibiting transplantation tumor growth and regulating the expression of KLK7 and E-cad of tumor-bearing mice with gastric cancer. AB - OBJECTIVE: To study the influence of cisplatin implants on transplantation tumor growth and the expression of tissue kallikrein-7 (KLK7) and E-cadherin (E-cad) in tumor-bearing mice with gastric cancer. METHODS: BALB/c nude mice were collected as experimental animal and were randomly divided into model control group (Group A), tail intravenous injection of cisplatin group (Group B), intratumor injection of cisplatin group (Group C) and cisplatin implants treatment group (Group D). After the drugs intervening, the weight and volume of transplantation tumors were measured on Day 20, Day 30 and Day 40 and serum and KLK7 and E-cad contents in transplanted tumor tissue were examined. RESULTS: On Day 20, Day 30 and Day 40 after treatment, the weight and volume of transplantation tumors of tumor-bearing mice in four groups were different (Group A > Group B > Group C > Group D). The contents of KLK-7 and E-cad in tumor tissue and serum of tumor-bearing mice in four groups were different (Group A > Group B > Group C > Group D in KLK-7) and (Group A < Group B < Group C < Group D in E-cad). The weight and volume, and KLK7 and E-cad contents of transplantation tumors in four groups were significant difference (P < 0.05). CONCLUSION: Cisplatin implants can inhibit the growth of transplanted tumor tissue and down-regulated KLK7 expression and up-regulated E cad expression of tumor-bearing mice with gastric cancer. PMID- 27262077 TI - Encephalitis with convulsive status in an immunocompetent pediatric patient caused by Bartonella henselae. AB - Cat scratch's disease caused by Bartonella henselae, is known to be a self limited benign process in immunocompetent children. The association with neurologic manifestations is very uncommon especially in patient with no immunologic defects and in cases without specific treatment. A 7 years old male patient, without any immunocompromised defect, presented an atypic presentation of the cat scratch disease. The patient came to the hospital in two opportunities in a status epilepticus, in both cases the diagnosis was encephalitis by Bartonella henselae and the evolution with treatment was monitored with PCR (polymerase chain reaction) in cerebrospinal fluid and blood, as well as IFI (IgM, IgG) serology (indirect immunofluorescence). The patient had a favorable clinical and laboratory evolution for 6 months showing no recurrence of the disease. PMID- 27262078 TI - ZIka virus infection in Asia: Reappraisal on phylogenetic data of Asian lineage. PMID- 27262079 TI - Are efforts up to the mark? A cirrhotic state and knowledge about HCV prevalence in general population of Pakistan. PMID- 27262080 TI - Taeniasis vs cysticercosis infection routes. PMID- 27262081 TI - Light-responsive multillamellar vesicles in coumaric acid/alkyldimethylamine oxide binary systems: Effects of surfactant and hydrotrope structures. AB - Herein, we report a series of novel light-responsive multilamellar vesicles based on the surfactant/hydrotrope binary systems. The phase behaviors of alkyldimethylamine oxide (CmDMAO, m=10, 12, 14) and trans-coumaric acid (trans CA) isomerides, including trans-ortho-coumaric acid (trans-OCA), trans-meta coumaric acid (trans-MCA) and trans-para-coumaric acid (trans-PCA), show that the multilamellar vesicle (MLV) formation region is commonly presented in the trans CA/CmDMAO systems except trans-PCA/C12DMAO. Moreover, the molecular structures of CmDMAO and trans-CA affect the multilamellar vesicle formation region significantly. Generally speaking, the bigger the m, the larger the MLV region. Various techniques such as rheology, polarized optical microscopy (POM), (1)H NMR, (2)H NMR, cryogen transmission electron microscopy (cryo-TEM) and freeze fracture transmission electron microscopy (FF-TEM) are used to characterize the aggregate structures. The multilamellar vesicles can transform into a homogeneous and transparent micelle phase or a two-phase system in the trans-OCA/CmDMAO binary systems under UV light irradiation, which depends on the chain length of CmDMAO and the molar ratio of [trans-OCA]/[CmDMAO]. Specifically, the light stimuli response of multilamellar vesicles in the trans-OCA/C12DMAO system is representatively studied in detail. UV-vis spectra and (1)H NMR measurements illustrate that the light-induced trans-OCA to cis-OCA isomerization is essential during the transitions and the light-induced two-phase formation is attributed to the enrichment of surfactants, because the trans-cis isomerization can not only strengthen the hydrophilicity of cis-OCA but also increase the steric hindrance between cis-OCA and C12DMAO, and thereby altering the morphology of aggregate and the rheological response of bulk phase significantly. PMID- 27262082 TI - Screening and identification of the metabolites in rat urine and feces after oral administration of Lycopus lucidus Turcz extract by UHPLC-Q-TOF-MS mass spectrometry. AB - Lycopus lucidus Turcz has been used as a kind of edible and medicinal material in eastern Asian countries. It has various bioactivities, including treatment of menstrual disorder, amenorrhea, menstrual cramps, inflammation, and cardiovascular diseases. However, the in vivo metabolism of L. lucidus Turcz extract is still not well described. In this study, L. lucidus Turcz extracts were administered to rats. Urine and fecal samples were collected at the difference periods (0-12h, 12-24h, and 24-36h). Ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole time-of flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed to characterize and identify the metabolites. A total of 17 metabolites in feces and 19 metabolites in urine were tentatively identified by means of accurate mass and characteristic fragment ions. The results show that glucuronidation and sulfation are the major metabolic reactions. This study is the first reported analysis and characterization of the metabolites and the proposed metabolic pathways of bioactive components might provide further understanding of the metabolic fate of the chemical constituents after oral administration of L. lucidus Turcz extract in rats. PMID- 27262083 TI - Monitoring of antifungal drugs in biological samples using ultrasonic-assisted supramolecular dispersive liquid-liquid microextraction based on solidification of a floating organic droplet. AB - A new method for the simultaneous determination of the three antifungal drugs using ultrasonic-assisted supramolecular dispersive liquid-liquid microextraction based on solidification of a floating organic droplet (UASMDLLME-SFO) was proposed. The supramolecular solvents produced from reversed micelles of 1 dodecanol (extraction solvent) in tetrahydrofuran (THF) were injected into the aqueous sample solution. Reverse micelle coacervates were produced in situ through self-assembly processes. The antifungal drugs were extracted from the aqueous sample into a supramolecular solvent. Sonication accelerated the mass transfer of the target analytes into the supramolecular solvent phase and enhanced the dispersion process. Some parameters affecting the extraction efficiency such as type and volume of the extraction solvent, pH, volume of the disperser solvent and ultrasound extraction time were investigated. Under optimum conditions, the limits of detections for ketoconazole, clotrimazole and miconazole ranged from 0.08 to 1.3MUgL(-1) and the relative standard deviations (RSDs, n=5)<6% were obtained. The method was successfully applied for preconcentration of the three drugs in biological and water samples. PMID- 27262084 TI - Lactobacillus acidophilus attenuates Aeromonas hydrophila induced cytotoxicity in catla thymus macrophages by modulating oxidative stress and inflammation. AB - The pathogenesis of Aeromonas hydrophila, a potent fish pathogen, is attributed to its ability to cause motile aeromonad septicaemia leading to apoptosis in a myriad of fish species, including freshwater carp Catla catla. However, the underlying mechanism of antagonistic activity of probiotics against A. hydrophila induced apoptosis is not elucidated due to lack of appropriate in-vitro models. This study reported that the exposure of catla thymus macrophages (CTM) to A. hydrophila markedly induced cellular injuries as evidenced by elevated levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), increased apoptosis, DNA damage and decreased cellular viability. Flow cytometry analysis and Annexin-V/propidium iodide assay further confirmed increased ROS positive cells leading to cell death after infection. The quantitative real-time PCR analysis, also revealed upregulation of inducible nitric-oxide synthase (iNOS), pro-inflammatory cytokine (TNFalpha), cyclooxygenase2 (COX-2) and downregulation of anti-inflammatory cytokine (IL-10). Pretreatment of cells with probiotic, Lactobacillus acidophilus attenuated A. hydrophila induced apoptosis as evident from the decrease in the levels of ROS, RNS and DNA damage. Significant increase (P<=0.05) in expression of TNFalpha and IL-10 and decrease in iNOS and COX-2 was observed on probiotic stimulation. In-vivo study using catla fingerlings confirmed similar pattern of ROS, iNOS, NO production and cytokine expression in thymus. This study provides a comprehensive insight into the mechanistic basis of L. acidophilus induced macrophage mediated inflammatory response against A. hydrophila in CTM cells. Further, it speculates the possibility of using cost effective in-vitro models for screening probiotic candidates of therapeutic potential in aquaculture industry. PMID- 27262085 TI - Nursing students' perceptions of community care and other areas of nursing practice - A review of the literature. AB - OBJECTIVES: To review recent literature on student nurses' perceptions of different areas of nursing practice, in particular community care. Healthcare is changing from care delivery in institutional settings to care to patients in their own homes. Problematic is that nursing students do not see community care as an attractive line of work, and their perceptions of community care do not reflect the realities of the profession. Understanding the factors influencing the perception of the professional field is important to positively influence students' willingness to see community nursing as a future profession. DESIGN: Literature search with accompanying narrative synthesis of primary research. DATA SOURCES: ERIC((r)), PsycInfo((r)), Pubmed((r)), and CINAHL((r)) (2004-2014) databases using the search terms: 'nursing student', 'student nurse', 'community care', 'community nurse', 'image', 'attitude', and 'perception'. REVIEW METHODS: After screening 522 retrieved article titles with abstracts, the number of articles was reduced based upon specified inclusion/exclusion criteria leading to inclusion of 34. Evaluation of the references in those articles yielded an additional 5 articles. A narrative synthesis of those articles was created to uncover students' perception of community care, other areas of professional practice, and the factors influencing those perceptions. RESULTS: 39 articles were selected. Results show that many nursing students begin their education with a lay person's conception of the profession, shaped by media representations. Work placements in different settings offer clinical experience that helps students orient themselves towards a future profession. Students prefer hospitals as a place of work, because of the acute nature and technologically advanced level of care offered there. Few students perceive mental health and elderly care as appealing. Perceptions of community care can vary widely, the most prevalent view being that it is unattractive because of its chronic care profile, with little technical skill, untrained workers, and a high workload. However, another view is that it offers challenging and meaningful work because of the variety of caregiving roles and the opportunity to work independently. CONCLUSIONS: Few nursing students choose community nursing as a future profession. They have a limited and often mistaken view of community care, and they underestimate the field's complexity because it is less visible than in the environment of acute care. Providing students with specific curricular content and employing a structured approach to preparation for work placement could help build a more positive perception of community care, leading to more students seeing/choosing community care as a desirable field of work. PMID- 27262086 TI - BDNF serum levels in schizophrenic patients during treatment augmentation with sarcosine (results of the PULSAR study). AB - AIM: Finding a relationship between schizophrenia symptoms severity and initial level of BDNF and its changes during augmentation of antipsychotic treatment with sarcosine. METHOD: 57 individuals with schizophrenia with predominantly negative symptoms completed a 6-month RCT prospective study. The patients received 2g of sarcosine (n=27) or placebo (n=30) daily. At the beginning, after 6 weeks and 6 months BDNF levels were measured. Severity of symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: BDNF serum levels were stable after 6 weeks and 6 months in both groups. We noted improvement in negative symptoms, general psychopathology and total PANSS score in sarcosine group comparing to placebo, however there was no correlations between serum BDNF concentrations and PANSS scores in all assessments. Initial serum BDNF concentrations cannot be used as a predictor of the improvement resulting from adding sarcosine. CONCLUSIONS: Our results indicate that either BDNF is not involved in the NMDA-dependent mechanism of sarcosine action or global changes in BDNF concentrations induced by amino acid cannot be detected in blood assessments. PMID- 27262087 TI - Patients with schizophrenia are less prone to interpret virtual others' empathetic questioning as helpful. AB - Individuals with schizophrenia are impaired in their neurocognition and present cognitive biases. These impairments may lead to a deficit in recognizing helping intentions of others. To investigate recognition of help, we designed a card guessing game (Virtual Help Recognition Paradigm) involving two successive virtual agents asking questions to the participant at different moments of the game. These questions were either empathetic (i.e. on the subject's feelings) or non-empathetic (i.e. on technical aspects of the game). We assessed how much the participant felt that the virtual agent had helped him and, her attitude and personality traits. We measured how much the participant trusted the virtual agent with a monetary allocation procedure. Twenty individuals with schizophrenia and twenty healthy controls were recruited. The controls' ratings demonstrated that they interpreted empathetic questioning as helping and rewarded it positively with an increased monetary allocation. Participants with schizophrenia had a reduced perception of the differences between the two agents. Only the rating concerning the "interest/attention" of the agent toward these participants yielded significant differences among conditions. Hypothetically, individuals with schizophrenia take into account the fact they are the object of another's attention, but may fail to infer a helping intention and to behave accordingly. PMID- 27262088 TI - Differences in knowledge of dementia among older adults with normal cognition, mild cognitive impairment, and dementia: A representative nationwide sample of Korean elders. AB - OBJECTIVE: Lack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia. METHODS: A representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD. RESULTS: The percentage of correct responses was only 62%. The item 'A person who remembers things that happened in the past does not have dementia' was answered correctly (false) by only 24.8-27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group. CONCLUSIONS: Efforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay. PMID- 27262089 TI - Exposure to physical and sexual violence prior to imprisonment predicts mental health and substance use treatments in prison populations. AB - The present study aimed to establish rates of exposure to physical or sexual violence (PSV) prior to imprisonment for prisoners in Spain and to explore whether people exposed to PSV access mental health treatment during imprisonment. In a sample of 2484 male and 225 female prisoners, socio-demographic variables, exposure to PSV prior to imprisonment and mental health treatments during imprisonment were assessed. Frequencies were calculated as per cent values with 95% confidence intervals (CI). The Risk Ratio (RR) of PSV and other socio demographic variables to associate with mental health treatment during imprisonment was established. History of PSV was present in 35.2% (95% CI: 33.3 37.0) of the male and 40.0% (95% CI: 33.9-46.8) of the female prisoners. 70.7% (95% CI: 67.8-73.9) of the male and 76.9% (95% CI: 67.7-86.0) of the female prisoners with prior exposure to PSV were in mental health treatment during imprisonment. PSV was a significant predictor of mental health treatment during imprisonment in male (RR: 2.79; 95% CI 2.44-2.92) and female (RR: 1.94; 95% CI 1.76-2.23) prisoners. Most people with exposure to PSV prior to imprisonment access mental health treatment during imprisonment. Treatments may have to focus more on traumatic experiences. PMID- 27262090 TI - The current state of accidents involving choking on mochi (glutinous rice cakes) during New Year's in Japan and measures to prevent them: A study focusing on the elderly. PMID- 27262091 TI - Hydrothermal carbonisation of poultry litter: Effects of treatment temperature and residence time on yields and chemical properties of hydrochars. AB - In this study, hydrochars were prepared by hydrothermal carbonisation (HTC) of poultry litter (PL) at temperatures between 150-300 degrees C with residence times of 30, 120 and 480min. The effects of treatment temperature and residence time on the yield and composition of hydrochar were investigated. Both treatment temperature and residence time effects were observed however, the effect of residence time was lower. The results indicated that the HHV was improved by up to 25.17% and the overall ash in hydrochar was significantly lower compared to PL, however this coincided with a lower hydrochar yield. PMID- 27262092 TI - Evaluation of the integrated hydrothermal carbonization-algal cultivation process for enhanced nitrogen utilization in Arthrospira platensis production. AB - Sustainable microalgal cultivation at commercial scale requires nitrogen recycling. This study applied hydrothermal carbonization to recover N of hot water extracted Arthrospira platensis biomass residue into aqueous phase (AP) under different operation conditions and evaluated the N utilization, biomass yield and quality of A. platensis cultures using AP as the sole N source. With the increase of temperature at 190-210 degrees C or reaction time of 2-3h, the N recovery rate decreased under nitrogen-repletion (+N) cultivation, while contrarily increased under nitrogen-limitation (-N) cultivation. Under +N biomass accumulation in the cultures with AP under 190 degrees C was enhanced by 41-67% compared with that in NaNO3, and the highest protein content of 51.5%DW achieved under 200 degrees C-2h was also 22% higher. Carbohydrate content of 71.4%DW under -N cultivation achieved under 210 degrees C-3h was 14% higher than that in NaNO3. HTC-algal cultivation strategy under -N mode could save 60% of conventional N. PMID- 27262093 TI - Facile synthesis of pectin-stabilized magnetic graphene oxide Prussian blue nanocomposites for selective cesium removal from aqueous solution. AB - This work focused on the development of pectin-stabilized magnetic graphene oxide Prussian blue (PSMGPB) nanocomposites for removal of cesium from wastewater. The PSMGPB nanocomposite showed an improved adsorption capacity of 1.609mmol/g for cesium, compared with magnetic graphene oxide Prussian blue, magnetic pectin Prussian blue, and magnetic Prussian blue nanocomposites, which exhibited adsorption capacities of 1.230, 0.901, and 0.330mmol/g, respectively. Increased adsorption capacity of PSMGPB nanocomposites was attributed to the pectin stabilized separation of graphene oxide sheets and enhanced distribution of magnetites on the graphene oxide surface. Scanning electron microscopy images showed the effective separation of graphene oxide sheets due to the incorporation of pectin. The optimum temperature and pH for adsorption were 30 degrees C and 7.0, respectively. A thermodynamic study indicated the spontaneous and the exothermic nature of cesium adsorption. Based on non-linear regression, the Langmuir isotherm fitted the experimental data better than the Freundlich and Tempkin models. PMID- 27262095 TI - Surface sorption and nanoparticle production as a silver detoxification mechanism of the freshwater alga Parachlorella kessleri. AB - SEM, EDS, TEM, FTIR and UV-vis analysis were used to investigate the biosorption, bioaccumulation and bioreduction of silver by the freshwater green alga Parachlorella kessleri. The dead algal biomass showed high potential for silver removal; 75% of silver was removed within 2min. Surface sorption was the main mechanism; bioreduction contributed to the biosorption only to a small extent. In the presence of living P. kessleri cells a 68% decrease of silver concentration was observed within 24h, but subsequently the majority of silver was released back into the solution within the next 14days. According to UV-vis spectrometry, silver nanoparticles were formed in that time. The nanoparticles produced by the alga exhibited a lower toxicity against algal cells than silver ions at the same silver concentrations. The study demonstrated that living algal cells used a combination of two main mechanisms (sorption and reduction) for silver detoxification in their environment. PMID- 27262094 TI - Effects of salinity build-up on the performance of an anaerobic membrane bioreactor regarding basic water quality parameters and removal of trace organic contaminants. AB - The effects of elevated inorganic salt concentration on anaerobic membrane bioreactor (AnMBR) treatment regarding basic biological performance and trace organic contaminant (TrOC) removal were investigated. A set of 33 TrOCs were selected to represent pharmaceuticals, steroids, and pesticides in municipal wastewater. Results show potential adverse effects of increase in the bioreactor salinity to 15g/L (as NaCl) on the performance of AnMBR with respect to chemical oxygen demand removal, biogas production, and the removal of most hydrophilic TrOCs. Furthermore, a decrease in biomass production was observed as salinity in the bioreactor increased. The removal of most hydrophobic TrOCs was high and was not significantly affected by salinity build-up in the bioreactor. The accumulation of a few persistent TrOCs in the sludge phase was observed, but such accumulation did not vary significantly as salinity in the bioreactor increased. PMID- 27262096 TI - Structure modification and extracellular polymeric substances conversion during sewage sludge biodrying process. AB - Biodrying, an economical and energy-saving biomass waste treatment, removes water from waste using the biological heat generated by organic matter degradation. Technical limitations associated with dewatering complicate the biodrying of sewage sludge. This study investigated the sludge alteration associated with its water removal, focusing on sludge form, extracellular polymeric substances, and free water release. An auto-feedback control technology was used for the biodrying; a scanning electron microscope was used to record the morphological change; three-dimensional excitation-emission matrix fluorescence spectroscopy was used to analyze extracellular polymeric substances (EPS) variation, and time domain reflectometry was used to assess the free water release. Over the 20-day biodrying, there was a 62% water removal rate during the first thermophilic phase. Biodrying created a hollow and stratified sludge structure. Aromatic proteins and soluble microbial byproducts in the EPS were significantly degraded. The thermophilic phase was the phase resulting in the greatest free water release. PMID- 27262097 TI - Development of a real-time bioprocess monitoring method for docosahexaenoic acid production by Schizochytrium sp. AB - Oxygen uptake rate (OUR) and respiratory quotient (RQ) are key respiratory parameters for docosahexaenoic acid (DHA) production by Schizochytrium sp. HX-308 under dissolved oxygen limited conditions. To investigate the relationship of OUR and RQ with culture status, three independent cultures with different aeration rates were performed in a 50L bioreactor. OUR was found to be positively correlated with the aeration rate, which reflected the oxygen supply level in each culture. The highest biomass, reaching 124.5g/L, was achieved under the highest OUR. DHA content was found to be highly correlated with the RQ value, and the highest DHA content (44.85% in total fatty acids, w/w) was achieved in the highest RQ level, which implies that the polyketide synthase pathway was more active. OUR and RQ, which reflect the physiological state of microorganisms, are suggested as synergistic real-time bioprocess monitoring parameters for DHA fermentation. PMID- 27262099 TI - Prevalence of Autoimmune Disease Among Patients With Lung Cancer: Implications for Immunotherapy Treatment Options. PMID- 27262098 TI - Long-term effects of ZnO nanoparticles on nitrogen and phosphorus removal, microbial activity and microbial community of a sequencing batch reactor. AB - The performance, microbial activity, and microbial community of a sequencing batch reactor (SBR) were investigated under the long-term exposure of ZnO nanoparticles (ZnO NPs). Low ZnO NPs concentration (less than 5mg/L) had no obvious effect on the SBR performance, whereas the removals of COD, NH4(+)-N, and phosphorus were affected at 10-60mg/L ZnO NPs. The variation trend of nitrogen and phosphorus removal rate was similar to that of microbial enzymatic activity with the increase of ZnO NPs concentrations. The richness and diversity of microbial community showed obvious variations at different ZnO NPs concentrations. ZnO NPs appeared on the surface and cell interior of activated sludge, and the Zn contents in the effluent and activated sludge increased with the increase of ZnO NPS concentration. The present results provide use information to understand the effect of ZnO NPS on the performance of wastewater biological treatment systems. PMID- 27262100 TI - rs11895168 C allele and the increased risk of breast cancer in Isfahan population. AB - OBJECTIVES: Some of the single nucleotide polymorphisms in EebB4 gene have been studied to date in order for finding their relevance to the risk of breast cancer. However, no study has been conducted to investigate the importance of rs11895168, a microRNA-related SNP located in ErbB4 3'UTR, in breast tumors. In this paper, we investigated the frequency and association between rs11895168 and breast cancer. MATERIALS AND METHODS: The rs11895168 was genotyped in 364 samples collected from 172 breast cancer patients and 192 healthy participants, using Tetra-primer ARMS PCR. The frequency of genotypes was analyzed to find the association between rs11895168 and breast cancer risk and also clinicopathological characteristics of patients. RESULTS: our in silico studies suggested that different alleles at rs11895168 affect the binding strength of miR 1276, a potential tumor suppressor. Statistical analysis showed a significant association between rs11895168 C allele-harboring genotypes and increased breast cancer risk. CONCLUSION: rs11895168 C allele is strongly and significantly associated with the increased risk of breast cancer and positivity of ER/PR tumor cells. PMID- 27262101 TI - Analysis of the carbohydrate-binding-module from Fragaria x ananassa alpha-L arabinofuranosidase 1. AB - alpha-L-arabinofuranosidases (EC 3.2.1.55) are enzymes involved in the catabolism of several cell-wall polysaccharides such as pectins and hemicelluloses, catalyzing the hydrolysis of terminal non-reducing alpha-L-arabinofuranosil residues. Bioinformatic analysis of the aminoacidic sequences of Fragaria x ananassa alpha-L-arabinofuranosidases predict a putative carbohydrate-binding module of the family CBM_4_9, associated to a wide range of carbohydrate affinities. In this study, we report the characterization of the binding affinity profile to different cell wall polysaccharides of the putative CBM of alpha-L arabinofuranosidase 1 from Fragaria x ananassa (CBM-FaARA1). The sequence encoding for the putative CBM was cloned and expressed in Escherichia coli, and the resultant recombinant protein was purified from inclusion bodies by a Nickel affinity chromatography under denaturing conditions. The refolded recombinant protein was then subjected to binding assays and affinity gel electrophoresis, which indicated its ability to bind cellulose and also high affinity for homogalacturonans. PMID- 27262102 TI - Clinical and analytical performance of the PapilloCheck HPV-Screening assay using the VALGENT framework. AB - BACKGROUND: The benefit of HPV testing for cervical cancer screening and disease management has been shown in many recent studies and is part of several new evidence-based guidelines. Assessment of emerging HPV tests in this context is essential, using well-annotated samples, such as those generated via the Validation of Genotyping Tests-HPV (VALGENT) framework. OBJECTIVE: Our aim was to assess the PapilloCheck HPV assay in terms of absolute and relative accuracy for primary cervical cancer screening, using a standard comparator test (GP5+/6+EIA)already validated in randomised trials. STUDY DESIGN: Type-specific HPV prevalence was stratified by age and cytology grade and compared with the luminex typing assay incorporating a GP5+6+ PCR (GP5+/6+ LMNX Assay). Clinical outcomes were compared with GP5+/6+EIA. RESULTS: Prevalence of hrHPV types (high risk HPV) increased with severity of cytology. The concordance between PapilloCheck and the GP5+/6+ LMNX Assay was excellent when assessed at the qualitative hrHPV presence/absence level also at the type-specific level in the whole population and in women over 30 years of age. Absolute clinical sensitivity and specificity of the PapilloCheck was high and ranged between 95.5% and 98.2% for sensitivity and between 82.7% and 91.6% for specificity, depending on the outcome and population. CONCLUSION: The sensitivity and specificity of this assay for the outcomes of CIN2+ were similar to those of the standard comparator assay, GP5+/6+ EIA. PMID- 27262103 TI - From BPA to its analogues: Is it a safe journey? AB - Bisphenol-A (BPA) is one of the most abundant synthetic chemicals in the world due to its uses in plastics. Its widespread exposure vis-a-vis low dose effects led to a reduction in its safety dose and imposition of ban on its use in infant feeding bottles. This restriction paved the way for the gradual market entry of its analogues. However, their structural similarity to BPA has put them under surveillance for endocrine disrupting potential. The application of these analogues is increasing and so are the studies reporting their toxicity. This review highlights the reasons which led to the ban of BPA and also reports the exposure and toxicological data available on its analogues. Hence, this compilation is expected to answer in a better way whether the replacement of BPA by these analogues is safer or more harmful? PMID- 27262104 TI - Perfluorooctanoic acid exposure alters polyunsaturated fatty acid composition, induces oxidative stress and activates the AKT/AMPK pathway in mouse epididymis. AB - Perfluorooctanoic acid (PFOA) is a degradation-resistant compound with a carbon fluorine bond. Although PFOA emissions have been reduced since 2000, it remains persistent in the environment. Several studies on laboratory animals indicate that PFOA exposure can impact male fertility. Here, adult male mice received either PFOA (1.25, 5 or 20 mg/kg/d) or an equal volume of water for 28 d consecutively. PFOA accumulated in the epididymis in a dose-dependent manner and resulted in reduced epididymis weight, lower levels of triglycerides (TG), cholesterol (CHO), and free fatty acids (FFA), and activated AKT/AMPK signaling in the epididymis. Altered polyunsaturated fatty acid (PUFA) compositions, such as a higher arachidonic acid:linoleic acid (AA:LA) ratio, concomitant with excessive oxidative stress, as demonstrated by increased malonaldehyde (MDA) and decreased glutathione peroxidase (GSH-Px) in the epididymis, were observed in epididymis tissue following treatment with PFOA. These results indicate that the epididymis is a potential target of PFOA. Oxidative stress and PUFA alteration might help explain the sperm injury and male reproductive dysfunction induced by PFOA exposure. PMID- 27262105 TI - Determination of n-alkanes contamination in soil samples by micro gas chromatography functionalized by multi-walled carbon nanotubes. AB - A new method for separation of 11 n-alkanes: octane, o-nonane, n-decane, n undecane, n-dodecane, n-tridecane, n-tetradecane, n-pentdecne, n-hexadecath, heptadecane, n-octadecane in soil samples was developed. Kuderna-Danish (K.D.) concentrator enrichment prior to ultrasonic extraction and the silicone chromatography column purification and with gas chromatography flame ionization detection (GC-FID) could be used for n-alkanes determination. The micro channels of open tubular column were fabricated onto a silicon wafer to replace the quartz capillary chromatographic column. The column structure and analysis parameters that affected the column separation were investigated and optimized. Under optimal conditions, the extract reagent was centrifuged and collected. A silicone chromatography column and a K.D. concentrator were used for further clean-up and enrichment. Using this method, the limits of detection (LOD) and limits of quantification (LOQ) were obtained in the range of 0.03-0.15 and 0.1-0.5 mg kg( 1) in soil samples, respectively. The relative standard deviation (RSD) was under 12%. The optimized procedure that presented good analytical performance (with recoveries ranging from 56.5% to 89.2%), was successfully applied to determine n alkane content in farmland soil samples adjacent to a highway. The results showed that the MWCNTs-functionalized column is capable of separating the alkane contaminations with high resolution in about 3 min, which is much shorter than that of GC-MS and other conventional analytical methods, demonstrating its great potential for rapid analysis. PMID- 27262106 TI - Bioanalytical method development and validation for the determination of glycine in human cerebrospinal fluid by ion-pair reversed-phase liquid chromatography tandem mass spectrometry. AB - A LC-MS/MS method has been developed and validated for the determination of glycine in human cerebrospinal fluid (CSF). The validated method used artificial cerebrospinal fluid as a surrogate matrix for calibration standards. The calibration curve range for the assay was 100-10,000ng/mL and (13)C2, (15)N glycine was used as an internal standard (IS). Pre-validation experiments were performed to demonstrate parallelism with surrogate matrix and standard addition methods. The mean endogenous glycine concentration in a pooled human CSF determined on three days by using artificial CSF as a surrogate matrix and the method of standard addition was found to be 748+/-30.6 and 768+/-18.1ng/mL, respectively. A percentage difference of -2.6% indicated that artificial CSF could be used as a surrogate calibration matrix for the determination of glycine in human CSF. Quality control (QC) samples, except the lower limit of quantitation (LLOQ) QC and low QC samples, were prepared by spiking glycine into aliquots of pooled human CSF sample. The low QC sample was prepared from a separate pooled human CSF sample containing low endogenous glycine concentrations, while the LLOQ QC sample was prepared in artificial CSF. Standard addition was used extensively to evaluate matrix effects during validation. The validated method was used to determine the endogenous glycine concentrations in human CSF samples. Incurred sample reanalysis demonstrated reproducibility of the method. PMID- 27262107 TI - Development and validation of a selective, sensitive and stability indicating UPLC-MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance. AB - In this study a sensitive and selective gradient reverse phase UPLC-MS/MS method was developed for the simultaneous determination of six process related impurities viz., Imp-I, Imp-II, Imp-III, Imp-IV, Imp-V and Imp-VI in darunavir. The chromatographic separation was performed on Acquity UPLC BEH C18 (50 mm*2.1mm, 1.7MUm) column using gradient elution of acetonitrile-methanol (80:20, v/v) and 5.0mM ammonium acetate containing 0.01% formic acid at a flow rate of 0.4mL/min. Both negative and positive electrospray ionization (ESI) modes were operated simultaneously using multiple reaction monitoring (MRM) for the quantification of all six impurities in darunavir. The developed method was fully validated following ICH guidelines with respect to specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, robustness and sample solution stability. The method was able to quantitate Imp I, Imp-IV, Imp-V at 0.3ppm and Imp-II, Imp-III, and Imp-VI at 0.2ppm with respect to 5.0mg/mL of darunavir. The calibration curves showed good linearity over the concentration range of LOQ to 250% for all six impurities. The correlation coefficient obtained was >0.9989 in all the cases. The accuracy of the method lies between 89.90% and 104.60% for all six impurities. Finally, the method has been successfully applied for three formulation batches of darunavir to determine the above mentioned impurities, however no impurity was found beyond the LOQ. This method is a good quality control tool for the trace level quantification of six process related impurities in darunavir during its synthesis. PMID- 27262108 TI - Arachidonic acid metabolomic study of BPH in rats and the interventional effects of Zishen pill, a traditional Chinese medicine. AB - Zishen pill (ZSP) is a traditional Chinese medicine (TCM) used to treat benign prostatic hyperplasia (BPH). The study used a metabolomic approach based on UHPLC MS/MS to profile arachidonic acid (AA) metabolic changes and to investigate the interventional mechanisms of ZSP in testosterone- induced BPH rats. In order to explore the potential therapeutic effect of ZSP, rat models were constructed and orally administrated with ZSP. Plasma and urine samples were collected after four weeks and then eleven potential biomarkers (15-HETE, 12-HETE, TXA2, 5-HETE, AA, PGI2, PGF2alpha, 8-HETE, PGD2, PGE2 and LTB4) were identified and quantified by UHPLC-MS/MS. The chromatographic separation was carried out with gradient elution using a mobile phase comprised of 0.05% formic acid aqueous solution (pH=3.3) (A) and acetonitrile: methanol (80:20, V/V) (B), and each AA metabolites was measured using electrospray ionization source with negative mode and multiple reaction monitoring. The eleven biomarkers in BPH group rat plasma and urine were significant higher than those in sham group rats. Using the potential biomarkers as a screening index, the results suggest that ZSP can potentially reverse the process of BPH by partially regulating AA metabolism through refrain the expression of cyclooxygenase (COX) and lipoxygenase (LOX). This study demonstrates that a metabolomic strategy is useful for identifying potential BPH biomarkers and investigating the underlying mechanisms of a TCM in BPH treatment. PMID- 27262109 TI - Systematic development of a group quantification method using evaporative light scattering detector for relative quantification of ginsenosides in ginseng products. AB - The determination for the contents of multi-components in ginseng products has come to the fore by demands of in-depth information, but the associated industries confront the high cost of securing pure standards for the continuous quality evaluation of the products. This study aimed to develop a prospective high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) method for relative quantification of ginsenosides in ginseng products without a considerable change from the conventional gradient analysis. We investigated the effects of mobile phase composition and elution bandwidth, which are potential variables affecting the ELSD response in the gradient analysis. Similar ELSD response curves of nine major ginsenosides were obtained under the identical flow injection conditions, and the response increased as the percentage of organic solvent increased. The nine ginsenosides were divided into three groups to confirm the effect of elution bandwidth. The ELSD response significantly decreased in case of the late eluted ginsenoside in the individual groups under the isocratic conditions. With the consideration of the two important effects, stepwise changes of the gradient condition were carried out to reach a group quantification method. The inconsistent responses of the nine ginsenosides were reconstituted to three normalized responses by the stepwise changes of the gradient condition, and this result actualized relative quantification in the individual groups. The availability was confirmed by comparing the ginsenoside contents in a base material of ginseng products determined by the direct and group quantification method. The largest difference in the determination results from the two methods was 8.26%, and the difference of total contents was only 0.91%. PMID- 27262110 TI - The impact of partial hepatectomy on oxidative state in the liver remnant - An in vivo swine model. AB - BACKGROUND: Previous studies on oxidative state after partial hepatectomy (PHx) report conflicting data on levels of glutathione (GSH) and are mainly presented in rodent models by methodology less sensitive than the present technologies. The current swine model presents GSH levels and the following genetic response post PHx, utilizing an analytical platform more sensitive and precise than earlier available. METHOD: Twelve pigs were randomized to a PHx- and a control group (n=6 in each). The PHx group had a 60% hepatectomy. Serial in vivo liver biopsies during 12h of anaesthesia post-PHx were analyzed for GSH by liquid chromatography mass spectrometry (LC-MS/MS). Transcriptional alterations of genes (GS, GCLM, GCLC, GR, HGF, NFE2L2, TGFbeta1) regulating GSH synthesis were measured by real time PCR. RESULTS: No difference was detected between the GSH levels in the PHx- and the control group during the experiment (P=0.247). Still, decreased gene expression of GS (P=0.026) and NFE2L2 (P=0.014) the first nine hours, and a decrease of TGFbeta1 (P=0.029) the first seven hours post-PHx was seen in the liver remnant. CONCLUSION: The results show that the liver has an extended capacity to maintain GSH homeostasis during major stress and parenchymal loss, even at the early onset of such trauma. This observation was not explained by increased expression of key genes in GSH pathways. Consequently, the results indicate an inherent compensatory capacity to maintain GSH homeostasis in the reduced organ. PMID- 27262111 TI - Engineering AAV receptor footprints for gene therapy. AB - Adeno-associated viruses (AAV) are currently at the forefront of human gene therapy clinical trials as recombinant vectors. Significant progress has been made in elucidating the structure, biology and tropisms of different naturally occurring AAV isolates in the past decade. In particular, a spectrum of AAV capsid interactions with host receptors have been identified and characterized. These studies have enabled a better understanding of key determinants of AAV cell recognition and entry in different hosts. This knowledge is now being applied toward engineering new, lab-derived AAV capsids with favorable transduction profiles. The current review conveys a structural perspective of capsid-glycan interactions and provides a roadmap for generating synthetic strains by engineering AAV receptor footprints. PMID- 27262112 TI - BDNF Val66Met Genotype Interacts With a History of Simulated Stress Exposure to Regulate Sensorimotor Gating and Startle Reactivity. AB - Reduced expression of Brain-Derived Neurotrophic Factor (BDNF) has been implicated in the pathophysiology of schizophrenia. The BDNF Val66Met polymorphism, which results in deficient activity-dependent secretion of BDNF, is associated with clinical features of schizophrenia. We investigated the effect of this polymorphism on Prepulse Inhibition (PPI), a translational model of sensorimotor gating which is disrupted in schizophrenia. We utilized humanized BDNFVal66Met (hBDNFVal66Met) mice which have been modified to carry the Val66Met polymorphism, as well as express humanized BDNF in vivo. We also studied the long term effect of chronic corticosterone (CORT) exposure in these animals as a model of history of stress. PPI was assessed at 30ms and 100ms interstimulus intervals (ISI). Analysis of PPI at the commonly used 100ms ISI identified that, irrespective of CORT treatment, the hBDNFVal/Met genotype was associated with significantly reduced PPI. In contrast, PPI was not different between hBDNFMet/Met and hBDNFVal/Val genotype mice. At the 30ms ISI, CORT treatment selectively disrupted sensorimotor gating of hBDNFVal/Met heterozygote mice but not hBDNFVal/Val or hBDNFMet/Met mice. Analysis of startle reactivity revealed that chronic CORT reduced startle reactivity of hBDNFVal/Val male mice by 51%. However, this was independent of the effect of CORT on PPI. In summary, we provide evidence of a distinct BDNFVal66Met heterozygote-specific phenotype using the sensorimotor gating endophenotype of schizophrenia. These data have important implications for clinical studies where, if possible, the BDNFVal/Met heterozygote genotype should be distinguished from the BDNFMet/Met genotype. PMID- 27262113 TI - Interferon-gamma Production by Peripheral Lymphocytes Predicts Survival of Tumor Bearing Mice Receiving Dual PD-1/CTLA-4 Blockade. AB - Immune checkpoint inhibitors are transforming the way cancer is treated. However, these therapies do not benefit all patients and frequently cause significant immune-related adverse events. Biomarkers that identify patients with a favorable early response to therapy are essential for guiding treatment decisions and improving patient outcomes. In this report of our study, we present evidence that shortly after administration of dual PD-1/CTLA-4 blockade, the proinflammatory capacity of peripheral lymphocytes is predictive of tumor progression and survival outcomes in multiple murine models. Specifically, we observed that the quantity of interferon-gamma (IFNgamma) produced by peripheral lymphocytes in response to CD3/CD28 stimulation was robustly correlated with subsequent survival outcomes. In the tumor models and early time points assessed in this study, this relationship was considerably more predictive than a host of other potential biomarkers, several of which have been previously reported. Overall, these findings suggest that measuring the capacity of peripheral lymphocytes to produce IFNgamma may help identify which patients are benefitting from combination anti PD-1/anti-CTLA-4 immunotherapy. Cancer Immunol Res; 4(8); 650-7. (c)2016 AACR. PMID- 27262115 TI - Utility of graded prognostic assessment in evaluation of patients with brainstem metastases treated with radiosurgery. AB - OBJECTIVES: Prospective data regarding the safety and efficacy of stereotactic radiosurgery (SRS) for patients with metastatic disease involving the brainstem are lacking. The aim of this study was to assess the efficacy and toxicity of SRS for patients with brainstem metastases treated at our institution. PATIENTS AND METHODS: From September 2007 to October 2015, patients treated with SRS for brain metastases were prospectively entered into an institutional database. Forty eight patients with 51 lesions involving the brainstem with clinical follow-up were identified. Local control (LC), elsewhere brain failure (EBF) and overall survival (OS) were assessed from the date of radiosurgery using the Kaplan-Meier method. Univariate and multivariate analyses of factors related to OS were performed using a Cox proportional hazards model. RESULTS: Median clinical follow up was 4.8 months. Median patient age was 62 (range: 28-87); non-small cell lung and breast cancer were the most common primaries at 54% and 21% respectively. Median brainstem lesion volume was 0.12cm(3) (range: 0.01-3.67cm(3)). Whole brain radiotherapy was previously utilized in 19 patients (40%). The median OS was 7.6 months and the 12 month LC rate was 89%. Only 2 patients (4%) experienced grade 3 motor toxicity secondary to SRS. 11 of the 16 patients (69%) initially presenting with symptoms related to brainstem metastases had symptom improvement or resolution following SRS. On multivariate analysis, graded prognostic assessment (GPA) score>2 was predictive of improved survival (p<0.01) while prior chemotherapy use predicted decreased survival (p=0.049). CONCLUSIONS: SRS is associated with high LC rates and low toxicity for brainstem metastases. Improved OS was seen for patients with GPA score>2. GPA appears to be a useful tool for assessing prognosis in patients with brainstem metastases. Small volume lesions were safely treated with or without prior whole brain radiotherapy. PMID- 27262114 TI - Molecular Pathways: Endothelial Cell FAK-A Target for Cancer Treatment. AB - The nonreceptor protein tyrosine kinase, focal adhesion kinase (FAK, also known as PTK2), is a key mediator of signal transduction downstream of integrins and growth factor receptors in a variety of cells, including endothelial cells. FAK is upregulated in several advanced-stage solid tumors and has been described to promote tumor progression and metastasis through effects on both tumor cells and stromal cells. This observation has led to the development of several FAK inhibitors, some of which have entered clinical trials (GSK2256098, VS-4718, VS 6062, VS-6063, and BI853520). Resistance to chemotherapy is a serious limitation of cancer treatment and, until recently, most studies were restricted to tumor cells, excluding the possible roles performed by the tumor microenvironment. A recent report identified endothelial cell FAK (EC-FAK) as a major regulator of chemosensitivity. By dysregulating endothelial cell-derived paracrine (also known as angiocrine) signals, loss of FAK solely in the endothelial cell compartment is able to induce chemosensitization to DNA-damaging therapies in the malignant cell compartment and thereby reduce tumor growth. Herein, we summarize the roles of EC FAK in cancer and development and review the status of FAK-targeting anticancer strategies. Clin Cancer Res; 22(15); 3718-24. (c)2016 AACR. PMID- 27262116 TI - Water quality permitting: From end-of-pipe to operational strategies. AB - End-of-pipe permitting is a widely practised approach to control effluent discharges from wastewater treatment plants. However, the effectiveness of the traditional regulation paradigm is being challenged by increasingly complex environmental issues, ever growing public expectations on water quality and pressures to reduce operational costs and greenhouse gas emissions. To minimise overall environmental impacts from urban wastewater treatment, an operational strategy-based permitting approach is proposed and a four-step decision framework is established: 1) define performance indicators to represent stakeholders' interests, 2) optimise operational strategies of urban wastewater systems in accordance to the indicators, 3) screen high performance solutions, and 4) derive permits of operational strategies of the wastewater treatment plant. Results from a case study show that operational cost, variability of wastewater treatment efficiency and environmental risk can be simultaneously reduced by at least 7%, 70% and 78% respectively using an optimal integrated operational strategy compared to the baseline scenario. However, trade-offs exist between the objectives thus highlighting the need of expansion of the prevailing wastewater management paradigm beyond the narrow focus on effluent water quality of wastewater treatment plants. Rather, systems thinking should be embraced by integrated control of all forms of urban wastewater discharges and coordinated regulation of environmental risk and treatment cost effectiveness. It is also demonstrated through the case study that permitting operational strategies could yield more environmentally protective solutions without entailing more cost than the conventional end-of-pipe permitting approach. The proposed four-step permitting framework builds on the latest computational techniques (e.g. integrated modelling, multi-objective optimisation, visual analytics) to efficiently optimise and interactively identify high performance solutions. It could facilitate transparent decision making on water quality management as stakeholders are involved in the entire process and their interests are explicitly evaluated using quantitative metrics and trade-offs considered in the decision making process. We conclude that the operational strategy-based permitting shows promising for regulators and water service providers alike. PMID- 27262117 TI - Characteristics of meso-particles formed in coagulation process causing irreversible membrane fouling in the coagulation-microfiltration water treatment. AB - In coagulation-membrane filtration water treatment processes, it is still difficult to determine the optimal coagulation condition to minimize irreversible membrane fouling. In microfiltration (MF), meso-particles (i.e., 20 nm-0.5 MUm) are thought to play an important role in irreversible membrane fouling, especially their characteristics of particle number (PN) and zeta potential (ZP). In this study, a new nanoparticle tracker combined a high-output violet laser with a microscope was developed to identify the physicochemical characteristics of these microscopic and widely dispersed meso-particles. The effects of pH and coagulant dose on ZP and PN of micro-particles (i.e., >0.5 MUm) and meso particles were investigated, and then coagulation-MF tests were conducted. As the result, irreversible membrane fouling was best controlled for both types of membranes, while meso-particle ZP approached zero at around pH 5.5 for both types of natural water. Since PN was greatest under these conditions, ZP is more important in determining the extent of irreversible membrane fouling than PN. However, the acidic condition to neutralize meso-particles is not suitable for actual operation, as considering residual aluminum concentration, pipe corrosion, and chlorination efficiency. It is therefore necessary to investigate coagulants or other methods for the appropriate modification of meso-particle characteristics. PMID- 27262118 TI - Autotrophic nitrogen assimilation and carbon capture for microbial protein production by a novel enrichment of hydrogen-oxidizing bacteria. AB - Domestic used water treatment systems are currently predominantly based on conventional resource inefficient treatment processes. While resource recovery is gaining momentum it lacks high value end-products which can be efficiently marketed. Microbial protein production offers a valid and promising alternative by upgrading low value recovered resources into high quality feed and also food. In the present study, we evaluated the potential of hydrogen-oxidizing bacteria to upgrade ammonium and carbon dioxide under autotrophic growth conditions. The enrichment of a generic microbial community and the implementation of different culture conditions (sequenced batch resp. continuous reactor) revealed surprising features. At low selection pressure (i.e. under sequenced batch culture at high solid retention time), a very diverse microbiome with an important presence of predatory Bdellovibrio spp. was observed. The microbial culture which evolved under high rate selection pressure (i.e. dilution rate D = 0.1 h(-1)) under continuous reactor conditions was dominated by Sulfuricurvum spp. and a highly stable and efficient process in terms of N and C uptake, biomass yield and volumetric productivity was attained. Under continuous culture conditions the maximum yield obtained was 0.29 g cell dry weight per gram chemical oxygen demand equivalent of hydrogen, whereas the maximum volumetric loading rate peaked 0.41 g cell dry weight per litre per hour at a protein content of 71%. Finally, the microbial protein produced was of high nutritive quality in terms of essential amino acids content and can be a suitable substitute for conventional feed sources such as fishmeal or soybean meal. PMID- 27262119 TI - Kinetic and microbiological characterization of aerobic granules performing partial nitritation of a low-strength wastewater at 10 degrees C. AB - A granular airlift reactor enriched in ammonia oxidizing bacteria (AOB) was operated at 10 degrees C performing stable partial nitritation in the long-term. The reactor treated a synthetic low-strength influent during 250 days with an average nitrogen loading rate of 0.63 +/- 0.06 g N L(-1) d(-1). Nitrate production was barely detected, being the average concentration in the effluent of 0.6 +/- 0.3 mg N-NO3 L(-1). Furthermore, a suitable effluent for a subsequent reactor performing the anammox process was achieved. A maximum specific growth rate as high as 0.63 +/- 0.05 d(-1) was determined by performing kinetic experiments with the granular sludge in a chemostat and fitting the results to the Monod model. Pyrosequencing analysis showed a high enrichment in AOB (41 and 65% of the population were identified as Nitrosomonas genus on day 98 and 233, respectively) and an effective repression of nitrite oxidizing bacteria in the long-term. Pyrosequencing analysis also identified the coexistence of nitrifying bacteria and heterotrophic psychrotolerant microorganisms in the granular sludge. Some psychrotolerant microorganisms are producers of cryoprotective extracellular polymeric substances that could explain the better survival of the whole consortia at cold temperatures. PMID- 27262120 TI - Pilot-scale UV/H2O2 advanced oxidation process for municipal reuse water: Assessing micropollutant degradation and estrogenic impacts on goldfish (Carassius auratus L.). AB - Low concentrations (ng/L-MUg/L) of emerging micropollutant contaminants in municipal wastewater treatment plant effluents affect the possibility to reuse these waters. Many of those micropollutants elicit endocrine disrupting effects in aquatic organisms resulting in an alteration of the endocrine system. A potential candidate for tertiary municipal wastewater treatment of these micropollutants is ultraviolet (UV)/hydrogen peroxide (H2O2) as an advanced oxidation process (AOP) which was currently applied to treat the secondary effluent of the Gold Bar Wastewater Treatment Plant (GBWWTP) in Edmonton, AB, Canada. A new approach is presented to predict the fluence-based degradation rate constants (kf') of environmentally occurring micropollutants including carbamazepine [(0.87-1.39) * 10(-3) cm(2)/mJ] and 2,4-Dichlorophenoxyacetic acid (2,4-D) [(0.60-0.91) * 10(-3) cm(2)/mJ for 2,4-D] in a medium pressure (MP) UV/H2O2 system based on a previous bench-scale investigation. Rather than using removal rates, this approach can be used to estimate the performance of the MP UV/H2O2 process for degrading trace contaminants of concern found in municipal wastewater. In addition to the ability to track contaminant removal/degradation, evaluation of the MP UV/H2O2 process was also accomplished by identifying critical ecotoxicological endpoints (i.e., estrogenicity) of the treated wastewater. Using quantitative PCR, mRNA levels of estrogen-responsive (ER) genes ERalpha1, ERalpha2, ERbeta1, ERbeta2 and NPR as well as two aromatase encoding genes (CYP19a and CYP19b) in goldfish (Carassius auratus L.) were measured during exposure to the GBWWTP effluent before and after MP UV/H2O2 treatment (a fluence of 1000 mJ/cm(2) and 20 mg/L of H2O2) in spring, summer and fall. Elevated expression of estrogen-responsive genes in goldfish exposed to UV/H2O2 treated effluent (a 7-day exposure) suggested that the UV/H2O2 process may induce acute estrogenic disruption to goldfish principally because of the possible formation of various oxidation by-products. However, prolonged exposure of goldfish (60 days) in UV/H2O2 treated effluent showed a restoration trend of ER gene expressions, especially in the summer. Collectively, our findings provide valuable indications regarding the long-term in vivo assessment of the MP UV/H2O2 process for removing/degrading endocrine disrupting compounds detected in the municipal wastewater effluents. PMID- 27262121 TI - High nutrient concentration and temperature alleviated formation of large colonies of Microcystis: Evidence from field investigations and laboratory experiments. AB - Correlations between Microcystis colony size and environmental factors were investigated in Meiliang Bay and Gonghu Bay of Lake Taihu (China) from 2011 to 2013. Compared with Gonghu Bay, both nutrient concentrations and Microcystis colony sizes were greater in Meiliang Bay. The median colony size (D50: 50% of the total mass of particles smaller than this size) increased from April to August and then decreased until November. In both bays, the average D50 of Microcystis colonies were <100 MUm in spring, but colonies within moderate-size (100-500 MUm) dominated in summer. The differences in colony size in Meiliang Bay and Gonghu Bay were probably due to horizontal drift driven by the prevailing south wind in summer. Redundancy analysis (RDA) of field data indicated that colony size was negatively related to nutrient concentrations but positively related to air temperature, suggesting that low nutrient concentrations and high air temperature promoted formation of large colonies. To validate the field survey, Microcystis colonies collected from Lake Taihu were cultured at different temperatures (15, 20, 25 and 30 degrees C) under high and low nutrient concentrations for 9 days. The size of Microcystis colonies significantly decreased when temperature was above 20 degrees C but had no significant change at 15 degrees C. The differences in temperature effects on colony formation shown from field and laboratory suggested that the larger colonies in summer were probably due to the longer growth period rather than the higher air temperature and light intensity. In addition, colony size decreased more significantly at high nutrient levels. Therefore, it could be concluded that high nutrient concentration and temperature may alleviate formation of large colonies of Microcystis. PMID- 27262122 TI - N-Nitrosamines and halogenated disinfection byproducts in U.S. Full Advanced Treatment trains for potable reuse. AB - Water utilities are increasingly considering indirect and direct potable reuse of municipal wastewater effluents. Disinfection byproducts (DBPs), particularly N nitrosamines, are key contaminants of potential health concern for potable reuse. This study quantified the concentrations of N-nitrosamines and a suite of regulated and unregulated halogenated DBPs across five U.S. potable reuse Full Advanced Treatment trains incorporating microfiltration, reverse osmosis, and UV based advanced oxidation. Low MUg/L concentrations of trihalomethanes, haloacetic acids, dichloroacetonitrile, and dichloroacetamide were detected in the secondary or tertiary wastewater effluents serving as influents to potable reuse treatment trains, while the concentrations of N-nitrosamines were more variable (e.g., <2 320 ng/L for N-nitrosodimethylamine). Ozonation promoted the formation of N nitrosamines, haloacetaldehydes, and haloacetamides, but biological activated carbon effectively reduced concentrations of these DBPs. Application of chloramines upstream of microfiltration for biofouling control increased DBP concentrations to their highest levels observed along the treatment trains. Reverse osmosis rejected DBPs to varying degrees, ranging from low for some (e.g., N-nitrosamines, trihalomethanes, and haloacetonitriles) to high for other DBPs. UV-based advanced oxidation eliminated N-nitrosamines, but only partially removed halogenated DBPs. Chloramination of the treatment train product waters under simulated distribution system conditions formed additional DBPs, with concentrations often equaling or exceeding those in the treatment train influents. Overall, the concentration profiles of DBPs were fairly consistent within individual treatment trains for sampling campaigns separated by months and across different treatment trains for the same sampling time window. Weighting DBP concentrations by their toxic potencies highlighted the potential significance of haloacetonitriles, which were not effectively removed by reverse osmosis and advanced oxidation, to the DBP-associated toxicity in potable reuse waters. PMID- 27262123 TI - Adsorption dynamics of methyl violet onto granulated mesoporous carbon: Facile synthesis and adsorption kinetics. AB - A new and facile one-step synthesis method for preparing granulated mesoporous carbon (GMC) with three-dimensional spherical mesoporous symmetry is prepared to remove large molecular weight organic compounds in aqueous phase. GMC is synthesized in a single step using as-synthesized mesoporous carbon particles and organic binders through a simple and economical synthesis approach involving a simultaneous calcination and carbonization process. Characterization results obtained from SEM, XRD, as well as surface and porosity analysis indicate that the synthesized GMC has similar physical properties to those of the powdered mesoporous carbon and maintains the Brunauer-Emmett-Teller (BET) surface area and pore volume because the new synthesis method prevents the collapse of the pores during the granulation process. Batch adsorption experiments revealed GMC showed a substantial adsorption capacity (202.8 mg/g) for the removal of methyl violet as a target large molecular contaminant in aqueous phase. The mechanisms and dynamics modeling of GMC adsorption were also fully examined, which revealed that surface diffusion was rate limiting step on adsorption process of GMC. Adsorption kinetics of GMC enables 3 times faster than that of granular activated carbon in terms of surface diffusion coefficient. This is the first study, to the best of our knowledge, to synthesize GMC as an adsorbent for water purification by using facile granulation method and to investigate the adsorption kinetics and characteristics of GMC. This study introduces a new and simple method for the synthesis of GMC and reveals its adsorption characteristics for large molecular compounds in a water treatment. PMID- 27262124 TI - Students with autism spectrum disorder in college: Results from a preliminary mixed methods needs analysis. AB - BACKGROUND: There is a growing call for empirically based programming to support the success of students with autism spectrum disorder (ASD) as they transition to college. AIMS: The purpose of this study was to identify the needs and challenges faced by adolescents and young adults with ASD in postsecondary education. METHODS: A mixed methods approach was taken to explore the needs of college-bound and college-enrolled students with ASD. Primary stakeholders (i.e., parents, educators/support staff from secondary and postsecondary institutions, and students) participated in an online survey (n=67) and focus groups (n=15). RESULTS: Across the stakeholder groups, commonly identified areas of difficulty included limited interpersonal competence, managing competing demands in postsecondary education, and poor emotional regulation. There was a high degree of agreement across stakeholders in the identified needs and challenges. IMPLICATIONS: Findings from this preliminary needs analysis will inform the development of programming to support students with ASD. PMID- 27262125 TI - A speech pronunciation practice system for speech-impaired children: A study to measure its success. AB - BACKGROUND: The speech pronunciation practice (SPP) system enables children with speech impairments to practise and improve their speech pronunciation. However, little is known about the surrogate measures of the SPP system. AIMS: This research aims to measure the success and effectiveness of the SPP system using three surrogate measures: usage (frequency of use), performance (recognition accuracy) and satisfaction (children's subjective reactions), and how these measures are aligned with the success of the SPP system, as well as to each other. METHODS AND PROCEDURES: We have measured the absolute change in the word error rate (WER) between the pre- and post-training, using the ANOVA test. Correlation co-efficiency (CC) analysis was conducted to test the relation between the surrogate measures, while a Structural Equation Model (SEM) was used to investigate the causal relations between the measures. OUTCOMES AND RESULTS: The CC test results indicate a positive correlation between the surrogate measures. The SEM supports all the proposed gtheses. The ANOVA results indicate that SPP is effective in reducing the WER of impaired speech. CONCLUSIONS AND IMPLICATIONS: The SPP system is an effective assistive tool, especially for high levels of severity. We found that performance is a mediator of the relation between "usage" and "satisfaction". PMID- 27262127 TI - Receptor-mediated sorting of soluble vacuolar proteins: myths, facts, and a new model. AB - To prevent their being released to the cell exterior, acid hydrolases are recognized by receptors at some point in the secretory pathway and diverted towards the lytic compartment of the cell (lysosome or vacuole). In animal cells, the receptor is called the mannosyl 6-phosphate receptor (MPR) and it binds hydrolase ligands in the trans-Golgi network (TGN). These ligands are then sequestered into clathrin-coated vesicles (CCVs) because of motifs in the cytosolic tail of the MPR which interact first with monomeric adaptors (Golgi localized, Gamma-ear-containing, ARF-binding proteins, GGAs) and then with tetrameric (adaptin) adaptor complexes. The CCVs then fuse with an early endosome, whose more acidic lumen causes the ligands to dissociate. The MPRs are then recycled back to the TGN via retromer-coated carriers. Plants have vacuolar sorting receptors (VSRs) which were originally identified in CCVs isolated from pea (Pisum sativum L.) cotyledons. It was therefore assumed that VSRs would have an analogous function in plants to MPRs in animals. Although this dogma has enjoyed wide support over the last 20 years there are many inconsistencies. Recently, results have been published which are quite contrary to it. It now emerges that VSRs and their ligands can interact very early in the secretory pathway, and dissociate in the TGN, which, in contrast to its mammalian counterpart, has a pH of 5.5. Multivesicular endosomes in plants lack proton pump complexes and consequently have an almost neutral internal pH, which discounts them as organelles of pH-dependent receptor-ligand dissociation. These data force a critical re-evaluation of the role of CCVs at the TGN, especially considering that vacuolar cargo ligands have never been identified in them. We propose that one population of TGN-derived CCVs participate in retrograde transport of VSRs from the TGN. We also present a new model to explain how secretory and vacuolar cargo proteins are effectively separated after entering the late Golgi/TGN compartments. PMID- 27262126 TI - Evolutionary divergence of phytochrome protein function in Zea mays PIF3 signaling. AB - Two maize phytochrome-interacting factor (PIF) basic helix-loop-helix (bHLH) family members, ZmPIF3.1 and ZmPIF3.2, were identified, cloned and expressed in vitro to investigate light-signaling interactions. A phylogenetic analysis of sequences of the maize bHLH transcription factor gene family revealed the extent of the PIF family, and a total of seven predicted PIF-encoding genes were identified from genes encoding bHLH family VIIa/b proteins in the maize genome. To investigate the role of maize PIFs in phytochrome signaling, full-length cDNAs for phytochromes PhyA2, PhyB1, PhyB2 and PhyC1 from maize were cloned and expressed in vitro as chromophorylated holophytochromes. We showed that ZmPIF3.1 and ZmPIF3.2 interact specifically with the Pfr form of maize holophytochrome B1 (ZmphyB1), showing no detectable affinity for the Pr form. Maize holophytochrome B2 (ZmphyB2) showed no detectable binding affinity for PIFs in either Pr or Pfr forms, but phyB Pfr from Arabidopsis interacted with ZmPIF3.1 similarly to ZmphyB1 Pfr. We conclude that subfunctionalization at the protein-protein interaction level has altered the role of phyB2 relative to that of phyB1 in maize. Since the phyB2 mutant shows photomorphogenic defects, we conclude that maize phyB2 is an active photoreceptor, without the binding of PIF3 seen in other phyB family proteins. PMID- 27262128 TI - Prevalence and Correlates of HIV Disclosure Among Children and Adolescents in Low and Middle-Income Countries: A Systematic Review. AB - OBJECTIVE: Disclosure of HIV status among children and adolescents living with HIV has both beneficial and challenging aspects. To address existing knowledge gaps and update the literature on childhood disclosure, we conducted a systematic review on caregivers' perceptions and practices of HIV disclosure in low- and middle-income countries (LMICs). METHODS: Standard databases were searched for studies conducted in LMICs, published in English between 2004 and 2015. Excluded articles were reviews or case reports, and those not reporting childhood disclosure. Data regarding prevalence, correlates and impact of disclosure, were presented as frequencies. RESULTS: Two authors independently screened 982 articles. After applying eligibility criteria, 22 articles representing 12 countries and 2,843 children were reviewed. The proportion of fully disclosed children ranged from 1.7% to 41.0%. Up to 49.5% children were provided "deflected" information (use of a non-HIV-related reason for explaining illness and health care visits). Factors associated with full disclosure included antiretroviral treatment initiation and caregivers' felt need for maintaining optimal adherence. Barriers to disclosure included fear of negative psychological reactions and inadvertent disclosure to others. Caregivers perceived a strong need for active participation from health care providers to aid the process of disclosure. CONCLUSIONS: Full disclosure of HIV status was not common among children and adolescents in LMICs, while the practice of deflected disclosure was prominent. Caregivers perceived the need for support from health care providers during the disclosure process. Evidence-based guidelines incorporating the developmental status of the child, locally prevalent cultures, and caregiver perceptions are prerequisite to enhancing disclosure in these settings. PMID- 27262129 TI - Bioaccumulation and metabolomics responses in oysters Crassostrea hongkongensis impacted by different levels of metal pollution. AB - Jiulong River Estuary, located in southern China, was heavily contaminated by metal pollution. In this study, the estuarine oysters Crassostrea hongkongensis were transplanted to two sites with similar hydrological conditions but different levels of metal pollution in Jiulong River Estuary over a six-month period. We characterized the time-series change of metal bioaccumulation and final metabolomics responses of oysters. Following transplantation, all metals (Cd, Cu, Cr, Ni, Pb, and Zn) in the oyster digestive glands had elevated concentrations over time. By the end of six-month exposure, Cu, Zn and Cd were the main metals significantly differentiating the two sites. Using (1)H NMR metabolite approach, we further demonstrated the disturbance in osmotic regulation, energy metabolism, and glycerophospholipid metabolism induced by metal contaminations. Six months later, the oysters transplanted in the two sites showed a similar metabolite variation pattern when compared with the initial oysters regardless of different metal levels in the tissues. Interestingly, by comparing the oysters from two sites, the more severely polluted oysters accumulated significantly higher amounts of osmolytes (betaine and homarine) and lower energy storage compounds (glycogen) than the less polluted oysters; these changes could be the potential biomarkers for different levels of metal pollution. Our study demonstrated the complexity of biological effects under field conditions, and NMR metabolomics provides an important approach to detect sensitive variation of oyster inner status. PMID- 27262130 TI - Environmentally relevant impacts of nano-TiO2 on abiotic degradation of bisphenol A under sunlight irradiation. AB - Understanding the effects of nano-TiO2 particles on the environmental behaviors of organic pollutants in natural aquatic environments is of paramount importance considering that large amount of nano-TiO2 is being released in the environment. In this study, the effect of nano-TiO2 on the degradation of bisphenol A (BPA) in water was investigated under simulated solar light irradiation. The results indicated that nano-TiO2 at environmentally relevant concentration (1 mg/L) could significantly facilitate the abiotic degradation of BPA (also at low concentration) under mild solar light irradiation, with the pseudo first-order rate constant (kobs) for BPA degradation raised by 1-2 orders of magnitude. As reflected by the inhibition experiments, hydroxyl radicals (OHs) and superoxide radical species were the predominant active species responsible for BPA degradation. The reaction was affected by water pH, and the degradation rate was higher at acidic or alkaline conditions than that at neutral condition. Humic acid (HA) also affected the reaction rate, depending on its concentration. At lower concentration (the mass ratio of HA/nano-TiO2 was 0.1:1), HA improved the dispersion and stability of nano-TiO2 in aquatic environment. As a result, the yield of OHs by nano-TiO2 under sunlight irradiation increased and BPA degradation was facilitated. When the HA concentration increased, a coating of HA formed on the surface of nano-TiO2. Although nano-TiO2 became more stable, the light absorption by nano-TiO2 was significantly reduced due to the strong light absorption of the HA coated on the surface. As a consequence, the yield of OH decreased and BPA degradation was depressed. The results imply that nano-TiO2 at low concentration may distinctly mediate BPA degradation, and can contribute to the natural attenuation of some organic pollutants in aquatic environment with low level of HA. However, this process would be significantly reduced in the presence of high level of HA. PMID- 27262131 TI - Levoglucosan evidence for biomass burning records over Tibetan glaciers. AB - Intense biomass burning (BB) events are widespread in tropical and subtropical Asia. However, the impact of BB aerosols on the Tibetan Plateau (TP), especially on Tibetan glaciers, is poorly understood. In this study, BB signals are revealed using the specific molecular tracer levoglucosan in snow and ice samples from different Tibetan glaciers. Tibetan glaciers mainly act as receptors of BB emissions from surrounding regions. Significant differences in levoglucosan concentrations in glacier samples collected from two slopes on the same mountain range indicate that high mountains can act as natural barriers to block the transport of smoke aerosols to the TP. Levoglucosan concentrations show a decreasing trend from west to east on glaciers impacted by the Indian summer monsoon on the southern edge of the TP, while the opposite pattern was observed on glaciers under the prevailing westerlies along the northern edge. The emission sources, the controlling climate system, as well as deposition and degradation during transport determined the spatial distribution regimes of levoglucosan concentration on Tibetan glaciers. PMID- 27262132 TI - Gas flaring and resultant air pollution: A review focusing on black carbon. AB - Gas flaring is a prominent source of VOCs, CO, CO2, SO2, PAH, NOX and soot (black carbon), all of which are important pollutants which interact, directly and indirectly, in the Earth's climatic processes. Globally, over 130 billion cubic metres of gas are flared annually. We review the contribution of gas flaring to air pollution on local, regional and global scales, with special emphasis on black carbon (BC, "soot"). The temporal and spatial characteristics of gas flaring distinguishes it from mobile combustion sources (transport), while the open-flame nature of gas flaring distinguishes it from industrial point-sources; the high temperature, flame control, and spatial compactness distinguishes gas flaring from both biomass burning and domestic fuel-use. All of these distinguishing factors influence the quantity and characteristics of BC production from gas flaring, so that it is important to consider this source separately in emissions inventories and environmental field studies. Estimate of the yield of pollutants from gas flaring have, to date, paid little or no attention to the emission of BC with the assumption often being made that flaring produces a smokeless flame. In gas flares, soot yield is known to depend on a number of factors, and there is a need to develop emission estimates and modelling frameworks that take these factors into consideration. Hence, emission inventories, especially of the soot yield from gas flaring should give adequate consideration to the variation of fuel gas composition, and to combustion characteristics, which are strong determinants of the nature and quantity of pollutants emitted. The buoyant nature of gas flaring plume, often at temperatures in the range of 2000 K, coupled with the height of the stack enables some of the pollutants to escape further into the free troposphere aiding their long-range transport, which is often not well-captured by model studies. PMID- 27262133 TI - Effects of Lumbriculus variegatus (Annelida, Oligochaete) bioturbation on zinc sediment chemistry and toxicity to the epi-benthic invertebrate Chironomus tepperi (Diptera: Chironomidae). AB - Classical laboratory-based single-species sediment bioassays do not account for modifications to toxicity from bioturbation by benthic organisms which may impact predictions of contaminated sediment risk to biota in the field. This study aims to determine the effects of bioturbation on the toxicity of zinc measured in a standard laboratory bioassay conducted with chironomid larvae (Chironomus tepperi). The epi-benthic chironomid larvae were exposed to two different levels of sediment contamination (1600 and 1980 mg/kg of dry weight zinc) in the presence or absence of annelid worms (Lumbriculus variegatus) which are known to be tolerant to metal and to have a large impact on sediment properties through bioturbation. Chironomids had 5-6x higher survival in the presence of L. variegatus which shows that bioturbation had a beneficial effect on the chironomid larvae. Chemical analyses showed that bioturbation induced a flux of zinc from the pore water into the water column, thereby reducing the bioavailability of zinc in pore water to the chironomid larvae. This also suggested that pore water was the major exposure path for the chironomids to metals in sediment. During the study, annelid worms (Oligochaetes) produced a thin layer of faecal pellets at the sediment surface, a process known to: (i) create additional adsorption sites for zinc, thus reducing its availability, (ii) increase the microbial abundance that in turn could represent an additional food source for opportunistic C. tepperi larvae, and (iii) modify the microbial community's structure and alter the biogeochemical processes it governs thus indirectly impact zinc toxicity. This study represents a contribution in recognising bioturbating organisms as "ecological engineers" as they directly and indirectly influence metal bioavailability and impact other sediment-inhabiting species. This is significant and should be considered in risk assessment of zinc levels (and other metals) in contaminated sediment when extrapolating from laboratory studies to the field. PMID- 27262134 TI - Is standard deviation of daily PM2.5 concentration associated with respiratory mortality? AB - Studies on health effects of air pollution often use daily mean concentration to estimate exposure while ignoring daily variations. This study examined the health effects of daily variation of PM2.5. We calculated daily mean and standard deviations of PM2.5 in Hong Kong between 1998 and 2011. We used a generalized additive model to estimate the association between respiratory mortality and daily mean and variation of PM2.5, as well as their interaction. We controlled for potential confounders, including temporal trends, day of the week, meteorological factors, and gaseous air pollutants. Both daily mean and standard deviation of PM2.5 were significantly associated with mortalities from overall respiratory diseases and pneumonia. Each 10 MUg/m(3) increment in daily mean concentration at lag 2 day was associated with a 0.61% (95% CI: 0.19%, 1.03%) increase in overall respiratory mortality and a 0.67% (95% CI: 0.14%, 1.21%) increase in pneumonia mortality. And a 10 MUg/m(3) increase in standard deviation at lag 1 day corresponded to a 1.40% (95% CI: 0.35%, 2.46%) increase in overall respiratory mortality, and a 1.80% (95% CI: 0.46%, 3.16%) increase in pneumonia mortality. We also observed a positive but non-significant synergistic interaction between daily mean and variation on respiratory mortality and pneumonia mortality. However, we did not find any significant association with mortality from chronic obstructive pulmonary diseases. Our study suggests that, besides mean concentration, the standard deviation of PM2.5 might be one potential predictor of respiratory mortality in Hong Kong, and should be considered when assessing the respiratory effects of PM2.5. PMID- 27262135 TI - Influence of repetitive peripheral magnetic stimulation on neural plasticity in the motor cortex related to swallowing. AB - The aim of this study was to evaluate the effect of repetitive peripheral magnetic stimulation at two different frequencies (20 and 30 Hz) on cortical excitability in motor areas related to swallowing in healthy individuals. The study participants were 10 healthy normal volunteers (two women and eight men, age range 25-36 years). Repetitive peripheral magnetic stimulation was applied to the submandibular muscle using a parabolic coil at the site where contraction of the suprahyoid muscles was elicited. Stimulation was continued for 10 min (total 1200 pulses) at 20 Hz on 1 day and at 30 Hz on another day, with the stimulation strength set at 90% of the intensity that elicited pain. The motor-evoked potential amplitude of suprahyoid muscles was assessed before, immediately after, and 30 min after stimulation. Stimulations at both 20 and 30 Hz significantly increased motor-evoked potential amplitude (P<0.05), with the increase maintained until 30 min after stimulation. The motor-evoked potential amplitude immediately after stimulation was not significantly different between the 20 and 30 Hz frequencies. The results indicated that repetitive magnetic stimulation increased motor-evoked potential amplitude of swallowing muscles, suggesting facilitation of the motor cortex related to swallowing in healthy individuals. PMID- 27262136 TI - Measuring functioning and disability after a disaster: results from the typhoon Haiyan/Yolanda-affected areas of the Philippines. AB - The most commonly reported data after natural disasters are the number of deceased and displaced and the structural and economic damage, whereas disability data are often lacking. Our study assessed disability among the survivors of the Haiyan/Yolanda typhoon that struck Philippines in 2013 and is aimed to identify which context-level variables are associated with higher disability. We used a cross-sectional design and administered a household questionnaire, an individual sociodemographic questionnaire, and the WHODAS 2.0 to 1982 adults. Logistic regression analysis was carried out to address the degree to which demographic variables, effects of the typhoon, individual health state, and rural or urban residence were associated with higher disability. Those aged above 65, employed individuals, students, those not living in their households, and those with one or more health condition or rating their own as health moderate or very poor had higher likelihood of having severe disability. Survivors living in rural contexts and those who received tools/materials to repair their houses were less likely to have higher disability. This study outlines that disability can and should be used as an indicator in surveys after emergencies to identify the most vulnerable groups, thus guiding policies, reconstruction strategies, and health and social interventions. PMID- 27262137 TI - Reproducibility and Inter-rater Reliability of 2 Paediatric Nutritional Screening Tools. AB - OBJECTIVES: The aim of the present study was to assess reproducibility and inter rater reliability of 2 nutritional screening tools (NST): Screening Tool for Risk on Nutritional Status and Growth (STRONGkids) and Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP). METHODS: Prospective observational multicentre study. Patients ages 1 month or older admitted to paediatric or surgical wards were tested within 24 hours of admission by 2 independent observers: experts specialized in paediatric nutrition (physicians or dieticians) and clinical staff nonexpert in nutrition. Diagnosis on admission, underlying diseases, and length of stay were registered. STATISTICAL ANALYSIS: Kappa index (kappa) to evaluate agreement between observers. RESULTS: A total of 223 patients were included (53.4% boys), with mean age of 5.59 (95% confidence interval 4.94-6.22) years. Experts classified 9.9% of patients at high risk with STRONGkids and 19.7% using STAMP, whereas nonexpert staff assigned 6.7% of patients to the high-risk category with STRONGkids and 21.9% with STAMP. Agreement between expert and nonexpert staff was good: 94.78% for STRONGkids (kappa 0.72 [P < 0.001]); 92.55% for STAMP (kappa 0.74 [P < 0.001]). The rate of malnutrition was significantly higher among high-risk patients with both NST, independent of examiner experience. After adjusting for age, both STRONGkids and STAMP high-risk scores predicted longer length of stay, whether assessed by experts or nonexperts, although differences were higher with STRONGkids. CONCLUSIONS: Agreement between experts and nonexpert staff in nutrition was good, producing a similar high-risk patient profile. Our results demonstrate that these NSTs are appropriate for nutritional screening in settings in which users have no previous experience in the field. PMID- 27262139 TI - Novel imaging in renal cell carcinoma. AB - PURPOSE OF REVIEW: Renal cell carcinoma is a heterogeneous disease with a spectrum of subtypes and clinical behavior. Quantitative and qualitative imaging biomarkers are sought to correlate with genetic and histologic features and complement pathologic analysis. RECENT FINDINGS: Texture analysis, radiogenomics, and modality-specific advancements have yielded an array of renal cell carcinoma imaging biomarkers in the research domain. Although many techniques are promising, standardization and validation of these procedures are needed prior to implementation into clinical practice. SUMMARY: We introduce novel imaging techniques and analytic methods which have been shown to contribute to characterization of renal cell carcinoma and its subtypes, aggressiveness, and responsiveness to therapy, including associated advantages and limitations. PMID- 27262138 TI - Beyond prostate-specific antigen: utilizing novel strategies to screen men for prostate cancer. AB - PURPOSE OF REVIEW: The purpose of this article is to review blood and urine tests that are currently available and under investigation for a role in prostate cancer screening and detection. RECENT FINDINGS: Compared with total prostate specific antigen (PSA) alone, its combination with percentage free-to-total PSA contributes greater specificity for prostate cancer, and is a component of two newer blood tests called the 4kScore and Prostate Health Index. All three tests improve the prediction of high-grade disease and are commercially available options to aid in initial or repeat prostate biopsy decisions. PCA3 is a urinary marker that is currently available for repeat prostate biopsy decisions. Although PCA3 alone has inferior prediction of clinically significant disease and requires collection of urine after digital rectal examination, it may be combined with other clinical variables or other urine markers like TMPRSS2:ERG to improve performance. Little data are available to support a role for single nucleotide polymorphisms or other investigational markers in early detection. SUMMARY: Several commercially available blood and urine tests have been shown to improve specificity of PSA for high-grade prostate cancer. Use of such tests would decrease unnecessary biopsy and overdiagnosis of indolent disease. Biopsy of men with moderately elevated PSA without use of such a reflex test should be discouraged. PMID- 27262140 TI - Lymph node dissection for renal cell carcinoma: what are we missing? AB - PURPOSE OF REVIEW: The role of lymph node dissection (LND) is uncertain for patients diagnosed with renal cell carcinoma (RCC). The aim of the current review is to discuss the available literature considering the role and the impact of LND in RCC patients elected for surgical treatment. Controversies, uncertainties as well as outstanding research questions were assessed. RECENT FINDINGS: Anatomical and biological peculiarities of RCC make difficult to localize a sentinel lymph node. Cross-sectional imaging as well as preoperative risk score showed limited applicability in determining which patients may benefit from LND. In patients with larger tumors, locally advanced disease or in the presence of unfavorable characteristics (e.g., lymphadenopathy, high grade, tumor necrosis, and sarcomatoid features), LND has a role mainly for staging purposes. In this specific scenario, a potential effect on the natural history of the disease has been suggested, as well. Salvage LND has been increasingly considered, although no definitive recommendation can be nowadays provided. SUMMARY: The assessment of the role and the effect of LND in RCC is still affected by the presence of limited and flawed data available. Further efforts in terms of basic, translational, and imaging research are urgently needed. PMID- 27262141 TI - Update on active surveillance for clinical T1 renal tumors. AB - PURPOSE OF REVIEW: The purpose is to discuss current data on the utilization and outcomes of active surveillance for T1a renal masses. Specifically, to address which patients are optimal for active surveillance and how their outcomes differ from those undergoing immediate treatment. RECENT FINDINGS: Although nephron sparing surgery is the standard of care for small renal masses (SRMs), active surveillance is becoming a more popular intervention given the results of prospective studies revealing active surveillance to be safe and have excellent cancer-specific survival with intermediate follow-up. Older and sicker patients have competing risk of death from other causes when diagnosed with a SRM. SUMMARY: Active surveillance is becoming a more popular treatment modality for SRMs given the increasing number of incidental diagnoses and better understanding of their often indolent course. Active surveillance with delayed intervention is a well-tolerated treatment modality and appears to have the most benefit for those patients that are older with more comorbidities. PMID- 27262142 TI - Diagnosis and management of spermatic cord tumors. AB - PURPOSE OF REVIEW: Spermatic cord tumors (SCT) are very rare. The present review discusses the most recent literature regarding clinical presentation, pathological characteristics, diagnosis, and management of SCT. RECENT FINDINGS: Although the majority of SCT are benign, when malignant almost all SCT are sarcomas. Liposarcomas are the most common; whereas rhabdomyosarcomas recorded the highest tendency of develop distant metastases. The clinical presentation is usually a unilateral solid slow-growing mass at the level of the inguinal canal and of the scrotum. Surgical excision represents the most common used treatment, and considering the risk in developing local recurrence, radical inguinal orchiectomy and resection of the tumor with negative microscopic surgical margins is mandatory. Adjuvant therapies such as radiotherapy and chemotherapy have been suggested in selected patients, but clear data to demonstrate any improvement in survival are not available. SUMMARY: SCT are rare tumors with high risk of misdiagnosis or mistreatment. The majority are benign, but when malignant almost all are sarcomas. A surgical excision is the treatment of choice; however, no clear data exists documenting the efficacy of a multimodal treatment in reducing high local recurrence rates after surgery. PMID- 27262143 TI - Novel immunotherapeutic strategies to target alloantibody-producing B and plasma cells in transplantation. AB - PURPOSE OF REVIEW: There is an unmet need for immunotherapeutic agents that target humoral alloimmunity in solid organ transplantation. This includes sensitized patients with preformed donor-specific human leucocyte antigen antibodies and patients who develop de-novo donor-specific antibodies, both of which are associated with acute and chronic antibody-mediated rejection and allograft loss. RECENT FINDINGS: In this review, we discuss recent progress in the generation of B-cell and plasma cell-targeted therapeutics, with an emphasis on novel agents. To deplete or inhibit B cells, B-cell-specific mAbs have been developed, including CD20, CD22, CD19 and bi-specific antibodies that target two B-cell antigens. In addition, inhibition of B-cell-activating cytokines, such as B cell-activating factor, may also reduce allo-B-cell activation. Plasma cells remain a difficult therapeutic target, but inhibition of germinal centre responses via costimulatory blockade or IL21 neutralization, induction of plasma cell apoptosis using proteasome inhibitors or disruption of the plasma cell niche are potential avenues being explored. SUMMARY: The ultimate aim of these animal and human studies is to develop agents that efficiently target humoral effectors, whilst sparing B and plasma cells with a regulatory capacity to promote long-term allograft survival, but we remain some distance away from this goal. PMID- 27262144 TI - Invasive Ocular Surface Squamous Neoplasia Masquerading as Nodular Scleritis. AB - The authors report a rare case of ocular surface squamous neoplasia with intraocular involvement that had an initial masquerade presentation of recurrent anterior nodular scleritis. A 35-year-old male patient presented with right eye recurrent anterior nodular scleritis for which a lamellar patch graft was done. Two months later, the patient presented with recurrence of symptoms. Histopathology review revealed the presence of well-differentiated squamous cell malignancy. A high index of suspicion for malignancy is required in such cases when they do not respond to conventional therapy. PMID- 27262145 TI - Automated Quantitative Plaque Analysis for Discrimination of Coronary Chronic Total Occlusion and Subtotal Occlusion in Computed Tomography Angiography. AB - PURPOSE: The aim of this study was to evaluate the utility of automated plaque analysis in differentiating chronic total occlusion (CTO) from subtotal occlusion (SO) in patients with ambiguous coronary lesions on coronary computed tomography angiography (CTA). MATERIALS AND METHODS: A total of 63 patients with 63 ambiguous coronary lesions on CTA were included. The lesion length (LL), diameter stenosis, plaque volume and composition, remodeling index, and contrast density difference (CDD) (reflecting intraluminal contrast kinetics over the lesion) were assessed using an automatic software tool. All patients underwent invasive coronary angiography. RESULTS: Coronary angiography confirmed 28 CTOs and 35 SOs. CTOs showed significantly longer LL (6.4+/-12.3 vs. 1.0+/-2.2 mm, P=0.03) and higher CDD (74%+/-31% vs. 55%+/-32%, P=0.02) compared with SO. The optimal thresholds for prediction of CTO for CDD and LL were >=43% and >=1 mm, respectively (max. sensitivity: 82% for CDD, max. specificity: 77% for LL). The guidewire manipulation time correlated with LL (r=0.529, P=0.004) and CDD (r=0.435, P=0.021) in lesions attempted by percutaneous coronary intervention. CONCLUSIONS: Automated computed tomography plaque analysis may be applied as a noninvasive tool to differentiate CTO from SO. PMID- 27262146 TI - Automated Quantitative Computed Tomography Versus Visual Computed Tomography Scoring in Idiopathic Pulmonary Fibrosis: Validation Against Pulmonary Function. AB - PURPOSE: The aim of the study was to determine whether a novel computed tomography (CT) postprocessing software technique (CALIPER) is superior to visual CT scoring as judged by functional correlations in idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: A total of 283 consecutive patients with IPF had CT parenchymal patterns evaluated quantitatively with CALIPER and by visual scoring. These 2 techniques were evaluated against: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), carbon monoxide transfer coefficient (Kco), and a composite physiological index (CPI), with regard to extent of interstitial lung disease (ILD), extent of emphysema, and pulmonary vascular abnormalities. RESULTS: CALIPER-derived estimates of ILD extent demonstrated stronger univariate correlations than visual scores for most pulmonary function tests (PFTs): (FEV1: CALIPER R=0.29, visual R=0.18; FVC: CALIPER R=0.41, visual R=0.27; DLco: CALIPER R=0.31, visual R=0.35; CPI: CALIPER R=0.48, visual R=0.44). Correlations between CT measures of emphysema extent and PFTs were weak and did not differ significantly between CALIPER and visual scoring. Intriguingly, the pulmonary vessel volume provided similar correlations to total ILD extent scored by CALIPER for FVC, DLco, and CPI (FVC: R=0.45; DLco: R=0.34; CPI: R=0.53). CONCLUSIONS: CALIPER was superior to visual scoring as validated by functional correlations with PFTs. The pulmonary vessel volume, a novel CALIPER CT parameter with no visual scoring equivalent, has the potential to be a CT feature in the assessment of patients with IPF and requires further exploration. PMID- 27262147 TI - The nonmotor features of Parkinson's disease: pathophysiology and management advances. AB - PURPOSE OF REVIEW: In recent years progress has been made in the detection and evaluation of nonmotor symptoms in Parkinson's disease. The pathophysiology is better understood and new treatment is available, which will be discussed in this review. RECENT FINDINGS: The most intriguing recent finding is the fact that Parkinson's disease may be a spreading disease. From the environment a toxin, bacteria, or virus may start in genetically susceptible patients a cascade of alpha-synuclein aggregation which reaches via the olfactory and the enteric system of the gut the brain where further spreading causes symptoms, such as sleep disturbances, motor impairment, and neuropsychiatric symptoms. New treatment should address the abnormal alpha-synuclein folding. If this would be achieved premotor signs, such as hyposmia, rapid eye movement-sleep behavior disorder, constipation, or depression may be a kind of biomarkers which allow together with other diagnostic tools, such as parenchymal sonography, iodobenzamide-scintigraphy and dopamine transporter scans the prediction whether somebody might be under way to develop the full-blown Parkinson's disease syndrome. SUMMARY: Parkinson's disease seems to be a spreading disease which causes not only a dopaminergic deficit as major cause for the movement disorder but also impairs function of many other brain centers which leads to a multitransmitter malfunction. PMID- 27262150 TI - Articles I Would Like to See in JCEHP. PMID- 27262149 TI - Stiff person syndrome and other immune-mediated movement disorders - new insights. AB - PURPOSE OF REVIEW: This review highlights the recent developments in immune mediated movement disorders and how they reflect on clinical practice and our understanding of the underlying pathophysiological mechanisms. RECENT FINDINGS: The antibody spectrum associated with stiff person syndrome and related disorders (SPSD) has broadened and, apart from the classic glutamic acid decarboxylase (GAD)- and amphiphysin-antibodies, includes now also antibodies against dipeptidyl-peptidase-like protein-6 (DPPX), gamma-aminobutyric acid type A receptor (GABAAR), glycine receptor (GlyR) and glycine transporter 2 (GlyT2). The field of movement disorders with neuronal antibodies keeps expanding with the discovery for example of antibodies against leucine rich glioma inactivated protein 1 (LGI1) and contactin associated protein 2 (Caspr2) in chorea, or antibodies targeting ARHGAP26- or Na/K ATPase alpha 3 subunit (ATP1A3) in cerebellar ataxia. Moreover, neuronal antibodies may partly account for movement disorders attributed for example to Sydenham's chorea, coeliac disease, or steroid responsive encephalopathy with thyroid antibodies. Lastly, there is an interface of immunology, genetics and neurodegeneration, e.g. in Aicardi Goutieres syndrome or the tauopathy with IgLON5-antibodies. SUMMARY: Clinicians should be aware of new antibodies such as dipeptidyl-peptidase-like protein-6, gamma-aminobutyric acid type A receptor and glycine transporter 2 in stiff person syndrome and related disorders, as well as of the expanding spectrum of immune mediated movement disorders. PMID- 27262148 TI - Four-dimensional MRI flow examinations in cerebral and extracerebral vessels - ready for clinical routine? AB - PURPOSE OF REVIEW: To evaluate the feasibility of 4-dimensional (4D) flow MRI for the clinical assessment of cerebral and extracerebral vascular hemodynamics in patients with neurovascular disease. RECENT FINDINGS: 4D flow MRI has been applied in multiple studies to qualitatively and quantitatively study intracranial aneurysm blood flow for potential risk stratification and to assess treatment efficacy of various neurovascular lesions, including intraaneurysmal and parent artery blood flow after flow diverter stent placement and staged embolizations of arteriovenous malformations and vein of Galen aneurysmal malformations. Recently, the technique has been utilized to characterize age related changes of normal cerebral hemodynamics in healthy individuals over a broad age range. SUMMARY: 4D flow MRI is a useful tool for the noninvasive, volumetric and quantitative hemodynamic assessment of neurovascular disease without the need for gadolinium contrast agents. Further improvements are warranted to overcome technical limitations before broader clinical implementation. Current developments, such as advanced acceleration techniques (parallel imaging and compressed sensing) for faster data acquisition, dual or multiple velocity encoding strategies for more accurate arterial and venous flow quantification, ultrahigh-field strengths to achieve higher spatial resolution and streamlined postprocessing workflow for more efficient and standardized flow analysis, are promising advancements in 4D flow MRI. PMID- 27262151 TI - Improving Health Care Providers' Capacity for Self-Regulated Learning in Online Continuing Pharmacy Education: The Role of Internet Self-Efficacy. AB - INTRODUCTION: Although Internet-based learning is widely used to improve health professionals' knowledge and skills, the self-regulated learning (SRL) activities of online continuing education in pharmacy are seldom discussed. The main purpose of this study was to explore the relationships between pharmacists' Internet self efficacy (ISE) and their SRL in online continuing education. METHODS: A total of 164 in-service pharmacists in Taiwan were surveyed with the Internet Self Efficacy Survey, including basic ISE (B-ISE), advanced ISE (A-ISE) and professional ISE (P-ISE), as well as the Self-Regulated Learning Questionnaire consisting of preparatory SRL (P-SRL) and enactment SRL (E-SRL). RESULTS: Results of a 1-by-3 (educational levels: junior college versus bachelor versus master) analysis of variance and a 1-by-4 (institutions: community-based versus hospital versus clinic versus company) analysis of variance revealed that there were differences in ISE and SRL among different education levels and working institutions. The hierarchical regression analyses indicated that B-ISE and P-ISE were significant predictors of P-SRL, whereas P-ISE was a critical predictor of E SRL. Moreover, the interaction of P-ISE * age was linked to E-SRL, implying that P-ISE has a stronger influence on E-SRL for older pharmacists than for younger pharmacists. However, the interactions between age and ISE (A-ISE, B-ISE, and P ISE) were not related to P-SRL. DISCUSSION: This study highlighted the importance of ISE and age for increasing pharmacists' SRL in online continuing education. PMID- 27262152 TI - Effectiveness of an Evidence-Based Quality Improvement Approach to Cultural Competence Training: The Veterans Affairs' "Caring for Women Veterans" Program. AB - INTRODUCTION: Although providing culturally sensitive health care is vitally important, there is little consensus regarding the most effective strategy for implementing cultural competence trainings in the health care setting. Evidence based quality improvement (EBQI), which involves adapting evidence-based practices to meet local needs, may improve uptake and effectiveness of a variety of health care innovations. Yet, to our knowledge, EBQI has not yet been applied to cultural competence training. To evaluate whether EBQI could enhance the impact of an evidence-based training intended to improve veterans affairs health care staff gender sensitivity and knowledge (Caring for Women Veterans; CWV), we compared the reach and effectiveness of EBQI delivery versus standard web-based implementation strategies of CWV and assessed barriers and facilitators to EBQI implementation. METHODS: Workgroups at four diverse veterans affairs health care sites were randomized to either an EBQI or standard web-based implementation condition (SI). All EBQI sites selected a group-based implementation strategy. Employees (N = 84) completed pretraining and posttraining assessments of gender sensitivity and knowledge, and focus groups/interviews were conducted with leadership and staff before and after implementation. RESULTS: Reach of CWV was greater in the EBQI condition versus the SI condition. Whereas both gender sensitivity and knowledge improved in the EBQI condition, only gender sensitivity improved in the SI condition. Qualitative analyses revealed that the EBQI approach was well received, although a number of barriers were identified. DISCUSSION: Findings suggest that EBQI can enhance the uptake and effectiveness of employee trainings. However, the decision to pursue EBQI must be informed by a consideration of available resources. PMID- 27262153 TI - Dissemination of Evidence From Systematic Reviews Through Academic CME Providers: A Feasibility Study. AB - INTRODUCTION: Although systematic reviews represent a source of best evidence to support clinical decision-making, reviews are underutilized by clinicians. Barriers include lack of awareness, familiarity, and access. Efforts to promote utilization have focused on reaching practicing clinicians, leaving unexplored the roles of continuing medical education (CME) directors and faculty in promoting systematic review use. This study explored the feasibility of working with CME directors and faculty for that purpose. METHODS: A convenience sample of five academic CME directors and faculty agreed to participate in a feasibility study exploring use in CME courses of systematic reviews from the Agency for Healthcare Research and Quality (AHRQ-SRs). AHRQ-SR topics addressed the comparative effectiveness of health care options. Participants received access to AHRQ-SR reports, associated summary products, and instructional resources. The feasibility study used mixed methods to assess 1) implementation of courses incorporating SR evidence, 2) identification of facilitators and barriers to integration, and 3) acceptability to CME directors, faculty, and learners. RESULTS: Faculty implemented 14 CME courses of varying formats serving 1700 learners in urban, suburban, and rural settings. Facilitators included credibility, conciseness of messages, and availability of supporting materials; potential barriers included faculty unfamiliarity with SRs, challenges in maintaining review currency, and review scope. SR evidence and summary products proved acceptable to CME directors, course faculty, and learners by multiple measures. DISCUSSION: This study demonstrates the feasibility of approaches to use AHRQ-SRs in CME courses/programming. Further research is needed to demonstrate generalizability to other types of CME providers and other systemic reviews. PMID- 27262154 TI - Value of General Medical Knowledge Examinations in Performance Assessment of Practicing Physicians With Potential Competence and Performance Deficiencies. AB - INTRODUCTION: Problems with a physician's performance may arise at any point during their career. As such, there is a need for effective, valid tools and processes to accurately assess and identify deficiencies in competence or performance. Although scores on multiple-choice questions have been shown to be predictive of some aspects of physician performance in practicing physicians, their relationship to overall clinical competence is somewhat uncertain particularly after the first 10 years of practice. As such, the purpose of this study was to examine how a general medical knowledge multiple-choice question examination is associated with a comprehensive assessment of competence and performance in experienced practicing physicians with potential competence and performance deficiencies. METHODS: The study included 233 physicians, of varying specialties, assessed by the University of California, San Diego Physician Assessment and Clinical Education Program (PACE), between 2008 and 2012, who completed the Post-Licensure Assessment System Mechanisms of Disease (MoD) examination. Logistic regression determined if the examination score significantly predicted passing assessment outcome after correcting for gender, international medical graduate status, certification status, and age. RESULTS: Most physicians (89.7%) received an overall passing assessment outcome on the PACE assessment. The mean MoD score was 66.9% correct, with a median of 68.0%. Logistic regression (P = .038) was significant in indicating that physicians with higher MoD examination scores had an increased likelihood of achieving a passing assessment outcome (odds ratio = 1.057). DISCUSSION: Physician MoD scores are significant predictors of overall physician competence and performance as evaluated by PACE assessment. PMID- 27262155 TI - Performance of Certification and Recertification Examinees on Multiple Choice Test Items: Does Physician Age Have an Impact? AB - INTRODUCTION: The development of recertification programs (now referred to as Maintenance of Certification or MOC) by the members of the American Board of Medical Specialties provides the opportunity to study knowledge base across the professional lifespan of physicians. Research results to date are mixed with some studies finding negative associations between age and various measures of competency and others finding no or minimal relationships. METHODS: Four groups of multiple choice test items that were independently developed for certification and MOC examinations in psychiatry and neurology were administered to certification and MOC examinees within each specialty. Percent correct scores were calculated for each examinee. Differences between certification and MOC examinees were compared using unpaired t tests, and logistic regression was used to compare MOC and certification examinee performance on the common test items. RESULTS: Except for the neurology certification test items that addressed basic neurology concepts, the performance of the certification and MOC examinees was similar. The differences in performance on individual test items did not consistently favor one group or the other and could not be attributed to any distinguishable content or format characteristics of those items. DISCUSSION: The findings of this study are encouraging in that physicians who had recently completed residency training possessed clinical knowledge that was comparable to that of experienced physicians, and the experienced physicians' clinical knowledge was equivalent to that of recent residency graduates. The role testing can play in enhancing expertise is described. PMID- 27262156 TI - Academic Peer Detailing-The Preparation and Experience of Detailers Involved in a Project to Disseminate a Comparative Effectiveness Module. AB - INTRODUCTION: Academic detailing uses communication skills, relationship building, and feedback to facilitate behavior change. This report, part of a larger initiative to disseminate evidence summaries of systematic reviews, demonstrates the feasibility of disseminating a comparative effectiveness module to physicians using peer detailers and examines the development of faculty for this process. We describe planning and implementation of a train-the-detailer session, detailer reactions to the process, and results of the dissemination project. METHODS: We recruited 10 experienced primary care clinical faculties in Family and Social Medicine at the Albert Einstein College of Medicine. Detailers attended a 90-minute train-the-detailer session and detailed 150 practitioners at community practices. We evaluated the experiences of the learners and detailers with questionnaires, a focus group, and individual interviews of the detailers. RESULTS: The experiences of detailing in different contexts were uniformly positive. Learners felt the materials were valuable, and that they would implement them or already had implemented them. In the postsurvey completed by 65 of the 150 detailed learners, 97% percent stated that they changed their practice or had already incorporated the practice change before the detailing. All detailers reported a change in their own practice. Detailers found the teaching materials and detailers' guide helpful. Some initially expressed a concern about not knowing enough, which lessened with detailing experience. DISCUSSION: Peer detailing seems doable and well received, especially with the availability of high quality, previously prepared, and tested evidence-based content and materials. Detailers were easily recruited and trained to apply their teaching skills in this new format. The amount of time spent in training sessions on detailing training as opposed to content mastery can be adjusted depending on faculty needs. PMID- 27262157 TI - Building and Participating in a Simulation: Exploring a Continuing Education Intervention Designed to Foster Reflective Practice Among Experienced Clinicians. AB - INTRODUCTION: Engaging health professionals in the processes of first building and then participating in simulations has not yet been explored. This qualitative study explored the experience of building and participating in a simulation as an educational intervention with experienced clinicians. METHODS: Pediatric rehabilitation clinicians, along with a patient facilitator and standardized patients, created simulations and subsequently participated in a live simulation. The educational content of the simulation was culturally sensitive communication. We collected participants' perspectives about the process from individual journal entries and focus groups. A thematic analysis of these data sources was conducted. RESULTS: Participants described a process of building and participating in a simulation that provided: 1) a unique opportunity for clinicians to reflect on their current practice; 2) a venue to identify different perspectives through discussion and action in a group; and 3) a safe environment for learning. DISCUSSION: The combined process of building and participating in a simulation stimulated reflection about the clinicians' own abilities in culturally sensitive communication through discussion, practice, and feedback. It provided a safe environment for participants to share their multiple perspectives and to develop new ways of communicating. This type of educational intervention may contribute to the continuing education of experienced clinicians in both academic and community settings. PMID- 27262158 TI - Influences on the Patient-Physician Relationship: No Quick Fix. PMID- 27262159 TI - The prognostic yield of biomarkers harvested in chemotherapy-naive stage II colon cancer: can we separate the wheat from the chaff? AB - The TNM-system fails to accurately predict disease recurrence in a considerate number of patients. While node-negative (stage II) colon cancer is considered to have an overall good prognosis, the 5-year cancer-specific survival is reported at 81-83% in patients who did not have adjuvant chemotherapy. Thus, reliance on node-status alone has lead to under-treatment in a subgroup of stage II patients with an unfavorable prognosis. The search for new and better prognosticators in stage II colon cancer has suggested several proposed biomarkers of better prognostication and prediction. However, few such biomarkers have reached widespread clinical utility. For the clinician swimming in the sea of emerging biomarkers, it may be hard to recognize the true floating aid from the surrounding debris in the search for more precise decision-making. Proposed markers include microsatellite instability (MSI), KRAS mutations and BRAF mutations, but a number of gene panels and consensus molecular subtypes are proposed for clinical prediction and prognostication as well. While several studies suggest such biomarkers or panels to have a prognostic role in subgroups of patients, a number of studies are reported in heterogeneous groups with in part discordant findings, which again distorts the predictive and prognostic ability of each marker. Lack of homogeneous cohorts, underpowered studies in strict subgroups and challenges in analytical and clinical validity may hamper the progress towards widespread clinical utility. The harvest of prognostic biomarkers in colon cancer has yielded a huge number of candidates for which it is now time to separate the wheat from the chaff. PMID- 27262160 TI - Prognostic Factors, Treatment, and Survival in Dermatofibrosarcoma Protuberans. AB - Importance: There is limited information regarding the influence of patient demographics, tumor characteristics, and treatment type on the survival of patients with dermatofibrosarcoma protuberans (DFSP). Objective: To assess prognostic factors and to evaluate the influence of treatment modality on overall survival of patients with DFSP. Design, Setting, and Participants: We examined DFSP using data for 3686 patients with histologically confirmed cases of DFSP diagnosed between 1972 and 2012 from the 18 US regional registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program, with linkage to demographic data from the US Census Bureau for median household income (MHI). The analysis was performed in February 2016. Main Outcomes and Measures: The primary outcome measures were tumor characteristics, prognostic factors, and overall survival in months. Results: There were 3686 cases of DFSP examined. Older age (hazard ratio [HR], 1.08; 95% CI, 1.06-1.10; P < .001), male sex (HR, 1.97; 95% CI, 1.09-3.55; P = .03), and tumor size (HR, 1.09; 95% CI, 1.01-1.18; P = .04) were significantly associated with poorer overall survival in a controlled analysis. Older age (odds ratio [OR], 1.01; 95% CI, 1.00-1.02; P = .01), male sex (OR, 1.95; 95% CI, 1.57-2.42; P < .001), and black race (OR, 1.78; 95% CI, 1.37-2.32; P < .001) were associated with larger (>=3.0 cm) tumors at presentation. Treatment modality did not influence overall survival; however, differences in patient characteristics affected the treatment received. Older age at presentation (OR, 1.02; 95% CI, 1.01-1.03; P =.01), black race (OR, 1.82; 95% CI, 1.13-2.92; P = .01), large tumor size (OR, 1.15; 95% CI, 1.09-1.21; P < .001), and head or neck location (OR, 4.63; 95% CI, 2.66-8.07; P <.001) increased the likelihood of a patient receiving surgery and radiation over surgery alone. In addition, white patients (OR, 0.51; 95% CI, 0.30-0.87; P=.01), women (OR, 0.53; 95% CI, 0.36-0.78; P <.001), and patients with a higher MHI (OR, 1.27; 95% CI, 1.11-1.46; P <.001) were more likely to receive Mohs micrographic surgery (MMS) over excision. Conclusions and Relevance: Age at diagnosis, male sex, and DFSP tumor size appear to be important prognostic factors. Treatment modality did not significantly influence survival; however, patient and tumor characteristics influence treatment modality. PMID- 27262162 TI - Genetic variability, local selection and demographic history: genomic evidence of evolving towards allopatric speciation in Asian seabass. AB - Genomewide analysis of genetic divergence is critically important in understanding the genetic processes of allopatric speciation. We sequenced RAD tags of 131 Asian seabass individuals of six populations from South-East Asia and Australia/Papua New Guinea. Using 32 433 SNPs, we examined the genetic diversity and patterns of population differentiation across all the populations. We found significant evidence of genetic heterogeneity between South-East Asian and Australian/Papua New Guinean populations. The Australian/Papua New Guinean populations showed a rather lower level of genetic diversity. FST and principal components analysis revealed striking divergence between South-East Asian and Australian/Papua New Guinean populations. Interestingly, no evidence of contemporary gene flow was observed. The demographic history was further tested based on the folded joint site frequency spectrum. The scenario of ancient migration with historical population size changes was suggested to be the best fit model to explain the genetic divergence of Asian seabass between South-East Asia and Australia/Papua New Guinea. This scenario also revealed that Australian/Papua New Guinean populations were founded by ancestors from South East Asia during mid-Pleistocene and were completely isolated from the ancestral population after the last glacial retreat. We also detected footprints of local selection, which might be related to differential ecological adaptation. The ancient gene flow was examined and deemed likely insufficient to counteract the genetic differentiation caused by genetic drift. The observed genomic pattern of divergence conflicted with the 'genomic islands' scenario. Altogether, Asian seabass have likely been evolving towards allopatric speciation since the split from the ancestral population during mid-Pleistocene. PMID- 27262163 TI - The context dependence of assortative mating: a demonstration with conspecific salmonid populations. AB - Assortative mating is thought to play a key role in reproductive isolation. However, most experimental studies of assortative mating do not take place in multiple natural environments, and hence, they ignore its potential context dependence. We implemented an experiment in which two populations of brown trout (Salmo trutta) with different natural flow regimes were placed into semi-natural stream channels under two different artificial flow regimes. Natural reproduction was allowed, and reproductive isolation was measured by means of parentage assignment to compare within-population vs. between-population male-female mating and relative offspring production. For both metrics, reproductive isolation was highly context dependent: no isolation was evident under one flow regime, but strong isolation was evident under the other flow regime. These patterns were fully driven by variance in the mating success of males from one of the two populations. Our results highlight how reproductive isolation through assortative mating can be strongly context dependent, which could have dramatic consequences for patterns of gene flow and speciation under environmental change. PMID- 27262161 TI - Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord. AB - This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas. PMID- 27262164 TI - Chronic hepatitis B in children: Therapeutic challenges and perspectives. AB - Chronic hepatitis B virus (HBV) infection and HBV-related hepatitis in children remains an unmet medical need, as current treatments are only partially effective, and only in a limited number of affected children. So-called "immunotolerant" children have not shown increased serological responses to available treatments. In cases involving more active disease, serological response has only been obtained in approximately one-third of patients when using interferon, while other cases exhibited virological response solely under continuous treatment with nucleoside analogs. Guidelines have recently been established to aid pediatricians in effectively managing this condition. With the available medications, no treatment is so far indicated for immunotolerant children, but only for cases presenting increased alanine aminotransferase levels to over 1.5-2 times the upper limit of normal for over 6 months, and without spontaneous HB envelope antigen to antibody seroconversion. The therapeutic arsenal approved by the Food and Drugs Administration and European Medicines Agency for children remains limited because of the lack of large-scale clinical trials validating treatments already approved for the adult population. Yet, the recent discovery of a specific HBV-cell surface receptor, NTCP, allows for new treatment perspectives regarding the future. PMID- 27262165 TI - Insight from Frogs: Sonic Hedgehog Gene Expression and a Re-evaluation of the Vertebrate Odontogenic Band. AB - While the identification of conserved processes across multiple taxa leads to an understanding of fundamental developmental mechanisms, the ways in which different animals fail to conform to common developmental processes can elucidate how evolution modifies development to result in the vast array of morphologies seen today-the developmental mechanisms that lead to anatomical variation. Odontogenesis-how teeth are initiated and formed-is well suited to the examination of both developmental conservation and phenotypic diversity. We suggest here that the study of early tooth development, the period of odontogenic band development, reveals departures from conserved mechanisms that question the role of players in the developmental process. In the earliest stages of odontogenesis, Sonic hedgehog (Shh) gene expression is interpreted as critical evidence of tooth initiation prior to any histological indication. However, a detailed examination of studies of tooth development across a wide range of taxa reveals that several vertebrate species fail to conform to the expectations of the Shh Consensus Model, calling for a reconsideration of the assumed causality of epithelial Shh in tooth initiation. We present new Shh gene expression data for an amphibian, the frog Silurana (Xenopus) tropicalis. In these animals, craniofacial and odontogenic developmental processes are more disjunct, and thereby provide a natural test of the hypothesis that Shh is immediately required for subsequent tooth development. Our results suggest that Shh expression may actually be related to the formation of the mouth rather than a required precursor to subsequent tooth formation. Anat Rec, 299:1099-1109, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27262166 TI - Sonoembryology of the fetal posterior fossa at 11 + 3 to 13 + 6 gestational weeks on three-dimensional transvaginal ultrasound. AB - OBJECTIVE: To describe the sonographic appearance and temporal changes of the structures of the posterior cranial fossa in fetuses at a crown-rump length (CRL) between 45 and 84 mm in transvaginal acquired three-dimensional volume blocks. METHODS: This was a prospective, cross-sectional, observational study including 80 fetuses, whose mothers attended Kepler University Hospital Linz or the Ambulatorium fur Fetalmedizin Feldkirch for first-trimester sonography. Three dimensional volume blocks were acquired in a standardized way and after processing the sonographic characteristics of the brainstem, cerebellar vermis, choroid plexus, anterior membranous area (AMA) and Blake's metapore were described. Measurements of the length of the cerebellar vermis, the length of the AMA and the medulla-oblongata-pons angle (MOPA) were performed. In 20 fetuses the intra- and interobserver repeatability was calculated. RESULTS: The sonomorphologic characteristics of posterior fossa structures as cerebellar vermis, AMA, Blake's metapore, choroid plexus, pons and medulla oblongata were described. There is a significant correlation between CRL and vermis length, CRL and MOPA and CRL and AMA. CONCLUSIONS: Transvaginal three-dimensional sonography allows a detailed depiction of the structures of the posterior fossa and their temporal course in early pregnancy. (c) 2016 John Wiley & Sons, Ltd. PMID- 27262167 TI - Current view on regulation of voltage-gated sodium channels by calcium and auxiliary proteins. AB - In cardiac and skeletal myocytes, and in most neurons, the opening of voltage gated Na(+) channels (NaV channels) triggers action potentials, a process that is regulated via the interactions of the channels' intercellular C-termini with auxiliary proteins and/or Ca(2+) . The molecular and structural details for how Ca(2+) and/or auxiliary proteins modulate NaV channel function, however, have eluded a concise mechanistic explanation and details have been shrouded for the last decade behind controversy about whether Ca(2+) acts directly upon the NaV channel or through interacting proteins, such as the Ca(2+) binding protein calmodulin (CaM). Here, we review recent advances in defining the structure of NaV intracellular C-termini and associated proteins such as CaM or fibroblast growth factor homologous factors (FHFs) to reveal new insights into how Ca(2+) affects NaV function, and how altered Ca(2+) -dependent or FHF-mediated regulation of NaV channels is perturbed in various disease states through mutations that disrupt CaM or FHF interaction. PMID- 27262169 TI - Endovascular treatment of posterior condylar canal dural arteriovenous fistula. AB - Posterior condylar canal dural arteriovenous fistulas (PCC DAVFs) are rare lesions that may present with pulse-synchronous bruit. In cases with venous reflux there is a risk of haemorrhage or even dementia. Diagnosis and endovascular treatment require a profound knowledge of the vascular anatomy of the craniocervical junction and comprehensive neurovascular imaging. We describe the clinical presentation, angiographic imaging and endovascular treatment of a PCC DAVF in a female patient with pulse-synchronous bruit as the presenting symptom. The fistula drained almost exclusively into the sigmoid sinus and internal jugular vein. There was no intracranial reflux. The PCC DAVF was treated with transvenous coil occlusion of the fistulous pouch in the condylar canal. Symptoms resolved immediately after intervention and the patient recovered quickly without any neurological deficits. MR angiography confirmed occlusion of the DAVF. The dural sinus was patent with normal blood flow. PMID- 27262170 TI - Effects on Deaf Patients of Medication Education by Pharmacists. AB - Deaf people often experience difficulty in understanding medication information provided by pharmacists due to communication barriers. We held medication education lectures for deaf and hard of hearing (HH) individuals and examined the extent to which deaf participants understood medication-related information as well as their attitude about medication. We used two questionnaires to compare the results from the deaf participants with those from the HH and hearing participants. We found that before the lecture, the deaf participants' understanding of medication use was lower than that of the HH and hearing participants. The deaf participants' knowledge increased after the lecture, but did not improve to the level exhibited by the HH participants. However, the deaf participants felt confident using medication despite their low comprehension levels. In conclusion, adjusting the medication information provided by pharmacists according to the recipient's reading level could help improve deaf patients' knowledge; however, such measures might not increase deaf patients' comprehension levels sufficiently. PMID- 27262168 TI - Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate Cancer. AB - Importance: A critical decision in the management of metastatic castration resistant prostate cancer (mCRPC) is when to administer an androgen receptor signaling (ARS) inhibitor or a taxane. Objective: To determine if pretherapy nuclear androgen-receptor splice variant 7 (AR-V7) protein expression and localization on circulating tumor cells (CTCs) is a treatment-specific marker for response and outcomes between ARS inhibitors and taxanes. Design, Setting, and Participants: For this cross-sectional cohort study at Memorial Sloan Kettering Cancer Center, 265 men with progressive mCRPC undergoing a change in treatment were considered; 86 were excluded because they were not initiating ARS or taxane therapy; and 18 were excluded for processing time constraints, leaving 161 patients for analysis. Between December 2012 and March 2015, blood was collected and processed from patients with progressive mCRPC immediately prior to new line of systemic therapy. Patients were followed up to 3 years. Main Outcomes and Measures: Prostate-specific antigen (PSA) response, time receiving therapy, radiographic progression-free survival (rPFS), and overall survival (OS). Results: Overall, of 193 prospectively collected blood samples from 161 men with mCRPC, 191 were evaluable (128 pre-ARS inhibitor and 63 pretaxane). AR-V7 positive CTCs were found in 34 samples (18%), including 3% of first-line, 18% of second-line, and 31% of third- or greater line samples. Patients whose samples had AR-V7-positive CTCs before ARS inhibition had resistant posttherapy PSA changes (PTPC), shorter rPFS, shorter time on therapy, and shorter OS than those without AR-V7-positive CTCs. Overall, resistant PTPC were seen in 65 of 112 samples (58%) without detectable AR-V7-positive CTCs prior to ARS inhibition. There were statistically significant differences in OS but not in PTPC, time on therapy, or rPFS for patients with or without pretherapy AR-V7-positive CTCs treated with a taxane. A multivariable model adjusting for baseline factors associated with survival showed superior OS with taxanes relative to ARS inhibitors when AR-V7-positive CTCs were detected pretherapy (hazard ratio, 0.24; 95% CI, 0.10-0.57; P = .035). Conclusions and Relevance: The results validate CTC nuclear expression of AR-V7 protein in men with mCRPC as a treatment-specific biomarker that is associated with superior survival on taxane therapy over ARS directed therapy in a clinical practice setting. Continued examination of this biomarker in prospective studies will further aid clinical utility. PMID- 27262171 TI - EF Hand Protein IBA2 Promotes Cell Proliferation in Breast Cancers via Transcriptional Control of Cyclin D1. AB - EF hand (EFh) domain-containing proteins have been implicated in malignant progression, but their precise functional contributions are uncertain. Here, we report evidence that the EFh protein IBA2 promotes the proliferation of breast cancer cells by facilitating their transit through the G1-S cell-cycle transition. Mechanistic investigations revealed that IBA2 acted at the transcriptional level to promote the expression of the critical cell-cycle regulator cyclin D1. Clinically, we found that levels of IBA2 were significantly upregulated in breast cancer specimens, where its expression correlated positively with histologic grade. Our results suggest a key role for IBA2 in mammary tumorigenesis. Cancer Res; 76(15); 4535-45. (c)2016 AACR. PMID- 27262173 TI - AIMP2 Controls Intestinal Stem Cell Compartments and Tumorigenesis by Modulating Wnt/beta-Catenin Signaling. AB - Wnt/beta-catenin (CTNNB1) signaling is crucial for the proliferation and maintenance of intestinal stem cells (ISC), but excessive activation leads to ISC expansion and eventually colorectal cancer. Thus, negative regulators are required to maintain optimal levels of Wnt/beta-catenin signaling. Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMP) function in protein synthesis, but have also been implicated in signaling cascades affecting angiogenesis, immunity, and apoptosis. In this study, we investigated the relationship between AIMP2 and Wnt/beta-catenin signaling in a murine model of intestinal homeostasis and tumorigenesis. Hemizygous deletion of Aimp2 resulted in enhanced Wnt/beta-catenin signaling, increased proliferation of cryptic epithelial cells, and expansion of ISC compartments. In an Apc(Min/+) background, Aimp2 hemizygosity increased adenoma formation. Mechanistically, AIMP2 disrupted the interaction between AXIN and Dishevelled-1 (DVL1) to inhibit Wnt/beta-catenin signaling by competing with AXIN. Furthermore, AIMP2 inhibited intestinal organoid formation and growth by suppressing Wnt/beta-catenin signaling in an Aimp2 gene dosage-dependent manner. Collectively, our results showed that AIMP2 acts as a haploinsufficient tumor suppressor that fine-tunes Wnt/beta-catenin signaling in the intestine, illuminating the regulation of ISC abundance and activity. Cancer Res; 76(15); 4559-68. (c)2016 AACR. PMID- 27262174 TI - Three-dimensional planning and printing of guides and templates for reconstruction of the mandibular ramus and condyle using autogenous costochondral grafts. PMID- 27262172 TI - A Novel Chemotherapeutic Agent to Treat Tumors with DNA Mismatch Repair Deficiencies. AB - Impairing the division of cancer cells with genotoxic small molecules has been a primary goal to develop chemotherapeutic agents. However, DNA mismatch repair (MMR)-deficient cancer cells are resistant to most conventional chemotherapeutic agents. Here we have identified baicalein as a small molecule that selectively kills MutSalpha-deficient cancer cells. Baicalein binds preferentially to mismatched DNA and induces a DNA damage response in a MMR-dependent manner. In MutSalpha-proficient cells, baicalein binds to MutSalpha to dissociate CHK2 from MutSalpha leading to S-phase arrest and cell survival. In contrast, continued replication in the presence of baicalein in MutSalpha-deficient cells results in a high number of DNA double-strand breaks and ultimately leads to apoptosis. Consistently, baicalein specifically shrinks MutSalpha-deficient xenograft tumors and inhibits the growth of AOM-DSS-induced colon tumors in colon-specific MSH2 knockout mice. Collectively, baicalein offers the potential of an improved treatment option for patients with tumors with a DNA MMR deficiency. Cancer Res; 76(14); 4183-91. (c)2016 AACR. PMID- 27262175 TI - Balaclava bandage: a new method to support dressings after surgery on head and neck. PMID- 27262176 TI - Gender differences in management and clinical outcomes of atrial fibrillation patients. AB - BACKGROUND: Prior research has identified gender differences in the epidemiology and clinical management of atrial fibrillation (AF). The primary aim of this study is to systematically analyze a cohort of AF men and women and evaluate their baseline demographics, treatment, and clinical outcomes by gender. METHODS: We examined the records of 5976 (42% women) consecutive AF patients who were prescribed at least one anti-arrhythmic drug between 2006 and 2013. From this cohort, 4311 (72%) patients had anticoagulation data available and were included in the final analysis. Time to clinical events was assessed using survival analysis and adjusted for covariates using Cox regression. RESULTS: Compared to men, women were older (73 years vs. 67 years, p<0.001), had higher CHADS2 scores (1.9 vs. 1.5, p<0.001), and fewer cardiac comorbidities. Compared to men, women were more often prescribed sotalol and less often dofetilide (p<0.001). Women were also less likely to be anticoagulated (76.8% vs. 82.5%, p<0.001). Over a mean follow-up of 40 months, women were more likely to die (HR 1.21, p=0.037) or to have an ischemic stroke (HR 1.35, p=0.058). Women also had higher rates of atrioventricular-nodal ablation (adjusted HR 2.11, p<0.001) and pacemaker implantation (adjusted HR 1.69, p<0.001) procedures, but lower rates of electrical cardioversions, AF ablations, and maze surgeries. CONCLUSIONS: There are significant gender differences in baseline demographics and clinical outcomes of AF patients. Women have higher mortality and ischemic strokes and are less often prescribed anticoagulation therapy despite higher CHADS2 scores. These data have important clinical implications. PMID- 27262178 TI - Solid anaerobic digestion batch of bio-waste as pre-treatment for improving amendment quality: The effect of inoculum recirculation. AB - The effect of solid anaerobic digestion batch (SADB) on bio-waste performed with and without inoculum on the quality of the final amendment was investigated by means of determining the content of organic carbon, humic and fulvic acids and the degree of humification. Two different processes were compared: composting and SADB with post-composting. Six parallel tests were performed. In three of these tests the SADB was inoculated mixing the bio-waste with the digestate from the previous run in a 1:1 ratio by weight. The amendment obtained by the SADB with post-composting treatment, in which the SADB was not inoculated, had an organic carbon content ranging from 15.5% TS to 30.3% TS resulting from 1% up to 14% higher than that of the corresponding composting processes. Similar results were achieved for the degree of humification. On the other hand SADB in which the inoculum was used generated about 300NL/kgVS of biogas instead of about 267NL/kgVS for non-inoculated runs. PMID- 27262179 TI - Guidelines for professional practice in reporting information about measurement instruments in health research. PMID- 27262177 TI - The Neural Consequences of Age-Related Hearing Loss. AB - During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension. PMID- 27262180 TI - Male and female physical intimate partner violence and socio-economic position: a cross-sectional international multicentre study in Europe. AB - OBJECTIVES: This work explores the association between socio-economic position (SEP) and intimate partner violence (IPV) considering the perspectives of men and women as victims, perpetrators and as both (bidirectional). STUDY DESIGN: Cross sectional international multicentre study. METHODS: A sample of 3496 men and women, (aged 18-64 years), randomly selected from the general population of residents from six European cities was assessed: Athens; Budapest; London; Ostersund; Porto; and Stuttgart. Their education (primary, secondary and university), occupation (upper white collar, lower white collar and blue collar) and unemployment duration (never, <=12 months and >12 months) were considered as SEP indicators and physical IPV was measured with the Revised Conflict Tactics Scales. RESULTS: Past year physical IPV was declared by 17.7% of women (3.5% victims, 4.2% perpetrators and 10.0% bidirectional) and 19.8% of men (4.1% victims, 3.8% perpetrators and 11.9% bidirectional). Low educational level (primary vs university) was associated with female victimisation (adjusted odds ratio, 95% confidence interval: 3.2; 1.3-8.0) and with female bidirectional IPV (4.1, 2.4-7.1). Blue collar occupation (vs upper white) was associated with female victimisation (2.1, 1.1-4.0), female perpetration (3.0, 1.3-6.8) and female bidirectional IPV (4.0, 2.3-7.0). Unemployment duration was associated with male perpetration (>12 months of unemployment vs never unemployed: 3.8; 1.7 8.7) and with bidirectional IPV in both sex (women: 1.8, 1.2-2.7; men: 1.7, 1.0 2.8). CONCLUSIONS: In these European centres, physical IPV was associated with a disadvantaged SEP. A consistent socio-economic gradient was observed in female bidirectional involvement, but victims or perpetrators-only presented gender specificities according to levels of education, occupation differentiation and unemployment duration potentially useful for designing interventions. PMID- 27262181 TI - Development of a protocol to quantify local bone adaptation over space and time: Quantification of reproducibility. AB - In vivo micro-computed tomography (uCT) scanning of small rodents is a powerful method for longitudinal monitoring of bone adaptation. However, the life-time bone growth in small rodents makes it a challenge to quantify local bone adaptation. Therefore, the aim of this study was to develop a protocol, which can take into account large bone growth, to quantify local bone adaptations over space and time. The entire right tibiae of eight 14-week-old C57BL/6J female mice were consecutively scanned four times in an in vivo uCT scanner using a nominal isotropic image voxel size of 10.4um. The repeated scan image datasets were aligned to the corresponding baseline (first) scan image dataset using rigid registration. 80% of tibia length (starting from the endpoint of the proximal growth plate) was selected as the volume of interest and partitioned into 40 regions along the tibial long axis (10 divisions) and in the cross-section (4 sectors). The bone mineral content (BMC) was used to quantify bone adaptation and was calculated in each region. All local BMCs have precision errors (PE%CV) of less than 3.5% (24 out of 40 regions have PE%CV of less than 2%), least significant changes (LSCs) of less than 3.8%, and 38 out of 40 regions have intraclass correlation coefficients (ICCs) of over 0.8. The proposed protocol allows to quantify local bone adaptations over an entire tibia in longitudinal studies, with a high reproducibility, an essential requirement to reduce the number of animals to achieve the necessary statistical power. PMID- 27262182 TI - Multi-segment analysis of spinal kinematics during sit-to-stand in patients with chronic low back pain. AB - While alterations in spinal kinematics have been frequently reported in patients with chronic low back pain (CLBP), a better characterization of the kinematics during functional activities is needed to improve our understanding and therapeutic solutions for this condition. Recent studies on healthy subjects showed the value of analyzing the spine during sit-to-stand transition (STST) using multi-segment models, suggesting that additional knowledge could be gained by conducting similar assessments in CLBP patients. The objectives of this study were to characterize three dimensional kinematics at the lower lumbar (LLS), upper lumbar (ULS), lower thoracic (LTS) and upper thoracic (UTS) joints during STST, and to test the hypothesis that CLBP patients perform this movement with smaller angle and angular velocity compared to asymptomatic controls. Ten CLBP patients (with minimal to moderate disability) and 11 asymptomatic controls with comparable demographics (52% male, 37.4+/-5.6 years old, 22.5+/-2.8kg/m(2)) were tested using a three-dimensional camera-based system following previously proposed protocols. Characteristic patterns of movement were identified at the LLS, ULS and UTS joints in the sagittal plane only. Significant differences in the form of smaller sagittal-plane angle and smaller angular velocity in the patient group compared to the control group were observed at these three joints. This indicated a more rigid spine in the patient group and suggested that CLBP rehabilitation could potentially be enhanced by targeting movement deficits in functional activities. The results further recommended the analysis of STST kinematics using a pelvis-lumbar-thoracic model including lower and upper lumbar and thoracic segments. PMID- 27262183 TI - [ISO 45001: Opportunity for healthcare organizations in improving occupational health]. PMID- 27262184 TI - A Detailed Analysis of Mandibular Angle Fractures: Epidemiology, Patterns, Treatments, and Outcomes. AB - PURPOSE: The purpose was to analyze mandibular angle fractures by examining epidemiologic trends and mechanisms of injury and to determine whether a statistically meaningful relation existed between certain treatment modalities and patient outcomes. MATERIALS AND METHODS: A retrospective chart analysis was performed, and data were limited to 1 operator. Treatment variables were methods of fixation, postoperative intermaxillary fixation (IMF), and retention versus extraction of teeth in the line of fracture. Outcomes were rates of postoperative infection, fracture healing, and overall patient comfort. Analysis was performed using the Fisher exact test, Wald test, and chi(2) test, with a P value less than .05 considered significant. RESULTS: One hundred three patients were included in this study. The mean age was 30.4 years, most patients were men, and most injuries occurred during physical altercations and on the left side of the face. The most common concomitant fracture was of the contralateral parasymphysis. A statistically meaningful relation was noted between methods of fixation and healing and overall patient comfort, with the Champy technique and reconstruction plate being associated with the highest rates of bony union and patient comfort. No statistically relevant correlation was found between methods of fixation and rates of infection. There was no statistically relevant link for extraction versus retention of healthy teeth in the line of fracture or use of IMF with patient comfort, postoperative infection, or fracture healing. CONCLUSION: Although the Champy technique and reconstruction plates were associated with better postoperative outcomes, such as patient comfort and fracture healing, these should not be used interchangeably. IMF and extraction versus retention of teeth in the line of fracture did not influence any of the outcomes. PMID- 27262185 TI - Doing the counter-regulation shuffle: The importance of flexibility and hunger for predicting food consumption following a preload. AB - OBJECTIVES: This study utilised the preload paradigm to evaluate whether trait like dieting attitudes and behaviours (dietary restraint and flexibility in dieting rules) and context-specific factors (negative mood and hunger) predict food consumption among male and female participants. METHODS: Following a high calorie preload, 79 participants aged 18-40 completed a deceptive taste test in which they were encouraged to eat as much of the taste test foods as desired, and this ad libitum intake was measured. RESULTS: Although each predictor (except negative mood) predicted consumption when tested individually, regression analyses revealed that dieting flexibility and current hunger were the strongest unique predictors of intake. Mood failed to directly predict food consumption, nor did it moderate the relationship between restraint and food intake. CONCLUSION: Collectively, findings suggest that emphasis on dietary restraint in preload studies may be misplaced, as other proximal and stable factors may better predict food consumption. PMID- 27262186 TI - Pacemaker extrusion. PMID- 27262188 TI - Overview of Fusion Tags for Recombinant Proteins. AB - Virtually all recombinant proteins are now prepared using fusion domains also known as "tags". The use of tags helps to solve some serious problems: to simplify procedures of protein isolation, to increase expression and solubility of the desired protein, to simplify protein refolding and increase its efficiency, and to prevent proteolysis. In this review, advantages and disadvantages of such fusion tags are analyzed and data on both well-known and new tags are generalized. The authors own data are also presented. PMID- 27262189 TI - Chlorophylls d and f and Their Role in Primary Photosynthetic Processes of Cyanobacteria. AB - The finding of unique Chl d- and Chl f-containing cyanobacteria in the last decade was a discovery in the area of biology of oxygenic photosynthetic organisms. Chl b, Chl c, and Chl f are considered to be accessory pigments found in antennae systems of photosynthetic organisms. They absorb energy and transfer it to the photosynthetic reaction center (RC), but do not participate in electron transport by the photosynthetic electron transport chain. However, Chl d as well as Chl a can operate not only in the light-harvesting complex, but also in the photosynthetic RC. The long-wavelength (Qy) Chl d and Chl f absorption band is shifted to longer wavelength (to 750 nm) compared to Chl a, which suggests the possibility for oxygenic photosynthesis in this spectral range. Such expansion of the photosynthetically active light range is important for the survival of cyanobacteria when the intensity of light not exceeding 700 nm is attenuated due to absorption by Chl a and other pigments. At the same time, energy storage efficiency in photosystem 2 for cyanobacteria containing Chl d and Chl f is not lower than that of cyanobacteria containing Chl a. Despite great interest in these unique chlorophylls, many questions related to functioning of such pigments in primary photosynthetic processes are still not elucidated. This review describes the latest advances in the field of Chl d and Chl f research and their role in primary photosynthetic processes of cyanobacteria. PMID- 27262187 TI - Membrane prestin expression correlates with the magnitude of prestin-associated charge movement. AB - Full expression of electromotility, generation of non-linear capacitance (NLC), and high-acuity mammalian hearing require prestin function in the lateral wall of cochlear outer hair cells (OHCs). Estimates of the number of prestin molecules in the OHC membrane vary, and a consensus has not emerged about the correlation between prestin expression and prestin-associated charge movement in the OHC. Using an inducible prestin-expressing cell line, we demonstrate that the charge density, but not the voltage at peak capacitance, directly correlates with the amount of prestin in the plasma membrane. This correlation is evident in studies involving a controlled increase of prestin expression with time after induction and inducer dose-response. Conversely, membrane prestin levels and charge density gradually decline together following the reduction of prestin levels from a steady state by removal of the inducer. Thus, charge density directly correlates with the level of membrane prestin expression, whereas changing membrane levels of prestin have no effect on the voltage at peak capacitance in this inducible prestin-expressing cell line. PMID- 27262190 TI - Structure and Functions of Linker Histones. AB - Linker histones such as variants H1, H5, and other similar proteins play an important role in regulation of chromatin structure and dynamics. However, interactions of linker histones with DNA and proteins, as well as specific functions of their different variants, are poorly studied. This is because they acquire tertiary structure only when interacting with a nucleosome, and because of limitations of currently available methods. However, deeper investigation of linker histones and their interactions with other proteins will address a number of important questions - from structure of compacted chromatin to regulation of early embryogenesis. In this review, structures of histone H1 variants and its interaction with chromatin DNA are considered. A possible functional significance of different H1 variants, a role of these proteins in maintaining interphase chromatin structure, and interactions of linker histones with other cellular proteins are also discussed. PMID- 27262191 TI - Age-Related Changes in Antioxidant and Glutathione S-Transferase Enzyme Activities in the Asian Clam. AB - Aging is accompanied by increased production of free oxygen radicals and impairment of normal cellular functions. The aim of this work was to provide preliminary data on age-related differences in the activities of antioxidant enzymes and phase II biotransformation enzyme glutathione S-transferase (GST) in a wild population of the Asian clam Corbicula fluminea. The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and GST were assessed in visceral mass of four age classes (0+-, 1+-, 2+-, and 3+-year-old) of C. fluminea clams. Age-related changes were seen in antioxidant enzyme status: levels of total SOD (totSOD) (P < 0.05), MnSOD, and CuZnSOD (P < 0.05) activities increased progressively during aging from younger to older clams. Changes in CAT and GR activities with advancing age were found, the levels being the highest in age class II, then being lower in age classes III and IV (P < 0.05). Activities of GPX and GST were lower in the senescent individuals (2+- and 3+-year-old clams) compared with young individuals (0+- and 1+-year-old clams). Overall, the decline of glutathione-dependent enzyme activities, coupled with higher and lower activities of totSOD and CAT, respectively, as the individual grows older, may render the older animals more susceptible to oxidative stress. Data reported here are not intended to be exhaustive since they concern only age/size structure of the population at one locality, so more detailed studies on both the developmental stages and levels of antioxidant enzymes of this new alien species in Serbian rivers are required. PMID- 27262192 TI - Interaction of Nucleotide Excision Repair Protein XPC-RAD23B with DNA Containing Benzo[a]pyrene-Derived Adduct and Apurinic/Apyrimidinic Site within a Cluster. AB - The combined action of reactive metabolites of benzo[a]pyrene (B[a]P) and oxidative stress can lead to cluster-type DNA damage that includes both a bulky lesion and an apurinic/apyrimidinic (AP) site, which are repaired by the nucleotide and base excision repair mechanisms - NER and BER, respectively. Interaction of NER protein XPC-RAD23B providing primary damage recognition with DNA duplexes containing a B[a]P-derived residue linked to the exocyclic amino group of a guanine (BPDE-N(2)-dG) in the central position of one strand and AP site in different positions of the other strand was analyzed. It was found that XPC-RAD23B crosslinks to DNA containing (+)-trans-BPDE-N(2)-dG more effectively than to DNA containing cis-isomer, independently of the AP site position in the opposite strand; protein affinity to DNA containing one of the BPDE-N(2)-dG isomers depends on the AP site position in the opposite strand. The influence of XPC-RAD23B on hydrolysis of an AP site clustered with BPDE-N(2)-dG catalyzed by the apurinic/apyrimidinic endonuclease 1 (APE1) was examined. XPC-RAD23B was shown to stimulate the endonuclease and inhibit the 3'-5' exonuclease activity of APE1. These data demonstrate the possibility of cooperation of two proteins belonging to different DNA repair systems in the repair of cluster-type DNA damage. PMID- 27262193 TI - Effect of Thrombin Inhibitors on Positive Feedback in the Coagulation Cascade. AB - The coagulation cascade is a series of sequential reactions of limited proteolysis of protein factors resulting in generation of thrombin. Thrombin mediates both positive and negative feedback in regulating this cascade by taking part in activation of several factors. Some thrombin inhibitors, by affecting positive feedback, inhibit generation of thrombin itself. In the current study, we used two thrombin inhibitors: argatroban, a low molecular weight reversible competitive inhibitor that binds to the active site, and bivalirudin, a bivalent oligopeptide that blocks the active site and binding center of protein substrates (exosite I). Appearance rate and total amount of thrombin were measured in a thrombin generation assay (TGA) using a fluorescent substrate. We found that argatroban slows the appearance of thrombin and lowers its amount. Bivalirudin also slows appearance of thrombin, but it does not decrease its amount, perhaps because the region being bound to the active site undergoes hydrolysis so that the inhibitor stops binding to thrombin. Many reactions of the coagulation cascade proceed on the surface of phospholipid micelles (PLMs). In the case of argatroban, PLMs do not affect the results of the TGA, whereas for bivalirudin they lower its inhibitory activity. It seems that PLMs stabilize protein complexes (wherein thrombin exosite I is hindered) mediating positive feedback in the coagulation cascade, e.g. complexes of thrombin with factor V and VIII. PMID- 27262194 TI - Identification of a Region of the Polypeptide Chain of Na,K-ATPase alpha-Subunit Interacting with 67-kDa Melittin-Like Protein. AB - It was shown earlier that a 67-kDa protein purified from mouse kidney using polyclonal antibodies against melittin (a peptide from bee venom) interacted with Na,K-ATPase from rabbit kidney. In this study, a 43-kDa proteolytic fragment of Na,K-ATPase alpha-subunit interacting with the 67-kDa melittin-like protein was found. The alpha-subunit was hydrolyzed by trypsin in the presence of 0.5 mM ouabain (E2-conformation of Na,K-ATPase). A proteolytic fragment interacting with the 67-kDa melittin-like protein that was identified by mass-spectrometry is a region of the cytoplasmic domain of Na,K-ATPase alpha-subunit located between amino acid residues 591 and 775. The fragment includes a conservative DPPRA motif that occurs in many P-type ATPases. It was shown earlier that this motif of H,K ATPase from gastric mucosa binds to melittin. We suggest that namely this motif of P-type ATPases is able to interact with proteins containing melittin-like modules. PMID- 27262195 TI - Tankyrase Activity in Organs and Tissues of Mice. AB - Tankyrase, one of the NAD+ ADP-ribosyltransferases, is a target for drugs developed for their anticancer and other pharmacological activities. We designed an assay for estimation of the inhibition or activation of the enzyme in preclinical studies. In mice, the highest specific activity of tankyrase was observed in thymus, spleen, pancreas, and bone marrow. In murine liver, tankyrase is active in ontogenesis and during reparative regeneration; however, the basal activity is hardly detectable in normal liver and most of other organs of adult animals. We suggest that tankyrase is a part of the tissue growth and repair machinery, while its age-dependent inhibition, when an organism stops growing, turns on phenoptosis. PMID- 27262196 TI - DNA with Damage in Both Strands as Affinity Probes and Nucleotide Excision Repair Substrates. AB - Nucleotide excision repair (NER) is a multistep process of recognition and elimination of a wide spectrum of damages that cause significant distortions in DNA structure, such as UV-induced damage and bulky chemical adducts. A series of model DNAs containing new bulky fluoro-azidobenzoyl photoactive lesion dC(FAB) and well-recognized nonnucleoside lesions nFlu and nAnt have been designed and their interaction with repair proteins investigated. We demonstrate that modified DNA duplexes dC(FAB)/dG (probe I), dC(FAB)/nFlu+4 (probe II), and dC(FAB)/nFlu-3 (probe III) have increased (as compared to unmodified DNA, umDNA) structure dependent affinity for XPC-HR23B (Kdum > KdI > KdII ~ KdIII) and differentially crosslink to XPC and proteins of NER-competent extracts. The presence of dC(FAB) results in (i) decreased melting temperature (DeltaTm = -3 degrees C) and (ii) 12 degrees DNA bending. The extended dC(FAB)/dG-DNA (137 bp) was demonstrated to be an effective NER substrate. Lack of correlation between the affinity to XPC-HR23B and substrate properties of the model DNA suggests a high impact of the verification stage on the overall NER process. In addition, DNAs containing closely positioned, well-recognized lesions in the complementary strands represent hardly repairable (dC(FAB)/nFlu+4, dC(FAB)/nFlu-3) or irreparable (nFlu/nFlu+4, nFlu/nFlu-3, nAnt/nFlu+4, nAnt/nFlu-3) structures. Our data provide evidence that the NER system of higher eukaryotes recognizes and eliminates damaged DNA fragments on a multi-criterion basis. PMID- 27262198 TI - Mathematical Model of Self-Oscillations of Activity of Kai Proteins. AB - A non-autocatalytic mathematical model of self-oscillations in vitro in solutions of cyanobacterial Kai proteins (KaiA, KaiB, KaiC) and ATP is suggested. This model describes the process of phosphorylation/dephosphorylation of KaiC protein, which is accelerated by KaiA and inhibited by KaiB. The method of metabolic control analysis is used to show that frequency (period) as well as amplitude of self-oscillations of components of Kai proteins are temperature-compensated. PMID- 27262197 TI - Dynamics of Antagonistic Potency of Rhodobacter capsulatus PG Lipopolysaccharide against Endotoxin-Induced Effects. AB - The dynamics of antagonistic potency of lipopolysaccharide (LPS) isolated from Rhodobacter capsulatus PG on the synthesis of proinflammatory (TNF-alpha, IL 1beta, IL-8, IL-6, IFN-gamma) and antiinflammatory (IL-10, IL-1Ra) cytokines induced by highly stimulatory endotoxins from Escherichia coli or Salmonella enterica have been studied. Using human whole blood, we have shown that R. capsulatus PG LPS inhibited most pronouncedly the endotoxin-induced synthesis of TNF-alpha, IL-1beta, IL-8, and IL-6 during the first 6 h after endotoxin challenge. Similarly, the endotoxin-induced release of IFN-gamma was abolished by R. capsulatus PG LPS as well (24 h). In contrast to the above-mentioned cytokines, the relatively weak antagonistic activity of R. capsulatus PG LPS against endotoxin-triggered production of IL-6 and IL-8 was revealed. Since R. capsulatus PG LPS displays more potent antagonistic activity against deleterious effects of S. enterica LPS than those of E. coli LPS in the cases of such cytokines as IL-1beta (6 and 24 h), IL-6 and IL-8 (4 h), we conclude that the effectiveness of protective action of antagonist is mostly determined by the primary lipid A structure of the employed agonist. PMID- 27262199 TI - Isoferulic Acid Action against Glycation-Induced Changes in Structural and Functional Attributes of Human High-Density Lipoprotein. AB - Glycation-induced high-density lipoprotein (HDL) modification by aldehydes can result in loss of its antiinflammatory/antioxidative properties, contributing to diabetes-associated cardiovascular diseases. Isoferulic acid, a major active ingredient of Cimicifuga heracleifolia, shows antiinflammatory, antiviral, antioxidant, and antidiabetic properties. Thus, this study investigated the antiglycation effect of isoferulic acid against compositional modifications of HDL and loss of biological activity of HDL-paraoxonase induced on incubation with different aldehydes. Protective effect of isoferulic acid was assessed by subjecting purified HDL from human plasma to glycation with methylglyoxal, glyoxal, or glycolaldehyde and varying concentrations of isoferulic acid. The effect of isoferulic acid was analyzed by determining amino group number, tryptophan and advanced glycation end-product fluorescence, thermal denaturation studies, carboxymethyl lysine content, and activity of HDL-paraoxonase. Concentration-dependent inhibitory action of isoferulic acid was observed against extensive structural perturbations, decrease in amino group number, increase in carboxymethyl lysine content, and decrease in the activity of HDL-paraoxonase caused by aldehyde-associated glycation in the HDL molecule. Isoferulic acid, when taken in concentration equal to that of aldehydes, was most protective, as 82-88% of paraoxonase activity was retained for all studied aldehydes. Isoferulic acid shows antiglycation action against aldehyde-associated glycation in HDL, which indicates its therapeutic potential for diabetic patients, especially those with micro-/macrovascular complications. PMID- 27262200 TI - Development of novel electrospun dual-drug fiber mats loaded with a combination of ampicillin and metronidazole. AB - OBJECTIVE: Our study was performed with the aim of preparing electrospun polylactide fibers with a combination of ampicillin (AMP) and metronidazole (MNZ) and investigating their drug release behavior and the antibacterial effect on Aggregatibacter actinomycetemcomitans and other oral pathogens. METHODS: AMP and MNZ were integrated as a combination in two separate fibers (dual fiber mats - DFW mix) of electrospun PLA fiber mats by means of multijet electrospinning and in a single fiber (single fiber mats - SFW mix). HPLC (high-performance liquid chromatography) was used to measure the released drug quantities. Agar diffusion tests were used to determine the antibacterial effect of the eluates on A. actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis and Enterococcus faecalis. The neutral red test was made to examine the cytocompatibility of the eluates with human gingival fibroblasts (hGFs). RESULTS: The release of the active agents varied with the antibiotic concentrations initially used in the fiber mats, but also with the distribution of the active agents in one or two fibers. Of the total quantity of MNZ (AMP), the SFW mix fiber mats released >60% (>70%) within a span of 5min, and 76% (71%) after 96h. With these drug concentrations released by the fiber mats (>=5m%), an antibacterial effect was achieved on A. actinomycetemcomitans and on all other species tested. Fiber mats and their eluates have no cytotoxic influence on human gingival fibroblasts (hGFs). SIGNIFICANCE: Electrospun AMP/MNZ-loaded polymer fibers are a potential drug delivery system for use in periodontal and endodontic infections. PMID- 27262201 TI - Development of a Support Vector Machine-Based System to Predict Whether a Compound Is a Substrate of a Given Drug Transporter Using Its Chemical Structure. AB - The aim of this study was to develop an in silico prediction system to assess which of 7 categories of drug transporters (organic anion transporting polypeptide [OATP] 1B1/1B3, multidrug resistance-associated protein [MRP] 2/3/4, organic anion transporter [OAT] 1, OAT3, organic cation transporter [OCT] 1/2/multidrug and toxin extrusion [MATE] 1/2-K, multidrug resistance protein 1 [MDR1], and breast cancer resistance protein [BCRP]) can recognize compounds as substrates using its chemical structure alone. We compiled an internal data set consisting of 260 compounds that are substrates for at least 1 of the 7 categories of drug transporters. Four physicochemical parameters (charge, molecular weight, lipophilicity, and plasma unbound fraction) of each compound were used as the basic descriptors. Furthermore, a greedy algorithm was used to select 3 additional physicochemical descriptors from 731 available descriptors. In addition, transporter nonsubstrates tend not to be in the public domain; we, thus, tried to compile an expert-curated data set of putative nonsubstrates for each transporter using personal opinions of 11 researchers in the field of drug transporters. The best prediction was finally achieved by a support vector machine based on 4 basic and 3 additional descriptors. The model correctly judged that 364 of 412 compounds (internal data set) and 111 of 136 compounds (external data set) were substrates, indicating that this model performs well enough to predict the specificity of transporter substrates. PMID- 27262202 TI - Design of an In Situ Cross-Linked Eutectic Tablet for Enhanced Delivery of Gastro Sensitive Proteins and Peptides. AB - In the present study, a eutectic platform was designed as an in situ cross-linked eutectic tablet for structural protection, enhanced intestinal permeation, and controlled release of proteins after oral administration. Physicochemical and physicomechanical analyses of the eutectic tablets were undertaken to elucidate the in situ cross-linking mechanism, thermal transitions, crystallinity, ex vivo permeation, and in vitro release of the protein. Following thermal characterization, results revealed successful eutectic formation with a melting point to 37 degrees C. Protein release from the formulation was controlled over 24 h with a maximum fractional release of +/-0.8 for all formulations. The release pattern alternated between phases of burst and slow release which was attributed to the combined effects of swelling, surface erosion, and in situ cross-linking. Mathematical modeling of the protein release kinetics corresponded best with the Higuichi model with near zero-order (R(2) ~ 0.9787) release. The permeation-enhancing effect of menthol contained within the eutectic powder blend was investigated and results showed an enhanced protein flux (0.0576-0.0720 mg.cm(-2) h(-1)) across the intestinal tissue model compared with a control formulation. Extensive in vitro characterization highlighted the successful design of the eutectic tablets as a potential oral delivery system for proteins with structural protection, enhanced intestinal permeation, and controlled release. PMID- 27262203 TI - Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms. AB - Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. PMID- 27262205 TI - An Overview of Pharmaceutical Excipients: Safe or Not Safe? AB - A medicine consists of 2 fundamental parts: the active pharmaceutical ingredient and the excipient. Most, if not all, medicines could not be made without the use of excipients. In the early times, the safety of excipients was overlooked and no specific safety tests were generally conducted. This fact has been changed over times and is currently being recognized that the excipient's toxicity is not negligible, because its direct interaction with the active pharmaceutical ingredient or between other excipients may occur, leading to a potential change in the relationship between effectiveness and toxicity. This review is intended to address the general status of the pharmaceutical excipients and to describe the safety assessment. As a summary, this review suggests the interest of simplifying the formulations as much as possible and the interest of reducing the number of excipients necessary to strictly meet the required functions. The risk/benefit ratio of an excipient should be always evaluated on the basis of not only its production and quality but also of its safety. Further research according to Good Manufacturing Practices, Guiding Principles in Toxicology Assessment, Good Laboratory Practices, and Good Distribution Practices requirements are needed and are fundamental for health safety, contributing to a comprehensive picture of this matter. PMID- 27262204 TI - Evaluation of Heavy-Chain C-Terminal Deletion on Product Quality and Pharmacokinetics of Monoclonal Antibodies. AB - Due to their potential influence on stability, pharmacokinetics, and product consistency, antibody charge variants have attracted considerable attention in the biotechnology industry. Subtle to significant differences in the level of charge variants and new charge variants under various cell culture conditions are often observed during routine manufacturing or process changes and pose a challenge when demonstrating product comparability. To explore potential solutions to control charge heterogeneity, monoclonal antibodies (mAbs) with native, wild-type C-termini, and mutants with C-terminal deletions of either lysine or lysine and glycine were constructed, expressed, purified, and characterized in vitro and in vivo. Analytical and physiological characterization demonstrated that the mAb mutants had greatly reduced levels of basic variants without decreasing antibody biologic activity, structural stability, pharmacokinetics, or subcutaneous bioavailability in rats. This study provides a possible solution to mitigate mAb heterogeneity in C-terminal processing, improve batch-to-batch consistency, and facilitate the comparability study during process changes. PMID- 27262207 TI - An Investigation Into Vortioxetine Salts: Crystal Structure, Thermal Stability, and Solubilization. AB - Three 1:1 salts containing vortioxetine (VOT), an orally antidepressant drug, and 3 aryl monoacids have been designed and successfully prepared by liquid-assisted grinding based on the DeltapKa rule. The C-O bond lengths (~1.25 A) in the COOH groups show that the proton transfer has occurred from aryl monoacid to piperazine N1 atom of vortioxetine in the crystal structures. Three salts feature cyclic [2 + 2] structural units through R(4)4 (12) N-H...O hydrogen bonding interactions which result in the remarkable thermal stabilities, and VOT-p aminobenzoic acid shows 2-dimensional framework by linking cyclic [2 + 2] units through additional hydrogen bonding interactions. The equilibrium solubility of VOT in VOT-p-aminobenzoic acid salt can be largely improved up to 0.50 mg/mL (about 450% above the free base) at 25 degrees C in water, which also accelerates the intrinsic dissolution rate. PMID- 27262206 TI - The Pro-inflammatory Cytokine Interleukin-6 Regulates Nanoparticle Transport Across Model Follicle-Associated Epithelium Cells. AB - The aim of this study was to investigate whether the pro-inflammatory cytokines improved the function of the cell monolayer model of the human follicle associated epithelium (FAE) of co-culture of Caco-2 cells on permeable filters with Raji B-cells underneath from the viewpoint of particle transport. Exposure to tumor necrosis factor-alpha resulted in an almost maintained epithelial integrity/paracellular permeability combined with an increased nanoparticle transport in a dose-dependent manner while the effects of interleukin (IL)-1beta were limited. Exposure to IL-6 significantly enhanced the nanoparticle transport with the limited disruption of the cell monolayer integrity. The addition of IL-6 or tumor necrosis factor-alpha to Caco-2 monolayers without Raji B-cells did not enhance nanoparticle transport. In our IL-6 treated FAE model, the nanoparticle transport almost disappeared at 4 degrees C or after the addition of 5-(N-ethyl-N isopropyl) amiloride, an inhibitor of macropinocytosis. Furthermore, IgA binding, presumably by a secretory IgA receptor, a marker of M-cells was observed on the apical side of our model FAE. These results indicate that the combined effect of IL-6 with unknown factors from Raji-B cells made the FAE model more functional with regard to nanoparticle transport. The IL-6 enhanced FAE model will be a useful platform for nanoparticle drug delivery research across the intestinal epithelium. PMID- 27262209 TI - Subgingival microbiota in individuals with severe chronic periodontitis. AB - BACKGROUND/PURPOSE: Subgingival microorganisms are potentially associated with periodontal diseases. However, the correlation between the variance in the periodontal microbiome and the prevalence and severity of periodontitis remains unclear. The aim of this study was to determine the subgingival microbiota in Taiwanese individuals with severe chronic periodontitis (SP). METHODS: The composition of the subgingival microbiota in healthy and diseased individuals was compared using a 16S rRNA metagenomic approach and quantitative polymerase chain reaction (qPCR). A total of 20 samples, including 10 from healthy individuals and 10 from SP patients, were analyzed. RESULTS: We found high microbial diversity, with an average of 774 classified phylotypes per sample and a total of six bacterial phyla across all samples. Cluster analysis by principal component analysis and heat map showed that the bacterial communities were different in the two groups. Streptococcus dominated across all the healthy samples, whereas Prevotella, Porphyromonas, and Treponema were highly abundant across all diseased samples. At least 13 bacterial genera were conserved among all the samples. Only eight genera, including Lautropia, Parvimonas, Actinomyces, Capnocytophaga, Paludibacter, Streptococcus, Haemophilus, and Corynebacterium, were significantly enriched in the healthy group, and six genera, including Porphyromonas, Treponema, Tannerella, Aggregatibacter, Peptostreptococcus, and Filifactor, were significantly enriched in the diseased group. Furthermore, a trend of abundance of bacteria at the species level measured by qPCR in all samples was consistent with the 16S rRNA metagenomics results. CONCLUSION: This study is the first in Taiwan to provide a picture of the microbiome in SP via 16S rRNA metagenomics. PMID- 27262208 TI - Bio-Kil, a nano-based disinfectant, reduces environmental bacterial burden and multidrug-resistant organisms in intensive care units. AB - BACKGROUND/PURPOSE: This prospective before-after study was intended to investigate the effect of Bio-Kil on reducing environmental bacterial burden and healthcare-associated infections (HAIs) in intensive care units (ICUs) at the Municipal Wan-Fang Hospital, Taipei, Taiwan in 2014. METHODS: Four rooms in the medical and surgical ICUs were investigated and designated as study rooms (n = 2) or control rooms (n = 2). Routine disinfection was performed during the pre intervention period in both room types. Bio-Kil was applied to the fomites and surroundings of the study rooms during the intervention period. Total bacterial burden and proportion of colonization of fomites and surroundings by multidrug resistance organisms (MDROs) were determined before and after the intervention. The demographic characteristics, underlying conditions, and clinical outcomes of patients were analyzed. RESULTS: After application of Bio-Kil, the bacterial burden declined in both groups, although the reduction was greater in the study rooms as compared with the control rooms (p = 0.001). During the pre-intervention period, 16 patients were admitted to control rooms and 18 patients to study rooms. After the intervention, 22 patients were admitted to control rooms and 21 patients to study rooms. The number of cases of new-onset sepsis declined in the intervention group (from 33% to 23.8%), but increased in the control group (from 25% to 40.9%); however, there was no significant difference in incidence of new onset sepsis between the study and control rooms after intervention. CONCLUSION: Application of Bio-Kil reduced the environmental bacterial burden and MDROs in ICUs. Further studies are needed to evaluate the efficacy of this nanotechnology based disinfectant in reducing HAIs. PMID- 27262210 TI - Rapid identification of Streptococcus intermedius by multiplex polymerase chain reaction 1 week before culture positivity in a patient with antibiotic-treated thalamic brain abscess. PMID- 27262211 TI - Toward sustainable and effective control: Experience of China Ebola Treatment Center in Liberia. PMID- 27262213 TI - Asymmetric ground reaction forces and knee kinematics during squat after anterior cruciate ligament (ACL) reconstruction. AB - BACKGROUND: This bilateral squat study tests whether people with anterior cruciate ligament (ACL) reconstruction have symmetric three-dimensional ground reaction forces (GRFs) and symmetric anterior-posterior (AP) translation rates of the femur with respect to the tibia when compared with healthy control subjects. We hypothesized that there would be no long-term asymmetry in knee kinematics and kinetics in ACL reconstructed subjects following surgery and rehabilitation. METHODS: Position and GRF data were collected on eight ACL reconstructed and eight control subjects during bilateral squat. The rate of relative AP translation was determined for each subject. Principal component models were developed for each of the three GRF waveforms. Principal component scores were used to assess symmetry within the ACL reconstructed group and within the control group. RESULTS: ACL reconstructed knees analyzed in early flexion during squat descent displayed a four-fold greater rate of change in anterior translation in the reconstructed knee relative to the contralateral side than did a similar comparison of normal knees. Differences were found between the ACL reconstructed subjects' injured and uninjured limbs for all GRFs. CONCLUSIONS: Subjects following ACL reconstruction had asymmetric GRFs and relative rates of AP translation at an average of seven years after ACL reconstructive surgery when compared with control subjects. CLINICAL RELEVANCE: These alterations in loading may lead to altered load distributions across the knee joint and may put some subjects at risk for future complications such as osteoarthritis. PMID- 27262212 TI - Identifying the Appropriate FISH Criteria for Defining MET Copy Number-Driven Lung Adenocarcinoma through Oncogene Overlap Analysis. AB - INTRODUCTION: Mesenchymal-epithelial transition factor gene (MET) gene copy number gain may be a predictive biomarker for mesenchymal-epithelial transition factor (MET) inhibition in lung cancer, but the most appropriate method and criteria for defining MET positivity are uncertain. METHODS: MET copy number was assessed by fluorescence in situ hybridization in lung adenocarcinoma. Positivity criteria included mean MET per cell values greater than 5 (low [>=5 to <6], intermediate [>=6 to <7], and high [>=7]) and mean MET-to-chromosome 7 centromere ratios (MET/CEP7) of at least 1.8 (low [>=1.8 to <=2.2], intermediate [>2.2 to <5], and high [>=5]). Associated clinical and molecular characteristics were captured. RESULTS: Of 686 cases, 99 (14%) had a mean MET per cell value of 5 or greater, 52 of 1164 (4.5%) had a MET/CEP7 ratio of 1.8 or higher. Other oncogenic drivers (in EGFR, KRAS, anaplastic lymphoma receptor tyrosine kinase gene [ALK], erb-b2 receptor tyrosine kinase 2 gene [ERBB2], BRAF, NRAS, ROS1, or ret proto oncogene [RET]) were detectable in 56% of the group with a mean MET per cell value of 5 or higher and 47% of the group with a MET/CEP7 ratio of 1.8 or higher, suggesting that many MET-positive cases are not truly MET addicted. The rates of concomitant drivers in the groups of patients in the low, indeterminate, and high categories of mean MET per cell were 32 of 52 (62%), 12 of 19 (63%), and 11 of 27 (41%) (p = 0.2), and the rates of concomitant drivers in the low, intermediate, and high categories of MET/CEP7 ratios were 15 of 29 (52%), 9 of 18 (50%), and 0 of 4 (0%), respectively (p = 0.04). A MET/CEP7 ratio of 1.8 or higher in the absence of other oncogenes was associated with a higher rate of adrenal metastases (p = 0.03) but not with never-smoking status. CONCLUSIONS: A fluorescence in situ hybridization MET/CEP7 ratio of 5 or higher defined a "MET positive" group with no oncogenic overlap. As this method and criteria are also associated with the highest response rate to MET inhibition, it represents the clearest definition of a MET copy number gain-addicted state. However, a MET associated phenotype may also exist across cases with a MET/CEP7 of 1.8 or higher when no other oncogene overlap occurs. PMID- 27262214 TI - Reduction of dioxin-like toxicity in effluents by additional wastewater treatment and related effects in fish. AB - Efficiency of advanced wastewater treatment technologies to reduce micropollutants which mediate dioxin-like toxicity was investigated. Technologies compared included ozonation, powdered activated carbon and granular activated carbon. In addition to chemical analyses in samples of effluents, surface waters, sediments, and fish, (1) dioxin-like potentials were measured in paired samples of effluents, surface waters, and sediments by use of an in vitro biotest (reporter gene assay) and (2) dioxin-like effects were investigated in exposed fish by use of in vivo activity of the mixed-function, monooxygenase enzyme, ethoxyresorufin O-deethylase (EROD) in liver. All advanced technologies studied, based on degradation or adsorption, significantly reduced dioxin-like potentials in samples and resulted in lesser EROD activity in livers of fish. Results of in vitro and in vivo biological responses were not clearly related to quantification of targeted analytes by use of instrumental analyses. PMID- 27262215 TI - Sub-lethal effects of cadmium and copper on RNA/DNA ratio and energy reserves in the green-lipped mussel Perna viridis. AB - This study aims to test if RNA/DNA ratio and various energy reserve parameters (i.e., glycogen, lipid, protein content and total energy reserves) are sensitive biomarkers for indicating stresses induced by metal contaminants in the green lipped mussel Perna viridis, a common organism for biomonitoring in Southeast Asia. This study was, therefore, designed to examine the effects of cadmium (Cd) and copper (Cu) on these potential biomarkers in two major energy storage tissues, adductor muscle (AM) and hepatopancreas (HP), of P. viridis after sub lethal exposure to either metal for 10 days. The results showed that neither Cd nor Cu treatments affected the RNA/DNA ratio, glycogen and protein contents in AM and HP. As the most sensitive biomarker in P. viridis, the total lipid content in both AM and HP was significantly decreased in the treatment of 5MUg Cu/L and 0.01 0.1MUgCd/L, respectively. However, soft-tissue body burdens of Cu or Cd did not significantly correlate with each of the four biomarkers regardless of the tissue type. In addition, AM generally stored more glycogen than HP, whereas HP stored more lipids than AM. We proposed that multiple biomarkers may be employed as an integrated diagnostic tool for monitoring the health condition of the mussels. PMID- 27262217 TI - Cognitive functions and cerebral oxygenation changes during acute and prolonged hypoxic exposure. AB - The present study aimed to assess specific cognitive processes (cognitive control and time perception) and hemodynamic correlates using functional near-infrared spectroscopy (fNIRS) during acute and prolonged high-altitude exposure. Eleven male subjects were transported via helicopter and dropped at 14 272 ft (4 350 meters) of altitude where they stayed for 4 days. Cognitive tasks, involving a conflict task and temporal bisection task, were performed at sea level the week before ascending to high altitude, the day of arrival (D0), the second (D2) and fourth (D4) day at high altitude. Cortical hemodynamic changes in the prefrontal cortex (PFC) area were monitored with fNIRS at rest and during the conflict task. Results showed that high altitude impacts information processing in terms of speed and accuracy. In the early hours of exposure (D0), participants displayed slower reaction times (RT) and decision errors were twice as high. While error rate for simple spontaneous responses remained twice that at sea level, the slow down of RT was not detectable after 2 days at high-altitude. The larger fNIRS responses from D0 to D2 suggest that higher prefrontal activity partially counteracted cognitive performance decrements. Cognitive control, assessed through the build-up of a top-down response suppression mechanism, the early automatic response activation and the post-error adjustment were not impacted by hypoxia. However, during prolonged hypoxic exposure the temporal judgments were underestimated suggesting a slowdown of the internal clock. A decrease in cortical arousal level induced by hypoxia could consistently explain both the slowdown of the internal clock and the persistence of a higher number of errors after several days of exposure. PMID- 27262216 TI - Effect of ruthenium red, a ryanodine receptor antagonist in experimental diabetes induced vascular endothelial dysfunction and associated dementia in rats. AB - Diabetes mellitus is considered as a main risk factor for vascular dementia. In the past, we have reported the induction of vascular dementia by experimental diabetes. This study investigates the efficacy of a ruthenium red, a ryanodine receptor antagonist and pioglitazone in the pharmacological interdiction of pancreatectomy diabetes (PaD) induced vascular endothelial dysfunction and subsequent vascular dementia in rats. Attentional set shifting and Morris water maze test were used for assessment of learning and memory. Vascular endothelial function, blood brain barrier permeability, serum glucose, serum nitrite/nitrate, oxidative stress (viz. aortic superoxide anion, brain thiobarbituric acid reactive species and brain glutathione), brain calcium and inflammation (myeloperoxidase) were also estimated. PaD rats have shown impairment of endothelial function, blood brain barrier permeability, learning and memory along with an increase in brain inflammation, oxidative stress and calcium. Administration of ruthenium red and pioglitazone has significantly attenuated PaD induced impairment of learning, memory, blood brain barrier permeability, endothelial function and biochemical parameters. It may be concluded that ruthenium red, a ryanodine receptor antagonist and pioglitazone, a PPAR-gamma agonist may be considered as potent pharmacological agent for the management of PaD induced endothelial dysfunction and subsequent vascular dementia. Ryanodine receptor may be explored further for their possible benefits in vascular dementia. PMID- 27262218 TI - Terminal differentiation induction as DNA damage response in hematopoietic stem cells by GADD45A. AB - Hematopoietic stem cells (HSCs) sustain lifelong blood cell regeneration by balancing their ability for self-renewal with their ability to differentiate into all blood cell types. To prevent organ exhaustion and malignant transformation, long-lived HSCs, in particular, must be protected from exogenous and endogenous stress, which cause severe DNA damage. When DNA is damaged, distinct DNA repair mechanisms and cell fate controls occur in adult HSCs compared with committed cells. Growth arrest and DNA damage-inducible 45 alpha (GADD45A) is known to coordinate a variety of cellular stress responses, indicating the molecule is an important stress mediator. So far, the function of GADD45A in hematopoietic stem and progenitor cells is controversial and appears highly dependent on the cell type and stress stimulus. Recent studies have analyzed its role in cell fate decision control of prospectively isolated HSCs and have revealed unexpected functions of GADD45A, as discussed here. The upregulation of GADD45A by DNA damage-causing conditions results in enhanced HSC differentiation, probably to efficiently eliminate aberrant HSCs from the system. These findings, in concert with a few studies on other stem cell systems, have led us to propose DNA damage induced differentiation as a novel DNA damage response mechanism in stem cells that circumvents the fatal consequences of cumulative DNA damage in the stem cell compartment. PMID- 27262219 TI - Transposition of lingual thyroid gland to the submandibular region by transoral approach. AB - The purpose of this case report is to demonstrate surgical technique of only functional but symptomatic lingual thyroid gland transposition to submandibular region by transoral approach without mandibulotomy and tongue-splitting. A 37 year-old female patient was admitted to our hospital with dysphagia and apnea symptoms. Physical examination revealed 3cm*3cm lingual thyroid gland was detected at the tongue base. The patient was euthyroid and thyroid gland was not detected in the neck. Under general anesthesia, right submandibular gland excision and transposition of lingual thyroid tissue to submandibular region with dorsal lingual artery axis flap were performed by transoral approach. Thyroid hormones remained normal in the postoperative period. In conclusion transoral transposition of lingual thyroid to submandibular region as a flap without mandibulotomy is a minimally invasive and function preserving alternative approach. Besides preserving thyroid functions, this transoral surgical technique can be preferred by patients who avoid skin incision for esthetic concerns. PMID- 27262221 TI - Endoscopic cartilage butterfly myringoplasty in children. AB - OBJECTIVE: The present study evaluated the results of the graft success rate and hearing gain of children who underwent endoscopic inlay butterfly myringoplasty due to chronic otitis media. METHODS: The study included 32 pediatric patients aged between 8 and 17, who had endoscopic inlay butterfly myringoplasty with the diagnosis of chronic otitis media between September 2012 and January 2015 in Elazig Training and Research Hospital Otorhinolaryngology Clinic and Firat University Otorhinolaryngology Clinic. All patients' demographics, perforation size, and hearing status were examined. RESULTS: Tympanic membrane perforation was <=3mm in 12 patients and between 3 and 6mm in 20 patients. The air-bone gap (ABG) of the patients was 18.5+/-6.29dB preoperatively, 8.81+/-3.53dB postoperatively second month, 8.09+/-3.55dB postoperatively sixth month, and 7.96+/-3.32dB postoperatively 12th month. Two (6.3%) of the patients had postoperative myringitis. Two (6.3%) patients had recurrent perforation in the postoperative follow-ups. CONCLUSION: In children, endoscopic inlay butterfly tympanoplasty is a surgical technique with short duration, high graft success, effective hearing reconstruction, and high levels of postoperative patient comfort. PMID- 27262220 TI - Laryngeal myofascial pain syndrome as a new diagnostic entity of dysphonia. AB - OBJECTIVE: To consider the feasibility of diagnosing intrinsic laryngeal muscle myofascial pain syndrome (MPS) in dysphonic patients who demonstrated immediate symptom and stroboscopic finding improvement after laryngeal electromyography (LEMG) without further treatment. METHODS: A chart review of patients who showed subtle vocal fold movement abnormalities on a stroboscopic examination and underwent ultrasonography (US)-guided LEMG was performed. Patients with vocal fold paralysis, mucosal lesions, spasmodic dysphonia, and vocal tremor on stroboscopic examination were excluded. Among them, patients with normal EMG findings were included in this study. The patients who reported voice symptom improvement after LEMG without further treatment were placed in laryngeal MPS (LMPS) group and the other patients were placed in non-laryngeal MPS (non-MPS) group. Predisposing factors, voice symptom, symptom-duration, and stroboscopic findings of these patients were reviewed. RESULTS: Among the 16 patients, LEMG findings were normal, five (31%) were included in the LMPS group and the other 11 patients (69%) were included in the non-MPS group. All LMPS group patients had a history of voice abuse and reported odynophonia. The Korean Voice Handicap Index 10 score decreased significantly after US-guided LEMG without additional treatment in the LMPS group. The stroboscopic findings revealed that vocal fold hypomobility was the most common finding in the LMPS group, and two patients showed a muscle tension dysphonia pattern. The LMPS groups showed improvement of vocal fold mobility on 1-week stroboscopic evaluation. CONCLUSION: LMPS is a potential diagnosis for patients with vocal fold hypomobility finding on stroboscopic findings but with normal EMG results. Diagnosis of LMPS could be considered in patients who showed symptom and vocal fold movement improvement after LEMG. PMID- 27262222 TI - Modulating the endometrial epithelial proteome and secretome in preparation for pregnancy: The role of ovarian steroid and pregnancy hormones. AB - Dialogue between an appropriately developed embryo and hormonally-primed endometrium is essential to achieve implantation and establish pregnancy. Importantly, the point-of-first-contact between the embryo and the maternal endometrium occurs at the endometrial luminal epithelium (LE). Implantation events occur within the uterine cavity microenvironment regulated by local factors. Defects in embryo-endometrial communication likely underlie unexplained infertility; enhanced knowledge of this communication, specifically at initial maternal-fetal contact may reveal targets to improve fertility. Using a human endometrial luminal-epithelial (LE) cell line (ECC1), this targeted proteomic study reveals unique protein changes in both cellular (98% unique identifications) and secreted (96% unique identifications) proteins in the transition to the progesterone-dominated secretory (receptive) phase and subsequently to pregnancy, mediated by embryo-derived human chorionic gonadotropin (hCG). This analysis identified 157 progesterone-regulated cellular proteins, with further 193 significantly altered in response to hCG. Cellular changes were associated with metabolism, basement membrane and cell connectivity, proliferation and differentiation. Secretome analysis identified 1059 proteins; 123 significantly altered by progesterone, and 43 proteins altered by hCG, including proteins associated with cellular adhesion, extracellular-matrix organization, developmental growth, growth factor regulation, and cell signaling. Collectively, our findings reveal dynamic intracellular and secreted protein changes in the endometrium that may modulate successful establishment of pregnancy. BIOLOGICAL SIGNIFICANCE: This study provides unique insights into the developmental biology of embryo implantation using targeted proteomics by identifying endometrial epithelial cellular and secreted protein changes in response to ovarian steroid hormones and pregnancy hormones that are essential for receptivity and implantation. PMID- 27262224 TI - Opioids and Sleep-Disordered Breathing. AB - Opioid use for chronic pain analgesia, particularly chronic noncancer pain, has increased greatly since the late 1990s, resulting in an increase in opioid associated morbidity and mortality. A clear link between opioid use and sleep disordered breathing (SDB) has been established, with the majority of chronic opioid users being affected by the condition, and dose-dependent severity apparent for some opioids. More evidence is currently needed on how to effectively manage opioid-induced SDB. This review summarizes the current state of knowledge relating to management of patients undergoing chronic opioid therapy who have SDB. Initial management of these patients requires a thorough biopsychosocial assessment of their need for opioid therapy, consideration of reduction or cessation of the opioid if possible, and analysis of alternative therapies for treatment of their pain. If opioid therapy must be continued, then management of the associated SDB may be important. Several small- to medium-scale studies have examined the efficacy of noninvasive ventilation, particularly adaptive servo-ventilation (ASV) for the treatment of opioid-associated SDB. This research is particularly important because opioids predispose predominantly to central sleep apnea and also, to a lesser extent, OSA. Generally, these studies have found positive results in treating opioid-associated SDB with ASV in terms of improving outcome measures such as central apnea index and the apnea-hypopnea index. Larger studies that measure longer term health outcomes, patient sleepiness, and compliance are needed, however. Registries of health outcomes of ASV-treated patients may assist with future treatment planning. PMID- 27262223 TI - A proteomic road to acquire an accurate serological diagnosis for human tegumentary leishmaniasis. AB - : Diagnostic tools are important for clinical management and epidemiological evaluation of Tegumentary (TL) and Visceral (VL) Leishmaniasis. Serology is not frequently used for the diagnosis of the TL form because low antibody titers and cross-reaction with VL. Therefore, it is crucial to identify specific and immunogenic antigens from species associated with the TL form. Here we employed a proteomic approach coupled to an in silico analysis and identified the most abundant and immunogenic proteins from Leishmania amazonensis, Leishmania braziliensis and Leishmania infantum. Of 16 species specific proteins, nine were from the species causative of the TL form (L. amazonensis and L. braziliensis). In silico analysis revealed 18 B-cell epitopes with 0% similarity to Trypanosoma cruzi orthologs and, therefore, less likely to crossreact with sera of patients with Chagas disease. Two proteins reacted exclusively with serum from TL patients and presented several B-cell epitopes without similarity to T. cruzi orthologs: the hypothetical protein GI 134063939 and the metallo-peptidase Clan MA(E)-Family M3. The immunoassay revealed nine peptides with strong reactivity to sera from TL patients. These proteins and peptides may be good candidates to improve the specificity and sensibility of serological tests aiming to diagnose the TL of this neglected human disease. BIOLOGICAL SIGNIFICANCE: As no gold-standard test for tegumentary leishmaniasis (TL) exists, a combination of different diagnostic techniques is often necessary to obtain precise results. Thus, the identification of species-specific, highly immunogenic and abundant proteins that stimulate the humoral immune response in the host should help in the development of serological tests for human TL. Herein we searched for these potential antigens in Leishmania species related to American Leishmaniasis (L. amazonensis, L. braziliensis and L. infantum). To this end, we employed an immunoproteomic approach using proteins from these Leishmania species and sera from TL and Visceral Leishmaniasis (VL) patients. Our study unveils specific proteins and peptides that may represent antigens that will help the efforts to improve the accuracy of serological tests to diagnose the TL form. PMID- 27262225 TI - Long-term Anticoagulation With Rivaroxaban for Preventing Recurrent VTE: A Benefit-Risk Analysis of EINSTEIN-Extension. AB - BACKGROUND: Short-term anticoagulant treatment for acute DVT or pulmonary embolism (PE) effectively reduces the risk of recurrent disease during the first 6 to 12 months of therapy. Continued anticoagulation often is not instituted because of the perception among physicians that the risk of major bleeding will outweigh the risk of new venous thrombotic episodes. METHODS: The authors performed a benefit-risk analysis by using the randomized EINSTEIN-Extension trial, which compared continued rivaroxaban with placebo in 1,197 patients with symptomatic DVT or PE who had completed 6 to 12 months of anticoagulation and in whom physicians had equipoise with respect to the need for continued anticoagulation. One-year Kaplan-Meier rates and rate differences of recurrent VTE and major bleeding were calculated. Benefits and risks were assessed using rate differences scaled to a population size of 10,000 patients treated for 1 year. RESULTS: Recurrent VTE occurred in eight recipients of rivaroxaban and 42 patients receiving placebo. In a population of 10,000 patients treated for 1 year, rivaroxaban treatment would have resulted in 665 (95% CI, 246-1,084) fewer recurrent VTEs than would placebo (number needed to treat = 15). Major bleeding occurred in four (0.7%) and zero patients, respectively. Rivaroxaban treatment would have resulted in 68 (95% CI, 2-134) more major bleeding events than would placebo (number needed to harm = 147). Kaplan-Meier analysis showed early recurrent VTE reduction with rivaroxaban that continued to improve throughout treatment; major bleeding increased gradually, plateauing at approximately 100 days. CONCLUSIONS: A clinically important benefit and a favorable benefit-risk profile of continued rivaroxaban anticoagulation was observed. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00439725; URL: www.clinicaltrials.gov. PMID- 27262226 TI - Determinants of Smoking Cessation in Patients With COPD Treated in the Outpatient Setting. AB - BACKGROUND: The beneficial effects of smoking cessation on the progression of COPD are well established. Nevertheless, many patients with COPD continue to smoke. METHODS: In this nationwide hospital-based prospective follow-up study, we examined rates of smoking cessation and clinical and sociodemographic determinants of smoking cessation in 3,233 patients with COPD who smoked on outpatient contact during 2008 to 2012. Using multivariate Cox regression, we calculated hazard ratios (HRs) of quitting. RESULTS: Within 1 and 5 years from first outpatient contact, the probability of quitting was 19% and 45%, respectively. In adjusted analyses, patients were less likely to quit if they were younger, with an HR of 0.84 (95% CI, 0.71-0.99) for patients aged 50 to 69 years and 0.53 (95% CI, 0.37-0.76) for patients aged 30 to 49, compared with those aged 70 years or older, who had lower income (HR, 0.79; 95% CI, 0.67-0.94), lived alone (HR, 0.75; 95% CI, 0.64-0.88), were unemployed (HR, 0.70; 95% CI, 0.54-0.90), had milder COPD with an HR of 0.67 (95% CI, 0.53-0.84) for Global Initiative for Chronic Obstructive Lung Disease (GOLD) A and 0.61 (95% CI, 0.47 0.80) for GOLD B compared with GOLD D, had Medical Research Council (MRC) dyspnea scale score < 4 (HR 0.80, 95% CI 0.68-0.95), or no history of exacerbations treated on an outpatient basis. (HR, 0.80; 95% CI, 0.68-0.93). CONCLUSIONS: These findings reinforce that young and socioeconomically disadvantaged patients have more difficulties achieving timely smoking cessation. A novel finding is that patients with milder COPD are less likely to quit. The findings suggest a need for interventional studies focusing on these subgroups to ensure abstinence to halt disease progression. PMID- 27262227 TI - Risks of Venous Thromboembolism After Cesarean Sections: A Meta-Analysis. AB - BACKGROUND: Cesarean sections (CS) are believed to be associated with greater risks of postpartum VTE. Our objective was to systematically review the evidence on this association and on the absolute risk of VTE following CS. METHODS: We searched PubMed, Embase, and conference proceedings from 1980 to November 2015 for reports on the associations of delivery methods with postpartum VTE and on the incidence of VTE following CS. Studies on thrombophilia or recurrent VTE were excluded, and the search was restricted to prospective studies when assessing the incidence of VTE. Pooled relative and absolute risks were estimated with random effects models. RESULTS: The search retrieved 28 mostly retrospective observational studies comparing risks of VTE following CS and following vaginal deliveries (VD) (> 53,000 VTE events) and 32 prospective studies reporting risks of VTE following CS (218 VTE events). Compared with VD, the relative risk of VTE following CS ranged from 1 to 22, with a meta-analytic OR of 3.7 (95% CI, 3.0 4.6). Adjustment for age and BMI had a marginal influence on the estimated pooled OR. Associations were observed for both elective and emergency CS, with stronger estimates of associations for emergency CS. The pooled incidence was 2.6 VTE per 1,000 CS (95% CI, 1.7-3.5) and was greater in studies with a longer and better follow-up in the postpartum period (4.3 per 1,000 CS). CONCLUSIONS: The risk of VTE was fourfold greater following CS than following VD; seemed independent of other VTE risk factors; and was greater following emergency CS than following elective CS. On average, three in 1,000 women will develop a VTE following CS. PMID- 27262228 TI - Commentary regarding Schayek et al., entitled "The rate of recurrent BRCA1, BRCA2, and TP53 mutations in the general population, and unselected ovarian cancer cases, in Belo Horizonte, Brazil". PMID- 27262229 TI - [Management of gastrinoma]. AB - Gastrinoma is a very rare tumor leading to gastrin hypersecretion and characterised by Zollinger-Ellisson syndrome (ZES) i.e. severe gastric and duodenal ulceration and profuse diarrhea. This disease can be sporadic or familial within a multiple endocrine neoplasia type 1 (MEN-1) syndrome. Diagnosis is based on hypergastrinemia/hypercholrhydria. Tumors are usually located in the duodeno-pancreas. Preoperative tumor location by CT, echoendoscopy and fibroscopy is not always possible because of the small size of the lesion that are frequently multiple. The aim of gastrinoma treatment is 1/to control the hormonal hypersecretion 2/to remove the neoplasm when it is possible. Surgery is the only chance to cure. Gastrinoma is a slow-growing tumor, and overall survival is good with a median survival above 10years and a 5-year survival above 80 % in surgically resected patients. Recurrence is frequent, a biochemical recurrence is observed in 65 % of cases and morphological recurrence in 40 % of patients at 2years. Metastases are associated with a dismal prognosis. PMID- 27262230 TI - Mathematical analysis of multi-antibiotic resistance. AB - BACKGROUND: Multi-antibiotic resistance in bacterial infections is a growing threat to public health. Some experiments were carried out to study the multi antibiotic resistance. METHODS: The changes of the multi-antibiotic resistance with time were achieved by numerical simulations and the mathematical models, with the calculated temperature field, velocity field, and the antibiotic concentration field. RESULTS: The computed results and experimental results are compared. CONCLUSIONS: Both numerical simulations and the analytic models suggest that minor low concentrations of antibiotics could induce antibiotic resistance in bacteria. PMID- 27262231 TI - Accuracy of remote chest X-ray interpretation using Google Glass technology. AB - OBJECTIVES: We sought to explore the accuracy of remote chest X-ray reading using hands-free, wearable technology (Google Glass, Google, Mountain View, California). METHODS: We compared interpretation of twelve chest X-rays with 23 major cardiopulmonary findings by faculty and fellows from cardiology, radiology, and pulmonary-critical care via: (1) viewing the chest X-ray image on the Google Glass screen; (2) viewing a photograph of the chest X-ray taken using Google Glass and interpreted on a mobile device; (3) viewing the original chest X-ray on a desktop computer screen. One point was given for identification of each correct finding and a subjective rating of user experience was recorded. RESULTS: Fifteen physicians (5 faculty and 10 fellows) participated. The average chest X-ray reading score (maximum 23 points) as viewed through the Google Glass, Google Glass photograph on a mobile device, and the original X-ray viewed on a desktop computer was 14.1+/-2.2, 18.5+/-1.5 and 21.3+/-1.7, respectively (p<0.0001 between Google Glass and mobile device, p<0.0001 between Google Glass and desktop computer and p=0.0004 between mobile device and desktop computer). Of 15 physicians, 11 (73.3%) felt confident in detecting findings using the photograph taken by Google Glass as viewed on a mobile device. CONCLUSION: Remote chest X ray interpretation using hands-free, wearable technology (Google Glass) is less accurate than interpretation using a desktop computer or a mobile device, suggesting that further technical improvements are needed before widespread application of this novel technology. PMID- 27262232 TI - Corrigendum to "The influence of androstadienone during psychosocial stress is modulated by gender, trait anxiety and subjective stress: An fMRI study" [Psychoneuroendocrinology 68 (2016) 126-139]. PMID- 27262233 TI - Preparation of a partially carboxymethylated cotton gauze and study of its hemostatic properties. AB - In this study, we attempted to modify cotton gauze by partial carboxymethylation by varying the reaction time and concentration of monochloroacetic acid and sodium hydroxide. For each experiment, the relative value of the degree of substitution (DS) of the modified cotton gauze was evaluated and the whole blood clotting time (WBCT) and water absorption property were compared with cotton gauze and Surgicel. This revealed that, following an initial decrease, WBCT gradually increased. Using rabbit ear artery and liver haemorrhage models, the performance of the optimal modified gauze was compared to that of Surgicel and unmodified cotton gauze. The average bleeding times in the presence of modified cotton gauze in the rabbit ear arteries and the liver were 51.7s and 60.6s, while those with Surgicel and the unmodified cotton gauze were 76.8s and 95.5s, and 93.2s and 129.2s, respectively. The hemostatic and biocompatibility properties were evaluated using in vivo degradation experiments. This revealed that the modified gauze and Surgicel were totally degraded within 6 weeks. PMID- 27262234 TI - ErbB receptors and tetraspanins: Casting the net wider. PMID- 27262235 TI - Tamoxifen-induced cytotoxicity in breast cancer cells is mediated by glucose regulated protein 78 (GRP78) via AKT (Thr308) regulation. AB - Glucose regulated protein 78 (GRP78) has recently been suggested to be associated with drug resistance in breast cancer patients. However, the precise role of GRP78 in drug resistance and the involved signaling pathways are not clearly understood. In the present study, we show that among a panel of drugs, namely Paclitaxel (TAX), Doxorubicin (DOX), 5-fluorouracil (5-FU), UCN-01 and Tamoxifen (TAM) used, TAM alone up-regulated the expression of GRP78 significantly and induced apoptosis in MCF-7 and MDA-MB-231 cells. Interestingly, inhibition of GRP78 by a specific pharmacological inhibitor, VER-155008 augmented TAM-induced apoptosis, and overexpression of GRP78 rendered the cells resistant to TAM induced cell death suggesting a role for GRP78 in TAM-induced cytotoxicity. Mechanistically, the expression of phosphorylated AKT as determined by Western blot analyses revealed that TAM selectively upregulated phosphorylation of AKT at Thr308 but not at Ser473, and siRNA silencing of GRP78 resulted in inhibition of AKT phosphorylation at Thr308 but not at Ser473. Further, a GRP78 inhibitor, VER155008 inhibited TAM-induced phosphorylation of GSK3beta, a downstream substrate of AKT. These results, thus suggests a role for GRP78 in TAM-induced AKT activation. Additionally, co-localization studies by immunofluorescence, and immunoprecipitation experiments demonstrated a complex formation of AKT and GRP78. Furthermore, in glucose-free medium, the cells were sensitized to TAM induced cell death that was associated with reduced AKT phosphorylation at Thr308, thus strengthening the association of AKT regulation with drug response. Collectively, our findings identify a role of GRP78 in AKT regulation in response to TAM in breast cancer cells. PMID- 27262236 TI - Partial ileal bypass affords protection from onset of type 2 diabetes. AB - BACKGROUND: Partial ileal bypass (PIB) in the National Institutes of Health sponsored Program on the Surgical Control of the Hyperlipidemias (POSCH) randomized controlled trial was found to reduce plasma cholesterol, in particular low density lipoprotein cholesterol, with concomitant retardation of atherosclerotic cardiovascular disease and increased life expectancy. Glucagon like peptide-1, related to amelioration of type 2 diabetes, is increased over 5 fold after PIB. We hypothesized that PIB, in addition to its action on cholesterol metabolism, may also prevent type 2 diabetes. METHODS: We surveyed by telephone inquiry of former POSCH patients the 30+year posttrial incidence of type 2 diabetes or prediabetes, the presence of which was a trial exclusion criteria. We were able to contact 17.4% (n = 838) of the original POSCH population. RESULTS: Of 66 control responders, 17 contracted type 2 diabetes (25.8%); of 80 PIB responders, 8 contracted type 2 diabetes (10%). The difference between groups was significant (P = .015 by Fisher exact test) with an odds ratio of .320 for the PIB group and an over 2-fold (2.6) increase in the incidence of type 2 diabetes in the controls. Including borderline type 2 diabetes (prediabetic) patients, these values were 22 of 66 controls (33.3%) and 10 of 80 PIB patients (12.5%), with an odds ratio of .286 and a P<.004, and again an over 2-fold (2.7) increase in the incidence of type 2 diabetes in the control patients. CONCLUSION: PIB appears to afford partial protection from the onset of type 2 diabetes for over 30 years. PMID- 27262237 TI - Geographic and temporal validity of prediction models: different approaches were useful to examine model performance. AB - OBJECTIVE: Validation of clinical prediction models traditionally refers to the assessment of model performance in new patients. We studied different approaches to geographic and temporal validation in the setting of multicenter data from two time periods. STUDY DESIGN AND SETTING: We illustrated different analytic methods for validation using a sample of 14,857 patients hospitalized with heart failure at 90 hospitals in two distinct time periods. Bootstrap resampling was used to assess internal validity. Meta-analytic methods were used to assess geographic transportability. Each hospital was used once as a validation sample, with the remaining hospitals used for model derivation. Hospital-specific estimates of discrimination (c-statistic) and calibration (calibration intercepts and slopes) were pooled using random-effects meta-analysis methods. I2 statistics and prediction interval width quantified geographic transportability. Temporal transportability was assessed using patients from the earlier period for model derivation and patients from the later period for model validation. RESULTS: Estimates of reproducibility, pooled hospital-specific performance, and temporal transportability were on average very similar, with c-statistics of 0.75. Between hospital variation was moderate according to I2 statistics and prediction intervals for c-statistics. CONCLUSION: This study illustrates how performance of prediction models can be assessed in settings with multicenter data at different time periods. PMID- 27262238 TI - Bias was reduced in an open-label trial through the removal of subjective elements from the outcome definition. AB - OBJECTIVE: To determine whether modifying an outcome definition to remove subjective elements reduced bias in a trial that could not use blinded outcome assessment. STUDY DESIGN AND SETTING: Reanalysis of an open-label trial comparing a restrictive vs. liberal transfusion strategy for gastrointestinal bleeding. The usual definition of the primary outcome, further bleeding, allows subjective clinical symptoms to be used alone for diagnosis, whereas the definition used in the trial required more objective confirmation by endoscopy. We compared treatment effect estimates for these two definitions. RESULTS: Fewer subjective symptom-identified events were confirmed using more objective methods in the restrictive arm (18%) than in the liberal arm (56%), indicating differential assessment between arms. An analysis using all events (both subjective and more objective) led to an odds ratio of 0.83 (95% confidence interval [CI]: 0.50 1.37). When only events confirmed using more objective methods were included, the odds ratio was 0.50 (95% CI: 0.32-0.78). The ratio of the odds ratios was 1.66, indicating that including unconfirmed events in the definition biased the treatment effect upward by 66%. CONCLUSION: Modifying the outcome definition to exclude subjective elements substantially reduced bias. This may be a useful strategy for reducing bias in trials that cannot blind outcome assessment. PMID- 27262240 TI - Sparse asynchronous cortical generators can produce measurable scalp EEG signals. AB - We investigate to what degree the synchronous activation of a smooth patch of cortex is necessary for observing EEG scalp activity. We perform extensive simulations to compare the activity generated on the scalp by different models of cortical activation, based on intracranial EEG findings reported in the literature. The spatial activation is modeled as a cortical patch of constant activation or as random sets of small generators (0.1 to 3cm(2) each) concentrated in a cortical region. Temporal activation models for the generation of oscillatory activity are either equal phase or random phase across the cortical patches. The results show that smooth or random spatial activation profiles produce scalp electric potential distributions with the same shape. Also, in the generation of oscillatory activity, multiple cortical generators with random phase produce scalp activity attenuated on average only 2 to 4 times compared to generators with equal phase. Sparse asynchronous cortical generators can produce measurable scalp EEG. This is a possible explanation for seemingly paradoxical observations of simultaneous disorganized intracranial activity and scalp EEG signals. Thus, the standard interpretation of scalp EEG might constitute an oversimplification of the underlying brain activity. PMID- 27262239 TI - How reliable are MEG resting-state connectivity metrics? AB - MEG offers dynamic and spectral resolution for resting-state connectivity which is unavailable in fMRI. However, there are a wide range of available network estimation methods for MEG, and little in the way of existing guidance on which ones to employ. In this technical note, we investigate the extent to which many popular measures of stationary connectivity are suitable for use in resting-state MEG, localising magnetic sources with a scalar beamformer. We use as empirical criteria that network measures for individual subjects should be repeatable, and that group-level connectivity estimation shows good reproducibility. Using publically-available data from the Human Connectome Project, we test the reliability of 12 network estimation techniques against these criteria. We find that the impact of magnetic field spread or spatial leakage artefact is profound, creates a major confound for many connectivity measures, and can artificially inflate measures of consistency. Among those robust to this effect, we find poor test-retest reliability in phase- or coherence-based metrics such as the phase lag index or the imaginary part of coherency. The most consistent methods for stationary connectivity estimation over all of our tests are simple amplitude envelope correlation and partial correlation measures. PMID- 27262241 TI - Domain adaptation for Alzheimer's disease diagnostics. AB - With the increasing prevalence of Alzheimer's disease, research focuses on the early computer-aided diagnosis of dementia with the goal to understand the disease process, determine risk and preserving factors, and explore preventive therapies. By now, large amounts of data from multi-site studies have been made available for developing, training, and evaluating automated classifiers. Yet, their translation to the clinic remains challenging, in part due to their limited generalizability across different datasets. In this work, we describe a compact classification approach that mitigates overfitting by regularizing the multinomial regression with the mixed l1/l2 norm. We combine volume, thickness, and anatomical shape features from MRI scans to characterize neuroanatomy for the three-class classification of Alzheimer's disease, mild cognitive impairment and healthy controls. We demonstrate high classification accuracy via independent evaluation within the scope of the CADDementia challenge. We, furthermore, demonstrate that variations between source and target datasets can substantially influence classification accuracy. The main contribution of this work addresses this problem by proposing an approach for supervised domain adaptation based on instance weighting. Integration of this method into our classifier allows us to assess different strategies for domain adaptation. Our results demonstrate (i) that training on only the target training set yields better results than the naive combination (union) of source and target training sets, and (ii) that domain adaptation with instance weighting yields the best classification results, especially if only a small training component of the target dataset is available. These insights imply that successful deployment of systems for computer-aided diagnostics to the clinic depends not only on accurate classifiers that avoid overfitting, but also on a dedicated domain adaptation strategy. PMID- 27262242 TI - The neurophysiological basis of reward effects on backward inhibition processes. AB - The ability to flexibly switch between tasks is an important faculty in daily life. One process that has been suggested to be an important aspect of flexible task switching is the inhibition of a recently performed task. This is called backward inhibition. Several studies suggest that task switching performance can be enhanced by rewards. However, it is less clear in how far backward inhibition mechanisms are also affected by rewards, especially when it comes to the neuronal mechanisms underlying reward-related modulations of backward inhibition. We therefore investigated this using a system neurophysiological approach combining EEG recordings with source localization techniques. We demonstrate that rewards reduce the strength of backward inhibition processes. The neurophysiological data shows that these reward-related effects emerge from response and/or conflict monitoring processes within medial frontal cortical structures. Upstream processes of perceptual gating and attentional selection, as well as downstream processes of context updating and stimulus-response mapping are not modulated by reward, even though they also play a role in backward inhibition effects. PMID- 27262243 TI - Screening for parasitic infections: One doctor's experience. PMID- 27262244 TI - Forget EHRs--Let us get back to the practice of medicine. PMID- 27262245 TI - An unconscious bias in this EHR study? PMID- 27262246 TI - Tips and algorithms to get your patient's BP to goal. AB - Having diagnosed, treated, and studied hypertension for more than 3 decades, this author offers advice and 3 handy algorithms to help you optimize your care. PMID- 27262247 TI - Non-alcoholic fatty liver disease: What's in our arsenal? AB - Lifestyle changes and metabolic syndrome management are the best interventions for NAFLD. Less clear is which agents to use for liver-directed pharmacotherapy. PMID- 27262248 TI - Anxiety and depression: Easing the burden in COPD patients. AB - Anxiety and depression are common comorbidities of COPD. The simple evaluation tools and therapy options described here can help improve patients' quality of life. PMID- 27262249 TI - Uninjured athlete with edematous arm . Dx? AB - A 16-year-old boy presented to the emergency room (ER) with pain, redness, and swelling of his right upper arm that had been bothering him for 2 days. PMID- 27262250 TI - PURLs: Resistant hypertension? Time to consider this fourth-line drug. AB - For most adults with resistant hypertension, spironolactone is superior to doxazosin and bisoprolol as an adjunct to triple therapy. PMID- 27262251 TI - Patient with intractable nausea and vomiting. AB - A chest x-ray--followed by further questioning about the patient's medical history--revealed the cause of this woman's symptoms. PMID- 27262252 TI - Help Desk Answers: Are IV fluids better than oral rehydration for children with acute diarrhea and vomiting? AB - Intravenous fluid therapy (IVF) has a slightly lower failure rate than oral replacement therapy (ORT) in children with acute gastroenteritis, but the clinical significance is questionable. IVF takes longer to initiate than ORT and lengthens the hospital stay. PMID- 27262254 TI - Help Desk Answers: Surgery vs conservative management for AC joint repair: How do the 2 compare? AB - When not considering the grade of acromioclavicular (AC) joint dislocation, both conservative and surgical management lead to positive outcomes, although surgically managed patients require more time out of work. PMID- 27262253 TI - Why the AMA is (now) worth joining. AB - The AMA is partnering with several public health-oriented organizations, including the Centers for Disease Control and Prevention, to reach out to individuals with diabetes, cardiovascular disease, and cardiac risk factors to promote primary and secondary prevention strategies at a population level. PMID- 27262255 TI - An unconventional approach to chest wall pain. AB - Would acupuncture provide some relief while this patient waited for an x-ray to identify the source of his left lateral chest wall pain? PMID- 27262256 TI - Pathophysiology of Type 2 Diabetes: The Evolution of Our Understanding. AB - This review article explores scientists' current understanding of type 2 diabetes as a complex disorder that involves not just the pancreas and insulin system but also the liver, kidneys, gut, muscle, fat cells, and even the brain. An appreciation of the complex pathophysiology of type 2 diabetes allows the primary care practitioner to best manage patients with this common and serious disorder. PMID- 27262257 TI - Zinc and diabetes. AB - Zn2+ ions are essential for the normal processing and storage of insulin and altered pancreatic insulin content is associated with all forms of diabetes mellitus. Work of the past decade has identified variants in the human SLC30A8 gene, encoding the zinc transporter ZnT8 which is expressed highly selectively on the secretory granule of pancreatic islet beta and alpha cells, as affecting the risk of Type 2 Diabetes. Here, we review the regulation and roles of Zn2+ ions in islet cells, the mechanisms through which SLC30A8 variants might affect glucose homeostasis and diabetes risk, and the novel technologies including recombinant targeted zinc probes and knockout mice which have been developed to explore these questions. PMID- 27262258 TI - Stimulus responsive nanogel with innate near IR fluorescent capability for drug delivery and bioimaging. AB - A brighter, non toxic and biocompatible optical imaging agent is one of the major quests of biomedical research. Here in, we report a photoluminescent comacromer [PEG-poly(propylene fumarate)-citric acid-glycine] and novel stimulus (pH) responsive nanogel endowed with excitation wavelength dependent fluorescence (EDF) for combined drug delivery and bioimaging applications. The comacromer when excited at different wavelengths in visible region from 400nm to 640nm exhibits fluorescent emissions from 510nm to 718nm in aqueous condition. It has high Stokes shift (120nm), fluorescent lifetime (7 nanoseconds) and quantum yield (50%). The nanogel, C-PLM-NG, prepared with this photoluminescent comacromer and N,N-dimethyl amino ethylmethacrylate (DMEMA) has spherical morphology with particle size around 100nm and 180nm at pH 7.4 (physiological) and 5.5 (intracellular acidic condition of cancer cells) respectively. The studies on fluorescence characteristics of C-PLM NG in aqueous condition reveal large red shift with emissions from 523nm to 700nm for excitations from 460nm to 600nm ascertaining the EDF characteristics. Imaging the near IR emission with excitation at 535nm was accomplished using cut-off filters. The nanogel undergoes pH responsive swelling and releases around 50% doxorubicin (DOX) at pH 5.5 in comparison with 15% observed at pH 7.4. The studies on in vitro cytotoxicity with MTT assay and hemolysis revealed that the present nanogel is non-toxic. The DOX loaded C-PLM-NG encapsulated in Hela cells induces lysis of cancer cells. The inherent EDF characteristics associated with C-PLM NG enable cellular imaging of Hela cells. The studies on biodistribution and clearance mechanism of C-PLM-NG from the body of mice reveal bioimaging capability and safety of the present nanogel. This is the first report on a polymeric nanogel with innate near IR emissions for bioimaging applications. PMID- 27262259 TI - Surface functionalization with strontium-containing nanocomposite coatings via EPD. AB - Metal orthopedic implants still face challenges in some compromised conditions, partly due to bio-inertness. The present study aimed to functionalize metallic implants with organic-inorganic nanocomposite (strontium-containing chitosan/gelatin) coatings through a simple single-step electrophoretic deposition under mild conditions. The surface characterization and in vitro cellular response were studied and compared with chitosan/gelatin (CS/G) coatings. SEM images suggested the inorganic nanoparticles may be encapsulated within or mixed with organic polymers. The XRD patterns showed that strontium carbonate was generated in the coatings. The TEM images revealed strontium containing nanoparticles were released from the coatings in PBS. The continuous release after the initial burst release ensured the enduring effects of the functionalized surface. The tensile bond strength of the coatings to the substrates increased after the addition of strontium. In vitro cellular study confirmed that strontium-containing coatings supported the proliferation of MC3T3 E1 cells and exhibited excellent ability to enhance the differentiation of such pre-osteoblasts. Therefore, such organic-inorganic nanocomposite coatings are a promising candidate to functionalize orthopedic implant surfaces. PMID- 27262261 TI - Likelihood of Death Within One Year Among a National Cohort of Hospital Inpatients in Scotland. PMID- 27262260 TI - Nanogels fabricated from bovine serum albumin and chitosan via self-assembly for delivery of anticancer drug. AB - In this study, bovine serum albumin (BSA) and chitosan (CS) were used to prepare BSA-CS nanogels by a simple green self-assembly technique. Then the nanogels were successfully used to entrap doxorubicin hydrochloride (DOX) with an entrapment ratio of 46.3%, aiming to realize the slow-release effect and lower the cytotoxicity of DOX. The IC50 values of DOX-loaded BSA-CS (DOX-BSA-CS) and free DOX obtained by MTT assay in SGC7901 cells were 0.22 and 0.05MUg/mL, respectively. The cytotoxicity of DOX significantly decreased within 24h after encapsulation by the nanogels, indicating that the loaded drug could slowly release within 24h and the BSA-CS was a good slow release system. The cellular uptake experiments indicated DOX-BSA-CS diffused faster into the cancer cell than the bare drug. The flow cytometry and TUNEL assay proved DOX-BSA-CS could induce a larger apoptosis proportion of gastric cancer cells 7901 than the bare drug and it is promising to be used for curing gastric cancer. PMID- 27262262 TI - Catalytic properties, localization, and in vivo role of Px IV, a novel tryparedoxin peroxidase of Trypanosoma brucei. AB - Px IV is a distant relative of the known glutathione peroxidase-type enzymes of African trypanosomes. Immunofluorescence microscopy of bloodstream cells expressing C-terminally Myc6-tagged Px IV revealed a mitochondrial localization. Recombinant Px IV possesses very low activity as glutathione peroxidase but catalyzes the trypanothione/tryparedoxin-dependent reduction of hydrogen peroxide and, even more efficiently, of arachidonic acid hydroperoxide. Neither overexpression in bloodstream cells nor the deletion of both alleles in bloodstream or procyclic parasites affected the in vitro proliferation. Trypanosoma brucei Px IV shares 58% of all residues with TcGPXII. The orthologous enzymes have in common their substrate preference for fatty acid hydroperoxides. However, the T. cruzi protein has been reported to be localized in the endoplasmic reticulum and to be specific for glutathione as reducing agent. Taken together, our data show that Px IV is a low abundant tryparedoxin peroxidase of T. brucei that is not essential, at least under culture conditions. PMID- 27262263 TI - Medicolegal consequences of thoracic gossypiboma: A case report. AB - The term gossypiboma is used to describe a retained surgical sponge after operation. It is a rare but it is associated with severe medical and legal consequences. The diagnosis can be missed despite radiological investigations. We report a case of a 15-year-old female who presented with fever, cough, dyspnea and hemoptysis. She had a history of hydatid cyst operation 2 years ago. Post discharge follow up occurred for two years on hospital where hydatid cyst surgery had been done. Radiological investigations were inconclusive in detecting the retained sponge despite radiopaque marker. So gossypiboma should be kept in mind as a differential diagnosis in postoperative cases presenting as persistent respiratory symptoms after the operation. PMID- 27262264 TI - Development and evaluation of a double antibody sandwich ELISA for the detection of human sDC-SIGN. AB - sDC-SIGN is the soluble form of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN, CD209), which is a molecule involved with pathogen recognition and immune regulation. However, there is no commercially available ELISA kit for detecting human sDC-SIGN, and the normal range of this molecule is unknown. Here, we describe an ELISA for detecting human sDC-SIGN with high specificity. First, sDC-SIGN protein was expressed and purified. Monoclonal and polyclonal antibodies were then raised against the purified protein and subsequently characterized. A sandwich ELISA was developed using polyclonal antibodies specific for sDC-SIGN for capture and a biotin labeled monoclonal antibody specific for sDC-SIGN for detection of protein. This method has sensitivity up to 0.2 ng/ml. Using this ELISA, we found that the concentration of sDC-SIGN in sera of healthy volunteers ranges from 0-319 ng/ml with a mean concentration of 27.14 ng/ml. Interestingly, the concentration of sDC SIGN in sera from patients with cancer or chronic hepatitis B virus (CHB) infection was lower than that of health controls. The mean concentrations of sDC SIGN in cancer patients and chronic hepatitis B virus infection patients were 3.2 ng/ml and 3.8 ng/ml, respectively. We developed a sandwich ELISA for detecting human sDC-SIGN and demonstrated its use by assessing sera concentrations of sDC SIGN in patients with cancer and chronic CHB infection compared to that of healthy controls. PMID- 27262265 TI - Concurrent and longitudinal effects of maternal and paternal warmth on depression symptoms in children and adolescents. AB - The main aim of this study is to examine the concurrent and longitudinal effects of perceived affection of mothers and fathers separately on the self-reported symptoms of children's depression. Data were obtained from a 3-wave study of 535 families with children (41.3% boys) aged 9-15 years of age. Structural equation models were performed to test different models. Significant effects of mothers' and fathers' affection on depression symptomatology over the three years were found. The longitudinal effects of parental warmth on the child's depression symptoms were mediated over time by the previous levels of the mother's and father's warmth. The presence of parental warmth can lessen the severity of depression symptoms, especially when paternal and maternal warmth are applied consistently over a long period of time. These results were invariant across the child's sex. Treatments for childhood depression should take place over extended periods of time including both fathers and mothers. PMID- 27262266 TI - Racial-ethnic related clinical and neurocognitive differences in adults with gambling disorder. AB - Recent epidemiological data suggest that the lifetime prevalence of gambling problems differs depending on race-ethnicity. Understanding variations in disease presentation in blacks and whites, and relationships with biological and sociocultural factors, may have implications for selecting appropriate prevention strategies. 62 non-treatment seeking volunteers (18-29 years, n=18 [29.0%] female) with gambling disorder were recruited from the general community. Black (n=36) and White (n=26) participants were compared on demographic, clinical and cognitive measures. Young black adults with gambling disorder reported more symptoms of gambling disorder and greater scores on a measure of compulsivity. In addition they exhibited significantly higher total errors on a set-shifting task, less risk adjustment on a gambling task, greater delay aversion on a gambling task, and more total errors on a working memory task. These findings suggest that the clinical and neurocognitive presentation of gambling disorder different between racial-ethnic groups. PMID- 27262267 TI - Individual and environmental contingencies associated with multiple suicide attempts among U.S. military personnel. AB - Suicidal behavior among U.S. military personnel persists as a significant public health issue. Previous research indicates the primary motive for suicide attempts among military personnel is the desire to reduce or alleviate emotional distress, a finding that converges with studies in nonmilitary samples. Much less is understood about the consequences of a first suicide attempt that could influence the occurrence of additional suicide attempts. In order to identify these contingencies, 134 active duty Soldiers who had attempted suicide (n=69 first time attempters, n=65 multiple attempters) participated in structured interviews focused on their experiences immediately following their first attempt. Soldiers were more likely to have made multiple suicide attempts if they were younger at the time of their first attempt, were not admitted to a hospital or treatment program after their first attempt, or experienced emotional and psychological relief immediately afterwards. Results suggest that Soldiers who experience emotional and/or psychological relief immediately after their first suicide attempt or do not receive treatment are more likely to make additional suicide attempts. PMID- 27262268 TI - Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release. AB - The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What' more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system and pharmaceutic adjuvant. PMID- 27262269 TI - From single excipients to dual excipient platforms in dry powder inhaler products. AB - Recent years have seen a marked diversification of excipient based formulation strategies used for the development and commercialisation of dry powder inhaler (DPI) products. These innovative approaches not only provide benefits to patients and health care professionals through the availability of a wider range of therapeutic DPI products, but, importantly, also allow formulators to exploit the potential opportunities that excipients provide for the development of DPIs. Whilst many DPI products have, and continue to be developed using a single formulation excipient, the commercialisation of DPI products which contain the two excipients lactose monohydrate and magnesium stearate, namely the 'dual excipient platform' has recently been achieved. This article provides an overview of the background and current status of the development of such 'dual excipient platform' based DPI products. PMID- 27262270 TI - Solvent database and in silico classification: A new methodology for solvent substitution and its application for microencapsulation process. PMID- 27262271 TI - Application of X-ray microtomography for the characterisation of hollow polymer stabilised spray dried amorphous dispersion particles. AB - The aim of this study was to investigate the capability of X-ray microtomography to obtain information relating to powder characteristics such as wall thickness and solid volume fraction for hollow, polymer-stabilised spray dried dispersion (SDD) particles. SDDs of varying particle properties, with respect to shell wall thickness and degree of particle collapse, were utilised to assess the capability of the approach. The results demonstrate that the approach can provide insight into the morphological characteristics of these hollow particles, and thereby a means to understand/predict the processability and performance characteristics of the bulk material. Quantitative assessments of particle wall thickness, particle/void volume and thereby solid volume fraction were also demonstrated to be achievable. The analysis was also shown to be able to qualitatively assess the impact of the drying rate on the morphological nature of the particle surfaces, thus providing further insight into the final particle shape. The approach demonstrated a practical means to access potentially important particle characteristics for SDD materials which, in addition to the standard bulk powder measurements such as particle size and bulk density, may enable a better understanding of such materials, and their impact on downstream processability and dosage form performance. PMID- 27262272 TI - Photocatalytic activity of porous multiwalled carbon nanotube-TiO2 composite layers for pollutant degradation. AB - TiO2 nanoparticles are suitable building blocks nanostructures for the synthesis of porous functional thin films. Here we report the preparation of films using brookite, P25 titania and anatase pristine nanoparticles and of nanocomposite layers combining anatase nanoparticles and multi-walled carbon nanotube (MWCNT) at various concentrations. The structure and phase composition of the layers were characterized by X-ray diffraction and Raman spectroscopy. Their morphology and texture properties were determined by scanning electron microscopy and krypton adsorption experiments, respectively. Additionally to a strong absorption in the UV range, the composites exhibited light absorption in the visible range as well. The photocatalytic performance of the layers was tested in the degradation of aqueous solutions of 4-chlorophenol serving as a model of an eco-persistent pollutant. Besides the determination of the decrease in the concentration of 4 chlorophenol, also the formation of intermediate degradation products, namely hydroquinone and benzoquinone, was followed. The presence of MWCNTs had a beneficial effect on the photocatalytic performance, a marked increase in the photocatalytic degradation rate constant being observed even at very low concentrations of MWCNTs. Compared to a P25 reference layer, the first order rate reaction constant increased by about 100% for the composite films containing MWCNTs at concentrations above 0.6 wt%. The key parameters for the enhancement of the photocatalytic performance are discussed. The presence of carbon nanotubes influences beneficially the degradation of 4-chlorophenol by an attack of the primarily photoproduced hydroxyl radicals onto the 4-chlorophenol molecules. The degradation due to the direct charge transfer is practically not influenced at all. PMID- 27262273 TI - Novel polyvinylidene fluoride nanofiltration membrane blended with functionalized halloysite nanotubes for dye and heavy metal ions removal. AB - Membrane separation is an effective method for the removal of hazardous materials from wastewater. Halloysite nanotubes (HNTs) were functionalized with 3 aminopropyltriethoxysilane (APTES), and novel polyvinylidene fluoride (PVDF) nanofiltration membranes were prepared by blending with various concentrations of APTES grafted HNTs (A-HNTs). The morphology structure of the membranes were characterized by scanning electron microscope (SEM) and atomic force microscopy (AFM). The contact angle (CA), pure water flux (PWF) and antifouling capacity of membranes were investigated in detail. In addition, the separation performance of membranes were reflected by the removal of dye and heavy metal ions in simulated wastewater. The results revealed that the hydrophilicity of A-HNTs blended PVDF membrane (A-HNTs@PVDF) was enhanced significantly. Owing to the electrostatic interaction between membrane surface and dye molecules, the dye rejection ratio of 3% A-HNTs@PVDF membrane reached 94.9%. The heavy metal ions rejection ratio and adsorption capacity of membrane were also improved with the addition of A HNTs. More importantly, A-HNTs@PVDF membrane exhibited excellent rejection stability and reuse performances after several times fouling and washing tests. It can be expected that the present work will provide insight into a new method for membrane modification in the field of wastewater treatment. PMID- 27262274 TI - Graphene/biofilm composites for enhancement of hexavalent chromium reduction and electricity production in a biocathode microbial fuel cell. AB - In this study, a simple method of biocathode fabrication in a Cr(VI)-reducing microbial fuel cell (MFC) is demonstrated. A self-assembling graphene was decorated onto the biocathode microbially, constructing a graphene/biofilm, in situ. The maximum power density of the MFC with a graphene biocathode is 5.7 times that of the MFC with a graphite felt biocathode. Cr(VI) reduction was also enhanced, resulting in 100% removal of Cr(VI) within 48h, at 40mg/L Cr(VI), compared with only 58.3% removal of Cr(VI) in the MFC with a graphite felt biocathode. Cyclic voltammogram analyses showed that the graphene biocathode had faster electron transfer kinetics than the graphite felt version. Energy dispersive spectrometer (EDS) and X-ray photoelectron spectra (XPS) analysis revealed a possible adsorption-reduction mechanism for Cr(VI) reduction via the graphene biocathode. This study attempts to improve the efficiency of the biocathode in the Cr(VI)-reducing MFC, and provides a useful candidate method for the treatment of Cr(VI) contaminated wastewater, under neutral conditions. PMID- 27262276 TI - Precipitation of organic arsenic compounds and their degradation products during struvite formation. AB - Roxarsone (ROX) and arsanilic acid (ASA) have been extensively used as organoarsenic animal feed additives. Organic arsenic compounds and their degradation products, arsenate (As(V)) and arsenite (As(III)), exist in the effluent from anaerobic reactors treating animal manure contaminated by ROX or ASA with ammonium (NH4(+)-N) and phosphate (PO4(3-)-P) together. Therefore, arsenic species in the effluent might be involved in the struvite formation process. In this study, the involvement of organic arsenic compounds and their degradation products As(V) and As(III) in the struvite crystallization was investigated. The results demonstrated that arsenic compounds did not substantially affect the PO4(3-)-P recovery, but confirmed the precipitation of arsenic during struvite formation. The precipitation of arsenic compounds in struvite was considerably affected by a solution pH from 9.0 to 11.0. With an increase in pH, the content of ASA and ROX in the precipitation decreased, but the contents of As(III) and As(V) increased. In addition, the arsenic content of As(V) in the struvite was higher than that of As(III), ASA and ROX. The results indicated that the struvite could be contaminated when the solution contains arsenic species, but that could be minimized by controlling the solution pH and maintaining anaerobic conditions during struvite formation. PMID- 27262275 TI - Laccase-catalyzed removal of the antimicrobials chlorophene and dichlorophen from water: Reaction kinetics, pathway and toxicity evaluation. AB - As active agents in cleaning and disinfecting products, antimicrobials have been widely spread in the environment and have drawn extensive attention as potential threats to the ecological system and human health. In this study, the laccase catalyzed removal of two emerging antimicrobials, chlorophene (CP) and dichlorophen (DCP), was investigated under simulated environmental conditions. Intrinsic reaction kinetics showed that the removal of CP and DCP followed second order reaction kinetics, first-order with respect to both the enzyme and the substrate concentration. It was also found that fulvic acid could suppress the transformation of CP and DCP by reversing the oxidation reactions through its action as a scavenger of the free radical intermediates produced from reactions between laccase and the substrates. Several reaction products were identified by a quadrupole time-of-flight mass spectrometer, and detailed reaction pathways were proposed. For both CP and DCP, direct polymerization was the principal pathway, and the coupling patterns were further corroborated based on molecular modeling. The nucleophilic substitution of chlorine by the hydroxyl group was observed, and further oxidation products capable of coupling with each other were also found. Additionally, toxicity evaluation tests using Scenedesmus obliquus confirmed that the toxicity of CP and DCP was effectively eliminated during the reaction processes. PMID- 27262277 TI - Characterising legacy spent nuclear fuel pond materials using microfocus X-ray absorption spectroscopy. AB - Analysis of a radioactive, coated concrete core from the decommissioned, spent nuclear fuel cooling pond at the Hunterston-A nuclear site (UK) has provided a unique opportunity to study radionuclides within a real-world system. The core, obtained from a dividing wall and sampled at the fill level of the pond, exhibited radioactivity (dominantly (137)Cs and (90)Sr) heterogeneously distributed across both painted faces. Chemical analysis of the core was undertaken using microfocus spectroscopy at Diamond Light Source, UK. Mapping of Sr across the surface coatings using microfocus X-ray fluorescence (MUXRF) combined with X-ray absorption spectroscopy showed that Sr was bound to TiO2 particles in the paint layers, suggesting an association between TiO2 and radiostrontium. Stable Sr and Cs sorption experiments using concrete coupons were also undertaken to assess their interactions with the bulk concrete in case of a breach in the coating layers. MUXRF and scanning electron microscopy showed that Sr was immobilized by the cement phases, whilst at the elevated experimental concentrations, Cs was associated with clay minerals in the aggregates. This study provides a crucial insight into poorly understood infrastructural contamination in complex systems and is directly applicable to the UK's nuclear decommissioning efforts. PMID- 27262278 TI - Morphological and elemental properties of urban aerosols among PM events and different traffic systems. AB - Morphology and elemental composition of individual fine ambient particles varied among types of PM events and between two different urban environments having different major transportation systems (gasoline/diesel vehicles versus motorcycles). Carbonaceous particles were the most dominant in PM events, whereas S-rich particles were the highest in non-events at urban Gwangju in Korea. The aged soot, semi-volatile organic (SVO), and non-volatile organic (NVO) particles were more abundant in the polluted-long range transport (LTP) event than those in the dust-LTP event and non-event. In the dust-LTP event, the aged mineral dust particles outnumbered the fresh ones, suggesting the mineral dust particles were aged during their long-range transport. At HoChiMinh (HCM) in Vietnam, the fraction of carbonaceous particles was much higher than Gwangju (66% versus 30%) possibly due to more abundant two-stroke motor vehicles at HCM. Of the carbonaceous particles, combustion soot (19%) was the highest, followed by NVO (18%), SVO (17%), and biological particles (11%) at HCM, whereas SVO (11%) and NVO (10%) particles were the highest, followed by combustion soot particles (8%) at Gwangju. The higher fraction of mineral dust particles was also observed at HCM, indicating the sampling site was influenced by dust from unpaved roads and construction sites. PMID- 27262279 TI - Size dependent effect of ZnO nanoparticles on endoplasmic reticulum stress signaling pathway in murine liver. AB - ZnO nanoparticles (NPs) have been assessed to show adverse effects on the liver, but the molecular mechanisms and the role of nanoparticle properties in these adverse reactions have not been sufficiently studied. In this study, the toxicity of various sizes of ZnO particles (bulk, 90nm, and 30nm) that were ingested orally over a period of 3days were evaluated in mice. The blood biochemistry, hematological analyses, and histopathological evaluation showed that there was apparent toxicity caused by smaller ZnO NPs (30nm) in liver. The smallest ZnO NPs showed highest accumulation in the mice liver. The RT-qPCR data indicated that 30nm ZnO NPs can induce significant endoplasmic reticulum (ER) stress responses. The ER stress marker of PERK, eIF2alpha, ATF4, Chop, JNK, caspase-12, caspase-9, GRP94, and Bax at the mRNA levels were higher expression in 30nm ZnO NP than that in bulk or 90nm ZnO. These findings implied that the smaller ZnO NPs (30nm) activated ER stress responses that signified severe apoptosis in murine liver. PMID- 27262281 TI - Removal of pesticides from white and red wines by microfiltration. AB - The aim of this work is the investigation of microfiltration in removing pesticides from a white and a red Greek wine. Six membranes with pore size 0.45MUm were investigated. Two mixtures of 23 and 9 pesticides, and single pesticide solutions were added in the wine. The pesticides tested belong to 11 chemical groups. Solid phase extraction (SPE) followed by gas chromatography (GC) with electron capture detector (ECD) were performed to analyze pesticide residues of the filtered fortified wine. Distinct behavior was exhibited by each membrane. Cellulose acetate and cellulose nitrate showed higher mean pesticide removal for both wines, followed by polyethersulfone, regenerated cellulose, and polyamides. The filtration effectiveness was correlated to the membrane type and to the pesticide chemical structure and properties (octanol-water partition coefficient, water solubility) and compared for the wines tested. In most cases, the more hydrophobic pesticides (pyrethroids and aldrin) showed higher removal from red wine than white wine. Adsorption on membranes was increased by increasing hydrophobicity and decreasing hydrophilicity of organic pesticide molecule. The removal of each pesticide from its single solution was generally higher than that from its mixtures, allowing the estimation of the antagonistic and synergistic effects of pesticides in the mixtures. PMID- 27262280 TI - Combined use of flow cytometry and microscopy to study the interactions between the gram-negative betaproteobacterium Acidovorax facilis and uranium(VI). AB - The former uranium mine Konigstein (Saxony, Germany) is currently in the process of remediation by means of controlled underground flooding. Nevertheless, the flooding water has to be cleaned up by a conventional wastewater treatment plant. In this study, the uranium(VI) removal and tolerance mechanisms of the gram negative betaproteobacterium Acidovorax facilis were investigated by a multidisciplinary approach combining wet chemistry, flow cytometry, and microscopy. The kinetics of uranium removal and the corresponding mechanisms were investigated. The results showed a biphasic process of uranium removal characterized by a first phase where 95% of uranium was removed within the first 8h followed by a second phase that reached equilibrium after 24h. The bacterial cells displayed a total uranium removal capacity of 130mgU/g dry biomass. The removal of uranium was also temperature-dependent, indicating that metabolic activity heavily influenced bacterial interactions with uranium. TEM analyses showed biosorption on the cell surface and intracellular accumulation of uranium. Uranium tolerance tests showed that A. facilis was able to withstand concentrations up to 0.1mM. This work demonstrates that A. facilis is a suitable candidate for in situ bioremediation of flooding water in Konigstein as well as for other contaminated waste waters. PMID- 27262282 TI - Study of the leaching behaviour of ladle slags by means of leaching tests combined with geochemical modelling and mineralogical investigations. AB - In this study, the leachability of freshly produced ladle slag derived from both austenitic and ferritic stainless steel production, and from electrical and structural steel production, was investigated, in order to determine whether variations in the chemical and mineralogical composition of these slags affect their leaching behaviour. The effect of the method used for slag cooling was also studied. The results obtained by using the single batch test were combined with those obtained by means of more sophisticated characterisation leaching tests, which, in combination with geochemical speciation modelling, helped to better identify the release mechanisms and phases that control the release of individual elements. It was found that, although variations in the chemical composition of the slag can affect the slag's minerology, neither such variations, nor the choice of the slag cooling treatment, have a significant effect on the leachability of individual elements, since the leaching is governed by surface phenomena. In fact, the mineral transformations on the slag surface, rather than the bulk mineral composition, dictate the release of these elements from the ladle slag. The solubility-controlling phases were predicted by multi-element modelling, and verified to the extent made possible by the performed mineralogical investigations. PMID- 27262283 TI - Frequency and risk factors of functional gastro-intestinal disorders in a rural Indian population. AB - BACKGROUND AND AIM: As best estimates on functional gastrointestinal disorders (FGIDs) prevalence are expected from community studies, which are scanty from Asia, we evaluated the prevalence and risk factors of FGIDs in a rural Indian community. METHODS: House-to-house survey was undertaken by trained interviewers using translated-validated Rome III and hospital anxiety and depression questionnaires. RESULT: Among 3426 subjects >= 18 years old from 3 villages in Uttar Pradesh, 84% participated, of whom 80% were finally analyzed. Of these 2774 subjects (age 38.4 +/- 16.5 years, 1573 [56.7%] male), 2654 [95.7%] were vegetarian and 120 [4.3%] non-vegetarian. Socioeconomic classes were upper (16.7%), upper middle (15.1%), lower middle (22%), upper lower (22.2%), and lower (24%) using Prasad's Classification; 603 (21.7%) had FGIDs (413 [14.9%] dyspepsia, 75 [2.7%] irritable bowel syndrome (IBS) and 115 [4.1%] dyspepsia-IBS overlap), by Rome III criteria. In subjects with dyspepsia, 49/528 (9%) had epigastric pain, 141 (27%) postprandial distress syndromes (EPS, PDS) and 338 (64%) EPS-PDS overlap. IBS was more often diarrhea than constipation-predominant subtype. On univariate analysis, chewing tobacco, aerated drink, tea/coffee, disturbed sleep, vegetarianism, and anxiety parameters and presence of dyspepsia predicting occurrence of IBS were associated with FGIDs. On multivariate analysis, chewing tobacco, aerated soft drink, tea/coffee, vegetarianism, anxiety parameters, and presence of dyspepsia predicting IBS were significant. CONCLUSION: Functional gastrointestinal disorders, particularly dyspepsia-IBS overlap, are common in rural Indian population; the risk factors included chewing tobacco, aerated soft drink, tea/coffee, vegetarian diet, disturbed sleep, anxiety, and dyspepsia predicting occurrence of IBS. PMID- 27262284 TI - The rate of training response to aerobic exercise affects brain function of rats. AB - There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p < 0.05). On the reverse Morris Maze test HRT-trained rats outperformed HRT control ones. Significant difference was noted between LRT and HRT groups in redox milieu as assessed by levels of reactive oxygen species (ROS), carbonylation of proteins, nNOS and S-nitroso cysteine. Moreover the silent information regulator 1 (SIRT1), brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats. PMID- 27262285 TI - Sparteine as an anticonvulsant drug: Evidence and possible mechanism of action. AB - Sparteine is a quinolizidine alkaloid extracted from Lupinus that has numerous pharmacological properties both in humans and animal models. In the central nervous system, sparteine reduces locomotor activity, has light analgesic effects, also has no effects on short-term memory or spatial learning and does not induce changes in behavior or electroencephalographic (EEG) activity. However, the anticonvulsant profile of sparteine is not fully characterized in experimental animals and there are no data in humans. Therefore, the present review focuses on the experimental evidence supporting the anticonvulsant action of sparteine in models of acute seizures and status epilepticus (SE), as well as its possible mechanisms of action. The evidence that supports the anticonvulsant effect of (-)-Sparteine sulfate includes the inhibition of seizures induced by maximal electro-stimulation, a delay in the onset of convulsive behavior and the prolongation of survival time in mice treated with pentylenetetrazole (PTZ). Additionally, sparteine delays the onset of convulsive behavior and decreases the severity and mortality of rats treated with PTZ and pilocarpine. Sparteine decreases amplitude and frequency or blocks the epileptiform activity induced by PTZ, pilocarpine and kainic acid. Sparteine may decrease hyperexcitability through the activation of the M2 and M4 subtypes of mAChRs, which is a probable mechanism of action that together with its systemic effects may favor its anticonvulsant effects against seizures and SE. PMID- 27262286 TI - Rumpel-Leede phenomenon in a hypertensive patient due to mechanical trauma: a case report. AB - BACKGROUND: In this report, we present an interesting case of a patient with Rumpel-Leede phenomenon, a rare occurrence that can result in significant delays in medical treatment. This phenomenon is characterized by the presence of a petechial rash that results from acute dermal capillary rupture. In our patient, it occurred secondary to raised pressure in the dermal vessels caused by repeated inflation of a sphygmomanometer cuff. Contributory factors in Rumpel-Leede phenomenon include prevalent conditions such as diabetes mellitus, hypertension, thrombocytopenia, chronic steroid use, antiplatelets, and anticoagulants. CASE PRESENTATION: A 58-year-old Russian woman with diabetes and hypertension presented to our hospital with a non-ST elevation myocardial infarction, and she subsequently developed a petechial rash on her distal upper limbs. A vasculitic screen was performed, with normal results. CONCLUSIONS: Given the timing and distribution of the rash, it was felt that this was an example of Rumpel-Leede phenomenon in a susceptible individual. This is an important diagnosis to be aware of in patients with vascular risk factors presenting for acute medical care who subsequently develop a petechial rash. PMID- 27262287 TI - The comparison of adductor canal block with femoral nerve block following total knee arthroplasty: a systematic review with meta-analysis. AB - PURPOSE: Although several studies have compared the clinical efficacy of an adductor canal block (ACB) to that of a femoral nerve block (FNB) for analgesia after total knee arthroplasty (TKA), disputes mainly exist in the recovery of quadriceps strength and mobilization ability between the two methods. The aim of the present study was to compare, in a systematic review and meta-analysis, the clinical efficacy of ACB with that of FNB. METHODS: We systematically searched randomized controlled trials comparing FNB with ACB for analgesia after TKA in Pubmed and the Cochrane Library from inception to April 30th 2015. There was no limitation of publication language. Trial quality was assessed using the modified Jadad scale, and eligible data were pooled for meta-analysis. RESULTS: Five studies of 348 patients were included. Outcomes showed that patients who received ACB had similar or better recovery of quadriceps strength and mobilization ability than those that underwent FNB. Similar efficacy was found between the two strategies regarding adductor strength, pain scores [at rest (p = 0.86), at or after knee flexion (p = 0.31)], opioid consumption (p = 0.99), opioid-associated adverse effects (p = 0.60), length of hospital stay (p = 0.42), patient satisfaction (p = 0.57), and success rate of blockade (p = 0.20). CONCLUSIONS: The present study suggests that TKA patients who receive ACB can achieve similar or even better recovery of quadriceps strength and mobilization ability than those treated with FNB. Taken as a whole, ACB may be a better analgesia strategy after TKA at present. PMID- 27262288 TI - Switching therapy from intravenous beta blocker to bisoprolol transdermal patch for atrial fibrillation tachycardia. AB - Beta-blockers are important for severe-status patients with atrial fibrillation related tachycardia. Beta 1-selective intravenous injection are routinely used, but long-term administration is difficult due to cost-performance- or management related issues. A bisoprolol patch, a beta-blocker to be percutaneously absorbed, recently became commercially available in Japan. As it may facilitate effective absorption and a mild elevation of the blood concentration, we retrospectively analyzed 16 patients with atrial fibrillation-related tachycardia who were admitted to the Intensive Care Unit of Hitachi General Hospital Emergency and Critical Care Center, and underwent switching therapy from landiolol to a bisoprolol patch. For switching, the bisoprolol patch (4 mg) was attached to each patient. The bisoprolol patch was introduced 88 h after the start of landiolol administration, when the rate was approximately 3 MUg/kg/min. Landiolol injection was combined with bisoprolol for 15.4 +/- 17.5 h. Switching therapy was successful in all subjects. The introduction of the bisoprolol patch did not induce any significant changes in the blood pressure or heart rate. After the completion of landiolol administration, there were also no significant changes in either parameter. There were no adverse events. In severe-status patients, switching therapy from landiolol injection to the bisoprolol patch can be conducted safely, and might be useful for heart-rate control. PMID- 27262289 TI - A new turtle confirms the presence of Bothremydidae (Pleurodira) in the Cenozoic of Europe and expands the biostratigraphic range of Foxemydina. AB - Pleurodira is a clade of Gondwanan turtles that reached Europe at the beginning of the Late Cretaceous. It is recognized as the most abundant and diverse group of freshwater turtles in the uppermost Cretaceous record of this continent, being represented by several members of Bothremydidae. Two well-preserved and relatively complete skulls are studied in this paper. They come from lower Eocene levels of the French locality of Saint-Papoul (Aude). These specimens are recognized as attributable to a new taxon, Tartaruscola teodorii gen. et sp. nov., identified as a bothremydid. This new form constitutes the only known unambiguous and valid representative of Bothremydidae in the Cenozoic of Europe. The new taxon is diagnosed by several autapomorphies and also by an exclusive combination of characters. It is one of the few members of Bothremydini identified in the Cenozoic record and the only one described for the Eocene outside of the Ouled Abdoun Basin of Morocco. Tartaruscola teodorii is identified as a member of Foxemydina, a clade recognized here as exclusive of the European record, and whose presence in post-Mesozoic levels is demonstrated in this paper. The European Foxemydina T. teodorii and the African Bothremydina Bothremys kellyi, both from the Ypresian, are the youngest members of Bothremydini hitherto known. PMID- 27262290 TI - Multiple paternity in a viviparous toad with internal fertilisation. AB - Anurans are renowned for a high diversity of reproductive modes, but less than 1 % of species exhibit internal fertilisation followed by viviparity. In the live bearing West African Nimba toad (Nimbaphrynoides occidentalis), females produce yolk-poor eggs and internally nourish their young after fertilisation. Birth of fully developed juveniles takes place after 9 months. In the present study, we used genetic markers (eight microsatellite loci) to assign the paternity of litters of 12 females comprising on average 9.7 juveniles. In 9 out of 12 families (75 %), a single sire was sufficient; in three families (25 %), more than one sire was necessary to explain the observed genotypes in each family. These findings are backed up with field observations of male resource defence (underground cavities in which mating takes place) as well as coercive mating attempts, suggesting that the observed moderate level of multiple paternity in a species without distinct sperm storage organs is governed by a balance of female mate choice and male reproductive strategies. PMID- 27262291 TI - A structural colour ornament correlates positively with parasite load and body condition in an insular lizard species. AB - Pigment-based ornaments in vertebrates may reflect the body condition or health status of the individual in correlation with environmental stress and hormonal balance. Among the environmental factors shaping sexual colouration, parasitic infections have been stressed as an important evolutionary pressure constraining the maintenance of pigment-based ornaments. However, the honesty of structure based ornaments in vertebrates is still under debate. Structural UV-biased ornaments in Gallotia lizards were described as a trait used by conspecifics during mate and rival assessment suggesting the reliability of these signals. We investigated the relationship between parasitaemia, body condition and a structural-based ornament present in the cheek of the sexually dichromatic Canarian lacertid Gallotia galloti in a population with an almost 100 % prevalence of haemoparasites. Using spectrophotometric techniques, we found that males with higher values of cheek UV chroma were infected with more haemoparasites. No significant relationship was found between haemoparasite load and body condition. However, males with higher cheek UV chroma showed significantly better body condition. In addition, we found that cheek hue was significantly related to body condition of individuals in both sexes. In males, cheek reflectivity biased towards the UV range was significantly related to better body condition. In females, those individuals with better body condition showed more whitish cheeks with less UV suggesting that cheek hue serves as an intersexual signal for sex recognition. We conclude that the positive relationship between cheek chroma and parasite load in male lizards is compatible with both differential density of melanin and iridophore arrangement in the dermis conveying an individual's ability to cope with environmental stress. PMID- 27262292 TI - Simulation-optimization model for production planning in the blood supply chain. AB - Production planning in the blood supply chain is a challenging task. Many complex factors such as uncertain supply and demand, blood group proportions, shelf life constraints and different collection and production methods have to be taken into account, and thus advanced methodologies are required for decision making. This paper presents an integrated simulation-optimization model to support both strategic and operational decisions in production planning. Discrete-event simulation is used to represent the flows through the supply chain, incorporating collection, production, storing and distribution. On the other hand, an integer linear optimization model running over a rolling planning horizon is used to support daily decisions, such as the required number of donors, collection methods and production planning. This approach is evaluated using real data from a blood center in Colombia. The results show that, using the proposed model, key indicators such as shortages, outdated units, donors required and cost are improved. PMID- 27262293 TI - Production of 4-androstene-3,17-dione and 1,4-androstadiene-3,17-dione from rice germ and wheat germ extracts by Mycobacterium sp. AB - OBJECTIVE: To study the biotransformation of phytosterol and phytosterol containing rice germ and wheat germ ethanolic extracts to produce 4-androstene 3,17-dione (AD) and 1,4-androstadiene-3,17-dione (ADD) by Mycobacterium sp. DSM 2966 using phytosterol to hydroxypropyl-beta-cyclodextrin (2:1, 1:1 and 1:2 mol/mol) and 2 % (w/v) Tween 80 as solubilizing agents. RESULTS: A maximum yield of 180 +/- 27 mg AD l(-1) and 31 +/- 11.4 mg ADD l(-1) with a total conversion of 65 % (day 12) was obtained using 1 g phytosterol l(-1) and hydroxypropyl-beta cyclodextrin (2 : 1 mol/mol) with 2 % (w/v) Tween 80 in the fermentation medium. The most appropriate conditions for rice germ extract and wheat germ extract which gave the maximum conversion of 22 and 43 % (day 14) were obtained by using 2 % (w/v) Tween 80. CONCLUSIONS: Phytosterol and wheat germ are effective sources for AD and ADD production while rice germ required further development. Hydroxypropyl-beta-cyclodextrin (2 :1 mol/mol) and/or 2 % (w/v) Tween 80 in the biotransformation process could improve AD and ADD yields, depending on substrates and biotransformation conditions. PMID- 27262294 TI - Enterococcus faecalis promotes osteoclast differentiation within an osteoblast/osteoclast co-culture system. AB - OBJECTIVE: To investigate the effects of heat-killed Enterococcus faecalis ATCC 29212 and P25RC clinical strain (derived from an obturated root canal with apical periodontitis) on osteoclast differentiation within an osteoblast/osteoclast co culture system. RESULTS: Heat-killed E. faecalis significantly increased the proportion of multinucleated osteoclastic cells (MNCs) within the co-culture system. The IL-6 level was significantly increased upon exposure to heat-killed E. faecalis. Gene expression levels of NFATc1 and cathepsin K were significantly up-regulated compared to the untreated control. EphrinB2 and EphB4 expressions at both the mRNA and protein levels were also significantly upregulated compared to the untreated control. CONCLUSIONS: Heat-killed E. faecalis can induce osteoclast differentiation within the osteoblast/osteoclast co-culture system in vitro, possibly through ephrinB2-EphB4 bidirectional signaling. PMID- 27262295 TI - Rapid and efficient degradation of bisphenol A by chloroperoxidase from Caldariomyces fumago: product analysis and ecotoxicity evaluation of the degraded solution. AB - OBJECTIVES: To degrade enzymatically bisphenol A (BPA) that causes serious environmental concerns and is difficult to be degraded by chemical or physical methods. RESULTS: BPA (150 mg l(-1)) was completely degraded by chloroperoxidase (CPO)/H2O2 within 7 min at room temperature, atmospheric pressure with the enzyme at 6 MUg CPO ml(-1). The degradation products were identified by HPLC-MS, which suggested involvement of multiple steps. Enzymatic treatment followed by existing bioremediation technologies (activated sludge) enhanced removal of COD from 9 to 54 %. Using an ecotoxicity evaluation with Chlorella pyrenoidosa, the degradation products had a lower toxicity than BPA. CONCLUSION: BPA can be degraded rapidly and efficiently under mild conditions with chloroperoxidase at 6 MUg ml(-1). The degradation products had a lower toxicity than BPA. PMID- 27262296 TI - Establishing an efficient gene-targeting system in an itaconic-acid producing Aspergillus terreus strain. AB - OBJECTIVES: To develop an efficient gene-targeting platform in an excellent itaconic acid producing strain Aspergillus terreus CICC40205. RESULTS: The frequency of homologous recombination was improved by deleting the ku80 gene. A nutritional transformation system based on the bidirectionally selectable marker, pyrG An , was established in the ku80-/pyrG-double mutant which is convenient for following marker rescue. The modified Cre/loxP recombination system was applied for the excision of the pyrG An marker by directly introducing Cre recombinase into the protoplasts. CONCLUSIONS: This gene-targeting system is an efficient platform for sequential and multiple genetic modifications in A. terreus and is conducive to study biosynthesis mechanisms and to improve the production ability of itaconic acid and other products. PMID- 27262298 TI - A novel alpha-glucosidase inhibitory constituent from Uncaria gambir. AB - Bioactivity-guided fractionation of an aqueous methanolic extract of manufactured gambir product from Uncaria gambir with in vitro alpha-glucosidase inhibitory activity was performed to isolate a novel prenyl resorcinol derivative (1) together with seven known compounds, including two flavone glycosides (2, 3), three catechin analogues (4-6), and two simple phenolics (7, 8). Structures of the isolated compounds were determined by analysis of physical and spectroscopic data (NMR, UV, [alpha]D, and MS). All isolates were evaluated for in vitro alpha glucosidase inhibitory activity. Among the compounds, novel compound 1, possessing an unprecedented spirocyclopropane ring in the molecule, showed the most potent alpha-glucosidase inhibitory activity in this assay. On the other hand, compounds 4 and 7 showed less potent inhibitory effects in this same bioassay, with half-maximal inhibitory concentration values of 17.3 +/- 1.0 MUM and 27.0 +/- 0.9 MUM, respectively. PMID- 27262297 TI - Estimation of genetic parameters for longevity considering the cow's age at last calving. AB - The aim of this study was to estimate heritability and predict breeding values for longevity among cows in herds of Nellore breed, considering the trait cow's age at last calving (ALC), by means of survival analysis methodology. The records of 11,791 animals from 22 farms were used. The variable ALC has been used by a criterion that made it possible to include cows not only at their first calving but also at their ninth calving. The criterion used was the difference between the date of each cow's last calving and the date of the last calving on each farm. If this difference was greater than 36 months, the cow was considered to have failed and uncensored. If not, this cow was censored, thus indicating that future calving remained possible for this cow. The survival model used for the analyses was the proportional hazards model, and the base risk was given by a Weibull distribution. The heritability estimate obtained was equal to 0.25. It was found that the ALC variable had the capacity to respond to selection for the purpose of increasing the longevity of the cows in the herds. PMID- 27262299 TI - Antioxidative activities of 62 wild mushrooms from Nepal and the phenolic profile of some selected species. AB - Mushrooms have garnered immense popularity for their nutritional as well as medicinal values. The therapeutic potential of mushrooms in Nepal, a country well known for its biodiversity and natural medicinal resources, remains largely unstudied. Therefore, this study attempts to unveil the antioxidative properties of Nepalese wild mushrooms. Sixty-two wild mushroom samples were collected from several forests in different parts of Nepal. Ethanol and water extracts of the dried samples were tested for their antioxidative activities using total phenolic content (TPC), oxygen radical absorbance capacity (ORAC) assay, 2,2-diphenyl-1 picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and reducing power (RP) assays. Ethanol extracts of samples belonging to the order Hymenochaetales showed significantly high activity in all the assays. Inonotus clemensiae had an exceptionally high TPC of 643.2 mg gallic acid equivalent (GAE)/g extract and also exhibited the lowest EC50 values in DPPH (0.081 mg/mL), ABTS (0.409 mg/mL), and EC0.5 value in reducing power (RP; 0.031 mg/mL) assays. High-performance liquid chromatography (HPLC) analysis of the top ten samples with the highest TPC was done to identify the phenolic compounds in the extracts, followed by liquid chromatography-mass spectrometry (LC-MS) analysis for some unknown compounds. These findings highlight the very strong antioxidative activity of Nepalese mushrooms, and paves the way for further research to explore their economic potential. PMID- 27262300 TI - TRPA1 and TRPM8 Receptors May Promote Local Vasodilation that Aggravates Oxaliplatin-Induced Peripheral Neuropathy Amenable to 17beta-Estradiol Treatment. AB - Oxaliplatin is a widely used chemotherapeutic agent that induces both acute and chronic peripheral neuropathy. Based on previous research indicating that estrogen replacement may attenuate some forms of pain in ovariectomized animals, we examined the effects of 17beta-estradiol in OXAIPN. We discovered that local cold exposure induces an abnormal vascular response in both acute and chronic models of OXAIPN (oxaliplatin-induced peripheral neuropathy) that may be used as an easy and non-invasive method to predict which patients may be susceptible to the development of severe, chronic OXAIPN. Neuropathy was induced by injection of oxaliplatin on the first two days for the short-term OXAIPN group and twice a week for 3 weeks for the long-term OXAIPN group. Local cold-induced vascular responses were recorded in the presence or absence of subcutaneously injected transient receptor potential ankyrin 1 (TRPA1) antagonist HC033031 or transient receptor potential melastatin 8 (TRPM8) antagonist AMTB using laser Doppler flowmetry. Both short-term and long-term OXAIPN groups exhibited abnormal local cold-induced vascular responses, characterized by initial vasodilation followed by vasoconstriction. Local blockade of TRPA1 or TRPM8 receptors attenuated the initial vasodilation. Changes in release of calcitonin gene related peptide (CGRP) and nitric oxide (NO) metabolites due to local cold exposure at the hind paw were also involved. Administration of 17beta-estradiol resulted in an anti nociceptive effect and attenuating abnormal vasodilation. PMID- 27262301 TI - Pretreatment quality of life, performance status and their relation to treatment discontinuation and treatment changes in high-risk breast cancer patients receiving chemotherapy: results from the prospective randomized ADEBAR trial. AB - BACKGROUND: Health-related quality of life (QoL) is a self-assessed construct indicating how people feel in regard to aspects of their health. Performance status (PS) is evaluated by the treating physician. We examined whether pretreatment QoL and PS are related to subsequent treatment discontinuation and treatment changes in high-risk breast cancer patients receiving chemotherapy. METHODS: We conducted a prospective cohort study with data from a randomized phase III trial comparing FEC- and EC-DOC-chemotherapy in patients with primary breast cancer (ADEBAR). We examined the patient's request to discontinue the study, discontinuation due to toxicity, the prolongation of therapy, and dose reduction. Baseline QoL was assessed using the EORTC QLQ-C30. PS was evaluated using the Eastern Cooperative Oncology Group Scale (ECOG). Four QoL scales were selected prior to analysis as outcomes: global health, physical functioning, emotional functioning, and fatigue. Multivariate binary logistic regression analyses were used to test for differences within the independent variables. MAIN RESULTS: 1322 patients were included. 1094 (82.8 %) patients completed therapy according to protocol. 6.3 % stopped therapy due to toxicity and 4.4 % refused treatment. Global health was not related to any of the four QoL outcomes. Physical functioning had the strongest impact on QoL, when comparing the fittest group to the lowest quintile [OR 2.14 (95 % CI 1.00-4.60)]. ECOG 0 compared to worse than 1 was strongly correlated to therapy discontinuation due to toxicity [OR 20.15 (95 % CI 9.48-42.83)] and treatment refusal [OR 8.32 (95 % CI 3.81 18.14)]. CONCLUSIONS: Pretreatment QoL, especially physical functioning, is associated with subsequent therapy discontinuation due to toxicity and with changes of the treatment protocol. Pretreatment performance status is strongly associated with therapy discontinuation due to toxicity and with treatment refusal. PMID- 27262303 TI - Why have a special issue on methods used in clinical pharmacy practice research? PMID- 27262302 TI - Influence of ACE gene on differential response to sertraline versus fluoxetine in patients with major depression: a randomized controlled trial. AB - BACKGROUND: Extensive distribution of the different components of renin angiotensin system (RAS) in the brain, along with their roles in promoting anxiety, depression and brain inflammation, opposes RAS as a potential therapeutic target in major depression. Actions of angiotensin II, the main product of RAS, are reduced by antidepressants and this signifies the complex interplay of different mechanisms involved in response to therapy. Here, we hypothesized that genetic polymorphisms of RAS may affect the outcome of therapy in depressed patients. METHODS: The frequencies of variants of genes encoding for angiotensin-converting enzyme (ACE) insertion/deletion (I/D), rs4291 and rs4343 polymorphisms were determined in extracted DNAs of 200 newly diagnosed depressed patients. Patients were randomly divided into two groups, one treated with fluoxetine and the other treated with sertraline for 12 weeks. Responsive patients were determined by psychiatrist using Hamilton questionnaire and were compared with regard to their genetic variants. RESULTS: Carriers of the D allele and patients with DD genotype responded significantly better to sertraline than to fluoxetine (P = 0.0006, odds ratio (OR) = 3.0, 95 % confidence interval (CI) = 1.80-5.08; P = 0.006, OR = 3.7, 95 % CI = 1.66-8.29, respectively). Mutant genotypes (GG and TT) of rs4343 and rs4291 polymorphisms were also more frequent in patients responding to sertraline, though not achieving the significance level (P = 0.162 and P = 0.256, respectively). CONCLUSION: These findings suggest that special genetic variants of RAS may influence or be an indicator for better response to sertraline. PMID- 27262305 TI - Induced Folding Under Membrane Mimetic and Acidic Conditions Implies Undiscovered Biological Roles of Prokaryotic Ubiquitin-Like Protein Pup. AB - Ubiquitin-like proteins play important roles in diverse biological processes. In Mycobacterium tuberculosis, Pup (prokaryotic ubiquitin-like protein), a functional homologue of eukaryotic ubiquitin, interacts with the proteasome ATPase subunit Mpa to recognize and unfold substrates, and then translocate them into the proteasome core for degradation. Previous studies revealed that, Pup, an intrinsically disordered protein (IDP), adopts a helical structure upon binding to the N-terminal coiled-coil domain of Mpa, at its disordered C-terminal region. In the present study, using circular dichroism (CD), surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR), we show that membrane mimetic and acidic conditions also induce Pup to adopt helical conformations. Moreover, at low pH, Pup, via both of its N- and C-terminal regions, binds to Mpa on sites from the N-terminal region in addition to the C-terminal region of the coiled coil domain. Our results imply Pup may play undiscovered roles in some biological processes e.g. those involve in membrane. PMID- 27262306 TI - The Amazing World of Peptide Engineering: the Example of Antimicrobial Peptides from Frogs and Their Analogues. AB - This review discusses the importance and properties of antimicrobial peptides from frogs and their synthetic analogues as potential therapeutic alternatives in fighting not only bacterial infections, but also protozoans involved with the major neglected diseases, which afflict human populations (e.g., Chagas disease, African sleeping sickness, Leishmaniasis and malaria). Here, we emphasize their multifunctional properties such as promising broad-spectrum drugs that target protozoan parasites too. PMID- 27262307 TI - High-Level Secretory Expression and Purification of Recombinant Human Interleukin 1 Beta in Pichia pastoris. AB - As an important pro-inflammatory cytokine, interleukin-1beta (IL-1beta) participates in a variety of physiological and pathological responses. In order to obtain higher yielded recombinant human interleukin-1 beta (rhIL-1beta), we cloned hIL-1beta cDNA sequences based on the coding sequence of human mature IL 1beta. After recombinant pPICZalphaA/hIL-1beta was separated and sequenced, we transformed recombinant pPICZalphaA/hIL-1beta into Pichia pastoris GS115, SMD1168 and X-33 strain via electroporation. The results showed that recombinant pPICZalphaA/ hIL-1beta had the highest expression level in X-33 Pichia pastoris. Subsequently, rhIL-1beta was purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and identified by Western blot. Then the fermentation process was optimized to increase product yield. Under the fermentation conditions of the absorption value of fermentation liquor before induction of 600, oxygen concentration of 20%, methanol concentration of 0.25% with pH 5.0, the yield of rhIL-1beta reached to 250 mg/L after 72 h induction at 26 degrees C. After aqueous two-phase extraction combined with chromatography, the purity of rhIL-1beta was 95% and the yield was up to 85%. The biological activity of rhIL-1beta was detected by MTT assay, and the result showed that rhIL 1beta significantly inhibited the growth and proliferation of B16 melanoma cells. PMID- 27262308 TI - An extremely rare case report of surgery of lung cancer with the absence of azygos vein. AB - In thoracic surgery, we occasionally encounter vessel anomalies. We herein report an extremely rare surgical case with the absence of the azygos vein. Mediastinal vascular abnormalities are said to be rare. The etiology of vascular abnormalities of the whole body, including the chest is known gene mutations, hormone abnormalities, infection, and trauma. But, many causes have been unknown. In thoracic surgery field, there is some reports and literature about pulmonary arteriovenous malformation, pulmonary sequestration, and partial anomalous pulmonary venous return. But reports about absence of azygos vein are not much. It is considered that it is less likely to become a problem in clinical. As we discussed in the paper, it will be more interesting if the association with PLSVC reveals from more cases. A 58-year-old man was admitted to our hospital in order to undergo operation for the treatment of lung cancer. We detected absence of the azygos vein by preoperative computed tomography (CT). Furthermore, three dimensional angiography (3D-angiography) showed that the right superior intercostal vein and hemiazygos vein in the left thoracic cavity were more developed than usual. Then, we discuss the key points during surgery and suggest the potential association between the absence of the azygos vein and a persistent left superior vena cava (PLSVC). PMID- 27262309 TI - Enhanced recovery after surgery (ERAS) pathway vs traditional care in laparoscopic rectal resection: a single-center experience. AB - BACKGROUND: The aim of this study was to compare the outcome of an enhanced recovery after surgery (ERAS) pathway with traditional perioperative care in laparoscopic rectal resection. METHODS: A retrospective analysis of prospectively collected data was conducted. Single-center consecutive patients who underwent laparoscopic rectal surgery after an ERAS program were compared with patients who received traditional care over an 8-year period. Primary and total length of stay, and readmission, morbidity and mortality rates were analyzed. For ERAS group, the actual adherence to protocol was also evaluated. RESULTS: Two hundred and ninety-seven patients, 162 in the ERAS group and 135 in conventional care, were studied. Median primary and total length of stay were significantly shorter in the ERAS group (9 vs 12 days; p = 0.0001; 10 vs 12 days; p = 0.01; respectively). The ERAS group experienced a faster recovery of bowel function than the traditional care group (p = 0.0001). A similar morbidity rate was observed in the two groups (32.3 % in ERAS vs 36.1 % in traditional care p = 0.41). Readmission rates were 4.9 % in the ERAS versus 1.5 % in the traditional care group (p = 0.19). There was no mortality in either group. Overall mean compliance with the ERAS protocol was 85.7 % (range 54.4-100 %). CONCLUSIONS: The introduction of the ERAS protocol in laparoscopic rectal resection led to a reduction in primary and total length of hospital stay without an increase in morbidity or readmission rates when compared to traditional care. PMID- 27262310 TI - Antiamnesic properties of analogs and mimetics of the tripeptide human urocortin 3. AB - Amnesia is a deficit in memory caused by brain damage, disease, or trauma. Until now, there are no successful medications on the drug market available to treat amnesia. Short analogs and mimetics of human urocortin 3 (Ucn 3) tripeptide were synthetized and tested for their action against amnesia induced by eletroconvulsion in mice. Among the 16 investigated derivatives of Ucn 3 tripeptide, eight compounds displayed antiamnesic effect. Our results proved that the configuration of chiral center of glutamine does not affect the antiamnesic properties. Alkyl amide or isoleucyl amide at the C-terminus may lead to antiamnesic compounds. As concerned the N-terminus, acetyl, Boc, and alkyl ureido moieties were found among the active analogs, but the free amino function at the N-terminus usually led to an inactive derivatives. These observations may lead to the design and synthesis of small peptidomimetics and amino acid derivatives as antiamnesic drug candidates, although the elucidation of the mechanism of the action requires further investigations. PMID- 27262311 TI - Syndrome of transient headache with neurologic deficits and cerebrospinal fluid lymphocytosis: SPECT usefulness in the diagnosis. PMID- 27262312 TI - Delayed diagnosis of cervical spinal cord transection without radiographic abnormality in a 3-year-old child after a motor vehicle accident. PMID- 27262313 TI - Venous anomaly analogous to vertical embryonic positioning of the straight sinus associated with atretic cephalocele at the suboccipital region. AB - BACKGROUND: The coexistence of venous anomalies, such as vertical embryonic positioning of the straight sinus (VEP of SS), has been reported in patients with atretic cephalocele (AC). VEP of SS has been exclusively encountered when the AC is found above the torcular. CLINICAL PRESENTATION: We report a patient with suboccipital AC associated with venous anomalies analogous to VEP of SS, consisted of the Galenic venous system which did not drain into the straight sinus in the tentorium, but into the falcine sinus instead. Differences with VEP of SS in our case had no anatomical relationship between the falcine sinus and the suboccipital AC and no large cerebrospinal fluid space around the falcine sinus. A detailed neuroradiological examination was helpful for detecting these minute anomalies. PMID- 27262314 TI - Apricot Kernel Oil Ameliorates Cyclophosphamide-Associated Immunosuppression in Rats. AB - The effects of dietary apricot kernel oil (AKO), which contains high levels of oleic and linoleic acids and lower levels of alpha-tocopherol, were evaluated in a rat model of cyclophosphamide-induced immunosuppression. Rats had intraperitoneal injection with cyclophosphamide to induce immunosuppression and were then infused with AKO or normal saline (NS) for 4 weeks. Enzyme-linked immunosorbent assays were used to detect antimicrobial factors in lymphocytes and anti-inflammatory factors in hepatocytes. Hematoxylin & eosin staining was conducted prior to histopathological analysis of the spleen, liver, and thymus. Significant differences were observed between the immune functions of the healthy control group, the normal saline group, and the AKO group. Compared to the normal saline-treated group, lymphocytes isolated from rats administered AKO showed significant improvement in immunoglobulin (Ig)A, IgM, IgG, interleukin (IL)-2, IL 12, and tumor necrosis factor-alpha (TNF-alpha) levels (p < 0.01). Liver tissue levels of malondialdehyde and activities of superoxide dismutase and glutathione peroxidase indicated reduced oxidative stress in rats treated with AKO (p < 0.01). Dietary AKO positively affected rat growth and inhibited cyclophosphamide associated organ degeneration. These results suggested that AKO may enhance the immune system in vivo. These effects may reflect the activities of intermediate oleic and linoleic acid metabolites, which play a vital role in the immune system, and the alpha-tocopherol in AKO may further enhance this phenomenon. Thus, the use of AKO as a nutritional supplement can be proposed to ameliorate chemotherapy-associated immunosuppression. PMID- 27262315 TI - Flow cytometry-assisted quantification of gammaH2AX expression has potential as a rapid high-throughput biodosimetry tool. AB - Large-scale radiological events require immediate and accurate estimates of doses received by victims, and possibly the first responders, to assist in treatment decisions. Although there are numerous efforts worldwide to develop biodosimetric tools to adequately handle triage needs during radiological incidents, such endeavours do not seem to actively involve sub-Saharan Africa which currently has a significant level of nuclear-related activity. To initiate a similar interest in Africa, ex vivo radiation-induced gammaH2AX expression in peripheral blood lymphocytes from fourteen healthy donors was assessed using flow cytometry. While the technique shows potential for use as a rapid high-throughput biodosimetric tool for radiation absorbed doses up to 5 Gy, significant inter-individual differences in gammaH2AX expression emerged. Also, female donors exhibited higher levels of gammaH2AX expression than their male counterparts. To address these shortcomings, gender-based in-house dose-response curves for gammaH2AX induction in lymphocytes 2, 4, and 6 h after X-ray irradiation are proposed for the South African population. The obtained results show that gammaH2AX is a good candidate biomarker for biodosimetry, but might need some refinement and validation through further studies involving a larger cohort of donors. PMID- 27262316 TI - Nonlinear transfer of elements from soil to plants: impact on radioecological modeling. AB - In radioecology, transfer of radionuclides from soil to plants is typically described by a concentration ratio (CR), which assumes linearity of transfer with soil concentration. Nonlinear uptake is evidenced in many studies, but it is unclear how it should be taken into account in radioecological modeling. In this study, a conventional CR-based linear model, a nonlinear model derived from observed uptake into plants, and a new simple model based on the observation that nonlinear uptake leads to a practically constant concentration in plant tissues are compared. The three models were used to predict transfer of (234)U, (59)Ni and (210)Pb into spruce needles. The predictions of the nonlinear and the new model were essentially similar. In contrast, plant radionuclide concentration was underestimated by the linear model when the total element concentration in soil was relatively low, but within the range commonly observed in nature. It is concluded that the linear modeling could easily be replaced by a new approach that more realistically reflects the true processes involved in the uptake of elements into plants. The new modeling approach does not increase the complexity of modeling in comparison with CR-based linear models, and data needed for model parameters (element concentrations) are widely available. PMID- 27262318 TI - Urinary Bladder Paragangliomas: Analysis of Succinate Dehydrogenase and Outcome. AB - Paragangliomas of the urinary bladder can arise sporadically or as a part of hereditary syndromes including those with underlying mutations in the succinate dehydrogenase (SDH) genes, which serve as tumor suppressors. SDH deficiency can be screened for by absence of immunohistochemical detection of SDHB. In this study of 11 cases, clinical follow-up was available for 9/11 cases. The cases were reviewed and graded based on the grading system for adrenal pheochromocytomas and paragangliomas (GAPP) criteria. Immunohistochemistry was performed for Ki67 and SDHB. Proliferative index was calculated by quantification of Ki67-positive cells at hot spots. The medical record was accessed for documentation of germline SDH mutations. Urinary bladder paragangliomas had a female predilection (8/11 cases), and 5/11 cases exhibited metastatic behavior. Patients with metastatic disease tended to be younger (mean age 43 vs 49 years), have larger lesions (5.8 vs 1.5 cm), and presented with catecholamine excess (4/4 vs 2/6 patients with non-metastatic lesions). Patients with metastatic disease had a higher mean Ki67 proliferation rate (4.9 vs 1.3 %) and GAPP score (mean of 5.8 vs 3.8) (p = 0.01). IHC for SDHB expression revealed loss of expression in 2/6 cases of non-metastatic paragangliomas compared to 4/5 patients with metastatic paragangliomas. Interestingly, of these four patients, two had a documented mutation of SDHB, one patient had a SDHC mutation, and another patient had a history of familial disease without mutation analysis being performed. Our study, suggests that SDH loss was suggestive of metastatic behavior in addition to younger age at diagnosis, larger tumor size, and higher Ki67 proliferation rate and catecholamine type. PMID- 27262319 TI - Molecular Targeted Magnetic Resonance Imaging of Human Colorectal Carcinoma (LoVo) Cells Using Novel Superparamagnetic Iron Oxide- Loaded Nanovesicles: In Vitro and in vivo Studies. AB - OBJECTIVE: To investigate the feasibility of superparamagnetic iron oxide (SPIO) nanoparticles (SPIO) as a magnetic resonance (MR) contrast agent to enhance tumor imaging in vivo. METHODS: Hydrophobic SPIO (oil-soluble SPIO; OSPIO) and hydrophilic SPIO (water-soluble SPIO; WSPIO) were loaded in methoxy-poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-PDLLA) nanovesicles. Three groups of nude mice (n=12/group) xenografted with human colorectal carcinoma (LoVo) cells were injected into the caudal vein with WSPIO, OSPIO-loaded nanovesicles, or WSPIO-loaded nanovesicles. MRI scans were performed on all of the mice, and the relative T2 values were measured in the tumor and the liver. The differences in these T2 values between the three groups were compared. RESULTS: The peak relative T2 values in the tumors detected by the OSPIO- or WSPIO-loaded contrast agents were reduced by 10.12% and 11.40%, respectively. The relative T2 values in the WSPIO- and OSPIO-loaded polymeric nanovesicle groups were more pronounced than the relative T2 value in the WSPIO group (P<0.05), but there was no significant difference in the T2 value between the OSPIO- and WSPIO-loaded vesicle groups (P>0.05). The greatest T2 value decreases in the liver in the WSPIO, OSPIO-loaded and WSPIO-loaded vesicle groups were 32.85%, 52.77% and 56.89%, respectively. The decrease in the T2 values was more pronounced in the WSPIO- and OSPIO-loaded nanovesicle groups than in the WSPIO group (P<0.05) and was more apparent in the WSPIO-loaded nanovesicle group than in the OSPIO-loaded nanovesicle group (P<0.05). CONCLUSION: SPIO-loaded polymeric nanovesicles generate significant T2WI signal intensity decreases in vivo and are anticipated to be used as novel and effective contrast agents for tumor imaging. PMID- 27262317 TI - Expanded CD4(+) Effector/Memory T Cell Subset in APECED Produces Predominantly Interferon Gamma. AB - PURPOSE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare human autoimmune disorder caused by mutations in the AIRE (autoimmune regulator) gene. Loss of AIRE disrupts thymic negative selection and gives rise to impaired cytotoxic and regulatory T cell populations. To date, CD4(+) T helper (Th) cells remain little studied. This study aims to elucidate their role in APECED pathogenesis. METHODS: Th cells were explored in ten APECED patients and ten healthy controls using cell culture assays, multiparameter flow cytometry, and transcriptome analysis. RESULTS: The proportions of effector/memory populations were increased while the fraction of naive cells was diminished. The naive population was abnormally activated, with an increased number of cells expressing characteristic Th1, Th2, and Th17 cytokines. No clear deviation to any Th subclass was observed, but transcriptome analysis suggested abnormalities in the Th1 cytokine interferon gamma (IFN-gamma) pathway and flow cytometry showed that INF-gamma had the highest expression. The augmented INF-gamma signaling may promote the function of the putative pathogenic CD8(+) cytotoxic population in the patients. In addition, the frequency of CD4(+) recent thymic emigrants (RTEs) was decreased in the patients, and RTEs also contained cytokine-producing cells at an increased frequency. CONCLUSION: These data reveal abnormalities in the Th population and suggest that they may in part be traced to premature activation already in the thymus. PMID- 27262320 TI - Targeting Key Metabolic Enzymes Involved in Lipid and Protein Biosyntheses for Breast Anticancer Therapies. AB - The evolution of genomic research enabled the genetic and molecular profiling of breast cancer and revealed the profound complexity and heterogeneity of this disease. Subtypes of breast cancer characterized by mutations and/or amplifications of some proto-oncogenes are associated with an increased rate of recurrence and poor prognosis. They represent a challenge in the clinic with limited arsenal to attack them. Nowadays, metabolic reprogramming is firmly established as a hallmark of cancer. An increased rate of lipid and protein syntheses in cancerous tissues, a direct consequence of alterations in key metabolic enzymes involved in these pathways, is now recognized as an important aspect of the rewired metabolism of neoplastic cells. Over the past several years, accumulating evidence has revealed that mutations or amplifications of some proto-oncogenes are primarily involved in this metabolic dysregulation. It is thus critically important to dissect the molecular mechanisms tumors use to link metabolic reprogramming with upstream altered signaling. In this article, we review the recent findings that support the importance of lipid and protein biosyntheses in breast tumorigenesis, discuss the crosstalk between growth factor signal transduction and key metabolic enzymes involved in these processes, and point out the potentials of developing new strategies and therapeutics to target these key parameters in order to help breast cancer patients by providing new therapeutic opportunities. PMID- 27262321 TI - Antihyperlipidemic, Antioxidant and Cytotoxic Activities of Methanolic and Aqueous Extracts of Different Parts of Star Fruit. AB - BACKGROUND: Star fruit (Averrhoa carambola) is a well-known plant in Malaysia which bears a great significance in traditional medicine. OBJECTIVES: This study aimed to evaluate the antihyperlipidemic effect, antioxidant potential and cytotoxicity of aqueous and methanolic extracts of ripe and unripe fruits, leaves and stem of A. carambola. METHODS: Antihyperlipidemic activity was assessed in poloxamer-407 (P-407) induced acute hyperlipidemic rat's model. The antioxidant activity was assessed in vitro using 2, 2'-azino-bis (3-ethylbenzthiazoline-6 sulphonic acid) (ABTS) radical scavenging, 1-diphenyl-2-dipicrylhydrazyl radical scavenging (DPPH) and ferric reducing antioxidant power (FRAP) assays. In addition, cytotoxicity of A. carambola extracts was assessed using MTS assay on four leukemic cell lines (human colon cancer, human promyeloid leukemia, erythroid leukemia, acute myeloid leukemia) and one normal cell (human umbilical vein endothelial cells). RESULTS: Methanolic extract of leaves had the most potent antihyperlipidemic activity in P-407 model, whereby it significantly reduced serum levels of total cholesterol (P<0.01), triglycerides (P<0.01), low density lipoprotein (P<0.05), verylow- density lipoprotein (P<0.01) and atherogenic index (P<0.01). On the other hand, methanolic extracts of A. carambola stem and leaves showed the strongest antioxidant activity. Total phenolic and flavonoid contents of the extracts exhibited significant correlations with antioxidant but not with antihyperlipidemic activities. All plant parts showed no cytotoxic effect on the selected cancer or normal cell lines. CONCLUSION: Antihyperlipidemic activity of different parts of A. carambola is greatly affected by extraction solvents used. Methanolic extract of A. carambola leaves exhibited higher antihyperlipidemic and antioxidant potentials compared to other parts of the plant. PMID- 27262322 TI - Psychoactive substances use and associated factors among middle and high school students in the North Center of Morocco: a cross-sectional questionnaire survey. AB - BACKGROUND: Data on psychoactive substance (PAS) consumption among adolescents in the North Center of Morocco are not at all available. Therefore, the current study aimed at investigating the prevalence and the determinants of psychoactive substances use among middle and high school students in this region. METHODS: A cross-sectional study was conducted from April 2012 to November 2013 in public middle and high schools in the North Central Region of Morocco. An anonymous self administered questionnaire was used to assess psychoactive substances use among a representative sample of school students from the 7th to the 12th grade, aged 11 23 years, selected by stratified cluster random sampling. Factors associated with psychoactive substance use were identified using multivariate stepwise logistic regression analyses. RESULTS: A total of 3020 school students completed the questionnaires, 53.0 % of which were males. The overall lifetime smoking prevalence was 16.1 %. The lifetime, annual and past month rates of any psychoactive substance use among the study subjects were 9.3, 7.5, and 6.3 % respectively. Cannabis recorded the highest lifetime prevalence of 8.1 %, followed by alcohol 4.3 %, inhalants 1.7 %, psychotropic substances without medical prescription 1.0, cocaine 0.7, heroine 0.3, and amphetamine with only 0.2 %. Psychoactive substance use was associated with males more than females. The risk factors identified by multivariate stepwise logistic regression analyses were being male, studying in secondary school level, smoking tobacco, living with a family member who uses tobacco, and feeling insecure within the family. CONCLUSIONS: The prevalence among all school students reported by the current study was comparable to the national prevalence. Efforts to initiate psychoactive substance prevention programs among school students should be made by designing such programs based on the significant factors associated with psychoactive substance use identified in this study. PMID- 27262325 TI - Challenges and Strategies in Precision Medicine for Non-Small-Cell Lung Cancer. AB - Lung cancer is the most common cause of cancer- related death worldwide, causing over 1.2 million deaths each year. Non-small-cell lung cancer (NSCLC) consists of a group of malignancies that are pathologically and molecularly diverse but that are all characterised by a poor prognosis. Survival rates for lung cancer patients have improved very slowly and only to a modest degree owing partly to poor funding for research into this malignancy and stigma associated with smoking, as well as relative chemo-resistance. However, in recent years, NSCLC has become an exemplar for precision medicine, mainly following development of drugs targeting the receptors of epidermal growth factor and anaplastic lymphoma kinase. While epidermal growth factor receptor and anaplastic lymphoma kinase inhibitors are only applicable to a minority of patients and benefits are almost invariably short-lived, current studies indicate that at least 50% of patients with NSCLC have a targetable mutation. With a growing armamentarium of inhibitors against these targets in development, there is a hope that a greater proportion of patients will benefit from precision medicine and that such benefits will be sustained. However, there remain significant challenges in the development of precision medicine in NSCLC. These include: identification and validation of new targets; ensuring biopsies are fit for purpose; tumour heterogeneity; requirements for serial tumour assessments; and not least cost. In this review, we will discuss the current status of precision medicine in NSCLC as well as how basic and translational research are paving the way towards overcoming the above challenges. In addition, we will pay attention to clinical strategies in respect to liquid biopsies and the potential use of extracellular vesicles such as exosomes in cancer therapeutics. PMID- 27262324 TI - Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals. AB - BACKGROUND: Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. METHODS: The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. RESULTS: A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. CONCLUSION: Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals. PMID- 27262326 TI - Exploring Nanotechnologies for the Effective Therapy of Malaria Using Plant-Based Medicines. AB - Malaria is a potentially lethal disease caused by species of the plasmodium parasite. Despite the advances in the interventions for its control and approaches to manage fatality, morbidity and mortality rates associated with malaria are still high. At present, artemisinin-based combination therapy is the first line of treatment. However, there is the need to explore newer approaches as reduced effectiveness and multi-drug resistance (even to artemisinin) has been reported in some regions and is expected to widen in scope. Phytomedicines have shown promise for the management of this debilitating disease and there are abundant resources in most of the areas where this disease is endemic. This report would systematically review the literature, emphasizing the challenges encountered in the control of malaria, active phytochemicals currently utilised in the management, drug delivery approaches as well as the nanotechnology-based systems that could be exploited in its treatment. These phytomedicines, either delivered conventionally or via the use of advanced delivery systems may suggest new strategies towards the better management of malaria. PMID- 27262327 TI - Oral Antiplatelet Treatment in STEMI: Current Practice and Future Considerations. AB - BACKGROUND: Patients with ST-segment elevation myocardial infarction represent a high-risk population and an effective antiplatelet treatment adjunctive to primary percutaneous coronary intervention is of paramount importance. METHODS: This topic will review the current evidence on clinical efficacy and safety of oral antiplatelet therapy in patients with an acute ST-segment elevation myocardial infarction. Unsettled issues and future perspectives for their use in these patients are also discussed. RESULTS: Added to aspirin, clopidogrel, prasugrel and ticagrelor represent viable options regarding oral P2Y12 inhibition, with prasugrel and ticagrelor being preferred over clopidogrel, according to results of large randomized clinical trials. Early clinical efficacy of oral antiplatelet agents in STEMI patients has been questioned, mainly because of their delayed onset of action in the clinical setting of ST-segment elevation myocardial infarction and the recently described adverse effect of morphine on their pharmacodynamic/pharmacokinetic profile. Whether these agents should be administered beyond 1 year after the index event is also under discussion, as there is clinical evidence that prolonged administration may be associated with clinical benefit. CONCLUSION: Use of oral P2Y12 inhibitors in patients with ST segment elevation myocardial infarction still faces questions and future research is needed to establish which, when and how should be administered in this clinical setting. PMID- 27262328 TI - Dual or Single Antiplatelet Therapy After Transcatheter Aortic Valve Implantation? A Systematic Review and Meta-Analysis. AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has undeniably earned a prestigious post in the quiver of interventional cardiologists against symptomatic severe aortic stenosis. Cerebrovascular events are listed within the most frequent complications. METHODS: We performed a systematic search of EMBASE, MEDLINE, and the Cochrane library from inception to March 2016 for the following search terms (transcatheter AND antiplatelet) OR (transcatheter AND antithrombotic) to retrieve studies of dual antiplatelet treatment (DAPT) and single antiplatelet treatment (SAPT) in patients after TAVI to study thrombotic, hemorrhagic and cardiovascular events at 30 days post procedure. From a total of 208 records 4 studies met inclusion criteria. RESULTS: In the included studies, 286 patients were enrolled in the DAPT group and 354 patients in the SAPT group. There was no difference in all-cause mortality, cardiovascular mortality, stroke, and myocardial infraction 30 days post TAVI between DAPT and SAPT. However, patients in the DAPT group had a significantly increased incidence of lethal and major bleeding at 30 days of follow-up and the incidence of the combined end point of stroke, spontaneous MI, all-cause mortality and major bleeding was significantly higher in the DAPT group in comparison to the SAPT group. CONCLUSION: DAPT compared to SAPT in patients after TAVI increases incidence of hemorrhagic events with no benefits in terms of thrombotic events and cardiovascular mortality. However, these data must be interpreted cautiously and the choice of DAPT over SAPT must be based on an individual patient characteristic according to medical practice criteria. PMID- 27262329 TI - Genetics in Anti-Platelet Treatment. AB - Anti-platelet drugs are necessary in treating patients with coronary artery disease, ischemic stroke and peripheral arterial disease. However, despite the use of adequate anti-platelet therapy, some patients will experience a recurrent atherothrombotic vascular event. These patients are characterized as low- or non responders to therapy. Individual responsiveness to anti-platelet therapy as the use of clopidogrel and/or aspirin varies widely among patients. Such an individual variability is mainly determined by environmental and genetic factors. In this review, we focused on the underlying genetic mechanisms that might influence response to anti-platelet drugs. PMID- 27262323 TI - Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases. AB - Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or alpha-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFalpha and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products, and their integration with self-care, music and mHealth, expands precision/personalized medicine strategies for chronic diseases via pharmacological-behavioral combination therapies. PMID- 27262330 TI - Historical Spice as a Future Drug: Therapeutic Potential of Piperlongumine. AB - BACKGROUND: Spice and spice-derived compounds have been identified and explored for their health benefits since centuries. One of the spice long pepper has been traditionally used to treat chronic bronchitis, asthma, constipation, gonorrhea, paralysis of the tongue, diarrhea, cholera, malaria, viral hepatitis, respiratory infections, stomach ache, diseases of the spleen, cough, and tumors. METHODS: In this review, the evidences for the chemopreventive and chemotherapeutic potential of piperlongumine have been described. RESULTS: The active component piperlonguime has shown effective against various ailments including cancer, neurogenerative disease, arthritis, melanogenesis, lupus nephritis, and hyperlipidemic. These beneficial effects of piperlongumine is attributed to its ability to modulate several signaling molecules like reactive oxygen species, kinases, proteasome, proto-oncogenes, transcription factors, cell cycle, inflammatory molecules and cell growth and survival molecules. Piperlongumine also chemosensitizes to drugs resistant cancer cells. CONCLUSION: Overall the consumption of long peppers is therefore recommended for the prevention and treatment of various diseases including cancer, and thus piperlongumine may be a promising future candidate drug against cancer. PMID- 27262331 TI - Phytochemicals as Inhibitors of Candida Biofilm. AB - BACKGROUND: Candida biofilm and associated infections is a serious threat to the large population of immunocompromised patients. Biofilm growth on prosthetic devices or host tissue shows reduced sensitivity to antifungal agents and persists as a reservoir of infective cells. Options for successful treatment of biofilm associated Candida infections are restricted because most of the available antifungal drugs fail to eradicate biofilms. OBJECTIVE: Various plant actives are known to possess interesting antifungal properties. To explore and review the potential of phytochemicals as a novel strategy against Candida biofilms is the intent of present article. METHOD: Thorough literature search is performed to identify Candida biofilm inhibitors of plant origin. An account of efficacy of selected phytochemicals is presented taking into consideration their biofilm inhibitory concentrations. RESULTS: This review discusses biofilm formation by Candida species, their involvement in human infections, and associated drug resistance. It gives insight into the biofilm inhibitory potential of various phytochemicals. Based on the available reports including the work done in our laboratory, several plant extracts, essential oils and phytomolecules have been identified as excellent inhibitors of biofilms of C. albicans and non-albicans Candida species (NACS). CONCLUSION: Selected phytochemicals which exhibit activities at low concentrations without displaying toxicity to host are potential therapeutic agents against biofilm associated Candida infections. In vivo testing in animal models and clinical trials in humans are required to be taken up seriously to propose few of the phytochemicals as candidate drug molecules. PMID- 27262332 TI - Phytochemicals as Adjunctive with Conventional Anticancer Therapies. AB - BACKGROUND: Cancer is defined as the abnormal proliferations of cells which could occur in any tissue and can cause life-threatening malignancies with high financial costs for both patients and health care system. Plant-derived secondary metabolites are shown to have positive role in various diseases and conditions. The aim of the present study is to summarize clinical evidences on the benefits of phytochemicals as adjuvant therapy along with conventional anticancer therapies. METHODS: Electronic databases including Pubmed, Scopus and Cochrane library were searched with the keywords "chemotherapeutic", "anticancer", "antineoplastic" or "radiotherapy" with "plant", "extract", "herb", or "phytochemical", until July 2015. Only clinical studies were included in this review. RESULTS: The findings showed that positive effects of phytochemicals are due to their direct anticarcinogenic activity, induction of relief in cancer complications, as well as their protective role against side effects of conventional chemotherapeutic agents. Results obtained from current review demonstrated that numerous phytochemical agents from different chemical categories including alkaloid, benzopyran, coumarin, carotenoid, diarylheptanoid, flavonoid, indole, polysaccharide, protein, stilbene, terpene, and xanthonoid possess therapeutic effect in patients with different types of cancer. Polyphenols are the most studied components. Curcumin, ginsenosides, lycopene, homoharringtonine, aviscumine, and resveratrol are amongst the major components with remarkable volumes of clinical evidence indicating their direct anticancer activities in different types of cancer including hepatocarcinoma, prostate cancer, leukemia and lymphoma, breast and ovarian cancer, and gastrointestinal cancers. Cannabinoids, cumarin, curcumin, ginsenosides, epigallocatechin gallate, vitexin, and salidroside are phytochemicals with significant alleviative effect on synthetic chemotherapy- induced toxicities. CONCLUSION: There is lack of evidence from clinical trials in case of a large number of phytochemicals and further human studies are recommended to confirm the role of plant metabolites in the management of cancer. PMID- 27262333 TI - Polyketide Natural Products, Acetogenins from Graviola (Annona muricata L), its Biochemical, Cytotoxic Activity and Various Analyses Through Computational and Bio-Programming Methods. AB - BACKGROUND: Plants became the basis of traditional medicine system throughout the world for thousands of years and continue to provide mankind with new remedies. Annona muricata, the plant of Annonaceae family, is also known as sour sop or Graviola. In recent years, many compounds have been reported and have gained organic chemist's and biochemist's attention because of their novel structure and wide range of bioactivity. Local populations have used the bark, leaves, roots, fruit, seeds and flowers for thousands of years to treat everything from arthritis to liver problems. Annonaceous acetogenins found only in the Annonaceae family kill malignant cells of 12 different types of cancer including Breast, Ovarian, Colon, Prostate, Liver, Lung, Pancreatic and Lymphoma. METHODS: Hence, the study was initiated to identify, fractionate and validate compounds of pharmaceutical importance from the leaf extract. Research was made for the phytochemical screening using different solvents and the metabolites were screened using TLC. RESULTS: The presence of acetogenins was confirmed using PMA 5% spray. The anti-cancer activity studies were done for Breast Cancer cell lines, MCF-7 and the cell inhibition activity was 98%. We were curious to study the computational part of the aetogenins; hence, apart from the experimental studies, various computational studies were progressed using Schrodinger and other computational tools to validate the key target protein and the potent molecule "Coronin" and Annonaine. CONCLUSION: To predict and decipher the activity of various acetogenins in Annona muricata and its potent activity towards the inhibition of cancer cell lines, it is interesting to look out for the potent lead compound against the disease. PMID- 27262334 TI - Discriminating Drug-Like Compounds by Partition Trees with Quantum Similarity Indices and Graph Invariants. AB - The search for new drug candidates in databases is of paramount importance in pharmaceutical chemistry. The selection of molecular subsets is greatly optimized and much more promising when potential drug-like molecules are detected a priori. In this work, about one hundred thousand molecules are ranked following a new methodology: a drug/non-drug classifier constructed by a consensual set of classification trees. The classification trees arise from the stochastic generation of training sets, which in turn are used to estimate probability factors of test molecules to be drug-like compounds. Molecules were represented by Topological Quantum Similarity Indices and their Graph Theoretical counterparts. The contribution of the present paper consists of presenting an effective ranking method able to improve the probability of finding drug-like substances by using these types of molecular descriptors. PMID- 27262335 TI - The Impact of Antiplatelet Treatment on Endothelial Function. AB - The vascular endothelium comprises a continuous single cell layer of endothelial cells which line the entire cardiovascular system. Impaired endothelial function underlies the pathogenesis and contributes to the progression of atherosclerosis. Oxidative stress, vasoconstriction, inflammation, proliferation and thrombosis occur in dysfunctional endothelium while the latter, is primarily mediated by platelet activation and adherence to vascular wall. Despite the primary action of antiplatelet agents including aspirin, P2Y12 ADP receptor antagonists and glycoprotein IIb/IIIa inhibitors, a growing body of literature suggests that an important mechanism of their action involves complex modulation of endothelial function via platelet-endothelial interactions, modification of the inflammatory cytokine cascade and nitric oxide mediated effects. These agents represent the mainstay in pharmacological treatment of all aspects of cardiovascular disease both in primary and secondary prevention. However beyond these properties, it is important to note that pharmacological modification of endothelial dysfunction has been postulated as a therapeutic target for reduction of cardiovascular events. PMID- 27262336 TI - Treatment Options for Persistent Coagulase Negative Staphylococcal Bacteremia in Neonates. AB - BACKGROUND: Coagulase-negative staphylococci (CoNS) are the leading cause of late onset sepsis in neonatal intensive-care units (NICUs). Despite adequate therapeutic levels and in vivo susceptibility, vancomycin is not always adequate in clearing CoNS bacteremias and other theurapeutic regimens are warranted especially when dealing with persistent CoNS bacteremias. METHODS: Retrospective analysis of neonates with persistent CoNS bacteremias in a tertiary NICU in two study periods (January 2006 to December 2007 and January 2011 to December 2012). Demographics, clinical characteristics and antibiotics used were recorded. We also performed a literature review on the treatment options for persistent CoNS bacteremia. RESULTS: Out of the 1485 admissions during the 4 years, 121 (8,1%) neonates developed CoNS bacteremia and 42 of them (34.7%) were persistent. The most common CoNS species was S.epidermidis (91%). Apart from the shorter mean duration of bacteremia (p = 0.003), during the second part of the study, no other differences were observed between the two study periods. Ten (23.8%) neonates were treated with vancomycin monotherapy. In 23 (54.7%) neonates, rifampicin was added to vancomycin. Linezolid was given to seven neonates (16.6%), whereas daptomycin was given to two neonates (4.7%). No differences were found when we compared the characteristics of neonates treated with different antibiotics. All neonates tolerated treatment well. Our literature review revealed 16 relevant studies, the majority of which are small case series. CONCLUSION: The addition of rifampicin, linezolid and daptomycin in neonates with persistent CoNS bacteremia can provide useful therapeutic alternatives. Further studies are required to bring more insight into the field. PMID- 27262337 TI - Implications of Kidney Disease on Metabolic Reduction. AB - Chronic kidney disease (CKD) modulates the nonrenal clearance of drugs by altering their metabolism and/or transport. While the effects of CKD on pathways of oxidative and conjugative metabolism in the liver are generally understood, the impact of CKD on hepatic reduction is not. Reduction is a critically important pathway for the metabolism of several drugs and endogenous compounds. Multiple clinical pharmacokinetic studies have reported changes in the disposition of hepatic reductase drug substrates in patients with CKD. More recently, data from experimental studies have shown that kidney disease alters the functional expression of hepatic reductases. Together, these data suggest that kidney disease may impair the nonrenal clearance of drugs mediated by reductive pathways. This review synthesizes the current evidence available regarding the effect of CKD on hepatic reduction. Areas for future investigations are also highlighted. The growing knowledge of the impact of impaired kidney function on nonrenal drug clearance may facilitate optimal drug therapy in this patient population. PMID- 27262338 TI - A live attenuated Salmonella Enteritidis secreting detoxified heat labile toxin enhances mucosal immunity and confers protection against wild-type challenge in chickens. AB - A live attenuated Salmonella Enteritidis (SE) capable of constitutively secreting detoxified double mutant Escherichia coli heat labile toxin (dmLT) was developed. The biologically adjuvanted strain was generated via transformation of a highly immunogenic SE JOL1087 with a plasmid encoding dmLT gene cassette; the resultant strain was designated JOL1641. A balanced-lethal host-vector system stably maintained the plasmid via auxotrophic host complementation with a plasmid encoded aspartate semialdehyde dehydrogenase (asd) gene. Characterization by western blot assay revealed the dmLT subunit proteins in culture supernatants of JOL1641. For the investigation of adjuvanticity and protective efficacy, chickens were immunized via oral or intramuscular routes with PBS, JOL1087 and JOL1641. Birds immunized with JOL1641 showed significant (P <= 0.05) increases in intestinal SIgA production at the 1(st) and 2(nd) weeks post-immunization via oral and intramuscular routes, respectively. Interestingly, while both strains showed significant splenic protection via intramuscular immunization, JOL1641 outperformed JOL1087 upon oral immunization. Oral immunization of birds with JOL1641 significantly reduced splenic bacterial counts. The reduction in bacterial counts may be correlated with an adjuvant effect of dmLT that increases SIgA secretion in the intestines of immunized birds. The inclusion of detoxified dmLT in the strain did not cause adverse reactions to birds, nor did it extend the period of bacterial fecal shedding. In conclusion, we report here that dmLT could be biologically incorporated in the secretion system of a live attenuated Salmonella-based vaccine, and that this construction is safe and could enhance mucosal immunity, and protect immunized birds against wild-type challenge. PMID- 27262339 TI - Development of an innovative decentralized treatment system for the reclamation and reuse of strong wastewater from rural community: Effects of elevated CO2 concentrations. AB - In a previous study, a soil-plant-based natural treatment system was successfully developed for post-treatment of anaerobically digested strong wastewater full of potential nutrients (nitrogen, phosphorus, and potassium). For upgraded performance, an innovative decentralized treatment system was further developed, in which an anaerobic digestion stage and a natural treatment system stage are placed within a greenhouse. This allows the CO2 generated by the processing of wastewater and biogas consumption to be sequestrated within the greenhouse for elevating its concentration level and potentially enhance nutrient removal and recovery from the applied wastewater. To investigate the feasibility of the system, a bench-scale experiment was conducted using CO2 chambers. Valuable Kentucky bluegrass was planted in two soil types (red ball earth and black soil) at three CO2 concentrations (340 ppm, 900 ppm, and 1400 ppm). The results confirmed the positive effects of elevated CO2 concentration on the biomass production and turf quality of Kentucky bluegrass as well as the resulting higher nutrient recovery efficiencies. More importantly, it was demonstrated that the elevated CO2 concentration significantly stimulated the soil nitrifying microorganisms and thus improved the nitrogen removal efficiency (a critical issue in ecological wastewater treatment). A CO2 concentration of 1400 ppm is therefore recommended for use in the system. The mechanism underlying this phenomenon was shown to be an indirect effect, in which the higher CO2 concentration first positively influenced growing plants, which then stimulated the soil nitrifier communities. The effects of soil type (a design parameter) and hydraulic and nutrient loading rates (an operational parameter) on system performance were also examined. The results favored black soil for system establishment. Based on the findings of this study, our proposed system is thought to have the potential to be scaled up and adopted by rural communities worldwide for the reclamation and reuse of strong wastewater, addressing the agricultural non-point source pollution, and achieving the sustainable development. PMID- 27262340 TI - Global direct pressures on biodiversity by large-scale metal mining: Spatial distribution and implications for conservation. AB - Biodiversity loss is widely recognized as a serious global environmental change process. While large-scale metal mining activities do not belong to the top drivers of such change, these operations exert or may intensify pressures on biodiversity by adversely changing habitats, directly and indirectly, at local and regional scales. So far, analyses of global spatial dynamics of mining and its burden on biodiversity focused on the overlap between mines and protected areas or areas of high value for conservation. However, it is less clear how operating metal mines are globally exerting pressure on zones of different biodiversity richness; a similar gap exists for unmined but known mineral deposits. By using vascular plants' diversity as a proxy to quantify overall biodiversity, this study provides a first examination of the global spatial distribution of mines and deposits for five key metals across different biodiversity zones. The results indicate that mines and deposits are not randomly distributed, but concentrated within intermediate and high diversity zones, especially bauxite and silver. In contrast, iron, gold, and copper mines and deposits are closer to a more proportional distribution while showing a high concentration in the intermediate biodiversity zone. Considering the five metals together, 63% and 61% of available mines and deposits, respectively, are located in intermediate diversity zones, comprising 52% of the global land terrestrial surface. 23% of mines and 20% of ore deposits are located in areas of high plant diversity, covering 17% of the land. 13% of mines and 19% of deposits are in areas of low plant diversity, comprising 31% of the land surface. Thus, there seems to be potential for opening new mines in areas of low biodiversity in the future. PMID- 27262342 TI - Type and severity of septal deviation are not related with the degree of subjective nasal obstruction. AB - BACKGROUND: Septoplasty is a frequently performed operation by otolaryngologists to relieve nasal obstruction complaints. When objective measurements tools are not available, preoperative decision-making is based on careful clinical examination. Our aim was to evaluate the relationship between type and severity of septal deviation and patient-reported nasal obstruction. METHODOLOGY: 196 Patients of a general otolaryngology population were included. Patients indicated subjective nasal obstruction experienced during the past 1 month on a Visual Analog Scale (VAS). Patients underwent clinical examination to evaluate type and severity of septal deviation. We compared clinical examination findings with patients VAS. RESULTS: We did not find a statistical difference of VAS score between the different types and severities of septal deviation. In 33.9% of the cases without septal deviation, there was a corresponding VAS score of 0. In 26,8% of the cases with septal deviation, there was no complaint of nasal obstruction (VAS = 0). In 7,4% of the cases, there was moderate to severe nasal obstruction complaint (VAS over 4) though no septal deviation was found. CONCLUSIONS: These results demonstrate that patient-reported nasal obstruction varies greatly among patients with similar type of deviation and similar degree of deviation. Classification of septal deviation into type and severity cannot predict the degree of subjective nasal obstruction. Therefore, the decision to proceed to septoplasty has to be thoughtful, with as much as information, based on the combination of patients history, clinical examination, surgeons experience and cautious interpretation of objective measurement tools. PMID- 27262341 TI - Who benefited from the New Rural Cooperative Medical System in China? A case study on Anhui Province. AB - BACKGROUND: The goal of the New Rural Cooperative Medical System (NCMS) is to decrease the financial burden and improve the health of rural areas. The purpose of the present study is to determine how government subsidies vary between poorer and wealthier groups, especially in low-income regions in rural China. METHODS: The distribution, amount, and equity of government subsidies delivered via NCMS to rural residents at different economic levels were assessed using benefit incidence analysis, concentration index, Kakwani index, Gini index, Lorenz curve, and concentration curve. Household and health institution surveys were conducted in 2010, covering 9701 residents. Household socio-economic status, healthcare costs, out-of-pocket payments, and utilization information were collected in household interviews, and reimbursement policy was provided by institutional survey. RESULTS: The government subsidy concentration index was -0.055 for outpatients and 0.505 for inpatients; and the outpatient and inpatient subsidy Kakwani indexes were -0.376 and 0.184, respectively. The poorest 20 % of populations received 3.4 % of the total subsidy output; while the wealthiest 20 % received 54.3 %. The results showed that the distribution of outpatient subsidies was equitable, but the hospital subsidies disproportionally benefited wealthier people. CONCLUSIONS: Wealthier people benefited more than poorer people from the NCMS in terms of inpatient and total subsidies. For outpatients, the subsidies were unrelated to ability to pay. This contradicts the common belief that the NCMS does not exacerbate benefit inequity. Long-term policy is required to tackle this problem, specifically of redesign the NCMS reimbursement system. PMID- 27262343 TI - Salivary latent trait cortisol (LTC): Relation to lipids, blood pressure, and body composition in middle childhood. AB - Adversity experienced early in life has the potential to influence physical health later in life. The stress-health relation may be partially explained by stress-related effects on cardiovascular risk factors. This study explored links between individual differences in trait-like variation in the activity of the hypothalamic-pituitary-adrenal (HPA) axis with cardiovascular risk factors in children. 474 children (M age=9.22years; 54% female; 83% Caucasian) were included in this study, in which cardiovascular risk was assessed using the following indices - triglycerides (TG), HDL-cholesterol (HDL-C), glucose (Glu); resting systolic and diastolic blood pressure, body mass index (BMI), waist-to-hip ratio, and % fat. Saliva samples were measured 3 times a day (waking, 30min post-waking and bedtime) over 3days (later assayed for cortisol). A latent trait cortisol (LTC) factor explained 43% of the variance in cortisol levels within and across days. Confirmatory factor analysis identified three cardiovascular risk factors: lipids (i.e., TG and HDL-C), blood pressure (i.e., systolic and diastolic), and body composition (i.e., BMI, Waist-to-hip ratio, and % fat). Lower salivary LTC was associated with higher lipids, higher blood pressure, and higher body composition. The findings further support the internal and external validity of the LTC construct, and may also advance our understanding of the link between interindividual differences in HPA axis activity and cardiovascular risk in middle childhood. PMID- 27262344 TI - Basal autonomic activity, stress reactivity, and increases in metabolic syndrome components over time. AB - CONTEXT: Basal autonomic nervous system (ANS) functioning has been linked to the metabolic syndrome (MetS), but the role of ANS reactivity in response to stress remains unclear. OBJECTIVE: To examine cross-sectionally and longitudinally to what extent ANS basal level and stress reactivity are related to MetS. DESIGN: 2 year and 6-year data from a prospective cohort: the Netherlands Study of Depression and Anxiety. SETTING: Participants were recruited from the general community, primary care, and mental health care organizations. PARTICIPANTS: 1922 respondents (mean age=43.7years). MAIN OUTCOME MEASURES: Indicators of ANS functioning were heart rate (HR), respiratory sinus arrhythmia (RSA) and pre ejection period (PEP). ANS stress reactivity was measured during a cognitively challenging stressor and a personal-emotional stressor. MetS components included triglycerides, high-density lipoprotein cholesterol, blood pressure, glucose and waist circumference. RESULTS: Cross-sectional analyses indicated that higher basal HR, lower basal values of RSA and PEP, and higher RSA reactivity during cognitive challenge were related to less favorable values of almost all individual MetS components. Longitudinal analyses showed that higher basal HR and shorter basal PEP predicted 4-year increase in many MetS abnormalities. Higher RSA stress reactivity during cognitive challenge predicted 4-year increase in number of MetS components. CONCLUSION: Higher basal sympathetic, lower basal parasympathetic activity, and increased parasympathetic withdrawal during stress are associated with multiple MetS components, and higher basal sympathetic activity predicts an increase in metabolic abnormalities over time. These findings support a role for ANS dysregulation in the risk for MetS and, consequently, the development of cardiovascular disease. PMID- 27262345 TI - Dysfunctional stress responses in chronic pain. AB - Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-beta, IL-2, IL-6, IL-8, IL-12, IFN-gamma, and TNF-alpha, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. PMID- 27262346 TI - Inflammatory myofibroblastic tumor presenting as ileocecal intussusception-A case report. AB - INTRODUCTION: Inflammatory myofibroblastic tumor (IMFT) is an uncommon mesenchymal solid tumor commonly documented in children and young adults. It is usually located in lungs however, extrapulmonary involvement has also been reported. Here we report a case of IMFT presenting as an ileocecal intussusception. PRESENTATION OF CASE: A 55-year-old man presented with a two months history of colicky abdominal pain, more intense at the right inferior abdominal quadrant, and unintentional weight loss of 8kg in the previous four months. Computer tomography showed an image of intussusception at the cecum. Colonoscopy demonstrated a pediculated tubular lesion, with the base near ileocecal valve. We performed a right hemicolectomy. Histopathological examination of the tumor revealed an IMFT. DISCUSSION: IMFT usually affects lungs with rare gastrointestinal involvement. Clinical presentation is related with location of the neoplasm. Intussusception in adults presents with non-specific symptoms and classical image signs facilitate preoperative diagnosis. IMFT diagnosis is histopathological which usually implies surgical resection. Complete surgical excision, with microscopically clear margins, is the mainstain of treatment, with virtually no local recurrence or metastasis. CONCLUSION: Gastrointestinal IMFT are rare in the adult population and clinical features depend on its location. Surgical approach with total excision of the neoplasm confirms the diagnosis. Prognosis is good with the main prognostic indicator being the adequacy of the primary excision. PMID- 27262347 TI - A primary cellular fibrohistiocytoma of the lung: Report of a case. AB - INTRODUCTION: Cellular fibrohistiocytoma (CFH) is a type of fibrohistiocytic tumor that commonly occurs in the dermis and superficial subcutis. The designation is used for lesions that show increased cellularity with a fascicular growth pattern and frequent extension. Our search of literature only revealed one case of a primary CFH of the lung. We experienced a rare patient with a primary CFH of the lung. PRESENTATION OF CASE: We herein present a rare case of a 77-year old female patient without a cutaneous lesion, who underwent resection for what was considered to be a primary CFH of the lung. There has been no recurrence including a cutaneous lesion in a year after surgery. DISCUSSION: CFH is considered to be benign, but rare cases showing multiple recurrences and involving metastasis to the lymph nodes and internal organs have been reported. At present, it is not possible to predict this aggressive biological behavior based on the tumor histology. CONCLUSION: It is essential to perform resection with an adequate margin with close clinical follow-up. PMID- 27262348 TI - Bilateral V-Y flap for a perianal basal cell carcinoma: A case report. AB - BACKGROUND: Basal cell carcinomas are rare in non-sun-exposed skin, and are even rarer in the perianal region. Alertness to the unusual occurrence of this tumor at perianal site, with understanding of its clinical course, can prevent delay in its diagnosis and morbid aggressiveness in the management of the disease. PRESENTATION OF CASE: A 93 year old female, referred to our hospital because of a three month bleeding ulcerative lesion, with a diameter approximately of 4.5*3.2cm, located in the perianal region. DISCUSSION: Tumors of the anus and perianal are infrequent neoplasms of the digestive tract. There are many diseases that can be confused with this diagnosis and it is commonly delayed because the tumor is rarely thought of in this particular cutaneous topography. Suspicion and early diagnosis, give the opportunity for a timely and appropriate treatment and also prevent tumor extension. CONCLUSION: Treatment modalities include early wide local excision to clear margins, ensuring further local recurrence and distant metastasis. The use of local V-Y advancement fasciocutaneous flaps may be another valid option for the reconstruction of perianal skin defects, with less morbidity than other flaps described in the literature. PMID- 27262349 TI - ECAP analysis in cochlear implant patients as a function of patient's age and electrode-design. AB - INTRODUCTION: Electric compound action potentials (ECAPs) provide information about the nerve's and device's function in and after cochlear implantation. In general, lower ECAP values are expected to generate better results. Aim was an analysis of ECAPs in the course of time as a function of the patient's age and electrode design. PATIENTS AND METHODS: Between 2008 and 2013, 168 patients of eight defined age groups were included into the investigation. NRTs were measured intraoperatively, after 6 and after 12months. RESULTS: The intraoperative mean value of ECAP was 174.14CL (current level) and decreased after 6months to 156.38CL. Highest ECAPs were achieved intraoperatively in the clusters "younger than 18months" (181.04CL) and "older than 80 years" (190.45CL). CI 422 showed apparently higher ECAP thresholds (182.69) during surgery than CI 24 RE (171.47) and CI 512 (170.64). CONCLUSION: ECAPs are a well-established method to get information about the CI's and nerve's function during and after surgery. After initial higher values NRTs decrease after 6months and remain stable in the following controls. Very young and older patients tend to have higher thresholds than middle-aged groups. Perimodiolar electrodes are significantly attached to lower values because there is a closer nerve-electrode interaction. PMID- 27262350 TI - Active inhibition of the first over the second ear implanted sequentially. AB - OBJECTIVE: To identify the influence of the first implanted ear on the performance of the delayed sequentially implanted ear in pediatric patients. STUDY DESIGN: Retrospective case series review. SETTING: Outpatient Cochlear Implant (CI) center. PATIENTS: Congenitally deaf children who underwent unilateral implant at various ages followed by sequential implant of the contralateral ear with various delays were enrolled in the study. Children were divided into two groups based on the retention of the first implant or its removal, creating a sequential unilateral user group (USG) and a sequential bilateral user group (BSG). Both groups reflect differing durations of auditory deprivation in each ear, being relatively longer for the USG group for each ear than for the BSG group. INTERVENTION: Rehabilitative. MAIN OUTCOME MEASURES: All patients underwent periodic speech recognition testing for two years after the second surgery. The results for each implanted ear in both groups were evaluated and an index score representing the Difference Between the Ears, (DBE), was calculated. RESULTS: A statistically significant difference results was obtained between the groups. Both groups reached interaural equivalence (i.e. DBE=0%), after two years post-sequential implant. The USG patients achieved interaural equivalence at a faster rate than the BSG patients with 85% USG subjects demonstrating it at 6months compared to the majority of BSG patients demonstrating equivalence at one-year post-sequential implant. CONCLUSIONS: The performance of the sequentially implanted ear depends to an extent on a negative influence, which could be considered as a type of inhibition, of the first implanted ear over the second ear. It appears that the role of the unilateral auditory deprivation is not the primary influencing factor. These findings have driven us clinically to redefine some important considerations for rehabilitation management of the deaf children in the cases of delayed sequential implant. PMID- 27262351 TI - Death and Plasticity in Clones Influence Invasion Success. AB - Although invasion processes have been intensely studied, the mechanisms underlying the success of some invasive clonal species remain a mystery. Using the specific example of Carpobrotus edulis, we illustrate how invasion success can be facilitated by a unique spatiotemporal regulation of growth and senescence of plant parts. PMID- 27262352 TI - Measurement of corneal tangent modulus using ultrasound indentation. AB - Biomechanical properties are potential information for the diagnosis of corneal pathologies. An ultrasound indentation probe consisting of a load cell and a miniature ultrasound transducer as indenter was developed to detect the force indentation relationship of the cornea. The key idea was to utilize the ultrasound transducer to compress the cornea and to ultrasonically measure the corneal deformation with the eyeball overall displacement compensated. Twelve corneal silicone phantoms were fabricated with different stiffness for the validation of measurement with reference to an extension test. In addition, fifteen fresh porcine eyes were measured by the developed system in vitro. The tangent moduli of the corneal phantoms calculated using the ultrasound indentation data agreed well with the results from the tensile test of the corresponding phantom strips (R(2)=0.96). The mean tangent moduli of the porcine corneas measured by the proposed method were 0.089+/-0.026MPa at intraocular pressure (IOP) of 15mmHg and 0.220+/-0.053MPa at IOP of 30mmHg, respectively. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) of tangent modulus were 14.4% and 0.765 at 15mmHg, and 8.6% and 0.870 at 30mmHg, respectively. The preliminary study showed that ultrasound indentation could be applied to the measurement of corneal tangent modulus with good repeatability and improved measurement accuracy compared to conventional surface displacement-based measurement method. The ultrasound indentation can be a potential tool for the corneal biomechanical properties measurement in vivo. PMID- 27262353 TI - A Volterra series-based method for extracting target echoes in the seafloor mining environment. AB - The purpose of this research was to evaluate the applicability of the Volterra adaptive method to predict the target echo of an ultrasonic signal in an underwater seafloor mining environment. There is growing interest in mining of seafloor minerals because they offer an alternative source of rare metals. Mining the minerals cause the seafloor sediments to be stirred up and suspended in sea water. In such an environment, the target signals used for seafloor mapping are unable to be detected because of the unavoidable presence of volume reverberation induced by the suspended sediments. The detection of target signals in reverberation is currently performed using a stochastic model (for example, the autoregressive (AR) model) based on the statistical characterisation of reverberation. However, we examined a new method of signal detection in volume reverberation based on the Volterra series by confirming that the reverberation is a chaotic signal and generated by a deterministic process. The advantage of this method over the stochastic model is that attributions of the specific physical process are considered in the signal detection problem. To test the Volterra series based method and its applicability to target signal detection in the volume reverberation environment derived from the seafloor mining process, we simulated the real-life conditions of seafloor mining in a water filled tank of dimensions of 5*3*1.8m. The bottom of the tank was covered with 10cm of an irregular sand layer under which 5cm of an irregular cobalt-rich crusts layer was placed. The bottom was interrogated by an acoustic wave generated as 16MUs pulses of 500kHz frequency. This frequency is demonstrated to ensure a resolution on the order of one centimetre, which is adequate in exploration practice. Echo signals were collected with a data acquisition card (PCI 1714 UL, 12-bit). Detection of the target echo in these signals was performed by both the Volterra series based model and the AR model. The results obtained confirm that the Volterra series based method is more efficient in the detection of the signal in reverberation than the conventional AR model (the accuracy is 80% for the PIM-Volterra prediction model versus 40% for the AR model). PMID- 27262354 TI - Integrating molecular epidemiology and social network analysis to study infectious diseases: Towards a socio-molecular era for public health. AB - The number of public health applications for molecular epidemiology and social network analysis has increased rapidly since the improvement in computational capacities and the development of new sequencing techniques. Currently, molecular epidemiology methods are used in a variety of settings: from infectious disease surveillance systems to the description of disease transmission pathways. The latter are of great epidemiological importance as they let us describe how a virus spreads in a community, make predictions for the further epidemic developments, and plan preventive interventions. Social network methods are used to understand how infections spread through communities and what the risk factors for this are, as well as in improved contact tracing and message-dissemination interventions. Research is needed on how to combine molecular and social network data as both include essential, but not fully sufficient information on infection transmission pathways. The main differences between the two data sources are that, firstly, social network data include uninfected individuals unlike the molecular data sampled only from infected network members. Thus, social network data include more detailed picture of a network and can improve inferences made from molecular data. Secondly, network data refer to the current state and interactions within the social network, while molecular data refer to the time points when transmissions happened, which might have happened years before the sampling date. As of today, there have been attempts to combine and compare the data obtained from the two sources. Even though there is no consensus on whether and how social and genetic data complement each other, this research might significantly improve our understanding of how viruses spread through communities. PMID- 27262356 TI - Genetic diversity and population structure of Plasmodium falciparum over space and time in an African archipelago. AB - The archipelago of Sao Tome and Principe (STP), West Africa, has suffered the heavy burden of malaria since the 16th century. Until the last decade, when after a successful control program STP has become a low transmission country and one of the few nations with decreases of more than 90% in malaria admission and death rates. We carried out a longitudinal study to determine the genetic structure of STP parasite populations over time and space. Twelve microsatellite loci were genotyped in Plasmodium falciparum samples from two islands collected in 1997, 2000 and 2004. Analysis was performed on proportions of mixed genotype infections, allelic diversity, population differentiation, effective population size and bottleneck effects. We have found high levels of genetic diversity and minimal inter-population genetic differentiation typical of African continental regions with intense and stable malaria transmission. We detected significant differences between the years, with special emphasis for 1997 that showed the highest proportion of samples infected with P. falciparum and the highest mean number of haplotypes per isolate. This study establishes a comprehensive genetic data baseline of a pre-intervention scenario for future studies; taking into account the most recent and successful control intervention on the territory. PMID- 27262355 TI - The global spread of HIV-1 subtype B epidemic. AB - Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors. PMID- 27262357 TI - Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration. AB - In the previous study, we demonstrated that dichlorvos induces oxidative stress in dopaminergic neuronal cells and subsequent caspase activation mediates apoptosis. In the present study, we evaluated the effect and mechanism of dichlorvos induced oxidative stress on cell cycle activation in NGF differentiated PC12 cells. Dichlorvos exposure resulted in oxidative DNA damage along with activation of cell cycle machinery in differentiated PC12 cells. Dichlorvos exposed cells exhibited an increased expression of p53, cyclin-D1, pRb and decreased expression of p21suggesting a re-entry of differentiated cells into the cell cycle. Cell cycle analysis of dichlorvos exposed cells revealed a reduction of cells in the G0/G1 phase of the cell cycle (25%), and a concomitant increase of cells in S phase (30%) and G2/M phase (43.3%) compared to control PC12 cells. Further, immunoblotting of cytochrome c, Bax, Bcl-2 and cleaved caspase-3 revealed that dichlorvos induces a caspase-dependent cell death in PC12 cells. These results suggest that Dichlorvos exposure has the potential to generate oxidative stress which evokes activation of cell cycle machinery leading to apoptotic cell death via cytochrome c release from mitochondria and subsequent caspase-3 activation in differentiated PC12 cells. PMID- 27262358 TI - Recent Patents for the Treatment of Asthma. AB - BACKGROUND: Despite adequate adherence and completion of anti-asthmatic treatment, many patients remain poorly controlled or uncontrolled. Asthma management is based on the use of medication to reverse the bronchial obstruction and eliminate the airway inflammation. New drug development is expected in the future as a consequence of discoveries in the pathophysiology and mechanisms of asthma. Currently, a good and effective set of treatments is available for these diseases. However, the search for new treatment modalities to improve the currently available is especially important for those patients unresponsive to current therapy. OBJECTIVE: In this review, we summarize new anti-cytokines therapies, anti-leucotrienes molecules, immunomodulatory and anti-inflammatory agents, researched for treatment of asthma. METHOD: Database patents were used for searching new patents from 2015 and from the beginning of 2016 about treatment of asthma. CONCLUSION: Pharmacogenomic point of view is now being considered by most major pharmaceutical companies as line of investigation without end in the nearest horizon. Pharmacogenomics has the potential to notably improve the safety and effectiveness of medications. PMID- 27262359 TI - Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter. AB - PURPOSE: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. METHODS AND MATERIALS: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point gamma analysis. The deviation of the results was used to inform future action levels. RESULTS: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of DeltaD of 0 +/ 5 cGy or %DeltaD of 0% +/- 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% +/- 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (-2 +/- 5 cGy) or summed field percentage dose difference (-6% +/- 7%). CONCLUSIONS: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups. PMID- 27262360 TI - Vibrio ishigakensis sp. nov., in Halioticoli clade isolated from seawater in Okinawa coral reef area, Japan. AB - Five novel strains showing non-motile, alginolytic, halophilic and fermentative features were isolated from seawater samples off Okinawa in coral reef areas. These strains were characterized by an advanced polyphasic taxonomy including genome based taxonomy using multilocus sequence analysis (MLSA) and in silico DNA DNA similarity (in silico DDH). Phylogenetic analyses on the basis of 16S rRNA gene sequences revealed that the isolates could be assigned to the genus Vibrio, however they were not allocated into any distinct cluster with known Vibrionaceae species. MLSA based on eight protein-coding genes (gapA, gyrB, ftsZ, mreB, pyrH, recA, rpoA, and topA) showed the vibrios formed an outskirt branch of Halioticoli clade. The experimental DNA-DNA hybridization data revealed that the five strains were in the range of being defined as conspecific but separate from nine Halioticoli clade species. The G+C contents of the Vibrio ishigakensis strains were 47.3-49.1mol%. Both Amino Acid Identity and Average Nucleotide Identity of the strain C1(T) against Vibrio ezurae HDS1-1(T), Vibrio gallicus HT2-1(T), Vibrio halioticoli IAM 14596(T), Vibrio neonatus HDD3-1(T) and Vibrio superstes G3-29(T) showed less than 95% similarity. The genome-based taxonomic approach by means of in silico DDH values also supports the V. ishigakensis strains being distinct from the other known Halioticoli clade species. Sixteen traits (growth temperature range, DNase and lipase production, indole production, and assimilation of 10 carbon compounds) distinguished these strains from Halioticoli clade species. The names V. ishigakensis sp. nov. is proposed for the species of Halioticoli clade, with C1(T) as the type strain (JCM 19231(T)=LMG 28703(T)). PMID- 27262361 TI - Exploring the learning curve for minimally invasive sutureless aortic valve replacement. AB - OBJECTIVE: The study objective was to assess the learning process and quality of care of right minithoracotomy aortic valve replacement with a sutureless bioprosthesis at a single institution. METHODS: We performed an analysis of the first 300 consecutive patients (aged 76 +/- 6 years; logistic European System for Cardiac Operative Risk Evaluation 9 +/- 6) who underwent sutureless valve implantation via a right minithoracotomy by 6 surgeons at the G. Pasquinucci Heart Hospital between 2011 and 2015. The learning curve was analyzed by dividing the study population into tertiles of 100 patients each. Departmental and individual learning curves were calculated using sequential probability cumulative sum failure analysis. Quality indicators were 2 composite end points reflecting the technical success and 30-day complications. RESULTS: The overall mortality was 0.7% (2 patients). No significant differences were noted in terms of mortality and complications between tertiles. The sutureless valve was implanted successfully in 99% of patients (298/300). Cumulative sum analysis failed to identify any significant learning effects for technical success. Nevertheless, surgeons A, B, and C had a small initial learning curve, and surgeons D, E, and F did not, reflecting a trend toward a positive effect of cumulative institutional experience on the individual learning curve. The 30-day complications analysis revealed a cluster of failures at the beginning of the experience. This cluster prompted an internal audit and modification of the patients' selection process. Consecutively, the procedure returned in control. CONCLUSIONS: Right minithoracotomy sutureless valve implantation can be performed safely without learning curve effects. Cumulative sum analysis is a valuable tool to describe and monitor the learning process. The analysis can identify periods of less than expected performance and alert the team to react. PMID- 27262362 TI - Survival status and functional outcome of children who required prolonged intensive care after cardiac surgery. AB - BACKGROUND: Children who require prolonged intensive care after cardiac surgery are at risk of high mortality. The long-term survival and functional outcome of these children have not been studied in detail. METHODS: Children who stayed in intensive care for >28 days after cardiac surgery from 1997 to 2012 were studied in a single institution. A total of 116 patients were identified; 107 (92%) were <1 year of age and 63 (54%) had univentricular physiology. RESULTS: The incidence of children requiring prolonged intensive care increased from 1.01/100 undergoing cardiac surgery in 1997 to 2000 to 2.66/100 in 2009 to 2012 (P trend = .002). This increase coincided with an increase in the number of children with hypoplastic left heart syndrome having prolonged intensive care during the same period (0.13/100 in 1997-2000 to 1.0/100 in 2009-2012; P trend = .001). Survival to pediatric intensive care unit (PICU) discharge was 74% (95% confidence interval [CI], 65-82) and 51% (95% CI, 41-59) at 3 years. Factors associated with mortality were univentricular repair (hazard ratio [HR], 2.12; 95% CI, 1.21-3.70; P = .008) and acute renal failure (HR, 3.01; 95% CI, 1.77-5.12; P < .001), but era did not influence mortality (1997-2005 vs 2006-2012; log-rank P = .66). Among PICU survivors, 3-year survival in those who did not need early reoperation was 81% (95% CI, 66-90), compared with 58% (95% CI, 42-71) in those who required early reoperation (log-rank P = .01). Among survivors, 36% had either moderate or severe disability and 13% had poor quality of life. CONCLUSIONS: The incidence of children requiring prolonged intensive care after cardiac surgery has increased in our institution. Our data suggest that the long-term outcome for most of these children is poor, especially after univentricular repair. PMID- 27262363 TI - The Spanish standard patch test series: 2016 update by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). AB - The Spanish standard patch test series, as recommended by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC), has been updated for 2016. The new series replaces the 2012 version and contains the minimum set of allergens recommended for routine investigation of contact allergy in Spain from 2016 onwards. Four haptens -clioquinol, thimerosal, mercury, and primin- have been eliminated owing to a low frequency of relevant allergic reactions, while 3 new allergens -methylisothiazolinone, diazolidinyl urea, and imidazolidinyl urea- have been added. GEIDAC has also modified the recommended aqueous solution concentrations for the 2 classic, major haptens methylchloroisothiazolinone and methylisothiazolinone, which are now to be tested at 200ppm in aqueous solution, and formaldehyde, which is now to be tested in a 2% aqueous solution. Updating the Spanish standard series is one of the functions of GEIDAC, which is responsible for ensuring that the standard series is suited to the country's epidemiological profile and pattern of contact sensitization. PMID- 27262365 TI - An international observational study suggests that artificial intelligence for clinical decision support optimizes anemia management in hemodialysis patients. AB - Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targets and individual variability. Because therapy recommendations provided by a decision support system can benefit both patients and doctors, we evaluated the impact of an artificial intelligence decision support system, the Anemia Control Model (ACM), on anemia outcomes. Based on patient profiles, the ACM was built to recommend suitable erythropoietic-stimulating agent doses. Our retrospective study consisted of a 12-month control phase (standard anemia care), followed by a 12-month observation phase (ACM-guided care) encompassing 752 patients undergoing hemodialysis therapy in 3 NephroCare clinics located in separate countries. The percentage of hemoglobin values on target, the median darbepoetin dose, and individual hemoglobin fluctuation (estimated from the intrapatient hemoglobin standard deviation) were deemed primary outcomes. In the observation phase, median darbepoetin consumption significantly decreased from 0.63 to 0.46 MUg/kg/month, whereas on-target hemoglobin values significantly increased from 70.6% to 76.6%, reaching 83.2% when the ACM suggestions were implemented. Moreover, ACM introduction led to a significant decrease in hemoglobin fluctuation (intrapatient standard deviation decreased from 0.95 g/dl to 0.83 g/dl). Thus, ACM support helped improve anemia outcomes of hemodialysis patients, minimizing erythropoietic-stimulating agent use with the potential to reduce the cost of treatment. PMID- 27262364 TI - An NLRP3-specific inflammasome inhibitor attenuates crystal-induced kidney fibrosis in mice. AB - Intrarenal crystal formation activates the Nlrp3 inflammasome in myeloid cells and triggers a profound inflammatory response. Here, we studied whether a specific inhibitor of the Nlrp3 inflammasome, CP-456,773, can prevent kidney fibrosis in a murine model of crystal nephropathy induced by diets rich in oxalate or adenine. Inflammasome activation in renal dendritic cells and the resulting interleukin (IL)-1beta and IL-18 production were markedly reduced by CP 456,773 treatment both ex vivo and in vivo. We directly visualized intrarenal inflammasome activation and its inhibition by CP-456,773 in vivo by adoptive transfer of bone marrow cells transduced with interleukin-1beta-Gaussia luciferase, a proteolytic luciferase-based reporter for inflammasome activation, into irradiated mice. CP-456,773 treatment strongly attenuated kidney fibrosis when given early in the genesis of crystal nephropathy, but was unable to reverse established crystal-induced fibrosis. The urinary IL-18 concentration appeared to be a useful noninvasive biomarker for renal inflammasome activation. Finally, NLRP3 inhibition did not compromise adaptive immune responses as previously reported for the global inhibition of IL-1 signaling. Thus, early NLRP3 inhibition by CP-456,773 may be an effective treatment for crystal nephropathy. Use of iGLuc transfected cells introduces a novel imaging technique for inflammasome activation in mice. PMID- 27262367 TI - Relationship between HHV8 infection markers and insulin sensitivity in ketosis prone diabetes. AB - BACKGROUND AND OBJECTIVES: Peripheral tissue resistance to insulin action is a characteristic of type 2 diabetes mellitus (T2DM). It has also been reported that some chronic viral infections can contribute to insulin resistance. Human herpesvirus (HHV)-8 infection has been detected in T2DM patients in previous studies. Our study investigated whether the presence of the virus is associated with insulin resistance in patients with ketosis-prone type 2 diabetes (KPD), as reported with other viruses. RESEARCH DESIGN AND METHODS: A total of 11 insulin free KPD patients positive (+) and seven patients who were negative (-) for HHV-8 infection were recruited; the latter had KPD that was well controlled (HbA1c=6.2+/-0.7%). A two-step euglycaemic-hyperinsulinaemic clamp test coupled with deuterated [6,6-2H2]glucose was used to assess insulin sensitivity, non esterified fatty acid (NEFA) suppression and endogenous glucose production. RESULTS: In KPD patients, whether HHV-8+ or HHV-8-, there were no differences in NEFA release, endogenous glucose production or insulin sensitivity (M value). CONCLUSION: Asymptomatic HHV-8 infection does not appear to be associated with decreased insulin sensitivity in diabetic patients. These results should now be confirmed in a larger sample population. PMID- 27262366 TI - Clinical, biopsy, and mass spectrometry characteristics of renal apolipoprotein A IV amyloidosis. AB - Apolipoprotein A-IV associated amyloidosis (AApoAIV amyloidosis) is a rare cause of amyloidosis with only a single reported case. Here we describe the clinical, biopsy, and mass spectrometry characteristics of 11 cases of renal AApoAIV amyloidosis encompassing 9 men and 2 women with a mean age at diagnosis of 63.5 years. Progressive chronic kidney disease (mean serum creatinine 2.9 mg/dl) was the most common cause for biopsy with proteinuria absent or minimal in all except one. Hematological and serological evaluation was negative in 9 patients, while 2 had a monoclonal gammopathy. The renal biopsy findings were striking and showed large amounts of eosinophilic Congo-red positive amyloid deposits restricted to the renal medulla with sparing of the renal cortex. In 6 cases, peritubular amyloid was noted in addition to the interstitial involvement. Immunofluorescence studies were negative for immunoglobulins. Electron microscopy showed nonbranching fibrils measuring 7 to 10 nm in diameter. Laser microdissection of the amyloid deposits followed by mass spectrometry showed large spectra number (a semiquantitative measure of abundance) for AApoAIV protein ranging from 49 to 169 (average 85), serum amyloid protein (average 19), and apolipoprotein E (average 48). Importantly, no peptides were detected for any other forms of known amyloidogenic precursor proteins. Thus, renal AApoAIV amyloidosis typically presents with progressive chronic kidney disease and histologically exhibits extensive medullary involvement with sparing of the cortex. The diagnosis is best established by mass spectrometry. Hence, a high degree of suspicion and examination of the renal medulla is required to make the diagnosis. PMID- 27262368 TI - The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women. AB - AIM: Vitamin D deficiency has been proposed to be involved in obesity-induced metabolic disease. However, data on the relationship between 25 hydroxycholecalciferol (25(OH)D) and insulin resistance have been inconsistent, and few studies have investigated the active vitamin D metabolite, 1,25 dihydroxycholecalciferol (1,25(OH)2D). This study aimed to determine the relationship between circulating levels of both 25(OH)D and 1,25(OH)2D and direct measures of glucose metabolism and insulin action in obese women. METHODS: Serum levels of 25(OH)D and 1,25(OH)2D, and glucose metabolism and tissue-specific insulin action, as assessed in the basal state and during a two-step euglycaemic hyperinsulinaemic clamp study with [6,6-2H2]glucose infusion, were measured in 37 morbidly obese women (age: 43+/-10 years; body mass index: 44+/-6kg/m2). RESULTS: Sixteen subjects had circulating 25(OH)D levels<50nmol/L, consistent with vitamin D deficiency, and 21 had normal 25(OH)D levels. There were no differences in either baseline characteristics or parameters of glucose metabolism and insulin action between the groups. Serum 25(OH)D, but not 1,25(OH)2D, was negatively correlated with both body mass index (r=-0.42, P=0.01) and total body fat (r= 0.46, P<0.01). Neither 25(OH)D nor 1,25(OH)2D levels were related to any measured metabolic parameters, including fasting glucose, fasting insulin, basal endogenous glucose production, and hepatic, adipose-tissue and skeletal muscle insulin sensitivity. CONCLUSION: Obesity was associated with lower levels of circulating 25(OH)D, but not with the hormonally active metabolite 1,25(OH)2D. Neither 25(OH)D nor 1,25(OH)2D were related to glucose metabolism and tissue specific insulin sensitivity in obese women, suggesting that vitamin D does not play a major role in obesity-related insulin resistance. PMID- 27262370 TI - Histopathologic Characteristics of Upper Tract Urothelial Carcinoma With an Emphasis on Their Effect on Cancer Survival: A Single-Institute Experience With 305 Patients With Long-Term Follow-Up. AB - INTRODUCTION: Tumor stage and grade represent the best established predictors for the prognosis of upper tract urothelial carcinoma (UTUC). However, controversies still exist regarding the role of tumor necrosis, location, and multifocality in the prognosis of UTUC. We share our experience with 305 patients, reporting on the pathologic features in detail, cancer characteristics, and survival. MATERIALS AND METHODS: We retrospectively reviewed the data from patients who had undergone surgery for UTUC from 1983 to 2013. The tumors were staged according to the 1997 TNM classification and the 3-tiered World Health Organization grading system. Cancer-specific survival (CSS) was estimated using the Kaplan-Meier method. RESULTS: A total of 305 patients were eligible for analysis. The 5-year CSS for grade 1, 2, and 3 was 88%, 84%, and 60%, respectively. The CSS for stage pT1, T2, T3, and T4 was 82%, 70%, 62%, and 0%, respectively. On univariate analysis, tumor stage, tumor grade, positive lymph node status, and micropapillary invasion had adverse effects on survival (P = .006, P = .045, P = .01, and P = .005, respectively). On multivariate analysis, only stage and micropapillary variant maintained significance (P = .01). Multicentricity and tumor location affected CSS in the early follow-up period but did not in the late follow-up period. Neither carcinoma in situ nor adverse pathologic variants affected survival. CONCLUSION: The tumor stage and presence of a micropapillary variant are of paramount prognostic significance for survival in patients with UTUC. The tumor grade and lymph node status are also good predictors. In our series, multifocality and tumor location affected early and mid-term survival with no significant effects on late survival. PMID- 27262369 TI - Impact of Prior Platinum-Based Therapy on Patients Receiving Salvage Systemic Treatment for Advanced Urothelial Carcinoma. AB - BACKGROUND: Trials of salvage therapy for advanced urothelial carcinoma have required prior platinum-based therapy. This practice requires scrutiny because non-platinum-based first-line therapy may be offered to cisplatin-ineligible patients. PATIENTS AND METHODS: Data of patients receiving salvage systemic chemotherapy were collected. Data on prior first-line platinum exposure were required in addition to treatment-free interval, hemoglobin, Eastern Cooperative Oncology Group performance status, albumin, and liver metastasis status. Cox proportional hazard regression was used to evaluate their association with overall survival (OS) after accounting for salvage single-agent or combination chemotherapy. RESULTS: Data were obtained from 455 patients previously exposed to platinum-based therapy and 37 not exposed to platinum. In the group exposed to prior platinum therapy, salvage therapy consisted of a single-agent taxane (n = 184) or a taxane-containing combination chemotherapy (n = 271). In the group not exposed to prior platinum therapy, salvage therapy consisted of taxane or vinflunine (n = 20), 5-fluorouracil (n = 1), taxane-containing combination chemotherapy (n = 12), carboplatin-based combinations (n = 2), and cisplatin based combinations (n = 2). The median OS for the prior platinum therapy group was 7.8 months (95% confidence interval, 7.0, 8.1), and for the group that had not received prior platinum therapy was 9.0 months (95% confidence interval, 6.0, 11.0; P = .50). In the multivariable analysis, prior platinum therapy versus no prior platinum exposure did not confer an independent impact on OS (hazard ratio, 1.10; 95% confidence interval, 0.75, 1.64; P = .62). CONCLUSION: Prior platinum- versus non-platinum-based chemotherapy did not have a prognostic impact on OS after accounting for major prognostic factors in patients receiving salvage systemic chemotherapy for advanced urothelial carcinoma. Lack of prior platinum therapy should not disqualify patients from inclusion onto trials of salvage therapy. PMID- 27262371 TI - Determination of methacrylic acid in food simulants by pyrolytic butylation-gas chromatography. AB - An on-line pyrolytic butylation approach was proposed to determine methacrylic acid (MA) in food simulants by gas chromatography (GC) without an expensive pyrolyzer. MA in food simulants was converted into butyl methacrylate in the presence of tetrabutylammonium hydroxide (TBAH) without any pretreatment at 330 degrees C in the injection-port, contributing to high GC signal response. The derivatizing conditions for the proposed method were optimized, namely the injection-port temperature, type and amount of the organic alkaline used for derivatization. A series of standard solutions of MA in the range of 1.0-50mg/kg were analyzed with correlation coefficient r>=0.9975. The limits of detection (LODs) were less than 0.15mg/kg for MA in four matrix simulants (distilled water, 3%w/v acetic acid, 10%v/v ethanol, and isooctane). Relative standard deviations (RSDs) for retention time, peak height and peak area were all less than 3.88%. The technique was successfully applied to the analysis of MA migrating from plastic cup samples, with recoveries of added MA in the range of 96.5-123.0%. Direct injection of the simulants into the GC system after migration tests, without any pretreatment step, makes the developed method of great value for rapid screening analysis of samples in bulks. PMID- 27262372 TI - Simultaneous quantification of 50 bioactive compounds of the traditional Chinese medicine formula Gegen-Qinlian decoction using ultra-high performance liquid chromatography coupled with tandem mass spectrometry. AB - The quality evaluation of patent drugs derived from traditional Chinese medicine (TCM) compound formulas has been challenging due to their complex chemical composition. In this study, we developed a solution to evaluate the quality of Gegen-Qinlian Decoction (GQD), an ancient four-herb TCM formula for the treatment of diarrhea and diabetes, together with its derived patent drugs by simultaneously quantifying 50 bioactive compounds. The samples were extracted by 100% methanol (for hydrophobic compounds) and 50% methanol in water (for hydrophilic compounds), respectively, and were separated on a Waters Acquity charged surface hybrid C18 column (2.1*100mm, 1.7MUm) eluted with gradients of acetonitrile and water containing 0.1% formic acid at a flow rate of 400MUL/min. The analytes were determined by ultra-high performance liquid chromatography coupled with tandem mass spectrometry in the selected reaction monitoring mode. The 50 compounds (including acidic and alkaline, hydrophilic and hydrophobic) were well resolved within 14min, and were determined using an internal standard method. The method was fully validated for precision, repeatability, and recovery. The limits of detection were 0.3-10.0ng/mL. Finally, this method was used to analyze 24 batches of GQD samples, including water decoction, pills, tablets, and oral solutions. Principal component analysis indicated significantly varied chemical compositions among these formulations. The tablets and pills contained higher concentrations of Scutellaria and Coptis compounds than the oral solutions, and the water decoction contained abundant glycosides and saponins. Moreover, the contents of flavanones and flavone O-glucuronides varied remarkably. This study provides a feasible solution for the comprehensive quality control of TCM patent drugs. PMID- 27262373 TI - Analytical and preparative enantioseparation and main chiroptical properties of Iridium(III) bis(4,6-difluorophenylpyridinato)picolinato. AB - Almost all Iridium(III) complexes employed both as dopants in PhOLEDs and as pharmaceuticals and fluorescence bioprobes are racemic mixtures. In this study the single enantiomers of the most stable diastereomeric form fac-trans-N-N, bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) were separated and analysed. The data obtained showed that the complex can be separated into stable optically active Lambda and Delta isomers employing cellulose based chiral stationary phase both in normal and polar phase mode. Their chirality was confirmed and their absolute configuration assigned employing several methods (DFT and TDDFT calculations, CD and VCD). The CPL spectroscopy of the isolated enantiomers of FIrpic was also recorded due to its possible value in the OLEDs field. The chromatographic method was applied for a semipreparative purpose demonstrating that polar organic solvent chromatography (POSC) could be used to avoid the low-solubility issues associated with these Iridium(III) complexes. Finally, the chemical and stereochemical stability of the single isomers was evaluated under thermal stress by liquid chromatography coupled to high-resolution mass spectrometry (LC-QTOF) on both chiral and achiral columns. No racemization and/or isomerization was observed; however, the dissociation of the ancillary ligand was demonstrated employing LC-QTOF. PMID- 27262374 TI - A review of methods for nematode identification. AB - Nematodes are non-segmented roundworms found in soil, aquatic environment, plants, or animals. Either useful or pathogenic, they greatly influence environmental equilibrium, human and animal health, as well as plant production. Knowledge on their taxonomy and biology are key issues to answer the different challenges associated to these organisms. Nowadays, most of the nematode taxonomy remains unknown or unclear. Several approaches are available for parasite identification, from the traditional morphology-based techniques to the sophisticated high-throughput sequencing technologies. All these techniques have advantages or drawbacks depending on the sample origin and the number of nematodes to be processed. This review proposes an overview of all newly available methods available to identify known and/or unknown nematodes with a specific focus on emerging high-throughput molecular techniques. PMID- 27262375 TI - Development and evaluation of different complex media for phytoplasma isolation and growth. AB - The focus of this research was the development and evaluation of different complex liquid and solid media for the isolation and growth of phytoplasma strains infecting grapevine plants. Previously reported media supporting phytoplasma isolation are commercial and not easy to modify in order to improve performance and selectivity towards obtaining pure cultures of 'Candidatus Phytoplasma' species. Three media (Piv(r), CB and MB) were therefore evaluated for phytoplasma isolation and colony formation under microaerophilic growing conditions, using grapevine canes from plants showing yellows symptoms, and infected by "flavescence doree", "bois noir" and aster yellows phytoplasmas as sources. The newly developed methodology was applied for two years at three sample collection times. Broad applicability and a good repeatability in supporting phytoplasma colony formation were obtained in Pivs(r) and CBs media. While the MB medium did not support phytoplasma isolation and growth, the CB media support a phytoplasma growth comparable to the one obtained in the previously reported media. This medium has the advantage of a formulation that allow its modification to implement specificity towards selective phytoplasma growth. Moreover preliminary trials on serial dilutions and tetracycline addition confirmed some phytoplasma growth behaviours. PMID- 27262376 TI - Erythropoietin increases macrophage-mediated T cell suppression. AB - Erythropoietin (EPO), used to treat anemia in cancer patients, has been reported to accelerate tumor progression and increase mortality. Research of the mechanism for this effect has focused upon EPOR expression by tumor cells. We model the high macrophage to lymphocyte ratio found in tumor microenvironments (TMEs) by culturing peritoneal cavity (PerC) cells that naturally have a high macrophage to T cell ratio. Following TCR ligation, C57BL/6J PerC T cell proliferation is suppressed due to IFNgamma-triggered inducible nitric oxide synthase (iNOS) expression. EPO was tested in the PerC culture model and found to increase T cell suppression. This effect could be abrogated by inhibiting iNOS by enzyme inhibition, genetic ablation, or blocking IFNgamma signaling. Flow cytometry revealed the EPOR on CD11b(+)F4/80(+) macrophages. These results suggest that EPO could increase T cell suppression in the TME by acting directly on macrophages. PMID- 27262377 TI - Insights into anticancer activity and mechanism of action of a ruthenium(II) complex in human esophageal squamous carcinoma EC109 cells. AB - A ruthenium(II) complex [Ru(p-cymene)(NHC)Cl2] (NHC=1,3-bis(4-(tert butyl)benzylimidazol-2-ylidene), referred to as L-4, has been designed and synthesized recently in order to look for new anticancer drugs with high efficacy and low side effects. The anticancer activity and mechanism of action of L-4 in human esophageal squamous carcinoma EC109 cells were systematically investigated. The results revealed that L-4 exerted strong inhibitory effect on the proliferation of EC109 cells, and it arrested EC109 cells at G2/M phase, accompanied with the up-regulation of p53 and p21 and the down-regulation of cyclin D1. The results also showed that the reactive oxygen species (ROS) dependent apoptosis of EC109 can be induced by L-4 via inhibiting the activity of glutathione reductase (GR), decreasing the ratio of glutathione to oxidized glutathione (GSH/GSSG), and leading to the generation of reactive oxygen species. The mitochondria-mediated apoptosis of EC109 induced by L-4 was also observed from the increase of Bax/Bcl-2 ratio, overload of Ca(2+), disruption of mitochondrial membrane potential (MMP), redistribution of cytochrome c, and activation of caspase-3/-9. However, the effects of L-4 on the cell viability, GR activity, GSH/GSSG ratio, reactive oxygen species level, mitochondria dysfunction and apoptosis induction were remarkably attenuated by adding the reactive oxygen species scavenger, NAC. Therefore, it was concluded that L-4 can inhibit the proliferation of EC109 cells via blocking cell cycle progression and inducing reactive oxygen species-dependent and mitochondria-mediated apoptosis. These findings suggested that the ruthenium(II) complex might be a potential effective chemotherapeutic agent for human esophageal squamous carcinoma (ESCC) and worthy of further investigation. PMID- 27262378 TI - Ferulic acid reverses ABCB1-mediated paclitaxel resistance in MDR cell lines. AB - Multidrug resistance (MDR) remains a major obstacle in cancer chemotherapy. The use of the dietary phytochemicals as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention as a plausible approach for overcoming the drug resistance. The aim of this study was to investigate whether a naturally occurring diet-based phenolic acid, ferulic acid, could sensitize paclitaxel efficacy in ABCB1 overexpressing (P glycoprotein) colchicine selected KB Ch(R)8-5 cell line. In vitro drug efflux assays demonstrated that ferulic acid inhibits P-glycoprotein transport function in drug resistant KB Ch(R)8-5 cell lines. However, ferulic acid significantly downregulates ABCB1 expression in a concentration dependent manner. Cytotoxicity assay reveals that ferulic acid decreased paclitaxel resistance in KBCh(R)8-5 and HEK293/ABCB1 cells, which indicates its chemosensitizing potential. Clonogenic cell survival assay and apoptotic morphological staining further confirm the chemosensitizing potential of ferulic acid in drug resistant KB Ch(R)8-5 cell lines. Ferulic acid treatment enhances paclitaxel mediated cell cycle arrest and upregulates paclitaxel-induced apoptotic signaling in KB resistant cells. Hence, it has been concluded that downregulation of ABCB1 and subsequent induction of paclitaxel-mediated cell cycle arrest and apoptotic signaling may be the cause for the chemosensitizing potential of ferulic acid in P-gp overexpressing cell lines. PMID- 27262379 TI - Adalimumab ameliorates OVA-induced airway inflammation in mice: Role of CD4(+) CD25(+) FOXP3(+) regulatory T-cells. AB - Asthma is a chronic inflammatory heterogeneous disorder initiated by a dysregulated immune response which drives disease development in susceptible individuals. Though T helper 2 (TH2) biased responses are usually linked to eosinophilic asthma, other Th cell subsets induce neutrophilic airway inflammation which provokes the most severe asthmatic phenotypes. A growing evidence highlights the role of T regulatory (Treg) cells in damping abnormal Th responses and thus inhibiting allergy and asthma. Therefore, strategies to induce or augment Treg cells hold promise for treatment and prevention of allergic airway inflammation. Recently, the link between Tumor necrosis factor-alpha (TNF alpha) and Treg has been uncovered, and TNF-alpha antagonists are increasingly used in many autoimmune diseases. Yet, their benefits in allergic airway inflammation is not clarified. We investigated the effect of Adalimumab, a TNF alpha antagonist, on Ovalbumin (OVA)-induced allergic airway inflammation in CD1 mice and explored its impact on Treg cells. Our results showed that Adalimumab treatment attenuated the OVA-induced increase in serum IgE, TH2 and TH1 derived inflammatory cytokines (IL-4 and IFN-gamma, respectively) in bronchoalveolar lavage (BAL) fluid, suppressed recruitment of inflammatory cells in BAL fluid and lung, and inhibited BAL fluid neutrophilia. It also ameliorated goblet cell metaplasia and bronchial fibrosis. Splenocytes flow cytometry revealed increased percentage of CD4(+) CD25(+) FOXP3(+) Treg cells by Adalimumab that was associated with increase in their suppressive activity as shown by elevated BAL fluid IL-10. We conclude that the beneficial effects of Adalimumab in this CD1 neutrophilic model of allergic airway inflammation are attributed to augmentation of Treg cell number and activity. PMID- 27262380 TI - Effect of synthetic cannabinoids on spontaneous neuronal activity: Evaluation using Ca(2+) spiking and multi-electrode arrays. AB - Activation of cannabinoid receptor 1 (CB1) inhibits synaptic transmission in hippocampal neurons. The goal of this study was to evaluate the ability of benchmark and emerging synthetic cannabinoids to suppress neuronal activity in vitro using two complementary techniques, Ca(2+) spiking and multi-electrode arrays (MEAs). Neuron culture and fluorescence imaging conditions were extensively optimized to provide maximum sensitivity for detection of suppression of neural activity by cannabinoids. The neuronal Ca(2+) spiking frequency was significantly suppressed within 10min by the prototypic aminoalkylindole cannabinoid, WIN 55,212-2 (10uM). Suppression by WIN 55,212-2 was not improved by pharmacological intervention with signaling pathways known to interfere with CB1 signaling. The naphthoylindole CB1 agonist, JWH-018 suppressed Ca(2+) spiking at a lower concentration (2.5uM), and the CB1 antagonist rimonabant (5uM), reversed this suppression. In the MEA assay, the ability of synthetic CB1 agonists to suppress spontaneous electrical activity of hippocampal neurons was evaluated over 80min sessions. All benchmark (WIN 55,212-2, HU-210, CP 55,940 and JWH-018) and emerging synthetic cannabinoids (XLR-11, JWH-250, 5F-PB-22, AB-PINACA and MAM 2201) suppressed neural activity at a concentration of 10uM; furthermore, several of these compounds also significantly suppressed activity at 1uM concentrations. Rimonabant partially reversed spiking suppression of 5F-PB-22 and, to a lesser extent, of MAM-2201, supporting CB1-mediated involvement, although the inactive WIN 55,212-3 also partially suppressed activity. Taken together, synthetic cannabinoid CB1-mediated suppression of neuronal activity was detected using Ca(2+) spiking and MEAs. PMID- 27262381 TI - Prophylactic acetylsalicylic acid attenuates the inflammatory response but fails to protect exercise-induced liver damage in exercised rats. AB - This study evaluated the effects of acetylsalicylic acid (ASA) on exercise induced inflammatory response, muscle damage, and liver injury in rats. Wistar Kyoto (WKY) rats were divided into six groups: control (C), exercise (E), C+20mg ASA, E+20mg ASA, C+100mg/kg ASA, and E+100mg ASA groups. ASA or a vehicle was orally administered through gavage 1h before a treadmill test. Upon trial completion, blood was drawn at 1, 12, and 24h for biochemical analysis, and livers were excised at 24h for a histological assessment. Our results revealed that 100mg/kg ASA significantly reduced interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha levels in the E groups; however, the IL-10 level was considerably increased. Moreover, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and histological hepatic damage increased significantly in the E+100mg ASA group compared with the corresponding changes in the E group. These results suggest that the prophylactic administration of particularly high-dose ASA alleviates exercise-induced inflammatory response but exacerbates liver injury. PMID- 27262382 TI - SERCA, complex I of the respiratory chain and ATP-synthase inhibition are involved in pleiotropic effects of NS1619 on endothelial cells. AB - A large conductance potassium (BKCa) channel opener, NS1619 (1,3-dihydro-1- [2 hydroxy-5-(trifluoromethyl) phenyl]-5-(trifluoromethyl)-2H-benzimidazole-2-one), is well known for its protective effects against ischemia-reperfusion injury; however, the exact mode of its action remains unclear. The aim of this study was to characterize the effect of NS1619 on endothelial cells. The endothelial cell line EA.hy926, guinea pig hearts and submitochondrial particles isolated from the heart were used. In the isolated guinea pig hearts, which were perfused using the Langendorff technique, NS1619 caused a dose-dependent increase in coronary flow that was inhibited by L-NAME. In EA.hy926 cells, NS1619 also caused a dose dependent increase in the intracellular calcium ion concentration [Ca(2+)]i, as measured using the FURA-2 fluorescent probe. Moreover, NS1619 decreased the oxygen consumption rate in EA.hy926 cells, as assessed using a Clark-type oxygen electrode. However, when NS1619 was applied in the presence of oligomycin, the oxygen consumption increased. NS1619 also decreased the mitochondrial membrane potential, as measured using a JC-1 fluorescent probe in the presence and absence of oligomycin. Additionally, the application of NS1619 to submitochondrial particles inhibited ATP synthase. In summary, NS1619 has pleiotropic actions on EA.hy926 cells and acts not only as an opener of the BKCa channel in EA.hy926 cells but also as an inhibitor of the respiratory chain component, sarcoplasmic reticulum ATPase, which leads to the release of Ca(2+) from the endoplasmic reticulum. Furthermore, NS1619 has the oligomycin-like property of inhibiting mitochondrial ATP synthase. PMID- 27262384 TI - The association among smoking, HSV-1 exposure, and cognitive functioning in schizophrenia, bipolar disorder, and non-psychiatric controls. AB - Previous investigations have found that smokers with schizophrenia demonstrate reduced performance on cognitive tasks compared to non-smokers. However previous studies have not taken into account other environmental factors associated with cognitive functioning such as exposure to Herpes Simplex Virus type 1 (HSV-1). We examined these factors in a sample consisting of individuals with schizophrenia (n=773), bipolar disorder (n=493), or controls without a psychiatric disorders (n=548). Participants were assessed on a cognitive battery, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and had a blood sample drawn to measure seropositivity to HSV-1. Within each group linear regression models were constructed to determine whether cigarette smoking and HSV 1 seropositivity were jointly associated with cognitive functioning after adjusting for relevant covariates. Within the schizophrenia group, the effect size of lower total cognitive score was -0.279 (p<0.0001) for individuals who were both smokers and HSV-1 seropositive and a significant effect was found in all cognitive domains. The odds of being in the highest quartile of RBANS Total score were significantly lower for smokers (OR=0.58, 95% CI 0.41, 0.82, p=0.002). Smoking was not as consistently associated with levels of cognitive functioning in the bipolar disorder or the non-psychiatric control group. While experimental studies show that nicotine transiently improves functioning on sensory gating and attention tasks known to be deficient in schizophrenia, long-term nicotine exposure via smoking appears to have an adverse effect on cognitive functioning. PMID- 27262385 TI - An early intervention for psychosis and its effect on criminal accusations and suicidal behaviour using a matched-cohort design. AB - BACKGROUND: Early interventions for psychosis have been shown to reduce psychotic symptoms and hospital use for first-episode patients, but the effect on suicidal and criminal behaviour has not been reliably determined. This study aimed to examine whether an early intervention for psychosis program (EPPIS) reduced criminal behaviour, suicide attempts, and hospital-based service use. METHODS: The study utilized administrative data to match clients of EPPIS to historical controls. Regression was used to determine the effect of treatment by EPPIS on inpatient use, emergency department use, suicide attempts/deaths, and criminal accusations. RESULTS: A sample of 244 patients was matched to 449 controls. EPPIS patients had lower odds of being accused of a crime both during and after treatment. Suicidal behavior was less frequent among patients, both during treatment (p<0.0001) and after (HR=0.39; 95% CI: 0.17 to 0.94). During treatment there were more emergency department visits for the patients (RR=2.54; 95% CI: 1.56 to 4.58), but no difference in inpatient usage compared to controls. Post treatment, both emergency department and inpatient usage were higher among patients. CONCLUSIONS: EPPIS patients had reduced suicide attempts and criminal accusations. Increased emergency department use could indicate that encouraging treatment during a crisis may increase service use, while reducing suicidal and criminal behaviour. PMID- 27262386 TI - Sleep Ecophysiology: Integrating Neuroscience and Ecology. AB - Here, we propose an original approach to explain one of the great unresolved questions in animal biology: what is the function of sleep? Existing ecological and neurological approaches to this question have become roadblocks to an answer. Ecologists typically treat sleep as a simple behavior, instead of a heterogeneous neurophysiological state, while neuroscientists generally fail to appreciate the critical insights offered by the consideration of ecology and evolutionary history. Redressing these shortfalls requires cross-disciplinary integration. By bringing together aspects of behavioral ecology, evolution, and conservation with neurophysiology, we can achieve a more comprehensive understanding of sleep, including its implications for adaptive waking behavior and fitness. PMID- 27262383 TI - A Systematic Review to Assess Sugar-Sweetened Beverage Interventions for Children and Adolescents across the Socioecological Model. AB - Sugar-sweetened beverage (SSB) consumption among children and adolescents is a determinant of childhood obesity. Many programs to reduce consumption across the socioecological model report significant positive results; however, the generalizability of the results, including whether reporting differences exist among socioecological strategy levels, is unknown. This systematic review aimed to examine the extent to which studies reported internal and external validity indicators defined by the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) model and assess reporting differences by socioecological level: Intrapersonal/interpersonal (Level 1), environmental/policy (Level 2), and multilevel (Combined Level). A systematic literature review was conducted in six major databases (PubMed, Web of Science, Cinahl, CAB Abstracts, Education Research Information Center, and Arcola) to identify studies from 2004-2015 meeting inclusion criteria (children aged 3 to 12 years, adolescents aged 13 to 17 years, and young adults aged 18 years, experimental or quasiexperimental, and substantial SSB component). Interventions were categorized by socioecological level, and data were extracted using a validated RE-AIM protocol. One-way analysis of variance assessed differences between levels. There were 55 eligible studies accepted, including 21 Level 1, 18 Level 2, and 16 Combined Level studies. Thirty-six studies (65%) were conducted in the United States, 19 studies (35%) were conducted internationally, and 39 studies (71%) were implemented in schools. Across levels, reporting averages were low for all RE-AIM dimensions (reach=29%, efficacy or effectiveness=45%, adoption=26%, implementation=27%, and maintenance=14%). Level 2 studies had significantly lower reporting on reach and effectiveness (10% and 26%, respectively) compared with Level 1 (44% and 57%, respectively) or Combined Level studies (31% and 52%, respectively) (P<0.001). Adoption, implementation, and maintenance reporting did not vary among levels. Interventions to reduce SSB consumption in children and adolescents across the socioecological spectrum do not provide the necessary information for dissemination and implementation in community nutrition settings. Future interventions should address both internal and external validity to maximize population influence. PMID- 27262387 TI - The Ecological Role of Sharks on Coral Reefs: Response to Roff et al. PMID- 27262388 TI - Update on the Diagnosis and Management of Familial Long QT Syndrome. AB - This update was reviewed by the CSANZ Continuing Education and Recertification Committee and ratified by the CSANZ board in August 2015. Since the CSANZ 2011 guidelines, adjunctive clinical tests have proven useful in the diagnosis of LQTS and are discussed in this update. Understanding of the diagnostic and risk stratifying role of LQTS genetics is also discussed. At least 14 LQTS genes are now thought to be responsible for the disease. High-risk individuals may have multiple mutations, large gene rearrangements, C-loop mutations in KCNQ1, transmembrane mutations in KCNH2, or have certain gene modifiers present, particularly NOS1AP polymorphisms. In regards to treatment, nadolol is preferred, particularly for long QT type 2, and short acting metoprolol should not be used. Thoracoscopic left cardiac sympathectomy is valuable in those who cannot adhere to beta blocker therapy, particularly in long QT type 1. Indications for ICD therapies have been refined; and a primary indication for ICD in post-pubertal females with long QT type 2 and a very long QT interval is emerging. PMID- 27262389 TI - mHealth in Cardiovascular Health Care. AB - Mobile health (mHealth) has been defined as medical and public health practice supported by mobile devices, such as mobile phones, patient monitoring devices and personal digital assistants. Cardiovascular mHealth is, arguably, leading the mHealth space, through innovation, research and implementation, and especially in the areas of prevention, cardiac rehabilitation and education. mHealth includes simple strategies, such as the use of short message service (SMS) or text messages in successful short-term smoking-cessation, weight loss and diabetes management programs. The recent Australian Tobacco, Exercise and Diet Messages (TEXT ME) randomised clinical trial addressed multiple cardiovascular risk factors. mHealth can also involve more complex strategies, such as smart phone applications (apps), global positioning systems (GPS) and Bluetooth technologies. Although many apps could be considered suitable for primary prevention, they are largely unregulated and most are not evidence-based. Some have been well developed, such as the Food Switch app and an iPhone electrocardiogram (ECG) system. The "explosion" of apps has driven initiatives such as the Mobile Applications Rating Scale (MARS). More recently, the use of sensors to monitor and provide feedback to patients and healthcare providers is being explored. With almost two billion people currently owning a Smartphone, and 50% of adults (globally) predicted to own one by 2018, mHealth provides the prospect of delivering efficient, affordable healthcare services to widespread populations both locally and globally. In particular, it has the potential to reduce socioeconomic disparity and alleviate the burden of cardiovascular disease. There is now a need to rethink traditional health service structures and bioengineering capacity, to ensure mHealth systems are also safe, secure and robust. PMID- 27262390 TI - Qua Vadimus: Heart, Lung and Circulation in 2040. PMID- 27262391 TI - Therapeutic Prospects of Gene Therapy for Atrial Fibrillation. AB - Atrial Fibrillation (AF) is one of the most common types of cardiac arrhythmias experienced in clinical practice, increasing the risk of stroke, dementia, myocardial infarction and death. Currently available options for the treatment of AF use either pharmacological agents or catheter-based ablation therapies to restore sinus rhythm or control the ventricular response rate. These current treatment options are suboptimal at best, motivating research into discovering more effective and innovative ways to treat AF. Gene therapy is being explored for its potential to treat various human conditions including cardiac arrhythmias. Gene transfer vectors with increasing transduction efficiency and biosafety have been developed and trialled for cardiovascular disease treatment. With an improved understanding of the molecular mechanisms of AF, several gene therapy targets have been identified and evaluated in an attempt to rate or rhythm control the heart during AF. This review will discuss the gene therapy vectors in use today and methods for delivery of these vectors to the atrium. Further, it will evaluate several gene therapy strategies and approaches for sinus rhythm restoration and ventricular rate control that have the potential to emerge as a therapy for AF. PMID- 27262392 TI - Television Viewing Time and 13-year Mortality in Adults with Cardiovascular Disease: Data from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). AB - BACKGROUND: In the general population, excessive sedentary behaviour is associated with increased all-cause mortality. Few studies have examined this relationship in people with cardiovascular disease (CVD). Using a sample of people with CVD who were excluded from an analysis of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, we examined the relationship between sedentary behaviour and 13-year all-cause mortality. METHODS: In the original AusDiab study, television viewing time was used as a marker of sedentary behaviour in 609 adults (>=45 years of age) with CVD. During 6,291 person-years of follow-up (median follow-up 13 years), there were 294 deaths (48% of sample). Using the time scale of attained age, the Cox proportional hazards model predicting all-cause mortality adjusted for sex, self-rated general health, leisure-time physical activity, smoking status, education, household income, body mass index, lipid levels, blood pressure, and diabetes mellitus was used. RESULTS: Compared with a TV viewing time of <2hours per day, the fully adjusted hazard ratios for all-cause mortality were 1.18 (95% CI, 0.88 to 1.57) for >=2 to <4hours per day and 1.52 (95% CI, 1.09 to 2.13) for >4hours per day. CONCLUSIONS: Sedentary behaviour was associated with increased risk of all-cause mortality in people with CVD, independent of physical activity and other confounders. In addition to the promotion of regular physical activity, cardiac rehabilitation efforts which also focus on reducing sedentary behaviour may be beneficial. PMID- 27262394 TI - Reply to Re: The Memorial Sloan Kettering Cancer Center Recommendations for Prostate Cancer Screening. PMID- 27262393 TI - Comparison of Percutaneous Renal Mass Biopsy and R.E.N.A.L. Nephrometry Score Nomograms for Determining Benign Vs Malignant Disease and Low-risk Vs High-risk Renal Tumors. AB - OBJECTIVE: To compare the accuracies of renal mass biopsy (RMB) and R.E.N.A.L. nephrometry score (RNS) nomograms for predicting benign vs malignant disease, and low- vs high-risk renal tumors. MATERIALS AND METHODS: We included 281 renal masses in 277 patients who had complete RNS, preoperative RMB, and final pathology from renal surgery for clinically localized renal tumors. RMB and final pathology were determined to be benign or malignant, and malignancies were classified as low-risk (Fuhrman grade I/II) or high-risk (Fuhrman grade III/IV) (benign included in low-risk group). Previously published RNS nomograms were used to determine probabilities of any cancer and high-risk cancer. The gamma statistic was used to assess strength of association between RMB or RNS with final pathology. RESULTS: Of the 281 masses, 13 (5%) and 268 (95%) were confirmed benign and malignant, respectively, and 155 (55%) and 126 (45%) were confirmed low-risk and high-risk, respectively, on final pathology. The areas under the curve of the RNS nomograms for benign vs malignant disease and for low-risk vs high-risk renal tumors were 0.56 and 0.64, respectively. Concordances for predicting benign vs malignant disease were 99% for RMB (P < .01, gamma 0.99) and 29% for RNS nomogram (P = .16, gamma 0.38). Concordances for predicting low-risk vs high-risk renal tumors were 67% for RMB (P < .01, gamma 0.97) and 61% for RNS nomogram (P < .01, gamma 0.47), respectively. CONCLUSION: Although RNS nomograms are useful for discriminating between benign vs malignant renal masses, and low risk vs high-risk renal tumors, they are outperformed by RMB. PMID- 27262395 TI - Differences in Overall and Cancer-specific Survival of Patients Presenting With Chromophobe Versus Clear Cell Renal Cell Carcinoma: A Propensity Score Matched Analysis. AB - OBJECTIVES: To investigate prognostic parameters for the oncological outcome of patients treated for chromophobe renal cell carcinoma (chRCC) in comparison with patients treated for clear cell RCC (ccRCC) using propensity score matching for survival analysis. METHODS: From 1969 to 2009, we identified 1010 from 3567 patients with RCC. Survival was analyzed using Kaplan-Meier estimate for histological subtypes including 109 chRCC and 901 ccRCC. Uni- and multivariate Cox regression was used to analyze prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Propensity score matching was performed to adjust for differences in patient characteristics among histological subgroups. RESULTS: The median follow-up was 61 months (range 0-289). chRCC showed longer OS (5 year, 90.1%; 10 year, 74.2%; 15 year, 61.4%) and CSS (94.2%, 89.7%, 89.7%) compared with ccRCC (OS 75.7%, 54.9%, 46.1% and CSS 84.7%, 75.4%, 72.2%; P = .002). Multivariate Cox regression revealed histology as a significant prognostic factor. Propensity score matching showed a difference in 72.4% (OS) and 87.2% (CSS) of matching attempts confirming the significant impact of histology. Univariate Cox regression showed nephron sparing surgery, no metastasis and no symptoms at presentation, age <65, eosinophilic features, low American Society of Anesthesiologists score, and Charlson Comorbidity Index to be beneficial for CSS. Only age at surgery, metastasis at presentation, and American Society of Anesthesiologists and Charlson Comorbidity Index scores were significant factors for OS in chRCC patients. CONCLUSION: ChRCC appears to have a favorable outcome compared with ccRCC. Even after adjustment for differences in characteristics known to have an influence on survival by propensity score matching, histology remains a significant prognostic factor. PMID- 27262396 TI - Re: Vickers et al: The Memorial Sloan Kettering Cancer Center Recommendations for Prostate Cancer Screening (Urology 2016;91:12-18). PMID- 27262397 TI - [Difficulty in surrogate decision making in spinal muscular atrophy type 1. Author's response]. PMID- 27262398 TI - Integrated chemical and biological assessment of contaminant impacts in selected European coastal and offshore marine areas. AB - This paper reports a full assessment of results from ICON, an international workshop on marine integrated contaminant monitoring, encompassing different matrices (sediment, fish, mussels, gastropods), areas (Iceland, North Sea, Baltic, Wadden Sea, Seine estuary and the western Mediterranean) and endpoints (chemical analyses, biological effects). ICON has demonstrated the use of a framework for integrated contaminant assessment on European coastal and offshore areas. The assessment showed that chemical contamination did not always correspond with biological effects, indicating that both are required. The framework can be used to develop assessments for EU directives. If a 95% target were to be used as a regional indicator of MSFD GES, Iceland and offshore North Sea would achieve the target using the ICON dataset, but inshore North Sea, Baltic and Spanish Mediterranean regions would fail. PMID- 27262399 TI - Effect of water temperature on survival of early-life stages of marbled flounder Pseudopleuronectes yokohamae in Tokyo Bay, Japan. AB - We investigated factors that might have disturbed the stock recovery of marbled flounder in Tokyo Bay by focusing on the early life stages. Field surveys in Tokyo Bay from 2006 to 2011 revealed that mature adult biomass increased from 2006 to 2008 and decreased thereafter. Meanwhile, larval and juvenile densities were high in 2006 and 2008 but low in other years. Discrepancies in the yearly trends of these parameters suggest that mortality during life stages between spawning and early larval phases might have affected the abundance of the subsequent life stages. Monthly mean water temperature between January and February, in which hatching and pelagic larvae occur in the bay, was lower in 2006 (8.6 degrees C) and 2008 (9.6 degrees C) than was observed in other years (10.4-11.4 degrees C). Significant negative correlation between water temperature and larval density implies that mortality during pre- and post-larval stages would be higher in warmer winter years (>10 degrees C). To test this hypothesis, we examined the effects of water temperature on mortality and development in egg and larval stages under controlled laboratory conditions. Hatching rate was high in a water temperature range of 9.2-12.7 degrees C (66.6 82.5%), whereas it decreased in cooler (3.7% at 5.9 degrees C) or warmer (33.9% at 14.8 degrees C) conditions. Meanwhile, days from fertilization to hatching, size of larvae at hatching and survival rate of larvae after 18 d from hatching were monotonically and significantly decreased as water temperature was elevated. Combined evidence of the field and laboratory studies suggests that a warmer reproductive season (>10 degrees C) might induce mortalities of marbled flounder larvae in Tokyo Bay. PMID- 27262400 TI - The origin of renal fibroblasts/myofibroblasts and the signals that trigger fibrosis. AB - Renal fibrosis is a common characteristic of chronic kidney disease (CKD). Aberrant and excessive depositions of extracellular matrix (ECM) proteins in both glomeruli and interstitial regions are typical hallmarks of renal fibrosis and amplify the severity of kidney injury. To date, an approved therapy specifically targeted to renal fibrosis is needed to mitigate or even retard renal fibrosis. Recent findings have identified a unique population of myofibroblasts as a primary source of ECM in scar tissue formation. However, the origin of myofibroblasts in renal fibrosis remains the subject of controversial debates. The advancement in lineage tracing and immunofluorescent microscopy technologies have suggested that myofibroblasts may arise from a number of sources such as activated renal fibroblasts, pericytes, epithelial-to-mesenchymal transition (EMT), endothelial-to-mesenchymal transition (EndoMT), bone marrow derived cells and fibrocytes. Recent studies also indicate that multiple ligands of TGF beta/Smads are the direct mediators for renal fibrosis. Consistently, inhibition of the TGF-beta/Smads signaling pathway using various strategies significantly reduce renal fibrotic lesions and ameliorate kidney injury, suggesting that targeting the TGF-beta/Smads signaling pathway could be a new strategy for effective therapies. In this review, we will briefly discuss the diverse origins of myofibroblasts and molecular pathways triggering renal fibrosis. Prospective therapeutic approaches based on those molecular mechanisms will hopefully offer exciting insights in the development of new therapeutic interventions for patients in the near future. PMID- 27262401 TI - Sox9 overexpression in uterine epithelia induces endometrial gland hyperplasia. AB - SOX9 is a high mobility group transcription factor that is required in many biological processes, including cartilage differentiation, endoderm progenitor maintenance, hair differentiation, and testis determination. SOX9 has also been linked to colorectal, prostate, and lung cancer. We found that SOX9 is expressed in the epithelium of the adult mouse and human uterus, predominantly marking the uterine glands. To determine if SOX9 plays a role in the development of endometrial cancer we overexpressed Sox9 in the uterine epithelium using a progesterone receptor-Cre mouse model. Sox9 overexpression in the uterine epithelium led to the formation of simple and complex cystic glandular structures in the endometrium of aged-females. Histological analysis revealed that these structures appeared morphologically similar to structures present in patients with endometrial hyperplastic lesions and endometrial polyps that are thought to be precursors of endometrial cancer. The molecular mechanisms that cause the glandular epithelium to become hyperplastic, leading to endometrial cancer are still poorly understood. These findings indicate that chronic overexpression of Sox9 in the uterine epithelium can induce the development of endometrial hyperplastic lesions. Thus, SOX9 expression may be a factor in the formation of endometrial cancer. PMID- 27262402 TI - In vitro models for assessing therapeutic angiogenesis. AB - Arterial obstruction leading to ischemia causes a reduction of oxygen and nutrient supply to distal tissues. The physiological response to tissue ischemia triggers a cascade of events that results in the development of accessory vasculature to increase local tissue perfusion and to salvage tissue. However, this adaptive mechanism of repair is suboptimal in some patients. Therapeutic angiogenesis aims to stimulate new blood vessel formation via the local administration of proangiogenic agents or cell therapy products (CTPs). In this review, we provide a summary of the current understanding of in vitro models for assessing the angiogenic potential of a product. PMID- 27262403 TI - Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes. AB - Transglutaminase 2 (TGM2) is a ubiquitously expressed multifunctional protein, which participates in various biological processes including thymocyte apoptosis. As a result, the transcriptional regulation of the gene is complex and must depend on the cell type. Previous studies from our laboratory have shown that in dying thymocytes the expression of Tgm2 is induced by external signals derived from engulfing macrophages, such as retinoids, transforming growth factor (TGF) beta and adenosine, the latter triggering the adenylate cyclase signaling pathway. The existence of TGF-beta and retinoid responsive elements in the promoter region of Tgm2 has already been reported, but the intergenic regulatory elements participating in the regulation of Tgm2 have not yet been identified. Here we used publicly available results from DNase I hypersensitivity analysis followed by deep sequencing and chromatin immunoprecipitation followed by deep sequencing against CCCTC-binding factor (CTCF), H3K4me3, H3K4me1 and H3K27ac to map a putative regulatory element set for Tgm2 in thymocytes. By measuring eRNA expressions of these putative enhancers in retinoid, rTGF-beta or dibutiryl cAMP exposed thymocytes we determined which of them are functional. By applying ChIP qPCR against SMAD4, retinoic acid receptor, retinoid X receptor, cAMP response element binding protein, P300 and H3K27ac under the same conditions, we identified two enhancers of Tgm2, which seem to act as integrators of the TGF beta, retinoid and adenylate cyclase signaling pathways in dying thymocytes. Our study describes a novel strategy to identify and characterize the signal-specific functional enhancer set of a gene by integrating genome-wide datasets and measuring the production of enhancer specific RNA molecules. PMID- 27262404 TI - Lithium toxicity in plants: Reasons, mechanisms and remediation possibilities - A review. AB - Lithium (Li) is a naturally occurring element; however, it is one of the non essential metals for life. Lithium is becoming a serious matter of discussion for the people who do research on trace metals and environmental toxicity in plants. Due to limited information available regarding its mobility from soil to plants, the adverse effects of Li toxicity to plants are still unclear. This article briefly discusses issues around Li, its role and its essentiality in plants and research directions that may assist in inter-disciplinary studies to evaluate the importance of Li's toxicity. Further, potential remediation approaches will also be highlighted in this review. Briefly, Li influenced the growth of plants in both stimulation and reduction ways, depending on the concentration of Li in growth medium. On the negative side, Li reduces the plant growth by interrupting numerous physiological processes and altering metabolism in plant. The contamination of soil by Li is becoming a serious problem, which might be a threat for crop production in the near future. Additionally, lack of considerable information about the tolerance mechanisms of plants further intensifies the situation. Therefore, future research should emphasize in finding prominent and approachable solutions to minimize the entry of Li from its sources (especially from Li batteries) into the soil and food chain. PMID- 27262405 TI - Photosynthetic adaptation strategy of Ulva prolifera floating on the sea surface to environmental changes. AB - For 8 consecutive years, a green tide has originated in the southern Yellow Sea and spread to the Qingdao offshore area. The causative species, Ulva prolifera, always forms a very thick thallus mat that is capable of drifting long distances over long periods. During this process, although the thalli face disturbance by complex environmental factors, they maintain high biomass and proliferation. We hypothesized that some form of photosynthetic adaptation strategy must exist to protect the thalli. Therefore, we studied the different photosynthetic response characteristics of the surface and lower layers of the floating thallus mats, and investigated the physiological and molecular-level adaptation mechanisms. The results showed that: (1) U. prolifera has strong photosynthetic capability that ensures it can gain sufficient energy to increase its biomass and adapt to long distance migration. (2) Surface layer thalli adapt to the complex environment by dissipating excess energy via photosynthetic quantum control (energy quenching and energy redistribution between PSII/PSI) to avoid irreversible damage to the photosynthetic system. (3) Lower layer thalli increase their contents of Chlorophyll a (Chl a) and Chlorophyll b (Chl b) and decrease their Chl a/Chl b ratio to improve their ability to use light energy. (4) U. prolifera has strong photosynthetic plasticity and can adapt to frequent exchange between the surface and lower layer environments because of wave disturbance. Pigment component changes, energy quenching, and energy redistribution between PSII/PSI contribute to this photosynthetic plasticity. PMID- 27262407 TI - Three-dimensional evaluation of heel raise test in pediatric planovalgus feet and normal feet. AB - Planovalgus foot is a common pediatric deformity which may be associated with pain. To evaluate flexibility of the foot, the heel raise test is used. During this test the arch and hindfoot are assessed. Several studies have described planovalgus foot based on 3D gait and standing analysis. However, no studies have evaluated foot flexibility during heel raise using an objective 3D analysis. Therefore, the purpose of this study is to evaluate the flexibility of planovalgus feet during the heel raise test using an objective 3D assessment and to determine whether any hypotheses can be generated about potential differences between painful and painless flexible planovalgus feet and reference feet. Here, 3D foot analysis was conducted in 33 children (7 reference feet, 16 painless, and 10 painful flexible planovalgus feet) during the heel raise test. To identify the characteristics of planovalgus foot, the concept of 3D projection angles was used as introduced in the Heidelberg Foot Measurement Method (HFMM), with a modified marker set. All feet showed dynamic movements of the medial arch and hindfoot from valgus to varus position during heel raise. Reference feet had the smallest range of motion, perhaps due to joint stability and absence of foot deformity. Painful and painless flexible planovalgus feet demonstrated similar movements. No significant differences were found between the painful and painless groups. However, the kinematics of the pain group seemed to differ more from those of the reference group than did kinematics of the painless group. This assessment is a new, practical, and objective method to measure the flexibility of small children's feet. PMID- 27262406 TI - From tamoxifen to dendrogenin A: The discovery of a mammalian tumor suppressor and cholesterol metabolite. AB - Tamoxifen (Tam) was developed as a ligand and modulator of estrogen receptor alpha (ERalpha) and is one of the main drugs used globally for the hormonotherapy of breast cancers. Besides ERalpha, Tam also binds with high affinity to the microsomal antiestrogen binding site (AEBS). The AEBS is a hetero-oligomeric proteinaceous complex with cholesterol-5,6-epoxide hydrolase (ChEH) activity that is associated with an intracellular histamine (HA) binding site. The enzymatic activities of the ChEH subunits control developmental programs in mammals and transform cholesterol-5,6-epoxides (5,6-EC) into cholestane-3beta,5alpha,6beta triol. Inhibition of the ChEH activity by pharmacological agents such as Tam induce cancer cell re-differentiation through the accumulation of 5,6-EC. A few years ago, the putative chemical reactivity of the 5,6-EC epoxide group towards nucleophiles led our group to hypothesize that 5,6-EC could react with HA that was co-localized at the AEBS to give a new molecule involved in cell differentiation. This hypothesis was chemically tested and the conjugation of 5,6alpha-EC: with HA was found possible but only under catalytic conditions. It gave a stereo-selective single product of transformation which was named dendrogenin A (DDA). DDA was found to display potent cancer cell differentiation and anticancer properties in vitro and in vivo, suggesting that it was a tumor suppressor metabolite. The presence of DDA was then established in several mammalian tissues, providing the first evidence of a steroidal alkaloid metabolite in mammals. The discovery of DDA highlights a new metabolic pathway in mammals which lies at the crossroads of cholesterol and histamine metabolism and produces this tumor suppressor metabolite. PMID- 27262408 TI - A new semisynthetic 1-O-acetyl-6-O-lauroylbritannilactone induces apoptosis of human laryngocarcinoma cells through p53-dependent pathway. AB - Initiation of apoptosis is an important event for chemoprevention and chemotherapy of cancer. Naturally derived products had drawn growing attention as lead compounds for anticancer drug discovery. ABL-L, a semisynthetic analogue of natural sesquiterpenoid 1-O-acetylbritannilactone (ABL) isolated from Inula britannica, showed stronger suppression against three solid tumor cell lines with 4-10 fold improvement than ABL. However, its molecular mechanism of cell death induction has still not been determined. The present study evaluated the anticancer efficacy of ABL-L and its biological activities mechanism on human laryngocarcinoma cells HEp-2 in vitro. We found that ABL-L-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest. Typical apoptotic morphological and biochemical features were also observed in treated cells. Furthermore, the levels of the anti-apoptotic Bcl-2, pro-caspase 3/8/9 and poly(ADP-ribose) polymerase PARP decreased, and the level of pro-apoptotic Bax increased. Involvement of the caspase-mediated apoptosis was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. In addition, ABL-L induced a tumor suppressor p53 and its target genes expression p21, fas, noxa and puma. The results of p53 knockdown suggest that caspase-mediated apoptosis induced by ABL-L was in p53-dependent pathway on HEp-2 cells. Our data indicate that the cytotoxicity of the novel semisynthetic analogue ABL-L involved G1 cell cycle arrest and apoptosis via a p53-dependent, caspase-mediated pathway on human laryngocarcinoma cells. PMID- 27262409 TI - Grade of coracoacromial ligament degeneration as a predictive factor for impingement syndrome and type of partial rotator cuff tear. AB - BACKGROUND: The purpose of this study was to investigate the role of coracoacromial ligament degeneration and specific anatomic parameters in the etiology of partial-thickness rotator cuff tears. MATERIALS AND METHODS: This study retrospectively assessed 96 patients (mean age, 50.1 years [17-76]; 34 men, 62 women) diagnosed with bursal-side and articular-side rotator cuff tears with a history of failed conservative treatment and persistent shoulder pain who underwent arthroscopic surgery. Video records of the surgery were used to evaluate the type of cuff tear, grade of coracoacromial ligament degeneration, and associated pathologic changes; preoperative magnetic resonance images were used to measure acromioglenoid angle, supraspinatus glenoid angle, and subacromial distance. RESULTS: Most of the patients with articular-side tears demonstrated grade 0 and grade 1 coracoacromial ligament degeneration, whereas patients with bursal-side tears had grade 1 and grade 2. There was a significant positive correlation between the grade of coracoacromial ligament degeneration and bursal-side partial rotator cuff tears, whereas no correlation was observed with articular-side tears. There was no significant difference between bursal side and articular-side partial cuff tears regarding acromioglenoid angle, supraspinatus glenoid angle, and subacromial distance. CONCLUSIONS: Grade 1 and grade 2 coracoacromial ligament degeneration is a strong predictive factor for impingement syndrome in the etiology of bursal-side partial cuff tears and can guide the surgeon to consider ligament release and debridement or acromioplasty in these patients. PMID- 27262411 TI - Reproducibility of isometric shoulder protraction and retraction strength measurements in normal subjects and individuals with winged scapula. AB - BACKGROUND: The strength of the shoulder protractors and retractors may be compromised in individuals with winged scapula (IwWS). However, no standard approach to measuring the strength of these muscles has been described. The aim of this study was to study the intra-rater and inter-rater reproducibility of a fixed-base isometric dynamometer and to describe cutoff scores for clinically meaningful change for protraction and retraction isometric strength. METHOD: Twice during a week, 20 normal subjects and 20 IwWS were tested by 2 independent raters. RESULTS: IwWS were significantly weaker (P < .001) than control subjects in their protraction and retraction isometric strength. Excellent intra-rater and inter-rater correlations were obtained in most combinations, leading to low cutoff scores for meaningful change expressed in terms of the smallest real difference. CONCLUSION: When it is properly used, the technique described in this paper is recommended as an effective clinical tool for the quantitative assessment of protraction and retraction isometric strength, both for status determination and for monitoring of change in IwWS during and after rehabilitation. PMID- 27262410 TI - Impaction autografting: bone-preserving, secure fixation of a standard humeral component. AB - BACKGROUND: When fixed with bone ingrowth, a tight diaphyseal press fit, or cement, the humeral component of a shoulder arthroplasty may present problems of malposition, stress shielding, or periprosthetic fracture or difficulty with removal at revision arthroplasty. We have avoided the need for these fixation methods by using impaction cancellous autografting of the humeral stem, minimizing contact between the prosthetic stem and the humeral cortex. This study presents the radiographic survivorship of impaction-autografted humeral implants using component subsidence as the primary endpoint. METHODS: We reviewed 286 primary anatomic shoulder arthroplasties having an average follow-up of 4.9 +/- 2.7 years. Initial postoperative radiographs and minimum 2-year follow-up radiographs were evaluated by 3 observers to assess subsidence. RESULTS: Two different implants (Humeral Replacement Prosthesis [HRP] and Global Advantage prosthesis) were used. Of 286 stems, 267 (93.4%) had not subsided. The Global Advantage prosthesis had a subsidence-free survival rate of 98.5% at 5 years. The stiffer-stemmed HRP used early during the study had a higher rate of subsidence compared with the currently used Global Advantage stem (hazard ratio, 5.6; P = .001). Radiolucent lines of 2 mm or greater were less common for the Global Advantage prosthesis than for the HRP in each of 7 zones (P < .001). Total shoulder arthroplasty was associated with a higher rate of subsidence compared with hemiarthroplasty (hazard ratio, 2.6; P = .12). CONCLUSIONS: Impaction autografting provides a secure, durable, bone-preserving means of humeral component fixation in anatomic shoulder arthroplasty. PMID- 27262412 TI - Does application of moderately concentrated platelet-rich plasma improve clinical and structural outcome after arthroscopic repair of medium-sized to large rotator cuff tear? A randomized controlled trial. AB - BACKGROUND: Platelet-rich plasma (PRP) has the potential to improve tendon-bone healing. The evidence is still controversial as to whether PRP application after repair of medium-sized to large cuff tears leads to superior structural and clinical outcome, especially after single-row repair. METHODS: In a randomized study, 102 patients (PRP group, 52 patients; control group, 50 patients) with medium-sized and large degenerative posterosuperior tears were included for arthroscopic repair with a minimum follow-up of 2 years. Patients were evaluated with clinical scores (visual analog scale score, Constant-Murley score, University of California-Los Angeles score, and American Shoulder and Elbow Surgeons score) and ultrasound to assess retear and vascularity pattern of the cuff. RESULTS: Visual analog scale scores were significantly lower in the PRP group than in controls at 1 month, 3 months, and 6 months but not later. Constant Murley scores were significantly better in the PRP group compared with controls at 12 and 24 months, whereas University of California-Los Angeles scores were significantly higher in the PRP group at 6 and 12 months (P < .05). The American Shoulder and Elbow Surgeons score in both groups was comparable at all the times. At 24 months, retear in the PRP group (n = 2; 3.8%) was significantly lower than in the control group (n = 10; 20%; P = .01). The retear difference was significant only for large tears (PRP:control group, 1:6; P = .03). Doppler ultrasound examination showed significant vascularity in the PRP group repair site at 3 months postoperatively (P < .05) and in peribursal tissue until 12 months. CONCLUSION: Application of moderately concentrated PRP improves clinical and structural outcome in large cuff tears. PRP also enhances vascularity around the repair site in the early phase. PMID- 27262413 TI - Tobacco use is associated with increased rates of infection and revision surgery after primary superior labrum anterior and posterior repair. AB - BACKGROUND: Although the general health consequences of tobacco use have been well defined, the effects of perioperative tobacco use on arthroscopic shoulder procedures remain largely unknown. The purpose of this study is to use a national database to investigate the relationship between tobacco use and rates of superior labrum anterior and posterior (SLAP) repair failure and postoperative infection after primary SLAP repair compared with matched controls. METHODS: A national private-payer insurance database was queried for patients who underwent arthroscopic primary SLAP from 2005-2012. These patients were divided into tobacco use and non-tobacco use cohorts using International Classification of Diseases, Ninth Revision coding. The non-tobacco use patients were then matched to the patients with coded tobacco use. Both cohorts were assessed for postoperative infection within 90 days and subsequent ipsilateral revision SLAP repair or biceps tenodesis within up to 7 years postoperatively. RESULTS: The incidences of revision SLAP repair or revision to a biceps tenodesis (P = .023) and postoperative infection (P = .034) were significantly higher in patients who used tobacco versus matched controls. CONCLUSIONS: SLAP repair in patients who use tobacco is associated with significantly increased rates of postoperative infection and revision SLAP repair or conversion to a biceps tenodesis. PMID- 27262414 TI - Relationship between the water-exchangeable fraction of PAH and the organic matter composition of sediments. AB - The sorption of PAH on 12 different sediments was investigated and was correlated to their corresponding organic matter (OM) content and quality. For this purpose, the OM was precisely characterized using thermal analysis consisting in the successive combustion and quantification of the increasingly thermostable fractions of the OM. Simultaneously, the water-exchangeable fraction of the sorbed PAH defined as the amount of PAH freely exchanged between the water and the sediment (by opposition to the PAH harshly sorbed to the sediments particles) was determined using a passive sampler methodology recently developed. The water concentrations, when the sediment-water system is equilibrated, were also assessed which allows the determination of the sediment-water distribution coefficients without artifacts introduced by the non water-exchangeable fraction of PAH. Hence, the present study provides the distribution coefficients of PAH between the water and 4 different OM fractions combusted at a specific temperature range. The calculated distribution coefficients demonstrate that the sedimentary OM combusted at the intermediate temperature range (between 300 degrees C and 450 degrees C) drives the reversible sorption of PAH while the inferred sorption to the OM combusted at a lower and higher temperature range does not dominate the partitioning process. PMID- 27262415 TI - On the importance of modelling the internal spatial dynamics of biological cells. AB - Spatial effects such as cell shape have very often been considered negligible in models of cellular pathways, and many existing simulation infrastructures do not take such effects into consideration. Recent experimental results are reversing this judgement by showing that very small spatial variations can make a big difference in the fate of a cell. This is particularly the case when considering eukaryotic cells, which have a complex physical structure and many subtle control mechanisms, but bacteria are also interesting for the huge variation in shape both between species and in different phases of their lifecycle. In this work we perform simulations that measure the effect of three common bacterial shapes on the behaviour of model cellular pathways. To perform these experiments we develop ReDi-Cell, a highly scalable GPGPU cell simulation infrastructure for the modelling of cellular pathways in spatially detailed environments. ReDi-Cell is validated against known-good simulations, prior to its use in new work. We then use ReDi-Cell to conduct novel experiments that demonstrate the effect that three common bacterial shapes (Cocci, Bacilli and Spirilli) have on the behaviour of model cellular pathways. Pathway wavefront shape, pathway concentration gradients, and chemical species distribution are measured in the three different shapes. We also quantify the impact of internal cellular clutter on the same pathways. Through this work we show that variations in the shape or configuration of these common cell shapes alter model cell behaviour. PMID- 27262416 TI - The acoustic communities: Definition, description and ecological role. AB - An acoustic community is defined as an aggregation of species that produces sound by using internal or extra-body sound-producing tools. Such communities occur in aquatic (freshwater and marine) and terrestrial environments. An acoustic community is the biophonic component of a soundtope and is characterized by its acoustic signature, which results from the distribution of sonic information associated with signal amplitude and frequency. Distinct acoustic communities can be described according to habitat, the frequency range of the acoustic signals, and the time of day or the season. Near and far fields can be identified empirically, thus the acoustic community can be used as a proxy for biodiversity richness. The importance of ecoacoustic research is rapidly growing due to the increasing awareness of the intrusion of anthropogenic sounds (technophonies) into natural and human-modified ecosystems and the urgent need to adopt more efficient predictive tools to compensate for the effects of climate change. The concept of an acoustic community provides an operational scale for a non intrusive biodiversity survey and analysis that can be carried out using new passive audio recording technology, coupled with methods of vast data processing and storage. PMID- 27262417 TI - Malaria vaccines and human immune responses. AB - Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. PMID- 27262418 TI - Isolated pure verbal amnesia as the disease onset of probable multiple sclerosis with a left forniceal black hole. PMID- 27262420 TI - Quantifying and Predicting Surgeon Work Effort for Primary and Revision Total Knee Arthroplasty. AB - BACKGROUND: The objectives of this study were to quantify increased utilization of resources in revision total knee arthroplasty (TKA) compared with primary TKA, determine preoperative factors that predict outcome measures, and compare Medicare reimbursement for each procedure. METHODS: Seventy-eight revision TKA patients were compared with 80 primary TKA patients. Outcomes measured were surgical time, estimated blood loss, length of stay, and complications. RESULTS: Revision TKA showed 49% increased surgical time compared with primary TKA. Estimated blood loss was increased 91%. Tibial and femoral bone loss was associated with increased surgical time as was use of longer stemmed tibial components. Average Medicare hospital payment increased 29% ($13,464 for primary, $17,331 for revision). Average physician reimbursement represented a 36% increase. Relative value units were increased to 31%. CONCLUSION: There was substantial increase in work effort not commensurate with current Medicare reimbursement, which may limit patient access to revision TKA. PMID- 27262419 TI - Multiple Boluses of Intravenous Tranexamic Acid to Reduce Hidden Blood Loss After Primary Total Knee Arthroplasty Without Tourniquet: A Randomized Clinical Trial. AB - BACKGROUND: The optimal dosage and timing of tranexamic acid (TXA) in total knee arthroplasty (TKA) are undetermined. The purpose of this study was to explore the effect of multiple boluses of intravenous TXA on hidden blood loss (HBL), inflammatory response, and knee function after primary TKA without tourniquet. METHODS: A total of 151 patients were randomly divided into 3 groups to receive single bolus of 20 mg/kg IV-TXA before skin incision (group A), or another bolus of 10 mg/kg IV-TXA 3 hours later (group B), or another 2 boluses of 10 mg/kg IV TXA 3 hours and 6 hours later (group C). TKAs without tourniquet were operated by 1 single surgeon. The primary outcomes were HBL and maximum hemoglobin drop. Other outcome measurements such as total blood loss, transfusion rate, inflammation markers (C-reactive protein, interleukin 6), visual analog scale pain score, limb swelling ratio, Hospital for Surgery Score, range of motion, length of hospital stay (LOH), and deep venous thrombosis were also compared. RESULTS: The mean HBL and maximum Hb drop in group C (467.6 +/- 305.9 and 20.9 +/ 9.3) was lower than those in group A (763.0 +/- 373.3, P < .001; 28.7 +/- 12.2, P < .001) and group B (637.5 +/- 303.5, P = .010; 25.2 +/- 8.4, P = .036). However, such differences were not detected between groups A and B (P = .058 and P = .080, respectively). The mean value of total blood loss in the groups A, B, and C were 967.2 +/- 380.1, 803.7 +/- 321.8, and 677.6 +/- 326.0 mL, respectively, with a significant intergroup difference (P < .001). The mean serum level of C-reactive protein and interleukin 6 in group C were lower than those in group A and group B on postoperative days 1 and 2. The visual analog scale pain score and swelling ratio were also lower in group C than in the other 2 groups with statistical significance on POD 1-3. Moreover, the Hospital for Surgery Score, range of motion, and LOH were better in group C. No episodes of transfusion or deep venous thrombosis had occurred. CONCLUSION: Multiple boluses of IV-TXA can effectively reduce HBL after primary TKA without tourniquet. What is the most important is that, by adding another bolus of IV-TXA, patients can gain a smaller decline of Hb, less postoperative inflammatory response, less pain, less knee swelling, better knee function, and shorter LOH. PMID- 27262421 TI - "How do I feel today?" An Analysis of HRQOL Variability among Institutionalized Older Adults. AB - Intra-individual variability is a central topic in Nonlinear Dynamical Systems (NDS) studies of human development, because the theory predicts that particular forms or properties of intra-individual variability will serve as indicators or predictors of bifurcations, and stable states in individual development. Currently, there are almost no studies that address intra-individual changes and variability of Health Related Quality of Life in old age. The main aim of this paper is to analyze the role of day-to-day HRQOL variability and long term HRQOL and disability development in a sample of institutionalized older adults. 22 older adults took part in this longitudinal study. Daily diary-based assessments were made for a period of 100 days. Furthermore, monthly assessments of HRQOL and disability with validated questionnaires were performed. The intra individual variability on a day-to-day basis was found to be related to HRQOL and disability development. Furthermore, life events as operationalized by extreme values in HRQOL were related to the level of day-to-day HRQOL variability. As predicted by NDS theory, day-to-day variability emerges as an important indicator of levels of and changes in HRQOL and disability and as such, it may be an important indicator of developmental processes in old age. PMID- 27262422 TI - Combination of sLORETA and Nonlinear Coupling for Emotional EEG Source Localization. AB - The objective of the present study is to investigate the anatomical distribution of the cortical sources of emotional response to music videos by means of electroencephalogram (EEG) analysis. A novel methodology is introduced to determine the nonlinear couplings between different brain regions based on the coherence analysis, nonlinear features of EEG recordings and a source localization method, standard low resolution electromagnetic tomography (sLORETA). 32 channels of EEG time series of 32 subjects available in DEAP database were studied. The Lyapunov exponents and approximate entropy were applied to the EEG. The coherence for Lyapunov exponents and approximate entropy were calculated between each electrode paired to all other electrodes. Considering valence and arousal related effects, the sLORETA was applied to each above mentioned feature to determine emotional processing cortices. Using the proposed methodology, significant differences in sLORETA activity are observed between different emotional states. These changes were dominantly localized in the Brodmann 11 area (frontal lobe). In addition, some evidences provided that the left hemisphere is more activated to valence and arousal-related effects. Results suggest that considering two dimensions of emotions concurrently, a wider brain region was dominated in synchronization: superior frontal gyrus, middle frontal gyrus, and superior parietal lobule. Cooperating nonlinear coupling along with EEG source localization methods could provide an interesting tool for understanding the cortical specialization in emotional processes. PMID- 27262423 TI - The Mathematics of Psychotherapy: A Nonlinear Model of Change Dynamics. AB - Psychotherapy is a dynamic process produced by a complex system of interacting variables. Even though there are qualitative models of such systems the link between structure and function, between network and network dynamics is still missing. The aim of this study is to realize these links. The proposed model is composed of five state variables (P: problem severity, S: success and therapeutic progress, M: motivation to change, E: emotions, I: insight and new perspectives) interconnected by 16 functions. The shape of each function is modified by four parameters (a: capability to form a trustful working alliance, c: mentalization and emotion regulation, r: behavioral resources and skills, m: self-efficacy and reward expectation). Psychologically, the parameters play the role of competencies or traits, which translate into the concept of control parameters in synergetics. The qualitative model was transferred into five coupled, deterministic, nonlinear difference equations generating the dynamics of each variable as a function of other variables. The mathematical model is able to reproduce important features of psychotherapy processes. Examples of parameter dependent bifurcation diagrams are given. Beyond the illustrated similarities between simulated and empirical dynamics, the model has to be further developed, systematically tested by simulated experiments, and compared to empirical data. PMID- 27262424 TI - Addressing the Policy Churn in Public Education in the United States. AB - Educational organizations, public schools in particular, are seen as being notoriously inert and resistant to change. While school reform efforts are widespread, educational outcomes such as high school graduation rates and achievement in reading and math continue to show disparity between socio-economic groups. Why is educational change so hard to accomplish? This article approaches the question from two perspectives: the school reform literature that identifies the factors inhibiting change in school systems, and the literature on complex dynamical systems (CDS), which facilitates understanding of the dynamics underlying inertia and transformation. The need is articulated for empirical research that focuses on reform as an implementation process, to provide further insight in what we know about its impact on educational outcomes. PMID- 27262425 TI - Structure-activity relationships of dibenzoylhydrazines for the inhibition of P glycoprotein-mediated quinidine transport. AB - We previously demonstrated that dibenzoylhydrazines (DBHs) are not only P glycoprotein (P-gp) substrates, but also inhibitors. In the present study, we evaluated the inhibition of P-gp-mediated quinidine transport by two series of DBHs and performed a classical QSAR analysis and docking simulation in order to investigate the mechanisms underlying P-gp substrate/inhibitor recognition. The results of the QSAR analysis identified the hydrophobic factor as the most important for inhibitory activities, while electronic and steric effects also influenced the activities. The different substituent effects observed in each series suggested the different binding modes of each series of DBHs, which was supported by the results of the docking simulation. PMID- 27262426 TI - New bifunctional antioxidant/sigma1 agonist ligands: Preliminary chemico-physical and biological evaluation. AB - We previously reported bifunctional sigma-1 (sigma1) ligands endowed with antioxidant activity (1 and 2). In the present paper, pure enantiomers (R)-1 and (R)-2 along with the corresponding p-methoxy (6, 11), p-fluoro derivatives (7, 12) were synthesized. sigma1 and sigma2 affinities, antioxidant properties, and chemico-physical profiles were evaluated. Para derivatives, while maintaining strong sigma1 affinity, displayed improved sigma1 selectivity compared to the parent compounds 1 and 2. In vivo evaluation of compounds 1, 2, (R)-1, 7, and 12 showed sigma1 agonist pharmacological profile. Chemico-physical studies revealed that amides 2, 11 and 12 were more stable than corresponding esters 1, 6 and 7 under our experimental conditions. Antioxidant properties were exhibited by fluoro derivatives 7 and 12 being able to increase total antioxidant capacity (TAC). Our results underline that p-substituents have an important role on sigma1 selectivity, TAC, chemical and enzymatic stabilities. In particular, our data suggest that new very selective compounds 7 and 12 could be promising tools to investigate the disorders in which sigma1 receptor dysfunction and oxidative stress are contemporarily involved. PMID- 27262427 TI - Inhibiting DNA methylation alters olfactory extinction but not acquisition learning in Apis cerana and Apis mellifera. AB - DNA methylation plays a key role in invertebrate acquisition and extinction memory. Honey bees have excellent olfactory learning, but the role of DNA methylation in memory formation has, to date, only been studied in Apis mellifera. We inhibited DNA methylation by inhibiting DNA methyltransferase (DNMT) with zebularine (zeb) and studied the resulting effects upon olfactory acquisition and extinction memory in two honey bee species, Apis cerana and A. mellifera. We used the proboscis extension reflex (PER) assay to measure memory. We provide the first demonstration that DNA methylation is also important in the olfactory extinction learning of A. cerana. DNMT did not reduce acquisition learning in either species. However, zeb bidirectionally and differentially altered extinction learning in both species. In particular, zeb provided 1h before acquisition learning improved extinction memory retention in A. mellifera, but reduced extinction memory retention in A. cerana. The reasons for these differences are unclear, but provide a basis for future studies to explore species-specific differences in the effects of methylation on memory formation. PMID- 27262428 TI - Molecular phylogenetics of the Neotropical fish family Prochilodontidae (Teleostei: Characiformes). AB - Migratory detritivores of the characiform family Prochilodontidae occur throughout the freshwaters of much of South America. Prochilodontids often form massive populations and many species achieve substantial body sizes; a combination that makes them one of the most commercially important fish groups on the continent. Their economic significance notwithstanding, prochilodontids have never been the subject of a comprehensive molecular phylogenetic analysis. Using three mitochondrial and three nuclear loci spanning all prochilodontid species, we generated a novel phylogenetic hypothesis for the family. Our results strongly support monophyly of the family and the three included genera. A novel, highly supported placement of Ichthyoelephas sister to the clade containing Prochilodus and Semaprochilodus diverges from a previous morphological hypothesis. Most previously hypothesized interspecific relationships are corroborated and some longstanding polytomies within Prochilodus and Semaprochilodus are resolved. The morphologically similar P. brevis, P. lacustris, P. nigricans and P. rubrotaeniatus are embedded within what is herein designated as the P. nigricans group. Species limits and distributions of these species are problematic and the group clearly merits taxonomic revision. PMID- 27262429 TI - The use of statistical methods for censored data to evaluate the activity concentration of Pb-210 in beans (Phaseolus vulgaris L.). AB - A survey of 210Pb activity concentration, one of the major internal natural radiation sources to man, has been carried in the most common species of beans (Phaseolus vulgaris L.) grown and consumed in Brazil. The representative bean types chosen, Carioca beans and black type sown in the Brazilian Midwestern and Southern regions, have been collected in this study and 210Pb determined by liquid scintillation spectrometry after separation with chromatographic extraction using Sr-resin. Available values in data set of radioactivity in Brazil (GEORAD) on the 210Pb activity concentration in black beans grown in Southeastern region have been added to the results of this study with the purpose of to amplify the population considered. Concerning the multiple detection limits and due to the high level of censored observations, a robust semi-parametric statistical method called regression on order statistics (ROS) has been employed to provide a reference value of the 210Pb in Brazilian beans, which amounted to 41 mBq kg-1 fresh wt. The results suggest that the 210Pb activity concentration in carioca beans is lower than in black beans. Also evaluated was the 210Pb activity concentration in vegetable component of a typical diet, which displays lower values than those shown in the literature for food consumed in Europe. PMID- 27262430 TI - Chemical distribution of hazardous natural radionuclides during monazite mineral processing. AB - It is very important to calculate the radioactivity concentration for low-grade monazite ore (50%) and different other materials produced as results of chemical processing stages to avoid the risk to workers. Chemical processing of low-grade monazite pass through different stages, washing by hydrochloric acid and digested with sulfuric acid and influence of pH on the precipitation of rare earth elements has been studied. The radioactivity concentrations of 238U(226Ra) and 232Th as well as 40K were calculated in crude low-grade ore and found to be 54,435 +/- 3138, 442,105 +/- 29,200 and 5841 +/- 345 Bq/kg, respectively. These values are greatly higher than the exempt levels 25 Bq/kg. After chemical digestion of the ore, the results demonstrated that un-reacted material contains significant radioactivity reached to approximately 8, 13 and 23% for 238U, 232Th and 40K, respectively. The results show that 60% of 232Th are located in the digested white slurry with small portions of 238U and 40K. Most of 238U radioactivity is extracted in the green phosphoric acid which produced from conversion of P2O5 by H2SO4 into phosphoric acid. The average values of the Raeq for monazite ore, un-reacted black precipitate, white precipitate, brown precipitate and crystalline material samples were calculated and found to be 687,095 +/- 44,921, 85,068 +/- 5339, 388,381 +/- 22,088, 313,046 +/- 17,923 and 4531 +/- 338 Bq/kg, respectively. The calculated values of Raeq are higher than the average world value (it must be less than 370 Bq/kg). Finally the external hazardous, internal hazardous and Igammar must be less than unity. This means that specific radiation protection program must be applied and implemented during monazite processing. PMID- 27262432 TI - A State Transition Model for Health Outcomes Associated with Vorapaxar Treatment as an Add-on to Standard Care Antiplatelet Therapy in the Prevention of Thrombotic Events for Patients with a Recent Myocardial Infarction. AB - BACKGROUND: The TRA 2 degrees P-TIMI 50 trial showed the addition of vorapaxar to standard care (SC) antiplatelet therapy reduced the combined risk of death, myocardial infarction (MI), and stroke, while exhibiting an increase in moderate, but not other bleeding events. OBJECTIVE: Our objective was to estimate the long term health benefits and risks of vorapaxar as an add-on to SC treatment (lifetime aspirin and up to 12 months of clopidogrel) for patients with a prior MI and without a history of cerebrovascular disease. METHODS: In the state transition model we developed, the patients transition between states due to recurrent MI, stroke, or death, and are at risk of non-fatal bleeding. Risk equations were developed from individual patient-level data from the TRA 2 degrees P-TIMI 50 trial to predict long-term cardiovascular (CV) outcomes. Additional sources informed inputs for case fatality, bleeding rates on SC, risk of non-CV death, and utilities. RESULTS: Over a lifetime horizon, fewer CV events and more bleeding events occurred in the vorapaxar (VOR) + SC arm, relative to the SC-only arm. These results were ultimately accompanied by an increase in life expectancy and health benefits associated with add-on vorapaxar treatment, as the VOR + SC arm yielded an average of 8.27 discounted quality-adjusted life-years (QALYs) compared with an average of 7.96 discounted QALYs in the SC-only arm. CONCLUSION: This model framework leveraged novel risk equations to make long-term projections of CV events in a population at high risk of recurrence. Model results suggest vorapaxar is most effective as add-on therapy to SC antiplatelet treatment when initiated upon hospital discharge post-MI. PMID- 27262433 TI - A Summary of the Literature Evaluating Adherence and Persistence with Oral Anticoagulants in Atrial Fibrillation. AB - Atrial fibrillation (AF) is a growing public health concern and remains an independent risk factor for ischemic stroke. Warfarin, a commonly used oral anticoagulant, is associated with a 60-70 % relative reduction in stroke risk and a reduction in mortality of 26 %. However, warfarin has several limitations, including a narrow therapeutic window, variable dose response, multiple interactions with other drugs and concurrent illnesses, and the need for frequent laboratory monitoring. In recent years, the direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban and edoxaban, have been developed to overcome the limitations of warfarin therapy. These treatment strategies are either comparable or superior to warfarin in stroke prevention in AF. Despite the documented effectiveness of oral anticoagulants in AF, patients may not derive optimal benefit if they fail to adhere or fail to continue with their medication. This may lead to treatment failure, increased hospitalization and mortality. This review summarizes the literature regarding adherence and persistence (or discontinuation) rates with oral anticoagulants in the management of AF; the impact of non-adherence and non-persistence on treatment outcomes; and the effectiveness of strategies to improve adherence and persistence with oral anticoagulant therapy. PMID- 27262431 TI - Pharmacological Beta-Adrenergic Receptor Activation Attenuates Neutrophil Recruitment by a Mechanism Dependent on Nicotinic Receptor and the Spleen. AB - The aim of this study was to identify the effect of beta-adrenergic receptor activation on neutrophil migration in experimental peritonitis elucidating the neuroimmune components involved such as nicotinic receptors and the spleen. Mice pre-treated with mecamylamine (nicotinic antagonist) and propranolol (beta adrenergic antagonist) or splenectomized animals were treated with isoproterenol (beta-adrenergic agonist) prior to intraperitoneal injection of carrageenan. After 4 h, the infiltrating neutrophils and the local cytokine/chemokine levels were evaluated in the peritoneal lavage. The effect of isoproterenol on neutrophil chemotaxis was investigated in a Boyden chamber. Isoproterenol inhibited neutrophil trafficking, reducing the cytokine/chemokine release and neutrophil chemotaxis. Surprisingly, the isoproterenol effect on neutrophil migration was totally reverted by splenectomy and mecamylamine pre-treatment. In contrast, the inhibitory effect of nicotine on neutrophil migration was abrogated only by splenectomy but not by propranolol pre-treatment. Collectively, our data show that beta-adrenergic receptor activation regulates the acute neutrophil recruitment via splenic nicotinic receptor. PMID- 27262434 TI - Beneficial native bacteria improve survival and mycorrhization of desert truffle mycorrhizal plants in nursery conditions. AB - Sixty-four native bacterial colonies were isolated from mycorrhizal roots of Helianthemum almeriense colonized by Terfezia claveryi, mycorrhizosphere soil, and peridium of T. claveryi to evaluate their effect on mycorrhizal plant production. Based on the phylogenetic analysis of the 16S rDNA partial sequence, 45 different strains from 17 genera were gathered. The largest genera were Pseudomonas (40.8 % of the isolated strains), Bacillus (12.2 % of isolated strains), and Varivorax (8.2 % of isolated strains). All the bacteria were characterized phenotypically and by their plant growth-promoting rhizobacteria (PGPR) traits (auxin and siderophore production, phosphate solubilization, and ACC deaminase activity). Only bacterial combinations with several PGPR traits or Pseudomonas sp. strain 5, which presents three different PGPR traits, had a positive effect on plant survival and growth. Particularly relevant were the bacterial treatments involving auxin release, which significantly increased the root-shoot ratio and mycorrhizal colonization. Moreover, Pseudomonas mandelii strain 29 was able to considerably increase mycorrhizal colonization but not plant growth, and could be considered as mycorrhiza-helper bacteria. Therefore, the mycorrhizal roots, mycorrhizosphere soil, and peridium of desert truffles are environments enriched in bacteria which may be used to increase the survival and mycorrhization in the desert truffle plant production system at a semi-industrial scale. PMID- 27262435 TI - Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. AB - The selenoenzyme glutathione peroxidase 4 (Gpx4) is an essential mammalian glutathione peroxidase, which protects cells against detrimental lipid peroxidation and governs a novel form of regulated necrotic cell death, called ferroptosis. To study the relevance of Gpx4 and of another vitally important selenoprotein, cytosolic thioredoxin reductase (Txnrd1), for liver function, mice with conditional deletion of Gpx4 in hepatocytes were studied, along with those lacking Txnrd1 and selenocysteine (Sec) tRNA (Trsp) in hepatocytes. Unlike Txnrd1 and Trsp-deficient mice, Gpx4-/- mice died shortly after birth and presented extensive hepatocyte degeneration. Similar to Txnrd1-deficient livers, Gpx4-/- livers manifested upregulation of nuclear factor (erythroid-derived)-like 2 (Nrf2) response genes. Remarkably, Gpx4-/- pups born from mothers fed a vitamin E enriched diet survived, yet this protection was reversible as subsequent vitamin E deprivation caused death of Gpx4-deficient mice ~4 weeks thereafter. Abrogation of selenoprotein expression in Gpx4-/- mice did not result in viable mice, indicating that the combined deficiency aggravated the loss of Gpx4 in liver. By contrast, combined Trsp/Txnrd1-deficient mice were born, but had significantly shorter lifespans than either single knockout, suggesting that Txnrd1 plays an important role in supporting liver function of mice lacking Trsp. In sum our study demonstrates that the ferroptosis regulator Gpx4 is critical for hepatocyte survival and proper liver function, and that vitamin E can compensate for its loss by protecting cells against deleterious lipid peroxidation. PMID- 27262436 TI - Genomic selection for wheat traits and trait stability. AB - KEY MESSAGE: Based on the estimates of accuracy, genomic selection would be useful for selecting for improved trait values and trait stability for agronomic and quality traits in wheat. Trait values and trait stability estimated by two methods were generally independent indicating a breeder could select for both simultaneously. Genomic selection (GS) is a new marker-assisted selection tool for breeders to achieve higher genetic gain faster and cheaper. Breeders face challenges posed by genotype by environment interaction (GEI) pattern and selecting for trait stability. Obtaining trait stability is costly, as it requires data from multiple environments. There are few studies that evaluate the efficacy of GS for predicting trait stability. A soft winter wheat population of 273 lines was genotyped with 90 K single nucleotide polymorphism markers and phenotyped for four agronomic and seven quality traits. Additive main effect and multiplicative interaction (AMMI) model and Eberhart and Russell regression (ERR) were used to estimate trait stability. Significant GEI variation was observed and stable lines were identified for all traits in this study. The accuracy of GS ranged from 0.33 to 0.67 for most traits and trait stability. Accuracy of trait stability was greater than trait itself for yield (0.44 using AMMI versus 0.33) and heading date (0.65 using ERR versus 0.56). The opposite trend was observed for the other traits. GS did not predict the stability of the quality traits except for flour protein, lactic acid and softness equivalent. Significant GS accuracy for some trait stability indicated that stability was under genetic control for these traits. The magnitude of GS accuracies for all the traits and most of the trait stability index suggests the possibility of rapid selection for these trait and trait stability in wheat breeding. PMID- 27262437 TI - The crystal structure of an inactive dimer of PDZ-binding kinase. AB - The overexpression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) has been associated with hematologic tumors, breast cancer and various other cancers. However, the three-dimensional structure of PBK has not been solved. In this study, we determined the crystal structure of human PBK, which has two phospho-mimicking mutations T9E and T198E. The structural data indicated that PBK may assemble into an inactive dimer in alkaline conditions. Analytical size-exclusion chromatography and analytical ultracentrifugation confirmed that PBK exists in a conformational transition between dimers and monomers at different pH conditions. Co-IP and kinase assays suggested that the active state of PBK is a monomer and does not form a dimer even under alkaline conditions. These results showed that the conformational transition of PBK is important for its kinase activity regulation. Collectively, our observations may provide a novel starting point for structure-based functional studies. PMID- 27262438 TI - MiR-485 inhibits metastasis and EMT of lung adenocarcinoma by targeting Flot2. AB - Lung adenocarcinoma, as a common form of non-small cell lung cancer, poses a significant threat to public health worldwide. Previous studies have reported that flotillin-2 (Flot2) is often overexpressed in various tumors and is h correlated with tumor progression and patient survival. Dysregulated microRNA (miRNA) is associated with various cancers, including lung adenocarcinoma. However, little is known about the miRNAs targeting Flot2 in lung adenocarcinoma. In this study, we found that the expression level of miR-485 was downregulated in four lung adenocarcinoma cell lines and tissues and that the reduced miR-485 expression was associated with tumor metastasis. Luciferase assay revealed that Flot2 is direct target of miR-485, while the expression levels of Flot2 were inversely correlated with the expression levels of miR-485 in lung adenocarcinoma tissues. Ectopic Flot2 could significantly reverse miR-485-mediated inhibition of metastasis and EMT, demonstrating Flot2 downregulation is involved in function of miR-485. Subsequently, we found that miR-485 suppressed the activity of PI3K/AKT/mTOR signaling in lung adenocarcinoma cells. In conclusion, the present study provided novel insight into the molecular mechanism of lung adenocarcinoma progression and demonstrating miR-485 as a potential therapeutic target in human lung adenocarcinoma. PMID- 27262439 TI - Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis. AB - Iron is an essential nutrient for every type of life on earth. However, excess iron is cytotoxic and can lead to an increased cancer risk in humans. Catalytic ferrous iron [Fe(II)] is an initiator of the Fenton reaction, which causes oxidative stress by generating hydroxyl radicals. Recently, it became possible to localize catalytic Fe(II) in situ with a turn-on fluorescent probe, RhoNox-1. Here, we screened each organ/cell of rats to globally evaluate the distribution of catalytic Fe(II) and found that eosinophils showed the highest abundance. In various cells, lysosomes were the major organelle, sharing ~40-80% of RhoNox-1 fluorescence. We then used an ovalbumin-induced allergic peritonitis model to study the dynamics of catalytic Fe(II). Peritoneal lavage revealed that the total iron contents per cell were significantly decreased, whereas an increase in the number of inflammatory cells (macrophages, neutrophils, eosinophils and lymphocytes) resulted in an increased total iron content of the peritoneal inflammatory cells. Notably, macrophages, eosinophils and neutrophils exhibited significantly increased catalytic Fe(II) with increased DMT1 expression and decreased ferritin expression, though catalytic Fe(II) was significantly decreased in the peritoneal lavage fluid. In conclusion, catalytic Fe(II) in situ more directly reflects cellular activity and the accompanying pathology than total iron does. PMID- 27262440 TI - Increased copper toxicity in Saccharomyces cerevisiae lacking VPS35, a component of the retromer and monogenic Parkinson disease gene in humans. AB - The Saccharomyces cerevisiae gene VPS35 encodes a component of the retromer complex which is involved in vesicle transport from endosomes to the trans-Golgi network. Yeast and human VPS35 orthologs are highly conserved and mutations in human VPS35 cause an autosomal dominant form of late-onset Parkinson disease (PD). We now show that deletion of VPS35 in yeast (vps35Delta) leads to a dose dependent growth defect towards copper. This increased sensitivity could be rescued by transformation with yeast wild-type VPS35 but not by the expression of a construct harboring the yeast equivalent (i.e. D686N) of the most commonly identified VPS35-associated PD mutation, p.D620N. In addition, we show that expression of one copy of alpha-synuclein, which is known to directly interact with copper, leads to a pronounced aggravation of copper toxicity in vps35Delta cells, thereby linking the regulation of copper homeostasis by Vps35p in yeast to one of the key molecules in PD pathophysiology. PMID- 27262443 TI - Physical activity during school and after school among youth with and without intellectual disability. AB - BACKGROUND: Little is known about physical activity (PA) among children with intellectual disability (ID) or their reasons to take part in PA and sport. AIMS: To investigate PA and PA patterns during school and after school among Icelandic children with mild-to-severe ID. METHODS AND PROCEDURES: Ninety-one children with ID and a matched group of 93 typically developed individuals (TDI) took part. PA was assessed with accelerometers and a questionnaire was used to collect data on PA behavior. RESULTS AND OUTCOMES: TDI children were more active and less sedentary than children with ID (p<0.001). Both sexes with ID were more active and less sedentary during school than after school (p<0.003) but no difference was found among TDI children. Children with ID (60%) were more likely to name weight loss as a reason to participate in PA than TDI children (34%, p=0.002) but a higher proportion (96%) of TDI children than children with ID (50%) participated in PA to improve skills (p<0.001). CONCLUSION AND IMPLICATIONS: Children with ID depend more on schools to accumulate their PA and their reasons for PA participation differ from TDI children. This needs to be considered when designing and implementing PA promotion campaigns for children with ID. PMID- 27262441 TI - Effect of mild temperature shift on poly(ADP-ribose) and gammaH2AX levels in cultured cells. AB - Poly (ADP-ribose) (PAR) is rapidly synthesized by PAR polymerases (PARPs) upon activation by DNA single- and double-strand breaks. In this study, we examined the quantitative amount of PAR in HeLa cells cultured within the physiological temperatures below 41 degrees C for verification of the effect of shifting-up or -down the temperature from 37.0 degrees C on the DNA breaks, whether the temperature-shift caused breaks that could be monitored by the level of PAR. While PAR level did not change significantly when HeLa cells were cultured at 33.5 degrees C or 37.0 degrees C, it was significantly increased 2- and 3-fold when cells were cultured for 12 h and 24 h, respectively, at 40.5 degrees C as compared to 37.0 degrees C. Similar to the results with HeLa cells, PAR level was increased 2-fold in CHO-K1 cells cultured at 40.5 degrees C for 24 h as compared to 37.0 degrees C. As the cellular levels of PAR polymerase1 (PARP1) and PAR glycohydrolase (PARG), a major degradation enzyme for PAR, did not seem to change significantly, this increase could be caused by activation of PARP1 by DNA strand breaks. In fact, gammaH2AX, claimed to be a marker of DNA double strand breaks, was found in cell extracts of HeLa cells and CHO-K1 cells at elevated temperature vs. 37.0 degrees C, and these gammaH2AX signals were intensified in the presence of 3-aminobenzamide, a PARP inhibitor. The gammaH2AX immunohistochemistry results in HeLa cells were consistent with Western blot analyses. In HeLa cells, proliferation was significantly suppressed at 40.5 degrees C in 72 h-continuous cultures and decreased viabilities were also observed after 24-72 h at 40.5 degrees C. Flow cytometric analyses showed that the HeLa cells were arrested at G2/M after temperature shift-up to 40.5 degrees C. These physiological changes were potentiated in the presence of 3 aminobenzamide. Decrease in growth rates, increased cytotoxicity and G2/M arrest, were associated with the temperature-shift to 40.5 degrees C and are indirect evidence of DNA breaks. In addition to gammaH2AX, PAR could be a sensitive marker for DNA single- and double-strand breaks. These two molecular markers provide evidence of physiological changes occurring within cells. PMID- 27262442 TI - Benzimidazole Based 'Turn on' Fluorescent Chemodosimeter for Zinc Ions in Mixed Aqueous Medium. AB - Benzimidazole based compound 3 is designed and synthesized. The compound 3 is evaluated as fluorogenic sensor for metal ions in mixed aqueous solutions. Among all the metal ions tested, the compound 3 selectively senses Zn(2+) ions. The imine bond of 3 gets cleaved by Zn(2+) ions. Thus, 3 behave as 'turn on' fluorescent chemodosimeter for Zn(2+) ions with limit of detction in micromolar range. Furthurmore, we demonstated that 3 can detect Zn(2+) ions in cells of Allium cepa. Graphical Abstract Benzimidazole based ligand 3 is designed and synthesized which behave as chemodosimeter for Zn(2+) ions. We further demonstrated that 3 can detect Zn(2+) ions in cells of Allium cepa. PMID- 27262444 TI - The socio-behavioral development of children with symptoms of attachment disorder: An observational study of teacher sensitivity in special education. AB - BACKGROUND: Children with Reactive Attachment Disorder (RAD) have serious socio behavioral problems and often rely on socially abnormal, aggressive, and manipulative forms of communication. Little is known, however, about the influence of teachers on the socio-behavioral development of children with symptoms of RAD. AIMS: This longitudinal study examined the influence of teacher sensitivity on the socio-behavioral development of children with symptoms of RAD across one school year. METHOD: The sample included 85 Belgian children and 70 teachers from special education schools. In the previous school year, teachers rated Inhibited and Disinhibited RAD symptoms. In the next school year, teacher Sensitivity was observed in interactions with individual children in the first trimester. Teacher-rated Overt aggression, Relational aggression, and Prosocial behavior was assessed in the first, second, and third trimester. RESULTS: We found no effects of Sensitivity on Prosocial behavior. Also, no effects were found for children with Disinhibited RAD symptoms. For children with Inhibited RAD symptoms, increases in Overt and Relational aggression were observed when Sensitivity was low, whereas decreases were observed when Sensitivity was high. CONCLUSIONS AND IMPLICATIONS: The results suggest that teacher sensitivity is associated with the socio-behavioral development of children with Inhibited RAD symptoms but not with the socio-behavioral development of children with Disinhibited RAD symptoms. WHAT THIS PAPER ADDS: Children with Reactive Attachment Disorder (RAD) exhibit socio-behavioral problems that hinder their school adjustment. These socio-behavioral problems appear relatively stable and it is not known what influence special education teachers might have on the development of these problems across a school year. This study suggests that teacher sensitivity is associated with changes in the socio-behavioral development of children with Inhibited RAD symptoms. Whereas high sensitivity was associated with improvements, low sensitivity appeared to exaggerate the socio behavioral problems of these children. As children with Inhibited RAD symptoms have difficulties communicating their needs and wishes in socially adaptive ways, it may not be easy for teachers to understand these children. Teachers may misinterpret a child's behavior and consequently will fail to respond to the child's underlying needs. This may reinforce the child's socio-behavioral problems and increase the child's reliance on egocentric and aggressive means in interactions with others. This study therefore highlights the need to support teachers in interactions with children with Inhibited RAD symptoms in order to help them understand how the children's observable behaviors in the classroom may convey their underlying socio-emotional needs and how they can respond to these needs. Importantly, teacher sensitivity was not associated with the socio behavioral development of children with Disinhibited RAD symptoms (e.g., indiscriminate friendliness). Consistent with previous research, this study suggests that children with Inhibited RAD symptoms are more susceptible to the quality of the caregiving environment than children with Disinhibited RAD symptoms and extends this finding to the school context. PMID- 27262445 TI - Measuring intellectual ability in cerebral palsy: The comparison of three tests and their neuroimaging correlates. AB - Standard intelligence scales require both verbal and manipulative responses, making it difficult to use in cerebral palsy and leading to underestimate their actual performance. This study aims to compare three intelligence tests suitable for the heterogeneity of cerebral palsy in order to identify which one(s) could be more appropriate to use. Forty-four subjects with bilateral dyskinetic cerebral palsy (26 male, mean age 23 years) conducted the Raven's Coloured Progressive Matrices (RCPM), the Peabody Picture Vocabulary Test-3rd (PPVT-III) and the Wechsler Nonverbal Scale of Ability (WNV). Furthermore, a comprehensive neuropsychological battery and magnetic resonance imaging were assessed. The results show that PPVT-III gives limited information on cognitive performance and brain correlates, getting lower intelligence quotient scores. The WNV provides similar outcomes as RCPM, but cases with severe motor impairment were unable to perform it. Finally, the RCPM gives more comprehensive information on cognitive performance, comprising not only visual but also verbal functions. It is also sensitive to the structural state of the brain, being related to basal ganglia, thalamus and white matter areas such as superior longitudinal fasciculus. So, the RCPM may be considered a standardized easy-to-administer tool with great potential in both clinical and research fields of bilateral cerebral palsy. PMID- 27262446 TI - Innovation in the management of intensive care units: This is the right time. PMID- 27262447 TI - Dietary inflammatory index and ovarian cancer risk in a large Italian case control study. AB - BACKGROUND: While inflammation has been shown to play an important etiologic role in ovarian carcinogenesis, little is known about the association between inflammatory properties of diet and ovarian cancer risk. METHODS: We explored the association between the dietary inflammatory index (DII) and ovarian cancer risk in a multicentric Italian case-control study conducted between 1992 and 1999. Cases were 1,031 women with incident, histologically confirmed ovarian cancer from four areas in Italy. Controls were 2,411 women admitted to the same network of hospitals as the cases for acute, non-malignant and non-gynecological conditions, unrelated to hormonal or digestive-tract diseases or committed to long-term modifications of diet. DII scores were computed based on 31 nutrients and food items assessed using a reproducible and validated 78-item food frequency questionnaire. Odds ratios (ORs) were estimated through logistic regression models adjusting for age, total energy intake and other recognized confounding factors. RESULTS: Subjects in the highest quartile of DII scores (i.e., with the most pro-inflammatory diets) had a higher risk of ovarian cancer compared to subjects in the lowest quartile (i.e., with an anti-inflammatory diet) (ORQuartile4vs1 1.47, 95% confidence interval, CI, 1.07, 2.01; p trend = 0.009). When analyses were carried out using continuous DII, a significant positive association with ovarian cancer was observed: the OR for one-unit increment in DII score (corresponding to approximately 8 % of its range in the current study, +6.0 to -6.20) was 1.08 (95% CI 1.02, 1.14). CONCLUSION: A pro-inflammatory diet as indicated by higher DII scores is associated with increased ovarian cancer risk. PMID- 27262448 TI - Linkage Study Revealed Complex Haplotypes in a Multifamily due to Different Mutations in CAPN3 Gene in an Iranian Ethnic Group. AB - Calpainopathy is an autosomal recessive form of limb girdle muscular dystrophies which is caused by mutation in CAPN3 gene. In the present study, co-segregation of this disorder was analyzed with four short tandem repeat markers linked to the CAPN3 gene. Three apparently unrelated Iranian families with same ethnicity were investigated. Haplotype analysis and sequencing of the CAPN3 gene were performed. DNA sample from one of the patients was simultaneously sent for next-generation sequencing. DNA sequencing identified two mutations. It was seen as a homozygous c.2105C>T in exon 19 in one family, a homozygous novel mutation c.380G>A in exon 3 in another family, and a compound heterozygote form of these two mutations in the third family. Next-generation sequencing also confirmed our results. It was expected that, due to the rare nature of limb girdle muscular dystrophies, affected individuals from the same ethnic group share similar mutations. Haplotype analysis showed two different homozygote patterns in two families, yet a compound heterozygote pattern in the third family as seen in the mutation analysis. This study shows that haplotype analysis would help in determining presence of different founders. PMID- 27262449 TI - Origin of the thalamic projection to dorsal auditory cortex in hearing and deafness. AB - While it is now well accepted that the brain reorganizes following sensory loss, the neural mechanisms that give rise to this plasticity are not well understood. Anatomical tract tracing studies have begun to shed light on the structural underpinnings of cross-modal reorganization by comparing cerebral connectivity in sensory-deprived animals to that of their non-deprived counterparts. However, so far, full documentation of connectional patterns within hearing, congenitally deaf, as well as animals deafened early versus later in life exist only for primary auditory cortex, a region not known to undergo cross-modal reorganization in the deaf. The purpose of the present investigation was to examine thalamo cortical patterns of connectivity in hearing, late- and early-deafened cats to the dorsal zone (DZ), a region of auditory cortex that cross-modally reorganizes to mediate enhanced visual motion perception following deafness. In hearing cats, the largest projections to DZ arose from the dorsal division of the medial geniculate body (MGB) with lesser projections originating in the medial and ventral MGB and from the suprageniculate and the lateral posterior nuclei. In general, while some variations in the strength of specific thalamic projections were noted, the pattern of projections arising from the thalamus in early- and late-deafened animals remained consistent with that of hearing subjects. These results complement the existing thalamic connectivity data described for congenitally deaf animals, which together demonstrate that thalamo-cortical connectivity patterns to DZ are conserved following deafness, irrespective of the time of onset and etiology of deafness. PMID- 27262450 TI - Detection efficiency of auditory steady state evoked by modulated noise. AB - AIM: This study aimed to investigate the efficiency of Magnitude Squared Coherence (MSC) and Spectral F test (SFT) for the detection of auditory steady state responses (ASSR) obtained by amplitude-modulated noises. MATERIAL AND METHODS: Twenty individuals (12 women) without any history of neurological or audiological diseases, aged from 18 to 59 years (mean +/- standard deviation = 26.45 +/- 3.9 years), who provided written informed consent, participated in the study. The Audiostim system was used for stimulating and ASSR recording. The tested stimuli were amplitude-modulated Wide-band noise (WBN), Low-band noise (LBN), High-band noise (HBN), Two-band noise (TBN) between 77 and 110 Hz, applied in intensity levels of 55, 45, and 25 dB sound pressure level (SPL). MSC and SFT, two statistical-based detection techniques, were applied with a significance level of 5%. Detection times and rates were compared using the Friedman test and Tukey-Kramer as post hoc analysis. Also based on the stimulation parameters (stimuli types and intensity levels) and detection techniques (MSC or SFT), 16 different pass/fail protocols, for which the true negatives (TN) were calculated. RESULTS: The median detection times ranged from 68 to 157s for 55 dB SPL, 68-99s for 45 dB SPL, and 84-118s for 25 dB SPL. No statistical difference was found between MSC and STF considering the median detection times (p > 0.05). The detection rates ranged from 100% to 55.6% in 55 dB SPL, 97.2%-38.9% in 45 dB SPL and 66.7%-8.3% in 25 dB SPL. Also for detection rates, no statistical difference was observed between MSC and STF (p > 0.05). True negatives (TN) above 90% were found for Protocols that employed WBN or HBN, at 55 dB SPL or that used WBN or HBN, at 45 dB SPL. For Protocols employing TBN, at 55 dB SPL or 45 dB SPL TN below 60% were found due to the low detection rates of stimuli that included low band frequencies. CONCLUSION: The stimuli that include high-frequency content showed higher detection rates (>90%) and lower detection times (<3 min). The noise composed by two bands applied separately (TBN) is not feasible for clinical applications since it requires prolonging the exam duration, and also led to a reduced percentage of true negatives. On the other hand, WBN and HBN achieved high detection performance and high TN and should be investigated to implement pass/fail protocol for hearing screening with clinical population. Finally, both WBN and HBN seemed to be indifferent to the employed technique (SFT or MSC), which can be seen as another advantage of ASSR employment. PMID- 27262451 TI - Comparison of Extracellular Matrix Patch and Standard Patch Material in the Pulmonary Arteries. AB - After pulmonary artery (PA) patch augmentation, surgical or catheterization reintervention to address PA stenosis is not uncommon. Multiple patch materials are available and the need for reintervention may be related to characteristics of the patch material. In this retrospective chart review of patients who underwent PA augmentation from 2004 through 2013, we compare outcomes after PA augmentation with standard patch (SP) material and extracellular matrix (ECM) patch material. The primary outcome was reintervention-free survival (surgery or catheterization) using Kaplan-Meier survival analysis with the log-rank test. Risk factors for reintervention were assessed with Cox proportional hazard analyses. Baseline characteristics between groups were similar, except single ventricle (SV) patients were more likely to have SP, and duration of follow-up was longer in the SP group. Median time to reintervention for all patients was 1099 days (95 % CI 646-1552 days). There was no difference in reintervention-free survival between the patch groups (p = 0.12); however, in multivariable analysis controlling for surgeon and patch, longer reintervention-free survival was associated with SV physiology (HR 0.57 95 % CI 0.34-0.95, p = 0.03) and aortic cross-clamp (XC) use (HR 0.52, 95 % CI 0.32-0.84, p = 0.008). Since there is no difference in median time to reintervention following PA augmentation with SP or ECM, patch choice should be determined by other factors, such as surgeon preference and cost. Longer reintervention-free survival in SV patients may be related to the set schedule of staged palliation. XC use may allow more extensive PA augmentation, thus protecting against the need for reintervention. PMID- 27262452 TI - Real-World Effectiveness and Safety of a Live-Attenuated Herpes Zoster Vaccine: A Comprehensive Review. AB - Herpes zoster (HZ) is a common, painful and debilitating disease caused by the reactivation of latent varicella-zoster virus in ganglia. This clinical event occurs more frequently in the elderly and those who are immunocompromised. The most common complication of HZ is post-herpetic neuralgia (PHN) which is responsible for the highest HZ-related burden of illness and is challenging to treat. Due to the important clinical and economic impact of HZ and PHN, and the suboptimal treatments that are currently available, HZ vaccination is an important approach to reduce the burden of illness. Currently, one-dose, live attenuated vaccine is licensed in the United States and Europe to prevent HZ and it is included in some national immunization programs. The clinical efficacy, safety and tolerability of the vaccine has been demonstrated in two large phase III clinical trials, involving more than 38,000 and 22,000 individuals aged >=60 and 50-59 years, respectively. This comprehensive review summarizes the extensive "real-world" effectiveness and safety data from both immunocompetent and immunocompromised individuals. These data confirm those from the clinical trials, supporting the use of HZ vaccine in clinical practice and provide evidence that the current recommendations for immunocompromised individuals should be revised. FUNDING: Funding for the editorial assistance, article processing charges, and open access fee for this publication was provided by Sanofi Pasteur MSD. PMID- 27262453 TI - Enhancing NK cell cytotoxicity by miR-182 in hepatocellular carcinoma. AB - BACKGROUND AND AIM: NK-cells are the principle defense line against different malignancies. Their activation status is determined by the balance between activating and inhibitory receptors such as NKG2D and NKG2A, respectively. MicroRNAs are crucial post-transcriptional regulators of gene expression, playing key roles in modulating NK-cell development and function. The aim of this study is to investigate the role of miRNAs in regulating the activation and cytotoxic function of NK-cells in HCC. METHODS: In silico analysis was performed to predict a potential miRNA that might target NKG2D and NKG2A mRNAs. NK-cells were isolated from HCC patients and healthy controls, after which miRNA and mRNA were quantified. Manipulating miRNA expression was performed followed by investigating downstream targets and the cytotoxic activity of NK-cells against Huh-7 cell lines. RESULTS: NK-cells of HCC patients showed miR-182 overexpression compared to controls. NKG2D and NKG2A were upregulated and downregulated, respectively, in HCC NK-cells. Upon forcing miR-182 expression in the HCC NK-cells, upregulation of both receptors was observed. Finally, miR-182 was reported to induce NK-cell cytotoxicity represented in Perforin-1 upregulation and increase in cytolytic killing of co-cultured Huh-7 cells. CONCLUSION: Our findings suggest that miR-182 may augment NK-cell cytotoxicity against liver cancer via modulating NKG2D and NKG2A expressions. PMID- 27262454 TI - HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in a population of 432 healthy unrelated individuals from Albania. AB - This paper reports the HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype polymorphism in a population of 432 healthy individuals from Albania. First-field HLA genotyping was performed by polymerase chain reaction sequence-specific priming and/or oligonucleotide methods. The data were analyzed statistically using gene counting and Arlequin software packages. No deviation from Hardy Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database and they can serve as a reference database for further HLA-based population genetics studies including the Albanian population. PMID- 27262456 TI - Marijuana-Related Posts on Instagram. AB - Instagram is a highly visual social networking site whose audience continues to grow, especially among young adults. In the present study, we examine marijuana related content on Instagram to better understand the varied types of marijuana related social networking occurring on this popular social media platform. We collected 417,561 Instagram posts with marijuana-related hashtags from November 29 to December 12, 2014. We assessed content of a random sample (n = 5000) of these posts with marijuana-related hashtags. Approximately 2136 (43 %) were explicit about marijuana and further analyzed. Of the 2136 marijuana-related posts, images of marijuana were common (n = 1568). Among these 1568 marijuana images, traditional forms (i.e., buds/leaves) were the most common (63 %), followed by some novel forms of marijuana, including marijuana concentrates (20 %). Among the 568 posts that displayed marijuana being ingested, 20 % showed someone dabbing marijuana concentrates. Marijuana-related advertisements were also observed among the 2136 marijuana-related posts (9 %). Our findings signal the promotion of marijuana use in its traditional plant-based form; trendy and novel modes of marijuana ingestion were also endorsed. This content along with the explicit marketing of marijuana that we observed on Instagram have potential to influence social norms surrounding marijuana use. PMID- 27262455 TI - Multidimensional reduction of multicentric cohort heterogeneity: An alternative method to increase statistical power and robustness. AB - Modern clinical research takes advantage of multicentric cohorts to increase sample size and gain in statistical power. However, combining individuals from different recruitment centers provides heterogeneity in the dataset that needs to be accounted for to obtain robust results. Sophisticated statistical multivariate models adjusting for center effect can be implemented, but they can become unstable and can be complex to interpret with the increasing number of covariates to consider. Here, we present a multidimensional reduction technique to identify heterogeneity in a French multicentric cohort of hematopoietic stem cell transplantations and characterize a homogeneous subgroup prior to performing simple statistical univariate analyses. The exclusion of outliers allowed the identification of two genetic factors associated with post-transplantation overall survival. We therefore provide proof-of-concept that a sample size reduction method can efficiently account for heterogeneity and center effect in multicentric cohorts while increasing statistical power and robustness for discovery of new association signals. PMID- 27262457 TI - The effect of resin coating on the shear punch strength of restorative glass ionomer cements. AB - OBJECTIVE: The aim of the current study was to examine the shear punch strength (SPS) of high-strength glass ionomer cements (HSGICs) in relation to coating applications and duration of coating. MATERIALS AND METHODS: I-Ninety specimens each of Fuji IX GP Fast (FIX Fast), Ionofil Molar AC (IM), Riva Self Cure (R) and Ketac Molar (KM) were prepared and divided into uncoated and coated groups, sub divided into three sub-groups and incubated for 24 h, 1 week or 8 weeks (distilled water, 37 degrees C) before SPS. II-Ninety specimens each of uncoated and coated Fuji IX GP Extra were similarly prepared, divided into six sub-groups and incubated for 2 h, 24 h, 1 week, 1 month, 2 months or 3 months (artificial saliva, 37 degrees C) before SPS. Another 90 specimens were coated for 2 h, 24 h, 1 week, 1 month or 2 months, after which the coating was removed. Specimens were re-incubated in artificial saliva until the end of the 3-month period and then subjected to SPS. RESULTS: None of the materials gained extra strength when coated. Uncoated KM, IM (at all times) and FIX Fast (at 24 h) were stronger. Fuji IX GP Extra achieved 11.5 MPa after 2 h, which increased to 56.7 MPa after 24 h. The highest strength after 3 months was achieved when the coating was retained for 2 h (71.7 MPa). CONCLUSION: A resin coating will not positively affect the SPS of HSGICs. CLINICAL RELEVANCE: There is no need to protect HSGICs from water to gain extra strength unless the coating is retained for 2 h. PMID- 27262458 TI - Neighbourhood search feature selection method for content-based mammogram retrieval. AB - Content-based image retrieval plays an increasing role in the clinical process for supporting diagnosis. This paper proposes a neighbourhood search method to select the near-optimal feature subsets for the retrieval of mammograms from the Mammographic Image Analysis Society (MIAS) database. The features based on grey level cooccurrence matrix, Daubechies-4 wavelet, Gabor, Cohen-Daubechies-Feauveau 9/7 wavelet and Zernike moments are extracted from mammograms available in the MIAS database to form the combined or fused feature set for testing various feature selection methods. The performance of feature selection methods is evaluated using precision, storage requirement and retrieval time measures. Using the proposed method, a significant improvement is achieved in mean precision rate and feature dimension. The results show that the proposed method outperforms the state-of-the-art feature selection methods. PMID- 27262459 TI - Efficacy of vacuum-assisted closure therapy on rehabilitation during the treatment for surgical site infection after cardiovascular surgery. AB - OBJECTIVE: Surgical site infection (SSI) after cardiovascular procedures is a severe complication, potentially leading to high morbidity and mortality. In addition, during the treatment of SSI, rehabilitation is delayed, which can severely impair postoperative recovery. The aim of this study was to assess the effect of vacuum-assisted closure (VAC) therapy on rehabilitation during the treatment of SSI after cardiovascular surgery. METHODS: From January 2008 to March 2015, 10 patients underwent VAC therapy for SSI after cardiovascular operations. The patient characteristics, duration of VAC therapy, time interval from the implementation of VAC to physical therapy (PT) (T1), ambulation (T2) and walking (T3), functional independent measure (FIM), and maximum consecutive walking capacity (MCWC) were retrospectively analyzed. RESULTS: Nine patients underwent mid-sternal incision and one patient underwent thoraco-abdominal incision. The mean time interval from the beginning of VAC therapy to PT, ambulation, and walking was 0.38 +/- 0.50, 0.63 +/- 0.71, and 1.38 +/- 1.86 days, respectively. The average FIM was 84.5 +/- 14.0 at the beginning of VAC therapy and 106.7 +/- 18.5 at the end of VAC therapy (P = 0.000494). On average, MCWC was 52.3 +/- 54.6 m at the installation of VAC therapy and 189.7 +/- 152.8 m at the completion of VAC therapy (P = 0.0169). FIM and MCWC improvement rate was better in VAC group than non-VAC group although these data are not suitable for statistical analysis because of a small sample size. CONCLUSIONS: Although further studies are warranted, VAC therapy may have a role in facilitating rehabilitation and improving the prognosis of SSI cases after major cardiovascular operations. PMID- 27262460 TI - Description of Sphingomonas mohensis sp. nov., Isolated from Sediment. AB - An aerobic, gram-reaction-negative, rod-shaped bacterium, designated strain Z6(T), was isolated from sediment collected at Mohe Basin, China. And its taxonomic position was investigated by applying a polyphasic approach. Growth occurs at 10-45 degrees C (optimum, 30 degrees C), at pH 6.0-11.0 (optimum, pH 7.0) and in the presence of 0-3.0 % (w/v) NaCl (optimum, 0 %). The polar lipid profile of strain Z6(T) revealed the presence of diphosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid and two unidentified phospholipids, and the major quinone was Q-10. The major fatty acids were C18:1 omega7c and/or C18:1 omega6c (summed feature 8) and C16:1 omega6c and/or C16:1 omega7c (summed feature 3). The predominant polyamine was homospermidine. The DNA G + C content of strain Z6(T) is 65.2 mol%. On the basis of the polyphasic evidence presented, strain Z6(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas mohensis sp. nov. is proposed. The type strain is Z6(T) (=CGMCC 1.12891(T) = JCM 19983(T)). PMID- 27262461 TI - Protective Effects of Extracellular and Intracellular Polysaccharides on Hepatotoxicity by Hericium erinaceus SG-02. AB - The protective effects of extracellular and intracellular polysaccharides from Hericium erinaceus SG-02 on the CCl4-induced hepatic injury of mice were investigated in this work. By the analysis of GC, the extracellular polysaccharides (EPS) were composed of arabinose, mannose, galactose, and glucose with a ratio of 1:7:14:52, and the composition of intracellular polysaccharides (IPS) was rhamnose, xylose, mannose, galactose, and glucose with a ratio of 3:4:7:14:137. The model of hepatic injury of mice was induced by CCl4 and three tested levels (200, 400, and 800 mg/kg) of EPS and IPS were set as the experimental group. Results showed that the aspartate aminotransferase and glutamic pyruvic transaminase activities in serum were reduced by the supplement of EPS and IPS, while the blood lipid levels including cholesterol, triglyceride, and albumin were improved. In liver tissue, the lipid peroxidation and malondialdehyde were largely decreased, and the superoxide dismutase and catalase activities were significantly increased. The evidence demonstrated that the EPS and IPS of H. erinaceus SG-02 were protective for liver injury. The histopathological observations of mice liver slices indicated that EPS and IPS had obvious effects on liver protection. PMID- 27262463 TI - Is Too Much Enough? AB - When the Elwood boys advanced beyond the toddler stage and acquired a prolific ability to wreak havoc on their domestic surroundings, this Journal's editor would try in vain to reduce the amount of destruction by offering the following sage parental advice, "Too much is enough boys, too much is enough." Although the words produced little effect, they have remained with this editor over the decades, particularly in the context of the exponential growth in the number of periodicals and the manuscripts contained in them. It is estimated that there are more than 34,000 scientific, medical, and technical peer-reviewed scholarly journals that publish nearly 2.5 million articles a year, the equivalent of a manuscript every 13 seconds. Moreover, according to the International Association of Scientific, Technical and Medical Publishers, the number of journals and articles published in those fields has grown by between 3 and 3.5% a year for the past two centuries. A question that may be worth pondering is whether this growth is good or bad. PMID- 27262464 TI - Many College Students Underestimate Diabetes Risk. AB - BACKGROUND: College students form long-lasting diet and health behaviors that are associated with an increased lifetime risk of type 2 diabetes. Thus, colleges and universities can be critical settings to increase awareness of diabetes risk and for nutrition education and health interventions. However, it is not clear if high-risk students recognize the likelihood of diabetes in their future. OBJECTIVE: To assess personal risk perceptions of a sample of multiracial college students with three or more known risk factors for diabetes, and to identity characteristics of students with an unrealistic perception of their future risk. DESIGN: Self-reported data on health and behavior were collected from 1,579 students from three urban colleges. The students at high risk (n=541) for diabetes were categorized as having either a realistic or unrealistic perception of their future risk of diabetes. Characteristics of the two groups were examined using multivariate logistic regression. RESULTS: Approximately 61% of the high risk students recognized they were more likely to develop diabetes than others, while the remaining 39% did not perceive their personal risk to be high. The under-estimators were significantly more likely to be male (p=0.010), have no family history of diabetes (p=0.029), and be born outside the United States (p<0.001). CONCLUSIONS: The under-estimators, an unrealistically optimistic high risk group, warrant attention, as an unrealistic perception may reduce their likelihood of taking preventive actions to diminish the threat. There is a pressing need to heighten knowledge and awareness of diabetes risk and to develop models of health education and behavior change that are both relevant and effective for young adults. PMID- 27262465 TI - Reassessment of Allied Health Professionals' Level of Self-Efficacy in, Outcome Expectancy in, and Use of Evidence-Based Practice. AB - AIM: Evidence-based practice (EBP) is fundamental to improving patient outcomes. Factors affecting EBP capabilities are linked with institutional culture and barriers, personal self-belief, and individual ability. To effect change in capabilities, interventions must target barriers and be informed by behaviour change theory. This study measured the effect of training and organisational change on EBP measures amongst allied health professionals. METHODS: All allied health staff (n=196) employed across the Mater Health Services (Brisbane, Queensland) were invited to complete a survey assessing EBP self-efficacy, outcome expectancy and use, as well as EBP training undertaken. Data were compared with those of surveys from 2010 and 2011. RESULTS: Response rate was 70.9% (n=139/196); 32 staff completed all surveys. Significant improvements were observed in staff undertaking training (EBP, p=0.008; research design and analysis, p=0.003) since the first survey. The significant increase in EBP self efficacy that occurred from T1 to T2 remained at T3 (p=0.008). Fewer between department differences were observed over time. CONCLUSIONS: This study identified sustained EBP self-efficacy improvements in this cohort and found that between-department differences have virtually disappeared. Ongoing interventions are required to sustain and improve staff's belief in their ability to deliver EBP. PMID- 27262462 TI - Genome-wide association of familial prostate cancer cases identifies evidence for a rare segregating haplotype at 8q24.21. AB - Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 (p = 1.7e(-8)) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease (p = 8.5e(-11)). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus. PMID- 27262466 TI - Student Physical Therapists' Competence and Self-Confidence in Basic Clinical Assessment and Musculoskeletal Differential Diagnosis. AB - Student physical therapists are expected to learn and confidently perform technical skills while integrating nontechnical behavioral and cognitive skills in their examinations and interventions. OBJECTIVE: The purpose of this study was to compare the self-confidence of entry-level doctoral student physical therapists during foundational assessment and musculoskeletal differential diagnosis courses and the students' competencies based on skills examinations. DESIGN: Methods using qualitative and quantitative procedures. METHODS: Student physical therapists (n=27) participated in a basic assessment course followed by a musculoskeletal differential diagnosis course. The students completed confidence surveys prior to skills examinations in both courses. A random sample of students participated in focus groups, led by a researcher outside the physical therapy department. RESULTS: Student confidence did not correlate with competency scores. At the end of the basic clinical assessment course and the beginning of the differential diagnosis course, students' confidence was significantly below baseline. However, by the end of the differential diagnosis course, student confidence had returned to original baseline levels. CONCLUSIONS: Over three semesters, the students lost confidence and then regained confidence in their abilities. Additional experience and practice influenced perceived confidence. However, increased competence may have been associated with poor self appraisal skills instead of increased competency. PMID- 27262467 TI - Student Outcomes Associated with an Interprofessional Program Incorporating TeamSTEPPS(r). AB - BACKGROUND: Interprofessional education (IPE) of health professions students is a starting point for developing collaborative-practice-ready healthcare professionals, ultimately leading to improved patient care. The purpose of this study was to develop and evaluate a novel, foundational, IPE pilot program that incorporates TeamSTEPPS(r) for health professions students. METHODS: Students representing 13 different health professions programs participated in successive Level 1 and Level 2 "Foundations of Interprofessional Collaboration: Introduction to TeamSTEPPS(r)" half-day activities (n = 241). Students' satisfaction with the pilot program, changes in attitudes toward teamwork from before to after participation, TeamSTEPPS(r) knowledge acquisition, and anticipated future interprofessional collaboration-oriented behavior change were assessed through online surveys. RESULTS: Overall, students were highly satisfied with the pilot program and reported that learning from other professions was valuable. Statistically significant positive changes were noted in attitudes toward teamwork, most notably with the Level 1 pilot. Greater than 80% of students who completed the surveys demonstrated acquisition of TeamSTEPPS(r) knowledge. Students also reported feeling more prepared to collaborate interprofessionally in their future practice. CONCLUSION: This study demonstrated that the two-level foundational pilot program is feasible and had the intended effects with regards to moving health professions students toward becoming collaborative-practice ready healthcare professionals. PMID- 27262468 TI - Student Reflections on Interprofessional Education: Moving from Concepts to Collaboration. AB - PURPOSE: We analyzed student reflection essays to evaluate the impact of an interprofessional education (IPE) curriculum on what students value and personally learn from their participation. METHODS: After completing a 2-year IPE curriculum in the Health Mentors Program (HMP), while partnered with a mentor with chronic disease(s), 264 students from six health professions submitted personal reflection papers, using the Rolfe Reflection-in-Action model. A sample of 60 essays was analyzed using conventional content analysis guided by grounded theory. RESULTS: Qualitative analysis revealed 15 themes and 14 subthemes in the essays. The themes and subthemes were organized into four main categories: program, mentor, team, and self. Most students viewed the HMP curricular design positively. In particular, they cited the team-based home visit as a critical piece in changing their perceptions of the impact of chronic disease on their health mentor. Mentors' positive attitude and approach toward life also had a profound impact on students. Approximately half of the students identified positive team dynamics as a key component for optimal patient care and better health outcomes, noting improved understanding of team members' professional roles and responsibilities after working together in this longitudinal IPE program. The "self" category had the highest frequency count, with students describing positive changes in self-assessed knowledge, skills, and attitudes. CONCLUSIONS: Our findings suggest that reflective writing is an effective exercise through which students can explore their attitudes toward IPE and team based care of individuals with chronic diseases. After participation in this IPE curriculum, students identified having an improved understanding of collaborative practice goals, indicative of meeting an IPE core competency, and described a new understanding of patient-centeredness. PMID- 27262469 TI - Effectiveness of Clinical Supervision of Allied Health Professionals: A Survey. AB - The practice of clinical supervision (CS) is recommended for allied health professionals. Preliminary evidence suggests that CS can be effective, but it is unknown for which allied health professions it is most effective. METHOD: The effectiveness of CS was measured using the allied health-specific modified Manchester Clinical Supervision Scale (MCSS-26). Subscales of the MCSS-26 were summed for three domain scores (normative, restorative and formative). RESULTS: One hundred ninety-six allied health professionals working in seven disciplines completed the survey. Allied health profession and supervisor experience had a significant effect on total MCSS-26 score (p=0.004 and 0.001, respectively). Allied health professions scored significantly lower in the normative domain than the restorative domain (mean diff 6.0%, 95%CI 3.3 to 8.7, p<0.001) and the formative domain (mean diff 7.9%, 95%CI 5.7 to 10.1, p<0.001). CONCLUSIONS: A significant difference exists between allied health professions in the effectiveness of CS, with social workers, psychologists, and occupational therapists reporting effective supervision, while the effectiveness of CS for physiotherapists, dieticians, podiatrists, and speech-language pathologists was uncertain. All professions reported that CS was least effective in the normative domain, indicating that it was difficult to find time to participate in CS. PMID- 27262470 TI - Perceived Leadership Practices in Year-One Students Enrolled in Professional Entry-Level Doctor of Physical Therapy Programs. AB - BACKGROUND: Leadership has been identified as an important attribute for health care professionals. Assessing leadership practices can help identify areas of strength or needed improvement for the development of leaders. OBJECTIVES: To describe the perceived leadership practices of year-1 Doctor of Physical Therapy (DPT) students, to determine if the participants' demographic variables were related to their perceived leadership practices, and to explore differences between participants and the general population. METHODS: The Leadership Practices Inventory (LPI Self) developed by Kouzes and Posner was used to assess leadership practices of year-1 DPT students at six Midwestern universities. RESULTS: The leadership practices of 192 DPT students in highest to lowest order were Enable, Encourage, Model, Challenge, and Inspire. Age was found to be significantly correlated with the Challenge leadership practice. The order and means of some leadership practices of the DPT students were different than the general population. CONCLUSIONS: This study provides a baseline description of how year-1 DPT students perceived their leadership behaviors and how the LPI Self can be used to facilitate the development of leadership skills. PMID- 27262471 TI - Factors Influencing Texas Physical Therapy Students' Membership in the American Physical Therapy Association and the Texas Physical Therapy Association: Implications for Academicians, Clinicians, and Professional Associations. AB - OBJECTIVE: To determine the factors impacting the decisions of student physical therapists (PTs) and physical therapist assistants (PTAs) to join and maintain membership in the American Physical Therapy Association and the Texas Physical Therapy Association, in light of a membership initiative of Reach 100 that was adopted in Texas. STUDY DESIGN: Survey, descriptive. METHODS: An online membership survey invitation was distributed to Texas PT and PTA students. RESULTS: A total of 479 students responded to the survey. A majority of participants (67%) reported being members, while 33% reported being non-members. The primary reason students (74%) reported for being a member was that they were encouraged by their academic program. Students who are not members (87%) cited the high cost of national dues. A majority of participants (n=379, 83%) rated faculty promotion of membership as somewhat high to high. In contrast, only 26% rated the promotion of membership by their clinical education sites as somewhat high to high. Professional growth and development was cited as the main reason to maintain membership. CONCLUSIONS: Although students are being encouraged to join, a third of the respondents still do not belong. It is imperative that clinical mentors model and support membership activities. Association leadership may use this information to develop strategic plans to be inclusive of the student and new professional. PMID- 27262472 TI - Comparison of Teaching Strategies for Cultural Humility in Physical Therapy. AB - Cultural competence and cultural humility are ongoing processes that healthcare professionals should continually strive for in order to provide effective and comprehensive plans of care for patients. METHODS: This 2-year, longitudinal, educational pilot study describes the levels of competency in second-year entry level physical therapy students and compares the outcomes of three teaching strategies for cultural competence and cultural humility. All students received a standard 2-hour lecture; study volunteers were randomly assigned to one of two enriched educational groups, involving a standardized patient or a paper case enrichment. RESULTS: Students shifted from initial levels of "culturally incompetent" and/or "culturally aware" to "culturally competent" as measured by the Inventory for Assessing the Process of Cultural Competence Among Healthcare Professionals-Revised. This shift was maintained after 1.5 yrs following the exposure. Because the enriched educational groups were underpowered, preliminary quantitative data are inconclusive, but qualitative feedback from students is strongly positive. DISCUSSION: A minimal dose of a structured 2-hr lecture with a skilled instructor, who creates a safe environment for cultural learning, produced positive shifts toward greater cultural competence. Five processes emerged for teaching cultural humility that may assist in designing comprehensive educational experiences on this topic. A framework for organizing course content is presented. PMID- 27262473 TI - Teaching Collaboration Competencies to Healthcare Provider Students Through Simulation. AB - PURPOSE: Although interprofessional collaboration has been proven to reduce the number of errors, few programs have incorporated interprofessional training into their programs. The purpose of this study was to determine if attitudes and observed collaborative behaviors among an interprofessional group of students improved or increased following an intervention that included a didactic session on the process of collaboration, a low-fidelity simulation of interprofessional patient care rounds, and facilitated debriefing sessions. METHODS: In this mixed methods study, two scales from the TeamSTEPPSTM Teamwork Attitudes Questionnaire (TAQ) were used as a pre- and post-test to assess attitude and behavior changes in students. Qualitative data were also collected via semi-structured interviewing and observation. RESULTS: Students (n=515) from eight professional healthcare programs participated in the study. Statistical significance (p<0.001) was reached in 10 of the 12 TAQ questions, indicating that attitudes towards teamwork and collaboration improved substantially. All observed collaborative behaviors increased between 3 to 18% pre- to posttest. Students reported that the intervention taught them about other provider roles and gave them the language they needed to collaborate. CONCLUSIONS: Low-fidelity scripted simulation of patient care rounds is a cost-effective and time-efficient method to teach interprofessional collaboration simultaneously to large groups of students in diverse healthcare professional programs. PMID- 27262474 TI - Examining the Phenomenon of the Administrative Burden in Health Care, Allied Health, and Respiratory Care. AB - Documentation expectations for allied health professional appears to have changed dramatically in the past decade. The purpose of this essay is to discuss the literature related to clinician perceptions of these documentation expectations and changes in the workload attributable to such administrative duties, review the results of a recent pilot project surveying respiratory therapists' perception of documentation, and reflect upon the potential ramifications of excessive documentation. This commentary also discusses some recommendations for the future in terms of the design of documentation systems and the need for additional research to further explore this area. PMID- 27262475 TI - Students' Readiness and Perception of Interprofessional Learning in an Undergraduate Swiss Healthcare Student Context: A Cross Sectional Study. AB - PURPOSE: The objective of this study was to assess attitudes toward interprofessional education (IPE) among undergraduate health students in Switzerland after 2 weeks of IPE training during the first year of their bachelor's curriculum. METHODS: A cross-sectional study using a convenience sample of first-year undergraduate healthcare students assessed using the RIPLS scale. RESULTS: A total of 140 students participated in this study. Physiotherapist students achieved the highest mean scores for the total RIPLS. However, the total mean score for RIPLS for nurse students was statistically lower (p<0.001) in comparison to the other departments. CONCLUSIONS: The findings are inspiring in that students demonstrated positive attitudes, perceptions, and attributes toward IPE activities. This study contributes to the development of innovative IPE activities. PMID- 27262476 TI - Academicians and Neurologic Physical Therapy Residents Partner to Expand Clinical Reflection Using the SOLO Taxonomy: A Novel Approach. AB - Creating curriculums that develop physical therapy (PT) students into evidenced based, critically reflective, entry-level practitioners is one of the primary goals for PT programs. Academic faculty partnering with neurologic residency programs to design learning environments that capitalize upon the strengths of both can create insightful educational experiences for students during their didactic training. These partnerships support the development of critical thinking skills and provide mentorship for residents transitioning from their role as a clinician to that of an educator. Using the SOLO (structure of observed learning outcomes) taxonomy as a framework for developing learning experiences, Seton Hall University neurologic academic faculty and program directors from the Kessler Institute for Rehabilitation Residency in Neurologic Physical Therapy have built a partnership that seeks to develop critical reflection skills in both the neurologic resident and entry-level PT students. While integration of residents into entry-level PT curriculum may not be novel, we believe that utilizing the SOLO model within this partnership is unique. This paper describes the partnership and learning experiences rooted in the SOLO taxonomy theoretical framework and discusses perceived benefits of this learning experience across professional health science programs. PMID- 27262477 TI - An Innovative Program in the Science of Health Care Delivery: Workforce Diversity in the Business of Health. AB - According to the most recent statistics from the National Center for Education Statistics, disparities in enrollment in undergraduate and graduate education are significant and not improving commensurate with the national population. Similarly, only 12% of graduating medical students and 13% of graduating physician assistant students are from underrepresented racial and ethnic groups. Established in 2012 to promote health care transformation at the organization and system levels, the School for the Science of Health Care Delivery is aligned with the university and college missions to create innovative, interdisciplinary curricula that meet the needs of our diverse patient and community populations. Three-year enrollment trends in the program exceed most national benchmarks, particularly among students who identify as Hispanic and American Indian/Alaska Native. The Science of Health Care Delivery program provides students a seamless learning experience that prepares them to be solutions-oriented leaders proficient in the business of health care, change management, innovation, and data-driven decision making. Defined as the study and design of systems, processes, leadership and management used to optimize health care delivery and health for all, the Science of Health Care Delivery will prepare the next generation of creative, diverse, pioneering leaders in health care. PMID- 27262478 TI - Perceptions of Graduating Health Professional Students of Their Interprofessional Education Experiences during Pre-Licensure Education. AB - The purpose of this qualitative descriptive study was to identify graduating students' perspectives on what makes prelicensure interprofessional education (IPE) and interprofessional collaboration (IPC) experiences valuable and effective and to identify other opportunities for effective IPE. We conducted telephone interviews with 12 students in medicine, nursing, pharmacy, and physiotherapy during their final year of training and thematically analyzed the verbatim transcripts. We found factors that make existing IPE experiences valuable and effective and could facilitate leverage of other curricular opportunities include: 1) experiential learning in clinical and classroom contexts, 2) relevancy of the IPE experiences, 3) opportunities for role clarification, 4) supervisors' influence (e.g., modeling collaborative skills), and 5) integration of IPE and IPC experiences into the existing curriculum. PMID- 27262479 TI - Quality improvement program reduces venous thromboembolism in infants and children with long-gap esophageal atresia (LGEA). AB - PURPOSE: Patients with long-gap esophageal atresia (LGEA) treated with the Foker process are at increased risk of venous thromboembolism (VTE). An institutional quality improvement program to decrease VTE risk factor exposure and utilize prophylactic anticoagulation was implemented. We aim to evaluate the efficacy and safety of a VTE risk-reduction program in patients with LGEA. METHODS: Implementation and evaluation of a VTE risk-reduction program in patients with LGEA from 2012 to 2015 was performed. Symptomatic VTE with radiographic confirmation were defined as events. Post-program characteristics were evaluated and compared to a historical cohort. RESULTS: Sixty-seven patients were identified. Two developed VTE (7 %) post-program implementation; compared to 13/40 (33 %) VTE incidence in the historical cohort (p = 0.018). Baseline demographics were similar, including age, esophageal atresia type and gap length. Post-protocol patients had fewer paralysis episodes (p = 0.004), paralysis days (p = 0.003), central venous catheters (p = 0.003), thoracotomies (p < 0.001), ventilator hours (p = 0.02), and decreased hospital (p < 0.001) and ICU stay (p < 0.001). All patients in the VTE risk-reduction program were exposed to prophylactic anticoagulation. No bleeding complications and/or thrombosis-related mortality occurred. CONCLUSION: VTE risk-reduction program implementation decreased symptomatic VTE incidence with associated decreases in ICU and hospital length of stay. Prophylactic anticoagulation can be utilized safely in a complicated pediatric surgical population. PMID- 27262480 TI - Validation and comparison of the psychometric properties of the EQ-5D-3L and EQ 5D-5L instruments in Greece. AB - PURPOSE: To validate and compare the psychometric properties of the EQ-5D-3L with the EQ-5D-5L classification systems in Greece. METHODS: Participants (n = 2279) over 40 years old, sampled from the greater area of Athens using a multistage stratified quota sampling method, completed both EQ-5D versions, while information was also collected on socio-demographics and health-related characteristics. The EQ-5D-5L and EQ-5D-3L were evaluated in terms of agreement, ceiling effects, redistribution and inconsistency, informativity, and convergent and known-groups validity. RESULTS: The agreement between the EQ-5D-3L and EQ-5D 5L was high (ICC = 0.85). Ceiling effects decreased significantly in the EQ-5D-5L in all domains (P < 0.001), with "usual activities" (-21.4 %) and "self-care" ( 20.1 %) showing the highest absolute and "anxiety/depression" the highest relative reduction (-32.46 %). Inconsistency was low (5.7 %). The increase in prevalence of problems was larger than the decrease in their severity, resulting in a lower mean health utility for the EQ-5D-5L. Overall absolute and relative informativity improved by 70.5 % and 16.4 %, respectively, in the EQ-5D-5L. Both instruments exhibited good convergent and known-groups validity, with evidence of a considerably better convergent performance and discriminatory ability of the EQ 5D-5L. CONCLUSIONS: Both EQ-5D versions demonstrated good construct validity and had consistent redistribution. The EQ-5D-5L system may be preferable to the EQ-5D 3L, as it exhibited superior performance in terms of lower ceiling effects, higher absolute and relative informativity, and improved convergent and known groups validity efficiency. PMID- 27262481 TI - Estimating the postmortem interval of human skeletal remains by analyzing their optical behavior. AB - The aim of this study was to figure out a new practically applicable method to distinguish between historical and recent human skeletal remains. Therefore, the optical behavior of bone cross sections was investigated using the combination of two methods: a modification of an already established test (UV-induced fluorescence) and a new method (490 nm-induced fluorescence). We evaluated the areal extent of fluorescence of 30 bone cross sections with known postmortem interval (PMI) using ultraviolet light and 490 nm light. For analysis, the areal extend of fluorescent surface was determined using photos of the samples and an image editing software. The results prove that there is a correlation between PMI and the areal extent of fluorescent surface in both tests. Furthermore, the combination of both methods is a good indicator to distinguish within the forensic relevant post mortem interval between PMI < 30 years and PMI > 30 years. PMID- 27262482 TI - Blood identification and discrimination between human and nonhuman blood using portable Raman spectroscopy. AB - Raman spectroscopy is commonly used in chemistry to identify molecular structure. This technique is a nondestructive analysis and needs no sample preparation. Recently, Raman spectroscopy has been shown to be effective as a multipurpose analytical method for forensic applications. In the present study, blood identification and discrimination between human and nonhuman blood were performed by a portable Raman spectrometer, which can be used at a crime scene. To identify the blood and to discriminate between human and nonhuman blood, Raman spectra of bloodstains from 11 species (human, rat, mouse, cow, horse, sheep, pig, rabbit, cat, dog, and chicken) were taken using a portable Raman spectrometer. Raman peaks for blood (742, 1001, 1123, 1247, 1341, 1368, 1446, 1576, and 1619 cm-1) could be observed by the portable Raman spectrometer in all 11 species, and the human bloodstain could be distinguished from the nonhuman ones by using a principal component analysis. This analysis can be performed on a bloodstain sample of at least 3 months old. The portable Raman spectrometer can be used at a crime scene, and this analysis is useful for forensic examination. PMID- 27262483 TI - Expelled uninsured patients in a less-competitive hospital market in Florida, USA. AB - BACKGROUND: This research evaluates the effect of hospital competition on inward and outward patient transfers for different types of payers including the uninsured. Although it is a less spotlighted issue, an equally important topic is the likelihood of inter-hospital patient transfers of the insured and the uninsured. This study attempts to fill a gap in the research about the relationship between hospital competition and patient transfers. METHODS: By developing the payer-specific level of hospital competition, this research evaluates the effect of hospital competition on inward and outward patient sharing (or patient transfers) for different types of payers including the uninsured. For patient transfers, instead of focusing on whether a patient is transferred from one hospital to another hospital at the patient level, we measure the numbers of patient transfers between hospitals (both inward and outward) at the hospital level. These dependent variables-the numbers of outward and inward patient transfers by the principal payers-are count variables, and we employ either a Poisson regression model or a negative binomial regression model. RESULTS: Controlling for hospital characteristics, when the uninsured Hirschman Herfindahl Index (HHI) increased by 0.01, the uninsured were 593 % more likely to be transferred to another hospital. When a hospital dominates its market, it tends to expel uninsured patients to other hospitals. CONCLUSION: If patient transfers are medically unnecessary and primarily due to financial incentives, health administrators and policymakers should minimize such events. Since the uninsured who are admitted to a hospital that dominates its hospital market are likely to be much more vulnerable in their access to health care services, the state government of Florida needs to move toward increased health insurance coverage for eligible Floridians. PMID- 27262485 TI - Bioinspired Platform Conjugated Active Drug Delivery. AB - BACKGROUND: The rapid emergence of nanotechnology and biotechnology has enabled revolutionary developments for drug delivery systems. Recently, drug delivery has attracted extensive research interest; applied to improve the functions of these carriers and their applications. OBJECTIVE: Active drug delivery is currently approved as an ideal approach for targeted transport in a biological entity and can cooperate with therapeutic mediums in transporting cargoes. RESULTS AND CONCLUSION: In this review, several active targeted cargomediated drug delivery patterns have been summarized, including molecular motors, bio-camouflaged particles, and self-propelled nanomotors. Subsequently, a series of active targeted carriers for drug delivery were introduced, and their ability for targeted binding was discussed. Furthermore, the mechanism of active targeted transport was exposited in detail, and some promising works are highlighted. PMID- 27262484 TI - Proteomic and peptidomic differences and similarities between four muscle types from New Zealand raised Angus steers. AB - Four muscles from New Zealand-raised Angus steers were evaluated (musculus semitendinosus, m. longissimus thoracis et lumborum, m. psoas major and m. infraspinatus) to test their differences and common features in protein and peptide abundances. The ultimate goal of such a comparison is to match muscle types to products with targeted properties. Protein profiling based on two dimensional electrophoresis showed that the overall profiles were similar, but, between muscle types, significant (p<0.05) intensity differences were observed in twenty four protein spots. Profiling of endogenous peptides allowed characterisation of 346 peptides. Quantitative analysis showed a clear distinction between the muscle types. Forty-four peptides were identified that showed a statistically significant (p<0.05) and substantial (>2-fold change) difference between at least two muscle types. These analyses demonstrate substantial similarities between these four muscle types, but also clear distinctions in their profiles; specifically a 25% difference between at least two muscles at the peptidomic level, and a 14% difference at the proteomic level. PMID- 27262486 TI - Recent Advances in pH-Sensitive Polymeric Nanoparticles for Smart Drug Delivery in Cancer Therapy. AB - BACKGROUND: Rapid developments in the field of nanoparticles during the last decades have led to its increased application in drug delivery approaches. The advantages of nano-based drug delivery systems include improved therapeutic efficacy of drugs and the reduction of side effects. OBJECTIVE: This review aims to highlight advances in stimuli-triggered drug delivery approaches using polymeric nanoparticles with a focus on pH-sensitive drug- and theranostic delivery systems. RESULTS AND CONCLUSION: Of the various organic/inorganic nanoparticles, polymeric nanoparticles have fulfilled an integral role in the advancement of drug delivery systems by virtue of the ease to incorporate and modify targeting moieties in combination with controlled drug release over prolonged periods. Furthermore, polymeric nanoparticles facilitate theranostic treatment by the incorporation of imaging agents in addition to therapeutics. Recently, stimuli-responsive polymeric nanoparticles emerged as smart drug carriers, in which drug release is affected by physical and/or chemical structural changes induced by a specific stimulus (e.g. pH, temperature, and specific enzymes). The use of these nanocomposites reduces premature drug release and maintains effective drug levels at the pathological target. PMID- 27262488 TI - Targeted Mesoporous Silica Nanocarriers in Oncology. AB - BACKGROUND: Cancer is one of the major leading causes of death worldwide and its prevalence will be higher in the coming years due to the progressive aging of the population. The development of nanocarriers in oncology has provided a new hope in the fight against this terrible disease. OBJECTIVE: Among the different types of nanoparticles which have been reported in the scientific literature, mesoporous silica nanoparticles (MSNs) are very promising materials due to their inherent properties such as high loading capacity of many different drugs, excellent biocompatibility and easy functionalization. RESULTS: This review presents the current state of the art related to the development of mesoporous silica nanocarriers for antitumoral therapy paying special attention on targeted MSN able to selectively destroy tumoral cells, reducing the side damage in healthy ones, and the basic principles of targeting tumoral tissues and cells. CONCLUSIONS: MSNs constitute a promising nanomaterial for drug delivery applications in antitumoral therapy as a consequence of its unique properties such as excellent biocompatibility, high loading capacity, robustness, easy production and existence of multiple strategies for their functionalization with a myriad of bio-organic moieties. In the coming years, the clever application of this material would provide novel alternatives for the treatment of this complex disease. PMID- 27262489 TI - The variability of corneal and anterior segment parameters in keratoconus. AB - PURPOSE: To analyse, describe and test diverse corneal and anterior segment parameters in normal and keratoconic eyes to better understand the geometry of the keratoconic cornea. METHOD: 44 eyes from 44 keratoconic patients and 44 eyes from 44 healthy patients were included in the study. The Pentacam System was used for the analysis of the anterior segment parameters. New ad-hoc parameters were defined by measuring the distances on the Scheimpflug image at the horizontal diameter, with chamber depth now comprising of two distinctive distances: corneal sagittal depth and the distance from the endpoint of this segment to the anterior surface of the lens (DL). RESULTS: Statistically significant differences (p<0.05) between normal and keratoconic eyes were found in all of the analysed corneal parameters. Anterior chamber depth presented statistical differences between normal and keratoconic eyes (3.06+/-0.43mm versus 3.34+/-0.45mm, respectively; p=0.004). This difference was found to originate in an increase of the DL distance (0.40+/-0.33mm in normal eyes against 0.61+/-0.45mm in keratoconic eyes; p=0.014), rather than in the changes in corneal sagittal depth. CONCLUSION: These findings indicate that keratoconus results in central and peripheral corneal manifestations, as well as changes in the shape of the scleral limbus. The DL parameter was useful in describing the forward elongation and advance of the scleral tissue in keratoconic eyes. This finding may help in the monitoring of disease progression and contact lens design and fitting. PMID- 27262490 TI - Infective Endocarditis due to Listeria Monocytogenes: A Report of 4 Patients. PMID- 27262491 TI - Immunohistochemical differentiation of eosinophilic esophageal myositis from eosinophilic esophagitis. AB - BACKGROUND AND AIM: Eosinophilic esophagitis (EoE) is a Th2-mediated allergic disease of the esophageal epithelium, associated with antigen. We previously reported a case series for eosinophilic esophageal myositis (EoEM)-a novel eosinophilic gastrointestinal disorder defined as eosinophilic infiltration localized in the esophageal muscle layer-and diagnosed it by peroral endoscopic muscle biopsy. Here, we investigated the immunopathology of EoEM to differentiate it from EoE. METHODS: Histological analysis was performed for three cases of EoEM and EoE, respectively. The results were compared with those of two control samples (non-eosinophilic gastrointestinal disorder full-layer esophagus). Using immunofluorescence, we analyzed the expression of the chemokine receptor CCR3 and its ligands eotaxin-1 and eotaxin-3 to investigate the eosinophilic reaction. Additionally, we determined the expression patterns of desmoglein-1 in the esophageal epithelium, which shows dysregulated expression in EoE. RESULTS: Eosinophil infiltration was observed in the muscle layer (maximum number, 30, 36, 73/high-power field) and the epithelium (50, 44, 40/high-power field) for EoEM and EoE, respectively. In EoE esophageal epithelium, the number of eotaxin-3 positive epithelial cells was significantly increased together with CCR3-positive infiltrating cells. However, in EoEM, a number of eotaxin-1-positive and eotaxin 3-positive myocytes and vascular endothelial cells were increased in the esophageal muscle layer. A significant loss of desmoglein-1 expression was only observed in EoE, not in EoEM. CONCLUSIONS: Eotaxin-1 and eotaxin-3 expression on the smooth muscle and vessels plays a role in the pathogenesis of EoEM, while EoE shows an epithelial eotaxin-3-dominant immunoreaction. Thus, the EoEM immunological pattern displays clear differences from that of EoE. PMID- 27262492 TI - Down-regulation of let-7a-5p predicts lymph node metastasis and prognosis in colorectal cancer: Implications for chemotherapy. AB - Colorectal cancer (CRC) guidelines recommend adjuvant chemotherapy according to the level of lymph node metastasis. Let-7a-5p is a microRNA, which inhibits migration, invasion, as well as the epithelial-mesenchymal transition by targeting HMGA2. The aim of this study was to investigate the role of let-7a-5p in the clinical impact of CRC. In this study, one hundred and ninety-two CRC patients were enrolled. The expression of let-7a-5p and HMGA2 in serum and tumour tissues were analysed by real-time PCR and immunohistochemistry. Kaplan-Meier analysis was used to analyse primary outcomes, including the survival and tumour recurrence. The expression of let-7a-5p in tumour tissues was significantly negative correlated with the tumour size, stage and lymph node metastasis in CRC patients (p = 0.024 for tumour size, p < 0.0001 for stage and p < 0.0001 for lymph node metastasis). There was a negative correlation between the levels of let-7a-5p and the HMGA2 protein (p < 0.0001). The overall survival (OS) and disease-free survival (DFS) rates of patients with let-7a-5p low/HMGA2 high were poorer than those with let-7a-5p high/HMGA2 high, let-7a-5p high/HMGA2 low and let-7a-5p low/HMGA2 low. In addition, the expression levels of let-7a-5p in serums were positively correlated with let-7a-5p in the tumour tissues of the CRC patients. The expression levels of let-7a-5p in serums also could be used as a biomarker to predict clinical outcome. We suggest that down-regulation of let-7a 5p in serums and tumour tissues of CRC patients could be used to predict lymph node metastasis and the disease prognosis. These results could be implicated for chemotherapy suggestion. PMID- 27262493 TI - Letter-to-the-Editor "Laparoscopic treatment of early-stage endometrial cancer with and without uterine manipulator: Our experience and review of literature" by Tinelli R et al. (Surgical Oncology 25 (2016) 98-103). PMID- 27262494 TI - Sarcopenia in Elderly Diabetic Patients: Role of Dipeptidyl Peptidase 4 Inhibitors. AB - BACKGROUND: Our study aimed to investigate the effect of dipeptidyl peptidase 4 inhibitors (DPP4-I) on sarcopenic parameters in elderly type 2 diabetic patients. DESIGN: All elderly diabetic patients were invited to present themselves at our outpatient Geriatric Centre to undergo to evaluation of glycemic, inflammatory, and sarcopenic parameters and to perform a meal test for glucagon-like peptide-1 analogue (GLP-1) activity evaluation. SETTING: According to European Working Group on Sarcopenia in Older People (EWGSOP) criteria, sarcopenic parameters were assessed by bioelectrical impedance analysis (BIA) and Kern dynamometer and 4-m gait speed tests. All patients received standardized meals for the assessment of postprandial levels of GLP-1 activity. PARTICIPANTS, MEASUREMENTS: Data of 80 elderly diabetic patients treated with oral glucose-lowering drugs (DPP4-I or Sulfonylureas Group) for at least 24 months before enrollment were analyzed. RESULTS: The DPP4-I Group showed appropriate glycemic control, lower levels of inflammatory parameters, a significant and greater increase, during interprandial periods, of GLP-1 activity, and better sarcopenic parameters (fat-free mass, skeletal muscle mass, and related indices, muscle strength, and gait speed) compared with the Sulfonylureas Group. Univariate analysis showed that sarcopenic parameters correlated with glycemic control and with GLP-1 area under the curve values. Multivariate analysis confirms these relationships. CONCLUSION: The results are consistent with the hypothesis that DPP4-I use might have a positive effect on the loss of muscle mass and its function. PMID- 27262495 TI - Macular thickness and volume in the elderly: A systematic review. AB - Ageing leads to a number of changes in the body including the macula. Detailed imaging using optical coherence tomography have enabled in vivo studies of how macula changes with age. Here we systematically review 49 studies (9115 participants and 11,577 eyes) to provide an overview of how ageing manifests in the macula of the elderly focusing on clinical relevant measures that are thicknesses and volumes of different macular areas. Ageing seems to increase center point foveal thickness. Ageing does not seem to change the center subfield thickness significantly. Ageing decreases the inner and outer macular thickness, and the overall macular thickness and volume. Studies find that specific retinal layers at specific locations seem to be the contributor to these changes. These findings confirm that age-related changes suggested in histological studies are measurable in vivo on thickness and volume and differ depending on location. Studies are needed to explore reasons for the large variance in measurements and how ageing by itself contributes to development of macular disease. PMID- 27262496 TI - Toxicity of an herbicide and adjuvant to saltmarsh invertebrates in the management of invasive grass; Comparative laboratory and field tests. AB - Coastal weeds are often treated with herbicides without knowledge of non-target impacts, and toxicity data from standardized test species can have limited applicability. We evaluated toxicity to invertebrates from Fusilade Forte(r) and the adjuvant Hasten(r) in the control of invasive salt marsh grass, Spartina anglica. For 3 of 4 local invertebrates, Fusilade Forte(r) was moderately toxic (96h LC50 5.4-144mgL(-1)), whereas Hasten(r) was less toxic (14.2-450mgL(-1)). For most species, the mixture was more toxic than the herbicide alone, with 96h LC50 reduced 23-45%. However, a field experiment applying typical concentrations (1000*the lowest 96h LC50) showed low concentrations of herbicide residues and no detrimental impacts on invertebrates over 6months. The results reveal the importance of testing locally relevant species for potential toxicity, and of comparison tests with field exposures to determine the realised toxicity in nature. PMID- 27262497 TI - Responses of bacterial and archaeal communities to nitrate stimulation after oil pollution in mangrove sediment revealed by Illumina sequencing. AB - This study aimed to investigate microbial responses to nitrate stimulation in oiled mangrove mesocosm. Both supplementary oil and nitrate changed the water and sediment chemical properties contributing to the shift of microbial communities. Denitrifying genes nirS and nirK were increased several times by the interaction of oil spiking and nitrate addition. Bacterial chao1 was reduced by oil spiking and further by nitrate stimulation, whereas archaeal chao1 was only inhibited by oil pollution on early time. Sampling depth explained most of variation and significantly impacted bacterial and archaeal communities, while oil pollution only significantly impacted bacterial communities (p<0.05). Despite explaining less variation, nitrate addition coupled with oil spiking enhanced the growth of hydrocarbon degraders in mangrove. The findings demonstrate the impacts of environmental factors and their interactions in shaping microbial communities during nitrate stimulation. Our study suggests introducing genera Desulfotignum and Marinobacter into oiled mangrove for bioaugmentation. PMID- 27262498 TI - Temporal and spatial changes in persistent organic pollutants in Vietnamese coastal waters detected from plastic resin pellets. AB - Plastic resin pellets collected at Minh Chau island and Ba Lat estuary between 2007 and 2014 in Vietnam were analyzed for dichloro-diphenyl-trichloroethanes (DDTs), polychlorinated biphenyls (PCBs) and hexachlorocyclohexanes (HCHs). The study was carried out as part of the International Pellet Watch program for monitoring the global distribution of persistent organic pollutants (POPs). Higher levels of DDTs compared to PCBs indicated agricultural inputs rather than industrial discharges in the region. Most POP concentrations on both beaches decreased over the period, with the exception of HCH isomers. Though the concentration of DDTs showed a drastic decline on both beaches between 2007/2008 and 2014, DDTs accounted for 60-80% of total DDTs, suggesting that there is still a fresh input of these chemicals in the region. This study strongly recommends further investigations to track temporal and spatial patterns of POP levels in the marine environment using plastic resin pellets. PMID- 27262499 TI - Date-prints on stranded macroplastics: Inferring the timing and extent of overwash deposition on the Skallingen peninsula, Denmark. AB - The presented study shows that the delivery of marine macrodebris to a high energy coastal environment has been abundant enough over the last three decades as to allow a spatial reconstruction of morphological change based on production date prints. A dataset of >110 spatially discrete samples has been collected in an area affected by overwashing on the Skallingen peninsula, SW Denmark. A conceptual model for the chronological interpretation of the date prints is proposed and cross-compared with a dense time-series of satellite images and orthophotos. It appears that the litter-derived ages are capable of reproducing information on both the timing and the extent of overwash occurrence. Despite the usefulness of the method as a tool for rapidly assessing the approximate age of recent coastal deposits, the study shows the alarming degree and long-standing of marine-litter pollution on the eastern board of the southern North Sea. PMID- 27262500 TI - Risk of peripartum hysterectomy in births after assisted reproductive technology. AB - OBJECTIVE: To investigate whether women who conceive after assisted reproductive technology (ART) are at higher risk for emergency peripartum hysterectomy. DESIGN: A case-control study using a prospectively maintained institutional database. SETTING: A tertiary referral university teaching maternity hospital. PATIENT(S): Thirty-one women who underwent peripartum hysterectomy for management of hemorrhage, and 19,902 control women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Association between potential predictors and peripartum hysterectomy. RESULT(S): The incidence of peripartum hysterectomy was 1.7 cases per 1,000 births (95% confidence interval [CI] 1.2-2.4). After adjustment for maternal age and twin pregnancy, placenta previa (odds ratio [OR] 50.78, 95% CI 23.30-110.68), prior cesarean delivery (OR 6.72, 95% CI 2.99-15.09 for one cesarean; OR 6.80, 95% CI 1.45-31.90 for two or more cesareans), previous myomectomy (OR 24.59, 95% CI 6.70-90.19), and ART conception (OR 5.98, 95% CI 2.18-16.40) were all antenatal predictors for peripartum hysterectomy. In women having a peripartum hysterectomy, 13.4% of the risk is attributable to mode of conception. CONCLUSION(S): A history of ART increases the likelihood of needing a peripartum hysterectomy to control hemorrhage. Further investigation is needed to determine whether ART conception should be included in algorithms of risk stratification for emergency cesarean hysterectomy and plan of care be modified accordingly. PMID- 27262501 TI - Freeze-all, oocyte vitrification, or fresh embryo transfer? Lessons from an egg sharing donation program. AB - OBJECTIVE: To compare the outcomes of ETs using cryopreserved embryos, cryopreserved oocytes, or fresh embryos. DESIGN: Observational, cohort study. SETTING: Private university-affiliated fertility center. PATIENT(S): This study included 8,210 mature oocytes obtained from 425 oocyte donors. Of those, 5,440 were used for the donors' own cycles (Fresh Oocyte Cycles Group), and 2,770 were cryobanked for 425 recipients (Banked Donor Egg Group). All of the oocytes were sperm injected, resulting in 4,585 embryos from the donors' own cycles and 2,128 embryos from the recipients' cycles. For the donor cycles, embryos were either cryopreserved and transferred during a subsequent cycle (Thaw Cycles Group, 3,209 embryos), or they were transferred during a fresh cycle (Fresh Cycles Group, 1,307 embryos). For the recipient cycles, embryos derived from vitrified oocytes were transferred (Vitrified Oocytes Group, n = 425 cycles, 2,128 embryos). INTERVENTION(S): Oocyte/embryo vitrification and intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Embryo quality, pregnancy, and implantation rates. RESULT(S): Decreased embryo quality and lower rates of blastocyst formation were observed among embryos derived from vitrified oocytes. The highest pregnancy and implantation rates were noted for the Thaw Cycles Group, followed by the Banked Donor Egg Group; the Fresh Cycles Group had the lowest rates. CONCLUSION(S): Oocyte vitrification followed by intracytoplasmic sperm injection leads to lower embryo developmental competence compared with when fresh insemination methods are used. However, pregnancy and implantation rates are higher when embryos are transferred into a "more receptive" endometrium, free of the adverse effects of gonadotropin. Moreover, the freeze-all method leads to exceptional clinical outcomes. PMID- 27262502 TI - Corrigendum to "Mangiferin corrects the imbalance of Th17/Treg cells in mice with TNBS-induced colitis" [Int. Immunopharmacol. (2016) 220-228]. PMID- 27262503 TI - Anaemia, Serum Iron Concentrations and delta-Aminolevulinate Dehydratase Activity in Laying Hens Infected Naturally by Salmonella Gallinarum. AB - The aim of this study was to evaluate anaemia, serum iron concentrations and delta-aminolevulinate dehydratase (ALA-D) activity in laying hens infected naturally by Salmonella Gallinarum and having severe hepatic lesions. Liver and serum samples were collected from 27 laying hens (20 infected and seven uninfected). The delta-ALA-D activity, haematocrit and serum iron concentrations were evaluated. There were significant decreases in delta-ALA-D activity, haematocrit and serum iron concentrations (P <0.01) in birds infected by S. Gallinarum when compared with uninfected birds. There was a positive correlation (P <0.001) between serum iron concentration, haematocrit (r(2) = 0.82) and delta ALA-D activity (r(2) = 0.75). A positive correlation was also observed between delta-ALA-D activity and haematocrit (r(2) = 0.78; P <0.01). Liver samples showed moderate focal coagulative necrosis associated with infiltration of lymphoplasmacytic cells, macrophages and heterophils. The anaemia in the infected hens may be related to reduction in delta-ALA-D activity and serum iron concentrations, since both are important for haemopoiesis. PMID- 27262504 TI - Targeted genome editing in the rare actinomycete Actinoplanes sp. SE50/110 by using the CRISPR/Cas9 System. AB - The application of genome editing technologies, like CRISPR/Cas9 for industrially relevant microorganisms, is becoming increasingly important. Compared to other methods of genetic engineering the decisive factor is that CRISPR/Cas9 is relatively easy to apply and thus time and effort can be significantly reduced in organisms, which are otherwise genetically difficult to access. Because of its many advantages and opportunities, we adopted the CRISPR/Cas9 technology for Actinoplanes sp. SE50/110, the producer of the diabetes type II drug acarbose. The functionality of genome editing was successfully shown by the scarless and antibiotic marker-free deletion of the gene encoding the tyrosinase MelC, which catalyzes the formation of the dark pigment eumelanin in the wild type strain. The generated DeltamelC2 mutant of Actinoplanes sp. SE50/110 no longer produces this pigment and therefore the supernatant does not darken. Furthermore, it was shown that the plasmid containing the gene for the Cas9 protein was removed by increasing the temperature due to its temperature-sensitive replication. The precision of the intended mutation was proven and possible off-target effects caused by the genome editing system were ruled out by genome sequencing of several mutants. PMID- 27262505 TI - Acute Physical Stress Increases Serum Levels of Specific microRNAs. AB - INTRODUCTION: MicroRNA (miR) is non-coding small RNA that regulate mRNA at the post-transcriptional level by degradation or inhibition. To find physical stress markers, we developed a rat model involving a simple and complicated stress and measured serum miR levels. MATERIALS AND METHODS: To demonstrate changes in serum miR levels when physical stress is applied, we constructed three stress modalities using rats: alcohol intake, treadmill running and restraint. After alcohol administration, the rats were made to run on a treadmill and some of the rats were further stressed by restraining with a 2 kg water bag immediately after the treadmill run. The rats were grouped as follows: control, run for 20 min, run for 90 min, run and restrained for 20 min, run and restrained for 90 min. Using total RNA extracted from sera, expression levels of eight miRs were measured by real-time PCR. RESULTS: The level of miR-199a was increased by 20 min stress procedures and the levels of miR-1, miR-24a and miR-133a/b were increased by 90 min stress procedures. No change in the levels of miR-208, miR-212 or miR-296-5p was seen under any stress conditions. There was no significant difference between a treadmill run only and a combination of treadmill run and being restrained by a 2 kg water bag. DISCUSSION: We demonstrated that a combination of these serum miRs might indicate the intensity of stress experienced. PMID- 27262506 TI - Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE2 pathways in human M4Beu melanoma cancer cells. AB - Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (UA), a natural pentacyclic triterpenoid compound. We had demonstrated that tyrosinase and TRP-1 up-regulation in apoptotic cells and the subsequent production of melanin were implicated in an apoptosis resistance mechanism. Several resistance mechanisms to apoptosis have been characterized in melanoma such as hyperactivation of DNA repair mechanisms, drug efflux systems, and reinforcement of survival signals (PI3K/Akt, NF-kappaB and Raf/MAPK pathways). Otherwise, other mechanisms of apoptosis resistance involving different proteins, such as cyclooxygenase-2 (COX-2), have been described in many cancer types. By using a strategy of specific inhibition of each ways, we suggested that there was an interaction between melanogenesis and COX-2/PGE2 pathway. This was characterized by analyzing the COX-2 expression and activity, the expression of tyrosinase and melanin production. Furthermore, we showed that anti-proliferative and proapoptotic effects of UA were mediated through modulation of multiple signaling pathways including Akt and ERK-1/2 proteins. Our study not only uncovers underlying molecular mechanisms of UA action in human melanoma cancer cells but also suggest its great potential as an adjuvant in treatment and cancer prevention. PMID- 27262507 TI - Divided Infringement in the Limelight of the Patent Battle Field. AB - Diagnostic patents usually comprise multiple steps and can be jointly implemented by different parties. However, in the USA, joint implementation may render diagnostic patents unenforceable in light of recent court opinions. Here, I explain how inappropriate claim drafting may render a diagnostic patent vulnerable to joint implementation. PMID- 27262508 TI - Revisiting the 'One Material Fits All' Rule for Cancer Nanotherapy. AB - The promise of (nano)biomaterials for the treatment of cancer can only be realized following a comprehensive scrutiny of the tumor microenvironment. The generic use of 'inert' vehicles that deliver a specific cargo to treat a range of cancer types and disease states obeys the 'one material fits all' rule. However, this approach leads to suboptimal and unpredictable clinical outcomes. The key factors constructing the tumor milieu should guide the design of disease responsive materials. Given the growing availability of nanomaterials for cancer therapy, a material that responds to each patient's needs and, hence, reacts in a graded manner based on disease cues, would pave the way to precision materials for cancer therapy. PMID- 27262509 TI - Patients' perspective on the impact of sentinel node biopsy in oral cancer treatment. AB - OBJECTIVE: Assessment of the impact of a sentinel node biopsy (SNB)-based strategy in cT1/T2 N0 oral cancer on the course of health related quality of life, psychological distress, and shoulder disability, and evaluation of the patients' perspective on neck management strategies. STUDY DESIGN: Fifty-two patients (39 SNB negative; 13 SNB positive) completed the European Organization for Research and Treatment of Cancer (EORTC) questionnaires-QLQ-C30 and QLQ H&N35, and the HADS, IES, and SDQ questionnaires at baseline, after SNB diagnosis and at 6 months of follow-up. Objective shoulder measurements were performed after 2 years and interviews were conducted after 4.5 months of follow-up. RESULTS: All the scores of the questionnaires were not significantly different between SNB negative and SNB positive patients. Objective shoulder functioning was similar. Most patients preferred a SNB-based strategy to an elective neck dissection strategy. CONCLUSIONS: The impact of a SNB-based strategy in patients with cT1/T2 N0 oral cancer is comparable for SNB-negative and SNB-positive patients in terms of health-related quality of life, psychological distress and shoulder functioning. Most patients preferred the SNB-based strategy over the elective neck dissection strategy. PMID- 27262510 TI - ADORA2A genotype modulates interoceptive and exteroceptive processing in a fronto insular network. AB - Facilitated processing of interoceptive and exteroceptive information in the salience network is suggested to promote the development of anxiety and anxiety disorders. Here, it was investigated whether the adenosine 2 A receptor gene (ADORA2A) 1976T/C (rs5751876) variant - previously associated with anxiety disorders and anxiety-related phenotypes as well as general attentional efficiency -was involved in the regulation of this network. In detail, fMRI recordings of 65 healthy participants (female=35) were analyzed regarding ADORA2A genotype effects on brain connectivity related to (1) interoceptive processing in terms of functional connectivity resting-state fMRI, and (2) exteroceptive processing using dynamic causal modeling in task-based fMRI. In a subsample, cardiac interoceptive accuracy was furthermore measured via the Mental Tracking Task. ADORA2A genotype was found to modulate a fronto-insular network at rest (interoceptive processing) and while performing an executive control task (exteroceptive processing). Across both modalities, the ADORA2A TT risk genotype was associated with increased connectivity between the insula and the prefrontal cortex. The strength in connectivity correlated with interoceptive accuracy. It is concluded that alterations in fronto-insular connectivity are modulated by both the adenosinergic system and interoceptive accuracy. Thus, fronto-insular connectivity in synopsis with ADORA2A genotypic information could serve as combined biomarkers for personalized treatment approaches in anxiety disorders targeting exteroceptive and interoceptive dysfunction. PMID- 27262511 TI - Complement factor H interferes with Mycobacterium bovis BCG entry into macrophages and modulates the pro-inflammatory cytokine response. AB - Mycobacterium tuberculosis is an accomplished intracellular pathogen, particularly within the macrophage and this is of the utmost importance in the host-pathogen stand-off observed in the granuloma during latent tuberculosis. Contact with innate immune molecules is one of the primary interactions that can occur with the pathogen M. tuberculosis once inhaled. Complement proteins may play a role in facilitating M. tuberculosis interactions with macrophages. Here, we demonstrate that factor H, a complement regulatory protein that down-regulates complement alternative pathway activation, binds directly to the model organism M. bovis BCG. Binding of factor H reaches saturation at 5-10MUg of factor H/ml, well below the plasma level. C4 binding protein (C4BP) competed with factor H for binding to mycobacteria. Factor H was also found to inhibit uptake of M. bovis BCG by THP-1 macrophage cells in a dose-dependent manner. Real-time qPCR analysis showed stark differential responses of pro- and anti-inflammatory cytokines during the early stages of phagocytosis, as evident from elevated levels of TNF alpha, IL-1beta and IL-6, and a concomitant decrease in IL-10, TGF-beta and IL-12 levels, when THP-1:BCG interaction took place in the presence of factor H. Our results suggest that factor H can interfere with mycobacterial entry into macrophages and modulate inflammatory cytokine responses, particularly during the initial stages of infection, thus affecting the extracellular survival of the pathogen. Our results offer novel insights into complement activation-independent functions of factor H during the host-pathogen interaction in tuberculosis. PMID- 27262512 TI - Testicular expression of SP-A, SP-D and MBL-A is positively regulated by testosterone and modulated by lipopolysaccharide. AB - Pattern recognition proteins viz., Surfactant Protein-A (SP-A), Surfactant Protein-D (SP-D) and Mannan Binding Lectin-A (MBL-A) regulate inflammatory immune responses. In view of their plausible contribution to immune privilege in testis, the present study explored their expression and regulation in murine testis. The testicular expression of SP-A, SP-D and MBL-A significantly increased at puberty and was significantly down-regulated in testosterone suppression model. Of the isolated germ cells, Sertoli cells, myoid cells and Leydig cells, germ cells expressed SP-A, SP-D and MBL-A while myoid cells were found to express MBL-A. SP A and SP-D were localised on head and tail of murine caudal sperm, whereas MBL-A was observed on the connecting piece and tail. Systemic lipopolysaccharide challenge significantly up-regulated SP-A and SP-D levels in murine testis after 24h. Positive regulation of collectins by testosterone and their modulation in response to inflammation implicates their involvement in testicular immune privilege. PMID- 27262513 TI - Immune-inflammatory responses in atherosclerosis: Role of an adaptive immunity mainly driven by T and B cells. AB - Adaptive immune response plays an important role in atherogenesis. In atherosclerosis, the proinflammatory immune response driven by Th1 is predominant but the anti-inflammatory response mediated mainly by regulatory T cells is also present. The role of Th2 and Th17 cells in atherogenesis is still debated. In the plaque, other T helper cells can be observed such as Th9 and Th22 but is little is known about their impact in atherosclerosis. Heterogeneity of CD4(+) T cell subsets presented in the plaque may suggest for plasticity of T cell that can switch the phenotype dependening on the local microenvironment and activating/blocking stimuli. Effector T cells are able to recognize self-antigens released by necrotic and apoptotic vascular cells and induce a humoral immune reaction. Tth cells resided in the germinal centers help B cells to switch the antibody class to the production of high-affinity antibodies. Humoral immunity is mediated by B cells that release antigen-specific antibodies. A variety of B cell subsets were found in human and murine atherosclerotic plaques. In mice, B1 cells could spontaneously produce atheroprotective natural IgM antibodies. Conventional B2 lymphocytes secrete either proatherogenic IgG, IgA, and IgE or atheroprotective IgG and IgM antibodies reactive with oxidation-specific epitopes on atherosclerosis-associated antigens. A small population of innate response activator (IRA) B cells, which is phenotypically intermediate between B1 and B2 cells, produces IgM but possesses proatherosclerotic properties. Finally, there is a minor subset of splenic regulatory B cells (Bregs) that protect against atherosclerotic inflammation through support of generation of Tregs and production of anti-inflammatory cytokines IL-10 and TGF-beta and proapoptotic molecules. PMID- 27262514 TI - Human amniotic epithelial cells attenuate TGF-beta1-induced human dermal fibroblast transformation to myofibroblasts via TGF-beta1/Smad3 pathway. AB - BACKGROUND AIMS: Keloids are raised dermal scars that extend beyond the boundaries of the initial injury. To date, there is no treatment to erase scars completely in humans. Growing evidence has shown that the human amniotic epithelial cells have anti-fibrotic properties and can reduce the fibrosis of lung and liver. However, it is unknown whether and how they can influence human keloids. The aim of this study was to investigate whether factors secreted by human amniotic epithelial cells have anti-fibrotic effects on human keloids and to clarify the potential transduction mechanism. METHODS: Human amniotic epithelial cells were isolated and identified both with flow cytometry and immunofluorescent. The alpha-smooth muscle actin, collagen-I and III gene and protein expression of transforming growth factor (TGF)-beta1-treated human adult dermal fibroblasts were partly abolished by human amniotic epithelial cells conditioned medium through stimulating the expression of matrix metalloproteinase (MMP). Furthermore, human amniotic epithelial cells conditioned medium effectively attenuated nuclear import of the Smad2/3 complex. RESULTS: Soluble human leukocyte antigen G, a human amniotic epithelial cell-derived factor, significantly decreased collagen production in TGF-beta1-induced human dermal fibroblasts, although the effect on collagen production was less than that of human amniotic epithelial cell-conditioned medium. CONCLUSIONS: This study demonstrates that human amniotic epithelial cells conditioned medium could down regulate the expression of fibrosis-related molecules by regulating MMP and tissue inhibitor of metalloproteinase levels, and suppress TGF-beta1-induced fibroblast transition, in which the TGF-beta1/Smad3 pathway is likely involved. These findings suggest that human amniotic epithelial cells are a potential therapeutic compound for the treatment of keloids. PMID- 27262515 TI - Structural analysis of beta-prism lectin from Colocasia esculenta (L.) S chott. AB - The Mannose-binding beta-Prism Colocasia esculenta lectin (beta-PCL) was purified from tubers using ion exchange chromatography. The purified beta-PCL appeared as a single band of ~12kDa on SDS-PAGE. beta-PCL crystallizes in trigonal space group P3121 and diffracted to a resolution of 2.1A. The structure was solved using Molecular replacement using Crocus vernus lectin (PDB: 3MEZ) as a model. From the final refined model to an R-factor of 16.5% and an Rfree of 20.4%, it has been observed that the biological unit consists of two beta-Prism domains augmented through C-terminals swap over to form one of faces for each domain. Calpha superposition of individual domains of beta-PCL with individual domains of other related structures and superposition of whole protein structures were carried out. The higher RMS deviation for the superposition of whole structures suggest that beta-prism domains assume different orientation in each structure. PMID- 27262516 TI - Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors. AB - Chalcone has been reported to be a valid scaffold for the design of monoamine oxidase (MAO) inhibitors. This scenario has amplified the momentum for the discovery of heteroaryl based chalcone MAO inhibitors. In the present study, we have synthesized a series of eleven chlorinated thienyl chalcone derivatives substituted with a different functional groups at the para- position on the ring B and investigated for their ability to inhibit human MAO-A and -B. With the exception of compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4 nitrophenyl)prop-2-en-1-one (TC7), which was a selective MAO-A inhibitor, all the other derivatives inhibited hMAO-B potently and selectively with competitive mode of inhibition. The most potent compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl) 3-(4-ethylphenyl)prop-2-en-1-one (TC6) was found to be the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.31+/-0.02MUM and 16.84, respectively. All the compounds presented in the current study are completely non-toxic with 74-88% viable cells to hepatic cells at 100MUM concentration. Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.2 and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO-B inhibitor TC6. PMID- 27262517 TI - Cutaneous manifestations in antiphospholipid syndrome. PMID- 27262518 TI - Leukocytoclastic vasculitis and infection. Report of a case. AB - Leukocytoclastic vasculitis is the most common cause of cutaneous vasculitis in clinical practice. Its causes are various, among which are certain infections. We report the case of a man (28 years old) who debuted with vasculitic lesions in inferior members compatibles leukocytoclastic vasculitis on pathology. The study of causation is the presence of a positive urethral discharge to Ureaplasma urealyticum, dramatically improving lesions after treatment thereof. PMID- 27262519 TI - Ultrasound and Point Shear Wave Elastography in Livers of Patients with Primary Sclerosing Cholangitis. AB - Point shear wave elastography (pSWE) is an ultrasound-based method for non invasive quantification of liver fibrosis. The objective of this study was to explore liver pSWE in patients with primary sclerosing cholangitis (PSC) for assessment of fibrosis. Fifty-five non-transplant patients with PSC (38 males, 17 females; mean age: 46.4 y) were included and compared with 24 matched controls. Median (range) PSC duration was 8.1 (0-33) y. Ultrasonographic scanning followed by liver stiffness measurement by pSWE was performed using a conventional ultrasound system (Philips iU22). Signs of liver fibrosis on B-mode were identified in 21 patients (38%). Splenomegaly was found in 19 patients (35%) and ascites in two patients (4%). Successful pSWE measurements were achieved in the right liver lobe of all individuals and in the left liver lobe of 36 patients (65.5%). PSC patients had significantly higher median shear wave velocity (SWV) than controls in the right liver (median [range] SWV 1.26 [0.73-2.57] m/s vs. 1.09 [0.88-1.25] m/s, p < 0.001). SWV measured in the left liver lobe and spleen did not differ between PSC patients and controls. Our findings indicate that PSC patients have increased median SWV, indicating more fibrosis compared with controls; however, a wide range of SWV values were obtained among PSC patients, possibly reflecting the various stages in disease development. PMID- 27262520 TI - Feasibility and Usefulness of Intra-Cavitary Contrast-Enhanced Ultrasound in Percutaneous Nephrostomy. AB - The aim of this study was to evaluate the feasibility and utility of intra cavitary contrast enhanced ultrasound (ICCEUS) in guiding percutaneous nephrostomy (PCN) and assessing complications. Forty-five ultrasound-guided PCNs were performed in 35 patients with hydronephrosis resulting from urinary tract obstruction. Ultrasound contrast agent (0.1 mL diluted in 20-30 mL saline) was injected through the puncture needle and the drainage tube to precisely locate the device and obstruction, with the fluoroscopy results considered the gold standard. ICCEUS was performed again the next day to assess complications. All 45 PCNs were successfully performed under the guidance of ultrasound. With ICCEUS, we could confirm the correct insertion of needle and catheter and locate the obstruction in all 35 patients, with fluoroscopic results as the gold standard. Catheter dislodgement was diagnosed by administration of ultrasound contrast agent in 5 patients. Hematoma (1 patient) and urine leakage (1 patient) were also observed. With the advantages of lack of exposure to radiation, performance in real time and bedside availability, ICCEUS has the potential to become a new modality to guide PCN and assess catheter-related complications. PMID- 27262521 TI - Assessment of Diagnostic Accuracy and Efficiency of Categories 4 and 5 of the Second Edition of the BI-RADS Ultrasound Lexicon in Diagnosing Breast Lesions. AB - The purpose of this study was to evaluate the diagnostic accuracy and efficiency of categories 4 and 5 of the second edition of the Breast Imaging Reporting and Data System (BI-RADS) ultrasound (US) lexicon in diagnosing breast lesions. In our retrospective study, 579 lesions in 544 patients were assessed by US as the preliminary diagnosis and classified in subcategories 4a-4c and category 5 based on the second edition of the BI-RADS US lexicon with some obvious changes, such as the redefined margin, new calcification type, associated features and some special cases. Inter-observer agreement was determined. Ultrasound results were compared with the pathologic results for confirmation. Positive predictive values (PPVs) of subcategories 4a-4c were compared with theoretical values using the chi(2) test; the binomial test was used for category 5 lesions. Of the 579 lesions, 212 were confirmed as benign (36.61%), and the remaining 367 lesions were confirmed as borderline/malignant (63.39%). Inter-observer agreement was moderate for subcategories 4a-4c (kappa = 0.52), moderate for subcategories 4a-4c and category 5 (kappa = 0.56) and substantial for categories 4 and 5 (kappa = 0.67). The PPVs for subcategories 4a-4c were 23.74%, 70.67% and 81.25%, respectively. In addition, the total PPV for category 4 was 46.92% (183/390), and the total PPV for category 5 was 97.35% (184/189). Statistical results revealed that the PPVs of subcategories 4a and 4b differed significantly from the theoretical values (p < 0.05); the PPVs of subcategory 4c and category 5 were significantly correlated with the theoretical PPVs (p > 0.05). In conclusion, subcategories 4a and 4b have lower diagnostic efficiency than subcategory 4c and category 5. Inter-observer agreement for subcategories 4a-4c remains to be improved. The most common features of subcategories 4a-4c differ, but overlap. It is recommended that inexperienced doctors in primary hospitals not classify lesions into subcategories in clinical practice. PMID- 27262522 TI - Pinworm diversity in free-ranging howler monkeys (Alouatta spp.) in Mexico: Morphological and molecular evidence for two new Trypanoxyuris species (Nematoda: Oxyuridae). AB - Two new species of Trypanoxyuris are described from the intestine of free-ranging howler monkeys in Mexico, Trypanoxyuris multilabiatus n. sp. from the mantled howler Alouatta palliata, and Trypanoxyuris pigrae n. sp. from the black howler Alouatta pigra. An integrative taxonomic approach is followed, where conspicuous morphological traits and phylogenetic trees based on DNA sequences are used to test the validity of the two new species. The mitochondrial cytochrome oxidase subunit 1 gene, and the nuclear ribosomal 18S and 28S rRNA genes were used for evolutionary analyses, with the concatenated dataset of all three genes used for maximum likelihood and Bayesian phylogenetic analyses. The two new species of pinworms from howler monkeys were morphologically distinct and formed reciprocally monophyletic lineages in molecular phylogenetic trees. The three species from howler monkeys, T. multilabiatus n. sp., T. pigrae n. sp., and Trypanoxyuris minutus, formed a monophyletic group with high bootstrap and posterior probability support values. Phylogenetic patterns inferred from sequence data support the hypothesis of a close evolutionary association between these primate hosts and their pinworm parasites. The results suggest that the diversity of pinworm parasites from Neotropical primates might be underestimated. PMID- 27262524 TI - How do young children expect others to address resource inequalities between groups? AB - Age-related changes in young children's expectations for others' resource allocation decisions were investigated. Children ages 3 to 6years (N=80) were introduced to an inequality of resources between two groups. Participants gave their expectations for (a) how a member of the group with more resources (advantaged group) and a member of the group with fewer resources (disadvantaged group) would evaluate the inequality (okay or not okay), (b) which group each of the two individuals would prefer (ingroup or outgroup), and (c) how each of the two individuals would allocate subsequent resources between the groups. Findings revealed children's differing expectations for how others would address resource inequalities based on group status. Children expected that if the disadvantaged group member evaluated the inequality negatively then he or she would reduce the disparity. But children expected that if the advantaged group member evaluated the inequality positively then he or she would increase the disparity. Furthermore, 5- and 6-year-olds, but not 3- and 4-year-olds, expected individuals to seek more for their ingroup if they preferred their ingroup over the outgroup. Different from previous research on children's own resource allocation decisions, these findings reveal the circumstances under which children expect others to perpetuate or attenuate resource inequalities between groups. PMID- 27262523 TI - Programmed cell death 4 in bacterially-challenged Apostichopus japonicus: Molecular cloning, expression analysis and functional characterization. AB - Programmed cell death 4 (PDCD4) plays a crucial role in modulating cellular signals, mainly via TOLL cascades during the immune response. In the present study, a novel PDCD4 homologue gene (denoted as AjPDCD4) was cloned from the sea cucumber Apostichopus japonicus using RACE. The full-length AjPDCD4 cDNA comprised a 366bp 5'-UTR, a 418bp 3'-UTR, and a 1353bp open reading frame encoding a 450 amino acid residue protein with two typical MA3 domains. Phylogenetic analysis revealed that AjPDCD4 belonged to the invertebrate PDCD4 family. Spatial expression analysis indicated that AjPDCD4 mRNA transcripts are expressed at a high level in the tentacles and at a low level in muscle compared with coelomocytes. Vibrio splendidus challenge and LPS exposure could both significantly down-regulate AjPDCD4 mRNA expression. More importantly, we found that ultraviolet (UV)-induced ROS production and DNA damage were greatly repressed in AjPDCD4-knockdown coelomocytes. Meanwhile, the expression levels of the NF-kappa B homologue, p105, were synchronously up-regulated in the same conditions. All of these results indicated that AjPDCD4 is involved in modulating DNA damage and ROS production in sea cucumber, perhaps by affecting the TLR pathway. PMID- 27262525 TI - Building on the Shoulders of Giants: A Model for Developing Medical Education Scholarship Using I-PASS. PMID- 27262526 TI - Old dogs and new tricks in antimicrobial discovery. AB - The discovery of new antibiotics is crucial if we are to avoid a future in which simple infections once again lead to death. New antibiotics were traditionally discovered by analyzing extracts from cultured soil-derived microbes. However, in the last few years only a few new antibiotic classes have been identified using this method. Attempts to apply target-based screening approaches to antibiotic discovery have also proven to be unproductive. In this article, we describe how DNA sequencing and bioinformatic techniques are revolutionizing natural product discovery leading to new natural product antibiotics sourced from both cultivated and uncultivated microbes. New chemical structures are also being 'crowd sourced' from chemists around the world, and 'forgotten' antibiotics repositioned for clinical trials after chemical or biochemical modification of the original natural product. Collectively such approaches have the potential to revamp antibiotic lead discovery and re-invigorate the antibiotic pipeline. PMID- 27262527 TI - BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized alpha helix of BCL2) not always convinces BAX (BCL-2-associated X protein) for apoptosis. AB - The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized alpha helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The alpha1-alpha2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/alpha2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge. PMID- 27262528 TI - Towards cheminformatics-based estimation of drug therapeutic index: Predicting the protective index of anticonvulsants using a new quantitative structure-index relationship approach. AB - The overall efficacy and safety profile of a new drug is partially evaluated by the therapeutic index in clinical studies and by the protective index (PI) in preclinical studies. In-silico predictive methods may facilitate the assessment of these indicators. Although QSAR and QSTR models can be used for predicting PI, their predictive capability has not been evaluated. To test this capability, we developed QSAR and QSTR models for predicting the activity and toxicity of anticonvulsants at accuracy levels above the literature-reported threshold (LT) of good QSAR models as tested by both the internal 5-fold cross validation and external validation method. These models showed significantly compromised PI predictive capability due to the cumulative errors of the QSAR and QSTR models. Therefore, in this investigation a new quantitative structure-index relationship (QSIR) model was devised and it showed improved PI predictive capability that superseded the LT of good QSAR models. The QSAR, QSTR and QSIR models were developed using support vector regression (SVR) method with the parameters optimized by using the greedy search method. The molecular descriptors relevant to the prediction of anticonvulsant activities, toxicities and PIs were analyzed by a recursive feature elimination method. The selected molecular descriptors are primarily associated with the drug-like, pharmacological and toxicological features and those used in the published anticonvulsant QSAR and QSTR models. This study suggested that QSIR is useful for estimating the therapeutic index of drug candidates. PMID- 27262529 TI - Second-order nonlinear optical responses of carboranyl-substituted indole/indoline derivatives: impact of different substituents. AB - Carborane has been the subject of great interest over the last decades due to its high structural, chemical, biological stability and diverse applications. In the present work, carboranyl-substituted indole/indoline compounds and their functionalized derivatives have been systematically investigated by density functional theory (DFT) method with the view of assessing their electronic structures and first hyperpolarizabilities. Significantly, the first hyperpolarizabilities can be obviously enhanced by the introduction of a strong electron-withdrawing group for closed-ring forms, while the strong electron donating group is beneficial for large first hyperpolarizabilities for open-ring forms. It indicates that the NLO properties of these compounds can be enhanced by controlling their relative substituent groups. Furthermore, the time-dependent DFT calculation illustrates that the enhancement of the first hyperpolarizabilities are found due to the obvious charge transfer (CT) transition, and closed-ring forms have a significant difference on the CT patterns versus open-ring ones. Investigation of the structure-property relationship and substituent effects at the molecular level can benefit for further exploration of carboranyl-substituted indole/indoline derivatives with versatile and fascinating NLO properties. PMID- 27262530 TI - Survival advantage with para aortic lymphadenectomy in peri-ampullary cancer: A retrospective cohort study. AB - BACKGROUND: Metastatic para aortic lymph nodes (PALN) in patients with peri ampullary cancer entail poor prognosis. Role of curative surgery in these patients remains debatable. The objective of the current study was to evaluate outcome after extended pancreaticoduodenectomy (PD) in patients with and without positive PALN. METHODS: We reviewed 65 patients who underwent extended PD with PALN removal between 2011 and 2014. Patients were divided into two groups; those with positive PALN and those without. Patients were sub classified for pancreatic and non-pancreatic cancer. Outcome was determined based on median and estimated 3 year overall survival. RESULTS: Median age was 57 (32-85) years. PALN were involved in 15 (23%) patients. Overall 3 year survival for patients with and without positive PALN was 60% and 54% (P = 0.7). Significant difference in survival was present between patients with pancreatic cancer and positive PALN [9 (3-12) months] versus non-pancreatic cancers with positive PALN [17.5 (13-38) months] (P = 0.02). Four out of five patients with pancreatic cancer and positive PALN had survival >6 months and 3 out of these 5 patients were alive at the last follow up. CONCLUSION: Curative surgery may benefit some patients with pancreatic cancer and positive PALN and should be considered selectively. PMID- 27262531 TI - Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain. AB - Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro inflammatory MHCII+ spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPalpha)+ microglia/macrophages were found in the PFC of SNI rats. Interestingly in naive rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII+/CD172a+ ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII+ microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at the chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain. PMID- 27262532 TI - End-processing nucleases and phosphodiesterases: An elite supporting cast for the non-homologous end joining pathway of DNA double-strand break repair. AB - Nonhomologous end joining (NHEJ) is an error-prone DNA double-strand break repair pathway that is active throughout the cell cycle. A substantial fraction of NHEJ repair events show deletions and, less often, insertions in the repair joints, suggesting an end-processing step comprising the removal of mismatched or damaged nucleotides by nucleases and other phosphodiesterases, as well as subsequent strand extension by polymerases. A wide range of nucleases, including Artemis, Metnase, APLF, Mre11, CtIP, APE1, APE2 and WRN, are biochemically competent to carry out such double-strand break end processing, and have been implicated in NHEJ by at least circumstantial evidence. Several additional DNA end-specific phosphodiesterases, including TDP1, TDP2 and aprataxin are available to resolve various non-nucleotide moieties at DSB ends. This review summarizes the biochemical specificities of these enzymes and the evidence for their participation in the NHEJ pathway. PMID- 27262533 TI - Management of large incisional hernias with loss of domain: A prospective series of patients prepared by progressive preoperative pneumoperitoneum. AB - BACKGROUND: The surgical treatment of giant incisional hernias with loss of domain is challenging due to the possibility of intra-abdominal hypertension after the herniated content is returned to the peritoneal cavity. Progressive preoperative pneumoperitoneum has been described before repair of the hernia, although its efficacy has not been demonstrated clearly. Our aim was to evaluate the efficacy of preoperative progressive pneumoperitoneum in expanding the volume of the peritoneal cavity and the outcomes after surgical treatment of incisional hernias with loss of domain. METHODS: All consecutive patients with incisional hernias with loss of domain undergoing preoperative progressive pneumoperitoneum and operative repair were included in a prospective observational study. All patients had pre- and postoperative progressive pneumoperitoneum computed tomography of the abdomen. Open incisional hernias with loss of domain repair consisted of anatomic reconstruction of the abdominal wall by complete closure of the defect and reinforcement with a sublay synthetic mesh, whenever possible. RESULTS: The cohort was composed of 45 patients (mean age, 60.5 years). Before the preoperative progressive pneumoperitoneum, the mean volume of the herniated content was 38% of the total peritoneal volume. The mean abdominal volume increased by 53% after the preoperative progressive pneumoperitoneum. One patient died during preoperative progressive pneumoperitoneum, but the postoperative mortality was zero, giving a mortality rate of 2% to the treatment using preoperative progressive pneumoperitoneum. Complete reduction of the herniated content intraperitoneally with primary closure of the fascia was achieved in 42 out of 45 patients (94%). Reinforcement by a synthetic mesh was possible in 37 patients (84%). Overall, surgical complications related directly to the operative procedure occured in 48% of cases. The rates of overall and severe morbidity were 75 and 34%, respectively. At a mean follow-up of 18.6 months, the recurrence rate was 8% (3 out of 37 patients) with non-absorbable meshes and 57% (4 out of 7 patients) with absorbable mesh. CONCLUSION: Preoperative progressive pneumoperitoneum increased the volume of the abdominal cavity in patients with incisional hernias with loss of domain, allowing complete reduction of the herniated content and primary fascial closure in 94% of patients, with acceptable overall morbidity. PMID- 27262534 TI - Student perceptions of a simulation-based flipped classroom for the surgery clerkship: A mixed-methods study. AB - BACKGROUND: The flipped classroom, a blended learning paradigm that uses pre session online videos reinforced with interactive sessions, has been proposed as an alternative to traditional lectures. This article investigates medical students' perceptions of a simulation-based, flipped classroom for the surgery clerkship and suggests best practices for implementation in this setting. METHODS: A prospective cohort of students (n = 89), who were enrolled in the surgery clerkship during a 1-year period, was taught via a simulation-based, flipped classroom approach. Students completed an anonymous, end-of-clerkship survey regarding their perceptions of the curriculum. Quantitative analysis of Likert responses and qualitative analysis of narrative responses were performed. RESULTS: Students' perceptions of the curriculum were positive, with 90% rating it excellent or outstanding. The majority reported the curriculum should be continued (95%) and applied to other clerkships (84%). The component received most favorably by the students was the simulation-based skill sessions. Students rated the effectiveness of the Khan Academy-style videos the highest compared with other video formats (P < .001). Qualitative analysis identified 21 subthemes in 4 domains: general positive feedback, educational content, learning environment, and specific benefits to medical students. The students reported that the learning environment fostered accountability and self-directed learning. Specific perceived benefits included preparation for the clinical rotation and the National Board of Medical Examiners shelf exam, decreased class time, socialization with peers, and faculty interaction. CONCLUSION: Medical students' perceptions of a simulation-based, flipped classroom in the surgery clerkship were overwhelmingly positive. The flipped classroom approach can be applied successfully in a surgery clerkship setting and may offer additional benefits compared with traditional lecture-based curricula. PMID- 27262535 TI - Ethanol extract of Cyclolepis genistoides D. Don (palo azul) induces formation of myotubes, which involves differentiation of C2C12 myoblast cells. AB - In this study, we examined the cell differentiation effect of an ethanol extract of Cyclolepis genistoides D. Don, a herbaceous perennial belonging to the family Asteraceae (vernacular name: palo azul). Palo azul has numerous physiological effects that contribute to the prevention of metabolic syndromes, although the mechanism remains unclear. We previously suggested that palo azul has antidiabetic activity via an adipose differentiation effect. Here, we focused on whether palo azul promoted the differentiation of myoblasts. The mouse muscle myoblast cell line C2C12 was cultured and differentiated using horse serum with or without an ethanol extract of palo azul (12.5-200 MUg/mL). Quantitative real time polymerase chain reaction was performed to evaluate differentiation markers, including insulin-like growth factor-1 and myogenin. To evaluate myotube formation, myosin heavy-chain (MHC) expression and localization were detected by immunohistochemistry. Palo azul increased the expression of the differentiation markers. Furthermore, immunohistochemistry analysis revealed increased formation of MHC myotubes after palo azul treatment along with increased diameter and fusion indices of the myotubes. The expression level of MHC was also increased. In conclusion, palo azul may increase muscle mass in the body and improve insulin resistance conditions by facilitating the formation of myotubes by promoting myocyte differentiation. PMID- 27262538 TI - Assessment of lutein and zeaxanthin status and dietary markers as predictors of the contrast threshold in 2 age groups of men and women. AB - Lutein and zeaxanthin (L + Z) status is associated with the macular pigment (MP). The relationship between MP and visual function is controversial. We hypothesized that, within the framework of nutrition, visual function was related to MP and nutritional and/or/dietary factors influencing it. A cross-sectional study was performed in 108 volunteers divided into 2 age groups (20-35 years; 45-65 years), each 27 women and 27 men, to assess the relationship between MP optical density (MPOD) and contrast threshold (CT), considering the influence of L + Z and, fruit and vegetable (F + V) intake. MPOD, L + Z in serum and dietary intake were determined using heterochromatic flicker photometry, high-performance liquid chromatography and 3-day food records, respectively. CT was measured with the CGT 1000 Contrast Glaretester at 6 stimulus sizes, with and without glare. Spearman correlation coefficient and a generalized linear model were used for the statistical study. MPOD and CT were higher and lower, respectively in younger than in elder individuals (P < .000) and were correlated only in the older group. CT were higher under glare conditions, at the intermediate and smaller visual angles, with greater differences in the older (P < .003) than the younger group (P < .014). In the total sample, CT correlated inversely with MPOD (correlation coefficients and P values ranging from -.245 to -.152 and from .000 to .026, respectively) and directly with F + V intake (correlation coefficients and P values ranging from -.265 to -.176 and from .000 to .010, respectively). As predictors of CT in the total sample, MPOD, F + V (every 100 g/d) and sex were identified (beta coefficients ranged from -0.01 to -1.86; from 0.01 to 0.08 and from 0.01 to 0.40, respectively). CT revealed age-specific nutritional predictors: MPOD and serum lutein in the 45- to 65-year group, and F + V intake in the 20- to 35-year group. PMID- 27262537 TI - Mulberry ethanol extract attenuates hepatic steatosis and insulin resistance in high-fat diet-fed mice. AB - Nonalcoholic fatty liver disease is one of the most common complications of obesity. Mulberry is an important source of phytochemicals, such as anthocyanins, polyphenols and flavonoids, which are related to its antioxidant activity. In this study, we developed a hypothesis that mulberry exerted beneficial effects on metabolic disorders and evaluated the influence of the mulberry ethanol extract (MEE) on high-fat diet-induced hepatic steatosis and insulin resistance in mice. Thirty-six male C57BL/6J mice were assigned into 3 groups and fed either a low fat diet or a high-fat diet with or without supplementation with MEE. Our results showed that administration of MEE reduced diet-induced body weight gain, improved high-fat diet-induced hepatic steatosis and adipose hypertrophy, alleviated insulin resistance, and improved glucose homeostasis. Analysis of hepatic gene expression indicated that MEE treatment changed the expression profile of genes involved in lipid and cholesterol metabolism. In conclusion, the present study demonstrated that MEE supplementation protected mice from high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Moreover, the protective effects of MEE were associated with the induction of fatty acid oxidation and decreased fatty acid and cholesterol biosynthesis. PMID- 27262536 TI - High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice. AB - Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P<.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P<.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P<.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects. PMID- 27262540 TI - Early switch in tyrosine kinase inhibitor therapy for patients with chronic myeloid leukemia: An emerging clinical question. AB - Response to frontline BCR-ABL1-targeted tyrosine kinase inhibitor (TKI) therapy is associated with an improved prognosis for patients with chronic myeloid leukemia (CML). Accordingly, the National Comprehensive Cancer Network (NCCN) and European LeukemiaNet (ELN) recommend the use of specific response milestones (eg, BCR-ABL1<=10% on the International Scale at 3 months) to assess treatment success and inform follow-up care, including potentially switching to another TKI therapy. However, prior to any treatment change, the potential benefits and risks of each TKI and the goals of the patient must be considered. Here we review current NCCN and ELN response recommendations for patients with CML, highlight the impact of early responses on long-term prognosis, and discuss several reasons patients may consider a switch in TKI therapy. We also review completed and ongoing clinical studies involving a switch in frontline therapy for patients with CML, including those with a treatment-free remission phase. PMID- 27262539 TI - Monitoring drug induced apoptosis and treatment sensitivity in non-small cell lung carcinoma using dielectrophoresis. AB - Non-invasive real time methods for characterizing biomolecular events that contribute towards apoptotic kinetics would be of significant importance in the field of cancer biology. Effective drug-induced apoptosis is an important factor for establishing the relationship between cancer genetics and treatment sensitivity. The objective of this study was to develop a non-invasive technique to characterize cancer cells that are undergoing drug-induced apoptosis. We used dielectrophoresis to determine apoptotic cells as early as 2h post drug treatment as compared to 24h with standard flow cytometry method using non-small cell lung cancer (NSCLC) adenocarcinoma cell line (HCC1833) as a study model. Our studies have shown significant differences in apoptotic cells by chromatin condensation, formation of apoptotic bodies and exposure of phosphatidylserine (PS) on the extracellular surface when the cells where treated with a potent Bcl-2 family inhibitor drug (ABT-263). Time lapse dielectrophoretic studies were performed over 24h period after exposure to ABT-263 at clinically relevant concentrations. The dielectrophoretic studies were compared to Annexin-V FITC flow assay for the detection of PS in mid-stage apoptosis using flow cytometry. As a result of physical and biochemical changes, inherent dielectric properties of cells undergoing varying stages of apoptosis showed amplified changes in their cytoplasmic and membrane capacitance. In addition, zeta potential of these fixed isolated cells was measured to obtain direct correlation to biomolecular events. PMID- 27262541 TI - Regenerated cellulose capsules for controlled drug delivery: Part III. Developing a fabrication method and evaluating extemporaneous utility for controlled release. AB - In this article, we describe a method to utilize cellulose dissolved in dimethyl sulfoxide and paraformaldehyde solvent system to fabricate two-piece regenerated cellulose hard shell capsules for their potential use as an oral controlled drug delivery a priori vehicle. A systematic evaluation of solution rheology as well as resulting capsule mechanical, visual and thermal analysis was performed to develop a suitable method to repeatedly fabricate RC hard shell capsule halves. Because of the viscoelastic nature of the cellulose solution, a combination of dip-coating and casting method, herein referred to as dip-casting method, was developed. The dip-casting method was formalized by utilizing two-stage 2(2) full factorial design approach in order to determine a suitable approach to fabricate capsules with minimal variability. Thermal annealing is responsible for imparting shape rigidity of the capsules. Proof-of-concept analysis for the utility of these capsules in controlled drug delivery was performed by evaluating the release of KCl from them as well as from commercially available USP equivalent formulations. Release of KCl from cellulose capsules was comparable to extended release capsule formulation. PMID- 27262543 TI - Unusual Case of Multiple Lateral Spinal Dermal Sinuses in a Child. PMID- 27262542 TI - A novel hybrid drug between two potent anti-tubulin agents as a potential prolonged anticancer approach. AB - We report the design, synthesis and biological characterisation of a novel hybrid drug by conjugation of two tubulin inhibitors, a hemiasterlin derivative A (H-Mpa Tle-Aha-OH), obtained by condensation of three non-natural amino acids, and cis 3,4',5-trimethoxy-3'aminostilbene (B). As we have previously demonstrated synergy between A and B, we used a monocarbonyl derivative of triethylene glycol as linker (L) to synthesise compounds A-L and A-L-B; via HPLC we analysed the release of its potential hydrolysis products A, A-L, B and B-L in physiological fluids: the hybrid A-L-B undergo hydrolysis in rat whole blood of the ester bond between A and L (half-life=118.2+/-9.5min) but not the carbamate bond between B and L; the hydrolysis product B-L was further hydrolyzed, but with a slower rate (half-life=288+/-12min). The compound A-L was the faster hydrolyzed conjugate (half-life=25.4+/-1.1min). The inhibitory activity of the compounds against SKOV3 ovarian cancer cell growth was analysed. The IC50 values were 7.48+/-1.27nM for A, 40.3+/-6.28nM for B, 738+/-38.5nM for A-L and 37.9+/-2.11nM for A-L-B. The anticancer effect of A-L-B was evidenced to be obtained via microtubule dynamics suppression. Finally, we stated the expression of the active efflux transporters P-gp (ABCB1) and MRP1 (ABCC1) in the human normal colon epithelial NCM460 cell line by reverse-transcription PCR. Via permeation studies across NCM460 monolayers we demonstrate the poor aptitude of A to interact with active efflux transporters (AET): indeed, the ratio between its permeability coefficients for the basolateral (B)->apical (A) and B->A transport was 1.5+/-0.1, near to the ratio of taltobulin (1.12+/-0.06), an hemiasterlin derivative able to elude AETs, and significantly different form the ratio of celiprolol (3.4+/-0.2), an AET substrate. PMID- 27262544 TI - Acid Gastroesophageal Reflux Disease and Apparent Life-Threatening Events: Simultaneous pH-metry and Cardiorespiratory Monitoring. AB - AIM: To investigate the prevalence and the characteristics of gastroesophageal reflux disease (GERD) in infants with apparent life threatening events (ALTE). MATERIALS AND METHODS: Infants with at least one episode of ALTE in absence of predisposing factors were included. All infants underwent a cardiorespiratory recording with simultaneous 24-hour pH-monitoring. Patients were divided into 3 groups according to the severity of GERD: A. Reflux Index (RI) <3%, B. RI = 3-7%, C. RI >7%. Monthly evaluations were performed and the anti-reflux therapy was maintained till normalization of monitoring and clinic. RESULTS: 41 infants were enrolled. GERD was found in 80% of patients (moderate in 54%, severe in 27%). A normalization of the cardiorespiratory tracks was recorded on average after 1 month for group A, 7 months for the group B and 9.5 months for group C. A significant difference was registered between group A and both group B and C (P < 0.0001), as well as between the group B and C (P < 0.05). CONCLUSION: GERD influences significantly the time of normalization of the cardiorespiratory monitoring in infants with ALTE. GERD diagnosis and treatment are mandatory in these patients. PMID- 27262545 TI - Re-Epithelialization of Pathological Cutaneous Wounds Is Improved by Local Mineralocorticoid Receptor Antagonism. AB - Impaired cutaneous wound healing is a social burden. It occurs as a consequence of glucocorticoid treatment in several pathologies. Glucocorticoids (GC) bind not only to the glucocorticoid receptor but also to the mineralocorticoid receptor (MR), both expressed by keratinocytes. In addition to its beneficial effects through the glucocorticoid receptor, GC exposure may lead to inappropriate MR occupancy. We hypothesized that dermatological use of MR antagonists (MRA) might be beneficial by overcoming the negative impact of GC treatment on pathological wounds. The potent GC clobetasol, applied as an ointment to mouse skin, or added to cultured human skin explants, induced delayed wound closure and outgrowth of epidermis with reduced proliferation of keratinocytes. Delayed wound re epithelialization was rescued by local MRA application. Normal skin was unaffected by MRA. The benefit of MR blockade is explained by the increased expression of MR in clobetasol-treated mouse skin. Blockade of the epithelial sodium channel by phenamil also rescued cultured human skin explants from GC impaired growth of the epidermis. MRA application over post-biopsy wounds of clobetasol-treated skin zones of healthy volunteers (from the Interest of Topical Spironolactone's Administration to Prevent Corticoid-induced Epidermal Atrophy clinical trial) also accelerated wound closure. In conclusion, we propose repositioning MRA for cutaneous application to improve delayed wound closure occurring in pathology. PMID- 27262546 TI - Evolution of synovitis in osteoarthritic knees and its association with clinical features. AB - OBJECTIVE: To investigate the course of synovitis on contrast-enhanced magnetic resonance images (CE-MRI) in osteoarthritic knees over 2 years, and its association with pain and cartilage deterioration. DESIGN: Consecutive patients (n = 39, mean age 61 years, 79% woman, median (range) body mass index (BMI) 29 (24-48) kg/mm2) with clinical osteoarthritis (OA) were included. Baseline and follow-up CE-MRI (3 T) were scored paired in chronological order for synovitis (semi-quantitatively at 11 sites (range 0-22)), cartilage deterioration and bone marrow lesions (BMLs) (semi-quantitatively according to Knee Osteoarthritis Scoring System (KOSS)). Changes in sum scores were calculated. Cartilage deterioration was defined as change of >=2 above the smallest detectable change (SDC). Pain was assessed by standardized questionnaires. Analysis of covariance (ANCOVA) and linear regression models were used to investigate association between synovitis change and cartilage deterioration and between synovitis change or cartilage deterioration and change in pain. RESULTS: The total synovitis score did not change over 2 years (mean change 0.2 (standard deviation (SD) 3.2)), although changes in individual patients were observed. Cartilage deterioration was observed in 51% of patients. Synovitis change score was lower in patients without compared to patients with cartilage deterioration, taking BML change in account (mean difference -2.1 (-4.1 to -0.1)). Change in synovitis was not associated with change in pain, whereas cartilage deterioration was associated with change in Intermittent and Constant OsteoArthritis Pain (ICOAP) constant pain in adjusted models (unstandardised coefficient (B) (95% confidence interval (CI)) 2.8 (0.4-5.3)). CONCLUSIONS: In individual patients synovitis fluctuates during disease course. Synovitis change was not associated with change in pain. Increase in synovitis is associated with cartilage deterioration, suggesting a role for synovitis as a target for disease-modifying treatment. PMID- 27262547 TI - Reductive transformation of hexabromocyclododecane (HBCD) by FeS. AB - Both iron monosulfide (FeS) and brominated flame retardants (BFRs) are widely found at relatively high levels in anoxic sediments, but little is known about the reactions of FeS with BFRs. Prior studies showed that FeS was variously reactive with chlorinated organic pollutants in many anoxic environments. It is intuitive that FeS is also reactive with BFRs under anoxic conditions. This study was initiated to test such a hypothesis by quantifying the rates of reductive transformation of tetrabromobisphenol A (TBBPA), decabrominated diphenyl ether (decaBDE) and hexabromocyclododecane (HBCD) using synthetic FeS as the reactive agent. The results showed that over 90% of HBCD was transformed by FeS within 24 h, whereas both TBBPA and decaBDE were found nonreactive within 2 days. The transformation of HBCD followed a pseudo-first-order rate kinetic and the observed rate constants were dependent on the initial concentrations of FeS and HBCD. The transformation rates of beta- and gamma-HBCD were significantly faster than that of alpha-HBCD. Analysis of bromine ion and other transformation products suggested that sequential dibromoelimination to form 1,5,9 cyclododecatriene was likely to be a dominant pathway for the reductive transformation of HBCD by FeS. Surface characterization of FeS by XPS indicated that both Fe(II) and S(-II) on the FeS surface might have contributed considerably to the transformation of HBCD. These findings imply that FeS may play an important role in natural attenuation of HBCD and that it may be used as a reactive agent for treating HBCD-contaminated sediments. PMID- 27262548 TI - Contribution of assimilable organic carbon to biological fouling in seawater reverse osmosis membrane treatment. AB - Biological fouling occurs on RO membranes when bacteria and nutrients are present in conditions that are conducive to growth and proliferation of the bacteria. Controlling microbial growth on the membranes is typically limited to biocide application (i.e., disinfectants) in seawater RO plants. However, biological growth and subsequent fouling has not been well-managed. Pretreatment has not been focused on nutrient limitation. This project used a biological assay, the assimilable organic carbon (AOC) test to evaluate pretreatment effects on the nutrient supply. The AOC test provided a useful surrogate measurement for the biodegradability or biofouling potential of RO feed water. Biofouling observed in controlled conditions at the bench- and pilot-scale resulted in statistically significant correlations between AOC and the operational effects caused by biofouling. Membrane fouling rates are observed through operational changes over time such as increased differential pressure between the membrane feed and concentrate locations and decreased permeate flux through the membrane. In full scale plants there were strong correlations when AOC was used as a predictor variable for increased differential pressure (0.28-0.55 bar from September December 2012) and decreased specific flux (1.40 L per hour/(m(2) . bar)). Increased differential pressure was associated with RO membrane biological fouling when the median AOC was 50 MUg/L during pilot testing. Conditions were also evaluated at the bench-scale using a flat sheet RO membrane. In a comparison test using 30 and 1000 MUg/L AOC, fouling was detected on more portions of the membrane when AOC was higher. Biofilm and bacterial deposits were apparent from scanning electron microscope imaging and biomass measurements using ATP. PMID- 27262550 TI - Propidium monoazide RTqPCR assays for the assessment of hepatitis A inactivation and for a better estimation of the health risk of contaminated waters. AB - The waterborne transmission of hepatitis A virus (HAV), the main cause of acute hepatitis, is well documented. Recently, two ISO proposals for sensitive determination of this pathogen by RTqPCR in water and food have been published (ISO/TS 15216-1 and ISO/TS 15216-2), and could enable the formulation of regulatory standards for viruses in the near future. However, since detected viral genomes do not always correlate with virus infectivity, molecular approaches need to be optimized to better predict infectivity of contaminated samples. Two methods involving the use of propidium monoazide (PMA), with or without Triton X-100, prior to RTqPCR amplification were optimized and adapted to infer the performance of infectious viral inactivation upon two different water treatments: free chlorine and high temperature. Significant correlations between the decrease of genome copies and infectivity were found for both inactivation procedures. The best procedure to infer chlorine inactivation was the PMA-RTqPCR assay, in which 1, 2 or 3-log genome copies reductions corresponded to reductions of infectious viruses of 2.61 +/- 0.55, 3.76 +/- 0.53 and 4.92 +/- 0.76 logs, respectively. For heat-inactivated viruses, the best method was the PMA/Triton RTqPCR assay, with a 1, 2 or 3-log genome reduction corresponding to reductions of infectious viruses of 2.15 +/- 1.31, 2.99 +/- 0.79 and 3.83 +/- 0.70 logs, respectively. Finally, the level of damaged virions was evaluated in distinct types of water naturally contaminated with HAV. While most HAV genomes quantified in sewage corresponded to undamaged capsids, the analysis of a river water sample indicated that more than 98% of viruses were not infectious. Although the PMA/Triton-RTqPCR assay may still overestimate infectivity, it is more reliable than the RTqPCR alone and it seems to be a rapid and cost-effective method that can be applied on different types of water, and that it undeniably provides a more accurate measure of the health risk associated to contaminated waters. PMID- 27262549 TI - Comparison of microbial communities of activated sludge and membrane biofilm in 10 full-scale membrane bioreactors. AB - Operation of membrane bioreactors (MBRs) for wastewater treatment is hampered by the membrane biofouling resulting from microbial activities. However, the knowledge of the microbial ecology of both biofilm and activated sludge in MBRs has not been sufficient. In this study, we scrutinized microbial communities of biofilm and activated sludge from 10 full-scale MBR plants. Overall, Flavobacterium, Dechloromonas and Nitrospira were abundant in order of abundance in biofilm, whereas Dechloromonas, Flavobacterium and Haliscomenobacter in activated sludge. Community structure was analyzed in either biofilm or activated sludge. Among MBRs, as expected, not only diversity of microbial community but also its composition was different from one another (p < 0.05). Between the biofilm and activated sludge, community composition made significant difference, but its diversity measures (i.e., alpha diversity, e.g., richness, diversity and evenness) did not (p > 0.05). Effects of ten environmental factors on community change were investigated using Spearman correlation. MLSS, HRT, F/M ratio and SADm explained the variation of microbial composition in the biofilm, whereas only MLSS did in the activated sludge. Microbial networks were constructed with the 10 environmental factors. The network results revealed that there were different topological characteristics between the biofilm and activated sludge networks, in which each of the 4 factors had different associations with microbial nodes. These results indicated that the different microbial associations were responsible for the variation of community composition between the biofilm and activated sludge. PMID- 27262551 TI - Fate and implication of acetylacetone in photochemical processes for water treatment. AB - Acetylacetone (AA), due to the peculiar enol-keto structures, has attracted wide scientific interests. In terms of photo-decolorization, it works much more efficiently than the well-known H2O2. However, there is very limited information on the photochemistry of AA in aqueous solutions. Herein, the photolysis kinetics, quantum yield, mass balance, decomposition pathway, and bioavailability of AA during UV irradiation were systematically investigated. It seems that photophysical processes predominated over photochemical ones when AA was irradiated with UV light. Although the quantum yield of AA (0.116) was much lower than that of H2O2 (1.0), the stronger light absorption of AA and the better overlap of the AA absorption spectrum with the solar emission spectrum, as well as the direct energy/electron transfer mechanisms, ensured its high efficiency in photochemical processes. The main degradation products of AA in photochemical processes were similar to the metabolic products in bio-fermentation. Besides, the irradiated AA solution showed a high bioavailability to the cells in activated sludge. Therefore, the UV/AA process might be a promising pre-treatment approach for bio-treatment. The results provide new insights into the photochemical fate and implication of beta-diketones in aqueous solutions. PMID- 27262552 TI - Evaluating Contaminants of Emerging Concern as tracers of wastewater from septic systems. AB - Bacterial and nutrient contamination from anthropogenic sources impacts fresh and marine waters, reducing water quality and restricting recreational and commercial activities. In many cases the source of this contamination is ambiguous, and a tracer or set of tracers linking contamination to source would be valuable. In this work, the effectiveness of utilizing a suite of Contaminants of Emerging Concern (CECs) as tracers of bacteria from human septic system effluent is investigated. Field sampling was performed at more than 20 locations over approximately 18 months and analyzed for a suite of CECs and fecal coliform bacteria. The sampling locations included seeps and small freshwater discharges to the shoreline. Sites were selected and grouped according to level of impact by septic systems as determined by previous field sampling programs. A subset of selected locations had been positively identified as being impacted by effluent from failing septic systems through dye testing. The CECs were selected based on their predominant use, their frequency of use, and putative fate and transport properties. In addition, two rounds of focused sampling were performed at selected sites to characterize short-term variations in CEC and fecal coliform concentrations, and to evaluate environmental persistence following source correction activities. The results indicate that a suite of common use compounds are suitable as generalized tracers of bacterial contamination from septic systems and that fate and transport properties are important in tracer selection. Highly recalcitrant or highly labile compounds likely follow different loss profiles in the subsurface compared to fecal bacteria and are not suitable tracers. The use of more than one tracer compound is recommended due to source variability of septic systems and to account for variations in the subsurface condition. In addition, concentrations of some CECs were measured in receiving waters at levels which suggested the potential for environmental harm, indicating that the possible risk presented from these sources warrants further investigation. PMID- 27262553 TI - Real-time monitoring of beta-d-glucuronidase activity in sediment laden streams: A comparison of prototypes. AB - Detection of enzymatic activities has been proposed as a rapid surrogate for the culture-based microbiological pollution monitoring of water resources. This paper presents the results of tests on four fully automated prototype instruments for the on-site monitoring of beta-d-glucuronidase (GLUC) activity. The tests were performed on sediment-laden stream water in the Hydrological Open Air Laboratory (HOAL) during the period of March 2014 to March 2015. The dominant source of faecal pollution in the stream was swine manure applied to the fields within the catchment. The experiments indicated that instrument pairs with the same construction design yielded highly consistent results (R(2) = 0.96 and R(2) = 0.94), whereas the results between different designs were less consistent (R(2) = 0.71). Correlations between the GLUC activity measured on-site and culture-based Escherichia coli analyses over the entire study period yielded R(2) = 0.52 and R(2) = 0.47 for the two designs, respectively. The correlations tended to be higher at the event scale. The GLUC activity was less correlated with suspended sediment concentrations than with E. coli, which is interpreted in terms of indicator applicability and the time since manure application. The study shows that this rapid assay can yield consistent results over a long period of on-site operation in technically challenging habitats. Although the use of GLUC activity as a proxy for culture-based assays could not be proven for the observed habitat, the study results suggest that this biochemical indicator has high potential for implementation in early warning systems. PMID- 27262554 TI - GPCRs in invertebrate innate immunity. AB - G-protein coupled receptors (GPCRs) represent a privileged point of contact between cells and their surrounding environment. They have been widely adopted in vertebrates as mediators of signals involved in both innate and adaptive immunity. Invertebrates rely on innate immune defences to resist infection. We review here evidence from a number of different species, principally the genetically tractable Caenorhabditis elegans and Drosophila melanogaster that points to an important role for GPCRs in modulating innate immunity in invertebrates too. In addition to examples of GPCRs involved in regulating the expression of defence genes, we discuss studies in C. elegans addressing the role of GPCR signalling in pathogen aversive behaviour. Despite the many lacunae in our current knowledge, it is clear that GPCR signalling contributes to host defence across the animal kingdom. PMID- 27262555 TI - [Severe chronic hypocalcaemia in an asymptomatic patient]. PMID- 27262556 TI - Limiting Free Pricing of New Innovative Drugs After Launch: A Necessity for Payers? PMID- 27262557 TI - Microfluidic integrated acoustic waving for manipulation of cells and molecules. AB - Acoustophoresis with its simple and low-cost fabrication, rapid and localized fluid actuation, compatibility with microfluidic components, and biocompatibility for cellular studies, has been extensively integrated into microfluidics to provide on-chip microdevices for a variety of applications in biology, bioengineering and chemistry. Among different applications, noninvasive manipulation of cells and biomolecules are significantly important, which are addressed by acoustic-based microfluidics. Here in this paper, we briefly explain the principles and different configurations of acoustic wave and acoustic streaming for the manipulation of cells and molecules and overview its applications for single cell isolation, cell focusing and sorting, cell washing and patterning, cell-cell fusion and communication, and tissue engineering. We further discuss the application of acoustic-based microfluidic systems for the mixing and transport of liquids, manipulation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules, followed by explanation on the present challenges of acoustic-based microfluidics for the handling of cells and molecules, and highlighting the future directions. PMID- 27262558 TI - Highly sensitive and selective detection of nitrite ions using Fe3O4@SiO2/Au magnetic nanoparticles by surface-enhanced Raman spectroscopy. AB - A novel and pragmatic method was developed to detect the concentration of nitrite ions using Fe3O4@SiO2/Au magnetic nanoparticles (MNPs) by surface-enhanced Raman scattering (SERS). The as-prepared bifunctional nanocomposites can be used to simultaneously purify target molecules using external magnetic field and produce Raman fingerprint spectrum with trace level of target molecules. In acidic media, 4-aminothiophenol (4-ATP) molecules conjugated on Fe3O4@SiO2/Au MNPs were triggered by nitrite ions to form azo bonds, resulting in three new marker peaks on the SERS spectrum. Under optimized conditions, the detection limit based on the three marker peaks were 15.63, 13.69, and 17.77MUM, which was much lower than the maximum NO2(-) concentration of 1.0mgL(-1) (71.4MUM) allowed in drinking water as defined by U.S. Environmental Protection Agency (EPA). The specificity of this proposed method to detect nitrite ions was demonstrated using common ions as competitors. In addition, the SERS-based technique was successfully employed to detect nitrite ions in pond water, a synthetic urine solution, and pickle brine. Considering its good sensitivity and selectivity, the detection method is well suited for the detection of nitrite ions in real samples without pretreatment steps. PMID- 27262559 TI - Effect of myopic anisometropia on anterior and posterior ocular segment parameters. AB - The purpose of this study is to investigate the differences in anterior and posterior segment parameters of more myopic eyes compared to fellow eyes using spectral domain optical coherence tomography and optical biometer device in patients with myopic anisometropia. This prospective cross-sectional study included 42 myopic anisometropic patients with and without amblyopia, aged between 7 and 40 years old. The refractive error and keratometry values, axial length (AL), central corneal thickness (CCT), peripapillary retinal nerve fiber layer thickness (RNFLT), and central macular thickness (CMT) were evaluated. Eighteen of the patients had myopic anisometropia with amblyopia, and the remaining 24 had myopic anisometropia without amblyopia. There were 23 female and 19 male patients with a mean age as 23.67 +/- 10.12 years (range 7-40). The right eyes of the subjects significantly had a higher degree of myopia. There was a significant difference in mean best-corrected visual acuity (0.195 +/- 0.234 vs. 0.011 +/- 0.025 logMAR, p < 0.001), spherical equivalent refraction (-3.95 +/- 1.38 vs. -1.04 +/- 0.99 D, p < 0.001), AL (25.06 +/- 1.27 vs. 23.99 +/- 0.98 mm, p < 0.001), and RNFLT (89.24 +/- 12.84 vs. 94.57 +/- 10.81 MUm, p < 0.001) between the more myopic and fellow eyes in all patients. On the contrary, there was no significant difference in CMT and anterior segment parameters including mean keratometry and CCT in all patients and either group. During the development of the myopic anisometropia, more myopic eyes have significantly more myopic refraction, longer AL and thinner RNFLT compared to the fellow eyes. PMID- 27262560 TI - Total en bloc spondylectomy for locally aggressive and primary malignant tumors of the lumbar spine. AB - PURPOSE: To report outcomes after total en bloc spondylectomy (TES) for primary aggressive/malignant tumors of the lumbar spine. METHODS: We performed a retrospective review of 23 neurosurgical patients operated between 2004 and 2014. Outcomes included perioperative complication rates and reoperation rates for instrumentation failure. The relationship between patient/operative parameters and complication development/instrumentation failure was investigated. RESULTS: There were 15 men (65.2 %) and eight women (24.8 %), with a median of 47 years. The most common tumor was chordoma in 11 patients (47.8 %), followed by sarcoma in four (17.4 %), and giant cell tumor in three (13.0 %). All patients but one underwent a two-staged operation; median total estimated blood loss was 3200 mL and median total operative time was 18.5 h. Fifteen patients developed at least one perioperative complication (65.2 %), with the most common being wound infection and ileus (26.1 % each). There was one case of intraoperative iliac vein injury (4.4 %). Instrumentation failure occurred in 9 patients (39.1 %) at a median time of 23 months after index spondylectomy. Following logistic regression, there were no factors associated with complication development. On the other hand, postoperative radiation was significantly associated with instrumentation failure (OR 7.49; 95 % CI, 1.02-54.9). Local recurrence and 5 year survival was 8.7 and 84.4 %, respectively. Median follow-up time was 50 months. CONCLUSIONS: Although favorable oncological outcomes after en bloc resection of spinal tumors may be achieved in terms of recurrence and survival, TES in the lumbar spine remains a challenging procedure. Future investigation into complication avoidance and reconstruction techniques is encouraged. PMID- 27262561 TI - Does surgical technique influence clinical outcome after lumbar spinal stenosis decompression? A comparative effectiveness study from the Norwegian Registry for Spine Surgery. AB - INTRODUCTION: The aim of this study was to compare the clinical outcome of spinal process osteotomy with two other midline-retaining methods, bilateral laminotomy and unilateral laminotomy with crossover, among patients undergoing surgery for lumbar spinal stenosis. METHODS: This cohort study was based on data from the Norwegian Registry for Spine Surgery (NORspine). Patients were operated on between 2009 and 2013 at 31 Norwegian hospitals. The patients completed questionnaires at admission for surgery, and after 3 and 12 months. The Oswestry Disability Index (ODI) was the primary outcome. Secondary outcomes were duration of surgery and hospital stay, Numeric Rating Scale (NRS) for back pain and leg pain, and EQ-5D and EQ-VAS. The patients were classified into one of three treatment groups according to the surgery they had received, and a propensity score was utilized to minimize bias. The three treatment groups were divided into subgroups based on Propensity Scores, and the statistical analyses were performed with and within the Propensity Score stratified subgroups. RESULTS: 103 patients had spinal process osteotomy, 966 patients had bilateral laminotomy, and 462 patients had unilateral laminotomy with crossover. Baseline clinical scores were similar in the three groups. There were no differences in improvement after 3 and 12 months between treatment groups. At 12 months, mean ODI improvement was 15.2 (SD 16.7) after spinous process osteotomy, 16.9 (SD 17.0) after bilateral laminotomy, and 16.7 (SD 16.9) after unilateral laminotomy with crossover. There were no differences in the secondary clinical outcomes or complication rates. Mean duration of surgery was greatest for spinal process osteotomy (p < 0.05). Length of stay was 2.1 days (SD 2.1) in the bilateral laminotomy group, 3.5 (SD 2.4) days for unilateral laminotomy, and 6.9 days (SD 4.1) for spinous process osteotomy group (p < 0.05). CONCLUSION: In a propensity scored matched cohort, there were no differences in the clinical outcome 12 months after surgery for lumbar spinal stenosis performed using the three different posterior decompression techniques. Bilateral laminotomy had shortest duration of surgery and shortest length of hospital stay. Surgical technique does not seem to affect clinical outcome after three different midline-retaining posterior decompression techniques. PMID- 27262563 TI - Factors Affecting Dental Attendance of Children of New Immigrant Parents: A Cross Sectional Study. AB - To explore factors affecting children's dental attendance among new immigrants. Participants in this cross-sectional study were 314 new immigrant child-parent pairs. Parents' demographics, oral health knowledge, perceptions, child's caries status, and oral health behaviours were analysed as determinants for dental attendance. Only 43 % of children had a dental visit within the year. Parents believing in the effectiveness of parental checking were four times more likely to seek dental care for their child [adjusted OR (adOR) 4.48, 95 % CI 1.79 11.13]. Parents perceiving dental check-up as a painful experience were 67 % less likely to visit the dentist (adOR 0.33, 95 % CI 0.17-0.63). Lack of insurance and time reduced the odds of a dental visit by 65 and 59 %, respectively (adOR 0.35, 95 % CI 0.16-0.68; adOR 0.41, 95 % CI 0.12-0.99). The care-seeking behaviour of new immigrant children was determined by parents' perceived ability to detect caries, availability of time and dental insurance, and their perceived dental experience. PMID- 27262562 TI - Using virtual reality to investigate psychological processes and mechanisms associated with the onset and maintenance of psychosis: a systematic review. AB - PURPOSE: In the last decade researchers have embraced virtual reality to explore the psychological processes and mechanisms that are involved in the onset and maintenance of psychosis. A systematic review was conducted to synthesise the evidence of using virtual reality to investigate these mechanisms. METHODS: Web of Science, PsycINFO, Embase, and Medline were searched. Reference lists of collected papers were also visually inspected to locate any relevant cited journal articles. In total 6001 articles were potentially eligible for inclusion; of these, 16 studies were included in the review. RESULTS: The review identified studies investigating the effect of interpersonal sensitivity, childhood bullying victimisation, physical assault, perceived ethnic discrimination, social defeat, population density and ethnic density on the real-time appraisal of VR social situations. Further studies demonstrated the potential of VR to investigate paranoid ideation, anomalous experiences, self-confidence, self-comparison, physiological activation and behavioural response. CONCLUSIONS: The reviewed studies suggest that VR can be used to investigate psychological processes and mechanisms associated with psychosis. Implications for further experimental research, as well as for assessment and clinical practise are discussed. The present review has been registered in the PROSPERO register: CRD42016038085. PMID- 27262564 TI - Antimycobacterial activity of medicinal plants used by the Mayo people of Sonora, Mexico. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tuberculosis (TB) is an infectious disease mainly caused by Mycobacterium tuberculosis (Mtb), which generates 9 million new cases worldwide each year. The Mayo ethnicity of southern Sonora, Mexico is more than 2000 years old, and the Mayos possess extensive knowledge of traditional medicine. AIMS OF THE STUDY: To evaluate the antimycobacterial activity levels of extracts of medicinal plants used by the Mayos against Mtb and Mycobacterium smegmatis (Msm) in the treatment of TB, respiratory diseases and related symptoms. MATERIALS AND METHODS: A total of 34 plant species were collected, and 191 extracts were created with n-hexane, dichloromethane, ethyl acetate (EtOAc), methanol and water. Their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined against Mtb H37Rv using the microplate alamar blue assay (MABA) and against Msm using the resazurin microplate assay (REMA) at 6 and 2 days of exposure, respectively, and at concentrations of 250-1.9ug/mL (n-hexane extracts) and 1000-7.81ug/mL (extracts obtained with dichloromethane, EtOAc, methanol and water). RESULTS: Rhynchosia precatoria (Willd.) DC. (n-hexane root extract), Euphorbia albomarginata Torr. and A. Gray. (EtOAc shoot extract) and Helianthus annuus L. (n-hexane stem extract) were the most active plants against Mtb H37Rv, with MICs of 15.6, 250, 250ug/mL and MBCs of 31.25, 250, 250ug/mL, respectively. R. precatoria (root) was the only active plant against Msm, with MIC and MBC values of >=250ug/mL. None of the aqueous extracts were active. CONCLUSIONS: This study validates the medicinal use of certain plants used by the Mayo people in the treatment of TB and related symptoms. R. precatoria, E. albomarginata and H. annuus are promising plant sources of active compounds that act against Mtb H37Rv. To our knowledge, this is the first time that their antimycobacterial activity has been reported. Crude extracts obtained with n-hexane, EtOAc and dichloromethane were the most active against Mtb H37Rv. PMID- 27262565 TI - Empathic Responses to Mother's Emotions Predict Internalizing Problems in Children of Depressed Mothers. AB - Recent theories posit that empathy, typically an adaptive characteristic, may be associated with internalizing problems when children are chronically exposed to mother's depression. We tested this postulation in a sample of children (N = 82, M age = 5 years). Children witnessed their mothers express sadness, anger, and happiness during a simulated phone conversation, and researchers rated children's negative affective empathy, positive affective empathy, and information-seeking (cognitive empathy) in response to their mother's emotions. The chronicity of mother's depression during the child's lifetime moderated associations between children's empathy and internalizing problems. As predicted, all three empathy measures were related to greater mother-rated internalizing problems in children of chronically (i.e., 2-3 years) depressed mothers. Greater positive empathy was related to lower internalizing problems in children of nondepressed mothers. Positive empathy may contribute to adaptive processes when mothers are not depressed, and positive, negative, and cognitive empathy may contribute to maladaptive processes when mothers are chronically depressed. PMID- 27262567 TI - Systematic development and optimization of chemically defined medium supporting high cell density growth of Bacillus coagulans. AB - With determined components and experimental reducibility, the chemically defined medium (CDM) and the minimal chemically defined medium (MCDM) are used in many metabolism and regulation studies. This research aimed to develop the chemically defined medium supporting high cell density growth of Bacillus coagulans, which is a promising producer of lactic acid and other bio-chemicals. In this study, a systematic methodology combining the experimental technique with flux balance analysis (FBA) was proposed to design and simplify a CDM. The single omission technique and single addition technique were employed to determine the essential and stimulatory compounds, before the optimization of their concentrations by the statistical method. In addition, to improve the growth rationally, in silico omission and addition were performed by FBA based on the construction of a medium size metabolic model of B. coagulans 36D1. Thus, CDMs were developed to obtain considerable biomass production of at least five B. coagulans strains, in which two model strains B. coagulans 36D1 and ATCC 7050 were involved. PMID- 27262566 TI - Neuropeptide Y1 receptor inhibits cell growth through inactivating mitogen activated protein kinase signal pathway in human hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers, and its incidence is increasing worldwide. Neuropeptide Y (NPY) broadly expressed in the central and peripheral nervous system. It participates in multiple physiological and pathological processes through specific receptors. Evidences are accumulating that NPY is involved in development and progression in neuro- or endocrine related cancers. However, little is known about the potential roles and underlying mechanisms of NPY receptors in HCC. In this study, we analyzed the expression of NPY receptors by real-time polymerase chain reaction, Western blot, and immunohistochemical staining. Correlation between NPY1R levels and clinicopathological characteristics, and survival of HCC patients were explored, respectively. Cell proliferation was researched by CCK-8 in vitro, and tumor growth was studied by nude mice xenografts in vivo. We found that mRNA and protein level of NPY receptor Y1 subtype (NPY1R) significantly decreased in HCC tissues. Low expression of NPY1R closely correlated with poor prognosis in HCC patients. Proliferation of HCC cells was significantly inhibited by recombinant NPY protein in vitro. This inhibitory effect could be blocked by selected NPY1R antagonist BIBP3226. Furthermore, overexpression of NPY1R could significantly inhibit HCC cell proliferation. Knockdown of NPY1R promoted cell multiplication in vitro and increased tumorigenicity and tumor growth in vivo. NPY1R was found to participate in the inhibition of cell proliferation via inactivating mitogen activated protein kinase signal pathway in HCC cells. Collectively, NPY1R plays an inhibitory role in tumor growth and may be a promising therapeutic target for HCC. PMID- 27262569 TI - Growth inhibition of S. cerevisiae, B. subtilis, and E. coli by lignocellulosic and fermentation products. AB - This paper describes the effect of several inhibiting components on three potential hosts for the bio-based production of methyl propionate, namely, wild type Escherichia coli and Bacillus subtilis, and evolved Saccharomyces cerevisiae IMS0351. The inhibition by the lignocellulose-derived products 5-hydroxymethyl-2 furaldehyde, vanillin, and syringaldehyde and the fermentation products 2 butanol, 2-butanone, methyl propionate, and ethyl acetate has been assessed for these strains in defined medium. Multiple screenings were performed using small scale cultures in both shake flasks and microtiter plates. Technical drawbacks revealed the limited applicability of the latter in this study. The microbial growth was characterized by means of a lag-time model, and the inhibitory thresholds were determined using product-inhibition models. The lignocellulose derived products were found to be highly inhibitory, and none of the strains could grow in the presence of 2.0 g L-1 of product. From the fermentation products tested, methyl propionate had the most severe impact resulting in complete inhibition of all the strains when exposed to concentrations in the range of 12-18 g L-1. In general, S. cerevisiae and B. subtilis were comparatively more tolerant than E. coli to all the fermentation products, despite E. coli's lower sensitivity towards vanillin. The results suggest that, overall, the strains investigated have good potential to be engineered and further established as hosts for the bio-based production of methyl esters. PMID- 27262571 TI - [Fulminant sepsis due to Ralstonia pickettii]. PMID- 27262570 TI - Neuroendocrine carcinoma of the pancreas with similar genetic alterations to invasive ductal adenocarcinoma. AB - Neuroendocrine carcinoma (NEC) of the pancreas is very rare, and its origin is not fully elucidated. Here, we present a case of a small-size NEC of the pancreas that is genetically similar to invasive ductal adenocarcinoma (IDA). A 65-year old man was referred to our hospital due to obstructive jaundice and found to have a 12-mm solid tumor in the pancreas head. The tumor exhibited low vascularity on enhanced computed tomography, and endoscopic retrograde pancreatographic imaging revealed an irregular obstruction in a branch duct of the pancreas. The patient was thereby diagnosed with a pancreatic ductal cancer, and stomach-preserving pancreaticoduodenectomy with regional lymph node resection was performed. Histochemical analysis of the resected tumor showed that the neoplastic cells with scanty cytoplasm and hyperchromatic nuclei strongly expressed chromogranin A and synaptophysin. The Ki-67 index was 40 % in the most proliferative tumor regions, and the tumor was diagnosed as a NEC of the pancreas. However, in the analysis of genetic alterations of the tumor tissue, the neoplastic cells showed altered KRAS, TP53, and SMAD4/DPC4, suggesting that the NEC in our case is genetically related to IDA. Our data suggest that poorly differentiated IDAs may transform into NECs. PMID- 27262568 TI - Persisters-as elusive as ever. AB - Persisters-a drug-tolerant sub-population in an isogenic bacterial culture-have been featured throughout the last decade due to their important role in recurrent bacterial infections. Numerous investigations detail the mechanisms responsible for the formation of persisters and suggest exciting strategies for their eradication. In this review, we argue that the very term "persistence" is currently used to describe a large and heterogeneous set of physiological phenomena that are functions of bacterial species, strains, growth conditions, and antibiotics used in the experiments. We caution against the oversimplification of the mechanisms of persistence and urge for a more rigorous validation of the applicability of these mechanisms in each case. PMID- 27262572 TI - [Urinary infection due to Mycobacterium fortuitum in a patient with HIV infection]. PMID- 27262573 TI - [Myeloradiculitis due to Epstein-Barr virus reactivation in a Hodgkin's lymphoma patient]. PMID- 27262574 TI - The validity of the Satisfaction with Life Scale in adolescents and a comparison with single-item life satisfaction measures: a preliminary study. AB - PURPOSE: The validity of the life satisfaction measures commonly used among adults has been rarely examined in adolescent samples. The present research had two main goals: (1) to evaluate the structural validity of the Satisfaction with Life Scale (SWLS) among adolescents and to test measurement invariance across gender; (2) to compare the criterion and convergent validity of the SWLS and single-item life satisfaction measures among adolescents. METHODS: Three samples of Serbian adolescents were recruited for the present research. Study 1 (N = 481, M age = 17.01 years) examined the structure of the SWLS via confirmatory factor analysis (CFA) and evaluated measurement invariance of the SWLS across gender by a multi-group CFA. Study 2 (N = 283, M age = 17.34 years) and Study 3 (N = 220, M age = 16.73 years) compared the convergent validity of the SWLS and single-item life satisfaction measures. RESULTS: The results of Study 1 supported the original one-factor model of the SWLS among adolescents and provided evidence for strong measurement invariance of the SWLS across gender. The findings of Study 2 and Study 3 showed that the SWLS and single-item measures were equally valid and strongly associated (r = .734 in Study 2 and r = .668 in Study 3). No substantial differences in correlations with school success and well-being indicators were found between the SWLS and single-item measures. CONCLUSIONS: Our findings support the use of the SWLS among adolescents and indicate that single-item life satisfaction measures perform as well as the SWLS in adolescent samples. PMID- 27262575 TI - Molecular dynamics study of the behavior of nitromethanes enclosed inside carbon nanotube containers. AB - We utilized molecular dynamics (MD) to investigate the behavior of nitromethane molecules (NMs) enclosed inside carbon nanotube (CNT) containers sealed with buckybowl caps. Two different sizes of CNT containers, i.e., (10,10) and (20,20), were employed to contain the energetic NMs. After loading the NMs into these containers, MD simulations were carried out at different loading densities. The loading density was changed from 0.4 to 2.0 g/cc. At low loading densities, NMs preferentially resided near the surface of the CNT wall (orienting themselves in the cylindrical direction) and near the buckybowl caps (orienting themselves in the principal-axis direction). This behavior suggests the buckybowl caps and the CNT wall have attractive interactions with the NMs. The distribution of the NMs inside the containers did not change upon increasing the temperature from ambient to 100 degrees C. However, the positional preference of the NMs found at ambient temperature to 100 degrees C was not the same as that observed at 1000 degrees C due to the increased thermal motions of the NMs. The size of the CNT container had a significant effect on the fluidity of the NMs. From 25 to 100 degrees C, the NMs inside the (10,10) CNT container were only mobile at low loading densities. On the other hand, in the (20,20) CNT container, the NMs showed good mobility up to a loading density of 1.6 g/cc. Graphical Abstract Attractive interactions between the nitromethanes and the buckybowl caps as well as the carbon nanotube wall. PMID- 27262576 TI - Modeling prepolymerization step of a serotonin imprinted polymer. AB - Studies on generating artificial macromolecular receptors by molecular imprinting of synthetic polymers significantly emerged in the literature during last decades. The non-covalent approach, one of the three methods used in MIP synthesis, is more flexible for the choice of functional monomers, possible target molecules, and use of the imprinted materials. This study aims to investigate a serotonin imprinted polymer prepared by non-covalent approach using molecular modeling. The calculations were carried out by using density functional theory at omegaB97XD/6-31++G(d,p) level and the polarizable continuum model was used for solvent calculations. Computational results showed that DMSO plays an important role in the MIP formation as it seems to control the size and the shape of the cavity. DMSO performs these tasks through hydrogen bonding and dispersive interactions. Although experimental IR could not verify the specific interaction modes because of broadband structure, computational IR results showed these modes clearly indicating the interactions leading to MIP formation. This model is specific to the studied serotonin-acrylamide-DMSO system but further studies may reveal a general computational protocol for other MIP systems. PMID- 27262577 TI - Placement of integrated self-expanding Y-shaped airway stent in management of carinal stenosis. AB - PURPOSE: To investigate the feasibility and effectiveness of integrated self expanding Y-shaped airway stent placement for patients with carinal stenosis. MATERIALS AND METHODS: From May 2010 to March 2015, 12 consecutive patients with carinal stenosis, treated by placement of integrated self-expanding Y-shaped airway stent, were included this retrospective study. Data on technical success, clinical success, and follow-up were analyzed. RESULTS: Technical success was 100 %. Eleven uncovered stents and one covered stent placed in 12 patients. Eleven patients underwent stent insertion under local pharyngeal anesthesia, and one patient underwent stent insertion under general anesthesia. Clinical success was 100 %. The respiratory difficulty improved instantly after treatment. The average Hugh-Jones classification grade and arterial oxygen saturation improved from 4.3 +/- 0.6 and 83.0 +/- 2.6 % before treatment to 1.4 +/- 0.5 (p < 0.001) and 95.4 +/- 1.2 % (p < 0.001) after treatment, respectively. During 3-15 months (mean 6.5 +/- 3.3 months) of follow-up, two patients experienced the re-stenosis of the stent 75 and 78 days after treatment. All patients died during the follow-up. Survival after stent insertion ranged from 96 to 432 days (median 165 days). The cumulative 6- and 12-month survival rates were 41.7 and 8.3 %, respectively. CONCLUSIONS: Placement of integrated self-expanding Y-shaped airway stent is a simple, safe, and effective method for patients with carinal stenosis. PMID- 27262578 TI - Magnetic resonance imaging appearance of oxidized regenerated cellulose in breast cancer surgery. AB - PURPOSE: To describe magnetic resonance imaging (MRI) findings in patients who underwent breast-conserving surgery followed by oxidized regenerated cellulose (ORC) implantation in surgical cavity. MATERIALS AND METHODS: We retrospectively reviewed 51 MRI examinations performed between January 2009 and January 2014 in 51 patients who underwent BCS with ORC implantation. RESULTS: In 29/51 (57 %) cases, MRIs showed abnormal findings with three main MRI patterns: (1) complex masses: hyperintense collections on T2-weighted (w) images with internal round hypointense nodules without contrast enhancement (55 %); (2) completely hyperintense collections (17 %); and (3) completely hypointense lesions (28 %). All lesions showed rim enhancement on T1w images obtained in the late phase of the dynamic study with a type 1 curve. Diffusion-weighted imaging was negative in all MRIs and, in particular, 22/29 (76 %) lesions were hyperintense but showing ADC values >1.4 * 10(-3) mm(2)/s, while the remaining 7/29 (24 %) lesions were hypointense. In four cases, linear non-mass-like enhancement was detected at the periphery of surgical cavity; these patients were addressed to a short-term follow-up, and the subsequent examinations showed the resolution of these findings. CONCLUSION: When applied to surgical residual cavity, ORC can lead alterations in surgical scar. This could induce radiologists to misinterpret ultrasonographic and mammographic findings, addressing patients to MRI or biopsy; so knowledge of MRI specific features of ORC, it is essential to avoid misdiagnosis of recurrence. PMID- 27262579 TI - Pre-surgical assessment of mandibular bone invasion from oral cancer: comparison between different imaging techniques and relevance of radiologist expertise. AB - PURPOSE: To compare diagnostic performance between computed tomography (CT) and magnetic resonance imaging (MRI) for the detection of bone infiltration from oral cancer, and to test interobserver agreement between radiologists with different expertises. MATERIALS AND METHODS: Pre-surgical CT and MRI were reviewed independently by two radiologists with different expertises in head and neck oncology. A third radiologist reviewed CT and MRI simultaneously. Interobserver agreement was calculated by Cohen test. Association between radiological evidence of bone infiltration and histological reference was tested by Fisher's exact test or Chi-squared test, as appropriate. Receiving operator curve was calculated and area under the curve (AUC) was compared between CT, MRI, and both methods together. RESULTS: Interobserver agreement was moderate: the trainee under reported periosteal reaction on CT and inferior alveolar canal involvement on MRI. Imaging findings associated with histologic evidence of bone infiltration were: periosteal reaction and cortical erosion on CT; bone marrow involvement, contrast enhancement within bone; and inferior alveolar canal involvement on MRI. Sensitivity of MRI alone (74 %) was higher than CT (52 %). Simultaneous review of CT and MRI showed the highest specificity (91 %), with the increase of diagnostic performance in the subgroup of subjects with positive MRI (AUC = 0.689; p = 0.044). CONCLUSION: Higher expertise allows pre-surgical detection of clinically relevant signs of bone infiltration sensitivity of MRI alone is higher than CT for the detection of bone infiltration from oral cancer. In MRI positive cases, diagnostic integration with combined review of CT and MRI is suggested for optimal diagnostic performance. PMID- 27262581 TI - Multiple roles of the general regulatory factor Abf1 in yeast ribosome biogenesis. AB - In Saccharomyces cerevisiae, the large majority of the genes coding for cytoplasmic ribosomal proteins (RPs) depend on the general regulatory factor Rap1 for their transcription, but a small cohort of them relies on Abf1 regulatory activity. A recent study showed that unlike Rap1, whose association with RP gene promoters is not affected by environmental changes causing RP gene repression/reactivation, Abf1 association with both RP gene and ribosome biogenesis (Ribi) gene promoters dynamically responds to changes in growth conditions. This observation changes the paradigm of general regulatory factors as relatively static DNA-binding proteins constitutively bound to highly active promoters, and point to Abf1, which binds hundreds of non-RPG promoters within the yeast genome, as a possible key regulatory switch in nutrient- and stress dependent transcriptional modulation. Moreover, the frequent presence of Abf1 binding sites in the promoters of mitochondrial RP genes evokes the possibility that Abf1 might orchestrate still unexplored levels of co-regulation involving growth-related gene networks in yeast cells. PMID- 27262580 TI - Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study. AB - PURPOSE: This study compared measured physical performance, health-related quality of life (HRQOL), and social role attainment between extremity sarcoma survivors and controls, and evaluated associations between disease and treatment exposures, health conditions, and performance measures. METHODS: Survivors of extremity sarcoma from the St. Jude Lifetime cohort and controls frequency matched by age-, sex-, and race completed physical performance testing and questionnaires. Survivors with Z-scores on outcome measures <= -2.0 SD (compared to controls) were categorized with severe impairment/limitation. RESULTS: Among 206 survivors (52.4 % male median age 36 years (range 19-65)), 37 % had low relative lean mass, 9.7 % had an ejection fraction <50 %, 51.5 % had diffusion capacity for carbon monoxide <75 %, 27.7 % had sensory and 25.2 % motor neuropathy, and 78.2 % had musculoskeletal complications. Severe impairments/limitations were present among >=25 % of survivors on fitness, balance, and physical HRQOL measures, and among >=15 % on strength and activity of daily living measures. Lower extremity tumor location (OR 8.23, 95 % CI 2.54 26.67, P value 0.0004) and amputation (OR 8.07, 95 % CI 3.06-21.27, P value <0.0001) were associated with poor fitness. Poor fitness was associated with increased odds of scoring <40 on the SF-36 physical component summary (OR 4.83, 95 % CI 1.95-11.99, P value 0.001) and role-physical subscale (OR 3.34, 95 % CI 1.33-8.43, P value 0.01). Survivors and controls had similar rates of marriage, independent living, employment, and college attendance. CONCLUSIONS: Extremity sarcoma survivors experience high rates of physical impairment and report lower than expected physical HRQOL. However, they are as likely as peers to be married, live independently, be employed, and attend college. IMPLICATIONS FOR CANCER SURVIVORS: Follow-up for extremity sarcoma survivors should include assessment of need for further orthopedic care and rehabilitation to address cardiopulmonary and musculoskeletal health. PMID- 27262582 TI - Light-exposed shoots of seven coexisting deciduous species show common photosynthetic responses to tree height. AB - Functional traits of light-exposed leaves have been reported to show tree height dependent change. However, it remains unknown how plastic response of leaf traits to tree height is linked with shoot-level carbon gain. To answer this question, we examined the photosynthetic properties of fully lit current-year shoots in crown tops with various heights for seven deciduous broad-leaved species dominated in a cool-temperate forest in northern Japan. We measured leaf mass, stomatal conductance, nitrogen content, light-saturated net photosynthetic rate (all per leaf lamina area), foliar stable carbon isotope ratio, and shoot mass allocation to leaf laminae. We employed hierarchical Bayesian models to simultaneously quantify inter-trait relationships for all species. We found that leaf and shoot traits were co-varied in association with height, and that there was no quantitative inter-specific difference in leaf- and shoot-level plastic responses to height. Nitrogen content increased and stomatal conductance decreased with height. Reflecting these antagonistic responses to height, photosynthetic rate was almost unchanged with height. Photosynthetic rate divided by stomatal conductance as a proxy of photosynthetic water use efficiency sufficiently explained the variation of foliar carbon isotope ratio. The increase in mass allocation to leaves in a shoot compensated for the height-dependent decline in photosynthetic rate per leaf lamina mass. Consequently, photosynthetic gain at the scale of current-year shoot mass was kept unchanged with tree height. We suggest that the convergent responses of shoot functional traits across species reflect common requirements for trees coexisting in a forest. PMID- 27262583 TI - Habitat moisture is an important driver of patterns of sap flow and water balance in tropical montane cloud forest epiphytes. AB - Microclimate in the tropical montane cloud forest (TMCF) is variable on both spatial and temporal scales and can lead to large fluctuations in both leaf-level transpiration and whole plant water use. While variation in transpiration has been found in TMCFs, the influence of different microclimatic drivers on plant water relations in this ecosystem has been relatively understudied. Within the TMCF, epiphytes may be particularly affected by natural variation in microclimate due to their partial or complete disassociation from soil resources. In this study, we examined the effects of seasonal microclimate on whole plant water balance in epiphytes in both an observational and a manipulative experiment. We also evaluated the effects of different microclimatic drivers using three hierarchical linear (mixed) models. On average, 31 % of total positive sap flow was recovered via foliar water uptake (FWU) over the course of the study. We found that precipitation was the greatest driver of foliar water uptake and nighttime sap flow in our study species and that both VPD and precipitation were important drivers to daytime sap flow. We also found that despite adaptations to withstand seasonal drought, an extended dry period caused severe desiccation in most plants despite a large reduction in leaf-level and whole plant transpiration. Our results indicate that the epiphytes studied rely on FWU to maintain positive water balance in the dry season and that increases in dry periods in the TMCF may be detrimental to these common members of the epiphyte community. PMID- 27262584 TI - Enhancement of Lipid Production of Chlorella Pyrenoidosa Cultivated in Municipal Wastewater by Magnetic Treatment. AB - Despite the significant breakthroughs in research on microalgae as a feedstock for biodiesel, its production cost is still much higher than that of fossil diesel. One possible solution to overcome this problem is to optimize algal growth and lipid production in wastewater. The present study examines the feasibility of using magnetic treatment for enhancement of algal lipid production and wastewater treatment in outdoor-cultivated Chlorella pyrenoidosa. Results confirmed that magnetic treatment significantly enhances biomass and lipid productivity of C. pyrenoidosa by 12 and 10 %, respectively. Application of magnetic field in a semi-continuous culture resulted in highly treated wastewater with total nitrogen maintained under 15 mg L-1, ammonia nitrogen below 5 mg L-1, total phosphorus less than 0.5 mg L-1, and CODCr less than 50 mg L-1. In addition, magnetic treatment resulted in a decrease of wastewater turbidity, an increase of bacterial numbers, and an increase of active oxygen in wastewater which might be attributed to the enhancement of growth and lipid production of C. pyrenoidosa. PMID- 27262585 TI - SATB2 is expressed in Merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is a rare aggressive skin cancer with neuroendocrine differentiation. With immunohistochemistry, the tumor cells stain for both neuroendocrine (i.e., synaptophysin and chromogranin A) and epithelial markers. The epithelial marker cytokeratin 20 (CK20) stains positive with immunohistochemistry in a vast majority of MCCs. The expression of the special AT rich sequence-binding protein (SATB2) was analyzed in MCC (n = 20) together with other forms of skin cancer and neuroendocrine tumors (n = 51) using immunohistochemistry. The results were compared to the expression of CK20, synaptophysin, and chromogranin A. The majority of the MCCs stained positive for synaptophysin and chromogranin A (95 vs 80 % respectively), and 75 % of the MCCs showed cytoplasmic positivity for CK20 and nuclear positivity for SATB2, with two discordant cases lacking expression of one of these markers. We conclude that immunohistochemistry for SATB2 can be used as an additional marker with similar sensitivity and specificity as CK20 for the diagnosis of Merkel cell carcinoma, suggesting a clinical utility in difficult cases where MCC is suspected. PMID- 27262586 TI - Low levels of glutathione are sufficient for survival of keratinocytes after UV irradiation and for healing of mouse skin wounds. AB - Reduced levels of the cellular antioxidant glutathione are associated with premature skin aging, cancer and impaired wound healing, but the in vivo functions of glutathione in the skin remain largely unknown. Therefore, we analyzed mice lacking the modifier subunit of the glutamate cysteine ligase (Gclm), the enzyme that catalyzes the rate-limiting step of glutathione biosynthesis. Glutathione levels in the skin of these mice were reduced by 70 %. However, neither skin development and homeostasis, nor UVA- or UVB-induced apoptosis in the epidermis were affected. Histomorphometric analysis of excisional wounds did not reveal wound healing abnormalities in young Gclm deficient mice, while the area of hyperproliferative epithelium as well as keratinocyte proliferation were affected in aged mice. These findings suggest that low levels of glutathione are sufficient for wound repair in young mice, but become rate-limiting upon aging. PMID- 27262587 TI - A Curious Case of Inhalation Fever Caused by Synthetic Cannabinoid. AB - BACKGROUND: This case report describes inhalation fever as an uncommon pulmonary adverse effect of synthetic cannabinoids. CASE REPORT: A 29-year-old man was brought in for severe agitation after smoking K2, a synthetic cannabinoid. He required multiple doses of lorazepam and haloperidol for sedation. His vital signs were notable for a mild fever and tachycardia. Otherwise, the rest of his exam was unremarkable. The laboratory test was significant for leucocytosis and diffuse reticular-nodular and interstitial infiltrates on chest radiograph. Urine drug toxicology was negative. Interestingly, his symptoms and pulmonary infiltrates on the chest radiograph resolved spontaneously after 24 hours of observation. CONCLUSIONS: This patient developed transient pulmonary infiltrates and fever following the synthetic cannabinoid inhalation, as seen in self limiting inhalation fever. Inhalation fever as a consequence of synthetic cannabinoid has not been described previously and there is a need for further research in this field. PMID- 27262588 TI - Extensive investigation of the sap flow of maize plants in an oasis farmland in the middle reach of the Heihe River, Northwest China. AB - A better understanding of the sap flow characteristics of maize plants is critical for improving irrigation water-use efficiency, especially for regions facing water resource shortages. In this study, sap flow rates, related soil physics and plant-growth parameters, and meteorological factors, were simultaneously monitored in a maize field in two consecutive years, 2011 and 2012, and the sap flow rates of the maize plants were extensively analyzed based on the monitored data. Seasonal and daily variational characteristics were identified at different growth stages and under different weather conditions, respectively. The analyses on the relationships between sap flow rate and reference evapotranspiration (ET0), as well as several plant-growth parameters, indicate that the irrigation schedule can exert an influence on sap flow, and can consequently affect crop yield. The ranking of the main meteorological factors affecting the sap flow rate was: net radiation > air temperature > vapor pressure deficit > wind speed. For a quick estimation of sap flow rates, an empirical formula based on the two top influencing factors was put forward and verified to be reliable. The sap flow rate appeared to show little response to irrigation when the water content was relatively high, implying that some of the irrigation in recent years may have been wasted. These results may help to reveal the bio physical processes of maize plants related to plant transpiration, which could be beneficial for establishing an efficient irrigation management system in this region and also for providing a reference for other maize-planting regions. PMID- 27262589 TI - Identifying sex in non-fertile individuals of the moss Drepanocladus turgescens (Bryophyta: Amblystegiaceae) using a novel molecular approach. AB - Sex identification before sexual maturity is notoriously difficult in plants with separate sexes, but is crucial to address many life history related issues. To study the performance of the two sexes in the rarely sexually reproducing dioecious moss Drepanocladus turgescens a molecular sex marker is needed. The female-targeting marker previously developed for D. trifarius and D. lycopodioides amplifies for a few D. turgescens males, which can thus not be distinguished from females. In a significant addition to the earlier developed method we sequenced the portion successfully amplified by the primers PT-3f and PT-3r for six females and three males. Differences between males and females were revealed at five sequence positions. Examination of a total of fourteen females and seven marker amplifying males confirm that females and such males differ consistently at these positions. The usefulness of a previous protocol for moss sex identification is thus extended to another dioecious moss by the addition of a step where a portion of the sex-correlated region is sequenced. PMID- 27262590 TI - Magnitude of negative interpretation bias depends on severity of depression. AB - The present study investigated the hypothesis that the magnitude of negative interpretation bias displayed by those with depression is related to the degree of depression they experience. Seventy one depressed participants (scoring 14 and above on the Beck Depression Inventory II) completed tasks spanning three domains of possible negative interpretations: semantic ambiguity; nonverbal ambiguity and situational ambiguity. Regression analyses revealed that just under half of the variance in depressive symptom severity was explained by the combination of negative interpretation bias tasks, with the strongest predictor of depressive symptom severity being negative interpretation of semantic ambiguity when reading ambiguous text descriptions. Subsidiary group analyses confirmed that severely depressed individuals interpreted emotionally ambiguous information in a more negative way than did their mildly or moderately depressed counterparts. These findings indicate that the degree of negative interpretive bias is closely related to depression severity and that bias manifests especially strongly at the most severe levels of depression. Our findings may help us to refine cognitive theories of depression and be helpful in guiding therapy. PMID- 27262591 TI - New generation indirect calorimeters for measuring energy expenditure in the critically ill: a rampant or reticent revolution? AB - To lower the risk of incorrectly feeding critically ill patients, indirect calorimetry (IC) is proposed as the most ideal method to evaluate energy expenditure and to establish caloric goals. New IC devices are progressively introduced but validation of this new generation remains challenging and arduous. PMID- 27262592 TI - Absence of ALK and MET alterations in head and neck sarcomatoid carcinoma. PMID- 27262593 TI - Medical Student Presyncope and Syncope in the Operating Room: A Mixed Methods Analysis. AB - OBJECTIVE: Medical students often feel faint (presyncopal) in the operating room (OR). Despite mandatory surgical rotations in clerkship, there is little formal training and acclimatization to the operating suite in the first 2 years of medical school. This study aimed to assess presyncope and syncope in the OR in first, second, third, and fourth year medical students at a large Canadian academic center. DESIGN: Following an extensive literature review, we developed a mixed methods survey de novo to assess medical students' experience in the OR and determine the frequency of presyncopal and syncopal events. RESULTS: A total of 180 students (106 females, 59%), evenly distributed among all 4 years of medical school, responded to the survey (response rate 40%, n = 180/454). In total, 75 students (42%) had experienced presyncope, and 10 students (6%) had experienced syncope in the OR. Female medical students were more likely to experience both presyncope (p < 0.001) and syncope (p = 0.011) relative to their male colleagues. They were also more likely to report that these experiences had an effect on their attitude toward the OR (p < 0.001) and their career choice (p < 0.001). Half of respondents believed that the undergraduate medical preclerkship curriculum did not provide adequate exposure to the OR. Students consistently expressed the desire for more preclinical OR exposure and formal instruction concerning OR etiquette. Only 28% of students reported receiving information on how to avoid syncope, and their classmates were the number one source (59%) for this advice. The most commonly employed preventative measures were eating before the OR and staying well hydrated. Presyncope had a negative effect on attitudes toward the OR in 28% of students. CONCLUSION: Although true loss of consciousness (syncope) among medical students in the OR is uncommon, presyncope is a highly prevalent phenomenon. It is most prevalent in female students, and may have a negative effect on overall student well-being. All students may benefit from normalization of this very common experience by staff surgeons or residents. Formal instruction regarding the common symptoms, triggers, and methods for preventing presyncope and syncope is an essential supplement to the current preclinical medical curriculum. PMID- 27262594 TI - Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers. AB - BACKGROUND AND AIMS: Nalmefene has been approved in Europe for the treatment of alcohol dependence and subsequently recommended by the UK National Institute for Health and Care Excellence (NICE). This study examines critically the evidence base underpinning both decisions and the issues arising. METHODS: Published studies of nalmefene were identified through a systematic search, with documents from the European Medicines Agency, the NICE appraisal and public clinical trial registries also examined to identify methodological issues. RESULTS: Efficacy data used to support the licensing of nalmefene suffer from risk of bias due to lack of specification of a priori outcome measures and sensitivity analyses, use of post-hoc sample refinement and the use of inappropriate comparators. Despite this, evidence for the efficacy of nalmefene in reducing alcohol consumption in those with alcohol dependence is, at best, modest, and of uncertain significance to individual patients. The relevance of existing trial data to routine primary care practice is doubtful. CONCLUSIONS: Problems with the registration, design, analysis and reporting of clinical trials of nalmefene did not prevent it being licensed and recommended for treating alcohol dependence. This creates dilemmas for primary care clinicians and commissioning organisations where nalmefene has been heavily promoted, and poses wider questions about the effectiveness of the medicines regulation system and how to develop the alcohol treatment evidence base. PMID- 27262595 TI - Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft. AB - Tyrosyl-DNA phosphodiesterase 2 (TDP2) processes protein/DNA adducts resulting from abortive DNA topoisomerase II (Top2) activity. TDP2 inhibition could provide synergism with the Top2 poison class of chemotherapeutics. By virtual screening of the NCI diversity small molecule database, we identified selective TDP2 inhibitors and experimentally verified their selective inhibitory activity. Three inhibitors exhibited low-micromolar IC50 values. Molecular dynamics simulations revealed a common binding mode for these inhibitors, involving association to the TDP2 DNA-binding cleft. MM-PBSA per-residue energy decomposition identified important interactions of the compounds with specific TDP2 residues. These interactions could provide new avenues for synthetic optimization of these scaffolds. PMID- 27262596 TI - Investigation of the apoptotic pathway induced by benzimidazole-oxindole conjugates against human breast cancer cells MCF-7. AB - In our previous studies, benzimidazole-oxindole conjugates were synthesized and evaluated by National Cancer Institute (NCI) for their cytotoxic activity and the new molecules like 5c and 5p were considered as potential leads. These conjugates arrested the cell cycle at G2/M phase and inhibited tubulin polymerization. These observations prompted us to investigate the apoptotic mechanism induced by these lead molecules against human breast cancer cells (MCF-7). Studies like measurement of mitochondrial membrane potential (DeltaPsim), generation of reactive oxygen species (ROS) and Annexin V-FITC assay revealed that these compounds induced mitochondrial mediated (intrinsic apoptotic pathway) apoptosis in human breast cancer cells. It was further confirmed by western blot analysis of pro apoptotic protein Bax, anti apoptotic protein Bcl-2, cytochrome c release, caspase-9 activity and cleavage of PARP. PMID- 27262597 TI - Gastroprotective effects of new diterpenoid derivatives from Azorella cuatrecasasii Mathias & Constance obtained using a beta-cyclodextrin complex with microbial and chemical transformations. AB - Mulinane diterpenoids isolated from Azorella species have displayed gastroprotective effects in animal models. In this study we have transformed the main constituent, mulin-11,13-dien-20 oic acid from this plant using the filamentous fungus Mucor plumbeus and a beta-cyclodextrin inclusion complex and we have obtained two main products with good yields (33% and 15% for compound 4 and 5, respectively) for further preparation of semisynthetic derivatives to evaluate their gastroprotective effects. In addition, one of the compounds isolated from Azorella cuatrecasasii was new (9-epi-13alpha-hydroxymulinene 1). Six new derivatives 4a-4c and 5a-5c were then prepared by simple chemical transformations. The structures of all compounds were elucidated by spectroscopic means based on 1D and 2D-NMR techniques. Some 8 diterpenes were evaluated for their gastroprotective effects in the ethanol/HCl-induced ulcer model in mice at 20mg/kg. The highest gastroprotective activity was shown by 7alpha,16 dihydroxymulin-11,13-dien-20-oic acid 5, which was higher than the reference drug lansoprazole, while 16-hydroxymulin-11,13-dien-20-oic acid 4 was as active as lansoprazole. PMID- 27262598 TI - An alternative route to the arylvinyltriazole nucleosides. AB - A new pathway to synthesis of arylvinyl ribavirin analogues is developed which makes it possible to obtain not only trans- but also cis-isomers at vinyl bond. By this route eight ribavirin 5-arylvinyl analogues are synthesized and their antiviral activity is evaluated. PMID- 27262599 TI - Design, synthesis and anti-cancer activity evaluation of podophyllotoxin norcantharidin hybrid drugs. AB - In this study, we designed and synthesized eighteen podophyllotoxin norcantharidin hybrid drugs which could exhibit more potent anti-cancer activity than the parent drugs. Through the anti-proliferation assay, the most potent anti cancer agent was screened out, namely Q9 (IC50=0.88+/-0.18MUM against MCF-7 cell line), and it showed lower cytotoxicity against non-cancer cells, human embryonic kidney cells (293T) (IC50=54.38+/-3.78MUM). Additionally, based on the flow cytometry analysis result, it can cause a remarkable cell cycle arrest at G2/M phase and induce apoptosis in MCF-7 cells more significantly than podophyllotoxin or norcantharidin per se. Moreover, the expression of cell cycle relative protein CDK1 was up regulated while a protein required for mitotic initiation, Cyclin B1 was down regulated. Furthermore, according to the confocal microscopy observation results, it was shown that Q9 was a potent tubulin polymerization inhibitor and the effect is comparable to that of colchicine. For further investigation on the aforementioned mechanisms, we performed western blot experiments, thus finding the increase of the cleavage of PARP. Consistent with these new findings, molecular docking observations suggested that compound Q9 could be developed as a potential anticancer agent. PMID- 27262600 TI - Synthesis, antitumor activity and mechanism of action of novel 1,3-thiazole derivatives containing hydrazide-hydrazone and carboxamide moiety. AB - A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory activity than that of 5-Fu against MCF-7, HepG2, BGC-823, Hela, and A549 cell lines. Especially, T1, T26 and T38 exhibit best cytotoxic activity with IC50 values of 2.21MUg/mL, 1.67MUg/mL and 1.11MUg/mL, against MCF-7, BCG-823, and HepG2 cell lines, respectively. These results suggested that the combination of 1,3-thiazole, hydrazide-hydrazone, and carboxamide moiety was much favorable to cytotoxicity activity. Furthermore, the flow cytometry analysis revealed that compounds T1 and T38 could induce apoptosis in HepG2 cells, and it was confirmed T38 led the induction of cell apoptosis by S cell-cycle arrest. PMID- 27262602 TI - Provider familiarity with specialty society guidelines for risk stratification and management of patients with febrile neutropenia. PMID- 27262601 TI - Gap Junction Blockers: An Overview of their Effects on Induced Seizures in Animal Models. AB - BACKGROUND: Gap junctions are clusters of intercellular channels allowing the bidirectional pass of ions directly into the cytoplasm of adjacent cells. Electrical coupling mediated by gap junctions plays a role in the generation of highly synchronized electrical activity. The hypersynchronous neuronal activity is a distinctive characteristic of convulsive events. Therefore, it has been postulated that enhanced gap junctional communication is an underlying mechanism involved in the generation and maintenance of seizures. There are some chemical compounds characterized as gap junction blockers because of their ability to disrupt the gap junctional intercellular communication. OBJECTIVE: Hence, the aim of this review is to analyze the available data concerning the effects of gap junction blockers specifically in seizure models. RESULTS: Carbenoxolone, quinine, mefloquine, quinidine, anandamide, oleamide, heptanol, octanol, meclofenamic acid, niflumic acid, flufenamic acid, glycyrrhetinic acid and retinoic acid have all been evaluated on animal seizure models. In vitro, these compounds share anticonvulsant effects typically characterized by the reduction of both amplitude and frequency of the epileptiform activity induced in brain slices. In vivo, gap junction blockers modify the behavioral parameters related to seizures induced by 4-aminopyridine, pentylenetetrazole, pilocarpine, penicillin and maximal electroshock. CONCLUSION: Although more studies are still required, these molecules could be a promising avenue in the search for new pharmaceutical alternatives for the treatment of epilepsy. PMID- 27262603 TI - Discontinuing oral anti-coagulants in a patient with a cardiac valve prosthesis after a traumatic intracranial hemorrhage. PMID- 27262604 TI - Surfing USA: an epidemiological study of surfing injuries presenting to US EDs 2002 to 2013. AB - INTRODUCTION: Surfing is a popular recreational and competitive sport in the United States and worldwide. Previous studies indicate surfers are frequently injured, but most studies are survey based, and little is known about surfing injuries that present to emergency departments (EDs). AIMS: This study examines the epidemiology of surfing injuries presenting to US EDs. METHODS: A retrospective analysis was performed using data from the National Electronic Injury Surveillance System database from the US Consumer Product Safety Commission from 2002 to 2013. RESULTS: A total of 2072 cases were analyzed, corresponding to a national estimate of 131 494 total injuries over the 12-year period (95% confidence interval, 34 515-228 473). The median age of included cases was 27 years (interquartile range, 19-37). Lower extremity injuries were most common (25.9%), followed by the face (23.1%) and head and neck (22.7%). Lacerations were the most common injury type (40.7%), followed by sprains and strains (14.4%), contusions (12.9%), and fractures (11.9%); 95.7% of cases were treated and released. Patients older than 60 years, those injured to the trunk, and those suffering fractures or internal organ injuries were admitted at a statistically significant increased frequency (P<.05). CONCLUSION: Surfing injuries are common but rarely serious. The injuries most commonly affect the lower extremity, head, neck, and face and are most frequently lacerations. Age older than 60 years, injuries to the trunk, and internal organ injuries were associated with a statistically significant increased frequency of hospital admission. PMID- 27262606 TI - Association of adverse childhood experiences with shaking and smothering behaviors among Japanese caregivers. AB - Shaking and smothering in response to infant crying are life-threatening child abuse. Parental childhood abuse history is known to be one of the most robust risk factors for abusing their offspring. In addition to childhood abuse history, other adverse childhood exposures (ACEs) need to be considered due to co occurrence. However, few studies have investigated the impact of ACEs on caregivers shaking and smothering their infant. This study aims to investigate the association of ACEs with shaking and smothering among caregivers of infants in Japan. A questionnaire was administered to caregivers participating in a four month health checkup between September 2013 and August 2014 in Chiba City, Japan, to assess their ACEs (parental death, parental divorce, mentally ill parents, witness of intimate partner violence, physical abuse, neglect, psychological abuse and economic hardship), and shaking and smothering toward their infants (N=4297). Logistic regression analysis was used to examine the cumulative and individual impacts of ACEs on shaking and smothering. Analyses were conducted in 2015. A total of 28.3% reported having experienced at least one ACE during their childhood. We found that only witness of IPV had a significant association with shaking of infant (OR=1.93, 95% CI: 1.03-3.61). The total number of ACEs was not associated with either shaking or smothering. Our findings suggest that shaking and smothering in response to crying can occur regardless of ACEs. Population based strategies that target all caregivers to prevent shaking and smothering of infants are needed. PMID- 27262605 TI - External validation of the STONE score and derivation of the modified STONE score. AB - OBJECTIVE: The STONE score is a clinical prediction rule for the presence of uncomplicated ureter stones with a low probability of acutely important alternative findings. This study performed an external validation of the STONE score, focusing on the Korean population, and a derivation of the modified STONE score for better specificity and sensitivity. METHODS: We retrospectively reviewed medical records of patients complaining of flank pain at a single emergency department from January 2013 to December 2014. Patients were categorized into 3 groups according to their STONE score. The prevalence of ureter stones and other alternative findings were calculated in each group. We derived a modified STONE score based on a multivariable analysis and performed an interval validation. RESULTS: From the 700 patients included in the analysis, 555 patients (79%) had a ureter stone. The area under the receiver operating characteristic curve of the STONE score was 0.92. The sensitivity of the high stone score was 0.56. In the modified STONE score, nausea, vomiting, and racial predictors were substituted by C-reactive protein and previous stone history. The area under the receiver operating characteristic curve and sensitivity of the modified STONE score in the internal validation group significantly increased to 0.94 and 0.80, respectively. CONCLUSION: The STONE score can be used to predict a ureter stone with a low probability of other alternative findings. The modified STONE score might increase the diagnostic performance in suspicious urinary stone cases. KEY POINTS: We performed external validation of the STONE score and derivation of the modified STONE score. This scoring system could help the clinicians with radiation reducing decision making. PMID- 27262607 TI - Plant Perceptions of Extracellular DNA and RNA. PMID- 27262609 TI - Obstructive Sleep Apnoea: Children are not little Adults. AB - During a child's development, several important developmental physiological sleep processes occur, and, occasionally, pathological disorders occur, which results in differences between obstructive sleep apnoea (OSA) in adults and children. There are major differences in sleep and respiratory physiology as well as OSA symptoms and treatment options between children and adults. Many practitioners do not realize these differences, which results in delays in the diagnosis and treatment of OSA in children. The treatment options for OSA in children are markedly different compared with adults, effective in most children. The use of positive airway pressure (PAP) therapy delivered through continuous or bi-level positive airway pressure modes is successful in children and even in infants; however, there are several challenges facing parents and practitioners to achieve good compliance. The early recognition and treatment of paediatric OSA are essential to prevent deleterious consequences. This article discusses the major differences between paediatric and adult OSA and demonstrates why children are not little adults. PMID- 27262608 TI - Development of diabetes-induced acidosis in the rat retina. AB - We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. PMID- 27262610 TI - Nevoid iris melanoma, case report. AB - CASE REPORT: The case is presented of a patient with diagnosis of iris nevus in the left eye in youth with a poor follow-up, who referred a decreased visual acuity in that eye. A hyphaema and a 3*4*3mm nodule with irregular pigmentation was observed. Excision of the tumour and histological analysis confirmed the suspicion of iris melanoma in stage Ia. DISCUSSION: Despite the low grade malignancy of iris melanoma and the low frequency of transformation of iris nevus into melanoma, a follow-up is required for its early diagnosis and treatment. PMID- 27262611 TI - Role of XPD in cellular functions: To TFIIH and beyond. AB - XPD, as part of the TFIIH complex, has classically been linked to the damage verification step of nucleotide excision repair (NER). However, recent data indicate that XPD, due to its iron-sulfur center interacts with the iron sulfur cluster assembly proteins, and may interact with other proteins in the cell to mediate a diverse set of biological functions including cell cycle regulation, mitosis, and mitochondrial function. In this perspective, after first reviewing the function and some of the key disease causing variants that affect XPD's interaction with TFIIH and the CDK-activating kinase complex (CAK), we investigate these intriguing cellular roles of XPD and highlight important unanswered questions that provide a fertile ground for further scientific exploration. PMID- 27262613 TI - High-resolution genomic assays provide insight into the division of labor between TLS and HDR in mammalian replication of damaged DNA. AB - The multitude of DNA lesions that continuously form in DNA cannot all be detected and removed prior to replication. Thus, encounters of the replication fork with DNA damage become inevitable. Such encounters inhibit fork progression, leading to replication fork arrest or to replication re-priming downstream of the damage site. Either of these events will result in the formation of gap-lesion structures, in which a damaged base is located in a single stranded stretch of DNA, that is vulnerable to subsequent nicking. The double strand break that would ensue if ssDNA becomes nicked constitutes escalation of the damage from nucleotide(s)-specific to chromosomal scale. Cells employ two universal DNA damage tolerance (DDT) strategies to resolve these situations, by converting the gap-lesion structures into dsDNA without repairing the damage. The first is translesion DNA synthesis (TLS), in which a specialized low-fidelity DNA polymerase inserts a nucleotide opposite the damaged one. TLS is inherently mutagenic, due to the miscoding nature of most damaged nucleotides. The second strategy is homology-dependent repair (HDR), which relies on the presence of an identical intact sister chromatid. The molecular mechanisms that regulate the division of labor between these pathways are poorly understood. This review focuses on the balance between TLS and HDR in mammalian cells, discussing recent findings that were made possible thanks to newly developed high resolution genomic assays, and highlighting the role of the DNA lesion's properties in DDT pathway choice. PMID- 27262612 TI - Chemical excitation of electrons: A dark path to melanoma. AB - Sunlight's ultraviolet wavelengths induce cyclobutane pyrimidine dimers (CPDs), which then cause mutations that lead to melanoma or to cancers of skin keratinocytes. In pigmented melanocytes, we found that CPDs arise both instantaneously and for hours after UV exposure ends. Remarkably, the CPDs arising in the dark originate by a novel pathway that resembles bioluminescence but does not end in light: First, UV activates the enzymes nitric oxide synthase (NOS) and NADPH oxidase (NOX), which generate the radicals nitric oxide (NO) and superoxide (O2(-)); these combine to form the powerful oxidant peroxynitrite (ONOO(-)). A fragment of the skin pigment melanin is then oxidized, exciting an electron to an energy level so high that it is rarely seen in biology. This process of chemically exciting electrons, termed "chemiexcitation", is used by fireflies to generate light but it had never been seen in mammalian cells. In melanocytes, the energy transfers radiationlessly to DNA, inducing CPDs. Chemiexcitation is a new source of genome instability, and it calls attention to endogenous mechanisms of genome maintenance that prevent electronic excitation or dissipate the energy of excited states. Chemiexcitation may also trigger pathogenesis in internal tissues because the same chemistry should arise wherever superoxide and nitric oxide arise near cells that contain melanin. PMID- 27262614 TI - Reprint of: Equal egocentric bias in school-aged children with and without autism spectrum disorders. AB - Egocentric bias is a core feature of autism. This phenomenon has been studied using the false belief task. However, typically developing children who pass categorical (pass or fail) false belief tasks may still show subtle egocentric bias. We examined 7- to 13-year-old children with autism spectrum disorder (ASD; n=76) or typical development (n=113) using tasks with a continuous response scale: a modified false belief task and a visual hindsight bias task. All children showed robust egocentric bias on both tasks, but no group effects were found. Our large sample size, coupled with our sensitive tasks and resoundingly null group effects, indicate that children with and without ASD possess more similar egocentric tendencies than previously reported. PMID- 27262615 TI - Clinical and neuroimaging findings in children with gray matter heterotopias: A single institution experience of 36 patients. AB - OBJECTIVE: To describe the clinical spectrum and neuroimaging features of childhood gray matter heterotopias in a single tertiary hospital in Taiwan. METHODS: We retrospectively reviewed the medical records and magnetic resonance images (MRI) of 36 patients with gray matter heterotopias, 19 females and 17 males, between July 1999 and June 2014. The MRI morphologic findings of gray matter heterotopias were recorded along with the presence of associated cerebral malformations. The clinical, electrophysiological and associated systemic malformation data were also recorded. RESULTS: A total of 36 patients were included in the study. Their ages ranged from 1 month to 18 years with a mean age of 3 years 6 months. According to the location of gray matter heterotopias, patients were classified into two groups: periventricular (26) and band (10). The phenotypic spectrum in our population differed from that described previously. In the periventricular group, additional cerebral malformations were found in 18/26 (69%) and systemic malformations in 14/26 (54%). In the band group, additional cerebral malformations were found in 5/10 (50%) and systemic malformations in 2/10 (20%). The majority of patients had developmental delay and intellectual deficit. Twenty-two patients suffered from epileptic seizures with 12 developing refractory epilepsy. CONCLUSIONS: In periventricular heterotopias, the most common associated cerebral malformation was ventriculomegaly, followed by agenesis of corpus callosum. Congenital heart disease was the most common additional systemic malformation. However, the most common associated cerebral malformation was pachygyria in band form. The majority of patients had developmental delay, intellectual deficit, especially in band heterotopias. PMID- 27262616 TI - Neurological complications after gamma-knife radiosurgery for hypothalamic hamartoma. AB - BACKGROUND: The Gamma-knife technique is a safe and effective option for the treatment of hypothalamic hamartomas that produce epileptic seizures refractory to medical treatment and/or serious behavioral disorders. After this type of radiosurgery, an adequate symptomatic control is normally achieved, with notable decrease or even disappearance of the seizures. Radiological changes, such as a decrease in the size of the tumor or adjacent edema secondary to non-necrotizing radioinduced inflammatory reaction are unusual consequences. Side effects and neurological complications are also rare events. CASE PRESENTATION: This report describes an unusual case of complete radiological resolution of a hypothalamic hamartoma as well as neurological complications after Gamma-knife surgery (receiving 13 Gy to the 85% isodose line, 1 cm(3) of tumor volume) in a 8-year old boy who suffered from severe refractory seizures. After radiosurgery, the patient experienced a notable improvement in his symptoms, achieving seizure cessation within 3 months. However, 4 months after the procedure he presented drowsiness, fever and decreased level of consciousness due to a direct effect on the hypothalamus with local and regional edema secondary to the radiosurgery that was performed. He was successfully treated with corticosteroids (with a total duration of 11 months), and twelve months after the surgery, complete disappearance of both the nodular lesion and the secondary edema was observed. The patient remains seizure-free in the last 16 months, with remarkable changes in his behavior. CONCLUSIONS: The present case shows that complete radiological resolution of a hypothalamic hamartoma after Gamma-knife technique is unusual but possible, without long-term neurological consequences. Nevertheless, despite its low incidence, if a patient presents neurological symptoms, primarily during the first year after intervention, possible complications of this type of surgery must be taken into account. PMID- 27262617 TI - Comparison of carbon-ion passive and scanning irradiation for pancreatic cancer. AB - PURPOSE: To compare carbon-ion beam dose distribution between passive and scanning radiation therapies for locally advanced pancreatic cancer. MATERIALS AND METHODS: Thirteen pancreatic cancer patients were included in this study. Four types of treatment planning with respiratory gating were calculated for each patient: a four-field box with passive irradiation (Plan 1), scanning irradiation (Plan 2), a three-field (150 degrees , 180 degrees and 210 degrees ) protocol with passive irradiation (Plan 3), and scanning irradiation (Plan 4). The irradiation plans each delivered 55.2Gy (RBE) to the planning target volume (PTV) and were compared with respect to doses to the PTV and organs at risk (OARs). RESULTS: Plan 3 exceeded the dose assessment metrics to the spinal cord. Scanning irradiation plans (Plan 2 and, particularly, Plan 4) offered significantly reduced dosage to the stomach and the duodenum compared with passive irradiation. CONCLUSION: Three-field oblique scanning irradiation for pancreatic cancer has the potential to reduce gastrointestinal exposure and influence of peristalsis on dose distribution. PMID- 27262619 TI - Short-Term Changes in Choroidal Thickness After Aflibercept Therapy for Neovascular Age-Related Macular Degeneration. PMID- 27262618 TI - A panel study of airborne particulate matter composition versus concentration: Potential for inflammatory response and impaired pulmonary function in children. AB - BACKGROUND: The relationship between airborne particulate matter (PM) and pulmonary function in children has not been consistent among studies, potentially owing to differences in the inflammatory response to PM, based on PM types and sources. The objective of this study was to investigate the effect of airborne PM on pulmonary function in schoolchildren and its potential for an inflammatory response. METHODS: Daily morning peak expiratory flow (PEF) was measured in 339 schoolchildren in February 2015. Interleukin (IL)-8 production was assessed in THP1 cells stimulated by airborne PM collected every day during the study period, and these IL-8 concentrations are described as the daily IL-8 levels. A linear mixed model was used to estimate the association between PEF values and the daily levels of suspended PM (SPM), PM diameters smaller than 2.5 MUm (PM2.5), and IL 8. RESULTS: The daily IL-8 levels were significantly associated with those of SPM and PM2.5. A 0.83 MUg/mL increase in IL-8 levels was significantly associated with a -1.07 L/min (95% confidence interval, -2.05 to -0.08) decrease in PEF. A 12.0 MUg/m3 increase in SPM and a 10.0 MUg/m3 increase in PM2.5 were associated with a -1.36 L/min (-2.93 to 0.22) and -1.72 L/min (-3.82 to 0.36) decreases in PEF, respectively. There were no significant relationships between PEF, SPM, and PM2.5. CONCLUSIONS: These findings suggest that the effects of airborne PM on pulmonary function in schoolchildren might depend more on the pro-inflammatory response than the mass concentration of the PM. PMID- 27262620 TI - Computational predictions suggest that structural similarity in viral polymerases may lead to comparable allosteric binding sites. AB - The identification of ligand-binding sites is often the first step in drug targeting and design. To date there are numerous computational tools available to predict ligand binding sites. These tools can guide or mitigate the need for experimental methods to identify binding sites, which often require significant resources and time. Here, we evaluate four ligand-binding site predictor (LBSP) tools for their ability to predict allosteric sites within the Hepatitis C Virus (HCV) polymerase. Our results show that the LISE LBSP is able to identify all three target allosteric sites within the HCV polymerase as well as a known allosteric site in the Coxsackievirus polymerase. LISE was then employed to identify novel binding sites within the polymerases of the Dengue, West Nile, and Foot-and-mouth Disease viruses. Our results suggest that all three viral polymerases have putative sites that share structural or chemical similarities with allosteric pockets of the HCV polymerase. Thus, these binding locations may represent an evolutionarily conserved structural feature of several viral polymerases that could be exploited for the development of small molecule therapeutics. PMID- 27262622 TI - [Cirsoid aneurysm: Angiographic and OCT patterns]. PMID- 27262621 TI - A novel emaravirus is associated with redbud yellow ringspot disease. AB - Yellow ringspot is the only virus-like disease reported in redbud (Cercis spp.) with symptoms including vein clearing, chlorotic ringspots and oak-leaf pattern. A putative new emaravirus was present in all trees displaying typical yellow ringspot symptoms and the name redbud yellow ringspot associated virus is proposed. The virus genome is composed of at least five RNA segments. Two coding regions were studied to determine isolate diversity with results pointing to a homogeneous virus population. Host range was evaluated using graft transmission and by testing species found in close proximity to infected trees. Mite transmission with Aculops cercidis, the predominant species found in redbud trees in the epicenter of the disease, was evaluated but was not found to be a vector of the virus. Based on this study and the accumulated knowledge on emaravirus evolution we propose that speciation is allopatric, with vectors being a major component of the process. PMID- 27262623 TI - Mydriasis revealing vascular and osteodural compression of the oculomotor nerve: An observational study on five cases. AB - PURPOSE: To describe a form of neurovascular compression of the third cranial nerve (CNIII) in idiopathic mydriasis, in which a neurovascular "conflict" exists between the oculomotor nerve, the posterior communicating artery and the clinoid process, using high-resolution magnetic resonance imaging (MRI) with fast imaging employing steady acquisition (FIESTA) sequences. METHODS: An 18-month prospective, observational and monocentric case series report was performed. MRI was performed on 5 consecutive patients with idiopathic, unilateral, persistent and nonreactive mydriasis (pure intrinsic palsy of the CNIII). Patients with diplopia, ptosis or ophthalmoplegia were excluded. Cerebral MRI focused on the CNIII pathway from the mesencephalon to the cavernous sinus entry, particularly on the cisternal segment: image acquisition was performed on a 3 Tesla MRI; the protocol included fast imaging employing steady acquisition (FIESTA) and three dimension time of flight (3D TOF) sequences. RESULTS: All patients presented a neurovascular compression point, involving the CNIII clamped between a tortuous posterior communicating artery (PCoA) and the posterior clinoid process at the entrance of the cavernous sinus. No cases occurred in the root entry zone. There was no compression on the contralateral side. No tumors or aneurysms were found. Thus, the mydriasis was caused by CNIII compression. CONCLUSION: MRI, including FIESTA sequences, revealed a new type of neurovascular conflict between the CNIII, PCoA and posterior clinoid process in patients with incomplete oculomotor palsy. Non-aneurysmal CNIII compression should be considered as a differential diagnosis in the work-up of idiopathic mydriasis. The role of MRI in the work-up of anisocoria should be considered. PMID- 27262624 TI - Toxicology of potassium channel-directed compounds in mosquitoes. AB - Potential targets for new vector control insecticides are nerve and muscle potassium channels. In this study, the activities of known potassium channel blockers (4-aminopyridine, quinidine, and tetraethylammonium) and the insecticide propoxur were compared to three experimental catechols and several other compounds against Anopheles gambiae and Aedes aegypti mosquitoes. Experimental catechol 1 was the most toxic experimental compound in all of the mortality assays conducted, but was at least 100-fold and 39-fold less toxic than propoxur against Ae. aegypti and An. gambiae, respectively. Injection treatment and synergist (piperonyl butoxide) bioassays found that catechol toxicity was not unduly impacted by cuticular transport or oxidative metabolism. Electrophysiological studies showed a decrease in amplitude of evoked muscle contractions, along with an increase in twitch duration at concentrations that increased basal muscle tension (mM). High concentration effects on basal muscle tension were matched by complete depolarization of the muscle membrane potential. Effects on muscle physiology and blockage of Kv2.1 potassium channels in patch clamp experiments were generally consistent with in vivo toxicity, except for 4 aminopyridine, which suggest the involvement of other potassium channel subtypes. Extensive melanization of Anopheles larvae, but not Aedes larvae, occurred from exposure to catechol compounds. Interaction with the phenol oxidase system within insects may be the cause of this melanization, but any contribution to toxicity requires further investigation. PMID- 27262626 TI - Trefoil factor 3 related to gastrointestinal failure in pediatric critical illness. AB - BACKGROUND: To determine the relationship between the serum concentration of trefoil factor 3 (TFF3) and gastrointestinal failure (GIF) in pediatric critical illness in order to provide knowledge for disease management. MATERIALS AND METHODS: We enrolled 137 cases and divided them into three groups, including a control group (group A), critical illness without GIF (group B), and critical illness with GIF (group C). The serum TFF3 concentration was determined by ELISA and compared among the groups. RESULTS: Serum TFF3 concentrations measured before the occurrence of GIF in group C were significantly higher than in groups A and B (P<0.01). Under the conditions of GIF in group C, serum TFF3 concentration was significantly related to the gastrointestinal tract function score (r=-0.712). Cox's proportional hazards model analysis showed that the serum TFF3 concentrations at the time of occurrence of GIF, and 48hours later, could be used as prognostic factors in critically ill pediatric patients with GIF (r=1.443 and 1.872, respectively). CONCLUSION: TFF3 may play an important role in predicting GIF in pediatric critical illness and has a protective function in the mucosal repair process. PMID- 27262625 TI - The effect of ankle taping on functional performance in participants with functional ankle instability. AB - OBJECTIVE: To investigate the effect of rigid ankle tape on functional performance, self-efficacy and perceived stability, confidence and reassurance during functional tasks in participants with functional ankle instability. DESIGN: Clinical measurement, crossover design. METHODS: Participants (n = 25) with functional ankle instability (Cumberland Ankle Instability Score < 25) were recruited from university students and sporting clubs. Participants performed five functional tests with and without the ankle taped. The tests were: figure-8 hopping test, hopping obstacle course, star excursion balance test (SEBT), single leg stance and stair descent test. Secondary outcome measures were self-efficacy and perception measures. RESULTS: Rigid tape significantly decreased the stair descent time by 4% (p = 0.014), but had no effect on performance in the other tests. Self-efficacy increased significantly (p < 0.001). Perceived stability, confidence and reassurance also increased with the ankle taped (p < 0.05) during the stair and two hopping tasks, but not during the SEBT or single-leg stance test. CONCLUSION: Although taping the ankle did not affect performance, except to improve stair descent, it increased self-efficacy and perceived confidence in dynamic tasks. These findings suggest that taping may reduce apprehension without affecting functional performance in those with functional ankle instability and permit continued physical activity or sport participation. PMID- 27262627 TI - [Perception of adolescent medicine among French pediatric residents]. AB - PURPOSE: The perception of adolescent medicine (AM) among future pediatricians in France has scarcely been explored although adolescent health care is an integral part of the pediatrician's job. Moreover, pediatric residents seem to have a lack of enthusiasm for this field. The aim of this study was to assess the beliefs and perceptions of fourth-year French pediatric residents regarding adolescents and AM. METHODOLOGY: We conducted a national electronic survey among French pediatric residents in their last year of residency. An original 51-item, open-ended declarative questionnaire was sent out including questions on demographics, career expectations, AM block rotation experiences, and perceptions and beliefs regarding adolescents and AM. Difficulties and barriers experienced in this field were investigated. Queries about residents' specific AM courses and about their educational needs were also explored. RESULTS: The survey was conducted online between January and March 2015. There were 121 respondents, achieving a 43% response rate. The majority of respondents perceived teens as interesting (75%), vulnerable (83%), and time-consuming (84%). Up to four fifths of respondents (81%) considered AM to be a skill that all pediatricians should acquire. A subgroup analysis showed that the residents who had not experienced an AM block rotation did not seem to be convinced of the need for training in this field (P=0.09). The following issues were reported as major difficulties by residents: providing care for teens reluctant to seek health care (65%), managing violent behavior among adolescents in the emergency ward (98%), and managing adolescents who attempt suicide (80%). Less than half (45%) of the residents reported their residency program had a specific AM course. Among them, 73% attended the lectures and 57% found them useful. One third (32%) of the respondents had experienced a 2 month block rotation in the field of AM during their residency. DISCUSSION: This is the first nationwide study in France in this field. Although the response rate is below 50%, it exceeded our expectations. Our results are in line with previous studies showing that pediatric residents report a high interest in working with adolescents and yet their educational needs in AM are unmet. The limitations of this study include the self-selection bias and implicit limitations carried by the phrasing of the survey questions. CONCLUSIONS: There is a need to devise a better educational approach combining a broader proposal of AM block rotations together with a specific competency framework in adolescent health, since we know it improves the quality of health care delivered to adolescents. Moreover, training pediatricians in AM is a public health priority so as to comply with medical schools' principles of social accountability and address the priority health needs for an efficient, equitable, and sustainable health system. At a time when postgraduate reform is being made, the inclusion of an AM curriculum in the general pediatrician course is necessary. PMID- 27262628 TI - Dynamic susceptibility contrast perfusion imaging in biopsy-proved adult medulloblastoma. AB - PURPOSE: Medulloblastoma (MB) is a high-grade rare brain tumor in adults, with heterogeneous imaging features and variable enhancing patterns. Diffusion and spectroscopy multimodal imaging have already been described in adult MB, yet perfusion has not been explored. This study aimed to evaluate vascularity in adult classic and desmoplastic MB, using perfusion-weighted dynamic susceptibility contrast (DSC) MRI and histopathology. METHODS: Six histologically proved MB patients were classified as classic (n=3) and desmoplastic (n=3). DSC perfusion MRI was performed in three centers and retrospectively evaluated. Postprocessing included automatic arterial input function, motion and contrast leakage correction. Region of interest (ROI) delineation was performed on three perfusion slices to obtain a total of three cerebral blood volume ratios (rCBV) that were averaged to serve as the main rCBV. Permeability was evaluated on K2 maps. RESULTS: Low rCBVs were observed in all cases (mean rCBV=1.19+/-0.39). rCBV values were lower than 2 for classic MB and lower than 1 for desmoplastic MB. All cases showed an increase of permeability on K2 maps. CONCLUSIONS: Our preliminary results suggest that MB exhibits rCBV values close to 1 and increased permeability on DSC perfusion imaging, especially in desmoplastic cases, which could be explained by fibrous matrix. This type of perfusion pattern contrasts with those given by other enhancing subtentorial tumors such as metastasis, high grade gliomas or hemangioblastomas. PMID- 27262629 TI - Nanotechnology and Nanopore Sequencing. AB - DNA sequencing is one of the crucially important tasks in the fields of genetics and cellular biology, which is benefiting from nanotechnology. DNA carries genetic information and sequencing it in a quick way helps researchers in achieving essential goals, including personalized medicine. Solid state nanopores potentially can offer more durability, in sequencing biomolecules, over the proteinbased nanopores. In recent years, various ideas are introduced towards the goal of fast and low cost sequencing. In this review article recent advances presented in journal articles as well as patents in this field, including sequencing methods, membrane materials and their fabrication techniques, drilling methods, and biomolecule translocation speed control ideas are investigated. PMID- 27262630 TI - Re: Jeffrey J. Tosoian, Debasish Sundi, Bruce J. Trock, et al. Pathologic Outcomes in Favorable-risk Prostate Cancer: Comparative Analysis of Men Electing Active Surveillance and Immediate Surgery. Eur Urol 2016;69:576-81. PMID- 27262631 TI - Survival at extreme altitude - The misery and miracle of aircraft stowaways. PMID- 27262632 TI - The potential association between obesity and bipolar disorder: A meta-analysis. AB - BACKGROUND: Several epidemiological studies have found that the prevalence of bipolar disorder (BD) is significantly higher in obese population than non-obese population. However, no meta-analysis has been published to quantitatively summarize the related literature. METHODS: In this study, we conducted a meta analysis to explore the association between obesity and BD by combining 9 cross sectional studies with a total of 12,259 BD cases and 615,490 non-BD controls. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled odds ratio (OR), while the heterogeneity was assessed using I(2) and Q statistic. RESULTS: Our meta-analysis suggests that obesity is associated with increased prevalence of BD by a random-effect model (OR=1.77, 95% CI: 1.40-2.23; Q=44.62, P<0.001, I(2)=82.1%). LIMITATION: Without prospective studies, we cannot determine whether obesity increased the risk of developing BD or vice-versa. CONCLUSION: Obesity is positively associated with BD. PMID- 27262634 TI - Paternal depression during pregnancy and postpartum: An international Delphi study. AB - BACKGROUND: Fathers are at risk for depression during a mother's gestation and postpartum. Assessment, detection, and treatment are hampered by the lack of consensus on this issue. The purpose of this study was to reach expert consensus through the Delphi method on the defining factors of depression in peripartum fathers. METHODS: Purposive sampling resulted in the surveying of 14 international expert panelists. The study used a modified Delphi approach in which experts participated in two rounds of open-ended and scale questionnaires, followed by two rounds of opportunities to adjust their responses and/or comment on evolving data until consensus was achieved. RESULTS: Experts responded to 10 questions on terminology, diagnostics, symptomology, risk/protective factors, biological factors, assessment tools/protocol, cost implications, and key stakeholders. Of these 10 questions presented for discussion, the analysis resulted in 197 coded themes. Consensus was met for 119 of the 197 coded responses (60.41%). LIMITATIONS: Diversity of opinion within this Delphi Study was excluded for the sake of consensus. Regression to the mean may have occurred after continuous surveying and when evolving results were shared with panelists. Critics of Delphi methodologies have pointed to the issue of small expert samples typically used and the subjectivity of "expert." CONCLUSION: Consensus identified diagnostic criteria and symptomology that differentiates the paternal experience of peripartum depression. Experts indicated the importance of a father's social context, biological risk factors, limitations of current assessment tools, key stakeholders, and potential financial costs. Stakeholders on this issue would benefit from translating consensus into assessment and treatment. PMID- 27262633 TI - Socio-economic status influences the relationship between obesity and antenatal depression: Data from a prospective cohort study. AB - BACKGROUND: Obesity has been associated with increased risk of antenatal depression, but little is known about this relationship. This study tested whether socio-economic status (SES) influences the relationship between obesity and antenatal depression. METHODS: Data were taken from the Screening for Pregnancy Endpoints (SCOPE) cohort. BMI was calculated from measured height and weight at 15+/-1 weeks' gestation. Underweight women were excluded. SES was indicated by self-reported household income (dichotomised around the median: low SES <=L45,000; high SES >L45,000). Antenatal depression was defined as scoring >=13 on the Edinburgh Postnatal Depression Scale at both 15+/-1 and 20+/-1 weeks' gestation, to identify persistently elevated symptoms of depression. RESULTS: Five thousand five hundred and twenty two women were included in these analyses and 5.5% had persistently elevated antenatal depression symptoms. There was a significant interaction between SES and BMI on the risk of antenatal depression (p=0.042). Among high SES women, obese women had approximately double the odds of antenatal depression than normal weight controls (AOR 2.11, 95%CI 1.16-3.83, p=0.014, adjusted for confounders). Among low SES women there was no association between obesity and antenatal depression. The interaction effect was robust to alternative indicators of SES in sensitivity analyses. LIMITATIONS: 1) Antenatal depression was assessed with a self-reported screening measure; and 2) potential mediators such as stigma and poor body-image could not be examined. CONCLUSIONS: Obesity was only associated with increased risk of antenatal depression among high SES women in this sample. Healthcare professionals should be aware that antenatal depression is more common among low SES women, regardless of BMI category. PMID- 27262635 TI - Deliberate self-harm among Chinese medical students: A population-based study. AB - BACKGROUND: The phenomenon of deliberate self-harm (DSH) among college students has received increased attention in recent decades. Adopting a psychosocial perspective, this study aims to describe self-reported DSH among Chinese medical college students, assess respective associations between uncertainty stress and social capital with DSH, and explore the mechanism linking these three phenomena. METHODS: A cross-sectional survey employing multi-stage, sampling was conducted. 4446 undergraduate students were recruited from 22 participating Chinese medical universities. Perceived stress from uncertainty and social capital were assessed among the students. The Chi-square test and multiple logistic regression models assessed correlates of DSH. Relationship among social capital, uncertainty stress, and DSH were examined by means of Structural Equation Modeling. RESULTS: The prevalence of DSH in the past 12 months among Chinese students was 9.6%. The most common types of physical DSH reported were scratching, cutting, and pinching. Age (chi(2)=26.63, p<0.01), gender (chi(2)=30.24, p<0.01), major field (chi(2)=28.13, p<0.01), and annual household income (chi(2)=11.10, p<0.05) were statistically associated with DSH. Uncertainty stress is a unique correlate of DSH, and shows a stronger association than do three certainty stressors. Social capital is also a strong correlate of DSH, especially cognitive social capital. Moreover, social capital may be indirectly associated with DSH through impacting uncertainty stress. LIMITATIONS: This study was a cross-sectional and thus could not evaluate causal relationships. CONCLUSION: We recommend that a DSH intervention study should target uncertainty stress management and social capital accumulation. This study provides scientific evidence and theoretical foundation for future DSH interventions, with a view to enhancing the mental health of medical college students. PMID- 27262636 TI - Pharmacological and psychosocial treatment of depression in primary care: Low intensity and poor adherence and continuity. AB - BACKGROUND: Primary health care bears the main responsibility for treating depression in most countries. However, few studies have comprehensively investigated provision of pharmacological and psychosocial treatments, their continuity, or patient attitudes and adherence to treatment in primary care. METHODS: In the Vantaa Primary Care Depression Study, 1111 consecutive primary care patients in the City of Vantaa, Finland, were screened for depression with Prime-MD, and 137 were diagnosed with DSM-IV depressive disorders via SCID-I/P and SCID-II interviews. The 100 patients with current major depressive disorder (MDD) or partly remitted MDD at baseline were prospectively followed up to 18 months, and their treatment contacts and the treatments provided were longitudinally followed. RESULTS: The median number of patients' visits to a general practitioner during the follow-up was five; of those due to depression two. Antidepressant treatment was offered to 82% of patients, but only 50% commenced treatment and adhered to it adequately. Psychosocial support was offered to 49%, but only 29% adhered to the highly variable interventions. Attributed reasons for poor adherence varied, including negative attitude, side effects, practical obstacles, or no perceived need. About one-quarter (23%) of patients were referred to specialized care at some time-point. LIMITATIONS: Moderate sample size. Data collected in 2002-2004. CONCLUSIONS: The majority of depressive patients in primary health care had been offered pharmacotherapy, psychotherapeutic support, or both. However, effectiveness of these efforts may have been limited by lack of systematic follow-up and poor adherence to both pharmacotherapy and psychosocial treatment. PMID- 27262637 TI - The effect of psychotherapeutic interventions on positive and negative affect in depression: A systematic review and meta-analysis. AB - BACKGROUND: Depression is a mental disorder characterized by high and dysregulated negative affect in addition to diminished positive affect. To our knowledge, there has been no systematic review of the impact of psychotherapeutic interventions on these affective dimensions. METHODS: Two comprehensive literature searches for all randomized controlled trials of psychotherapy in adults with depression were performed. The first from 1996 to December 31, 2014 and the second from January 1, 2015 to December 31, 2015. The primary outcome was the mean score of positive and negative affect. Depressive symptoms were measured to be included as a predictor in the meta-regression analyses. RESULTS: Ten studies with 793 adults with depression were included. All studies assessed positive and negative affect. Psychotherapeutic interventions resulted in significantly increased positive affect (g=0.41; 95% CI: 0.16-0.66 p=0.001), and significantly decreased negative affect (g=0.32; 95% CI: 0.15-0.78, p=0.001) in depressed adults. Because of the small number and substantial heterogeneity of the existing studies the meta-regression analyses produced conflicting results. As a consequence, we were unable to sufficiently demonstrate whether NA and depressive symptoms are in fact correlated or not. LIMITATIONS: Given the small number and heterogeneity of the included studies, the findings should be considered with caution. CONCLUSIONS: Psychotherapeutic interventions demonstrate low to moderate effects in enhancing positive and reducing negative affect in depressed adults. PMID- 27262638 TI - Exploring the excess mortality due to depressive symptoms in a community-based sample: The role of Alzheimer's Disease. AB - BACKGROUND: Depression has been associated with increased risk of death. However, there is lack of studies exploring such relationship in the context of dementia. Given the high prevalence of both depression and Alzheimer's Disease (AD), investigating their temporal association with mortality is of public health relevance. METHODS: Longitudinal data from the WHICAP study were analyzed (1958 individuals aged >=65 years). Depressive symptoms were assessed with the 10-item Center for Epidemiologic Studies Depression Scale (CES-D). Respondents were identified as having AD if they satisfied the criteria of the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Cox regressions analyses were performed to determine the association between depressive symptoms and risk of all-cause mortality using the overall sample, and by AD status. RESULTS: Depressive symptoms were significantly associated with higher mortality risk after adjusting for all potential covariates in the overall sample (HR=1.22; 95% CI=1.02, 1.46) and in individuals with incident AD (HR=1.88; 95% CI=1.12, 3.18). LIMITATIONS: The CES-D does not measure clinical depression but depressive symptomatology. Since those who were exposed to known risk factors for mortality are likely to die prematurely, our results may have been skewed to the individuals with longer survival. CONCLUSIONS: Strategies focusing on prevention and early treatment of depression in the elderly may have a beneficial effect not only on patient quality of life and disability, but may also increase survival in the context of AD. PMID- 27262640 TI - The association between comorbid anxiety disorders and the risk of stroke among patients with diabetes: An 11-year population-based retrospective cohort study. AB - BACKGROUND: Diabetes and anxiety disorders are independent risk factors for stroke. However, it remains unclear whether the risk of stroke is higher among diabetic patients with comorbid anxiety than without comorbid anxiety. Therefore, the purpose of this study was to investigate the association between comorbid anxiety and the risk of stroke among patients with diabetes. METHODS: This is a retrospective cohort study. We used the National Health Insurance Research Database in Taiwan to identify a diabetes cohort with a new diagnosis of an anxiety disorder but without a history of stroke. The enrollment period was 2001 2006 with up to 11 years of follow-up data. Comorbid anxiety was defined by both a clinical diagnosis of the DSM-IV (ICD-9-CM) and prescriptions for anxiolytic medications. Propensity score matching was performed to balance the selected confounders between the anxiety-exposed group and anxiety non-exposed group. Cox propositional hazard regression models were used to evaluate the association between comorbid anxiety and the risk of stroke. RESULTS: Among patients with diabetes (N=40,846), an estimated 5.8% (N=2374) of patients had comorbid anxiety disorders. Diabetic patients with comorbid anxiety were significantly associated with a higher risk of stroke compared to patients without comorbid anxiety (hazard ratio: 1.33, 95% confidence interval: 1.02-1.72). LIMITATIONS: The severity of anxiety or diabetes could not be measured from the claims data. Residual confounding may still exist. CONCLUSION: A significantly elevated risk of stroke was observed in association with comorbid anxiety among patients with diabetes. Psychiatrists should consider routine screening for anxiety disorders to prevent a stroke event among patients with diabetes. PMID- 27262639 TI - Retrospective age-of-onset and projected lifetime prevalence of psychiatric disorders among U.S. Army National Guard soldiers. AB - BACKGROUND: The study of military-related mental health has been disproportionately focused on current symptomology rather than potentially more informative life course mental health. Indeed, no study has assessed age-of-onset and projected lifetime prevalence of disorders among reservists. METHODS: Age-of onset and projected lifetime DSM-IV anxiety, mood, and substance use disorders were assessed in 671 Ohio Army National Guard soldiers aged 17-60 years. Between 2008 and 2012, face-to-face clinical assessments and surveys were conducted using the Structured Clinical Interview for DSM-IV and Clinician-Administered PTSD Scale. RESULTS: Lifetime prevalence of psychiatric disorders was 61%. Alcohol abuse/dependence (44%) and major depressive disorder (23%) were the most common disorders. The majority (64%) of participants reported disorders antedating enlistment. Median age-of-onset varied with anxiety disorders - particularly phobias and OCD - having the earliest (median=15 years) and mood disorders the latest median age-of-onset (median=21 years). LIMITATIONS: The study was limited by both the retrospective investigation of age-of-onset and the location of our sample. As our sample may not represent the general military population, our findings need to be confirmed in additional samples. CONCLUSIONS: Each psychiatric disorder exhibited a distinct age-of-onset pattern, such that phobias and OCD onset earliest, substance use disorders onset during a short interval from late-adolescence to early-adulthood, and mood disorders onset the latest. Our finding that the majority of participants reported disorders antedating enlistment suggests that an assessment of lifetime psychopathology is essential to understanding the mental health burden of both current and former military personnel. PMID- 27262641 TI - The inference-based approach to obsessive-compulsive disorder: A comprehensive review of its etiological model, treatment efficacy, and model of change. AB - BACKGROUND: The inference-based approach (IBA) postulates that individuals with obsessive-compulsive disorder (OCD) confuse a possibility with reality (inferential confusion) according to specific inductive reasoning devices and act as if this possibility were true. A new treatment modality, the inference-based therapy (IBT), was developed. The aim of this study was to critically review empirical evidence regarding the etiological model, treatment efficacy, and model of change of IBA. METHODS: A search of the literature was conducted using PsycINFO and Medline. RESULTS: Thirty-four articles were included in the review. The review reveals that intrusive thoughts of non-clinical and OCD individuals may occur in different contexts. There is support for a specific inductive reasoning style in OCD. Inferential confusion is associated with OCD symptoms. There is good evidence that IBT is an efficacious treatment for OCD, including two randomized controlled trials showing that IBT was as efficacious as cognitive behavior therapy. There is some but limited evidence that the process of change during treatment is coherent with IBA's assumptions. LIMITATIONS: Key premises were investigated in only a few studies. Some of these studies were conducted in non-clinical samples or did not include an anxious control group. CONCLUSIONS: IBA's etiological model, treatment modality, and model of change make a significant contribution to OCD. PMID- 27262642 TI - Ethnic and racial differences in mental health service utilization for suicidal ideation and behavior in a nationally representative sample of adolescents. AB - BACKGROUND: This study examined racial/ethnic differences in mental health treatment utilization for suicidal ideation and behavior in a nationally representative sample of adolescents. METHOD: Data were drawn from the National Survey on Drug Use and Health. Participants included 4176 depressed adolescents with suicidal ideation and behavior in the previous year. Weighted logistic regressions were estimated to examine whether adolescent racial/ethnic minorities had lower rates of past-year treatment for suicidal ideation and behavior in inpatient or outpatient settings, while adjusting for age, depressive symptom severity, family income, and health insurance status. RESULTS: Among adolescents with any suicidal ideation and behavior, and suicide attempts specifically, non Hispanic blacks and Native Americans were less likely than whites to receive outpatient treatment, and multiracial adolescents were less likely to be admitted to inpatient facilities. Apart from Hispanics, racial/ethnic minorities were generally less likely to receive mental health care for suicidal ideation, particularly within psychiatric outpatient settings. A pattern emerged with racial/ethnic differences in treatment receipt being greatest for adolescents with the least severe suicidal ideation and behavior. LIMITATIONS: The cross sectional data limits our ability to form causal inferences. CONCLUSION: Strikingly low rates of treatment utilization for suicidal ideation and behavior were observed across all racial/ethnic groups. Certain racial/ethnic minorities may be less likely to seek treatment for suicidal ideation and behavior when symptoms are less severe, with this gap in treatment use narrowing as symptom severity increases. Native Americans were among the racial/ethnic groups with lowest treatment utilization, but also among the highest for rates of suicide attempts, highlighting the pressing need for strategies to increase mental health service use in this particularly vulnerable population. PMID- 27262643 TI - Results of National, Cluster-Randomized Trial of Duty-Hour Flexibility in Surgical Training: Reflection in Neurosurgery. PMID- 27262644 TI - Tuberculosis Treatment and Traumatic Brain Injury: Where Is the Link? PMID- 27262645 TI - CT Hounsfield Units as a Predictor for the Worsening of Traumatic Vertebral Compression Fractures. AB - INTRODUCTION: With vertebral compression fractures (VCF), height loss has been associated with kyphotic deformity and intractable pain, 2 indications for potential surgical intervention. Consequently, assessment of factors associated with continual height loss can provide insights regarding management. Computed tomography (CT) Hounsfield units (HU), a measure of radiodensity, have been implicated for the assessment of bone quality. No studies have assessed the relationship between CT HU and traumatic VCF. Consequently, the objective of this study was to evaluate this relationship. METHODS: Patients who sustained a traumatic VCF from a motor vehicle accident from 2006 to 2015 were reviewed retrospectively. Inclusion criteria were single VCF from L1 to L4, appropriate imaging, and appropriate follow-up. Clinical data were extracted (age, gender, history of osteoporosis, body mass index [BMI], and length of follow-up). Initial CT imaging was evaluated for averaged HU at the levels above and below the index level of the VCF. Interval percentage change (Delta%) in anterior compression was evaluated between radiographs obtained during initial presentation and at follow up. RESULTS: Age, BMI, and CT HU significantly correlated with Delta% (P < 0.01), whereas initial height loss, history of osteoporosis, and length of follow-up did not. A multiple linear regression for Delta% that combined age, BMI, and CT HU values elicited a regression model with R(2) 0.648, and adjusted R(2) 0.606; each variable in the model showed P < 0.05. A receiver operating characteristic analysis to predict Delta% < 10% from Delta% >=10% showed an area under the curve 0.983 (P < 0.01), where CT HU at 171.58 showed a combination of sensitivity at 0.923 and specificity at 0.91. CONCLUSIONS: Age, BMI, and CT HU values are independent predictors of worsening VCF. These factors can help determine appropriate clinical follow-up and need for surgical intervention. PMID- 27262646 TI - July 2016 Editor-in-Chief Letter. PMID- 27262647 TI - The Clinical Significance of Lumbosacral Transitional Vertebrae on the Surgical Outcomes of Lumbar Discectomy: A Retrospective Cohort Study of Young Adults. AB - OBJECTIVE: To evaluate whether the presence of lumbosacral transitional vertebrae (LSTV) affects the clinical outcomes of microdiscectomy (MD) in young adults with lumbar disc herniation. METHODS: We retrospectively included 398 patients who were followed-up for at least 2 years after MD for lumbar disc herniation at L4/5 (disc above the LSTV). The patients were divided into 2 groups. Group A was made up of 31 patients in whom LSTV was detected. Group B, in contrast, was made up of 35 patients in whom LSTV was not detected. The LSTV were classified using plain radiographs and three-dimensional computed tomography by Castellvi et al. The primary outcome measure was pain intensity at each follow-up visit assessed with visual analog scale for back and leg. Secondary outcome measures included the Oswestry Disability Index, a 12-item short-form health survey for quality of life, complications, and recurrence rate. RESULTS: After surgery, the visual analog scale scores for the back and leg decreased significantly in both groups. However, the back pain intensity in group A worsened at 12 and 24 months postoperatively. The Oswestry Disability Index scores and 12-item short-form health survey (both mental and physical) worsened at 12 and 24 months postoperatively in group A. Two cases of reherniation (6.5 %) were observed in group A, who required reoperation. CONCLUSIONS: LSTV can limit a patient's clinical improvement after MD with regard to pain intensity and recurrence. Caution must be taken when a patient is scheduled to undergo surgery. PMID- 27262648 TI - Alu Methylation in Peripheral Blood Shows Promise for the Diagnosis and Prognostication of Glioma Patients. PMID- 27262649 TI - Endovascular Stenting versus Carotid Endarterectomy for Treatment of Severe Carotid Stenosis: Recent Results from ACT I and the Updated CREST Studies. PMID- 27262650 TI - De Novo Aneurysm Associated with Superficial Temporal Artery to Middle Cerebral Artery Bypass: Report of Two Cases and Review of Literature. AB - BACKGROUND: De novo aneurysm formation has been reported as a rare complication of superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery. CASE DESCRIPTION: The first patient with intracerebral hemorrhage had a ruptured de novo aneurysm arising from the recipient MCA at 6 years after undergoing STA-MCA bypass for hemispheric hemodynamic insufficiency. In the second case, an enlarging unruptured STA aneurysm was detected by follow-up magnetic resonance angiography at 8 years after the patient underwent STA-MCA bypass for moyamoya disease. Both patients were successfully treated by surgical clipping. CONCLUSIONS: Persistent hemodynamic stress with hypertension in an artificial T-shaped vasculature and traumatic injury during surgical manipulation are the most important causes for de novo aneurysms after STA-MCA bypass. Follow up magnetic resonance and computed tomography angiography examinations, along with appropriate blood pressure control, are recommended for patients who have undergone STA-MCA bypass surgery. PMID- 27262652 TI - Surgeon's and Patient's Radiation Exposure Through Vertebral Body Cement Augmentation Procedures: A Prospective Multicentric Study of 49 Cases. AB - OBJECTIVE: Vertebral body cement augmentation as a treatment option for osteoporotic or traumatic fractures has become increasingly popular during the past decade. However, these surgical procedures require numerous fluoroscopic examinations, resulting in high radiation exposure for the patient and the surgical team. The aim of this study was to evaluate the level of radiation exposure of the spine surgeon and the patient during these percutaneous procedures. METHODS: Forty-nine patients admitted for single- or 2-level vertebral compression fracture were prospectively included and treated with vertebral body cement augmentation. For each procedure, radiation dose was measured on the surgeon's whole body, lens, and extremities as well as patient irradiation. Each surgeon wore 2 thermoluminescent dosimeters to measure lens and extremities radiation exposure and 1 electronic personal dosimeter. Patient clinical and surgical data, effective dose to patient, and surgeon were analyzed. RESULTS: Mean operative time was 31.5 +/- 11.7 minutes. The average fluoroscopic time was 61.0 +/- 27.1 seconds. The average whole-body radiation dose per procedure was 1.4 +/- 2.1 MUSv. The average equivalent dose to lens and extremities were 44 MUSv and 59 MUSv, respectively. CONCLUSIONS: Values of radiation doses for surgeon and patient were lower than those reported in the previous literature. The recommended annual dose limit is set to 500 mSv for extremities and 150 mSv for lens. According to our results, the exposure dose to the eye exceeds the annual limit after 3500 procedures. However, there is increasing concern among surgeons about radiation exposure, and there is still a need for solutions as preventive measures. PMID- 27262651 TI - Bracing After Surgical Stabilization of Thoracolumbar Fractures: A Systematic Review of Evidence, Indications, and Practices. AB - BACKGROUND: The role of spinal orthotic braces after surgical stabilization is not clearly defined. We systematically reviewed the published literature to determine patterns of practice, indications, and current evidence for the use of orthotic braces after surgical thoracolumbar fracture stabilization. METHODS: A search was performed for publications including descriptions of postoperative management and outcomes after surgical stabilization of thoracolumbar injuries. Differences between wearing versus not wearing a postoperative brace were examined with regard to loss of deformity correction, pain, return to previous work activity, functional improvement, instrumentation failure rate, pseudoarthrosis, and the percentage of reported complications. RESULTS: This search yielded 76 pertinent studies. Postoperative bracing (POB) was adopted in 62 studies for a median wear time of 13.3 weeks. No significant differences in terms of pain, return to work, Frankel score improvement, or instrumentation failure were found between the POB and non-POB groups. Loss of surgical kyphotic reduction was slightly greater in the POB group (4.79 degrees vs. 3.77 degrees ; P < 0.001). The overall complication rate was also higher in the POB group (16.3% vs. 11.9%; P < 0.01). The pseudoarthrosis rate was lower in the braced group (2.4% vs. 6.0%; P < 0.001). CONCLUSIONS: Most surgeons use braces for 3 months after surgical thoracolumbar fracture stabilization. Given the lack of clinical or biomechanical evidence for this, and the additional costs and potential discomfort to patients, further investigation is warranted to determine when and if POB for surgically stabilized thoracolumbar fractures is indicated. Controlled studies should include a careful analysis of pseudoarthrosis and complication rates. PMID- 27262653 TI - Spontaneous Spinal Epidural Hematoma: A Surgical Case Series of Ten Patients. AB - BACKGROUND: Spontaneous spinal epidural hematoma (SS-EDH) is a rare neurosurgical emergency. Little is known about predictive factors of outcome in patients with SS-EDH. Here, we present a case series of patients operated on for an SS-EDH. METHODS: We reviewed all cases of patients operated on for an SS-EDH between January 2009 and February 2016 in a large academic neurosurgical center. We recorded preadmission functional status, bleeding characteristics, and postsurgery outcome. Good outcome was defined, according to the Nurick score, as at least being able to walk in a way that did not prevent employment. Mean follow up time was 19 months (standard deviation, 25 months). RESULTS: Ten patients, with a mean age of 70 years (standard deviation, 10), with SS-EDH were included. The location of SS-EDH was binomially distributed, with the highest frequencies in the upper thoracic region (Th3-5) and middle to low cervical region (C4-6). Five patients had a poor outcome. Of these, 3 remained chair bound or bedridden. No statistically significant association could be found between preoperative characteristics and outcome, but patients with poor preoperative motor function, thoracic hematoma, and more than 4 involved segments had a high rate of poor neurologic outcome. We could not establish any association between time delay from symptom onset to surgery and outcome. CONCLUSIONS: In our series, half of the patients with SS-EDH recovered well after surgery. Although no statistically significant association could be established, hematoma location, size, and preoperative motor function seem to be some of the most important predictive factors of postoperative recovery. PMID- 27262654 TI - Gamma Knife Radiosurgery in Sphenopetroclival Meningiomas: Preliminary Experience at the Iran Gamma Knife Center. AB - OBJECTIVE: The aims of this study were to characterize the epidemiologic, histologic, and radiologic aspects of sphenopetroclival meningiomas (SpPCMs) and to evaluate the outcome of Gamma Knife radiosurgery (GKRS) either as an adjunct to microsurgery or as a primary SpPCM treatment modality. METHODS: In this retrospective study, medical records of patients with SpPCM who underwent GKRS at the Iran Gamma Knife Center between April 2003 and March 2012 were analyzed. RESULTS: We assessed 122 patients with SpPCMs, including 101 women and 21 men, aged 24-94 years. The mean tumor volume was 12.24 +/- 9.30 mL. Patients received 22.32 +/- 3.29 Gy and 13.18 +/- 1.02 Gy maximal and average marginal dose of GKRS, respectively. The most common complaint was visual impairment, followed by facial sensory impairment and headache. The most frequently involved cranial nerves were III, IV, and VI in 72.1% of patients, followed by II in 52.9%, and V in 35.5%. After radiosurgery, headaches improved in 90.0%, diplopia in 75.0%, and ptosis in 63.0% of patients. On magnetic resonance imaging, tumor size was reduced, unchanged, or increased in 77, 44, and 1 patient, respectively. Progression-free survival at the 5-year follow-up was 56.6%. Younger age (hazard ratio = 0.972, P = 0.011) and lower tumor volume (hazard ratio = 0.959, P = 0.009) were the main prognostic factors for progression-free survival. CONCLUSION: GKRS can be an effective alternative treatment for controlling the progression of SpPCM tumors, producing appropriate clinical outcomes and few complications. PMID- 27262655 TI - How Best to Manage the Spinal Epidural Abscess? A Current Systematic Review. AB - BACKGROUND: A spinal epidural abscess is a medical emergency. Despite urgent surgical intervention and adjuvant antibiotic therapy, neurologic prognosis remains variable and guarded. The optimal approach to managing this condition is debated with substantial variability in clinical practice, dependent on patient demographic and pretreatment neurologic status as well as radiologic appearance. METHODS: A systematic search in MEDLINE and similar databases was conducted for literature published from 1990 to 2015 using the search term "spinal epidural abscess", limiting the search results to human studies published in the English language. Case series that consisted of fewer than 10 patients were excluded. The evidence strength was graded according to the Grades of Recommendation Assessment, Development, and Evaluation criteria. RESULTS: The search yielded 1843 patients from 34 retrospective case series. Ten studies compared surgical and medical management, with no significant difference in patients with good outcome (odds ratio, 0.65; P = 0.11) or neurologic improvement (odds ratio, 1.11; P = 0.69). However, failure rates after initial medical management requiring surgical intervention ranged from 10% to 50%. Three of 4 studies evaluating timing of surgery reported large effect sizes for neurologic outcome if early surgery was performed (P < 0.01). Other prognostic factors from a neurologic perspective included admission neurologic status, patient age, and diabetes mellitus. CONCLUSIONS: Surgery with adjuvant antibiotics remains the optimal treatment for the neurologically symptomatic patient with spinal epidural abscess. If antibiotic therapy alone is considered for the neurologically intact patient, we recommend interdisciplinary medical and surgical consultations with an in-depth dialogue on the potential for failure in isolated medical management and the recommendation for close neurologic monitoring. PMID- 27262656 TI - Element decoupling of 7T dipole body arrays by EBG metasurface structures: Experimental verification. AB - Metasurfaces are artificial electromagnetic boundaries or interfaces usually implemented as two-dimensional periodic structures with subwavelength periodicity and engineered properties of constituent unit cells. The electromagnetic bandgap (EBG) effect in metasurfaces prevents all surface modes from propagating in a certain frequency band. While metasurfaces provide a number of important applications in microwave antennas and antenna arrays, their features are also highly suitable for MRI applications. In this work we perform a proof-of principle experiment to study finite structures based on mushroom-type EBG metasurfaces and employ them for suppression of inter-element coupling in dipole transceive array coils for body imaging at 7T. We firstly show experimentally that employment of mushroom structures leads to reduction of coupling between adjacent closely-spaced dipole antenna elements of a 7T transceive body array, which reduces scattering losses in neighboring channels. The studied setup consists of two active fractionated dipole antennas previously designed by the authors for body imaging at 7T. These are placed on top of a body-mimicking phantom and equipped with the manufactured finite-size periodic structure tuned to have EBG properties at the Larmor frequency of 298MHz. To improve the detection range of the B1+ field distribution of the top elements, four additional elements were positioned along the bottom side of the phantom. Bench measurements of a scattering matrix showed that coupling between the two top elements can be considerably reduced depending on the distance to the EBG structure. On the other hand, the measurements performed on a 7T MRI machine indicated redistribution of the B1+ field due to interaction between the dipoles with the structure. When the structure is located just over two closely spaced dipoles, one can reach a very high isolation improvement of -14dB accompanied by a strong field redistribution. In contrast, when put at a certain height over the antennas the structure provides a moderate isolation improvement together with a slight increase of B1+ level. This study provides a tool for the decoupling of dipole antennas in ultrahigh field transceive arrays, possibly resulting in denser element placement and/or larger subject-element spacing. PMID- 27262657 TI - Parameterized signal calibration for NMR cryoporometry experiment without external standard. AB - In cryoporometric experiments non-linear effects associated with the sample and the probehead bring unwanted contributions to the total signal along with the change of temperature. The elimination of these influences often occurs with the help of an intermediate measurement of a separate liquid sample. In this paper we suggest an alternative approach under certain assumptions, solely based on data from the target experiment. In order to obtain calibration parameters the method uses all of these raw data points. Its reliability is therefore enhanced as compared to other methods based on lesser number of data points. Presented approach is automatically valid for desired temperature range. The need for intermediate measurement is removed and parameters for such a calibration are naturally adapted to the individual sample-probehead combination. PMID- 27262658 TI - Determination of sunset yellow in soft drinks based on fluorescence quenching of carbon dots. AB - Fluorescent carbon dots was prepared by heating N-(2-hydroxyethyl)ethylene diaminetriacetic acid in air. The carbon dots were not only highly soluble in water but also uniform in size, and possessed strong blue fluorescence and excitation wavelength-dependent emission properties with the maximum excitation and emission wavelength at 366nm and 423nm, respectively. Food colorant sunset yellow whose excitation and emission wavelength at 303nm and 430nm could selectively quench the fluorescence of carbon dots, efficient fluorescent resonance energy transfer between the carbon dots and sunset yellow is achieved. This was exploited to design a method for the determination of sunset yellow in the concentration range from 0.3 to 8.0MUmolL(-1), with a limit of detection (3sigma/k) of 79.6nmolL(-1). Furthermore the fluorimetric detection method was established and validated for sunset yellow in soft drinks samples with satisfactory results. PMID- 27262659 TI - Enhanced spectrophotometric detection of Hg in water samples by surface plasmon resonance of Au nanoparticles after preconcentration with vortex-assisted liquid liquid microextraction. PMID- 27262660 TI - An easy prepared dual-channel chemosensor for selective and instant detection of fluoride based on double Schiff-base. AB - A colorimetric and fluorescent dual-channel fluoride chemosensor N,N'-bis (4 diethylaminosalicylidene) hydrazine (sensor S) bearing two imine groups has been designed and synthesized. This structurally simple probe displays rapid response and high selectivity for fluoride over other common anions (Cl(-), Br(-), I(-), AcO(-), H2PO4(-), HSO4(-), ClO4(-), CN(-) and SCN(-)) in a highly polar aqueous DMSO solution. Mechanism studies suggested that the sensor firstly combined with F(-) through hydrogen bonds and then experienced the deprotonation process at higher concentrations of F(-) anion to the two Ar-OH groups. The detection limit was 5.78*10(-7)M of F(-), which points to the high detection sensitivity. Test strips based on sensor S were fabricated, which could act as a convenient and efficient F(-) test kit to detect F(-) for "in-the-field" measurement. PMID- 27262661 TI - A facile fluorescent chemosensor based on a water-soluble porphyrin for Mo(6+) in aqueous solution. AB - A novel water-soluble porphyrin (5,10,15,20-tetra(3-ethoxy-4-hydroxy-5-sulfonate) phenylporphyrin, H2TEHPPS) was synthesized. H2TEHPPS exhibited high sensitivity and selectivity towards Mo(6+). The enhanced fluorescence response of H2TEHPPS after titration with Mo(6+) in aqueous solution at pH3.5 was attributed to the formation of an inclusion complex between the porphyrin ring and Mo(6+), which R(2)=0.999 from 10 to 1000MUgL(-1), providing a detection limit of 1.5MUgL(-1). The fluorescence response of H2TEHPPS towards Mo(6+) showed excellent selectivity over other transition metal cations. PMID- 27262662 TI - Exploring the relationship between childhood obesity and proximity to the coast: A rural/urban perspective. AB - Childhood obesity is one of the 21st century's most serious global health challenges. Research suggests that better access to 'greenspace' (e.g. parks) may encourage physical activity and reduce the risk of obesity amongst children. We extend earlier work by considering childhood obesity in relation to proximity to the coast, using data from England's National Child Measurement Programme. Results suggest that although the overall prevalence of childhood obesity is slightly lower at the coast (-0.68% points comparing <1km to >20km, p<0.001), the relationship depends on area type. Specifically, although a coastal proximity gradient (lower obesity rates nearer the coast) was found for rural areas and smaller cities and towns, it was not present among large urban conurbations (interaction p-value<0.001). Coastal environments and access to them are changing in many areas, and research to explore potential impacts on child health is warranted. PMID- 27262663 TI - On the use of juvenile animal studies to support oncology medicine development in children. PMID- 27262664 TI - The effects of maternal smoking on pregnancy outcome and placental histopathology lesions. AB - OBJECTIVE: To study the effects of maternal smoking on pregnancy outcome and placental histopathology findings. MATERIALS & METHODS: Maternal and labor characteristics and pathological reports were compared between term placentas of complicated and uncomplicated pregnancies of: heavy smokers (>10 cigarettes per day, H-smokers), moderate smokers (<10 cigarettes per day, M-smokers) and non smokers (controls, N-smokers). RESULTS: Birth-weights were lower in the H-smokers and M-smokers as compared to the N-smokers (p<0.001), with a higher rate of small for gestational age (SGA): 18.2%, 19.2% and 11.4%, respectively (p=0.01). Deliveries among smokers were characterized by higher rates of abnormal fetal heart rate tracings during labor as compared to non-smokers (p=0.01). Rates of placental maternal and fetal stromal-vascular supply lesions was similar between the groups. CONCLUSIONS: Maternal smoking is associated with higher rates of SGA. Tobacco's potential influence is probably through the disruption of normal placental epigenetic patterns, not expressed in placental histopathology lesions. PMID- 27262665 TI - Clinical and Research Considerations for Patients With Hypertensive Acute Heart Failure: A Consensus Statement from the Society of Academic Emergency Medicine and the Heart Failure Society of America Acute Heart Failure Working Group. AB - Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF. PMID- 27262666 TI - Aqueous two-phase flotation for primary recovery of bacteriocin-like inhibitory substance (BLIS) from Pediococcus acidilactici Kp10. AB - An aqueous two-phase flotation (ATPF) system based on polyethylene glycol (PEG) and sodium citrate (NaNO3C6H5O7.2H2O) was considered for primary recovery of bacteriocin-like inhibitory substance (BLIS) from Pediococcus acidilactici Kp10. The effects of ATPF parameters namely phase composition, tie-line length (TLL), volume ratio between the two phases (VR), amount of crude load (CL), pH, nitrogen gas flow rate (FR) and flotation time (FT) on the performance of recovery were evaluated. BLIS was mainly concentrated into the upper PEG-rich phase in all systems tested so far. The optimum conditions for BLIS purification, which composed of PEG 8000/sodium citrate, were: TLL of 42.6, VR of 0.4, CL of 22% (w/w), pH 7, average FT of 30min and FR of 20mL/min. BLIS was partially purified up to 5.9-fold with a separation efficiency of 99% under this optimal conditions. A maximum yield of BLIS activity of about 70.3% was recovered in the PEG phase. The BLIS from the top phase was successfully recovered with a single band in SDS gel with molecular weight of about 10-15kDa. ATPF was found to be an effective technique for the recovery of BLIS from the fermentation broth of P. acidilactici Kp10. PMID- 27262667 TI - Educational Placement After Pediatric Intracerebral Hemorrhage. AB - BACKGROUND: This study describes educational placement of school-aged children after spontaneous intracerebral hemorrhage and examines whether educational placement is associated with severity of neurological deficits. METHODS: Children with spontaneous intracerebral hemorrhage presenting from 2007 to 2013 were prospectively enrolled at three tertiary children's hospitals. The Pediatric Stroke Outcome Measure and parental interview gathered information about neurological outcome, school attendance, and educational placement. RESULTS: The cohort of 92 enrolled children included 42 school-aged children (6 to 17 years) with intracerebral hemorrhage. Four children died; one was excluded because of preexisting cognitive deficits. Thirty-seven children completed three-month follow-up, and 30 completed 12-month follow-up. At 12 months, 14 children (46.7%) received regular age-appropriate programming, 12 (40%) attended school with in class services, three (10%) were in special education programs, and one child (3.3%) received home-based services because of intracerebral hemorrhage-related deficits. Of 30 children with three- and 12-month follow-up, 14 (46.7%) improved their education status, 13 (43.3%) remained at the same education level, and three (10%) began to receive in-class services. An increasing Pediatric Stroke Outcome Measure score predicted the need for educational modifications at three months (odds ratio, 3.3; 95% confidence interval, 1.4 to 7.9; P = 0.007) and at 12 months (odds ratio, 2.1; 95% confidence interval, 1.1 to 3.9; P = 0.025). CONCLUSIONS: Most children returned to school within a year after intracerebral hemorrhage, and many had a reduction in the intensity of educational support. However, a great need for educational services persisted at 12 months after intracerebral hemorrhage with fewer than half enrolled in regular age-appropriate classes. Worse deficits on the Pediatric Stroke Outcome Measure were associated with remedial educational placement. PMID- 27262668 TI - Meiofauna distribution in a mangrove forest exposed to shrimp farm effluents (New Caledonia). AB - Meiofauna abundance, biomass and individual size were studied in mangrove sediments subjected to shrimp farm effluents in New Caledonia. Two strategies were developed: i) meiofauna examination during the active (AP) and the non active (NAP) periods of the farm in five mangrove stands characteristics of the mangrove zonation along this coastline, ii) meiofauna examination every two months during one year in the stand the closest to the pond (i.e. Avicennia marina). Thirteen taxonomic groups of meiofauna were identified, with nematodes and copepods being the most abundant ones. Meiofauna abundance and biomass increased from the land side to the sea side of the mangrove probably as a result of the increased length of tidal immersion. Abundance of total meiofauna was not significantly different before and after the rearing period. However, the effluent-receiving mangrove presented twice the meiofauna abundance and biomass than the control one. Among rare taxa, mites appeared extremely sensitive to this perturbation. PMID- 27262670 TI - [Seizure after salmon calcitonin administration: A case report]. PMID- 27262669 TI - Identifying the drivers of abundance and size of the invasive ctenophore Mnemiopsis leidyi in Northwestern Mediterranean lagoons. AB - Acknowledged as among the worst invasive marine species, Mnemiopsis leidyi has spread through European Seas since the mid-1980's. Here we report a bimonthly survey conducted in 2010-11 in three lagoons (Bages-Sigean, Thau and Berre) and at two adjacent coastal stations (Sete and SOMLIT-Marseille) along the French Mediterranean coast. M. leidyi was present only in Berre and Bages-Sigean with maximum abundances observed in late summer. M. leidyi adults were present year round in Berre with the largest organisms (~6 cm) observed in April. In Bages Sigean, they occurred in sufficient abundance to be recorded by fishermen between August and November. Multiple linear regressions highlighted that abundance in both lagoons was mainly influenced by direct effects of salinity and chlorophyll a, and temperature to a lesser extent. While M. leidyi has not yet been recorded in Thau, the lagoon is continually monitored to detect the potential establishment of M. leidyi. PMID- 27262671 TI - Amygdala electrical stimulation inducing spatial memory recovery produces an increase of hippocampal bdnf and arc gene expression. AB - Amygdala seems to promote the consolidation of plastic modification in different brain areas and these long-term brain changes require a rapid de novo RNA and protein synthesis. We have previously shown that basolateral amygdala electrical stimulation produces a partial recovery of spatial memory in fimbria-fornix lesioned animals and it is also able to increase the BDNF protein content in the hippocampus. The emerging question is whether these increased BDNF protein content arises from previously synthesized RNA or from de novo RNA expression. Now we address the question if amygdala electrical stimulation 15min after daily water maze training produces a rapid de novo RNA synthesis in the hippocampus, a critical brain area for spatial memory recovery in fimbria-fornix lesioned animals. In addition, we also study RNA arc expression, a gene which is essential for memory and neural plasticity processes. To this purpose, we study amygdala stimulation effects on the expression of plasticity related-early-genes bdnf and arc in the hippocampus of fimbria-fornix lesioned animals trained in a water-maze for 4days. We also checked on the expression of both genes in non-lesioned, untrained animals (acute condition) at 0.5, 1, 2 and 24h after basolateral amygdala electrical stimulation. Our data from trained animals confirm that daily amygdala electrical stimulation 15min after water maze training produces a partial memory recovery and that is coupled to an increase of bdnf and arc genes expression in the hippocampus. Additionally, the acute study shows that a single session of amygdala stimulation induces a transient increase of both genes (peaking at 30min). These results confirm the memory improving effect of amygdala stimulation in fimbria-fornix-lesioned animals and sustain the assumption that the memory improving effect is mediated by newly synthetized BDNF acting on a memory relevant structure like the hippocampus. The increased amount of BDNF within the hippocampus seems to be locally synthetized by mechanisms activated by the amygdala stimulation. PMID- 27262672 TI - Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator. AB - BACKGROUND: Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac derived uPA. METHODS: Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. RESULTS: Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3+/-6.5 and 70.3+/-36, fold change vs UI, n=8, P<0.007). There was significant up-regulation of cardiac mac Arg1 and YM1 with MI in both WT and uPA null mice (n=4-9 per genotype and condition). Treatment with plasmin increased expression of Arg1 and YM1 in cultured cardiac macs. Histologic analysis revealed increased density of activated fibroblasts and M2 macs in SR-uPA hearts post infarction with associated increases in fibrosis. Cardiac macs isolated from human hearts with ischemic heart disease expressed increased levels of the M2 marker CD206 in comparison to blood-derived macs (4.9+/-1.3). CONCLUSIONS: Cardiac macs in mouse and human hearts adopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. PMID- 27262674 TI - Physiological and pathological cardiac hypertrophy. AB - The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID- 27262673 TI - Mitochondrial therapy improves limb perfusion and myopathy following hindlimb ischemia. AB - Critical limb ischemia is a devastating manifestation of peripheral arterial disease with no effective strategies for improving morbidity and mortality outcomes. We tested the hypothesis that cellular mitochondrial function is a key component of limb pathology and that improving mitochondrial function represents a novel paradigm for therapy. BALB/c mice were treated with a therapeutic mitochondrial-targeting peptide (MTP-131) and subjected to limb ischemia (HLI). Compared to vehicle control, MTP-131 rescued limb muscle capillary density and blood flow (64.7+/-11% of contralateral vs. 39.9+/-4%), and improved muscle regeneration. MTP-131 also increased electron transport system flux across all conditions at HLI day-7. In vitro, primary muscle cells exposed to experimental ischemia demonstrated markedly reduced (~75%) cellular respiration, which was rescued by MTP-131 during a recovery period. Compared to muscle cells, endothelial cell (HUVEC) respiration was inherently protected from ischemia (~30% reduction), but was also enhanced by MTP-131. These findings demonstrate an important link between ischemic tissue bioenergetics and limb blood flow and indicate that the mitochondria may be a pharmaceutical target for therapeutic intervention during critical limb ischemia. PMID- 27262675 TI - Cell sheet technology for the regeneration of gastrointestinal tissue using a novel gastric perforation rat model. AB - PURPOSE: Anastomotic leakage is a major postoperative complication. While cell sheet technology has been gaining popularity in the clinical field, the utility of cell sheets for containing contaminated enteral perforation remains unclear. We established a new gastric perforation rat model and evaluated the efficacy of the myoblast cell sheet to prevent leakage. METHODS: To establish a suitable rat model, perforations of various sizes were made in the stomach. We then pasted the sheet onto the perforated stomach in our new model. After the operation, the rats were sacrificed and analyzed macroscopically and histologically. Serum levels of C-related protein and hyaluronic acid in the peritoneal cavity washing lavage were also evaluated. RESULTS: An incision 5 mm in length was found to be the most suitable for evaluation of the cell sheet performance. In the rats where the cell sheet had been pasted onto the perforation site, we noted less adhesion in the abdominal cavity and a significant reduction in the hyaluronic acid levels in the peritoneal cavity washing lavage. CONCLUSIONS: We evaluated the efficacy of cell sheets for preventing leakage of enteral contents in a gastric perforation rat model. Myoblast cell sheets were able to markedly reduce the degree of both intra abdominal adhesion and inflammation. PMID- 27262676 TI - Clinical outcomes of pancreatic ductal adenocarcinoma resection following neoadjuvant chemoradiation therapy vs. chemotherapy. AB - PURPOSE: We compared the clinical outcomes of pancreatic ductal adenocarcinoma (PDAC) resection after neoadjuvant chemoradiation therapy (NACRT) vs. chemotherapy (NAC). METHODS: The study population comprised 81 patients with UICC stage T3/4 PDAC, treated initially by NACRT with S-1 in 40 and by NAC with gemcitabine + S-1 in 41. This was followed by pancreatectomy with routine nerve plexus resection in 35 of the patients who had received NACRT and 32 of those who had received NAC. We compared the survival curves and clinical outcomes of these two groups. RESULTS: The rates of clinical response, surgical resectability, and margin-negative resection were similar. The NACRT group patients had significantly higher rates of Evans stage >=IIB tumors (29 vs. 0 %, respectively, p = 0.010) and negative lymph nodes (49 vs. 16 %, respectively, p = 0.021) than the NAC group patients. There was no difference in disease-free survival between the groups, but the disease-specific survival of the NAC group patients was better than that of the NACRT group patients (p = 0.034). Patients undergoing pancreatectomy with nerve plexus resection following NACRT had significantly higher rates of intractable diarrhea and ascites but consequently received significantly less adjuvant chemotherapy and therapeutic chemotherapy for relapse. CONCLUSION: NACRT followed by pancreatectomy with nerve plexus resection is superior for achieving local control, but postoperative diarrhea and ascites may prohibit continuation of adjuvant chemotherapy or chemotherapy for relapse (UMIN4148). PMID- 27262677 TI - The cryoablation of lung tissue using liquid nitrogen in gel and in the ex vivo pig lung. AB - PURPOSES: To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. METHODS: Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 degrees C saline and inflated using ventilator to simulate in vivo lung conditions. RESULTS: In gel, the 2.4D and 3.4D probes made iceballs of 3.9 +/- 0.1 and 4.8 +/- 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached -32 +/- 8 and -53 +/- 5 degrees C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 +/- 0.1 and 5.5 +/- 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached -49 +/- 5 and -58 +/- 3 degrees C, respectively. CONCLUSION: Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung. PMID- 27262678 TI - Are fluoxetine's effects due to sigma-1 receptor agonism? PMID- 27262679 TI - The unusual pharmacokinetics of meldonium: Implications for doping. PMID- 27262680 TI - Pimavanserin: First Global Approval. AB - Pimavanserin (NuplazidTM) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis. Up to 60 % of patients with Parkinson's disease may develop Parkinson's disease psychosis, which is associated with increased morbidity and mortality and has few treatment options. This article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis. PMID- 27262681 TI - Emerging Roles of Adipose Progenitor Cells in Tissue Development, Homeostasis, Expansion and Thermogenesis. AB - Stem or progenitor cells are an essential component for the development, homeostasis, expansion, and regeneration of many tissues. Within white adipose tissue (WAT) reside vascular-resident adipose progenitor cells (APCs) that can proliferate and differentiate into either white or beige/brite adipocytes, which may control adiposity. Recent studies have begun to show that APCs can be manipulated to control adiposity and counteract 'diabesity'. However, much remains unknown about the identity of APCs and how they may control adiposity in response to homeostatic and external cues. Here, we discuss recent advances in our understanding of adipose progenitors and cover a range of topics, including the stem cell/progenitor lineage, their niche, their developmental and adult roles, and their role in cold-induced beige/brite adipocyte formation. PMID- 27262682 TI - [Implementation of Multiprofessional Teaching Units of Family and Community Care in Catalonia]. PMID- 27262683 TI - CB1 receptor antagonism prevents long-term hyperexcitability after head injury by regulation of dynorphin-KOR system and mGluR5 in rat hippocampus. AB - Both endocannabinoids and dynorphin are feedback messengers in nervous system that act at the presynaptic nerve terminal to inhibit transmitter release. Many studies showed the cannabinoid-opioid cross-modulation in antinociception, hypothermia, sedation and reward. The aim of this study was to assess the influence of early application of cannabinoid type 1 (CB1) receptor antagonism SR141716A after brain injury on dynorphin-kappa opioid receptor (KOR) system and the expression of metabotropic glutamate receptors (mGluRs) in a rat model of fluid percussion injury (FPI). Firstly, seizure latency induced by pentylenetetrazole was significantly prolonged 6 weeks after brain injury in group of SR141716A treatment. Then, PCR and western blot showed that SR141716A inhibited the long-term up-regulation of CB1 receptors in hippocampus. However, SR141716A resulted in long-term potentiation of dynorphin release and did not influence the up-regulation of KOR in hippocampus after brain injury. Furthermore, SR141716A reverse the overexpression of mGluR5 in the late stage of brain injury. We propose that during the induction of epileptogenesis after brain injury, early application of CB1 receptor antagonism could prevent long-term hyperexcitability by up-regulation of dynorphin-KOR system and prevention of mGluR5 induced epileptogenesis in hippocampus. PMID- 27262685 TI - The effect of solvent grade on thin layer chromatographic analysis of writing inks. AB - The effects on the separation of writing ink dyes and the repeatability of the Rf values from using different grades of chemicals used in solvent system I (SSI) and solvent system II (SSII) for thin-layer chromatographic (TLC) ink analysis were studied. Solvent system I consists of a 70:35:30 mixture of ethyl acetate, ethanol, and water. Solvent system II consists of a 50:10:15 mixture of ethanol, water, and n-butanol. Since 1991, the ASTM International Guideline E 1422 has recommended that the purity of solvents should be "reagent grade" and that water quality should be "distilled or equivalent." A total of 25 blue and 25 black inks were selected for analysis. Thirteen of each color ink were ballpoint and the remainder were non-ballpoint. The observations show that there is a solvent grade effect on both the separation and clarity of the ink dyes and the repeatability of their Rf values. These results indicate that the grades and manufacturers of solvents used in solvent systems for thin-layer chromatography must be consistent. This is especially critical for searching TLC plates against those from a large ink library in casework. Overall, the combination of solvents that produced the best results for solvent system I consisted of denatured ethanol, HPLC grade water, and ACS grade ethyl acetate. There was no consensus for the best combination of solvent grades for solvent system II; however, it was shown that different grades did have an effect on the separation of ink components. PMID- 27262684 TI - Water content of latent fingerprints - Dispelling the myth. AB - Changing procedures in the handling of rare and precious documents in museums and elsewhere, based on assumptions about constituents of latent fingerprints, have led the author to an examination of available data. These changes appear to have been triggered by one paper using general biological data regarding eccrine sweat production to infer that deposited fingerprints are mostly water. Searching the fingerprint literature has revealed a number of reference works similarly quoting figures for average water content of deposited fingerprints of 98% or more. Whilst accurate estimation is difficult there is no evidence that the residue on fingers could be anything like 98% water, even if there were no contamination from sebaceous glands. Consideration of published analytical data of real fingerprints, and several theoretical considerations regarding evaporation and replenishment rates, indicates a probable initial average water content of a fingerprint, soon after deposition, of 20% or less. PMID- 27262686 TI - Toxicity evaluation of wastewater collected at different treatment stages from a pharmaceutical industrial park wastewater treatment plant. AB - The toxicity of water-receiving bodies, the effluent and other treatment stages in wastewater treatment plants has recently been of interest to the public due to the lack of a regulated toxicity-based index for wastewater discharge in China. This study aimed to evaluate the conventional pollution parameters and toxicities of wastewaters collected at different treatment stages from a pharmaceutical industrial park wastewater treatment plant through dehydrogenase activity (DHA) and bioluminescent bacteria (Vibrio qinghaiensis) tests. The results of an analysis of conventional parameters indicated that the total suspended solids (TSS), chemical oxygen demand (COD), total nitrogen (TN), ammonia nitrogen (NH3N), and total phosphorus (TP) were largely removed after various treatments. However, the TN, NH3N and COD still exceeded the regulated standards. The tested pharmaceutical park effluents were mainly polluted with organic pollutants and nitrogenous. The toxicity test results indicated that the toxicities could be markedly reduced after treatment, with the toxicities of two out of the six effluent samples at different treatment stages being greater than the influent toxicity. Spearman's rank correlation coefficients indicated a significantly positive correlation between the toxicity values obtained using the DHA and Vibrio qinghaiensis tests. Compared with the DHA measurement, the Vibrio qinghaiensis test was faster and more sensitive. Meanwhile, the toxicity indicators were significantly and positively correlated with the TSS, TN, TP and COD concentrations. These results may aid the understanding of the toxicity of pharmaceutical industrial park wastewaters and toxicity removal using the treatment techniques that are currently utilized in China. PMID- 27262687 TI - Lowering detection limits for 1,2,3-trichloropropane in water using solid phase extraction coupled to purge and trap sample introduction in an isotope dilution GC-MS method. AB - Purge and trap sample introduction (PTI) has been the premier sampling and preconcentration technique for gas chromatographic determination of volatile organic compounds (VOCs) in drinking water for almost 50 years. PTI affords sub parts-per-billion (ppb) detection limits for purgeable VOCs including fixed gases and higher boiling hydrocarbons and halocarbons. In this study the coupling of solid phase extraction (SPE) to PTI was investigated as a means to substantially increase enrichment and lower detection limits for the emerging contaminant, 1,2,3-trichloropropane (TCP). Water samples (500 mL) were dechlorinated, preserved with a biocide, and spiked with the isotope labeled internal standard, d5-TCP. The entire 500 mL sample was extracted with activated carbon or carbon molecular sieve SPE cartridges, and then eluted with dichloromethane -- excess solvent was removed in a nitrogen evaporator and diethylene glycol "keeper" remaining was dispersed in 5 mL of water for PTI GC-MS analysis. The experimental Method Detection Limit (MDL) for TCP was 0.11 ng/L (ppt) and accuracy was 95-103% in sub-ppt determinations. Groundwater samples including impaired California sources and treated water (n = 21) were analyzed with results ranging from below the method reporting limit (0.30 ng/L) to > 250 ng/L. Coupling of SPE with PTI may provide similar reductions in detection limits for other VOCs with appropriate physical-chemical properties. PMID- 27262688 TI - Is pain sensitivity altered in people with Alzheimer's disease? A systematic review and meta-analysis of experimental pain research. AB - BACKGROUND: Clinical studies suggest people with Alzheimer's disease (AD) have altered pain sensitivity. Experimental pain research is equivocal. OBJECTIVE: Conduct a meta-analysis to investigate if people with AD have altered pain sensitivity compared to healthy controls (HCs). METHODS: Three authors searched electronic databases from inception till November 2015 for experimental pain studies in AD vs. HCs. Outcome measures were pain threshold, tolerance, pain ratings, heart rate response to noxious stimuli and the Facial Action Coding System (FACS). Random effect meta-analysis calculating Hedges' g+/-95% confidence intervals (CI) was conducted. RESULTS: Thirteen studies were identified, including 256 people with AD (74.6 (+/-5.6) years, 59% females with a mean mini mental state examination (MMSE) score of 19.2) and 260 HCs. Meta-analysis demonstrated no significant difference in pain threshold (g=0.025, 95% CI -0.315 0.363, p=0.88, n AD=135, n HCs=157), pain tolerance (g=-0.363, 95% CI -2.035 1.309, p=0.67, n AD=41, n HCs=53) or pain intensity ratings (g=0.03, p=0.89, n AD=138, n HCs=135). Heart rate response to pain was less pronounced in AD but not significant (g=-0.746, p=0.11). People with AD (n=90) had significantly higher FACS scores versus HCs (n=109) (g=0.442, p=0.03) indicating increased pain. Meta regression demonstrated that an increasing percentage of AD female participants moderated pain threshold (p=0.02) whilst MMSE scores did not (p=0.19). CONCLUSION: People with AD have a greater sensitivity to pain when validated observer ratings of facial expressions are used. Verbal response to painful stimuli, even under experimental conditions, may mean pain is not identified in people with AD. Clinically useful observer rated pain tools may be the most appropriate way to assess pain in AD. PMID- 27262689 TI - Older adults demonstrate superior vestibular perception for virtual rotations. AB - Adult ageing results in a progressive loss of vestibular hair cell receptors and afferent fibres. Given the robustness of vestibulo-ocular and vestibular-evoked whole-body responses to age-related deterioration, it was proposed that the vestibular system compensates centrally. Here we examine the potential for central compensation in vestibular sensitivity with adult ageing by using a combination of real and virtual rotation-based psychophysical testing at two stimulus frequencies (0.1 & 1Hz). Real rotations activate semi-circular canal hair cell receptors naturally via mechanotransduction, while electrical current used to evoke virtual rotations does not rely on mechanical deformation of hair cell receptors to activate vestibular afferents. This two-pronged approach allows us to determine the independent effects of age-related peripheral afferent receptor loss and potential compensatory mechanisms. Older adults had thresholds for discriminating real rotations that were significantly greater than young adults at 0.1Hz (7.2 vs. 3 degrees /s), but the effect of age was weaker (non significant) at 1Hz (2.4 vs. 1.3 degrees /s). For virtual rotations, older adults had greater thresholds than young adults at 0.1Hz (1.2 vs. 0.5mA), however, older adults outperformed young adults at 1Hz (0.6 vs. 1.1mA). Based on these thresholds, we argue that central vestibular processing gain is enhanced in older adults for 1Hz real and virtual rotations, partially offsetting the negative impact of normal age-related hair cell receptor and primary afferent loss. We propose that the frequency dependence of this compensation reflects the physiological importance of the 1-5Hz range in natural vestibular input. PMID- 27262691 TI - The nature of primary consciousness. A new synthesis. AB - While the philosophical puzzles about "life" that once confounded biology have all been solved by science, much of the "mystery of consciousness" remains unsolved due to multiple "explanatory gaps" between the brain and conscious experience. One reason for this impasse is that diverse brain architectures both within and across species can create consciousness, thus making any single neurobiological feature insufficient to explain it. We propose instead that an array of general biological features that are found in all living things, combined with a suite of special neurobiological features unique to animals with consciousness, evolved to create subjective experience. Combining philosophical, neurobiological and evolutionary approaches to consciousness, we review our theory of neurobiological naturalism that we argue closes the "explanatory gaps" between the brain and subjective experience and naturalizes the "experiential gaps" between subjectivity and third-person observation of the brain. PMID- 27262690 TI - Implicit learning: A way to improve visual search in spatial neglect? AB - Studies have shown that neglect patients are able to use stimulus regularities to orient faster toward the neglected side, without necessarily being aware of that information, or at the very least without being able to verbalize their knowledge. In order to better control for the involvement of explicit processes, the present study sought to test neglect patients' ability to detect more complex associations between stimuli using tasks similar to those used in implicit learning studies. Our results demonstrate that neglect patients had difficulties implicitly learning complex associations, contrary to what we found with controls. The possible influence of attentional and working memory impairments are discussed. PMID- 27262692 TI - Protective effect of metformin against tuberculosis in diabetic patients. PMID- 27262693 TI - Mass gathering medicine (Hajj Pilgrimage in Saudi Arabia): The clinical pattern of pneumonia among pilgrims during Hajj. AB - The planned annual Hajj to the holy shrines in Makkah, Saudi Arabia, is recognized as one of the largest recurring religious mass gatherings globally, and the outbreak of infectious diseases is of major concern. We aim to study the incidence, etiology, risk factors, length of hospital stay, and mortality rate of pneumonia amongst pilgrims admitted to Al-Ansar general hospital, Madinah, Saudi Arabia during the Hajj period of December 2004-November 2013. A retrospective analysis of all patients diagnosed and admitted as pneumonia was done. Patients were assessed according to the CURB-65 scoring system and admitted to the ward or intensive care unit accordingly. Throat and nasopharyngeal swabs, sputum, and blood culture were collected prior to antibiotic treatment. 1059 patients were included in the study (23% of total hospital admissions and 20% of ICU admissions). The mean age of participants was 56.8 years, the Male:Female ratio was 3:1, and the lengths of stay in the ward and intensive care units were 5 and 14.5 days, respectively. The main organisms cultured from sputum were Klebsiella Pneumoniae, Streptococcus Pneumoniae, Haemophilus Influenzae, Staphylococcus Aureus, Pseudomonas aeruginosa, and community-acquired MRSA. The mortality rate in the ward was 2.4%, while the rate in the ICU was 21.45%. The organisms which caused pneumonia were found to be different during Hajj. The usual standard guideline for the treatment of pneumonia was ineffective for the causative organisms. Therefore, specific adjustments in the guidelines are needed. All efforts should be made to determine the infectious agent. Healthcare workers and pilgrims should adhere to preventive measures. PMID- 27262694 TI - Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection. AB - The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally delivered, non-systemically available therapeutics for use with intravenous beta lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN 004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease. PMID- 27262695 TI - Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review. AB - A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of alpha-amino-3-hydroxy-5 methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not understood, and therefore, more studies are warranted to confirm this hypothesis and explore the specific pathways that might implicate 5-HT. PMID- 27262696 TI - Sex differences in femoral deformity determined using three-dimensional assessment for osteoarthritic knees. AB - PURPOSE: To characterize femoral deformities and determine sex differences in varus knee osteoarthritis (OA), femoral morphology and limb alignment were evaluated by using three-dimensional (3D) assessment, comparing healthy, elderly volunteers with osteoarthritic knees. METHODS: A total of 178 lower limbs of 169 subjects with knee osteoarthritis (136 women, 33 men; mean age 74.9 +/- 5.2 years) and 80 lower limbs of 45 healthy, elderly subjects (24 women, 21 men; mean age 65 +/- 4.9 years) were examined. A 3D extremity alignment assessment system was used to examine the subjects under weight-bearing conditions on biplanar long leg radiographs using a 3D-to-2D image registration technique. The evaluation parameters were (1) femoral bowing in the coronal plane, (2) femoral bowing in the sagittal plane, (3) femoral neck anteversion, (4) hip-knee-ankle angle, and (5) femoral torsion. RESULTS: Higher femoral lateral bowing and slightly higher femoral internal torsion in the proximal diaphysis were observed in women with OA compared with healthy subjects. No difference in the higher varus malalignment, no alteration in the femoral anterior bowing, and no difference in the lower femoral neck anteversion were found between men and women when comparing healthy and OA subjects. CONCLUSIONS: The higher femoral lateral bowing and slightly higher femoral internal torsion in the proximal diaphysis in women are possibly a structural adaptation to mechanical use. The clinical significance is that the femoral deformities and the sex differences in knee OA have the potential to improve the understanding of the aetiology of primary varus knee OA. LEVEL OF EVIDENCE: IV. PMID- 27262697 TI - Early Adolescents' Unique Perspectives of Maternal and Paternal Rejection: Examining Their Across-Dyad Generalizability and Relations with Adjustment 1 Year Later. AB - Parental rejection is linked to deep and enduring adjustment problems during adolescence. This study aims to further clarify this relation by demonstrating what has long been posited by parental acceptance/rejection theory but never validated empirically-namely that adolescents' unique or subjective experience of parental rejection independently informs their future adjustment. Among a longitudinal, multi-informant sample of 161 families (early adolescents were 47 % female and 40 % European American) this study utilized a multitrait-multimethod confirmatory factor analysis to isolate for each early adolescent-parent dyad, the adolescent's distinct view of parental rejection (i.e., the adolescent unique perspective) from the portion of his or her view that overlaps with his or her parent's view. The findings indicated that adolescents' unique perspectives of maternal rejection were not differentiated from their unique perspectives of paternal rejection. Also, consistent with parental acceptance-rejection theory, early adolescents' unique perspectives of parental rejection were associated with worse adjustment (internalizing and externalizing) 1 year later. This study further demonstrates the utility and validity of the multitrait-multimethod confirmatory factor analysis approach for identifying and examining adolescent unique perspectives. Both conceptually and analytically, this study also integrates research focused on unique perspectives with a distinct but related line of research focused on discrepancies in perspectives. PMID- 27262698 TI - A Social Domain Approach to Informant Discrepancies in Parental Solicitation and Family Rules. AB - An extensive body of research has explored the effects of parental monitoring on adolescent outcomes, but studies consistently find substantial discrepancies between parent and adolescent reports of different monitoring behaviors. Little research has examined whether parents and adolescents are more or less discrepant when reporting on parents' rules or solicitation for different adolescent problem and health risk behaviors and few studies have explored potential explanatory variables to explicate individual variability in parent-adolescent discrepant reporting. To address this gap in the literature, the current study examined discrepancies in mother-adolescent reports of family rules and solicitation across five distinct adolescent behaviors: personal behaviors and four different risk behaviors (alcohol-related, cyber, over- and under-eating). Participants were 143 mother-adolescent dyads (Adolescent M age = 14.42, SD = 1.73, range = 12-18, 81 % white, 60 % female). Mean-level discrepancies between maternal and adolescent reports significantly differed by category of adolescent behavior and also varied as a function of reported parental monitoring behavior (rules vs. solicitation). Discrepancies in mother-adolescent reports of behavior-specific rules and solicitation were positively associated with discrepancies in mother and adolescent judgments of the harmfulness of the activities. The results demonstrate that discrepancies in mother-adolescent reports of family process differ by category of adolescent behavior and may be undergirded by differences in mother and adolescent informational assumptions about the potential harm involved with different activities. PMID- 27262699 TI - A Successful Implementation Strategy to Support Adoption of Decision Making in Mental Health Services. AB - Individual involvement in treatment decisions with providers, often through the use of decision support aids, improves quality of care. This study investigates an implementation strategy to bring decision support to community mental health centers (CMHC). Fifty-two CMHCs implemented a decision support toolkit supported by a 12-month learning collaborative using the Breakthrough Series model. Participation in learning collaborative activities was high, indicating feasibility of the implementation model. Progress by staff in meeting process aims around utilization of components of the toolkit improved significantly over time (p < .0001). Survey responses by individuals in service corroborate successful implementation. Community-based providers were able to successfully implement decision support in mental health services as evidenced by improved process outcomes and sustained practices over 1 year through the structure of the learning collaborative model. PMID- 27262700 TI - Biology and clinical application of CAR T cells for B cell malignancies. AB - Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors. PMID- 27262701 TI - The EANM practice guidelines for bone scintigraphy. AB - PURPOSE: The radionuclide bone scan is the cornerstone of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign disease, as well as physiological processes. METHODS: The European Association of Nuclear Medicine (EANM) has written and approved these guidelines to promote the use of nuclear medicine procedures of high quality. CONCLUSION: The present guidelines offer assistance to nuclear medicine practitioners in optimizing the diagnostic procedure and interpreting bone scintigraphy. These guidelines describe the protocols that are currently accepted and used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary. PMID- 27262703 TI - A yo-yo in the heart: a rare presentation of primary cardiac sarcoma as a serpiginous mobile left atrioventricular mass. PMID- 27262704 TI - Erratum to: Unique carbohydrate binding platforms employed by the glucan phosphatases. PMID- 27262702 TI - Amyloid- and FDG-PET imaging in amyotrophic lateral sclerosis. AB - PURPOSE: We aimed to study brain metabolism and presence of beta-amyloid deposits using positron emission tomography (PET) in patients with amyotrophic lateral sclerosis (ALS). METHODS: This prospective cross-sectional study included 18 patients with definite or probable ALS according to the revised El Escorial diagnostic criteria, and 24 healthy controls. Patients underwent neurological and neuropsychological assessments, PET with (18)F-fluorodeoxyglucose (FDG), and amyloid-PET with (18)F-florbetaben. RESULTS: Patients with ALS showed hypometabolism in the frontal area and hypermetabolism in the cerebellum compared to healthy controls. Four patients (22 %) displayed cognitive impairment and decreased metabolism in the frontal area extending bilaterally to the parietal regions, and increased metabolism in the posterior area of the cerebellum. In patients with no cognitive impairment, metabolism was lower in the left superior frontal gyrus and higher in the anterior and posterior lobes of the cerebellum. In the individual analysis, six patients (35 %) displayed more anterior involvement with hypometabolism affecting the superior frontal, medial, and inferior gyri; six patients (35 %) exhibited a more posterior pattern with hypometabolism in the precentral and postcentral gyri and in the superior and inferior parietal lobules; two patients (11 %) showed a mixed pattern; and three patients (17 %) showed no alterations in brain metabolism. Three (16 %) showed increased (18)F-florbetaben uptake compared to controls. CONCLUSIONS: We have identified two main patterns of brain metabolism with an association to cognitive status. Only a subgroup of patients showed an increased uptake of the amyloid tracer. Our results suggest that ALS is heterogeneous from a clinical, metabolic, and molecular standpoint. PMID- 27262705 TI - Impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in stroke patients. AB - Many studies reported that toll-like receptors (TLRs) played an important role in the process of ischemic stroke (IS). However, the impact of TLR5 rs5744174 on stroke risk, gene expression and on inflammatory cytokines, and lipid levels in ischemic stroke patients has not yet been reported and was therefore the subject of this study. In this case-control study, a total of 816 ischemic stroke patients and 816 healthy controls were genotyped using Sequenom MassArray technology. The mRNA expression of TLR5 was detected through quantitative real time PCR among 52 ischemic stroke patients. The levels of IL-1b, IL-6, IL-8, and TNFalpha were measured by ELISA among 62 IS patients. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined among 816 IS patients using a Hitachi 7600 Automatic Biochemistry Analyzer. Our result showed TLR5 rs5744174 polymorphism was not associated with stroke risk, TLR5 mRNA expression and inflammatory cytokines of IS patients (P > 0.050), but was significantly associated with HDL-C (recessive model: beta = - 0.14, 95 % CI: -0.24 to -0.03, P = 0.009). TLR5 rs5744174 polymorphism may have no impact on the stroke risk, gene expression and inflammatory cytokines, but may influence the HDL-C serum level of IS patients in Chinese Han population. PMID- 27262706 TI - Effect of Topical Platelet-Rich Plasma on Burn Healing After Partial-Thickness Burn Injury. AB - BACKGROUND To investigate the effects of platelet-rich plasma on tissue maturation and burn healing in an experimental partial-thickness burn injury model. MATERIAL AND METHODS Thirty Wistar albino rats were divided into 3 groups of 10 rats each. Group 1 (platelet-rich plasma group) was exposed to burn injury and topical platelet-rich plasma was applied. Group 2 (control group) was exposed to burn injury only. Group 3 (blood donor group) was used as blood donors for platelet-rich plasma. The rats were killed on the seventh day after burn injury. Tissue hydroxyproline levels were measured and histopathologic changes were examined. RESULTS Hydroxyproline levels were significantly higher in the platelet rich plasma group than in the control group (P=.03). Histopathologically, there was significantly less inflammatory cell infiltration (P=.005) and there were no statistically significant differences between groups in fibroblast development, collagen production, vessel proliferations, or epithelization. CONCLUSIONS Platelet-rich plasma seems to partially improve burn healing in this experimental burn injury model. As an initial conclusion, it appears that platelet-rich plasma can be used in humans, although further studies should be performed with this type of treatment. PMID- 27262707 TI - Genetics of Cutaneous T Cell Lymphoma: From Bench to Bedside. AB - OPINION STATEMENT: Cutaneous T cell lymphomas (CTCLs) are non-Hodgkin lymphomas of skin homing T cells. Although early-stage disease may be limited to the skin, tumor cells in later stage disease can populate the blood, the lymph nodes, and the visceral organs. Unfortunately, there are few molecular biomarkers to guide diagnosis, staging, or treatment of CTCL. Diagnosis of CTCL can be challenging and requires the synthesis of clinical findings, histopathology, and T cell clonality studies; however, none of these tests are entirely sensitive or specific for CTCL. Treatment of CTCL is often empiric and is not typically based on specific molecular alterations, as is common in other cancers. In part, limitations in diagnosis and treatment selection reflect the limited insight into the genetic basis of CTCL. Recent next-generation sequencing has revolutionized our understanding of the mutational landscape in this disease. These analyses have uncovered ultraviolet radiation and recombination activating gene (RAG) endonucleases as important mutagens. Furthermore, these studies have revealed potentially targetable oncogenic mutations in the T cell receptor complex, NF kappaB, and JAK-STAT signaling pathways. Collectively, these somatic mutations drive lymphomagenesis via cancer-promoting changes in proliferation, apoptosis, and T cell effector function. We expect that these genetic findings will launch a new era of precision medicine in CTCL. PMID- 27262708 TI - Management of High-Risk Squamous Cell Carcinoma of the Skin. AB - OPINION STATEMENT: Non-melanoma skin cancer (NMSC) is the most common malignancy in the USA, with cutaneous squamous cell carcinomas (cSCCs) constituting approximately 20 % of all NMSC. While cSCCs typically behave in an indolent fashion and can be cured with local destructive or surgical methods, a small subset metastasizes and induces significant morbidity and mortality. Identifying and aggressively treating these "high-risk" cSCCs (HRcSCCs) is thus paramount. Recent improvements in staging cSCCs appear to offer better risk stratification than earlier staging criteria. Radiologic imaging and sentinel lymph node biopsy may be beneficial in certain cases of HRcSCC, although more studies are needed before these techniques should be uniformly incorporated into management. Surgery with complete margin control, such as that offered by the Mohs micrographic technique, represents the first-line treatment for these tumors. Radiation therapy is likely most beneficial in the adjuvant setting. Chemotherapy is typically best reserved for patients with metastatic or locally advance disease that is not controllable with surgical and/or radiation therapies. Newer targeted treatments, such as EGFR inhibitors and immunotherapies may offer greater efficacy in these settings, although further evaluation is needed. PMID- 27262709 TI - Assessment of Brain Tumor Response: RANO and Its Offspring. AB - OPINION STATEMENT: Treatment options for most nervous system tumors remain limited and patients are often confronted with significant morbidity and reduced life expectancy. However, significant efforts are underway to find more effective therapies for patients with primary and secondary brain tumors. As more and more clinical trials for nervous system tumors are being conducted, it is increasingly important to optimize the conduct of clinical trials in neuro-oncology. One of the key aspects in this regard is the development of objective and standardized criteria that allow for accurate response assessment in clinical trials and prevent the misclassification of responders and non-responders. Such misclassification may lead to premature discontinuation of an actually effective agent, thereby withholding a potentially active treatment from the patient. Conversely, patients may be inappropriately continued on an inactive treatment. Moreover, such misclassification may confound the data obtained in such studies and may lead to false conclusions with regards to the efficacy of the investigated drug. Therefore, reliable response assessment criteria are necessary that not only accurately capture radiographic changes but also account for treatment-related changes and incorporate the assessment of clinical status and quality of life (QoL). The Response Assessment in Neuro-Oncology (RANO) working group is an international collaboration of neuro-oncologists, medical oncologists, radiation oncologists, neurosurgeons, neuroradiologists, and regulatory groups (among others) commissioned to develop objective and tumor specific response criteria for various tumor subtypes. This article reviews the currently available response criteria for high-grade glioma, low-grade glioma, and brain metastases and discusses some of the barriers to accurate assessment of treatment response in neuro-oncology. PMID- 27262710 TI - Merkel Cell Carcinoma Therapeutic Update. AB - OPINION STATEMENT: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations. PMID- 27262712 TI - Functional limitations in children and adolescents suffering from chronic pain: validation and psychometric properties of the German Functional Disability Inventory (FDI-G). AB - Our objective was to translate the Functional Disability Inventory (FDI) into German, to evaluate its validity and to assess functional limitation in a large cohort of children and adolescents with juvenile fibromyalgia syndrome (jFMS). We administered several questions (e.g., sociodemographics, school-related issues) and questionnaires to 329 patients and one parent. The questionnaires included, among others, a German version of the FDI, the CHAQ (parent report), KIDSCREEN, tender point score (TPS), Depression Inventory for Children and Adolescents (DIKJ) and others. Patients were asked about the severity of pain today (NRS = numerical rating scale) and other symptoms. Internal consistency was evaluated with Cronbach's alpha. Construct validity of the FDI was evaluated by correlating the FDI with the questionnaires as well as with the pain and other variables, e.g., days missed school. An exploratory factor analysis (EFA) was also performed. Mean age was 13.9 years (SD +/-2.48). Means were for pain today 5.37 (+/-2.39) and for the TPS 39.71 (+/-21.56). Internal consistency was alpha = .90. Low-to-moderate correlations were obtained between the FDI and the CHAQ (rho = .51**), KIDSCREEN (e.g., physical well-being rho = -.62**; peers and social support rho = -.28**) as well as the pain variables (NRS rho = .24**; TPS rho = .38**). Psychological variables were also correlated with the FDI (e.g., DIJK rho = .28**). An EFA suggested a two-factor solution. The FDI is a valid instrument for measuring functional limitations in German children and adolescents with jFMS. PMID- 27262711 TI - Targeting the Tumor Environment in Squamous Cell Carcinoma of the Head and Neck. AB - OPINION STATEMENT: The survival rate for patients with advanced stages of squamous cell carcinoma of the head and neck (SCCHN) remains poor despite multimodal treatment options. Cetuximab, an anti-EGFR inhibitor, is the only FDA approved targeted agent for this disease. Recent findings have implicated modifications of the microenvironment and, consequently, phenotypical modifications of the cancer cell, in treatment resistance mechanisms. For many years, cancer research has focused mainly on targetable sites on or inside the cancer cell. Nowadays, in preclinical and clinical studies, a greater emphasis is being placed on drugs that target the tumor microenvironment. Potential targets relate to tumor vascularization, immunology, extracellular matrix components, or cancer-associated fibroblasts. The combination of these new agents with standard treatment options is of particular interest to overcome resistance mechanisms and/or to increase treatment efficacy. Whereas antiangiogenic agents show poor clinical activity, immunotherapy seems to be a more promising tool with an objective response rate (ORR) of 20 % in patients with recurrent and/or metastatic squamous cell carcinoma (R/M SCC). Other targets, located inside the extracellular matrix or on cancer associated fibroblasts, are under preclinical investigation. These new agents all need to be tested in clinical trials alone, or in combination with standard treatment modalities, based on preclinical data. To increase our knowledge of the complex network between the cancer cell and its environment, preclinical studies should consider co-culture models, and clinical studies should incorporate a translational research objective. PMID- 27262713 TI - Prevalence and predictors of unsupervised walking and physical activity in a community population of women with fibromyalgia. AB - Physical exercise is recognized as a component of the evidence-based guidelines for treatment of fibromyalgia. Walking is a low-moderate intensity exercise easily adaptable to a fibromyalgia patient's situation. The present study aims to estimate the prevalence of unsupervised walking for exercise in women with fibromyalgia, to describe their level of physical activity and to identify their predictors among socio-demographic, symptom perception and medical advice to walk. A cross-sectional survey with 920 women (all members of fibromyalgia associations) completed the International Physical Activity Questionnaire-Short Form and self-reported scales to assess symptom perception, walking, medical advice to walk and physical comorbidity. The prevalence of reported walking regularly as physical exercise was 30.8 % and it was predicted by medical advice (odds ratio, OR 1.876), age (OR 1.021) and fatigue intensity (OR 0.912). The prevalence of physical activity was 16 % for high-intensity activity, 40 % for moderate activity and 44 % for low activity. Predictors of low versus moderate and high physical activity were pain intensity (OR 1.171) and fatigue impact perception (OR 1.076). Evidence shows a low percentage of women with fibromyalgia walking regularly for physical exercise. Most reported low or moderate physical activity. The results indicate the importance of doctors' advice in promoting walking. Symptom perception and socio-demographic characteristics were weak predictors. Further work is required to examine other determinants of these low levels. PMID- 27262714 TI - Cross-cultural adaptation and validation of the reliability of the Thai version of the Hip disability and Osteoarthritis Outcome Score (HOOS). AB - HOOS was developed as an extension of the Western Ontario and McMaster Universities' Osteoarthritis Index questionnaire for measuring symptoms and functional limitations related to the hip(s) of patients with osteoarthritis. To determine the validity and reliability of the Thai version of the Hip disability and Osteoarthritis Outcome Score (HOOS) vis-a-vis hip osteoarthritis, the original HOOS was translated into a Thai version of HOOS, according to international recommendations. Patients with hip osteoarthritis (n = 57; 25 males) were asked to complete the Thai version of HOOS twice: once then again after a 3-week interval. The test-retest reliability was analyzed using the intraclass correlation coefficient (ICC). Internal consistencies were analyzed using Cronbach's alpha, while the construct validity was tested by comparing the Thai HOOS with the Thai modified SF-36 and calculating the Spearman's rank correlation coefficients. The Thai HOOS produced good reliability (i.e., the ICC was greater than 0.9 in all five subscales). All of the Cronbach's alpha showed that the Thai HOOS had high internal consistency (Cronbach's alpha greater than 0.8), especially for the pain and ADL subscales (0.89 and 0.90, respectively). The Spearman's rank correlation for all five subscales of the Thai HOOS had moderate correlation with the Bodily Pain subscale of the Thai SF-36. The pain subscale of the Thai HOOS had a high correlation with the Vitality and Social Function subscales of the Thai SF-36 (r = 0.55 and 0.54)-with which the symptom subscale had a moderate correlation. The Thai version of HOOS had excellent internal consistency, excellent test-retest reliability, and good construct validity. It can be used as a reliable tool for assessing quality of life for patients with hip osteoarthritis in Thailand. PMID- 27262715 TI - Improvement of radio frequency (RF) heating-assisted alkaline pretreatment on four categories of lignocellulosic biomass. AB - Pretreatment plays an important role in making the cellulose accessible for enzyme hydrolysis and subsequent conversion because it destroys more or less resistance and recalcitrance of biomass. Radio frequency (RF)-assisted dielectric heating was utilized in the alkaline pretreatment on agricultural residues (corn stover), herbaceous crops (switchgrass), hardwood (sweetgum) and softwood (loblolly pine). Pretreatment was performed at 90 degrees C with either RF or traditional water bath (WB) heating for 1 h after overnight soaking in NaOH solution (0.2 g NaOH/g Biomass). Pretreated materials were characterized by chemical compositional analysis, enzyme hydrolysis, scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The glucan yields of RF heated four categories of hydrolysates were 89.6, 72.6, 21.7, and 9.9 %. Interestingly, RF heating raised glucan yield on switchgrass and sweetgum but not on corn stover or loblolly pine. The SEM images and FTIR spectra agreed with results of composition analysis and hydrolysis. GC-MS detected some compounds only from RF-heated switchgrass. These compounds were found by other researchers only in high-temperature (150-600 degrees C) and high-pressure pyrolysis processes. PMID- 27262716 TI - 3-Chloro-1,2-propanediol biodegradation by Ca-alginate immobilized Pseudomonas putida DSM 437 cells applying different processes: mass transfer effects. AB - 3-Chloro-1,2-propanediol (3-CPD) biodegradation by Ca-alginate immobilized Pseudomonas putida cells was performed in batch system, continuous stirred tank reactor (CSTR), and packed-bed reactor (PBR). Batch system exhibited higher biodegradation rates and 3-CPD uptakes compared to CSTR and PBR. The two continuous systems (CSTR and PBR) when compared at 200 mg/L 3-CPD in the inlet exhibited the same removal of 3-CPD at steady state. External mass-transfer limitations are found negligible at all systems examined, since the observable modulus for external mass transfer Omega ? 1 and the Biot number Bi > 1. Intra particle diffusion resistance had a significant effect on 3-CPD biodegradation in all systems studied, but to a different extent. Thiele modulus was in the range of 2.5 in batch system, but it was increased at 11 when increasing cell loading in the beads, thus lowering significantly the respective effectiveness factor. Comparing the systems at the same cell loading in the beads PBR was less affected by internal diffusional limitations compared to CSTR and batch system, and, as a result, exhibited the highest overall effectiveness factor. PMID- 27262717 TI - Kinetic modeling of Moorella thermoacetica growth on single and dual-substrate systems. AB - Acetic acid is an important chemical raw material that can be produced directly from sugars in lignocellulosic biomass. Development of kinetic models that capture the bioconversion dynamics of multiple sugar systems will be critical to optimization and process control in future lignocellulosic biorefinery processes. In this work, a kinetic model was developed for the single- and dual-substrate conversion of xylose and glucose to acetic acid using the acetogen Moorella thermoacetica. Batch fermentations were performed experimentally at 20 g L(-1) total sugar concentration using synthetic glucose, xylose, and a mixture of glucose and xylose at a 1:1 ratio. The product yield, calculated as total product formed divided by total sugars consumed, was 79.2, 69.9, and 69.7 % for conversion of glucose, xylose, and a mixture of glucose and xylose (1:1 ratio), respectively. During dual-substrate fermentation, M. thermoacetica demonstrated diauxic growth where xylose (the preferred substrate) was almost entirely consumed before consumption of glucose began. Kinetic parameters were similar for the single-substrate fermentations, and a strong linear correlation was determined between the maximum specific growth rate MU max and substrate inhibition constant, K s . Parameters estimated for the dual-substrate system demonstrated changes in the specific growth rate of both xylose and glucose consumption. In particular, the maximum growth rate related to glucose tripled compared to the single-substrate system. Kinetic growth is affected when multiple substrates are present in a fermentation system, and models should be developed to reflect these features. PMID- 27262719 TI - Influent wastewater microbiota and temperature influence anaerobic membrane bioreactor microbial community. AB - Sustainable municipal wastewater recovery scenarios highlight benefits of anaerobic membrane bioreactors (AnMBRs). However, influences of continuous seeding by influent wastewater and temperature on attached-growth AnMBRs are not well understood. In this study, four bench-scale AnMBR operated at 10 and 25 degrees C were fed synthetic (SPE) and then real (PE) primary effluent municipal wastewater. Illumina sequencing revealed different bacterial communities in each AnMBR in response to temperature and bioreactor configuration, whereas differences were not observed in archaeal communities. Activity assays revealed hydrogenotrophic methanogenesis was the dominant methanogenic pathway at 10 degrees C. The significant relative abundance of Methanosaeta at 10 degrees C concomitant with low acetoclastic methanogenic activity may indicate possible Methanosaeta-Geobacter direct interspecies electron transfer. When AnMBR feed was changed to PE, continual seeding with wastewater microbiota caused AnMBR microbial communities to shift, becoming more similar to PE microbiota. Therefore, influent wastewater microbiota, temperature and reactor configuration influenced the AnMBR microbial community. PMID- 27262718 TI - Maleic acid treatment of biologically detoxified corn stover liquor. AB - Elimination of microbial and enzyme inhibitors from pretreated lignocellulose is critical for effective cellulose conversion and yeast fermentation of liquid hot water (LHW) pretreated corn stover. In this study, xylan oligomers were hydrolyzed using either maleic acid or hemicellulases, and other soluble inhibitors were eliminated by biological detoxification. Corn stover at 20% (w/v) solids was LHW pretreated LHW (severity factor: 4.3). The 20% solids (w/v) pretreated corn stover derived liquor was recovered and biologically detoxified using the fungus Coniochaeta ligniaria NRRL30616. After maleic acid treatment, and using 5 filter paper units of cellulase/g glucan (8.3mg protein/g glucan), 73% higher cellulose conversion from corn stover was obtained for biodetoxified samples compared to undetoxified samples. This corresponded to 87% cellulose to glucose conversion. Ethanol production by yeast of pretreated corn stover solids hydrolysate was 1.4 times higher than undetoxified samples, with a reduction of 3h in the fermentation lag phase. PMID- 27262720 TI - Effect of light intensity on the degree of ammonia toxicity on PSII activity of Arthrospira platensis and Chlorella vulgaris. AB - Herein the effect of increasing light intensity on the degree of ammonia toxicity and its impact on the photosynthetic performance of Arthrospira and Chlorella was investigated using Chl fluorescence as a technique to characterize their photosystem II (PSII) activity. The results revealed that the increase of light intensity amplifies the ammonia toxicity on PSII. Chl fluorescence transients shown that at a given free ammonia (FA) concentration (100mg-N/L), the photochemistry potential decreased by increasing light intensity. The inhibition of the PSII was not reversible either by re-incubating the cells under dark or under decreased FA concentration. Moreover, the decrease of photochemical and non photochemical quenching (NPQ) of fluorescence suggest that ammonia toxicity decreases the open available PSII centers, as well the inability of PSII to transfer the generated electrons beyond QA. The collapse of NPQ suggests that ammonia toxicity inhibits the photoprotection mechanism(s) and hence renders PSII more sensitive to photoinhibition. PMID- 27262721 TI - Integrated biorefinery concept for grass silage using a combination of adapted pulping methods for advanced saccharification and extraction of lignin. AB - An integrated refining and pulping process for ensiled biomass from permanent grassland was established on laboratory scale. The liquid phase, containing the majority of water-soluble components, including 24% of the initial dry matter (DM), was first separated by mechanical pressing. The fiber fraction was subjected to high solid load saccharification (25% DM) to enhance the lignin content in the feed for subsequent organosolvation. The saccharification enzymes were pre-selected applying experimental design approaches. Cellulose convertibility was improved by a secondary pressing step during liquefaction. Combined saccharification and organosolvation showed high degree of saccharide solubilization with recovery of 98% of the glucan and 73% of the xylan from the fiber fraction in the hydrolysates, and enabled the recovery of 41% of the grass silage lignin. The effects of the treatment were confirmed by XRD and SEM tracking of cellulose crystallinity and fiber morphology throughout the pulping procedure. PMID- 27262722 TI - Enhanced methane production via repeated batch bioaugmentation pattern of enriched microbial consortia. AB - Using batch and repeated batch cultivations, this study investigated the effects of bioaugmentation with enriched microbial consortia (named as EMC) on methane production from effluents of hydrogen-producing stage of potato slurry, as well as on the indigenous bacterial community. The results demonstrated that the improved methane production and shift of the indigenous bacterial community structure were dependent on the EMC/sludge ratio and bioaugmentation patterns. The methane yield and production rate in repeated batch bioaugmentation pattern of EMC were, respectively, average 15% and 10% higher than in one-time bioaugmentation pattern of EMC. DNA-sequencing approach showed that the enhanced methane production in the repeated batch bioaugmentation pattern of EMC mainly resulted from the enriched iron-reducing bacteria and the persistence of the introduced Syntrophomonas, which led to a rapid degradation of individual VFAs to methane. The findings contributed to understanding the correlation between the bioaugmentation of microbial consortia, community shift, and methane production. PMID- 27262723 TI - Corrigendum to "Phenolic acid protects of renal damage induced by ochratoxin A in a 28-days-oral treatment in rats" [Environ. Toxicol. Pharmacol. 43 (2016) 105 111]. PMID- 27262724 TI - N-terminal region of human ameloblastin synthetic peptide promotes bone formation. AB - The aim of this study was to examine the effect of 16 amino acids of the N terminal region of human ameloblastin (16N-AMBN) synthetic peptide, on the proliferation and differentiation of MC3T3-E1 cells and bone regeneration. While 16N-AMBN did not affect the proliferation, it induced mRNA expression of type I collagen, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin. 16N AMBN also stimulated ALP activity and promoted mineralized nodule formation. On the other hand, these activities were inhibited by anti-16N-AMBN antibody. Treatment of rat calvarial bone defects with 16N-AMBN resulted in almost complete healing compared to that of the control treatments. These findings suggest that 16N-AMBN may be applicable for regeneration therapy of bone defects. PMID- 27262725 TI - Non-Invasive Brain Stimulation Improves Paretic Limb Force Production: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Non-invasive brain stimulation (NIBS) facilitates motor improvements post stroke. Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are representative NIBS techniques frequently used in stroke motor rehabilitation. Our primary question is: Do these two techniques improve force production capability in paretic limbs? OBJECTIVE: The current systematic review and meta-analysis investigated the effects of tDCS and rTMS on paretic limb force production in stroke survivors. METHODS: Our comprehensive search identified 23 studies that reported changes in force production following tDCS or rTMS interventions. Each used random assignment and a sham control group. The 23 qualified studies in our meta-analysis generated 29 comparisons: 14 tDCS and 15 rTMS comparisons. RESULTS: Random effects models indicated improvements in paretic limb force after tDCS and rTMS rehabilitation. We found positive effects on force production in the two sets of stimulation protocols: (a) increasing cortical activity in the ipsilesional hemisphere and (b) decreasing cortical activity in the contralesional hemisphere. Moreover, across acute, subacute, and chronic phases, tDCS and rTMS improved force production. CONCLUSION: Cumulative meta-analytic results revealed that tDCS and rTMS rehabilitation protocols successfully improved paretic limb force production capabilities. PMID- 27262726 TI - Re: A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model. PMID- 27262727 TI - Delivering elsewhere between the first and second deliveries is a risk marker for obstetric complications in the second delivery. AB - PURPOSE: We speculate that parturients who deliver elsewhere between the first and second deliveries compose a unique clinical group, characterized by higher rates of cesarean section (CS) both in the first and second deliveries, compared with parturients who deliver both deliveries at the same hospital. METHODS: A retrospective study conducted at Shaare Zedek Medical Center in a tertiary university-affiliated hospital. The cohort included all women in the second delivery, aged <=24 years with a singleton pregnancy who delivered their second child in our medical center during 2010-2012. Parturients who delivered both the first and second children in our medical center ("stayers") were compared with parturients who delivered their first child in a different hospital ("switchers"). Groups were compared in regard to history of CS in the first delivery and obstetric complications in the second delivery, including CS, instrumental vaginal delivery (IVD), preterm delivery (PTD), and postpartum hemorrhage (PPH). Logistic regressions were constructed to study if delivering elsewhere between the first and second deliveries was a risk for adverse pregnancy outcome, followed by multivariate analysis controlling for confounders. RESULTS: In all, 4166 parturients were included: "stayers" = 3163 and "switchers" = 1003. History of CS in the first delivery was approximately twice as prevalent in "switchers" (12 versus 6.3 %, p < 0.000). "Switchers" experienced higher rates of CS: OR = 1.8 (95 % CI 1.2-2.3); IVD: OR = 1.3 (95 % CI 0.8-2.1); and PTD (<37w): OR = 1.4 (95 % CI 1.0-1.9). CONCLUSIONS: Parturients who deliver elsewhere between the first and second childbirth are at increased risk for CS and PTD in the second delivery; hence, the decision to deliver elsewhere after the first delivery should be considered as a risk marker for obstetric complication. PMID- 27262728 TI - Ocriplasmin - variable efficacy? PMID- 27262729 TI - Psychological impact of anti-VEGF treatments for wet macular degeneration-a review. AB - PURPOSE: To review the current literature on the psychological impact of anti VEGF treatments for wet age-related macular degeneration (wAMD), in terms of patients' experiences of receiving these treatments, and the impact of these treatments for patients' mental health and quality of life. METHODS: We critically analyzed current literature evaluating psychological impact of anti VEGF treatments for wAMD. Primary searches of PubMed, Science Direct, and Web of Science were conducted in July and August of 2015. We reviewed all papers on the topic published until August 5, 2015. RESULTS: Our literature search found 14 papers addressing the psychological impact of anti-VEGF treatments for wAMD. Results highlighted potential anxieties and experiences of pain caused by receiving regular intravitreal injections. A positive visual outcome of anti-VEGF therapy is associated with positive vision-related QOL outcomes, although such association seems to be dependent on improvements on visual acuity. In the literature reviewed, patients receiving anti-VEGF treatments showed a prevalence rate of depression between 20 and 26 %. CONCLUSIONS: Although anti-VEGF treatments can cause some anxiety and being experienced as a stressful event, especially in the beginning of the treatment, preliminary findings suggest a potential benefit for long-term vision-related quality of life. Further longitudinal and qualitative research should bring more evidence on the positive and negative effects of these treatments on patients' long-term mental health. PMID- 27262730 TI - Estimated increase in cross-border purchases by Washington residents following liquor privatization and implications for alcohol consumption trends. AB - AIMS: To estimate changes in liquor sales occurring in Washington, USA and bordering states following the privatization of government controlled liquor stores. DESIGN: Trend analyses of data from January 2009 to October 2014 of a natural experiment beginning 1 June 2012, when liquor prices increased and the number of stores selling liquor increased in the state of Washington. Difference in-differences (DID) models and interrupted time-series methods were used. SETTING: Washington and bordering counties in Oregon and Idaho. MEASUREMENTS: Monthly liquor sales in 9-l cases. FINDINGS: DID model estimates of adjusted change in liquor sales as a result of privatization produced a cross-model average increase of 10.1% in Oregon and 8.2% in Idaho (both P < 0.001). Similar results were found using interrupted time-series. This represents a total loss to Washington of 89 865 l of liquor, 0.226% of total Washington sales, for June 2012 to May 2013. Adding these sales to Washington totals for fiscal years 2013 and 2014, we find that per-capita spirits sales were 5.80 l in both 2012 and 2013, declining slightly to 5.76 l in 2014. CONCLUSIONS: The privatization of liquor sales in the state of Washington, USA in 2012 and the price increases associated with this resulted in a significant increase in sales in bordering counties in the states of Oregon and Idaho. However, the amount of alcohol sales and revenue lost by Washington was relatively small. Per-capita liquor sales in Washington appear to have remained flat after privatization. PMID- 27262732 TI - Comment on Ultrasonographic Diagnosis of Intrauterine Fetal Decapitation Secondary to Amniotic Band Sequence: A Case Report. PMID- 27262733 TI - The Clay Shoveler's Fracture: A Case Report and Review of the Literature. AB - BACKGROUND: A clay-shoveler's fracture is a very rarely occurring stress-type avulsion fracture of the lower cervical or upper thoracic spinous processes owing its name to the clay shovelers of past times. Currently, this type of injury is mainly encountered in individuals practicing sports involving rotational movements of the upper spine. CASE REPORT: We present a case of a man sustaining a clay-shoveler's injury during his work in a horse-riding school. Treatment consisted of a period of rest and analgesics, followed by mobilization as was tolerated. We give a brief historical account of clay shoveler's fractures. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clay-shoveler's fractures are frequently overlooked due to their rareness; however, they have specific clinical features that should alert an attending physician to set the correct diagnosis. This report describes a typical case of a clay-shoveler's fracture, relates to the historical entity of clay-shoveler's fractures, and summarizes existing literature on this topic. PMID- 27262734 TI - Neck Pain in a 12-Year-Old Female: An Unusual Diagnosis. AB - BACKGROUND: Neck pain in the pediatric population has a broad differential diagnosis, ranging from benign to imminently life-threatening causes. Trauma and infection represent the most common etiologies of pediatric neck pain in the pediatric emergency department (PED) setting. Malignancy, though a rare cause of pediatric neck pain, is important to consider in patients with acquired torticollis or focal neurologic signs. CASE REPORT: We describe the case of a previously healthy 12-year-old female who presented to the PED with neck pain radiating down her upper extremities. The physical examination revealed diminished strength in her upper extremities compared to her lower extremities. Further evaluation revealed lymphadenopathy in the cervical and mediastinal areas and an epidural tumor in the cervical spinal column. The ultimate diagnosis was Hodgkin lymphoma presenting in an unusual manner with cervical spinal cord compression. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Neck pain is a common chief complaint among pediatric patients in the emergency setting. This case of spinal cord compression caused by malignancy illustrates the necessity of detailed spinal imaging in patients with neck pain and "red flag" signs, including but not limited to an abnormal neurologic examination. PMID- 27262731 TI - DNA Polymerases Divide the Labor of Genome Replication. AB - DNA polymerases synthesize DNA in only one direction, but large genomes require RNA priming and bidirectional replication from internal origins. We review here the physical, chemical, and evolutionary constraints underlying these requirements. We then consider the roles of the major eukaryotic replicases, DNA polymerases alpha, delta, and E, in replicating the nuclear genome. Pol alpha has long been known to extend RNA primers at origins and on Okazaki fragments that give rise to the nascent lagging strand. Taken together, more recent results of mutation and ribonucleotide incorporation mapping, electron microscopy, and immunoprecipitation of nascent DNA now lead to a model wherein Pol E and Pol delta, respectively, synthesize the majority of the nascent leading and lagging strands of undamaged DNA. PMID- 27262735 TI - Red Blood Cell Transfusion in the Emergency Department. AB - BACKGROUND: Transfusion of red blood cells (RBCs) is the primary management of anemia, which affects 90% of critically ill patients. Anemia has been associated with a poor prognosis in various settings, including critical illness. Recent literature has shown a hemoglobin transfusion threshold of 7 g/dL to be safe. This review examines several aspects of transfusion. OBJECTIVE: We sought to provide emergency physicians with an updated review of indications for RBC transfusion in the emergency department. DISCUSSION: The standard hemoglobin transfusion threshold was 10 g/dL. However, the body shows physiologic compensatory adaptations to chronic anemia. Transfusion reactions and infections are rare but can have significant morbidity and mortality. Products stored for <21 days have the lowest risk of reaction and infection. A restrictive threshold of 7 g/dL is recommended in the new American Association of Blood Banks guidelines and multiple meta-analyses and supported in gastrointestinal bleeding, sepsis, critical illness, and trauma. Patients with active ischemia in acute coronary syndrome and neurologic injury require additional study. The physician must consider the patient's hemodynamic status, comorbidities, risks and benefits of transfusion, and clinical setting in determining the need for transfusion. CONCLUSIONS: RBC transfusion is not without risks, including transfusion reaction, infection, and potentially increased mortality. The age of transfusion products likely has no effect on products before 21 days of storage. A hemoglobin level of 7 g/dL is safe in the setting of critical illness, sepsis, gastrointestinal bleeding, and trauma. The clinician must evaluate and transfuse based on the clinical setting and patient hemodynamic status rather than using a specific threshold. PMID- 27262737 TI - Transforming veterans health care through academic-practice partnerships. AB - The Veterans Health Affairs Office of Academic Affiliations (OAA) has invested in the creation of academic-practice partnerships to transform the care of veterans and their families. This article details how a long-standing relationship between the University of Alabama at Birmingham School of Nursing and the Birmingham Veterans Affairs Medical Center grew into such a partnership. The three programs that now exist within the Birmingham Veterans Affairs Nursing Academic Partnership (VANAP) umbrella are described, including an undergraduate VA nurse scholars program that has sustained beyond OAA funding, a VANAP graduate education program for psychiatric mental health nurse practitioners (NPs), and a Mental Health NP Residency. Key features of the programs are noted as are outcomes and lessons learned for building mutual goals and a sustainable academic practice partnership. With the recent passage of the Veterans Choice Program, the importance of educating all nurses about veterans and veterans' health is stressed. PMID- 27262736 TI - Structural equation modelling exploration of the key pathophysiological processes involved in cardiac surgery-related acute kidney injury in infants. AB - BACKGROUND: Uncertainties about the pathophysiological processes resulting in cardiac surgery-related acute kidney injury (AKI) in infants concern the relative impact of the most prominent risk factors, the clinical relevance of changes in glomerular filtration rate vs tubular injury, and the usefulness of available diagnostic tools. Structural equation modelling could allow for the assessment of these complex relationships. METHODS: A structural model was specified using data from a prospective observational cohort of 200 patients <1 year of age undergoing cardiopulmonary bypass surgery. It included four latent variables: AKI, modelled as a construct of perioperative creatinine variation, of oliguria and of urine neutrophil gelatinase-associated lipocalin (uNGAL) concentrations; the cardiopulmonary bypass characteristics; the occurrence of a post-operative low cardiac output syndrome and the post-operative outcome. RESULTS: The model showed a good fit, and all path coefficients were statistically significant. The bypass was the most prominent risk factor, with a path coefficient of 0.820 (95 % CI 0.527-0.979), translating to a 67.2 % explanation for the risk of AKI. A strong relationships was found between AKI and early uNGAL excretion, and between AKI and the post-operative outcome, with path coefficients of 0.611 (95 % CI 0.347 0.777) and 0.741 (95 % CI 0.610-0.988), respectively. The path coefficient between AKI and a >50 % increase in serum creatinine was smaller, with a path coefficient of 0.443 (95 % CI 0.273-0.596), and was intermediate for oliguria, defined as urine output <0.5 ml kg(-1) h(-1), with a path coefficient of 0.495 (95 % CI 0.250-0.864). A path coefficient of -0.229 (95 % CI -0.319 to 0.060) suggested that the risk of AKI during the first year of life did not increase with younger age at surgery. CONCLUSIONS: These findings suggest that cardiac surgery-related AKI in infants is a translation of tubular injury, predominately driven by the cardiopulmonary bypass, and linked to early uNGAL excretion and to post-operative outcome. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01219998 . Registered 11 October 2010. PMID- 27262738 TI - Utilizing MOST frameworks and SMART designs for intervention research. PMID- 27262739 TI - Organizational climate and self-efficacy as predictors of staff strain in caring for dementia residents: A mediation model. AB - PURPOSE OF THE STUDY: To date, no research has investigated how the organizational climate of aged care influences the self-efficacy of staff in caring for residents with dementia, or, how self-efficacy is associated with the strain experienced by staff. This study sought to investigate the extent to which the self-efficacy of aged care staff mediates the association between organizational climate variables (such as autonomy, trusting and supportive workplace relations, and the recognition of competence and ability, and perceptions of workplace pressure) and staff strain. DESIGN AND METHODS: A cross sectional survey design was implemented in which 255 residential aged care staff recruited across aged care facilities in Melbourne, Australia. Staff completed self-report measures of organizational climate, self-efficacy, and strains in caring for residents with dementia. RESULTS: Indirect effects analyses using bootstrapping indicated that self-efficacy of staff mediated the association between the organizational climate variables of autonomy, trust, support, pressure, and staff strain. IMPLICATIONS: The findings of this study emphasize that the aged care sector needs to target organizational climate variables that enhance the self-efficacy of staff, and that this in turn, can help ameliorate the strain experienced by staff caring for residents experiencing dementia. PMID- 27262740 TI - Synthesis and application of poly(ethylene glycol)-co-poly(beta-amino ester) copolymers for small cell lung cancer gene therapy. AB - The design of polymeric nanoparticles for gene therapy requires engineering of polymer structure to overcome multiple barriers, including prolonged colloidal stability during formulation and application. Poly(beta-amino ester)s (PBAEs) have been shown effective as polymeric vectors for intracellular DNA delivery, but limited studies have focused on polymer modifications to enhance the stability of PBAE/DNA polyplexes. We developed block copolymers consisting of PBAE oligomer center units and poly(ethylene glycol) (PEG) end units. We fabricated a library of PEG-PBAE polyplexes by blending PEGylated PBAEs of different PEG molecular weights and non-PEGylated PBAEs of different structures at various mass ratios of cationic polymer to anionic DNA. Non-PEGylated PBAE polyplexes aggregated following a 24h incubation in acidic and physiological buffers, presenting a challenge for therapeutic use. In contrast, among 36 PEG PBAE polyplex formulations evaluated, certain polyplexes maintained a small size under these conditions. These selected polyplexes were further evaluated for transfection in human small cell lung cancer cells (H446) in the presence of serum, and the best formulation transfected ~40% of these hard-to-transfect cells while preventing polymer-mediated cytotoxicity. When PEG-PBAE polyplex delivered Herpes simplex virus thymidine kinase plasmid in combination with the prodrug ganciclovir, the polyplexes killed significantly more H446 cancer cells (35%) compared to healthy human lung fibroblasts (IMR-90) (15%). These findings indicate that PEG-PBAE polyplexes can maintain particle stability without compromising their therapeutic function for intracellular delivery to human small cell lung cancer cells, demonstrate potential cancer specificity, and have potential as safe materials for small cell lung cancer gene therapy. STATEMENT OF SIGNIFICANCE: Many natural and synthetic biomaterials have been investigated as non-viral vectors to deliver nucleic acids for cancer therapy. However, there are multiple hurdles to successful transfection including achieving particle stability, efficient delivery to cancer cells, and low cytotoxicity. In particular, engineering the physicochemical surface properties of a nanoparticle to improve stability is often offset by a decrease in the cellular entry and transfection efficiency. We developed stable polymeric nanoparticles that demonstrate high transfection efficiency by modifying synthetic biodegradable cationic polymers and engineering nanoparticle formulations using a combinatorial approach. The results of this study show the potential of biodegradable surface modified polymeric nanoparticles as clinically translatable, biomaterial-based vehicles for cancer gene therapy. PMID- 27262741 TI - Vascularization of three-dimensional engineered tissues for regenerative medicine applications. AB - Engineering of three-dimensional (3D) tissues is a promising approach for restoring diseased or dysfunctional myocardium with a functional replacement. However, a major bottleneck in this field is the lack of efficient vascularization strategies, because tissue constructs produced in vitro require a constant flow of oxygen and nutrients to maintain viability and functionality. Compared to angiogenic cell therapy and growth factor treatment, bioengineering approaches such as spatial micropatterning, integration of sacrificial materials, tissue decellularization, and 3D bioprinting enable the generation of more precisely controllable neovessel formation. In this review, we summarize the state-of-the-art approaches to develop 3D tissue engineered constructs with vasculature, and demonstrate how some of these techniques have been applied towards regenerative medicine for treatment of heart failure. STATEMENT OF SIGNIFICANCE: Tissue engineering is a promising approach to replace or restore dysfunctional tissues/organs, but a major bottleneck in realizing its potential is the challenge of creating scalable 3D tissues. Since most 3D engineered tissues require a constant supply of nutrients, it is necessary to integrate functional vasculature within the tissues in order to facilitate the transport of nutrients. To address these needs, researchers are employing biomaterial engineering and design strategies to foster vessel formation within 3D tissues. This review highlights the state-of-the-art bioengineering tools and technologies to create vascularized 3D tissues for clinical applications in regenerative medicine, highlighting the application of these technologies to engineer vascularized cardiac patches for treatment of heart failure. PMID- 27262742 TI - An injectable silk sericin hydrogel promotes cardiac functional recovery after ischemic myocardial infarction. AB - Acute myocardial infarction (MI) leads to morbidity and mortality due to cardiac dysfunction. Here we identify sericin, a silk-derived protein, as an injectable therapeutic biomaterial for the minimally invasive MI repair. For the first time, sericin prepared in the form of an injectable hydrogel has been utilized for cardiac tissue engineering and its therapeutical outcomes evaluated in a mouse MI model. The injection of this sericin hydrogel into MI area reduces scar formation and infarct size, increases wall thickness and neovascularization, and inhibits the MI-induced inflammatory responses and apoptosis, thereby leading to a significant functional improvement. The potential therapeutical mechanisms have been further analyzed in vitro. Our results indicate that sericin downregulates pro-inflammatory cytokines (TNF-alpha and IL-18) and chemokine (CCL2) and reduces TNF-alpha expression by suppressing the TLR4-MAPK/NF-kappaB pathways. Moreover, sericin exhibits angiogenic activity by promoting migration and tubular formation of human umbilical vessel endothelial cells (HUVECs). Also, sericin stimulates VEGFa expression via activating ERK phosphorylation. Further, sericin protects endothelial cells and cardiomyocytes from apoptosis by inhibiting the activation of caspase 3. Together, these diverse biochemical activities of sericin protein lead to a significant recovery of cardiac function. This work represents the first study reporting sericin as an effective therapeutic biomaterial for ischemic myocardial repair in vivo. STATEMENT OF SIGNIFICANCE: Intramyocardial biomaterial injection is thought to be a potential therapeutic approach to improve cardiac performance after ischemic myocardial infarction. In this study, we report the successful fabrication and in vivo application of an injectable sericin hydrogel for ischemic heart disease. We for the first time show that the injection of in situ forming crosslinked sericin hydrogel promotes heart functional recovery accompanied with reduced inflammatory responses, attenuated apoptosis and increased microvessel density in the infarcted hearts. Further, we reveal that the improvement in those aspects is ascribed to sericin protein's functional bioactivities that are comprehensively uncovered in this study. Thus, we identify sericin, a natural protein, as a biomaterial suitable for myocardial repair and demonstrate that the in vivo application of this injectable sericin hydrogel can be an effective strategy for treating MI. PMID- 27262743 TI - Frequent use of household cleaning products is associated with rhinitis in Chinese children. AB - BACKGROUND: Despite the popular use of household cleaning products worldwide, there is no published study investigating the health effects of these products on rhinitis in children. OBJECTIVE: We sought to investigate the household use of cleaning products and rhinitis patterns in Chinese children. METHODS: A total of 2299 children were recruited from 21 primary schools with wide geographic coverage in Hong Kong. Self-administered questionnaires were completed by parents/guardians to collect detailed information on respiratory symptoms and household use of 14 types of chemical cleaning products, as well as clean water. Students were categorized into 4 mutually exclusive rhinitis patterns (never, occasional, frequent, and persistent). The total chemical burden (TCB) score was used as the exposure indicator by calculating the total time of exposure to the 14 cleaning products. Multinomial logistic regression was used to assess the relationship between rhinitis patterns and the use of household cleaning products. RESULTS: Every 10-unit increment of TCB score was associated with an increase in the odds of occasional (odds ratio [OR], 1.21; 95% CI, 1.05-1.41), frequent (OR, 1.36; 95% CI, 1.13-1.60), and persistent (OR, 1.21; 95% CI, 1.01 1.56) rhinitis after adjustment for a wide range of potential confounders. Compared with the children within the lowest tertile of TCB scores, the adjusted ORs of occasional, frequent, and persistent rhinitis in children within the highest tertile were 1.29 (95% CI, 1.01-1.65), 1.97 (95% CI, 1.40-2.76), and 1.67 (95% CI, 1.10-2.54), respectively. CONCLUSION: Frequent use of chemical cleaning products at home is associated with an increase in the odds of rhinitis in Chinese primary school children. PMID- 27262744 TI - Synergistic effects of air pollution and psychosocial stressors on adolescent lung function. PMID- 27262746 TI - 5-lipoxygenase pathway is essential for the control of granuloma extension induced by Schistosoma mansoni eggs in lung. AB - According to WHO, it is estimated that approximately 2 billion people are infected with intestinal helminths worldwide and the number of people who are cured of these diseases is relatively low, resulting in a large percentage of chronically infected individuals. Schistosomiasis is one of the most important parasitic diseases present in developing countries configuring it as a serious public health problem, directly related to poverty and social disadvantage. Once the parasite infection is established, Schistosoma mansoni eggs fall into the bloodstream and are trapped in the liver microcirculation where a strong granulomatous response and fibrosis formation occurs. In the experimental model, granulomas develop in the mouse lung after intravenous injection of purified eggs. Here we aim to understand how leukotrienes are involved in the granuloma formation. Leukotrienes are lipid mediators derived from arachidonic acid metabolites via 5-lipoxygenase (5LO) enzyme. They are potent proinflammatory agents and induce recruitment, cell activation, regulation of microbicidal activity of polymorphonuclear and mononuclear cells. In this study, 5LO deficient mice (5LO(-/-)) were inoculated with S. mansoni eggs for evaluation of immunopathological parameters involved in the induction of type 2 granulomas. We showed that in the absence of leukotrienes, the size of granulomas were decreased comparing to the wild type mice and the inflammatory compromised areas had a lower extension. In 5LO(-/-) mice granulomas presented extensive areas of fibrosis, detected by alpha-SMA expression along the lesions, indicating remodeling in attempt to reestablish the normal tissue. Also, comparing to WT mice we detected decrease of IL-4 and IL-13 and increase of TGF-beta in the lung of 5LO(-/-), but these mice failed to produce protective IFN-gamma and IL-12. These results evidenced 5-Lipoxygenase as an important pathway during lung injury due to Schistosoma-eggs injection. PMID- 27262745 TI - Primary Immune Deficiency Treatment Consortium (PIDTC) update. AB - The Primary Immune Deficiency Treatment Consortium (PIDTC) is a collaboration of 41 North American centers studying therapy for rare primary immune deficiency diseases (PIDs), including severe combined immune deficiency (SCID), Wiskott Aldrich syndrome (WAS), and chronic granulomatous disease (CGD). An additional 3 European centers have partnered with the PIDTC to study CGD. Natural history protocols of the PIDTC analyze outcomes of treatment for rare PIDs in multicenter longitudinal retrospective, prospective, and cross-sectional studies. Since 2009, participating centers have enrolled more than 800 subjects on PIDTC protocols for SCID, and enrollment in the studies on WAS and CGD is underway. Four pilot projects have been funded, and 12 junior investigators have received fellowship awards. Important publications of the consortium describe the outcomes of hematopoietic cell transplantation for SCID during 2000-2009, diagnostic criteria for SCID, and the pilot project of newborn screening for SCID in the Navajo Nation. The PIDTC Annual Scientific Workshops provide an opportunity to strengthen collaborations with junior investigators, patient advocacy groups, and international colleagues. Funded by the National Institute of Allergy and Infectious Diseases and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, the PIDTC has recently received renewal for another 5 years. Here we review accomplishments of the group, projects underway, highlights of recent workshops, and challenges for the future. PMID- 27262747 TI - Metal artefact reduction algorithm for correction of bone biopsy needle artefact in paediatric C-arm CT images: a qualitative and quantitative assessment. PMID- 27262748 TI - Cystic fibrosis in Latin America-Improving the awareness. AB - The burden of cystic fibrosis (CF) in Latin America is being increasingly recognized and is significant compared with other regions of the world. In this short communication, we assess the current situation in some Latin American countries and make suggestions for possible directions for future focus. We discuss the work that remains in deciphering how the various genetic, environmental and medical factors interact and influence outcomes in different ethnic groups. We also consider the need for consistency in both research and access to services across Latin America, including CF registries, neonatal screening programs, access to specialized CF healthcare practitioners, transition to adult clinics and treatment regimens. Progress in these areas is likely to build on the advances to date, and improve the lives of patients in Latin America who are affected by this debilitating and life-limiting disorder. PMID- 27262750 TI - Handball Practice Enhances Bone Mass in Specific Sites Among Prepubescent Boys. AB - This investigation's purpose is to focus on the effects of practicing handball for at least 2 yr on bone acquisition among prepubescent boys. One hundred prepubescent boys aged 10.68 +/- 0.85 yr were divided into 2 groups: 50 handball players (HP group) and 50 controls (C group). Bone mineral density (BMD), bone mineral content (BMC), and bone area (BA) were evaluated by using dual-photon X ray absorptiometry on the whole body, lumbar spine (L2-L4), legs, arms, femoral necks, hips and radiuses. Results showed greater values of BMD in both right and left femoral neck and total hip in handball players than in controls. In addition, handball players had higher values of legs and right total hip BMC than controls without any obvious variation of BA measurement in all sites between groups. All results of the paired t-test displayed an obviously marked variation of bone mass parameters between the left and right sides in the trained group without any marked variation among controls. Data showed an increased BMD of the supporting sites between the left and the right leg among handball players. However, "BMC" results exhibited higher values in the right than in the left total hip, and in the right total radius than in the left correspondent site. In addition, differences in the "BA" measurements were observed in the left total hip and in the right arm. Specific bone sites are markedly stimulated by handball training in prepubescent boys. PMID- 27262749 TI - [A case of partial 1p36.1 deletion and partial trisomy 6p diagnosed by karyotype]. AB - : The deletion of chromosomal region 1p36 is one of the most common sub-telomeric microdeletion syndromes and has distinctive dysmorphic features. On the other hand, partial trisomy of the short arm of chromosome 6 is a rare chromosomal abnormality with a variable phenotype. OBJECTIVE: To report a case with both chromosome abnormalities, and to highlight the importance of the karyotype as a diagnostic tool in dysmorphology. CLINICAL CASE: The case of is presented of a two month-old infant with several craniofacial anomalies, neck haemangioma, sacral pit, rhizomelic shortening, small hands and feet, left unilateral cryptorchidism, and hypotonia. The infant also suffered intrauterine growth restriction and is the product of the eighth pregnancy of a 28 years old woman. Due to the unspecific findings in phenotype, a karyotype was requested, which showed a partial deletion of 1p36.1 and a partial trisomy of chromosome 6. CONCLUSION: The development of new techniques in molecular biology has improved diagnostic possibilities in medical genetics. However, the traditional karyotype remains as an important diagnostic tool in patients with multiple congenital anomalies. PMID- 27262751 TI - Nontuberculous mycobacteria in cystic fibrosis patients on the Island of Gran Canaria. A population study. AB - OBJECTIVE: To determine the prevalence of nontuberculous mycobacteria (NTM) colonization and disease in cystic fibrosis (CF) patients. PATIENTS AND METHODS: All the CF patients followed-up from 2002 to 2012 with three acid-fast bacilli (AFB) cultures were included. The American Thoracic Society (ATS) criteria for NTM lung disease were applied. RESULTS: Forty-four of the 53 patients being followed-up were included. The mean time of follow-up was 7.0 years. A total of 18 patients (40.9%) were NTM positive. The NTN mean annual prevalence was 14.1%. The risk of Mycobacterium abscessus complex was higher in the group of 10-14 years-old (p < 0.001). Ten patients (22.7% of the entire cohort) met the ATS microbiological criteria. The mean annual prevalence of NTM disease was 10.4%. Seven patients (four with Mycobacterium simiae and three with M. abscessus complex) with multiple positive cultures, positive AFB smears and clinical worsening were treated. Three patients with M. simiae and none of those with M. abscessus were cured. CONCLUSIONS: Overall NTM prevalence of colonization and disease were high in our CF patients. Patients <15 years old had a higher risk of M. abscessus complex colonization. Multiple positive cultures or positive AFB smears were associated with disease. PMID- 27262752 TI - Do gallstones found before sleeve gastrectomy behave the same as those formed after surgery due to weight loss? AB - BACKGROUND: Gallstone formation is prevalent in the bariatric population and after weight loss. We believe that gallstones found preoperatively behave differently and may not cause significant complications as those developing after weight loss. Thus, prophylactic cholecystectomy before or during sleeve gastrectomy (SG) may not be necessary. METHODS: Patients undergoing SG from January 2011 to May 2012 were evaluated for the presence of gallstones and development of symptoms or need for cholecystectomy postoperatively. RESULTS: Group 1 (n = 18) had gallstones preoperatively. Group 2 (n = 29) developed gallstones after weight loss. Both groups' demographics were similar. Symptomatic gallstones occurred in 1 patient (5.6%) in group 1 and in 9 patients (31.0%) in group 2 (P = .19). Percent excess body mass index loss (%EBL) was 58 +/- 24% vs 70 +/- 22% (P = .11) with a mean follow-up of 8.9 +/- 6.2 and 14.7 +/- 3.9 months for group 1 and group 2, respectively (P = .005). CONCLUSIONS: Asymptomatic gallstones found before SG tend to have less risk of becoming symptomatic than those formed after weight loss. There was no statistical significant difference because of small sample. Prophylactic cholecystectomy, however, may not be warranted in these patients. PMID- 27262753 TI - Outcomes of early ileocolectomy after percutaneous drainage for perforated ileocolic Crohn's disease. AB - BACKGROUND: The optimal treatment for an intra-abdominal abscess/infection secondary to perforating ileocolic Crohn's disease (PCD) is unclear. METHODS: Forty-seven consecutive PCD patients treated via an institutional protocol of ileocolectomy after a 7-day period of percutaneous abscess drainage were retrospectively compared with 160 consecutive patients who underwent an elective ileocolectomy for Crohn's disease (ECD) between 1992 and 2014. Outcomes were compared using univariate analysis and propensity score matching. RESULTS: Univariate analysis demonstrated significant differences in ileostomy rates (PCD: 48.9% vs ECD: 18.8%; P = .001), 30-day readmissions (PCD: 38.3% vs ECD: 18.8%; P = .01), and overall 30-day postoperative complications (PCD: 29.8% vs ECD: 15%; P = .03). After matching, a statistically significant difference was retained in ileostomy rates (P = .02) and 30-day readmissions (P = .01). CONCLUSIONS: Early operative intervention after percutaneous drainage in perforating CD may be associated with a high incidence of diversions and readmissions. PMID- 27262754 TI - Is there value in alvimopan in minimally invasive colorectal surgery? AB - BACKGROUND: Alvimopan's goal is to minimize postoperative ileus and optimize outcomes; however, evidence in laparoscopic surgery is lacking. Our goal was to evaluate the benefit of alvimopan in laparoscopic colorectal surgery with an enhanced recovery pathway (ERP). METHODS: Laparoscopic colorectal cases were stratified into alvimopan and control cohorts, then case-matched for comparability. All followed an identical ERP. The main outcomes were length of stay, complications, readmissions, and costs in the alvimopan and control groups. RESULTS: About 321 patients were analyzed in each cohort. Operative times were comparable (P = .08). Postoperatively, complication rates were similar (P = .29), with no difference in ileus (P = 1.00). The length of stay (3.69 vs 3.49 days; P = .16), readmission (2.8% vs 3.7%; P = .66) and reoperation rates (2.2% vs 1.6%; P = .77) were comparable for alvimopan and controls, respectively. Total costs were similar ($14,932.47 alvimopan vs $14,846.56 controls; P = .90), but the additional costs in the alvimopan group could translate to savings of $27,577 in the cohort. CONCLUSIONS: Alvimopan added no benefit in patient outcomes in laparoscopic colorectal surgery with an ERP. These results could drive a change in current practice. Controlled studies are warranted to define the cost and/or benefit in clinical practice. PMID- 27262755 TI - Is a surgical approach justified for octogenarians with pancreatic carcinoma? Projecting surgical decision making for octogenarian patients. AB - BACKGROUND: In recent years, more elderly patients have undergone surgery for pancreatic cancer, although the safety and efficacy of performing complex pancreatic resections in patients older than 80 years remain controversial. METHODS: Patients with pancreatic cancer who underwent curative surgical treatment were divided into 2 subgroups: the younger group (<80 years) and the octogenarian group (>=80 years). RESULTS: From March 2005 to December 2013, 194 consecutive surgically curable patients with diagnosed pancreatic cancer were studied, among which 34 (17.5%) were of 80 years or older. There were no significant differences in postoperative severe complication rates for younger and octogenarian groups (16% vs 20%, respectively) or perioperative mortality rates (1.3% vs .0%). The incidence of postoperative delirium in the octogenarian group was greater than that in the younger group (23.5% vs 3.8%). CONCLUSIONS: Octogenarian pancreatic cancer patients should not be denied a priori the opportunity for surgery, particularly if the patient represents an ideal candidate and if the co-operation of the family can be obtained. PMID- 27262756 TI - Genetic profiling of hepatocellular carcinoma using next-generation sequencing. AB - Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, both clinically and from a molecular standpoint. The advent of next-generation sequencing technologies has provided new opportunities to extensively analyze molecular defects in HCC samples. This has uncovered major cancer driver genes and associated oncogenic pathways operating in HCC. More sophisticated analyses of sequencing data have linked specific nucleotide patterns to external toxic agents and defined so-called 'mutational signatures' in HCC. Molecular signatures, taking into account intra- and inter-tumor heterogeneity, and their functional validation could provide useful data to predict treatment response to molecular therapies. In this review we will focus on the current knowledge of deep sequencing in HCC and its foreseeable clinical impact. PMID- 27262757 TI - Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions. AB - BACKGROUND & AIMS: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. METHODS: We studied the two populations of KCs using intravital microscopy, morphometric analysis and gene expression profiling. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allowed discrimination between these two KC sub-types. RESULTS: Bone marrow derived "KCs" accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts. Reflecting the differential expression of scavenger receptors, yolk sac-derived KCs were more effective at accumulating acetylated low density lipoprotein, whereas surprisingly, they were poorer than bone marrow-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to lipopolysaccharide challenge, ii) phagocytosis of effete red blood cells and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. CONCLUSIONS: Bone marrow derived KCs differentiate locally to resemble yolk sac-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology. LAY SUMMARY: Liver macrophages play a major role in the control of infections in the liver and in the pathology associated with chronic liver diseases. It was recently shown that liver macrophages can have two different origins, however, the extent to which these populations are functionally distinct remains to be fully addressed. Our study demonstrates that whilst liver macrophages share many features in common, regardless of their origin, some subtle differences in function exist. DATA REPOSITORY: Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954). PMID- 27262758 TI - Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study. AB - BACKGROUND & AIMS: HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy. METHODS: From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hepatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12weeks after the end of treatment. RESULTS: The SVR rate 12weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p<0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs. CONCLUSIONS: Treatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence. LAY SUMMARY: The recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs. PMID- 27262760 TI - Exercise-Dependent Regulation of NK Cells in Cancer Protection. AB - Natural killer (NK) cells are the most responsive immune cells to exercise, displaying an acute mobilization to the circulation during physical exertion. Recently, exercise-dependent mobilization of NK cells was found to play a central role in exercise-mediated protection against cancer. Here, we review the link between exercise and NK cell function, focusing on circulating exercise factors and additional effects, including vascularization, hypoxia, and body temperature in mediating the effects on NK cell functionality. Exercise-dependent mobilization and activation of NK cells provides a mechanistic explanation for the protective effect of exercise on cancer, and we propose that exercise represents a potential strategy as adjuvant therapy in cancer, by improving NK cell recruitment and infiltration in solid tumors. PMID- 27262761 TI - Re: Zhu M, Xie Y, Zhu Y, Chai G, Li Q. A novel noninvasive three-dimensional volumetric analysis for fat graft survival in facial recontouring using the 3L and 3M technique. J Plast Reconstr Aesthet Surg. 2016;69(2):248-54. PMID- 27262759 TI - Occupation and relative risk of cutaneous squamous cell carcinoma (cSCC): A 45 year follow-up study in 4 Nordic countries. AB - BACKGROUND: The age-adjusted incidence of cutaneous squamous cell carcinoma (cSCC) in the Nordic countries has increased during the last 60 years, and the identification of occupational variation in the relative risk of cSCC may have preventive implications. OBJECTIVE: We sought to describe variation in the relative risk of cSCC between occupational categories in Finland, Iceland, Norway, and Sweden. METHODS: This is a historical prospective cohort study based on record linkages between census data for 12.9 million people and cancer registry data from 1961 to 2005. Standardized incidence ratios for cSCC were estimated for 53 occupational categories with the cSCC incidence rates for the national population of each country used as reference. RESULTS: During follow-up, 87,619 incident cases of cSCC were reported to the national cancer registries. In all countries combined, significant increased standardized incidence ratios were observed among seamen, military personnel, public safety workers, technical workers, teachers, transport workers, physicians, dentists, nurses, other health workers, religious workers, clerical workers, administrators, and sale agents (standardized incidence ratios between 1.08 and 1.77). LIMITATIONS: Information on occupation was based on 1 point in time only. CONCLUSION: The occupational variation of the relative risk of cSCC might be associated with socioeconomic factors, and to some extent to occupational exposures. PMID- 27262762 TI - Exploration of more effective neurorrhaphy in facial nerve reconstruction: A comparison focusing on the difference of neural window size and condition of the neurorrhaphy site. AB - BACKGROUND AND AIM: Various techniques have been introduced for reconstruction of the facial nerve. An improved method of neurorrhaphy to achieve satisfactory mimetic muscle function is required. We made and compared three different neurorrhaphy models to elucidate the effect of neural window size and condition of the neurorrhaphy site on axonal regeneration. METHODS: Rats were divided into four groups: group A, untreated incomplete palsy; group B, treatment by end-to side neurorrhaphy through a small perineural window; group C, treatment by side to-side neurorrhaphy through a large perineural window; and group D, treatment by side-to-side neurorrhaphy through a small perineural window. After surgery, mimetic muscle movement was evaluated. Retrograde-labeled neurons through the facial nuclei were counted, and mimetic muscle specimens were examined. The axon number was counted in nerve specimens. RESULTS: The facial palsy scores of groups B and C were significantly greater than those of groups A and D. With regard to the number of neurons at the facial nuclei, groups B and C had more neurons than groups A and D. Group D had significantly more neurons than group A. With respect to the number of axons, groups B, C, and D had significantly greater numbers than group A, but there were no significant differences between the reconstructed groups. CONCLUSIONS: Window size and condition of the neurorrhaphy site, which affected mainly the number of axons, influenced axonal regeneration in nerve reconstruction. This result indicates the possibility of obtaining a better result for facial nerve or other peripheral nerve reconstruction with a tidbit of operative artifice. PMID- 27262763 TI - Correlation of Insurance, Race, and Ethnicity with Pathologic Risk in a Controlled Retinoblastoma Cohort: A Children's Oncology Group Study. AB - PURPOSE: To determine whether insurance status, race, and ethnicity correlate with increased retinoblastoma invasiveness as a marker of both risk and time to diagnosis. DESIGN: Retrospective case-control study. PARTICIPANTS: All 203 patients from the United States enrolled in the Children's Oncology Group (COG) trial ARET0332, a study of patients with unilateral retinoblastoma requiring enucleation. MAIN OUTCOME MEASURES: All surgical specimens underwent pathologic review to determine the presence of well-defined histopathologic features correlating with a higher risk of disease progression. Insurance status, race, and ethnicity were compiled from the study record for each patient. RESULTS: On institutional pathologic review, nonprivate insurance, nonwhite race, and Hispanic ethnicity all correlated significantly with a greater rate of high-risk pathologic findings. Hispanic ethnicity remained a significant predictor on multivariate analysis. On central pathologic review, these correlations remained but did not reach statistical significance. The differences in results from institutional versus central pathologic reviews appeared to be due to a higher likelihood of patients in minority groups of being misclassified as high risk by institutional pathologists. CONCLUSIONS: In this controlled study population of patients with retinoblastoma who had central pathologic review, our findings suggest a higher rate of more advanced disease associated with nonprivate insurance, nonwhite race, and Hispanic ethnicity; these findings may be due to delays in diagnosis for these groups. Future work should use direct methods to study the impact of other variables, including English-language proficiency and socioeconomic status. Further effort also should focus on where in the diagnostic process potential delays exist, so that interventions can be designed to overcome barriers to care for these groups. In addition, potential systematic differences in pathologic reads based on demographic variables deserve further study. PMID- 27262764 TI - Five-Year Graft Survival Comparing Descemet Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty. AB - PURPOSE: To compare 5-year graft survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) in Asian eyes. DESIGN: Prospective, nested, cohort study. PARTICIPANTS: Consecutive patients who underwent DSAEK (423 eyes) or PK (405 eyes) for Fuchs' endothelial dystrophy (FED) or bullous keratopathy (BK). METHODS: Clinical data and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Registry. All surgeries were performed by the corneal surgeons at our center, which included cases performed or partially performed by corneal fellows in training under direct supervision. MAIN OUTCOME MEASURES: Five-year cumulative graft survival. RESULTS: Overall mean age was 67.8+/-9.8 years, and 50.1% of patients were men. There were no significant differences in age (P = 0.261) or gender (P = 0.78) between PK and DSAEK groups in our predominantly Chinese (76.6%) Asian cohort, with more BK compared with FED (68.1% vs. 31.9%; P < 0.001). Overall 5-year graft survival was superior for DSAEK compared with PK (79.4% vs. 66.5%; P < 0.001, log-rank test). Median 5-year percent endothelial cell density loss was significantly greater in PK compared with DSAEK (60.9% vs. 48.7%; P = 0.007). Cox regression analysis revealed that BK was a significant factor associated with graft failure (hazard ratio [HR], 3.30; 95% confidence interval [CI], 2.05-5.33; P < 0.001), and PK was more likely to fail compared with endothelial keratoplasty (HR, 1.61; 95% CI, 1.08-2.41; P = 0.02) adjusting for confounders such as recipient age, gender, and donor factors. Five-year cumulative incidence of complications such as graft rejection (P < 0.001), epitheliopathy (P < 0.001), suture-related corneal infections (P < 0.001), and wound dehiscence (P = 0.002) were greater in the PK group compared with the DSAEK group. CONCLUSIONS: In Asian eyes from the same study cohort with standardized surgical and postoperative regimes, 5-year graft survival was superior for DSAEK compared with PK in eyes with FED and BK. PMID- 27262765 TI - Fully Automated Prediction of Geographic Atrophy Growth Using Quantitative Spectral-Domain Optical Coherence Tomography Biomarkers. AB - PURPOSE: To develop a predictive model based on quantitative characteristics of geographic atrophy (GA) to estimate future potential regions of GA growth. DESIGN: Progression study and predictive model. PARTICIPANTS: One hundred eighteen spectral-domain (SD) optical coherence tomography (OCT) scans of 38 eyes in 29 patients. METHODS: Imaging features of GA quantifying its extent and location, as well as characteristics at each topographic location related to individual retinal layer thickness and reflectivity, the presence of pathologic features (like reticular pseudodrusen or loss of photoreceptors), and other known risk factors of GA growth, were extracted automatically from 118 SD OCT scans of 38 eyes from 29 patients collected over a median follow-up of 2.25 years. We developed and evaluated a model to predict the magnitude and location of GA growth at given future times using the quantitative features as predictors in 3 possible scenarios. MAIN OUTCOME MEASURES: Potential regions of GA growth. RESULTS: In descending order of out-of-bag feature importance, the most predictive SD OCT biomarkers for predicting the future regions of GA growth were thickness loss of bands 11 through 14 (5.66), reflectivity of bands 11 and 12 (5.37), thickness of reticular pseudodrusen (5.01), thickness of bands 5 through 11 (4.82), reflectivity of bands 7 through 11 (4.78), GA projection image (4.73), increased minimum retinal intensity map (4.59), and GA eccentricity (4.49). The predicted GA regions in the 3 tested scenarios resulted in a Dice index mean +/- standard deviation of 0.81+/-0.12, 0.84+/-0.10, and 0.87+/-0.06, respectively, when compared with the observed ground truth. Considering only the regions without evidence of GA at baseline, predicted regions of future GA growth showed relatively high Dice indices of 0.72+/-0.18, 0.74+/-0.17, and 0.72+/-0.22, respectively. Predictions and actual values of GA growth rate and future GA involvement in the central fovea showed high correlations. CONCLUSIONS: Experimental results demonstrated the potential of our predictive model to predict future regions where GA is likely to grow and to identify the most discriminant early indicator (thickness loss of bands 11 through 14) of regions susceptible to GA growth. PMID- 27262766 TI - Corneal Endothelium in Patients with Anterior Uveitis. AB - PURPOSE: To investigate a possible effect of intraocular inflammation on corneal endothelium by describing corneal endothelial cell density (ECD) and morphologic variables in eyes with anterior uveitis, and to investigate factors that may influence these findings. DESIGN: Cross-sectional, observational study. Observers were not masked. PARTICIPANTS: Volunteers with histories of unilateral or bilateral anterior segment inflammation (anterior, intermediate, or panuveitis); included were 52 patients (84 eyes with uveitis). METHODS: Endothelial cell density and morphologic variables of both eyes of all study participants were determined by specular microscopy; central corneal thickness was determined by ultrasound pachymetry. MAIN OUTCOME MEASURES: Central corneal ECD, coefficient of variability, percentage hexagonality, and central corneal thickness. RESULTS: Central ECD was lower among eyes that had undergone cataract or glaucoma surgery or both (n = 28; P = 0.0004). After exclusion of eyes with surgery, variables for eyes with uveitis (n = 56) were compared with 2 historical populations of normal, age-matched controls and with contralateral eyes in individuals with unilateral uveitis. Central ECD was lower in eyes with uveitis than in control eyes for all age groups (P <= 0.01 for four of six 10-year age intervals compared with the primary control group). Among patients with unilateral uveitis who had not undergone surgery in either eye (n = 12), central ECD was lower in eyes with uveitis (2324 cells/mm(2) [range, 1543-3289 cells/mm(2)]) than in contralateral eyes (2812.5 cells/mm(2) [range, 1887-3546 cells/mm(2)]; P = 0.0005), and percentage hexagonality was lower in eyes with uveitis (54% [range, 33%-66%]) than in contralateral eyes (58.5% [range, 52%-82%]; P = 0.004). There was no significant difference in central corneal thickness between eyes with and without uveitis (P = 0.27). No eyes had clinically apparent central corneal edema. Relationships remained unchanged after exclusion of eyes with herpetic anterior uveitis. Host and disease-related characteristics were evaluated as risk factors for variations in outcome measures. Central ECD was correlated to the duration of active uveitis (r = -0.41; P < 0.0001), maximum intraocular pressure during the course of disease (r = -0.40; P = 0.0002), and maximum laser flare photometry value (r = -0.26; P = 0.020). CONCLUSIONS: Observed relationships suggest that anterior segment inflammation adversely affects the corneal endothelium. Longitudinal studies are warranted to determine whether long-standing anterior uveitis increases risk of endothelial dysfunction, especially in the setting of intraocular surgery. PMID- 27262768 TI - Denoising time-resolved microscopy image sequences with singular value thresholding. AB - Time-resolved imaging in microscopy is important for the direct observation of a range of dynamic processes in both the physical and life sciences. However, the image sequences are often corrupted by noise, either as a result of high frame rates or a need to limit the radiation dose received by the sample. Here we exploit both spatial and temporal correlations using low-rank matrix recovery methods to denoise microscopy image sequences. We also make use of an unbiased risk estimator to address the issue of how much thresholding to apply in a robust and automated manner. The performance of the technique is demonstrated using simulated image sequences, as well as experimental scanning transmission electron microscopy data, where surface adatom motion and nanoparticle structural dynamics are recovered at rates of up to 32 frames per second. PMID- 27262767 TI - Evaluation of a novel high-resolution mapping technology for ablation of recurrent scar-related atrial tachycardias. AB - BACKGROUND: Rhythmia is a new technology capable of rapid and high-resolution mapping. However, its potential advantage over existing technologies in mapping complex scar-related atrial tachycardias (ATs) has not yet been evaluated. OBJECTIVE: The purpose of this study was to examine the utility of Rhythmia for mapping scar-related ATs in patients who had failed previous ablation procedure(s). METHODS: This multicenter study included 20 patients with recurrent ATs within 2 years after a previous ablation procedure (1.8 +/- 0.7 per patient). In all cases, the ATs could not be adequately mapped during the index procedure because of scar with fractionated electrograms, precluding accurate time annotation, frequent change in the tachycardia in response to pacing, and/or degeneration into atrial fibrillation. These patients underwent repeat mapping and ablation procedure with Rhythmia. RESULTS: From a total of 28 inducible ATs, 24 were successfully mapped. Eighteen ATs (75%) terminated during radiofrequency ablation and 4 (16.6%) with catheter pressure or entrainment from the site of origin or isthmus. Two ATs that were mapped to the interatrial septum slowed but did not terminate with ablation. In 21 of 24 ATs the mechanism was macroreentry, while in 3 of 24 the mechanism was focal. Interestingly, in 5 patients with previously failed ablation of an allegedly "focal" tachycardia, high-resolution mapping demonstrated macroreentrant arrhythmia. The mean mapping time was 28.6 +/ 17 minutes, and the mean radiofrequency ablation time to arrhythmia termination was 3.2 +/- 2.6 minutes. During a mean follow-up of 7.5 +/- 3.1 months, 15 of 20 patients (75%) were free of AT recurrences. CONCLUSION: The Rhythmia mapping system may be advantageous for mapping complex scar-related ATs. PMID- 27262769 TI - Repetitive reduction lead to significant elevated IL-6 and decreased IL-10 levels in femoral osteotomies: A quantitative analysis of a robot-assisted reduction process in a rat model. AB - INTRODUCTION: The field of robot-assisted fracture reduction has been developed by several research groups over more than one decade by now, with the main goals of increasing the fracture reduction accuracy. However, the influence of different reduction paths to patients' physiology is not fully known yet. The aim of our study was to compare the impacts of a robot-assisted direct reduction path versus an artificially prolonged reduction path by measuring the cytokine responses in an in vivo rat model. MATERIALS AND METHODS: Thirty-six male CD((c)) rats were assigned into three groups with an external fixator and osteotomy on the left femur. Seven days later, the robot was attached and one group was reduced in a single attempt, while the other group underwent 10 attempts by the robot. The third group was the control group without reduction. Before, and as well as 6, 24 and 48h after the reduction process blood samples were collected. IL-1, IL-6, IL-10, IL-17, and MCP-1 concentrations where analysed via ELISA or cytometric bead assay. Muscle biopsies in the osteotomy area were collected 48h after the reduction process for histological analyses. Statistical significance was set at p<=0.05. RESULTS: Analysis of the cytokines showed that the pro inflammatory cytokine IL-6 of the Ten-Attempts reduction group significantly increased 6h after reduction compared to the control group. IL-6 further showed markedly elevated levels 6h after surgery in the Ten-Attempts reduction group compared to the Single-Attempt reduction group. On the anti-inflammatory side, IL 10 showed a significant decrease in the Ten-Attempts reduction group 6h after reduction compared to the Single-Attempt reduction and control group. Muscle biopsies showed a significant increase of pathological changes in both reduction groups and an increase in the severity of bleedings of the Ten-Attempts reduction group compared to the Single-Attempt reduction and control group. CONCLUSION: A direct and gentle reduction procedure as feasible by the aid of a robot is preferable over a prolonged reduction in terms of cytokine response and tissue changes. PMID- 27262770 TI - Unplanned 30-day readmissions in orthopaedic trauma. AB - INTRODUCTION: 30-day readmission is increasingly used as a hospital quality metric. The objective of this study was to describe the patient factors associated with unplanned 30-day hospital readmission of orthopaedic trauma patients. METHODS: A statewide observational study was undertaken using data from all acute hospitals in California. All hospital inpatients with a primary diagnosis of fracture or dislocation (ICD-9-CM codes 800-829) were included, except for those with isolated injuries to the skull, face, or ribs. The primary outcome measure was unplanned 30-day readmission to any hospital in California. RESULTS: 416,568 trauma admissions were available for analysis. The overall readmission rate was 6.5%, and 27.3% of readmitted patients presented to a different hospital. Factors significantly associated with readmission were male sex (OR 1.23, 95% CI 1.19-1.27), age 46-65 (2.61 [2.27-2.99]), black race (1.19 [1.11-1.27]), entitlement to publicly funded healthcare (1.38 [1.25-1.52]), Charlson Comorbidity Index >=2 (1.84 [1.79-1.90]), discharge against medical advice (3.13 [2.67-3.68]), and spinal fracture (1.42 [1.34-1.49]). Major reasons for readmission included: cardiopulmonary disease (25.6%), infections (20.1%), musculoskeletal problems (18.1%), and procedural complications (12.0%). CONCLUSIONS: Many orthopaedic trauma readmissions are potentially unrelated to the initial hospitalization. Penalties for unplanned readmissions risk penalizing hospitals that serve disadvantaged communities and treat a high proportion of trauma patients. PMID- 27262771 TI - A new technique to close open abdomen using negative pressure therapy and elastic gums. PMID- 27262772 TI - Incidence and risk factors for removal of an internal fixation following surgery for ankle fracture: A retrospective cohort study of 997 patients. AB - BACKGROUND: Implant removal in ankle fractures treated by open reduction and fixation is often based on diffuse complaints. This study determined the incidence of implant removal and identified risk factors for two principal causes for removal: complaints and surgical site infection (SSI). METHODS: Retrospective cohort study involving 997 patients operated on 2009-2011 with follow-up through to 2013. The incidence of implant removal was analysed using competing risk analysis. Risk factors for implant removal were assessed using cause-specific hazard ratios (HRs) from a Cox regression analysis. RESULTS: The mean age at surgery was 51.6 years, 550 (55%) of the patients were female, and 170 patients (17%) had implant removal: 144 due to complaints and 26 due to infection. Multivariable HRs for implant removal due to complaints were 0.70 for male sex (p=0.047), 0.79 for each 10-year increase in age (p<0.001), 0.70 for treatment with a syndesmosis screw (p=0.038), and 1.09 for each 15-min increase in operation duration (p=0.007). HRs for hardware removal due to infection were 1.42 for each 10-year increase in age (p=0.006) and 3.15 for current smoking (p=0.005). CONCLUSION: In total 17% of patients had implant removal after open reduction and fixation; the majority because of subjective complaints. The risk factors for implant removal were different for removal due to complaints than for those removed due to infection. This information may be used to inform patients about the risk and risk factors for future implant removal. PMID- 27262773 TI - Efficacy of knee joint aspiration in patients with acute ACL injury in the emergency department. AB - PURPOSE: To evaluate the influence of joint aspiration on the sensitivity of physical examination for diagnosing acute anterior cruciate ligament (ACL) lesion in the second outpatient-department (OPD) follow-up referred from emergency department (ED). METHODS: This retrospective study included sixty patients underwent ACL reconstruction with initial visit at ED. They were divided into two groups based on the presence or absence of joint aspiration at ED. All participants were referred to second OPD follow-up within 7-14days after the injury. Clinical manifestation (including visual analogue scale (VAS) for pain, range of motion (ROM), and severity of knee effusion) and physical examination (Lachman test and pivot shift test) were checked in ED and the second OPD follow up. RESULTS: The group of patients with joint aspiration (G1) showed substantial decreases in mean values of VAS for pain (p=0.005), ROM (p=0.001), and effusion level (p<0.001), even higher VAS and effusion level and lower ROM at the initial visit of ED than the other group (G2). The sensitivity of positive Lachman and pivot shift test was significantly (p<0.05) increased following knee joint aspiration. Positive Lachman test was recorded at 76.5% in the second follow-up in G1, which was significantly (p=0.047) higher than that (47.6%) in G2. The percentage of positive pivot shift test was recorded at 76.5% in the second follow-up in G1, which as significantly (p<0.001) higher than that (31.0%) in G2. CONCLUSIONS: Knee joint aspiration in acute ACL injury with suspected hemarthrosis could be considered as a diagnostic procedure. Joint aspiration in early medical attendance might be able to lower pain scores or raise the sensitivity of physical examination for diagnosing acute ACL injury at follow up visit in orthopedic outpatient department. LEVEL OF EVIDENCE: Retrospective cohort study III. PMID- 27262774 TI - Treatment of dysphasia with rTMS and language therapy after childhood stroke: Multimodal imaging of plastic change. AB - Expressive dysphasia accompanies left inferior frontal gyrus (IFG/Broca) injury. Recovery may relate to interhemispheric balance with homologous, contralesional IFG but is unexplored in children. We evaluated effects of inhibitory rTMS to contralesional IFG combined with intensive speech therapy (SLT). A 15year-old, right-handed male incurred a left middle cerebral artery stroke. After 30months, severe non-fluent dysphasia impacted quality of life. Language networks, neuronal metabolism and white matter pathways were explored using MRI. Language function was measured longitudinally. An intensive SLT program was combined with contralesional inhibitory rTMS of right pars triangularis. Procedures were well tolerated. Language function improved persisting to four months. Post-treatment fMRI demonstrated increased left perilesional IFG activations and connectivity at rest. Bilateral changes in inositol and glutamate metabolism were observed. Contralesional, inhibitory rTMS appears safe in childhood stroke-induced dysphasia. We observed clinically significant improvements after SLT coupled with rTMS. Advanced neuroimaging can evaluate intervention-induced plasticity. PMID- 27262775 TI - Clinical effectiveness of bisphosphonates for the prevention of fragility fractures: A systematic review and network meta-analysis. AB - OBJECTIVES: To assess the relative efficacy of bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid) for the treatment of osteoporosis using network meta-analysis (NMA). METHODS: A systematic review of the literature was conducted using PRISMA guidelines. A network meta-analysis was used to determine the relative efficacy of treatments on four fracture outcomes (vertebral, non-vertebral, hip and wrist) and percentage change in femoral neck bone mineral density (BMD). Treatment effects were modelled using an exchangeable treatment effects model. Heterogeneity in treatment effects was explored by considering potential treatment effect modifiers using meta-regression. Where appropriate, inconsistency between direct and indirect evidence was assessed using node-splitting. RESULTS: 46 randomised controlled trials (RCTs) were identified. Twenty seven RCTs provided fracture data and 35 RCTs provided BMD data for analysis. Zoledronic acid was associated with the greatest treatment effect on vertebral fractures (HR 0.41, 95% CrI: 0.28, 0.56) and percentage change in BMD (3.21, 95%: CrI 2.52, 3.86) compared to placebo. The greatest treatment effect on non-vertebral and wrist fractures was given by risedronate (HR 0.72, 95%: CrI 0.53, 0.89 and HR 0.77, 95%: CrI 0.44, 1.24, respectively). For hip fractures the greatest treatment effect was given by alendronate (HR 0.78, 95% CrI: 0.44, 1.30). CONCLUSIONS: All treatments examined were associated with beneficial effects on fractures and femoral neck BMD relative to placebo. For vertebral fractures and percentage change in femoral neck BMD the treatment effects were statistically significant for all treatments. Pairwise comparisons between treatments indicated that no active treatment was statistically significantly more effective than any other active treatment for fracture outcomes. There was some heterogeneity in treatment effects between studies suggesting differential treatment effects according to study characteristics; however, there was no evidence of differential treatment effects with respect to gender and age. PMID- 27262777 TI - Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength. AB - Mammalian target of rapamycin (mTOR) is a Ser/Thr kinase conserved through evolution that coordinates extra cellular signals associated with cell growth. Main functions of mTOR present in the form of two complexes, namely mTORC1 and mTORC2, which are distinct in their unique components, raptor and rictor. In the current study, using a Cre/loxp system, we found an anabolic effect of mTORC2 signaling on skeleton. Osteoblast differentiation was reduced, with down regulation of mTORC2 signaling activity in primary cultures of osteoblasts that did not contain rictor. Mice with a specific deletion of rictor in mature osteoblasts showed a significant reduction in lean mass and bone mineral density by dual energy x-ray absorptiometry analysis. Micro-computed tomography, histomorphometric, and molecular biological analyses revealed a marked impairment of the cortical bone mass and microarchitecture, as well as minor changes in trabecular bone, of the Rictorob(-/-) mice. Cortical bone mass and thickness of the femoral mid-shaft were dramatically reduced, with unusual increases in porosity and marrow area in Rictorob(-/-) mice. Thinner trabeculae were found in the L4 vertebrae with relatively normal structural indices of trabecular numbers and separation. A lower rate of bone turnover was observed, as the consequence of the decreased individual osteoblast activity and bone resorption. Furthermore, these changes were associated with significantly decreased bone biomechanical properties. In conclusion, expression of rictor in osteoblasts is essential for the maintenance of normal bone remodeling and microarchitecture, especially for the maintenance of the cortical bone. PMID- 27262778 TI - P2 receptors in cancer progression and metastatic spreading. AB - Tumor microenvironment is nucleoside and nucleotide rich. Adenosine is a key determinant of the highly immunosuppressive tumor interstitium. Extracellular ATP also affects anti-tumor immunity, albeit its effects on host-tumor interaction are incompletely understood. We give here an overview of recent literature covering the role of nucleotide-selective (P2) plasma membrane receptors in tumor growth and progression. P2 receptors are expressed on both host and cancer cells, where depending on the receptor subtype, the inflammatory infiltrate and the tumor cell type they may drive an anti-tumor response or promote tumor progression. It is anticipated that knowledge of the pharmacology, biochemistry and functional activity of the P2 receptors will allow a better understanding of host-tumor interaction and the development of innovative anti-cancer therapy. PMID- 27262776 TI - Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma. AB - Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibration (LIV), a means to deliver mechanical signals, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n=25) were injected with human-myeloma cells, while 8 (AC) were saline-injected. Myeloma-injected mice (LIV; n=13) were subjected to daily-mechanical loading (15min/d; 0.3g @ 90Hz) while 12 (MM) were sham-handled. At 8w, femurs had 86% less trabecular bone volume fraction (BV/TV) in MM than in AC, yet only a 21% decrease in LIV was observed in comparison to AC, reflecting a 76% increase versus MM. Cortical BV was 21% and 15% lower in MM and LIV, respectively, than in AC; LIV showing 30% improvement over MM. Similar outcomes were observed in the axial skeleton, showing a 35% loss in MM with a 27% improved retention of bone in the L5 of LIV treated mice as compared to MM. Transcortical-perforations in the femur from myeloma-induced osteolysis were 9* higher in MM versus AC, reduced by 57% in LIV. Serum-TRACP5b, 61% greater in MM versus AC, rose by 33% in LIV compared to AC, a 45% reduction in activity when compared to MM. Histomorphometric analyses of femoral trabecular bone demonstrated a 70% elevation in eroded surfaces of MM versus AC, while measures in LIV were 58% below those in MM. 72% of marrow in the femur of MM mice contained tumor, contrasted by a 31% lower burden in LIV. MM mice (42%) presented advanced-stage necrosis of tibial marrow while present in just 8% of LIV. Myeloma infiltration inversely correlated to measures of bone quality, while LIV slowed the systemic, myeloma-associated decline in bone quality and inhibited tumor progression through the hindlimbs. PMID- 27262780 TI - Genetically Informed Medicine. PMID- 27262779 TI - YAP/TAZ as therapeutic targets in cancer. AB - The biology and regulation of YAP and TAZ, two closely related transcriptional regulators, are receiving increasing attention owing to their fundamental roles in organ growth, tissue repair and cancer. In particular, the widespread activation of YAP/TAZ in carcinomas, and the crucial role of YAP/TAZ activation for many 'hallmarks' of cancer are indicating YAP/TAZ as prime targets for designing anti-cancer drugs. Here, we start from the known modalities to regulate YAP/TAZ to highlight possible routes of therapeutic intervention. PMID- 27262782 TI - Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants After Cardioversion for Nonvalvular Atrial Fibrillation. AB - BACKGROUND: Non-vitamin K oral anticoagulants (NOACs) are proven alternatives to vitamin K antagonists (VKAs) for the prevention of thromboembolism in patients with nonvalvular atrial fibrillation. However, there are few data on the efficacy and safety of NOAC therapy after cardioversion, where the risk of thromboembolic events is heightened. METHODS: We performed a random-effects meta-analysis of patients who underwent both electrical and pharmacologic cardioversion for atrial fibrillation in the RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48, and X-VeRT trials. We assessed Mantel-Haenszel pooled estimates of risk ratio (RR) and 95% confidence intervals (CIs) for stroke/systemic embolism and major bleeding at <=42 days of follow-up. RESULTS: The analysis pooled 3949 patients in whom a total of 4900 cardioversions for atrial fibrillation were performed. Compared with VKAs, NOAC therapy was associated with a similar risk of stroke/systemic embolism (RR 0.84; 95% CI, 0.34-2.04) and major bleeding (RR 1.12; 95% CI, 0.52 2.42); no significant statistical heterogeneity was found among studies (Cochrane Q P = .59, I(2) = 0% for stroke/systemic embolism; P = .47; I(2) = 0% for major bleeding). CONCLUSIONS: The short-term incidences of thromboembolic and major hemorrhagic events after cardioversion on NOACs were low and comparable to those observed on dose-adjusted VKA therapy. Non-vitamin K oral anticoagulants are a reasonable alternative to VKAs in patients undergoing cardioversion. PMID- 27262781 TI - Renin-Angiotensin System Inhibition and Lower 30-Day All-Cause Readmission in Medicare Beneficiaries with Heart Failure. AB - BACKGROUND: Heart failure is the leading cause for 30-day all-cause readmission, the reduction of which is a goal of the Affordable Care Act. There is a growing interest in understanding the impact of evidence-based heart failure therapy on 30-day all-cause readmission. In the current study, we examined the impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI ARBs) on 30-day all-cause readmission in heart failure. METHODS: Of the 1384 hospitalized Medicare beneficiaries with heart failure and left ventricular ejection fraction <45% discharged alive from 106 Alabama hospitals (1998-2001) without prior ACEI-ARB use and without known contraindications to ACEI-ARB use; 734 received new predischarge prescriptions for these drugs. Using propensity scores for ACEI-ARB initiation, we assembled a matched cohort of 477 pairs of patients balanced on 32 baseline characteristics (mean age 75 years, 46% women, 26% African American). RESULTS: Thirty-day all-cause readmissions occurred in 18% and 24% of matched patients receiving and not receiving ACEI-ARBs, respectively (hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.56-0.97; P = .030). ACEI ARB use was also associated with lower risk of 30-day all-cause mortality (HR 0.56; 95% CI, 0.33-0.98; P = .041) and of the combined endpoint of 30-day all cause readmission or 30-day all-cause mortality (HR 0.73; 95% CI, 0.56-0.94; P = .017). All associations remained significant at 1 year post discharge. CONCLUSIONS: Among hospitalized patients with heart failure and reduced ejection fraction, the use of ACEI-ARBs was associated with a significantly lower risk of 30-day all-cause readmission and 30-day all-cause mortality; both beneficial associations persisted during long-term follow-up. PMID- 27262783 TI - Comparing glutamatergic neuron population in the mediodorsal thalamic nucleus of genetic absence epilepsy rats from strasbourg (GAERS) and normal control Wistar rats. AB - An imbalance between GABAergic inhibition and glutamatergic excitation is suspected to play a role in the genesis of epileptic processes. In the present study we quantified the number of glutamate+ve neurons in the mediodorsal thalamic nucleus (MD) of genetic absence epilepsy rats from Strasbourg (GAERS) and compared these with values for normal Wistar rats. The MD thalamic nucleus was removed from each animal and the glutamatergic neurons were labelled using light-microscopy glutamate immunohistochemistry. The disector method was used to quantify the glutamate+ve neurons in the MD thalamic nucleus of GAERS and Wistar rats. The data were statistically analyzed. In the Wistar animals glutamate+ve neurons formed 89% and in GAERS 92.3% of the total neurons in 1000MUm3 of MD thalamic nucleus. In GAERS glutamate+ve neurons showed statistically significant increase in the MD thalamic nucleus compared to Wistar animals. In Wistar animals the glutamate-ve neurons formed 11% and in GAERS 7.7% of the total neurons in 1000MUm3 of MD thalamic. No significant difference was observed in glutamate-ve neurons between the two strains. The average diameter of glutamate+ve neurons showed no significance, while glutamate-ve neurons were significant between the two strains. The results of the present study, on genetic absence epilepsy model, GAERS, confirms the role of MD thalamic nucleus in chemically induced absence epilepsy. PMID- 27262784 TI - Consumptive water footprint and virtual water trade scenarios for China - With a focus on crop production, consumption and trade. AB - The study assesses green and blue water footprints (WFs) and virtual water (VW) trade in China under alternative scenarios for 2030 and 2050, with a focus on crop production, consumption and trade. We consider five driving factors of change: climate, harvested crop area, technology, diet, and population. Four scenarios (S1-S4) are constructed by making use of three of IPCC's shared socio economic pathways (SSP1-SSP3) and two of IPCC's representative concentration pathways (RCP 2.6 and RCP 8.5) and taking 2005 as the baseline year. Results show that, across the four scenarios and for most crops, the green and blue WFs per tonne will decrease compared to the baseline year, due to the projected crop yield increase, which is driven by the higher precipitation and CO2 concentration under the two RCPs and the foreseen uptake of better technology. The WF per capita related to food consumption decreases in all scenarios. Changing to the less-meat diet can generate a reduction in the WF of food consumption of 44% by 2050. In all scenarios, as a result of the projected increase in crop yields and thus overall growth in crop production, China will reverse its role from net VW importer to net VW exporter. However, China will remain a big net VW importer related to soybean, which accounts for 5% of the WF of Chinese food consumption (in S1) by 2050. All scenarios show that China could attain a high degree of food self-sufficiency while simultaneously reducing water consumption in agriculture. However, the premise of realizing the presented scenarios is smart water and cropland management, effective and coherent policies on water, agriculture and infrastructure, and, as in scenario S1, a shift to a diet containing less meat. PMID- 27262786 TI - Propelling plastics into the circular economy - weeding out the toxics first. AB - The Stockholm Convention bans toxic chemicals on its persistent organic pollutants (POPs) list in order to promote cleaner production and prevent POPs accumulation in the global environment. The original 'dirty dozen' set of POPs has been expanded to include some of the brominated diphenyl ether flame retardants (POP-BDEs). In addition to cleaner production, there is an urgent need for increased resource efficiency to address the finite amount of raw materials on Earth. Recycling plastic enhances resource efficiency and is part of the circular economy approach, but how clean are the materials we are recycling? With the help of a new screening method and detailed analyses, we set out to investigate where these largely obsolete BDEs were showing up in Dutch automotive and electronics waste streams, calculate mass flows and determine to what extent they are entering the new product chains. Our study revealed that banned BDEs and other toxic flame retardants are found at high concentrations in certain plastic materials destined for recycling markets. They were also found in a variety of new consumer products, including children's toys. A mass flow analysis showed that 22% of all the POP-BDE in waste electrical and electronic equipment (WEEE) is expected to end up in recycled plastics because these toxic, bioaccumulative and persistent substances are currently not effectively separated out of plastic waste streams. In the automotive sector, this is 14%, while an additional 19% is expected to end up in second-hand parts (reuse). These results raise the issue of delicate trade-offs between consumer safety/cleaner production and resource efficiency. As petroleum intensive materials, plastic products ought to be repaired, reused, remanufactured and recycled, making good use of the 'inner circles' of the circular economy. Keeping hazardous substances - whether they are well known POPs or emerging contaminants - out of products and plastic waste streams could make these cycles work better for businesses, people and nature. PMID- 27262787 TI - Two new cyclopentenones and a new furanone from Baeckea frutescens and their cytotoxicities. AB - Two new cyclopentenones, frutescencenones A (1) and B (2), and a new furanone derivative, frutescencenone C (3), together with two known cyclopentenones (4 and 5), were isolated from the leaves of Baeckea frutescens. Their structures were deduced by comprehensive spectroscopic analyses, including 1D and 2D NMR, and HREIMS data. Frutescencenone A (1) showed moderate growth inhibitory activity against human lung A549, pancreatic PSN-1, and breast MDA-MB-231 cancer cell lines, with IC50 values of 36.3MUM, 38.2MUM, and 29.3MUM, respectively. In contrast, frutescencenone C (3) showed selective cytotoxic activity against PSN 1, with an IC50 value of 20.1MUM. PMID- 27262785 TI - Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study. AB - BACKGROUND: ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. AIMS: To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. MATERIALS AND METHODS: Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008-2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N=1313) (mean 3.9ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20months of age (N=1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. RESULTS: Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (p<0.001 to 0.013). One SNP (ABCC1 rs11075290) was also significantly associated with neurodevelopment; children born to mothers with rs11075290 CC genotype (mean hair Hg 3.6ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7ppm) while children with the CT genotype (mean hair Hg 4.0ppm) had intermediate BSID scores. DISCUSSION: Genetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated. PMID- 27262788 TI - Melatonin protects female rats against steatosis and liver oxidative stress induced by oestrogen deficiency. AB - AIMS: Melatonin has been shown to protect cells against oxidative and inflammatory damage via endocrine, paracrine and autocrine actions. Postmenopausal condition is associated with a high incidence of many features of metabolic syndrome including obesity, steatosis and liver oxidative injuries. The aim of this work was to investigate whether treatment with melatonin improves metabolic disturbances associated with oestrogen deficiency in ovariectomised (OVX) rats. MAIN METHODS: OVX and control (CON) female rats were treated with melatonin (10mg/kg*day for 3weeks, p.o.). Body weight gain, adiposity index, plasma biochemical parameters, liver lipid content, hepatic mitochondrial respiration, fatty acid oxidation and mitochondrial H2O2 generation and the activity of the most important enzymatic and non-enzymatic reactive oxygen species (ROS) scavenger systems were measured. KEY FINDINGS: In OVX rats, melatonin suppressed lipid accumulation and cellular oxidative stress in the liver. There was a reduction in the levels of carbonylated proteins in the mitochondria and cytosol, reduction in the malondialdehyde contents in the liver homogenates, stimulation of cytosolic glutathione peroxidase and glutathione reductase activities and restoration of reduced glutathione contents to normal levels. SIGNIFICANCE: Exogenous melatonin protects the liver of OVX rats against steatosis and cellular oxidative stress, possibly via activation of antioxidant enzymes related to glutathione metabolism and by a direct radical scavenging activity. PMID- 27262789 TI - The Third Tomoh Masaki Award (2015). PMID- 27262791 TI - Introduction. PMID- 27262790 TI - Lycium barbarum polysaccharides ameliorates renal injury and inflammatory reaction in alloxan-induced diabetic nephropathy rabbits. AB - AIMS: This study was aimed to investigate the effect of Lycium barbarum polysaccharides (LBP) on renal function and inflammatory reaction in rabbits with diabetic nephropathy. MAIN METHODS: Diabetes was induced by injecting alloxan (ALX). Japanese male white rabbits were randomly assigned into 5 groups: normal control group, diabetic nephropathy (DN) model group, LBP prevention group, positive control group and LBP treatment group. LBP (10mg/kg) was given to the LBP prevention group after diabetes mellitus (DM) model succeeded for 12weeks and to the LBP treatment group after DN model succeeded for 4weeks. Telmisartan (3.7mg/kg) was given to the positive group after DN model succeeded for 4weeks, and the same volume of balanced saline was given to the normal group and DN group for 12weeks. Urea nitrogen (BUN), creatinine (SCr), and C-reaction protein (CRP) in serum were detected at the end of the 12th week. The expression of MCP-1 mRNA and ICAM-1 mRNA extracted from cortex were detected by RT-PCR. Western blot analysis was carried out to examine NF-kappaB p65 protein expression. KEY FINDINGS: LBP improves the renal function and alleviates the inflammatory reaction in the kidneys of diabetic rabbits. In addition, the prevention effect of LBP is better than the treatment effect of LBP. SIGNIFICANCE: LBP has obvious protective effect on the diabetic nephropathy rabbits' renal function and postpones the appearance and development of DN. The mechanisms may be related to the reduction the expression of MCP-1mRNA and ICAM-1mRNA by restraining the expression of NF-kappaB and AngII. PMID- 27262792 TI - Mechanisms of NF-kappaB deregulation in lymphoid malignancies. AB - Deregulations promoting constitutive activation of canonical and non-canonical NF kappaB signaling are a common feature of many lymphoid malignancies. Due to their cellular origin and the pivotal role of NF-kappaB for the normal function of B lymphocytes, B-cell malignancies are particularly prone to genetic aberrations that affect the pathway. Key positive regulators of NF-kappaB signaling can act as oncogenes that are often prone to chromosomal translocation, amplifications or activating mutations. Negative regulators of NF-kappaB have tumor suppressor functions and are frequently inactivated either by genomic deletions or point mutations. Whereas some aberrations are found in a variety of different lymphoid malignancies, some oncogenic alterations are very restricted to distinct lymphoma subsets, reflecting the clonal and cellular origin of specific lymphoma entities. NF-kappaB activation in many lymphoma cells is also driven by the microenvironment or chronic signaling that does not rely on genetic alterations. A number of drugs that target the NF-kappaB pathway are in preclinical or clinical development, revealing that there will be new options for therapies in the future. Since each lymphoma entity utilizes distinct mechanisms to activate NF-kappaB, a major challenge is to elucidate the exact pathological processes in order to faithfully predict clinical responses to the different therapeutic approaches. PMID- 27262793 TI - Non-canonical programmed cell death mechanisms triggered by natural compounds. AB - Natural compounds are the fundament of pharmacological treatments and more than 50% of all anticancer drugs are of natural origins or at least derived from scaffolds present in Nature. Over the last 25 years, molecular mechanisms triggered by natural anticancer compounds were investigated. Emerging research showed that molecules of natural origins are useful for both preventive and therapeutic purposes by targeting essential hallmarks and enabling characteristics described by Hanahan and Weinberg. Moreover, natural compounds were able to change the differentiation status of selected cell types. One of the earliest response of cells treated by pharmacologically active compounds is the change of its morphology leading to ultra-structural perturbations: changes in membrane composition, cytoskeleton integrity, alterations of the endoplasmic reticulum, mitochondria and of the nucleus lead to formation of morphological alterations that are a characteristic of both compound and cancer type preceding cell death. Apoptosis and autophagy were traditionally considered as the most prominent cell death or cell death-related mechanisms. By now multiple other cell death modalities were described and most likely involved in response to chemotherapeutic treatment. It can be hypothesized that especially necrosis related phenotypes triggered by various treatments or evolving from apoptotic or autophagic mechanisms, provide a more efficient therapeutic outcome depending on cancer type and genetic phenotype of the patient. In fact, the recent discovery of multiple regulated forms of necrosis and the initial elucidation of the corresponding cell signaling pathways appear nowadays as important tools to clarify the immunogenic potential of non-canonical forms of cell death induction. PMID- 27262794 TI - Epicardial adipose tissue volume a diagnostic study for independent predicting disorder of circadian rhythm of blood pressure in patients with essential hypertension. AB - The aim of the study was to determine whether epicardial adipose tissue volume (EATV), a new cardiometabolic risk factor, is associated with circadian changes of blood pressure (BP) in patients with newly diagnosed essential hypertension. Ninety patients with newly diagnosed essential hypertension underwent ambulatory blood pressure monitoring for 24 h. EATV was measured using cardiac computed tomography. These patients were categorized into three groups according to their BP patterns (group 1, n=46, dipper hypertension, also called normal pattern; group 2, n=24, non-dipper hypertension; group 3, n=20, anti-dipper hypertension; group 2 and 3 are also called abnormal pattern). Data were collected retrospectively and compared between hypertensive patients with normal pattern and abnormal pattern. The normal pattern hypertensive patient had significant lower mean EATV and BP ((EATV, 91.3+/-29.4 cm3) than those of abnormal pattern patients including group 2 (EATV, 116.2+/-31.06cm3, <0.01) and group 3 (EATV, 124.8+/-28.5cm3, P<0.01). Mean systolic BP over 24 h (BPs24) and mean diastolic BP over 24 h (BPd24) of group 1 (BPs24, 135.7 +/- 12.6 mmHg; BPd24, 83.6 +/- 10.6 mmHg) were significantly lower than those of group 2 (BPs24, 150.1+/- 17.6 mmHg, P<0.01; BPd24, 93.2 +/- 16.5 mmHg, P<0.01) and group 3 (BPs24, 154.1 +/- 16.6mmHg, P<0.01; BPd24, 93.8 +/- 17.5 mmHg; P<0.01). Bivariate correlation analysis showed that correlation coefficient of EATV with abnormal blood pressure mode was 0.500 (p<0.001), partial correlation coefficient after adjustment for waist circumference and body mass index was 0.469 (p<0.001). When multivariate backward logistic regression analysis was performed to assess the correlation of BP pattern with EAT volume, it showed that the prevalence of abnormal BP pattern (non-dipper and anti-dipper BP pattern) increased by 1.54 times after adjusting for age and gender per additional 10 cm3 of EAT volume. Receiver operating characteristic curve for EAT alone indicated that the cutoff value of 95.17cm3 had the best performance in predicting abnormal BP pattern with a sensitivity of 75.0% and a specificity of 72.7%. EATV was elevated in newly diagnosed and untreated patients with non-dipper hypertension and anti-dipper hypertension. EATV measured by cardiac computed tomography can be used to indicate the increased risk of circadian rhythm of blood pressure. PMID- 27262796 TI - Mapping of protein-protein interaction network of Alexander disease. AB - Alexander disease (ALXD) is slowly progressive neurodegenerative disorder which affects white matter of the central nervous system. The main cause of disorder is mutation in GFAP gene and mutation in some other genes were also reported. This study was aimed at getting a better insight into ALXD pathogenesis and identifying the important functional and highly interconnected nodes in human protein interaction network, identifying the important sub-networks in the system could be helpful in understanding the underlying molecular mechanism. The topological analysis of human protein interaction network strategy to identify highly interconnected sub-network modules from which six proteins are found i.e. GFAP, PLEC, CRYAB, NDUFV1, CASP3 and MAPK14 plays important role in disease. Further, the enrichment analysis of interaction network identifies crucial pathways in which most of the diseased proteins overlaps. Through system biology approach, the undirected human protein interaction network of ALXD is buildup with the help of Cytoscape tool and its various plugins helps to investigate network further. The systematic approach suggests the finding of previously known proteins, GFAP, PLEC, CRYAB, NDUFV1, CASP3 and MAPK14 can be used as a drug targets and potential treatment discovered also enrichment analysis will provide guidance for the future study on Alexander disease. PMID- 27262795 TI - Mutagenic, antimutagenic, antioxidant, anti-lipoxygenase and antimicrobial activities of Scandix pecten-veneris L. AB - Scandix pecten-veneris L. or Shepherd's-needle is a weed species used in some countries for medicinal purposes. In this study S. pecten-veneris leaves were shade dried, powdered and extracted with methanol. The purpose of this study was to assay the in vitro mutagenic, antimutagenic, antioxidant, antilipoxygenase and antimicrobial activities of S. pecten-veneris leaf extract. The methanolic extract indicated no mutagenicity when tested with Salmonella typhimurium strains TA98 and TA100. Antimutagenic activity was reported with inhibition of mutagenicity in a concentration dependent fashion. The methanolic extract demonstrated antioxidant activity in the DPPH radical-scavenging test (IC50 = 4.57 mg/mL), comparable to ascorbic acid and BHT. Moreover, the extract presented a remarkable and potent inhibition against soybean lipoxygenase (IC50 = 641.57 ug/mL). The methanolic extract was examined for its antimicrobial powers against four different bacteria with MIC values >100. Our results introduced this plant as a useful factor for the treatment of cancer, inflammatory and infectious diseases. PMID- 27262797 TI - Some heavy metals in the muscle of Capoeta trutta: risk assessment for the consumers. AB - This study was carried out to detect the concentrations of some heavy metals (copper, iron, zinc, cadmium and chromium) in the muscle of Capoeta trutta (Heckel, 1843) and in their surrounding water in order to study the potential human risk of consumption. The relationship between the heavy metal load of fish and some of their biological aspects (weight, length and sex) was also examined. In addition, the accumulation factors of heavy metals in this species were determined. The concentrations of Cu, Fe, Zn, Cd and Cr in water and muscle samples were analysed using ICP. Cu, Zn and Fe were detected in all samples, but Cd and Cr were not found in detectable levels. The results showed that heavy metals accumulation in muscle of fish was higher than that in the water. It was found that the level of heavy metals in the muscle of fish showed differences according to weight, length and sex of fish. PMID- 27262798 TI - Argatroban more effectively inhibits the thrombin activity in synovial fluid than naturally occurring thrombin inhibitors. AB - The purpose of this study was to clarify the precise effect of argatroban on the inhibition of cytokine secretion induced by thrombin on synovial cells. The efficiency of thrombin inactivation by thrombin inhibitors was evaluated in human synovial fluids (SFs). In SFs from 13 osteoarthritis (OA) and 11 rheumatoid arthritis (RA) patients, thrombin, Factor Xa (FXa), plasmin activity, IL-6, MMP 3, VEGF, and D-dimer concentrations were measured. Tissue factor (TF) activity or IL-6, MMP-3, and VEGF secretion of human synovial cells with or without thrombin and argatroban were measured. The efficiency of thrombin inactivation in SFs was compared for thrombin inhibitors: argatroban, antithrombin III (ATIII), or heparin cofactor II (HCII). In SFs, thrombin, FXa, plasmin, D-dimer, IL-6, and MMP-3 were significantly higher in RA than in OA. In synovial cell experiments, TNF-alpha and thrombin enhanced TF activity on the cell surface, and IL-6, MMP-3, and VEGF secretion were enhanced by thrombin. Increased TF activity, and IL-6, MMP-3, and VEGF secretion induced by thrombin were inhibited by argatroban. In SFs, argatroban inactivated thrombin more effectively than ATIII or HCII. Since thrombin plays an important role in the disease activity of OA and RA, it is a potential therapeutic molecular target. Argatroban was the most effective anticoagulant to inhibit thrombin activity in SF. Intra-articular injection is ideal administration because it can deliver high dose of argatroban without high risk of systematic complication. PMID- 27262799 TI - TSG-6 treatment promoted apoptosis in human fibroblasts of pathological scar. AB - Pathological scars are characterized by excessive fibrosis and extracellular matrix (ECM) deposition and can be functionally and cosmetically problematic; however, there are few satisfactory treatments for controlling pathological scars. The proliferation of fibroblast during wound healing play an important role in pathologic scar formation. Therefore, the promotion of fibroblast apoptosis may be a new point to inhibit scar formation. In this study, pathological scar fibroblasts were treated with TSG-6 in monolayer culture and subjected to examination for cell apoptosis and associated proteins involved in cell apoptosis. We found that TSG-6 significantly promoted cell apoptosis of pathological scar fibroblasts. Meanwhile, expression level of cell apoptosis related cytokine protein Bax increased and cell proliferation related signal transduction pathways are blocked since the expression level of Bcl-2 was decreased. PMID- 27262800 TI - The individual or combinational effects of Hesperetin and Letrozole on the activity and expression of aromatase in MCF-7 cells. AB - Aromatase catalyzes the last and rate-limiting step in estrogen biosynthesis. Inhibition of estrogen production is a common strategy for breast cancer treatment. Citrus flavonoids have been confirmed to exhibit efficacious biological activities, particularly in cancer therapy. This study was carried out to investigate the effect of hesperetin on the activity and expression of aromatase and compare this property with letrozole as an aromatase inhibitor in MCF-7 breast cancer cell line. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays in this study demonstrated that hesperetin at a concentration of 200 MUM decreased cell viability in a time dependent manner (P<0.05). Aromatase activity assay, based on 17beta-Estradiol (E2) production from testosterone, revealed that hesperetin had no effect. Real-time PCR results indicated that treatment with 1MUM concentration of hesperetin for 48 h significantly decreased relative aromatase expression (P =0.004). Combination of letrozole and hesperetin also had no effect on aromatase. The changes in activity paralleled the expression of aromatase. Likely, the reduction in aromatase activity was delayed in time along with the reduction in expression ratio; however additional studies are needed to confirm this. In conclusion, the present study showed that hesperetin could decrease expression of aromatase at low concentrations in MCF-7 breast cancer cells. PMID- 27262801 TI - siRNA-mediated inhibition of survivin gene enhances the anti-cancer effect of etoposide in U-937 acute myeloid leukemia cells. AB - Acute myeloid leukemia (AML) is one of the most frequent types of leukemia which mostly affects adult people. Resistance to therapeutic drugs is considered as a major clinical concern resulting in a weaker response to chemotherapy, disease relapse and decreased survival rate. Survivin, a member of Inhibitor of Apoptosis Proteins (IAPs), is associated with drug resistance and inhibition of apoptotic mechanisms in numerous hematological malignancies. In the present study, we examined the combined effect of etoposide and siRNA-mediated silencing of survivin on U-937 acute myeloid leukemia cells. The AML cells were transfected with survivin specific siRNA and gene knockdown was confirmed by quantitative real time PCR and western blotting. Subsequently, U-937 cells were assessed for response to etoposide treatment and apoptosis rate was measured with flowcytometery. The cytotoxic effects in siRNA-etoposide group were measured and compared to etoposide single therapy group. Survivin siRNA effectively knocked down the mRNA and protein levels of survivin, which led to lower cell proliferation and enhanced apoptosis. Furthermore, combined treatment of etoposide and survivin siRNA synergistically increased the cell toxic effects of etoposide and its ability to induce apoptosis. PMID- 27262802 TI - Syringic acid protects retinal ganglion cells against H2O2-induced apoptosis through the activation of PI3K/Akt signaling pathway. AB - Oxidative damage is believed to contribute to the pathogenesis of diabetic retinopathy. Syringic acid (SA), a naturally occurring O-methylated trihydroxybenzoic acid monomer extracted from Herba dendrobii, has been shown to possess antioxidant activity. However, the effects of SA on apoptosis of retinal ganglion cells (RGCs) induced oxidative damages have not yet been explored. The present study aimed to detect the effects of SA against hydrogen peroxide (H2O2) induced cell damage in RGCs and to investigate the molecular mechanisms involved in this process. In the present study, we revealed that SA pretreatment obviously inhibited H2O2-induced RGC-5 cell injury. SA pretreatment also decreased H2O2 induced ROS production and MDA content in RGC-5 cells. In addition, SA pretreatment increased Bcl-2 expression and decreased the expression of Bax and cleaved caspase-3 in H2O2-induced RGC-5 cells. Moreover, SA pretreatment obviously increased PI3K and Akt phosphorylation in H2O2-induced RGC-5 cells. In conclusion, our results suggest that SA may protect RGC-5 cells against apoptosis induced by H2O2 through the activation of PI3K/Akt signaling pathway. Thus, SA may be beneficial in the treatment of diabetic retinopathy. PMID- 27262803 TI - Effect of copper sulphate on the antioxidant parameters in the rainbow trout fry, Oncorhynchus mykiss. AB - The aim of this study was to evaluate antioxidant responses of rainbow trout (Oncorhynchus mykiss) exposed to different concentrations of copper sulphate (CuSO4). Fish were exposed to 0 (Group I-control), 5 (Group II), 15 (Group III) and 30 ug/L (Group IV) concentrations of CuSO4 for 14 days. Liver and gills samples were collected at the end of the experiment, and analysed for their oxidant-antioxidant status, including the malondialdehyde (MDA) level, the catalase (CAT) and glutathione peroxidase (GSH-Px) activities as well as the reduced glutathione (GSH) concentration. Results obtained showed that the levels of MDA increased in tissues of fish. Compared to control, GSH level and GSH-Px and CAT activities were significantly reduced in the fish that were exposed to different concentrations of CuSO4. The result demonstrated that CuSO4 has an oxidative-stress-inducing potential in fish. PMID- 27262804 TI - Hydrogen inhibits cytotrophoblast cells apoptosis in hypertensive disorders complicating pregnancy. AB - Hypertensive disorders complicating pregnancy (HDCP) is one of the most serious medical disorders during pregnancy. Hydrogen is a therapeutic antioxidant and used to treat HDCP effectively. However, the molecular mechanism about the effect of hydrogen on HDCP still remains unclear. In this study, we found ROS content in HDCP group was significantly higher than that in the control and was reduced markedly in the presence of 100MUmol/L hydrogen. IL6, Caspase3, Bax1, P-JAK2, P Stat3 and P-p38 expression was much higher than the control, and was notably decreasedby the application of 100MUmol/L hydrogen. Bcl2 expression in HDCP group was notably lower than the control and was increased by 100 MUmol/L hydrogen. The apoptosis rate of cytotrophoblast cells was decreased, andratio of cytotrophoblast cells at G1 and G2 phase was increased and decreased by hydrogen, respectively. All those data indicated a potential molecular mechanism of hydrogen-mediated treatment in HDCP. PMID- 27262805 TI - Induction of linalool as a pharmaceutical and medicinal metabolite via cell suspension culture of cumin (Cuminum cyminum L.). AB - Cumin is an important medicinal plant in Iran. Plant cell suspension culture is a method for the production of medicinal and secondary metabolites. The linalool is a plant secondary metabolite that has been recognized as a neuroprotective agent. The purpose of this study was to evaluate the effects of salicylic acid elicitor on induction of linalool in cell suspension culture of cumin. For this purpose, the cumin seeds were prepared, to obtain sterile seedling, were disinfected with sodium hypochlorite and alcohol, and were cultured on MS basal medium. This research was conducted in two separate experiments including callus induction and suspension cultures. Leaf explants were prepared from sterile seedlings and used to produce callus on MS medium supplemented with 1 mg/l NAA and 0.5 mg/l BAP. In order to establish suspension culture, the appropriate calli were transferred to liquid medium. Then cell cultures were treated with elicitors. The effects of elicitor on the production of linalool secondary metabolite and cell viability were assessed by GC-Mass and tetrazolium test respectively. For this purpose, the salicylic acid (at concentrations of 0, 1, 2, 4 and 8 mg/l) was used. The experimental design was a completely randomized design with five treatments and three replications. The results of cell culture and GC-Mass analysis showed that salicylic acid had significant effects on the linalool production (<0.01). At all concentrations of salicylic acid, viability of the cells in suspension culture experiments was lower than control. Increasing the elicitor concentrations lead to reduction in cell survival. In conclusion it is possible to produce linalool as a secondary metabolite and pharmaceutical agent in cell culture of cumin. It is necessary to determine the best combination of medium and elicitor. PMID- 27262806 TI - Usnea cornuta Korb. and Usnea glabrescens (Vainio) Vainio sens. Lat.: Species to be protected in the peninsula of Edough (Algeria). AB - In the Mediterranean region, Edough Peninsula (Algerian Northeast) has a significant procession of rare plant species biogeographical interest. This communication is based on specimens collected by the author during the realization of a lichen herbarium when her attention was attracted by the striking presence of a fruticose lichen of Usnea genus, on a hawthorn at the entrance of a private neglected garden. One of the harvested species proved to be after identification, Usnea glabrescens (Vainio) Vainio sens. Lat. A second species was harvested meanwhile a few meters away, on a cork oak and identified as Usnea cornuta Korber species ever recorded in Algeria before. PMID- 27262807 TI - The capacity of some newly bacteria and fungi for biodegradation of herbicide trifluralin under agiated culture media. AB - Bioremediation is the use of microorganisms to degrade environmental contaminants (pesticides, polyaromatic hydrocarbons etc.) into less toxic forms or compounds. In this study microbial biodegradation of trifluralin was performed in liquid media with 11 different types of identified fungi and bacteria cultures and their mixtures in agiated culture media. The isolated fungi and bacteria mixtures showed the highest degradation, reaching 93% in the chemical oxygen demand (COD) parameter in four days and 82% as trifluralin active ingredient in five days. Bacteria and fungi mixtures achieved 69% and 66% degradations of trifluralin active ingredient respectively. In the fungi studies, the best removal was achieved by M.Chlamydosporia at 80%, in the bacteria studies, the best removal was achieved by Bacillus simplex about 95% in five days. These different removal rates were due to the microbial differencies. PMID- 27262808 TI - Inhibitory activity on type 2 diabetes and hypertension key-enzymes, and antioxidant capacity of Veronica persica phenolic-rich extracts. AB - Veronica genus (Plantaginaceae) is broadly distributed in different habitats. In this study, the inhibitory activity of free soluble and conjugated phenolic extracts of Veronica persica on key enzymes associated to type 2 diabetes (alpha glucosidase and alpha-amylase) and hypertension (angiotensin I converting enzyme, ACE) was assessed, as well as their antioxidant power. Our results showed that both the extracts inhibited alpha-amylase, alpha-glucosidase and ACE in a dose dependent manner. In particular, free phenolic extract significantly (P<0.05) inhibited alpha-glucosidase (IC50 532.97 ug/mL), whereas conjugated phenolic extract significantly (P<0.05) inhibited alpha-amylase (IC50 489.73 ug/mL) and ACE (290.06 ug/mL). The enzyme inhibitory activities of the extracts were not associated with their phenolic content. Anyway, the inhibition of alpha-amylase, alpha-glucosidase and ACE, along with the antioxidant capacity of the phenolic rich extracts, could represent a putative mechanism through which V. persica exerts its antidiabetes and antihypertension effects. PMID- 27262809 TI - Raf-kinase inhibitor protein attenuates microglia inflammation in an in vitro model of intracerebral hemorrhage. AB - Microglia mediated neuroinflammation plays a crucial role in intracerebral hemorrhage (ICH). Raf kinase inhibitor protein (RKIP), a member of the phosphatidylethanolamine-binding protein (PEBP) family, is a negative regulator of inflammatory responses. However, the expression and anti-inflammatory effects of RKIP in microglia after ICH have not been reported. Therefore, in the current study, we investigated the effects of RKIP on inflammatory responses in erythrocyte lysate-treated BV2 microglia. Furthermore, we analyzed the detailed molecular mechanisms underlying the anti-inflammatory effects of RKIP in microglia. Our results showed that the expression level of RKIP was significantly decreased by erythrocyte lysate treatment in BV2 microglia. Overexpression of RKIP inhibited the production of pro-inflammatory molecules. In addition, overexpression of RKIP attenuated neuronal cell death induced by activated microglia. Moreover, RKIP suppressed the activation of NF-kappaB signaling pathway in erythrocyte lysis-treated BV2 cells. In conclusion, these data suggest that overexpression of RKIP attenuated microglia inflammation through inhibiting the NF-kappaB signaling pathway in erythrocyte lysis-treated BV2 cells. The present study provides evidence that RKIP may be used as an effective molecular target for the treatment of ICH. PMID- 27262810 TI - Efficiency of some soil bacteria for chemical oxygen demand reduction of synthetic chlorsulfuron solutions under agiated culture conditions. AB - This study searches the efficiency of certain soil bacteria on chemical oxygen demand (COD) reduction of synthetic chlorsulfuron solutions under agitated culture conditions. It also aims to determine the turbidity of liquid culture medium with chlorsulfuron during bacterial incubation for 120 hours. As a result the highest and lowest COD removal efficiency of bacteria was determined for Bacillus simplex as 94% and for Micrococcus luteus as 70%, respectively at the end of the 96th hour. It was found that COD removal efficiency showed certain differences depend on the bacterial species. It was also observed that B. simplex had the highest COD removal efficiency and it was a suitable bacterium species for bioremediation of a chlorsulfuron contaminated soils. PMID- 27262811 TI - Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line. AB - Nigella sativa is also known for its properties as a traditional herbal healing for many ailments. In this study, the anticancer properties of thyomquinone (TQ), the active ingredient of N. sativa, were studied using ovarian cancer cell line (Caov-3 cells). The anti-proliferative activity of TQ was determined using MTT and the apoptosis was investigated using Flowcytometry and Annexin-V Assays. Multiparameteric cytotoxicity bioassays were used to quantify the changes in cell permeability and mitochondrial membrane potential. Reactive oxygen species (ROS) and apoptosis-involved cell markers were examined to verify cell death mechanism. The MTT-assay showed that TQ induces anti-proliferative activity on Caov-3 with an IC50 of 6.0+/-0.03 MUg/mL, without any cytotoxic activity towards WRL-68 normal hepatocytes. A significant induction of early phase of apoptosis was shown by annexin-V analysis. Treatment of Caov-3 cells with TQ induces decreases in plasma membrane permeability and mitochondrial membrane potential. Visible decrease in the nuclear area was also observed. A significant decrease is observed in Bcl-2 while Bax is down-regulated. TQ-triggered ROS-mediated has found to be associated with Hsp70 dysregulation, an indicator of oxidative injury. We found that TQ induced anti-cancer effect involves intrinsic pathway of apoptosis and cellular oxidative stress. Our results considered collectively indicated that thyomquinone may be a potential agent for ovarian cancer drug development. PMID- 27262812 TI - Human amniotic fluid derived mesenchymal stem cells cause an anti-cancer effect on breast cancer cell line in vitro. AB - Human amniotic fluid stem cells (hAFSCs) have the ability to self-renew, and multipotent differentiation into three germ layer cells. We obtained 5 ml amniotic fluid from ten 16-20 week pregnant women undergoing amniocentesis. hAFSCs were isolated from all samples, co-cultured with T47D breast cancer cell line and characterized using flow cytometry and RT-PCR. After 3, 4 and 5 days, T47D and HSFCs viability were evaluated with MTT assay. After 5 days of co culture T47D cells viability were decreased. Our findings showed that hAFSCs can release soluble factors in cell culture, causing an efficient anticancer effect. PMID- 27262813 TI - Knockdown of eIF3a attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-beta1. AB - Activation of hepatic stellate cells (HSCs) plays an important role in the development of liver fibrosis. The eukaryotic translation initiation factor (eIF) 3a is the largest subunit of the eIF3 complex and has been involved in pulmonary fibrosis. However, the role of eIF3a in liver fibrosis remains largely unknown. Therefore, in this study, we investigated the role of eIF3a in transforming growth factor-beta1 (TGF-beta1)-induced HSC activation. Our results demonstrated that the expression of eIF3a was up-regulated in human liver fibrotic tissues and activated HSCs. In addition, knockdown of eIF3a suppressed TGF-beta-induced HSC proliferation and the expression of alpha-smooth muscle actin (alpha-SMA) and collagen I. Furthermore, knockdown of eIF3a inhibited the expression of p-Smad3 induced by TGF-beta1 in HSCs. These results suggest that eIF3a may function as a novel regulator to modulate HSC activation, potentially through inhibiting the TGF-beta1/Smad3 signaling pathway. PMID- 27262814 TI - The effect of Morus alba leaves extract and powder on resistin levels and liver transaminase enzymes activities in diabetes. AB - The current study was designed to investigate the changes of the resistin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels of diabetic rats after treatment with Morus alba leaves flavonoid extract (MLE) and Morus alba leaves powder (MLP). Thirty male wistar rats in five groups including control and diabetic groups were included. Diabetic groups consisted of diabetic control, sham and treated group with MLE and MLP. Type 2 diabetes was induced in rats by administration of streptozotocin (STZ) and - nicotinamide. The serum concentrations of resistin and insulin in the study groups were identified by ELISA. ALT and AST activities were assayed by spectrophotometer. For the first time, it was shown that the uptake of MLE and MLP by diabetic rats could significantly decrease the serum fasting blood sugar (FBS), resistin levels and enzymes activity of ALT and AST and increases the concentration of serum insulin significantly (P<0.05). in comparison with the sham group and diabetic control. The results showed that there was no significant difference between the anti diabetic and inflammatory properties of MLE and MLP. In this study, the possible protective effect of MLE and MLP administration was evaluated against destructive effect of STZ on liver and pancreas function in diabetic rats. The results showed that these effects may play an important role in the regulating of adipokines secretion such as resistin and insulin secretion which are involved in the control of diabetes and obesity. MLE and MLP treatment could be useful agents in combination with other therapies in diabetes improvement. PMID- 27262815 TI - PFKFB3 potentially contributes to paclitaxel resistance in breast cancer cells through TLR4 activation by stimulating lactate production. AB - Paclitaxel is a commonly used agent for breast cancer therapy, which comes across the obstacle "drug resistance", resulting in shortened overall survival of patients. Warburg effect has become one character of cancer cell and was reported to induce paclitaxel resistance, the mechanism of which is poorly understood. In this study, we sought to examine the role of 6-Phosphofructo-2-kinase (PFKFB3), a critical regulator of glycolysis, in paclitaxel resistance development. Two clones of paclitaxel resistant breast cancer cells, MCF-7RA and MCF-7RB, were established by a long term exposure of MCF-7 cells to paclitaxel. Consequently, PFKFB3 expression was found to be increased in MCF-7RA and MCF-7RB cells compared with MCF-7 cells. Silencing PFKFB3 expression markedly reduced the IC50 concentrations of MCF-7RA and MCF-7RB cells. Moreover, PFKFB3 modulated toll like receptor 4 (TLR4) and MyD88 expression as well as interleukin (IL)-6 and IL-8 release from breast cancer cells in response to paclitaxel exposure. In addition, PFKFB3 overexpression boosted up fructose-2,6-bisphosphate (F2,6BP) and lactate production. The enhanced lactate contributed to TLR4 signaling activation, IL-6 and IL-8 generation, and cell viability promotion in MCF-7 cells. In all, we characterized the novel role of PFKFB3 in induction of paclitaxel resistance by raising lactate production and activating TLR4 signaling. PMID- 27262816 TI - Basal cell skin cancer and the risk of second primary cancers: a cancer registry based study in Lithuania. AB - PURPOSE: The aim of this population-based cohort study was to determine the risk of second primary cancer in basal cell carcinoma (BCC) patients in Lithuania. METHODS: This analysis was based on patients diagnosed with BCC in Lithuania between 1998 and 2007 and followed until 2011. Standardized incidence ratios for subsequent cancers as a ratio of observed number of cancer cases in people with previous BCC diagnosis to the expected number of cancer cases in the underlying general population were calculated. RESULTS: After diagnosis of BCC, 1442 new cases of selected cancers were diagnosed. Compared with the general population, the incidence of all new primaries combined after BCC was very close to expected. Statistically meaningful increase in developing subsequent cancer was obtained for Hodgkin's lymphoma, prostate cancer, and leukemia in men, and for cancers of the lip, lung, and breast in women. Risk of melanoma and thyroid cancer was significantly elevated in both sexes. Relative risk of cancer of the eye was increased although not significant. CONCLUSIONS: In our study, we found increased cancer risk for cancers related to sun exposure. In addition, increased risks were identified for Hodgkin's lymphoma, thyroid cancer, leukemia, prostate, and breast cancer in BCC patients. PMID- 27262817 TI - Pregnancy loss history at first parity and selected adverse pregnancy outcomes. AB - PURPOSE: To evaluate the association between pregnancy loss history and adverse pregnancy outcomes. METHODS: Pregnancy history was captured during a computer assisted personal interview for 21,277 women surveyed in the National Survey of Family Growth (1995-2013). History of pregnancy loss (<20 weeks) at first parity was categorized in three ways: number of losses, maximum gestational age of loss(es), and recency of last pregnancy loss. We estimated risk ratios for a composite measure of selected adverse pregnancy outcomes (preterm, stillbirth, or low birthweight) at first parity and in any future pregnancy, separately, using predicted margins from adjusted logistic regression models. RESULTS: At first parity, compared with having no loss, having 3+ previous pregnancy losses (adjusted risk ratio (aRR) = 1.66 [95% CI = 1.13, 2.43]), a maximum gestational age of loss(es) at >=10 weeks (aRR = 1.28 [1.04, 1.56]) or having experienced a loss 24+ months ago (aRR = 1.36 [1.10, 1.68]) were associated with increased risks of adverse pregnancy outcomes. For future pregnancies, only having a history of 3+ previous pregnancy losses at first parity was associated with increased risks (aRR = 1.97 [1.08, 3.60]). CONCLUSION: Number, gestational age, and recency of pregnancy loss at first parity were associated with adverse pregnancy outcomes in U.S. women. PMID- 27262819 TI - Epidemiology of measles in vaccinated people, Spain 2003-2014. AB - INTRODUCTION: During the final phase of measles elimination rigorous investigation of each individual case becomes fundamental to confirm or discard cases, particularly among vaccinated people, since they experience a milder disease, and laboratory diagnosis is more complex. Our study focused in the epidemiology of measles in vaccinated people. METHODS: Longitudinal study on measles cases in two dose vaccinated people in Spain from 2003 to 2014. RESULTS: We confirmed 138 measles cases (90 of them, laboratory confirmed) in people with two doses of vaccine. The median of time from last vaccination to rash onset showed a lineal trend (P<.001), in parallel with the number of doses of vaccine received (0, 1, 2 doses). Among confirmed cases, the hospitalization risk decreased inversely proportional to the number of administered vaccine doses (linear trend, P<.001). Only in 23.9% of confirmed cases and 50% of discarded cases the guidelines about sample taking were fulfilled. 50% of samples in two dose vaccinated people were taken without fulfilling time delay criteria. 16.7% (36/215) of discarded cases with a negative IgM result did correspond to samples taken early (first 72h after rash) and could represent false negatives. CONCLUSION: Our results highlight the importance of fulfilling properly the guidelines for laboratory diagnosis in order to confirm or discard every measles case, especially in two dose vaccinated people. When a negative IgM result is obtained in early samples a new IgM test should be practiced, as well as a PCR test, in order to avoid infra-detection of cases. PMID- 27262818 TI - Astrocytic and microglial nicotinic acetylcholine receptors: an overlooked issue in Alzheimer's disease. AB - It is increasingly recognized that astrocytes and microglia-associated dysfunction contribute to AD pathology. In addition, glial nicotinic acetylcholine receptors (nAChRs) play a role in AD-related phenomena, such as neuron survival, synaptic plasticity, and memory. From mechanistic point of view, the glial regulation of pro-inflammatory cytokines, as common contributors in AD, is modulated by nAChRs. Astrocytic and microglial nAChRs contribute to Abeta metabolism, including Abeta phagocytosis and degradation as well as Abeta-related oxidative stress and neurotoxicity. These receptors are also involved in neurotransmission and gliotransmission through indirect interaction with N-Methyl D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptors as well as gamma-aminobutyric acid (GABA) and intracellular calcium regulation. In addition, glial nAChRs participate in trophic factors induced neuroprotection. This review gathers the most recent advances along with the previous data on astrocytic and microglial nAChRs role in AD pathogenesis. PMID- 27262820 TI - Development of a Certified Reference Material for myeloperoxidase-anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA). AB - A serum Certified Reference Material (CRM) for supporting reliable autoimmune diagnostics was recently released by the Institute for Reference Materials and Measurements (IRMM) of the Joint Research Centre of the European Commission. It was produced in collaboration with a Working Group on the Harmonisation of Autoimmune Tests of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC WG-HAT). This material is aimed at facilitating the standardisation of measurements of anti-myeloperoxidase immunoglobulin G antibodies. The CRM could be used as a common calibrant by clinicians and manufacturers thereby significantly improving the comparability of results from commercial immunoassays used for IgG anti-MPO measurements. This paper provides information on the new CRM and its intended use. PMID- 27262821 TI - The VCS parameters: Potential hematological indicators for predicting antituberculosis drug-induced neutropenia. AB - BACKGROUND: The morphological changes in activated neutrophils associated with antituberculosis drugs can be measured by volume, conductivity, and scatter (VCS) technology on the Coulter LH750 hematology analyzer. We conducted the current study to further validate the clinical usefulness of the neutrophil VCS parameters in predicting drug-induced neutropenia. METHODS: Peripheral blood samples were collected from 52 patients with drug-induced neutropenia, 309 patients without any abnormal CBC, and 237 healthy controls. The mean neutrophil volume (MNV) with its distribution width (NDW) and the mean neutrophil scatter (MNS) were studied. RESULTS: We observed a significant increase in the MNV and NDW as well as a significant decrease in the MNS in neutropenia patients approximately one week prior to development of neutropenia compared to healthy controls as well as to case controls. In addition, the delta MNV and delta MNS were respectively correlated well with delta absolute neutrophil counts when neutropenia occurred. The ROC curve analyses showed that the MNV,NDW and MNS had larger areas under curves compared to conventional parameters. With a cutoff of 150.15 for the MNV, a sensitivity of 84.4% and specificity of 75.7% were achieved prior to neutropenia. CONCLUSION: The neutrophil VCS parameters may be clinically useful as potential hematological indicators for predicting antituberculosis drug induced neutropenia. PMID- 27262822 TI - Pretreatment C-reactive protein was an independent prognostic factor for patients with diffuse large B-cell lymphoma treated with RCHOP. AB - BACKGROUND: We assessed the prognostic significance of pretreatment C-reactive protein (CRP) concentration in diffuse large B-cell lymphoma (DLBCL) patients. METHODS: We retrospectively reviewed 156 patients with newly diagnosed DLBCL. Receiver operating characteristic (ROC) curve analysis was used to generate a cutoff value for CRP. Both log-rank test and multivariable analysis by Cox regression model were used to assess the impact of pretreatment CRP concentrations on the overall survival (OS) and progression-free survival (PFS). RESULTS: Among those 156 patients enrolled, increased CRP concentration was seen in 51 patients before treatment (>=20mg/l), while the other 105 patients were considered with low CRP concentration. There was no obvious difference in the baseline characteristics between two groups. Increased CRP concentration was significantly associated with poorer OS and PFS than those patients with low CRP concentration (P=0.001 and P=0.000, respectively). Multivariable analysis further showed that CRP concentration was an independent predictor of OS (hazard ratio [HR]=0.47; 95% confidence interval [CI]=0.24-0.92, P=0.028) and PFS (HR=0.37; 95% CI=0.30-0.87, P=0.013). CONCLUSION: CRP concentration before treatment was an independent prognostic factor in patients with DLBCL. PMID- 27262823 TI - A simplified assay for the quantification of circulating activated protein C. AB - Available assays for circulating levels of activated protein C (APC) are either time-consuming or difficult to use in a routine laboratory, or have a detection limit above normal levels. We have developed a simplified assay that measures both the in vivo free APC and the in vivo APC complexed to PC inhibitor (PCI). We measured APC levels, with both assays, in 339 plasma samples, 165 from patients with venous thromboembolism (VTE) and 174 from healthy individuals. The mean APC level in the 339 samples was 0.038+/-0.010 nM, using a previous assay that measures only the in vivo APC level, and 0.041+/-0.010 nM with the present new assay. The coefficient of correlation between assays was r=0.954 (P<0.001). The mean APC level in VTE patients was 0.034+/-0.009 nM (previous assay) and 0.037+/ 0.009 nM (new assay), significantly lower than those in controls (P<0.001). In both groups there was a significant correlation between the levels obtained by the two assays (P<0.001). These results show that both assays are equivalent, and confirm that the APC level is lower in VTE patients than in healthy individuals. Therefore, the new simplified assay, which measures the sum of circulating free APC and APC complexed to PCI, may be used to estimate the level of circulating APC, and will allow its use in routine laboratories. PMID- 27262825 TI - Changing pattern in the clinical presentation of breast cancer in the absence of a screening program over a period of thirty-three years in Iran. AB - OBJECTIVE: To survey the proportion of stages at the presentation of the disease without a screening program, among a population of breast cancer patients that is as a representative sample of the country in a distinct period. MATERIALS AND METHODS: The population of the current study is found among the female breast cancer patients who were referred to oncology centers in northeastern Iran over a thirty-three-year period from 1980 to 2012. RESULTS: Four thousand patients were divided into three time periods consisting of 521 cases from 1980 to 1990, 1178 cases from 1991 to 2001, and 2302 cases from 2002 to 2012. While there was no difference in the proportions of T1 and T3 tumors, T2 tumors showed an increase (P = 0.001) and T4 tumors a decrease (P = 0.000) during these periods. There was no change in the proportion of stage I, however the proportion of stage II had risen (P = 0.000), while that of stage III (P = 0.002), and stage IV (P = 0.000) had fallen. The study's urban and rural populations experienced a similar trend in this respect, with the exception that the rural population exhibited more striking changes during the study's recent years. CONCLUSION: After a thirty three-year follow up on breast cancer in northeastern Iran, it is obvious that this disease is now presented in its earlier stages even in the absence of a screening program. In spite of this, the proportion of T1 disease and those tumors are discovered by a screening program has not significantly changed. PMID- 27262824 TI - Effect of VKORC1, CYP2C9, CFP4F2, and GGCX Gene Polymorphisms on Warfarin Dose in Japanese Pediatric Patients. AB - BACKGROUND: Warfarin dosage requirements show considerable inter-individual variability. There are some reports of warfarin dose regimens correlating with single nucleotide polymorphisms (SNP) for CYP2C9, VKORC1 and other genes in adults. In children, however, reports are scarcer than in adults and the number of genes examined is more limited. We explored the effects of genetic variation on warfarin dose requirement in Japanese pediatric patients. METHODS: A total of 45 patients who were prescribed warfarin at the Yokohama City University Hospital were included in this study. The influence of genetic polymorphisms on stable warfarin dosage requirement was investigated by genotyping SNPs of the VKORC1, CYP2C9, CYP4F2, and GGCX genes (rs9923231, rs1057910, rs2108622, and rs699664, respectively) in each patient. RESULTS: Patients with the TT genotype in rs9923231 in VKORC1 required significantly lower maintenance dosages than those with the TC genotype (p = 0.001). Multiple regression analysis showed that, while VKORC1 status and patient height account for 78.2 % of the variability in maintenance warfarin dosage, genetic polymorphisms in VKORC1 account for 27 %, although polymorphisms in CYP4F2 and GGCX had no effect on dosage and the effect of CYP2C9 could not be evaluated. CONCLUSIONS: Polymorphisms in VKORC1 partially affected daily warfarin dosage requirements. VKORC1 genotype and height are the primary determinants influencing warfarin dosage in Japanese pediatric patients. Further studies with larger sample sizes are needed to confirm our results. PMID- 27262827 TI - Excess of (236)U in the northwest Mediterranean Sea. AB - In this work, we present first (236)U results in the northwestern Mediterranean. (236)U is studied in a seawater column sampled at DYFAMED (Dynamics of Atmospheric Fluxes in the Mediterranean Sea) station (Ligurian Sea, 43 degrees 25'N, 07 degrees 52'E). The obtained (236)U/(238)U atom ratios in the dissolved phase, ranging from about 2*10(-9) at 100m depth to about 1.5*10(-9) at 2350m depth, indicate that anthropogenic (236)U dominates the whole seawater column. The corresponding deep-water column inventory (12.6ng/m(2) or 32.1*10(12) atoms/m(2)) exceeds by a factor of 2.5 the expected one for global fallout at similar latitudes (5ng/m(2) or 13*10(12) atoms/m(2)), evidencing the influence of local or regional (236)U sources in the western Mediterranean basin. On the other hand, the input of (236)U associated to Saharan dust outbreaks is evaluated. An additional (236)U annual deposition of about 0.2pg/m(2) based on the study of atmospheric particles collected in Monaco during different Saharan dust intrusions is estimated. The obtained results in the corresponding suspended solids collected at DYFAMED station indicate that about 64% of that (236)U stays in solution in seawater. Overall, this source accounts for about 0.1% of the (236)U inventory excess observed at DYFAMED station. The influence of the so called Chernobyl fallout and the radioactive effluents produced by the different nuclear installations allocated to the Mediterranean basin, might explain the inventory gap, however, further studies are necessary to come to a conclusion about its origin. PMID- 27262826 TI - Fatigue, anxiety and depression overrule the role of oncological treatment in predicting self-reported health complaints in women with breast cancer compared to healthy controls. AB - BACKGROUND: Women with breast cancer often attribute their health problems as side effects caused by oncological treatments. The aim of the study was to examine and compare self-reported health complaints (SHC) in postmenopausal patients with breast cancer to healthy controls. METHOD: Women with breast cancer (N = 196) filled in 5 questionnaires 1-2 years after surgery; SHC Inventory, Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), Fatigue - Functional Assessment of Cancer Therapy-Fatigue subscale (FACIT-F), Fatigue Visual Analog Scale (Fatigue VAS), and Hospital Anxiety and Depression Scale (HADS). Controls comprised 101 blood donors who reported on the questionnaires except for HADS. Bonferroni adjustment and p < 0.0017 was considered statistically significant for SHC Inventory, p < 0.05 for the remaining questionnaires. RESULTS: The patients, mean age 58.0 (SD 9.5), reported significantly more self-reported health complaints, whereof 6 of 29 complaints were significantly elevated compared to the controls, mean age 57.0 (SD 5.8) (p < 0.001). HADS scores in patients fell into normal range, mean 6.3 (SD 5.7). A subgroup of 48 patients experienced more frequent and severe symptoms in all the questionnaires compared to the remaining 148 patients, and the 101 controls. Among the patients, fatigue, anxiety and depression explained 49% of the total variance in self-reported health complaints (p <= 0.001). CONCLUSION: Most women with breast cancer (76%) reported health complaints equal to the healthy controls. Fatigue, anxiety and depression, not oncological treatments, were significant predictors for the complaints. PMID- 27262828 TI - MRI-based estimation of liver function by intravoxel incoherent motion diffusion weighted imaging. AB - PURPOSE: To explore the usefulness of intravoxel incoherent motion (IVIM) to evaluate the hepatic functional reserve as expressed by the model for Child-Pugh class. MATERIALS AND METHODS: IVIM diffusion-weighted imaging (DWI) using 10 different b values were performed on a Philips 3.0T MR scanner in 70 patients with liver cirrhosis and 60 healthy volunteers as the control group. Patients with liver cirrhosis were subdivided into three groups: Child-Pugh class A: 29 cases; Child-Pugh class B: 19 cases; Child-Pugh class C: 22 cases. Pure molecular diffusion (D), pseudo-diffusion (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated, and used to determine liver function, as indicated by the Child-Pugh class. RESULTS: The ICC values of D, D*, f and ADC between two radiologists were 0.997, 0.986, 0.985 and 0.995, respectively. D*, f and ADC values of liver cirrhosis group were significantly lower than control group (P<0.001, P=0.016, P=0.042, respectively). D*, f and ADC values significantly decreased with increasing Child-Pugh scores (p<0.05). Child Pugh scores were inversely correlated with D* and f values (r=-0.423, r=-0.620, respectively). The areas under the curve (AUCs) of D* and f for evaluating liver function were 0.67-0.90 and 0.78-0.89, respectively. CONCLUSION: IVIM DWI may be a useful image-based method for assessing liver function. PMID- 27262829 TI - Vectorial total generalized variation for accelerated multi-channel multi contrast MRI. AB - PURPOSE: To develop and implement an efficient reconstruction technique to improve accelerated multi-channel multi-contrast MRI. THEORY AND METHODS: The vectorial total generalized variation (TGV) operator is used as a regularizer for the sensitivity encoding (SENSE) technique to improve image quality of multi channel multi-contrast MRI. The alternating direction method of multipliers (ADMM) is used to efficiently reconstruct the data. The performance of the proposed method (MC-TGV-SENSE) is assessed on two healthy volunteers at several acceleration factors. RESULTS: As demonstrated on the in vivo results, MC-TGV SENSE had the lowest root-mean-square error (RMSE), highest structural similarity index, and best visual quality at all acceleration factors, compared to other methods under consideration. MC-TGV-SENSE yielded up to 17.3% relative RMSE reduction compared to the widely used total variation regularized SENSE. Furthermore, we observed that the reconstruction time of MC-TGV-SENSE is reduced by approximately a factor of two with comparable RMSEs by using the proposed ADMM based algorithm as opposed to the more commonly used Chambolle-Pock primal-dual algorithm for the TGV-based reconstruction. CONCLUSION: MC-TGV-SENSE is a better alternative than the existing reconstruction methods for accelerated multi channel multi-contrast MRI. The proposed method exploits shared information among the images (MC), mitigates staircasing artifacts (TGV), and uses the encoding power of multiple receiver coils (SENSE). PMID- 27262830 TI - Radiologic adjacent segment degeneration 2 years after lumbar fusion for degenerative spondylolisthesis. AB - INTRODUCTION: Lumbar fusion is now a currently accepted treatment for degenerative lumbar spondylolisthesis (DLSP), but may induce adjacent segment degeneration (ASD). The present study hypothesis was that there are radiological parameters associated with ASD. The study objective was to determine predictive factors of ASD. MATERIAL AND METHODS: A single-center retrospective study included patients operated on between 2006 and 2013 for DLSP. Radiological parameters were analyzed on preoperative, immediate postoperative and final follow-up lateral X-ray. ASD was defined by the following adjacent segment criteria:>3mm anteroposterior translation,>10 degrees segmental kyphosis, or>50% loss of disc height. RESULTS: One hundred and seven patients were included: 79% female; mean age, 67+/-10.2 years. Fusion involved 1 level in 67% of cases and 2 or more in 33%, with transforaminal lumbar interbody fusion (TLIF) in 27% of cases. There was overall significant gain in lumbar lordosis (mean, 3.1 degrees ; P=0.04). At a mean 27.8 months' follow-up, 29% of cases showed ASD and 10% required surgical reintervention. Preoperative anterior imbalance and long fusion (>2 levels) were significantly associated with ASD (OR=2.81, 95% CI [1.17-6.74] versus OR=2.76, 95% CI [1.15-6.63]). There were no significant differences according to postoperative radiological parameters, or to TLIF (OR=1.8, 95% CI [0.7-4.4]). CONCLUSION: Twenty-nine percent of patients developed ASD, with a surgical revision rate of 10%. ASD risk factors comprised high number of instrumented levels and preoperative sagittal imbalance. LEVEL OF EVIDENCE: IV, retrospective cohort. PMID- 27262831 TI - Congenital dislocation of the knee at birth - Part 2: Impact of a new classification on treatment strategies, results and prognostic factors. AB - INTRODUCTION: An original classification of congenital dislocation of the knee (CDK) was drawn up, based on neonatal semiology. The objective of the present study was to assess impact on treatment decision-making and prognosis. MATERIAL AND METHODS: Fifty-one CDKs in 40 patients were classified neonatally into 3 types: I, reducible (n=28); II, recalcitrant (n=16); and III, irreducible (n=7). Number of anterior skin grooves, range of motion (RoM), flexion deficit and reduction stability were recorded. Depending on reducibility, treatment comprised: physiotherapy with splints, traction with cast immobilization, or surgery. At follow-up, knees were assessed in terms of RoM and stability. RESULTS: Mean age at first consultation was 5.6 days (range: 0-30). Mean age at follow-up was 9 years (range: 1-26). Physiotherapy with splinting achieved stable reduction in all type-I knees. Five type-II knees (31%) required traction, none of which needed surgery. Four type-III knees (57%) required surgery. Outcome was good or excellent in 82% of type-I knees, good in 68% of type II and poor in all type-III knees. CONCLUSION: The study confirmed the relevance of the present neonatal classification to treatment, with increasing rates of surgical indication and decreasing rates of satisfactory outcome from types I to III. Therapeutic attitude can be graded according to severity of CDK. LEVEL OF EVIDENCE: IV, single-center retrospective series. PMID- 27262832 TI - Iron Deficiency without Anemia: A Common Yet Under-Recognized Diagnosis in Young Women with Heavy Menstrual Bleeding. AB - STUDY OBJECTIVE: To assess the proportion of iron deficiency that is not detected with a screening hemoglobin or complete blood count (CBC) alone in young women with heavy menstrual bleeding. DESIGN: Retrospective review of electronic medical records. SETTING: Nationwide Children's Hospital in Columbus, Ohio. PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: One hundred fourteen young women aged 9 19 years consecutively referred to a young women's hematology clinic with a complaint of heavy menstrual bleeding. RESULTS: Fifty-eight (50.9%) of all patients had ferritin <20 ng/mL indicating iron deficiency. Of the 58 patients with iron deficiency, only 24 (41.4%) were anemic and 25 (46.3%) were microcytic. The sensitivity of hemoglobin alone and CBC alone for identifying women with ferritin <20 ng/mL was 41.4% (95% confidence interval [CI], 28.7-54.1) and 46.3% (95% CI, 33.0-59.6), respectively. Both tests had reasonable specificity at 91.1% (95% CI, 83.6-98.5) for hemoglobin and 83.9% for CBC (95% CI, 74.3-93.6). Patients had significantly higher odds of having iron deficiency if they were overweight or obese (odds ratio, 2.81; 95% CI, 1.25-6.29) compared with patients with normal body mass index. Age at presentation for heavy menstrual bleeding, presence of an underlying bleeding disorder, and median household income were not significantly associated with iron deficiency. CONCLUSION: In adolescents with heavy menstrual bleeding, fewer than half of iron deficiency cases are detected when screening is performed with hemoglobin or blood count alone. Measuring ferritin levels in at-risk patients might allow for earlier implementation of iron therapy and improvement in symptoms. PMID- 27262833 TI - Health-Related Quality of Life in Adolescents and Young Adults with Polycystic Ovary Syndrome: A Systematic Review. AB - STUDY OBJECTIVE: To review recent data exploring the relationship between polycystic ovary syndrome (PCOS) and health-related quality of life (HRQoL) in adolescents and its implication for management of adolescents with this syndrome. DESIGN AND SETTING: We performed a systematic literature search in MedLine, Embase and PsychInfo from 1980 to September 2015 and manual search in reference lists of selected articles. Inclusion criteria were articles in English or French with a focus on HRQoL in patients with PCOS aged between 13 and 24 years. Qualitative, cross-sectional, or interventional studies were considered as eligible. Two reviewers each independently selected and reviewed the relevant articles. RESULTS: Of a total of 93 publications, 7 were selected through a systematic search, and 2 were added after a manual search. Seven studies used quantitative methods and 2 studies used a qualitative one. A meta-analysis was not possible because of the methodological diversity among the selected articles. All articles showed that PCOS has a negative influence on HRQoL in adolescents. Body weight issues and body mass index (BMI) appeared to have the strongest effect on HRQoL; some studies reported a normalization of HRQoL scores after adjustment for BMI. Patient information and patient-provider relationship were also reported to affect HRQoL. Elements in favor of the effectiveness of multidisciplinary management, associated lifestyle modifications, and psychological support, in improving HRQoL were identified. CONCLUSION: PCOS significantly reduces HRQoL in adolescent girls. The extent to which body weight issues and BMI mediate this effect deserves further evaluation. A detailed understanding of the psychosocial challenges that patients with PCOS face is limited, mainly because of the small number of studies available, restricted sample size, and the methodological diversity of the questionnaires used. The effect of early lifestyle modification, and medical and psychological treatment should continue to be explored. PMID- 27262834 TI - Laparoscopic Treatment of Mixed Malignant Ovarian Germ Cell Tumor in a 16-Year Old Female Adolescent. AB - BACKGROUND: Malignant ovarian germ cell tumors are rare entities, although they account for a large proportion of ovarian masses in young women. These tumors have traditionally been removed via laparotomy, because of their large size and solid nature. The use of laparoscopy for treatment of adnexal masses in adolescents has been heavily debated and poorly studied to date. CASE: A 16-year old female patient presented with abdominal pain and an 11-cm adnexal mass on ultrasound. An emergent laparoscopic salpingo-oophorectomy was performed without complication. Pathology revealed a mixed malignant ovarian germ cell tumor. SUMMARY AND CONCLUSION: Laparoscopic fertility-sparing surgery offers many benefits over laparotomy, and should be considered in cases of young women with large adnexal masses, even if potential for malignancy exists. PMID- 27262835 TI - Adolescent Deliveries in a Secondary-Level Care Hospital of Cameroon: A Retrospective Analysis of the Prevalence, 6-Year Trend, and Adverse Outcomes. AB - STUDY OBJECTIVE: Adolescents are generally ill-equipped to deal with the burden of a pregnancy. A high prevalence of adolescent pregnancies is among the indicators of limitations toward the achievement of the Millennium Development Goals in most developing countries. We sought to determine the prevalence, 6-year trend, and adverse outcomes of adolescent deliveries. We also tested whether being married decreased the risk of adverse fetal outcomes in these adolescents. DESIGN: A 6-year retrospective register analysis. SETTING: Buea Regional Hospital. PARTICIPANTS: Birth records from 2007 to 2012. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prevalence and 6-year trend in the rate of adolescent deliveries; adverse fetal outcomes. RESULTS: The overall prevalence of adolescent deliveries was 9.9% (491 of 4941). There was no significant change in the annual prevalence of adolescent deliveries over 6 years (P trend = .8). Adolescent pregnancies were at higher risk of preterm deliveries (deliveries at gestational age <37 completed weeks; odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3 2.2; P < .01), low birth weight (defined as birth weight <2600 g; OR, 1.8; 95% CI, 1.4-2.3; P < .01), and neonatal asphyxia (OR, 1.4; 95% CI, 1.1-1.7; P < .01). There was no significant difference in the frequency of adverse outcomes between married and single adolescents. CONCLUSION: One of every 10 babies is born from adolescent mothers in the Buea Regional Hospital. Whether these mothers are married or not, their neonates are exposed to higher morbidity. This emphasizes the need for more adolescent-friendly public health policies geared toward reducing the prevalence of this condition to improve the chances of attaining the Millennium Development Goals in Cameroon. PMID- 27262836 TI - Laparoscopic Myomectomy of a Symptomatic Uterine Leiomyoma in a 15-Year-Old Adolescent. AB - BACKGROUND: Although adnexal masses and ovarian torsion are common causes of acute pain in the female adolescent, fibroids are an uncommon etiology and little is reported in the literature. Because of the rarity of adolescent leiomyomas, the best surgical management is still unknown. CASE: To our knowledge, this is the first case report of a laparoscopic myomectomy in the adolescent population. The removed fibroid is one of the largest documented cases of uterine leiomyoma in adolescents. SUMMARY AND CONCLUSION: Degenerative fibroids, albeit less common, should be kept on the differential diagnosis, as a possible cause of pelvic mass and pain in the adolescent population. Fibroids in the adolescent patient, like the adult, can be managed with minimally invasive surgery with excellent clinical outcomes. PMID- 27262837 TI - Cytotoxicity mechanism of alpha-MMC in normal liver cells through LRP1 mediated endocytosis and JNK activation. AB - Alpha-momorcharin (alpha-MMC), a type I ribosome-inactivating protein isolated from Momordica charantia, is a potential drug candidate with strong anti-tumor activity. However, alpha-MMC has a severe hepatotoxicity when applied in vivo, which may greatly hinders its use in clinic in the future. The biological mechanism of hepatotoxicity induced by alpha-MMC is largely unknown, especially the mechanism by which alpha-MMC enters the hepatocytes. In this study, we investigated alpha-MMC-induced cytotoxicity in normal liver L02 cell line as well as the mechanism underlying it. As expected, alpha-MMC is more toxic in L02 cells than in various normal cells from other organs. The cytotoxic effect of alpha-MMC on L02 cells is found to be mediated through cell apoptosis as detected by flow cytometry and fluorescence microscopy. Importantly, alpha-MMC was shown to bind to a specific receptor on cell membrane, as the density of the cell membrane receptor is closely related to both the amount of alpha-MMC endocytosed and the cytotoxicity in different cell lines. By using LRP1 competitive inhibitor alpha2 M or siRNA targeting LRP1, we further identified that LRP1 protein served as the membrane receptor for alpha-MMC. Both alpha2-M and siRNA targeting LRP1 can significantly inhibit alpha-MMC's endocytosis as well as its cytotoxicity in L02 cells. In addition, it was found that alpha-MMC can activate the JNK signalling pathways via LRP1 in L02 cells. As JNK activation often leads to cell apoptosis, the activation of JNK may play an important role in alpha-MMC-induced cytotoxicity. To our knowledge, this is the first report showing that LRP1 mediates the cytotoxicity of alpha-MMC through (1) endocytosis and induced apoptosis and (2) the activation of the JNK pathway. Our findings shed light on the fundamental mechanism of hepatotoxicity of alpha-MMC and offer reference to understand its mechanism of lymphocytotoxicity and neurotoxicity. PMID- 27262838 TI - Is it the egg or the endometrium? Elevated progesterone on day of trigger is not associated with embryo ploidy nor decreased success rates in subsequent embryo transfer cycles. AB - PURPOSE: The purpose of our study was to determine if progesterone (P4) values on day of trigger affect certain cycle outcome parameters, ploidy status of embryos, as well as pregnancy outcomes in the subsequent first frozen embryo transfer cycle. METHODS: Two hundred thirty-eight patients undergoing pre-gestational screening and freeze all protocol at our fertility center from 2013 to 2014 were included. Excluded patients were those whom had cancelled cycles prior to egg retrieval as well as cycles utilizing donor eggs. Once patients were identified as eligible for this study, frozen serum from the day of trigger was identified and analyzed using the Siemens Immulite 2000. Number of eggs retrieved, number of available embryos for biopsy, and number of euploid/aneuploid embryos were analyzed. The first frozen embryo transfer cycle was linked to the initial egg retrieval and outcomes including pregnancy rates, and live birth/ongoing pregnancy rates were calculated and analyzed. A discriminatory P4 value of 1.5 ng/ml was set. Group A had P4 values of less than 1.5 ng/ml and group B had P4 values greater than or equal to 1.5 ng/ml. T tests and chi-squared tests were used for statistical analysis. RESULTS: Group A had an average trigger P4 value of 0.87 +/- 0.3 and group B had an average trigger P4 of 2.1 +/- 0.8. Table 1 shows the baseline characteristics of both group A and group B. The only significant difference between the two groups was total gonadotropin dosage (IU) with a p value of 0.02 and estradiol (pg/ml) at trigger, also with a p value of 0.02 (Table 1). Number of eggs retrieved, number of embryos biopsied, number euploid/aneuploid, and non-diagnosis embryos were all non-significant. Chi-square analysis was used to compare pregnancy rates between the two groups after the first frozen embryo transfer cycle. Group A had a pregnancy rate of 72 % and Group B had a pregnancy rate of 66.7 %, which was not significant. Ongoing pregnancy/live birth rates were 65.6 % in group A and 66.67 % in group B, also not significant (Table 2). CONCLUSIONS: P4 values on day of trigger do not affect number of eggs retrieved and number of chromosomally normal embryos available for transfer in a subsequent embryo transfer cycle. Elevated P4 values (>=1.5 ng/ml) also do not affect pregnancy rates or live birth/ongoing pregnancy rates in the first subsequent frozen embryo transfer cycle. PMID- 27262839 TI - Serum hCG-beta levels of postovulatory day 12 and 14 with the sequential application of hCG-beta fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle. AB - PURPOSE: To investigate hCG-beta level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. METHODS: A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-beta levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-beta levels and the degree of hCG-beta increase from POD 12 to 14 were determined for each pregnancy outcome. RESULTS: POD 12 and 14 hCG-beta levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-beta levels of POD 12 and 14 and the fold increase of hCG-beta levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-beta had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-beta levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-beta levels >=30.2 mIU/mL, the cutoff level of increase of hCG-beta for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-beta and fold increase of hCG-beta improved predictability of pregnancy outcome as compared with that of POD 12 hCG-beta alone. The cutoff values of POD 12 and 14 serum hCG-beta levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-beta level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-beta level >=31.5 mIU/mL, the cutoff value for fold increase of hCG-beta was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-beta level and fold increase of hCG beta significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. CONCLUSIONS: Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies. PMID- 27262840 TI - Health-related quality of life in older people with osteoporotic vertebral fractures: a systematic review and meta-analysis. AB - Health-related quality of life in osteoporotic patients with vertebral fracture is of increasing interest, but relevant studies have yielded debatable results. This systematic review and meta-analysis of 16 observational studies demonstrate a clear association between physical health status and presence of vertebral fracture after accounting for age. This meta-analysis was conducted to identify if there are any differences between physical and/or mental health-related quality of life (HRQoL) in older people with osteoporosis based on conventional T score definitions and the presence or absence of vertebral fracture. A comprehensive search was undertaken using the databases of PubMed, Embase, Medline, Web of Science, and the "grey" literature from 1950 to the end of April 2015. Search terms for vertebral fracture (VF) included VF, osteoporotic fracture, fragility fracture, and spinal fracture. Quality of life was searched using the following terms: quality of life, health-related quality of life, HRQoL, and QoL. Strict inclusion and exclusion criteria were used. The standardized mean difference (SMD) was calculated for each HRQoL domain by the difference in means between case and control groups divided by the pooled SD of participants. Sixteen eligible studies were identified involving 3131 men and women. There was evidence of publication bias and heterogeneity. The meta analysis showed worse physical (SMD = 0.53, 95 % confidence interval (CI) 0.38 to 0.68; P < 0.001) and mental (SMD = 0.19, 95 % CI 0.05 to 0.33; P = 0.009) HRQoL in osteoporotic older people with vertebral fracture compared to those without fracture. Similar differences were observed for physical HRQoL in further analyses accounting for possible confounding effects of age. Sub-analysis to assess associations between number/severity of fractures and time since fracture was not possible due to small numbers of studies that accounted for age. Osteoporotic older people with vertebral fracture have worse physical HRQoL than osteoporotic older people without vertebral fracture, even after accounting for age differences. PMID- 27262841 TI - High density lipoprotein subfractions and paraoxonase 1 in children. AB - The Lipoprint system (Quantimetrix Corp., CA, USA), enables the determination of 10 high density lipoprotein (HDL) subfractions in contrast to the 5 HDL subfractions that can be determined by ultracentrifuge analysis. HDL subfractions, and their relationships to the arylesterase (PON1-A) and lactonase (PON1-L) activities of paraoxonase 1 (PON1), together with total-, very low density lipoprotein- and low density lipoprotein (LDL)-cholesterol and LDL subfractions were investigated in the serum of 27 mildly hypercholesterolemic children and 21 healthy controls. Our results suggest the antiatherogenity of large HDL (L-HDL) subfractions and the atherogenity of small HDL (S-HDL) subfractions in the study groups. However, the relationship between the intermediate HDL (I-HDL) subfractions with the LDL subfractions and other lipoproteins did not suggest that I-HDL subfractions are antiatherogenic. No significant association between PON1-A and the HDL subfractions was found. In contrast, PON1-L activity positively correlated with the antiatherogenic large HDL1 subfraction and negatively with intermediate HDL subfractions 4, 5 and 6. Our results contribute to the knowledge of the roles of total HDL and ten individual HDL subfractions in children and adolescents. PMID- 27262842 TI - Hepatokines and non-alcoholic fatty liver disease. AB - Nowadays non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver pathology both in adults and children. NAFLD manifestation ranges from a simple liver steatosis to steatohepatitis (nonalcoholic steatohepatitis - NASH), which may progress to advanced fibrosis, cirrhosis and end-stage liver disease. Due to the coexistence of visceral obesity, insulin resistance and dyslipidemia, NAFLD is considered to be the hepatic manifestation of metabolic syndrome. In recent years, in the pathogenesis of metabolic syndrome, type 2 diabetes mellitus, cardiovascular disease and also NAFLD, more and more attention has been paid to the so-called organokines, proteins with both paracrine or/and endocrine activities. These include most known adipokines (mainly produced by adipose tissue), myokines (mainly produced by skeletal muscles) and hepatokines exclusively or predominantly produced by the liver. It was shown that the liver may affect the lipids and glucose metabolism by hepatokines released into the blood and NAFLD seems to be associated with altered hepatokines production. Fetuin-A, fibroblast growth factor-21 (FGF-21), selenoprotein P, sex hormone binding globulin (SHBG), angiopoietin-related growth factor (also known as angiopoietin-related protein 6) and leukocyte derived chemotaxin 2 (LECT2) are considered as the most important hepatokines. In this review, we provide an overview of the main hepatokines and we summarize the association of liver derived proteins with the development and progression of NAFLD. PMID- 27262843 TI - Osteopontin-stimulated apoptosis in cardiac myocytes involves oxidative stress and mitochondrial death pathway: role of a pro-apoptotic protein BIK. AB - Increased osteopontin (OPN) expression in the heart, specifically in myocytes, associates with increased myocyte apoptosis and myocardial dysfunction. Recently, we provided evidence that OPN interacts with CD44 receptor, and induces myocyte apoptosis via the involvement of endoplasmic reticulum stress and mitochondrial death pathways. Here we tested the hypothesis that OPN induces oxidative stress in myocytes and the heart via the involvement of mitochondria and NADPH oxidase-4 (NOX-4). Treatment of adult rat ventricular myocytes (ARVMs) with OPN (20 nM) increased oxidative stress as analyzed by protein carbonylation, and intracellular reactive oxygen species (ROS) levels as analyzed by ROS detection kit and dichlorohydrofluorescein diacetate staining. Pretreatment with NAC (antioxidant), apocynin (NOX inhibitor), MnTBAP (superoxide dismutase mimetic), and mitochondrial KATP channel blockers (glibenclamide and 5-hydroxydecanoate) decreased OPN-stimulated ROS production, cytosolic cytochrome c levels, and apoptosis. OPN increased NOX-4 expression, while decreasing SOD-2 expression. OPN decreased mitochondrial membrane potential as measured by JC-1 staining, and induced mitochondrial abnormalities including swelling and reorganization of cristae as observed using transmission electron microscopy. OPN increased expression of BIK, a pro-apoptotic protein involved in reorganization of mitochondrial cristae. Expression of dominant-negative BIK decreased OPN stimulated apoptosis. In vivo, OPN expression in cardiac myocyte-specific manner associated with increased protein carbonylation, and expression of NOX-4 and BIK. Thus, OPN induces oxidative stress via the involvement of mitochondria and NOX-4. It may affect mitochondrial morphology and integrity, at least in part, via the involvement of BIK. PMID- 27262844 TI - Natural History of Patients Presenting with Autoimmune Hepatitis and Coincident Nonalcoholic Fatty Liver Disease. AB - BACKGROUND: Given the increase of nonalcoholic fatty liver disease (NAFLD) in the general population, a similar rise might be expected in autoimmune hepatitis (AIH) patients. AIMS: We sought to determine the clinical outcome of patients with coincident AIH and NAFLD. METHODS: We identified all intradepartmental AIH cases, and those meeting study criteria were placed into one of three cohorts: AIH only, AIH and simple steatosis (SS), and AIH and nonalcoholic steatohepatitis (NASH). The following outcome and clinical data were analyzed: incidence of all cause mortality, incidence of liver-related mortality, incidence of liver-related adverse outcomes, and prevalence of cirrhosis at index biopsy. RESULTS: Out of a total 73 study patients, 14 % classified as AIH with SS and 16 % as AIH and NASH. Fifty percent of AIH and NASH patients had cirrhosis at index biopsy as compared to 18 % of AIH-only patients (p = 0.032). Patients with AIH and NASH had a relative risk of 7.65 (95 % CI 1.43-40.8) for liver-related mortality and 2.55 (95 % CI 0.92-7.09) for liver-related adverse outcomes, as compared to the AIH only cohort. No significant difference in outcome measures existed in comparing (AIH only) with (AIH and SS) cohorts. DISCUSSION: Patients with coincident AIH and NASH were more likely to present with cirrhosis and more likely to develop adverse clinical outcome with decreased survival as compared to AIH-only patients. These findings suggest that simultaneous exposure confers a clinically significant increased risk, which may warrant closer follow-up and surveillance. PMID- 27262846 TI - Regulation of CD40 signaling in colon cancer cells and its implications in clinical tissues. AB - CD40 is a member of the tumor necrosis factor receptor family. We reveal here a correlation between CD40 expression and colon cancer differentiation. Upon CD40 ligand (CD40L) binding, CD40/CD40L signaling inhibited colon cancer proliferation, induced apoptosis, stalled cells at G0/G1, and influenced cell adhesion and metastasis. Clustering analysis identified the elevation of aryl hydrocarbon receptor repressor (AHRR) expression along with activation of CD40/CD40L signaling. Examination of clinical specimens revealed that both AHR and AHRR levels correlated with colon cancer histological grade. In addition, high expression of AHRR was associated with high expression of CD40 in tumor cells, with CD40L expression being particularly high in the tumor interstitium. Real-time PCR and western blotting analysis showed that AHRR expression in colon cancer cells was up-regulated by CD40L binding. The likely mediating signaling pathways for the effects of CD40 are described herein. PMID- 27262845 TI - Aspirin-induced heat stress resistance in chicken myocardial cells can be suppressed by BAPTA-AM in vitro. AB - Our recent studies have displayed the protective functions of aspirin against heat stress (HS) in chicken myocardial cells, and it may be associated with heat shock proteins (HSPs). In this study, we further investigated the potential role of HSPs in the aspirin-induced heat stress resistance. Four of the most important HSPs including HspB1 (Hsp27), Hsp60, Hsp70, and Hsp90 were induced by aspirin pretreatment and were suppressed by BAPTA-AM. When HSPs were induced by aspirin, much slighter HS injury was detected. But more serious damages were observed when HSPs were suppressed by BAPTA-AM than those cells exposed to HS without BAPTA-AM, even the myocardial cells have been treated with aspirin in prior. Comparing to other HSPs, HspB1 presented the largest increase after aspirin treatments, 86 fold higher than the baseline (the level before HS). These findings suggested that multiple HSPs participated in aspirin's anti-heat stress function but HspB1 may contribute the most. Interestingly, during the experiments, we also found that apoptosis rate as well as the oxidative stress indicators (T-SOD and MDA) was not consistently responding to heat stress injury as expected. By selecting from a series of candidates, myocardial cell damage-related enzymes (CK-MB and LDH), cytopathological tests, and necrosis rate (measured by flow cytometry assays) are believed to be reliable indicators to evaluate heat stress injury in chicken's myocardial cells and they will be used in our further investigations. PMID- 27262847 TI - Effects and biological limitations of +Gz acceleration on the autonomic functions related circulation in rats. AB - The effects of gravitational loading (G load) on humans have been studied ever since the early 20th century. After the dangers of G load in the vertical head-to leg direction (+Gz load) became evident, many animal experiments were performed between 1920 and 1945 in an effort to identify the origins of high G-force induced loss of consciousness (G-LOC), which led to development of the anti-G suit. The establishment of norms and training for G-LOC prevention resulted in a gradual decline in reports of animal experiments on G load, a decline that steepened with the establishment of anti-G techniques in humans, such as special breathing methods and skeletal muscle contraction, called an anti-G straining maneuver, which are voluntary physiological functions. Because the issue involves humans during flight, the effects on humans themselves are clearly of great importance, but ethical considerations largely preclude any research on the human body that probes to any depth the endogenous physiological states and functions. The decline in reports on animal experiments may therefore signify a general decline in research into the changes seen in the various involuntary, autonomic functions. The declining number of related reports on investigations of physiological autonomic systems other than the circulatory system seems to bear this out. In this review, we therefore describe our findings on the effects of G load on the autonomic nervous system, cardiac function, cerebral blood flow, tissue oxygen level, and other physiological autonomic functions as measured in animal experiments, including denervation or pharmacological blocking, in an effort to present the limits and the mechanisms of G-load response extending physiologically. We demonstrate previously unrecognized risks due to G load, and also describe fundamental research aimed at countering these effects and development of a scientific training measure devised for actively enhancing +Gz tolerance in involuntary, autonomic system functions. The research described here is rough and incomplete, but it is offered as a beginning, in the hope that researchers may find it of reference and carry the effort toward completion. The advances described here include (1) a finding that cerebral arterial perfusion pressure decreases to nearly zero under +5.0 Gz loads, (2) indications that G load may cause myocardial microinjuries, (3) detection of differences between cerebral regions in tissue-oxygen level under +3.0 Gz load, (4) discovery that hypotension is deeper under decreasing +Gz loads than increasing +Gz loads with use of an anti-G system, due in part to suppression of baroreceptor reflex, and (5) revelations and efforts investigating new measures to reduce cerebral hypotension, namely the "teeth-clenching pressor response" and preconditioning with slight but repeated G loads. PMID- 27262849 TI - A propensity score-matched comparison of surgical precision obtained by using volumetric analysis between robot-assisted laparoscopic and open partial nephrectomy for T1 renal cell carcinoma: a retrospective non-randomized observational study of initial outcomes. AB - PURPOSE: We compared surgical outcomes between robot-assisted laparoscopic partial nephrectomy (RAPN) and open partial nephrectomy (OPN) by using volumetric analysis in a propensity score-matched analysis. METHODS: We analyzed the records of 279 patients with normal contralateral kidneys who underwent RAPN or OPN for T1 renal tumors between 2012 and 2014. Volumetric studies to assess the vascularized parenchymal volume of the operated kidney were performed 2 months preoperatively and 6 months postoperatively. Patient data, including age, body mass index, presence of hypertension and/or diabetes mellitus, American Society of Anesthesiologists score, tumor size, preoperative estimated glomerular filtration rate, and tumor complexity using the renal nephrometry score, were matched 1:1 using propensity score matching between groups. RESULTS: This cohort included 100 patients who underwent RAPN and 179 who underwent OPN. After matching, 48 patients were included in each group. Mean tumor diameter was 31 mm, and about 14 % were high-complexity tumors (RENAL score 10-12). The RAPN and OPN groups showed no significant differences in the rate of preservation of global renal function (95 vs. 92 %) and parenchymal volume of the operated kidney (84 vs. 79 %). Similarly, urological complications did not significantly differ between groups. Surgical margins were negative in all tumors. Patients who underwent RAPN had lower estimated blood loss (p < 0.0001) and shorter postoperative length of hospital stay (p < 0.0001) than those who underwent OPN. CONCLUSION: RAPN can offer acceptable surgical outcomes and precision, compared to OPN, with decreased estimated blood loss and hospital stay. PMID- 27262848 TI - The role of biofilm on orthopaedic implants: the "Holy Grail" of post-traumatic infection management? AB - The development of post-traumatic infection is potentially a limb threatening condition. The orthopaedic trauma literature lags behind the research performed by our arthroplasty colleagues on the topic of implant-related infections. Surgical site infections in the setting of a recent ORIF are notoriously hard to eradicate due to biofilm formation around the implant. This bacteria-friendly, dynamic, living pluri-organism structure has the ability to morph and adapt to virtually any environment with the aim to maintain the causative organism alive. The challenges are twofold: establishing an accurate diagnosis with speciation/sensitivity and eradicating the infection. Multiple strategies have been researched to improve diagnostic accuracy, to prevent biofilm formation on orthopaedic implants, to mobilize/detach or weaken the biofilm or to target specifically bacteria embedded in the biofilm. The purpose of our paper is to review the patho-physiology of this mysterious pluri-cellular structure and to summarize some of the most pertinent research performed to improve diagnostic and treatment strategies in biofilm-related infections. PMID- 27262850 TI - Ultrasound induces contraction of the bladder smooth muscle. AB - PURPOSE: To investigate whether the treatment of overt postpartum urinary retention (PUR) with low-intensity pulsed ultrasound (LIPUS) was clinically effective and whether LIPUS could accelerate bladder smooth muscle (BSM) contraction by opening the L-type calcium channels and activating the Ca(2+) signaling pathway. METHODS: Records of 136 patients undergoing PUR were retrospectively reviewed in two different groups for LIPUS and neostigmine between from 2014 to July 2015. The rats BSM strips in vitro were irradiated by LIPUS. The contraction frequency and amplitude were recorded with BL-410F biological experimental system. The BSM cells were constructed and identified by alpha-actin-specific antibody staining, and the intracellular Ca(2+) concentration was analyzed by flow cytometry. RESULTS: The clinical trial indicated that LIPUS had potential therapeutic effect on PUR (80.6 vs. 64.1 %, p < 0.05), and the BSM strip contractility was increased by LIPUS (p < 0.001), and the concentration of Ca(2+) was markedly enhanced by about twofold than that without LIPUS exposure (p < 0.01). Besides, nimodipine could suppress the contraction of BSM and the concentration of intracellular Ca(2+) which was caused by ultrasound. CONCLUSIONS: The results suggested LIPUS had potential therapeutic effect on PUR and the Ca(2+) signaling pathway was involved in the mechanism. The ultrasound irradiation may provide a new method for PUR therapy. PMID- 27262851 TI - Relationship of serum levels and dietary intake of isoflavone, and the novel bacterium Slackia sp. strain NATTS with the risk of prostate cancer: a case control study among Japanese men. AB - PURPOSE: Isoflavones may play a role in the prevention of hormone-related cancers. Equol is an isoflavone metabolized from daidzein in the presence of certain intestinal bacteria. Slackia sp. strain NATTS, a newly identified equol producing bacterium, was recently isolated from human feces in Japan. We investigated the association of serum levels and dietary intake of isoflavones and Slackia sp. strain NATTS with the risk of prostate cancer in a case-control study among Japanese men. METHODS: Fifty-six patients with newly diagnosed prostate cancer and 56 hospital controls were enrolled in this study. Isoflavones were assessed by measurement of serum levels and administration of a food frequency questionnaire. Slackia sp. strain NATTS in feces was also measured. The odds ratios (ORs) and 95 % confidence intervals (CIs) for prostate cancer were then determined using a logistic regression model. RESULTS: The adjusted ORs for prostate cancer in comparison with the highest to lowest categories were 0.06 (95 % CI 0.02-0.24) for serum genistein, 0.18 (95 % CI 0.06-0.52) for daidzein, 0.16 (95 % CI 0.06-0.46) for glycitein, 0.52 (95 % CI 0.22-1.22) for equol, 0.86 (95 % CI 0.30-2.48) for dietary genistein, and 0.80 (95 % CI 0.28-2.28) for dietary daidzein. The adjusted OR for prostate cancer in comparison with values above versus below the median was 0.95 (95 % CI 0.42-2.16) for Slackia sp. strain NATTS. CONCLUSION: Our study findings suggest that high serum levels of genistein, daidzein, and glycitein are significantly associated with a decreased risk of prostate cancer among Japanese men. PMID- 27262853 TI - Nelumbo Nucifera leaf protects against UVB-induced wrinkle formation and loss of subcutaneous fat through suppression of MCP3, IL-6 and IL-8 expression. AB - Nelumbo nucifera has long been used in traditional medicine in East Asian countries such as China and Korea. In this study, we report the different property of several Nelumbo nucifera leaf (NNL) extracts on adipocyte differentiation. Adipogenesis was stimulated by administration of dichloromethyl (DCM) or n-hexan extract of NNL but attenuated by that of water extract. We also show that topical administration of DCM extract of NNL attenuated ultraviolet-B (UVB)-mediated wrinkle formation and reduction of subcutaneous (SC) fat in vivo. Interestingly, UVB-induced blood contents of triglyceride (TG) were attenuated significantly by topical administration of the DCM extract. In addition, we found that UVB-induced expression of cytokines (interleukin-6; IL-6, interleukin-8; IL 8, and monocyte chemotactic protein-3; MCP3), which were reported as regulators in SC fat metabolism, was attenuated in mouse skin fibroblast cells upon administration of the DCM extract. Collectively, our data suggest that topical administration of DCM extract of NNL, which plays a regulatory role in adipogenesis, could attenuate UVB-induced wrinkle formation and the metabolism of blood lipids by regulating the expression of cytokines such as IL-6, IL-8, and MCP3 in skin fibroblast cells. Our findings support further development of DCM extract of NNL as a potential therapeutic agent for prevention of photoaging related disorders. PMID- 27262852 TI - Molecular characterization of Staphylococcus aureus isolates causing skin and soft tissue infections in patients from Malakand, Pakistan. AB - Comparatively few studies have been published describing Staphylococcus aureus/MRSA epidemiology in Central Asia including Pakistan. Here, we report the genotyping of Staphylococcus aureus strains (that include both methicillin susceptible and methicillin-resistant Staphylococcus aureus) from community- and hospital-acquired skin and soft-tissue infections in a tertiary care hospital in the Malakand district of the Khyber Pakhtunkhwa Province of Pakistan. Forty-five isolates of Staphylococcus aureus were characterized by microarray hybridization. Twenty isolates (44 %) were MRSA, whereas 22 (49 %) were PVL-positive. Fourteen isolates (31 %) harboured both mecA and PVL genes. The dominant clones were CC121 MSSA (n = 15, 33 %) and the PVL-positive "Bengal Bay Clone" (ST772-MRSA-V; n = 13, 29 %). The PVL-positive CC8-MRSA-IV strain "USA300" was found once. The pandemic ST239-MRSA-III strain was absent, although it has previously been observed in Pakistan. These observations require a re-assessment of schemes for initial antibiotic therapy to cover MRSA and they emphasise the need for a rapid and non-molecular test for PVL. PMID- 27262854 TI - Preparation and characterization of zinc and copper co-doped WO3 nanoparticles: Application in photocatalysis and photobiology. AB - In this study, pure, Zn, Cu, Zn,Cu co-doped WO3 nanoparticles samples were prepared by precipitation and co-precipitation methods. These nanoparticles were characterized by field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), energy dispersive X-ray spectrometer (EDX), Dynamic light scattering (DLS), UV-visible and photoluminescence (PL) spectroscopy. The synthesized pure, Zn, Cu, Zn,Cu co-doped WO3 nanoparticles have smart optical properties and average sizes with 3.2, 3.12, 3.08 and 2.97eV of band-gap, 18.1, 23.2, 25.7 and 30.2nm, respectively. Photocatalytic activity of four nanoparticles was studying towards degradation of gentamicin antibiotic under ultraviolet and visible light irradiation. The result showed that Zn,Cu co-doped WO3 possessed high photocatalytic activity. The photocatalytic activity of WO3 nanoparticles could be remarkably increased by doping the Zn and Cu impurity. This can be attributed to the fact that the red shift of absorption edge and the trapping effect of the mono and co-doped WO3 nanoparticles. The research result presents a general and effective way to prepare different photocatalysts with enhanced visible and UV light-driven photocatalytic performance. Antibacterial activity of four different WO3 nanoparticles against Escherichia coli bacterium has been assessed by the agar disc method under light irradiation and dark medium. It is concluded from the present findings that WO3 nanoparticles can be used as an efficient antibacterial agent. PMID- 27262855 TI - Value Based Care and Patient-Centered Care: Divergent or Complementary? AB - Two distinct but overlapping care philosophies have emerged in cancer care: patient-centered care (PCC) and value-based care (VBC). Value in healthcare has been defined as the quality of care (measured typically by healthcare outcomes) modified by cost. In this conception of value, patient-centeredness is one important but not necessarily dominant quality measure. In contrast, PCC includes multiple domains of patient-centeredness and places the patient and family central to all decisions and evaluations of quality. The alignment of PCC and VBC is complicated by several tensions, including a relative lack of patient experience and preference measures, and conceptions of cost that are payer focused instead of patient-focused. Several strategies may help to align these two philosophies, including the use of patient-reported outcomes in clinical trials and value determinations, and the purposeful integration of patient preference in clinical decisions and guidelines. Innovative models of care, including accountable care organizations and oncology patient-centered medical homes, may also facilitate alignment through improved care coordination and quality-based payment incentives. Ultimately, VBC and PCC will only be aligned if patient-centered outcomes, perspectives, and preferences are explicitly incorporated into the definitions and metrics of quality, cost, and value that will increasingly influence the delivery of cancer care. PMID- 27262856 TI - A multi-institutional survey of interventional radiology for type II endoleaks after endovascular aortic repair: questionnaire results from the Japanese Society of Endoluminal Metallic Stents and Grafts in Japan. AB - PURPOSE: To investigate the current status of interventional radiology (IR) procedures for a type II endoleak (T2EL) in Japan, and to identify the technical aspects that affect treatment results. MATERIALS AND METHODS: A retrospective survey was conducted by distributing questionnaires to 25 institutions. The eligibility criteria were endovascular aortic repair (EVAR) performed using commercial stent grafts and IR performed for T2EL between January 2007 and December 2013. Technical success was defined as disappearance of the EL on digital subtraction angiography immediately after embolization, and imaging success was defined as no EL on contrast-enhanced computed tomography within 6 months. Statistical comparisons of the number of involved branches, embolization level, embolic material, and changes in aneurysm size were made between the imaging success and imaging failure groups. The technical and imaging success rates were also compared between the initial therapy and repeat groups. RESULTS: A total of 166 cases were investigated. Initial therapy was performed in 147 cases (88.6 %), with repeat therapy in 19 cases (11.4 %). Transcatheter arterial embolization (TAE) was used most frequently, in 161 cases (97 %), with direct puncture (DP) used in 5 cases (3 %). Both coil embolization for the branches and NBCA embolization for the sac were frequently chosen. The technical success rate was 83.2 % (TAE group), and the imaging success rate was 46.5 % (TAE + DP groups). Branch + sac embolization was performed more frequently in the imaging success group. There was no significant difference in the number of involved branches or embolic material between the imaging success and imaging failure groups. Enlargement of the aneurysm was more frequently seen in the imaging failure group. There were no significant differences in the technical success and imaging success rates between the initial therapy and repeat groups. CONCLUSION: This is the first report of a multi-institutional questionnaire survey of IR procedures for T2EL after EVAR in Japan that was conducted to determine the current status. Enlargement of aneurysm size after embolization was more frequently seen in the imaging failure group. It is important to embolize both branch and sac to achieve imaging success, regardless of embolic material. Long term outcomes need to be investigated. PMID- 27262857 TI - Persistent truncus arteriosus on dual source CT. AB - Persistent truncus arteriosus is a rare congenital cardiac disease with variable presentation. The exact preoperative diagnosis and delineation of anatomy are very important because the optimal timing and procedure for truncus arteriosus repair are decided on the basis of the morphological characteristics. Moreover, the presence of associated anomalies influences the surgical outcome and mortality in these patients. Dual-source computed tomographic evaluation with three-dimensional post-processing is highly valuable for delineating its precise morphology and to identify and characterize the associated anomalies. Also depiction of the precise aortic arch morphology and simultaneous evaluation of the airway are very useful in treatment planning. This pictorial review provides an overview of the imaging spectrum of truncus arteriosus and various associated anomalies as seen on dual-source computed tomography. PMID- 27262859 TI - Working in the Mirror: Left Atrial Appendage Closure in a Patient With Dextrocardia. PMID- 27262858 TI - INFRAFRONTIER: a European resource for studying the functional basis of human disease. AB - Ageing research and more generally the study of the functional basis of human diseases profit enormously from the large-scale approaches and resources in mouse functional genomics: systematic targeted mutation of the mouse genome, systemic phenotyping in mouse clinics, and the archiving and distribution of the mouse resources in public repositories. INFRAFRONTIER, the European research infrastructure for the development, systemic phenotyping, archiving and distribution of mammalian models, offers access to sustainable mouse resources for biomedical research. INFRAFRONTIER promotes the global sharing of high quality resources and data and thus contributes to data reproducibility and animal welfare. INFRAFRONTIER puts great effort into international standardisation and quality control and into technology development to improve and expand experimental protocols, reduce the use of animals in research and increase the reproducibility of results. In concert with the research community and the International Mouse Phenotyping Consortium (IMPC), INFRAFRONTIER is currently developing new pilot platforms and services for the research on ageing and age-related diseases. PMID- 27262860 TI - Stent Thrombosis With Drug-Eluting Stents and Bioresorbable Scaffolds: Evidence From a Network Meta-Analysis of 147 Trials. AB - OBJECTIVES: This study sought to perform a systematic review and network meta analysis to compare the relative safety and efficacy of contemporary DES and BVS. BACKGROUND: To improve outcomes of patients undergoing percutaneous coronary revascularization, there have been advances in the design of drug-eluting stents (DES), including the development of drug-eluting bioresorbable vascular scaffolds (BVS). METHODS: Prospective, randomized, controlled trials comparing bare-metal stents (BMS), paclitaxel-eluting stents (PES), sirolimus-eluting stents (SES), Endeavor zotarolimus-eluting stents (E-ZES), cobalt-chromium (CoCr) everolimus eluting stents (EES), platinum-chromium (PtCr)-EES, biodegradable polymer (BP) EES, Resolute zotarolimus-eluting stents (R-ZES), BP biolimus-eluting stents (BP BES), hybrid sirolimus-eluting stents (H [Orsiro]-SES), polymer-free sirolimus- and probucol-eluting stents, or BVS were searched in online databases. The primary endpoint was definite or probable stent thrombosis at 1 year. RESULTS: A total of 147 trials including 126,526 patients were analyzed in this study. All contemporary DES were superior to BMS and PES in terms of definite or probable stent thrombosis at 1 year. CoCr-EES, PtCr-EES, and H-SES were associated with significantly lower risk than BVS. CoCr-EES and H-SES were superior to SES and BP BES. The risk of myocardial infarction was significantly lower with H-SES than with BVS. There were no significant differences regarding all-cause or cardiac mortality. Contemporary devices including BVS showed comparably low risks of repeat revascularization. CONCLUSIONS: Contemporary DES, including biocompatible DP-DES, BP-DES, and polymer-free DES, showed a low risk of definite or probable stent thrombosis at 1 year. BVS had an increased risk of device thrombosis compared with CoCr-EES, PtCr-EES, and H-SES. Data from extended follow-up are warranted to confirm the long-term safety of contemporary coronary devices. PMID- 27262862 TI - Imaging Comparisons of Coregistered Native and Stented Coronary Segments by High Definition 60-MHz Intravascular Ultrasound and Optical Coherence Tomography. PMID- 27262861 TI - The Impact of Post-Procedural Asymmetry, Expansion, and Eccentricity of Bioresorbable Everolimus-Eluting Scaffold and Metallic Everolimus-Eluting Stent on Clinical Outcomes in the ABSORB II Trial. AB - OBJECTIVES: The study sought to investigate the relationship between post procedural asymmetry, expansion, and eccentricity indices of metallic everolimus eluting stent (EES) and bioresorbable vascular scaffold (BVS) and their respective impact on clinical events at 1-year follow-up. BACKGROUND: Mechanical properties of a fully BVS are inherently different from those of permanent metallic stent. METHODS: The ABSORB II (A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions) trial compared the BVS and metallic EES in the treatment of a de novo coronary artery stenosis. Protocol mandated intravascular ultrasound imaging was performed pre- and post-procedure in 470 patients (162 metallic EES and 308 BVS). Asymmetry index (AI) was calculated per lesion as: (1 - minimum scaffold/stent diameter/maximum scaffold/stent diameter). Expansion index and optimal scaffold/stent expansion followed the definition of the MUSIC (Multicenter Ultrasound Stenting in Coronaries) study. Eccentricity index (EI) was calculated as the ratio of minimum and maximum scaffold/stent diameter per cross section. The incidence of device oriented composite endpoint (DoCE) was collected. RESULTS: Post-procedure, the metallic EES group was more symmetric and concentric than the BVS group. Only 8.0% of the BVS arm and 20.0% of the metallic EES arm achieved optimal scaffold/stent expansion (p < 0.001). At 1 year, there was no difference in the DoCE between both devices (BVS 5.2% vs. EES 3.1%; p = 0.29). Post-procedural devices asymmetry and eccentricity were related to higher event rates while there was no relevance to the expansion status. Subsequent multivariate analysis identified that post-procedural AI >0.30 is an independent predictor of DoCE (hazard ratio: 3.43; 95% confidence interval: 1.08 to 10.92; p = 0.037). CONCLUSIONS: BVS implantation is more frequently associated with post-procedural asymmetric and eccentric morphology compared to metallic EES. Post-procedural devices asymmetry were independently associated with DoCE following percutaneous coronary intervention. However, this approach should be viewed as hypothesis generating due to low event rates. (ABSORB II Randomized Controlled Trial [ABSORB II]; NCT01425281). PMID- 27262863 TI - Revisiting the Network of Drug-Eluting Stent Trials: Bioresorbable Scaffolds Enter the Arena. PMID- 27262864 TI - Does Asymmetric Expansion of Bioresorbable Vascular Scaffolds Cause Stent Failure? PMID- 27262865 TI - Takotsubo Cardiomyopathy After Transcatheter Aortic Valve Replacement. PMID- 27262866 TI - Integrated 3D Echo-X-Ray Navigation Guided Transcatheter Closure of Complex Multiple Atrial Septal Defects. PMID- 27262867 TI - In Vivo Molecular Imaging of Ruptured Coronary Atherosclerotic Plaque Using IVUS, OCT, and FDG-PET/CT. PMID- 27262868 TI - The Reliability of Oral and Pharyngeal Dimensions Captured with Acoustic Pharyngometry. AB - Acoustic Pharyngometry (APh) is a method for quantifying oropharyngeal tract configuration using sound wave reflection and is commonly used in diagnostics and research of sleep apnea. The standard preset output of APh (minimal cross sectional area) has been established as reliable. However, by conducting post processing measures on specific breathing tasks, APh data can also reveal oral length, oral volume, pharyngeal length, and pharyngeal volume. Given that these measures may have utility in dysphagia research, the reliability of these measures is unknown and is the focus of the current study. Ten young healthy female volunteers completed two sessions of APh data collection to obtain measures of oral length, oral volume, pharyngeal length, and pharyngeal volume 1 week apart. Two-way mixed intraclass correlation coefficients were calculated to establish intra-rater reliability, inter-rater reliability, and test-retest reliability. Results revealed excellent levels of agreement within and across raters for all oropharyngeal tract parameters. Levels of test-retest agreement for oral length and oral volume indicated these parameters are appropriate for monitoring change within an individual. All parameters were deemed to have acceptable test-retest values as outcome measures in group-level analysis. PMID- 27262869 TI - Prevalence of metabolic syndrome in Iran: A 2011 update. AB - BACKGROUND: The aim of the present study was to determine the prevalence of metabolic syndrome and its individual components among the Iranian adult population in 2011 and to investigate changes between 2007 and 2011. METHODS: Data from two rounds of the Surveillance of Risk Factors of Non-communicable Diseases national surveys conducted in 2007 and 2011 were pooled. Metabolic syndrome was defined according to International Diabetes Federation criteria. RESULTS: In 2007, the prevalence of metabolic syndrome among adults aged 25-64 years was 35.95 (95% confidence interval [CI] 34.27-37.63), which decreased to 32.96 (95% CI 30.73-35.18) in 2011 (P = 0.0108). Despite this overall decline, the prevalence of central obesity (P = 0.1383), raised triglycerides (P = 0.3058), and reduced high-density lipoprotein cholesterol (HDL-C; P = 0.5595) remained constant. There was a trend towards a decline in the proportion of individuals with increased blood pressure (P = 0.0978), and the proportion of adults with increased fasting plasma glucose (FPG) increased (P < 0.0001). In 2011, the prevalence of central obesity, raised triglycerides, reduced HDL-C, increased blood pressure and increased FPG was 51.88 (95% CI 48.97-54.79), 36.99 (95% CI 34.52-39.45), 54.72 (95% CI 50.87-58.57), 38.92 (95% CI 36.19-41.64), and 24.97 (95% CI 22.02-27.93) respectively. CONCLUSIONS: Over the period 2007-11, the prevalence of metabolic syndrome has decreased slightly in Iran, although prevalence of increased FPG has increased significantly. One-third of the Iranian adult population is diagnosed with metabolic syndrome. PMID- 27262870 TI - Comparison of enteral ethanol and benzodiazepines for alcohol withdrawal in neurocritical care patients. AB - We designed a study to evaluate the use of benzodiazepines and ethanol in patients being assessed for alcohol withdrawal and compare outcomes between the two agents. This is a retrospective chart review of patients admitted to neurocritical care or neurosurgical services who were at risk for ethanol withdrawal between June 2011 and September 2015. Patients were divided into two groups based on the first medication administered for alcohol withdrawal management, either benzodiazepine (n=50) or enteral ethanol (n=50). The primary endpoint was the maximum change in Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA) score within the first 24hours. Secondary endpoints included maximum and minimum CIWA score in 5days, length of stay, and change in Glasgow Coma Scale. Study groups differed by mortality risk, level of coma at admission, and other clinical characteristics, with the ethanol group appearing less severely ill. There was no significant difference between the two groups in the maximum change in CIWA score at 24hours (-0.97, 95%CI: -3.21 to 1.27, p=0.39). Hospital and intensive care unit length of stay was 6.5 days and 1 day shorter for the ethanol group (p=0.03 and p=0.02, respectively). In summary, enteral ethanol was preferentially used in patients who are more likely to be capable of tolerating oral intake. We found that the change from baseline in CIWA score or other physiologic variables was not substantially different between the two agents. The overall utility of benzodiazepines and enteral ethanol remains unclear for this population and further study is needed to determine superiority. PMID- 27262871 TI - Blood mitochondrial enzymatic assay as a predictor of long-term outcome in severe traumatic brain injury. AB - Recent studies have observed the central role of mitochondrial dysfunction in severe traumatic brain injury (sTBI). One hundred and seven sTBI patients (18 65years old, presenting within 8hours of injury) were randomised for a placebo controlled phase II trial of progesterone with or without hypothermia. We serially analysed blood mitochondrial enzymes (Complex I [C1], Complex IV [C4] and pyruvate dehydrogenase complex [PDH]) using a dipstick assay at admission and 7days later for 37 patients, irrespective of assigned group. Favorable Glasgow Outcome Scale (GOS) at 1year was associated with admission C1 levels above 0.19MUg, admission C4 levels above 0.19MUg and day 7 C1 levels above 0.17MUg, all per 25MUl of blood. Unfavorable GOS at 1year was associated with admission serum PDH levels above 0.23MUg/25MUl of blood. Survivors at 1year had significantly higher admission serum C1 levels above 0.19MUg/25MUl and day 7 C1 levels above 0.17MUg/25MUl. To our knowledge this is the first clinical trial associating blood mitochondrial enzymes with long-term outcome in sTBI. Serial monitoring and optimisation of blood C1, C4 and PDH levels could aid in prognostication and potentially guide in using mitochondrial targeted therapies. Blood mitochondrial enzymatic assay might suggest global reduction-oxidation status. PMID- 27262872 TI - Clinical significance of intra-nodal naevi in sentinel node biopsies for malignant melanoma. AB - BACKGROUND: Intra-nodal naevi (INN) identified during assessment of a sentinel lymph node for melanoma are not an uncommon finding. Little is known about their clinical significance. Patients with INN are treated as sentinel node biopsy (SNB) negative currently. Our aim was to assess the significance of INN in patients who undergo SNB for melanoma. METHODS: 353 melanoma patients who underwent a SNB between November 1999 and June 2012 were retrospectively analysed from a prospectively collected database. The patients were divided into SNB negative, INN, isolated tumour cells (ITC) and SNB positive groups. Outcome measures of nodal recurrence, distal recurrence and survival were used to assess the differences between the groups. RESULTS: 203 patients were SNB negative, 103 were positive of which 13 had ITC, 47 had INN (13%). Overall median follow up was 2.3 years (range 0.1-14.1 years). Our data demonstrated a statistically significant survival benefit for patients who had an INN compared to the SNB positive and ITC group. INN patients also had significantly better nodal and regional recurrence compared to SNB positive patients. There was no difference between INN and SNB negative patients. CONCLUSION: We have clinically demonstrated that patients with INN on SNB can be adequately treated as SNB negative patients. PMID- 27262874 TI - Erratum to: Awareness of Pre-exposure Prophylaxis for HIV, Willingness to Use It and Potential Barriers or Facilitators to Uptake Among Men Who Have Sex with Men in Spain. PMID- 27262873 TI - Effect of Cell Adhesion Molecule 1 Expression on Intracellular Granule Movement in Pancreatic alpha Cells. AB - Although glucagon secreted from pancreatic alpha cells plays a role in increasing glucose concentrations in serum, the mechanism regulating glucagon secretion from alpha cells remains unclear. Cell adhesion molecule 1 (CADM1), identified as an adhesion molecule in alpha cells, has been reported not only to communicate among alpha cells and between nerve fibers, but also to prevent excessive glucagon secretion from alpha cells. Here, we investigated the effect of CADM1 expression on the movement of intracellular secretory granules in alpha cells because the granule transport is an important step in secretion. Spinning disk microscopic analysis showed that granules moved at a mean velocity of 0.236 +/- 0.010 MUm/s in the mouse alpha cell line alphaTC6 that expressed CADM1 endogenously. The mean velocity was significantly decreased in CADM1-knockdown (KD) cells (mean velocity: 0.190 +/- 0.016 MUm/s). The velocity of granule movement decreased greatly in alphaTC6 cells treated with the microtubule-depolymerizing reagent nocodazole, but not in alphaTC6 cells treated with the actin-depolymerizing reagent cytochalasin D. No difference in the mean velocity was observed between alphaTC6 and CADM1-KD cells treated with nocodazole. These results suggest that intracellular granules in pancreatic alpha cells move along the microtubule network, and that CADM1 influences their velocity. PMID- 27262875 TI - HIV Status Communication with Sex Partners and Associated Factors Among High-Risk MSM and Transgender Women in Lima, Peru. AB - Men who have sex with men (MSM) and transgender women (TW) are key populations in the HIV epidemic. HIV status communication between sex partners can inform decisions regarding sexual behavior. MSM and TW were asked about HIV status communication with sex partners at baseline, 9- and 18-months. GEE models assessed associations with HIV status communication at baseline using prevalence ratios (PRs) and longitudinally using odds ratios (ORs). At baseline, those who had previously had an HIV test, disclosed their HIV status to 42 % of their sex partners. HIV status communication was associated with knowing their sex partner's HIV status at baseline (aPR 5.20) and longitudinally (aOR 1.86). HIV positivity at baseline was negatively associated with HIV status communication during follow-up (aOR 0.55). All reported aPRs and aORs have p < 0.05. Interventions promoting HIV status communication and more frequent HIV testing should be explored as current efforts are insufficient. PMID- 27262876 TI - Cytotoxic triterpenoid saponins from Clematis tangutica. AB - Eight previously undescribed oleanane-type triterpenoid saponins, clematangoticosides A-H, together with eight known saponins, were isolated from the whole plants of Clematis tangutica (Maxim.) Korsh. Their structures were elucidated by extensive spectroscopic analysis, in combination with chemical methods (acid hydrolysis and mild alkaline hydrolysis). Clematangoticosides D-G were found to be unusual 23, 28-bidesmosidic glycosides. The cytotoxic activities of all of the isolated saponins were evaluated against the four human cancer cell lines SGC-7901, HepG2, HL-60 and U251MG. Clematoside S, sapindoside B, kalopanax saponin A, and koelreuteria saponin A exhibited cytotoxicity against all of the test cancer cell lines with IC50 values in the range of 1.88-27.20 MUM, while clematangoticoside D and F showed selective cytotoxicity against SGC-7901 with IC50 values of 24.22 and 21.35 MUM, respectively. PMID- 27262877 TI - Natural variability in acyl moieties of sugar esters produced by certain tobacco and other Solanaceae species. AB - A unique feature of glandular trichomes of plants in the botanical family Solanaceae is that they produce sugar esters (SE), chemicals that have been shown to possess insecticidal, antifungal, and antibacterial properties. Sugar esters of tobacco (Nicotiana tabacum) provide pest resistance, and are important flavor precursors in oriental tobacco cultivars. Acyl moieties of SEs in Nicotiana spp., petunia, and tomato are shown to vary with respect to carbon length and isomer structure (2-12 carbon chain length; anteiso-, iso-, and straight-chain). Sugar esters and their acyl groups could serve as a model to explore the basis of phenotypic diversity and adaptation to natural and agricultural environments. However, information on the diversity of acyl composition among species, cultivars, and accessions is lacking. Herein, described is the analysis of SE acyl groups found in 21 accessions of Nicotiana obtusifolia (desert tobacco), six of Nicotiana occidentalis subsp. hesperis, three of Nicotiana alata, two of N. occidentalis, four modern tobacco cultivars, five petunia hybrids, and one accession each of a primitive potato (Solanum berthaultii) and tomato (Solanum pennellii). A total of 20 different acyl groups was observed that were represented differently among cultivars, species, and accessions. In Nicotiana species, acetate and iso- and anteiso-branched acids prevailed. Straight-chain groups (2-8 carbons) were prominent in petunias, while octanoic acid was prominent in N. alata and N. * sanderae. Two unexpected acyl groups, 8-methyl nonanoate and decanoate were found in N. occidentalis subsp. hesperis. Longer chain groups were found in the petunia, tomato, and potato species studied. PMID- 27262878 TI - Protocol for the development of a core outcome set for autologous fat grafting to the breast. AB - INTRODUCTION: One in eight women will develop breast cancer in their lifetime. Reconstruction is routinely offered to patients and can be autologous and/or implant based. One area of growing interest in autologous fat grafting (AFG). Our group recently published a systematic review and meta-analysis of this topic which showed 51 different outcomes were being utilized in the published literature, with substantial heterogeneity in their definitions. METHODS AND ANALYSIS: A Delphi consensus exercise amongst key stakeholders will be conducted using the long list of 51 outcomes generated through our previous work. We will first group these according to the six domains previously identified; oncological, clinical, aesthetic and functional, patient-reported, process and radiological. Through sequential rounds of voting, the long list of outcomes will be narrowed down using predefined rules of agreement. ETHICS AND DISSEMINATION: No patients will be involved in this study and ethical approval is not required. The research will be published in a peer-reviewed journal. It will also be presented at national and international conferences in the fields of plastic, reconstructive and aesthetic surgery as well as breast surgery and at more general surgical and methodological conferences. It will be disseminated electronically and in print. Brief reports of the review findings will be disseminated directly to the appropriate audiences of surgeons and societies through email and other modes of communication. PMID- 27262879 TI - Primary and recurrent sporadic desmoids: Prognostic factors influencing recurrence-free survival after complete gross resection. AB - INTRODUCTION: There is continuing controversy over the significance of prognostic factors in sporadic desmoid-type fibromatosis (DF). Further, only limited data is available in the literature concerning second recurrence in patients with recurrent DF. The purpose of this study was to identify prognostic factors influencing recurrence-free survival (RFS) and to determine rates of local recurrence (LR) in patients with primary and recurrent DF. METHODS: Fifty-three consecutive patients with DF who underwent surgery at a single institution were identified. As a result of strict exclusion criteria, a homogeneous cohort of thirty-two patients who received macroscopically complete resection was included in this study and split into a primary (PG) and recurrent disease (RG) group. Clinicopathological parameters and immunohistochemical markers were retrospectively and independently analyzed in both groups. RESULTS: The local recurrence rate was 35% for the PG and 33% for the RG. The PG's calculated median time to relapse was 17 months, and the RG's was 29 months. The estimated 1-, 5-, and 8-year RFS rates for the PG were 75%, 64%, and 55% while the corresponding RFS rates for the RG were 69%, 69%, and 52%, respectively. In primary disease, extraabdominal tumor location was the only significant adverse prognostic factor associated with worse RFS (p = 0.008). Whereas in recurrent disease, age >=40 yrs (p = 0.022) and R0 margin status (p = 0.049) correlated with a significantly better outcome. CONCLUSION: Recurrence in primary and recurrent DF is characterized by different predictive factors and benefits from distinct therapeutic strategies. Immunohistochemical markers are valuable tools in the diagnosis of DF, although have limited potential in predicting the outcome. PMID- 27262880 TI - Challenging situations in partial nephrectomy. AB - Although most partial nephrectomies are performed as primary procedures in the elective or semi-imperative setting on kidneys with relatively normal anatomy, this is not always the case. The indications for partial nephrectomy continue to expand and it is becoming particularly relevant in patients with single functioning kidneys, poor kidney function, anatomical anomalies and hereditary syndromes predisposing to multiple kidney cancers, such as Von Hippel-Lindau syndrome. These, along with previous abdominal surgery, pose surgical challenges. In this article we offer advice as to how to tackle these unusual situations. An ability to master the whole range of indications will allow the modern upper renal tract surgeon to offer partial nephrectomy to a wider range of patients. PMID- 27262881 TI - Intravenous versus topical tranexamic acid in primary total hip replacement: A systemic review and meta-analysis. AB - OBJECTIVE: Total hip arthroplasty (THA) is associated with substantial blood loss. Tranexamic acid (TXA) could reduce perioperative blood loss. The optimal administration routine of TXA remains controversial. The objective of the present systemic review and meta-analysis was to compare the effectiveness and safety of various application methods of tranexamic acid in primary THA. METHODS: Potential relevant literature was identified from electronic databases including Medline, PubMed, Embase, ScienceDirect, web of science and Cochrane Library. Grey academic studies were also identified from the references of the included literature. There was no language restriction. The pooling of data was carried out by using RevMan 5.1. RESULTS: Three randomized controlled trials (RCTs) and two non-RCTs involving 1614 patients met the inclusion criteria. Current meta-analysis indicated that there were no significant differences in terms of total blood loss (MD = -30.04, 95% CI: -114.67 to 54.59, P = 0.49), postoperative hemoglobin level (MD = -0.29, 95% CI: -0.68 to 0.10, P = 0.14), transfusion rate (RD = -0.02, 95% CI: -0.5 to -0.00, P = 0.09), length of stay ((MD = -0.14, 95% CI: -0.30 to 0.01, P = 0.07) or operation time ((MD = 1.00, 95% CI: -0.31 to 2.31, P = 0.14) between treatment groups. No significant differences were found regarding the incidence of adverse effects such as wound infection (RD = -0.01, 95% CI: -0.06 to 0.04, P = 0.66), myocardial infarction (MI) (RD = -0.01, 95% CI: -0.04 to 0.02, P = 0.61), deep venous thrombosis (DVT) (RD = 0.00, 95% CI: -0.01 to 0.01, P = 0.51) or pulmonary embolism (PE) (RD = RD = 0.00, 95% CI: -0.01 to 0.01, P = 0.63) between groups. CONCLUSION: The topical administration of TXA in THA carried similar hemostasis effects compared with intravenous use without an increased risk of thrombotic complications. No other adverse effect was identified. Topical TXA application was a simple, safe, effective and cost-effective adjunct for blood management following primary THA. For patients with a high risk of thromboembolic events, there may be benefits with topical administration. PMID- 27262882 TI - Low vs. standard dose computed tomography in suspected acute appendicitis: Is it time for a change? AB - BACKGROUND: Clinical diagnosis is accurate in only 80% of patients with suspected appendicitis with negative appendectomy rates of up to 21%. In the UK the use of standard-dose CT (SDCT) is conservative due to concerns over radiation exposure and resource implications. The use of low dose computer tomography (LDCT) instead of standard dose computer tomography (SDCT) may partially address these concerns. AIM: To compare LDCT and SDCT in the diagnosis of appendicitis. METHODS: A literature search of the EMBASE and MEDLINE databases in July 2015 was conducted using the keywords 'low dose CT' and 'appendicitis'. Data were analysed and p values calculated using the Chi-square test. P values less than 0.05 were considered to be significant. RESULTS: LDCT (1.2-5.3 mSv) was not inferior to SDCT (5.2-10.2 mSv) in the diagnosis of acute appendicitis and proposing alternative diagnoses. SDCT was superior to LDCT in the negative predictive value of diagnosis of appendiceal perforation. There was no significant difference between LDCT and SDCT in negative appendectomy rate, appendiceal perforation rate and the need for additional imaging. CONCLUSION: LDCT is not inferior to SDCT in the diagnosis of acute appendicitis and proposing alternative diagnoses. Further studies are recommended to further assess the potential role of LDCT & its cost effectiveness. Its use may improve the current management of patients with suspected acute appendicitis. PMID- 27262883 TI - Immune responses to different patterns of exposure to ovalbumin in a mouse model of allergic rhinitis. AB - Allergic rhinitis (AR) has been a significant healthcare burden on individuals and society. However, the detailed effect of different patterns of allergen exposure on the development of AR remains controversial. A mouse model of AR was established to address the complex relationships between allergen exposure and the development of AR. Allergic symptom, OVA-specific IgE in serum and nasal lavage fluid, allergic inflammation in nasal tissues were evaluated after intranasal sensitization and challenge of ovalbumin (OVA) in mice treated with two different doses of allergen for different sensitized durations. Exposure to different doses and sensitized durations of OVA were capable of inducing allergic nasal response. Repetitive OVA exposure in the sensitization phase induced the recruitment of eosinophils and goblet cell hyperplasia. The level of OVA-specific IgE in serum depended on OVA exposure and was mediated in a duration-related manner. In addition, mice treated with low-dose OVA for prolonged duration manifested the major features of human local allergic rhinitis. There were dose- and duration-related effects of allergen exposure on the development of AR. LAR was associated with repetitive exposure to low-dose allergen. Thus, allergen avoidance should be an important aim of AR management. PMID- 27262884 TI - Steroid hormones in bovine oviductal fluid during the estrous cycle. AB - Ovarian steroid hormones are major regulators of the physiology of the oviduct and reproductive events occurring within the oviduct. To establish a whole steroid profiling of the bovine oviductal fluid (OF) during the estrous cycle, contralateral and ipsilateral (to the corpus luteum or preovulatory follicle) oviducts were classified into four stages of the estrous cycle (n = 18-27 cows per stage): postovulatory (Post-ov), mid-luteal (Mid-lut), late luteal (Late lut), and preovulatory on the basis of the ovarian morphology and intrafollicular steroid concentrations. Steroids were extracted from pools of 150 to 200 MUL OF (three to 10 cows per pool; three to four pools per "stage * side" group), purified, fractioned by high-performance liquid chromatography, and analyzed by gas chromatography coupled with tandem mass spectrometry. The concentrations of progesterone (P4) in ipsilateral OF increased from Post-ov (56.9 +/- 13.4 ng/mL) to Mid-lut (120.3 +/- 34.3 ng/mL), then decreased from Late-lut (76.7 +/- 1.8 ng/mL) to Pre-ov (6.3 +/- 1.7 ng/mL), and were four to 16 times higher than in contralateral OF. Most P4 metabolites followed similar patterns of variation. Concentrations of 17beta-estradiol (E2) were significantly higher at Pre-ov (290.5 +/- 63.2 pg/mL) compared with all other stages (<118.3 pg/mL), with no difference regarding the side of ovulation. Concentrations of androstenedione displayed a pattern similar to that of E2, whereas other androgens, estrone, and corticoids did not vary between stages or sides. In conclusion, a highly concentrated and fluctuating hormonal environment was evidenced in the bovine OF. These results could be useful to improve media for IVF, embryo development, and culture of oviductal cells. PMID- 27262885 TI - Pregnancy prediction on the day of embryo transfer (Day 7) and Day 14 by measuring luteal blood flow in dairy cows. AB - This study aimed to assess the suitability of luteal blood flow analyses measured by color Doppler ultrasonography (CDUS), to predict pregnancy at pre- and post embryo transfer (ET) in dairy cows, and to compare with the established criterion like luteal size and plasma progesterone (P4) concentrations. Lactating Holstein cows (n = 65) with spontaneous (n = 34) or synchronized estrus (n = 31) were examined. Cows with a CL greater than or equal to 20 mm in diameter (n = 58) received embryo transfer on Day 7 (Day 0 = estrus). Brightness mode images were captured for calculation of the CL area, luteal cavity area, and dominant follicle area on Days 3, 5, 7, and 14. Color Doppler ultrasonography examinations were conducted to determine the blood flow area (BFA) within the CL at the maximum diameter and the time-averaged maximum velocity (TAMV) of the base of the spiral artery on the same days. Plasma P4 concentrations were determined from blood samples collected at each ultrasound examination. Pregnancy was diagnosed by an ultrasound on Day 30. There was no significant difference in the proportion of cows received embryo (91.2% vs. 87.1%, P = 0.70) and pregnancy rate (58.1% vs. 59.3%, P = 1.00) between the spontaneous estrus and synchronized groups. The BFA values of the pregnant group (n = 34) were approximately 1.42 and 1.54 times higher than those of the nonpregnant group (n = 24) on Days 7 (0.54 +/- 0.04 cm(2) vs. 0.38 +/- 0.02 cm(2); P < 0.01) and 14 (0.80 +/- 0.23 cm(2) vs. 0.52 +/- 0.22 cm(2); P < 0.01), respectively. The TAMV of the pregnant group was approximately 1.45 times higher than that of the nonpregnant group on Day 14 (57.8 +/- 3.5 cm/s vs. 40.0 +/- 3.3 cm/s; P < 0.01). However, no differences were found in the CL area, CL tissue area, dominant follicle area, and plasma P4 concentrations among these groups. In addition, the best logistic regression model to predict pregnancy included scores for BFA on Day 7, BFA and TAMV on Day 14. Setting the cutoff value of BFA at 0.43 cm(2) yielded the highest sensitivity (79.4%) and specificity (75.0%) on Day 7, indicating the effectiveness of using BFA data for predicting pregnancy on Day 7. Furthermore, setting the cutoff value at one obtained from a sample with BFA 0.63 cm(2) and TAMV 50.60 cm/s yielded the highest sensitivity (85.3%) and specificity (91.7%) on Day 14. In conclusion, the evaluations of BFA on Day 7, and paired BFA and TAMV on Day 14 represent reliable predictors of pregnancy in the cow. PMID- 27262886 TI - Dietary conjugated linoleic acid supplementation alters the expression of genes involved in the endocannabinoid system in the bovine endometrium and increases plasma progesterone concentrations. AB - Endocannabinoids are derived from phospholipids and reduce fertility by interfering with implantation. Identification of changes in the expression of genes of the endocannabinoid system as a result of dietary inclusion of conjugated linoleic acid (CLA) is critical to the advancement of our understanding of the nutritional regulation of uterine function. An experiment was conducted on transition cows to evaluate the expression of key endocannabinoid genes in bovine endometrium in response to dietary supplementation with CLA. A total of 16 cows were randomly assigned to two treatments: (1) control (75 g/day palm oil) and (2) CLA (75 g/day CLA) from 21 days prepartum to Day 42 postpartum. Cows underwent uterine biopsy on days 21 and 42 postpartum. The abundance of mRNA encoding endocannabinoid receptor (CNR2), N acyl phosphatidylethanolamine phospholipase D (NAPEPLD), fatty acid amide hydrolase (FAAH), N-acylethanolamine acid amidase (NAAA), and monoglyceride lipase (MGLL) was measured by real-time PCR. Results reported that relative levels of mRNA encoding CNR2 and NAPEPLD were decreased (P < 0.05) compared with control cows between Days 21 and 42 postpartum. Relative levels of mRNA coding for NAAA and MGLL were not different (P > 0.05) in the same situation. Mean plasma progesterone concentrations were higher in CLA-fed cows compared with control cows at Day 42 postpartum (3.51 and 1.42 ng/mL, respectively, P < 0.05). In conclusion, we suggest that the beneficial effects of a diet enriched with CLA are the result of a decrease in relative gene expression of the endocannabinoid receptor (CNR2) and enzymes that synthesize fatty acid amides (NAPEPLD) and of an increase in the expression of PTGS2 that in turn can oxidate endocannabinoids and consequently resulted in increased plasma progesterone concentrations during early lactation. PMID- 27262887 TI - Concomitant application of sprint and high-intensity interval training on maximal oxygen uptake and work output in well-trained cyclists. AB - PURPOSE: In this study, we compared the effects of two different training modalities on maximal oxygen uptake and work output. METHODS: Participants included 26 well-trained mountain bike cyclists were divided into two groups. The first group trained using a conventional endurance protocol at steady-state (moderate) intensity and variable-intensity (high-moderate-low) free of maximal efforts. The second group combined endurance training with a sprint and high intensity interval training protocol, which, respectively, were based on 30 s maximal repetitions and 4 min high intensity repetitions. Training duration was 8 weeks. A graded exercise test was administered pre- and post-training. Work output, oxygen uptake, minute pulmonary ventilation, heart rate and stroke volume were determined during the test. RESULTS: While work output significantly increased post-training in both groups (P < 0.05), the interval training group showed a greater magnitude of change (from 284.4 +/- 91.9 to 314.2 +/- 95.1 kJ) than the endurance training group (from 271.8 +/- 73.3 to 283.4 +/- 72.3 kJ). Significant increases in maximal oxygen uptake (from 57.9 +/- 6.8 to 66.6 +/- 5.3 ml kg(-1) min(-1)), maximal pulmonary ventilation and stroke volume were observed only in the interval training group. CONCLUSIONS: An exercise protocol involving endurance and sprint and high-intensity interval training was found to induce positive effects on maximal oxygen uptake in a group of well-trained cyclists with several years athletic experience. PMID- 27262888 TI - Cortisol and testosterone dynamics following exhaustive endurance exercise. AB - PURPOSE: Cortisol (C) and testosterone (T) are impacted significantly by prolonged endurance exercise with inverse responses. Increases in C are witnessed concurrently with decrements in T, possibly impacting recovery. This study was conducted to assess the dynamics of C and free T (fT) concentration and recovery time following an exhaustive endurance exercise session (EES). METHODS: 12 endurance-trained males (X +/- SD: VO2max 66.3+/-4.8 ml/kg/min, age 22.8 +/- 3.1 years, body fat 11.0 +/- 1.4 %, training 7.1 +/- 3.2 years) completed a treadmill EES at ventilatory threshold (74.7 +/- 4.6 % of VO2max; 96.9 +/- 10.8 min). Basal blood C and fT were collected at baseline: -48, -24 h, and immediately before (0 h) the EES as well as immediately (+0 h), +24 h, +48 h, and +72 h after the EES. Blood glucose (G) was measured to confirm no undue influence on C. Statistically data were analyzed with repeated measures ANOVA (LSD post hoc). RESULTS: C (nmol/L) increased significantly from -48 h (321 +/- 59) to +0 h (701 +/- 178) (p < 0.001), and displayed a baseline overshoot with +24 h (209 +/- 67) being significantly lower than -48 and +0 h (p < 0.03). fT (pmol/L) decreased significantly from -48 h (161 +/- 40) to +0 h (106 +/- 38) (p < 0.01) and remained lower at +24 h (110 +/- 33) and +48 h (129 +/- 30) (p < 0.001). G remained stable throughout. A moderately negative correlation (r = -0.636, p < 0.026) was found between C and fT at +0 h. CONCLUSIONS: EES recovery may require 48 h for C and 72 h for fT to return to baseline values. Furthermore, C and fT were only correlated immediately post-exercise. Future research should perform more frequent measurements throughout time course. PMID- 27262889 TI - Erratum to Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse [Bone 87 (2016) 161-168]. PMID- 27262890 TI - Corrigendum to "Trabecular microfractures in the femoral head with osteoporosis: Analysis of microcallus formations by synchrotron radiation micro CT" [Bone, volume 64 (2014) 82-87]. PMID- 27262891 TI - Covered self-expanding metal stents for the management of common bile duct stones. AB - BACKGROUND AND AIMS: Little medical literature exists for the use of fully covered self-expanding metal stents (CSEMSs) in the management of retained common bile duct (CBD) stones. Our aim was to assess the safety and efficacy of CSEMSs for the indication of retained "difficult" CBD stones. METHODS: This retrospective cases series included 44 patients (30 women; median age, 69 years [range, 24-88]) who underwent CSEMS insertion for the indication of retained "difficult" CBD stones in 2 tertiary referral centers. Patients underwent temporary placement of CSEMSs after incomplete stone clearance at ERCP. Follow-up ERCP was arranged for stent removal and subsequent attempt at duct clearance. Procedure-related adverse events were also recorded. RESULTS: Successful biliary drainage was achieved in all cases after CSEMS placement. Forty-two stents were removed with successful duct clearance achieved in 36 cases (82%) after a median in-stent duration of 8 weeks. There were 10 cases (22.7%) of stent migration, all noted incidentally during follow-up. One patient died of nonbiliary causes before attempted removal. CONCLUSION: This is the largest published retrospective case series for use of CSEMSs for management of retained CBD stone disease to date. We have shown high success rates for this indication. A well-designed, multicenter, randomized controlled trial might address the uncertainty of cost-to-benefit ratio and appropriate duration for CSEMSs to be left in situ. Specific stent modification for this indication, including wider distal flare and retrieval purse string loop, may also be useful. PMID- 27262892 TI - Exercise therapy after ultrasound-guided corticosteroid injections in patients with subacromial pain syndrome: a randomized controlled trial. AB - BACKGROUND: Subacromial pain syndrome (SAPS) accounts for around 50 % of all cases of shoulder pain. The most commonly used treatments are glucocorticosteroid (steroid) injections and exercise therapy; however, despite treatment SAPS patients often experience relapse of their symptoms. Therefore the clinical effect of combining steroid and exercise therapy is highly relevant to clarify. The aim of this randomized controlled trial was to investigate if exercise therapy added to steroid injection in patients with SAPS will improve the effect of the injection therapy on shoulder pain. METHODS: In this two-arm randomized trial running over 26 weeks, patients with unilateral shoulder pain (> 4 weeks) and thickened subacromial bursa (> 2 mm on US) were included. At baseline all participants received two steroid injections into the painful shoulder with an interval of one week. Subsequently they were randomized (1:1) to either 10 weeks exercise of the involved shoulder (intervention group) or exercise of the uninvolved shoulder (control group). The patients were re-examined after the exercise program (at week 13) and again at week 26. The primary outcome assessed after 26 weeks was change in shoulder pain analyzed using the intention-to-treat principle (non-responder imputation). RESULTS: Ninety-nine SAPS patients (58 female) participated (49 intervention/50 control). At both follow up visits (week 13 and 26) no statistically significant between-group differences in pain changes on a visual analog scale (mm) were seen (13 weeks: pain at rest 1.7 (95 % CI -3.6 to 7.0; P = 0.53); pain in activity 2.2 (95 % CI -6.5 to 10.9; P = 0.61), 26 weeks: rest 5.6 (95 % CI -0.9 to 12.1; P = 0.09); activity 2.2 (95 % CI -6.8 to 11.2; P = 0.62). The reduction in pain was most evident in the control group at all four pain measurements. The only difference between groups was seen by US examination at week 13, where fewer participants with impingement were observed in the intervention group compared with the controls (9 vs. 19 participants; P = 0.03). CONCLUSION: Exercise therapy in the painful shoulder in SAPS patients did not improve the effectiveness of steroid injections for shoulder pain in patients with unilateral SAPS and enlarged subacromial bursa on US examination. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01506804 ). Registration date 5 May 2011. PMID- 27262893 TI - SW43-DOX +/- loading onto drug-eluting bead, a potential new targeted drug delivery platform for systemic and locoregional cancer treatment - An in vitro evaluation. AB - Treatment of unresectable primary cancer and their distant metastases, with the liver representing one of the most frequent location, is still plagued by insufficient treatment success and poor survival rates. The Sigma-2 receptor is preferentially expressed on many tumor cells making it an appealing target for therapy. Thus, we developed a potential targeted drug conjugate consisting of the Sigma-2 receptor ligand SW43 and Doxorubicin (SW43-DOX) for systemic cancer therapy and for locoregional treatment of primary and secondary liver malignancies when loaded onto drug-eluting bead (DEB) which was compared in vitro to the treatment with Doxorubicin alone. SW43-DOX binds specifically to the Sigma 2 receptor expressed on hepatocellular (Hep G2, Hep 3B), pancreatic (Panc-1) and colorectal (HT-29) carcinoma cell lines with high affinity and subsequent early specific internalization. Free SW43-DOX showed superior concentration and time depended cancer toxicity than treatment with Doxorubicin alone. Action mechanisms analysis revealed an apoptotic cell death with increased caspase 3/7 activation and reactive oxygen species (ROS) production. Only ROS scavenging with alpha Tocopherol, but not the caspase inhibition (Z-VAD-FMK), partly reverted the effect. SW43-DOX could successfully be loaded onto DEB and showed prolonged eluting kinetics compared to Doxorubicin. SW43-DOX loaded DEB vs. Doxorubicin loaded DEB showed a significantly greater time dependent toxicity in all cell lines. In conclusion, the novel conjugate SW43-DOX +/- loading onto DEB is a promising drug delivery platform for targeted systemic and locoregional cancer therapy. PMID- 27262894 TI - Angiotensinogen and HLA class II predict bevacizumab response in recurrent glioblastoma patients. AB - BACKGROUND: Bevacizumab combination therapy is among the most frequently used treatments in recurrent glioblastoma and patients who achieve response to bevacizumab have improved survival as well as quality of life. Accordingly, the aim of this study was to identify predictive biomarkers for bevacizumab response in recurrent glioblastoma patients. METHODS: The study included a total of 82 recurrent glioblastoma patients treated with bevacizumab combination therapy whom were both response and biomarker evaluable. Gene expression of tumor tissue was analyzed by using a customized NanoString platform covering 800 genes. Candidate gene predictors associated with response were analyzed by multivariate logistic and Cox regression analysis. RESULTS: Two genes were independently associated with response: Low expression of angiotensinogen (2-fold decrease in AGT; OR = 2.44; 95% CI: 1.45-4.17; P = 0.0009) and high expression of a HLA class II gene (2-fold increase in HLA-DQA1; OR = 1.22; 95% CI: 1.01-1.47; P = 0.04). These two genes were included in a model that is able predict response to bevacizumab combination therapy in clinical practice. When stratified for a validated prognostic index, the predictive model for response was significantly associated with improved overall survival. CONCLUSION: Two genes (low angiotensinogen and high HLA-class II expression) were predictive for bevacizumab response and were included in a predictive model for response. This model can be used in clinical practice to identify patients who will benefit from bevacizumab combination therapy. PMID- 27262895 TI - Phase 2 Trial of Metformin Combined With 5-Fluorouracil in Patients With Refractory Metastatic Colorectal Cancer. AB - BACKGROUND: Observational and preclinical studies have suggested that metformin has antitumor effects in solid tumors, including colorectal cancer (CRC). However, the effects of metformin in CRC have not been tested in clinical trials. PATIENTS AND METHODS: This was a single-center, single-arm phase 2 clinical trial where histologically confirmed CRC patients with measurable and progressing metastatic disease previously treated with 5-fluorouracil (5-FU), irinotecan, oxaliplatin, and an anti-epidermal growth factor receptor (if the tumor was RAS wild type) were enrolled to receive metformin 850 mg orally continuously 2 times a day plus 5-FU 425 mg/m2 and leucovorin 50 mg intravenously weekly until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was disease control rate at 8 weeks. RESULTS: Among 50 patients included, 11 (22%) met the primary end point. The median progression-free survival was 1.8 months and the median overall survival 7.9 months. Analyzing only the 11 patients who experienced disease control at 8 weeks, their median progression-free survival was 5.6 months and their median overall survival was 16.2 months. There was a trend for prolonged median survival for obese patients (12.4 vs. 5.8 months) and those longer off 5-FU. The treatment was well tolerated; the main adverse effects were diarrhea, nausea, vomiting, and myelotoxicity. CONCLUSION: Metformin and 5-FU showed an overall modest but intriguing activity in patients with refractory CRC in this phase 2 study. Some patients experienced long-term disease control. Further trials are needed to confirm these results, particularly in obese patients with CRC. PMID- 27262898 TI - Training law enforcement to respond to opioid overdose with naloxone: Impact on knowledge, attitudes, and interactions with community members. AB - BACKGROUND: Training law enforcement officers (LEOs) to administer naloxone to opioid overdose victims is increasingly part of comprehensive efforts to reduce opioid overdose deaths. Such efforts could yield positive interactions between LEOs and community members and might ultimately help lower overdose death rates. METHODS: We evaluated a pilot LEO naloxone program by (1) assessing opioid overdose knowledge and attitudes (competency in responding, concerns about naloxone administration, and attitudes towards overdose victims) before and after a 30min training on overdose and naloxone administration, and (2) conducting qualitative interviews with LEOs who used naloxone to respond to overdose emergencies after the training. RESULTS: Eighty-one LEOs provided pre- and post training data. Nearly all (89%) had responded to an overdose while serving as an LEO. Statistically significant increases were observed in nearly all items measuring opioid overdose knowledge (p's=0.04 to <0.0001). Opioid overdose competencies (p<0.001) and concerns about naloxone administration (p<0.001) significantly improved after the training, while there was no change in attitudes towards overdose victims (p=0.90). LEOs administered naloxone 11 times; nine victims survived and three of the nine surviving victims made at least one visit to substance abuse treatment as a result of a LEO-provided referral. Qualitative data suggest that LEOs had generally positive experiences when they employed the skills from the training. CONCLUSIONS: Training LEOs in naloxone administration can increase knowledge and confidence in managing opioid overdose emergencies. Perhaps most importantly, training LEOs to respond to opioid overdose emergencies may have positive effects for LEOs and overdose victims. PMID- 27262897 TI - Personality profile of binge drinking in university students is modulated by sex. A study using the Alternative Five Factor Model. AB - BACKGROUND: The prevalence of binge drinking (BD), found especially among young people, is increasing worldwide and has become an important social and health concern. We studied, for the first time, the personality profile, using the Alternative Five Factor Model, among university students with BD and healthy controls, taking into account the possible influence of sex. METHODS: 70 participants with BD (30 men) and 70 healthy controls (30 men) were included, selected to control for characteristics that are known to be related to BD (physical and mental disorders, consumption of other drugs, circadian rhythms), completed the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). RESULTS: The scores on Neuroticism-Anxiety and Impulsive Sensation-Seeking were higher in the BD group compared to the controls (p<0.001 in both cases). The higher scores in the BD group in Neuroticism-Anxiety are due to higher scores in the women's group (p=0.014), while those in Impulsive Sensation-Seeking are due to higher scores in the men's group (p=0.009), both in the Impulsivity and in the Sensation-Seeking subscales (p<0.045). CONCLUSIONS: Sex could be a factor that modulates the endophenotype of drug dependence (impulsive and anxious personality) and the prevention and/or treatment programs for BD should include not only the management of the personality risk factors but also different tailored approaches according to sex. PMID- 27262899 TI - Tobacco control policy and socio-economic inequalities in smoking in 27 European countries. AB - BACKGROUND: Higher Tobacco Control Scale (TCS) scores, in the early 2000s were associated with higher smoking cessation rates across Europe, both among lower and higher educated people. We aimed to assess if this association held in recent years. METHODS: Repeated cross-sectional Eurobarometer surveys were used, in 27 European countries from 2006 to 2012 (study sample=73,617 adults). We used multilevel regression to model associations between the TCS (ranging from 0 to 100, quantifying: tobacco price, smoke-free laws, mass-media campaigns, advertising bans, warning labels, and cessation support) and both smoking cessation and cigarettes smoked per day. We modelled associations according to respondents' education and occupation, with adjustment for age, sex, and survey wave. RESULTS: We found no association between the TCS and smoking cessation for lower or middle educated respondents, but we did find an association for higher educated respondents (OR: 1.13, 95%CI: 1.08 to 1.19). For smoking intensity, we observed no associations with the TCS for lower educated respondents (beta: 0.04, 95%CI: -0.33 to 0.41) but we did observe significant associations for middle (beta: -0.25, 95%CI: -0.47 to -0.03) and higher educated respondents (beta: 0.27, 95%CI: -0.55 to -0.01). Associations were observed for both manual and non manual classes, but not for those not working for pay. Of the TCS domains, none were associated with smoking cessation for lower educated respondents, but five were for higher educated respondents. CONCLUSIONS: Associations between tobacco control policies and smoking cessation were found mostly among higher socioeconomic groups. This underlines the need for specific tobacco control policies that explicitly focus on reaching low socio-economic groups. PMID- 27262896 TI - Pancreas Adenocarcinoma: Ascites, Clinical Manifestations, and Management Implications. AB - BACKGROUND: Ascites develops in a subset of patients with pancreatic adenocarcinoma (PAC) at presentation or as the disease advances. Limited data exist on the prognostic importance of malignant ascites in PAC. Our hypothesis is that this information will provide an understanding of the natural history and facilitate management decisions. METHODS: We conducted a retrospective analysis of 180 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between January 1, 2009 and December 31, 2014, with PAC and with ascites either at presentation or that developed during the disease course. RESULTS: For the 180 patients, the overall survival was 15 months. The time from diagnosis to ascites presentation was 11 months, and the survival time after ascites development was 1.8 months (range, 1.6-2.3 months; 95% confidence interval). Of 62 patients (34%) who had ascitic fluid analyzed, 36 (58%) had positive cytology. Fifty-one (82%) patients had a serum ascites albumin gradient >= 1, and 11 (18%) had serum ascites albumin gradient < 1. Sixty-four (36%) patients had their ascites managed solely by serial paracenteses. A total of 116 patients required a catheter; of these, 108 (93%) had a Tenckhoff catheter, 4 (3%) a Pleurx catheter, 4 (3%) a pigtail catheter, and 1 (1%) a Denver catheter. Eight (7%) patients required 2 catheters to be placed, and in 6 (5%), Tenckhoff catheters had to be removed. The main observed complications were spontaneous bacterial peritonitis in 7 (11%) managed with paracenteses versus 26 (23%) who had a catheter placed, catheter malfunction in 8 (7%), and acute renal failure in 6 (3%). After ascites development, 79 (44%) patients received active anti-cancer therapy, and 101 (56%) patients were managed with supportive care alone. CONCLUSIONS: In patients with PAC who presented with or developed ascites, serial paracenteses and indwelling catheters are common methods used for providing symptomatic relief. The complication rate was higher with indwelling catheters, primarily related to infection (eg, bacterial peritonitis). Overall, ascites has a significantly negative prognostic import with a short median survival. PMID- 27262900 TI - Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity. AB - Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7) and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy. PMID- 27262901 TI - Metformin enhances anti-tumor effect of L-type amino acid transporter 1 (LAT1) inhibitor. AB - BACKGROUND: In many cancer cells, L-type amino acid transporter 1 (LAT1) transports neutral amino acids with bulky side chain, which activate mammalian target of rapamycin (mTOR) to cause cell proliferation. An anti-diabetic drug, metformin, has been shown to activate AMP-activated protein kinase (AMPK), which leads to inhibition of mTOR. LAT1 inhibition in combination with metformin could result in more prominent suppression of mTOR activity. PURPOSE: Anti proliferative effect of a newly developed LAT1 specific inhibitor JPH203 in combination with metformin is evaluated in 2 head and neck cancer cell lines, Ca9 22 and HEp-2 cells and in nude mice inoculated with Ca9-22 cells. RESULTS AND DISCUSSION: By MTT assay, 0.5 mM metformin inhibited proliferation of Ca9-22 cells to 70% of control. In the presence of 100 MUM JPH203, proliferation of Ca9 22 cells was inhibited to 60% of control. By combining these 2 drugs, proliferation of Ca9-22 was significantly inhibited to 40% of control. However, this regimen was not very effective against HEp-2 cells. This combination also suppressed in vivo growth of Ca9-22 cells in a xenotransplant model. A combination of anti-LAT1 drug with metformin may be an effective anti proliferative therapy for certain subsets of cancers. PMID- 27262902 TI - Possibility as an anti-cancer drug of astemizole: Evaluation of arrhythmogenicity by the chronic atrioventricular block canine model. AB - Since astemizole in an oral dose of 50 mg/kg/day was recently reported to exert anti-cancer effect in mice, we evaluated its proarrhythmic potential using the atrioventricular block dogs in order to clarify its cardiac safety profile. An oral dose of 3 mg/kg prolonged the QT interval without affecting the QTc (n = 4), whereas that of 30 mg/kg increased the short-term variability of repolarization and induced premature ventricular contractions in each animal, resulting in the onset of torsade de pointes in 1 animal (n = 4). Thus, proarrhythmic dose of astemizole would be lower than anti-cancer one, limiting its re-profiling as an anti-cancer drug. PMID- 27262903 TI - Identification and functional analysis of choline transporter in tongue cancer: A novel molecular target for tongue cancer therapy. AB - We examined the functional characteristics of choline uptake in human tongue carcinoma using the cell line HSC-3. Furthermore, we explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. Both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were expressed, and were located in plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is pH-dependent. Several cationic drugs inhibited cell viability and [(3)H]choline uptake. Choline uptake inhibitors and choline deficiency inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1 that relies on a directed H(+) gradient as a driving force. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be the major site for the control of choline oxidation in mitochondria and hence for the supply of endogenous betaine and S-adenosyl methionine, which serves as a major methyl donor. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for tongue cancer therapy. PMID- 27262904 TI - A novel rare sugar inhibitor of murine herpes simplex keratitis. AB - PURPOSE: To determine the therapeutic efficacy of a novel rare sugar, l-psicose, for the treatment of HSV-1 induced herpetic stromal keratitis (HSK) in a mouse eye model. METHODS: One rare sugar l-psicose was assayed for HSV-1 inhibition of in vitro virus adsorption. The IC50 and IC90 values of l-psicose were determined using plaque reduction assay (PRA) in CV-1 cell. Female Balb/c mice were corneally infected with HSV-1, strain KOS-GFP; A topical eye drop treatment of l psicose was started 24 h after infection and continued four times daily for ten consecutive days. The severity of HSK was monitored by slit lamp examination in a masked fashion and Infectious HSV-1 shedding was determined by PRA. RESULTS: l psicose was found to have anti-viral activity in vitro at an IC50 dose of 99.5 mM and an IC90 dose of 160 mM. Topical eye drop treatment with 200 mM l-psicose in PBS solution significantly reduced the severity of HSK compared to the mock treatment group. The in vivo mouse ocular model results of l-psicose therapy correlated with accelerated clearance of virus from eye swabs. CONCLUSION: The results suggest that topical treatment with rare sugar l-psicose has efficacy against HSK through inhibition of HSV-1. PMID- 27262905 TI - In vivo analysis of torsadogenic potential of an antipsychotic drug paliperidone using the acute atrioventricular block rabbit as a proarrhythmia model. AB - We assessed electrophysiological effects of an atypical antipsychotic drug paliperidone in acute atrioventricular block rabbits. Intravenous administration of paliperidone at a clinically relevant dose (0.06 mg/kg) hardly affected the QT interval or monophasic action potential (MAP) duration, and the higher doses (0.6 and 6 mg/kg) prolonged the QT interval and MAP duration. Meanwhile, premature ventricular contractions with R on T phenomenon were observed in 3 out of 6 animals at the middle dose, and torsades de pointes (TdP) episodes were detected in 2 out of 6 animals at the high dose. Intravenous administration of its chemically related compound risperidone at a clinically relevant dose (0.03 mg/kg) hardly affected the electrophysiological parameters, and the higher doses (0.3 and 3 mg/kg) prolonged the QT interval and MAP duration. Meanwhile, the premature ventricular contractions with R on T were observed in 2 out of 6 animals at the middle dose, and TdP episodes were detected in 4 out of 6 animals at the high dose. These results suggest that paliperidone showed torsadogenic potential at supra-therapeutic doses, whose potency can be estimated to be equal or slightly subordinate in comparison with that of risperidone. PMID- 27262906 TI - Interventions to improve patient hand hygiene: a systematic review. AB - Nosocomial pathogens may be acquired by patients via their own unclean hands, but there has been relatively little emphasis on patient hand hygiene as a tool for preventing healthcare-associated infections (HCAIs). The aim of this systematic review was to determine the efficacy of patient hand hygiene interventions in reducing HCAIs and improving patient hand hygiene rates compared to usual care. Electronic databases and grey literature were searched to August 2014. Experimental and quasi-experimental studies were included if they evaluated a patient hand hygiene intervention conducted in an acute or chronic healthcare facility and included HCAI incidence and/or patient hand hygiene rates as an outcome. All steps were performed independently by two investigators. Ten studies were included, most of which were uncontrolled before-after studies (N=8). The majority of interventions (N=7) were multi-modal, with components similar to healthcare worker hand hygiene programmes, including education, reminders, audit and feedback, and provision of hand hygiene products. Six studies reported HCAI outcomes and four studies assessed patient hand hygiene rates; all demonstrated improvements but were at moderate to high risk of bias. In conclusion, interventions to improve patient hand hygiene may reduce the incidence of HCAIs and improve hand hygiene rates, but the quality of evidence is low. Future studies should use stronger designs and be more selective in their choice of outcomes. PMID- 27262907 TI - Patient-reported outcome studies in hospitalized patients isolated due to multi drug-resistant organisms: how representative are they and who can be included in respective studies? PMID- 27262908 TI - Survival Implications of Variation in the Thoroughness of Pathologic Lymph Node Examination in American College of Surgeons Oncology Group Z0030 (Alliance). AB - BACKGROUND: Accurate pathologic nodal staging mandates effective collaboration between surgeons and pathologists. The American College of Surgeons Oncology Group Z0030 trial (ACOSOG Z0030) tightly controlled surgical lymphadenectomy practice but not pathologic examination practice. We tested the survival impact of the thoroughness of pathologic examination (using the number of examined lymph nodes as a surrogate). METHODS: We re-analyzed the mediastinal lymph node dissection arm of ACOSOG Z0030, using logistic regression and Cox proportional hazards models. RESULTS: Of 513 patients, 435 were pN0, 60 were pN1, and 17 were pN2. The mean number of mediastinal lymph nodes examined was 13.5, 13.1, and 17.1; station 10 lymph nodes were 2.4, 2.7, and 2.6; station 11 to 14 nodes were 4.6, 6.1, and 6.7; and total lymph nodes were 19.7, 21.3, and 25.4 respectively. The pN category and histologic evaluation were associated with increased number of examined intrapulmonary lymph nodes. Patients with pN1 had more non-hilar N1 nodes than patients with pN0, patients with N2 had more N2 nodes examined than patients with pN0 or pN1. Patients with pN0 had better survival with examination of more N1 nodes; patients with pN1 had better survival with increased mediastinal nodal examination; the likelihood of discovering N2 disease was significantly associated with increased examination of mediastinal and non-hilar N1 lymph nodes. CONCLUSIONS: Despite rigorously standardized surgical hilar/mediastinal lymphadenectomy, the number of lymph nodes examined was associated with the likelihood of detecting nodal metastasis and survival. This may indicate an effect of incomplete pathologic examination. PMID- 27262909 TI - The Feasibility of Median Sternotomy With or Without Thoracotomy for Locally Advanced Non-Small Cell Lung Cancer Treated With Induction Chemoradiotherapy. AB - BACKGROUND: This study aimed to compare the morbidity and mortality of a median sternotomy approach and a lateral thoracotomy and to investigate the feasibility of a median sternotomy for locally advanced non-small cell lung cancer (NSCLC) after induction chemoradiotherapy. METHODS: The medical records of patients with locally advanced NSCLC who underwent induction chemoradiotherapy followed by surgery at our institution between January 1999 and September 2014 were reviewed. We compared the morbidity and mortality of a median sternotomy approach and a lateral thoracotomy. RESULTS: A total of 102 NSCLC patients were the subjects of this study. Among them, 31 patients underwent surgery with a median sternotomy approach and 71 patients underwent surgery with a lateral thoracotomy. Patients in the median sternotomy group had a significantly higher rate of postoperative arrhythmia than those in the lateral thoracotomy group (p = 0.0028). However, all the complications were manageable, and no treatment-related deaths occurred in the median sternotomy group. Regarding the prognosis, the 5-year overall survival rate was 72.7%, and the 2-year recurrence-free survival rate was 66.5% in the entire population. No significant differences in overall survival or recurrence free survival were observed between the 2 approaches. CONCLUSIONS: Whereas the lateral thoracotomy approach is a standard procedure, our experience suggests that a median sternotomy approach for locally advanced NSCLC after induction chemoradiotherapy is a feasible procedure and can be a surgical option. PMID- 27262910 TI - Contributions of Respiration and Heartbeat to the Pulmonary Blood Flow in the Fontan Circulation. AB - BACKGROUND: In the Fontan circulation, driving forces with respiration, heartbeat, and lower limb muscle pump are relevant. However, the mechanics of these forces has not been proven, and their effects on the Fontan circulation remain unclear. METHODS: We performed catheter examinations and measured pressure and flow velocity simultaneously in the bilateral pulmonary arteries of 12 Fontan patients 1 year after the operation. The pulmonary pressure and flow velocity data were decomposed into respiratory and heartbeat components by discrete Fourier analysis. We then calculated respiratory and cardiac wave intensity (WI) based on the respiratory and heartbeat components of pressure and flow velocity data. RESULTS: Respiratory WI formed 2 negative peaks, a backward expansion wave during the inspiratory phase, and then a backward compression wave during the expiratory phase. In 2 phrenic nerve palsy cases and 1 case of a patient on a respirator, respiratory WI showed disturbed patterns and a negative pattern, respectively. Cardiac WI showed 2 or 4 negative peaks, the time phase of which matched that of the atrial contractions. CONCLUSIONS: WI analysis elucidated that inspiration acts as a sucking driving force and increases the pulmonary blood flow in the Fontan circulation. Respiratory complications compromise efficiency in the Fontan circulation. It was also revealed that the pulmonary blood flow was mutually dammed up and sucked in by increases and decreases in atrial pressure. PMID- 27262911 TI - Impact of Moodle-Based Online Curriculum on Thoracic Surgery In-Training Examination Scores. AB - BACKGROUND: The feasibility and efficacy of a web-based curriculum in supplementing thoracic surgical training was previously shown. However, the impact of curricular participation on validated knowledge tests remains unknown. We compared in-service training examination (ITE) results among trainees, stratified by curricular use. METHODS: The national online curriculum was implemented in August 2013. We retrospectively reviewed trainees who participated in thoracic surgical training programs in both 2012 to 2013 and 2013 to 2014. Scores from the 2013 and 2014 ITEs were obtained, and curricular usage data were collected from site analytics. Trainees were separated into three groups according to 2013 ITE scores; within each group, changes in score for high- versus low-volume users were compared. RESULTS: 187 trainees took the ITE both years, with exposure to the online curriculum during only the second year. High volume users' scores trended toward greater improvement than scores of low-volume users (+18.2% versus +13.0%, p = 0.199). When stratified by 2013 score, the lowest scoring quartile improved substantially, and the highest scoring quartile improved modestly, regardless of curricular use. However, for those individuals who achieved mid-range scores in 2013, there was a trend toward much greater improvement in score with heavier use of the curriculum (+17.0% versus +7.0%, p = 0.094). CONCLUSIONS: Among trainees who had access to the novel online curriculum during the second of 2 consecutive years, we evaluated the impact of curricular participation on ITE scores. The effect appears to be most pronounced in individuals with mid-range scores, in whom high curricular use led to the greatest improvement. PMID- 27262912 TI - Branched Endovascular Therapy of the Distal Aortic Arch: Preliminary Results of the Feasibility Multicenter Trial of the Gore Thoracic Branch Endoprosthesis. AB - BACKGROUND: Endovascular treatment for aortic arch aneurysms often requires adjunctive use of hybrid debranching procedures to maintain branch vessel perfusion. This study describes early results with a novel branched arch endograft for total endovascular repair of distal arch aneurysms. METHODS: This US feasibility multicenter clinical trial evaluated 22 patients (mean age, 74.1 +/- 10.5 years; 54.5% male) undergoing branched thoracic endovascular aortic repair in Ishimaru zone 2. This endograft was designed with a single side branch designed to facilitate aortic coverage proximal to the left subclavian artery while maintaining branch vessel patency. The pathologic features treated included fusiform (n = 10) and saccular (n = 12) aneurysms, with a mean aortic diameter of 5.7 +/- 1.1 cm. The mean preoperative left-to-right brachial index was 1.0 +/- 0.1. RESULTS: The mean total treatment length was 17.6 +/- 8.9 cm; 8 patients were treated with a single 10-cm graft for isolated arch disease. The primary endpoint of device delivery and branch vessel patency was achieved in 100% of patients, without 30-day death, stroke, or permanent paraplegia. The median duration of hospitalization was 4.0 days. Type I endoleaks at completion angiography were observed in 4 patients, and all resolved by 1 month without reintervention. All side branches were patent at 1 month. The Kaplan-Meier survival rate at 6 months was 94.7%. CONCLUSIONS: Total endovascular repair of distal zone 2 arch aortic aneurysms can be achieved with a novel branched arch endograft. Future studies will evaluate the feasibility of this approach for aneurysms encompassing the brachiocephalic trunk and left carotid artery. PMID- 27262913 TI - The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2016 Update on Research. AB - The Society of Thoracic Surgeons Adult Cardiac Database (ACSD) is an international voluntary effort that is the foundation of our specialty's efforts in clinical performance assessment and quality improvement. Containing nearly 6,000,000 patient records, the ACSD is a robust resource for clinical research. Seven major original publications and four review articles were generated from the ACSD in 2015. The risk-adjusted outcome analyses and quality measures reported in these studies have made substantial contributions to inform daily clinical practice. This report summarizes the ACSD-based research efforts published in 2015. PMID- 27262914 TI - Long-Term Outcome of Arterial Switch Operation Conversion After Failed Senning/Mustard Procedure. AB - BACKGROUND: We evaluated long-term outcomes of the arterial switch operation (ASO) conversion after a failed Senning/Mustard operation among patients with dextro-transposition of the great arteries. METHODS: Between 1986 and 2006, 9 patients with dextro-transposition of the great arteries underwent ASO conversion at our institute. All patients had systemic right ventricle failure, 6 had supraventricular tachycardia, and 8 had moderate or severe tricuspid valve regurgitation. All patients had New York Heart Association classification II or III. The median age of patients at the ASO conversion operation was 7.4 years (range, 0.6 to 32.4 years). Pulmonary artery banding for left ventricle training was performed in 8 of the 9 patients before conversion. RESULTS: There was 1 early death from low-output syndrome at 5 days postoperatively and 1 late sudden death at 5 months. Median follow-up time was 23.1 years (range, 0.08 to 28.0 years). The actuarial survival rate was 76.1% at 20 years. Long-term survivors revealed good New York Heart Association classification (class I, 6 patients; class II, 1 patient), with less than mild tricuspid regurgitation and brain natriuretic peptide levels of 40.6 +/- 16.2 pg/mL. Cardiac catheterization revealed significant improvements of right ventricle end-diastolic volume (decreased from 243.2% to 117.7% of normal), and right ventricle ejection fraction (increased from 0.42 to 0.572; p < 0.05). Three patients underwent new pacemaker implantation for sick sinus syndrome, and moderate neoaortic valve regurgitation developed in 1 patient. CONCLUSIONS: Excellent long-term outcomes can be achieved after ASO conversion; however, careful observation for new-onset sick sinus syndrome and aortic regurgitation is mandatory. PMID- 27262915 TI - Prognostic Significance of Sleep Apnea Syndrome on False Lumen Aortic Expansion in Post-Acute Aortic Syndrome. AB - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a risk factor for resistant arterial hypertension and aortic dilatation. We assessed the value of systematic screening for OSAS in patients soon after the onset of acute aortic syndrome (AAS). METHODS: Between January 2010 and June 2014, patients were prospectively screened for post AAS OSAS. The severity of OSAS was defined by the Apnea-Hypopnea Index (AHI) and the Oxygen Desaturation Index (ODI). Blood pressure control was assessed with 24-h ambulatory monitoring. RESULTS: The study population comprised 71 patients (males: 64.7%; median age [interquartile range]: 57 [49 to 64] years; type A AAS: 49.3%; type B AAS: 50.7%). According to the AHI, 58 patients (81.7%) had OSAS and 31 (43.6%) had severe OSAS. A prognostic analysis revealed that the descending thoracic false lumen dilatation rate rose significantly with the severity of OSAS (p = 0.0008 for the AHI and p = 0.0284 for the ODI). The median rate of increase was 7.5 (5 to 10) mm/year in the AHI greater than 30 events/h group and 5.0 (0 to 8) mm/year in the ODI greater than 30 events/h group. With regard to blood pressure control, the diastolic blood pressure varied as function of the ODI category (p = 0.0074). CONCLUSIONS: Our results suggest that systematic screening for post-ASS OSAS is of value. The false lumen dilatation rate appears to be related to the severity of OSAS. It remains to be seen whether treatment of OSAS would modify the false lumen dilatation rate. PMID- 27262917 TI - Transmission Dynamics of Rhodesian Sleeping Sickness at the Interface of Wildlife and Livestock Areas. AB - Many wilderness areas of East and Southern Africa are foci for Rhodesian sleeping sickness, a fatal zoonotic disease caused by trypanosomes transmitted by tsetse flies. Although transmission in these foci is traditionally driven by wildlife reservoirs, rising human and livestock populations may increase the role of livestock in transmission cycles. Deciphering transmission dynamics at wildlife and livestock interface areas is key to developing appropriate control. Data are lacking for key parameters, including host distributions, tsetse density, and mortality rates, and the relative roles of livestock and wildlife as hosts in fragmented habitats, limiting the development of meaningful models to assist in the assessment and implementation of control strategies. PMID- 27262919 TI - Monique Capron: Science, Strength, and Elegance. PMID- 27262916 TI - Incidence and Risk Factors Related to Symptomatic Venous Thromboembolic Events After Esophagectomy for Cancer. AB - BACKGROUND: Major oncologic surgery is associated with a high incidence of venous thromboembolic events (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE). However, the incidence and risk factors for symptomatic VTE during curative treatment for patients with esophageal cancer are poorly documented. METHODS: Data were collected from 30 European centers from 2000 to 2010. The incidence of in-hospital VTE was assessed in 2,944 patients with esophageal cancer having surgery with curative intent, and 50 clinically relevant parameters were assessed as potential risk factors for VTE. Patients received low molecular weight heparin prophylaxis during hospital stay and for 4 weeks after surgery. RESULTS: Eighty-four patients (2.9%) developed a symptomatic VTE; all of them had a DVT and 44 were also diagnosed with a PE. In the VTE group there were 19 postoperative deaths recorded, 5 of which (26.3%) were directly caused by PE at postoperative days 7, 10, 21, 45, and 48 despite VTE prophylaxis. In-hospital postoperative mortality was significantly higher in VTE patients (23% versus 7%, p < 0.001) and mean hospital stay was also longer in this group (33 +/- 24 versus 25 +/- 21 days, p < 0.001). Multivariable analysis showed that high American Society of Anesthesiologists (ASA) class (p = 0.008), pneumopathy (p = 0.002), or an acute respiratory distress syndrome (ARDS) (p = 0.015) were significantly associated with VTE. CONCLUSIONS: Patients with ASA class III or IV and those who present a postoperative pneumopathy or ARDS seem to be at higher risk for VTE. Thus, current VTE screening and thromboprophylaxis for these patients might be inadequate and needs further investigation. PMID- 27262918 TI - Eosinophils in Helminth Infection: Defenders and Dupes. AB - Eosinophilia is a central feature of the host response to helminth infection. Larval stages of parasitic worms are killed in vitro by eosinophils in the presence of specific antibodies or complement. These findings established host defense as the paradigm for eosinophil function. Recently, studies in eosinophil ablated mouse strains have revealed an expanded repertoire of immunoregulatory functions for this cell. Other reports document crucial roles for eosinophils in tissue homeostasis and metabolism, processes that are central to the establishment and maintenance of parasitic worms in their hosts. In this review, we summarize current understanding of the significance of eosinophils at the host parasite interface, highlighting their distinct functions during primary and secondary exposure. PMID- 27262920 TI - Relationship between knee osteoarthritis and the locomotive syndrome risk tests: A cross-sectional study. AB - OBJECTIVE: To determine the relationship between locomotive syndrome (LS) risk tests and knee osteoarthritis (KOA). STUDY DESIGN: Cross-sectional cohort study. METHODS: In 2015, 225 people (male 84, females 141, mean age 67.9, range 30-90) were examined using LS risk tests, including the stand-up test, the two-step test, and the 25-question risk assessment, in Katashina Village in Gunma prefecture. The Japanese orthopaedic association defined LS risk test stage 1, difficulty with standing from a 40-cm-high seat using one-leg in the stand-up test, two-step test <1.3, the 25-question risk assessment ?7, and defined stage 2, difficulty with standing from a 20-cm-high seat using both legs in the stand up test, two-step test <1.1, the 25-question risk assessment ?16. Persons with two or more of the following on the ultrasound (US) assessment were defined as having KOA: peripheral joint space (PJS) < 5 mm during weight-bearing; medial radial displacement (MRD) > 5 mm during weight-bearing; and osteophytes > 2 mm. If the residents had KOA in either knee, they were defined as having KOA. RESULTS: 45 residents had KOA in either knee. Logistic regression analysis adjusted for age, height, weight, gender, and knee pain was performed with stage 0 as reference. On the stand-up test, the odds ratio was 5.484 (95% confidence interval (CI) 1.966-15.297) for stage 1 and 2.067 (95% CI 0.426-10.017) for stage 2. On the two-step test, the odds ratio was 1.497 (95% CI 0.557-4.021) for stage 1 and 0.71 (95% CI 0.210-2.395) for stage 2. On the 25-question risk assessment, the odds ratio was 1.73 (95% CI 0.646-4.631) for stage 1 and 1.5 (95% CI 0.508 4.433) for stage 2. CONCLUSIONS: A stand-up test of stage 1 had a significant relationship with KOA. This might suggest that proper care of KOA is needed to prevent progressive disability. PMID- 27262921 TI - Delivering RapidArc(r): A comprehensive study on accuracy and long term stability. AB - PURPOSE: To establish the reliability and accuracy of a UNIQUE Linac in delivering RapidArc treatments and assess its long term stability. MATERIALS AND METHODS: UNIQUE performance was monitored and analyzed for a period of nearly two years. 2280 Dynalog files, related to 179 clinical RapidArc treatments were collected. Different tumor sites and dose scheduling were included, covering the full range of our treatment plans. Statistical distributions of MLC motion error, gantry rotation error and MU delivery error were evaluated. The stochastic and systematic nature of each error was investigated together with their variation in time. RESULTS: All the delivery errors are found to be small and more stringent tolerances than those proposed by TG142 are suggested. Unlike MLC positional errors, where a linear relationship with leaf speed holds, other Volumetric Modulated Arc Therapy (VMAT) parameters reveal a random nature and, consequently, a reduced clinical relevance. MLC errors are linearly related only to leaf speed no matter the shape of the MLC apertures. Gantry rotation and MU delivery are as accurate as major competing Linacs. UNIQUE was found to be reliable and accurate throughout the investigation period, regardless of the specific tumor sites and fractionation schemes. CONCLUSIONS: The accuracy of RapidArc treatments delivered with UNIQUE has been established. The stochastic nature of delivery errors is proven. Long term statistics of the delivery parameter errors do not show significant variations, confirming the reliability of the VMAT delivery system. PMID- 27262922 TI - Functionalized graphene nanocomposites for enhancing photothermal therapy in tumor treatment. AB - Graphene and its derivatives have unique physical and chemical properties that make them promising vehicles for photothermal therapy (PTT)-based cancer treatment. With intrinsic near-infrared (NIR) absorption properties, graphene based nanomaterials can be used for PTT and other therapeutics, particularly in combination therapy, to provide successful thermal ablation of cancer cells. In the recent years, advances in graphene-based PTT have produced efficient and efficacious tumor inhibition via nanomaterial structural design and different functionalizations of graphene-derived nanocomposites. Graphene-based nanosystems exhibit multifunctional properties that are useful for PTT applications including enhancement of multimodalities, guided imaging, enhanced chemotherapy and low power efficient PTT for optimum therapeutic efficiency. Therefore, in this review, we address critical issues and future aspects of PTT-based combination therapy. PMID- 27262923 TI - Radiation effects on the tumor microenvironment: Implications for nanomedicine delivery. AB - The tumor microenvironment has an important influence on cancer biological and clinical behavior and radiation treatment (RT) response. However, RT also influences the tumor microenvironment in a complex and dynamic manner that can either reinforce or inhibit this response and the likelihood of long-term disease control in patients. It is increasingly evident that the interplay between RT and the tumor microenvironment can be exploited to enhance the accumulation and intra tumoral distribution of nanoparticles, mediated by changes to the vasculature and stroma with secondary effects on hypoxia, interstitial fluid pressure (IFP), solid tissue pressure (STP), and the recruitment and activation of bone marrow derived myeloid cells (BMDCs). The use of RT to modulate nanoparticle drug delivery offers an exciting opportunity to improve antitumor efficacy. This review explores the interplay between RT and the tumor microenvironment, and the integrated effects on nanoparticle drug delivery and efficacy. PMID- 27262926 TI - Recent advances in degradable lactide-based shape-memory polymers. AB - Biodegradable polymers are versatile polymeric materials that have a high potential in biomedical applications avoiding subsequent surgeries to remove, for example, an implanted device. In the past decade, significant advances have been achieved with poly(lactide acid) (PLA)-based materials, as they can be equipped with an additional functionality, that is, a shape-memory effect (SME). Shape memory polymers (SMPs) can switch their shape in a predefined manner upon application of a specific external stimulus. Accordingly, SMPs have a high potential for applications ranging from electronic engineering, textiles, aerospace, and energy to biomedical and drug delivery fields based on the perspectives of new capabilities arising with such materials in biomedicine. This study summarizes the progress in SMPs with a particular focus on PLA, illustrates the design of suitable homo- and copolymer structures as well as the link between the (co)polymer structure and switching functionality, and describes recent advantages in the implementation of novel switching phenomena into SMP technology. PMID- 27262924 TI - Advances in biosensing strategies for HIV-1 detection, diagnosis, and therapeutic monitoring. AB - HIV-1 is a major global epidemic that requires sophisticated clinical management. There have been remarkable efforts to develop new strategies for detecting and treating HIV-1, as it has been challenging to translate them into resource limited settings. Significant research efforts have been recently devoted to developing point-of-care (POC) diagnostics that can monitor HIV-1 viral load with high sensitivity by leveraging micro- and nano-scale technologies. These POC devices can be applied to monitoring of antiretroviral therapy, during mother-to child transmission, and identification of latent HIV-1 reservoirs. In this review, we discuss current challenges in HIV-1 diagnosis and therapy in resource limited settings and present emerging technologies that aim to address these challenges using innovative solutions. PMID- 27262925 TI - PLA micro- and nano-particles. AB - Poly(d,l-lactic acid) (PLA) has been widely used for various biomedical applications for its biodegradable, biocompatible, and nontoxic properties. Various methods, such as emulsion, salting out, and precipitation, have been used to make better PLA micro- and nano-particle formulations. They are widely used as controlled drug delivery systems of therapeutic molecules, including proteins, genes, vaccines, and anticancer drugs. Even though PLA-based particles have challenges to overcome, such as low drug loading capacity, low encapsulation efficiency, and terminal sterilization, continuous innovations in particulate formulations will lead to development of clinically useful formulations. PMID- 27262928 TI - HLA-G coding region and 3'untranslated region (3'UTR) in two Chinese Han populations. AB - In this study, exons 2-4 and 3'untranslated region (3'UTR) of human leukocyte antigen (HLA)-G gene were investigated for 201 and 104 healthy unrelated Han samples recruited from Hunan Province, southern China and central Inner Mongolia Autonomous Region, northern China, respectively, using sequence-based typing and cloning methods. Totally 12 HLA-G alleles in the coding region, 9 variable sites in 3'UTR, 8 3'UTR haplotypes and 15 HLA-G extended haplotypes (EHs) incorporating the coding region and 3'UTR were observed. Very strong linkage disequilibrium (LD) was observed between HLA-A and HLA-G, and between HLA-G coding region and 3'UTR in each population (all global P=0.0000). Seven HLA-A-G haplotypes showed significant LD in both populations. Three HLA-G alleles in the coding region, 4 polymorphic sites in the 3'UTR, 3 3'UTR haplotypes and 4 HLA-G EHs differed significantly in their distributions between the 2 Chinese Han populations (all P<=0.0001). There was evidence for balancing selection acting on HLA-G 3'UTR positions +3010, +3142 and +3187 in the two populations. The NJ dendrograms demonstrated the existence of two basic HLA-G lineages and indicated that, HLA G*01:01:01, the most common HLA-G allele, formed a separate lineage from other alleles. Our results shed new lights into HLA-G genetics among Chinese Han populations. The findings reported here are of importance for future studies related to post-transcriptional regulation of HLA-G allelic expression and the potential role of HLA-G in disease association in populations of Chinese ancestry. PMID- 27262927 TI - Fine-tuning neutrophil activation: Strategies and consequences. AB - In spite of their important role in host defense, neutrophils can also cause severe morbidity and mortality. Neutrophils have an extensive armory necessary to eradicate pathogens, but neutrophil infiltration and activation also induces major tissue injury associated with acute and chronic inflammatory disorders. Here, we review neutrophil anti-microbial functions and discuss their individual contribution to disease pathogenesis. Furthermore, we provide an overview of the anti-inflammatory drugs that can dampen neutrophil transmigration, elastase activity, and the production of reactive oxygen species which are already in clinical trials. The discovery of potential inhibitors of the release of neutrophil extracellular trap is still in its infancy. Here, we discuss small molecule inhibitors and inhibitory receptors that show promising results in reducing neutrophil extracellular trap formation in vitro and in vivo and discuss the advantages and drawbacks of inhibiting the release of neutrophil extracellular traps as a therapeutic treatment. Specific suppression of neutrophil extracellular trap formation, preferably while other antimicrobial functions are preserved, would be an ideal approach to treat neutrophilic inflammation, since it prevents acute as well as chronic neutrophil-associated pathology. PMID- 27262929 TI - Chemokine genetic polymorphism in human health and disease. AB - Chemokine receptor-ligand interaction regulates transmigration of lymphocytes and monocytes from circulation to the inflammatory sites. CC chemokine receptors, chemokine receptor 2(CCR2) and 5 (CCR5) are important in recruitment of immune cells as well as non-immune cells under pathological condition. CCR2, CCR5 and their ligands (CCL2 and CCL5) are major contributor to the autoimmune and inflammatory diseases and cancer. Currently studies are being done to explore genetic variations in chemokine genes and their involvement in diseases that could make clear disease severity and deaths. Conflicting results of studies in different populations and diseases promoted to investigate chemokines genetic polymorphisms in miscellaneous diseases. This study is aimed to evaluate the influence of chemokines genetic polymorphisms in pathogenesis and outcome of prevalent non infectious diseases. Present study demonstrates the likely role played by genetic variations in drug response and evolution. Moreover this study highlights chemokine as therapeutic target and diagnostic biomarker in pathological condition. PMID- 27262930 TI - A reduced population of CD103(+)CD11b(+) dendritic cells has a limited impact on oral Salmonella infection. AB - CD103(+)CD11b(+) dendritic cells (DC) are the major migratory DC subset in the small intestine lamina propria (siLP) and their survival is dependent on the transcription factor interferon regulatory factor 4 (IRF4). Mice with a DC specific deletion of irf4 (CD11c-cre.Irf4 mice) have reduced mucosal CD103(+)CD11b(+) DC and altered T cell differentiation to protein antigen. The influence of CD103(+)CD11b(+) DC on oral infection with the gastrointestinal pathogen Salmonella, however, is poorly understood and is investigated here. We show that, despite being infected with Salmonella, CD11c-cre.Irf4 mice (called Cre(+) mice) conserve the reduction in CD103(+)CD11b(+) DC observed in naive Cre(+) mice, particularly in the mesenteric lymph nodes (MLN) but also in the siLP at day 3 post infection. Moreover, Salmonella-infected Cre(+) mice have a similar bacterial burden in intestinal tissues (siLP, MLN and Peyer's patches) as well as the spleen compared to infected Cre(-) controls. The T cell compartment, including the frequency of IFN-gamma and IL-17-producing T cells, is not altered in intestinal tissues of Salmonella-infected Cre(+) mice relative to infected Cre(-) controls. In addition, no difference between infected Cre(+) and Cre(-) mice was observed in either the concentration of IL-6 or IL-17 in whole tissue lysates of siLP, MLN or Peyer's patches or in the serum concentration of Salmonella-specific IgG and IgM. Overall the data suggest that the reduction of CD103(+)CD11b(+) DC in Cre(+) mice has little if any impact on Salmonella burden in infected tissues or eliciting effector functions important in host survival at later stages of the infection. PMID- 27262931 TI - Gender differences in burns: A study from emergency centres in the Western Cape, South Africa. AB - INTRODUCTION: Little is known about gender differences in aetiology and management of acute burns in resource-constrained settings in South Africa. METHOD: This cross-sectional study is based on burn case reports (n=1915) from eight emergency centres in Western Cape, South Africa (June 2012-May 2013). Male/female rate ratios by age group and age-specific incidence rates were compiled for urban and rural areas along with gender differences in proportions between children and adults for injury aetiology, burn severity, length of stay and patient disposition. RESULTS: Children 0-4 years in urban areas had the highest burn incidence but only among adults did male rates surpass females, with fire burns more common among men 20-39 years and hot liquid burns among men 55+ years. Men had a higher proportion of burns during weekends, from interpersonal violence and suspected use of alcohol/other substances, with more pronounced differences for hot liquid burns. Despite similar Abbreviated Injury Scale (AIS) scores, men were more often transferred to higher levels of care and women more often treated and discharged. CONCLUSION: Burns were far more common among children although gender differences arose only among adults. Men sustained more injuries of somewhat different aetiology and were referred to higher levels of care more often for comparable wound severity. The results suggest different disposition between men and women despite similar AIS scores. However, further studies with more comprehensive information on severity level and other care- and patient-related factors are needed to explore these results further. PMID- 27262932 TI - Response of heterogeneous cancer cells on targeted nanoparticles. AB - Heterogenous cancer cells possess cancer multidrug resistance (MDR) due to their relative quiescence and ABC-transporter expression. Heterogenous cancer cells can be detected by an Rh123 exclusion assay for identifying Rh123low population. In the present study, we fabricated targeted nanoparticles entrapped with Rh123 (Rh123 NPs) to investigate the effect of these targeted nanoparticles on an Rh123low population. The Rh123low population stained by Rh123 NPs exhibited similar heterogeneity to that stained by Rh123. In addition, the ABC-transporters did not contribute to the uptake of Rh123 or Rh123 NPs. Interestingly, ABC transporters in the Rh123low population stained by Rh123 were possibly responsible for Rh123 efflux, while Rh123 NPs were not susceptible to ABC transporters in the Rh123low population. It is plausible that the synergistic effect of NPs caused a targeted and endocytic effect which promoted the cellular uptake of Rh123 NPs, and the targeted effect played a more important role. PMID- 27262934 TI - Suicidal ideation and suicide attempts among youth who report bully victimization, bully perpetration and/or low social connectedness. AB - The current study examined characteristics of bullying involvement and social connectedness in relation to suicide ideation and attempts in a sample of youth who report bully victimization, bully perpetration, and/or low social connectedness. The sample was comprised of 321 youth (67% female), ages 12-15 years (M = 13.6), recruited from an emergency department in the Midwest region of the United States. Results indicated that lower levels of social connectedness and higher levels of bully victimization and perpetration were significantly associated with suicide ideation and attempts. Level of social connectedness did not moderate the relationship between bullying involvement and suicide risk. The associations between the severity of subtypes of bully victimization and perpetration (verbal, relational, physical), electronic bullying involvement, and suicide risk were examined. Results highlight a continuum in severity of bullying involvement and social connectedness associated with suicide risk. Implications of these results are discussed. PMID- 27262933 TI - Restoring the oncosuppressor activity of microRNA-34a in glioblastoma using a polyglycerol-based polyplex. AB - Glioblastoma multiforme (GBM) is the most common and aggressive primary neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness, and drug resistance. microRNA-based therapeutics represent a promising approach due to their ability to inhibit multiple targets. In this work, we aim to restore the oncosuppressor activity of microRNA-34a (miR-34a) in GBM. We developed a cationic carrier system, dendritic polyglycerolamine (dPG NH2), which remarkably improves miRNA stability, intracellular trafficking, and activity. dPG-NH2 carrying mature miR-34a targets C-MET, CDK6, Notch1 and BCL-2, consequently inhibiting cell cycle progression, proliferation and migration of GBM cells. Following complexation with dPG-NH2, miRNA is stable in plasma and able to cross the blood-brain barrier. We further show inhibition of tumor growth following treatment with dPG-NH2-miR-34a in a human glioblastoma mouse model. We hereby present a promising technology using dPG-NH2-miR-34a polyplex for brain tumor treatment, with enhanced efficacy and no apparent signs of toxicity. PMID- 27262935 TI - [Bile salt nephropathy/cholemic nephrosis]. AB - Bile cast nephropathy is a tubulo-interstitial nephropathy. Its diagnosis may be under-estimated. It develops in patients who have cholestatic jaundice, with high bilirubinemia. Bile salts are freely filtered through glomerulus. Under certain circumstances, it forms casts into the tubule and cause an acute tubular necrosis. The diagnosis evidence is histologic, but fulfilment of renal biopsy is often made difficult, because of the hemostatic abnormalities that patients with hepatocellular injury develop. The treatment is supportive and etiological. We report here the case of a patient who presented a drug-induced hepatic jaundice, complicated with acute kidney failure secondary to bile cast nephropathy. We present the histological diagnosis evidence. PMID- 27262936 TI - The synthetic gestagen levonorgestrel directly affects gene expression in thyroid and pituitary glands of Xenopus laevis tadpoles. AB - The synthetic gestagen levonorgestrel (LNG) was previously shown to perturb thyroid hormone-dependent metamorphosis in Xenopus laevis. However, so far the mechanisms underlying the anti-metamorphic effects of LNG remained unknown. Therefore, a series of in vivo and ex vivo experiments was performed to identify potential target sites of LNG action along the pituitary-thyroid axis of X. laevis tadpoles. Prometamorphic tadpoles were treated in vivo with LNG (0.01 10nM) for 72h and brain-pituitary and thyroid tissue was analyzed for marker gene expression. While no treatment-related changes were observed in brain-pituitary tissue, LNG treatment readily affected thyroidal gene expression in tadpoles including decreased slc5a5 and iyd mRNA expression and a strong induction of dio2 and dio3 expression. When using an ex vivo organ explant culture approach, direct effects of LNG on both pituitary and thyroid gland gene expression were detecTable Specifically, treatment of pituitary explants with 10nM LNG strongly stimulated dio2 expression and concurrently suppressed tshb expression. In thyroid glands, ex vivo LNG treatment induced dio2 and dio3 mRNA expression in a thyrotropin-independent manner. When thyroid explants were cultured in thyrotropin-containing media, LNG caused similar gene expression changes as seen after 72h in vivo treatment including a very strong repression of thyrotropin induced slc5a5 expression. Concerning the anti-thyroidal activity of LNG as seen under in vivo conditions, our ex vivo data provide clear evidence that LNG directly affects expression of genes important for thyroidal iodide handling as well as genes involved in negative feedback regulation of pituitary tshb expression. PMID- 27262938 TI - Response of AMP-activated protein kinase and energy metabolism to acute nitrite exposure in the Nile tilapia Oreochromis niloticus. AB - Adenosine monophosphate-activated protein kinase (AMPK) is a prevalent mammalian energy metabolism sensor, but little is known about its role as an energy sensor in fish experiencing stress. We aimed to study AMPK in Oreochromis niloticus on both the molecular and the physical level. We found that the cDNAs encoding the AMPKalpha1 and AMPKalpha2 variants of the O. niloticus catalytic alpha subunit were 1753bp and 2563 bp long and encoded 571 and 557 amino acids, respectively. Both the AMPKalpha1 and the AMPKalpha2 isoform possess structural features similar to mammalian AMPKalpha, including a phosphorylation site at Thr172 in the N-terminus, and exhibit high homology with other fish and vertebrate AMPKalpha sequences (81.3%-98.1%). mRNA encoding the AMPKalpha isoforms was widely expressed in various tissues with distinctive patterns. AMPKalpha1 and AMPKalpha2 were primarily expressed in the intestines and brain, respectively. Under acute nitrite challenge, the mRNA encoding the AMPKalpha isoforms, as well as AMPK activity, changed over time. Its recovery period in freshwater, combined with the fact that it is highly conserved, suggests that fish AMPK, like its mammalian orthologues, acts as an energy metabolism sensor. Furthermore, subsequent decreases in AMPK mRNA levels and activity suggested that its action was transient but efficient. Physically, glucose, lactic acid and TGs in plasma, as well as energy materials in the hepatopancreas and muscle, were significantly altered over time, indicating changes in energy metabolism during the experimental period. These data have enabled us to characterize energy utilization in O. niloticus and further illustrate the role of fish AMPK as an energy sensor. This study provides new insight into energy metabolism and sensing by AMPK in teleost and necessitates further study of the multiple physiologic roles of AMPK in fish. PMID- 27262937 TI - AHR-related activities in a creosote-adapted population of adult atlantic killifish, Fundulus heteroclitus, two decades post-EPA superfund status at the Atlantic Wood Site, Portsmouth, VA USA. AB - Atlantic killifish, Fundulus heteroclitus, are adapted to creosote-based PAHs at the US EPA Superfund site known as Atlantic Wood (AW) on the southern branch of the Elizabeth River, VA USA. Subsequent to the discovery of the AW population in the early 1990s, these fish were shown to be recalcitrant to CYP1A induction by PAHs under experimental conditions, and even to the time of this study, killifish embryos collected from the AW site are resistant to developmental deformities typically associated with exposure to PAHs in reference fish. Historically, however, 90 +% of the adult killifish at this site have proliferative hepatic lesions including cancer of varying severity. Several PAHs at this site are known to be ligands for the aryl hydrocarbon receptor (AHR). In this study, AHR-related activities in AW fish collected between 2011 and 2013 were re-examined nearly 2 decades after first discovery. This study shows that CYP1A mRNA expression is three-fold higher in intestines of AW killifish compared to a reference population. Using immunohistochemistry, CYP1A staining in intestines was uniformly positive compared to negative staining in reference fish. Livers of AW killifish were examined by IHC to show that CYP1A and AHR2 protein expression reflect lesions-specific patterns, probably representing differences in intrinsic cellular physiology of the spectrum of proliferative lesions comprising the hepatocarcinogenic process. We also found that COX2 mRNA expression levels were higher in AW fish livers compared to those in the reference population, suggesting a state of chronic inflammation. Overall, these findings suggest that adult AW fish are responsive to AHR signaling, and do express CYP1A and AHR2 proteins in intestines at a level above what was observed in the reference population. PMID- 27262939 TI - Lethal and sub-lethal effects on the Asian common toad Duttaphrynus melanostictus from exposure to hexavalent chromium. AB - Chromium discharged in industrial effluents frequently occurs as an environmental pollutant, but the lethal and sub-lethal effects the heavy metal might cause in animals exposed to it have been insufficiently investigated. Selecting the amphibian Duttaphrynus melanostictus, we carried out laboratory tests to investigate the effects of short and long term exposure to hexavalent chromium (Cr(VI)) in both tadpoles and adult toads. The concentrations used were 0.002, 0.02, 0.2, 1.0 and 2.0mg/L, the first three corresponding to field levels. In vitro exposures were also carried out using toad erythrocytes and Cr(VI) concentrations of 0.0015, 0.003, 0.015, 0.03, 0.15mg/L. Mortality, growth retardation, developmental delays and structural aberrations were noted in the metal-treated tadpoles, with increasing incidence corresponding to increase in Cr(VI) level and duration of exposure. Many of the sub-lethal effects were evident with long term exposure to environmentally relevant levels of the toxicant. Changes in selected blood parameters and erythrocyte morphometry were also detected in Cr(VI) exposed toads, indicating anaemic and leucopenic conditions. In the genotoxicity study, DNA damage indicated by comet assay and increased micronuclei frequency, occurred at the low Cr(VI) concentrations tested. The multiple deleterious effects of exposure to chromium signal the need for monitoring and controlling the discharge of chromium to the environment. The dose-dependency and genotoxic effects observed in this widely distributed Asian toad indicates its suitability for monitoring heavy metal pollution in aquatic systems. PMID- 27262940 TI - Comparison of stillbirth rates by cause among Haitians and non-Haitians in Canada. AB - OBJECTIVE: To compare rates of stillbirth among Haitians and non-Haitians in Canada. METHODS: A retrospective cohort study was performed using data on all stillborn and live-born singletons weighing at least 500 g in the province of Quebec, Canada, from 1981 to 2010. Stillbirth rates were computed, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for Haitians relative to non-Haitians. The main outcome measure was stillbirth by cause of death. RESULTS: Data for 9657 stillbirths (124 Haitian) and 2 414 751 live births (17 165 Haitian) were included. Stillbirth rates were higher for Haitians than non-Haitians (7.17 [95% CI 5.91-8.43] vs 3.96 [95% CI 3.88-4.04] per 1000 births), particularly for cord prolapse (adjusted HR 1.87, 95% CI 1.10-3.18) and placental abruption (adjusted HR 2.84, 95% CI 1.95-4.15). Haitians had higher risks of stillbirth due to cord prolapse and abruption at every week of pregnancy. Risks were not elevated for stillbirth due to congenital anomaly, a cause less responsive to urgent intervention. CONCLUSION: Stillbirth rates among Haitians are disproportionately high in Canada, particularly fetal death due to cord prolapse and placental abruption. The potential to reduce stillbirth rates through optimal emergency care in vulnerable minorities requires further investigation. PMID- 27262941 TI - Retention of skills 2 years after completion of a postpartum hemorrhage simulation training program in rural Rwanda. AB - OBJECTIVE: To evaluate the long-term retention of skills gained by rural physicians who completed a postpartum hemorrhage simulation-training program. METHODS: A quasi-experimental pre-post intervention study enrolled a convenience sample of generalist physicians in rural Rwanda. Participants underwent initial simulation training including pre- and post-training testing in February 2012. Simulation drills to assess skill retention were conducted in March 2014. Participants were scored based on their communication, evaluation, and management skills. Median scores and inter-quartile ranges were calculated and the Wilcoxon signed-rank sum test was used to compare the pre-training, post-training, and retention scores. Physician confidence was assessed using a survey. RESULTS: In total, 11 physicians were enrolled; eight were available for the 2-year skill retention evaluation. Significant improvements were observed when comparing participants' pre-training and post-training communication (P=0.03), evaluation (P=0.05), and management (P=0.02) scores, and there were no changes between participants' post-training and 2-year communication (P>0.99), evaluation (P=0.16), and management (P=0.46) scores. There were no differences in the self reported confidence measures across the duration of the study. CONCLUSION: Simulation training is an effective method for teaching postpartum hemorrhage management skills to generalist physicians in rural areas and skills are retained for at least 2 years. Further studies could determine the optimal time intervals for refresher training. PMID- 27262942 TI - Validation of specific questionnaires to assess nausea and vomiting of pregnancy in a French population. AB - OBJECTIVE: To validate the modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score and the Health-Related Quality of Life for Nausea and Vomiting of Pregnancy (NVP-QOL) score in a French population. METHODS: A retrospective study was conducted of data for women who delivered at a tertiary care hospital in La Roche sur Yon, France, between November 1, 2012, and April 1, 2013. Only women who reported nausea and vomiting of pregnancy (NVP) in the first trimester were invited to respond to the two questionnaires. RESULTS: Overall, complete questionnaires were available from 399 women, 238 (59.6%) of whom reported NVP in the first trimester. The modified-PUQE score was associated with the self-reported symptom severity (P<0.001). A relationship was also noted when either the NVP-QOL score or the modified-PUQE score was compared with the symptom intensity (P<0.001 for both comparisons). Furthermore, a high NVP-QOL score was associated with a high modified-PUQE score (P<0.001). CONCLUSION: The modified PUQE and NVP-QOL scores provided valid indices for assessing NVP severity and alterations in quality of life. Owing to its simplicity, the modified-PUQE score might be used routinely among women experiencing NVP in the first trimester of pregnancy. PMID- 27262943 TI - A comparison of plants and animals in their responses to risk of consumption. AB - Both plants and animals reduce their risk of being eaten by detecting and responding to herbivore and predator cues. Plants tend to be less mobile and rely on more local information perceived with widely dispersed and redundant tissues. As such, plants can more easily multi-task. Plants are more tolerant of damage and use damage to their own tissues as reliable cues of risk; plants have a higher threshold before responding to the threat of herbivory. Plants also use diverse cues that include fragments of plant tissue and molecular patterns from herbivores, herbivore feeding, or microbial associates of herbivores. Instead of fleeing from attackers, plants reallocate valuable resources to organs at less risk. They minimize unnecessary defenses against unrealized risks and costs of failing to defend against actual risk. Plants can remember and learn, although these abilities are poorly understood. PMID- 27262944 TI - Complete genome sequence of a new bipartite begomovirus infecting fluted pumpkin (Telfairia occidentalis) plants in Cameroon. AB - The complete genome sequence was determined and characterized for a previously unreported bipartite begomovirus from fluted pumpkin (Telfairia occidentalis, family Cucurbitaceae) plants displaying mosaic symptoms in Cameroon. The DNA-A and DNA-B components were ~2.7 kb and ~2.6 kb in size, and the arrangement of viral coding regions on the genomic components was like those characteristic of other known bipartite begomoviruses originating in the Old World. While the DNA-A component was more closely related to that of chayote yellow mosaic virus (ChaYMV), at 78 %, the DNA-B component was more closely related to that of soybean chlorotic blotch virus (SbCBV), at 64 %. This newly discovered bipartite Old World virus is herein named telfairia mosaic virus (TelMV). PMID- 27262945 TI - Profile of expression of certain markers of apoptosis in chronic hepatitis C and hepatitis B patients in an Egyptian population. AB - Increased peripheral blood mononuclear cell (PBMC) apoptosis during viral hepatitis has been suggested to cause impaired regulation of the immune response and maintenance of the infection. The purpose of this work was to study the expression of some apoptotic markers in chronic hepatitis B (CHB) and C (CHC) infections in order to understand the underlying mechanisms of immune failure and viral persistence. This study aims to evaluate the level of PBMC apoptosis and the expression of the apoptosis-related proteins Fas and Bcl-2 in CHB and CHC patients. This case control study was carried out on 38 cases (group I: 20 chronic HCV patients; group II: 18 chronic HBV patients) attending the Tropical Medicine Clinic, Mansoura University Hospital, in addition to 10 healthy controls. Morphological assessment of apoptosis of cultured PBMCs was done. The level of Fas and Bcl-2 expression by PBMCs was detected using flow cytometry. An increased level of apoptosis correlated with increased Fas expression, but no increase in Bcl-2 expression was found on the surface of PBMCs in CHC and CHB patients compared to controls. No significant difference in the level of apoptosis, Fas, or Bcl2 expression between CHC and CHB patients was detected. Modulation of apoptosis, particularly by manipulation of Fas receptor activation, may be of therapeutic benefit in chronic CHB and CHC. PMID- 27262946 TI - Genipin alleviates LPS-induced acute lung injury by inhibiting NF-kappaB and NLRP3 signaling pathways. AB - Genipin has been reported to have anti-inflammatory effect. However, its role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored. This study aimed to evaluate the effect of genipin on murine model of acute lung injury induced by LPS. The mice were treated with genipin 1h before LPS administration. 12h later, the myeloperoxidase (MPO) in lung tissues and lung wet/dry ratio were detected. The levels of TNF-alpha, IL-1beta and IL-6 in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Apart from this, we use western blot to detect the protein expression in the NF-kappaB and NLRP3 signaling pathways. The results showed that the treatment of genipin markedly attenuated the lung wet/dry ratio and the MPO activity. Moreover, it also inhibited the levels of TNF-alpha, IL-1beta, IL-6 in the BALF. In addition, genipin significantly inhibited LPS-induced NF-kappaB and NLRP3 activation. In conclusion, these results demonstrate that genipin protected against LPS-induced ALI through inhibiting NF-kappaB and NLRP3 signaling pathways. PMID- 27262947 TI - Proteomic analysis of Mortierella isabellina M6-22 during cold stress. AB - We aimed to gain a better understanding of cold adaption in Mortierella isabellina M6-22 by using proteomics approaches. The temperature range and optimal temperature for M6-22 growth were investigated, and composition changes in fatty acids were analyzed. Accompanied with the 2-D gel electrophoresis, MALDI TOF/TOF-MS analysis was conducted to characterize alterations in protein profiling in M6-22 cultured at 30 degrees C for 24 h and 15 degrees C for another 24 h when compared with those cultured at 30 degrees C for 48 h. Gene Ontology (GO) cluster analysis was finally conducted for successfully identified proteins. M6-22 cells could grow well at temperatures ranging from 15 to 30 degrees C. As temperature decreased from 30 to 15 degrees C, LA and GLA significantly increased from 11.63 to 17.85 % and from 9.12 to 13.19 %, respectively, while oleic acid significantly decreased from 47.25 to 36.53 %. Proteomics analyses revealed 111 differentially expressed protein spots, among which 5 unique proteins (A38, A40, A47, A49 and A58), 29 up-regulated proteins and 10 down-regulated proteins were identified by MALDI-TOF/TOF-MS. GO enrichment analysis demonstrated that these proteins mainly involved in glycolytic pathway (A34 and A50), electron transport (A28), ATP production (A35 and B39) and protein modification (A38). A total of 44 differentially expressed proteins have been successfully identified in M. isabellina M6-22 cultured at 15 degrees C. These proteins may play important roles in cold adaption via regulation of ATP synthesis, activation of cold-adaptive proteins, degradation of needless protein, accumulation of PUFAs, etc. PMID- 27262949 TI - The dynamic changes of X chromosome inactivation during early culture of human embryonic stem cells. AB - X chromosome inactivation (XCI) is required for dosage compensation of X-linked genes in human female cells. Several previous reports have described the promiscuous XCI status in long-term cultured female human embryonic stem cells (hESCs), and the majority of them exhibit non-random XCI. However, when and how such female hESCs acquire the aberrant XCI states during culture is unknown. Herein, through comparing the XCI states in 18 paired hES cell lines throughout early culture, we revealed a uniform dynamic change during this culture period under a widely used culture condition. The female initial hESCs (ihESCs, P4-P9) expressed XIST RNA, H3K27me3 punctate enrichment and displayed random XCI pattern. By further culturing, the female early hESCs (ehESCs, P20-P30) lost the expression of XIST RNA, H3K27me3 punctate enrichment and exhibited a completely skewed XCI pattern. Importantly, a subset of X-linked genes was up-regulated in ehESCs, including some cancer-related genes. At last, we found 5% physiological oxygen was beneficial for the expression of XIST and H3K27me3 punctate enrichment, but not for the XCI pattern. We conclude that the XCI dynamic change is a frequent epigenetic instability event during early culture, which is accompanied by the up-regulation of some X-linked genes. Furthermore, we emphasize that physiological oxygen is beneficial for XCI fidelity. PMID- 27262948 TI - The role of Proteus mirabilis cell wall features in biofilm formation. AB - Biofilms formed by Proteus mirabilis strains are a serious medical problem, especially in the case of urinary tract infections. Early stages of biofilm formation, such as reversible and irreversible adhesion, are essential for bacteria to form biofilm and avoid eradication by antibiotic therapy. Adhesion to solid surfaces is a complex process where numerous factors play a role, where hydrophobic and electrostatic interactions with solid surface seem to be substantial. Cell surface hydrophobicity and electrokinetic potential of bacterial cells depend on their surface composition and structure, where lipopolysaccharide, in Gram-negative bacteria, is prevailing. Our studies focused on clinical and laboratory P. mirabilis strains, where laboratory strains have determined LPS structures. Adherence and biofilm formation tests revealed significant differences between strains adhered in early stages of biofilm formation. Amounts of formed biofilm were expressed by the absorption of crystal violet. Higher biofilm amounts were formed by the strains with more negative values of zeta potential. In contrast, high cell surface hydrophobicity correlated with low biofilm amount. PMID- 27262951 TI - The role of particular tick developmental stages in the circulation of tick-borne pathogens affecting humans in Central Europe. 2. Tick-borne encephalitis virus. AB - Hard-bodied ticks transmit various pathogens, such as Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Rickettsia spp., Babesia spp., and carry numerous other microorganisms with an unknown pathogenic potential. Among them, tick-borne encephalitis virus has great importance. In Central European conditions all developmental stages of ticks participate in the zoonotic cycle of the TBE virus. According to pathogen and tick biology, the roles of larvae, nymphs and adults are different. Larvae and nymphs of Ixodes ricinus ticks are responsible for circulation in rodents and medium sized mammals; adults transfer the infection to ruminants and to next generations via transovarial transmission. All active developmental stages of I. ricinus can play role of the bridge vector, transmitting the infection to humans apart males which don't feed. The late summer peak of human infectivity is caused by the summer peak of I. ricinus nymphs' activity. The Dermacentor reticulatus tick attacks humans infrequently, but does participate in the circulation of the virus in the zoonotic foci; larvae and nymphs of the D. reticulatus ticks are responsible for circulation in rodents, mainly Microtinae, while adults transmit the infection to ruminants. PMID- 27262950 TI - Nutritional status, physical performance and disability in the elderly of the Peruvian Andes. AB - BACKGROUND: Although nutritional status plays an important part in the physical performance and disability of older people, this relationship has been little studied in developing countries. AIMS: A study on the effects of nutritional status on the physical performance and functional status of elderly people living in rural areas of the Peruvian Andes. METHODS: The study concerned 222 people aged >=65 years living in a rural area of the Peruvian Andes. The Mini Nutritional Assessment (MNA) was used to classify participants as malnourished (MNA <= 17), at risk of malnutrition (MNA 18-23), or well-nourished (MNA>= 24). The short physical performance battery (SPPB) and six-minute walking test (6MWT) were used to measure participants' physical performance. Disabilities were investigated by assessing participants' self-reported difficulty in performing one or more basic activities of daily living (ADL), and instrumental activities of daily living (IADL). RESULTS: The prevalence of malnutrition was 9.4 %, and more than half of our samples were at risk of malnutrition. After adjusting for potential confounders, malnourished individuals performed significantly worse than the other MNA groups in the SPPB (p for trend=0.001), 6MWT and IADL (p for trend < 0.0001 for both outcomes), but not in the ADL (p for trend = 0.23). Taking the well-nourished for reference, and after adjusting for potential confounders, malnutrition was significantly associated with disability in IADL (OR 5.36, 95 % CI 1.02-56.94; p = 0.05), and poor performance in the 6MWT (OR 2.73, 95 % CI 1.06-12.08; p = 0.03) and SPPB (OR 4.94, 95 % CI 1.01-24.07; p = 0.04). CONCLUSION: Poor nutritional status was found significantly associated with poor physical performance and poor functional status in elderly Peruvian individuals. PMID- 27262952 TI - Transporter protein and drug resistance of Trypanosoma. AB - Trypanosoma infection is one of the most important infections in livestock and humans. One of the main problems of its therapeutic control and treatment is the resurgence of drug resistance. One of the most studied causes of such resistance is the function of its adenosine transporter gene. A trypanosomal gene TbAT1 from Trypanosoma brucei has been cloned in yeast to demonstrate its function in the transport of adenosine and trypanocidal agents. Drug resistant trypanosomes showed a defective TbAT1 variant; furthermore, deletion of the gene and set point mutations in the transporter gene has been demonstrated from isolates from relapse patients. The molecular understanding of the mechanism of action trypanocidal agents and function of transporter gene can lead to control of drug resistance of Trypanosomes. PMID- 27262953 TI - Lessons learnt from 20 years surveillance of malaria drug resistance prior to the policy change in Burkina Faso. AB - The history of drug resistance to the previous antimalarial drugs, and the potential for resistance to evolve to Artemisinin-based combination therapies, demonstrates the necessity to set-up a good surveillance system in order to provide early warning of the development of resistance. Here we report a review summarizing the history of the surveillance of drug resistance that led to the policy change in Burkina Faso. The first Plasmodium falciparum Chloroquine Resistance strain identified in Burkina Faso was detected by an in vitro test carried out in Koudougou in 1983. Nevertheless, no further cases were reported until 1987, suggesting that resistant strains had been circulating at a low prevalence before the beginning of the systematic surveillance system from 1984. We observed a marked increase of Chloroquine-Resistance in 2002-2003 probably due to the length of follow-up as the follow-up duration was 7 or 14 days before 2002 and 28 days from 2002 onwards. Therefore, pre-2002 studies have probably under estimated the real prevalence of Chloroquine-Resistance by not detecting the late recrudescence. With a rate of 8.2% treatment failure reported in 2003, Sulfadoxine-Pyrimethamine was still efficacious for the treatment of uncomplicated malaria in Burkina Faso but this rate might rapidly increase as the result of its spreading from neighboring countries and due to its current use for both the Intermittent Preventive Treatment in pregnant women and Seasonal Malaria Chemoprophylaxis. The current strategy for the surveillance of the Artemisinin based combination treatments resistance should build on lessons learnt under the previous period of 20 years surveillance of Chloroquine and Sulfadoxine Pyrimethamine resistance (1994-2004). The most important aspect being to extend the number of sentinel sites so that data would be less patchy and could help understanding the dynamic of the resistance. PMID- 27262954 TI - Loop-mediated isothermal amplification (LAMP) assay for the rapid detection of the sexually-transmitted parasite, Trichomonas vaginalis. AB - A loop-mediated isothermal amplification (LAMP) assay was developed to detect the sexually-transmitted parasite, Trichomonas vaginalis in vaginal swabs. The presence of T. vaginalis was detected from 121 female sex workers attending a social hygiene clinic in Balibago, Angeles City, Pampanga, Philippines using culture, polymerase chain reaction (PCR), and the developed LAMP assay. The high analytical sensitivity of LAMP detected a higher prevalence of T. vaginalis (42.06%) compared to culture (8.26%) and PCR (7.44%). Additionally, this assay did not cross-react with DNAs of other trichomonads that can infect humans such as Trichomonas tenax and Pentatrichomonas hominis as well as the pathogens, Candida albicans and Staphylococcus aureus. The LAMP assay developed had a limit of detection (0.036 ng/MUl) lower than that of PCR using the primers TvK3 and TvK7 (0.36 ng/MUl). Prevalence of T. vaginalis in female sex workers in this area of the Philippines may be higher than previously estimated. Discordant results of PCR and LAMP may be due to different reactions to different kinds of inhibitors in the vaginal swabs. PMID- 27262955 TI - First detailed data on metazoan parasites of the rare species short beaked garfish Belone svetovidovi (Teleostei: Belonidae) from Tunisian coast, Central Mediterranean Sea. AB - Forty five specimens of the short beaked garfish Belone svetovidovi, a rare belonid species largely confused with the garfish Belone belone from Tunisian coast Sea were examined for metazoan parasite. Nine metazoan parasites species were identified: one monogenean (Axine sp.), 4 digeneans (Lecithostaphylus retroflexus, Tergestia acanthocephala, Aponurus laguncula and Condylocotyla pilodora metacercaria), one copepod (Bomolochus bellones), one isopod (Irona nana), one acanthocephalan (Telosentis exiguus) and one nematod Hysterotylacium sp. Most of parasite species were new records for B. svetovidovi in Tunisia. In the parasite fauna of B. svetovidovi, digenean C. pilodora metacercaria was the most prevalent species (42%) followed by Monogenea Axine sp. (36%). The total length of the host did not influence parasitic infection in B. svetovidovi. The metazoan parasite composition of B. svetovidovi revealed great similarity than those of B. belone from Tunisia supporting same ecological behavior of both hosts. PMID- 27262956 TI - The pulmonary involvement in Theileria lestoquardi naturally infected sheep. AB - Malignant Ovine Theileriosis (MOT) caused by Theileria lestoquardi is considered a major constraint for sheep production in many areas of the world including Sudan. Pulmonary oedema is thought to be the main cause of animal death, but the mechanism, the cell types involved and/or the probable cause of this pneumonia has yet to be defined. The present study was carried out to investigate the pulmonary involvement post T. lestoquardi infection and to identify the cell types involved in pneumonia. Apparently healthy sheep were exposed to ticks challenge in T. lestoquardi endemic area. Lungs impression smears and tissue sections for histopathology were processed. At necropsy, fifteen infected sheep revealed severe pneumonia associated with oedema and accumulation of creamy grayish frothy exudates. The microscopic findings of examined lungs showed emphysema, congestion, collapse and proliferation of immense amount of different kinds of cells. The current study indicates that T. lestoquardi infections are accompanied with remarkable pulmonary involvements and may lead to respiratory failure and death. PMID- 27262957 TI - Molecular identification of different Theileria and Babesia species infecting sheep in Sudan. AB - The epidemiological aspects of sheep piroplasmosis in Sudan are poorly studied, and further investigations using sensitive and precise techniques are required. In this study, the Reverse Line Blot (RLB) hybridization assay was used to detect and simultaneously differentiate between Theileria and Babesia species. DNA was extracted from blood collected on filter paper (n=219) from apparently healthy sheep from six different geographical localities in Sudan. Results indicated that Theileria ovis (88.6%), T. separata (20.1%), T. lestoquardi (16.4%) and T. annulata (16.4%) DNA could be detected in the blood samples. Single and mixed Theileria infections were detected in 74 (33.8%) and 124 (56.6%) respectively and T. ovis being the most prevalent species in the country. T. ovis and T. separata were reported for the first time in sheep in Sudan. PMID- 27262958 TI - Molecular and morphological characterization of Parabronema skrjabini of sheep and goats at three different geographical zones in Iran. AB - Parabronema skrjabini is a spirurid nematode of the family Habronematidae that lives in the abomasum of ruminants such as sheep and goats. The purpose of this study was to investigate the molecular and morphological aspects of Parabronema skrjabini in sheep and goats in Iran. The worms were collected from these animal species from three different regions. An internal transcribed spacer 2 ribosomal DNA (ITS2-rDNA) fragment of Parabronema skrjabini was amplified by polymerase chain reaction (PCR) using a pair of specific primers (Para-Ir-R and Para-Ir-F). Morphological studies based on the body length, the frontal shield, spicules of male and egg dimensions were performed. ITS2-rDNA sequences were between 167 and 299 bp in different isolates. ITS2 homology in different isolates was between 68% and 77% compared with the sequence data in GenBank. Morphological results showed that the average length of male and female worms in sheep were 16.5 mm and 36 mm and in goats 16 mm and 35.5 mm, respectively. The average length of the small and large spicules in sheep were 657.5 MUm and 304.07 MUm and in goats 653.08 MUm and 302.66 MUm, respectively. To our knowledge, this is the first study in the world exploring the genetic diversity of Parabronema in sheep and goats. Add this sentence in discussion: the low ITS2-rDNA identity in different isolates from Iran as compared to the reference sequence in GenBank (68-77%) raise questions regarding the species identity of the parasites isolated in Iran. PMID- 27262959 TI - Lungworm (Nematoda: Protostrongylidae) infection in wild and domestic ruminants from Malopolska region of Poland. AB - The conducted study has focused on domestic, as well as wild ruminant species. The post mortem examination was carried out on 68 animals, including three wild species: roe deer (Capreolus capreolus) (25 indyviduals), red deer (Cervus elaphus) (6), fallow deer (Dama dama) (5) and two domestic: sheep (Ovis aries) (14) and cattle (Bos taurus) (18). Some of the species have also been investigated in the field by the coproscopical analyses. The faecal samples from roe deer (27), fallow deer (20), red deer (36) and moose (Alces alces) (10) were collected from the environment, while from sheep (10) and goat (Capra hircus) (10)--per rectum. Based on the obtained results the following values were calculated: prevalence, mean intensity and intensity range. The post mortem examination did not reveal pulmonary nematodes neither in domestic nor in wild ungulates, however, the larvae of aforementioned parasites were often stated in the stool samples taken from the environment. All wild species, except fallow deer were infected. Consequently, six species of lungworms have been identified. The first stage larvae of Varestrongylus capreoli occurred in 11 samples of roe deer and Varestrongylus alces in one moose. The larvae of Elaphostrongylus cervi were found in 19 red deer and Varestrongylus sagittatus in 3. Furthermore, Elaphostrongylus alces larvae were noted in 6 moose. Within domestic ruminants only one sheep and two goats were infected by Muellerius capillaris. PMID- 27262960 TI - Endoparasites of exotic ungulates from the Giraffidae and Camelidae families kept ex situ. AB - Giraffes and camels are popular attractions at zoological gardens. In order to present the diversity of parasites infecting exotic ungulates from zoos, faecal samples from three giraffes and six camels from both the Silesian Zoological Garden in Chorzow, and Krakow Zoological Garden, were examined. The research was carried out over a ten-month period in 2013 and 2014. In total, 100 faecal samples from 18 animals were analysed with the use of the McMaster method. Moreover, coccidian oocysts were incubated to investigate their development and larvoscopic examination was conducted to detect the presence of nematode species. Giraffes were infected with coccidia from the genus Eimeria, and gastrointestinal nematodes from the Strongylida order, and Trichuris and Aonhotheca genera. One male giraffe was uninfected. The level of infection in giraffes was low when compared to camels kept in both of the zoos. Limited contact with other animal species contributed greatly to the lower level of infection in camels from Krakow Zoo than those from Chorzow, which were kept in the same enclosure as alpacas and Shetland ponies. PMID- 27262961 TI - Evaluation of selected oral cavity microbiota--risk factors of management complications in patients with masticatory system disorders. AB - The retrospective analysis of data on oral cavity clinical status in relation to microbiota species composition is presented. The research regards patients of different age, with and without congenital malformation, pretreatment assessed for occurrence of pathological changes in the masticatory system. Samples of the swabs collected from each patient (from dental plaque, periodontium and dental pockets) were used for identification of oral protozoans in wet slides and stained preparations; additionally, transmission electron microscope examination was performed. The material was used for in vitro cultures to identify bacteria strains. Clinically, intensity of tissue deteriorations was higher in patients with a congenital disease. Alive Trichomonas tenax and Entamoeba gingivalis, species with confirmed pathogenic impact on oral cavity and neighboring structures, were detected with higher prevalence in older patients. Enterococci, Staphylococcus aureus, various Enterobacteriaceae were more frequently detected in patients with somatic and mental retardations; in mouths of those patients, Klebsiella pneumonia and Pseudomonas aeruginosa opportunistic strains occurred. Masticatory system abnormalities favor colonization of oral cavity by exogenous species and dissemination of infections, especially dangerous for patients with congenital diseases. Oral microbiota assessment and preventive measures may be helpful to avoid subsequent peri-surgery complications. PMID- 27262962 TI - Trichinella spiralis in road-killed raccoon dogs (Nyctereutes procyonoides) in western Poland. AB - Trichinellosis is still one of the most important food-borne parasitic zoonoses and is considered as a threat to public health worldwide. The aim of this study was to use genotyping techniques to determine the prevalence of Trichinella species in wild raccoon dogs (Nyctereutes procyonoides) in western Poland. The infection rate in raccoon dogs was 0.8%. All infections were due to T. spiralis. PMID- 27262963 TI - Unusual clinical presentation of spinal echinococcal cyst imitating a malignant tumour. AB - Spinal echinococcal cyst is very uncommon and may have variable clinical presentations. We describe an exceptional case of intradural and extramedullary spinal echinococcal cyst, misguided as a spinal tumour on radiological examination and was diagnosed as echinococcal cyst on fine needle aspiration biopsy smears and subsequently on histopathological examination. PMID- 27262964 TI - Comparing adults who use cannabis medically with those who use recreationally: Results from a national sample. AB - OBJECTIVES: Cannabis has been legalized for medical use in almost half of the states in the U.S. Although laws in these states make the distinction between medical and recreational use of cannabis, the prevalence of people using medical cannabis and how distinct this group is from individuals using cannabis recreationally is unknown at a national level. METHODS: Data came from the 2013 National Survey on Drug Use and Health (NSDUH). All adults endorsing past year cannabis use who reported living in a state that had legalized medical cannabis were divided into recreational cannabis use only and medical cannabis use. Demographic and clinical characteristics were compared across these two groups. RESULTS: 17% of adults who used cannabis in the past year used cannabis medically. There were no significant differences between those who used medically versus recreationally in race, education, past year depression and prevalence of cannabis use disorders. In adjusted analyses, those with medical cannabis use were more likely to have poorer health and lower levels of alcohol use disorders and non-cannabis drug use. A third of those who reported medical cannabis use endorsed daily cannabis use compared to 11% in those who reported recreational use exclusively. CONCLUSIONS: Adults who use medical and recreational cannabis shared some characteristics, but those who used medical cannabis had higher prevalence of poor health and daily cannabis use. As more states legalize cannabis for medical use, it is important to better understand similarities and differences between people who use cannabis medically and recreationally. PMID- 27262965 TI - Reducing drinking to cope among heavy episodic drinking college women: Secondary outcomes of a web-based combined alcohol use and sexual assault risk reduction intervention. AB - College students are at high risk for engaging in heavy episodic drinking and for experiencing sexual assault. Further, drinking to cope with anxiety motives are associated with sexual assault history and drinking, and thus should be examined when targeting both sexual assault and drinking in college populations. The current study examined the effectiveness of decreasing coping with anxiety drinking motives among underage heavy episodic drinking college women (n=264). Results indicate that a web-based combined alcohol use and sexual assault risk reduction intervention was effective at decreasing drinking to cope with anxiety motives among those with stronger drinking to cope with anxiety motives at baseline. However, the alcohol-only and sexual assault-only interventions were not. Decreases in drinking motives were associated with decreases in heavy episodic drinking. This suggests that alcohol interventions in college populations may not be effectively targeting drinking motives and this preliminary study provides evidence indicating that targeting alcohol and sexual assault together may decrease drinking to cope motives among a high risk population. PMID- 27262966 TI - Fibrillatory excitation in the pulmonary vein is associated with the presence of dissociated pulmonary vein activity after isolation. AB - PURPOSE: Circumferential pulmonary vein (PV) isolation has been widely accepted for catheter ablation in patients with atrial fibrillation (AF). Dissociated PV activity might appear after PV isolation (PVI). However, little is known of dissociated PV activity. This study aimed to reveal the electrophysiological properties and clinical implications of dissociated PV activity. METHODS: The study subjects were 52 patients (62 +/- 7 years, 38 men) who underwent PVI for AF. Electrophysiological properties of the left atrium (LA) and PVs during and after PVI were investigated. RESULTS: Out of 181 targeted PVs, 177 with successful isolation were analyzed. Dissociated PV activity appeared in 14 PVs (8 %) in 12 patients (23 %) after PVI; from the left superior PV in eight, right superior PV in five, and left inferior PV in one. The mean cycle length of dissociated PV activity was 4277 +/- 2565 ms. The presence of AF prior to achieving PVI was significantly higher in PV without dissociated PV activity (105 out of 163, 64 %) than in PV with dissociated PV activity (five out of 14, 36 %, P = 0.03). The observed dissociated PV activity was enhanced (new appearance or reduced cycle length) by isoproterenol and suppressed by pacing within the isolated PV. CONCLUSION: Dissociated PV activity, although influenced by uncertain factors such as overdrive suppression and autonomic situations, would be an indicator of LA-PV bidirectional block and might not be the target of additional ablation after PVI. PMID- 27262968 TI - Rural-urban differences in the prevalence of cognitive impairment in independent community-dwelling elderly residents of Ojiya city, Niigata Prefecture, Japan. AB - BACKGROUND: This study aimed to examine rural-urban differences in the prevalence of cognitive impairment in Japan. METHODS: We targeted 592 residents aged 65 years and older who did not use long-term care insurance services in one rural and two urban areas in Ojiya City, Japan. Of these, 537 (90.7 %) participated in the study. The revised Hasegawa's dementia scale (HDS-R) was used to assess cognitive function, and cognitive impairment was defined as a HDS-R score <=20. Lifestyle information was obtained through interviews. The prevalence of cognitive impairment was compared according to the levels of predictor variables by odds ratios (ORs) calculated by a logistic regression analysis. RESULTS: Mean age of participants was 75.7 years (SD 7.0). The prevalence of cognitive impairment was 20/239 (8.4 %) in the rural area and 6/298 (2.0 %) in the urban areas, for a total of 26/537 (4.8 %) overall. Men tended to have a higher prevalence of cognitive impairment (P = 0.0628), and age was associated with cognitive impairment (P for trend <0.0001). The rural area had a significantly higher prevalence of cognitive impairment (age- and sex-adjusted OR = 4.04, 95 % CI: 1.54-10.62) than urban areas. This difference was significant after adjusting for other lifestyle factors. CONCLUSIONS: The prevalence of cognitive impairment was higher in the rural area relative to urban areas in Ojiya city. This regional difference suggests the existence of potentially modifiable factors other than lifestyle in relation to cognitive impairment. PMID- 27262967 TI - Behavioral profile assessment in offspring of Swiss mice treated during pregnancy and lactation with caffeine. AB - The association between caffeine consumption and various psychiatric manifestations has long been observed. The objective was to assess the behavioral profile in offspring of Swiss mice treated during pregnancy and lactation with caffeine. For this purpose, two groups (n = 6 each and BW ~ 35 g) of female mice were treated during pregnancy and lactation by: tap water and caffeine solution at a concentration of 0.3 mg/mL through oral route. The offspring obtained, by completing 70 days of life, was underwent a behavioral battery test. Statistical analysis was performed by student t test and the different significance adopted was p < 0.05. According to our results, it was not found any significant differences in tail suspension and forced swimming tests. In anxiety related responses however, the mice of caffeine group had greater number of fecal pellets (178 %, p = 0.001) in the open field test, higher number of attempts (51 %, p = 0.03) in light-dark box and decreased percentage of entries in open arms (41 %, p = 0.01) in elevated plus maze test. Moreover, in the marble burying test, there was a significant decrease in the number of buried marbles compared with controls (110 %, p = 0,002). In the meantime, in the von Frey test, it was observed an exacerbation of mechanical allodynia both in basal conditions and after the carrageenan administration (p < 0.001). Furthermore, caffeine treatment during pregnancy and lactation causes long-term behavioral changes in the mice offspring that manifest later in life. PMID- 27262969 TI - The use of the marine gastropod, Cellana tramoserica, as a biomonitor of metal contamination in near shore environments. AB - The use of the marine gastropod, Cellana tramoserica, as a biomonitor of metal exposure was investigated. The factors influencing metal concentrations, such as mass, gender, substrate, shoreline position and temporal variation were examined. Tissue metal concentrations were mostly found to be independent of mass and gender. When metal concentrations were significantly correlated with mass, correlations were low and explained little variability. The underlying substrate and position in the littoral zone had only a small influence on metal concentrations. Variation between individuals, inherent variability due to genetic variability, was the most significant contribution to the overall variation in metal concentrations, resulting in positive skewing of population distributions. The mean metal concentrations varied temporally; metal masses were relatively constant with fluctuations in metal concentrations related to fluctuations in metal body burdens. The populations from a metal-contaminated site had significantly higher tissue Cu, Zn, As and Pb concentrations than the populations from relatively uncontaminated locations. C. tramoserica therefore can be considered to be a net accumulator of metals. A sample number of >10 is required to detect changes of 25 % from the mean concentrations at uncontaminated locations. This species meets the requirements of a suitable biomonitor for metal contaminants in the environment i.e. hardy, sessile, widespread, sufficient tissue mass and a metal accumulator. As the measurement of metal concentrations in C. tramesoria were influenced by substrate and shore position and, sometimes, mass, sites with similar substrates and organisms of similar mass and shoreline position should be chosen for comparison. When comparing metal concentrations in gastropods from different locations, they should be collected over the same period to minimise variability due to mass differences, spawning and other seasonal/temporal effects. PMID- 27262970 TI - Bioefficacy and persistence of acephate in mungbean Vigna radiata (L.) Wilczek. AB - The bioefficacy, persistence and metabolism of foliar application of acephate 75 SP at the respective recommended and double doses of 1500 and 3000 g a.i. ha(-1) were studied on kharif mungbean crop. Acephate gave a very effective control of the pod borer, Helicoverpa armigera (Hubner) at the tested doses on mungbean crop throughout the cropping season, besides recording lower percent pod damage and higher grain yield. The recommended dose of acephate also recorded higher net returns and thus indicating its superiority. Persistence of acephate in mungbean leaves and soil was studied following applications of acephate @ 1500 and 3000 g a.i. ha(-1) at 30 days after sowing. Residues of acephate in mungbean leaves and soil were estimated using gas liquid chromatograph (GLC) and confirmed on gas chromatograph-mass spectrometry (GC-MS). Half-life periods for acephate in mungbean leaves were observed to be 2.98 and 3.27 days at single and double the application rates, respectively. Residues of acephate dissipated below its limit of quantification (LOQ) of 0.05 mg kg(-1) after 20 and 25 days at single and double the application dosage, respectively. Similarly, half-life periods for acephate in mungbean soil were observed to be 1.86 and 1.94 days at single and double the application rates, respectively. Residues of acephate dissipated below its LOQ of 0.05 mg kg(-1) after 10 and 15 days at single and double the application dosage, respectively. PMID- 27262971 TI - A prediction model of vaginal birth after cesarean in the preterm period. AB - BACKGROUND: A validated model exists that predicts the probability of vaginal birth after cesarean delivery in patients at term who are undergoing a trial of labor after cesarean delivery. However, a model that predicts the success of a vaginal birth after cesarean delivery in the preterm period has not been developed. OBJECTIVE: We sought to develop and validate a predictive model for vaginal birth after cesarean delivery for women undergoing a trial of labor after cesarean delivery during the preterm period. STUDY DESIGN: We performed a secondary analysis of a prospective cohort study designed to evaluate perinatal outcomes in women with a prior cesarean scar. We included women with 1 prior low transverse cesarean delivery undergoing a trial of labor after cesarean delivery with a vertex singleton pregnancy in the preterm period (26-36 weeks). Using multivariable logistic regression modeling, we constructed a predictive model for vaginal birth after cesarean delivery with information known at admission for preterm delivery. Using a 70% to 30% random split of the data, the model was developed in the training data and subsequently confirmed in the validation data. Predictions and area under the curve were based on a 10-fold cross-validated jackknife estimation and based on 1000 bootstrap resampling methods. The adequacy of all models was evaluated based on the Hosmer-Lemeshow goodness-of-fit test. RESULTS: One thousand two hundred ninety-five women met our criteria for analysis. The significant predictors of vaginal birth after cesarean delivery success were chronic hypertension, hypertensive disease of pregnancy (gestational hypertension or preeclampsia), prior vaginal delivery, dilation on cervical examination at admission, prior vaginal birth after cesarean delivery, a recurring indication in a prior cesarean delivery, and induction of labor as well as a 2-way interactions between dilation and hypertensive disease of pregnancy, dilation and diabetes mellitus (pregestational or gestational), and induction of labor and hypertensive disease of pregnancy. The area under the curve from the prediction model was 0.80 (95% confidence interval, 0.77-0.83) and the model fit the data well (Hosmer-Lemeshow P = .367). The bootstrap and 10-fold cross validated jackknife estimates of the corrected area under the curve of the model were 0.78 (95% confidence interval, 0.74-0.82) and 0.77 (95% confidence interval, 0.73-0.82), respectively, following incorporation of regression shrinkage. CONCLUSION: A cross-validated predictive model was created for patients undergoing a trial of labor after cesarean delivery in the preterm period using 8 variables known on admission. These factors were notably different from factors used in the model for term patients. This new model can be used to counsel patients in the preterm period who want to undergo a trial of labor after cesarean delivery on their predicted vaginal birth after cesarean delivery success. PMID- 27262972 TI - Detoxification from opiates during pregnancy: stressing the fetal brain. PMID- 27262973 TI - Reply. PMID- 27262974 TI - Randomized controlled trial of prolonged second stage: extending the time limit vs usual guidelines. PMID- 27262975 TI - Reply. PMID- 27262976 TI - Infrainguinal Vein Graft Stenoses: Long-Term Outcomes of Graft Angioplasty. AB - OBJECTIVE: Graft angioplasty combines the durability and ability of surgical bypasses to treat long arterial occlusions with the minimally invasive nature of endovascular procedures. The purpose of this study was to evaluate the efficacy of single and repeated graft angioplasty in revising failing infrainguinal vein bypass grafts and to determine predictors of medium- and long-term freedom from revision after graft angioplasty. METHOD: This was a retrospective analysis from a prospectively maintained database. Consecutive endovascular revisions of graft threatening lesions identified by duplex ultrasound surveillance were reviewed from 2003 to 2010. Patients were followed up until death, major amputation, or the end of follow-up, with the data last updated on January 1, 2013. RESULTS: 178 graft angioplasty procedures performed in 114 bypass grafts in 103 limbs from 98 patients were studied. At 5 years, freedom from revision was 22.6%, graft survival was 45.8%, amputation-free survival was 57.9%, and patient survival was 64.9%. Analysis of repeated angioplasties found no evidence that effectiveness diminishes significantly with the number of previous angioplasties performed (p=.892). Higher Rutherford Grade of ischemia and longer time interval from index surgery to first angioplasty were significant positive predictors of medium- and long-term patency. CONCLUSION: Percutaneous transluminal angioplasty of infrainguinal vein grafts is safe and effective in the treatment of failing grafts identified by duplex surveillance. Graft angioplasties do not lose effectiveness when repeated and have shown cumulative benefit in prolonging graft survival. Treatment of claudicants and time interval from graft implantation of more than 6 months at the time of first angioplasty are positive predictors of at least medium-term patency after graft angioplasty. PMID- 27262978 TI - Superficial warming and cooling of the leg affects walking speed and neuromuscular impairments in people with spastic paraparesis. AB - BACKGROUND: People with hereditary and spontaneous spastic paraparesis (HSSP) report that their legs are stiffer and walking is slower when their legs are cold. OBJECTIVES: This study explored the effects of prolonged superficial cooling and warming of the lower leg on walking speed and local measures of neuromuscular impairments. METHODS: This was a randomised pre- and post intervention study of 22 HSSP participants and 19 matched healthy controls. On 2 separate occasions, one lower leg was cooled or warmed. Measurements included walking speed and measures of lower limb impairment: ankle movement, passive muscle stiffness, spasticity (stretch reflex size), amplitude and rate of force generation in dorsi- and plantarflexors and central and peripheral nerve conduction time/velocity. RESULTS: For both participants and controls, cooling decreased walking speed, especially for HSSP participants. For both groups, cooling decreased the dorsiflexor rate and amplitude of force generation and peripheral nerve conduction velocity and increased spasticity. Warming increased dorsiflexor rate of force generation and nerve conduction velocity and decreased spasticity. CONCLUSIONS: Superficial cooling significantly reduced walking speed for people with HSSP. Temperature changes were associated with changes in neuromuscular impairments for both people with spastic paraparesis and controls. This study does not support the use of localised cooling in rehabilitation for people with spastic paraparesis as reported in other neurological conditions. Rehabilitation interventions that help prevent heat loss (insulation) or improve limb temperature via passive or active means, particularly when the legs and/or environment are cool, may benefit people with spastic paraparesis. PMID- 27262977 TI - Commentary on 'Predictors for Recanalization of the Great Saphenous Vein in RCTs 1 Year After Endovenous Thermal Ablation': The Dark Side of Systematic Reviews. PMID- 27262979 TI - Factors associated with not meeting the recommendations for micronutrient intake in critically ill children. AB - OBJECTIVE: Children admitted to the intensive care unit (ICU) are at risk of not meeting their nutritional requirements. This study aimed to identify factors associated with failure to meet the dietary recommended intake (DRI) of zinc, selenium, cholecalciferol, and thiamine in critically ill children receiving enteral tube feeding during their stay in the ICU. METHODS: We analyzed prospectively 260 cases, corresponding to 206 patients who received enteral tube feeding for a minimum of 3 days up to 10 days during the first 10 d of ICU stay. Individual intake was compared to estimated average requirement (EAR) and adequate intake (AI) values during the first 10 d of ICU stay. The outcome variable was defined as not meeting the recommended intake of the micronutrients studied. Potential explanatory variables for the outcome were age <1 year, malnutrition (WHO), clinical severity scores, heart disease, severe sepsis or septic shock, use of alpha-adrenergic drugs, and renal replacement therapy (RRT). The effect of the explanatory variables on the outcome was analyzed by logistic regression analysis. RESULTS: The majority of patients did not meet the recommendations for micronutrients. After adjusting for covariates, age <1 year, malnutrition, heart disease, use of alpha-adrenergic drugs, and renal replacement therapy were associated with failure to meet the recommendations for at least one of the micronutrients studied. CONCLUSIONS: Factors associated with failure to meet the recommendations for micronutrient intake in children receiving enteral tube feeding during their ICU stay are linked to patients' low weight, restriction in fluid intake, and clinical severity of the disease. PMID- 27262980 TI - Japanese macaque (Macaca fuscata) mothers huddle with their young offspring instead of adult females for thermoregulation. AB - It is unclear whom animals select to huddle with for thermoregulation. In this study, we investigated whom Japanese macaque (Macaca fuscata) mothers huddled with-their young offspring or other adult group members-when there is need for thermoregulation. We used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama Prefecture, Japan. A majority of huddling among adult females was recorded during winter season (December, January, and February). Females who had young (0- or 1-year-old) offspring huddled less frequently with other adult females compared to females who did not have young offspring in winter. However, including young offspring, the frequency of huddling with any other individuals did not differ by whether females had young offspring. Moreover, the females who did not have young offspring huddled with other adult females more often in cloudy than in sunny weather during winter season. In contrast, females who had young offspring increased huddling with their young offspring in cloudy than in sunny weather, but did not do so with other adult females. This study indicates that Japanese macaque mothers huddle with their young offspring instead of other adult females when there is need for thermoregulation. PMID- 27262981 TI - Epidermal growth factor-induced hydrogen peroxide production is mediated by dual oxidase 1. AB - Stimulation of mammalian cells by epidermal growth factor (EGF) elicits complex signaling events, including an increase in hydrogen peroxide (H2O2) production. Understanding the significance of this response is limited by the fact that the source of EGF-induced H2O2 production is unknown. Here we show that EGF-induced H2O2 production in epidermal cell lines is dependent on the agonist-induced calcium signal. We analyzed the expression of NADPH oxidase isoforms and found both A431 and HaCaT cells to express the calcium-sensitive NADPH oxidase, Dual oxidase 1 (Duox1) and its protein partner Duox activator 1 (DuoxA1). Inhibition of Duox1 expression by small interfering RNAs eliminated EGF-induced H2O2 production in both cell lines. We also demonstrate that H2O2 production by Duox1 leads to the oxidation of thioredoxin-1 and the cytosolic peroxiredoxins. Our observations provide evidence for a new signaling paradigm in which changes of intracellular calcium concentration are transformed into redox signals through the calcium-dependent activation of Duox1. PMID- 27262982 TI - Future hydrological regimes and glacier cover in the Everest region: The case study of the upper Dudh Koshi basin. AB - Assessment of future water resources under climate change is required in the Himalayas, where hydrological cycle is poorly studied and little understood. This study focuses on the upper Dudh Koshi river of Nepal (151km(2), 4200-8848ma.s.l.) at the toe of Mt. Everest, nesting the debris covered Khumbu, and Khangri Nup glaciers (62km(2)). New data gathered during three years of field campaigns (2012 2014) were used to set up a glacio-hydrological model describing stream flows, snow and ice melt, ice cover thickness and glaciers' flow dynamics. The model was validated, and used to assess changes of the hydrological cycle until 2100. Climate projections are used from three Global Climate Models used in the recent IPCC AR5 under RCP2.6, RCP4.5 and RCP8.5. Flow statistics are estimated for two reference decades 2045-2054, and 2090-2099, and compared against control run CR, 2012-2014. During CR we found a contribution of ice melt to stream flows of 55% yearly, with snow melt contributing for 19%. Future flows are predicted to increase in monsoon season, but to decrease yearly (-4% vs CR on average) at 2045 2054. At the end of century large reduction would occur in all seasons, i.e. -26% vs CR on average at 2090-2099. At half century yearly contribution of ice melt would be on average 45%, and snow melt 28%. At the end of century ice melt would be 31%, and snow contribution 39%. Glaciers in the area are projected to thin largely up to 6500ma.s.l. until 2100, reducing their volume by -50% or more, and their ice covered area by -30% or more. According to our results, in the future water resources in the upper Dudh Koshi would decrease, and depend largely upon snow melt and rainfall, so that adaptation measures to modified water availability will be required. PMID- 27262983 TI - Sorption, photodegradation, and chemical transformation of naproxen and ibuprofen in soils and water. AB - Pharmaceutically active compounds (PhACs) are released into the environment where they undergo soil sorption, photodegradation, and chemical transformation into structurally similar compounds. Here we report on studies of naproxen (NAP) and ibuprofen (IBP), two widely-used nonsteroidal anti-inflammatory drugs (NSAIDS), in soils and water. Organic matter (OM) was observed to play an important role in each of these processes. Sorption was observed to be stronger and nonlinear in higher OM soils while weaker but still significant in lower OM, higher clay soils; the amphiphilic nature of these two PhACs combined with the complex charged and nonpolar surfaces available in the soil was observed to control the sorption behavior. Simulated solar photodegradation rates of NAP and IBP in water were observed to change in the presence of humic acid or fulvic acid. Structural analogs of each compound were observed as the result of chemical transformation in both photoexposed aqueous solutions and non-photoexposed soil. Two of these transformation products were detected as both soil and photo transformation products for both PhACs. OM was observed to influence the chemical transformation of both pharmaceuticals. PMID- 27262984 TI - Fluid mechanical dispersion of airborne pollutants inside urban street canyons subjecting to multi-component ventilation and unstable thermal stratifications. AB - The pedestrian level pollutant transport in street canyons with multiple aspect ratios (H/W) is numerically investigated in the present work, regarding of various unstable thermal stratification scenarios and plain surrounding. Non isothermal turbulent wind flow, temperature field and pollutant spread within and above the street canyons are solved by the realizable k-epsilon turbulence model along with the enhanced wall treatment. One-vortex flow regime is observed for shallow canyons with H/W=0.5, whereas multi-vortex flow regime is observed for deep canyons with H/W=2.0. Both one-vortex and multi-vortex regimes could be observed for the street canyons with H/W=1.0, where the secondary vortex could be initiated by the flow separation and intensified by unstable thermal stratification. Air exchange rate (AER) and pollutant retention time are adopted to respectively evaluate the street canyon ventilation and pollutant removal performance. A second-order polynomial functional relationship is established between AER and Richardson number (Ri). Similar functional relationship could be established between retention time and Ri, and it is only valid for canyons with one-vortex flow regime. In addition, retention time could be prolonged abruptly for canyons with multi-vortex flow regime. Very weak secondary vortex is presented at the ground level of deep canyons with mild stratification, where pollutants are highly accumulated. However, with the decrease of Ri, pollutant concentration adjacent to the ground reduces accordingly. Present research could be applied to guide the urban design and city planning for enhancing pedestrian environment. PMID- 27262985 TI - Oxidative stress mediates dibutyl phthalateinduced anxiety-like behavior in Kunming mice. AB - Among all phthalate esters, dibutyl phthalate (DBP) is only second to di-(2 ethylhexyl) phthalate (DEHP) in terms of adverse health outcomes, and its potential cerebral neurotoxicity has raised concern in recent years. DBP exposure has been reported to be responsible for neurobehavioral effects and related neurological diseases. In this study, we found that neurobehavioral changes induced by DBP may be mediated by oxidative damage in the mouse brain, and that the co-administration of Mangiferin (MAG, 50mg/kg/day) may protect the brain against oxidative damage caused by DBP exposure. The results of ethological analysis (elevated plus maze test and open-field test), histopathological examination of the brain, and assessments of oxidative stress (OS) in the mouse brain showed that there is a link between oxidative stress and anxiety-like behavior produced by DBP at higher doses (25 or 125mg/kg/day). Biomarkers of oxidative stress encompass reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA) and DPC coefficients (DPC). MAG (50mg/kg/day),administered as an antioxidant,can attenuatetheanxiety-like behavior of the tested mice. PMID- 27262986 TI - Impact of high-fat diet on liver genes expression profiles in mice model of nonalcoholic fatty liver disease. AB - Evidences have shown that NAFLD influences expression of some drug metabolic enzyme genes. This study aims to investigate the role of HFD-induced NAFLD in regulating the transcription of genes, particularly the drug metabolizing genes variation. Transcriptome analysis demonstrated that HFD feeding caused the 150 genes expression to change, most genes associated with lipid metabolism, inflammatory, oxidative stress and oxidoreductase activity up-regulated, whereas most genes involved in nucleic acid metabolism repressed. The genes involved in drug metabolism had 16 down-regulated and 21 up-regulated in NAFLD. The over-4 fold change genes included the down-regulation of Cyp8b1, Cyp7a1, Sult3a1, Sult1e1, Cyp17a1, Cyp3a41a, Gstt3, Cyp51, Cyp2c54 and Cyp4f14, and the up regulation of Asns, Past1, Cyp2c55, Gstm2, Cyp2e1 and Gstaalpha1. In conclusion, significant alterations in the expression of drug metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions or drug toxicity in nonalcoholic fatty liver disease. PMID- 27262987 TI - Lead selenide nanoparticles-induced oxidative damage of kidney in rats. AB - OBJECTIVE: To investigate the effect of lead selenide nanoparticles (nano PbSe) on kidney in rats. METHOD: Specific pathogen free SD rats were randomly divided into 4 groups (8 rats/group), and injected with of 0mg/kg (control group), 10mg/kg (low dose group), 20mg/kg (middle dose group), or 30mg/kg (high dose group) nano PbSe respectively. Seven weeks after injection, the serum was taken from rats for the detection of blood urea nitrogen (BUN), creatinine (Cr) and uric acid (UA). Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) levels were detected using renal tissue homogenate. Pathological examination was performed on kidney sections. RESULTS: The levels of BUN and Cr in three exposure groups were significantly increased compared with those of control group. Levels of UA in middle dose and high dose group were higher than those in the control group. Levels of SOD, GSH-Px and T-AOC in three exposure groups were markedly decreased compared with those in the control group. Levels of MDA in three exposure groups were higher than those in the control group. Pathological changes at different levels of kidneys were observed, and the damage was more serious with the increase of concentration. CONCLUSIONS: Nano PbSe can lead to oxidative damage to the kidney, with the toxicity positively correlates to the dosage. PMID- 27262988 TI - Evaluation of urinary metal concentrations and sperm DNA damage in infertile men from an infertility clinic. AB - This study aimed to examine associations between urinary metal concentrations and sperm DNA damage. Thirteen metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] were detected in urine samples of 207 infertile men from an infertility clinic using inductively coupled plasma mass spectrometry, and also, sperm DNA damage (tail length, percent DNA tail, and tail distributed moment) were assessed using neutral comet assay. We found that urinary Hg and Ni were associated with increasing trends for tail length (both p for trend<0.05), and that urinary Mn was associated with increasing trend for tail distributed moment (p for trend=0.02). These associations did persist even when considering multiple metals. Our results suggest that environmental exposure to Hg, Mn, and Ni may be associated with increased sperm DNA damage. PMID- 27262989 TI - Organochlorine pesticides and PCBs (including dl-PCBs) in human milk samples collected from multiparae from Croatia and comparison with primiparae. AB - This study investigated the levels of 20 congeners of polychlorinated biphenyls (PCBs), including toxic dioxin-like PCBs and 7 organochlorine pesticides (OCPs) in 33 human milk samples collected in 2011 from multiparae living in Zadar, Croatia. Concentrations of ?PCBs, ?DDTs, ?HCHs and HCB in samples ranged from 11.7 to 146.3, 8.7 to 89.2, 0.9 to 28.4, and 150.1 for vortioxetine, m/z 407.2->100.3 for carvedilol, m/z 423.2->100.1 for 4-hydroxyphenyl carvedilol and m/z 285.2 >193.1 for diazepam (IS) using a positive electrospray ionization interface. The method was validated over a concentration range of 0.5-100ng/mL for vortioxetine, 0.5-1000ng/mL for carvedilol and 0.1-50ng/mL for 4-hydroxyphenyl carvedilol. Total time for each chromatograph was 3.0min. The intra- and inter-day precision and accuracy of the quality control samples at low, medium, and high concentration levels exhibited relative standard deviations (RSD)<11.6% and the accuracy values ranged from -12.2% to 11.3%. The analytical method was successfully applied to a pharmacokinetic interaction study of vortioxetine and carvedilol after oral administration vortioxetine and carvedilol in rats. Results suggested that the co-administration of vortioxetine and carvedilol results in a significant drug interaction in rats. PMID- 27262995 TI - Microvascular Outcomes in Patients with Type 2 Diabetes Treated with Vildagliptin vs. Sulfonylurea: A Retrospective Study Using German Electronic Medical Records. AB - INTRODUCTION: Preliminary data suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors may reduce microvascular events, but there is a little evidence to support this from adequate real-world studies. This study aimed to compare microvascular outcomes between patients-prescribed vildagliptin and those prescribed sulfonylurea (SU). METHODS: This retrospective cohort study was conducted on a large sample from the German electronic medical records database IMS Lifelink Disease Analyzer. We used propensity score-matched samples of patients prescribed either vildagliptin or SU. Exposure was defined as therapy (SU or vildagliptin); primary outcomes were a diagnosis of retinopathy, nephropathy, neuropathy, or diabetic foot ulcer over the observation period in patients with no previous record of these outcomes. Secondary outcome was a composite of any primary outcome occurring in the observation period. RESULTS: In total, 16,321 patients prescribed SU and 4481 prescribed vildagliptin met the inclusion criteria. After propensity score matching, each sample comprised 3015 patients. Mean age was 63.7/64.6 years for SU/vildagliptin, respectively, with mean disease duration of 3.2/3.1 years, and mean treatment duration of 2.5/2.3 years. Treatment with vildagliptin was associated with a significant lower incidence of retinopathy [odds ratio (OR) = 0.55, P = 0.0004], neuropathy (OR 0.71, P = 0.0001), and composite outcome (OR 0.70, P < 0.0001). Incidences of nephropathy and diabetic foot ulcer were lower for vildagliptin, but not significantly so (OR 0.90, P = 0.3920; OR 0.76, P = 0.0742, respectively). There were no significant differences in incident rate ratios (all P > 0.05). CONCLUSION: Treatment with vildagliptin was associated with a reduced incidence of microvascular complications, especially neuropathy and retinopathy, compared to treatment with SU in this clinical practice setting. FUNDING: Novartis Pharma AG. PMID- 27262996 TI - Pivotal role of high-mobility group box 1 (HMGB1) signaling pathways in glioma development and progression. AB - Human gliomas represent the most common type of intracranial tumors, with highest morbidity and mortality. They are characterized by excessive invasiveness and cell proliferation while their unclear boundaries predispose to tumor recurrence soon after conventional treatment. Elucidation of the molecular mechanisms implicated in their development and/or treatment resistance is highly demanded. The high-mobility group box 1 (HMGB1) protein, a highly conserved nuclear protein that functions as a chromatin-binding factor, facilitating nucleosome stabilization and regulating gene transcription, has been implicated in glioma formation and progression. Extracellular released HMGB1 binds to high-affinity receptors, including the receptor for advanced glycation end-products (RAGE) and toll-like receptor (TLR)-2, TLR-4, and TLR-9. Upon receptor binding, HMGB1 triggers the activation of key signaling pathways and immune responses, involved in the regulation of cell growth, differentiation, motility, and apoptosis. Based on the type of receptor and/or cell, HMGB1 is capable to promote oncogenesis or suppress tumor growth, thus affecting treatment efficacy. Herein, we discuss recent evidence implicating HMGB1 in glioma cell differentiation, proliferation, and metastasis with both clinical and prognostic significance. In addition, potential therapeutic approaches to target this protein in order to reduce chemoresistance of glioma cells are also addressed. PMID- 27262997 TI - Obesity-Induced Hypertension: Brain Signaling Pathways. AB - Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review highlights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension. PMID- 27262999 TI - Microbial production of propanol. AB - Both, n-propanol and isopropanol are industrially attractive value-added molecules that can be produced by microbes from renewable resources. The development of cost-effective fermentation processes may allow using these alcohols as a biofuel component, or as a precursor for the chemical synthesis of propylene. This review reports and discusses the recent progress which has been made in the biochemical production of propanol. Several synthetic propanol producing pathways were developed that vary with respect to stoichiometry and metabolic entry point. These pathways were expressed in different host organisms and enabled propanol production from various renewable feedstocks. Furthermore, it was shown that the optimization of fermentation conditions greatly improved process performance, in particular, when continuous product removal prevented accumulation of toxic propanol levels. Although these advanced metabolic engineering and fermentation strategies have facilitated significant progress in the biochemical production of propanol, the currently achieved propanol yields and productivities appear to be insufficient to compete with chemical propanol synthesis. The development of biosynthetic pathways with improved propanol yields, the breeding or identification of microorganisms with higher propanol tolerance, and the engineering of propanol producer strains that efficiently utilize low-cost feedstocks are the major challenges on the way to industrially relevant microbial propanol production processes. PMID- 27262998 TI - Evolution and Distribution of Teleost myomiRNAs: Functionally Diversified myomiRs in Teleosts. AB - Myosin heavy chain (MYH) genes belong to a multigene family, and the regulated expression of each member determines the physiological and contractile muscle properties. Among these, MYH6, MYH7, and MYH14 occupy unique positions in the mammalian MYH gene family because of their specific expression in slow/cardiac muscles and the existence of intronic micro(mi) RNAs. MYH6, MYH7, and MYH14 encode miR-208a, miR-208b, and miR-499, respectively. These MYH encoded miRNAs are designated as myomiRs because of their muscle-specific expression and functions. In mammals, myomiRs and host MYHs form a transcription network involved in muscle fiber-type specification; thus, genomic positions and expression patterns of them are well conserved. However, our previous studies revealed divergent distribution and expression of MYH14/miR-499 among teleosts, suggesting the unique evolution of myomiRs and host MYHs in teleosts. Here, we examined distribution and expression of myomiRs and host MYHs in various teleost species. The major cardiac MYH isoforms in teleosts are an intronless gene, atrial myosin heavy chain (amhc), and ventricular myosin heavy chain (vmhc) gene that encodes an intronic miRNA, miR-736. Phylogenetic analysis revealed that vmhc/miR-736 is a teleost-specific myomiR that differed from tetrapoda MYH6/MYH7/miR-208s. Teleost genomes also contain species-specific orthologs in addition to vmhc and amhc, indicating complex gene duplication and gene loss events during teleost evolution. In medaka and torafugu, miR-499 was highly expressed in slow/cardiac muscles whereas the expression of miR-736 was quite low and not muscle specific. These results suggest functional diversification of myomiRs in teleost with the diversification of host MYHs. PMID- 27263000 TI - Plant biomass degrading ability of the coprophilic ascomycete fungus Podospora anserina. AB - The degradation of plant biomass is a major challenge towards the production of bio-based compounds and materials. As key lignocellulolytic enzyme producers, filamentous fungi represent a promising reservoir to tackle this challenge. Among them, the coprophilous ascomycete Podospora anserina has been used as a model organism to study various biological mechanisms because its genetics are well understood and controlled. In 2008, the sequencing of its genome revealed a great diversity of enzymes targeting plant carbohydrates and lignin. Since then, a large array of lignocellulose-acting enzymes has been characterized and genetic analyses have enabled the understanding of P. anserina metabolism and development on plant biomass. Overall, these research efforts shed light on P. anserina strategy to unlock recalcitrant lignocellulose deconstruction. PMID- 27263001 TI - Agrobacterium tumefaciens-mediated transformation of Botryosphaeria dothidea. AB - Botryosphaeria dothidea is a severe causal agent of die-back and cankers of many woody plants and causes great losses in many regions. The pathogenic mechanism of this pathogen has not been well explored due to lack of mutants and genetic information. In this study, we developed an Agrobacterium tumefaciens-mediated transformation (ATMT) protocol for B. dothidea protoplasts using vector pBHt2 containing the hph gene as a selection marker under the control of trp C promoter. Using this protocol we successfully generated the B. dothidea transformants with efficiency about 23 transformants per 10(5) protoplasts. This is the first report of genetic transformation of B. dothidea via ATMT and this protocol provides an effective tool for B. dothidea genome manipulation, gene identification and functional analysis. PMID- 27263002 TI - Renewable microbial lipid production from Oleaginous Yeast: some surfactants greatly improved lipid production of Rhodosporidium toruloides. AB - Microbial oil is drawing increasing interest worldwide as an alternative non-food oil feedstock for biodiesel industry. Nowadays researchers have been increasingly focused on the improvement of microbial oil production process. Oleaginous yeast Rhodosporidium toruloides (R. toruloides) is considered an important candidate due to its excellent capabilities of lipid accumulation, broad adaptabilities to various carbon substrates, and the potential of co-production of some pigments. In present work, the individual effects of non-ionic, cationic, and anionic surfactant on cell growth and lipid accumulation of R. toruloides were investigated for the first time. Interesting results were noticed when some anionic surfactants were supplemented. The most significant effect was observed with addition of 0.2 % (w/v) sodium lignosulfonate, that biomass concentration, lipid concentration, and lipid yield was increased by 25.1, 44.9, and 15.7 %, respectively. The fatty acid compositions of R. toruloides lipids remained unchanged, which is similar to that of vegetable oils, and is considered potential feedstock for biodiesel preparation. PMID- 27263003 TI - Loop mediated isothermal amplification (LAMP) assay for detection of coconut root wilt disease and arecanut yellow leaf disease phytoplasma. AB - The coconut root wilt disease (RWD) and the arecanut yellow leaf disease (YLD) are two major phytoplasma associated diseases affecting palms in South India. Greatly debilitating the palm health, these diseases cause substantial yield reduction and economic loss to farmers. A rapid and robust diagnostic technique is crucial in efficient disease management. We established phytoplasma 16S rDNA targeted loop mediated isothermal amplification (LAMP) and real time LAMP based diagnostics for coconut RWD and arecanut YLD. The LAMP reaction was set at 65 degrees C and end point detection made using hydroxynaphthol blue (HNB) and agarose gel electrophoresis. Molecular typing of LAMP products were made with restriction enzyme HpyCH4 V. Conventional PCR with LAMP external primers and sequencing of amplicons was carried out. Real time LAMP was performed on the Genei II platform (Optigene Ltd., UK). An annealing curve analysis was programmed at the end of the incubation to check the fidelity of the amplicons. The phytoplasma positive samples produced typical ladder like bands on agarose gel, showed colour change from violet to blue with HNB and produced unique annealing peak at 85 +/- 0.5 degrees C in the real time detection. Restriction digestion produced predicted size fragments. Sequencing and BLASTN analysis confirmed that the amplification corresponded to phytoplasma 16S rRNA gene. LAMP method devised here was found to be more robust compared to conventional nested PCR and hence has potential applications in detection of phytoplasma from symptomatic palm samples and in rapid screening of healthy seedlings. PMID- 27263004 TI - Isolation and characterization of Magnetospirillum from saline lagoon. AB - Magnetotactic bacteria (MTB) are aquatic prokaryotes that orient themselves to earth's magnetic field with the help of intracellular organelle magnetosomes. Although many species of MTB have been identified, the isolation of MTB is a challenging task due to the lack of systematic isolation procedure and/or commercial media. In this study, we are reporting the isolation of magnetotactic spirillum from the Pulicat lagoon, India using a systematic and selective procedure. Sampling site was chosen on the basis of physicochemical properties of the ecosystem and the catalysed reporter deposition fluorescence in situ hybridization (CARD-FISH) analysis of sediment samples. In the current study, a combination of techniques including 'capillary racetrack' Purification and gradient cultivation resulted in the isolation of magnetotactic spirilla from aquatic sediments. Based on the 16S rRNA gene sequence analysis, the strain was identified as Magnetospirillum and was designated as Magnetospirillum sp. VITRJS1. The genes responsible for magnetosome formation (mamA, B, E, F, K, M, O, P, Q, T) were successfully detected using PCR amplification. The presence of cbbM gene confirmed that the isolate is chemolithoautotroph and utilises reduced sulphur as an electron source. Furthermore, magnetosomes extracted from VITRJS1 found to be cubo-octahedral in shape and 45 nm in size. Our results indicate that the systematic procedure using sediment analysis, CARD-FISH, and a combination of isolation methods enables the selective and rapid isolation of MTB from aquatic sediment sample. PMID- 27263005 TI - Homoharringtonine production by endophytic fungus isolated from Cephalotaxus hainanensis Li. AB - Homoharringtonine (HHT), a natural plant alkaloid derived from Cephalotaxus, has demonstrated to have a broad antitumor activity and efficacy in treating human chronic myeloid leukemia. An alternative source is required to substitute for the slow-growing and scarce Cephalotaxus to meet the increasing demand of the drug market. The objective of this study was to screen HHT-producing endophytic fungi from Cephalotaxus hainanensis Li. By screening 213 fungal isolates obtained from the bark parts of Cephalotaxus hainanensis Li, one isolate was found to be capable of biosynthesizing HHT. The fungus was identified as Alternaria tenuissima by morphological characteristics and internal transcribed spacer (ITS) sequence analysis and was named as CH1307. HHT obtained from CH1307 was analyzed through the HPLC and LC-MS/MS and NMR spectroscopy. The extract of the fermentation broth of CH1307 showed antiproliferative activities against K562 (chronic myelocytic leukemia), NB4 (acute promyelocytic leukemia), and HL-60 (promyelocytic leukemia) human cancer cell lines with IC50 values of 67.25 +/- 4.26, 65.02 +/- 4.75, and 99.23 +/- 4.26 MUg/mL, respectively. The findings suggest that HHT-producing endophytic fungus, Alternaria tenuissima CH1307 might provide a promising source for the research and application of HHT. PMID- 27263006 TI - Comparison between superficial and solid-state cultures of Isaria fumosorosea: conidial yields, quality and sensitivity to oxidant conditions. AB - Conidia production and quality from mycoinsecticides in solid-state cultures (SSC) are frequently inferred from superficial culture (SC) results. Both parameters were evaluated for two Isaria fumosorosea strains (ARSEF 3302 and CNRCB1), in SC and SSC, using culture media with the same chemical composition. For both strains, conidia production was higher in SC than SSC in terms of conidia per gram of dry substrate. Germination in both strains did not show significant differences between SC and SSC (>90 %). Similarly, conidia viability in ARSEF 3302 strain did not show differences at early stages between SC and SSC, but was higher in SC compared to SSC in the late stage of culture; in contrast, conidia from CNRCB1 strain did not differ between both culture systems. Some infectivity parameters improved in conidia from SSC, compared to SC at the early stages, but these differences disappeared at the final stage, independently of the strain. Both strains showed decreased conidia production when 26 % O2 pulses were applied; nevertheless, conidiation in SSC was two orders of magnitude more sensitive to oxidant pulses. In SC with 26 % O2 pulses, conidia viability for both strains at early stages, was higher than in normal atmospheric conditions. Infectivity towards Galleria mellonella larvae was similar between conidia from normal atmosphere and oxidant conditions; notably, for the strain ARSEF 3302 infectivity decreased at the final stage. This study shows the intrinsic differences between SC and SSC, which should be considered when using SC as a model to design production processes in SSC. PMID- 27263007 TI - Efficient hydroxylation of 1,8-cineole with monoterpenoid-resistant recombinant Pseudomonas putida GS1. AB - In this work, monoterpenoid hydroxylation with Pseudomonas putida GS1 and KT2440 were investigated as host strains, and the cytochrome P450 monooxygenase CYP176A1 (P450cin) and its native redox partner cindoxin (CinC) from Citrobacter braakii were introduced in P. putida to catalyze the stereoselective hydroxylation of 1,8 cineole to (1R)-6beta-hydroxy-1,8-cineole. Growth experiments in the presence of 1,8-cineole confirmed pseudomonads' superior resilience compared to E. coli. Whole-cell P. putida harboring P450cin with and without CinC were capable of hydroxylating 1,8-cineole, whereas coexpression of CinC has been shown to accelerate this bioconversion. Under the same conditions, P. putida GS1 produced more than twice the amount of heterologous P450cin and bioconversion product than P. putida KT2440. A concentration of 1.1 +/- 0.1 g/L (1R)-6beta-hydroxy-1,8 cineole was obtained within 55 h in shake flasks and 13.3 +/- 1.9 g/L in 89 h in a bioreactor, the latter of which corresponds to a yield YP/S of 79 %. To the authors' knowledge, this is the highest product titer for a P450 based whole-cell monoterpene oxyfunctionalization reported so far. These results show that solvent tolerant P. putida GS1 can be used as a highly efficient recombinant whole-cell biocatalyst for a P450 monooxygenase-based valorization of monoterpenoids. PMID- 27263008 TI - The pharmaceutics from the foreign empire: the molecular pharming of the prokaryotic staphylokinase in Arabidopsis thaliana plants. AB - Here, we present the application of microbiology and biotechnology for the production of recombinant pharmaceutical proteins in plant cells. To the best of our knowledge and belief it is one of few examples of the expression of the prokaryotic staphylokinase (SAK) in the eukaryotic system. Despite the tremendous progress made in the plant biotechnology, most of the heterologous proteins still accumulate to low concentrations in plant tissues. Therefore, the composition of expression cassettes to assure economically feasible level of protein production in plants remains crucial. The aim of our research was obtaining a high concentration of the bacterial anticoagulant factor-staphylokinase, in Arabidopsis thaliana seeds. The coding sequence of staphylokinase was placed under control of the beta-phaseolin promoter and cloned between the signal sequence of the seed storage protein 2S2 and the carboxy-terminal KDEL signal sequence. The engineered binary vector pATAG-sak was introduced into Arabidopsis thaliana plants via Agrobacterium tumefaciens-mediated transformation. Analysis of the subsequent generations of Arabidopsis seeds revealed both presence of the sak and nptII transgenes, and the SAK protein. Moreover, a plasminogen activator activity of staphylokinase was observed in the protein extracts from seeds, while such a reaction was not observed in the leaf extracts showing seed-specific activity of the beta-phaseolin promoter. PMID- 27263009 TI - Cloning of the cnr operon into a strain of Bacillaceae bacterium for the development of a suitable biosorbent. AB - In this study, a potential microbial biosorbent was engineered to improve its capacity to remediate heavy metal contaminated water resources. A Bacillaceae bacterium isolated from a mining area was transformed with a plasmid carrying the (pECD312)-based cnr operon that encodes nickel and cobalt resistance. The bioadsorption ability of the transformed strain was evaluated for removal of nickel from metallurgical water relative to the wildtype strain. Results showed that transformation improved the adsorption capacity of the bacterium by 37 % at nickel concentrations equivalent to 150 mg/L. Furthermore it was possible to apply prediction modelling to study the bioadsorption behaviour of the transformed strain. As such, this work may be extended to the design of a nickel bioremediation plant utilising the newly developed Bacillaceae bacterium as a biosorbent. PMID- 27263010 TI - Gut microbiota of Busseola fusca (Lepidoptera: Noctuidae). AB - Busseola fusca (Fuller) (Lepidoptera: Noctuidae) is a stemborer pest that attacks maize (Zea mays) throughout sub-Saharan Africa. Genetically modified maize has been shown to be effective against B. fusca. However, resistance of B. fusca against Bt-maize has developed and spread throughout South Africa. Previous studies suggested that gut microbiota contribute to mortality across a range of Lepidoptera. To fully assess the role of microbiota within the gut, it is essential to understand the microbiota harboured by natural B. fusca populations. This study aimed to identify the gut-associated bacteria by 16S rRNA gene sequencing. A total of 78 bacterial strains were characterised from the midgut of B. fusca larvae that were collected from 30 sites across the maize producing region of South Africa. Molecular phylogenetic analyses revealed bacteria affiliated to Proteobacteria, Actinobacteria, and Firmicutes. Taxonomic distribution placed these isolates into 15 different genera representing 20 species. The majority of bacteria identified belong to the genera Bacillus, Enterococcus, and Klebsiella. The B. fusca gut represents an intriguing and unexplored niche for analysing microbial ecology. The study could provide opportunities for developing new targets for pest management and contribute to understanding the phenomenon of resistance evolution of this species. PMID- 27263011 TI - Surface-attached and suspended bacterial community structure as affected by C/N ratios: relationship between bacteria and fish production. AB - Bacteria play crucial roles in the combined system of substrate addition and C/N control, which has been demonstrated to improve aquaculture production. However, the complexity of surface-attached bacteria on substrates and suspended bacteria in the water column hamper further application of this system. This study firstly applied this combined system into the culture of grass carp, and then explored the relationship between microbial complexes from surface-attached and suspended bacteria in this system and the production of grass carp. In addition, this study investigated bacterial community structures as affected by four C/N ratios using Illumina sequencing technology. The results demonstrated that the weight gain rate and specific growth rate of grass carp in the CN20 group (C/N ratio 20:1) were the highest (P < 0.05), and dietary supplementation of the microbial complex had positive effects on the growth of grass carp (P < 0.05). Sequencing data revealed that, (1) the proportions of Verrucomicrobiae and Rhodobacter (surface attached), sediminibacterium (suspended), and emticicia (surface-attached and suspended) were much higher in the CN20 group compared with those in the other groups (P < 0.05); (2) Rhodobacter, Flavobacterium, Acinetobacter, Pseudomonas, Planctomyces, and Cloacibacterium might be important for the microbial colonization on substrates; (3) as the C/N ratio increased, proportions of Hydrogenophaga (surface-attached and suspended), Zoogloea, and Flectobacillus (suspended) increased, but proportions of Bacillus, Clavibacter, and Cellvibro (surface-attached and suspended) decreased. In summary, a combined system of substrate addition and C/N control increased the production of grass carp, and Verrucomicrobiae and Rhodobacter in the surface-attached bacterial community were potential probiotic bacteria that contributed to the enhanced growth of grass carp. PMID- 27263012 TI - Modification and evaluation of the Carba NP test by use of paper strip for simple and rapid detection of carbapenemase-producing Enterobacteriaceae. AB - Carbapenemase-producing Enterobacteriaceae (CPE) isolates have now emerged worldwide. We therefore modified the phenotypic Carba NP test by use of a filter paper strip for easily and rapidly identifying CPE in routine laboratory. A collection of 56 CPE and carbapenemase-producing Pseudomonas spp. isolates (including 28 NDM-1, 11 IMP-14a, 1 IMP-1, 1 IMP-4, 1 IMP-9, 1 IMP-15, 4 VIM-2, 1 VIM-1, 1 IMP-14a with VIM-2, 3 OXA-48, 3 OXA-181 and 1 KPC-2 producers) and 41 non-CPE isolates (including 19 ESBL, 7 pAmpC, 3 AmpC, 9 ESBL with pAmpC and 3 non ESBL & non-AmpC producers) as confirmed by the PCR methods were tested by the paper strip method using pharmaceutical imipenem/cilastatin as a substrate. Bacterial colonies of each isolate were applied directly on filter paper strips dropped with either imipenem-phenol red (test strip) or phenol red solution alone (control strip). The reaction was read within 5 min. This test failed to detect 3 OXA-181, 2 OXA-48 and 3 IMP-14a producers (85.7 % sensitivity), whereas no false positives were seen (100 % specificity). Further evaluation of the paper strip test in 267 CPE screening-positive isolates from three hospitals by their medical technologists showed 92.0 % sensitivity (100 % for NDM producers) and 100 % specificity compared with the PCR methods. Because of its ease, rapidness and cost effective, the paper strip test has a potential for routine CPE testing in low-resource laboratories particularly in areas with high prevalence of NDM enzymes, leading to appropriate antimicrobial therapy and infection control strategy. PMID- 27263013 TI - Genetic characterization of Microcystis aeruginosa isolates from Portuguese freshwater systems. AB - Cyanobacteria are microorganisms that pose a serious threat to the aquatic waterways through the production of dense blooms under eutrophic conditions and the release of toxic secondary metabolites-cyanotoxins. Within cyanobacteria, the colonial planktonic Microcystis aeruginosa is widely distributed in both fresh and brackish aquatic environments throughout the world being frequently observed in the Portuguese water systems. Apart from the well-established distribution of M. aeruginosa in Portugal, knowledge of its genetic diversity and population structure is unknown. Therefore, in this study twenty-seven strains were obtained from the North, Centre and South regions of Portugal and were subjected to extensive phylogenetic analyses using simultaneously four distinct genetic markers (16S rRNA, 16S-23S ITS, DNA gyrase subunit beta and cell division protein (ftsZ)) encompassing in total 2834 bp. With this work we characterized the phylogenetic relationship among the Portuguese strains, with the southern strains showing higher genetic structure relatively to the North and Centre strains. A total of fifteen genotypes were determined for M. aeruginosa in Portuguese water systems revealing a high genetic diversity. This is also the first study to report geographic variation on the population structure of the Portuguese M. aeruginosa. PMID- 27263015 TI - Methylotrophic bacteria in sustainable agriculture. AB - Excessive use of chemical fertilizers to increase production from available land has resulted in deterioration of soil quality. To prevent further soil deterioration, the use of methylotrophic bacteria that have the ability to colonize different habitats, including soil, sediment, water, and both epiphytes and endophytes as host plants, has been suggested for sustainable agriculture. Methylotrophic bacteria are known to play a significant role in the biogeochemical cycle in soil ecosystems, ultimately fortifying plants and sustaining agriculture. Methylotrophs also improve air quality by using volatile organic compounds such as dichloromethane, formaldehyde, methanol, and formic acid. Additionally, methylotrophs are involved in phosphorous, nitrogen, and carbon cycling and can help reduce global warming. In this review, different aspects of the interaction between methylotrophs and host plants are discussed, including the role of methylotrophs in phosphorus acquisition, nitrogen fixation, phytohormone production, iron chelation, and plant growth promotion, and co inoculation of these bacteria as biofertilizers for viable agriculture practices. PMID- 27263014 TI - Fluorescent reporter systems for tracking probiotic lactic acid bacteria and bifidobacteria. AB - In the last two decades, there has been increasing evidence supporting the role of the intestinal microbiota in health and disease, as well as the use of probiotics to modulate its activity and composition. Probiotic bacteria selected for commercial use in foods, mostly lactic acid bacteria and bifidobacteria, must survive in sufficient numbers during the manufacturing process, storage, and passage through the gastro-intestinal tract. They have several modes of action and it is crucial to unravel the mechanisms underlying their postulated beneficial effects. To track their survival and persistence, and to analyse their interaction with the gastro-intestinal epithelia it is essential to discriminate probiotic strains from endogenous microbiota. Fluorescent reporter proteins are relevant tools that can be exploited as a non-invasive marker system for in vivo real-time imaging in complex ecosystems as well as in vitro fluorescence labelling. Oxygen is required for many of these reporter proteins to fluoresce, which is a major drawback in anoxic environments. However, some new fluorescent proteins are able to overcome the potential problems caused by oxygen limitations. The current available approaches and the benefits/disadvantages of using reporter vectors containing fluorescent proteins for labelling of bacterial probiotic species commonly used in food are addressed. PMID- 27263016 TI - Polysaccharide degradation systems of the saprophytic bacterium Cellvibrio japonicus. AB - Study of recalcitrant polysaccharide degradation by bacterial systems is critical for understanding biological processes such as global carbon cycling, nutritional contributions of the human gut microbiome, and the production of renewable fuels and chemicals. One bacterium that has a robust ability to degrade polysaccharides is the Gram-negative saprophyte Cellvibrio japonicus. A bacterium with a circuitous history, C. japonicus underwent several taxonomy changes from an initially described Pseudomonas sp. Most of the enzymes described in the pre genomics era have also been renamed. This review aims to consolidate the biochemical, structural, and genetic data published on C. japonicus and its remarkable ability to degrade cellulose, xylan, and pectin substrates. Initially, C. japonicus carbohydrate-active enzymes were studied biochemically and structurally for their novel polysaccharide binding and degradation characteristics, while more recent systems biology approaches have begun to unravel the complex regulation required for lignocellulose degradation in an environmental context. Also included is a discussion for the future of C. japonicus as a model system, with emphasis on current areas unexplored in terms of polysaccharide degradation and emerging directions for C. japonicus in both environmental and biotechnological applications. PMID- 27263018 TI - Carbon Nanohorns Promote Maturation of Neonatal Rat Ventricular Myocytes and Inhibit Proliferation of Cardiac Fibroblasts: a Promising Scaffold for Cardiac Tissue Engineering. AB - Cardiac tissue engineering (CTE) has developed rapidly, but a great challenge remains in finding practical scaffold materials for the construction of engineered cardiac tissues. Carbon nanohorns (CNHs) may be a potential candidate due to their special structure and properties. The purpose of this study was to assess the effect of CNHs on the biological behavior of neonatal rat ventricular myocytes (NRVMs) for CTE applications. CNHs were incorporated into collagen to form growth substrates for NRVMs. Transmission electron microscopy (TEM) observations demonstrated that CNHs exhibited a good affinity to collagen. Moreover, it was found that CNH-embedded substrates enhanced adhesion and proliferation of NRVMs. Immunohistochemical staining, western blot analysis, and intracellular calcium transient measurements indicated that the addition of CNHs significantly increased the expression and maturation of electrical and mechanical proteins (connexin-43 and N-cadherin). Bromodeoxyuridine staining and a Cell Counting Kit-8 assay showed that CNHs have the ability to inhibit the proliferation of cardiac fibroblasts. These findings suggest that CNHs can have a valuable effect on the construction of engineered cardiac tissues and may be a promising scaffold for CTE. PMID- 27263017 TI - Integrative computational approach for genome-based study of microbial lipid degrading enzymes. AB - Lipid-degrading or lipolytic enzymes have gained enormous attention in academic and industrial sectors. Several efforts are underway to discover new lipase enzymes from a variety of microorganisms with particular catalytic properties to be used for extensive applications. In addition, various tools and strategies have been implemented to unravel the functional relevance of the versatile lipid degrading enzymes for special purposes. This review highlights the study of microbial lipid-degrading enzymes through an integrative computational approach. The identification of putative lipase genes from microbial genomes and metagenomic libraries using homology-based mining is discussed, with an emphasis on sequence analysis of conserved motifs and enzyme topology. Molecular modelling of three-dimensional structure on the basis of sequence similarity is shown to be a potential approach for exploring the structural and functional relationships of candidate lipase enzymes. The perspectives on a discriminative framework of cutting-edge tools and technologies, including bioinformatics, computational biology, functional genomics and functional proteomics, intended to facilitate rapid progress in understanding lipolysis mechanism and to discover novel lipid degrading enzymes of microorganisms are discussed. PMID- 27263019 TI - Prospective assessment of perioperative course in 2648 patients after surgical treatment of benign prostatic obstruction. AB - PURPOSE: TUR-prostate (TUR-P) is considered the reference method for surgical treatment of benign prostatic obstruction (BPO); Greenlight laser photoselective vaporization (PVP) and thulium laser vapoenucleation (ThuVEP) have also been established as treatments of BPO. Objective of this prospective observation was to compare a large numbers of patients treated in everyday routine. METHODS: This prospective multicentre data collection assesses morbidity and perioperative course of consecutive men treated with BPO-related transurethral surgery between 2011 and 2014 in a German metropolis area with TUR-P, PVP or ThuVEP. RESULTS: Two thousand six hundred and forty-eight patients have been treated in the time period. All treatment options achieved immediate improvement of voiding parameters. Multivariate analyses proved shorter hospital stay after laser treatments as compared to resection (p < 0.001). In terms of hospital stay, the advantage of ThuVEP compared to TUR-P increased with prostate volume (p < 0.001). Patients with ongoing anticoagulation or bridging had prolonged hospital stay (p < 0.001). Overall adverse events were least frequent in PVP (p 0.016), as were Clavien 3b events (p < 0.001). CONCLUSIONS: Surgical treatment of BPO is effective and safe independent of the surgical procedure. Volume reduction is most effective in ThuVEP; PVP has the lowest rate of severe complications. Laser treatment is associated with shorter hospital stay. Surgery under ongoing anticoagulation prolonged the post-operative hospital stay. PMID- 27263020 TI - Mycophenolate mofetil in steroid-dependent idiopathic nephrotic syndrome. AB - BACKGROUND: Prospective studies have established the mycophenolate mofetil (MMF) efficiency in childhood idiopathic nephrotic syndrome (INS) but reports on the long-term outcome are lacking. Moreover, the search for factors influencing its efficiency would be useful to define its place among the other treatments. METHODS: We performed a monocentric retrospective study including 96 children with steroid-dependent INS followed for 4.7 years (median) (IQ 3-6) after the onset of MMF treatment. The characteristics of responder patients (n = 74), as defined by a 50 % decrease of relapse rate and/or a 60 % decrease of steroid dose, and of non-responder patients (n = 22) were compared by univariate analysis and multivariate logistic regression. RESULTS: Withdrawal of prednisone was achieved in 48/96 patients after a median duration of 18.1 months (IQ 7.8-30.0) of MMF. Only 26/48 patients did not relapse under MMF alone. After MMF was stopped in these patients, only six remained in remission without any treatment at last follow-up. Responders had a shorter time to remission at the first flare (9.5 vs. 15 days, p = 0.02), a shorter disease duration prior to the onset of MMF (22.2 vs. 94.5 months, p = 0.001), and were younger at the MMF initiation (6.7 vs. 10.1 years, p = 0.02) than non-responder patients. The age of MMF initiation was an independent factor associated with efficiency (OR = 0.80, 95 % CI [0.69, 0.93], p < 0.01). CONCLUSIONS: MMF is more efficient in young patients treated early in the disease course. Nevertheless, MMF has no remnant effect while nearly all patients relapsed after withdrawal of the drug. PMID- 27263022 TI - Transglutaminase 2 and Transglutaminase 2 Autoantibodies in Celiac Disease: a Review. AB - Celiac disease is a common inflammatory disorder with a prevalence of 1-2 % in which a distinct dietary wheat, rye, and barley component, gluten, induces small bowel mucosal villous atrophy, crypt hyperplasia, and inflammation. The small bowel mucosal damage can be reversed by a strict lifelong gluten-free diet, which is currently the only effective treatment for the condition. A key player in the pathogenetic process leading to the enteropathy is played by a protein called transglutaminase 2 (TG2), which is able to enzymatically modify gluten-derived gliadin peptides. The TG2-catalyzed deamidation of the gliadin peptides results in their increased binding affinity to the disease-predisposing human leukocyte antigen (HLA) DQ2 and DQ8 molecules, thus enabling a strong immune response to be launched. Blocking the enzymatic activity of TG2 has thus been suggested as a suitable novel pharmacological approach to treat celiac disease. By virtue of its transamidation capacity, TG2 is also able to cross-link gliadin peptides to itself, this resulting in the generation of TG2-gliadin peptide complexes whose presence might provide an explanation for the generation of the TG2 autoantibodies characteristic of celiac disease. Due to their excellent specificity for the disorder, the TG2-targeted autoantibodies are widely used in the diagnostics as a first-line test to select patients for gastrointestinal endoscopy. More recently, it has come to be appreciated that these autoantibodies and also the TG2-specific B cells might play an active role in the disease pathogenesis. In this review, we assess the role of TG2, TG2-specific B cells, and autoantibodies in celiac disease. PMID- 27263021 TI - Association of blood pressure variability and neurocognition in children with chronic kidney disease. AB - BACKGROUND: Children with chronic kidney disease (CKD) and hypertension have increased blood pressure variability (BPV), which has been associated with lower neurocognitive test scores in adults. Children with CKD are at risk for decreased neurocognitive function. Our objective was to determine whether children with CKD and increased BPV had worse performance on neurocognitive testing compared with children with CKD and lower BPV. METHODS: This was a cross-sectional and longitudinal analysis of the relation between BPV and neurocognitive test performance in children >=6 years enrolled in the Chronic Kidney Disease in Children (CKiD) study. Visit-to-visit BPV was assessed by the standard deviation of visit BPs (BPV-SD) and average real variability (ARV). Ambulatory BPV was assessed by SD of wake and sleep periods on 24-h ambulatory BP monitoring. RESULTS: We assessed 650 children with a mean follow-up period of 4.0 years. Children with systolic visit-to-visit BPV in the upper tertile had lower scores on Delis-Kaplan Executive Function System (D-KEFS) Verbal Category Switching than those with BPV in the lower tertile (BPV-SD, 8.3 vs. 9.5, p = 0.006; ARV, 8.5 vs. 9.6, p = 0.02). On multivariate analysis, the association between lower Category Switching score and increased BPV remained significant after controlling for mean BP, demographic characteristics, and disease-related variables [BPV-SD, beta = 0.7, 95 % confidence interval (CI) -1.28 to -0.12; ARV, beta = -0.54, CI -1.05 to -0.02). Ambulatory BPV was not independently associated with any cognitive measure. CONCLUSIONS: Higher systolic visit-to-visit BPV was independently associated with decreased D-KEFS Category Switching scores in children with mild to-moderate CKD. PMID- 27263023 TI - Streptomyces bryophytorum sp. nov., an endophytic actinomycete isolated from moss (Bryophyta). AB - A novel endophytic actinomycete, designated strain NEAU-HZ10(T) was isolated from moss and characterised using a polyphasic approach. The strain was found to have morphological and chemotaxonomic characteristics typical of the genus Streptomyces. Strain NEAU-HZ10(T) formed grayish aerial mycelia, which differentiated into straight to flexuous chains of cylindrical spores. The cell wall peptidoglycan was found to contain LL-diaminopimelic acid. Predominant menaquinones were identified as MK-9(H6) and MK-9(H8). The polar lipid profile was found to consist of phosphatidylethanolamine, phosphatidylinositol and two unidentified phospholipids. The major fatty acids were identified as iso-C16:0, anteiso-C15:0 and C16:0. 16S rRNA gene sequence similarity studies showed that strain NEAU-HZ10(T) belongs to the genus Streptomyces and exhibits high sequence similarity to Streptomyces cocklensis DSM 42063(T) (98.9 %). Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain NEAU-HZ10(T) clustered with S. cocklensis DSM 42063(T), Streptomyces yeochonensis CGMCC 4.1882(T) (98.7 %), Streptomyces paucisporeus CGMCC 4.2025(T) (98.4 %) and Streptomyces yanglinensis CGMCC 4.2023(T) (98.1 %). However, a combination of DNA DNA hybridisation results and some phenotypic characteristics indicated that strain NEAU-HZ10(T) can be distinguished from its phylogenetically closely related strains. Therefore, it is proposed that strain NEAU-HZ10(T) represents a novel species of the genus Streptomyces for which the name Streptomyces bryophytorum sp. nov. is proposed. The type strain is NEAU-HZ10(T) (= CGMCC 4.7151(T) = DSM 42138(T)). PMID- 27263024 TI - Solving shortage in a priceless market: Insights from blood donation. AB - Shortage is common in many markets, such as those for human organs or blood, but the problem is often difficult to solve through price adjustment, given safety and ethical concerns. In this paper, we study two non-price methods that are often used to alleviate shortage for human blood. The first method is informing existing donors of a current shortage via a mobile message and encouraging them to donate voluntarily. The second method is asking the patient's family or friends to donate in a family replacement (FR) program at the time of shortage. Using 447,357 individual donation records across 8 years from a large Chinese blood bank, we show that both methods are effective in addressing blood shortage in the short run but have different implications for total blood supply in the long run. We compare the efficacy of these methods and discuss their applications under different scenarios to alleviate shortage. PMID- 27263025 TI - Direct imaging of elemental distributions in tissue sections by laser ablation mass spectrometry. AB - We present a strategy for imaging of elements in biological tissues using laser ablation (LA) mass spectrometry (MS), which was compared to laser ablation inductively coupled plasma (LA-ICP) MS. Both methods were adopted for quantitative imaging of elements in mouse kidney, as well as traumatic brain injury model tissue sections. MS imaging (MSI) employing LA provides quantitative data by comparing signal abundances of sodium from tissues to those obtained by imaging quantitation calibration standards of the target element applied to adjacent control tissue sections. LA-ICP MSI provided quantitative data for several essential elements in both brain and kidney tissue sections using a dried droplet approach. Both methods were used to image a rat model of traumatic brain injury, revealing accumulations of sodium and calcium in the impact area and its peripheral regions. LA MSI is shown to be a viable option for quantitative imaging of specific elements in biological tissue sections. PMID- 27263026 TI - Quantifying autophagy: Measuring LC3 puncta and autolysosome formation in cells using multispectral imaging flow cytometry. AB - The use of multispectral imaging flow cytometry has been gaining popularity due to its quantitative power, high throughput capabilities, multiplexing potential and its ability to acquire images of every cell. Autophagy is a process in which dysfunctional organelles and cellular components that accumulate during growth and differentiation are degraded via the lysosome and recycled. During autophagy, cytoplasmic LC3 is processed and recruited to the autophagosomal membranes; the autophagosome then fuses with the lysosome to form the autolysosome. Therefore, cells undergoing autophagy can be identified by visualizing fluorescently labeled LC3 puncta and/or the co-localization of fluorescently labeled LC3 and lysosomal markers. Multispectral imaging flow cytometry is able to collect imagery of large numbers of cells and assess autophagy in an objective, quantitative, and statistically robust manner. This review will examine the four predominant methods that have been used to measure autophagy via multispectral imaging flow cytometry. PMID- 27263027 TI - [Abortion Internet searches. An evaluation with Google Trends in Peru]. PMID- 27263028 TI - [Times of gender equity: a description of the inequalities between autonomous communities, Spain 2006-2014]. AB - OBJECTIVE: Gender equity (GE) is a structural determinant of health inequalities. In this light, our objective is to show the evolution of gender equity in the Spanish autonomous communities since 2006, prior to the enactment of the Equality Act (2007) and the economic crisis (2008), until 2014. METHOD: Ecological study of gender equity in the 17 Spanish autonomous communities from 2006-2011-2014. We have calculated: 1) modified gender equity index (MGEI) for the autonomous communities (0=equity, +/-1=inequity); 2) interregional and temporal convergences in gender equity. RESULTS: The MGEI in the autonomous communities in 2014 has negative values close to 0 (inequity towards women). There is no interregional convergence due to the dispersion increase (2006: 0.1503; 2011: 0.2280; 2014: 0.4964), and no temporal convergence due to the lack of progress of the autonomous communities with poor gender equity. The gender gap in economic activity continues to be unfavourable to women, decreasing in all communities between 2006 and 2011 but increasing in six communities in 2014. The gender gap in education from 2006-2011-2014 has positive values close to 0 (unfavourable to men), while the gender gap in empowerment is unfavourable to women, representing the most significant gender equity disparity. Inter-community dispersion of economic activity and education did not change between 2006 and 2014, while inter community dispersion of empowerment increased. CONCLUSIONS: The level of gender equity achieved in the Spanish autonomous communities in 2006 was lost during the economic crisis, as gender equity disparities between the communities had increased by 2014. Gender inequity continues to be unfavourable to women. PMID- 27263029 TI - Previously unknown species of Aspergillus. AB - The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology based identification of Aspergillus remains limited to the section or species complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. PMID- 27263030 TI - Are hantavirus infections also part of the rapidly growing spectrum of an infection-triggered reactive haemophagocytic syndrome? PMID- 27263031 TI - Simultaneous wireless assessment of intra-oral pH and temperature. AB - OBJECTIVES: Intra-oral pH plays an important role in the pathogenesis of tooth erosion and decay, but there is limited information about its variation in real life settings. The aims of this research were to: 1) develop a wireless device, which can be used to continuously monitor intra-oral pH and temperature in real time; 2) test and validate the device under controlled laboratory conditions; and 3) collect data in a natural environment in a sample of healthy volunteers. METHODS: A wireless device for measuring pH and temperature simultaneously was developed, calibrated and validated against the gold standard glass electrode pH meter. A smart phone was used as data logger. The wireless device was embedded in an oral appliance and worn by eleven participants (mean age 31.1+/-6.9years) for 24h, while conducting standardised drinking tasks and regular daily activities. RESULTS: The wireless device could accurately measure pH and temperature both in vitro and in vivo. The recovery time following the swallow of a standard acidic drink varied markedly among individuals (mean=1.3+/-0.9min). The intra-oral pH and temperature recorded in the natural environment also showed a large inter- and intra-individual variability. The average intra-oral pH when asleep (6.7+/ 0.5) was lower (p<0.001) than when awake (7.2+/-0.5). The average intra-oral temperature during sleep (35.6+/-0.5 degrees C) was higher (p<0.001) than when awake (34.5+/-0.7 degrees C). CONCLUSIONS: Intra-oral pH and temperature can be continuously and wirelessly assessed in real-life settings, and show individual specific patterns with circadian variations. Intra-oral pH becomes slightly acidic during sleep while intra-oral temperature increases and fluctuates less. CLINICAL SIGNIFICANCE: We propose a wireless device that is capable of measuring intra-oral pH over a 24-h period. We found marked inter-individual variation after acidic stimuli, and day to sleep time variation of both intra-oral temperature and pH. Our approach may provide new insight into the relationship between oral pH, tooth wear and decay. PMID- 27263032 TI - Clinical outcomes of different types of tooth-supported bilayer lithium disilicate all-ceramic restorations after functioning up to 5 years: A retrospective study. AB - OBJECTIVES: The aim of this retrospective study with large sample was to assess the 5-year clinical outcomes of four different types of restorations made from IPS e.max Press. METHODS: A total of 6855 restorations containing veneers (Vs), single crowns (SCs), 2-unit or multiple-unit combined crowns (CCs) and 3-unit or multiple-unit fixed dental prostheses (FDPs) from 4634 patients were included. Data collection were performed through scrutiny and registration of the records of all patients. The cumulative survival rates (CSRs) and their differences were calculated according to the Kaplan-Meier analysis and Log-Rank test. The differences among the failure rates of different restorations were evaluated according to the Chi-squared test. RESULTS: The 5-year CSR of all restorations was 96.6%. The 5-year CSRs of CCs (94.4%) and FDPs (90.6%) were both significantly lower than those of SCs (96.5%) and Vs (97.2%). A total failure rate was 3.2%. The failure rate of FDPs was 9.0%, which was significantly higher than those of Vs (2.5%) and SCs (3.3%), and was similar to that of CCs (5.2%). The failure rate of molar SCs (8.2%) was significantly higher than those of anterior (3.2%) and premolar SCs (2.5%). 83.0% of failed restorations happened in the 1st year after cementation and 50.6% happened in the first 3 months. Moreover, ceramic chipping (41.5%) and fracture (37.3%) were the top two reasons. In anterior tooth region, the ceramic damage rate of Vs (1.7%) was significantly lower than those of FDPs (8.1%) and CCs (4.8%), and that of SCs (2.6%) was significantly lower than that of FDPs (8.1%). CONCLUSION: IPS e.max Press has an ideal medium-term outcome. The failures mainly occurred in the first 3 months after cementation and the main reasons were ceramic chipping and fracture. Due to higher failure risk, we suggest dentists should be cautious to apply FDPs, CCs and molar SCs. PMID- 27263033 TI - Sex-Related Differences in Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage. AB - BACKGROUND: Several population-based studies found a higher case fatality after aneurysmal subarachnoid hemorrhage (ASAH) in women than in men. This may relate to differences in prognostic characteristics. We therefore assessed sex differences in prognosticators and outcome in ASAH patients. METHODS: From a prospectively collected ASAH database, we retrieved data on patients admitted from 1990 to 2010. We calculated prevalence ratios (PRs) with corresponding 95% confidence intervals (CIs) for prognosticators (clinical condition on admission, site and treatment of the aneurysm, and complications during the clinical course) and risk ratios (RRs) for in-hospital death and poor outcome (death or dependence) at 3 months. RRs were adjusted for possible confounding with Poisson regression analysis. RESULTS: Of the 1761 included patients, 1211 (68.8%) were women, who were 1.9 (95% CI: .5<->3.3) years older than men. PRs for women for the site of the aneurysm were 1.71 (95% CI: 1.38<->2.13) for the carotid artery, .68 (95% CI: .60<->.77) for the anterior communicating artery, 1.14 (95% CI: .92< >1.41) for the middle cerebral artery, and .85 (95% CI: .63<->1.13) for posterior circulation. PRs of other prognosticators were similar between sexes. The crude RR for in-hospital death for women was .91 (95% CI: .78<->1.05) and for poor outcome at 3 months was .95 (95% CI: .85<->1.06); both remained similar after adjustment. CONCLUSIONS: In this study, in-hospital death and poor outcome at 3 months did not differ between men and women. Women were slightly older than men and had different distributions of aneurysm sites, but not to an extent that it explained a sex difference in outcome. PMID- 27263034 TI - Design and Rationale for a Cognitive Outcome Substudy in Ischemic Stroke Patients with High Risk of Cerebral Hemorrhage. AB - GOAL: Cognitive impairment and dementia are common disabilities after stroke and are associated with increased risks of mortality and recurrent stroke. The prevention of dementia and preserving cognitive function are also important in stroke patients, but its strategy is not established yet. This PICASSO-COG (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage for reducing COGnitive decline) substudy aims to assess the effects of cilostazol and/or probucol on cognitive function. MATERIALS AND METHODS: The substudy aims to assess the reduction in cognitive decline of patients treated with cilostazol and/or probucol in the PICASSO trial. Patients will be assessed using the Korean version of mini-mental state examination and Montreal Cognitive Assessment at 4, 7, 10, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mini-mental status examination score, compared between treatment groups, with a modified intention to-treat population using a restricted maximum likelihood-based mixed effects model repeat measurement. This will allow a within-subject correlation due to repeated cognitive tests as well as a different number of measurements among subjects at baseline and each follow-up period. CONCLUSION: PICASSO-COG is a novel study for assessing the effect on cognitive function of different antiplatelet regimens and the addition of a nonstatin lipid-lowering agent to the current standard statin therapy in patients who have a recent ischemic lesion and prior intracerebral macro- or microbleeds. PMID- 27263035 TI - Correlation of the L-Arginine Pathway with Thrombo-Inflammation May Contribute to the Outcome of Acute Ischemic Stroke. AB - BACKGROUND: Immune responses contribute to secondary injury after acute ischemic stroke (AIS), and metabolites of the L-arginine pathway are associated with stroke outcome. Here, we analyzed the relationship of the L-arginine pathway with thrombo-inflammatory biomarkers in AIS and their additive and independent associations to outcome. METHODS: Serial changes in P-selectin, tPA, MCP-1, sCD40L, IL-6, IL-8, L-arginine, and asymmetric and symmetric dimethylarginine (ADMA, SDMA) were investigated in 55 patients with AIS and without infection within 6 and 72 hours after stroke onset. Outcomes were assessed as National Institutes of Health Stroke Scale (NIHSS) worsening by 24 hours, poststroke infection, and death by 1 month. RESULTS: Serum levels of L-arginine showed negative correlation, whereas ADMA and SDMA showed positive correlation with thrombo-inflammatory biomarkers in the hyperacute phase. Most of these correlations disappeared by 72 poststroke hours. Correlation of MCP-1 with both ADMA and SDMA levels at 6 hours was associated with both NIHSS worsening and poststroke infections, respectively; sCD40L and SDMA correlation at 6 hours was also associated with NIHSS worsening. Negative correlation between P-selectin and L-arginine concentrations in the hyperacute phase was associated with NIHSS worsening. Strong negative correlation was found between IL-6 and L-arginine levels in the hyperacute phase in patients with poststroke infection. Only L arginine and SDMA at 72 hours were independently associated with poststroke infection respectively. CONCLUSIONS: Concentration of L-arginine and ADMA/SDMA differentially correlates with thrombo-inflammation in the hyperacute phase of ischemic stroke. Such correlations are independently associated with poststroke infection but not with other outcomes. PMID- 27263036 TI - Effects of novel subtype selective M-current activators on spinal reflexes in vitro: Comparison with retigabine. AB - The activation of Kv7 channels and the resulting M-current is a powerful mechanism to control neuronal excitability with profound effects in pain pathways. Despite the lack of specific data on the expression and role of these channels in nociceptive processing, much attention has been paid at exploring their potential value as targets for analgesia. Here we have characterized the spinal actions of two novel subunit selective Kv7 activators, ICA-069673 and ML213, and compared their effects to those of retigabine that acts with similar affinity on all neuronal Kv7 channels. Spinal reflexes were recorded in a mouse spinal cord in vitro preparation to allow the testing of the compounds on native spinal pathways at known concentrations. As retigabine, novel compounds depressed spinal segmental transmission with particularly strong effects on wind up, showing an adequate pro-analgesic profile. ML213 presented the highest potency. In contrast to retigabine, the effects of ICA-069673 and ML213 were blocked by XE 991 even at the highest concentrations used, suggesting specific effect on Kv7 channels. In addition, the effects of ICA-069673 on repetitive stimulation are consistent with a mode of action involving state or activity dependent interaction with the channels. Compared to retigabine, novel Kv7 openers maintain strong depressant effects on spinal nociceptive transmission showing an improved specificity on Kv7 channels. The differential effects obtained with these Kv7 openers may indicate the existence of several Kv7 conformations in spinal circuits. PMID- 27263037 TI - mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus. AB - Epilepsy is a major risk factor for autism spectrum disorder (ASD) and complicates clinical manifestations and management of ASD significantly. Tuberous sclerosis complex (TSC), caused by TSC1 or TSC2 mutations, is one of the medical conditions most commonly associated with ASD and has become an important model to examine molecular pathways associated with ASD. Previous research showed reversal of autism-like social deficits in Tsc1 +/- and Tsc2 +/- mouse models by mammalian target of rapamycin (mTOR) inhibitors. However, at least 70 % of individuals with TSC also have epilepsy, known to complicate the severity and treatment responsiveness of the behavioural phenotype. No previous study has examined the impact of seizures on neurocognitive reversal by mTOR inhibitors. Adult Tsc2 +/- (Eker)-rats express social deficits similar to Tsc2 +/- mice, with additive social deficits from developmental status epilepticus (DSE). DSE was induced by intraperitoneal injection with kainic acid at post-natal days P7 and P14 (n = 12). The experimental group that modelled TSC pathology carried the Tsc2 +/- (Eker)-mutation and was challenged with DSE. The wild-type controls had not received DSE (n = 10). Four-month-old animals were analysed for social behaviour (T1), then treated three times during 1 week with 1 mg/kg everolimus and finally retested in the post-treatment behavioural analysis (T2). In the experimental group, both social interaction and social cognition were impaired at T1. After treatment at T2, behaviour in the experimental group was indistinguishable from controls. The mTOR inhibitor, everolimus, reversed social deficit behaviours in the Tsc2 haploinsufficiency plus DSE animal model to control levels. PMID- 27263039 TI - Combined hormonal contraceptive use among obese women and risk for cardiovascular events: A systematic review. AB - CONTEXT: Combined hormonal contraceptive (CHC) use may modify the risk of cardiovascular events in obese [body mass index (BMI) >=30kg/m2] women. OBJECTIVE: The objective was to evaluate from the literature whether CHC use modifies the risk of acute myocardial infarction (AMI), stroke, cerebral venous thrombosis (CVT) and venous thromboembolism (VTE) in obese women and to evaluate evidence for a dose-response relationship between BMI and VTE. METHODS: We searched PubMed for all articles published between database inception and February 2016 providing direct evidence on BMI, CHCs, and cardiovascular outcomes. We also searched for indirect evidence related to a dose-response relationship between BMI and risk of VTE in the general population, as these data were lacking for CHC users. The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. RESULTS: The direct evidence search yielded 3 pooled analyses, 11 case-control studies and 1 cohort study. There was conflicting evidence about the risk of AMI or stroke among obese combined oral contraceptive (COC) users compared to obese nonusers, with one study finding no increased risk for AMI or stroke for COC users overall or stratified by BMI. A second study found significantly increased risk of AMI and stroke for COC users, with the highest risk estimates for high-BMI COC users. A single study suggested that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. For VTE, obese COC users consistently had a risk that was 5 to 8 times that of obese nonusers and approximately 10 times that of nonobese nonusers. Five prospective cohort studies were identified as indirect evidence, and all found increased risk for VTE as BMI increased, suggesting a dose-response relationship between BMI and risk for VTE. No studies on the contraceptive patch or vaginal ring were identified that met the inclusion criteria. CONCLUSION: Limited evidence of Level II-2, fair quality, concerning whether CHC use modifies the risk of AMI and stroke in obese women is inconclusive, while a single study of Level II-2, poor quality, found that obese COC users may be at higher risk for CVT compared with normal-weight nonusers. Both COC use and higher BMI increase risk for VTE, and the greatest relative risks are for those with both risk factors based on a body of evidence graded as Level II-2, fair to poor quality. It is not possible to estimate absolute risk of VTE among women with both of these risk factors; however, the absolute risk of VTE in healthy women of reproductive age is small. PMID- 27263040 TI - Questions to the LASS study group. PMID- 27263038 TI - Ultrasonographic risk factors of malignancy in thyroid nodules. AB - INTRODUCTION: Between 40 and 50 % of the population will have at least one thyroid nodule, although only 5-8 % will have a malignant one. OBJECTIVE: The objective of this study was to establish the ultrasonographic characteristics which allow us to distinguish benignity from malignancy in thyroid nodules. METHODS: In the study population, inclusion criteria are (1) a single thyroid nodule and (2) multinodular goiter and exclusion criteria are (1) previous thyroid surgery and (2) fine needle aspiration (FNA) in the past month. This study is a double-blind prospective study. The study protocol is as follows: (1) clinical study; (2) ultrasound examination; (3) FNA; and (4) surgery-follow-up. The variables analysed are as follows: a multinodular nodule or goitre; colloid degeneration; morphology; margins; hyperechoic rim; rim thickness; rim morphology; size; angle between the major axis and the skin; echostructure; posterior acoustic findings; calcifications; thick colloid; localization of the intrathyroid nodular tissue; and characteristics in the Doppler scan. RESULTS: A total of 221 thyroid nodules were analysed. The following ultrasound findings were associated with malignancy (p < 0.05): a nodule with posterior acoustic shadowing; the echotexture of the nodule; intranodular colloid degeneration; nodule margins; nodular morphology; the presence of thick colloid; the angle between the major axis and the skin; characteristics of the intranodular vessels using color Doppler and Doppler energy; and calcifications. In the multivariate analysis, the following factors persisted as predictors of malignancy: the echotexture of the nodule (odds ratio 12.81), microcalcifications (OR 9.05), and chaotic vascularisation in the Doppler energy (OR 43.47). CONCLUSIONS: The high resolution ultrasound allowed for a more reliable diagnosis of malignancy. The main findings of malignancy were the hypoechogenicity echotexture, microcalcifications, and chaotic intranodular vessels using Doppler energy. PMID- 27263041 TI - The safety of intrauterine contraception initiation among women with current asymptomatic cervical infections or at increased risk of sexually transmitted infections. AB - OBJECTIVE: The objective was to assess risk of pelvic inflammatory disease (PID) among women with current asymptomatic undiagnosed cervical infection or who are at high risk of sexually transmitted infections (STIs), comparing those who have a copper-bearing (Cu-) or levonorgestrel (LNG-) intrauterine device (IUD) placed with women who do not. STUDY DESIGN: We searched PubMed and Cochrane Library for articles from January 1984 through January 2016 addressing our objective. We assessed study quality using the United States Preventive Services Task Force evidence grading system. RESULTS: Our search strategy yielded 2220 articles, of which 10 met inclusion criteria. Two studies provided direct evidence of PID rates in women with undiagnosed gonococcal or chlamydial (GC/CT) infection or at high risk for STIs initiating IUDs versus other contraceptive methods (level II 2, fair to poor), and neither study found a difference. Eight studies provided indirect evidence (II-2 to II-3, fair to poor). One study found no difference in PID rates between initiators of Cu- versus LNG-IUDs. Five studies compared algorithms based on patient factors with laboratory GC/CT screening to predict cervical infection. Based on likelihood ratios, none of these algorithms adequately identified women at high risk of asymptomatic cervical infection who should not undergo IUD placement. Two studies compared IUD placement on the same day as STI screening with delayed placement after screening and found no difference in PID rates. CONCLUSION: Limited evidence suggests that IUD placement does not increase the risk of PID compared with no IUD placement among women with asymptomatic undiagnosed cervical infection or at high risk of STIs. Algorithms based on patient characteristics to identify women with asymptomatic GC/CT may be overly restrictive, leading to missed opportunities for IUD initiation. Historical concerns about higher PID risk among women at risk for STIs who use IUDs may not be relevant with modern devices and STI screening and treatment practices. PMID- 27263042 TI - Reply to letter to the editor: "questions to the LASS study group". PMID- 27263043 TI - Misoprostol before first trimester surgical abortion: a patient-centered approach. PMID- 27263044 TI - Routine misoprostol before all surgical abortions. PMID- 27263045 TI - Can cycling safety be improved by opening all unidirectional cycle paths for cycle traffic in both directions? A theoretical examination of available literature and data. AB - Many studies have found bicycle-motor vehicle crashes to be more likely on bidirectional cycle paths than on unidirectional cycle paths because drivers do not expect cyclists riding at the right side of the road. In this paper we discuss the hypothesis that opening all unidirectional cycle paths for cycle traffic in both directions prevent this lack of expectancy and accordingly improves cycling safety. A new national standard requires careful consideration because a reversal is difficult once cyclists are used to their new freedom of route choice. We therefore explored the hypothesis using available data, research, and theories. The results show that of the length of cycle paths along distributor roads in the Netherlands, 72% is bidirectional. If drivers would become used to cyclists riding at the left side of the road, this result raises the question of why bidirectional cycle paths in the Netherlands still have a poor safety record compared to unidirectional cycle paths. Moreover, our exploration suggested that bidirectional cycle paths have additional safety problems. It increases the complexity of unsignalized intersections because drivers have to scan more directions in a short period of time. Moreover, there are some indications that the likelihood of frontal crashes between cyclists increases. We reject the hypothesis that opening all unidirectional cycle paths for cycle traffic in both directions will improve cycle safety. We recommend more attention for mitigating measures given the widespread application of bidirectional cycle paths in the Netherlands. PMID- 27263046 TI - Non-vitamin K antagonist oral anticoagulants for the prevention of recurrent venous thromboembolism. AB - Venous thromboembolism (VTE) is associated with a risk of recurrence that depends on factors specific to index event and patient. A first unprovoked VTE increases the risk of a recurrent event, particularly during the first year after anticoagulation cessation. Determining a strategy for the long-term prevention of recurrent VTE poses challenges that stem from a lack of agreement on recommended therapy duration and varying treatment burden for the patient. Oral anticoagulants, including vitamin K antagonists and non-vitamin K antagonist oral anticoagulants (NOACs), are the main treatment options for the long-term prevention of recurrent VTE. However, the risk of VTE recurrence must be balanced against the risk of bleeding in each patient. Phase III clinical trials have evaluated rivaroxaban, apixaban and dabigatran for extended treatment and prevention of VTE versus placebo, and versus warfarin in the case of dabigatran. Compared with placebo treatment, each NOAC showed superior efficacy together with an acceptable safety profile during extended treatment periods of 6-18months. Patients receiving long-term NOAC therapy will still require regular risk factor assessment, but these agents may permit longer treatment duration with an improved benefit-risk profile. PMID- 27263047 TI - Prognostic Effect of Low Subcutaneous Adipose Tissue on Survival Outcome in Patients With Multiple Myeloma. AB - BACKGROUND: Increasing evidence suggests that decreased skeletal muscle mass (sarcopenia) or adipose tissue assessed using computed tomography (CT) predicts negative outcomes in patients with solid tumors. However, the prognostic value of such an assessment in multiple myeloma (MM) remains unknown. PATIENTS AND METHODS: Consecutive patients with newly diagnosed symptomatic MM were retrospectively analyzed. The cross-sectional area of skeletal muscles and subcutaneous or visceral adipose tissue was measured using CT. Body composition indexes (skeletal muscle index, subcutaneous adipose tissue index [SAI], and visceral adipose tissue index) were calculated. The association between these indexes and overall survival (OS) was examined. RESULTS: Of 56 evaluable patients, 37 (66%) had sarcopenia. The 2-year OS in patients with SAI < median was 58% compared with 91% in those with SAI >= median (P = .006). In multivariate analyses, SAI < median was significantly associated with poor OS (hazard ratio, 4.05; P = .02). Sarcopenia was not associated with OS. The maximum value of the standardized uptake value was significantly higher in patients with SAI < median (P = .02). CONCLUSION: The findings of this study suggest that low subcutaneous adipose tissue at baseline predicts poor survival outcome in patients with MM. PMID- 27263048 TI - The Ionic Products from Mineral Trioxide Aggregate-induced Odontogenic Differentiation of Dental Pulp Cells via Activation of the Wnt/beta-catenin Signaling Pathway. AB - INTRODUCTION: Mineral trioxide aggregate (MTA) has been successfully used in clinical applications in endodontics. However, little is known about the involvement of Wnt/beta-catenin signaling in human dental pulp cells (hDPC) differentiation with the interaction of MTA in hard tissue regeneration, especially in odontogenesis. Therefore, the aim of this study was to explore odontogenic/osteogenic gene expression and the protein secretion of hDPCs cultured with consecutive concentrations of MTA extracts and carefully examine the particular molecular mechanism that occurs during this process. METHODS: MTA extracts were prepared by immersing MTA powders into Dulbecco modified Eagle medium at a concentration of 200 mg/mL. hDPCs were cultured with various concentrations of MTA extracts, and the resulting changes in the cells, such as proliferation and odontogenic differentiation, were measured. RESULTS: The results indicate that hDPC proliferation increases remarkably in a time-dependent manner in most treatment groups, except the highest concentration group (200 mg/mL). The Wnt/beta-catenin signaling pathway-related genes and proteins are significantly raised when hDPCs are cultured in a wide concentration range of MTA extracts compared with a control, except for the highest concentration group (100 mg/mL), on days 3 and 7 (P < .05). CONCLUSIONS: These variations indicate that Wnt/beta-catenin signaling is involved in MTA extract-induced odontogenic differentiation of hDPCs. PMID- 27263049 TI - Protein engineering of Saccharomyces cerevisiae transporter Pdr5p identifies key residues that impact Fusarium mycotoxin export and resistance to inhibition. AB - Cereal infection by the broad host range fungal pathogen Fusarium graminearum is a significant global agricultural and food safety issue due to the deposition of mycotoxins within infected grains. Methods to study the intracellular effects of mycotoxins often use the baker's yeast model system (Saccharomyces cerevisiae); however, this organism has an efficient drug export network known as the pleiotropic drug resistance (PDR) network, which consists of a family of multidrug exporters. This study describes the first study that has evaluated the potential involvement of all known or putative ATP-binding cassette (ABC) transporters from the PDR network in exporting the F. graminearum trichothecene mycotoxins deoxynivalenol (DON) and 15-acetyl-deoxynivalenol (15A-DON) from living yeast cells. We found that Pdr5p appears to be the only transporter from the PDR network capable of exporting these mycotoxins. We engineered mutants of Pdr5p at two sites previously identified as important in determining substrate specificity and inhibitor susceptibility. These results indicate that it is possible to alter inhibitor insensitivity while maintaining the ability of Pdr5p to export the mycotoxins DON and 15A-DON, which may enable the development of resistance strategies to generate more Fusarium-tolerant crop plants. PMID- 27263050 TI - Defining chronic pancreatitis with a focus on pathological stress responses. PMID- 27263051 TI - GnIH plays a negative role in regulating GtH expression in the common carp, Cyprinus carpio L. AB - In birds and mammals, the gonadotrophin-inhibitory hormone (GnIH) effectively inhibits the expression of gonadotrophin (GtH). In teleosts, the effects of GnIH are still unclear and under much debate. The aim of this study is to evaluate the functions of GnIH/receptors of gonadotrophin-inhibitory hormone (GnIHRs) system during reproduction in the common carp, Cyprinus carpio L. We cloned the full cDNA sequences of GnIH /GnIHRs. Real-time PCR results showed that GnIH/GnIHRs were distributed extensively across the whole hypothalamus-pituitary-gonad (HPG) axis. We also examined the changes of GnIH/GnIHRs in the HPG axis during reproduction. GnIH mRNA expression was decreased to the minimum value in Apr, the spawning month, and increased immediately after the completion of reproduction. Expression pattern of GnIH during reproduction was the opposite to those of Gonadotrophin release hormone 3 (GnRH3) and luteinizing hormone (LH). Expression patterns of GnIHRs were similar to that of GnIH in the hypothalamus. In the pituitary, GnIHR2/3 peaked in March before spawning. In the ovaries, the GnIHR1 decreased to the minimum value in April, but GnIHR2/3 increased. By injection and incubation with synthesized GnIH-III peptide, we confirmed the negative influence of GnIH on mRNAs of the follicle-stimulating hormone-beta and LH-beta subunits in the common carp. These results show that the GnIH/GnIHRs system is involved in the negative regulation of reproduction in HPG axis of the common carp. PMID- 27263052 TI - Biogenesis and Function of Transfer RNA-Related Fragments (tRFs). AB - Noncoding small RNAs arise from the various un-annotated and annotated regions of the genome. When they arise from annotated genes, the noncoding small RNAs are functionally different from the parent genes. This is a brief review of one class of noncoding small RNAs, tRNA-related fragments (tRFs), which are generated from tRNA. tRFs have been suggested to have roles in cell proliferation, priming of viral reverse transcriptases, regulation of gene expression, RNA processing, modulation of the DNA damage response, tumor suppression, and neurodegeneration. PMID- 27263054 TI - Raising the Legal Age of Tobacco Sales: Policy Support and Trust in Government, 2014-2015, U.S. AB - INTRODUCTION: The National Academy of Medicine has called for an increase in the minimum age of tobacco product sales. It is not clear what age increase would garner the greatest public support, or whether trust in the U.S. government predicts policy support. METHODS: The data for these analyses are from a nationally representative telephone sample of U.S. adults (N=4,880) conducted from September 2014 to May 2015. The authors assessed whether support varied by the proposed minimum age of tobacco sales using a survey experiment (i.e., random assignment to the 19-, 20-, or 21-year age minimum condition) and, in cross sectional analyses, whether smoking status, individual demographics, state-level politics, and general trust in the government predicted policy support. Analyses were conducted from May to December 2015. RESULTS: Odds of support for raising the minimum sales age to 21 years trended higher than support for raising to age 20 or 19 years (AOR=1.22, 95% CI=0.97, 1.53, p=0.09). There was majority support for raising the age of sales for cigarettes in all regions of the U.S. (66.3%, 95% CI=64.0, 68.6). Race, age, and trust in government were significant predictors of support. CONCLUSIONS: Raising the age of tobacco sales is broadly supported by the public. An age 21 years tobacco sales policy trends toward garnering more support than a policy at age 19 or 20 years. Trust in government may be an important consideration in understanding policy support beyond demographics. PMID- 27263053 TI - The molecular characterization of Beta globin gene in thalassemia patients reveals rare and a novel mutations in Pakistani population. AB - INTRODUCTION: A multicentre study (including four cities in Pakistan) aimed to investigate the frequency and spectrum of alpha and beta thalassemia genetic mutations and XmnI polymorphism of the Gamma Globin gene. METHODS: One hundred and sixty one beta thalassemia patients, identified on the ground of haematological parameters, were screened for mutations of the Alpha (HBA2 and HBA1) and Beta (HBB) Globin genes as well as Gamma (HBG2) Globin gene, -158 Ggamma XmnI polymorphism, using a combination of multiplex GAP polymerase chain reaction (PCR), Sanger sequencing and restriction fragment length polymerase (RFLP) based PCR. RESULTS: Mutations of at least one HBB gene was identified in 157 of 161 patients screened. Among 16 identified mutations in the beta gene, HBB:c.27_28insG (p. Ser10Valfs*14) was the most prevalent. alpha(-3.7) and alpha( 4.2) deletions were co-inherited with beta thalassemia mutations. Rare mutations such as HBB:c.-138C > T and HBB:c.315 + 1G > A were also identified. One novel variant (HBB:c.-148T > A), two rare mutations [HBB:c.332T > C (p.Leu111Pro); HBB:c.92G > C (p.Arg31Thr] and a novel association, HBB:c.[92G > C (p.Arg31Thr)] and [-92C > G], were reported for the first time in our study. HBG2:c.-211C > T base-pair substitution (historically described as -158 GgammaXmnI polymorphism) was present in 36% of the patients. CONCLUSION: Heterogeneity in clinical and haematological parameters in TM, show that monogenic disorders can present with a wide spectrum of disease severity. Our studies identified rare and novel mutations that will be useful in the prevention of highly prevalent disease of thalassemia in Pakistan following nationwide awareness campaign. PMID- 27263055 TI - Comparison of the prognostic influence of emergency hepatectomy and staged hepatectomy in patients with ruptured hepatocellular carcinoma. AB - BACKGROUND: Spontaneous hepatocellular carcinoma (HCC) rupture is a fatal complication of primary liver cancer and is associated with poor surgical outcomes. Whether emergency hepatectomy or staged hepatectomy should be performed in the situations of a spontaneous rupture for resectable HCC need to be investigated. METHODS: Between January 2005 and December 2014, 131 patients with HCC ruptures received emergency or staged hepatectomy in our hospital and were included in this study. We retrospectively compared the postoperative morbidity and mortality, overall survival (OS), and disease-free survival (DFS) of patients who received emergency or staged hepatectomies. Independent prognostic predictors were identified using the Cox multivariate regression analysis. RESULTS: Emergency hepatectomy could be performed for successful surgical hemostasis and radical tumor resection. However, the in-hospital mortality rate was 11.0%, which correlated with INR, liver function, shock, blood transfusion, and aggressive treatment by emergency hepatectomy (P<0.05). Conversely, the 1-, 3-, and 5-year overall survival rates of ruptured HCC patients with staged hepatectomy were 82.8%, 55.2%, and 41.4%; and the disease-free survival rates were 70.7%, 44.8%, and 27.6%, respectively. The overall survival and disease-free survival of staged hepatectomy group were longer than that of emergency hepatectomy group (P=0.034, P=0.019). Multivariable analyses of HCC ruptures patients indicated that tumor sizes more than 10cm and multiple-nodule tumors were independent predictors of poor long-term survival. CONCLUSIONS: Though they carry some risk, emergency hepatectomy is still an important means of treatment for spontaneous HCC ruptures. For resectable HCC ruptures, emergency hepatectomy or staged hepatectomy are life-saving procedures, and efficient therapeutic methods. After the initial hemostasis, staged liver resection can often help patients achieve better long-term survival than emergency hepatectomy. PMID- 27263056 TI - Cost-effectiveness of doxorubicin-eluting beads versus conventional trans arterial chemo-embolization for hepatocellular carcinoma. AB - BACKGROUND: Doxorubicin-loaded drug-eluting beads TACE (DEB-TACE) has been developed to maximize the therapeutic efficacy of conventional trans-catheter arterial chemo-embolization (cTACE) in patients with hepatocellular carcinoma (HCC); however, its cost-effectiveness (CE) still needs to be assessed. AIMS: To investigate the CE of DEB-TACE versus cTACE. METHODS: Results from a meta analysis of the pertinent literature were used to construct a CE Markov simulation model which followed a hypothetical cohort of HCC patients who underwent DEB-TACE or cTACE, covering the entire post-TACE lifespan until death. Costs were assessed from the health-care provider perspective. RESULTS: Five randomized controlled trials (RCTs) and 11 observational studies, including 1860 patients (883 DEB-TACE and 977 cTACE), were used for the construction of the model. Considering only survival rates from RCTs (heterogeneity: 0%), DEB-TACE returned 4.0 quality-adjusted life-years (QALYs) and TACE returned 3.3 QALYs (effect size=1.288). Total costs of cTACE were ?10,389 and those of DEB-TACE were ?11,418 (effect size=0.791). DEB-TACE was found more cost-effective than cTACE when a minimum willingness-to-pay of about ?2000-3500/QALY was accepted, mainly depending on shorter in-hospital stay and better quality of life. CONCLUSIONS: Direct incremental costs of DEB-TACE can be acceptable in respect to cTACE, relying on financial resources available from the payer perspective. PMID- 27263057 TI - Anatomic structure-based deformable image registration of brachytherapy implants in the treatment of locally advanced cervix cancer. AB - PURPOSE: To examine the impact of anatomic structure-based image sets in deformable image registration (DIR) for cervical cancer patients. METHODS AND MATERIALS: CT examinations of 7 patients previously treated for locally advanced cervical cancer with external beam radiation therapy and from three to five fractions of high-dose-rate brachytherapy (HDR-BT) were used. Structure-based image sets were created from "free" structures already made for planning purposes, with each structure of interest assigned a unique, homogeneous Hounsfield number. Subsequent HDR fractions were registered to the pretreatment external beam radiation therapy and/or the first HDR fraction using commercially available software by rigid alignment (RIG) followed by DIR. Comparison methods included quantification of external contour displacement between source and target images and calculation of mean voxel displacement values. Registration results for structure-based image sets were then compared and contrasted to intensity-based registrations of the original grayscale images. RESULTS: Utilization of anatomic structure-based image sets resulted in better initial rigid matching (A-RIG) with more importance on applicator positioning and soft tissue structures. Subsequent DIR of anatomic structure-based images allowed for intermodality registrations, whereas all intermodality registrations using original CT images failed to produce anatomically feasible results. CONCLUSIONS: We have investigated the use of structure-based CT image sets for image registrations and have produced anatomically favorable registrations with excellent matching of external contours as compared to registrations of original grayscale images. Commercial software registrations using treatment-planning structures required no manual tweaking on a per-patient basis, suggesting results are reproducible and broadly applicable. PMID- 27263058 TI - Prospective analysis of toxicity in patients treated with strut-adjusted volume implant for early-stage breast cancer. AB - PURPOSE: We report the toxicity of patients treated with strut-adjusted volume implant (SAVI) for accelerated partial breast irradiation treated at our institution. METHODS AND MATERIALS: Patients treated from January 2013 to July 2015 with SAVI planned for 10 b.i.d. fractions for a total dose of 34 Gy were included. Acute and late toxicities were prospectively collected on patients in followup and graded by the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: A total of 132 patients were included, with 1 patient having synchronous breast cancer treated in each breast. Median followup was 20.0 months (range, 2.7-37.4 months). The median age at diagnosis was 61 years (range, 41-83 years). Forty-two lesions (32%) were in situ, 88 lesions (66%) were Stage 1, and 3 (2%) lesions were Stage 2. The median planning target volume was 58.2 cc (range, 24.2-109.9 cc), median V150 was 26.3 cc (range, 11.5-47.5 cc), and median V200 was 13.0 cc (range, 6.3-26.1 cc). On a pain scale of 0-10 (10 = worst pain), pain was worst on Day 2 of treatment, with an average score of 0.46. There was one acute skin infection; there were three late skin infections, two of which was Grade 3. Other late toxicities were Grade 1 or 2: hyperpigmentation (44%), telangiectasia (0.8%), seroma (9%), fat necrosis (5%), and fibrosis (12%). Crude local recurrence rate was 4%. CONCLUSION: SAVI is a safe treatment option for patients who are candidates for accelerated partial breast irradiation. Local control seems to be excellent, but longer followup is needed. PMID- 27263059 TI - Impact of source position on high-dose-rate skin surface applicator dosimetry. AB - PURPOSE: Skin surface dosimetric discrepancies between measured and treatment planning system predicted values were traced to source position sag inside the applicator and to source transit time. We quantified their dosimetric impact and propose corrections for clinical use. METHODS AND MATERIALS: We measured the dose profiles from the Varian Leipzig-style high-dose-rate (HDR) skin applicator, using EBT3 film, photon diode, and optically stimulated luminescence dosimeter for three different GammaMedplus HDR afterloaders. The measured dose profiles at several depths were compared with BrachyVision Acuros calculated profiles. To assess the impact of the source sag, two different applicator orientations were considered. The dose contribution during source transit was assessed by comparing diode measurements using an HDR timer and an electrometer timer. RESULTS: Depth doses measured using the three dosimeters were in good agreement, but were consistently higher than the Acuros dose calculations. Measurements with the applicator face up were significantly (exceeding 10%) lower than those in the face down position, due to source sag inside the applicator. Based on the inverse square law, the effective source sag was evaluated to be about 0.5 mm from the planned position. The additional dose during source transit was evaluated to be about 2.8% for 30 seconds of treatment with a 40700 U (10 Ci) source. CONCLUSION: With a very short source-to-surface distance, the small source sag inside the applicator has a significant dosimetric impact. This effect is unaccounted for in the vendor's treatment planning template and should be considered before the clinical use of the applicator. Further investigation of other applicators with large source lumen diameter may be warranted. PMID- 27263060 TI - Robustness to source displacement in dual air kerma strength planning for focal low-dose-rate brachytherapy of prostate cancer. AB - PURPOSE: To describe the use of dual source strength implants for focal low-dose rate brachytherapy. METHODS AND MATERIALS: An interneedle dual source strength planning strategy is described for focal low-dose-rate brachytherapy of the prostate. The implanted treatment plans were designed using peripheral (except near the rectum) needles loaded with high strength (0.9 U) sources and central needles loaded with low strength (0.4 U) sources ("interneedle" dual strength planning). This approach has been applied for focally treating 3 patients. In this article, we compare the characteristics and robustness to source motion of interneedle dual strength planning with four alternative planning strategies (single strength high, low, and intermediate, and intraneedle dual strength) on 50 simulated cases. RESULTS: Interneedle dual source strength planning results in greater robustness to source motion and overall lower seed and needle density compared to the standard low source strength planning currently used in our centre. This planning approach is also significantly superior to single strength high, single strength intermediate and intraneedle dual strength planning strategies in terms of high dose to the urethral avoidance structure. CONCLUSIONS: The use of interneedle dual source strength treatment plans for focal low-dose-rate brachytherapy is possibly the practical solution for limiting the density of sources required to deliver the prescribed dose while limiting proximity of high strength sources to organs at risk. PMID- 27263061 TI - Cesarean section and the manipulation of exact delivery time. AB - Physicians are often alleged responsible for the manipulation of delivery timing. We investigate this issue in a setting that negates the influence of financial incentives on physician's behavior. Working on a sample of women admitted at the onset of labor in a big public hospital in Italy we estimate a model for the exact time of delivery as driven by individual Indication to Cesarean Section (ICS) and covariates. We find that ICS does not affect the day of delivery but leads to a circadian rhythm in the likelihood of delivery. The pattern is consistent with the postponement of high ICS deliveries in the late night?early morning shift. Our evidence hardly supports the manipulation of timing of births as driven by medical staff's "demand for leisure". Physicians seem to manipulate the exact timing of delivery to reduce exposure to risk factors extant during off peak periods. PMID- 27263062 TI - Long term impact of the economic crisis on health care in the Greek setting: The Pandora box? PMID- 27263063 TI - Effects of the financial crisis and Troika austerity measures on health and health care access in Portugal. AB - Although Portugal has been deeply affected by the global financial crisis, the impact of the recession and subsequent austerity on health and to health care has attracted relatively little attention. We used several sources of data including the European Union Statistics for Income and Living Conditions (EU-SILC) which tracks unmet medical need during the recession and before and after the Troika's austerity package. Our results show that the odds of respondents reporting having an unmet medical need more than doubled between 2010 and 2012 (OR=2.41, 95% CI 2.01-2.89), with the greatest impact on those in employment, followed by the unemployed, retired, and other economically inactive groups. The reasons for not seeking care involved a combination of factors, with a 68% higher odds of citing financial barriers (OR=1.68, 95% CI 1.32-2.12), more than twice the odds of citing waiting times and inability to take time off work or family responsibilities (OR 2.18, 95% CI 1.20-3.98), and a large increase of reporting delaying care in the hope that the problem would resolve on its own (OR=13.98, 95% CI 6.51-30.02). Individual-level studies from Portugal also suggest that co payments at primary and hospital level are having a negative effect on the most vulnerable living in disadvantaged areas, and that health care professionals have concerns about the impact of recession and subsequent austerity measures on the quality of care provided. The Portuguese government no longer needs external assistance, but these findings suggest that measures are now needed to mitigate the damage incurred by the crisis and austerity. PMID- 27263064 TI - Prognostic impact of comorbidities in hospitalized patients with acute exacerbation of chronic heart failure. AB - BACKGROUND: To assess the impact of comorbidities on long-term all-cause mortality in patients hospitalized with exacerbated signs/symptoms of previously chronic stable HF (AE-CHF). METHODS: 1119 patients admitted for AE-CHF and with NT-proBNP levels >900pg/mL were enrolled. Univariable and multivariable Cox analyses were performed to assess the association of age, gender, hypertension, diabetes, obesity, atrial fibrillation, coronary heart disease (CHD), chronic obstructive pulmonary disease, previous cerebrovascular accidents, chronic liver disease (CLD), thyroid disease, renal impairment (RI), and anemia with 3-year all cause mortality. RESULTS: During the follow-up, 441 patients died and 126 underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. 45.8% of the fatal events and 52.4% of HT/VAD implantations occurred within 180days after admission. Increasing age (p=.012), obesity (p=.037), atrial fibrillation (p=.030), CHD (p=.015), CLD (p=.001), RI (p<.001), and anemia (p<.001) were independently associated with 3-year all-cause mortality. Most of the prognostic impact of CHD, took place within the first 180days after admission. Male gender was associated with mortality beyond 180days. Compared with normal weight, obesity was associated with better overall survival. Obese patients, however, had significantly lower NT-proBNP concentrations and less frequently presented with hypotension, hyponatremia, and severe left ventricular systolic dysfunction, despite a similar prevalence of severe dyspnea at admission. CONCLUSIONS: Several comorbidities are associated with long-term risk of death in hospitalized patients with worsening HF, although the nature of this association does appear to be complex. Our data may help to raise awareness about the clinical relevance of comorbid conditions. PMID- 27263065 TI - Mathematical modeling to predict the sub-bandage pressure on a conical limb for multi-layer bandaging. AB - The effectiveness of the compression treatment by a medical compression bandage is dependent on the pressure generated at the interface between the bandage and the skin. This pressure is called interface pressure or sub-bandage pressure. The performance of a bandage depends upon the level of interface pressure applied by the bandage and the sustenance of this pressure over time. The interface pressure exerted by the bandage depends on several other factors like limb shape or size, application technique, physical and structural properties of the bandage, physical activities taken by the patient, etc. The current understanding of how bandages apply pressure to a limb is based on the Law of Laplace, which states that tension in the walls of a container is dependent on both the pressure of the container's content and its radius. This concept was translated mathematically into equation relating pressure to tension and radius by Thomas. In addition, a modified equation was generated by multiplying the model with a constant that represents the number of bandage layers in order to use the model to estimate the pressure applied by multi-layer bandages. This simple multiplication adjustment was questioned by researchers. They had doubts about the model validity and whether it can be used to predict the sub-bandage pressure applied by pressure garments. One of the questions that were raised regarding the bandage thickness affecting the sub-bandage pressure has been recently explored by Al Khaburi where he used the thin and thick cylinder shell theory to study the effect of Multi Component Bandage's (MCB) thickness on the sub-bandage pressure. The model by Al Khaburi and the earlier models developed for pressure prediction are all based on calculations considering the cylindrical limb shapes although the human limb normally is wider at the calf and reduces in circumference towards the ankle. So in our approach, the bandage is assumed to take a conical shape during application and membrane shell theory is used for developing pressure prediction model for multi-layers of bandage. Both analytical and experimental work showed that the effect of bandage thickness and the geometry of the limb on pressure produced by multi-layers of bandage are significant. The model developed when compared to the data obtained using experimental setup confirmed the validity of the mathematical model for multi-layers of bandage based on conical geometry of the limb. PMID- 27263066 TI - Corrigendum to "The contact mechanics and occurrence of edge loading in modular metal-on-polyethylene total hip replacement during daily activities." [Medical Engineering & Physics, Volume 38, Issue 6 (June 2016) Pages 518-525]. PMID- 27263067 TI - [Lumbar spinal angiolipoma]. AB - Spinal angiolipomas are fairly infrequent benign tumours that are usually located in the epidural space of the thoracic column and represent 0.14% to 1.3% of all spinal tumours. Lumbar angiolipomas are extremely rare, representing only 9.6% of all spinal extradural angiolipomas. We report the case of a woman who complained of a lumbar pain of several months duration with no neurological focality and that had intensified in the last three days without her having had any injury or made a physical effort. The MR revealed an extradural mass L1-L2, on the posterior face of the medulla, decreasing the anteroposterior diameter of the canal. The patient symptoms improved after surgery. Total extirpation of the lesion is possible in most cases, and the prognosis is excellent even if the lesion is infiltrative. For this reason, excessively aggressive surgery is not necessary to obtain complete resection. PMID- 27263068 TI - Impact of short-term refeeding on appetite and meal experiences in new onset adolescent eating disorders. AB - Restrictive eating disorders (ED) are increasing and represent a serious risk to the health of adolescent females. Restrictive ED in youth are often treated through aggressive short-term refeeding. Although evidence supports that this intervention is the "gold standard" for improving ED outcomes in youth, little research has specifically probed appetite and meal-related responses to this type of intensive, short-term refeeding in newly diagnosed individuals. Information about appetite and meal-related dysfunction could provide valuable insights regarding treatment-interfering features of ED in both acute inpatient and longer term outpatient treatment. The purpose of this study was to evaluate the hunger, fullness, olfactory, and gustatory responses of adolescents with newly-diagnosed restrictive ED and to probe how and when these responses are altered by refeeding. Using a quasi-experimental ecologically valid methodology, this study described and compared profiles of hunger, fullness, olfactory, and gustatory responses in adolescent females (n = 15) with newly diagnosed restrictive ED at hospital admission (i.e., severe malnutrition) and after medical refeeding, in comparison to healthy controls (n = 15). Results showed that newly diagnosed (i.e., malnourished) adolescents with ED showed significantly different meal related experiences than controls. Refeeding improved some of these differences, but not all. Following refeeding, females with ED continued to show lower hunger, greater fullness, and lower pleasantness of smell ratings compared to controls. Unpleasantness of taste ratings maladaptively increased, such that females who were re-fed reported more aversive scents than pre-treatment. Profiles of meal related responses were also identified and compared between groups. The applicability of these findings are discussed within the context of critical periods of change during refeeding treatment and potentially promising intervention targets that might enhance treatment outcomes for adolescents with newly onset, restrictive ED. PMID- 27263069 TI - Childhood risk factors for lifetime bulimic or compulsive eating by age 30 years in a British national birth cohort. AB - OBJECTIVE: To examine whether previously identified childhood risk factors for bulimia or compulsive eating (BCE) predict self-reported lifetime BCE by age 30 years in a prospective birth cohort. METHOD: Using data from the 1970 British Cohort Study at birth, 5, and 10 years, associations between 22 putative childhood risk factors and self-reported lifetime BCE at 30 years were examined, adjusting for sex and socioeconomic status. RESULTS: Only female sex (odds ratio (OR): 9.2; 95% confidence interval (CI): 1.9-43.7; p = 0.005), low self-esteem (OR:2.9; 95%CI: 1.1-7.5; p = 0.03) and high maternal education (OR:5.4; 95%CI: 2.0-14.8; p = 0.001) were significantly associated with higher risk of BCE, whereas high SES at 10 years was significantly protective (OR:0.2; 95%CI: 0.1 0.8; p = 0.022) of BCE in fully adjusted multivariable logistic regression analysis. DISCUSSION: Our findings do not support a strong role for childhood weight status and eating behaviours in the development of bulimia and compulsive eating pathology, rather suggesting a focus on self esteem may have greater relative importance. Findings in relation to maternal education and SES need further exploration. PMID- 27263070 TI - Investigating the role of parent and child characteristics in healthy eating intervention outcomes. AB - While numerous studies have investigated the efficacy of interventions at increasing children's vegetable consumption, little research has examined the effect of individual characteristics on intervention outcomes. In previous research, interventions consisting of modelling and rewards have been shown to increase children's vegetable intake, but differences were identified in terms of how much children respond to such interventions. With this in mind, the current study investigated the role of parental feeding practices, child temperament, and child eating behaviours as predictors of intervention success. Parents (N = 90) of children aged 2-4 years were recruited from toddler groups across Leicestershire, UK. Parents completed measures of feeding practices, child eating behaviours and child temperament, before participating in one of four conditions of a home-based, parent led 14 day intervention aimed at increasing their child's consumption of a disliked vegetable. Correlations and logistic regressions were performed to investigate the role of these factors in predicting intervention success. Parental feeding practices were not significantly associated with intervention success. However, child sociability and food fussiness significantly predicted intervention success, producing a regression model which could predict intervention success in 61% of cases. These findings suggest that future interventions could benefit from being tailored according to child temperament. Furthermore, interventions for children high in food fussiness may be better targeted at reducing fussiness in addition to increasing vegetable consumption. PMID- 27263071 TI - Complete zona pellucida removal from vitrified-warmed human blastocysts facilitates earlier in-vitro attachment and outgrowth. AB - Partial removal of the zona pellucida (ZP) has been performed using a laser system to promote hatching of vitrified-warmed blastocysts. However, low viability blastocysts cannot hatch even after partial ZP removal. This study examined whether complete removal of the ZP improves embryonic adhesion and outgrowth of vitrified-warmed blastocysts compared with partial removal, using a blastocyst outgrowth model. In all, 217 vitrified human blastocysts, which were discarded and donated for research by consenting couples, were warmed and subjected to assisted hatching to remove the ZP partially or completely, or did not undergo assisted hatching (zona intact controls). Blastocysts were cultured using time-lapse microscopy to monitor hatching, adhesion and outgrowth. Despite partial ZP removal, 36% of blastocysts failed to hatch. Blastocyst outgrowth assays showed improved adhesion rate, shorter time for adhesion and larger outgrowth area in the blastocysts with completely removed ZP compared with those with partially-removed ZP. mRNA expression of integrin alpha5 and beta1 was upregulated in blastocysts with completely removed ZP compared with those with partially-removed ZP. Study findings reveal the advantages of complete ZP removal for assisted hatching. In conclusion, complete ZP removal increases the chance of blastocyst adhesion and subsequent outgrowth in vitro after the vitrification warming procedure. PMID- 27263072 TI - Different reserve proxies confer overlapping and unique endurance to cortical thinning in healthy middle-aged adults. AB - AIM: To investigate different proxies of brain and cognitive reserve as potential mediators of the effect of cortical thinning on cognition in healthy middle-aged adults. METHODS: Eighty-two middle-aged individuals were included (mean(SD) age=45.1(3.9)years). Cortical thickness was calculated for multiple brain regions using FreeSurfer. Cognitive measures sensitive to early cognitive decline were selected, including Block Design from the Wechsler Adult Intelligence Scale-III (WAIS-III), Judgment of Line Orientation Test (JLOT), Color Trails Test (CTT), and first learning trial of TAVEC (the Spanish version of the California Verbal Learning Test, CVLT). Brain reserve was operationalized as total intracranial volume (TIV); and cognitive reserve was estimated by means of Years of Education, WAIS-III Vocabulary subtest, WAIS-III Information subtest, and a Cognitive Reserve Questionnaire (CRQ). Mediation effects were investigated with multiple linear regression and bootstrapping analysis. RESULTS: Information and Vocabulary showed the greatest mediation capacity. All the observed mediations were positive indicating that higher levels of reserve attenuate the effect of reduced cortical thickness on cognition. Information, Vocabulary and TIV buffered the effect of frontal thinning on Block Design; Vocabulary and Years of Education buffered the effect of frontal thinning on JLOT; and CRQ buffered the effect of temporal thinning on CTT. CONCLUSION: Higher reserve buffers the effect of cortical thinning on cognition in healthy middle-aged adults. The investigated proxies might be underpinned by slightly different neural networks. Advancing in the understanding of the influences of reserve in healthy middle-aged adults is crucial to facilitate early interventions. PMID- 27263073 TI - Fluoxetine normalizes the effects of prenatal maternal stress on depression- and anxiety-like behaviors in mouse dams and male offspring. AB - Maternal depression during pregnancy and the postpartum period (lactation) is a common debilitating condition affecting mother-fetus/-infant interactions, which can be a risk factor for cognitive and affective disorders in mothers and their children. Selective-serotonin-reuptake-inhibitor-(SSRI) pharmacotherapy is known as the first-line treatment of maternal depression. However, its use during pregnancy and lactation is a topic of concern. The present study aimed to investigate the effects of prenatal stress alone or in combination with fluoxetine (FLX) on hypothalamic-pituitary-adrenal axis (HPA) activity, anxiety /depression-like behaviors in dams and in offspring. To do this, gestationally stressed and non-stressed mouse dams were orally treated with FLX-(8/mg/kg/day) from gestational day 10 to lactation day 20. The behavioral outcomes of prenatal stress and FLX treatment in dams and male offspring were assessed using the sucrose preference, forced swim, zero maze, and light-dark box tests. Stress induced corticosterone levels were also evaluated as indicative of abnormal HPA axis function. Our findings indicated that maternal stress resulted in increased depression-like behavior and HPA axis hyperactivity in dams during pregnancy and lactation which were reversed by FLX. Furthermore, prenatal stress increased anxiety/depression-like behaviors and HPA-axis reactivity in male offspring. These effects were reversed by maternal FLX treatment. Developmental FLX exposure, without prenatal stress, did not have any adverse effects on the above measured parameters. Our results suggest that prenatal stress induces maternal depression-like behavior which affects the development of affective symptoms in male offspring, and that remediation of maternal depression-like behavior coincidences with the normalization of anxiety-and depression-like symptoms in male offspring. PMID- 27263075 TI - Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome - A challenging diagnosis not to be missed. AB - SAPHO syndrome manifests as chronic inflammation of bones and joints, which may or may not be accompanied by skin changes. The term SAPHO is an acronym that stands for synovitis, acne, pustulosis (usually palmoplantar), hyperostosis and osteitis. The bones most commonly affected are those in the anterior chest wall (mainly the sternum, clavicles and sternocostoclavicular joints), the vertebrae and the sacroiliac joints, but peripheral and flat bones may also be involved, especially in children. There are no validated diagnostic criteria for SAPHO, and diagnosis is based on clinical and radiological findings. One of the main challenges in diagnosis is that the clinical features may occur many years apart. Additionally, patients may not develop all manifestations. Delayed diagnosis, as a result of a lack of awareness of SAPHO, can lead to patients suffering ongoing pain and disfiguring skin manifestations. One theory is that Propionibacterium acnes (isolated from bone biopsies in many SAPHO patients) triggers an auto immune mediated chronic inflammation in genetically predisposed individuals. Treatment involves the use of nonsteroidal anti-inflammatory drugs, intra articular steroids, bisphosphonates and biologicals. The course of SAPHO is often prolonged but, despite the challenges in diagnosis and treatment, the long-term prognosis is good. PMID- 27263076 TI - Optimizing antimicrobial therapy in children. AB - Management of common infections and optimal use of antimicrobial agents are presented, highlighting new evidence from the medical literature that enlightens practice. Primary therapy of staphylococcal skin abscesses is drainage. Patients who have a large abscess (>5 cm), cellulitis or mixed abscess-cellulitis likely would benefit from additional antibiotic therapy. When choosing an antibiotic for outpatient management, the patient, pathogen and in vitro drug susceptibility as well as tolerability, bioavailability and safety characteristics of antibiotics should be considered. Management of recurrent staphylococcal skin and soft tissue infections is vexing. Focus is best placed on reducing density of the organism on the patient's skin and in the environment, and optimizing a healthy skin barrier. With attention to adherence and optimal dosing, acute uncomplicated osteomyelitis can be managed with early transition from parenteral to oral therapy and with a 3 4 week total course of therapy. Doxycycline should be prescribed when indicated for a child of any age. Its use is not associated with dental staining. Azithromycin should be prescribed for infants when indicated, whilst being alert to an associated >=2-fold excess risk of pyloric stenosis with use under 6 weeks of age. Beyond the neonatal period, acyclovir is more safely dosed by body surface area (not to exceed 500 mg/m(2)/dose) than by weight. In addition to the concern of antimicrobial resistance, unnecessary use of antibiotics should be avoided because of potential later metabolic effects, thought to be due to perturbation of the host's microbiome. PMID- 27263074 TI - The Family Communication Study: A randomized trial of prospective pediatric palliative care consultation, study methodology and perceptions of participation burden. AB - BACKGROUND: To describe the study methods, baseline characteristics and burden of study procedures of an intervention designed to reduce family stress symptoms through early support from the palliative care team. Length of stay of >=8days was the trigger for early palliative care involvement. METHODS: Cluster randomized trial with children as the unit of randomization. Up to 3 family members per child were recruited. Family stress symptoms were recorded at baseline, discharge from the ICU, and 3months post-enrollment. Questionnaire burden was assessed on a 1-10 point scale at each time point and open-ended comments were analyzed to describe the participants' experience in the study. RESULTS: 380 family members of 220 children (control=115 children and 204 family members; intervention=105 children and 176 family members) were recruited, which represented 50% of all eligible families. Most family participants were parents (86% control; 92% intervention) and female (66% both groups). Retention rates were high through the 3-month follow-up: 93% and 90% for the control and intervention groups respectively. Questionnaire burden was very low: mean (sd) scores were 1.1 (1.6), 0.7 (1.5), and 0.9 (1.6) for the baseline, discharge and follow-up questionnaires, respectively. Comments suggest that participation was beneficial by promoting reflection and self-awareness about stress, coping and resilience, and feeling cared for because the intervention and questionnaires focused on their own well-being. CONCLUSIONS: The participants' comments regarding the focus on them as the point of intervention reflects the value of conducting research with family members of seriously ill children during ICU stays. PMID- 27263077 TI - HDL mimetic CER-001 targets atherosclerotic plaques in patients. AB - BACKGROUND AND AIMS: Infusion of high-density lipoprotein (HDL) mimetics aimed at reducing atherosclerotic burden has led to equivocal results, which may relate in part to the inability of HDL mimetics to adequately reach atherosclerotic lesions in humans. This study evaluated delivery of recombinant human apolipoprotein A-I (apoA-I) containing HDL mimetic CER-001 in carotid plaques in patients. METHODS: CER-001 was radiolabeled with the long-lived positron emitter zirconium-89 ((89)Zr) to enable positron emission tomography with computed tomography (PET/CT) imaging. Eight patients with atherosclerotic carotid artery disease (>50% stenosis) received a single infusion of unlabeled CER-001 (3 mg/kg), co administered with 10 mg of (89)Zr-labeled CER-001 (18 MBq). Serial PET/CT imaging and contrast enhanced-magnetic resonance imaging (CE-MRI) were performed to evaluate targeted delivery of CER-001. RESULTS: One hour after infusion, mean plasma apoA-I levels increased by 9.9 mg/dL (p = 0.026), with a concomitant relative increase in the plasma cholesterol efflux capacity of 13.8% (p < 0.001). Using serial PET/CT imaging, we showed that arterial uptake of CER-001 expressed as target-to-background ratio (TBRmax) increased significantly 24 h after infusion, and remained increased up to 48 h (TBRmax t = 10 min: 0.98; t = 24 h: 1.14 (p = 0.001); t = 48 h: 1.12 (p = 0.007)). TBRmax was higher in plaque compared with non-plaque segments (1.18 vs. 1.05; p < 0.001). Plaque TBRmax correlated with local plaque contrast enhancement (r = 0.56; p = 0.019) as assessed by CE-MRI. CONCLUSIONS: Infusion of HDL mimetic CER-001 increases plasma apoA-I concentration and plasma cholesterol efflux capacity. Our data support the concept that CER-001 targets plaque regions in patients, which correlates with plaque contrast enhancement. These clinical findings may also guide future nanomedicine development using HDL particles for drug delivery in atherosclerosis. CLINICAL TRIAL REGISTRATION: Netherlands Trial Registry - NTR5178. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5178. PMID- 27263078 TI - High shear stress relates to intraplaque haemorrhage in asymptomatic carotid plaques. AB - BACKGROUND AND AIMS: Carotid artery plaques with vulnerable plaque components are related to a higher risk of cerebrovascular accidents. It is unknown which factors drive vulnerable plaque development. Shear stress, the frictional force of blood at the vessel wall, is known to influence plaque formation. We evaluated the association between shear stress and plaque components (intraplaque haemorrhage (IPH), lipid rich necrotic core (LRNC) and/or calcifications) in relatively small carotid artery plaques in asymptomatic persons. METHODS: Participants (n = 74) from the population-based Rotterdam Study, all with carotid atherosclerosis assessed on ultrasound, underwent carotid MRI. Multiple MRI sequences were used to evaluate the presence of IPH, LRNC and/or calcifications in plaques in the carotid arteries. Images were automatically segmented for lumen and outer wall to obtain a 3D reconstruction of the carotid bifurcation. These reconstructions were used to calculate minimum, mean and maximum shear stresses by applying computational fluid dynamics with subject-specific inflow conditions. Associations between shear stress measures and plaque composition were studied using generalized estimating equations analysis, adjusting for age, sex and carotid wall thickness. RESULTS: The study group consisted of 93 atherosclerotic carotid arteries of 74 participants. In plaques with higher maximum shear stresses, IPH was more often present (OR per unit increase in maximum shear stress (log transformed) = 12.14; p = 0.001). Higher maximum shear stress was also significantly associated with the presence of calcifications (OR = 4.28; p = 0.015). CONCLUSIONS: Higher maximum shear stress is associated with intraplaque haemorrhage and calcifications. PMID- 27263079 TI - Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy. AB - OBJECTIVE: The aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG). METHODS: According to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ-mesial MRI-negative TLE or neocortical SOZ-neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology. RESULTS: Thirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p=0.031) and more seizures without clear lateralization of ictal activity (p=0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found. CONCLUSIONS: According to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach. PMID- 27263080 TI - Analysis of driver injury severity in wrong-way driving crashes on controlled access highways. AB - For more than five decades, wrong-way driving (WWD) has been notorious as a traffic safety issue for controlled-access highways. Numerous studies and efforts have tried to identify factors that contribute to WWD occurrences at these sites in order to delineate between WWD and non-WWD crashes. However, none of the studies investigate the effect of various confounding variables on the injury severity being sustained by the at-fault drivers in a WWD crash. This study tries to fill this gap in the existing literature by considering possible variables and taking into account the ordinal nature of injury severity using three different ordered-response models: ordered logit or proportional odds (PO), generalized ordered logit (GOL), and partial proportional odds (PPO) model. The findings of this study reveal that a set of variables, including driver's age, condition (i.e., intoxication), seatbelt use, time of day, airbag deployment, type of setting, surface condition, lighting condition, and type of crash, has a significant effect on the severity of a WWD crash. Additionally, a comparison was made between the three proposed methods. The results corroborate that the PPO model outperforms the other two models in terms of modeling injury severity using our database. Based on the findings, several countermeasures at the engineering, education, and enforcement levels are recommended. PMID- 27263081 TI - Prolonged exposure to salt stress affects specialized metabolites-artemisinin and essential oil accumulation in Artemisia annua L.: metabolic acclimation in preferential favour of enhanced terpenoid accumulation accompanying vegetative to reproductive phase transition. AB - Artemisia annua accumulates substantial quantities of unique and highly useful antimalarial sesquiternoid artemisinin and related phytomolecules as well as its characteristic essential oil in its glandular trichomes. The phytomolecules are mainly produced in its leaves and inflorescences. Artemisia annua plants were grown under NaCl salinity (50, 100 and 200 mM) stress conditions imposed throughout the entire life cycle of the plant. Results revealed that specialized metabolites like artemisinin, arteannuin-B, artemisinic acid + dihydroartemisinic acid and essential oil accumulation were positively modulated by NaCl salinity stress. Interestingly, total content of monoterpenoids and sesquiterpenoids of essential oil was induced by NaCl salinity treatment, contrary to previous observations. Production of camphor, the major essential oil constituent was induced under the influence of treatment. The metabolic acclimation and manifestations specific to terpenoid pathway are analysed vis-a-vis vegetative to reproductive periods and control of the modulation. WRKY and CYP71AV1 play a key role in mediating the responses through metabolism in glandular trichomes. The distinctness of the salinity induced responses is discussed in light of differential mechanism of adaptation to abiotic stresses and their impact on terpenoid-specific metabolic adjustments in A. annua. Results provide potential indications of possible adaptation of A. annua under saline conditions for agrarian techno-economic benefaction. PMID- 27263082 TI - Abscisic acid-deficient sit tomato mutant responses to cadmium-induced stress. AB - There is a very effective cross-talk between signals triggered by reactive oxygen species and hormonal responses in plants, activating proteins/enzymes likely to be involved in stress tolerance. Abscisic acid (ABA) is known as a stress hormone that takes part in the integration of signals. This work aimed to characterize the biochemical response and ultrastructural changes induced by cadmium (Cd) in the Micro-Tom (MT) sitiens ABA-deficient mutant (sit) and its wild-type (MT) counterpart. MT and sit plants were grown over a 96-h period in the presence of Cd (0, 10, and 100 MUM CdCl2). The overall results indicated increases in lipid peroxidation, hydrogen peroxide content and in the activities of the key antioxidant enzymes such as catalase, glutathione reductase, and ascorbate peroxidase in both genotypes. On the other hand, no alteration was observed in chlorophyll content, while the activity of another antioxidant enzyme, superoxide dismutase, remained constant or even decreased in the presence of Cd. Roots and shoots of the sit mutant and MT were analyzed by light and transmission electron microscopy in order to characterize the structural changes caused by the exposure to this metal. Cd caused a decrease in intercellular spaces in shoots and a decrease in cell size in roots of both genotypes. In leaves, Cd affected organelle shape and internal organization of the thylakoid membranes, whereas noticeable increase in the number of mitochondria and vacuoles in MT and sit roots were observed. These results add new information that should help unravel the relative importance of ABA in regulating the cell responses to stressful conditions induced by Cd apart from providing the first characterization of this mutant to oxidative stress. PMID- 27263083 TI - Development of gravitropic response: unusual behavior of flax phloem G-fibers. AB - The major mechanism of gravitropism that is discussed for herbal plants is based on the nonuniform elongation of cells located on the opposite stem sides, occurring in the growing zone of an organ. However, gravitropic response of flax (Linum usitatissimum L.) is well-pronounced in the lower half of developing stem, which has ceased elongation long in advance of plant inclination. We have analyzed the stem curvature region by various approaches of microscopy and found the undescribed earlier significant modifications in primary phloem fibers that have constitutively developed G-layer. In fibers on the pulling stem side, cell portions were widened with formation of "bottlenecks" between them, leading to the "sausage-like" shape of a cell. Lumen diameter in fiber widening increased, while cell wall thickness decreased. Callose was deposited in proximity to bottlenecks and sometimes totally occluded their lumen. Structure of fiber cell wall changed considerably, with formation of breaks between G- and S-layers. Thick fibrillar structures that were revealed in fiber cell wall by light microscopy got oblique orientation instead of parallel to the fiber axis one in control plants. The described changes occurred at various combinations of gravitational and mechanical stimuli. Thus, phloem fibers with constitutively formed gelatinous cell wall, located in nonelongating parts of herbal plant, are involved in gravitropism and may become an important element in general understanding of the gravity effects on plants. We suggest flax phloem fibers as the model system to study the mechanism of plant position correction, including signal perception and transduction. PMID- 27263084 TI - Feasibility of robot-assisted modified radical neck dissection by post-auricular facelift approach. AB - The aim of this study was to evaluate the technical feasibility and safety of robot-assisted modified radical neck dissection (MRND) for head and neck cancer patients with a clinically node-positive neck. The cases of 10 head and neck cancer patients who underwent unilateral therapeutic robot-assisted MRND by post auricular facelift approach were analyzed. The robot-assisted MRND was completed successfully in all patients without any conversion to conventional neck dissection. The mean number of lymph nodes removed was 36.7+/-8.6. The mean duration of surgery for robot-assisted MRND was 274+/-65min (range 175-395min). Transient marginal nerve palsy occurred in two patients and partial necrosis of the skin flap occurred in one patient. In terms of cosmetic satisfaction, 70% of patients were very satisfied or satisfied with postoperative cosmesis. In conclusion, robot-assisted MRND by post-auricular facelift approach is technically feasible and safe in selected patients with head and neck cancer, and yields excellent postoperative cosmesis. PMID- 27263085 TI - Haptic feedback helps bipedal coordination. AB - The present study investigated whether special haptic or visual feedback would facilitate the coordination of in-phase, cyclical feet movements of different amplitudes. Seventeen healthy participants sat with their feet on sliding panels that were moved externally over the same or different amplitudes. The participants were asked to generate simultaneous knee flexion-extension movements, or to let their feet be dragged, resulting in reference foot displacements of 150 mm and experimental foot displacements of 150, 120, or 90 mm. Four types of feedback were given: (1) special haptic feedback, involving actively following the motions of the sliders manipulated by two confederates, (2) haptic feedback resulting from passive motion, (3) veridical visual feedback, and (4) enhanced visual feedback. Both with respect to amplitude assimilation effects, correlations and standard deviation of relative phase, the results showed that enhanced visual feedback did not facilitate bipedal independence, but haptic feedback with active movement did. Implications of the findings for movement rehabilitation contexts are discussed. PMID- 27263086 TI - Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber. AB - BACKGROUND: Immediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis. OBJECTIVE: To examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC). METHODS: Fifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m(3) for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored. RESULTS: The severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased. CONCLUSION: Various mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure. PMID- 27263087 TI - Coronary spasm secondary to biphasic anaphylaxis after hymenoptera stings. PMID- 27263088 TI - Hospitalized hunger-striking prisoners: the role of ethics consultations. AB - We refer to hospitalized convicted hunger strikers in Padua Hospital who decided to fast for specific reasons, often demanding, to be heard by the judge, to complain about the existing custodial situation or to claim unjust treatment. The medical ethics of hunger strikers are debated because the use of force feeding by physicians is widely condemned as unethical, but courts, in Italy, sometimes order to transfer the convicted person to hospital and oblige healthcare practitioners to perform forcible feeding. This can engender a profound insecurity for the physicians taking action on the one hand, while preventing patients from fully availing themselves of this principle of self-determination on the other. Physicians are mainly concerned about how to manage this situation and they may request ethical consultation. When it comes to managing hospitalized hunger strikers, the ethics consultant may be able to facilitate the relationship between physicians and hunger strikers, enhance the latter's trust in the former, ensuring that strikers are aware of the risks associated with their fasting, and helping them to arrive of their own free will at the right decision concerning their behavior and their demands. PMID- 27263089 TI - Organ donation after assisted death: Is it more or less ethically-problematic than donation after circulatory death? AB - A provocative question has emerged since the Supreme Court of Canada's decision on assisted dying: Should Canadians who request, and are granted, an assisted death be considered a legitimate source of transplantable organs? A related question is addressed in this paper: is controlled organ donation after assisted death (cDAD) more or less ethically-problematic than standard, controlled organ donation after circulatory determination of death (cDCDD)? Controversial, ethics related dimensions of cDCD that are of relevance to this research question are explored, and morally-relevant distinctions between cDAD and cDCD are identified. In addition, a set of morally-relevant advantages of one practice over the other is uncovered, and a few potential, theoretical issues specifically related to cDAD practice are articulated. Despite these concerns, the analysis suggests a counterintuitive conclusion: cDAD is, overall, less ethically-problematic than cDCDD. The former practice better respects the autonomy interests of the potential donor, and a claim regarding irreversibility of cessation of the donor's circulatory function in the cDAD context can be supported. Further, with cDAD, there is no possibility that the donor will have negative sensory experiences during organ procurement surgery. Although the development of appropriate policy-decision and regulatory approaches in this domain will be complex and challenging, the comparative ethical analysis of these two organ donation practices has the potential to constructively inform the deliberations of relevant stakeholders, resource persons and decision makers. PMID- 27263090 TI - Prenatal marijuana exposure impacts executive functioning into young adulthood: An fMRI study. AB - Understanding the potentially harmful long term consequences of prenatal marijuana exposure is important given the increase in number of pregnant women smoking marijuana to relieve morning sickness. Altered executive functioning is one area of research that has suggested negative consequences of prenatal marijuana exposure into adolescence. Investigating if these findings continue into young adulthood and exploring the neural basis of these effects was the purpose of this research. Thirty one young adults (ages 18-22years) from the longitudinal Ottawa Prenatal Prospective Study (OPPS) underwent functional magnetic resonance imaging (fMRI) during four tasks; 1) Visuospatial 2-Back, 2) Go/NoGo, 3) Letter 2-Back and 4) Counting Stroop task. Sixteen participants were prenatally exposed to marijuana while 15 had no prenatal marijuana exposure. Task performance was similar for both groups but blood flow was significantly different between the groups. This paper presents the results for all 4 tasks, highlighting the consistently increased left posterior brain activity in the prenatally exposed group compared with the control group. These alterations in neurophysiological functioning of young adults prenatally exposed to marijuana emphasizes the importance of education for women in child bearing years, as well as for policy makers and physicians interested in the welfare of both the pregnant women and their offspring's future success. PMID- 27263091 TI - Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles. AB - We investigated the associations among gestational factors including prenatal marijuana exposure (PME), child behavior at age 3, early age of onset of marijuana use (EAOM, <15years), and adult roles at 22years. Participants were drawn from the Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of prenatal substance exposure in offspring who have been studied for over 22years since the prenatal phase. Data from the prenatal, birth, 3-, and 22-year phases (N=608) were used in the present study. Age of onset of offspring substance use was determined based on data from the 14-, 16-, and 22 year phases. The subjects were of lower socioeconomic status, 43% were Caucasian and the remaining were African-American, and 48% were males. Early childhood behavior was significantly (p<0.05) related to EAOM after controlling for PME, birth and childhood environmental risk factors, and Conduct Disorder. EAOM was significantly associated with negative adult roles including increased risk of being arrested (p<0.001), lower educational attainment (p<0.001), having a child without being married (p<0.05), and unemployment at 22years (p<0.001). The correlations between PME and negative adult roles and between early childhood behavior and negative adult roles were also statistically significant. Pathway analysis demonstrated that EAOM significantly mediated the associations between PME and fulfillment of adult roles and between early childhood behavior and adult roles. There are a number of intervention points that could be targeted that would have a long-term impact on lowering the probability of EAOM and less success in adult roles. PMID- 27263092 TI - Diapause in ticks of the medically important Ixodes ricinus species complex. AB - Four members of the Ixodes ricinus species complex, Ixodes pacificus, Ixodes persulcatus, Ixodes ricinus and Ixodes scapularis, have, between them, a worldwide distribution within the northern hemisphere. They are responsible for the transmission of several animal and human pathogens, including the causal agents of Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis and human babesiosis. Despite the importance of these ticks as vectors, the knowledge and understanding of the role that diapause plays in their complex life cycles are confused and incomplete. In view of the continuing geographic spread of these tick species, as well as the effects of climate change on vector-borne diseases, it is timely to encourage research on diapause phenomena to improve understanding of their biology and of pathogen transmission dynamics. In our review we seek to clarify thinking on the topic and to address gaps in our knowledge that require the attention of researchers. PMID- 27263093 TI - Effect of acute hypoxic shock on the rat brain morphology and tripeptidyl peptidase I activity. AB - Hypoxic events are known to cause substantial damage to the hippocampus, cerebellum and striatum. The impact of hypoxic shock on other brain parts is not sufficiently studied. Recent studies show that tripeptidyl peptidase I (TPPI) activity in fish is altered after a hypoxic stress pointing out at a possible enzyme involvement in response to hypoxia. Similar studies are not performed in mammals. In this work, the effect of sodium nitrite-induced acute hypoxic shock on the rat brain was studied at different post-treatment periods. Morphological changes in cerebral cortex, cerebellum, medulla oblongata, thalamus, mesencephalon and pons were assessed using silver-copper impregnation for neurodegeneration. TPPI activity was biochemically assayed and localized by enzyme histochemistry. Although less vulnerable to oxidative stress, the studied brain areas showed different histopathological changes, such as neuronal loss and tissue vacuolization, dilatation of the smallest capillaries and impairment of neuronal processes. TPPI activity was strictly regulated following the hypoxic stress. It was found to increase 12-24h post-treatment, then decreased followed by a slow process of recovery. The enzyme histochemistry revealed a temporary enzyme deficiency in all types of neurons. These findings indicate a possible involvement of the enzyme in rat brain response to hypoxic stress. PMID- 27263094 TI - AGE-RAGE interaction in the TGFbeta2-mediated epithelial to mesenchymal transition of human lens epithelial cells. AB - Basement membrane (BM) proteins accumulate chemical modifications with age. One such modification is glycation, which results in the formation of advanced glycation endproducts (AGEs). In a previous study, we reported that AGEs in the human lens capsule (BM) promote the TGFbeta2-mediated epithelial-to-mesenchymal transition (EMT) of lens epithelial cells, which we proposed as a mechanism for posterior capsule opacification (PCO) or secondary cataract formation. In this study, we investigated the role of a receptor for AGEs (RAGE) in the TGFbeta2 mediated EMT in a human lens epithelial cell line (FHL124). RAGE was present in FHL124 cells, and its levels were unaltered in cells cultured on either native or AGE-modified BM or upon treatment with TGFbeta2. RAGE overexpression significantly enhanced the TGFbeta2-mediated EMT responses in cells cultured on AGE-modified BM compared with the unmodified matrix. In contrast, treatment of cells with a RAGE antibody or EN-RAGE (an endogenous ligand for RAGE) resulted in a significant reduction in the TGFbeta2-mediated EMT response. This was accompanied by a reduction in TGFbeta2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFbeta2-mediated EMT of lens epithelial cells and suggest that the blockade of RAGE could be a strategy to prevent PCO and other age associated fibrosis. PMID- 27263095 TI - Expedient synthesis of the pentasaccharide repeating unit of the O-antigen of Escherichia coli O86 and its conformational analysis. AB - Synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. The synthetic strategy involves sequential glycosylation of suitably protected monosaccharide intermediates under similar glycosylation reaction conditions. Thioglycosides have been used as glycosyl donor throughout the synthetic strategy. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique. Graphical abstract Facile synthesis of the pentasaccharide with a 2-aminoethyl linker attached to the reducing end corresponding to the cell wall O-antigen of Escherichia coli O86 strain is reported. Conformational analysis of the synthesized pentasaccharide has been carried out using 2D ROESY NMR spectral analysis and all atom explicit molecular dynamics (MD) simulation technique. PMID- 27263096 TI - Synthetic arabinomannan glycolipids impede mycobacterial growth, sliding motility and biofilm structure. AB - Mycobacterium has evolved distinct cell wall and strategies such as biofilm formation, which helps it to survive in hostile conditions. We have reported previously that arabinofuranoside containing glycolipids exhibit inhibition activities against the above functions of the mycobacterial species M. smegmatis. In search for activities mediated by oligosaccharide glycolipids, we report herein the inhibitory activities of a linear and a branched pentasaccharides having arabinan and mannan moieties. In the presence of the pentasaccharide glycolipids, a significant reduction in mycobacterial growth is observed, concomitant with reductions in sliding motility and colonization through biofilm formation, at the optimal glycolipid concentrations of 50-100 MUg mL(-1). Especially the biofilm coat is ruptured by ~80-85 % in the presence of glycolipids. Pentasaccharides alone without the lipidic chain show only a weak effect. The glycolipids are non-toxic, as evaluated through their effect on RBCs. Analysis of the mycolic acid profile of glycolipid treated biofilm shows that alpha- and epoxy mycolic acids are downregulated significantly, in comparison to glycolipid untreated biofilms. Lipidomics profile analysis through mass spectrometry further reveals profound downregulation of phosphatidylinositol mannosides, acylatedphosphoglycerols and mycolic acid family, namely, keto-, alpha- and methoxymycolic acids. PMID- 27263097 TI - Modified social learning theory re-examined: correlates of self-management behaviors of persons with Type 2 diabetes. AB - Modified social learning theory (MSLT) applied to health predicts that health behavior is a multiplicative function of health value and perceptions of control over health. The self-management behaviors of persons with Type 2 diabetes mellitus, internal diabetes locus of control (IDLC), diabetes self-efficacy (DSE), and health value (HV) were assessed with an index of diabetes self-care activities in 107 patients receiving insulin. Multiple regression analysis showed DSE as the only MSLT construct that correlated with the index of diabetes self care behaviors (beta = .21, p < .05). While the predicted three-way interaction of IDLC * DSE * HV was significant (?R2 = 4.5 %, p < .05) in the final step of the hierarchical model, the pattern of the findings only partially supported MSLT. Instead of finding that patients who were simultaneously high on all three predictors scored highest on the behavioral index, we found that patients who were low on all three constructs reported the least amount of diabetes self-care behavior. Implications for further modification of MSLT and its applications to clinical practice are discussed. PMID- 27263098 TI - Glucose levels affect LL-37 expression in monocyte-derived macrophages altering the Mycobacterium tuberculosis intracellular growth control. AB - Diabetes mellitus (DM)-2 patients have an increased susceptibility to develop pulmonary tuberculosis; this is partly due to the impairment of the innate immunity because of their higher glucose concentrations. In the present study, we determined the effect of the glucose concentrations in the LL-37 expression in infected and non-infected macrophages. Our results showed that the increasing glucose concentrations correlates with the low cathelicidin expression in non infected cells, however in Mycobacterium tuberculosis infected cells, LL-37 expression was substantially increased in higher glucose concentrations, nevertheless the mycobacterial burden also increased, this phenomena can be associated with the cathelicidin immunomodulatory activity. Further evaluation for LL-37 needs to be done to determine whether this peptide can be used as a biomarker of tuberculosis progression in DM2 patients. PMID- 27263100 TI - Climate Change and Ecosystem Services Output Efficiency in Southern Loblolly Pine Forests. AB - Forests provide myriad ecosystem services that are vital to humanity. With climate change, we expect to see significant changes to forests that will alter the supply of these critical services and affect human well-being. To better understand the impacts of climate change on forest-based ecosystem services, we applied a data envelopment analysis method to assess plot-level efficiency in the provision of ecosystem services in Florida natural loblolly pine (Pinus taeda L.) forests. Using field data for n = 16 loblolly pine forest plots, including inputs such as site index, tree density, age, precipitation, and temperatures for each forest plot, we assessed the relative plot-level production of three ecosystem services: timber, carbon sequestered, and species richness. The results suggested that loblolly pine forests in Florida were largely inefficient in the provision of these ecosystem services under current climatic conditions. Climate change had a small negative impact on the loblolly pine forests efficiency in the provision of ecosystem services. In this context, we discussed the reduction of tree density that may not improve ecosystem services production. PMID- 27263099 TI - Wildlife Conservation and Private Protected Areas: The Discrepancy Between Land Trust Mission Statements and Their Perceptions. AB - In 2010, land trusts in the U.S. had protected nearly 50 million acres of land, with much of it providing habitat for wildlife. However, the extent to which land trusts explicitly focus on wildlife conservation remains largely unknown. We used content analysis to assess land trust involvement in wildlife and habitat conservation, as reflected in their mission statements, and compared these findings with an organizational survey of land trusts. In our sample of 1358 mission statements, we found that only 17 % of land trusts mentioned "wildlife," "animal," or types of wildlife, and 35 % mentioned "habitat" or types. Mission statements contrasted sharply with results from a land trust survey, in which land trusts cited wildlife habitat as the most common and significant outcome of their protection efforts. Moreover, 77 % of land trusts reported that at least half of their acreage protected wildlife habitat, though these benefits are likely assumed. Importantly, mission statement content was not associated with the percentage of land reported to benefit wildlife. These inconsistencies suggest that benefits to wildlife habitat of protected land are recognized but may not be purposeful and strategic and, thus, potentially less useful in contributing toward regional wildlife conservation goals. We outline the implications of this disconnect, notably the potential omission of wildlife habitat in prioritization schema for land acquisition and potential missed opportunities to build community support for land trusts among wildlife enthusiasts and to develop partnerships with wildlife conservation organizations. PMID- 27263101 TI - Suicide attempt with a kitchen knife. AB - Penetrating trauma to the abdomen can be a potential diagnostic dilemma for the trauma surgeon, and a formal exploratory laparotomy may result in the detection of occult injuries. We report a very unusual case of penetrating trauma to the abdomen resulting in pericardio-diagphragmatic rupture. We have also highlighted the technical aspects of clinical care in this specific scenario. PMID- 27263102 TI - Stable isotope on the evaluation of water quality in the presence of WWTPs in rivers. AB - We investigated the distribution of nitrogen compounds in Han River as well as two tributaries of Tancheon and Jungrangcheon. Particularly, we observed the significant releases of NH4 (+)-N from effluent of wastewater treatment plants (WWTPs) in two tributaries that has resulted in the increases of ammonium nitrogen (NH4 (+)-N) in Han River as well as in Tancheon and Jungrangcheon. Due to the increases of NH4 (+)-N in two tributaries, the larger distribution of delta(15)N-NH4 (+) was observed than those of delta(15)N-NO3 (-) in downstream. We calculated the contribution rate of ammonium nitrogen and nitrate nitrogen from effluent to downstream according to the results of stable isotope. The contribution rates of delta(15)N-NH4 (+) from effluent to downstream were significant that ranged between 53 and 100 % in Tancheon and between 27 and 100 % in Jungrangcheon. While the contribution of delta(15)N-NO3 (-) was not significant in Tancheon, it was occasionally observed in Jungrangcheon. These results demonstrated that WWTPs are the major sources of NH4 (+)-N in two tributaries, which caused the distinguishable stable isotope of delta(15)N-NH4 (+). Therefore, the stable isotope of delta(15)N-NH4 (+) could be a useful parameter or tracer for the evaluation of NH4-N released from WWTPs in rivers. PMID- 27263103 TI - Combination of antibiotics suppressed the increase of a part of ARGs in fecal microorganism of weaned pigs. AB - The presence of antibiotic resistance genes (ARGs) is one of the most important public health concerns. Six tetracycline resistance genes (TRGs-tetA, tetC, tetL, tetO, tetW, and tetX) were quantified using real-time quantitative polymerase chain reaction (qPCR) in the fecal microorganisms of weaned pigs. Two hundred 35 day-old weaned pigs were fed different dietary antibiotics for 28 days: (1) no antibiotic as the control treatment (CT); (2) chlortetracycline, bacitracin zinc and colistin sulfate (CBC); (3) bacitracin zinc and colistin sulfate (BC); and (4) chlortetracycline (CTC). The detection frequencies (DFs) of tetC, tetL, and tetW were 100 %; and the DFs of tetA, tetD, tetM, tetO, and tetX were 65 %. The relative abundances (tet/16S rRNA gene copy numbers) of six tet genes (tetA, tetC, tetL, tetO, tetW and tetX) were between 1.5 * 10(-4) and 2.0 * 10(-1). In the group CTC, the relative abundances of tetC (P < 0.01), tetL (P < 0.01), tetO (P < 0.05), tetW (P < 0.01), and tetX (P < 0.01) were greater than those of the group CT. Compared with the group CTC, the relative abundances of tetC (P < 0.01), tetL (P < 0.01), and tetW (P < 0.01) were decreased in the CBC and BC groups. These results indicate that a combination of different antibiotics suppressed the abundance increase of a part of tet genes, which suggests that a combination of antibiotics produces multiple selection pressures on fecal microorganism of pigs. PMID- 27263104 TI - Allelopathic potential of oil seed crops in production of crops: a review. AB - Agricultural production enhancement has been realized by more consumption of fossil energy such as fertilizer and agrochemicals. However, the production provides the present human with sufficient and diversified commodities, but at the same time, deprives in some extent the resources from the future human as well. In the other hand, it is known that synthetic herbicides face worldwide threats to human's health and environment as well. Therefore, it is a great challenge for agricultural sustainable development. The current review has been focussed on various oilseed crop species which launch efficient allelopathic intervention, either with weeds or other crops. Crop allelopathic properties can make one species more persistent to a native species. Therefore, these crops are potentially harmful to both naturalized as well as agricultural settings. On the other side, allelopathic crops provide strong potential for the development of cultivars that are more highly weed suppressive in managed settings. It is possible to utilize companion plants that have no deleterious effect on neighbor crops and can be included in intercropping system, thus, a mean of contributing to agricultural sustainable development. In mixed culture, replacement method, wherein differing densities of a neighbor species are planted, has been used to study phytotoxic/competitive effects. So, to use alternative ways for weed suppression has become very crucial. Allelochemicals have the ability to create eco-friendly products for weed management, which is beneficial for agricultural sustainable development. Our present study assessed the potential of four oilseed crops for allelopathy on other crops and associated weeds. PMID- 27263105 TI - Constructed wetlands may lower inorganic nutrient inputs but enhance DOC loadings into a drinking water reservoir in North Wales. AB - The objective of this study was to monitor a newly constructed wetland (CW) in north Wales, UK, to assess whether it contributes to an improvement in water quality (nutrient removal) of a nearby drinking water reservoir. Inflow and outflow of the Free Water Surface (FWS) CW were monitored on a weekly basis and over a period of 6 months. Physicochemical parameters including pH, conductivity and dissolved oxygen (DO) were measured, as well as nutrients and dissolved organic and inorganic carbon (DOC, DIC) concentration. The CW was seen to contribute to water quality improvement; results show that nutrient removal took place within weeks after construction. It was found that 72 % of initial nitrate (N03 (-)), 53 % of initial phosphate (PO4 (3-)) and 35 % of initial biological oxygen demand (BOD) were removed, calculated as a total over the whole sampling period. From our study, it can be concluded that while inorganic nutrients do decline in CWs, the DOC outputs increases. This may suggest that CWs represent a source for DOC. To assess the carbon in- and output a C budget was calculated. PMID- 27263106 TI - Surgical outcome of patients with lung cancer involving the left atrium. AB - BACKGROUND: Pulmonary and left atrial resection is not yet an established treatment for patients with primary lung cancer involving the left atrium. We investigated the clinical course of patients with primary lung cancer involving the left atrium who were treated with pulmonary resection and partial atrial resection. METHODS: From January 1996 to December 2013, 51 patients underwent extended resection for lung cancer that invaded the surrounding organs. Of these, we focused on 12 patients who underwent surgical treatment for lung cancer involving the left atrium. The clinical course of each of these patients was investigated retrospectively. RESULTS: The most common histological subtype was squamous cell carcinoma. Pneumonectomy was performed in nine patients, and right middle and lower lobectomy was performed in three patients. Complete resection was performed in 11 patients (92 %). Postoperative complications were observed in four patients (33 %)-prolonged air leakage in two patients, broncho-pleural fistula in one patient, and empyema in one patient. There were no surgical deaths. This study involved seven patients with pathological N0-1 disease and five patients with pathological N2 disease. The postoperative 5-year survival rate was 46 % in all patients. The 5-year survival rates in patients with pathological N0-1 disease and N2 disease were 67 and 20 %, respectively. CONCLUSION: Because treatment-related death was not observed and outcome was fair in patients with N0-1 disease, surgical resection for primary lung cancer involving the left atrium may be acceptable in selected patients. Further investigations are required to improve the outcome of surgical treatment for patients with primary lung cancer involving the left atrium. PMID- 27263107 TI - High incidence of urological complications in men dying from prostate cancer. AB - BACKGROUND: The incidence and clinical characteristics of urological adverse events suffered by patients with lethal prostate cancer (PCa) toward the end of life are not fully understood. METHODS: A search of our hospital medical registry identified 3816 individuals diagnosed with PCa, among whom 243 died from the disease and 144 died from other causes (n = 387). We retrospectively reviewed the 387 patients who had died to determine the incidence of PCa-related urological complications, associated factors, and subsequent palliative interventions. RESULTS: Major urological complications that required therapeutic intervention were observed in 28.4 % of PCa patients dying from the disease itself, whereas such complications were much less frequent (4.3 %) in PCa patients dying from other causes. Urological complications were associated with local recurrence in men who underwent prostatectomy, lower irradiation dose in men who underwent radiotherapy, and pretreatment higher T stage and absence of metastasis in men who underwent androgen deprivation therapy (ADT) as the primary treatment. Patients who received long-term ADT for localized disease had the highest risk for urological complications. Therapeutic intervention was highly effective for palliation. CONCLUSION: Urological adverse events are very common in PCa patients who are dying from the disease. Prevention or early palliation should be considered in patients at high risk of PCa-related urological complications. PMID- 27263109 TI - A Single-Nucleotide Polymorphism in C12orf43 Region is Associated with the Risk of Coronary Artery Disease in a Pakistani Cohort. AB - Coronary artery disease (CAD) is one of the leading public health problems associated with mortality and morbidity in the world. It is a complex disorder influenced by both genetic and environmental factors. Atherosclerosis and elevated levels of plasma cholesterol contribute to increased risk for CAD. Other risk factors include age, hypertension, obesity, diabetes, smoking, and family history. Previous genetic studies have identified multiple polymorphisms in various genes to be associated with the risk of CAD in different populations. We aimed to examine the association of MRAS/rs9818870 and C12orf43/rs2258287 polymorphisms with the risk of CAD in a Pakistani sample. A total of 200 samples (100 cases and 100 controls) was analyzed by Allele-specific PCR. Genotypes were determined by agarose gel electrophoresis. In the current study, locus C12orf43/rs2258287 was found to be associated with the risk of CAD in the studied Pakistani cohort (OR 0.18; CI 0.08-0.37; p = 0.0001) while no association was observed for MRAS/rs9818870 (OR 1.34; CI 0.65-2.76; p = 0.42). In conclusion, the rs2258287 SNP may play an important role in the progression of CAD in the Pakistani subjects. However, future studies should be done on a larger sample size to fully establish its exact role in CAD. PMID- 27263110 TI - Is age an independent risk factor for medical complications following minimally invasive radical prostatectomy? An evaluation of contemporary American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) data. AB - While robotic-assisted laparoscopic radical prostatectomy (RALRP) is an effective treatment for localized prostate cancer, the risk of complications in older patients can be a deterrent to surgery. We evaluated the rate of medical complications following RALRP in a national dataset of safety events, and assessed whether age is an independent risk factor for these complications. Retrospective analysis of patients undergoing RALRP between 2009 and 2012 in the prospectively maintained American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) database was performed. Demographic and comorbid data were collated, medical complications occurring during the 30-day post-operative period were identified. We identified age-related comorbidities, and complications associated with these comorbidities. A binary logistic regression model with age and age-related comorbidities as predictors and specific complication as outcome, was used to evaluate whether age is an independent risk factor for these complications. 12,123 patients underwent RALRP between 2009 and 2012, with a mean age of 62 (22-92). Post-operative medical complications included urinary tract infection (UTI) (1.77 %), deep venous thrombosis (DVT) (0.67 %), pulmonary embolism (PE) (0.45 %), pneumonia (PNA) (0.27 %), myocardial infarction (MI) (0.12 %), and cerebrovascular accident (CVA) (0.01 %). Nine comorbidities were positively correlated with age (p < 0.05). Four medical complications were associated with these age-related comorbidities: MI, CVA, PNA, and UTI. On multivariate analysis, age was an independent risk factor for post operative PNA (p < 0.05), but not for MI (p = 0.09), UTI (p = 0.3) or CVA (p = 0.2). Patient age was independently associated with post-operative pneumonia only. These data suggest that RALRP can be considered as a treatment option in selected older patients with minimal increased risk for post-operative complications. PMID- 27263108 TI - Tissue-Level Mechanical Properties of Bone Contributing to Fracture Risk. AB - Tissue-level mechanical properties characterize mechanical behavior independently of microscopic porosity. Specifically, quasi-static nanoindentation provides measurements of modulus (stiffness) and hardness (resistance to yielding) of tissue at the length scale of the lamella, while dynamic nanoindentation assesses time-dependent behavior in the form of storage modulus (stiffness), loss modulus (dampening), and loss factor (ratio of the two). While these properties are useful in establishing how a gene, signaling pathway, or disease of interest affects bone tissue, they generally do not vary with aging after skeletal maturation or with osteoporosis. Heterogeneity in tissue-level mechanical properties or in compositional properties may contribute to fracture risk, but a consensus on whether the contribution is negative or positive has not emerged. In vivo indentation of bone tissue is now possible, and the mechanical resistance to microindentation has the potential for improving fracture risk assessment, though determinants are currently unknown. PMID- 27263111 TI - Protective Effects of AGE and Its Components on Neuroinflammation and Neurodegeneration. AB - Garlic (Allium sativum) is used for culinary and medicinal purposes in diverse cultures worldwide. When fresh garlic is soaked in aqueous ethanol under ambient environment over 4 months or longer, the majority of irritating taste and odor is eliminated and the antioxidant profile in the resulting aged garlic extract (AGE) changes significantly. Recently, AGE and its components have been demonstrated to exert neuroprotective effects in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and cerebral ischemia. Because of its health supporting potential, there is increasing interest in understanding the antioxidant and anti-inflammatory properties and the underlying mechanisms for its protective effects in heath and disease. There is evidence for AGE to exert its action on distinct signaling pathways associated with oxidative stress and neuroinflammation, although the primary molecular mechanisms remain unclear. By utilizing quantitative proteomic approaches, we demonstrated that AGE and two of its major ingredients, S-allyl-L-cysteine and N (alpha)-(1-deoxy-D-fructos-1-yl)-L-arginine, can attenuate neuroinflammatory responses in microglial cells through modulation of Nrf2-mediated signaling as well as other oxidative stress-related pathways. These experimental data provide information for the molecular targets of AGE and its components to mitigate neurodegeneration and neuroinflammation and show a promising potential of these compounds as dietary supplements for health maintenance. PMID- 27263113 TI - Iron plaque formed under aerobic conditions efficiently immobilizes arsenic in Lupinus albus L roots. AB - Arsenic is a non-threshold carcinogenic metalloid. Thus, human exposure should be minimised, e.g. by chemically stabilizing As in soil. Since iron is a potential As immobiliser, it was investigated whether root iron plaque, formed under aerobic conditions, affects As uptake, metabolism and distribution in Lupinus albus plants. White lupin plants were cultivated in a continuously aerated hydroponic culture containing Fe/EDDHA or FeSO4 and exposed to arsenate (5 or 20 MUM). Only FeSO4 induced surficial iron plaque in roots. LA-ICP-MS analysis accomplished on root sections corroborated the association of As to this surficial Fe. Additionally, As(V) was the predominant species in FeSO4-treated roots, suggesting less efficient As uptake in the presence of iron plaque. Fe/EDDHA-exposed roots neither showed such surficial FeAs co-localisation nor As(V) accumulation; in contrast As(III) was the predominant species in root tissue. Furthermore, FeSO4-treated plants showed reduced shoot-to-root As ratios, which were >10-fold lower compared to Fe/EDDHA treatment. Our results highlight the role of an iron plaque formed in roots of white lupin under aerobic conditions on As immobilisation. These findings, to our knowledge, have not been addressed before for this plant and have potential implications on soil remediation (phytostabilisation) and food security (minimising As in crops). PMID- 27263114 TI - Antigen uptake and expression of antigen presentation-related immune genes in flounder (Paralichthys olivaceus) after vaccination with an inactivated Edwardsiella tarda immersion vaccine, following hyperosmotic treatment. AB - Antigen uptake is a critical process for activation of the immune system, and therefore the ability to enhance antigen uptake is a primary consideration in the development of an immersion vaccination of fish. In the present work, flounders (Paralichthys olivaceus) were immersed in three hyperosmotic solutions with 40, 50 and 600/00 salinities, then transferred into seawater of normal salinity (i.e. 300/00) containing formalin-inactivated Edwardsiella tarda for 30 min. The antigen uptake in vaccinated flounder was determined using an absolute quantitative PCR (qPCR). The results showed significantly higher antigen uptake in the tissues of flounders immersed in solutions with 500/00 and 600/00 salinity compared to the control group directly immersed in vaccine (DI) (P < 0.05), and the highest amount of antigen was detected in flounders immersed in the 500/00 salinity solution, whereas there was no significant difference in antigen uptake between the 400/00 salinity group and the DI group (P > 0.05). A rapid and significant increase in antigen uptake was detected in the mucosal-associated tissues including the gill, skin and intestine (P < 0.05) compared with the spleen, kidney and liver. Antigen uptake in the gill and skin both peaked at 30 min post immersion, which was significantly higher than the levels of uptake measured in the other tissues (P < 0.05), and then quickly declined. In contrast, antigen uptake in the spleen, kidney and liver gradually increased 3 h post immersion (hpi). The expression profiles of four antigen presentation-related immune genes (MHC Ialpha, MHC IIalpha, CD4-1 and CD8alpha) were investigated after immersion. These four genes showed a significantly stronger response in the immersed flounders exposed to 500/00 salinity compared with the DI group (P < 0.05). In the mucosal-associated tissues, the expression of MHC Ialpha and CD8alpha genes peaked at 24 hpi, while the expression of MHC IIalpha and CD4-1 genes showed up-regulation in the gill and skin and reached the peak in these tissues at 48 hpi. The expressions of the four genes were also up-regulated in spleen, kidney and liver, but reached peak expression in these tissues at 48-72 hpi. The results demonstrated that hyperosmotic immersion, notably 500/00 salinity significantly enhanced antigen uptake and the expression of selected genes associated with antigen presentation, providing evidence for an enhanced immune activation of the fish's immune response by the hyperosmotic immersion treatment prior to vaccination. PMID- 27263112 TI - mTOR Signaling in Parkinson's Disease. AB - As a key regulator of cell metabolism and survival, mechanistic target of rapamycin (mTOR) emerges as a novel therapeutic target for Parkinson's disease (PD). A growing body of research indicates that restoring perturbed mTOR signaling in PD models can prevent neuronal cell death. Nevertheless, molecular mechanisms underlying mTOR-mediated effects in PD have not been fully understood yet. Here, we review recent progress in characterizing the association of mTOR signaling with PD risk factors and further discuss the potential roles of mTOR in PD. PMID- 27263115 TI - Toll-like receptors and interferon associated immune factors responses to spring viraemia of carp virus infection in common carp (Cyprinus carpio). AB - Pattern recognition receptor (PRR) toll-like receptors (TLRs), antiviral agent interferon (IFN) and the effector IFN stimulated genes (ISGs) play a fundamental role in the innate immune response against viruses among all vertebrate classes. Common carp is a host for spring viraemia of carp virus (Rhabdovirus carpio, SVCV), which belong to Rhabdoviridae family. The present in-vivo experiment was conducted to investigate the expression of these innate immune factors in early phase as well as during recovery of SVCV infection by real-time quantitative reverse transcriptase polymerase chain reaction. A less lethal SVCV infection was generated in common carp (Cyprinus carpio) and was sampled at 3, 6, 12 h post infection (hpi), 1, 3, 5, 7 and 10 days post infection (dpi). At 3 hpi, the SVCV N gene was detected in all three fish and all three fish showed a relative fold increase of TLR2, TLR3 and TLR7, IFNa1, ISG15 and Vig1. Viral copies rapidly increased at 12 hpi then remained high until 5 dpi. When viral copy numbers were high, a higher expression of immune genes TLR2, TLR3, TLR7, IFNa1, IFNa2, IFNa1S, IFN regulatory factor 3 (IRF3), IRF7, interleukin 1beta (IL1beta), IL6, IL10, ADAR, ISG15, Mx1, PKR and Vig1 were observed. Viral copies were gradually reduced in 5 to 10 dpi fish, and also the immune response was considerably reduced but remained elevated. A high degree of correlation was observed between immune genes and viral copy number in each of the sampled fish at 12 hpi. The quick and prolonged elevated expression of the immune genes indicates their crucial role in survival of host against SVCV. PMID- 27263117 TI - Psychological distress among adult cancer survivors: importance of survivorship care plan. AB - PURPOSE: The goal of our study was to better understand the importance of adult cancer survivors (ACS) receiving Survivorship Care Plans (SCP) especially for their psychological well-being. We hypothesize that the receipt of SCP would decrease the likelihood of symptoms of current depression (SCD) in this population. METHODS: We tested our hypothesis by using a representative sample of ACS, more than 1 year from cancer diagnosis, who responded to the 2010 BRFSS survey. We used follow-up care instructions (FCI) and treatment summaries (TS) as a marker of SCP. Weighted multivariable logistic regression models were used to investigate the association between FCI and TS (individually and in combination) and SCD, among short-term (<=5 years from cancer diagnosis) and long-term (>5 years from cancer diagnosis) ACS. RESULTS: Out of 3191 final study participants, 32.8 % were short-term, and 67.2 % were long-term ACS. Among short-term ACS, the adjusted odds of SCD were 3 times higher (adjusted odds ratio (AOR) 3.14 [95%CI 1.29-7.65]) for those who did not receive TS + FCI than for those who received them both. Among long-term ACS, the adjusted odds of SCD were more than twice higher (AOR 2.18 [95%CI 1.14-4.19]) for those who received FCI and no TS compared to those who received them both. CONCLUSION: The present study results emphasize the importance of ACS receiving SCP. Adult cancer survivors may highly benefit from the receipt of SCP not only short-term but also long-term for their overall psychological well-being. PMID- 27263118 TI - Is the treatment of Enterobius vermicularis co-infection necessary to eradicate Dientamoeba fragilis infection? AB - OBJECTIVES: Dientamoeba fragilis is a pathogenic protozoan of the human gastrointestinal tract with a worldwide distribution, which has emerged as an important and misdiagnosed cause of chronic gastrointestinal illnesses such as diarrhea and 'irritable-bowel-like' gastrointestinal disease. Very little research has been conducted on the use of suitable antimicrobial compounds. Furthermore, higher rates of co-infection with Enterobius vermicularis have been described, suggesting that E. vermicularis could influence the treatment of D. fragilis-infected patients. To study this, the treatment of E. vermicularis and D. fragilis co-infected patients was evaluated. METHODS: Forty-nine patients with a D. fragilis infection, including 25 (51.0%) patients co-infected with E. vermicularis, were studied. All of them were treated with metronidazole. Patients with E. vermicularis co-infection and/or an E. vermicularis-positive case in the family were treated with mebendazole. RESULTS: Metronidazole treatment failure was significantly more frequent in patients with E. vermicularis co-infection and in patients with children in the family. CONCLUSIONS: Co-infection with E. vermicularis may act as a factor favoring D. fragilis infection by preventing eradication measures. This suggests that both parasites should be treated simultaneously. PMID- 27263119 TI - [Skin necrosis with vitamin K antagonists: An imbalance between coagulant and anticoagulant factors]. AB - INTRODUCTION: Skin necrosis with vitamin k antagonists are rare. They affect more frequently middle-aged and obese women, often within 10 days after initiating of treatment. They occur most often in a context of thrombophilia. CASE REPORT: An 18-year-old obese woman was treated with heparin and fluindione for a lower limb deep venous thrombosis. On day 5, the patient presented fever and skin necrosis, which extended rapidly. We identified an activated protein C resistance and a major inflammatory syndrome related to Mycoplasma pneumoniae infection. The outcome was favorable after discontinuation of the fluindione, introduction of heparin and vitamin K, despite amputation of a toe. CONCLUSION: Skin necrosis is due to a transient hypercoagulable state during the initiation of vitamin K antagonist treatment due to an imbalance between pro- and anticoagulant factors. In our case, it was caused by an activated protein C resistance and an inflammatory syndrome. PMID- 27263121 TI - [Potential use of bacteriophages in modern infectiology]. PMID- 27263120 TI - [Off-label use of intravenous immunoglobulin therapy in the treatment of lupus myocarditis: Two case reports and literature review]. AB - INTRODUCTION: Several case reports have reported the benefit of intravenous immunoglobulin therapy in many autoimmune diseases, including systemic lupus erythematosus. CASE REPORTS: Here, we report on two cases of lupus myocarditis treated with high dose of intravenous immunoglobulin. The first patient was a 42 year-old woman who presented with lupus myocarditis that was resistant to corticosteroids and cyclophosphamide, and who was finally successfully treated with a single dose of 2 g/kg of intravenous immunoglobulin. The patient displayed clinical improvement a few days later. The second case - a 43-year-old woman was diagnosed with lupus myocarditis and immunosuppressive drugs were contraindicated because of the context of a recent infective endocarditis. She was treated with repeated dose of 2 g/kg of intravenous immunoglobulin. Clinical improvement was observed and the left ventricular ejection fraction increased from 20 % to 60 % within a few days. We also report 9 similar observations identified from a literature review. CONCLUSION: The use of intravenous immunoglobulin in lupus myocarditis is not officially recognized but could be considered as an alternative when conventional therapies have failed or are contraindicated. PMID- 27263116 TI - Life in a dark biosphere: a review of circadian physiology in "arrhythmic" environments. AB - Most of the life with which humans interact is exposed to highly rhythmic and extremely predictable changes in illumination that occur with the daily events of sunrise and sunset. However, while the influence of the sun feels omnipotent to surface dwellers such as ourselves, life on earth is dominated, in terms of biomass, by organisms isolated from the direct effects of the sun. A limited understanding of what life is like away from the sun can be inferred from our knowledge of physiology and ecology in the light biosphere, but a full understanding can only be gained by studying animals from the dark biosphere, both in the laboratory and in their natural habitats. One of the least understood aspects of life in the dark biosphere is the rhythmicity of physiology and what it means to live in an environment of low or no rhythmicity. Here we describe methods that may be used to understand rhythmic physiology in the dark and summarise some of the studies of rhythmic physiology in "arrhythmic" environments, such as the poles, deep sea and caves. We review what can be understood about the adaptive value of rhythmic physiology on the Earth's surface from studies of animals from arrhythmic environments and what role a circadian clock may play in the dark. PMID- 27263122 TI - Paradigms in the structural biology of the mitogenic ternary complex FGF:FGFR:heparin. AB - The main achievements regarding the molecular interaction involving fibroblast growth factors (FGFs), canonical receptors (FGFRs) and the glycosaminoglycans (GAGs) heparan sulfate (HS)/heparin (Hp) are overviewed. Despite the recent works concerning the subject, conflicting paradigms in the structural biology of the resultant ternary complex FGF:FGFR:HS/Hp seem to persist up to these days. The principal dilemma, centered on the functional intermolecular complex of mitogenesis and angiogenesis, has been lasting for approximately a decade and a half since the publications of the two contradicting crystal structures, the asymmetric 2:2:1 versus the symmetric 2:2:2 complex model. When the principal results regarding this ternary complex are analyzed as a whole and through an impartial manner, conclusion heavily and reliably supports the existence and activity of both complex models. Selection of each complex is driven by multiple factors of different degrees of impact. Specificity in protein-binding motifs in ligands (although the minimal binding sequences are yet controversial), slight differences on the structure of the GAG-binding sites of FGF and of FGFR isoforms as well as on the possible ligand-induced conformational changes of FGFR are examples of these factors. Here, the structural biology of the mitogenic FGF:FGFR:HS/Hp ternary complex is revisited. Discussion is focused on the major attributes of this intermolecular complex including the existing conflicts about the righter biologically active model and information regarding ligand structure, conformation and minimal length required for binding to the growth factors and receptors. This review is very timely in light of the 100(th) anniversary of the discovery of Hp. PMID- 27263123 TI - Native language shapes automatic neural processing of speech. AB - The development of the phoneme inventory is driven by the acoustic-phonetic properties of one's native language. Neural representation of speech is known to be shaped by language experience, as indexed by cortical responses, and recent studies suggest that subcortical processing also exhibits this attunement to native language. However, most work to date has focused on the differences between tonal and non-tonal languages that use pitch variations to convey phonemic categories. The aim of this cross-language study is to determine whether subcortical encoding of speech sounds is sensitive to language experience by comparing native speakers of two non-tonal languages (French and English). We hypothesized that neural representations would be more robust and fine-grained for speech sounds that belong to the native phonemic inventory of the listener, and especially for the dimensions that are phonetically relevant to the listener such as high frequency components. We recorded neural responses of American English and French native speakers, listening to natural syllables of both languages. Results showed that, independently of the stimulus, American participants exhibited greater neural representation of the fundamental frequency compared to French participants, consistent with the importance of the fundamental frequency to convey stress patterns in English. Furthermore, participants showed more robust encoding and more precise spectral representations of the first formant when listening to the syllable of their native language as compared to non-native language. These results align with the hypothesis that language experience shapes sensory processing of speech and that this plasticity occurs as a function of what is meaningful to a listener. PMID- 27263125 TI - Luteinizing Hormone is an effective replacement for hCG to induce ovulation in Xenopus. AB - Injection of human Chorionic Gonadotropin (hCG) directly into the dorsal lymph sac of Xenopus is a commonly used protocol for induction of ovulation, but recent shortages in the stocks of commercially available hCG as well as lack of a well tested alternative have resulted in frustrating experimental delays in laboratories that predominantly use Xenopus in their research. Mammalian Luteinizing Hormones (LH) share structural similarity, functional equivalency, and bind the same receptor as hCG; this suggests that LH may serve as a good alternative to hCG for promoting ovulation in Xenopus. LH has been found to induce maturation of Xenopus oocytes in vitro, but whether it can be used to induce ovulation in vivo has not been examined. Here we compared the ability of four mammalian LH proteins, bovine (bLH), human (hLH), ovine (oLH), porcine (pLH), to induce ovulation in Xenopus when injected into the dorsal lymph sac of sexually mature females. We find that both ovine and human LH, but not bovine or porcine, are good substitutes for hCG for induction of ovulation in WT and J strain Xenopus laevis and Xenopus tropicalis. PMID- 27263124 TI - Testing the domain-general nature of monitoring in the spatial and verbal cognitive domains. AB - While it is well-established that monitoring the environment for the occurrence of relevant events represents a key executive function, it is still unclear whether such a function is mediated by domain-general or domain-specific mechanisms. We investigated this issue by combining event-related potentials (ERPs) with a behavioral paradigm in which monitoring processes (non-monitoring vs. monitoring) and cognitive domains (spatial vs. verbal) were orthogonally manipulated in the same group of participants. They had to categorize 3 dimensional visually presented words on the basis of either spatial or verbal rules. In monitoring blocks, they additionally had to check whether the word displayed a specific spatial configuration or whether it contained a certain consonant. The behavioral results showed slower responses for both spatial and verbal monitoring trials compared to non-monitoring trials. The ERP results revealed that monitoring did not interact with domain, thus suggesting the involvement of common underlying mechanisms. Specifically, monitoring acted on low-level perceptual processes (as expressed by an enhanced visual N1 wave and a sustained posterior negativity for monitoring trials) and on higher-level cognitive processes (involving larger positive modulations by monitoring trials over frontal and parietal scalp regions). The source reconstruction analysis of the ERP data confirmed that monitoring was associated with increased activity in visual areas and in right prefrontal and parietal regions (i.e., superior and inferior frontal gyri and posterior parietal cortex), which previous studies have linked to spatial and temporal monitoring. Our findings extend this research by supporting the domain-general nature of monitoring in the spatial and verbal domains. PMID- 27263126 TI - A scoring system for predicting the survival prognosis of patients receiving stereotactic body radiation therapy (SBRT) for 1-3 lung metastases. AB - INTRODUCTION: The main goal of the present study was the development of a survival scoring system for patients treated with stereotactic body radiation therapy (SBRT) for very few lung metastases. Such an instrument would be of value when selecting the optimal dose for individual patients with a limited number of pulmonary lesions. METHODS: Forty-six patients receiving SBRT for 1-3 lung metastases were retrospectively analyzed. The biologically effective dose plus nine characteristics [gender, age, performance score, interval from tumor diagnosis to SBRT, primary tumor type, additional (extra-pulmonary) metastases, major location of lung metastases, number of pulmonary lesions, and volume treated with SBRT] were evaluated. Characteristics significantly associated with the survival on Cox regression analysis were incorporated in the scoring system. Scoring points were received from 1-year survival rates divided by 10. Sums of these scoring points represented the scores for the individual patients. RESULTS: Survival rates at 1 and 2 years were 66 and 56 %, respectively. On Cox regression analysis, performance score (p = 0.025), the type of primary tumor (p = 0.013) and the additional metastases (p = 0.032) had a significant impact on survival. Scores for patients ranged from 15 to 25 points. Three groups were designed: 15 points, 16-20 points, and 21-25 points. One-year survival rates were 0, 52, and 83 %, respectively (p = 0.005); 2-year survival rates were 0, 52, and 66 %, respectively. CONCLUSION: A survival scoring system for patients receiving SBRT for very few lung metastases was developed. This score allowed us to estimate the survival prognosis of these patients and can aid physicians when aiming to choose the optimal SBRT dose for individual patients. PMID- 27263127 TI - Epidemic focus: Influenza. PMID- 27263128 TI - Leishmaniasis in high-burden countries: an epidemiological update based on data reported in 2014. PMID- 27263129 TI - [Not Available]. PMID- 27263130 TI - [Not Available]. PMID- 27263131 TI - [Not Available]. PMID- 27263132 TI - Hemorrhage Control Beyond the Traditional Audiences: Instructions for Authors. PMID- 27263133 TI - Rob Miller on Changing Trauma Care. PMID- 27263134 TI - Evidence appraisal of Waljee J, McGlinn EP, Sears ED, Chung KC. Patient expectations and patient-reported outcomes in surgery: a systematic review: Surgery. 2014;155(5):799-808. PMID- 27263135 TI - Retraction notice to "Sequence variability in the structural protein-encoding region of foot-and-mouth disease virus serotype A and O of Ethiopian isolates" [Res. Vet. Sci. Volume 96, Issue 3, June 2014, Pages 558-566]. PMID- 27263136 TI - It's Important to Be Aware of Antitrust Law; What You Must Know to Keep Out of Trouble. PMID- 27263137 TI - Corporate dentistry's merits debated. PMID- 27263138 TI - Dr. Nalliah responds. PMID- 27263140 TI - Should My Employees Help Write Our Employee Handbook? PMID- 27263139 TI - What You Should Know about Unpaid Internships in Your Office. PMID- 27263141 TI - An Unethical Way to Compensate for Lower Insurance Plan Fees. PMID- 27263142 TI - LIFE AFTER DENTISTRY: 10 Personal Questions to Consider. PMID- 27263143 TI - Non-Hodgkin's Lymphoma in the Oral Cavity. AB - We report a case of a diffuse large B-cell lymphoma of the maxilla. A patient presented with diffuse swelling of the right maxillary region following the extraction of an upper right maxillary tooth. The patient was referred for cone beam computed tomography (CBCT) to visualize the area in question in three dimensions. A massive destructive maxillary lesion was noted on CBCT examination suggestive of an aggressive lesion highly suspicious for a malignancy. A subsequent biopsy and immunochemistry were useful in confirming the diagnosis. PMID- 27263144 TI - Oral Pathology. Common Oral Gingival Lesions. Diagnosis: Peripheral ossifying fibroma. PMID- 27263145 TI - Dentistry's Future: A Dental Student's Perspective. PMID- 27263146 TI - [Not Available]. PMID- 27263147 TI - [Outpatient parenteral antibiotic therapy (OPAT): the Lausanne experience supporting new perspectives]. AB - With the increase of infections without option for an oral treatment, the systematic use of hospitalization overloads the healthcare system and causes growing political concern. For carefully selected patients, outpatient parenteral antibiotic therapy is an interesting alternative, with more than 40 years of experience in several countries. In this perspective, an outpatient parenteral antibiotic therapy (OPAT) unit was established in Lausanne two years ago. This article aims to describe its activity. Its practice, involving especially self administration, seems to be safe, efficacious and cost-effective, as long as international good practice recommendations are applied. PMID- 27263148 TI - [Microbiology and antibiotic treatment of diabetic foot infection]. AB - In diabetic patients, foot ulcer is a common problem which prevalence during life is about 25%. Infection occurs as a complication in almost 50% of cases, is associated with significant morbidity and a reduced quality of life and is sometimes the trigger leading to amputation. Ulcers and infections occur among patients with predisposing factors such as peripheral neuropathy and arterial insufficiency, and require a multi-disciplinary care system. The knowledge of the microbiology of diabetic foot infection is necessary for a wise use of empirical and targeted antibiotic therapy. This article will focus on the definition and diagnosis of diabetic foot infection, on the main aspects of its microbiology and antibiotic treatment. PMID- 27263149 TI - [Varicella Zoster infections in adults: beyond shingles?]. AB - Chickenpox is a generally benign condition during childhood, but it can cause severe complications when affecting teenage or adult patients. Immunodeficiency and pregnancy are risk factors for disseminated disease with pulmonary, neurological and/or hepatic involvement. Reinfection may be more frequent than previously thought, and management is identical to that of primary infection. The most common manifestation of viral reactivation is shingles, but it can also cause meningitis and vasculopathy, as well as disseminated herpes zoster in the immunocompromised patient. In this article, we will review the clinical manifestations and management of VZV infection in adults. PMID- 27263150 TI - [Antimicrobial stewardship in primary care setting]. AB - Antibiotic overuse in primary care setting is a major contributor to the development of resistant bacteria. Antibiotic consumption is low in Switzerland compared to neighbour countries, but improvement is possible and has to be pursued. Antibiotic stewardship helps physician to better recognize patients who need antibiotic (guidelines implementation, electronic decision support and laboratory testing) and educate patients about the uselessness of antibiotics in a given situation (delayed prescription and shared decision making). Clinical studies demonstrated the efficacy of these interventions in reducing antibiotic consumption, mainly in acute respiratory infections, without affecting patients' clinical outcome. PMID- 27263151 TI - [European migrant crisis and reemergence of infections in Switzerland]. AB - Current conflicts in some regions of the world give rise to massive immigration waves. Consequently, some infections that had nearly disappeared in Europe nowadays re-emerge. They are related to the epidemiology of the refugees' origin, but also to the epidemiology of the country crossed during migration. Hygiene conditions, often precarious during the journey, favor their transmission. Thus, cases of louse borne relapsing fever and diphtheria emerge in Europe and in Switzerland since 2074 whereas cutaneous Panton-Valen tine Staphylococcus aureus infection are more commonly observed nowadays. PMID- 27263152 TI - [Clostridia: toxin masters. Botulism: from botox to sausages?]. AB - Clostridia are ubiquitous Gram-positive bacteria whose toxins are responsible for serious diseases. In this article we report a case of foodborne botulism we have recently managed. Moreover, we briefly describe the major clinical syndromes caused by different species of Clostridium (except for C. difficile infections, as this subject has been previously extensively reviewed in this journal). Botulism causes a flaccid paralysis starting with cranial nerves. Administration of botulism anti-toxin should be rapidly considered as soon as botulism is suspected, as prognosis is largely dependent on timely treatment; alerting the public health authorities is equally important. In Switzerland botulinum antitoxin can be obtained from the pharmacy of the Swiss Army. PMID- 27263153 TI - [Not Available]. PMID- 27263154 TI - [Not Available]. PMID- 27263155 TI - [Not Available]. PMID- 27263156 TI - [Not Available]. PMID- 27263157 TI - [Not Available]. PMID- 27263158 TI - [Not Available]. PMID- 27263160 TI - [Not Available]. PMID- 27263159 TI - [Not Available]. PMID- 27263161 TI - The Electronic Health Record--Making it Work for Us and Our Patients. PMID- 27263162 TI - Reflections: A CJD Diary. PMID- 27263163 TI - Total Ankle Arthroplasty Using the Agility Stemmed Talar Revisional Component: Three to Eight Year Follow-Up. AB - BACKGROUND: Ankle fusion has been the traditional treatment of choice for failed total ankle arthroplasties or arthritic conditions that preclude the use of primary implants. A custom stemmed agility talar component was designed to be used in these conditions. METHODS: The first 30 cases by a single surgeon were reviewed at two intervals. The study was a retrospective chart review with data including ankle diagnosis, deformity, bone loss and other factors that may have an impact on ankle arthroplasty. American Orthopedic Foot and Ankle Society (AOFAS) hindfoot clinical rating scale scores were recorded and this group of patients was reviewed post operatively at a mean of 19 months (6-52), and at a mean of 54 months (37-94). The design rational will be discussed, as well as a brief description of the surgical technique. RESULTS: Retention of the implant was 93 percent at a mean of 19 months and 88 percent at a mean of 54 months. AOFAS scores were improved from 55 to 71 at the latest review. Complications included two slow healing lateral incisions, one deep infection, one fractured stem, and one below knee amputation secondary to acute femoral artery occlusion. CONCLUSION: Our experience with this custom implant has allowed salvage of many complex and difficult talar sided problems that otherwise would have required a fusion. PMID- 27263164 TI - The Asfora Bullet Cage System Shows Comparable Fusion Rate Success Versus Control Cage in Posterior Lumbar Interbody Fusion in a Randomized Clinical Trial. AB - BACKGROUND: Low back pain and degeneration of the intervertebral disc are an integrated malady that affects millions of Americans. Cage devices used in association with posterior lumbar interbody fusion (PLIF) have been shown to be an effective approach in the treatment of a number of lower spine disorders attributed to degenerative disc disease (DDD). OBJECTIVE: This study was undertaken as part of a U.S. Food and Drug Administration (FDA) Investigational Device Exemption (IDE) study and compares the effectiveness of the Asfora Bullet Cage System (ABCS) to successfully fuse vertebra at one or two levels between L2 and S1 in patients with DDD to an FDA approved comparison device, the Medtronic Sofamor Danek Inter Fix Threaded Fusion Device (MSDIFD). METHODS: A total of 257 randomized participants were implanted with either the ABCS device (n = 132) or the MSDIFD device (n = 125) through an open posterior approach using autogenous local bone graft without the use of pedicle screws. Patients were evaluated prior to surgery and at the 24 month (24-M) visit for fusion status, deep tendon reflex status, sensory function, motor function, straight leg raise status, pain, disability, and device safety. Radiological evaluation and statistical analysis were performed by independent professionals. RESULTS: Evaluation of device success was performed at 24-M visit. From the original group of 257 patients, 59 were lost to follow-up. Primary measures of success at the 24-M visit involved pain and function, fusion, neurological status, and device-related adverse events measures. Pain and function improved in both (MSDIFD: 75.7 percent; ABCS: 82.6 percent). Fusion success with all radiographic points at 24-M visits was 79.4 percent MSDIFD and 88.2 percent ABCS. Neurological improvement was seen in both (MSDIFD: 77.0 percent; ABCS: 87.8 percent). One device-related grade 1 adverse event was reported in the MSDIFD group. Disc height preservation was equivalent for single level fusions (MSDIFD: 16.1 percent; ABCS: 20.0 percent) and second level fusions (MSDIFD: 10.7 percent; ABCS: 14.3 percent). General health and well being improvement was the same (MSDIFD: 37.0 percent; ABCS: 40.0 percent). Subsequent fusion, up to 10 years, was equivalent (MSDIFD: 83.8 percent; ABCS: 91.2). Results for both devices were considered to be satisfactory, with a slight non-significant superiority for the ABCS. CONCLUSION: From the ABCS device FDA IDE sanctioned study and the review of the literature, we concluded that the Asfora Bullet Cage System is safe, effective and comparable to other interbody fusion devices which are used stand-alone or in conjunction with pedicle screws, rhBMP-2, or autogenous bone harvested from the iliac crest inserted through anterior, lateral or posterior approaches. PMID- 27263165 TI - Takotsubo Cardiomyopathy (Broken-Heart Syndrome): A Short Review. AB - Takotsubo cardiomyopathy, also called "broken heart" syndrome or apical ballooning syndrome, is a reversible cardiomyopathy characterized by left ventricular dysfunction and ballooning of the left ventricular apex on imaging during systole. It predominantly occurs in post-menopausal women and is commonly associated with emotional or physical stress. Patients commonly present with chest pain and electrocardiographic evidence of ST segment elevation or T-wave mimicking acute coronary syndrome, but with an absence of angiographic evidence of obstructive coronary disease. The exact cause is unknown, but potential contributors include catecholamine excess and sympathetic nervous system hyperactivity. There is no consensus on pharmacological treatment of takotsubo cardiomyopathy. Based on the suspected pathophysiology of the disease, adrenergic blockade using beta-blocker therapy is employed. Near complete resolution of left ventricular wall motion dyskinesis occurs in the majority of takotsubo cardiomyopathy patients within a month. Although the prognosis is generally favorable, there are reports of complications during the acute phase, including cardiogenic shock, pulmonary edema, ventricular tachycardia, apical thrombus formation, and death. This review article will briefly discuss the epidemiology, etiology, clinical features, diagnostic evaluation, and treatment of this condition. PMID- 27263166 TI - So You Want to be an Author: A Primer on Writing for Publication in the Medical Literature Part I: Manuscript Preparation. AB - Writing a manuscript on a topic in the medical sciences that gets accepted for publication is not always a guaranteed process. The goal of this article is to provide a description of some key points associated with preparing a manuscript. It has been written primarily for less experienced or aspiring authors, but it addresses points that are important for even well-established authors to consider. Although there may not be a direct path from scientific observation to published work, possessing the desire to publish and persevering throughout the process can ultimately lead to one's findings being both preserved in and contributing to the scientific literature. Although challenging, and at times frustrating, it is a rewarding endeavor. PMID- 27263167 TI - Stress Ulcer Prophylaxis: Who, When, and Why Stress Out About It? PMID- 27263168 TI - DAKOTACARE Update: Positioned for the Future, Focused on Partnership. PMID- 27263169 TI - Quality Focus: Nursing Home Composite Measure Score: A Tool for Improvement. PMID- 27263170 TI - Patient Education: Destroy Your Enemy with Hate? PMID- 27263171 TI - Black is the new Orange. PMID- 27263172 TI - AMA Task Force to Reduce Opioid Abuse. Patients with a substance use disorder need treatment--not stigma. PMID- 27263173 TI - Rising Suicide Rate Leads to Increased Focus on Education, Prevention. PMID- 27263174 TI - Physician Assistants Increase Care Access. PMID- 27263175 TI - A Clinical Review of Tick-Borne Diseases in Arkansas. AB - Tick-borne diseases are illnesses transmitted by ticks harboring wide variety of pathogens. Arkansas is reported as one of the states with a high incidence of tick-borne diseases. In Arkansas the four most frequently occurring tick-borne diseases are Rocky Mountain Spotted Fever (RMSF, also known as Spotted Fever Rickettsiosis), Ehrlichiosis, Tularemia and Anaplasmosis. Lyme disease, on the other hand, is not acquired in Arkansas and is only acquired by traveling to states where Lyme disease is endemic. The majority of tick-borne diseases are diagnosed based on a history of tick bite or exposure and the individual's clinical presentation. The recognition of specific symptoms requires prompt treatment to prevent long-term sequelae. Hence, knowledge of tick-borne diseases and preventive measures can help reduce the risks associated with the infection. PMID- 27263176 TI - Marshallese COFA Migrants in Arkansas. AB - Arkansas is home to one of the largest populations of Marshallese in the world. Marshallese communities suffer from a disproportionate incidence of chronic diseases, including obesity, cardiovascular disease, diabetes, and infectious diseases, such as Hansen's disease (leprosy), tuberculosis, and types of hepatitis. There are a number of structural, legal, economic, and social issues that must be addressed in order to reduce health disparities and increase access to health care for Marshallese living in Arkansas. PMID- 27263177 TI - Lead From Where You Are. PMID- 27263178 TI - Association Between Asthma Hospital Visits and Ozone Concentration in Maricopa County, Arizona (2007-2012). AB - The objective of this study was to evaluate the association of asthma hospital visits with ozone concentrations in Maricopa County, Arizona. We used time plots and distributed lag nonlinear models to achieve these objectives while accounting for some potential confounders including temperature and day of the week. A total of 90,381 asthma hospitalizations were retrieved from the dataset (daily median = 39, range: 8-122). Asthma hospitalizations were highest in 2008 (16,949), during the months of November through December, and lowest in 2011 (13,213), during the months of June through July. By contrast, the average daily ozone concentration ranged from 27.05 parts per billion (ppb) in 2012 to 30.15 ppb in 2008 and from 13.96 ppb in December to 40.58 ppb in May. The association between asthma hospitalizations (relative risk [RR/per 10 ppb increase of ozone]) start at 1.046 (95% confidence interval [1.029, 1.064] at lag 0) and gradually decrease over several days. Our findings suggest exposure to ozone is associated with increased RR of asthma hospital visits in Maricopa County lasting several days. This study used recently developed methods that are freely available and could be used to evaluate other health events that are measured over time. PMID- 27263179 TI - Associations Between Ultrafine Particles and Co-Pollutant Concentrations in the Tampa Bay Area. AB - Ultrafine particles (UFPs) are ubiquitous in urban air and have been recognized as a risk to human health. The aim of this study was to measure the relationships among ultrafine particles and other ambient air pollutants and meteorological factors in the Tampa Bay Area. This study measured continuous UFPs, black carbon, oxides of nitrogen (NO(x)), nitrogen dioxide (NO2), nitric oxide (NO), carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2), particulate matter having an aerodynamic diameter of 10 microns or less (PM10), relative humidity, wind speed, and ambient temperature during January to March 2014. Moreover, the study compared the relationship between UFPs and various co-pollutants daily, including during morning rush hour periods. This study found a moderate correlation among UFPs and black carbon, NO(x), NO2, and NO during hourly continuous measurements and rush hour periods, and a low level of correlation among UFPs and CO, O3, SO2, PM10, relative humidity, wind speed, and ambient temperature. This study indicates that co-pollutants should not be used as a surrogate to assess the human health risk from ultrafine particles exposure. PMID- 27263180 TI - Swine Worker Precautions During Suspected Outbreaks of Influenza in Swine. AB - To assess the behavior and precautions that swine workers take during suspected influenza outbreaks in swine, six commercial swine farms in the Midwest U.S. region were visited when influenza outbreaks were suspected in herds during the fall/winter of 2012-2013. Use of personal protective equipment (PPE) and type of task performed by swine workers were recorded based on farm representative reports. Between one to two workers were working on the day of each visit and spent approximately 25 minutes performing work-related tasks that placed them in close contact with the swine. The most common tasks reported were walking the aisles (27%), handling pigs (21%), and handling equipment (21%). The most common PPE were boots (100%), heavy rubber gloves (75%), and dedicated nondisposable clothing (74%). Use of N95 respirators was reported at three farms. Hand hygiene practices were common in most of the farms, but reportedly performed for only 20% to 25% of tasks. PMID- 27263181 TI - Update From the Council for the Model Aquatic Health Code (and Why You Should Join). PMID- 27263182 TI - Exploring Environmental Health Gaps in Native American Populations. PMID- 27263183 TI - Environmental Health Is a Contact Sport. PMID- 27263184 TI - Five decades and counting.... PMID- 27263185 TI - Look back in wonder. PMID- 27263186 TI - Dignity in childbirth is a human right. PMID- 27263187 TI - Newborn screening in the UK. PMID- 27263188 TI - Testing times. PMID- 27263189 TI - Helping hands. PMID- 27263190 TI - Less talk, more action. PMID- 27263191 TI - Healthier choices and portions for older children. PMID- 27263192 TI - The right to care. PMID- 27263193 TI - Teenage pregnancy: job done, or more to do? PMID- 27263194 TI - Will Marriage Disappear? PMID- 27263195 TI - JANET DAVISON ROWLEY. PMID- 27263196 TI - Technology's Promise to Elders. PMID- 27263197 TI - Exploring Motivations, Awareness of Side Effects, and Attitudes among Potential Egg Donors. AB - This research study surveyed prospective egg donors at orientation to (a) understand women's motivations to donate eggs, (b) assess awareness and knowledge of egg donation prior to entry into the egg donation program, and (c) explore attitudes toward egg donation. Ninety-two women completed the questionnaire at one fertility clinic located in the Midwest between August 2011 and August 2012. Descriptive and inferential statistics as well as textual analysis were used to analyze the data. Three themes emerged regarding participant motivations: (1) altruistic, (2) financial, and (3) desire to pass on genetic material. The majority of participants were unconcerned with potential physical and psychological side effects; however, differences emerged based on motherhood status and educational level. Although potential donors felt recipients should receive some information about the donor, they tended to value privacy regarding information giving to resultant offspring. This research study has implications for social work practice, policy, and future research. It is crucial that women receive adequate procedural and side effect information prior to engaging in egg donation. PMID- 27263198 TI - Childhood, Adolescent, and Teenage Obesity: Recommendations for Community Initiatives in Central Harlem. AB - Because ofpoverty, the high prevalence of obesity, and the lack of adequate supports, Central Harlem's children, adolescents, and teenagers are at risk for major physiological, psychological, and social issues. This article discusses the public health concerns related to this population, especially the prevalence of obesity. This article identifies the prevalence of illness and obesity in the inner city and stipulates the causes and consequences of obesity among children, adolescents, and teenagers. In addition, it reports on the appropriate community intervention, using a coalition and a community collaborative organization that serve as models to build support for Central Harlem. A proposal is offered for reducing obesity among youths in the community. The intervention outlines a logic model that identifies a multisystemic approach at the micro and macro level for community intervention and policy initiatives to advocate for fundamental change. Further research recommendations are described to reduce the prevalence of childhood, adolescent, and teenage obesity in urban communities. PMID- 27263200 TI - Challenges Faced by Social Workers as Members of Interprofessional Collaborative Health Care Teams. AB - Interprofessional collaboration is increasingly being seen as an important factor in the work of social workers. A focus group was conducted with Canadian social work educators, practitioners, and students to identify barriers and facilitators to collaboration from the perspective of social work. Participants identified six themes that can act as barriers and facilitators to collaboration: culture, self identity, role clarification, decision making, communication, and power dynamics. These findings carry important implications for interprofessional collaboration with social workers in health practice. PMID- 27263199 TI - A Population Health Approach to Clinical Social Work with Complex Patients in Primary Care. AB - Chronic diseases disproportionately occur among people from disadvantaged backgrounds. These backgrounds correlate with poor health in adulthood. Capacity for patients' to collaborate in their care tends to be lower than among other patients, leading to inefficient uses in medical services and higher risk of adverse events. In the course of this study, social workers engaged patients with increased inpatient and emergency department (ED) use and barriers to self management, and evaluated them for lifetime exposure to material disadvantage and violence. Intervention focused on creating a primary care team that improved patients' self-efficacy, increased locus of control, and improved capacity for engagement. Results include a 49 percent decrease in admissions and a 5 percent decrease in ED utilization with significant cost savings. Authors recommend further study to analyze social, clinical, and financial risk in a larger sample, which may yield information about a health care provider's most at-risk patients for early targeted intervention. PMID- 27263201 TI - Distal Stressors and Depression among Homeless Men. AB - Depression is a common problem among homeless men that may interfere with functional tasks, such as securing stable housing, obtaining employment, and accessing health services. Previous research on depression among homeless men has largely focused on current psychosocial resources, substance abuse, and past victimization. Guided by Ensel and Lin's life course stress process model, the authors examined whether distal stressors, including victimization and exposure to parent problems in childhood, contributed to men's depression above and beyond current (or proximal) stressors, such as substance abuse and health problems, and social resources. The sample consisted of 309 homeless men who had entered a federally funded emergency shelter. Using the Burns Depression Checklist, the authors found that one out of three men met the threshold for moderate to severe depression during the past week. The logistic regression showed that past exposure to parent problems was related to depression after accounting for current stressors and social resources (number of close adult relationships and whether their emotional support needs were met). Past victimization was not related to depression. To address men's depression, workers should concurrently provide services that meet men's basic needs (for example, housing) and address their relationship needs, including their need for emotional support. PMID- 27263202 TI - A Qualitative Study of Smoking Behaviors among Newly Released Justice-Involved Men and Women in New York City. AB - Long-term effects of cigarette smoking result in an estimated 443,000 deaths each year, including approximately 49,400 deaths due to exposure to secondhand smoke. Tobacco is a major risk factor for a variety of chronic health problems, including certain cancers and heart disease. In this article, authors present qualitative findings derived from individual interviews with men and women who were incarcerated in New York state and New York City. Participants were 60 racially and ethnically diverse men and women ages 21 through 60 (M = 46.42, SD = 6.88). Of the participants interviewed, 91.7 percent released from a smoke-free correctional facility resumed cigarette smoking and 8.3 percent remained abstinent. Daily consumption ranged from smoking four cigarettes to 60 cigarettes. The four themes that emerged from the study were (1) lifetime exposure to cigarette smoking influences smoking behavior; (2) cigarettes help relieve stress and are pleasurable; (3) there is a relationship between access, availability, and relapse; and (4) smoking cessation strategies are available. Negative influences from participants' families and peers, stressful housing situations, and mandated programs emerged from this study as key challenges to abstaining from smoking cigarettes. Involving family members and partners in smoking cessation interventions could influence newly released justice-involved men and women not to resume cigarette smoking and possibly maintain long-term abstinence. PMID- 27263204 TI - [Practice of the use of remote telemedical consultations in "experimental area of work"]. AB - The article presents experimental results of telehealth technology of "medical company--military hospital--central military hospital". Requirements for the equipment, which is used for telehealth consultations and software are specified. Throughout the test were practiced emergency consultations of "physician physician" interface, including the use of mobile video call and portable terminals of videoconference, remote diagnosis with the use of medical equipment and devices. Data transmission features and video definition are received. The authors determined main types of telecommunication equipment, which are supposed to prospective for the Armed Forces. Prospects of implementation of telecommunication technologies are shown. PMID- 27263203 TI - Care Transition Experiences of Older Veterans and Their Caregivers. AB - This study's main objective was to examine care transition experiences of older veterans and their caregivers. Fifty patients age 65 years and older, discharged from a Veterans Affairs Medical Center hospital, completed the Care Transitions Measure-15 survey three to four weeks postdischarge. Seven patients and six caregivers participated in semistructured interviews. Overall, the quality of care transitions was rated as good; however, some items were indicated as problematic for veterans. Themes that emerged included agreeableness, frustration with complex information, caregiver education, and the timing and methods of information delivery. These findings have implications for all clinical staff working with veterans, and particularly for social workers facilitating care transitions for veterans and their caregivers. PMID- 27263205 TI - [Importance of social tuberculosis prophylaxis for the Armed Forces in present conditions]. AB - Lately social prophylaxis of tuberculosis has taken on special significance in the Armed Forces of the Russian Federation. Thank to social measures of the modern military reform, such as reduction of conscription term, territorial principle of recruitment for the army, improvement of habitation, service and recreation conditions, improvement of quality and organization of a diet, improvement of quality of a uniform it succeeded in reducing tuberculosis morbidity in military servicemen from 2007 up to 2014 up to 65 percent. Nevertheless, the main ways of tuberculosis control in the army (military service prohibition for citizens with tuberculosis, early active case detection, prophylaxis in risk group, anti-epidemic measures in the army nidus of tuberculosis etc.) are still urgent. To increase an effectiveness of the work done it is necessary to specify procedure and period of preventive fluorography in military servicemen. PMID- 27263206 TI - [Modern problems and main ways of imorovement of disinfecting art in Armed Forces]. AB - The article states the reasons defining the high relevance and significance of disinfection measures in modern conditions, reports general and specific problems of ensuring disinfection during medical service day-to-day activities. The directions of development of chemical and technical disinfectants and methods for'their use on different objects and under various climatic conditions are determined. It was shown that the crucial condition for implementation of theoretical and practical ways of improving disinfection affairs is a comprehensive approach based on concerted efforts of all authorities of Russian Armed Forces Medical Services, research and sanitary-epidemiological institutions, as well as relevant chars of the Military Medical Academy in close cooperation with representatives of domestic industry. PMID- 27263208 TI - [Objective roentgenologic diagnostics of anterior cruciform ligamentous disruption in servicemen]. AB - The article is dedicated to the method of roentgenological diagnostics, developed at military traumatology and orthopaedics department of the S.M. Kirov Military medical academy, which allows objectively assessing degree of knee joint instability in consequence of anterior cruciform ligamentous disruption. PMID- 27263207 TI - [Possibilities of pharmacotherapy of diabetes acute complications when delivering urgent and emergency aid]. AB - The authors give a description of acute complications when delivering urgent and emergency pharmacotherapy. The authors examined normative legal basis, regulating urgent and emergency aid delivery at the army level of the medical service of the Armed Forces of the Russian Federation, and determine the list of medications. Comparative description of pharmacotherapy of acute complications of diabetes is given and determined its possibilities. PMID- 27263209 TI - [Acute cholangitis in interstenosis space accompanied by two-component unit of the main bile duct]. AB - Palliative treatment of obstructive jaundice with the help of biliary endoprosthesis due to the possible complication of post-intervention in the form of insolvency stent deformation or dislocation. The study features in the postoperative period of the main bile duct endoprosthesis about their two component unit, described the syndrome of the closed space of the bile ducts. On the basis of observation of 14 patients with the given anatomical feature of endoscopic, who were underwent stenting, was assessed frequency of the syndrome and possibilities of its prevention. Interstenosis space expansion of the main bile duct can be a reason for local cholangitis. For the prevention of cholangitis, it should be carried out a separate drainage of interstenosis space with the help of endoprosthesis or by proximal supra-stenotic extension of two or more stents. PMID- 27263210 TI - [Experience of using bacteriophages and bitsillin-5 to reduce the incidence of respiratory diseases of bacterial ethiology in military personnel]. AB - The authors defined epidemiological efficacy and safety of the use of bacteriophages(streptococcal, staphylococcal, piobakferiophage multipartial) and bitsillin-5 to reduce tonsillitis morbidityand other respiratory diseases with bacterial etiology in groups of servicemen during their formationagainst increase of seasonal morbidity. The results of the use of these preventive agents were evaluatedby a comparative analysis of this disease in experimental and control groups. In total 510 healthy conscriptswere involved into the study. The effectiveness of prophylactic use of bacteriophages and bitsillin-5, whichprovided a reduction in the incidence of respiratory infections of bacterial ethiology, tonsillitis, and otherrespiratory diseases is showed. Recommendations on the choice of drugsfor the prevention of these infections,methods and organization of their application in organized groups are given. PMID- 27263211 TI - [Conditions of professional activity of the staff of units and formations of special support and its medical and psychological support]. AB - In the field of special support of nuclear- and radiation-dangerous objects "human factor" is highlighted, which means that psychological status of crew is at the first place. The authors analysed conditions of professional activity, determined morbidity rates and psychologically important labour characteristics for military specialists working at nuclear- and radiation-dangerous objects. The staff working at these objects undergoes irradiation, hostility of inhabitation and high psychological pressure. The authors presented data on peculiarities of health status and morbidity rate among military servicemen of the given category: the frequency of digestive apparatus diseases, diseases of nervous and circulatory systems is higher than in auxiliary subunits of the same military units. The authors determined the main principles and structure of measures of medical and psychological support of professional activity of the staff of military units of special support. PMID- 27263212 TI - [Experience of surgical care administration to patients with closed abdominal trauma, serving on the ships of the Navy]. AB - The analysis of surgical care administration to personnel, serving on ships of the Navy of Russia and performing different tasks in off-shore maritime and ocean zones in 2012-2013 showed that there is a requirement to create seven additional ship groups of specialized medical care: on the Northern Fleet--2, on the Pacific Fleet--2, on the Baltic Fleet--1, on the Black Sea Fleet--1, on the Caspian Flotilla--1. There is also a reasonable requirement to include anaesthesiologist and nurse anaesthetist into these groups. PMID- 27263213 TI - [Peculiarities of chemico-toxicological analysis of biological material aimed to detection of narcotic and psychoactive substances misuse by servicemen]. AB - The authors give an approval of military personnel biosphere research, which is necessary for prevention and early detection of substance misuse among military personnel of the Armed Forces. The article provides documents, regulating procedure of the chemico-toxicological analysis of a biological material, and staging of early detection of substance misuse among conscripts and professional soldiers. The authors gave information about main current problems of this activity, revealed its disadvantages and detected prevention measures. PMID- 27263214 TI - [Use of chemical war gases at the Russian-German front during the First World War]. AB - The First World War was notable for the widespread use of machine military hardware and absolutely new type of weapon--chemical weapon. As a result of the first gas attack by chlorine undertaken by the German army against the Russian armies on May, 31st, 1915, heavy poisonings have received 9100 people, 6000 of them died. Chemical attack of Germany against Russia was limited by the use chemical gases of suffocating action: chlorine, bromine,phosgene and diphosgene. It is not known exactly, how many times Germany attacked Russian positions with use of chemical gases. On available data, in the First World War from application by German of the chemical weapon Russia has suffered more, than any other of the at war countries: from five hundred thousand poisoned have died nearby 66,000 people. In turn, having received in the order the chemical weapon of own manufacture, Russian army itself tried to attack in the German armies. It is authentically known only about several cases of application dy Russian of fighting poison gases, and in all cases of loss of germen were insignificant. PMID- 27263215 TI - [Navy medical academy (to the 75th anniversary of establishment)]. AB - The article is devoted to the history of the creation in 1940 of the Naval Medical Academy on the basis of the 3rd Leningrad Medical Institute and the Institute for sanitary-chemical protection of the People's Commissariat of the USSR. The structure of this institution included, faculties management staff of the medical service, medical and sanitation, Higher Naval Medical School, the Marine Research Institute Medical, higher courses for officers of the medical service, clinical naval hospital. During the period of its activity (1940-1956), the staff of the Naval Medical Academy made a great contribution to the naval medicine and practical public health. The merit of the Academy is not only a beautifully staged academic, medical, research process, but also in the creation of the spirit of the high sea camaraderie, accomplishment and pride for the work which its graduates have dedicated their lives. PMID- 27263216 TI - [Poverty and Sickness. The precarious lives of lower-class families in Wurzburg and Gottingen, 1800-1850]. AB - This contribution focuses on the medical practice of the policlinics in Wurzburg and Gottingen in the first half of the nineteenth century. In these institutions patients were treated free of charge by medical students and assistant physicians who, in turn, were able to gain further experience and develop their skills. The policlinics were therefore an important part of poor-healthcare in both these cities. The essay tries in particular to illustrate healthcare for poor patients against the background of their everyday lives and working environment. Based on the situation of individual poor patients, the concepts of 'sickness' and 'poverty' are discussed as mutually dependent determinants of the 'reality of life' among the urban lower classes. This contribution combines the evaluation of medical practice journals and patient histories with the analysis of source materials on urban poor relief and healthcare. It looks particularly at the children and elderly people who attended the policlinics. The encounters between physicians and poor patients documented in the sources not only provide valuable insights into historical patient behaviours, they also open up new perspectives of the physician-patient relationship during the nineteenth century transition from the 'sickbed-society' to hospital medicine. PMID- 27263217 TI - [The Hygienist Karl Roelcke, M.D. (1907-1982). Annotations to the family biography]. AB - Volker Roelcke, the well-known historian of medicine, wrote a biographical sketch on his father's role in National Socialism. Karl Roelcke (1907-1982) was an important hygienist at the University of Heidelberg and assistant to Ernst Rodenwaldt (1878-1965). Attempts to discuss the Nazi issue with his father directly ended unsuccessfully in the 1970s. In his essay of 2014, Volker Roelcke portrayed his father as quite sophisticated, but did not mention all aspects of his work. The present essay therefore offers new insights into the person of Karl Roelcke which are not constrained by family interests. PMID- 27263218 TI - [Gender images in health education: a comparison between East and West Germany (1949-1990)]. AB - This essay takes a closer look at the shared traditions as well as separate developments in health education in both German states, based on the circulated gender images. Health education is a rewarding field of investigation because its materials not only convey information on the prevention of sickness or the cultivation of healthy lifestyles; they also--implicitly or explicitly--carry social key messages such as ideas regarding femininities and masculinities or the tasks and functions allocated to women and men within and outside the family. The fact, for instance, that women in East Germany were expected to be part of the labour force as early as the 1950 s, whereas their Western counterparts were expected to stay at home and look after the family, had an effect on health education. The question as to the normative images of femininity and masculinity is therefore at the centre of our inquiry. The sources used are health education publications and popular health magazines from both Germanies. Based on the parameters 'Home and Family', 'Work and Performance', 'Attractiveness and Outer Appearance', the ideas of femininity and masculinity, as portrayed in the health propaganda in East and West, are presented and compared. Analysis of these parameters shows that the gender images, while they coincided in some respects, also evolved in different ways in others, or that entirely different intentions were concealed behind the promotion of similar principles. Many of the guiding images discussed show how the two German states perceived each other. While there were attempts at dissociating from the other state entirely, there were also developments that seem to indicate that they referred to one another to a certain extent. PMID- 27263219 TI - [Protestant clergymen among Hahnemann's clientele. Patient histories in letters]. AB - As part of the research project, developments in the history of science and in the regional and ecclesiastic history of the late feudal petty state of Kothen Anhalt have been assessed and numerous documents of the Nagel and Muhlenbein family histories examined that place the transcribed patient letters of the two Protestant clergymen within the context of the Hahnemann Archives. These findings complement and extend previous insights into Hahnemann's Kothen clientele, especially when it comes to the structure and milieu of the local clerical elite. Inspired by the interpretive methods of sequential textual analysis, form and content of the letters of the two clergymen and their relatives were also investigated as methodically structured lines of communication. The body of sources published here presents--embedded in the body-image (of sickness and health) prevalent at the time--the medical cultures of educated patients as well as the increasingly professionalized medical practices of Samuel Hahnemann in a flourishing urban doctor's surgery. The correspondence between the pastors Albert Wilhelm Gotthilf Nagel (1796-1835) and August Carl Ludwig Georg Muhlenbein (1797 1866), presented here in a standard edition, has been investigated at Fulda University as part of the project 'Homoopathisches Medicinieren zwischen alltaglicher Lebensfuhrung und professioneller Praxis' ('Homeopathic medicine between everyday use and professional practice'). Of the altogether 78 transcribed documents, 53 are letters written by either of the two pastors, 16 are patient journals by Samuel Hahnemann, 9 letters by the pastors' wives and Muhlenbein's mother. The two series of letters, originally composed between 1831 and 1833 in old German cursive script, can now be used as sources for research into the history of homeopathy. PMID- 27263220 TI - [The company Willmar Schwabe in the Nazi era]. AB - This essay follows the history of the Schwabe Company between 1933 and 1945 when it, like all other companies at the time, had to subject to the state-enforced conformity ('Gleichschaltung'). While Willmar Schwabe II (1878-1935), the company's second director, kept clear of Nazi politics, both of his sons, who succeeded him at an early age, became members of the Nazi party: Willmar III (1907-1983) probably from initial conviction and Wolfgang (1912-2000), who joined in 1937, more likely for opportunistic reasons. The two lay journals published by Schwabe--the Leipziger Populare Zeitschrift fur Homoopathie and the Biochemische Monatsblatter--embraced the Nazi ideology more thoroughly than the general homeopathic journal Allgemeine Homoopathische Zeitung, including above all contributions on racial hygiene. Our research has revealed that Schwabe only employed foreign workers from 1942 on, that their number was much lower, at 0.9 per cent in 1942 and 3.6 per cent in 1944, than that of other pharmaceutical companies and that their pay hardly differed from that of German workers. The sales and profit figures investigated have shown that the company did not profit exceptionally from the new Nazi health policies ('Neue Deutsche Heilkunde'): while its sales and profits rose in the Nazi era due to the increased use of medication among the civil population during wartime, the drugs produced by Schwabe remained marginal also during the war, as is apparent also from its modest deliveries to the army. All in all one can conclude that the company offered neither resistance nor particular support to the Nazi ideology. PMID- 27263221 TI - [SERODIAGNOSIS OF THE MYCOBACTERIUM AVIUM COMPLEX BY USING IgA ANTIBODIES FOR THE GLYCOPEPTIDOLIPID CORE ANTIGEN]. AB - PURPOSE: The diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) can be challenging. A serodiagnosis enzyme immunoassay (EIA) kit, which detects the serum anti-glycopeptidolipid (GPL) core IgA antibody, has been commercialized recently; however, its clinical usefulness in the diagnosis of MAC-PD is still unclear. This study aimed to evaluate the availability of this kit and identify factors affecting testing accuracy. METHODS: We performed a retrospective study of 195 patients who were evaluated with an EIA kit at Nagasaki University Hospital between November 2012 and March 2014. RESULTS: 12 of 16 (75.0%) MAC patients have underlying diseases ; 8 of 16 (50%) had complications associated with respiratory diseases. There were no significant differences between the seropositive and seronegative background of patients with confirmed MAC-PD. Regarding the accuracy of serodiagnosis EIA kit, its sensitivity and specificity were 81.3% and 88.3% (with a cut-off value of 0.7 U/ml), respectively. Of false positive patients with bronchiectasis, 28.6 % demonstrated a good response to anti-MAC treatment, indicating that the sensitivity of the EIA kit might be higher than that of culture-based diagnosis because patients with clinically diagnosed MAC-PD were included in the false-positive population. CONCLUSIONS: In the current study, the serodiagnosis EIA kit demonstrated good sensitivity and specificity for the diagnosis of MAC-PD. Further clinical investigations are necessary to clarify the role of this kit in definitively diagnosing MAC infections. PMID- 27263222 TI - [THE CURRENT SITUATION OF FOREIGN TUBERCULOSIS PATIENTS AND THEIR CONCURRENT HIV INFECTION IN HOKKAIDO]. AB - BACKGROUND AND PURPOSE: According to recent news, patients with concurrent tuberculosis (TB) and human immunodeficiency virus (HIV) infection are increasingly common worldwide. This study aimed to investigate whether TB/HIV co infected patients are visiting Hokkaido. METHOD: We conducted a questionnaire survey regarding foreign patients infected with TB or TB/HIV who visited Hokkaido between January 2001 and September 2014. We mailed questionnaires to health centers, AIDS treatment care hospitals, and TB hospitals in Hokkaido prefecture. RESULTS: Seventy-one TB patients were of foreign nationality according to the answers obtained from health centers. Most of them were foreign students or occupational trainees between 20-30 years old. Approximately half these patients were from East Asia, and 7 patients were from Africa. As 21 % of the patients with TB who visited medical examination were over 1 month from disease onset, and the delay in visiting was recognized. The TB infection was mostly detected coincidentally during the physician visit. In the hospital survey, four TB patients with HIV were of foreign nationality. They were also of the age group from 20-30 years and hailed from sub-Saharan Africa. DISCUSSION: During immigration, medical examination by performing a chest radiograph is important. If the immigrant hails from an area where TB and HIV co-infection is common, it is necessary to confirm whether HIV infection is present. PMID- 27263223 TI - [CHANGES IN MAC ANTIBODY LEVELS BEFORE AND AFTER SURGERY AND AT THE TIME OF RELAPSE/RECURRENCE IN MAC LUNG DISEASE--Can MAC Antibodies Be an Indicator of Postoperative Relapse/Recurrence?]. AB - BACKGROUND: Patients receiving surgical treatment for Mycobacterium avium complex (MAC), lung disease should be followed up with careful attention paid to relapse/recurrence, but there is some debate regarding the findings based on which relapse/recurrence should be diagnosed. PURPOSE AND METHODS: We hypothesized that we might be able to use anti-GPL core IgA antibodies (MAC antibodies), which have been attracting attention as a factor that may support diagnosis of MAC lung disease, to diagnose postoperative relapse/recurrence. Therefore, we compared the levels of these antibodies before and at the time of relapse/recurrence, and also compared antibody titers before and after surgery. RESULT: MAC antibody titers were elevated by an average of about 50% at the time of relapse/recurrence compared to those before relapse/recurrence for 6 patients. In contrast, MAC antibody titers were about 30% lower after surgery compared to those before surgery for 37 patients. CONCLUSION: It may be possible to use MAC antibodies as an indicator of postoperative relapse/recurrence for MAC lung disease. PMID- 27263224 TI - [USE OF QuantiFERON(r) TB-GOLD IN-TUBE IN A CONTACT INVESTIGATION TO DETERMINE THE ONSET OF TUBERCULOSIS WITH OR WITHOUT LATENT TUBERCULOSIS INFECTION TREATMENT]. AB - PURPOSE: QuantiFERON(r) TB-Gold In-Tube (3G) testing was performed on tuberculosis-positive index cases and their contacts. The purpose of this study was to evaluate the relationship between 3G test results and the subsequent development of tuberculosis, and to identify effective strategies to prevent the onset of tuberculosis. METHODS: Index cases and their contacts were subjected to 3G testing in a contact investigation in Osaka City in 2011-2012. For index cases, sputum smears were tested, and the infecting organism was identified. For the contacts, the following information was collected: age, results of 3G testing, presence or absence of latent tuberculosis infection (LTBI) treatment, and onset of tuberculosis disease within 2 years of follow-up from the last contact with the index cases. RESULTS: (1) There were 830 index cases, including 774 subjects with pulmonary tuberculosis (93.3%) and 3 with laryngeal tuberculosis (0.4%). From sputum smear tests, 726 patients (87.5%) were determined to be 3G positive, and 83 (10.0%) were determined to be 3G negative. (2) In total, 2,644 contacts were subjected to 3G testing. Of these, 2,072 patients (78.4%) tested negative, 196 (7.4%) showed an equivocal result, and 375 (14.2%) tested positive. Their mean ages were 33.7, 38.0, and 38.8 years, respectively, showing significant differences in tuberculosis status according to age (P < 0.001). (3) Among the 2,072 3G-negative contacts, tuberculosis developed in 2 (0.1%) of 2063. None of these contacts was treated for LTBI. Among the 375 3G-positive contacts, tuberculosis developed in 36 (36.0%) of 100 subjects that were not LTBI treated, while tuberculosis developed in 3 (1.1 %) of 275 subjects that were LTBI treated. A significant difference in the incidence of tuberculosis between treated and untreated 3G-positive contacts was observed (P < 0.001). DISCUSSION: Tuberculosis developed in a high proportion of 3G-positive contacts that were not LTBI treated, suggesting the need for preventive management of 3G positive contacts. PMID- 27263225 TI - [COMPARISON OF QuantiFERON(r) TB GOLD TEST RESULTS BEFORE AND AFTER ENDOTOXIN CONTAMINATION]. AB - PURPOSE: In response to a case of endotoxin contamination of tubes used in QuantiFERON(r) TB Gold (QFT-3G) testing in Japan in 2013, the effect of this contamination on QFT-3G test results was investigated. METHODS: We analyzed QFT 3G results from 4,258 participants in a tuberculosis contact investigation in Yamagata, Japan from September 2010 to April 2015. Of these, 2,488 samples were collected before the endotoxin contamination, while 1,770 samples were collected after the contamination. RESULTS: Negative control values in the group tested after the contamination were significantly lower than those in the group tested before the contamination (P < 0.0005). The proportion of positive controls that exceeded the calculated limit (10IU/ml) in the group tested after the contamination (87.8%) was lower than that in the group tested before the contamination (96.8%; P < 0.0005). The proportion of intermediate results in the group tested after the contamination (3.2%) was markedly lower than that in the group tested before the contamination (6.6%). DISCUSSION: Differences in QFT-3G test results were found to be related to a difference in blood collection before or after endotoxin contamination of blood collection tubes. Values resulting from QFT-3G testing were lower in blood samples that were collected after the contamination relative to those collected before the contamination. PMID- 27263226 TI - [A CASE OF PULMONARY MYCOBACTERIUM ABSCESSUS INFECTION THAT DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY FOR MYASTHENIA GRAVIS WITH RECURRENT THYMOMA]. AB - A 58-year-old man developed cough, sputum, and low-grade fever during immunosuppressive treatment with corticosteroids and cyclosporine for myasthenia gravis with recurrent thymoma. Since chest CT revealed diffuse nodular opacities in both lung fields, he was referred to our department. Mycobacterium abscessus was repeatedly cultured from his sputum, and he was diagnosed with pulmonary M. abscessus infection. Although both chest radiological findings and clinical symptoms were mild, he required treatment with immunosuppressive agents and systemic anesthesia for resection of the recurrent thymoma. Based on complications and according to the patient's preference, oral treatment with clarithromycin 600 mg/day, levofloxacin 500 mg/day, and faropenem 600 mg/day was initiated on an outpatient basis. Following these treatments, his chest CT findings and clinical symptoms subsided, and the thymoma was successfully resected. Our experience with the present case suggests a possible treatment strategy for M. abscessus infection in immunocompromised and complicated cases. PMID- 27263227 TI - [A CASE OF MILIARY TUBERCULOSIS ORIGINATED FROM CUTANEOUS INFECTION]. AB - An 86-year-old woman with severe dementia had been treated with oral prednisolone at 2 mg/day for autoimmune bullous dermatosis for several years. One year ago, she referred to our hospital due to an ulcerative skin lesion over the right tibial tuberosity. The lesion was treated by an iodine-containing ointment, but did not heal. Subsequently, a new skin lesion appeared in the right popliteal fossa. One month ago, the patient had increased sputum production that was accompanied by fever, anorexia, and dyspnea; consequently, she visited our department. Chest computed tomography revealed diffuse micronodules with ground glass attenuation. Acid-fast bacteria staining of the sputum was positive and the polymerase chain reaction detected Mycobacterium tuberculosis. In addition, the bacilli were also found in the skin lesions of the right limb. Therefore, a diagnosis of cutaneous, and miliary tuberculosis was made. Although the anti tuberculous combination chemotherapy consisting of isoniazid, rifampicin, and ethambutol was immediately initiated, her condition did not improve. She died on day 19 of hospitalization. Drug susceptibility testing revealed no resistance to all the three drugs; hence, it was concluded that the time-delay in diagnosis of cutaneous tuberculosis lead to the progression to miliary tuberculosis and subsequent death. PMID- 27263228 TI - [TUBERCULOUS CONSTRICTIVE PERICARDITIS DETECTED ON POSITRON EMISSION TOMOGRAPHY]. AB - A 72-year-old man presented with fever, dyspnea, and weight loss. He was referred to our hospital for further examination of the cause of the pleural effusions. Chest computed tomography showed pleural effusions, a pericardial effusion, and enlarged lymph nodes in the carina tracheae. We administered treatment for heart failure and conducted analyses for a malignant tumor. The pericardial effusion improved, but the pericardium was thickened. Positron emission tomography computed tomography (PET-CT) showed fluorine-18 deoxyglucose accumulation at the superior fovea of the right clavicle, carina tracheae, superior mediastinum lymph nodes, and a thickened pericardium. Because these findings did not suggest malignancy, we assumed this was a tuberculous lesion. Echocardiography confirmed this finding as constrictive pericarditis; therefore, pericardiolysis was performed. Pathological examination showed features of caseous necrosis and granulomatous changes. Hence, the patient was diagnosed with tuberculous constrictive pericarditis. PET-CT serves as a useful tool for the diagnosis of tuberculous pericarditis. PMID- 27263229 TI - [PECULIARITY OF NATIONAL TUBERCULOSIS PROGRAM, JAPAN--Public-Private Mix from the Very Beginning, and Provision of X-ray Apparatus in Most General Practitioner's Clinics]. AB - Modern National Tuberculosis Program (NTP) of Japan started in 1951 when Tuberculosis (TB) Control Law was legislated, and 3 major components were health examination by tuberculin skin test (TST) and miniature X-ray, BCG vaccination and extensive use of modern TB treatment. As to the treatment program, Japan introduced Public-Private Mix (PPM) from the very beginning, and major reasons why PPM was adopted are (1) TB was then highly prevalent (Table 1), (2) TB sanatoria where many specialists are working are located in remote inconvenient places due to stigma against TB, (3) health centers (HCs) in Japan are working exclusively on prophylactic activities, and minor exceptions are treatment of sexually transmitted diseases and artificial pneumothorax for TB cases, however, as it covers on the average 100,000 population, access is not so easy in rural area, (4) Out-patients clinics mainly operated by general practitioners (GPs) are located throughout Japan, and the access is easy. Methods of TB treatment was developing rapidly in early 1950s, however, in 1952, as shown in Table 2, artificial pneumothorax and peritoneum were still used in many cases, and to fix the dosage of refill air, fluoroscopy was needed. Hence, GPs treating TB under TB Control Law had to be equipped with X-ray apparatus. To maintain the quality of TB treatment, "Criteria for TB treatment" was provided and revised taking into consideration the progress in TB treatment. If applied methods of treatment fit with the above criteria, public support is made for the cost of TB treatment. To discuss the applied treatment, TB Advisory Committee was set in each HC, composing of 5 members, director of HC, 2 TB specialists and 2 doctors recommended by the local medical association. In 1953, the first TB prevalence survey using stratified random sampling method was carried out, and the prevalence of TB requiring treatment was estimated at 3.4%, and only 21% of found cases knew their own disease, and more than half of all TB were found above 30 years of age. Based on these results, mass screening was expanded to cover whole population in 1955, and since 1957, cost of mass screening and BCG vaccination was covered 100% by public fund. Unified TB registration system covering whole Japan was introduced in 1961, and in the same year, national government subsidy for the hospitalization of infectious TB cases was raised from 50% to 80%. Hence, Japan succeeded to organize PPM system in TB care, and with 10% annual decline of TB, in 1975, Japan moved into the TB middle prevalence country. PMID- 27263230 TI - [M1 AND M2 MACROPHAGE POPULATIONS: THOSE INDUCED AND ACTIVATED BY MYCOBACTERIAL INFECTIONS]. AB - In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of. certain types of suppressor macrophage populations. During the course of infections due to pathogenic mycobacteria, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This review describes the immunological properties of M1- and M2-type macrophages generated in hosts with certain microbial infections including mycobacteriosis and those generated in tumor bearing animals. Particularly, this paper highlights the immunological and molecular biological characteristics of M1 and M2 macrophage populations, which are induced by mycobacterial infections PMID- 27263231 TI - [TUBERCULOSIS ANNUAL REPORT 2014--(1) Summary of Statistics on Tuberculosis Notification and Foreign-born Tuberculosis Patients]. AB - This brief is the first of a series of documents based on the Tuberculosis Annual Report 2014. It includes a summary of tuberculosis (TB) statistics, including data on foreign-born TB patients notified and registered in Japan in 2014. For the first time, the number of newly notified cases (all forms of TB) fell below 20,000. In 2014, a total of 19,615 patients were notified, a rate of 15.4 per 100,000 population The number of sputum-smear positive pulmonary. TB patients notified was 7,651, a rate of 6.0 per 100,000 population. The number of patients with latent TB infections increased slightly from 7,147 in 2013 to 7,562 in 2014. The proportion of miliary TB cases has constantly increased over the past 10 years, especially among women aged 80 years and older. The number of foreign-born TB patients continued to increase from 1,064 in 2013 to 1,101 in 2014. In 2014, new foreign-born TB patients aged 20-29 years accounted for 44.1% of all new TB patients in that age group. Among foreign-born TB patients, half were from the Philippines (26.5%) and China (23.5%). However, the number of patients from Vietnam and Nepal is increasing. Among foreign-born TB patients, 28% were regular employees, 26% were students, and 20% were unemployed. The changing trend in the nationality of foreign students entering Japan may at least partially explain the differences in TB burden among foreign-born patients, by country of birth. As we expect to see the proportion of foreign-born TB patients continue to rise, more tailored case identification and treatment support activities are needed. PMID- 27263232 TI - The Workplace Environment for African-American Faculty Employed in Predominately White Institutions. AB - Diversity in academia requires attention, especially with the expected increase in minority populations in the United States (American Association of Colleges of Nursing, (AACN) 2014). Despite theoretical papers that suggest that several challenges are encountered by minority faculty employed in predominately White institutions, a dearth of research on this topic has been published. The purpose of this literature review was to analyze the published research that addressed the workplace environment of African-American faculty employed in predominately White institutions. In utilizing the keywords in various combinations, 236 articles were retrieved through multiple databases. After applying inclusion and exclusion criteria, 15 studies were reviewed with only three related to nursing. Two themes were extracted from the review: 1) the cultural climate of the workplace environment and, 2) underrepresentation of African-American faculty. It is apparent from this review that additional research is needed to understand the experiences of this group of faculty to target effective recruitment and retention strategies. PMID- 27263233 TI - Multicultural Differences in Women's Expectations of Birth. AB - This review surveyed qualitative and quantitative studies to explore the expectations around birth that are held by women from different cultures. These studies are grouped according to expectations of personal control expectations of support from partner/others/family; expectations of carel behavior from providers such as nurses, doctors, and/or midwives; expectations about the health of the baby; and expectations about pain in childbirth. Discussed are the findings and the role that Western culture in medicine, power and privilege are noted in providing care to these women. PMID- 27263234 TI - Health, Healing, and Well-Being According to the New Testament. AB - The New Testament is regarded as the authoritative spiritual guidance for all practicing Christians. The relationship between religion and health continues to exert a significant role in an individual's, health, behavior, and lifestyle. This study aims at establishing a link between the Scriptural and early theological tradition of the body, from Jesus Christ to the early church, with an eye toward identifying themes that can help promote health and well-being among Christian communities today. PMID- 27263235 TI - Fluid technologies: The Bush Pump, the LifeStraw and microworlds of humanitarian design. AB - Over the past decade, many ingenious, small-scale gadgets have appeared in response to problems of disaster and extreme poverty. Focusing on the LifeStraw, a water filtration device invented by the company Vestergaard Frandsen, I situate this wave of humanitarian design relative to Marianne de Laet and Annemarie Mol's classic article on the Zimbabwe Bush Pump. The LifeStraw shares the Bush Pump's principle of technical minimalism, as well as its ethical desire to improve the lives of communities. Unlike the pump, however, the straw defines itself through rather than against market logic, accepting the premise that one can 'do well while doing good'. Moreover, it does not share the assumed framework of de Laet and Mol's Zimbabwean socio-technical landscape: a postcolonial state happily en route to national self-definition. Nonetheless, it clearly embodies moral affect, if in the idiom of humanitarian concern rather than development. My aim is to open up three interrelated lines of inquiry for discussion. First, I consider aspects of a postcolonial condition at the micro-level of immediate needs, including assumptions about nation-state politics and markets. Second, I emphasize science and technology in the form of infrastructure, the material frontline of norms. Third, I return reflexively to love, and the complicated allure of engagement in academic work. PMID- 27263236 TI - Survivors and scientists: Hiroshima, Fukushima, and the Radiation Effects Research Foundation, 1975-2014. AB - In this article, I reflect on the Radiation Effects Research Foundation and its ongoing studies of long-term radiation risk. Originally called the Atomic Bomb Casualty Commission (1947-1975), the Radiation Effects Research Foundation has carried out epidemiological research tracking the biomedical effects of radiation at Hiroshima and Nagasaki for almost 70 years. Radiation Effects Research Foundation scientists also played a key role in the assessment of populations exposed at Chernobyl and are now embarking on studies of workers at the Fukushima Daiichi Nuclear Power Plant. I examine the role of estimating dosimetry in post disaster epidemiology, highlight how national identity and citizenship have mattered in radiation risk networks, and track how participants interpreted the relationships between nuclear weapons and nuclear energy. Industrial interests in Japan and the United States sought to draw a sharp line between the risks of nuclear war and the risks of nuclear power, but the work of the Radiation Effects Research Foundation (which became the basis of worker protection standards for the industry) and the activism of atomic bomb survivors have drawn these two nuclear domains together. This is so particularly in the wake of the Fukushima disaster, Japan's 'third atomic bombing'. The Radiation Effects Research Foundation is therefore a critical node in a complex global network of scientific institutions that adjudicate radiation risk and proclaim when it is present and when absent. Its history, I suggest, can illuminate some properties of modern disasters and the many sciences that engage with them. PMID- 27263237 TI - Keeping gay and bisexual men safe: The arena of HIV prevention science and praxis. AB - Abstract In this article, I draw from an ongoing ethnographic study of HIV prevention for gay, bisexual, and 'men who have sex with men' to develop an institutional analysis of HIV behavioral intervention science and praxis. I approach this analysis through the lens of the social worlds framework, focusing on the institutional arena in which HIV behavioral interventions are devised and executed. Toward this end, I focus on two fundamental points of contention that lie at the heart of the prevention enterprise and put its social organization in high relief: (1) conceptions of health and lifestyle practices and (2) attributions of expertise. These core contentions reveal less the steady advance of normal science than an arena of actors ensconced in boundary work and jurisdictional struggles over how to engineer behavior change and reduce the scale of the HIV epidemic. Their resolution, I argue, has occurred in a historically contingent process determined by the political economy of the US HIV prevention arena and the differential structural location of its social worlds. PMID- 27263238 TI - From subjects to relations: Bioethics and the articulation of postcolonial politics in the Cambodia Pre-Exposure Prophylaxis trial. AB - Controversies about global clinical trials, particularly HIV trials, tend to be framed in terms of ethics. In this article, I explore debates about ethics in the Cambodia Pre-Exposure Prophylaxis trial, which was designed to test the safety and efficacy of tenofovir as a prevention for HIV infection. Bringing together studies of public participation in science with studies of bioethics, I show how activists around the Cambodian Pre-Exposure Prophylaxis trial circulated and provoked debates about standards of research ethics, as opposed to research methodology. This postcolonial bioethics was configured through the circulation of and debate about ethics guidelines, and historically and culturally specific relations of vulnerability and responsibility between foreigners and Cambodians and between Cambodian leaders and Cambodian subjects. I argue that this shift in the object of ethical concern, from the experimental human subject to the relation between subjects and researchers, illustrates how a postcolonial field of articulation reformulates classical bioethics. PMID- 27263239 TI - Beyond and between academia and business: How Austrian biotechnology researchers describe high-tech startup companies as spaces of knowledge production. AB - Research and innovation policy has invested considerable effort in creating new institutional spaces at the interface of academia and business. High-tech startups founded by academic entrepreneurs have been central to these policy imaginaries. These companies offer researchers new possibilities beyond and between academia and larger industry. However, the field of science and technology studies has thus far shown only limited interest in understanding these companies as spaces of knowledge production. This article analyses how researchers working in small and medium-sized biotechnology companies in Vienna, Austria, describe the cultural characteristics of knowledge production in this particular institutional space. It traces how they relate these characteristics to other institutional spaces they have experienced in their research biographies, such as in academia or larger corporations. It shows that the reasons why researchers decide to work in biotechnology companies and how they organize their work are deeply influenced by their perception of deficiencies in the conditions for epistemic work in contemporary academia and, to a lesser degree, in industry. PMID- 27263240 TI - The value of practice: A critique of interactional expertise. AB - Collins and Evans have proposed a 'normative theory of expertise' as a way to solve the 'problem of demarcation' in public debates involving technical matters. Their argument is that all citizens have the right to participate in the 'political' phases of such debates, while only three types of experts should have a voice in the 'technical' phases. In this article, Collins and Evans' typology of expertise--in particular, the idea of 'interactional expertise'--is the focus of a detailed empirical, methodological and philosophical analysis. As a result, we reaffirm the difference between practitioners and non-practitioners, contesting the four central claims about interactional expertise--namely, that (1) the idea of interactional expertise has been proven empirically, (2) it is possible to develop interactional expertise through 'linguistic socialization alone', (3) the idea of interactional expertise supports the 'the minimal embodiment thesis' that the individual human body or, more broadly, 'embodiment' is not as relevant as linguistic socialization for acquiring a language and (4) interactional experts have the same linguistic fluency, understanding and judgemental abilities of practitioners within discursive settings. Instead, we argue, individuals' abilities and understandings vary according to the 'type of immersion' they have experienced within a given practice and whether they bring with them another 'perspective'. Acknowledging these differences helps with demarcation but does not solve the 'problem of demarcation'. Every experience is perspectival and cannot handle, alone, the intertwined and complex issues found in public debates involving technical matters. The challenge, then, concerns the ways to mediate interactions between actors with distinct perspectives, experiences and abilities. PMID- 27263241 TI - A thousand words is worth a picture. AB - In this response to Ribeiro and Lima's paper on interactional expertise, we argue that, by not incorporating the insights of constructivist social science, their analysis goes backwards rather than advancing the debate. We show that much of the evidence they present does not lead to the conclusions they draw. We also critically examine the idea of physical contiguity, which forms a central part of Ribeiro and Lima's position. We show that its meaning is ambiguous. We conclude by suggesting that more research on the nature and influence of physical contiguity would be interesting in its own right but that it would not bear on the notion of interactional expertise. PMID- 27263242 TI - Home Sweet Home. PMID- 27263244 TI - An Introduction to the Medical Services of the Delaware Department of Correction. PMID- 27263243 TI - Opioid Exposed Mothers and Infants in Delaware: Clinical and Legal Considerations. AB - Drug use is on the rise in Delaware, as demonstrated by the continued increase in infants born with neonatal abstinence syndrome. Thoughtful, evidence-based, and coordinated approaches are necessary to impact this problem. There is solid evidence that mothers and infants who remain together have improved outcomes. Professional medical and nursing societies are unanimous in support of non punitive approaches to care. Medical professionals, legislators, and society in general would benefit from ongoing education on the addiction disease process in order to best care for the increasing number of mother/baby dyads with neonatal abstinence syndrome. PMID- 27263245 TI - Revenue Cycle Management Allows Your Staff to Concentrate on Clinical Issues. PMID- 27263246 TI - SNEAKING AROUND THE CONSTITUTION: PRETEXTUAL "HEALTH" LAWS AND THE FUTURE OF ROE V. WADE. PMID- 27263247 TI - THE PREGNANCY PENALTY. AB - Punishing pregnant women increasingly serves as a litmus test in political discourse, inviting more than a metaphor about state sanctioned violence targeted at women. In 2016, candidates for the United States presidency threatened to defund Planned Parenthood if elected and a leading candidate promised he would "punish" pregnant women who seek abortions. Other presidential candidates urged that even victims of rape and incest should be forced to carry their pregnancies to term, imposing yet another penalty or strike against sexually violated women and girls. Local legislatures and governors show equal contempt for and desire to penalize women in their states. In Utah, Gov. Gary Herbert took up the call to use a "very strong stick" in policing reproduction by signing into law the Criminal Homicide and Abortion Revisions Act, which applies only to pregnant women. The law seeks to punish pregnant women who "knowingly" commit acts that might result in miscarriages. In 2011, Texas Rep. Doug Miller authored and introduced a bill in his state legislature that would make it a felony to ingest any controlled substance during pregnancy. Wisconsin's legislature passed a law that forces pregnant women to receive vaginal probes as a pre-condition to receiving an abortion. To obtain an abortion without undergoing the vaginal probe is a punishable violation of law. Some women's groups compare vaginal ultrasound laws such as that in Wisconsin to state sanctioned rape with a rod. Other legislative efforts include establishing personhood in embryos and fetuses. Many of the laws seeking to punish pregnant women and regulate their pregnancies introduce criminal sanctions into gestational conduct, broadly criminalizing any behavior that could harm fetal health. All of these laws selectively target pregnant women. PMID- 27263248 TI - BORROWING FROM DORMANT COMMERCE CLAUSE DOCTRINE IN ANALYZING ABORTION CLINIC REGULATIONS. PMID- 27263249 TI - HOBBY LOBBY, BIRTH CONTROL, AND OUR ONGOING CULTURAL WARS: PLEASURE AND DESIRE IN THE CROSSFIRES. PMID- 27263250 TI - GENETIC ESSENTIALISM IN FAMILY LAW. PMID- 27263251 TI - THE "UBERIZATION" OF HEALTHCARE: THE FORTHCOMING LEGAL STORM OVER MOBILE HEALTH TECHNOLOGY'S IMPACT ON THE MEDICAL PROFESSION. PMID- 27263253 TI - MENTALLY ILL EMPLOYEES IN THE WORKPLACE: DOES THE ADA AMENDMENTS ACT PROVIDE ADEQUATE PROTECTION? PMID- 27263252 TI - IMPROVING THE EMERGENCY MEDICAL SERVICES SYSTEM'S RESPONSE TO DOMESTIC VIOLENCE. PMID- 27263255 TI - AMERICA NEEDS THE TREAT ACT: EXPANDING ACCESS TO EFFECTIVE MEDICATION FOR TREATING ADDICTION. PMID- 27263256 TI - FIRST Do No HARM: PROTECTING PATIENTS THROUGH IMMUNIZING HEALTH CARE WORKERS. PMID- 27263254 TI - TANTAMOUNT TO FRAUD?: EXPLORING NON-DISCLOSURE OF GENETIC INFORMATION IN LIFE INSURANCE APPLICATIONS AS GROUNDS FOR POLICY RESCISSION. AB - Many genetic counselors recommend that individuals secure desired insurance policies, such as life insurance, prior to undergoing predictive genetic testing. It has been argued, however, that this practice is "tantamount to fraud" and that failure to disclose genetic test results, or conspiring to secure a policy before testing, opens an individual up to legal recourse. This debate traps affected individuals in a Catch-22. If they apply for life insurance and disclose a genetic test result, they may be denied. If they apply without disclosing the information, they may have committed fraud. The consequences of life insurance fraud are significant: If fraud is found on an application, a life insurer can rescind the policy, in some cases even after the individual has passed away. Such a rescission could leave family members or beneficiaries without the benefits of the life insurance policy payment after the individual's death and place them in in economic difficulty. Although it is clear that lying in response to a direct question about genetic testing would be tantamount to fraud, few, if any, life insurance applications currently include broad questions about genetic testing. This paper investigates whether non-disclosure of unasked for genetic information constitutes fraud and explores varying types of insurance questions that could conceivably be interpreted as seeking genetic information. Life insurance applicants generally have no duty to disclose unasked for information, including genetic information, on an application. However, given the complexities of genetic information, individuals may be exposed to fraud and rescission of their life insurance policy despite honest attempts to truthfully and completely answer all application questions. PMID- 27263257 TI - THE CONSTITUTIONALITY OF SOLITARY CONFINEMENT: INSIGHTS FROM MASLOW'S HIERARCHY OF NEEDS. PMID- 27263258 TI - HUMAN TRAFFICKING: HOW A JOINT TASK FORCE BETWEEN HEALTH CARE PROVIDERS AND LAW ENFORCEMENT CAN ASSIST WITH IDENTIFYING VICTIMS AND PROSECUTING TRAFFICKERS. PMID- 27263259 TI - A Coupled Mathematical Model of Cell Migration, Vessel Cooption and Tumour Microenvironment during the Initiation of Micrometastases. AB - We propose a coupled mathematical model for the detailed quantitative analyses of initial microtumour and micrometastases formation by including cancer cell migration, host vessel cooption and changes in microenvironment. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. Migration probability of a migrating cell is assumed to be influenced by local chemical microenvironment. Pre-existing vessel cooption and remodelling are introduced according to the local haemodynamical microenvironment, such as interstitial pressure and vessel wall permeability. After the tumour cells and tumour vessels distribution are updated, the chemical substances are coupled calculated with the haemodynamical environment. The simulation results clearly reproduce the tumour cells migrate and proliferate along the pre-existing vessels at the very early stage of growth, which are consistent with many published experimental observations. In addition, the model demonstrates the interactions of tumour cells with the pre-existing vessels, which are believed to be essential for initial adhesion, proliferation, invasion, and micrometastases establishment. Quantitative analysis of tumour expansion in longitudinal and transverse directions shows that the cooption and migration along host vessels will be inhibited once angiogenesis phase occurs. The influences of the ability of cell migration and the inclusion of vessel cooption on the formation of micrometastases are discussed. PMID- 27263260 TI - Enhanced External Counterpulsation Treatment May Intervene The Advanced Atherosclerotic Plaque Progression by Inducing The Variations of Mechanical Factors: A 3D FSI Study Based on in vivo Animal Experiment. AB - Growing evidences suggest that long-term enhanced external counter-pulsation (EECP) treatment can inhibit the initiation of atherosclerotic lesion by improving the hemodynamic environment in aortas. However, whether this kind procedure will intervene the progression of advanced atherosclerotic plaque remains elusive and causes great concern in its clinical application presently. In the current paper, a pilot study combining animal experiment and numerical simulation was conducted to investigate the acute mechanical stress variations during EECP intervention, and then to assess the possible chronic effects. An experimentally induced hypercholesterolemic porcine model was developed and the basic hemodynamic measurement was performed in vivo before and during EECP treatment. Meanwhile, A 3D fluid-structure interaction (FSI) model of blood vessel with symmetric local stenosis was developed for the numerical calculation of some important mechanical factors. The results show that EECP augmented 12.21% of the plaque wall stress (PWS), 57.72% of the time average wall shear stress (AWSS) and 43.67% of the non-dimensional wall shear stress gradient (WSSGnd) at throat site of the stenosis. We suggest that long-term EECP treatment may intervene the advanced plaque progression by inducing the significant variations of some important mechanical factors, but its proper effects will need a further research combined follow-up observation in clinic. PMID- 27263261 TI - Design of Orthopedic Plates and Its Modification Based on Feature. AB - To quickly construct the orthopedic plates and to conveniently edit it, a novel method for designing the plates is put forward based on feature idea and parameterization. Firstly, attached to the existing or repaired bone model, the region of interest (ROI) is selected as the abutted surface of orthopedic plate, and the ROI is reconstructed to form a CAD surface. Secondly, the CAD surface is to be defined as a surface feature (SF) and then some semantic parameters are configured for it. Lastly, the plate body is constructed through thickening, and some higher parameters are defined for it so as to produce a volumetric feature (VF). In the above process, there exist two main problems: one is parameterization of the abutted surface, and the other is construction of the outer surface. Besides, the mapping relationship has to be built between surface feature parameters and volumetric feature parameters. This method supports the modification of high-level parameters, consequently promoting the quality and efficiency of orthopedic plate design. PMID- 27263263 TI - STOPPING DECEPTIVE HEALTH CLAIMS: THE NEED FOR A PRIVATE RIGHT OF ACTION UNDER FEDERAL LAW. AB - This Article offers a thorough analysis of an important public health issue, namely how to confront the growing problem of deceptive claims regarding foods and dietary supplements, including increasingly prevalent but unverifiable claims. The authors call for the creation of a limited private right of action under the Federal Trade Commission (FTC) Act for deceptive health-related claims for these products. The proposal responds to the growing market for these products and the inadequacy of current laws and enforcement actions to prevent such claims. In crafting the limited private right of action, the authors attempt to enhance consumer protection without undermining federal agency primacy in enforcement. The Article ends with an appendix setting forth proposed language for a statutory amendment to the FTC Act incorporating the authors' proposal. PMID- 27263264 TI - MANDATING DISCLOSURE OF CONSCIENCE-BASED LIMITATIONS ON MEDICAL PRACTICE. AB - Stakeholders in law, medicine, and religion are unable to reach consensus about how best to address conflicts between healthcare providers' conscientious objections to treatment and patients' rights to access medical care. Conscience laws that protect objecting providers and institutions from liability are criticized as too broad by patient advocates and as too narrow by defenders of religious freedom. This Article posits that some of the tension between these stakeholders could be mitigated by statutory recognition of a duty on the part of healthcare institutions or providers to disclose conscientiously motivated limitations on practice. While this solution would not guarantee a patient's access to treatment, referral, or information from any given provider, it would prevent some of the more egregious cases of denial of treatment--those where patients are not made aware that a legal and clinically defensible treatment option is excluded from a provider's or institution's scope of practice and so have no opportunity to seek care elsewhere. PMID- 27263262 TI - BETWEEN A ROCK AND A HARD PLACE: CAN PHYSICIANS PRESCRIBE OPIOIDS TO TREAT PAIN ADEQUATELY WHILE AVOIDING LEGAL SANCTION? AB - Prescription opioids are an important tool for physicians in treating pain but also carry significant risks of harm when prescribed inappropriately or misused by patients or others. Recent increases in opioid-related morbidity and mortality has reignited scrutiny of prescribing practices by law enforcement, regulatory agencies, and state medical boards. At the same time, the predominant 4D model of misprescribers is outdated and insufficient; it groups physician misprescribers as dated, duped, disabled, or dishonest. The weaknesses and inaccuracies of the 4D model are explored, along with the serious consequences of its application. This Article calls for development of an evidence base in this area and suggests an alternate model of misprescribers, the 3C model, which more accurately characterizes misprescribers as careless, corrupt, or compromised by impairment. PMID- 27263265 TI - BARTERING FOR A COMPATIBLE KIDNEY USING YOUR INCOMPATIBLE, LIVE KIDNEY DONOR: LEGAL AND ETHICAL ISSUES RELATED TO KIDNEY CHAINS. AB - Kidney chains are a recent and novel method of increasing the number of available kidneys for transplantation and have the potential to save thousands of lives. However, because they are novel, kidney chains do not fit neatly within existing legal and ethicalframeworks, raising potential barriers to their full implementation. Kidney chains are an extension of paired kidney donation, which began in the United States in 2000. Paired kidney donations allow kidney patients with willing, but incompatible, donors to swap donors to increase the number of donor/recipient pairs and consequently, the number of transplants. More recently, transplant centers have been using non-simultaneous, extended, altruistic donor ("NEAD") kidney chains--which consist of a sequence of donations by incompatible donors--to further expand the number of donations. This Article fully explains paired kidney donation and kidney chains and focuses on whether NEAD chains are more coercive than traditional kidney donation to a family member or close friend and whether NEAD chains violate the National Organ Transplant Act's prohibition on the transfer of organs for valuable consideration. PMID- 27263266 TI - DRIVE-BY-DOCTORING: CONTRACTUAL ISSUES AND REGULATORY SOLUTIONS TO INCREASE PATIENT PROTECTION FROM SURPRISE MEDICAL BILLS. PMID- 27263267 TI - QUIETING SPEECH: ESTABLISHING A BUFFER ZONE AROUND REPRODUCTIVE FREEDOM. PMID- 27263268 TI - Increasing Recognition of "Risk of Harm" as an Injury Sufficient to Warrant Standing in Class Action Medical Data Breach Cases--Walker v. Boston Medical Center Corp. PMID- 27263269 TI - [Regulatory Framework for Approval of PET Drug in Korea: A Survey Report]. AB - OBJECTIVES: To identify regulatory framework for approval of PET drugs in Korea. METHOD: Interview and literature survey. RESULTS: In Korea Good Manufacturing Practice (GMP) regulation specific to radiopharmaceuticals, including PET (Positron Emission Tomography) drugs, under the Pharmaceutical Affairs Act was issued in August 2014, to be enforced on July 1, 2015, and its guidance was issued in December 2014. The new facilities to be established after July 1 of 2015 have to be compatible with this new regulation and already established facilities have two years grace period until June 30 of 2017. During this period, the regulatory authority will inspect all of the production sites which hold or submit approvals of radiopharmaceuticals. As of September 2015 in Korea, there are 7 commercial companies and 15 hospitals and institutes, which have approvals of PET drugs mainly FDG, and these companies and/or hospitals can supply PET drugs outside institutions. In this article we introduce the Korean regulations of development and approval of radiopharmaceuticals. CONCLUSION: The Korean regulatory authorization policy for radiopharmaceuticals are to some extent similar to the policy which the U.S. regulators set as the new regulations of PET drug. It is expected that the situations of production sites in Korea are to be improved through actual discussions among regulators and PET community through the process of actual inspection. PMID- 27263270 TI - [The Development of a Normal Database of Elderly People for Use with the Statistical Analysis Software Easy Z-score Imaging System with 99mTc-ECD SPECT]. AB - We created a new normal database of elderly individuals (Tsukuba-NDB) for easy Z score Imaging System (eZIS), a statistical imaging analysis software, comprised of 44 healthy individuals aged 75 to 89 years. The Tsukuba-NDB was compared with a conventional NDB (Musashi-NDB) using Statistical Parametric Mapping (SPM8), eZIS analysis, mean images, standard deviation (SD) images, SD values, specific volume of interest analysis (SVA). Furthermore, the association of the mean cerebral blood flow (mCBF) with various clinical indicators was statistically analyzed. A group comparison using SPM8 indicated that the t-value of the Tsukuba NDB was lower in the frontoparietal region but tended to be higher in the bilateral temporal lobes and the base of the brain than that of the Musashi-NDB. The results of eZIS analysis by Musashi-NDB in 48 subjects indicated the presence of mild decreases in cerebral blood flow in the bilateral frontoparietal lobes of 9 subjects, precuneus and posterior cingulate gyrus of 5 subjects, lingual gyrus of 4 subjects, and near the left frontal gyrus, temporal lobe, superior temporal gyrus, and lenticular nucleus of 12 subjects. The mean images showed that there were no visual differences between both NDBs. The SD images intensities and SD values were lower in Tsukuba-NDB. Clinical case comparison and visual evaluation demonstrated that the sites of decrease in blood flow were more clearly indicated by the Tsukuba-NDB. Furthermore, mCBF was 40.87 +/- 0.52 ml/100 g/min (mean +/- SE), and tended to decrease with age. The tendency was stronger in male subjects than female subjects. Among various clinical indicators, the platelet count was statistically significantly correlated with CBF. In conclusion, our results suggest that Tsukuba-NDB, which is incorporated into a statistical imaging analysis software, eZIS, is sensitive to changes in cerebral blood flow caused by Cranial nerve disease, dementia and cerebrovascular accidents, and can provide precise diagnosis of these brain diseases in the rapidly aging Japanese population. PMID- 27263271 TI - [9th Symposium on Targeted Alpha Therapy]. PMID- 27263272 TI - [Diversity of proBDNF and mBDNF functions in the central nervous system]. AB - Brain-derived neurotrophic factor (BDNF) is one of the major protein regulators of diverse biological functions in the nervous system. It is synthesized as a precursor protein (proBDNF) that undergoes proteolytic cleavage in order to become a mature molecule. It was repeatedly shown that the proBDNF/ mBDNF ratio is determined by concomitant neuronal activity. A growing body of evidence argues that proBDNF has its own biological functions, oftentimes in opposition to functions of the mature molecule. Therefore, the balance of concentrations of proBDNF and mature neurotrophin is an important constituent of in any biological processes in nerve cells. Current review is dedicated to key aspects of proBDNF expression, its proteolysis to mBDNF, and its function in developing nervous system, long-term synaptic plasticity, memory consolidation and extinction and possible involvement in pathologies of nervous system. PMID- 27263273 TI - [An fMRI Study of the Brain Activation Related to Intensive Positive Emotions During Viweing Erotic Pictures in 49-74 Old Men]. AB - According to psychological research erotic images are evaluated in the context of positive emotions as the most intense, most associated with emotional arousal, among the variety of pleasant and unpleasant stimuli. However it is difficult to separate areas of the brain that are related to the general emotional process from the activity of the brain areas involved in neuronal representations of reward system. The purpose of this study was to determine differences in the brain activity using functional magnetic resonance imaging (fMRI) in male subjects in evaluating an intensity of pleasant images, including erotic, or unpleasant and neutral pictures. When comparing the condition with evaluation of the pleasant erotic images with conditions containing neutral or unpleasant stimuli, a significant activation was observed in the posterior cingulate cortex; the prefrontal cortex and the right globus pallidus. An increased activity of the right anterior central gyrus was observed in the conditions related to evaluation of pleasant and neutral stimuli. Thus, in the process of evaluating the intensity of emotional images of an erotic nature the active brain areas were related not only to neuronal representations of emotions, but also to motivations and control system of emotional arousal, which should be taken into account while using erotic pictures as intensive positive emotional stimuli. PMID- 27263274 TI - [Structure of Response and Dynamics of Preferred Orientation in Cat's V1 Neurons]. AB - Preferred orientation of V1 neurons was changed during the respons time course. In order to reveal mechanisms of such changes, spike trains of single neurons to flashed bars of different orientations were studied by means of principal component and frequency-domain analysis of the spike density functions. There was found out that: 1. contribution of each of the components was dependent on the stimulus orientation. 2. the principal components of V1 neurons responses contain different kinds of transient and sustained parts and rhythmic oscillations in the theta/alpha and beta-bands. 3. There was no correlation between transient parts as well as between rhythmic oscillations within the same frequency band in different components. Taken together, the data obtained allow us to suggest that during generation of response there is a shift of dominance of the components with different orientations which determines the dynamics of the preferred orientations of V1 neurons. PMID- 27263275 TI - [Delayed Copying of Unfamiliar Contour Shapes: Does Reaction Time Decrease with Growing Delay Reflect a Change in Internal Representation Of Fothcoming Movement?]. AB - Group of 24 adults has performed the delayed reproduction (copying) of unfamiliar contour shapes (trajectory templates). Templates were shown for 250 ms and the participants were asked to reproduce them upon detecting acoustical go signal (short click). Go signal was delayed relatively to the end of a visual template exposure by T = 0, 500, 1000, 2000 or 4000 ms. Block design of the experiment was used when delay T was held constant within a block consisted of 32 trials. We analyzed reaction time (RT), mean movement time (MT) along a single segment of trajectory, and the mean dwell time (DT) in the vertices of the template. It is shown that RT does not depend monotonically on the delay T showing a decrease at T <= 1000 ms and increase at T <= 2000 ms. The RT of T curve is well described by a simple additive model that includes a linearly growing and an exponentially decaying terms. The linear growth reflects the foreperiod effect, i.e., decreasing capacity to predict an exact moment of go signal with the growing delay T [Niemi, Naatanen, 1981; Meulenbroek, Van Galen, 1988]. We suggested that exponentially decaying term may be caused by the internal representation of a trajectory undergoing some transformation during retention in the working memory. PMID- 27263276 TI - [Kinematics of Stair Ascent in Children and Adolescents with Autism Spectrum Disorder]. AB - We analyzed kinematics of stair ascent and descent in autistic children and adolescents in comparison with age-matched healthy children and adolescents. Eight healthy adolescents, 6 autistic adolescents, 7 healthy children and 6 autistic children participated in the study. We found that autistic subjects of both groups showed significantly more fluctuations of hip joint angular velocity than age-matched control subjects while preparing for stair ascent. During preparation for stair descent these velocity fluctuations appeared mainly in autistic adolescents, moreover, autistic children exhibited less velocity fluctuations than children in control group while preparing for stair descent. The kinematics of the movement itself demonstrated significantly less hip abduction in both autistic children and adolescents than in age-matched controls during stair ascent, and less ankle joint plantar extension in autistic adolescents than in healthy adolescents during stair descent. We suppose that age related changes in kinematics of leg motion during stair ascent and descent in autistic patients indicate aggravated motor coordination in autistic adolescents as compared with both healthy adolescents and autistic children. PMID- 27263277 TI - [Wulst Activation in Pied Flycatcher Nestlings in Feeding Behavior Induced by Patterned Visual Stimulus]. AB - Immunohistochemical detection of c-Fos was used to study the transcriptional activation in two higher visual centers (Wulst area and Entopallium) of 12-day old pied flycatcher (Ficedula hypoleuca) during the realization of feeding behavior guided by patterned visual stimulus, simulating the species-specific one. Activation was compared in 4 groups of nestlings. Control group was not subjected to any experimental influence. In binocular, right-field (deprivation of the left eye) and left-filed (deprivation of the right eye) groups the vision feeding responses were provoked, reinforced and evaluated. It was shown that the visual afferentation from the right eye was more significant for the organization of early feeding behavior guided by a moving patterned visual stimulus as compared with the afferentation from the left eye. Feeding behavior induced activation of c-Fos expression only in neurons of the higher center of thalamofugal system--Wulst area. The comparison of transcriptional activation in different groups revealed the significant increase of c-Fos induction related with feeding behavior only in the left hemisphere and only in binocular and right field groups. PMID- 27263278 TI - [Does Impulsivity Affect a Long-term and Working Memory in rats?]. AB - In the present paper usingthe method of delay discounting three groups of animals were discovered: a) those that at choice between immediate weak and delayed strong rewards have chosen an immediate reinforcement (high impulsive rats); b) those that were able to inhibit its own behavior and get the delayed reinforcement (low impulsive rats); and c) the rats with both types of reactions. In the water maze the different groups of rats did find a hidden platform for different time, swum various distance and with different speed. The differences however were significant only at overall comparison (for all days and trials) of the above mentioned parameters of the water maze learning. ANOVAs Group x Days, Group x Trials, and Groups x Days x Trials interactions were insignificant. The data obtained indicate that the difference between groups was appeared evidently due to the difference in general motor activity, rather than difference in their cognitive abilities assessed by reference and working memory tasks. PMID- 27263279 TI - [Comparative Analysis of Behavior in The Open-field Test in Wild Grey Rats (Rattus norvegicus) and in Grey Rats Subjected to Prolonged Selection for Tame And Aggressive Behavior]. AB - The aim of this work is analysis of the open-field behavior in grey rats selected for the tame and aggressive behavior in comparison with the wild grey rats. Significant influences of the rat group factor on the 13 of 19 behavioral features studied in the open-field were found. This effect, in general, depends on existence of great differences between behaviors of the wild rats from the one hand and behaviors of the tame and aggressive rats from the other. The behaviors of the rats from the last two groups are practically identical. Multidimensional analysis confirms the distinct separation in coordinates of the two main components of the wild rat behavior from the behavior of both the tame and selectively bred aggressive rats. The first main component dimension corresponds to the grade of fear, which was significantly enhanced in the wild rats. So, in spite of the equality of behavioral aggressiveness of the wild rats and the rats selected for aggression with the glove test, the behavior of selected aggressive rats in the open-field is analogous to behavior of the rats selected for tameness. Comparison of behavioral features with the hormonal stress responsiveness allowed us to conclude that the aggressive behavior of the wild and se lected for aggression rats based on different motivational and neuroendocrine processes. PMID- 27263280 TI - [Thalamo-Cortical Mechanisms of Initiation, Maintenance and Termination of Spike wave Discharges at WAG/Rij rats]. AB - Generalized spike and wave discharges (SWDs) are generated within the cortico thalamo-cortical system, being an electroencephalographic sign of absence epilepsy. The current work aims to identify mechanisms of SWD initiation, maintenance and termination. Dynamics and directionality of mutual interactions between neocortex (occipital (OC) and frontal (FC) cortex) and thalamus (reticular (RTN) and ventral postero medial (VPM) thalamic nuclei) were investigated. SWD initiation process is revealed several seconds before seizure onset in interaction between all brain areas, except intrathalamic pair (RTN VPM). This process begins at different moments relatively to SWD onset. The interaction increase is observed earlier and most obviously when thalamus and OC drive FC. The maintenance process (the first few seconds of SWD) is accompanied with high level interaction inside thalamus and increase of driving from thalamus to occipital cortex. Thus interaction from thalamus and occipital cortex to frontal cortex and influence to VPM occur to be below baseline level. At the SWD offset thalamo-cortical interactions were found to return to baseline level quickly. PMID- 27263281 TI - [Method of Calculating the Distance Between the Classes of the Structural Components of the Forebrain Birds]. AB - The method of calculating the distance between the classes of the structural components of the brain of birds. Compared interclass distances of glia, neurons and neuroglial complexes in the forebrain hooded crow (Corvus cornix) (a bird with a highly rational activity) and common crossbill (Loxia curvirostra) (birds with a medium level of rational activity). PMID- 27263282 TI - You are a Leader! PMID- 27263283 TI - Legal Corner. PMID- 27263284 TI - [Effect of Progesterone-induced MicroRNA-152 on the Proliferation of Endometrial Epithelial Cells]. AB - OBJECTIVE: To determine the expression of microRNA-152 induced by progesterone and its effect on the proliferation of endometrial epithelial cells (EECs). METHODS: Cultured EECs, Ishikawa were divided into four groups: control group (C group), 10(-8) mol/L estrogen treated group (E group), 10(-6) mol/L progesterone group (P group) and estrogen plus progesterone treated group (E&P group). The expression of mature microRNA-152 (microRNA-152-3p) of was detected by qRT-PCR. The estrogen treated cells were transfected with mimic-microRNA-152-3p. The estrogen and progesterone treated cells were transfected with inhibitor-microRNA 152-3p. Cell proliferations were detected by CCK-8 assay. The target gene of microRNA-152-3p proteins was predicted using microRNA target databases and validated by Western blot. RESULTS: qRT-PCR showed no difference between C and E groups (P > 0.05) in the expression of microRNA-152-3p. P group had higher expressions of microRNA-152-3p than C group (P < 0.05). E&P group had higher expressions of microRNA-152-3p than C group and P group. MicroRNA target protein prediction suggested that CDC14A is one of direct target proteins of microRNA-152 3p. The results of CCK-8 assay showed that mimic-microRNA-152-3p transfection blocked proliferations of estrogen treated cells and lowered expressions of CDC14A in these cells; while inhibitor-microRNA-152-3p promotes proliferations of estrogen and progesterone treated cells and increased expressions of CDC14A in these cells. CONCLUSION: Progesterone may suppress proliferations of EECs through inducing expressions of microRNA-152-3p. CDC14A is probably one target protein of microRNA-152-3p for its action on EECs. PMID- 27263285 TI - [Effect of Resveratrol Preconditioning on Myocardial Dysfunction after Cardiac Arrest in Rats]. AB - OBJECTIVE: To investigate the protective effects and its potential mechanism of resveratrol preconditioning on rat cardiac arrest after return of spontaneous circulation (ROSC) with the study of hemodynamic parameters and nitrative stress in myocardium. METHODS: Cardiac arrest SPF SD rat model was established by transoesophageal cardiac alternating current stimulation. Intervention was implemented 15 min before cardiac arrest. Twenty four rats with ROSC after cardiac arrest were randomly assigned into five groups: vehicle, sham, resveratrol 2.3 mg/kg (A group), resveratrol 0.23 mg/kg (B group) and resveratrol 0.023 mg/kg (C group). Heart rate, mean arterial pressure, and left ventricular variables (+ dp/dtmax and - dp/dtmin) were recorded in 0.5 h, 1.0 h, 2.0 h, 3.0 h, and 4.0 h respectively. Rats were sacrificed at 4 h after ROSC, and hearts were removed for determining expression of inducible nitric oxide synthase (iNOS) protein, myocardial peroxynitrite, and nitrotyrosine. RESULTS: Global ROSC rate was 72.7% after the induction of cardiac arrest. Resveratrol preconditioning did not improve ROSC rate significantly. Heart rate and blood pressure declined at early phase of ROSC, then heart rate recovered to the baseline value, but blood pressure still declined progressively. There were no significant differences between resveratrol groups and vehicle group. Myocardial function worsened progressively even after ROSC. Resveratrol improved cardiac function significantly, especially in lower concentration groups. Myocardial iNOS expression, peroxynitrite, and nitrotyrosine content increased significantly after ROSC. Resveratrol decreased these products significantly, and lower concentration groups did better. CONCLUSION: Resveratrol preconditioning could improve cardiac dysfunction after ROSC, which may be associated with its inhibitory effect on nitrative stress. PMID- 27263286 TI - [The Experiment Study and Mechanism of Aspirin Enhances Cellular Sensitivity of Hepatocellular Carcinoma Cell Line to Arsenic Trioxide]. AB - OBJECTIVE: To explore whether aspirin could sensitize arsenic trioxide on human hepatocelluar carcinoma cell line and understanding the combination mechanisms underlying co-treatment. METHODS: Cell viability was detected by MTT assay, cell apoptosis rate and reactive oxygen species (ROS) level were measured by flow cytometry, and Western blot assay was used to estimated the protein expression of heme oxygenase-1 (HO-1) in total protein and NF-E2-related factor 2 (Nrf2) in nuclear protein. RESULTS: 10 MUmol/L arsenic trioxide can decreased the cell viability, while cell apoptosis rate, ROS level, HO-1 and Nrf2 protein expression was increased (P < 0.05). When compared with arsenic trioxide alone, co-treatment of arsenic trioxide with aspirin in different concentration (0, 0.1, 1.0, 2.5, 5.0 mmol/L) exhibited dual effects in intracellular ROS level, HO-1 and Nrf2 expression. Specifically, with the increasing of aspirin concentrations, the level of ROS induced by arsenic trioxide showed a rising trend after the first reduction, whereas, HO-1 and Nrf2 protein expression were decreased at first and then increased. CONCLUSION: Low concentration, less than 2.5 mmol/L, of aspirin may reduce the ROS accumulation through activating of Nrf2-HO-1 pathway, therefore decreasing the apoptotic cell death induced by arsenic trioxide. On the contrary, 5 mmol/L aspirin could increase the sensitivity of HepG2 to arsenic trioxide through enhancing the arsenic trioxide-induced apoptosis by ROS accumulation resulting in inhibiting the Nrf2-HO-1 pathway. PMID- 27263287 TI - [3D Collagen Hydrogel Culture of Rat Calvarial Osteoblasts]. AB - OBJECTIVE: To establish a collagen hydrogel three-dimensional culture model with rat calvarial osteoblasts (ROBs). METHODS: ROBs were obtained through enzyme digestion of segregated neonatal SD rat skull. The collagen hydrogel three dimensional culture model was established by mixing ROBs with different concentrations of type I rat tail collagen (collagen concentration of 1, 2, 3 mg/mL), DMEM medium and NaOH under adjusted PH and a temperature of 37 degrees C. Cell viability and activity were detected by FDA/PI staining and CCK-8 3 d after cell culture. The optimal culture method of 3D collagen hydrogel was identified. Cell distribution was observed using scanning electron microscopy and HE staining. RESULTS: ROBs collagen was formed firmly at 2 mg/mL, which had significantly higher levels of cell viability and activity than those at 1 mg/mL and 3 mg/mL. Scanning electron microscopy and HE staining showed that cells under the 2 mg/mL collagen culture system adhered with collagen tightly and distributed homogeneously. CONCLUSION: A collagen hydrogel 3D culture model was established successfully by mixing ROBs with collagen at 2 mg/mL. PMID- 27263288 TI - [Effects of Tetrandrine Prenatal Intervention on Alveolar Epithelial Cells Type I Differentiation in Rat Model of Nitrofen-induced Congenital Diaphragmatic Hernia]. AB - OBJECTIVE: To investigate the effects of Tetrandrine (TET) prenatal intervention on the differentiation of alveolar epithelial cells type I (AEC I) in rat model of Nitrofen-induced congenital diaphragmatic hernia (CDH). METHODS: Timed pregnant Sprague-Dawley rats were divided into three groups, namely control, CDH and TET group on day 9.5 of gestation. The rats in TET group and CDH group were given 125 mg of Nitrofen by gavage one time, while the rats in control group were given the same dose of seed fat. After that, the rats in TET group was given 30 mg/kg of TET by gavage once a day for three days from day 18.5 of gestation, while the rats in CDH and control group were given the same dose of normal saline. On day 21.5 of gestation, all fetuses were delivered by cesarean, the lungs of fetuses were histologically evaluated by microscope and electron microscope. The expressions of type I cell-specific protein (RT140) and thyroid transcription factor 1 (TTF1) in alveolar fluid content were analyzed by RT-PCR and immunohistochemistry staining. To detect the number of AEC I and AEC II of each group by transmission electron microscopy and calculate the percentage of AEC I and AEC II (I/II%). RESULTS: The microscope and electron microscope study found the lungs of fetuses in CDH group showed marked hypoplasia, in contrast to the improvement of hypoplasia in TET fetuses. The pulmonary alveolar area had significant difference statistically (P < 0.01) in each group, which present as control > TET > CDH. I/II% had significant difference statistically (P < 0.01) in each group, which present as control > TET > CDH. The expression level of TTF1 was up-regulated in both CDH and TET groups, and it was higher in CDH group (P < 0.01). The expression level of RT140 were down-regulated in CDH and TET groups, which was lower in CDH group (P < 0.01). CONCLUSION: The development of AEC I was interfered in CDH rat model, TET prenatal treatment could improve the lung development of CDH. PMID- 27263289 TI - [Expression of Type 3 Acid Sensitive Ion Channels in Bladder of OAB Rat Model]. AB - OBJECTIVE: To investigate the expression of type 3 acid-sensing ion channels (ASIC3) in bladder tissue of over active bladder (OAB) rat model. METHODS: Sixty adult female rats were randomly divided into control group (intraperitoneal injection of 0.9% sodium chloride), GAB group (intraperitoneal injection of cyclophosphamide) and the intervention group (OAB rats treated with ASIC3 inhibitor amiloride). The rats underwent urodynamic testing. The bladder tissues were collected for pathological examination, while the expressions of ASIC3 were measured by the methods of immunohistochemistry, RT-PCR and Western blot. RESULTS: Urodynamic study found that the rats in control group had no significant contraction instability in both storage and voiding stages. Compared with the control group, OAB group and intervention group showed instability of visible contraction in urine storage stage, with shorter micturition interval (P < 0.01) and increased frequency of urination (P < 0.01). Compared with the OAB group, the intervention group showed significantly prolonged micturition interval (P < 0.05) and reduced frequency of urination (P < 0.05). Pathologic examination showed rat bladder mucosal damage in both OAB group and intervention group. Immunohistochemistry found the expression of ASIC3 on bladder mucosa. RT-PCR and Western blot showed significantly higher expression of ASIC3 in OAB group (P < 0.01), but the expression of ASIC3 decreased in intervention group after adding ASIC3 inhibitor. CONCLUSION ASIC3 expresses mainly on bladder mucosa. The gene and protein expression of ASIC3 in rat bladder tissue of OAB rats is higher, which can be significantly decreased by ASIC inhibitor. The symptoms of OAB reduce after intervention, which demonstrates the increased expression of ASIC3 in bladder tissue is closely related to bladder detrusor. PMID- 27263291 TI - [Expressions and Clinical Significance of Autophagy-related Genes ATG2B, ATG4D, ATG9B in Breast Carcinoma]. AB - OBJECTIVE: To investigate the expressions and clinical significance of autophagy related gene 2B (ATG2B), autophagy-related gene 4D (ATG4D), autophagy-related gene 9B (ATG9B) in breast cancer cell lines and breast cancer. METHODS: Cancer Browser screening was applied to study the differential expressions of ATG2B, ATG4D, ATG9B genes in breast cancer. Quantitative Real-time PCR was used to measure the expressions of these three genes in human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435S and ZR-75-30) as well as 83 cases of breast cancer samples with paired normal breast tissues. The relationships between the expressions of these genes and clinicopathological characteristics were further analyzed. RESULTS: Cancer Browser screening found abnormal expressions of ATG2B, ATG4D, ATG9B in breast cancer (P = 0.015, P = 0.028, P = 0.040). All four breast cancer cell lines expressed ATG2B, ATG4D, ATG9B, and the expression of ATG2B, ATG9B was significantly lower than positive control (P < 0.001), but ATG4D expression was higher than positive control (P < 0.001). The expressions of ATG2B, ATG4D, ATG9B in breast cancer were all lower than those in the adjacent normal tissues (P < 0.001, P = 0.031, P < 0.001). Furthermore, the expression of ATG2B was correlated with ER (r = 0.949, P = 0.015), and the expression of ATG4D was related to age (r = -0.449, P = 0.005), the expression of ATG9B was correlated to lymph node metastasis and cytokeratin 5/6 status (r = 0.339, P = 0.043; r = 0.533, P = 0.043). CONCLUSION: ATG2B, ATG4D, ATG9B genes shows low expressions in breast cancer, which may become new molecular markers for the prognosis of breast cancer. PMID- 27263290 TI - [Expression of BMP2/Smad1/Runx2 Signal Pathway in Renal Artery of Rat with Vascular Calcification]. AB - OBJECTIVE: To investigate the activation and its role of bone morphogenetic protein 2 (BMP2)/Smad1/Runt-related transcription factor 2 (Runx2) signal pathway in renal artery of rat models with vascular calcification. METHODS: Twenty four male SD rats were randomly divided into control group and calcification group. Rat vascular calcification model was constructed by administration of vitamin D3 plus nicotine. Vascular calcification was confirmed by Von Kossa staining and calcium content was detected by calcium assay. Real time-PCR was applied to detect the expression of BMP2, Smad1, Runx2 mRNA, and immunohistochemistry was used to measure the protein levels of BMP2, Smad1, Runx2, alpha-smooth muscle actin (alpha-SMA). RESULTS: Von Kossa staining showed a large number of black granules deposited in renal artery. Calcium content in calcification group was significantly higher than that in normal group. Compared with the control group, the expressions of BMP2, Smad1 and Runx2 mRNA in renal artery were increased in calcification group. The protein levels of BMP2, Smad1 and Runx2 were higher while the expression of alpha-SMA was lower in calcification group than those in control group. The correlation analysis was found a positivie correlation between the calcium content and BMP2 mRNA (r = 0.655, P < 0.05), Smad1 mRNA (r = 0.735, P < 0.05), Runx2 mRNA (r = 0.734, P < 0.05). CONCLUSION: The expression of BMP2/Smad1/Runx2 signal pathway was strongly correlated with the severity of vascular calcification, which may be involved in the occurrence and development of vascular calcification. PMID- 27263292 TI - [Effect of Intron Orientation on the Expression of Transgene Imposed by MAR Expression Vector in Stably Recombinant CHO Cells]. AB - OBJECTIVE: To determine the effect of intron orientation on the transgene expression level imposed by matrix attachment region (MAR) expression vector. METHODS: The MAR of beta-globin was amplified by PCR, and then cloned into MAR expression vectors. An intron sequence was digested with restriction enzyme, ligated to the MAR expression vector in reverse orientation, and then transfected into Chinese hamster ovary (CHO) cells. The transfected stable cells were screened by G418. The level of chloramphenicol acetyltransferase (CAT) gene expression was analyzed by ELISA method. RESULTS: The transgene expression levels of CHO cells with the two expression vectors with a positive intron or without MAR were higher than that of CHO cells with an expression vector with reverse intron (P < 0.05). MAR did not improve transgene expression with reverse intron presence. CONCLUSION: Different orientation of intron can affect transgene expression in recombinant CHO cells. The transgene expression level can be increased using positive intron and MAR. PMID- 27263293 TI - [The Immunomodulatory and Anti-allergy Effects of Lactobacilli]. AB - OBJECTIVE: This study was conducted to evaluate the potent immunomodulatory effects of Lactobacilli and their possible anti-allergic effects. METHODS: Lactobacillus plantarum LP45 (LP45), Lactobacillus acidophilus La28 (La28), Lactobacillus acidophilus 6091 (6091), Lactobacillus rhamnosus GG (LGG) were orally administrated to male BALB/C mice, respectively for 28 d. The immune organ index, serum Th1 cytokines [interferon-gamma (IFN-gamma), interleukin-12 (IL-12)] and Th2 cytokines IL-6 of the tested mice were analyzed with ELISA after intervention. Furthermore, La28, 6901 were also orally fed to ovalbumin (OVA) sensitized male BALB/C. The serum total IgE of the tested mice was analyzed with ELISA after intervention. RESULTS: No statistical difference was found in immune organ index among the tested four strains. La28 significantly decreased serum IL 6 of the tested mice after 14 d and 28 d compared to those in control (P < 0.05). After 28 d, 6091 also significantly reduced serum IL-6 of the tested mice (P < 0.05). La28 significantly suppressed the increase of serum total IgE of the tested mice (P < 0.05). CONCLUSION: The present study indicates that the immunomodulatory effects of Lactobacilli might be strain-dependent. Among the tested strains of Lactobacilli, La28 and 6091 may have possibility to influence the Th2 immunity of host animal. La28 may also posse potent ability to alter IgE mediated allergy by the way to affect Th1/Th2 balance of host animal. PMID- 27263294 TI - [Prevention and Therapeutic Effects of Fuzheng Huayu Capsule on Liver Fibrosis and Expression of Connective Tissue Growth Factor in Rats]. AB - OBJECTIVE: To investigate the prevention and therapeutic effects of Fuzheng Huayu Capsule on liver fibrosis in rats and its possible mechanism by regulating the expression of connective tissue growth factor (CTGF). METHODS: Forty Wistar rats were randomly divided into five groups: the normal group, the preventive group (the preventive experimental group and the preventive control group) and the treatment group (the treatment experimental group and the treatment control group). All the rats, except those in the normal group, were given CCl4 by subcutaneous injection and alcohol by oral adminstration to establish the model of liver fibrosis; meanwhile the rats in normal group were given same amount of olive oil by subcutaneous injection and water by oral administration. The preventive experimental group and control group were treated with Fuzheng Huayu crude drug 0.46 g/kg body mass through stomach irrigation and saline respectively once a day for four weeks during the modeling process. The treatment experimental group and control group were treated with Fuzheng Huayu crude drug 0.46 g/kg body mass through stomach irrigation and saline respectively once a day for four weeks after the modeling process. Blood was collected for the examination of liver function and serum fibrosis marker. HE staining was used to examine the pathological changes in liver tissue. The expression of CTGF was detected by immunohistochemistry. RESULTS: Compared with the preventive experimental group, total bilirubin (TB), alanine aminotransferase (ALT) and hyaluronic acid (HA) in the preventive control group decreased significantly (P < 0.05). Compared with the treatment control group, ALT and laminin (LN) in the treatment experimental group decreased significantly (P < 0.01). Compared with the treatment comtrol group, the inflammation and hepatic fibrosis in the treatment experimental group alleviated significantly. The expression of CTGF in the treatment experimental group were significantly lower than that in the treatment control group (P < 0.05). CONCLUSION: Fuzheng Huayu Capsule showed the prevention and therapeutic effects on experimental liver fibrosis. Meanwhile, Fuzheng Huayu Capsule could inhibit the CTGF expression in liver tissue, which may be one of the molecular mechanisms of these effects. PMID- 27263295 TI - [Effect of Electro-acupuncture on the Expression of Slit2 and HSPGs in Rats with Focal Cerebral Infarction]. AB - OBJECTIVE: To determine the expression of Slit2 and heparan sulfate proteoglycans (HSPGs) in cortex of rats with focal cerebral infarction and the effect of acupuncture (EA) on the expression of Slit2 and HSPGs. METHODS: 40 male Sprague Dawley (SD) rats were equally randomized into four groups: Control group, model group, non-acupoint EA group, and EA group. Thread-tying method was used in the model group, non-acupoint EA group and EA group to clog arteries and then open up after 1.5 h. Morphology changes of tissues around the infarction area were observed 14 days later by Nissl staining. The expressions of Slit2 and HSPGs in the ischemic brain tissues were detected by indirect immunofluorescence staining (IF) and Western blot (WB). RESULTS: Modified neurologicalseverity scores (mNSS) showed zero in the control group, lower than the score of EA group. The EA group had lower mNSS score than the non-acupoint group. The highest mNSS score appeared in the model group. Paired comparisons showed statistical differences (P < 0.01). Nissl's staining showed that EA group had increased Nissl bodies in alignment; non-acupoint EA group had increased and disordered Nissl bodies; model group had decreased and disordered Nissl bodies with edema in the brain. IF and WB showed that non-acupoint EA group had higher levels of Slit2 and HSPGs than model group (P < 0.05); EA group had higher levels of Slit2 and HSPGs than non-acupoint EA group (P < 0.05); model group had higher levels of Slit2 and HSPGs than control group (P < 0.05). The results of Nissl' s staining, IF and WB were consistent. CONCLUSION: EA can enhance the expressions of Slit2 and HSPGs. This may be one of the mechanisms of EA promoting recovery of neural functions after cerebral infarction. PMID- 27263296 TI - [Effect of Electroacupunctrue on ERp57 in NAFLD Rats]. AB - OBJECTIVE: To investigate the effect of electroacupunctrue on ERp57 in non alcoholic fatty liver disease (NAFLD) rats, and study the therapeutic mechanism of electroacupunctrue in patients with NAFLD. METHODS: Sixty male SD rats were randomly divided into common diet group (n = 15) and high-fat diet group (n = 45). 5 weeks later, two rats from the two groups were executed and confirmed that the model was successful. Then 10 rats in common diet group were chosen as control group (Control), and 40 rats in high-fat diet group were randomly chosen and divided into diet group 1 (D1), diet group 2 (D2), electroacupuncture group 1 (EA) and electroacupuncture group 2 (EA2) (n = 10 each). D1 and EA1 were fed by high fat diet; D2 and EA2 were fed with common diet. In EA1 and EA2, filiform needle acupuncture was applied to ST36, SP6 and Liv3 and electroacupunctrue was applied to one-side of ST36, SP6 for 20 min once daily for 4 weeks. The rats in each group were weighed per-week. After the treatment the changes of blood lipid and liver functions of these rats were observed. ERp57 gene expression and protein expression were detected by RT-PCR and Western blot, and expression of ERp57 downstream SREBP-1c was detected. RESULTS: The body mass of D1 increased slowly and were lower than D2 and EA1 (P < 0.05); the body weights of EA2 increased rapidly and were higher than EA1 (P < 0.05), but without significant difference with D2 (P > 0.05). The contents of blood lipid, liver functions and the expression of ERp57 and SREBP-1c were significantly higher than those in Control, D2 and EA1 (P < 0.05). While compared to D2 and EA1 respectively, the index mentioned above in EA2 decreased more significantly (P < 0.05). CONCLUSION: Electroacupunctrue can decrease expression of ERp57 to improve endoplasmic reticulum stress (ERS) of rats with NAFLD and then decrease expression of SREBP 1c to regulate rat lipid, which could be one of mechanism to cure NAFLD. PMID- 27263297 TI - [Effects of Side-effect Attenuation Prescriptions on Cyclophosphamide-induced Myelosuppression in Mice]. AB - OBJECTIVE: To determine the effects of Side-effect Attenuation Prescriptions on the levels of white blood cells (WBC), hemoglobin (HGB) and platelet (PLT) in peripheral blood of mice influenced by cyclophosphamide (CTX). METHODS: Mice were randomly divided into 6 groups: normal control group, myelosuppression group induced by CTX (model group), recombinant human granulocyte colony stimulating factor (G-CSF) group, and Side-effect Attenuation Prescriptions group (experimental groups with high, middle, and low dosages). Marrow depressed models were established by injecting CTX intraperitoneally (40 mg/kg, once/d, 10 d) to the mice. High, middle, and low dosage experimental groups received 40 g/kg, 20 g/kg, and 10 g/kg Side-effect Attenuation Prescriptions once a day for two weeks, respectively. Mice in the G-CSF group were given G-CSF (50 MUg/kg) by hypodermic injection three days before blood sampling. Levels of WBC, HGB and PLT counts in peripheral bloods of the mice were detected at 7 d and 14 d after the marrow depressed models were established. RESULTS: The Side-effect Attenuation Prescriptions slowed down the decline of blood levels of WBC, HGB and PLT induced by CTX (P < 0.05), and accelerated the recovery of WBC and HGB levels compared with model group at 14 d (P < 0.05). CONCLUSION: The Side-effect Attenuation Prescriptions can accelerate recovery of WBC, HGB and PLT in peripheral bloods of mice. PMID- 27263298 TI - [Effect of Leflunomideon Inflammatory Factors and Immune Function in Rats with Chronic Glomerulonephritis]. AB - OBJECTIVE: To investigate the effect of leflunomide on the inflammatory factors and immune function of rats with chronic glomerulonephritis. METHODS: Thirty rats of chronic glomerular nephritis model were established by injecting cationic bovine serum albumin (C-BSA). Rats with successfully modeled were randomly divided into model group and observation group. Another 15 rats injected with physiological saline in the same way were chosen as the control group. Modeling after 2 weeks, rats in the observation group were given leflunomide meters suspension by gavage treatment with 5 mg/(kg x d). Rats in the control group and model group were given equal volume of saline. Rats were killed after continuous intragastric for 4 weeks. The levels of serum creatinine, blood urea nitrogen, serum total cholesterol, serum albumin and 24 h urine protein were recorded. mRNA and protein levels of peripheral blood tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were detected by RT-PCR and ELISA method. Peripheral blood T lymphocyte subsets were evaluated by flow cytometry (FCM). RESULTS: Compared with the control group, the levels of serum creatinine, blood urea nitrogen, serum total cholesterol, serum albumin and 24 h urine protein in model group and observation group were significantly increased (P < 0.05); Compared with the model group, these biochemical indexes in observation group decreased significantly (P < 0.05). Comparison with the control group, mRNA and protein levels of peripheral blood TNF-alpha and IL-6 in model group and observation group rats were significantly increased (P < 0.05). Compared with the model group, mRNA and protein levels of TNF-alpha and IL-6 were significantly decreased (P < 0.05). Compared with the control group, peripheral blood T lymphocyte subsets in the model group and observation group were imbalance, the difference was significant (P < 0.05). Compared with the model rats, T lymphocyte subsets in the observation group after treatment tended to be stable (P > 0.05). CONCLUSION: Leflunomide can significantly reduce the levels of biochemical indexes and inhibit the inflammatory reaction. The mechanism may be related to the regulation of immune function. PMID- 27263299 TI - [Expression of Serotonin Receptor and Transporter Related Genes of CD4+ T Lymphocytes in Patients with Asthma and Depression]. AB - OBJECTIVE: To explore the comorbidity mechanism of asthma and depression. METHODS: A self-developed questionnaire, which also contained Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ) and Hamilton Rating Scale for depression ( HRSD), was administered in 41 participants with asthma (AS), asthma and depression (AD), or none any of these conditions (health control, HC). Lung function and blood levels of eosnophils and IgE were also detected in those in the AS and AD groups. Blood CD4+ T cells were isolated in all of the participants to extract RNA for reverse transcription to cDNA. Real-time polymerase chain reaction (RT-PCR) was performed using cDNA as a template to detected the expression levels of HTR1A, HTR2A, HTR7, SLC6A4, and B2M genes. RESULTS: Participants with AS and AD had lower expression level of SLC6A4 than the healthy controls (P = 0.000). The expression level of HTR2A in participants with AS was lower than that in the healthy controls (P = 0.021) and marginally lower than that in participants with AD (P = 0.077). Participants with AD had lower AQLQ scores than participants with AS (P = 0.004). CONCLUSION: Asthma and depression is correlated at gene level. Decreased expression of SLC6A4 gene may be one of the possible comorbidity mechanisms of asthma and depression. PMID- 27263300 TI - [Association of Vitamin D Receptor Polymorphisms with Response to Antiviral Therapy in Patients with Chronic Hepatitis C]. AB - OBJECTIVE: To assess the influence of vitamin D receptor (VDR) gene Bsm I, Fok I, Taq I and Apa I polymorphisms on the response to antiviral therapy in patients with chronic hepatitis C (CHC). METHODS: There were total 124 patients with CHC treated with pegylated interferon plus ribavirin. VDR gene Bsm I, Fok I Taq I and Apa I polymorphisms were analyzed in 71 patients with sustained virological response (SVR) and 53 patients without SVR (non-SVR) by polymerase chain reaction MassARRAY (PCR-MassARRAY). RESULTS: The distributions of VDR genotype met Hardy Weinberg equilibrium (all P > 0.05). There were no significant differences in VDR Fok I, Taq I, Apa I allele and genotype frequencies between SVR and non-SVR patients (all P > 0.05). The Bsm I (GA) genotype was significant higher in the patients with SVR compared to those with non-SVR (Chi2 = 3.967, P = 0.046). Three SNPs at VDR gene (Bsm I, Taq I and Apa I) were in strong linkage disequilibrium. Linkage disequilibrium coefficient (D') between Bsm I and Taq I was 1.000 and the correlation coefficient (r2) was 0.741. D' between Bsm I and Apa I was 1.000 and r2 was 0.082. D' between Taq I and Apa I was 0.829 and r2 was 0.076. No relation existed between haplotypes and response to therapy (P > 0.05). CONCLUSION: Vitamin D receptor gene Bsm I polymorphism may be associated with the therapeutic response to antiviral therapy with pegylated interferon plus ribavirin in chronic hepatitis C patients. PMID- 27263301 TI - [Gene Mutation Spectrum Analysis of 170 Patients with Duchenne/Bayesian Muscular Dystrophy in Southwest of China]. AB - OBJECTIVE: To determine gene variations and genotype-phenotype correlations in Duchenne/Bayesian muscular mystrophy (DMD/BMD) patients, and the association between dystrophin gene polymorphisms and clinical phenotype. METHODS: Multiplex ligation-dependent probe amplification (MLPA) was adopted to detect dystrophin gene variations in 170 patients. Sanger sequencing was performed in 3 cases with decreased peaks in MLPA results. RESULTS: The MLPA detected 72.94% mutations in dystrophin gene, including 62.35% (106/170) deletions, 8.82% (15/170) duplications, and 1.76% (3/170) point mutations. 64 different types of mutations were found. 75.47% of deletions occurred in the range from exon 44 to 55. Most 5' breakpoints of exonic variations were located in 2 hotspots (major hotspot: intron 43-55; minor hotspot: intron 1-20), which is different from findings of other studies. Genotype-phenotype analysis showed that the severity of DMD/BMD was associated with frame shift mutation (r = 0.640, P < 0.001) but not with deletions or duplications. CONCLUSION: Deletions and duplications of exon compose the main type of dystrophin gene mutations. DMD/BMD is associated with frame shift mutation. PMID- 27263302 TI - [Equity of Health Resources Allocation in Minority Regions of Sichuan Province]. AB - OBJECTIVE: To determine equity of health resources allocation in minority regions of Sichuan province from 2009 to 2013. METHODS: Health resources distribution equity among populations and across geographic catchments were measured using coefficients of Inter-Individual differences and Individual-Mean differences. RESULTS: Health resources, especially human resources, in minority regions increased slowly over the years. Poorer allocation equity was found in nursing resources compared with doctors and hospital beds. Better distribution equity was found among populations than across geographic catchments. High levels of equity in resource distributions among populations and across geographic catchments were found in Aba. In Liangshan, more equitable distributions were found in doctors and hospital beds compared with nurses. The rest of minority regions had poor absolute allocation equity in doctors and hospital beds among populations. CONCLUSION: Appropriate allocation of health resources can promote health development. Health resources allocation in minority regions of Sichuan province is unreasonable. The government and relevant departments should take actions to optimize health resources allocations. PMID- 27263303 TI - [Dietary Fiber and Pubertal Development among Children and Adolescents--a Cross sectional Study in Chengdu, Sichuan]. AB - OBJECTIVE: To determine the association between intake of dietary fiber and pubertal development among children and adolescents in Chengdu. METHODS: A cross sectional survey was undertaken in 1 340 children and adolescents aged 9-15 years. Data about dietary intake were collected through 24-h dietary self-recall. Pubertal development was measured by trained investigators using Tanner criteria. Consumptions of total fiber and fiber from different sources were compared among the participants with different stages of pubertal development. RESULTS: Data from 1 328 children and adolescents were analyzed. Boys (n = 667) at a later stage of pubertal development consumed less total fiber and fruit fiber than those at an earlier stage (P < 0.05). Similarly, girls (n = 651) at a later stage of pubertal development consumed less fruit fiber than those at an earlier stage (P < 0.05). CONCLUSION: Dietary fiber intake, especially fruit fiber, is lower in children and adolescents with early commencement of puberty development. Further studies are needed to establish the relationship between dietary fiber and pubertal development. PMID- 27263304 TI - [Regional Differences and Determinants of Self-rated Health in Elderly]. AB - OBJECTIVE: To determine differences of self-rated health in elderly people across geographic regions of China, and to identify factors influencing self-rated health of elderly. METHODS: Ordered logistic modeling was performed using the China Health and Retirement Longitudinal Study (CHARLS) data in 2013. RESULTS: Elderly people resided in Eastern China had better self-rated health than their counterparts residing in Middle (partial regression coefficient 0.252, P < 0.01) and Western (partial regression coefficient 0.338, P < 0.001) China. Sex, residency, education, per capita consumption expenditure, smoking and drinking, social participation, chronic diseases, and life satisfaction were identified as associated with self-rated health of elderly. CONCLUSION: There are regional differences in self-rated health of elderly. Policy priorities should be given to Middle and Western China, with more health resources being allocated to those regions. Regional economic and educational inequalities need to be addressed. Healthy lifestyle should be promoted. PMID- 27263305 TI - [Three-dimensional Ultrasound of the Pelvic Floor in Early Postpartum after First Delivery]. AB - OBJECTIVE: To dynamically observe the shape of levator hiatus and the mobility of bladder neck with three dimensional transperineal ultrasound, and then to evaluate female pelvic floor in early postpartum after delivery. METHODS: 170 primiparae (the vaginal delivery group and the cesarean section group) and 35 nulliparous women were recruited, and three dimensional transperineal ultrasound were performed with standardized gynecological pelvic settings. Ultrasonic dynamic imaging information was obtained in the condition of resting, Valsalva maneuver and anal sphincter contraction, including two-dimensional midsagittal view and the three-dimensional axial plane in which some biometric measurements were determined. RESULTS: The anteroposterior diameters of levator hiatus were significantly greater on sphincter contraction in the vaginal delivery group than that in nulliparous group after the 6-8 weeks delivery, but the measurements of the levator hiatus within cesarean delivery group and nulliparous group did not show statistically significant differences (P > 0.05). The mobility of bladder neck was significantly greater on Valsalva maneuver in the vaginal delivery group than those in the other groups, while the backward motion of bladder neck was greater on Valsalva maneuver in the cesarean section group than that in nulliparous group. The incidence of postpartum stress urinary incontinence was greater in the vaginal delivery group (10/104) than that in the cesarean section group (4.5%, 3/66), but no statistically significant differences were observed (P > 0.05). CONCLUSION: The large difference of pelvic floor exists between vaginal delivery and cesarean delivery. The bladder neck decent and levator hiatus anteroposterior diameter may be relatively sensitive indicators in ultrasonic evaluation of pelvic floor muscle contraction, especially the latter may be adopted as an observation index to evaluate pelvic floor muscle recovery after delivery. PMID- 27263306 TI - [Chemical Exchange Saturation Transfer Imaging of Creatine Metabolites: a 3.0 T MRI Pilot]. AB - OBJECTIVE: To determine the feasibility of using chemical exchange saturation transfer (CEST) imaging to measure creatine (Cr) metabolites with 3.0 T MR. METHODS: Phantoms containing different concentrations of Cr under various pH conditions were studied with CEST sequence on 3.0 T MR imaging. CEST effect and Z spectra were analyzed. RESULTS: Cr exhibited significant CEST effect (+/- 1.8 ppm, F = 99.08, P < 0.001) on 3.0 T MR imaging, and positive correlation was found between the signal intensity and concentration of Cr (r = 0.963, P < 0.001). The CEST effect showed pH dependency of Cr (r = 0.41, P = 0.035). CONCLUSION: Creatine CEST imaging can be performed on 3.0 T MR imaging. Creatine concentrations and pH influence CEST effect. PMID- 27263307 TI - [Using 9-color Flow Cytometry Immunophenotyping to Detect Activation and Apoptosis of Human TCR Vbeta Lymphocyte Subpopulations in Peripheral Blood Samples]. AB - OBJECTIVE: To establish an assay using 9-color flow cytometry immunophenotyping to detect activation and apoptosis of human TCR Vbeta lymphocyte subpopulations in peripheral blood samples. METHODS: We used 5 antibodies (CD3, CD4, CD8, CD95, CD69), phospholipids binding proteins Annexin V, TCR Vbeta Repertoire Kit and nucleus dye DAPI to establish a 9-color flow cytometry assay. Peripheral blood samples were taken from eight healthy people for test of antibodies and determination of optimal PMT and staining method (single-stained vs stained with all but one antibody). RESULTS: Appropriate detecting voltage, antibody concentration and compensation methods were determined. The distribution of TCR Vbeta subgroup in our samples was consistent with the TCR Vbeta Repertoire Kit instruction and other published literature. CONCLUSION: We have established a effective easy using 9-color flow cytometry immunophenotyping to detect human TCR Vbeta lymphocyte subpopulations in peripheral blood samples. PMID- 27263308 TI - [Clinical Trial of Intraoperative Tissue Identification for Breast-Conserving Surgery Using Bio-impedance Spectroscopy]. AB - OBJECTIVE: To evaluate the effectiveness of bio-impedance spectroscopy (BIS) analysis for marginal tissue malignancy/benignancy identification during Breast Conserving Surgery (BCS). METHODS: A multicenter parallel-group clinical trial was conducted with the patients who received breast conserving surgery in 2 hospitals. One hundred and fifty breast tissue specimens were collected and analyzed by BIS, frozen section biopsy and paraffin section biopsy respectively. Results were compared and statistical analysis was implemented. RESULTS: For BIS technique to identify malignant/benign marginal tissues, the sensitivity was 92.98%, and the specificity was 94.62%. The coherence of BIS results and frozen section biopsy results was significant, and the Kappa value was higher than 0.75. The mean measuring time of BIS was 2.63 min, which was shorter than frozen section biopsy (18.97 min) and paraffin section biospy (1.12 d). CONCLUSION: BIS technique likely has high accuracy in tissue identification so has potential to be adopted as a real-time indicator for marginal tissue malignancy/benignancy identification during breast-conserving surgery. PMID- 27263309 TI - [Characteristics of Clinicopathology and Genotype in 179 Cases with Gastrointestinal Stromal Tumor]. AB - OBJECTIVE: To analyze the characteristics of the clinicopathology and genotypes in patients with gastrointestinal stromal tumor (GIST). METHODS: The clinicopathological and genotypic data of 179 patients with GIST, who underwent treatment and genetic testing in the Hostital of West China from September 2009 to February 2009 were collected retrospectively. RESULTS: The tumor sites of the cases were located in stomach (88 cases, 49.2%), small intestine (70 cases, 39.1%), colorectum (7 cases, 3.9%) and the other sites (14 cases, 7.8%) respectively. 94.4%, 74.9% and 93.3% of GIST patients were positive for CD117, CD34 and DOG-1 immunophenotypes respectively. C-kit and PDGFRalpha mutations were found in 151 cases (84.4%) and 8 cases (4.5%) except for the wild types of the rest 20 cases (11.2%). Among all the c-kit mutation, 92.2% mutation types in exon 11 were deletion mutation, point mutation and hybrid mutations, and in exon 9 the mutation types were just involving A502_Y503dup (n = 6) and Y403_F504ins (n = 14), while the mutation type were K642Q in exon 13 (n = 1) and N822K in 17 (n = 2). There were 6 patients with the mutation types of PDGFRalpha in exon 18, and 3 of them were type of D842V. In the GIST genotyping, DOG-1 positive rate in PDGFRalpha mutation patients were significantly lower than that in c-kit mutation and wild type patients (P = 0.007). In the various type of c-kit mutations, the positive rate of CD34 in point mutation patients were significantly lower than that in other mutation types (P < 0.001). The rate of high-risk patients in point mutation and insertion mutation patients were lower than that in deletion mutation and deletion + insertion mutation patients (P = 0.006). CONCLUSION: The most common localizaions of GISTs are the stomach and small intestine. The most frequent mutation type of GIST is c-kit exon 11. The individualized treatment is required for GIST patients because its high mutation rate and types. PMID- 27263310 TI - [Effect of Epidural Volume Extension on Combined Spinal-anesthesia of Parturients in Women Undergoing Cesarean Delivery]. AB - OBJECTIVE: To evaluate the blocking characteristics of epidural volume extension on combined spinal-anesthesia of parturients undergoing cesarean delivery. METHODS: Eighty parturients were randomly allocated to one of four groups, receiving 0, 5, 10 or 15 mL normal saline, respectively, through epidural catheter at a rate of 0.5 mL/s (n = 20 in each group) after combined spinal anesthesia with 11 mg intrathecally isobaric bupivacaine. Peak sensory block height, time for sensory block to sixth thoracicdermatome level, time for highest modified Bromage motor score, time for sensory regression to tenth thoracicdermatome level, and motor block recovery to Modified Bromage 0 were recorded. RESULTS: The groups with 10 mL and 15 mL epidural extension had a higher level of peak sensory and shorter time for the sensory block to sixth thoracicdermatome level compared with the control group (P< 0.05). There were no significant group differences in the time for sensory regression to tenth thoracicdermatome level (P > 0.05). The saline epidural extension groups had significant shorter time for highest modified Bromage motor score and motor block recovery to Modified Bromage 0 compared with the control group (P < 0.05). The use of phenylephrine was significantly higher in the 15 mL treatment group (P < 0.05). CONCLUSION: 10 mL of epidural saline volume extension is optimal for combined spinal-epidural anaesthesia of parturients undergoing caesarean delivery. PMID- 27263311 TI - [The Effect of Different Positions on Block Plane of Isobaric Bupivacaine for Caesarean Section with Combined Spinal-Eqidural Analgesia]. AB - OBJECTIVE: To evaluate the effect of horizontal and trendelenburg left lateral position on the onset time and the spread of intrathecal isobaric bupivacaine for elective cesarean delivery. METHODS: 180 parturients were enrolled to undergo elective cesarean delivery with combined spinal-epidural anesthesia (CSE). They were randomly divided into 3 groups (n = 60) according to the different positions during anesthesia: Group I horizontal position, Group II trendelenburg position 5 degrees, Group III trendelenburg position 10 degrees. A combined spinal-eqidural (CSE) analgesia was performed at the L3-4 interspace in either horizontal or trendelenburg left lateral position, according to randomization. 2 mL of 0.5% isobaric bupivacaine was injected into subarachnoid space when cerebrospinal fluid outflew. Then the patient was placed in a supine position. The success criteria of anesthesia was: T6 sensory block, Bromage grade 2 or 3 (motor block), anesthesia effect >= grade III. The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), sensory block, motor block and adverse reactions such as hypotension, bradycardia, chest distress were observed after the 3 groups parturients entered into operating room. The numbers and success rate of Group I, II and III which got T6 sensory block in ten minutes were observed. RESULTS: Among Group I, II and III, there were no significant differences in onset time of sensory block and motor block (P > 0.05). The cold and pinprick sensation level in 10 min of Group I1 and Group III were higher than that of Group I (P < 0.05). The success rate of Group II or III was higher than Group I (P < 0.05). The success rate of Group III was higher than that of Group II, but not with significant difference (P > 0.05). There were no significant differences in hemodynamics, adverse reactions such as hypotension, bradycardia, chest distress among three groups (P > 0.05). CONCLUSION: The trendelenburg 5 degrees position can meet the requirement of operation without high anesthesia level. PMID- 27263312 TI - [Clinical Efficacy of Second-generation Tyrosine Kinase Inhibitor in Treating Chronic Myeloid Leukemia]. AB - OBJECTIVE: To evaluate the efficacy of second-generation tyrosine kinase inhibitor (TKI) in treating chronic myeloid leukemia (CML). METHODS: A total of 97 patients with CML were enrolled. The patients were treated with TKI and monitored with complete blood count, cytogenetic and molecular indicators during the course of therapy. Survival analysis was performed to evaluate its clinical efficacy. RESULTS: The treatment achieved 97.9% complete hematologic response (CHR), 63.9% major cytogenetic response (MCyR), 60.0% complete cytogenetic response (CCyR) and 44.3% major molecular response (MMR) rates. Apart from CHR, better effects were shown in those indicators during chronic phase compared with progressive phase (P < 0.05). The 1-year, 2-year, 3-year and 5-year overall survival (OS) rate was (90.6 +/- 3.0)%, (80.1 +/- 4.5)%, (77.5 +/- 5.0)% and (64.6 +/- 9.3)%, respectively, compared with an event-free survival (EFS) rate of (81.1 +/- 4.0)%, (64.4 +/- 5.3)%, (56.4 +/- 6.0)% and (46.2 +/- 8.2)%, respectively. The patients had a 1-year, 2-year, 3-year and 5-year progession free survival (PFS) rate of (87.4 +/- 3.4)%, (73.2 +/- 4.9)%, (68.9 +/- 5.5)% and (57.4 +/- 8.7)%, respectively. A difference between chronic phase (better results) and progressive phase (P < 0.05) was also found in survival indicators. The first-line TKI therapy had 100% CHR, 95% MCyR, 95% CCyR and 70% MMR, compared with 97.3% CHR, 56.8% MCyR, 48.6% CCyR and 36.5% MMR for the second-line TKI therapy. Apart from CHR, the first-line therapy produced better results than the seond-line therapy (P < 0.05). CONCLUSION: CML patients in chronic phase and first-line use of TKI have better outcomes. PMID- 27263314 TI - The SAFER Matrix: A New Scoring Methodology. PMID- 27263313 TI - [Mental Disorders in Psychiatric Emergency Services of a General Hospital]. AB - OBJECTIVE: To investigate the distribution, diagnosis and treatment of patients with mental disorders in emergency department of a large general hospital. METHODS: Records of patients with mental disorders, who came for psychiatric diagnosis in the emergency department of West China Hospital of Sichuan University, during 1 July 2014 to 30 June 2015 were reviewed. Data about demographic characteristics, diagnosis and treatment of those patients were extracted and analyzed. RESULTS: A total of 520 patients were included in the analysis: 212 male (40.8%) and 308 female (59.2%). Three most common disorders were "Schizophrenia, Schizotypal disorder and Delusional disorder" (175 cases, 33.7%), "Mood disorder" (106 cases, 20.4%) and "Neurosis, Stress related and Somatoform disorder" (113, 21.7%). 50 (9.6%) patients were not confirmed with a diagnosis. CONCLUSION: Common mental disorders in the emergency service of this hospital include "Schizophrenia, Schizotypal disorder and Delusional disorder", "Mood disorder", and "Neurosis, Stress related and Somatoform disorder". Diagnosis of some patients is unclear. A wide range of treatment regimen should be made available. PMID- 27263315 TI - EP Review Project: The Joint Commission Deletes 225 Hospital Requirements. PMID- 27263316 TI - UPDATE: Texting Orders. PMID- 27263317 TI - POSTING: Spring E-dition for Accreditation and Certification Manuals. PMID- 27263319 TI - Approved: CAUTI NPSG for Nursing Care Centers. PMID- 27263318 TI - The Joint Commission and NQF Honor 2015 Eisenberg Award Recipients. PMID- 27263320 TI - Consistent Interpretation. PMID- 27263321 TI - Standards BoosterPakTM Supports Best Practices for HLD and Sterilization. PMID- 27263322 TI - Joint Commission Campaign Aims to Reduce Readmissions. PMID- 27263323 TI - Plan B. Interim Life Safety Measures Offer Fire Protection During Construction or Deficiencies. PMID- 27263324 TI - Regulating sex work: subjectivity and stigma in Senegal. AB - Senegal provides a unique example of a sub-Saharan African country with a legal framework for the regulation of commercial sex work. While registering as a legal sex worker affords women access to valuable social and medical resources, sex work is condemned by Senegalese society. Women who engage in sex work occupy a socially marginal status and confront a variety of stigmatising discourses and practices that legitimate their marginality. This paper examines two institutions that provide social and medical services to registered sex workers in Dakar: a medical clinic and a non-governmental organisation. It highlights the discourses about sex work that women encounter within these institutions and in their everyday lives. Women's accounts reveal a variety of strategies for managing stigma, from discretion and deception to asserting self-worth. As registered sex workers negotiate their precarious social position, their strategies both reproduce and challenge stigmatising representations of sex work. Their experiences demonstrate the contradictory outcomes of the Senegalese approach to regulating sex work. PMID- 27263325 TI - Local Minocycline Effect on Inflammation and Clinical Attachment During Periodontal Maintenance: Randomized Clinical Trial. AB - BACKGROUND: Minocycline microspheres (MMs) are being used to treat residual inflamed periodontal pockets during periodontal maintenance therapy (PMT), but evidence for efficacy from randomized clinical trials is lacking. The purpose of this study is to evaluate the effect of MMs plus scaling and root planing (SRP) on these sites. METHODS: Sixty patients with chronic periodontitis on 6-month PMT intervals to be followed for 1 year were randomized (51 completed the study) into two statistically similar groups, SRP + MM (aged 66.8 years) and SRP alone (aged 67 years), to treat a >=5 mm posterior interproximal pocket during PMT with a history of bleeding on probing (BOP). Group treatments were applied to the site at baseline and 6 months. Clinical attachment levels (CALs; primary outcome), probing depths (PDs), plaque, and BOP also were recorded at baseline and 6 and 12 months. In addition, gingival crevicular fluid was analyzed for an inflammation index ratio of interleukin (IL)-1beta/IL-1 receptor antagonist (ra) using enzyme linked immunosorbent assays. RESULTS: All clinical parameters improved significantly (P <0.005) from baseline in both groups with no differences between groups at any time point. CAL decreased 17% (0.9 +/- 0.8 mm) and 13% (0.7 +/- 0.9 mm) in SRP + MM and 11% (0.7 +/- 1.1 mm) and 21% (1.2 +/- 0.9 mm) in SRP at 6 and 12 months, respectively. The odds of having BOP decreased 90% (down to 38% of patients) and 95% (26%) in SRP + MM and 82% (42%) and 82% (41%) in SRP at 6 and 12 months, respectively. IL-1beta/IL-1ra decreased a significant 61% (P = 0.009) only in SRP + MM at 6 months. CONCLUSIONS: SRP of inflamed moderate pockets during 6-month PMT, with or without MMs, improves CALs, along with PDs and BOP over a 1-year period. The use of MMs did not result in an additional benefit over SRP alone. PMID- 27263326 TI - Physiotherapy as a first point of contact in general practice: a solution to a growing problem? AB - Aim To evaluate the clinical effectiveness, patient satisfaction and economic efficacy of a physiotherapy service providing musculoskeletal care, as an alternative to GP care. BACKGROUND: There is a growing demand on general practice resources. A novel '1st Line Physiotherapy Service' was evaluated in two GP practices (inner city practice, university practice). Physiotherapy, as a first point of contact, was provided as an alternative to GP care for patients with musculoskeletal complaints. Participants A convenience cohort sample of over 500 patients with a musculoskeletal complaint was assessed within the physiotherapy service. For the economic evaluation a cohort of 100 GP patients was retrospectively reviewed. METHOD: Clinical outcome measures were collected at assessment, one and six months following assessment. Patient satisfaction was collected at assessment. An economic evaluation was undertaken on the physiotherapy cohort of patients and compared to a retrospective cohort of patients (n=100) seen by a GP. This evaluation considered only the health care perspective (primary and secondary care). Societal issues such as absence from employment were not considered. RESULTS: There were no adverse events associated with the physiotherapy service. Patients reported high levels of satisfaction with the physiotherapy service. Patients managed within the 1st Line Physiotherapy Service demonstrated clinical improvements (EQ-5D-5L, Global Rating of Change) at the six-month point. There was a statistically significant difference in favour of the physiotherapy groups using a non-parametric bootstrap test; inner city practice, mean difference in costs=L538.01 (P =0.006; 95% CI; L865.678, L226.98), university practice mean difference in costs=L295.83 (P=0.044; 95% CI; L585.16, L83.69). CONCLUSION: The limitations of this pragmatic service evaluation are acknowledged. Nevertheless, the physiotherapy service appears to provide a safe and efficacious service. The service is well received by patients. There appear to be potential financial implications to the health economy. Physiotherapists, as a first point of contact for patients with musculoskeletal-related complaints, could contribute to the current challenges faced in primary care. PMID- 27263327 TI - Preparation of biodegradable gelatin/PVA porous scaffolds for skin regeneration. AB - Porous scaffolds composed of gelatin/poly (vinyl alcohol), (Gel/PVA), were prepared using combination of freeze gelation and freeze drying methods. The effect of polymer concentration, gelatin/PVA ratio, and glutaraldehyde/gelatin ratio (GA/Gel) was investigated on morphology of pores, swelling ratio, biodegradation, and skin cell culture. At optimum preparation conditions the scaffolds had uniform pore size distributions showing high swelling ratio of 23.6. The scaffolds were of biodegradable nature and almost degraded in 28 days. Human dermal fibroblast cells (HDF) were cultured on the scaffolds and MTS assay was conducted to evaluate the influence of PVA on growth and proliferation of the cells. PMID- 27263359 TI - Erratum to "Determination of the irradiation field at the research reactor TRIGA Mainz for BNCT" [J. Appl. Radiat. Isot. 67 (2009) S242-S246]. PMID- 27263360 TI - The rise of genomics. AB - A brief history of the development of genomics is provided. Complete sequencing of genomes of uni- and multicellular organisms is based on important progress in sequencing and bioinformatics. Evolution of these methods is ongoing and has triggered an explosion in data production and analysis. Initial analyses focused on the inventory of genes encoding proteins. Completeness and quality of gene prediction remains crucial. Genome analyses profoundly modified our views on evolution, biodiversity and contributed to the detection of new functions, yet to be fully elucidated, such as those fulfilled by non-coding RNAs. Genomics has become the basis for the study of biology and provides the molecular support for a bunch of large-scale studies, the omics. PMID- 27263361 TI - Microevolution of European temperate oaks in response to environmental changes. AB - This review reconstructs microevolutionary processes that allowed long-lived species as temperate oaks (Quercus petraea and Q. robur) to cope with climate change since the last glacial maximum, by assembling insights from complementary synchronic and allochronic approaches. Paleobotanical and genetic investigations show that oaks migrated at larger velocities than expected, thanks to long distance rare events and most likely human interferences. Hybridization was a key mechanism accelerating migration and enhancing species succession. Common garden experiments and genome wide association studies demonstrated that diversifying selection across large environmental gradients contributed to rapid local adaptation. Finally the review explores how lessons taken from past evolutionary scenarios may help to predict future responses of oaks to ongoing climate change. PMID- 27263362 TI - From Mendel to epigenetics: History of genetics. AB - The origins of genetics are to be found in Gregor Mendel's memoir on plant hybridization (1865). However, the word 'genetics' was only coined in 1906, to designate the new science of heredity. Founded upon the Mendelian method for analyzing the products of crosses, this science is distinguished by its explicit purpose of being a general 'science of heredity', and by the introduction of totally new biological concepts (in particular those of gene, genotype, and phenotype). In the 1910s, Mendelian genetics fused with the chromosomal theory of inheritance, giving rise to what is still called 'classical genetics'. Within this framework, the gene is simultaneously a unit of function and transmission, a unit of recombination, and of mutation. Until the early 1950s, these concepts of the gene coincided. But when DNA was found to be the material basis of inheritance, this congruence dissolved. Then began the venture of molecular biology, which has never stopped revealing the complexity of the way in which hereditary material functions. PMID- 27263366 TI - Correction to "Atomic Force Microscopy Reveals the Mechanobiology of Lytic Peptide Action on Bacteria". PMID- 27263396 TI - Polycystic kidney disease: WNTs: ligands of the polycystin complex. PMID- 27263400 TI - Messaging Affects the Behavior of African American Parents with Regards to Soft Bedding in the Infant Sleep Environment: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate the impact of specific health messages on the decisions of African American parents regarding soft bedding use, specifically related to the high degree of self-efficacy that African American parents have with regards to preventing infant suffocation vs low self-efficacy with regards to sudden infant death syndrome (SIDS) risk reduction. STUDY DESIGN: We conducted a randomized, controlled clinical trial of African American mothers of infants. The control group received standard messaging emphasizing safe sleep practices recommended by the American Academy of Pediatrics for the purposes of SIDS risk reduction. The intervention group received enhanced messaging emphasizing safe sleep practices for both SIDS risk reduction and suffocation prevention. Participants completed interviews at 2-3 weeks, 2-3 months, and 5-6 months after the infant's birth. RESULTS: Of 1194 mothers enrolled, 637 completed all interviews. The use of soft bedding both in the past week and last night declined with age (P < .001). Infants in the enhanced group had a lower rate of use of soft bedding in the past week (P = .006) and last night (P = .013). Mothers who received the enhanced message were more likely to state that they avoided soft bedding to protect their infant from suffocation. CONCLUSIONS: African American mothers who receive an enhanced message about SIDS risk reduction and suffocation prevention are less likely to use soft bedding in their infant's sleep environment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01361880. PMID- 27263401 TI - Dermatitis Artefacta Presenting as Recurrent Periorbital Cellulitis. PMID- 27263402 TI - Missed Opportunities: The Cost of Suboptimal Breast Milk Feeding in the Neonatal Intensive Care Unit. PMID- 27263404 TI - Nonpenetrating vs mechanical mesh fixation in laparoscopic inguinal hernia repair. PMID- 27263403 TI - Maternal Hemoglobin Concentration during Gestation and Risk of Anemia in Infancy: Secondary Analysis of a Randomized Controlled Trial. AB - OBJECTIVE: This study examined the relationship between maternal hemoglobin (Hb) concentration and the risk of anemia in infancy. STUDY DESIGN: This analysis included 17 193 women who entered the trial when they were >=20 years of age, no more than 20 weeks of gestation, had mild or no anemia, and delivered singleton live births. Maternal Hb concentrations were measured in the first trimester and during 24-28 weeks of gestation; infant Hb concentrations were measured at 5-7 months and 11-13 months of life. The associations between maternal Hb concentrations and infant Hb concentrations were examined. RESULTS: Maternal Hb concentrations measured during 24-28 weeks of gestation, but not in the first trimester, were correlated with infant Hb concentrations measured at either of the 2 post-partum periods. The risk of infant anemia at 5-7 months of age increased when maternal Hb concentration was <=109 g/L during 24-28 weeks of gestation (aOR, 1.95; 95% CI, 1.59-2.40) and 11-13 months of age (aOR, 1.72; 95% CI, 1.36-2.18), whereas the risk of anemia during 5-7 months of age as well as 11 13 months in infancy decreased when maternal Hb level at 24-28 weeks of gestation was 120-129 g/L (aOR for 5-7 months, 0.74 [95% CI, 0.64-0.85]; aOR for 11-13 months, 0.72 [95% CI, 0.61-0.85]), or >=130 g/L (aOR for 5-7 months, 0.75 [95% CI, 0.63-0.90]; aOR for 11-13 months, 0.89 [95% CI, 0.73-1.08]). CONCLUSIONS: Low maternal Hb concentration during 24-28 weeks of gestation was associated with an increased risk of anemia in infancy, whereas high maternal Hb concentration was associated with a reduced risk of anemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00133744. PMID- 27263405 TI - Outcomes of acute care surgical cases performed at night. AB - BACKGROUND: Acute care surgeons operate during the day and night. Time of day or night may impact the outcome because of surgeon and team fatigue, operative delays, or other unmeasured factors. METHODS: We performed matched retrospective cohort study of patients undergoing operative intervention at night by acute care surgeons over 16 months. Cases were matched on case complexity, age, and sex to daytime cases. Other confounders including comorbidities, presenting characteristics, complications, and mortality were abstracted. Outcomes differences between day and night cases were compared. RESULTS: Night cases (115) were matched 1:1 to daytime cases. Groups had similar degrees of comorbidity. Those operated at night had trends toward more hypotension and sepsis. After controlling for confounders using conditional logistic regression, surgical care at night was a potent predictor of mortality (odds ratio 30.02; 95% CI 2.33 to 387.40; P = .009) but had little impact on morbidity (odds ratio 1.34; 95% CI .77 to 2.36; P = .303). CONCLUSIONS: Emergency operations performed at night by acute care surgeons may have dissimilar outcomes compared with day cases. PMID- 27263406 TI - Embryonic cell culture in zebrafish. AB - Zebrafish embryonic cell cultures have many useful properties that make them complementary to intact embryos for a wide range of studies. Embryonic cell cultures allow for maintenance of transient cell populations, control of chemical and mechanical cues received by cells, and facile chemical screening. Zebrafish cells can be cultured in either heterogeneous or homogeneous cultures from a wide range of developmental time points. Here we describe two methods with particular applicability to chemical screening: a method for the culture of blastomeres for directed differentiation toward the myogenic lineage and a method for the culture of neural crest cells in heterogeneous cultures from early somitogenesis embryos. PMID- 27263398 TI - Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. AB - The prevalence of obesity-related glomerulopathy is increasing in parallel with the worldwide obesity epidemic. Glomerular hypertrophy and adaptive focal segmental glomerulosclerosis define the condition pathologically. The glomerulus enlarges in response to obesity-induced increases in glomerular filtration rate, renal plasma flow, filtration fraction and tubular sodium reabsorption. Normal insulin/phosphatidylinositol 3-kinase/Akt and mTOR signalling are critical for podocyte hypertrophy and adaptation. Adipokines and ectopic lipid accumulation in the kidney promote insulin resistance of podocytes and maladaptive responses to cope with the mechanical forces of renal hyperfiltration. Although most patients have stable or slowly progressive proteinuria, up to one-third develop progressive renal failure and end-stage renal disease. Renin-angiotensin aldosterone blockade is effective in the short-term but weight loss by hypocaloric diet or bariatric surgery has induced more consistent and dramatic antiproteinuric effects and reversal of hyperfiltration. Altered fatty acid and cholesterol metabolism are increasingly recognized as key mediators of renal lipid accumulation, inflammation, oxidative stress and fibrosis. Newer therapies directed to lipid metabolism, including SREBP antagonists, PPARalpha agonists, FXR and TGR5 agonists, and LXR agonists, hold therapeutic promise. PMID- 27263407 TI - Cellular dissection of zebrafish hematopoiesis. AB - Zebrafish as a model system have been instrumental in understanding early vertebrate development, especially of the hematopoietic system. The external development of zebrafish and their genetic amenability have allowed in-depth studies of multiple blood cell types and their respective genetic regulation. This chapter highlights some new data in zebrafish hematopoiesis regarding primitive and definitive hematopoiesis in the embryonic and adult fish, allowing the isolation of prospective progenitor subsets. It also highlights assays developed to examine the function of these progenitors in vivo and in vitro, allowing an evolutionary understanding of the hematopoietic system and how zebrafish can be better utilized as a model system for a multitude of hematopoietic disorders. PMID- 27263408 TI - Second harmonic generation microscopy in zebrafish. AB - Modern optical imaging has progressed rapidly with the ability to noninvasively image cellular and subcellular phenomena with high spatial and temporal resolution. In particular, emerging techniques such as second harmonic generation (SHG) microscopy can allow for the monitoring of intrinsic contrast, such as that from collagen, in live and fixed samples. When coupled with multiphoton fluorescence microscopy, SHG can be used to image interactions between cells and the surrounding extracellular environment. There is recent interest in using these approaches to study inflammation and wound healing in zebrafish, an important model for studying these processes. In this chapter we present the practical aspects of using second harmonic generation to image interactions between leukocytes and collagen during wound healing in zebrafish. PMID- 27263409 TI - Imaging blood vessels and lymphatic vessels in the zebrafish. AB - Blood vessels supply tissues and organs with oxygen, nutrients, cellular, and humoral factors, while lymphatic vessels regulate tissue fluid homeostasis, immune trafficking, and dietary fat absorption. Understanding the mechanisms of vascular morphogenesis has become a subject of intense clinical interest because of the close association of both types of vessels with pathogenesis of a broad spectrum of human diseases. The zebrafish provides a powerful animal model to study vascular morphogenesis because of their small, accessible, and transparent embryos. These unique features of zebrafish embryos permit sophisticated high resolution live imaging of even deeply localized vessels during embryonic development and even in adult tissues. In this chapter, we summarize various methods for blood and lymphatic vessel imaging in zebrafish, including nonvital resin injection-based or dye injection-based vessel visualization, and alkaline phosphatase staining. We also provide protocols for vital imaging of vessels using microangiography or transgenic fluorescent reporter zebrafish lines. PMID- 27263410 TI - An eye on light-sheet microscopy. AB - This chapter introduces the principles and advantages of selective plane illumination microscopy (SPIM) and compares it to commonly used epifluorescence or confocal setups. Due to the low phototoxicity, speed of imaging, high penetration depth, and spatiotemporal resolution, SPIM is predestined for in vivo imaging but can as well be used for in toto analysis of large fixed samples. Key points of light-sheet microscopy are highlighted and discussed priming the investigator to choose the best suitable system from the large collection of possible SPIM setups. Mounting of samples is shown and the demands for data acquisition, processing, handling, and visualization are discussed. PMID- 27263411 TI - Single neuron morphology in vivo with confined primed conversion. AB - Unraveling the structural organization of neurons can provide fundamental insights into brain function. However, visualizing neurite morphology in vivo remains difficult due to the high density and complexity of neural packing in the nervous system. Detailed analysis of neural morphology requires distinction of closely neighboring, highly intricate cellular structures such as neurites with high contrast. Green-to-red photoconvertible fluorescent proteins have become powerful tools to optically highlight molecular and cellular structures for developmental and cell biological studies. Yet, selective labeling of single cells of interest in vivo has been precluded due to inefficient photoconversion when using high intensity, pulsed, near-infrared laser sources that are commonly applied for achieving axially confined two-photon (2P) fluorescence excitation. Here we describe a novel optical mechanism, "confined primed conversion," which employs continuous dual-wave illumination to achieve confined green-to-red photoconversion of single cells in live zebrafish embryos. Confined primed conversion exhibits wide applicability and this chapter specifically elaborates on employing this imaging modality to analyze neural morphology of optically targeted single neurons in the developing zebrafish brain. PMID- 27263414 TI - Analysis of cilia structure and function in zebrafish. AB - Cilia are microtubule-based protrusions on the surface of most eukaryotic cells. They are found in most, if not all, vertebrate organs. Prominent cilia form in sensory structures, the eye, the ear, and the nose, where they are crucial for the detection of environmental stimuli, such as light and odors. Cilia are also involved in developmental processes, including left-right asymmetry formation, limb morphogenesis, and the patterning of neurons in the neural tube. Some cilia, such as those found in nephric ducts, are thought to have mechanosensory roles. Zebrafish proved very useful in genetic analysis and imaging of cilia-related processes, and in the modeling of mechanisms behind human cilia abnormalities, known as ciliopathies. A number of zebrafish defects resemble those seen in human ciliopathies. Forward and reverse genetic strategies generated a wide range of cilia mutants in zebrafish, which can be studied using sophisticated genetic and imaging approaches. In this chapter, we provide a set of protocols to examine cilia morphology, motility, and cilia-related defects in a variety of organs, focusing on the embryo and early postembryonic development. PMID- 27263413 TI - Using fluorescent lipids in live zebrafish larvae: From imaging whole animal physiology to subcellular lipid trafficking. AB - Lipids serve essential functions in cells as signaling molecules, membrane components, and sources of energy. Defects in lipid metabolism are implicated in a number of pandemic human diseases, including diabetes, obesity, and hypercholesterolemia. Many aspects of how fatty acids and cholesterol are absorbed and processed by intestinal cells remain unclear and present a hurdle to developing approaches for disease prevention and treatment. Numerous studies have shown that the zebrafish is an excellent model for vertebrate lipid metabolism. In this chapter, we review commercially available fluorescent lipids that can be deployed in live zebrafish to better understand lipid signaling and metabolism. In this chapter, we present criteria one should consider when selecting specific fluorescent lipids for the study of digestive physiology or lipid metabolism in larval zebrafish. PMID- 27263412 TI - Visualizing retinoic acid morphogen gradients. AB - Morphogens were originally defined as secreted signaling molecules that diffuse from local sources to form concentration gradients, which specify multiple cell fates. More recently morphogen gradients have been shown to incorporate a range of mechanisms including short-range signal activation, transcriptional/translational feedback, and temporal windows of target gene induction. Many critical cell-cell signals implicated in both embryonic development and disease, such as Wnt, fibroblast growth factor (Fgf), hedgehog (Hh), transforming growth factor beta (TGFb), and retinoic acid (RA), are thought to act as morphogens, but key information on signal propagation and ligand distribution has been lacking for most. The zebrafish provides unique advantages for genetics and imaging to address gradients during early embryonic stages when morphogens help establish major body axes. This has been particularly informative for RA, where RA response elements (RAREs) driving fluorescent reporters as well as Fluorescence Resonance Energy Transfer (FRET) reporters of receptor binding have provided evidence for gradients, as well as regulatory mechanisms that attenuate noise and enhance gradient robustness in vivo. Here we summarize available tools in zebrafish and discuss their utility for studying dynamic regulation of RA morphogen gradients, through combined experimental and computational approaches. PMID- 27263416 TI - Physiological recordings from the zebrafish lateral line. AB - During sensory transduction, external physical stimuli are translated into an internal biological signal. In vertebrates, hair cells are specialized mechanosensory receptors that transduce sound, gravitational forces, and head movements into electrical signals that are transmitted with remarkable precision and efficiency to afferent neurons. Hair cells have a conserved structure between species and are also found in the lateral line system of fish, including zebrafish, which serve as an ideal animal model to study sensory transmission in vivo. In this chapter, we describe the methods required to investigate the biophysical properties underlying mechanosensation in the lateral line of the zebrafish in vivo from microphonic potentials and single hair cell patch-clamp recordings to single afferent neuron recordings. These techniques provide real time measurements of hair-cell transduction and transmission following delivery of controlled and defined stimuli and their combined use on the intact zebrafish provides a powerful platform to investigate sensory encoding in vivo. PMID- 27263415 TI - Functional calcium imaging in zebrafish lateral-line hair cells. AB - Sensory hair-cell development, function, and regeneration are fundamental processes that are challenging to study in mammalian systems. Zebrafish are an excellent alternative model to study hair cells because they have an external auxiliary organ called the lateral line. The hair cells of the lateral line are easily accessible, which makes them suitable for live, function-based fluorescence imaging. In this chapter, we describe methods to perform functional calcium imaging in zebrafish lateral-line hair cells. We compare genetically encoded calcium indicators that have been used previously to measure calcium in lateral-line hair cells. We also outline equipment required for calcium imaging and compare different imaging systems. Lastly, we discuss how to set up optimal imaging parameters and how to process and visualize calcium signals. Overall, using these methods, in vivo calcium imaging is a powerful tool to examine sensory hair-cell function in an intact organism. PMID- 27263417 TI - The frequency of genes encoding exotoxin A and exoenzyme S in Pseudomonas aeruginosa strains isolated from burn patients. AB - BACKGROUND: Pseudomonas aeruginosa infections have emerged as a major infectious disease threat in recent decades with infection particularly in immunocompromised hosts. P. aeruginosa possesses several virulence factors with involvement in pathogenesis. The aim of this study was to examine the prevalence of virulence genes of toxA and toxS and to analyze their relation to antimicrobial resistance of the isolates. METHODS: In total 185 clinical isolates of P. aeruginosa were collected from burn patients. Antimicrobial susceptibility testing was done by disk diffusion method. PCR amplification was performed on extracted DNA from the isolates and the presence of encoding genes for exotoxin A (toxA) and exoenzyme S (toxS) were investigated by using specific primers. RESULTS: In disk diffusion method, the isolates showed high sensitivity to colistin sulfate (100%) followed by imipenem (41.9%). The most prevalent resistance was seen against ceftazidime (90.5%) and gentamicin (88.5%). Multidrug resistance (MDR) demonstrated in 113 isolates (76.35%). According to PCR amplification, 133 (89.8%) and 127 (85.8%) isolates possessed toxA and toxS genes respectively. The frequencies of genes among MDR strains were 102 (76.6%) for toxA and 98 (77.1%) for toxS. Eighty five MDR isolates possessed both genes (73.9%). The non-MDR strains (23.65%), harbored lower prevalence of simultaneous toxA and toxS genes (26%) compared to MDR strains. CONCLUSION: The present study established a higher frequency of MDR among P. aeruginosa isolates from burn patients. It was found that the frequency of both toxA &S genes were significantly higher in MDR strains P. aeruginosa strains. PMID- 27263418 TI - Effect of music intervention on burn patients' pain and anxiety during dressing changes. AB - For burn patients, the daily dressing process causes pain and anxiety. Although drugs can relieve them, the degree of pain during dressing changes is often moderate to severe. Therefore, relevant supporting interventions, like music as an ideal intervention, could alleviate the patient's pain. This study investigated the impact of music intervention at dressing change time on burn patients' pain and anxiety. This was a prospective, randomized clinical trial; patients were randomly assigned into control (standard intervention) and experimental groups (crystal music intervention) for five consecutive days (35 patients in each group). Patients' pain and anxiety measurements were collected before, during, and after dressing changes and morphine usage was recorded. The study period was October 2014 to September 2015. There was no difference in morphine dosage for both groups. By the fourth day of music intervention, burn patients' pain before, during, and after dressing changes had significantly decreased; anxiety on the fourth day during and after dressing changes had also significantly decreased. Nurses may use ordered prescription analgesics, but if non-pharmacological interventions are increased, such as providing timely music intervention and creating a friendly, comfortable hospital environment, patients' pain and anxiety will reduce. PMID- 27263419 TI - Construction of a cyanobacterium synthesizing cyclopropane fatty acids. AB - Microalgae have received much attention as a next-generation source of biomass energy. However, most of the fatty acids (FAs) from microalgae are multiply unsaturated; thus, the biofuels derived from them are fluid, but vulnerable to oxidation. In this study, we attempted to synthesize cyclopropane FAs in the cyanobacterium Synechocystis sp. PCC 6803 by expressing the cfa gene for cyclopropane FA synthase from Escherichia coli with the aim of producing FAs that are fluid and stable in response to oxidization. We successfully synthesized cyclopropane FAs in Synechocystis with a yield of ~30% of total FAs. Growth of the transformants was altered, particularly at low temperatures, but photosynthesis and respiration were not significantly affected. C16:1(?9) synthesis in the desA(-)/desD(-) strain by expression of the desC2 gene for sn-2 specific ?9 desaturase positively affected growth at low temperatures via promotion of various cellular processes, with the exceptions of photosynthesis and respiration. Estimation of the apparent activities of desaturases suggested that some acyl-lipid desaturases might recognize the lipid side chain. PMID- 27263420 TI - Whole-body DHA synthesis-secretion kinetics from plasma eicosapentaenoic acid and alpha-linolenic acid in the free-living rat. AB - Whole body docosahexaenoic acid (DHA, 22:6n-3) synthesis from alpha-linolenic acid (ALA, 18:3n-3) is considered to be very low, however, the daily synthesis secretion of DHA may be sufficient to supply the adult brain. The current study aims to assess whether whole body DHA synthesis-secretion kinetics are different when comparing plasma ALA versus eicosapentaenoic acid (EPA, 20:5n-3) as the precursor. Male Long Evans rats (n=6) were fed a 2% ALA in total fat diet for eight weeks, followed by surgery to implant a catheter into each of the jugular vein and carotid artery and 3h of steady-state infusion with a known amount of (2)H-ALA and (13)C-eicosapentaenoic acid (EPA, 20:5n3). Blood samples were collected at thirty-minute intervals and plasma enrichment of (2)H- and (13)C EPA, n-3 docosapentaenoic acid (DPAn-3, 22:5n-3) and DHA were determined for assessment of synthesis-secretion kinetic parameters. Results indicate a 13-fold higher synthesis-secretion coefficient for DHA from EPA as compared to ALA. However, after correcting for the 6.6 fold higher endogenous plasma ALA concentration, no significant differences in daily synthesis-secretion (nmol/day) of DHA (97.6+/-28.2 and 172+/-62), DPAn-3 (853+/-279 and 1139+/-484) or EPA (1587+/-592 and 1628+/-366) were observed from plasma unesterified ALA and EPA sources, respectively. These results suggest that typical diets which are significantly higher in ALA compared to EPA yield similar daily DHA synthesis secretion despite a significantly higher synthesis-secretion coefficient from EPA. PMID- 27263421 TI - Oral health in patients taking psychotropic medications: Results from a pharmacy based pilot study. AB - OBJECTIVES: Individuals with mental illness face an increased risk of oral disease compared with those without mental illness. The goals of this study were to examine the self-reported oral health and dental access of individuals filling psychotropic medication prescriptions and to determine whether pharmacy patients would choose to speak with a pharmacist about their oral health if given the option to do so. DESIGN: Pharmacists across 6 community pharmacies within a local chain identified and surveyed adult patients filling prescriptions for psychotropic medications. Surveys included questions about oral health, dry mouth, and dental care utilization. SETTING: Six community pharmacy locations. PARTICIPANTS: Adults (>=18 years of age) filling prescriptions for psychotropic medications. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Self-reported oral health, dental utilization, desire to discuss oral health with a pharmacist. RESULTS: Participants (N = 178) filling prescriptions were mostly (65.9%) female with a mean age of 48.2 years (SD 14.3, range 19-82 years). One in 4 (24.9%) said their mouths "always" or "frequently" felt dry; these individuals were significantly more likely to have last seen a dentist for emergency (rather than routine) treatment (P <0.01) and rated their oral health as significantly worse (P <0.001) than participants whose mouths "never" or "occasionally" feel dry. A small percentage (5.7%) requested to speak with pharmacists about oral health; they reported poorer oral health than those who opted not to speak with a pharmacist (P <0.05). CONCLUSION: One in 4 patients reported having dry mouth, and those with dry mouth reported significantly worse oral health than patients without dry mouth. Although dry mouth and poor oral health were common in this sample of individuals taking psychotropic medications, this did not consistently translate into seeking information regarding oral health. Future research will focus on pharmacist-initiated oral health interventions with high-risk patients. PMID- 27263422 TI - The prescription pickup lag, an automatic prescription refill program, and community pharmacy operations. AB - OBJECTIVES: To determine the effect of an automatic prescription refill program on the prescription pickup lag in community pharmacy. DESIGN: A post-only quasi experimental design comparing automatic and manual refill prescription cohorts for each of the 3 Centers for Medicare and Medicaid medication adherence metrics. SETTING: A 29-store community pharmacy chain in the Midwest. PARTICIPANTS: Community-dwelling patients over the age of 65 years receiving prescription medications included in the statin, renin-angiotensin-aldosterone system antagonist, or non-insulin diabetes adherence metrics. INTERVENTION: An automatic prescription refill program that initiated prescription refills on a standardized, recurrent basis, eliminating the need for patients to phone in or drop off prescription refills. MAIN OUTCOME MEASURES: The prescription pickup lag, defined as the number of days between a prescription being adjudicated in the pharmacy and the prescription being picked up by the patient. RESULTS: A total of 37,207 prescription fills were examined. There were 20.5%, 22.4%, and 23.3% of patients enrolled in the automatic prescription refill program for the statin, renin-angiotensin-aldosterone system antagonist, and diabetes adherence metrics, respectively. Prescriptions in the automatic prescription refill cohorts experienced a median pickup lag of 7 days compared with 1 day for the manual refill prescriptions. 35.2% of all manual refill prescriptions had a pickup lag of 0 days compared with 13% for automatic refills. However, 15.4% of automatic prescription refills had a pickup lag of greater than 14 days, compared with 4.8% of manual refills. CONCLUSION: Prescriptions in the automatic prescription refill programs were associated with a significantly longer amount of time in the pharmacy before being picked up by the patient. This increased pickup lag may contribute positively by smoothing out workload demands of pharmacy staff, but may contribute negatively owing to an increased amount of rework and greater inventory requirements. PMID- 27263423 TI - Photoluminescence enhancement of ZnO nanowire arrays by atomic layer deposition of ZrO2 layers and thermal annealing. AB - The effects of shell thickness and rapid thermal annealing on photoluminescence properties of one-dimensional ZnO/ZrO2 core/shell nanowires (NWs) are studied in this work. The ZnO/ZrO2 core/shell structures were synthesized by coating thin ZrO2 layers on the surface of ZnO NWs using atomic layer deposition. The morphological and structural characterization studies reveal that the ZrO2 shells have a polycrystalline structure, which are uniformly and conformally coated on the high quality single-crystal ZnO NWs. As compared with bare ZnO NWs, the ZnO/ZrO2 core/shell structures show a remarkable and continuous enhancement of ultraviolet (UV) emission in intensity with increasing ZrO2 shell thickness up to 10 nm. The great improvement mechanism of the UV emission arises from the surface passivation and the efficient carrier confinement effect of the type-I core/shell system. Moreover, it is observed that the UV emission of ZnO/ZrO2 core/shell structures after thermal annealing increases with increasing annealing temperature. The dominant surface exciton (SX) emission in the bare ZnO NWs and the ZnO/ZrO2 core/shell nanostructures has been detected in the low temperature photoluminescence spectra. A blue shift of the NBE emission peak as well as the varied decay rate of the SX emission intensity are also found in the ZnO NWs after the growth of ZrO2 shells and further thermal treatment. Our results suggest that the ZnO/ZrO2 core/shell nanostructures could be widely implemented in the optical and electronic devices in the future. PMID- 27263424 TI - Awareness and attitudes towards external auditory canal exostosis and its preventability in surfers in the UK: cross-sectional study. AB - OBJECTIVES: To determine the proportion of UK surfers aware of external auditory canal exostosis, to identify surfer characteristics associated with knowledge of the condition and to explore attitudes to earplug use. METHOD: An online, cross sectional survey of UK-based surfers. RESULTS: Of 375 surfers, 86.1 per cent (n = 323; 95 per cent confidence interval = 82.3-89.3) reported awareness of external auditory canal exostosis. Further investigation revealed that, despite their awareness of the condition, 23.4 per cent of these surfers (88 out of 323; 95 per cent confidence interval = 19.5-28.0) had little or no knowledge about external auditory canal exostosis. Predictors of knowledge included: distance from nearest surfing beach (p = 0.001), surfing standard (ability) (p = 0.008), earplug use (p = 0.024) and positive external auditory canal exostosis diagnosis (p = 0.009). CONCLUSION: The findings suggest that a significant minority of UK surfers have no knowledge about this condition. Knowledge of external auditory canal exostosis was significantly associated with earplug use when surfing. Efforts to improve surfers' knowledge are required to enable surfers to better protect themselves, which could reduce the incidence of external auditory canal exostosis. PMID- 27263425 TI - Combining cytology and microcrystal detection in nonpurulent joint fluid benefits the diagnosis of septic arthritis. AB - OBJECTIVE: To evaluate the performance of combined cytology and microcrystal detection in joint fluid for diagnosing septic arthritis. METHODS: Retrospective single-center study of joint fluid samples from patients with manifestations suggesting acute or chronic arthritis. The absolute leukocyte count (/mm3) was recorded; as well as the differential counts, particularly of neutrophils (%). Microcrystals were sought and bacteriological cultures performed. Septic arthritis was defined as positive cultures of joint fluid or blood samples. Diagnostic performance was assessed based on sensitivity, specificity, the receiver-operating characteristics (ROC) curve with the area under the curve (AUC), and the positive and negative likelihood ratios (LR+ and LR-). RESULTS: Two hundred and eight joint fluid samples were included. The diagnoses were septic arthritis (n=28), chondrocalcinosis (n=41), gout (n=28), rheumatoid arthritis (n=33), spondyloarthritis (n=31), osteoarthritis (n=18), and undifferentiated arthritis (n=29). Among cytological parameters, those having the best diagnostic performance were the neutrophil count (cutoff, >50,000/mm3), the leukocyte count (cutoff, >50,000/mm3), and the percentage of neutrophils (cutoff, >95%); corresponding LR+ values were 8.93, 5.76, and 4.55, respectively. Neutrophil percentages lower than 80% had an LR- value of 0.07. Combining these cytological variables with the absence of crystals improved the diagnostic performance, yielding LR+ values of 11.36, 10.94, and 10.82 for neutrophils >95%, neutrophils >50,000/mm3, and leukocytes >50,000/mm3, respectively. CONCLUSION: Combining cytological characteristics of joint fluid with the absence of crystals benefits the diagnosis of septic arthritis. PMID- 27263426 TI - Neuralgic amyotrophy. An update. AB - A century after the first description of neuralgic amyotrophy (NA), its pathophysiology remains unknown. An inflammatory (auto)immune pathophysiology is presumed, with mechanical or infectious precipitating conditions, which triggers attacks. Clinically, NA is an acute and painful unique or multiple mononeuropathy that causes palsy, amyotrophy and sensory loss in an asymmetric and patchy distribution. It involves the upper brachial plexus rather than the other parts but also may involve the cervical plexus, lumbosacral plexus and cranial nerves. The impairment can be restricted to one fascicule of one nerve, plexus or root; limited to a few ones; or extensive, involving both upper limbs. Its evolution is usually monophasic and auto-limited and never leads to generalized polyneuropathy. Electrodiagnostically, NA is characterized by severe axonal damage. The recovery is usually good after 6 months to 3 years in 80% of cases. Persistent disability is present in 20% of idiopathic NA cases and is more frequent in hereditary NA, with frequent recurrences, more frequent bilateral impairment, and more atypical distribution (cervical plexus, lumbosacral plexus or cranial nerves) than with idiopathic NA. Hereditary NA is mainly linked to a mutation in the gene of the Septin-9 protein. When the patient is seen early after disease onset, treatment with corticosteroids for 2 weeks seems to shorten the pain duration and the delayed recovery. With diagnosis during the palsy period, treatment is based on pharmacologic and non-pharmacologic therapies according to the complaints of the patient. PMID- 27263427 TI - Large amplitude motion of the acetylene molecule within acetylene-neon complexes hosted in helium droplets. AB - Superfluid helium droplets provide an ideal environment for spectroscopic studies with rotational resolution. Nevertheless, the molecular rotation is hindered because the embedded molecules are surrounded by a non-superfluid component. The present work explores the dynamical role of this component in the hindered rotation of C2H2 within the C2H2-Ne complex. A HENDI experiment was built and near-infrared spectroscopy of C2H2-Ne and C2H2 was performed in the spectral region overlapping the nu3/nu2 + nu4 + nu5 Fermi-type resonance of C2H2. The comparison between measured and simulated spectra helped to address the above issue. PMID- 27263428 TI - Formation of Volatile Tea Constituent Indole During the Oolong Tea Manufacturing Process. AB - Indole is a characteristic volatile constituent in oolong tea. Our previous study indicated that indole was mostly accumulated at the turn over stage of oolong tea manufacturing process. However, formation of indole in tea leaves remains unknown. In this study, one tryptophan synthase alpha-subunit (TSA) and three tryptophan synthase beta-subunits (TSBs) from tea leaves were isolated, cloned, sequenced, and functionally characterized. Combination of CsTSA and CsTSB2 recombinant protein produced in Escherichia coli exhibited the ability of transformation from indole-3-glycerol phosphate to indole. CsTSB2 was highly expressed during the turn over process of oolong tea. Continuous mechanical damage, simulating the turn over process, significantly enhanced the expression level of CsTSB2 and amount of indole. These suggested that accumulation of indole in oolong tea was due to the activation of CsTSB2 by continuous wounding stress from the turn over process. Black teas contain much less indole, although wounding stress is also involved in the manufacturing process. Stable isotope labeling indicated that tea leaf cell disruption from the rolling process of black tea did not lead to the conversion of indole, but terminated the synthesis of indole. Our study provided evidence concerning formation of indole in tea leaves for the first time. PMID- 27263431 TI - [Editor's commentary]. PMID- 27263429 TI - Evidence for an immune signature of prenatal alcohol exposure in female rats. AB - Evidence for immune/neuroimmune disturbances as a possible root cause of a range of disorders, including neurodevelopmental disorders, is growing. Although prenatal alcohol exposure (PAE) impacts immune function, few studies to date have examined immune function in relation to long-term negative health outcomes following PAE, and most have focused on males. To fill this gap, we utilized a rat model to examine the effects of PAE on immune/neuroimmune function during early-life [postnatal day 1 (P1), P8, and P22] in PAE and control females. Due to the extensive interplay between the immune and endocrine systems, we also measured levels of corticosterone and corticosterone binding globulin (CBG). While corticosterone levels were not different among groups, CBG levels were lower in PAE offspring from P1 to P8, suggesting a lower corticosterone reservoir that may underlie susceptibility to inflammation. Spleen weights were increased in PAE rats on P22, a marker of altered immune function. Moreover, we detected a unique cytokine profile in PAE compared to control offspring on P8 - higher levels in the PFC and hippocampus, and lower levels in the hypothalamus and spleen. The finding of a specific immune signature in PAE offspring during a sensitive developmental period has important implications for understanding the basis of long-term immune alterations and health outcomes in children with Fetal Alcohol Spectrum Disorder (FASD). Our findings also highlight the future possibility that immune-based intervention strategies could be considered as an adjunctive novel therapeutic approach for individuals with FASD. PMID- 27263430 TI - Repeating patterns of sleep restriction and recovery: Do we get used to it? AB - Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and 'catching up' on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4h followed by two nights of 8-h recovery sleep. In an intra individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p<0.05) and week 3 (p<0.09). Serum cortisol showed a significantly dysregulated 24h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect. PMID- 27263433 TI - [The effect of the I/D polymorphism of the angiotensin-converting enzyme gene on the cardiovascular risk and graft survival of kidney transplant patients]. AB - INTRODUCTION: Renal transplantation provides longer life expectancy in patients with renal failure. Nonetheless, this improved life expectancy is still shorter than that for the general population. The main couse of death in renal transplant patients is cardiovascular disease, and chronic allograft nephropathy is the most significant cause of graft loss. Genetic polymorphisms of the renin angiotensin system have been implicated in both chronic allograft nephropathy and fatal cardiovascular diseases. AIM: The long term goal of the authors was to improve the survival of renal transplanted patients. The authors aimed to identify novel biomarkers which correlate with the survival of the transplant organ and the recipient with a special attention to elements of the renin-angiotensin system. METHOD: A retrospective clinical trial was performed involving 72 renal transplanted patients. Angiotensin-converting enzyme I/D genotypes and activity, kidney function and morphological properties of the heart were determined. RESULTS: A significant positive correlation was found between the DD genotype of the angiotensin-converting enzime gene, and the DD genotype predicted severe left ventricular hypertrophy. CONCLUSIONS: These findings suggest that the I/D genotypes of the angiotensin-converting enzyme gene predict not only the expected survival of the transplanted organ, but also that of the patient. Patients with the DD genotype are more susceptible for transplant failure. These patients should be identified and a special attention should be made on their pharmacological treatment (renin-angiotensin system inhibition), and their complience should also be maintained. PMID- 27263432 TI - [First outcomes, since being full member of Eurotransplant. A single center experience of cadaveric kidney transplantation]. AB - INTRODUCTION: The first renal transplantation was completed in 1991 at the University of Debrecen. In 2013 Hungary joined Eurotransplant. AIM: The authors retrospectively compared the trends. METHOD: Comparison between Period A (from January 1, 2008 to August 31, 2013) and Period B (from September 1, 2013 to October 22, 2015). RESULTS: The proportion of living transplants rose from 3.5% to 9.1 %. During period B over 25% of utilized donors were over 60 years of age. Recipients with body mass index above 30 kg/m(2) increased from 12% to 31%. Prevalence of diabetes among recipients rose twofold. Uretero-neocystostomy was used during period A (99%) while in period B end to side uretero-ureteral anastomosis has also gained popularity (68%). In 2013 the authors introduced routine use of induction treatment. Acute rejection rate decreased from 34% to 8%. The rate of surgical complications did not change. Acute bacterial infections decreased from 41% to 33%. Cumulative renal allograft 1, 3 and 5 year survival rates were 86.6%, 85% and 82.7% in group A vs. projected rates 88%, 84% and 84% in group B, respectively. CONCLUSIONS: Despite the growing proportion of expanded criteria donors, the authors were able to maintain a low incidence of delayed graft function and a favorable graft survival. Since 2013 the authors introduced treatments for acute humoral rejection according to international standards. PMID- 27263434 TI - [Analysis of donor scoring systems in a single Hungarian transplant centre]. AB - INTRODUCTION: To ease organ shortage many transplant centres developed different donor scoring systems, however, a general consensus among clinicians on the use of these systems does not still exist. AIM: The aim of the authors was to analyse the effect of expanded criteria donor, deceased donor score and kidney donor risk index on postoperative kidney function and graft survival. METHOD: Analysis of the characteristics of 138 kidney transplantations and 205 donors in a retrospective study of a five-year period. RESULTS: There was a trend towards rejecting donors in higher risk groups; 22.7% of standard criteria donors belonged to the high risk group of deceased donor score. Graft function was worse in high risk patients. High risk donors can be divided due to the use of deceased donor score. Patients with the highest risk had worse graft function and survival. CONCLUSIONS: With the use of these scoring systems grafts with favourable outcome can be selected more precisely. PMID- 27263435 TI - [Allograft nephrectomy - a single-center experience]. AB - INTRODUCTION: Indication and timing of allograft nephrectomy is still uncertain in some cases. AIM: The aim of the authors was to summarize their experience with graftectomies. METHOD: Data from patients who underwent kidney transplantation between January 1, 2004 and December 31, 2015 were retrospectively analyzed. Frequency, indications, timing, complications as well as early and late allograft nephrectomies were reviewed. RESULTS: From 480 renal transplants, 55 graftectomies were performed (11%). Frequent indications included chronic allograft nephropathy (47%), arterial blood supply complications (13%), ureter complications (9%). 22 cases (40%) of allograft nephrectomies were urgent while 33 cases (60%) were elective. 24% of graftectomies were performed within 30 days after transplantation and 76% thereafter. CONCLUSIONS: The main indications for early graftectomies were arterial complications (31%) and chronic allograft nephropathy (62%) in cases of late graftectomies. The majority of the graftectomies were elective. Leading indication was chronic allograft nephropathy. Early and late graftectomies have different characteristics. PMID- 27263436 TI - [Treatment options of non-melanoma skin tumors in organ transplant recipients in relation to a case report]. AB - The authors present the case of a 59-year-old male patient, whose first kidney transplantation was in 1983 and the second in 2000. The first squamous cell carcinoma appeared on the skin 2 years after the first transplantation. Since 2003, at least two precancerous lesions or non-melanoma skin tumors have been removed surgically yearly. These cancers appeared predominantly on the sun exposed skin, and were multiple. As these tumors could behave aggressively and prone to recurrence, complex treatment was applied, which included a switch in immunosuppressive drugs and the application of field therapies. The authors give an overview of these treatment options in relation to the case presentation, emphasizing that not only early detection and active treatment of the precancerous lesions and skin cancers are essential, but education of proper sun protection methods and dermatology care are also important in order to avoid the development of these tumors. PMID- 27263437 TI - Synthesis and biological evaluation of 13alpha-estrone derivatives as potential antiproliferative agents. AB - 13alpha-Estrone derivatives containing various substituents on C-3 and C-17 were synthesized, and evaluated by means of MTT assays for in vitro antiproliferative activity against a panel of human adherent cancer cell lines (HeLa, MCF-7, A2780 and A431). Compounds with N-benzyltriazolylmethoxy moieties on C-3 proved to be more potent than their 3-hydroxy or 3-ether counterparts. Some triazoles exerted substantial cytostatic effects against particular tumor cell lines, with submicromolar IC50 values. PMID- 27263438 TI - Synthesis and antiproliferative activity evaluation of steroidal imidazo[1,2 a]pyridines. AB - An elegant approach to unknown steroidal imidazo[1,2-a]pyridine hybrids is disclosed. Unique derivatives of androstene and estrane series containing imidazo[1,2-a]pyridine motifs were prepared from 17-ethynyl steroids in good yields via copper-catalyzed cascade aminomethylation/cycloisomerization with imines. The synthesized compounds were screened for cytotoxicity against human breast (MCF-7, MDA-MB-231, HBL-100, MDA-MB-453) and prostate (LNCaP-LN3, PC-3, DU 145) cancer cell lines. The majority of tested compounds showed activities at MUM level in breast cancer cells. The hormone-responsive breast cancer cells MCF-7 were more sensitive to novel compounds than ERalpha-negative cells; in particular, compounds 6a,b exhibited promising cytotoxicity against this cell line with the IC50 values in the range of 3-4MUM. Furthermore, compound 4a showed remarkable effects as a selective ERalpha receptor modulator. PMID- 27263439 TI - Electrochemical cholesterylation of sugars with cholesteryl diphenylphosphate. AB - Electrochemical cholesterylation of various sugars with cholesteryl diphenylphosphate was studied. The reaction afforded mono-, di-, tri-, and tetra cholesterylated products using equivalent amounts of the reagent. The reactions turned out to be completely stereoselective with respect to both sugar and steroid but only partially regioselective - primary and anomeric hydroxyl groups in sugars were the most reactive ones while no substantial differences in reactivity was found for different secondary hydroxyl groups. PMID- 27263440 TI - This Month in AJP. AB - The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology. PMID- 27263442 TI - A four-directional non-fullerene acceptor based on tetraphenylethylene and diketopyrrolopyrrole functionalities for efficient photovoltaic devices with a high open-circuit voltage of 1.18 V. AB - Through the conjunction of tetraphenylethylene and diketopyrrolopyrrole functionalities, a novel four-directional non-fullerene electron acceptor (denoted as 4D) was designed, synthesized and characterized. The new chromophore is highly soluble (for instance >30 mg mL(-1) in o-dichlorobenzene), thermally stable, and exhibits energy levels matching those of the conventional and routinely used donor polymer poly(3-hexyl thiophene). A power conversion efficiency of 3.86% was obtained in solution-processable bulk-heterojunction devices with a very high open circuit voltage of 1.18 V. PMID- 27263441 TI - Large transverse Hall-like signal in topological Dirac semimetal Cd3As2. AB - Cadmium arsenide (Cd3As2) is known for its inverted band structure and ultra-high electron mobility. It has been theoretically predicted and also confirmed by ARPES experiments to exhibit a 3D Dirac semimetal phase containing degenerate Weyl nodes. From magneto-transport measurements in high quality single crystals of Cd3As2, a small effective mass m(*) ~ 0.05 me is determined from the Shubnikov de Haas (SdH) oscillations. In certain field orientations, we find a splitting of the SdH oscillation frequency in the FFT spectrum suggesting a possible lifting of the double degeneracy in accord with the helical spin texture at outer and inner Fermi surfaces with opposite chirality predicted by our ab initio calculations. Strikingly, a large antisymmetric magnetoresistance with respect to the applied magnetic fields is uncovered over a wide temperature range in needle crystal of Cd3As2 with its long axis along [112] crystal direction. It reveals a possible contribution of intrinsic anomalous velocity term in the transport equation resulting from a unique 3D Rashba-like spin splitted bands that can be obtained from band calculations with the inclusion of Cd antisite defects. PMID- 27263443 TI - Xanthomata striata palmaris regression with fenofibrate in type III dyslipoproteinemia: A clinical report. PMID- 27263445 TI - Radiation Therapy For The Solitary Plasmacytoma. AB - Plasma-cell neoplasms are classically categorized into four groups as: multiple myeloma (MM), plasma-cell leukemias, solitary plasmacytomas (SP) of the bone (SPB), and extramedullary plasmacytomas (EMP). These tumors may be described as localized or diffuse in presentation. Localized plasma-cell neoplasms are rare, and include SP of the skeletal system, accounting for 2-5% of all plasma-cell neoplasms, and EMP of soft tissue, accounting for approximately 3% of all such neoplasms. SP is defined as a solitary mass of neoplastic plasma cells either in the bone marrow or in various soft tissue sites. There appears to be a continuum in which SP often progresses to MM. The main treatment modality for SP is radiation therapy (RT). However, there are no conclusive data in the literature on the optimal RT dose for SP. This review describes the interrelationship of plasma-cell neoplasms, and attempts to determine the minimal RT dose required to obtain local control. PMID- 27263444 TI - Self-assembled IR780-loaded transferrin nanoparticles as an imaging, targeting and PDT/PTT agent for cancer therapy. AB - Combination of photothermal and photodynamic therapy (PTT/PDT) offer unique advantages over PDT alone. However, to achieve synergetic PDT/PTT effect, one generally needs two lasers with different wavelengths. Near-infrared dye IR-780 could be used as photosensitizer both for PTT and PDT, but its lipophilicity limits its practical use and in vivo efficiency. Herein, a simple multifunctional IR780-loaded nanoplatform based on transferrin was developed for targeted imaging and phototherapy of cancer compatible with a single-NIR-laser irradiation. The self-assembled transferrin-IR780 nanoparticles (Tf-IR780 NPs) exhibited narrow size distribution, good photo-stability, and encouraging photothermal performance with enhanced generation of ROS under laser irradiation. Following intravenous injection, Tf-IR780 NPs had a high tumor-to-background ratio in CT26 tumor bearing mice. Treatment with Tf-IR780 NPs resulted in significant tumor suppression. Overall, the Tf-IR780 NPs show notable targeting and theranostic potential in cancer therapy. PMID- 27263446 TI - The protection of the myocardium by amifostine against mitoxantrone-induced acute cardiotoxicity in rats. AB - OBJECTIVE: Amifostine (AMI) has been used for the prevention of doxorubicin induced cardiotoxicity in several experimental and a few clinical studies. The aim of this study was to investigate the effects of AMI on lipid peroxidation, protective enzymes, and mitoxantrone (MITO)-induced acute cardiotoxicity in the rat heart using biochemical tests and histopathological examinations. METHODS: Thirty-six rats were divided into six groups (n=6 in each). Control rats were given intraperitoneal (i.p.) serum saline and AMI group rats were given 200 mg/kg AMI i.p. Rats received MITO-2.5 and 5 mg/kg i.p. in the MITO-2.5 and MITO-5 groups. AMI 200 mg/kg i.p. was administered 30 min. before the same doses of MITO in the MITO-2.5+AMI and MITO-5+AMI groups. RESULTS: The levels of cardiac enzymes such as creatinine phosphokinase-myocardial band and cardiac troponin T did not change. Malondialdehyde (MDA) levels increased in MITO groups compared to controls. Catalase and glutathione (GSH) levels in the MITO and MITO+AMI groups were higher than in controls. Superoxide dismutase and glutathione peroxidase levels were not different between MITO groups and controls. There was no difference in MDA levels between MITO+AMI groups and controls. Calcium deposition was not detected. The scores of fibrosis, apoptosis, inflammation, and degeneration in MITO groups were higher than in controls. The scores of fibrosis, degeneration and inflammation in MITO+AMI groups were lower. CONCLUSION: MITO caused lipid peroxidation and myocardial damage, and the myocardium increased catalase and GSH levels to prevent this damage. AMI can protect against MITO induced acute cardiotoxicity, decreasing myocardial damage and lipid peroxidation. PMID- 27263447 TI - Functional proteomic analysis of Ankaferd(r) Blood Stopper. AB - OBJECTIVE: Ankaferd(r) Blood Stopper (ABS) comprises a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. The basic mechanism of action for ABS is the formation of an encapsulated protein network that provides focal points for vital erythrocyte aggregation. ABS-induced protein network formation with blood cells, particularly erythrocytes, covers the primary and secondary hemostatic system without disturbing individual coagulation factors. METHODS: To understand the effect mechanisms of ABS on hemostasis, a proteomic analysis using 2D gel electrophoresis and mass spectrometer was performed. RESULTS: Proteins of plant origin in Ankaferd(r) were NADP-dependent-malic enzyme, ribulose bisphosphate carboxylase-large chain, maturase K, ATP synthase subunit-beta, ATP synthase subunit-alpha, chalcone-flavanone isomerase-1, chalcone-flavanone isomerase-2, and actin-depolymerizing factor. Furthermore, functional proteomic studies revealed that proteins resembling human peptides have been detected within Ankaferd(r), including ATP synthase, mucin-16 (CD164 sialomucin-like 2 protein), coiled-coil domain containing 141 hypothetical protein LOC283638 isoform 1, hypothetical protein LOC283638 isoform 2, dynactin 5, complex I intermediate associated protein 30, mitochondrial, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, TP synthase, H+ transporting, mitochondrial actin binding 1 isoform, LIM domain and actin binding 1 isoform a, LIM domain and actin binding 1 isoform b, spectrin alpha non erythrocytic 1, prolactin releasing hormone receptor, utrophin, tet oncogene family member 2 isoform b, protein phosphatase 1 regulatory subunit 12A, NIMA (never in mitosis gene a)-related kinase, ATP binding cassette protein C12, Homo sapiens malic enzyme 1, mitochondrial NADP(+) dependent malic enzyme 3, ME2 protein, nuclear factor 1 B-type, abhydrolase domain-containing protein 12B, E3 SUMO-protein ligase PIAS2, alpha-1, 2 glucosyltransferase ALG10-A, cofilin, non-muscle isoform, 18 kDa phosphoprotein, p18, actin-depolymerizing factor (ADF), twinfilin-1, ankyrin repeat and FYVE domain-containing protein 1, usherin precursor, urotensin II receptor, interleukin 4, and midkine. CONCLUSION: Proteomic analysis of Ankaferd(r) represents a true basis for the upcoming Ankaferd(r) studies focusing on its wound healing, hemostatic, anti-infective, antineoplastic, and preservative biological actions. PMID- 27263449 TI - Enhanced platelet adhesion in essential thrombocythemia after in vitro activation. AB - OBJECTIVE: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by elevated platelet counts and increased risk of thrombosis. Ex vivo data suggest increased platelet reactivity in agreement with the increased thrombosis risk, while in vitro tests often detect decreased platelet activity. The present study aimed to investigate adhesion of ET platelets in vitro, which is an aspect of platelet function that has been addressed in only a few studies on ET patients. METHODS: The study included 30 ET patients and 14 healthy controls. Platelet adhesion was measured with a static platelet adhesion assay. RESULTS: The main finding was that ET-platelets were more readily activated by adhesion-inducing stimuli in vitro than control platelets. This was particularly evident in elderly patients and when using multiple stimuli, such as surfaces of collagen or fibrinogen combined with addition of adenosine 5'-diphosphate or ristocetin. Such multiple stimuli resulted in adhesion above the control mean +2 standard deviations for approximately 50% of the patients. CONCLUSION: The results are in accordance with the concept of increased platelet activity in ET, but opposite to most other in vitro studies. We suggest that the conditions in the adhesion assay might mimic the in vivo situation regarding the presence of chronic platelet activation. PMID- 27263448 TI - Cytotoxic T lymphocyte antigen-4 (CTLA-4) A49G polymorphism and autoimmune blood diseases. AB - OBJECTIVE: The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies. METHODS: In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA), 62 patients with immune thrombocytopenic purpura (ITP), and 150 healthy individuals. RESULTS: Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL) patients with AIHA (n=4), all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG). There was no significant statistical association between G allele and systemic lupus erythematosus (SLE) or AIHA. CONCLUSION: These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease. PMID- 27263450 TI - Clinical Aspects Of Sclerodermatous Type Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation. AB - OBJECTIVE: We aimed to evaluate the clinical features of sclerodermatous chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (AHSCT). METHODS: We retrospectively analyzed 423 patients who underwent AHSCT. We assessed age, sex, pre-transplant diagnosis, conditioning regimen, GVHD prophylaxis, and occurrence of acute GVHD (aGVHD), chronic lichenoid and chronic systemic GVHD, and clinical properties of sclerodermatous GVHD. RESULTS: Sclerotic skin lesions developed in 22 patients after a mean of 752+/-647 days (median 480). aGVHD appeared in 17 patients, with hepatic involvement in 2, gastrointestinal tract involvement in 2 and skin involvement in 13 of these patients. Extensive chronic GVHD (liver, pulmonary, skin and oral mucosa) developed in 12 patients. Sclerosis was generalized in 19 patients (86.4%) and localized in 3 patients (13.6%). Leopard skin eruption appeared in 8 (36.4%) of the 19 patients with generalized sclerodermatous changes. In most cases, sclerotic lesions appeared on the trunk, and distal parts of the extremities were spared. Eight patients (36.4%) progressed from lichenoid to sclerodermatous lesions, 2 (9.1%) with lichenoid and sclerodermatous phases together and 12 (55.5%) with de novo sclerodermatous lesions. Five patients died because of late transplant-related complications. CONCLUSION: Sclerodermatous GVHD has a late onset and may be quite disabling. Unlike scleroderma, acral involvement is seen rarely. Although most lesions do not disappear in the course of the disease, most patients have a good prognosis. PMID- 27263451 TI - New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects. AB - OBJECTIVE: We aimed to detect novel in vitro effects of clopidogrel on platelets by assessment of the following parameters: malondialdehyde, glutathione, nitrite, aggregation response, and expressions of P-selectin, fibrinogen, apolipoprotein A1, apolipoprotein B, and phosphatidylserine. METHODS: Platelets were obtained from healthy (n: 9) and hyperlipidemic (n: 9) volunteers. Expressions of P selectin, fibrinogen, apolipoproteins A1/B and phosphatidylserine with and without clopidogrel were assayed by flow cytometry. Malondialdehyde, glutathione, aggregation and nitrite levels were also assayed. RESULTS: Without clopidogrel, the baseline values of platelet aggregation, malondialdehyde, and expressions of P-selectin, fibrinogen and phosphatidylserine were significantly higher, whereas nitrite and expression of apolipoproteins A1/B were significantly lower in hyperlipidemics than in the healthy group. In both groups, clopidogrel significantly reduced aggregation and expression of fibrinogen, but it elevated nitrite levels. Clopidogrel significantly decreased P-selectin and phosphatidylserine expression and malondialdehyde but increased expressions of apolipoproteins A1/B only in hyperlipidemics. CONCLUSION: It seems that clopidogrel has some new in vitro antiplatelet effects. The present study is a basic in vitro study to suggest new insights into the effects of clopidogrel on platelet functions. PMID- 27263452 TI - A rare extramedullary involvement in myeloma: lung parenchyma and association with unfavorable chromosomal abnormalities. AB - Although pulmonary complications developing secondary to lung infections and involvement in ribs occur frequently in multiple myeloma (MM), involvement of the lung parenchyma is quite rare. In clinical studies, the involvement of lung parenchyma has been found to be associated with unfavorable prognosis. Here, a MM case in whom involvement of lung parenchyma was accompanied by unfavorable prognostic cytogenetic markers is presented. A 62-year-old male presented with complaint of cough, and heterogeneous hypodense mass was detected in thorax computerized tomography. The patient underwent bronchoscopic biopsy. Pathological examination revealed diffuse plasma cell infiltration staining with kappa immunohistochemically. In bone marrow biopsy, plasma cell infiltration was observed. In conventional cytogenetic examination, hypodiploidy was established. In cytogenetic examination carried out with fluorescence in situ hybridization, deletion (13q) was determined. In conclusion, in patients diagnosed with MM and presenting with pulmonary mass lesion, lung involvement associated with plasma cell infiltration should also be considered in the differential diagnosis. As overall survival is low in these cases, more aggressive treatment approaches such as high-dose treatment should be immediately considered. PMID- 27263453 TI - Complex cytogenetic findings in the bone marrow of a chronic idiopathic myelofibrosis patient. AB - Chronic idiopathic myelofibrosis is a myeloproliferative disorder characterized by splenomegaly, myeloid metaplasia and reactive bone marrow fibrosis. Karyotype analysis of the bone marrow is an integral part of the diagnosis, especially as a discriminative tool in ruling out reactive conditions. The frequency of clonal cytogenetic anomalies in this disease is the highest among its group, varying between 30 and 75%. Among these, trisomy 1q, 20q-, 13q- and +8 are the most common aberrations. Here we report a 66-year-old male patient whose bone marrow biopsy revealed signs of chronic myeloproliferative changes and dysmegakaryopoiesis. He was administered hydroxyurea treatment, splenic radiotherapy and multiple transfusions. The patient worsened in the following months and the second bone marrow biopsy revealed myelofibrosis. Cytogenetic analysis of this bone marrow sample revealed a complex karyotype reported to be 46,XY,del(9)(q22q34),t(8;17;21)(q22;q21;q22)[23]/46,XY[2], with a previously undefined three-way translocation and deletion in chromosome 9. The patient died shortly thereafter. PMID- 27263454 TI - An unusual presentation of pediatric acute lymphoblastic leukemia with parotid gland involvement and dactylitis. AB - Mumps infection during the course of childhood acute lymphoblastic leukemia (ALL) treatment has been reported to have a mild course and this was related to the intrinsic low cytopathological effect of the virus, contrasting with the severe course of measles and Varicella zoster virus infections in immunocompromised patients. Herein, we present a three-year-old girl, who was previously vaccinated against mumps infection, admitted with bilateral parotid swelling, dactylitis and serum immunoglobulin M positivity for mumps infection and diagnosed to have ALL with bilateral persistent parotid involvement, inconsistent with mumps infection. Acute leukemia should be suspected during the atypical course of any disease during childhood. Besides, mumps infection at presentation of ALL, as similar to infection emerging during the period of the leukemia treatment, has a mild course. PMID- 27263455 TI - First observation of Hb Tunis [beta124(H2)Pro>Ser] in Turkey. AB - Hb Tunis [beta124(H2)Pro>Ser] was reported from Tunisia in 1988. This hemoglobin variant was detected by isoelectric focusing moving just ahead of Hb A. It cannot be identified by standard hemoglobin electrophoresis due to its similar mobility to Hb A. It has normal stability and oxygen affinity and does not produce any clinical symptoms. Here, we report a heterozygous Hb Tunis [beta124(H2)Pro>Ser] case discovered for the first time in Turkey in a premarital screening program. This hemoglobin variant can be identified with high performance liquid chromatography analysis confirmed with DNA sequencing. We emphasize in our study the importance of an interdisciplinary collaborative study at the provincial basis for the success of the hemoglobinopathy control program. PMID- 27263456 TI - Ribosomal protein S19 - 631 insertion is an African-originated mutation. PMID- 27263457 TI - Lower FXII activity and thrombosis: a comment. PMID- 27263458 TI - IgA lambda oligoclonal gammopathy in multiple myeloma. PMID- 27263459 TI - Blood transfusion services in Iraq; an unfortunate field. PMID- 27263460 TI - Mega-dose methylprednisolone in hematologic and non-hematological disorders. PMID- 27263461 TI - Oseltamivir and G6PD deficiency. PMID- 27263462 TI - FLT3 - ITD positive acute lymphocytic leukemia, does it impact on disease's course? PMID- 27263463 TI - Pleural fluid plasmacytosis in a patient with plasma cell leukemia. PMID- 27263465 TI - The Dual Roles of NRF2 in Cancer. AB - NRF2 has been traditionally considered as a tumor suppressor because its cytoprotective functions are deemed to be the main cellular defense mechanism against exogenous and endogenous insults, including xenobiotics and oxidative stress. However, several recent studies demonstrate that hyperactivation of the NRF2 pathway creates an environment that favors the survival of normal as well as malignant cells, protecting them against oxidative stress, chemotherapeutic agents, and radiotherapy. In a rapidly advancing field, this review summarizes some of the known mechanisms by which NRF2 can exert its oncogenic functions, and describes the current status of NRF2 inhibitors, providing a clear rationale for the consideration of NRF2 as a powerful putative therapeutic target in cancer treatment. PMID- 27263467 TI - Highly efficient dehydrogenation of formic acid in aqueous solution catalysed by an easily available water-soluble iridium(iii) dihydride. AB - The new water-soluble cis-mer-[IrH2Cl(mtppms)3] (mtppms = monosulfonated triphenylphosphine) was employed as a catalyst for selective decomposition of formic acid to H2 + CO2 in aqueous solution at T = 30-100 degrees C. The easily synthesized compound showed high catalytic activity (TOF up to 298 000 h(-1)) and could be reused several times with no loss of activity (total TON = 67 650). A sharp maximum in the reaction rate was observed at pH = 3.75; its coincidence with the pKa of formic acid shows that both H(+) or HCOOH and HCOO(-) play important roles in the reaction mechanism. PMID- 27263464 TI - Hypo- and Hyper-Assembly Diseases of RNA-Protein Complexes. AB - A key aspect of cellular function is the proper assembly and utilization of ribonucleoproteins (RNPs). Recent studies have shown that hyper- or hypo-assembly of various RNPs can lead to human diseases. Defects in the formation of RNPs lead to 'RNP hypo-assembly diseases', which can be caused by RNA degradation outcompeting RNP assembly. By contrast, excess RNP assembly, either in higher order RNP granules, or due to the expression of repeat-containing RNAs, can lead to 'RNP hyper-assembly diseases'. Here, we discuss the most recent advances in understanding the cause of disease onset, as well as potential therapies from the aspect of modulating RNP assembly in the cell, which presents a novel route to the treatment of these diseases. PMID- 27263466 TI - Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension. AB - Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). If untreated, they can result in death due to right-sided heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. We describe in detail the role of the nitric oxide sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and pivotal phase III randomized clinical trials in PAH and CTEPH. PMID- 27263468 TI - Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides. AB - Weeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world's most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2',3',4',3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2',3',4'-Trihydroxychalcone (IC50 = 4.2 MUM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15-45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme. PMID- 27263469 TI - Kin effects on energy allocation in group-living ground squirrels. AB - The social environment has potent effects on individual phenotype and fitness in group-living species. We asked whether the presence of kin might act on energy allocation, a central aspect of life-history variation. Using a 22-year data set on reproductive and somatic allocations in Columbian ground squirrels (Urocitellus columbianus), we tested the effects of co-breeding and non-breeding kin on the fitness and energy allocation balance between reproduction and personal body condition of individual females. Greater numbers of co-breeding kin had a positive effect on the number of offspring weaned, through the mechanism of altering energy allocation patterns. On average, females with higher numbers of co-breeding kin did not increase energy income but biased energy allocation towards reproduction. Co-breeding female kin ground squirrels maintain close nest burrows, likely providing a social buffer against territorial invasions from non kin ground squirrels. Lower aggressiveness, lower risks of infanticide from female kin and greater protection of territorial boundaries may allow individual females to derive net fitness benefits via their energy allocation strategies. We demonstrated the importance of kin effects on a fundamental life-history trade off. PMID- 27263470 TI - Selective targeting of MAPK family kinases JNK over p38 by rationally designed peptides as potential therapeutics for neurological disorders and epilepsy. AB - Human mitogen-activated protein kinase (MAPK) family members JNK and p38 are two homologous protein-serine/threonine kinases but play distinct roles in the pathological process of neurological disorders. Selective targeting of JNK over p38 has been established as a potential therapeutic approach to epilepsy and other nervous system diseases. Herein, we describe an integrated in vitro-in silico protocol to rationally design kinase-peptide interaction specificity based on crystal structure data. In the procedure, a simulated annealing (SA) iteration optimization strategy is described to improve peptide selectivity between the two kinases. The optimization accepts moderate compromise in peptide affinity to JNK in order to maximize the affinity difference between peptide interactions with JNK and p38. The structural basis, energetic properties and dynamic behavior of SA-improved peptides bound with the peptide-docking sites of JNK and p38 kinase domains are investigated in detail using atomistic molecular dynamics (MD) simulations and post binding free energy analysis. The theoretical findings and computational designs are then confirmed by fluorescence polarization assays. Using the integrated protocol we successfully obtain three decapeptide ligands, namely RLHPSMTDFL, RAKLPTSVDY and KPSRPWNLEI, that exhibit both potent affinity to JNK (K = 8.0, 5.4 and 12.1 MUM, respectively) and high selectivity for JNK over p38 (K/K = 9.2, 17.9 and 6.3 fold, respectively). We also demonstrate that a JNK-over-p38 selective peptide should have a positively charged N-terminus, a polar central region and a negatively charged C-terminus, in which a number of hydrophobic residues distribute randomly along the peptide sequence. In particular, the residue positions 1, 6 and 9 play a crucial role in shaping peptide selectivity; the presence of, respectively, Arg, Thr and Asp at the three positions confers high specificity to kinase-peptide interactions. PMID- 27263471 TI - Avoiding short circuits from zinc metal dendrites in anode by backside-plating configuration. AB - Portable power sources and grid-scale storage both require batteries combining high energy density and low cost. Zinc metal battery systems are attractive due to the low cost of zinc and its high charge-storage capacity. However, under repeated plating and stripping, zinc metal anodes undergo a well-known problem, zinc dendrite formation, causing internal shorting. Here we show a backside plating configuration that enables long-term cycling of zinc metal batteries without shorting. We demonstrate 800 stable cycles of nickel-zinc batteries with good power rate (20 mA cm(-2), 20 C rate for our anodes). Such a backside-plating method can be applied to not only zinc metal systems but also other metal-based electrodes suffering from internal short circuits. PMID- 27263472 TI - Focused helium-ion beam irradiation effects on electrical transport properties of few-layer WSe2: enabling nanoscale direct write homo-junctions. AB - Atomically thin transition metal dichalcogenides (TMDs) are currently receiving significant attention due to their promising opto-electronic properties. Tuning optical and electrical properties of mono and few-layer TMDs, such as tungsten diselenide (WSe2), by controlling the defects, is an intriguing opportunity to synthesize next generation two dimensional material opto-electronic devices. Here, we report the effects of focused helium ion beam irradiation on the structural, optical and electrical properties of few-layer WSe2, via high resolution scanning transmission electron microscopy, Raman spectroscopy, and electrical transport measurements. By controlling the ion irradiation dose, we selectively introduce precise defects in few-layer WSe2 thereby locally tuning the resistivity and transport properties of the material. Hole transport in the few layer WSe2 is degraded more severely relative to electron transport after helium ion irradiation. Furthermore, by selectively exposing material with the ion beam, we demonstrate a simple yet highly tunable method to create lateral homo-junctions in few layer WSe2 flakes, which constitutes an important advance towards two dimensional opto-electronic devices. PMID- 27263473 TI - Inter-laboratory Variability of Current Immunoassay Methods for Tacrolimus among Japanese Hospitals. AB - The aim of this study was to assess inter-hospital laboratory variability (coefficient of variation; CV) of immunoassay methods for tacrolimus and the comparability of control samples and results obtained by immunoassay measurements. One hundred seven hospital laboratories routinely performing therapeutic drug monitoring (TDM) of tacrolimus participated in the study. Thirteen spiked samples with known tacrolimus concentrations in the range of 0 26.0 ng/mL were prepared. Each spiked sample was analyzed according to the manufacturer's instructions using an affinity column-mediated immunoassay (ACMIA) on a Dimension((r)) analyzer, the enzyme multiplied immunoassay technique (EMIT) on a Viva-E((r)) analyzer, a chemiluminescent enzyme immunoassay (CLIA) on the Architect((r)) system, and the electro-chemiluminescence immunoassay (ECLIA) on a cobas((r)) analyzer. The 20% coefficient of variation values for the CLIA, ACMIA, EMIT, and ECLIA assays in the hospital laboratories were 1.82, 5.36, 4.59, and 0.89 ng/mL, respectively. CLIA and ECLIA had positive biases at concentrations of tacrolimus above 12 ng/mL relative to the spiked concentration, whereas the assay bias for ACMIA tended to be more negative at concentrations of tacrolimus above 6 ng/mL. EMIT had positive biases over the wide concentration range of 0.0-26.0 ng/mL (mean of mean errors 1.224). CLIA and ECLIA provided adequate precision at the target tacrolimus concentration of 3.0 ng/mL, whereas ACMIA and EMIT were unable to respond to target concentrations between 3.0 and 5.0 ng/mL for renal transplant recipients. Appropriate assessment of tacrolimus concentration by an assay having higher sensitivity, precision, and accuracy is necessary to ensure long-term survival of transplant recipients receiving tacrolimus. PMID- 27263475 TI - Supporting Safety in the Older Adult Driver: A Public Health Nursing Opportunity. AB - The effective operation of a motor vehicle encompasses a wide range of cognitive processes that can decline due to age-related changes in neuroanatomical structures and cognitive functionality. The increasing number of older adult drivers in our rapidly aging population heightens the public safety concern of unsafe driving associated with these changes. Nurses caring for older adults in public health settings are well positioned to make a difference in the management of older patients who may be at risk of endangering themselves or others on the roadways. In this article, information is provided for increasing nurses' awareness of the cognitive factors inhibiting effective driving, recognizing older adults who may be at risk for unsafe driving, and facilitating a patient/family to seek a driving evaluation. PMID- 27263476 TI - Clinical research in Turkey. AB - The History of Clinical Drug Trials in Turkey The history of clinical trials in Turkey dates back to the beginning of the 20th century, but many years had passed with studies done with no compliance to the Good Clinical Practice (GCP) guidelines. This was not due to the lack of legal documents. On the contrary, the first mention of clinical trials in a legal document occurred in 1926; "The Code of Pharmaceutical Products and Preparations No. 1262" law carried the statement: "Experimental drugs can be used in a patient only by his/her permission." PMID- 27263474 TI - Reassessing Shark-Driven Trophic Cascades on Coral Reefs: A Reply to Ruppert et al. PMID- 27263477 TI - Seropositivity rates of HBsAg, anti-HCV, anti-HIV and VDRL in blood donors in Eastern Turkey. AB - Infections caused by hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency viruses (HIV) remain the leading most important health problems worldwide. Screening tests such as HBsAg, anti-HCV, anti-HIV and VDRL are mandatory tests to look at before transfusion of blood or blood components. In this study, donors who applied to our Blood Center in a nine-year period were retrospectively evaluated with respect to HBsAg, anti-HCV, anti-HIV and syphilis seroprevalence. HBsAg, anti-HCV and anti-HIV were examined by microparticle ELISA system, and syphilis antibodies were screened by a syphilis test device. Of the total 39,002 individuals, 16,601 (42%) were females and 22,401 (58%) were males. HBsAg positivity was found in 2.55%, anti-HCV in 0.17%, anti-HIV in 0.036%, and VDRL in 0.057% of overall donors. As a result, HBsAg, anti-HCV, anti-HIV and VDRL seropositivity rates in donors living in our region were found lower than those in many regions of Turkey. Nevertheless, because there is no screening method to reduce the risk resulting from transfusion to zero, it appears that it is essential to adopt strict criteria in the selection of donors and to avoid unnecessary transfusion. PMID- 27263478 TI - Late Endocrine Side Effects in Children with Acute Leukemia. AB - This study was carried out in 28 patients (10 female, 18 male) diagnosed with acute leukemia, and aimed to investigate the abnormalities of endocrine system. Twenty-five of 28 patients were acute lymphoblastic leukemia and 3 were acute non lymphocytic leukemia. Sixteen children were treated using BFM-90 chemotherapy protocol, and the rest with various regimens. Two patients were exposed to 12-13 Gy of total body irradiation followed by bone marrow transplantation. All patients were in remission at least five years. One (3%) of 28 patients had short stature and 4 (14%) had obesity. Pubertal status was retarded in 2 (7%) patients. Glucose intolerance, secondary hypothyroidism and hypergonadotropic hypogonadism were detected in 2, 1 and 2 patients, respectively. TSH response to TRH test was exaggerated in 1 and blunted in 3 patients. PMID- 27263479 TI - T102C polymorphism of the serotonin (5-HT) 2A receptor gene in Turkish children with cerebral infarct. AB - Platelet-dependent thromboembolism is an underlying mechanism in the pathogenesis of stroke. 5-HT2A receptor gene is expressed in human platelet, coronary artery (blood vessels) and brain. A polymorphism T102C at the 5-HT2A receptor gene was found that may possibly affect the 5-HT2A receptor function. As there is no existing data on T102C variant of 5-HT2A receptor gene in pediatric stroke, we aimed to study in this case-control study whether there is a association between this polymorphism and pediatric stroke. 111 patients (10 months-18 years old) with cerebral infarct and 79 healthy control was included to our study. Polymerase chain reaction (PCR) of the T102C alteration at the 5-HT 2A receptor gene was performed. Our data revealed that, 5-HT (2A) receptor T102C polymo phism was not associated with pediatric stroke in our population either alone or in combination with underlying pro thrombotic factors. However, this needs to be clarified with further studies. PMID- 27263480 TI - Fibrinogen concentration: A marker of cardiovascular disorders in Nigerians. AB - Fibrinogen, one of the most hemorheologically active plasma proteins, is associated with several cardiovascular risk factors, and the plasma concentration can alter dramatically during acute phase response and in a wide variety of clinical conditions. We have assessed fibrinogen levels in some known cardiovascular disorders, during usage of contraceptive pills, acute phase conditions and pregnancy. Our results from patients with various disease conditions indicate that fibrinogen levels are in the pathological range and are significantly higher than in healthy controls (p<0.001). It is concluded that although Africans have low predisposition to thrombosis, they may well be pre disposed to abnormal fibrin formation which could lead to various thromboembolic complications. PMID- 27263481 TI - Synergistic effect of imatinib mesylate and fludarabine combination on Philadelphia chromosome-positive chronic myeloid leukemia cell lines. AB - Fludarabine-containing combinations have additive cell killing against leukemic blasts in vitro. It has also been shown that imatinib mesylate combined with fludarabine or cladribine had an additive effect on CML CFU-GM cells. In this regard, we aimed to investigate the effect of fludarabine-imatinib mesylate combination against CML blastic phase cell lines K562 and Meg-01. XTT test was performed for proliferation and inhibition assay. According to obtained data, five different effective concentrations of each drug in 25 different combinations were tested. Results of the combination studies were analyzed with isobologram. At IC20, imatinib mesylate and fludarabine combination showed synergism and strong synergism in K562 and Meg-01 cells, respectively. At IC50 and IC75, combination indexes (CI) indicated strong synergism and synergism. Based on our results, the fludarabine- based chemotherapy regimens can be used for those patients with CML blastic phase in combination with imatinib mesylate. PMID- 27263482 TI - A case of Cauda Equina syndrome in a leukemic patient due to intrathecal methotrexate. AB - The leukemias may cause neurologic dysfunction through either direct invasion of the nervous system or indirectly through cytopenias, or it may occur as a result of the necessarily vigorous treatment programs for leukemia. We report here a 24 year-old acute lymphoblastic leukemia patient who in her second cycle of hyper CVAD chem therapy regimen (high-dose Ara-C and high-dose methotrexate) received intrathecal methotrexate and two days afterwards was diagnosed as having Cauda Equina syndrome (CES). A lumbo-sacral MRI imaging with gadolinium was performed and there was a remarkable enhancement in the Cauda Equina region, suggesting either leukemic involvement or a type of neurologic complication associated with intrathecal methotrexate treatment. To rule out leukemic involvement, a lumbar puncture was performed and the CSF was free of leukemic cells. There are cases of CES developing after spinal anesthesia reported in the literature, but this is the first report of CES due to intrathecal methotrexate. PMID- 27263483 TI - Intense myelofibrosis in a child: unusual result of EBV-associated hemophagocytic lymphohistiocytosis. AB - A previously healthy 12-year-old girl was admitted to the intensive care unit with severe pulmonary bleeding. Her history revealed that she had suffered from high fever, fatigue, sore throat, myalgia and generalized rash for two weeks. Physical examination revealed hepatosplenomegaly. Laboratory investigation showed pancytopenia associated with unusual high levels of serum ferritin, triglyceride and lactate dehydrogenase (LDH) and low fibrinogen levels. Apparent hemophagocytosis was seen in bone marrow aspiration. Bone marrow biopsy revealed myelofibrosis, and confirmed hemophagocytosis. IgM for Epstein-Barr virus (EBV) viral capsid antigen was found to be positive. She received chemotherapy for 10 days according to hemophagocytic lymphohistiocytosis (HLH)-2004 treatment protocol, since the symptoms persisted despite supportive therapy and intravenous immunoglobulin (IVIG) administration. However, the clinical status and laboratory findings did not respond to treatment and she died from severe pulmonary bleeding associated with prolonged ventilator support and sepsis. Intense myelofibrosis, which is reported rarely, particularly in patients with EBV-related HLH, contributed to this fatal prognosis. PMID- 27263484 TI - Bone marrow necrosis in a patient receiving high dose chemotherapy for ALL. PMID- 27263485 TI - A further case of Hb J-Iran [beta77(EF1)His->Asp] in Mugla, Turkey. PMID- 27263486 TI - Recruitments of trained citizen volunteering for conventional cardiopulmonary resuscitation are necessary to improve the outcome after out-of-hospital cardiac arrests in remote time-distance area: A nationwide population-based study. AB - AIMS: To compare the factors associated with survival after out-of-hospital cardiac arrests (OHCAs) among three time-distance areas (defined as interquartile range of time for emergency medical services response to patient's side). METHODS: From a nationwide, prospectively collected data on 716,608 OHCAs between 2007 and 2012, this study analyzed 193,914 bystander-witnessed OHCAs without pre hospital physician involvement. RESULTS: Overall neurologically favourable 1 month survival rates were 7.4%, 4.1% and 1.7% for close, intermediate and remote areas, respectively. We classified BCPR by type (compression-only vs. conventional) and by dispatcher-assisted CPR (DA-CPR) (with vs. without); the effects on time-distance area survival were analyzed by BCPR classification. Association of each BCPR classification with survival was affected by time distance area and arrest aetiology (p<0.05). The survival rates in the remote area were much higher with conventional BCPR than with compression-only BCPR (odds ratio; 95% confidence interval, 1.26; 1.05-1.51) and with BCPR without DA CPR than with BCPR with DA-CPR (1.54; 1.29-1.82). Accordingly, we classified BCPR into five groups (no BCPR, compression-only with DA-CPR, conventional with DA CPR, compression-only without DA-CPR, and conventional without DA-CPR) and analyzed for associations with survival, both cardiac and non-cardiac related, in each time-distance area by multivariate logistic regression analysis. In the remote area, conventional BCPR without DA-CPR significantly improved survival after OHCAs of cardiac aetiology, compared with all the other BCPR groups. Other correctable factors associated with survival were short collapse-to-call and call to-first CPR intervals. CONCLUSION: Every effort to recruit trained citizens initiating conventional BCPR should be made in remote time-distance areas. PMID- 27263487 TI - Channels and transporters in cell metabolism. PMID- 27263488 TI - Prevalence of hypercalcemia among cancer patients in the United States. AB - Hypercalcemia of malignancy (HCM) is a serious metabolic complication whose population-based prevalence has not been quantified. Rates of HCM differ by tumor type, with highest rates reported in multiple myeloma and lowest among colorectal and prostate cancer patients. This analysis estimates HCM prevalence in the US. This retrospective study used the Oncology Services Comprehensive Electronic Records (OSCER) warehouse of electronic health records (EHR) including laboratory values from 569000 patients treated at 565 oncology outpatient sites. OSCER data were projected to the national level by linking EHR to claims data. Cancer patients included were >=18 years, and had serum calcium (Ca) and albumin (for corrected serum Ca [CSC]) records. Period prevalence was estimated by HCM CTCAE grade, tumor type, and year (2009-2013). Estimates were adjusted to capture patients diagnosed with HCM outside oncology practices based on a subset of patients linkable to office and hospital data. The analysis included 68023 (2009) to 121482 (2013) cancer patients. In 2013, patients with HCM had a median of six Ca tests, 69.7% had chemotherapy, and 34% received bone modifying agents. HCM rates were highest for multiple myeloma patients (7.5% [2012]-10.2% [2010]), lowest for prostate cancer (1.4% [2012]-2.1% [2011]).The estimated adjusted annual prevalence of HCM from 2009 to 2013 was 95441, 96281, 89797, 70158, and 71744, respectively. HCM affected 2.0-2.8% of all cancer patients. EHR data from oncology clinics were critical for this study because these data contain results from laboratory studies (i.e., serum calcium values) that are routinely ordered in that setting. We estimated that the prevalence of HCM in the US in 2013 is 71744, affecting approximately 2% of cancer patients overall. This percentage differs by tumor type and appears to have decreased over the five-year study period. PMID- 27263491 TI - Combination of mouse models and genomewide association studies highlights novel genes associated with human kidney function. AB - Genomewide association studies have identified numerous chronic kidney disease associated genetic variants, but often do not pinpoint causal genes. This limitation was addressed by combining Mouse Genome Informatics with human genomewide association studies of kidney function. Genes for which mouse models showed abnormal renal physiology, morphology, glomerular filtration rate (GFR), or urinary albumin-to-creatinine ratio were identified from Mouse Genome Informatics. The corresponding human orthologs were then evaluated for GFR associated single-nucleotide polymorphisms in 133,814 individuals and urinary albumin-to-creatinine ratio-associated SNPs in 54,451 individuals in genome-wide association studies meta-analysis of the CKDGen Consortium. After multiple testing corrections, significant associations with estimated GFR in humans were identified for single-nucleotide polymorphisms in 2, 7, and 17 genes causing abnormal GFR, abnormal physiology, and abnormal morphology in mice, respectively. Genes identified for abnormal kidney morphology showed significant enrichment for estimated GFR-associated single-nucleotide polymorphisms. In total, 19 genes contained variants associated with estimated GFR or the urinary albumin-to creatinine ratio of which 16 mapped into previously reported genomewide significant loci. CYP26A1 and BMP4 emerged as novel signals subsequently validated in a large, independent study. An additional gene, CYP24A1, was discovered after conditioning on a published nearby association signal. Thus, our novel approach to combine comprehensive mouse phenotype information with human genomewide association studies data resulted in the identification of candidate genes for kidney disease pathogenesis. PMID- 27263489 TI - An overview of technical considerations for Western blotting applications to physiological research. AB - The applications of Western/immunoblotting (WB) techniques have reached multiple layers of the scientific community and are now considered routine procedures in the field of physiology. This is none more so than in relation to skeletal muscle physiology (i.e., resolving the mechanisms underpinning adaptations to exercise). Indeed, the inclusion of WB data is now considered an essential aspect of many such physiological publications to provide mechanistic insight into regulatory processes. Despite this popularity, and due to the ubiquitous and relatively inexpensive availability of WB equipment, the quality of WB in publications and subsequent analysis and interpretation of the data can be variable, perhaps resulting in spurious conclusions. This may be due to poor laboratory technique and/or lack of comprehension of the critical steps involved in WB and what quality control procedures should be in place to ensure robust data generation. The present review aims to provide a detailed description and critique of WB procedures and technicalities, from sample collection through preparation, blotting and detection, to analysis of the data collected. We aim to provide the reader with improved expertise to critically conduct, evaluate, and troubleshoot the WB process, to produce reproducible and reliable blots. PMID- 27263492 TI - Regulatory T cells in kidney disease and transplantation. AB - Regulatory T cells (Tregs) have been shown to be important in maintaining immune homeostasis and preventing autoimmune disease, including autoimmune kidney disease. It is also likely that they play a role in limiting kidney transplant rejection and potentially in promoting transplant tolerance. Although other subsets of Tregs exist, the most potent and well-defined Tregs are the Foxp3 expressing CD4(+) Tregs derived from the thymus or generated peripherally. These CD4(+)Foxp3(+) Tregs limit autoimmune renal disease in animal models, especially chronic kidney disease, and kidney transplantation. Furthermore, other subsets of Tregs, including CD8 Tregs, may play a role in immunosuppression in kidney disease. The development and protective mechanisms of Tregs in kidney disease and kidney transplantation involve multiple mechanisms of suppression. Here we review the development and function of CD4(+)Foxp3(+) Tregs. We discuss the specific application of Tregs as a therapeutic strategy to prevent kidney disease and to limit kidney transplant rejection and detail clinical trials in this area of transplantation. PMID- 27263493 TI - Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leukoplakia with dysplasia. AB - BACKGROUND: In the current study the presence of extracellular IL-1B, IL-8, OAZ and SAT mRNAs in the saliva was evaluated as a tool in the early detection of oral squamous cell carcinoma. METHODS: 34 patients with primary oral squamous cell carcinoma stage T1N0M0/T2N0M0, 20 patients with oral leukoplakia and dysplasia (15 patients with mild dysplasia and 5 with severe dysplasia/in situ carcinoma) and 31 matched healthy-control subjects were included in the study. The presence of IL-1B, IL-8, OAZ and SAT mRNA was evaluated in extracellular RNA isolated from saliva samples using sequence-specific primers and real-time RT PCR. ROC curve analysis was used to estimate the ability of the biomarkers to detect oral squamous cell carcinoma patients. RESULTS: The data reveal that the combination of these four biomarkers provides a good predictive probability of up to 80% (AUC=0.799, p=0.002) for patients with oral squamous cell carcinoma but not patients suffering from oral leukoplakia with dysplasia. Moreover, the combination of only the two biomarkers (SAT and IL-8) also raises a high predictive ability of 75.5% (AUC=0.755, p=0.007) approximately equal to the four biomarkers suggesting the use of the two biomarkers only in the prediction model for oral squamous cell carcinoma patients limiting the economic and health cost in half. CONCLUSION: SAT and IL-8 mRNAs are present in the saliva in high quality and quantity, with a good discriminatory ability for oral squamous cell carcinoma patients only but not for patients with oral leukoplakia and dysplasia an oral potentially malignant disorder. PMID- 27263494 TI - Microglial activation during epileptogenesis in a mouse model of tuberous sclerosis complex. AB - OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder, characterized by tumor formation in multiple organs and severe neurologic manifestations, including epilepsy, intellectual disability, and autism. Abnormalities of both neurons and astrocytes have been implicated in contributing to the neurologic phenotype of TSC, but the role of microglia in TSC has not been investigated. The objectives of this study were to characterize microglial activation in a mouse model of TSC, involving conditional inactivation of the Tsc1 gene predominantly in glial cells (Tsc1(GFAP) CKO mice), and to test the hypothesis that microglial activation contributes to epileptogenesis in this mouse model. METHODS: Microglial and astrocyte activation was examined in Tsc1(GFAP) CKO mice by ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein immunohistochemistry. Cytokine and chemokine expression was evaluated with quantitative polymerase chain reaction. Seizures were monitored by video electroencephalography (EEG). The effect of minocycline in inhibiting microglial and astrocyte activation, cytokine expression, and seizures was tested. RESULTS: Microglial cell number and size were increased in cortex and hippocampus of 3- to 4-week-old Tsc1(GFAP) CKO mice, which correlated with the onset of seizures. Minocycline treatment prevented the increase in number and cell size of microglia in 4-week-old Tsc1(GFAP) CKO mice. However, minocycline treatment had no effect on astrocyte proliferation and cytokine/chemokine expression and the progression of seizures in Tsc1(GFAP) CKO mice. SIGNIFICANCE: Microglia cell number and size are abnormal in Tsc1(GFAP) CKO mice, and minocycline treatment inhibits this microglia activation, but does not suppress seizures. Microglia may play a role in the neurologic manifestations of TSC, but additional studies are needed in other models and human studies to determine whether microglia are critical for epileptogenesis in TSC. PMID- 27263496 TI - Occupational differences in work engagement: A longitudinal study among eight occupational groups in Norway. AB - The aim of the present study was to explore occupational differences in the experience of engagement both with regard to differences in the level of work engagement as well as in the predicting value of different antecedent variables. Multigroup latent mean analysis was performed on eight different occupational groups in Norway (lawyers, physicians, nurses, teachers, church ministers, bus drivers, and people working in advertising and information technology; N = 3,475). Tests for factorial invariance supported the use of the Oldenburg Burnout Inventory scale across occupational groups and that the latent means were comparable across the groups. Results indicated significant occupational differences in the experience of vigor and dedication. The lawyers reported the most vigor and the church ministers the most dedication. Least vigor was reported among the teachers and the advertising group reported to be least dedicated. Cross-lagged multigroup structural equation modeling (SEM) analysis suggested there are different processes behind the development of engagement across occupations. Visualization of how some occupations cluster or differ from each other is important as it might engender theory building and further hypotheses testing. PMID- 27263495 TI - Quantifying promoter activity during the developmental cycle of Chlamydia trachomatis. AB - Chlamydia trachomatis is an important human pathogen that undergoes a characteristic development cycle correlating with stage-specific gene expression profiles. Taking advantage of recent developments in the genetic transformation in C. trachomatis, we constructed a versatile green fluorescent protein (GFP) reporter system to study the development-dependent function of C. trachomatis promoters in an attempt to elucidate the mechanism that controls C. trachomatis adaptability. We validated the use of the GFP reporter system by visualizing the activity of an early euo gene promoter. Additionally, we uncovered a new ompA promoter, which we named P3, utilizing the GFP reporter system combined with 5' rapid amplification of cDNA ends (RACE), in vitro transcription assays, real-time quantitative RT-PCR (RT-qPCR), and flow cytometry. Mutagenesis of the P3 region verifies that P3 is a new class of C. trachomatis sigma(66)-dependent promoter, which requires an extended -10 TGn motif for transcription. These results corroborate complex developmentally controlled ompA expression in C. trachomatis. The exploitation of genetically labeled C. trachomatis organisms with P3-driven GFP allows for the observation of changes in ompA expression in response to developmental signals. The results of this study could be used to complement previous findings and to advance understanding of C. trachomatis genetic expression. PMID- 27263498 TI - Efficient Z-scheme photocatalyst from simultaneous decoration of In2S3 nanosheets and WO3 nanorods on graphene sheets. AB - Inspired by natural photosynthesis, the Z-scheme photocatalyst is a promising approach to extend the absorption spectra of photocatalysts and reduce the recombination of photo-generated electrons and holes. However, the fabrication of well-structured efficient multi-component Z-scheme photocatalysts is still a big challenge. We report here a facile one-pot method to synthesize graphene-based Z scheme photocatalysts. The one-pot method guarantees good distribution of well structured individual components on thin-layered rGO sheets with excellent connections. With inactive WO3 nanorods and inactive beta-In2S3 nanosheets attached to the surface of the rGO sheets, the synthesized In2S3/WO3/rGO tertiary nanocomposite shows excellent visible-light catalytic activity for hydrogen production at 1524 MUmol g(-1) h(-1), demonstrating unambiguously the Z-scheme catalytic mechanism. To prevent cross-reactions and interferences, our strategy was to choose no more than one ionic precipitation reaction for the one-pot process, as unwanted cross-reactions could become inevitable if many cations and anions were present. This fabrication strategy should be applicable generally to synthesize other multiple-component nanocomposites, as demonstrated also by the preliminary results of the successful synthesis of the BiVO4/WO3/rGO nanocomposite (one ionic precipitation reaction and one hydrolysis reaction) and WO3/TiO2/rGO nanocomposite (two hydrolysis reactions). PMID- 27263497 TI - Determinants of resting cerebral blood flow in sickle cell disease. AB - Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated. This study examined the physiological determinants of CBF in 37 patients with sickle cell disease, 38 ethnicity matched control subjects and 16 patients with anemia of non sickle origin. Cerebral blood flow was measured using phase contrast MRI of the carotid and vertebral arteries. CBF increased inversely to oxygen content (r(2) = 0.69, P < 0.0001). Brain oxygen delivery, the product of CBF and oxygen content, was normal in all groups. Brain composition, specifically the relative amounts of grey and white matter, was the next strongest CBF predictor, presumably by influencing cerebral metabolic rate. Grey matter/white matter ratio and CBF declined monotonically until the age of 25 in all subjects, consistent with known maturational changes in brain composition. Further CBF reductions were observed with age in subjects older than 35 years of age, likely reflecting microvascular aging. On multivariate regression, CBF was independent of disease state, hemoglobin S, hemoglobin F, reticulocyte count and cell free hemoglobin, suggesting that it is regulated similarly in patients and control subjects. In conclusion, sickle cell disease patients had sufficient oxygen delivery at rest, but accomplish this only by marked increases in their resting CBF, potentially limiting their ability to further augment flow in response to stress. Am. J. Hematol. 91:912-917, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27263499 TI - A remote monitoring program evaluation: a retrospective study. AB - OBJECTIVE: Using an integrated model, the Donabedian Quality and Logic Model, we examined a remote monitoring heart failure disease management program. METHOD: This quantitative research used post-test only case matched design. The sample consisted of 210 participants from 23 home health care agencies. RESULTS: Logistic regression results indicated statistical significance, there was an inverse relationship between caregiver support and the complexity of decision making; X2 (3, n = 210) = 29.984, P = 0.012. The DTreg suggested that participants who were advised to go to the ER had a 1.00 probability of doing so, and those who were instructed otherwise had a 0.37 probability of going to the ER. Among participants who experienced a hospital readmission, there was 0.50 probability that patient education or other clinical intervention was implemented prior to the admission. CONCLUSION: As home health care agencies consider disease management programs, it is important to gain a comprehensive understanding of the potential of innovative programs and the resources they require. While the agency invested the resources required by the remote monitoring program, the study demonstrated that caregiver support was a critical structural component of the program and may affect change in nurses' decision making to mitigate hospital utilization. We recommend that home health care agencies take greater consideration of the family and social support in implementing a remote monitoring system. PMID- 27263500 TI - Immunosuppressive Therapy-Induced Hepatotoxicity in Patients with Aplastic Anemia. AB - Immunosuppressive therapy is a treatment for aplastic anemia patients who are not candidates for hematopoietic stem cell transplantation. The aim of the study to evaluate the frequency and severity of immunosuppressive therapy-induced hepatotoxicity in patients with aplastic anemia. The records of 27 patients with aplastic anemia who had eceived immunosuppressive therapy were received and determined for evidence of hepatotoxicity. The patients were divided into three groups. Group 1 was treated with antithymocyte/antilymphocyte globulin and cyclosporin A, group 2 received onl yyclosporin-A and group 3 was treated with antithymocyte/antilymphocyte globulin + cyclosporin-A and granulocyte macrophage colony-stimulating factor. All patients in group 1 had an initial increase in AST and ALT levels after therapy, but these tests abnormalities returned to normal in each case (p> 0.05). There was no detectable change in AST and ALT levels in group 2 (p>0.05). In group 3, five patients had an increase in ALT and AST levels in the initial several days after therapy was started but he levels gradually returnedto normal by the second or third week of therapy. PMID- 27263501 TI - Natural Inhibitors and Lipids in Patients with Sickle Cell Disease. AB - Microvascular occlusion in sickle cell disease (SCD) is a multifactorial process. Disordered coagulation may play a role in the pathogenesis of vaso occlusive crisis (VOC). The aim of this study was to evaluate the patients and to investigate their Protein C (PC), Protein S (PS) and AT-III levels during normal and crisis periods. A total of 18 patients with SCD were included in this study at the Antalya State Hospital, Thalassemia Center. The mean number of VOC episodes of the patients per year was 4.1 - 3.2. Complications in patients included 4 cases of osteonecrosis (23.5%), 2 cases of holealithiasis (11.7%), 2 cases of leg ulcers (11.7%), and 3 splenectomies (17.6%). The patients during noncrisis periods have lower cholesterol and higher triglycerides levels than the controls (p< 0.001). Hepatic and renal functions were normal in all patients. The mean totals of the PS, PC and AT-III levels were statistically lower both in non crisis and in crisis periods than the control (p< 0.001), but there was no statistical difference between the levels durining noncrisis and crisis periods. In conclusion, PC, PS and AT-IIII deficiencies in patients with SCD are certain. However, these deficiencies do not change during noncrisis and crisis situations and does not play a role on the period of crisis. Abnormal lipid patterns may be a predisposing condition for a crisis. PMID- 27263502 TI - Hematological Values of Healthy Adult Population Living at Moderate Altitude (1869 m, Erzurum, Turkey). AB - In this study, the normal hematological values in healthy adults living in Erzurum area in Turkey at moderate altitude (1869 m above sea level), and the effect of moderate altitude on these hematological values was investigated. The study population comprised of 929 females and 1204 males aged between 17-95. The mean values for red blood cell and leukocyte counts, and hemoglobin level were significantly higher in males than in females (p<0.0001), whereas platelet count was significantly higher in females than in males (p<0.0001). >n conclusion, we could not find an increase in the number of red blood cells as well as other hematological parameters in healthy adults living in Erzurum area. Hematological values in this study were similar to those reported in the previous studies carried out with those living under 1869 m. PMID- 27263503 TI - Ticlopidine Induced Anemia and Agranulocytosis. AB - A 63-year-old man with a history of transient ischemic attack had been treated with ticlopidine for 2 months. He presented with a 6-day history of fever, sore throat, and generalized weakness. Agranulocytosis and anemia due to ticlopidine was diagnosed, and the ticlopidine was discontinued. Broad-spectrum antibiotics and granulocyte colony stimulating factor were administered. The recovery of the granulocyte count and an improvement of the clinical condition were noted on the 6th day of the admission. PMID- 27263504 TI - Multiple Cerebral Emboli in a Homozygous b-Thalassaemia Patient Due to Factor V 1299 (His-Arg) 4070 A-G Mutation. AB - Thromboembolic episodes are quite rare in beta thalassemia major patients although there is a tendency for thrombosis in haemolytic anaemias. We report a patient with cerebral thromboembolic episode triggered by a minor blood group incompatibility in which the underlying defect of factor V 1299 (His-Arg) was detected three years after his death. PMID- 27263505 TI - Could Parvovirus B19 Induce a Rejection After Bone Marrow Transplantation in a Patient with Diamond-Blackfan Anemia? AB - A four year-old-girl with Diamond-Blackfan anemia (DBA) that was resistant to corticosteroid treatment and transfusion dependent underwent (bone marrow transplantation) BMT from HLA identical sibling. The patient was conditioned with busulfan and cyclophosphamide and achieved complete marrow engraftment and mixed chimerism in DNA analysis. For the following 13 months she was not transfusion dependent and had a 100% Karnofsky score. But on the 14th month she had anemia ollowing fever, rash and enteritis. Parvovirus B19 IgM seropositivity confirmed Parvovirus infection. Although intravenous immunoglobulin was administered, bone marrow morphology and DNA analysis revealed rejection. Although mixed chimerism detected shortly after the BMT procedure might raise the possibility of an ongoing slow graft rejection during the relatively stable remission period, we think that parvovirus B19 had also contributed rejection. PMID- 27263506 TI - Images in Haematology. PMID- 27263507 TI - Cultural influences on neural basis of inhibitory control. AB - Research on neural basis of inhibitory control has been extensively conducted in various parts of the world. It is often implicitly assumed that neural basis of inhibitory control is universally similar across cultures. Here, we investigated the extent to which culture modulated inhibitory-control brain activity at both cultural-group and cultural-value levels of analysis. During fMRI scanning, participants from different cultural groups (including Caucasian-Americans and Japanese-Americans living in the United States and native Japanese living in Japan) performed a Go/No-Go task. They also completed behavioral surveys assessing cultural values of behavioral consistency, or the extent to which one's behaviors in daily life are consistent across situations. Across participants, the Go/No-Go task elicited stronger neural activity in several inhibitory-control areas, such as the inferior frontal gyrus (IFG) and anterior cingulate cortex (ACC). Importantly, at the cultural-group level, we found variation in left IFG (L-IFG) activity that was explained by a cultural region where participants lived in (as opposed to race). Specifically, L-IFG activity was stronger for native Japanese compared to Caucasian- and Japanese-Americans, while there was no systematic difference in L-IFG activity between Japanese- and Caucasian Americans. At the cultural-value level, we found that participants who valued being "themselves" across situations (i.e., having high endorsement of behavioral consistency) elicited stronger rostral ACC activity during the Go/No-Go task. Altogether, our findings provide novel insight into how culture modulates the neural basis of inhibitory control. PMID- 27263508 TI - Predictability of what or where reduces brain activity, but a bottleneck occurs when both are predictable. AB - Detecting regularities in the sensory environment licenses predictions that enable adaptive behaviour. However, it is unclear whether predictions about object category, location, or both dimensions are mediated by overlapping systems, and relatedly, whether constructing predictions about both category and location is associated with processing bottlenecks. To examine this issue, in an fMRI study, we presented participants with image-series in which non deterministic transition probabilities enabled predictions about either the location of the next image, its semantic category, both dimensions, or neither (the latter forming a "no-regularity" random baseline condition). Speaking to a common system, all three predictable conditions resulted in reduced BOLD activity in four clusters: left rostral anterior cingulate cortex; bilateral putamen, caudate and thalamus; right precentral gyrus, and left visual cortex. Pointing to a processing bottleneck, in some regions, a significant interaction between the two factors was found whereby category-predictable series were associated with lower activity - but only when location regularity was absent. Finally, category regularity decreased activation in areas of the ventral visual stream and semantic areas of lateral temporal cortex, and location regularity decreased activation in a dorsal fronto-parietal cluster, long implicated in the endogenous control of spatial attention. Our findings confirm and expand a role for dACC/dmPFC and striatum in monitoring or responding to uncertainty in the environment and point to a limited capacity bottleneck when multiple predictions are concurrently licensed. PMID- 27263510 TI - The extended human PTPome: a growing tyrosine phosphatase family. PMID- 27263513 TI - Robot-assisted spleen preserving pancreatic surgery in MEN1 patients. AB - BACKGROUND: Multiple Endocrine Neoplasia type 1 (MEN1) patients often undergo multiple pancreatic operations at a young age. OBJECTIVE: To describe robot assisted and laparoscopic spleen-preserving pancreatic surgery in MEN1 patients, and to compare both techniques. METHODS: Robot-assisted pancreatectomies of the DutchMEN1 study group and the Universite de Lorraine, Nancy, France were compared to a historical cohort of laparoscopic treated MEN1 patients. Perioperative outcomes were compared. RESULTS: A total of 21 MEN1 patients underwent minimally invasive pancreatic surgery for pancreatic neuroendocrine tumors, seven patients were subjected to robot-assisted surgery, and 14 patients underwent laparoscopic surgery. Demographics and clinical characteristics did not differ between the cohorts and no significant differences in operative outcomes were found. A high number of ISGPS grade B/C pancreatic fistulas were observed in both cohorts (38%), and no conversions were seen in the robot-assisted cohort (respectively 0% vs. 43%, P = 0.06). In one laparoscopic and one robot-assisted case the primary tumor was not resected. CONCLUSIONS: Minimally invasive spleen-preserving surgery in MEN1 patients is safe and feasible. Patients who underwent robot-assisted surgery did not require conversion to open surgery. J. Surg. Oncol. 2016;114:456 461. (c) 2016 Wiley Periodicals, Inc. PMID- 27263515 TI - Nuclear Medicine Applications in Hemato-Oncology. PMID- 27263514 TI - Synthesis and structures of stable phosphorus zwitterions derived from mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates. AB - Trialkyl phosphites were evaluated as phosphorus nucleophiles for addition to mesoionic 4-trifluoroacetyl-1,3-oxazolium-5-olates (1), thereby producing tetravalent phosphorus zwitterions (2) in good yields. The structure of 2 was determined to be a tetravalent phosphonium enolate via single crystal X-ray analysis. PMID- 27263512 TI - Single-room usage patterns and allocation decision-making in an Australian public hospital: a sequential exploratory study. AB - AIMS AND OBJECTIVES: The aims are to (1) measure occupancy rates of single and shared rooms; (2) compare single room usage patterns and (3) explore the practice, rationale and decision-making processes associated with single rooms; across one Australian public health service. BACKGROUND: There is a tendency in Australia and internationally to increase the proportion of single patient rooms in hospitals. To date there have been no Australian studies that investigate the use of single rooms in clinical practice. DESIGN: This study used a sequential exploratory design with data collected in 2014. METHODS: A descriptive survey was used to measure the use of single rooms across a two-week time frame. Semi structured interviews were undertaken with occupancy decision-makers to explore the practices, rationale decision-making process associated with single-room allocation. RESULTS: Total bed occupancy did not fall below 99.4% during the period of data collection. Infection control was the primary reason for patients to be allocated to a single room, however, the patterns varied according to ward type and single-room availability. For occupancy decision-makers, decisions about patient allocation was a complex and challenging process, influenced and complicated by numerous factors including occupancy rates, the infection status of the patient/s, funding and patient/family preference. Bed moves were common resulting from frequent re-evaluation of need. CONCLUSION: Apart from infection control mandates, there was little tangible evidence to guide decision-making about single-room allocation. Further work is necessary to assist nurses in their decision-making. RELEVANCE TO CLINICAL PRACTICE: There is a trend towards increasing the proportion of single rooms in new hospital builds. Coupled with the competing clinical demands for single room care, this study highlights the complexity of nursing decision-making about patient allocation to single rooms, an issue urgently requiring further attention. PMID- 27263516 TI - Homozygosity for the HR2 Haplotype: Is It a Risk Factor for Thrombosis? AB - A4070G (His 1299 Arg) polymorphism in exon 13 of factor V gene can influence factor V levels and contribute to the activated protein C resistance. We are presenting our data concerning Turkish population and postulate that homozygosity for the HR2 haplotype may be an important risk factor for thrombosis. PMID- 27263509 TI - Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal consecutive stages of motivated attention. AB - Event-related potential (ERP) studies have provided evidence for an allocation of attentional resources to enhance perceptual processing of motivationally salient stimuli. Emotional modulation affects several consecutive components associated with stages of affective-cognitive processing, beginning as early as 100-200ms after stimulus onset. In agreement with the notion that the right parietotemporal region is critically involved during the perception of arousing affective stimuli, some ERP studies have reported asymmetric emotional ERP effects. However, it is difficult to separate emotional from non-emotional effects because differences in stimulus content unrelated to affective salience or task demands may also be associated with lateralized function or promote cognitive processing. Other concerns pertain to the operational definition and statistical independence of ERP component measures, their dependence on an EEG reference, and spatial smearing due to volume conduction, all of which impede the identification of distinct scalp activation patterns associated with affective processing. Building on prior research using a visual half-field paradigm with highly controlled emotional stimuli (pictures of cosmetic surgery patients showing disordered [negative] or healed [neutral] facial areas before or after treatment), 72 channel ERPs recorded from 152 individuals (ages 13-68years; 81 female) were transformed into reference-free current source density (CSD) waveforms and submitted to temporal principal components analysis (PCA) to identify their underlying neuronal generator patterns. Using both nonparametric randomization tests and repeated measures ANOVA, robust effects of emotional content were found over parietooccipital regions for CSD factors corresponding to N2 sink (212ms peak latency), P3 source (385ms) and a late centroparietal source (630ms), all indicative of greater positivity for negative than neutral stimuli. For the N2 sink, emotional effects were right-lateralized and modulated by hemifield, with larger amplitude and asymmetry for left hemifield (right hemisphere) presentations. For all three factors, more positive amplitudes at parietooccipital sites were associated with increased ratings of negative valence and greater arousal. Distributed inverse solutions of the CSD-PCA-based emotional effects implicated a sequence of maximal activations in right occipitotemporal cortex, bilateral posterior cingulate cortex, and bilateral inferior temporal cortex. These findings are consistent with hierarchical activations of the ventral visual pathway reflecting subsequent processing stages in response to motivationally salient stimuli. PMID- 27263517 TI - 1,25(OH)2D3 incubation up-Regulates HOX A9 gene in HL-60 cells. AB - There are many genes involved in vitamin D dependent differentiation of acute myeloid leukaemia cell line HL-60 cells. Involvement of HOX genes in leukaemia and differentiation is just beginning to be appreciated. In order to understand the relationship with 1,25(OH)2D3 dependent differentiation of myeloid leukaemia, we studied the expression of HOX A9 gene. HL-60 cells were exposed to 1,25(OH)2D3 for 24 and 72 hours. Gene expression were investigated using quantitative real time RT-PCR (LightCycler). HOX A9 levels were found upregulated after 1,25(OH)2D3 treatment, compared to housekeeping RPS9 and HPRT genes. Our study is the first attempt to quantification of HOX A9 gene during 1,25(OH)2D3 treatment, using this technology. We suggest that there is a clear relationship between differentiation induction and over-expression of HOX A9 gene in HL-60 cells. Possible correlation of high expression levels of HOX A9 gene in AML pathogenesis remains to be established. PMID- 27263518 TI - R506Q (FV Leiden) and R485K Mutations in the Factor V Gene: Incidence in Deep Venous Thrombosis and Hemophilia A Patients. AB - R506Q (FV Leiden) mutation in exon 10 of the factor V (FV) gene is highly prevalent in European populations and it has been suggested that the coinheritance of FV Leiden mutation may be an important modifier of hemophilia A phenotype. One other substitution R485K in the same exon, with no functional consequences in vitro, is significantly higher in Thailand and has been associated with thrombophilia. In order to see if any correlation exists between R506Q and hemophilia phenotype and between R485K and thrombosis in Turkish patients, DGGE analysis of exon 10 of the FV gene is carried out among deep venous thrombosis (DVT) and hemophilia A patients. Our results indicate that the allelic frequency of the R485K polymorphism is similar to the frequency detected in Europe, and apparently, is not associated with an increased risk of thrombosis in the Turkish population. It is also not possible to show a modifier effect of FV Leiden on hemophilia A phenotype among the limited number of patients included in this study. PMID- 27263519 TI - Microorganisms Isolated from Blood Cultures of Febrile Neutropenic Patients in =5 on the Clinical Frailty Scale before hospitalization. Multivariable analyses were used to evaluate factors independently associated with frailty before ICU admission and the independent association between frailty and outcome. RESULTS: In the 197 patients in the study, mean (SD) age was 58.5 (4.1) years, 37 % were female, 73 % had three or more comorbid illnesses, and 28 % (n = 55; 95 % CI 22-35) were frail. Factors independently associated with frailty included not being completely independent (adjusted OR [aOR] 4.4, 95 % CI 1.8-11.1), connective tissue disease (aOR 6.0, 95 % CI 2.1-17.0), and hospitalization within the preceding year (aOR 3.3, 95 % CI 1.3-8.1). There were no significant differences between frail and nonfrail patients in reason for admission, Acute Physiology and Chronic Health Evaluation II score, preference for life support, or treatment intensity. Younger frail patients did not have significantly longer (median [interquartile range]) hospital stay (26 [9-68] days vs. 19 [10-43] days; p = 0.4), but they had greater 1-year rehospitalization rates (61 % vs. 40 %; p = 0.02) and higher 1-year mortality (33 % vs. 20 %; adjusted HR 1.8, 95 % CI 1.0-3.3; p = 0.039). CONCLUSIONS: Prehospital frailty is common among younger critically ill patients, and in this study it was associated with higher rates of mortality at 1 year and with rehospitalization. Our data suggest that frailty should be considered in younger adults admitted to the ICU, not just in the elderly. Additional research is needed to further characterize frailty in younger critically ill patients, along with the ideal instruments for identification. PMID- 27263536 TI - Post Pelvic Radiotherapy Affectation of the Lower Urinary Tract Peripheral Innervation in Men. AB - INTRODUCTION: The periurethral electromyography (EMGs) alterations in men who underwent pelvic radiotherapy (RT), either isolated or combined with surgery, have not been frequently described in the literature. OBJECTIVE: The study aimed to compare the EMG's data in men undergoing RT versus the non-irradiated control group. MATERIAL AND METHODS: The study included 61 consecutive males, who had undergone RT (27 of them had been operated) and 99 control consecutive patients who underwent a retrospective assessment. The EMGs were performed using a concentric electrode needle perineally, localizing the sphincter by visual and auditory signal (electromyograph MMS Solar Active). RESULTS: 14.8% denervation, 62.9% reinnervation, 14.9% denervation + reinnervation and 7.4% EMG normal. The age (p < 0.001) and neurogenic bladder data (p < 0.001) are risk factors. The smaller the prostate size (obtained by rectal examination) post-RT, the more the chance for an abnormal EMG (p < 0.001). The fact of having had received RT (p < 0.001) is the only risk factor. CONCLUSION: RT produces lesions over the pudendal nerve, showing denervation even in late periods. The surgery did not behave as a risk factor. PMID- 27263537 TI - Changes in the Serum Levels of Trace Elements Before and After the Operation in Thyroid Cancer Patients. AB - The present study aims to examine the changes in the serum levels of trace elements before and after the operation in thyroid cancer patients. The study registered 50 individuals, of whom 25 were female and 25 were male. The patients were allocated to four groups: group 1: male thyroid cancer patients group (n = 15), group 2: female thyroid cancer patients group (n = 15), group 3: male control group (n = 10), group 4: female control group (n = 10). The subjects in groups 1 and 2 were the patients who were post-operatively diagnosed with a pathological malignancy in the thyroid tissue samples. Blood samples were collected from all subjects before the operation, immediately after the operation, and on the post-operative day 15. Additionally, thyroid tissue samples were taken from all subjects post-operatively. Some elements in the blood and tissue samples were determined using the atomic emission method. Zinc and selenium levels of groups 1 and 2 in the pre- and post-operative measurements were significantly lower than those in the control groups (p < 0.05), but were higher in the thyroid tissue (p < 0.05). Serum zinc and selenium levels measured in the subjects on the post-operative day 15 were similar to those measured in the controls. Our study show that changes in the serum and thyroid tissue levels of trace elements like zinc and selenium, which play a critical role in thyroid function, might be associated with the pathogenesis of thyroid cancer. PMID- 27263538 TI - Reliability and Validity of Two Measures of Toileting Skills in Frail Older Women Without Dementia. AB - Urinary incontinence (UI) affects 43% of frail, community-dwelling older women and threatens their independence. For these women, remaining continent depends on their ability to toilet. Treatments should include improving toileting skills. However, reliable and valid measures of toileting skills are not available to evaluate treatment efforts in this population. The current cross-sectional study of 24 frail older women (average age = 87 years) examines the reliability and concurrent validity of the Performance Oriented Timed Toileting Instrument (POTTI) and self-reported Minnesota Toileting Skills Questionnaire (MTSQ). The POTTI demonstrated strong interrater reliability (0.97) and the MTSQ demonstrated good internal consistency (Cronbach;s alpha = 0.82). Both measures had statistically significant correlations with frailty, physical performance, UI related quality of life, and UI self-efficacy. Both instruments demonstrated good psychometric properties and show promise as outcome measures for UI clinical trials. Further work is needed to establish their responsiveness to change and minimum clinically important difference values. [Journal of Gerontological Nursing, xx(x), xx-xx.]. PMID- 27263539 TI - A Client-Centered Community Engagement Project: Improving the Health and Wellness of Older Adults in an Assisted Living Facility. AB - Central to nursing practice is the promotion of health and wellness practices. Drawing on the Community as Partner Model, nursing process, Nursing Interventions Classification, and Logic Model, second-year nursing students collaborated with staff and residents of an assisted living facility to promote health and wellness in the older adult population. Windshield surveys, resident surveys, key informant interviews, and focus group interviews were conducted to gain insight into the perceptions and experiences of staff and residents. The majority of residents indicated they were satisfied with life at the facility and their needs have been adequately met. Strengths and areas for improvement were identified in several aspects, including the facility atmosphere and location, quality of staff and health care services, recreational and dietary services, and social support networks. By partnering with community key stakeholders, valuing all different perspectives, and connecting theory to practice, a successful client-centered community clinical project was demonstrated. [Journal of Gerontological Nursing, 42(8), 44-51.]. PMID- 27263540 TI - Honoring Individual Choice in Long-Term Residential Communities When It Involves Risk: A Person-Centered Approach. AB - Nursing homes that are working on adopting person-centered care (PCC) practices express concerns about giving residents the freedom to make their own decisions and the accompanying risks. This challenge is especially true for those who are at the beginning of the PCC change process. Although the Centers for Medicare and Medicaid Services regulations are clear that residents have the right to a dignified existence and self-determination, and that the facility must protect and promote their rights, examples abound of care communities coercing, cajoling, or requiring residents to do things they do not want to do (e.g., take medications), or the reverse of not letting them do what they want (e.g., eat a regular diet). The current article discusses a process that helps care communities follow the regulations about education and offering choices while honoring resident preferences and documenting the process for surveyors. [Journal of Gerontological Nursing, 42(8), 12-17.]. PMID- 27263541 TI - Quantitative Subsurface Atomic Structure Fingerprint for 2D Materials and Heterostructures by First-Principles-Calibrated Contact-Resonance Atomic Force Microscopy. AB - Interfaces and subsurface layers are critical for the performance of devices made of 2D materials and heterostructures. Facile, nondestructive, and quantitative ways to characterize the structure of atomically thin, layered materials are thus essential to ensure control of the resultant properties. Here, we show that contact-resonance atomic force microscopy-which is exquisitely sensitive to stiffness changes that arise from even a single atomic layer of a van der Waals adhered material-is a powerful experimental tool to address this challenge. A combined density functional theory and continuum modeling approach is introduced that yields sub-surface-sensitive, nanomechanical fingerprints associated with specific, well-defined structure models of individual surface domains. Where such models are known, this information can be correlated with experimentally obtained contact-resonance frequency maps to reveal the (sub)surface structure of different domains on the sample. PMID- 27263542 TI - Revitalizing the Frens Method To Synthesize Uniform, Quasi-Spherical Gold Nanoparticles with Deliberately Regulated Sizes from 2 to 330 nm. AB - In this work, we have successfully developed a new and consistent model to describe the growth of gold nanoparticles (Au NPs) via citrate reduction of auric acid (HAuCl4) by carefully assessing the temporal evolution of the NP sizes and surface charges by means of dynamic light scattering (DLS) and zeta-potential measurements. The new model demonstrates that the nucleation and growth of the Au NPs occur exclusively in the particles of the complexes of Au(+) ions and sodium acetone dicarboxylate (SAD) derived from the citrate/HAuCl4 redox reaction, which proceeds as described by the classic LaMer model. Concomitant with the Au NP growing therein, the Au(+)/SAD complex particles undergo reversible agglomeration with the reaction time, which may result in an abnormal color change of the reaction media but have little impact on the Au NP growth. Built on the new model, we have successfully produced monodisperse quasi-spherical Au NPs with sizes precisely regulated from 2 to 330 nm via simple citrate reduction in a one pot manner. To date, highly uniform Au NPs with sizes spanning such a large size range could not be formed otherwise even via deliberately controlled seeded growth methods. PMID- 27263543 TI - Characterization of the Key Odorants in Chinese Zhima Aroma-Type Baijiu by Gas Chromatography-Olfactometry, Quantitative Measurements, Aroma Recombination, and Omission Studies. AB - Zhima aroma-type Baijiu with typical sesame aroma is particularly popular in northern China. To our knowledge, it is still uncertain which components are important to make contributions to its unique aroma, although a few pieces of research have reported many volatile compounds in this Baijiu. The aroma-active compounds from the Baijiu were researched in this paper. A total of 56 odorants were identified in Chinese Zhima aroma-type Baijiu by aroma extract dilution analysis (AEDA). Their odor activity values (OAVs) were determined by different quantitative measurements, and then 26 aroma compounds were further confirmed as important odorants due to their OAVs >= 1, and these had higher values, such as ethyl hexanoate (OAV 2691), 3-methylbutanal (2403), ethyl pentanoate (1019), and so on. The overall aroma of Zhima aroma-type Baijiu could be simulated by mixing of the 26 key odorants in their measured concentrations. The similarity of the overall aroma profiles between the recombination model and the commercial sample was judged to be 2.7 out of 3.0 points. Omission experiments further corroborated the importance of methional and ethyl hexanoate for the overall aroma of Chinese Zhima aroma-type Baijiu. PMID- 27263544 TI - Ruxolitinib - better prognostic impact in low-intermediate 1 risk score: evaluation of the 'rete ematologica pugliese' (REP) in primary and secondary myelofibrosis. AB - We evaluated ruxolitinib in 65 patients with myelofibrosis according to age, sex, time of diagnosis, grade of fibrosis, prognostic score risk, Janus kinase (JAK) status, primary or secondary myelofibrosis, previous treatment, and dosage. Outcome measures were response rate, time to response, duration of response, and event-free survival and survival. Kaplan and Meier curves show a significant difference in event-free survival according to the prognostic score, in favor of patients with low int1 (p = 0.0009). The Cox stepwise model confirmed the result, the int2 high-risk score being the most powerful negative independent parameter (0.001), followed by JAK (0.008); other parameters, such as diagnosis more than 5 years earlier, grade III-IV fibrosis, and ruxolitinib dose have a negligible impact. Time to response was shorter (p = 0.001) in primary myelofibrosis. In conclusion, ruxolitinib is effective, with a better outcome in patients with a low-int1 risk score. This may suggest considering an earlier administration in the disease course. PMID- 27263545 TI - Application of arteether-loaded polyurethane nanomicelles to induce immune response in breast cancer model. AB - To concentrate a potent anticancer drug (Arteether) in tumor microenvironment, we encapsulated it in biodegradable and pH sensitive polyurethane (PU) nanomicelles (NMs). The nanocomplex was characterized by Fourier transform infrared (FTIR), dynamic light scattering (DLS). The loading capacity and release profile in pH of 5.4 and 7.4 were considered. The cytotoxicity effect was evaluated in vitro and in vivo settings. The level of IFN-gamma and IL-4 cytokines of mice splenocytes were assessed by enzyme-linked immunosorbent assay (ELISA). The nanocomplex showed negative zeta charge of -26.2 mV, size of 42.30 nm and high loading capacity (92%). Release profile showed a faster rate of drug liberation at pH 5.4 as compared to that of pH 7.4. It indicated significant inhibitory effect on the growth of 4T1 cell line and increased IFN-gamma level. PMID- 27263597 TI - Iron transport: From enterocyte to mitochondria. AB - Transport of iron to tissues is of vital importance. Remarkable advances have been made concerning the mechanisms involving iron metabolism after its absorption. Studies assessing cellular and mitochondrial iron metabolism have resulted in interesting findings. This review highlights the recent advances in the mechanisms involving transport and delivery of iron to tissues, cellular and mitochondrial iron metabolism, iron-related molecules, and mitochondrial disorders. PMID- 27263598 TI - Variant clinical courses in children with immune thrombocytopenic purpura: Sixteen year experience of a single medical center. AB - OBJECTIVE: Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia in children. The objective of this study was to evaluate the presenting features, variation in the clinical courses, initial response rate to therapy, and long-term outcome in patients with ITP. METHODS: Three hundred and fifty out of 491 newly diagnosed patients with ITP between the initial diagnosis ages of 6 months to 16 years were included in this retrospective, descriptive study. Patients with acute vs chronic ITP, acute vs recurrent ITP and chronic vs recurrent ITP were compared in terms of age at diagnosis, gender, initial platelet count, response rate to initial therapy, long term outcome, and total duration of follow-up. RESULTS: The clinical courses of the patients were determined as acute, chronic and recurrent in 63.8%, 29.1%, and 7.1%, respectively. Platelet count >20x109/L and initial diagnosis age >10 years were found to increase the probability of chronic outcome by at least two-fold. CONCLUSION: It is concluded that ITP in childhood is a common disease with low morbidity and mortality. In addition to the acute and chronic form, a rare recurrent form, which accounts for about 4-7% of all ITP patients, should be considered. PMID- 27263546 TI - Association of financial and health literacy with cognitive health in old age. AB - We tested the hypothesis that higher financial and health literacy is associated with better cognitive health in 755 older persons who completed a literacy measure (M = 67.9, SD = 14.5) and then had annual clinical evaluations for a mean of 3.4 years. In proportional hazards models, higher literacy was associated with decreased risk of developing incident Alzheimer's disease (n = 68) and results were similar for financial and health literacy subscales and after adjustment for potential confounders. In mixed-effects models, higher literacy was related to higher baseline level of cognition and reduced cognitive decline in multiple domains. Among the 602 persons without any cognitive impairment at baseline, higher literacy was associated with a reduced rate of cognitive decline and risk of developing incident mild cognitive impairment (n = 142). The results suggest that higher levels of financial and health literacy are associated with maintenance of cognitive health in old age. PMID- 27263599 TI - Efficacy of immunization against hepatitis B virus infection in acute leukemia. AB - OBJECTIVE: The aim of this study was to assess the antibody response to combined passive-active immunization versus active immunization against hepatitis B in 71 patients with acute leukemia with negative hepatitis B virus serology at presentation. METHODS: The first group (n=28) received a double dose of hepatitis B vaccine at 0, 1, 2 and 6 months and immunoglobin (HBIG) at 0 and 1 month concurrently with vaccine but at a different intramuscular site. The second group (n=43) received double dose of hepatitis B vaccine at 0, 1, 2, and 6 months. HBsAg and anti-HBs titers were determined one month after the 1st, 2nd, 3rd and 4th doses of vaccine. ESULTS: In the vaccine-only group, 2.56%, 8.33%, 14.28% and 34.29% of patients developed anti-HBs titer >=10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. In the HBIG group, 91.30%, 91.30%, 69.56% and 73.91% of patients developed anti-HBs titer >=10 IU/L after the 1st, 2nd, 3rd and 4th doses of vaccine, respectively. Those in the vaccine-HBIG group maintained their anti-HBs titer >=10 IU/L from the 1st to the 4th doses. In the vaccine-only group, 34.29% of patients gained protective antibody titer after receiving the 4th dose of vaccine. Subgroup analysis of age (pediatric vs adult) and disease (acute lymphoblastic leukemia vs acute myeloid leukemia) groups showed no effect of either on the development of protective antibody titer. The incidence of HBsAg positivity one month after the 4th dose of vaccine was 8.62%. No patient became positive for anti-HCV or HIV antibody before or after chemo therapy. CONCLUSION: Combined HBIG and vaccine may protect acute leukemia patients during the intensive chemotherapy period. PMID- 27263600 TI - Evaluation of risk factors for thrombophilia in patients with cerebral venous thrombosis. AB - OBJECTIVE: The increased risk for thrombosis is known as hypercoagulability or thrombophilia. In our study, we aimed to compare the frequency of the identified defects for thrombophilia in patients with central venous thrombosis and under the age of 50 years, with the findings in the current literature. METHODS: Forty three patients (16-50 years old) were retrospectively evaluated. Thrombophilia investigation included determinations of protein C, protein S, antithrombin, and activated protein C resistance, factor V Leiden (FVL), prothrombin 20210A (PT 20210) and methylene tetrahydrofolate reductase (MTHFR) C677T mutations, antiphospholipid antibodies (APA), factor VIII levels, and homocysteine levels. RESULTS: We detected a single thrombophilic defect in 67.4%, two defects in 27.9% and three defects in 4.7% of our patients. The most common thrombophilic defect was mutation in the MTHFR gene (41.8%), and this was followed by the FVL mutation (34.9%). CONCLUSION: Since the prevalence of individual thrombophilic defects varies in each population, ethnic group and geographical location, screening for thrombophilic defects in patients presenting with cerebral venous thrombosis should primarily investigate the most frequent thrombophilia risk factors. PMID- 27263601 TI - Posterior reversible leukoencephalopathy syndrome in children with hematologic disorders. AB - OBJECTIVE: Posterior reversible leukoencephalopathy syndrome (PRES) is characterized by headache, altered mental status, cortical blindness, and seizures associated with neuroradiological findings. It involves predominantly white matter of the parieto-occipital lobes. Several medications and disorders play a role in the etiology of PRES. In this study, we aimed to show how the prognosis of PRES in hematological diseases of childhood might be according to the etiological factors. METHODS: Here, we report PRES in six patients, aged 4 to 14 years, with diagnoses of leukemia and aplastic anemia. RESULTS: Suggested causes in our patients were chemotherapeutics, hypertension, infection and antimicrobial drug administration, tumor lysis syndrome, acute renal failure and hemodialysis, immunosuppressive drug administration, and hypomagnesemia. One of the patients died of sepsis, renal failure and pulmonary hemorrhage and another died of relapse after total recovery from PRES. The other four patients are under follow-up without problems. CONCLUSION: We suggest that PRES can recover fully with early diagnosis and treatment whereas it can show poor prognosis depending on the etiology. PMID- 27263602 TI - The effect of calabash chalk on some hematological parameters in female adult Wistar rats. AB - OBJECTIVE: Calabash chalk is a naturally occurring mineral consumed among the Nigerian community for pleasure and commonly by pregnant women as a remedy for morning sickness. Reports have shown that it contains different toxic substances, with lead being the most abundant. This study was therefore undertaken to ascertain the effect of two commonly available preparations of this chalk on some hematological parameters. METHODS: Twenty-four adult female Wistar rats with average weight of 100 g were assigned into three groups (1, 2, 3). Group 1 served as the control and the animals received distilled water, while Groups 2 and 3 were treated by oral gavage with 40 mg/kg of non-salted (NSCC) and salted calabash chalk (SCC), respectively, for 14 days. RESULTS: The hemoglobin (Hb) concentration and red blood cell (RBC) count were significantly (p<0.05, 0.001 respectively) lower in the NSCC group, while erythrocyte sedimentation rate (ESR) was significantly (p<0.05) higher in the NSCC group compared to the control. There were no significant differences in packed cell volume (PCV), white blood cell (WBC) and platelet (Pl) counts compared to the control. The SCC group presented no significant difference in all blood count parameters compared to the control. CONCLUSION: This infers that calabash chalk, particularly the non-salted form, alters the normal concentration of Hb, RBC and Pl counts, and ESR, as observed in the female Wistar rats studied. PMID- 27263603 TI - Role of flow cytometry in multiple myeloma and the prognostic significance of CD87 (uPAR) expression. AB - OBJECTIVE: The plasminogen activator system consists of the serine protease urokinase plasminogen activator (uPA), two endogenous inhibitors of PAI-1 (plasminogen activator inhibitor-1) as well as the PAI-2 and uPA receptor (uPAR or CD87). The aim of this study was to determine the significance of flow cytometry and CD87, CD45 and CD56 expressions in the diagnosis, follow-up and prognosis of multiple myeloma (MM). METHODS: Twenty-nine MM patients were included in the study. Bone marrow samples were used for flow cytometry. A panel of CD87, CD45, CD56, CD10, CD19, CD20, CD38, and CD138 was tested by flow cytometry. RESULTS: CD87 was negative in 8 (27.5%) cases, dim positive in 9 (31.1%) and bright positive in 12 (41.4%). CD87 expression was significantly higher in CD45 (-) cases. CONCLUSION: Flow cytometry has a significant role in the diagnosis and prognosis of MM. Further clinical studies including large numbers of patients are needed to determine the prognostic role of CD87 in MM. PMID- 27263604 TI - Enzyme replacement therapy in type 1 Gaucher disease and a review of the literature. AB - Gaucher disease (GD) is the most common lysosomal storage disorder. Deficiency of the lysosomal enzyme glucocerebrosidase results in the intracellular accumulation of undegraded substrates in the spleen, liver and bone marrow. Enzyme replacement therapy (ERT) is a standard approach for type 1 GD. Here, we present an adult patient with hematological disorders due to type 1 GD, who markedly improved with ERT. PMID- 27263605 TI - Cyclic thrombocytopenia: A case report. AB - Cyclic thrombocytopenia (CTP) is a rare disorder characterized by periodic decreases and increases in platelet levels. Each cycle usually spans a period of 3-5 weeks. Clinical features are similar to those of idiopathic thrombocytopenic purpura (ITP), so patients are frequently misdiagnosed as having ITP. However, CTP usually does not respond to most treatments used in ITP such as corticosteroids, splenectomy and intravenous immunoglobulin. In this case report, we present a 33-year-old woman with CTP misdiagnosed as ITP. PMID- 27263606 TI - HbQ-India associated with microcytosis: An uncommon hemoglobin variant associated with a common hematologic condition. AB - HbQ-India is a rare alpha chain variant that usually presents in the heterozygous state. Normally, HbQ-India is clinically silent. It becomes symptomatic when present in association with other conditions. We report a case of HbQ-India with concomitant presence of iron deficiency anemia. A 16-year-old female presented with weakness and pallor intermittently for six years. Complete blood count showed severe microcytic hypochromic anemia. Hemoglobin electrophoresis showed a prominent band in the S,D,G region. Tests for sickling were negative. High performance liquid chromatography (HPLC) showed a peak in the unknown window (4.70-4.90 min) suggestive of HbQ-India. Serum iron profile was suggestive of iron deficiency anemia. Based on the above findings, a diagnosis of coexistent HbQ-India-iron deficiency anemia was made. A family study revealed the father as having moderate anemia with similar findings while the mother was normal. Abnormal hemoglobin in the patient was confirmed by molecular diagnosis. HbQ variants are the alpha globin chain variants due to structural mutations (alpha64 Asp->His) inherited in autosomal dominant fashion. Three molecular variant types have been documented, namely HbQ-India, HbQ-Thailand and HbQ-Iran. Normally, HbQ is clinically silent. Therefore, careful screening of the samples using routine techniques like Hb electrophoresis and HPLC are needed for identification of such abnormal hemoglobin variants like HbQ-India. PMID- 27263607 TI - Severe iron overload and hyporegenerative anemia in a case with rhesus hemolytic disease: therapeutic approach to rare complications. AB - A 33 weeks' gestation, a baby with rhesus hemolytic disease (RHD), who had received intrauterine transfusions twice, developed cholestatic hepatic disease and late hyporegenerative anemia. Her serum ferritin and bilirubin levels increased to 8842 ng/ml and 17.9 mg/dl, respectively. Liver biopsy showed cholestasis and severe iron overload. Treatment with recombinant erythropoietin (rHuEPO) decreased the transfusion need, and intravenous deferoxamine resulted in a marked decreased in serum ferritin levels and normalization of liver function. In patients who have undergone intrauterine transfusions due to RHD, hyperferritinemia and late hyporegenerative anemia should be kept in mind. Chelation therapy in cases with symptomatic hyperferritinemia and rHuEPO treatment in cases with severe hyporegenerative anemia should be considered. PMID- 27263608 TI - Idiopathic thrombocytopenic purpura with venous thrombosis: A case report. PMID- 27263609 TI - The prevalence of factor V 1691G-A mutation in Van region of Turkey. PMID- 27263610 TI - Portal vein thrombosis secondary to Klebsiella oxytoca bacteriemia. PMID- 27263611 TI - Late onset of isovaleric acidemia presenting with bicytopenia. PMID- 27263612 TI - Primary uterine lymphoma of the uterine cervix in advanced age. PMID- 27263613 TI - Leishman-Donovan (LD) bodies in bone marrow biopsy of an adult male with AIDS. PMID- 27263614 TI - Lipoma-Like Bronchogenic Cyst in the Right Chest Sidewall: A Case Report and Literature Review. AB - Bronchogenic cyst most commonly occurs in the mediastinum, followed by the lung. We admitted a 59-year female patient with bronchogenic cyst being uniquely located on the right chest wall of the parietal pleura. Preoperative CT scan showed a local low-density lesion on the right chest wall. The lesion was removed by the thoracoscopic surgery. During the surgical resection, the lesion was observed to be located on the right chest wall. The lesion was surrounded by adipose tissue and covered with entire parietal pleura, which looks like lipoma. Pathological examination demonstrated that the lesion was bronchogenic cyst. In addition, previously reported cases of bronchogenic cyst were reviewed, and the relevant clinical knowledge was discussed. PMID- 27263616 TI - Acute immune thrombocytopenic purpura in children. AB - Immune thrombocytopenic purpura (ITP) in children is usually a benign and self limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. The diagnosis relies on the exclusion of other causes of thrombocytopenia. This paper discusses the differential diagnoses and investigations, especially the importance of bone marrow aspiration. The course of the disease and incidence of intracranial hemorrhage are also discussed. There is substantial discrepancy between published guidelines and between clinicians who like to over-treat. The treatment of the disease ranges from observation to drugs like intravenous immunoglobulin, steroids and anti-D to splenectomy. The different modes of treatment are evaluated. The best treatment seems to be observation except in severe cases. PMID- 27263617 TI - Hematological and biochemical changes in volatile substance abusing street children in Istanbul. AB - The aim of the study is to assess the hematological and biochemical changes of inhalant abusing adolescences in Istanbul, Turkey. The study subjects comprised 24 street children. Demographic characteristics, hematological markers, complete blood count tests and white blood cell differential and liver function tests (alanine transaminase, aspartate transaminase, alkaline phosphatase) were evaluated. The blood cell counts and studied biochemical parameters were within normal range for age and sex matched adolescences. Anemia was observed in only one girl who had hypermenorea. The duration and the amount of substance abuse were investigated for a correlation with the blood parameters, only the amount showed the possibility of a trend associated with Hb and Hct (p<0.05). There was no significant relationship between the parameters except for the age. Although volatile abuse has been supposed to be related with anemia or other hematological abnormalities, we found no significant relation between volatile abuse and hematological or studied biochemical parameters. Alkaline phosphatase was the parameter found to be most affected, though being in normal range. PMID- 27263615 TI - Familial Aggregation of Migraine and Depression: Insights From a Large Australian Twin Sample. AB - OBJECTIVES: This research examined the familial aggregation of migraine, depression, and their co-occurrence. METHODS: Diagnoses of migraine and depression were determined in a sample of 5,319 Australian twins. Migraine was diagnosed by either self-report, the ID migraineTM Screener, or International Headache Society (IHS) criteria. Depression was defined by fulfilling either major depressive disorder (MDD) or minor depressive disorder (MiDD) based on the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. The relative risks (RR) for migraine and depression were estimated in co-twins of twin probands reporting migraine or depression to evaluate their familial aggregation and co-occurrence. RESULTS: An increased RR of both migraine and depression in co-twins of probands with the same trait was observed, with significantly higher estimates within monozygotic (MZ) twin pairs compared to dizygotic (DZ) twin pairs. For cross-trait analysis, the RR for migraine in co twins of probands reporting depression was 1.36 (95% CI: 1.24-1.48) in MZ pairs and 1.04 (95% CI: 0.95-1.14) in DZ pairs; and the RR for depression in co-twins of probands reporting migraine was 1.26 (95% CI: 1.14-1.38) in MZ pairs and 1.02 (95% CI: 0.94-1.11) in DZ pairs. The RR for strict IHS migraine in co-twins of probands reporting MDD was 2.23 (95% CI: 1.81-2.75) in MZ pairs and 1.55 (95% CI: 1.34-1.79) in DZ pairs; and the RR for MDD in co-twins of probands reporting IHS migraine was 1.35 (95% CI: 1.13-1.62) in MZ pairs and 1.06 (95% CI: 0.93-1.22) in DZ pairs. CONCLUSIONS: We observed significant evidence for a genetic contribution to familial aggregation of migraine and depression. Our findings suggest a bi-directional association between migraine and depression, with an increased risk for depression in relatives of probands reporting migraine, and vice versa. However, the observed risk for migraine in relatives of probands reporting depression was considerably higher than the reverse. These results add further support to previous studies suggesting that patients with comorbid migraine and depression are genetically more similar to patients with only depression than patients with only migraine. PMID- 27263618 TI - Effects of sub-acute exposure to static magnetic field on iron status and hematopoiesis in rats. AB - The present work was undertaken in order to investigate the effects of static magnetic field (SMF) on hematopoiesis and iron metabolism in male rats. At thermoneutrality (25 degrees C), the exposition of rats to SMF (128 mT, 1h/day for 5 consecutive days) induced an increase of hematocrit (+12%, p<0.05), hemoglobin (+6%, p<0.05) and mean corpuscular hemoglobin concentration (+9%, p<0.05). SMF exposure increased the plasma transferrin concentration (+25%, p<0.05) and the capacity of iron saturation in transferrin (+24%, p<0.05). However, the plasma iron level and the coefficient of transferrin saturation decreased (respectively 17% and 33%; p<0.05) in exposed rats. Our investigations suggested that SMF induced modifications in hematological and mineral parameters, indicating the development of hypoxia-like status associated with iron deficit in rats. PMID- 27263619 TI - Gastric and non-gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: A single-center experience. AB - Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is a distinct lymphoma with specific clinical and pathological features that occurs in diverse anatomic locations. We conducted this retrospective study to demonstrate our experience in patients with MALT lymphomas and compare our results with the literature. We studied 23 patients with histologically confirmed diagnosis of MALT lymphomas (12 with gastric, 11 with non-gastric localization) treated during the past 13 years. The female/male ratio of patients was 15/8 with a median age at presentation of 56 years (range 27-88 years). 16 patients (70%) with stage I and II, 7 patients (30%) with stage III and IV were admitted. At presentation 93% of patients had good performance status (ECOG<2) and 5 (22%) had B-symptoms. There was no difference between gastric and non-gastric MALT lymphomas when compared with sex, age, ECOG performance status, stage of the disease. Patients were treated with different treatment modality; H. Pylori eradication only (8.6%), radiotherapy only (21.7%), surgery alone (4.%) or followed by radiotherapy (26%) or chemotherapy (21.7%). All the patients are alive with a median 33 months (range 8-153 months) of follow-up and the 5- year PFS in gastric lymphoma and non-gastric lymphoma were 86% and 84% respectively with no statistical difference (p=0.5). Because of the indolent course the prognosis of MALT lymphoma was good regardless of the treatment modalities. The treatment choice should be patient-tailored, taking into account the site, stage, age and other clinical characteristic of patient. PMID- 27263620 TI - Lupus anticoagulant and anticardiolipin antibodies in SLE with secondary Antiphospholipid Antibody Syndrome. AB - Thirty patients with systemic lupus erythematosus (SLE) and suspected secondary antiphospholipid antibody syndrome (APLAS) were evaluated in the study based on their clinical manifestations. The aim was to study the prevalence of various antiphospholipid antibodies, compare the tests used for their detection and to find a correlation between clinical and laboratory parameters. Coagulation tests used were activated partial thromboplastin time, dilute Russell viper venom time and kaolin clotting time and the results were analyzed statistically. In our study, arteriovenous thrombosis was more common than recurrent abortions and other clinical manifestations. Twelve percent of patients had positive lupus anticoagulant and 78% had elevated anticardiolipin antibody titers. We concluded that the prevalence of lupus anticoagulant and anticardiolipin antibodies in SLE patients with secondary APLAS was 12% and 17%, respectively. We also proved that dilute Russell viper venom time and kaolin clotting time proved to be much more specific tests and the anticardiolipin antibody a much more sensitive test. PMID- 27263621 TI - Retrospective analysis of seven patients with adult-onset langerhans cell histiocytosis syndromes: A single center experience. AB - Langerhans cell histiocytosis syndromes have been described as encompassing a range of disorders, such as eosinophilic granuloma, Letterer-Siwe syndrome and Hand-Schuller-Christian disease. These disorders have been mainly diagnosed at early ages of life and are relatively rare entities in adult age groups. In this study, we aimed to retrospectively evaluate the patients with Langerhans cell histiocytosis followed-up in our hospital. Seven patients were treated between 1995 and 2005. Median age of patients was 27.5 (18-40) years. Main complaints were classified as bone pain in multiple sites (100%), polydipsia (28%), lung infiltration (14%), oral mucosal infiltration (14%), and cranial nerve infiltration (14%). Two patients were diagnosed as Hand-Schuller-Christian disease, and the others were accepted as eosinophilic granuloma. There was no bone marrow or any other organ infiltration except lung infiltration in one patient. Bone infiltration was the prominent sign in all patients with a minimum of one to maximum of seven different sites. All patients were alive during the follow-up period. All patients were treated with radiotherapy except one patient treated with chemotherapy regimen started with vincristine plus dexamethasone and continued with cladribine. Three of seven patients were treated with combined modality, one patient with only chemotherapy and the others with only radiotherapy. There was no grade 3-4 hematological or systemic side effects of treatment. Relapses were detected in only two patients as new bone infiltrations which responded completely to radiotherapy. Langerhans cell histiocytosis syndromes have a relatively benign course in adult patients and can be treated with either radiotherapy or chemo-radiotherapy successfully. PMID- 27263622 TI - An autoimmune lymphoproliferative syndrome initially diagnosed as Evans syndrome. AB - Autoimmune lymphoproliferative syndrome (ALPS) is a rare childhood disorder characterized by chronic non-malignant lymphoproliferation and autoimmunity. Patients with ALPS frequently exhibit episodic and intermittent, severe autoimmune- induced hemolytic anemia, thrombocytopenia or combined cytopenias. The co-occurrence of immune-mediated cytopenias, autoimmune thrombocytopenia and autoimmune hemolytic anemia is also known as Evans syndrome. This report describes a child who presented with Evans syndrome symptoms and who, after the detection of increased percentage of double negative T cell population in the peripheral blood, was diagnosed as ALPS. He received several courses of treatment including glucocorticoids, cyclosporine A (Cs A), and intravenous immunoglobulin (IVIG) without any clinical benefit and was treated with the antimalarial drug Fansidar(r). With administration of Fansidar(r) (half tablet per week; containing 250 mg of pyrimethamine and 12.5 mg of sulfadoxine) combined with immunosuppressive drugs, clinical status and laboratory findings temporarily improved. After two months, the patient underwent laparoscopic splenectomy because of worsening of thrombocytopenia refractory to the treatment. There was a transient beneficial effect from splenectomy. We were unable to stop immunosuppressive therapy and Fansidar(r); however, this combined therapy was successful in decreasing the number of hospitalizations and controlled his clinical symptoms more effectively for six months. Unfortunately, he was admitted to a regional hospital with high fever and died at the age of three. PMID- 27263624 TI - Sea-blue histiocytes in bone marrow aspiration sample: what is the importance? PMID- 27263623 TI - Therapy-related myelodysplastic syndrome following acute promyelocytic leukemia and biphenotypic acute leukemia following stem cell transplantation in the same patient. AB - Therapy-related myelodysplastic syndrome in patients with acute promyelocytic leukemia is a rare event and the prognosis is poor. Allogeneic bone marrow transplantation is recently being reported as an effective treatment. We present a young patient with acute promyelocytic leukemia who developed myelodysplastic syndrome 52 months after complete remission. She underwent allogeneic peripheral blood stem cell transplantation but relapsed with biphenotypic leukemia after five months. To our knowledge, this is the first case to relapse with acute biphenotypic leukemia after allogeneic peripheral stem cell transplantation for therapy-related myelodysplastic syndrome following acute promyelocytic leukemia. PMID- 27263625 TI - The prevalence of factor V Leiden (1691G-A) and methylenetetrahydrofolate reductase C677T mutations in healthy newborns in Bursa, Turkey. PMID- 27263626 TI - Richness and distribution of tropical oyster parasites in two oceans. AB - Parasites can exert strong effects on population to ecosystem level processes, but data on parasites are limited for many global regions, especially tropical marine systems. Characterizing parasite diversity and distributions are the first steps towards understanding the potential impacts of parasites. The Panama Canal serves as an interesting location to examine tropical parasite diversity and distribution, as it is a conduit between two oceans and a hub for international trade. We examined metazoan and protistan parasites associated with ten oyster species collected from both Panamanian coasts, including the Panama Canal and Bocas del Toro. We found multiple metazoan taxa (pea crabs, Stylochus spp., Urastoma cyrinae). Our molecular screening for protistan parasites detected four species of Perkinsus (Perkinsus marinus, Perkinsus chesapeaki, Perkinsus olseni, Perkinsus beihaiensis) and several haplosporidians, including two genera (Minchinia, Haplosporidium). Species richness was higher for the protistan parasites than for the metazoans, with haplosporidian richness being higher than Perkinsus richness. Perkinsus species were the most frequently detected and most geographically widespread among parasite groups. Parasite richness and overlap differed between regions, locations and oyster hosts. These results have important implications for tropical parasite richness and the dispersal of parasites due to shipping associated with the Panama Canal. PMID- 27263627 TI - Spotlight on the ligand: luminescent cyclometalated Pt(iv) complexes containing a fluorenyl moiety. AB - The synthesis, electrochemistry and photophysical properties of a family of Pt(iv) complexes with cyclometalated 2-(9,9-dimethylfluoren-2-yl)pyridine (flpy) are reported. Homoleptic and heteroleptic tris-cyclometalated complexes with a meridional configuration, mer-[Pt(C^N)2(flpy)]OTf, with C^N = flpy or cyclometalated 2-phenylpyridine (ppy), were prepared by reacting the bis cyclometalated precursors [Pt(C^N)2Cl2] with flpyH in the presence of two equivalents of AgOTf. The corresponding facial isomers were obtained by photoisomerization. The Pt(iv) complexes with flpy display intense absorptions in the near-visible region and yellow phosphorescence in fluid solutions at 298 K, with quantum yields in the range 0.06-0.28 and lifetimes of hundreds of microseconds. The emissions arise from essentially (3)LC(flpy) states in all cases, with little metal-orbital contribution. However, computational calculations and experimental data demonstrate that subtle variations in the contribution of metal orbitals to the emitting state have a profound impact on quantum yields, while nonradiative deactivation through the thermal population of deactivating LMCT states does not have a significant influence. PMID- 27263628 TI - Dynamic mechanoelectrochemistry of polypyrrole membranes via shear-force tracking. AB - Mechanoelectrochemistry is the study of elastic and plastic deformation of materials during reversible reduction and oxidation processes. In this article, we introduce shear-force tracking as a method to dynamically measure mechanical (strain), chemical (ion transport), and electrical (applied redox potentials) responses of the conducting polymer polypyrrole (PPy) during redox reactions. This tracking technique uses a control algorithm to maintain a set distance between a ultramicroelectrode (UME) tip and a surface via shear-force regulation. Due to the sensitivity of shear-force signals in the near field of substrate surfaces, a significantly improved signal to noise ratio (20 : 1) is possible and allows for nanoscale measurement of redox events. Chemomechanical coupling (the ratio of ion transport to resultant extensional actuation) is calculated for PPy based membranes of various thicknesses based on a mechanistic interpretation of charge storage in redox active conducting polymers. The measured dynamic response demonstrates that chemomechanical coupling is not a constant, as assumed in literature, but is dependent on the polymers state of charge and the direction (ingress/egress) of ion transport. PMID- 27263629 TI - Are fragment-based quantum chemistry methods applicable to medium-sized water clusters? AB - Fragment-based quantum chemistry methods are either based on the many-body expansion or the inclusion-exclusion principle. To compare the applicability of these two categories of methods, we have systematically evaluated the performance of the generalized energy based fragmentation (GEBF) method (J. Phys. Chem. A, 2007, 111, 2193) and the electrostatically embedded many-body (EE-MB) method (J. Chem. Theory Comput., 2007, 3, 46) for medium-sized water clusters (H2O)n (n = 10, 20, 30). Our calculations demonstrate that the GEBF method provides uniformly accurate ground-state energies for 10 low-energy isomers of three water clusters under study at a series of theory levels, while the EE-MB method (with one water molecule as a fragment and without using the cutoff distance) shows a poor convergence for (H2O)20 and (H2O)30 when the basis set contains diffuse functions. Our analysis shows that the neglect of the basis set superposition error for each subsystem has little effect on the accuracy of the GEBF method, but leads to much less accurate results for the EE-MB method. The accuracy of the EE-MB method can be dramatically improved by using an appropriate cutoff distance and using two water molecules as a fragment. For (H2O)30, the average deviation of the EE-MB method truncated up to the three-body level calculated using this strategy (relative to the conventional energies) is about 0.003 hartree at the M06-2X/6-311++G** level, while the deviation of the GEBF method with a similar computational cost is less than 0.001 hartree. The GEBF method is demonstrated to be applicable for electronic structure calculations of water clusters at any basis set. PMID- 27263631 TI - Low-temperature solution-processed p-type vanadium oxide for perovskite solar cells. AB - A low-temperature solution-processed inorganic p-type contact material of vanadium oxide (VOx) was developed to fabricate planar-heterojunction perovskite solar cells. Using a solvent-assisted process, high-quality uniform and compact perovskite (CH3NH3PbI3) films were deposited on VOx coated substrates. Due to the high transmittance and quenching efficiency of VOx layers, a power conversion efficiency of over 14% was achieved. PMID- 27263630 TI - Attractive interaction between Mn atoms on the GaAs(110) surface observed by scanning tunneling microscopy. AB - Scanning tunneling microscopy/spectroscopy (STM/STS) was carried out to investigate the structures of Mn atoms deposited on a GaAs(110) surface at room temperature to directly observe the characteristics of interactions between Mn atoms in GaAs. Mn atoms were paired with a probability higher than the random distribution, indicating an attractive interaction between them. In fact, re pairing of unpaired Mn atoms was observed during STS measurement. The pair initially had a new structure, which was transformed during STS measurement into one of those formed by atom manipulation at 4 K. Mn atoms in pairs and trimers were aligned in the <110> direction, which is theoretically predicted to produce a high Curie temperature. PMID- 27263632 TI - Chemotherapy resistance in Acute Leukemia. AB - Drug resistance markers are often predictive of treatment response and outcome in patients with acute myeloid leukemia. The immunologic detection of drug efflux pumps such as P-glycoprotein (Pgp) and multidrug resistance associated protein 1 (MRP1) rrelate with functional assays of drug resistance and these drug accumulation defects also appear operable in ALL. Other markers such as LRP, bcl- 2, and BRCP, have been described in patients with AML although their pathophysiology and clinical relevance is less clear and methodology for their quantification not well standardized. Preclinical tudies have shown that small molecules capable of reversing efflux can restore drug sensitivity in resistant tumor models. While initial clinical studies were limited by both potency and specificity of the reverser, later studies with more effective reversers have in many instances been limited by pharmacokinetic interactions exacerbating the clinical toxicities of chemotherapy. Nonetheless, one large randomized study using cyclosporine has demonstrated a proven survival advantage without increased toxicity, although the inconsistent results with other modulators raises doubt as to the utility and overall strategy of using drug efflux blockers in patients with established Pgp overexpression. Most of these patients have additional mechanisms of resistance and achieving meaningful clinical responses will likely require more complex clinical strategies. Preventing or delaying development of drug resistance in chemosensitive patientsrepresents another therapeutic strategy to be tested. PMID- 27263633 TI - The Differential Diagnosis of Lymphocyte-rich Classical Hodgkin's Lymphoma and Lymphocyte Predominant Hodgkin's Lymphoma Using the R.E.A.L. Criteria. An Immunohistochemical Study on 45 Cases. AB - In the present study, the two types, lymphocyte-rich classical HL (LRCHL) and nodular lymphocytepredominant type (NLPHL), which were grouped together before the R.E.A.L. classification, were questioned on the basis of differential criteria and 45 cases were retrieved from last ten years' archival material. On histopathological examination, nodular pattern, the cytological features and intensity of Reed- Sternberg (RS) cells, the pattern and intensity of histiocytes, the presence of germinal centers with progressive transformation were analysed. An immunohistochemical study was performed using antibodies against CD20, CD45RO, CD3, CD30, CD15 antigens and streptavidin-biotin procedure. The cases were classified into three groups according to the histologic pattern and immunophenotypical features ofthe RS cells: I) diffuse, LRCHL (CD20-, CD30+/ , CD15+/-): n= 28; II) NLPHL (CD20+, CD30-, CD15-): n= 11; III) cases which could not be evaluated in former groups: n= 6. Four cases in the latter group showed a nodular pattern with RS cells negative for all markers, except for one case, which expressed both CD20 and CD15. The remaining two cases exhibited a diffuse pattern and the RS cells were CD20+, coexpressing CD30 in one. These findings suggest that, differential diagnosis according to the R.E.A.L. criteria is not distinctive between the two categories of HL in about 13% of cases, and further criteria need to be established to define the grey zone between the two entities which might lead to further therapeutic trials. PMID- 27263634 TI - Donor Leukocyte Infusions for the Treatment of Leukemia Relapse After Allogeneic Hematopoietic Cell Transplantation with Myeloablative Conditioning. AB - Leukemic relapse after allogeneic transplantation is a difficult problem. Conventional treatment modalities or second transplants have not provided the sustained complete remissions on the whole. Reinfusion and activation of cytotoxic T lymphocytes of the donor seem to be effective and it has been understood that the success of the transplantation depends mainly on graft versus leukemia effect. Thirteen patients with leukemia (8 CML, 5 AML) who had relapsed after allogeneic hematopoietic cell transplantation (HCT) with myeloablative conditioning, have received donor leukocyte infusions (DLI). The median time between transplantation and relapse was 18 months (4-57 months). For CML patients who had cytogenetic or hematologic relapse, IFN alpha 2b was started at a dose of 5 million units/m2/d for every consecutive days. Starting from the fifth week of this treatment, unprimed donor peripheral blood mononuclear cells were infused to the patients once a week for four weeks. IFN treatment was not cessated during these infusions, and was given for 12 weeks totally. For relapsed acute leukemia patients, standart chemotherapy regimens as for AML were used. After the treatment, donor lymphocytes which were obtained from the original HCT donor who was primed with G-CSF were given. After recovery, IFN alfa2b was started 5 million U/m2/d each consecutive day until the GVHD findings were observed. GVHD prophylaxis was not made after DLIs. Acute GVHD was seen in 11 of 13 patients. Four patients developed chronicGVHD. Among 13 patients, four patients are alive and they have been in complete remission for 23 to 76 months. The other patients were not alive due to mostly disease progression. Two patients died because of advanced GVHD. In our practice, the patients with progressive disease were not the well responded ones. These observations suggest that there is a limit for the immune effect regarding the number of the tumor cells and their proliferative capacity. Chemotherapy, which does not suppress immunity, may give time and chance to allogeneic lymphocytes to affect. PMID- 27263635 TI - Prognostic significance of wilms tumor 1 gene in childhood acute Lymphoblastic Leukemia. AB - Wilms tumor 1 (WT1) gene is a tumor supressor gene, expressed in malignant and normal hematopoietic progenitor cells. Prognostic significance of this gene in childhood acute lymphoid leukemia (ALL) is not clear. We evaluated the presence of WT1 expression in bone marrow samples of 28 children with de novo ALL at diagnosis by two step RT-PCR. Expression of WT1 gene was detected in 78.5% of patients. There was no correlation between WT1 gene expression and age, sex, FAB type, leukocyte count, and presence of t(4;11) and t(9;22). All patients were treated with modified BFM 86 protocol. There was no difference in the complete remission (CR) rate between WT1 positive and negative patients. Event free survival (EFS) and overall survival (OS) of WT1 positive and negative patients were also not significant. We conclude that expression of WT1 gene is not associated with specific characteristics of ALL blast cells and is not a prognostic factor for CR, remission duration and overall survival. PMID- 27263636 TI - Biological Dosimetry of Co-60 Gamma Irradiation. AB - Development of radiation technology has resulted in increasing numbers of people working with it. Therefore it has increasingly been important to monitor the radiation in order to ensure public safety. Physical dosimetry plays an important role in monitoring. But a need arise for biological dosimetry where physical dosimetry is absent or its presence is insufficient. In this study Co-60 gamma radiation dose-response curves for chromosome aberrations were determined for use as controls in biological dosimetry. Peripheral blood that were taken from healthy individuals not working with radiation were irradiated at different radiation doses. The relationship between unstable chromosome aberrations in metaphaseblocked cells and radiation dose were drawn by using the linear quadratic (LQ) formula. The absorbed radiation doses of the test group consisting of five people that had been working with Co-60 teletherapy machines were estimated using the LQ parameters of control dose-response curves in the Qdr method. Estimated radiation doses were below the permissible radiation dose limits for four workers, but one worker's estimated dose was higher than these limits. PMID- 27263637 TI - Detection of BCR/ABL transcripts by reverse transcriptase polimerase chain reaction in pediatric acute Lymphoblastic Leukemia: incidence and clinical eatures. AB - BCR/ABL expression, which is the molecular equivalent of the Philadelphia chromosome, is an independent poor risk factor in acute lymphoblastic leukemia (ALL). We used a two-step (nested) reverse transcriptase polimerase chain reaction (RT-PCR) assay to examine BCR/ABL expression in the diagnostic bone marrow specimen of children with ALL, prospectively. Among 75 de novo ALL patients, 4 (%5.3) were found to be BCR/ABL- ositive, whereas 4 of 17 relapsed patients (23.5%) were positive. This preliminary study in Turkish children showed an incidence similar to reports from Europe and the U.S.A. More intensive chemotherapies and allogeneic bone marrow transplantations (BMT) uring the first remission were planned if a donor was available. Out of 8 BCR/ABL-positive patients, complete remission (CR) was achieved in 7 patients and partial remission (PR) was achieved in 1 patient. Three patients underwent allogeneic BMT during the first CR and 1 under went autologous BMT during the first PR. The Kaplan-Meier estimate of vent-free survival (EFS) of BCR/ABL negative de novo ALL patients was 78.36% at 3 years, whereas the EFS of positive patients was 31.25% at 26 +/- 6.4 months. Molecular screening for the Philadelphia chromosome should become a part of the routine diagnostic panel in ALL patients in order to predict which patients have a poor prognosis and need tailored therapy. PMID- 27263638 TI - Impact of Fluorescence in Situ Hybridization in the Detection of Cryptic Fusion Transcript PML/RARA and A Complex t(5;15;17) in a Case of Acute Promyelocytic Leukemia. AB - Genetic aspects of a 28 year-old female patient with typical morphological and clinical features of acute promyelocytic leukemia is presented. Pml/rara fusion transcript and a complex translocation involving chromosomes 5, 15 and 17 were detected by fluorescence in situ hybridization (FISH) technique which was applied as in adjunct to conventional cytogenetics. The patient deceased soon in spite of the immediate ATRA and cytostatic therapy. PMID- 27263639 TI - Paroxysmal Nocturnal Haemoglobinuria in the Differential Diagnosis of Unresponsive Iron Deficiency Anemia: A Case Report. AB - A 16-year-old male patient who was on oral iron treatment for iron deficiency anemia for the last one year was seen at the Haematology clinic with complaints of weakness, pallor, and jaundice. A complete blood count revealed Hb of 4.2 mmol/L, Hct of 0.14, and MCV of 76 fl. A blood smear showed 50% neutrophils, 40% lymphocytes, and 10% monocytes with anisocytosis, poikilocytosis, polichromasia in erythrocytes and normoblasts. Reticulocyte count was under 1%. There was a slight erythroid hyperplasia in the bone marrow aspiration. Biochemical examinations showed total bilirubin of 3.9 mg/dL, indirect bilirubin of 3.4 mg/dL, and lactate dehydrogenase (LDH) of 6085 U/L (220-450). In re-evaluating the history of the patient, he was seen to be complaining of dark discoloration of morning urine. Perl's reaction was found to be positive for hemosiderin in the urine sediment. Because Ham's test was positive, the levels of CD55, 58, and 59 proteins on erythrocyte membranes were found to be lower. The patient was started 32 mg of methylprednisolone and his anaemia was improved by the 14th day of treatment. When evaluating iron deficiency anemia resistant to iron supplementation, PNH should be kept in mind. PMID- 27263640 TI - Congenital Hypofibrinogenemia: A Newborn Infant with Cord Bleeding. AB - The genetic disorders causing decreased fibrinogen synthesis may be caused by heterozygous (hypofibrinogenemia) or homozygous (afibrinogenemia) deficiency. The consequences of the disorders are gastrointestinal bleeding, cord bleeding, eccymoses, subcutaneous hematomas and hemarthroses especially due to traumatic delivery in the neonatal period. Laboratory evaluation of the patient with hypofibrinogenemia reveals prolongation of thrombin time, partial thromboplastin time, prothrombin time and decreased fibrinogen level. We report a 21 days old, congenital hypofibrinogenemia case with cord bleeding. PMID- 27263641 TI - On the origin of vorticity in magnetic particle suspensions subjected to triaxial fields. AB - We have recently reported that two classes of time-dependent triaxial magnetic fields can induce vorticity in magnetic particle suspensions. The first class - symmetry-breaking fields - is comprised of two ac components and one dc component. The second class - rational triad fields - is comprised of three ac components. In both cases deterministic vorticity occurs when the ratios of the field frequencies form rational numbers. A strange aspect of these fields is that they produce fluid vorticity without generally having a circulating field vector, such as would occur in a rotating field. It has been shown, however, that the symmetry of the field trajectory, considered jointly with that of the converse field, allows vorticity to occur around one particular field axis. This axis might be any of the field components, and is determined by the relative frequencies of the field components. However, the symmetry theories give absolutely no insight into why vorticity should occur. In this paper we propose a particle-based model of vorticity in these driven fluids. This model proposes that particles form volatile chains that follow, but lag behind, the dynamic field vector. This model is consistent with the predictions of symmetry theory and gives reasonable agreement with previously reported torque density measurements for a variety of triaxial fields. PMID- 27263642 TI - Therapeutic Angiogenesis by Autologous Transplantation of Bone Marrow Mononuclear Cells for Buerger's Patients with Retractable Limb Ischaemia: A Preliminary Report. AB - Bone marrow implantation into ischaemic limbs could enhance angiogenesis by supplying endothelialprogeniter cells and angiogenic cytokinesot factors. We investigated efficacy and safety of autologousimplantation of bonemarrow mononuclearcells (BMMC)in patients with ischaemic limbs due to Buerger's disease. We commence daciinical study to test cell therapy with autologous BMMC in patients with ischaemic limbs at the University of Ankara School of Medicine. In order for the patients to qualify for BMMC implantation, they should have critical limb ischaemia define das ischaemic rest painin a limb with or without non healing ulcers, should not respond to previous iloprost infusions and smoking cessation six months prior to evaluation and should not be candidates for nonsurgicalor surgical revascularisation. Primaryend points were safety andfeasibility of the treatmentand total healing of the most importantlesion. Secondary endpoints were total relief of rest pain without the need for analgesies,change in peak walkingtime (PWT)at 12 weeks, improvements in ankle brachial pressure index(ABI), transcutaneous oxygen saturation using pulse oximetry(SaO2),angiographic evidence of newcollatera lvesselformation, tissue perfusion in the affected extremity using Thallium perfusions cintigraphyW. hilepatients(meanage46.7: !: 10.3years)were undergeneraal naesthesiaw, eharvested bonemarrow(519: t 45.5mUfromtheposteridilriacspineA. fterredbloodcell(RBCd) epletiaannd volumereduction using a continuous flow cell separator,we achieved 91% RBC depletian and concentrated /~MMC to a final volume and concentration of 51.5: t io.1 mLand7.04: t 1.9 x ioe7/mL total nucleated cells, respectively W.eimplantedBMMC (mean12.16: t 4.3 x ioe8) within three hours after marrow aspiration by intramuscular injection into the gastrocnemiusmuscle of ischaemic legs. Isotonic saline were injected into the other extremityin as similar fashion as control. 13 Unilateral intramuscular administration of BMMC was not associated with any complications. The primary efficacy end point, total healing of the most importantlesion, was achieved in three patients. All patients were followed up for at least four weeks. The secondary measures; change in PWT(LlPWT)at 12 weeks, total relief of rest pain without the need of analgesics improved in three patjents. These improvements were sustained for 24 weeks in the first two patients. Digital subtraction angiographic studies before and 3 months after the BMMC implantation showed the presence of a new vascular collateral network across the affected arteries in three patients. Preliminary results of the presentedstudy are promising. Thus, bone marrow maybe a potential source of cells for Buerger'spatients with end-stage Iimbischaemia refractory to other medical treatment modalities. PMID- 27263643 TI - Rapid Detection of the Apoptosis Related Genes (BCL-2, BAD, BAX) in 12 Hours 1,25 (OH)2D3 Treated HL-60 Cells Using Real-Time Quantitative RT-PCR. AB - HL-60 cell line offers an interesting model to study apoptosis. Our aim was to detect the expressions of three apoptotic genes (BCL-2, BAD and BAX) using Real Time quantitative polymerase chain reaction (PCR). HL-60 cells were incubated with 1,25 (OH)2D3 (5 x 10-8 M). RNA portions were isolated and LightCycler analysis were performed on cDNA samples. 1,25 (OH)2D3 incubated cell portions were compared to nontreated portions. We observed down-regulated levels of three genes at the end of the 12 hours. Gene expression ratios were 0.98 for BAX, 0.41 for BAD, 0.81 for BCL-2. For the first time, this study represents the expression levels of these three apoptosis related genes together during early phase (12 hours) of 1,25 (OH)2D3 treatment of HL-60 cells. Data indicate that expression differences of these apoptosis genes take place so early in exposure to 1,25 (OH)2D3. This optimised strategy would be used in rapid understanding of similar apoptotic deregulations. PMID- 27263644 TI - Anti-D and Intravenous Immunoglobulin Treatments in Chronic Idiopathic Thrombocytopenic Purpura. AB - The aim of this prospective study was to evaluate the data from 29 patients diagnosed as chronic refractory idiopathic thrombocytopenic purpura (ITP) treated with anti-D immunoglobulin and intravenous immunoglobulin G (IVIG). We used anti D and IVIG in 11 and 18 patients respectively in whom the previous treatments including corticosteroids and splenectomy had been unsuccessful. The complete response rates were significantly higher in IVIG arm (55.5% to 18.1%) with a duration of 8 weeks. The overall efficacy of IVIG in the chronic ITP is similar to previous data, however we found lower platelet responses in patients treated with anti-D that can be attributed to the lower sucess in the splenectomized patients. PMID- 27263645 TI - Report of a Family with Fanconi Anemia and Ataxia-Telangiectasia. AB - We diagnosed two boys with two different chromosomal instability disorders such as Fanconi anemia (FA) and ataxia-telangiectasia (AT) in the same family. The phenotype of the first sibling supports the diagnosis of ataxia-telangiectasia. He had ataxia, telangiectasias on bulbar conjunctivas, a high level of alpha fetoprotein, low levels of IgA and IgE, and a defective cell-mediated immunity. Cytogenetic studies of the peripheral lymphocytes revealed a chromosomal sensitivity to ionizing radiation. His 8-years-old brother had pancytopenia but had no ataxia and telangiectasia. He had a normal level of immunoglobulins and alpha-fetoprotein. His cell-mediated immunity was also normal. Cytogenetic studies showed no evidence spontaneus chromosome aberrations; however, there was a mild increase in the rate of diepoxybutane (DEB) and also an increased chromosome aberrations in the mitomycin C (MMC) treated samples than the control. The parent of the boys and 5th child were healty. The first child had normal hematological and immunological features, but he had a mild increase in the rate of DEB. The 4th child had an increased rate of DEB-induced chromosome aberrations. To our knowledge, this is the first family with FA and AT in Turkey and it is reported because of its rarity. PMID- 27263646 TI - Primary Uterine Lymphoma: A Rare Cause of Postmenopausal Bleeding. AB - Although uterus and cervix infiltration is a frequent finding in the later stages of lymphomatous disease, non-Hodgkin's lymphoma (NHL) of the female genital tract is extremely rare. We present the case of a 63-years- old woman diagnosed with postmenopausal bleeding, Ann Arbor stage IE, primary, diffuse, large B-cell NHL of the uterus. Disease status was monitored with physical examination and imaging studies. We administered chemotherapy according to CHOP protocol (cyclophosphamide, adriamycin, vincristine, and prednisone). Primary pelvic NHL may present symptoms like other more common gynecologic cancers. It should be considered in the differential diagnosis of gynecologic malignancy. Our case emphasizes the importance of chemotherapy that can provide a control of the distant microscopic metastases. PMID- 27263647 TI - A Case with Chronic Eosinophilic Leukaemia Resulting in Blastic Transformation. AB - Chronic eosinophilic leukaemia is a rare myeloproliferative disease different from the chronic myeloid leukaemia. It is a haematologic malignancy that must be considered separately from other causes of eosinophilia due to its remarkable clonal eosinophilia. Here, we describe a case with chronic eosinophilic leukaemia which was initially hypereosinophilic (eosinophil count: 85.4 x 109/L) and displayed blastic transformation after a 9 months follow up. We suggest the invasion of spleen, probable invasion of the liver and the blastic transformation of this case must be discerned as a different entity rather than the other causes of eosinophilia. PMID- 27263649 TI - Microorganisms Isolated from Blood Cultures of Febrile Neutropenic Patients in Ibn-i Sina Hospital. PMID- 27263648 TI - Images in Hematology. PMID- 27263650 TI - Horizontal Pigmented Nail Bands During Daunorubicin Treatment. PMID- 27263651 TI - Thromboembolism in Patients with Cancer. AB - One hundred and forty years ago, Armand Trousseau described phlegmasia alba dolens as a sign of internal malignancy. Nowadays, it is commonly believed that the presence malignant tumaor increases the risk of venous thromboembolism (i.e deep vein thrombosis and pulmonary embolism) However, cancer is usually associated with other factors such as old age, extensive surgery,immobility, etc., which may predispose to thromboembolism. The majority of thrombotic events occur in the venous system; the incidence of arterial thrombosis is much lower.Recurrent thromboembolism in cancer patients frequently and diminishes the quality of life of the patients.Furthermore, if the thromboembolism is massive, destipte of early and aggressive treatment, it may result in death. In this article, we review thromboembolic complications in cancer patients. PMID- 27263652 TI - Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death. AB - Curcumin (CUR) and berberine (BBR) are renowned natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. However, the anticancer capacity of either CUR or BBR is limited. This prompted us to investigate the chemopreventive potential of co-treatment of CUR and BBR against breast cancers. The results showed that CUR and BBR in combination synergistically inhibited the growth of both MCF-7 and MDA-MB-231 breast cancer cells than the compounds used alone. Further study confirmed that synergistic anti-breast cancer activities of co-treatment of these two compounds was through inducing more apoptosis and autophagic cell death (ACD). The co-treatment-induced apoptosis was caspase-dependent and through activating ERK pathways. Our data also demonstrated that co-treatment of CUR and BBR strongly up-regulated phosphorylation of JNK and Beclin1, and decreased phosphorylated Bcl-2. Inhibition of JNK by SP600125 markedly decreased LC3-II and Beclin1, restored phosphorylated Bcl-2, and reduced the cytotoxicity induced by the two compounds in combination. These results strongly suggested that JNK/Bcl-2/Beclin1 pathway played a key role in the induction of ACD in breast cancer cells by co-treatment of CUR and BBR. This study provides an insight into the potential application of curcumin and berberine in combination for the chemoprevention and treatment of breast cancers. PMID- 27263653 TI - Controlling thermal emission with refractory epsilon-near-zero metamaterials via topological transitions. AB - Control of thermal radiation at high temperatures is vital for waste heat recovery and for high-efficiency thermophotovoltaic (TPV) conversion. Previously, structural resonances utilizing gratings, thin film resonances, metasurfaces and photonic crystals were used to spectrally control thermal emission, often requiring lithographic structuring of the surface and causing significant angle dependence. In contrast, here, we demonstrate a refractory W-HfO2 metamaterial, which controls thermal emission through an engineered dielectric response function. The epsilon-near-zero frequency of a metamaterial and the connected optical topological transition (OTT) are adjusted to selectively enhance and suppress the thermal emission in the near-infrared spectrum, crucial for improved TPV efficiency. The near-omnidirectional and spectrally selective emitter is obtained as the emission changes due to material properties and not due to resonances or interference effects, marking a paradigm shift in thermal engineering approaches. We experimentally demonstrate the OTT in a thermally stable metamaterial at high temperatures of 1,000 degrees C. PMID- 27263654 TI - Impermeable flexible liquid barrier film for encapsulation of DSSC metal electrodes. AB - Encapsulation of electronic devices such as dye-sensitized solar cells (DSSCs) is prone to degradation under normal atmospheric conditions, even with hermetic barriers on the metal electrodes. Overcoming this problem is crucial to increasing DSSC lifetimes and making them commercially viable. Herein, we report a new impermeable flexible liquid barrier film using polyvinyl alcohol (PVA) and partially reduced graphene oxide (PrGO), which dramatically enhances the lifetime of Ag metal electrodes (typically used in DSSCs) immersed in a highly acidic iodolyte solution. The Ag metal electrode encapsulated by the PVA/PrGO film survived for over 500 hrs, superior to existing barriers of glass frits, epoxy resins and polymers. The PVA/PrGO film strongly adheres to the Ag metal surface, and the resulting PVA/PrGO/Ag electrode is stable even on a curved substrate, with a sheet resistance nearly independent of curvature. These results give new insight for the design of high-performance and solution-processable flexible liquid barrier films for a wide range of applications, in particular for the encapsulation of electronic devices with liquid electrolytes. PMID- 27263655 TI - Widely tunable Tm-doped mode-locked all-fiber laser. AB - We demonstrated a widely tunable Tm-doped mode-locked all-fiber laser, with the widest tunable range of 136 nm, from 1842 to 1978 nm. Nonlinear polarization evolution (NPE) technique is employed to enable mode-locking and the wavelength tunable operation. The widely tunable range attributes to the NPE-induced transmission modulation and bidirectional pumping mechanism. Such kind of tunable mode-locked laser can find various applications in optical communications, spectroscopy, time-resolved measurement, and among others. PMID- 27263656 TI - Thermal transport in bismuth telluride quintuple layer: mode-resolved phonon properties and substrate effects. AB - The successful exfoliation of atomically-thin bismuth telluride (Bi2Te3) quintuple layer (QL) attracts tremendous research interest in this strongly anharmonic quasi-two-dimensional material. The thermal transport properties of this material are not well understood, especially the mode-wise properties and when it is coupled with a substrate. In this work, we have performed molecular dynamics simulations and normal mode analysis to study the mode-resolved thermal transport in freestanding and supported Bi2Te3 QL. The detailed mode-wise phonon properties are calculated and the accumulated thermal conductivities with respect to phonon mean free path (MFP) are constructed. It is shown that 60% of the thermal transport is contributed by phonons with MFP longer than 20 nm. Coupling with a-SiO2 substrate leads to about 60% reduction of thermal conductivity. Through varying the interfacial coupling strength and the atomic mass of substrate, we also find that phonon in Bi2Te3 QL is more strongly scattered by interfacial potential and its transport process is less affected by the dynamics of substrate. Our study provides an in-depth understanding of heat transport in Bi2Te3 QL and is helpful in further tailoring its thermal property through nanostructuring. PMID- 27263657 TI - Spirochaetes dominate the microbial community associated with the red coral Corallium rubrum on a broad geographic scale. AB - Mass mortality events in populations of the iconic red coral Corallium rubrum have been related to seawater temperature anomalies that may have triggered microbial disease development. However, very little is known about the bacterial community associated with the red coral. We therefore aimed to provide insight into this species' bacterial assemblages using Illumina MiSeq sequencing of 16S rRNA gene amplicons generated from samples collected at five locations distributed across the western Mediterranean Sea. Twelve bacterial species were found to be consistently associated with the red coral, forming a core microbiome that accounted for 94.6% of the overall bacterial community. This core microbiome was particularly dominated by bacteria of the orders Spirochaetales and Oceanospirillales, in particular the ME2 family. Bacteria belonging to these orders have been implicated in nutrient cycling, including nitrogen, carbon and sulfur. While Oceanospirillales are common symbionts of marine invertebrates, our results identify members of the Spirochaetales as other important dominant symbiotic bacterial associates within Anthozoans. PMID- 27263658 TI - High-resolution biophysical analysis of the dynamics of nucleosome formation. AB - We describe a biophysical approach that enables changes in the structure of DNA to be followed during nucleosome formation in in vitro reconstitution with either the canonical "Widom" sequence or a judiciously mutated sequence. The rapid non perturbing photochemical analysis presented here provides 'snapshots' of the DNA configuration at any given moment in time during nucleosome formation under a very broad range of reaction conditions. Changes in DNA photochemical reactivity upon protein binding are interpreted as being mainly induced by alterations in individual base pair roll angles. The results strengthen the importance of the role of an initial (H3/H4)2 histone tetramer-DNA interaction and highlight the modulation of this early event by the DNA sequence. (H3/H4)2 binding precedes and dictates subsequent H2A/H2B-DNA interactions, which are less affected by the DNA sequence, leading to the final octameric nucleosome. Overall, our results provide a novel, exciting way to investigate those biophysical properties of DNA that constitute a crucial component in nucleosome formation and stabilization. PMID- 27263659 TI - Photoelectrochemical Immunosensor for Detection of Carcinoembryonic Antigen Based on 2D TiO2 Nanosheets and Carboxylated Graphitic Carbon Nitride. AB - Carcinoembryonic antigen (CEA) was used as the model, an ultrasensitive label free photoelectrochemical immunosensor was developed using 2D TiO2 nanosheets and carboxylated graphitic carbon nitride (g-C3N4) as photoactive materials and ascorbic acid as an efficient electron donor. 2D TiO2 nanosheets was sythsized by surfactant self-assembly method and proved to have higher photoelectrochemical signals than TiO2 nanoparticles. Firstly, carboxylated g-C3N4 could be attached to 2D TiO2 nanosheets through the bond formed between carboxyl group of carboxylated g-C3N4 and TiO2. And the photocurrent of g-C3N4/TiO2 drastically enhances compared to carboxylated g-C3N4 and TiO2. Then, antibody of CEA was bonded to TiO2 through the dentate bond formed between carboxyl group of anti-CEA and TiO2, leading to the decrease of the photocurrents. As proven by PEC experiments and electrochemical impedance spectroscopy (EIS) analysis, the fabrication process of the immunosensor is successful. Under the optimal conditions, the intensity decreased linearly with CEA concentration in the range of 0.01~10 ng/mL. The detection limit is 2.1 pg/mL. The work provides an effective method for the detection of tumor markers and can be extended for the application in food safety and environmental monitoring analysis. PMID- 27263660 TI - Imprinting superconducting vortex footsteps in a magnetic layer. AB - Local polarization of a magnetic layer, a well-known method for storing information, has found its place in numerous applications such as the popular magnetic drawing board toy or the widespread credit cards and computer hard drives. Here we experimentally show that a similar principle can be applied for imprinting the trajectory of quantum units of flux (vortices), travelling in a superconducting film (Nb), into a soft magnetic layer of permalloy (Py). In full analogy with the magnetic drawing board, vortices act as tiny magnetic scribers leaving a wake of polarized magnetic media in the Py board. The mutual interaction between superconducting vortices and ferromagnetic domains has been investigated by the magneto-optical imaging technique. For thick Py layers, the stripe magnetic domain pattern guides both the smooth magnetic flux penetration as well as the abrupt vortex avalanches in the Nb film. It is however in thin Py layers without stripe domains where superconducting vortices leave the clearest imprints of locally polarized magnetic moment along their paths. In all cases, we observe that the flux is delayed at the border of the magnetic layer. Our findings open the quest for optimizing magnetic recording of superconducting vortex trajectories. PMID- 27263661 TI - The formation of an ordered microporous aluminum-based material mediated by phthalic acid. AB - By using phthalic acid as a soft template, we showed that it was possible to prepare a microporous aluminum-based material when the precipitation of Al(3+) was properly controlled. We also identified that this microporous aluminum-based material could be promising for the removal of fluoride ions in water treatment. PMID- 27263662 TI - Silyl Radical Activation of Alkyl Halides in Metallaphotoredox Catalysis: A Unique Pathway for Cross-Electrophile Coupling. AB - A strategy for cross-electrophile coupling has been developed via the merger of photoredox and transition metal catalysis. In this report, we demonstrate the use of commercially available tris(trimethylsilyl)silane with metallaphotoredox catalysis to efficiently couple alkyl bromides with aryl or heteroaryl bromides in excellent yields. We hypothesize that a photocatalytically generated silyl radical species can perform halogen-atom abstraction to activate alkyl halides as nucleophilic cross-coupling partners. This protocol allows the use of mild yet robust conditions to construct Csp(3)-Csp(2) bonds generically via a unique cross coupling pathway. PMID- 27263663 TI - Growth of graphene on cylindrical copper conductors as an anticorrosion coating: a microscopic study. AB - We have successfully grown graphene film on the surface of cylindrical copper conductors by chemical vapour deposition. The quality and number of graphene layers have been investigated using Raman spectroscopy, Raman mapping and scanning electron microscopy, as a function of methane gas flow rate and of growth temperature. Transmission electron microscopy analysis has been performed to verify the number of graphene layers, confirming the results obtained by Raman spectroscopy. The results open up the possibility of using graphene as an anticorrosion coating for copper cables and earth grids. PMID- 27263664 TI - We need to optimize piperacillin-tazobactam dosing in critically ill patients-but how? PMID- 27263665 TI - Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro. AB - We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly [hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model. PMID- 27263666 TI - Non-viral liver disease burden in HIV-monoinfected individuals: a longitudinal observational retrospective cohort study. AB - Recent advances in antiviral therapy have improved outcomes in HIV-positive individuals co-infected with hepatitis B and C virus (HBV/HCV). Our aim was to assess prevalence and predictors of chronic liver disease (CLD) due to the metabolic syndrome (MS), alcohol and antiretrovirals (ARVs) use in HIV monoinfected individuals. This was a retrospective cohort study (2005-2012). HIV positive patients with negative HBV/HCV serology and at least two elevated alanine aminotransferase (ALT) levels six months apart were included. Data are presented as mean +/- SD or percentage. Despite negative viral serology, 27% (1047/3872) of HIV-positive individuals had persistently elevated ALT. Only 243 (23.2%) were investigated (by imaging in the majority, only 58 undergoing liver biopsy/transient elastography). CLD was identified in 66.2%, this being clinically significant in one in four individuals. Potential CLD risk factors were alcohol (44.2%), hepatotoxic ARVs (74.1%) and MS risk factors (68%) with 68.7% having >1 risk factor. On multivariate logistic regression analysis serum triglyceride (OR 1.482, 95% CI 1.053-2.086, p = .024) was the only independent predictor of CLD. Overall, 4.3% were referred to Hepatology services. In conclusion, less than 6% of HIV-monoinfected individuals with persistently elevated ALT undergo objective assessment of hepatic fibrosis. Despite non stringent criteria, some degree of non-viral CLD is identified in approximately two-thirds of those investigated, risk factors being synonymous with those for the MS. This increasing yet under-recognised non-viral CLD burden warrants timely recognition to prevent long-term morbidity and mortality. PMID- 27263735 TI - Parvovirus-B19 and hematologic disorders. AB - Parvovirus-B19 (PV-B19) is a member of Parvoviridae, which is one of the smallest DNA viruses. PV-B19-associated diseases usually serve as a good representation of the balance of virus, host response and the immune system. The diseases manifested with PV-B19 are erythema infectiosum, which is common in children, hydrops fetalis, transient pure red cell aplasia in patients with chronic hemolytic anemia, arthralgia - mostly observed in women, and chronic pure red cell aplasia in immunocompromised individuals. Cytopenia (bicytopenia, monocytopenia or pancytopenia) may also accompany the diseases mentioned above. On the other hand, there are many diseases, including neurologic, vasculitic, hepatic, rheumatoid, nephritic, autoimmune, myocardial, and others in which the mechanisms of the diseases are not clear, which may be associated with PV-B19. The virus may manifest with unexpected and unexplained clinical pictures and lead to misdiagnosis. Therefore, hematologic disorders in any unestablished clinical diagnosis should be investigated for PV-B19 infection. However, serologic examination for PV-B19 diagnosis is not sufficient in immunocompromised status. The virus can be determined with polymerase chain reaction (PCR) in the serum or tissue samples. Supportive therapy, blood transfusion and immunoglobulin are the conventional therapeutic interventions for PV-B19 today. Vaccination studies are under examination. PMID- 27263736 TI - Long-term culture-initiating cells (LTC-IC) produced from CD34+ cord blood cells with limiting dilution method. AB - OBJECTIVE: Even though much progress has been made in defining primitive hematologic cell phenotypes by using flow cytometry and clonogenic methods, the direct method for study of marrow repopulating cells still remains to be elusive. Long Term Culture-Initiating Cells (LTC-IC) are known as the most primitive human hematopoietic cells detectable by in vitro functional assays. METHODS: In this study, LTC-IC with limiting dilution assay was used to evaluate repopulating potential of cord blood stem cells. RESULTS: CD34 selections from cord blood were completed succesfully with magnetic beads (73,64%+/-9,12). The average incidence of week 5 LTC-IC was 1: 1966 CD34+ cells (range 1261-2906). CONCLUSION: We found that number of LTC-IC obtained from CD34+ cord blood cells were relatively low in numbers when compared to previously reported bone marrow CD34+ cells. This may be due to the lack of some transcription and growth factors along with some cytokines and chemokines released by accessory cells which are necessary for proliferation of cord blood progenitor/stem cells and it presents an area of interest for further studies. PMID- 27263667 TI - Sex and post-menopause hormone therapy effects on hippocampal volume and verbal memory. AB - Many studies suggest sex differences in memory and hippocampal size, and that hormone therapy (HT) may positively affect these measures in women; however, the parameters of HT use that most likely confer benefits are debated. We evaluated the impact of sex and postmenopausal HT use on verbal learning and memory and hippocampal size in 94 cognitively intact women and 49 men. Using analysis of covariance that controlled for age and education, women had better total word learning and delayed verbal memory performance than men. HT analyses showed that non-HT users performed similarly to men, while HT users performed better than men in Delayed Memory regardless of whether use was current or in the past. Women had larger hippocampal volumes than men regardless of whether they were HT users. Using univariate linear models, we assessed group differences in the predictive value of hippocampal volumes for verbal learning and memory. Hippocampal size significantly predicted memory performance for men and non-HT users, but not for HT users. This lack of relationship between hippocampal size and verbal learning and memory performance in HT users suggests HT use may impact memory through extra-hippocampal neural systems. PMID- 27263737 TI - The effect of heparin on the cell cycle in human B-lymphoblasts: An in vitro study. AB - OBJECTIVE: Heparin has been shown to be a strong inhibitor of the proliferation of several cell types. In this in vitro study, we investigated whether different heparin concentrations can affect the cell cycle of lymphoblasts in newly diagnosed acute lymphoblastic leukemia (ALL) patients. METHODS: Lymphoblasts were incubated in different heparin concentrations (0, 10, 20 U/ml), and the percentages of lymphoblasts in each phase of the cell cycle were simultaneously measured by flow cytometry at 0, 1, and 2 hours (h). RESULTS: The percentages of lymphoblasts at the G2/M and S phases were significantly increased in 20 U/ml heparin concentration at 1 h compared to 0 U/ml (without heparin) concentration. We demonstrated that heparin increases the percentages of lymphoblasts in the S and G2/M phases in a concentration- and time-dependent manner. CONCLUSION: It was shown that heparin expands the proliferation of lymphoblasts by increasing the transition to G2/M and S phases and the S-phase fraction ratio. Heparin thus appears promising for its contribution to new treatment fields such as by providing a synergistic effect with chemotherapeutic drugs. PMID- 27263738 TI - Autonomic nervous system dysfunction and serum levels of neurotoxic and neurotrophic cytokines in patients with cobalamin deficiency. AB - OBJECTIVE: The imbalance between neurotoxic cytokine tumor necrosis factor-alpha (TNF-alpha) and neurotrophic cytokines epidermal growth factor (EGF) and interleukin-6 (IL-6) plays a role in the pathogenesis of cobalamin (Cbl) deficiency-induced neuropathy. The aim of this study was to evaluate autonomic nervous system dysfunction and to look for any relationship between autonomic nervous system disturbances and serum cytokine levels (TNF-alpha, EGF, IL-6) in patients with Cbl deficiency. METHODS: Serum levels of TNF-alpha, EGF and IL-6 were studied in patients with Cbl deficiency (n=41) and a healthy control group (n=17) and after 3 months in patients who underwent Cbl replacement therapy (n=22). All patients with Cbl deficiency underwent electrophysiological studies (EPS) for the diagnosis of neuropathy. Statistical analysis was performed using SPSS for Windows 11.5 software. RESULTS: With EPS, 29 of 41 Cbl-deficient patients (70.73%) demonstrated neurological dysfunction [3 (7.32%), 19 (46.34%) and 7 (17.07%) patients with sensorimotor peripheral neuropathy, parasympathetic, and sympathetic autonomic dysfunction, respectively]. Although there was no significant difference in serum levels of EGF and IL-6 between patients with versus without autonomic dysfunction, levels were significantly lower in Cbl- deficient patients than healthy controls. CONCLUSION: Presence of autonomic dysfunction seems to be a frequent neurological finding in patients with Cbl deficiency. However, we could not find any relationship between serum cytokine levels and autonomic dysfunction by EPS. PMID- 27263739 TI - Clinical and laboratory data of primary hemophagocytic lymphohistiocytosis: A retrospective review of the Turkish Histiocyte Study Group. AB - OBJECTIVE: This study analyzes the clinical and laboratory findings of children with primary hemophagocytic lymphohistiocytosis (HLH) followed in various referral centers of Turkey. METHODS: A simple three-page questionnaire prepared by the Turkish Histiocyte Study Group was used for documentation of patient data. RESULTS: Age at diagnosis varied from 0.6 to 78 months (median+/-SD, 16.5+/ 26.1). Sex distribution was almost equal (F/M=10/12). The frequencies of parental consanguinity and sibling death in the family history were 100% and 81.1%, respectively. The most common clinical findings were hepatomegaly (100%) and fever (95%). The most common laboratory findings were anemia (100%), hyperferritinemia (100%) and thrombocytopenia (90.9%). Triglyceride and total bilirubin levels in the deceased versus surviving group appear to be high (triglyceride: 394+/-183 mg/dl, 289+/-7 mg/dl; total bilirubin: 2.7+/-6.9 mg/dl, 0.5+/-1.2 mg/dl, respectively). CONCLUSION: We concluded that fever, hepatosplenomegaly, anemia, thrombocytopenia, and hyperferritinemia are the most common clinical and laboratory findings in primary HLH. Increased triglyceride and total bilirubin level at the time of diagnosis might be an indicator of poor prognosis in HLH. PMID- 27263740 TI - The predictive value of stimulation index calculated by modified mixed lymphocyte culture in the detection of GVHD following hematopoietic stem cell transplantation. AB - OBJECTIVE: Mixed lymphocyte culture (MLC) is one of the routine tests performed prior to hematopoietic stem cell transplantation (HSCT) as a predictive assay for assessing the quality of donor matching and graft-versus-host disease (GVHD). The stimulation index is one of the formulas of the MLC test, and it is used for evaluation of matching between donor and recipient. Modified MLC (mMLC) test is produced by adding various cytokines to the MLC test, and increased sensitivity has been reported with this modification. METHODS: The importance of the stimulation index values in MLC and mMLC tests was evaluated in 59 patients who received HSCs from human leukocyte antigen-identical sibling donors. In the mMLC test, cytokines were added as interleukin (IL)-2, IL-2 + IL-4 and IL-2 + interferon (IFN)-gamma + tumor necrosis factor (TNF)-alpha. Stimulation index values in mMLC test were compared with stimulation index values in MLC test. RESULTS: Twenty-three (39%) patients developed GVHD. When evaluated in terms of stimulation index >1 patients, in MLC, 55% of the patients developed GVHD (p=0.229), whereas these values were 75% in the IL-2 added mMLC test (p=0.035), 100% in the IL-2 + IL-4 added mMLC test (p=0.076) and 85.7% in the IL-2 + IFN gamma + TNF-alpha added mMLC test (p=0.015). CONCLUSION: mMLC increased the sensitivity of the test. The relation between the positive results and evidence of GVHD after transplantation was found significant. PMID- 27263741 TI - The changes in complete blood count in thyroid cancer patients treated with radioactive iodine ablation therapy. AB - OBJECTIVE: The aim of this study was to evaluate the effect of radioactive iodine (RAI) ablation therapy on the complete blood count (CBC) in thyroid cancer patients. METHODS: One hundred sixty four patients undergoing RAI ablation therapy after total thyroidectomy were included. CBC results were available from the patients' medical records at the time of ablation and at the 1st, 6th, and 12th months after RAI therapy. RESULTS: Hemoglobin (Hb), white blood cell (WBC) and platelet (Plt) values were significantly lower than baseline at 1 month after treatment (p <0.0001). Hb and WBC values were increased at the 6th month and at the 1st year. Plt values increased at the 6th month but had decreased again at the 1st year. The values were usually in normal ranges except in the patients with low pretreatment Hb and WBC values. CONCLUSION: RAI ablation therapy in thyroid cancer patients is a safe treatment modality without any serious or persistent hematological side effects. PMID- 27263742 TI - Are university students a favorable target group for blood donation campaigns? AB - OBJECTIVE: The aim of this study was to investigate the willingness of university students regarding blood donation and to compare results among residents living in the Kayseri city center. METHODS: Admission for blood donation after donor acquisition campaigns and the rates of repeated donation over a one-year period were compared between the two groups. RESULTS: Between November 2006 and August 2008, a total of 29614 people were included in the study. After educational campaigns, the rate of admission for blood donation was 66% among university students, while it was only 29% among the city residents. Although the deferral rate and adverse events during donation were found to be higher in the student group, they had a higher repeated donation rate and higher return rate after a short message system. CONCLUSION: University students appear to be good candidates for long-term regular blood donation. Use of a short message system to issue reminders about blood donation may be a reasonable method to replenish the blood supply. PMID- 27263743 TI - Prognostic value of soluble angiopoietin-2 and soluble Tie-2 in Egyptian patients with acute myeloid leukemia. AB - OBJECTIVE: Angiogenesis plays a critical role in the development and growth of solid tumors and hematologic malignancies. The system involving angiopoietin-2 [Ang-2] and its receptor Tie-2 appears to play an important role in tumor angiogenesis and in the biology of hematological and non-hematological malignancies. We evaluated the levels of soluble (s)Ang-2 and sTie-2 in acute myeloid leukemia (AML) patients and investigated the impact of their circulating levels on the overall survival in those patients. METHODS: Ang-2 and Tie-2 were measured in plasma samples from AML patients and controls using enzyme-linked immunosorbent assay (ELISA). RESULTS: The levels of sAng-2 and sTie-2 were significantly higher in AML patients (2382.1+/-1586.1 pg/ml and 6.74+/-3.47 ng/ml, respectively) than in controls (649.5+/-402.6 pg/ml and 2.63+/-0.57 ng/ml, respectively; p<0.01). AML patients with high levels of sAng-2 and sTie-2 (>=2500 pg/ml and >=8 ng/ml, respectively) had significantly shorter overall survival than those patients with low levels (<2500 pg/ml and <8 ng/ml, respectively). CONCLUSION: The results of our study demonstrated the prognostic significance of circulating sAng-2 and sTie-2 in AML patients. Modulation of the angiopoietin / Tie-2 axis may be a promising approach to improve the outcome in those patients. PMID- 27263744 TI - Acquired pure megakaryocytic aplasia successfully treated with cyclosporine. AB - Acquired pure megakaryocytic aplasia is a rare hematological disorder characterized by thrombocytopenia with absent or markedly reduced megakaryocytes in the bone marrow. We report a case of a 25-year-old male diagnosed as acquired pure megakaryocytic aplasia. Treatment with prednisone and intravenous immunoglobulin failed, but he was successfully treated with cyclosporine, with complete remission after 90 days and normal platelet count maintained thereafter. PMID- 27263745 TI - Syngeneic peripheral blood stem cell transplantation with immunosuppression for hepatitis-associated severe aplastic anemia. AB - Hepatitis-associated aplastic anemia occurs in up to 10% of all aplastic anemia cases. Syngeneic bone marrow transplantation is rare in patients with severe aplastic anemia and usually requires pre-transplant conditioning to provide engraftment. We report on a 29-year-old male patient with hepatitis-associated severe aplastic anemia who had a series of severe infectious conditions before transplantation, including tracheal inflammation. Life-threatening bleeding, which developed after bronchoscopy, was successfully treated with activated recombinant factor VII and platelet transfusions. Syngeneic peripheral blood stem cell transplantation using immunosuppressive treatment with antithymocyte globulin and cyclosporin A without high-dose pre-transplant conditioning was performed, followed by complete hematologic and hepatic recovery. PMID- 27263746 TI - A case of acute lymphoblastic leukemia with additional chromosomes X and 5 associated with a Philadelphia chromosome in the bone marrow. AB - We report herein a very rare case of acute lymphoblastic leukemia having a chromosomal constitution of 48,XY,+X,+5,t(9;22)(q34;q11) in the bone marrow. A patient with additional chromosomes X and 5 with a Philadelphia chromosome has not been reported previously. However, no abnormal karyotype was obtained from the lymphocytes in our patient, and he did not have the characteristics of Klinefelter syndrome. He achieved a complete remission with IDA-FLAG and dasatinib therapy. The mechanism of trisomy 5 or any other chromosomal aneuploidy in the pathogenesis of leukemogenesis remains unclear. Further studies involving the genes affected by this karyotype and their products may lead to strategies to further increase the understanding of drug-resistant acute lymphoblastic leukemia and may represent the next frontier in the targeted therapy of those patients. PMID- 27263747 TI - Niemann - Pick disease associated with hemophagocytic syndrome. AB - Hemophagocytic lymphohistiocytosis (HLH) is a disease characterized by phagocytosis of blood cells by macrophages within the lymphoreticular tissue. It can develop secondary to some diseases or be familial as a result of genetic mutations. Niemann-Pick disease (NPD) is a very rare lipid storage disease. A three-month-old girl presented with high fever (39 degrees C), abdominal distension and paleness. The parents were consanguineous. The liver and spleen were palpable 10 cm and 11 cm below the costal margins, respectively. Bicytopenia (Hb: 5.5 g/dl, platelet: 77000/mm3), hypertriglyceridemia (351 mg/dl), hyperferritinemia (>1500 ng/dl) and hypofibrinogenemia (120 mg/dl) were detected. Bone marrow aspiration demonstrated foam cells and hemophagocytosis by macrophages and Niemann-Pick cells. Lysosomal sphingomyelinase activity was 0.24 nmol/h/mg/protein (normal: 0.86-2.8). Due to the parents' refusal of further evaluation, the nature of HLH as primary or secondary could not be determined. To the best of our knowledge, this is the first case of NPD associated with HLH and the first demonstration of hemophagocytosis by Niemann-Pick cells. PMID- 27263748 TI - Autoimmune hemolytic anemia and giant cell hepatitis: Report of three infants. AB - Giant cell hepatitis associated with direct Coombs' test-positive hemolytic anemia is a rare condition of childhood and the pathogenesis remains unclear. An autoimmune activation and loss of self-tolerance in these patients may be the underlying pathology related to the response of some of the patients to immunosuppressive treatment. Herein, we report the clinical presentation and course of three consecutive patients with this rare condition. We conclude that serum ferritin at diagnosis may be used for prediction of the outcome. PMID- 27263749 TI - Mega-dose methylprednisolone (MDMP) for chronic idiopathic myelofibrosis. PMID- 27263750 TI - Pancreatitis in a child with acute lymphoblastic leukemia after Erwinia asparaginase: Evaluation of ultrasonography and computerized tomography as diagnostic tools. PMID- 27263751 TI - Thrombosis and risk factors. PMID- 27263752 TI - Laboratory diagnosis of acute leukemia in Iraq, the available options. PMID- 27263753 TI - The incidence of alpha-thalassemia in Setif, Algeria. PMID- 27263754 TI - FDG-PET in mantle cell lymphoma involving skin. PMID- 27263755 TI - Spinal cord involvement of multiple myeloma detected by F-18 FDG PET/CT Scan. PMID- 27263756 TI - Use of early hard palate closure using a vomer flap in cleft lip and palate patients. AB - OBJECTIVES: The aim of the present study was to determine the influence of the vomer flap during cleft palate closure. MATERIALS AND METHODS: A retrospective review was performed of all consecutive unilateral/bilateral complete cleft lip and palate (Veau III en IV) children who were treated by a simultaneous lip and hard palate closure using a vomer flap. Data were collected for sex, date of birth, syndrome, adoption, cleft palate type, type of repair, date of cleft repair, cleft width, lateral incisions, fistula and location of fistula. RESULTS: Ninety-one children (M = 62, F 29) were operated. Mean age at time of lip closure and vomer flap was 5.8 months (range 2.9 months to 49.2 months, SD 7.1) and the mean age at palate closure was 13.6 months (range 6.3 months to 79.9 months, SD 10.8). The mean cleft width at first assessment was 13.0 mm (range 7-22 mm) compared to 8.8 mm (range 4-15 mm) at second assessment (mean difference 4.6 mm, 95% CI 3.93-5.35, p < 0.01). One patient developed a fistula (1.1%) and required secondary surgery for closure. CONCLUSION: The vomer flap leads to a substantial decrease in cleft width, subsequently leading to a low fistula incidence (1.1%). PMID- 27263757 TI - Fluorescence-guided surgery for the treatment of medication-related osteonecrosis of the jaw: A prospective cohort study. AB - INTRODUCTION: The delineation of the necrotic bone is a crucial step in the surgical treatment of medication-related osteonecrosis of the jaw (MRONJ). Several different approaches have been described including the innovative technique of fluorescence-guided surgery. However, until now there is a lack of data regarding the outcome. Therefore, the aim of the present study is to investigate the long-term success rates of fluorescence-guided surgery in the treatment of MRONJ. PATIENTS AND METHODS: 54 Patients were prospectively assigned for surgical treatment of medication-related osteonecrosis of the jaw using fluorescence-guided surgery. Patients received doxycycline 100 mg twice a day for at least seven days preoperatively. Surgical treatment of MRONJ included complete removal of necrotic bone, which was monitored using the visual enhanced lesion scope (Velscope), followed by smoothening sharp bony edges and meticulous wound closure. Procedure success was assessed as postoperative maintenance of full mucosal coverage without pain, infection or bone exposure during regular follow up. RESULTS: The study included a total of 54 patients (32 female and 22 male, mean age 71.4 +/- 9.2 years). In the last follow-up an intact mucosa and absence of exposed bone, pain or signs of infection was identified in 47 of 54 patients (87%) and 56 of 65 lesions (86.2%) after first surgery using fluorescence guidance. In 4 patients with 6 lesions a second fluorescence-guided surgery was necessary to achieve complete mucosal closure. Respectively, including the case with second surgical attempt 51 of 54 patients (94.4%) and 62 of 65 lesions (95.4%) showed complete mucosal healing. CONCLUSION: The study shows that fluorescence-guided surgery is a safe and successful treatment option which can be considered for all stages of MRONJ. The technique seems also promising for MRONJ cases under denosumab. PMID- 27263758 TI - Promoting Health for All Kansans Through Mass Media: Lessons Learned From a Pilot Assessment of Student Ebola Perceptions. AB - OBJECTIVE: We aimed to assess student knowledge of Ebola virus disease (EVD) and opinions about media coverage of EVD. METHODS: We conducted a pilot study with a cross-sectional survey and a convenience sample. RESULTS: Sixty-five college students participated in the survey and reported a low level of basic knowledge of EVD, high health literacy levels, and Internet and health professionals as sources for health information. CONCLUSION: This pilot study was an important first step to understanding students' knowledge of Ebola, common sources of health information, and health literacy levels. Results from this study highlight the need to improve health communication training and further evaluate the quality of health information dissemination via all communication sources. (Disaster Med Public Health Preparedness. 2016;10:641-643). PMID- 27263759 TI - Are Orthopaedic Systematic Reviews Overly Prevalent? AB - Systematic Reviews (SRs) are becoming an increasingly utilized resource for readers that aims to answer a specific question by critically analyzing multiple research studies or papers on a topic. Although an SR can be extremely helpful to find an answer to a question, it may also be scrutinized, as the methodology is often not robust enough to adequately determine the outcome. This editorial serves to highlight the benefits of an SR, the methodology of a high-caliber SR, and some common pitfalls that may reduce the impact of an SR. PMID- 27263760 TI - Regarding "Magnetic Resonance Imaging Currently Fails to Fully Evaluate the Biceps-Labrum Complex and Bicipital Tunnel". PMID- 27263761 TI - Editorial Commentary: The Larger Holes or Larger Number of Holes We Drill in the Coracoid, the Weaker the Coracoid Becomes. AB - The larger holes or larger number of holes we drill in the coracoid, the weaker the coracoid becomes. Thus, minimizing bone holes (both size and number) is required to lower risk of coracoid process fracture, in patients in whom transosseous shoulder acromioclavicular joint reconstruction is indicated. A single 2.4-mm-diameter tunnel drilled through both the clavicle and the coracoid lowers the risk of fracture, but the risk cannot be entirely eliminated. PMID- 27263762 TI - Editorial Commentary: Please Simplify Hip Arthroscopy. AB - Hip arthroscopy is a challenging technical procedure for which basic science principles have not been thoroughly discerned with respect to the procedures we perform. In this commentary, a plea is made to continue to expand the science behind what we do, but in as simple a fashion as possible such that more surgeons are willing to learn perfect hip arthroscopy. PMID- 27263763 TI - Editorial Commentary: Confirming Intuitive Thoughts in Hip Preservation. AB - In a biomechanical laboratory study of 63 bovine hip labra examining suture configuration, passer size, and radiofrequency treatment, superior biomechanical properties were found for vertical and oblique sutures compared with horizontal sutures, smaller puncture holes were better compared with large bore holes in the labra, and radiofrequency strengthened labra only when horizontal suture configuration was used. The authors appropriately acknowledge that suture anchor type, presence or absence of knots, and bone quality based on patient demographics and considering various regions of the acetabular rim are additional important factors. Although the authors wisely advocate caution in extrapolation to in vivo behavior, this study represents an important addition to our understanding of the importance of suture configuration in labral repair in the hip. Given the findings of this study and the present state of the art, the current winning formula appears to be labral base refixation with vertical or oblique mattress configuration, performed with small diameter suture passage devices. PMID- 27263764 TI - Editorial Commentary: The Pivot-Shift Phenomenon Is Multifactorial. AB - The biomechanical study on the role of the anterior cruciate ligament and anterolateral structures in controlling internal tibial rotation has some major limitations: creation of a large injury to the anterolateral structures, examination only at 30 degrees of flexion, only one outcome variable (internal rotation), and no application of different combined forces. This "worst-case scenario" does not represent the typical injury pattern, and therefore the results might overestimate the influence of these structures on rotatory laxity. Essentially, the pivot-shift phenomenon is multifactorial and injuries or insufficiency of the anterolateral structures are only one explanation. PMID- 27263766 TI - "Niche" concept and the hematopoietic stem cell niches. AB - A stem cell niche is defined as the most suitable tissue microenvironment where somatic cells (parent cells) or in some cases extracellular matrix elements and stem cells are present in an exclusive interaction. In recent years, promising data were published revealing the molecular and functional significance of cell cell contacts in stem cell proliferation (self-renewal) and differentiation into mature cells. In this brief review, recent progress has been documented with special emphasis on the structural-functional relationship between stem cells and surrounding cells. Hematopoietic stem cells and their niches are among the most studied stem cell types and cell-cell interactions, which have specific as well as some common properties observed in other niche sites in the human body. Some of the signaling pathways, which are illustrated by original drawings herein, obviously play major roles in stem cell self-renewal capacity and differentiation status. Therefore, stem cell niches stand as the most critical biological sites in stem cell physiology and could also be considered as the new targets for the treatment of certain diseases. PMID- 27263765 TI - Editorial Commentary: Iatrogenic Instability of the Hip: A Perfect Storm. AB - Iatrogenic instability of the hip is likely a perfect storm with enough factors coming together just wrong to create the problem. Capsular neglect is but one potential component. Instability is also just one of a myriad of problems that can be encountered following hip arthroscopy that ranges on a spectrum from too loose to too stiff with numerous reasons in between for incomplete pain relief and residual dysfunction. Proper capsular management does not always mean capsular repair. PMID- 27263767 TI - Red grape seed extract and its compound resveratrol exert cytotoxic effect to various human cancer lines. AB - Modern medicinal agents currently available for treatment of cancers are very expensive, toxic, and less effective in treating some of the disease. Thus, one must investigate further in detail the agents derived from natural sources, such as grape seed, for the prevention and treatment of cancer and disease. In recent years interest of researchers has focused on grape seed and nowadays scientists have used extracts of grape seed to treat different health problems including cancer. We examined the cytotoxic effect of red grape seed extract (GSE) and its main compound resveratrol (RES) on different human cancer cell lines representing various solid tumors and hematological malignancies at the same time. Red GSE was prepared by using 1, 1, 1, 2- Tetrafluoroethane extraction method. Cytotoxicity of the extract and RES was evaluated by using trypan blue dye exclusion method and MTT assay. The results of our study show that GSE and RES have cytotoxic activities in varying degree in several cancer cell lines. There has not been any study evaluating the GES and RES in the same cell lines and in the same conditions. But, it is still needed to have more pre-clinical and laboratory studies to validate the usefulness of these agents either alone or in combination with existing therapy. PMID- 27263768 TI - Thrombocytosis in the neonatal intensive care unit: Experience at a single center. AB - Although thrombocytosis is frequently detected in newborns, few reports have focused on its risk factors. This report documents the characteristics of 89 neonates with thrombocytosis followed up in a neonatal intensive care unit (NICU). We reviewed the patients' medical and laboratory records retrospectively to determine the associated conditions and risk factors for neonatal thrombocytosis, and complications related to thrombocytosis. We also discussed the differences of neonatal thrombocytosis from that of childhood in the light of literature. The mean platelet count of these newborns was 579.7 +/- 111.5 (451 936) x 109/L. Associated conditions included anemia (73.7%), high- isk pregnancies (56. %), prematurity (51.7%), infections (37.1%), antenatal drug use (22.7%), indirect hyperbilirubinemia (20.2%), cardiac disorders (14.6%), respiratory distress syndrome (14.6%), history of hypoxia (13.5%), surgery (12.4%), and hemorrhage (3.4%). In most cases, more than one risk factor for thrombocytosis existed in the same newborn. No hemorrhagic complications related to thrombocytosis were observed; however, 1 newborn had portal vein thrombosis associated with intestinal malrotation. In summary, risk factors and associated conditions for thrombocytosis in newborns differed from those in children. In light of associated disorders, the mechanism of thrombocytosis in newborns may differ from that of childhood thrombocytosis. PMID- 27263769 TI - The effect of granulocyte colony-stimulating factor on engraftment in patients with lymphoproliferative malignancies and solid tumors undergoing autologous peripheral stem cell transplantation. AB - The effects of granulocyte colony-stimulating factor (G-CSF) and engraftment quality on the rate of hematopoietic system recovery were assessed in patients with solid tumors and lymphoproliferative diseases after autologous hematopoietic stem cell ransplantation. Treatment with autologous hematopoietic stem cell transplantation was performed in 40 patients for non- Hodgkin's lymphoma (n= 20), Hodgkin's lymphoma (n= 8), multiple myeloma (n= 8), and breast cancer (n=4). In 20 patients with solid tumors and ymphoproliferative diseases, treatment with autologous hematopoietic stem cell transplantation was followed by G-CSF therapy (experimental group). Another 20 patients with solid tumors and lymphoproliferative diseases were treated with autologous hematopoietic stem cell transplantation without G-CSF therapy (control group). The two patient groups were matched for age, sex, diagnosis, number of chemotherapy courses, and engraftment quality (nucleated cells or CD34+ cells). The experimental group received G-CSF in a dose of 5 MUg/kg body weight subcutoneous from day 1 of autologous hematopoietic stem cell transplantation until leukocyte count increase to > 1.0 x 109/L over three consecutive days. Nonparametric tests (x2-test, median test, extended median test) were used in statistical analysis. The hematopoietic system showed rapid recovery. Leukocyte count > 1.0 x 109/L was recorded on median day 11 (range 8-21) in the experimental group vs median day 12 (range 9-16) in the control group; gra-nulocyte count > 0.5 x 109/L on median day 12 (range 8-23) vs day 14 (range 10-16) in the control group; and platelet count > 20 x 109/L on median day 13 (range 8-80) vs day 11 (range 7-15) in the control group. Differences between the two patient groups were not statistically significant. G-CSF therapy administered after autologous hematopoietic stem cell transplantation did not result in faster leukocyte, granulocyte or platelet recovery. The patients receiving a relatively lower number of cells showed the same rate of recovery as those who received a higher cell number. The number of CD34+ cells per kg body weight did not correlate with the rate of leukocyte, granulocyte or platelet recovery. PMID- 27263770 TI - Hypericium perforatum extract (St. John's Wort) and hypericin induce apoptosis in leukemic HL-60 cells by effecting h-TERT activity. AB - Hypericin is the main active component of Hypericium perforatum (St. John's Wort). Hypericin has been proven to have antitumoral effect in in vitro condition against solid tumors by deteriorating the mitochondrial functions. It has also anti-leukemic effect in in vitro conditions. However, there has not been any comparative study with hypericin and extract obtained from Hypericium perforatum L. In this study, it has been aimed to investigate the potential cytotoxic role of the extract obtained from Hypericium perforatum grown in Ege region on leukemic cell line, to compare the cytotoxic effects of both extract and hypericin in HL-60 cells, and to clarify the underlying mechanism(s) of this cytotoxicity. Hypericium perforatum extract was used in dilutions as 1/1000, 1/5000, 1/10.000, 1/50.000 and the IC50 value was found to be as 1/10.000 dilution. Hypericin was found to have cytotoxicity in HL-60 cells in time and dose dependent manner between the doses of 1nM to 100 MUM with IC50 dose of 0.5 MUM. Hypericin with the dose of 0.5 MUM had similar cytotoxicity pattern with the cytotoxicity curve obtained with 1/10000 diluted extract. Apoptosis as an underlying mechanism of this cytoxocity was shown in HL-60 cells after incubation with IC50 dose of hypericin which was more remarkable at 48th hours by using acridine orange/ethidium bromide dye method. Total RNA was isolated concomittantly and h-TERT mRNA expression was analyzed at Light Cycler Real-time online polymerase chain reaction and it was found that the mRNA expression was meaningfully decreased at 48th hour of incubation of cells with hypericin. According to results of this study, we have shown that hypericin, as main cytotoxic compound of Hypericium perforatum L, induces apoptosis in HL-60 cells via effecting h-TERT mRNA expression. PMID- 27263771 TI - Gallbladder infiltration in acute lymphoblastic leukemia. PMID- 27263772 TI - Deep vein thrombosis in a child with Down syndrome: A case report. AB - We report on the case of iliofemoral popliteal vein thrombosis in a child with Down syndrome who had surgery for a congenital heart defect. She was readmitted to our hospital because of gastroenteritis and generalized tonic-clonic seizures at age 14 months. On the second day of hospitalization, color Doppler ultrasonography revealed right iliofemoral and popliteal vein thrombosis. She was treated successfully with intravenous fluids and low-molecular-weight heparin. No predisposing factor other than dehydration could be found in the patient. We suggest that dehydration should be kept in mind as a cause of deep-vein thrombosis in patients with severe dehydration. PMID- 27263773 TI - Good tolerance of high dose cytosine arabinoside and methotrexate after severe myelosuppression secondary to intrathecal administration of the same agents. PMID- 27263774 TI - [Not Available]. PMID- 27263775 TI - Immune pathophysiology of acquired aplastic anemia. AB - Acquired aplastic anemia (AA) is a hematopoietic dyscrasia characterized by pancytopenia and bone marrow hypoplasia. AA is considered to be caused mainly by T-cell attacks on hematopoietic stem cells, as assumption based on good responses to T-cell specific immunosuppressive therapy (IST). Several markers, such as HLA DRB1(*)1501 and an increase in the percentage of paroxysmal nocturnal hemoglobinuria (PNH) phenotype cells, have been shown to represent the immune pathophysiology of AA. However, little is known about the pathogenesis of AA. This review article focuses on immune mechanisms underlying the development of AA and the roles of the aforementioned markers in the management of bone marrow failure. PMID- 27263776 TI - Cord blood transplantation in Japan. AB - Cord blood transplantation (CBT) has increasingly been used in Japan and the annual number of CBT now exceeds 1,200. The cumulative number of CBT reached 12,853 in 2015, accounting for almost 1/3 of total CBT performed worldwide. It is true that smaller body size and lower costs, as compared to western countries, have been advantages for Japanese people in using CB as graft alternative. In addition, several novel findings regarding serious issues following CBT have been obtained, which further enhanced the use of CB. First, several mechanisms of engraftment failure following CBT other than cell dose have been reported, such as the presence of donor-specific anti-HLA antibodies or the development of hemophagocytic syndrome. Second, unique profiles of infectious complications following CBT have been reported, such as higher incidences of early bacterial infections and HHV-6 encephalitis, as compared to those following bone marrow (BM)/peripheral blood (PB) transplants. Third, the incidence of disease relapse was comparable to those following BM/PB transplants. Novel pre-transplant conditioning regimens using intravenous busulfan have been investigated with promising results being obtained to date. A recent analysis of Japanese transplant registry data revealed similar survival following CBT to HLA-matched unrelated BM/PB transplants. PMID- 27263777 TI - Mechanism of action and determinants of sensitivity to the proteasome inhibitor bortezomib in multiple myeloma therapy. AB - Bortezomib (BTZ), a proteasome inhibitor, has been widely used for the treatment of multiple myeloma (MM), including newly diagnosed as well as relapsed and refractory cases, and is considered to be a key drug in the induction therapy for MM. However, the precise mechanism underlying the action of this agent has yet to be fully elucidated. Predicting sensitivity to BTZ treatment by using adequate biomarkers would aid in the development of individual targeted therapies for MM. Herein, by reviewing preclinical studies using MM cell lines and other investigations that have analyzed primary MM samples from patients, we describe in detail the induction of MM cell death by proteasome inhibition and the factors that regulate the sensitivity of the proteasome inhibitor BTZ in MM cells. PMID- 27263778 TI - Epigenetic regulation of cell adhesion-mediated drug resistance acquisition in multiple myeloma. AB - Elucidation of the epigenetic mechanisms underlying drug resistance may greatly contribute to the advancement of cancer therapies. In the present study, we identified trimethylation of histone H3 at lysine-27 (H3K27me3) as a critical histone modification for cell adhesion-mediated drug resistance (CAM-DR), which is the most important form of drug resistance in multiple myeloma. Cell adhesion counteracted drug-induced hypermethylation of H3K27 via inactivating phosphorylation of EZH2, leading to sustained expression of anti-apoptotic genes including IGF1, BCL2 and HIF1A. Inhibition of the IGF-1R/PI3K/Akt pathway reversed CAM-DR by promoting EZH2 dephosphorylation and H3K27 hypermethylation both in vitro and in refractory murine myeloma models. To our knowledge, this is the first demonstration of an epigenetic mechanism underlying CAM-DR and provides a rationale for the inclusion of kinase inhibitors counteracting EZH2 phosphorylation in combination chemotherapy aimed at increasing the therapeutic index. PMID- 27263779 TI - Discovery of the target for immunomodulatory drugs (IMiDs). AB - Half a century ago, the sedative thalidomide caused a serious drug disaster because of its teratogenicity and was withdrawn from the market. However, thalidomide, which has returned to the market, is now used for the treatment of leprosy and multiple myeloma (MM) under strict control. The mechanism of thalidomide action had been a long-standing question. We developed a new affinity bead technology and identified cereblon (CRBN) as a thalidomide-binding protein. We found that CRBN functions as a substrate receptor of an E3 cullin-Ring ligase complex 4 (CRL4) and is a primary target of thalidomide teratogenicity. Recently, new thalidomide derivatives, called immunomodulatory drugs (IMiDs), have been developed by Celgene. Among them, lenalidomide (Len) and pomalidomide (Pom) were shown to exert strong therapeutic effects against MM. It was found that Len and Pom both bind CRBN-CRL4 and recruit neomorphic substrates (Ikaros and Aiolos). More recently it was reported that casein kinase 1a (Ck1a) was identified as a substrate for CRBN-CRL4 in the presence of Len, but not Pom. Ck1a breakdown explains why Len is specifically effective for myelodysplastic syndrome with 5q deletion. It is now proposed that binding of IMiDs to CRBN appears to alter the substrate specificity of CRBN-CRL4. In this review, we introduce recent findings on IMiDs. PMID- 27263780 TI - Mechanisms of drug resistance and sensitivity concerning novel agents for multiple myeloma. AB - Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment. Novel treatments such as proteasome inhibitors and immunomodulatory agents significantly prolong both progression free survival and overall survival (OS) in patients with MM. However, recent clinical data have indicated that it is difficult to eradicate all MM clones even with the administration of such novel agents. To overcome drug resistance (DR), further investigation of the mechanism underlying DR is required, and strategies to up regulate, maintain, and restore drug sensitivity will become increasingly important in the clinical setting. The findings from basic research focusing on the microenvironment, genetic abnormalities, and signal transduction disturbances related to MM pathogenesis are excellent strategies for developing new agents. In addition, based on the improved OS over 10 years and the low continuation rate of standard therapy in frail patients, a stratified strategy has the potential to provide total therapy. PMID- 27263781 TI - Prognostic significance of pleural/pericardial effusion and treatment optimization of PMBL. AB - The optimal treatment strategy for primary mediastinal large B-cell lymphoma (PMBL) remains unknown. We retrospectively analyzed 345 patients with newly diagnosed PMBL to identify prognostic factors and optimal treatments. Focusing on patients treated with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP) (N=187), a higher International Prognostic Index (IPI) and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival (OS) in patients treated with R-CHOP without consolidative radiation therapy (RT) [IPI: hazard ratio (HR), 4.23; 95% confidence interval (CI), 1.48-12.13; P=0.007; effusion: HR, 4.93; 95% CI, 1.37 17.69; P=0.015]. Combined with IPI and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without RT, those with lower IPI and the absence of effusion comprised approximately onehalf of these patients and could be identified as curable [OS and progression free survival (PFS) at 4 years, 95% and 87%, respectively)] Taken together, our simple indicators of IPI and the presence of effusion could stratify patients with PMBL and thereby facilitate treatment selection. PMID- 27263782 TI - Identification of human erythroid lineage-committed progenitors. AB - Elucidating the developmental pathway leading to erythrocytes and being able to isolate their progenitors is crucial to understanding and treating disorders of red cell imbalance such as anemia, myelodysplastic syndrome, and polycythemia vera. Endoglin (CD105) is a key marker for purifying mouse erythroid lineage committed progenitors (EPs) from bone marrow. Herein, we show that human EPs can also be isolated from adult bone marrow. We identified three subfractions that possessed different expression patterns of CD105 and CD71 within the previously defined human megakaryocyte/erythrocyte progenitor (hMEP; Lineage CD34(+)CD38(+)IL-3Ralpha(-)CD45RA(-)) population. Both CD71(-)CD105(-) and CD71(+)CD105(-) MEPs, at least in vitro, retained bipotency for the megakaryocyte (MegK) and erythrocyte (E) lineages, although the latter sub-population had a differentiation potential skewed toward the E-lineage. Notably, the differentiation output of the CD71(+)CD105(+) subset of cells within the MEP population was completely restricted to the E-lineage with the loss of MegK potential; thus, we termed CD71(+)CD105(-) MEPs and CD71(+)CD105(+) cells as E biased MEPs (E-MEPs) and EPs, respectively. These previously unclassified populations may facilitate understanding of the molecular mechanisms governing human erythroid development and serve as potential therapeutic targets in disorders of the erythroid lineage. PMID- 27263783 TI - Efficacy and safety of denosumab in multiple myeloma. AB - We analyzed 11 patients with multiple myeloma (MM) treated using denosumab in our institute. The median age was 69 years (range, 54-76 years), and 7 patients were male. Seven patients had presented with newly diagnosed MM. Four patients were initially treated with zoledronic acid, which was then later switched to denosumab. The median number of injections was 15 (range, 1-27). No patients developed skeletal-related events (SRE) during denosumab treatment. Hypocalcemia was defined as serum calcium levels below the baseline in all patients. To prevent hypocalcemia, 8 patients were administered oral calcium. The first course of denosumab injections in 9 patients resulted in more marked decreases in serum calcium concentrations than subsequent courses. Two patients discontinued denosumab after osteonecrosis of the jaw (ONJ) was suspected, but squamous cell carcinoma was later identified in one of these cases. Denosumab might be effective and safe for preventing SRE. Cautionary measurement of serum calcium concentrations and prophylactic supplementation with oral calcium are warranted to avoid hypocalcemia after the first denosumab injection. The possibility of ONJ also merits attention. The clinical diagnosis of ONJ should be considered based on performing appropriate histological analyses. PMID- 27263784 TI - Development tuberculous meningitis during chemotherapy for CD5-positive diffuse large B-cell lymphoma. AB - The patient was a 62-year-old woman with CD5(+) diffuse large B-cell lymphoma. Treatment with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) was started. On the eleventh day of the third cycle, headache and low grade fever developed. Her consciousness gradually deteriorated. Seven days after symptom onset, she was brought to the emergency department of our hospital. Cerebrospinal fluid (CSF) analysis revealed a white blood cell count of 25/MUl, and a protein level of 188 mg/dl. Antibacterial and antiviral agents were administered based on a diagnosis of acute meningitis. She showed no improvement. We performed another lumbar puncture and intrathecal chemotherapy, a combination of methotrexate and dexamethasone, was administered because we suspected central nervous system involvement of lymphoma. She showed transient improvement. On day 12, we started the R-MPV regimen (rituximab, methotrexate, procarbazine, and vincristine). However, fever and disturbance of consciousness persisted. On day 20, we empirically started anti-tuberculosis treatment. Four days later, tubercle bacilli were confirmed by CSF culture after a 23-day incubation. We ultimately confirmed a diagnosis of tuberculous meningitis. Impaired cellular immunity in lymphoma patients increases the risk of tuberculosis. It is important to consider tuberculous meningitis in the differential diagnosis of a lymphoma patient presenting with meningitis. PMID- 27263785 TI - Diffuse large B-cell lymphoma recurring with zosteriform cutaneous lesions. AB - A 75-year-old woman presented with edema of the left leg in December 2012. On examination, there was a palpable 5-cm tumor in the left lower abdomen, and PET/CT showed lymphadenopathy of the tracheal, para-aortic, left iliac and inguinal regions with increased FDG uptake. We performed histopathological examination of the iliac lymph node and diagnosed diffuse large B-cell lymphoma (DLBCL), stage IIIA. The patient received 8 courses of R-CHOP chemotherapy and achieved a complete response. In April 2014, she noticed seven new painful erythematous vesicles <1 cm in size on the skin of the left lower abdominal region. Herpes zoster was suspected and valacyclovir was administered. However, this medication had no effect, and the vesicles enlarged and became nodular. Histopathological examination of one of the skin lesions revealed the infiltration of DLBCL and the diagnosis of zosteriform cutaneous recurrence of DLBCL was thus made. Skin lesions mimicking herpes zoster have been reported in certain types of hematological malignancies, and histopathological diagnosis should be performed in such cases. PMID- 27263786 TI - Chronic myeloid leukemia relapsing ten years after allogenic bone marrow transplantation. AB - A 58-year-old female was diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (CML) in blast crisis (BC) in 2004. The patient received imatinib, which quickly induced molecular remission, and subsequently underwent bone marrow transplantation (BMT) from an unrelated human leukocyte antigen (HLA) identical donor. The post-transplant clinical course was essentially uneventful. In 2014, ten years after the BMT, the patient was admitted to our hospital complaining of lymphadenopathy, and blasts were observed in peripheral blood. The patient was diagnosed as having a CML relapse in myeloid BC, with leukemic infiltration in lymph nodes, and was treated with dasatinib. Subsequently, pleural effusion developed and nilotinib was administered, which induced normal blood counts without blasts and partial cytogenetic remission, one month after administration. Six months after the relapse, this patient underwent a second BMT from an HLA-matched unrelated donor. Recent studies have demonstrated the cumulative incidence of CML relapse more than five years after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to be higher than in acute myeloid leukemia. Although rare, the possibility of late relapse should be considered in patients diagnosed with CML after allo-HSCT. PMID- 27263787 TI - Achievement of hemodialysis discontinuation with lenalidomide and dexamethasone therapy in a refractory BJP-type multiple myeloma patient. AB - A 63-year-old man with Bence Jones-kappa multiple myeloma (MM) presented with renal impairment. First, we administered a bortezomib-containing regimen which is considered to be the first choice among therapeutic approaches for MM patients with renal failure. However, his condition was refractory to bortezomib, and the renal dysfunction worsened (creatinine 12.55mg/dl) necessitating the initiation of hemodialysis. Subsequently, we administered an adjusted dose of lenalidomide and dexamethasone. Dialysis could be discontinued after 3 cycles of lenalidomide therapy. After 4 cycles, he achieved a stringent complete response (sCR) with the creatinine level at 1.85mg/dl. This case suggests lenalidomide to be an effective drug for patients with multiple myeloma and renal impairment refractory to treatment with bortezomib. PMID- 27263788 TI - Reversible dasatinib-related pulmonary arterial hypertension in a CML patient. AB - A 59-year-old man diagnosed with the chronic phase of chronic myeloid leukemia (CML) in June 2011 was started on dasatinib (100 mg/day). He had no signs of pleural effusion (PE) or right heart failure before treatment, but symptoms of PE and dyspnea (New York Heart Association class III) appeared in January 2013 and May 2014, respectively. Doppler transthoracic echocardiography and right heart catheterization revealed pulmonary arterial hypertension (PAH) with an estimated pulmonary artery systolic pressure (PASP) of 80 mmHg and estimated mean pulmonary artery pressure of 29 mmHg. Rheumatoid factor, antinuclear antibody, dsDNA antibody, and SCL70 were not elevated, and computed tomography confirmed the absence of a pulmonary embolism. Therefore, dasatinib-related PAH was diagnosed and treatment with this agent was discontinued. The PASP had decreased to 51 and 40 mmHg at one month and one year, respectively, after dasatinib discontinuation. This patient developed PAH while receiving dasatinib administration and only discontinuation of this agent improved his symptoms. The possibility that dasatinib can cause PAH must be considered before administering this agent to patients with CML. PMID- 27263790 TI - Multiple myeloma developing in a patient with immune thrombocytopenia. AB - A female diagnosed as having immune thrombocytopenic purpura (ITP) was found to be simultaneously suffering from monoclonal gammopathy of undetermined significance (IgGlambda). Urine Bence-Jones protein was negative. During the course, plasma cells accounted for 21.6% of the bone marrow. Based on these clinical features in our case, the second disease was diagnosed as multiple myeloma (MM). Both ITP and MM were successfully treated with corticosteroids, bortezomib, lenalidomide with dexamethasone and eltrombopag olamine. MM with ITP may show the following features: 1) the great majority are IgG types, 2) lambda chain types show marked light chain predominance when these two diseases appear simultaneously, 3) kappa chain types are predominant in the cases with MM followed by ITP, and 4) MM cases with ITP are more often seen in Japan. PMID- 27263789 TI - Chronic active Epstein-Barr virus infection with marked pericardial effusion successfully treated with allogeneic peripheral blood stem cell transplantation. AB - A 23-year-old woman presented with a persistent fever and shortness of breath. Computed tomography showed marked pericardial effusion, hepatosplenomegaly, and cervical and mediastinal lymph node swelling. Epstein-Barr virus (EBV) antibody titers were abnormally elevated, and the copy number of EBV-DNA was increased in peripheral blood. Based on these observations, she was diagnosed with chronic active EBV infection (CAEBV). The EBV-infected cells in her peripheral blood were CD4(+)T lymphocytes. Fever and pericardial effusion improved following treatment with a combination of prednisolone, etoposide, and cyclosporine; however, peripheral blood EBV-DNA levels remained high. The patient underwent allogeneic peripheral blood stem cell transplantation from an EBV-seronegative, HLA-matched sibling donor, with fludarabine and melphalan conditioning. The post transplantation course was uneventful, except for mild skin acute graft-versus host disease (grade 2). EBV-DNA became undetectable in peripheral blood 98 days post transplantation. She has since been in good health without disease recurrence. CAEBV is a potentially fatal disease caused by persistent EBV infection of T lymphocytes or natural killer cells, thus requiring prompt treatment and allogeneic transplantation. Pericardial effusion is rarely observed in CAEBV and can impede its diagnosis. Therefore, we should be aware that patients may present with marked pericardial effusion as an initial manifestation of CAEBV. PMID- 27263791 TI - ALK-negative anaplastic large cell lymphoma with loss of CD30 expression during treatment with brentuximab vedotin. AB - A 59-year-old woman with anaplastic large cell lymphoma (ALCL), ALK-negative, was treated with brentuximab vedotin (BV) against relapse after 6 regimens of systemic chemotherapy and radiation. Despite achieving an initial response, skin lesions worsened after 11 courses. A skin biopsy after the development of resistance to BV confirmed loss of CD30 expression by the tumor cells, suggesting a possible cause of resistance. This case shows that down-regulation of CD30 does occur during BV treatment, resulting in resistance to this drug. Because of this possibility, in the future, expression of CD30 should be carefully monitored with extended use of BV against ALCL. PMID- 27263793 TI - [Not Available]. PMID- 27263792 TI - Development of myelofibrosis during eltrombopag treatment in a patient with immune thrombocytopenia. AB - Eltrombopag, a thrombopoietin (TPO) receptor agonist, is effective for treating refractory immune thrombocytopenia (ITP). However, the development of bone marrow fibrosis is a concern. A 78-year-old man was diagnosed with ITP in 2004. His platelet count did not increase after eltrombopag treatment initiation in 2014. However, anemia progressed, along with the presence of immature myelocytes, erythroblasts, and tear drop cells. At 8 months after initiating eltrombopag treatment, the patient underwent a bone marrow biopsy that showed grade 2 myelofibrosis. Hence, eltrombopag was discontinued. In our experience with this case indicates that careful observation is required while using TPO receptor agonists. PMID- 27263794 TI - Bacterial contamination of water samples in Gabon, 2013. AB - Contamination of water is a major burden in the public health setting of developing countries. We therefore assessed the quality of water samples in Gabon in 2013. The main findings were a contamination rate with coliforms of 13.5% and the detection of a possible environmental reservoir for extended spectrum beta lactamase-producing bacteria. PMID- 27263795 TI - Evaluating a Hospitalist-Based Intervention to Decrease Unnecessary Antimicrobial Use in Patients With Asymptomatic Bacteriuria. AB - OBJECTIVE Inappropriate treatment of asymptomatic bacteriuria (ASB) in the hospital setting is common. We sought to evaluate the treatment rate of ASB at the 3 hospitals and assess the impact of a hospitalist-focused improvement intervention. DESIGN Prospective, interventional trial. SETTING Two community hospitals and a tertiary-care academic center. PATIENTS Adult patients with a positive urine culture admitted to hospitalist services were included in this study. Exclusions included pregnancy, intensive care unit admission, history of a major urinary procedure, and actively being treated for a urinary tract infection (UTI) at the time of admission or >48 hours prior to urine collection. INTERVENTIONS An educational intervention using a pocket card was implemented at all sites followed by a pharmacist-based intervention at the academic center. Medical records of the first 50 eligible patients at each site were reviewed at baseline and after each intervention for signs and symptoms of UTI, microbiological results, antimicrobials used, and duration of treatment for positive urine cultures. Diagnosis of ASB was determined through adjudication by 2 hospitalists and 2 infectious diseases physicians. RESULTS Treatment rates of ASB decreased (23.5%; P=.001) after the educational intervention. Reductions in treatment rates for ASB differed by site and were greatest in patients without classic signs and symptoms of UTI (34.1%; P<.001) or urinary catheters (31.2%; P<.001). The pharmacist-based intervention was most effective at reducing ASB treatment rates in catheterized patients. CONCLUSIONS A hospitalist-focused educational intervention significantly reduced ASB treatment rates. The impact varied across sites and by patient characteristics, suggesting that a tailored approach may be useful. Infect Control Hosp Epidemiol 2016;37:1044-1051. PMID- 27263796 TI - Unconventional supercapacitors from nanocarbon-based electrode materials to device configurations. AB - As energy storage devices, supercapacitors that are also called electrochemical capacitors possess high power density, excellent reversibility and long cycle life. The recent boom in electronic devices with different functions in transparent LED displays, stretchable electronic systems and artificial skin has increased the demand for supercapacitors to move towards light, thin, integrated macro- and micro-devices with transparent, flexible, stretchable, compressible and/or wearable abilities. The successful fabrication of such supercapacitors depends mainly on the preparation of innovative electrode materials and the design of unconventional supercapacitor configurations. Tremendous research efforts have been recently made to design and construct innovative nanocarbon based electrode materials and supercapacitors with unconventional configurations. We review here recent developments in supercapacitors from nanocarbon-based electrode materials to device configurations. The advances in nanocarbon-based electrode materials mainly include the assembly technologies of macroscopic nanostructured electrodes with different dimensions of carbon nanotubes/nanofibers, graphene, mesoporous carbon, activated carbon, and their composites. The electrodes with macroscopic nanostructured carbon-based materials overcome the issues of low conductivity, poor mechanical properties, and limited dimensions that are faced by conventional methods. The configurational design of advanced supercapacitor devices is presented with six types of unconventional supercapacitor devices: flexible, micro-, stretchable, compressible, transparent and fiber supercapacitors. Such supercapacitors display unique configurations and excellent electrochemical performance at different states such as bending, stretching, compressing and/or folding. For example, all-solid-state simplified supercapacitors that are based on nanostructured graphene composite paper are able to maintain 95% of the original capacity at a 180 degrees folding state. The progress made so far will guide further developments in the structural design of nanocarbon-based electrode materials and the configurational diversity of supercapacitor devices. Future developments and prospects in the controllable assembly of macroscopic nanostructured electrodes and the innovation of unconventional supercapacitor configurations are also discussed. This should shed light on the R&D of supercapacitors. PMID- 27263797 TI - Ni(ii)/Cu(ii)/Zn(ii) 5,5-diethylbarbiturate complexes with 1,10-phenanthroline and 2,2'-dipyridylamine: synthesis, structures, DNA/BSA binding, nuclease activity, molecular docking, cellular uptake, cytotoxicity and the mode of cell death. AB - New 5,5-diethylbarbiturate (barb) complexes of Ni(ii), Cu(ii) and Zn(ii) with 1,10-phenanthroline (phen) and 2,2'-dipyridylamine (dpya), namely [Ni(phen kappaN,N')3]Cl(barb).7H2O (), [Cu(barb-kappaN)(barb-kappa(2)N,O)(phen kappaN,N')].H2O (), [Cu(barb-kappaN)2(phen-kappaN,N')] (), [Zn(barb-kappaN)2(phen kappaN,N')].H2O (), [Ni(barb-kappa(2)N,O)(dpya-kappaN,N')2]Cl.2H2O (), [Cu(barb kappa(2)N,O)2(dpya-kappaN,N')].2H2O () and [Zn(barb-kappaN)2(dpya-kappaN,N')] (), were synthesized and characterized by elemental analysis, UV-vis, FT-IR and ESI MS. The structures of the complexes were determined by X-ray crystallography. Notably, and were fluorescent in MeOH : H2O at rt. The interaction of the complexes with fish sperm (FS) DNA and bovine serum albumin (BSA) was investigated in detail by various techniques. The complexes exhibited groove binding along with a partial intercalative interaction with DNA, while the hydrogen bonding and hydrophobic interactions played a major role in binding to BSA. It is noteworthy that exhibited the highest affinity towards DNA and BSA. Enzyme inhibition assay showed that show a preference for both A/T and G/C rich sequences in pUC19 DNA, while and display a binding specificity to the G/C and A/T rich regions, respectively. These findings were further supported by molecular docking. The cellular uptake studies suggested that was deposited mostly in the membrane fraction of the cells. Among the present complexes, exhibited a very strong cytotoxic effect on A549, MCF-7, HT-29 and DU-145 cancer cells, being more potent than cisplatin. Moreover, induces cell death through the apoptotic mode obtained by flow cytometry. PMID- 27263798 TI - Sequential interventional treatment of right-sided lung cancer with complete lung atelectasis: A case report. PMID- 27263799 TI - Corrigendum to "beta-Adrenergic receptors couple to CFTR chloride channels of intercalated mitochondria-rich cells in the heterocellular toad skin epithelium" [Biochim. Biophy. Acta 1618 (2003) 140-152]. PMID- 27263801 TI - Strain-induced spin crossover and spin-polarized currents in a prototype graphene nanoribbon. AB - Graphene nanoribbons with well defined edges have been shown to possess high conductivities and behave like a quantum wire. Methods from synthetic organic chemistry have successfully been applied to produce such nanoribbons with smooth and chemically stable edges by saturation with hydrogen. Herein, we present ab initio calculations in a family of molecules related to the thinnest graphene nanoribbon, substitutionally doped with sulfur, for which synthetic methods are available. We show that sulfur doping can suppress the polyradical nature of these molecules. A strain-induced transition to a magnetic state is predicted for some of the studied molecules, at elongations as low as 1 A. The transport properties were calculated using the Landauer-Imry elastic scattering theory. It is shown that in the strain-induced magnetic state, the molecular conductance associated with the minority spins is three orders of magnitude larger than that of the majority of the spins, thus providing evidence of a graphene nanoribbon spin filter. PMID- 27263803 TI - A healthy female with C3 hypocomplementemia and C3 Nephritic Factor. PMID- 27263802 TI - An evaluation of health care expenditures in Crohn's disease using the United States Medical Expenditure Panel Survey from 2003 to 2013. AB - BACKGROUND: Previous estimates of the economic burden of Crohn's disease (CD) varied widely from $2.0 to $18.2 billion per year (adjusted to 2015 $US). However, these estimates do not reflect recent changes in pharmaceutical treatment options and guidelines. OBJECTIVE: The goal of this study was to update cost estimates of Crohn's disease based on a representative sample of the US population from the most recent 11 years (2003-2013) of the Medical Expenditure Panel Survey (MEPS). A secondary aim described expenditure trends in respondents with and without Crohn's disease pre-post FDA approvals of new biologics and the American College of Gastroenterology Crohn's disease treatment guidelines. METHODS: Average annual expenditures (total, prescription, inpatient, and outpatient) were evaluated using a pooled cross-sectional design. Respondent data from the most recent 11 years (2003-2013) of MEPS were analyzed. Two-part generalized linear models with power-link were used to estimate the average annual expenditures per patient adjusted to multiple covariates. Confidence intervals (CI) were estimated using bootstrap methods. Difference-in-differences estimations were performed to compare the changes in health care expenditures pre post FDA approvals of new biologics and the American College of Gastroenterology Crohn's disease treatment guidelines. RESULTS: The annual aggregate economic burden of CD was $6.3 billion in the US. Respondents with CD had higher total (+$6442; 95% CI: $4864 to $8297), prescription (+$3283; 95% CI: $2289 to $4445), inpatient (+$1764; 95% CI: $748 to $3551), and outpatient (+$1191; 95% CI: $592 to $2160) expenditures compared to respondents without CD. In the difference-in differences estimation, respondents with CD had significantly higher total (P = 0.001) and prescription (P < 0.001) expenditures compared with respondents without CD. Although inpatient and outpatient expenditures were higher in respondents with CD, they were not statistically significant. CONCLUSIONS: Respondents with CD diagnosis had higher expenditures compared to respondents without CD diagnosis from 2003 to 2013. This study captured the most recent availability of new treatment options and changes to treatment guidelines, while providing updated estimates of the economic burden of CD in the US. However, this research was unable to study the causes of these increased health care expenditures in respondents with CD. Future investigations will need to determine the causal factors for increased expenditures in CD. PMID- 27263804 TI - Cytokine profile in adult-onset Still's disease: Comparison with systemic juvenile idiopathic arthritis. AB - To compare pro-inflammatory cytokine profiles and kinetics in patients with adult onset Still's disease (AOSD) to those in patients with systemic juvenile idiopathic arthritis (s-JIA), we analyzed serum cytokine concentrations in 33 patients with AOSD and 77 patients with s-JIA and compared them with clinical features. Patients with AOSD and s-JIA shared a common cytokine profile pattern of a significant increase in IL-18. Patients with AOSD were classified into two subgroups based on serum IL-6 and IL-18 levels. The number of patients with arthritis was significantly higher in the IL-6-dominant subgroup. The cytokine patterns associated with s-JIA and AOSD share common features, such as a significant and predominant increase in IL-18. Distinct IL-6- and IL-18-based cytokine profiles might be responsible for distinct clinical manifestations. The presence of two distinct subgroups in patients with both diseases further supports the view that s-JIA and AOSD share a disease category. PMID- 27263805 TI - Enhanced quantum efficiency from a mosaic of two dimensional MoS2 formed onto aminosilane functionalised substrates. AB - Developing scalable methods of growing two dimensional molybdenum disulphide (2D MoS2) with strong optical properties, on any desired substrates, is a necessary step towards industrial uptake of this material for optical applications. In this study, Si/SiO2 substrates were functionalised using self-assembled monolayers of three different aminosilanes with various numbers of amine groups and molecular lengths as underlayers for enhancing the adherence of the molybdenum precursor. The tetrahedral [MoS4](2-) anion groups from the molybdenum precursor were bonded on these silanised Si/SiO2 substrates afterwards. The substrates were then treated with a combined thermolysis and sulphurisation step. The results showed that silanisation of the substrates using the longest chains and the largest number of amine groups provided a good foundation to grow quasi 2D MoS2 made from adjacent flakes in a mosaic formation. Microscopy and spectroscopy investigations revealed that these quasi 2D MoS2 formed using this long chain aminosilane resulted in flakes with lateral dimensions in micron and submicron ranges composed of adjoining MoS2 pieces of 20 to 60 nm in lateral dimensions, dominantly made of 3 to 5 MoS2 fundamental layers. The obtained quasi 2D MoS2 shows a high internal quantum efficiency of 2.6% associated with the quantum confinement effect and high stoichiometry of the adjoining nanoflakes that form the structure of the sheets. The synthesis technique in this study is reliable and facile and offers a procedure to form large, scalable and patternable quasi 2D MoS2 sheets on various substrates with enhanced optical properties for practical applications. PMID- 27263806 TI - Heterologous expression of five disulfide-bonded insecticidal spider peptides. AB - The genes of the five disulfide-bonded peptide toxins 1 and 2 (named Oxytoxins or Oxotoxins) from the spider Oxyopes lineatus were cloned into the expression vector pQE30 containing a 6His-tag and a Factor Xa proteolytic cleavage region. These two recombinant vectors were transfected into Escherichia coli BL21 cells and expressed under induction with isopropyl thiogalactoside (IPTG). The product of each gene was named HisrOxyTx1 or HisrOxyTx2, and the protein expression was ca 14 and 6 mg/L of culture medium, respectively. Either recombinant toxin HisrOxyTx1 or HisrOxyTx2 were found exclusively in inclusion bodies, which were solubilized using a chaotropic agent, and then, purified using affinity chromatography and reverse-phase HPLC (RP-HPLC). The HisrOxyTx1 and HisrOxyTx2 products, obtained from the affinity chromatographic step, showed several peptide fractions having the same molecular mass of 9913.1 and 8030.1 Da, respectively, indicating that both HisrOxyTx1 and HisrOxyTx2 were oxidized forming several distinct disulfide bridge arrangements. The isoforms of both HisrOxyTx1 and HisrOxyTx2 after DTT reduction eluted from the column as a single protein component of 9923 and 8040 Da, respectively. In vitro folding of either HisrOxyTx1 or HisrOxyTx2 yielded single oxidized components, which were cleaved independently by the proteolytic enzyme Factor Xa to give the recombinant peptides rOxyTx1 and rOxyTx2. The experimental molecular masses of rOxyTx1 and rOxyTx2 were 8059.0 and 6176.4 Da, respectively, which agree with their expected theoretical masses. The recombinant peptides rOxyTx1 and rOxyTx2 showed lower but comparable toxicity to the native toxins when injected into lepidopteran larvae; furthermore, rOxyTx1 was able to inhibit calcium ion currents on dorsal unpaired median (DUM) neurons from Periplaneta americana. PMID- 27263807 TI - Impact of computerized pre-authorization of broad spectrum antibiotics in Pseudomonas aeruginosa at a children's hospital in Japan. AB - BACKGROUND: The spread of antimicrobial-resistant organisms is a global concern. To stem this tide, an antimicrobial stewardship program at hospitals is essential to optimize the prescription of broad spectrum antibiotics. In this study we examined the impact of computerized pre-authorization for broad spectrum antibiotics for Pseudomonas aeruginosa at a children's hospital. METHODS: An antimicrobial stewardship program at Tokyo Metropolitan Children's Medical Center was assessed between March 2010 and March 2015. A paper-based post-prescription audit was switched to computerized pre-authorization for broad antipseudomonal agents in October 2011. The prescriber was required to obtain approval from physicians in the pediatric infectious diseases division before prescribing restricted antimicrobial agents. Approved prescriptions were processed and logged electronically. We evaluated days of therapy per 1000 patient-days, the cost of antibiotics, and the susceptibility of P. aeruginosa to piperacillin, ceftazidime, cefepime, piperacillin/tazobactam, carbapenems, and ciprofloxacin. Also, the average length of admission and infection-related mortality at 30 days were compared pre- and post-intervention. RESULTS: Administration of carbapenems, piperacillin/tazobactam, and ceftazidime decreased significantly after the introduction of computerized pre-authorization. Antibiotic costs were reduced by JPY2.86 million (USD 26,000) annually. None of the antipseudomonal agents showed decreased sensitivity. The average length of admission was shorter in post intervention. Infection-related mortality at 30 days showed no difference between the pre- and post-intervention periods. CONCLUSION: An antimicrobial stewardship program using computerized pre-authorization decreased the use and cost of broad spectrum antibiotics without significant difference in infection-related mortality at 30 days, although our study did not improve susceptibilities of P. aeruginosa. PMID- 27263808 TI - Cardiac Mass, Aortic Intramural Hematoma, and IgG4-related Disease: A Case Report. AB - As a designated entity within medicine, immunoglobulin G4 (IgG4)-related disease is relatively new. It is immune-mediated origin, characterized by a tendency for formation of tumefactive lesions, the infiltration of IgG4-positive plasma cells, and frequent but not invariable elevations of IgG4 levels in the serum. IgG4 related cardiac mass accompanying aortic intramural hematoma is an extremely rare clinical presentation. Herein we present the case of a patient who was admitted to our department complaining of severe chest pain. Computed tomographic angiography examination revealed a cardiac mass accompanying an aortic intramural hematoma. He underwent a surgical resection of the cardiac mass and a replacement of the ascending aorta with Hemashield Platinum graft and made an uneventful recovery. A diagnosis of an IgG4-related disease was made based on laboratory results and pathological examination. Corticosteroids were administered postoperatively. This case shows that the heart itself can also be a potential site for IgG4-related disease. PMID- 27263809 TI - Recurrent Brachiocephalic Vein Stenosis as a Cause for Persistent Left-sided Transudative Pleural Effusion in a Hemodialysis Patient. AB - BACKGROUND: Effusion is common in dialysis patients. The most common causes include fluid overload due to renal failure and nonrenal causes like congestive heart failure and infection. We here report a case of left side transudative effusion due to brachiocephalic venous stenosis. METHODS: A 34-year-old female who had chronic kidney disease V during transplant work-up was found to be having left arm swelling and left transudative effusion. Work-up for transudative effusion did not show any cardiac cause or liver problem. Her dialysis duration was optimized from 2 times a week to 3 times a week for 4 hr and her dry weight was adjusted. Despite adequate dialysis for 1 month, effusion on the left side persisted. She had a previous venoplasty for a stenosis in brachiocephalic vein but restenosis occurred again. RESULTS: Brachiocephalic vein stenting was performed which successfully lead to resolution of left arm swelling and left effusion. She was later on successfully transplanted. CONCLUSIONS: Brachiocephalic stenosis can cause ipsilateral transudative effusion. Venoplasty and stenting of the brachiocephalic vein lead to complete resolution of effusion. PMID- 27263810 TI - Preoperative Frailty Increases Risk of Nonhome Discharge after Elective Vascular Surgery in Home-Dwelling Patients. AB - BACKGROUND: Patient-centered quality outcomes such as disposition after surgery are increasingly being scrutinized. Preoperative factors predictive of nonhome discharge (DC) may identify at-risk patients for targeted interventions. This study examines the association among preoperative risk factors, frailty, and nonhome DC after elective vascular surgery procedures in patients living at home. METHODS: The 2011-2012 National Surgical Quality Improvement Project database was queried to identify all home-dwelling patients who underwent elective vascular procedures (endovascular and open aortic aneurysm repair, suprainguinal and infrainguinal bypasses, peripheral endovascular interventions, carotid endarterectomy, and stent). Preoperative frailty was measured using the modified frailty index (mFI; derived from Canadian Study of Health and Aging). Univariate and multivariate logistic regression analysis was performed to examine the association of frailty and nonhome DC. RESULTS: Of 15,843 home-dwelling patients, 1,177 patients (7.4%) did not return home postoperatively. Frailty (mFI > 0.25) conferred a significantly increased 2-fold risk of nonhome DC disposition for each procedure type. Frailty, female gender, open procedures, increasing age, end stage renal disease, and occurrence of any postoperative complication were associated with increased risk of nonhome DC. On multivariate logistic regression analysis, frailty increased the odds of nonhome DC by 60% (odds ratio 1.6, 95% confidence interval 1.4-1.8) after adjusting for other covariates. In the presence of complications, the risk of nonhome DC was 27.5% in frail versus 16.5% in nonfrail patients (P < 0.001). In the absence of complications, although absolute risk was lower, frail patients were nearly twice as likely to not return home (frail 5.5% vs. nonfrail 2.75%, P < 0.001). CONCLUSIONS: Frail home-dwelling patients undergoing elective vascular procedures are at high risk of not returning home after surgery. Preoperative frailty assessment appears to hold potential for counseling regarding postsurgery disposition and DC planning. PMID- 27263811 TI - Vascular Reconstruction Is Not Warranted in Most Civilian Traumatic Shank Vascular Injuries. AB - BACKGROUND: Operative management of traumatic shank vascular injuries (SVI) evolved significantly in the past few decades, thereby leading to a dramatic decrease in amputation rates. However, there is still controversy regarding the minimum number of patent shank arteries sufficient for limb salvage. METHODS: Between January 2006 and September 2011, 191 adult trauma patients presented to an urban level I trauma center in Miami, Florida, with traumatic lower extremity vascular injuries. Variables collected included age, gender, mechanism of injury, and clinical status at presentation. Surgical data included vessel injury, technical aspects of repair, associated complications, and outcomes. RESULTS: A total of 48 (25.1%) patients were identified comprising 66 traumatic shank arterial injuries. Mean age was 38.2 +/- 13.4 years, and the majority of patients were men (40 patients, 83.3%) presenting with blunt injuries (35 patients, 72.9%). Ligation was performed in 38 injured arteries (57.6%) and no vascular intervention was required in 20% of the patients. Vascular reconstruction was performed in only 6 patients (9.1%): 4 (6.1%) with concurrent popliteal trauma, 1 (1.5%) isolated anterior tibial, and 1 (1.5%) 3-vessel injury. Autogenous venous interposition conduit and polytetrafluoroethylene grafting were performed in 5 (7.6%) and 1 (1.5%) patient, respectively. All amputations (8 patients, 16.7%) occurred in blunt trauma patients presenting with unsalvageable limbs. The overall mortality rate in this series was 2.1%. CONCLUSIONS: Civilian shank arterial injuries are associated with acceptable rates of limb loss. Patients with a single-vessel patent inflow did not require vascular reconstruction in this series. Arterial reconstruction may no longer be determinant for successful management of isolated and double arterial SVI, whereas it is yet essential in the presence of 3-vessel or concurrent above-the-knee vascular injuries. Further investigation including larger number of patients is still warranted to define the role of conservative management in these complex injuries. PMID- 27263812 TI - Billowing of Endologix Powerlink Stent Graft in Post Endovascular Repair of Abdominal Aortic Aneurysm: Simultaneous Findings on CT and Ultrasound Imaging. AB - Endoleaks remain a main concern in endovascular aneurysm repair. A potential false positive in the diagnosis of endoleak surveillance includes "billowing," a phenomenon of the polytetrafluoroethylene plastic outer fabric of the stent graft is seen separated from the struts of the metallic endoskeleton. Contrast presents beyond the endoskeleton but is still contained within the graft. This is secondary to intermittent attachment of the graft to the endoskeleton, and is only found in the Endologix Powerlink. The finding of billowing has been previously reported and is a common knowledge by those who deploy the stent graft. We report a case where there is contemporaneous imaging on computed tomography angiography as well as on ultrasound. PMID- 27263813 TI - Postoperative Catheter-Directed Thrombolysis Versus Systemic Anticoagulation for Acute Superior Mesenteric Venous Thrombosis. AB - BACKGROUND: Little data evaluate catheter-directed thrombolysis (CDT) therapy as a sequential treatment of emergent surgery for patients with acute superior mesenteric venous thrombosis (ASMVT). We compared the outcomes of ASMVT patients receiving CDT via superior mesenteric artery (SMA) with those who had systemic anticoagulation after emergent laparotomy. METHODS: A single-center retrospective study of ASMVT patients receiving emergent laparotomy from May 2012 to April 2014 was performed. Patients in group I had postoperative systemic anticoagulation and patients in group II underwent postoperative CDT. The demography, etiology, imaging features, clinical outcomes, and complications were compared. Moreover, univariate analysis was performed to identify confounding variables of 30-day mortality. RESULTS: Thirty-two patients (20 males, mean age of 44.9 +/- 10.6 years) were included, 17 in group I and 15 in group II. No significant differences of demographic data, etiology, baseline value, and perioperative comorbidity were found. The rate of complete thrombus removal was significantly higher in group II than group I (29.4% vs. 80.0%, P = 0.001). The second-look laparotomy and repeat bowel resection (58.8% vs. 13.3%, P = 0.002) were required in fewer patients in group II (20.0% vs. 70.6%, P = 0.001). The incidence of short-bowel syndrome (SBS; 41.2% vs. 6.7%, P = 0.001) and 30-day mortality (41.2% vs. 6.7%, P = 0.001) were lower in group II. The 1-year survival was also better in group II (52.9% vs. 93.3%, P = 0.014). The incidence of massive abdominal hemorrhage requiring blood transfusion and surgical intervention was 11.8% in group I and 20.0% in group II (P = 0.645). The age, serum D-dimer level, SBS, and postoperative CDT were significant risk factors of 30-day mortality in this study. CONCLUSIONS: For ASMVT patients receiving emergent surgery and intraoperative thrombectomy, the algorithm with postoperative CDT via SMA is associated with more favorable clinical outcome compared with systemic anticoagulation. PMID- 27263814 TI - Popliteal Vein Puncture Technique Based on Bony Landmark Positioning in Catheter Directed Thrombolysis of Deep Venous Thrombosis: A Retrospective Review. AB - BACKGROUND: Catheter-directed thrombolysis (CDT) is an effective method for the treatment of deep venous thrombosis (DVT). The most widely used puncture technique involves the popliteal vein of the affected leg. We introduce a new puncture technique based on bony landmark positioning. METHODS: Between May 2012 and December 2014, we performed CDT in 96 cases of DVT using the puncture technique. The procedure is performed with the patient in the prone position on the angiography table. The popliteal vein is punctured according to tibial bony landmarks under fluoroscopic guidance. The needle puncture is made from the popliteal crease, along the direction of tibial lateral intercondylar eminence and parallel to the vertical axis. An introducer sheath is inserted after successful puncture followed by placement of a perfusion catheter of appropriate length in the thrombus. RESULTS: Technical success was achieved in 83 cases, with a success rate of 86.46% (83/96). The mean operation time was 38.6 +/- 16.8 min, the mean fluoroscopy time was 11.3 +/- 4.9 min, the mean effective dose (ED) was 77.2 +/- 25.4 mGy, the mean dose-area product (DAP) was 3,927.5 +/- 1,261 cGy cm(2). Compared with catheterization via incised ipsilateral small saphenous and contralateral femoral veins, the technique significantly shortened the operation and the X-ray exposure and reduced the dosage of ED and DAP. CONCLUSIONS: Popliteal vein puncture technique based on bony landmark positioning is a user friendly alternative to CDT, especially in the absence of ultrasound localization. PMID- 27263815 TI - Elevated Peak Systolic Velocity and Velocity Ratio from Duplex Ultrasound are Associated with Hemodynamically Significant Lesions in Arteriovenous Access. AB - BACKGROUND: Duplex ultrasound (DUS) is reliably used to detect lesions in the peripheral and carotid arterial beds and venous system. Although commonly used in clinical practice, duplex criteria to define lesions in arteriovenous access are not well characterized. This study will define the optimal Doppler-derived peak systolic velocity (PSV) and velocity ratio (VR) to identify >50% lesions in arteriovenous fistulas (AVF) and arteriovenous grafts (AVG). METHODS: This retrospective analysis includes patients with both DUS and fistulogram within 30 days. DUS-derived PSV and VR were recorded for 3 segments of each access and compared with fistulograms of the same 3 segments of each AV access. Receiver operating characteristic (ROC) was used to determine the optimal DUS criteria for diagnosis of >50% stenosis. RESULTS: Fifty pairs of imaging in 40 patients were available for analysis. Mean PSV and VR for segments with greater than 50% stenosis were significantly greater than those without; mean PSV of 480 cm/sec vs. 297 cm/sec (P < 0.001) and mean VR of 3.81 vs. 2.09 (P < 0.001). The ROC analysis demonstrated an optimal PSV of 404 and VR of 2.2 to diagnose >50% stenosis with area under the curve of 0.825 and 0.821 for PSV and VR, respectively. PSV of 500 had sensitivity (Se) of 0.60, specificity (Sp) of 0.86, positive predictive value (PPV) of 0.72, and negative predictive value (NPV) of 0.78. VR of 3.0 had Se of 0.52, Sp of 0.91, PPV of 0.77, and NPV of 0.75. CONCLUSIONS: DUS-derived PSV of 400 cm/sec and VR of 2.25 have good discrimination to predict greater than 50% stenosis in AVFs and AVGs. Given the broad range of velocities in AV accesses, a threshold of PSV greater than 500 cm/sec and VR greater than 3.0, will reliably identify graft-threatening lesions. Se and Sp of PSV 500 are 0.596 and 0.854, respectively. Se and Sp for VR 3.0 are 0.519 and 0.894, respectively. PMID- 27263816 TI - Clinical Value of Intraoperative Transit-Time Flow Measurement for Autogenous Radiocephalic Arteriovenous Fistula in Patients with Chronic Kidney Disease. AB - BACKGROUND: The intraoperative assessment of autogenous arteriovenous fistulas (AVF) is crucial for achieving an optimal surgical outcome; however, it is not easy to predict the adequacy of surgically created AVF. We used the transit-time flow measurement (TTFM) method to assess the anastomotic quality of AVF and to identify the cutoff value for predicting prognosis of established AVF. METHODS: Retrospective study, a total of 187 patients were included in this study. History of diabetes mellitus, hypertension, preoperative vein size, blood pressure, and other demographic data were collected. Surgery for creating radiocephalic AVF was performed by one surgeon, and intraoperative TTFM was performed. Flow parameters were recorded, including the maximal, mean, and minimal flow, and the pulsatility index (PI). Only mean flow <=70 mL/min regarded as failure. We reviewed patients' follow-up, and we defined "successful AVF" when the patients who managed hemodialysis using established AVF without clinical problems during follow-up. RESULTS: All patients had a successful operation with adequate mean flow. The established mean flow from the radial artery to the cephalic vein was 199.8 +/- 92.7 mL/min, and the PI was 0.57 +/- 0.16. None of the patients had any complication during the immediate postoperative period, including infection. Mean follow-up period were 72.4 +/- 42.7 weeks. Hemodialysis was maintained in 77.5% of the patients by using the established AVF, and the time to first hemodialysis with the established AVF after surgery was 61.0 +/- 22.7 days. Correlation analysis revealed that the time to first hemodialysis was related with mean flow (P = 0.049) and PI (P = 0.009) and successful AVF was related only with PI (P = 0.028). According to curve fit and regression analysis, PI for 95% limit of successful AVF was from 0.43 to 0.77. CONCLUSIONS: Intraoperative TTFM is valuable for the assessment of the quality of established AVFs. Especially PI was correlated successful hemodialysis management for over 12 months, the recommended acceptable range was 0.43-0.77. PMID- 27263817 TI - Thoracic Aorta Dimension Changes During Systole and Diastole: Evaluation with ECG Gated Computed Tomography. AB - BACKGROUND: This study was conducted to characterize the differences in the dimensions between systole and diastole in thoracic aorta in Chinese population with electrocardiogram (ECG)-gated multidetector computed tomography angiography (CTA) scans. METHODS: The CTAs of 56 patients (mean age 58.2 +/- 17.9 years; 42 men, 14 women) both in systole and diastole were obtained on a 64-slice ECG-gated multidetector CT scanner. Four anatomic levels of the thoracic aorta were selected for analysis (Level A: 1 cm proximal to the innominate artery; Level B: 1 cm distal to the left common carotid artery; Level C: 1 cm distal to the left subclavian artery; and Level D: 10 cm distal to the left subclavian artery). On each level, the maximal and the minimal diameters were measured both in systole and diastole. RESULTS: The paired sample t-test results showed a significant difference between the systolic and diastolic diameters in all individual subjects on every level. The diameter differences range between -1.7 mm (diastolic dimension is greater than systolic dimension) and 3.6 mm (systolic dimension is greater than diastolic dimension). The aortic diameters in diastolic phase are greater than in systolic phase in 18-22% subjects on different levels. A mean maximum diameter change of 2.68% (range -3.45% to 8.25%) and a mean minimum diameter change of 2.71% (range -5.05% to 8.38%) were found at Level A; a maximum diameter change of 2.89% (range -4.5% to 13.3%) and a minimum diameter change of 2.37% (range -5.2% to 14.9%) were found at Level B; a maximum diameter change of 2.81% (range -6.02% to 10.85%) and a minimum diameter change of 2.92% (range -7.14% to 9.62%) were found at Level C; and a maximum diameter change of 3.08% (range -1.76% to 10.36%) and a minimum diameter change of 2.93% (range 2.37% to 11.9%) were found at Level D. CONCLUSIONS: Our study verifies that the dimensional differences in thoracic aorta between systolic and diastolic phase are significant. But the pulsatility of thoracic aorta in Chinese population might be different from published literature. PMID- 27263818 TI - Clinical Effectiveness of Endovascular Therapy for Total Occlusion of the Subclavian Arteries: A Study of 67 Patients. AB - BACKGROUND: Endovascular therapy is a feasible option for total occlusion of the subclavian artery. The purpose of this study was to evaluate the effectiveness of stenting therapy by comparing it with that of surgical treatment in patients with total subclavian artery occlusion. METHODS: Between May 2007 and October 2013, 52 stents were placed in 67 patients who underwent endovascular therapy for the treatment of total atherosclerosis subclavian artery occlusion. During the same period, 21 patients underwent bypass surgery. All patients were followed at 3, 6, and 12 months after treatment and annually thereafter. RESULTS: Technical success was achieved in 77.6% patients in the endovascular group, while clinical success was achieved in 74.6%. Technical failure was noted in 15 patients, while the symptoms failed to resolve in 2. The rate of primary patency was 98.2% at 12 months, 94.3% at 24 months, and 92.1% at 3 years. Significant recurrent obstruction developed in 5 patients. No complications were observed in 5 patients with right side occlusion in whom embolic protection filters were used. Meanwhile, the technical success rate was 100% in the surgery group. One patient developed a major ischemic stroke during surgery (4.8%). The rate of primary patency was 100% at 12 months, 96.3% at 24 months, and 93.1% at 3 years. CONCLUSIONS: When performed by skilled surgeons, percutaneous revascularization with primary stenting is a safe and effective therapy for symptomatic total occlusion of the proximal subclavian artery. However, we recommend the use of embolic protection devices during the treatment of right side occlusions. Otherwise, surgery may be the best choice. PMID- 27263819 TI - An Uncommon Case of Type III Endoleak Treated with a Custom-made Thoracic Stent Graft. AB - Endovascular aortic repair (EVAR) has been shown to be a valid and minimally invasive alternative to open abdominal aortic aneurysm repair. A major shortcoming for EVAR is the need to submit patients to regular follow-up to detect potential complications such as endoleak, limb occlusion, aneurysm expansion, aneurysm rupture, infection, structural failure, and migration. In this case report, we describe an uncommon case of late type III endoleak due to complete detachment of the stent-graft main body segment from its suprarenal uncovered fixation stent. It was treated with a custom-made Relay((r)) NBS Plus (Bolton Medical, Barcelona, Spain) thoracic stent graft which also provided extra suprarenal fixation of the thoracic stent graft in the proximal neck. The postoperative period was uneventful and a computed tomography scan 1 year later revealed proper positioning of the stent graft and no signs of endoleak. The successful strategy chosen to correct this complication was at the same time original and infrequent, and also avoided potential complications related to open surgical repair and general anesthesia. PMID- 27263820 TI - Nonoperative Management of Traumatic Aortic Pseudoaneurysms. AB - BACKGROUND: Current blunt thoracic aortic injury (BTAI) guidelines recommend early repair of traumatic pseudoaneurysms (PSAs) due to risk for subsequent aortic rupture. Recent analyses indicate that early repair is required only in the setting of high-risk features, while delayed repair is safe and associated with lower morbidity and mortality in appropriately selected patients. To evaluate the appropriate indications for nonoperative management (NOM) of traumatic PSAs, we performed a systematic review of studies reporting outcomes for this management strategy. We hypothesized that NOM is safe in appropriately selected patients with traumatic aortic PSAs. METHODS: English language single- and multi-institutional series reporting NOM of traumatic thoracic aortic PSAs were identified by systematic literature search and review. A descriptive analysis was performed of NOM, with stratification by lesion size and patient follow-up. The primary outcomes were late aortic intervention, aortic-related death, and all-cause mortality. RESULTS: Eighteen studies, which included 937 patients with traumatic PSAs, were analyzed. One hundred ninety-one patients were managed nonoperatively. The primary indication for NOM was prohibitive risk for aortic repair due to severe comorbidities or concurrent injuries. Where reported, PSAs with <50% circumferential involvement accounted for 88% of lesions selected for NOM. Late interventions were required in 4% of patients. Inpatient aortic related mortality was 2%, and all-cause inpatient mortality was 32%. Although survival at up to 4-7 years was reported, postdischarge follow-up after PSA NOM was limited to <1 year in most studies. CONCLUSIONS: NOM of traumatic aortic PSAs is a common practice in BTAI series reporting lesion-specific management, and is associated with low rates of treatment failure. These findings suggest that routine early repair may not be required for traumatic PSAs, particularly for lesions limited to <50% of the aortic circumference. Definitive repair can be delayed until patient stability and repair timing can be guided by assessment of lesion stability on follow-up imaging. PMID- 27263821 TI - Upper Extremity Steal Syndrome Is Associated with Atherosclerotic Burden and Access Configuration. AB - BACKGROUND: Clinically significant steal syndrome occurs in a subset of dialysis patients with arteriovenous (AV) access. Factors associated with steal are poorly understood. Severe symptoms require access revision or sacrifice, potentially jeopardizing access options. Our objective was to review our dialysis access experience to identify factors associated with significant steal syndrome. METHODS: We reviewed all adult patients undergoing their first permanent upper extremity access, AV fistula (AVF) or AV graft (AVG), between January 2008 and July 2011 at a single center. Medical, demographic, and access characteristics were collected from our electronic medical record and a local dialysis center's database. Patients who required correction of steal syndrome were compared with the larger access cohort. Statistical analysis included Fisher's exact test and chi(2) for noncontinuous variables and unpaired t-test for continuous variables. RESULTS: Of the 303 patients, 15 required correction for steal syndrome (8 of 232 AVF and 7 of 71 AVG). Eight were ligated; 2 were initially banded, then ligated; and 5 underwent distal revascularization with interval ligation. Coronary artery disease was more prevalent in steal syndrome patients (66.7% vs. 25%, P = 0.001); the same was found with peripheral arterial disease (40% vs. 13.8%, P = 0.02). Furthermore, more patients with steal syndrome were on clopidogrel for cardiovascular reasons (40% vs. 9%, P = 0.002). Steal syndrome only developed with AVF and AVG using brachial artery inflow. No cases of steal syndrome arose from radial/ulnar inflow (P = 0.03). All AVG with steal syndrome had a straight configuration; no looped AVG developed steal (P = 0.02). Other patient characteristics such as age, sex, race, hypertension, diabetes mellitus, congestive heart failure, cerebrovascular accident, cause of end-stage renal disease, and other medication history were not different between groups. CONCLUSIONS: Clinically significant steal syndrome is associated with disease in coronary and peripheral arterial beds. In addition, the use of brachial artery inflow and straight AVG configuration is associated with steal syndrome. Consideration should be given to construction of access using smaller forearm arteries and looped AVG configuration in patients with high risk for steal. In addition, such patients may require more vigilant monitoring for development of steal after access construction. PMID- 27263822 TI - Bilateral Common Iliac Artery Endofibrosis in a Recreational Cyclist: Case Report and Review of the Literature. AB - External iliac artery endofibrosis is a rare medical condition typically encountered in young endurance athletes, mainly cyclists. Iliac endofibrosis usually develops in the external iliac artery and is rarely seen in the common iliac or in common femoral arteries. We describe a unique case of a patient who was not a professional or high-endurance cyclist. The lesions in our case appeared to be bilateral in the common iliac arteries and were not limited to the external iliac artery as most commonly described. We present an overview of the literature regarding this medical condition. PMID- 27263823 TI - Can a Neutrophil-Lymphocyte Ratio Derived from Preoperative Blood Tests Predict Arteriovenous Fistula Maturation? AB - BACKGROUND: To evaluate the association between inflammatory markers expressed as neutrophil-lymphocyte ratio (NLR) and process of arteriovenous fistula (AVF) maturation. METHODS: A retrospective review of patients with end-stage renal disease referred for formation of a new AVF in one center. Patients referred to the vascular service in the University Hospital of Limerick for creation of vascular access between 2009 and 2013. The association between NLR, calculated from preoperative blood tests, and functional fistula maturation, as determined by successful use of the AVF for 6 consecutive hemodialysis sessions, was investigated using univariate and logistic regression analyses. A logistic regression analysis was carried out to assess potential influence from other factors related to AVF maturation. Stepwise regression test was performed including the NLR. RESULTS: Overall AVF functional maturation rate in our study was 53.7% (66/123). Patients with matured AVFs had an NLR of 4.850 (1.8-15.7) compared with 3.554 (1.7-15.0); this difference was found to be significant (P = 0.024). Female gender (P = 0.008) and a history of kidney transplant (P = 0.004) were the only independent factors of fistula maturation outcome in a logistic regression model. CONCLUSION: Increased level of NLR was found to be associated with fistula maturation; however, more studies are needed to validate this finding. PMID- 27263824 TI - NUT midline carcinoma of the lung, a rare form of lung cancer. PMID- 27263826 TI - Cannabinoid 2 (CB2) receptor agonism reduces lithium chloride-induced vomiting in Suncus murinus and nausea-induced conditioned gaping in rats. AB - We aimed to investigate the potential anti-emetic and anti-nausea properties of targeting the cannabinoid 2 (CB2) receptor. We investigated the effect of the selective CB2 agonist, HU-308, on lithium chloride- (LiCl) induced vomiting in Suncus murinus (S. murinus) and conditioned gaping (nausea-induced behaviour) in rats. Additionally, we determined whether these effects could be prevented by pretreatment with AM630 (a selective CB2 receptor antagonist/inverse agonist). In S. murinus, HU-308 (2.5, 5mg/kg, i.p.) reduced, but did not completely block, LiCl-induced vomiting; an effect that was prevented with AM630. In rats, HU-308 (5mg/kg, i.p.) suppressed, but did not completely block, LiCl-induced conditioned gaping to a flavour; an effect that was prevented by AM630. These findings are the first to demonstrate the ability of a selective CB2 receptor agonist to reduce nausea in animal models, indicating that targeting the CB2 receptor may be an effective strategy, devoid of psychoactive effects, for managing toxin-induced nausea and vomiting. PMID- 27263825 TI - Single-step electrical field strength screening to determine electroporation induced transmembrane transport parameters. AB - The design of effective electroporation protocols for molecular delivery applications requires the determination of transport parameters including diffusion coefficient, membrane resealing, and critical electric field strength for electroporation. The use of existing technologies to determine these parameters is time-consuming and labor-intensive, and often results in large inconsistencies in parameter estimation due to variations in the protocols and setups. In this work, we suggest using a set of concentric electrodes to screen a full range of electric field strengths in a single test to determine the electroporation-induced transmembrane transport parameters. Using Calcein as a fluorescent probe, we developed analytical methodology to determine the transport parameters based on the electroporation-induced pattern of fluorescence loss from cells. A monolayer of normal human dermal fibroblast (NHDF) cells were pre-loaded with Calcein and electroporated with an applied voltage of 750V with 10 and 50 square pulses with 50MUs duration. Using our analytical model, the critical electric field strength for electroporation was found for the 10 and 50 pulses experiments. An inverse correlation between the field strength and the molecular transport time decay constant, and a direct correlation between field strength and the membrane permeability were observed. The results of this work can simplify the development of electroporation-assisted technologies for research and therapies. PMID- 27263827 TI - Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals. AB - Lacosamide is an anti-epileptic drug that is also used for the treatment of painful diabetic neuropathy acting through voltage-gated sodium channels. The aim of this work was to evaluate the effects of acute application of lacosamide on the electrical activity of corneal cold nerve terminals in lacrimo-deficient guinea pigs. Four weeks after unilateral surgical removal of the main lachrimal gland in guinea pigs, corneas were excised and superfused in vitro at 34 degrees C for extracellular electrophysiological recording of nerve terminal impulse activity of cold thermosensitive nerve terminals. The characteristics of the spontaneous and the stimulus-evoked (cooling ramps from 34 degrees C to 15 degrees C) activity before and in presence of lacosamide 100uM and lidocaine 100uM were compared. Cold nerve terminals (n=34) recorded from dry eye corneas showed significantly enhanced spontaneous activity (8.0+/-1.1 vs. 5.2+/-0.7imp/s; P<0.05) and cold response (21.2+/-1.7 vs. 16.8+/-1.3imp/s; P<0.05) as well as reduced cold threshold (1.5+/-0.1 vs. 2.8+/-0.2 Delta degrees C; P<0.05) to cooling ramps compared to terminals (n=58) from control animals. Both lacosamide and lidocaine decreased spontaneous activity and peak response to cooling ramps significantly (P<0.05). Temperature threshold was increased by the addition of lidocaine (P<0.05) but not lacosamide (P>0.05) to the irrigation fluid. In summary, the application of lacosamide results in a significant decrease of the augmented spontaneous activity and responsiveness to cold of corneal sensory nerves from tear-deficient animals. Based on these promising results we speculate that lacosamide might be used to reduce the hyperexcitability of corneal cold receptors caused by prolonged ocular surface dryness due to hyposecretory or evaporative dry eye disease. PMID- 27263828 TI - Genomic Dark Matter Illuminated: Anopheles Y Chromosomes. AB - Hall et al. have strategically used long-read sequencing technology to characterize the structure and highly repetitive content of the Y chromosome in Anopheles malaria mosquitoes. Their work confirms that this important but elusive heterochromatic sex chromosome is evolving extremely rapidly and harbors a remarkably small number of genes. PMID- 27263830 TI - Construction of probe of the plant growth-promoting bacteria Bacillus subtilis useful for fluorescence in situ hybridization. AB - Strains of Bacillus subtilis are plant growth-promoting bacteria (PGPB) of many crops and are used as inoculants. PGPB colonization is an important trait for success of a PGPB on plants. A specific probe, based on the 16 s rRNA of Bacillus subtilis, was designed and evaluated to distinguishing, by fluorescence in situ hybridization (FISH), between this species and the closely related Bacillus amyloliquefaciens. The selected target for the probe was between nucleotides 465 and 483 of the gene, where three different nucleotides can be identified. The designed probe successfully hybridized with several strains of Bacillus subtilis, but failed to hybridize not only with B. amyloliquefaciens, but also with other strains such as Bacillus altitudinis, Bacillus cereus, Bacillus gibsonii, Bacillus megaterium, Bacillus pumilus; and with the external phylogenetic strains Azospirillum brasilense Cd, Micrococcus sp. and Paenibacillus sp. The results showed the specificity of this molecular probe for B. subtilis. PMID- 27263832 TI - 3D hierarchical MnO2 nanorod/welded Ag-nanowire-network composites for high performance supercapacitor electrodes. AB - 3D MnO2 nanorod/welded Ag-nanowire-network supercapacitor electrodes were prepared. Welding treatment of the Ag nanowire-network leads to low resistance and long lifetime. Galvanostatic charge/discharge (GCD) induces an ever-lasting morphology changing from flower-like to honeycomb-like for MnO2, which manifests as increasing specific capacitance to 663.4 F g(-1) after 7000 GCD cycles. PMID- 27263829 TI - Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses. AB - Dehydroepiandrosterone (DHEA) is a hormone that plays an important role in the modulation of inflammatory responses. However, the precise mechanisms that link the actions of this androgen with protection or susceptibility to inflammatory bowel diseases (IBD) remain uknown. Here we showed that low dose DHEA inhibited proliferation of spleen cells and IFN-u production. The hormone was not toxic to myeloid lineage cells, although it caused necrosis of spleen cells at the intermediate and highest doses in vitro (50 and 100MUM). The treatment of C57BL/6 mice with DHEA during colitis induction by dextran sodium sulfate (DSS) led to a reduction in weight loss and clinical signs of disease. There were decreased peripheral blood monocytes on day 6 of DSS exposure and treatment, besides increase in circulating neutrophils in the tissue repair phase. DHEA also led to reduced lamina propria cellularity and restoration of normal colon length. These results were accompanied by decreased expression of IL-6 and TGF-beta mRNA, while IL-13 was augmented in the colon on day 6, which was probably related to attenuation of inflammation. There was retention of CD4(+) cells in the spleen after use of DHEA, along with augmented frequency of CD4(+)IL-4(+) cells, decreased CD4(+)IFN-gamma(+) in spleen and constrained CD4(+)IL-17(+) population in the mesenteric lymph nodes. Moreover, splenocytes of mice treated with DHEA became hyporesponsive, as observed by reduced proliferation after re-stimulation ex-vivo. In conclusion, DHEA modifyies leukocyte activity and balances the exacerbated immune responses which drive local and systemic damages in IBD. PMID- 27263831 TI - Evaluation of the Punch-itTM NA-Sample kit for detecting microbial DNA in blood culture bottles using PCR-reverse blot hybridization assay. AB - DNA extraction efficiency affects the success of PCR-based method applications. The Punch-itTM NA-Sample kit for extracting DNA by using paper chromatography is technically easy to use and requires just two reagents and only 10min to complete. The Punch-itTM NA-Sample kit could be offered as a rapid, accurate, and convenient method for extracting bacterial and fungal DNA from blood culture bottles. We compared the efficiencies of the commercial kit (Punch-itTM NA-Sample kit) and an in-house conventional boiling method with Chelex-100 resin for DNA extraction from blood culture bottles. The efficiency of the two DNA extraction methods was assessed by PCR-reverse blot hybridization assay (PCR-REBA, REBA Sepsis-ID) for detecting Gram positive (GP) bacteria, Gram negative (GN) bacteria, and Candida species with 196 positive and 200 negative blood culture bottles. The detection limits of the two DNA extraction methods were 10(3)CFU/mL for GP bacteria, 10(3)CFU/mL for GN bacteria, and 10(4)CFU/mL for Candida. The sensitivity and specificity of the Punch-itTM NA-Sample kit by REBA Sepsis-ID were 95.4% (187/196) and 100% (200/200), respectively. The overall agreement of the two DNA extraction methods was 98.9% (392/396). Three of four samples showing discrepant results between the two extraction methods were more accurately matched up with the Punch-itTM NA-Sample kit based on conventional culture methods. The results indicated that the Punch-itTM NA-Sample kit extracted bacterial and fungal DNA in blood culture bottles and allowed extracted DNA to be used in molecular assay. PMID- 27263833 TI - Scaling of the fast-start escape response of juvenile bluegills. AB - Morphology, size and physiological properties change markedly across fish ontogeny. This impacts locomotor performance and organismal fitness, although the effects are unpredictable due to the complexity of phenotype-function relationships. Morphological and behavioral changes with growth are often paralleled by changes in habitat use, diet and vulnerability to predators. Our goal was to quantify the changes in external morphology and escape performance throughout post-larval development in bluegill sunfish (Lepomis macrochirus), and place these changes in context with known changes in habitat use in the field. Development into adult ecomorphs is associated with phenotypic plasticity in response to habitat-specific differences in diet. On this basis, we hypothesized that variation in morphology and performance would increase during bluegill ontogeny as diversification of adult ecomorphs occurred. However, we found that variation in phenotype and escape performance decreased during early ontogeny. Phenotypic variation expanded later in development, after fish gained access to the variety of habitats and food types that may favor phenotypic plasticity. Performance is predicted to decline with growth due to the differential scaling of inertia and cross-sectional area, a major determinant of muscle force. In contrast, acceleration increased with size, and velocity and acceleration increased more rapidly with size than predicted. Post-larval maturation in bluegill featured a shift to a deeper body shape, and an increase in the relative size of the anal and caudal fins. This was a likely factor in the deviation of escape performance scaling relationships from predictions based on geometric similarity. PMID- 27263835 TI - Amplitude of low frequency fluctuations during resting state predicts social well being. AB - Social well-being represents primarily public phenomena, which is crucial for mental and physical health. However, little is known about the neural basis of this construct, especially how it is maintained during resting state. To explore the neural correlates of social well-being, this study correlated the regional fractional amplitude of low frequency fluctuations (fALFF) with social well-being of healthy individuals. The results revealed that the fALFF in the bilateral posterior superior temporal gyrus (pSTG), right anterior cingulate cortex (ACC), right thalamus and right insula positively predicted individual differences in social well-being. Furthermore, we demonstrated the different role of three pursuits of human well-being (i.e., pleasure, meaning and engagement) in these associations. Specifically, the pursuits of meaning and engagement, not pleasure mediated the effect of the fALFF in right pSTG on social well-being, whereas the pursuit of engagement mediated the effect of the fALFF in right thalamus on social well-being. Taken together, we provide the first evidence that spontaneous brain activity in multiple regions related to self-regulatory and social cognitive processes contributes to social well-being, suggesting that the spontaneous activity of the human brain reflects the efficiency of social well being. PMID- 27263834 TI - Safety pharmacology investigations on the nervous system: An industry survey. AB - The Safety Pharmacology Society (SPS) conducted an industry survey in 2015 to identify industry practices as they relate to central, peripheral and autonomic nervous system ('CNS') drug safety testing. One hundred fifty-eight (158) participants from Asia (16%), Europe (20%) and North America (56%) responded to the survey. 52% of participants were from pharmaceutical companies (>1000 employees). Oncology (67%) and neurology/psychiatry (66%) were the most frequent target indications pursued by companies followed by inflammation (48%), cardiovascular (43%), metabolic (39%), infectious (37%), orphan (32%) and respiratory (29%) diseases. Seizures (67% of participants), gait abnormalities (67%), tremors (65%), emesis (56%), sedation (52%) and salivation (47%) were the most commonly encountered CNS issues in pre-clinical drug development while headache (65%), emesis/nausea (60%), fatigue (51%) and dizziness (49%) were the most frequent issues encountered in Phase I clinical trials. 54% of respondents reported that a standard battery of tests applied to screen drug candidates was the approach most commonly used to address non-clinical CNS safety testing. A minority (14% of all participants) reported using electroencephalography (EEG) screening prior to animal inclusion on toxicology studies. The most frequent group size was n=8 for functional observation battery (FOB), polysomnography and seizure liability studies. FOB evaluations were conducted in a dedicated room (78%) by blinded personnel (66%) with control for circadian cycle (55%) effects (e.g., dosing at a standardized time; balancing time of day across treatment groups). The rat was reported as the most common species used for seizure liability, nerve conduction and drug-abuse liability testing. PMID- 27263837 TI - About Congenital Afibrinogenemia. PMID- 27263836 TI - Images in Haematology. PMID- 27263838 TI - Differential associations of Borrelia species with European badgers (Meles meles) and raccoon dogs (Nyctereutes procyonoides) in western Poland. AB - European badgers and raccoon dogs and their associated ticks and lice were assayed for the presence of Lyme borreliosis and relapsing fever-group spirochete DNA in western Poland. Analyses of blood, ear-biopsy and liver samples revealed that 25% of 28 raccoon dogs and 12% of 34 badgers were PCR positive for borreliae. Borrelia garinii was the dominant species in raccoon dogs (62.5%), followed by B. afzelii (25%) and B. valaisiana (12.5%). PCR-positive badgers were infected only with B. afzelii. A total of 351 attached ticks was recovered from 23 (82%) of the raccoon dogs and 13 (38%) of the badgers. Using a nested PCR targeting the ITS2 fragments of Ixodes DNA, four Ixodes species were identified: I. ricinus, I. canisuga, I. hexagonus, and one provisionally named I. cf. kaiseri. Ixodes canisuga and I. ricinus prevailed on both host species. The highest infection prevalence was detected in I. ricinus, followed by I. canisuga and I. cf. kaiseri. Borrelia garinii and B. afzelii accounted for 61.6% and 30.1% of the infections detected in all PCR-positive ticks, respectively. Four other Borrelia species (B. burgdorferi sensu stricto, B. valaisiana, B. lusitaniae and B. miyamotoi) were detected only in I. ricinus from raccoon dogs. Moreover, Borrelia DNA, mostly B. garinii, was detected in 57 (81.4%) of 70 Trichodectes melis lice derived from 12 badgers. The detection of B. afzelii in one-half of PCR-positive biopsies reconfirms previous associations of this species with mammalian hosts, whereas the high prevalence of B. garinii in feeding lice and I. ricinus ticks (including larvae) demonstrates that both carnivores serve as hosts for B. garinii. The lack of B. garinii DNA in the tissues of badgers versus its prevalence in raccoon-dog biopsies, however, incriminates only the latter carnivore as a potential reservoir host. PMID- 27263840 TI - Anti-D and intravenous immunoglobulin treatments in chronic idiopathic thrombocytopenic purpura. PMID- 27263839 TI - Interactions of complex polymers with nanoporous substrate. AB - With the advance of polymer synthesis, polymers that possess unique architectures such as stars or cyclic chains, and unique chemical composition distributions such as block copolymers or statistical copolymers have become frequently encountered. Characterization of these complex polymer systems drives the development of interactive chromatography where the adsorption of polymers on the porous substrate in chromatography columns is finely tuned. Liquid Chromatography at the Critical Condition (LCCC) in particular makes use of the existence of the Critical Adsorption Point (CAP) of polymers on solid surfaces and has been successfully applied to characterization of complex polymer systems. Interpretation and understanding of chromatography behaviour of complex polymers in interactive chromatography motivates theoretical/computational studies on the CAP of polymers and partitioning of these complex polymers near the CAP. This review article covers the theoretical questions encountered in chromatographic studies of complex polymers. PMID- 27263841 TI - Renal involvement in multiple myeloma: new insight into mechanisms. PMID- 27263842 TI - Ferritin and haematological values in healthy elderly Nigerians. AB - Two-hundred Nigerians (65 years and above) were studied and compared with control (18-50 years). Haematocrit, haemoglobin, mean corpuscular haemoglobin concentration, mean corpuscular haemoglobin, mean corpuscular volume, platelets and ferritin were analyzed. Mean ferritin levels were 105 +/- 30 MUg/L and 72 +/- 10 MUg/L (males and females respectively). Mean MCV, MCH and MCHC were 94.6 +/- 9.0 fl, 93.6 +/- 9.0 fl, 31.5 +/- 3.0 pg, 31.4 +/- 4.4 pg, 348 +/- 30 g/L, and 347 +/- 42 g/L. Mean haematocrits were 37 +/- 4%, 36 +/- 4%, while mean haemoglobins levels were 132 +/- 24 g/L and 129 +/- 1 g/L. RBC counts were 4.1 +/ 0.8 x 1012/L, and 4.0 +/- 0.5 x 1012/L. Mean total WBC counts were 6.4 +/- 1.5 x 109/L and 6.3 +/- 0.7 x 109/L; mean platelets were 170 +/- 60 x 109/L, 184 +/- 5 x 109/L. All haematological parameters were similar in both aged males and females, except ferritin, haematocrit, RBC and haemoglobin, which were significantly higher in males (p< 0.05). Significant sex differences exist in all the parameters, of control except MCV and total WBC count. There were significant differences in all the haematological parameters between the controls and the aged (p< 0.05), and between the aged (65-84 years) and the very aged (85-105 years) (p< 0.05). Reference haematological range needs to be established for the elderly Nigerians. PMID- 27263843 TI - Homocysteine levels in Turkish children. AB - Hyperhomocysteinemia is a known risk factor for cerebrovascular, peripheral vascular, coronary heart disease, and thrombosis. Several data related to total homocysteine concentrations for children and adolescents were reported from different populations. But no data are available comparing homocysteine levels analyzing according to age ranges in Turkish children. So, we aimed to achieve a reference range for total homocysteine in Turkish children. Plasma total homocysteine concentrations were measured in 177 healthy children within three groups according to age range (1-6, 7-11, 12-17 y). Mean tHcy concentrations were determined (7.77 +/- 4.13 MUmol/L). Homocysteine were lowest in younger children and increased with age: 1-6 y (3.87 +/- 1.44 MUmol/L), 7-11 y (8.70 +/- 1.40 MUmol/L), and 12-17 y (13.54 +/- 1.49 MUmol/L). We observed no significant differences in tHcy values between girls and boys in all groups. We suggest that total homocysteine levels must be evaluated in children according to age. PMID- 27263844 TI - Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish deep vein thromboembolic patients with and without prothrombin 20210 G-A. AB - Prothrombin 20210 G-A mutation is a common factor that predispose to thrombosis. The effect of the mutations in PAI-1 gene on the risk of thrombosis is controversial. We aimed to evaluate the role of these two polymorphisms in Turkish patients with deep vein thrombosis. Although there was no statistically significant difference in patient and control group for the distribution of PAI-1 4G/5G polymorphism in the present study, the risk of thrombosis increased from 3.4 fold to 8.4 in patients carrying PT20210 A and PAI-1 4G. PMID- 27263845 TI - Quantification of the FLI1 and CXCR4 gene expressions in acute lymphoblastic leukemia (ALL) patients with t(12,21). AB - The presence of the t(12,21) is associated with good response to therapy in acute lymphoblastic leukemia (ALL) but molecular background of this pathology is not clear. FLI1 gene plays important roles in normal regulation of myeloid hematopoiesis and leukemogenesis. The chemokine receptor CXCR4 gene may play a role in the homing of hematopoietic stem cells. Our aim was to investigate possible relationships between t(12,21) existence and expression changes of these two genes (FLI1, CXCR4) in ALL. Thirty-one ALL patients were investigated. Twenty one of these patients were t(12,21) carriers. We used the Quantitative Real-Time RT-PCR. Obtained results were compared to normal bone marrow samples of five healthy subjects. Expression differences were not found significant in both groups. Our study was the first attempt to quantify these genes in t(12,21) patients. We conclude that Quantitative RT-PCR is a reliable method for the monitoring of these gene expressions and similar studies should expand to other translocations in haematology. PMID- 27263846 TI - Splenomegaly due to the use of granulocyte-colony stimulating factor. AB - Granulocyte-colony stimulating factor (G-CSF) is a growth factor used for stem cell mobilization and neutropenia treatment. We report that splenomegaly was detected in a 16-years-old patient with acute lymphoblastic leukemia following the administration of G-CSF. The presence of splenomegaly in the patients receiving G-CSF may be related to the use of G-CSF. PMID- 27263847 TI - Bone marrow necrosis in a patient with non-Hodgkin lymphoma. AB - Bone marrow necrosis is a rare but ominous finding in various malignant and nonmalignant disorders. It is usually a postmortem diagnosis, but with the advent of modern imaging methods and clinical suspicion, bone marrow necrosis can be diagnosed as antemortem, especially in malignant disorders. We report a 60-years old man with newly diagnosed non-Hodgkin lymphoma presenting with anemia and very high level of alkaline phosphatase. On bone marrow biopsy, it was noted with extensive BMN characterized by cellular debris with indistinct cellular margin and abnormally eosinophilic staining cytoplasm. Despite the prompt institution of aggressive chemotherapy, one week later, liver function tests gradually deteriorated and the patient succumbed. Given the high mortality rate, when the bone marrow necrosis is suspected especially in a patient with malignancy, disease specific treatment and vigorous supportive measures should be immediately commenced. PMID- 27263848 TI - Ocular lymphoma in two cases. AB - We are reporting primary ocular lymphoma in two male patients who are sixty seven and seventy years old. The first case was admitted to the hospital after an ophthalmologic examination that revealed a soft, pink homogenous vascular mass originating from the conjunctiva, and extending behind the bulbous oculi, completely covering the upper quadrant of the right eye. There was also right axial exophthalmy. Ocular adnexal and intraocular involvement was seen at physical examination and orbital imaging. Optic atrophy and retinal pigment epitheloid changes were seen at fundoscopic examination. Biopsy taken from the right eye revealed mucosa associated lymphoid tissue (MALT) lymphoma. The case was diagnosed as primary ocular adnexal and intraocular lymphoma. Left eye was normal. The cranial, thoracic and abdominal imaging examinations and other laboratory analysis were normal. He received six courses of CNOP (cyclophosphamide, mitoxantrone, vincristine, prednisolone) chemotherapy and full remission was achieved following radiotherapy. He is in full remission for two years. The second case came with proptosis and chemosis at the lower part of left eye. The cornea and anterior chamber were normal. At fundoscopy, there was superficial haemorrhage on temporal edge of discus, wide haemorrhage at the periphery of discus at the same level with parafoveal little haemorrhage focus. Orbital imaging revealed a retroorbital mass. A biopsy was done from the retroorbital mass by craniotomy. B-cell small lymphocytic lymphoma was diagnosed. Right eye was normal. He received radiotherapy.after a diagnosis of ocular adnexal lymphoma. PMID- 27263849 TI - Silicone gel sheet dressing for sclerodermatous type chronic graftversus- host disease (cGVHD). AB - Systemic sclerosis is an autoimmune disease characterized by endothelial cell injury, fibroblast activation and immunological aberrations. Generalized form of the disease involves skin and other organs. Progressive sclerodermatous type cGVHD is the difficult type to treat. Immunosuppressors are the most commonly used treatment regimens. Topical silicone gel sheet (SGS) were first used in the treatment of burn wound and following their initial successes have begun to be used in the treatment of hypertrophic scars and keloids. To best of our knowledge, this is the first patient with extensive sclerodermatous type cGVHD in whom SGS was applied on to the skin of the antecubital region. After a six months application of SGS, the skin of this region was remarkably soft and thick compared to other regions of the arm. The result indicate that SGS may be an useful tool for the treatment of extensive sclerodermatous type cGVHD. PMID- 27263850 TI - Images in Hematology. PMID- 27263851 TI - A case with chronic eosinophilic leukemia resulting in blastic transformation. PMID- 27263853 TI - Unravelling the structural plasticity of stretched DNA under torsional constraint. AB - Regions of the genome are often held under torsional constraint. Nevertheless, the influence of such constraint on DNA-protein interactions during genome metabolism is still poorly understood. Here using a combined optical tweezers and fluorescence microscope, we quantify and explain how torsional constraint influences the structural stability of DNA under applied tension. We provide direct evidence that concomitant basepair melting and helical unwinding can occur in torsionally constrained DNA at forces >~50 pN. This striking result indicates that local changes in linking number can be absorbed by the rest of the DNA duplex. We also present compelling new evidence that an overwound DNA structure (likely P-DNA) is created (alongside underwound structures) at forces >~110 pN. These findings substantiate previous theoretical predictions and highlight a remarkable structural plasticity of torsionally constrained DNA. Such plasticity may be required in vivo to absorb local changes in linking number in DNA held under torsional constraint. PMID- 27263852 TI - A novel biomarker panel for irritable bowel syndrome and the application in the general population. AB - Biological markers that measure gut health and diagnose functional gastro intestinal (GI) disorders, such as irritable bowel syndrome (IBS), are lacking. The objective was to identify and validate a biomarker panel associated with the pathophysiology of IBS that discriminates IBS from healthy controls (HC), and correlates with GI symptom severity. In a case-control design, various plasma and fecal markers were measured in a cohort of 196 clinical IBS patients and 160 HC without GI symptoms. A combination of biomarkers, which best discriminates between IBS and HC was identified and validated in an independent internal validation set and by permutation testing. The correlation between the biomarker panel and GI symptom severity was tested in IBS patients and in a general population cohort of 958 subjects. A set of 8 biomarker panel was identified to discriminate IBS from HC with high sensitivity (88.1%) and specificity (86.5%). The results for the IBS subtypes were comparable. Moreover, a moderate correlation was found between the biomarker panel and GI symptom scores in the IBS (r = 0.59, p < 0.001) and the general population cohorts (r = 0.51, p = 0.003). A novel multi-domain biomarker panel has been identified and validated, which correlated moderately to GI symptom severity in IBS and general population subjects. PMID- 27263854 TI - Overall safety and efficacy of high-dose and low-dose intravenous glucocorticoid therapy in patients with moderate-to-severe active Graves' ophthalmopathy. AB - The objective of this study was to compare the safety and efficacy of high-dose and low-dose intravenous (iv) glucocorticoid (GC) therapy in patients with Graves' ophthalmopathy (GO) and to investigate which factors may help determine appropriate iv GC doses. The medical records of 43 patients who received different doses of iv GCs for GO were retrospectively reviewed. Twenty patients received high-dose iv GCs (HD group, cumulative dose 9.0-12.0 g) and 18 received low-dose iv GCs (LD group, cumulative dose 4.5 g). Five patients with previous treatment for GO were excluded. Changes in ophthalmic parameters after treatment and frequencies of adverse effects due to GCs of the 2 groups were compared. We also reviewed the incidence of GO progression and hepatic dysfunction after patients were discharged. We evaluated correlations among pretreatment (before treatment) ophthalmic parameters and investigated useful predictive factors for determining iv GC doses. There were no significant differences in ophthalmic parameters reflecting treatment efficacy or overall safety between the groups. Among baseline ophthalmic parameters, corrected signal intensity ratio (cSIR) correlated well with magnetic resonance imaging findings and were more strongly associated with changes in ophthalmic parameters after treatment in the HD group than in the LD group, indicating that pretreatment cSIR might be useful for determining iv GC doses. In conclusion, there were no significant differences in overall safety and efficacy between high-dose and low-dose iv GC therapy in patients with active GO. Further randomized clinical trials with longer observation periods are required to establish the optimal treatment regimen of GO. PMID- 27263855 TI - Iron(ii)-triazole core-shell nanocomposites: toward multistep spin crossover materials. AB - The first SCO@SCO core-shell nanomaterials have been synthesized by the step-by step microemulsion method. The observed gyroscopic core-shell nanocomposites exhibit three-step spin crossover behaviour with thermal hysteresis at around room temperature. This offers an efficient and novel strategy for the development of multistable SCO materials. PMID- 27263856 TI - Free-Standing Undoped ZnO Microtubes with Rich and Stable Shallow Acceptors. AB - Fabrication of reliable large-sized p-ZnO is a major challenge to realise ZnO based electronic device applications. Here we report a novel technique to grow high-quality free-standing undoped acceptor-rich ZnO (A-ZnO) microtubes with dimensions of ~100 MUm (in diameter) * 5 mm (in length) by optical vapour supersaturated precipitation. The A-ZnO exhibits long lifetimes (>1 year) against compensation/lattice-relaxation and the stable shallow acceptors with binding energy of ~127 meV are confirmed from Zn vacancies. The A-ZnO provides a possibility for a mimetic p-n homojunction diode with n(+)-ZnO:Sn. The high concentrations of holes in A-ZnO and electrons in n(+)-ZnO make the dual diffusion possible to form a depletion layer. The diode threshold voltage, turn on voltage, reverse saturated current and reverse breakdown voltage are 0.72 V, 1.90 V, <10 MUA and >15 V, respectively. The A-ZnO also demonstrates quenching free donor-acceptor-pairs (DAP) emission located in 390-414 nm with temperature of 270-470 K. Combining the temperature-dependent DAP violet emission with native green emission, the visible luminescence of A-ZnO microtube can be modulated in a wide region of colour space across white light. The present work opens up new opportunities to achieve ZnO with rich and stable acceptors instead of p-ZnO for a variety of potential applications. PMID- 27263857 TI - MCRS1 associates with cytoplasmic dynein and mediates pericentrosomal material recruitment. AB - MCRS1 is involved in multiple cellular activities, including mitotic spindle assembly, mTOR signaling and tumorigenesis. Although MCRS1 has been reported to bind to the dynein regulator NDE1, a functional interaction between MCRS1 and cytoplasmic dynein remains unaddressed. Here, we demonstrate that MCRS1 is required for dynein-dependent cargo transport to the centrosome and also plays a role in primary cilium formation. MCRS1 localized to centriolar satellites. Knockdown of MCRS1 resulted in a dispersion of centriolar satellites whose establishment depends on cytoplasmic dynein. By contrast, NDE1 was not necessary for the proper distribution of centriolar satellites, indicating a functional distinction between MCRS1 and NDE1. Unlike NDE1, MCRS1 played a positive role for the initiation of ciliogenesis, possibly through its interaction with TTBK2. Zebrafish with homozygous mcrs1 mutants exhibited a reduction in the size of the brain and the eye due to excessive apoptosis. In addition, mcrs1 mutants failed to develop distinct layers in the retina, and showed a defect in melatonin induced aggregation of melanosomes in melanophores. These phenotypes are reminiscent of zebrafish dynein mutants. Reduced ciliogenesis was also apparent in the olfactory placode of mcrs1 mutants. Collectively, our findings identify MCRS1 as a dynein-interacting protein critical for centriolar satellite formation and ciliogenesis. PMID- 27263858 TI - Comb-locked Lamb-dip spectrometer. AB - Overcoming the Doppler broadening limit is a cornerstone of precision spectroscopy. Nevertheless, the achievement of a Doppler-free regime is severely hampered by the need of high field intensities to saturate absorption transitions and of a high signal-to-noise ratio to detect tiny Lamb-dip features. Here we present a novel comb-assisted spectrometer ensuring over a broad range from 1.5 to 1.63 MUm intra-cavity field enhancement up to 1.5 kW/cm(2), which is suitable for saturation of transitions with extremely weak electric dipole moments. Referencing to an optical frequency comb allows the spectrometer to operate with kHz-level frequency accuracy, while an extremely tight locking of the probe laser to the enhancement cavity enables a 10(-11) cm(-1) absorption sensitivity to be reached over 200 s in a purely dc direct-detection-mode at the cavity output. The particularly simple and robust detection and operating scheme, together with the wide tunability available, makes the system suitable to explore thousands of lines of several molecules never observed so far in a Doppler-free regime. As a demonstration, Lamb-dip spectroscopy is performed on the P(15) line of the 01120 00000 band of acetylene, featuring a line-strength below 10(-23) cm/mol and an Einstein coefficient of 5 mHz, among the weakest ever observed. PMID- 27263859 TI - Integrated ultracompact and broadband wavelength demultiplexer based on multi component nano-cavities. AB - Integrated nanoscale photonic devices have wide applications ranging from optical interconnects and optical computing to optical communications. Wavelength demultiplexer is an essential on-chip optical component which can separate the incident wavelength into different channels; however, the experimental progress is very limited. Here, using a multi-component nano-cavity design, we realize an ultracompact, broadband and high-contrast wavelength demultiplexer, with 2.3 MUm feature size, 200 nm operation bandwidth (from 780 nm to 980 nm) and a contrast ratio up to 13.7 dB. The physical mechanism is based on the strong modulation of the surface plasmon polaritons induced by the multi-component nano-cavities, and it can be generalized to other nanoscale photonic devices. This provides a strategy for constructing on-chip photon routers, and also has applications for chip-integrated optical filter and optical logic gates. PMID- 27263860 TI - Postoperative improvement in DASH score, clinical findings, and nerve conduction velocity in patients with cubital tunnel syndrome. AB - We investigated a recovery pattern in subjective and objective measures among 52 patients with cubital tunnel syndrome after anterior subcutaneous transposition of the ulnar nerve. Disabilities of the Arm, Shoulder and Hand (DASH) score (primary outcome), numbness score, grip and pinch strength, Semmes-Weinstein (SW) score, static 2-point discrimination (2PD) score, and motor conduction velocity (MCV) stage were examined preoperatively and 1, 3, 6, 12, and >=24 months postoperatively. Statistical analyses were conducted to evaluate how each variable improved after surgery. A linear mixed-effects model was used for continuous variables (DASH score, numbness, grip and pinch strength), and a proportional odds model was used for categorical variables (SW and 2PD tests and MCV stages). DASH score significantly improved by 6 months. Significant recovery in numbness and SW test scores occurred at 1 month. Grip and pinch strength, 2PD test scores, and MCV stage improved by 3 months. DASH scores and numbness recovered regardless of age, sex, or disease severity. It was still unclear if both subjective and objective measures improved beyond 1-year postoperatively. These data are helpful for predicting postoperative recovery patterns and tend to be most important for patients prior to surgery. PMID- 27263861 TI - Ultrahigh photoconductivity of bandgap-graded CdSxSe1-x nanowires probed by terahertz spectroscopy. AB - Superiorly high photoconductivity is desirable in optoelectronic materials and devices for information transmission and processing. Achieving high photoconductivity via bandgap engineering in a bandgap-graded semiconductor nanowire has been proposed as a potential strategy. In this work, we report the ultrahigh photoconductivity of bandgap-graded CdSxSe1-x nanowires and its detailed analysis by means of ultrafast optical-pump terahertz-probe (OPTP) spectroscopy. The recombination rates and carrier mobility are quantitatively obtained via investigation of the transient carrier dynamics in the nanowires. By analysis of the terahertz (THz) spectra, we obtain an insight into the bandgap gradient and band alignment to carrier transport along the nanowires. The demonstration of the ultrahigh photoconductivity makes bandgap-graded CdSxSe1-x nanowires a promising candidate as building blocks for nanoscale electronic and photonic devices. PMID- 27263862 TI - Range expansion of the Bluetongue vector, Culicoides imicola, in continental France likely due to rare wind-transport events. AB - The role of the northward expansion of Culicoides imicola Kieffer in recent and unprecedented outbreaks of Culicoides-borne arboviruses in southern Europe has been a significant point of contention. We combined entomological surveys, movement simulations of air-borne particles, and population genetics to reconstruct the chain of events that led to a newly colonized French area nestled at the northern foot of the Pyrenees. Simulating the movement of air-borne particles evidenced frequent wind-transport events allowing, within at most 36 hours, the immigration of midges from north-eastern Spain and Balearic Islands, and, as rare events, their immigration from Corsica. Completing the puzzle, population genetic analyses discriminated Corsica as the origin of the new population and identified two successive colonization events within west Mediterranean basin. Our findings are of considerable importance when trying to understand the invasion of new territories by expanding species. PMID- 27263863 TI - New Method for Sorting Endothelial and Neural Progenitors from Human Induced Pluripotent Stem Cells by Sedimentation Field Flow Fractionation. AB - Human induced pluripotent stem cells (hiPSc) are a very useful solution to create and observe the behavior of specific and usually inaccessible cells, such as human motor neurons. Obtained from a patient biopsy by reprograming dermal fibroblasts (DF), hiPSc present the same properties as embryonic stem cells and can generate any cell type after several weeks of differentiation. Today, there are numerus protocols which aim to control hiPSC differentiation. The principal challenge is to obtain a sufficiently enriched specific cell population to study disease pathophysiology and to provide a good model for further investigation and drug screening. The differentiation process is very costly and time-consuming, because many specific factors and different culture media must be used. In this study, we used Sedimentation Field Flow Fractionation (SdFFF) to prepare enriched populations derived from hiPSc after only 10 days of culture in a classical medium. Based on phenotypic and proteomic characterization, "hyperlayer" elution resulted in a fraction expressing markers of endothelial progenitors while another fraction expressed markers of neural progenitors. The isolation of subpopulations representing various differentiation lineages is of major interest for the production of specialized, cell-enriched fractions and in the preparation of increasingly complex models for the development of new therapeutic tools. PMID- 27263864 TI - Sorbent Mass Variation Method: A New Possibility for the Determination of Binding Isotherms. AB - Measurement of equilibrium mass fraction of a surfactant as a function of the sorbent mass fraction was performed on gel sorbent-solution systems in order to determine binding isotherms and to calculate fundamental characteristics of the solvation layer. With application of this new method, it was possible to calculate specific solvation/sorption capacity and absolute average local composition of the solvation layer. It has been pointed out by systematic variation of the composition (hydrophobicity) and degree of cross-linking of the gel sorbents that the ratio of components in the solvation layer can be constant in a given range of equilibrium mass fraction of the sodium dodecyl sulfate (SDS) and that the specific solvation/sorption capacity of gel sorbents can be much greater than that of activated carbon type adsorbents. On the basis of a mixed sorbent model, it turned out from calculations that there is no preferential binding of SDS close to the chemical cross-links and that the surfactant molecules prefer vinyl acetate groups as binding sites. The density of cross links regulates the aggregation number of the bound surfactant as well. For loose gels, both binding isotherms and swelling curves show that the surfactant-polymer interaction is a strongly cooperative process. The result of these experiments may influence the general concept of solvation/sorption isotherms and all related phenomena. PMID- 27263865 TI - Silver-Lactoferrin Nanocomplexes as a Potent Antimicrobial Agent. AB - The process of silver immobilization onto and/or into bovine lactoferrin (LTF), the physicochemical properties of bovine lactoferrin and obtained silver lactoferrin complexes, as well as antibacterial activity of silver-lactoferrin complexes were investigated in this work. Kinetic study of the silver immobilization into lactoferrin was carried out using batch sorption techniques. Spectrometric (MALDI-TOF/TOF-MS, ICP-MS), spectroscopic (FTIR, SERS), electron microscopic (TEM) and electrophoretic (I-DE) techniques, as well as zeta potential measurements, were applied for characterization of LTF and binding nature of silver in Ag-LTF complexes. On the basis of the results of the kinetics study, it was established that the silver binding to LTF is a heterogeneous process involving two main stages: (i) internal diffusion and sorption onto external surface of lactoferrin globules; and (ii) internal diffusion and binding into lactoferrin globule structure. Spectroscopic techniques combined with TEM analysis confirmed the binding process. Molecular dynamics (MD) analysis was carried out in order to simulate the mechanism of the binding process, and locate potential binding sites, as well as complement the experimental findings. Quantum mechanics (QM) simulations were performed utilizing density functional theory (DFT) in order to support the reduction mechanism of silver ions to elemental silver. Antimicrobial activity of synthesized lactoferrin complexes against selected clinical bacteria was confirmed using flow cytometry and antibiograms. PMID- 27263866 TI - Perceptions of diabetes control among people with type 2 diabetes treated with basal insulin in Sweden, Switzerland, and the United Kingdom. AB - OBJECTIVE: To investigate perceptions of control among people with uncontrolled and well controlled type 2 diabetes (T2D) treated with basal insulin, as well as differences in perceptions and diabetes management practices between the two groups. RESEARCH DESIGN AND METHODS: Web surveys of 1012 people with uncontrolled T2D (HbA1c >8.0% or 64 mmol/mol) on basal insulin in Sweden, Switzerland, and the UK and 295 people with well controlled T2D (HbA1c <7.5% or 58 mmol/mol) on basal insulin in the UK were conducted. RESULTS: People with uncontrolled T2D perceived a wide range of factors as very/extremely important for deciding whether they are well controlled, including diet (80.7%), HbA1c value (78.9%), times per day insulin taken (78.8%), insulin units taken per day (77.6%), and energy levels (74.5%). Fifty-one percent of uncontrolled respondents considered the past week or more recently when thinking about control. Perceived major obstacles to control included stress (75.4%), other health issues (70.8%), medicine side effects (69.9%), food cravings (69.8%), doctor not understanding individual situation (67.6%), and life crises (66.9%). Many uncontrolled respondents reported that diabetes was very/extremely interfering with their lives, including energy level (71.0%), performance at work (70.0%), general health (69.9%), and doing what one wants (69.3%). Analyses showed significant differences between well controlled and uncontrolled UK respondents. Compared to the uncontrolled, people with well controlled T2D were significantly more likely to consider the last 24 hours/current time when thinking about control (50% vs. 21%, p < 0.001) and reported greater healthcare contact related to diabetes and more frequent glucose measurement. Study limits include potential selection bias of web surveys and possible recall bias in patient-reported data. CONCLUSIONS: The results illuminate how people with T2D treated with basal insulin perceive control and show important differences between the well controlled and uncontrolled. Findings may have implications for improving patient and physician education and diabetes management. PMID- 27263867 TI - Detecting nonvalvular atrial fibrillation and anticoagulant therapy in cardioembolic ischemic stroke. AB - Nonvalvular Atrial fibrillation (NVAF) is the most common cardiac arrhythmia associated with an increase in risk of stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home. The present review will focus on the current status of detecting NVAF and stroke prevention when there is AF. The CHA2DS2-VASc risk stratification scheme is discussed for the identification of patients who are at risk for thromboembolic stroke related to NVAF. Patient with a CHA2DS2-VASc score of 2 or greater are candidates for warfarin or a novel oral anticoagulant, irrespective of whether the strategy is for rate or rhythm control. Finally, guidelines and landmark clinical trials in NVAF patients with primary or secondary stroke prevention are discussed. PMID- 27263869 TI - Changing Adjuvant Breast-Cancer Therapy with a Signal for Prevention. PMID- 27263868 TI - Risk of major depressive disorder among older persons living in HIV-endemic central and southwestern Uganda. AB - Major depressive disorder (MDD) is projected to become the second most common cause of disability by 2020 calling for a better understanding its antecedents across the lifespan and in diverse socio-cultural settings. In this paper we describe the risk factors of MDD among older people (50 years +) living in HIV endemic central and southwestern Uganda. A cross-sectional study was undertaken among 471 respondents (50 years +) participating in the Wellbeing of Older People's Study cohort of the MRC/UVRI Uganda research Unit on AIDS in Uganda. Participants were from five strata: HIV negative, HIV positive on ART, HIV positive not on ART, having an adult child on ART, and having an adult child who died of HIV. Overall MDD prevalence was 9.2% (95% CI 6.7-12.2%) with a prevalence among males of 7.4% (95% CI 4.0-12.3%) and females of 10.3% (95% CI 7.0-14.3%). Factors significantly associated with MDD included: declining socio-economic status, increasing disability scores, decreasing mean grip strength, reported back pain, and not having hypertension. Marginally associated with MDD was being HIV infected and not on ART. PMID- 27263933 TI - High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer's disease. AB - BACKGROUND: Increased concentrations of cerebrospinal fluid (CSF) total tau (t tau) and phosphorylated tau, as well as decreased amyloid-beta 42 peptide, are biomarkers of Alzheimer's disease (AD) pathology, but few studies have shown an association with AD progression rate. We hypothesized that high CSF tau, as a marker of ongoing neurodegeneration, would predict a more aggressive course of AD, using time to nursing home placement (NHP) as the main outcome. METHODS: Our sample inlcuded 234 patients with mild cognitive impairment (MCI) due to AD (n = 134) or mild to moderate AD (n = 100) who underwent lumbar puncture at a memory clinic and were followed for 2-11 years (median 4.9 years). RESULTS: Individuals with CSF t-tau in the highest quartile (>=900 ng/L) had a higher ratio of NHP, both in the total cohort and in patients with MCI only (adjusted HR 2.17 [95% CI 1.24-3.80]; HR 2.37 [95% CI 1.10-5.09], respectively), than the lowest quartile. The association between high t-tau levels and future steep deterioration was confirmed in analyses with conversion to moderate dementia (HR 1.66; 95% CI 1.08 2.56), rapid decline in Mini Mental State Examination score (>=4-point drop/12 months), and dying in severe dementia as outcomes. CONCLUSIONS: To our knowledge, this is the first study to show that high CSF t-tau levels predict early NHP and conversion to moderate dementia in an AD cohort. Selecting patients with high CSF t-tau, indicating more aggressive neurodegeneration and steeper decline, for AD immunotherapy trials might increase the possibility of showing contrast between active treatment and placebo. PMID- 27263934 TI - Targeting Notch degradation system provides promise for breast cancer therapeutics. AB - Notch receptor signaling pathways play an important role, not only in normal breast development but also in breast cancer development and progression. As a group of ligand-induced proteins, different subtypes of mammalian Notch (Notch1 4) are sensitive to subtle changes in protein levels. Thus, a clear understanding of mechanisms of Notch protein turnover is essential for understanding normal and pathological mechanisms of Notch functions. It has been suggested that there is a close relationship between the carcinogenesis and the dysregulation of Notch degradation. However, this relationship remains mostly undefined in the context of breast cancer, as protein degradation is mediated by numerous signaling pathways as well as certain molecule modulators (activators/inhibitors). In this review, we summarize the published data regarding the regulation of Notch family member degradation in breast cancer, while emphasizing areas that are likely to provide new therapeutic modalities for mechanism-based anti-cancer drugs. PMID- 27263936 TI - The importance of protein profiling in the diagnosis and treatment of hematologic malignancies. AB - Proteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemia-associated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed. PMID- 27263935 TI - Neurofibromatosis type 1 associated low grade gliomas: A comparison with sporadic low grade gliomas. AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder, associated with a variable clinical phenotype including cafe-au-lait spots, intertriginous freckling, Lisch nodules, neurofibromas, optic pathway gliomas and distinctive bony lesions. NF1 is caused by a mutation in the NF1 gene, which codes for neurofibromin, a large protein involved in the MAPK- and the mTOR-pathway through RAS-RAF signalling. NF1 is a known tumour predisposition syndrome, associated with different tumours of the nervous system including low grade gliomas (LGGs) in the paediatric population. The focus of this review is on grade I pilocytic astrocytomas (PAs), the most commonly observed histologic subtype of low grade gliomas in NF1. Clinically, these PAs have a better prognosis and show different localisation patterns than their sporadic counterparts, which are most commonly associated with a KIAA1549:BRAF fusion. In this review, possible mechanisms of tumourigenesis in LGGs with and without NF1 will be discussed, including the contribution of different signalling pathways and tumour microenvironment. Furthermore we will discuss how increased understanding of tumourigenesis may lead to new potential targets for treatment. PMID- 27263937 TI - Determination of apoptosis, proliferation status and O6-methylguanine DNA methyltransferase methylation profiles in different immunophenotypic profiles of diffuse large B-cell lymphoma. AB - OBJECTIVE: Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid), apoptotic index (AI) and proliferation index (PI) in germinal center B-cell-like immunophenotypic profile (GCB) and non GCB of diffuse large B-cell lymphoma (DLBCL). METHODS: The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunophenotypic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases) or non-GCB (72 cases). Apoptosis-associated proteins and PI were determined by IHC, and TUNEL method was used to determine AI. MGMT methylation analysis was performed by real-time PCR. RESULTS: The PI was significantly higher in GCB compared with non-GCB (p=0.011). Percentage of cells stained with bcl-6 was positively correlated with the percentage of cells expressing bcl-2 (p=0.023), AI (p=0.006) and PI (p<0.001), while a significant negative correlation was observed with the percentage of cells expressing bax (p=0.027). The percentage of cells stained with MUM1 showed a significantly positive correlation with the percentage of cells expressing bcl-xl (p=0.003), bid (p=0.002), AI (p<0.001), and PI (p=0.001). MGMT methylation analysis was performed in 95 samples, and methylated profile was found in 31 cases (32.6%). GCB was found in 6 cases (22.2%) and non-GCB was determined in 25 cases (36.8%) out of 31 with MGMT methylated samples. There was no significant association between MGMT methylation status and immunophenotypic profiles (p=0.173). CONCLUSION: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB. Additionally, we found that apoptosis associated proteins were not significantly associated with immunophenotypic profiles. PMID- 27263938 TI - The relation between soluble endothelial protein C receptor and factor VIII levels and FVIII/sEPCR index in healthy infants. AB - OBJECTIVE: Both soluble endothelial protein C receptor (sEPCR) and factor VIII (FVIII) seem to be potential mediators in thrombotic and inflammatory states. The aim of the present study was to determine the relation between plasma sEPCR and FVIII levels in a group of healthy Turkish infants. METHODS: The study population consisted of 50 healthy infants aged 6 months (Group 1, n=23) and 12 months (Group 2, n=27) having no acute or chronic infection and/or disease. sEPCR levels and FVIII levels were measured by ELISA and one stage factor assay method, respectively. RESULTS: The sEPCR levels of the infants aged 6 months were found higher than those of the infants aged 12 months (p<0.001). There was a correlation between sEPCR and FVIII levels of the infants in Group 1 (6-month-old infants) (r=0.678, p<0.001). FVIII/sEPCR index was 0.73+/-0.3 and 1.0+/-0.5 in Group 1 and Group 2, respectively (p=0.027). A correlation between infant age and FVIII/sEPCR index was found (r=0.312, p=0.027). CONCLUSION: The FVIII/sEPCR index in healthy infants reflects the physiological condition of this population. The finding showing a positive relationship between sEPCR and FVIII levels suggests a possible interaction between these mediators in healthy infants aged six months. PMID- 27263939 TI - Differences in lymphocyte subpopulation count and function in cord, maternal and adult blood. AB - OBJECTIVE: Phenotypical characterization and functional activity of lymphocytes and natural killer (NK) cells in cord blood (CB) were investigated, and maternal peripheral blood (MPB) values were compared to those of adult peripheral blood (APB) (control). METHODS: To determine cytotoxic activity target cells (K562) were labeled with carboxyfluorescein diacetate (CFDA) or fluorescein isothiocyanate (FITC), and propidium iodide (PI) was used to label dead cells. Cell surface expression in CB, APB, and MPB cells were analyzed using flow cytometry. RESULTS: CB and MPB mononuclear cells had similar CD45, CD34, CD4, and surface molecule for T helper cell expression, but had low-level expression of total T-lymphocyte surface molecules CD3 and CD8. CD19 and HLA-DR expression was higher in CB than in MPB. The same high-level of expression for CD19 and HLA-DR was observed in APB, as compared to MPB. All other cell surface expressions were similar in APB and MPB samples. NK (CD16+ and CD56+) cells in CB was similar to that in MPB and APB, and the level of inhibitory KIR receptors in NK cells was higher in venous CB than in MPB and APB. The only difference between MPB and APB was that the CD158a level was higher in MPB. No difference was observed in NK cells in CB and MPB, in terms of cytotoxicity. CONCLUSION: The present results show that there was numerical and proportional variability of lymphocytes and their subgroups in CB and APB, but no cytological difference. PMID- 27263940 TI - Evaluation of oxidative status in iron deficiency anemia through total antioxidant capacity measured using an automated method. AB - OBJECTIVE: Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of iron deficiency anemia. The objective of this study was to evaluate the oxidative status and to determine whether there is any relationship between oxidative status and the severity of anemia in patients with iron deficiency anemia using an automated method. METHODS: Twenty-six subjects with iron deficiency anemia and 20 healthy controls were enrolled in the present study. Serum total antioxidant capacity, serum total peroxide level and oxidative stress index were determined in all study subjects. RESULTS: Serum total antioxidant capacity was significantly lower in patients with iron deficiency anemia than controls (p<0.05), while serum total peroxide level and oxidative stress index were significantly higher (both p<0.05). There was a significant correlation between hemoglobin level and serum total peroxide level, oxidative stress index and total antioxidant capacity (r=-0.504, p<0.05; r=-0.503, p<0.05; r=0.417, p<0.05, respectively). CONCLUSION: Increased oxidative stress may play a role in the pathogenesis of iron deficiency anemia. Supplementation of antioxidant vitamins in conjunction with iron replacement therapy may offer better responses and provide early resolution of symptoms related to iron deficiency anemia. The automated assay is a reliable and easily applied method for measurement of serum total antioxidant capacity in iron deficiency anemia. PMID- 27263942 TI - Hyperuricemia and tumor lysis syndrome in children with non-Hodgkin's lymphoma and acute lymphoblastic leukemia. AB - OBJECTIVE: This study aimed to examine the incidence, clinical characteristics, and outcome of hyperuricemia and tumor lysis syndrome (TLS) in children with non Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL). METHODS: This retrospective study included data from 327 patients (113 NHL and 214 ALL). RESULTS: Hyperuricemia occurred in 26.5% and 12.6% of the patients with NHL and ALL, respectively. The corresponding figures for TLS were 15.9% and 0.47% (p=0.001). All hyperuricemic NHL patients had advanced disease and renal involvement was present in 53%. All hyperuricemic ALL patients had a leukocyte count >50,000 mm3 at the time of diagnosis. Among the hyperuricemic NHL and ALL patients, 96.6% and 66.6% had LDH >=500 UI/L, respectively. Treatment consisted of hydration and allopurinol; none of the patients received urate oxidase. Among the patients that developed TLS, 26.3% had laboratory TLS, 42.1% had grade I or II TLS, and 31.6% had grade III or IV TLS. Uric acid levels returned to normal after a mean period of 3.5+/-2.5 and 3.05+/-0.8 d in NHL and ALL groups, respectively. In all, 7% of the patients with hyperuricemia required hemodialysis. None of the patients died. CONCLUSION: In this series the factors associated with a high-risk for TLS were renal involvement in NHL and high leucocyte count in ALL. Management with allopurinol and hydration was effective in this group of patients with high tumor burden. PMID- 27263941 TI - Seroprevalence and genotyping of hepatitis C virus in multiple transfused Jordanian patients with beta-thalassemia major. AB - OBJECTIVE: The main objectives of this study are to investigate the prevalence of HCV among patients with beta-thalassemia major and to determine the most prevalent genotype for this virus among them. METHODS: One hundred twenty-two beta-thalassemia major patients who were previously diagnosed at the molecular level were included. All plasma samples were tested for the presence of antibodies by ELISA. Real-time polymerase chain reaction (PCR) was used in the quantitation the HCV RNA viral loads, and consequently, patients with high virus titer were genotyped by the linear array. RESULTS: Forty of the patients were anti-HCV positive. The prevalence of anti-HCV was significantly higher in patients who received blood transfusion before 1993 (83.7%) than in those who received it after 1993 (16.3%) (p=0.000). beta-thalassemia major patients with HCV infection had significantly higher rates of elevated aspartate aminotransferase (54.4% vs 40.5%, p=0.045) and alanine aminotransferase (72.47% vs 37.47%, p=0.00) and of splenectomy (54.8% vs 45.2%, p=0.004) than beta thalassemia major patients without HCV. CONCLUSION: HCV genotype 4 is the commonest genotype in multi-transfused patients with beta-thalassemia major in Jordan. PMID- 27263943 TI - PET CT imaging in extramedullary hematopoiesis and lung cancer surprise in a case with thalassemia intermedia. AB - Extramedullary hematopoiesis (EMH) is the production of hematopoietic precursors outside the bone marrow cavity, and it causes mass effects according to its localization. Magnetic resonance imaging (MRI) and/or computed tomography (CT) scans are used most commonly to detect EMH foci. We report herein a case with thalassemia intermedia causing paravertebral mass associated with EMH detected by CT scan. We further evaluated the case with positron emission tomography (PET) CT, and lung cancer, which was not revealed in the CT scan, was detected coincidentally. PMID- 27263944 TI - Treatment of intrathecal methotrexate overdose with folinic acid rescue and lumbar cerebrospinal fluid exchange: A report of two cases. AB - We report two male cases (4- and 5-years-old) of intrathecal methotrexate overdose. The two boys with acute lymphoblastic leukemia were to receive intrathecal injection of methotrexate. Instead of the prescribed 12 mg, they both received a dose of 120 mg. The initial cerebrospinal fluid samples showed methotrexate concentration of 2.24x10-2M in case 1 and 1.32x10-2M in case 2. The cases were successfully treated with cerebrospinal fluid (CSF) exchange and intravenous folinic acid rescue. The favorable outcome in our cases suggests that CSF exchange is safe and that folinic acid rescue may be adequate to prevent sequelae in patients subjected to intrathecal MTX overdoses up to 120 mg. We propose CSF exchange and intravenous folinic acid as the mainstay of treatment. In addition to the staff's failure to check the drug label carefully, the marked resemblance of the two dose preparations of MTX may have been contributory. PMID- 27263945 TI - Brucellosis presenting with pancytopenia due to hemophagocytic syndrome. AB - Reactive hemophagocytic syndrome is clinically characterized by fever, hepatosplenomegaly, pancytopenia, and coagulopathy, and is histologically characterized by excessive proliferation and activation of histiocytes or macrophages. It can occur with systemic infections, immunodeficiency, or underlying malignancy. Brucellosis is one of the rare causes of hemophagocytosis. Herein we report an 11-year-old male with pancytopenia due to hemophagocytosis during the course of brucellosis that responded favorably to therapy. Although rare, hemophagocytosis should be considered as a possible cause of pancytopenia in patients with brucellosis, especially in regions where brucellosis is frequently encountered. PMID- 27263946 TI - A child with primary gastric lymphoma and cavernous sinus involvement. PMID- 27263947 TI - Feasibility of four discriminant functions for identifying hemoglobin E disorders: Experience in 114 Thai pregnant subjects. PMID- 27263948 TI - The association between calcium dobesilate and pancytopenia in type 2 diabetes: A case report. PMID- 27263949 TI - Aeromonas sobria bacteriemia in an acute lymphoblastic leukemia case in remission. PMID- 27263950 TI - ARA-C associated pulmonary toxicity. PMID- 27263951 TI - Niemann-Pick disease. PMID- 27263952 TI - Enough With Polio: It's Measles' Turn Now in Pakistan. PMID- 27263953 TI - A review of abnormal hemoglobins in Turkey. AB - In this review, abnormal hemoglobins published in Turkish population during the last 4 years are presented. Further, analysis of the 88 abnormal hemoglobins is geven. PMID- 27263954 TI - Beta globin gene cluster haplotypes of abnormal hemoglobins observed in Turkey. AB - Since the first observation of hemoglobin S (Hb S) in Turkey by Aksoy, the number of hemoglobin variants reported was increased. Beta globin gene cluster haplotypes are being used to determine the origin of the mutations under interest. We studied the beta globin gene cluster haplotypes for the six different abnormal hemoglobins which are Hb S, Hb D-Los Angeles, Hb G-Coushatta, Hb E, Hb E-Saskatoon and Hb J-Iran observed in Turkey. In this study, we report two novel haplotypes [- + + - - - +] and [- + - + + +] in association with the Hb G-Coushatta mutation. The haplotype for the Hb J-Iran is also reported as [- + - + + + +] for the first time in world populations from Turkey. PMID- 27263955 TI - The effects of platelet receptor GPIIb/IIIa polymorphism (Leu Pro33) on the receptor expression and platelet aggregation in patients with ischaemic stroke. AB - Platelet hyperaggregation in ischaemic stroke patients is a proven finding, and associated with increased expression of the platelet surface GPIIb/IIIa receptor. The polymorphism occurs at nucleotide position 1565 of the GPIIIa gene resulting a 33Leu-Pro change. Data are conflicting regarding the abnormal function of the PlA1/A2 receptor in stroke. The aim of the study was to address the difference of platelet receptor function in ischemic stroke patients with the wild PlA1/A1 and heterozygous PlA1/A2 genotype. A total of 51 patients with PA1/A1 and 54 patients with PlA1/A2 genotypes were enrolled. Polymerase chain reaction was used for genotyping of platelets. Platelet aggregation was measured in whole blood and in platelet rich plasma (PRP). Flow cytometry was used for measuring surface molecule expression (CD42b, CD41a, CD61, CD62P) and fibrinogen binding capacity of cells with phosphate buffer solution (PBS) in comparison with activation by ristocetin in whole blood as well as by adenosine diphosphate (ADP) in PRP. In comparison with wild types, platelets carrying the PlA1/A2 genotypes showed hyperaggregation measured in whole blood and induced by ristocetin (p< 0.05). Using whole blood flow cytometry with ristocetin induction, the CD62P+/FIB- (P selectin) and the CD62P+/FIB+ were more expressed in heterozygous platelets as compared to wild types (p< 0.01 and p< 0.05), respectively. According to mean fluorescence intensity with ADP induction, an increased expression of CD61+, CD61+/CD41+ and CD62P+ in PlA1/A2 platelets were detected as compared to the group carrying the wild type (p< 0.0001, p= 0.006, p= 0.0001), respectively. These findings support the possibility that in ischaemic stroke patients, platelets carrying PlA1/A2 genotypes can be activated by different inductors in a way, which leads to permanent hyperfunction of platelet surface receptor GPIIIa. PMID- 27263956 TI - Public education for the prevention of hemoglobinopathies: a study targeting Kocaeli University students. AB - In addition to premarital screening programs, education of the general population is important in preventing hemoglobinopathies. The aim of the present study was the education of university students. Short questionnaires were applied before and after a prepared lecture. A 20-minute audiovisual education was provided including the clinical characteristics and inheritance of thalassemia and sickle cell anemia (SCA) as well as the importance of carrier screening. The attendance to 42 lectures was low (n= 1348 = 5%). Seventy-four percent of the students had heard of thalassemia. The percentage of the students who had some accurate knowledge was 25% for thalassemia and 11.7% for SCA. Following the lecture, these numbers increased to 86.2% and 72.1% for thalassemia and SCA, respectively. Only 13.6% of the students were aware of the risk of being carriers, but this increased to 78.6% following the lecture; 92.4% learned that these hemoglobinopathies were inherited and 78.8% learned that consanguineous marriages would increase the risk. Education on hemoglobinopathies must be integrated into the curricula of middle schools and high schools. PMID- 27263957 TI - Relationship between activation and apoptosis in platelets. AB - Phosphatidylserine (PS) externalization is a marker for the nucleated cell apoptosis, and refers cellular activation rather than apoptosis in platelets. On the other hand, several similarities exist between platelet activation and apoptosis in nucleated cells. Herewith we investigated the relationship between platelet activation and platelet apoptosis. Platelets isolated from fresh blood of 22 healthy volunteers were incubated with and without calcium ionophore A23187. Platelet activation was evaluated with CD62P and CD63 antibodies, whereas apoptosis with intracellular anti caspase 3-antibody and JC-1 cationic dye. In order to detect PS externalization we used Annexin V by flow cytometry at the beginning, 20th min and 5th hours of the incubation, respectively. There were positive correlations between caspase-3 activation and PS externaization, ?Psim depolarization, CD63, and also between PS externaization and CD62P in incubations with A23187 at 5th hours of incubations. These results suggest that there is a relationship between activation and apoptosis in platelets, and platelet activation may progress to platelet apoptosis. PMID- 27263958 TI - Spinal epidural extramedullary hematopoiesis during the complicated course of polycythemia vera. AB - Extramedullary hematopoiesis (EMH) may uncommonly develop during the course of polycythemia vera (PV). We herein present a 57-year-old patient with spinal epidural EMH that developed during the complicated course of PV and his outcome under different treatment modalities including hydroxyurea, 32P, radiotherapy and surgery. PMID- 27263959 TI - Malignant myelomatous pleural effusion-Is onset of effusion a new prognostic factor? AB - Malignant pleural effusion in myeloma (MMPE) is a rare terminal event; with a median survival is four months. All the patients usually have multiple poor prognostic factors and none of them (like beta 2-microglobulin, karyotype, Stage of disease, C-reactive protein etc.) correctly predicts the survival. We are reporting a series of five cases and evaluated the factors influencing the overall survival. All of our patients had a very good response to treatment and had a better survival compared to the reported cases so far. After reviewing the literature carefully we found that timing of development of pleural effusion is probably the most important prognostic factor. Those who develop effusion after some time lag form the initial treatment, will have a poor survival (median four months) compared to those who had effusion at the start of the disease. PMID- 27263961 TI - A book on Ord. Prof. Dr. Erich Frank. PMID- 27263960 TI - Retrospective analysis of seven patients with adult-onset langerhans cell histiocytosis syndromes: A single center experience. PMID- 27263962 TI - Physiological and pharmacokinetic effects of multilevel caging on Sprague Dawley rats under ketamine-xylazine anesthesia. AB - While the cage refinement is a necessary step towards improving the welfare of research rats, increasing the complexity and surface area of the living space of an animal may have physiological impacts that need to be taken into consideration. In this study, ketamine (80 mg/kg) and xylazine (10 mg/kg) caused a short duration anesthesia that was significantly decreased in Sprague-Dawley rats housed in multilevel cages (MLC), compared to rats housed in standard cages (SDC). The withdrawal reflex, the palpebral reflexes and the time-to-sternal all occurred earlier in MLC housed rats, suggesting an effect of housing on the physiology of the rats. In addition, during anesthesia, cardiac frequencies were increased in animals housed in the smaller SDC. Respiratory frequencies, the blood oxygen saturation and rectal temperatures during anesthesia did not vary between conditions during the anesthesia. While xylazine pharmacokinetics were unchanged with caging conditions, the clearance and half-lives of ketamine and its metabolite, norketamine, were altered in the rats housed in MLC. Finally, while no difference was ultimately seen in rat body weights, isolated liver and adrenal gland weights were significantly lighter in rats housed in the MLC. Increasing cage sizes, while having a positive impact on wellbeing in rats, can alter anesthetic drug metabolism and thus modify anesthesia parameters and associated physiological processes. PMID- 27263964 TI - Role of physical activity in the management and assessment of rheumatoid arthritis patients. AB - OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting diarthrodial joints, in which patients tend to perform less physical activity (PA) than recommended. This review focuses on the existing evidence about the relationship of PA and RA, specifically how the former influences joint inflammation, disability, quality of life and pain in RA patients, and also how disease activity potentially impacts PA in these patients. METHODS: A literature search of EMBASE and MEDLINE databases from January 2000 to January 2015. RESULTS: The evidence indicating that PA in RA patients is safe and the benefits from regularly performing, both aerobic and resistance exercises, in these patients include improvement in: quality of life, functionality, pain and number of swollen joints. Interestingly, recent studies suggest that changes in disease activity in RA patients inversely correlate with variations in PA, as assessed by accelerometry. CONCLUSIONS: The regular monitoring of PA in RA patients might facilitate a more objective evaluation of variations in disease activity, helping physicians to make general and therapeutic recommendations that will improve both the health status and the joint functionality of these patients. PMID- 27263963 TI - Relapsed hydroxychloroquine induced thrombocytopenia in a systemic lupus erythematosus patient. AB - Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine. PMID- 27263966 TI - Current and novel approaches to treat patients presenting with ST elevation myocardial infarction. AB - INTRODUCTION: Primary percutaneous coronary intervention (PCI) represents the gold-standard treatment for patients presenting with an ST-elevation myocardial infarction (STEMI). Acute myocardial infarction is a complex clinical scenario, and an appropriate therapeutic approach could be represented by a balanced integration between healthcare system and medical competence. AREAS COVERED: In this review we discuss how a primary PCI network, and the new therapeutic options could be coupled in order to obtain improved clinical outcomes. The present report will focus on three main issues related to STEMI patients, namely, out of hospital management, primary PCI and pharmacological treatment. Expert commentary: A possible correct approach to a patient presenting a STEMI could be considered as a stepwise process, given by 5 steps: reducing the time to reperfusion; dual antiplatelet administration; radial access; new generation drug eluting stent implantation; long term management. PMID- 27263965 TI - Has joint involvement lessened in Kawasaki disease? AB - OBJECTIVE: Kawasaki disease (KD) is an acute systemic vasculitis affecting medium sized arteries, particularly the coronary arteries. Classic diagnosis is based in prolonged fever and different clinical features, including acute arthritis. Our objective is to determine the prevalence of arthritis at the moment of the diagnosis, the response to intravenous immunoglobulin infusion and the relation with cardiac findings. MATERIAL AND METHODS: Retrospective study through review of medical records of 42 patients with KD from 1988 to 2013. Demographic, clinical, laboratory variables and treatment were reviewed. RESULTS: Male sex was predominant (57%). Fever (100%), exanthema (92,9%), conjunctivitis (78,6%), oropharingeal changes (76,2%), cervical lymphadenopathy (71,4%), edema (52,4%) and peripheral desquamation (46,3%) were reported. Eight patients presented ecocardiography alterations (ectasia and aneurism). Acute articular involvement was reported in 7 (16%) patients, including oligoarticular (57%), monoarticular (29%) and polyarticular (14%) patterns. All patients had elevation of acute phase reactants with neutrophilia (57%) and hypoalbuminemia (71,5%), but showed a good therapeutic response to intravenous immunoglobulin, without sequelaes. Sixteen patients had incomplete KD nine males, with 100% of fever exanthema (75%), conjunctivitis (56%) and 50% of cervical lymphadenopathy. Whereas oropharingeal changes and edemas was described in 44% and 25% of them. Four patients with incomplete KD had coronary artery abnormalities. CONCLUSIONS: Acute arthritis was an uncommon finding (16%) and resulted in no sequelae. Maybe the treatment with intravenous immunoglobulin and aspirin prevents the development of articular abnormalities and then leading to a decrease in its follow-up requierement by reumathologist. The cardiovascular sequelae, mainly incomplete KD, remains determining its prognosis. The presence of articular involvement seems not to have influence over cardiac involvement. PMID- 27263967 TI - Clostridium difficile Infections in Children: Impact of the Diagnostic Method on Infection Rates. AB - BACKGROUND Polymerase chain reaction (PCR) assays based on the detection of the toxin B gene are replacing enzyme-linked immunosorbent assay (ELISA)-based toxin production detection or cell cytotoxicity assay in most laboratories. OBJECTIVE To determine the proportion of pediatric patients diagnosed with Clostridium difficile infection by PCR who would have also been diagnosed by ELISA and to compare the clinical characteristics of PCR+/ELISA+ vs PCR+/ELISA- patients. METHODS Using the microbiology laboratory information system, stool samples positive for C. difficile by PCR between October 2010 and July 2014 were identified. Using frozen stool specimens, an ELISA for toxin A and B was performed. A retrospective medical chart review was conducted to obtain demographic and clinical data. Duplicate samples were excluded. RESULTS A total of 136 PCR-positive samples underwent ELISA testing: 54 (40%) were positive for toxin A or B. The mean (SD) age of the entire cohort was 8.5 (6.2) years. There was no difference in age, gender, clinical manifestation, previous medical problems, and management between patients positive or negative by ELISA. However, patients positive by ELISA were more likely to have had a recent exposure to antibiotics (67.9% vs 50%; crude odds ratio, 2.1 [95% CI, 1.03-4.28]). CONCLUSION In our pediatric population, 60% of patients with C. difficile diagnosed by PCR had no toxin detectable by ELISA. ELISA-negative patients were less likely to have received an antibiotic recently compared with ELISA-positive patients. These results highlight the need to standardize laboratory criteria for the diagnosis of C. difficile infections in children. Infect Control Hosp Epidemiol 2016;37:1087-1093. PMID- 27263968 TI - Synaptic Rectification Controls Nonlinear Spatial Integration of Natural Visual Inputs. AB - A central goal in the study of any sensory system is to predict neural responses to complex inputs, especially those encountered during natural stimulation. Nowhere is the transformation from stimulus to response better understood than the vertebrate retina. Nevertheless, descriptions of retinal computation are largely based on stimulation using artificial visual stimuli, and it is unclear how these descriptions map onto the encoding of natural stimuli. We demonstrate that nonlinear spatial integration, a common feature of retinal ganglion cell (RGC) processing, shapes neural responses to natural visual stimuli in primate Off parasol RGCs, whereas On parasol RGCs exhibit surprisingly linear spatial integration. Despite this asymmetry, both cell types show strong nonlinear integration when presented with artificial stimuli. We show that nonlinear integration of natural stimuli is a consequence of rectified excitatory synaptic input and that accounting for nonlinear spatial integration substantially improves models that predict RGC responses to natural images. PMID- 27263969 TI - Hormonal Modulation of Pheromone Detection Enhances Male Courtship Success. AB - During the lifespans of most animals, reproductive maturity and mating activity are highly coordinated. In Drosophila melanogaster, for instance, male fertility increases with age, and older males are known to have a copulation advantage over young ones. The molecular and neural basis of this age-related disparity in mating behavior is unknown. Here, we show that the Or47b odorant receptor is required for the copulation advantage of older males. Notably, the sensitivity of Or47b neurons to a stimulatory pheromone, palmitoleic acid, is low in young males but high in older ones, which accounts for older males' higher courtship intensity. Mechanistically, this age-related sensitization of Or47b neurons requires a reproductive hormone, juvenile hormone, as well as its binding protein Methoprene-tolerant in Or47b neurons. Together, our study identifies a direct neural substrate for juvenile hormone that permits coordination of courtship activity with reproductive maturity to maximize male reproductive fitness. PMID- 27263970 TI - A Primate lncRNA Mediates Notch Signaling during Neuronal Development by Sequestering miRNA. AB - Long non-coding RNAs (lncRNAs) are a diverse and poorly conserved category of transcripts that have expanded greatly in primates, particularly in the brain. We identified an lncRNA, which has acquired 16 microRNA response elements for miR 143-3p in the Catarrhini branch of primates. This lncRNA, termed LncND (neurodevelopment), is expressed in neural progenitor cells and then declines in neurons. Binding and release of miR-143-3p by LncND control the expression of Notch receptors. LncND expression is enriched in radial glia cells (RGCs) in the ventricular and subventricular zones of developing human brain. Downregulation in neuroblastoma cells reduced cell proliferation and induced neuronal differentiation, an effect phenocopied by miR-143-3p overexpression. Gain of function of LncND in developing mouse cortex led to an expansion of PAX6+ RGCs. These findings support a role for LncND in miRNA-mediated regulation of Notch signaling within the neural progenitor pool in primates that may have contributed to the expansion of cerebral cortex. PMID- 27263972 TI - Orbitofrontal Cortex Value Signals Depend on Fixation Location during Free Viewing. AB - In the natural world, monkeys and humans judge the economic value of numerous competing stimuli by moving their gaze from one object to another, in a rapid series of eye movements. This suggests that the primate brain processes value serially, and that value-coding neurons may be modulated by changes in gaze. To test this hypothesis, we presented monkeys with value-associated visual cues and took the unusual step of allowing unrestricted free viewing while we recorded neurons in the orbitofrontal cortex (OFC). By leveraging natural gaze patterns, we found that a large proportion of OFC cells encode gaze location and, that in some cells, value coding is amplified when subjects fixate near the cue. These findings provide the first cellular-level mechanism for previously documented behavioral effects of gaze on valuation and suggest a major role for gaze in neural mechanisms of valuation and decision-making under ecologically realistic conditions. PMID- 27263971 TI - Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord. AB - Circuit function in the CNS relies on the balanced interplay of excitatory and inhibitory synaptic signaling. How neuronal activity influences synaptic differentiation to maintain such balance remains unclear. In the mouse spinal cord, a population of GABAergic interneurons, GABApre, forms synapses with the terminals of proprioceptive sensory neurons and controls information transfer at sensory-motor connections through presynaptic inhibition. We show that reducing sensory glutamate release results in decreased expression of GABA-synthesizing enzymes GAD65 and GAD67 in GABApre terminals and decreased presynaptic inhibition. Glutamate directs GAD67 expression via the metabotropic glutamate receptor mGluR1beta on GABApre terminals and regulates GAD65 expression via autocrine influence on sensory terminal BDNF. We demonstrate that dual retrograde signals from sensory terminals operate hierarchically to direct the molecular differentiation of GABApre terminals and the efficacy of presynaptic inhibition. These retrograde signals comprise a feedback mechanism by which excitatory sensory activity drives GABAergic inhibition to maintain circuit homeostasis. PMID- 27263973 TI - Anatomical Connections of the Functionally Defined "Face Patches" in the Macaque Monkey. AB - The neural circuits underlying face recognition provide a model for understanding visual object representation, social cognition, and hierarchical information processing. A fundamental piece of information lacking to date is the detailed anatomical connections of the face patches. Here, we injected retrograde tracers into four different face patches (PL, ML, AL, AM) to characterize their anatomical connectivity. We found that the patches are strongly and specifically connected to each other, and individual patches receive inputs from extrastriate cortex, the medial temporal lobe, and three subcortical structures (the pulvinar, claustrum, and amygdala). Inputs from prefrontal cortex were surprisingly weak. Patches were densely interconnected to one another in both feedforward and feedback directions, inconsistent with a serial hierarchy. These results provide the first direct anatomical evidence that the face patches constitute a highly specialized system and suggest that subcortical regions may play a vital role in routing face-related information to subsequent processing stages. PMID- 27263974 TI - The Molecular Motor KIF1A Transports the TrkA Neurotrophin Receptor and Is Essential for Sensory Neuron Survival and Function. AB - KIF1A is a major axonal transport motor protein, but its functional significance remains elusive. Here we show that KIF1A-haploinsufficient mice developed sensory neuropathy. We found progressive loss of TrkA(+) sensory neurons in Kif1a(+/-) dorsal root ganglia (DRGs). Moreover, axonal transport of TrkA was significantly disrupted in Kif1a(+/-) neurons. Live imaging and immunoprecipitation assays revealed that KIF1A bound to TrkA-containing vesicles through the adaptor GTP Rab3, suggesting that TrkA is a cargo of the KIF1A motor. Physiological measurements revealed a weaker capsaicin response in Kif1a(+/-) DRG neurons. Moreover, these neurons were hyposensitive to nerve growth factor, which could explain the reduced neuronal survival and the functional deficiency of the pain receptor TRPV1. Because phosphatidylinositol 3-kinase (PI3K) signaling significantly rescued these phenotypes and also increased Kif1a mRNA, we propose that KIF1A is essential for the survival and function of sensory neurons because of the TrkA transport and its synergistic support of the NGF/TrkA/PI3K signaling pathway. PMID- 27263976 TI - (Hetero)aromatics from dienynes, enediynes and enyne-allenes. AB - The construction of aromatic rings has become a key objective for organic chemists. While several strategies have been developed for the functionalization of pre-formed aromatic rings, the direct construction of an aromatic core starting from polyunsaturated systems is yet a less explored field. The potential of such reactions in the formation of aromatics increased at a regular pace in the last few years. Nowadays, there are reliable and well-established procedures to prepare polyenic derivatives, such as dienynes, enediynes, enyne-allenes and hetero-analogues. This has stimulated their use in the development of innovative cycloaromatizations. Different examples have recently emerged, suggesting large potential of this strategy in the preparation of (hetero)aromatics. Accordingly, this review highlights the recent advancements in this field and describes the different conditions exploited to trigger the process, including thermal and photochemical activation, as well as the use of transition metal catalysis and the addition of electrophiles/nucleophiles or radical species. PMID- 27263977 TI - Carboxylation of terminal alkynes with CO2 using novel silver N-heterocyclic carbene complexes. AB - Four novel N-heterocyclic carbene (NHC) silver complexes, , have been synthesized and characterized. The single X-ray crystal diffraction data indicate a dinuclear solid-state structure for and and a mononuclear structure for and . These complexes have been successfully used as efficient catalysts for the C-H activating carboxylation of terminal alkynes with CO2. A wide range of substrates with various functional groups afforded the corresponding aryl or alkyl substituted propiolic acids in good yields under mild conditions. Moreover, the role of bases and the reaction mechanism is thoroughly discussed. PMID- 27263975 TI - Scribble Scaffolds a Signalosome for Active Forgetting. AB - Forgetting, one part of the brain's memory management system, provides balance to the encoding and consolidation of new information by removing unused or unwanted memories or by suppressing their expression. Recent studies identified the small G protein, Rac1, as a key player in the Drosophila mushroom bodies neurons (MBn) for active forgetting. We subsequently discovered that a few dopaminergic neurons (DAn) that innervate the MBn mediate forgetting. Here we show that Scribble, a scaffolding protein known primarily for its role as a cell polarity determinant, orchestrates the intracellular signaling for normal forgetting. Knocking down scribble expression in either MBn or DAn impairs normal memory loss. Scribble interacts physically and genetically with Rac1, Pak3, and Cofilin within MBn, nucleating a forgetting signalosome that is downstream of dopaminergic inputs that regulate forgetting. These results bind disparate molecular players in active forgetting into a single signaling pathway: Dopamine-> Dopamine Receptor-> Scribble-> Rac-> Cofilin. PMID- 27263978 TI - A belt transect setting strategy for mark-recapture experiments to evaluate the 1D diffusion coefficient of beached litter in the cross-shore direction. AB - We propose a belt transect setting strategy for mark-recapture experiments (MREs) to evaluate the time-independent 1D diffusion coefficient () of marine litter in the cross-shore direction that determines the backwashing flux of the litter, based on two-year MREs for plastic floats (PFs) on Wadahama Beach, Nii jima Island, Japan. When the alongshore width of the belt transect (Lt) was of the order of, or longer than, the length scale of wave-induced nearshore current circulation (Lc), the PFs were rarely transported alongshore across the selected transects prior to being backwashed offshore. Thus, the transect residence time became longer and showed a much weaker dependence on the transect position, in contrast to when Lt was even shorter than Lc. We therefore obtained the diffusion coefficients close to the value of () when we set Lt to the order of, or longer than, Lc. PMID- 27263979 TI - Marine debris: Implications for conservation of rocky reefs in Manabi, Ecuador (Se Pacific Coast). AB - Marine debris (MD) pollution is a problem of global concern because of its impact on marine ecosystems. The current extent of this problem and its implications concerning reef conservation are unknown in Ecuador. The composition and distribution of submerged MD was assessed on two reefs using underwater surveys of geomorphological areas: crest, slope and bottom. MD items were classified according to source and use. Plastic-derived debris represents >90% of total MD found on the reefs, principally composed by plastic containers and nets. 63% of the MD was associated to fishing activities. The composition showed differences between sites and geomorphological areas, monofilament nets were found on the crests, multifilament lines on the slopes and plastic containers on the bottom. MD disposal might be a result of the influx of visitors and fishing activities. Distribution is related to bottom type, level of boating/fishing activity and benthic features. PMID- 27263980 TI - Considerations on the effects of tidal regimes in the movement of floating litter in an estuarine environment: Case study of the estuarine system of Santos-Sao Vicente, Brazil. AB - Floating litter in the estuarine system of Santos-Sao Vicente is common and is part of day-to-day activities of various users of the area. The objective of the present study was to carry out a quali-quantitative evaluation of the occurrence of floating litter, to infer their sources, and to identify environmental factors that are likely to control occurrence and distribution, with particular emphasis on the effects of tidal regimes. Six sampling stations were selected along the aforementioned estuary and visited monthly between July 2010 and January 2012. Floating litter was counted from a fixed sampling station. Plastics prevailed (89.64%) and their main source was domestic activities (55.41%). More litter was found during ebb spring tides, with higher concentrations obeying confluence patterns of the estuary's channels. Results indicated that occurrence can be attributed to the deficiency in basic sewage system in the area and the deliberate disposal into the estuary by the local population. PMID- 27263981 TI - Knowledge about dietary fibre: a fibre study framework. AB - The objective of this work was to study the degree of knowledge about dietary fibre (DF), as influenced by factors such as gender, level of education, living environment or country. For this, a descriptive cross-sectional study was undertaken on a non-probabilistic sample of 6010 participants from 10 countries in different continents (Europe, Africa and America). The results showed that the participants revealed on average a positive but still low global level of knowledge, which alerts for the need to take some actions to further inform the population about DF and its role as a component of a healthy diet. The results also indicated differences between genders, levels of education, living environments and countries. The highest level of knowledge was revealed by the participants from female gender, with higher education and living in urban areas. Concerning the country, the best informed were the participants from Romania, followed by those from Portugal and Turkey while the least informed were from Egypt. PMID- 27263986 TI - Evaluation of the Patient-Reported Outcomes Measurement Information System Upper Extremity Computer Adaptive Test. AB - PURPOSE: The Patient-Reported Outcomes Measurement Information System Upper Extremity Computer Adaptive Test (UE CAT) has recently been made available by the National Institutes of Health to measure physical function outcomes in the upper extremity. We hypothesized that the UE CAT would psychometrically outperform the Disabilities of the Arm, Shoulder, and Hand (DASH) and the Patient-Reported Outcomes Measurement Information System Physical Function Computer Adaptive Test (PF CAT) in a hand patient population. METHODS: The UE CAT, PF CAT, and DASH were each electronically administered to all adult patients who presented to a tertiary hand and upper extremity (nonshoulder) orthopedic clinic. Patient responses were retrospectively studied to determine the validity, reliability, and floor/ceiling effects of all 3 instruments using the Rasch Partial Credit Model. Responder burden and Pearson correlations were calculated for each instrument. RESULTS: A total of 379 patients completed the UE CAT, PF CAT, and the DASH. On average, 6 UE CAT, 9 PF CAT, and 30 DASH questions were administered to each patient. All 3 instruments were each highly correlated with each other. Floor effects were low and similar between all instruments; however, ceiling effects were higher in the UE CAT (10.82%) than in the PF CAT (1.32%) or DASH (5.28%). High person reliability (PR) and item reliability (IR) were found for all 3 metrics: UE CAT (alpha = 0.99; PR = 0.91; IR = 0.94); PF CAT (alpha = 0.95; PR = 0.89; IR = 0.96); and DASH (alpha = 0.97; PR = 0.95; IR = 0.99). The UE CAT questions had the best item-fit: only 1 of 15 UE CAT items had poor fit in contrast to 4 of 30 DASH items and 7 of 33 PF CAT items. CONCLUSIONS: The psychometric properties of the UE CAT compare favorably with the PF CAT and the DASH in nonshoulder upper extremity patients. The relatively large ceiling effect found in the UE CAT could be improved with item bank expansion to include items at the upper end of function. CLINICAL RELEVANCE: The UE CAT is a useful patient reported outcome measure that merits further investigation. PMID- 27263987 TI - Semiautomated Ventilation Defect Quantification in Exercise-induced Bronchoconstriction Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: A Repeatability Study. AB - RATIONALE AND OBJECTIVES: This study aimed to compare the performance of a semiautomated ventilation defect segmentation approach, adaptive K-means, with manual segmentation of hyperpolarized helium-3 magnetic resonance imaging in subjects with exercise-induced bronchoconstriction (EIB). MATERIALS AND METHODS: Six subjects with EIB underwent hyperpolarized helium-3 magnetic resonance imaging and spirometry tests at baseline, post exercise, and recovery over two separate visits. Ventilation defects were analyzed by two methods. First, two independent readers manually segmented ventilation defects. Second, defects were quantified by an adaptive K-means method that corrected for coil sensitivity, applied a vesselness filter to estimate pulmonary vasculature, and segmented defects adaptively based on the overall low-intensity signals in the lungs. These two methods were then compared in four aspects: (1) ventilation defect percent (VDP) measurements, (2) correlation between spirometric measures and measured VDP, (3) regional VDP variations pre- and post exercise challenge, and (4) Dice coefficient for spatial agreement. RESULTS: The adaptive K-means method was ~5 times faster, and the measured VDP bias was under 2%. The correlation between predicted forced expiratory volume in 1 second over forced vital capacity and VDP measured by adaptive K-means (rho = -0.64, P <0.0001) and by the manual method (rho = -0.63, P <0.0001) yielded almost identical 95% confidence intervals. Neither method of measuring VDP indicated apical/basal or anterior dependence in this small study cohort. CONCLUSIONS: Compared to the manual method, the adaptive K-means method provided faster, reproducible, comparable measures of VDP in EIB and may be applied to a variety of lung diseases. PMID- 27263988 TI - Tuning of the electronic and photophysical properties of ladder-type quaterphenyl by selective methylene-bridge fluorination. AB - The photophysics (spectral positions, band shapes, fluorescence quantum yields and lifetimes) of a series of fluorinated ladder type quaterphenyls L4P and L4P Fn (n = 2, 4, 6) depend strongly on the degree and position of fluorine, despite the fact that substitution is not performed in the rings but only in methylene bridges. This is driven by subtle differences in the molecular orbitals (MOs) participating in the electronic transitions, and in the vibronic pattern of the S0 and S1 electronic states as revealed by (TD)DFT calculations. Solid state spectra for n = 0, 2, 4 are similar to those of solution due to small intermolecular interactions as revealed by combined X-ray and (TD)DFT analysis. PMID- 27263989 TI - Phenological mismatch and ontogenetic diet shifts interactively affect offspring condition in a passerine. AB - Climate change may cause phenological asynchrony between trophic levels, which can lead to mismatched reproduction in animals. Although indirect effects of mismatch on fitness are well described, direct effects on parental prey choice are not. Moreover, direct effects of prey variation on offspring condition throughout their early development are understudied. Here, we used camera trap data collected over 2 years to study the effects of trophic mismatch and nestling age on prey choice in pied flycatchers (Ficedula hypoleuca). Furthermore, we studied the effect of mismatch and variation in nestling diet on offspring condition. Both experimentally induced and natural mismatches with the caterpillar peak negatively affected absolute and relative numbers of caterpillars and offspring condition (mass, tarsus and wing length) and positively affected absolute and relative numbers of flying insects in the nestling diet. Feeding more flying insects was negatively correlated with nestling day 12 mass. Both descriptive and experimental data showed preferential feeding of spiders when nestlings were <7 days old. Receiving more spiders during this phase was positively correlated with tarsus growth. These results highlight the need for a more inclusive framework to study phenological mismatch in nature. The general focus on only one prey type, the rarity of studies that measure environmental abundance of prey, and the lack of timing experiments in dietary studies currently hamper understanding of the actual trophic interactions that affect fitness under climate change. PMID- 27263990 TI - Pediatric Sickle Cell Disease and Parent and Child Catastrophizing. AB - Pain catastrophizing is poorly understood in children and adolescents with sickle cell disease (SCD) and their parents. The objectives of this study were twofold: 1) to evaluate the interplay between parent and child pain catastrophizing and its effect on disability among youth with SCD, and 2) to evaluate whether child pain catastrophizing served as a mechanism that explained the relation between pain and functional disability within the context of varying levels of parent pain catastrophizing. One hundred youth (8-18 years old) with SCD and parents completed measures of pain characteristics (pain frequency and intensity), catastrophizing (Pain Catastrophizing Scale), and the outcome of functional disability (Functional Disability Inventory) in a cross-sectional study. Youth with low levels of catastrophizing showed high levels of disability in the presence of high levels of parent catastrophizing. Additionally, child pain catastrophizing was a significant mechanism that partially explained the effect of higher pain frequency and pain intensity on greater levels of disability, but only at low levels of parent pain catastrophizing. High levels of parent catastrophizing and incongruence between child and parent catastrophizing contributes to poorer functional outcomes in youth with SCD. PERSPECTIVE: Youth with SCD and parents with high levels of catastrophic thinking about child pain or incongruent levels of catastrophizing are at increased risk for greater child disability. Clinicians treating youth with SCD should focus on targeting worried thinking about pain in patients and parents to facilitate improved function. PMID- 27263991 TI - Negative Interpretation Bias and the Experience of Pain in Adolescents. AB - Negative interpretation bias, the tendency to appraise ambiguous situations in a negative or threatening way, has been suggested to be important for the development of adult chronic pain. To our knowledge, this is the first study to examine the role of a negative interpretation bias in adolescent pain. We first developed and piloted a novel task that measures the tendency for adolescents to interpret ambiguous situations as indicative of pain and bodily threat. Using this task in a separate community sample of adolescents (N = 115), we then found that adolescents who catastrophize about pain, as well as those who reported more pain issues in the preceding 3 months, were more likely to endorse negative interpretations, and less likely to endorse benign interpretations, of ambiguous situations. This interpretation pattern was not, however, specific for situations regarding pain and bodily threat, but generalized across social situations as well. We also found that a negative interpretation bias, specifically in ambiguous situations that could indicate pain and bodily threat, mediated the association between pain catastrophizing and recent pain experiences. Findings may support one potential cognitive mechanism explaining why adolescents who catastrophize about pain often report more pain. PERSPECTIVE: This article presents a new adolescent measure of interpretation bias. We found that the tendency to interpret ambiguous situations as indicative of pain and bodily threat may be one potential cognitive mechanism explaining why adolescents who catastrophize about pain report more pain, thus indicating a potential novel intervention target. PMID- 27263992 TI - Relations Between Brain Alterations and Clinical Pain Measures in Chronic Musculoskeletal Pain: A Systematic Review. AB - Compelling evidence has shown chronic widespread and exaggerated pain experience in chronic musculoskeletal pain (MSKP) conditions. In addition, neuroimaging research has revealed morphological and functional brain alterations in these patients. It is hypothesized that brain alterations play a role in the persistent pain complaints of patients with chronic MSKP. Nevertheless, lack of overview exists regarding the relations between brain alterations and clinical measures of pain. The present systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, to investigate the relations between structural or functional brain alterations, using magnetic resonance imaging scans, and clinical pain measures in patients with chronic MSKP. PubMed, Web of Science, Cinahl, and Cochrane databases were searched. First, the obtained articles were screened according to title and abstract. Second, the screening was on the basis of full-text. Risk of bias in included studies was investigated according to the modified Newcastle-Ottawa Scale. Twenty studies met the inclusion criteria. Moderate evidence shows that higher pain intensity and pressure pain sensitivity are related to decreased regional gray matter (GM) volume in brain regions encompassing the cingulate cortex, the insula, and the superior frontal and temporal gyrus. Further, some evidence exists that longer disease duration in fibromyalgia is correlated with decreased total GM volume. Yet, inconclusive evidence exists regarding the association of longer disease duration with decreased or increased regional GM volume in other chronic MSKP conditions. Inconclusive evidence was found regarding the direction of the relation of pain intensity and pressure pain sensitivity with microstructural white matter and functional connectivity alterations. In conclusion, preliminary to moderate evidence demonstrates relations between clinical pain measures, and structural and functional connectivity alterations within brain regions involved in somatosensory, affective, and cognitive processing of pain in chronic MSKP. Nevertheless, inconclusive results exist regarding the direction of these relations. Further research is warranted to unravel whether these brain alterations are positively or negatively correlated to clinical pain measures. PERSPECTIVE: Structural and functional brain alterations within regions involved in somatosensory, affective, and cognitive pain processing play a crucial role in the persistent pain of chronic MSKP patients. Accordingly, these brain alterations have to be taken into account when assessing and treating patients with chronic MSKP. PMID- 27263993 TI - Corrigendum to "The persistent influence of concussion on attention, executive control and neuroelectric function in preadolescent children" [Int. J. Psychophysiol. 99C (2016) 85-95]. PMID- 27263994 TI - Measurement of bound and pore water T1 relaxation times in cortical bone using three-dimensional ultrashort echo time cones sequences. AB - PURPOSE: We present three-dimensional ultrashort echo time Cones (3D UTE Cones) techniques for quantification of total water T1 ( T1TW), bound water T1 ( T1BW), and pore water T1 ( T1PW) in vitro and in vivo using a 3 Tesla (T) scanner. METHODS: T1TW, T1BW, and T1PW were measured with three-dimensional (3D) Cones and adiabatic inversion recovery Cone (IR-Cone) sequences. Two-dimensional (2D) nonselective ultrashort echo time (UTE) techniques, including saturation recovery, variable repetition times (TRs), and inversion recovery (IR) preparation approaches were compared with 3D-Cones techniques on bovine cortical bone samples (n = 8). The 3D Cones sequences were used to measure T1TW, T1BW, and T1PW in the tibial midshaft of healthy volunteers (n = 8). RESULTS: Comparable T1 images were achieved for cortical bone between 3D Cones and 2D UTE techniques as well as those published in the literature. The 3D Cones sequences showed a mean T1TW of 208 +/- 22 ms, a mean T1PW of 545 +/- 28 ms, and a mean T1BW of 131 +/- 12 ms for bovine cortical bone; and a mean T1TW of 246 +/- 32 ms, a mean T1PW of 524 +/- 46 ms, and a mean T1BW of 134 +/- 11 ms for the tibial midshaft of healthy volunteers. CONCLUSIONS: The 3D Cones sequences can be used for fast volumetric assessment of bound and pore water T1 images in vitro and in vivo. Magn Reson Med 77:2136-2145, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27263995 TI - Trends in hospitalizations of pregnant HIV-infected women in the United States: 2004 through 2011. AB - BACKGROUND: With the development and widespread use of combination antiretroviral therapy, HIV-infected women live longer, healthier lives. Previous research has shown that, since the adoption of combination antiretroviral therapy in the United States, rates of morbidity and adverse obstetric outcomes remained higher for HIV-infected pregnant women compared with HIV-uninfected pregnant women. Monitoring trends in the outcomes these women experience is essential, as recommendations for this special population continue to evolve with the progress of HIV treatment and prevention options. OBJECTIVE: We conducted an analysis comparing rates of hospitalizations and associated outcomes among HIV-infected and HIV-uninfected pregnant women in the United States from 2004 through 2011. STUDY DESIGN: We used cross-sectional hospital discharge data for girls and women age 15-49 from the 2004, 2007, and 2011 Nationwide Inpatient Sample, a nationally representative sample of US hospital discharges. Demographic characteristics, morbidity outcomes, and time trends were compared using chi(2) tests and multivariate logistic regression. Analyses were weighted to produce national estimates. RESULTS: In 2011, there were 4751 estimated pregnancy hospitalizations and 3855 delivery hospitalizations for HIV-infected pregnant women; neither increased since 2004. Compared with those of HIV-uninfected women, pregnancy hospitalizations of HIV-infected women were more likely to be longer, be in the South and Northeast, be covered by public insurance, and incur higher charges (all P < .005). Hospitalizations among pregnant women with HIV infection had higher rates for many adverse outcomes. Compared to 2004, hospitalizations of HIV infected pregnant women in 2011 had higher odds of gestational diabetes (adjusted odds ratio, 1.81; 95% confidence interval, 1.16-2.84), preeclampsia/hypertensive disorders of pregnancy (adjusted odds ratio, 1.58; 95% confidence interval, 1.12 2.24), viral/mycotic/parasitic infections (adjusted odds ratio, 1.90; 95% confidence interval, 1.69-2.14), and bacterial infections (adjusted odds ratio, 2.54; 95% confidence interval, 1.53-4.20). Bacterial infections did not increase among hospitalizations of HIV-uninfected pregnant women. CONCLUSION: The numbers of hospitalizations during pregnancy and delivery have not increased for HIV infected women since 2004, a departure from previously estimated trends. Pregnancy hospitalizations of HIV-infected women remain more medically complex than those of HIV-uninfected women. An increasing trend in infections among the delivery hospitalizations of HIV-infected pregnant women warrant further attention. PMID- 27263996 TI - Pregnancy as a window to future health: maternal placental syndromes and short term cardiovascular outcomes. AB - BACKGROUND: Cardiovascular disease is the leading cause of death among women. Identifying risk factors for future cardiovascular disease may lead to earlier lifestyle modifications and disease prevention. Additionally, interpregnancy development of cardiovascular disease can lead to increased perinatal morbidity in subsequent pregnancies. Identification and implementation of interventions in the short term (within 5 years of first pregnancy) may decrease morbidity in subsequent pregnancies. OBJECTIVE: We identified the short-term risk (within 5 years of first pregnancy) of cardiovascular disease among women who experienced a maternal placental syndrome, as well as preterm birth and/or delivered a small for-gestational-age infant. STUDY DESIGN: We conducted a retrospective cohort study using a population-based, clinically enhanced database of women in the state of Florida. Nulliparous women and girls aged 15-49 years experiencing their first delivery during the study time period with no prepregnancy history of diabetes mellitus, hypertension, or heart or renal disease were included in the study. The risk of subsequent cardiovascular disease was compared among women who did and did not experience a placental syndrome during their first pregnancy. Risk was then reassessed among women with placental syndrome and preterm birth or delivering a small-for-gestational-age infant vs those without these adverse pregnancy outcomes. RESULTS: The final study population was 302,686 women and girls. Median follow-up time for each patient was 4.9 years. The unadjusted rate of subsequent cardiovascular disease among women and girls with any placental syndrome (11.8 per 1000 women) was 39% higher than the rate among women and girls without a placental syndrome (8.5 per 1000 women). Even after adjusting for sociodemographic factors, preexisting conditions, and clinical and behavioral conditions associated with the current pregnancy, women and girls with any placental syndrome experienced a 19% increased risk of cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.07-1.32). Women and girls with >1 placental syndrome had the highest cardiovascular disease risk (hazard ratio, 1.43; 95% confidence interval, 1.20-1.70), followed by those with eclampsia/preeclampsia alone (hazard ratio, 1.42; 95% confidence interval, 1.14 1.76). When placental syndrome was combined with preterm birth and/or small for gestational age, the adjusted risk of cardiovascular disease increased 45% (95% confidence interval, 1.24-1.71). Women and girls with placental syndrome who then developed cardiovascular disease experienced a 5-fold increase in health care related costs during follow-up, compared to those who did not develop cardiovascular disease. CONCLUSION: Women and girls experiencing placental syndromes and preterm birth or small-for-gestational-age infant are at increased risk of subsequent cardiovascular disease in short-term follow-up. Strategies to identify and improve cardiovascular disease risk in the postpartum period may improve future heart disease outcomes. PMID- 27263997 TI - Impact on family and parental stress of prenatal vs postnatal repair of myelomeningocele. AB - BACKGROUND: The Management of Myelomeningocele Study was a multicenter, randomized controlled trial that compared prenatal repair with standard postnatal repair for fetal myelomeningocele. OBJECTIVE: We sought to describe the long-term impact on the families of the women who participated and to evaluate how the timing of repair influenced the impact on families and parental stress. STUDY DESIGN: Randomized women completed the 24-item Impact on Family Scale and the 36 item Parenting Stress Index Short Form at 12 and 30 months after delivery. A revised 15-item Impact on Family Scale describing overall impact was also computed. Higher scores reflected more negative impacts or greater stress. In addition, we examined Family Support Scale and Family Resource Scale scores along with various neonatal outcomes. Repeated measures analysis was conducted for each scale and subscale. RESULTS: Of 183 women randomized, 171 women completed the Impact on Family Scale and 172 completed the Parenting Stress Index at both 12 and 30 months. The prenatal surgery group had significantly lower revised 15-item Impact on Family Scale scores as well as familial-social impact subscale scores compared to the postnatal surgery group (P = .02 and .004, respectively). There was no difference in total parental stress between the 2 groups (P = .89) or in any of the Parenting Stress Index Short Form subscales. In addition, walking independently at 30 months and family resources at 12 months were associated with both family impact and parental stress. CONCLUSION: The overall negative family impact of caring for a child with spina bifida, up to 30 months of age, was significantly lower in the prenatal surgery group compared to the postnatal surgery group. Ambulation status and family resources were predictive of impact on family and parental stress. PMID- 27263998 TI - Marijuana use and its effects in pregnancy. AB - BACKGROUND: It is generally assumed that marijuana is one of the more widely used controlled substances during pregnancy. However, there remains a general paucity of population-based data regarding its use and subsequent perinatal morbidity. We hypothesized that direct patient query during pregnancy regarding marijuana, tobacco, and nicotine use would provide crucial initial population-based data on perinatal risk. OBJECTIVE: Our study sought to examine maternal and neonatal outcomes in pregnancies with reported marijuana exposure, in isolation or in combination with maternal cigarette smoking. STUDY DESIGN: We applied a retrospective cohort study design to subjects (n = 12,069) with available information on marijuana use and pregnancy outcomes. Since 2011, we have routinely and directly questioned all gravidae regarding use of marijuana, tobacco, and nicotine-containing products. We examined perinatal outcomes in marijuana smokers vs nonsmokers, as well as patients reporting both marijuana and cigarette smoking. Multivariate analysis enabled determination of adjusted odds ratios for maternal and fetal outcomes, adjusting for confounders. Significance was determined with Mann-Whitney U, chi(2), and Fischer exact tests (as appropriate). RESULTS: In all, 106/12,069 reported marijuana use (0.88%), with 48/12,069 (0.4%; or 48/106, 45%) concurrently using cigarettes and marijuana. After controlling for potential confounding variables, while marijuana use alone was not associated with significant adverse outcomes, use in combination with cigarette smoking was significantly associated with increased risk of multiple adverse perinatal outcomes (increased occurrence of maternal asthma [adjusted odds ratio, 2.4; 95% confidence interval, 1.0-5.9]; preterm birth [adjusted odds ratio, 2.6; 95% confidence interval, 1.3-4.9]; decreased [<25th percentile] head circumference [adjusted odds ratio, 2.8; 95% confidence interval, 1.3-4.3]; and decreased [<25th percentile] birthweight [adjusted odds ratio, 2.8; 95% confidence interval, 1.6-5.0]). Maternal pregnancy-related hypertension was not increased in marijuana smokers (adjusted odds ratio, 1.30; 95% confidence interval, 0.681-2.498), or in cigarette smokers (adjusted odds ratio, 1.4; 95%, confidence interval, 0.9-1.9). However, co-users had elevated rates of preeclampsia compared to nonusers (adjusted odds ratio, 2.5; 95% confidence interval, 1.4-5.0). CONCLUSION: In our initial cohort analysis, after controlling for potential confounders, while marijuana exposure alone was not associated with significant perinatal adverse outcomes, co-use with cigarette smoking rendered increased risk over either alone. Due to observed prevalence of concurrent cigarette and marijuana use, it is of likely importance to counsel patients regarding use in pregnancy. PMID- 27264000 TI - Role of IgE in autoimmunity. AB - There is accumulating evidence to suggest that IgE plays a significant role in autoimmunity. The presence of circulating self-reactive IgE in patients with autoimmune disorders has been long known but, at the same time, largely understudied. However, studies have shown that the increased IgE concentration is not associated with higher prevalence for atopy and allergy in patients with autoimmune diseases, such as systemic lupus erythematosus. IgE-mediated mechanisms are conventionally known to facilitate degranulation of mast cells and basophils and promote TH2 immunity, mechanisms that are not only central to mounting an appropriate defense against parasitic worms, noxious substances, toxins, venoms, and environmental irritants but that also trigger exuberant allergic reactions in patients with allergies. More recently, IgE autoantibodies have been recognized to participate in the self-inflicted damaging immune responses that characterize autoimmunity. Such autoimmune responses include direct damage on tissue-containing autoantigens, activation and migration of basophils to lymph nodes, and, as observed most recently, induction of type 1 interferon responses from plasmacytoid dendritic cells. The importance of IgE as a central pathogenic mechanism in autoimmunity has now been clinically validated by the approval of omalizumab, an anti-IgE mAb, for patients with chronic spontaneous urticaria and for the clinical benefit of patients with bullous pemphigoid. In this review we summarize recent reports describing the prevalence of self-reactive IgE and discuss novel findings that incriminate IgE as central in the pathogenesis of inflammatory autoimmune disorders. PMID- 27263999 TI - Fifty years later: Emerging functions of IgE antibodies in host defense, immune regulation, and allergic diseases. AB - Fifty years ago, after a long search, IgE emerged as the circulating factor responsible for triggering allergic reactions. Its extremely low concentration in plasma created significant hurdles for scientists working to reveal its identity. We now know that IgE levels are invariably increased in patients affected by atopic conditions and that IgE provides the critical link between the antigen recognition role of the adaptive immune system and the effector functions of mast cells and basophils at mucosal and cutaneous sites of environmental exposure. This review discusses the established mechanisms of action of IgE in pathologic immediate hypersensitivity, as well as its multifaceted roles in protective immunity, control of mast cell homeostasis, and its more recently revealed immunomodulatory functions. PMID- 27264002 TI - The discovery of IgE. AB - In 1919, the search began for the factor, later called reagin, that could mediate an allergy, such as allergic asthma, in sera of allergic subjects. In 1967, the fifth class of immunoglobulins, IgE, was discovered and found to be able to carry reagin activity. This discovery has had immense importance for the understanding, diagnosis, and treatment of allergic diseases. PMID- 27264004 TI - Correction. PMID- 27264001 TI - IgE in the diagnosis and treatment of allergic disease. AB - Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the "allergic" disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow's milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose alpha-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response. PMID- 27264005 TI - Dynamics of Molecular Crystals by Means of (1) H NMR Relaxometry: Dynamical Heterogeneity versus Homogenous Motion. AB - (1) H NMR relaxometry was used to reveal information on the dynamical properties of the molecular crystal (PyH)5 Bi2 Br11 (PyH=C5 H6 N, pyridinium cation), chosen as an example of a solid that exhibits a complex structure and rotational-like dynamics. Experimental studies were performed over a very broad frequency range, from 4 kHz to 40 MHz (referring to the (1) H resonance frequency) versus temperature. The extensive set of data was thoroughly analyzed in terms of two motional models differing with respect to the assumed mechanism (heterogeneous versus homogenous) of the motion of the PyH cations. A Cole-Davidson distribution of the correlation times describing the assumed motional heterogeneity was tested against a concept of two correlation times characterizing the rotation-like dynamics of the PyH cation around the perpendicular axes differing by about one order of magnitude. The parameters describing the dynamics of the cation, obtained by means of both models, were compared and discussed. PMID- 27264008 TI - Supply, capacity, and demand. PMID- 27264006 TI - Prognostic impact of bone marrow fibrosis in primary myelofibrosis. A study of the AGIMM group on 490 patients. AB - The prognostic significance of bone marrow (BM) fibrosis grade in patients with primary myelofibrosis (PMF) is still debated. A fibrosis grade greater than 1 was shown to associate with higher risk of death, and addition of fibrosis grade to IPSS score resulted in a more accurate prediction of survival. The aim of this study was to analyze the prognostic impact of BM fibrosis in 490 patients with PMF, evaluated at diagnosis, molecularly annotated and with extensive follow-up information. We found that fibrosis grade 2 and greater on a 0-3 scale was associated with clinical characteristics indicative of a more advanced disease, such as anemia, leukopenia, thrombocytopenia, constitutional symptoms, larger splenomegaly and a higher IPSS risk category. Patients with higher grade of fibrosis were also more likely to have additional somatic mutations in ASXL1 and EZH2, that are prognostically adverse. Median survival was significantly reduced in patients with grade 2 and 3 fibrosis as compared with grade 1; this effect was maintained when analysis was restricted to younger patients. In multivariate analysis, fibrosis grade independently predicted for survival regardless of IPSS variables and mutational status; the adverse impact of fibrosis was noticeable especially in lower IPSS risk categories. Overall, results indicate that higher grades of fibrosis correlate with unique clinical and molecular aspects and represent an independent adverse variable in patients with PMF; these observations deserve confirmation in prospectively designed series of patients. Am. J. Hematol. 91:918-922, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27264007 TI - A modified varying-stage adaptive phase II/III clinical trial design. AB - Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27264009 TI - Primum non confundere: whole blood versus apheresis platelet debate continues. PMID- 27264010 TI - Central retinal vein occlusion after plateletpheresis. PMID- 27264012 TI - Bleeding disorders identified in blood donors after quality control of fresh frozen plasma. PMID- 27264013 TI - Enhancing platelet transfusion safety: not a one-size-fits-all approach. PMID- 27264014 TI - Highlighting oft-overlooked granulocyte-colony-stimulating factor kinetics. PMID- 27264015 TI - ICBS ABSTRACTS. PMID- 27264016 TI - Unexpectedly high bacteriochlorophyll a concentrations in neotropical tank bromeliads. AB - The contribution of bacteriochlorophyll a (BChl a) to photosynthetically driven electron transport is generally low in aquatic and terrestrial systems. Here, we provide evidence that anoxygenic bacterial phototrophy is widespread and substantial in water retained by tank bromeliads of a primary rainforest in French Guiana. An analysis of the water extracted from 104 randomly selected tank bromeliads using infrared fluorimetry suggested the overall presence of abundant anoxygenic phototrophic bacterial populations. We found that purple bacteria dominated these populations responsible for unusually high BChl a/chlorophyll a ratios (>50%). Our data suggest that BChl a-based phototrophy in tank bromeliads can have significant effects on the ecology of tank-bromeliad ecosystems and on the carbon and energy fluxes in Neotropical forests. PMID- 27264017 TI - Neoadjuvant treatment sequencing adds value to the care of patients with operable pancreatic cancer. AB - Treatment sequencing for resectable pancreatic cancer remains controversial and there is lack of level one evidence comparing neoadjuvant versus adjuvant strategies. However, a comparison of the cost-effectiveness analysis of the treatment strategies may help to better define the healthcare value of each approach. This review will highlight the rationale for multimodality therapy in the treatment of pancreatic cancer, discuss the advantages and disadvantages of adjuvant therapy, and conceptualize the cost-effectiveness of a neoadjuvant approach with regard to healthcare value. J. Surg. Oncol. 2016;114:291-295. (c) 2016 Wiley Periodicals, Inc. PMID- 27264018 TI - Use of nutritional supplements by Danish elite athletes and fitness customers. AB - The nutritional supplement (NS) industry is one of the fastest growing in the world, and NS use in Denmark is among the highest in Europe. However, the exact use in elite athletes and fitness customers targeted for doping control is unknown. Information from 634 doping control forms obtained in 2014 was evaluated (elite athletes: n = 361; fitness customers: n = 273). The majority of female (92.6%) and male (85.0%) elite athletes and female (100.0%) and male (94.0%) fitness customers declared using one or more NS. The use of non-ergogenic NS was more prevalent in women than in men and in younger (15-34 years) compared with older (35-49 years) subjects, but it was less prevalent in intermittent compared with endurance and power/strength sports. Additionally, fitness customers who tested positive for doping also reported using more NS than subjects testing negative, indicating an association between NS and doping abuse. The present results demonstrate a very high prevalence of NS usage in both elite athletes and fitness customers. This highlights the importance of a strong national regulation of NS to avoid contamination of NS with doping substances. PMID- 27264019 TI - HIV1-viral protein R (Vpr) mutations: associated phenotypes and relevance for clinical pathologies. AB - Over the last 30 years, research into HIV has advanced the knowledge of virus genetics and the development of efficient therapeutic strategies. HIV-1 viral protein R (Vpr) is a specialized and multifunctional protein that plays important roles at multiple stages of the HIV-1 viral life cycle. This protein interacts with a number of cellular and viral proteins and with multiple activities including nuclear transport of the pre-integration complex (PIC) to the nucleus, transcriptional activation, cell cycle arrest at G2/M transition phase and induction of cell death via apoptosis. Specifically, Vpr has been shown to control many host cell functions through a variety of biological processes and by interaction with several cellular pathways. The different functions of Vpr may enhance viral replication and impair the immune system in HIV-1 infected patients. Importantly, functional defects induced by mutations in the Vpr protein correlate with slow disease progression of HIV-infected patients. Vpr is also associated with other concomitant pathologies developed by these patients, which may lead it to be considered as a potential novel therapeutic target. This review will focus on HIV-1 Vpr, mainly on the importance of its structural mutations on the progression of HIV infection, associated phenotypes and relevance for clinical pathologies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27264021 TI - Blastic plasmacytoid dendritic cell neoplasm: diagnostic criteria and therapeutical approaches. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematological malignancy derived from the precursors of plamacytoid dendritic cells, with an aggressive clinical course and high frequency of cutaneous and bone marrow involvement. Neoplastic cells express CD4, CD43 (also termed SPN), CD45RA and CD56 (also termed NCAM1), as well as the plasmacytoid dendritic cell-associated antigens CD123 (also termed IL3RA), BDCA-2 (also termed CD303, CLEC4E) TCL1 and CTLA1 (also termed GZMB). The median survival is only a few months as the tumour exhibits a progressive course despite initial response to chemotherapy. The best modality of treatment remains to be defined. Generally, patients receive acute leukaemia-like induction, according to acute myeloid leukaemia (AML)-type or acute lymphoid leukaemia (ALL)-type regimens. The frequent neuromeningeal involvement indicates systematic pre-emptive intrathecal chemotherapy in addition to intensive chemotherapy. Allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed in first remission, may improve the survival. Preliminary data suggest a potential role for immunomodulatory agents and novel targeted drugs. Herein epidemiology, clinical manifestations, diagnosis and management of BPDCN will be presented. In detail, this review focuses on the therapeutic aspects of BPDCN, proposing a treatment algorithm for the management of the disease, including induction chemotherapy, allogeneic HSCT and intrathecal prophylaxis at different steps of treatment, according to compliance, biological and clinical characteristics of patients. PMID- 27264020 TI - Marital status and survival in patients with gastric cancer. AB - The objective of this study is to examine the impact of marital status on incidence of metastasis at diagnosis, receipt of surgery, and cause-specific survival (CSS) in patients with gastric cancer (GC). Research data is extracted from The Surveillance, Epidemiology, and End Results (SEER) database, and 18,196 patients diagnosed with GC from 2004 to 2010 are involved. Effects of marital status on incidence of metastasis at diagnosis, receipt of surgery, and CSS are determined using multivariable logistic regression and multivariable Cox regression models, as appropriate. Single GC patients have a higher incidence of metastasis at diagnosis than married patients, while the differences between divorced/separated patients or widowed patients and married patients are not significant. Among those without distant metastasis, single patients, divorced/separated patients, and widowed patients are much less likely to accept surgery compared with married patients. Finally, in the whole group of 18,196 GC patients, single patients, divorced/separated patients, and widowed patients have shorter CSS compared with married patients, even in each of the TNM stage. Marriage had a protective effect against undertreatment and cause-specific mortality (CSM) in GC. Spousal support may contribute to higher rate of surgery receipt and better survival in patients with GC. PMID- 27264022 TI - Oxytocin is needed, but it is no magic bullet. PMID- 27264023 TI - Comments on 'Test non-inferiority (and equivalence) based on the odds ratio under a simple crossover trial'. PMID- 27264024 TI - The transplant team's support of kidney transplant recipients to take their prescribed medications: a collective responsibility. AB - AIMS AND OBJECTIVES: To obtain an understanding of how health professionals support the kidney transplant patient to take their medications as prescribed long term. BACKGROUND: Kidney transplantation requires stringent adherence to complex medication regimens to prevent graft rejection and to maintain general well-being. Medication nonadherence is common in kidney transplantation, emerging in the first few months post-transplantation, leading to poor patient outcomes. DESIGN: Exploratory qualitative design. METHODS: Five focus groups were conducted with a total of seven renal nurse transplant coordinators, two renal transplant nurse unit managers, seven nephrologists, seven pharmacists, four social workers, and one consumer representative representing all five hospitals offering adult kidney transplantation in Victoria, Australia in 2014. The views of two general practitioners who were unable to attend the focus groups were incorporated into the data set. All data underwent thematic analysis. RESULTS: Analysis revealed that adherence was a collective responsibility involving the whole of the transplant team and the patient via education blitz in hospital, identifying and managing nonadherence, promotion of self-advocacy, and the partnership between the patient and health professional. Patients were directed how to take their complex medications to be self-empowered, yet the partnership between the patient and health professional limited the patient's voice. CONCLUSION: Although medication adherence was a collective responsibility, communication was often one way chiefly as a result of staffing and time constraints, hindering effective partnerships necessary for medication adherence. Expert skills in communication and adherence counselling are necessary to identify barriers affecting medication adherence. Patients need to be systematically screened, prepared and supported long-term within an accommodating healthcare system for the reality of caring for their transplanted kidney. RELEVANCE TO CLINICAL PRACTICE: Kidney transplant recipients require systematic preparation and quality long-term follow-up to adhere to their prescribed medications. PMID- 27264025 TI - Symmetry breaking in ligand-protected gold clusters probed by nonlinear optics. AB - The first hyperpolarizabilities of [Au25(SR)18](-1/0) and Au38(SR)24 clusters were determined by Hyper-Rayleigh Scattering. A strong dependence on the molecular symmetry was observed, and we explore two strategies to destroy the center of inversion in [Au25(SR)18](-1/0), protection by chiral ligands and alloying of the cluster with silver. This may open new avenues to applications of Au : SR clusters in second-order nonlinear optics. PMID- 27264026 TI - Amylin modulates the formalin-induced tonic pain behaviours in rats. AB - BACKGROUND: Amylin is a peptide from the calcitonin gene-related peptides (CGRP) family that is expressed by nociceptors. Amylin may modulate pain via a spinal action. METHODS: The effect of amylin's administration on the formalin test of acute and tonic pain was evaluated. Amylin's ability to modulate neuronal activity was analysed by c-Fos expression at the spinal cord lumbar 4-5 region (L4-5) and brain. RESULTS: Amylin subcutaneous administration 20 min prior, but not immediately before formalin, shortened the interphase and anticipated the beginning of the tonic pain phase. Amylin reduced the number of activated spinal cord neurons. Blockade of spinal amylin-receptors by prior L4-5 intrathecal administration of an amylin-receptor antagonist (AC187) attenuated these effects, whereas intrathecal BIBN4096 (CGRP-receptor antagonist) did not, proving that part of amylin's effects were spinally mediated via amylin-receptors. The locus coeruleus and other areas involved in descending modulation and affective responses to pain showed an increased number of activated neurons upon amylin subcutaneous administration, suggesting a role for supraspinal areas in some observed effects. L4-5 intrathecal injection of amylin or AC187 showed that both ligands attenuated tonic pain, but blockade of the amylin-receptor action by AC187 decreased further the number of paw jerks in this period. CONCLUSIONS: Overall, data suggested that amylin modulates pain with an inflammatory component and the autoanalgesic/inhibitory mechanisms occurring in the interphase of the formalin test. Amylin might have affected the nociceptive system at different levels (spinal cord and brain), explaining the different effects observed according to the time of amylin injection. WHAT DOES THIS STUDY ADD?: Amylin modulated formalin interphase and tonic pain behaviours probably by targeting spinal neurons and affecting supraspinal areas involved in affective and modulatory components of pain. Activation of spinal amylin-receptors may contribute to the initiation of inflammatory pain mechanisms. PMID- 27264027 TI - Habitual wearers of colored lenses adapt more rapidly to the color changes the lenses produce. AB - The visual system continuously adapts to the environment, allowing it to perform optimally in a changing visual world. One large change occurs every time one takes off or puts on a pair of spectacles. It would be advantageous for the visual system to learn to adapt particularly rapidly to such large, commonly occurring events, but whether it can do so remains unknown. Here, we tested whether people who routinely wear spectacles with colored lenses increase how rapidly they adapt to the color shifts their lenses produce. Adaptation to a global color shift causes the appearance of a test color to change. We measured changes in the color that appeared "unique yellow", that is neither reddish nor greenish, as subjects donned and removed their spectacles. Nine habitual wearers and nine age-matched control subjects judged the color of a small monochromatic test light presented with a large, uniform, whitish surround every 5s. Red lenses shifted unique yellow to more reddish colors (longer wavelengths), and greenish lenses shifted it to more greenish colors (shorter wavelengths), consistent with adaptation "normalizing" the appearance of the world. In controls, the time course of this adaptation contained a large, rapid component and a smaller gradual one, in agreement with prior results. Critically, in habitual wearers the rapid component was significantly larger, and the gradual component significantly smaller than in controls. The total amount of adaptation was also larger in habitual wearers than in controls. These data suggest strongly that the visual system adapts with increasing rapidity and strength as environments are encountered repeatedly over time. An additional unexpected finding was that baseline unique yellow shifted in a direction opposite to that produced by the habitually worn lenses. Overall, our results represent one of the first formal reports that adjusting to putting on or taking off spectacles becomes easier over time, and may have important implications for clinical management. PMID- 27264029 TI - The effect of monocular depth cues on the detection of moving objects by moving observers. AB - An observer moving through the world must be able to identify and locate moving objects in the scene. In principle, one could accomplish this task by detecting object images moving at a different angle or speed than the images of other items in the optic flow field. While angle of motion provides an unambiguous cue that an object is moving relative to other items in the scene, a difference in speed could be due to a difference in the depth of the objects and thus is an ambiguous cue. We tested whether the addition of information about the distance of objects from the observer, in the form of monocular depth cues, aided detection of moving objects. We found that thresholds for detection of object motion decreased as we increased the number of depth cues available to the observer. PMID- 27264031 TI - Incidental splanchnic vein thrombosis: preliminary registry data. PMID- 27264030 TI - Navigating the transition from childhood to adulthood. PMID- 27264028 TI - Peripheral contrast sensitivity and attention in myopia. AB - Disruption of normal visual experience or changes in the normal interaction between central and peripheral retinal input may lead to the development of myopia. In order to examine the relationship between peripheral contrast sensitivity and myopia, we manipulated attentional load for foveal vision in emmetropes and myopes while observers detected targets with peripheral vision. Peripheral contrast detection thresholds were measured binocularly using vertical Gabor stimuli presented at three eccentricities (+/-8 degrees , 17 degrees , 30 degrees ) in a spatial 2 alternative forced choice task. Contrast thresholds were measured in young adult (mean age 24.5+/-2.6years) emmetropes (n=17; group SE: +0.19+/-0.32D) and myopes (n=25; group SE: -3.74+/-1.99D). Attention at central fixation was manipulated with: (1) a low attention task, requiring simple fixation; or (2) a high attention task, which required subjects to perform a mathematical task. We found that at 30 degrees all subjects exhibited lower contrast sensitivity (higher thresholds). In addition, myopes (Wilcoxon, p<0.01), but not emmetropes (Wilcoxon, p=0.1), had a significant decrease in sensitivity at 30 degrees during the high attention task. However, the attention dependent threshold increase for myopes was not significantly greater than for emmetropes (Wilcoxon, p=0.27). Attentional load did not increase thresholds at 8 degrees or 17 degrees for either refractive group. These data indicate that myopes experience a greater decrease in contrast sensitivity in the far periphery than emmetropes when attention is deployed in central vision. PMID- 27264032 TI - Avoidable readmission: an avoidable failure of discharge planning. PMID- 27264033 TI - Red cell alloimmunisation: incidence and prevention. PMID- 27264034 TI - Elastic compression stockings: the jury is still out. PMID- 27264035 TI - Challenges in adolescent venous thromboembolism. PMID- 27264036 TI - Clinical history and antithrombotic treatment of incidentally detected splanchnic vein thrombosis: a multicentre, international prospective registry. AB - BACKGROUND: Little information is available about the clinical history of patients with incidentally detected splanchnic vein thrombosis and its therapeutic management remains controversial. The aim of this study was to assess the risk factors, therapeutic strategies, and long-term outcomes of incidentally detected splanchnic vein thrombosis. METHODS: We analysed data from patients with incidentally detected splanchnic vein thrombosis who were enrolled in an international, multicentre, prospective cohort study of splanchnic vein thrombosis between 2008 and 2012. The study was done at 31 centres in 11 countries (Italy, South Korea, Germany, Canada, Belgium, the Netherlands, Brazil, USA, France, Israel, UK). Information about demographic characteristics, risk factors, and treatment was collected. The study outcomes during the 2-year follow up were major bleeding (International Society on Thrombosis and Haemostasis definition plus the need for hospital admission), thrombotic events (venous or arterial thromboses), and mortality. The primary analysis period was from the diagnosis of incidentally detected splanchnic vein thrombosis until the first adjudicated clinical outcome or the end of follow-up. FINDINGS: Between May 2, 2008, and Jan 30, 2012, we enrolled 177 patients with incidentally detected splanchnic vein thrombosis (median age 57 years [IQR 49-66], 118 [67%] men, 138 [78%] patients with portal vein thrombosis). The most common underlying diseases were liver cirrhosis (82 [46%] patients) and solid cancer (62 [35%] patients). Anticoagulant treatment was prescribed to 109 (62%) patients. Median duration of anticoagulation was 6 months (IQR 5-12) for patients who received parenteral anticoagulants alone and 24 months (IQR 12-24) for patients treated with vitamin K antagonists. During a median follow-up of 2 years (IQR 1-2), the incidence of major bleeding was 3.3 events (95% CI 1.7-6.3) per 100 patient-years and the incidence of thrombotic events was 8.0 events (95% CI 5.2-12.1) per 100 patient years. On-treatment incidence was 3.2 events (95% CI 1.2-8.4) per 100 patient years for major bleeding and 3.9 events (95% CI 1.6-9.5) per 100 patient-years for thrombotic events. In multivariate analysis, anticoagulant treatment as a time-dependent variable reduced the incidence of thrombotic events (hazard ratio 0.85, 95% CI 0.76-0.96) without increasing the risk of major bleeding (p>0.05). In patients with clinically suspected splanchnic vein thrombosis, the incidence of major bleeding was 3.9 events (95% CI 2.6-5.7) per 100 patient-years and the incidence of thrombotic events was 7.0 events (95% CI 5.2-9.3) per 100 patient years. INTERPRETATION: Our results show that the prognosis of incidentally detected splanchnic vein thrombosis is similar to that of clinically suspected splanchnic vein thrombosis and suggest that similar treatment strategies should be applied. FUNDING: Pfizer Canada research grant. PMID- 27264037 TI - Potentially avoidable hospital admissions in older patients with acute myeloid leukaemia in the USA: a retrospective analysis. AB - BACKGROUND: Older adults (>=60 years of age) with acute myeloid leukaemia spend a substantial proportion of their life in hospital after diagnosis. We examined reasons for their hospital admissions and identified potentially avoidable hospital admissions (PAH) in this age group in the USA. METHODS: In this retrospective analysis, we examined the reasons for hospital admissions in older patients diagnosed with and treated for acute myeloid leukaemia at two tertiary care hospitals in the USA. We included patients receiving intensive induction chemotherapy or non-intensive treatment. We excluded those with acute promyelocytic leukaemia, those seen only for a one-time consultation who received primary treatment elsewhere, and those who received supportive care alone. We identified the eligible cohort using the Dana-Farber Cancer Institute and Massachusetts General Hospital Leukemia Clinical Research Information Systems database. Practising oncologists used a consensus-driven medical record review process to identify the primary reason for each hospital admission and categorise it as potentially avoidable or not avoidable on the basis of an adaptation of Graham's criteria for PAH. We used multivariable logistic regression analyses to identify predictors of PAH. FINDINGS: Between May 1, 2005, and Dec 23, 2011, we assessed 1040 hospital admissions (excluding initial admission for diagnosis) in 329 consecutively admitted patients. The most common primary reasons for hospital admissions were: fever or infection (396 [38%]), planned admission for chemotherapy or transplantation (391 [38%]), and uncontrolled symptoms (102 [10%]). We identified 172 (27%) of 649 unplanned hospital admissions as potentially avoidable; among these admissions, 82 (48%) were readmissions because of previous premature hospital discharge, 32 (19%) because of problems that could have been managed in the outpatient setting, and 26 (15%) because of failure of timely outpatient follow-up. In a mixed logistic regression model, higher education (odds ratio 1.43 [95% CI 1.01-2.00]; p=0.04) and receipt of non intensive induction chemotherapy (1.97 [1.25-3.10]; p=0.003) were predictors of PAH. INTERPRETATION: Although many hospital admissions in older patients with acute myeloid leukaemia are unavoidable and driven by the illness course and its treatment, a substantial proportion are potentially avoidable. Future interventions to reduce PAH in this population are clearly warranted. FUNDING: National Cancer Institute, National Palliative Care Research Center, and Cambia Health Foundation. PMID- 27264039 TI - Effect of compression stockings on post thrombotic syndrome in patients with deep vein thrombosis: a meta-analysis of randomised controlled trials. AB - BACKGROUND: Whether compression stockings are effective in the prevention of post thrombotic syndrome in patients with deep vein thrombosis remains unknown. Since the recently published SOX trial, no meta-analysis has been done to re-evaluate the available literature on whether compression stockings are beneficial in these patients. We aimed to determine the effectiveness of elastic compression stockings on preventing post thrombotic syndrome in patients with deep vein thrombosis. METHODS: For this meta-analysis, we searched PubMed, the Cochrane Library, and Embase databases from inception to July 29, 2015, with no language restrictions, for randomised controlled trials comparing compression therapy with placebo (either none or placebo stockings) in patients with deep vein thrombosis. We did a meta-analysis with primary outcome as incidence of post thrombotic syndrome. Secondary outcomes analysed were mortality and recurrence of deep vein thrombosis. Sensitivity analysis was done for heterogeneity, study quality, diagnosis by Villalta scoring, and non-delayed randomisation. FINDINGS: We identified 674 reports, of which six were randomised controlled trials including 1462 patients. Use of elastic compression stockings was not associated with prevention of post thrombotic syndrome compared with controls (OR 0.56 [95% CI 0.27-1.16]; 36% [269/739] vs 45% [322/723]; p=0.12). Subgroup sensitivity analysis showed that elastic compression stockings were not associated with prevention of post thrombotic syndrome despite trying to account for heterogeneity (OR 0.63 [95% CI 0.29-1.33]; 27% [63/234] vs 37% [85/231]; p=0.23), diagnosis by Villalta scoring (0.81 [0.36-1.84]; 43% [228/535] vs 45% [235/517]; p=0.62), nor those that patients randomised within 1 month of diagnosis (0.57 [0.22-1.45]; 41% [258/631] vs 49% [304/615]; p=0.24). Secondary outcomes such as mortality (OR 0.98 [95% CI 0.68-1.41]; 10% [68/703] vs 10% [67/690]; p=0.92) or recurrence of deep vein thrombosis (OR 0.93 [95% CI 0.66-1.31]; 6.4% [70/1094] vs 6.8% [73/1066]; p=0.69) did not differ significantly between the treatment and control groups. INTERPRETATION: In patients with deep venous thrombosis, use of elastic compression stockings does not significantly reduce the development of post thrombotic syndrome, however the current body of evidence is limited and we believe at present there is equipoise and further conclusive studies are needed to establish the role of this therapy. FUNDING: None. PMID- 27264038 TI - Red-blood-cell alloimmunisation in relation to antigens' exposure and their immunogenicity: a cohort study. AB - BACKGROUND: Matching donor red blood cells based on recipient antigens prevents alloimmunisation. Knowledge about the immunogenicity of red-blood-cell antigens can help optimise risk-adapted matching strategies. We set out to assess the immunogenicity of red-blood-cell antigens. METHODS: In an incident new-user cohort of previously non-transfused, non-alloimmunised white patients receiving non-extended matched red-blood-cell transfusions in six Dutch hospitals between 2006 and 2013, we determined the cumulative number of mismatched red-blood-cell units per patient. We used multiple imputation to address missing antigen data. Using Kaplan-Meier analysis, we estimated cumulative alloimmunisation incidences per mismatched antigen dose as a measure of immunogenicity. FINDINGS: Of 54 347 patients assessed, 21 512 were included in our study. Alloantibodies occurred in 474 (2.2%) of all transfused patients, with cumulative alloimmunisation incidences increasing up to 7.7% (95% CI 4.9-11.2) after 40 units received. The antigens C, c, E, K, and Jk(a) were responsible for 78% of all alloimmunisations in our cohort. K, E, and C(w) were the most immunogenic antigens (cumulative immunisation incidences after 2 mismatched units of 2.3% [95% CI 1.0-4.8] for K, 1.5% [0.6-3.0] for E, and 1.2% [0.0-10.8] for C(w)). These antigens were 8.7 times (for K), 5.4 times (for E), and 4.6 times (for C(w)) as immunogenic as Fy(a). The next most immunogenic antigens were, in order, e (1.9 times as immunogenic as Fy(a)), Jk(a) (1.9 times), and c (1.6 times). INTERPRETATION: Red blood-cell antigens vary in their potency to evoke a humoral immune response. Our findings highlight that donor-recipient red-blood-cell matching strategies will be most efficient when primarily focusing on prevention of C, c, E, K, and Jk(a) alloimmunisation. Matching for Fy(a) is of lower clinical relevance. Variations of antigen frequencies determined by ethnic background prevent extrapolating these conclusions to non-white populations. FUNDING: None. PMID- 27264040 TI - Inhibitory effect of progesterone during early embryonic development: Suppression of myocardial differentiation and calcium-related transcriptome by progesterone in mESCs: Progesterone disturb cardiac differentiation of mESCs through lower cytosolic Ca(2.). AB - Progesterone (PG) and its derivates are used in prevention of spontaneous miscarriage. However, some studies have reported that exposure to PG and its derivates during pregnancy can cause malformations and affect both blood pressure and the cardiovascular system. The effect of PG on cardiomyogenesis of mouse embryonic stem cells (mESCs) is not well known. Expression of Pgr mRNA showed an opposite pattern of beating-ratio during differentiation. PG treatment resulted in reduction of the beating ratio to 60.45+/-1.54% from 92.17+/-2.98% in normal differentiation, reduced transcripts of heart morphogenesis and Ca(2+) binding related genes in the next generation sequencing data and significantly decreased expression levels of Ca(2+)/contraction-related genes including Ryr2, Calm2, Trpv2, and Mylk3, the intracellular Ca(2+) level, and the beating frequency. These results suggest that PG exerts inhibitory effects on differentiation of mESCs into functional cardiomyocytes. PMID- 27264041 TI - Problematic placebos in physical therapy trials. PMID- 27264042 TI - Investigation on the pitting of potato starch granules during high frequency ultrasound treatment. AB - In this paper, the pitting of potato starch granules in aqueous suspensions (1%) by high-frequency high-power ultrasound (850kHz at a power of 0.2W, 2W or 3.7W; and also 500kHz and 1MHz at a power of 2W) is reported. The number of pits per starch granules was found to be independent of the amylose content of starches, and the surface properties of starch granules as modified through SDS and ethanol washing. At 850kHz, the maximum number of pits per starch granule, for both normal and waxy starches, did not exceed 11. However, a close inspection of fractionated starch granules based on their sizes showed that there is an optimum granule size for which a maximum pit number is obtained. For example, starch granules with diameter size range of ~15 to ~30MUm had a maximum pit number (between 10 and 20 pits per granule) when sonicated (2W, 850kHz and 30min); while sonication of small (<10MUm) and very large (>45MUm) granules resulted in a smaller number of pits per granule (~5). Further, the maximum number of pits per granules is also found to be proportional to the ultrasound frequency, with values of approximately 7, 10 and 11 at 0.50, 0.85, and 1MHz, respectively. FTIR measurements did not show any breakup of starch molecules. PMID- 27264043 TI - Overlooking Informal Dementia Caregivers' Burden. AB - Patients with Alzheimer's disease (AD) need early caregiver support. Caregivers often have poor health, but usually do not have time to seek medical advice for their own conditions. Patients' physicians, who are frequently the sole medical practitioner caregivers contact regularly, have an important function in recognizing family caregivers' burdens. The current study investigated to what extent medical practitioners recognized family caregivers' problems. In a two staged survey in neurology outpatient care, caregivers of patients with mild or moderate AD were enrolled and assessed by physicians regarding their physical and mental burden, as well as need for help and advice about AD. Subsequently, caregivers' mental health was evaluated in a comprehensive diagnostic interview by blinded psychologists. Overall, 73.7% of caregivers had at least one somatic condition and 43.7% had clinically relevant depressive symptoms (of these, 37.5% met criteria for major depression). The findings suggest that the burden of a substantial proportion of affected family caregivers is overlooked. [Res Gerontol Nurs. 2016; 9(4):167-174.]. PMID- 27264044 TI - The Relationship Between Reminiscence Functions, Optimism, Depressive Symptoms, Physical Activity, and Pain in Older Adults. AB - The study purpose was to examine the association between reminiscence functions, optimism, depressive symptoms, physical activity, and pain in older adults with chronic lower extremity osteoarthritis pain. One hundred ninety-five community dwelling adults were interviewed using the Modified Reminiscence Functions Scale, Brief Pain Inventory, Life Orientation Test-Revised, Center for Epidemiologic Studies Short Depression Scale, and Physical Activity Scale for the Elderly in random counterbalanced order. Structural equation modeling supported chronic pain as positively associated with depressive symptoms and comorbidities and unrelated to physical activity. Depressive symptoms were positively associated with self negative reminiscence and negatively associated with optimism. Spontaneous reminiscence was not associated with increased physical activity or reduced pain. Individuals may require facilitated integrative reminiscence to assist them in reinterpreting negative memories in a more positive way. Facilitated integrative reminiscence about enjoyed past physical activity is a potential way to increase physical activity, but must be tested in future research. [Res Gerontol Nurs. 2016; 9(5):223-231.]. PMID- 27264045 TI - Grade and looseness of the inner cell mass may lead to the development of monochorionic diamniotic twins. AB - OBJECTIVE: To examine the relationship between the inner cell mass (ICM) grade and its morphological configuration on the occurrence of monochorionic diamniotic (M-D) twinning. DESIGN: Retrospective embryo cohort study. SETTING: Private IVF clinic. PATIENT(S): Evaluation of frozen-thawed single blastocyst transfers with hormone replacement treatment in 8,435. This cohort included 71 blastocysts and their ICMs observed by time-lapse photography. INTERVENTION(S): Any changes in configuration of the ICMs observed by time-lapse photography were analyzed retrospectively. MAIN OUTCOME MEASURE(S): The amount of loosening of blastomeres within the ICM was evaluated by time-lapse observations. The number of cells that were involved in the loosening process was also assessed. Both of these parameters were correlated with the type of monozygotic twinning that eventuated. RESULT(S): The M-D twinning incidence resulting from blastocysts with a high grade ICM (grade A) were transferred was 0.38% (3/796), whereas it was significantly higher, 1.38% (34/2,463), when blastocysts with a poorer (B and C) grade ICM were transferred. Among 71 transferred frozen-thawed blastocysts that were studied with time-lapse photography, there were two dichorionic diamniotic and one M-D twins. Careful observations of the embryo that resulted in the one M D case, revealed that the ICM acquired a looser appearance due to decompaction of at least eight cells. This type of decompaction was not observed in the ICMs of other transferred blastocysts. CONCLUSION(S): The occurrence of M-D twinning may be avoided by excluding blastocysts that contain decompacting ICMs. PMID- 27264046 TI - Anticipating things to come. PMID- 27264048 TI - Introduction: Population and Health Services Research. PMID- 27264047 TI - Gastrin regulates ABCG2 to promote the migration, invasion and side populations in pancreatic cancer cells via activation of NF-kappaB signaling. AB - Gastrin is absent in most normal adult pancreatic tissues but is highly expressed in pancreatic cancer tissues. Although Gastrin expression was reported to be associated with tumor proliferation in human pancreatic cancer, studies on the relationship between Gastrin and tumor metastasis in pancreatic cancer are rare. In this study, we performed an analysis to determine the effects of Gastrin on modulating the side populations, cell proportion and tumor cell metastatic potential and invasion activity and explored its mechanisms in pancreatic cancer. We indicated that Gastrin and ABCG2 were widely expressed in pancreatic cancer cell lines and overexpressed in cancer tissues. Gastrin induced ABCG2 expression, and this effect was mediated by NF-kappaB activation. Gastrin regulated the SP proportion of BxPC-3 cells via modulating ABCG2 expression. Through the regulation of the functions of NF-kappaB/ABCG2, Gastrin functionally promoted the migration and invasion in pancreatic cancer cell. The present study indicated that Gastrin induced ABCG2 expression by activating NF-kappaB and thereby modulated the SP proportion, tumor cell metastatic potential and invasion activity in pancreatic cancer. Gastrin could serve as an effective therapeutic target for the metastasis of pancreatic cancer. PMID- 27264049 TI - Impact of concomitant hernia repair at the time of complete primary repair of bladder exstrophy. AB - BACKGROUND: Inguinal hernias are common in the bladder exstrophy population. As these hernias may present with incarceration following bladder closure, several groups recommend inguinal exploration and hernia repair at the time of initial bladder closure. However, the benefits of such an approach are not well defined. In 2006, we modified our approach to this condition by routinely performing concomitant inguinal herniorraphy (CIH) repair at the time of initial exstrophy repair. The aim of this study was to test the hypothesis that simultaneous inguinal hernia repair will be safe and effective in reducing subsequent unplanned inguinal procedures in this high-risk group. METHOD: We conducted a retrospective chart review of patients with classic bladder exstrophy managed with complete primary repair (CPRE) from 1990 to 2014, with focus on inguinal hernia repair at the time of bladder closure and subsequent need for inguinal surgery. We excluded patients with follow-up less than 6 months, missing data with regards to the initial inguinal approach at the time of bladder closure, and patients with intra-abdominal testicles. RESULTS: A total of 43 patients were included for analysis with 27 (61%) having inguinal hernias identified either at birth or in subsequent follow-up, including 20 of 27 boys and 7 of 16 girls. A summary of comparison groups with and without CIH at the time of CPRE, as well as follow-up and need for subsequent hernia repair, is given in the summary Table. Of 25 patients without concomitant inguinal herniorraphy at CPRE, 10 patients required subsequent inguinal surgeries for inguinal herniorraphy (seven), orchiopexy (one), or inguinal herniorraphy plus orchiopexy (two). CONCLUSION: CIH at the time of CPRE is safe, with no significant inguinal complications noted. Subsequent inguinal operations were more often required in the cohort of patients not receiving CIH at the time of CPRE, including one patient presenting with incarceration. Thus, CIH appears to reduce need for subsequent inguinal operations when performed at the time of bladder closure. Our study adds to other authors' claims that CIH should be attempted at the time of bladder closure. This study is limited by the retrospective nature of the review and differences in follow-up times between groups. Simultaneous inguinal hernia repair at the time of initial exstrophy repair is safe and associated with decreased incidence of subsequent inguinal surgery. Such an approach should be undertaken during initial bladder closure. PMID- 27264050 TI - Testicular prostheses in children: Is earlier better? AB - INTRODUCTION: The absence of a testis occurs for various reasons in children, but testicular prosthesis implantation in children is uncommon. The optimal time for prosthesis placement is still unclear, and its complication rate has been poorly studied in children. OBJECTIVE: The aim of this study was to determine the risk factors of complications in cases of testicular prosthesis implantation in children. STUDY DESIGN: A monocentric, retrospective review was performed of children implanted with a testicular prosthesis between 2008 and 2014. All implantations were performed through an inguinal incision with a standardized procedure. Children were divided into two groups depending on the interval after orchiectomy: (A) early implantation (delay between surgeries <1 year); and (B) delayed surgeries (delay >=1 year). Statistical analysis was performed with Student and Fisher tests. RESULTS: Twenty-six patients (A, 15; B, 11) had a total of 38 testicular prostheses placements. Mean follow-up was 36.2 months. First surgery was performed at the mean age of 11.8 years (range 0-17.9) (A, 14.1; B, 8.1; P = 0.01) and testicular prosthesis implantation at the mean age of 14.7 years (range 9-18) (A, 14.3; B, 14.6) with a mean delay of 36.1 months (A, 1.3; B, 80.3). Indications were mainly spermatic cord torsion (27%), bilateral anorchia (27%), and testicular atrophy after cryptorchidism surgery (19.2%). Complications (10.5%) included two cases of extrusion, one infection and one migration. Patient 1 had a history of acute lymphoblastic leukemia with testicle relapse 2 years after induction therapy. High-dose chemotherapy, total body irradiation and bilateral orchiectomies were performed, and bilateral prostheses were implanted 12 years after the end of chemotherapy. Complications happened 85 days after surgery. Patient 2 was followed-up for a proximal hypospadias. The tunica vaginalis flap, which was used during a redo urethroplasty, lead to testicular atrophy. Thirteen years after the last penile surgery, a testicular prosthesis was placed through an inguinal incision, and extrusion occurred 203 days after surgery. Bacterial cultures of the prostheses were sterile and histological review showed no sign of granuloma or graft rejection. The complication rate was significantly higher if the delay between the two surgeries exceeded 1 year (P = 0.01). Indications of orchiectomy, prior scrotal incision, and prosthesis size were not risk factors. CONCLUSIONS: Testicular prosthesis implantation was relatively safe in a pediatric cohort. The complication rate was significantly higher if the delay between the orchiectomy and the prosthetic placement exceeded 1 year. These results suggest that reducing the delay between orchiectomy and prosthesis implantation may lead to fewer complications. PMID- 27264051 TI - Mini-percutaneous nephrolithotomy with high-power holmium YAG laser in pediatric patients with staghorn and complex calculi. AB - INTRODUCTION: Shock wave lithotripsy (SWL) is the treatment of choice for most cases of renal lithiasis in children. Some cases, however, are refractory to SWL and may be associated with anatomic and metabolic changes or a large stone burden. In these circumstances, mini-percutaneous nephrolithotomy (mini-PCNL) is an option. OBJECTIVE: The aim was to assess the safety and efficacy of high-power holmium YAG (Ho:YAG) laser in mini-PCNL for staghorn calculi. PATIENTS AND METHODS: The clinical records relating to 35 mini-PCNLs (Table) performed between January 2008 and December 2012 in 33 patients (27 boys and 6 girls; mean age 7 years, range 2-18 years) were retrospectively reviewed. Twenty-two (66.7%) of the patients had undergone a previous SWL (28.6% three sessions). The mini-PCNL puncture technique used involved fluoroscopic guidance with the C arm at 0-90 degrees in the supine position. An 18F tract was used. Stone fragmentation was performed with a high-power Ho:YAG laser (Lumenis 100 W). RESULTS: Ten of the mini-PCNLs (28.6%) were right sided, and 25 were left sided (71.4%). Stones were located in the lower calyceal group in 64% of patients and in the renal pelvis in 50%. The mean stone size was 4.46 cm(2) (range 3-13.20 cm(2)). The number of stones varied between one and 20, and 83.3% were radiopaque. The laser was set at 70 W (range 50-100 W) (3.5 J/pulse with a frequency of 20 pulses/s). The mean surgical time was 150 min. In 78% of patients, complete stone clearance was achieved, and the overall stone-free rate rose to 85% when residual stones were treated with either SWL or retrograde intrarenal surgery. No perioperative complications were seen. DISCUSSION: There are few reports in the literature concerning the use of a high-power laser for treatment of complex stones and the few that do exist relate to adults have similar results, showing it to be highly effective and safe, with low morbidity. Some limitations of the present study must be acknowledged. It was retrospective and a relatively small number of patients were included. However, randomized prospective studies are required to confirm our findings and conclusions. CONCLUSION: In the pediatric population, mini-PCNL with high-power Ho:YAG laser is feasible and safe and represents the technique of choice for complex renal stones. PMID- 27264052 TI - Impact of Obesity on Cardiopulmonary Disease. AB - Although there are known detrimental effects of obesity on the heart and lungs, few data exist showing obesity as risk factor for cardiopulmonary disorders in dogs and cats. It is probable that increased abdominal fat is detrimental as it is in humans, and there is evidence of negative effects of increased intrathoracic fat. As well as physical effects of fat, increased inflammatory mediators and neurohormonal effects of obesity likely contribute to cardiopulmonary disorders. Weight loss in overweight individuals improves cardiac parameters and exercise tolerance. Obesity in patients with obstructive airway disorders is recognized to increase disease severity. PMID- 27264053 TI - Scope of the Problem and Perception by Owners and Veterinarians. AB - Obesity is a common disease of modern dogs and cats. Dog and cat owners often do not realize their animal is affected. Some pet owners are skeptical of the diagnosis or rationalize the overweight condition of their pets. Animal-related factors associated with obesity in dogs and cats include breed, neuter status, age, and gender, whereas owner-related factors include diet choice, feeding method, and provision of exercise. Owner characteristics, such as age and income, are also potential risk factors for pet obesity. Identifying such risk factors for both animals and owners may help provide targets for prevention or interventional tools. PMID- 27264054 TI - Obesity Treatment: Environment and Behavior Modification. AB - Obesity is commonly encountered in veterinary patients. Although there are various published dietary approaches to achieving weight loss, successful long term prevention of weight regain has proven elusive. Adding environmental and behavioral treatment strategies to a weight loss plan may help the veterinary team, the pet, and the pet owner maximize the effectiveness of the program. Because the owner directly affects the environment and behavior of the pet undergoing a weight loss plan, treatment strategies with an emphasis on owner involvement is the focus of this review. Veterinary use of the 5 A's behavioral counseling approach with the pet owner is discussed. PMID- 27264055 TI - Communicating with Pet Owners About Obesity: Roles of the Veterinary Health Care Team. AB - Obesity continues to be the most prevalent nutritional problem of dogs and cats as well as one of the most frustrating conditions to treat successfully. Educating and assigning roles to all members of the health care team will improve staff engagement and the consistency and effectiveness of nutritional counseling for preventive care and weight loss treatment plans. Excellent communication skills can be used to assess the client's ability to change and implement a weight loss plan at the right time in the right way to achieve better adherence and improve patient health. PMID- 27264057 TI - Electrocatalytic reduction of CO2 using Mn complexes with unconventional coordination environments. AB - New complexes, Mn{kappa(3)-[2,6-{Ph2PNMe}2(NC5H3)]}(CO)3(+)Br(-) (1(+)Br(-)) and MnBr{kappa(2)-(Ph2P)NMe(NC5H4)}(CO)3 (2), are reported and present new ligand environments for CO2 electrocatalytic reduction to CO. Compound 1(+) presents a unique metal geometry for CO production (96%) in the absence of added water while 2 required addition of water and generated both CO and H2 products. PMID- 27264056 TI - Genetic influences on phase synchrony of brain oscillations supporting response inhibition. AB - Phase synchronization of neuronal oscillations is a fundamental mechanism underlying cognitive processing and behavior, including context-dependent response production and inhibition. Abnormalities in neural synchrony can lead to abnormal information processing and contribute to cognitive and behavioral deficits in neuropsychiatric disorders. However, little is known about genetic and environmental contributions to individual differences in cortical oscillatory dynamics underlying response inhibition. This study examined heritability of event-related phase synchronization of brain oscillations in 302 young female twins including 94 MZ and 57 DZ pairs performing a cued Go/No-Go version of the Continuous Performance Test (CPT). We used the Phase Locking Index (PLI) to assess inter-trial phase clustering (synchrony) in several frequency bands in two time intervals after stimulus onset (0-300 and 301-600ms). Response inhibition (i.e., successful response suppression in No-Go trials) was characterized by a transient increase in phase synchronization of delta- and theta-band oscillations in the fronto-central midline region. Genetic analysis showed significant heritability of the phase locking measures related to response inhibition, with 30 to 49% of inter-individual variability being accounted for by genetic factors. This is the first study providing evidence for heritability of task-related neural synchrony. The present results suggest that PLI can serve as an indicator of genetically transmitted individual differences in neural substrates of response inhibition. PMID- 27264059 TI - International variability in diet and requirements of manganese: Causes and consequences. AB - Manganese (Mn) is an essential trace element that is critical for human health and development. At the turn of the century when diets were based on whole grains, cereals and other traditional foods, Mn intakes (8-9mg/d) were much greater than that prevalent today (2mg/d). As societies have developed, diets have shifted as part of a nutrition transition, to those that are high in processed foods, fat, and sugar. These foods are virtually devoid of Mn. Thus, dietary Mn has declined substantially throughout the world, as confirmed by several wide-scale, total diet studies. International variability in dietary Mn is considerable, due to tremendous diversity in food and culture. In countries where fruit and vegetable intake may be limited, i.e. the United Kingdom, populations may ingest much lower levels of Mn (1.4mg/d) as compared to Asian cultures (4mg/d) which have an abundance of plant foods in their food supply and cuisine. The bioavailability of Mn must be considered, including chemical form, oxidation state, mineral-mineral interactions, presence of dietary components and traditional food processing techniques (milling, germination, malting, fermentation). Manganese toxicity is a public health problem that results from exposure to a naturally high water source or contaminated environment of the soil and/or drinking water. In contrast, inadequate intake is associated with adverse health effects such as diabetes, metabolic syndrome, poor birth outcomes and possibly, cancer. Future studies are recommended to set dietary standards for this mineral in countries that lack recommendations to help achieve optimal health. PMID- 27264061 TI - Prevalence of Beta Thalassemia Trait in Denizli. AB - Beta thalassemia, characterized by the deficiency or the absence of beta globulin production, is the most widespread inherited disorder in the world and is also common in Turkey. To determine the prevalence of carriers for beta thalassemia, we screened the couples before their marriage. For this aim, from 1994 to 1999, a total of 14.200 people were screened. The complete blood count and red blood cell indices (hemoglobin: Hb, hematocrite: Hct, median corpusculer volume: MCV, median corpusculer hemoglobin: MCHb, median corpusculer hemoglobin concentration: MHbC, concentration were measured by automated cell counter on the same day of collection. Then for the samples with MCV values of 78 fL or below, hemoglobin electrophoresis were employed. Testing for beta thalassemia was carried out by the conventional cellulose asetate electropheresis at pH 8.4. People who have elevated HbA2 (>= 3.5%) were accepted as beta-thalassemia carrier or patient. We detected 3300 people with MCV levels of 78 fL or below and 311 cases of beta thalassemia carrier and 11 cases of beta thalassemia. The prevalence of carriers for beta thalassemia in Denizli was 2.2%. This result indicated that the people with anemia in our region should be investigated for the existence of hemoglobinopathy. PMID- 27264060 TI - Screening of Hemoglobinopathies in Kahramanmaras, TURKEY. AB - Thalassemia and sickle cell anemia are prevalent in southern Turkey. Being in close proximity to Cukurova we screened Kahramanmaras to assess the prevalence and foci of the diseases. The sample sizes were calculated by EpiInfo 6.0 computer program at 95% confidence level. 1491 subjects aged 2-69 were studied. Hematological parameters were analyzed by an electronic cell counter. Electrophoresis were performed and Hemoglobin A2 and hemoglobin F levels were determined on samples with MCV< 80 fL. The results of Canatan et al. on Elbistan were included in the final results. Thus, the prevalence of beta-thalassemia, hemoglobin D, Hemoglobin O Arab carriers were 0.68%, 0.28% and 0.013%, respectively. No hemoglobin S was detected. In conclusion, Kahramanmaras seems not to be a high risk area but the public must be informed about these diseases. Every community in close proximity to high prevalence areas must be enlightened. PMID- 27264058 TI - The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial. AB - OBJECTIVE: Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess whether vitamin D supplementation can slow the rate of progression. METHOD: A 3-year, double-blind, randomised, placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing 800 IU cholecalciferol daily with placebo. Primary outcome was difference in rate of medial joint space narrowing (JSN). Secondary outcomes included lateral JSN, Kellgren & Lawrence grade, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, stiffness and the Get up and Go test. RESULTS: Vitamin D supplementation increased 25-OH-D3 from an average of 20.7 (standard deviation (SD) 8.9) MUg/L to 30.4 (SD 7.7) MUg/L, compared to 20.7 (SD 8.1) MUg/L and 20.3 (SD 8.1) MUg/L in the placebo group. There was no significant difference in the rate of JSN over 3 years in the medial compartment of the index knee between the treatment group (average -0.01 mm/year) and placebo group (-0.08 mm/year), average difference 0.08 mm/year (95% confidence interval (CI) [-0.14-0.29], P = 0.49). No significant interaction was found between baseline vitamin D levels and treatment effect. There were no significant differences for any of the secondary outcome measures. CONCLUSION: Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain, stiffness or functional loss over a 3-year period. On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA. PMID- 27264062 TI - Rapid Identification of Family-Specific Mutations in the Factor VIII Gene by One Step DGGE. AB - A one-step denaturing gradient gel electrophoresis (DGGE) strategy for the rapid detection of mutations in the factor VIII gene of haemophilia A patients is described. All coding (except the middle part of exon 14) and flanking intronic regions of the gene corresponding to approximately 6.6 kb were amplified in 27 fragments using four PCR programs. Heteroduplex formation was performed for each fragment. A common denaturant gradient gel (35-65%) was chosen that allowed the simultaneous analysis of all PCR amplified regions on a single gel and run for 3.5 h at 160 V. This method was implemented for a patient whose family was seeking carrier determinations. An abnormal pattern was detected in exon 23 and the family-specific mutation was found by subsequent DNA sequencing. One-step DGGE is a promising rapid method for the carrier detection and prenatal diagnosis in haemophilia A families when immediate results are required and when polymorphic markers fail to give information. PMID- 27264063 TI - The Hemostatic Changes in Active Pulmonary Tuberculosis. AB - Severe pulmonary tuberculosis (PTB) is sometimes complicated with deep venous thrombosis (DVT). We have examined the role of possible hemostat>c disturbance, which are predisposing factors for venous thrombosis in patients with PTB. Coagulation and platelet function tests have been studied in 40 patients with severe PTB and 40 healthy control volunteers before therapy and they were compared with 30th day results and controls. Analysis in patients with active PTB showed anemia, leucocytosis, thrombocytosis, elevation in plasma fibrinogen, factor VIII, plasminogen activator inhibitor 1 (PAI-1) with depressed antithrombin III (ATIII) and protein C (PC) levels. On the 30th day of treatment, anemia, leucocytosis and thrombocytsis were improved. Fibrinogen and factor VIII levels decreased to normal levels, PC and AT III levels increased to normal levels whereas there was no difference in PAI-1 levels. Platelet aggregation studies demonstrated increased platelet activation. Activated protein C resistance was not determined. DVT was not detected in patients during the follow up period. Decreased AT III, PC and elevated plasma fibrinogen levels and increased platelet aggregation appear to induce hypercoagilable state seen in PTB and improves with tretament. PMID- 27264064 TI - Long Term Low Dose Maintenance Chemotherapy in the Treatment of Acute Myeloid Leukemia. AB - In this study the effect of low dose long-term maintenance chemotherapy in patients with acute myeloid leukemia (AML) was evaluated. Following a complete remission two consolidation courses were given with the same drugs. Thereafter patients received low dose maintenance chemotherapy in every four weeks until disease relapsed or for up to two years. A total of 68 patients were evaluated. The median duration of remission of 22.5 months in patients who received maintenance chemotherapy while it was only 7 months in those without maintenance chemotherapy after a median follow-up time of 71 months, which was significant. Overall survival (OS) was also significantly longer in patients with maintenance therapy. Similar results were also obtained in comparison of patients over 60. Thus, it was concluded that maintenance therapy might be beneficial for older AML patients with limited therapy choice. PMID- 27264065 TI - Clinical, Immunophenotypic and Cytogenetic Features of Megakaryocytic Blast Crisis of Chronic Myeloid Leukemia: A Single Institution Study. AB - We present 15 patients with megakaryocytic (Mk) blast crisis (BC) of a Philadelphia (Ph) chromosome positive CML confirmed by immunophenotype analysis between 1989-2000. The primary aim of this study is to define clinical, immunological, cytogenetic and laboratory characteristics of Mk BC in Ph positive CML. We have done retrospective analysis regarding basic clinical findings, immunologic phenotype, cytogenetic studies and platelet functions. All patients had significant expression of CD61 (14/14) and CD34 (13/13) antigens, and a high frequency of expression of CD13 (9/12), CD33 (10/12) and CD11b (9/11). The BC in 6/15 patients was presented with thrombocytosis, 7/15 had a normal platelet count and two patients had thrombocytopenia. A grade IV myelofibrosis was present in 8/10 patients. Six patients evolved additional karyotypic abnormalities. Two patients had extramedullary BC. The serum activity of LDH (med. 1095.6) was elevated in all patients. A platelet dysfunction was documented in 4/5 patient tested. There are no clinical and hematological characteristics specific for Mk BC of CML. Normal or elevated platelet count (med. 427.4 x 109/L) in BC of CML with prominent expression of CD34 and CD61 antigens, and significant myelofibrosis (grade IV) are the most consistent clinical findings. PMID- 27264066 TI - Hodgkin's Disease: Results of a Single Center in Central Anatolia. AB - Hodgkin's Disease (HD) accounts for about 1% of newly diagnosed malignant diseases. In this study 119 HD cases followed in Erciyes University Hospital were evaluated. 67.2% of the patients was male, 32.8% female. The patients' age ranged from 15 to 72 years with a median of 41.5 years. Of the patients 10.1% was stage I, 29.4% stage II, 39.5% stage III, and 21.0% stage IV. According to Rye classification frequency of histologic subtypes was as follows; 21.0% lymphocyte predominant, 25.2% nodular sclerosis, 43.7% mixed cellularity, and 10.1% lymphocyte depletion. Combination chemotherapy consisting cyclophosphamide, vincristine, procarbazine and prednisolone (COPP) was used as first line treatment in 59.7% of patients. Complete remission was achieved in 84.9% of patients and partial remission in 5.0% of patients; response could not be obtained in remaining 10.1% of patients. Disease progression or recurrence was observed in 30.2% of patients. Five year survival rate was found as 70.8% of all patients, 90.1% for stage I-II, 55.3% for stage III-IV patients (p= 0.03). PMID- 27264067 TI - Epstein-Barr Virus Latent Membrane Protein 1 (LMP-1) in Hodgkin's Lymphoma Patients in Turkey. AB - Epstein-Barr virus (EBV) has been implicated as a contributing factor in the development of Hodgkin's lymphoma. The aim of this study was to elucidate the association of Hodgkin's lymphoma with EBV in a Turkish population using immunohistochemical detection of LMP-1. We studied a total of 21 consecutive cases of Hodgkin's lymphoma from Turkey. LMP-1 protein was detected in 9 of 21 (42.8%) cases. LMP-1 was positive in 4 of 7 (57%) mixed cellularity and 5 of 13 (38.4%) nodular sclerosis subtype. The results of the current study suggests a strong association of Epstein-Barr virus with Hodgkin's lymphoma in Turkey and, together with those reported previously showed that Epstein-Barr virus correlated with mixed cellular type, with a slight male predominancy while there was no correlation with age. PMID- 27264068 TI - Myelotoxicity of Cyclophosphamide, Methotrexate and 5-fluorouracil Regimen in the Early Stage Breast Cancer Patients with Diabetes Mellitus. AB - CMF (cyclophosphamide, methotrexate and 5-fluorouracil) is one of the most commonly used chemotherapy (CT) regimens in breast cancer. To the best of our knowledge there are no published studies on the toxicity of this regimen in the existence of diabetes mellitus (DM), in the literature. We retrospectively analyzed the myelotoxicity of CMF CT after 40 adjuvant cycles of 18 diabetics, according to WHO toxicity scala. Leucopenia/granulocytopenia was the most prominent toxicity (observed in overall 30% of the cycles), but it was relatively mild (5% grade III and 2.5% grade IV granulocytopenia). Anemia was only grade I (10% of the cycles), and there was no trombocytopenia. Two of the cases with grade III and IV granulocytopenia, had grade I and II urinary tract infections respectively, following the CT. The case with grade IV granulocytopenia and infection had received G-CSF. We conclude that CMF regimen is tolerable in DM as regard to its myelotoxicity. However, the patients should be closely monitored as infections may easily arise in parallel to deepening leucopenia in DM. Further extended studies would be appropriate on the toxicity of CMF as well as the other common CT regimens in DM. PMID- 27264069 TI - The Frequency of Pneumocystis carinii in Patients with Haematologic Malignancies and Pneumonia. AB - Pneumocystis carinii (P. carinii) is an organism which was previously considered as a protozoan but recently it was shown to be more related to fungi. P. carinii increasingly causes opportunistic infections in immunocompromised patients. In this study, we detected P. carinii oocysts by indirect immunofluorescence test in 33 specimens obtained from 31 patients with haematological malignancies who had symptoms of pneumonia and investigated probable risk factors (corticosteroid usage, neutropenia duration, severe or mild neutropenia and type of haematological malignancy) for P. carinii pneumonia in P. carinii (+) patients. Although not statistically significant, PCP incidence was higher in relapsed acute leukemia (AL) patients (62.5%), patients with prolonged neutropenia (57.1%), and who received high dose ARA-C therapy (62.5%). P. carinii (+) patients were treated with trimethoprim-sulfamethoxazole. Six patients with PCP did not respond to therapy and died (50%). In conclusion PCP is not infrequent in AL (especially relapsed AL) and, indirectly we can suggest that chemoprophylaxis may be considered for these patients when they were in severe and prolonged neutropenia after high dose ARA-C therapy. PMID- 27264070 TI - Homozygous beta-Thalassemia (FCS8-AA) and Hereditary Spherocytosis in the Same Patient. AB - A three-year old Turkish girl having both homozygous beta-thalassemia and hereditary spherocytosis and her family have been studied. The molecular defect causing thalassemia in the family was of the frame shift codon 8 (-AA) mutation type. The diagnosis of hereditary spherocytosis is based on osmotic fragility test in the patient and the family. However, the examination of erythrocyte membrane proteins has not been possible. betathalassemia is in the heterozygous form in the mother, the father, and in two sisters. The mother, the father, and one of the sisters also have hereditary spherocytosis in addition to thalassemia. All those family members are asymptomatic. However, the patient who has frame shift codon 8 homozygosity along with hereditary spherocytosis presented with a severe form of hemolytic anemia. PMID- 27264071 TI - Successful Surgical Management of Typhlitis in a Patient with Acute Myeloblastic Leukemia. AB - Typhlitis (neutropenic enterocolitis) is a potentially life-threatening complication associated with neutropenia and combination chemotherapy. The incidence of this disease is increasing in both patients with hematologic malignancies and solid tumors with the advent of more aggressive chemotherapy. Here, we describe a patient with acute myeloblastic leukemia in whom typhlitis developed during induction chemotherapy and managed successfully with both medical and surgical intervention during neutropenic period. Our experience reinforces prior reports that intense medical treatment, close observation and emergent surgical intervention has been shown to be life saving. PMID- 27264072 TI - Images in Haematology. PMID- 27264073 TI - Circulating follistatin in relation to energy metabolism. AB - Recently, substantial evidence has emerged that the liver contributes significantly to the circulating levels of follistatin and that circulating follistatin is tightly regulated by the glucagon-to-insulin ratio. Both observations are based on investigations of healthy subjects. These novel findings challenge the present view of circulating follistatin in human physiology, being that circulating follistatin is a result of spill-over from para/autocrine actions in various tissues and cells. Follistatin as a liver derived protein under the regulation of glucagon-to-insulin ratio suggests a relation to energy metabolism. In this narrative review, we attempt to reconcile the existing findings on circulating follistatin with the novel concept that circulating follistatin is a liver-derived molecule regulated by the glucagon-to insulin ratio. The picture emerging is that conditions associated with elevated levels of circulating follistatin have a metabolic denominator with decreased insulin sensitivity and/or hyperglucagoneimia. PMID- 27264074 TI - miR-451 suppresses the NF-kappaB-mediated proinflammatory molecules expression through inhibiting LMP7 in diabetic nephropathy. AB - Activation of nuclear factor -kappa B (NF-kappaB) is associated with inflammation in the progression of diabetic nephropathy (DN). MiR-451 is closely linked to renal damage in DN. Large multifunctional protease 7 (LMP7), an immunoproteasome subunit, can activate NF-kappaB. However, it remained unclear whether miR-451 affected NF-kappaB-induced inflammation by regulating LMP7 in DN. In this study, deep sequencing, in situ hybridization, quantitative real-time PCR, dual luciferase reporter gene assays, western blot and chromatin immunoprecipitation were respectively used. For the results, we found that miR-451 was markedly downregulated in the kidneys of db/db mice, PBMCs of DN patients and mesangial cells (MCs) cultured in high glucose conditions. Furthermore, miR-451 directly targeted LMP7 expression to inhibit NF-kappaB activity, and down-regulated transcription of proinflammatory molecules in MCs. More importantly, in the kidneys of db/db DN mice, increasing miR-451 level inhibited LMP7/NF-kappaB activity, and attenuated the urinary microalbumin excretion, blood glucose, and glomerular injury. In conclusion, these results provide new insights into the regulation of miR-451 via the LMP7/NF-kappaB central inflammatory pathway during progression of DN. PMID- 27264076 TI - Off-equilibrium surface tension in miscible fluids. AB - The interfacial tension between immiscible fluids is responsible for a wealth of every-day phenomena, from the spherical shape of small drops and bubbles to the ability to walk on water of many insects. More than a century ago, physicist and mathematician D. Korteweg postulated the existence of an effective interface tension for miscible fluids, whenever a composition gradient exists, as encountered, e.g., in many flow geometries. In this mini-review, we discuss experimental work performed in the last decades that demonstrates the existence of a positive effective interface tension in a variety of systems, from molecular, near-critical liquids to complex fluids such as polymer solutions and colloidal suspensions. The various experimental strategies that have been deployed are discussed, together with their advantages and limitations. Finally, some of the key theoretical questions still open are outlined. PMID- 27264075 TI - Zinc alpha2 glycoprotein alleviates palmitic acid-induced intracellular lipid accumulation in hepatocytes. AB - Zinc alpha2 glycoprotein (ZAG) plays an important role in stimulating fat mobilization and lipolysis in adipose tissue, but its role in hepatic lipid metabolism remains unclear. Palmitic acid (PA) was used to stimulate HepG2 cells with ZAG overexpression or ZAG knock down (shRNA). Overexpression of ZAG significantly inhibited lipogenesis, promoted lipolysis and fatty acid beta oxidation, and attenuated PA-induced intracellular fat accumulation. Moreover, ZAG overexpression dramatically stimulated adiponectin expression in HepG2 cells. In contrast, knockdown of ZAG notably inhibited fatty acid beta-oxidation, increased lipogenesis and lipid accumulation. Collectively, these data suggest that ZAG has the potential to alleviate hepatosteatosis, making it a promising therapeutic target for fatty liver. PMID- 27264077 TI - Corrigendum to 'A preoperative personalized risk assessment calculator for elderly ovarian cancer patients undergoing primary cytoreductive surgery' Gynecol. Oncol. 139 (2015) start 401-406. PMID- 27264078 TI - From the Editor. PMID- 27264079 TI - Thalassemia major and consanguinity in Shiraz city, Iran. AB - Beta-thalassemia is among the most common genetic disorders in the world and in Iran, with widespread occurrence. A cross-sectional study on 648 beta-thalassemia patients in Shiraz, Iran was carried out to determine the demography of beta thalassemia major in Shiraz city, Fars province, Iran and also the rate of consanguinity and the significance of pre-marriage counseling in decreasing familial marriages and consequently preventing this autosomal recessive genetic disease. All interviewed patients had thalassemia major and their age, sex, and the consanguinity between parents were recorded. 40.6% of beta-thalassemia patients were outcomes of first-cousin marriages. Comparison of the percentages of familial marriages (consanguinity) between parents of beta-thalassemia patients and a sample of normal population, revealed a statistically significant difference (p< 0.00001). A nonstatistically significant difference was observed between male (53.5%) and female (46.5%) thalassemia patients. Comparison of data with the situation in 22 years ago revealed a 16.4% decrease in familial marriages among thalassemic families, however, more education and awareness of young women and men about the increased risk of beta-thalassemia after familial marriage through pre-marriage counseling is still necessary. PMID- 27264080 TI - The investigation of the effect of Marafl powder (smokeless tobacco) on hematological parameters. AB - Nicotine is used in different forms including smokeless tobacco. A special kind of smokeless tobacco also known as Maras powder (MP) is widely used in southeastern region, especially Kahramanmaras, Gaziantep and other southeastern cities of Turkey. The aim of this study was to investigate the effect of nicotine on hematological parameters in MP users. Ninety-two MP users from Kahramanmaras and its environs and sixtyeight healthy controls who did not use MP were included in the study. We measured haematological parameters in the blood samples of MP users and controls. Our results showed that while iron and WBC levels were higher in MP users than the controls (p< 0.001), monocyte and platelet counts were lower (p< 0.05 and p< 0.001, respectively). Increased leukocyte counts in MP users may be an indicator of the present inflammatory events in various tissues. So, we assume that MP, because of either high nicotine content or high tobacco-specific nitroso amines levels (TSNA), causes chronic inflammatory changes in various cells, organs and systemic circulation. PMID- 27264081 TI - The effect of transfusion on pulmonary function tests in patients with thalassemia. AB - Our aim in this study was to investigate the effects of transfusion on pulmonary function tests (PFT) in patients with thalassemia. A total of 43 patients (34 major, 6 intermedia and 3 S/B thalassemics), 21 females and 22 males aged 6 to 29 (mean +/- SD: 13.82 +/- 4.96) years participated. PFT was performed using a spirometry (ST-250) programmed with European Community for Coal and a Steal (ECCS) equations. Transfusion did not effect the PFT parameters at the pre- and posttransfusion period and but the type of pulmonary function disorders partially changed after transfusion in our patients. PMID- 27264082 TI - The pattern of expression of the apoptotic inducer Fas and the apoptotic inhibitor bcl-2 oncogenes immunohistochemicaly in bone-marrow invaded by the non Hodgkin lymphomas. AB - Apoptosis is a feature commonly seen in tumors; it is an actively regulated cellular process that leads to cell death, in fact the ability to resist apoptosis may seem to offer an advantage to a growing tumor by slowing down the cell loss rate. The present study is a retrospective study aiming at evaluating the Fas/Apo-1, CD95 and bcl-2 oncoproteins immunohistochemically in 30 bone marrow tissue specimens invaded by non- Hodgkin lymphomas (stage IV), 60% of cases were under chemotherapy regimen, while the remainders were still. The study included the significance of the apoptotic inducer Fas/CD95 and apoptotic inhibitor bcl-2 immunoreactivity in relation to a number of clinicopathological variables including age, sex, pattern of malignant cell infiltration in bone marrow, type of malignant cells disseminated and the effect of chemotherapy in relation to apoptotic changes. Fas/CD95 immunoreactivity was positive in 23 cases; 76.7%, positive immunoreactivity was significantly associated with the chemotherapeutic effect (p= 0.0002). On the other side bcl-2 immunoreactivity was positive in 7 cases; 23.3%. A significant association was found between bcl-2 positive immunoreactivity and sex (p= 0.03), pattern of malignant cell infiltration in bone marrow (p= 0.02) and lack of therapy effects (p= 0.0004). As a conclusion (1) Apoptosis is a common feature in non-Hodgkin 's lymphomas as confirmed by the high incidence of the apoptotic inducer Fas/CD95 positive immunoreactivity; (2) Fas/CD95 and bcl-2 as a tumor markers may work as a useful aid in establishing an apoptosis interpretation in cases of non-Hodgkin 's lymphomas (stage IV); (3) Fas/CD95 expression translate the chemotherapeutic effects on malignant cells in non-Hodgkin 's lymphomas; meanwhile the apoptotic inhibitor bcl-2 expression is an independent negative prognostic marker that has been shown to confer resistance to apoptosis. PMID- 27264083 TI - Further observation of Hemoglobin Beograd (B121 Glu-Val) in Turkish population. AB - Hemoglobin Beograd (B121 Glu-Val) is a rarely reported hemoglobin variant. It was first reported in Turkey in 1984. This report is a further observation of this variant in a 22-years old Turkish man. PMID- 27264084 TI - Autoimmune hemolytic anemia as a complication of primary biliary cirrhosis. AB - Primary biliary cirrhosis (PBC) is characterized by a continuous T-lymphocyte mediated attack on small intralobular bile ducts, with their gradual destruction. Patients with PBC often exhibit concomitant autoimmune conditions, and autoimmune hemolytic anemia (AIHA), that is idiopathic in 50% of cases, has rarely been associated to PBC. Ursodeoxycholic acid (UDCA) has been considered the main treatment to PBC patients through a decrease in the detergent effect of endogenous bile acids, concomitantly reducing the hemolytic process. We report the case of a female patient with AIHA complicating PBC, treated with short course prednisone and UDCA, with good response. PMID- 27264085 TI - Massive pericardial effusion and dilated cardiomyopathy in a patient with familial multiple myeloma. AB - An 80-years-old-man with adult polycystic kidney disease and familial multiple myeloma that is complicated with massive pericardial effusion and dilated cardiomyopathy during the course of the disease is presented. Although no definite single genetic disorder is described, multiple myeloma cases may be seen in certain families. Environmental factors are also blamed in the etiology. Multiple myeloma may be complicated by myocardial and pericardial involvement, diagnoses of which are possible only during postmortem examination in some cases. PMID- 27264086 TI - Images in Hematology. PMID- 27264087 TI - A Material Conferring Hemocompatibility. AB - There is a need for biomimetic materials for use in blood-contacting devices. Blood contacting surfaces maintain their patency through physico-chemical properties of a functional endothelium. A poly(carbonate-urea) urethane (PCU) is used as a base material to examine the feasibility of L-Arginine methyl ester (L AME) functionalized material for use in implants and coatings. The study hypothesizes that L-AME, incorporated into PCU, functions as a bioactive porogen, releasing upon contact with blood to interact with endothelial nitric oxide synthase (eNOS) present in blood. Endothelial progenitor cells (EPC) were successfully cultured on L-AME functionalized material, indicating that L-AME increases cell viability. L-AME functionalized material potentially has broad applications in blood-contacting medical devices, as well as various other applications requiring endogenous up-regulation of nitric oxide, such as wound healing. This study presents an in-vitro investigation to demonstrate the novel anti-thrombogenic properties of L-AME, when in solution and when present within a polyurethane-based polymer. PMID- 27264088 TI - Use of Transcranial Doppler Ultrasound for Diagnosis of Brain Death in Patients with Severe Cerebral Injury. AB - BACKGROUND The aim of this study was to investigate the use of transcranial Doppler (TCD) for diagnosis of brain death in patients with severe cerebral injury. MATERIAL AND METHODS This retrospective study enrolled 42 patients based on inclusion and exclusion criteria. All patients were divided into either the brain death group or the survival group according to prognosis. Blood flow of the brain was examined by TCD and analyzed for spectrum changes. The average blood flow velocity (Vm), pulse index (PI), and diastolic blood flow in reverse (RDF) were recorded and compared. RESULTS The data demonstrated that the average speed of bilateral middle cerebral artery blood flow in the brain death group was significantly reduced (P<0.05). However, the PI of the brain death group increased significantly. Moreover, RDF spectrum and nail-like sharp peak spectrum of the brain death group was higher than in the survival group. CONCLUSIONS Due to its simplicity, high repeatability, and specificity, TCD combined with other methods is highly valuable for diagnosis of brain death in patients with severe brain injury. PMID- 27264090 TI - Elevated Serum Retinol and Low Beta-Carotene but not Alpha-Tocopherol Concentrations Are Associated with Dyslipidemia in Brazilian Adolescents. AB - The purpose of this study was to investigate the status of retinol, beta carotene, and alpha-tocopherol serum concentrations in adolescents with dyslipidemia. A case series dyslipidemia study was conducted, with an attached control group, including 104 adolescents of public schools in Recife during the months of March/April 2013. Retinol, beta-carotene and alpha-tocopherol serum concentrations were analysed by high efficiency liquid chromatography. Sociodemographic, anthropometric, clinical and biochemical variables were analysed. Dyslipidemic adolescents had high serum concentrations of both retinol (p=0.007) and beta-carotene/apolipoprotein A-I ratio (p=0.034); they also had low concentrations of beta-carotene/total cholesterol (p<0.0001) and beta carotene/apolipoprotein B ratios (p=0.033) when compared to the controls. The alpha-tocopherol serum status was not associated with dyslipidemia. Overweight, abdominal obesity, lipid profile markers, and systolic and diastolic blood pressures were more prevalent in dyslipidemic adolescents. The findings show an association between vitamin A and dyslipidemia in adolescents. However, additional investigations of this risk group are necessary to clarify the mechanisms of action of this nutrient in the pathogenesis of this syndrome, aiming at reducing cardiometabolic risks as of earlier ages. PMID- 27264091 TI - Effects of Biotin Deficiency on Biotinylated Proteins and Biotin-Related Genes in the Rat Brain. AB - Biotin is a water-soluble vitamin that functions as a cofactor for biotin dependent carboxylases. The biochemical and physiological roles of biotin in brain regions have not yet been investigated sufficiently in vivo. Thus, in order to clarify the function of biotin in the brain, we herein examined biotin contents, biotinylated protein expression (e.g. holocarboxylases), and biotin related gene expression in the brain of biotin-deficient rats. Three-week-old male Wistar rats were divided into a control group, biotin-deficient group, and pair-fed group. Rats were fed experimental diets from 3 wk old for 8 wk, and the cortex, hippocampus, striatum, hypothalamus, and cerebellum were then collected. In the biotin-deficient group, the maintenance of total biotin and holocarboxylases, increases in the bound form of biotin and biotinidase activity, and the expression of an unknown biotinylated protein were observed in the cortex. In other regions, total and free biotin contents decreased, holocarboxylase expression was maintained, and bound biotin and biotinidase activity remained unchanged. Biotin-related gene (pyruvate carboxylase, sodium dependent multivitamin transporter, holocarboxylase synthetase, and biotinidase) expression in the cortex and hippocampus also remained unchanged among the dietary groups. These results suggest that biotin may be related to cortex functions by binding protein, and the effects of a biotin deficiency and the importance of biotin differ among the different brain regions. PMID- 27264089 TI - A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels. AB - The outer subventricular zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species such as human and ferret, where it contains abundant basal radial glia cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident downregulation of Cdh1 and Trnp1, and their upregulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease. PMID- 27264092 TI - Vitamin D Supplementation Causes a Decrease in Blood Cholesterol in Professional Rowers. AB - In the skin vitamin D3 is synthesized from cholesterol, which leaves the question whether a feedback mechanism controlling the level of blood cholesterol exists. Here we investigate the effects of vitamin D3 supplementation on serum lipids in professional rowers. The rowers were divided into two groups following the same training schedule for 4 wk: one received placebo (TP) while the second received 5,000 IU of vitamin D3 every day (TD3). Plasma total antioxidant status, total triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol (LDL-C) and 25 hydroxyvitamin D (25-OH-D3) were determined in pre- and post-intervention. The ratios of TC/HDL-C and LDL-C/HDL-C were also calculated. Furthermore, maximal oxygen uptake was also measured at baseline. There were significant decreases over time in the TD3 group in TC 186+/-18 vs 163+/-21 (p<0.05) and HDL-C; LDL-C also decreased, but the changes were not statistically significant. Moreover, the supplementation caused a significant rise in blood 25-OH-D3 (+98%). Neither training nor vitamin D3 supplementation had an effect on total antioxidant status. In conclusion, the alterations in the lipoprotein profile seen in this study would suggest that effects of regular exercise on lipoprotein profile may linked to vitamin D3 status. PMID- 27264093 TI - Diet-Induced Thermogenesis and Expression Levels of Thyroid Hormone Target Genes and Their Products in Rats Differ between Meat Proteins. AB - We compared the effects of purified meat proteins on postprandial thermogenesis and on the secretion of and responsiveness to thyroid hormones (THs) in rats. Body temperatures at 2 h after feeding were significantly higher in the chicken and mutton protein groups than in the other groups, and these proteins seem to have a strong thermogenic effect. There were no significant differences in plasma TH concentrations among the groups, but levels of TH-responsive Spot 14 protein in the liver and brown adipose tissue were significantly higher in the chicken and mutton protein groups than in the other groups. Levels of malic enzyme 1 protein in the liver and brown adipose tissue were significantly higher in the chicken protein group than in the other groups except for the mutton protein group. Furthermore, levels of uncoupling protein 1 were higher in the chicken and mutton protein groups than in the other groups. The results suggest that the difference in postprandial thermogenesis of meat is strongly dependent on meat proteins; chicken and mutton proteins are strong promoters of postprandial thermogenesis, and THs may contribute to this effect. Since strong postprandial thermogenesis and high expression levels of TH target genes and their products were not observed in the amino acid group, chicken and mutton proteins or their digested peptides might contribute to these effects. PMID- 27264094 TI - Relationship of Consumption of Meals Including Grain, Fish and Meat, and Vegetable Dishes to the Prevention of Nutrient Deficiency: The INTERMAP Toyama Study. AB - A Japanese-style diet consists of meals that include grain (shushoku), fish and meat (shusai), and vegetable dishes (fukusai). Little is known about the association of such meals (designated well-balanced meals hereafter) with nutrient intake. We therefore examined the frequency of well-balanced meals required to prevent nutrient deficiency. Participants were Japanese people, ages 40 to 59 y, from Toyama, recruited for INTERMAP, in an international population based study. Each person provided 4 in-depth 24-h dietary recalls (149 men, 150 women). The prevalence of risk ratios of not meeting the Dietary Reference Intakes for Japanese (2015) was calculated. Well-balanced diets were assessed by the Japanese Food Guide Spinning Top. We counted the frequencies of meals in which participants consumed 1.0 or more servings of all 3 dishes categories. We divided the frequency of consumption of well-balanced meals into the following 4 groups: <1.00 time/d, 1.00-1.49 times/d, 1.50-1.74 times/d, and >=1.75 times/d. Compared with participants in the highest frequency group for well-balanced meals, those who consumed well-balanced meals less than once a day had a higher risk of not meeting the adequate intake for potassium and the recommended dietary allowance for vitamin A. Those who consumed well-balanced meals on average less than 1.50 times per day had a higher risk of not meeting the recommended dietary allowance for calcium and vitamin C. Our results suggest that individuals should on average consume well-balanced meals more than 1.5 times per day to prevent calcium and vitamin C deficiencies. PMID- 27264095 TI - Comparison of Predicted Energy Expenditure in Japanese Patients with Non Alcoholic Fatty Liver Disease to Establish a Suitable Nutrition Intervention. AB - The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing in Western and Asian countries, including Japan. NAFLD includes the condition of non alcoholic steatohepatitis, which can progress to end-stage liver disease. Weight reduction based on basal energy expenditure (BEE) is considered to be the only established treatment for patients with NAFLD. However, a formula that is suitable for predicting BEE in Japanese patients with NAFLD remains to be determined. We enrolled 77 Japanese patients who were diagnosed with NAFLD according to histological findings. Their BEE was measured (mBEE) by indirect calorimetry. Physical findings, laboratory data and their predicted BEE (pBEE) values were compared with the mBEE values. All pBEE values were evaluated as a root mean squared error (RMSE) and an accurate estimation. The mBEE values correlated with the patient's weight, skeletal muscle mass, and age. Most of predictive formulae overestimated BEE in NAFLD patients in the present study. In contrast, the Kyoto equation provided an accurate prediction. Most prediction formulae included body weight as a reference of the skeletal muscle mass and were established using data from a healthy study population. However, differences in muscle mass exist among different races, and body composition differs between healthy individuals and those with high BMIs. The improved accuracy of the Kyoto equation is likely due to the similar backgrounds of the patients in the present study. The Kyoto equation is the most suitable formula for estimating BEE in Japanese patients with NAFLD. PMID- 27264096 TI - Prevalence of Inadequate Nutrient Intake in Japanese Community-Dwelling Older Adults Who Live Alone. AB - Dietary assessment of community-dwelling Japanese older adults who live alone using Dietary Reference Intakes (DRIs) is limited. The present study aimed to estimate the prevalence of inadequate nutrient intake among Japanese community dwelling older adults by sex and young-old and old-old population groups to identify the most vulnerable groups that need support. A cross-sectional survey was conducted from October 2012 to October 2013 with community-dwelling adults aged 65 y or older who lived alone. Participants were drawn from six cities in four Japanese prefectures. We used two days of dietary survey data to estimate participants' usual intake. The proportion of inadequate intake was assessed using the Estimated Average Requirement (EAR) cut-point method, Tolerable Upper Intake Level, and the tentative dietary goal for preventing life-style related diseases (DG) based on DRIs for Japanese, 2015. Data for 494 participants (162 male, 332 female) over 988 d were examined to assess nutrient intake. We calculated the proportion of inadequate intake between males and females and between young-old and old-old population groups (65-74 y and >=75 y) using chi square or Fisher's exact tests. For six nutrients, the estimated proportion of participants with a usual intake below EAR was higher in males than females. In addition, a higher estimated proportion of female participants was within the DG range for the percentage of energy from protein, fat, and carbohydrates, and had a usual intake of two nutrients above DG than males. Our findings showed that among Japanese older adults, males were more vulnerable in terms of inadequate nutrient intake compared with females. PMID- 27264097 TI - Strong Inhibition of Secretory Sphingomyelinase by Catechins, Particularly by (-) Epicatechin 3-O-Gallate and (-)-3'-O-Methylepigallocatechin 3-O-Gallate. AB - Sphingomyelinases (SMases) are key enzymes involved in many diseases which are caused by oxidative stress, such as atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease, and Alzheimer's disease. SMases hydrolyze sphingomyelin to generate ceramide, a well-known pro-apoptotic lipid. SMases are classified into five types based on pH optimum, subcellular localization, and cation dependence. Previously, we demonstrated that elevation of secretory sphingomyelinase (sSMase) activity increased the plasma ceramide concentration under oxidative stress induced by diabetes and atherosclerosis in murine models. These results suggest that sSMase inhibitors can prevent the progress of these diseases. The present study demonstrated that sSMase activity was activated by oxidation and inhibited by reduction. Furthermore, we examined whether catechins inhibited the sSMase activity in a physiological plasma concentration. Among catechins, (-)-epicatechin 3-O-gallate (ECg) exhibited strong inhibitory effect on sSMase (IC50=25.7 MUM). This effect was attenuated by methylation at the 3"- or 4"-position. On the other hand, (-)-epigallocatechin 3-O-gallate (EGCg) and ( )-catechin 3-O-gallate (Cg) exhibited weaker inhibitory activity than ECg, and ( )-epicatechin and (-)-epigallocatechin did not affect sSMase activity. Additionally, one synthetic catechin, (-)-3'-O-methylepigallocatechin 3-O-gallate (EGCg-3'-O-Me), showed the strongest inhibitory effect (IC50=1.7 MUM) on sSMase. This phenomenon was not observed for (-)-4'-O-methylepigallocatechin 3-O-gallate. These results suggest that the reduction potential, the presence of the galloyl residue at the C-3 position, and the steric requirement to interact with sSMase protein are important for effective inhibition of sSMase. PMID- 27264098 TI - The Biosynthesis of the Pyrimidine Moiety of Thiamin in Halobacterium salinarum. AB - The biosynthetic pathway of the pyrimidine moiety of thiamin was studied in the archaean Halobacterium salinarum. Thiamin is biosynthesized from 4-amino-5 hydroxymethyl-2-methylpyrimidine (pyrimidine) and 5-(2-hydroxyethyl)-4 methylthiazole (thiazole). The pyrimidine and the thiazole are biosynthesized de novo in microorganisms. The biosynthetic routes of pyrimidine in microorganisms differ between eukaryote and eubacteria. In the eukaryote Saccharomyces cerevisiae, histidine and pyridoxine are the precursors of pyrimidine, while in the eubacterium Escherichia coli, pyrimidine is biosynthesized from 5 aminoimidazole ribonucleotide (AIR), an intermediate of purine biosynthesis. Tracer investigations revealed that [(15)N]-, [1-(13)C]- and [2-(13)C] glycine, precursors of AIR, were incorporated into the pyrimidine in H. salinarum. These results suggested that the biosynthetic route of the pyrimidine in H. salinarum is similar to that of E. coli. PMID- 27264099 TI - Effect of Tea Catechins on Folate Analysis in Green Tea by Microbiological Assay. AB - Green tea is thought to be a primary source of folate in the Japanese diet, based on folate content analyzed by a microbiological assay. Green tea also contains high amount of catechins, in particular, epigallocatechin gallate (EGCg), which was demonstrated to be able to inhibit the digestive enzyme activities and microbial growth in the folate assay. In the present study, we examined whether tea catechins interfered with components of the folate assay for green tea. A marked inhibitory effect of EGCg on microbial growth was observed at an inhibitory concentration of higher than 10 MUg/mL. Tea catechins without the galloyl moiety did not show an inhibitory effect. EGCg inhibited the activity of the three enzymes used for assay sample preparation at an inhibitory concentration of higher than 750 MUg/mL for alpha-amylase, 1,000 MUg/mL for protease, and 50 MUg/mL for conjugase. However, with each step of the assay, the actual concentration of EGCg was decreased to below the inhibitory concentration of each analytical step. Lack of influence of EGCg on green tea folate assay was confirmed by an addition of folate standard in tea infusion. These results suggested that tea catechins have no practical impact on folate analysis in green tea, using the general microbiological assay. PMID- 27264100 TI - Errata. PMID- 27264101 TI - HLA Profile of Celiac Disease among First-Degree Relatives from a Tertiary Care Center in North India. AB - OBJECTIVE: To study the prevalence of Celiac disease (CD) in first-degree relatives (FDR) of CD children. METHODS: This observational study was performed in FDR (parents and siblings) of consecutive newly diagnosed cases of CD enrolled from January 2011 through March 2012. Screening for CD in FDR was done using IgA tissue transglutaminase (tTG) levels in serum and the seropositive subset underwent upper gastrointestinal (UGI) endoscopy and biopsy to confirm the disease. In addition, HLA analysis for CD was performed in most of the index cases and FDR. RESULTS: Of 202 FDR of the 64 index cases with CD, 17.3 % (35/202) were seropositive for IgA tTG while confirmed biopsy proven CD was diagnosed in 10.2 % (8/78) of children and 8.1 % (10/124) of adults. HLA DQ2/DQ8 was positive in 96.7 % of the index cases and all FDR with confirmed CD. CONCLUSIONS: The prevalence of CD among FDR is 9 fold higher than the general population. High prevalence of CD in presence of anemia and short stature in seropositive FDR in index study indicates need of targeted screening of this subgroup for the presence of CD.CD is unlikely in the absence of HLADQ2/DQ8. PMID- 27264102 TI - Insights into the unexpected chemoselectivity in Bronsted acid catalyzed cyclization of isatins with enaminones: convenient synthesis of pyrrolo[3,4 c]quinolin-1-ones and spirooxindoles. AB - Divergent cascade syntheses constitute a highly attractive and challenging area in synthetic chemistry, and can exhibit unexpected chemoselectivity. Herein, a Bronsted acid-controlled protocol is described for the efficient catalysis of two different reactions, namely acylation cascade- and [1+2+3]-type cyclization of enaminones and isatins for the concise synthesis of highly functionalized pyrrolo[3,4-c]quinolin-1-ones and spirooxindoles in the presence of carboxylic acids and KHSO4, respectively. The observed chemoselectivity was reasonably explained by trapping the intermediate alpha,beta-unsaturated 2-oxindoles, and the source of the hydroxyl group, carbocation intermediate, and amination reaction were also evaluated. PMID- 27264103 TI - Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFalpha. AB - Rhomboid intramembrane proteases are the enzymes that release active epidermal growth factor receptor (EGFR) ligands in Drosophila and C. elegans, but little is known about their functions in mammals. Here we show that the mammalian rhomboid protease RHBDL4 (also known as Rhbdd1) promotes trafficking of several membrane proteins, including the EGFR ligand TGFalpha, from the endoplasmic reticulum (ER) to the Golgi apparatus, thereby triggering their secretion by extracellular microvesicles. Our data also demonstrate that RHBDL4-dependent trafficking control is regulated by G-protein coupled receptors, suggesting a role for this rhomboid protease in pathological conditions, including EGFR signaling. We propose that RHBDL4 reorganizes trafficking events within the early secretory pathway in response to GPCR signaling. Our work identifies RHBDL4 as a rheostat that tunes secretion dynamics and abundance of specific membrane protein cargoes. PMID- 27264105 TI - Critical behavior in a stochastic model of vector mediated epidemics. AB - The extreme vulnerability of humans to new and old pathogens is constantly highlighted by unbound outbreaks of epidemics. This vulnerability is both direct, producing illness in humans (dengue, malaria), and also indirect, affecting its supplies (bird and swine flu, Pierce disease, and olive quick decline syndrome). In most cases, the pathogens responsible for an illness spread through vectors. In general, disease evolution may be an uncontrollable propagation or a transient outbreak with limited diffusion. This depends on the physiological parameters of hosts and vectors (susceptibility to the illness, virulence, chronicity of the disease, lifetime of the vectors, etc.). In this perspective and with these motivations, we analyzed a stochastic lattice model able to capture the critical behavior of such epidemics over a limited time horizon and with a finite amount of resources. The model exhibits a critical line of transition that separates spreading and non-spreading phases. The critical line is studied with new analytical methods and direct simulations. Critical exponents are found to be the same as those of dynamical percolation. PMID- 27264106 TI - Tensional acoustomechanical soft metamaterials. AB - We create acoustomechanical soft metamaterials whose response to uniaxial tensile stressing can be easily tailored by programming acoustic wave inputs, resulting in force versus stretch curves that exhibit distinct monotonic, s-shape, plateau and non-monotonic snapping behaviors. We theoretically demonstrate this unique metamaterial by considering a thin soft material sheet impinged by two counter propagating ultrasonic wave inputs across its thickness and stretched by an in plane uniaxial tensile force. We establish a theoretical acoustomechanical model to describe the programmable mechanics of such soft metamaterial, and introduce the first- and second-order tangential stiffness of its force versus stretch curve to boundary different behaviors that appear during deformation. The proposed phase diagrams for the underlying nonlinear mechanics show promising prospects for designing tunable and switchable photonic/phononic crystals and microfluidic devices that harness snap-through instability. PMID- 27264104 TI - Nanodisc-cell fusion: control of fusion pore nucleation and lifetimes by SNARE protein transmembrane domains. AB - The initial, nanometer-sized connection between the plasma membrane and a hormone or neurotransmitter-filled vesicle -the fusion pore- can flicker open and closed repeatedly before dilating or resealing irreversibly. Pore dynamics determine release and vesicle recycling kinetics, but pore properties are poorly known because biochemically defined single-pore assays are lacking. We isolated single flickering pores connecting v-SNARE-reconstituted nanodiscs to cells ectopically expressing cognate, "flipped" t-SNAREs. Conductance through single, voltage clamped fusion pores directly reported sub-millisecond pore dynamics. Pore currents fluctuated, transiently returned to baseline multiple times, and disappeared ~6 s after initial opening, as if the fusion pore fluctuated in size, flickered, and resealed. We found that interactions between v- and t-SNARE transmembrane domains (TMDs) promote, but are not essential for pore nucleation. Surprisingly, TMD modifications designed to disrupt v- and t-SNARE TMD zippering prolonged pore lifetimes dramatically. We propose that the post-fusion geometry of the proteins contribute to pore stability. PMID- 27264107 TI - Genome-wide DNA methylation profiles changes associated with constant heat stress in pigs as measured by bisulfite sequencing. AB - Heat stress affects muscle development and meat quality in food animals; however, little is known regarding its regulatory mechanisms at the epigenetic level, such as via DNA methylation. In this study, we aimed to compare the DNA methylation profiles between control and heat-stressed pigs to identify candidate genes for skeletal muscle development and meat quality. Whole-genome bisulfite sequencing was used to investigate the genome-wide DNA methylation patterns in the longissimus dorsi muscles of the pigs. Both groups showed similar proportions of methylation at CpG sites but exhibited different proportions at non-CpG sites. A total of 57,147 differentially methylated regions were identified between the two groups, which corresponded to 1,422 differentially methylated genes. Gene ontogeny and KEGG pathway analyses indicated that these were mainly involved in energy and lipid metabolism, cellular defense and stress responses, and calcium signaling pathways. This study revealed the global DNA methylation pattern of pig muscle between normal and heat stress conditions. The result of this study might contribute to a better understanding of epigenetic regulation in pig muscle development and meat quality. PMID- 27264108 TI - The alterations in the extracellular matrix composition guide the repair of damaged liver tissue. AB - While the cellular mechanisms of liver regeneration have been thoroughly studied, the role of extracellular matrix (ECM) in liver regeneration is still poorly understood. We utilized a proteomics-based approach to identify the shifts in ECM composition after CCl4 or DDC treatment and studied their effect on the proliferation of liver cells by combining biophysical and cell culture methods. We identified notable alterations in the ECM structural components (eg collagens I, IV, V, fibronectin, elastin) as well as in non-structural proteins (eg olfactomedin-4, thrombospondin-4, armadillo repeat-containing x-linked protein 2 (Armcx2)). Comparable alterations in ECM composition were seen in damaged human livers. The increase in collagen content and decrease in elastic fibers resulted in rearrangement and increased stiffness of damaged liver ECM. Interestingly, the alterations in ECM components were nonhomogenous and differed between periportal and pericentral areas and thus our experiments demonstrated the differential ability of selected ECM components to regulate the proliferation of hepatocytes and biliary cells. We define for the first time the alterations in the ECM composition of livers recovering from damage and present functional evidence for a coordinated ECM remodelling that ensures an efficient restoration of liver tissue. PMID- 27264109 TI - Metabolic rates of giant pandas inform conservation strategies. AB - The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction. PMID- 27264110 TI - Integrated Acoustic Separation, Enrichment, and Microchip Polymerase Chain Reaction Detection of Bacteria from Blood for Rapid Sepsis Diagnostics. AB - This paper describes an integrated microsystem for rapid separation, enrichment, and detection of bacteria from blood, addressing the unmet clinical need for rapid sepsis diagnostics. The blood sample is first processed in an acoustophoresis chip, where red blood cells are focused to the center of the channel by an acoustic standing wave and sequentially removed. The bacteria containing plasma proceeds to a glass capillary with a localized acoustic standing wave field where the bacteria are trapped onto suspended polystyrene particles. The trapped bacteria are subsequently washed while held in the acoustic trap and released into a polymer microchip containing dried polymerase chain reaction (PCR) reagents, followed by thermocycling for target sequence amplification. The entire process is completed in less than 2 h. Testing with Pseudomonas putida spiked into whole blood revealed a detection limit of 1000 bacteria/mL for this first-generation analysis system. In samples from septic patients, the system was able to detect Escherichia coli in half of the cases identified by blood culture. This indicates that the current system detects bacteria in patient samples in the upper part of the of clinically relevant bacteria concentration range and that a further developed acoustic sample preparation system may open the door for a new and faster automated method to diagnose sepsis. PMID- 27264111 TI - Optimizing the Interactions of Surfactants with Graphitic Surfaces and Clathrate Hydrates. AB - Surfactants are amphiphilic molecules active at the surface/interface and able to self-assemble. Because of these properties, surfactants have been extensively used as detergents, emulsifiers, foaming agents, and wetting agents. New perspectives have been opened by the exploitation of surfactants for their capacity to interact as well with simple molecules or surfaces. This feature article gives an overview of significant contributions in the panorama of the current research on surfactants, partly accomplished as well by our research group. We look at several recent applications (e.g., adsorption to graphitic surfaces and interactions with hydrate crystals) with the eye of physical organic chemists. We demonstrate that, from the detailed investigation of the forces involved in the interactions with hydrophobic surfaces, it is possible to optimize the design of the surfactant that is able to form a stable and unbundled carbon nanotube dispersion as well as the best exfoliating agent for graphitic surfaces. By studying the effect of different surfactants on the capacity to favor or disfavor the formation of a gas hydrate, it is possible to highlight the main features that a surfactant should possess in order to be devoted to that specific application. PMID- 27264112 TI - Click and Patterned Functionalization of Graphene by Diels-Alder Reaction. AB - Chemical functionalization is a promising approach to controllably manipulate the characteristics of graphene. Here, we designed cis-dienes, featuring two dihydronaphthalene backbones, to decorate a graphene surface via Diels-Alder (DA) click reaction. The installation of a diene moiety into a nonplanar molecular structure to form cis-conformation enables a rapid (~5 min) DA reaction between graphene and diene groups. Patterned graphene of sub-micrometer resolution can be obtained by easily soaking poly(methyl methacrylate)-masked graphene in solution of hydroxyl-substituted cis-diene at room temperature. The functionalization degree can be further controlled by carrying out the reaction at higher temperature. The present result gives important insight into the effect of molecular conformation on the graphene functionalization process, and provides an effective and facile method for graphene functionalization. PMID- 27264113 TI - Is it time to abandon the digital rectal examination? Lessons from the PLCO Cancer Screening Trial and peer-reviewed literature. AB - OBJECTIVE: In 2012 the US Preventive Services Task Force released recommendations against prostate specific antigen (PSA) based screening for prostate cancer, but did not fully address screening via digital rectal exam (DRE). As such, many practitioners continue to perform DRE in attempts to identify men with clinically significant prostate cancer (CSPC). This study seeks to determine the value of DRE in detecting CSPC in the era of PSA-based screening. METHODS: Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial, a nationwide population-based study evaluating cancer screening programs and their impact on cancer mortality, was analyzed for PSA, DRE, and cancer status. In the screening arm of the PLCO, 38,340 men received annual PSA and DRE examinations for the first 3 years. Those with an abnormal test result were referred to their individual care provider for biopsy. The ability of DRE to detect CSPC, defined as intermediate risk or higher based on National Comprehensive Cancer Network guidelines and age <=75, was evaluated in the context of both normal and abnormal PSA. RESULTS: A total of 5064 men had abnormal DRE in the setting of normal PSA, of whom 99 (2%) were diagnosed with CSPC. When both PSA and DRE were abnormal, 218 (20%) participants were diagnosed with CSPC (RR = 2.06 [1.78-2.39] versus abnormal PSA alone). CONCLUSIONS: DRE screening in the setting of normal PSA captured an additional 2% of men with CSPC. This incremental gain suggests that routine DRE screening subjects a large number of men to invasive, potentially uncomfortable examinations for relatively minimal gain. KEY LIMITATIONS: Our conclusions are based on data derived from the PLCO study which has been criticized on the basis of inconsistent biopsies following positive screening tests, lack of end of study biopsies to determine population disease burden, and low numbers of black men. PMID- 27264119 TI - "I never thought that it would happen ... " Experiences of HIV seroconverters among HIV-discordant partnerships in a prospective HIV prevention study in Kenya. AB - In spite of access to behavioral and biomedical HIV prevention strategies, HIV transmission occurs. For HIV-serodiscordant couples, prevention programs can be tailored to address individual and couples' needs to preserve their relationship while minimizing HIV risk. Programs for serodiscordant couples may benefit from learning from experiences of couples who transmit HIV. We conducted 20 individual in-depth interviews with 10 initially HIV-serodiscordant couples who transmitted HIV during prospective follow-up at a peri-urban research site in Thika, Kenya. Data were analyzed inductively to identify situations that led to prevention failure and coping mechanisms. Inconsistent condom use driven by low HIV risk perception and alcohol use often preceded seroconversion while persistent blame frequently hindered couples' communication soon after seroconversion. In this emerging era of antiretroviral-based HIV prevention, couples' counseling can capitalize on opportunities to foster a supportive environment to discuss initiation and adherence to time-limited pre-exposure prophylaxis and lifelong antiretroviral therapy, in addition to strategies to reduce alcohol use, diffuse blame, and use condoms. PMID- 27264122 TI - Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review. AB - Despite substantial advancement in the understanding and treatment of chronic lymphocytic leukemia (CLL), a standard curative approach does not exist. The choice of treatment is generally based on the existence of biological and genetic factors associated with the prediction of prognosis, individual response to therapy, and duration of remission. About 20% of patients that require treatment have an aggressive disease course and die within a few years, despite early initiation of intensive therapy (poor-risk CLL). Poor-risk CLL can be predicted by the presence of genomic markers, and the quality and duration of response to purine-analogue-based treatment. Within this patient subgroup alternative treatment approaches such as alemtuzumab or new substances such as flavopiridol or IMiDs(r) should be considered. To date, the only treatment bearing curative potential is allogeneic stem cell transplantation; in contrast to conventional immunochemotherapy, it can provide long-term disease control, even in patients with del 17p or other unfavorable biological and clinical risk factors. The aim of this review was to outline the current strategies for the diagnosis and management of CLL, with a focus on high-risk CLL. PMID- 27264120 TI - Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years. AB - BACKGROUND: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence. METHODS: We conducted a double-blind, placebo controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival. RESULTS: We enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5 year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P=0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P=0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P=0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life. CONCLUSIONS: The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.). PMID- 27264121 TI - Parkinson's disease and the Stroop color word test: processing speed and interference algorithms. AB - OBJECTIVE: Processing speed alters the traditional Stroop calculations of interference. Consequently, alternative algorithms for calculating Stroop interference have been introduced to control for processing speed, and have done so in a multiple sclerosis sample. This study examined how these processing speed correction algorithms change interference scores for individuals with idiopathic Parkinson's disease (PD, n = 58) and non-PD peers (n = 68). METHOD: Linear regressions controlling for demographics predicted group (PD vs. non-PD) differences for Jensen's, Golden's, relative, ratio, and residualized interference scores. To examine convergent and divergent validity, interference scores were correlated with standardized measures of processing speed and executive function. RESULTS: PD-non-PD differences were found for Jensen's interference score, but not Golden's score, or the relative, ratio, and residualized interference scores. Jensen's score correlated significantly with standardized processing speed but not executive function measures. Relative, ratio, and residualized scores correlated with executive function but not processing speed measures. Golden's score did not correlate with any other standardized measures. CONCLUSIONS: The relative, ratio, and residualized scores were comparable for measuring Stroop interference in processing speed-impaired populations. Overall, the ratio interference score may be the most useful calculation method to control for processing speed in this population. PMID- 27264123 TI - ABL gene kinase domain mutation scanning by denaturing high performance liquid chromatography sequencing method. AB - OBJECTIVE: Despite the efficacy of the BCR-ABL tyrosine kinase inhibitor imatinib, the development of resistance against imatinib has been observed. The most important mechanisms known to cause resistance are point mutations in the ABL tyrosine kinase and the ATP domain. This study describes the use of denaturing high performance liquid chromatography (dHPLC) as a method to screen for mutations of the ABL gene. METHODS: We used the dHPLC based assay for the screening of ABL point mutations. Forty chronic myeloid leukemia (CML) patients who showed resistance to imatinib were screened in parallel by dHPLC and direct sequencing. RESULTS: Nine of the 40 patients (23%) had mutations. CONCLUSION: dHPLC can be a useful method for pre-screening. Analyzing the mutations and monitoring (high-risk) patients can improve their prognosis and survival rate. dHPLC can potentially become a valuable tool for regular testing of patients in the future. PMID- 27264124 TI - Fluorescence in situ hybridization analysis of the hTERC region in acute myeloid leukemia patients. AB - OBJECTIVE: The telomerase RNA component (hTERC) gene is located at 3q26. Increased hTERC gene expression has been frequently observed and amplification was shown using fluorescence in situ hybridization (FISH) in different cancers. The aim of this study was to determine whether hTERC gene amplification is detectable by FISH in acute myeloid leukemia (AML) cells. METHODS: FISH and karyotype results at the time of diagnosis of 23 adult AML patients were retrospectively evaluated. Additionally, fixed cells were hybridized with an hTERC region-specific FISH probe to determine gene amplification. RESULTS: Ten of the 23 patients had a normal karyotype and 6 had an abnormal karyotype. hTERC region amplification was not observed in any of the patients. CONCLUSION: Although it was reported that hTERC gene amplification may partially contribute to increased telomerase expression and activity in leukemic cells, it is not possible to make such a conclusion based on the results of the this study, as hTERC amplification was not observed in the study group. This suggests that increased telomerase activity via gene amplification in the development of AML may not be as important a factor as it is in solid tumors. PMID- 27264125 TI - Nitric oxide in gingival crevicular fluid and nitric oxide synthase expression in the gingiva of patients with sickle cell disease. AB - OBJECTIVE: This study aimed to biochemically measure the production of nitric oxide in gingival crevicular fluid and immunohistochemically measure the expression of inducible nitric oxide synthase in the gingiva of patients with sickle cell disease. Additionally, we aimed to obtain insight into the immunopathology of sickle cell disease by comparing inducible nitric oxide synthase levels in patients with sickle cell disease and controls using gingiva and gingival crevicular fluid. METHODS: The study included 20 sickle cell disease patients and 20 healthy controls. Immunohistochemical analysis was used to measure inducible nitric oxide synthase expression in gingiva and nitric oxide levels in gingival crevicular fluid were spectrophotometrically measured. RESULTS: Nitric oxide levels in the patients and controls did not differ significantly (21.2+/-4.5 and 23.1+/-2.3 MUM L-1, respectively, p>0.05). There weren't any statistically significant differences in infiltrated inflammatory cells, density of inflammatory cells that stained with inducible nitric oxide synthase, or nitric oxide expression in gingiva between the patient and control groups (p>0.05). CONCLUSION: To the best of our knowledge this is the first study to examine the expression of inducible nitric oxide synthase in the gingiva and gingival crevicular fluid in patients with sickle cell disease. Using the gingiva and gingival crevicular fluid we were unable to observe sickle cell disease associated inducible nitric oxide synthase expression and a difference in nitric oxide levels. PMID- 27264126 TI - The frequency of A91V in the perforin gene and the effect of tumor necrosis factor-alpha promoter polymorphism on acquired hemophagocytic lymphohistiocytosis. AB - OBJECTIVE: Numerous acquired etiological factors, such as infections, malignancies, and collagen tissue disorders, are involved in the development of acquired hemophagocytic lymphohistiocytosis (AHLH). Not everyone with the same etiological factors developments AHLH, which suggests the role of additional genetic or environmental predisposing factors that remain to be identified. METHODS: Perforin gene A91V missense transition (C>T change at position 272 in exon 2 of the perforin gene) and TNF-alpha gene promoter-1031 T>C nucleotide substitution are 2 candidate genetic predisposing factors due to their potential to alter inflammatory responses. In the present study these changes were investigated in healthy controls and AHLH patients. RESULTS: A91V transition was observed in 7 of the 159 (4.4%) controls. Among the 44 AHLH patients, 5 (11.3%) were heterozygous and the difference in the frequency of A91V transition, although striking (odds ratio: 2.8), was not statistically significant (p=0.09). All A91V-positive patients had infection. TNF-alpha-1031 T>C polymorphism was examined in 164 healthy controls and 40 AHLH patients, and the CC risk-elevating genotype was noted in 7 (4.3%) of the controls and 1 (2.5%) of the AHLH patients. The frequency of C and T alleles was 22.5% (n=18) and 77.5% (n=62) among the AHLH patients, and 22% (n=72) and 78% (n=259) among the controls, respectively. There wasn't a statistically significant difference between the groups in terms of allele frequencies (p>0.05). CONCLUSION: The present results indicate that compared to controls, A91V mutation was 2.8-fold more prevalent (according to the odds ratio) in the AHLH patients. A91V mutation is not uncommon in the general population and increases the risk of AHLH in patients with an underlying condition, especially those with an underlying infection. PMID- 27264127 TI - Acquired methemoglobinemia in infants. AB - OBJECTIVE: This study aimed to determine the etiologic factors of acquired methemoglobinemia in infants younger than three months in our region. METHODS: This study was carried out retrospectively in infants with methemoglobinemia admitted to Karadeniz Technical University, Pediatric Clinic, during the period 2000-2009. Infants with methemoglobinemia were identified according to the medical records or ICD-10 code. RESULTS: Nine infants with acquired methemoglobinemia (8 male, 1 female) were included in the study. Seven cases were associated with the use of prilocaine for circumcision, one case with the use of prilocaine-lidocaine for local pain therapy, and one case with neonatal sepsis caused by Staphylococcus aureus. CONCLUSION: Prilocaine should not be used in infants less than three months of age because of the risk of methemoglobinemia. Ascorbic acid is an effective therapy if methylene blue is not obtained. It should not be forgotten that sepsis caused by S. aureus may cause methemoglobinemia in infants. PMID- 27264128 TI - Splenic artery embolization: An alternative approach in a critically ill patient with autoimmune hemolytic anemia. AB - Assessment of general health status and hematological parameters usually precedes the use of invasive diagnostic and therapeutic procedures in critically ill patients. Angiography can be effective and safe as a substitute for major surgical procedures, or as a bridging therapy in such cases. We present a critically ill patient with hemolytic anemia that underwent splenic artery embolization as a bridging therapy. We aimed to emphasize that minimally invasive approaches and multidisciplinary care can be utilized in the treatment of critically ill patients with accompanying hematological disease. PMID- 27264129 TI - Wiskott-Aldrich syndrome mutation in two Turkish siblings with X-linked thrombocytopenia. AB - Wiskott-Aldrich syndrome (WAS) is a clinical condition characterized by thrombocytopenia, eczema, and life-threatening infections. In some cases autoimmunity-related problems and even malignancy might be seen; however, some patients have milder clinical manifestations due to mutations in the same gene family, such as in X-linked thrombocytopenia (XLT), which is generally not associated with serious symptoms of disease, except for thrombocytopenia. Herein we report 2 siblings with chronic thrombocytopenia that were diagnosed with XLT based on a missense mutation in the WASP gene (223G>A, Val75Met). To the best of our knowledge this mutation has not been previously reported in a Turkish patient with XLT. PMID- 27264130 TI - Are cup-like blasts specific to AML patients with FLT3 ITD and a normal karyotype? An ALL case report and review of the literature. AB - Cup-like morphology is defined as cup-like nuclear invagination spanning >=25% of the nuclear diameter in >10% of blasts. Studies have shown that FLT3 ITD and normal cytology are strongly associated with cup-like morphology in acute myeloid leukemia (AML) patients. Herein we describe a patient with cup-like blasts that was diagnosed and treated for common acute lymphoblastic leukemia (ALL). In contrast to the literature, the presented case was Philadelphia chromosome positive and FLT3 ITD negative. PMID- 27264131 TI - Central retinal artery occlusion as the presenting sign of essential thrombocythemia. PMID- 27264132 TI - "Arbitrary" criterion for the diagnosis of acute leukemia. PMID- 27264133 TI - Paclitaxel therapy and immune thrombocytopenic purpura: Coincidence or association? PMID- 27264134 TI - Interaction between hereditary spherocytosis and the beta-thalassemia trait: A case report. PMID- 27264135 TI - Hematogones in the bone marrow of a child with Rubella virus-associated immune thrombocytopenic purpura concomitant with iron deficiency anemia. PMID- 27264136 TI - Multiple myeloma with multilobated plasma cell nuclei. PMID- 27264138 TI - Treatment of Dravet Syndrome. AB - Dravet syndrome is among the most challenging electroclinical syndromes. There is a high likelihood of recurrent status epilepticus; seizures are medically refractory; and patients have multiple co-morbidities, including intellectual disability, behaviour and sleep problems, and crouch gait. Additionally, they are at significant risk of sudden unexplained death. This review will focus predominantly on the prophylactic medical management of seizures, addressing both first-line therapies (valproate and clobazam) as well as second-line (stiripentol, topiramate, ketogenic diet) or later options (levetiracetam, bromides, vagus nerve stimulation). Sodium channel agents-including carbamazepine, oxcarbazepine, phenytoin and lamotrigine-should be avoided, as they typically exacerbate seizures. Several agents in development may show promise, specifically fenfluramine and cannabidiol, but they need further evaluation in randomized, controlled trials. In addition to prophylactic treatment, all patients need home-rescue medication and a status epilepticus protocol that can be carried out in their local hospital. Families must be counselled on non-pharmacologic strategies to reduce seizure risk, including avoidance of triggers that commonly induce seizures (including hyperthermia, flashing lights and patterns). In addition to addressing seizures, holistic care for a patient with Dravet syndrome must involve a multidisciplinary team that includes specialists in physical, occupational and speech therapy, neuropsychology, social work and physical medicine. PMID- 27264137 TI - Ovarian malignancy unmasked by venous gangrene in a patient on warfarin therapy: a case report. AB - BACKGROUND: Venous gangrene complicating deep vein thrombosis in the context of anticoagulation use in patients with gynecologic malignancy is rarely reported. We report an unusual presentation of venous gangrene of the lower limbs associated with warfarin therapy in a 53-year-old woman from the Cook Islands with an occult ovarian cancer. CASE PRESENTATION: A 53-year-old woman of Cook Islands origin presented with exertional dyspnea, rapid atrial fibrillation, bilateral lower limb edema, and painful digital ischemia of her hallux. She was on warfarin therapy for atrial fibrillation and had a stable therapeutic international normalized ratio. Bilateral proximal lower limb deep vein thrombosis and digital gangrene subsequently developed in the setting of a supratherapeutic international normalized ratio and platelet count depletion. Her warfarin was reversed and heparin therapy was commenced with resulting correction of her thrombocytopenia. CONCLUSIONS: We would like to attract the attention of the reader to the potential hazard of the use of warfarin in patients with malignancy. In our case, we also demonstrated a predictive value of supratherapeutic international normalized ratio and platelet count depletion that could herald massive thrombosis and gangrene in a patient who was previously stable on warfarin therapy. Early recognition and prompt reversal of warfarin in these circumstances is essential to correct the unbalanced prothrombotic process that leads to extensive thrombosis and gangrene. The outlook of such cases remains dismal and results in extensive morbidity and mortality. PMID- 27264139 TI - Dravet Syndrome: Diagnosis and Long-Term Course. AB - Dravet syndrome is one of the most severe epilepsy syndromes of early childhood, and it comes with very high morbidity and mortality. The typical presentation is characterized by hemiclonic or generalized clonic seizures triggered by fever during the first year of life, followed by myoclonic, absence, focal and generalized tonic-clonic seizures. Non-convulsive status epilepticus and epileptic encephalopathy are common. Development is normal in the first year of life, but most individuals eventually suffer from intellectual impairment. Dravet syndrome is associated with mutations in the sodium channel alpha1 subunit gene (SCN1A) in 70-80% of individuals. SCN1A mutation results in inhibition of the GABAergic inhibitory interneurons, leading to excessive neuronal excitation. The "interneuron hypothesis" is the current most accepted pathophysiological mechanism of Dravet syndrome. The mortality rate is increased significantly in Dravet syndrome. Ataxia, a characteristic crouched gait and Parkinson's symptoms may develop in some individuals. It is likely that Dravet syndrome is underdiagnosed in adults with treatment-resistant epilepsy. Early diagnosis is important to avoid anti-seizure medications that exacerbate seizures. PMID- 27264140 TI - Helping Families Cope with the Severe Stress of Dravet Syndrome. AB - A child with Dravet syndrome shakes family life to the core. Dravet syndrome usually has three phases: (1) up to 1-11/2 years: with episodes of febrile status epilepticus but normal development; (2) age 11/2 to ~6-10 years: with frequent seizures of varying types, developmental stagnation, behavioural and sleep problems; (3) after ~10 years: improvement in seizures, deteriorating gait, intellectual disability but some developmental gains. Complete seizure control is rare-simply prescribing medication is inadequate to help families. Based on structured interviews with 24 families and confirmed by more informal discussions with other families, we suggest strategies for coping with this catastrophe. A child with Dravet syndrome usually means that one parent cannot work-financial pressures should be anticipated. In Stage 1, the approach to status should include a written protocol. An indwelling catheter for rapid venous access may be helpful. In Stage 2, assistance finding qualified babysitters is required, and the extended family needs encouragement to help. Appropriate equipment, rescue medication and protocols should travel with the child. Siblings may benefit from a system of one parent "on call." An internet support group provides an invaluable lifeline. In Stage 3, family isolation may be extreme-respite care and personal time for parents are important. Death from status, accidents and SUDEP (sudden unexplained death in epilepsy) occurs in 15%. Fear of SUDEP needs to be addressed. Moving from paediatric to adult care is frightening; an epilepsy transition clinic is useful. Attention to these realities may improve the quality of life for both child and family. PMID- 27264141 TI - Alternative treatment for hot flashes. PMID- 27264143 TI - Red cell glucose-6-phosphate dehydrogenase deficiency in Turkey. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocyte enzyme deficiency in the world. The epidemiological, biochemical and molecular studies on G6PD enzyme deficiency performed over the past 50 years are summarized herein, with special emphasis on the findings of studies related to the enzyme deficiency in Turkey. PMID- 27264144 TI - Malaria parasitemia and antimalaria prophylaxis in sickle cell anemia patients in steady staten. AB - Malaria parasitemia was assessed in 37 known sickle cell anemia patients attending the routine hematological clinic of the University of Benin Teaching Hospital, Benin-City, Edo State. Parasitemia was determined using the quantitative buffy coat analysis. The prevalence of malaria parasitemia among the population studied was 86.5%. There was no significant difference in the prevalence of parasitemia among the male and female sicklers (p=0.35). Malaria parasitemia was significantly associated with hematocrit <0.20 (p=0.03). There was no statistically significant difference between the type of prophylaxis used and parasitemia. In conclusion, the role of malaria prophylaxis in preventing parasitemia seems negligible. It is therefore recommended that more emphasis. PMID- 27264142 TI - An HBV-tolerant immunocompetent model that effectively simulates chronic hepatitis B virus infection in mice. AB - Hepatitis B virus (HBV) is the leading cause of liver disease and hepatic carcinoma (HCC). Approximately 350 million people worldwide are infected with HBV and at risk of chronicity. An efficient HBV-tolerant murine model that mimics HBV infection in humans is desirable for HBV-related research. In this study, we investigated and established a murine model by hydrodynamic injection (HDI) of pAAV/HBV into the tail vein of AAVS1 site element-transgenic mice. In 80% of the injected mice, the serum level of HBsAg reached 103-4 IU/ml and persisted for more than half a year. Next, the model was used to evaluate RNA interference (RNAi)-based antiviral therapy. Data obtained using the model demonstrated that this model will facilitate the elucidation of the mechanisms underlying chronic HBV infection and will also be useful for evaluating new antiviral drugs. PMID- 27264145 TI - Hematological profile of HIV patients in relation to immune status - a hospital based cohort from Varanasi, North India. AB - OBJECTIVES: To study the spectrum of hematological manifestations and evaluate the relationship between various hematological manifestations and CD4 cell counts in a hospital-based cohort of HIV-infected adults in and around Varanasi, North India. MATERIALS-METHODS: The clinical and hematological profiles of the patients attending the Infectious Disease Clinic, Varanasi, India were recorded. The relationship between CD4 counts and various hematological manifestations was analyzed. RESULTS: A total of 470 HIV-infected individuals were followed for 830 person years of observation (PYO). Rate of hematological episodes was 1047 episodes per 1000 PYO. CD4 counts were significantly lower in individuals with severe anemia and neutropenia compared to those without. However, no relation could be established between thrombocytopenia and CD4 counts. In the above- mentioned population, CD4 levels were significantly lower in those with anemia/neutropenia harboring any particular disease compared to those who had the same disease without anemia/ neutropenia. CONCLUSIONS: There is a strong negative association between CD4 counts and the severity of anemia and neutropenia in this population. They can be considered as good clinical indicators to predict and access the underlying immune status. Though fall in the CD4 levels during neutropenia is observed, it is difficult to comment since the estimations of CD4 rely on the total leukocyte counts. However, the relation between anemia and disease progression is straight forward and quite useful for the treating physician. PMID- 27264146 TI - Cloning of chimerical translocations as positive control for molecular genetic diagnosis of leukemia. AB - The diagnosis of leukemia-specific mRNAs by polymerase chain reaction (PCR) and reverse transcription-PCR (RT-PCR) require well-known positive standard controls. In general, the positive controls are obtained from cell lines and leukemia patients who have been diagnosed at the molecular level by RT-PCR. These are expensive and restricted sources for standard positive controls. Thus, there is a need for less expensive and reproducible standard positive controls in this area. We have cloned the t (9: 22) p190, t (9: 22) p210, t (4: 11), t (1: 19), t (15: 17), t (12; 21) breakpoint junctions of fusion genes into the plasmids. Cloned fusion genes are suitable for testing PCR experiments of the molecular genetic diagnosis of leukemia samples. We cloned and optimized fusion gene junctions as a standard positive control to check PCR efficiency and as a standard positive marker for diagnosis. PMID- 27264147 TI - T-helper-1 (Th1) and Th2 cytokines after allogeneic hematopoietic stem cell transplantation (allo-HSCT). AB - Dysregulation of T-helper (Th)1 (IFN-g, IL-2, TNF-a) and Th2 (IL-4, IL-5, IL-10) type cytokines has been suggested in the pathogenesis of graft versus host disease (GvHD). We analyzed intracellular cytokine expression in Th (CD4+) lymphocytes in 23 patients undergoing allo-hematopoietic stem cell transplantation (HSCT) both in the week of neutrophil engraftment (S1) and on the posttransplant 100th day (S2). CD4+TNF-a+ cells increased from 22% at S1 to 26% at S2 in the allo-peripheral blood (PB) group. CD4+IL-2+ cells at S1 in the bone marrow (BM) group had a tendency to be higher than in the allo-PB group and also higher than at S2. IL-2 and TNF-a expressions at S1 were significantly higher and IL-2 expression at S2 was significantly lower in patients with grade II-IV acute GvHD compared with grade 0-I GvHD. IFN-g expression tended to be higher at S2 in the chronic GvHD group compared with the patient without GvHD. Consequently, the data in this study support the role of Th1 cytokines in GvHD. PMID- 27264148 TI - Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia. AB - Gemtuzumab ozogamicin (GO, MylotargTM) is an antibody-targeted chemotherapy agent that has been studied in acute myeloid leukemia (AML) at first relapse in adults. There is limited experience in pediatric patients. We report six patients with refractory/relapsed CD33+AML who were treated with GO on compassionate-use basis. One patient attained remission. One patient is still alive following hematopoietic stem cell transplantation (HSCT), and one patient died in remission. Two patients were refractory and three patients had a response with <5% blasts in the bone marrow. Fever and chills, hypotension and hypoxia were observed as side effects. Three patients developed veno-occlusive disease (VOD) of the liver. Two of these three patients had persistence of VOD at the time of their deaths. One patient treated postSCT had bone marrow response without VOD. GO should be used cautiously in chemotherapy-refractory AML pediatric patients due to the high incidence of VOD. PMID- 27264149 TI - Hemophagocytic syndrome with erythrocyte phagocytosis by the myeloid precursors in a patient with AML -M2. AB - Hemophagocytic syndrome is characterized by fever, fatigue, weight loss, lymphadenopathy, and laboratory abnormalities including pancytopenia, liver dysfunction, hypertriglyceridemia and hyperfibrinemia. Histopathologically, lesions are characterized by mononuclear cell infiltration with marked histiocyte proliferation and phagocytosis of erythrocytes, leukocytes, platelets and their precursors by activated macrophages in the reticuloendothelial tissues. Hemophagocytic syndrome may develop from strong immunological stimuli such as severe infection, malignancy and autoimmune diseases. We present a 73-year-old man with acute myeloblastic leukemia FAB M2 type (AML M2) whose bone marrow histology showed unusual hemophagocytosis by myeloid cells and myeloblasts. PMID- 27264150 TI - Albendazole-induced bicytopenia. AB - Echinococcosis is a parasitic disease which occurs due to cyst hydatid Echinococcus granulosus and occurs in the liver in 55-70% of cases. Cyst hydatid treatment can be performed in three ways: primary surgery, medical and PAIR (Puncture Aspiration Injection Reaspiration) treatment. Medical treatment can be applied with PAIR in order to decrease post-surgery recurrence and facilitate the treatment in repeating cases. The most commonly used agent in medical treatment is albendazole. The most common albendazole-induced side effect is elevated levels of liver enzymes. It rarely causes bone marrow toxic consequences. We present herein a case with albendazole-induced leukopenia and thrombocytopenia, which to our knowledge has never been reported in the literature. PMID- 27264151 TI - First observation of homozygote Hb Q-Iran (alpha 75 (EF4) Asp-His). AB - The first observation of homozygote Hb Q-Iran (alpha1 75(EF4) Asp-His) is presented in this report. The clinical and hematological data of the index case, his father and mother showed that homozygous or heterozygous Hb Q-Iran has no clinical importance. PMID- 27264152 TI - First observation of Hb D-Ouled Rabah [beta19(B1)Asn>Lys] in the Turkish population. AB - Hb D-Ouled Rabah [beta19(B1)Asn>Lys] is a rare hemoglobin (Hb) beta chain variant reported from Tuareg tribes in Algeria and once from China. It was suggested that Hb D-Ouled Rabah might be specific of Berber-speaking populations. Our report describes the first observation of this hemoglobin variant in the Turkish population. PMID- 27264153 TI - Pearson syndrome associated with hemophagocytic syndrome in a child. PMID- 27264154 TI - Is it a sea-blue histiocyte? PMID- 27264155 TI - Extended dissipative state estimation for memristive neural networks with time varying delay. AB - This paper investigates the problem of extended dissipative state estimation for memristor-based neural networks (MNNs) with time-varying delay. Based on both nonsmooth analysis and the construction of a new Lyapunov-Krasovskii functional, the extended dissipative state estimation criteria are obtained by mainly applying differential inclusions, set-valued maps and many new integral inequalities. The extended dissipative state estimation can be adopted to deal with l2-linfinity state estimation, Hinfinity state estimation, passive state estimation and dissipative state estimation by valuing the corresponding weighting matrices. Finally, two numerical examples are given to show the effectiveness and less conservatism of the proposed criteria. PMID- 27264156 TI - FDI based on Artificial Neural Network for Low-Voltage-Ride-Through in DFIG-based Wind Turbine. AB - As per modern electrical grid rules, Wind Turbine needs to operate continually even in presence severe grid faults as Low Voltage Ride Through (LVRT). Hence, a new LVRT Fault Detection and Identification (FDI) procedure has been developed to take the appropriate decision in order to develop the convenient control strategy. To obtain much better decision and enhanced FDI during grid fault, the proposed procedure is based on voltage indicators analysis using a new Artificial Neural Network architecture (ANN). In fact, two features are extracted (the amplitude and the angle phase). It is divided into two steps. The first is fault indicators generation and the second is indicators analysis for fault diagnosis. The first step is composed of six ANNs which are dedicated to describe the three phases of the grid (three amplitudes and three angle phases). Regarding to the second step, it is composed of a single ANN which analysis the indicators and generates a decision signal that describes the function mode (healthy or faulty). On other hand, the decision signal identifies the fault type. It allows distinguishing between the four faulty types. The diagnosis procedure is tested in simulation and experimental prototype. The obtained results confirm and approve its efficiency, rapidity, robustness and immunity to the noise and unknown inputs. PMID- 27264157 TI - Speed/position sensor fault tolerant control in adjustable speed drives - A review. AB - The position sensor is one of the most used devices in Adjustable Speed Drives (ASDs). Its use is mandatory in electric machines vector control. In this paper, an interest was addressed to this field. Indeed, a bibliographical review, about Fault Detection and Isolation (FDI) and Fault Tolerant Control (FTC) in ASDs, is presented. Thus, the paper deals with position sensor FDI and sensorless control based FTC in ASDs. Moreover, this issue is mainly addressed to position sensor faults in ASDs. This paper is based on a wide literature review referring to scientific papers and manufacturer's technical documents. In total, 186 references in the open literature, dating back to 1981, have been investigated in order to perform this study. PMID- 27264158 TI - Misdiagnosed neurosyphilis associated with prolonged psychosis. AB - OBJECTIVE: After the prevalence of syphilis had reached historic lows, the Center for Disease Control devised a plan to eradicate syphilis in the United States. Since that decree there has been a dramatic rise in new cases. Psychosis is an ominous symptom of neurosyphilis. METHODS: We report a case of neurosyphilis that was misdiagnosed and staged incorrectly. RESULTS: Failure to diagnose neurosyphilis was associated with prolonged psychosis that has been refractory to antipsychotic treatment. CONCLUSION: Psychiatrists should renew their vigilance for neurosyphilis in the setting of a positive screening test and psychosis. PMID- 27264159 TI - Effect of Roux-en-Y gastric bypass and sleeve gastrectomy on taste acuity and sweetness acceptability in postsurgical subjects. AB - OBJECTIVE: Data on taste acuity after bariatric surgery are scarce, and taste perception after sleeve gastrectomy, to our knowledge, has never been investigated. The objective of this work was to retrospectively compare taste acuity and sweetness acceptability after Roux-en-Y gastric bypass and sleeve gastrectomy. METHODS: Subjects with a postoperative period >=6 mo were recruited (between January and June 2012) for a non-randomized, observational study. Subjects completed sensory evaluation sessions consisting of measurement of detection thresholds for bitterness and sweetness (N = 21), saltiness and sourness (N = 19), and sweetness acceptability (N = 19). Significance was established with Tukey's honest significant difference test and analysis of variance using the SAS GLM procedure. RESULTS: Sourness threshold was significantly higher among subjects who had undergone Roux-en-Y gastric bypass (P = 0.0045). No other differences were obtained for the other thresholds or sweetness acceptability (P > 0.05). CONCLUSIONS: Further randomized studies are needed to clarify these differences. PMID- 27264160 TI - Hydrogen-bond promoted nucleophilic fluorination: concept, mechanism and applications in positron emission tomography. AB - Due to the tremendous interest in carbon-fluorine bond-forming reactions, research efforts in this area have been dedicated to the development of facile processes to synthesize small fluorine-containing organic molecules. Among others, PET (Positron Emission Tomography) is one of the most important applications of fluorine chemistry. Recognizing the specific requirements of PET processes, some groups have focused on fluorination reactions using alkali metal fluorides, particularly through SN2-type reactions. However, a common "misconception" about the role of protic solvents and hydrogen bonding interactions in this class of reactions has hampered the employment of these excellent promoters. Herein, we would like to review recent discoveries in this context, showing straightforward nucleophilic fluorination reactions using alkali metal fluorides promoted by protic solvents. Simultaneous dual activation of reacting partners by intermolecular hydrogen bonding and the enhancement of the "effective fluoride nucleophilicity", which is Nature's biocatalytic approach with the fluorinase enzyme, are the key to this unprecedentedly successful nucleophilic fluorination. PMID- 27264161 TI - Antiproliferative activity of ruthenium(ii) arene complexes with mono- and bidentate pyridine-based ligands. AB - A series of Ru(II) arene complexes of mono- and bidentate N-donor ligands with carboxyl or ester groups and chlorido ancillary ligands were synthesised and structurally characterised. The complexes have a distorted tetrahedral piano stool geometry. The binding interaction was studied with calf thymus DNA (CT-DNA) by absorption titration, viscosity measurement, thermal melting, circular dichroism, ethidium bromide displacement assay and DNA cleavage of plasmid DNA (pBR322), investigated by gel electrophoresis. The dichlorido complexes bind covalently to DNA in the dark, similar to cisplatin, while the monochlorido complexes bind covalently on irradiation, similar to cisplatin analogues. The compounds are selectively cytotoxic against several tumour cell lines and show specific nonlinear correlation between dose and activity. This phenomenon is closely related to their potential to act preferentially as inhibitors of cell division. PMID- 27264162 TI - Dumped: How a Quest for Administrative Efficiency Lost a Doctor His Doctor. PMID- 27264163 TI - The economic burden of spinal muscular atrophy. AB - AIM: To evaluate the economic burden of spinal muscular atrophy (SMA). MATERIALS AND METHODS: This study used Department of Defense Military Healthcare System (MHS) data from 2003-2012. Healthcare costs were determined for patients with at least one inpatient or three outpatient claims with a diagnosis of SMA before 18 years of age and who had >= 6 months of data after first SMA diagnosis or expired within 6 months of initial diagnosis. A comparator cohort was selected using a 3:1 match based on age and gender. RESULTS: A total of 239 individuals with SMA diagnosis met the inclusion criteria along with 717 matched comparator patients. More patients with SMA had hospitalizations (69.5%) compared to the comparator cohort (17.2%, p < 0.001). Median total expenditures across all years of data for patients with SMA were $83 652 (25-75th percentile = $29 620-228 754) vs the comparator group of $4329 (25-75(th) percentile = $1229-10 062 (p < 0.001)) over an average (SD) of 6.9 +/- 3.6 years. The annualized mean costs of total healthcare expenditures were significantly higher for the SMA cases than the comparison cohort, $47 862 +/- 88 607 compared to $1861 +/- 6374, respectively (p < 0.001). The sub-group of patients with early diagnosis (n = 45) had 4.3 +/- 2.9 years of observation with a median cost of $167 921 ($53 349-678 412). Mean age (SD) at first observed SMA diagnosis was 7.5 +/- 6.4 years. Mean (SD) duration of follow-up after initial SMA diagnosis was 4.8 +/- 3.3 years, with a median post diagnosis cost of $60 213 ($18 229-192 559). The major costs for all patients were outpatient visits [median = $53 152 ($23 902-136 150)], followed by inpatient costs [median = $11 258 ($0-51 987)] and total prescription costs [median = $3167 ($943-13 283)]. LIMITATIONS: The analysis is limited to the data available and may under-estimate the total cost of SMA. CONCLUSIONS: Individuals with SMA have a high degree of morbidity, particularly those diagnosed during infancy. SMA patients have significant medical expenditures and high utilization of healthcare services. PMID- 27264165 TI - Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys. AB - BACKGROUND: Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. METHODS: Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial "sample" trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine "choice" trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. RESULTS: Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32 3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. CONCLUSIONS: These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder. PMID- 27264166 TI - Impact of prescription drug monitoring programs and pill mill laws on high-risk opioid prescribers: A comparative interrupted time series analysis. AB - BACKGROUND: Prescription drug monitoring programs (PDMPs) and pill mill laws were implemented to reduce opioid-related injuries/deaths. We evaluated their effects on high-risk prescribers in Florida. METHODS: We used IMS Health's LRx Lifelink database between July 2010 and September 2012 to identify opioid-prescribing prescribers in Florida (intervention state, N: 38,465) and Georgia (control state, N: 18,566). The pre-intervention, intervention, and post-intervention periods were: July 2010-June 2011, July 2011-September 2011, and October 2011 September 2012. High-risk prescribers were those in the top 5th percentile of opioid volume during four consecutive calendar quarters. We applied comparative interrupted time series models to evaluate policy effects on clinical practices and monthly prescribing measures for low-risk/high-risk prescribers. RESULTS: We identified 1526 (4.0%) high-risk prescribers in Florida, accounting for 67% of total opioid volume and 40% of total opioid prescriptions. Relative to their lower-risk counterparts, they wrote sixteen times more monthly opioid prescriptions (79 vs. 5, p<0.01), and had more prescription-filling patients receiving opioids (47% vs. 19%, p<0.01). Following policy implementation, Florida's high-risk providers experienced large relative reductions in opioid patients and opioid prescriptions (-536 patients/month, 95% confidence intervals [CI] -829 to -243; -847 prescriptions/month, CI -1498 to -197), morphine equivalent dose (-0.88mg/month, CI -1.13 to -0.62), and total opioid volume ( 3.88kg/month, CI -5.14 to -2.62). Low-risk providers did not experience statistically significantly relative reductions, nor did policy implementation affect the status of being high- vs. low- risk prescribers. CONCLUSIONS: High risk prescribers are disproportionately responsive to state policies. However, opioids-prescribing remains highly concentrated among high-risk providers. PMID- 27264167 TI - Significance and outcome of nuclear anaplasia and mitotic index in prostatic adenocarcinomas. AB - OBJECTIVES: The Gleason grading system measures architectural differentiation and disregards nuclear atypia and the cell proliferation index. Several studies have reported that nuclear grade and mitotic index (MI) are prognostically useful. PATIENTS AND METHODS: This study included 232 radical prostatectomy specimens. Nuclear anaplasia (NA) was determined on the basis of nucleomegali (at least 20um); vesicular chromatin; eosinophilic macronucleoli, nuclear lobulation, and irregular thickened nuclear membranei. The proportion of area of NA was recorded in each tumor in 10% increments. The MI was defined as the number of mitotic figures in 10 consecutive high-power fields (HPF). RESULTS: In univariate analysis, significant differences included associations between biochemical prostate-specific antigen recurrence (BCR) and Gleason score, extraprostatic extension, positive surgical margin, the presence of high-pathologic stage, NA>=10% of tumor area, MI>=3/10 HPF, and preoperative prostate-specific antigen. In a stepwise Cox regression model, a positive surgical margin, the presence of a NA>=10% of tumor area, and a MI of>=3/10 HPF were independent predictors of BCR after radical prostatectomy. NA>=10% of tumor area appeared to have a stronger association with outcome than MI>=3/10 HPF, as still associated with BCR when Gleason score was in the model. CONCLUSIONS: The results of our study showed that, in addition to the conventional Gleason grading system, NA, and MI are useful prognostic parameters while evaluating long-term prognosis in prostatic adenocarcinoma. PMID- 27264168 TI - Robotic cystectomy and intracorporeal stoma formation: Robotic management of ureteric strictures. PMID- 27264169 TI - National comparison of oncologic quality indicators between open and robotic assisted radical cystectomy. AB - INTRODUCTION: Despite increased adoption of robotic-assisted radical cystectomy (RARC), no national data have validated its oncologic efficacy compared to the "standard" open radical cystectomy (ORC). Positive surgical margins (PSM) and lymph node (LN) yield during radical cystectomy (RC) have an established relationship with bladder cancer outcomes. Here, we propose these 2 as quality indicators for RC and assess their differences to compare the oncologic efficacy between RARC and ORC. METHODS: Using the National Cancer Data Base for the years 2010 to 2012, all patients who underwent ORC or RARC were analyzed. Baseline demographic and cancer stage information were compared as well as unadjusted rates of PSM and LN yield. Survival effect of each indicator was assessed. Using propensity score adjustment, rates of PSM and LN yield were compared between RARC and ORC. RESULTS: A total of 12,036 patients are included who underwent RC, 20% (2,397) of which were performed robotically. Percentage RARC of total RC increased from 16.2% to 23.3% over the 3 study years. Compared to ORC, patients who underwent RARC were no different in age but were more often men (78.4% vs. 73.6%, P<0.001), had less-advanced cancer stage, and were more likely to have received neoadjuvant chemotherapy (20.9% vs. 14.5%, P<0.001). Most RARC procedures were performed at academic medical centers (66.1%). Unadjusted rates of PSM were lower in the RARC group (10.8% vs. 13.2%, P = 0.002) whereas median LN yield was higher in RARC patients (16 [interquartile range 9, 25] vs. 11 [interquartile range 5, 19], P<0.001). After propensity score covariate adjustment, there was no significant difference in PSM rate between RARC and ORC (-1.12% difference, [95% CI:-2.8, 0.32%]. However, RARC was associated with a higher node yield (+3.32 LN, [95% CI: 2.61, 4.03]) than ORC (P<0.001). CONCLUSION: The RARC is becoming more prevalent. In a national cohort, RARC was performed more often on men, with lower stage cancer, who were more likely to receive neoadjuvant chemotherapy. Controlling for these factors, RARC had comparable PSM rates but slightly higher LN yield than ORC. PMID- 27264170 TI - Enhancing Prefrontal Neuron Activity Enables Associative Learning of Temporally Disparate Events. AB - The ability to link events that are separated in time is important for extracting meaning from experiences and guiding behavior in the future. This ability likely requires the brain to continue representing events even after they have passed, a process that may involve the prefrontal cortex and takes the form of sustained, event-specific neuron activity. Here, we show that experimentally increasing the activity of excitatory neurons in the medial prefrontal cortex (mPFC) enables rats to associate two stimuli separated by a 750-ms long temporal gap. Learning is accompanied by ramping increases in prefrontal theta and beta rhythms during the interval between stimuli. This ramping activity predicts memory-related behavioral responses on a trial-by-trial basis but is not correlated with the same muscular activity during non-memory conditions. Thus, the enhancement of prefrontal neuron excitability extends the time course of evoked prefrontal network activation and facilitates the formation of associations of temporally disparate, but correlated, events. PMID- 27264172 TI - LSD1 Interacts with Zfp516 to Promote UCP1 Transcription and Brown Fat Program. AB - Zfp516, a brown fat (BAT)-enriched and cold-inducible transcription factor, promotes transcription of UCP1 and other BAT-enriched genes for non-shivering thermogenesis. Here, we identify lysine-specific demethylase 1 (LSD1) as a direct binding partner of Zfp516. We show that, through interaction with Zfp516, LSD1 is recruited to UCP1 and other BAT-enriched genes, such as PGC1alpha, to function as a coactivator by demethylating H3K9. We also show that LSD1 is induced during brown adipogenesis and that LSD1 and its demethylase activity is required for the BAT program. Furthermore, we show that LSD1 ablation in mice using Myf5-Cre alters embryonic BAT development. Moreover, BAT-specific deletion of LSD1 via the use of UCP1-Cre impairs the BAT program and BAT development, making BAT resemble WAT, reducing thermogenic activity and promoting obesity. Finally, we demonstrate an in vivo requirement of the Zfp516-LSD1 interaction for LSD1 function in BAT gene activation. PMID- 27264171 TI - Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4. AB - The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I IFN induction. We demonstrate that complete IFN-beta induction by live GC depends on both cGAS and TLR4. Type I IFN is detrimental to the host, and dysregulation of iron homeostasis genes may explain lower bacteria survival in cGAS(-/-) and TLR4(-/-) cells. Collectively, these observations reveal cooperation between TLRs and cGAS in immunity to GC infection. PMID- 27264173 TI - The Action of Discoidin Domain Receptor 2 in Basal Tumor Cells and Stromal Cancer Associated Fibroblasts Is Critical for Breast Cancer Metastasis. AB - High levels of collagen deposition in human and mouse breast tumors are associated with poor outcome due to increased local invasion and distant metastases. Using a genetic approach, we show that, in mice, the action of the fibrillar collagen receptor discoidin domain receptor 2 (DDR2) in both tumor and tumor-stromal cells is critical for breast cancer metastasis yet does not affect primary tumor growth. In tumor cells, DDR2 in basal epithelial cells regulates the collective invasion of tumor organoids. In stromal cancer-associated fibroblasts (CAFs), DDR2 is critical for extracellular matrix production and the organization of collagen fibers. The action of DDR2 in CAFs also enhances tumor cell collective invasion through a pathway distinct from the tumor-cell-intrinsic function of DDR2. This work identifies DDR2 as a potential therapeutic target that controls breast cancer metastases through its action in both tumor cells and tumor-stromal cells at the primary tumor site. PMID- 27264174 TI - A Specific Population of Reticulospinal Neurons Controls the Termination of Locomotion. AB - Locomotion requires the proper sequencing of neural activity to start, maintain, and stop it. Recently, brainstem neurons were shown to specifically stop locomotion in mammals. However, the cellular properties of these neurons and their activity during locomotion are still unknown. Here, we took advantage of the lamprey model to characterize the activity of a cell population that we now show to be involved in stopping locomotion. We find that these neurons display a burst of spikes that coincides with the end of swimming activity. Their pharmacological activation ends ongoing swimming, whereas the inactivation of these neurons dramatically impairs the rapid termination of swimming. These neurons are henceforth referred to as stop cells, because they play a crucial role in the termination of locomotion. Our findings contribute to the fundamental understanding of motor control and provide important details about the cellular mechanisms involved in locomotor termination. PMID- 27264176 TI - Innate Immune B Cell Activation by Leishmania donovani Exacerbates Disease and Mediates Hypergammaglobulinemia. AB - Participation of B cells in the immune response by various antibody-independent mechanisms has recently been uncovered. B cells producing cytokines have been described for several infections and appear to regulate the adaptive immune response. B cell activation by Leishmania donovani results in disease exacerbation. How Leishmania activates B cells is still unknown. We show that L. donovani amastigotes activate B cells by triggering endosomal TLRs; this activation leads to the induction of various cytokines. Cytokine expression is completely abrogated in B cells from Ifnar(-/-) mice upon exposure to L. donovani, suggesting an involvement of IFN-I in a positive feedback loop. IFN-I also appears to enhance the expression of endosomal TLRs following exposure to L. donovani. Cell-specific ablation of endosomal TLR signaling in B cells revealed that innate B cell activation by L. donovani is responsible for disease exacerbation through IL-10 and IFN-I production and for the promotion of hypergammaglobulinemia. PMID- 27264175 TI - STING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia. AB - Type I interferon (IFN), essential for spontaneous T cell priming against solid tumors, is generated through recognition of tumor DNA by STING. Interestingly, we observe that type I IFN is not elicited in animals with disseminated acute myeloid leukemia (AML). Further, survival of leukemia-bearing animals is not diminished in the absence of type I IFN signaling, suggesting that STING may not be triggered by AML. However, the STING agonist, DMXAA, induces expression of IFN beta and other inflammatory cytokines, promotes dendritic cell (DC) maturation, and results in the striking expansion of leukemia-specific T cells. Systemic DMXAA administration significantly extends survival in two AML models. The therapeutic effect of DMXAA is only partially dependent on host type I IFN signaling, suggesting that other cytokines are important. A synthetic cyclic dinucleotide that also activates human STING provided a similar anti-leukemic effect. These data demonstrate that STING is a promising immunotherapeutic target in AML. PMID- 27264177 TI - Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types. AB - Chemogenetic technologies, including the mutated human Gq-coupled M3 muscarinic receptor (hM3Dq), have greatly facilitated our ability to directly link changes in cellular activity to altered physiology and behavior. Here, we extend the hM3Dq toolkit with recombinase-responsive mouse lines that permit hM3Dq expression in virtually any cell type. These alleles encode a fusion protein designed to increase effective expression levels by concentrating hM3Dq to the cell body and dendrites. To illustrate their broad utility, we targeted three different genetically defined cell populations: noradrenergic neurons of the compact, bilateral locus coeruleus and two dispersed populations, Camk2a+ neurons and GFAP+ glia. In all three populations, we observed reproducible expression and confirmed that activation of hM3Dq is sufficient to dose-dependently evoke phenotypic changes, without extreme phenotypes associated with hM3Dq overexpression. These alleles offer the ability to non-invasively control activity of diverse cell types to uncover their function and dysfunction at any developmental stage. PMID- 27264178 TI - CEACAM1-Mediated Inhibition of Virus Production. AB - Cells in our body can induce hundreds of antiviral genes following virus sensing, many of which remain largely uncharacterized. CEACAM1 has been previously shown to be induced by various innate systems; however, the reason for such tight integration to innate sensing systems was not apparent. Here, we show that CEACAM1 is induced following detection of HCMV and influenza viruses by their respective DNA and RNA innate sensors, IFI16 and RIG-I. This induction is mediated by IRF3, which bound to an ISRE element present in the human, but not mouse, CEACAM1 promoter. Furthermore, we demonstrate that, upon induction, CEACAM1 suppresses both HCMV and influenza viruses in an SHP2-dependent process and achieves this broad antiviral efficacy by suppressing mTOR-mediated protein biosynthesis. Finally, we show that CEACAM1 also inhibits viral spread in ex vivo human decidua organ culture. PMID- 27264179 TI - A Computational Drug Repositioning Approach for Targeting Oncogenic Transcription Factors. AB - Mutations in transcription factor (TF) genes are frequently observed in tumors, often leading to aberrant transcriptional activity. Unfortunately, TFs are often considered undruggable due to the absence of targetable enzymatic activity. To address this problem, we developed CRAFTT, a computational drug-repositioning approach for targeting TF activity. CRAFTT combines ChIP-seq with drug-induced expression profiling to identify small molecules that can specifically perturb TF activity. Application to ENCODE ChIP-seq datasets revealed known drug-TF interactions, and a global drug-protein network analysis supported these predictions. Application of CRAFTT to ERG, a pro-invasive, frequently overexpressed oncogenic TF, predicted that dexamethasone would inhibit ERG activity. Dexamethasone significantly decreased cell invasion and migration in an ERG-dependent manner. Furthermore, analysis of electronic medical record data indicates a protective role for dexamethasone against prostate cancer. Altogether, our method provides a broadly applicable strategy for identifying drugs that specifically modulate TF activity. PMID- 27264180 TI - Targeting One Carbon Metabolism with an Antimetabolite Disrupts Pyrimidine Homeostasis and Induces Nucleotide Overflow. AB - Antimetabolites that affect nucleotide metabolism are frontline chemotherapy agents in several cancers and often successfully target one carbon metabolism. However, the precise mechanisms and resulting determinants of their therapeutic value are unknown. We show that 5-fluorouracil (5-FU), a commonly used antimetabolite therapeutic with varying efficacy, induces specific alterations to nucleotide metabolism by disrupting pyrimidine homeostasis. An integrative metabolomics analysis of the cellular response to 5-FU reveals intracellular uracil accumulation, whereas deoxyuridine levels exhibited increased flux into the extracellular space, resulting in an induction of overflow metabolism. Subsequent analysis from mice bearing colorectal tumors treated with 5-FU show specific secretion of metabolites in tumor-bearing mice into serum that results from alterations in nucleotide flux and reduction in overflow metabolism. Together, these findings identify a determinant of an antimetabolite response that may be exploited to more precisely define the tumors that could respond to targeting cancer metabolism. PMID- 27264181 TI - Two Mutually Exclusive Local Chromatin States Drive Efficient V(D)J Recombination. AB - Variable (V), diversity (D), and joining (J) (V(D)J) recombination is the first determinant of antigen receptor diversity. Understanding how recombination is regulated requires a comprehensive, unbiased readout of V gene usage. We have developed VDJ sequencing (VDJ-seq), a DNA-based next-generation-sequencing technique that quantitatively profiles recombination products. We reveal a 200 fold range of recombination efficiency among recombining V genes in the primary mouse Igh repertoire. We used machine learning to integrate these data with local chromatin profiles to identify combinatorial patterns of epigenetic features that associate with active VH gene recombination. These features localize downstream of VH genes and are excised by recombination, revealing a class of cis-regulatory element that governs recombination, distinct from expression. We detect two mutually exclusive chromatin signatures at these elements, characterized by CTCF/RAD21 and PAX5/IRF4, which segregate with the evolutionary history of associated VH genes. Thus, local chromatin signatures downstream of VH genes provide an essential layer of regulation that determines recombination efficiency. PMID- 27264182 TI - Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion. AB - Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development. PMID- 27264185 TI - Translaminar Cortical Membrane Potential Synchrony in Behaving Mice. AB - The synchronized activity of six layers of cortical neurons is critical for sensory perception and the control of voluntary behavior, but little is known about the synaptic mechanisms of cortical synchrony across layers in behaving animals. We made single and dual whole-cell recordings from the primary somatosensory forepaw cortex in awake mice and show that L2/3 and L5 excitatory neurons have layer-specific intrinsic properties and membrane potential dynamics that shape laminar-specific firing rates and subthreshold synchrony. First, while sensory and movement-evoked synaptic input was tightly correlated across layers, spontaneous action potentials and slow spontaneous subthreshold fluctuations had laminar-specific timing; second, longer duration forepaw movement was associated with a decorrelation of subthreshold activity; third, spontaneous and sensory evoked forepaw movements were signaled more strongly by L5 than L2/3 neurons. Together, our data suggest that the degree of translaminar synchrony is dependent upon the origin (sensory, spontaneous, and movement) of the synaptic input. PMID- 27264184 TI - FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair. AB - BRCA1/2 proteins function in homologous recombination (HR)-mediated DNA repair and cooperate with Fanconi anemia (FA) proteins to maintain genomic integrity through replication fork stabilization. Loss of BRCA1/2 proteins results in DNA repair deficiency and replicative stress, leading to genomic instability and enhanced sensitivity to DNA-damaging agents. Recent studies have shown that BRCA1/2-deficient tumors upregulate Poltheta-mediated alternative end-joining (alt-EJ) repair as a survival mechanism. Whether other mechanisms maintain genomic integrity upon loss of BRCA1/2 proteins is currently unknown. Here we show that BRCA1/2-deficient tumors also upregulate FANCD2 activity. FANCD2 is required for fork protection and fork restart in BRCA1/2-deficient tumors. Moreover, FANCD2 promotes Poltheta recruitment at sites of damage and alt-EJ repair. Finally, loss of FANCD2 in BRCA1/2-deficient tumors enhances cell death. These results reveal a synthetic lethal relationship between FANCD2 and BRCA1/2, and they identify FANCD2 as a central player orchestrating DNA repair pathway choice at the replication fork. PMID- 27264186 TI - Molecular Features Underlying Neurodegeneration Identified through In Vitro Modeling of Genetically Diverse Parkinson's Disease Patients. AB - The fact that Parkinson's disease (PD) can arise from numerous genetic mutations suggests a unifying molecular pathology underlying the various genetic backgrounds. To address this hypothesis, we took an integrated approach utilizing in vitro disease modeling and comprehensive transcriptome profiling to advance our understanding of PD progression and the concordant downstream signaling pathways across divergent genetic predispositions. To model PD in vitro, we generated neurons harboring disease-causing mutations from patient-specific, induced pluripotent stem cells (iPSCs). We observed signs of degeneration in midbrain dopaminergic neurons, reflecting the cardinal feature of PD. Gene expression signatures of PD neurons provided molecular insights into disease phenotypes observed in vitro, including oxidative stress vulnerability and altered neuronal activity. Notably, PD neurons show that elevated RBFOX1, a gene previously linked to neurodevelopmental diseases, underlies a pattern of alternative RNA-processing associated with PD-specific phenotypes. PMID- 27264183 TI - Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte Derived Dendritic Cells. AB - Both classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs) are capable of cross priming CD8(+) T cells in response to cell-associated antigens. We found that Ly 6C(hi)TREML4(-) monocytes can differentiate into Zbtb46(+) Mo-DCs in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL 4) but that Ly-6C(hi)TREML4(+) monocytes were committed to differentiate into Ly 6C(lo)TREML4(+) monocytes. Differentiation of Zbtb46(+) Mo-DCs capable of efficient cross-priming required both GM-CSF and IL-4 and was accompanied by the induction of Batf3 and Irf4. However, monocytes require IRF4, but not BATF3, to differentiate into Zbtb46(+) Mo-DCs capable of cross-priming CD8(+) T cells. Instead, Irf4(-/-) monocytes differentiate into macrophages in response to GM-CSF and IL-4. Thus, cDCs and Mo-DCs require distinct transcriptional programs of differentiation in acquiring the capacity to prime CD8(+) T cells. These differences may be of consideration in the use of therapeutic DC vaccines based on Mo-DCs. PMID- 27264187 TI - CYLD Proteolysis Protects Macrophages from TNF-Mediated Auto-necroptosis Induced by LPS and Licensed by Type I IFN. AB - Tumor necrosis factor (TNF) induces necroptosis, a RIPK3/MLKL-dependent form of inflammatory cell death. In response to infection by Gram-negative bacteria, multiple receptors on macrophages, including TLR4, TNF, and type I IFN receptors, are concurrently activated, but it is unclear how they crosstalk to regulate necroptosis. We report that TLR4 activates CASPASE-8 to cleave and remove the deubiquitinase cylindromatosis (CYLD) in a TRIF- and RIPK1-dependent manner to disable necroptosis in macrophages. Inhibiting CASPASE-8 leads to CYLD-dependent necroptosis caused by the TNF produced in response to TLR4 ligation. While lipopolysaccharides (LPS)-induced necroptosis was abrogated in Tnf(-/-) macrophages, a soluble TNF antagonist was not able to do so in Tnf(+/+) macrophages, indicating that necroptosis occurs in a cell-autonomous manner. Surprisingly, TNF-mediated auto-necroptosis of macrophages requires type I IFN, which primes the expression of key necroptosis-signaling molecules, including TNFR2 and MLKL. Thus, the TNF necroptosis pathway is regulated by both negative and positive crosstalk. PMID- 27264190 TI - Efficient planar Sb2S3 solar cells using a low-temperature solution-processed tin oxide electron conductor. AB - Efficient planar antimony sulfide (Sb2S3) heterojunction solar cells have been made using chemical bath deposited (CBD) Sb2S3 as the absorber, low-temperature solution-processed tin oxide (SnO2) as the electron conductor and poly (3 hexylthiophene) (P3HT) as the hole conductor. A solar conversion efficiency of 2.8% was obtained at 1 sun illumination using a planar device consisting of F doped SnO2 substrate/SnO2/CBD-Sb2S3/P3HT/Au, whereas the solar cells based on a titanium dioxide (TiO2) electron conductor exhibited a power conversion efficiency of 1.9%. Compared with conventional Sb2S3 sensitized solar cells, the high-temperature processed mesoscopic TiO2 scaffold is no longer needed. More importantly, a low-temperature solution-processed SnO2 layer was introduced for electron transportation to substitute the high-temperature sintered dense blocking TiO2 layer. Our planar solar cells not only have simple geometry with fewer steps to fabricate but also show enhanced performance. The higher efficiency of planar Sb2S3 solar cell devices based on a SnO2 electron conductor is attributed to their high transparency, uniform surface, efficient electron transport properties of SnO2, suitable energy band alignment, and reduced recombination at the interface of SnO2/Sb2S3. PMID- 27264188 TI - Robustness of MEK-ERK Dynamics and Origins of Cell-to-Cell Variability in MAPK Signaling. AB - Cellular signaling processes can exhibit pronounced cell-to-cell variability in genetically identical cells. This affects how individual cells respond differentially to the same environmental stimulus. However, the origins of cell to-cell variability in cellular signaling systems remain poorly understood. Here, we measure the dynamics of phosphorylated MEK and ERK across cell populations and quantify the levels of population heterogeneity over time using high-throughput image cytometry. We use a statistical modeling framework to show that extrinsic noise, particularly that from upstream MEK, is the dominant factor causing cell to-cell variability in ERK phosphorylation, rather than stochasticity in the phosphorylation/dephosphorylation of ERK. We furthermore show that without extrinsic noise in the core module, variable (including noisy) signals would be faithfully reproduced downstream, but the within-module extrinsic variability distorts these signals and leads to a drastic reduction in the mutual information between incoming signal and ERK activity. PMID- 27264189 TI - The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches. AB - Long non-coding RNAs (lncRNAs) have an undefined role in the pathobiology of glioblastoma multiforme (GBM). These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs) that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2) as a subtype-specific hypoxia-inducible lncRNA, upregulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal, and hypoxia-dependent molecular reprogramming. Among the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Downregulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs' speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome and targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context. PMID- 27264192 TI - Complex, Complicated, Simple. PMID- 27264191 TI - Ethanol Extract of Cissus quadrangularis Enhances Osteoblast Differentiation and Mineralization of Murine Pre-Osteoblastic MC3T3-E1 Cells. AB - Traditional medicinal literature and previous studies have reported the possible role of Cissus quadrangularis (CQ) as an anti-osteoporotic agent. This study examines the effectiveness of CQ in promoting osteoblast differentiation of the murine pre-osteoblast cell line, MC3T3-E1. Ethanolic extract of CQ (CQ-E) was found to affect growth kinetics of MC3T3-E1 cells in a dosage-dependent manner. High concentrations of CQ-E (more than 10 MUg/ml) have particularly adverse effects, while lower concentrations of 0.1 and 1 ug/ml were non-toxic and did not affect cell viability. Notably, cell proliferation was significantly increased at the lower concentrations of CQ-E. CQ-E treatment also augmented osteoblast differentiation, as reflected by a substantial increase in expression of the early osteoblast marker ALP activity, and at later stage, by mineralization of extracellular matrix compared to the control group. These findings suggest dose dependent effect of CQ-E with lower concentrations exhibiting anabolic and osteogenic properties. J. Cell. Physiol. 232: 540-547, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27264193 TI - Pericardial effusion due to cholesterol pericarditis in case of rheumatoid arthritis. PMID- 27264194 TI - Sirtuin 1 evaluation with a novel immunoassay approach based on TiO2-Au label and hyperbranched polymer hybrid. AB - Accurate and highly sensitive evaluation of the sirtuin 1 (SirT1) level is becoming increasingly important for understanding the contribution of SirT1 in metabolism pathways. Here, a novel electrochemical immunoassay of SirT1 based on crosslinked hyperbranched azo-polymer decorated with gold colloids (Au-HAP) as sensing platform and titanium dioxide (TiO2)-Au nanocomposites to immobilize secondary antibody-horseradish peroxidase (Ab2-HRP) as electrochemical labels has been designed. Greatly enhanced sensitivity was achieved by exploiting the excellent conductivity of Au nanoparticle, the amplification effect of Au-HAP and TiO2-Au, and the favorable catalytic ability of HRP. The nanocomposites of Au-HAP and TiO2-Au could attach numerous capture antibodies on the surface for significant immune recognition efficiency. Meanwhile, the TiO2-Au-labeled Ab2-HRP using an HRP-thionine-H2O2 (hydrogen peroxide) detection system could further induce signal readout. Under optimal conditions, the signal intensity was linearly related to the concentration of SirT1 in the range of 1-500 ng ml(-1), and the limit of detection was 0.28 ng ml(-1). The developed biosensor exhibits attractive performance for the analysis of SirT1, with rapid response, high sensitivity, and high accuracy, and could become a promising technique for protein detection. PMID- 27264195 TI - Parallel selective pressures drive convergent diversification of phenotypes in pythons and boas. AB - Pythons and boas are globally distributed and distantly related radiations with remarkable phenotypic and ecological diversity. We tested whether pythons, boas and their relatives have evolved convergent phenotypes when they display similar ecology. We collected geometric morphometric data on head shape for 1073 specimens representing over 80% of species. We show that these two groups display strong and widespread convergence when they occupy equivalent ecological niches and that the history of phenotypic evolution strongly matches the history of ecological diversification, suggesting that both processes are strongly coupled. These results are consistent with replicated adaptive radiation in both groups. We argue that strong selective pressures related to habitat-use have driven this convergence. Pythons and boas provide a new model system for the study of macro evolutionary patterns of morphological and ecological evolution and they do so at a deeper level of divergence and global scale than any well-established adaptive radiation model systems. PMID- 27264196 TI - (90) Y/(177) Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation. AB - Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid (CHX-A"-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 +/- 0.27 GBq/mg for (90) Y-CHX-A"-DTPA-Cetuximab and 1.14 +/- 0.15 GBq/mg for (177) Lu-CHX-A"-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-A"-DTPA-Cetuximab and (177) Lu-CHX A"-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-A"-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation. PMID- 27264197 TI - SMARCE1, a rare cause of Coffin-Siris Syndrome: Clinical description of three additional cases. AB - Coffin-Siris syndrome (CSS, MIM 135900), is a well-described, multiple congenital anomaly syndrome characterized by coarse facial features, hypertrichosis, sparse scalp hair, and hypo/aplastic digital nails and phalanges, typically of the 5th digits. Mutations in the BAF (SWI/SNF)-complex subunits (SMARCA4, SMARCE1, SMARCB1, SMARCA2, ARID1B, and ARID1A) have been shown to cause not only CSS, but also related disorders including Nicolaides-Baraitser (MIM 601358) syndrome and ARID1B-intellectual disability syndrome (MIM 614562). At least 200 individuals with CSS have been found to have a mutation in the BAF pathway. However, to date, only three individuals with CSS have been reported to have pathogenic variants in SMARCE1. We report here three additional individuals with clinical features consistent with CSS and alterations in SMARCE1, one of which is novel. The probands all exhibited dysmorphic facial features, moderate developmental and cognitive delay, poor growth, and hypoplastic digital nails/phalanges, including digits not typically affected in the other genes associated with CSS. Two of the three probands had a variety of different organ system anomalies, including cardiac disease, genitourinary abnormalities, feeding difficulties, and vision abnormalities. The 3rd proband has not had further investigative studies. Although an increasing number of individuals are being diagnosed with disorders in the BAF pathway, SMARCE1 is the least common of these genes. This report doubles the number of probands with these mutations, and allows for better phenotypic information of this rare syndrome. (c) 2016 Wiley Periodicals, Inc. PMID- 27264198 TI - Antipyretic Effect of Clonidine in Intensive Care Unit Patients: A Nested Observational Study. AB - Fever in the intensive care unit (ICU) is usually an adaptive response to infection or inflammation. Pharmacological intervention is often required in addition to addressing the underlying causes of fever. Animal studies have examined the antipyretic effect of clonidine; however, to our knowledge there are no clinical data available in humans. The observation of an antipyretic effect of clonidine was made during a single-center randomized control trial that was designed to study the effect of clonidine addition to the commonly used sedative agents in mechanically ventilated ICU patients. Forty patients 18 years or older on mechanical ventilation for 3 days or longer were randomized into 2 groups receiving clonidine and placebo. In addition to the usual sedation/analgesia, patients in the clonidine arm received enteral clonidine in doses of 0.1 mg 3 times a day (TID), which was increased to 0.2 mg TID if the hemodynamics remained stable. Vital signs, laboratory data, all cultures, and daily ICU events were recorded. The odds ratio of temperature higher than 38.3 degrees C was 3.96 times higher in the placebo group, after adjustment for the illness severity and the time of follow-up (P = .049). A lower temperature (0.52 degrees C) was observed in the clonidine group after adjustment for the time of follow-up (P = .006). Our report is the first of its kind in humans that demonstrates possible antipyretic properties of enteral clonidine in the critically ill intensive care unit patient. PMID- 27264199 TI - Deciphering the adaptation strategies of Desulfovibrio piezophilus to hydrostatic pressure through metabolic and transcriptional analyses. AB - Desulfovibrio piezophilus strain C1TLV30(T) is a mesophilic piezophilic sulfate reducer isolated from Wood Falls at 1700 m depth in the Mediterranean Sea. In this study, we analysed the effect of the hydrostatic pressure on this deep-sea living bacterium at the physiologic and transcriptomic levels. Our results showed that lactate oxidation and energy metabolism were affected by the hydrostatic pressure. Especially, acetyl-CoA oxidation pathway and energy conservation through hydrogen and formate recycling would be more important when the hydrostatic pressure is above (26 MPa) than below (0.1 MPa) the optimal one (10 MPa). This work underlines also the role of the amino acid glutamate as a piezolyte for the Desulfovibrio genus. The transcriptomic analysis revealed 146 differentially expressed genes emphasizing energy production and conversion, amino acid transport and metabolism and cell motility and signal transduction mechanisms as hydrostatic pressure responding processes. This dataset allowed us to identify a sequence motif upstream of a subset of differentially expressed genes as putative pressure-dependent regulatory element. PMID- 27264200 TI - Ex vivo detection of tumoral lymph nodes of colorectal origin with fluorescence imaging after intraoperative intravenous injection of indocyanine green. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the potential role of indocyanine green (ICG) fluorescence imaging after intraoperative intravenous (IV) injection for the "ex vivo" detection of metastatic lymph nodes (mLNs) of colorectal cancer origin. METHODS: Fresh-fixed LNs in cassettes and/or paraffin-embedded LNs of patients included in a study that evaluated the role of ICG in the detection of peritoneal metastases of colorectal origin (Protocol NCT 01995591) were further explored with a dedicated near-infrared camera system for their fluorescence. An IV injection of ICG was delivered intraoperatively at 0.25 mg/kg. Signal to background ratios (SBRs) were calculated. RESULTS: LNs on operative specimens were evaluated for 12 patients (5 males, 7 females). A total of 182 LNs were analyzed. The mean LN number per patient was 15.2 (median: 15.5; range 3-22). SBRs of mLNs were significantly more fluorescent than benign LNs, 1.41 versus 1.04 arbitrary units (P < 0.0002). On univariate analysis, fluorescence was statistically correlated with LN surface area (>20 mm(2) ) (P < 0.0004). CONCLUSION: Ex vivo ICG fluorescence imaging after intraoperative IV injection represents a potential method for detecting invaded LN's of colorectal cancer origin on operative specimens. Further clinical studies are needed to better define optimal techniques. J. Surg. Oncol. 2016;114:348-353. (c) 2016 Wiley Periodicals, Inc. PMID- 27264201 TI - Biomechanical properties of infantile hemangiomas: clinical stage and effect of age. AB - BACKGROUND: Infantile hemangiomas (IHs) are benign vascular neoplasms with rapid capillary proliferation shortly after birth and slow involution with diminishing capillary proliferative activity, fibrosis, and fatty replacement over 7-10 years. METHODS: Hemangiomas and contralateral control sites in 88 subjects were measured using a suction device, 6-mm probe and 200 mbar negative pressure. Mechanical properties were assessed vs. controls and effects of body site, depth, clinical stage, histology diagnosis, and time. RESULTS: Biological elasticity, overall elasticity, net elasticity, total recovery, and elastic recovery were lower for IH vs. controls (P < 0.001). IH total deformation, elastic deformation, viscoelastic creep, and residual deformation were higher than controls (P < 0.001). Involuting IHs had lower viscoelasticity than proliferating and stable lesions (P < 0.001) and lower viscoelastic creep than stable IHs (P = 0.04). IH viscoelasticity was higher at 2.3 than 12.9, 23.7, and 61.0 months and at 4.9 and 8.1 than 61.0 months. IH elastic recovery varied by body site with larger differences vs. control for abdomen and leg. Elastic recovery differences from control were smaller at younger vs. older ages. CONCLUSIONS: Measurement of biomechanical properties may be useful to characterize IH progression and treatment response in clinical settings. PMID- 27264202 TI - Delivery of membrane proteins into small and giant unilamellar vesicles by charge mediated fusion. AB - One of the current challenges in synthetic biology is the production of stable membrane mimetic systems and the insertion of components in these systems. Here, we employ fusion of oppositely charged liposomes to deliver separately reconstituted membrane proteins into a common lipid bilayer. After a systematic evaluation of different lipid compositions by lipid mixing and size distribution analysis, suitable conditions were further investigated for proteoliposome fusion. With this technique, we functionally coreconstituted bo3 oxidase and ATP synthase from Escherichia coli into unilamellar liposomes ranging from 100 nm to 50 MUm in size. The presented method is a simple and versatile tool for oriented membrane protein reconstitution to produce biomimetic systems with increased complexity. PMID- 27264203 TI - A scoping review of the nurse practitioner workforce in oncology. AB - The quality of cancer care may be compromised in the near future because of work force issues. Several factors will impact the oncology health provider work force: an aging population, an increase in the number of cancer survivors, and expansion of health care coverage for the previously uninsured. Between October 2014 and March 2015, an electronic literature search of English language articles was conducted using PubMed((r)) , the Cumulative Index to Nursing and Allied Health Sciences (CINAHL((r)) ), Web of Science, Journal Storage (JSTOR((r)) ), Google Scholar, and SCOPUS((r)) . Using the scoping review criteria, the research question was identified "How much care in oncology is provided by nurse practitioners (NPs)?" Key search terms were kept broad and included: "NP" AND "oncology" AND "workforce". The literature was searched between 2005 and 2015, using the inclusion and exclusion criteria, 29 studies were identified, further review resulted in 10 relevant studies that met all criteria. Results demonstrated that NPs are utilized in both inpatient and outpatient settings, across all malignancy types and in a variety of roles. Academic institutions were strongly represented in all relevant studies, a finding that may reflect the Accreditation Council for Graduate Medical Education (ACGME) duty work hour limitations. There was no pattern associated with state scope of practice and NP representation in this scoping review. Many of the studies reviewed relied on subjective information, or represented a very small number of NPs. There is an obvious need for an objective analysis of the amount of care provided by oncology NPs. PMID- 27264204 TI - Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: differences and similarities. AB - Haemophagocytic lymphohistiocytosis (HLH) comprises a heterogeneous spectrum of hyperinflammatory conditions that are inherited (primary HLH) or acquired in a context of infections, malignancies or autoimmune/autoinflammatory disorders (secondary HLH). Genetic defects in the cytotoxic machinery of natural killer and CD8(+) T cells underlie primary HLH, with residual cytotoxicity determining disease severity. Improved sequencing techniques have expanded the range of causal mutations and have redefined many cases of secondary HLH as primary HLH and vice versa, blurring the distinction between both subtypes. These insights allow HLH to be conceptualized as a threshold disease, in which interplay between various genetic and environmental factors causes progressive inflammation into a critical point, beyond which uncontrolled activation of immune cells and excessive cytokine production give rise to the cardinal symptoms of HLH. Various pathogenic pathways may thus converge to a common end stage of fulminant HLH. PMID- 27264205 TI - GABA quantitation using MEGA-PRESS: Regional and hemispheric differences. AB - PURPOSE: To measure in vivo brain gamma-aminobutyric acid (GABA) concentrations, and assess regional and hemispheric differences, using MR spectroscopy (1 H-MRS). MATERIALS AND METHODS: GABA concentrations were measured bilaterally in the frontal cortex (FC), parietal cortex (PC), and occipital cortex (OC) of 21 healthy young subjects (age range 20-29 years) using 3 Tesla Philips scanner. A univariate general linear model analysis was carried out to assess the effect of region and hemisphere as well as their interaction on GABA concentrations while controlling for sex and gray matter differences. RESULTS: Results indicated a significant regional dependence of GABA levels [F(2,89) = 11.725, P < 0.001, etap2 = .209] with lower concentrations in the FC compared with both PC (P < 0.001) and OC (P < 0.001) regions. There was no significant hemispheric differences in GABA levels [F(1,89) = .172; P = 0.679; etap2 = .002]. CONCLUSION: This study reports the concentrations of GABA in the FC, PC, and OC brain regions of healthy young adults. GABA distribution exhibits hemispheric symmetry, but varies across regions; GABA levels in the FC are lower than those in the PC and OC. J. Magn. Reson. Imaging 2016;44:1619-1623. PMID- 27264207 TI - Using novel biomarkers to triage young adult women with minor cervical lesions: a cost-effectiveness analysis. AB - OBJECTIVE: To evaluate the short-term consequences and cost-effectiveness associated with the use of novel biomarkers to triage young adult women with minor cervical cytological lesions. DESIGN: Model-based economic evaluation using primary epidemiological data from Norway, supplemented with data from European and American clinical trials. SETTING: Organised cervical cancer screening in Norway. POPULATION: Women aged 25-33 years with minor cervical cytological lesions detected at their primary screening test. METHODS: We expanded an existing simulation model to compare 12 triage strategies involving alternative biomarkers (i.e. reflex human papillomavirus (HPV) DNA/mRNA testing, genotyping, and dual staining) with the current Norwegian triage guidelines. MAIN OUTCOME MEASURES: The number of high-grade precancers detected and resource use (e.g. monetary costs and colposcopy referrals) for a single screening round (3 years) for each triage strategy. Cost-efficiency, defined as the additional cost per additional precancer detected of each strategy compared with the next most costly strategy. RESULTS: Five strategies were identified as cost-efficient, and are projected to increase the precancer detection rate between 18 and 57%, compared with current guidelines; however, the strategies did not uniformly require additional resources. Strategies involving HPV mRNA testing required fewer resources, whereas HPV DNA-based strategies detected >50% more precancers, but were more costly and required twice as many colposcopy referrals compared with the current guidelines. CONCLUSION: Strategies involving biomarkers to triage younger women with minor cervical cytological lesions have the potential to detect additional precancers, yet the optimal strategy depends on the resources available as well as decision-makers' and women's acceptance of additional screening procedures. TWEETABLE ABSTRACT: Women with minor cervical lesions may be triaged more accurately and effectively using novel biomarkers. PMID- 27264206 TI - Correcting for binomial measurement error in predictors in regression with application to analysis of DNA methylation rates by bisulfite sequencing. AB - Motivated by a genetic application, this paper addresses the problem of fitting regression models when the predictor is a proportion measured with error. While the problem of dealing with additive measurement error in fitting regression models has been extensively studied, the problem where the additive error is of a binomial nature has not been addressed. The measurement errors here are heteroscedastic for two reasons; dependence on the underlying true value and changing sampling effort over observations. While some of the previously developed methods for treating additive measurement error with heteroscedasticity can be used in this setting, other methods need modification. A new version of simulation extrapolation is developed, and we also explore a variation on the standard regression calibration method that uses a beta-binomial model based on the fact that the true value is a proportion. Although most of the methods introduced here can be used for fitting non-linear models, this paper will focus primarily on their use in fitting a linear model. While previous work has focused mainly on estimation of the coefficients, we will, with motivation from our example, also examine estimation of the variance around the regression line. In addressing these problems, we also discuss the appropriate manner in which to bootstrap for both inferences and bias assessment. The various methods are compared via simulation, and the results are illustrated using our motivating data, for which the goal is to relate the methylation rate of a blood sample to the age of the individual providing the sample. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27264208 TI - Ritonavir-Induced Suicidal Death of Human Erythrocytes. AB - The antiviral drug ritonavir has been shown to trigger suicidal death or apoptosis of tumour cells and has thus been considered for the treatment of malignancy. In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca(2+) entry with increase in cytosolic Ca(2+) activity ([Ca(2+) ]i ), oxidative stress and ceramide. The present study explored whether and how ritonavir induces eryptosis. To this end, flow cytometry was employed to estimate cell volume from forward scatter, phosphatidylserine exposure at the cell surface from Annexin-V binding, [Ca(2+) ]i from Fluo3 fluorescence, abundance of reactive oxygen species (ROS) from 2',7' dichlorodihydrofluorescein diacetate (DCFDA) fluorescence and ceramide abundance utilizing specific antibodies. As a result, a 48-hr exposure of human erythrocytes to ritonavir significantly increased the percentage of Annexin-V binding cells (>=5 MUg/ml), significantly decreased forward scatter (>=5 MUg/ml), significantly increased Fluo3 fluorescence (20 MUg/ml), slightly, but significantly increased DCFDA fluorescence (20 MUg/ml) and slightly, but significantly increased ceramide abundance (20 MUg/ml). The effect of ritonavir on Annexin-V binding was significantly blunted, but not fully abolished by the removal of extracellular Ca(2+) . In conclusion, ritonavir triggers erythrocyte shrinkage and phosphatidylserine translocation at the erythrocyte cell membrane, an effect in part due to the stimulation of Ca(2+) entry, oxidative stress and ceramide. PMID- 27264209 TI - 'Wouldn't it be easier if you continued to be a guy?' - a qualitative interview study of transsexual persons' experiences of encounters with healthcare professionals. AB - AIMS AND OBJECTIVES: To describe transsexual persons' experiences of encounters with healthcare professionals during the sex reassignment process. BACKGROUND: Transsexual persons are individuals who use varying means to alter their natal sex via hormones and/or surgery. Transsexual persons may experience stigma, which increases the risk of psychological distress. Mistreatments by healthcare professionals are common. Qualitative studies addressing transsexual persons' experiences of healthcare are scarce. DESIGN: Qualitative descriptive design. METHODS: A Swedish non-clinical convenience sample was used, consisting of six persons who had been diagnosed as transsexual, gone through sex reassignment surgery or were at the time of the interview awaiting surgery. Semi-structured interviews were undertaken, and data were analysed using manifest qualitative content analysis. RESULTS: Three categories and 15 subcategories were identified. The encounters were perceived as good when healthcare professionals showed respect and preserved the transsexual person's integrity, acted in a professional manner and were responsive and built trust and confidence. However, the participants experienced that healthcare professionals varied in their level of knowledge, exploited their position of power, withheld information, expressed gender stereotypical attitudes and often used the wrong name. They felt vulnerable by having a condescending view of themselves, and they could not choose not to be transsexual. They felt dependent on healthcare professionals, and that the external demands were high. CONCLUSIONS: Transsexual persons are in a vulnerable position during the sex reassignment surgery process. The encounters in healthcare could be negatively affected if healthcare professionals show inadequate knowledge, exploit their position of power or express gender stereotypical attitudes. A good encounter is characterised by preserved integrity, respect, responsiveness and trust. RELEVANCE TO CLINICAL PRACTICE: Improved education on transgender issues in nursing and medical education is warranted. Healthcare professionals should be aware of how their attitudes and their level of knowledge affect the care given during the sex reassignment surgery process. PMID- 27264210 TI - Gold nanoparticle capture within protein crystal scaffolds. AB - DNA assemblies have been used to organize inorganic nanoparticles into 3D arrays, with emergent properties arising as a result of nanoparticle spacing and geometry. We report here the use of engineered protein crystals as an alternative approach to biologically mediated assembly of inorganic nanoparticles. The protein crystal's 13 nm diameter pores result in an 80% solvent content and display hexahistidine sequences on their interior. The hexahistidine sequence captures Au25(glutathione)~17 (nitrilotriacetic acid)~1 nanoclusters throughout a chemically crosslinked crystal via the coordination of Ni(ii) to both the cluster and the protein. Nanoparticle loading was validated by confocal microscopy and elemental analysis. The nanoparticles may be released from the crystal by exposure to EDTA, which chelates the Ni(ii) and breaks the specific protein/nanoparticle interaction. The integrity of the protein crystals after crosslinking and nanoparticle capture was confirmed by single crystal X-ray crystallography. PMID- 27264211 TI - Exercise increases pressure pain tolerance but not pressure and heat pain thresholds in healthy young men. AB - BACKGROUND: Exercise causes an acute decrease in the pain sensitivity known as exercise-induced hypoalgesia (EIH), but the specificity to certain pain modalities remains unknown. This study aimed to compare the effect of isometric exercise on the heat and pressure pain sensitivity. METHODS: On three different days, 20 healthy young men performed two submaximal isometric knee extensions (30% maximal voluntary contraction in 3 min) and a control condition (quiet rest). Before and immediately after exercise and rest, the sensitivity to heat pain and pressure pain was assessed in randomized and counterbalanced order. Cuff pressure pain threshold (cPPT) and pain tolerance (cPTT) were assessed on the ipsilateral lower leg by computer-controlled cuff algometry. Heat pain threshold (HPT) was recorded on the ipsilateral foot by a computer-controlled thermal stimulator. RESULTS: Cuff pressure pain tolerance was significantly increased after exercise compared with baseline and rest (p < 0.05). Compared with rest, cPPT and HPT were not significantly increased by exercise. No significant correlation between exercise-induced changes in HPT and cPPT was found. Test retest reliability before and after the rest condition was better for cPPT and CPTT (intraclass correlation > 0.77) compared with HPT (intraclass correlation = 0.54). CONCLUSIONS: The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. SIGNIFICANCE: The effect of isometric exercise on pain tolerance may be relevant for patients in chronic musculoskeletal pain as a pain-coping strategy. WHAT DOES THIS STUDY ADD?: The results indicate that hypoalgesia after submaximal isometric exercise is primarily affecting tolerance of pressure pain compared with the heat and pressure pain threshold. These data contribute to the understanding of how isometric exercise influences pain perception, which is necessary to optimize the clinical utility of exercise in management of chronic pain. PMID- 27264212 TI - Extended left upper quadrant resection during primary cytoreductive surgery for Stage IV ovarian cancer. AB - OBJECTIVE: The completeness of primary cytoreductive surgery for Stage IV epithelial ovarian cancer is associated with greater progression free survival and overall survival Winter et al. (2008) [1]. Cytoreduction to no gross residual disease in patients with bulky upper abdominal disease presents significant surgical challenges, highlighting the importance of specialized and comprehensive surgical training in the treatment of advanced ovarian cancers Zivanovic et al. (2008) [2]. Extensive upper abdominal surgical procedures have shown to improve the ability to achieve cytoreduction to no gross residual disease Chi et al. (2004) [3]. This film displays an extended left upper quadrant resection in one of our recent patients. METHODS: The patient was a 62-year-old female with a CA 125 of 2,577U/mL, abdominal ascites, and a preoperative CT showing carcinomatosis with a left upper quadrant infiltration. Primary cytoreductive surgery was undertaken with exploratory laparotomy, type 2 radical oophorectomy (en bloc modified radical abdominal hysterectomy, bilateral salpingo-oophorectomy, pan pelvic peritonectomy, distal colectomy, retosigmoid colectomy), with en bloc omentectomy, transverse colectomy, splenectomy, distal pancreatectomy, and diaphragm peritonectomy. RESULTS: Operative time was 337min with an estimated blood loss of 900mL. The patient was discharged home on post-operative day 10 after a standard prolongation in hospitalization required to meet milestones after extensive upper quadrant cytoreductive surgery. CONCLUSION: Bulky upper abdominal disease can present significant surgical challenges. This film illustrates obtaining cytoreduction to no gross residual disease is feasible. We show transection of the pancreas by reinforced linear staple closure due to its ease of use and surgeon preference, although controversy remains regarding the ideal technique. PMID- 27264213 TI - Venous thromboembolism following minimally invasive surgery among women with endometrial cancer. AB - OBJECTIVE: To determine the rate of venous thromboembolism (VTE) among women undergoing minimally invasive surgery (MIS) for endometrial cancer. METHODS: Women undergoing robotic or laparoscopic hysterectomy for endometrial carcinoma or complex hyperplasia with atypia were identified between January 2009 and 2014 in a community based health care system. Patient data including age, race, cancer stage, grade, procedure type, length of hospital stay, use of prophylaxis, and diagnosis of VTE were collected retrospectively. The primary outcome was the rate of VTE within 30days following surgery. Fischer's exact tests were performed to evaluate factors associated with VTE. RESULTS: During the study period, 1433 patients underwent MIS for endometrial cancer, with 20 excluded due to known thrombophilia, VTE history, or long-term anticoagulation. A total of 1413 patients were included (739 robotic and 674 laparoscopic cases). All women received mechanical prophylaxis per hospital policy and 61% had additional pharmacologic prophylaxis. The rate of VTE was 0.35% (5/1413), which did not differ among those who received pharmacologic compared to mechanical prophylaxis (0.23% [2/865] versus 0.55% [3/548] respectively, p=0.38). No factors were associated with increased risk of VTE due to the low event rate. CONCLUSION: VTE in patients undergoing MIS for endometrial cancer was very low irrespective of the mode of prophylaxis received in this large cohort. National guidelines for VTE prophylaxis need to differentiate the low risk associated with MIS surgery from the risk associated with laparotomy for endometrial cancer. We recommend mechanical prophylaxis is sufficient for these women undergoing MIS. PMID- 27264214 TI - Percutaneous coronary intervention for older adults who present with syncope and coronary artery disease? Insights from the National Cardiovascular Data Registry. AB - BACKGROUND: We explored the risks/benefits of revascularization versus medical management in syncope patients with obstructive coronary artery disease (CAD). METHODS: We retrospectively examined Medicare patients >=65 years undergoing percutaneous coronary intervention (PCI) for syncope at 539 CathPCI Registry hospitals with >=70% stenosis in at least 1 coronary artery, excluding those with ST-segment elevation myocardial infarction (MI), cardiogenic shock, left main disease, and coronary artery bypass grafting. In a propensity-matched population, we compared short-term (90-day) all-cause readmission risk and long-term (3-year) risks of readmission for syncope and MI, as well as mortality in those receiving PCI versus medical management. RESULTS: Among 14,674 syncope patients, 9,549 (65%) had at least 1-vessel obstructive CAD. After exclusions, 3,196 of 7,338 patients (44%) underwent PCI. In the propensity-matched cohort, there was no significant difference in 90-day all-cause readmission risk (28.2% vs 30.3%, adjusted hazard ratio [HR] 0.92, 95% CI 0.83-1.02) or long-term risks of readmission for syncope (7.0% vs 6.1%, adjusted HR 1.06, 95% CI 0.83-1.35). PCI treated patients had significantly higher risk of readmission for MI (5.6% vs 4.0%, adjusted HR 1.56, 95% CI 1.18-2.06) but lower risk of long-term mortality (27.0% vs 30.3%, adjusted HR 0.86, 95% CI 0.77-0.97) than medically managed patients. CONCLUSIONS: In patients presenting with syncope and obstructive CAD, PCI was not associated with significant improvements in the risk of readmission but was associated with lower long-term mortality compared with medical therapy, suggesting the need to more definitively assess the benefit of PCI among elderly syncope patients. PMID- 27264215 TI - Rationale and design of the First Brazilian Cardiovascular Registry of Atrial Fibrillation: The RECALL study. AB - BACKGROUND: Atrial fibrillation (AF) is an important and growing public health problem worldwide, but data about its actual prevalence, therapeutic management, and clinical outcomes in middle- to low-income countries are scarce. DESIGN: The First Brazilian Cardiovascular Registry of Atrial Fibrillation (the RECALL study) will assess demographic characteristics and evidence-based practice of a representative sample of patients with AF in Brazil. The prospective, multicenter registry has a planned sample size of around 5,000 patients at approximately 80 sites. Eligibility criteria include age >18 years and permanent, paroxysmal, or persistent AF documented by electrocardiogram, 24-hour Holter monitoring, or device interrogation. Patients will be followed up through 1 year after enrollment. Information on laboratory tests, echocardiographic data, medication use, and clinical outcomes will be obtained. Various aspects of the population will be described, including demographic characteristics; antithrombotic therapies; antiarrhythmic agents; level of control of international normalized ratio (by average time within the therapeutic range) among patients using vitamin K antagonists; rates of warfarin discontinuation; outcomes such as death, stroke, systemic embolism, and major bleeding within 1 year after enrollment in the study; and rates of electrical cardioversion, percutaneous ablation of AF, ablation of the atrioventricular junction, and pacemaker/cardioverter defibrillator implantation. SUMMARY: RECALL is the first prospective, multicenter registry of AF in Brazil. This study will provide important information about demographics, practice patterns, treatments, and associated outcomes in patients with AF. The results of this registry will also allow Brazilian data to be put in perspective with other AF registries across the world and provide opportunities to improve care of patients with AF in Brazil. PMID- 27264216 TI - Impact of an Atrial Fibrillation Decision Support Tool on thromboprophylaxis for atrial fibrillation. AB - BACKGROUND: Appropriate thromboprophylaxis for patients with atrial fibrillation (AF) remains a national challenge. METHODS: We hypothesized that provision of decision support in the form of an Atrial Fibrillation Decision Support Tool (AFDST) would improve thromboprophylaxis for AF patients. We conducted a cluster randomized trial involving 15 primary care practices and 1,493 adults with nonvalvular AF in an integrated health care system between April 2014 and February 2015. Physicians in the intervention group received patient-level treatment recommendations made by the AFDST. Our primary outcome was the proportion of patients with antithrombotic therapy that was discordant from AFDST recommendation. RESULTS: Treatment was discordant in 42% of 801 patients in the intervention group. Physicians reviewed reports for 240 patients. Among these patients, thromboprophylaxis was discordant in 63%, decreasing to 59% 1 year later (P = .02). In nonstratified analyses, changes in discordant care were not significantly different between the intervention group and control groups. In multivariate regression models, assignment to the intervention group resulted in a nonsignificant trend toward decreased discordance (P = .29), and being a patient of a resident physician (P = .02) and a higher HAS-BLED score predicted decreased discordance (P = .03), whereas female gender (P = .01) and a higher CHADSVASc score (P = .10) predicted increased discordance. CONCLUSIONS: Among patients whose physicians reviewed recommendations of the decision support tool discordant therapy decreased significantly over 1 year. However, in nonstratified analyses, the intervention did not result in significant improvements in discordant antithrombotic therapy. PMID- 27264217 TI - Small-vessel treatment with contemporary newer-generation drug-eluting coronary stents in all-comers: Insights from 2-year DUTCH PEERS (TWENTE II) randomized trial. AB - BACKGROUND: Treatment of lesions in small vessels was associated with worse clinical outcome, and various definitions of "small vessels" have been used. Data with novel drug-eluting stents are scarce. METHODS: To compare the outcome of patients with vs without small-vessel treatment, we assessed 2-year follow-up data of the DUTCH PEERS randomized trial (ClinicalTrials.gov: NCT01331707), in which 1,811 all-comers were treated with contemporary zotarolimus-eluting (Resolute Integrity) or everolimus-eluting (Promus Element) stents. Primary end point was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS: The rates of TLF (9.5% vs 5.4%; P log rank = .001) and 2 individual components thereof-target vessel myocardial infarction (3.1% vs 1.3%; P log rank = .006) and target lesion revascularization (4.8% vs 2.8%; P log rank = .02)-were higher among 798 (44.1%) patients treated in at least one small vessel (<2.50 mm by quantitative coronary angiography). Multivariate analysis with propensity score adjustment demonstrated that treatment of small-vessel lesions independently predicted TLF at 2-year follow-up (hazard ratio 1.60, 95% CI 1.09-2.34). Patients with the smallest target vessel being <2.25 mm had TLF rates similar to patients with smallest target vessels of 2.25 to <2.50 mm; however, patients treated in vessels no smaller than 2.50 to <3.00 mm and patients treated in vessels >=3.00 mm had lower TLF rates (9.3%, 9.8%, 5.0%, and 5.8%, respectively; P log rank = .009). CONCLUSION: Patients treated with novel drug-eluting stents in small vessel lesions had higher adverse event rates than did patients who had no small vessel treatment. Our data suggest that with current stents, a vessel diameter <2.50 mm is a suitable threshold to identify small target vessels. PMID- 27264218 TI - Extended duration dual antiplatelet therapy in patients with myocardial infarction: A study-level meta-analysis of controlled randomized trials. AB - BACKGROUND: Whether dual antiplatelet therapy (DAPT) is beneficial beyond 1 year after myocardial infarction (MI) is not demonstrated; in particular, available studies may be individually underpowered for end points at low incidence, that is, major and fatal bleeding or mortality. We thus assessed the effectiveness and safety of prolonged DAPT after MI over the long term. METHODS: We conducted a systematic search to identify randomized trials on the topic; 3 studies and 21,534 post-MI patients receiving placebo or aspirin plus P2Y12 inhibition for >=2 years were included. Incidence of the following outcome measures was evaluated: major adverse cardiac events (MACE), major bleeding, fatal bleeding, and cardiovascular and noncardiovascular death. RESULTS: Occurrence of MACE was lower in patients treated with prolonged DAPT: 6.3% vs 7.9% in those without prolonged DAPT (odds ratios 0.74, 95% CI 0.60-0.91, P = .005); in the former, there was also a significant 16% reduction in cardiovascular mortality. Increase in major bleeding with extended duration DAPT was not significant in the overall analysis (1.5% vs 1.0%; P = .10), but became significant in the analysis restricted to patients receiving ticagrelor or prasugrel as second antiplatelet agent (odds ratios 2.16, 95% CI 1.63-2.86); prolonged use of DAPT did not raise rates of fatal bleeding or noncardiovascular mortality. CONCLUSION: Prolonged DAPT after MI reduces MACE and cardiovascular mortality over the long term; this was paralleled by higher risk of nonfatal major bleeding mainly with the newer, more potent P2Y12 antagonists. Tailoring duration of DAPT after MI on the comparative evaluation of both ischemic and bleeding risk is mandatory in this setting. PMID- 27264219 TI - Switching of platelet P2Y12 receptor inhibitors in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Review of the literature and practical considerations. AB - The combination of aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACSs) and in those undergoing percutaneous coronary intervention (PCI). At the present time, 3 different oral P2Y12 receptor inhibitors are available on the market; 2 have obtained the indication for ACS (clopidogrel and ticagrelor) and 1 for ACS with planned PCI (prasugrel). An intravenous direct acting P2Y12 inhibitor, cangrelor, has also been recently approved by US and European regulatory agencies for patients undergoing PCI. Although the correct timing and modality of transition from intravenous cangrelor to oral P2Y12 inhibitors is still controversial and needs further evidence, switching between oral P2Y12 receptor inhibitors frequently occurs in clinical practice for several reasons. This practice raises the question of the relative safety of this strategy and of which switching approaches are preferable. In this article, we review the data on switching antiplatelet treatment strategies with P2Y12 receptor inhibitors and discuss practical considerations for switching therapies in patients with ACS undergoing PCI. PMID- 27264221 TI - Protocol for analyses of adverse event data from randomized controlled trials of statin therapy. AB - The Cholesterol Treatment Trialists' (CTT) Collaboration was originally established to conduct individual participant data meta-analyses of major vascular events, cause-specific mortality, and site-specific cancers in large, long-term, randomized trials of statin therapy (and other cholesterol-modifying treatments). The results of the trials of statin therapy and their associated meta-analyses have shown that statins significantly reduce the risk of major vascular events without any increase in the risk of nonvascular causes of death or of site-specific cancer, but do produce small increases in the incidence of myopathy, diabetes, and, probably, hemorrhagic stroke. The CTT Collaboration has not previously sought data on other outcomes, and so a comprehensive meta analysis of all adverse events recorded in each of the eligible trials has not been conducted. This protocol prospectively describes plans to extend the CTT meta-analysis data set so as to provide a more complete understanding of the nature and magnitude of any other effects of statin therapy. PMID- 27264222 TI - Racial and ethnic differences in atrial fibrillation risk factors and predictors in women: Findings from the Women's Health Initiative. AB - BACKGROUND: The incidence of atrial fibrillation (AF) is higher in non-Hispanic whites (NHWs) compared with other race-ethnic groups, despite more favorable cardiovascular risk profiles. To explore reasons for this paradox, we compared the hazards of AF from traditional and other risk factors between 4 race-ethnic groups in a large cohort of postmenopausal women. METHODS: We included 114,083 NHWs, 11,876 African Americans, 5,174 Hispanics, and 3,803 Asians from the Women's Health Initiative free of AF at baseline. Women, averaging 63 years old, were followed up for incident AF using hospitalization records and diagnostic codes from Medicare claims. RESULTS: Over a mean of 13.7 years, 19,712 incident cases of AF were recorded. Despite a higher burden of hypertension, diabetes, and obesity, annual AF incidence was lower among nonwhites (0.7%, 0.4%, and 0.4% for African American, Hispanic, and Asian participants, respectively, compared with 1.2% for NHWs). The hazards of AF from hypertension, diabetes, obesity, heart failure, and coronary artery disease were similar across race-ethnic groups. Major risk factors, including hypertension, obesity, diabetes, smoking, peripheral arterial disease, coronary artery disease, and heart failure, accounted for an attributable risk of 50.3% in NHWs, 83.1% in African Americans, 65.6% in Hispanics, and 37.4% in Asians. Established AF prediction models performed comparably across race-ethnic groups. CONCLUSIONS: In this large study of postmenopausal women, traditional cardiovascular risk factors conferred a similar degree of individual risk of AF among 4 race-ethnic groups. However, major AF risk factors conferred a higher-attributable risk in African Americans and Hispanics compared with NHWs and Asians. PMID- 27264220 TI - Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial. AB - BACKGROUND: Anxiety is highly prevalent among patients with coronary heart disease (CHD), and there is growing evidence that high levels of anxiety are associated with worse prognosis. However, few studies have evaluated the efficacy of treating anxiety in CHD patients for reducing symptoms and improving clinical outcomes. Exercise and selective serotonin reuptake inhibitors have been shown to be effective in treating patients with depression, but have not been studied in cardiac patients with high anxiety. METHODS: The UNWIND trial is a randomized clinical trial of patients with CHD who are at increased risk for adverse events because of comorbid anxiety. One hundred fifty participants with CHD and elevated anxiety symptoms and/or with a diagnosed anxiety disorder will be randomly assigned to 12 weeks of aerobic exercise (3*/wk, 35 min, 70%-85% VO2peak), escitalopram (5-20 mg qd), or placebo. Before and after 12 weeks of treatment, participants will undergo assessments of anxiety symptoms and CHD biomarkers of risk, including measures of inflammation, lipids, hemoglobin A1c, heart rate variability, and vascular endothelial function. Primary outcomes include post intervention effects on symptoms of anxiety and CHD biomarkers. Secondary outcomes include clinical outcomes (cardiovascular hospitalizations and all-cause death) and measures of quality of life. CONCLUSIONS: The UNWIND trial (ClinicalTrials.gov NCT02516332) will evaluate the efficacy of aerobic exercise and escitalopram for improving anxiety symptoms and reducing risk for adverse clinical events in anxious CHD patients. PMID- 27264223 TI - Low real-world early stent thrombosis rates in ST-elevation myocardial infarction patients and the use of bivalirudin, heparin alone or glycoprotein IIb/IIIa inhibitor treatment: A nationwide Swedish registry report. AB - BACKGROUND: In recent studies of primary percutaneous coronary intervention (PCI), bivalirudin compared with heparin has been associated with increased risk of stent thrombosis (ST). Our aim was to describe incidence and outcome of definite, early ST in a large contemporary primary PCI population divided in antithrombotic therapy subgroups. METHODS AND RESULTS: A prospective, observational cohort study of all 31,258 ST-elevation myocardial infarction patients who received a stent in Sweden from January 2007 to July 2014 in the SWEDEHEART registry was conducted. Patients were divided into 3 groups: bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treated. Primary outcome measure was incidence of definite early ST (within 30 days of PCI). Secondary outcomes included all-cause mortality. Incidence of early ST was low, regardless of bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treatment (0.84%, 0.94%, and 0.83%, respectively). All-cause mortality at 1 year was 20.7% for all ST patients (n = 265), compared with 9.1% in those without ST (n = 31,286; P < .001). Patients with ST days 2-30 had numerically higher all cause mortality at 1 year compared with patients with ST days 0-1 (23% vs 16%, P = .20). CONCLUSION: In this real-world observational study of 31,258 ST-elevation myocardial infarction patients, the incidence of early ST was low, regardless of antithrombotic treatment strategy. Early ST was associated with increased mortality. Numerically higher all-cause mortality at 1 year was noted with ST days 2-30 compared with ST days 0-1 post-PCI. PMID- 27264224 TI - Impact of PCSK9 inhibition on coronary atheroma progression: Rationale and design of Global Assessment of Plaque Regression with a PCSK9 Antibody as Measured by Intravascular Ultrasound (GLAGOV). AB - BACKGROUND: Statin-mediated low-density lipoprotein cholesterol (LDL-C) lowering fails to prevent more than half of cardiovascular events in clinical trials. Serial plaque imaging studies have highlighted the benefits of aggressive LDL-C lowering, with plaque regression evident in up to two-thirds of patients with achieved LDL-C levels <70 mg/dL. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors permit LDL-C-lowering by a further 54% to 75% in statin treated patients. The impact of achieving very low LDL-C levels with PCSK9 inhibitors on coronary atherosclerosis has not been investigated. AIMS: To test the hypothesis that incremental LDL-C lowering with the PCSK9 inhibitor, evolocumab, will result in a significantly greater change from baseline in coronary atheroma volume than placebo in subjects receiving maximally tolerated statin therapy. METHODS: A phase 3, multicenter, double-blind, randomized, placebo-controlled trial evaluating the impact of evolocumab on coronary atheroma volume as assessed by serial coronary intravascular ultrasound at baseline in patients undergoing a clinically indicated coronary angiogram with angiographic evidence of coronary atheroma, and after 78 weeks of treatment. Subjects (n = 968) were randomized 1:1 into 2 groups to receive monthly either evolocumab 420 mg or placebo subcutaneous injections. CONCLUSIONS: The GLAGOV trial will explore whether greater degrees of plaque regression are achievable with ultrahigh intensity LDL-C lowering after combination statin-PCSK9 inhibitor therapy. GLAGOV will provide important mechanistic, safety, and efficacy data prior to the eagerly anticipated clinical outcomes trials testing the PCSK9 inhibitor hypothesis (www.clinicaltrials.gov identifier NCT01813422). PMID- 27264225 TI - Shock complicating type A acute aortic dissection: Clinical correlates, management, and outcomes. AB - AIMS: Shock is among the most dreaded and common complications of type A acute aortic dissection (TAAAD). However, clinical correlates, management, and short- and long-term outcomes of TAAAD patients presenting with shock in real-world clinical practice are not known. METHODS AND RESULTS: We evaluated 2,704 patients with TAAAD enrolled in the International Registry of Acute Aortic Dissection between January 1, 1996, and August 18, 2012. On admission, 407 (15.1%) TAAAD patients presented with shock. Most in-hospital complications (coma, myocardial or mesenteric ischemia or infarction, and cardiac tamponade) were more frequent in shock patients. In-hospital mortality was significantly higher in TAAAD patients with than without shock (30.2% vs 23.9%, P=.007), regardless of surgical or medical treatment. Most shock patients underwent surgical repair, with medically managed patients demonstrating older age and more complications at presentation. Estimates using Kaplan-Meier survival analysis indicated that most (89%) TAAAD patients with shock discharged alive from the hospital survived 5years, a rate similar to that of TAAAD patients without shock (82%, P=.609). CONCLUSIONS: Shock occurred in 1 of 7 TAAAD patients and was associated with higher rates of in-hospital adverse events and mortality. However, TAAAD survivors with or without shock showed similar long-term mortality. Successful early and aggressive management of shock in TAAAD patients has the potential for improving long-term survival in this patient population. PMID- 27264226 TI - Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation. AB - BACKGROUND: Oxidative stress plays an important role in the development of atrial fibrillation (AF). Arginine derivatives including asymmetric dimethylarginine (ADMA) are central to nitric oxide metabolism and nitrosative stress. Whether blood concentrations of arginine derivatives are related to incidence of AF is uncertain. METHODS AND RESULTS: In 3,310 individuals (mean age 58 +/- 10 years, 54% women) from the community-based Framingham Study, we prospectively examined the relations of circulating levels of ADMA, l-arginine, symmetric dimethylarginine (SDMA), and the ratio of l-arginine/ADMA to incidence of AF using proportional hazards regression models. Over a median follow-up time of 10 years, 247 AF cases occurred. Using age- and sex-adjusted regression models, ADMA was associated with a hazard ratio of 1.15 per 1-SD increase in loge-biomarker concentration (95% CI 1.02-1.29, P = .02) for AF, which was no longer significant after further risk factor adjustment (hazard ratio 1.09, 95% CI 0.97-1.23, P = .15). Neither l-arginine nor SDMA was related to new-onset AF. A clinical model comprising clinical risk factors for AF (for age, sex, height, weight, systolic blood pressure, diastolic blood pressure, current smoking, diabetes, hypertension treatment, myocardial infarction, and heart failure; c statistic = 0.781; 95% CI 0.753-0.808) was not improved by the addition of ADMA (0.782; 95% CI 0.755 0.809). CONCLUSIONS: Asymmetric dimethylarginine and related arginine derivatives were not associated with incident AF in the community after accounting for other clinical risk factors and confounders. Its role in the pathogenesis of AF needs further refinement. PMID- 27264227 TI - A clustered randomized trial to IMProve treatment with AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AF): design and rationale. AB - Atrial fibrillation (AF) is common, increasing as the population ages, and a major cause of embolic stroke. While oral anticoagulation (OAC) is highly effective at preventing stroke in patients with AF, it continues to be underused in eligible patients worldwide. The objective of this prospective, cluster randomized controlled trial (IMPACT-AF; ClinicalTrials.gov #NCT02082548) is to determine whether a comprehensive customized intervention will increase the rate and persistence of use of OAC in patients with AF. IMPACT-AF will be conducted in approximately 50 centers in 5 low- to middle-income countries. Before randomization, sites within countries will be paired to match in size, practice type and baseline rate of OAC use. Site pairs will be randomized to intervention versus control. In total, 40 to 70 patients with AF and at least 2 CHA2DS2-VASc risk factors will be enrolled at each site using a consecutive enrollment strategy, with the goal of capturing actual practice patterns. We aim for patients with a new diagnosis of AF to comprise at least 30% of the study cohort. Assuming an average baseline OAC use of 60% and a post-intervention use of 70% with a post-control rate of 60%, there will be roughly 94-98% power with 25 clusters per group (intracluster correlation coefficient of 0.02). While this trial focuses on improving treatment use and reducing preventable strokes, we also aim to better understand the reasons for OAC underuse. This will improve the intervention with the goal of creating educational recommendations to improve care for patients with AF. PMID- 27264228 TI - The on- and off-target effects of morphine in acute coronary syndrome: A narrative review. AB - With potent analgesic properties, perceived hemodynamic benefits and limited alternatives, morphine is the analgesic mainstay for patients with nitrate resistant chest pain due to acute Myocardial Infarction (MI). However, observational data suggest that morphine administration during MI may have negative consequences. While vomiting, hypotension and respiratory depression are established side effects, recent reports have demonstrated attenuated and delayed oral anti-platelet agent absorption, as well as suboptimal reperfusion after MI, all of which may translate into adverse cardiovascular outcomes. These data have resulted in reduced support for morphine in recent European and U.S. clinical practice guidelines for MI; despite the absence of any prospective randomized outcomes trials addressing this question. As such, randomized trials are now necessary to confirm whether or not morphine, which is administered in up to 30% of MI cases, causes adverse clinical outcomes in these patients. However, given that placebo-controlled randomized trial designs evaluating morphine in MI are limited by an ethical requirement for appropriate analgesia, alternative investigational approaches may be necessary. In this article we review the updated evidence for morphine in MI and outline novel strategies that may facilitate future investigation of this clinical dilemma. PMID- 27264229 TI - The "rise of the rule out": The SPECTer of cardiac stress imaging. PMID- 27264230 TI - Tackling cardiovascular disease in Hispanic/Latinos: Achieving 2020 Goals. PMID- 27264231 TI - Temporal trends of single-photon emission computed tomography myocardial perfusion imaging in patients without prior coronary artery disease: A 22-year experience at a tertiary academic medical center. AB - BACKGROUND: Between 1990 and 2006, there was a large national increase in utilization of single-photon emission computed tomography myocardial perfusion imaging (SPECT) for assessment of coronary artery disease (CAD). We aim to examine the trends of SPECT test results and patients' characteristics at Mayo Clinic Rochester. METHODS: Using the Mayo Clinic nuclear cardiology database, we examined all SPECT tests performed between January 1, 1991, and December 31, 2012, in patients without prior CAD. The study cohort was divided into 5 time periods: 1991-1995, 1996-2000, 2001-2005, 2006-2010, and 2011-2012. RESULTS: There were 35,894 eligible SPECT tests (mean age 62.5 +/- 12 years, 54% men). Annual utilization of SPECT increased significantly in 1992-2002 but then decreased without evidence of test substitution with stress echocardiography. There were modest changes in CAD risk factors over time. Testing of asymptomatic patients doubled (21.9% in 1991-1995 to 40% in 2006-2010) but later decreased to 33.6% in 2011-2012. Tests on patients with typical angina decreased dramatically (18.3% in 1991-1995 to 6.7% in 2011-2012). Summed stress score, summed difference score, and high-risk SPECT tests all decreased over time in both symptomatic and asymptomatic patients regardless of stress modality (exercise vs pharmacologic). CONCLUSIONS: In Mayo Clinic Rochester, annual SPECT utilization in patients without prior CAD increased in 1992-2002 but then decreased. Despite similar CAD risk factors and decreased utilization after 2003, more tests were low risk; summed stress score, summed difference score, and high-risk tests all decreased. Our findings confirm previous observations that SPECT was increasingly used in patients with a lower prevalence of CAD. PMID- 27264233 TI - Higher mortality among males in takotsubo cardiomyopathy. PMID- 27264232 TI - Cardiovascular health among diverse Hispanics/Latinos: Hispanic Community Health Study/Study of Latinos (HCHS/SOL) results. AB - BACKGROUND: Seven national 2020 Strategic Impact Goals for cardiovascular health (Life's Simple 7 [LS7]) estimates for major ethnic/racial groups are available, but not for diverse Hispanics/Latinos. Herein, we describe and examine LS7 profiles of diverse Hispanic/Latino groups. METHODS: HCHS/SOL (analytic n = 15,825; ages 18-74 years) data were used to estimate LS7 metrics. LS7 metrics were operationalized as Ideal, Intermediate, or Poor and indexed as an additive score. We calculated Hispanic/Latino group and sex-specific prevalence estimates for LS7 metrics and used survey-based regression models to examine (1) associations between LS7 scores and pertinent sociocultural characteristics and (2) relationships between LS7 scores and coronary heart disease, and stroke and transient ischemic attacks prevalence. RESULTS: Few HCHS/SOL participants met all 7 Ideal LS7 criteria (<1%), and a similarly small proportion did not meet any Ideal LS7 criteria (1.1%). We found significant variability in LS7 distributions between men and women and across HCHS/SOL Hispanic/Latino heritages. We also found a substantial sex-adjusted age gradient in LS7 cardiovascular health (ie, >=4 Ideal LS7s). Finally, higher Ideal LS7 scores were associated with decreased odds of both coronary heart disease and self-reported stroke/transient ischemic attack; these associations persisted after model covariate adjustments. CONCLUSIONS: Hispanic/Latino LS7s compared favorably with existing national estimates; however, we found areas for improvement. Several Hispanic/Latino LS7 strengths and weaknesses varied by sex and heritage, providing important information to guide targeted health promotion efforts toward achieving 2020 goals. PMID- 27264234 TI - Response to "Higher mortality among males in takotsubo cardiomyopathy". PMID- 27264236 TI - Rebuttal of critique of Progetto Vita survival data. PMID- 27264235 TI - The nonsense paradigm of rethinking the second link of the chain of survival: "if shock is not advised, wait and do nothing!" Aren't we condemning our cardiac arrest patients? PMID- 27264237 TI - The response to oxidative stress and metallomics analysis in a twin study: The role of the environment. AB - Inefficient response to oxidative stress has been associated with ageing and health risk. Metals are known to inhibit DNA repair and may modify the antioxidant response. How genetic variability and lifestyle factors modulate the response to oxidative stress is poorly explored. Our study aims to disentangle the contribution of genetics and environmental exposures to oxidative stress response using data from twin pairs. The non-enzymatic antioxidant capacity (NEAC), the repair capacity of 8-oxo-7,8-dihydroguanine (OGG activity) and the levels of 12 metals were measured in blood of 64 monozygotic and 31 dizygotic twin pairs. The contributions of genetic and environmental effects were assessed using standard univariate twin modelling. NEAC and OGG activity significantly decreased with age. Gender-, age- and body mass index-associated differences were identified for some metals. Principal Component Analysis identified two groups of metals whose levels in blood were highly correlated: As, Hg, Pb, Se, Zn and Al, Co, Cr, Mn, Ni. The environmental influence was predominant on OGG activity and NEAC variance whereas for most metals the best-fitting model incorporated additive genetic and unique environmental sources of variance. NEAC and OGG activity were both inversely correlated with blood levels of various metals. The inhibition of OGG activity by Cd was largely explained by smoking. Our data show a substantial role of environmental factors in NEAC and OGG activity variance that is not explained by twins' age. Exogenous environmental factors such as metals contribute to oxidative stress by decreasing NEAC and inhibiting repair of oxidatively-induced DNA damage. PMID- 27264238 TI - Melatonin prevents secondary intra-abdominal hypertension in rats possibly through inhibition of the p38 MAPK pathway. AB - Exogenous administration of melatonin has been demonstrated to down-regulate inflammatory responses and attenuate organ damage in various models. However, the salutary effect of melatonin against secondary intra-abdominal hypertension (IAH) remains unclear. This study sought to test the influence of melatonin on secondary IAH in a pathophysiological rat model and the underlying mechanisms involved. Before resuscitation, male rats underwent a combination of induced portal hypertension, applying an abdominal restraint device, and hemorrhaging to mean arterial pressure (MAP) of 40mmHg for 2h. After blood reinfusion, the rats were treated with lactated Ringer solution (LR) (30mL/h), melatonin (50mg/kg) +LR, and SB-203580 (10MUmol/kg)+LR. LR was continuously infused for 6h. MAP, the inferior vena cava pressure and urine output were monitored. Histopathological examination, immunofluorescence of tight junction proteins, and transmission electron microscopy were administered. Intestinal permeability, myeloperoxidase activity, malondialdehyde, glutathione peroxidase, and levels of TNF-a, IL-2, and IL-6, were assessed. The expression of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, translocation of nuclear factor kappa B subunit, signal transducers and activators of transcription and tight junction proteins were detected by Western blot. We found that melatonin inhibited the inflammatory responses, decreased expression of p38 MAPK, attenuated intestinal injury, and prevented secondary IAH. Moreover, administration of SB203580 abolished the increase in p38 MAPK and also attenuated intestinal injury. These data indicate that melatonin exerts a protective effect in intestine in secondary IAH primarily by attenuating the inflammatory responses which are in part attributable to p38 MAPK inhibition. PMID- 27264239 TI - The influence of foreign body surface area on the outcome of chronic osteomyelitis. AB - Reproducible animal models of osteomyelitis close to the clinical scenario are difficult to obtain as the animals either die shortly after inoculation of bacteria or the bone cures itself of infection. Additional materials used as foreign bodies offer increased chances for localized infection due to bacterial attachment and are closer to clinical pathology. Through in vivo experimentation we investigated here the influence of surface area of a series of foreign bodies on the final outcome of the animal model, in terms of reproducibility, survival rate and time necessary for onset of chronic disease. Stainless steel Kirschner wire segments, stainless steel balls and cotton meshes were employed for this purpose. The clinical, microbiological, radiological and histological results obtained were compared with the simple case where no foreign body was used. The follow-up period was 57days. The cotton meshes, which had the highest surface area, were observed to provide the best outcome, with the lowest disease onset time interval (of 1week earlier than the others), the highest survival (of 90%) and disease reproduction rate (90%). The only clinical pattern of the mesh group rabbits was short lived inflammation while the other rabbits presented also some other clinical signs such as rhinorrheas, abscesses, rush and/or dyspnea. Moreover, this model is the most suitable for further treatment studies, as the cotton meshes could be easily removed after disease onset, without any intervention on the bone. This is important, as the treatment would address the bacteria present within the bone parts (marrow, cortex, periosteum etc.) not those forming the biofilm. PMID- 27264240 TI - Smartphone application for emergency signal detection. AB - Currently, a number of studies focus on the study and design of new healthcare technologies to improve elderly health and quality of life. Taking advantage of the popularity, portability, and inherent technology of smartphones, we present an emergency application for smartphones, designated as knock-to-panic (KTP). This innovative and novel system enables users to simply hit their devices in order to send an alarm signal to an emergency service. This application is a complete and autonomous emergency system, and can provide an economic, reliable, and unobtrusive method for elderly monitoring or safety protection. Moreover, the simple and fast activation of KTP makes it a viable and potentially superior alternative to traditional ambient assisted living emergency calls. Furthermore, KTP can be further extended to the general population as well and not just be limited for elderly persons. The proposed method is a threshold-based algorithm and is designed to require a low battery power consumption. The evaluation of the performance of the algorithm in collected data indicates that both sensitivity and specificity are above 90%. PMID- 27264242 TI - The emerging roles of orphan nuclear receptors in prostate cancer. AB - Orphan nuclear receptors are members of the nuclear receptor (NR) superfamily and are so named because their endogenous physiological ligands are either unknown or may not exist. Because of their important regulatory roles in many key physiological processes, dysregulation of signalings controlled by these receptors is associated with many diseases including cancer. Over years, studies of orphan NRs have become an area of great interest because their specific physiological and pathological roles have not been well-defined, and some of them are promising drug targets for diseases. The recently identified synthetic small molecule ligands, acting as agonists or antagonists, to these orphan NRs not only help to understand better their functional roles but also highlight that the signalings mediated by these ligand-independent NRs in diseases could be therapeutically intervened. This review is a summary of the recent advances in elucidating the emerging functional roles of orphan NRs in cancers, especially prostate cancer. In particular, some orphan NRs, RORgamma, TR2, TR4, COUP-IFII, ERRalpha, DAX1 and SHP, exhibit crosstalk or interference with androgen receptor (AR) signaling in either normal or malignant prostatic cells, highlighting their involvement in prostate cancer progression as androgen and AR signaling pathway play critical roles in this process. We also propose that a better understanding of the mechanism of actions of these orphan NRs in prostate gland or prostate cancer could help to evaluate their potential value as therapeutic targets for prostate cancer. PMID- 27264241 TI - Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice. AB - Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system. PMID- 27264243 TI - Response to 'Cleaning up after carbapenemase-producing organisms'. PMID- 27264244 TI - Most international guidelines on prevention of healthcare-associated infection lack comprehensive recommendations for neonates and children. AB - International infection prevention and control (IPC) guidelines provide standardized recommendations for healthcare-associated infection (HCAI) prevention in adults, but often lack specific information about neonates and children. We reviewed ten international IPC/HCAI guidelines to identify paediatric-specific recommendations for HCAI prevention. Hand hygiene, bloodstream infection, ventilator-associated pneumonia, environmental control and outbreak management were frequently reported with recommendations applicable to children and newborns, but documents on catheter-associated urinary tract infection and surgical site infection were lacking. PMID- 27264246 TI - [Not Available]. PMID- 27264245 TI - An influence of the copy number of biosynthetic gene clusters on the production level of antibiotics in a heterologous host. AB - Streptomyces albus J1074 is a well-known host for heterologous expression of secondary metabolites. To further increase its potential and to study the influence of cluster multiplication, additional phiC31-attachment site was integrated into its genome using a system for transposon mutagenesis. Four secondary metabolite clusters were expressed in strains with different numbers of attachment sites, ranging from one to three copies of the site. Secondary metabolite production was examined and a new compound could be detected, purified and its structure was elucidated. PMID- 27264247 TI - A hydrophobic three-dimensionally networked boron-doped diamond electrode towards electrochemical oxidation. AB - A boron-doped diamond electrode with a three-dimensional network was fabricated on a mesh titanium substrate. Properties such as higher surface area, enhanced mass transfer and a hydrophobic surface endowed the prepared electrode with excellent electrochemical oxidation ability towards contaminants. PMID- 27264249 TI - Neuropsychological performance of young familial hypercholesterolemia patients. PMID- 27264250 TI - Reporting of secondary data analysis using routinely collected health data. PMID- 27264251 TI - Activated Protein C Resistance in Polycythemia Vera. AB - Activated protein C resistance is a result of a point mutation in factor V gene (Leiden mutation) and can be identified in approximately 50% of patients with thrombosis, making it an important risk factor for thrombosis. The aim of this study is to evaluate the role activated protein C resistance in the hypercoagulable state seen in polycythemia vera. We compared patients with polycythemia vera (n: 24) for increased risk of thromboembolism and activated protein C resistance, with the results of patients with chronic myelogenous leukemia (n: 27) and healthy control group (n: 52). Activated protein C resistance test and factor VIII activity was determined by an aPTT based test. Anticardiolipin antibodies IgG and IgM were also determined by ELISA. Leiden mutation was studied with polymerase chain reaction. Venous thromboses were observed in 12.5% and arterial thromboses in 41.6% of patients with polycythemia vera. Arterial thromboses were recognized in 7.4% of patients with chronic myelogenous leukemia. Activated protein C resistance was identified in 20.8% of patients with polycythemia vera and 14.8% with chronic myelogenous leukemia (versus 1.8% of healthy control subjects). The risk of thrombosis in patients with polycythemia vera was independent from the presence of activated protein C resistance. Leiden mutation was observed in only 1 patient out of 4 patients with chronic myelogenous leukemia who had activated protein C resistance, but not thrombosis. Factor VIII levels of patients with chronic myelogenous leukemia (158% +/- 14) were higher than healthy control subjects (99% +/- 15) (p< 0.05). Patients with activated protein C resistance in both groups had no seropositivity for anticardiolipin antibodies IgG and IgM. Activated protein C resistance and in some cases its association with Leiden mutation in polycythemia vera may not have a major role in the pathogenesis of thromboembolic complications of polycythemia vera. PMID- 27264252 TI - Thrombolysis of Acute Arterial Occlusion with rt-PA. AB - The use of thrombolytic agents to treat peripheral arterial occlusions is a new method. Despite its advantages, information about complications caused by the use of rt-PA and about its place in treatment is still incomplete. The aim of this study was to establish a dose range for rt-PA and to follow the patients with a protocol during and after thrombolysis. Between May 1999 to January 2000, 14 patients with symptoms of peripheral arterial occlusion came to Istanbul Medical Faculty Emergency Surgery Unit. The duration of ischaemia before their hospitalization took an average of 44 hours. (Range 3 hours-7 days). A pulse spray catheter was directed to the thrombus under angiographic control. Bolus injection of 5 mg of rt-PA was followed by 15 minutes of interval. The extent of thrombolysis was checked by angiography and then bolus injection of 5 mg of rt- PA was repeated. After angiographic control, patients having insufficient thrombolysis, received 0.05 mg/kg/hour of infusion for 12 hours. At the end of 12 hours, thrombolytic treatment ended with a control angiography. A thromboembolectomy operation was made to patients still having an occlusion after thrombolysis. To avoid re-occlusions, all of the patients received 1.5 mg/kg/day low molecular weight heparin (enoxaparin) for 1 week. At the end of thrombolysis, 9 patients had complete lysis. A patient, having an occlusion in superior mesenteric artery had 60% recanalisation. 2 patients (14%) having 90% stenosis, needed a balloon angioplasty besides thrombolysis, and both of them had complete reperfusion. 2 patients (14%) needed a thromboembolectomy operation due to insufficient thrombolysis. 2 patients (14%) had a minor bleeding after thrombolytic treatment. After thrombolysis, 2 patients (14%) had a stroke. There were no amputations. 1 of the patients having a stroke, died 2 days after thrombolytic treatment 1 patient died due to myocardial infarction during thrombolysis. 1 patient (7%) died due to diabetic coma on the 20th day. Acute myocardial infarction was the cause of death in 1 patient on the 25th day. In conclusion pulse spray thrombolysis with rt-PA is safe and efficient. Moreover there is a reduction in complications and need for surgical procedure. The recent problem is to find the optimum dosages for the best thrombolysis and for least complications. PMID- 27264253 TI - Defective Function of Peripheral Blood Monocytes from Patients with Non-Hodgkin's Lymphoma. AB - The aim of the study was to analyze the function of peripheral blood monocytes from patients with Non-Hodgkin's lymphoma before and after incubation with zymosan and indomethacin. Peripheral blood samples were collected from 28 patients with malignant lymphoma (13 males and 15 females with age range 20-65) years. Their clinical record and pathologic material were reviewed. The control group consisted of 17 normal subjects, (9 men and 8 women) of age range of 20-45 years. The following investigations were carried out in all patients: Bactericidal activity against Escherichia coli. Level of superoxide anion and Chemiluminescence's Technique for analysis of oxygen metabolite Results. The mean bactericidal indices of E. coli by peripheral blood monocytes without indomethacin were 56.75 (SD +/- 10.5) in control group at 60 minutes and it was 36.88% (SD +/- 11.3) in Non-Hodgkin's lymphoma patients. The level of INT was greater in healthy control than NHL-patients. The improvement after addition of zymosan was significant in all groups. The peak generation of chemiluminescence in Non-Hodgkin lymphoma patients was 11256 x 10-3 CPM at 20 minutes and in healthy controls 16575 x 10-3 CPM at 5 minutes and after incubation with zymosan and indomethacin were 13843 x 10-3 CPM at 5 minutes in NHL patients and 16312 x 10-3 CPM in healthy controls. The time of appearance of CL peak improved in Non Hodgkin's lymphoma patients (p< 0.01) but there is no difference in the time of CL peak of the healthy controls. PMID- 27264248 TI - The role of basal forebrain cholinergic neurons in fear and extinction memory. AB - Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral amygdala (BLA) is critical for neural function and synaptic plasticity in these brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp), and BLA has also been implicated in fear and extinction memory. This finding raises the possibility that basal forebrain (BF) cholinergic neurons, the predominant source of acetylcholine in these brain regions, have an important role in mediating fear and extinction memory. While empirical studies support this hypothesis, there are interesting inconsistencies among these studies that raise questions about how best to define the role of BF cholinergic neurons in fear and extinction memory. Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA are critical for fear memory and contextual fear extinction memory. NBM cholinergic neurons that project to the neocortex are critical for cued and contextual fear conditioned suppression, but are not critical for fear memory in other behavioral paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear memory formation. Medial septum and diagonal band of Broca cholinergic neurons are critical for contextual fear memory and acquisition of cued fear extinction. Thus, even though the results of previous studies suggest BF cholinergic neurons modulate fear and extinction memory, inconsistent findings among these studies necessitates more research to better define the neural circuits and molecular processes through which BF cholinergic neurons modulate fear and extinction memory. Furthermore, studies determining if BF cholinergic neurons can be manipulated in such a manner so as to treat excessive fear in anxiety disorders are needed. PMID- 27264254 TI - Oral Health Status in Children with Acute Lymphoblastic Leukemia and Lymphoma. AB - We evaluated the oral health status of 85 acute lymphoblastic leukemia (ALL)/lymphoma pediatric patients who received remission-induction and maintenance chemotherapy and 85 age and sex-matched healthy children with the criteria of World Health Organization (WHO) and to determine the prevalence and distribution of dental problems in order to constitute preventive dentistry precautions in this study. The gingival tissues were scored with Community Index of Periodontal Treatment Necessity (CPITN) and dmf-t and DMF-T indices were used for caries evaluation. In the study group, malocclusion was found in 24 patients (28.2%). CPITN was scored as follows in the study group; 11% of the patients had healthy gingiva (Grade 0), the presence of plaque (Grade I) 79% of the patients, the presence of calculus (Grade II) 10% of patients were observed. Nevertheless, mucositis was found with various grades in 9 patients who received chemotherapy. Decayed teeth were found in the 76 patients and in 45 healthy children. 91.7% of patients and 52.9% of children needed dental treatment were determined. The DMF-T and dmf-t scores showed that ALL/lymphoma patients had more decayed and needed more dental treatment, missing or filled teeth both in their deciduous (p< 0.001) and permanent (p< 0.05) dentition when compared to systemically healthy children. PMID- 27264255 TI - Relationship Between Leptin Levels and Body Indexes in Patients with Haematologic Malignancy. AB - Leptin is a recently found hormone regulating body weight. In human obesity, this weight-regulating hormone level is in a positive correlation with FMI (fat mass index) and BMI (body mass index). In this study, we aimed to investigate the relation between serum leptin levels and BMI, PF (percentage fat), LMI (lean mass index), FMI and some other parameters of patients with haematologic malignant diseases. Fourty-four patients with haematologic malignant diseases and 25 healthy control group were taken into the study. In the comparison, there were no significant difference between the PF and FMI values of both groups, while the mean BMI and LMI values of the control group were significantly higher than that of the patient group. There was a positive correlation between leptin levels and BMI and FMI among parameters studied in our control group, whereas we couldn't demostrate any such correlation in patient group. We estimate that the alteration may be due to disturbances in the feed back mechanism developing in patient with haematologic malignancy. PMID- 27264256 TI - Bernard-Soulier Syndrome Like Platelet Defect in a Patient with Noonan Syndrome; A Case Report. AB - Noonan's Syndrome (NS) is characterized by dismorphic facial features, short stature, short or webbed neck, congenital heart defects and testicular abnormalities. Various bleeding disorders in Noonan Syndrome have been reported. Bernard-Soulier Syndrome (BSS) is a rare congenital bleeding disorder characterized by thrombocytopenia and giant platelets. There is not any reported case of Noonan syndrome associated with BSS in literature. We report here a four year-old male patient with Noonan Syndrome and BSS like platelet defect. PMID- 27264257 TI - Homozygous beta-Thalassemia Associated with Familial Mediterranean Fever in a Turkish Patient. AB - We report here a beta- thalassemia major case (homozygous IVS-1-110 G-A) associated with Familial Mediterranean Fever (FMF) (homozygous 694 Met-Val). Our patient's clinical course revealed a possible synergistic effect between colchicine and desferrioxamine (DFO) However, this could be a only a coincidence, as under colchicine therapy, fever attacks may appear, this may be the topic of a further investigation. PMID- 27264258 TI - Hemoglobin Lepore Boston in a Turkish Family. AB - An abnormal hemoglobin was detected in a Balkan immigrant Turkish family. Erythrocyte morphology was similar to beta-thalassemia trait. Molecular analysis showed that the abnormal hemoglobin was Hemoglobin LeporeBoston. All affected family members were in heterozygote state and asymptomatic. PMID- 27264259 TI - A Case with Micromegakaryocytes. AB - A boy with no previous history of bleeding presented with ecchymoses and splenomegaly. He was followed up for thrombocytopenia and micromegakaryocytes for 20 months till clinically malignancy was diagnosed. Micromegakaryocytes must always be treated with suspicion, as they may provide an important clue for dyshematopoesis. KEY WORDS: Micromegakaryocytes, Leukemia, Dismegakaryopoesis. PMID- 27264260 TI - Consecutive IL-2 and IFN-a2a Maintenance in a Patient with Acute Non lymphoblastic Leukemia and Renal Cell Cancer. AB - Over the last few years, the use of interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells have been found to be effective in the treatment of some solid tumours and acute myeloid leukemia. Our patient was initially diagnosed as having bilateral synchronous renal cell cancer (RCC) and underwent nephrectomy. Approximately two years after the operation he developed leukopenia without any sign of residual renal cell cancer. Bone marrow examination revealed acute myeloblastic leukemia (AML). IL-2 following IFN-a2a was used as a maintenance therapy after a standard remission induction and a consolidation therapy. Our patient has been still disease free for 58 months after the diagnosis of AML and 71 months after the diagnosis renal cell cancer. Review of the literature showed that this is the first case who has both RCC and AML and was treated successfully with IL-2 and IFN-a2a. PMID- 27264261 TI - Images in Haematology. PMID- 27264263 TI - Idiopathic Hypereosinophilic Syndrome with Hepatic Tumoral Lesions. PMID- 27264262 TI - Chronic Myeloid Leukemia Associated with Ebstein's Anomaly. PMID- 27264264 TI - Cyclosporine A sensitizes human non-small cell lung cancer cells to gefitinib through inhibition of STAT3. AB - The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically prolonged the overall survival of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, but the presence of primary or acquired resistance eventually leads to therapeutic failure. Thus, how to improve the efficacy and reverse the resistance to EGFR-TKIs remains a significant challenge. In this study, we found that CsA significantly augmented the anti-cancer effect of gefitinib in EGFR-TKI-sensitive and -resistant NSCLC cells. Mechanistically, CsA promoted gefitinib-induced apoptosis through inhibition of the STAT3 pathway. Similar with the function of CsA, siRNAs against STAT3 also enhanced gefitinib induced apoptosis in multiple lung cancer cells. Xenograft studies further demonstrated that CsA promoted the anti-cancer activity of gefitinib on lung cancer cells through inhibition of STAT3. Moreover, NSCLC patients with high levels of phosphorylated STAT3 (Y705) showed a significantly poorer therapeutic response to EGFR-TKIs. This study provides preclinical evidence that the combination of CsA or a STAT3 inhibitor with EGFR-TKIs is a promising approach to improve the efficacy of EGFR-TKIs for the treatment of patients with advanced NSCLC. PMID- 27264266 TI - Laparoscopic surgery for colorectal cancer: advantages and challenges. PMID- 27264265 TI - Extensive molecular analysis suggested the strong genetic heterogeneity of idiopathic chronic pancreatitis. AB - Rationale: Genetic features of Chronic Pancreatitis (CP) have been extensively investigated mainly testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. Objectives: 80 patients with Idiopathic CP were investigated using Next Generation Sequencing approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen; modifier genes of Cystic Fibrosis phenotype; pancreatic secretion and ion homeostasis; Calcium signalling and zymogen granules exocytosis; autophagy; autoimmune pancreatitis related genes. Results: We detected mutations in 34 out of 70 genes examined; 64/80 patients (80.0%) were positive for mutations in one or more genes, 16/80 patients (20.0%) had no mutations. Mutations in CFTR were detected in 32/80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38/64 patients positive for mutations showed variants in two or more genes (59.3%). Conclusions: Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in chronic pancreatitis and that trans-heterozygosity may predispose to the idiopathic CP phenotype. PMID- 27264267 TI - Docetaxel plus gemcitabine versus gemcitabine in elderly patients with advanced non-small cell lung cancer and use of a geriatric assessment: Lessons from a prematurely closed Hellenic Oncology Research Group randomized phase III study. AB - OBJECTIVES: To compare first-line treatment with docetaxel plus gemcitabine (DG) versus gemcitabine (G) in elderly patients with advanced/metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with inoperable stage IIIB/IV NSCLC, >=70years, with an ECOG performance status (PS) of 0-2 were enrolled. Patients were stratified by PS and disease stage and randomized to either DG (docetaxel 30mg/m2 plus gemcitabine 900mg/m2 i.v.) or G (gemcitabine 1200mg/m2 i.v.) on days 1 and 8, every 3weeks. The study's primary end-point was overall survival (OS). RESULTS: In this prematurely closed study, 106 patients with a median age of 75years (range, 70-92) were enrolled (DG: n=54; G: n=52); 77 (73%) had stage IV disease and 18 (17%) a PS of 2. There was no difference in terms of median OS (14.6 vs 12.2months; p=0.121), progression-free survival (PFS) (3.4 vs 2.6months; p=0.757) and overall response rate (26.0% vs 15.4%; p=0.233) between DG and G arm, respectively. Patients with an Instrumental Activities of Daily Living (IADL) score<7 had significantly lower median OS (7.6 vs 15.4months; p=0.002) and median PFS (1.7 vs 4.4months; p=0.009) than patients with higher IADL score. The regimens were well tolerated with no significant difference in severe toxicity. CONCLUSION: DG and G demonstrated comparable efficacy in elderly patients with NSCLC and high IADL score was correlated with superior clinical outcome. PMID- 27264268 TI - Mutant B-Raf Kinase Inhibitors as Anticancer Agents. AB - The Ras/Raf/MEK/ERK signaling pathway involves various kinases in which each kinase is associated with one another through signals and regulates cell proliferation, differentiation and apoptosis. This pathway is dysregulated almost in all cancers due to the amplification and genetic mutation of various components of the pathway. The genetic mutations have been reported to cause drug resistance to the current chemotherapy of melanomas. B-Raf is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Therefore, mutant B-Raf kinase may be a promising therapeutic target for the development of novel anticancer drugs. Many BRAF inhibitors discovered during the last decade showed promising anticancer activity, especially on tumors that harbor BRAFV600E mutations. Currently, vemurafenib and dabrafenib are USFDA approved drugs used as B-Raf inhibitors. Few drugs which are under clinical development phases such as LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265 etc. pave the path for further designing of B-Raf inhibitors. The present review focuses primarily on the Ras/Raf/MEK/ERK signaling pathway with mutant B-Raf as a therapeutic target for anticancer drug development. The essential pharmacophoric features of B-Raf inhibitors, their structure activity relationships (SARs) and molecules under clinical trials have been highlighted. PMID- 27264269 TI - Rapid assessment of knowledge, attitudes, practices, and risk perception related to the prevention and control of Ebola virus disease in three communities of Sierra Leone. AB - BACKGROUND: The recent outbreak of the Ebola virus disease (EVD) in Sierra Leone has been characterized by the World Health Organization as one of the most challenging EVD outbreaks to date. The first confirmed case in Sierra Leone was a young woman who was admitted to a government hospital in Kenema following a miscarriage on 24 May 2014. On 5 January 2015, intensified training for an EVD response project was initiated at the medical university of Sierra Leone in Jui. To understand the knowledge, attitudes, practices, and perceived risk of EVD among the public, especially after this training, a rapid assessment was conducted from 10 to 16 March 2015. METHODS: Interviews were conducted with 466 participants based on questionnaires that were distributed from 10 to 16 March 2015 by cluster sampling in three adjacent communities, namely Jui, Grafton, and Kossoh Town, in the Western Area Rural District of Sierra Leone. RESULTS: It was found that knowledge about EVD was comprehensive and high. Positive attitude towards prevention was found to be satisfactory. Nearly all participants knew the reporting phone number 117 and had reported some change in behavior since learning about Ebola. More than half (62 %) of the participants had a history of travelling to urban areas, which increases the risk of infection. The multivariable logistic regression analysis showed that community and occupation were variables associated with perceived risk of EVD. CONCLUSIONS: Our study showed that community level social mobilization and community engagement were an effective strategy in the special context. PMID- 27264270 TI - Critical length scale controls adhesive wear mechanisms. AB - The adhesive wear process remains one of the least understood areas of mechanics. While it has long been established that adhesive wear is a direct result of contacting surface asperities, an agreed upon understanding of how contacting asperities lead to wear debris particle has remained elusive. This has restricted adhesive wear prediction to empirical models with limited transferability. Here we show that discrepant observations and predictions of two distinct adhesive wear mechanisms can be reconciled into a unified framework. Using atomistic simulations with model interatomic potentials, we reveal a transition in the asperity wear mechanism when contact junctions fall below a critical length scale. A simple analytic model is formulated to predict the transition in both the simulation results and experiments. This new understanding may help expand use of computer modelling to explore adhesive wear processes and to advance physics-based wear laws without empirical coefficients. PMID- 27264271 TI - An Arab registry for type 1 diabetes: global benefits for type 1 diabetes patients. AB - BACKGROUND: The Arab world encompasses twenty-two Arabic-speaking countries, where the rate of consanguinity can exceed 50%. Type 1 diabetes (T1D), a chronic disorder that requires lifelong treatment, is believed to be largely due to genetic predisposition. The objective of this review is to discuss the benefits of establishing an Arab population-based diabetes registry, which will provide a reference for T1D prevalence and incidence. METHODS: An online search was carried out through various websites, including PubMed, government, hospitals and health ministries of the 22 Arab countries to understand the reporting activities of diabetes in the Arab world. RESULTS AND CONCLUSION: The prevalence and incidence of T1D is variable among Arabs, with the availability of only a few national/regional diabetes registries to support diabetes research, provide reliable data, and to cope with the widespread threat of this disease. Hence, the need of establishing a population based Arab diabetes registry. PMID- 27264272 TI - Antibody-free detection of protein phosphorylation using intrinsic peroxidase like activity of platinum/carbon dot hybrid nanoparticles. AB - Platinum and carbon dot hybrid nanomaterials are prepared for visualized detection of phosphoproteins without the need for antibodies or enzymes. This new strategy can be used for colorimetric detection of phosphoproteins induced by protein kinase as well as protein phosphorylation sites on cell membranes. PMID- 27264274 TI - The G allele in IL-10-1082 G/A may have a role in lowering the susceptibility to panic disorder in female patients. AB - BACKGROUND: Immune system activation is involved in the pathophysiology of panic disorder (PD). We investigated INF-gamma+874 A/T, TNF-alpha-308 G/A, and IL-10 1082 G/A single nucleotide polymorphisms (SNPs) to determine their association with PD. METHOD: This study enroled 135 PD patients and 135 healthy controls. INF gamma+874 A/T (rs2430561), TNF-alpha-308 G/A (rs1800629), and IL-10-1082 G/A (rs1800896) were genotyped. RESULTS: There were no differences in genotypes or allele frequencies between the patient and control groups, regardless of accompanying agoraphobia. However, for female patients, the G allele frequency in IL-10 SNP was higher in the control group than in the patient group. Additionally, the female control group had a higher frequency of the A/G and G/G genotype in the IL-10 SNP than the female patient group. CONCLUSION: We suggest that the G allele in IL-10-1082 G/A might have a role in reducing the manifestations of PD in female patients. Further studies are needed to extend and confirm our findings. PMID- 27264273 TI - Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas. AB - Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 MUm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery. PMID- 27264275 TI - Synthesis and structural analyses of phenylethynyl-substituted tris(2 pyridylmethyl)amines and their copper(ii) complexes. AB - Three new tris(2-pyridylmethyl)amine-based ligands possessing phenylethynyl units have been prepared using Sonogashira couplings and substitution reactions. Copper(ii) complexes of those tetradentate ligands have also been synthesized. Solid-state structures of the six new compounds have been determined by single crystal X-ray diffraction analyses. Examination of the molecular structures of the ligands revealed the expected triangular geometries with virtually undeformed carbon-carbon triple bonds. While the tertiary nitrogen of the free ligands seem to be prevented from participation in supramolecular non-covalent interactions by the pyridyl hydrogen at the 3-position, the pyridyl nitrogens play a crucial role in the packing mode of the crystal structure. The nitrogens form weak hydrogen bonds, varied in length between 2.32 and 2.66 A, with the pyridyl hydrogen of its neighbouring molecule. The [NH-C] contacts enforce one-dimensional columnar assemblies on ligands that organize into wall-like structures, which in turn assemble into three-dimensional structures through CH-pi interactions. Structural analyses of Cu(ii) complexes of the ligands revealed propeller-like structures caused by steric crowding of three pyridine ligands. The copper complexes of the ligands having three phenylethynyl substituents showed a remarkably deformed carbon-carbon triple bond enforced by a steric effect of the three phenyl groups. Most significantly, a total of seventy non-covalent interactions, classified into twelve types of hydrogen-involving short contacts, were identified in this study. The phenylethynyl substituent participated in forty-two interactions as a hydrogen bond acceptor, and its role was more distinctive in the crystal structures of the Cu(ii) complexes. PMID- 27264276 TI - C-reactive protein and cardiovascular disease. PMID- 27264277 TI - Ability of modern distal tibia plates to stabilize comminuted pilon fracture fragments: Is dual plate fixation necessary? AB - OBJECTIVES: The purpose of this study was to examine the screw trajectory of ten commercially available distal tibia plates and compare them to common fracture patterns seen in OTA C type pilon fractures to determine their ability to stabilize the three most common fracture fragments while buttressing anterolateral zones of comminution. HYPOTHESIS: We hypothesized that a single plate for the distal tibia would fail to adequately stabilize all three main fracture fragments and zones of comminution in complex pilon fractures. METHODS: Ten synthetic distal tibia sawbones models were used in conjunction with ten different locking distal tibia plate designs from three manufacturers (Depuy Synthes, J&J Co, Paoli, PA; Smith & Nephew, Memphis, TN; and Stryker, Mawa, NJ). Both medial and anterolateral plates from each company were utilized and separately applied to an individual sawbone model. Three implants allowing variable angle screw placement were used. The location of the locking screws and buttress effect 1cm above the articular surface was noted for each implant using axial computed tomography (CT). The images were then compared to a recently published "pilon fracture map" using an overlay technique to establish the relationship between screw location and known common fracture lines and areas of comminution. Each of the three main fragments was considered "captured" by a screw if it was purchased by at least two screws thereby controlling rotational forces on each fragment. RESULTS: Three of four anterolateral plates lacked stable fixation in the medial fragment. Of the 4 anterolateral plates used, only the variable angle anterolateral plate by Depuy Synthes captured the medial fragment with two screws. All four anterolateral plates buttressed the area of highest comminution and had an average of 1.25 screws in the medial fragment and an average of 3 screws in the posterolateral fragment. All five direct medial plates had variable fixation within anterolateral and posterolateral fragments with an average of 1.8 screws in the anterolateral fragment and an average of 1.3 screws in the posterolateral fragment. The Depuy Synthes variable angle anterolateral plate allowed for fixation of the medial fragment with two screws while simultaneously buttressing the zone of highest comminution and capturing both the anterolateral and posterolateral fragments with five and three screws respectively. The variable angle anteromedial plate by Depuy Synthes captured all three main fracture fragments but it did not buttress the anterolateral zone of comminution. CONCLUSION: In OTA 43C type pilon fractures, 8 out of 10 studied commercially available implants precontoured for the distal tibia, do not adequately stabilize the three primary fracture fragments typically seen in these injuries. Anterolateral plates were superior in addressing the coronal primary fracture line across the apex of the plafond, and buttressing the zone of comminution. None of the available plates can substitute for an understanding of the fracture planes and fragments typically seen in complex intra-articular tibia fractures and the addition of a second plate is necessary for adequate stability. LEVEL OF EVIDENCE: Level IV. PMID- 27264278 TI - Prospects of medium specific activity (177) Lu in targeted therapy of prostate cancer using (177) Lu-labeled PSMA inhibitor. AB - Targeted radionuclide therapy using (177) Lu-labeled peptidomimetic inhibitor of prostate specific membrane antigen (PSMA) viz. PSMA-617 is emerging as one the most effective strategies for management of metastatic prostate cancer, which is one of the leading causes of cancer related death. The aim of the present study is to develop a robust and easily adaptable protocol for formulation of therapeutic dose of (177) Lu-PSMA-617 at hospital radiopharmacy using moderate specific activity (177) Lu available at an affordable cost. Extensive radiochemical studies were performed to optimize the required [PSMA-617] / [Lu] ratio and other parameters to formulate 7.4 GBq dose of (177) Lu-PSMA-617. Based on these, 7.4 GBq therapeutic dose of (177) Lu-PSMA-617 was formulated by incubating 160 ug of PSMA-617 with indigenously produced (177) LuCl3 (555 GBq/ug specific activity of (177) Lu) at 90 degrees C for 30 min. The radiochemical purity of the formulation was 98.3 +/- 0.6% (n = 7) which was retained to the extent of >95% after 7 d in normal saline at room temperature and >96% after 2 d in human serum at 37 degrees C. Preliminary clinical studies showed specific targeting of the agent in the lesion sites and similar physiological distribution as in diagnostic (68) Ga-PSMA-11 PET scans performed earlier. The developed optimized protocol for formulating therapeutic dose of (177) Lu-PSMA-617 could be useful for large number of nuclear medicine therapy clinics across the world having access to moderate specific activity (177) Lu at an affordable cost. PMID- 27264279 TI - Synthesis and in vitro bone cell activity of analogues of the cyclohexapeptide dianthin G. AB - The cyclohexapeptide natural product dianthin G promotes osteoblast (bone-forming cell) proliferation in vitro at nanomolar concentrations, and is therefore considered a promising candidate for the treatment of osteoporosis. An N(alpha) methyl amide bond scan of dianthin G was performed to probe the effect of modifying amide bonds on osteoblast proliferation. In addition, to provide greater structural diversity, a series of dicarba dianthin G analogues was synthesised using ring closing metathesis. Dianthin G and one novel dicarba analogue increased the number of human osteoblasts and importantly they did not increase osteoclast (bone-resorbing cell) differentiation in bone marrow cells. PMID- 27264280 TI - Different desferrioxamine usage in the patients with thalassemia major: a cost effect analysis. AB - Regular desferrioxamine (DFO) usage in patients with thalassemia major (TM) ameliorates hepatic, cardiac and endocrine dysfunction, improves growth and sexual maturation and prolongs survival. The difficulties of administering DFO with classic pumps are well known. The aim of this study was to compare the iron accumulation and cost effects between the continuous 48 hours infusion of DFO with infusor pump and the intermittent 40 hours infusion with classic pump in patients with TM. A total of 54 patients with TM were divided to two groups, first group includes 27 patients (18 female, 9 male) aged between 5.5 and 20.5 years, and were infused a total of 100 mg/kg DFO with infusor in 48 hours. Second group includes 27 patients (18 female, 9 male) aged between 6 and 22 years, were infused a total of 200 mg/kg DFO in 4 days with an intermittent infusions for about in 40 hours. After one year of treatment, the patients were compared from a clinical view point and cost of medical treatment. No statistical difference was found between infusor pump and classic pump in terms of cost-effectiveness. PMID- 27264281 TI - Body mass index in children with beta-thalassemia major. AB - Underweight or low body mass index (BMI) is associated with developing many health problems. Despite the presence of many growth abnormalities in patients with beta thalassemia major, BMI has not been adequately studied. All of the thalassemic patients under 18 years of age, registered in thalassemia center of Shiraz, were studied. Medical history was taken and complete physical examination was done. BMI (weight/height2) at different ages was calculated and compared with standardized percentile curves of BMI for children and adolescents. BMI less than 10th percentile for sex and age was observed in 12.4% of thalassemic patients under 10 years of age and in 46.5% of patients above 10 years of age (p< 0.000001). Also the observed difference between girls and boys, specially when they are more than 10 years of age is significant (p< 0.000001). Underweight is a common finding in patients with beta-thalassemia major specially when they are older than 10 years of age. This is possibly because of the occurrence of multiple endocrinopathies and also the presence of under-nutrition in these patients. So growth should be monitored routinely at regular intervals in order to detect any decline in growth velocity and also any derangement in BMI to establish an appropriate protocol for investigation and treatment. PMID- 27264283 TI - Evaluation of neutrophil functions in obstructive jaundice patients. AB - Jaundiced surgical patients have a high incidence of post-operative complications and sepsis is a major factor in the high mortality and morbidity of obstructive jaundice patients after surgery. Cachexia and immune suppression have been shown to be involved in this post-operative complications. Since neutrophils dysfunction is recognized in recurrent infections in general, the aim of the study was to evaluate the functional status of neutrophils in jaundiced patients. Phagocytosis, bactericidal activity, mitogenic stimulation of T-lymphocytes and myeloperoxidase activity were measured in the neutrophils isolated from obstructive jaundice patients. Phagocytic and bactericidal activities of neutrophils were significantly low in obstructive jaundice patients. The number of cells stained for myeloperoxidase was significantly low in obstructive jaundice patients. There was a high level of stimulation and proliferation exhibited by lymphocytes when challenged by conconavalin-A and lipopolysaccharide in vitro. The functional impairment of neutrophils may be responsible for the immunity alteration in obstructive jaundice patients and this may be responsible for the post-operative complications in obstructive jaundiced patients. PMID- 27264282 TI - ABO blood group prevalence in spontaneously repeated abortion. AB - The relation of ABO blood groups to disease is well established. In 1943, Levine had identified ABO incompatibility as a cause of early abortions and stillbirths. From this time onwards numerous workers produced data suggesting, mainly on the grounds of a deficiency of A children, and an excess of abortions, in the families of O women married to A men, that the A fetuses produced by such mating were especially liable to be aborted. Seventy-nine couples from Pune city (India), suffering from repeated abortion have been investigated for the ABO blood groups system to find out the frequency of ABO blood group phenotypes and ABO incompatibility as a cause of abortion. In husband group maximum number of individuals had blood group A. In wife group, blood group B showed the highest number of individuals. In mixed group 154 patients have been tested and out of these, again blood group A, shows the highest number of individuals. Blood group "A" and "AB" was significantly higher in individual and mixed groups as compared with normal groups in this study. ABO blood group of husband/wife mating was also determined, the analysis of husband/wife joint "ABO" blood group distribution in these couples, shows an excess of joint "A/B" blood groups in couples as compared with expected proportions assuming random mating. This study came to a conclusion that there is a clear increase in number of individuals for blood group A and AB in-patients with repeated abortion, and this factor may need to pay more attention in future investigations. It is possible that incompatibility of the antigens present in red blood cell membrane of husband/wife may play some role in abortion. PMID- 27264284 TI - Diffuse alveolar hemorrhage associated with thrombotic thrombocytopenic purpura after allogeneic bone marrow transplantation. AB - Alveolar hemorrhage is an early complication after bone marrow transplantation (BMT) and often associated with inflammatory pulmonary processes. We present a case of diffuse alveolar hemorrhage associated with BMT associated thrombotic thrombocytopenic purpura (BMT-TTP). An 18-years-old man with acute myeloid leukaemia (FAB; M5) underwent ABO incompatible BMT from his HLA-identical sister. On the 37th day of BMT, BMT-TTP was diagnosed with the occurrence of red cell fragmentation and rise in serum lactic dehydrogenase (LDH) level with severe sudden decrease in hemoglobin and platelet levels. Cyclosporine A (CsA) was ceased and plasma infusion with plasma exchange was started. On the 42nd day of BMT, the diagnosis of diffuse alveolar hemorrhage was made by the clinical, bronchoscopic and bronchoalveolar lavage fluid findings. Alveolar hemorrhage among patients with BMT-TTP has been scarce reported. These two complications may be regarded as related, as small vessel injury is a central feature in both and they may share aetiological and pathogenetic factors. PMID- 27264285 TI - Hereditary factor VII deficiency in two siblings: two different clinical presentation. AB - Factor VII (FVII) deficiency is a rare bleeding disorder with a highly variable hemorrhagic predisposition. It is transmitted as an autosomal recessive and plays an important role in the initiation of blood coagulation forming a complex with tissue factor which activates FIX, FX and FVII zymogen. Prolonged prothrombin time with normal partial thromboplastin time indicates FVII deficiency. For the definitive diagnosis, the specific plasma FVII level should be investigated. FVII deficiency is expressed in different ways and leads to various clinical pictures. I reported two siblings with hereditary factor VII deficiency whose clinical presentations were different. PMID- 27264286 TI - Images in Hematology. PMID- 27264287 TI - Prevalence of hepatitis C infection in lymphoma patients in a Turkish center. PMID- 27264288 TI - Should carba mix be reintroduced into the European baseline series? PMID- 27264289 TI - Contact dermatitis caused by panthenol used for aftercare treatment of a new tattoo. PMID- 27264290 TI - Contact dermatitis caused by turmeric in a massage oil. PMID- 27264292 TI - A rare case of occupational contact urticaria syndrome caused by meranti wood dust. PMID- 27264291 TI - Deflazacort hypersensitivity: a difficult-to-manage case of systemic allergic dermatitis and literature review. PMID- 27264293 TI - Benzyl alcohol allergy mimicking corticosteroid allergy. PMID- 27264294 TI - Is p-phenylenediamine (PPD) a better marker of contact allergy to PPD-based hair dyes than its salt PPD dihydrochloride? PMID- 27264295 TI - Is there a good in vivo method to show whether gloves are sufficiently protective when a nail technician is exposed to (meth)acrylates? An in vivo pilot study. PMID- 27264296 TI - A Microbead Supported Membrane-Based Fluorescence Imaging Assay Reveals Intermembrane Receptor-Ligand Complex Dimension with Nanometer Precision. AB - Receptor-ligand complexes spanning a cell-cell interface inevitably establish a preferred intermembrane spacing based on the molecular dimensions and orientation of the complexes. This couples molecular binding events to membrane mechanics and large-scale spatial organization of receptors on the cell surface. Here, we describe a straightforward, epi-fluorescence-based method to precisely determine intermembrane receptor-ligand dimension at adhesions established by receptor ligand binding between apposed membranes in vitro. Adhesions were reconstituted between planar and silica microbead supported membranes via specific interaction between cognate receptor/ligand pairs (EphA2/EphrinA1 and E-cadherin/anti-E cadherin antibody). Epi-fluorescence imaging of the ligand enrichment zone in the supported membrane beneath the adhering microbead, combined with a simple geometrical interpretation, proves sufficient to estimate intermembrane receptor ligand dimension with better than 1 nm precision. An advantage of this assay is that no specialized equipment or imaging methods are required. PMID- 27264309 TI - Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium. AB - Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn't induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates. PMID- 27264310 TI - AMPA Receptor Plasticity in Accumbens Core Contributes to Incubation of Methamphetamine Craving. AB - BACKGROUND: The incubation of cue-induced drug craving in rodents provides a model of persistent vulnerability to craving and relapse in human addicts. After prolonged withdrawal, incubated cocaine craving depends on strengthening of nucleus accumbens (NAc) core synapses through incorporation of Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (CP-AMPARs). Through metabotropic glutamate receptor 1 (mGluR1)-mediated synaptic depression, mGluR1 positive allosteric modulators remove CP-AMPARs from these synapses and thereby reduce cocaine craving. This study aimed to determine if similar plasticity accompanies incubation of methamphetamine craving. METHODS: Rats self administered saline or methamphetamine under extended-access conditions. Cue induced seeking tests demonstrated incubation of methamphetamine craving. After withdrawal periods ranging from 1 to >40 days, rats underwent one of the following procedures: 1) whole-cell patch clamp recordings to characterize AMPAR transmission, 2) intra-NAc core injection of the CP-AMPAR antagonist 1-naphthyl acetyl spermine followed by a seeking test, or 3) systemic administration of a mGluR1 positive allosteric modulator followed by a seeking test. RESULTS: Incubation of methamphetamine craving was associated with CP-AMPAR accumulation in NAc core, and both effects were maximal after ~1 week of withdrawal. Expression of incubated craving was decreased by intra-NAc core 1-naphthyl acetyl spermine injection or systemic mGluR1 positive allosteric modulator administration. CONCLUSIONS: These results are the first to demonstrate a role for the NAc in the incubation of methamphetamine craving and describe adaptations in synaptic transmission associated with this model. They establish that incubation of craving and associated CP-AMPAR plasticity occur much more rapidly during withdrawal from methamphetamine compared with cocaine. However, a common mGluR1-based therapeutic strategy may be helpful for recovering cocaine and methamphetamine addicts. PMID- 27264311 TI - BMP7 gene polymorphisms are not associated with bone mineral density or osteoporotic fractures in postmenopausal Chinese women. AB - AIM: A previous study shows that bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with bone mineral density (BMD) in 920 European Americans. To determine the association of BMP7 polymorphisms and BMD and osteoporotic fracture susceptibility, we performed a case-control association study in postmenopausal Chinese women with or without osteoporotic fracture. METHODS: A total of 3815 unrelated postmenopausal Chinese women (1238 with osteoporotic fracture and 2577 healthy controls) were recruited. BMDs of the lumbar spine 1-4 (L1-4) and proximal femur (including total hip and femoral neck) were measured using dual-energy X-ray absorptiometry. Eight tagging single nucleotide polymorphisms (SNPs) in BMP7 gene, including rs11086598, rs4811822, rs12481628, rs6025447, rs230205, rs17404303, rs162316 and rs6127980, were genotyped. RESULTS: Among the 8 SNPs, rs6025447 and rs230205 were associated with total hip BMD (P=0.013 and 0.045, respectively). However, the associations became statistically insignificant after adjusting for age, height and weight. The TGTG haplotype of BMP7 gene was associated with total hip BMD (P=0.032), even after adjusting for age, height and weight (P=0.048); but the association was insignificant after performing the Bonferroni multiple-significance-test correction. Moreover, the 8 SNPs and 9 haplotypes of BMP7 gene were not associated with L1-4 or femoral neck BMD or osteoporotic fracture. CONCLUSION: This large-sample case-control association study suggests that the common genetic polymorphisms of BMP7 gene are not major contributors to variations in BMD or osteoporotic fracture in postmenopausal Chinese women. PMID- 27264312 TI - Novel CHOP activator LGH00168 induces necroptosis in A549 human lung cancer cells via ROS-mediated ER stress and NF-kappaB inhibition. AB - AIM: C/EBP homologous protein (CHOP) is a transcription factor that is activated at multiple levels during ER stress and plays an important role in ER stress induced apoptosis. In this study we identified a novel CHOP activator, and further investigated its potential to be a therapeutic agent for human lung cancer. METHODS: HEK293-CHOP-luc reporter cells were used in high-throughput screening (HTS) to identify CHOP activators. The cytotoxicity against cancer cells in vitro was measured with MTT assay. The anticancer effects were further examined in A549 human non-small cell lung cancer xenograft mice. The mechanisms underlying CHOP activation were analyzed using luciferase assays, and the anticancer mechanisms were elucidated in A549 cells. RESULTS: From chemical libraries of 50 000 compounds, LGH00168 was identified as a CHOP activator, which showed cytotoxic activities against a panel of 9 cancer cell lines with an average IC50 value of 3.26 MUmol/L. Moreover, administration of LGH00168 significantly suppressed tumor growth in A549 xenograft bearing mice. LGH00168 activated CHOP promoter via AARE1 and AP1 elements, increased DR5 expression, decreased Bcl-2 expression, and inhibited the NF-kappaB pathway. Treatment of A549 cells with LGH00168 (10 MUmol/L) did not induce apoptosis, but lead to RIP1 dependent necroptosis, accompanied by cell swelling, plasma membrane rupture, lysosomal membrane permeabilization, MMP collapse and caspase 8 inhibition. Furthermore, LGH00168 (10 and 20 MUmol/L) dose-dependently induced mito-ROS production in A549 cells, which was reversed by the ROS scavenger N-acetyl-L cysteine (NAC, 10 mmol/L). Moreover, NAC significantly diminished LGH00168 induced CHOP activation, NF-kappaB inhibition and necroptosis in A549 cells. CONCLUSION: LGH00168 is a CHOP activator that inhibits A549 cell growth in vitro and lung tumor growth in vivo. PMID- 27264313 TI - OL3, a novel low-absorbed TGR5 agonist with reduced side effects, lowered blood glucose via dual actions on TGR5 activation and DPP-4 inhibition. AB - AIM: TGR5 agonists stimulate intestinal glucagon-like peptide-1 (GLP-1) release, but systemic exposure causes unwanted side effects, such as gallbladder filling. In the present study, linagliptin, a DPP-4 inhibitor with a large molecular weight and polarity, and MN6, a previously described TGR5 agonist, were linked to produce OL3, a novel low-absorbed TGR5 agonist with reduced side-effects and dual function in lowering blood glucose by activation of TGR5 and inhibition of DPP-4. METHODS: TGR5 activation was assayed in HEK293 cells stably expressing human or mouse TGR5 and a CRE-driven luciferase gene. DPP-4 inhibition was assessed based on the rate of hydrolysis of a surrogate substrate. GLP-1 secretion was measured in human enteroendocrine NCI-H716 cells. OL3 permeability was tested in Caco-2 cells. Acute glucose-lowering effects of OL3 were evaluated in ICR and diabetic ob/ob mice. RESULTS: OL3 activated human and mouse TGR5 with an EC50 of 86.24 and 17.36 nmol/L, respectively, and stimulated GLP-1 secretion in human enteroendocrine NCI-H716 cells (3-30 MUmol/L). OL3 inhibited human and mouse DPP 4 with IC50 values of 18.44 and 69.98 MUmol/L, respectively. Low permeability of OL3 was observed in Caco-2 cells. In ICR mice treated orally with OL3 (150 mg/kg), the serum OL3 concentration was 101.10 ng/mL at 1 h, and decreased to 13.38 ng/mL at 5.5 h post dose, confirming the low absorption of OL3 in vivo. In ICR mice and ob/ob mice, oral administration of OL3 significantly lowered the blood glucose levels, which was a synergic effect of activating TGR5 that stimulated GLP-1 secretion in the intestine and inhibiting DPP-4 that cleaved GLP 1 in the plasma. In ICR mice, oral administration of OL3 did not cause gallbladder filling. CONCLUSION: OL3 is a low-absorbed TGR5 agonist that lowers blood glucose without inducing gallbladder filling. This study presents a new strategy in the development of potent TGR5 agonists in treating type 2 diabetes, which target to the intestine to avoid systemic side effects. PMID- 27264314 TI - A high-throughput-compatible assay to measure the degradation of endogenous Huntingtin proteins. AB - AIM: The accumulation of disease-causing proteins is a common hallmark of many neurodegenerative disorders. Measuring the degradation of such proteins using high-throughput-compatible assays is highly desired for the identification of genetic and chemical modulators of degradation. For example, Huntington's disease (HD) is an incurable hereditary neurodegenerative disorder caused by the cytotoxicity of mutant huntingtin protein (mHTT). The high-throughput measurement of mHTT degradation is important in HD drug discovery and research. Existing methods for such purposes have limitations due to their dependence on protein tags or pan protein synthesis inhibitors. Here, we report a high-throughput compatible pulse-chase method (CH-chase) for the measurement of endogenous tag free huntingtin protein (HTT) degradation based on Click chemistry and Homogeneous Time Resolved Fluorescence (HTRF) technologies. METHODS: The pulsed labeled proteins were conjugated with biotin using the click reaction strain promoted alkyne-azide cycloaddition (SPAAC), and the chase signals were calculated by measuring the reduction percentage of the HTT HTRF signals after pull-down with streptavidin beads. RESULTS: We validated that the signals were within the linear detection range and were HTT-specific. We successfully measured the degradation of endogenous HTT in a high-throughput-compatible format using 96 well plates. The predicted changes of HTT degradation by known modifiers were observed, which confirmed that the assay is suitable for the identification of HTT degradation modifiers. CONCLUSION: We have established the first high throughput-compatible assay capable of measuring endogenous, tag-free HTT degradation, providing a valuable tool for HD research and drug discovery. The method could be applied to other proteins and can facilitate research on other neurodegenerative disorders and proteinopathies. PMID- 27264315 TI - Activation of neuronal Kv7/KCNQ/M-channels by the opener QO58-lysine and its anti nociceptive effects on inflammatory pain in rodents. AB - AIM: The aim of this study was to examine the activation of neuronal Kv7/KCNQ channels by a novel modified Kv7 opener QO58-lysine and to test the anti nociceptive effects of QO58-lysine on inflammatory pain in rodent models. METHODS: Assays including whole-cell patch clamp recordings, HPLC, and in vivo pain behavioral evaluations were employed. RESULTS: QO58-lysine caused instant activation of Kv7.2/7.3 currents, and increasing the dose of QO58-lysine resulted in a dose-dependent activation of Kv7.2/Kv7.3 currents with an EC50 of 1.2+/-0.2 MUmol/L. QO58-lysine caused a leftward shift of the voltage-dependent activation of Kv7.2/Kv7.3 to a hyperpolarized potential at V1/2=-54.4+/-2.5 mV from V1/2= 26.0+/-0.6 mV. The half-life in plasma (t1/2) was derived as 2.9, 2.7, and 3.0 h for doses of 12.5, 25, and 50 mg/kg, respectively. The absolute bioavailabilities for the three doses (12.5, 25, and 50 mg/kg) of QO58-lysine (po) were determined as 13.7%, 24.3%, and 39.3%, respectively. QO58-lysine caused a concentration dependent reduction in the licking times during phase II pain induced by the injection of formalin into the mouse hindpaw. In the Complete Freund's adjuvant (CFA)-induced inflammatory pain model in rats, oral or intraperitoneal administration of QO58-lysine resulted in a dose-dependent increase in the paw withdrawal threshold, and the anti-nociceptive effect on mechanical allodynia could be reversed by the channel-specific blocker XE991 (3 mg/kg). CONCLUSION: Taken together, our findings show that a modified QO58 compound (QO58-lysine) can specifically activate Kv7.2/7.3/M-channels. Oral or intraperitoneal administration of QO58-lysine, which has improved bioavailability and a half-life of approximately 3 h in plasma, can reverse inflammatory pain in rodent animal models. PMID- 27264316 TI - Re: 'Lost in Translation: Time to Re-evaluate Our Definitions'. PMID- 27264317 TI - Lost in Translation: Time to Re-evaluate Our Definitions. PMID- 27264318 TI - Bacterial communities in Arctic first-year drift ice during the winter/spring transition. AB - Horizontal and vertical variability of first-year drift-ice bacterial communities was investigated along a North-South transect in the Fram Strait during the winter/spring transition. Two different developmental stages were captured along the transect based on the prevailing environmental conditions and the differences in bacterial community composition. The differences in the bacterial communities were likely driven by the changes in sea-ice algal biomass (2.6-5.6 fold differences in chl-a concentrations). Copiotrophic genera common in late spring/summer sea ice, such as Polaribacter, Octadecabacter and Glaciecola, dominated the bacterial communities, supporting the conclusion that the increase in the sea-ice algal biomass was possibly reflected in the sea-ice bacterial communities. Of the dominating bacterial genera, Polaribacter seemed to benefit the most from the increase in algal biomass, since they covered approximately 39% of the total community at the southernmost stations with higher (>6 MUg l(-1) ) chl-a concentrations and only 9% at the northernmost station with lower chl-a concentrations (<6 MUg l(-1) ). The sea-ice bacterial communities also varied between the ice horizons at all three stations and thus we recommend that for future studies multiple ice horizons be sampled to cover the variability in sea ice bacterial communities in spring. PMID- 27264320 TI - [Qulity is always the lifeline of pathologic diagnosis]. PMID- 27264321 TI - [Status and application of molecular pathoogy in development of personalized medicine in cancer therapy]. PMID- 27264322 TI - [Issues and challenges in diagnosis of soft tissue tumors]. PMID- 27264319 TI - Evaluation of a physiotherapy-led group rehabilitation intervention for adults living with HIV: referrals, adherence and outcomes. AB - HIV is characterised by episodes of disability. We report a novel, hospital outpatient rehabilitation intervention, combining physiotherapy-led group exercise and education for people living with HIV (PLWH). This observational study evaluated routine delivery of the 10-week intervention in terms of referral patterns, rehabilitation goals, intervention adherence and change in patient outcomes. Measurements at baseline & 10 weeks included locomotor performance (6 minute walk test; 6MWT), flexibility, upper and lower limb strength and health related quality of life (HRQOL). Adherence was defined as attending >=8/20 sessions, with reasons for non-adherence identified in retrospective telephone interviews. Goal Attainment Scale measured progression to individual goals. Total 92 referrals were mostly for musculoskeletal (25.0%), oncological (19.6%) or cardio-metabolic (18.5%) reasons, and mostly male (81.5%), Caucasian (70.7%) and older (mean 51.5 years). Common themed rehabilitation goals included improving body image, participation, mobility, health/fitness and function. Adherence was achieved by 42 (46%) patients, with open access utilised by 34 patients, returning (n = 19) or restarting when non-adherent (n = 15). Post-intervention measurements collected for 37 (40%) patients demonstrated improvements in 6MWT distance (p < .001), flexibility (p < .001), strength in triceps (p < .001), biceps (p < .001), Lattisimus Dorsi (p < .001), shoulder-press (p < .001), chest press (p < 0.001), and leg-press (p < 0.001). HRQOL improved in total score (p < .001), physical (p < .001), emotional (p < .001) and functional (p = .065) subscales. Extent of goal achievement demonstrated 83% of goals was "expected" (n = 57), "somewhat more" (n = 31) or "much more" (n = 14). Reasons for non adherence from 21 telephone interviews identified physical health challenges, individual factors and time or location issues. This novel rehabilitation approach for PLWH improved function, HRQOL and goal attainment among those completing the intervention. Sub-optimal adherence likely relates to episodic disability. PMID- 27264323 TI - [Pathologic changes of lesions made in vivo by multi-pole radiofrequency ablation system in long bones of swine limbs]. PMID- 27264324 TI - [Effects of glucose-6-phosphate dehydrogenase expression down-regulation on cell apoptosis and invasion ability in cutaneous squamous cell carcinoma A431 cells]. PMID- 27264325 TI - [Application of fluorescence in-situ hybridization in tissue microarray]. PMID- 27264326 TI - [Multiple glomangiomatosis: report of a case]. PMID- 27264327 TI - [Cryptococcosis of forearm bone and periosteal soft tissue: report of a case]. PMID- 27264328 TI - [Type II enteropathy-associated T-cell lymphoma presenting with whole gastrointestinal tract involvement: report of a case]. PMID- 27264329 TI - [Sebaceous lymphadenoma of parotid gland: report of a case]. PMID- 27264330 TI - [Post-transplant lymphoproliferative disorder involving central nervous system: report of a case]. PMID- 27264331 TI - [Mesenchymal-epithelial transition in soft tissue sarcoma: an overview and update]. PMID- 27264332 TI - [Clinicopathologic features of gastroblastoma]. PMID- 27264333 TI - The burden of road traffic injuries in Kermanshah Province, Iran, in 2010-2011: GBD 2010 method. AB - Deaths, injuries and disabilities resulting from road traffic injuries (RTIs) are a public health major concern. This study aims to calculate the burden of RTIs in Kermanshah Province in Iran. In this study to determine the years of life lost (YLL) related to RTIs, the National Death Registration and Forensics Medicine census data were employed. We use forensic medicine data to calculate the incidence of non-fatal injuries and years lost due to disability (YLD). The cause of death and non-fatal injuries was classified using ICD-10 codes and 23 groupes of global burden of diseases (GBD) 2010. The disability-adjusted life year (DALY) estimated on the guidelines of the GBD 2010 and age and sex structure was taken from the National Statistic Center for the year 2010. Overall, 70.8% of the subjects were males. The fatal and non-fatal injury rates of RTI were 51.3 and 283.6 per 100,000 persons, respectively. YLLs and YLDs were 46613 (24.5 per 1000) and 3405 (1.8 per 1000) in both sexes, respectively. The disability adjusted life years were 40711 in males, 9306 in females and 50018 in both sexes (42.5, 9.8 and 26.3 per 1000, respectively). More than 93% of DALY was from YLL (24.5 per 1000), with a small proportion for YLD (1.8 per 1000). Accounting for more than 50,000 DALY attributed to RTIs, traffic injuries is a major public health and socioeconomic problem in Kermanshah. Designing cost-effective interventions based on comprehensive and multi-sectoral programmes at the national and provincial levels can save many lives and resources that are lost every year. Undoubtedly, establishing a surveillance system at the sub-national level and measuring the burden of injuries, as in this study, can help policy-makers and planners in lessening the burden of RTIs. PMID- 27264334 TI - Innate immune memory in mammals. AB - Innate and adaptive immunity have evolved as sophisticated mechanisms of host defence against invading pathogens. Classically the properties attributed to innate immunity are its rapid pleiotropic response, and to adaptive immunity its specificity and ability to retain a long-term memory of past infections. It is now clear that innate immunity also contributes to raising a memory response upon pathogenic assault. In this review we will discuss the interaction between bacterial, viral, fungal and parasitic molecular patterns and innate immune cells in which a memory response is imposed, or has the potential to be imposed. PMID- 27264335 TI - Innate immune memory in plants. AB - The plant innate immune system comprises local and systemic immune responses. Systemic plant immunity develops after foliar infection by microbial pathogens, upon root colonization by certain microbes, or in response to physical injury. The systemic plant immune response to localized foliar infection is associated with elevated levels of pattern-recognition receptors, accumulation of dormant signaling enzymes, and alterations in chromatin state. Together, these systemic responses provide a memory to the initial infection by priming the remote leaves for enhanced defense and immunity to reinfection. The plant innate immune system thus builds immunological memory by utilizing mechanisms and components that are similar to those employed in the trained innate immune response of jawed vertebrates. Therefore, there seems to be conservation, or convergence, in the evolution of innate immune memory in plants and vertebrates. PMID- 27264336 TI - Western-style diet, sex steroids and metabolism. AB - The evolutionary transition from hunting to farming was associated with introduction of carbohydrate-rich diets. Today, the increased consumption of simple sugars and high-fat food brought about by Western-style diet and physical inactivity are leading causes of the growing obesity epidemic in the Western society. The extension of human lifespan far beyond reproductive age increased the burden of metabolic disorders associated with overnutrition and age-related hypogonadism. Sex steroids are essential regulators of both reproductive function and energy metabolism, whereas their imbalance causes infertility, obesity, glucose intolerance, dyslipidemia, and increased appetite. Clinical and translational studies suggest that dietary restriction and weight control can improve metabolic and reproductive outcomes of sex hormone-related pathologies, including testosterone deficiency in men and natural menopause and hyperandrogenemia in women. Minimizing metabolic and reproductive decline through rationally designed diet and exercise can help extend human reproductive age and promote healthy aging. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy. PMID- 27264338 TI - The interactions of mothers with eating disorders with their toddlers: identifying broader risk factors. AB - The connection between maternal eating disorders and feeding and eating problems among their children has been substantially demonstrated. This pilot study focused on the interactions between mothers with eating disorders and their toddlers in non-feeding situations. Twenty-eight dyads of mothers with prenatal eating disorders and their toddlers were compared to a case-matched control group with no eating disorder. Maternal current eating and co-occurring psychopathology, children's symptoms and mother-child interactions were measured. Mothers with eating disorders were less sensitive to their children, tried to control their children's behaviors more, and were less happy during mother-child interactions. The children in the maternal eating disorder group were rated as less responsive to their mothers and their mothers also reported more behavioral problems than those in the control group. Findings imply that maternal eating disorders may be linked with a wide range of adverse maternal and child behaviors beyond those associated with eating. PMID- 27264337 TI - Are circulating microRNAs peripheral biomarkers for Alzheimer's disease? AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, multiple cognitive abnormalities and intellectual impairments. Currently, there are no drugs or agents that can delay and/or prevent the progression of disease in elderly individuals, and there are no peripheral biomarkers that can detect AD early in its pathogenesis. Research has focused on identifying biomarkers for AD so that treatment can be begun as soon as possible in order to restrict or prevent intellectual impairments, memory loss, and other cognitive abnormalities that are associated with the disease. One such potential biomarker is microRNAs that are found in circulatory biofluids, such as blood and blood components, serum and plasma. Blood and blood components are primary sources where miRNAs are released in either cell-free form and then bind to protein components, or are in an encapsulated form with microvesicle particles. Exosomal miRNAs are known to be stable in biofluids and can be detected by high throughput techniques, like microarray and RNA sequencing. In AD brain, enriched miRNAs encapsulated with exosomes crosses the blood brain barrier and secreted in the CSF and blood circulations. This review summarizes recent studies that have identified miRNAs in the blood, serum, plasma, exosomes, cerebral spinal fluids, and extracellular fluids as potential biomarkers of AD. Recent research has revealed only six miRNAs - miR-9, miR-125b, miR-146a, miR-181c, let-7g-5p, and miR-191-5p - that were reported by multiple investigators. Some studies analyzed the diagnostic potential of these six miRNAs through receiver operating curve analysis which indicates the significant area-under-curve values in different biofluid samples. miR-191-5p was found to have the maximum area-under-curve value (0.95) only in plasma and serum samples while smaller area-under-curve values were found for miR-125, miR-181c, miR-191-5p, miR-146a, and miR-9. This article shortlisted the promising miRNA candidates and discussed their diagnostic properties and cellular functions in order to search for potential biomarker for AD. PMID- 27264339 TI - Arabidopsis YAK1 regulates abscisic acid response and drought resistance. AB - Abscisic acid (ABA) is an important phytohormone that controls several plant processes such as seed germination, seedling growth, and abiotic stress response. Here, we report that AtYak1 plays an important role in ABA signaling and postgermination growth in Arabidopsis. AtYak1 knockout mutant plants were hyposensitive to ABA inhibition of seed germination, cotyledon greening, seedling growth, and stomatal movement. atyak1-1 mutant plants display reduced drought stress resistance, as evidenced by water loss rate and survival rate. Molecular genetic analysis revealed that AtYak1 deficiency led to elevated expression of stomatal-related gene, MYB60, and down-regulation of several stress-responsive genes. Altogether, these results indicate that AtYak1 plays a role as a positive regulator in ABA-mediated drought response in Arabidopsis. PMID- 27264340 TI - Optical coherence tomography of basal cell carcinoma: density and signal attenuation. AB - BACKGROUND: Basal cell carcinoma (BCC) is the most prevalent malignancy in Caucasians. Optical coherence tomography (OCT) is a non-invasive optical imaging technology using the principle of interferometry. OCT has shown a great potential in diagnosing, monitoring, and follow-up of BCC. So far most OCT studies on the subject of BCC have had a qualitative focus, i.e. on morphological analysis of the OCT images. The aim of this study was to explore the use of quantitative OCT measurements, density, and attenuation coefficient in BCC lesions as a way to improve the OCT evaluation of BCC. METHODS: The study was based on OCT images of 58 histologically verified BCC lesions and the corresponding normal adjacent skin. The study population was divided into two groups based on the OCT morphology of the BCC lesions: the "Disrupt BCC group" and the "Nodular BCC group". Density and attenuation coefficients were measured in the OCT images by specially designed software and the regions of interests (ROI) were placed directly on (ROI1) and under the visible BCC lesions (ROI2). The results were compared to the OCT images of normal adjacent skin. RESULTS: Disrupt BCC group: The densities of BCC lesions were significant lower (P = 0.002), than the normal skin in ROI1. Attenuation measurements were found to be significantly greater (P = 0.012) in BCC lesions compared to normal skin in ROI1. Nodular BCC group: Attenuation measurements were found to be significantly lower (P = 0.017) in BCC lesions compared to normal skin in ROI1. CONCLUSIONS: Our study suggests a quantitative potential of OCT in the context of BCC. This study is exploratory and requires independent verification. PMID- 27264342 TI - Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome? AB - BACKGROUND: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico striatal connectivity, especially between left putamen and frontal associative areas. METHODS: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). RESULTS: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. DISCUSSION: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub. PMID- 27264341 TI - Imaging cellular structures in super-resolution with SIM, STED and Localisation Microscopy: A practical comparison. AB - Many biological questions require fluorescence microscopy with a resolution beyond the diffraction limit of light. Super-resolution methods such as Structured Illumination Microscopy (SIM), STimulated Emission Depletion (STED) microscopy and Single Molecule Localisation Microscopy (SMLM) enable an increase in image resolution beyond the classical diffraction-limit. Here, we compare the individual strengths and weaknesses of each technique by imaging a variety of different subcellular structures in fixed cells. We chose examples ranging from well separated vesicles to densely packed three dimensional filaments. We used quantitative and correlative analyses to assess the performance of SIM, STED and SMLM with the aim of establishing a rough guideline regarding the suitability for typical applications and to highlight pitfalls associated with the different techniques. PMID- 27264343 TI - Functional neuroimaging and clinical features of drug naive patients with de novo Parkinson's disease and probable RBD. AB - INTRODUCTION: The association between Parkinson Disease (PD) and REM sleep behavior disorder (RBD) has been related to a specific, malignant clinical phenotype. Definite RBD diagnosis requires video-polysomnography that is often unfeasible. A malignant clinical PD-RBD phenotype could be expected also in PD patients with probable RBD. Aim of this cross-sectional study was to evaluate whether a more severe neuropsychological and functional neuroimaging phenotype can be identified in PD patients with probable RBD. METHODS: Thirty-eight de novo, drug naive PD patients underwent a first-line clinical assessment and a second-line multimodal assessment, including neuropsychological evaluation, (123)I-FP-CIT-SPECT and (18)F-FDG-PET, which were compared between PD patients with (PD + RBD+) and without (PD + RBD-) probable RBD. RESULTS: On first-line assessment, PD + RBD + patients had significantly more constipation (p = 0.02) and showed worse olfaction (p = 0.01) compared with PD + RBD-while the two groups were similar as for age, presence of orthostatic hypotension, UPDRS-III and MMSE scores. On second-line assessment, PD + RBD + patients showed a worse neuropsychological test profile, more severe nigro-striatal dopaminergic impairment, mainly at caudate level in the less affected hemisphere (p = 0.004) and impaired brain glucose metabolism, with relative hypometabolism in posterior cortical regions and relative hypermetabolism mainly in anterior regions of the more affected hemisphere (p = 0.015). CONCLUSIONS: PD patients with probable RBD are likely to have a more severe neuropsychological and functional brain-imaging phenotype already at the time of diagnosis. PMID- 27264346 TI - Tropical Medicine & International Health. PMID- 27264344 TI - The prevalence of dementia with Lewy bodies in a rural area of China. AB - INTRODUCTION: Data on the prevalence of dementia with Lewy bodies (DLB) in China are limited. The aim of this study was to estimate the prevalence of DLB in individuals aged 60 years and older and to analyze the associated risk factors and clinical features of DLB. METHODS: We conducted a cross-sectional, two-phase, door-to-door, population-based study that included 5542 participants aged at least 60 years who resided in Ji County. In phase I of the study, we used the Mini-Mental State Examination, the Clinical Dementia Rating scale, and the Activities of Daily Living scale to screen for dementia. Any person who was suspected of having dementia underwent a clinical examination, blood tests, and a neuroimaging examination to confirm the diagnosis of dementia. In phase II of the study, we further screened eligible participants for DLB using consensus guidelines for the clinical and pathologic diagnosis of DLB. RESULTS: The overall prevalence of DLB in the total population of 5542 study participants was 1.05%; the prevalence of DLB was 10.10% in the population with dementia. Compared to individuals without cognitive impairment, patients with DLB were less engaged in social activities. Having fewer than 5 years of formal education might be a risk factor for DLB. The three core symptoms of DLB - fluctuating cognition, visual hallucinations, and Parkinsonism - were observed in 60.34%, 68.97%, and 63.79% of patients with DLB, respectively. CONCLUSION: Our study provides the first information of the prevalence of DLB in a rural area of China. PMID- 27264347 TI - Exceptional high fatigue strength in Cu-15at.%Al alloy with moderate grain size. AB - It is commonly proposed that the fatigue strength can be enhanced by increasing the tensile strength, but this conclusion needs to be reconsidered according to our study. Here a recrystallized alpha-Cu-15at.%Al alloy with moderate grain size of 0.62 MUm was fabricated by cold rolling and annealing, and this alloy achieved exceptional high fatigue strength of 280 MPa at 10(7) cycles. This value is much higher than the fatigue strength of 200 MPa for the nano-crystalline counterpart (0.04 MUm in grain size) despite its higher tensile strength. The remarkable improvement of fatigue strength should be mainly attributed to the microstructure optimization, which helps achieve the reduction of initial damage and the dispersion of accumulated damage. A new strategy of "damage reduction" was then proposed for fatigue strength improvement, to supplement the former strengthening principle. The methods and strategies summarized in this work offer a general pathway for further improvement of fatigue strength, in order to ensure the long term safety of structural materials. PMID- 27264348 TI - Diagnostic value of angled oblique sagittal images of the supraspinatus tendon for the detection of rotator cuff tears on MR imaging. AB - PURPOSE: The goal of this study was to evaluate the added value of sagittal T2 weighted magnetic resonance imaging (MRI) of the supraspinatus tendon by comparison with a standard MRI protocol for the evaluation of the rotator cuff. MATERIALS AND METHODS: This retrospective single center study included 100 patients referred for MRI for suspected rotator cuff injuries. Two observers compared sagittal T2-weighted fat-suppressed orthogonal images of the distal portion of the supraspinatus muscle ("cuff" protocol) to those acquired according to the standard MRI protocol, which focuses on the glenoid. The two observers evaluated the appearance of each rotator cuff tendon and indicated whether the "cuff protocol" facilitated interpretation. RESULTS: The sensitivity and specificity for the detection of lesions ranged from 79 to 97% and 80 to 99% respectively. The interobserver variability coefficient was good for the supraspinatus (k=0.744). The new sequence helped localize and characterize rotator cuff injuries in 24-40% of the cases for the supraspinatus, in particular for partial tears and tendinopathies. CONCLUSION: The results of the specific MRI "cuff" protocol focusing on the supraspinatus are good, and helps facilitate interpretation of MRIs of the rotator cuff by non-specialist radiologists, in particular of the supraspinatus muscle. PMID- 27264345 TI - Copy-number variation of MCL1 predicts overall survival of non-small-cell lung cancer in a Southern Chinese population. AB - BCL2L1 and MCL1 are key anti-apoptotic genes, and critical for cancer progression. The prognostic values of BCL2L1 and MCL1 copy-number variations (CNVs) in non-small-cell lung cancer (NSCLC) remain largely unknown. Somatic CNVs in BCL2L1 and MCL1 genes were tested in tumor tissues from 516 NSCLC patients in southern China; afterward, survival analyses were conducted with overall survival (OS) as outcome. Additionally, the associations between CNVs and mRNA expression levels were explored using data from 986 NSCLC patients in the Cancer Genome Atlas project. It was found that amplifications of BCL2L1 and MCL1 were associated with unfavorable OS of NSCLC, with adjusted hazards ratio of 1.62 (95% confident interval [CI] = 1.10-2.40; P = 0.015) and 1.39 (95% CI = 1.05-1.84; P = 0.020), respectively. Amplifications of MCL1, but not BCL2L1, were related with higher mRNA expression levels of corresponding gene, compared with non amplifications (P = 0.005). Interestingly, after incorporating with MCL1 CNV status, clinical variables (age, sex, TNM stage, and surgical approach) showed an improved discriminatory ability to classify OS (area under curve increased from 72.2% to 74.1%; P = 0.042, DeLong's test). Overall, MCL1 CNV might be a prognostic biomarker for NSCLC, and additional investigations are needed to validate our findings. PMID- 27264349 TI - Nutcracker syndrome: The role of three-dimensional imaging for the diagnosis. PMID- 27264350 TI - Editorial Comment. PMID- 27264351 TI - Editorial Comment. PMID- 27264352 TI - Editorial Comment. PMID- 27264353 TI - Reply by Authors. PMID- 27264354 TI - Comparing results from multiple imputation and dynamic marginal structural models for estimating when to start antiretroviral therapy. AB - Optimal timing of initiating antiretroviral therapy has been a controversial topic in HIV research. Two highly publicized studies applied different analytical approaches, a dynamic marginal structural model and a multiple imputation method, to different observational databases and came up with different conclusions. Discrepancies between the two studies' results could be due to differences between patient populations, fundamental differences between statistical methods, or differences between implementation details. For example, the two studies adjusted for different covariates, compared different thresholds, and had different criteria for qualifying measurements. If both analytical approaches were applied to the same cohort holding technical details constant, would their results be similar? In this study, we applied both statistical approaches using observational data from 12,708 HIV-infected persons throughout the USA. We held technical details constant between the two methods and then repeated analyses varying technical details to understand what impact they had on findings. We also present results applying both approaches to simulated data. Results were similar, although not identical, when technical details were held constant between the two statistical methods. Confidence intervals for the dynamic marginal structural model tended to be wider than those from the imputation approach, although this may have been due in part to additional external data used in the imputation analysis. We also consider differences in the estimands, required data, and assumptions of the two statistical methods. Our study provides insights into assessing optimal dynamic treatment regimes in the context of starting antiretroviral therapy and in more general settings. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27264355 TI - Distinct Defects in Synaptic Differentiation of Neocortical Neurons in Response to Prenatal Valproate Exposure. AB - Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by impairments in social interactions and stereotyped behaviors. Valproic acid (VPA) is frequently used to treat epilepsy and bipolar disorders. When taken during pregnancy, VPA increases the risk of the unborn child to develop an ASD. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Therefore, such rodent models may allow for identification of synaptic pathophysiology underlying ASD risk. Here, we systematically probed alterations in synaptic proteins that might contribute to autism-related behavior in the offspring of in utero VPA-exposed mice. Moreover, we tested whether direct VPA exposure of cultured neocortical neurons may recapitulate the molecular alterations seen in vivo. VPA-exposed neurons in culture exhibit a significant increase in the number of glutamatergic synapses accompanied by a significant decrease in the number of GABAergic synapses. This shift in excitatory/inhibitory balance results in substantially increased spontaneous activity in neuronal networks arising from VPA-exposed neurons. Pharmacological experiments demonstrate that the alterations in GABAergic and glutamatergic synaptic proteins and structures are largely caused by inhibition of histone deacetylases. Therefore, our study highlights an epigenetic mechanism underlying the synaptic pathophysiology in this ASD model. PMID- 27264356 TI - Resistance Elasticity of Antibiotic Demand in Intensive Care. AB - The emergence and spread of antimicrobial resistance (AMR) is still an unresolved problem worldwide. In intensive care units (ICUs), first-line antibiotic therapy is highly standardized and widely empiric while treatment failure because of AMR often has severe consequences. Simultaneously, there is a limited number of reserve antibiotics, whose prices and/or side effects are substantially higher than first-line therapy. This paper explores the implications of resistance induced substitution effects in ICUs. The extent of such substitution effects is shown in a dynamic fixed effect regression analysis using a panel of 66 German ICUs with monthly antibiotic use and resistance data between 2001 and 2012. Our findings support the hypothesis that demand for reserve antibiotics substantially increases when resistance towards first-line agents rises. For some analyses the lagged effect of resistance is also significant, supporting the conjecture that part of the substitution effect is caused by physicians changing antibiotic choices in empiric treatment by adapting their resistance expectation to new information on resistance prevalence. The available information about resistance rates allows physicians to efficiently balance the trade-off between exacerbating resistance and ensuring treatment success. However, resistance-induced substitution effects are not free of charge. These effects should be considered an indirect burden of AMR. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27264358 TI - Regeneration and rewiring of rodent olfactory sensory neurons. AB - The olfactory sensory neurons are the only neurons in the mammalian nervous system that not only regenerate naturally and in response to injury, but also project to specific targets in the brain. The stem cells in the olfactory epithelium commit to both neuronal and non-neuronal lineages depending on the environmental conditions. They provide a continuous supply of new neurons. A newly generated neuron must express a specific odorant receptor gene and project to a central target consist of axons expressing the same receptor type. Recent studies have provided insights into this highly regulated, complex process. However, the molecular mechanisms that determine the regenerative capacity of stem cells, and the ability of newly generated neurons in directing their axons toward specific targets, remain elusive. Here we review progresses and controversies in the field and offer testable models. PMID- 27264357 TI - NT-3 promotes proprioceptive axon regeneration when combined with activation of the mTor intrinsic growth pathway but not with reduction of myelin extrinsic inhibitors. AB - Although previous studies have identified several strategies to stimulate regeneration of CNS axons, extensive regeneration and functional recovery have remained a major challenge, particularly for large diameter myelinated axons. Within the CNS, myelin is thought to inhibit axon regeneration, while modulating activity of the mTOR pathway promotes regeneration of injured axons. In this study, we examined NT-3 mediated regeneration of sensory axons through the dorsal root entry zone in a triple knockout of myelin inhibitory proteins or after activation of mTOR using a constitutively active (ca) Rheb in DRG neurons to determine the influence of environmental inhibitory or activation of intrinsic growth pathways could enhance NT-3-mediate regeneration. Loss of myelin inhibitory proteins showed modest enhancement of sensory axon regeneration. In mTOR studies, we found a dramatic age related decrease in the mTOR activation as determined by phosphorylation of the downstream marker S6 ribosomal subunit. Expression of caRheb within adult DRG neurons in vitro increased S6 phosphorylation and doubled the overall length of neurite outgrowth, which was reversed in the presence of rapamycin. In adult female rats, combined expression of caRheb in DRG neurons and NT-3 within the spinal cord increased regeneration of sensory axons almost 3 fold when compared to NT-3 alone. Proprioceptive assessment using a grid runway indicates functionally significant regeneration of large-diameter myelinated sensory afferents. Our results indicate that caRheb induced increase in mTOR activation enhances neurotrophin-3 induced regeneration of large-diameter myelinated axons. PMID- 27264360 TI - Visualization of Diffusion within Nanoarrays. AB - The direct experimental characterization of diffusion processes at nanoscale remains a challenge that could help elucidate processes in biology, medicine and technology. In this report, two experimental approaches were employed to visualize ion diffusion profiles at the orifices of nanopores (radius (ra) of 86 +/- 6 nm) in array format: (1) electrochemically assisted formation of silica deposits based on surfactant ion transfer across nanointerfaces between two immiscible electrolyte solutions (nanoITIES); (2) combined atomic force - scanning electrochemical microscopy (AFM-SECM) imaging of topography and redox species diffusion through the nanopores. The nature of the diffusion zones formed around the pores is directly related to the interpore distance within the array. Nanopore arrays with different ratios of pore center-to-center separation (rc) to pore radius (ra) were fabricated by focused ion beam (FIB) milling of silicon nitride (SiN) membranes, with 100 pores in a hexagonal arrangement. The ion diffusion profiles determined by the two visualization methods indicated the formation of overlapped or independent diffusion profiles at nanopore arrays with rc/ra ratios of 21 +/- 2 and 91 +/- 7, respectively. In particular, the silica deposition method resulted in formation of a single deposit encompassing the complete array with closer nanopore arrangement, whereas individual silica deposits were formed around each nanopore within the more widely spaced array. The methods reveal direct experimental evidence of diffusion zones at nanopore arrays and provide practical illustration that the pore-pore separation within such arrays has a significant impact on diffusional transport as the pore size is reduced to the nanoscale. These approaches to nanoscale diffusion zone visualization open up possibilities for better understanding of molecular transport processes within miniaturized systems. PMID- 27264361 TI - Inflammatory bowel disease treatment. PMID- 27264359 TI - Cutaneous tissue damage induces long-lasting nociceptive sensitization and regulation of cellular stress- and nerve injury-associated genes in sensory neurons. AB - Tissue damage is one of the major etiological factors in the emergence of chronic/persistent pain, although mechanisms remain enigmatic. Using incision of the back skin of adult rats as a model for tissue damage, we observed sensitization in a nociceptive reflex enduring to 28days post-incision (DPI). To determine if the enduring behavioral changes corresponded with a long-term impact of tissue damage on sensory neurons, we examined the temporal expression profile of injury-regulated genes and the electrophysiological properties of traced dorsal root ganglion (DRG) sensory neurons. The mRNA for the injury/stress-hub gene Activating Transcription Factor 3 (ATF3) was upregulated and peaked within 4 DPI, after which levels declined but remained significantly elevated out to 28 DPI, a time when the initial incision appears healed and tissue-inflammation largely resolved. Accordingly, stereological image analysis indicated that some neurons expressed ATF3 only transiently (mostly medium-large neurons), while in others it was sustained (mostly small neurons), suggesting cell-type-specific responses. In retrogradely-traced ATF3-expressing neurons, Calcium/calmodulin dependent protein kinase type IV (CAMK4) protein levels and isolectin-B4 (IB4) binding were suppressed whereas Growth Associated Protein-43 (GAP-43) and Neuropeptide Y (NPY) protein levels were enhanced. Electrophysiological recordings from DiI-traced sensory neurons 28 DPI showed a significant sensitization limited to ATF3-expressing neurons. Thus, ATF3 expression is revealed as a strong predictor of single cells displaying enduring pain-related electrophysiological properties. The cellular injury/stress response induced in sensory neurons by tissue damage and indicated by ATF3 expression is positioned to contribute to pain which can occur after tissue damage. PMID- 27264362 TI - Allogeneic leukocytes in cardiac surgery: Good or bad? AB - Worldwide, cardiac surgery is a common procedure requiring a large quantity of allogeneic blood products, which are associated with postoperative complications. Leukocytes present in blood products may play a role in these complications, which are referred to as transfusion-related immunomodulation (TRIM). Several randomized controlled trials (RCTs) in different settings investigated the effects of allogeneic leukocytes in red blood cells (RBCs). Cardiac surgery studies reported a reduction in postoperative infections and mortality in patients that received leukocyte-reduced RBCs compared with leukocyte-containing RBCs; this was mainly due to more deaths due to infections and multiple organ dysfunction syndrome (MODS) in the group that received leukocyte-containing RBCs. Patients with postoperative complications had higher concentrations of inflammatory mediators. These findings suggest that leukocyte-containing transfusion during cardiac surgery induces a second insult to the systemic inflammatory response. In the present review we discuss the possible role of blood transfusions in cardiac surgery. Especially, we focus on the possible role of allogeneic leukocytes associated with postoperative complications after cardiac surgery. PMID- 27264363 TI - The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura. AB - OBJECTIVE: To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP) some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-alpha) -308 G/A and transforming growth factor-beta 1 (TGF-beta1) -915 G/C polymorphisms in the development and clinical progression of childhood ITP. METHODS: In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP) and 48 healthy controls were investigated via LightCycler(r) PCR analysis for TNF-alpha -308 G/A and TGF-beta1 -915 G/C polymorphisms. RESULTS: The frequency of TNF-alpha -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The frequency of TGF-beta1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The risk of developing ITP and clinical progression were not associated with TNF-alpha -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249) or TGF-beta1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755) polymorphisms. CONCLUSION: The frequency of TNF-alpha -308 G/A and TGF-beta1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease. PMID- 27264364 TI - Influence of detection of pretreatment cytogenetic abnormalities on first complete remission and survival in adult acute lymphoblastic leukemia. AB - OBJECTIVE: Treatment of acute lymphoblastic leukemia (ALL) in adults focuses on the initial assessment of the prognostic relevant cytogenetic features as well as a response-guided therapy based on molecular data. We examined the importance of molecular-cytogenetic abnormalities for complete remission (CR) rates and the overall survival (OS) in adult ALLs. METHODS: Conventional cytogenetics and fluorescence in situ hybridization were performed on bone marrow cells from 33 newly-diagnosed ALL adults. Two karyotype categories [standard- risk group- normal karyotype, hyperdiplody and other structural aberrations, and high-risk group-t(11q23)/MLL, t(9;22)/bcr-abl, t(1;19), t(8;14), C-MYC and complex karyotype] and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. RESULTS: Chromosomal abnormalities were found in 52% of the cases with a high rate of poor-risk translocations - t(9;22), t(8q24), t(11q23), t(1;19). The total CR rate was 67% and the median time for achievement 2.33 months. Male sex, an age below 35 years and the absence of high risk translocations might have contributed to the high CR rates. Female patients, hyperdiplody, low white blood cells (WBC), and random cytogenetic aberrations had the longest OS. OS, 3- and 5-years survival periods were significantly shorter for poor-risk than standard risk group (p=.015, p=.001 and p=.005, respectively). CONCLUSION: This study emphasizes the lack of influence of cytogenetic aberrations on the CR and the time to achieve CR. However, our observations show that these aberrations are an independent prognostic factor in adult ALL - they allow predicting therapy resistance and the OS time after intense treatment. PMID- 27264365 TI - Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients. AB - OBJECTIVE: The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations. METHODS: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. RESULTS: Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22)(q11;q13;q34;q11). CONCLUSION: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3)(q24;q34;q11;q21) apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22)(q11;q13;q34;q11) full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients. PMID- 27264366 TI - Outcomes in 102 patients that present to the emergency department with chemotherapy-induced febrile neutropenia. AB - OBJECTIVE: Febrile neutropenia (FN) is a major toxic responseto chemotherapy requiring prompt medical attention. There are a limited number of reports on clinical outcome in patients with FN that present to emergency departments. METHODS: We retrospectively evaluated clinical manifestations, therapeutic outcomes, and risk factors for FN in 102 adult patients that presented to the emergency department between 1 January 2006 and 31 March 2009. FN was defined as a body temperature>38 degrees C and a neutrophil count >0.5*109/L on the day of fever onset or the day after. RESULTS: Mean age of the patients was 57 years. Mean absolute neutrophil count (ANC) was 436.8/mm3 (range: 0-1000/mm3). In all, 23 of the patients (22.5%) died due to complications related to FN. There were not a statistical difference in therapeutic outcome among tumor types, performance status, sex, depth of neutropenia, or time from emergency department presentationto initiation of antibiotic therapy. Age was an important prognostic factor for therapeutic outcome. Mean age of fatal cases was 65 years versus 56 years for non-fatal cases (p=0.016). Bacteremia was noted in 19 patients, 10 (53%) of which died. The mortality rate was significantly higher in thepatients with blood culture-proven bacteria than in those whose blood culture yielded no organism (p=0.013). CONCLUSION: FN patients that presented to the emergency department had a high mortality rate that increased with age. Given the increasing age of patients diagnosed with cancer as well as therapeutic interventions, the high mortality rate associated withchemotherapy-induced FN in elderly patients requires further study in order to reduce the risk of death. PMID- 27264367 TI - Management of autoimmune hemolytic anemia in children and adolescents: A single center experience. AB - OBJECTIVE: To present and discuss the treatment of autoimmune hemolytic anemia (AIHA). METHODS: The medical records of all patients (n=19) diagnosed in a tertiary hematology center between 1999 and 2010 were retrospectively reviewed. RESULTS: Median age at diagnosis of AIHA was 5 years (range: 4 months-17 years). In all, 13 patients had primary (idiopathic) AIHA, whereas 2 had primary Evans Syndrome (ES), 2 had autoimmune lymphoproliferative syndrome (ALPS)+ES, and 1 had Wiskott-Aldrich syndrome (WAS)+AIHA. Among the 13 primary idiopathic AIHA patients, 9 recovered following a 4-8-week course of prednisolone treatment without relapses, whereas 3 patients required a longer course of prednisolone. One AIHA patient that was very resistant to prednisolone recovered after cyclosporine A was added to the treatment. All patients with primary idiopathic AIHA were in remission for a median of 3 years (range: 4 months-10 years) at the time this manuscript was written. Among the patients with primary ES, 2 had relapses similar to the ALPS patients. Splenectomy was performed in 1 primary ES patient, who at the time this report was written was also in remission. One ALPS patient required the addition of mycophenolate mofetil due to prednisolone resistance. The WAS patient was treatment resistant and died due to septicemia. CONCLUSION: Primary AIHA in pediatric patients generally has an acute onset and good response to corticosteroids. Primary or secondary ES has a chronic or relapsing course, and treatment may require other immunosuppressive agents in addition to corticosteroids. Complications of splenectomy must not be underestimated in patients with underlying immunodeficiency. AIHA often causes considerable morbidity and mortality in WAS. PMID- 27264368 TI - Surgical and histopathological effects of topical Ankaferd(r) hemostat on major arterial vessel injury related to elevated intra-arterial blood pressure. AB - OBJECTIVE: The aim of this study was to assess the surgical and histopathological hemostatic effects of topical Ankaferd blood stopper (ABS) on major arterial vessel injury related to elevated intra-arterial blood pressure in an experimental rabbit model. METHODS: The study included 14 New Zealand rabbits. ABS was used to treat femoral artery puncture on 1 side in each animal and the other untreated side served as the control. Likewise, for abdominal aortic puncture, only 50% of the aortic injuries received topical liquid ABS and the others did not (control). The experiment was performed under conditions of normal arterial blood pressure and was repeated with a 50% increase in blood pressure. Histopathological analysis was performed in all of the studied animals. RESULTS: Mean bleeding time in the control femoral arteries was 105.0+/-18.3 s, versus 51.4+/-9.8 s (p<0.05) in those treated with ABS. Mean blood loss from the punctured control femoral arteries was 5.0+/-1.5 mg and 1.6+/-0.4 mg from those treated with ABS (p<0.05). Histopathological examination of the damaged arterial structures showed that ABS induced red blood cell aggregates. CONCLUSION: ABS administered to experimental major arterial vessel injury reduced both bleeding time and blood loss under conditions of normal and elevated intra-arterial blood pressure. ABS-induced erythroid aggregation was prominent at the vascular tissue level. These findings will inform the design of future experimental and clinical studies on the anti-bleeding and vascular repairing effects of the novel hemostatic agent ABS. PMID- 27264369 TI - ADAMTS-13 gene expression in antiphospholipid syndrome. AB - OBJECTIVE: Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent thrombosis and fetal mortality. Thrombotic microangiopathy (TMA) is an important histological finding in catastrophic APS (CAPS) and in APS patients with nephropathy. Analysis of familial thrombotic thrombocytopenic purpura patients showed that there are mutations in the ADAMTS 13 gene that lead to functional defects in the ADAMTS-13 enzyme. The aim of this study was to investigate the prevalence of the aforementioned mutations in APS, as well as to evaluate the level and activity of the ADAMTS-13 enzyme in patients with APS. METHODS: C365del, Q449stop codon, P475S, and C508Y mutations were analyzed in APS patients. Transcriptions were analyzed using real-time PCR, and the level and activity of ADAMTS-13 were analyzed via fluorogenic assay. RESULTS: None of the mutations tested were present in the patient or control groups. The level of ADAMTS-13 mRNA in the patient group was 50% lower than that in the control group. Although a significant difference in ADAMTS-13 activity was not observed between the patient and control groups, a significant association was observed with the level of ADAMTS-13 (p<0.0001). CONCLUSION: The level and activity of ADAMTS-13 were not associated with thrombotic complications, thrombocytopenia, or pregnancy complications in the patients with APS. PMID- 27264370 TI - The effect of HBB: c.*+96T>C (3'UTR +1570 T>C) on the mild b-thalassemia intermedia phenotype. AB - Hemoglobin beta (HBB): c.*+96T>C substitution is very rare among beta-globin gene mutations and its clinical significance remains to be clarified. The present study aimed to investigate the role of HBB: c.*+96T>C in the beta-thalassemia intermedia phenotype in a Turkish family. The proband and parents were screened for beta-globin gene mutations via direct sequencing. Hematological and physical examination results were recorded, and correlated according to genotype. The proband was compound heterozygous for Cod 8 (-AA) and HBB: c.*+96T>C, whereas his mother and father were heterozygous for Cod 8 (-AA) and HBB: c.*+96T>C, respectively. The father had almost normal hematological findings, whereas the mother had the typical beta-thalassemia trait phenotype. The proband was diagnosed as mild beta-thalassemia intermedia based on hepatosplenomegaly and hematological findings. To the best of our knowledge this is the first report of HBB: c.*+96T>C mutation in a Turkish family. HBB: c.* 96T>C substitution is a very rare, but clinically relevant beta-globin gene mutation. Additionally, we think that if 1 spouse is a carrier for beta-globin gene mutation the other should be screened for silent mutations, such as HBB: c.*+96T>C mutation of the beta-globin gene, even if she/he does not have any clinical or hematological signs of the beta-thalassemia trait phenotype. PMID- 27264371 TI - Eculizumab before and after allogeneic hematopoietic stem cell transplantation in a patient with paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the triad of intravascular hemolysis, venous thrombosis, and cytopenia. Treatment of PNH is generally supportive. Bone marrow transplantation is the only curative therapy for PNH, but is associated with significant morbidity and mortality. Herein, we present a patient with PNH that received eculizumab, a humanized monoclonal antibody that blocks activation of the terminal complement at C5, before and immediately following allogeneic peripheral stem cell transplantation. Prior to hematopoietic stem cell transplantation eculizumab treatment markedly reduced hemolysis and transfusion requirement; however, 1 d post transplantation a hemolytic episode occured, which was successfully stopped with eculizumab re treatment. Afterwards the patient did not require additional transfusions. The results of this study indicate that early administration of eculizumab may be a safe and effective therapy for hemolytic episodes associated with allogeneic peripheral stem cell transplantation in patients with PNH. PMID- 27264372 TI - Extramedullary plasmacytoma presenting as a mediastinal mass. AB - Extramedullary plasmacytoma (EMP) is a plasma cell neoplasm without bone marrow involvement or other systemic characteristics of multiple myeloma. Few large scale clinical studies have been conducted because of the rarity of EMP, especially when it arises from the mediastinum. Herein we report a rare case of solitary mediastinal plasmacytoma with reactive pleural effusion. A 58-year-old female presented with grade 4 dyspnea and dysphagia, with a mediastinal mass observed with on PET. CT-guided biopsy results were suggestive of IgG kappa-type EMP arising from the anterior mediastinum. The patient was treated with local radiotherapy to the mediastinum, and had clinical and radiological response s were good. Radiotherapy is an effective treatment for mediastinal EMP, but a complete workup is mandatory, including PET, as the majority of such masses coexist with multiple myeloma. PMID- 27264373 TI - Non-Hodgkin's lymphoma in a chronic myelocytic leukemia patient treated with imatinib. AB - Imatinib is an important example of tyrosine kinase inhibitors (TKIs) used in clinical practice. Imatinib blocks the ATP binding site of the Bcr-Abl fusion protein and selectively inhibits Bcr-Abl tyrosine kinase (TK) activity. Treatment of chronic myelocytic leukemia (CML) with imatinib is encouraging and it has an acceptable toxicity profile, and as such has changed the management of CML during the last decade. As with all drugs used in clinical practice, side effects of imatinib have been reported in studies with extended follow-up periods. In addition, some neoplastic disorders have been reported to occur during imatinib therapy. Herein we present a CML case that developed non-Hodgkin's lymphoma (NHL) while receiving imatinib treatment. PMID- 27264374 TI - The incidence of alpha-thalassemia in Iraqi Turks. PMID- 27264375 TI - Non-Hodgkin's lymphoma in a hemophilic patient with a traumatic hematoma. PMID- 27264376 TI - A chronic eosinophilic leukemia patient presenting with blurred vision. PMID- 27264377 TI - The frequency of FV G1691A and PT G20210A mutations in an Albanian population. PMID- 27264378 TI - Cytopenia associated with iron deficiency anemia and iron therapy: A report of two cases. PMID- 27264379 TI - Accidental intrathecal methotrexate overdose. PMID- 27264380 TI - CTLA-4 A49G polymorphism and autoimmune blood disease: A comment. PMID- 27264381 TI - Iron deficiency anemia and total antioxidant capacity. PMID- 27264382 TI - Decreased erythrocyte catalase level in iron deficiency. PMID- 27264383 TI - Partial splenic embolization versus splenectomy for the management of autoimmune hemolytic anemia: A response. PMID- 27264384 TI - A rare cause of iron deficiency anemia in a child: Lithobezoar. PMID- 27264385 TI - An unusual cause of iron deficiency anemia in a healthy man: Hijamah. PMID- 27264386 TI - Exogenous N addition enhances the responses of gross primary productivity to individual precipitation events in a temperate grassland. AB - Predicted future shifts in the magnitude and frequency (larger but fewer) of precipitation events and enhanced nitrogen (N) deposition may interact to affect grassland productivity, but the effects of N enrichment on the productivity response to individual precipitation events remain unclear. In this study, we quantified the effects of N addition on the response patterns of gross primary productivity (GPP) to individual precipitation events of different sizes (Psize) in a temperate grassland in China. The results showed that N enrichment significantly increased the time-integrated amount of GPP in response to an individual precipitation event (GPPtotal), and the N-induced stimulation of GPP increased with increasing Psize. N enrichment rarely affected the duration of the GPP response, but it significantly stimulated the maximum absolute GPP response. Higher foliar N content might play an important role in the N-induced stimulation of GPP. GPPtotal in both the N-addition and control treatments increased linearly with Psize with similar Psize intercepts (approximately 5 mm, indicating a similar lower Psize threshold to stimulate the GPP response) but had a steeper slope under N addition. Our work indicates that the projected larger precipitation events will stimulate grassland productivity, and this stimulation might be amplified by increasing N deposition. PMID- 27264388 TI - Genetic Studies on Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is a highly heterogeneous reproductive system disorder of which the aetiology is not fully understood. Previous association studies have been conducted on >100 candidate genes, which principally related to reproductive hormones, cellular metabolism and chronic inflammation. Heritable tendencies have long been recognized for pathogeneses of PCOS, and recently a genome-wide association study (GWAS) in PCOS provides new clues to understand the genetic components and pathways in PCOS physiology. However, the current knowledge of the pathogenesis of PCOS is still in its infancy. Further studies using new technologies such as next-generation sequencing (NGS) shall be useful to understand more causal variants for PCOS. PMID- 27264389 TI - Evaluation of emergency department nursing services and patient satisfaction of services. AB - AIMS AND OBJECTIVES: To identify nursing services and assess patient satisfaction in patients who present to the emergency department. BACKGROUND: Emergency nursing care is a significant determinant of patient satisfaction. Patient satisfaction is often regarded as a reliable indicator of the quality of services provided in the emergency department. DESIGN: This is a descriptive study. METHODS: Eighty-four patients who presented to the university emergency department were included in the study. The study data were collected by the Patient Information Form and the Satisfaction Level Form. RESULTS: Emergency nursing services, including history taking, assessing vital signs, preparing the patient for an emergency intervention, oxygen therapy, drug delivery and blood serum infusion were shown to be more commonly provided compared with other services such as counselling the patients and the relatives about their care or delivering educational and psychosocial services. However, 78.6% of the patients were satisfied with their nursing services. The highest satisfaction rates were observed in the following sub-dimensions of the Satisfaction Level Form: availability of the nurse (82.1%), behaviour of the nurse towards the patient (78.6%) and the frequency of nursing rounds (77.4%). CONCLUSIONS: The most common practices performed by nurses in the emergency department were physical nursing services. Patient satisfaction was mostly associated with the availability of nurses when they were needed. Our results suggest that in addition to the physical care, patients should also receive education and psychosocial care in the emergency department. RELEVANCE TO CLINICAL PRACTICE: We believe that this study will contribute to the awareness and understanding of principles and concepts of emergency nursing, extend the limits of nursing knowledge and abilities, and improve and maintain the quality of clinical nursing education and practice to train specialist nurses with high levels of understanding in ethical, intellectual, administrative, investigative and professional issues. PMID- 27264387 TI - Maternal influenza and birth outcomes: systematic review of comparative studies. AB - BACKGROUND: Although pregnant women are considered at high risk for severe influenza disease, comparative studies of maternal influenza and birth outcomes have not been comprehensively summarised. OBJECTIVE: To review comparative studies evaluating maternal influenza disease and birth outcomes. SEARCH STRATEGY: We searched bibliographic databases from inception to December 2014. SELECTION CRITERIA: Studies of preterm birth, small-for-gestational-age (SGA) birth or fetal death, comparing women with and without clinical influenza illness or laboratory-confirmed influenza infection during pregnancy. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed study quality. MAIN RESULTS: Heterogeneity across 16 studies reporting preterm birth precluded meta-analysis. In a subgroup of the highest-quality studies, two reported significantly increased preterm birth (risk ratios (RR) from 2.4 to 4.0) following severe 2009 pandemic H1N1 (pH1N1) influenza illness, whereas those assessing mild-to-moderate pH1N1 or seasonal influenza found no association. Five studies of SGA birth showed no discernible patterns with respect to influenza disease severity (pooled odds ratio 1.24; 95% CI 0.96-1.59). Two fetal death studies were of sufficient quality and size to permit meaningful interpretation. Both reported an increased risk of fetal death following maternal pH1N1 disease (RR 1.9 for mild-to-moderate disease and 4.2 for severe disease). CONCLUSIONS: Comparative studies of preterm birth, SGA birth and fetal death following maternal influenza disease are limited in number and quality. An association between severe pH1N1 disease and preterm birth and fetal death was reported by several studies; however, these limited data do not permit firm conclusions on the magnitude of any association. TWEETABLE ABSTRACT: Comparative studies are limited in quality but suggest severe pandemic H1N1 influenza increases preterm birth. PMID- 27264391 TI - A Case of Abdominal Discomfort Caused by Benign Multicystic Peritoneal Mesothelioma. PMID- 27264390 TI - Selective Expression of Osteopontin in ALS-resistant Motor Neurons is a Critical Determinant of Late Phase Neurodegeneration Mediated by Matrix Metalloproteinase 9. AB - Differential vulnerability among motor neuron (MN) subtypes is a fundamental feature of amyotrophic lateral sclerosis (ALS): fast-fatigable (FF) MNs are more vulnerable than fast fatigue-resistant (FR) or slow (S) MNs. The reason for this selective vulnerability remains enigmatic. We report here that the extracellular matrix (ECM) protein osteopontin (OPN) is selectively expressed by FR and S MNs and ALS-resistant motor pools, whereas matrix metalloproteinase-9 (MMP-9) is selectively expressed by FF MNs. OPN is secreted and accumulated as extracellular granules in ECM in three ALS mouse models and a human ALS patient. In SOD1(G93A) mice, OPN/MMP-9 double positivity marks remodeled FR and S MNs destined to compensate for lost FF MNs before ultimately dying. Genetic ablation of OPN in SOD1(G93A) mice delayed disease onset but then accelerated disease progression. OPN induced MMP-9 up-regulation via alphavbeta3 integrin in ChAT-expressing Neuro2a cells, and also induced CD44-mediated astrocyte migration and microglial phagocytosis in a non-cell-autonomous manner. Our results demonstrate that OPN expressed by FR/S MNs is involved in the second-wave neurodegeneration by up regulating MMP-9 through alphavbeta3 integrin in the mouse model of ALS. The differences in OPN/MMP-9 expression profiles in MN subsets partially explain the selective MN vulnerability in ALS. PMID- 27264392 TI - The Birds, the Bees, and Inflammatory Bowel Disease: Preconception Care in Inflammatory Bowel Disease. PMID- 27264394 TI - Weight Change and Weight Cycling Are Not Associated With Risk of Barrett's Esophagus. PMID- 27264393 TI - Inverse Association Between Gluteofemoral Obesity and Risk of Barrett's Esophagus in a Pooled Analysis. AB - BACKGROUND & AIMS: Gluteofemoral obesity (determined by measurement of subcutaneous fat in the hip and thigh regions) could reduce risks of cardiovascular and diabetic disorders associated with abdominal obesity. We evaluated whether gluteofemoral obesity also reduces the risk of Barrett's esophagus (BE), a premalignant lesion associated with abdominal obesity. METHODS: We collected data from non-Hispanic white participants in 8 studies in the Barrett's and Esophageal Adenocarcinoma Consortium. We compared measures of hip circumference (as a proxy for gluteofemoral obesity) from cases of BE (n = 1559) separately with 2 control groups: 2557 population-based controls and 2064 individuals with gastroesophageal reflux disease (GERD controls). Study-specific odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using individual participant data and multivariable logistic regression and combined using a random-effects meta-analysis. RESULTS: We found an inverse relationship between hip circumference and BE (OR per 5-cm increase, 0.88; 95% CI, 0.81-0.96), compared with population-based controls in a multivariable model that included waist circumference. This association was not observed in models that did not include waist circumference. Similar results were observed in analyses stratified by frequency of GERD symptoms. The inverse association with hip circumference was statistically significant only among men (vs population-based controls: OR, 0.85; 95% CI, 0.76-0.96 for men; OR, 0.93; 95% CI, 0.74-1.16 for women). For men, within each category of waist circumference, a larger hip circumference was associated with a decreased risk of BE. Increasing waist circumference was associated with an increased risk of BE in the mutually adjusted population-based and GERD control models. CONCLUSIONS: Although abdominal obesity is associated with an increased risk of BE, there is an inverse association between gluteofemoral obesity and BE, particularly among men. PMID- 27264395 TI - Plantar pressure measurements and running-related injury: A systematic review of methods and possible associations. AB - Pressure-sensitive measuring devices have been identified as appropriate tools for measuring an array of parameters during running. It is unclear which biomechanical characteristics relate to running-related injury (RRI) and which data-processing techniques are most promising to detect this relationship. This systematic review aims to identify pertinent methodologies and characteristics measured using plantar pressure devices, and to summarise their associations with RRI. PubMed, Embase, CINAHL, ScienceDirect and Scopus were searched up until March 2015. Retrospective and prospective, biomechanical studies on running using any kind of pressure-sensitive device with RRI as an outcome were included. All studies involving regular or recreational runners were considered. The study quality was assessed and the measured parameters were summarised. One low quality, two moderate quality and five high quality studies were included. Five different subdivisions of plantar area were identified, as well as five instants and four phases of measurement during foot-ground contact. Overall many parameters were collated and subdivided as plantar pressure and force, plantar pressure and force location, contact area, timing and stride parameters. Differences between the injured and control group were found for mediolateral and anteroposterior displacement of force, contact area, velocity of force displacement, relative force-time integral, mediolateral force ratio, time to peak force and inter-stride correlative patterns. However, no consistent results were found between studies and no biomechanical risk patterns were apparent. Additionally, conflicting findings were reported for peak force in three studies. Based on these observations, we provide suggestions for improved methodology measurement of pertinent parameters for future studies. PMID- 27264396 TI - Benefits of multi-session balance and gait training with multi-modal biofeedback in healthy older adults. AB - Real-time balance-relevant biofeedback from a wearable sensor can improve balance in many patient populations, however, it is unknown if balance training with biofeedback has lasting benefits for healthy older adults once training is completed and biofeedback removed. This study was designed to determine if multi session balance training with and without biofeedback leads to changes in balance performance in healthy older adults; and if changes persist after training. 36 participants (age 60-88) were randomly divided into two groups. Both groups trained on seven stance and gait tasks for 2 consecutive weeks (3*/week) while trunk angular sway and task duration were monitored. One group received real-time multi-modal biofeedback of trunk sway and a control group trained without biofeedback. Training effects were assessed at the last training session, with biofeedback available to the feedback group. Post-training effects (without biofeedback) were assessed immediately after, 1-week, and 1-month post-training. Both groups demonstrated training effects; participants swayed less when standing on foam with eyes closed (EC), maintained tandem-stance EC longer, and completed 8 tandem-steps EC faster and with less sway at the last training session. Changes in sway and duration, indicative of faster walking, were also observed after training for other gait tasks. While changes in walking speed persisted post training, few other post-training effects were observed. These data suggest there is little added benefit to balance training with biofeedback, beyond training without, in healthy older adults. However, transient use of wearable balance biofeedback systems as balance aides remains beneficial for challenging balance situations and some clinical populations. PMID- 27264397 TI - Augmented feedback of COM and COP modulates the regulation of quiet human standing relative to the stability boundary. AB - The experiment manipulated real-time kinematic feedback of the motion of the whole body center of mass (COM) and center of pressure (COP) in anterior posterior (AP) and medial-lateral (ML) directions to investigate the variables actively controlled in quiet standing of young adults. The feedback reflected the current 2D postural positions within the 2D functional stability boundary that was scaled to 75%, 30% and 12% of its original size. The findings showed that the distance of both COP and COM to the respective stability boundary was greater during the feedback trials compared to a no feedback condition. However, the temporal safety margin of the COP, that is, the virtual time-to-contact (VTC), was higher without feedback. The coupling relation of COP-COM showed stable in phase synchronization over all of the feedback conditions for frequencies below 1Hz. For higher frequencies (up to 5Hz), there was progressive reduction of COP COM synchronization and local adaptation under the presence of augmented feedback. The findings show that the augmented feedback of COM and COP motion differentially and adaptively influences spatial and temporal properties of postural motion relative to the stability boundary while preserving the organization of the COM-COP coupling in postural control. PMID- 27264398 TI - Effect of gait retraining for reducing ambulatory knee load on trunk biomechanics and trunk muscle activity. AB - The purpose of this study was to test the hypothesis that walking with increased medio-lateral trunk sway is associated with lower external knee adduction moment and lower extremity muscle activation, and higher external ipsilateral trunk moment and trunk muscle activity than walking with normal trunk sway in healthy participants. Fifteen participants performed walking trials with normal and increased medio-lateral trunk sway. Maximum trunk sway, first maximum knee adduction moment, lateral trunk bending moment, and bilateral vastus medialis, vastus lateralis, gluteus medius, rectus abdominis, external oblique and erector spinae muscle activity were computed. Walking with increased trunk sway was associated with lower maximum knee adduction moment (95% confidence interval (CI): 0.50-0.62Nm/kg vs. 0.62-0.76Nm/kg; P<.001) and ipsilateral gluteus medius ( 17%; P=.014) and erector spinae muscle activity (-24%; P=.004) and greater maximum lateral trunk bending moment (+34%; P<.001) and contralateral external oblique muscle activity (+60%; P=.009). In all participants, maximum knee adduction moment was negatively correlated and maximum trunk moment was positively correlated with maximum trunk sway. The results of this study suggest that walking with increased trunk sway not only reduces the external knee adduction moment but also alters and possibly increases the load on the trunk. Hence, load-altering biomechanical interventions should always be evaluated not only regarding their effects on the index joint but on other load-bearing joints such as the spine. PMID- 27264399 TI - The influence of gait speed on the stability of walking among the elderly. AB - Walking speed is a basic factor to consider when walking exercises are prescribed as part of a training programme. Although associations between walking speed, step length and falling risk have been identified, the relationship between spontaneous walking pattern and falling risk remains unclear. The present study, therefore, examined the stability of spontaneous walking at normal, fast and slow speed among elderly (67.5+/-3.23) and young (21.4+/-1.31) individuals. In all, 55 participants undertook a test that involved walking on a plantar pressure platform. Foot-ground contact data were used to calculate walking speed, step length, pressure impulse along the plantar-impulse principal axis and pressure record of time series along the plantar-impulse principal axis. A forward dynamics method was used to calculate acceleration, velocity and displacement of the centre of mass in the vertical direction. The results showed that when the elderly walked at different speeds, their average step length was smaller than that observed among the young (p=0.000), whereas their anterior/posterior variability and lateral variability had no significant difference. When walking was performed at normal or slow speed, no significant between-group difference in cadence was found. When walking at a fast speed, the elderly increased their stride length moderately and their cadence greatly (p=0.012). In summary, the present study found no correlation between fast walking speed and instability among the elderly, which indicates that healthy elderly individuals might safely perform fast-speed walking exercises. PMID- 27264400 TI - Complexity of human gait pattern at different ages assessed using multiscale entropy: From development to decline. AB - Multiscale entropy (MSE) has been applied in biomechanics to evaluate gait stability during human gait and was found to be a promising method for evaluating fall risk in elderly and/or pathologic subjects. The hypothesis of this work is that gait complexity is a relevant parameter of gait development during life, decreasing from immature to mature gait and then increasing again during old age. In order to verify this hypothesis, MSE was applied on trunk acceleration data collected during gait of subjects of different ages: toddlers at the onset of walking, pre-scholar and scholar children, adolescents, young adults, adults and elderlies. MSE was estimated by calculating sample entropy (SEN) on raw unfiltered data of L5 acceleration along the three axes, using values of tau ranging from 1 to 6. In addition, other performance parameters (cadence, stride time variability and harmonic ratio) were evaluated. The results followed the hypothesized trend when MSE was applied on the vertical and/or anteroposterior axis of trunk acceleration: an age effect was found and adult SEN values were significantly different from children ones. From young adults to elderlies a slight increase in SEN values was shown although not statistically significant. While performance gait parameters showed adolescent gait similar to the one of adults, SEN highlighted that their gait maturation is not complete yet. In conclusion, present results suggest that the complexity of gait, evaluated on the sagittal plane, can be used as a characterizing parameter of the maturation of gait control. PMID- 27264401 TI - An optimized design of in-shoe heel lifts reduces plantar pressure of healthy males. AB - Conventional heel lift with a flat surface increases the risk of foot problems related to higher plantar pressure and decreased stability. In this study, an optimized design of in-shoe heel lifts developed to maintain the midfoot function was tested to investigate if the plantar pressure distribution was improved. The design was based on three dimensional foot plantar contour which was captured by an Infoot 3D scanning system while the heel was elevated by a heel wedge. To facilitate midfoot function, an arch support was designed to support the lateral longitudinal arch, while allowing functional movement of the medial longitudinal arch. Twenty healthy male subjects were asked to walk along an 8m walkway while wearing high-cut footwear with and without the optimized heel lift. Peak pressure, contact area and force-time integral were measured using the Pedar insole system. Range and velocity of medial-lateral center of pressure during forefoot contact phase and foot flat phase were collected using a Footscan pressure plate. Compared to the shoe only condition, peak pressure under the rearfoot decreased with the optimized heel lift, while no increase of peak pressure was observed under the forefoot and midfoot regions, indicating improved plantar pressure distribution. The findings of this study suggest that this optimized heel lift has better biomechanical performance than a conventional flat heel lift. Results from this study may have implications for insole and shoe last design, especially for people who need additional heel height without sacrificing midfoot function. PMID- 27264402 TI - Symmetry in vertical ground reaction force is not related to walking and balance difficulties in people with multiple sclerosis. AB - Analysis of vertical ground reaction force (GRF) symmetry may benefit people with multiple sclerosis (PwMS) since it can detect important differences in gait mechanics which have not previously been discussed in the related literature. Therefore, the primary objective of the current study was to determine whether symmetry of the vertical GRF during gait is associated with validated gait and balance tests in PwMS. Additionally, we examined whether the symmetry of the vertical GRF differs between MS fallers, non-fallers and between neurological disability levels. Gait and balance data were collected from 402 PwMS (249 women) with a mean age of 42.1 (S.D=14.1) years. Vertical GRF parameters were obtained using the Zebris FDM-T Treadmill (Zebris Medical GmbH, Germany). Clinical gait and balance tests included the 2 and 6-min Walk Test, Timed Up and Go Test, Timed 25 Foot Walk, Four Square Step Test, Multiple Sclerosis Walking Scale questionnaire, Modified Fatigue Impact Scale and the Falls Efficacy Scale International questionnaire. The vertical GRF symmetry index score of the total sample was 3.7 (SD=3.1). In terms of fall status, non-significant differences were observed between the fallers and non-faller groups and between the neurological disability subgroups. Non-significant correlation scores were found between the vertical GRF symmetry index, all clinical walking and balance tests and self-reported questionnaires. We suggest clinicians, especially those involved in physical rehabilitation, accord low priority to this gait phenomenon in the MS population. PMID- 27264403 TI - Development of gait performance and dynamic hip and knee joint loading after containment improving surgery in patients with Legg-Calve-Perthes disease. AB - Current surgery outcome evaluations in patients with Legg-Calve-Perthes disease (LCPD) are usually based on static radiological changes. The aim of the present study was to assess the development of characteristic gait parameters and passive hip range of motion (ROM) measurements during the postoperative period up to healed stage of the femoral head represented by Stulberg classification. Twelve children (10 male, 2 female) with unilateral diagnosis of LCPD and 19 healthy control subjects at the same age participated in this prospective longitudinal study. Instrumented gait analysis was performed preoperatively, 13.4 (+/-1.7), and 28.0 (+/-4.4) months postoperatively. At final follow-up, the mean leg length of the involved side was reduced by 1.10 (+/-0.53)cm compared to the non-involved side. In addition, a significant reduction in maximum knee flexion (-26%, p=0.037) and knee flexion/extension ROM (-26%, p=0.017) in stance was still present in the patient group compared to controls indicating a "stiff knee gait pattern". In contrast, the sagittal plane hip parameters, the ipsilateral trunk lean toward the involved stance limb, and the knee and hip joint loading during gait normalized during the postoperative period. The results of the present study should motivate further exploration if patients with LCPD stiffen their knees to compensate for leg length discrepancy. Besides the standard radiological evaluation of the surgery outcome, instrumented gait analysis is a valuable method of recording functional deficits and early recognition of the need for physiotherapeutic treatment or insole supply in patients with LCPD. PMID- 27264404 TI - The effects of altering attentional demands of gait control on the variability of temporal and kinematic parameters. AB - The purpose of this study was to investigate the effects of cognitive and visuomotor tasks on gait control in terms of the magnitude and temporal structure of the variability in stride time and lower-limb kinematics measured using inertial sensors. Fourteen healthy young subjects walked on a treadmill for 15min at a self-selected gait speed in the three conditions: normal walking without a concurrent task; walking while performing a cognitive task; and walking while performing a visuomotor task. The time series data of stride time and peak shank angular velocity were generated from acceleration and angular velocity data recorded from both shanks. The mean, coefficient of variation, and fractal scaling exponent alpha of the time series of these variables and the standard deviation of shank angular velocity over the entire stride cycle were calculated. The cognitive task had an effect on long-range correlations in stride time but not on lower-limb kinematics. The temporal structure of variability in stride time became more random in the cognitive task. The visuomotor task had an effect on lower-limb kinematics. Subjects controlled their swing limb with greater variability and had a more complex adaptive lower-limb movement pattern in the visuomotor task. The effects of the dual tasks on gait control were different for stride time and lower-limb kinematics. These findings suggest that the temporal structure of variability and lower-limb kinematics are useful parameters to detect a change in gait pattern and provide further insight into gait control. PMID- 27264405 TI - Effect of sloped walking on lower limb muscle forces. AB - Lower limb joint loadings are increased during sloped walking compared to level walking and muscle forces are major contributors to lower limb joint forces. Therefore, the aim of this study was to analyze lower limb muscle forces during sloped walking at different inclinations. Eighteen healthy male participants (27.0+/-4.7y, 1.80+/-0.05m, 74.5+/-8.2kg) walked at a pre-set speed of 1.1m/s on a ramp at the inclinations of 0 degrees , +/-6 degrees , +/-12 degrees and +/-18 degrees . Kinematic data were captured with a motion capture system and kinetic data were recorded with two force plates imbedded into the ramp. A musculoskeletal model was used to compute lower limb muscle forces (normalized to body weight and gait cycle duration). During downhill walking gluteus maximus, quadriceps, soleus, peroneus and tibialis anterior muscle forces increased (p<=0.002) compared to level walking, while gluteus minimus, piriformis, adductor, iliopsoas, hamstrings and gastrocnemii muscle forces decreased (p<=0.002). Uphill walking decreased gluteus minimus, iliopsoas and tibialis anterior muscle forces (p<=0.002), while all other muscle forces increased (p<=0.002, except gluteus medius). Joint-muscle-force waveforms provided information on possible muscle contributions to joint compression forces. The most important muscles were: gluteus medius for hip forces, quadriceps and gastrocnemii for tibiofemoral forces, quadriceps for patellofemoral forces and triceps surae for ankle forces. The contribution of each muscle changed with the inclination during sloped walking compared to level walking. The current study provided important information on muscle forces during sloped walking that can be useful for rehabilitation and training procedures. PMID- 27264406 TI - Postural seated balance in children can be assessed with good reliability. AB - BACKGROUND: Seated postural stability can be measured using Tekscan, CONFORMat. Standing postural stability has gained great clinical and, research value by use of different force platforms with mostly good reliability. No reliability testing or biologic variation assessment has been documented regarding seated balance. This study determines the reliability of the parameters of seated balance in healthy children using the Tekscan CONFORMat equipment. METHODS: Sixty-six healthy children completed six measurements of seating position the first three with the child seated in a relaxed normal back position and the next three with the child seated in a complete up-right back position. The SAM software calculated five default parameters of balance (area, distance, variability, antero-posterior (AP) excursion and left-right excursion). RESULTS: Reliability parameters were assessed by one-way analysis of variance intra-class correlation (ICC) proving excellent reliability for relaxed and up-right back position with respect to distance (0.75/0.84) and good reliability with respect to variability (0.61/0.62) and area (0.61/0.60). AP excursion (0.41/0.59) and left-right excursion (0.54/0.24) showed fair to poor reliability. CONCLUSION: In conclusion, two of the five default parameters of balance used in the Tekscan CONFORMat system are direction-independent parameters and have been found reproducible for measuring seated balance in children. This study can be used as reference for comparisons of seated balance in children with affected seated postural control and for evaluating a clinical treatment effect. PMID- 27264407 TI - Joint power and kinematics coordination in load carriage running: Implications for performance and injury. AB - Investigating the impact of incremental load magnitude on running joint power and kinematics is important for understanding the energy cost burden and potential injury-causative mechanisms associated with load carriage. It was hypothesized that incremental load magnitude would result in phase-specific, joint power and kinematic changes within the stance phase of running, and that these relationships would vary at different running velocities. Thirty-one participants performed running while carrying three load magnitudes (0%, 10%, 20% body weight), at three velocities (3, 4, 5m/s). Lower limb trajectories and ground reaction forces were captured, and global optimization was used to derive the variables. The relationships between load magnitude and joint power and angle vectors, at each running velocity, were analyzed using Statistical Parametric Mapping Canonical Correlation Analysis. Incremental load magnitude was positively correlated to joint power in the second half of stance. Increasing load magnitude was also positively correlated with alterations in three dimensional ankle angles during mid-stance (4.0 and 5.0m/s), knee angles at mid-stance (at 5.0m/s), and hip angles during toe-off (at all velocities). Post hoc analyses indicated that at faster running velocities (4.0 and 5.0m/s), increasing load magnitude appeared to alter power contribution in a distal-to-proximal (ankle->hip) joint sequence from mid-stance to toe-off. In addition, kinematic changes due to increasing load influenced both sagittal and non-sagittal plane lower limb joint angles. This study provides a list of plausible factors that may influence running energy cost and injury risk during load carriage running. PMID- 27264408 TI - Accuracy of KinectOne to quantify kinematics of the upper body. AB - Motion analysis systems deliver quantitative information, e.g. on the progress of rehabilitation programs aimed at improving range of motion. Markerless systems are of interest for clinical application because they are low-cost and easy to use. The first generation of the KinectTM sensor showed promising results in validity assessment compared to an established marker-based system. However, no literature is available on the validity of the new 'KinectTM for Xbox one' (KinectOne) in tracking upper body motion. Consequently, this study was conducted to analyze the accuracy and reliability of the KinectOne in tracking upper body motion. Twenty subjects performed shoulder abduction in frontal and scapula plane, flexion, external rotation and horizontal flexion in two conditions (sitting and standing). Arm and trunk motion were analyzed using the KinectOne and compared to a marker-based system. Comparisons were made using Bland Altman statistics and Coefficient of Multiple Correlation. On average, differences between systems of 3.9+/-4.0 degrees and 0.1+/-3.8 degrees were found for arm and trunk motion, respectively. Correlation was higher for the arm than for the trunk motion. Based on the observed bias, the accuracy of the KinectOne was found to be adequate to measure arm motion in a clinical setting. Although trunk motion showed a very low absolute bias between the two systems, the KinectOne was not able to track small changes over time. Before the KinectOne can find clinical application, further research is required analyzing whether validity can be improved using a customized tracking algorithm or other sensor placement, and to analyze test-retest reliability. PMID- 27264409 TI - Effects of leg muscle fatigue on gait in patients with Parkinson's disease and controls with high and low levels of daily physical activity. AB - Patients with Parkinson's disease (PD) are more susceptible to muscle fatigue, which can damage their gait. Physical activity can improve muscle condition, which is an important aspect during walking. The aim of this study was to analyze the effects of lower limb muscle fatigue on gait in patients with PD and healthy individuals, grouped according to physical activity level. Twenty Patients with PD (PD group) and 20 matched individuals (control group) were distributed according to physical activity level into four subgroups of ten individuals (active and inactive). Participants performed three walking trials before and after lower limb muscle fatigue, induced by a repeated sit-to-stand task on a chair. Kinematic (stride length, width, duration, velocity and percentage of time in double support) and kinetic (propulsive and breaking anterior-posterior and medio-lateral impulse) gait parameters were analyzed. In both groups, participants increased stride length and velocity and decreased stride duration and braking vertical impulse after lower limb muscle fatigue. The PD groups presented higher step width and percentage of double time support than the control groups before muscle fatigue. The control groups increased step width and decreased percentage of time in double support, while the PD groups did not change these parameters. For physical activity level, active individuals presented longer stride length, greater stride velocity, higher braking and propulsive anterior-posterior impulse and shorter step width than inactive individuals. Groups sought more balance and safety after lower limb muscle fatigue. Physical activity level does not appear to modify the effects of lower limb muscle fatigue during unobstructed walking in individuals with PD or controls. PMID- 27264411 TI - Influence of virtual height exposure on postural reactions to support surface translations. AB - As fear of falling is related to the increased likelihood of falls, it is important to understand the effects of threat-related factors (fear, anxiety and confidence) on dynamic postural reactions. Previous studies designed to examine threat effects on dynamic postural reactions have methodological limitations and lack a comprehensive analysis of simultaneous kinetic, kinematic and electromyographical recordings. The current study addressed these limitations by examining postural reactions of 26 healthy young adults to unpredictable anterior posterior support-surface translations (acceleration=0.6m/s(2), constant velocity=0.25m/s, total displacement=0.75m) while standing on a narrow virtual surface at Low (0.4cm) and High (3.2m) virtual heights. Standing at virtual height increased fear and anxiety, and decreased confidence. Prior to perturbations, threat led to increased tonic muscle activity in tibialis anterior, resulting in a higher co-contraction index between lower leg muscles. For backward perturbations, muscle activity in the lower leg and arm, and center of pressure peak displacements, were earlier and larger when standing at virtual height. In addition, arm flexion significantly increased while leg, trunk and center of mass displacements remained unchanged across heights. When controlling for leaning, threat-related factors can influence the neuro-mechanical responses to an unpredictable perturbation, causing specific characteristics of postural reactions to be facilitated in young adults when their balance is threatened. PMID- 27264410 TI - Supraspinal control of automatic postural responses in people with multiple sclerosis. AB - The neural underpinnings of delayed automatic postural responses in people with multiple sclerosis (PwMS) are unclear. We assessed whether white matter pathways of two supraspinal regions (the cortical proprioceptive Broadman's Area-3; and the balance/locomotor-related pedunculopontine nucleus) were related to delayed postural muscle response latencies in response to external perturbations. 19 PwMS (48.8+/-11.4years; EDSS=3.5 (range: 2-4)) and 12 healthy adults (51.7+/ 12.2years) underwent 20 discrete, backward translations of a support surface. Onset latency of agonist (medial-gastrocnemius) and antagonist (tibialis anterior) muscles were assessed. Diffusion tensor imaging assessed white-matter integrity (i.e. radial diffusivity) of cortical proprioceptive and balance/locomotor-related tracts. Latency of the tibialis anterior, but not medial gastrocnemius was larger in PwMS than control subjects (p=0.012 and 0.071, respectively). Radial diffusivity of balance/locomotor tracts was higher (worse) in PwMS than control subjects (p=0.004), and was significantly correlated with tibialis (p=0.002), but not gastrocnemius (p=0.06) onset latency. Diffusivity of cortical proprioceptive tracts was not correlated with muscle onset. Lesions in supraspinal structures including the pedunculopontine nucleus balance/locomotor network may contribute to delayed onset of postural muscle activity in PwMS, contributing to balance deficits in PwMS. PMID- 27264414 TI - Specific Problems With Accidental Deaths in Japan - Cardiac Arrest From Hot Baths and Foreign Body Airway Obstruction in Elders. PMID- 27264412 TI - Construct validity of the walk ratio as a measure of gait control in people with multiple sclerosis without mobility aids. AB - Ambulatory limitations are a key component of disability in people with multiple sclerosis (PwMS). Various tools are employed to assess walking performance in PwMS; however, no ideal measure has as yet been attained. In this situation, a walk ratio might be more advantageous compared with other gait measures. The walk ratio, a simple index for describing temporal and spatial co-ordination, denotes the relationship between step length and cadence during walking. Hence, the primary objective of this study was to determine the relationship between the walk ratio and measures of other theoretically related constructs. The walk ratio was studied using the GAITRiteTM system (CIR Systems, Inc. Havertown, USA). The study group included 229 PwMS (143 women) and a mean disease duration of 5.8 (SD=7.1) years. The walk ratio score of the total sample was 5.3 (SD=0.8). Significant differences based on the expanded disability status scale (EDSS) scores (F=11.616, P<0.001) were observed between the neurological disability subgroups. Scores of the very mild (EDSS 0-2.0), mild (EDSS 2.5-4.0) and moderate (EDSS 4.5-5.5) groups were 5.5 (SD=0.7), 5.2 (SD=0.7), 4.9 (SD=0.9), respectively. In terms of fall status, the MS fallers demonstrated a significant lower walk ratio compared to the MS non-fallers; 5.1 (SD=0.8) vs. 5.5 (SD=0.7); P<0.001. Modest significant correlation scores were found between walk ratio and ambulation tests. Scores were slightly higher in the short walking tests, timed 25-foot walk and timed up and go tests (Pearson's rho=0.369, 0.364) compared to the 6 and 2-min walk time tests (Pearson's rho=0.344, 0.308). Collectively, the current study supports the construct validity of the walk ratio index in PwMS without mobility aids. PMID- 27264413 TI - Effects of 4 Statins on Regression of Coronary Plaque in Acute Coronary Syndrome. AB - BACKGROUND: There is no information on differences in the effects of moderate- and low-intensity statins on coronary plaque in patients with acute coronary syndrome (ACS). The aim of this study was to compare the effects of 4 different statins in patients with ACS, using intravascular ultrasound (IVUS). METHODS AND RESULTS: A total of 118 patients with ACS who underwent IVUS before percutaneous coronary intervention and who were found to have mild to moderate non-culprit coronary plaques were randomly assigned to receive either 20 mg/day atorvastatin or 4 mg/day pitavastatin (moderate-intensity statin therapy), or 10 mg/day pravastatin or 30 mg/day fluvastatin (low-intensity statin therapy). IVUS at baseline and at end of 10-month treatment was available in 102 patients. Mean percentage change in plaque volume (PV) was -11.1+/-12.8%, -8.1+/-16.9%, 0.4+/ 16.0%, and 3.1+/-20.0% in the atorvastatin, pitavastatin, pravastatin, and fluvastatin groups, respectively (P=0.007, ANOVA). Moderate-intensity statin therapy induced regression of PV, whereas low-intensity statin therapy produced insignificant progression (-9.6% vs. 1.8%, P<0.001). On multivariate linear regression analysis, moderate-intensity statin therapy (P=0.02) and uric acid at baseline (P=0.02) were significant determinants of large percent PV reduction. LDL-C at follow-up did not correlate with percent PV change. CONCLUSIONS: Moderate-intensity statin therapy induced regression of coronary PV, whereas low intensity statin therapy resulted in slight progression of coronary PV in patients with ACS. (Circ J 2016; 80: 1634-1643). PMID- 27264415 TI - Insomnia in Heart Failure. PMID- 27264416 TI - Regional Differences in Warfarin Therapy Among Japanese Patients With Atrial Fibrillation. PMID- 27264417 TI - Systemic Inflammation Is a Key Factor for Mortality Risk Stratification in Chronic Kidney Disease Patients With Coronary Artery Calcification. PMID- 27264418 TI - Letter to the Editor. PMID- 27264419 TI - Distinctive skeletal phenotype in high bone mass osteogenesis imperfecta due to a COL1A2 cleavage site mutation. PMID- 27264420 TI - IL-1beta/NF-kb signaling promotes colorectal cancer cell growth through miR 181a/PTEN axis. AB - To date, the role of miRNA in tumorigenesis has been largely reported. It was found that miR-181a may be involved in the tumorigenesis of colon cancer. The purpose of this study was to investigate the mechanism of miR-181a in colon cancer carcinogenesis. The expression levels of IL-1beta, NF-kappaB (RelA), and miR-181a in colon cancer tissue were higher than that in normal control tissue when assessed by real-timePCR. In addition, it was found that IL-1beta induced the expression of miR-181a. The expression of PTEN was regulated by IL-1beta stimulated miR-181a expression. In a PTEN reporter plasmid, miR-181a binding site mutations were introduced. By using a luciferase reporter assay, it was found that wild type reported activity was lower than that of the mutant registration system activity. Furthermore, a siRNA strategy was used to find that IL-1B regulates miR-181a expression via NF-kappaB and then regulates PTEN expression. Consequently, repression of PTEN by miR-181a promotes colon cancer cell proliferation. Taken together, our data support a critical role for NF-kappaB dependent upregulation of miR-181a; this represents a new pathway for the repression of PTEN and the promotion of cell proliferation upon IL-1beta induction. PMID- 27264421 TI - A Polyoxometalate Cluster Paradigm with Self-Adaptive Electronic Structure for Acidity/Reducibility-Specific Photothermal Conversion. AB - Photothermal conversion is one of the most important keys in the fields of solar collection, photo-hyperthermia, etc., and its performance is highly dependent on the photothermal conversion materials used. Especially in cancer photo hyperthermia, the presently available small-molecule- or nanomaterial-based agents still suffer from numerous drawbacks, such as nonspecific accumulation and inevitable side effects on normal tissues. Here we identify a Mo-based polyoxometalate cluster that can change its dimension from small (1 nm) to big (tens of nanometer), favoring its intratumoral accumulation, and enhance photothermal conversion in response to the intratumoral acidity and reducibility, demonstrating a previously unrealized tumor-specific photo-hyperthermia. Distinct from the well-researched nano-based agents, a unique electronic structure of this cluster has been identified as the origin of the observed acidity-induced self assembly and reduction-promoted NIR absorbance. In addition to providing a promising clinical agent, this finding is expected to establish a new physicochemical paradigm for photothermal materials design based on clusters. PMID- 27264422 TI - The 57(th) Annual Meeting of the JSGE. PMID- 27264423 TI - Clinical management of functional dyspepsia -Is the management changed after publication of Japanese FD guideline? PMID- 27264424 TI - New horizon of the pathophysiology of functional dyspepsia. PMID- 27264425 TI - Diagnostic and therapeutic advances in functional dyspepsia (FD). PMID- 27264426 TI - Expected development of therapy for functional dyspepsia -focusing on psychosomatic approach. PMID- 27264427 TI - A case of ectopic pancreatic cancer in the mesentery of the jejunum. AB - We report a rare case of ectopic pancreatic cancer in the mesentery of the jejunum. A 68-year-old man presented with left abdominal pain. Contrast-enhanced abdominal CT revealed a 3-cm tumor in the mesentery near the ligament of Treitz. He had required surgery for gastric cancer 28 years ago;therefore, surgery was scheduled on the suspicion of recurrence/metastasis of gastric cancer or gastrointestinal stromal tumor (GIST) and mesenteric tumors. A tumor was observed in the mesentery of the jejunum of the ligament of Treitz. Histopathology showed a moderately differentiated adenocarcinoma, and it was diagnosed as a primary ductal pancreatic cancer (Heinrich classification, not classifiable). PMID- 27264428 TI - A case of gastric crystal-storing histiocytosis. AB - A 54-year-old male patient underwent upper gastrointestinal endoscopy, which revealed a 25-mm brown region in the angular section of the greater curvature of the stomach. The region was histologically determined to be gastric mucosa with an accumulation of histiocytes containing eosinophilic substances in the cytoplasm and chronic inflammatory cell infiltration. Histiocytes were immunohistologically positive for CD68, IgG, and kappa. Based on these findings, the patient was diagnosed with gastric crystal-storing histiocytosis comprised of histiocytes phagocytosing IgG-kappa-type immunoglobulin. This is a rare disease of which there have been no previous reports that included long-term follow-up. Here, we report the case with a literature review. PMID- 27264429 TI - A case of Menetrier's disease seemingly caused by hilar cholangiocarcinoma. AB - A 54-year-old man presented to our department with abdominal discomfort and anorexia and was diagnosed as having Menetrier's disease (MD) with hilar cholangiocarcinoma. Based on his clinical examination, there was no evidence of Helicobacter pylori or cytomegalovirus (CMV) infection. Although we administered proton pump inhibitor and high-calorie enteral nutrition, hypoproteinemia did not improve, and the refractory protein-losing enteropathy persisted. However, interestingly, MD improved immediately after resection of the hilar cholangiocarcinoma. Generally, the etiology of MD is unknown, but H. pylori and CMV infections have been implicated. To our knowledge, there has been no previous report indicating that a malignant tumor could be involved in the etiology of MD. Thus, we report an extremely rare case of MD which is seemingly caused by malignancy. PMID- 27264430 TI - A case of resected hepatocellular carcinoma after drug-eluting bead transarterial chemoembolization. AB - We report a case of resected hepatocellular carcinomas (HCCs) after drug-eluting bead transarterial chemoembolization (DEB-TACE). A 67-year-old man with alcoholic liver disease was diagnosed with HCCs. Serological markers for hepatitis B and C viruses were negative. Among tumor markers, alpha-fetoprotein was 2.7ng/mL, and protein induced by vitamin K absence II was 868mAU/mL. Two HCCs were detected using dynamic computed tomography: one was 9cm in diameter in S8 and the other was 2cm in diameter in S4. We performed DEB-TACE using HepaSphere((r)) and epirubicin. DEB-TACE was repeated three times in three months. Severe postembolization syndrome was not seen with any treatment. Four weeks after the last DEB-TACE, we performed surgical resection. Histopathological study revealed dense distribution of numerous bead particles in necrotic tumor tissue. Otherwise, in non-cancerous tissue, some beads were in portal areas, without necrotic change. Granulomas from foreign body reaction with giant cells were present around the beads. There were no necrotic changes in the smaller HCC, the intrahepatic metastatic nodules, or the microscopic invasion to the portal vein. In conclusion, DEB-TACE would be a useful treatment for huge HCCs; however, patients should be monitored for early recurrence from residual tumor tissue. This study will be helpful to perform DEB-TACE in the future. PMID- 27264431 TI - A case of abdominal tuberculosis lymphadenitis extending into the gallbladder and duodenum in a human T-cell lymphotropic virus type 1 carrier. AB - A 69-year-old man with a history of pulmonary tuberculosis presented with fever. He tested positive for the QuantiFERON TB-2G and human T-cell lymphotropic virus type 1 antibodies. Imaging revealed a mass in the neck of the gallbladder, with periportal lymph node enlargement and penetration into the duodenum. A definite diagnosis could not be made, even with a subsequent detailed examination. Finally, cholecystectomy and a lymph node biopsy were performed. Histopathology revealed a caseating granuloma in the lymph nodes and in the serosa of the gallbladder, and polymerase chain reaction was positive for tuberculosis. Therefore, the patient was diagnosed with abdominal tuberculosis lymphadenitis extending into the gallbladder and duodenum. PMID- 27264432 TI - A case report of gastroduodenal metastasis from skin melanoma. PMID- 27264433 TI - Select membrane proteins modulate MNV-1 infection of macrophages and dendritic cells in a cell type-specific manner. AB - Noroviruses cause gastroenteritis in humans and other animals, are shed in the feces, and spread through the fecal-oral route. Host cellular expression of attachment and entry receptors for noroviruses is thought to be a key determinant of cell tropism and the strict species-specificity. However, to date, only carbohydrates have been identified as attachment receptors for noroviruses. Thus, we investigated whether host cellular proteins play a role during the early steps of norovirus infection. We used murine norovirus (MNV) as a representative norovirus, since MNV grows well in tissue culture and is a frequently used model to study basic aspects of norovirus biology. Virus overlay protein binding assay followed by tandem mass spectrometry analysis was performed in two permissive cell lines, RAW264.7 (murine macrophages) and SRDC (murine dendritic cells) to identify four cellular membrane proteins as candidates. Loss-of-function studies revealed that CD36 and CD44 promoted MNV-1 binding to primary dendritic cells, while CD98 heavy chain (CD98) and transferrin receptor 1 (TfRc) facilitated MNV-1 binding to RAW 264.7 cells. Furthermore, the VP1 protruding domain of MNV-1 interacted directly with the extracellular domains of recombinant murine CD36, CD98 and TfRc by ELISA. Additionally, MNV-1 infection of RAW 264.7 cells was enhanced by soluble rCD98 extracellular domain. These studies demonstrate that multiple membrane proteins can promote efficient MNV-1 infection in a cell type specific manner. Future studies are needed to determine the molecular mechanisms by which each of these proteins affect the MNV-1 infectious cycle. PMID- 27264434 TI - 3-aminopyrazolopyrazine derivatives as spleen tyrosine kinase inhibitors. AB - Spleen tyrosine kinase is a new promising target for drug discovery to treat human cancer and inflammatory disorders. A series of pyrazolopyrazine-3-amine and pyrazolopyrimidine-3-amine derivatives was designed and synthesized as new spleen tyrosine kinase inhibitors. The efforts yielded compound 6h with promising spleen tyrosine kinase inhibition in both enzymatic and B-lymphoma cell proliferation assays. Additionally, compound 6h dose dependently inhibited the activation of spleen tyrosine kinase signal in human B-cell lymphoma cells. Compound 6h might serve as a lead for further development of new spleen tyrosine kinase inhibitors. PMID- 27264435 TI - Serotonin antagonists fail to alter MDMA self-administration in rats. AB - Acute exposure to +/-3,4-methylenedioxymethamphetamine (MDMA) preferentially increases release of serotonin (5-HT), and a role of 5-HT in many of the behavioral effects of acute exposure to MDMA has been demonstrated. A role of 5 HT in MDMA self-administration in rats has not, however, been adequately determined. Therefore, the present study measured the effect of pharmacological manipulation of some 5-HT receptor subtypes on self-administration of MDMA. Rats received extensive experience with self-administered MDMA prior to tests with 5 HT ligands. Doses of the 5-HT1A antagonist, WAY 100635 (0.1-1.0mg/kg), 5-HT1B antagonist, GR 127935 (1.0-3.0mg/kg), and the 5-HT2A antagonist, ketanserin (1.0 3.0mg/kg) that have previously been shown to decrease self-administration of other psychostimulants and that decreased MDMA-produced hyperactivity in the present study did not alter MDMA self-administration. Experimenter-administered injections of MDMA (10.0mg/kg, ip) reinstated extinguished drug-taking behavior, but this also was not decreased by any of the antagonists. In contrast, both WAY 100635 and ketanserin, but not GR 127935, decreased cocaine-produced drug seeking in rats that had been trained to self-administered cocaine. The 5-HT1A agonist, 8 OH-DPAT (0.1-1.0mg/kg), but not the 5-HT1B/1A agonist, RU 24969 (0.3-3.0mg/kg), decreased drug-seeking produced by the reintroduction of a light stimulus that had been paired with self-administered MDMA infusions. These findings suggest a limited role of activation of 5-HT1A, 5-HT1B or 5-HT2 receptor mechanisms in MDMA self-administration or in MDMA-produced drug-seeking following extinction. The data suggest, however, that 5-HT1A agonists inhibit cue-induced drug-seeking following extinction of MDMA self-administration and might, therefore, be useful adjuncts to therapies to limit relapse to MDMA use. PMID- 27264436 TI - Ginkgo biloba and vitamin E ameliorate haloperidol-induced vacuous chewingmovement and brain-derived neurotrophic factor expression in a rat tardive dyskinesia model. AB - Neurodegeneration may be involved in the development of tardive dyskinesia (TD), and low levels of brain-derived neurotrophic factor (BDNF) may play a role. Ginkgo biloba (EGb761), a potent antioxidant, may have neuroprotective effects. We hypothesized that there would be decreased BDNF expression in TD, but that treatment with EGb761 would increase BDNF expression and reduce TD manifestations in a rat model. Forty rats were treated with haloperidol (2mg/kg/day via intraperitoneal injections) for 5weeks. EGb761 (50mg/kg/day) and vitamin E (20mg/kg/day) were then administered by oral gavage for another 5weeks, and we compared the effects of treatment with EGb761 or vitamin E on haloperidol-induced vacuous chewing movements (VCMs) and BDNF expression in four brain regions: prefrontal cortex (PFC), striatum (ST), substantia nigra (SNR), and globus pallidus (GP). Our results showed that haloperidol administration led to a progressive increase in VCMs, but both EGb761 and vitamin E significantly decreased VCMs. Haloperidol also decreased BDNF expression in all four brain regions, but both EGb761 and vitamin E administration significantly increased BDNF expression. Our results showed that both EGb761 and VE treatments exerted similar positive effects in a rat model of TD and increased BDNF expression levels in the four tested brain regions, suggesting that both EGb761 and vitamin E improve TD symptoms, possibly by enhancing BDNF in the brain and/or via their free radical-scavenging actions. PMID- 27264437 TI - A high efficacy cannabinergic ligand (AM4054) used as a discriminative stimulus: Generalization to other adamantyl analogs and Delta(9)-THC in rats. AB - In addition to endogenous lipids, the two main cloned receptors (CB1R and CB2R) of the endocannabinoid signaling system (ECS) can be activated (and blocked) by various exogenous ligands. A relatively novel template for CB1R activators contains an adamantyl moiety as a key structural subunit, the first being the cannabinergic AM411. Additional chemical optimization efforts using the classical tricyclic scaffold led to AM4054. Here we explored the in vivo consequences of novel adamantyl analogs in rats trained to recognize the effects of the potent adamantyl cannabinergic AM4054. Rats were trained to discriminate between AM4054 (0.1mg/kg) and vehicle. Three AM4054 analogs and Delta(9)-THC were tested for generalization (substitution) and antagonism was assessed with rimonabant. We found that all cannabinergics resulted in response generalization to the target stimulus AM4054. The order of potency was: AM4054>=AM4083>=AM4050>AM4089>Delta(9) THC. The CB1R antagonist/inverse agonist rimonabant blocked the discriminative stimulus effects of AM4054. Thus the examined structural modifications affected binding affinities but did not markedly change potencies with the exception of AM4089. In vitro (cAMP assay) functional data have suggested that AM4089 behaves as a partial rather than as a full agonist at CB1R which could explain its lower potency compared to AM4054 (Thakur et al., 2013). The 9beta-formyl functionality at C-9 position was identified as an important pharmacophore yielding high in vivo potency. Antagonism by rimonabant suggested CB1R mediation. PMID- 27264438 TI - Ecology and multilevel selection explain aggression in spider colonies. AB - Progress in sociobiology continues to be hindered by abstract debates over methodology and the relative importance of within-group vs. between-group selection. We need concrete biological examples to ground discussions in empirical data. Recent work argued that the levels of aggression in social spider colonies are explained by group-level adaptation. Here, we examine this conclusion using models that incorporate ecological detail while remaining consistent with kin- and multilevel selection frameworks. We show that although levels of aggression are driven, in part, by between-group selection, incorporating universal within-group competition provides a striking fit to the data that is inconsistent with pure group-level adaptation. Instead, our analyses suggest that aggression is favoured primarily as a selfish strategy to compete for resources, despite causing lower group foraging efficiency or higher risk of group extinction. We argue that sociobiology will benefit from a pluralistic approach and stronger links between ecologically informed models and data. PMID- 27264440 TI - A Concise Review on the Classification and Nomenclature of Stem Cells. AB - Stem cell biology and regenerative medicine is a relatively young field. However, in recent years there has been a tremendous interest in stem cells possibly due to their therapeutic potential in disease states. As a classical definition, a stem cell is an undifferentiated cell that can produce daughter cells that can either remain a stem cell in a process called self-renew!al, or commit to a specific cell type via the initiation of a differentiation pathway leading to the production of mature progeny cells. Despite this acknowledged definition, the classification of stem cells has been a perplexing notion that may often raise misconception even among stem cell biologists. Therefore, the aim of this brief review is to give a conceptual approach to classifying the stem cells beginning from the early morula stage totipotent embryonic stem cells to the unipotent tissue-resident adult stem cells, also called tissue-specific stem cells. PMID- 27264439 TI - Is ascorbate Dr Jekyll or Mr Hyde in the Cu(Abeta) mediated oxidative stress linked to Alzheimer's disease? AB - Evaluation of the pro versus antioxidant activity of ascorbate regarding Cu(Abeta) induced reactive oxygen species production in the context of Alzheimer's disease shows that a protective activity can only be observed at high ascorbate concentration for exogenous molecules but not for the amyloid-beta peptide itself. PMID- 27264441 TI - The evolving treatment paradigm of multiple myeloma: From past to present and future. AB - Multiple myeloma has been recognized since at least the middle of the 19 th century. The list of therapies used in the treat!ment of myeloma is long but only recently has therapeutic success approached a level commensurate with disease con!trol, although cure remains elusive. The complexity of the disease, invidual variations and very active ongoing clinical research warrants continous updating of current information. This review not only summarizes the level of success that has been achieved during the past years but also points to the drawbacks in the current treatment strategies giving emphasize to the potential solutions in the future. PMID- 27264442 TI - Patterns of pancytopenia in Yemen. AB - OBJECTIVE: The aim of this study was to determine the incidence of pancytopenia in relation to sex and age and to become aware of the clinical manifestations of pancytopenic patients according to the causes of pancytopenia. MATERIALS-METHODS: This was a prospective descriptive study that included all patients with pancytopenia admitted to or attending the Hematology-Oncology Department in Al Gamhouria Teaching Hospital, Aden, during the period 1 January-31 December 2005. RESULTS: The most common causes of pancytopenia were malaria and hypersplenism in > 45% of patients, followed by megaloblastic anemia in 14.7%, and aplastic anemia and acute leukemia in 13.3% each. The other causes as determined in the present study were myelodysplasia in 8.0%, myelofibrosis in 4.0% and iron deficiency anemia in 1.3%. The most common symptom was fever in 86.7% of patients. Pallor and splenomegaly were the most common physical findings. CONCLUSIONS: Hypersplenism and malaria were the most common causes of pancytopenia followed by megaloblastic anemia, aplastic anemia and acute leukemia. PMID- 27264443 TI - Lymphomas of Waldeyer's ring: Clinical features, management and prognosis of eleven adult patients. AB - Lymphoma is the second most common neoplasm of the head and neck after squamous carcinoma. The majority of lym!phomas involving the head and neck are non hodgkin's lymphomas. Hodgkin's lymphoma is rare in Waldeyer's ring. Between 1999 and 2006, the medical records and pathology data of all newly diagnosed, previously untreated adult patients with Waldeyer's ring lymphomas were retrospectively reviewed. Pathologic specimens were adopted according to WHO his!tologic classification. All patients were clinically staged with history and physical examination, routine hematologic and bio!chemical profiles, chest X-ray, and computerized tomography of the head and neck, chest, abdomen and pelvis. All patients were treated with chemotherapy. Approximately one month after the end of the scheduled initial management, patients were restaged for evidence of residual disease with physical examination, laboratory profiles and relevant radiologic studies. Total patient number was 11 in our institution. Complete remission was achieved in 6 patients and partial remission in 3 patients; 1 patient did not achieve remission and 1 patient with anaplastic large cell lymphoma died. Patients who are alive are still being followed in our institution. The progression of patients with lymphoma is closely associated with the diagnosis, stage and histologic grade of the disease. This series characterized the clinicopathologic features and outcomes of adult patients. Our data have shown that there is relatively good survival in these diseases but more patients must be evaluated for mean!ingful results. PMID- 27264444 TI - Treatment of thalassemia-induced osteoporosis with intermittent pamidronate infusions: Two-year follow up. AB - OBJECTIVE: The purpose of this study was to evaluate the bone mineral density (BMD) in 23 patients aged 7-14 years with thalassemia major and to assess the alterations in bone density in a two-year follow-up study. METHOD: BMD of the lumbar spine and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) at baseline, after 12 months of treatment and two years later. Pamidronate treatment (15 mg/dose, every 3 months for 1 year) was given to 23 osteoporotic (Z score below -2.5) and osteopenic (Z score -1 to -2.5) patients. After 12 months of treatment, all patients received only calcium and vitamin D supplements. After the two years of follow-up, BMD of the lumbar spine and femur was measured using DXA. RESULT: Administration of pamidronate resulted in a significant increase in BMD of the femoral neck. Lumbar spine BMD after pamidronate treatment was slightly higher than at baseline, but this was statistically non-significant. After two years, femoral neck and lumbar BMD had significantly increased compared to baseline. CONCLUSION: In view of the present findings, longer follow-up studies to determine long-term treatment are fully warranted. PMID- 27264445 TI - Aspirin resistance frequency in healthy males. AB - INTRODUCTION: Aspirin has been shown to have variable antiplatelet activity in individuals. Previous studies have estimated that 5% to 45% of the population do not achieve an adequate antiplatelet effect from aspirin and still suffer ischemic events despite therapy. AIM: In this study, we aimed to evaluate aspirin resistance in healthy males. METHOD: We prospectively enrolled 175 healthy males who were >=19 years old and taking 100 mg of aspirin daily >=7 consec!utive days before study entry. Demographic information and laboratory data were collected. Aspirin resistance was detected by optical platelet aggregometry, a widely accepted method using adenosine diphosphate (ADP) and arachidonic acid (AA). RESULT: 28% of the participants were aspirin-resistant, 62% were aspirin-semi responders and 10% were aspirin-sensitive. The aspirin-resistant individuals were older than the semi-responders (p<0.01), and had higher erythrocyte sedimentation rate than the semi-responders (p<0.01) and sensitive individuals (p<0.05). CONCLUSION: Our study demonstrates aspirin resistance to be particularly important given its high frequency in our study population. The biological effects of aspirin, which is widely used as an antithrombotic drug, are not similar in all individuals. PMID- 27264446 TI - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloblastic leukemia (AML): A single center experience. AB - OBJECTIVE: We retrospectively analyzed the impact of pre- and post-transplant variables on the outcome of transplanta!tion in 145 consecutive patients with acute myeloblastic leukemia (AML) allografted from their HLA-identical siblings in our single center cohort. RESULTS: The stem cell source used was bone marrow (BM) (36.6%) or peripheral blood (PB) (63.4%). Both neutrophil and platelet engraftments were observed on the median 14th day. Engraftment was faster in the PB group than in the BM group (p<0.0001). Severe acute graft versus host disease (aGvHD) was observed in 27.9% of the patients while chronic (c)GvHD developed in 61.2%. The use of PB was associated with more severe aGvHD. Estimated leukemia free survival (LFS) and overall survival (OS) at 10 years were 43.4%+/-5.2% and 52.7%+/-4.6%, respectively. CONCLUSION: Both in univariate and multivariate analyses for LFS and OS, remission status at transplant and the presence of aGvHD were independent risk factors. PMID- 27264447 TI - Clonal evolution of monosomy 7 in acquired severe aplastic anemia: Two cases treated with allogeneic hematopoietic stem cell transplantation. AB - Aplastic anemia (AA) may evolve into clonal diseases like myelodysplastic syndrome (MDS) and acute myeloblastic leuke!mia (AML). Monosomy 7 is a poor prognostic chromosomal abnormality commonly associated with therapy related MDS and secondary AML. It has also been associated with leukomogenic transformation in AA. We present here two adult ma!le patients with acquired severe AA. Both patients had received immunosuppressive therapy (IST) as first line treatment and had monosomy 7 positive clone at transformation to MDS with refractory anemia and excess of blast (RAEB-II) and AML, respectively. Both patients have undergone allogeneic hematopoietic stem cell (HSC) transplantation from their HLA identical donors (unrelated and sibling). PMID- 27264448 TI - A patient with extramedullary acute myeloid leukaemia involving the brachial plexus: Case report and review of the literature. AB - Extramedullary leukaemic involvement is not uncommon as part of the presentation in acute myeloid leukaemia (AML). However, infiltrative peripheral neuropathy due to AML was rarely reported. We report a case of extramedullary leukaemic infiltration of the brachial plexus in a patient with relapsed AML. PMID- 27264449 TI - Diffuse alveolar hemorrhage due to donor lymphocyte infusion in a case of acute lymphoblastic leukemia. AB - Diffuse alveolar hemorrhage, with a mortality rate between 60-100%, is a life threatening complication in hematopoietic stem cell transplant recipients. A 34 year-old man, with precursor B acute lymphoblastic leukemia diagnosed in July 2003, relapsed after allogeneic peripheral blood hematopoietic stem cell transplantation from his human leukocyte antigen- iden!tical brother in July 2005. He received a donor lymphocyte infusion of 2 x 107/kg CD3 positive cells. He developed fever, dyspnea and hypoxemia four days after donor lymphocyte infusion. The patient was diagnosed as diffuse alveolar hem!orrhage based on the clinical, radiological and bronchoscopic data. He was immediately started on high dose methylpred!nisolone. Two days after the onset of the steroid therapy, he recovered with significant improvement in oxygenation. Diffuse alveolar hemorrhage can be a late-onset transplant complication that could also be associated with a recent donor lymphocyte infusion. PMID- 27264450 TI - Development of zona zoster during bortezomib treatment in patients with Relapsed/Refractory multiple myeloma. PMID- 27264451 TI - Idiopathic thrombocytopenic purpura (ITP) in childhood. PMID- 27264452 TI - The correlation between soluble endothelial protein c receptor (sEPCR) and tumor necrosis factor-alpha (TNF-alpha) levels in vivo. PMID- 27264453 TI - The bone marrow in hereditary cystinosis. PMID- 27264454 TI - A SMART design to optimize treatment strategies for patient and family caregiver outcomes. AB - Sequential multiple randomization trial (SMART) designs are experimental designs used to identify treatment strategies that maximize targeted health outcomes. SMART designs are receiving greater attention in nursing and other health disciplines to develop multicomponent interventions that are tailored to the patient's (or family caregiver's) needs and preferences. A SMART design resembles a traditional randomized controlled trial (RCT) design in that it scientifically examines intervention effects with randomization. However, the two designs address very different research inquiries. In this article, we compare traditional RCT designs and SMART designs, describe the adaptive treatment framework that underlies SMART designs and key features of SMART designs, and illustrate the application of a SMART design to develop an adaptive palliative care treatment to improve patient and caregiver outcomes. PMID- 27264455 TI - CD4(+) T cells in patients with chronic inflammatory rheumatic disorders show distinct levels of exhaustion. PMID- 27264456 TI - Differences in human gingival and dermal fibroblasts may contribute to oral induced tolerance against nickel. PMID- 27264457 TI - IgG and IgG4 to 91 allergenic molecules in early childhood by route of exposure and current and future IgE sensitization: Results from the Multicentre Allergy Study birth cohort. AB - BACKGROUND: Studies of a limited number of allergens suggested that nonsensitized children produce IgG responses mainly to foodborne allergens, whereas IgE sensitized children also produce strong IgG responses to the respective airborne molecules. OBJECTIVE: We sought to systematically test the hypothesis that both the route of exposure and IgE sensitization affect IgG responses to a broad array of allergenic molecules in early childhood. METHODS: We examined sera of 148 children participating in the Multicentre Allergy Study, a birth cohort born in 1990. IgG to 91 molecules of 42 sources were tested with the ImmunoCAP Solid Phase Allergen Chip (ISAC; TFS, Uppsala, Sweden). IgE sensitization at age 2 and 7 years was defined by IgE levels of 0.35 kUA/L or greater to 1 or more of 8 or 9 extracts from common allergenic sources, respectively. RESULTS: The prevalence and geometric mean levels of IgG to allergenic molecules in nonsensitized children were lower at age 2 years than in IgE-sensitized children, and they were extremely heterogeneous: highest for animal food (87% +/- 13%; 61 ISAC Standardized Units [ISU], [95% CI, 52.5-71.5 ISU]), intermediate for vegetable food (48% +/- 27%; 13 ISU [95% CI, 11.2-16.1 ISU]), and lowest for airborne allergens (24% +/- 20%; 3 ISU [95% CI, 2.4-3.4 ISU]; P for trend < .001 [for percentages], P for trend < .001 [for levels]). IgG4 antibodies were infrequent (<5%) and contributed poorly (<3%) to overall IgG antibody levels. IgG responses at age 2 years were slightly more frequent and stronger among children with than in those without IgE sensitization at age 7 years. CONCLUSION: The children's repertoire of IgG antibodies at 2 years of age to a broad array of animal foodborne, vegetable foodborne, and airborne allergenic molecules is profoundly dependent on the route of allergen exposure and the child's IgE sensitization status and only marginally involves the IgG4 isotype. PMID- 27264458 TI - A combination of dexamethasone and anti-IL-17A treatment can alleviate diesel exhaust particle-induced steroid insensitive asthma. PMID- 27264459 TI - Evaluating the ability of artificial neural network and PCA-M5P models in predicting leachate COD load in landfills. AB - Waste burial in uncontrolled landfills can cause serious environmental damages and unpleasant consequences. Leachates produced in landfills have the potential to contaminate soil and groundwater resources. Leachate management is one of the major issues with respect to landfills environmental impacts. Improper design of landfills can lead to leachate spread in the environment, and hence, engineered landfills are required to have leachate monitoring programs. The high cost of such programs may be greatly reduced and cost efficiency of the program may be optimized if one can predict leachate contamination level and foresee management and treatment strategies. The aim of this study is to develop two expert systems consisting of Artificial Neural Network (ANN) and Principal Component Analysis M5P (PCA-M5P) models to predict Chemical Oxygen Demand (COD) load in leachates produced in lab-scale landfills. Measured data from three landfill lysimeters, including rainfall depth, number of days after waste deposition, thickness of top and bottom Compacted Clay Liners (CCLs), and thickness of top cover over the lysimeter, were utilized to develop, train, validate, and test the expert systems and predict the leachate COD load. Statistical analysis of the prediction results showed that both models possess good prediction ability with a slight superiority for ANN over PCA-M5P. Based on test datasets, the mean absolute percentage error for ANN and PCA-M5P models were 4% and 12%, respectively, and the correlation coefficient for both models was greater than 0.98. Developed models may be used as a rough estimate for leachate COD load prediction in primary landfill designs, where the effect of a top and/or bottom liner is disputed. PMID- 27264461 TI - Removal of Bisphenol A aqueous solution using surfactant-modified natural zeolite: Taguchi's experimental design, adsorption kinetic, equilibrium and thermodynamic study. AB - In this study, surfactant-modified natural zeolite was used to remove Bisphenol A (BPA) from aqueous solutions. Kinetics, equilibrium and thermodynamics of BPA adsorption on the adsorbent surfaces were investigated. The experimental data were described with the Temkin isotherm and the pseudo-second- order kinetic model. Taguchi's robust design approach was used to optimize adsorption of BPA. Experimentation was planned as per Taguchi's L27 orthogonal array. Tests were conducted with different adsorbate amount, pH, time, initial concentration of BPA, temperature and agitation speed. The optimum levels of control factors for maximum total organic carbon removal were defined (adsorbate amount at 0.25 g, pH at 7, time at 30 min, initial concentration of BPA at 50 mg/L, temperature at 30 degrees C and agitation speed at 200 rpm). The ANOVA analysis shown that the most effective control factor is adsorbent dosage; its contribution is 56.4%. Contribution of pH and mixing rate are 7.5% and 7.6%, respectively. A confirmation experiment was conducted to verify the feasibility and effectiveness of the optimal combination. The observed value of S/N (etaobs = 39) ratio is compared with that of the predicted value (etaopt = 48). The prediction error, that is, etaopt - etaobs = 9, is within CI value. PMID- 27264460 TI - Enhancement of simultaneous gold and copper recovery from discarded mobile phone PCBs using Bacillus megaterium: RSM based optimization of effective factors and evaluation of their interactions. AB - Bioleaching of Au from mobile phone printed circuit boards (MPPCBs) was studied, using Bacillus megaterium which is a cyanogenic bacterium. To maximize Au extraction, initial pH, pulp density, and glycine concentration were optimized via response surface methodology (RSM). Bioleaching of Cu, an important inhibitor on Au recovery, was also examined. To maximize Au recovery, the optimal condition suggested by the models was initial pH of 10, pulp density of 8.13g/l, and glycine concentration of 10g/l. Under the optimal condition, approximately 72% of Cu and 65g Au/ton MPPCBs, which is 7 times greater than the recovery from gold mines, was extracted. Cu elimination from the MPPCBs having a rich content of Au did not cause a significant effect on Au recovery. It was found that when the ratio of Cu to Au is high, Cu elimination can considerably improve Au recovery. B. megaterium could extract the total Au from PCBs containing 130g Au/ton MPPCBs. PMID- 27264462 TI - Effects of Desialylation on Chemoattractant Induced Chemotaxis. AB - The amount of sialic acid on the surface of the neutrophil influences its ability to interact with other cells. Neutrophil activation with various stimuli mobilizes intracellular sialidase to the plasma membrane where it cleaves sialic acid from cell surfaces. Since enhanced neutrophil adherence, spreading, deformability and motility each are associated with surface desialylation and critical to neutrophil diapedesis, we studied the role of sialic acid on neutrophil chemotaxis with interleukin-8 (IL-8), leukotriene B4 (LTB4), fMet-Leu Phe (fMLP) and complement 5a in vitro. Migration of NANase-treated neutrophil across 3 MU pore size polycarbonate membranes was decreased in response to IL-8 and LTB4 but not to fMLP and complement 5a. These findings suggest that sialic acid content of receptors have a key role on chemoattractant-receptor binding and may be a novel strategy for limiting the inflammatory response. PMID- 27264463 TI - Beta-Thalassemia Mutations in the East of Turkey. AB - This study was planned to determine the frequency of beta-thalassemia trait and mutations in Van Lake region, which is in the eastern part of Turkey, surrounded by Iran in the east and by Iraq in the south. This study consist of 1014 healthy students, between the age of 12 and 18 years who are studying in boarding schools in Van city and cities surrounding Van Lake that includes Van, Agri, Hakkari, Bitlis, Mus and Siirt. The students were randomly selected according to their school numbers. Their origin was not taken into consideration in selection. Complete blood counts were performed on all donors. The accepted lower limit of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were 78 fL and 27 pg respectively. HbA2 was measured by DE-52 microcolumn chromatography method. beta-thalassemia trait with high HbA2 was found in 6 children. beta thalassemia homozygous form of -30 (T-A) mutation was determined in one child and HbD-Los Angeles heterozygous in another. The beta-thalassemia homozygous individual was accepted as two cases in prevalence calculation. We found that the prevalence of beta-thalassemia trait was 0.78% in this area. In DNA analyses, there were beta-thalassemia gene mutations of FSC 8/9 (+G), -30 (T-A), IVS I-110 (G-A), IVS II-1 (G-A) and IVS I-130 (G-A) in 3, 2, 1, 1 and 1 individuals, respectively. We conclude that although five different beta-thalassemia mutation exist in Van Lake region, beta-thalassemia is not a potential risk in the east of Turkey. PMID- 27264464 TI - Frequency of FV 1299 His-Arg (A4070G) in Turkish Cypriots. AB - FV 1299 His-Arg polymorphism was recently determined to be common in Turkish population (8.5%). This polymorphism contribute to the activated protein C resistance phenotype. We aimed to examine the frequency of this polymorphism in Turkish Cypriots. PMID- 27264465 TI - Platelet Functions in Patients with Allergic Asthma. AB - To investigate platelet functions in patients suffering from allergic diseases including asthma, blood was collected from ten asthmatic patients (five females, five males) and ten healthy controls (five females, five males) and by using whole-blood electrical impedance system; platelet count and platelet aggregation studies (maximum aggregation extent, maximum aggregation rate) were performed. Allergy screening was performed with skin test reactions and with high total and specific immunoglobulin E levels (CAP-Phadiatop system). Platelet count (333.1 +/ 41.1 x 109/L), collagen induced the response of platelet aggregation (12.95 +/- 4.19) and maximum rate of aggregation (8.00 +/- 5.22) in allergic patients were found significantly higher than those of controls (252.1 +/- 49.1 x 109/L; 8.33 +/- 1.19; 4.28 +/- 1.31) (p< 0.05). Also ADP induced response of platelet aggregation (18.21 +/- 3.56) and maximum rate of aggregation (10.64 +/- 2.12) in asthmatic patients were higher than controls (12.37 +/- 2.63; 7.80 +/- 1.64) with statistical significance (p< 0.01). Secretion products of activated platelets such as histamine, serotonin, PGF2alpha and PAF may play role in bronchial responsiveness in allergic asthma. The results of this study showed that platelet function tests were effected in asthmatic patients. The changes in platelet functions are thought to be related with increased IgE levels and stimulation of platelets by these antibodies. PMID- 27264466 TI - Effect of Sialic Acid on Platelet Cryopreservation. AB - Sialic acid is a molecule which is responsible for the net negative surface charge of platelets. We investigated the effect of sialic acid on fresh and cryopreserved platelets. Platelet samples were obtained by platelet apheresis from 8 healthy donors. Platelet suspensions with different sialic acid concentrations (0, 1, 2 and 4 mg/mL) were studied for ADP and ristocetin induced platelet aggregation, basal and ADP induced P-selectin and glycoprotein- Ib/IX expression. Then platelet samples were cryopreserved in 5% DMSO with or without 4 mg/mL sialic acid. After thawing, P-selectin expression was compared with the control group. Six samples were also washed after thawing and P-selectin expression was again compared to unwashed samples. Sialic acid suppressed ADP induced platelet aggregation and P-selectin expression in a dose dependent manner. In cryopreserved samples, P-selectin expression of 4 mg/mL sialic acid containing group was found significantly higher than the control group (p< 0.001). In cryopreserved control group, P-selectin expression of thawedwashed group was significantly higher than thawed-unwashed group (p< 0.05). Our results indicate that sialic acid is not a good cryoprotective agent. Washing procedure after thawing to eliminate DMSO causes significant platelet activation. PMID- 27264467 TI - Thrombosis After Splenectomy in Patients with Thalassemia. AB - Thrombosis is one of the most important complications after splenectomy and requires fast diagnosis, effective therapy and good follow-up. The aim of this study is to investigate the effects of thrombocytosis and natural inhibitors on thrombosis after splenectomy. We detected thrombosis in the portal vein system in 7 of the 30 splenectomized patients (23.3%) by Doppler Colour Flow Imaging. There was no statistical increase of thrombocyte count in patients with or without thrombosis. Natural inhibitor levels in all patients were lower than controls (p< 0.001), but there was not any statistical difference between the patients with and without thrombosis. PMID- 27264468 TI - Histopathologic and Immunophenotypic Features of Childhood and Adult Anaplastic Large-Cell Lymphomas. AB - The t (2;5) (p23; q35) translocation associated with CD30-positive anaplastic large-cell lymphoma (ALCL) creates a hybrid gene encoding the chimeric nucleolar protein nucleophosmin-anaplastic lymphoma kinase (NFMALK) protein, which can be demonstrated by immunostaining with ALK1 monoclonal antibody. In this study, 40 specimens of ALCL from 6 pediatric, 34 adult patients, were immunostained with monoclonal antibodies against CD30 (Ber-H2), EMA, CD45 (LCA), CD3, CD20 (L26), CD15, and ALK1 antigens, and results were correlated with histopathologic features. The mean age of the pediatric and adult patients was 10-years and 38 years, respectively. ALK1 was positive in 14 cases (35%) representing 83% of pediatric and 26% of adult patients, statistically significantly higher in the pediatric group (p= 0.01). Considering the better prognosis attributed to cases with t (2;5), it is interesting to note that the percentage of ALK1-positive cases is significantly higher in pediatric patients with coexpression of EMA, compared to adults. PMID- 27264469 TI - Plasma Cell Leukemia: A Report of 5 Cases and Review of the Literature. AB - Plasma cells are occasionally observed in the peripheral blood of the patients with multiple myeloma. When the number of these circulating cells is significant, the term of plasma cell leukemia is used. We report 5 cases of plasma cell leukemia with poor prognosis with review of the literature. PMID- 27264470 TI - A Case with Gaucher-Like Cells. AB - Gaucher-like cells (GLC) are sometimes indistinguishable from real Gaucher cells. GLC can be detected in various diseases. We present a 4.5 year old boy with massive cervical lympadenopathy and an intraabdominal mass mimicking lymphoma. Many GLC were seen in the fine needle aspiration material of an enlarged lymph node. Ziehl-Neelsen stain of the aspirate revealed many acid-fast bacteria in the GLC. Fine needle aspiration might provide valuable information in the evaluation of enlarged lymph nodes. PMID- 27264472 TI - Images in Haematology. PMID- 27264471 TI - Unusual Cause of Back Pain in a Multiple Myeloma Patient: Infectious Discitis. AB - A 58 year old patient, followed up for diabetes mellitus and multiple myeloma for ten years and six months, respectively, presented with persistent back pain, weakness at his lower extremity and intermittent fever. Activation markers of myeloma were in normal limits except high erythrocyte sedimentation rate and elevated C-reactive protein. Magnetic resonance imaging revealed increased T1 spinal intensity at the suspected disc level. Discitis was suspected on the basis of MRl and high fever. An intraoperative examination of specimens revealed Staphylococcus aureus. Detailed laboratory and radiological investigations should be performed to diagnose unusual causes of persistent back pain, such as discitis in patients with myeloma. PMID- 27264473 TI - Prevalence of Hemoglobinopathies in Denizli and Kahramanmaras. PMID- 27264474 TI - Efficiency and stability of spectral sensitization of boron-doped-diamond electrodes through covalent anchoring of a donor-acceptor organic chromophore (P1). AB - A novel procedure is developed for chemical modification of H-terminated B-doped diamond surfaces with a donor-pi-bridge-acceptor molecule (P1). A cathodic photocurrent near 1 MUA cm(-2) flows under 1 Sun (AM 1.5) illumination at the interface between the diamond electrode and aqueous electrolyte solution containing dimethylviologen (electron mediator). The efficiency of this new electrode outperforms that of the non-covalently modified diamond with the same dye. The found external quantum efficiency of the P1-sensitized diamond is not far from that of the flat titania electrode sensitized by a standard organometallic dye used in solar cells. However, the P1 dye, both pure and diamond-anchored, shows significant instability during illumination by solar light. The degradation is a two-stage process in which the initially photo generated products further decompose in complicated dark reactions. These findings need to be taken into account for optimization of organic chromophores for solar cells in general. PMID- 27264476 TI - Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases. AB - BACKGROUND AND OBJECTIVES: While the prognostic role of KRAS status after resection of CRLM has been previously explored, the importance of KRAS status relative to the receipt of preoperative chemotherapy remains largely unknown. METHODS: A total of 430 patients who underwent curative-intent surgery for CRLM between 2000 and 2015 and who had available KRAS genotype data were identified. Data regarding KRAS mutation status, receipt of preoperative chemotherapy, and overall survival (OS) were assessed using univariable and multivariable analyses. RESULTS: Median patient age was 58 years (IQR, 50.4-66.4 years). A total of 258 patients (60.0%) received preoperative chemotherapy, while 172 (40.0%) had upfront surgery. Median and 5-year OS in the entire cohort was 65.1 months and 53.2%, respectively. KRAS mutation was associated with a worse 5-year OS compared with wild-type tumors (HR 1.41; P = 0.042). After stratifying by the receipt of preoperative chemotherapy, the prognostic value of KRAS mutation only persisted among patients who had received preoperative chemotherapy (HR 1.67; P = 0.012). In contrast, KRAS mutation status had no impact on OS among patients who had not received preoperative chemotherapy (P = 0.597). CONCLUSIONS: KRAS mutation status was an independent predictor of OS among patients undergoing liver resection of CRLM. However, after stratifying by receipt of preoperative chemotherapy, KRAS was informative relative to prognosis only among patients who received preoperative chemotherapy. J. Surg. Oncol. 2016;114:361-367. (c) 2016 Wiley Periodicals, Inc. PMID- 27264477 TI - Two-dimensional TaC nanosheets on a reduced graphene oxide hybrid as an efficient and stable electrocatalyst for water splitting. AB - A novel highly active and stable HER catalyst containing two-dimensional TaC nanosheets hybridized with reduced graphene oxide (2D TaC-RGO) was prepared as an efficient and stable hydrogen evolution reaction catalyst. PMID- 27264475 TI - Early severe institutional deprivation is associated with a persistent variant of adult attention-deficit/hyperactivity disorder: clinical presentation, developmental continuities and life circumstances in the English and Romanian Adoptees study. AB - BACKGROUND: Early-life institutional deprivation is associated with attention deficit/hyperactivity disorder (ADHD) later in childhood and adolescence. In this article, we examine, for the first time, the persistence of deprivation-related ADHD into young adulthood in a sample of individuals adopted as young children by UK families after periods in extremely depriving Romanian orphanages. METHODS: We estimated rates of ADHD at age 15 years and in young adulthood (ages 22-25 years) in individuals at low (LoDep; nondeprived UK adoptees and Romanian adoptees with less than 6-month institutional exposure) and high deprivation-related risk (HiDep; Romanian adoptees with more than 6-month exposure). Estimates were based on parent report using DSM-5 childhood symptom and impairment criteria. At age 15, data were available for 108 LoDep and 86 HiDep cases, while in young adulthood, the numbers were 83 and 60, respectively. Data on education and employment status, IQ, co-occurring symptoms of young adult disinhibited social engagement (DSE), autism spectrum disorder (ASD), cognitive impairment, conduct disorder (CD), callous-unemotional (CU) traits, anxiety, depression and quality of life (QoL) were also collected. RESULTS: ADHD rates in the LoDep group were similar to the general population in adolescence (5.6%) and adulthood (3.8%). HiDep individuals were, respectively, nearly four (19%) and over seven (29.3%) times more likely to meet criteria, than LoDep. Nine 'onset' young adult cases emerged, but these had a prior childhood history of elevated ADHD behaviours at ages 6, 11 and 15 years. Young adult ADHD was equally common in males and females, was predominantly inattentive in presentation and co-occurred with high levels of ASD, DSE and CU features. ADHD was associated with high unemployment and low educational attainment. CONCLUSION: We provide the first evidence of a strong persistence into adulthood of a distinctively complex and impairing deprivation-related variant of ADHD. Our results confirm the powerful association of early experience with later development in a way that suggests a role for deep seated alterations to brain structure and function. PMID- 27264478 TI - Effect of fetal gender on pregnancy outcomes in Northern China. AB - PURPOSE: Several studies have demonstrated that fetal gender has a significant effect on the pregnancy outcomes and pregnancy-related complications. However, results differ as the race and population changes. The aim of our study was to test whether the recorded phenomenon of adverse pregnancy outcomes associated with a male fetus applies to women in northern China. METHODS: This was a multi centered, cross-sectional study. The study population included women who delivered babies in 25 different hospitals in 9 provinces in northern China, from 1 January 2011 to 31 December 2011. For our analysis, we selected 65 173 singleton birth deliveries at or after 28 weeks that occurred during the year 2011. RESULTS: Male fetal gender was associated with an increased incidence of preterm delivery (8.33% for males; 7.19% for females), gestational diabetes mellitus (4.58% for males; 4.26% for females), fetal macrosomia (9.41% versus 5.78%), lower Apgar score (2.05% versus 1.78%), perinatal death (0.92% versus 0.76%), placenta previa (0.95% versus 0.81%), increased cesarean section delivery (54.87% versus 52.31%) and operative delivery (1.34% versus 1.19%) (p < 0.05). However, female fetuses were associated with an increased risk of preeclampsia at an advanced gestational age (15.86% for males; 17.53% for females), fetal growth restriction (0.74% for males; 1.09% for females), malpresentation (3.6% for males; 4.31% for females), postpartum hemorrhage (2.92% for males; 3.19% for females) (p < 0.05). CONCLUSIONS: The recorded phenomenon of adverse pregnancy outcomes associated with a male fetus applies to our population regardless of some different results. PMID- 27264484 TI - The utility of thromboelastography in inherited and acquired bleeding disorders. AB - Thromboelastography (TEG) was first described by Hartert in 1948, and was designed to monitor viscoelastic clot strength in whole blood in real time. The current TEG method and Rotational Thromboelastometry (ROTEM) were subsequently developed from the original principles. Both of the modern methods provide data by measuring changes in the viscoelastic strength of a small sample of clotting blood in response to a constant rotational force. The important advantage of these techniques is to visually observe and quantify blood coagulation including the propagation, stabilization and dissolution phases of clot formation under low shear conditions. Analysis of the results provides detailed kinetic data on fibrin generation, clot strength and fibrinolysis. These TEG/ROTEM analyses therefore enable evaluation of global clotting function and the monitoring of haemostatic treatment in various clinical situations, not only in patients with genetic bleeding disorders, such as haemophilia, but also in patients undergoing cardiac surgery, liver transplantation or suffering from traumatic injury. Some evidence suggests that haemostatic management using TEG/ROTEM leads to a reduction in total transfusions of whole blood or clotting factors. Wider clinical application of this technology seems likely. PMID- 27264483 TI - miR-21-5p renal expression is associated with fibrosis and renal survival in patients with IgA nephropathy. AB - IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN. In the context of IgAN, we aimed to analyze the role of miR-21-5p, miR-214-3p and miR-199a-5p, three established "fibromiRs" involved in renal fibrosis. Fifty-six IgAN biopsy specimens were retrospectively scored according to Oxford classification. Renal expression of miR-21-5p, miR-214-3p and miR-199a-5p were significantly associated with T score (miR-21-5p T0 RQ median = 1.23, T1 RQ = 3.01, T2 RQ = 3.90; miR-214-5p T0 RQ = 1.39, T1 RQ = 2.20, T2 RQ = 2.48; miR-199a-5p T0 RQ = 0.76, T1 RQ = 1.41, T2 RQ = 1.87). miR-21-5p expression was associated with S score (S0 RQ median = 1.31, S1 RQ = 2.65), but not miR-214 3p nor miR-199a-5p. In our cohort, poor renal survival was associated with high blood pressure, proteinuria and elevated creatininemia, as well as T and S scores. Moreover, renal expression of miR-21-5p, miR-214-3p were associated with renal survival. In conclusion, miR-21-5p, miR-214-3p and miR-199a-5p are three "fibromiRs" involved in renal fibrosis in the course of IgAN and miR-21-5p and miR-214-3p are associated with renal survival. PMID- 27264485 TI - Food consumption and activity levels increase in rats following intranasal Hypocretin-1. AB - Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery. Food intake and wheel-running activity were quantified for 24h after IN delivery. Biodistribution was determined 30min after IN delivery of both a high and low dose of 125I-radiolabelled HC throughout the brain and other bodily tissues, while Western blots were used to quantify changes in cell signaling pathways (MAPK and PDK1) in the brain. Intranasal HC significantly increased food intake and wheel activity within 4h after delivery, but balanced out over the course of 24h. The distribution studies showed dose-dependent delivery in the CNS and peripheral tissues, while PDK1 was significantly increased in the brain 30min after IN delivery of HC. This study adds to the growing body of evidence that IN administration of HC is a promising strategy for treatment of HC related behaviors. PMID- 27264486 TI - Altered economic decision-making in abstinent heroin addicts: Evidence from the ultimatum game. AB - BACKGROUND: The development and persistence of drug addiction has been suggested to involve decision-making deficits. The Ultimatum Game is a widely used economic decision-making paradigm that illustrates the tension between financial self interest and fairness motives. The behavior of responders in the Ultimatum Game has been associated with emotional reactions and cognitive control abilities, both of which are dysregulated in drug addicts. In this study, we investigated whether this economic decision-making process that involves considerations of social norms is affected by heroin addiction. METHODS: Heroin addicts (n=17) and demographically matched healthy control subjects (n=18) were recruited to play the part of responders in the Ultimatum Game, during which they decided to accept or reject the monetary offers proposed by strangers. The offers were manipulated by varying the stake sizes and fairness scales. The rejection rates of all of the offer categories, response times, fairness judgments, and impulsivity were compared between heroin addicts and healthy controls. RESULTS: Compared with healthy subjects, the rejection rates of most unfair offers in the Ultimatum Game were significantly higher under low-offer-size conditions among heroin addicts. In contrast, the most unfair offers were more likely to be accepted by heroin addicts in the high-offer-size condition than by healthy subjects. The ratings of unfairness were equal in both conditions although the rejection rates were different. Heroin addicts had higher scores on BIS attentional/cognitive impulsivity and non-planning impulsivity, but not in motor impulsivity. Rejection rates to most unfair offers under low-offer-size conditions significantly correlated with score on BIS non-planning impulsivity and total score of impulsivity. CONCLUSIONS: Heroin addicts differentially responded under different stake-level conditions in the Ultimatum Game, with emotional impulses in low offer-size conditions and selfish motives in the face of high monetary reward. These findings indicate that Ultimatum Game may be associated with heroin addiction and provide a productive new target for enhancing treatment for heroin addiction. PMID- 27264487 TI - A microarray study of chronic unpredictable mild stress rat blood serum with electro-acupuncture intervention. AB - In the present study, we investigated the changes of microRNA (miRNA) expression upon depression and electro-acupuncture (EA) intervention in chronic unpredictable mild stress (CUMS) rats using microarray analysis. Results showed that EA intervention remarkably improved behavioral indexes in terms of crossing number, rearing number, sucrose preference and body weight of CUMS rats. Microarray analysis revealed that a total of 153 differentially expressed miRNAs were regulated by CUMS, and the expression of 180 differentially expressed miRNAs was changed after EA intervention. Among these miRNAs, two miRNAs were significantly up-regulated and four miRNAs were significantly down-regulated by CUMS. Moreover, four miRNAs were significantly up-regulated and 12 miRNAs were significantly down-regulated after EA intervention. The expressions of miR-383-5p and miR-764-5p were up-regulated after CUMS, while their expressions were down regulated by EA intervention. Further analysis showed that 1260 possible target genes were predicted for miR-383-5p and miR-764-5p, and 97 pathways and 137 gene ontology (GO) were involved. Among these pathways and GO, about 20 pathways and 21 GO were related to depression. Changes of miR-383-5p and miR-764-5p indicated that EA might exert its therapeutic effect on depression through promoting the neurotrophy and inhibiting the abnormal apoptosis of neurons as well as other correlative signal pathways. In conclusion, our present study enriched the understanding of pathological process of depression and revealed possible mechanisms of EA on depression. PMID- 27264488 TI - Neprilysin: Indications, Expectations, and Challenges. PMID- 27264489 TI - Minimally Invasive Approach for Valvular Surgery and Atrial Septal Defect. PMID- 27264490 TI - Clinical Outcomes After Implantation of Overlapping Bioresorbable Scaffolds vs New Generation Everolimus Eluting Stents. AB - INTRODUCTION AND OBJECTIVES: There is limited evidence on procedural and clinical outcomes in patients treated with overlapping bioresorbable scaffolds vs overlapping everolimus-eluting stents. We evaluated the outcomes of propensity matched patients treated with overlapping scaffolds vs everolimus-eluting stents. METHODS: After propensity matching, 70 consecutive stable angina patients treated with overlapping bioresorbable scaffolds and 70 patients treated with overlapping new generation everolimus stents were included in this study. The primary outcome was the 1-year rate of major adverse cardiovascular events, defined as the composite of all-cause mortality, nonprocedural myocardial infarction, and target vessel revascularization. RESULTS: Patients in the 2 groups had similar age (scaffold vs stent: 64.5 +/- 10.3 vs 66 +/- 9.7 years; P=.381), sex, diabetes, previous cardiovascular history, and SYNTAX score (scaffold vs stent: 18.6 +/- 9.2 vs 19.4 +/- 10.4; P=.635). Postprocedural acute gain was significantly lower in patients treated with scaffolds (1.82+/-0.66 vs 2.03+/-0.68mm; P=.033). At 1 year follow up, the estimated major adverse cardiovascular event rate was not significantly different between the 2 groups (scaffold vs stent: 14.5% vs 14.6%; Plog-rank=.661). Similarly, no significant differences were seen in 1-year rates of target vessel (scaffold vs stent: 14.5% vs 10%; Plog-rank=.816) or target lesion revascularization (scaffold vs stent: 9.7% vs 8.3%; Plog-rank=.815). CONCLUSIONS: Treating long lesions with overlapping scaffolds is feasible with acceptable 1-year outcomes. PMID- 27264491 TI - Correction of Congenital Cardiac Defects With CorMatrix Extracellular Matrix in Pediatric Patients: Is It Really Safe? PMID- 27264492 TI - High-resolution contrast-enhanced optical coherence tomography in mice retinae. AB - Optical coherence tomography (OCT) is a noninvasive interferometric imaging modality providing anatomical information at depths of millimeters and a resolution of micrometers. Conventional OCT images limit our knowledge to anatomical structures alone, without any contrast enhancement. Therefore, here we have, for the first time, optimized an OCT-based contrast-enhanced imaging system for imaging single cells and blood vessels in vivo inside the living mouse retina at subnanomolar sensitivity. We used bioconjugated gold nanorods (GNRs) as exogenous OCT contrast agents. Specifically, we used anti-mouse CD45 coated GNRs to label mouse leukocytes and mPEG-coated GNRs to determine sensitivity of GNR detection in vivo inside mice retinae. We corroborated OCT observations with hyperspectral dark-field microscopy of formalin-fixed histological sections. Our results show that mouse leukocytes that otherwise do not produce OCT contrast can be labeled with GNRs leading to significant OCT intensity equivalent to a 0.5 nM GNR solution. Furthermore, GNRs injected intravenously can be detected inside retinal blood vessels at a sensitivity of ~0.5 nM, and GNR-labeled cells injected intravenously can be detected inside retinal capillaries by enhanced OCT contrast. We envision the unprecedented resolution and sensitivity of functionalized GNRs coupled with OCT to be adopted for longitudinal studies of retinal disorders. PMID- 27264493 TI - Photoacoustic imaging of angiogenesis in a subcutaneous islet transplant site in a murine model. AB - Islet transplantation (IT) is an established clinical therapy for select patients with type-1 diabetes. Clinically, the hepatic portal vein serves as the site for IT. Despite numerous advances in clinical IT, limitations remain, including early islet cell loss posttransplant, procedural complications, and the inability to effectively monitor islet grafts. Hence, alternative sites for IT are currently being explored, with the subcutaneous space as one potential option. When left unmodified, the subcutaneous space routinely fails to promote successful islet engraftment. However, when employing the previously developed subcutaneous "deviceless" technique, a favorable microenvironment for islet survival and function is established. In this technique, an angiocatheter was temporarily implanted subcutaneously, which facilitated angiogenesis to promote subsequent islet engraftment. This technique has been employed in preclinical animal models, providing a sufficient means to develop techniques to monitor functional aspects of the graft such as angiogenesis. Here, we utilize photoacoustic imaging to track angiogenesis during the priming of the subcutaneous site by the implanted catheter at 1 to 4 weeks postcatheter. Quantitative analysis on vessel densities shows gradual growth of vasculature in the implant position. These results demonstrate the ability to track angiogenesis, thus facilitating a means to optimize and assess the pretransplant microenvironment. PMID- 27264494 TI - Parasites, politics and public science: the promotion of biological control in Western Australia, 1900-1910. AB - Biological control of arthropods emerged as a scientific enterprise in the late nineteenth century and the orchard industry of California was an early centre of expertise. In 1900, as the Australian colonies prepared for federation, each had a government entomologist attached to its agriculture department. The hiring of George Compere from California by the Western Australian Department of Agriculture began a controversial chapter in the early history of biological control that was linked to a late, local popularization of acclimatization. Compere became known as the 'travelling entomologist' and for a decade brought 'parasites' of pest insects from overseas and released them in Perth. His antagonistic disciplinary rhetoric and inflated claims for the 'parasite theory' created conflict with his counterparts in the eastern states. The resulting inter state entomological controversy was played out in the press, revealing the political use of science for institutional and even state identity. It is a story of transnational exchanges, chance discoveries and popular public science: popular because of the promise of a simple, natural solution to agricultural insect pests and because of the public nature of the disputes it generated between the experts. This microcosm contributes to the global historiography of acclimatization, biological control, scientific exposition and the professionalization of agricultural science. PMID- 27264495 TI - 111 oriented gold nanoplatelets on multilayer graphene as visible light photocatalyst for overall water splitting. AB - Development of renewable fuels from solar light appears as one of the main current challenges in energy science. A plethora of photocatalysts have been investigated to obtain hydrogen and oxygen from water and solar light in the last decades. However, the photon-to-hydrogen molecule conversion is still far from allowing real implementation of solar fuels. Here we show that 111 facet-oriented gold nanoplatelets on multilayer graphene films deposited on quartz is a highly active photocatalyst for simulated sunlight overall water splitting into hydrogen and oxygen in the absence of sacrificial electron donors, achieving hydrogen production rate of 1.2 molH2 per gcomposite per h. This photocatalytic activity arises from the gold preferential orientation and the strong gold-graphene interaction occurring in the composite system. PMID- 27264496 TI - Paliperidone palmitate: Japanese postmarketing mortality results in patients with schizophrenia. AB - OBJECTIVE: Paliperidone palmitate once-monthly injectable (PP1M) is approved in Japan and other countries for the treatment of schizophrenia. During the 6 month Japanese early postmarketing phase vigilance (EPPV) period, 32 deaths were reported. This report reviews potential contributing factors to the fatal outcomes in the PP1M-treated population. RESEARCH DESIGN AND METHODS: All spontaneously reported adverse events following PP1M use received during EPPV from 19 November 2013 to 18 May 2014 were entered into the global safety database and these events were analyzed. RESULTS: During the EPPV period, 10,962 patients were estimated to have been treated with PP1M in Japan. The mortality reporting rate during this EPPV period was higher than that observed in the US or globally after PP1M launch (5.84, 0.43, and 0.38 per 1000 patient-years, respectively), but was consistent with the mortality incidence rates (10.2 per 1000 person years) observed during interventional clinical studies in Japan and in observational patient cohorts. Of the 32 deaths reported during the Japanese PP1M EPPV period, 19/32 (59.4%) were in patients over 50 years of age, 23/32 (71.9%) reported cardiovascular risk factors and 25/32 (78.1%) received antipsychotic polypharmacy. CONCLUSIONS: Based on this review of the 32 fatal cases in the PP1M EPPV period, the observed death rate does not necessarily result from a risk with PP1M treatment in Japanese patients. The higher mortality reporting rates in Japan may be attributed to a variety of factors: the effectiveness of mortality reporting in the unique Japanese EPPV program, the advanced age of the fatal cases, high cardiovascular risk factors, multiple underlying diseases and high antipsychotic polypharmacy among the cases with fatal outcomes. PMID- 27264497 TI - Light-induced water oxidation catalyzed by an oxido-bridged triruthenium complex with a Ru-O-Ru-O-Ru motif. AB - A MU-oxido-bridged triruthenium complex (RuT(2+)), formed by air-oxidation of a previously reported monoruthenium water oxidation catalyst (WOC), serves as an efficient photochemical WOC with the turnover frequency (TOF) and turnover number (TON) 0.90 s(-1) and 610, respectively. The crystal structures of RuT(2+) and its one-electron oxidized RuT(3+) are also reported. PMID- 27264498 TI - Perceptual Modalities Guiding Bat Flight in a Native Habitat. AB - Flying animals accomplish high-speed navigation through fields of obstacles using a suite of sensory modalities that blend spatial memory with input from vision, tactile sensing, and, in the case of most bats and some other animals, echolocation. Although a good deal of previous research has been focused on the role of individual modes of sensing in animal locomotion, our understanding of sensory integration and the interplay among modalities is still meager. To understand how bats integrate sensory input from echolocation, vision, and spatial memory, we conducted an experiment in which bats flying in their natural habitat were challenged over the course of several evening emergences with a novel obstacle placed in their flight path. Our analysis of reconstructed flight data suggests that vision, echolocation, and spatial memory together with the possible exercise of an ability in using predictive navigation are mutually reinforcing aspects of a composite perceptual system that guides flight. Together with the recent development in robotics, our paper points to the possible interpretation that while each stream of sensory information plays an important role in bat navigation, it is the emergent effects of combining modalities that enable bats to fly through complex spaces. PMID- 27264499 TI - Association analyses of depression and genes in the hypothalamus-pituitary adrenal axis. AB - OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme (ACE). METHODS: In total, 78 single nucleotide polymorphisms (SNPs) and one insertion/deletion polymorphism were genotyped. The study included 408 individuals with depression and 289 controls. In a subset of cases, the interaction between genetic variants and stressful life events (SLEs) was investigated. RESULTS: After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated with depression. One nominally significant interaction, most likely due to chance, was identified. CONCLUSION: The results indicate that ACE could be a potential candidate gene for depression. PMID- 27264501 TI - Dimethyldihydropyrene-cyclophanediene photochromic couple functionalized with terpyridyl metal complexes as multi-addressable redox- and photo-switches. AB - A series of dimethyldihydropyrene-appended metal complexes has been synthesized and thoroughly characterized using electrochemical and spectroscopic methods. The ring-opening reaction undergone by the dimethyldihydropyrene core under visible light irradiation proceeds much more efficiently when the metal complexes and the photochromic moiety are connected through a pyridinium-bridge vs a phenyl bridge. The clean electrochemical and photochemical responses of these hybrid systems make them good candidates for the conception of new multi-addressable photo- and redox-switches. PMID- 27264500 TI - Tridimensional finite element analysis of teeth movement induced by different headgear forces. AB - BACKGROUND: This study aimed to simulate the actions of low-pull (LP), high-pull (HP), and combined pull (CP) headgears (HGs) and to analyze tooth movement tendencies through finite element analysis. METHODS: Tomographic slices of a human maxilla with complete permanent dentition were processed by reconstruction software, and the triangular surface mesh was converted into non-uniform rational B-spline (NURBS) curves. An HG facial bow was also modulated in 3D. The teeth and bone were considered to have isotropic and linear behavior, whereas the periodontal ligament was considered to have non-linear and hyperelastic behavior. Data regarding the application points, directions and magnitudes of forces were obtained from the literature and from a dolichofacial patient with class II, division 1 malocclusion, who was treated with a CP HG. RESULTS: The CP HG promoted 37.1 to 41.1 %, and the HP HG promoted 19.1 to 31.9 % of LP distalization. The HP HG presented the highest intrusion, and the LP HG presented the highest extrusion of the first molar. The LP HG contracted the distal side, and the HP and CP HGs contracted the lingual and distobuccal roots of the second molar to a lesser degree. CONCLUSIONS: The LP HG promotes the greatest distalization, followed by the CP and HP HGs; the LP HG causes greater extrusion of the first molar, and the HP HG causes greater intrusion of the first molar. The LP HG causes greater contraction of the second molar than the HP HG. PMID- 27264502 TI - Effect of methacrylic acid beads on the sonic hedgehog signaling pathway and macrophage polarization in a subcutaneous injection mouse model. AB - Poly(methacrylic acid-co-methyl methacrylate) (MAA) beads promote a vascular regenerative response when used in diabetic wound healing. Previous studies reported that MAA beads modulated the expression of sonic hedgehog (Shh) and inflammation related genes in diabetic wounds. The aim of this work was to follow up on these observations in a subcutaneous injection model to study the host response in the absence of the confounding factors of diabetic wound healing. In this model, MAA beads improved vascularization in healthy mice of both sexes compared to control poly(methyl methacrylate) (MM) beads, with a stronger effect seen in males than females. MAA-induced vessels were perfusable, as evidenced from the CLARITY-processed images. In Shh-Cre-eGFP/Ptch1-LacZ non-diabetic transgenic mice, the increased vessel formation was accompanied by a higher density of cells expressing GFP (Shh) and beta-Gal (patched 1, Ptch1) suggesting MAA enhanced the activation of the Shh pathway. Ptch1 is the Shh receptor and a target of the pathway. MAA beads also modulated the inflammatory cell infiltrate in CD1 mice: more neutrophils and more macrophages were noted with MAA relative to MM beads at days 1 and 7, respectively. In addition, MAA beads biased macrophages towards a MHCII-CD206+ ("M2") polarization state. This study suggests that the Shh pathway and an altered inflammatory response are two elements of the complex mechanism whereby MAA-based biomaterials effect vascular regeneration. PMID- 27264503 TI - Corrigendum to "abnormal white matter integrity in antipsychotic-naive first episode psychosis patients assessed by a DTI principal component analysis" [Schizophr. Res. 162 (1-3) (march 2015) 14-21]. PMID- 27264504 TI - Reference Production as Search: The Impact of Domain Size on the Production of Distinguishing Descriptions. AB - When producing a description of a target referent in a visual context, speakers need to choose a set of properties that distinguish it from its distractors. Computational models of language production/generation usually model this as a search process and predict that the time taken will increase both with the number of distractors in a scene and with the number of properties required to distinguish the target. These predictions are reminiscent of classic findings in visual search; however, unlike models of reference production, visual search models also predict that search can become very efficient under certain conditions, something that reference production models do not consider. This paper investigates the predictions of these models empirically. In two experiments, we show that the time taken to plan a referring expression-as reflected by speech onset latencies-is influenced by distractor set size and by the number of properties required, but this crucially depends on the discriminability of the properties under consideration. We discuss the implications for current models of reference production and recent work on the role of salience in visual search. PMID- 27264505 TI - Do we need a new classification system for arteriosclerotic lesions in crural limb ischemia? Pros and Cons. PMID- 27264506 TI - Arterial stiffness, central blood pressures, wave reflections and acute hypertensive response in stroke. PMID- 27264507 TI - Combined effects of exercise capacity and coronary atherosclerotic burden on all cause mortality in asymptomatic Koreans. AB - BACKGROUND AND AIMS: Both exercise capacity and coronary artery calcium score (CACS) are important prognostic factors in cardiovascular outcome. Yet, whether there is a significant interaction between these two factors in influencing clinical outcome is still uncertain. This study investigated the combined effects of exercise capacity and CACS on all-cause mortality in an asymptomatic population. METHODS: From multicenter registry of health screening, a retrospective cohort of 25,972 asymptomatic subjects, who underwent both CACS and treadmill exercise test, was included in the final dataset for analysis. Outcome was defined as all-cause mortality, which was obtained from national mortality registry. RESULTS: The mean age of study subjects was 53.7 +/- 7.7 years and 81.5% of them were males. Median follow-up duration was 5.5 (IQR 3.6-7.5) years and 226 (0.9%) cases of all-cause mortality occurred. In multivariate Cox's proportional hazard model with interaction term, exercise capacity >=10 METs (HR 0.684, 95% CI 0.483-0.971) and CACS >=400 (HR 3.328, 95% CI 1.850-5.988) were significant predictors of all-cause mortality. In patients with higher exercise capacity, the effect of high CACS on all-cause mortality was significantly smaller than in those with lower exercise capacity. The HR for all-cause mortality of CACS >=400, in those with lower exercise capacity, is estimated to be about three times of that in those with higher exercise capacity (HR 3.328 in <10 METs vs. 1.108 in >=10 METs, p for interaction = 0.024) after adjustment for age, gender, fasting glucose, creatinine, alanine transaminase and albumin. CONCLUSIONS: The effect of high CACS on all-cause mortality is lessened by good exercise capacity in the asymptomatic population. Good physical fitness may reduce the adverse effect of high coronary atherosclerotic burden. PMID- 27264508 TI - UGT74B1 from Arabidopsis thaliana as a versatile biocatalyst for the synthesis of desulfoglycosinolates. AB - Thioglycosides, even if rare in Nature, have gained increased interest for their biological properties. Chemical syntheses of this class of compounds have been largely studied but little has been reported on their biosynthesis. Herein, combining experiments from the different fields of enzymology, bioorganic chemistry and molecular modeling, we wish to demonstrate the versatility of the glucosyltransferase UGT74B1 and its synthetic potency for the preparation of a variety of natural and unnatural desulfoglycosinolates. PMID- 27264509 TI - 2D QSAR and Virtual Screening based on Pyridopyrimidine Analogs of Epidermal Growth Factor Receptor Tyrosine Kinase. AB - BACKGROUND: Epidermal Growth Factor Receptor tyrosine kinase (EGFR) is an important anticancer drug target. Series of pyridopyrimidine analogs have been reported as EGFR inhibitors and they inhibit by binding to the ATP binding pocket of the tyrosine kinase domain. OBJECTIVE: To identify key properties of pyridopyrimidine analogs involved in the inhibition of the EGFR protein tyrosine kinase by developing 2D QSAR model. METHODS: Variable selection was performed by least absolute shrinkage and selection operator (LASSO) method and multiple linear regression (MLR) method was applied by using Build QSAR software to develop QSAR model. Model validation was done by Leave One Out method (LOO). Further, based on the bioactive and structural similarity, virtual screening was performed using Pubchem database. Using the developed QSAR model and Molinspiration server, PIC50 values and kinase inhibition activity were predicted for all the virtually screened compounds respectively. RESULTS: The best QSAR model consists of two descriptors namely Basak and MOE type descriptors, and has R2 = 0.8205, F= 57.129 & S = 0.308 and the validation results show significant statistics of R2/cv = 0.655, Average standard deviation = 0.416. 140 compounds were obtained from virtual screening and the predicted PIC50 of all these compounds are in the range of 4.73 - 6.78. All the compounds produce positive scores which suggest that the compounds may have good kinase inhibitory profile. CONCLUSION: This developed model may be useful to predict EGFR inhibition activity (PIC50) for the newly synthesized pyridopyrimidines analogs. PMID- 27264511 TI - Sir John Robert Vane. PMID- 27264512 TI - Antithrombin III in sepsis: does it really work? PMID- 27264510 TI - Breeding new forms of life: a critical reflection on extreme variances of bareback sex. AB - Many men who have sex with men (MSM) express feeling marginalized by discourses within public health and sexual health nursing that determine bareback sex is deviant and unsafe. Their resistance to risk-based discourses can be seen within radical sex practices such as deliberately becoming-infected with HIV (bug chasing) and breeding-infection (gift-giving). The metaphors of bug-chasing and gift-giving, particularly those spread across global online spaces, can influence the sexual experiences and practices of MSM. A metaphor analysis was conducted of Internet forums discussing HIV chasing and gifting metaphors, and showed a variety of discursive meanings, tactics and effects to the radical sex practice. A radical research approach was used to explore the processes of becoming infected and breeding-infection as determinant steps in the symbolic resistance of risk-based discourses, as well as the creation of new forms of life and community among MSM. Our analyses demonstrate how the gifting/chasing metaphors express MSM's marginalization as well as their lines of flight from having their practices captured within public health discourses. We hope to offer alternative nursing approaches for thinking through and engaging with transgressive and queer sexual practices. PMID- 27264513 TI - Beta-thalassemia mutations in Denizli province of Turkey. AB - Beta-thalassemia is one of the most common genetic disorders in Turkey as well as in several other Mediterranean countries presenting microcytosis and hemolytic anemia. The city of Denizli is located in the inner part of the Aegean geographical region of Turkey. The beta-thalassemia incidence in Denizli province is in between 2.6-3.7% reported by different researchers. According to our results; the IVS-1/nt-110 (G>A) is the most frequent mutation type in our province the same as other geographical regions of Turkey. Here we report also two HbD-Los Angeles/beta-thalassemia combinations, which are HbD-Los Angeles/codon 39 (C>T) and HbD-Los Angeles/IVS-1/nt-1 (G>A), respectively. In conclusion, our preliminary results show the heterogeneity of the beta thalassemia mutations in the province of Denizli. PMID- 27264514 TI - Splenectomy may not influence glutathione metabolism in children with beta thalassaemia major. AB - The present study was undertaken to evaluate glutathione and its related enzymes in beta-thalassaemia major and to elucidate the effect of splenectomy on glutathione metabolism. The study includes three groups, those are: healthy individuals (n= 35) taken as control, a group of beta-thalassaemia major children with intact spleen (n= 29) and a group of splenectomized beta-thalassaemia major children (n= 11). Levels of reduced glutathione, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenases in erythrocytes were estimated in all groups. Levels of glutathione p< 0.001 and glutathione reductase p< 0.05 in thalassaemic groups significantly increased, whereas glutathione peroxidase levels p< 0.005 were significantly decreased when compared to control. Glutathione and enzymes levels followed the same pattern in splenectomized group when compared to nonsplenectomized one; however the difference between the various parameters was not significant. Glutathione and its redox enzymes were severely disturbed in thalassaemic patients. Splenectomy, however appears to have no role in influencing glutathione metabolism in betathalassaemia major children. PMID- 27264515 TI - Pattern of adult leukemias at Al-Jomhori Educational Hospital, Sana'a, Yemen. AB - There is lack of information about leukemias in Yemen. The purpose of this study is to evaluate the pattern of adult leukemias at Al-Jomhori Educational Hospital in Sana'a, Yemen and to compare it with available data from Saudi Arabia. Data concerning age, sex, area of residence whether rural or urban and the type of leukemia were collected and analyzed. The age range of patients was 15 to 96 years. Diagnosis was based on bone marrow aspiration cytology and cytochemistry. Between November 1999 and November 2003 a total of 169 cases of leukemia were diagnosed. AML was the most common (39.1%) followed in descending order by CML (25.4%), ALL (23.7%) and CLL (11.8%). The male to female ratio was 1.14: 1 for all the types, 1.06: 1 for AML, 2.64: 1 for ALL, 0.65: 1 for CML and 1: 1 for CLL. AML was most common among patients aged 40-59 years old (30.3%) followed by >= 60 years old (25.8%). ALL was most common among young patients < 20 years old and CLL among elderly patients whereas CML was most common among middle aged patient. The rural to urban residence ratio was 2.8: 1 for all the types. Leukemia is an important health problem in Yemen and the pattern of adult leukemias is comparable in certain aspects to that reported from different regions of Saudi Arabia. The study recommends implementation of preventive, diagnostic and therapeutic strategies for leukemias in Yemen. PMID- 27264516 TI - Compound heterozygosity for two beta chain variants: the mildly unstable Hb Tyne (codon 5 Pro->Ser) and HbS (codon 6 Glu->Val). AB - Compound heterozygosity for Hb Tyne and HbS, that is very rare, was identified by direct DNA sequencing of the beta-globin gene in a Turkish patient. Hematological investigation of a girl at the age of 9 due to the presence of HbS (40.7%) led to the identification of a compound heterozygosity at codons 5-6. This was found to be the result of substitution of cytosine (C) for thymidine (T) at the fifth position and a substitution of adenine (A) for thymidine (T) at the sixth position of the beta globin gene. As a result of these mutations, the order of amino acids at codons 5-6 was changed from Pro-Glu to Ser-Val, respectively. Since the co-inheritance of Hb Tyne and HbS had not been reported in literature before, our case set an example for identification of coinheritance of Hb Tyne and HbS for the first time. Therefore, such cases may be considered as an important example for understanding the structural variants of hemoglobin and may provide important clues for critical amino acids responsible for stabilization of hemoglobin tetrameric structure and genetic counseling. PMID- 27264517 TI - Myelodysplastic syndrome with pseudoreticulocytosis. AB - A patient with myelodysplastic syndrome (MDS) with refractory anemia who had marked reticulocytosis in the absence of hemolytic anemia and/or blood loss is reported. Erythrocyte survival test showed that more than 50% of the patient's reticulocytes were still present on day seven. This should be due to the prolongation of reticulocyte maturation in MDS, and is known as pseudoreticulocytosis. This phenomenon which mimicks hemolytic anemia is an unusual presentation of myelodysplastic syndrome, with only 7 patients with pseudoreticulocytosis being reported previously. PMID- 27264518 TI - Case report of two haematopoietic stem cell transplanted patients with chronic graft-versus-host disease resembling acute viral hepatitis. AB - Chronic graft-versus-host disease (GVHD) of the liver usually presents as an indolent cholestatic syndrome associated with abnormalities in the skin, oral mucosa, and lacrimal glands observed beyond day 100 after allogeneic bone marrow transplantation. Because of its cholestatic nature, chronic liver GVHD is not generally considered in the differential diagnosis of markedly elevated serum transaminases and jaundice. However, sudden rise in serum transaminase levels after day 70 posttranplant should always raise the question of chronic liver GVHD. We report here two cases, in whom the presentation of chronic graft-versus host disease of the liver strongly resembled acute viral hepatitis. Chronic GVHD of the liver should also be taken into account in the differential diagnosis of marked elevations of liver enzymes in allogeneic stem cell transplant recipients and appropriate diagnostic and therapeutic measures should be applied. PMID- 27264519 TI - Images in Hematology. PMID- 27264520 TI - Reproducing politics: the politicisation of patients' identities and assisted reproduction in Poland and Sweden. AB - This article examines how discourses on assisted reproductive technologies are locally appropriated, translated or contested in the specific cultural and political contexts of Poland and Sweden. The aim is to investigate how two national patients' organisations, namely the Polish association Nasz Bocian and the Swedish organisation Barnlangtan, articulate rights claims in the context of reproductive technologies. To this end, we investigate how these organisations utilise specific context-dependent and affectively laden political vocabularies in order to mobilise politically, and discuss how each of these two groups gives rise to a different set of politicised reproductive identities. In order to trace which political vocabularies the respective organisations utilise to mobilise their respective rights claims, we draw primarily on political discourse theory and concepts of political grammars and empty signifiers. Lastly, we discuss which political reproductive identities emerge as a result of these different versions of political mobilisation around assisted reproductive technologies. PMID- 27264521 TI - Spatial confinement governs orientational order in patchy particles. AB - Orientational order in condensed matter plays a key role in determining material properties such as ferromagnetism, viscoelasticity or birefringence. We studied purely orientational ordering in closely-packed one-patch colloidal particles confined between flat substrates, where the particles can only rotate and are ordered via the sticky interaction between the patches. For the first time, we experimentally realized a rich variety of mesoscopic patterns through orientational ordering of colloids by controlling patch size and confinement thickness. The combination of experiment and numerical simulation reveals the decisive role of confinement: An ordered state(s) is selected from the (meta)stable options in bulk when it is commensurate with the system geometry and boundary conditions; otherwise, frustration induces a unique order. Our study offers a new means of systematic control over mesoscopic structures via orientational ordering in patchy particles. The system would also possess unique functionalities through the rotational response of the particles to external stimuli. PMID- 27264529 TI - Emticicia paludis sp. nov., isolated from wetland freshwater. AB - A novel bacterium, designated HMF3850T, was isolated from freshwater collected from the Gyeong-an wetland, Republic of Korea. Cells were Gram-stain-negative, aerobic, straight rods, non-motile, and oxidase- and catalase-positive. Growth was observed at pH 6.0-8.0 and at 10-30 degrees C on R2A agar. Comparative analysis of 16S rRNA gene sequences revealed that strain HMF3850T is a member of the genus Emticicia, sharing highest sequence similarities with Emticicia aquatica HMF2925T (96.7 % 16S rRNA gene sequence similarity), Emticicia sediminis JBR12T (95.0 %), Emticicia ginsengisoliGsoil 085T (94.9 %) and Emticicia oligotrophica DSM 17448T (94.7 %). The major fatty acids were iso-C15 : 0, summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and C16 : 0. The predominant respiratory quinone was MK-7. The major polar lipids were phosphatidylethanolamine, phosphatidylinositol, one unidentified aminophospholipid, two unidentified aminolipids and eight unidentified polar lipids. The DNA G+C content was 38.5 mol %. On the basis of the evidence presented in this study, strain HMF3850T represents a novel species of the genus Emticicia, for which the name Emticicia paludis sp. nov. is proposed. The type strain is HMF3850T (=KCTC 42851T=CECT 9087T). PMID- 27264530 TI - Interactive effects of dietary composition and hormonal treatment on reproductive development of cultured female European eel, Anguilla anguilla. AB - Farmed female eels were fed two experimental diets with similar proximate composition but different n-3 polyunsaturated fatty acid (PUFA) levels. Both diets had similar levels of arachidonic acid (ARA), while levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in one diet were approximately 4.5 and 2.6 times higher compared to the other diet, respectively. After the feeding period, each diet group was divided into two and each half received one of two hormonal treatments using salmon pituitary extract (SPE) for 13 weeks: i) a constant hormone dose of 18.75mg SPE/kg initial body weight (BW) and ii) a variable hormone dosage that increased from 12.5mg SPE/kg initial BW to 25mg SPE/kg initial BW. Results showed a significant interaction between diets and hormonal treatments on gonadosomatic index (GSI), indicating that the effect of broodstock diets on ovarian development depends on both nutritional status and hormonal regime. Females fed with higher levels of n-3 series PUFAs and stimulated with the constant hormonal treatment reached higher GSIs than those receiving the variable hormonal treatment. However, when females were fed lower levels of n-3 series PUFAs there was no difference in the effect of hormonal treatments on GSI. We also found that, independent of hormonal treatment, the diet with higher levels of n-3 series PUFAs led to the most advanced stages of oocyte development, such as germinal vesicle migration. Concentration of sex steroids (E2, T, and 11-KT) in the plasma did not differ between diets and hormonal treatments, but was significantly correlated with ovarian developmental stage. In conclusion, increasing dietary levels of n-3 PUFAs seemed to promote oocyte growth, leading to a more rapid progression of ovarian development in European eel subjected to hormonal treatment. PMID- 27264531 TI - Coexistence of two d-lactate-utilizing systems in Pseudomonas putida KT2440. AB - It is advantageous for rhizosphere-dwelling microorganisms to utilize organic acids such as lactate. Pseudomonas putida KT2440 is one of the most widely studied rhizosphere-dwelling model organisms. The P. putida KT2440 genome contains an NAD-dependent d-lactate dehydrogenase encoding gene, but mutation of this gene does not play a role in d-lactate utilization. Instead, it was found that d-lactate utilization in P. putida KT2440 proceeds via a multidomain NAD independent d-lactate dehydrogenase with a C-terminal domain containing several Fe-S cluster-binding motifs (Fe-S d-iLDH) and glycolate oxidase, which is widely distributed in various microorganisms. Both Fe-S d-iLDH and glycolate oxidase were identified to be membrane-bound proteins. Neither Fe-S d-iLDH nor glycolate oxidase is constitutively expressed but both of them can be induced by either enantiomer of lactate in P. putida KT2440. This study shows a case in which an environmental microbe contains two types of enzymes specific for d-lactate utilization. PMID- 27264532 TI - The impact of marital status at diagnosis on cancer survival in patients with differentiated thyroid cancer. AB - Previous studies have revealed that marital status influences the prognosis of patients with various types of cancer. We evaluated the influence of marriage on the survival outcomes in differentiated thyroid cancer (DTC). The Surveillance, Epidemiology and End Results (SEER) database between 2002 and 2012 was used to compare cancer-specific mortality in different marital status, and in each sex, age, and stage stratification by multivariate Cox regression model. In total, 61,077 eligible patients were identified. The widowed group had the highest proportion of women, elderly patients (>=45 years), and advanced stage III/IV tumor (P = 0.001), but the total thyroidectomy (TT) performed and radioisotopes therapy rates were lower than those in the married group. Married patients had a better cancer-specific survival (CSS) than the unmarried (P < 0.05). Further analysis showed that widowed patients always presented the lowest CSS compared with other groups. Widowed patients had a significant increased risk for CSS compared with married patients in males [hazard ratio (HR) 2.72, 95% confidence interval (CI): 1.59-4.65, P = 0.001], females (HR 2.02, 95% CI: 2.24-4.06, P = 0.001), young patients (<45, HR 28.12, 95% CI: 3.48-227.25, P = 0.002), elderly patients (>=45, HR 28.12, 95% CI: 2.97, 95% CI: 2.30-3.83, P = 0.001), stage I (HR 8.44, 95% CI: 4.05-17.59, P = 0.001), stage II (HR 3.64, 95% CI: 1.30-10.20, P = 0.014), stage III (HR 2.27, 95% CI: 1.08-4.78, P = 0.031), and stage IV (HR 2.63, 95% CI: 1.94-3.57, P = 0.001). These results showed that unmarried status, especially for widowhood, increased the risk of cancer mortality in DTC patients. PMID- 27264533 TI - An optimized xylene-free protein extraction method adapted to formalin-fixed paraffin embedded tissue sections for western blot analysis. AB - Deparaffinization of formalin-fixed paraffin embedded (FFPE) tissues with xylene currently remains a major challenge to the biomedical community. We developed an efficient xylene-free protocol to isolate proteins from archived FFPE human tissue sections. A total of 79 different types of FFPE tissue sections of 8 um thickness were obtained from various archived FFPE specimens. Deparaffinization was conducted by gently washing each section with around 1 ml of hot distilled water (~80 degrees C). The deparaffinized tissues were homogenized in lysis buffer, and the isolated proteins were quantified and efficiently resolved using western blot analysis for the presence of Protein kinase B (PKB/AKT) and beta actin. Moreover, a significant amount of proteins was successfully isolated with an average of 2.31 ug/ul. The migration pattern of AKT and beta-actin obtained from the specimens was similar to the positive control obtained from protein lysates prepared from in vitro cultured MDA231 cancer cell lines. AKT was successfully identified in all specimens, and beta-actin protein was resolved with an efficiency higher than 80%. The entire extraction procedure requires only 20 minutes. This newly developed technique is an efficient, safe, cost-effective, and rapid method to isolate proteins from FFPE tissue sections adequate for molecular analysis. PMID- 27264534 TI - Brain damage associated with apraxia of speech: evidence from case studies. AB - The site of crucial damage that causes acquired apraxia of speech (AOS) has been debated in the literature. This study presents five in-depth cases that offer insight into the role of brain areas involved in AOS. Four of the examined participants had a primary impairment of AOS either with (n = 2) or without concomitant mild aphasia (n = 2). The fifth participant presented with a lesion relatively isolated to the left anterior insula (AIns-L), damage that is rarely reported in the literature, but without AOS. Taken together, these cases challenge the role of the AIns-L and implicate the left motor regions in AOS. PMID- 27264536 TI - Calpain A controls mitotic synchrony in the Drosophila blastoderm embryo. AB - The beautiful mitotic waves that characterize nuclear divisions in the early Drosophila embryo have been the subject of intense research to identify the elements that control mitosis. Calcium waves in phase with mitotic waves suggest that calcium signals control this synchronized pattern of nuclear divisions. However, protein targets that would translate these signals into mitotic control have not been described. Here we investigate the role of the calcium-dependent protease Calpain A in mitosis. We show that impaired Calpain A function results in loss of mitotic synchrony and ultimately halted embryonic development. The presence of defective microtubules and chromosomal architecture at the mitotic spindle during metaphase and anaphase and perturbed levels of Cyclin B indicate that Calpain A is required for the metaphase-to-anaphase transition. Our results suggest that Calpain A functions as part of a timing module in mitosis, at the interface between calcium signals and mitotic cycles of the Drosophila embryo. PMID- 27264535 TI - Spatial distribution of predicted transcription factor binding sites in Drosophila ChIP peaks. AB - In the development of the Drosophila embryo, gene expression is directed by the sequence-specific interactions of a large network of protein transcription factors (TFs) and DNA cis-regulatory binding sites. Once the identity of the typically 8-10bp binding sites for any given TF has been determined by one of several experimental procedures, the sequences can be represented in a position weight matrix (PWM) and used to predict the location of additional TF binding sites elsewhere in the genome. Often, alignments of large (>200bp) genomic fragments that have been experimentally determined to bind the TF of interest in Chromatin Immunoprecipitation (ChIP) studies are trimmed under the assumption that the majority of the binding sites are located near the center of all the aligned fragments. In this study, ChIP/chip datasets are analyzed using the corresponding PWMs for the well-studied TFs; CAUDAL, HUNCHBACK, KNIRPS and KRUPPEL, to determine the distribution of predicted binding sites. All four TFs are critical regulators of gene expression along the anterio-posterior axis in early Drosophila development. For all four TFs, the ChIP peaks contain multiple binding sites that are broadly distributed across the genomic region represented by the peak, regardless of the prediction stringency criteria used. This result suggests that ChIP peak trimming may exclude functional binding sites from subsequent analyses. PMID- 27264537 TI - The 'tissue press': a new device to flatten fresh tissue during ex vivo confocal microscopy examination. PMID- 27264538 TI - Clinical features of SMARCA2 duplication overlap with Coffin-Siris syndrome. AB - Coffin-Siris syndrome is a rare congenital malformation and intellectual disability syndrome. Mutations in at least seven genes have been identified. Here, we performed copy number analysis in 37 patients with features of CSS in whom no causative mutations were identified by exome sequencing. We identified a patient with a 9p24.3-p22.2 duplication and another patient with the chromosome der(6)t(6;9)(p25;p21)mat. Both patients share a duplicated 15.8-Mb region containing 46 protein coding genes, including SMARCA2. Dominant negative effects of SMARCA2 mutations may contribute to Nicolaides-Baraitser syndrome. We conclude that their features better resemble Coffin-Siris syndrome, rather than Nicolaides Baraitser syndrome and that these features likely arise from SMARCA2 over-dosage. Pure 9p duplications (not caused by unbalanced translocations) are rare. Copy number analysis in patients with features that overlap with Coffin-Siris syndrome is recommended to further determine their genetic aspects. (c) 2016 Wiley Periodicals, Inc. PMID- 27264539 TI - IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES). AB - Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5' untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/. PMID- 27264540 TI - Incidental prenatal detection of DMD gene deletion using array comparative genomic hybridization. PMID- 27264541 TI - BMP signaling regulates the fate of chondro-osteoprogenitor cells in facial mesenchyme in a stage-specific manner. AB - BACKGROUND: Lineage tracing has shown that most of the facial skeleton is derived from cranial neural crest cells. However, the local signals that influence postmigratory, neural crest-derived mesenchyme also play a major role in patterning the skeleton. Here, we study the role of BMP signaling in regulating the fate of chondro-osteoprogenitor cells in the face. RESULTS: A single Noggin soaked bead inserted into stage 15 chicken embryos induced an ectopic cartilage resembling the interorbital septum within the palate and other midline structures. In contrast, the same treatment in stage 20 embryos caused a loss of bones. The molecular basis for the stage-specific response to Noggin lay in the simultaneous up-regulation of SOX9 and downregulation of RUNX2 in the maxillary mesenchyme, increased cell adhesiveness as shown by N-cadherin induction around the beads and increased RA pathway gene expression. None of these changes were observed in stage 20 embryos. CONCLUSIONS: These experiments demonstrate how slight changes in expression of growth factors such as BMPs could lead to gain or loss of cartilage in the upper jaw during vertebrate evolution. In addition, BMPs have at least two roles: one in patterning the skull and another in regulating the skeletogenic fates of neural crest-derived mesenchyme. Developmental Dynamics 245:947-962, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27264543 TI - The Brainstem Tau Cytoskeletal Pathology of Alzheimer's Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance. AB - The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer's disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology. PMID- 27264544 TI - Application of flow cytometry for evaluating clinical prognosis and histopathological grade of human glioma. AB - OBJECTIVES: Flow cytometry was applied to predict the biological parameters of tumor behavior based on the DNA content distribution of tumors. We used flow cytometry to determine the number of cell cycles for the characterization of intracranial gliomas and its possible prognostic role. METHODS: Flow cytometric analysis of the DNA content was performed for 37 fresh operative glioma specimens. The expression of Ki-67 in glioma specimens was detected using immunohistochemistry staining. The check points of G2/M-phase fractions, cyclin B, and pCdk1 (Y15) were analyzed using Western immunoblotting. RESULTS: Compared to low-grade (grade I/II) gliomas, significant differences in the Ki-67, cyclin B, G2/M-phase, and S+G2/M-phase expressions were found in high-grade (grade III/IV) gliomas. Furthermore, receiver operating characteristic (ROC) analysis indicated optimal cutoff points for the G2/M-phase and S+G2/M-phase fractions of 13.47 and 17.26%, respectively, which can be used to differentiate cases with low and high-grade gliomas. Additionally, both G2/M-phase and S+G2/M-phase fractions had significant association with the expression of Ki-67 in the gliomas. The gliomas were classified by the DNA content. We found that patients with high grade glioma had worse survival rate than patients with low-grade glioma. Meanwhile, ROC curve analysis gave cutoffs for G2/M-phase of 9.4% and for S+G2/M phase fractions of 15.04% as best predicting survival. The patients with glioma had poor survival when the levels of G2/M-phase and S+G2/M-phase were more than 9.4 and 15.04%, respectively. In contrast, no significant association between the DNA content of glioma patients and their age, tumor recurrence, and tumor size was found. DISCUSSION: Our results indicate that flow cytometry analysis for G2/M phase and S+G2/M-phase fractions can be used for tumor grading for rapidly differentiating low- from high-grade gliomas. PMID- 27264545 TI - E-learning for grass-roots emergency public health personnel: Preliminary lessons from a national program in China. AB - In China, grass-roots emergency public health personnel have relatively limited emergency response capabilities and they are constantly required to update their professional knowledge and skills due to recurring and new public health emergencies. However, professional training, a principal solution to this problem, is inadequate because of limitations in manpower and financial resources at grass-roots public health agencies. In order to provide a cost-effective and easily expandable way for grass-roots personnel to acquire knowledge and skills, the National Health Planning Commission of China developed an emergency response information platform and provided trial access to this platform in Anhui and Heilongjiang provinces in China. E-learning was one of the modules of the platform and this paper has focused on an e-learning pilot program. Results indicated that e-learning had satisfactorily improved the knowledge and ability of grass-roots emergency public health personnel, and the program provided an opportunity to gain experience in e-course design and implementing e-learning. Issues such as the lack of personalized e-courses and the difficulty of evaluating the effectiveness of e-learning are topics for further study. PMID- 27264542 TI - Specific threonine-4 phosphorylation and function of RNA polymerase II CTD during M phase progression. AB - Dynamic phosphorylation of Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 heptad-repeats in the C-terminal domain (CTD) of the large subunit coordinates progression of RNA polymerase (Pol) II through the transcription cycle. Here, we describe an M phase specific form of Pol II phosphorylated at Thr4, but not at Tyr1, Ser2, Ser5, and Ser7 residues. Thr4 phosphorylated Pol II binds to centrosomes and midbody and interacts with the Thr4-specific Polo-like kinase 1. Binding of Pol II to centrosomes does not require the CTD but may involve subunits of the non canonical R2TP-Prefoldin-like complex, which bind to and co-localize with Pol II at centrosomes. CTD Thr4 mutants, but not Ser2 and Ser5 mutants, display severe mitosis and cytokinesis defects characterized by multipolar spindles and polyploid cells. We conclude that proper M phase progression of cells requires binding of Pol II to centrosomes to facilitate regulation of mitosis and cytokinesis in a CTD Thr4-P dependent manner. PMID- 27264546 TI - alphaB-Crystallin interacts and attenuates the tyrosine phosphatase activity of Shp2 in cardiomyocytes under mechanical stress. AB - The small heat shock protein alphaB-Crystallin (CryAB, HspB5) and SH2 domain containing tyrosine phosphatase 2 (Shp2) are important molecules in heart response to pathophysiological stress. Here we show that CryAB interacts with and potentially regulates Shp2 catalytic activity in stretched cardiomyocytes. Such an interaction requires CryAB oligomer to attenuate Shp2 activation. Stretched cardiomyocytes show a robust CryAB/Shp2 association accompanied by a reduction in the Shp2 phosphatase activity. Accordingly, CryAB knock-down in cardiomyocytes enhances Shp2 activity induced by mechanical stress. These results revealed a new role for CryAB, as a modulator of Shp2 phosphatase activity during a functionally relevant stimulus in cardiomyocytes. PMID- 27264547 TI - A Knowledge Translation Programme to Increase the Utilization of Thoracic Spine Mobilization and Manipulation for Patients with Neck Pain. AB - BACKGROUND: There is extensive evidence that mobilization and manipulation of the thoracic spine is associated with improved outcomes in patients with neck pain. However, these evidence-based techniques are not always utilized. Successful knowledge translation programmes are needed to move the best available evidence to clinical practice. The purpose of the present research was to evaluate the effects of a structured knowledge translation programme on the frequency of manual therapy techniques performed by physical therapists on patients with neck pain. METHODS: Prior to our intervention, we assessed physical therapists' use of thoracic spine intervention for the treatment of neck pain and their knowledge of the evidence. We delivered a multimodal knowledge translation programme and then reassessed their use and knowledge of the interventions. RESULTS: The majority of our physical therapists increased the use of thoracic spine techniques for their patients with neck pain. The increase was greater in those who used the techniques infrequently. Overall knowledge of the evidence appeared unchanged. DISCUSSION: Knowledge translation programmes are essential in ensuring clinical use of evidence-based practice. Our programme results, although on a small scale and not statistically significant, showed a positive trend toward increased thoracic spine manual therapy use for neck pain. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 27264548 TI - An Investigation into the Scale and Impact of Self-Reported Foot Problems Associated with Systemic Lupus Erythematosus: A Study Protocol and Survey Questionnaire Development. AB - BACKGROUND: Systemic lupus erythematosus (SLE) can manifest with arthralgia and myalgia, and, in severe cases, disorganization of the joints and tendon rupture. Further, Raynaud's phenomenon and other circulatory problems such as vasculitis have been reported, and may be associated with loss of sensation and ulcers. Associated with impaired peripheral neurovascular function there is the potential for changes in tissue viability leading to thinning of the skin or callus formation. In addition, resistance to infections may be reduced, such as fungal infection of the skin and nails, bacterial infection associated with wounds and viral infections such as verruca. There is a dearth of evidence for the effects of SLE in the foot, the prevalence of foot problems in SLE and the impact of these on the individual. In addition, it is not known if people with SLE and foot problems have access to specialist care through foot health services. Hence, there is a need to investigate the scale of foot problems associated with SLE. In order to achieve this, a questionnaire needs to be developed in order to carry out a national survey in England. METHODS: The items required for the questionnaire were generated using a focus group, which comprised patient advisers with SLE, consultants who specialized in SLE, specialist rheumatology podiatrists and specialist rheumatology nurses. From this consensus approach to the item generation, the draft questionnaire was developed with agreement on themes, question format and overall structure. Additionally, the Manchester Pain and Disability Questionnaire was included in order to capture levels of pain and associated disability. An iterative process followed, with feedback from the focus group reducing the number of other items from 53, until the penultimate version of questionnaire was produced with 50 items. Following on from this, a process of cognitive debriefing was used with two people with SLE who were naive to the questionnaire. Minor changes to two questions and the layout was required before a final version of the questionnaire was produced. DISCUSSION: The questionnaire will be used for a study which aims to identify the frequency of patients' self-reported foot problems, the impact of foot problems on their lives and the status of foot care provision. This will be achieved through a survey of people with SLE across six clinical sites and interviews with some people in order to explore their experience of foot problems. The results from the present study will provide the information required to inform further research. In addition, it could potentially inform the design and delivery of foot health information and services to this patient group. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 27264549 TI - Inpatient Walking Activity to Predict Readmission in Older Adults. AB - OBJECTIVE: To compare the 30-day readmission predictive power of in-hospital walking activity and in-hospital activities of daily living (ADLs) in older acutely ill patients. In addition, we sought to identify preliminary walking thresholds that could support the targeting of interventions aimed at minimizing rehospitalizations. DESIGN: Prospective, observational clinical cohort study. Step counts during hospitalization were assessed via accelerometry. ADL function was assessed within 48 hours of admission. SETTING: Acute care hospital. PARTICIPANTS: One hundred sixty-four ambulatory persons aged 65 years and older admitted to the hospital from the community with an acute medical illness. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Readmission back to the index hospital (yes vs no) within 30 days of discharge. RESULTS: Twenty-six patients (15.8%) were readmitted within 30 days of discharge. Walking activity during hospitalization was more strongly and significantly associated with 30-day readmission (odds ratio=0.90; 95% confidence interval, 0.82-0.98) than ADL function (odds ratio=0.45; 95% confidence interval, 0.14-1.45) after adjusting for relevant readmission risk factors. The predictive accuracy (area under the curve) was highest for models that included walking activity and changed little with the addition of ADLs. A walking threshold of 275 steps or more per day identified patients at reduced 30-day readmission risk. CONCLUSIONS: Walking activity was a stronger predictor of readmission than ADLs. Monitoring patient activity during hospitalization may provide clinicians with valuable information on early readmission risk not captured by measures of ADLs. Further study is needed to replicate these findings and monitor walking activity posthospitalization to further advance our understanding of readmission risk. PMID- 27264550 TI - Improved Sensitivity for the Qualitative and Quantitative Analysis of Active Ricin by MALDI-TOF Mass Spectrometry. AB - Ricin is a highly toxic protein which causes cell death by blocking protein synthesis and is considered a potential bioterrorism agent. Rapid and sensitive detection of ricin toxin in various types of sample matrices is needed as an emergency requirement for public health and antibioterrorism response. An in vitro MALDI TOF MS-based activity assay that detects ricin mediated depurination of synthetic substrates was improved through optimization of the substrate, reaction conditions, and sample preparation. In this method, the ricin is captured by a specific polycolonal antibody followed by hydrolysis reaction. The ricin activity is determined by detecting the unique cleavage product of synthetic oligomer substrates. The detection of a depurinated substrate was enhanced by using a more efficient RNA substrate and optimizing buffer components, pH, and reaction temperature. In addition, the factors involved in mass spectrometry analysis, such as MALDI matrix, plate, and sample preparation, were also investigated to improve the ionization of the depurinated product and assay reproducibility. With optimized parameters, the limit of detection of 0.2 ng/mL of ricin spiked in buffer and milk was accomplished, representing more than 2 orders of magnitude enhancement in assay sensitivity. Improving assay's ruggeddness or reproducibility also made it possible to quantitatively detect active ricin with 3 orders of magnitude dynamic range. PMID- 27264551 TI - Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications. AB - In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia. PMID- 27264552 TI - A safe, simple and efficient doxorubicin prodrug hybrid micelle for overcoming tumor multidrug resistance and targeting delivery. AB - A pH-sensitive prodrug, TPGS-CHN-DOX, was introduced by conjugating anticancer drug, doxorubicin (DOX), onto d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) via a cleavable Schiff base linkage. The prodrug was mixed with a PEGylated lipid to form a simple but multifunctional hybrid micelle system, which can realize high drug loading capability and biocompatibility, extended blood circulation time, inhibited drug resistance in cancer cells, improved therapeutic response, reduced side effects, and easy functionalities for targeting delivery. The hybrid micelles exhibited in vitro pH-sensitive drug release, enhanced cellular uptake and strengthened cytotoxicity on both drug sensitive human breast cancer MCF-7 and resistant MCF-7/ADR cells. P-glycoprotein functional inhibition and mitochondria-associated cell apoptosis induced by TPGS were thought to play an important role in overcoming the multidrug resistance. As a result, the hybrid micelles demonstrated good anticancer efficacy in MCF-7/ADR xenograft model. Additionally, after modifying with a tumor-specific targeting peptic ligand, cRGD, the tumor growth/metastasis inhibition was further evidenced in integrin receptor overexpressed melanoma cancer B16F10 and even murine hepatocarcinoma H22 models. This TPGS-based pH-sensitive prodrug provides a safe and "Molecular economical" way in the rational design of prodrugs for overcoming multidrug resistance and targeting delivery, which can improve the potency for clinical use. PMID- 27264553 TI - Endosomal acidic pH-induced conformational changes of a cytosol-penetrating antibody mediate endosomal escape. AB - Endosomal escape after endocytosis is a critical step for protein-based agents to exhibit their effects in the cytosol of cells. However, antibodies internalized into cells by endocytosis cannot reach the cytosol due to their inability to escape from endosomes. Here, we report a unique endosomal escape mechanism of the IgG-format TMab4 antibody, which can reach the cytosol of living cells after internalization. Dissociation of TMab4 from its cell surface receptor heparan sulfate proteoglycan by activated heparanase in acidified early endosomes and then local structural changes of the endosomal escape motif of TMab4 in response to the acidified endosomal pH were critical for the formation of membrane pores through which TMab4 escaped into the cytosol. Identification of structural determinants of endosomal escape led us to generate a TMab4 variant with ~3-fold improved endosomal escape efficiency. Our finding of the endosomal escape mechanism of the cytosol-penetrating antibody and its improvement will establish a platform technology that enables a full-length IgG antibody to directly target cytosolic proteins. PMID- 27264554 TI - Identification of 6-Hydroxymellein Synthase and Accessory Genes in the Lichen Cladonia uncialis. AB - A transcribed polyketide synthase (PKS) gene has been identified in the lichen Cladonia uncialis. The complete nucleotide sequence of this PKS was determined from the amplified cDNA, and an assignment of individual domains was accomplished by homology searching using AntiSMASH. A scan of the complete genome sequence of C. uncialis revealed the accessory genes associated with this PKS gene. A homology search has identified that several genes in this cluster are similar to genes responsible for the biosynthesis of terrein in Aspergillus terreus. This permitted assignment of putative function to each of the genes in this new C. uncialis cluster. It is proposed that this gene cluster is responsible for the biosynthesis of a halogenated iscoumarin. This is the first report linking a gene cluster to a halogenated metabolite in lichen. PMID- 27264555 TI - The importance of the Lewis base in lithium mediated metallation and bond cleavage reaction of allyl amines and allyl phosphines. AB - Metallation of two analogous N- and P-allyl molecules Ph2NCH2CHCH2 and Ph2PCH2CHCH2 with nBuLi have shown contrasting reactivities based on the choice of Lewis donor. With metallation of the alpha carbon atom was achieved regardless of the Lewis donor used while in comparison metallation of showed an unexpected donor denticity dependence with P-C bond clevage induced with the tri-dentate PMDETA. Complementary DFT and solution studies rationalise this outcome. PMID- 27264556 TI - Molecular mechanisms of DNA damage recognition for mammalian nucleotide excision repair. AB - For faithful DNA repair, it is crucial for cells to locate lesions precisely within the vast genome. In the mammalian global genomic nucleotide excision repair (NER) pathway, this difficult task is accomplished through multiple steps, in which the xeroderma pigmentosum group C (XPC) protein complex plays a central role. XPC senses the presence of oscillating 'normal' bases in the DNA duplex, and its binding properties contribute to the extremely broad substrate specificity of NER. Unlike XPC, which acts as a versatile sensor of DNA helical distortion, the UV-damaged DNA-binding protein (UV-DDB) is more specialized, recognizing UV-induced photolesions and facilitating recruitment of XPC. Recent single-molecule analyses and structural studies have advanced our understanding of how UV-DDB finds its targets, particularly in the context of chromatin. After XPC binds DNA, it is necessary to verify the presence of damage in order to avoid potentially deleterious incisions at damage-free sites. Accumulating evidence suggests that XPA and the helicase activity of transcription factor IIH (TFIIH) cooperate to verify abnormalities in DNA chemistry. This chapter reviews recent findings about the mechanisms underlying the efficiency, versatility, and accuracy of NER. PMID- 27264558 TI - When DNA repair goes wrong: BER-generated DNA-protein crosslinks to oxidative lesions. AB - Free radicals generate an array of DNA lesions affecting all parts of the molecule. The damage to deoxyribose receives less attention than base damage, even though the former accounts for ~20% of the total. Oxidative deoxyribose fragments (e.g., 3'-phosphoglycolate esters) are removed by the Ape1 AP endonuclease and other enzymes in mammalian cells to enable DNA repair synthesis. Oxidized abasic sites are initially incised by Ape1, thus recruiting these lesions into base excision repair (BER) pathways. Lesions such as 2-deoxypentos-4 ulose can be removed by conventional (single-nucleotide) BER, which proceeds through a covalent Schiff base intermediate with DNA polymerase beta (Polbeta) that is resolved by hydrolysis. In contrast, the lesion 2-deoxyribonolactone (dL) must be processed by multinucleotide ("long-patch") BER: attempted repair via the single-nucleotide pathway leads to a dead-end, covalent complex with Polbeta cross- linked to the DNA by an amide bond. We recently detected these stable DNA protein crosslinks (DPC) between Polbeta and dL in intact cells. The features of the DPC formation in vivo are exactly in keeping with the mechanistic properties seen in vitro: Polbeta-DPC are formed by oxidative agents in line with their ability to form the dL lesion; they are not formed by non-oxidative agents; DPC formation absolutely requires the active-site lysine-72 that attacks the 5' deoxyribose; and DPC formation depends on Ape1 to incise the dL lesion first. The Polbeta-DPC are rapidly processed in vivo, the signal disappearing with a half life of 15-30min in both mouse and human cells. This removal is blocked by inhibiting the proteasome, which leads to the accumulation of ubiquitin associated with the Polbeta-DPC. While other proteins (e.g., topoisomerases) also form DPC under these conditions, 60-70% of the trapped ubiquitin depends on Polbeta. The mechanism of ubiquitin targeting to Polbeta-DPC, the subsequent processing of the expected 5'-peptidyl-dL, and the biological consequences of unrepaired DPC are important to assess. Many other lyase enzymes that attack dL can also be trapped in DPC, so the processing mechanisms may apply quite broadly. PMID- 27264559 TI - Protein damage, radiation sensitivity and aging. AB - This paper promotes a concept that protein damage determines radiation resistance and underlies aging and age-related diseases. The first bottleneck in cell recovery from radiation damage is functional (proteome) rather than informational (DNA), since prokaryotic and eukaryotic cell death correlates with incurred protein, but not DNA, damage. Proteome protection against oxidative damage determines survival after ionizing or UV irradiation, since sufficient residual proteome activity is required to turn on the DNA damage response activating DNA repair and protein renewal processes. Extreme radiation and desiccation resistance of rare bacterial and animal species is accounted for by exceptional constitutive proteome protection against oxidative damage. After excessive radiation their well-protected proteome faithfully reconstitutes a transcription competent genome from hundreds of DNA fragments. The observation that oxidative damage targeted selectively to cellular proteins results in aging-like phenotypes suggests that aging and age-related diseases could be phenotypic consequences of proteome damage patterns progressing with age. PMID- 27264557 TI - DNA polymerase theta (POLQ), double-strand break repair, and cancer. AB - DNA polymerase theta (pol theta) is encoded in the genomes of many eukaryotes, though not in fungi. Pol theta is encoded by the POLQ gene in mammalian cells. The C-terminal third of the protein is a family A DNA polymerase with additional insertion elements relative to prokaryotic homologs. The N-terminal third is a helicase-like domain with DNA-dependent ATPase activity. Pol theta is important in the repair of genomic double-strand breaks (DSBs) from many sources. These include breaks formed by ionizing radiation and topoisomerase inhibitors, breaks arising at stalled DNA replication forks, breaks introduced during diversification steps of the mammalian immune system, and DSB induced by CRISPR Cas9. Pol theta participates in a route of DSB repair termed "alternative end joining" (altEJ). AltEJ is independent of the DNA binding Ku protein complex and requires DNA end resection. Pol theta is able to mediate joining of two resected 3' ends harboring DNA sequence microhomology. "Signatures" of Pol theta action during altEJ are the frequent utilization of longer microhomologies, and the insertion of additional sequences at joining sites. The mechanism of end-joining employs the ability of Pol theta to tightly grasp a 3' terminus through unique contacts in the active site, allowing extension from minimally paired primers. Pol theta is involved in controlling the frequency of chromosome translocations and preserves genome integrity by limiting large deletions. It may also play a backup role in DNA base excision repair. POLQ is a member of a cluster of similarly upregulated genes that are strongly correlated with poor clinical outcome for breast cancer, ovarian cancer and other cancer types. Inhibition of pol theta is a compelling approach for combination therapy of radiosensitization. PMID- 27264560 TI - Spatiotemporal expression pattern of the zebrafish aquaporin 8 family during early developmental stages. AB - Aquaporin 8 (Aqp8) is a transmembrane protein that is selectively permeated by water and some small solutes, and physiologically contributes to acid-base equilibrium in the gastrointestinal tract. Here, we described the characterization and spatiotemporal expression pattern of zebrafish aqp8 (zaqp8) gene family, including zaqp8a.1, zaqp8a.2, and zaqp8b, during the early developmental stages. The expression of zaqp8a.1 started first in the lateral plate mesoderm at the 12-somite stage (ss) and then expanded sequentially to the dorsal aorta, intersegmental blood vessels and then to the dorsal longitudinal anastomotic vessel at 24 h post fertilization (hpf). At 28 hpf, expression of zaqp8a.1 was also detected in the embryonic heart tube. Four days post fertilization (dpf), strong zaqp8a.1 expression was detected in the gastrointestinal tract and liver. By 72 hpf, the expression of zaqp8a.2 was first detected in the primitive gut region but not detected in the liver. The expression of zaqp8b was first detected in the intermediate mesoderm at 10 ss. From 24 hpf to 6 dpf, the proximal convoluted segment of the embryonic kidney was marked by zaqp8b expression Overall, these differential expression patterns of aqp8a.1, aqp8a.2, and aqp8b suggest that they possibly play distinct roles throughout the embryonic development by controlling or maintaining organ-specific cellular water homeostasis. Our study provides new evidence that organogenesis requires differential roles of Aqp8 proteins in zebrafish. PMID- 27264561 TI - Novel application of the controlled allergen challenge facility model. PMID- 27264562 TI - Summer camps and food allergy: What do we not know? PMID- 27264563 TI - Social media and the allergy practice. PMID- 27264564 TI - Association of wider neck circumference and asthma in obese children. AB - BACKGROUND: Obesity is a well-established risk factor for asthma. Previous studies have reported that central obesity is associated with asthma. OBJECTIVE: To investigate the association between fat distribution, which is determined by anthropometric measures, including neck circumference (NC), and asthma in school aged children. METHODS: Children diagnosed as having asthma were enrolled along with controls who were admitted to our outpatient department with allergic symptoms, such as rhinitis, urticaria and atopic dermatitis. Anthropometric measures, including height, weight, NC, waist circumference, and hip circumference, were obtained. Skin prick tests, blood eosinophil counts, and serum total IgE level measurements were performed. RESULTS: A total of 196 children (92 male [46.9%]) were included. Asthma was present in 102 patients (52.1%). Ninety-one of the patients (46.4%) were overweight, and 45 patients (22.9%) were obese. The NC of children with asthma was significantly higher than that of children in the control group. Grades defined according to NC percentiles were also significantly different between groups. In children with asthma, the prevalence of children with an NC higher than the 90th percentile (grade 6) was more frequent when compared with controls. The median NC of obese-overweight children with asthma was significantly higher compared with obese-overweight controls without asthma. Results of multivariable logistic regression analysis revealed that the presence of an NC in the greater than 90th percentile was associated with asthma in obese-overweight children. CONCLUSION: This study found that NC, which is a simple anthropometric measure, is associated with asthma in obese children. PMID- 27264565 TI - Association between chronic idiopathic urticaria and hypertension: A population based retrospective cohort study. AB - BACKGROUND: Chronic idiopathic urticaria (CIU) is defined as urticaria that is not caused by external triggers. The pathogenesis of CIU remains unknown. A previous study investigated whether hypertension is associated with extended duration of CIU. OBJECTIVE: To investigate the possible association between CIU and hypertension. METHODS: We performed a population-based retrospective cohort study of 2,460 patients with CIU and 9,840 age-, sex-, and index year-matched comparison patients, using the National Health Insurance of Taiwan database. The median follow-up periods were 7.13 years for the CIU cohort and 7.20 years for the non-CIU cohort. The distributions by sex and age were similar for both cohorts. RESULTS: The CIU cohort had a 1.37-fold (95% CI, 1.22-1.53) greater risk of developing subsequent hypertension than the non-CIU cohort after adjusting for sex, age, comorbidities, and nonsedating antihistamine use. CONCLUSION: This nationwide retrospective cohort study found that CIU is associated with a higher future risk of hypertension after adjusting for sex, age, comorbidities, and nonsedating antihistamine use. The detailed pathophysiologic mechanisms require further clarification in prospective studies. PMID- 27264566 TI - Approach to food allergy diagnosis and management by nonspecialty practitioners. PMID- 27264568 TI - Authors' response. PMID- 27264567 TI - Dog allergen immunotherapy and allergy to furry animals. PMID- 27264569 TI - [Reflection on tuberculosis infection]. PMID- 27264570 TI - [Annual tuberculosis diagnosis and treatment review (2015)]. PMID- 27264571 TI - [Preventive therapy for tuberculosis and its challenges]. PMID- 27264572 TI - [The chemotharapy of latent tuberculosis infection]. PMID- 27264573 TI - [Latent tuberculosis infection among healthcare workers]. PMID- 27264574 TI - [Latent tuberculosis infection sreening and preventive therapy in students]. PMID- 27264575 TI - [Immunologic mechanism and immune intervention therapy of latent tuberculosis infection]. PMID- 27264576 TI - [Ventilation strategies and choices in acute respiratory distress syndrome]. PMID- 27264577 TI - [Animal models of obstructive sleep apnea]. PMID- 27264578 TI - [Genomics of chronic obstructive pulmonary disease]. PMID- 27264579 TI - Orbital medial wall fractures: purely endoscopic endonasal repair with polyethylene implants. PMID- 27264580 TI - The importance of studying inherited hematological disorders in ancient Anatolian populations. AB - Before analysis of DNA from ancient remains was possible, anthropologists studied evolution and migration patterns using data obtained from population genetic studies on modern populations combined with data obtained from morphological evaluations of ancient remains. Currently, DNA analysis of ancient populations is making a valuable contribution to these efforts. Researchers that perform ancient DNA analysis prefer to study polymorphisms on the Y chromosome or mitochondrial DNA because the results are easier to statistically evaluate. To evaluate polymorphisms on diploid genomes, which are more informative, only mutations that have been extensively examined in modern populations should be chosen. The most extensively evaluated mutations are those related to prevalent inherited disorders. As such, beta-thalassemia, sickle cell anemia, FVL mutation of globin and the factor V genes are good candidates for DNA studies in ancient populations. These mutations are common in Anatolia, host to many civilizations since the Paleolithic period. This history makes Anatolia a good place for conducting research that could enhance our understanding of human evolution and migration patterns. PMID- 27264581 TI - Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey. AB - OBJECTIVE: The prevalence of beta-thalassemia in Sanliurfa province, Turkey is reported to be 2.6%-3.7%, whereas nation-wide the frequency of beta-thalassemia is 2%. This study aimed to identify the most frequent beta-thalassemia mutations in Sanliurfa province. METHODS: In total, 22 mutations were investigated in 115 pediatric patients with beta-thalassemia using a commercially available reverse dot blot platform. RESULTS: The study included 60 male and 55 female patients with a mean age of 7.3+/-4.6 years (range: 1-17 years). In total, 76% of the patients had consanguineous parents. In all, 16 different mutations were observed in the 115 patients. IVS-1-110 (G-A) (29.1%), IVS-1-1 (G-A) (13.9%), codon 39 (C>T) (10.4%), and codon 8 (-AA) (9.1%) accounted for 62.5% of all the beta thalassemia mutations, and 6% of the patients had 2 different thalassemia mutations. According to the present results, IVS-1-110 (G>A) was the most frequent mutation observed in the patients from Sanliurfa province, as in other geographical regions of Turkey. In addition, the following 34 compound heterozygote mutant alleles were observed; IVS-1-1 (G>A)/IVS 2.848 (n=4), codon 39 (C>T)/codon 8 (-AA) (n=2), codon 6 (-A)/IVS 1.5 (G>C) (n=2), IVS-1-110 (G>A)/IVS-1-1 (G>A) (n=2), IVS-1-110 (G>A)/codon 8 (-AA) (n=1), IVS-1-110 (G>A)/codon 39 (C>T) (n=1), IVS-1-110 (G>A)/IVS-1-6 (T>C) (n=1), IVS-1-110 (G>A)/IVS-1-5 (G>C) (n=1), IVS-1-110 (G>A]/codon 8/9 (+G) (n=1), IVS-1-1 (G>A)/codon 39 (C>T) (n=1), and codon 8 (-AA)/IVS-1-5 (G>C) (n=1). The following beta-globin gene promoter mutations were not observed; -101 (C>T), -87(C>T), -30 (T>A), codon 15 (TTG>TGA), codon 27 (G>T) Knossos, and IVS-1-116 (G>C). In all, 5 of the 115 patients (4.3%) had an unidentified mutation. CONCLUSION: The present results illustrate the heterogeneity of beta-thalassemia mutations in Sanliurfa Province. The present findings may be of value for genetic counseling, and premarital and prenatal diagnosis in Sanliurfa province. PMID- 27264582 TI - Tracing the footsteps of IVS-I-130 G-C mutation of the human hemoglobin beta globin gene: From Sanliurfa to Askeriye, Burdur, Turkey. PMID- 27264583 TI - Antifungal prophylaxis in stem cell transplantation centers in Turkey. AB - OBJECTIVE: This study aimed to determine the current state of antifungal prophylaxis in Turkish stem cell transplantation (SCT) centers. METHODS: he were 38 active stem cell transplantation centers in Turkey, 28 of which were registered with the European Group for Blood and Marrow Transplantation (EBMT). Survey questionnaires were sent to the 28 EBMT centers in an effort to collect data on antifungal prophylaxis in different settings. In all, 24 of the centers completed the survey; 1 of the 24 centers was excluded from the study, as it was under construction at the time and was not performing transplantation. RESULTS: In all, 15 (65%) of the 23 centers were adult SCT centers, 7 (31%) were pediatric SCT centers, and 1 center treated both adult and pediatric patients. All centers (23/23) performed both allogeneic and autologous transplants, 20 centers performed non-myeloablative transplants, 8 performed cord blood transplants, and 7 performed unrelated transplants. Primary antifungal prophylaxis was used at all 23 centers during allogeneic transplants, whereas 18 of the 23 centers used it during every autologous transplant and 2 of the 23 centers used it during autologous transplants on a per case basis. The most common drug used for prophylaxis was fluconazole (F) (21/23), followed by itraconazole (I) (3/23), amphotericin-B (2/23), and posaconazole (1/23). Among the 23 centers, 3 reported that for allogenic transplants they changed the antifungal prophylactic in cases of graft versus host disease (GVHD), and 12 of the 23 centers reported that they changed the antifungal prophylactic in case of nearby construction. All 23 centers performed secondary prophylaxis. CONCLUSION: Antifungal prophylaxis for hematopoetic SCT patients was the standard protocol in the 23 centers included in the study, usually with such azoles as F. The introduction of posaconazole in Turkey and the potential approval of voriconazole for antifungal prophylaxis will eventually alter prophylaxis practice in Turkey, which we plan to assess in the future. PMID- 27264584 TI - The effects of Ankaferd(r) Blood Stopper on transcription factors in HUVEC and the erythrocyte protein profile. AB - OBJECTIVE: Ankaferd(r) Blood Stopper (ABS) is an herbal extract that has historically been used as a hemostatic agent in traditional Turkish medicine. ABS is comprised of a standardized herbal mixture of T. vulgaris, G. glabra, V. vinifera, A. officinarum, and U. dioica. ABS's basic mechanism of action is the formation of an encapsulated protein web, which represents the focal point for vital erythrocyte masses. The hemostatic effects of ABS have been observed in vitro and in vivo. ABS was registered as a hemostatic agent for external hemorrhages and dental bleeding following phase I randomized, double-blind crossover placebo-controlled clinical research, and safety and efficacy reports. In terms of the potential use of ABS, transcription factors may be novel factors that play a role in the hemostatic and other pleiotropic effects of ABS. METHODS: Hence, the present study aimed to investigate the effects of ABS on endothelium, and possible transcription factor changes in HUVEC (human umbilical vein endothelial cells) and the erythrocyte membrane profile. ABS (5 MUL and 50 MUL) was administered to HUVEC (in 75 cm2; ~75% fullness) for 5 min and 15 min. RESULTS: ABS caused significant increases in the level of activation of the following transcription factors; AP2, AR, CRE/ATF1, CREB, E2F1-5, E2F6, EGR, GATA, HNF-1, ISRE, Myc-Max, NF-1, NFkB, p53, PPAR, SMAD 2/3, SP1, TRE/AP1, and YY1. Following erythrocyte membrane isolation, protein complexes were undissolved, but denatured. The protein complex formed was resistant to heat and detergent. Trypsin and sonication were used in order to break this complex; the complex dissolved and erythrocyte membrane proteins were released in SDS-PAGE. CONCLUSION: ABS established a very fast and solid protein web, and increased the level of transcription factor activation. Therefore the cellular effects of ABS could be related to different intracellular biological pathways. PMID- 27264585 TI - Long-term outcome in children with nutritional vitamin B12 deficiency. AB - OBJECTIVE: Vitamin B12 deficiency is frequently observed in developing countries. Herein we report the long-term clinical and laboratory outcomes in 45 children presented with various symptoms of vitamin B12 deficiency. METHODS: Symptoms and physical findings, and percentiles for weight, height, and head circumference at presentation were recorded. The educational level of the patients' mothers, vitamin B12 deficiency-related diseases and family income data were collected. Complete blood count, serum vitamin B12, folate, iron, iron binding capacity and ferritin, and plasma homocysteine levels were recorded measured at presentation. The patients were treated with vitamin B12, as follows: 1 mg/d IM for 1 week, followed by 1 mg IM QWK for 2 weeks, and then monthly 1mg injections. Patients were neurologically and hematologically re-evaluated after treatment. The visual evoked potential (VEP) test was used to examine the integrity and function of the visual pathway. Brainstem evoked potential (BAEP) responses were used to analyze auditory function. Neuromotor development was assessed using Denver II Development Screening Test. RESULTS: The mean age of 20 male and 25 female patients was 5.6+/-5.9 years (range: 1.4 months-17 years). The most common symptoms at presentation were weakness, failure to thrive, and hematologic manifestations (pallor, petechiae, ecchymosis). Abnormal neurologic findings at presentation were observed in 20% of the patients, and were more commonly observed in those <2 years. VEP, BAEP, and Denver II Development tests were performed in 66% of the patients one year after vitamin B12 replacement was started. VEP and BAEP interval prolongation was observed in 37% and 17% of the cases, respectively. Denver II Development Test results showed developmental delay in 20% of the patients tested. CONCLUSION: All the patients achieved full hematologic recovery within 1 month of treatment onset. Neurological symptoms resolved following B12 administration; however, during long-term follow-up ranged from 17% to 37% of the tested patients had persistent VEP; BERA, and Denver II abnormalities. Neurological symptoms resolved following B12 administration; however, during long-term followup 33% of the patients had persistent VEP, BERA, and Denver II abnormalities. As such, clinicians should continue to follow-up such patients even after hematologic and clinical improvement are obtained in order to assess their neurologic status. PMID- 27264586 TI - Clinical investigation of oral findings in inherited disorders of platelet function. AB - OBJECTIVE: Bleeding disorders are a very important health problem due to the associated high risk of hemorrhage during dental procedures. The present study aimed to investigate oral manifestations of inherited disorders of platelet function (IDPF). METHODS: The study included 20 IDPF patients (mean age: 31.90+/ 10.71 years) and 40 healthy controls (mean age: 31.63+/-9.07 years). Tooth brushing habits, level of education, and clinical index scores (Simplified Oral Hygiene Index [OHI-S], Decayed Missing Filled Teeth Index [DMFT] index, probing depth [PD] index, Gingival Bleeding Index [GBI], and Community Periodontal Index [CPI]) were recorded. RESULTS: There weren't any significant differences between the 2 groups with respect to tooth brushing habit, level of education level, OHI S, DMFT index, or CPI (p>0.05), whereas significant differences in PD index and GBI were observed between the groups (p<0.05). CONCLUSION: The present study's findings show that IDPF has a negative effect on periodontal tissues. PMID- 27264587 TI - Factor V G1691A (Leiden) is a major etiological factor in Egyptian Budd-Chiari syndrome patients. AB - OBJECTIVE: Budd-Chiari syndrome is a multifactorial disease in which several prothrombotic disorders may predispose patients to the development of thrombosis at this uncommon location (hepatic veins). The aim of this study was to determine the prevalence and characteristics of inherited thrombophilia in Egyptian Budd Chiari syndrome patients. METHODS: The study included 47 Budd-Chiari syndrome patients (20 children and 27 adults). Genotyping of Factor V G1691A (Leiden), prothrombin G20210A (PT), and methylenetetrahydrofolate reductase C677T were performed using real-time PCR and fluorescence melting curve detection analysis. RESULTS: Factor V Leiden was observed in 29 patients (61.7%). It is the only factor that caused Budd-Chiari syndrome in 18 of the patients and in 5 of the patients with inferior vena cava involvement. Myeloproliferative disease was noted in 12 (25.5%) patients, antiphospholipid syndrome in 5 (10.6%), and Behcet's disease in 3 (6.4%). Interestingly, 3 of the children with Budd-Chiari syndrome had lipid storage disease. CONCLUSION: Factor V Leiden was a major etiological factor in Egyptian Budd-Chiari syndrome patients, which may have been related to the high frequency of this mutation in the study region. Factor V Leiden was also a strong thrombophilic factor and the leading cause of inferior vena cava thrombosis in these patients. Lipid storage disease should be included as a risk factor for Budd-Chiari syndrome. PMID- 27264588 TI - Factor V G1691A (Leiden) and prothrombiG20210A gene mutation status, and thrombosis in patients with chronic myeloproliferative disorders. AB - OBJECTIVE: The aim of this study was to examine Factor V G1691A (Leiden) (FVL) and prothrombin G20210A (PT) gene mutation status, and their relationship with thrombosis in patients with chronic myeloproliferative disorders (CMPDs). METHODS: The study included 160 patients with a CMPD that were regularly followed up between 1993 and 2009. FVL and PT mutation status was established based on blood samples analyzed via PCR using specific primers. RESULTS: The frequency of FVL and PT mutation was 12.5% and 4.4%, respectively. In total, 27 episodes of thrombosis occurred in 24 (15%) of the patients, and there wasn't an association between the observed thrombotic events, and FVL or PT mutations. Hepatic vein thrombosis was noted in 3 patients that had FVL mutation, of which 1 also had PT mutation. CONCLUSION: We did not observe a relationship between thrombosis, and FVL or PT mutations in CMPD patients; however, 3 of the patients that had hepatic vein thrombosis also had FVL mutation. Larger studies are needed to more clearly determine if all CMPD patients with hepatic vein thrombosis need be investigated for FVL and PT mutation. PMID- 27264589 TI - Plasmacytoid dendritic cell tumor: A case report. AB - A 62-year-old man presented with a painless eruption on his arms and trunk. Physical examination showed 2 well-demarcated erythematous plaques on the anterior trunk and 6 purple-red papules on the back and upper extremities. Blood chemistry and computed tomography results were normal. Herein we describe a patient with plasmacytoid dendritic cell neoplasm in the absence of systemic symptoms. PMID- 27264590 TI - Involuntary movement in infants during vitamin B12 treatment. AB - Megaloblastic anemia is rare in infants and is generally due to vitamin B12 (cobalamin) deficiency in the mother. Neurologic symptoms of vitamin B12 deficiency include irritability, failure to thrive, hypotonia, and developmental regression/delay. Herein we present 2 infants with vitamin B12 that developed movement disorder 5 d after initiation of vitamin B12 treatment. Symptoms included tremor and myoclonus, involving in particular the face, tongue, and hands. Clinical findings in infants associated with vitamin B12 deficiency vary, and temporary involuntary movement can be observed during vitamin B12 therapy. PMID- 27264591 TI - Two rare hemoglobin variants in the Cukurova Region of Turkey: Hb E-Saskatoon and Hb G-Coushatta. AB - Hb E-Saskatoon and Hb G-Coushatta are rare hemoglobin variants that are not a health problem. Herein we present a Turkish woman that was diagnosed as homozygous Hb E-Saskatoon (only the second such case reported from Turkey) and a Turkish boy diagnosed as heterozygote Hb E-Saskatoon. Additionally, 2 Turkish sisters diagnosed as heterozygote Hb G-Coushatta are presented. PMID- 27264592 TI - Malignant lymphoma associated with Behcet's disease: A report of 2 cases. AB - Herein we report 2 cases of malignant lymphoma associated with Behcet's disease. Case 1, a 53-yearold man, was diagnosed as Behcet's disease at the age of 26 years, and was treated with cyclophosphamide and prednisolone. At 45 years of age, bilateral enlarged lymph nodes were observed in the patient's neck. Evaluation of a lymph node biopsy specimen showed Hodgkin's disease and chemotherapy was administered. Due to disease recurrence 7 years later, chemotherapy and radiotherapy were administered. Case 2, a 67-year-old male, was diagnosed as Behcet's disease at age 44 years and began colchicine treatment. At 60 years of age a mass in his left tonsillar fossa was noted. Evaluation of a left tonsil biopsy specimen showed malignant lymphoma. Radiotherapy and chemotherapy were subsequently administered. At the time this report was written both patients were disease-free. Malignant lymphoma associated with Behcet's disease is rare-only 17 cases have been published. In addition to the presented cases, the literature regarding malignant lymphoma associated with Behcet's disease is reviewed. PMID- 27264593 TI - A survey of hematologists on compulsory health service in Turkey. PMID- 27264594 TI - Unusual presentation of adrenal lymphoma observed with PET-CT. PMID- 27264595 TI - Scrotal abscess extending into the inguinal canal: A rare complication of multipl myeloma. PMID- 27264596 TI - Double heterozygosity of the thalassemic mutations term. Cd +6 C->G and IVS-I-110 in a Greek woman: A case presentation. PMID- 27264597 TI - First report from Turkey of a rare frameshift mutation [codons 9/10 (+T)] in the beta-globin gene. PMID- 27264598 TI - First observation of hemoglobin Crete [Beta129(H7) Ala>Pro] in the Turkish population. PMID- 27264599 TI - The frequency of Factor V G1691A (Leiden) mutation in Iraqi Turks. PMID- 27264600 TI - Acute thrombotic complication of essential thrombocythemia. PMID- 27264601 TI - The frequency of factor V G1691A (Leiden) mutation in the healthy Kazakh population. PMID- 27264602 TI - A novel 110-bp insertion in a patient with homocysteinuria. PMID- 27264603 TI - Overwhelming bone marrow Leishmaniasis. PMID- 27264604 TI - The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites. AB - In the mammalian intestine, crypts of Leiberkuhn house intestinal epithelial stem/progenitor cells at their base. The mammalian intestine also harbors a diverse array of microbial metabolite compounds that potentially modulate stem/progenitor cell activity. Unbiased screening identified butyrate, a prominent bacterial metabolite, as a potent inhibitor of intestinal stem/progenitor proliferation at physiologic concentrations. During homeostasis, differentiated colonocytes metabolized butyrate likely preventing it from reaching proliferating epithelial stem/progenitor cells within the crypt. Exposure of stem/progenitor cells in vivo to butyrate through either mucosal injury or application to a naturally crypt-less host organism led to inhibition of proliferation and delayed wound repair. The mechanism of butyrate action depended on the transcription factor Foxo3. Our findings indicate that mammalian crypt architecture protects stem/progenitor cell proliferation in part through a metabolic barrier formed by differentiated colonocytes that consume butyrate and stimulate future studies on the interplay of host anatomy and microbiome metabolism. PMID- 27264605 TI - Morphomechanical Innovation Drives Explosive Seed Dispersal. AB - How mechanical and biological processes are coordinated across cells, tissues, and organs to produce complex traits is a key question in biology. Cardamine hirsuta, a relative of Arabidopsis thaliana, uses an explosive mechanism to disperse its seeds. We show that this trait evolved through morphomechanical innovations at different spatial scales. At the organ scale, tension within the fruit wall generates the elastic energy required for explosion. This tension is produced by differential contraction of fruit wall tissues through an active mechanism involving turgor pressure, cell geometry, and wall properties of the epidermis. Explosive release of this tension is controlled at the cellular scale by asymmetric lignin deposition within endocarp b cells-a striking pattern that is strictly associated with explosive pod shatter across the Brassicaceae plant family. By bridging these different scales, we present an integrated mechanism for explosive seed dispersal that links evolutionary novelty with complex trait innovation. VIDEO ABSTRACT. PMID- 27264606 TI - Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins. AB - Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation. PMID- 27264607 TI - Subcellular Imaging of Voltage and Calcium Signals Reveals Neural Processing In Vivo. AB - A mechanistic understanding of neural computation requires determining how information is processed as it passes through neurons and across synapses. However, it has been challenging to measure membrane potential changes in axons and dendrites in vivo. We use in vivo, two-photon imaging of novel genetically encoded voltage indicators, as well as calcium imaging, to measure sensory stimulus-evoked signals in the Drosophila visual system with subcellular resolution. Across synapses, we find major transformations in the kinetics, amplitude, and sign of voltage responses to light. We also describe distinct relationships between voltage and calcium signals in different neuronal compartments, a substrate for local computation. Finally, we demonstrate that ON and OFF selectivity, a key feature of visual processing across species, emerges through the transformation of membrane potential into intracellular calcium concentration. By imaging voltage and calcium signals to map information flow with subcellular resolution, we illuminate where and how critical computations arise. PMID- 27264608 TI - Relatives' Presence During Cardiopulmonary Resuscitation. AB - BACKGROUND: The question of whether or not to allow family to be present during resuscitation is relevant to everyday professional health care assistance, but it remains largely unexplored in the medical literature. OBJECTIVES: We conducted an online survey with the aim of increasing our knowledge and understanding of this issue. METHODS: This is a cross-sectional, multicenter, descriptive, national, and international study using a web-based, voluntary survey. The survey was designed and distributed through a medical website in Spanish, targeting physicians who frequently deal with critical patients. RESULTS: A total of 1,286 Argentine physicians and 1,848 physicians from other countries responded to this voluntary survey. Of Argentine respondents, 15.8% (203) treat only children, 68.2% (877) treat adults, and 16% (206) treat patients of any age. The survey found that 23% (296) of Argentine and 20% of other respondents favor the presence of family members during cardiopulmonary resuscitation (p = 0.03). This practice was more common among physicians treating pediatric and neonatal patients than among those who treat adults. The most commonly reported reason (21.8%) for avoiding the presence of relatives was concerns that physicians, communications, and medical practices might be misunderstood or misinterpreted. CONCLUSIONS: Avoiding relatives' presence while performing cardiopulmonary resuscitation is the most frequent choice made by the surveyed physicians who treat critical Argentine patients. The main causes for discouraging family presence during cardiopulmonary resuscitation or other critical procedures include the following: risk of misinterpretation of the physician's actions and/or words; risk of a relative's decompensation; uncertainty about possible reactions; and interpretation of the relative's presence as negative. PMID- 27264610 TI - Equid herpesvirus 1 and rhodococcus equi coinfection in a foal with bronchointerstitial pneumonia. AB - A 2-month-old foal with septic shock and severe respiratory distress was referred to the Veterinary Teaching Hospital. Due to poor prognosis, the foal was euthanized. Histopathology showed lesions suggestive of Rhodococcus equi infection associated with a diffuse interstitial infiltrate of foamy macrophages and syncytial cells presenting large acidophilic intranuclear inclusion bodies, fibrin exudates and hyaline membranes. Bacteriological examination from lung and respiratory exudates confirmed R. equi infection, whilst immunohistochemistry and PCR yielded a positive result for Equid herpesvirus type 1 (EHV-1). Several etiologies have been proposed for bronchointerstitial pneumonia in foals, although a multifactorial origin for this lesional pattern could be possible. This work is the first one describing a combined EHV-1 and R. equi infection in a foal affected with bronchointerstitial pneumonia. PMID- 27264611 TI - Association between age, breed and sex in relation to urinary disorders in insured cats in Japan during fiscal year 2012. AB - Data from 48,187 cats insured between April 2012 and March 2013 were analyzed using logistic regression analysis to determine the association of age, breed and sex with the occurrence of urinary disorders. The overall annual prevalence of urinary disorders was 12.2%. Using crossbreeds as the reference breed, Abyssinian cats had the highest odds of having urinary disorders with a ratio of 1.40 (95% confidence interval: 1.20-1.63), followed by Norwegian Forest Cats and Somalis. Male cats had higher odds of having urinary disorders with a ratio of 1.27 (1.20 1.35) over female cats. Older cats had higher odds of having urinary disorders than young cats. PMID- 27264609 TI - PolyMetformin combines carrier and anticancer activities for in vivo siRNA delivery. AB - Metformin, a widely implemented anti-diabetic drug, exhibits potent anticancer efficacies. Herein a polymeric construction of Metformin, PolyMetformin (PolyMet) is successfully synthesized through conjugation of linear polyethylenimine (PEI) with dicyandiamide. The delocalization of cationic charges in the biguanide groups of PolyMet reduces the toxicity of PEI both in vitro and in vivo. Furthermore, the polycationic properties of PolyMet permits capture of siRNA into a core-membrane structured lipid-polycation-hyaluronic acid (LPH) nanoparticle for systemic gene delivery. Advances herein permit LPH-PolyMet nanoparticles to facilitate VEGF siRNA delivery for VEGF knockdown in a human lung cancer xenograft, leading to enhanced tumour suppressive efficacy. Even in the absence of RNAi, LPH-PolyMet nanoparticles act similarly to Metformin and induce antitumour efficacy through activation of the AMPK and inhibition of the mTOR. In essence, PolyMet successfully combines the intrinsic anticancer efficacy of Metformin with the capacity to carry siRNA to enhance the therapeutic activity of an anticancer gene therapy. PMID- 27264612 TI - Plasma Levels of Alanine Aminotransferase in the First Trimester Identify High Risk Chinese Women for Gestational Diabetes. AB - Alanine aminotransferase (ALT) predicts type 2 diabetes but it is uncertain whether it also predicts gestational diabetes mellitus (GDM). We recruited 17359 Chinese women with ALT measured in their first trimester. At 24-28 weeks of gestation, all women underwent a 50-gram 1-hour glucose challenge test (GCT) followed by a 75-gram 2-hour oral glucose tolerance test if GCT result was >=7.8 mmol/L. Restricted cubic spline analysis was used to examine full-range risk associations of ALT levels with GDM. Relative excess risk due to interaction, attributable proportion due to interaction and synergy index were used to estimate additive interaction between high ALT and overweight/obesity for GDM. Finally, 1332 (7.7%) women had GDM. ALT levels were positively associated with GDM risk without a clear threshold. Using ALT levels <22 U/L as the referent, the middle ALT levels (>=22 to <40 U/L) [odds ratio (OR) (95% confidence intervals): 1.41(1.21-1.65)] and high ALT levels (>=40 U/L) [1.62 (1.31-2.00)] were associated with increased GDM risk. Maternal overweight/obesity greatly enhanced the OR of ALT >=22 U/L from 1.44 (1.23-1.69) to 3.46 (2.79-4.29) with significant additive interactions. In conclusion, elevated ALT levels in the first trimester even within normal range predicted GDM risk, further enhanced by overweight/obesity. PMID- 27264614 TI - In vitro effects of increased temperature and decreased pH on blood oxygen affinity of 10 fish species of the Amazon. AB - Blood-O2 affinities (P50 ) were measured over a physiologically relevant pH range at 31 (highest temperature average of Rio Negro over the last 8 years), 33 and 35 degrees C for 10 species of the Rio Negro, aiming to test the acute effects of temperature foreseen by the IPCC (Intergovernmental Panel on Climate Change) for coming years. The animals were collected during an expedition to the Anavilhanas Islands of the Rio Negro, 110 km upstream from Manaus (2 degrees 23' 41" S; 60 degrees 55' 14" W). Hoplias malabaricus showed higher blood-O2 sensitivity to pH changes (Bohr effect, Phi = Deltalog10 P50 DeltapH(-1) ) at both 31 degrees C (Phi = -0.44) and 35 degrees C (Phi = -0.26) compared to Osteoglossum bicirrhosum (Phi = -0.54 at 31 degrees C and Phi = -0.58 at 35 degrees C), but lower P50 under most conditions, and a greater sensitivity of P50 to temperature. Two out of the 10 analysed species had significant increases of P50 (lower blood O2 affinity) at the highest temperature throughout the pH range tested. For all other species, a minor increase of P50 over the assay-tested temperatures was observed, although all presented a normal Bohr effect. Overall, a diversity of intensities of pH and temperature effects on blood-O2 affinities was observed, which seems to be connected to the biological characteristics of the analysed species. Thermal disturbances in their habitats, likely to occur due to the global warming, would impair blood-O2 binding and unloading in some of the analysed fish species. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27264613 TI - Identification and characterization of DcUCGalT1, a galactosyltransferase responsible for anthocyanin galactosylation in purple carrot (Daucus carota L.) taproots. AB - Purple carrots (Daucus carota ssp. sativus var. atrorubens Alef.) accumulate large amounts of cyanidin-based anthocyanins in their taproots. Cyanidin can be glycosylated with galactose, xylose, and glucose in sequence by glycosyltransferases resulting in cyanidin 3-xylosyl (glucosyl) galactosides in purple carrots. The first step in the glycosylation of cyanidin is catalysis by UDP-galactose: cyanidin galactosyltransferase (UCGalT) transferring the galactosyl moiety from UDP-galactose to cyanidin. In the present study, a gene from 'Deep purple' carrot, DcUCGalT1, was cloned and heterologously expressed in E. coli BL21 (DE3). The recombinant DcUCGalT1 galactosylated cyanidin to produce cyanidin-3-O-galactoside and showed optimal activity for cyanidin at 30 degrees C and pH 8.6. It showed lower galactosylation activity for peonidin, pelargonidin, kaempferol and quercetin. It accepted only UDP-galactose as a glycosyl donor when cyanidin was used as an aglycone. The expression level of DcUCGalT1 was positively correlated with anthocyanin biosynthesis in carrots. The enzyme extractions from 'Deep purple' exhibited galactosylation activity for cyanidin, peonidin and pelargonidin, while those from 'Kuroda' (a non-purple cultivar) did not. PMID- 27264615 TI - [Age discrimination. Point of view of the professionals]. AB - INTRODUCTION: It is generally believed that legislation is an essential resource in the prevention of discriminatory behaviour against older people. This study first examines the Spanish legislation for potential age discrimination and then uses the C-EVE-D questionnaire to ask professionals in social work and health care settings the extent to what certain ageist behaviours described in the questionnaire are observed in practice. METHODS: The field study was carried out with professionals in geriatrics and gerontology, who are members of Spanish Society for Geriatrics and Gerontology (SEGG). The EVE discrimination questionnaire consists of 28 items which investigate the existence of age discrimination in medical and social care contexts. RESULTS: A total of 174 people (63% women; mean age: 45.6 years) took part in the study, with a mean professional experience of 17.2 years. Doctors made up 59% of the sample, psychologists 19%, with the rest coming from other professions. The first 20 discrimination items of the EVE-D questionnaire were significantly positively reported by more than 60% of the sample. CONCLUSIONS: Although Spanish legislation, from the constitution down to the rules that govern social and health care settings, clearly prohibits any kind of discrimination with regard to age, our results show that Spanish professionals most closely involved in the care of older people perceive both direct and indirect age discrimination. Furthermore, evidence was found of prejudice in the treatment of older people as a phenomenon in day-to-day health and social services care, both when analysing medical cases and, to a greater extent, cases of a more general nature and/or relating to co-existence. PMID- 27264616 TI - [Health status of centenarians in a general hospital in Lima-Peru]. PMID- 27264617 TI - [Anticholinergic burden and delirium in elderly patients during acute hospital admission]. AB - BACKGROUND: The use of anticholinergic drugs in the elderly has been associated to an increased frequency of delirium. There are different scales for estimating the anticholinergic burden, such as the Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Anticholinergic Cognitive Burden (ACB). The aim of the study is to establish the relationship between anticholinergic burden measured by ADS, ARS, and ACB scales and incident or prevalent delirium. METHODS: An ambispective observational study was conducted for 76 days in the acute geriatric unit of a tertiary hospital. All patients over 80 years-old were included, except re-admissions or those subjected to palliative care. The data collected included sex, age, chronic medication and any recent changes, recent drugs prescribed prior to an episode of delirium, chronic kidney disease, diabetes mellitus, dementia, visual and auditory impairment, and their combination as sensory impairment, previous falls, stroke, brain tumour, and incident and prevalent delirium. RESULTS: A total of 72 patients were included. Incident delirium was detected in 8.1% of the patients, and prevalent delirium in 40.9%. A statistically significant association was established between anticholinergic drugs and the incident delirium measured by the ARS scale (P=.017). None of the scales was able to establish a significant association with prevalent delirium. CONCLUSION: The ARS scale was related to new episodes of delirium. All scales were insufficient when it came to establishing an association with prevalent delirium. PMID- 27264618 TI - Neurocognitive Correlates of Successful Treatment of PTSD in Female Veterans. AB - BACKGROUND: The influence of psychotherapy on neurocognition in post-traumatic stress disorder (PTSD) has not been examined methodically. This is despite evidence that pre-treatment learning and memory has been associated with treatment success and that executive function theories emphasize weak executive functions (especially inhibition/switching) are associated with PTSD. OBJECTIVES: To determine (1) if higher pre-treatment learning/memory, inhibition/switching, or both predict treatment success; and (2) if treatment success is associated with specific improvement in inhibition/switching and not learning/memory or working memory, another aspect of executive function. METHODS: Pre-treatment neurocognition and neurocognitive changes (inhibition/switching, learning/memory, working memory) were examined in female veterans with PTSD. They were evaluated before and after 16-weeks of group psychotherapy for PTSD that included three counterbalanced modules (cognitive restructuring therapy, exposure therapy, skills training) with fidelity checks for therapist adherence. RESULTS: Only pre treatment learning/memory predicted better treatment outcome. Treatment success was associated with improvement in inhibition/switching only, even after controlling for mild traumatic brain injury, and changes in depressive symptoms, working memory, and learning/memory. CONCLUSIONS: Our finding that learning/memory predicted treatment success is consistent with previous studies. We extended these studies by showing that the effect was restricted to learning/memory, which is contrary to the executive function theory of PTSD. In contrast, the fact that only inhibition/switching significantly improved with better treatment success is consistent with its potential importance in maintaining PTSD symptoms. Future research should determine whether inhibition/switching abilities are a risk for development and maintenance of PTSD or whether such abilities have a broader reciprocal relationship with PTSD symptom change. (JINS, 2016, 22, 643-651). PMID- 27264619 TI - Contribution of limb momentum to power transfer in athletic wheelchair pushing. AB - Pushing capacity is a key parameter in athletic racing wheelchair performance. This study estimated the potential contribution of upper limb momentum to pushing. The question is relevant since it may affect the training strategy adopted by an athlete. A muscle-free Lagrangian dynamic model of the upper limb segments was developed and theoretical predictions of power transfer to the wheelchair were computed during the push phase. Results show that limb momentum capacity for pushing can be in the order of 40J per push cycle at 10m/s, but it varies with the specific pushing range chosen by the athlete. Although use of momentum could certainly help an athlete improve performance, quantifying the actual contribution of limb momentum to pushing is not trivial. A preliminary experimental investigation on an ergometer, along with a simplified model of the upper limb, suggests that momentum is not the sole contributor to power transfer to a wheelchair. Muscles substantially contribute to pushing, even at high speeds. Moreover, an optimal pushing range is challenging to find since it most likely differs if an athlete chooses a limb momentum pushing strategy versus a muscular exertion pushing strategy, or both at the same time. The study emphasizes the importance of controlling pushing range, although one should optimize it while also taking the dynamics of the recovery period into account. PMID- 27264622 TI - The Relationship of Haemostatic System to the Vessel Wall, Thromboembolism, Atherosclerosis from Pathogenesis and Laboratory Standpoints. PMID- 27264620 TI - Does plastic suture deformation induce gapping after tendon repair? A biomechanical comparison of different suture materials. AB - Plastic deformation of sutures creates an irreversible extension during load. To test our hypothesis that such plastic deformation causes gap formation after tendon repair, we determined the plasticity of five different suture materials commonly used in tendon surgery. Prolene, Polydioxanone (PDS), Ethibond, Vicryl, and FiberWire sutures were biomechanically tested to determine their offset yield strength, initial extension, creep, relaxed elongation, peak-to-peak displacement, stiffness, and maximum tensile strength under static, constant, and cyclic loading. In addition, 35 porcine hindlimb tendons were used to evaluate gap formation and the biomechanical behavior of the suture materials after tendon repair. Prolene had a low offset yield strength and high initial extensions at 30, 60, and 90N combined with relatively large creep, relaxed elongation, and peak-to-peak displacement. Aside from the low maximum tensile strength and stiffness, these parameters indicate an early plastic deformation during loading. The material properties of PDS were generally better for suturing than those of Prolene, but no difference was found in offset yield strength or initial extension. In contrast to the monofilament materials Prolene and PDS, the braided Ethibond, Vicryl, and FiberWire materials showed significantly less plastic deformation. The lowest amount of plastic deformation was found in the FiberWire and the results for Ethibond and Vicryl were equal. Gap formation occurred at the lowest tension force in the Prolene group, but only FiberWire required a significantly larger tension force to produce gapping at the repair site, indicating a higher resistance to gap formation. The results of this study show that plastic deformation occurs at a lower tension force in the monofilament sutures Prolene and PDS than in the braided materials Ethibond, Vicryl, and FiberWire. After tendon repair, FiberWire likely prevents gap formation, whereas Prolene induces gapping through low-tension plastic deformation. Therefore, plastic deformation should be considered when selecting suture materials for tendon repair surgery. PMID- 27264623 TI - Does von Willebrand Factor Have an Effect on the Occurrence of the Diabetic Complications? AB - It has been reported that von Willebrand factor (vWf) plays a role in the development of complications of diabetes mellitus. The relationships between vWf and polyneuropathy, nephropathy, and retinopathy were investigated in the patients with type 2 diabetes mellitus. 58 patients with type 2 diabetes mellitus (22 men and 36 women, mean age 54 +/- 9 ) and 30 healthy nondiabetic controls (12 men and 18 women, mean age 40 +/- 11) were admitted to this study. They were examined by an internist, a neurologist and an ophtalmologist for complications of diabetes mellitus. Electromyography was performed to all the patients. The mean vWf levels of the patients and control group were 1.48 +/- 0.55 and 1.25 +/- 0.32 IU/mL respectively. There was no significant difference between the two groups (p= 0.146). Diabetic retinopathy in 18 patients (31%), polyneuropathy in 20 patients (34.5%), trap neuropathy in 5 patients (8.6%), microalbuminuria in 9 patients (15.5%), macroalbuminuria in 2 patients (3.5%) and normoalbuminuria in 47 patients (81%) were detected. The difference between vWf levels of the patients with retinopathy and without retinopathy were not statistically significant (p= 0.913). There was no significant difference between patients with polyneuropathy and without polyneuropathy group (p= 0.737). There was also no difference between trap neuropathy and without trap neuropathy (p= 0.431), and between polyneuropathy and trap neuropathy (p= 0.246) patient subgroups. The vWf levels in normoalbuminuric, microalbuminuric and macroalbuminuric patient groups were not different (p values: 0.526, 0.392 and 0.759 respectively). vWf levels between patients with complications of diabetes mellitus and control group were not different (p> 0.05). There was not a significant correlation between the vWf level and body mass index, serum glucose, triglycerides, total cholesterol, HDL C, LDL-C, VLDL-C, platelet counts, fibrinogen levels, prothrombin and activated thromboplastin times in 33 patients with any complication of diabetes mellitus (p> 0.05). We conclude that, vWf has not an effect in the development of complications in patients with diabetes mellitus. PMID- 27264624 TI - Tumour Necrosis Factor-Alpha Gene Polymorphism (-308 G-A) in Turkish Pediatric Thrombosis Patients. AB - Tumour necrosis factor-alpha (TNF-a) plays an important role in clot formation by activating platelets, monocytes and endothelial cells and inducing procoagulant substances such as negatively charged phospolipids or tissue factor. There is a genetically controlled inter-individual variation of TNF-a production. Carrying TNF2 allele could have a slight protective effect against the occurence of stroke in Sickle Cell Disease patients. We aimed to study this polymorphic site in Turkish children with the diagnosis of thrombosis. PMID- 27264625 TI - Polycythemia Vera Presenting with Fulminant Hepatic Failure Due to Acute Budd Chiari Syndrome: Case Report. AB - We describe a 38 year-old woman with polycythemia vera who presented with fulminant hepatic failure due to acute Budd-Chiari syndrome. She had a history of abdominal pain and distention for 4 days. Laboratory and clinical findings showed fulminant hepatic failure due to acute Budd-Chiari syndrome. Diagnosis was confirmed with abdominal ultrasonography and doppler ultrasonography showing ascites, hepatomegaly, portal hypertension and total occlusion of hepatic veins. Complete blood count and other clinical findings were compatible with polycythemia vera. The patient was successfully treated with urgent administration of continuous heparin infusion, repeated phlebotomies and hydroxyurea. We emphasize that early diagnosis and effective treatment in such fulminant cases can be life saving. PMID- 27264626 TI - A Case of Catheter Related Septicemia Caused by Corynebacterium jeikeium. AB - Corynebacterium spp. has been gaining importance in immunosuppressive patients. This report of a 15-year-old girl with acute myeloblastic leukemia who developed catheter related septicemia with Corynebacterium jeikeium is presented to point out the importance of microorganisms of the normal flora, which were dismissed as contaminants in Clinical Microbiology Laboratories in the past. PMID- 27264627 TI - To the Memory of Prof. Dr. Muzaffer AKSOY. PMID- 27264628 TI - Characteristics of "Early Type-I Pattern" (0-6 years) Hodgkin's Disease in Turkish Children. AB - The clinico-epidemiologic characteristics of 54 children with HD in 0-6 years of age group were retrospectively analyzed. This group represented 27% of 200 HD cases observed in our center and was named as early type-I pattern HD. The association of EBV with HD was also shown by serologic and immunohistochemical methods (LMP1) in these very young Turkish patients. T-cell immune deficiency, cytokine imbalance and Zn deficiency were additional findings found in these patients. This series seems to be the largest one studying early type-I HD, by several aspects. PMID- 27264629 TI - Abnormal Hemoglobins in Turkey. AB - The presence of HbS was reported in Turkey for the first time in the late fifties by Aksoy et al. This was followed by other reports by the same author revealing the presence of several other abnormal hemoglobins in Turkey. So far up to present 42 abnormal hemoglobins have been identified in the Turkish population. In addition to the studies conducted in Turkey, many European researchers reported their findings in the immigrant Turkish population in their countries. This review tries to cover the tremendous efforts in this field. PMID- 27264630 TI - Images in Haematology. PMID- 27264631 TI - Melatonin mediates selenium-induced tolerance to cadmium stress in tomato plants. AB - Both selenium (Se) and melatonin reduce cadmium (Cd) uptake and mitigate Cd toxicity in plants. However, the relationship between Se and melatonin in Cd detoxification remains unclear. In this study, we investigated the influence of three forms of Se (selenocysteine, sodium selenite, and sodium selenate) on the biosynthesis of melatonin and the tolerance against Cd in tomato plants. Pretreatment with different forms of Se significantly induced the biosynthesis of melatonin and its precursors (tryptophan, tryptamine, and serotonin); selenocysteine had the most marked effect on melatonin biosynthesis. Furthermore, Se and melatonin supplements significantly increased plant Cd tolerance as evidenced by decreased growth inhibition, photoinhibition, and electrolyte leakage (EL). Se-induced Cd tolerance was compromised in melatonin-deficient plants following tryptophan decarboxylase (TDC) gene silencing. Se treatment increased the levels of glutathione (GSH) and phytochelatins (PCs), as well as the expression of GSH and PC biosynthetic genes in nonsilenced plants, but the effects of Se were compromised in TDC-silenced plants under Cd stress. In addition, Se and melatonin supplements reduced Cd content in leaves of nonsilenced plants, but Se-induced reduction in Cd content was compromised in leaves of TDC-silenced plants. Taken together, our results indicate that melatonin is involved in Se-induced Cd tolerance via the regulation of Cd detoxification. PMID- 27264632 TI - Late Effects after Umbilical Cord Blood Transplantation in Very Young Children after Busulfan-Based, Myeloablative Conditioning. AB - Infants and young children who undergo allogeneic cord blood transplantation (CBT) are at increased risk for late effects because of exposure of developing organs to chemotherapy and radiation therapy typically used in transplant conditioning regimens. Busulfan (Bu)-based myeloablative regimens were developed to eliminate radiation exposure in these young children with the hope that late effects would be minimized. We now describe the late effects in 102 consecutive patients surviving a minimum of 5 years (median follow-up, 12.9 years) post-CBT. Patients were conditioned with high-dose chemotherapy using Bu-containing regimens. No patient received total body irradiation. The median age at transplant was 1 year (range, .1 to 2). Diagnoses included inherited metabolic diseases (59.8%), leukemia (17.6%), congenital immune deficiency (20.2%), bone marrow failure/myelodysplastic syndrome (3.9%), and hemoglobinopathy (2%). Among patients surviving 5 years, the overall survival rate at 10 years post-CBT was 93% (95% CI, 84.9 to 96.8). Virtually all patients (98%) experienced at least 1 significant late effect. Most (83.3%) experienced 2 or more late effects, and more than half of the patients (64.7%) experienced 3 or more late effects. The most commonly observed late effects included dental problems (92.2%), short stature (55.9%), cognitive deficits (53.6%), pulmonary dysfunction (18.6%), and abnormal pubertal development (27.9%). This is the first report of late effects of Bu-based conditioning in a cohort of very young patients at the time of transplant. These results will inform clinical care guidelines for long-term follow-up and add to the growing information regarding outcomes of hematopoietic stem cell transplantation. PMID- 27264634 TI - Allografts for Follicular Non-Hodgkin Lymphoma: Why Never Is No Longer an Acceptable Answer. PMID- 27264633 TI - Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research. AB - The European Society for Blood and Marrow Transplant Research data set was used to retrospectively analyze the outcomes of hypomethylating therapy (HMA) compared with those of conventional chemotherapy (CC) before hematopoietic stem cell transplantation (HSCT) in 209 patients with advanced myelodysplastic syndromes. Median follow-up was 22.1 months and the median age of the group was 57.6 years with 37% of the population older than > 60 years. The majority of patients (59%) received reduced-intensity conditioning and 34% and 27% had intermediate-2 and high international prognostic scoring system (IPSS) scores. At time of HSCT, 32% of patients did not achieve complete remission (CR) and 13% had primary refractory disease. On univariate analysis, outcomes at 3 years were not significantly different between HMA and CC for overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM): OS (42% versus 35%), RFS (29% versus 31%), CIR (45% versus 40%), and NRM (26% versus 28%). Comparing characteristics of the groups, there were more patients < 55 years old, more patients in CR (68% versus 32%), and fewer patients with primary refractory disease in the CC group than in the HMA group (10% versus 19%, P < .001). Patients with primary refractory disease had worse outcomes than those in CR with regard to OS (hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.41 to 4.13; P = .001), RFS (HR, 2.27; 95% CI, 1.37 to 3.76; P = .001), and NRM (HR, 2.49; 95% CI, 1.18 to 5.26; P = .016). In addition, an adverse effect of IPSS-R cytogenetic risk group was evident for RFS. In summary, outcomes after HSCT are similar for patients receiving HMA compared with those receiving CC, despite the higher proportion of patients with primary refractory disease in the HMA group. PMID- 27264635 TI - The interconnected rhizosphere: High network complexity dominates rhizosphere assemblages. AB - While interactions between roots and microorganisms have been intensively studied, we know little about interactions among root-associated microbes. We used random matrix theory-based network analysis of 16S rRNA genes to identify bacterial networks associated with wild oat (Avena fatua) over two seasons in greenhouse microcosms. Rhizosphere networks were substantially more complex than those in surrounding soils, indicating the rhizosphere has a greater potential for interactions and niche-sharing. Network complexity increased as plants grew, even as diversity decreased, highlighting that community organisation is not captured by univariate diversity. Covariations were predominantly positive (> 80%), suggesting that extensive mutualistic interactions may occur among rhizosphere bacteria; we identified quorum-based signalling as one potential strategy. Putative keystone taxa often had low relative abundances, suggesting low-abundance taxa may significantly contribute to rhizosphere function. Network complexity, a previously undescribed property of the rhizosphere microbiome, appears to be a defining characteristic of this habitat. PMID- 27264637 TI - A canonical correlation analysis based method for contamination event detection in water sources. AB - In this study, a general framework integrating a data-driven estimation model is employed for contamination event detection in water sources. Sequential canonical correlation coefficients are updated in the model using multivariate water quality time series. The proposed method utilizes canonical correlation analysis for studying the interplay between two sets of water quality parameters. The model is assessed by precision, recall and F-measure. The proposed method is tested using data from a laboratory contaminant injection experiment. The proposed method could detect a contamination event 1 minute after the introduction of 1.600 mg l(-1) acrylamide solution. With optimized parameter values, the proposed method can correctly detect 97.50% of all contamination events with no false alarms. The robustness of the proposed method can be explained using the Bauer-Fike theorem. PMID- 27264636 TI - Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes. AB - Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity. PMID- 27264639 TI - Effects of full-fat rice bran inclusion in diets on growth performance and meat quality of Sichuan goose. AB - This trial was conducted to study the effect of full-fat rice bran inclusion in diets on growth performance, carcass and meat quality and fatty acid composition in Sichuan goose. A total of 204 Sichuan white male geese (28-d-old, 984 +/- 15 g) were used in the 42-d assay. Full-fat rice bran inclusion in diets was 0%, 6%, 12% and 18%, respectively. On d 70, two geese from each pen were randomly selected and killed for measuring the carcass and meat quality and the meat fatty acid composition. The results showed that full-fat rice bran inclusion had no effect on average daily gain during 28-56 d, but rice bran inclusion at 18% increased average daily gain during 57-70 d. In addition, the full-fat rice bran supplementation decreased the subcutaneous fat yield, and the inclusion of full fat rice bran in amounts of 12% and 18% decreased the half-eviscerated carcass yield, eviscerated carcass yield and crude fat content in goose meat. Moreover, full-fat rice bran supplementation had no effect on the content of total saturated fatty acid (SFA), but decreased the content of total monounsaturated fatty acid (MUFA). The inclusion of full-fat rice bran in amounts of 12-18% increased the content of total polyunsaturated fatty acid (PUFA) and total n-6 in goose meat and in the amount of 18% increased n-3 fatty acids content in goose meat. The results indicated that the rice bran inclusion had a positive effect in geese by stimulating growth performance and improving meat quality and fatty acid composition of goose meat. PMID- 27264638 TI - Reversibility of endothelial dysfunction in diabetes: role of polyphenols. AB - The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis. PMID- 27264640 TI - Composition of cuticular waxes coating flag leaf blades and peduncles of Triticum aestivum cv. Bethlehem. AB - The work herein presents comprehensive analyses of the cuticular wax mixtures covering the flag leaf blade and peduncle of bread wheat (Triticum aestivum) cv. Bethlehem. Overall, Gas Chromatography-Mass Spectrometry and Flame Ionization Detection revealed a wax coverage of flag leaf blades (16 MUg/cm(2)) a third that of peduncles (49 MUg/cm(2)). Flag leaf blade wax was dominated by 1-alkanols, while peduncle wax contained primarily beta-diketone and hydroxy-beta-diketones, thus suggesting differential regulation of the acyl reduction and beta-diketone biosynthetic pathways in the two analyzed organs. The characteristic chain length distributions of the various wax compound classes are discussed in light of their individual biosynthetic pathways and biosynthetic relationships between classes. Along with previously reported wheat wax compound classes (fatty acids, 1 alkanols, 1-alkanol esters, aldehydes, alkanes, beta-diketone, hydroxy-beta diketones, alkylresorcinols and methyl alkylresorcinols), esters of 2-alkanols and three types of aromatic esters (benzyl, phenethyl and p-hydroxyphenethyl) are also reported. In particular, 2-heptanol esters were identified. Detailed analyses of the isomer distributions within 1-alkanol and 2-alkanol ester homologs revealed distinct patterns of esterified acids and alcohols, suggesting several wax ester synthases with very different substrate preferences in both wheat organs. Terpenoids, including two terpenoid esters, were present only in peduncle wax. PMID- 27264641 TI - Carlactone-type strigolactones and their synthetic analogues as inducers of hyphal branching in arbuscular mycorrhizal fungi. AB - Hyphal branching in the vicinity of host roots is a host recognition response of arbuscular mycorrhizal fungi. This morphological event is elicited by strigolactones. Strigolactones are carotenoid-derived terpenoids that are synthesized from carlactone and its oxidized derivatives. To test the possibility that carlactone and its oxidized derivatives might act as host-derived precolonization signals in arbuscular mycorrhizal symbiosis, carlactone, carlactonoic acid, and methyl carlactonoate as well as monohydroxycarlactones, 4 , 18-, and 19-hydroxycarlactones, were synthesized chemically and evaluated for hyphal branching-inducing activity in germinating spores of the arbuscular mycorrhizal fungus Gigaspora margarita. Hyphal branching activity was found to correlate with the degree of oxidation at C-19 methyl. Carlactone was only weakly active (100 ng/disc), whereas carlactonoic acid showed comparable activity to the natural canonical strigolactones such as strigol and sorgomol (100 pg/disc). Hydroxylation at either C-4 or C-18 did not significantly affect the activity. A series of carlactone analogues, named AD ester and AA'D diester, was synthesized by reacting formyl Meldrum's acid with benzyl, cyclohexylmethyl, and cyclogeranyl alcohols (the A-ring part), followed by coupling of the potassium enolates of the resulting formylacetic esters with the D-ring butenolide. AD ester analogues exhibited moderate activity (1 ng-100 pg/disc), while AA'D diester analogues having cyclohexylmethyl and cyclogeranyl groups were highly active on the AM fungus (10 pg/disc). These results indicate that the oxidation of methyl to carboxyl at C-19 in carlactone is a prerequisite but BC-ring formation is not essential to show hyphal branching activity comparable to that of canonical strigolactones. PMID- 27264642 TI - Comparative analysis of carbohydrate residues in the midgut of phlebotomines (Diptera: Psychodidae) from colony and field populations from Amazon, Brazil. AB - Leishmaniasis are worldwide diseases that occur in 98 countries including Brazil, transmitted by the bite of female phlebotomines during blood feeding. In Brazil it is known that some species of sand flies as Lutzomyia longipalpis sensun latum (vector of Leishmania infantum chagasi), Lutzomyia flaviscutellata (vector of Leishmania (Leishmania) amazonensis) and Lutzomyia antunesi [suspected vector of Leishmania (Viannia) lindenbergi] are incriminated of transmitting the parasite Leishmania for the vertebrate host. The phlebotomine-parasite is mediated by the attachment of the promastigote lipophosphoglycan (LPG) to the midgut epithelium. However, another mechanism that is LPG-independent and mediated by N-acetyl galactosamine (GalNAc) seems to occur in some species of phlebotomines that are classified as permissive. The aim of this study was to characterize the carbohydrate residues that, probably, play a role in parasite attachment to the midgut of phlebotomine from colony and field populations from the Brazilian Amazonian region. We observed the presence of GalNAc, mannose, galactose and GlcNAc in all phlebotomine species. A binding assay between L. (L.) amazonensis and L. i.chagasi to the midguts of different species of phlebotomines was performed. The attachment of both Leishmania and vector species suggests the presence of GalNAc on the midgut surfaces. Thus, these results suggested that GalNAc is a possible binding sites of Leishmania in sand flies from the Brazilian Amazonian region. PMID- 27264643 TI - Social apoptosis in honey bee superorganisms. AB - Eusocial insect colonies form superorganisms, in which nestmates cooperate and use social immunity to combat parasites. However, social immunity may fail in case of emerging diseases. This is the case for the ectoparasitic mite Varroa destructor, which switched hosts from the Eastern honeybee, Apis cerana, to the Western honey bee, Apis mellifera, and currently is the greatest threat to A. mellifera apiculture globally. Here, we show that immature workers of the mite's original host, A. cerana, are more susceptible to V. destructor infestations than those of its new host, thereby enabling more efficient social immunity and contributing to colony survival. This counterintuitive result shows that susceptible individuals can foster superorganism survival, offering empirical support to theoretical arguments about the adaptive value of worker suicide in social insects. Altruistic suicide of immature bees constitutes a social analogue of apoptosis, as it prevents the spread of infections by sacrificing parts of the whole organism, and unveils a novel form of transgenerational social immunity in honey bees. Taking into account the key role of susceptible immature bees in social immunity will improve breeding efforts to mitigate the unsustainably high colony losses of Western honey bees due to V. destructor infestations worldwide. PMID- 27264644 TI - Analysis of deoxynivalenol and deoxynivalenol-3-glucosides content in Canadian spring wheat cultivars inoculated with Fusarium graminearum. AB - Contamination of wheat grains with Fusarium mycotoxins and their modified forms is an important issue in wheat industry. The objective of this study was to analyse the deoxynivalenol (DON) and deoxynivalenol-3-glucosides (D3G) content in Canadian spring wheat cultivars grown in two locations, inoculated with a mixture of 3-acetyldeoxynivalenol (3-ADON)-producing Fusarium graminearum strains and a mixture of 15-acetlyldeoxynivalenol (15-ADON)-producing F. graminearum strains. According to the analysis of variance, significant differences were observed among the cultivars for Fusarium head blight (FHB) disease index, Fusarium damaged kernel percentage (%FDK), DON content and D3G content. When the effect of chemotype was considered, significant differences were observed for FHB disease index, FDK percentage and DON content. The D3G content and D3G/DON ratio were not significantly different between the chemotypes, except for D3G content at the Winnipeg location. The Pearson correlation coefficient between DON and D3G was 0.84 and 0.77 at Winnipeg and Carman respectively. The highest D3G/DON ratio was observed in cultivars Carberry (44%) in Carman and CDC Kernen (63.8%) in Winnipeg. The susceptible cultivars showed lower D3G/DON ratio compared with the cultivars rated as moderately resistant and intermediate. The current study indicated that Canadian spring cultivars produce D3G upon Fusarium infection. PMID- 27264645 TI - Reciprocal Effects of Self-Regulation, Semantic Knowledge, and Reading Comprehension in Early Elementary School. AB - Many assume that cognitive and linguistic processes, such as semantic knowledge (SK) and self-regulation (SR), subserve learned skills like reading. However, complex models of interacting and bootstrapping effects of SK, SR, instruction, and reading hypothesize reciprocal effects. Testing this "lattice" model with children (n = 852) followed from first to second grade (5.9-10.4 years of age) revealed reciprocal effects for reading and SR, and reading and SK, but not SR and SK. More effective literacy instruction reduced reading stability over time. Findings elucidate the synergistic and reciprocal effects of learning to read on other important linguistic, self-regulatory, and cognitive processes; the value of using complex models of development to inform intervention design; and how learned skills may influence development during middle childhood. PMID- 27264646 TI - Immobilization of horseradish peroxidase on amidoximated acrylic polymer activated by cyanuric chloride. AB - Horseradish peroxidase (HRP) was immobilized on amidoximated acrylic fabric after being activated with cyanuric chloride. FT-IR spectroscopy and scanning electron microscopy were used to characterize fabrics. The maximum immobilization efficiency of HRP (70%) was detected at 4% cyanuric chloride and pH 7.0. The immobilized enzyme retained 45% of its initial activity after ten reuses. The immobilization of enzyme on the carrier is saturated after 6h of incubation time. The pH was shifted from 7.0 for soluble HRP to 7.5-8.0 for the immobilized enzyme. The soluble HRP and immobilized HRP had the same optimum activity at 40 degrees C. The immobilized HRP is more thermal stable than soluble HRP. Substrate analogues were oxidized by immobilized HRP with higher efficiencies than those of soluble HRP. Km values of the soluble HRP and the immobilized HRP were 31 and 37mM for guiacol and 5.0 and 7.8mM for H2O2, respectively. The immobilized HRP had higher efficiency for removal of phenol than that of soluble HRP. The immobilized HRP had higher resistance toward heavy metal ions compared to the soluble enzyme. The immobilized HRP was more stable against high concentration of urea, Triton X-100 and isopropanol. The immobilized HRP exhibited high resistance to proteolysis by trypsin than soluble enzyme. In conclusion, the immobilized HRP could be used as a potential efficient catalyst for the removal of aromatic pollutants from wastewater. PMID- 27264647 TI - Localization and in silico study of the vegetative insecticidal proteins Vip2S Vip1S of Bacillus thuringiensis. AB - The Bacillus thuringiensis S1/4 strain was previously found to harbour vip1S, vip2S, and vip3 genes. Its plasmid curing led to the obtaining of four partially cured strains S1/4-2, S1/4-3, S1/4-7, and S1/4-9 (vip2S-vip1S (-), vip3 (+)), one strain S1/4-4 (vip2S-vip1S (+), vip3 (-)), and S1/4-0 strain lacking the three genes. Using these derivative strains as templates, PCR amplification and southern blot assay revealed that vip2S-vip1S operon and vip3 gene were localized on two different large plasmids. Bioinformatics studies showed that vip2S (1.356 kb), and vip1S (2.637 kb) genes are encoding by an operon consisting of two ORFs separated by an intergenic spacer of 4bp. Using the InterPro tool, Vip2S was found to belong to the family of Binary exotoxin A and Vip1S to bacterial exotoxin B. In silico modeling indicated that the 3D structure of Vip2S is a mixed alpha/beta protein and proposed 3D-model of Vip1S. Bioassays of the partially cured strains supernatants showed a weak toxicity of S1/4-4 to the lepidopteran Spodoptera littoralis comparing to a better effect of S1/4-2, S1/4 3, S1/4-7, and S1/4-9, suggesting its eventual contribution to the toxicity. Nevertheless, the concentrated supernatant of S1/4-4 strain was not toxic against the coleopteran Tribolium castaneum. PMID- 27264648 TI - Rutin-encapsulated chitosan nanoparticles targeted to the brain in the treatment of Cerebral Ischemia. AB - OBJECTIVE: Rutin, a potent antioxidant, has been reported to reduce the risk of ischemic disease. Our study aims to prepare rutin-encapsulated-chitosan nanoparticles (RUT-CS-NPs) via ionic gelation method and determine its results, based on different parameters i.e. surface morphology characterization, in-vitro or ex-vivo release, dynamic light scattering and differential scanning calorimetry (DSC), for treating cerebral ischemia. METHODS: UPLC-ESI-Q-TOF-MS/MS was used to evaluate the optimized RT-CS-NPs1 for brain-drug uptake as well as to follow-up the pharmacokinetics, bio-distrbution, brain-targeting efficiency and potential after intranasal administration (i.n.). KEY FINDINGS: A particle size of <100nm for the formulation, significantly affected by drug:CS ratio, and entrapment efficiency and loading capacity of 84.98%+/-4.18% and 39.48%+/-3.16%, respectively were observed for RUT. Pharmacokinetics, bio-distribution, brain targeting efficiency (1443.48+/-39.39%) and brain drug-targeting potential (93.00+/-5.69%) showed enhanced bioavailability for RUT in brain as compared to intravenous administration. In addition; improved neurobehavioral activity, histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO) induced cerebral ischemic rats model after i.n. administration of RUT-CS-NPs. CONCLUSION: A significant role of mucoadhesive-RT CS-NPs1 as observed after high targeting potential and efficiency of the formulation prove; RUT-CS-NPs are more effectively accessed and target easily the brain. PMID- 27264649 TI - Preclinical assessment of scleral lens as a reservoir-based ocular therapeutic system. AB - PURPOSE: Bacterial keratitis is a sight threatening infection of the cornea which remains one of the most important potential complications of contact lens use. If the corneal ulcer is small, peripheral with no impending perforation present, intensive monotherapy with fluoroquinolones could be used. Therefore, a study was conducted with the objective to provide pharmacological data of the intra-ocular diffusion after administration of Ofloxacin using a scleral lens reservoir, as well as an evaluation of surface tolerability in rabbits. MATERIALS AND METHODS: Samples of corneas, aqueous humor and vitreous were collected to measure the drug levels of Ofloxacin using High Performance Liquid Chromatography. The corneas were examined by electron microscopy scanning and the eyeballs by light polarizing microscopy in order to evaluate surface tolerability. RESULTS: Ofloxacin levels found in the aqueous humor and cornea were higher than those previously reported. The mean Ofloxacin corneal levels exceeded the MIC (Minimum Inhibitory Concentration) for which 90% of isolates are indicated for all bacteria implicated in keratitis. CONCLUSION: To our knowledge, this is the first preclinical study assessing local tolerance and intra-ocular diffusion of Ofloxacin after administration using a scleral lens reservoir. PMID- 27264661 TI - Dear members of Turkish Society of Haematology. PMID- 27264662 TI - Thrombocytosis in solid tumors: review of the literature. PMID- 27264663 TI - Failure of puberty and linear growth in beta-thalassemia major. AB - Thalassemia major is a severe progressive hemolytic anemia and a serious medical problem worldwide. Endocrine dysfunctions are well described in patients with thalassemia major. Data for endocrine complications from developing countries are scant. Endocrine complications in developing countries may be frequent due to suboptimal iron chelation. The aim of this study was to evaluate the prevalence of delayed puberty and growth failure in patients with beta-thalassemia major. We evaluated the growth and sexual development of 146 patients with thalassemia major aged 10-22 years. The following data were recorded in questionnaire, age, sex, height, weight, serum ferritin levels and pubertal staging. Failure of puberty was present in 75.6% of boys and 68.4% of girls aged 12-22 years. Gonadotropin insufficiency was found in most of the patients with lack of puberty. There was a significant difference between the height of patients with pubertal development (153 +/- 9.1 cm) and those with delayed puberty (140 +/- 9.1), (p< 0.001). Short stature was present in 65.7% of patients. Sixty-nine percent of boys and 62.9% of girls were found to be less than 2 SD below the mean for normal height; after the age of 12, the percentage was 78.9% in girls and 83.8% in boys after the age of 14. We conclude that failure of puberty and impaired growth are very common in our thalassemic patients which necessitates newer protocols of treatment, correct blood transfusion and chelation therapy. PMID- 27264660 TI - Induction of Germ Cell-like Cells from Porcine Induced Pluripotent Stem Cells. AB - The ability to generate germ cells from pluripotent stem cells (PSCs) is valuable for human regenerative medicine and animal breeding. Germ cell-like cells (GCLCs) have been differentiated from mouse and human PSCs, but not from porcine PSCs, which are considered an ideal model for stem cell applications. Here, we developed a defined culture system for the induction of primordial germ cell-like cells (PGCLCs) from porcine induced PSCs (piPSCs). The identity of the PGCLCs was characterized by observing cell morphology, detecting germ cell marker gene expression and evaluating epigenetic properties. PGCLCs could further differentiate into spermatogonial stem cell-like cells (SSCLCs) in vitro. Importantly, meiosis occurred during SSCLC induction. Xenotransplantation of GCLCs into seminiferous tubules of infertile immunodeficient mice resulted in immunohistochemically identifiable germ cells in vivo. Overall, our study provides a feasible strategy for directing piPSCs to the germ cell fate and lays a foundation for exploring germ cell development mechanisms. PMID- 27264664 TI - Evaluation of inherited and acquired platelet function disorders in iron deficient women with menorrhagia by whole blood lumi-aggregometer. AB - The commonest cause of iron deficiency anemia (IDA) in premenopausal women is often menstrual blood loss. However, no organic pathology is identified in more than 50% of menorrhagic women. We therefore investigated inherited and acquired bleeding disorders among women with unexplained menorrhagia who developed IDA. In vitro whole blood platelet aggregation (PA) with ADP, arachidonic acid (AA), ristocetin and collagen was studied in addition to full blood count, serum iron levels, serum iron binding capacity, transferrin saturation, ferritin, prothrombin and activated partial thromboplastin time, fibrinogen, D-Dimer, Factor VIII, Factor IX, Factor XI, ristocetin cofactor activity, blood type and bleeding time in 67 women before and after therapy. Before therapy; decreased agonist induced PA was observed in 20% of women by ADP, in 12% by AA, in 2% by ristocetin and in 6% by collagen. After oral iron therapy, decreased platelet aggregation was shown in 8% of women with ADP and 2% of women with AA while initial abnormal ristocetin and collagen induced platelet aggregation responses became normal. Also there was a statistically significant increase of ristocetin cofactor activities and FXI levels after iron repletion. We conclude that; rather than von Willebrand disease, platelet function abnormalities and FXI deficiency are the most common hemostatic disorders in women with unexplained menorrhagia and significant portion of these disorders can be reversed by iron therapy. PMID- 27264665 TI - Allogeneic stem cell transplantation in chronic myeloid leukemia two and a half year experience. AB - This study is performed to evaluate outcome of allogeneic stem cell transplantation (SCT) in chronic myeloid leukemia at Armed Forces Bone Marrow Transplant Centre, Rawalpindi from Apr 2002 to Oct 2004. Twenty-two patients with CML underwent allogeneic SCT from HLA matched siblings. Patients were divided into standard (n= 14) and high-risk (n= 8) groups. Patients were subjected to conditioning regimens consisting of busulphan and cyclophosphamide. Cyclosporin, prednisolone and methotrexate were given for GVHD prophylaxis. All donors were subjected to PBSC harvest after G-CSF therapy for five days. All patients received G-CSF from day + 5 until ANC > 0.5 x 109/L. The median age of the patients was 29 years (range 7-53 years) with a male to female ratio of 6.3: 1. Engraftment was achieved in all patients. Median time to achieve neutrophil (ANC 0.5 x 109/L) and platelet (20 x 109/L) recovery was 13 days and 12 days respectively. Median stay in hospital was 18 days. Acute GVHD (Grade II-IV) was observed in eleven patients (50%) while chronic GVHD was seen in four patients (18%). One patient relapsed 8 months post-transplant. Two patients (9%) developed VOD liver. One patient had haemorrhagic cystitis. Four patients (18%) developed post-transplant infectious complications, which included Pseudomonas septicemia, aspergillosis, tuberculous pleural effusion and herpes zoster. Overall mortality was 22.7% (n= 5). The major causes of mortality were VOD liver, GVHD grade IV, Pseudomonas septicemia and aspergillosis. Overall survival was 77.2% (n= 17) and disease free survival was (n= 16) 72.7%. Follow up ranges from 23 to 828 days (median 212 days). The preliminary results of SCT in this small series of patients with CML are very encouraging. To improve the long-term survival it is imperative that patients are transplanted early after diagnosis and conditioning regimens are selected carefully. PMID- 27264666 TI - The effect of a nationwide antibiotic restriction policy on antibiotic usage in a stem cell transplantation unit. AB - The Turkish Ministry of Health has released a regulation in February 2003 in order to decrease, first the antibiotic expenses and second, inappropriate use of antimicrobial agents. The aim of this study is to assess the impact of this nationwide antibiotic restriction (NAR) in the most active stem cell transplantation unit (SCTU) in Turkey. All patients followed up in SCTU and had received antimicrobial therapy in the period of four months before and after NAR were evaluated retrospectively. The appropriateness of antimicrobial treatments was assessed by two ID specialists and one ID professor. Disagreements between investigators were solved by discussion and review of published guidelines. There were 10 and 25 patients who were on antimicrobial therapy in the 1st (before NAR) and 2nd (after NAR) group, respectively. Seventeen of the patients had undergone allogeneic stem cell transplantation, while 6 were allogeneic bone marrow recipients and 12 were autologous peripheral stem cell recipients. The antibiotic days per patient was 33.4 and 19.4 in the first and second groups respectively (p=0.036). Although it was not significant, the appropriateness of antibiotic regimens used in the second group was higher than the first group (OR: 5, CI: 0.9 26.4, p= 0.059). The significantly lower antibiotic day per patient in the 2nd group may be the result of collaboration between infectious diseases and hematology physicians settled after NAR in our hospital. NAR had reduced the antimicrobial use in our unit mainly by providing collaboration between infectious diseases and hematology departments. PMID- 27264667 TI - A rare syndrome that can easily be missed: May-Hegglin anomaly. AB - May-Hegglin is a rare disease characterized by macrothrombocytopenia and presence of Dohle-like bodies in white cells. We present a patient treated with acute myeloid leukemia had pale-blue colored inclusion bodies assuming Dohle in his neutrophils. PMID- 27264668 TI - Development of autoimmune hemolytic anemia during the treatment of a patient with acute myelomonocytic leukemia. AB - Drug induced autoimmune hemolytic anemia is a well-known complication of drug therapy but it is often misdiagnosed. Drug induced autoimmune hemolytic anemia is difficult to differantiate from classical autoimmune hemolytic anemia. Here, we have reported a case with autoimmune hemolytic anemia might be caused by drugs such as teicoplanin, imipenem and amphotericin B. In our case, on the fifteenth postadmission day was occur autoimmune hemolytic anemia. At this while, chemotherapy of patient had been completed and the patient have been taking antibiotherapy which include teicoplanin, imipenem and amphotericin B. Antibiotherapy could not be stopped because of febrile neutropenia. Symptoms and sings of anemia improved with prednisolon therapy. Suspicious drug must be stopped in drug induced autoimmune hemolytic anemia but in the conditions that drug could not be stopped, steroid treatment can be used in the treatment of hemolytic anemia. PMID- 27264669 TI - Images in Hematology. PMID- 27264670 TI - Azadipyrromethene cyclometalation in neutral Ru(II) complexes: photosensitizers with extended near-infrared absorption for solar energy conversion applications. AB - In the on-going quest to harvest near-infrared (NIR) photons for energy conversion applications, a novel family of neutral ruthenium(ii) sensitizers has been developed by cyclometalation of an azadipyrromethene chromophore. These rare examples of neutral ruthenium complexes based on polypyridine ligands exhibit an impressive panchromaticity achieved by the cyclometalation strategy, with strong light absorption in the 600-800 nm range that tails beyond 1100 nm in the terpyridine-based adducts. Evaluation of the potential for Dye-Sensitized Solar Cells (DSSC) and Organic Photovoltaic (OPV) applications is made through rationalization of the structure-property relationship by spectroscopic, electrochemical, X-ray structural and computational modelization investigations. Spectroscopic evidence for photo-induced charge injection into the conduction band of TiO2 is also provided. PMID- 27264672 TI - Re-imagining dementia in the fourth age: the ironic fictions of Alice Munro. AB - This paper analyses two stories by Alice Munro to explore how her fiction interrogates the prevailing social imaginary of the fourth age. Drawing on the theory of Gilleard and Higgs, I show how Munro's stories rely on irony and surreal imagery to subvert the logic that engenders and normalises the opposition between the third and fourth ages, and, by extension, the social death of people coping with later-life dementia. Ultimately, I argue that Munro's fiction does not so much reveal the Truth about the fourth age, as expose the reader's complicity in the construction of the prevailing gothic social imaginary. PMID- 27264671 TI - Dynamic Contrast Enhanced MRI Assessing the Antiangiogenic Effect of Silencing HIF-1alpha with Targeted Multifunctional ECO/siRNA Nanoparticles. AB - Stabilization of hypoxia inducible factor 1alpha (HIF-1alpha), a biomarker of hypoxia, in hypoxic tumors mediates a variety of downstream genes promoting tumor angiogenesis and cancer cell survival as well as invasion, and compromising therapeutic outcome. In this study, dynamic contrast enhanced MRI (DCE-MRI) with a biodegradable macromolecular MRI contrast agent was used to noninvasively assess the antiangiogenic effect of RGD-targeted multifunctional lipid ECO/siHIF 1alpha nanoparticles in a mouse HT29 colon cancer model. The RGD-targeted ECO/siHIF-1alpha nanoparticles resulted in over 50% reduction in tumor size after intravenous injection at a dose of 2.0 mg of siRNA/kg every 3 days for 3 weeks compared to a saline control. DCE-MRI revealed significant decline in vascularity and over a 70% reduction in the tumor blood flow, permeability-surface area product, and plasma volume fraction vascular parameters in the tumor treated with the targeted ECO/siHIF-1alpha nanoparticles. The treatment with targeted ECO/siRNA nanoparticles resulted in significant silencing of HIF-1alpha expression at the protein level, which also significantly suppressed the expression of VEGF, Glut-1, HKII, PDK-1, LDHA, and CAIX, which are all important players in tumor angiogenesis, glycolytic metabolism, and pH regulation. By possessing the ability to elicit a multifaceted effect on tumor biology, silencing HIF-1alpha with RGD-targeted ECO/siHIF-1alpha nanoparticles has great promise as a single therapy or in combination with traditional chemotherapy or radiation strategies to improve cancer treatment. PMID- 27264673 TI - A novel rasopathy caused by recurrent de novo missense mutations in PPP1CB closely resembles Noonan syndrome with loose anagen hair. AB - Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS LAH) is characterized by its distinctive hair anomalies, developmental differences, and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. SHOC2 forms a complex with protein phosphatase 1 (PP1C). Protein phosphatases counterbalance kinases and control activation of signaling proteins, such as the mitogen-activated protein kinases of the RAS/MAPK pathway. Here we report four patients with de novo missense mutations in protein phosphatase one catalytic subunit beta (PPP1CB), sharing a recognizable phenotype. Three individuals had the recurrent PPP1CB c.146G>C, p.Pro49Arg mutation, the fourth had a c.166G>C, p.Ala56Pro change. All had relative or absolute macrocephaly, low-set and posteriorly angulated ears, and developmental delay. Slow growing and/or sparse hair and/or an unruly hair texture was present in all. Three individuals had feeding difficulties requiring feeding tubes. One of two males had cryptorchidism, another had pectus excavatum. Short stature was present in three. A female with the recurrent mutation had a Dandy-Walker malformation and optic nerve hypoplasia. Mild ventriculomegaly occurred in all, cerebellar tonsillar ectopia was seen in two and progressed to Chiari 1 malformation in one individual. Based on the combination of phenotypic findings and PPP1CB's effect on RAF dephosphorylation within the RAS/MAPK pathway, this novel condition can be considered a rasopathy, most similar to NS-LAH. Collectively, these mutations meet the standardized criteria for pathogenicity. (c) 2016 Wiley Periodicals, Inc. PMID- 27264674 TI - Genetic alterations of differentiated thyroid carcinoma in iodine-rich and iodine deficient countries. AB - BRAF V600E mutation, RET rearrangements, and RAS mutations are the common genetic alterations in differentiated thyroid carcinomas derived from follicular thyroid cells. However, the relationship between these alterations and iodine intake is still controversial. To clarify the influence of iodine intake on the occurrence of differentiated thyroid carcinomas, we performed molecular analyses for two differentiated carcinomas, papillary thyroid carcinomas (PTCs) and follicular thyroid carcinomas (FTCs), from an iodine-rich country (Japan) and an iodine deficient country (Vietnam). We examined 120 PTCs (67 Japanese and 53 Vietnamese) and 74 FTCs (51 Japanese and 23 Vietnamese). We carried out allele-specific polymerase chain reaction (AS-PCR) for BRAF V600E, PCR and direct sequencing for RAS mutations (codon 12, 13, and 61 in NRAS, HRAS, and KRAS), and RT-PCR for RET/PTC1 and RET/PTC3. BRAF V600E was present in 55/67 (82.1%) Japanese PTCs and 44/53 (83%) Vietnamese PTCs. RET/PTC1 was identified in only one PTC from each country, and no samples had RET/PTC3. NRAS mutation was found in 17/51 (33.3%) Japanese FTCs and 4/23 (17.4%) Vietnamese FTCs. NRAS mutation was cited in codon 61 (20 cases) and codon 12 (one case). None of FTCs had KRAS or HRAS mutations. There were no significant differences in the prevalence of BRAF V600E, RET/PTC, or RAS mutations between the two countries. Our study showed no differences in genetic alterations of thyroid cancers from iodine-rich and iodine-deficient countries, possibly suggesting that iodine intake might not affect the genetic alterations of differentiated thyroid cancer. PMID- 27264675 TI - Labelling of endogenous target protein via N-S acyl transfer-mediated activation of N-sulfanylethylanilide. AB - The ligand-dependent incorporation of a reporter molecule (e.g., fluorescence dye or biotin) onto a endogenous target protein has emerged as an important strategy for elucidating protein function using various affinity-based labelling reagents consisting of reporter, ligand and reactive units. Conventional labelling reagents generally use a weakly activated reactive unit, which can result in the non-specific labelling of proteins in a ligand-independent manner. In this context, the activation of a labelling reagent through a targeted protein-ligand interaction could potentially overcome the problems associated with conventional affinity-based labelling reagents. We hypothesized that this type of protein ligand-interaction-mediated activation could be accomplished using N sulfanylethylanilide (SEAlide) as the reactive unit in the labelling reagent. Electrophilically unreactive amide-type SEAlide can be activated by its conversion to the corresponding active thioester in the presence of a phosphate salt, which can act as an acid-base catalyst. It has been suggested that protein surfaces consisting of hydrophilic residues such as amino, carboxyl and imidazole groups could function as acid-base catalysts. We therefore envisioned that a SEAlide-based labelling reagent (SEAL) bearing SEAlide as a reactive unit could be activated through the binding of the SEAL with a target protein. Several SEALs were readily prepared in this study using standard 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase protocols. These SEAL systems were subsequently applied to the ligand-dependent labelling of human carbonic anhydrase (hCA) and cyclooxyganese 1. Although we have not yet obtained any direct evidence for the target protein-mediated activation of the SEAlide unit, our results for the reaction of these SEALs with hCA1 or butylamine indirectly support our hypothesis. The SEALs reported in this study represent valuable new entries to the field of affinity-based labelling reagents and are expected to show great utility in protein labelling. PMID- 27264676 TI - Solubility of alkali metal halides in the ionic liquid [C4C1im][OTf]. AB - The solubilities of the metal halides LiF, LiCl, LiBr, LiI, NaF, NaCl, NaBr, NaI, KF, KCl, KBr, KI, RbCl, CsCl, CsI, were measured at temperatures ranging from 298.15 to 378.15 K in the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate ([C4C1im][OTf]). Li(+), Na(+) and K(+) salts with anions matching the ionic liquid have also been investigated to determine how well these cations dissolve in [C4C1im][OTf]. This study compares the influence of metal cation and halide anion on the solubility of salts within this ionic liquid. The highest solubility found was for iodide salts, and the lowest solubility for the three fluoride salts. There is no outstanding difference in the solubility of salts with matching anions in comparison to halide salts. The experimental data were correlated employing several phase equilibria models, including ideal mixtures, van't Hoff, the lambdah (Buchowski) equation, the modified Apelblat equation, and the non-random two-liquid model (NRTL). It was found that the van't Hoff model gave the best correlation results. On the basis of the experimental data the thermodynamic dissolution parameters (DeltaH, DeltaS, and DeltaG) were determined for the studied systems together with computed gas phase metathesis parameters. Dissolution depends on the energy difference between enthalpies of fusion and dissolution of the solute salt. This demonstrates that overcoming the lattice energy of the solid matrix is the key to the solubility of inorganic salts in ionic liquids. PMID- 27264677 TI - Luminescence responsive intracluster rearrangements of gold(i)-silver(i) clusters triggered by acetonitrile. AB - A gold(i)-silver(i) cluster bearing six carboxylate groups has been synthesized through the oxidation of its aldehyde precursor and the Au6 core of this cluster displays an octahedral or a trigonal prismatic configuration depending on the crystallization conditions. The reversible interconversion between these two isomers can be triggered in the solid state by the addition or removal of acetonitrile solvent molecules. Interestingly, luminescence changes were observed as each configuration shows different emission colors, yellow for octahedral type and red for the trigonal prismatic one. PMID- 27264678 TI - Effects of inhomogeneity on triglyceride digestion of emulsions using an in vitro digestion model (Tiny TIM). AB - The colloidal behaviour and extent of lipolysis of various emulsions stabilized by whey protein and Tween were studied using the TNO Intestinal Model (TIM) extended with a purposely designed gastric compartment. The in vitro results suggest that creaming of a fatty layer in the gastric region causes a delay in fat entering the small intestinal region, delays and reduces the free fatty acid content in the small intestinal lumen and delays fat absorption. It was shown that controlling the pH with pig gastric juice instead of simulated gastric juice delayed creaming of the emulsions significantly, which resulted in faster gastric lipolysis. However, because the digestive conditions are not adjusted by physiological regulation mechanisms such as the regulation of gastric emptying by the detection of nutrients in the small intestine, care must be taken to translate these results to the in vivo reality. It is expected that the differences between the systems will be tempered by the physiological feedback regulation mechanisms of digestion. PMID- 27264679 TI - Nerve growth factor & TrkA as novel therapeutic targets in cancer. AB - In the past 20years, nerve growth factor (NGF) and its receptors TrkA & p75NTR were recognized to be overexpressed in the overwhelming majority of human solid cancers. Recent studies discovered the presence of overactive TrkA signaling due to TrkA rearrangements or TrkA fusion products in frequent cancers like colorectal cancer, thyroid cancer, or acute myeloid leukemia. Thus, targeting TrkA/NGF via selective small-molecule-inhibitors or antibodies has gained enormous attention in the drug discovery sector. Clinical studies on the anti cancer impact of NGF-blocking antibodies are likely to be accelerated after the recent removal of clinical holds on these agents by regulatory authorities. Based on these current developments, the present review provides not only a broad overview of the biological effects of NGF-TrkA-p75NTR on cancer cells and their microenvironment, but also explains why NGF and its receptors are going to evoke major interest as promising therapeutic anti-cancer targets in the coming decade. PMID- 27264680 TI - Influence of Constitution and Charge on Radical Pairing Interactions in Tris radical Tricationic Complexes. AB - The results of a systematic investigation of trisradical tricationic complexes formed between cyclobis(paraquat-p-phenylene) bisradical dicationic (CBPQT(2(*+))) rings and a series of 18 dumbbells, containing centrally located 4,4'-bipyridinium radical cationic (BIPY(*+)) units within oligomethylene chains terminated for the most part by charged 3,5-dimethylpyridinium (PY(+)) and/or neutral 3,5-dimethylphenyl (PH) groups, are reported. The complexes were obtained by treating equimolar amounts of the CBPQT(4+) ring and the dumbbells containing BIPY(2+) units with zinc dust in acetonitrile solutions. Whereas UV-Vis-NIR spectra revealed absorption bands centered on ca. 1100 nm with quite different intensities for the 1:1 complexes depending on the constitutions and charges on the dumbbells, titration experiments showed that the association constants (Ka) for complex formation vary over a wide range, from 800 M(-1) for the weakest to 180 000 M(-1) for the strongest. While Coulombic repulsions emanating from PY(+) groups located at the ends of some of the dumbbells undoubtedly contribute to the destabilization of the trisradical tricationic complexes, solid-state superstructures support the contention that those dumbbells with neutral PH groups at the ends of flexible and appropriately constituted links to the BIPY(*+) units stand to gain some additional stabilization from C-H...pi interactions between the CBPQT(2(*+)) rings and the PH termini on the dumbbells. The findings reported in this Article demonstrate how structural changes implemented remotely from the BIPY(*+) units influence their non-covalent bonding interactions with CBPQT(2(*+)) rings. Different secondary effects (Coulombic repulsions versus C-H...pi interactions) are uncovered, and their contributions to both binding strengths associated with trisradical interactions and the kinetics of associations and dissociations are discussed at some length, supported by extensive DFT calculations at the M06-D3 level. A fundamental understanding of molecular recognition in radical complexes has relevance when it comes to the design and synthesis of non-equilibrium systems. PMID- 27264681 TI - Risk factors for recurrence in stage II/III colorectal cancer patients treated with curative surgery: The impact of postoperative tumor markers and an infiltrative growth pattern. AB - BACKGROUND AND OBJECTIVES: We evaluated the capacity of clinicopathological factors to predict recurrence in stage II/III colorectal cancer (CRC) patients after curative resection. METHODS: We retrospectively examined 386 stage II/III CRC patients who underwent curative resections between April 2008 and August 2013. We assessed the predictive power of pre- and postoperative tumor marker levels, lymphatic and venous invasion, and infiltrative growth patterns using Cox's proportional hazards model. RESULTS: Of 206 stage II and 180 stage III patients, 26 (13%) and 46 (26%) patients, respectively, developed recurrences with median follow-up times of 51 and 45 months, respectively. Independent risk factors for recurrence were lymphatic invasion (hazard ratio [HR], 5.99; P = 0.0006) and infiltrative growth patterns (HR, 4.02; P = 0.017) in stage II patients; and elevated preoperative carcinoembryonic antigen levels (HR, 3.22; P = 0.004), elevated postoperative carbohydrate antigen 19-9 levels (HR, 5.08; P = 0.005), and infiltrative growth patterns (HR, 3.19; P = 0.037) in stage III patients. CONCLUSIONS: High-recurrence risk can be identified in stage II/III CRC patients by assessing perioperative serum tumor marker levels, lymphatic invasion, and infiltrative growth patterns. Intensive follow-up for patients with these risk factors may help detect recurrences promptly and improve survival. J. Surg. Oncol. 2016;114:368-374. (c) 2016 Wiley Periodicals, Inc. PMID- 27264682 TI - Skeletal fractures resulting from fatal falls: A review of the literature. AB - To investigate what is currently known about skeletal blunt force trauma (BFT) resulting from falls, and how valuable that research is in contributing to forensic anthropology investigations and interpretations of circumstances of death, a comprehensive review of forensic anthropology, forensic pathology and clinical medicine literature was performed. Forensic anthropology literature identified that establishing the type of fall from the analysis of BFT is difficult given the uniqueness of each fall event, the complexities involved with identify BFT and, in particular, the limited available research documenting fracture patterning and morphologies. Comparatively, skeletal BFT resulting from fatal falls is well documented in the forensic pathology and clinical medicine literature. These disciplines cover a wide range of fall types (free falls, falls in juveniles, specific fractures produced from falls, falls down staircases, falls resulting in impalements, and 'other' fall types), provide details on how the nature of the fall influences the skeletal fracturing, and documents the anatomical regions susceptible to fracturing. Whilst these contributions may assist forensic anthropologists, they provide limited details of fracture patterns and morphologies and thus further research investigating the details of skeletal BFT resulting from fatal falls is required. PMID- 27264683 TI - New prediction models for dental age estimation in Thai children and adolescents. AB - The aims of this study were to develop new prediction models for dental age estimation and to test the accuracy of the resulting models in comparison with the Demirjian et al. and the Willems et al. methods in Thai children and adolescents. Digital panoramic radiographs of 1,134 Thai individuals (487 males and 647 females) aged from 6 to 15 years were selected and evaluated for dental age estimation. Quadratic regression was used to generate new models. The results showed that the new prediction models indicated a strong correlation coefficient between the dental maturity score and the chronological age in both sexes (r=0.951 for males, r=0.945 for females). The new age prediction models were: y=0.006297x(2) - 0.804930x+32.591843 for males and y=0.010677x(2) - 1.538823x+61.955056 for females, where y is the dental age, x is the dental maturity score according to Demirjian et al. METHOD: Moreover, these new models were tested showing the greatest accuracy for estimating the age in Thai samples using the mean difference values between the dental and the chronological ages ( 0.04 years for males, 0.02 years for females) when compared with the Demirjian et al. and the Willems et al. METHODS: In addition, the new models revealed a high percentage of accuracy in the absolute difference values between the dental and the chronological ages within 1 year (76.26% and 74.49% for males and females, respectively). Furthermore, our results in mean difference values indicated that the Demirjian et al. method (0.11 and 0.10 years for males and females, respectively) was more accurate than the Willems et al. method (-0.37 and -0.39 years for males and females, respectively) in Thai samples. In conclusion, the new age prediction models in this study provide accurate age estimation in both sexes, suggesting that these models be applied for forensic age estimation, especially in Thai children and adolescents. PMID- 27264684 TI - Multivariate methods for the analysis of complex and big data in forensic sciences. Application to age estimation in living persons. AB - Researchers handle increasingly higher dimensional datasets, with many variables to explore. Such datasets pose several problems, since they are difficult to handle and present unexpected features. As dimensionality increases, classical statistical analysis becomes inoperative. Variables can present redundancy, and the reduction of dataset dimensionality to its lowest possible value is often needed. Principal components analysis (PCA) has proven useful to reduce dimensionality but present several shortcomings. As others, forensic sciences will face the issues specific related to an evergrowing quantity of data to be integrated. Age estimation in living persons, an unsolved problem so far, could benefit from the integration of various sources of data, e.g., clinical, dental and radiological data. We present here novel multivariate techniques (nonlinear dimensionality reduction techniques, NLDR), applied to a theoretical example. Results were compared to those of PCA. NLDR techniques were then applied to clinical, dental and radiological data (13 variables) used for age estimation. The correlation dimension of these data was estimated. NLDR techniques outperformed PCA results. They showed that two living persons sharing similar characteristics may present rather different estimated ages. Moreover, data presented a very high informational redundancy, i.e., a correlation dimension of 2. NLDR techniques should be used with or preferred to PCA techniques to analyze complex and big data. Data routinely used for age estimation may not be considered suitable for this purpose. How integrating other data or approaches could improve age estimation in living persons is still uncertain. PMID- 27264685 TI - NK cell education via nonclassical MHC and non-MHC ligands. AB - Natural killer (NK) cell education, a process for achieving functional maturation and self-tolerance, has been previously defined by the interaction between self major histocompatibility complex class I (MHC-I) molecules and their specific inhibitory receptors. Over the past several years, growing evidence has highlighted the important roles of nonclassical MHC-I and non-MHC-I molecules in NK cell education. Herein, we review the current knowledge of NK cell education, with a particular focus on nonclassical MHC-I- and non-MHC-I-dependent education, and compare them with the classical MHC-I-dependent education theory. In addition, we update and extend this theory by presenting the 'Confining Model', discussing cis and trans characteristics, reassessing quantity and quality control, and elucidating the redundancy of NK cell education in tumor and virus infection. PMID- 27264688 TI - Exosomes: multitask cargo carriers modulating innate immunity to viruses. PMID- 27264687 TI - Novel exosome-targeted T-cell-based vaccine counteracts T-cell anergy and converts CTL exhaustion in chronic infection via CD40L signaling through the mTORC1 pathway. AB - CD8+ cytotoxic T lymphocyte (CTL) exhaustion is a chief issue for ineffective virus elimination in chronic infectious diseases. We generated novel ovalbumin (OVA)-specific OVA-Texo and HIV-specific Gag-Texo vaccines inducing therapeutic immunity. To assess their therapeutic effect in chronic infection, we developed a new chronic infection model by i.v. infecting C57BL/6 mice with the OVA expressing adenovirus AdVova. During chronic AdVova infection, mouse CTLs were found to express the inhibitory molecules programmed cell-death protein-1 (PD-1) and lymphocyte-activation gene-3 (LAG-3) and to be functionally exhausted, showing a significant deficiency in T-cell proliferation, IFN-gamma production and cytolytic effects. Naive CD8+ T cells upregulated inhibitory PD-ligand 1 (PD L1), B- and T-lymphocyte attenuator and T-cell anergy-associated molecules (Grail and Itch) while down-regulating the proliferative response upon stimulation in mice with chronic infection. Remarkably, the OVA-Texo vaccine counteracted T-cell anergy and converted CTL exhaustion. The latter was associated with (i) the upregulation of a marker for CTL functionality, diacetylated histone-H3 (diAcH3), (ii) a fourfold increase in CTLs, occurring independent of host DCs or CD4+ T cells, and (iii) the restoration of CTL IFN-gamma production and cytotoxicity. In vivo OVA-Texo-stimulated CTLs upregulated the activities of the mTORC1 pathway related molecules Akt, S6, eIF4E and T-bet, and treatment of the CTLs with an mTORC1 inhibitor, rapamycin, significantly reduced the OVA-Texo-induced increase in CTLs. Interestingly, OVA-Texo-mediated CD40L signaling played a critical role in the observed immunological effects. Importantly, the Gag-Texo vaccine induced Gag-specific therapeutic immunity in chronic infection. Therefore, this study should have a serious impact on the development of new therapeutic vaccines for human immunodeficiency virus (HIV-1) infection. PMID- 27264690 TI - Factors influencing a nurse's decision to question medication administration in a neonatal clinical care unit. AB - AIMS AND OBJECTIVES: The aim of this study was to identify factors that influence nurse's decisions to question concerning aspects of medication administration within the context of a neonatal clinical care unit. BACKGROUND: Medication error in the neonatal setting can be high with this particularly vulnerable population. As the care giver responsible for medication administration, nurses are deemed accountable for most errors. However, they are recognised as the forefront of prevention. Minimal evidence is available around reasoning, decision making and questioning around medication administration. Therefore, this study focuses upon addressing the gap in knowledge around what nurses believe influences their decision to question. DESIGN: A critical incident design was employed where nurses were asked to describe clinical incidents around their decision to question a medication issue. Nurses were recruited from a neonatal clinical care unit and participated in an individual digitally recorded interview. RESULTS: One hundred and three nurses participated between December 2013-August 2014. Use of the constant comparative method revealed commonalities within transcripts. Thirty six categories were grouped into three major themes: 'Working environment', 'Doing the right thing' and 'Knowledge about medications'. CONCLUSIONS: Findings highlight factors that influence nurses' decision to question issues around medication administration. Nurses feel it is their responsibility to do the right thing and speak up for their vulnerable patients to enhance patient safety. Negative dimensions within the themes will inform planning of educational strategies to improve patient safety, whereas positive dimensions must be reinforced within the multidisciplinary team. RELEVANCE TO CLINICAL PRACTICE: The working environment must support nurses to question and ultimately provide safe patient care. Clear and up to date policies, formal and informal education, role modelling by senior nurses, effective use of communication skills and a team approach can facilitate nurses to appropriately question aspects around medication administration. PMID- 27264689 TI - Intravenous immunoglobulin replacement treatment does not alter polymorphonuclear leukocytes function and surface receptors expression in patients with common variable immunodeficiency. AB - The study of the expression of CD16, CD11b and Siglec 9 receptors and the oxidative burst provides insights on polymorphonuclear leukocytes (PMN) functionality in common variable immunodeficiency (CVID) and on the possible effects of intravenous immunoglobulin (IVIg) infusion. We evaluated in vivo before and soon after IVIg administration the CD16, CD11b and Siglec 9 expression on unstimulated and Escherichia coli-stimulated PMN and the oxidative burst induced by Escherichia coli and PMA. The E. coli stimulation up-regulated CD16 and Siglec 9 expression and it induced a strong CD11b up-regulation at baseline and soon after IVIg. The oxidative burst overlapped that observed in healthy donors when induced by Escherichia coli while it increased when induced by PMA. Soon after IVIg infusion, the oxidative burst decreased only when induced by PMA. Our results showed that the IVIg infusion in vivo had a minimal effect on CVID's PMN. PMID- 27264691 TI - Psychometric testing of a person-centred care scale the Eden Warmth Survey in a long-term care home in New Zealand. AB - BACKGROUND: Traditional nursing homes have been viewed as dominated by the medical model. Since the 1990s, the Eden Alternative(TM) has become a significant model in systemic transformations in nursing homes. The purpose of this study was to evaluate the psychometric performance of the 20 items of the Eden Warmth Survey - Residents (EWS-R) in an aged-care home. DESIGN: A resident's satisfaction survey was used to collect a sample of 85 long-term care home residents. METHODS: Psychometric evaluation included item analyses, reliability including internal consistency and stability, criterion-related validity and construct validity. RESULTS: The reduced 13 items demonstrated adequate reliability (alpha = 0.82) with two factors, Trust and Connectedness with Others and Care Practices, extracted and contributed to 57.9% of the total variance. CONCLUSIONS: The 13-item of EWS-R can be considered as a reliable and predictive scale for assessing quality of life and overall satisfaction on people living in long-term care facilities. PMID- 27264694 TI - Radiation dermatitis caused by a bolus effect from an abdominal compression device. AB - American Association of Physicists in Medicine (AAPM) Task Group 176 evaluated the dosimetric effects caused by couch tops and immobilization devices. The report analyzed the extensive physics-based literature on couch tops, stereotactic body radiation therapy (SBRT) frames, and body immobilization bags, while noting the scarcity of clinical reports of skin toxicity because of external devices. Here, we present a clinical case report of grade 1 abdominal skin toxicity owing to an abdominal compression device. We discuss the dosimetric implications of the utilized treatment plan as well as post hoc alternative plans and quantify differences in attenuation and skin dose/build-up between the device, a lower-density alternative device, and an open field. The description of the case includes a 66-year-old male with HER2 amplified poorly differentiated distal esophageal adenocarcinoma treated with neoadjuvant chemo-radiation and the use of an abdominal compression device. Radiation was delivered using volumetric modulated arc therapy (VMAT) with 2 arcs using abdominal compression and image guidance. The total dose was 50.4Gy delivered over 40 elapsed days. With 2 fractions remaining, the patient developed dermatitis in the area of the compression device. The original treatment plan did not include a contour of the device. Alternative post hoc treatment plans were generated, one to contour the device and a second with anterior avoidance. In conclusion, replanning with the device contoured revealed the bolus effect. The skin dose increased from 27 to 36Gy. planned target volume (PTV) coverage at 45Gy was reduced to 76.5% from 95.8%. The second VMAT treatment plan with an anterior avoidance sector and more oblique beam angles maintained PTV coverage and spared the anterior wall, however at the expense of substantially increased dose to lung. This case report provides an important reminder of the bolus effect from external devices such as abdominal compression. Special consideration must be given to contour and/or avoiding beam entrance to the device, and to the use of such devices in patients who may have heightened radiosensitivity, such as those who are human immunodeficiency virus (HIV)-positive. PMID- 27264686 TI - Clash of the Cytokine Titans: counter-regulation of interleukin-1 and type I interferon-mediated inflammatory responses. AB - Over the past decades the notion of 'inflammation' has been extended beyond the original hallmarks of rubor (redness), calor (heat), tumor (swelling) and dolor (pain) described by Celsus. We have gained a more detailed understanding of the cellular players and molecular mediators of inflammation which is now being applied and extended to areas of biomedical research such as cancer, obesity, heart disease, metabolism, auto-inflammatory disorders, autoimmunity and infectious diseases. Innate cytokines are often central components of inflammatory responses. Here, we discuss how the type I interferon and interleukin-1 cytokine pathways represent distinct and specialized categories of inflammatory responses and how these key mediators of inflammation counter regulate each other. PMID- 27264695 TI - Nursing expertise: a course of ambiguity and evolution in a concept. AB - In this article, we clarify and describe the nature of nursing expertise and provide a framework to guide its identification and further development. To have utility and rigour, concept-driven research and theories of practice require underlying concepts that are robust, valid and reliable. Advancing understanding of a concept requires careful attention to explicating its knowledge, metaphors and conceptual meaning. Examining the concepts and metaphors of nursing expertise, and how they have been interpreted into the nursing discourse, we aimed to synthesise definitions and similarities between concepts and elicit the defining characteristics and properties of nursing expertise. In clarifying the concept, we sought to move beyond the ambiguity that currently surrounds expertise in nursing and unravel it to make explicit the characteristics of nursing expertise from published peer-reviewed studies and structured literature synthesis. Findings indicate a lack of clarity surrounding the use of the term expertise. Traditional reliance upon intuition as a way of explaining expert performance is slowly evolving. Emerging from the analysis is a picture of expertise as the relationship between networks of contextual reasoning, understanding and practice. Striking absences in the discourse include limited explication of ethical reasoning and theorising a broader interpretation of expertise reflective of contemporary forms of nursing. PMID- 27264697 TI - Case of pityriasis rubra pilaris with annular pattern as an early manifestation. PMID- 27264696 TI - Shedding light on Aspergillus niger volatile exometabolome. AB - An in-depth exploration of the headspace content of Aspergillus niger cultures was performed upon different growth conditions, using a methodology based on advanced multidimensional gas chromatography. This volatile fraction comprises 428 putatively identified compounds distributed over several chemical families, being the major ones hydrocarbons, alcohols, esters, ketones and aldehydes. These metabolites may be related with different metabolic pathways, such as amino acid metabolism, biosynthesis and metabolism of fatty acids, degradation of aromatic compounds, mono and sesquiterpenoid synthesis and carotenoid cleavage. The A. niger molecular biomarkers pattern was established, comprising the 44 metabolites present in all studied conditions. This pattern was successfully used to distinguish A. niger from other fungi (Candida albicans and Penicillium chrysogenum) with 3 days of growth by using Partial Least Squares-Discriminant Analysis (PLS-DA). In addition, PLS-DA-Variable Importance in Projection was applied to highlight the metabolites playing major roles in fungi distinction; decreasing the initial dataset to only 16 metabolites. The data pre-processing time was substantially reduced, and an improvement of quality-of-fit value was achieved. This study goes a step further on A. niger metabolome construction and A. niger future detection may be proposed based on this molecular biomarkers pattern. PMID- 27264698 TI - Restructuring of the sponge microbiome favors tolerance to ocean acidification. AB - Ocean acidification is increasing and affects many marine organisms. However, certain sponge species can withstand low-pH conditions. This may be related to their complex association with microbes. We hypothesized that species with greater microbial diversity may develop functional redundancy that could enable the holobiont to survive even if particular microbes are lost at low-pH conditions. We evaluated the effects of acidification on the growth and associated microbes of three ubiquitous Mediterranean sponges by exposing them to the present pH level and that predicted for the year 2100. We found marked differences among the species in the acquisition of new microbes, being high in Dysidea avara, moderate in Agelas oroides and null in Chondrosia reniformis; however, we did not observe variation in the overall microbiome abundance, richness or diversity. The relative abilities to alter the microbiomes contributes to survivorship in an OA scenario as demonstrated by lowered pH severely affecting the growth of C. reniformis, halving that of A. oroides, and unaffecting D. avara. Our results indicate that functional stability of the sponge holobiont to withstand future OA is species-specific and is linked to the species' ability to use horizontal transmission to modify the associated microbiome to adapt to environmental change. PMID- 27264699 TI - Effect of bamboo and rice straw biochars on the mobility and redistribution of heavy metals (Cd, Cu, Pb and Zn) in contaminated soil. AB - Biochar has emerged as an efficient tool to affect bioavailability of heavy metals in contaminated soils. Although partially understood, a carefully designed incubation experiment was performed to examine the effect of biochar on mobility and redistribution of Cd, Cu, Pb and Zn in a sandy loam soil collected from the surroundings of a copper smelter. Bamboo and rice straw biochars with different mesh sizes (<0.25 mm and <1 mm), were applied at three rates (0, 1, and 5% w/w). Heavy metal concentrations in pore water were determined after extraction with 0.01 M CaCl2. Phytoavailable metals were extracted using DTPA/TEA (pH 7.3). The European Union Bureau of Reference (EUBCR) sequential extraction procedure was adopted to determine metal partitioning and redistribution of heavy metals. Results showed that CaCl2-and DTPA-extractable Cd, Cu, Pb and Zn concentrations were significantly (p < 0.05) lower in the bamboo and rice straw biochar treated soils, especially at 5% application rate, than those in the unamended soil. Soil pH values were significantly correlated with CaCl2-extractable metal concentrations (p < 0.01). The EUBCR sequential extraction procedure revealed that the acid extractable fractions of Cd, Cu, Pb and Zn decreased significantly (p < 0.05) with biochar addition. Rice straw biochar was more effective than bamboo biochar in decreasing the acid extractable metal fractions, and the effect was more pronounced with increasing biochar application rate. The effect of biochar particle size on extractable metal concentrations was not consistent. The 5% rice straw biochar treatment reduced the DTPA-extractable metal concentrations in the order of Cd < Cu < Pb < Zn, and reduced the acid extractable pool of Cd, Cu, Pb and Zn by 11, 17, 34 and 6%, respectively, compared to the control. In the same 5% rice straw biochar treatments, the organic bound fraction increased by 37, 58, 68 and 18% for Cd, Cu, Pb and Zn, respectively, compared to the control, indicating that the immobilized metals were mainly bound in the soil organic matter fraction. The results demonstrated that the rice straw biochar can effectively immobilize heavy metals, thereby reducing their mobility and bioavailability in contaminated soils. PMID- 27264701 TI - Flexivirga endophytica sp. nov., an endophytic actinobacterium isolated from a leaf of Sweet Basil. AB - A Gram-reaction-positive, aerobic, non-motile, irregular coccoid strain, designated YIM 7505T, was isolated from a leaf of Sweet Basil. Phylogenetic analysis on the basis of 16S rRNA gene sequence comparisons revealed that strain YIM 7505T was closely related to Flexivirga alba NBRC 107580T (98.9 % 16S rRNA gene sequence similarity) and formed a robust clade with F. alba NBRC 107580T in the neighbour-joining tree. Optimum growth of strain YIM 7505T was observed at 28 35 degrees C, pH 7.0 and in the presence of 0-3.0 % NaCl (w/v). The chemotaxonomic profiles of the strain comprised of anteiso-C16 : 0 as the major cellular fatty acid and MK-8(H4) as the respiratory menaquinone. The peptidoglycan of strain YIM 7505T contained serine, alanine, glycine, glutamic acid and lysine. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, six unidentified phospholipids, four unidentified glycolipids, an unidentified aminolipid and an unidentified aminophospholipid. The G+C contents of the genomic DNA of strain YIM 7505T was 66.7 mol%. DNA-DNA hybridizations of strain YIM 7505T with F. alba NBRC 107580T gave relatedness values of 50.6+/-2.2 %. On the basis of the data recorded from the present study, strain YIM 7505T is considered to represent a novel species of the genus Flexivirga, for which the name Flexivirga endophytica sp. nov. is proposed. The type strain is YIM 7505T (=KCTC 39536T=CGMCC 1.15085T). PMID- 27264702 TI - Hepatic complications of allogeneic hematopoietic cell transplantation. AB - Hepatic complications of allogeneic hematopoietic cell transplantation contribute substantially to the overall success of the procedure and represent a major cause of morbidity and mortality. Early hepatic complications consist of the sinusoidal obstruction syndrome, drug toxicities, infections, acute graft-versus-host disease, while late hepatic complications consist of chronic graft-versus host disease, chronic viral hepatitis, and iron overload states. Successful management of the hepatic complications of allogeneic hematopoietic cell transplantation is dependent on several factors. These include the recognition and elimination of any pre-transplant risk factors for these problems and the development of strategies to evaluate and prevent them in both the early and later posttransplant periods. The aims of present review are 1) to identify the early and late hepatic complications of allogeneic hematopoietic cell transplantation, in the chronological order at which they occur, 2) to characterize the diagnostic procedures used to identify them, and finally 3) to present the current therapeutic approaches used to manage these problems. PMID- 27264700 TI - Heterogeneity in readouts of canonical wnt pathway activity within intestinal crypts. AB - BACKGROUND: Canonical Wnt pathway signaling is necessary for maintaining the proliferative capacity of mammalian intestinal crypt base columnar stem cells (CBCs). Furthermore, dysregulation of the Wnt pathway is a major contributor to disease, including oncogenic transformation of the intestinal epithelium. Given the critical importance of this pathway, numerous tools have been used as proxy measures for Wnt pathway activity, yet the relationship between Wnt target gene expression and reporter allele activity within individual cells at the crypt base remains unclear. RESULTS: Here, we describe a novel Axin2-CreERT2-tdTomato allele that efficiently marks both Wnt(High) CBCs and radioresistant reserve intestinal stem cells. We analyze the molecular and functional identity of Axin2-CreERT2 tdTomato-marked cells using single cell gene expression profiling and tissue regeneration assays and find that Axin2 reporter activity does not necessarily correlate with expression of Wnt target genes and, furthermore, that Wnt target genes themselves vary in their expression patterns at the crypt base. CONCLUSIONS: Wnt target genes and reporter alleles can vary greatly in their cell type specificity, demonstrating that these proxies cannot be used interchangeably. Furthermore, Axin2-CreERT2-tdTomato is a robust marker of both active and reserve intestinal stem cells and is thus useful for understanding the intestinal stem cell compartment. Developmental Dynamics 245:822-833, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27264703 TI - Minimal Residual Disease (MRD) Detection with Translocations and T-Cell Receptor and Immunoglobulin Gene Rearrangements in Adult Acute Lymphoblastic Leukaemia Patients: A Pilot Study. AB - Monitoring minimal residual disease has become increasingly important in clinical practice of ALL management. Break-point fusion regions of leukaemia related chromosomal aberrations and rearranged immunoglobulin (Ig) and T cell-receptor (TCR) genes, which can be detected by polymerase chain reaction (PCR), are used as leukaemia specific markers in genetic studies of MRD. A total of 31 consecutive patients with newly diagnosed ALL were screened for eligibility criteria. Of those 26 were included in the study. One patient with partial response following induction therapy and four patients who were lost to follow-up after induction were excluded from the study; thus 21 patients were evaluated for MRD. Chromosomal aberrations were detected in 5 (24%) of the patients and were used for MRD monitoring. Three patients had t(9;22) translocation, the other 2 had t(4;11) and t(1;19). MRD-based risk stratification of the 16 patients analysed for Ig/TCR rearrangements revealed 3 low-risk, 11 intermediate-risk and 2 high-risk patients. MRD monitoring is progressively getting to be a more important predictive factor in adult ALL patients. As reported by others confirmed by our limited data there is a good correlation between MRD status and clinical outcome in patients receiving chemotherapy. The pilot-study presented here is the first that systematically and consecutively performs a molecular MRD monitoring of ALL patients in Turkey. PMID- 27264704 TI - Protein Z G79A polymorphism in Turkish pediatriccerebral infarct patients. AB - Protein Z (PZ) plays an enhancer role in coagulation as an anticoagulant. This is the first study in which G79A polymorphism investigated in Turkish paediatric stroke patients. Ninety-one paediatric stroke patients with cerebral ischemia and 70 control subjects were analyzed for PZ G79A and also FVL, PT mutations. PZ 79 'A' allele in homozygous state was found in five patients (5,5%), while it was found only in one control subject (1,4%) and it was seemed as a risk factor for peadiatric ischemia [OR=3,94 (0,44-35,1)]. When patients and controls who had FVL and PT carriers were excluded, AA genotype carried a risk [OR=3,88 (0,41-36,5)]. Also plasma protein Z levels measured in 21 stroke patients and 52 controls. Plasma protein Z levels were not different between stroke patients (500,95 ngmL 1+/-158,35) and controls (447,34 ngmL-1+/-165,97). But the plasma levels of protein Z was decreased in patients with AA genotype. Our data showed that carrying 79 AA genotype could be a genetic risk factor for cerebral infarct in peadiatric patients. PMID- 27264705 TI - Insulin-like growth factor-1 levels in children with Beta-thalassemia minor. AB - OBJECTIVE: Growth retardation in children with b-thalassemia major is multifactorial. Some etiologies described for this condition are hemochromatosis, disturbed growth hormone (GH) / insulin growth factor-1 (IGF-1) axis, undernutrition and hypermetabolism. It has also been proven that growth retardation is present in b-thalassemia major children despite regular transfusion and chelation. Our aim was to evaluate the level of IGF-1 in b thalassemia minor subjects and compare it with that in healthy children. METHODS: Fifty children aged 6 months to 15 years with b-thalassemia minor (32 males, 18 females) and 50 age- and sex-matched normal healthy children were selected. Medical history was taken and complete physical examination was done in each case; IGF-1 level was checked in all cases. This study was done in Shiraz, southern Iran, during 2005. RESULTS: IGF-1 levels were significantly lower in b thalassemia minor children than normal children (P = 0.015). This result demonstrates that some etiologies of growth failure in b-thalassemia major other than those described to date can exist, which may be shared with b-thalassemia minor in feature or may be transformed by genes that are either expressed or not. CONCLUSION: We conclude that in addition to that observed in b-thalassemia major, IGF-1 level is also decreased in b-thalassemia minor, and these two may have similar etiologies. PMID- 27264706 TI - Hematological disorders in 6-hydroxydopamine-induced rat model of Parkinson's disease. AB - OBJECTIVE: The present work was undertaken in order to investigate the effects of right-unilateral lesion of substantia nigra neurons by means of 6- hydroxydopamine (6-OHDA), a dopaminergic-selective neurotoxin, on hematological parameters in rats. The primary reason for the using of rat model of Parkinson's disease was the interest regarding the role of the central dopaminergic system in hematopoiesis regulation because some neurological diseases like Parkinson's disease are well-correlated with anemia associated with autonomic dysfunction in rats. METHODS: Thirty male Wistar rats weighing 200 +/- 50 g at the start of the experiment were used. The substantia nigra was right-unilateral lesioned by stereotaxic microinjections of 8 micrograms (free base) 6-OHDA, dissolved in 4 ul physiological saline containing 0.1% ascorbic acid, administered through the Hamilton microsyringe over 4.50 minutes. 7 days after neurosurgery, we assessed the total number of white blood cells (WBC), the total number of red blood cells (RBC), hemoglobin level and the erythrocyte indexes (mean cell volume, MCV and mean cell hemoglobin, MCH). Hematological parameters were assayed by a COULTER(r) Ac?T 5diff CP-precision instruments for hematology research. RESULTS: 6-OHDA treatment induced a significantly decrease of white blood cells (p<0.03), red blood cells (p<0.01), hemoglobin level (p<0.02) comparative with sham-operated rats. By contrast, in the 6-OHDA-lesioned rats the erythrocyte indexes (mean cell volume, MCV (p<0.04); mean cell hemoglobin, MCH (p<0.01)) were significantly enhanced comparative with sham-operated rats. CONCLUSION: On the whole, the obtained data indicate the important role of the central dopaminergic system in the regulation of erythrocyte dynamics. PMID- 27264707 TI - Immunohematological characteristics of Nigerian sickle cell disease patients with osteomyelitis. AB - OBJECTIVE: We aimed in this paper to investigate some immunohematological characteristics of Nigerian sickle cell anemia (SCA) patients with osteomyelitis. METHODS: Thirty SCA patients with osteomyelitis (SO) and 30 SCA patients without osteomyelitis (S) were investigated. The PCV, WBC and platelet count were done on automated counter, while the erytorocyte sedimentation rate (ESR) was determined by Westergren's technique. C3 activator, C1-INH, IgA, IgG and IgM were estimated by the single radial immunodiffusion method. RESULTS: The SO patients weighed less (z =1.943, p<0.055) and were shorter (z = -2.064, p<0.039). High serum levels of IgG, IgM, C1-INH and C3 activator were also found in the SO group. ESR correlated positively with hematocrit (r=0.371, p<0.04) and C3 activator (r=0.468, p<0.03) in SO. Similarly, WBC correlated positively with C1-INH (r=0.806, p<0.01), while we also noted positive correlation between C1-INH and C3 activator (r=0.525, p<0.02). In SO, ESR correlated positively with both IgM (r=0.531, p<0.02) and C3 activator (r=0.449, p<0.05). CONCLUSION: This study suggests some derangement in immune status in Nigerian SCA patients with osteomyelitis and that C1-INH and C3 activator may be useful markers of immune status in SCA patients. PMID- 27264708 TI - De-novo CD5 + B- prolymphocytic leukemia (PLL) presenting at younger age with favourable outcome. AB - B-cell prolymphocytic leukemia (B-PLL) comprises 1% of chronic lymphocytic leukemias. CD5 positivity is seen in 1/3rd of cases which generally arise from pre existing CLL. They have longer median survival compared with de novo B-PLL which are commonly CD5 negative and are more aggressive with an older age of presentation. Herewith, we describe a 48-year-old male of de-novo CD5+ B-PLL presenting with minimal lymphadenopathy and massive splenomegaly with 90% atypical lymphoid cells in the peripheral smear and bone marrow. Immunophenotyping was strongly positive for CD5, CD45, CD19, CD22, FMC-7, S-Ig and CD38, moderately positive for CD 11c, weakly positive for CD23 and negative for CD-103 and ZAP 70. The patient responded well to fludarabine and cyclophosphamide and had an uneventful hospital course. Our case illustrates a de novo B-PLL with aberrant CD5 positivity who had a short duration of illness, younger age at presentation and favourable treatment outcome. PMID- 27264709 TI - A childhood acute lymphoblastic leukemia (ALL) case with t(3;17)(q23;p13),t(5;12)(q31;p13),inv(11)(p15q12). AB - It is known that clonal chromosomal changes in childhood ALL are nonrandom and important markers for diagnosis, prognosis and relaps. In this report we present 4 year-old boy with ALL-L1 who has complex chromosomal rearrangements. Chromosome analysis was performed on bone marrow aspiration sample in relaps after one year from diagnosis and induction chemotherapy. The karyotype was; 46,XY,t(3;17)(q23;p13),t(5;12)(q31;p13),inv(11)(p15q12) [11]/46,XY[8]. PMID- 27264710 TI - A case of adult acute T-cell lymphoblastic leukemia presented with hemophagocytic syndrome. PMID- 27264711 TI - Chronic Myeloid Leukemia Associated With Signet-Ringed Adenocarcinoma of Stomach And Review Of The Literature. PMID- 27264713 TI - A case of multiple myeloma with double malarial infection. PMID- 27264712 TI - Author Reply. PMID- 27264714 TI - Identification of potent maturation inhibitors against HIV-1 clade C. AB - Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR). The first-in-class maturation inhibitor bevirimat (BVM) failed against a subset of HIV-1 isolates in clinical trials due to polymorphisms present in the CA-SP1 region of the Gag protein. Sequence analysis indicated that these polymorphisms are more common in non-clade B strains of HIV-1 such as HIV-1 clade C. Indeed, BVM was found to be ineffective against HIV-1 clade C molecular clones tested in this study. A number of BVM analogs were synthesized by chemical modifications at the C-28 position to improve its activity. The new BVM analogs displayed potent activity against HIV-1 clade B and C and also reduced infectivity of the virus. This study identifies novel and broadly active BVM analogs that may ultimately demonstrate efficacy in the clinic. PMID- 27264715 TI - Thermographic mapping of the skin surface in biometric evaluation of cellulite treatment effectiveness. AB - BACKGROUND: Cellulite is one of the worst tolerated aesthetic imperfections. Edema that accompanies cellulite causes disorders of blood flow what may be observed as changes in the skin surface temperature. The aim of this paper was to develop a new method based on the analysis and processing of thermal images of the skin for biometric evaluation of severity of cellulite and monitoring its treatment. METHODS: The observations of the treatment effects were conducted on 10 females (33.4 +/- 6.4 years). Thermal images of the volunteers' thighs were captured before starting the therapy (T0 ). In the following stages: T1 , T2 , and T3 , thermal images were captured 2 weeks after the first, second and third Alidya treatment administration, respectively. Profiled algorithms were developed to determine the mean Grey Level Co-occurrence Matrix (GLCM) contrast in the acquired thermograms. RESULTS: The mean GLCM contrast for the phase T0 was 70.91, and for the stages T1 , T2 , and T3 : 57.78, 41.80, and 38.53, respectively. CONCLUSION: The use of proposed method (GLCM contrast) enables biometric evaluation of the effectiveness of cellulite treatment. Traditionally used parameters of infrared analysis such as local points of the maximum and minimum temperature or the median temperatures are not useful in thermal, biometric evaluation of anti-cellulite preparations. PMID- 27264716 TI - Evaluation of the tablets' surface flow velocities in pan coaters. AB - The tablet pan coating process involves various types of transverse tablet bed motions, ranging from rolling to cascading. To preserve satisfactory results in terms of coating quality after scale-up, understanding the dynamics of pan coating process should be achieved. The aim of this study was to establish a methodology of estimating translational surface velocities of the tablets in a pan coater and to assess their dependence on the drum's filling degree, the pan speed, the presence of baffles and the selected tablet properties in a dry bed system and during coating while varying the drum's filling degree and the pan speed. Experiments were conducted on the laboratory scale and on the pilot scale in side-vented pan coaters. Surface movement of biconvex two-layer tablets was assessed before, during and after the process of active coating. In order to determine the tablets' surface flow velocities, a high-speed video of the tablet surface flow was recorded via a borescope inserted into the coating drum and analysed via a cross-correlation algorithm. The obtained tablet velocity data were arranged in a linear fashion as a function of the coating drum's radius and frequency. Velocity data obtained during coating were close to those of dry tablets after coating. The filling degree had little influence on the tablet velocity profile in a coating drum with baffles but clearly affected it in a coating drum without baffles. In most but not all cases, tablets with a lower static angle of repose had tablet velocity profiles with lower slopes than tablets with higher inter-tablet friction. This particular tablet velocity response can be explained by case specific values of tablet bed's dynamic angle of repose. PMID- 27264717 TI - Anti-cancer activity of doxorubicin-loaded liposomes co-modified with transferrin and folic acid. AB - Cancer-specific drug delivery represents an attractive approach to prevent undesirable side-effects and increase the accumulation of the drug in the tumor. Surface modification of nanoparticles such as liposomes with targeting moieties specific to the up-regulated receptors on the surface of tumor cells thus represents an effective strategy. Furthermore, since this receptor expression can be heterogeneous, using a dual-combination of targeting moieties may prove advantageous. With this in mind, the anti-cancer activity of PEGylated doxorubicin-loaded liposomes targeted with folic acid (F), transferrin (Tf) or both (F+Tf) was evaluated. The dual-targeted liposomes showed a 7-fold increase in cell association compared to either of the single-ligand targeted ones in human cervical carcinoma (HeLa) cell monolayers. The increased penetration and cell association of the dual-targeted liposomes were also demonstrated using HeLa cell spheroids. The in vitro cytotoxicity of the doxorubicin liposomes (LD) was then evaluated using HeLa and A2780-ADR ovarian carcinoma cell monolayers. In both these cell lines, the (F+Tf) LD showed significantly higher cytotoxic effects than the untargeted, or single-ligand targeted liposomes. In a HeLa xenograft model in nude mice, compared to the untreated group, though the untargeted LD showed 42% tumor growth inhibition, both the (F) LD and (F+Tf) LD showed 75% and 79% tumor growth inhibition respectively. These results thus highlight that though the dual-targeted liposomes represent an effective cytotoxic formulation in the in vitro setting, they were equally effective as the folic acid-targeted liposomes in reducing tumor burden in the more complex in vivo setting in this particular model. PMID- 27264718 TI - PPARG gene C161T CT/TT associated with lower blood lipid levels and ischemic stroke from large-artery atherosclerosis in a Han population in Guangdong. AB - OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARG) is a transcription factor involved in atherosclerosis and related diseases. In this study, we aimed to investigate whether PPARG C161T was associated with lipid levels and large-artery atherosclerosis (LAA) ischemic stroke in a Han Chinese population in Guangdong province. METHODS: The genotype PPARG C161T in 149 LAA ischemic stroke patients and 125 healthy controls was examined by polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Associations with LAA ischemic stroke were analyzed for PPARG C161T genotype, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and a logistic regression analysis was performed to identify risk factors for LAA ischemic stroke. RESULTS: The frequency of CC was higher than that of CT + TT and was significantly associated with LAA ischemic stroke. In both the LAA and control groups, TC and LDL-C levels were significantly higher in the CC type than the CT + TT, but TG and HDL-C levels were comparable. The only verified independent risk factors for LAA ischemic stroke were ischemic heart disease (OR: 2.784, 95% CI: 1.377-5.632; p = 0.004) and systolic blood pressure (OR: 1.014, 95% CI: 1.001 1.026; p = 0.029); the PPARG C161T allele was not independently associated with an increased risk of LAA ischemic stroke (OR = 0.697, 95% CI: 0.372-1.305; p = 0.260). CONCLUSION: In this Han population, PPARG C161T CT/TT was associated with LAA ischemic stroke and lower levels of blood TC and LDL-C, but was not an independent risk factor for LAA ischemic stroke. PMID- 27264719 TI - SIRT2 mediates NADH-induced increases in Nrf2, GCL, and glutathione by modulating Akt phosphorylation in PC12 cells. AB - SIRT2 plays important roles in multiple biological processes. It is unclear whether SIRT2 affects antioxidant capacity by modulating Nrf2, a key transcription factor for multiple antioxidant genes. By studying NADH-treated differentiated PC12 cells, we found that NADH induced a significant increase in the nuclear Nrf2, which was prevented by both SIRT2 siRNA and SIRT2 inhibitor, AGK2. SIRT2 siRNA also blocked the NADH-induced increases in glutamate cysteine ligase (GCL) and glutathione. Moreover, SIRT2 siRNA and AGK2 blocked NADH-induced Akt phosphorylation, and inhibition of Akt phosphorylation prevented NADH-induced increases in the nuclear Nrf2 and glutathione. Collectively, our study shows that SIRT2 regulates nuclear Nrf2 levels by modulating Akt phosphorylation, thus modulating the levels of GCL and total glutathione. PMID- 27264720 TI - Origins of sp(3)C peaks in C1s X-ray Photoelectron Spectra of Carbon Materials. AB - X-ray photoelectron spectroscopy (XPS) is among the most powerful techniques to analyze defective structures of carbon materials such as graphene and activated carbon. However, reported assignments of defects, especially sp(3)C and sp(2)C, are questionable. Most reports assign sp(3)C peaks to be higher than sp(2)C peaks, whereas a few reports assign sp(3)C peaks to be lower than sp(2)C peaks. Our group previously reported that calculated binding energies of sp(3)C were basically lower than those of sp(2)C. This work clarified that one of the reasons for the prevailing ambiguous assignments of sp(3)C peaks is charging effects of diamond. PMID- 27264721 TI - Increased peptide YY blood concentrations, not decreased acyl-ghrelin, are associated with reduced hunger and food intake in healthy older women: Preliminary evidence. AB - With ageing there is frequently a loss of appetite, termed anorexia of ageing, which can result in under-nutrition. We do not know how appetite control alters with ageing. The objective of this study was to investigate whether differences in the release of, and response to, gastrointestinal appetite hormones is altered in young compared to old healthy volunteers. We hypothesised that an increase in PYY and GLP-1 or a decrease ghrelin may result in a decreased appetite. A comparative experimental design, using a cross-sectional sample of ages from a healthy population, matched for sex and BMI was used. The study compared total ghrelin, acyl-ghrelin, PYY, GLP-1 and subjective appetite responses to ingestion of a standardised 2781kj (660 kcal) test meal. 31 female volunteers aged between 21 and 92yrs took part. Multiple linear regression showed that both age and sex had an independent effect on energy intake. Subjective appetite scores showed that hunger, pleasantness to eat, and prospective food intake were significantly lower in the older age groups. PYY incremental area under the curve (IAUC) was greater in the oldest old compared to younger ages f(3,27) = 2.9, p = 0.05. No differences in GLP-1, ghrelin or acyl-ghrelin were observed in the older compared to younger age groups. Our data suggest that there may be increases in postprandial PYY(3-36) levels in female octogenarians, potentially resulting in reduced appetite. There does not appear to be any change in ghrelin or acyl ghrelin concentrations with ageing. PMID- 27264723 TI - Hydroxyapatite substituted by transition metals: experiment and theory. AB - Bioceramics are versatile materials for hard tissue engineering. Hydroxyapatite (HA) is a widely studied biomaterial for bone grafting and tissue engineering applications. The crystal structure of HA allows for a wide range of substitutions, which allows for tailoring materials properties. Transition metals and lanthanides are of interest since substitution in HA can result in magnetic properties. In this study, experimental results were compared to theoretical calculations of HA substituted with a transition metal. Calculation of a 10 atomic percent substitution of a transition metal ion Mn(2+), Fe(2+), and Co(2+) substituted HA samples lead to magnetic moments of 5, 4, and 3 Bohr magnetons, respectively. Hydroxyapatite substituted by transition metals (MHA) was fabricated through an ion exchange procedure and characterized with X-ray diffraction, Fourier transform infra-red spectroscopy (FTIR), X-ray photoelectron spectroscopy, and vibrating sample magnetometer, and results were compared to theoretical calculations. All the substitutions resulted in phase-pure M(2+)HA with lattice parameters and FTIR spectra in good agreement with calculations. Magnetic measurements revealed that the substitution of Mn(2+) has the greatest effect on the magnetic properties of HA followed by the substitution of Fe(2+) and then Co(2+). The present work underlines the power of synergistic theoretical experimental work in guiding the rational design of materials. PMID- 27264722 TI - Both de novo synthetized and exogenous fatty acids support the growth of hepatocellular carcinoma cells. AB - BACKGROUND & AIMS: Although it is well established that fatty acids (FA) are indispensable for the proliferation and survival of cancer cells in hepatocellular carcinoma (HCC), inhibition of Fatty Acid Synthase (FASN) cannot completely repress HCC cell growth in culture. Thus, we hypothesized that uptake of exogenous FA by cancer cells might play an important role in the development and progression of HCC. Lipoprotein lipase (LPL) is the enzyme that catalyses the hydrolysis of triglycerides into free fatty acids (FFA) and increases the cellular uptake of FA. METHODS: We used immunohistochemistry and quantitative reverse transcription real-time polymerase chain reaction to evaluate LPL expression in human and mouse HCC samples. Using lipoprotein-deficient medium as well as siRNAs against LPL and/or FASN, we investigated whether human HCC cells depend on both endogenous and exogenous fatty acids for survival in vitro. RESULTS: We found that LPL is upregulated in mouse and human HCC samples. High expression of LPL in human HCC samples is associated with poor prognosis. In HCC cell lines, silencing of FASN or LPL or culturing the cells in lipoprotein deficient medium significantly decreased cell proliferation. Importantly, when FASN suppression was coupled to concomitant LPL depletion, the growth restraint of cell lines was further augmented. CONCLUSIONS: The present study strongly suggests that both de novo synthetized and exogenous FA play a major role along hepatocarcinogenesis. Thus, combined suppression of LPL and FASN might be highly beneficial for the treatment of human HCC. PMID- 27264724 TI - Elevated serum cathepsin B concentration in pregnant women is associated with preeclampsia. AB - PURPOSE: To compare the circulating levels of cathepsins B and D in preeclamptic and normotensive pregnancies. METHODS: Seventy-two pregnant patients were enrolled in this study. Of the 72 pregnant patients, 25 were preeclamptic and 47 patients were normotensive. Serum levels of soluble cathepsins B and D were measured with an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Cathepsin B levels were significantly higher in preeclamptic women than normotensive pregnant women (125.9 vs. 41.9 ng/mL; p = 0.013). The serum levels of cathepsin D were lower in preeclamptic women, but the differences were not significant (129.3 vs. 200.9 ng/mL; p = 0.077). However, cathepsin B and D levels were not correlated with severity of preeclampsia and small for gestational age. The serum levels of cathepsin D were inversely correlated with uric acid in preeclamptic patients (r = -0.527; p = 0.03). CONCLUSION: The serum levels of cathepsin B levels were increased significantly in preeclamptic women. Correlation with severity of preeclampsia needs further investigation to clarify the role of cathepsin B. PMID- 27264725 TI - Controlled Release Oral Delivery of Apigenin Containing Pellets with Antioxidant Activity. AB - BACKGROUND: Drug delivery of phytochemicals has gained interest recently due to their remarkable health effects. Apigenin, a plant flavonoid, has antioxidant, anti-inflammatory and anticancer activities but its delivery is challenging. It could be absorbed through the whole intestine, however, it has poor bioavailability due to its low aqueous solubility. In Europe, the daily intake was estimated to be as low as 3 +/- 1 mg. Pellets offer several advantages such as improved bioavailability and various resultant drug release profiles can be obtained by simply mixing pellets with different coatings. OBJECTIVE: The objective of our study was to develop a carrier system containing 20 mg apigenin thus enhancing intake and to offer reduction of oxidative stress which can cause inflammation in the intestine. METHOD: The apigenin powder was dispersed in aqueous solution of binding material and layered onto the inert cores in a fluidized bed apparatus. The layered cores were further coated with enteric polymers and the process parameters were optimized. RESULTS: The prepared pellets met with the requirements and have good physical characteristic. 10% (w/w) Eudragit(r) L was suitable for enteric coating with a complete release at pH 6.8 within 1 hour. 15% (w/w) Eudragit(r) FS coating ensured acid resistance ability and colonic delivery. The therapeutic efficiency was confirmed with antioxidant activity measurement by using DPPH* assay. CONCLUSION: Enteric coated spheres allow targeted delivery into the intestine and colon thus reaching the main absorption site. Pellets were proved to be an optimal delivery system for apigenin thus providing enhanced apigenin intake. PMID- 27264726 TI - Chemical Engineering in the "BIO" World. AB - Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update. PMID- 27264728 TI - New insights into the hepatitis E virus genotype 3 phylodynamics and evolutionary history. AB - Hepatitis E virus (HEV) is an emergent hepatotropic virus endemic mainly in Asia and other developing areas. However, in the last decade it has been increasingly reported in high-income countries. Human infecting HEV strains are currently classified into four genotypes (1-4). Genotype 3 (HEV-3) is the prevalent virus genotype and the mostly associated with autochthonous and sporadic cases of HEV in developed areas. The evolutionary history of HEV worldwide remains largely unknown. In this study we reconstructed the spatiotemporal and population dynamics of HEV-3 at global scale, but with particular emphasis in South America, where case reports have increased dramatically in the last years. To achieve this, we applied a Bayesian coalescent-based approach to a comprehensive data set comprising 97 GenBank HEV-3 sequences for which the location and sampling date was documented. Our phylogenetic analyses suggest that the worldwide genetic diversity of HEV-3 can be grouped into two main Clades (I and II) with a Tmrca dated in approximately 320years ago (95% HPD: 420-236years) and that a unique independent introduction of HEV-3 seems to have occurred in Uruguay, where most of the human HEV cases in South America have been described. The phylodynamic inference indicates that the population size of this virus suffered substantial temporal variations after the second half of the 20th century. In this sense and conversely to what is postulated to date, we suggest that the worldwide effective population size of HEV-3 is not decreasing and that frequently sources of error in its estimates stem from assumptions that the analyzed sequences are derived from a single panmictic population. Novel insights on the global population dynamics of HEV are given. Additionally, this work constitutes an attempt to further describe in a Bayesian coalescent framework, the phylodynamics and evolutionary history of HEV-3 in the South American region. PMID- 27264727 TI - Common occurrence of Cryptosporidium hominis in horses and donkeys. AB - Extensive genetic variation is observed within the genus Cryptosporidium and the distribution of Cryptosporidium species/genotypes in humans and animals appears to vary by geography and host species. To better understand the genetic diversity of Cryptosporidium spp. in horses and donkeys, we characterized five horse derived and 82 donkey-derived Cryptosporidium isolates from five provinces or autonomous regions (Sichuan, Gansu, Henan, Inner Mongolia and Shandong) in China at the species/genotype and subtype levels. Three Cryptosporidium species/genotypes were identified based on the analysis of the SSU rRNA gene, including Cryptosporidium parvum (n=22), the Cryptosporidium horse genotype (n=4), and Cryptosporidium hominis (n=61). The identification of C. hominis was confirmed by sequence analysis of the HSP70 and actin genes. Subtyping using sequence analysis of the 60kDa glycoprotein gene identified 21 C. parvum isolates as subtype IIdA19G1, the four horse genotype isolates as subtypes VIaA15G4 (n=2) and VIaA11G3 (n=2), and the 61 C. hominis isolates as IkA16G1 (n=59) and IkA16 (n=2). The common finding of C. hominis reaffirms the heterogeneity of Cryptosporidium spp. in horses and donkeys and is possibly a reflection of endemic transmission of C. hominis in these animals. Data of the study suggest that horses and donkeys as companion animals may potentially transmit Cryptosporidium infections to humans. PMID- 27264729 TI - High glucose levels affect spermatogenesis: an in vitro approach. AB - Besides known factors that may cause male infertility, systemic diseases such as diabetes mellitus may further exacerbate a decline in male fertility. This metabolic disease, clinically characterised by a hyperglycaemic phenotype, has devastating consequences in terms of human health, with reproductive dysfunction being one of the associated clinical complications. Nonetheless, the mechanisms responsible for such alterations are still poorly understood due to the multiplicity of factors involved in the induced pathophysiological changes. With this in mind, we focused on the main mediator of diabetes-associated alterations and performed an in vitro approach to address the effects of high glucose conditions on spermatogenesis, avoiding other confounding in vivo factors. Mouse (5 days post partum) testis fragments were cultured on agar gel stands at a gas liquid interface with either 5, 25 or 50mM D-glucose for 3 weeks. Stereological analysis revealed that high D-glucose levels increased Sertoli cell number (P<0.05) and decreased tubular luminal area (P<0.01), suggesting an impairment of this somatic cell type. Moreover, higher proliferative activity in a TM4 Sertoli cell line exposed to high D-glucose was found (P<0.05) without compromising cell viability (P>0.05), further suggesting altered Sertoli cell maturation. Overall, high D-glucose concentrations may lead to impairment of Sertoli cell function, which, given their significant role in spermatogenic control, may compromise male fertility. PMID- 27264730 TI - Unrecognized diversity in New Guinean crayfish species (Decapoda, Parastacidae): The evidence from molecular data. AB - The phylogenetic relationships among imported ornamental crayfish belonging to the genus Cherax were inferred from a combined dataset of 3 mitochondrial genes (COI, 16S and 12S) and by comparison with available GenBank sequences of 14 Cherax species. Furthermore, the concordance of previously described species obtained from a wholesaler (Cherax boesemani, C. holthuisi and C. peknyi) with available GenBank sequences was verified based on COI with special respect to comparison with sequences assigned as Cherax species. Recently described species C. gherardiae, C. pulcher and C. subterigneus belong to the northern group of Cherax species. Comparison and analysis with other GenBank COI sequences show previously unreported diversity of New Guinean species, suggesting 5 putative new species. Surprisingly, species assigned to the subgenus Astaconephrops do not form a monophyletic clade; this subgenus should be reappraised relative to the purported typical morphological characteristic of the uncalcified patch on male chelae. Increasing importation of crayfish underscores the importance of accurate species identification. Use of basic molecular methods is a necessary requisite for documenting occurrence, abundance and population trends of target species. Consequently, it helps to support eventual conservation decision-making by stakeholders. PMID- 27264731 TI - Chronic Effects of Blast-Related TBI on Subcortical Functional Connectivity in Veterans. AB - OBJECTIVES: Blast explosions are the most frequent mechanism of traumatic brain injury (TBI) in recent wars, but little is known about their long-term effects. METHODS: Functional connectivity (FC) was measured in 17 veterans an average of 5.46 years after their most serious blast related TBI, and in 15 demographically similar veterans without TBI or blast exposure. Subcortical FC was measured in bilateral caudate, putamen, and globus pallidus. The default mode and fronto parietal networks were also investigated. RESULTS: In subcortical regions, between-groups t tests revealed altered FC from the right putamen and right globus pallidus. However, following analysis of covariance (ANCOVA) with age, depression (Center for Epidemiologic Studies Depression Scale), and posttraumatic stress disorder symptom (PTSD Checklist - Civilian version) measures, significant findings remained only for the right globus pallidus with anticorrelation in bilateral temporal occipital fusiform cortex, occipital fusiform gyrus, lingual gyrus, and cerebellum, as well as the right occipital pole. No group differences were found for the default mode network. Although reduced FC was found in the fronto-parietal network in the TBI group, between-group differences were nonsignificant after the ANCOVA. CONCLUSIONS: FC of the globus pallidus is altered years after exposure to blast related TBI. Future studies are necessary to explore the trajectory of changes in FC in subcortical regions after blast TBI, the effects of isolated versus repetitive blast-related TBI, and the relation to long-term outcomes in veterans. (JINS, 2016, 22, 631-642). PMID- 27264732 TI - Primary clear cell sarcoma of the head and neck: a case series with review of the literature. AB - BACKGROUND: Clear cell sarcoma typically arises in deep soft tissues of the foot/ankle. Primary head and neck clear cell sarcoma is rare. We report three molecularly confirmed primary head and neck clear cell sarcoma and review the literature. METHODS: Head and neck clear cell sarcoma with no primary elsewhere were retrieved from archival/consultation files. English language literature review of all reported head and neck clear cell sarcoma was performed. RESULTS: Three cases were identified. The tumors, all in men, presented on the scalp of a 33-year-old, face of a 20-year-old and tongue of a 44-year-old. Tumors ranged from 0.6 to 1.4 cm. All had typical features of clear cell sarcoma, including nests of tumor cells divided by fibrous septae. One had multinucleated wreath like giant cells. One had a focal junctional component. Immunohistochemistry was positive for S100 (three out of three), HMB45 (three out of three) and Melan-A (two out of three). All had EWSR1 rearrangements by fluorescence in situ hybridization. Follow up available for one patient revealed no evidence of disease after wide excision and radiation. Seven additional reported cases were identified and tabulated. CONCLUSION: Head and neck clear cell sarcoma is rare but should be considered in the differential diagnosis of nested tumors with fibrous septae. Molecular analysis should be considered for definitive diagnosis regardless of location. PMID- 27264733 TI - Erratum: The somatic mutation profiles of 2,433 breast cancers refine their genomic and transcriptomic landscapes. PMID- 27264734 TI - Identification of differentially expressed genes from multipotent epithelia at the onset of an asexual development. AB - Organisms that have evolved alternative modes of reproduction, complementary to the sexual mode, are found across metazoans. The chordate Botryllus schlosseri is an emerging model for asexual development studies. Botryllus can rebuild its entire body from a portion of adult epithelia in a continuous and stereotyped process called blastogenesis. Anatomy and ontogenies of blastogenesis are well described, however molecular signatures triggering this developmental process are entirely unknown. We isolated tissues at the site of blastogenesis onset and from the same epithelia where this process is never triggered. We linearly amplified an ultra-low amount of mRNA (<10ng) and generated three transcriptome datasets. To provide a conservative landscape of transcripts differentially expressed between blastogenic vs. non-blastogenic epithelia we compared three different mapping and analysis strategies with a de novo assembled transcriptome and partially assembled genome as references, additionally a self-mapping strategy on the dataset. A subset of differentially expressed genes were analyzed and validated by in situ hybridization. The comparison of different analyses allowed us to isolate stringent sets of target genes, including transcripts with potential involvement in the onset of a non-embryonic developmental pathway. The results provide a good entry point to approach regenerative event in a basal chordate. PMID- 27264735 TI - Direct and indirect vitamin A supplementation strategies result in different plasma and tissue retinol kinetics in neonatal rats. AB - Many questions remain regarding vitamin A (VA) supplementation of infants. Herein we compared direct oral VA supplementation of the neonate and indirect treatment through maternal dietary VA (M-VA) treatment on VA status and kinetics in neonatal rats. Treatments included direct VA combined with retinoic acid (RA) [D VARA; VA (6 mg/kg) + 10% RA, given orally to neonates on postnatal day (P)2 and P3] and indirect VA supplementation through increased M-VA, compared with each other and oil-treated neonates. [(3)H]retinol was administered orally to all neonates on P4. Plasma and tissue [(3)H]retinol kinetics were determined from 1 h to 14 days post-dosing. D-VARA versus placebo dramatically increased liver and lung retinol, but only in the first 8-10 days. In M-VA neonates, liver and lung VA increased progressively throughout the study. Compartmental modeling of plasma [(3)H]retinol showed that both D-VARA and indirect M-VA reduced retinol recycling between plasma and tissues. Compartmental models of individual tissues predicted that D-VARA stimulated the uptake of VA in chylomicrons to extrahepatic tissues, especially intestine, while the uptake was not observed in M-VA neonates. In conclusion, indirect maternal supplementation had a greater sustained effect than D-VARA on neonatal VA status, while also differentially affecting plasma and tissue retinol kinetics. PMID- 27264736 TI - Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha. AB - Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2-4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2-4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2-4) by fusing the variable region of mouse mAb 2-4 to the constant region of feline antibody. The chimeric mAb 2-4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2-4 and chimeric mAb 2-4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2-4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2-4 was reduced. In contrast, in cats treated with chimeric mAb 2-4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2-4-treated cats. PMID- 27264737 TI - Subcutaneous rhabdomyosarcoma in an old rabbit. AB - An 11-year-old castrated male rabbit presented with a subcutaneous mass in the right hind limb. The mass comprised solid and myxoid areas. Solid areas were characterized by a storiform or interlacing pattern of spindle cells, strap cells, multinucleated giant cells and round cells with eccentrically located nuclei, whereas the myxoid areas were composed predominantly of elongated fusiform cells with hyperchromatic nuclei embedded in Alcian Blue-positive myxoid stroma. Immunohistochemically, tumor cells in both areas were positive for desmin and vimentin. Ultrastructurally, the tumor cells in the solid areas had abundant myofilaments with electron dense Z-band structures. Based on these pathological findings, this case was diagnosed as rhabdomyosarcoma in a rabbit. PMID- 27264738 TI - Does bovine besnoitiosis affect the sexual function of chronically infected bulls? AB - Bovine besnoitiosis is a reemerging disease in Europe. The clinically Besnoitia besnoiti infection in bulls is characterized by fever, nasal discharge, and orchitis in the acute phase and by scleroderma in the chronic phase. However, in many bulls, B besnoiti infection remains at a subclinical stage. Bull infertility is an economically relevant consequence of besnoitiosis infection. It is not clear, however, if semen quality returns to normal levels when infected animals have clinically recovered. The aim of this study was to examine the relationship between chronic besnoitiosis and bull sexual function in a region of eastern France, where the disease is reemerging, by comparing semen quality and genital lesions in 11 uninfected, 17 subclinically infected, and 12 clinically infected bulls. The presence of anti-B besnoiti antibodies was detected by Western blot test. Semen was collected by electroejaculation. Bulls clinically infected with B besnoiti showed significantly more genital tract alterations than uninfected or subclinically infected bulls. No relationship was evidenced between besnoitiosis infectious status and semen quality, whereas a significant relationship was noted between genital lesions and semen score. This means that in the absence of moderate to severe genital lesions, chronic bovine besnoitiosis is unlikely to alter semen quality. However, as the presence of infected animals could lead to spread of the disease, culling or separation of clinically infected bulls from the remaining healthy animals is strongly recommended. PMID- 27264739 TI - Identification of vessel degeneration and endometrosis in the equine endometrium, using narrow-band imaging hysteroscopy. AB - In this study, endometrosis and angiosclerosis in mares were studied. Endometrosis is a severe, progressive, and irreversible fibrotic condition that affects the endometrium, whereas angiosclerosis refers to thickening of vessel walls due to degenerative changes leading to reduced elasticity of the walls and lower perfusion. Histologic evaluations were performed on biopsies and compared with vascular features of the endometrial surface obtained via narrow-band imaging (NBI) hysteroscopy. First, it was determined if hysteroscopic evaluation of the endometrium using NBI resulted in a better visualization of the vascular pattern (i.e., vessel-versus-background contrast was increased) compared with using white light. This was found to be the case for examinations in vivo (n = 10), but not when using abattoir uteri (n = 3). In the second part of this study, it was determined if vascular densities and sizes as derived from NBI images could be used as indicators for the degree of degenerative changes of the equine endometrium and its vessels. Narrow-band imaging hysteroscopic evaluations were performed (n = 10), and endometrial biopsies (n = 32) were collected. Histologic specimens were evaluated for degree of endometrosis and angiosclerosis, and they were classified in Kenney categories. Narrow-band imaging images were analyzed for vascular pattern. Samples classified to Kenney category I, or without signs of vessel degeneration, had significantly higher vascular densities than samples from Kenney category IIa or with angiosclerosis. In conclusion, narrow-band imaging facilitates enhanced visualization of the vasculature of the equine endometrium during hysteroscopies, which has applications in detection of endometrosis and angiosclerosis. PMID- 27264740 TI - Lentiviral transgenesis in mice via a simple method of viral concentration. AB - Transgenic animals are important in vivo models for biological research. However, low transgenic rates are commonly reported in the literature. Lentiviral transgenesis is a promising method that has greater efficiency with regard to generating transgenic animals, although the transgenic rate of this approach is highly dependent on different transgenes and concentrated lentiviruses. In this study, we modified a method to concentrate lentiviruses using a table centrifuge, commonly available in most laboratories, and carried out analysis of the transgenic efficiency in mice. Based on 26 individual constructs and 627 live pups, we found that the overall transgenic rate was more than 30%, which is higher than obtained with pronuclear microinjection. In addition, we did not find any significant differences in transgenic efficiency when the size of inserts was less than 5000 bp. These results not only show that our modified method can successfully generate transgenic mice but also suggest that this approach could be generally applied to different constructs when the size of inserts is less than 5000 bp. It is anticipated that the results of this study can help encourage the wider laboratory use of lentiviral transgenesis in mice. PMID- 27264741 TI - Blastocyst recovery and multifactorial gene expression analysis in the wild guinea pig (Cavia aperea). AB - The expression of specific developmentally important genes in preimplantation embryos is an accepted marker for unraveling the influence of single factors in studies that are mostly related to artificial reproduction techniques. Such studies, however, often reveal high levels of heterogeneity between single embryos, independently of the influence of factors of interest. A possible explanation for this variation could be the large variety of physiological and environmental factors to which early embryos are exposed and their ability to react to them. Here, we investigated several potentially important parameters of development at the same time, in blastocysts of the wild guinea pig (Cavia aperea) generated in vivo after natural mating. The optimal time for flushing fully developed blastocysts was between 123 and 126 hours after mating. The abundance of POU5F1 (P = 0.042), BAX (P < 0.001), SLC2A1 (P = 0.017), and DNMT3A (P < 0.001) mRNA changed significantly over time after mating. The number of sibling embryos present influenced STAT3 levels significantly (P = 0.02). Levels of BAX and POU5F1 were significantly affected by season (P = 0.03 and 0.04). The temporal pattern of SLC2A1 levels was significantly altered both after feeding a protein-deficient diet (P = 0.04) and temperature treatment (P = 0.04) of the sire. In addition, the identity of the father had a significant influence on POU5F1 (P = 0.049) and STAT3 (P < 0.001) mRNA abundances. These data report that the expression of specific genes in early embryos reflects the entire heterogeneity of their surroundings and that it is a plastic reaction toward a multifactorial environment. PMID- 27264742 TI - Facile "one-pot" synthesis of poly(methacrylic acid)-based hybrid monolith via thiol-ene click reaction for hydrophilic interaction chromatography. AB - A novel sol-gel "one-pot" approach in tandem with a radical-mediated thiol-ene reaction for the synthesis of a methacrylic acid-based hybrid monolith was developed. The polymerization monomers, tetramethoxysilane (TMOS) and 3 mercaptopropyl trimethoxysilane (MPTS), were hydrolyzed in high-concentration methacrylic acid solution that also served as a hydrophilic functional monomer. The resulting solution was then mixed with initiator (2, 2'-azobis (2 methylpropionamide) dihydrochloride) and porogen (urea, polyethylene glycol 20,000) in a capillary column and polymerized in water bath. The column had a uniform porous structure and a good permeability. The evaluation of the monolith was performed by separation of small molecules including nucleosides, phenols, amides, bases and Triton X-100. The calibration curves for uridine, inosine, adenosine and cytidine were determined. All the calibration curves exhibited good linear regressions (R(2)>=0.995) within the test ranges of 0.5-40MUg/mL for four nucleosides. Additionaliy, atypical hydrophilic mechanism was proved by elution order from low to high according to polarity retention time increased with increases in the content of the organic solvent in the mobile phase. Further studies indicated that hydrogen bond and electrostatic interactions existed between the polar analytes and the stationary phase. This was the mechanism of retention. The excellent separation of the BSA digest showed good hydrophility of the column and indicated the potential in separation of complex biological samples. PMID- 27264743 TI - Features of a truxene-based stationary phase in capillary gas chromatography for separation of some challenging isomers. AB - Herein we report the first example of exploring truxene-based derivatives for gas chromatographic (GC) separations. The fabricated thiophene-functionalized truxene (TFT) column exhibited weak polarity and efficiencies as high as 4000plates/m for 0.250mm i.d. columns. TFT column showed preferential retention for halogenated and alkyl benzene analytes, and especially, high resolving capability for the xylene isomers, di- and trichlorobiphenyls (di-CB and tri-CB) isomers. Interestingly, its unique retentions for the latter analytes were found to be closely related with their dihedral angles and the locations of chlorine atoms. This finding on the retention trend has not been reported in GC separations, which may provide a new perspective in elucidating retention behaviours for specific analytes. Moreover, TFT column exhibited high thermal stability up to 320 degrees C and excellent repeatability. This work demonstrates the promising future of truxene derivatives in the separation science. PMID- 27264744 TI - Development of an ion-pair liquid chromatography-high resolution mass spectrometry method for determination of organophosphate pesticide metabolites in large-scale biomonitoring studies. AB - Organophosphate based pesticides are widely used in the agricultural sector, and exposure to these chemicals is common for the general population. Pesticides are toxic due to the inhibition of acetylcholinesterases, and the potential for adverse health effects have been investigated in past and recent studies. Human biomonitoring of organophosphate pesticide exposure is carried out through the determination of the metabolites in urine (dialkylphosphates, DAPs). Hereby we present a new method for determination of the 6 non-specific metabolites dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl thiophosphate (DETP), dimethyl dithiophosphate (DMDTP), and diethyl dithiophosphate (DEDTP) in urine based on off-line solid phase extraction (anion exchange, 96-well plates) followed by ion-pair ultra-performance liquid chromatography time-of-flight mass spectrometry. Recoveries and accuracies in control urine spiked at 5ng/mL ranged from 48% to109% and from 91% to 115%, respectively. The method limits of detection for the DAPs were 1.2ng/mL for DMP, 0.38ng/mL for DEP, 0.20ng/mL for DMTP, 0.33ng/mL for DETP, 0.64ng/mL for DMDTP, and 0.15ng/mL for DEDTP. The method was applied to samples from a Norwegian mother/child study group (n=48/56) and the DAPs detection frequencies in urine from mothers and children were about: 40% for DMP, 95% for DEP, 96% for DMTP, 50% for DETP, 15% for DMDTP, and 1% for DEDTP. In both mothers and children, the most abundant DAPs were DMTP (median 2.4/5.2ng/mL) and DEP (median 2.6/3.4ng/mL) followed by DMP (median 1.5/2.1ng/mL). The SG corrected concentrations of DEP and DETP in mothers were statistically higher than in children (p-value<0.05; Mann Whitney test) which might suggest a higher exposure to pesticides in these mothers, or significant differences in toxicokinetics between adults and children. The method was proven robust and suitable for large-scale biomonitoring studies. PMID- 27264745 TI - Quantification of active infliximab in human serum with liquid chromatography tandem mass spectrometry using a tumor necrosis factor alpha -based pre analytical sample purification and a stable isotopic labeled infliximab bio similar as internal standard: A target-based, sensitive and cost-effective method. AB - The therapeutic monoclonal antibody Infliximab (IFX) is a widely used drug for the treatment of several inflammatory autoimmune diseases. However, approximately 10% of patients develop anti-infliximab antibodies (ATIs) rendering the treatment ineffective. Early detection of underexposure to unbound IFX would result in a timely switch of therapy which could aid in the treatment of this disease. Streptavidin coated 96 well plates were used to capture biotinylated-tumor necrosis factor -alpha (b-TNF-alpha), which in turn was used to selectively extract the active form of IFX in human serum. After elution, IFX was digested using trypsin and one signature peptide was selected for subsequent analysis on liquid chromatography-tandem mass spectrometry (LC-MS/MS). The internal standard used was a stable isotopic labeled IFX bio-similar. The assay was successfully validated according to European Medicines Agency (EMA) guidelines and was found to be linear in a range of 0.5-20MUg/mL (r(2)=0.994). Lower limit of quantification for the assay (<20% CV) was 0.5MUg/mL, requiring only 2MUL of sample. Cross-validation against enzyme-linked immunosorbent assay (ELISA) resulted in a high correlation between methods (r(2)=0.95 with a rhoc=0.83) and the accuracy was in line with previously published results. In conclusion, a sensitive, robust and cost-effective method was developed for the bio-analysis of IFX with LC-MS/MS by means of a target-based pre-analytical sample purification. Moreover, low volume and costs of consumables per sample promote its feasibility in (pre)clinical studies and in therapeutic drug monitoring. This method should be considered as first choice due to its accuracy and multiple degree of selectivity. PMID- 27264748 TI - Hematopoietic Stem Cells Transplantationin Neurodegenerative Diseases. PMID- 27264746 TI - Supersonic Dislocation Bursts in Silicon. AB - Dislocations are the primary agents of permanent deformation in crystalline solids. Since the theoretical prediction of supersonic dislocations over half a century ago, there is a dearth of experimental evidence supporting their existence. Here we use non-equilibrium molecular dynamics simulations of shocked silicon to reveal transient supersonic partial dislocation motion at approximately 15 km/s, faster than any previous in-silico observation. Homogeneous dislocation nucleation occurs near the shock front and supersonic dislocation motion lasts just fractions of picoseconds before the dislocations catch the shock front and decelerate back to the elastic wave speed. Applying a modified analytical equation for dislocation evolution we successfully predict a dislocation density of 1.5 * 10(12) cm(-2) within the shocked volume, in agreement with the present simulations and realistic in regards to prior and on going recovery experiments in silicon. PMID- 27264747 TI - Hot topics in lupus nephropathy: Responses from a new 2015 Spanish guideline. PMID- 27264750 TI - Cell-Cell Interactions in Thrombosis: Modulation of Platelet Function and Possibilities of Pharmacological Control with Aspirin. PMID- 27264749 TI - Natural Coagulation Inhibitors and Inflammation. PMID- 27264751 TI - The Role of Antithrombin Agents and Factor Xa-Inhibitors in Antithrombotic Treatment. AB - Hirudin, the first specific thrombin inhibitor, which was used clinically, stems from medicinal leeches and is produced today by recombinant technology. R hirudins have been studied in many clinical trials. R-hirudin has been shown to be more effective than low molecular weight heparin in the prevention of deep venous thrombosis after total hip replacement. In acute coronary syndromes hirudin and the chimeric oligoaminoacid peptide bivalirudin have also been effective. In acute coronary syndromes and when administered together with aspirin high doses of hirudin were associated with an increased risk of bleeding. Hirudin and argatroban successfully prevented thrombotic episodes in patients with heparin-induced thrombocytopenia type II. Several new orally active specific thrombin inhibitors are in development. The combined use of subcutaneous and oral administration of ximelagatran in patients with hip or knee replacement has led to promising results. It seems likely that in the future oral thrombin inhibitors may replace vitamin K-antagonists in some indications. The pentasaccharide fondaparinux is an indirect inhibitor of F Xa. Its anticoagulant and antithrombotic effect depends on the activation of antithrombin. Fondaparinux has shown remarkable antithrombotic efficacy in patients with high risk orthopedic surgery and has been approved in the US and in Europe. Several new low molecular weight specific F Xa-inhibitors are in different stages of development for i.v. and oral use. PMID- 27264752 TI - Role of Iron Chelation Therapy in Thalassemia Major. PMID- 27264754 TI - Vascular Haematology: The Growing Discipline at the Interface of Cardiology and Haematology. PMID- 27264753 TI - Immunobiology and Pathophysiology of Heparin-Induced Thrombocytopenia/ Thrombosis Syndrome-An Update. AB - Heparin-induced thrombocytopenia (HIT) syndrome is one of the more frequent and dangerous autoimmune complications of heparin therapy in clinical setting. It is now widely accepted that heparins are capable of complexing with endogenous chemokines and modify at molecular level to trigger the HIT-associated antibodies responsible for pathogenesis. Newer evidence suggests a functional heterogeneity in the HIT antibodies. Besides platelet factor IV (PF IV), there are several endogenous factors, which are responsible for the upregulation of HIT antibodies in various prophylactic and therapeutic regimens. While the pathophysiology and the mechanisms of action in HIT are rather complex, the role of IgG subtype antibodies is clearly established in mediating the pathogenesis. Currently available antithrombin drugs seem to be promising therapeutic modalities to combat the severe thrombotic episode and platelet activation associated with HIT. The clinical relevance of the pathologically nonfunctional HIT antibodies and the mechanism(s) of their formation, in terms of both correlative evidence and causal relationships, need further investigation. PMID- 27264755 TI - Development of a Synthetic Heparin Pentasaccharide: Fondaparinux. AB - Fondaparinux (Arixtra(r); Sanofi-Synthelabo/Organon) is the first of a new class of antithrombotic agents distinct from low molecular weight (LMW) heparins and heparin. It is a synthetic pentasaccharide mimicking the site of heparin that binds to antithrombin III (AT). It is homogeneous with a molecular weight of 1728 Da. It exhibits only factor (F) Xa inhibitor activity via binding to AT, which in turn inhibits thrombin generation. It does not inhibit thrombin, release TFPI, or possess other actions of heparin. Low AT levels can limit the efficacy of fondaparinux. There is nearly complete bioavailability subcutaneously, rapid onset of action, a prolonged half-life (15- 20 h) and no metabolism preceding renal excretion. Elderly and renal impaired patients have reduced clearance. The PT, aPTT and ACT are not affected by fondaparinux; anti-FXa assays are used if needed. Phase IIb clinical studies have identified a fixed dose of 2.5 mg once daily for prophylaxis of venous thrombosis without monitoring. Four phase III studies (n > 7000) demonstrated a combined 55% relative risk reduction of venous thromboembolic events in orthopedic surgery patients in comparison to the LMW heparin enoxaparin. Hemorrhagic complications for fondaparinux were either comparable to or higher than that for LMW heparin. The US FDA and the European CPMP have approved fondaparinux for prophylaxis of venous thrombosis after orthopedic surgery with limitations of use in elderly, low weight, renal impaired patients and in those receiving spinal anesthesia. Marketing is expected in Spring 2002. Clinical trials for treatment of established thrombosis, coronary syndromes and adjunct to thrombolytic therapy are in progress. PMID- 27264757 TI - Anticoagulation (ECAA): Studies on Computer-Assisted Anticoagulant Dosage. PMID- 27264756 TI - The Role of Thrombolytic Drugs in the Management of Acute Myocardial Infarction and Stroke. PMID- 27264758 TI - Looking Backwards to the Future: The WHO Haemoglobin Colour Scale. AB - The Haemoglobin Colour Scale was developed for WHO as a simple, cheap, pocket sized device for providing a reading of haemoglobin within 1 g/dL of true value. It is intended for the clinician/health worker without easy access to a laboratory, and it thus has an important role in management of anaemia in peripheral health services, especially in under-resourced areas, as well as in antenatal and child health programmes, in screening blood donors and for point-of care anaemia checks anywhere. An international validation trial and other studies have confirmed its reliabilty when tested against reference haemoglobinometry. It is much more reliable than clinical examination in assessing the severity of anaemia and it has advantages over copper sulphate in blood donor screening. PMID- 27264759 TI - Haemophilia in Greece. A Continuous Struggle for Survival and Quality of Life. PMID- 27264761 TI - Insulin Resistance Syndrome: Main Villain of Current and Rising Coronary Risk Among Turks. PMID- 27264760 TI - Acquired Hemophilia in Pediatric Population. AB - The development of acquired inhibitors against the factor VIII protein in childhood period, is a very rare disorder in nonhemophiliac persons but may be clinically important condition due to potential serious bleedings. We have investigated acquired hemophilia development frequency in children with potential high risk groups. Totally 483 nonhemophiliac children including healthy controls were enrolled the study. Age range was 2 to 20 years and mean age was 11 +/- 5.4 years. Risk groups for acquired hemophilia were selected among sick children with transfusion dependent beta- thalassemia major (n= 75), children with malignancy (n= 55), asthma bronchiale (n= 65), type I insulin dependent diabetes mellitus (n= 63), collagen tissue disorders (n= 35). Age-matched 190 healthy children were selected as for healthy control group. Inhibitor tests were performed by the method of Bethesda assay. We have found only two patients who had acquired factor VIII inhibitor among 483 children. These two patients were solid tumor (osteosarcoma) and type I insulin dependent diabetes mellitus. Other risk groups and healthy controls have not inhibitor positivity. As a conclusion, acquired inhibitors should be considered for the differential diagnosis of unusual bleeding episodes in patients who had risk factors of all age groups including childhood period. PMID- 27264762 TI - Biological Determinants of Fasting and Postload Plasma Homocysteine Levels in Healthy Italian Subjects. AB - Genetic and nutritional factors are determinants of total plasma homocysteine (tHCy) whose increased levels play a pathogenic role in atherothrombosis and cardiovascular disease. This study investigated the influence of sex, age, creatinine, serum folate, vitamin B12 and vitamin B6 (pyridoxal- 5-phosphate, PLP) on fasting (FtHCy) and two hour postmethionine loading levels of tHCy in 147 apparently healthy subjects (M/F= 82/65, age range: 14-94 y). FtHCy was higher in men than women (9.89 vs 8.00 MUmol/L, p< 0.01). In males, the main determinants of FtHCy were age and folate levels, respectively explaining 20.5% and 19.0% of FtHCy variance. In women, besides age (22.6%), vitamin B12 (17.8%) rather than folate was a major determinant of FtHCy. Two hour postload tHCy, expressed both as absolute value (PML) and as the difference between 2 hour postload tHCy and FtHCy (delta tHCy) was negatively correlated with folate in both sexes, and with vitamin B12 and age in women only. In males folate was the main determinant, explaining 20% of the variance of postload values, while in females vitamin B12 and PLP were predominant, explaining respectively 40% and 20% of that variance. Age was not among the main determinants of postload values in either sex. These results demonstrate that age and vitamin status differently influence both the fasting and the postmethionine plasma homocysteine levels in normal subjects. PMID- 27264763 TI - Aspirin Responsive Thrombotic Complications in Thrombocythemia Vera. A Novel Platelet-Mediated Arterial Thrombophilia. AB - Erythromelalgia is the main, pathognomonic and presenting symptom in patients with Essential Thrombocythemia and thrombocythemia associated with Polycythemia Vera. Complete relief of erythromelalgic and acrocyanotic pain is obtained with the cyclooxygenase inhibitors aspirin and indomethacin, but not with sodiumsalicylate, dipyridamol, sulfinpyrozone and ticlopedine indicating that platelet-mediated cyclooxygenase metabolites are necessary for erythromelalgia to develop. Local platelet consumption in erythromelalgic areas became evident by the demonstration of arteriolar fibromuscular intimal proliferation and occlusions by platelet-rich thrombi in skin biopsies, by the findings of shortened platelet survival times, significant higher levels of platelet activation markers beta-thromboglobulin (beta-TG), thrombomoduline and increased urinary thromboxane B2 excretion in thrombocythemia patients suffering from erythromelalgia. Aspirin treatment of erythromelalgia in thrombocythemia patients resulted in disappearance of the erythromelalgic, thrombotic signs and symptoms, correction of the shortened platelet survival times, and significant reduction of the increased levels of beta-TG, PF IV, thrombomodulin and urinary T x B2 excretion to normal. Erythromelalgia is frequently preceded or followed by atypical transient neurologic, ocular or coronary ischemic symptoms, which specifically responds to low-dose aspirin or reduction of platelet counts to normal. The broad spectrum of acropareshesias, erythromelalgia and acrocyanotic ischemia together with the episodic and transient atypical TIAs and ocular or coronary ischemic symptoms all are the consequence of one underlying disorder of aspirin-responsive and platelet-mediated arterial thrombophilia precipitated by spontaneous activation and aggregation of hypersensitive platelets in the endarteial microvasculature involving the peripheral, cerebral and coronary circulation of thrombocythemia patients. PMID- 27264764 TI - Plasma Levels of Plasminogen Activator Inhibitor-1 (PAI-1) and Thrombin Activatable Fibrinolysis Inhibitor (TAFI) in Patients with Disseminated Intravascular Coagulation (DIC). AB - Plasma levels of thrombin activatable fibrinolysis inhibitor (TAFI) and total plasminogen activator inhibitor-1 (PAI-1) and tissue type plasminogen activator (tPA)/PAI-1 complex in patients with disseminated intravascular coagulation (DIC) to examine the relationship between hypofibrinolysis and the pathogenesis with DIC. We examined 39 patients with DIC, 23 with pre-DIC, 181 without DIC and 17 healthy volunteers. Both plasma levels of total PAI-1 and tPA/PAI-1 complex were significantly high in patients with DIC. Those levels were also high in patients with organ failure, especially sepsis. Both TAFI activity and antigen levels in the plasma were significantly low in patients with DIC. TAFI activity in plasma was correlated with TAFI antigen. TAFI activity and antigen levels were negatively correlated with TAT and D-dimer. The TAFI activity in plasma was significantly low in patients with infection and in those with organ failure, suggesting that TAFI may play an important role in the mechanism of organ failure in DIC-associated sepsis. Regulation of fibrinolysis by TAFI and PAI-1 may play an important role in the pathogenesis of DIC and organ failure. PMID- 27264765 TI - Trace Element Analyses (Zinc and Selenium) in Pediatric Malignant Lymphomas. AB - Ninetysix untreated patients with Malignant lymphoma's, 81 Hodgkin's disease and 15 Burkitt's lymphoma were studied for zinc (Zn) and selenium (Se) status. Plasma and hair Zn, and Se levels were measured by atomic absorption spectrophotometry. Chronic Zn and Se deficiencies (low plasma and low hair Zn and Se levels together) were found to be associated with Malignant lymphoma's in Turkish children. This was most likely due to poor "nutritional environment" of the patients since majority of the Malignant lymphoma cases were from low socioeconomic class. Supplemention of the patients with physiological doses of Zn and Se, in addition to standard chemo radiotherapy regimen was proposed. PMID- 27264766 TI - Molecular Approach to Turkish Pediatric Stroke Patients. PMID- 27264767 TI - Looking for Our Ten Years Results for Coronary Heart Disease and Ischemic Stroke Group for the Standpoint of Haemostasis. AB - To evaluate the role the coagulation and fibrinolysis abnormalities in the pathogenesis of ischemic stroke of undetermined etiology, we assayed plasma concentration of fibrinopeptide-A and thrombin-antithrombin III complex, both sensitive markers for thrombin activation and fibrin formation, and D-dimer, a marker of plasmin activity and fibrinolysis. Hemostatic markers were measured in 32 patients with acute stroke and 20 patients with chronic stroke, and compared with 21 normal subjects. Fibrinopeptid-A and thrombin-antithrombin III complex levels were not elevated significantly, whereas the D-dimer level was markedly raised in acute (p<< 0.001) and chronic (p< 0.05) phases of ischemic stroke in comparison with the control group. Prolonged elevation of D-dimer concentration suggests that hemostatic abnormalities have a primary role in the pathogenesis of ischemic stroke. The measurement of D-dimer concentration may help to better decide the indications for therapy of the patients with ischemic stroke of undetermined etiology. PMID- 27264768 TI - Acute Effects of 17beta-Estradiol and ATP on Endothelial Cells; Effects of Genistein and PMA on Calcium Response. AB - Various studies have shown that 17beta-estradiol (E2), has acute effects on cardiovascular system in addition to its genomic effect. Acute administration of E2 had been shown to increase intracellular free calcium concentration (Ca+2)i in human umbilical vein endothelial cells (HUVEC). The present study investigates the signalling pathway responsible for Ca+2 response to E2. In the study, the effect of E2 on phosphoinositide turnover was investigated by use of Dowex-1 anion-exchange columns after labeling cells with myo(3H)inositol. Additionally, the effects of tyrosine phosphorylation inhibitor genistein and protein kinase C activator 4beta-phorbol-12beta-myristate-13-acetate (PMA) on the Ca+2 response to E2 and ATP were investigated and compared in fura-2 loaded HUVEC. The data demonstrates that E2 treatment causes 45% increase in inositol phosphate production in parallel to increases in (Ca+2)i. Genistein and PMA inhibit the Ca+2 response to E2 ~75%, 49%, while they inhibit the response to ATP ~62%, 73% respectively. Our data suggests the involvement of PLC in the signaling stimulated by E2 and indicate the involvement of tyrosine phosphorylation and PKC. Differences in the effect of the inhibitors on E2- and ATPinduced responses suggest that there may be differences in the upstream signaling initiated by E2 and ATP, such as different roles for tyrosine phosphorylation. PMID- 27264769 TI - Platelet Labeling for Determination of Lifespan. AB - After various earlier attempts with different radiotracers 51chromium and finally ^IndiumoKIne became the tracers of choice for the radiolabeling of human platelets and the subsequent monitoring of in vivo kinetics. Data on clinical application of platelet survival in atherosclerotic vascular disease and a variety of risk factors are presented. Furthermore, a new approach to use nonradioactive material (rubidium) as label for platelets allowing application in children and pregnants, where only the information on platelet survival is necessary, are discussed. The application of 111lndium-oxine and cold rubidium is an underused reiiable methodology for the assessment of lifespan of human platelets for clinical diagnosis and treatment monitoring. PMID- 27264770 TI - Thrombosis and Cancer. PMID- 27264771 TI - The Prevalence of Activated Protein C Resistance and F V Leiden in Healthy Population of Edirne, Turkey. AB - Activated protein C (APC) resistance has been found to be an important cause of venous thrombosis. The prevalence of F V Leiden (FVL) in general population is variable according to the region and the ethnic group. The aim of this study was to determine the prevalence of APC resistance and FVL in healthy population in Edirne as a representative sample of province of Edirne. Total 467 healthy subjects were studied. There were 238 males (50.96%) and 229 females (49.04%). APC resistance was studied by functional and DNA methods. There were a total 22/476 subjects (4.7%) were APC resistance. There were 20/476 subjects (4.28%) who had FVL by DNA test. Of these, there were 18 heterozygous and 2 homozygous FVL and other two subjects have no FVL mutation but have the high levels of FVIII to explain acquired APC resistance. The coexistence of FVL and the deficiencies of protein C (1/22), protein S (2/22) and antithrombin (1/22) were also studied. No one of subjects had prothrombin gene mutation. The data showed that the prevalence of APC resitance and FVL in healthy Turkish population were similar to the previously reported publications in Turkey and Europe. One thing is a keeping in mind to be the coexistence of FVL and the other known thrombophilic risk factors. PMID- 27264772 TI - Endocrinologic Late Effects of Chemoradiotherapy in Pediatric Acute Leukemia. AB - This study intends to describe growth and endocrine disorders secondary to chemotherapy among long-term survivors of pediatric acute leukemia. Sixteen patients including 14 ALL and 2 AML entered the study. Four were females and 12 were males with the mean age of 17.38 +/- 3.81 years. Following the completion of their therapy, the mean follow up period of the patients was 62.43 +/- 41.11 months. Somatic growth, sexual maturation, hypothalamic- pituitary-thyroid axis and hypothalamic-pituitary-gonadal axis were evaluated in all the patients. Two out of 16 had pathologic short stature (12.5%) and 3 patients had enuchoid status (18.75%) with antrophometric measurements. Eleven patients had normal thyroid gland dimensions and homogeneous thyroid tissue on ultrasonographic examination. One patient had Ia and another four patients had Ib diffuse goitre according to WHO criteria. Two out of 16 patients were diagnosed as subclinic primary hypothyroidism (12.5%), and three of them were diagnosed as subclinic central hypothyroidism (18.75%) according to TRH testing. Three patients were subclinic subtle central hypothyroidism. Thyroid auto-antibodies were in normal range in all patients. Eight patients (66.6%) out of 12 male subjects revealed impaired HHG axis. Hypergonadotropic hypogonadism (Leydig and Sertoli dysfunction) were observed in five of them and isolated Sertoli dysfunction was detected in three of them. Azoospermia was encountered in all patients with isolated Sertoli dysfunction. Testicular biopsy was obtained from only one of them and atrophic testicular tissue was detected. Female patients show normal pubertal development and gonadal functions. CONCLUSION: Subclinic subtle primary and subclinic central hypothyroidism were found in 31.2%, impaired Sertoli and Leydig with Sertoli cell function in 66.66% of long-term survivors pediatric acute leukemia and testicular tissue was more sensitive to adverse effects of chemotherapy than ovarian tissue. PMID- 27264773 TI - Effect of Donor Age on the Deformability and Aggregability of Density-Separated Red Blood Cells. AB - Deformability of density-separated red blood cells (RBC) was determined in individuals, in three different age groups. The "young" group was composed of eight individuals between 22-30 years of age; there were eight individuals between 35-45 years of age in the "mid-age" group and 8 individuals between 60-85 years of age in the "old" group. Density separation was performed using discontinuous, Iodixanol (Optiprep(r)) density gradients. Five layers of Iodixanol with densities between 1.075 and 1.115 g/mL were used. The density distribution of RBC was estimated by determining the hemoglobin concentration in each layer, after centrifugation. The RBC deformability was measured by ektacytometry in least and most dense RBC fractions. In all age groups, the RBC were mostly accumulated in the layers with 1095 and 1105 g/mL densities. In the "young" group, about 80% of RBC were distributed in each of these gradients almost equally. In the "old" group, 50% of RBC were in 1095 g/mL density layer, while 28% was present in the 1105 g/mL layer. The values for "mid-age" group were in between "young" and "old" groups. In all age groups, EI of denser RBC were smaller, in comparison with the RBC in less dense layers. However, the difference between the EI of less and more dense RBC was more pronounced in the "old" group. RBC aggregation was found to be higher in denser RBC fraction, but the difference was less pronounced in "old" group. These results suggest that, RBC circulating in the vasculature of "aged" individuals exhibit more pronounced rheological alterations, during the aging process of RBC. PMID- 27264774 TI - The Frequency and Distribution Pattern of beta-Thalassemia Mutations in Turkey. AB - beta-thalassemia, a-thalassemia and sickle cell anemia are the three most common hemoglobinopathies in Turkey. beta-thalassemia major makes up 73%, sickle cell anemia 23% and Hb H disease 4% of total patients with hemoglobinopathy. The overall frequency of beta-thalassemia is 2%. However, the frequency shows regional variations and in some areas it is as high as 13%. Molecular studies indicated the presence of more than 35 different mutations associated with beta thalassemia. In this study it was shown that five different mutations, namely IVSI-110 (G-A), IVSI- 6 (T-C), IVSII-1 (G-A), IVSII-745 (C-G) and IVSI-1 (G-A) make up 71% of all beta-thalassemia mutations. The rate of consanguineous marriage in families with thalassemia major is %63. However, in 11% of these families, parents carry two different thalassemia mutations. The IVSI-1 (GAEA) mutation is most prevalent in the Aegean Region and it seemed that this mutation moved from this region toward Marmara, Black Sea, Middle, East and South- eastern Anatolia. The IVSII-745 (C-G) is most prevalent in the Mediterranean region and it moved toward Central Anatolia, Black Sea and South-eastern Anatolia. Contrary to these two mutations FSC8 (-AA), IVSII-1 (GA) and -30 (T-A) mutations are most prevalent in Eastern Anatolia and they moved from this region to South-eastern Anatolia, Mediterranean Region, Central Anatolia and Aegean Region. The frequency of various mutations in Central Anatolia is very close to the mean figures given for Turkey indicating that these mutations are well mixed in this region. Sickle cell anemia and sickle cell beta-thalassemia are almost exclusively seen in eastern coast of Mediterranean Sea and in Thrace. PMID- 27264775 TI - Hematopoetic stem celi transplantation activity at a single center: Cerrahpasa experience. AB - At our institution 94 transplantations have been performed in an 8 year period up to December 2001. Forty-three females and 49 males with ages ranging from 14 to 61 years received 67 allogeneic (allo) and 27 autologous (auto) transplants; 2 patients were transplanted twice. The diagnosis of allo transplants were AML (27 patients-pts), CML (17 pts), ALL (16 pts) and AA (5 pts); those of auto transplants were NHL (13 pts), HD (10 pts), MM (3 pts) and AML (l pt). Of the patients with acute leukemia 69.7% were in first CR and ali but one of the patients with CML were in first chronic phase. Source of hematopoetic stem cells were bone marrow (BM) in 61.9% (allo 81.5%, auto 14.8%) and peripheral blood (PB) in 38.1% (allo 18.5%, auto 85.2%). Ail donors were HLA-full matched siblings with one exception. ConditionIng regimens were BU-CY (31 pts), TBI-CY (28 pts) and Flag-lda (one pi) for leukemia, CY-ATG for AA, CBV for lymphoma and Mel-200 for MM. Median 2.69 x 108 nucieated celIsAg (BM) and 21.7 x 106 CD34 + celIsAg (PB) were infused to allo transplant recipients; 4 patients faiied to engraft and one patient was inevaluable due to early death. Acute GVHD was observed in 11 patients (16.9% - grade ll-IV in 10.7%) and chronic GVHD was documented in 18 patients (33.9%- extensive in 9.43%). VOD was seen in 8 patients (12.3%). Early response was CR in 91.6% in patienis with leukemia; patients with lymphoma showed a 73.1% response (CR & PR) rate and 23.1% had resistant disease. So far 27.6% of the patients have relapsed or showed progression and 45.7% have died (disease related 27.2%, transplant-related 18.5%). At a median follow-up time of 32 months (range 0.6-96) DFS is 50.8% and OS is 53.9% in the allo transplant group. With a shorter follow-up (median 16 months, range 1-65) the same figures for the auto transplant group are 51.9 and 55.5%, respectively, in this cohort overall, OS and DFS are significantly superior in patients with early-stage disease: 71.7% vs. 26.7% in advanced-stage disease for OS and 71.4% vs. 36.8% for DFS, respectively and this trend applies to both transplant groups (p< 0.001 for ali comparisons). PMID- 27264776 TI - Statistical methods for evaluating delirium in the ICU. PMID- 27264777 TI - Management of chronic obstructive pulmonary disease beyond the lungs. AB - Chronic obstructive pulmonary disease (COPD) is an umbrella term that covers many clinical subtypes with clearly different pulmonary and extra-pulmonary characteristics, but with persistent airflow limitation in common. This insight has led to the development of a more personalised approach in bronchodilator therapy, prevention of exacerbations, and advanced treatments (such as non invasive ventilation and lung volume reduction techniques). However, systemic manifestations and comorbidities of COPD also contribute to different clinical phenotypes and warrant an individualised approach as part of integrated disease management. Alterations in bodyweight and composition, from cachexia to obesity, demand specific management. Psychological symptoms are highly prevalent, and thorough diagnosis and treatment are necessary. Moreover, prevention of exacerbations requires interventions beyond the lungs, including treatment of gastro-oesophageal reflux disease, reduction of cardiovascular risks, and management of dyspnoea and anxiety. In this Review, we discuss the management of COPD beyond the respiratory system and propose treatment strategies on the basis of the latest research and best practices. PMID- 27264778 TI - Nano-hydroxyapatite alleviates the detrimental effects of heavy metals on plant growth and soil microbes in e-waste-contaminated soil. AB - The crude recycling activities of e-waste have led to the severe and complex contamination of e-waste workshop topsoil (0-10 cm) by heavy metals. After nano hydroxyapatite (NHAp) application in June 2013, plant and soil samples were obtained in November 2013, December 2013, March 2014 and June 2014. The results showed that NHAp effectively reduced the concentration of CaCl2-extractable Pb, Cu, Cd, and Zn in the topsoil and significantly reduced the metal content in ryegrass and also increased the plant biomass compared with that of the control. Moreover, the concentrations of CaCl2-extractable metals in the soil decreased with increasing NHAp. NHAp application also increased the activities of soil urease, phosphatase and dehydrogenase. Moreover, the soil bacterial diversity and community structure were also altered after NHAp application. Particularly, Stenotrophomonas sp. and Bacteroides percentages were increased. Our work proves that NHAp application can alleviate the detrimental effects of heavy metals on plants grown in e-waste-contaminated soil and soil enzyme activities, as well as soil microbial diversity. PMID- 27264779 TI - Evidence for spawning aggregations of the endangered Atlantic goliath grouper Epinephelus itajara in southern Brazil. AB - In this study, seasonal numerical abundance of the critically endangered Atlantic goliath grouper Epinephelus itajara was estimated by conducting scuba dive surveys and calculating sightings-per-unit-effort (SPUE) at three sites in southern Brazil. Seasonal differences in size and reproductive condition of captured or confiscated specimens were compared. The SPUE differed significantly with season, increasing in late spring and peaking during the austral summer months. A significant effect was observed in the number of fish relative to the lunar cycle. All females sampled during the summer were spawning capable, while all those sampled during other seasons were either regressing or regenerating. What these data strongly infer is that the E. itajara spawning aggregation sites have been located in the southern state of Parana and the northern state of Santa Catarina and summer is the most likely spawning season. Size frequency distributions, abundance and reproductive state were estimated and correlated with environmental variables. PMID- 27264780 TI - Noise Response Data Reveal Novel Controllability Gramian for Nonlinear Network Dynamics. AB - Control of nonlinear large-scale dynamical networks, e.g., collective behavior of agents interacting via a scale-free connection topology, is a central problem in many scientific and engineering fields. For the linear version of this problem, the so-called controllability Gramian has played an important role to quantify how effectively the dynamical states are reachable by a suitable driving input. In this paper, we first extend the notion of the controllability Gramian to nonlinear dynamics in terms of the Gibbs distribution. Next, we show that, when the networks are open to environmental noise, the newly defined Gramian is equal to the covariance matrix associated with randomly excited, but uncontrolled, dynamical state trajectories. This fact theoretically justifies a simple Monte Carlo simulation that can extract effectively controllable subdynamics in nonlinear complex networks. In addition, the result provides a novel insight into the relationship between controllability and statistical mechanics. PMID- 27264781 TI - 2-Hydroxymelatonin promotes the resistance of rice plant to multiple simultaneous abiotic stresses (combined cold and drought). AB - We investigated the physiological roles of 2-hydroxymelatonin (2-OHMel) in rice seedlings. When they were challenged with simultaneous multiple abiotic stressors, such as a combination of cold and drought, those pretreated with 2 OHMel were resistant, whereas no tolerance was observed in seedlings treated with either melatonin or water (control). The tolerance phenotype was associated with the induction of several transporter proteins, including the proton transporter (UCP1), potassium transporter (HKT1), and water channel protein (PIP2;1). Treatment with 2-OHMel increased the content of the osmoprotectant proline and maintained mitochondrial structure when plants were subjected to a combination of cold and drought stress. We screened the corresponding transcription factors (TFs) for 2-OHMel-mediated resistance to the combined stressors through analysis of large numbers of cold- and drought-related TFs. Two TFs, Myb4 and AP37, were only induced by 2-OHMel treatment. Transgenic rice lines overexpressing rice Myb4 were not resistant to the combined stressors; however, the expression of UCP1, HKT1, and PIP2;1 transcripts was slightly enhanced. These data show that 2-OHMel alleviates the effects of simultaneous abiotic stressors via the actions of multiple TFs, including Myb4 and AP37. PMID- 27264782 TI - Hepatic gene expression profiling in zebrafish (Danio rerio) exposed to the fungicide chlorothalonil. AB - Chlorothalonil (tetrachloroisophtalonitrile) is a fungicide that is widely used on agricultural crops around the world and as such, it is a ubiquitous aquatic contaminant. Despite high usage, the effects of this fungicide on non-target aquatic organisms have not been fully investigated. The aim of the present study was to (1) determine the effects of chlorothalonil toxicity on adult male zebrafish (Danio rerio) and (2) characterize the effects of chlorothalonil on gene expression patterns in the liver using two different concentrations of the fungicide, 0.007mg/L (environmentally-relevant) and 0.035mg/L (sublethal). These concentrations were selected from range-finding experiments that showed that zebrafish survival was significantly different from control animals at concentrations higher than 0.035mg/L but not below. Male zebrafish in both treatments of chlorothalonil showed a decrease in liversomatic index. A commercial D. rerio microarray (4*44K) was used to determine gene expression profiles in male zebrafish liver following a 96h toxicological assay. Microarray analysis revealed that males exposed to both 0.007mg/L or 0.035mg/L of chlorothalonil showed increased transcriptional sub-networks related to cell division and DNA damage and decreased expression of gene networks associated with reproduction, immunity, and xenobiotic clearance. This study improves knowledge regarding whole animal exposures to chlorothalonil and identifies molecular signaling cascades that are sensitive to this fungicide in the fish liver. PMID- 27264783 TI - High oxidative stress adversely affects NFkappaB mediated induction of inducible nitric oxide synthase in human neutrophils: Implications in chronic myeloid leukemia. AB - Increasing evidence support bimodal action of nitric oxide (NO) both as a promoter and as an impeder of oxygen free radicals in neutrophils (PMNs), however impact of high oxidative stress on NO generation is less explored. In the present study, we comprehensively investigated the effect of high oxidative stress on inducible nitric oxide synthase (iNOS) expression and NO generation in human PMNs. Our findings suggest that PMA or diamide induced oxidative stress in PMNs from healthy volunteers, and high endogenous ROS in PMNs of chronic myeloid leukemia (CML) patients attenuate basal as well as LPS/cytokines induced NO generation and iNOS expression in human PMNs. Mechanistically, we found that under high oxidative stress condition, S-glutathionylation of NFkappaB (p50 and p65 subunits) severely limits iNOS expression due to its reduced binding to iNOS promoter, which was reversed in presence of DTT. Furthermore, by using pharmacological inhibitors, scavengers and molecular approaches, we identified that enhanced ROS generation via NOX2 and mitochondria, reduced Grx1/2 expression and GSH level associated with NFkappaB S-glutathionylation in PMNs from CML patients. Altogether data obtained suggest that oxidative status act as an important regulator of NO generation/iNOS expression, and under enhanced oxidative stress condition, NOX2-mtROS-NFkappaB S-glutathionylation is a feed forward loop, which attenuate NO generation and iNOS expression in human PMNs. PMID- 27264784 TI - Nitrogen dioxide reducing ascorbic acid technologies in the ventilator circuit leads to uniform NO concentration during inspiration. AB - Conventional inhaled NO systems deliver NO by synchronized injection or continuous NO flow in the ventilator circuitry. Such methods can lead to variable concentrations during inspiration that may differ from desired dosing. NO concentrations in these systems are generally monitored through electrochemical methods that are too slow to capture this nuance and potential dosing error. A novel technology that reduces NO2 into NO via low-resistance ascorbic-acid cartridges just prior to inhalation has recently been described. The gas volume of these cartridges may enhance gas mixing and reduce dosing inconsistency throughout inhalation. The impact of the ascorbic-acid cartridge technology on NO concentration during inspiration was characterized through rapid chemiluminescence detection during volume control ventilation, pressure control ventilation, synchronized intermittent mandatory ventilation and continuous positive airway pressure using an in vitro lung model configured to simulate the complete uptake of NO. Two ascorbic acid cartridges in series provided uniform and consistent dosing during inspiration during all modes of ventilation. The use of one cartridge showed variable inspiratory concentration of NO at the largest tidal volumes, whereas the use of no ascorbic acid cartridge led to highly inconsistent NO inspiratory waveforms. The use of ascorbic acid cartridges also decreased breath-to-breath variation in SIMV and CPAP ventilation. The ascorbic acid cartridges, which are designed to convert NO2 (either as substrate or resulting from NO oxidation during injection) into NO, also provide the benefit of minimizing the variation of inhaled NO concentration during inspiration. It is expected that the implementation of this method will lead to more consistent and predictable dosing. PMID- 27264785 TI - Association between dietary fibre intake and fruit, vegetable or whole-grain consumption and the risk of CVD: results from the PREvencion con DIeta MEDiterranea (PREDIMED) trial. AB - Prospective studies assessing the association between fibre intake or fibre-rich food consumption and the risk of CVD have often been limited by baseline assessment of diet. Thus far, no study has used yearly repeated measurements of dietary changes during follow-up. Moreover, previous studies included healthy and selected participants who did not represent subjects at high cardiovascular risk. We used yearly repeated measurements of diet to investigate the association between fibre intake and CVD in a Mediterranean cohort of elderly adults at high cardiovascular risk. We followed-up 7216 men (55-80 years) and women (60-80 years) initially free of CVD for up to 7 years in the PREvencion con DIeta MEDiterranea study (registered as ISRCTN35739639). A 137-item validated FFQ was repeated yearly to assess diet. The primary end point, confirmed by a blinded ad hoc Event Adjudication Committee, was a composite of cardiovascular death, myocardial infarction and stroke. Time-dependent Cox's regression models were used to estimate the risk of CVD according to baseline dietary exposures and to their yearly updated changes. We found a significant inverse association for fibre (P for trend=0.020) and fruits (P for trend=0.024) in age-sex adjusted models, but the statistical significance was lost in fully adjusted models. However, we found a significant inverse association with CVD incidence for the sum of fruit and vegetable consumption. Participants who consumed in total nine or more servings/d of fruits plus vegetables had a hazard ratio 0.60 (95 % CI 0.40, 0.96) of CVD in comparison with those consuming <5 servings/d. PMID- 27264786 TI - In vitro experimental environments lacking or containing soil disparately affect competition experiments of Aspergillus flavus and co-occurring fungi in maize grains. AB - In vitro experimental environments are used to study interactions between microorganisms, and to predict dynamics in natural ecosystems. This study highlights that experimental in vitro environments should be selected to match closely the natural environment of interest during in vitro studies to strengthen extrapolations about aflatoxin production by Aspergillus and competing organisms. Fungal competition and aflatoxin accumulation were studied in soil, cotton wool or tube (water-only) environments, for Aspergillus flavus competition with Penicillium purpurogenum, Fusarium oxysporum or Sarocladium zeae within maize grains. Inoculated grains were incubated in each environment at two temperature regimes (25 and 30 degrees C). Competition experiments showed interaction between the main effects of aflatoxin accumulation and the environment at 25 degrees C, but not so at 30 degrees C. However, competition experiments showed fungal populations were always interacting with their environments. Fungal survival differed after the 72-h incubation in different experimental environments. Whereas all fungi incubated within the soil environment survived, in the cotton wool environment none of the competitors of A. flavus survived at 30 degrees C. With aflatoxin accumulation, F. oxysporum was the only fungus able to interdict aflatoxin production at both temperatures. This occurred only in the soil environment and fumonisins accumulated instead. Smallholder farmers in developing countries face serious mycotoxin contamination of their grains, and soil is a natural reservoir for the associated fungal propagules, and a drying and storage surface for grains on these farms. Studying fungal dynamics in the soil environment and other environments in vitro can provide insights into aflatoxin accumulation post-harvest. PMID- 27264787 TI - Integration of Nine Steps into One Membrane Reactor To Produce Synthesis Gases for Ammonia and Liquid Fuel. AB - The synthesis of ammonia and liquid fuel are two important chemical processes in which most of the energy is consumed in the production of H2 /N2 and H2 /CO synthesis gases from natural gas (methane). Here, we report a membrane reactor with a mixed ionic-electronic conducting membrane, in which the nine steps for the production of the two types of synthesis gases are shortened to one step by using water, air, and methane as feeds. In the membrane reactor, there is no direct CO2 emission and no CO or H2 S present in the ammonia synthesis gas. The energy consumption for the production of the two synthesis gases can be reduced by 63 % by using this membrane reactor. This promising membrane reactor process has been successfully demonstrated by experiment. PMID- 27264788 TI - Oxygen-Deficient Zirconia (ZrO2-x): A New Material for Solar Light Absorption. AB - Here, we present oxygen-deficient black ZrO2-x as a new material for sunlight absorption with a low band gap around ~1.5 eV, via a controlled magnesiothermic reduction in 5% H2/Ar from white ZrO2, a wide bandgap(~5 eV) semiconductor, usually not considered for solar light absorption. It shows for the first time a dramatic increase in solar light absorbance and significant activity for solar light-induced H2 production from methanol-water with excellent stability up to 30 days while white ZrO2 fails. Generation of large amounts of oxygen vacancies or surface defects clearly visualized by the HR-TEM and HR-SEM images is the main reason for the drastic alteration of the optical properties through the formation of new energy states near valence band and conduction band towards Fermi level in black ZrO2-x as indicated by XPS and DFT calculations of black ZrO2-x. Current reduction method using Mg and H2 is mild, but highly efficient to produce solar light-assisted photocatalytically active black ZrO2-x. PMID- 27264789 TI - Transcriptomic and molecular genetic analysis of the cell wall salvage response of Aspergillus niger to the absence of galactofuranose synthesis. AB - The biosynthesis of cell surface-located galactofuranose (Galf)-containing glycostructures such as galactomannan, N-glycans and O-glycans in filamentous fungi is important to secure the integrity of the cell wall. UgmA encodes an UDP galactopyranose mutase, which is essential for the formation of Galf. Consequently, the DeltaugmA mutant lacks Galf-containing molecules. Our previous work in Aspergillus niger work suggested that loss of function of ugmA results in activation of the cell wall integrity (CWI) pathway which is characterized by increased expression of the agsA gene, encoding an alpha-glucan synthase. In this study, the transcriptional response of the DeltaugmA mutant was further linked to the CWI pathway by showing the induced and constitutive phosphorylation of the CWI-MAP kinase in the DeltaugmA mutant. To identify genes involved in cell wall remodelling in response to the absence of galactofuranose biosynthesis, a genome wide expression analysis was performed using RNAseq. Over 400 genes were higher expressed in the DeltaugmA mutant compared to the wild-type. These include genes that encode enzymes involved in chitin (gfaB, gnsA, chsA) and alpha-glucan synthesis (agsA), and in beta-glucan remodelling (bgxA, gelF and dfgC), and also include several glycosylphosphatidylinositol (GPI)-anchored cell wall protein encoding genes. In silico analysis of the 1-kb promoter regions of the up regulated genes in the DeltaugmA mutant indicated overrepresentation of genes with RlmA, MsnA, PacC and SteA-binding sites. The importance of these transcription factors for survival of the DeltaugmA mutant was analysed by constructing the respective double mutants. The DeltaugmA/DeltarlmA and DeltaugmA/DeltamsnA double mutants showed strong synthetic growth defects, indicating the importance of these transcription factors to maintain cell wall integrity in the absence of Galf biosynthesis. PMID- 27264790 TI - Percutaneous radiofrequency ablation of renal tumors in high-risk patients: 10 years' experience. AB - OBJECTIVE: To retrospectively evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) done to treat renal tumors in patients with high surgical risk or with the risk of developing multiple renal tumors in the medium term at our center over a period of 10 years. MATERIAL AND METHODS: Between 2005 and 2015, we used RFA to treat 89 T1a or T1b tumors in 87 patients (mean age, 73.7+/-10.87 years) with high surgical risk. We excluded patients treated with radiofrequency and embolization or microwave ablation. The tumors treated were clear cell carcinomas (43.6%), papillary renal carcinomas (17.2%), chromophobe renal cell carcinomas (10.3%), cystic tumors (2.2%), and an angiomyolipoma (1.1%). The mean size of the tumors was 2.6cm. Computed tomography and/or ultrasonography were used to guide the procedure. We analyzed the relation between the efficacy of the procedure and patients' age, the type of needle, the source of the patients, the size and location of the tumor, and the number of sessions required to achieve ablation. We recorded all complications. RESULTS: The RFA procedure was completed in all patients. The mean follow-up period was 32.1 months. The efficacy was 93.7%. A single session was sufficient in 87.5% of patients; 8% required two sessions and 4.5% required three sessions. The only factor associated with worse efficacy was the size of the tumor (p=0.03). The rate of complications was 5.6%. CONCLUSIONS: RFA is efficacious and safe, with results comparable to those reported in the literature. PMID- 27264791 TI - NanoARPES of twisted bilayer graphene on SiC: absence of velocity renormalization for small angles. AB - The structural and electronic properties of twisted bilayer graphene (TBG) on SiC(000) grown by Si flux-assisted molecular beam epitaxy were investigated using scanning tunneling microscopy (STM) and angle-resolved photoelectron spectroscopy with nanometric spatial resolution. STM images revealed a wide distribution of twist angles between the two graphene layers. The electronic structure recorded in single TBG grains showed two closely-spaced Dirac pi bands associated to the two stacked layers with respective twist angles in the range 1-3 degrees . The renormalization of velocity predicted in previous theoretical calculations for small twist angles was not observed. PMID- 27264792 TI - Knowing so much, yet knowing so little: a scoping review of interventions that address the stigma of mental illness in the Canadian context. AB - Stigma can have detrimental effects on the health and wellbeing of individuals living with a mental illness. This scoping review describes the nature, range, and extent of intervention research aimed at reducing public and self-stigma of mental illness in the Canadian context. The review was guided by Arksey and O'Malley's framework. A search of databases and relevant websites identified 35 primary studies. Most studies used quantitative research methods and included predominantly youth or middle-aged adults, women, and white Canadian-born people. Guided by different conceptualizations of stigma, direct or indirect contact, education, and advocacy-focused interventions, aimed to provide information, and/or develop skills to address self and public stigma. Most studies evaluated interventions' effectiveness short-term. Of the few studies that followed-up participants long-term, some were able to reduce stigmatizing attitudes post intervention, however, these targeted only specific groups such as students or health care professionals. Lack of diversity among the samples, and limited evidence of long-term effectiveness of interventions, were some of the studies' limitations. What is currently known about interventions aimed at reducing the stigma of mental illness in the Canadian context is not informed by research among vulnerable groups, such as people living with a mental illness, older adults, immigrants, and people of diverse ethnic backgrounds. Interventions that are informed by clear conceptualizations of stigma and rigorously evaluated in a range of ethno-cultural groups would create a knowledge base that is useful for policy-makers, community leaders, and agencies serving various ethnic communities in Canada. PMID- 27264793 TI - Coadministration of ticagrelor and ritonavir: Toward prospective dose adjustment to maintain an optimal platelet inhibition using the PBPK approach. AB - Ticagrelor is a potent antiplatelet drug metabolized by cytochrome (CYP)3A. It is contraindicated in patients with human immunodeficiency virus (HIV) because of the expected CYP3A inhibition by most protease inhibitors, such as ritonavir and an increased bleeding risk. In this study, a physiologically based pharmacokinetic (PBPK) model was created for ticagrelor and its active metabolite (AM). Based on the simulated interaction between ticagrelor 180 mg and ritonavir 100 mg, a lower dose of ticagrelor was calculated to obtain, when coadministered with ritonavir, the same pharmacokinetic (PK) and platelet inhibition as ticagrelor administered alone. A clinical study was thereafter conducted in healthy volunteers. Observed PK profiles of ticagrelor and its AM were successfully predicted with the model. Platelet inhibition was nearly complete in both sessions despite administration of a fourfold lower dose of ticagrelor in the second session. This PBPK model could be prospectively used to broaden the usage of ticagrelor in patients with ritonavir-treated HIV regardless of the CYP3A inhibition. PMID- 27264802 TI - The time for individualizing blood pressure goals has arrived. PMID- 27264803 TI - The mass mortality of blue mussels (Mytilus spp.) from the Atlantic coast of France is associated with heavy genomic abnormalities as evidenced by flow cytometry. AB - Since 2014, France's blue mussel industry has been facing heavy mortality outbreaks (90-100%) affecting both juveniles and adults. This report presents evidence of heavy genomic abnormalities associated with mortality outbreaks in blue mussels, Mytilus edulis-galloprovincialis, from the Atlantic coast of France. In this study, ploidy characteristics of hemic cells were investigated using Flow CytoMetry (FCM), revealing an unusual, broad continuum of ploidy distribution from hypodiploidy to tetraploidy. FCM was additionally used to evaluate, at individual and populations levels, different thresholds of genomic abnormality (GA%) using the percentage of non-diploid nuclei. Individual mussels were considered to be abnormal when more than 10% of hemocytes in S-G2/M phase were present. At the population level, a threshold of 6% for the mean intensity of the abnormality is proposed, which means in the population, more than 6% of individual mussels have to present with more than 10% of their hemocytes in S G2/M phase. GA% was found to be significantly predictive of the final mortality. Based on the established thresholds, only two mussel stocks analyzed in this study were considered to have good cytogenetic quality, while all other stocks appeared to be affected. FCM offers a very powerful tool to help manage current blue mussel mortality in France. We also believe that annual and extensive determination of cytogenetic quality of wild and cultivated mussel beds along with exclusive use of FCM-qualified mussel seeds should be a priority. PMID- 27264804 TI - [ZRS mutations in two Chinese Han families featuring triphalangeal thumbs and preaxial polydactyly]. AB - OBJECTIVE: To identify the causative mutations in two Chinese Han families featuring triphalangeal thumbs (TPT) and preaxial polydactyly (PPD). METHODS: Blood samples were collected from 9 members (2 affected) from family 1 and 14 members (7 affected) from family 2. After genomic DNA was extracted, the ZPA regulatory sequence (ZRS) region was analyzed with real-time quantitative PCR (qPCR) and Sanger sequencing. For family 1, haplotypes compassing the ZRS were also analyzed with short tandem repeats (STR) and single nucleotide changes. RESULTS: No copy number mutation around the ZRS region was found in both families. Two heterogeneous mutations in the ZRS (406A>G and 105C>G) were found to co-segregate with the TPT/PPD malformation in family 1 and 2, respectively. Neither mutation was detected in 200 healthy individuals. Haplotype analysis and Sanger sequencing of family 1 indicated that the first TPT/PPD patient in the family was both germline and somatic mosaic for the 406A>G mutation. CONCLUSION: Two pathogenic ZRS mutations, 105C>G and 406A>G, have been identified in two Chinese Han families with TPT/PPD, among which the 406A>G mutation was de novo. PMID- 27264805 TI - [Analysis of clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency]. AB - OBJECTIVE: To investigate the clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency (BKTD). METHODS: Clinical features and laboratory test data were collected. The probands were monozygotic twin brothers. Genomic DNA was isolated from peripheral blood leukocytes obtained from the probands and their family members. Molecular genetic testing of the ACAT1 gene was carried out. RESULTS: The probands have presented with fever, vomiting and severe ketoacidosis. By arterial blood gas testing, pH was determined to be 7.164, bicarbonate was 4.0 mmol/L, and urine ketone was ++++. Urinary organic acid gas chromatography-mass spectrometry analysis showed excessive excretion of 3-hydroxybutyric acid, 2-methyl-3-hydroxybutyric acid and tiglylglycine. Increased 3-hydroxybutyrylcarnitine (C4-OH), tiglylcarnitine(C5:1) and 3-hydroxyisovalerylcarnitine (C5-OH) levels. The clinical phenotype of proband's parents were both normal, but an elder sister turned out to be an affected patient. Genetic analysis has identified two heterozygous mutations [c.622C>T(p.R208X) and c.653C>T (p.S218F)] in the proband, which were respectively detected in the mother and father. The c.653C>T (p.S218F) mutation was not found among the 100 healthy controls and has not been included in the Human Gene Mutation Database(HGMD). CONCLUSION: The primary clinical manifestations of BKTD is ketoacidosis. Urine organic acid and blood acylcarnitine analyses play an important role in the diagnosis of the disease. The compound heterozygous of ACAT1 gene mutations probably underlie the BKTD in our patient. PMID- 27264806 TI - [Two novel pathogenic mutations of GAN gene identified in a patient with giant axonal neuropathy]. AB - OBJECTIVE: To explore the disease-causing mutations in a patient suspected for giant axonal neuropathy(GAN). METHODS: Target sequence capture sequencing was used to screen potential mutations in genomic DNA extracted from peripheral blood sample of the patient. Sanger sequencing was applied to confirm the detected mutation. The mutation was verified among 400 GAN alleles from 200 healthy individuals by Sanger sequencing. The function of the mutations was predicted by bioinformatics analysis. RESULTS: The patient was identified as a compound heterozygote carrying two novel pathogenic GAN mutations, i.e., c.778G>T (p.Glu260Ter) and c.277G>A (p.Gly93Arg). Sanger sequencing confirmed that the c.778G>T (p.Glu260Ter) mutation was inherited from his father, while c.277G>A (p.Gly93Arg) was inherited from his mother. The same mutations was not found in the 200 healthy individuals. Bioinformatics analysis predicted that the two mutations probably caused functional abnormality of gigaxonin. CONCLUSION: Two novel GAN mutations were detected in a patient with GAN. Both mutations are pathogenic and can cause abnormalities of gigaxonin structure and function, leading to pathogenesis of GAN. The results may also offer valuable information for similar diseases. PMID- 27264807 TI - [Homozygous missense mutation p.Val298Met of F10 gene causing hereditary coagulation factor X deficiency in a Chinese pedigree]. AB - OBJECTIVE: To identify potential mutation underlying coagulation factor X (FX) deficiency in a consanguineous Chinese pedigree. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FX activity (FX:C) and other coagulant parameters were determined with a one-stage clotting assay. The FX antigen (FX:Ag) was determined with an ELISA assay. All coding exons and exon intron boundaries of the F10 gene were amplified with PCR and subjected to direct sequencing. Suspected mutation was confirmed by reverse sequencing and analyzed with CLC Genomics Workbench 7.5 software. RESULTS: The PT and APTT in the proband were prolonged to 67.2 s and 102.9 s, respectively. Further study showed that her FX:C and FX:Ag were reduced by 1% and 8%, respectively. The PT of her father, mother, and little brother were slightly prolonged to 14.5 s, 14.4 s and 14.4 s, respectively. The FX:C and FX:Ag in her father, mother and little brother were all slightly reduced. Genetic analysis of the proband has revealed a homozygous G>A change at nucleotide 27881 in exon 8 of the F10 gene, which predicted a p.Val298Met substitution. The proband's father, mother, and little brother were all heterozygous for the p.Val298Met mutation. The proband has inherited the homozygous mutation from her parents by consanguineous marriage. Other family members were all normal. Bioinformatics analysis has indicated that this mutation may result in changes in the secondary structure of the FX protein. CONCLUSION: A homozygous mutation g.27881G>A(p.Val298Met) of the F10 gene has been identified, which probably accounts for the low FX concentrations in this pedigree. PMID- 27264808 TI - [Genotype and phenotype correlation of phenylalanine hydroxylase deficiency among patients from Henan]. AB - OBJECTIVE: To delineate the mutation spectrum of phenylalanine hydroxylase (PAH) gene among patients affected with phenylalanine hydroxylase deficiency (PAHD) in Henan Province of China, and to explore the correlation between the genotype and the phenotype. METHODS: A total of 155 affected children were recruited. Potential mutation of the PAH gene were analyzed by direct sequencing. The genotype-phenotype correlation was analyzed by matching the expected and observed phenotypes. RESULTS: Over 72 mutations and 108 genotypes have been identified. There were 7 homozygous mutations, including 1 case with EX6-96A>G/EX6-96A>G, 1 with R241C/R241C, 1 with R413P/R413P, and 4 with R243Q/R243Q. Among these, 6 patients have presented classic PKU phenotypes, except for a R241C/R241C genotype which has led to mild PKU. In 104 patients carrying compound PAH mutations, 52 were classic, 34 were mild and 39 had mild HPA. Patients who were heterozygous for EX6-96A>G/R241C, R243Q/A434D, EX6-96A>G/R413P and EX6-96A>G/ R241C were found with both the classic PKU and mild PKU phenotypes. Common mutations associated with mild HPA have included R53H, R243Q, V399V and H107R. The common mutations associated with mild PKU included R243Q, R241C, EX6-96A>G, and IVS4-1G>A. The prevalent mutations in classic PKU were R243Q, EX6-96A>G and V399V. The consistency between prediction of the biochemical genotype and observed phenotype was 77.78%, especially in classic PKU, the consistency was up to 82.14%. Significant correlations were disclosed between pretreatment levels of phenylalanine and AV sum (r=-0.6729, P < 0.01). CONCLUSION: The mutation spectrum of PAH gene in Henan seems to differ from that of other regions. Independent assortment of mutant alleles may result in a complex genotype-phenotype correlation, but the genotypes of PAHD patients have correlated with the phenotype. PMID- 27264809 TI - [Application of chromosome microarray analysis for patients with skeletal anomalies and a normal karyotype]. AB - OBJECTIVE: To analyze patients with skeletal anomalies (SA) but a normal karyotype using chromosome microarray analysis (CMA). METHODS: From June 2012 to May 2015, 43 children found to have skeletal anomalies with or without other abnormalities were subjected to karyotyping analysis. For those with a normal karyotype, DNA was extracted and hybridized with Affymetrix CytoScan 750 kb arrays following the manufacturer's protocol. The results were analyzed with CHAS v2.0 software. RESULTS: Two patients (4.65%) were detected with an abnormal karyotype. The remaining 41 patients with a normal karyotype were classified into 3 groups: isolated SA (n=17), SA with mental retardation (n=6), and SA with other structural anomalies (n=18). Clinically significant copy number variations (CNVs) were found in 21.95% (9/41) of the cases, which included 17.65% (3/17) with isolated SA, 33.33% (2/6) with SA and mental retardation, and 22.22% (4/18) of SA with other structural deformities. CONCLUSION: Whole-genome CMA can detect clinically significant CNVs which may not be found by conventional karyotyping analysis and increase the detection rate by approximately 21.95%. It may be recommended for patients with SA but a normal karyotype. PMID- 27264810 TI - [Mutation analysis of seven patients with Waardenburg syndrome]. AB - OBJECTIVE: To perform genetic analysis for 7 patients with Waardenburg syndrome. METHODS: Potential mutation of MITF, PAX3, SOX10 and SNAI2 genes was screened by polymerase chain reaction and direct sequencing. Functions of non-synonymous polymorphisms were predicted with PolyPhen2 software. RESULTS: Seven mutations, including c.649-651delAGA (p.R217del), c.72delG (p.G24fs), c.185T>C (p.M62T), c.118C>T (p.Q40X), c.422T>C (p.L141P), c.640C>T (p.R214X) and c.28G>T(p.G43V), were detected in the patients. Among these, four mutations of the PAX3 gene (c.72delG, c.185T>C, c.118C>T and c.128G>T) and one SOX10 gene mutation (c.422T>C) were not reported previously. Three non-synonymous SNPs (c.185T>C, c.128G>T and c.422T>C) were predicted as harmful. CONCLUSION: Genetic mutations have been detected in all patients with Waardenburg syndrome. PMID- 27264811 TI - [Identification of a novel MLC1 mutation in a Chinese patient affected with megalencephalic leukoencephalopathy with subcortical cysts]. AB - OBJECTIVE: To detect potential mutation of MLC1 gene in a child affected with megalencephalic leukoencephalopathy with subcortical cysts (MLC). METHODS: Clinical symptoms of the patient were retrieved. Peripheral blood DNA samples from the patient, her parents and healthy controls were collected. Potential mutation of the MLC1 gene was detected by polymerase chain reaction and Sanger sequencing. RESULTS: The patient presented with severe motor developmental delay and a giant skull. Magnetic resonance scan showed diffuse white matter swelling in bilateral hemispheres. DNA sequencing identified a novel homozygous c.177 c.180delC mutation of the MLC1 gene. The parents of the patient both carried a heterozygous mutation c.177-c.180delC but had a normal phenotype. CONCLUSION: A novel MLC1 mutation c.177-c.180delC has been identified in a patient with MLC. The mutation is presumably disease-causing and has derived from parents who are both carriers. PMID- 27264812 TI - [Seminal plasma miR-122-3p and miR-141-5p stability and its diagnosis value for idiopathic asthenospermia]. AB - OBJECTIVE: To explore the stability of seminal plasma miR-122-3p and miR-141-5p and their diagnostic value for idiopathic asthenospermia. METHODS: Seminal plasma miR-122-3p and miR-141-5p with various incubation time, freeze-thaw cycles and incubation time were analyzed. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used to detect the content of miR-122-3p and miR-141 5p, with U6 snRNA as the reference. The idiopathic asthenospermia group was further divided into grade I and II based on the progressive motility percent, and the content of miR-122-3p and miR-141-5p in the two grades were compared. RESULTS: No difference was detected after incubation at room temperature and 4 degrees Celsius. But seminal plasma miR-122-3p and miR-141-5p have decreased along with the increase in freeze-thaw cycles increases. RT-PCR assayed showed that the miR-122-3p content in the idiopathic asthenospermia group was significantly lower than the control group, while miR-141-5p was significantly higher. The difference in both miR-122-3p and miR-141-5p content was statistically significant (P < 0.05). A significant difference in miR-122-3p and miR-141-5p content between a and b groups was also detected (P < 0.05). The AUC ROC of miR-122-3p was 0.88. At the cutoff value of 1.02, the sensitivity and specificity was 83% and 84%, respectively. At the cutoff of 2.95, the AUC-ROC of miR-141-5p was 0.88. The sensitivity and specificity was 84% and 70%, respectively. CONCLUSION: MiR-122-3p and miR-141-5p in seminal plasma are stable and have certain value for the diagnosis of idiopathic asthenospermia. PMID- 27264813 TI - [Mutation analysis of presenilin 1 gene in a Chinese family affected with early onset familial Alzheimer's disease]. AB - OBJECTIVE: To explore the clinical phenotype and genotype in a Chinese family affected with early-onset familial Alzheimer's disease (EOFAD). METHODS: Potential mutation of beta-amyloid precursor protein (APP) gene, presenilin 1 (PSEN1) gene and apolipoprotein E (APOE) gene was detected with polymerase chain reaction (PCR) and direct sequencing. RESULTS: Homozygous APOE epsilon 2 allele and no gene mutation of APP gene were detected in the proband (III1). A 488A>G mutation (His163Arg) of the PSEN1 gene was found in the proband and other 4 family members (IV1, IV12, IV21, V2). CONCLUSION: A mutation (c.488A>G, p.His163Arg) of PSEN1 gene was found in a Chinese family affected with EOFAD. PMID- 27264814 TI - [Genetic analysis of a child affected with Crigler-Najjar syndrome type II]. AB - OBJECTIVE: To detect potential mutation of the UGT1A1 gene in a child affected with Crigler-Najjar syndrome type II. METHODS: Blood samples were collected from the patient and his parents for the extraction of genomic DNA. Potential mutation of the UGT1A1 gene was detected with polymerase chain reaction (PCR) and direct sequencing. The child was followed up until the age of 3 years and 6 months. RESULTS: The patient showed persistent unconjugated hyperbilirubinemia. Sequencing of the UGT1A1 gene has detected a rare heterozygous c.610 A>G (p.Met204Val) mutation in the exon 1, in addition with a heterozygous c.1091 C>T (p.Pro364Leu) mutation in exon 4. The two mutations were inherited from his father and mother, respectively. The patient was diagnosed with Crigler-Najjar syndrome type II and received oral phenobarbital treatment. CONCLUSION: The compound UGT1A1 gene mutation probably accounts for the disease in the patient manifesting persistent mild unconjugated hyperbilirubinemia. Genetic counseling and prenatal diagnosis should be provided for his family. PMID- 27264815 TI - [SNP array and cytogenetic analysis of a patient with unexplained mental retardation]. AB - OBJECTIVE: To analyze a patient with unexplained mental retardation by using three primer PCR (TP-PCR) and single nucleotide polymorphisms array (SNP-array), and to correlate the genotype with phenotype. METHODS: Peripheral blood sample was taken from the patient for the extraction of DNA. TP-PCR was used to determine the copy number of CGG repeats in the 5'UTR of the FMR1 gene. SNP array was used for high resolution analysis of the patient's genome. RESULTS: TP-PCR has shown no abnormal amplification of CGG in the 5'UTR of FMR1 gene. Hence, Fragile X syndrome was excluded as the cause for mental retardation. SNP array analysis has identified a 0.93 Mb duplication at 7q36.1-q36.2 and a 2.2 Mb deletion at 12p13.1-p13.2 in the patient. CONCLUSION: The microduplication and microdeletion discovered in the patient probably underlies the intelligence disability. The high-resolution SNP array can provide accurate information for the identification of pathogenesis, and is the preferred method for the diagnosis of unexplained mental retardation. PMID- 27264816 TI - [Genetic analysis for 2 females carrying idic(Y)(p) and with sex development disorders]. AB - OBJECTIVE: To investigate the phenotype-genotype association of isodicentromere Y chromosome by analysis of two female patients carrying the chromosome with sexual development disorders. METHODS: The karyotypes of the two patients were determined by application of conventional G banding of peripheral blood samples and fluorescence in situ hybridization (FISH). PCR was applied to detect the presence of SRY gene. RESULTS: Conventional karyotype analysis showed case 1 to be a mosaic: mos.45,X[38]/46,X,+mar[151]/47,XY,+mar[5]/47,X,+mar * 2[2]/46,XY[4], FISH showed that 12 different cell lines were presented in the karyotype of case 1 and partial cell lines with SRY gene, the marker is an isodicentromere Y chromosome [idic(Y)(p)]. No mutation was found in the SRY gene. The karyotype of case 2 was mos.45,X[25]/46,X,+mar[35]. FISH showed the marker to be an idic(Y)(p) without the SRY gene. CONCLUSION: The karyotype of patients carrying idic(Y)(p) seems unstable, and female patients have the characteristics of short stature and secondary sexual hypoplasia. Karyotype analysis combined with FISH analysis can accurately determine the breakpoint of idic(Y) and identify the types of complex mosaic, which may facilitate genetic counseling and prognosis. PMID- 27264817 TI - [Genetic analysis of a fetus with partial 1q monosomy and partial 17q trisomy]. AB - OBJECTIVE: To analyze a fetus with abnormal sonographic features and correlated its genotype with phenotype. METHODS: G-banding analysis, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed for the fetus. Karyotyping and FISH were also carried out for the parents. RESULTS: SNP array detected a 4.4 Mb deletion at 1q44 and a 10.4 Mb duplication at 17q24.3q25.3 in the fetus. Based on the results of SNP array and FISH analysis, the father was diagnosed with a cryptic t(1;17)(q44;q24.3) translocation. The fetus has inherited a der(1)t(1;17)(q44;q24.3) from its father. CONCLUSION: The 1q44 deletion and 17q24.3q25.3 duplication may have contributed to the abnormal sonographic features presented by the fetus. PMID- 27264818 TI - [Pathogenetic mechanism for a female patient with hemophilia A]. AB - OBJECTIVE: To explore the pathogenetic mechanism for a female patient affected with hemophilia A (HA). METHODS: Potential genetic defect was detected with inverse shifting-polymerase chain reaction (IS-PCR). The pattern of X chromosome inactivation was determined with a human androgen receptor assay (HUMARA assay). G-banded karyotyping was carried out to exclude potential chromosome aberrations. RESULTS: IS-PCR showed that the defect of FVIII gene was the distal type of intron 22 inversion. The HUMARA assay showed that the X chromosome inactivation was non-random, and that the mother's X chromosome activity was lower than that of the father's X chromosome which has carried the inverted FVIII gene. No abnormalities were found with G-banded chromosomes. CONCLUSION: The prevalence of female HA patient may be caused by non-random inactivation of X chromosomes. PMID- 27264819 TI - [Genetic analysis of a rare case with Kallman syndrome and steroid sulfatase deficiency]. AB - OBJECTIVE: To explore the pathogenesis of a patient featuring azoospermia and steroid sulfatase deficiency. METHODS: Polymerase chain reaction (PCR), G-banded karyotyping and Illumina Human CytoSNP-12 Beadchip analysis were conducted. RESULTS: STS sites PCR showed that there was no deletion in the AZF zone. G banding analysis indicated an unknown structural change in chromosome X, which was verified by single nucleotide polymorphism array (SNP array) as a 5.4 Mb deletion in Xp22.31-p22.33. CONCLUSION: The Xp22.31-p22.33 deletion probably underlies the Kallman syndrome and steroid sulfatase defect in the patient. PMID- 27264820 TI - [Prenatal diagnosis of 1p36.3 microdeletion in a fetus with complex heart defect]. AB - OBJECTIVE: To analyze a fetus presenting with complex heart defect and assess the recurrence risk. METHODS: Conventional karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism-based array (SNP-array) were used to analyze the fetus and his parents. RESULTS: SNP-array has detected a 6.9 Mb microdeletion at 1p36.33-p36.23 in the fetus. Chromosomal and FISH analyses indicated that the father of the fetus had a karyotype of 46,XY,t(1;14)(p36.3;p12), and that the fetus has inherited an abnormal chromosome 1 derived from the paternal translocation. CONCLUSION: SNP-array combined with GTG banding and FISH can help to detect cryptic translocation, microdeletion or microduplication of chromosomes and is valuable to assess the recurrence risk for the affected family. PMID- 27264821 TI - [Mutation analysis and prenatal diagnosis for a family affected with congenital factor VII deficiency]. AB - OBJECTIVE: To provide mutation analysis and prenatal diagnosis for a family affected with congenital factor VII(FVII) deficiency. METHODS: DNA was extracted from peripheral blood samples from the proband and his parents. All exons and flanking sequence of the FVII gene were amplified with PCR and subjected to direct sequencing. Prenatal diagnosis was performed by amniocentesis. RESULTS: A homozygous mutation (NM_000131.3) c.572-1G>A was identified in the proband. Both parents of the fetus were carriers of the mutation. CONCLUSION: A method for molecular diagnosis of congenital factor VII deficiency was established and successfully applied for an affected family. PMID- 27264822 TI - [Phenotypic and genetic analysis of a child featuring multiple malformations due to chromosome 14q deletion]. AB - OBJECTIVE: To analyze a child with mental retardation, growth retardation and language development disorders. METHODS: Conventional G-banding analysis was performed on chromosomes cultivated from peripheral blood samples derived from the child and her parents. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities, and the result was confirmed by short tandem repeats (STR) analysis. RESULTS: For the child and her parents, no karyotypic abnormality was detected. However, aCGH analysis has identified a 14q22.1 deletion in the child. The microdeletion, with a size of 2.9 Mb was confirmed by STR analysis. CONCLUSION: The 2.9 Mb chromosomal microdeletion probably underlies the mental retardation, growth retardation and language development disorders in the child. PMID- 27264823 TI - [Association of polymorphisms of miRNA biogenesis related genes DICER and DROSHA with azoospermia]. AB - OBJECTIVE: To assess the association of polymorphisms of miRNA biogenesis related genes DICER and DROSHA with azoospermia. METHODS: For 330 patients with primary azoospermia and 282 fertile male controls, single nucleotide polymorphisms (SNPs) of DICER rs3742330 and DROSHA rs10719 were determined with a restriction fragment length polymorphism (RFLP) method. RESULTS: For the SNP rs3742330, the frequency of A allele was higher among azoospermia patients compared with the controls (72.0% vs.64.4%, P=0.004), and so was the frequency of AA genotype (53.0% vs. 41.8%, P=0.027, OR=1.829, 95%CI: 1.071-3.124). On the other hand, the allelic and genotypic frequencies of rs10719 did not differ between the two groups (all P > 0.05). CONCLUSION: Polymorphisms of rs3742330 of the DICER gene, particularly the AA genotype, may be associated with azoospermia. PMID- 27264824 TI - [Significance of clonal TCR gene rearrangement in acquired pure red cell aplastic anemia]. AB - OBJECTIVE: To evaluate the significance of T-cell antigen receptor (TCR) gene rearrangement among patients with acquired pure red cell aplastic anemia (A PRCA). METHODS: For 16 patients with A-PRCA, an immunosuppressive regimen based on cyclosporin A (CsA) was applied. Rearrangement of the TCR gene was detected by PCR, and T lymphocyte subsets in peripheral blood specimens was detected with flow cytometry. RESULTS: Five patients had presented with TCR clonal rearrangement and were positive for both TCR gamma and TCR delta. The blood of 13 patients have returned to normal with the treatment, which included 3 cases with bone marrow returning to normal. In 7 cases, the red cell hyperplasia of bone marrow is still down, but has increased with the treatment. Three patients were close to cure, 7 showed remission, 3 were improved, but 3 were ineffective. The rate of effective treatment in those with TCR rearrangement (2/5) was significantly lower than that those without (11/11, chi-square=8.123, P < 0.05). Compared with those without the TCR gene rearrangement, the Th cells and proportion of Th/Ts were significantly lower, while the Ts cell (CD3+CD8+) were significantly higher in those with the rearrangement (P < 0.05). CONCLUSION: TCR gene rearrangement may play a role in the pathogenesis of A-PRCA. CsA is effective for the treatment of A-PRCA, but patients presenting clonal TCR gene rearrangement may response poorly to the treatment. PMID- 27264826 TI - [Association of extracellular superoxide dismutase gene methylation with cerebral infarction]. AB - OBJECTIVE: To assess the association of extracellular superoxide dismutase (EC SOD) gene methylation with cerebral infarction. METHODS: Eighty-three patients with cerebral infarction and 94 healthy controls were enrolled. Based on cerebral MR findings, the size of infarction, extent of intracranial atherosclerosis, the National Institutes of Health Stroke Scale (NIHSS) score, and Barthel index were calculated. Methylation-specific PCR was used to analyze the methylation status of the EC-SOD gene in peripheral blood samples and its correlation with cerebral infarction. RESULTS: The rate of EC-SOD gene promoter region methylation of the cerebral infarction group was lower than that of the control group (30.1% vs. 53.2%, P < 0.05). Patients with larger area of cerebral infarction (>4 cm in diameter) showed a lower methylation rate than those with a smaller cerebral infarction (0 vs. 39.1%, P < 0.05). Based on their cerebral MRA, 57 patients were divided into none, mild, moderate, and severe cerebral arteriosclerosis groups. The rate of EC-SOD gene methylation of the four groups showed a downward trend (at 45.5%, 42.9%, 23.8%, and 14.3%, respectively), though no statistical significance was found (P > 0.05). For the cerebral infarction group, those with higher rate of methylation had lower NIHSS scores (P < 0.05) but insignificantly higher Barthel index (P > 0.05). CONCLUSION: The EC-SOD methylation frequency of case group was lower than the control group. The methylation status is associated with the size of cerebral infarction, degree of cerebral arteriosclerosis and severity of neurological impairment. PMID- 27264825 TI - [Association of AIRE gene polymorphisms with susceptibility to rheumatoid arthritis among ethnic Han Chinese from Shaanxi]. AB - OBJECTIVE: To assess the association of AIRE gene polymorphisms with rheumatoid arthritis (RA) among ethnic Han Chinese from Shaan'xi Province. METHODS: Genomic DNA was prepared from 384 individuals with RA and 576 healthy controls. Four tag single nucleotide polymorphisms (SNP) in the AIRE gene (rs2075876, rs760426, rs1800520, and rs878081) were genotyped with a SNaPshot method. The genotypic and allelic frequencies were evaluated using a Chi square test. Genotyping data was corrected by Logistic regression for age and gender. The linkage disequilibrium (LD) block structure was examined using Hapview 4.2 software. RESULTS: All 4 SNPs have conformed to Hardy-Weinberg equilibrium (P > 0.05). Two SNPs were significantly associated with RA, which included G allele of rs2075876 (OR=1.41, 95% CI: 1.17-1.71, P=3.7 * 10(-4)); Dominant model (OR=1.79, 95% CI: 1.21-2.63, P=0.002), Recessive model (OR=1.48, 95% CI: 1.14-1.93, P=0.003). rs760426 A risk allele (OR=1.26, 95% CI: 1.04-1.52, P=0.01); Recessive model (OR=1.33, 95% CI: 1.02-1.73, P=0.03). In addition, rs878081 and rs1800520 SNPs were not allele and genotyped polymorphisms were significantly associated with RA susceptibility. CONCLUSION: The rs2075876 and rs760426 loci of the AIRE gene are associated with increased risk for rheumatoid arthritis among ethnic Han Chinese from ShaanXi. PMID- 27264827 TI - [Association of eight single nucleotide polymorphisms of chromosomes 20 and X with androgenetic alopecia among ethnic Han Chinese from Yunnan]. AB - OBJECTIVE: To assess the association of 8 single nucleotide polymorphisms (SNPs) from chromosomes X and 20 with androgenetic alopecia among ethnic Han population from Yunnan province. METHODS: An eight-SNP co-amplification protocol was developed for the genotyping with a SNaPshot platform. A case-control study was carried out for the 8 SNPs from chromosomes X and 20 in 115 androgenetic alopecia cases and 125 healthy controls. Statistical analysis was conducted with SPSS17.0, Haploview4.2, SHEsis and MDR software. RESULTS: No association was found between the two groups with regard to the 4 SNPs located on the X chromosome. The genotypic frequencies of rs2180439, rs913063 and rs1160312 were significantly different between the two groups (P < 0.05). The frequency of T allele of rs2180439 was significantly higher in the case group (P < 0.05). The frequencies of A alleles of rs913063 and rs1160312 were significantly higher in the case group (P < 0.05). The haplotypes of C-T-C-G, T-C-C-G and T-T-A-A based on rs6137444-rs2180439-rs913063-rs1160312 showed significant difference between the two groups (P <0.05). rs6137444, rs21804393 and rs1160312 have a strong association with androgenetic alopecia. CONCLUSION: The 4 SNPs located on chromosome X were all monomorphic among ethnic Hans from Yunnan. The rs6152, rs16990427, rs1352015, rs1385699 SNPs located on chromosome 20 are associated with androgenetic alopecia in the same population. Individuals with T allele of rs2180439 and A allele of rs913063 and rs1160312 are more likely to develop androgenetic alopecia. PMID- 27264828 TI - [Association of common copy number variations with diseases]. AB - Genomic polymorphisms come in various forms including single nucleotide variations, translocations, insertions and copy number variations (CNVs). As a form of structural variation, the CNVs comprise common and rare forms based on their populational frequencies. Studies have demonstrated that certain CNVs are associated with risks for neuro-developmental diseases, viral infections, chronic inflammations, and cancers. With the development of high-resolution genome typing technologies such as microarrays and whole genome sequencing, the human genomic CNVs map has been continuously improved and refined. In-depth study of CNVs not only can provide comprehensive understanding for their structural variations and genetic evolution, but also provide new insights into genetic factors contributing to such diseases. In this paper, the general characteristics, pathogenesis and detection methods for the CNVs, as well as their association with human diseases are reviewed. PMID- 27264829 TI - [Parkinson's disease and nucleolar stress]. AB - Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized mainly by motor dysfunction resulting in bradykinesia, rigidity, tremor, gait impairment, and postural instability. The classic pathogenic feature of PD is preferential loss of dopaminergic neurons in the substantia nigra. Downregulation of rRNA transcription is one of major mechanisms to maintain cellular homeostasis under stress conditions. Nucleolar stress has emerged as a component of the degenerative process caused by impaired rRNA transcription and altered nucleolar integrity. Recent study has indicated that the response to stress conditions and quality control mechanisms are impaired in PD, and that metabolic stress may be a trigger mechanism for PD. This review aims to present evidence for a role of nucleolar stress in PD and has summarized mechanisms by which nucleolar stress may play a role in the progression of PD. PMID- 27264830 TI - [Not Available]. PMID- 27264832 TI - In the light of recent advances: eosinophil, eosinophilia and idiopathic hypereosinophilic syndrome. PMID- 27264831 TI - Improving training for sensory augmentation using the science of expertise. AB - Sensory substitution and augmentation devices (SSADs) allow users to perceive information about their environment that is usually beyond their sensory capabilities. Despite an extensive history, SSADs are arguably not used to their fullest, both as assistive technology for people with sensory impairment or as research tools in the psychology and neuroscience of sensory perception. Studies of the non-use of other assistive technologies suggest one factor is the balance of benefits gained against the costs incurred. We argue that improving the learning experience would improve this balance, suggest three ways in which it can be improved by leveraging existing cognitive science findings on expertise and skill development, and acknowledge limitations and relevant concerns. We encourage the systematic evaluation of learning programs, and suggest that a more effective learning process for SSADs could reduce the barrier to uptake and allow users to reach higher levels of overall capacity. PMID- 27264833 TI - Amifostine treatment in patients with myelodysplastic syndrome. AB - Myelodysplastic syndrome (MDS) is a clonal disorder that is characterized by peripheral cytopenia and the induction of apoptosis is thought to be partially responsible for pathological haematopoiesis in MDS. Amifostine is a cytoprotective and antioxidant agent, and it may prolong the survival of progenitor cells in MDS by delaying apoptosis. The study has been carried out with 9 MDS cases. Four of them were diagnosed as refractory anemia (MDS-RA), two as refractory anemia with ring sideroblasts (MDS-RARS) and the remaining three as refractory anemia with excess blasts (MDS-RAEB) according to the French-American British (FAB) classification. Amifostine was given in a dose of 400 mg/m2, as an IV infusion administered in 5-6 minutes, three times a week for 4 consecutive weeks. Three of the cases (33.3%), two with MDS RARS and one with MDSRA, showed a significant improvement in the number of total leukocyte, neutrophil and reticulocyte counts and a decrease in the requirement of erithrocyte transfusions. In clinically responsive cases, all hematological parameters returned back to pre-treatment values two weeks after the cessation of therapy. We conclude that Amifostine can be used in a selected group of patients with MDS RA and MDS-RARS. PMID- 27264834 TI - Haematological and biochemical response to treatment of HIV-1 infection with a combination of nevirapine + stavudine + lamivudine in Lagos Nigeria. AB - To evaluate the effect of a combination of nevirapine + stavudine + lamivudine on Haematological and Biochemical values of HIV-1 positive patients in Lagos. Fifty patients who met the enrollment criteria for accelerated clinical trial were studied. Ten millimeters of blood was taken from each patient at first visit for basic haematological and biochemical values. Viral load and CD4 cell counts were also analyzed. All the values were repeated at 12 weeks, and 24 weeks, after patients were placed on drug treatment regimen. All the data were analyzed using Epi-info version 6.4D. The mean erythrocyte sedimentation rate (ESR) results were 53.3 +/- 41.8 mm/1 hr, 48.2 +/- 40.6 mm/1 hr and 28.6 +/- 20.7 mm/1 hr. Haemoglobin (Hb) 123 +/- 15 g/L, 124 +/- 21 g/L and 132 +/- 14 g/L. Packed cell volume 36.8 +/- 4.5%, 37.6 +/- 4.8%, and 40.3 +/- 3.3%. Total white blood cell (WBC) 4.2 +/- 1.0, 5.0 +/- 1.5 and 4.6 +/- 1.0 (baseline, 12 weeks and 24 weeks respectively). Creatinine, 1.2 +/- 0.68 g/L, 1.2 +/- 0.7 g/L and 1.04 +/- 0.3 g/L at (baseline, 12 weeks and 24 weeks respectively). Serum amylase 37.9 +/- 15.1 IU/L, 38 +/- 23.9 IU/L and 24.3 +/- 11.6 IU/L. Triglyceride 95.2 +/- 48.3 IU/L, 92.38 +/- 54.3 IU/L, and 78.0 +/- 35.6 IU/L. Serum bilirubin 0.18 +/- 0.09 MUmol/L, 0.29 +/- 0.28 MUmol/L and 0.33 +/- 0.24 MUmol/L. Alanine transaminase (ALT) 9.9 +/- 3.3 IU/L, 15.1 +/- 9.0 IU/L and 14.1 +/- 9.3 IU/L. Serum aspartate transaminase (AST) 8.2 +/- 6.2 IU/L, 9.4 +/- 5.2 IU/L and 9.1 +/- 6.0 IU/L. On comparison of the results between baseline and 12th week, all parameter were similar except PCV, Hb, serum bilirubin, serum ALT, and total WBC, which were significantly high at 12th week. (p<= 0.05). On comparison of results between 12th week and 24th week all parameters were similar except Hb and PCV (which were significantly higher at 24th week) while ESR, was significantly lower at 24th week (p<= 0.05). It was concluded that nevirapine + stavudine + lamivudine combination results in improved haematological values of HIV/AIDS patients. The effect of the drug combination on biochemical parameter in a short period of 24 weeks may not be much. Clinical response and haematological response alone may be used for patient monitoring in a resource poor setting where CD4 count and viral load analysis is impossible. PMID- 27264835 TI - Microbiologically documented infections following peripheral blood stem cell transplantation: single center experience. AB - This study was performed to assess the incidence of infectious complications in patients undergoing autologous and allogeneic hematopoietic stem cell transplantation (HSCT). The characteristics of microbiologically documented infections in 114 consecutive patients undergoing HSCT (84 autologous, 30 allogeneic) were analyzed. Conditioning and the pre-engraftment period until one month was defined as the early period; the post-engraftment period until one year was defined as the late period. All patients received antibiotic prophylaxis and hematopoietic growth factors during neutropenia. Febrile patients received imipenem-cilastatin or cefepime plus amikacin or ceftazidime plus amikacin. A total of 117 episodes with microbiologically documented infections were seen 90 of 114 patients and 79% of the patients experienced at least one febrile episode during their post-transplant course. Of these episodes, 69 (59%) were in the early period and 48 (41%) were in the late period. In the early period, 38.8% of causative organisms were gram-positive, 51.5% were gramnegative and 7.7% were fungi. The most common pathogens were coagulase-negative Staphylococcus (CoNS) and E. coli in the early period. In the late period, 44.6% of causative organisms were gram-positive, 44.6% were gram-negative and 6.8% were fungi. CoNS and E. coli were also the most commonly isolated agents in this period. Resistance to methicillin was detected in 47.4% of S. aureus and 86.5% of CoNS isolates. The isolation rate was in accordance with previous reports; similar percentages of gram-positive and gram-negative isolates were found in patients undergoing HSCT in both periods. However, a remarkably low rate of viridans streptococci and fungi were observed. The spectrum of pathogens detected in these cases serves as the basis for recommendations on the choice of empiric antimicrobial treatment regimens. Therefore, studies reporting local microbiological findings are necessary. We suggest that local microbiologic surveillance should be known before empiric antimicrobial therapy is started in each institution. PMID- 27264836 TI - Thoracic splenosis. AB - Intrathoracic splenosis is a rare condition that results after rupture of the spleen or diaphragmatic injury. We present herein a case of intrathoracic splenosis of a 48-years-old woman whom splenectomy had been performed 5 years ago after a traffic accident. The patient was operated on with suspicion of malignancy and total resection of the lesion was performed with video-assisted thoracic surgery (VATS). Histopathologic examination confirmed the splenosis diagnosis. Thoracic splenosis should be suspected for the patients with thoracic lesions whom had medical history of thoracoabdominal injury including splenectomy or diaphragmatic injury. PMID- 27264838 TI - Images in Hematology. PMID- 27264837 TI - Calcinosis cutis in a pediatric patient with Burkitt's lymphoma. AB - Calcinosis cutis, an uncommon disorder characterized by hydroxyapatite crystals of calcium phosphate deposited in the skin, has been described infrequently in childhood. Cutaneous calcification may be divided into four major categories: dystrophic, metastatic, idiopathic, and iatrogenic. Here, we report an example of iatrogenic type with a 4-year-old boy who diagnosed with Burkitt's lymphoma, and developed calcinosis cutis secondary to a tumour lysis syndrome with induction chemotherapy. PMID- 27264840 TI - Bidentate forms of beta-triketimines: syntheses, characterization and outstanding performance of enamine-diimine cobalt complexes in isoprene polymerization. AB - New cationic enamine-beta-diimine cobalt complex [LCoBr.THF][BArF] () and its neutral analogue [LCoBr2] () where L = [(2,4,6-Me3-C6H2)NHCMe[double bond, length as m-dash]C{CMe[double bond, length as m-dash](N-2,4,6-Me3(C6H2))}2] and BArF(-) = [{3,5-(CF3)2C6H3}4B](-), were synthesised and then characterized by single crystal X-ray diffraction, MALDI-MS, IR and elemental analysis. These complexes, the first examples reported where putatively tridentate beta-triketimines prefer a bidentate coordination mode, were examined as catalysts for the polymerization of isoprene, activated by diethylaluminium chloride (DEAC) or ethylaluminium sesquichloride (EASC). The weakly coordinating BArF anion in strongly improved activity in comparison to . Both and produced polyisoprene of ca. 80% cis-1,4 and 20% 3,4 enchainment, with trace levels of trans-1,4 and no 1, 2 polymer. A kinetic study for both and demonstrated that the polymerization was first-order in monomer and that approximately 46% and 50% of cobalt formed active centres for and respectively. EASC was the most active of a range of organoaluminium compounds screened for both and . The resulting activities of up to 6 * 10(5) mol isoprene per mol Co per h are the highest yet recorded for catalysts selective for cis-1,4 enchained polyisoprene. PMID- 27264839 TI - Immunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cells. AB - Experimental as well as clinical studies demonstrate that the immune system plays a major role in controlling generation and progression of tumors. The cancer immunoediting theory supports the notion that tumor cell immunogenicity is dynamically shaped by the immune system, as it eliminates immunogenic tumor cells in the early stage of the disease and then edits their antigenicity. The end result is the generation of a tumor cell population able to escape from immune recognition and elimination by tumor infiltrating lymphocytes. Two major mechanisms, which affect the target cells and the effector phase of the immune response, play a crucial role in the editing process. One is represented by the downregulation of tumor antigen (TA) processing and presentation because of abnormalities in the HLA class I antigen processing machinery (APM). The other one is represented by the anergy of effector immune infiltrates in the tumor microenvironment caused by aberrant inhibitory signals triggered by immune checkpoint receptor (ICR) ligands, such as programmed death ligand-1 (PD-L1). In this review, we will focus on tumor immune escape mechanisms caused by defects in HLA class I APM component expression and/or function in different types of cancer, with emphasis on head and neck cancer (HNC). We will also discuss the immunological implications and clinical relevance of these HLA class I APM abnormalities. Finally, we will describe strategies to counteract defective TA presentation with the expectation that they will enhance tumor recognition and elimination by tumor infiltrating effector T cells. PMID- 27264841 TI - Chemoselective modifications for the traceless ligation of thioamide-containing peptides and proteins. AB - Thioamides are single-atom substitutions of canonical amide bonds, and have been proven to be versatile and minimally perturbing probes in protein folding studies. Previously, our group showed that thioamides can be incorporated into proteins by native chemical ligation (NCL) with Cys as a ligation handle. In this study, we report the expansion of this strategy into non-Cys ligation sites, utilizing radical initiated desulfurization to "erase" the side chain thiol after ligation. The reaction exhibited high chemoselectivity against thioamides, which can be further enhanced with thioacetamide as a sacrificial scavenger. As a proof of-concept example, we demonstrated the incorporation of a thioamide probe into a 56 amino acid protein, the B1 domain of Protein G (GB1). Finally, we showed that the method can be extended to beta-thiol amino acid analogs and selenocysteine. PMID- 27264842 TI - Effect of the gel elasticity of model skin matrices on the distance/depth dependent transmission of vibration energy supplied from a cosmetic vibrator. AB - OBJECTIVE: The purpose of this study was to determine how the energies supplied from a cosmetic vibrator are deeply or far transferred into organs and tissues, and how these depths or distances are influenced by tissue elasticity. METHODS: External vibration energy was applied to model skin surfaces through a facial cleansing vibrator, and we measured a distance- and depth-dependent energy that was transferred to model skin matrices. As model skin matrices, we synthesized hard and soft poly(dimethylsiloxane) (PDMS) gels, as well as hydrogels with a modulus of 2.63 MPa, 0.33 MPa and 21 kPa, respectively, mostly representing those of skin and other organs. The transfer of vibration energy was measured either by increasing the separation distances or by increasing the depth from the vibrator. RESULTS: The energies were transmitted deeper into the hard PDMS than into the soft PDMS and hydrogel matrices. This finding implies that the vibration forces influence a larger area of the gel matrices when the gels are more elastic (or rigid). There were no appreciable differences between the soft PDMS and hydrogel matrices. However, the absorbed energies were more concentrated in the area closest to the vibrator with decreasing elasticity of the matrix. Softer materials absorbed most of the supplied energy around the point of the vibrator. In contrast, harder materials scattered the external energy over a broad area. CONCLUSIONS: The current results are the first report in estimating how the external energy is deeply or distantly transferred into a model skins depending on the elastic moduli of the models skins. In doing so, the results would be potentially useful in predicting the health of cells, tissues and organs exposed to various stimuli. PMID- 27264843 TI - Sorafenib treatment in children with relapsed and refractory neuroblastoma: an experience of four cases. AB - Metastatic neuroblastoma is an aggressive malignancy with a poor prognosis. Recent findings have shown that sorafenib decreases cell viability and increases apoptosis in human neuroblastoma cell lines. We report an experience of compassionate use of sorafenib in children with treatment-refractory neuroblastoma. Sorafenib showed transient anti-tumor activity in all four patients without adverse effects. However, progression was observed after a short stabilization phase. While sorafenib showed minimal anti-tumor activity in our patients, it might still be effective in patients with neuroblastoma in an earlier stage. PMID- 27264845 TI - A swelling-suppressed Si/SiOx nanosphere lithium storage material fabricated by graphene envelopment. AB - A swelling-suppressed, Si nanocrystals-embedded SiOx nanospheres lithium storage material was prepared by graphene envelopment. The free void spaces formed between the graphene envelope and Si/SiOx nanospheres effectively accommodated the volume changes of Si/SiOx nanospheres during cycling, which significantly suppresses the swelling behavior and improves the capacity retention up to 200 cycles. PMID- 27264844 TI - Admission inferior vena cava measurements are associated with mortality after hospitalization for acute decompensated heart failure. AB - BACKGROUND: Prognostication of patients hospitalized with acute decompensated heart failure (ADHF) is important to patients, providers, and healthcare systems. Few bedside tools exist to prognosticate patients hospitalized with ADHF. OBJECTIVE: The objective of this study was to assess the relationship between inferior vena cava (IVC) diameter and postdischarge mortality in patients hospitalized with ADHF. DESIGN: Prospective observational study. SETTING: A 247 bed urban teaching hospital in Spain PATIENTS: Ninety-seven patients hospitalized with ADHF. INTERVENTION: None. MEASUREMENTS: The IVC diameter and collapsibility were measured by a hospitalist at the time of admission and discharge. Primary outcome was 90-day all-cause mortality. Secondary outcomes were readmission rates at 90 and 180 days, and 180-day all-cause mortality. Patients were followed for 180 days. RESULTS: Data from 80 patients were analyzed. From admission to discharge, a significant improvement in IVC maximum (IVCmax ) diameter (2.12 vs 1.87 cm; P < 0.001) and IVC collapsibility (25.7% vs 33.1%; P < 0.001) was seen in the total study cohort. During the 90-day follow-up period, 11 patients (13.7%) died. An admission IVCmax diameter >=1.9 cm was associated with a higher mortality rate at 90 days (25.4% vs 3.4%; P = 0.009) and 180 days (29.3% vs 3.4%; P = .003). In a multivariate Cox proportional hazards regression analysis, admission IVCmax diameter was an independent predictor of 90-day mortality (hazard ratio [HR]: 5.88; 95% confidence interval [CI]: 1.21-28.10; P = 0.025) and 90-day readmission (HR: 3.20; 95% CI: 1.24-8.21; P = 0.016). CONCLUSION: In patients hospitalized with acute decompensated heart failure, a dilated IVC by bedside ultrasound at the time of admission is associated with a higher 90-day mortality after hospitalization. Journal of Hospital Medicine 2016;11:778-784. (c) 2016 Society of Hospital Medicine. PMID- 27264846 TI - Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers. AB - Electrospray ion mobility-mass spectrometry (IM-MS) data show that for some small molecules, two (or even more) ions with identical sum formula and mass, but distinct drift times are observed. In spite of showing their own unique and characteristic fragmentation spectra in MS/MS, no configurational or constitutional isomers are found to be present in solution. Instead the observation and separation of such ions appears to be inherent to their gas-phase behaviour during ion mobility experiments. The origin of multiple drift times is thought to be the result of protonation site isomers ('protomers'). Although some important properties of protomers have been highlighted by other studies, correlating the experimental collision cross-sections (CCSs) with calculated values has proven to be a major difficulty. As a model, this study uses the pharmaceutical compound melphalan and a number of related molecules with alternative (gas-phase) protonation sites. Our study combines density functional theory (DFT) calculations with modified MobCal methods (e.g. nitrogen-based Trajectory Method algorithm) for the calculation of theoretical CCS values. Calculated structures can be linked to experimentally observed signals, and a strong correlation is found between the difference of the calculated dipole moments of the protomer pairs and their experimental CCS separation. PMID- 27264847 TI - Cooperative enhancement versus additivity of two-photon-absorption cross sections in linear and branched squaraine superchromophores. AB - The linear and nonlinear optical properties of a series of oligomeric squaraine dyes were investigated by one-photon absorption spectroscopy (1PA) and two-photon absorption (2PA) induced fluorescence spectroscopy. The superchromophores are based on two indolenine squaraine dyes with transoid (SQA) and cisoid configuration (SQB). Using these monomers, linear dimers and trimers as well as star-shaped trimers and hexamers with benzene or triphenylamine cores were synthesised and investigated. The red-shifted and intensified 1PA spectra of all superchromophores could well be explained by exciton coupling theory. In the linear chromophore arrangements we also found superradiance of fluorescence but not in the branched systems. Furthermore, the 2PA showed enhanced cross sections for the linear oligomers but only additivity for the branched systems. This emphasizes that the enhancement of the 2PA cross section in the linear arrangements is probably caused by orbital interactions of higher excited configurations. PMID- 27264849 TI - High-Rate Intercalation without Nanostructuring in Metastable Nb2O5 Bronze Phases. AB - Nanostructuring and nanosizing have been widely employed to increase the rate capability in a variety of energy storage materials. While nanoprocessing is required for many materials, we show here that both the capacity and rate performance of low-temperature bronze-phase TT- and T-polymorphs of Nb2O5 are inherent properties of the bulk crystal structure. Their unique "room-and-pillar" NbO6/NbO7 framework structure provides a stable host for lithium intercalation; bond valence sum mapping exposes the degenerate diffusion pathways in the sites (rooms) surrounding the oxygen pillars of this complex structure. Electrochemical analysis of thick films of micrometer-sized, insulating niobia particles indicates that the capacity of the T-phase, measured over a fixed potential window, is limited only by the Ohmic drop up to at least 60C (12.1 A.g(-1)), while the higher temperature (Wadsley-Roth, crystallographic shear structure) H phase shows high intercalation capacity (>200 mA.h.g(-1)) but only at moderate rates. High-resolution (6/7)Li solid-state nuclear magnetic resonance (NMR) spectroscopy of T-Nb2O5 revealed two distinct spin reservoirs, a small initial rigid population and a majority-component mobile distribution of lithium. Variable-temperature NMR showed lithium dynamics for the majority lithium characterized by very low activation energies of 58(2)-98(1) meV. The fast rate, high density, good gravimetric capacity, excellent capacity retention, and safety features of bulk, insulating Nb2O5 synthesized in a single step at relatively low temperatures suggest that this material not only is structurally and electronically exceptional but merits consideration for a range of further applications. In addition, the realization of high rate performance without nanostructuring in a complex insulating oxide expands the field for battery material exploration beyond conventional strategies and structural motifs. PMID- 27264848 TI - Selective attention in dairy cattle. AB - In a replication of Reynolds (1961), two cows learned to discriminate between compound stimuli in a forced choice procedure where pushing through a one-way gate marked with a red cross (S+) gave access to food. Pushing through a one-way gate marked with a yellow triangle (S-) gave no access to food. To investigate whether shape or colour was controlling behaviour, probe tests varied either the shape or the colour of the stimuli (e.g., a red vs. a yellow cross, and a red cross vs. a red triangle). Results suggested control by colour rather than shape, as the gate marked with the red stimulus was chosen more than the gate marked with the yellow stimulus regardless of stimulus shape, and when two shapes of the same colour (either red or yellow) were presented, cows chose both equally. Further probe tests with painted red, white, and yellow stimuli showed that the cows had learned to avoid yellow rather than to approach red, suggesting discriminative behaviour was controlled by the colour of the negative stimulus and not by either aspect of the positive stimulus. It is not clear why the negative stimulus was more salient, but it may reflect a tendency for cows to learn to avoid farm handling practices which involve mainly negative stimuli. PMID- 27264850 TI - Mental Health Issues and Special Care Patients. AB - Mental illness is a major health issue in the world today, yet often remains misunderstood, unrecognized, and undertreated. Patients suffering from severe psychiatric disorders generally display poor oral health, often as a consequence of both lifestyle and avoidant-type behaviors that become exacerbated by their illness. Individuals with severe mental illness display a greater incidence of oral disease compared with a similar demographic not dealing with these particular disorders. Efforts to enhance the oral health of these vulnerable patients will play a significant role in the overall rebuilding of their self esteem and contribute positively to their journey toward stability and recovery. PMID- 27264851 TI - Tools and Equipment for Managing Special Care Patients Anywhere. AB - This article describes many of the tools and equipment used by dental professionals to successfully treat special care patients in a variety of settings. Such equipment can be used in the dental office, operating room, hospital, surgical center, nursing home, private home, institution, hospice, and even in the field without electricity. Equipment discussed includes seating, laughing gas and sedation systems, body wraps and mouth props, lighting, radiographic exposure and imaging systems, dental isolation devices, and other tools the authors use. PMID- 27264852 TI - Ensuring Maintenance of Oral Hygiene in Persons with Special Needs. AB - Patients with special needs often must rely on inadequately trained caregivers for oral health maintenance. Consequently, full compliance is often not achieved. It is crucial that dentists carefully consider restorative materials and restoration design to maximize durability and facilitate cleansing in these challenging circumstances. This article discusses materials selection, prosthetic design, and oral hygiene techniques for caregivers to ensure longevity and maintenance of oral health in the special needs population. PMID- 27264853 TI - Evidence-based Dentistry and Its Role in Caring for Special Needs Patients. AB - Evidence-based dentistry is a concept ideally suited and applicable to special needs dentistry. As the special needs of patients varies according to the individual, so should the way we evaluate our patient, prescribe a course of treatment, and implement that treatment plan. Future generations of dental students and residents should be trained in these concepts not just for patients with special needs, but also for the general patient population. It is imperative that the dental community not retreat in the face of what many deem to be "difficult" patients with special needs. Knowledge and training can overcome many barriers to treatment. PMID- 27264854 TI - The Dental Needs and Treatment of Patients with Down Syndrome. AB - Down syndrome is a common disorder with many oral conditions and systemic manifestations. Dentists need to take a holistic approach including behavioral, oral, and systemic issues. This review of the literature focuses on oral anomalies, systemic interaction, management, and recommendations. PMID- 27264855 TI - Americans with Disabilities Act: Its Importance in Special Care Dentistry. AB - This article focuses on understanding the Americans with Disabilities Act and developmental disabilities for health care providers in special care dentistry. Essential to this awareness is a comprehension of statutory and regulatory requirements and how state disability acts can be more rigorous in application. Developmental disabilities are re-examined in the context of the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Understanding of intellectual disability, epilepsy, autism spectrum disorder, and cerebral palsy is necessary because the management of oral health considerations for special care patients has become ever more complex and indispensable. PMID- 27264856 TI - Making Treatment of Special Needs Patients an Important Part of Your Growing Dental Practice. AB - Today many young dentists want to find a way to make their practices satisfying in ways other than the financial rewards of dentistry. Some of these practitioners have gained additional training in diagnosis and treatment of medically and physically compromised patients in hospital-based, general practice residency programs. A hospital affiliation can create a unique niche that will allow dentists to differentiate themselves from other dentists. By welcoming those ongoing relationships for patients with special needs, and having the resources and desire to treat them, dentists will achieve greater visibility and a reputation as caring, capable practitioners in their community. PMID- 27264857 TI - Treatment of Orally Handicapped Edentulous Older Adults Using Dental Implants. AB - The oral handicap of complete edentulism is the terminal outcome of a multifactorial process involving biological factors and patient-related factors. Fully edentulous orally handicapped older adults have been neglected because removable acrylic dentures have been the classic therapy for complete edentulism but are only rehabilitative, not therapeutic. Not replacing missing teeth with stable dentures could prevent adequate food intake. Osseointegrated endosseous implants used as a therapeutic adjunct can reduce the problem of long-term bone resorption to less than 0.1 mm per year. Implant-borne prostheses substantially increase the overall health and quality of life of orally handicapped fully edentulous older adults. PMID- 27264858 TI - Communicating with Patients with Special Health Care Needs. AB - People with special health care needs (PSHCN) often have difficulty communicating with providers in health care settings, including dental practices. This difficulty can affect access to care as well as the quality of care received. This article provides practical tips and tools dental professionals can use to facilitate communication for a diverse population of PSHCNs. The article discusses communication needs of patients with communication disorders; augmentative and alternative communication; and communication for patients with intellectual disability, psychiatric conditions; and dental fears. Examples are given of communication breakdowns, and descriptions of how communication challenges can be resolved. PMID- 27264859 TI - Neurologic Diseases in Special Care Patients. AB - Neurologic diseases can have a major impact on functional capacity. Patients with neurologic disease require individualized management considerations depending on the extent of impairment and impact on functional capacity. This article reviews 4 of the more common and significant neurologic diseases (Alzheimer disease, cerebrovascular accident/stroke, multiple sclerosis, and Parkinson disease) that are likely to present to a dental office and provides suggestions on the dental management of patients with these conditions. PMID- 27264860 TI - The Special Needs of Preterm Children - An Oral Health Perspective. AB - Preterm births are defined as those before 37 weeks of gestation. With advances in fertility medicine and neonatal medicine, the numbers of preterm children in the community have significantly increased. Developmental delays and complications among preterm children are well recognized. Much less consideration is given to the dental complications of preterm children. Manifestations include palatal deformations, enamel defects, tooth size variations and tooth shape deformities, malocclusions, and increased risks of early childhood caries and tooth wear. This article explores orodental risks and orodental needs of preterm children and suggests preventive and management strategies for optimizing the oral health of special needs children. PMID- 27264862 TI - Special Care Dentistry. PMID- 27264863 TI - Non-destructive evaluation of bacteria-infected watermelon seeds using visible/near-infrared hyperspectral imaging. AB - BACKGROUND: There is a need to minimize economic damage by sorting infected seeds from healthy seeds before seeding. However, current methods of detecting infected seeds, such as seedling grow-out, enzyme-linked immunosorbent assays, the polymerase chain reaction (PCR) and the real-time PCR have a critical drawbacks in that they are time-consuming, labor-intensive and destructive procedures. The present study aimed to evaluate the potential of visible/near-infrared (Vis/NIR) hyperspectral imaging system for detecting bacteria-infected watermelon seeds. RESULTS: A hyperspectral Vis/NIR reflectance imaging system (spectral region of 400-1000 nm) was constructed to obtain hyperspectral reflectance images for 336 bacteria-infected watermelon seeds, which were then subjected to partial least square discriminant analysis (PLS-DA) and a least-squares support vector machine (LS-SVM) to classify bacteria-infected watermelon seeds from healthy watermelon seeds. The developed system detected bacteria-infected watermelon seeds with an accuracy > 90% (PLS-DA: 91.7%, LS-SVM: 90.5%), suggesting that the Vis/NIR hyperspectral imaging system is effective for quarantining bacteria-infected watermelon seeds. CONCLUSION: The results of the present study show that it is possible to use the Vis/NIR hyperspectral imaging system for detecting bacteria infected watermelon seeds. (c) 2016 Society of Chemical Industry. PMID- 27264864 TI - Heparin centenary - an ever-young life-saving drug. AB - On the centenary of the discovery of heparin, the International Journal of Cardiology agreed to publish a collection of mini reviews that summarize the historical development of this ever-young life-saving drug. The present articles deal not only with the historical milestones, but also with current and future perspectives regarding the development of heparin in terms of its structure, as well as on-going biochemical, biological and clinical research. Attention is focused on recent applications of heparin derivatives to non-anticoagulant or antithrombotic therapies, providing particular emphasis on their inhibitory activities, including their potential as anti-cancer agents. In the Chapter, entitled 'Recent innovations in the structural analysis of heparin', some recent technological advances are described for the problem of monitoring the purity and reproducibility of pharmaceutical heparin. These now permit sensitive detection of non-heparin impurities, as well as the detection of heparin from different animal sources, to be made in pharmaceutical heparin samples. In 'Past, present, and future perspectives of heparin in clinical settings and the role of impaired renal function', the author traces the history of heparin and the development of low molecular weight heparin, highlighting the large number of clinical trials in which it has been involved, and reviewing its efficacy among patients with impaired renal function. In the final chapter, 'Old and new applications of non anticoagulant heparin', the authors survey some of the many non-anticoagulant activities of heparin and its derivatives, including glycol-split heparin, which has demonstrated promising activities in a wide-range of situations. PMID- 27264865 TI - Past, present, and future perspectives of heparins in clinical settings and the role of impaired renal function. AB - Heparin, whose discovery goes back one hundred years, was first detected as a thromboplastin from liver tissue, and its anticoagulant action was only identified later. The procoagulant action of heparin, which was later characterized as an immunologic reaction by binding to platelet-factor IV, presenting as heparin-induced thrombocytopenia, remains as a side effect. For more than 60 years heparin has been the immediate anticoagulant of choice in many clinical indications. Further development of heparins resulted in the production of low-molecular weight heparins and Fondaparinux, which substituted heparin for many indications and has received many more new indications, including administration for non-anticoagulant purposes. This development is still ongoing and has resulted in more than 300 registered clinical trials at the end of 2015. All types of heparins are still investigated in patients with impairment of renal function to improve the safety of treatment. New therapeutic strategies for the prevention and treatment of thromboembolism, as well as of the non-anticoagulant actions of natural and modified types of heparins, are studied intensively. The clinical study designs include treatment with vitamin-K and non-vitamin K oral anticoagulants. Consequently, heparins, low-molecular weight heparins and Fondaparinux play an important role in the human health care system. PMID- 27264866 TI - Old and new applications of non-anticoagulant heparin. AB - The aim of this chapter is to provide an overview of non-anticoagulant effects of heparins and their potential use in new therapeutic applications. Heparin and heparin derivatives have been tested in inflammatory, pulmonary and reproductive diseases, in cardiovascular, nephro- and neuro-tissue protection and repair, but also as agents against angiogenesis, atheroschlerosis, metastasis, protozoa and viruses. Targeting and inhibition of specific mediators involved in the inflammatory process, promoting some of the above mentioned pathologies, are reported along with recent studies of heparin conjugates and oral delivery systems. Some reports from the institute of the authors, such as those devoted to glycol-split heparins are also included. Among the members and derivatives of this class, several are undergoing clinical trials as antimetastatic and antimalarial agents and for the treatment of labour pain and severe hereditary anaemia. Other heparins, whose therapeutic targets are non-anticoagulant such as nephropathies, retinopathies and cystic fibrosis are also under investigation. PMID- 27264867 TI - Recent innovations in the structural analysis of heparin. AB - Heparin, the widely used anticoagulant drug, is unusual among major pharmaceutical agents being neither single chemical entity nor a defined mixture of compounds. Its composition, while conforming to approximate average disaccharide composition or sulfation levels, exhibits heterogeneity and variability depending on the source, as well as its geographical origin. Furthermore, individual polysaccharide chains, whose physico-chemical properties are extremely similar, cannot be separated with current state-of-the-art techniques, presenting a challenge to those interested in the quality control of heparin, in ensuring its provenance and safety, and those with an interest in investigating the relationships between its structure and biological activity. The review consists of two main sections: The first is the Introduction, comprising (i) The History, Occurrence and Use of Heparin and (ii) Approaches to Structure-Activity Relationships. The second section is Improved Techniques for Structural Analysis, comprising; (i) Separation and Identification, (ii) Spectroscopic Methods, (iii) Enzymatic Approaches and (iv) Other Physico-Chemical Approaches. The ~60 references cover recent technological advances in the study of heparin structural analysis, largely since 2010. PMID- 27264868 TI - A Salmonella Toxin Promotes Persister Formation through Acetylation of tRNA. AB - The recalcitrance of many bacterial infections to antibiotic treatment is thought to be due to the presence of persisters that are non-growing, antibiotic insensitive cells. Eventually, persisters resume growth, accounting for relapses of infection. Salmonella is an important pathogen that causes disease through its ability to survive inside macrophages. After macrophage phagocytosis, a significant proportion of the Salmonella population forms non-growing persisters through the action of toxin-antitoxin modules. Here we reveal that one such toxin, TacT, is an acetyltransferase that blocks the primary amine group of amino acids on charged tRNA molecules, thereby inhibiting translation and promoting persister formation. Furthermore, we report the crystal structure of TacT and note unique structural features, including two positively charged surface patches that are essential for toxicity. Finally, we identify a detoxifying mechanism in Salmonella wherein peptidyl-tRNA hydrolase counteracts TacT-dependent growth arrest, explaining how bacterial persisters can resume growth. PMID- 27264869 TI - Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53. AB - The mouse double minute 2 (MDM2) oncoprotein is recognized as a major negative regulator of the p53 tumor suppressor, but growing evidence indicates that its oncogenic activities extend beyond p53. Here, we show that MDM2 is recruited to chromatin independently of p53 to regulate a transcriptional program implicated in amino acid metabolism and redox homeostasis. Identification of MDM2 target genes at the whole-genome level highlights an important role for ATF3/4 transcription factors in tethering MDM2 to chromatin. MDM2 recruitment to chromatin is a tightly regulated process that occurs during oxidative stress and serine/glycine deprivation and is modulated by the pyruvate kinase M2 (PKM2) metabolic enzyme. Depletion of endogenous MDM2 in p53-deficient cells impairs serine/glycine metabolism, the NAD(+)/NADH ratio, and glutathione (GSH) recycling, impacting their redox state and tumorigenic potential. Collectively, our data illustrate a previously unsuspected function of chromatin-bound MDM2 in cancer cell metabolism. PMID- 27264871 TI - Taz1-Shelterin Promotes Facultative Heterochromatin Assembly at Chromosome Internal Sites Containing Late Replication Origins. AB - Facultative heterochromatin regulates gene expression, but its assembly is poorly understood. Previously, we identified facultative heterochromatin islands in the fission yeast genome and found that RNA elimination machinery promotes island assembly at meiotic genes. Here, we report that Taz1, a component of the telomere protection complex Shelterin, is required to assemble heterochromatin islands at regions corresponding to late replication origins that are sites of double-strand break formation during meiosis. The loss of Taz1 or other Shelterin subunits, including Ccq1 that interacts with Clr4/Suv39h, abolishes heterochromatin at late origins and causes derepression of associated genes. Moreover, the late-origin regulator Rif1 affects heterochromatin at Taz1-dependent islands and subtelomeric regions. We explore the connection between facultative heterochromatin and replication control and show that heterochromatin machinery affects replication timing. These analyses reveal the role of Shelterin in facultative heterochromatin assembly at late origins, which has important implications for genome stability and gene regulation. PMID- 27264870 TI - Nek1 Regulates Rad54 to Orchestrate Homologous Recombination and Replication Fork Stability. AB - Never-in-mitosis A-related kinase 1 (Nek1) has established roles in apoptosis and cell cycle regulation. We show that human Nek1 regulates homologous recombination (HR) by phosphorylating Rad54 at Ser572 in late G2 phase. Nek1 deficiency as well as expression of unphosphorylatable Rad54 (Rad54-S572A) cause unresolved Rad51 foci and confer a defect in HR. Phospho-mimic Rad54 (Rad54-S572E), in contrast, promotes HR and rescues the HR defect associated with Nek1 loss. Although expression of phospho-mimic Rad54 is beneficial for HR, it causes Rad51 removal from chromatin and degradation of stalled replication forks in S phase. Thus, G2 specific phosphorylation of Rad54 by Nek1 promotes Rad51 chromatin removal during HR in G2 phase, and its absence in S phase is required for replication fork stability. In summary, Nek1 regulates Rad51 removal to orchestrate HR and replication fork stability. PMID- 27264873 TI - The CUE Domain of Cue1 Aligns Growing Ubiquitin Chains with Ubc7 for Rapid Elongation. AB - Ubiquitin conjugation is an essential process modulating protein function in eukaryotic cells. Surprisingly, little is known about how the progressive assembly of ubiquitin chains is managed by the responsible enzymes. Only recently has ubiquitin binding activity emerged as an important factor in chain formation. The Ubc7 activator Cue1 carries a ubiquitin binding CUE domain that substantially stimulates K48-linked polyubiquitination mediated by Ubc7. Our results from NMR based analysis and in vitro ubiquitination reactions point out that two parameters accelerate ubiquitin chain assembly: the increasing number of CUE binding sites and the position of CUE binding within a growing chain. In particular, interactions with a ubiquitin moiety adjacent to the acceptor ubiquitin facilitate chain elongation. These data indicate a mechanism for ubiquitin binding in which Cue1 positions Ubc7 and the distal acceptor ubiquitin for rapid polyubiquitination. Disrupting this mechanism results in dysfunction of the ERAD pathway by a delayed turnover of substrates. PMID- 27264874 TI - Successful treatment of radiation-induced mucositis with proton pump inhibitor administration: A report of two laryngeal cancer cases. AB - Presently, the relationship between laryngopharyngeal reflux (LPR) and radiation induced mucositis has not been fully explored. In the present study, we report 2 cases of laryngeal cancer in which radiation-induced mucositis ameliorated after proton pump inhibitor (PPI) administration. Case 1 was diagnosed with T1aN0M0 right glottis carcinoma and was treated with radiation therapy. Grade 3 mucositis occurred after administration of 46Gy irradiation. PPI was administered and mucositis ameliorated quickly without cessation of radiation therapy. Case 2 was diagnosed with T2N0M0 supraglottic cancer and was treated with concurrent chemoradiation therapy. Grade 3 mucositis occurred after administration of 44Gy irradiation. PPI was administered and mucositis ameliorated quickly without cessation of chemoradiation therapy. In both cases, a remarkable therapeutic effect of PPI was observed in the perilaryngeal areas including the epiglottic vallecula, arytenoid, and postcricoid area. In both cases, LPR involvement was suspected before the onset of radiation therapy. The two cases presented here, indicated a causal relationship between LPR and radiation-induced mucositis. In cases of severe mucositis in the perilaryngeal area in patients with LPR prior to radiation therapy, PPI administration may be an effective therapeutic option. PMID- 27264872 TI - Tissue-Specific Gene Repositioning by Muscle Nuclear Membrane Proteins Enhances Repression of Critical Developmental Genes during Myogenesis. AB - Whether gene repositioning to the nuclear periphery during differentiation adds another layer of regulation to gene expression remains controversial. Here, we resolve this by manipulating gene positions through targeting the nuclear envelope transmembrane proteins (NETs) that direct their normal repositioning during myogenesis. Combining transcriptomics with high-resolution DamID mapping of nuclear envelope-genome contacts, we show that three muscle-specific NETs, NET39, Tmem38A, and WFS1, direct specific myogenic genes to the nuclear periphery to facilitate their repression. Retargeting a NET39 fragment to nucleoli correspondingly repositioned a target gene, indicating a direct tethering mechanism. Being able to manipulate gene position independently of other changes in differentiation revealed that repositioning contributes 1/3 to 2/3 of a gene's normal repression in myogenesis. Together, these NETs affect 37% of all genes changing expression during myogenesis, and their combined knockdown almost completely blocks myotube formation. This unequivocally demonstrates that NET directed gene repositioning is critical for developmental gene regulation. PMID- 27264875 TI - HIV-associated cystic lesions of the parotid gland. AB - We present two cases of an HIV-associated parotid gland cyst. One case was a 36 year-old HIV infected woman. She was diagnosed with HIV infection and presented with slowly enlarged parotid gland cysts together with elevation of HIV viral RNA copies/mL in her serum. She was performed parotid gland biopsy under the general anesthesia. The histopathologic analysis revealed negative HIV p24-antigen in her parotid gland tissue. The other case was a 43-year-old man found his parotid gland swelling shortly after highly active antiretroviral therapy (HAART). He was diagnosed with HIV infection 2 years previously. He had started HAART several days before. He showed exceeding elevation of IgE in his serum. We treated him with medication using anti-histamic drugs for his cyst. A computed tomography scan revealed a complete response of his parotid gland cyst 4 weeks after the medication. His serum IgE level was decreased to half of the level before the medication. These findings suggested that the parotid gland swelling associated with HIV was due to various factors including immune reconstitution inflammatory syndrome (IRIS). In case such a parotid gland swelling, we could avoid invasive treatments. PMID- 27264876 TI - Corrigendum: Excess aldosterone under normal salt diet induces cardiac hypertrophy and infiltration via oxidative stress. PMID- 27264878 TI - Factors influencing community nursing roles and health service provision in rural areas: a review of literature. AB - AIMS: This review sought to better understand the issues and challenges experienced by community nurses working in rural areas and how these factors shape their role. METHODS: Databases were searched to identify relevant studies, published between 1990 and 2015, that focussed on issues and challenges experienced by rural community nurses. Generic and grey literature relating to the subject was also searched. The search was systematically conducted multiple times to assure accuracy. RESULTS: A total of 14 articles met the inclusion criteria. This critical review identified common issues impacting community nursing and included role definition, organisational change, human resource, workplace and geographic challenges. CONCLUSION: Community nurses are flexible, autonomous, able to adapt care to the service delivery setting, and have a diversity of knowledge and skills. Considerably more research is essential to identify factors that impact rural community nursing practice. In addition, greater advocacy is required to develop the role. PMID- 27264877 TI - The quality of recovery on discharge from hospital, a comparison between patients undergoing hip and knee replacement - a European study. AB - AIMS AND OBJECTIVES: To describe and compare the quality of recovery on discharge from hospital among patients undergoing elective hip or knee replacement. The study will also attempt to identify any predicting factors. BACKGROUND: Arthroplasty is commonly used for an increasing population of patients with osteoarthritis, and the recovery process starts directly after surgery. Today's shorter hospital stay may be a challenge for the patients during the early period of recovery. It is therefore important to identify factors associated with quality of recovery at discharge from hospital. DESIGN: A descriptive, comparative study including 12 hospitals in 5 European countries; Cyprus, Finland, Greece, Iceland and Sweden. METHODS: Consecutively included patients responded on: health-related quality of life, and emotions before surgery and at hospital discharge; quality of recovery, patient satisfaction and fulfilment of knowledge expectations. Related factors and associations were analysed separately for each kind of arthroplasty. In total, 865 patients were included (hip n = 413, knee n = 452). RESULTS: In the dimension of pain, patients undergoing hip replacement had significantly better quality of recovery compared to those undergoing knee replacement. Both patient groups experienced negative emotions before surgery that were related to poorer quality of recovery. Fulfilment of knowledge expectations has a limited effect on quality of recovery. Greater satisfaction with care predicted better quality of recovery. CONCLUSIONS: Negative preoperative emotions were related to poorer quality of recovery. For both kinds of arthroplasty, greater satisfaction with care was associated with better quality of recovery. RELEVANCE TO CLINICAL PRACTICE: The result emphasises the need to detect patients in need of support in their preparation and recovery process, taking into account the perspective of their emotional state. PMID- 27264881 TI - Immunomodulatory effects of temperature and pH of water in an Indian freshwater sponge. AB - Eunapius carteri, a freshwater sponge of India, inhabits the ponds and lakes and experiences variations of temperature and pH of water throughout the year. Sponges bear evolutionary and ecological importance with limited information on their immunological attribute and adaptational resilience in a changing environment. This paper reports temperature and pH specific responses of immune related parameters in sponge maintained in the experimental conditions of laboratory. Innate immunological parameters like phagocytosis and generation of cytotoxic molecules like superoxide anion, nitric oxide and phenoloxidase activity were estimated in E. carteri at different environmentally realistic water temperatures (10, 20, 30 and 40 degrees C) and pH (6.4, 7.4 and 8.4). Phagocytosis and cytotoxicity are established as important immune parameters of invertebrates. Calalase, an antioxidant enzyme and phosphatases are involved in pathogen destruction and are considered as components of innate immunity. Activities of catalase, acid and alkaline phosphatases were estimated in E. carteri at different thermal regimes and pH. Modulation of phagocytic and cytotoxic responses and the activities of catalase and phosphatases at different water temperatures and pH indicated temperature and pH specific immunological status of E. carteri. Present investigation deals with the effects of selected hydrological parameters on the fundamental immune related parameters in sponge indicating its adaptational plasticity. Immunological resilience of this species in the face of variation of water temperature and pH is thought to be a special adaptive feature of sponge, a reported "living fossil". PMID- 27264882 TI - Pre-cooling with intermittent ice ingestion lowers the core temperature in a hot environment as compared with the ingestion of a single bolus. AB - The timing in which ice is ingested may be important for optimizing its success. However, the effects of differences in the timing of ice ingestion has not been studied in resting participants. Therefore, the purpose of this study was to investigate the effects of differences in the timing of ice ingestion on rectal temperature (Tre) and rating of perceptual sensation in a hot environment. Seven males ingested 1.25gkg(-1) of crushed ice (ICE1.25: 0.5 degrees C) or cold water (CON: 4 degrees C) every 5min for 30min, or were given 7.5gkgBM(-1) of crushed ice (ICE7.5) to consume for 30min in a hot environment (35 degrees C, 30% relative humidity). The participants then remained at rest for 1h. As physiological indices, Tre, body mass and urine specific gravity were measured. Rating of thermal sensation was measured at 5-min intervals throughout the experiment. ICE1.25 continued to decrease Tre until approximately 50min, and resulted in a greater reduction in Tre (-0.56+/-0.20 degrees C) than ICE7.5 ( 0.41+/-0.14 degrees C). Tre was reduced from 40 to 75min by ICE1.25, which is a significant reduction in comparison to ICE7.5 (p<.05). Mean RTS with ICE1.25 at 50-65min was significantly lower than that with ICE7.5 (p<.05). These results suggest that pre-cooling with intermittent ice ingestion is a more effective strategy both for lowering the Tre and for the rating of thermal sensation. PMID- 27264883 TI - Differential effect of thermal stress on HSP70 expression, nitric oxide production and cell proliferation among native and crossbred dairy cattle. AB - In a tropical country like India, thermal stress is one of the major factors which significantly affects the productivity of dairy cattle. The present study was aimed to identify the effect of heat and cold stress on cell viability, mitogen stimulation indices, nitric oxide production and HSP70 expression in Sahiwal and Holstein crossbred (Frieswal) population in India. The results indicated that the Sahiwal breed can better withstand the effect of heat and cold stress significantly (P<0.05) when compared to the crossbred cattle due to the higher survivability of the Peripheral Blood Mononuclear Cells (PBMCs) and Phytohemagglutinin (PHA-P) mitogen based stimulation indices. The study also revealed the significant differences (P<0.05) in the level of nitric oxide (uM) production amongst the pre and post thermal stressed samples of Sahiwal and Frieswal crossbred samples. Further, the expression of HSP70 was significantly (P<0.05) higher in Sahiwal compared to Frieswal immediately after heat/cold shock to 6h of recovery as indirect ELISA analysis showed gradual rise in the Hsp70 protein concentration (ng/ml) immediately after heat and cold stress (0h) and reached the peak at 6h of recovery. Western blot and immune fluorescent assay results were also corroborated with the findings of indirect ELISA. In Sahiwal cattle the mRNA expression of HSP70 and its protein concentration were higher (P<0.05) during peak summer (44 degrees C) and winter (10 degrees C) as compared to Frieswal cattle. This investigation supports the earlier information on the higher adaptability of indigenous cattle breeds to hot and humid conditions compared to the crossbreds of temperate cattle breeds. PMID- 27264884 TI - An acute bout of whole body passive hyperthermia increases plasma leptin, but does not alter glucose or insulin responses in obese type 2 diabetics and healthy adults. AB - Acute and chronic hyperthermic treatments in diabetic animal models repeatedly improve insulin sensitivity and glycemic control. Therefore, the purpose of this study was to test the hypothesis that an acute 1h bout of hyperthermic treatment improves glucose, insulin, and leptin responses to an oral glucose challenge (OGTT) in obese type 2 diabetics and healthy humans. Nine obese (45+/-7.1% fat mass) type 2 diabetics (T2DM: 50.1+/-12y, 7.5+/-1.8% HbA1c) absent of insulin therapy and nine similar aged (41.1+/-13.7y) healthy non-obese controls (HC: 33.4+/-7.8% fat mass, P<0.01; 5.3+/-0.4% HbA1c, P<0.01) participated. Using a randomized design, subjects underwent either a whole body passive hyperthermia treatment via head-out hot water immersion (1h resting in 39.4+/-0.4 degrees C water) that increased internal temperature above baseline by ?1.6+/-0.4 degrees C or a control resting condition. Twenty-four hours post treatments, a 75g OGTT was administered to evaluate changes in plasma glucose, insulin, C-peptide, and leptin concentrations. Hyperthermia itself did not alter area under the curve for plasma glucose, insulin, or C-peptide during the OGTT in either group. Fasting absolute and normalized (kg.fat mass) plasma leptin was significantly increased (P<0.01) only after the hyperthermic exposure by 17% in T2DM and 24% in HC groups (P<0.001) when compared to the control condition. These data indicate that an acute hyperthermic treatment does not improve glucose tolerance 24h post treatment in moderate metabolic controlled obese T2DM or HC individuals. PMID- 27264885 TI - Modeling heat loss from the udder of a dairy cow. AB - A mechanistic model that predicts sensible and latent heat fluxes from the udder of a dairy cow was developed. The prediction of the model was spot validated against measured data from the literature, and the result agreed within 7% of the measured value for the same ambient temperature. A dairy cow can lose a significant amount of heat (388W/m(2)) from the udder. This suggests that the udder could be considered as a heat sink. The temperature profile through the udder tissue (core to skin) approached the core temperature for an air temperature >=37 degrees C whereas the profile decreased linearly from the core to skin surface for an air temperature less than 37 degrees C. Sensible heat loss was dominant when ambient air temperature was less than 37.5 degrees C but latent heat loss was greater than sensible heat loss when air temperature was >=37.5 degrees C. The udder could lose a total (sensible + latent) heat flux of 338W/m(2) at an ambient temperature of 35 degrees C and blood-flow rate of 3.2*10(-3)m(3)/(sm(3) tissue). The results of this study suggests that, in time of heat stress, a dairy cow could be cooled by cooling the udder only (e.g., using an evaporative cooling jacket). PMID- 27264886 TI - Effect of multiple stress factors (thermal, nutritional and pregnancy type) on adaptive capability of native ewes under semi-arid environment. AB - This study was conducted to evaluate the effect of multiple stress factors (thermal, nutritional and pregnancy type) on two different native track breeds of ewes as reflected by their adaptive capability under semi-arid environment. The multiple stressor experiment was conducted in twenty-four ewes (12 Santa Ines and 12 Morada Nova ewes). Both heat stress and pregnancy stress was common to all four groups. However, the animals were divided into further two groups within each breed on the basis of nutrition regimen. According the groupings were: Group 1 (Six Santa Ines ewes; heat stress; nutrition at 0.5% of BW; single pregnancy); Group 2 (Six Santa Ines ewes; heat stress; nutrition at 1.5% BW; twin pregnancy); groups Group 3 (Six Morada Nova ewes; heat stress; nutrition at 0.5% of BW; single pregnancy); Group 4 (Six Morada Nova ewes; heat stress; nutrition at 1.5% BW; twin pregnancy). All the animals in the experiment were pregnant. Heat stress was induced by exposing all animals to summer heat stress in outside environment while the nutritional regimen followed was at 0.5% and 1.5% level of body weight (BW) respectively in each breed. The experiment was conducted in a completely randomized design with two breeds, two nutritional treatments and two pregnancy types, 10 repetitions for physiological parameters and six for blood parameters, with repeated measures over time. Physiological parameters (respiratory rate, pulse rate and rectal temperature) were measured with the animals at rest in the morning and afternoon, 0600-0700 and 1300-1400h, respectively, every seven days. Blood samples were collected every 14d for determination of serum glucose, triglycerides, cholesterol, urea and creatinine. We found interaction effect between breed and pregnancy type on respiratory rate and rectal temperature with greater values in Santa Ines ewes than Morada Nova ewes. However, there was no significant fixed effect of pregnancy type and supplementation level on physiological responses of breeds. Environmental factor (period of the day) had influenced the physiological responses of ewes during all gestational period. Santa Ines ewes had greater serum glucose concentration at 105d and 120d of gestation compared to the Morada Nova ewes. Morada Nova ewes had greater concentrations of triglycerides, urea at 120d, 150d and also greater cholesterol at 105d, 135d and 150d of gestation compared with Santa Ines ewes. The present result indicates that thermal condition was most important factor that modified the physiological responses of ewes in a semi-arid tropical environment. PMID- 27264887 TI - Age-related changes of serum mitochondrial uncoupling 1, rumen and rectal temperature in goats. AB - Thermoregulatory processes are induced not only by exposure to cold or heat but also by a variety of physiological situations including age, fasting and food intake that result in changes in body temperature. The aim of the present study was to evaluate the differences in serum mitochondrial uncoupling protein 1 (UCP1), rumen temperature (TRUMEN) and rectal temperature (TRECTAL) values between adult and kids goats. Ten adult male Maltese goats aged 3-5 years old (Group A) and 30 male kids, raised for meat, were enrolled in this study. The kids were equally divided into 3 groups according to their age: Group B included kids aged 3 months, Group C included kids aged 4 months and Group D included kids aged 5 months. Blood samples and measurements of TRUMEN and TRECTAL were obtained from each animal. One-way repeated measures analysis of variance (ANOVA) was applied to evaluate the effect of age on the studied parameters. Statistically significant higher serum UCP1 levels (P<0.001) were found in Group A as compared to Groups B, C and D. Higher TRUMEN values (P<0.001) were found in Group A than in Groups B, C and D, and in Group B than in Groups C and D. Group A showed lower TRECTAL values (P<0.001) than Groups B, C and D. The Pearson's Correlation test was applied to assess significant relationship among studied parameters showing a statistically significant negative correlation between the values of TRECTAL and serum UCP1 in all studied Groups (P<0.001). These results indicate that goats have good control of body temperature suggesting that further details about the thermogenic capacity and the function of UCP1 in kids and adult goats are worth exploring. PMID- 27264888 TI - Altitudinal variation in bumble bee (Bombus) critical thermal limits. AB - Organism critical thermal limits are often tightly linked to current geographic distribution and can therefore help predict future range shifts driven by changing environmental temperatures. Thermal tolerance of diverse organisms often varies predictably with latitude, with upper thermal limits changing little and lower thermal limits decreasing with latitude. Despite similarly steep gradients in environmental temperatures across altitude, few studies have investigated altitudinal variation in critical thermal limits. We estimated critical thermal minimum (CTmin), critical thermal maximum (CTmax) and recovery temperature (Trec) by tracking righting response of three bumble bee species during thermal ramps: Bombus huntii collected from 2180m asl, and Bombus bifarius and Bombus sylvicola collected from 3290m asl in Wyoming, USA. Overall, larger bees could tolerate more extreme temperatures, likely due to a thermal inertia driven lag between core body temperatures and air temperatures. Despite their smaller size, high altitude bumble bees tolerated colder air temperatures: they had ~1 degrees C lower CTmin and recovered from cold exposure at ~3-4 degrees C lower air temperatures. Conversely, low altitude bees tolerated ~5 degrees C hotter air temperatures. These altitudinal differences in thermal tolerance parallel differences in average daily minimum (1.2 degrees C) and maximum (7.5 degrees C) temperatures between these sites. These results provide one of the few measurements of organism thermal tolerance across altitude and the first evidence for geographical differences in tolerance of temperature extremes in heterothermic bumble bees. PMID- 27264889 TI - Dynamics of thermographic skin temperature response during squat exercise at two different speeds. AB - Low intensity resistance training with slow movement and tonic force generation has been shown to create blood flow restriction within muscles that may affect thermoregulation through the skin. We aimed to investigate the influence of two speeds of exercise execution on skin temperature dynamics using infrared thermography. Thirteen active males performed randomly two sessions of squat exercise (normal speed, 1s eccentric/1s concentric phase, 1s; slow speed, 5s eccentric/5s concentric phase, 5s), using ~50% of 1 maximal repetition. Thermal images of ST above muscles quadriceps were recorded at a rate of 0.05Hz before the exercise (to determine basal ST) and for 480s following the initiation of the exercise (to determine the nonsteady-state time course of ST). Results showed that ST changed more slowly during the 5s exercise (p=0.002), whereas the delta (with respect to basal) excursions were similar for the two exercises (p>0.05). In summary, our data provided a detailed nonsteady-state portrait of ST changes following squat exercises executed at two different speeds. These results lay the basis for further investigations entailing the joint use of infrared thermography and Doppler flowmetry to study the events taking place both at the skin and the muscle level during exercises executed at slow speed. PMID- 27264890 TI - The in vitro effect of temperature on motility and antioxidant response of common carp Cyprinus carpio spermatozoa. AB - The effect of temperature on Cyprinus carpio spermatozoa in vitro was investigated with spermatozoa activated at 4, 14, and 24 degrees C. At 30s post activation, motility rate was significantly higher at 4 degrees C compared to 14 and 24 degrees C, whereas highest swimming velocity was observed at 14 degrees C. The thiobarbituric acid-reactive substance (TBARS) content was significantly higher at 14 degrees C and 24 degrees C than at 4 degrees C in motile spermatozoa. No significant differences in catalase and superoxide dismutase activity relative to temperature were observed. This study provides new information regarding effect of temperature on lipid peroxidation intensity and spermatozoon motility parameters in carp. The elevation of TBARS seen at higher temperatures could be due to inadequate capacity of antioxidant enzymes to protect the cell against the detrimental effects of oxidative stress induced by higher temperatures. PMID- 27264892 TI - Artificial selection on chill-coma recovery time in Drosophila melanogaster: Direct and correlated responses to selection. AB - Artificial selection can be used to create populations with extreme phenotypic responses to environmental stressors. When artificial selection is applied to a single component of a stress response, this selection may result in correlated responses in other stress responses, a phenomenon called cross-tolerance, which is ultimately controlled by the genetic correlations among traits. We selected for extreme responses to cold tolerance by selecting for chill-coma recovery time from a single temperate population of Drosophila melanogaster. Chill-coma recovery time is a common metric of low, but non-lethal, cold temperature tolerance. Replicated divergent artificial selection was applied to a genetically variable base population for 31 generations, resulting in two cold resistant, two cold susceptible, and two unselected control lines. To quantify the relationship between selection on chill-coma recovery and other metrics of thermal performance, we also measured survivorship after acute cold exposure, survivorship after chronic cold exposure, survivorship after cold exposure following a pre-treatment period (rapid cold hardening), starvation tolerance, and heat tolerance. We find that chill-coma recovery time is heritable within this population and that there is an asymmetric response to increased and decreased chill-coma recovery time. Surprisingly, we found no cross-tolerances between selection on chill-coma recovery time and the other environmental stress response traits. These results suggest that although artificial selection has dramatically altered chill-coma recovery time, the correlated response to selection on other stress response phenotypes has been negligible. The lack of a correlated response suggests that chill-coma recovery time in these selection lines is likely genetically independent from measures of cold survivorship tested here. PMID- 27264891 TI - Effect of heat stress on performance and expression of selected amino acid and glucose transporters, HSP90, leptin and ghrelin in growing pigs. AB - Exposing animals to high ambient temperature provokes heat stress (HS) that may affect cellular function and reduced productive performance. The effect of chronic exposure (21d) of pigs to high ambient temperature on expression of amino acid (b(0,+)AT, CAT1) and glucose (SGLT1, GLUT4) transporters, ghrelin, leptin and HSP90 was evaluated. Eighteen pigs (32.6kg body weight) were distributed into 3 groups: (1) pigs housed under natural high ambient temperature conditions, and fed ad libitum (HS); (2) pigs housed in an air-conditioned room at 24 degrees C (thermo-neutral) fed ad libitum (TNad); (3) pigs housed as in (2), but pair-fed with the HS pigs (TNpf). Body temperature, respiratory frequency, weight gain, feed intake, and feed conversion ratio were measured. At d-21 pigs were euthanized and samples from stomach, duodenum, jejunum, liver, longissimus and semitendinosus muscles, and white adipose tissue were collected for mRNA analysis. In the HS room ambient temperature fluctuated every day (23.6-37.6 degrees C). Respiratory frequency and body temperature were higher in HS pigs (P<0.001). Weight gain and feed intake of TNad were higher (P<0.001) than TNpf and HS; gain: feed ratio was not affected by ambient temperature. Expression of HSP90 was higher in duodenum and longissimus (P<=0.038) of HS compared to TNpf. Expression of ghrelin, leptin and b(0,+)AT were not affected by ambient temperature (P>0.050). CAT1 expression in liver was higher (P=0.050) but in longissimus was lower (P=0.017) in HS than in TNpf pigs. Expression of SGLT1 was higher (P=0.045) in duodenum of HS than in TNpf but it was not different in jejunum (P=0.545); GLUT4 tended to be higher in liver and semitendinosus of HS pigs (P=0.063). In conclusion, feed intake remains low whereas respiratory frequency and body temperature remain higher; and expression of HSP90, CAT1, SGLT1 and GLUT4 increases in some tissues in pigs under chronic HS conditions. PMID- 27264893 TI - Physiological responses to changes in relative humidity under thermally neutral, warm and hot conditions. AB - Four hypothetical thermophysiological responses to changes in relative humidity (Rh) under thermally neutral, warm, and hot conditions were proposed for a person at rest. Under thermally neutral and warm conditions, the first hypothetical response to an increase in Rh was a decrease in mean skin temperature (T-sk) due to increase in mean evaporation rate (E-sk), and the second hypothetical response to a decrease in Rh was a decrease, an increase, or no change in T-sk, depending on changes in the E-sk. Under hot conditions, the third hypothetical response to an increase in the Rh was an increase in T-sk or decrease in T-sk upon decrease in the Rh due to changes in E-sk, and the forth hypothetical response to an increase in Rh was an increase in T-sk due to increase in the peripheral blood flow rate (SkBF). To test these hypotheses, the T-sk and E-sk of four young male volunteers were measured at 28 degrees C, 30 degrees C, or 32 degrees C while the Rh was maintained at 40% or 80% Rh for 60min after 20min exposure at 60% Rh (control condition). In a second experiment, the T-sk, E-sk, and SkBF of five young male volunteers were measured at 34 degrees C-40% Rh or 36 degrees C-40% Rh, or 34 degrees C-70% Rh or 36 degrees C-70% Rh for 60min after 20min exposure at 28 degrees C-60% Rh (control condition). The first hypothesis was partly supported by the findings that the T-sk was lower than the control values at 28 degrees C-80% Rh and the E-sk was higher than the control values at 80% Rh at any tested temperature. The second hypothesis was partly supported by the findings that the T-sk was lower than the control values at 28 degrees C-40% Rh, and there were small changes in both T-sk and E-sk at 30 degrees C-40% Rh. The third and fourth hypotheses were supported by the findings that the T-sk at 36 degrees C 70% Rh was significantly higher (p<0.01) than at 36 degrees C-40% Rh, the E-sk was significantly higher (p<0.01) at 70% Rh than at 40% Rh, and SkBF was positively correlated with T-sk. PMID- 27264894 TI - Analysis of behaviour patterns and thermal responses to a hot-arid climate in rural China. AB - Climate can greatly affect building design, life style and thermal perception for all groups of people; however, this phenomenon has not yet been rigorously evaluated in China's hot-arid climate. The aim of this paper is to present the results of a thermal comfort survey by evaluating the influence of the hot-arid climate upon the behavioural patterns and thermal comfort responses of 160 residents in 65 traditional vernacular houses in Turfan, China, in 2011. In this survey, there were 206 sets of effective data, and the features of the traditional residential buildings and the human behaviour patterns in Turfan were described and analysed. The results showed that the diversified courtyards and shade spaces were the most obvious features of traditional houses in Turfan. People here typically spend most of their time in one of two spaces for eating, resting, and entertaining. It was found that the preferred temperature was 26.5 degrees C. The preferred air velocity occurred at 0.62m/s. A suitable air velocity range of 0.15-1.24m/s was suggested in Turfan. Moreover, the neutral temperature of the local people was 30.1 degrees C (tg or to). The upper limits of the 80% acceptable zone by using the direct and indirect acceptability method were 32.7 and 33.8 degrees C, respectively. The neutral temperature and upper limit of the acceptable zone in Turfan were higher than those of the adaptive standards. Attention should be paid to the role of thermal comfort in influencing building design by using simple passive cooling strategies. The above results are believed to be potentially valuable for the design and evaluation of residential buildings located in hot-arid climate. PMID- 27264895 TI - Editorial. PMID- 27264896 TI - Yesterday, today, and tomorrow: A brief history of the wrist. PMID- 27264897 TI - A structured literature synthesis of wrist outcome measures: An evidence-based approach to determine use among common wrist diagnoses. AB - STUDY DESIGN: Structured literature synthesis. INTRODUCTION: Hand therapists and researchers have numerous options when selecting outcome measures for patients with wrist pathologies. An evidence-based approach to determining which measures are used most often can inform choices. PURPOSE OF THE STUDY: To describe how frequently outcome measures are used in recent randomized controlled trials of patients with wrist diagnoses. Identifying assessment design and related International Classification of Functioning, Disability and Health (ICF) domains provides additional consideration for selection. METHODS: Systematic PubMed and Cumulative Index to Nursing and Allied Health Literature searches for the time frame between January 2005 and March 2015 captured measures used in randomized controlled trials researching wrist-specific fractures, ligament injuries, nerve injuries, arthritis/arthroplasty, or stress injuries/wrist pain. RESULTS: Three most frequent measures used within each diagnostic category are detailed with assessment design described and ICF domain identified. Across diagnoses, grip/pinch strength and Disabilities of Arm, Shoulder and Hand were the most frequently used physical and patient-reported outcome measures, respectively. The Jebsen-Taylor Hand Function Test was the most frequently used performance measure. DISCUSSION AND CONCLUSIONS: Consideration of the evidence, ICF domains, wrist diagnoses, and assessment design can help hand therapists select the measure most appropriate for use. LEVEL OF EVIDENCE: 2a. PMID- 27264898 TI - The ulnar side of the wrist: Clinically relevant anatomy and biomechanics. AB - BACKGROUND: In the hectic environment of a hand therapy clinic, the opportunity to carefully consider the relationships among pathology, pathomechanics, surgical repair techniques, tissue healing, postoperative management, and rehabilitation program development and progression is limited. Clinicians often default to seeking a protocol, a recipe to follow. OBJECTIVES: Using the ulnar side of the wrist as an example, relevant anatomy and biomechanics are directly related to several commonly seen pathologies, including fractures, ligament injuries, and instability. CONCLUSION: Armed with knowledge of anatomy, biomechanics, and surgical procedures, the need for a protocol disappears. Each patient can be individually managed according to his or her unique set of variables and responses to injury, repair, healing, and recovery of function. PMID- 27264899 TI - Epidemiology of distal radius fractures and factors predicting risk and prognosis. AB - STUDY DESIGN: Literature Review. INTRODUCTION: For optimal Distal Radius Fracture (DRF) rehabilitation and fracture prevention, it is important to understand the epidemiology and factors predictive of injury, chronic pain, chronic disability, and subsequent fracture. PURPOSE: To summarize the literature reporting on DRF epidemiology, risk factors, and prognostic factors. METHODS: Literature synthesis. RESULTS: Although incidence varies globally, DRFs are common across the lifespan and appear to be on the rise. Risk of DRF is determined by personal factors (age, sex/gender, lifestyle, health condition) and environmental factors (population density, climate). For example, age and sex influence risk such that DRF is most common in boys/young men and older women. The most common causes of DRF in the pediatric and young adult age groups include playing/sporting activities and motor vehicle accidents. In contrast, the most common mechanism of injury in older adults is a low-energy trauma because of a fall from a standing height. Poorer health outcomes are associated with older age, being female, poor bone healing (or having an associated fracture of the ulnar styloid), having a compensated injury, and a lower socioeconomic status. CONCLUSIONS: Risk stratification according to predictors of chronic pain and disability enable therapists to identify those patients who will benefit from advocacy for more comprehensive assessment, targeted interventions, and tailored educational strategies. The unique opportunity for secondary prevention of osteoporotic fracture after DRF has yet to be realized by treating therapists in the orthopedic community. LEVEL OF EVIDENCE: V. PMID- 27264900 TI - Rehabilitation for scapholunate injury: Application of scientific and clinical evidence to practice. AB - In this article, the development of a rehabilitation approach is describe using scapholunate injury as a model. We demonstrate how scientific and clinical evidence is applied to a treatment paradigm and modified based on emerging evidence. Role of the scapholunate interosseous ligament within the pathomechanics of the carpus, along with the progression of pathology, and specific rehabilitation algorithms tailored to the stage of injury. We review the recent and current evidence on the kinematics of wrist motion during functional activity, role of the muscles in providing dynamic stability of the carpus, and basic science of proprioception. Key relevant findings in each of these inter related areas are highlighted to demonstrate how together they form the basis for current wrist rehabilitation. Finally, we make recommendations for future research to further test the efficacy of these approaches in improving functional outcomes. PMID- 27264901 TI - Role of muscles in the stabilization of ligament-deficient wrists. AB - This article reviews the results of a series of cadaver investigations aimed at clarifying the role of muscles in the stabilization of ligament-deficient wrists. According to these studies, isometric contraction of some forearm muscles induces midcarpal (MC) supination (ie, the abductor pollicis longus, extensor carpi radialis longus, and flexor carpi ulnaris), whereas other muscles induce MC pronation (ie, the extensor carpi ulnaris). Because MC supination implies tightening of the volar scaphoid-distal row ligaments, the MC supination muscles are likely to prevent scaphoid collapse of wrists with scapholunate ligament insufficiency. MC pronator muscles, by contrast, would be beneficial in stabilizing wrists with ulnar-sided ligament deficiencies owing to their ability to tighten the triquetrum-distal row ligaments. Should these laboratory findings be validated by additional clinical research, proprioceptive reeducation of selected muscles could become an important tool for the treatment of dynamic carpal instabilities. PMID- 27264902 TI - Scaphoid tuberosity excursion is minimized during a dart-throwing motion: A biomechanical study. AB - PURPOSE: The purpose of this study was to determine whether the excursion of the scaphoid tuberosity and therefore scaphoid motion is minimized during a dart throwing motion. METHODS: Scaphoid tuberosity excursion was studied as an indicator of scaphoid motion in 29 cadaver wrists as they were moved through wrist flexion-extension, radioulnar deviation, and a dart-throwing motion. RESULTS: Study results demonstrate that excursion was significantly less during the dart-throwing motion than during either wrist flexion-extension or radioulnar deviation. CONCLUSION: If the goal of early wrist motion after carpal ligament or distal radius injury and reconstruction is to minimize loading of the healing structures, a wrist motion in which scaphoid motion is minimal should reduce length changes in associated ligamentous structures. Therefore, during rehabilitation, if a patient uses a dart-throwing motion that minimizes his or her scaphoid tuberosity excursion, there should be minimal changes in ligament loading while still allowing wrist motion. STUDY DESIGN: Bench research, biomechanics, and cross-sectional. LEVEL OF EVIDENCE: Not applicable. The study was laboratory based. PMID- 27264903 TI - Proprioception retraining for a patient with chronic wrist pain secondary to ligament injury with no structural instability. AB - STUDY DESIGN: Case report. INTRODUCTION: Previously published studies demonstrate the importance of the sensory innervation of the carpal ligaments and the implication for the sensorimotor control of the wrist. In addition, this case considers key rehabilitation concepts to include the dart-throwing motion and the stabilizing effect of the forearm muscles. PURPOSE OF THE STUDY: To describe the rehabilitation program for a patient with chronic wrist pain, diagnosed with a partial tear of the dorsal intercarpal ligament and a sprain of the scapholunate ligament of the right wrist. METHODS: The patient participated in a staged treatment plan over a 3-month period (20 sessions), which began with a focus on proprioceptive awareness and joint position sense retraining. The treatment progressed to strengthening of specific muscles to enhance stability of the wrist joint. The patient completed the Quick Disabilities of the Arm, Shoulder and Hand and the patient-rated wrist evaluation on initial evaluation, re-evaluation at ninth session, and discharge at 20th session. RESULTS: Raw scores in the Quick Disabilities of the Arm, Shoulder and Hand and the patient-rated wrist evaluation improved from 33 and 61.5 on initial evaluation to 18 and 17.5 on discharge, respectively. CONCLUSIONS: Sensorimotor techniques including proprioceptive retraining may improve pain, neuromuscular control, and functional outcomes in patients with chronic wrist pain due to ligament injury. The effectiveness of proprioceptive retraining needs to be evaluated in a well-designed randomized controlled trial recruiting this patient population. LEVEL OF EVIDENCE: 5. PMID- 27264904 TI - Early controlled mobilization using dart-throwing motion with a twist for the conservative management of an intra-articular distal radius fracture and scapholunate ligament injury: A case report. AB - This case describes an early controlled mobilization (ECM) approach that uses dart-throwing motion (DTM) with a twist orthoses as an alternative to immobilization for conservative management of a minimally displaced and intra articular distal radius styloid fracture with an associated scapholunate ligament injury in a 47-year-old female health care administrator (JP). Pain-free active DTM began at day 10 (5 times/d) with a dynamic DTM with a twist orthosis worn during the day from weeks 3 to 6. At 6 weeks, JP had pain-free functional mobility and strength with minimal limitation in household and occupational activities, returning to her normal sporting activities by 3 months. ECM led to rapid return of normal functioning in the short term with no apparent impact on intermediate outcomes at 8 months. This case allows hand therapists to consider a similar ECM approach for the management of similar injuries in their patients. LEVEL OF EVIDENCE: Level 5 and case report. PMID- 27264905 TI - Dart-throwing motion with a twist orthoses: Design, fabrication, and clinical tips. PMID- 27264906 TI - Taping techniques for the wrist. PMID- 27264907 TI - Mitochondrial respiratory chain complex IV deficiency complicated with chronic intestinal pseudo-obstruction in a neonate. AB - A female infant born at 36 weeks gestational age with birthweight 2135 g, and who developed respiratory disorder, hyperlactacidemia and hypertrophic cardiomyopathy after birth, was admitted to hospital at 3 days of age. After admission, bilious emesis, abdominal distention, and passage disorder of the gastrointestinal tract were resistant to various drugs. Exploratory laparotomy was performed at 93 days of age, but no organic lesions were identified and normal Meissner/Auerbach nerve plexus was confirmed, which led to a clinical diagnosis of chronic intestinal pseudo-obstruction (CIPO). She was diagnosed with mitochondrial respiratory chain complex IV deficiency on histopathology of the abdominal rectus muscle and enzyme activity measurement. This is the first report of a neonate with mitochondrial respiratory chain complex deficiency with intractable CIPO. CIPO can occur in neonates with mitochondrial respiratory chain disorder, necessitating differential diagnosis from Hirschsprung disease. PMID- 27264909 TI - Hypohidrotic ectodermal dysplasia: A report of two cases. PMID- 27264908 TI - IVA cloning: A single-tube universal cloning system exploiting bacterial In Vivo Assembly. AB - In vivo homologous recombination holds the potential for optimal molecular cloning, however, current strategies require specialised bacterial strains or laborious protocols. Here, we exploit a recA-independent recombination pathway, present in widespread laboratory E.coli strains, to develop IVA (In Vivo Assembly) cloning. This system eliminates the need for enzymatic assembly and reduces all molecular cloning procedures to a single-tube, single-step PCR, performed in <2 hours from setup to transformation. Unlike other methods, IVA is a complete system, and offers significant advantages over alternative methods for all cloning procedures (insertions, deletions, site-directed mutagenesis and sub cloning). Significantly, IVA allows unprecedented simplification of complex cloning procedures: five simultaneous modifications of any kind, multi-fragment assembly and library construction are performed in approximately half the time of current protocols, still in a single-step fashion. This system is efficient, seamless and sequence-independent, and requires no special kits, enzymes or proprietary bacteria, which will allow its immediate adoption by the academic and industrial molecular biology community. PMID- 27264911 TI - Pseudogracilibacillus marinus sp. nov., isolated from a biofilm formed in coastal seawater. AB - A Gram-staining-positive, aerobic, motile, rod-shaped (0.4-0.5*2.0-4.0 um), endospore-forming bacterium, designated strain NIOT.bflm.S4T, was isolated from biofilm formed on high-density polyethylene test coupons in coastal seawater. The strain required seawater for growth. It grew with 1.0-8.0 % (w/v) NaCl, at 4-45 degrees C and at pH 6.5-9.0, with optimum growth with 4.0-5.0 % (w/v) NaCl, at 30 degrees C and at pH 7.0-8.0. Phylogenetic analyses based on 16S rRNA and partial dnaK gene sequences showed that strain NIOT.bflm.S4T formed a phylogenetic lineage with Pseudogracilibacillus auburnensis P-207T, the only known species of the genus Pseudogracilibacillusand shared sequence identities of 96.9 and 83 %, respectively, with this strain. The identities of 16S rRNA and partial dnaK gene sequences with members of other related genera such as Gracilibacillus, Paraliobacillus, Ornithinibacillus, Oceanobacillus, Virgibacillus and Lentibacillus were <=95 and <=78 %, respectively. The DNA G+C content of strain NIOT.bflm.S4T was 39.1 mol%. MK-7 was found as the sole isoprenoid quinone. The major polar lipids of strain NIOT.bflm.S4T were diphosphatidylglycerol, phosphatidylethanolamine and an unknown lipid. The diagnostic diamino acid of the cell-wall peptidoglycan was meso-diaminopimelic acid. Major cellular fatty acids were anteiso-C15 : 0 (27.9 %), anteiso-C17 : 0 (18.6 %), C12 : 0 (8.7 %) and iso C15 : 0 (6.6 %). On the basis of phenotypic, phylogenetic and chemotaxonomic results, we propose that the isolate represents a novel species of the genus Pseudogracilibacillus, for which the name Pseudogracilibacillus marinus sp. nov. is proposed. The type strain is NIOT.bflm.S4T (=KACC 18456T=MTCC 12376T=TBRC 5831T). PMID- 27264910 TI - Intracellular disulfide reduction by phosphine-borane complexes: Mechanism of action for neuroprotection. AB - Phosphine-borane complexes are novel cell-permeable drugs that protect neurons from axonal injury in vitro and in vivo. These drugs activate the extracellular signal-regulated kinases 1/2 (ERK1/2) cell survival pathway and are therefore neuroprotective, but do not scavenge superoxide. In order to understand the interaction between superoxide signaling of neuronal death and the action of phosphine-borane complexes, their biochemical activity in cell-free and in vitro assays was studied by electron paramagnetic resonance (EPR) spectrometry and using an intracellular dithiol reporter that becomes fluorescent when its disulfide bond is cleaved. These studies demonstrated that bis(3-propionic acid methyl ester) phenylphosphine-borane complex (PB1) and (3-propionic acid methyl ester) diphenylphosphine-borane complex (PB2) are potent intracellular disulfide reducing agents which are cell permeable. EPR and pharmacological studies demonstrated reducing activity but not scavenging of superoxide. Given that phosphine-borane complexes reduce cell injury from mitochondrial superoxide generation but do not scavenge superoxide, this implies a mechanism where an intracellular superoxide burst induces downstream formation of protein disulfides. The redox-dependent cleavage of the disulfides is therefore a novel mechanism of neuroprotection. PMID- 27264912 TI - Women Veterans' Treatment Preferences for Disordered Eating. AB - OBJECTIVE: Disordered eating, which includes subclinical and clinical maladaptive eating behaviors, is common among women, including those served by the Veterans Health Administration (VA). We used qualitative methods to determine whether and how women veterans want to receive treatment for disordered eating. METHOD: Women veterans participated in one of seven focus groups/interviews and completed in person demographic and psychological questionnaires. We used thematic analysis of focus groups/interviews to understand preferences for disordered eating treatment. RESULTS: Participants (n = 20) were mostly women of color (55%); mean age was 48 (SD = 15) and 65% had significant psychological symptoms. Few participants described being assessed for disordered eating, but all thought VA should provide treatment for disordered eating. Through thematic analysis, we identified six preferences: 1) treatment for disordered eating should be provided in groups, 2) treatment for disordered eating should provide concrete skills to facilitate the transition out of structured military environments, 3) treatment for disordered eating should address the relationship between eating and mental health, 4) disordered eating can be treated with mindfulness and cognitive behavioral therapy, 5) disordered eating treatment providers should be experienced and take an interactive approach to care, but can come from diverse disciplines, and 6) referrals to treatment for disordered eating should be open ended, occur early, and allow for ongoing, flexible access to treatment. CONCLUSIONS: Women veterans are interested in treatment for disordered eating. Preferred treatments align with existing treatments, could be offered in conjunction with weight loss or primary care services, and should provide social support and interactive learning. PMID- 27264913 TI - Experiences of Advanced Practitioners with Inserting the Copper Intrauterine Device as Emergency Contraception. AB - INTRODUCTION: The copper intrauterine device (IUD) is the most effective method of emergency contraception (EC) available for use after unprotected intercourse. Family planning clinics, commonly staffed by advanced practice clinicians, fulfill a significant role in health care and contraceptive service delivery for women in the United States. There are limited data assessing the perspectives and experiences of these providers in using the copper IUD as EC in these settings. METHODS: Semistructured individual interviews were conducted with 12 advanced practice clinicians with experience inserting the copper IUD. A phenomenological approach was used to frame the study and analysis. A modified version of the Van Kaam method of analysis was used to analyze the data from interview transcripts. RESULTS: Participants reported feelings of responsibility to support long-acting and highly effective methods of contraception. Patients' abilities to provide an accurate history of the last instance of unprotected intercourse in relation to their menstrual cycles and fear of painful insertions influenced participants' willingness to offer the copper IUD. This included provider concerns about causing uterine perforation prompting discontinuation of IUD insertion attempts. The participants perceived patients as having little knowledge about the copper IUD in general and as not being committed to using the copper IUD long term. CONCLUSIONS: Numerous factors influenced advanced practice clinicians' decisions to present the copper IUD as a method of EC. Promoting support and sharing practitioner experiences with inserting the copper IUD as EC may increase practitioner comfort with the copper IUD as EC. PMID- 27264915 TI - Medication Palatability Affects Physician Prescribing Preferences for Common Pediatric Conditions. AB - OBJECTIVES: The objective of this study was to determine if physicians would alter their prescribing preferences after sampling liquid formulations of medications for common pediatric diagnoses. METHODS: This was a prospective interventional before/after study conducted at an academic medical center in the United States. The participants of interest included emergency, family medicine, and pediatric physicians. Participants initially completed a brief survey for their primary oral liquid medication of choice for the treatment of selected disease states. These included otitis media, sinusitis, cellulitis, asthma, colitis, and pneumonia. Participants were asked to choose one of the medication options for each disease and then were given all medications to sample for a taste test. The prescribing preference survey was then repeated. The primary outcome was change in prescribing. McNemar's test was used to evaluate change in proportion of medications chosen before and after taste testing. RESULTS: There were 101 physicians who participated in the study. There were three conditions for which participants changed their prescribing preferences significantly. These were otitis media (change from amoxicillin to cefdinir, difference = 13.2%, 95% confidence interval [CI] = 5.5% to 21.0%), asthma exacerbation (change from dexamethasone or prednisone to prednisolone, 28%, 95% CI = 15.9% to 40.1%), and pneumonia (change from azithromycin to amoxicillin, 16.0%, 95% CI = 6.4% to 25.6%). There was no significant change with respect to the other scenarios. CONCLUSIONS: Physicians showed preferences for certain pediatric medications based on taste and showed significant changes in prescribing preferences for some common pediatric diagnoses after tasting different medications for these conditions. PMID- 27264914 TI - Automated Breast Ultrasound: Dual-Sided Compared with Single-Sided Imaging. AB - The design and performance of a mammographically configured, dual-sided, automated breast ultrasound (ABUS) 3-D imaging system are described. Dual-sided imaging (superior and inferior) is compared with single-sided imaging to aid decisions on clinical implementation of the more complex, but potentially higher quality dual-sided imaging. Marked improvement in image quality and coverage of the breast is obtained in dual-sided ultrasound over single-sided ultrasound. Among hypo-echoic masses imaged, there are increases in the mean contrast-to noise ratio of 57% and 79%, respectively, for spliced dual-sided versus superior or inferior single-sided imaging. The fractional breast volume coverage, defined as the percentage volume in the transducer field of view that is imaged with clinically acceptable quality, is improved from 59% in both superior and inferior single-sided imaging to 89% in dual-sided imaging. Applying acoustic coupling to the breast requires more effort or sophisticated methods in dual-sided imaging than in single-sided imaging. PMID- 27264916 TI - Silica ecosystem for synergistic biotransformation. AB - Synergistical bacterial species can perform more varied and complex transformations of chemical substances than either species alone, but this is rarely used commercially because of technical difficulties in maintaining mixed cultures. Typical problems with mixed cultures on scale are unrestrained growth of one bacterium, which leads to suboptimal population ratios, and lack of control over bacterial spatial distribution, which leads to inefficient substrate transport. To address these issues, we designed and produced a synthetic ecosystem by co-encapsulation in a silica gel matrix, which enabled precise control of the microbial populations and their microenvironment. As a case study, two greatly different microorganisms: Pseudomonas sp. NCIB 9816 and Synechococcus elongatus PCC 7942 were encapsulated. NCIB 9816 can aerobically biotransform over 100 aromatic hydrocarbons, a feat useful for synthesis of higher value commodity chemicals or environmental remediation. In our system, NCIB 9816 was used for biotransformation of naphthalene (a model substrate) into CO2 and the cyanobacterium PCC 7942 was used to provide the necessary oxygen for the biotransformation reactions via photosynthesis. A mathematical model was constructed to determine the critical cell density parameter to maximize oxygen production, and was then used to maximize the biotransformation rate of the system. PMID- 27264917 TI - Therapeutic apheresis in hematopoietic cell transplantation. AB - With the introduction of hematopoietic stem cell transplant (HSCT), transplant associated problems like graft-versus-host disease (GVHD) and transplant associated microangiopathy (TAM) have occurred. In addition, approximately 40% of allogeneic HSCTs are performed across the ABO blood group barrier, bearing the risk for immunohematological complications like severe hemolysis and pure red cell aplasia (PRCA). All these problems can potentially require therapeutic apheresis. In this review, we address recent developments in therapeutic apheresis for patients undergoing allogeneic HSCT for prevention or treatment of hemolysis in minor ABO-incompatible transplantation, treatment of PRCA after major ABO-incompatible transplantation, and treatment of TAM and GVHD. PMID- 27264918 TI - Optimization of transfection of green fluorescent protein in pursuing mesenchymal stem cells in vivo. AB - OBJECTIVE: Green Fluorescent Protein (GFP) has been used as a marker of gene expression and a single cell marker in living organisms in cell biology studies. The important areas that GFP is used are expression levels of different genes in different organisms by inserting GFP in these genes and as a marker in living cells. In this study, we tried to optimize transfection of mesenchymal stem cells, (MSCs) used for regeneration of damaged tissues in animals, by GFP containing plasmid vector by which MSCs can be followed in vivo. METHODS: To this aim, phM-GFP plasmid vector carrying GFP gene and effectene transfection reagent were used. RESULTS: The data revealed that twice transfection of MSCs resulted in higher expression of GFP for longer times as compared to once transfected MSCs. On the other hand, leaving the chemical transfection agents in the medium induced apoptosis after a while. CONCLUSION: As a conclusion we suggest the transfection of MSCs twice with 48 hours interval and removal of transfection agents after 8 hours which removed toxic and apoptotic effects of the chemicals. PMID- 27264919 TI - Seroprevalence of hepatitis and human immuno-deficiency virus in multitransfused patients from a pediatric hematology clinic. AB - OBJECTIVE: Transfusion transmitted hepatitis has been a severe problem in Turkey in pediatric cancer patients and in chronic congenital anemia. The aim of the present study was to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency virus infections in these patients in a University Hospital. METHODS: Multi-transfused 66 children (59 acute leukemia, 6 thalassemia major, 1 severe hereditary spherocytosis) diagnosed and followed-up between May, 2000 and December, 2006 were evaluated. Screening of all the patients for HbsAg, anti-HBs, anti-HBc, anti-HCV and anti-HIV was performed at presentation and during the last follow-up. Serologic studies of leukemic patients were also repeated at the end of the chemotherapy. Hepatitis B vaccination was administered to unvaccinated patients with anemia. All blood products were provided by Blood Bank of the Center. RESULTS: No patient was found HBsAg, anti-HCV or anti-HIV positive at diagnosis and at the end of the therapy. There was history of hepatitis B vaccination in only 42% of the patients at diagnosis due to administration of this vaccine to newborns since 1998. At the beginning of the study, 45 % (n=27) of the leukemic patients were immune for hepatitis B, but after completion of the intensive chemotherapy seropositivity persisted in only 28.8 % (n=17). CONCLUSION: Transmission of these viruses is no longer a real problem even in multitransfused immunosuppressed children in Pediatric Hematology Units as a result of the improvements in screening of voluntary blood donors, administration of disposable material in clinics and vaccination by hepatitis B. PMID- 27264920 TI - Some hematological parameters and the prognostic values of CD4, CD8 and total lymphocyte counts and CD4/CD8 cell count ratio in healthy HIV sero-negative, healthy HIV sero-positive and AIDS subjects in Port Harcourt, Nigeria. AB - OBJECTIVE: The present study attempts to determine normal values of CD4, CD8, CD4/CD8 ratio, total WBC and differential counts, hematocrit and total lymphocyte count (TLC) in healthy HIV sero-negative and sero-positive subjects, and to assess the prognostic significance of these parameters in these subjects as compared to AIDS subjects. METHODS: A total of 300 subjects (147 M, 153 F) aged between 17 and 71 years were recruited into the study. Subjects were separated according to sex and divided into three groups: Group A: healthy HIV sero negative subjects; Group B: healthy HIV sero-positive newly diagnosed ART-naive subjects; and Group C: AIDS subjects. CD4 and CD8 counts were determined by flow cytometry; hematocrit was determined using Hawksley micro-capillary tubes; total WBC and differential counts were determined manually with the improved Neubauer counting chamber; and TLC was obtained by multiplying the percentage of lymphocytes by the total WBC count. RESULTS: For male subjects, significant differences were found in CD4 count, CD4/CD8 count ratio, hematocrit, total WBC and TLC, whereas for female subjects, significant differences were found only in CD4 and CD4/CD8 count ratio in the three groups of subjects. In both sexes, however, these parameters were found to be highest in healthy HIV sero-negative subjects and lowest in AIDS subjects, with HIV sero-positive subjects having intermediate values. CONCLUSION: The results confirm previous reports that the CD4 count and CD4/CD8 count ratio are fairly reliable indicators of the progression of HIV infection. In addition, the results also apparently suggest that the prognostic value of CD8 count is limited and that of TLC possibly sex dependent. The results could be of importance in our environment since previous reports have been relatively scarce. PMID- 27264921 TI - The levels of nitric oxide in beta-thalassemia minor. AB - OBJECTIVE: The aim of this study was to investigate the relationship between NO (nitric oxide) and beta-thalassemia minor. METHODS: A total of 60 patients with beta-thalassemia minor (30 M, 30 F) were included in the study. The control group consisted of 60 healthy subjects (30 M, 30 F). Plasma nitrite/nitrate levels were measured using the Griess reaction method and analyzed by spectrophotometry at 545 nm. RESULTS: Plasma direct nitrite, total nitrite and nitrate levels were 7.561+/-6.19, 42.548+/-7.37 and 34.84+/-6.24 in beta-thalassemia minor patients versus 36.9+/-19.8, 85.9+/-35.3 and 48.61+/-17.35 Imol/dl in controls, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in beta-thalassemia minor patients compared with the control group (p<0.001). CONCLUSION: These findings confirm that plasma NO levels in beta thalassemia minor patients are decreased at the time of diagnosis. This may be helpful in assessing the prognosis and follow-up evaluation of patients with beta thalassemia minor. PMID- 27264922 TI - Significance of molecular-cytogenetic aberrations for the achievement of first remission in de novo acute myeloid leukemia. AB - OBJECTIVE: The majority of adults diagnosed with acute myeloid leukemia (AML) display acquired cytogenetic aberrations at presentation. In this article, we present the major cytogenetic findings regarding AML and review their clinical significance for achievement of the first complete remission. METHODS: We studied 71 adult patients with de novo AML, without previous myelodysplasia or alkylating therapy. Conventional cytogenetics and FISH were performed on bone marrow cells. The patients with AML were assigned to 12 subgroups according to established data for cytogenetic, molecular and general laboratory results. The selection of the analyzed parameters is consistent with internationally accepted "prognostic factors" in adult AML. RESULTS: Complete remission upon induction therapy was achieved in 40% of cases (in a mean period of 2.3 months from therapy initiation). The patients with t(15;17) PML-RARA and inv(16)/CBFbeta-MYH11e demonstrated the highest frequency of complete remission. Patients with hypodiploidy, t(9;22)/bcr-abl and complex karyotypes were therapy-resistant or died within the first three months after AML diagnosis. CONCLUSION: Molecular cytogenetic findings have an important significance for achievement of first complete remission. However, laboratory and biologic features (age, WBC and LDH) and type of AML have a large influence on the disease outcome. PMID- 27264923 TI - Scleredema-associated IgA myeloma with myelofibrosis in a young adult: a case report. AB - Scleredema of Buschke is a rare fibromucinous connective tissue disorder of unknown etiology. It is often associated with a benign monoclonal gammopathy and rarely with myelomatosis. We report a case of scleredema-associated IgA myeloma with myelofibrosis in a 24-year-old male patient. Scleredema generally affects young adults and onset of associated monoclonal gammopathy is at a younger age than when not associated with scleredema. However, presentation at a much younger age (24 years in our case) is very unusual. Although mucin deposition in the bone marrow has been reported in scleredema, to the best of our knowledge, myelofibrosis has not been reported. PMID- 27264924 TI - Acute myeloblastic leukemia-associated Marfan syndrome and Davidoff-Dyke-Masson syndrome: a case report. AB - We present herein a 23-year-old man with acute myeloblastic leukemia (AML) associated with Davidoff-Dyke-Masson syndrome (DDMS) and Marfan syndrome (MS). The diagnosis of DDMS was based on findings including left facial asymmetry, left hemiparesis, mental retardation, right cerebral hemiatrophy, dilatation of the ipsilateral lateral ventricle and calvarial thickening. The diagnosis of MS was based on clinical findings including tall stature, myopia, retinitis pigmentosa, blue scleras, scoliosis, pectus excavatum, arachnodactyly and low ratio of upper/lower body segment. The patient developed hepatosplenomegaly, gingival hypertrophy and pancytopenia. Peripheral blood film and bone marrow examination showed that most of nucleated cells were blasts; immunophenotype of those cells showed CD11+, CD13+, CD14+, CD33+ and HLA-DR+. These findings confirmed the diagnosis of AML (FAB-M5). After induction chemotherapy, remission was obtained. To the best of our knowledge, our case is the third report of AML in MS syndrome, while AML associated with DDMS and MS has not been previously reported in the literature. PMID- 27264925 TI - Gum hypertrophy - an unusual presenting feature in a case of precursor T-cell acute lymphoblastic leukemia. AB - Acute lymphoblastic leukemia/lymphoma, the malignant transformation of T-cell or B-cell precursors, is the most common diagnosis in pediatric oncology. Precursor T-cell acute lymphoblastic leukemia/lymphoma commonly affects adolescents, and is associated with mediastinal mass in over half of the cases, with early dissemination to bone marrow, gonads and the central nervous system. We present a rare case of precursor T-cell acute lymphoblastic leukemia/lymphoma with initial oral manifestation, presenting with the unusual features of gum hypertrophy and involvement of upper jaw and palate in a 10-year-old boy. This report discusses the clinical presentation, histopathologic and immunologic features, and diagnosis of this malignancy. PMID- 27264926 TI - The use of high-dose acyclovir in patients with hematological malignancies who develop herpes virus infections: Is it really safe? PMID- 27264927 TI - Failure of yttrium-90 (90Y)-ibritumomab tiuxetan radioimmunotherapy (Zevalin(r)) with fatal side effects in relapsed/refractory diffuse large B-cell NHL transformed from other lymphomas. PMID- 27264929 TI - Insulin-like growth factor-1 and zinc. PMID- 27264928 TI - Allogeneic stem cell transplant in a patient with aplastic anemia with bacteremia and candidemia. PMID- 27264930 TI - A rare presentation of multiple myeloma: Tc-99m MIBI SPECT imaging of orbital involvement. PMID- 27264931 TI - Selective Solid-Phase Extraction of Lead Ions in Water Samples Using Three Dimensional Ion-Imprinted Polymers. AB - Ion-imprinted polymers (IIPs) have drawn much attention in the selective determination of heavy metals. In this study, 8-hydroxyquinoline-grafted gelatin with different types of functional groups was first introduced as a biomolecular monomer to enhance the selectivity of imprinted cavities. Based on its swelling and film-forming properties, a simple strategy containing formation of the hydrogel film, swelling/folding followed by cross-linking, was proposed to prepare three-dimensional IIPs with high adsorption capacity (235.7 mg g(-1)), strong selectivity (imprinted factor was 2.9), and rapid kinetics. Based on the different swelling container, different morphologies of IIPs could be prepared to satisfy the requirements of practical application. Consequently, the IIPs extraction coupled with a spectrophotometric method was applied for determination of lead ions, and the limit of detection was 0.2 ng mL(-1), which could be used for monitoring of Pb(II) in drinking water and surface water. PMID- 27264932 TI - Glucose homeostasis in rats treated with 4-vinylcyclohexene diepoxide is not worsened by dexamethasone treatment. AB - 4-vinilcyclohexene diepoxide (4-VCD) causes premature ovarian failure and may result in estrogen deficiency, characterizing the transition to estropause in rodents (equivalent to menopause in women). Estropause/menopause is associated with metabolic derangements such as glucose intolerance and insulin resistance. Glucocorticoids (GCs) are known to exert diabetogenic effects. Thus, we aimed to investigate whether rats with premature ovarian failure are more prone to the diabetogenic effects of GC. For this, immature female rats received daily injections of 4-VCD [160mg/kg body weight (b.w.), intraperitoneally (i.p.)] for 15 consecutive days, whereas control rats received vehicle. After 168days of the completion of 4-VCD administration, rats were divided into 4 groups: CTL-received daily injections of saline (1mL/kg, b.w., i.p.) for 5days; DEX-received daily injections of dexamethasone (1mg/kg, b.w., i.p.) for 5days; VCD-treated as CTL group; VCD+DEX-treated as DEX group. Experiments and euthanasia occurred one day after the last dexamethasone injection. 4-VCD-treated rats exhibited ovary hypotrophy and reduced number of preantral follicles (p<0.05). Premature ovarian failure had no impact on the body weight gain or food intake, but both were reduced by the effects of dexamethasone. The increase in blood glucose, plasma insulin and triacylglycerol levels as well as the reduction in insulin sensitivity caused by dexamethasone treatment was not exacerbated in the VCD+DEX group of rats. Premature ovarian failure did change neither the hepatic content of glycogen and triacylglycerol nor the glycerol release from perigonadal adipose tissue. Glucose intolerance was observed in the VCD group after an ipGTT (p<0.05), but not after an oral glucose challenge. Glucose intolerance and compensatory pancreatic beta-cell mass caused by GC were not modified by ovarian failure in the VCD+DEX group. We conclude that reduced ovarian function has no major implications on the diabetogenic effects promoted by GC treatment, indicating that other factors related to aging may make rats more vulnerable to GC side effects on glucose metabolism. PMID- 27264933 TI - In situ detection of estrogen receptor dimers in breast carcinoma cells in archival materials using proximity ligation assay (PLA). AB - Estrogen receptor (ER) is required for carcinoma cell proliferation in the great majority of breast cancer and also functions as a dimer. ER dimeric proteins have been largely identified by BRET/FRET analyses but their in situ visualization have not yet been reported. Recently, in situ Proximity Ligation Assay (PLA) has been developed as the methods detecting protein interactions in situ. Therefore, in this study we firstly demonstrated the dimerization of ERalpha in breast carcinoma cell lines and tissues using PLA. The human breast carcinoma cell lines MCF-7, T-47D and MDA-MB-231 were used in this study. Cells were treated with ER agonist or antagonist and fixed in 4% PFA, and ER dimers were subsequently detected using PLA. The evaluation of ER dimers in breast carcinoma cell lines were quantified by measuring the area of dots localized in the nuclei using image analysis. We also firstly demonstrated the visualization of ER dimer patterns in 10% formalin-fixed paraffin-embedded tissues of breast cancer using PLA technique. Estradiol (E2) administration induced ERalpha homodimers in the nuclei of MCF-7 and T-47D but not in ER-negative MDA-MB-231. 4-OH tamoxifen also induced ERalpha homodimers but the subcellular localization of these ERalpha homodimers was predominant in cytoplasm instead of the nuclei induced by E2 treatment. ICI182,780 treatment did decrease the number of formation of ERalpha homodimers in MCF-7. In breast cancer patients, ERalpha PLA score was significantly correlated positively with ERalpha- or PgR (progesterone receptor) immunohistochemical scores and inversely with Ki-67-labeling index, respectively. We also demonstrated the ERalpha/beta heterodimer as well as ERalpha homodimers in both breast carcinoma cell lines and surgical pathology specimens. In summary, we did firstly succeed in the visualization of ER dimeric proteins using PLA method. The evaluation of ER dimer patterns could provide pivotal information as to the prediction of response to endocrine therapy of breast cancer patients. PMID- 27264934 TI - Wide-field time-gated photoluminescence microscopy for fast ultrahigh-sensitivity imaging of photoluminescent probes. AB - Fluorescence microscopy is a fundamental technique for the life sciences, where biocompatible and photostable photoluminescence probes in combination with fast and sensitive imaging systems are continually transforming this field. A wide field time-gated photoluminescence microscopy system customised for ultrasensitive imaging of unique nanoruby probes with long photoluminescence lifetime is described. The detection sensitivity derived from the long photoluminescence lifetime of the nanoruby makes it possible to discriminate signals from unwanted autofluorescence background and laser backscatter by employing a time-gated image acquisition mode. This mode enabled several-fold improvement of the photoluminescence imaging contrast of discrete nanorubies dispersed on a coverslip. It enabled recovery of the photoluminescence signal emanating from discrete nanorubies when covered by a layer of an organic fluorescent dye, which were otherwise invisible without the use of spectral filtering approaches. Time-gated imaging also facilitated high sensitivity detection of nanorubies in a biological environment of cultured cells. Finally, we monitor the binding kinetics of nanorubies to a functionalised substrate, which exemplified a real-time assay in biological fluids. 3D-pseudo colour images of nanorubies immersed in a highly fluorescent dye solution. Nanoruby photoluminescence is subdued by that of the dye in continuous excitation/imaging (left), however it can be recovered by time-gated imaging (right). At the bottom is schematic diagram of nanoruby assay in a biological fluid. PMID- 27264936 TI - Long-term patterns in Iberian hare population dynamics in a protected area (Donana National Park) in the southwestern Iberian Peninsula: Effects of weather conditions and plant cover. AB - The Iberian hare (Lepus granatensis) is a widely distributed endemic species in the Iberian Peninsula. To improve our knowledge of its population dynamics, the relative abundance and population trends of the Iberian hare were studied in the autumns of 1995-2012 in a protected area (Donana National Park) by spotlighting in 2 different habitats: marshland and ecotones. The average relative abundance was 0.38 hare/km (SD = 0.63) in the marshland and 3.6 hares/km (SD = 4.09) in ecotones. The Iberian hare population exhibited local interannual fluctuations and a negative population trend during the study period (1995-2012). The results suggest that its populations are in decline. The flooding of parts of the marshland in June, July and October favor hare abundance in the ecotone. Hare abundance in the marshland increases as the flooded surface area increases in October. These effects are more pronounced if the rains are early (October) and partially flood the marsh. By contrast, when marsh grasses and graminoids are very high and thick (as measured using the aerial herbaceous biomass [biomass marshland] as a proxy), the abundance of hares decreases dramatically as does the area of the marsh that is flooded (in November). PMID- 27264935 TI - The tumor suppressor gene lkb1 is essential for glucose homeostasis during zebrafish early development. AB - The liver kinase B1 (LKB1) is encoded by tumor suppressor gene STK11, which is mutated in Peutz-Jeghers syndrome patients. Lkb1 plays indispensable roles in energy homeostasis. However, how Lkb1 regulates energy homeostasis in vivo remains to be fully understood. We found that inactivation of zebrafish Lkb1 upregulates pyruvate dehydrogenase kinase 2 expression and inactivates pyruvate dehydrogenase complex by increasing phosphorylation of pyruvate dehydrogenase. As a result, glycolysis is significantly enhanced as indicated by increased lactate production, which resembles the Warburg effect in cancer cells. Inhibition of Pdk2 in lkb1 mutants with dichloroacetate, a promising anticancer drug, rescued the lactate production to wild-type level, suggesting the lkb1 mutant may be used to screen compounds targeting aerobic glycolysis in cancer therapy. PMID- 27264938 TI - Spectroscopic investigation into the design of solid-acid catalysts for the low temperature dehydration of ethanol. AB - The increased demand for bulk hydrocarbons necessitates research into increasingly sustainable, energy-efficient catalytic processes. Owing to intricately designed structure-property correlations, SAPO-34 has become established as a promising material for the low temperature ethanol dehydration to produce ethylene. However, further optimization of this process requires a precise knowledge of the reaction mechanism at a molecular level. In order to achieve this a range of spectroscopic characterization techniques are required to probe both the interaction with the active site, and also the wider role of the framework. To this end we employ a combination of in situ infra-red and neutron scattering techniques to elucidate the influence of the surface ethoxy species in the activation of both diethyl ether and ethanol, towards the improved formation of ethylene at low temperatures. The combined conclusions of these studies is that the formation of ethylene is the rate determining step, which is of fundamental importance towards the development of this process and the introduction of bio-ethanol as a viable feedstock for ethylene production. PMID- 27264937 TI - Erratum to: Hierarchical modeling identifies novel lung cancer susceptibility variants in inflammation pathways among 10,140 cases and 11,012 controls. PMID- 27264939 TI - Effect of Finishing and Polishing on the Surface Roughness of Four Ceramic Materials after Occlusal Adjustment. AB - PROBLEM: Intraoral occlusal adjustment of ceramic restorations can create a significant increase in surface roughness that can produce wear of the opposing dentition. PURPOSE: To compare the surface roughness of glazed and polished monolithic ceramics with the surface roughness produced by different intraoral polishing systems on adjusted monolithic ceramics. MATERIALS AND METHODS: Milled ceramic discs (10 mm diameter * 2 mm thickness) were manufactured and distributed according to the following groups (n = 10): BruxZir (glazed and polished), Zenostar (glazed and polished), IPS Empress CAD, and IPS e.max CAD. Surface roughness, expressed as arithmetic average height (Ra ), was measured using atomic force microscope and profilometer before and after adjustment and polishing with the following intraoral polishing systems: BruxZir and Dialite ZR (for BruxZir), Zenostar and Dialite ZR (for Zenostar), and OptraFine and Dialite LD for IPS Empress CAD and IPS e.max CAD. Mean and standard error for each material and polishing system were calculated. T-test, one-way ANOVA, and Bonferroni post hoc tests were used to analyze data. RESULTS: BruxZir zirconia presented smoother surfaces with Dialite ZR system compared to BruxZir system, Zenostar zirconia shown smoother surfaces with Zenostar system compared to Dialite ZR system and IPS Empress CAD and IPS e.max CAD presented smoother surfaces with OptraFine system in comparison to Dialite LD system. CONCLUSION: All materials presented smoother surfaces at baseline than after adjustment and polishing. CLINICAL SIGNIFICANCE: This paper reveals the results of an in vitro study that provides information to clinicians regarding which intraoral polishing system will produce a smoother surface after the adjustment and polishing of IPS Empress CAD, IPS e.max CAD, BruxZir and Zenostar ceramic materials. (J Esthet Restor Dent 28:382-396, 2016). PMID- 27264940 TI - Diagnostic yield and complications of transthoracic computed tomography-guided biopsies. AB - INTRODUCTION: The widespread use of computed tomography (CT) improves detection of pulmonary lesions, which are not only detected at an increased rate but also at a smaller size. CT-guided lung biopsies are now more frequently used than fluoroscopy-guided lung biopsies. The main aim of the present paper was to investigate the outcome and complications of the biopsies. METHODS: We retrospectively collected the results and information from 520 CT-guided thorax biopsies. All biopsies were performed with CT-guided "beam-through" technique, using a 64-slice CT scanner. RESULTS: In 86% of the biopsies, the tissue material was found to be sufficient. In 32% of the biopsies, a complication arose, mostly pneumothorax (30%), but chest drainage was needed in only 15% of the 520 cases. Patients with more than ten cigarette pack-years had a complication risk that was twice as high at that of patients with fewer pack-years. We found that the risk of pneumothorax increased the further the lesion was from the skin surface, the smaller the lesions were and when the patient was biopsied in a lateral position. We also found a higher risk of complications in females than in males. CONCLUSIONS: CT-guided biopsy is an excellent tool for analysing pulmonary lesions. The present study clearly shows that the risk of developing a pneumothorax is significantly increased among smokers and former smokers with more than ten pack-years. FUNDING: none. TRIAL REGISTRATION: not relevant. PMID- 27264941 TI - Diagnostic packages can be assigned accurately in emergency departments. A multi centre cohort study. AB - INTRODUCTION: In the Region of Southern Denmark, the emergency departments categorise patients based on presenting symptoms and a proposed diagnostic package (n = 40) within each category. The diagnostic packages describe relevant clinical information and standard laboratory and other investigations to be performed. Allocation to the right diagnostic package is assumed to be associated with a higher quality. The aim of this study was to describe to which degree the assigned symptom-based diagnostic packages are related to relevant discharge diagnoses. METHODS: This was a descriptive cohort study. The analysis was based on data on assigned diagnostic package, patient discharge diagnosis, hospital, gender, age, time of admission and discharge, length of stay, diagnostic package assigned, discharge diagnosis and co-morbidity. An acceptable standard for what would be an appropriate primarily diagnostic package was developed using a modified Delphi method. RESULTS: A total of 16,543 patient contacts were identified. Women constituted 52.2% (n = 8,925) of the patients. The median age was 64 years and the median length of stay was one day. All diagnostic packages were represented. A total of 68% of the included patients had been assigned an acceptable diagnostic package (95% confidence interval: 67.2-68.7). We found an appropriate use of one of 30 diagnostic packages in more than 50% of the cases. CONCLUSIONS: We found that 68% of the included patients were assigned an acceptable diagnostic package and that about 80% of all acute pathways were covered by 14 diagnostic packages. FUNDING: The study was funded by Region of Southern Denmark. TRIAL REGISTRATION: The study was registered with the Danish Data Protection Agency (No. 2008-58-0035). No further approval was required. PMID- 27264942 TI - Environmental needs in childhood disability analysed by the WHO ICF, Child and Youth Version. AB - INTRODUCTION: The WHO has launched a common classification for disabilities in children, the International Classification of Functioning, Disability and Health, Child and Youth Version (ICF-CY). We wanted to determine whether cat-egories of the environmental (e) and the body functions (b) components of the classification could address environmental needs in children with different disorders and various disability severities. METHODS: A set of 16 e categories and 47 b categories were selected and worded to best enable parents to describe children's everyday support needs and environmental influences through interviews in their own homes. RESULTS: Of the 367 invited parents, 332 (90.5%) participated, providing data on children with spina bifida, spinal muscular atrophy, muscular disorders, cerebral palsy, visual impairments, hearing impairments, mental disability and disabilities following brain tumour treatment. The mean age of children across disabilities was 9.4 years (range: 1.0-15.9). The mean e code score was 35.7 (range: 4.0-64.0), and the mean b code score was 32.2 (range: 0.0 159.0). The most urgent needs as detected by qualifier 4 environmental categories scores were common among children with complex disorders and issues related to health professionals, legal services and health services. CONCLUSIONS: Parents understand the environmental and body function components in a meaningful manner and the codes seem to be valid. Special emphasis should be given to environmental issues for children with more complex disabilities. There was no correlation between the severity of a disability and environmental issues, indicating that each child's needs were basically met, irrespective of disability severity. FUNDING: partnership project S 16, 21, 31 administered by the Danish Health Authority. TRIAL REGISTRATION: not relevant. PMID- 27264943 TI - Learning and feedback from the Danish patient safety incident reporting system can be improved. AB - INTRODUCTION: The perceived usefulness of incident reporting systems is an important motivational factor for reporting. The usefulness may be facilitated by well-established feedback mechanisms and by learning processes. The aim of this study was to investigate how feedback mechanisms and learning processes were implemented at four Danish hospital units all located in one of the five Danish regions. METHODS: Based on the concepts of feedback and learning from incident processes, a questionnaire was developed and distributed to 335 patient safety representatives from 200 departments at four Danish hospital units in one of the five Danish regions. RESULTS: The study showed that external reporters were rarely contacted for dialogue, grouped front-line staff were sparsely involved in the learning process, few evaluated the effectiveness of implemented interventions and personal factors were frequently perceived as a primary contributory factor to these incidents. In contrast, the patient safety representatives perceived their competencies as sufficient for the job, internal reporters were often contacted for dialogue, evaluation was widely used and management supported the work with incident reports. CONCLUSIONS: The results of the study identified several shortcomings in the implementation of learning processes and feedback mechanisms. The apparent existence of a person-focused approach stands out as an element of notice. The insufficient implementation we observed indicates that there is room for improvement in the efforts made to maximise learning from incidents in the investigated population. FUNDING: not relevant. TRIAL REGISTRATION: not relevant. PMID- 27264944 TI - The immune response is affected for at least three weeks after extensive surgery for ovarian cancer. AB - INTRODUCTION: The treatment of women with ovarian cancer in advanced stages consists of extensive surgery followed by chemotherapy initiated three weeks after surgery. In this study, selected immune parameters were investigated to elucidate when the immune system is normalised following the operation. METHODS: Ten women undergoing extensive surgery for ovarian cancer were compared with a control group of ten women undergoing abdominal hysterectomy for a benign diagnosis. Blood samples were collected over a period of 21 days post operatively. The levels of interleukin-6, interleukin-8, interleukin-10 and the activity and total frequency of natural killer cells were measured. RESULTS: Interleukin-6 and interleukin-10 were significantly elevated immediately after the operation and also after 21 days. The total population of natural killercells and the total activity were reduced. The total activity of natural killer-cells did not normalise within 21 days. CONCLUSIONS: The level of the cytokines interleukin-6 and interleukin-10 is increased 21 days after the operation, and the function of natural killer cells is not normalised at 21 days after surgery. FUNDING: The study received funding from Odense University Hospital Free Research Fund. TRIAL REGISTRATION: not relevant. PMID- 27264945 TI - Effect of clonidine to prevent agitation in children after sevoflurane anaesthesia: a randomised placebo controlled multicentre trial. AB - INTRODUCTION: Post-operative agitation (PA) is a common problem (20-70%) in children anaesthetised with sevoflur-ane. Clonidine is widely used off-label in children for several indications, including PA, but the current level of evidence is limited. Our aim is to investigate the impact of prophylactic intravenous (IV) clonidine administered at the end of surgery on the incidence and degree of PA. Furthermore, the pharmacokinetic profile of IV clonidine in children is not well established and our aim is to obtain pharmacokinetic data relating hereto. METHODS: This is a multicentre, randomised and blinded clinical trial in which we will be enrolling 380 children aged 1-5 years who are planned for anaesthesia with sevoflurane and fentanyl. Inclusion is based on computer-generated randomisation (1:1) and stratified by age and site. The study drug is administered IV approximately 20 min. before the expected completion of surgery (intervention: clonidine 3 ug per kg; placebo: equal quantity of saline). CONCLUSION: The primary outcome is PA measured on the Watcha scale. The secondary outcomes include post-operative pain relief and adverse effects, including a 30 day follow-up. In total, 40 children will be allocated to drug assay sampling, enabling a compartmental pharmacokinetic analysis. FUNDING: Funded by the participating departments and by two unrestricted scientific grants from the Danish Society of Anaesthesia and Intensive. TRIAL REGISTRATION: This study was approved by the Danish Health and Medicines Authority (EudraCT number 2014-001466 10), the Ethics Committee of the Capital Region of Denmark (H-2-2014-072) and registered with Clinicaltrials.gov (NCT02361476). PMID- 27264946 TI - Establishment and use of surgical rat models for assessment of organ specific in vivo clearance. AB - Knowledge of clearance plays a key role in the development of new drug entities, especially in the development of improved analogues for treatment of chronic conditions. Improved pharmacokinetic properties can be used to increase dosing interval and thereby improve patient compliance. This will lead to improved treatment outcome or decreased risk of treatment failure when treating chronic conditions. Therefore, animal models for assessment of organ-specific clearance are of great value in preclinical drug development. These models can be used to obtain insights into the relative importance of a clearance organ and thereby guide drug design of new analogues in early drug discovery. The current PhD project was undertaken to explore surgical in vivo models, which could be used in the assessment of the relative importance of major clearance organs. It was the aim of the PhD project to establish and validate both a nephrectomy model and a hepatectomy model as tools to investigate relative importance of renal and hepatic clearance. Furthermore, the project aim was to investigate renal clearance of rFVIIa and rhGH using a nephrectomy model in rats. The thesis is composed of a short theoretical background, a literature review, two papers based on experimental work as well as experimental work not included in the papers. Chapter one is an introduction with the specific aims and hypotheses. The chapters from two to five contain theoretical background of the clearance concept, anatomical and physiological description of clearance organs and a brief overview of potential clearance models including in vivo models. Chapters six through nine highlight the experimental work with the results obtained during the PhD project. Lastly, the chapters from ten to twelve contain a general discussion, conclusion and perspectives of the current thesis. Paper I "Nephrectomized and hepatectomized animal models as tools in preclinical pharmacokinetics" provides a literature review of animal models previously used as tools to investigate renal and hepatic clearance. An overview of the surgical procedures previously described for establishment of in vivo nephrectomy and hepatectomy models is given. Many different surgical methods have been employed in the attempt to make anephric or anhepatic in vivo models. The overall conclusion of the literature review was that a suitable clearance model would require only one surgical procedure. Furthermore, the clearance studies should be conducted immediately after completed surgery to decrease the impact on other clearance pathways and physiology in general. Paper II "The kidneys play an important role in the clearance of rFVIIa in rats" describes the establishment, validation and use of an in vivo model for assessment of renal clearance. The model employed was a rat nephrectomy model and the compounds investigated were inulin and rFVIIa. General physiology was assumed to be close to normal as rectal temperature, oxygen saturation and pulse were within normal range during the pharmacokinetic studies. Nephrectomy significantly reduced clearance of rFVIIa and almost completely abolished clearance of inulin. Thus, it was concluded that the nephrectomy model could be used in assessment of the relative importance of the kidneys in the clearance of rFVIIa and the data obtained indicate that renal clearance accounts for 50% of total body clearance of rFVIIa. Paper III "The kidneys play a central role in the clearance of rhGH in rats" addresses renal clearance of rhGH. The in vivo model established in Paper II was used in a pharmacokinetic study of rhGH to assess the relative importance of the kidneys in the clearance of rhGH. The conclusion drawn based on this study was that the kidneys account for 90% of total body clearance of rhGH in anaesthetized rats. Furthermore, it was noted that anaesthesia reduced clearance of rhGH by 36% compared to non-anaesthetized rats. In conclusion, establishment, validation and use of a rat nephrectomy model as a tool to investigate renal clearance was successful, but an in vivo rat model of hepatic clearance model was not successfully established. PMID- 27264947 TI - Laser-assisted delivery of topical methotrexate - in vitro investigations. AB - Ablative fractional lasers (AFXL) are increasingly used to treat dermatological disorders and to facilitate laser-assisted topical drug delivery. In this thesis, laser-tissue interactions generated by stacked pulses with a miniaturized low power 2,940 nm AFXL were characterized (study I). Knowledge of the correlation between laser parameters and tissue effects was used to deliver methotrexate (MTX) topically through microscopic ablation zones (MAZs) of precise dimensions. MTX is a well-known chemotherapeutic and anti-inflammatory drug that may cause systemic adverse effects, and topical delivery is thus of potential benefit. The impact of MAZ depth (study II) and transport kinetics (study III) on MTX deposition in skin as well as transdermal permeation was determined in vitro. Quantitative analyses of dermal and transdermal MTX concentrations were performed by high performance liquid chromatography (HPLC) (study II & III), while qualitative analyses of MTX biodistribution in skin were illustrated and semi quantified by fluorescence microscopy (study II & III) and desorption electro spray mass spectrometry imaging (DESI-MSI) (study III). Laser-tissue interactions generated by AFXL: AFXL-exposure generated a variety of MAZ-dimensions. MAZ depth increased linearly with the logarithm of total energy delivered by stacked pulses, but was also affected by variations in power, pulse energy, pulse duration, and pulse repetition rate. Coagulation zones lining MAZs increased linearly with the applied total energy, while MAZ width increased linearly with the logarithm of stacked pulses. Results were gathered in a mathematical model estimating relations between laser parameters and specific MAZ dimensions. Impact of MAZ depth on AFXL-assisted topical MTX delivery: Pretreatment by AFXL facilitated topical MTX delivery to all skin layers. Deeper MAZs increased total MTX deposition in skin compared to superficial MAZs and altered the intradermal biodistribution profile towards maximum accumulation in deeper skin layers. Biodistribution of MTX occurred throughout the skin without being compromised by coagulation zones of varying thickness. The ratio of skin deposition versus transdermal permeation was constant, regardless of MAZ depth. Impact of transport kinetics on AFXL-assisted topical MTX delivery: MTX accumulated rapidly in AFXL processed skin. MTX was detectable in mid-dermis after 15 min. and saturated the skin after 7 h at a ten-fold increased MTX-concentration compared to intact skin. Transdermal permeation stayed below 1.5% of applied MTX before skin saturation, and increased afterwards up to 8.0% at 24h. MTX distributed radially into the coagulation zone within 15 min of application and could be detected in surrounding skin at 1.5 h. Upon skin saturation, MTX had distributed in an entire mid-dermal skin section. In conclusion, adjusting laser parameters and application time may enable targeted treatments of dermatological disorders and potentially pose a future alternative to systemic MTX in selected dermatological disorders. PMID- 27264948 TI - Antipsychotic Induced Dopamine Supersensitivity Psychosis: A Comprehensive Review. AB - Chronic prescription of antipsychotics seems to lose its therapeutic benefits in the prevention of recurring psychotic symptoms. In many instances, the occurrence of relapse from initial remission is followed by an increase in dose of the prescribed antipsychotic. The current understanding of why this occurs is still in its infancy, but a controversial idea that has regained attention recently is the notion of iatrogenic dopamine supersensitivity. Studies on cell cultures and animal models have shown that long-term antipsychotic use is linked to both an upregulation of dopamine D2-receptors in the striatum and the emergence of enhanced receptor affinity to endogenous dopamine. These findings have been hypothesized to contribute to the phenomenon known as dopamine supersensitivity psychosis (DSP), which has been clinically typified as the foundation of rebound psychosis, drug tolerance, and tardive dyskinesia. The focus of this review is the update of evidence behind the classification of antipsychotic induced DSP and an investigation of its relationship to treatment resistance. Since antipsychotics are the foundation of illness management, a greater understanding of DSP and its prevention may greatly affect patient outcomes. PMID- 27264949 TI - Acetylshikonin from Zicao exerts antifertility effects at high dose in rats by suppressing the secretion of GTH. AB - Zicao is being highlighted as a promising Chinese medicine due to all the beneficial effects that have been associated with its use. Unfortunately, studies on the toxicity of Zicao in different species are still missing and should be carried out. In this study, we investigated whether Acetylshikonin (AS) from Zicao has an anti-fertility effect through mating experiments and explored its underling mechanism. Sprague-Dawley rats received no treatment or were treated with 120, 360 or 1080 mg/kg AS extract by intragastric administration for 2 weeks. The rat pregnancy rate of the 1080 mg/kg dose group was significantly decreased relative to control group, while it recovered after a month of drug withdrawal, which indicated that the effect of antifertility is reversible. Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels in rat were significantly decreased by AS. The secretion of FSH in rat anterior pituitary cells was decreased but the synthesis was not affected. AS reduced the number of developing follicle and mature follicle in rat ovarian cortical. Maybe all of these resulted from AS decreased the expression of synaptotagmin-1 and SNAP-25 which were the critical proteins of exocytosis. Our data suggested that AS at high dose can suppress the ability of pregnancy of the rats through decreasing serum FSH and LH levels by affecting exocytosis process of gonadotropic hormone (GTH). PMID- 27264950 TI - A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines. AB - Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA. From sequencing analysis, this additional band was a selective splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene, producing the transcript that encodes truncated peptide lacking 20 amino acids at the middle of preprohepcidin. In the present study, we used the digital PCR, because such a small amount of variant mRNA was difficult to quantitate by the conventional RT-PCR amplification. Among seven hepatoma-derived cell lines, six cell lines have significant copy numbers of this variant mRNA, but not in one cell line. In the transient transfection analysis of variant-type hepcidin cDNA, truncated preprohepcidin has a different character comparing with native preprohepcidin: its product is insensitive to digestion, and secreted into the medium as a whole preprohepcidin form without maturation. Loss or reduction of function of HAMP gene by aberrantly splicing may be a suitable phenomenon to obtain the proliferating advantage of hepatoma cells. PMID- 27264951 TI - The properties of the actin-myosin interaction in the heart muscle depend on the isoforms of myosin but not of alpha-actin. AB - In myocardium of mammals there are two isoforms of myosin heavy chains, alpha and beta. In ventricle, together with ventricular isoforms of light chains they form two isomyosins: V1 and V3, homodimers of alpha- and beta-heavy chains, respectively. In atria, alpha- and beta-heavy chains together with atrial light chains form A1 (alphaalpha) and A2 (betabeta) isomyosins. Besides in myocardium two isoforms of alpha-actin, skeletal and cardiac, are expressed. We assume that the differences in the amino acid sequence of cardiac and skeletal actin may affect its interaction with myosin. To test this hypothesis, we investigated characteristics of actin-myosin interactions of cardiac and skeletal isoforms of alpha-actin with the isoforms of cardiac myosin using an optical trap technique and an in vitro motility assay. It was found that the mechanical and kinetic characteristics of the interactions of the isoforms of cardiac myosin with actin depend on the isoforms of myosin not alpha-actin. PMID- 27264952 TI - miR-411-5p inhibits proliferation and metastasis of breast cancer cell via targeting GRB2. AB - miR-411-5p (previously called miR-411) is severely involved in human diseases, however, the relationship between miR-411-5p and breast cancer has not been investigated thoroughly. Here, we found that the expression of miR-411-5p was downregulated in breast cancer tissues compared with their matched adjacent non neoplastic tissues. In addition, the expression of miR-411-5p was also lower in breast cancer cell lines in contrast with MCF-10A. Moreover, we investigated the target and mechanism of miR-411-5p in breast cancer using mimic and inhibitor, and demonstrated the involvement of GRB2 and Ras activation. Ectopic expression of miR-411-5p suppressed the breast cancer cell proliferation, migration and invasion while low expression of miR-411-5p exhibited the opposite effect. Furthermore, GRB2 was demonstrated to be significantly overexpressed in breast cancer tissues compared with normal tissues, and low expression of GRB2 had a longer overall survival compared with high expression of GRB2 in breast cancer. In general, our study shed light on the miR-411-5p related mechanism in the progression of breast cancer and, miR-411-5p/GRB2/Ras axis is potential to be molecular target for breast cancer therapy. PMID- 27264953 TI - Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes. AB - Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with the induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. PMID- 27264954 TI - Amphipathic helical ordering of the flagellar secretion signal of Salmonella flagellin. AB - Export of external flagellar proteins requires a signal located within their N terminal disordered part, however, these regions do not share any significant sequence similarity suggesting that the secondary/tertiary structure might be important for recognition by the export gate. NMR experiments were performed to reveal the conformational properties of the flagellin signal sequence in vitro. It assumed a largely disordered fluctuating structure in aqueous environment, but acquired a folded structure containing an amphipathic helical portion in 50% MeOH or upon addition of SDS micelles which are known to promote hydrophobic interactions. Our observations raise the possibility that the signal sequence may partially undergo amphipathic helical ordering upon interaction with the recognition unit of the flagellar export machinery in a similar way as revealed for protein import into intracellular eukaryotic organelles mediated by targeting signals of high diversity. PMID- 27264955 TI - STAT5A and STAT5B have opposite correlations with drug response gene expression. AB - INTRODUCTION: STAT5A and STAT5B are important transcription factors that play a key role in regulation of several important physiological processes including proliferation, survival, mediation of responses to cytokines and in regulating gender differences in drug response genes such as the hepatic cytochrome P450s (CYPs) that are responsible for a large majority of drug metabolism reactions in the human body. STAT5A and STAT5b have a high degree of sequence homology and have been reported to have largely similar functions. Recent studies have, however, indicated that they can also often have distinct and unique roles in regulating gene expression. OBJECTIVE: In this study, we evaluated the association of STAT5A and STAT5B mRNA expression levels with those of several key hepatic cytochrome P450s (CYPs) and hepatic transcription factors (TFs) and evaluated the potential roles of STAT5A and 5b in mediating gender differences in these CYPs and TFs. METHODS: Expression profiling for major hepatic CYP isoforms and transcription factors was performed using RNA sequencing (RNA-seq) in 102 human liver samples (57 female, 45 male). Real time PCR gene expression data for selected CYPs and TFs was available on a subset of 50 human liver samples (25 female, 25 male) and was used to validate the RNA-seq findings. RESULTS: While STAT5A demonstrated significant negative correlation with expression levels of multiple hepatic transcription factors (including NR1I2 and HNF4A) and DMEs such as CYP3A4 and CYP2C19, STAT5B expression was observed to demonstrate positive associations with several CYPs and TFs analyzed. As STAT5A and STAT5B have been shown to be important in regulation of gender differences in CYPs, we also analyzed STAT5A and 5b associations with CYPs and TFs separately in males and females and observed gender dependent differential associations of STATs with several CYPs and TFs. Results from the real time PCR validation largely supported our RNA-seq findings. CONCLUSIONS: Using both RNA sequencing and real time PCR, we examined the association of STAT5A and STAT5B mRNA expression with CYP and TF gene expression. While STAT5A demonstrated significant negative correlations with expression levels of multiple hepatic TFs (including NR1I2 and HNF4alpha) and CYPs (eg. CYP3A4, CYP2C19), STAT5B expression was observed to demonstrate positive association with most of the CYPs/TFs analyzed suggesting that STAT5A and STAT5b have potentially different and distinct roles in regulating expression of hepatic drug response genes. Further studies are needed to elucidate the potential roles of STAT5A and 5b in regulation of CYPs/TFs and the potential implications of these findings. PMID- 27264956 TI - Gain of BDNF Function in Engrafted Neural Stem Cells Promotes the Therapeutic Potential for Alzheimer's Disease. AB - Stem cell-based therapy is a potential treatment for neurodegenerative diseases, but its application to Alzheimer's disease (AD) remains limited. Brain-derived neurotrophic factor (BDNF) is critical in the pathogenesis and treatment of AD. Here, we present a novel therapeutic approach for AD treatment using BDNF overexpressing neural stem cells (BDNF-NSCs). In vitro, BDNF overexpression was neuroprotective to beta-amyloid-treated NSCs. In vivo, engrafted BDNF-NSCs derived neurons not only displayed the Ca(2+)-response fluctuations, exhibited electrophysiological properties of mature neurons and integrated into local brain circuits, but recovered the cognitive deficits. Furthermore, BDNF overexpression improved the engrafted cells' viability, neuronal fate, neurite complexity, maturation of electrical property and the synaptic density. In contrast, knockdown of the BDNF in BDNF-NSCs diminished stem cell-based therapeutic efficacy. Together, our findings indicate BDNF overexpression improves the therapeutic potential of engrafted NSCs for AD via neurogenic effects and neuronal replacement, and further support the feasibility of NSC-based ex vivo gene therapy for AD. PMID- 27264958 TI - Orexin-A stimulates the expression of GLUT4 in a glucose dependent manner in the liver of orange-spotted grouper (Epinephelus coioides). AB - Orexins are hypothalamic neuropeptides involved in the central regulation of feeding behavior, sleep-wake cycle and other physiological functions. Orexin-A can regulate energy metabolism and increase glucose uptake, suggesting a role in glucose metabolism. In this study, we investigated the effects of orexin-A on GLUT4 mRNA and protein levels and the intracellular signaling mechanisms mediating orexin-A activity in the hepatocytes of grouper. Our results demonstrate that intraperitoneal injection of orexin-A increased the expression of GLUT4 in the liver, and this effect was significantly enhanced by co-injection of glucose. Treatment of primary cultured hepatocytes with either orexin-A or glucose alone had no effect on the expression of GLUT4, while co-treatment with orexin-A and glucose significantly increased the expression of GLUT4. This stimulatory effect was partially blocked by inhibitors to ERK1/2, JNK or p38 MAPK and was further blocked by an orexin receptor antagonist, which indicates that orexin-A could stimulate the expression of GLUT4 in a glucose dependent manner in primary hepatocytes via ERK1/2, JNK and p38 signaling. Our results suggest that orexin-A could play a pivotal role in stimulating glucose utilization in grouper, for a long-term goal, which might be useful in reducing costs in the aquaculture industry. PMID- 27264957 TI - Oxygen concentration affects upper thermal tolerance in a terrestrial vertebrate. AB - We tested the oxygen limitation hypothesis, which states that animals decline in performance and reach the upper limits of their thermal tolerance when the metabolic demand for oxygen at high temperatures exceeds the circulatory system's ability to supply adequate oxygen, in air-breathing lizards exposed to air with different oxygen concentrations. Lizards exposed to hypoxic air (6% O2) gaped, panted, and lost their righting response at significantly lower temperatures than lizards exposed to normoxic (21% O2) or hyperoxic (35% O2) air. A greater proportion of lizards in the hyperoxic treatment were able to withstand body temperatures above 44 degrees C than in the normoxic treatment. We also found that female lizards had a higher panting threshold than male lizards, while sex had no effect on gaping threshold and loss of righting response. Body size affected the temperature at which lizards lost the righting response, with larger lizards losing the response at lower temperatures than smaller lizards when exposed to hypoxic conditions. These data suggest that oxygen limitation plays a mechanistic role in the thermal tolerance of lizards. PMID- 27264959 TI - Prediction of change in protein unfolding rates upon point mutations in two state proteins. AB - Studies on protein unfolding rates are limited and challenging due to the complexity of unfolding mechanism and the larger dynamic range of the experimental data. Though attempts have been made to predict unfolding rates using protein sequence-structure information there is no available method for predicting the unfolding rates of proteins upon specific point mutations. In this work, we have systematically analyzed a set of 790 single mutants and developed a robust method for predicting protein unfolding rates upon mutations (Deltalnku) in two-state proteins by combining amino acid properties and knowledge-based classification of mutants with multiple linear regression technique. We obtain a mean absolute error (MAE) of 0.79/s and a Pearson correlation coefficient (PCC) of 0.71 between predicted unfolding rates and experimental observations using jack-knife test. We have developed a web server for predicting protein unfolding rates upon mutation and it is freely available at https://www.iitm.ac.in/bioinfo/proteinunfolding/unfoldingrace.html. Prominent features that determine unfolding kinetics as well as plausible reasons for the observed outliers are also discussed. PMID- 27264960 TI - When to suspect tinea; a histopathologic study of 103 cases of PAS-positive tinea. AB - BACKGROUND: The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis METHODS: We retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid-Schiff (PAS) staining. For each case, gender, biopsy site, and pre-biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted. RESULTS: Concordance between pre-biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted. CONCLUSION: This study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically. PMID- 27264961 TI - Corrigendum: The solvation of electrons by an atmospheric-pressure plasma. PMID- 27264962 TI - Aminoglycosides: old friend...new foe? PMID- 27264963 TI - Beyond the lungs: The new GI frontier. PMID- 27264964 TI - Progression from Vegetative to Minimally Conscious State Is Associated with Changes in Brain Neural Response to Passive Tasks: A Longitudinal Single-Case Functional MRI Study. AB - OBJECTIVES: Functional magnetic resonance imaging (fMRI) may be adopted as a complementary tool for bedside observation in the disorders of consciousness (DOC). However, the diagnostic value of this technique is still debated because of the lack of accuracy in determining levels of consciousness within a single patient. Recently, Giacino and colleagues (2014) hypothesized that a longitudinal fMRI evaluation may provide a more informative assessment in the detection of residual awareness. The aim of this study was to measure the correspondence between clinically defined level of awareness and neural responses within a single DOC patient. METHODS: We used a follow-up fMRI design in combination with a passive speech-processing task. Patient's consciousness was measured through time by using the Coma Recovery Scale. RESULTS: The patient progressed from a vegetative state (VS) to a minimally conscious state (MCS). Patient's task related neural responses mirrored the clinical change from a VS to an MCS. Specifically, while in an MCS, but not a VS, the patient showed a selective recruitment of the left angular gyrus when he listened to a native speech narrative, as compared to the reverse presentation of the same stimulus. Furthermore, the patient showed an increased response in the language-related brain network and a greater deactivation in the default mode network following his progression to an MCS. CONCLUSIONS: Our findings indicate that longitudinal assessment of brain responses to passive stimuli can contribute to the definition of the clinical status in individual patients with DOC and represents an adequate counterpart of the bedside assessment during the diagnostic decision-making process. (JINS, 2016, 22, 620-630). PMID- 27264965 TI - Structural and Rotational Dynamics of Carbon Dioxide in 1-Alkyl-3 methylimidazolium Bis(trifluoromethylsulfonyl)imide Ionic Liquids: The Effect of Chain Length. AB - Ionic liquids (ILs) have been proposed as possible carbon dioxide (CO2) capture media; thus, it is useful to understand the dynamics of both the dissolved gas and its IL environment as well as how altering an IL affects these dynamics. With increasing alkyl chain length, it is well-established that ILs obtain a mesoscopic structural feature assigned to polar-apolar segregation, and the change in structure with chain length affects the dynamics. Here, the dynamics of CO2 in a series of 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ILs, in which the alkyl group is ethyl, butyl, hexyl, or decyl, were investigated using ultrafast infrared spectroscopy by measuring the reorientation and spectral diffusion of carbon dioxide in the ILs. It was found that reorientation of the carbon dioxide occurs on three time scales, which correspond to two different time scales of restricted wobbling-in-a-cone motions and a long-time complete diffusive reorientation. Complete reorientation slows with increasing chain length but less than the increases in viscosity of the bulk liquids. Spectral diffusion, measured with two-dimensional IR spectroscopy, is caused by a combination of the liquids' structural fluctuations and reorientation of the CO2. The data were analyzed using a recent theory that takes into account both contributions to spectral diffusion and extracts the structural spectral diffusion. Different components of the structural fluctuations have distinct dependences on the alkyl chain length. All of the dynamics are fast compared to the complete orientational randomization of the bulk ILs, as measured with optical heterodyne-detected optical Kerr effect measurements. The results indicate a hierarchy of constraint releases in the liquids that give rise to increasingly slower dynamics. PMID- 27264966 TI - Effect of vaccination with a modified live porcine reproductive and respiratory syndrome virus vaccine on growth performance in fattening pigs under field conditions. AB - Porcine reproductive and respiratory syndrome virus (PRRSV) has caused significant economic losses to the global swine industry. The present study aimed to evaluate the efficacy of a commercial PRRSV modified live virus (MLV) vaccine in conventionally reared growing/finishing pigs. Four barns were designated for groups A, B, C and D in the growing-to-finishing site. All pigs of the A barn were vaccinated with a commercial PRRSV MLV vaccine, whereas pigs of the B, C or D barn as control groups were unvaccinated. Twenty pigs randomly selected and tagged from each barn were serially bled at 0, 20, 40 and 60 day-post vaccination, and tested for serological response with a commercial enzyme-linked immunosorbent assay kit. Body weights were measured to calculate the average daily-weight gain (ADG). Serological assays indicated that the seropositivity of the PRRSV-vaccinated group was higher than that of the unvaccinated groups at 40 day-post-vaccination. ADG of group A was significantly higher than that of groups B and C, and the mean weights of groups A, B, C and D were 0.82 +/- 0.017, 0.76 +/- 0.016, 0.74 +/- 0.019 and 0.81 +/- 0.018 kg, respectively. In conclusion, the present study reports the serological responses and growth performance parameters by the PRRSV MLV vaccine in growing/finishing pigs under field conditions. PMID- 27264967 TI - Caring for Patients with Totally Endoscopic Coronary Artery Bypass: Special Considerations for the ED Nurse. PMID- 27264968 TI - Response to "Putting the cart before the horse: A cost effectiveness analysis of treatments for stuttering in young children requires evidence that the treatments analyzed were effective". PMID- 27264970 TI - [Motivations and emotional experiences of the first hospital multidisciplinary team trained to care for people with Ebola in Andalusia, Spain (2014-2016)]. AB - OBJECTIVE: The Hospital Universitario Virgen del Rocio (HUVR) of Seville was chosen as the reference Andalusian site to treat possible cases of Ebola. After the health alert (WHO, 2014), a voluntary group of healthcare and non-healthcare professionals was set up, which, after being trained, treated a possible case. In this light, the aim is to understand the motivations and emotional experiences of this group and to identify the facilitators of and obstacles to its operation. METHOD: Qualitative, interpretative and phenomenological study. Observation unit: professional team of the HUVR trained to treat Ebola cases. Analysis units: teamwork, motivations and emotions. Three interviews with key informants were conducted, as well as three discussion groups involving 23 of the 60 team members (2014-2016). A content analysis of the motivations, emotions and elements affecting the team's operation was conducted with QSRNUDISTVivo10. VALIDITY: data sources, techniques and disciplinary perspectives were triangulated. The results were presented to the team, which duly agreed with the findings. RESULTS: Training, professional responsibility, professional self-esteem, risk appetite or loyalty to the leader stood out as motivations to voluntarily join the team. Emotional experiences evolved from fear and stress to self-pressure control, while essential elements for the team's operation were found to be calmness and confidence based on training and teamwork. Family, source department, resources, communication media and emotional management were facilitators of or obstacles to the team's success. CONCLUSION: An understanding of the key motivational and influential factors may be important in the management of effective and successful multidisciplinary teams during health alerts. PMID- 27264969 TI - The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin specific protease-14 and induces apoptosis of multiple myeloma cells. AB - Inhibition of deubiquitinase (DUB) activity is a promising strategy for cancer therapy. VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Here we show that VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) in vitro, with comparatively weaker inhibitory activity towards UCHL5 (ubiquitin-C-terminal hydrolase-5). Exposure of multiple myeloma cells to VLX1570 resulted in thermostabilization of USP14 at therapeutically relevant concentrations. Transient knockdown of USP14 or UCHL5 expression by electroporation of siRNA reduced the viability of multiple myeloma cells. Treatment of multiple myeloma cells with VLX1570 induced the accumulation of proteasome-bound high molecular weight polyubiquitin conjugates and an apoptotic response. Sensitivity to VLX1570 was moderately affected by altered drug uptake, but was unaffected by overexpression of BCL2-family proteins or inhibitors of caspase activity. Finally, treatment with VLX1570 was found to lead to extended survival in xenograft models of multiple myeloma. Our findings demonstrate promising antiproliferative activity of VLX1570 in multiple myeloma, primarily associated with inhibition of USP14 activity. PMID- 27264971 TI - [Impact of the Core Training Law on preventive medicine and public health training and other common medical specialties]. AB - OBJECTIVE: The purpose of the Core Training Law (CTL) is to amend specialised medical training to include 24 months of common training. The aim of this study is to assess its potential impact on the Preventive Medicine and Public Health (PM&PH) training programme and other medical specialties. METHOD: The programmes of the 21 common medical specialties were analysed and the recommended training periods for each specialty collected, before the information was agreed upon by three observers. The training impact was calculated as the percentage of months that should be amended per specialty to adapt to the common training schedule. RESULTS: The Preventive Medicine and Public Health training programme is the specialty most affected by the Core Training Law (100%, 24 months). Intensive medicine (0%, 0 months) and medical oncology (17%, 4 months) is the least affected. CONCLUSIONS: The CTL affects the common medical specialties in different ways and requires a complete reorganisation of the activities and competencies of PM&PH professionals. PMID- 27264974 TI - Antithrombotic Agents in the Management of Sepsis. AB - Sepsis, a systemic inflammatory syndrome, is a response to infection and when associated with multiple organ dysfunction is termed, severe sepsis. It remains a leading cause of mortality in the critically ill. The response to the invading bacteria may be considered as a balance between proinflammatory and antiinflammatory reaction. While an inadequate proinflammatory reaction and a strong antiinflammatory response could lead to overwhelming infection and death of the patient, a strong and uncontrolled proinflammatory response, manifested by the release of proinflammatory mediators may lead to microvascular thrombosis and multiple organ failure. Endotoxin triggers sepsis by releasing various mediators including tumor necrosis factor-alpha and interleukin-1(IL-1). These cytokines activate the complement and coagulation systems, release adhesion molecules, prostaglandins, leukotrienes, reactive oxygen species and nitric oxide (NO). Other mediators involved in the sepsis syndrome include IL-1, IL-6 and IL-8; arachidonic acid metabolites; platelet activating factor (PAF); histamine; bradykinin; angiotensin; complement components and vasoactive intestinal peptide. These proinflammatory responses are counteracted by IL-10. Most of the trials targeting the different mediators of proinflammatory response have failed due a lack of correct definition of sepsis. Understanding the exact pathophysiology of the disease will enable better treatment options. Targeting the coagulation system with various anticoagulant agents including antithrombin, activated protein C (APC), tissue factor pathway inhibitor (TFPI) is a rational approach. Many clinical trials have been conducted to evaluate these agents in severe sepsis. While trials on antithrombin and TFPI were not so successful, the double blind, placebo-controlled, phase III trial of recombinant human activated protein C worldwide evaluation in severe sepsis (PROWESS) was successful, significantly decreasing mortality when compared to the placebo group. Better understanding of the pathophysiologic mechanism of severe sepsis will provide better treatment options. Combination antithrombotic therapy may provide a multipronged approach for the treatment of severe sepsis. PMID- 27264972 TI - Controlled Inhibition of the Mesenchymal Stromal Cell Pro-inflammatory Secretome via Microparticle Engineering. AB - Mesenchymal stromal cells (MSCs) are promising therapeutic candidates given their potent immunomodulatory and anti-inflammatory secretome. However, controlling the MSC secretome post-transplantation is considered a major challenge that hinders their clinical efficacy. To address this, we used a microparticle-based engineering approach to non-genetically modulate pro-inflammatory pathways in human MSCs (hMSCs) under simulated inflammatory conditions. Here we show that microparticles loaded with TPCA-1, a small-molecule NF-kappaB inhibitor, when delivered to hMSCs can attenuate secretion of pro-inflammatory factors for at least 6 days in vitro. Conditioned medium (CM) derived from TPCA-1-loaded hMSCs also showed reduced ability to attract human monocytes and prevented differentiation of human cardiac fibroblasts to myofibroblasts, compared with CM from untreated or TPCA-1-preconditioned hMSCs. Thus, we provide a broadly applicable bioengineering solution to facilitate intracellular sustained release of agents that modulate signaling. We propose that this approach could be harnessed to improve control over MSC secretome post-transplantation, especially to prevent adverse remodeling post-myocardial infarction. PMID- 27264973 TI - Sepsis Induces Hematopoietic Stem Cell Exhaustion and Myelosuppression through Distinct Contributions of TRIF and MYD88. AB - Toll-like receptor 4 (TLR4) plays a central role in host responses to bacterial infection, but the precise mechanism(s) by which its downstream signaling components coordinate the bone marrow response to sepsis is poorly understood. Using mice deficient in TLR4 downstream adapters MYD88 or TRIF, we demonstrate that both cell-autonomous and non-cell-autonomous MYD88 activation are major causes of myelosuppression during sepsis, while having a modest impact on hematopoietic stem cell (HSC) functions. In contrast, cell-intrinsic TRIF activation severely compromises HSC self-renewal without directly affecting myeloid cells. Lipopolysaccharide-induced activation of MYD88 or TRIF contributes to cell-cycle activation of HSC and induces rapid and permanent changes in transcriptional programs, as indicated by persistent downregulation of Spi1 and CebpA expression after transplantation. Thus, distinct mechanisms downstream of TLR4 signaling mediate myelosuppression and HSC exhaustion during sepsis through unique effects of MyD88 and TRIF. PMID- 27264976 TI - High Factor VIII Antigen Levels are not Associated with Factor VIII Gene Polymorphisms. PMID- 27264975 TI - Variable Expression and Hypermethylation of p16 Gene in Patients with T-ALL and Cell Lines. AB - The multi tumor suppressor genes MTS1 (CDKN2, p16INK4A) and MTS2 (CDKN1, p15INK4B) located at 9p21-22 are inactivated in some human cancers via several mechanisms including deletion and hypermethylation. In hematological malignancies, deletion of p16/p15 locus has been shown to be highly specific to lymphoid malignancies, and more particularly to T-cell acute lymphoblastic leukemia (TALL). We have investigated the deletion, methylation and p16 protein expression status of MTS1 in Tcell childhood acute lymphoblastic leukemia (19 cases) and cell lines[11]. On Southern blot homozygous deletions or hemizygous deletion with rearangement were detected in 4/19 T-ALL. The expression of p16 protein was not observed on Western blot in 4/15 T-ALL with intact p16 gene. The p16 gene was methylated 3/15 in T-ALL. Only one of three expressed p16 protein. The other 11/15 T-ALL had p16 protein expression but different level. Loss of MTS1 was observed in 3/11 cell lines. Cell line with MTS1 gene had p16 protein expression in 6/8. After treatment with the demethylating agent (5-AzoCyt) RD cell line showed p16 expression. This has not been observed with the other cell lines. Thus hypermethylation of MTS1 is rare in childhood T-ALL. Although inactivation of MTS1 by deletion is common in T-ALL and cell lines. Furthermore our data show that the p16 gene inactivation by hypermethylation and deletion may play a role in the leukemogenesis. PMID- 27264977 TI - The Role of ABO Incompatibility in Allogeneic Peripheral Blood Stem Cell Transplant. AB - ABO incompatibility is not a contraindication for allogeneic bone marrow transplantation, but this procedure requires an extra effort for erythrocyte or plasma depletion in certain well established conditions. Some acute or delayed immunohematological complications such as acute or chronic hemolysis and pure red cell aplasia may be encountered. In this study the outcome and transplant related complications of ABO incompatible and identical cases, who have received allogeneic peripheral blood stem cells from their HLA identical siblings were compared with each other. Ninety-one patients (CML 36, AML 37, other 18) were analyzed retrospectively including 51 (60.4%) ABO identical patients and 36 (39.6%) ABO mismatched (MM) patients, who have a bi-directional MM (n= 5), major MM (n= 16), minor MM (n= 9) and Rh MM (n= 6). Median follow up was 13 (0.5-43.0) months. We did not observed any significant differences between two groups (identical vs non-identical) in terms of acute hemolysis preceding stem cell infusion, peritransplant transfusion demand, acute- and chronic graft versus host disease. There was no change in estimated disease free survival and overall survival durations. We did not observed any influence of ABO/Rh incompatibility on short term outcome in allogeneic peripheral blood stem cell transplantation in our series and did not recommend further manipulation of the infused stem cells. PMID- 27264978 TI - Infantile Malignant Osteopetrosis: Delay in Diagnosis Eliminates Chance of Cure. AB - A 4.5 year-old girl presented with abdominal distention, failure to thrive, visual and hearing loss. In her medical history there was meningitis in the neonatal period, convulsions, enlargement of her head, nistagmus and exophtalmus at the tenth month. When she was 15 month-old, she had ventriculoperitoneal shunt and surgical transection of the filum terminale due to tethered cord. When she was 3 yearold she had headaches and swallowing difficulties and she underwent suboccipital craniectomi and C1 laminectomi. On admission to our Center she had normal mental and motor development, high arched palate, only three teeth, hepatosplenomegaly, weight and height below 3 percentile, leukoerythroblastic anemia and thrombocytopenia. Roentgenograms of bones showed sclerosis and no medullary tissue could be obtained in bone marrow biopsy. Diagnosis was infantile malignant osteopetrosis but the patient can not be referred to bone marrow transplantation due to delay in diagnosis and irreversible visual and hearing loss and lack of medullary space for marrow engraftment. PMID- 27264979 TI - Prolonged Partial Thromboplastin Time Without Bleeding History; Fletcher Factor Deficiency. AB - A 67-year-old patient was admitted to the hospital to perform an esophagogastrectomy because a lesion at the lower esophagus was strongly suspicious for cancer. Her medical history and her family history were negative for bleeding tendency or thrombosis. Her activated partial thromboplastin time (aPTT) was prolonged (44 s) whereas her prothrombin time (PT) was normal (11 s) presurgery. Mixing of her plasma with normal plasma corrected her prolonged aPTT (27.9 s). Prolonged incubation shortened the patient's aPTT (36.3 s). Fletcher factor activity was found to be 50%. The patient underwent an esophagogastrectomy without bleeding complications under spinal anesthesia. Fletcher factor deficiency, a rare disorder, should be considered in patients who have no history of bleeding tendency with a prolonged aPTT. Surgical interventions are safe in these patients. PMID- 27264980 TI - Extramedullary Presentation of Biclonal IgGk and IgAk Multiple Myeloma. AB - Multiple myeloma is characterized by plasma cell infiltration of the bone marrow and the presence of a monoclonal protein in the plasma or the urine in 90% of cases. Major manifestations of the disease are bone pain, anemia, renal insufficiency and recurrent infections. Less frequent presentations are hepatic and splenic enlargement (5% of cases), lymphadenopathy (4%) and biclonal gammopathy (1%). In this report we describe a biclonal multiple myeloma presenting with cervical lymphadenopathy and sternal mass. The immunohistochemical study of the lymph node and the flow cytometric analysis of the bone marrow showed IgGk and IgAk biclonality. In this report the features of lymph node involvement and biclonality constitute a rare presentation of multiple myeloma. PMID- 27264982 TI - Images in Haematology. PMID- 27264981 TI - Stevens-Johnson Syndrome-Like Exanthema Secondary to Methotrexate. AB - Methotrexate is an antineoplastic drug used commonly in leukemia treatment. Because of becoming resistant to standard doses after 1970s, it is used intermediate or high doses. The complications of high doses are mucositis, vomiting, dermatitis exfoliativa, B-cell dysfunction, hepatotoxicity, nephrotoxicity and bone marrow depression. There were only two studies in literature about Stevens-Johnson syndrome occuring in two patients with acute lymphocytic leukemia and non-Hodgkin lymphoma after receiving high doses methotrexate and leukoverin. We have reported a two-year-old boy patient suffering from acute lymphocytic leukemia (ALL) developed a severe skin reaction two days after administration of high dose methotrexate. The skin lesions simulated Stevens-Johnson syndrome with ulceration of the oral mucosa and erythema multiforme-like target lesions. PMID- 27264983 TI - The Incidence of Alpha-Thalassemia in Antalya- Turkey. PMID- 27264984 TI - Inhibition of LPS-induced inflammatory mediators by 3-hydroxyanthranilic acid in macrophages through suppression of PI3K/NF-kappaB signaling pathways. AB - Many tryptophan metabolites have immunomodulatory effects on various immune cells. 3-Hydroxyanthranilic Acid (3-HAA) is a tryptophan metabolite reported to have anti-inflammatory activity. The mechanism of this activity is unclear. The present study examined the immunomodulatory effects and molecular mechanisms of 3 HAA on macrophages. Pretreatment of 3-HAA (0.1-10 MUg mL(-1)) for 2 h markedly inhibited NO and cytokine production in LPS-stimulated Raw 264.7 cells. Moreover, translocation and activation of NF-kappaB by LPS in the nucleus were abrogated through the prevention of IkappaB degradation by 3-HAA treatment. 3-HAA significantly suppressed LPS-induced PI3K/Akt/mTOR activation, whereas MAPKs were not affected by 3-HAA treatment. Furthermore, the inhibition of mTOR by 3-HAA resulted in decreased production of inflammatory mediators and NF-kappaB activity. Similar results were also observed in primary peritoneal macrophages. Furthermore, 3-HAA modulated macrophage polarization. Collectively, the results suggest that 3-HAA has an immunomodulatory effect that may result from inhibition of PI3K/Akt/mTOR and NF-kappaB activation, thereby decreasing the production of pro-inflammatory mediators. PMID- 27264986 TI - Elevated heart rate and nondipping heart rate as potential targets for melatonin: a review. AB - Elevated heart rate is a risk factor for cardiovascular and all-cause mortalities in the general population and various cardiovascular pathologies. Insufficient heart rate decline during the night, that is, nondipping heart rate, also increases cardiovascular risk. Abnormal heart rate reflects an autonomic nervous system imbalance in terms of relative dominance of sympathetic tone. There are only a few prospective studies concerning the effect of heart rate reduction in coronary heart disease and heart failure. In hypertensive patients, retrospective analyses show no additional benefit of slowing down the heart rate by beta blockade to blood pressure reduction. Melatonin, a secretory product of the pineal gland, has several attributes, which predict melatonin to be a promising candidate in the struggle against elevated heart rate and its consequences in the hypertensive population. First, melatonin production depends on the sympathetic stimulation of the pineal gland. On the other hand, melatonin inhibits the sympathetic system in several ways representing potentially the counter regulatory mechanism to normalize excessive sympathetic drive. Second, administration of melatonin reduces heart rate in animals and humans. Third, the chronobiological action of melatonin may normalize the insufficient nocturnal decline of heart rate. Moreover, melatonin reduces the development of endothelial dysfunction and atherosclerosis, which are considered a crucial pathophysiological disorder of increased heart rate and pulsatile blood flow. The antihypertensive and antiremodeling action of melatonin along with its beneficial effects on lipid profile and insulin resistance may be of additional benefit. A clinical trial investigating melatonin actions in hypertensive patients with increased heart rate is warranted. PMID- 27264987 TI - Response to Dr. Al-Ani's letter: Klippel-Feil Syndrome associated with Pierre Robin Sequence and mandibular duplication. PMID- 27264985 TI - Out-of-Sample Extrapolation utilizing Semi-Supervised Manifold Learning (OSE SSL): Content Based Image Retrieval for Histopathology Images. AB - Content-based image retrieval (CBIR) retrieves database images most similar to the query image by (1) extracting quantitative image descriptors and (2) calculating similarity between database and query image descriptors. Recently, manifold learning (ML) has been used to perform CBIR in a low dimensional representation of the high dimensional image descriptor space to avoid the curse of dimensionality. ML schemes are computationally expensive, requiring an eigenvalue decomposition (EVD) for every new query image to learn its low dimensional representation. We present out-of-sample extrapolation utilizing semi supervised ML (OSE-SSL) to learn the low dimensional representation without recomputing the EVD for each query image. OSE-SSL incorporates semantic information, partial class label, into a ML scheme such that the low dimensional representation co-localizes semantically similar images. In the context of prostate histopathology, gland morphology is an integral component of the Gleason score which enables discrimination between prostate cancer aggressiveness. Images are represented by shape features extracted from the prostate gland. CBIR with OSE-SSL for prostate histology obtained from 58 patient studies, yielded an area under the precision recall curve (AUPRC) of 0.53 +/- 0.03 comparatively a CBIR with Principal Component Analysis (PCA) to learn a low dimensional space yielded an AUPRC of 0.44 +/- 0.01. PMID- 27264988 TI - Measurement of flying and diving metabolic rate in wild animals: Review and recommendations. AB - Animals' abilities to fly long distances and dive to profound depths fascinate earthbound researchers. Due to the difficulty of making direct measurements during flying and diving, many researchers resort to modeling so as to estimate metabolic rate during each of those activities in the wild, but those models can be inaccurate. Fortunately, the miniaturization, customization and commercialization of biologgers has allowed researchers to increasingly follow animals on their journeys, unravel some of their mysteries and test the accuracy of biomechanical models. I provide a review of the measurement of flying and diving metabolic rate in the wild, paying particular attention to mass loss, doubly-labelled water, heart rate and accelerometry. Biologgers can impact animal behavior and influence the very measurements they are designed to make, and I provide seven guidelines for the ethical use of biologgers. If biologgers are properly applied, quantification of metabolic rate across a range of species could produce robust allometric relationships that could then be generally applied. As measuring flying and diving metabolic rate in captivity is difficult, and often not directly translatable to field conditions, I suggest that applying multiple techniques in the field to reinforce one another may be a viable alternative. The coupling of multi-sensor biologgers with biomechanical modeling promises to improve precision in the measurement of flying and diving metabolic rate in wild animals. PMID- 27264990 TI - Within-subject non-concordance of abdominal v. general high adiposity: definition and analysis issues. PMID- 27264991 TI - A method for the analysis of multiple novel halogenated flame retardants in cow's milk. AB - A method was developed for the extraction and analysis of cow's milk to measure 21 halogenated flame retardants (FRs), including individual isomers plus eight methoxy-polybrominated diphenyl ethers (MeO-PBDEs). Extraction was performed using homogenisation with acetone:hexane with size exclusion chromatography followed by adsorption chromatography clean-up. Analysis was undertaken using gas chromatography high-resolution mass spectrometry. The method was validated in fortified cow's milk with FRs and 2-methoxy-PBDE 68 at three levels (low [12.5 1250 pg g(-)(1)], mid [37.5-5000 pg g(-)(1)] and high [400-10 000 pg g(-)(1)]). Additional methoxy-PBDEs were tested at two fortification levels. Isotope dilution was used to correct for losses during sample preparation and average recoveries ranged from 58% (allyl 2,4,6-tribromophenyl ether [ATE]) to 121% (gamma-tetrabromoethylcyclohexane (gamma-TBECH)). Limits of detection ranged from 0.055 pg g(-)(1) (6-methoxy-PBDE 47) to 38.9 pg g(-)(1) (decabromodiphenylethane (DBDPE)). Matrix effects were overcome through the use of surrogate and performance standards. A single FR (1-bromomethyl-2,3,4,5,6-pentabromobenzene [PBBB]) and two methoxy-PBDEs were detected in commercially available cow's milk collected from local supermarkets in Ottawa, ON, Canada. Detection frequency was < 25% for these compounds and, where present, concentrations were low. PMID- 27264992 TI - Isoxazole-Derived Amino Acids are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation into Histone H4 Peptides and Histone H3. AB - A range of isoxazole-containing amino acids was synthesized that displaced acetyl lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3. PMID- 27264994 TI - An extra dimension in protein tagging by quantifying universal proteotypic peptides using targeted proteomics. AB - The use of protein tagging to facilitate detailed characterization of target proteins has not only revolutionized cell biology, but also enabled biochemical analysis through efficient recovery of the protein complexes wherein the tagged proteins reside. The endogenous use of these tags for detailed protein characterization is widespread in lower organisms that allow for efficient homologous recombination. With the recent advances in genome engineering, tagging of endogenous proteins is now within reach for most experimental systems, including mammalian cell lines cultures. In this work, we describe the selection of peptides with ideal mass spectrometry characteristics for use in quantification of tagged proteins using targeted proteomics. We mined the proteome of the hyperthermophile Pyrococcus furiosus to obtain two peptides that are unique in the proteomes of all known model organisms (proteotypic) and allow sensitive quantification of target proteins in a complex background. By combining these 'Proteotypic peptides for Quantification by SRM' (PQS peptides) with epitope tags, we demonstrate their use in co-immunoprecipitation experiments upon transfection of protein pairs, or after introduction of these tags in the endogenous proteins through genome engineering. Endogenous protein tagging for absolute quantification provides a powerful extra dimension to protein analysis, allowing the detailed characterization of endogenous proteins. PMID- 27264993 TI - 5-Aminoimidazole-4-carboxamide ribonucleoside-mediated adenosine monophosphate activated protein kinase activation induces protective innate responses in bacterial endophthalmitis. AB - The retina is considered to be the most metabolically active tissue in the body. However, the link between energy metabolism and retinal inflammation, as incited by microbial infection such as endophthalmitis, remains unexplored. In this study, using a mouse model of Staphylococcus aureus (SA) endophthalmitis, we demonstrate that the activity (phosphorylation) of 5' adenosine monophosphate activated protein kinase alpha (AMPKalpha), a cellular energy sensor and its endogenous substrate; acetyl-CoA carboxylase is down-regulated in the SA-infected retina. Intravitreal administration of an AMPK activator, 5-aminoimidazole-4 carboxamide ribonucleoside (AICAR), restored AMPKalpha and acetyl-CoA carboxylase phosphorylation. AICAR treatment reduced both the bacterial burden and intraocular inflammation in SA-infected eyes by inhibiting NF-kB and MAP kinases (p38 and JNK) signalling. The anti-inflammatory effects of AICAR were diminished in eyes pretreated with AMPK inhibitor, Compound C. The bioenergetics (Seahorse) analysis of SA-infected microglia and bone marrow-derived macrophages revealed an increase in glycolysis, which was reinstated by AICAR treatment. AICAR also reduced the expression of SA-induced glycolytic genes, including hexokinase 2 and glucose transporter 1 in microglia, bone marrow-derived macrophages and the mouse retina. Interestingly, AICAR treatment enhanced the bacterial phagocytic and intracellular killing activities of cultured microglia, macrophages and neutrophils. Furthermore, AMPKalpha1 global knockout mice exhibited increased susceptibility towards SA endophthalmitis, as evidenced by increased inflammatory mediators and bacterial burden and reduced retinal function. Together, these findings provide the first evidence that AMPK activation promotes retinal innate defence in endophthalmitis by modulating energy metabolism and that it can be targeted therapeutically to treat ocular infections. PMID- 27264995 TI - Robust, Self-Healing Superhydrophobic Fabrics Prepared by One-Step Coating of PDMS and Octadecylamine. AB - A robust, self-healing superhydrophobic poly(ethylene terephthalate) (PET) fabric was fabricated by a convenient solution-dipping method using an easily available material system consisting of polydimethylsiloxane and octadecylamine (ODA). The surface roughness was formed by self-roughening of ODA coating on PET fibers without any lithography steps or adding any nanomaterials. The fabric coating was durable to withstand 120 cycles of laundry and 5000 cycles of abrasion without apparently changing the superhydrophobicity. More interestingly, the fabric can restore its super liquid-repellent property by 72 h at room temperature even after 20000 cycles of abrasion. Meanwhile, after being damaged chemically, the fabric can restore its superhydrophobicity automatically in 12 h at room temperature or by a short-time heating treatment. We envision that this simple but effective coating system may lead to the development of robust protective clothing for various applications. PMID- 27265003 TI - Evaluation of non-coding variation in GLUT1 deficiency. AB - AIM: Loss-of-function mutations in SLC2A1, encoding glucose transporter-1 (GLUT 1), lead to dysfunction of glucose transport across the blood-brain barrier. Ten percent of cases with hypoglycorrhachia (fasting cerebrospinal fluid [CSF] glucose <2.2mmol/L) do not have mutations. We hypothesized that GLUT1 deficiency could be due to non-coding SLC2A1 variants. METHOD: We performed whole exome sequencing of one proband with a GLUT1 phenotype and hypoglycorrhachia negative for SLC2A1 sequencing and copy number variants. We studied a further 55 patients with different epilepsies and low CSF glucose who did not have exonic mutations or copy number variants. We sequenced non-coding promoter and intronic regions. We performed mRNA studies for the recurrent intronic variant. RESULTS: The proband had a de novo splice site mutation five base pairs from the intron-exon boundary. Three of 55 patients had deep intronic SLC2A1 variants, including a recurrent variant in two. The recurrent variant produced less SLC2A1 mRNA transcript. INTERPRETATION: Fasting CSF glucose levels show an age-dependent correlation, which makes the definition of hypoglycorrhachia challenging. Low CSF glucose levels may be associated with pathogenic SLC2A1 mutations including deep intronic SLC2A1 variants. Extending genetic screening to non-coding regions will enable diagnosis of more patients with GLUT1 deficiency, allowing implementation of the ketogenic diet to improve outcomes. PMID- 27265004 TI - Fatty acids determination in Bronte pistachios by gas chromatographic method. AB - A gas chromatographic with flame ionization detector (GC-MS FID) method for the identification and quantification of fatty acids based on the extraction of lipids and derivatisation of free acids to form methyl esters was developed and validated. The proposed method was evaluated to a number of standard FAs, and Bronte pistachios samples were used for that purpose and to demonstrate the applicability of the proposed method. In this regard, repeatability, mean and standard deviation of the analytical procedure were calculated. The results obtained have demonstrated oleic acid as the main component of Bronte pistachios (72.2%) followed by linoleic acid (13.4%) and showed some differences in composition with respect to Tunisian, Turkish and Iranian pistachios. PMID- 27265005 TI - How Clinically Relevant Are Treatment Comparisons of Topical Calcineurin Inhibitor Trials for Atopic Eczema? AB - We sought to explore the architecture of trials of calcineurin inhibitors for atopic eczema to document the extent to which comparisons with active treatments such as topical corticosteroids might have been included or avoided. We identified all eligible randomized controlled trials using the Global Resource for EczemA Trials (GREAT) database. Network plots were produced where the nodes represented a treatment type and the lines between the nodes represented the number of trials or participants involved in the various treatment comparisons. A total of 174 randomized controlled trials for atopic eczema treatments were identified in which pimecrolimus, tacrolimus, or topical corticosteroids were compared with another intervention or a vehicle/emollient. Of 39 trials involving pimecrolimus and 41 trials involving tacrolimus, 8 (20.5%) and 13 (31.7%), respectively, made comparisons with topical corticosteroids, and 25 (64.1%) and 15 (36.6%), respectively, were vehicle-controlled studies. The high rate of comparisons with vehicle controls in randomized controlled trials that assessed the efficacy of pimecrolimus or tacrolimus long after efficacy had been established is a matter of concern. Active comparators (mild topical corticosteroids for pimecrolimus and moderate to potent topical corticosteroids for tacrolimus) are best placed to determine how topical calcineurin inhibitors compare with established clinical practice. PMID- 27265007 TI - Imatinib mesylate and the management of chronic myeloid leukemia (CML). PMID- 27265006 TI - Low Levels of Genetic Heterogeneity in Matched Lymph Node Metastases from Patients with Melanoma. PMID- 27265008 TI - Factor V A4070G (His1299Arg) mutation in Turkish pediatric patients with thrombosis. AB - The role of the prothrombotic mutations in pediatric thrombosis are being investigated. Mutations in the factor V gene (FV G1691A and FV A4070G) leading to activated protein C resistance, the main pathological condition in thrombosis and prothrombotic mutations contributing to thrombosis have been identified. The aim of this study is to reveal the role of FV A4070G mutation in pediatric thrombosis. 314 patients with thrombosis at pediatric age including also 111 stroke patients and 127 healthy controls were included to the study. The FV A4070G mutation was evaluated independently and also the combined effects with other prothrombotic mutations were also investigated. In pediatric stroke group FV A4070G was found not to be a risk factor with an OR of 1.04 (CI 95%: 0.56 1.93, p= 0.884). Further studies are needed to study the role of FV A4070G with other risk factors belong to HR2 haplotype. PMID- 27265009 TI - Body mass index, fibrinogen and factor VII activity in male smokers and non smokers living in an Urban industrialized. AB - Differences in haemostatic parameters have been reported among smokers and non smokers. However the relationships of these parameters with other risk factors of cardiovascular diseases have not been fully determined in Nigerians. We therefore aimed at assessing the relationship between fibrinogen, factor VII (FVII), age, body mass indeks (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in smokers and non-smokers living in an Urban Nigerian city. We studied 104 male Nigerians grouped into non-smokers (n= 74) and smokers (n= 30). Fibrinogen was measured using the clot weight method of Ingram and FVII was assayed by the bioassay method. Mean fibrinogen and FVII were found to be higher in smokers than non-smokers. There was no relationship between FVII and age (r= 0.0458) in non-smokers and a weak association was found between FVII and age in smokers (r= 0.3191). Both SBP and DBP were significantly associated with BMI in smokers (r= 0.6332, p= 0.0002) for DBP and (r= 0.4869, p= 0.0064) for SBP. Fibrinogen was only associated with DBP in non-smokers (r= 0.3273, p= 0.0047). FVII and fibrinogen were found to be higher in smokers compared to non- smokers, the difference was not statistically significant (p= 0.1965). The strength of the association of BMI and fibrinogen with blood pressure is higher for DBP in Nigerians. Extensive population studies should be conducted on smokers and non smokers to confirm these associations. PMID- 27265010 TI - Effects of high-dose methylprednisolone therapy on lymphocyte subtypes in patients with acute immune thrombocytopenic purpura. AB - The aim of this study was to determine the effect of high-dose methylprednisolone (HDMP) on lymphocyte subtypes, CD4/CD8 ratio and clinical efficacy of the treatment in children with acute immune thrombocytopenic purpura (ITP). The study consisted of 21 children (aged between 1.5-14 years) with ITP treated with HDMP for 7 days. Absolute lymphocyte count, CD4+ and CD8+ T lymphocyte levels were examined on peripheral blood and CD4/CD8 ratio was calculated before and after HMTP treatment (on 0 and 8th days) in all subjects. There was no statistically significant difference for age and sex between the study and the control group. A significant reduction was observed in the percentage of CD4+ lymphocyte (39.0 +/- 7.5% vs 29.3 +/- 8.1%, p= 0.001), CD8+ lymphocyte (27.1 +/- 7.2% vs 23.7 +/- 8.3%, p= 0.03), CD4+/CD8+ (1.5 +/- 0.5 vs 1.3 +/- 0.4, p= 0.02) and the absolute number of CD4+ lymphocyte count (1694.99 +/- 1019 vs 1199.12 +/- 612, p= 0.038). These findings indicated that HDMP treatment may cause a decrease in the percentage of CD4+ and CD8+ T-lymphocyte and ratio of CD4+/CD8+ lymphocyte in patients with acute ITP. We suggest that the effectiveness of steroids may depended upon the suppression of CD4 T-lymphocyte and sequential monitoring of circulating lymphocyte subtypes may be used to predict the clinical effects of steroid treatment. PMID- 27265011 TI - Interleukin-10 and interferon-gamma cytokine gene polymorphisms may be risk factors for chronic myelogenous leukemia. AB - We investigated the association of cytokine gene polymorphisms with the development of chronic myelogenous leukemia (CML) and whether there is an association between gene polymorphisms Th1 and Th2 or regulatory- type cytokines and CML. Thirty patients with CML and 60 healthy controls were enrolled in this study. All genotyping (TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma) studies were performed using sequence-specific primers PCR (PCR-SSP). Frequencies of IL 10 (-1082, -819, -592) GCC/ATA (p= 0.009) and IFN-gamma; +874 T/A (p= 0.037) polymorphisms were significantly greater in the patients with CML. In contrast, significantly lower frequencies of the IFN-gamma A/A (p= 0.004) genotype were observed in patients with CML compared with controls. The results suggest that the IL-10 GCC/ATA and IFN-gamma T/A polymorphisms are potential risk factors, and that the IFN-gamma A/A polymorphism is a protective factor, for CML in this study group. PMID- 27265012 TI - Posttransplant lymphoma in renal and heart allograft recipients: a single center experience. AB - Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% to 32%. Herein we retrospectively analyzed the patients who diagnosed as PTLD in Akdeniz University. Within the 782 (773 renal and 9 heart) transplant recipients six patients were diagnosed as PTLD (diffuse large B-cell lymphoma). Five of them had renal, one had cardiac transplantation. Three patients were diagnosed within the first year of transplantation. Five patients had abdominal disease one had central nervous system involvement. All patients had positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) IgG at the time of diagnose. EBV-DNA with polymerase chain reaction (PCR) was found to be negative in five patients. Only one patient was survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate is high in patients with PTLD. In order to decrease the incidence of PTLD and related mortality, the risk factors should be evaluated with multicenter studies. PMID- 27265013 TI - Rapid progression of acquired amegakaryocytic thrombocytopenia to myelodysplastic syndrome: case report. AB - Acquired amegakaryocytic thrombocytopenia (AAT) is a rare disease characterized by severe thrombocytopenia due to selective reduction or absence of megakaryocytes in the bone marrow. More commonly, patients with AAT have additional hematologic abnormalities such as macrocytosis or dyserythropoiesis, abnormalities which may predict progression to aplastic anemia or myelodysplasia. A 52-year-old female was admitted to hospital with mucosal and gingival bleeding. Megakaryocytes were not seen on the bone marrow aspiration and biopsy. AAT was diagnosed. Although she was treated with immunosuppressive therapy including prednisolone and cyclosporine, her disease progressed to myelodysplastic syndrome. She died at the third month of diagnosis because of cerebral bleeding. PMID- 27265014 TI - High-dose steroid-related osteonecrosis in a four-year-old child with acute lymphoblastic leukemia. AB - Osteonecrosis is an uncommon complication of acute lymphoblastic leukemia. One of the risk factor is high-dose corticosteroid therapy. The highest incidence of osteonecrosis is observed in children 9 to 18 years old at diagnosis and it is a rare condition below 5 years of age. We describe a 4 year-old child with acute lymphoblastic leukemia and complaints of progressive bone pain and walking difficulty who developed osteonecrosis and bone fracture after two remission induction chemotherapy. PMID- 27265015 TI - Images in Hematology. PMID- 27265016 TI - Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals. AB - Oxidative stress is a well-known pathogenic mechanism of a diverse array of neurological diseases, and thus, numerous studies have attempted to identify antioxidants that prevent neuronal cell death. GV1001 is a 16-amino-acid peptide derived from human telomerase reverse transcriptase (hTERT). Considering that hTERT has a strong antioxidant effect, whether GV1001 also has an antioxidant effect is a question of interest. In the present study, we aimed to investigate the effects of GV1001 against oxidative stress in neural stem cells (NSCs). Primary culture NSCs were treated with different concentrations of GV1001 and/or hydrogen peroxide (H2O2) for various time durations. The H2O2 decreased the viability of the NSCs in a concentration-dependent manner, with 200MUM H2O2 significantly decreasing both proliferation and migration. However, treatment with GV1001 rescued the viability, proliferation and migration of H2O2-injured NSCs. Consistently, free radical levels were increased in rat NSCs treated with H2O2, while co-treatment with GV1001 significantly reduced these levels, especially the intracellular levels. In addition, GV1001 restored the expression of survival-related proteins and reduced the expression of death-associated ones in NSCs treated with H2O2. In conclusion, GV1001 has antioxidant and neuroprotective effects in NSCs following treatment with H2O2, which appear to be mediated by scavenging free radicals, increasing survival signals and decreasing death signals. PMID- 27265018 TI - Corrigendum to "Desmethylanhydroicaritin isolated from Sophora flavescens, shows antitumor activities in U87MG cells via inhibiting the proliferation, migration and invasion" [Environ. Toxicol. Pharmacol. 43 (2016) 140-148]. PMID- 27265017 TI - Long-term exposure to ambient air pollution and incidence of brain tumours: The Danish Nurse Cohort. AB - BACKGROUND: Air pollution has been considered a potent environmental risk factor for neuropathology through neuroinflammation and oxidative stress, which might also cause brain tumour formation. However, epidemiological evidence on the association between air pollution and brain tumours in humans is sparse, with no data on exposure to particles. In this study we aim to examine associations between long-term exposure to ambient air pollution and risk for development of brain tumours. METHODS: We used the Danish Nurse Cohort with 28,731 female nurses (age>=44years) recruited in 1993 or 1999 when self-reported information on lifestyle was collected. We obtained data on the incidence of brain tumours until 2013 from the Danish Cancer Register, and estimated annual mean concentrations of particulate matter with diameter<2.5MUm (PM2.5), particulate matter with diameter<10MUm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2) at the residence since 1990 using an atmospheric integrated chemistry-transport models system, and examined the association between the 3-year running mean of pollutants and brain tumour incidence using time-varying Cox regression, separately for total brain tumours, and for tumour subtypes by location (brain or meninges), and by malignancy (malignant or benign), and estimated hazard ratios and 95% confidence intervals per increase in interquartile range of exposure. RESULTS: Of 25,143 tumour-free nurses at recruitment, 121 developed brain cancer during 15.7 years of follow-up. We found a weak positive association between total brain tumours and PM2.5 (1.06; 0.80-1.40 per 3.37MUg/m(3)), NO2 (1.09; 0.91 1.29) per 7.5MUg/m(3), and NOx (1.02; 0.93-1.12 per 10.22MUg/m(3)), and none with PM10 (0.93; 0.70-1.23 per 3.31MUg/m(3)). Associations with PM2.5 and NO2 were stronger for tumours located in meninges than in brain, and for benign than for malignant tumours. Finally, association of total brain tumours with PM2.5 was modified by BMI, and was statistically significantly enhanced in obese women (2.03; 1.35-3.05). CONCLUSION: We found weak evidence for association between risk of brain tumours and long-term exposure to air pollution in women older than 44 years. However, we present novel results that obese women may be susceptible, as well as a positive tendency towards elevated risk for meninges and benign tumours, which require further investigation. PMID- 27265019 TI - Single-Electron Transmetalation: Photoredox/Nickel Dual Catalytic Cross-Coupling of Secondary Alkyl beta-Trifluoroboratoketones and -esters with Aryl Bromides. AB - The first cross-coupling of secondary alkyl beta-trifluoroboratoketones and esters has been achieved through application of photoredox/nickel dual catalysis. Although the related beta-trifluoroboratoamides have been effectively cross coupled via Pd-catalysis, the corresponding ketones and esters had proven recalcitrant prior to this report. Reactions occur under mild conditions, and a variety of functional groups and sterically and electronically diverse reaction partners are tolerated. PMID- 27265020 TI - Probing the interaction of U(vi) with phosphonate-functionalized mesoporous silica using solid-state NMR spectroscopy. AB - The fundamental interaction of U(vi) with diethylphosphatoethyl triethoxysilane functionalized SBA-15 mesoporous silica is studied by macroscopic batch experiments and solid-state NMR spectroscopy. DPTS-functionalized silica has been shown to extract U(vi) from nitric acid solutions at or above pH 3. Extraction is dependent on pH and ionic strength. Single-pulse (31)P NMR on U(vi) contacted samples revealed that U(vi) only interacts with a fraction of the ligands present on the surface. At pH 4 the U(vi) extraction capacity of the material is limited to 27-37% of the theoretical capacity, based on ligand loading. We combined single pulse (31)P NMR on U(vi)-contacted samples with batch studies to measure a ligand-to-metal ratio of approximately 2 : 1 at pH 3 and 4. Batch studies and cross-polarization NMR measurements reveal that U(vi) binds to deprotonated phosphonate and/or silanol sites. We use (31)P-(31)P DQ-DRENAR NMR studies to compare the average dipolar coupling between phosphorus spins for both U(vi) complexed and non-complexed ligand environments. These measurements reveal that U(vi) extraction is not limited by inadequate surface distribution of ligands, but rather by low stability of the surface phosphonate complex. PMID- 27265021 TI - Involvement of the Hippocampus in Binge Ethanol-Induced Spleen Atrophy in Adolescent Rats. AB - BACKGROUND: Ethanol (EtOH) affects the immune system. Binge drinking of hard liquor initiates a stress response. This form of drinking is popular during adolescence, which involves maturation of the immune system. The spleen is a key immune organ, and spleen atrophy is associated with immunosuppression. While the hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the initial stress response, the hippocampus may be involved in stress beyond the HPA axis. METHODS: Blood ethanol concentration (BEC), blood endotoxin levels, and plasma corticosterone levels were measured following binge EtOH treatment. Absolute and relative spleen sizes were analyzed, and stress-related gene expression was compared in the hypothalamus and hippocampus. Polymerase chain reaction array was performed to analyze the expression profile of EtOH metabolism and immune regulation-related genes in the spleen. Relationships among variables were analyzed using the Pearson correlation. RESULTS: At 24 hours following a 3-day EtOH treatment, no significant difference in BEC was detected between EtOH treated and control rats. Average plasma endotoxin levels in EtOH-treated animals were significantly higher than in controls, and spleen size was significantly lower. Spleen size did not correlate with plasma endotoxin levels; however, it did significantly negatively correlate with plasma corticosterone levels. Spleen size significantly negatively correlated with hippocampal CRH expression and significantly positively correlated with hippocampal MR expression. No correlation was observed in the hypothalamus. Significantly higher hippocampal CRH and significantly lower MR expression was seen in low spleen/body weight (sp wt) ratio rats. No gene was found to decrease expression >=1.5-fold (p < 0.05) in the spleen of high sp-wt group, whereas expression of several genes, including Gabra1, Gabra5, Ifnb1, Irf9, Il12b, and Cx3cr1, decreased significantly in the low sp-wt group. CONCLUSIONS: Our findings suggest that binge EtOH exposure causes lower spleen size in adolescents and that the hippocampus and stress may be associated with alterations in spleen structure and gene expression. PMID- 27265022 TI - Chemical quenching of singlet oxygen by betanin. AB - Betanin is the best known natural dye belonging to the betacyanin family. In this work, efficient singlet oxygen quenching by betanin in deuterated water with the rate constant 1.20 +/- 0.15 * 10(8) M(-1) s(-1) is reported, deduced from the (1)O2 phosphorescence decays measured as a function of betanin concentration. The quenching occurs by a chemical mechanism, as confirmed by the analysis of the transient absorption kinetics at the probe lambda ~ 535 nm, by comparison of the initial triplet signal amplitude of perinaphthenone acting as the (1)O2 photosensitizer with the final bleaching signal of betanin. The main betanin oxidation product is 2-decarboxy-2,3-dehydrobetanin, with its formation observed as the transient absorption signal at lambda ~ 445 nm. LC-MS/MS analysis of the photolyzed solutions supports the product identification as 2-decarboxy-2,3 dehydrobetanin, based on the molecular ion [M](+) observed at m/z 505. Isobetanin also undergoes a similar photooxidation reaction. PMID- 27265025 TI - Coiling ultrathin tellurium nanowires into nanorings by Pickering emulsion. AB - Well-defined hydrophilic ultrathin tellurium nanowires (TeNWs) can be coiled into nanorings by Pickering emulsion at room temperature. PMID- 27265023 TI - Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion. AB - B cells play a central role in antibody-mediated rejection and certain autoimmune diseases. However, B cell-targeted therapy such as anti-CD20 B cell-depleting antibody (aCD20) has yielded mixed results in improving outcomes. In this study, we investigated whether an accelerated B cell reconstitution leading to aCD20 depletion resistance could account for these discrepancies. Using a transplantation model, we found that antigen-independent inflammation, likely through toll-like receptor (TLR) signaling, was sufficient to mitigate B cell depletion. Secondary lymphoid organs had a quicker recovery of B cells when compared to peripheral blood. Inflammation altered the pharmacokinetics (PK) and pharmacodynamics (PD) of aCD20 therapy by shortening drug half-life and accelerating the reconstitution of the peripheral B cell pool by bone marrow derived B cell precursors. IVIG (intravenous immunoglobulin) coadministration also shortened aCD20 drug half-life and led to accelerated B cell recovery. Repeated aCD20 dosing restored B cell depletion and delayed allograft rejection, especially B cell-dependent, antibody-independent allograft rejection. These data demonstrate the importance of further clinical studies of the PK/PD of monoclonal antibody treatment in inflammatory conditions. The data also highlight the disconnect between B cell depletion on peripheral blood compared to secondary lymphoid organs, the deleterious effect of IVIG when given with aCD20 and the relevance of redosing of aCD20 for effective B cell depletion in alloimmunity. PMID- 27265024 TI - Incidence and long-term outcome of postradiotherapy moyamoya syndrome in pediatric patients with primary brain tumors: a single institute experience in Taiwan. AB - We aimed to investigate the incidence and long-term outcome of moyamoya syndrome in pediatric patients with primary brain tumors after receiving cranial radiotherapy (RT) in a single institute in Taiwan. The complete medical records, medical images, and RT notes of 391 pediatric patients with primary brain tumors treated with cranial RT between January 1975 and December 2005 in Taipei Veterans General Hospital (TVGH), Taiwan, were entered into an electronic registry and reviewed. Eight (2%) cases of post-RT moyamoya syndrome were identified in the sample of 391 patients. The median latency was 3 years post-RT. Among the eight patients, three had craniopharyngioma, two had optic glioma, two had medulloblastoma, and one had a suprasellar astrocytoma. The prescribed physical doses of RT were in the range of 40-54 Gy. The incidence was highest in those with optic glioma (0.039/person-year), followed by craniopharyngioma (0.013/person-year), astrocytoma (0.003/person-year), and medulloblastoma (0.002/person-year). No patients died of vasculopathy. No difference in crude incidence was found between our results and those of other series. The incidence of moyamoya syndrome was diagnosis dependent, with the highest incidence among patients with optic glioma. No regional difference in incidence was found. Long term, stable neurological function may be achieved following timely surgical intervention. PMID- 27265026 TI - Development of a niobium-doped titania inert anode for titanium electrowinning in molten chloride salts. AB - The direct electrochemical reduction of solid titanium dioxide in a chloride melt is an attractive method for the production of titanium metal. It has been estimated that this type of electrolytic approach may reduce the costs of producing titanium sponge by more than half, with the additional benefit of a smaller environmental footprint. The process utilises a consumable carbon anode which releases a mixture of CO2 and CO gas during electrolysis, but suffers from low current efficiency due to the occurrence of parasitic side reactions involving carbon. The replacement of the carbon anode with a cheap, robust inert anode offers numerous benefits that include: elimination of carbon dioxide emissions, more efficient cell operation, opportunity for three-dimensional electrode configurations and reduced electrode costs. This paper reports a study of Nb-doped titania anode materials for inert anodes in a titanium electrolytic reduction cell. The study examines the effect of niobium content and sintering conditions on the performance of Nb-doped TiO2 anodes in laboratory-scale electrolysis tests. Experimental findings, including performance in a 100 h laboratory electrolysis test, are described. PMID- 27265027 TI - Correlation between the acid-base properties of the La2O3 catalyst and its methane reactivity. AB - Density functional theory and coupled cluster theory calculations were carried out to study the effects of the acid-base properties of the La2O3 catalyst on its catalytic activity in the oxidative coupling of methane (OCM) reaction. The La(3+)-O(2-) pair site for CH4 activation is considered as a Lewis acid-Bronsted base pair. Using the Lewis acidity and the Bronsted basicity in the fluoride affinity and proton affinity scales as quantitative measures of the acid-base properties, the energy barrier for CH4 activation at the pair site can be linearly correlated with these acid-base properties. The pair site consisting of a strong Lewis acid La(3+) site and a strong Bronsted base O(2-) site is the most reactive for CH4 activation. In addition, the basicity of the La2O3 catalyst was traditionally measured by temperature-programmed desorption of CO2, but the CO2 chemisorption energy is better regarded as a combined measure of the acid-base properties of the pair site. A linear relationship of superior quality was found between the energy barrier for CH4 activation and the CO2 chemisorption energy, and the pair site favorable for CO2 chemisorption is also more reactive for CH4 activation, leading to the conflicting role of the "basicity" of the La2O3 catalyst in the OCM reaction. The necessity for very high reaction temperatures in the OCM reaction is rationalized by the requirement for the recovery of the most reactive acid-base pair site, which unfortunately also reacts most readily with the byproduct CO2 to form the very stable CO3(2-) species. PMID- 27265028 TI - Transcriptome analysis of genes related to resistance against powdery mildew in wheat-Thinopyrum alien addition disomic line germplasm SN6306. AB - Wheat powdery mildew, which is mainly caused by Blumeria graminis f. sp. tritici (Bgt), seriously damages wheat production. The wheat-Thinopyrum intermedium alien addition disomic line germplasm SN6306, being one of the important sources of genes for wheat resistance, is highly resistant to Bgt E09 and to many other powdery mildew physiological races. However, knowledge on the resistance mechanism of SN6306 remains limited. Our study employed high-throughput RNA sequencing based on next-generation sequencing technology (Illumina) to obtain an overview of the transcriptome characteristics of SN6306 and its parent wheat Yannong 15 (YN15) during Bgt infection. The sequencing generated 104,773 unigenes, 9909 of which showed varied expression levels. Among the 9909 unigenes, 1678 unigenes showed 0 reads in YN15. The expression levels in Bgt-inoculated SN6306 and YN15 of exactly 39 unigenes that showed 0 or considerably low reads in YN15 were validated to identify the genes involved in Bgt resistance. Among the 39 unigenes, 12 unigenes were upregulated in SN6306 by 3-45 times. These unigenes mainly encoded kinase, synthase, proteases, and signal transduction proteins, which may play an important role in the resistance against Bgt. To confirm whether the unigenes that showed 0 reads in YN15 are really unique to SN6306, 8 unigenes were cloned and sequenced. Results showed that the selected unigenes are more similar to SN6306 and Th. intermedium than to the wheat cultivar YN15. The sequencing results further confirmed that the unigenes showing 0 reads in YN15 are unique to SN6306 and are most likely derived from Th. intermedium (Host) Nevski. Thus, the genes from Th. intermedium most probably conferred the resistance of SN6306 to Bgt. PMID- 27265029 TI - Aberrant methylation of ATG2B, ATG4D, ATG9A and ATG9B CpG island promoter is associated with decreased mRNA expression in sporadic breast carcinoma. AB - Epigenetic modifications are critical determinants in tumor initiation and progression. This study aims to detect the promoter methylation status and the mRNA expression levels of ATG2B, ATG4D, ATG9A and ATG9B, and then to explore their relationship in invasive ductal carcinomas (IDCs) and matched normal tissues (MNTs) of the breast. Methylation was observed as follows: 61.0% in ATG2B, 46.8% in ATG4D, 56.4% in ATG9A, and 74.0% in ATG9B of IDCs. Meanwhile, their mRNA expression levels of the IDCs was lower than that of the MNTs (P<0.001, P=0.019, P<0.001 and P<0.001, respectively). Methylated IDCs of ATG2B, ATG9A, ATG9B and unmethylated ATG4D, ATG9B showed significantly lower expression values compared to the MNTs (P=0.003, P<0.001, P<0.001, P=0.014 and P=0.002, respectively). The methylations of ATG2B and ATG9B were related to their lower expression levels in IDCs (P=0.017 and P=0.023). Moreover, ATG2B methylation was positively associated with the grade (P=0.024) and TNM stage (P=0.015); Methylation of ATG4D and ATG9A was positively correlated to lymph node involvement (P=0.012 and P=0.018), while methylation of ATG9B appeared susceptible to CK5/6 positive status and deteriorated TNM stages (P=0.003 and P=0.012). Moreover, the decreased expression of ATG2B was related to the ER and PR status (P=0.004 and P=0.003). The ER, HER-2 and lymph node metastasis status are the determinants to reducing the expression of ATG4D, ATG9A and ATG9B (P=0.026, P=0.010 and P=0.011, respectively). This study highlights the transcriptional inactivation mechanisms of ATG2B, ATG4D, ATG9A and ATG9B promoter methylation status and the possible origin of autophagy signal pathway repression in IDCs. PMID- 27265030 TI - A global study of transcriptome dynamics in canola (Brassica napus L.) responsive to Sclerotinia sclerotiorum infection using RNA-Seq. AB - The necrotrophic phytopathogen, Sclerotinia sclerotiorum, causes Sclerotinia stem rot, which is a serious constraint to canola (Brassica napus L.) production worldwide. To understand the detailed molecular mechanisms underlying host response to Sclerotinia infection, we analyzed the transcript level changes in canola post-infection with S. sclerotiorum in a time course of a compatible interaction using strand specific whole transcriptome sequencing. Following infection, 161 and 52 genes (P<=0.001) were induced while 24 and 23 genes were repressed at 24h post-inoculation (hpi) and 48hpi, respectively. This suggests that, a gradual increase in host cell lyses and increase virulence of the pathogen led to the expression of only a fewer host specific genes at the later stage of infection. We observed rapid induction of key pathogen responsive genes, including glucanases, chitinases, peroxidases and WRKY Transcription factors (TFs) within 24hpi, indicating early detection of the pathogen by the host. Only 16 genes were significantly induced at both the time points suggesting a coordinated suppression of host responses by the pathogen. In addition to genes involved in plant-pathogen interactions, many novel disease responsive genes, including various TF sand those associated with jasmonate (JA) and ethylene (ET) signalling were identified. This suggests that canola adopts multiple strategies in mediating plant responses to the pathogen attack. Quantitative real time PCR (qRT-PCR) validation of a selected set of genes demonstrated a similar trend as observed by RNA-Seq analysis and highlighted the potential involvement of these genes by the host to defend itself from pathogen attack. Overall, this work presents an in-depth analysis of the interaction between host susceptibility and pathogen virulence in the agriculturally important B. napus-S. sclerotiorum pathosystem. PMID- 27265031 TI - Nucleopolyhedroviruses (NPV) induce the expression of small heat shock protein 25.4 in Antheraea pernyi. AB - Nucleopolyhedroviruses (NPVs) is one group of Baculoviruses. The infection of NPV in silkworm is often lethal. To investigate the effective measures to stop the infection of NPV, we cloned cDNA encoding small heat shock protein 25.4 in Antheraea pernyi (Ap-HSP25.4). The translated amino acid sequence consisted of 223 residues with a calculated molecular mass of 25.4kDa and an isoelectronic point (pI) of 4.93. Quantitative real-time PCR was used to investigate the expression patterns and distribution profiles of Ap-sHSP25.4 before and after challenged with NPV. We found that the inhibitors of eicosanoid synthesis could suppress the transcription of Ap-sHSP25.4 in the fat body in a dose dependent manner. And arachidonic acid induced the expression of Ap-sHSP25.4. Thus, we concluded that sHSPs may be promising candidates to boost insect immunity in practice. PMID- 27265032 TI - Network analysis of genes and their association with diseases. AB - A plethora of network-based approaches within the Systems Biology universe have been applied, to date, to investigate the underlying molecular mechanisms of various human diseases. In the present study, we perform a bipartite, topological and clustering graph analysis in order to gain a better understanding of the relationships between human genetic diseases and the relationships between the genes that are implicated in them. For this purpose, disease-disease and gene gene networks were constructed from combined gene-disease association networks. The latter, were created by collecting and integrating data from three diverse resources, each one with different content covering from rare monogenic disorders to common complex diseases. This data pluralism enabled us to uncover important associations between diseases with unrelated phenotypic manifestations but with common genetic origin. For our analysis, the topological attributes and the functional implications of the individual networks were taken into account and are shortly discussed. We believe that some observations of this study could advance our understanding regarding the etiology of a disease with distinct pathological manifestations, and simultaneously provide the springboard for the development of preventive and therapeutic strategies and its underlying genetic mechanisms. PMID- 27265034 TI - Thinking ahead: Executive dysfunction in bipolar disorder. PMID- 27265035 TI - Interactions of Oryza sativa OsCONTINUOUS VASCULAR RING-LIKE 1 (OsCOLE1) and OsCOLE1-INTERACTING PROTEIN reveal a novel intracellular auxin transport mechanism. AB - Little is known about the transport mechanism of intracellular auxin. Here, we report two vacuole-localized proteins, Oryza sativa OsCONTINUOUS VASCULAR RING LIKE 1 (OsCOLE1) and OsCOLE1-INTERACTING PROTEIN (OsCLIP), that regulate intracellular auxin transport and homoeostasis. Overexpression of OsCOLE1 markedly increased the internode length and auxin content of the stem base, whereas these parameters were decreased in RNA interference (RNAi) plants. OsCOLE1 was localized on the tonoplast and preferentially expressed in mature tissues. We further identified its interacting protein OsCLIP, which was co localized on the tonoplast. Protein-protein binding assays demonstrated that the N-terminus of OsCOLE1 directly interacted with OsCLIP in yeast cells and the rice protoplast. Furthermore, (3) H-indole-3-acetic acid ((3) H-IAA) transport assays revealed that OsCLIP transported IAA into yeast cells, which was promoted by OsCOLE1. The results indicate that OsCOLE1 affects rice development by regulating intracellular auxin transport through interaction with OsCLIP, which provides a new insight into the regulatory mechanism of intracellular transport of auxin and the roles of vacuoles in plant development. PMID- 27265033 TI - Catalytic Reductive ortho-C-H Silylation of Phenols with Traceless, Versatile Acetal Directing Groups and Synthetic Applications of Dioxasilines. AB - A new, highly selective, bond functionalization strategy, achieved via relay of two transition metal catalysts and the use of traceless acetal directing groups, has been employed to provide facile formation of C-Si bonds and concomitant functionalization of a silicon group in a single vessel. Specifically, this approach involves the relay of Ir-catalyzed hydrosilylation of inexpensive and readily available phenyl acetates, exploiting disubstituted silyl synthons to afford silyl acetals and Rh-catalyzed ortho-C-H silylation to provide dioxasilines. A subsequent nucleophilic addition to silicon removes the acetal directing groups and directly provides unmasked phenol products and, thus, useful functional groups at silicon achieved in a single vessel. This traceless acetal directing group strategy for catalytic ortho-C-H silylation of phenols was also successfully applied to preparation of multisubstituted arenes. Remarkably, a new formal alpha-chloroacetyl directing group has been developed that allows catalytic reductive C-H silylation of sterically hindered phenols. In particular, this new method permits access to highly versatile and nicely differentiated 1,2,3-trisubstituted arenes that are difficult to access by other catalytic routes. In addition, the resulting dioxasilines can serve as chromatographically stable halosilane equivalents, which allow not only removal of acetal directing groups but also introduce useful functional groups leading to silicon-bridged biaryls. We demonstrated that this catalytic C-H bond silylation strategy has powerful synthetic potential by creating direct applications of dioxasilines to other important transformations, examples of which include aryne chemistry, Au catalyzed direct arylation, sequential orthogonal cross-couplings, and late-stage silylation of phenolic bioactive molecules and BINOL scaffolds. PMID- 27265036 TI - Potential impact of application of Z0011 derived criteria to omit axillary lymph node dissection in node positive breast cancer patients. AB - BACKGROUND: The ACOSOG Z0011 trial, a randomized controlled trial among patients with sentinel node positive breast cancer treated with breast conserving therapy, concluded that axillary lymph node dissection (ALND) can be omitted in these patients. However, questions were raised on the general applicability if the results of the Z0011 trial. Therefore, the aim of this study was to assess the practice changing effect of the Z0011 trial by quantifying the proportion of all node positive breast cancer patients who meet the inclusion criteria which are based on the Z0011 trial, thus in whom an ALND could be omitted. METHODS: A multicenter population based study including patients with clinical T1-2N0-1M0 invasive non-metastatic breast cancer, a positive sentinel node or ultrasound guided lymph node biopsy, treated with breast conserving therapy and adjuvant systemic therapy between January 2007 and December 2012. RESULTS: A total of 11,031 patients had invasive breast cancer including 3051 cases treated with breast conserving therapy and adjuvant systemic therapy. Subsequently, 916 cases with a positive nodal status underwent an ALND of whom 558 cases (60.9%), representing 5.1% of the total breast cancer population, would potentially have fulfilled the Z0011 criteria. CONCLUSION: Application of Z0011 based criteria is practice changing in nearly 61% of all node positive patients, which could result in omission of the ALND in a substantial number of patients in the future. Further research has to be performed on the applicability of these conclusions to other categories of breast cancer patients. PMID- 27265037 TI - Systematic review and meta-analysis of the complications of salvage total laryngectomy. AB - BACKGROUND AND OBJECTIVES: Management paradigms in laryngeal cancer have shifted to "organ preservation" chemoradiotherapy protocols. In the event of treatment failure, salvage total laryngectomy remains the only curative treatment option. However a comprehensive review of the complications of this procedure has not been reported. METHODS: A systematic review of the literature was performed using keywords "salvage laryngectomy" to retrieve relevant publications between January 2000 and August 2015. RESULTS: Of the 407 articles retrieved from the literature search, 50 studies encompassing 3292 patients were included. Forty-nine studies reported pharyngocutaneous fistula which occurred in 859 patients (pooled incidence 28.9%; 95% confidence intervals 25.5-32.5%). Twenty-four studies reported complications in addition to PCF and these included wound complications (infection, dehiscence and necrosis), dysphagia, bleeding, and pharyngeal and stomal stenosis. CONCLUSIONS: Overall complication rate was 67.5%, Pharyngocutaneous fistula was the commonest complication with a pooled incidence of 28.9%. PMID- 27265038 TI - Comparing a thyroid prognostic nomogram to the existing staging systems for prediction risk of death from thyroid cancers. AB - OBJECTIVE: Thyroid prognostic nomogram can be applied across different histological types for predicting the individualized risk of death from thyroid cancer. The objective of this study was to compare the strength of our recently published thyroid prognostic nomogram with 12 existing staging systems to predict the risk of death from thyroid cancer. METHOD: This study included 1900 thyroid cancer patients, from a population based cohort of 2296 patients, on whom adequate staging information was available. Competing risk sub-hazard models were used to compare 12 pre-existing prognostic models with the nomogram model. Their relative strengths for prediction of patients' individualized risks of death from thyroid cancer were compared using Akaike information criterion (AIC), delta AIC, and concordance index. R version 3.2.2 was used to analyze the data. RESULTS: Our cohort of 450 males and 1450 females included 1796 (93.4%) differentiated thyroid cancers. Amongst the compared models, thyroid prognostic nomogram model appeared to be better than other models for predicting the risk of death from all non anaplastic thyroid cancer (concordance index = 94.4), differentiated thyroid cancer (concordance index = 94.1) and papillary thyroid cancer (concordance index = 94.7). The difference from next best staging systems was most pronounced in non anaplastic thyroid cancer (delta AIC = 114.8), followed by differentiated thyroid cancer (delta AIC = 35.6) and papillary thyroid cancer (delta AIC = 8.4). CONCLUSIONS: Thyroid prognostic nomogram model was found to be better than the other models compared for predicting risk of death from thyroid cancer. PMID- 27265039 TI - Anesthesia and colorectal cancer - The perioperative period as a window of opportunity? AB - Gastrointestinal malignancies largely contribute to cancer related deaths in the United States, with colorectal cancer representing the 3rd place of the ten leading entities of mortality due to cancer for both females and males. The majority of patients with GI tumors has to undergo surgery (either as a curative or palliative intervention) and are therefore also in need for a proper general and/or regional anesthesia. Recent findings have suggested that the type of anesthesia administered might have an impact on cancer recurrence and metastasis and thus this new field in the anesthesia world has become a largely studied topic. This review highlights current concepts and summarizes the evidence for an impact of the type of anesthesia on patient outcome after cancer surgery, suggesting the perioperative period might be a "window of opportunity" which should not be missed. PMID- 27265040 TI - Gastric GISTs: Analysis of c-Kit, PDGFRA and BRAF mutations in relation to prognosis and clinical pathological characteristics of patients - A GIRCG study. AB - BACKGROUND: Gastric gastrointestinal stromal tumors (GISTs) represent a subgroup of GISTs with a better prognosis than those located in other areas. In this retrospective study we performed a molecular characterization of a large series of patients with gastric GISTs in relation to clinical-pathological characteristics and prognosis. METHODS: DNA was extracted from paraffin-embedded sections from 221 gastric GIST patients submitted to surgery. Exons 9, 11, 13 and 17 of KIT, exons 12 and 18 of PDGFRA and exons 11 and 15 of BRAF were analyzed by direct sequencing. Cox regression analysis adjusted for clinical-pathological factors was performed to evaluate KIT and PDGFRA mutations in relation to the composite endpoint of relapse or death. RESULTS: KIT and PDGFRA mutations were observed in 119 (53.8%) and 56 (25.3%) patients, respectively, whereas 46 (20.8%) patients had wild type (wt) disease. Univariable analyses showed that a high Miettinen risk category and the presence of ulceration and KIT deletions were associated with increased risk of relapse or death (p < 0.001; p = 0.0389 and p = 0.002, respectively). After adjusting for Miettinen risk score, KIT deletions remained an independent prognostic factor (HRadj = 2.65, 95% CI [1.15-6.13], p = 0.023). Moreover, KIT deletions in exon 11 codons 557, 558 or 559 were associated with a higher risk of relapse or death than wt tumors (HRadj = 3.29 95% CI [1.64 6.64], p = 0.001). CONCLUSIONS: KIT deletions in exon 11, especially those involving codons 557, 558 or 559, were correlated with a more aggressive gastric GIST phenotype and increased risk of relapse or death. PMID- 27265041 TI - Current and future role of circulating tumor cells in patients with epithelial ovarian cancer. AB - Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy". PMID- 27265042 TI - Fat grafting for breast cancer patients: From basic science to clinical studies. AB - Fat grafting in the surgical treatment of breast cancer has become popular in a short period of time because of the rising expectations of good esthetic results by the patients as well as the simplicity of the technique; however, the oncological safety for breast cancer patients remains a matter of debate. The procedure raises many questions considering that recent in-vitro studies have shown that fat grafting could promote tumor recurrence through diverse mechanisms, or even facilitate distant metastasis. We present a review of the currently available experimental and clinical data in order to describe and discuss patient selection criteria following breast cancer surgery. PMID- 27265043 TI - Interactive breast mass segmentation using a convex active contour model with optimal threshold values. AB - INTRODUCTION: A convex active contour model requires a predefined threshold value to determine the global solution for the best contour to use when doing mass segmentation. Fixed thresholds or manual tuning of threshold values for optimum mass boundary delineation are impracticable. A proposed method is presented to determine an optimized mass-specific threshold value for the convex active contour derived from the probability matrix of the mass with the particle swarm optimization method. We compared our results with the Chan-Vese segmentation and a published global segmentation model on masses detected on direct digital mammograms. METHODS AND MATERIALS: The regional term of the convex active contour model maximizes the posterior partitioning probability for binary segmentation. Suppose the probability matrix is binary thresholded using the particle swarm optimization to obtain a value T1, we define the optimal threshold value for the global minimizer of the convex active contour as the mean intensity of all pixels whose probabilities are greater than T1. RESULTS: The mean Jaccard similarity indices were 0.89+/-0.07 for the proposed/Chan-Vese method and 0.88+/-0.06 for the proposed/published segmentation model. The mean Euclidean distance between Fourier descriptors of the segmented areas was 0.05+/-0.03 for the proposed/Chan Vese method and 0.06+/-0.04 for the proposed/published segmentation model. CONCLUSIONS: This efficient method avoids problems of initial level set contour placement and contour re-initialization. Moreover, optimum segmentation results are realized for all masses improving on the fixed threshold value of 0.5 proposed elsewhere. PMID- 27265044 TI - A graphical user interface (GUI) toolkit for the calculation of three-dimensional (3D) multi-phase biological effective dose (BED) distributions including statistical analyses. AB - A toolkit has been developed for calculating the 3-dimensional biological effective dose (BED) distributions in multi-phase, external beam radiotherapy treatments such as those applied in liver stereotactic body radiation therapy (SBRT) and in multi-prescription treatments. This toolkit also provides a wide range of statistical results related to dose and BED distributions. MATLAB 2010a, version 7.10 was used to create this GUI toolkit. The input data consist of the dose distribution matrices, organ contour coordinates, and treatment planning parameters from the treatment planning system (TPS). The toolkit has the capability of calculating the multi-phase BED distributions using different formulas (denoted as true and approximate). Following the calculations of the BED distributions, the dose and BED distributions can be viewed in different projections (e.g. coronal, sagittal and transverse). The different elements of this toolkit are presented and the important steps for the execution of its calculations are illustrated. The toolkit is applied on brain, head & neck and prostate cancer patients, who received primary and boost phases in order to demonstrate its capability in calculating BED distributions, as well as measuring the inaccuracy and imprecision of the approximate BED distributions. Finally, the clinical situations in which the use of the present toolkit would have a significant clinical impact are indicated. PMID- 27265045 TI - Numerical simulations of the 10-year-old head response in drop impacts and compression tests. AB - BACKGROUND AND OBJECTIVE: Studies on traumatic injuries of children indicate that impact to the head is a major cause of severe injury and high mortality. However, regulatory and ethical concerns very much limit development and validation of computer models representing the pediatric head. The purpose of this study was to develop a child head finite element model with high-biofidelity to be used for studying pediatric head injury mechanisms. METHODS: A newly developed 10-year-old (YO) pediatric finite element head model was limitedly validated for kinematic and kinetic responses against data from quasi-static compressions and drop tests obtained from an experimental study involving a child-cadaver specimen. The validated model was subsequently used for a fall accident reconstruction and associated injury analysis. RESULTS: The model predicted the same shape of acceleration-time histories as was found in drop tests with the largest discrepancy of -8.2% in the peak acceleration at a drop height of 15 cm. Force deflection responses predicted by the model for compression loading had a maximum discrepancy of 7.5% at a strain rate of 0.3 s(-1). The model-predicted maximum von Mises stress (sigmav) and principal strain (epsilonp) in the skull, intracranial pressure (ICP), maximum sigmav and maximum epsilonp in the brain, head injury criterion (HIC), brain injury criterion (BrIC), and head impact power (HIP) were used for analyzing risks of injury in the accident reconstruction. CONCLUSIONS: Based on the results of the injury analyses, the following conclusions can be drawn: (1) ICP cannot be used to accurately predict the locations of brain injury, but it may reflect the overall energy level of the impact event. (2) The brain regions predicted by the model to have high sigmav coincide with the locations of subdural hematoma with transtentorial herniation and the impact position of an actual injury. (3) The brain regions with high epsilonp predicted by the model coincide with locations commonly found where diffuse axonal injuries (DAI) due to blunt-impact and rapid acceleration have taken place. PMID- 27265046 TI - GPU-accelerated iterative reconstruction from Compton scattered data using a matched pair of conic projector and backprojector. AB - BACKGROUND AND OBJECTIVE: Iterative reconstruction from Compton scattered data is known to be computationally more challenging than that from conventional line projection based emission data in that the gamma rays that undergo Compton scattering are modeled as conic projections rather than line projections. In conventional tomographic reconstruction, to parallelize the projection and backprojection operations using the graphics processing unit (GPU), approximated methods that use an unmatched pair of ray-tracing forward projector and voxel driven backprojector have been widely used. In this work, we propose a new GPU accelerated method for Compton camera reconstruction which is more accurate by using exactly matched pair of projector and backprojector. METHODS: To calculate conic forward projection, we first sample the cone surface into conic rays and accumulate the intersecting chord lengths of the conic rays passing through voxels using a fast ray-tracing method (RTM). For conic backprojection, to obtain the true adjoint of the conic forward projection, while retaining the computational efficiency of the GPU, we use a voxel-driven RTM which is essentially the same as the standard RTM used for the conic forward projector. RESULTS: Our simulation results show that, while the new method is about 3 times slower than the approximated method, it is still about 16 times faster than the CPU-based method without any loss of accuracy. CONCLUSIONS: The net conclusion is that our proposed method is guaranteed to retain the reconstruction accuracy regardless of the number of iterations by providing a perfectly matched projector backprojector pair, which makes iterative reconstruction methods for Compton imaging faster and more accurate. PMID- 27265047 TI - A predictive mechanical model for evaluating vertebral fracture probability in lumbar spine under different osteoporotic drug therapies. AB - Osteoporotic vertebral fractures represent a major cause of disability, loss of quality of life and even mortality among the elderly population. Decisions on drug therapy are based on the assessment of risk factors for fracture from bone mineral density (BMD) measurements. A previously developed model, based on the Damage and Fracture Mechanics, was applied for the evaluation of the mechanical magnitudes involved in the fracture process from clinical BMD measurements. BMD evolution in untreated patients and in patients with seven different treatments was analyzed from clinical studies in order to compare the variation in the risk of fracture. The predictive model was applied in a finite element simulation of the whole lumbar spine, obtaining detailed maps of damage and fracture probability, identifying high-risk local zones at vertebral body. For every vertebra, strontium ranelate exhibits the highest decrease, whereas minimum decrease is achieved with oral ibandronate. All the treatments manifest similar trends for every vertebra. Conversely, for the natural BMD evolution, as bone stiffness decreases, the mechanical damage and fracture probability show a significant increase (as it occurs in the natural history of BMD). Vertebral walls and external areas of vertebral end plates are the zones at greatest risk, in coincidence with the typical locations of osteoporotic fractures, characterized by a vertebral crushing due to the collapse of vertebral walls. This methodology could be applied for an individual patient, in order to obtain the trends corresponding to different treatments, in identifying at-risk individuals in early stages of osteoporosis and might be helpful for treatment decisions. PMID- 27265048 TI - Determination of an optimal control strategy for drug administration in tumor treatment using multi-objective optimization differential evolution. AB - The mathematical modeling of physical and biologic systems represents an interesting alternative to study the behavior of these phenomena. In this context, the development of mathematical models to simulate the dynamic behavior of tumors is configured as an important theme in the current days. Among the advantages resulting from using these models is their application to optimization and inverse problem approaches. Traditionally, the formulated Optimal Control Problem (OCP) has the objective of minimizing the size of tumor cells by the end of the treatment. In this case an important aspect is not considered, namely, the optimal concentrations of drugs may affect the patients' health significantly. In this sense, the present work has the objective of obtaining an optimal protocol for drug administration to patients with cancer, through the minimization of both the cancerous cells concentration and the prescribed drug concentration. The resolution of this multi-objective problem is obtained through the Multi objective Optimization Differential Evolution (MODE) algorithm. The Pareto's Curve obtained supplies a set of optimal protocols from which an optimal strategy for drug administration can be chosen, according to a given criterion. PMID- 27265049 TI - BIOMedical Search Engine Framework: Lightweight and customized implementation of domain-specific biomedical search engines. AB - BACKGROUND AND OBJECTIVES: Text mining and semantic analysis approaches can be applied to the construction of biomedical domain-specific search engines and provide an attractive alternative to create personalized and enhanced search experiences. Therefore, this work introduces the new open-source BIOMedical Search Engine Framework for the fast and lightweight development of domain specific search engines. The rationale behind this framework is to incorporate core features typically available in search engine frameworks with flexible and extensible technologies to retrieve biomedical documents, annotate meaningful domain concepts, and develop highly customized Web search interfaces. METHODS: The BIOMedical Search Engine Framework integrates taggers for major biomedical concepts, such as diseases, drugs, genes, proteins, compounds and organisms, and enables the use of domain-specific controlled vocabulary. Technologies from the Typesafe Reactive Platform, the AngularJS JavaScript framework and the Bootstrap HTML/CSS framework support the customization of the domain-oriented search application. Moreover, the RESTful API of the BIOMedical Search Engine Framework allows the integration of the search engine into existing systems or a complete web interface personalization. RESULTS: The construction of the Smart Drug Search is described as proof-of-concept of the BIOMedical Search Engine Framework. This public search engine catalogs scientific literature about antimicrobial resistance, microbial virulence and topics alike. The keyword-based queries of the users are transformed into concepts and search results are presented and ranked accordingly. The semantic graph view portraits all the concepts found in the results, and the researcher may look into the relevance of different concepts, the strength of direct relations, and non-trivial, indirect relations. The number of occurrences of the concept shows its importance to the query, and the frequency of concept co-occurrence is indicative of biological relations meaningful to that particular scope of research. Conversely, indirect concept associations, i.e. concepts related by other intermediary concepts, can be useful to integrate information from different studies and look into non-trivial relations. CONCLUSIONS: The BIOMedical Search Engine Framework supports the development of domain-specific search engines. The key strengths of the framework are modularity and extensibilityin terms of software design, the use of open source consolidated Web technologies, and the ability to integrate any number of biomedical text mining tools and information resources. Currently, the Smart Drug Search keeps over 1,186,000 documents, containing more than 11,854,000 annotations for 77,200 different concepts. The Smart Drug Search is publicly accessible at http://sing.ei.uvigo.es/sds/. The BIOMedical Search Engine Framework is freely available for non-commercial use at https://github.com/agjacome/biomsef. PMID- 27265050 TI - Simulation study of PET detector configuration with thick light guide and GAPD array having large-area microcells for high effective quantum efficiency. AB - BACKGROUND AND OBJECTIVES: Light sharing PET detector configuration coupled with thick light guide and Geiger-mode avalanche photodiode (GAPD) with large-area microcells was proposed to overcome the energy non-linearity problem and to obtain high light collection efficiency (LCE). METHODS: A Monte-Carlo simulation was conducted for the three types of LSO block, 4 * 4 array of 3 * 3 * 20 mm(3) discrete crystals, 6 * 6 array of 2 * 2 * 20 mm(3) discrete crystals, and 12 * 12 array of 1 * 1 * 20 mm(3) discrete crystals, to investigate the scintillation light distribution after conversion of the gamma-rays in LSO. The incident photons were read out by three types of 4 * 4 array photosensors, which were PSPMT of 25% quantum efficiency (QE), GAPD1 with 50 * 50 um(2) microcells of 30% photon detection efficiency (PDE) and GAPD2 with 100 * 100 um(2) of 45% PDE. The number of counted photons in each photosensor was analytically calculated. The LCE, linearity and flood histogram were examined for each PET detector module having 99 different configurations as a function of light guide thickness ranging from 0 to 10 mm. RESULTS: The performance of PET detector modules based on GAPDs was considerably improved by using the thick light guide. The LCE was increased from 24 to 30% and from 14 to 41%, and the linearity was also improved from 0.97 to 0.99 and from 0.75 to 0.99, for GAPD1 and GAPD2, respectively. As expected, the performance of PSPMT based detector did not change. The flood histogram of 12 * 12 array PET detector modules using 3 mm light guide coupled with GAPDs was obtained by simulation, and all crystals of 1 * 1 * 20 mm(3) size were clearly identified. PET detector module coupled with thick light guide and GAPD array with large-area microcells was proposed to obtain high QE and high spatial resolution, and its feasibility was verified. CONCLUSIONS: This study demonstrated that the overall PET performance of the proposed design was considerably improved, and this approach will provide opportunities to develop GAPD based PET detector with a high LCE. PMID- 27265052 TI - Multidimensional scaling analysis of virus diseases. AB - BACKGROUND AND OBJECTIVE: Viruses are infectious agents that replicate inside organisms and reveal a plethora of distinct characteristics. Viral infections spread in many ways, but often have devastating consequences and represent a huge danger for public health. It is important to design statistical and computational techniques capable of handling the available data and highlighting the most important features. METHODS: This paper reviews the quantitative and qualitative behaviour of 22 infectious diseases caused by viruses. The information is compared and visualized by means of the multidimensional scaling technique. RESULTS: The results are robust to uncertainties in the data and revealed to be consistent with clinical practice. CONCLUSIONS: The paper shows that the proposed methodology may represent a solid mathematical tool to tackle a larger number of virus and additional information about these infectious agents. PMID- 27265051 TI - Validity of an ankle joint motion and position sense measurement system and its application in healthy subjects and patients with ankle sprain. AB - BACKGROUND AND OBJECTIVE: Ankle motion and proprioception in multiple axis movements are crucial for daily activities. However, few studies have developed and used a multiple axis system for measuring ankle motion and proprioception. This study was designed to validate a novel ankle haptic interface system that measures the ankle range of motion (ROM) and joint position sense in multiple plane movements, investigating the proprioception deficits during joint position sense tasks for patients with ankle instability. METHODS: Eleven healthy adults (mean +/- standard deviation; age, 24.7 +/- 1.9 years) and thirteen patients with ankle instability were recruited in this study. All subjects were asked to perform tests to evaluate the validity of the ankle ROM measurements and underwent tests for validating the joint position sense measurements conducted during multiple axis movements of the ankle joint. Pearson correlation was used for validating the angular position measurements obtained using the developed system; the independent t test was used to investigate the differences in joint position sense task performance for people with or without ankle instability. RESULTS: The ROM measurements of the device were linearly correlated with the criterion standards (r = 0.99). The ankle instability and healthy groups were significantly different in direction, absolute, and variable errors of plantar flexion, dorsiflexion, inversion, and eversion (p < 0.05). CONCLUSIONS: The results demonstrate that the novel ankle joint motion and position sense measurement system is valid and can be used for measuring the ankle ROM and joint position sense in multiple planes and indicate proprioception deficits for people with ankle instability. PMID- 27265053 TI - A comprehensive identification-evidence based alternative for HIV/AIDS treatment with HAART in the healthcare industries. AB - BACKGROUND AND OBJECTIVE: The HIV/AIDS-related issue has given rise to a priority concern in which potential new therapies are increasingly highlighted to lessen the negative impact of highly active anti-retroviral therapy (HAART) in the healthcare industry. With the motivation of "medical applications," this study focuses on the main advanced feature selection techniques and classification approaches that reflect a new architecture, and a trial to build a hybrid model for interested parties. METHODS: This study first uses an integrated linear nonlinear feature selection technique to identify the determinants influencing HAART medication and utilizes organizations of different condition-attributes to generate a hybrid model based on a rough set classifier to study evolving HIV/AIDS research in order to improve classification performance. RESULTS: The proposed model makes use of a real data set from Taiwan's specialist medical center. The experimental results show that the proposed model yields a satisfactory result that is superior to the listed methods, and the core condition-attributes PVL, CD4, Code, Age, Year, PLT, and Sex were identified in the HIV/AIDS data set. In addition, the decision rule set created can be referenced as a knowledge-based healthcare service system as the best of evidence based practices in the workflow of current clinical diagnosis. CONCLUSIONS: This study highlights the importance of these key factors and provides the rationale that the proposed model is an effective alternative to analyzing sustained HAART medication in follow-up studies of HIV/AIDS treatment in practice. PMID- 27265054 TI - Computational methods for the image segmentation of pigmented skin lesions: A review. AB - BACKGROUND AND OBJECTIVES: Because skin cancer affects millions of people worldwide, computational methods for the segmentation of pigmented skin lesions in images have been developed in order to assist dermatologists in their diagnosis. This paper aims to present a review of the current methods, and outline a comparative analysis with regards to several of the fundamental steps of image processing, such as image acquisition, pre-processing and segmentation. METHODS: Techniques that have been proposed to achieve these tasks were identified and reviewed. As to the image segmentation task, the techniques were classified according to their principle. RESULTS: The techniques employed in each step are explained, and their strengths and weaknesses are identified. In addition, several of the reviewed techniques are applied to macroscopic and dermoscopy images in order to exemplify their results. CONCLUSIONS: The image segmentation of skin lesions has been addressed successfully in many studies; however, there is a demand for new methodologies in order to improve the efficiency. PMID- 27265055 TI - The study of wear behaviors on abducted hip joint prostheses by an alternate finite element approach. AB - An acetabular cup with larger abduction angles is able to affect the normal function of the cup seriously that may cause early failure of the total hip replacement (THR). Complexity of the finite element (FE) simulation in the wear analysis of the THR is usually concerned with the contact status, the computational effort, and the possible divergence of results, which become more difficult on THRs with larger cup abduction angles. In the study, we propose a FE approach with contact transformation that offers less computational effort. Related procedures, such as Lagrangian Multiplier, partitioned matrix inversion, detection of contact forces, continuity of contact surface, nodal area estimation, etc. are explained in this report. Through the transformed methodology, the computer round-off error is tremendously reduced and the embedded repetitive procedure can be processed precisely and quickly. Here, wear behaviors of THR with various abduction angles are investigated. The most commonly used combination, i.e., metal-on-polyethylene, is adopted in the current study where a cobalt-chromium femoral head is paired with an Ultra High Molecular Weight Polyethylene (UHMWPE) cup. In all illustrations, wear coefficients are estimated by self-averaging strategy with available experimental datum reported elsewhere. The results reveal that the THR with larger abduction angles may produce deeper depth of wear but the volume of wear presents an opposite tendency; these results are comparable with clinical and experimental reports. The current approach can be widely applied easily to fields such as the study of the wear behaviors on ante-version, impingement, and time-dependent behaviors of prostheses etc. PMID- 27265056 TI - Application of the relative wavelet energy to heart rate independent detection of atrial fibrillation. AB - BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a growing healthcare burden worldwide. It is often asymptomatic and may appear as episodes of very short duration; hence, the development of methods for its automatic detection is a challenging requirement to achieve early diagnosis and treatment strategies. The present work introduces a novel method exploiting the relative wavelet energy (RWE) to automatically detect AF episodes of a wide variety in length. METHODS: The proposed method analyzes the atrial activity of the surface electrocardiogram (ECG), i.e., the TQ interval, thus being independent on the ventricular activity. To improve its performance under noisy recordings, signal averaging techniques were applied. The method's performance has been tested with synthesized recordings under different AF variable conditions, such as the heart rate, its variability, the atrial activity amplitude or the presence of noise. Next, the method was tested with real ECG recordings. RESULTS: Results proved that the RWE provided a robust automatic detection of AF under wide ranges of heart rates, atrial activity amplitudes as well as noisy recordings. Moreover, the method's detection delay proved to be shorter than most of previous works. A trade-off between detection delay and noise robustness was reached by averaging 15 TQ intervals. Under these conditions, AF was detected in less than 7 beats, with an accuracy higher than 90%, which is comparable to previous works. CONCLUSIONS: Unlike most of previous works, which were mainly based on quantifying the irregular ventricular response during AF, the proposed metric presents two major advantages. First, it can perform successfully even under heart rates with no variability. Second, it consists of a single metric, thus turning its clinical interpretation and real time implementation easier than previous methods requiring combined indices under complex classifiers. PMID- 27265057 TI - Influences of slip and Cu-blood nanofluid in a physiological study of cilia. AB - OBJECTIVE: The objective of this paper is to study the influences of slip and Cu blood nanofluid in a physiological study of cilia. DESIGN/METHODOLOGY/APPROACH: The right wall and the left wall possess metachronal wave that is traveling along the outer boundary of the channel. The features of ciliary structures are determined by the dominance of viscous effects over inertial effects using the long wavelength approximation. The flow possessions for the viscous nano fluid are solved as a function of the cilia and metachronal wave velocity. Mathematica numerical simulation is used to calculate pressure rise. Exact solutions are calculated for the temperature and for the velocity profile. FINDINGS: Numerical integration has been implemented to get the expression of pressure rise. Graphical results have been offered for pressure rise, temperature and stream function for various physical parameters of interest. Symmetry of the curved channel is recovered for larger values of the curvature parameter. It is found from the graphs of the pressure rise that reflux case occurs for increasing values of curvature and velocity slip parameter. It is also found that temperature decreases for increasing values of nanoparticle volume fraction. Basically, higher thermal conductivity of the nanoparticles plays a key role for quick heat dissipation, and this justifies the use of the copper nanoparticles in different situations as a coolant. CONCLUSIONS: Velocity graph near the right wall of the channel decreases when we add nanoparticles into our base fluid, whereas an opposite behavior is depicted near the left wall due to ciliated tips. Pressure gradient increases for increasing values of Gr (Grashof number), L (velocity slip parameter) phi (nanoparticle volume fraction) and k (curvature parameter). Pressure rise shows increasing behavior for the increasing values of epsilon, Gr and phi throughout the region. Shear stress graphs show the increasing behavior for increasing values of curvature parameter and volume fraction of the nanoparticle. Temperature profile decreases when we add nanoparticles into our base fluid. Temperature profile also increases with an increase in thermal slip parameter gamma and heat absorption parameter. It is observed that the number of trapped bolus increases when we increase the value of the cilia length parameter. PMID- 27265058 TI - Leveraging user's performance in reporting patient safety events by utilizing text prediction in narrative data entry. AB - BACKGROUND: Narrative data entry pervades computerized health information systems and serves as a key component in collecting patient-related information in electronic health records and patient safety event reporting systems. The quality and efficiency of clinical data entry are critical in arriving at an optimal diagnosis and treatment. The application of text prediction holds potential for enhancing human performance of data entry in reporting patient safety events. OBJECTIVE: This study examined two functions of text prediction intended for increasing efficiency and data quality of text data entry reporting patient safety events. METHODS: The study employed a two-group randomized design with 52 nurses. The nurses were randomly assigned into a treatment group or a control group with a task of reporting five patient fall cases in Chinese using a web based test system, with or without the prediction functions. T-test, Chi-square and linear regression model were applied to evaluating the outcome differences in free-text data entry between the groups. RESULTS: While both groups of participants exhibited a good capacity for accomplishing the assigned task of reporting patient falls, the results from the treatment group showed an overall increase of 70.5% in text generation rate, an increase of 34.1% in reporting comprehensiveness score and a reduction of 14.5% in the non-adherence of the comment fields. The treatment group also showed an increasing text generation rate over time, whereas no such an effect was observed in the control group. CONCLUSION: As an attempt investigating the effectiveness of text prediction functions in reporting patient safety events, the study findings proved an effective strategy for assisting reporters in generating complementary free text when reporting a patient safety event. The application of the strategy may be effective in other clinical areas when free text entries are required. PMID- 27265059 TI - A MapReduce approach to diminish imbalance parameters for big deoxyribonucleic acid dataset. AB - BACKGROUND: In the age of information superhighway, big data play a significant role in information processing, extractions, retrieving and management. In computational biology, the continuous challenge is to manage the biological data. Data mining techniques are sometimes imperfect for new space and time requirements. Thus, it is critical to process massive amounts of data to retrieve knowledge. The existing software and automated tools to handle big data sets are not sufficient. As a result, an expandable mining technique that enfolds the large storage and processing capability of distributed or parallel processing platforms is essential. METHOD: In this analysis, a contemporary distributed clustering methodology for imbalance data reduction using k-nearest neighbor (K NN) classification approach has been introduced. The pivotal objective of this work is to illustrate real training data sets with reduced amount of elements or instances. These reduced amounts of data sets will ensure faster data classification and standard storage management with less sensitivity. However, general data reduction methods cannot manage very big data sets. To minimize these difficulties, a MapReduce-oriented framework is designed using various clusters of automated contents, comprising multiple algorithmic approaches. RESULTS: To test the proposed approach, a real DNA (deoxyribonucleic acid) dataset that consists of 90 million pairs has been used. The proposed model reduces the imbalance data sets from large-scale data sets without loss of its accuracy. CONCLUSIONS: The obtained results depict that MapReduce based K-NN classifier provided accurate results for big data of DNA. PMID- 27265060 TI - Editorial. PMID- 27265061 TI - Detection of TP53/PIK3CA Mutations in Cell-Free Plasma DNA From Metastatic Breast Cancer Patients Using Next Generation Sequencing. AB - BACKGROUND: Circulating tumor DNA (ctDNA) within a liquid biopsy is a promising marker for genotyping metastatic tumors. MATERIALS AND METHODS: We performed next generation whole exon sequencing of TP53 and PIK3CA genes, which are the 2 most common genetic alterations in breast cancer, in plasma DNA (pDNA) of 17 metastatic breast cancer (MBC) patients and in tumor DNA (tDNA) from their primary tumors. RESULTS: We identified 11 mutations (6 in TP53 and 5 in PIK3CA) in tDNA from 8 patients (47%) and 13 mutations (6 in TP53 and 7 in PIK3CA) in pDNA from 7 patients (41%). Six mutations in pDNA were also identified in tDNA but seven were not. Six MBC patients with TP53 and/or PIK3CA mutations in pDNA had a significantly worse survival rate (P < .05) after recurrence than that of the other 8 MBC patients without these mutations. Carcinoembryonic antigen and cancer antigen 15-3 levels did not correlate with prognosis (P = .675 and P = .877, respectively). CONCLUSION: These results suggest that mutations in ctDNA can be detected with next generation sequencing in MBC patients and could be a more useful prognostic factor for survival after recurrence than conventional tumor markers. PMID- 27265062 TI - A systematic review of review articles addressing factors related to physical activity participation among children and adults with physical disabilities. AB - Dozens of published papers cite factors related to leisure-time physical activity (LTPA) participation among people with physical disabilities. Unfortunately, there has been little effort to synthesise this literature in a manner that is accessible and useful to the sectors (e.g., health care, recreation) responsible for LTPA promotion in disability populations. In this systematic review, over 200 factors were extracted from 22 review articles addressing barriers and facilitators to LTPA in children and adults with physical disabilities. Factors were grouped according to common themes, classified into five levels of a social ecological model, and coded according to whether they could be affected by the health-care and/or recreation sectors. Findings are discussed with regard to key factors to target in LTPA-enhancing interventions, relevant theories and models in which to frame interventions, the levels at which the interventions can be implemented, and intervention priorities. The synthesis provides a blueprint and a catalyst for researchers and practitioners to shift focus from conducting studies that merely describe LTPA barriers and facilitators, to developing and delivering strategies to increase LTPA among persons with physical disabilities. PMID- 27265063 TI - Joint state and parameter estimation of the hemodynamic model by particle smoother expectation maximization method. AB - OBJECTIVE: In this paper, we aimed for the robust estimation of the parameters and states of the hemodynamic model by using blood oxygen level dependent signal. APPROACH: In the fMRI literature, there are only a few successful methods that are able to make a joint estimation of the states and parameters of the hemodynamic model. In this paper, we implemented a maximum likelihood based method called the particle smoother expectation maximization (PSEM) algorithm for the joint state and parameter estimation. MAIN RESULTS: Former sequential Monte Carlo methods were only reliable in the hemodynamic state estimates. They were claimed to outperform the local linearization (LL) filter and the extended Kalman filter (EKF). The PSEM algorithm is compared with the most successful method called square-root cubature Kalman smoother (SCKS) for both state and parameter estimation. SCKS was found to be better than the dynamic expectation maximization (DEM) algorithm, which was shown to be a better estimator than EKF, LL and particle filters. SIGNIFICANCE: PSEM was more accurate than SCKS for both the state and the parameter estimation. Hence, PSEM seems to be the most accurate method for the system identification and state estimation for the hemodynamic model inversion literature. This paper do not compare its results with Tikhonov regularized Newton-CKF (TNF-CKF), a recent robust method which works in filtering sense. PMID- 27265064 TI - Cigarette smoking and health-promoting behaviours among tuberculosis patients in rural areas. AB - AIMS AND OBJECTIVES: To explore cigarette smoking and health-promoting behaviours among disadvantaged adults before their tuberculosis diagnosis and after their tuberculosis treatment. BACKGROUND: Although tuberculosis infection is associated with impaired immune function, healthy lifestyle habits can play a role in improving the immune system. However, limited research has explored the health promoting behaviours and cigarette smoking habits among tuberculosis patients in Taiwan. DESIGN: A cross-sectional retrospective study with a convenience sample. METHODS: This study was conducted between May 2013-June 2014 with 123 patients at a rural district hospital in Chiayi County, Taiwan. Statistical analyses included descriptive statistics, univariate analysis and stepwise regression analysis. RESULTS: Tuberculosis tended to be associated with less education, male sex, malnutrition, cigarette smoking and unhealthy lifestyle habits before the tuberculosis diagnosis. The percentage of smoking decreased from 46.9% before to 30.2% after the tuberculosis diagnosis. Body mass index and health-promoting behaviours also significantly improved after tuberculosis treatment. After controlling for potential confounding factors, multivariate analysis identified chronic disease and completed treatment as significant factors that were associated with current health-promoting behaviours. CONCLUSIONS: A high prevalence of cigarette smoking and low levels of health-promoting behaviours were observed before the diagnosis and during or after completing tuberculosis treatment. RELEVANCE TO CLINICAL PRACTICE: This study's findings indicate the importance of promoting healthy lifestyle changes among tuberculosis patients; aggressive measures should be implemented immediately after the first diagnosis of tuberculosis. Furthermore, health promotion and smoking cessation programmes should be initiated in the general population to prevent activation of latent tuberculosis infection, and these programmes should specifically target men and rural residents. PMID- 27265067 TI - Advances in obstetric dermatology: A better understanding of skin disease in pregnancy. PMID- 27265068 TI - Dermatoses of pregnancy: Nomenclature, misnomers, and myths. AB - The most recent reclassification of dermatoses of pregnancy includes polymorphic eruption of pregnancy, atopic eruption of pregnancy, and pemphigoid gestationis; intrahepatic cholestasis of pregnancy, strictly not a dermatosis, was included in specific dermatoses of pregnancy for working purposes. Another dermatosis, pustular psoriasis of pregnancy, could be included for similar reasons. The nomenclature of these pregnancy-specific eruptions has been revised several times, generating potential confusion among practitioners. Clouding the picture further are misnomers that have been used to describe dermatoses of pregnancy. In addition, several cutaneous conditions that are associated with, but not specific to, pregnancy, have been misunderstood, which has resulted in certain myths among patients and physicians. In this contribution, we describe how the nomenclature of each dermatosis of pregnancy has evolved to fit the current classification scheme. We then identify several misnomers that have generated confusion within the scheme. Finally, we debunk several myths that have developed around cutaneous conditions outside of this scheme, in both mother and newborn. PMID- 27265070 TI - Intrahepatic cholestasis of pregnancy: Recent advances. AB - Intrahepatic cholestasis of pregnancy, also known as obstetric cholestasis, is a pruritic condition of pregnancy characterized by an underlying elevation in circulating bile acids and liver derangement, and associated with adverse fetal outcomes, such as preterm labor and stillbirth. Limited understanding of the underlying pathophysiology and mechanisms involved in adverse outcomes has previously restricted treatment options and pregnancy management. Recent advances in these research fields provide tantalizing targets to improve the care of pregnant women affected by this condition. PMID- 27265069 TI - Skin disease in pregnancy: The approach of the obstetric medicine physician. AB - This review presents the approach of the obstetric medicine physician to skin disease in pregnancy. It elaborates on common skin-related problems during gestation, such as pruritus, with or without eruption, and drug eruptions. An algorithmic approach to the differential diagnosis of pruritus in pregnancy is outlined. Also, the review focuses on how to diagnose promptly endocrinopathies presenting with skin manifestations in pregnancy, such as Addison disease, diabetes, and hyperthyroidism. The prompt diagnosis of endocrine disorders can help to optimize management and improve outcomes. Finally, the authors outline their approach to minimizing maternal and fetal risks associated with skin disease. The risks associated with obstetric cholestasis, pemphigoid gestationis, and impetigo herpetiformis are discussed. Prompt diagnosis helps to minimize the serious risks associated with certain infections. Preconception counseling and a multidisciplinary approach are crucial to preventing risks associated with rheumatic skin disease and genodermatoses. Challenging, real-life obstetric medicine cases are discussed. PMID- 27265071 TI - Inflammatory and glandular skin disease in pregnancy. AB - A switch from cell-mediated to humoral immunity (helper T 1 [Th1] to helper T 2 [Th2] shift) during gestation plays a key role in placental immune tolerance. As a result, skin diseases that are Th2 mediated often worsen, whereas skin diseases that are Th1 mediated often improve during gestation. Also, due to fluctuations in glandular activity, skin diseases involving sebaceous and eccrine glands may flare, whereas those involving apocrine glands may improve during pregnancy. Despite these trends, inflammatory and glandular skin diseases do not always follow the predicted pattern, and courses are often diverse. We review the gestational course of inflammatory skin diseases, such as atopic dermatitis (atopic eruption of pregnancy), psoriasis, impetigo herpetiformis, urticaria, erythema annulare centrifugum, pityriasis rosea, sarcoidosis, Sweet syndrome, and erythema nodosum, as well as glandular skin diseases, including acne vulgaris, acne rosacea, perioral dermatitis, hidradenitis suppurativa, Fox-Fordyce disease, hyperhidrosis, and miliaria. For each of these diseases, we discuss the pathogenesis, clinical presentation, and management with special consideration for maternal and fetal safety. PMID- 27265072 TI - Management of rheumatic and autoimmune blistering disease in pregnancy and postpartum. AB - The treatment of rheumatic and autoimmune skin disease in women who are pregnant or of childbearing potential can present challenges to the dermatologist. We discuss the current approaches to treating lupus erythematosus, antiphospholipid antibody syndrome, dermatomyositis, morphea and systemic sclerosis, mixed connective tissue disease, rheumatoid arthritis, and autoimmune blistering disease in such patients. In the appropriate setting, topical and systemic corticosteroids, hydroxychloroquine, dapsone, azathioprine, and ultraviolet B phototherapy may be safely and cautiously used during pregnancy. Considerations about contraception, planned conception, therapeutic options, and disease control are paramount in optimizing pregnancy outcomes and minimizing risks to both mother and fetus. PMID- 27265073 TI - Oral and vulvovaginal changes in pregnancy. AB - Physiologic alterations of the oral and vulvovaginal mucosal surfaces result from the profound hormonal and immunologic changes of gestation. High estrogen levels are responsible for the vascular changes noted on mucosal surfaces. Gingival hyperemia and edema, gingivitis and pyogenic granuloma are the most common alterations of the oral mucosa during gestation. Physiologic changes of the vulvovaginal area are mainly of vascular nature, and include among others varicose veins. The oral and vulvovaginal mucosal surfaces can be affected by diseases that can worsen or develop in pregnancy. Oral lesions are encountered in a large spectrum of diseases including aphthosis, pemphigus vulgaris, systemic lupus, and Behcet disease. Pregnancy dermatoses such as impetigo herpetiformis and gestational pemphigoid can exceptionally affect the oral mucosa. Infections of the vulvovaginal region by Candida species, Trichomononas vaginalis, human papilloma virus, and herpes simplex virus have been associated with fetal risks. The dermatologist, obstetric medicine physician, and neonatologist should be familiar with the above physiologic changes as well as maternal/fetal risks relevant to disease affecting these mucosal surfaces during gestation. PMID- 27265074 TI - Cutaneous tumors in pregnancy. AB - Pregnancy alters the frequency and natural course of certain skin tumors. Pregnancy-associated changes in melanocytic nevi are transient, and there is no substantiated evidence of increased risk of malignant transformation of melanocytic nevi in gestation. Characteristic vascular and pigment-related dermatoscopic features are helpful in evaluating pigmented lesions, but a biopsy should be performed for significant change or other worrisome features in a lesion. Outcomes for pregnancy-associated melanoma do not appear to be poorer compared with nonpregnancy melanoma; however, data are limited for advanced (stage III/IV) melanoma. Some studies suggest increased propensity for lymphovascular spread, but more data are needed for definitive conclusions and guidelines on prognostication, workup, and treatment of pregnancy-associated melanoma. Vascular tumors, particularly pyogenic granuloma (granuloma gravidarum), occur with increased frequency and are associated with pro angiogenic hormonal influences. Dermatofibrosarcoma protuberans has a more aggressive course during pregnancy with both prompt surgical treatment and close monitoring for recurrence being indicated. PMID- 27265075 TI - Skin infections in pregnancy. AB - A wide array of infectious diseases can occur in pregnancy. Their acquisition, clinical presentation, and course during gestation may be altered due to an impairment of the maternal cellular immunity. Some infectious diseases can lead to serious consequences for the mother or the offspring, including congenital malformations. This review describes in detail the clinical presentation, course, management, and associated maternal and fetal risks of selected viral (varicella zoster virus infections, condylomata acuminata), fungal (candida vulvovaginitis), bacterial (Lyme borreliosis), and parasitic (scabies) infections. The treatment options are critically reviewed. First-line therapies include acyclovir and varicella-zoster virus immunoglobulin for varicella-zoster virus infections, surgical modalities for genital warts, topical clotrimazole and oral fluconazole for Candida vulvovaginitis, amoxicillin and cefuroxime for Lyme borreliosis, and permethrin for scabies. A synopsis of maternal and fetal risks of other important infections is also included. PMID- 27265076 TI - Pemphigoid gestationis: Toward a better understanding of the etiopathogenesis. AB - Pemphigoid gestationis (PG) is the only autoimmune disease exclusively emerging in pregnancy. It belongs to the pemphigoid group of disorders, a class of autoimmune blistering skin diseases featuring an immune response against different hemidesmosomal proteins. PG is caused by a break of immunotolerance against the hemidesmosomal protein BP180. Several lines of evidence suggest that this break of immunotolerance is linked to specific maternal major histocompatibility complex (MHC) class II gene variants and aberrant expression of MHC class II molecules in the placenta. The close time association of the emergence of PG with pregnancy and the obviously very short period required from the initial break of immunotolerance to the onset of skin inflammation set PG into a unique position among autoimmune diseases in view of the fact that, for other autoimmune diseases, the time and site of the break of immunotolerance are usually vastly elusive and the period of silent disease can only be speculated on. In this review we highlight the features of PG and summarize current knowledge about its pathogenesis. We believe that this disease offers the best opportunity to elucidate comprehensively all phases of the pathogenesis of an autoantibody-driven disease. PMID- 27265077 TI - Polymorphic eruption of pregnancy. AB - Polymorphic eruption of pregnancy (PEP), a specific dermatosis of pregnancy also known as pruritic urticarial papules and plaques of pregnancy (PUPPP), is a benign, self-limited skin disorder. Key features include an increased prevalence in primigravidas, onset in the third trimester, remission near the time of delivery, and association with multiple gestation pregnancy. The clinical features are crucial to diagnosis. Histopathology is nonspecific, and immunofluorescence studies help differentiate PEP from pemphigoid gestationis. The pathogenesis of PEP remains elusive, and relevant theories are reviewed. There are no associated maternal or fetal risks, and treatment is largely symptomatic. PMID- 27265078 TI - Prurigo, pruritic folliculitis, and atopic eruption of pregnancy: Facts and controversies. AB - Prurigo (PP) and pruritic folliculitis of pregnancy (PFP) are poorly characterized entities. Traditionally classified under specific dermatoses of pregnancy, they were reclassified under a new umbrella entity, atopic eruption of pregnancy (AEP), which also includes atopic dermatitis (AD) that can worsen or present for the first time in pregnancy. Still, several aspects of AEP have not been adequately elucidated. It needs to be clarified whether it is the intrinsic ("nonallergic" or "atopiform dermatitis") or extrinsic (immunoglobulin E associated) AD that is affected by pregnancy. Future studies need to examine the postpartum prognosis of AD that develops for the first time during gestation. A revision of diagnostic criteria of AEP will allow a more accurate estimate of its prevalence, as well as clarification of the relationship between AD and specific dermatoses, such as PP and PFP. In this context, this review discusses the history, epidemiologic data, clinicopathologic features, and management of these entities. PMID- 27265079 TI - Drug safety: Pregnancy rating classifications and controversies. AB - This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation. PMID- 27265080 TI - Performing research in pregnancy: Challenges and perspectives. AB - There are numerous barriers to conducting clinical research in pregnancy, including ethical considerations, logistical difficulties, and federal regulations. Due to these challenges, there is a paucity of data on the safe and appropriate use of dermatologic therapies in pregnancy, even for easily accessed over-the-counter topical products, as well as for commonly prescribed medications. Given the lack of human safety data, the Food and Drug Administration pregnancy labeling system previously placed a high priority on animal data but was recently revised to highlight human data and pregnancy registries. The latter can provide prospective observational data on medication use in pregnant women, while avoiding many of the pitfalls of conducting clinical trials in this population; nevertheless, registry enrollment for dermatologic drugs remains low. Dermatologists must increase awareness of pregnancy registries and encourage patient enrollment to close this knowledge gap. PMID- 27265081 TI - 10th World Congress of the International Academy of Cosmetic Dermatology, Rio de Janeiro, Brazil, November 14-16, 2015. PMID- 27265082 TI - My personal experiences at the BEST Medical Center: A day in the clinic-the morning. AB - Dr. Ida Lystic is a gastroenterologist who trained at the OTHER (Owen T. Henry and Eugene Rutherford) Medical Center, after having completed her MD degree at the prestigious Harvey Medical School (recently renamed the Harvey Provider School). She accepted a faculty position at the BEST (Byron Edwards and Samuel Thompson) Medical Center. Dr. Lystic shares her experiences on a typical morning in gastroenterology clinic. Although her clinic start date was delayed by 2 months after becoming sick following a mandatory flu shot and having to complete more than 70 hours of compliance training modules, she is now familiar with the BEST system. Clinic scheduling priorities include ensuring that the staff can eat lunch together and depart at 5:00 pm. It is a continual challenge to find time to complete the electronic medical record after BEST changed from the SIMPLE (Succinct Input Making Patients Lives Electronic) system to LEGEND (referred to as Lengthy and Excessively Graded Evaluation and Nomenclature for Diagnosis by her colleagues). To maintain clinic punctuality, a compliance spreadsheet is e mailed monthly to the Wait Time Committee. Their most recent corrective action plan for tardy physicians included placing egg timers on the doors and having nurses interrupt visits that exceed the allotted time. Administrative decisions have resulted in downsizing personnel. Patients are required to schedule their own tests and procedures and follow-up appointments-causing low patient satisfaction scores; however, the money saved lead to a large year-end bonus for the vice president of BEST Efficiency, who holds "providers" accountable for the poor patient experience. Although Dr. Ida Lystic and the gastroenterology clinic at "the BEST Medical Center" are creations of the authors' imagination, the majority of the anecdotes are based on actual events. PMID- 27265083 TI - The "dangers of cybernetic medicine-a dermatologist's warning". AB - Confining the actions of physicians to iron-clad directions and blind following of rules and regulations is creating many problems. Not to err does not mean to be right. Overall supervision of medical research and practice is a must for society; yet, minute regulations become a major obstacle for good practice and progress. Medicine is about patients and physicians. Pre-established rules and directives are only tools, not ends in themselves. Societies or institutions that become rigid and inefficient tend to be wiped out when unexpected situations or enemies appear. As a result, the stereotyped measures are not sufficiently effective. The deterioration of the Roman empire, and of its formidable army, is used as an historical example of the viewpoint proposed by the author. The analysis presented here applies to dermatology in particular, but also, and very acutely, to medicine in general. PMID- 27265084 TI - Erratum to "Leprosy in the bible" [Clin Dermatol 2016:34 3-7]. PMID- 27265085 TI - Erratum to "Severity score indexes for blistering diseases" [Clin Dermatol 2011:30 108-113]. PMID- 27265086 TI - Erratum to "The fate of Hungarian Jewish dermatologists during the Holocaust. Part 1: Six refugees who fled": [Clin Dermatol 2016: 34 293-298]. PMID- 27265087 TI - Optimized hydraulic retention time for phosphorus and COD removal from synthetic domestic sewage with granules in a continuous-flow reactor. AB - In continuous-flow reactor (CFR), suboptimal hydraulic retention time (HRT) can affect the substrate loading, anaerobic time and aerobic time and further affect the performance and characteristics of granules, thus different HRTs (7.5, 6.0, 4.5 and 5.2h) were tested to improve the phosphorus (P) and carbon (COD) removal of the continuous-flow system with granules in this study. When HRT was below 6.0h, the COD removal efficiency in anaerobic zone and the P removal efficiency in aerobic zone reduced obviously, and the settling ability of EBPR granules deteriorated. The residual COD in anaerobic zone resulted in the proliferation of filamentous bacteria on the granules surface. Pyrosequencing analysis revealed that Proteobacteria was the dominant phylum in this system. The dominant class transformed from Betaproteobacteria to Gammaproteobacteria when HRT was reduced from 6.0h to 4.5h. PMID- 27265089 TI - Editor's perspectives - June 2016. PMID- 27265088 TI - Cellulose: A review as natural, modified and activated carbon adsorbent. AB - Cellulose is a biodegradable, renewable, non-meltable polymer which is insoluble in most solvents due to hydrogen bonding and crystallinity. Natural cellulose shows lower adsorption capacity as compared to modified cellulose and its capacity can be enhanced by modification usually by chemicals. This review focuses on the utilization of cellulose as an adsorbent in natural/modified form or as a precursor for activated carbon (AC) for adsorbing substances from water. The literature revealed that cellulose can be a promising precursor for production of activated carbon with appreciable surface area (~1300m(2)g(-1)) and total pore volume (~0.6cm(3)g(-1)) and the surface area and pore volume varies with the cellulose content. Finally, the purpose of review is to report a few controversies and unresolved questions concerning the preparation/properties of ACs from cellulose and to make aware to readers that there is still considerable scope for future development, characterization and utilization of ACs from cellulose. PMID- 27265090 TI - Autonomic nervous system function predicts the inflammatory response over three years in newly diagnosed ulcerative colitis patients. AB - BACKGROUND: The autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC). METHODS: We prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years. KEY RESULTS: Sympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-alpha, IFN gamma) and mucosal inflammation (interleukin-8, IFN-gamma) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-alpha. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up. CONCLUSIONS & INFERENCES: This study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC. PMID- 27265092 TI - Atypical flat warts in an immunocompromised patient. PMID- 27265091 TI - The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants. AB - The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a "false positive report", we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers. PMID- 27265093 TI - Reply: Psychiatric Symptoms in Patients with Stroke: A Six-Month Follow-Up Study. PMID- 27265094 TI - Motor Skills Training Improves Sensorimotor Dysfunction and Increases Microtubule Associated Protein 2 mRNA Expression in Rats with Intracerebral Hemorrhage. AB - BACKGROUND: In this study, we examined the effects of motor skills training on the sensorimotor function and the expression of genes associated with synaptic plasticity after intracerebral hemorrhage (ICH) in rats. METHODS: Male Wistar rats were subjected to ICH or sham operation. ICH was caused by the injection of collagenase into the left striatum. Rats were randomly assigned to no training, acrobatic training, and sham groups. The acrobatic group performed 5 types of acrobatic tasks from 4 to 28 days after surgery. The forelimb sensorimotor function was evaluated over time using forepaw grasping, forelimb placing, and postural instability tests. At 14 and 29 days after the lesion, we analyzed the mRNA expression levels of microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor, and growth-associated protein 43 in the bilateral sensorimotor cortex (forelimb area) by real-time reverse transcription-polymerase chain reaction. RESULTS: Motor skills training in ICH rats improved the sensorimotor dysfunction significantly from the early phase. The mRNA expression level of MAP2 was upregulated in the ipsilesional sensorimotor cortex by motor skills training at 29 days after the lesion. CONCLUSIONS: Our results suggest that sensorimotor functional recovery following motor skills training after ICH is promoted by dendritic growth in the ipsilesional sensorimotor cortex. PMID- 27265095 TI - The Influence of Rocker Bar Ankle Foot Orthosis on Gait in Patients with Chronic Hemiplegia. AB - BACKGROUND: This study aimed to evaluate the effect of rocker bar ankle foot orthosis (RAFO) on the spatiotemporal characteristics of gait in chronic hemiplegic patients compared with the effect of solid ankle foot orthosis (SAFO). METHODS: Following ethical approval, 18 patients with chronic hemiplegia, at least 6 months post stroke, were investigated in barefoot condition, with SAFO and RAFO in random sequences. Their spatiotemporal characteristics were examined by 2 force platforms and a Vicon motion analysis system. RESULTS: There were significant changes in spatiotemporal outcome measures between barefoot condition and using SAFO and RAFO (P < .05). Compared with SAFO, RAFO resulted in significantly more step length, faster gait velocity, and less preswing time (P < .05), although no significant differences were seen regarding step width and cadence (P > .05). Furthermore, RAFO led to significant increases in hip extension and knee flexion at toe-off, whereas SAFO did not change these parameters (P < .05). CONCLUSION: Findings of the present study showed that RAFO further improves gait abilities in chronic hemiplegic patients compared with SAFO, which could be due to the positive effect of added rocker bar on push-off function during the late stance phase of gait. PMID- 27265096 TI - Erratum to "Charcot-Marie-Tooth type 2 and distal hereditary motor neuropathy: Clinical, neurophysiological and genetic findings from a single-centre experience" [Clin. Neurol. Neurosurg. 144 (2016) 67-71]. PMID- 27265098 TI - Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores. AB - The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 A to 40 A were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials. PMID- 27265100 TI - New insights into the genetics of congenital neutropenia. AB - Several congenital disorders may cause neutropenia. The recent advances in the field of molecular biology have facilitated our knowledge concerning pathophysiological mechanisms leading to these disorders. The molecular basis of disorders with defective myelopoiesis (severe congenital neutropenia and cyclic neutropenia) and disorders due to defective RNA processing (Shwachman Diamond syndrome and cartilage hair hypoplasia) are the two congenital neutropenia syndromes that are addressed in this review. Molecular defects defined by means of these disorders are very important for our understanding of the cause of the disorders as well as some unknown molecular mechanisms. PMID- 27265099 TI - Marinobacterium zhoushanense sp. nov., isolated from surface seawater. AB - A Gram-stain-negative, facultatively anaerobic bacterium, designated WM3T, was isolated from surface seawater collected from the East China Sea. Cells were catalase- and oxidase-positive, short rods and motile by means of a single polar flagellum. Growth occurred at 15-43 degrees C (optimum 37-40 C), pH 5.5-9.5 (optimum pH 6.5-7.5) and with 0.25-9.0 % (w/v) NaCl (optimum 1.0-1.5 %). Chemotaxonomic analysis showed that the respiratory quinone was ubiquinone-8, the major fatty acids included C16 : 0 (23.6 %), C18 : 1omega7c (26.2 %) and summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2-OH, 22.1 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain WM3T was most closely related to the genus Marinobacterium, sharing the highest 16S rRNA gene sequence similarity of 95.5 % with both Marinobacterium litorale KCTC 12756T and Marinobacterium mangrovicola DSM 27697T. The genomic DNA G+C content of the strain WM3T was 55.8 mol%. On the basis of phenotypic, chemotaxonomic and genotypic characteristics presented in this study, strain WM3T is suggested to represent a novel species of the genus Marinobacterium, for which the name Marinobacterium zhoushanense sp. nov. is proposed. The type strain is WM3T (=KCTC 42782T=CGMCC 1.15341T). PMID- 27265097 TI - Efficacy of a Universal Brief Intervention for Violence Among Urban Emergency Department Youth. AB - BACKGROUND: Violent injury is the leading cause of death among urban youth. Emergency department (ED) visits represent an opportunity to deliver a brief intervention (BI) to reduce violence among youth seeking medical care in high risk communities. OBJECTIVE: The objective was to determine the efficacy of a universally applied BI addressing violence behaviors among youth presenting to an urban ED. METHODS: ED youth (14 to 20 years old) seeking medical or injury related care in a Level I ED (October 2011-March 2015) and screening positive for a home address within the intervention or comparison neighborhood of a larger youth violence project were enrolled in this quasi-experimental study. Based on home address, participants were assigned to receive either the 30-minute therapist-delivered BI (Project Sync) or a resource brochure (enhanced usual care [EUC] condition). The Project Sync BI combined motivational interviewing and cognitive skills training, including a review of participant goals, tailored feedback, decisional balance exercises, role-playing exercises, and linkage to community resources. Participants completed validated survey measures at baseline and a 2-month follow-up assessment. Main outcome measures included self-report of physical victimization, aggression, and self-efficacy to avoid fighting. Poisson and zero-inflated Poisson regression analyses analyzed the effects of the BI, compared to the EUC condition, on primary outcomes. RESULTS: A total of 409 eligible youth (82% participation) were enrolled and assigned to receive either the BI (n = 263) or the EUC condition (n = 146). Two-month follow-up was 91% (n = 373). There were no significant baseline differences between study conditions. Among the entire sample, mean (+/-SD) age was 17.7 (+/-1.9) years, 60% were female, 93% were African American, and 79% reported receipt of public assistance. Of participants, 9% presented for a violent injury, 9% reported recent firearm carriage, 20% reported recent alcohol use, and 39% reported recent marijuana use. Compared with the EUC group, participants in the therapist BI group showed self reported reductions in frequency of violent aggression (therapist, -46.8%; EUC, 36.9%; incident rate ratio [IRR] = 0.87; 95% confidence interval [CI] = 0.76 to 0.99) and increased self-efficacy for avoiding fighting (therapist, +7.2%; EUC, 1.3%; IRR = 1.09; 95% CI = 1.02 to 1.15). No significant changes were noted for victimization. CONCLUSIONS: Among youth seeking ED care in a high-risk community, a brief, universally applied BI shows promise in increased self-efficacy for avoiding fighting and a decrease in the frequency of violent aggression. PMID- 27265101 TI - Factor V 1691 G-A mutation distribution in a healthy Turkish population. AB - The aim of this review was to compile published data on factor V 1691 G-A alteration in a healthy Turkish population and also to stimulate the reporting of unpublished data, in order to create a map for factor V Leiden (FVL) in Turkey. From a total of 4276 healthy individuals from 26 different centers of Turkey, 345 FVL carriers (7.9%) were determined. FVL was strikingly high among newborns from two different centers (10.9%). PMID- 27265102 TI - Transient depletion of innate immunity in varicella infections in otherwise healthy children. AB - OBJECTIVE: Varicella is a common childhood infection and has a number of complications in the unvaccinated population. Perforin, found in natural killer cells, is important for the killing of virally infected cells. For this reason, the aim of this study was to determine natural killer cell count and activity, perforin expression, and Fas and soluble Fas ligand (sFas-L) levels in immunocompetent children with varicella infection and define any possible relations between the levels and varicella complications. METHODS: Forty children were analyzed at diagnosis and on the 15th day of varicella infection. There was a significant difference in hemoglobin levels and leukocyte and platelet counts between days 0 and 15. RESULTS: Thirteen (32%) patients were found to be lymphopenic. Natural killer cell count and activity were significantly higher on day 15 when compared to values at diagnosis. The Fas-mediated apoptotic pathway was found to be active in acute varicella infection because Fas and sFas-L levels at diagnosis were higher than values on day 15. CONCLUSION: These findings suggest that the Fas and Fas-L apoptotic pathway is active during the acute phase of the viral infection and that it becomes inactive by day 15, paralleling the hematologic recovery. PMID- 27265103 TI - Hb D-Los Angeles [beta121(GH4)Glu>Gln] and Hb Beograd [beta121(GH4)Glu>Val]: Implications for their laboratory diagnosis and genetic origins. AB - OBJECTIVE: The aim of this study was to determine the laboratory diagnosis and genetic origins of the hemoglobin (Hb) variants, Hb D-Los Angeles and Hb Beograd observed frequently in our region. MATERIAL AND METHODS: Hb variants were investigated in one Hb D-Los Angeles and two Hb Beograd families. These families were unrelated with each other. For the determination of Hb variants, alkaline/acid electrophoresis, HPLC, DE-52 micro-column chromatography procedures were applied. Mutations were determined by non-radioactive fluorescence automated DNA sequencing. Beta globin gene cluster haplotypes were identified by RFLP analysis at seven loci known as epsilon-Hinc II, Ggamma-Hind III, APsibeta-Hind III, 5'Psibeta-Hinc II, 3'Psibeta-Hinc II, beta-Ava II ve 3'beta-Hinf I. RESULTS: Three novel beta globin gene cluster haplotypes were identified as in relation with Hb D-Los Angeles [--+-+++], Hb Beograd [+----++ and -+-(+/-)(+/-)+(+/-)]. These haplotypes were reported for the first time in the world population Conclusion: In this study we emphasize the importance of DNA seqeuncing and other laboratory procedures for the identification of Hb variants in premarital diagnosis. On the other hand we discuss also the genetic origins of these Hb variants. PMID- 27265104 TI - The estimation of platelet count from a blood smear on the basis of the red cell: platelet ratio. AB - OBJECTIVE: The estimation of platelet count from blood smears is a daily routine laboratory test, which should be systematic each time the automated count is erroneous. In our laboratory, we estimate the platelet count indirectly by using the automated red blood cell (RBC) and calculating the platelet count on the basis of the red cell: platelet ratio in a stained blood film. In this study, we attempted to verify the reliability of this technique. MATERIAL AND METHODS: One hundred ninety-one platelet counts were executed by two laboratory methods: an automated count using an impedance cell counter and then a manual method by reviewing microscopic blood smears. The number of platelets per 1000 erythrocytes was multiplied by the automated RBC (x106 cells/ul) to give an approximate manual count (x103 cells/ul). Two paired t-test was used for comparison of the two methods. RESULTS: The regression analyses for the entire data set collected in our study with the two laboratory methods gave the following least squares equation by comparing the automated (y) to the manual method (x): y=0.8548x + 12.013 (r=0.908). The paired t-test showed no significant difference between the two methods (p>0.05) and the Intra-class Correlation Coefficient (ICC) was equal to 0.905. The plot of the differences between the automated and manual values against their means according to Band and Altman design showed that the difference mean was 3.209 with a standard deviation SD=46.331. We noticed that 93% of the differences were within the agreement limits (mean+/-2SD), and that 77% of the differences were less than 20,000 platelets/ul. CONCLUSION: Estimating platelet count on the basis of the red cell: platelet ratio is a reliable technique and it should be proposed as a method of reference. PMID- 27265105 TI - Clinical and hematological manifestations of visceral leishmaniasis in Yemeni children. AB - OBJECTIVE: In southeast Yemen, visceral leishmaniasis (VL) is endemic in Lahj and Abyan and also in Hagga and Sadah, the areas lacking adequate diagnostic facilities. This study describes the clinical and hematological features in 64 cases of childhood VL. METHODS: All children below 12 years of age who were managed as inpatient cases from 1 January to 31 December 2005 were included in this study. The diagnosis of VL was established by demonstration of leishmania parasites in bone marrow aspiration. Demographic information, physical signs at presentation and results of complete blood count were recorded and bone marrow aspirations were done for LD bodies. RESULTS: Mean age of the patients was 30 months, and there were 33 females and 31 males. Fever was seen in 100% of children with duration before diagnosis of 56 days. Splenomegaly was present in all cases and hepatomegaly in 84.4%, with mean enlargement of spleen and liver of 9.3 and 3.5 cm, respectively. Mean hemoglobin level, white blood cell and platelet counts were 6.6 g/dl, 3.58x109 /L and 71.7x109 /L, respectively. Absolute neutrophil count was <0.78x109 /L and mean reticulocyte count was 1.7%. CONCLUSION: Fever, hepatosplenomegaly and pancytopenia were the most common clinical and hematological manifestations in Yemeni children with VL. PMID- 27265106 TI - Identification of gold nanoparticle in lymphocytes: a confirmation of direct intracellular penetration effect. AB - OBJECTIVE: Nanoparticles differ from the same material at larger scale in chemical and physical properties. The effect of nanoparticle on the blood cell still needs scientific verification. METHODS: The direct effect of gold nanoparticles on lymphocyte was direct assessed by in vitro assay. RESULTS: In this work, the author reported additional results from specific observation on lymphocyte exposure to gold nanoparticle. CONCLUSION: This result confirms for direct intracellular penetration effect. PMID- 27265107 TI - Aortic aneurysm and non-Hodgkin's lymphoma in Marfan syndrome. AB - The combination of Marfan syndrome with lymphoma is extremely rare. This report describes a case of Marfan syndrome who presented with chest discomfort and was diagnosed to have an aortic aneurysm and an additional incidental mediastinal mass that on further investigation turned out to be a diffuse large B cell lymphoma. We have suggested a hypothesis which can explain the occurrence of lymphoma in Marfan syndrome. PMID- 27265108 TI - Bilateral knee and right ankle osteonecrosis in an adolescent girl with acute lymphoblastic leukemia. AB - Although rare, avascular necrosis of bone is a serious and incapacitating complication seen in children with acute lymphoblastic leukemia receiving high dose steroids. Here we present a 16 year-old girl who developed bilateral knee and right ankle avascular osteonecrosis one year after intensive chemotherapy for medium risk acute lymphoblastic leukemia. Indirect curettage of necrotic tissue and bone grafting were performed for both knees whereas conservative measures had been sufficient for the ankle. Early recognition of this condition is important in prevention of disabling sequela in skeletal system. PMID- 27265109 TI - Acute erythroid leukemia (AML-M6) - Is it rare? PMID- 27265110 TI - Extramedullary hematopoiesis in the axillary lymph node in a patient with an accelerated phase of chronic myeloid leukemia. PMID- 27265111 TI - Familial thrombocytopenia associated with ovarian agenesis, umbilical hernia, bicuspid aortic valve, patent ductus arteriosus and epilepsia. PMID- 27265112 TI - Insulin-like growth factor-1 and zinc in children with Beta thalassemia minor. PMID- 27265113 TI - Brilliant cresyl blue staining for screening hemoglobin H disease: Reticulocyte smear. PMID- 27265114 TI - Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia. AB - The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics((r))) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy. PMID- 27265116 TI - Protective Effects of Quercetin on Selected Oxidative Biomarkers in Bovine Spermatozoa Subjected to Ferrous Ascorbate. AB - Quercetin (QUE) is a natural flavonol-type flavonoid with antibacterial, anti inflammatory and anti-aggregatory properties. It is also a powerful reactive oxygen species (ROS) scavenger and chelating agent. The aim of this study was to assess the effectiveness of QUE to reverse ROS-mediated alterations to the motility, viability and intracellular antioxidant profile of bovine spermatozoa. Spermatozoa were washed out of fresh bovine semen, suspended in 2.9% sodium citrate and subjected to QUE treatment (7.5, 25, 50 and 100 MUmol/l) in the presence or absence of a pro-oxidant, that is ferrous ascorbate (FeAA; 150 MUmol/l FeSO4 and 750 MUmol/l ascorbic acid) during a 6-h in vitro culture. Spermatozoa motion characteristics were assessed using the SpermVision computer aided sperm analysis (CASA) system. Cell viability was examined with the metabolic activity (MTT) assay, ROS generation was quantified via luminometry, and the nitroblue tetrazolium (NBT) test was applied to quantify the intracellular superoxide formation. Cell lysates were prepared at the end of the in vitro culture to investigate the intracellular activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) as well as the concentrations of glutathione (GSH) and malondialdehyde (MDA). FeAA treatment led to a reduced sperm motility (p < 0.001), viability (p < 0.001) and decreased the antioxidant parameters of the sperm samples (p < 0.001) but increased the ROS generation (p < 0.001), superoxide production (p < 0.001) and lipid peroxidation (p < 0.001). QUE administration resulted in a preservation of the spermatozoa vitality and antioxidant characteristics (p < 0.01 with respect to the enzymatic antioxidants, p < 0.001 in relation to GSH) with a concentration range of 50-100 MUmol/l QUE revealing to be the most effective. Our results suggest that QUE exhibits significant ROS-scavenging and metal-chelating properties which may prevent spermatozoa alterations caused by ROS, and preserve the functionality of male reproductive cells. PMID- 27265115 TI - Neurological and digestive bleeding with Direct Oral Anticoagulants versus Vitamin K Antagonists: The differences do not stop there! A pharmacovigilance study. PMID- 27265117 TI - Structural and functional studies of a large winged Z-DNA-binding domain of Danio rerio protein kinase PKZ. AB - The Z-DNA-binding domain of PKZ from zebrafish (Danio rerio; drZalphaPKZ ) contains the largest beta-wing among known Z-DNA-binding domains. To elucidate the functional implication of the beta-wing, we solved the crystal structure of apo-drZalphaPKZ . Structural comparison with its Z-DNA-bound form revealed a large conformational change within the beta-wing during Z-DNA binding. Biochemical studies of protein mutants revealed that two basic residues in the beta-wing are responsible for Z-DNA recognition as well as fast B-Z transition. Therefore, the extra basic residues in the beta-wing of drZalphaPKZ are necessary for the fast B-Z transition activity. PMID- 27265119 TI - Fluctuation in seed abundance has contrasting effects on the fate of seeds from two rapidly germinating tree species in an Asian tropical forest. AB - The seed predator satiation hypothesis states that high seed abundance can satiate seed predators or seed dispersers, thus promoting seed survival. However, for rapidly germinating seeds in tropical forests, high seed abundance may limit dispersal as the seeds usually remain under parent trees for long periods, which may lead to high mortality due to rodent predation or fungal infestations. By tracking 2 species of rapidly germinating seeds (Pittosporopsis kerrii, family Icacinaceae; Camellia kissi, family Theaceae), which depend on dispersal by scatter-hoarding rodents, we investigated the effects of seed abundance at the community level on predation and seed dispersal in the tropical forest of Xishuangbanna Prefecture, Southwest China. We found that high seed abundance at the community level was associated with delayed and reduced seed removal, decreased dispersal distance and increased pre-dispersal seed survival for both plant species. High seed abundance was also associated with reduced seed caching of C. kissi, but it showed little effect on seed caching of P. kerrii. However, post-dispersal seed survival for the 2 plant species followed the reverse pattern. High seed abundance in the community was associated with higher post dispersal survival of P. kerrii seeds, but with lower post-dispersal survival of C. kissi seeds. Our results suggest that different plant species derive benefit from fluctuations in seed production in different ways. PMID- 27265118 TI - The Nature and Impact of Side Reactions in Glyme-based Sodium-Oxygen Batteries. AB - Although Na-O2 batteries have a low overpotential and good capacity retention, degradation reactions of glyme-based electrolytes are the primary reason for inefficiency in cell performance. The discharge capacity is accounted for through analysis of the side-products. Although sodium superoxide is the primary product (90 % theoretical), quantitative and qualitative evaluation of the side-products (using (1) H NMR, iodometric titration, and on-line mass spectrometry) shows the presence of sodium acetate (~3.5 %), and three-fold less sodium formate, methoxy (oxo)acetic anhydride, and sodium carbonate. Our reaction mechanism proposes two paths for their formation. Because the side-products are not fully removed during oxidation, they accumulate on the cathode upon cycling. Resting the cell at open circuit potential during discharge results in consumption of the superoxide through the reaction with diglyme, which greatly increases the fraction of side products, as also confirmed by ex situ reaction studies. These findings have implications in the search for more stable electrolytes. PMID- 27265120 TI - Functional porous carbon-ZnO nanocomposites for high-performance biosensors and energy storage applications. AB - A one-pot synthesis method for the fabrication of biomass-derived activated carbon-zinc oxide (ZAC) nanocomposites using sugarcane bagasse as a carbon precursor and ZnCl2 as an activating agent is reported. For the first time, we used ZnCl2 as not only an activating agent and also for the synthesis of ZnO nanoparticles on the AC surface. ZAC materials with varying ZnO loading were prepared and characterized by a variety of analytical and spectroscopic techniques such as FE-SEM, FE-TEM, XRD, EA, XPS, and Raman spectroscopy. ZAC modified glassy carbon electrodes (GCEs) were found to exhibit remarkable electrochemical properties for simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) as well as hazardous pollutants such as hydrogen peroxide (H2O2) and hydrazine (N2H4) with desirable sensitivity, selectivity, and detection limits. Moreover, ZAC-modified stainless steel electrodes also showed superior performances for supercapacitor applications. The ZAC nanocomposites, which may be mass produced by the reported facile direct route from sugarcane bagasse, are not only eco-friendly but also cost-effective, and thus, are suitable as a practical platform for bio-sensing and energy storage applications. PMID- 27265122 TI - Cytokines 2015 - A most memorable meeting. PMID- 27265121 TI - Thoracic Paravertebral Block versus Epidural Anesthesia Combined with Moderate Sedation for Percutaneous Nephrolithotomy. AB - OBJECTIVE: To investigate the feasibility of thoracic paravertebral block (TPVB) for percutaneous nephrolithotomy (PCNL) in comparison with epidural anesthesia (EA) combined with moderate sedation. SUBJECTS AND METHODS: One hundred American Society of Anesthesiologists (ASA) I-II adult patients scheduled for first-stage unilateral PCNL were randomly assigned to receive either TPVB or EA. All patients were given standard sedation and analgesia with propofol and sufentanil. Patient characteristics, surgical outcomes, anesthetic outcomes, and time to first use of a patient-controlled intravenous analgesic (PCIA) device and postoperative consumption of sufentanil in the first 24 h were recorded. Intergroup differences of the parameters were analyzed using an independent t test, Mann-Whitney test, and chi2 test as appropriate. RESULTS: Patients who received TPVB consumed more propofol during ureteroscopy (56.2 +/- 28.4 vs. 42.9 +/- 27.5 mg, p < 0.05) and more sufentanil during ureteroscopy (9.7 +/- 4.8 vs. 3.9 +/- 2.7 MUg, p < 0.05) and during PCNL (7.0 +/- 4.3 vs. 1.9 +/- 1.8 MUg, p < 0.05) than those who received EA. The volume fluids infused in patients who received TPVB was less than in those who received EA (854 +/- 362 vs. 1,320 +/- 468 ml, p < 0.05). Time to first PCIA use, postoperative 24-hour consumption of sufentanil, and other parameters were comparable between groups. CONCLUSIONS: In this study, TPVB was as effective and safe as EA in providing intraoperative anesthesia and postoperative analgesia for PCNL, although more sedatives and analgesics were used during PCNL in patients who received TPVB. PMID- 27265123 TI - Effect of Hematocrit and Erythrocyte Density on Intraoperative Blood Loss in Hemophilia A Patients During Total Knee Arthroplasty. AB - Intraoperative blood loss during total knee arthroplasty in patients with hemophilia varies over a wide range (from 300 to 3000 ml). The reasons have not been clarified yet. We studied the dependence of intraoperative blood loss during total knee arthroplasty in patients with hemophilia A on hematocrit and mean erythrocyte density. Intraoperational blood loss >=1000 ml was observed in patients with hematocrit <38.5%. In patients with hematocrit >38.5% this parameter depended on the mean erythrocyte density: in patients with increased erythrocyte density, the risk of intraoperational blood loss >=1000 ml was higher. The increase in erythrocyte density can serve as an indicator of pathological processes, including the processes modulating hemostasis. It can also be assumed that erythrocytes with higher density change blood flow, which affects platelet adhesion to the damaged endothelium. Hematocrit below the threshold level and mean density of erythrocytes above the normal level can be regarded as risk factor for increased intraoperational blood loss. PMID- 27265124 TI - Maintenance of High Cytochrome P450 Expression in HepaRG Cell Spheroids in DMSO Free Medium. AB - We studied the effects of DMSO and fibroblasts during HepaRG cell spheroid formation and conditions of their subsequent culturing on the levels of mRNA of the major cytochromes P450. A protocol of spheroid formation from differentiated HepaRG cells and their culturing in serum- and DMSO-free medium is developed. PMID- 27265125 TI - Plasma Levels of hsa-miR-619-5p and hsa-miR-1184 Differ in Prostatic Benign Hyperplasia and Cancer. AB - Peripheral blood plasma profiles of circulating microRNA expression were analyzed in patients with prostatic cancer and benign hyperplasia. In prostatic cancer, significant increase in hsa-miR-619-5p and hsa-miR-1184 microRNA expression and significant decrease in hsalet-7b-5p and hsa-let-7c-5p microRNA expression were observed. The role of the relationship between the microRNA expression and the activities and functions of host genes with introns encoding these microRNA is discussed. PMID- 27265126 TI - MicroRNA hsa-miR-4674 in Hemolysis-Free Blood Plasma Is Associated with Distant Metastases of Prostatic Cancer. AB - We analyzed microRNA profile in hemolysis-free blood plasma of patients with prostatic cancer. The metastatic form of prostatic cancer was found to be associated with increased levels of hsa-miR-22-3p, hsa-miR-663a, and hsa-miR-4674 in comparison with non-metastatic form. Common candidate target genes of these microRNA include JUNB, KMT2A, and XPO6. PMID- 27265127 TI - Modeling of Magnetite Nanoparticles Behavior under Conditions of Microcirculation and Analysis of In Vivo Toxicity. AB - The behavior of magnetite nanoparticles was studied in the cell chip microcapillaries. No aggregation of magnetite nanoparticles under conditions of long-term circulation was noted. Biodistribution and toxicity of magnetite nanoparticles (14 nm) and aminated magnetite after their intragastric administration to mice were studied in vivo. According to mass spectrometry and microscopy data, accumulation of nanoparticles occurred mainly in the liver cells. PMID- 27265128 TI - Effect of 2-Isobutyl-4,6-dimethyl-5-hydroxypyrimidine on the Growth of Lewis Lung Carcinoma and Survival of Mice. AB - Experiments on male C57Bl/6 mice with transplantable Lewis lung epidermoid carcinoma were performed to evaluate the effect of early or delayed administration of compound SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) on tumor growth and animal survival. Intraperitoneal injection of SNK-411 in doses of 25 and 50 mg/kg on days 2-8 of tumor growth was followed by significant inhibition of tumor growth (by 1.8 and 2.2 times, respectively, in comparison with the untreated control). Administration of this compound on days 8-15 of tumor development had little effect on tumor growth. SNK-411 in doses of 25 and 50 mg/kg (both dosing regimens) significantly increased survival rate and lifespan of animals with tumors. The drugs for verification of this model (Fluorofur, 400 mg/kg; and doxorubicin hydrochloride, 4 mg/kg) were injected intraperitoneally on days 2-4 and 8-10 of tumor development. Administration of Fluorofur and doxorubicin hydrochloride at the late stage was accompanied by significant inhibition of tumor growth (by 1.6 and 1.4 times, respectively). The increase in the survival rate of animals receiving the cytostatic according to standard dosing regimens was less significant than in experiments with SNK-411. PMID- 27265129 TI - Inhibition of Mitochondrial Voltage-Dependent Anion Channels Increases Radiosensitivity of K562 Leukemic Cells. AB - We studied the effect of inhibition of mitochondrial voltage-dependent anion channels with DIDS on radiosensitivity and mitochondrial status of K562 leukemic cells. The number of apoptotic and necrotic cells, mitochondrial transmembrane potential, and mitochondrial mass were evaluated after irradiation of cells in doses of 4 and 12 Gy in the presence and absence of the inhibitor. Inhibition of mitochondrial voltage-dependent anion channels increased radiosensitivity of K562 cells by 50-70% and decreased both mitochondrial transmembrane potential and mitochondrial mass. Inhibitors of voltage-dependent anion channels are promising agents capable of improving the effectiveness of cancer radiotherapy. PMID- 27265130 TI - Loss of Cell Differentiation in HPV-Associated Bladder Cancer. AB - Medical histories of 101 urothelial bladder cancer patients were compared with the results of morphological analysis and biomolecular detection of human papilloma viruses (HPV) in the tumor specimens. DNA of HPV16 (the major type of virus responsible for appearance of cervical carcinoma) was detected in 38 specimens, while mRNA of E6 and E7 oncogenes and E7 oncoprotein of HPV16 were observed in 13 specimens. HPV-positive bladder cancer was characterized by higher degree of cell anaplasia than HPV-negative cancer; in the primary bladder tumor, HPV was detected more often than in recurrent bladder cancer. These data attest to involvement of HPV16 in the genesis of bladder cancer. No correlations of HPV status of bladder tumor with patient's sex, age, and invasion into the muscle layer were revealed. PMID- 27265131 TI - Heterodimer HLA-DM Fused with Constant Fragment of the Heavy Chain of the Human Immunoglobulin Accelerates Influenza Hemagglutinin HA306-318 Loading to HLA-DR1. AB - Major histocompatibility complex class II (MHC II) plays an important role not only in the adaptive immune responses to foreign pathogens, but also in the development of some autoimmune diseases. Non-classical MHC, HLA-DM is directly involved in MHC II loading with the peptide. To study this process, we synthesized recombinant proteins HLA-DR1 and HLA-DM. alpha/beta-Chains of DR1 heterodimer contained C-terminal leucine domains of the fos and jun factors, respectively. Each DM chain contained constant fragment of human antibody heavy chain fused via a long linker domain. In addition, DM alpha-chain carried N165D substitution suppressing potential glycosylation at this site. We observed significant acceleration of DR1 peptide loading with influenza HA306-318 hemagglutinin in the presence of DM, which indicates functionality of recombinant DR1-DM protein couple. Our results can be used to study the presentation of other viral and self-antigens and can become the basis for the development of new drug modeling. PMID- 27265132 TI - Multiwalled Carbon Nanotubules Induce Pathological Changes in the Digestive Organs of Mice. AB - We studied the effects of regular long-term exposure to industrial nanomaterial based on multiwalled carbon nanotubules on the digestive system of mice. Nanomaterial in a concentration of 30 mg/kg was administered with drinking water over 30 days. Tissue specimens from the small intestine and liver were studied by light and electron microscopy. Multiwalled carbon nanotubules caused multiple necrotic foci in the small intestine and mixed parenchymatous degeneration in the liver. These findings suggested that multiwalled carbon nanotubules entering the digestive tract damaged intestinal villi, presumably via mechanical damage to enterocytes. It seems that multiwalled carbon nanotubules could cause degeneration indirectly, by triggering inflammatory reactions and ROS generation. PMID- 27265133 TI - Fibonacci Sequence and Supramolecular Structure of DNA. AB - We proposed a new model of supramolecular DNA structure. Similar to the previously developed by us model of primary DNA structure [11-15], 3D structure of DNA molecule is assembled in accordance to a mathematic rule known as Fibonacci sequence. Unlike primary DNA structure, supramolecular 3D structure is assembled from complex moieties including a regular tetrahedron and a regular octahedron consisting of monomers, elements of the primary DNA structure. The moieties of the supramolecular DNA structure forming fragments of regular spatial lattice are bound via linker (joint) sequences of the DNA chain. The lattice perceives and transmits information signals over a considerable distance without acoustic aberrations. Linker sequences expand conformational space between lattice segments allowing their sliding relative to each other under the action of external forces. In this case, sliding is provided by stretching of the stacked linker sequences. PMID- 27265134 TI - Anticoagulant Effects of Heparin Complexes with Prolyl-Glycine Peptide and Glycine and Proline Amino Acids. AB - The study demonstrates the formation of heparin complexes with prolyl-glycine peptide and proline and glycine amino acids. The method was developed for in vitro production of these complexes at 1:1 dipeptide to heparin molar ratio and 2:1 amino acid to heparin molar ratio. These complexes, unlike the constituents, proline and glycine, exhibited significant anticoagulant, antiplatelet, and fibrin-depolymerization activities of varying degree in vitro and in vivo. The heparin-dipeptide complex produced maximum effect. The dipeptide by itself also showed anticoagulant properties, but less pronounced than in the complex with heparin. PMID- 27265135 TI - Complex Approach to Xenobiotics Hepatotoxicity Testing using a Microfluidic System. AB - We analyzed hepatotoxicity of three drugs: acetaminophen, metformin, and isoniazid. Spheroids of differentiated HepaRG cells cultured under microfluidic conditions were used as the model. Acute toxicity of substances was assessed by analyzing cell viability, while lactate concentration in the culture medium was used as the potential marker for evaluation of chronic exposure and non-lethal side effects of xenobiotics. The results were compared with mitochondrial activity and DNA fragmentation data. The efficiency and possibility of applying the integrated approach for assessment of drug hepatotoxicity are discussed. PMID- 27265136 TI - Dipeptide Piracetam Analogue Noopept Improves Viability of Hippocampal HT-22 Neurons in the Glutamate Toxicity Model. AB - Effect of noopept (N-phenylacetyl-prolylglycine ethyl ester) on viability of neurons exposed to neurotoxic action of glutamic acid (5 mM) was studied in vitro in immortalized mouse hippocampal HT-22 neurons. Noopept added to the medium before or after glutamic acid improved neuronal survival in a concentration range of 10-11-10-5 M. Comparison of the effective noopept concentrations determined in previous studies on cultured cortical and cerebellar neurons showed that hippocampal neurons are more sensitive to the protective effect of noopept. PMID- 27265137 TI - Effect of Cytotoxic Compounds on Activity of Antioxidant Enzyme System in MCF-7 and H1299 Cells. AB - We studied the function of the antioxidant system in tumor cell lines MCF-7 and H1299 that differ by the state of tumor suppressor gene p53. Exposure to different classes of cytotoxic compounds induced several types of antioxidant system responses that depend on the type of cell line. The effects of platinum(II) and platinum(IV) complexes on activity of antioxidant enzymes vary, which can be explained by differences in their accumulation and biotransformation in tumor cells. Triazole and oxazolidinone derivatives had little effect on activity of superoxide dismutase and catalase in H1299 cells, but increased superoxide dismutase activity in MCF-7 cells. PMID- 27265138 TI - Cytoprotective Effect of Peptide Sedatin, an Agonist of MU/delta-Opioid Receptors, on Primary Culture of Pulmonary Fibroblasts of Albino Rats under Conditions of Oxidative Stress. AB - We studied the effects of a synthetic analogue of dermorphin peptide sedatin on DNA synthesis, nucleolar apparatus, and parameters of free radical oxidation in the primary culture of pulmonary fibroblasts under conditions of oxidative stress. Oxidative stress significantly enhanced production of superoxide anion radical in the culture, sufficiently inhibited DNA synthesis in fibroblasts, and reduced the size of cell nuclei and parameters of the nucleolar apparatus. Sedatin prevented accumulation of free radical oxidation products and changes in karyometry parameters induced by oxidative stress. The peptide completely eliminated changes in the parameters of fibroblast nucleolar apparatus and abolished the inhibitory effect of oxidative stress on the number of DNA synthesizing cells. Pretreatment with non-selective opioid receptor antagonist naloxone hydrochloride partially abolished the effects of sedatin in the primary culture of pulmonary fibroblasts. PMID- 27265139 TI - Psychopharmacological Effects of Alkaloid Z77 under Conditions of Posthypoxic Encephalopathy and Mechanisms of Their Development. AB - Psychopharmacological effects of atisine-type diterpene alkaloid Z77 were studied under conditions of experimental posthypoxic encephalopathy. The preparation had a pronounced cerebroprotective effect consisting in normalization of orientation and exploratory behavior and conditioned activity in experimental animals. These changes were accompanied by significant increase in the number of neural stem cells in the paraventricular region of the brain and markedly enhanced production of neurotrophic growth factors by neural tissue microenvironment cells. PMID- 27265140 TI - Effect of Proline-Containing Oligopeptides PGP and RGP on Proliferative and Protein-Synthesizing Activity of Cultured Pulmonary Fibroblasts under Conditions of Oxidative Stress. AB - We studied the effect of glyprolines Pro-Gly-Pro (PGP) and Arg-Gly-Pro (RGP) on the primary culture of pulmonary fibroblasts from newborn albino rats under normal conditions and during oxidative stress. Under physiological conditions, the peptides had no effect on parameters of cell division. Hydrogen peroxide induced intensive oxidative stress accompanied by suppression of protein synthesizing function. When hydrogen peroxide was added to the culture containing the test peptides, correction of the oxidative status was observed accompanied by activation of DNA-synthesizing activity and inhibition of lucigenin-dependent chemiluminescence. PMID- 27265141 TI - Angiogenic Potential of Multipotent Stromal Cells from the Umbilical Cord: an In Vitro Study. AB - The mechanisms of proangiogenic activity of multipotent stromal cells from human umbilical cord were analyzed in vitro. The absence of secreted forms of proangiogenic growth factor VEGF-A in the culture medium conditioned by umbilical cord-derived multipotent stromal cells was shown by ELISA. However, the possibility of paracrine stimulation of cell proliferation, mobility, and directed migration of endothelial EA.hy926 cells was demonstrated by using MTT test, Transwell system, and monolayer wound modeling. The capacity of multipotent stromal cells to acquire the phenotype of endothelium-like cells was analyzed using differentiation media of three types. It was found that VEGF-A is an essential but not sufficient inductor of differentiation of umbilical cord derived multipotent stromal cells into CD31+ cells. PMID- 27265142 TI - Role of Progenitor Cells in Liver Regeneration after Subtotal Resection. AB - In the liver of rats subjected to subtotal liver resection (80% organ weight), the expression of sox9 gene and SOX9 protein content increased and cells with hepatocyte morphology expressing SOX9 appeared; the proportion of cells expressing cytokeratin-19 also increased. Based on these data, we cannot completely exclude the involvement of resident progenitor cells and hepatocyte reprogramming in liver regeneration after subtotal resection, however, the contribution of these processes seems to be insignificant. The leading mechanism of liver mass recovery after subtotal resection is proliferation of hepatocytes. PMID- 27265143 TI - Rebamipide attenuates Helicobacter pylori CagA-induced self-renewal capacity via modulation of beta-catenin signaling axis in gastric cancer-initiating cells. AB - Rebamipide, a mucosal-protective agent, is used clinically for treatment of gastritis and peptic ulcers induced by Helicobacter pylori (H. pylori) which is associated with increased risk of gastric cancer. Although rebamipide is known to inhibit the growth of gastric cancer cells, the action mechanisms of rebamipide in gastric carcinogenesis remains elusive. Here, we show that rebamipide suppresses H. pylori CagA-induced beta-catenin and its target cancer-initiating cells (C-IC) marker gene expression via upregulation of miRNA-320a and -4496. Rebamipide attenuated in vitro self-renewal capacity of H. pylori CagA-infected gastric C-IC via modulation of miRNA-320a/-4496-beta-catenin signaling axis. Moreover, rebamipide enhanced sensitivity to chemotherapeutic drugs in CagA expressed gastric C-IC. Furthermore, rebamipide suppressed tumor-initiating capacity of gastric C-IC, probably via suppression of CagA-induced C-IC properties. These data provide novel insights for the efficacy of rebamipide as a chemoprotective drug against H. pylori CagA-induced carcinogenic potential. PMID- 27265144 TI - Alterations of cellular redox homeostasis in cultured fibroblast-like renal cells upon exposure to low doses of cytochrome bc1 complex inhibitor kresoxim-methyl. AB - In this paper we elucidate the effects of the cytochrome bc1 inhibitor, strobilurin fungicide kresoxim-methyl, on the redox balance of a mammalian renal cell line. To explore whether mammalian exposure to sub-nephrotoxic concentrations of kresoxim-methyl induces cellular and biochemical mechanisms of toxicity, its effects on cellular viability and, in particular, several parameters related to oxidative stress, mitochondrial respiratory function and apoptosis were examined in fibroblast-like renal Vero cells. Elevation of mitochondrial superoxide generation, together with a concomitant decrease in mitochondrial transmembrane potential was indicative of mitochondrial dysfunction. Losses on antioxidant enzyme activities and GSH, along with increased H2O2 and nitrite release were associated with oxidative stress and induced impaired cellular migration. Raise of intracellular calcium was also observed, while no experimental evidence of apoptosis was found. Our findings suggest that sub-nephrotoxic concentrations of kresoxim-methyl cause perturbation of multiple pathways in renal mammalian cellular redox homeostasis. PMID- 27265145 TI - Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88. AB - Psoriasis is a chronic inflammatory skin disease with excessive activation of toll-like receptors (TLRs), which play important roles in developing psoriasis. Targeting TLR signaling remains a challenge for treating psoriasis. Here, we found that andrographolide (Andro), a small-molecule natural product, alleviated imiquimod- but not interleukin 23 (IL-23)-induced psoriasis in mice with reducing expressions of IL-23 and IL-1beta in the skin. The improvement in imiquimod induced psoriasis by Andro was not observed in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) knockout mice. Furthermore, Andro inhibited mRNA expressions of IL-23, IL-6 and IL-1beta but not CD80 and CD86 in bone-marrow derived dendritic cells (BMDCs) treated with lipopolysaccharide (LPS) in a MAP1LC3B-dependent manner. In addition, Andro inhibited imiquimod-induced mRNA expressions of IL-23, IL-6, IL-1beta, CD80 and CD86 in BMDCs from mice. Interestingly, Andro induced a degradation of myeloid differentiation factor 88 (MyD88) and blocked the recruitment of TNF receptor-associated factor 6 (TRAF6) to MyD88 upon LPS stimulation in BMDCs from mice. Blockade of autophagic proteolysis using NH4Cl or MAP1LC3B(-/-) BMDCs abolished the Andro-induced MyD88 degradation. In conclusion, Andro controls activation of MyD88-dependent cytokines and alleviates psoriasis in mice via inducing autophagic proteolysis of MyD88, which could be a novel strategy to treat psoriasis. PMID- 27265146 TI - Three dimensional Graphene aerogels as binder-less, freestanding, elastic and high-performance electrodes for lithium-ion batteries. AB - In this work it is shown how porous graphene aerogels fabricated by an eco friendly and simple technological process, could be used as electrodes in lithium ion batteries. The proposed graphene framework exhibited excellent performance including high reversible capacities, superior cycling stability and rate capability. A significantly lower temperature (75 degrees C) than the one currently utilized in battery manufacturing was utilized for self-assembly hence providing potential significant savings to the industrial production. After annealing at 600 degrees C, the formation of Sn-C-O bonds between the SnO2 nanoparticles and the reduced graphene sheets will initiate synergistic effect and improve the electrochemical performance. The XPS patterns revealed the formation of Sn-C-O bonds. Both SEM and TEM imaging of the electrode material showed that the three dimensional network of graphene aerogels and the SnO2 particles were distributed homogeneously on graphene sheets. Finally, the electrochemical properties of the samples as active anode materials for lithium ion batteries were tested and examined by constant current charge-discharge cycling and the finding fully described in this manuscript. PMID- 27265148 TI - Blantyre-Oslo Neurosurgery Program. PMID- 27265147 TI - The gender dimensions of social networks and help-seeking behaviors of young adults in Soweto, South Africa. AB - BACKGROUND: Young people constitute a major proportion of the general population and are influenced by a variety of factors, especially in regards to seeking help. An understanding of help-seeking behaviors among young people is important for designing and implementing effective targeted health services. METHODS: We conducted in-depth interviews with 23 young adults aged 21-22 years in Soweto, South Africa, to explore the gender dimensions of social networks and help seeking behaviors. RESULTS: We found that young men had larger peer social networks than young women and that young women's social networks centered on their households. For general health, both young men and young women often sought help from an older, maternal figure. However, for sexual health, young men consulted their group of peers, whereas young women were more likely to seek information from one individual, such as an older female friend or family member. CONCLUSION: These differences in help-seeking behaviors have important implications for the delivery of health information in South Africa and how health promotion is packaged to young men and women, especially for sexual and reproductive health issues. Peer educators might be very effective at conveying health messages for young men, whereas women might respond better to health information presented in a more confidential setting either through community health workers or mHealth technologies. Provision of or linkage to health services that is consistent with young people's health-seeking behavior, such as using peer educators and community health care workers, may increase the reach and utilization of these services among young people. PMID- 27265149 TI - Low-fouling electrospun PLLA films modified with zwitterionic poly(sulfobetaine methacrylate)-catechol conjugates. AB - In this work, we modified a hydrophobic electrospun poly (l-lactic) acid (PLLA) film with poly (sulfobetaine methacrylate) (pSBMA)-catechol conjugates of different molecular weights to improve the biocompatibility of the film. These conjugates were synthesized via atom transfer radical polymerization. They consist of an ultra-low fouling pSBMA zwitterionic polymer with a surface adhesive catechol moiety. X-ray photoelectron spectroscopy, contact angle and scanning electron microscopy experiments were performed to characterize films before and after modification with pSBMA-catechol conjugates. Enzyme-linked immunosorbent and fluorescently-labeled bovine serum albumin were used to study the interactions of proteins with these films. Results showed that low molecular weight zwitterionic pSBMA-catechol conjugates greatly discouraged protein adsorption as shown by use of single protein solutions on PLLA films when the modification was performed in ethanolic Tris-HCl solution. This work offers a convenient and effective method to modify electrospun PLLA films for biomedical applications. STATEMENT OF SIGNIFICANCE: In this work, we report a convenient and effective method to modify electrospun PLLA films using pSBMA-catechol conjugates via "graft-to" for biomedical applications. After pSBMA modification, the PLLA surface becomes hydrophilic with low contact angle and protein adsorption. Results showed that lower molecular weight zwitterionic pSBMA-catechol conjugate led to lower contact angles and better nonfouling properties on PLLA films when the coating was performed in a solution containing ethanol. PMID- 27265150 TI - Degradation and hemostatic properties of polyphosphate coacervates. AB - Sodium polyphosphate is a linear polymer formed from phosphate units linked together by sharing oxygen atoms. Addition of calcium to a solution of sodium polyphosphate results in phase separation and formation of a polyphosphate coacervate best described as a polymeric rich viscoelastic material. Polyphosphate coacervate is an interesting candidate as a biomaterial based on its ability to bind with different cations and to be loaded with drugs. Here, in vitro degradation and hemostatic properties of polyphosphate coacervates are comprehensively evaluated. We show that polyphosphate coacervates degrade and dissolve at a fast rate, losing half of their original mass in a week and transforming to mainly pyrophosphate after 4weeks. This burst dissolution phase happens earlier for the coacervate prepared from very short chain polyphosphate but overall using longer polyphosphate chains does not increase the coacervate longevity significantly. Substitution of Ca with Sr or Ba does not affect the hydrolysis of coacervates but slows down their dissolution into the media. In a whole blood clotting assay, coacervates profoundly decrease the clotting time especially when very long chain polyphosphates are used. While coacervate chain length and divalent cation type were found to significantly affect prothrombin time and thromboplastin time compared to the control, no discernible trends were observed. Platelets adhere in large numbers to coacervates, especially those containing long chain polyphosphate, but the cell morphology observed suggests that they might not to be fully activated. Overall, the long chain polyphosphate coacervate holds a great potential as a resorbable hemostatic agent. STATEMENT OF SIGNIFICANCE: Divalent cation additions to a sodium polyphosphate solution result in polyphosphate coacervates, or highly viscous gel-like materials, having great potential in bio-applications such as drug delivery and hemostasis. As these coacervates degrade in aqueous environments, we undertook a comprehensive evaluation to better understand the impact of polyphosphate chain length and divalent cation substitution on this hydrolytic response in order to better predict degradation behavior in the body. Furthermore, there is great interest in the role of polyphosphates in hemostasis following recent publications showing that platelets secrete polyphosphates upon thrombin stimulation. In this paper, we evaluate the hemostatic potential of polyphosphate coacervates as bulk constructs, demonstrating that indeed these materials hold great potential as a degradable hemostatic agent. PMID- 27265151 TI - Highly efficient intracellular transduction in three-dimensional gradients for programming cell fate. AB - Fundamental behaviour such as cell fate, growth and death are mediated through the control of key genetic transcriptional regulators. These regulators are activated or repressed by the integration of multiple signalling molecules in spatio-temporal gradients. Engineering these gradients is complex but considered key in controlling tissue formation in regenerative medicine approaches. Direct programming of cells using exogenously delivered transcription factors can by pass growth factor complexity but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly using GAG-binding domains to promote cell targeting, and cell penetrating peptides (CPPs) to allow cell entry. Herein we demonstrate that GET can be used in a three dimensional (3D) hydrogel matrix to produce gradients of intracellular transduction of mammalian cells. Using a compartmentalised diffusion model with a source-gel-sink (So-G-Si) assembly, we created gradients of reporter proteins (mRFP1-tagged) and a transcription factor (TF, myogenic master regulator MyoD) and showed that GET can be used to deliver molecules into cells spatio-temporally by monitoring intracellular transduction and gene expression programming as a function of location and time. The ability to spatio temporally control the intracellular delivery of functional proteins will allow the establishment of gradients of cell programming in hydrogels and approaches to direct cellular behaviour for many regenerative medicine applications. STATEMENT OF SIGNIFICANCE: Regenerative medicine aims to reform functional biological tissues by controlling cell behaviour. Growth factors (GFs) are soluble cues presented to cells in spatio-temporal gradients and play important roles programming cell fate and gene expression. The efficient transduction of cells by GET (Glycosaminoglycan-enhanced transducing)-tagged transcription factors (TFs) can be used to by-pass GF-stimulation and directly program cells. For the first time we demonstrate diffusion of GET proteins generate stable protein transduction gradients. We demonstrated the feasibility of creating spatio temporal gradients of GET-MyoD and show differential programing of myogenic differentiation. We believe that GET could provide a powerful tool to program cell behaviour using gradients of recombinant proteins that allow tissue generation directly by programming gene expression with TFs. PMID- 27265152 TI - Rapidly separating microneedles for transdermal drug delivery. AB - The applications of polymer microneedles (MNs) into human skin emerged as an alternative of the conventional hypodermic needles. However, dissolving MNs require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin, which may lead to the low drug delivery efficiency. To address these issues, we introduce rapidly separating MNs that can rapidly deliver drugs into the skin in a minimally invasive way. For the rapidly separating MNs, drug loaded dissolving MNs are mounted on the top of solid MNs, which are made of biodegradable polylactic acid which eliminate the biohazardous waste. These MNs have sufficient mechanical strength to be inserted into the skin with the drug loaded tips fully embedded for subsequent dissolution. Compared with the traditional MNs, rapidly separating MNs achieve over 90% of drug delivery efficiency in 30s while the traditional MNs needs 2min to achieve the same efficiency. With the in vivo test in mice, the micro-holes caused by rapidly separating MNs can heal in 1h, indicating that the rapidly separating MNs are safe for future applications. These results indicate that the design of rapidly separating dissolvable MNs can offer a quick, high efficient, convenient, safe and potentially self-administered method of drug delivery. STATEMENT OF SIGNIFICANCE: Polymer microneedles offer an attractive, painless and minimally invasive approach for transdermal drug delivery. However, dissolving microneedles require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin due to the skin deformation, which may lead to the low drug delivery efficiency. In this work we proposed rapidly separating microneedles which can deliver over 90% of drug into the skin in 30s. The in vitro and in vivo results indicate that the new design of these microneedles can offer a quick, high efficient, convenient and safe method for transdermal drug delivery. PMID- 27265153 TI - Nanoparticles in practice for molecular-imaging applications: An overview. AB - Nanoparticles (NPs) are playing a progressively more significant role in multimodal and multifunctional molecular imaging. The agents like Superparamagnetic iron oxide (SPIO), manganese oxide (MnO), gold NPs/nanorods and quantum dots (QDs) possess specific properties like paramagnetism, superparamagnetism, surface plasmon resonance (SPR) and photoluminescence respectively. These specific properties make them able for single/multi-modal and single/multi-functional molecular imaging. NPs generally have nanomolar or micromolar sensitivity range and can be detected via imaging instrumentation. The distinctive characteristics of these NPs make them suitable for imaging, therapy and delivery of drugs. Multifunctional nanoparticles (MNPs) can be produced through either modification of shell or surface or by attaching an affinity ligand to the nanoparticles. They are utilized for targeted imaging by magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), photo acoustic imaging (PAI), two photon or fluorescent imaging and ultra sound etc. Toxicity factor of NPs is also a very important concern and toxic effect should be eliminated. First generation NPs have been designed, developed and tested in living subjects and few of them are already in clinical use. In near future, molecular imaging will get advanced with multimodality and multifunctionality to detect diseases like cancer, neurodegenerative diseases, cardiac diseases, inflammation, stroke, atherosclerosis and many others in their early stages. In the current review, we discussed single/multifunctional nanoparticles along with molecular imaging modalities. STATEMENT OF SIGNIFICANCE: The present article intends to reveal recent avenues for nanomaterials in multimodal and multifunctional molecular imaging through a review of pertinent literatures. The topic emphasises on the distinctive characteristics of nanomaterial which makes them, suitable for biomedical imaging, therapy and delivery of drugs. This review is more informative of indicative technologies which will be helpful in a way to plan, understand and lead the nanotechnology related work. PMID- 27265154 TI - Knowledge of obstetric danger signs and associated factors among pregnant women in Erer district, Somali region, Ethiopia. AB - BACKGROUND: Knowledge of danger signs of obstetric complications is first step in the appropriate and timely referral to essential obstetric care. Although women's knowledge about the obstetric danger signs is important for improving maternal and child health, little is known about the current knowledge and influencing factors in pastoral community of Ethiopia. This study, therefore, aims to fill this gap by assessing the current level of knowledge and associated factors of pregnant women living in Erer district of Somali region, Ethiopia. METHODS: A community based, cross-sectional study was conducted from April 7 to 21, 2014. The study involved 666 pregnant women residing in the district. Two-stage sampling technique was used to select the study subjects. Data about women's socio-demographic information, reproductive history, knowledge of the danger signs, exposure to media and interventions were collected by interviewer administered questionnaires. A respondent who spontaneously mentioned at least two of the danger signs during each of the three periods was considered knowledgeable; otherwise not. Descriptive, bivariate, then multivariable logistic regression were done. RESULTS: Six hundred thirty two pregnant women were interviewed with a response rate of 94.9 %. Only 98 (15.5 %) respondents were knowledgeable about obstetric danger signs. Urban residence [AOR = 2.43; 95 % CI (1.40, 4.21)], women who had been pregnant five or more times [AOR = 6.65; 95 % CI (2.48, 17.89)] and antenatal care utilization [AOR = 5.44; 95 % CI (3.26, 9.09)] were associated with being knowledgeable about obstetric danger signs during pregnancy, childbirth and postpartum. CONCLUSION: A significant proportion of pregnant women in Erer district do not have knowledge of obstetric danger signs. The implication is that lack of recognition may lead to delay in seeking care. Area of residence, gravidity and antenatal care service utilization are independently associated with the knowledge of women on obstetric danger signs in Erer district, a pastoralist community. Thus, intervention programs aiming to improve women's knowledge about obstetric danger signs and symptoms should consider the factors independently associated. PMID- 27265155 TI - Bilateral sensory deprivation of trigeminal afferent fibres on corticomotor control of human tongue musculature: a preliminary study. AB - Transcranial magnetic stimulation (TMS) has demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs. The aim of this study was to determine whether bilateral local anaesthesia (LA) of the lingual nerve affects the excitability of the tongue motor cortex (MI) as measured by TMS. The effect on MEPs after bilateral LA of the lingual nerve was studied, while the first dorsal interosseous (FDI) muscle served as a control in ten healthy participants. MEPs were measured on the right side of the tongue dorsum in four different conditions: (i) immediately prior to anaesthesia (baseline), (ii) during bilateral LA block of the lingual nerve, (iii) after anaesthesia had subjectively subsided (recovery) and (iv) 3 h after bilateral lingual block injection. MEPs were assessed using stimulus-response curves in steps of 10% of motor threshold (T). Eight stimuli were given at each stimulus level. The amplitudes of the tongue MEPs were significantly influenced by the stimulus intensity (P < 0.001) but not by condition (P = 0.186). However, post hoc tests showed that MEPS were statistically significantly higher during bilateral LA block condition compared with baseline at T + 40%, T + 50% and T + 60% (P < 0.028) and also compared with recovery at T + 60% (P = 0.010) as well as at 3 h after injection at T + 50% and T + 60% (P < 0.029). Bilateral LA block of the lingual nerve seems to be associated with a facilitation of the corticomotor pathways related to the tongue musculature. PMID- 27265156 TI - Corrigendum: Analysing black phosphorus transistors using an analytic Schottky barrier MOSFET model. PMID- 27265157 TI - Cutting-edge capillary electrophoresis characterization of monoclonal antibodies and related products. AB - Out of all categories, monoclonal antibodies (mAbs), biosimilar, antibody-drug conjugates (ADCs) and Fc-fusion proteins attract the most interest due to their strong therapeutic potency and specificity. Because of their intrinsic complexity due to a large number of micro-heterogeneities, there is a crucial need of analytical methods to provide comprehensive in-depth characterization of these molecules. CE presents some obvious benefits as high resolution separation and miniaturized format to be widely applied to the analysis of biopharmaceuticals. CE is an effective method for the separation of proteins at different levels. capillary gel electrophoresis (CGE), capillary isoelectric focusing (cIEF) and capillary zone electrophoresis (CZE) have been particularly relevant for the characterization of size and charge variants of intact and reduced mAbs, while CE MS appears to be a promising analytical tool to assess the primary structure of mAbs and related products. This review will be dedicated to detail the current and state-of-the-art CE-based methods for the characterization of mAbs and related products. PMID- 27265158 TI - A hydrophilic interaction chromatography-tandem mass spectrometry method for amino acid profiling in mussels. AB - A UHPLC-HILIC-tandem MS method has been developed and validated for the quantification of 21 amino acids (20 protein amino acids and cystine) in their free form (FAA) and as protein constituents (total amino acids, TAA) in a rich protein food matrix such as lyophilized mussels (Mytilus galloprovincialis) samples. FAA were analyzed after suspending the samples in the presence of trichloroacetic acid in order to prevent dissolving the proteins, while TAA were determined after acid hydrolysis with 6M HCl in the presence of 4% v/v thioglycolic acid as a reducing agent. In hydrolysed samples 17 amino acids could be determined since tryptophan, cysteine, cystine and asparagine were degraded during acid hydrolysis. Linear regression coefficients (R2) were above 0.99 for all amino acids. Accuracy and precision, expressed as recovery (%) and relative standard deviation (RSD, %) were in acceptable levels, ranging from 78.2 to 123.3% and below 15%, respectively for both FAA and TAA. Uncertainty was also below 12% for FAA and below 22% for TAA. Sensitivity of the method was high with LOD values ranging from 0.003 to 0.034g/100g for FAA and 0.001 to 0.004g/100g for TAA, while LOQ ranged from 0.009 to 0.104g/100g for FAA and 0.002 to 0.011g/100g for TAA. The method proved to be a fast and reliable tool for acquiring information on free and total amino acids profile in high protein content foodstuffs such as mussels. PMID- 27265159 TI - Accuracy of Self-report as a Method of Screening for Lifetime Occurrence of Traumatic Brain Injury Events that Resulted in Hospitalization. AB - BACKGROUND: Traumatic brain injury (TBI) occurs frequently during child and early adulthood, and is associated with negative outcomes including increased risk of drug abuse, mental health disorders and criminal offending. Identification of previous TBI for at-risk populations in clinical settings often relies on self report, despite little information regarding self-report accuracy. This study examines the accuracy of adult self-report of hospitalized TBI events and the factors that enhance recall. METHODS: The Christchurch Health and Development Study is a birth cohort of 1265 children born in Christchurch, New Zealand, in 1977. A history of TBI events was prospectively gathered at each follow-up (yearly intervals 0-16, 18, 21, 25 years) using parental/self-report, verified using hospital records. RESULTS: At 25 years, 1003 cohort members were available, with 59/101 of all hospitalized TBI events being recalled. Recall varied depending on the age at injury and injury severity, with 10/11 of moderate/severe TBI being recalled. Logistic regression analysis indicated that a model using recorded loss of consciousness, age at injury, and injury severity, could accurately classify whether or not TBI would be reported in over 74% of cases. CONCLUSIONS: This research demonstrates that, even when individuals are carefully cued, many instances of TBI will not recalled in adulthood despite the injury having required a period of hospitalization. Therefore, screening for TBI may require a combination of self-report and review of hospital files to ensure that all cases are identified. (JINS, 2016, 22, 717-723). PMID- 27265160 TI - Serum Leptin as a Nutritional Biomarker in Children with Cerebral Palsy. AB - Adequate nutrition is crucial for children with cerebral palsy (CCP). However, conventional nutritional assessments may be inadequate for defining undernourished CCP. Leptin, an adipocyte hormone controlling energy expenditure, could be a useful marker. Objectives of this cross-sectional analytic study were to explore correlations between serum leptin level and nutritional status, anthropometric measurements, and biochemical parameters in 86 CCP (aged 9 +/- 2 years). Subscapular (SST) and triceps (TST) skinfold thicknesses, weight, and calculated height were obtained. Body mass index and weight-for-height (WH) Z scores were calculated. Complete blood count and serum levels of leptin and albumin were collected. CCP were classified as undernourished if their WHZ was < 2 according to the World Health Organization criteria. Correlations between anthropometric measurements, biochemical data, and serum leptin levels were evaluated. From 86 CCP, 11 (12%) children were undernourished, and SST, hemoglobin, and hematocrit were significantly lower. Serum leptin levels of nourished and undernourished CCP were 5.4 +/- 6.2 and 2.9 +/- 1.6 ng/mL (p < 0.001), while the reported value from normal children was 4.9 ng/mL. Serum leptin levels demonstrated a significant correlation with SST and TST (r = 0.83 and 0.72; p < 0.001). Serum leptin was the only marker significantly correlated with WHZ (r = 0.45, p < 0.001) while adjusting for covariates. A serum leptin level of 2.2 ng/mL was the optimal cutoff point for defining adequate nutritional status (WHZ >= -2). The measurement of serum leptin should be included in a care scheme of CCP especially during surgical evaluation. PMID- 27265161 TI - Fetal Bone Formation Is Decreased from Middle Pregnancy to Birth. AB - Fetal bone development is a complex process that is regulated and maintained by minerals, hormones, and growth factors delivered from the mother via the placenta. Various biochemical markers of fetal bone development have been identified. However, many aspects of this process remain unclear. The aim of the study was to measure the activities of serum tartrate-resistant acid phosphatase type 5b (TRACP 5b) as a bone resorption marker and bone alkaline phosphatase (BAP) as a bone formation marker in preterm and term neonates, and to investigate fetal bone development in middle and late pregnancy. The study included 111 neonates (87 preterm and 24 term) born at Dokkyo Medical University Hospital. Neonates with illnesses and maternal diseases were excluded. Serum samples were collected within 3 hours after birth and stored at -80 degrees C. Univariate and multivariate linear regression analyses were performed. The 111 neonates (median birth weight, 1,510 g) were born at a median of 31.3 weeks of gestation, and had TRACP 5b and BAP activities of 10.9 +/- 4.0 U/L and 127.5 +/- 49.2 U/L, respectively. TRACP 5b activity showed a tendency to be higher in term neonates, while BAP activity tended to be lower in term neonates. Importantly, TRACP 5b activity was positively correlated with gestational age and birth weight, and BAP activity was negatively correlated with gestational age, rate of born small-for gestational-age neonates, and birth weight. These results suggest that bone formation during fetal growth is gradually decreased from middle pregnancy to birth, whereas bone resorption is gradually increased. PMID- 27265162 TI - Effect of dietary estrogens from bovine milk on blood hormone levels and reproductive organs in mice. AB - Cows are often milked until 60 d before their next expected calving. Milk from cows in the third trimester of pregnancy contains up to 20 times more estrogens than milk from nonpregnant cows. The aim of this study was to evaluate whether exposure to known doses of estrogens from bovine milk could affect blood hormone levels in mice and influence their reproductive organs. This study was performed with 30 intact male and 30 ovariectomized female mice. Mice of each sex were randomly divided into 3 experimental groups, each with 6 animals of each sex, and a control group with 12 animals of each sex. The first experimental group received 4mL of milk each day from a pregnant cow with natural estrone (E1) and 17beta-estradiol (E2) in concentrations 0.093 and 0.065ng/mL, respectively. The second experimental group received 4mL of the same milk each day, with an added 10ng/mL of both E1 and E2. The third experimental group received 4mL of the same milk each day, with an added 100ng/mL of both E1 and E2. The control group received no milk. After 8 d of treatment, mice were euthanized, blood was collected, and the uteruses, testes, and seminal vesicles were weighed. The results of our study demonstrated that consumption of native milk from a pregnant cow did not affect plasma E1 and E2 levels in either sex; uterine weight in females; or testosterone levels and testes and seminal vesicle weights in males. Similarly, we found no changes in the group that received the milk with an added 10ng/mL of E1 and E2. We did observe elevated plasma estrogens in both sexes, increased uterus weight in females, and decreased plasma testosterone levels in males from the group that received milk with an added 100ng/mL of E1 and E2. However, concentrations in the third group exceeded the physiological concentration of milk estrogens by 1,000 times, so it would be extremely unlikely to find such concentrations in native cow milk. PMID- 27265163 TI - Bacterial counts on teat skin and in new sand, recycled sand, and recycled manure solids used as bedding in freestalls. AB - On modern dairy farms, environmental mastitis pathogens are usually the predominant cause of mastitis, and bedding often serves as a point of exposure to these organisms. The objective of this longitudinal study was to determine bacterial populations of 4 different bedding types [deep-bedded new sand (NES), deep-bedded recycled sand (RS), deep-bedded manure solids (DBMS), and shallow bedded manure solids over foam core mattresses (SBMS)] and of teat skin swabs of primarily primiparous cows housed in a single facility over all 4 seasons. Samples of bedding were collected weekly (n=49wk) from pens that each contained 32 lactating dairy cows. Throughout the length of the same period, composite swabs of teat skin were collected weekly from all cows before and after premilking teat sanitation. Median numbers of streptococci and streptococci-like organisms (SSLO) were >8.6*10(6) cfu/g and >6.9*10(3) cfu/teat swab for all bedding types and teat swabs, respectively. Numbers of SSLO were greatest in samples of SBMS (2.1*10(8) cfu/g) and least in samples of NES (8.6*10(6) cfu/g), RS (1.3*10(7) cfu/g), and DBMS (1.7*10(7) cfu/g). Numbers of gram-negative bacteria in bedding (5.5*10(4) to 1.2*10(7) cfu/g) were fewer than numbers of SSLO (8.6*10(6) to 2.1*10(8) cfu/g). Numbers of coliform bacteria were greatest in samples of DBMS (2.2*10(6) cfu/g) and least in samples of NES (3.6*10(3) cfu/g). In general, the relative number of bacteria on teat skin corresponded to exposure in bedding. Numbers of gram-negative bacteria recovered from prepreparation teat swabs were greatest for cows bedded with DBMS (1.0*10(4) cfu/swab) and RS (2.5*10(3) cfu/swab) and least for cows bedded with NES (5.8*10(2) cfu/swab). Median numbers of coliform and Klebsiella spp. recovered from prepreparation teat swabs were below the limit of detection for all cows except those bedded with DBMS. Numbers of SSLO recovered from prepreparation teat swabs were least for cows bedded with DBMS (6.9*10(3) cfu/swab) and greatest for cows bedded with RS (5.1*10(4) cfu/swab) or SBMS (1.6*10(5) cfu/swab). The numbers of all types of measured bacteria (total gram-negative, coliforms, Klebsiella spp., SSLO) on postpreparation teat swabs were reduced by up to 2.6 logs from numbers of bacteria on prepreparation swabs, verifying effective preparation procedures. Significant correlations between bacterial counts of bedding samples and teat skin swabs were observed for several types of bacteria. As compared with other bedding types, the least amount of gram-negative bacteria were recovered from NES and may indicate that cows on NES have a reduced risk of exposure to pathogens that are typically a cause of clinical mastitis. In contrast, exposure to large numbers of SSLO was consistent across all bedding types and may indicate that risk of subclinical mastitis typically associated with streptococci is not as influenced by bedding type; however, significantly greater numbers of SSLO were found in SBMS than in other bedding types. These findings indicate that use of different bedding types results in exposure to different distributions of mastitis pathogens that may alter the proportion of etiologies of clinical mastitis, although the incidence rate of clinical mastitis did not differ among bedding types. PMID- 27265164 TI - Variation in feeding behavior and milk production among dairy cows when supplemented with 2 amounts of mixed ration in combination with 2 amounts of pasture. AB - Variation in feeding behavior and milk production of grazing dairy cows fed a mixed ration was measured. Experiments were conducted in spring (early lactation) and autumn (late lactation) with 48 Holstein-Friesian dairy cows. Pasture allowance (low vs. high) and amounts of supplement (low vs. high) were applied to determine the effect on variation among cows in feeding behavior and milk production. The experiments investigated 4 dietary treatments in a 2*2 factorial arrangement of treatments. Daily pasture allowances were 15kg of DM/cow per day (low) and 37kg of DM/cow per day (high; to ground level); and 12kg of DM/cow per day (low) and 31kg of DM/cow per day (high; to ground level), for the spring and autumn experiments, respectively. Supplements were offered at 6kg of DM/cow per day (low) and 14kg of DM/cow per day (high); and 6kg of DM/cow per day (low) and 12kg of DM/cow per day (high), for the spring and autumn experiments, respectively. There were 2groups of 6 cows per treatment. All treatments received a partial mixed ration, defined as a total mixed ration fed between periods of grazing that contained wheat grain, corn grain, alfalfa hay, and canola meal. The grain-to-forage ratio of the supplements was 78:22 (DM basis) in both spring and autumn. In both experiments, the pre-experimental period was 14d followed by a 10 d experimental period. The variation among cows within a group in feeding behavior was influenced by the amount of supplement but not the amount of pasture offered. The variation among cows in pasture eating time approximately doubled when the amount of supplement offered increased, indicating that to reduce the variability among cows, supplement feeding management strategies need to be considered. Increasing pasture allowance had no effect on pasture eating time although pasture intake increased as a result of increased grazing intensity compared with the low pasture allowance. However, increasing the amount of supplement in the partial mixed ration feeding system reduced pasture eating time by 51min/cow per day. PMID- 27265165 TI - Changes in fermentation and biohydrogenation intermediates in continuous cultures fed low and high levels of fat with increasing rates of starch degradability. AB - Excessive levels of starch in diets for lactating dairy cattle is a known risk factor for milk fat depression, but little is known about how this risk is affected by differences in rates of starch degradability (Kd) in the rumen. The objective of this study was to compare accumulation of biohydrogenation intermediates causing milk fat depression, including conjugated linoleic acid (CLA), when corn with low or high Kd were fed to continuous cultures. Diets contained (dry matter basis) 50% forage (alfalfa pellets and grass hay) and 50% concentrate, with either no added fat (LF) or 3.3% added soybean oil (HF). Within both the LF and HF diets, 3 starch degradability treatments were obtained by varying the ratio of processed (heat and pressure treatments) and unprocessed corn sources, giving a total of 6 dietary treatments. Each diet was fed to dual flow continuous fermenters 3 times a day at 0800, 1600, and 2400h. Diets were fed for four 10-d periods, with 7d for adaptation and 3d for sample collection. Orthogonal contrasts were used in the GLIMMIX procedure of SAS to test the effects of fat, starch degradability, and their interaction. Acetate and acetate:propionate were lower for HF than for LF but daily production of trans-10 18:1 and trans-10,cis-12 CLA were higher for HF than for LF. Increasing starch Kd from low to high increased culture pH, acetate, and valerate but decreased butyrate and isobutyrate. Changes in biohydrogenation intermediates (expressed as % of total isomers) from low to high starch Kd included reductions in trans-11 18:1 and cis-9,trans-11 CLA but increases in trans-10 18:1 and trans-10,cis-12 CLA. The results show that increasing the starch Kd in continuous cultures while holding starch level constant causes elevation of biohydrogenation intermediates linked to milk fat depression. PMID- 27265166 TI - Short communication: Survival of Mycobacterium avium ssp. paratuberculosis in tissues of cows following low-dose exposure to electron beam irradiation. AB - This investigation was designed to determine the effects of low-dose electron beam irradiation on the survival of Mycobacterium avium ssp. paratuberculosis in tissue samples collected at necropsy from clinically affected cows. Mycobacterium avium ssp. paratuberculosis was isolated from the ileum and ileocecal valve of one cow and from the ileum of another cow irradiated at 4.0 kGy, but was not isolated from the ileum, ileocecal valve, or mesenteric lymph node of 11 other cows irradiated at 4 kGy. PMID- 27265167 TI - Short communication: ELISA system for screening of bovine mastitis caused by Prototheca zopfii. AB - Prototheca zopfii is an achlorophyllic alga that causes bovine mastitis, resulting in a reduction in milk production and the secretion of thin, watery milk with white flakes. This study evaluated the use of an ELISA system for distinguishing cows with mastitis due to P. zopfii genotype 2 from healthy cows and cows with chronic candidal mastitis. We also investigated the transitional changes of specific antibody titers in healthy cows injected with inactivated P. zopfii genotype 2 cells. The ELISA system exhibited the highest sensitivity (94%) and specificity (100%) for chronic protothecal mastitis when the positive cutoff value was set at 43.4 ELISA units. Anti-protothecal IgG titers were positive in all cows after they were inoculated with inactivated P. zopfii genotype 2 cells. These results indicated that ELISA detection of anti-protothecal IgG in serum provided specificity and sensitivity sufficient for diagnosing protothecal mastitis. Thus, an ELISA system incorporating this specific antiserum is expected to be valuable for definitive field-based diagnosis of bovine mastitis due to P. zopfii genotype 2. PMID- 27265168 TI - Short communication: Effect of maternal heat stress in late gestation on blood hormones and metabolites of newborn calves. AB - Maternal heat stress alters immune function of the offspring, as well as metabolism and future lactational performance, but its effect on the hormonal and metabolic responses of the neonate immediately after birth is still not clear. The objective of this study was to investigate the blood profiles of hormones and metabolites of calves born to cows that were cooled (CL) or heat-stressed (HS) during the dry period. Within 2 h after birth, but before colostrum feeding, blood samples were collected from calves [18 bulls (HS: n=10; CL: n=8) and 20 heifers (HS: n=10; CL: n=10)] born to CL or HS dry cows, and hematocrit and plasma concentrations of total protein, prolactin, insulin-like growth factor-I, insulin, glucose, nonesterified fatty acid, and beta-hydroxybutyrate were measured. Compared with CL, HS calves had lower hematocrit and tended to have lower plasma concentrations of insulin, prolactin, and insulin-like growth factor I. However, maternal heat stress had no effect on plasma levels of total protein, glucose, fatty acid, and beta-hydroxybutyrate immediately after birth. These results suggest that maternal heat stress desensitizes a calf's stress response and alters the fetal development by reducing the secretion of insulin-like growth factor-I, prolactin, and insulin. PMID- 27265169 TI - Optimization of protein fractionation by skim milk microfiltration: Choice of ceramic membrane pore size and filtration temperature. AB - The objective of this study was to investigate how ceramic membrane pore size and filtration temperature influence the protein fractionation of skim milk by cross flow microfiltration (MF). Microfiltration was performed at a uniform transmembrane pressure with constant permeate flux to a volume concentration factor of 2.5. Three different membrane pore sizes, 0.05, 0.10, and 0.20um, were used at a filtration temperature of 50 degrees C. Furthermore, at pore size 0.10um, 2 different filtration temperatures were investigated: 50 and 60 degrees C. The transmission of proteins increased with increasing pore size, giving the permeate from MF with the 0.20-um membrane a significantly higher concentration of native whey proteins compared with the permeates from the 0.05- and 0.10-um membranes (0.50, 0.24, and 0.39%, respectively). Significant amounts of caseins permeated the 0.20-um membrane (1.4%), giving a permeate with a whitish appearance and a casein distribution (alphaS2-CN: alphaS1-CN: kappa-CN: beta-CN) similar to that of skim milk. The 0.05- and 0.10-um membranes were able to retain all caseins (only negligible amounts were detected). A permeate free from casein is beneficial in the production of native whey protein concentrates and in applications where transparency is an important functional characteristic. Microfiltration of skim milk at 50 degrees C with the 0.10-um membrane resulted in a permeate containing significantly more native whey proteins than the permeate from MF at 60 degrees C. The more rapid increase in transmembrane pressure and the significantly lower concentration of caseins in the retentate at 60 degrees C indicated that a higher concentration of caseins deposited on the membrane, and consequently reduced the native whey protein transmission. Optimal protein fractionation of skim milk into a casein-rich retentate and a permeate with native whey proteins were obtained by 0.10-um MF at 50 degrees C. PMID- 27265170 TI - Influences of season, parity, lactation, udder area, milk yield, and clinical symptoms on intramammary infection in dairy cows. AB - The aim of this study was to evaluate the influences of season, parity, lactation, udder area, milk yield, and clinical symptoms on bacterial intramammary infection (IMI) in dairy cows. A total of 2,106 mastitis pathogens in 12 species were isolated from 125 dairy farms distributed in 30 different cities in China, and the information about these factors was recorded at the same time. Mastitis pathogens were isolated from 63.43% of the milk samples, whereas Streptococcus agalactiae accounted for 38.61% of all pathogens, followed by Str. dysgalactiae (28.16%), Staphylococcus aureus (19.10%), Escherichia coli (6.90%), and other pathogens (7.23%). According to our investigation, IMI was more common in spring with the isolation rate of pathogens at 81.04%, and lowest in winter (52.34%). Cows were more likely to be infected by environmental pathogens (E. coli or Str. uberis) in summer, in rear quarters and in cows with higher daily milk yield or lower somatic cell count. In addition, Str. dysgalactiae exhibited a higher prevalence with increased parity. Different clinical symptoms of quarters with bacterial IMI were seen in this study, and mastitis pathogens were isolated from healthy quarters. PMID- 27265171 TI - Acid-responsive properties of fibrils from heat-induced whey protein concentrate. AB - The heat-induced fibrils of whey protein concentrate (WPC) have demonstrated an acid-responsive property; that is, the fibrils went through formation depolymerization-reformation as pH was adjusted to 1.8, 6.5, and back to 1.8. We investigated the microstructure, driving force, and thermal stability of 3.0% (wt) WPC nanofibrils adjusted between pH 6.5 and 1.8 twice. The results showed that the nanofibrils had acid-responsive properties and good thermal stability after reheating for 10h at 90 degrees C and adjusting pH from 1.8 to 6.5 to 1.8. The content of WPC fibril aggregates was not much different with the prolongation of heating times during pH variation. Although the nanofibrils' structure could be destroyed only by changing the pH, the essence of this destruction might only form fiber fragments, polymers that would restore a fibrous structure upon returning to pH 1.8. A described model for the acid-responsive assembly of fibrils of WPC was proposed. The fibrils went through formation-depolymerization reformation by weaker noncovalent interactions (surface hydrophobicity) as pH changed from 1.8 to 6.5 back to 1.8. However, the fibrils lost the acid responsive properties because much more S-S (disulfide) formation occurred when the solution was adjusted to pH 6.5 and reheated. Meanwhile, fibrils still possessed acid-responsive properties when reheated at pH 1.8, and the content of fibrils slightly increased with a further reduction of alpha-helix structure. PMID- 27265172 TI - Effects of 3 sequestering agents on milk aflatoxin M1 concentration and the performance and immune status of dairy cows fed diets artificially contaminated with aflatoxin B1. AB - This study examined whether adding 3 mycotoxin-sequestering agents to diets contaminated with aflatoxin B1 (AFB1) would reduce milk aflatoxin M1 (AFM1) concentration, and improve the performance and alter immune status of dairy cows. Fifteen lactating dairy cows were used in an experiment with an incomplete crossover design including four 28-d periods. Treatments included a control diet (C), a toxin diet (T; 1,725ug of AFB1/head per day; 75ug/kg), and diets containing the toxin and 20g/head per day of a proprietary mixture of Saccharomyces cerevisiae fermentation product containing a low (SEQ1) or high (SEQ2) dose of a chlorophyll-based additive, or a low dose of the chlorophyll based additive and sodium bentonite clay (SEQ3). Sequestering agents were top dressed on the total mixed ration (TMR) daily in each period, and AFB1 was dosed orally in gelatin capsules before the TMR was fed on d 21 to 25. Milk was sampled twice daily on d 20 to 28 and plasma was sampled on d 20 and 25. Sequestering agents did not affect milk AFM1 concentration during the toxin-dosing period. However, after AFB1 was withdrawn, the sequestering agents reduced the time required (24 vs. 48h) to reduce the milk AFM1 concentration below the Food and Drug Administration action level of 0.5ug/kg. Feeding T instead of C tended to reduce milk and fat-corrected milk yields, but feeding SEQ1 prevented these effects. Red blood cell count and hemoglobin concentration were reduced by feeding T instead of C, but not by feeding SEQ1, SEQ2, or SEQ3. The mean fluorescence intensity of antibody staining for 2 leukocyte adhesion molecules, L selectin (CD62L) and beta-integrin (CD18), tended to be greatest when SEQ1 and SEQ3 were fed. Plasma acid-soluble protein concentration was decreased by feeding SEQ1, SEQ2, and SEQ3 instead of T. Sequestering agents had no effect on milk AFM1 concentration, but they reduced the time required to reduce milk AFM1 concentration to a safe level after withdrawal of AFB1 from the diet. Only SEQ1 prevented the adverse effects of AFB1 on milk and fat-corrected milk yields. PMID- 27265173 TI - Inhibitory effect of liposome-entrapped lemongrass oil on the growth of Listeria monocytogenes in cheese. AB - Listeria monocytogenes infection in dairy products is of mounting public concern. To inhibit bacterial growth, we engineered stimuli-responsive liposomes containing lemongrass oil for this study. The controlled release of liposome entrapped lemongrass oil is triggered by listerolysin O, secreted by L. monocytogenes. We investigated the antibiotic activities of lemongrass oil liposomes against L. monocytogenes in cheese. We also assessed their possible effects on the quality of the cheese. Liposomes containing lemongrass oil (5.0mg/mL) presented the optimal polydispersity index (0.246), zeta-potential ( 58.9mV) and entrapment efficiency (25.7%). The liposomes displayed satisfactory antibiotic activity against L. monocytogenes in cheese over the storage period at 4 degrees C. We observed no effects on the physical and sensory properties of the cheese after the liposome treatment. PMID- 27265174 TI - Randomized clinical trial of a calcium supplement for improvement of health in dairy cows in early lactation. AB - Prophylactic Ca supplementation immediately after calving is a common strategy to prevent clinical and subclinical hypocalcemia in parturient dairy cows. The objective of this study was to evaluate the effect of prophylactic administration of an injected Ca supplement on blood Ca concentration at 24 and 48h after treatment, incidence risk of clinical disease and culling, milk production in early lactation, and probability of pregnancy at first insemination. Cows without signs of visible milk fever (n=984) from 7 farms were blocked by parity and randomly assigned to receive either Ca gluconate (35% wt/vol) in combination with Ca glucoheptonate (10% wt/vol; TheraCalcium, Vetoquinol Canada Inc., Lavaltrie, Quebec) or a placebo (medication vehicle solution with no Ca) at first contact with each cow after calving and again 12 to 24h later. Each dose was 120mL injected subcutaneously over 2 sites. Total serum Ca concentration (tCa) was measured from coccygeal blood samples before (time 0) and 24 and 48h after first treatment in a subsample of cows (n=129). Blood beta-hydroxybutyrate concentrations were measured from all cows twice between 3 and 16d in milk at weekly visits and cows were evaluated for vaginal discharge once between 28 and 42d in milk. Disease events, production data from the first 3 Dairy Herd Improvement milk tests, reproduction, and culling data were collected from each herd. For cows that had received 1 injection of Ca before the blood sample at 24h (n=95), tCa was significantly higher in the treated cows: mean +/- standard error, 2.03+/-0.03 versus 1.90+/-0.03mmol/L, accounting for tCa at time of enrollment and a treatment by tCa at enrollment interaction. At 48h, no significant difference was found in tCa between treatment and control (mean +/- SE, 2.12+/-0.02 and 2.10+/-0.03mmol/L, respectively). Cows treated with the Ca product were significantly less likely to have received intravenous, subcutaneous, or oral supplemental Ca for exhibiting clinical signs of hypocalcemia than control cows (5.0 vs. 8.4%). No effect was found of treatment on retained placenta, metritis, hyperketonemia, prevalence of purulent vaginal discharge, culling from the herd, early lactation production, probability of pregnancy to first artificial insemination, or time to pregnancy. With this subcutaneous prophylactic Ca treatment regimen, blood Ca levels were temporarily increased at 24h after treatment, but no effect was observed of supplemental Ca on the risk of disease or culling, milk production, or reproductive performance. PMID- 27265175 TI - Rapid quantification of casein in skim milk using Fourier transform infrared spectroscopy, enzymatic perturbation, and multiway partial least squares regression: Monitoring chymosin at work. AB - In this study, we introduce enzymatic perturbation combined with Fourier transform infrared (FTIR) spectroscopy as a concept for quantifying casein in subcritical heated skim milk using chemometric multiway analysis. Chymosin is a protease that cleaves specifically caseins. As a result of hydrolysis, all casein proteins clot to form a creamy precipitate, and whey proteins remain in the supernatant. We monitored the cheese-clotting reaction in real time using FTIR and analyzed the resulting evolution profiles to establish calibration models using parallel factor analysis and multiway partial least squares regression. Because we observed casein-specific kinetic changes, the retrieved models were independent of the chemical background matrix and were therefore robust against possible covariance effects. We tested the robustness of the models by spiking the milk solutions with whey, calcium, and cream. This method can be used at different stages in the dairy production chain to ensure the quality of the delivered milk. In particular, the cheese-making industry can benefit from such methods to optimize production control. PMID- 27265176 TI - Effects of the conjugation of whey proteins with gellan polysaccharides on surfactant-induced competitive displacement from the air-water interface. AB - Whey proteins can be used to stabilize foams and emulsions against coalescence because of their ability to form viscoelastic films at the interface that resist film rupture on collision between colloidal particles. However, whey proteins are competitively displaced from the interface if small-molecule surfactants are added, leading to destabilization of the entire system. This is because surfactants are more effective in molecular packing at the interface, and they lower interfacial tension to a greater degree than whey proteins do, but their interfacial films are poor in viscoelasticity. We hypothesized that whey proteins would become more resistant to surfactant-induced competitive displacement if they were conjugated with network-forming polysaccharides. The protein moiety of the conjugate would be expected to enable its adsorption to the interface, and the polysaccharide moiety would be expected to form self-assembled networks, strengthening the interfacial film as a whole. In this study, whey proteins were conjugated with gellan polysaccharides using the Maillard reaction. Atomic force microscopy images of interfacial films formed by the whey protein-gellan conjugate at the air-water interface and transferred onto mica sheets using the Langmuir-Blodgett method revealed that gellan did form self-assembled networks at the interface and that interfacial films also contained a large number of unconjugated whey protein molecules. Following the addition of a small-molecule surfactant (Tween 20) to the sub-phase, surface pressure increased, indicating spontaneous adsorption of surfactants to the interface. Atomic force microscopy images showed decreases in interfacial area coverage by whey proteins as surface pressure increased. At a given surface pressure, the interfacial area coverage by whey protein-gellan conjugates was greater than coverage by unconjugated whey proteins, confirming that whey proteins became more resistant to surfactant induced displacement after conjugation with gellan. Furthermore, gellan molecules added to the sub-phase after the formation of a monolayer of whey proteins at the air-water interface did not adsorb to the interfacial protein film. These results provide a molecular basis for designing interfacial structures to enhance the stability of colloidal systems. PMID- 27265177 TI - Evaluation of milk cathelicidin for detection of dairy sheep mastitis. AB - Mastitis due to intramammary infections is one of the most detrimental diseases in dairy sheep farming, representing a major cause of reduced milk productions and quality losses. In particular, subclinical mastitis presents significant detection and control problems, and the availability of tools enabling its timely, sensitive, and specific detection is therefore crucial. We have previously demonstrated that cathelicidins, small proteins implicated in the innate immune defense of the host, are specifically released in milk of mastitic animals by both epithelial cells and neutrophils. Here, we describe the development of an ELISA for milk cathelicidin and assess its value against somatic cell counts (SCC) and bacteriological culture for detection of ewe mastitis. Evaluation of the cathelicidin ELISA was carried out on 705 half-udder milk samples from 3 sheep flocks enrolled in a project for improvement of mammary health. Cathelicidin was detected in 35.3% of milk samples (249/705), and its amount increased with rising SCC values. The cathelicidin-negative (n=456) and cathelicidin-positive (n=249) sample groups showed a clear separation in relation to SCC, with median values of 149,500 and 3,300,000 cells/mL, respectively. Upon bacteriological culture, 20.6% (145/705) of the milk samples showed microbial growth, with coagulase-negative staphylococci being by far the most frequent finding. A significant proportion of all bacteriologically positive milk samples were positive for cathelicidin (110/145, 75.9%). Given the lack of a reliable gold standard for defining the true disease status, sensitivity (Se) and specificity (Sp) of the cathelicidin ELISA were assessed by latent class analysis against 2 SCC thresholds and against bacteriological culture results. At an SCC threshold of 500,000 cells/mL, Se and Sp were 92.3 and 92.3% for cathelicidin ELISA, 89.0 and 94.9% for SCC, and 39.4 and 93.6% for bacteriological culture, respectively. At an SCC threshold of 1,000,000 cells/mL, Se and Sp were 93.3 and 91.9% for cathelicidin ELISA, 80.0 and 97.1% for SCC, and 39.4 and 93.5% for bacteriology, respectively. In view of the results obtained in this study, the measurement of cathelicidin in milk by ELISA can provide added Se while maintaining a high Sp and may therefore improve detection of subclinical mastitis. PMID- 27265178 TI - Randomized noninferiority field trial comparing 2 first-generation cephalosporin products at dry off in quarters receiving an internal teat sealant in dairy cows. AB - The study objective was to compare 2 commercial dry cow mastitis products at the quarter level, with concurrent internal teat sealant application, evaluating the cure risk difference, odds of a cure, odds of a new intramammary infection (NIMI) during the dry period, and risk for a clinical mastitis (CM) case between calving and 60d in milk (DIM). A total of 590 cows (2,360 quarters) from 8 commercial dairy herds in Italy were enrolled and randomized to 1 of the 2 treatments at dry off: Cefovet A (CF; 250mg of cephazoline; Merial Italia SpA, Milan, Italy), and Cepravin (CP; 250mg of cephalonium dehydrate MSD Animal Health Srl, Segrate, Italy). Quarter milk samples were collected before dry cow therapy treatment at dry off, 2 to 9 DIM, and 10 to 17 DIM. Quarter milk samples from CM cases were collected during the first 60 DIM. Noninferiority analysis was used to evaluate the effect of treatment on the risk difference of a bacteriological cure during the dry period, the primary outcome. The odds of cure, developing a NIMI during the dry period, and the risk of a CM event within 60 DIM were evaluated with multivariable logistic regression and hazard analysis, respectively. The overall crude quarter-level prevalence of NIMI at dry off was 15.3%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative staphylococci. Noninferiority analysis showed no effect of treatment on the risk difference for a cure between dry off and both postpartum samples, difference was 0.013. The least squares means from the multivariable model evaluating the odds of cure was 94% for CF and 95%for CP. We observed no effect of treatment on the odds for the presence of a NIMI at 2 to 9 DIM (least squares means: CF=0.09 and CP=0.07), nor did we note a difference in risk of experiencing a CM event between calving and 60 DIM (hazard ratio=0.8). In conclusion, no difference was observed between the 2 products evaluated when assessing the aforementioned outcomes in quarters also receiving an internal teat sealant. PMID- 27265179 TI - Effects of grazing cow diet on volatile compounds as well as physicochemical and sensory characteristics of 12-month-ripened Montasio cheese. AB - The aim of this study was to evaluate the effects of pasture type and cow feeding supplementation level on a 12-mo-ripened Montasio protected designation of origin (PDO) cheese, which is one of the most important PDO cheeses produced in northeast Italy. Cheeses were characterized for volatile compounds, color, mechanical variables, and sensory descriptors. Pasture type significantly affected most of the instrumental variables considered and, as a consequence, sensory properties were affected as well. Cheeses from the pasture characterized by a nutrient-rich vegetation type were higher in protein and lower in fat content. Furthermore, such cheeses, evaluated by a sensory panel, were more intense in color with a more pungent and less cow-like odor, in agreement with what found through instrumental analyses. Supplementation level resulted in less pronounced effects, limited to volatile compounds and texture properties, which were not detected by sensory analysis. The characterization of the 12-mo ripened Montasio cheese reported here is an important step for the valorization of this PDO product. PMID- 27265180 TI - A sacrificial millipede altruistically protects its swarm using a drone blood enzyme, mandelonitrile oxidase. AB - Soldiers of some eusocial insects exhibit an altruistic self-destructive defense behavior in emergency situations when attacked by large enemies. The swarm forming invasive millipede, Chamberlinius hualienensis, which is not classified as eusocial animal, exudes irritant chemicals such as benzoyl cyanide as a defensive secretion. Although it has been thought that this defensive chemical was converted from mandelonitrile, identification of the biocatalyst has remained unidentified for 40 years. Here, we identify the novel blood enzyme, mandelonitrile oxidase (ChuaMOX), which stoichiometrically catalyzes oxygen consumption and synthesis of benzoyl cyanide and hydrogen peroxide from mandelonitrile. Interestingly the enzymatic activity is suppressed at a blood pH of 7, and the enzyme is segregated by membranes of defensive sacs from mandelonitrile which has a pH of 4.6, the optimum pH for ChuaMOX activity. In addition, strong body muscle contractions are necessary for de novo synthesis of benzoyl cyanide. We propose that, to protect its swarm, the sacrificial millipede also applies a self-destructive defense strategy-the endogenous rupturing of the defensive sacs to mix ChuaMOX and mandelonitrile at an optimum pH. Further study of defensive systems in primitive arthropods will pave the way to elucidate the evolution of altruistic defenses in the animal kingdom. PMID- 27265182 TI - Serum alpha-linolenic and other omega-3 fatty acids, and risk of disabling dementia: Community-based nested case-control study. AB - BACKGROUND & AIMS: It has been hypothesized that omega-3 polyunsaturated fatty acids have anti-atherosclerotic and neuronal protective functions and may benefit prevention of dementia, but the epidemiological evidence, especially for alpha linolenic acid, is quite limited. The aim of this study was to examine whether serum omega-3 polyunsaturated fatty acids are associated with risk of dementia. METHODS: We performed an intracohort case-control study nested in a community based cohort, the Circulatory Risk in Communities Study, involving 7586 Japanese individuals aged 40-74 years at the baseline period of 1984-1994. Omega-3 polyunsaturated fatty acid constituents (alpha-linolenic, eicosapentaenoic, and docosahexaenoic acids) in serum total lipid were measured in 315 cases of incident disabling dementia in the above-mentioned cohort between 1999 and 2004, and in 630 controls whose age, sex, area, and baseline year were matched with the cases. RESULTS: As we had postulated, serum alpha-linolenic acid was inversely associated with risk of disabling dementia: the multivariate odds ratios (95% confidence intervals) were 0.57 (0.39-0.85), 0.51 (0.34-0.76), and 0.61 (0.41 0.90) for persons with the second, third, and highest quartiles of serum alpha linolenic acid, respectively, as compared with the lowest quartile (P for trend = 0.01). Associations of other omega-3 fatty acids with disabling dementia were not statistically significant. CONCLUSIONS: Serum alpha-linolenic acid was inversely associated with risk of disabling dementia. Although the causality needs to be confirmed by randomized control trials, we identified serum alpha-linolenic acid as a biomarker that predicts future dementia. PMID- 27265181 TI - Anabolic effects of leucine-rich whey protein, carbohydrate, and soy protein with and without beta-hydroxy-beta-methylbutyrate (HMB) during fasting-induced catabolism: A human randomized crossover trial. AB - BACKGROUND: Protein-rich beverages are widely used clinically to preserve muscle protein and improve physical performance. Beverages with high contents of leucine or its keto-metabolite beta-hydroxy-beta-methylbutyrate (HMB) are especially anabolic in muscle, but it is uncertain whether this also applies to catabolic conditions such as fasting and whether common or separate intracellular signaling cascades are involved. OBJECTIVE: To compare a specific leucine-rich whey protein beverage (LWH) with isocaloric carbohydrate- (CHO), soy protein (SOY), and soy protein +3 g HMB (HMB) during fasting-induced catabolic conditions. DESIGN: Eight healthy lean male subjects underwent four interventions (LWH, CHO, SOY, and HMB) using a randomized crossover design. Each trial included a 36 h fast and consisted of a 3 h basal fasting period and a 4 h 'sipping' period. RESULTS: Forearm net balances of phenylalanine (NBphe, measure of net protein loss) improved for all groups (p < 0.05), but more prominently so for LWH and HMB compared with SOY (p < 0.05). Muscle protein phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets eukaryotic translation factor 4E binding protein 1 (4EBP1) and ribosomal S6 kinase 1 (S6) were distinctly increased during LWH consumption (p < 0.05). The ratio between autophagy protein microtubule-associated protein 1 light chain-3beta II and I (LC3II/LC3I, a measure of autophagy activity) was decreased during LWH and SOY intake compared with the fasting period (p < 0.05). CONCLUSION: LWH and HMB have superior anabolic effects on muscle protein kinetics after 36 h of fasting, and LWH distinctly activates the mTOR pathway. These novel findings suggest that leucine rich whey protein and/or HMB are specifically beneficial during fasting-induced catabolic conditions. PMID- 27265183 TI - Is mortality in Cushing's disease reversible with remission? PMID- 27265185 TI - Heritable Thrombophilia and Pregnancy Associated Thrombosis. PMID- 27265184 TI - Mortality in patients with Cushing's disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study. AB - BACKGROUND: No agreement has been reached on the long-term survival prospects for patients with Cushing's disease. We studied life expectancy in patients who had received curative treatment and whose hypercortisolism remained in remission for more than 10 years, and identified factors determining their survival. METHODS: We did a multicentre, multinational, retrospective cohort study using individual case records from specialist referral centres in the UK, Denmark, the Netherlands, and New Zealand. Inclusion criteria for participants, who had all been in studies reported previously in peer-reviewed publications, were diagnosis and treatment of Cushing's disease, being cured of hypercortisolism for a minimum of 10 years at study entry, and continuing to be cured with no relapses until the database was frozen or death. We identified the number and type of treatments used to achieve cure, and used mortality as our primary endpoint. We compared mortality rates between patients with Cushing's disease and the general population, and expressed them as standardised mortality ratios (SMRs). We analysed survival data with multivariate analysis (Cox regression) with no corrections for multiple testing. FINDINGS: The census dates on which the data were frozen ranged from Dec 31, 2009, to Dec 1, 2014. We obtained data for 320 patients with 3790 person-years of follow-up from 10 years after cure (female:male ratio of 3:1). The median patient follow-up was 11.8 years (IQR 17 26) from study entry and did not differ between countries. There were no significant differences in demographic characteristics, duration of follow-up, comorbidities, treatment number, or type of treatment between women and men, so we pooled data from both sexes for survival analysis. 51 (16%) of the cohort died during follow-up from study entry (10 years after cure). Median survival from study entry was similar for women (31 years; IQR 19-38) and men (28 years; 24 42), and about 40 years (IQR 30-48) from remission. The overall SMR for all-cause mortality was 1.61 (95% CI 1.23-2.12; p=0.0001). The SMR for circulatory disease was increased at 2.72 (1.88-3.95; p<0.0001), but deaths from cancer were not higher than expected (0.79, 0.41-1.51). Presence of diabetes, but not hypertension, was an independent risk factor for mortality (hazard ratio 2.82, 95% CI 1.29-6.17; p=0.0095). We noted a step-wise reduction in survival with increasing number of treatments. Patients cured by pituitary surgery alone had long-term survival similar to that of the general population (SMR 0.95, 95% CI 0.58-1.55) compared with those who were not (2.53, 1.82-3.53; p<0.0001). INTERPRETATION: Patients with Cushing's disease who have been in remission for more than 10 years are at increased risk of overall mortality compared with the general population, particularly from circulatory disease. However, median survival from cure is excellent at about 40 years of remission. Treatment complexity and an increased number of treatments, reflecting disease that is more difficult to control, appears to negatively affect survival. Pituitary surgery alone is the preferred treatment to secure an optimum outcome, and should be done in a centre of surgical excellence. FUNDING: None. PMID- 27265186 TI - The Importance of Serum Transferrin Receptor and TfR-F Index in the Diagnosis of Iron Deficiency Accompanied by Acute and Chronic Infections. AB - This study evaluated the diagnostic superiority of serum transferrin receptor (sTfR) measurement to other laboratory tests performed for the determination of iron deficiency caused by chronic disease (CD). Study group consisted of 114 anemic patients allocated into 3 groups at the pediatrics clinic of Ankara University, Faculty of Medicine and 32 healthy pediatric subjects as the control group. sTfR value ranged between 11.00 nmol/L and 26.20 nmol/L for the control group. However, it was 61.29 +/- 39.33 nmol/L in iron deficiency anemia (IDEA) group, consisting of 51 patients. While there was a significant positive correlation between sTfR and Hb, MCV, serum iron, ferritin levels, there was a significantly inverse correlation between sTfR with RDW in the IDEA group. Mean sTfR value was found 47.05 +/- 28.07 nmol/L in the acute infection (AI) group consisting of 22 patients, 39.31 +/- 26.16 nmol/L in the CD group with 41 patients. Statistically significant difference was found between sTfR of IDEA group and sTfR of the AI group, though accompanied by iron deficiency. These findings showed that sTfR levels were suppressed. That all hematologic parameters including ferritin and sTfR of all patients in the CD group were heterogenous and revealed both normal and abnormal values was noteworthy. To determine the existence of accompanying iron deficiency, sTfR values above 28.10 nmol/L were chosen. It was concluded that the diagnosis of these patients was not possible without sTfR measurement. TfR-F index (sTfR/log ferritin) was found 97.72 +/- 108.81 in the IDEA group, 52.16 +/- 66.25 in the AI group, and 24.36 +/- 43.00 in the CD group (p< 0.001). TfR-F index values of the chronic disease anemia group (ACD) and the iron deficiency anemia group accompanied by chronic disease (COMBI) were compared. The difference between these two groups was statistically significant (p< 0.001). Thus, TfR-F index proved useful in evaluating the changes of iron metabolism and reducing iron necessities in patients. PMID- 27265187 TI - Detection of Epstein Barr Virus in Hodgkin's Disease in Trakya Region of Turkey; by in Situ Hybridization. AB - The relation of Epstein-Barr virus (EBV) and Hodgkin's disease (HD) has been suggested by serologic, epidemiological and molecular biologic studies. According to these studies the incidence of EBV in HD is high. In the present study, the EBV association with HD in Trakya Region of Turkey was investigated. We investigated the presence of EBV in 44 cases of HD. Fluorescein-labelled antisense EBV (EBER-RNA) was performed by in situ hybridization. There were 28 males and 16 females, with a mean age of 40 years (range 4-80 years). Histological subtypes included nodular sclerosis Hodgkin's disease (NSHD) in 18 (40.9%), mixed cellularity (MCHD) in 16 (36.4%), lymphocyte predominance (LPHD) in 7 (15.9%), and lymphocyte depletion (LDHD) in 3 (6.8%). EBV was expressed in 30 cases (68.2%). High EBV association was found with mixed cellularity 75% and nodular sclerosis 72.2%. In lymphocyte predominance and in lymphocyte depletion cases the EBV positivity was 57.1% and 33.3%, respectively. All of 7 cases, younger than 15 years old, were positive for EBV. HD in Trakya Region showed a high association with EBV as in developing countries. Our findings suggest that EBV plays an important role in the pathogenesis of HD in Turkey. PMID- 27265188 TI - Radiographic Findings in Hyperimmunoglobulin E Syndrome. AB - The aim of this study is to demonstrate the spectrum of radiologic findings of hyperimmunoglobulin E (hyper- IgE) syndrome that is relatively rare in adults. We describe the imaging findings of this rare disease in five patients. The study group consisted of 4 men and 1 woman. The final diagnosis was made according to laboratory findings in all cases. We detected lung involvement in 3 cases, paranasal sinus involvement in 4 cases and vascular involvement in 1 case. Soft tissues were involved in 5 cases. Bone involvement was demonstrated in 3 patients. The most frequent radiologic finding was widespread infectious involvement of soft tissues, bones and neighboring structures such as bursae and tendons and respiratory system. PMID- 27265189 TI - A Case Report: Large Granular Cell Leukemia/Lymphoma (LGL). AB - We presented a 64-year-old male patient with T-large granular cell leukemia/lymphoma with an agressive clinical course. Large granular lymphocytes were noted on peripheral blood smear. The phenotyping of the cells was typical T cell lineage [CD2 (+), CD3 (+), CD5 (+)]. Clonal rearrangement of the T-cell receptor gene (TCR) was demonstrated by DNA hybridization technique. Large granular cell leukemia/lymphoma is a distinct entity with spesific clinicobiological aspects. The clinical spectrum is wide and immunophenotyping and genotyping studies need to make a diagnosis. PMID- 27265190 TI - Pulmonary Tuberculosis Associated with Autoimmune Hemolytic Anemia: An Unusual Presentatio. AB - Coombs' positive hemolytic anemia is exceedingly rare in tuberculosis. We herein report a patient with tuberculosis associated with Coombs' positive hemolytic anemia that was responded to antituberculosis therapy. She was admitted to the hospital because of recent-onset fatigue, weakness, nonproductive cough, pallor and scleral jaundice. Coombs positive hemolytic anemia and pulmoner tuberculosis was diagnosed. Following antituberculosis therapy, laboratory and clinical finding related to autoimmune hemolytic anemia disappeared. PMID- 27265191 TI - Plasmacytoma in the Bilateral Breast. PMID- 27265192 TI - Solitary Plasmacytoma of Tibia in a 29-Year-Old Woman. AB - Solitary plasmacytoma of the bone is a plasma cell tumor characterized by a single bone lesion with no evidence of myeloma elsewhere, including fewer than 5% plasma cells in the bone marrow. Although median age is about 14 years younger than that of patients with multiple myeloma, both diseases are extremely uncommon under 30 years of age. Solitary plasmacytoma of bone seem to have a prediction to occur in the axial skeleton, particularly in a vertebra and long bones are rarely affected. Herein, we report a case of solitary plasmacytoma of bone involving the tibia in a 29-year-old woman. PMID- 27265194 TI - Fletcher Factor Deficiency. PMID- 27265193 TI - Images in Haematology Edit by: Hamdi Akan. PMID- 27265195 TI - The Effect of ABO Incompatibility on Overall Survival of Patients Undergoing Allogeneic Bone Marrow Transplantation. PMID- 27265196 TI - Making the invisible visible: a microfluidic chip using a low refractive index polymer. AB - Microfluidic frameworks known as micro-total-analysis-systems or lab-on-a-chip have become versatile tools in cell biology research, since functional biochips are able to streamline dynamic observations of various cells. Glass or polymers are generally used as the substrate due to their high transparency, chemical stability and cost-effectiveness. However, these materials are not well suited for the microscopic observation of cell migration at the fluid boundary due to the refractive index mismatch between the medium and the biochip material. For this reason, we have developed a new method of fabricating three-dimensional (3D) microfluidic chips made of the low refractive index fluoric polymer CYTOP. This novel fabrication procedure involves the use of a femtosecond laser for direct writing, followed by wet etching with a dilute fluorinated solvent and annealing, to create high-quality 3D microfluidic chips inside a polymer substrate. A microfluidic chip made in this manner enabled us to more clearly observe the flagellum motion of a Dinoflagellate moving in circles near the fluid surface compared to the observations possible using conventional microfluidic chips. We believe that CYTOP microfluidic chips made using this new method may allow more detailed analysis of various cell migrations near solid boundaries. PMID- 27265197 TI - SEARCHBreast: An online resource designed to increase the efficiency of using materials derived from breast cancer studies in animals. PMID- 27265198 TI - Intense, stable and excitation wavelength-independent photoluminescence emission in the blue-violet region from phosphorene quantum dots. AB - Nanoscale phosphorene quantum dots (PQDs) with few-layer structures were fabricated by pulsed laser ablation of a bulk black phosphorus target in diethyl ether. An intense and stable photoluminescence (PL) emission of the PQDs in the blue-violet wavelength region is clearly observed for the first time, which is attributed to electronic transitions from the lowest unoccupied molecular orbital (LUMO) to the highest occupied molecular orbital (HOMO) and occupied molecular orbitals below the HOMO (H-1, H-2), respectively. Surprisingly, the PL emission peak positions of the PQDs are not red-shifted with progressively longer excitation wavelengths, which is in contrast to the cases of graphene and molybdenum disulphide quantum dots. This excitation wavelength-independence is derived from the saturated passivation on the periphery and surfaces of the PQDs by large numbers of electron-donating functional groups which cause the electron density on the PQDs to be dramatically increased and the band gap to be insensitive to the quantum size effect in the PQDs. This work suggests that PQDs with intense, stable and excitation wavelength-independent PL emission in the blue-violet region have a potential application as semiconductor-based blue violet light irradiation sources. PMID- 27265199 TI - Melatonin reversed tumor necrosis factor-alpha-inhibited osteogenesis of human mesenchymal stem cells by stabilizing SMAD1 protein. AB - Tumor necrosis factor-alpha (TNFalpha) plays a pivotal role in inflammation related osteoporosis through the promotion of bone resorption and suppression of bone formation. Numerous drugs have been produced to treat osteoporosis by inhibiting bone resorption, but they offer few benefits to bone formation, which is what is needed by patients with severe bone loss. Melatonin, which can exert both anti-inflammatory and pro-osteogenic effects, shows promise in overcoming TNFalpha-inhibited osteogenesis and deserves further research. This study demonstrated that melatonin rescued TNFalpha-inhibited osteogenesis of human mesenchymal stem cells and that the interactions between SMURF1 and SMAD1 mediated the crosstalk between melatonin signaling and TNFalpha signaling. Additionally, melatonin treatment was found to downregulate TNFalpha-induced SMURF1 expression and then decrease SMURF1-mediated ubiquitination and degradation of SMAD1 protein, leading to steady bone morphogenetic protein-SMAD1 signaling activity and restoration of TNFalpha-impaired osteogenesis. Thus, melatonin has prospects for treating osteoporosis caused by inflammatory factors due to its multifaceted functions on regulation of bone formation, bone resorption, and inflammation. Further studies will focus on unveiling the specific mechanisms by which melatonin downregulates SMURF1 expression and confirming the clinical therapeutic value of melatonin in the prevention and therapy of bone loss associated with inflammation. PMID- 27265200 TI - Intraamniotic inflammation and umbilical cord blood interleukin-6 concentrations in pregnancies complicated by preterm prelabor rupture of membranes. AB - OBJECTIVE: To evaluate umbilical cord blood interleukin (IL)-6 concentrations and the occurrence of fetal inflammatory response syndrome (FIRS) with respect to microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). METHODS: One-hundred-eighty-eight women with singleton pregnancies complicated by PPROM between gestational ages of 24 + 0 and 36 + 6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood IL-6 concentrations were evaluated using ELISA kits. FIRS was defined as umbilical cord blood IL-6 > 11 pg/mL. RESULT: Women with MIAC and IAI had higher IL-6 concentrations than women without these complications (with MIAC: median 18.1 pg/mL versus without MIAC: median 5.8; p < 0.0001; with IAI: median 32.9 pg/mL, versus without IAI: median 5.8; p < 0.0001). Women with IAI with MIAC and women with IAI without MIAC had the highest umbilical cord blood IL-6 concentrations (medians: 32.6 and 39.4 pg/mL) and rates of FIRS (78% and 67%). CONCLUSIONS: IAI was associated with the highest umbilical cord blood IL-6 concentrations and rate of FIRS independent of the presence or absence of MIAC. PMID- 27265201 TI - "It's Like a Disease": Women's perceptions of caesarean sections in Ghana's Upper West Region. AB - PROBLEM: While caesarean sections in developing contexts act as a marker for access to skilled care, little is known about the health outcomes of caesarean sections. With calls for a more in depth understanding of women's perceptions of this procedure in resource poor settings, this paper explores women's perceptions and experiences of caesarean birth in the context of Ghana's Maternal Exemption Policy of the National Health Insurance Scheme in the Upper West Region. METHODS: A qualitative study using 10 focus group discussions and 30 in depth interviews of mothers and pregnant women were conducted. The results were thematically analysed. FINDINGS: Drawing on theories of feminist geography and embodiment, the results suggest most women perceive caesarean section birth as highly problematic, acting as a long term disease, which hinders their ability to engage in economic activities and care for their children. In the context of the Maternal Exemption Policy, caesarean section birth restricts a woman's ability to secure further health insurance for themselves and newborn child, leaving long term access to health care uncertain. Findings also suggest long term repercussions of caesarean sections may go beyond the physical health of the mother and child to include other socio-cultural and contextual challenges. DISCUSSION: Accordingly, caesarean sections position women in a multifaceted situation of vulnerability. This underscores the need for context appropriate maternal health programmes in developing countries. PMID- 27265202 TI - Systemic saturated lysophosphatidylcholine is associated with hepatic function in patients with liver cirrhosis. AB - Serum lysophosphatidylcholine (LPC) is described to decline in patients with chronic liver diseases. Here it was evaluated which of the LPC species are associated with liver function. LPC species were quantified by direct flow injection electrospray ionization tandem mass spectrometry in serum of 45 patients with mainly alcoholic liver cirrhosis. Saturated LPC is 52.1 (31.7 110.0) MUmol/l in serum of patients with CHILD-PUGH score C (decompensated liver cirrhosis) and significantly lower compared to patients with well-compensated disease (CHILD-PUGH score A) with 114.1 (12.3-401.4) MUmol/l. Mono- and polyunsaturated LPC are not changed in these groups. Saturated LPC is negatively correlated with the model for end-stage liver disease score, bilirubin and galectin-3 and positively with Quick prothrombin time. Ascites and varices are complications of liver cirrhosis. Saturated LPC does, however, not correlate with hepatic venous pressure gradient, ascites volume and variceal size. Unexpectedly, saturated LPC measured in serum of 42 patients declines from 88.4 (27.8-177.5) MUmol/l to 72.4 (27.6-141.8) MUmol/l shortly after transjugular intrahepatic portosystemic shunt implantation. Hepatic vein saturated LPC (82.3 (12.4-161.7) MUmol/l) is higher than portal vein levels (78.8 (10.1-161.0) MUmol/l) suggesting hepatic release of this lipid species. Current data demonstrate that systemic saturated LPC species are reduced in patients with decompensated liver cirrhosis and associated with mortality risk. PMID- 27265204 TI - Intra-uterine undernutrition amplifies age-associated glucose intolerance in pigs via altered DNA methylation at muscle GLUT4 promoter. AB - The present study aimed to investigate the effect of maternal malnutrition on offspring glucose tolerance and the epigenetic mechanisms involved. In total, twelve primiparous Landrace*Yorkshire gilts were fed rations providing either 100 % (control (CON)) or 75 % (undernutrition (UN)) nutritional requirements according to the National Research Council recommendations, throughout gestation. Muscle samples of offspring were collected at birth (dpn1), weaning (dpn28) and adulthood (dpn189). Compared with CON pigs, UN pigs showed lower serum glucose concentrations at birth, but showed higher serum glucose and insulin concentrations as well as increased area under the blood glucose curve during intravenous glucose tolerance test at dpn189 (P<0.05). Compared with CON pigs, GLUT-4 gene and protein expressions were decreased at dpn1 and dpn189 in the muscle of UN pigs, which was accompanied by increased methylation at the GLUT4 promoter (P<0.05). These alterations in methylation concurred with increased mRNA levels of DNA methyltransferase (DNMT) 1 at dpn1 and dpn28, DNMT3a at dpn189 and DNMT3b at dpn1 in UN pigs compared with CON pigs (P<0.05). Interestingly, although the average methylation levels at the muscle GLUT4 promoter were decreased at dpn189 compared with dpn1 in pigs exposed to a poor maternal diet (P<0.05), the methylation differences in individual CpG sites were more pronounced with age. Our results indicate that in utero undernutrition persists to silence muscle GLUT4 likely through DNA methylation during the ageing process, which may lead to the amplification of age-associated glucose intolerance. PMID- 27265205 TI - Hydrogen Treatment for Superparamagnetic VO2 Nanowires with Large Room Temperature Magnetoresistance. AB - One-dimensional (1D) transition metal oxide (TMO) nanostructures are actively pursued in spintronic devices owing to their nontrivial d electron magnetism and confined electron transport pathways. However, for TMOs, the realization of 1D structures with long-range magnetic order to achieve a sensitive magnetoelectric response near room temperature has been a longstanding challenge. Herein, we exploit a chemical hydric effect to regulate the spin structure of 1D V-V atomic chains in monoclinic VO2 nanowires. Hydrogen treatment introduced V(3+) (3d(2) ) ions into the 1D zigzag V-V chains, triggering the formation of ferromagnetically coupled V(3+) -V(4+) dimers to produce 1D superparamagnetic chains and achieve large room-temperature negative magnetoresistance (-23.9 %, 300 K, 0.5 T). This approach offers new opportunities to regulate the spin structure of 1D nanostructures to control the intrinsic magnetoelectric properties of spintronic materials. PMID- 27265206 TI - Involvement of glucagon-like peptide-1 in the glucose-lowering effect of metformin. AB - Metformin is an oral antihyperglycaemic drug used in the first-line treatment of type 2 diabetes. Metformin's classic and most well-known blood glucose-lowering mechanisms include reduction of hepatic gluconeogenesis and increased peripheral insulin sensitivity. Interestingly, intravenously administered metformin is ineffective and recently, metformin was shown to increase plasma concentrations of the glucose-lowering gut incretin hormone glucagon-like peptide-1 (GLP-1), which may contribute to metformin's glucose-lowering effect in patients with type 2 diabetes. The mechanisms behind metformin-induced increments in GLP-1 levels remain unknown, but it has been hypothesized that metformin stimulates GLP-1 secretion directly and/or indirectly and that metformin prolongs the half-life of GLP-1. Also, it has been suggested that metformin may potentiate the glucose lowering effects of GLP-1 by increasing target tissue sensitivity to GLP-1. The present article critically reviews the possible mechanisms by which metformin may affect GLP-1 levels and sensitivity and discusses whether such alterations may constitute important and clinically relevant glucose-lowering actions of metformin. PMID- 27265207 TI - A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect. AB - Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species. PMID- 27265208 TI - Ultrastructural observation of oocytes in six types of stony corals. AB - In this study, the ultrastructure of the oocytes of 6 types of scleractinian corals was observed by transmission electron microscopy (TEM). Moreover, histological and ultrastructural analyses were performed to improve our understanding of the organelles involved in coral oocyte formation. In all 6 stony coral species, the microvilli were tubular and directly grew from the surface of the oocyte membrane; yolk bodies, lipid granules, and cortical alveoli accounted for most of the volume inside the oocytes, suggesting that they are associated with energy storage and buoyancy. Clear differences were observed in the size of yolk bodies and lipid granules in the oocytes of the 6 stony coral species, which occupied approximately 55%-80% of the inner space of the oocytes. Galaxea fascicularis exhibited the largest lipid granule volume, but the oocytes contained only an average number of 12.45 lipid granules per unit area. Only Montipora incrassata oocytes contained symbiotic algae. The smallest size and proportion of lipid granules in M. incrassata oocytes may be attributed to the presence of symbiotic algae and large yolk bodies, which may help oocytes produce energy and function as a nutritional source. This study is crucial for improving the understanding of the basic biology of coral reproduction, and the ensuing datasets is critical for conservation-oriented studies seeking to cryopreserve corals during these times of dramatic global climate change. PMID- 27265209 TI - Triggering through NOD-2 Differentiates Bone Marrow Precursors to Dendritic Cells with Potent Bactericidal activity. AB - Dendritic cells (DCs) play a crucial role in bridging innate and adaptive immunity by activating naive T cells. The role of pattern recognition receptors like Toll-Like Receptors and Nod-Like Receptors expressed on DCs is well-defined in the recognition of the pathogens. However, nothing is precisely studied regarding the impact of NOD-2 signaling during the differentiation of DCs. Consequently, we explored the role of NOD-2 signaling in the differentiation of DCs and therefore their capability to activate innate and adaptive immunity. Intriguingly, we observed that NOD-2 stimulated DCs (nDCs) acquired highly activated and matured phenotype and exhibited substantially greater bactericidal activity by robust production of nitric oxide. The mechanism involved in improving the functionality of nDCs was dependent on IFN-alphabeta signaling, leading to the activation of STAT pathways. Furthermore, we also observed that STAT-1 and STAT-4 dependent maturation and activation of DCs was under the feedback mechanism of SOCS-1 and SOCS-3 proteins. nDCs acquired enhanced potential to activate chiefly Th1 and Th17 immunity. Taken together, these results suggest that nDCs can be exploited as an immunotherapeutic agent in bolstering host immunity and imparting protection against the pathogens. PMID- 27265211 TI - Ataxia telangiectasia: a syndrome deserving attention and study. PMID- 27265210 TI - Surgical Resident Radiation Knowledge, Attitudes, Practices, and Exposures. AB - OBJECTIVE: To investigate the level of ionizing radiation exposure among surgical residents and to evaluate resident knowledge, attitudes, and practices regarding exposures. DESIGN: An observational study was conducted using radiation exposure data for surgical residents who wore film badge dosimeters. A cross-sectional survey was electronically administered at the end of the year, examining resident knowledge, attitudes, and practices concerning radiation exposures. SETTING: Community teaching hospital in the Midwest. PARTICIPANTS: Surgical residents who wore a badge for the full calendar year and completed study survey. Excluded were graduating chiefs and interns who only had 6 calendar months of data. RESULTS: A total of 14 surgical residents (100%) were engaged in 168 rotations during study year. Primarily-general surgery (n = 103, 61%), night float (n = 16, 10%), trauma (n = 15, 9%), and vascular (n = 13, 8%). Radiation exposures were greater than a null value during most rotations (i.e., general surgery and night float), with no exposure above occupational thresholds. Certain rotations, namely vascular and trauma, had episodic high exposures. When asked if protective efforts changed during higher-risk rotations, responses revealed they increased (64%) or did not change (36%). A low Cronbach alpha (alpha = 0.2634) demonstrated that precaution use was not universal and had varied rationale. Percentage of correct radiation knowledge questions was 62%. A multilevel model predicting exposure had a significant multiplicative cross-level interaction term (p < 0.0001) between resident-level exposure and rotation type. CONCLUSIONS: Radiation exposure levels for surgical residents have not been previously investigated. Data demonstrated that surgical residents were not at a greater risk than other medical personnel. However, the study demonstrated detectable radiation exposures that were statistically greater than a null value for the most common rotations. Stochastic and dose-response effects of radiation make any exposure a concern. Attempts to lessen exposures are worthwhile, with study results identifying a need for greater safety precaution education and adherence. PMID- 27265219 TI - A new helvolic acid derivative from an endophytic Fusarium sp. of Ficus carica. AB - A new helvolic acid derivative named helvolic acid methyl ester (1), together with two known helvolic acid compounds, helvolic acid (2) and hydrohelvolic acid (3), were isolated from the fermentation of endophytic fungus Fusarium sp. in Ficus carica leaves. Their structures were elucidated and identified by spectroscopic methods. Compounds 1-3 showed potent antifungal and antibacterial activities. PMID- 27265220 TI - Outcome of Gleason 3 + 5 = 8 Prostate Cancer Diagnosed on Needle Biopsy: Prognostic Comparison with Gleason 4 + 4 = 8. AB - PURPOSE: ISUP (International Society for Urologic Pathology) and WHO adopted prognostic Grade Groups 1 to 5 that simplify prostate cancer grading for prognosis. Grade Group 4 is Gleason score 8 cancer, which is heterogeneous, and it encompasses Gleason score 4 + 4 = 8, 3 + 5 = 8 and 5 + 3 = 8. The comparative prognostic implications of these various Gleason scores had not been studied by urological pathologists after a re-review of slides. MATERIALS AND METHODS: Patients with a highest biopsy Gleason score of 3 + 5 = 8 or 4 + 4 = 8 were included in the study. Controls were cases with a highest Gleason score of 4 + 3 = 7 or 9-10. A total of 423 prostatic biopsy cases accessioned from 2005 to 2013 at 2 institutions were reviewed. Clinicopathological findings and followup (median 33.4 months) were assessed. RESULTS: Among Gleason score 8 cancers the cancer status outcome in 51 men with Gleason score 3 + 5 = 8 was marginally worse than in 114 with Gleason score 4 + 4 = 8 (p = 0.04). This was driven by a persistent nonmetastatic (after radiation/hormone therapy) cancer rate of 37% among Gleason score 3 + 5 = 8 cases vs 24% among Gleason score 4 + 4 = 8 cases. Conversely, cancer specific survival at 36-month followup was 97.8% in 3 + 5 cases vs 92.6% in 4 + 4 cases but this was not significant (p = 0.089). Cancer specific survival in the Gleason score 8 group was dichotomized by the presence of cribriform growth (p = 0.018). All Gleason score categories did not differ in the fraction of biopsy cores positive, clinical presentation or pathological findings, including the frequency of Gleason pattern 5, in 70 patients who underwent prostatectomy. CONCLUSIONS: Using the most current standards of prostate cancer grading the prognosis is not different in Gleason score 3 + 5 = 8 and 4 + 4 = 8 cancers. This justifies including both in Grade Group 4. PMID- 27265221 TI - Histological and Urodynamic Effects of Autologous Stromal Vascular Fraction Extracted from Fat Tissue with Minimal Ex Vivo Manipulation in a Porcine Model of Intrinsic Sphincter Deficiency. AB - PURPOSE: To evaluate the healing abilities of autologous stem cell therapy (stromal vascular fraction) prepared from adipose tissue we used an automated system without an ex vivo culture phase in a pig model of intrinsic sphincteric deficiency. MATERIALS AND METHODS: A total of 15 pigs underwent endoscopic section of the urethral sphincter. Animals were then randomly assigned to 3 groups, including 1) controls without stromal vascular fraction injection, 2) early injection with stromal vascular fraction 2 to 3 days after section and 3) late stromal vascular fraction injection delivery 30 days after injury. Extraction and stromal vascular fraction injection were performed as a single procedure. The stromal vascular fraction was characterized by flow cytometry. Mesenchymal stem cell-like cells were enumerated by clonogenicity (cfu fibroblast) assay. Study end points included histological assessment of the urethral injury surface and urodynamics to determine maximum urethral pressure. RESULTS: Flow cytometry analysis revealed a mesenchymal stem cell-like phenotype in a mean +/- SD of 47.3% +/- 11.8% of stromal vascular fraction cells. The cfu fibroblast frequency was 1.3 to 6.6/100 stromal vascular fraction cells (1.3% to 6.6%). Stromal vascular fraction injection was associated with a reduction of the urethral injury surface in the early and late injection groups compared with the respective controls (7% vs 17% and 1% vs 13%, p = 0.050 and 0.029, respectively). On day 30 after injection maximum urethral pressure was significantly higher in the injected groups than in the control group, that is 64% vs 50% of maximum urethral pressure on day 0 (p = 0.04). CONCLUSIONS: These data demonstrate the ability of an autologous stromal vascular fraction to improve the urethral healing process in a large animal model of intrinsic sphincteric deficiency. PMID- 27265223 TI - Thrombosis in the antiphospholipid syndrome. PMID- 27265222 TI - Thoracic stent graft versus surgery for thoracic aneurysm. AB - BACKGROUND: Thoracic aortic aneurysm (TAA) is an uncommon disease with an incidence of 10.4 per 100,000 inhabitants. It occurs mainly in older individuals and is evenly distributed among both sexes. There are no signs or symptoms indicative of the presence of the disease. Progressive but unpredictable enlargement of the dilated aorta is the natural course of the disease and can lead to rupture. Open chest surgical repair using prosthetic graft interposition has been a conventional treatment for TAAs. Despite improvements in surgical procedures perioperative complications remain significant. The alternative option of thoracic endovascular aneurysm repair (TEVAR) is considered a less invasive and potentially safer technique, with lower morbidity and mortality compared with conventional treatment. Evidence is needed to support the use of TEVAR for these patients, rather than open surgery. This is an update of the review first published in 2009. OBJECTIVES: This review aimed to assess the efficacy of TEVAR versus conventional open surgery in patients with thoracic aortic aneurysms. SEARCH METHODS: For this update the Cochrane Vascular Information Specialist searched the Specialised Register (last searched January 2016) and CENTRAL (2015, Issue 12). SELECTION CRITERIA: Randomised controlled trials in which patients with TAAs were randomly assigned to TEVAR or open surgical repair. DATA COLLECTION AND ANALYSIS: Two review authors independently identified and evaluated potential trials for eligibility. Excluded studies were further checked by another author. We did not perform any statistical analyses as no randomised controlled trials were identified. MAIN RESULTS: We did not find any published or unpublished randomised controlled trials comparing TEVAR with conventional open surgical repair for the treatment of thoracic aortic aneurysms. AUTHORS' CONCLUSIONS: Stent grafting of the thoracic aorta is technically feasible and non randomised studies suggest reduction of early outcomes such as paraplegia, mortality and hospital stay. High quality randomised controlled trials assessing all clinically relevant outcomes including open-conversion, aneurysm exclusion, endoleaks, and late mortality are needed. PMID- 27265224 TI - Antioxidant effect of vitamin E in the treatment of nutritional iron deficiency anemia. AB - Oxidant status and antioxidants play important roles in anemias. The present study was conducted to investigate the oxidant-antioxidant status in iron deficiency anemia (IDA), and to evaluate the antioxidant effect of vitamin E in IDA treatment. Ten patients with IDA aged nine months were given only iron treatment, whereas another 10 patients were administered both iron and vitamin E. The complete blood count, plasma malonyldialdehyde (MDA) level, erythrocyte superoxide dismutase level, and the serum vitamin E level, both before and within the treatment phases were examined. The reticulocyte count at the first week of treatment was found lower in the vitamin E-treated group. The mean corpuscular volume (MCV) was found higher in the vitamin E-treated group at the end of therapy. The malonyldialdehyde levels of the group treated with vitamin E were found lower during treatment. These results suggest that iron administration in IDA treatment may stimulate lipid peroxidation, and that vitamin E supplied with iron may reduce the MDA production. The hematological indications of the findings of our study are that the reticulocyte response develops earlier and the microcytosis recovery occurs more rapidly in the vitamin E-administered group in comparison with the group treated with iron only. PMID- 27265225 TI - Inhibitor screening for patients with hemophilia in Turkey. AB - Development of factor VIII inhibitors remains the most serious and life threatening complication of hemophilia therapy. The aim of this study was to determine the prevalence of inhibitor development in Turkish patients with hemophilia. Totally 1226 patients were screened [HA: 1057, HB: 105, von Willebrand's disease (vWD): 64]. Ages ranged from 1 to 55 years (mean: 16.5 years). Sixty-two percent of patients (657/1057) were severe hemophilia. This study showed that inhibitor prevalence in Turkish hemophiliacs exposed to factor concentrates and fresh frozen plasma (FFP) is 11.2% for all HA and 15.8% for severe HA versus 1.9% for HB after eliminating transient inhibitors. Totally 122 patients were found inhibitor positive [high responder (HR) inhibitor= 60 and low responder (LR) inhibitor= 59 for HA/2 LR for HB/1 LR for vWD]. Thanks to this project, patients with inhibitor development can be treated with specific products such as recombinant factor VIIa or activated protrombin complex concentrates for their bleeding episodes or in their elective operations. PMID- 27265226 TI - Intron 1 inversion mutation among Turkish hemophilia A patients. AB - Hemophilia A is an X-linked bleeding disorder resulting mostly from heterogeneous point mutations in the factor VIII (F8) gene. Small/large gene deletions, insertions and gross gene rearrangements underlie the molecular pathogenesis of the disease. Two large inversion mutations due to intrachromosomal recombinations between inverted repeats found in intronic sequences and upstream regions of the F8 gene result in severe hemophilia A. The intron 1 inversion mutation is responsible for about 2% of the cases in various populations. Herein, we report the establishment of the long polymerase chain reaction (PCR) intron 1 inversion mutation detection in our laboratory and a similar frequency of 1-2% among Turkish patients. PMID- 27265227 TI - Effect of pentoxifylline and indomethacin on rabbits with endotoxin induced disseminated intravascular coagulation (DIC) and comparison with heparin. AB - We evaluated the effects of pentoxifylline and indomethacin and heparin in a rabbit model of disseminated intravascular coagulation (DIC) induced by infusion of 100 MUg/kg/hour of Escherichia coli endotoxin lipoplysaccharide (LPS) for 6 hour. Heparin, indomethacin, pentoxifylline or saline were administered simultaneously with LPS. In addition, a control group was formed which was administered only saline. Hemostatic markers at 0, 1/2, 2, and 6 hour as well as histopathologic changes in the organs and the mortality at 24 hour were determined. The infusion of LPS caused a severe impairment in hemostasis and fibrin accumulation in the pulmonary vasculature. Heparin significantly improved hemostatic impairment and reduced the fibrin accumulation in the pulmonary vasculature. Pentoxifylline and indomethacin had no significant effect on DIC, except that pentoxifylline prevented the decrement in platelet count slightly (p< 0.05). None of the drugs, including heparin, had any effect on mortality. As a result, the prevention of the synthesis of only one cytokine or autocoid is not considered enough to control the results of endotoxemia. PMID- 27265228 TI - Serum transforming growth factor beta 1 levels in multiple myeloma patients. AB - Cytokinesis plays an important role in the etiology of multiple myeloma. The transforming growth factor (TGF) beta 1 levels in 82 sera from 60 patients with multiple myeloma were analyzed by ELISA. Fourty one sample were obtained before treatment from newly diagnosed patients, 22 after treatment from the same patients and 19 from relapsed/refractory patients. Serum median TGF level of newly diagnosed patients was 769.5 ng/mL (126-1853), and the relapsed/refractory patients had similar levels. TGF levels after chemotherapy were not different between patients that reached plateau phase and those who remained refractory. We found a negative correlation between TGF and C-reactive protein and blood urea nitrogen and a positive correlation between TGF and hemoglobin level in newly diagnosed patients. After treatment, it was determined that TGF levels at diagnosis were higher in patients who reached plateau phase than in the refractory patients. Elevated serum TGF concentration at diagnosis in multiple myeloma patients may be a favorable predictor of response. PMID- 27265229 TI - Hemophilic pseudotumor-is there a role of radiotherapy? A case report with review of literature. AB - Hemophilic pseudotumors are a rare but serious complication. They are more common in the weight-bearing joints. These lesions could be treated by conservative measures using factor VIII cryoprecipitate or by radiation therapy as an alternative to surgery with good results. We present a case of chronic hemophilia with pseudotumor of the right knee joint who was treated with low dose external beam radiation with fair results. PMID- 27265230 TI - Drug-induced thrombocytopenia during G-CSF therapy in a patient with chronic neutropenia. AB - A one-year-old infant presented with recurrent perianal abscesses and pneumonia, and was diagnosed with chronic neutropenia. Treatment with granulocyte colony stimulating factor (G-CSF) was initiated, and thrombocytopenia was detected three weeks later. The drug was discontinued but the patient's platelet count did not improve. A short course of high-dose methylprednisolone was administered, and both the platelet and neutrophil counts returned to normal. Based on this response, in order to maintain the neutrophil count the steroid treatment was continued for one year with tapered doses. At the time of writing, the patient had been doing well for 13 months without treatment. This report highlights that G-CSF treatment for severe chronic neutropenia in a child may be associated with thrombocytopenia. PMID- 27265231 TI - Foot-drop due to involvement of lumbosacral plexus in diffuse large B-cell lymphoma. AB - Extranodal nerve system involvement is seen in approximately 5% of the patients with non-Hodgkin's lymphomas. It causes as primary or secondary infiltration of brain, leptomeninges, or peripheral nerves and the signs of spinal cord compression. Here we present a 67-year-old woman with advanced stage diffuse large B-cell lymphoma who developed foot-drop due to lumbosacral plexus involvement. PMID- 27265232 TI - Images in Hematology. PMID- 27265233 TI - Recent advances, eosinophils, eosinophilia and hypereosinophilic syndrome. PMID- 27265234 TI - A unique SaeS allele overrides cell-density dependent expression of saeR and lukSF-PV in the ST30-SCCmecIV lineage of CA-MRSA. AB - ST30 (CC30)-SCCmec IV (USA1100) is one of the most common community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) lineages. ST30 isolates typically carry lukSF-PV genes encoding the Panton-Valentine leukocidin (PVL) and are responsible for outbreaks of invasive infections worldwide. In this study, twenty CC30 isolates were analyzed. All were very susceptible to non-beta-lactam antimicrobials, 18/20 harbored the lukSF-PV genes, only 1/20 exhibited agr-rnaIII dysfunction, and the majority was not able to form biofilm on inert surfaces. Analysis of lukSF-PV temporal regulation revealed that opposite to other CA-MRSA isolates, these genes were more highly expressed in early log phase than in stationary phase. This inverted lukSF-PV temporal expression was associated with a similar pattern of saeRS expression in the ST30 isolates, namely high level expression in log phase and reduced expression in stationary phase. Reduced saeRS expression in stationary phase was associated with low expression levels of the sae regulators, agr and agr-upregulator sarA, which activate the stationary phase sae-P1 promoter and overexpression of agr-RNAIII restored the levels of saeR and lukSF-PV trancripts in stationary phase. Altered SaeRS activity in the ST30 isolates was attributed to amino acid substitutions (N227S, E268K and S351T) in the HTPase_c domain of SaeS (termed SaeS(SKT)). Complementation of a USA300 saeS mutant with the saeS(SKT) and saeS alleles under the direction of the log phase sae-P3 promoter revealed that saeR and lukSF-PV transcription levels were more significantly activated by saeS(SKT) than saeS. In summary our data identify a unique saeS allele (saeS(SKT)) which appears to override cell-density dependent SaeR and PVL expression in ST30 CA-MRSA isolates. Further studies to determine the contribution of saeS(SKT) allele to the pathogenesis of infections caused by ST30 isolates are merited. PMID- 27265235 TI - Elevated expression of IL-9 correlates with disease course of recurrent tuberculosis. PMID- 27265236 TI - The prevalence, population structure and screening test specificity of penicillin susceptible Staphylococcus aureus bacteremia isolates in Malmo, Sweden. AB - OBJECTIVES: The objectives of this study were to examine the prevalence of penicillin-susceptible bacteremic Staphylococcus aureus in the Malmo area in 2014, to re-evaluate the phenotypic methods of penicillinase detection on these isolates, and to investigate the clonal distribution of penicillin-susceptible isolates. METHODS: All non-redundant S. aureus from blood in the Malmo catchment area in southern Sweden 2014 were screened for penicillin susceptibility using PcG 1U disk diffusion, E-test PcG and the nitrocefin test. All isolates screened as likely susceptible were subjected to PCR for detection of penicillinase (blaZ) and spa-typing. RESULTS: Almost one out of three bacteremic isolates (80/257; 31.1%) were susceptible to penicillin. All screening methods except for the nitrocefin test alone had a low proportion of isolates falsely tested as susceptible, but no method used in the study had perfect specificity compared with PCR. Penicillin-susceptible isolates had a distinct phylogenetic distribution, and two clonal complexes (CC5 and CC45) constituted half of the isolates. CONCLUSION: Almost one third of S. aureus isolated from blood in southern Sweden in 2014 was susceptible to penicillin. Considering that intravenous penicillin has theoretical advantages compared with the standard treatment in the study area, we argue that routine testing of penicillin susceptibility should be reconsidered. PMID- 27265237 TI - Carbazole Annulation via Cascade Nucleophilic Addition-Cyclization Involving 2 (Silyloxy)pentadienyl Cation. AB - We report a new strategy toward the synthesis of highly functionalized carbazoles via 2-(silyloxy)pentadienyl cation intermediates, which were generated upon ionization of vinyl-substituted alpha-hydroxy silyl enol ethers under Bronsted acid catalysis. These electrophilic species were found to readily undergo cascade reactions with substituted indoles to generate carbazole molecular scaffolds in good yields via a sequence of regioselective nucleophilic addition, followed by intramolecular dehydrative cyclization. PMID- 27265238 TI - Dorsal Arthroscopic Approach and Intra-Articular Anatomy of the Bovine Antebrachiocarpal and Middle Carpal Joints. AB - OBJECTIVE: To determine arthroscopic approaches to the dorsal synovial compartments of the antebrachiocarpal and middle carpal joints in adult cattle, and to describe the arthroscopic intra-articular anatomy from each approach. STUDY DESIGN: Ex vivo study. ANIMALS: Six fresh adult bovine cadavers. METHODS: Two carpi were injected with latex and dissected to determine the ideal location for arthroscopic portals. Arthroscopy of the antebrachiocarpal and middle carpal joints of 10 carpi was then performed. The dorsolateral approach was made between the extensor carpi radialis and common digital extensor tendons. The dorsomedial approach was made medial to the extensor carpi radialis tendon, midway between the distal radius and proximal row of carpal bones (antebrachiocarpal joint) and midway between the two rows of carpal bones (middle carpal joint), with the joint in flexion. RESULTS: Arthroscopy of the antebrachiocarpal joint allowed visualization of the distal radius, proximal aspect of the radial, intermediate and ulnar carpal bones, and a palmar ligament located between the radius and the intermediate carpal bone. The approach to the middle carpal joint allowed visualization of the distal aspect of the radial, intermediate, and ulnar carpal bones, the proximal aspect of the fourth and fused second and third carpal bones and an interosseous ligament. The most lateral articular structures (lateral glenoid cavity of the distal radius, ulnar carpal and fourth carpal bones) were difficult to assess. CONCLUSION: Dorsal approaches to the antebrachiocarpal and middle carpal joints allowed visualization of most intra-articular dorsal structures in adult cattle. PMID- 27265239 TI - Water oxidation catalyzed by molecular di- and nonanuclear Fe complexes: importance of a proper ligand framework. AB - The synthesis of two molecular iron complexes, a dinuclear iron(iii,iii) complex and a nonanuclear iron complex, based on the dinucleating ligand 2,2'-(2-hydroxy 5-methyl-1,3-phenylene)bis(1H-benzo[d]imidazole-4-carboxylic acid) is described. The two iron complexes were found to drive the oxidation of water by the one electron oxidant [Ru(bpy)3](3+). PMID- 27265240 TI - The stabilizing effect of shear thinning on the onset of purely elastic instabilities in serpentine microflows. AB - We determine both experimentally and numerically the onset of elastic flow instabilities in viscoelastic polymer solutions with different levels of shear thinning. Previous experiments realized in microfluidic serpentine channels using dilute polymeric solutions showed that the onset of elastic instabilities strongly depends on the channel curvature. The scaling dependence is well captured by the general instability scaling criterion proposed by Pakdel and McKinley [Phys. Rev. Lett., 1996, 76, 2459:1-4]. We determine here the influence of fluid shear thinning on the onset of such purely-elastic flow instabilities. By testing a set of polyethylene oxide solutions of high molecular weight at different polymer concentrations in microfluidic serpentine channels we observe that shear thinning has a stabilizing effect on the microfluidic flow. Three dimensional numerical simulations performed using the White-Metzner model predict similar trends, which are not captured by a simple scaling analysis using the Pakdel-McKinley criterion. PMID- 27265241 TI - Improving Access to Liver Care Across the Continuum of Care: Opportunities and Challenges. PMID- 27265243 TI - Octahedral ruthenium complexes selectively stabilize G-quadruplexes. AB - A series of octahedral Ru(ii) complexes with an x-y planar tetradentate and two trans-z-axis ammonia ligands were synthesized. High stabilization of G quadruplexes was achieved upon pi-stacking with aromatic planar ligands. Unique interaction from z-axis ligands bestowed both excellent binding resistance to duplex DNA and selectivity towards the antiparallel topology. PMID- 27265242 TI - Effects of propolis and gamma-cyclodextrin on intestinal neoplasia in normal weight and obese mice. AB - Obesity is associated with colorectal cancer (CRC). This effect might be attributed to adipokine-supported signaling. We have established that propolis suppresses survival signaling in CRC cells in vitro; therefore, we ascertained the ability of a propolis supplement to modulate intestinal neoplastic development in C57BL/6J-ApcMin/+/J mice in the lean and obese state. To induce obesity, mice were fed with a Western diet containing 40% fat. Since the propolis supplement includes gamma-cyclodextrin, the interventions included diets supplemented with or without gamma-cyclodextrin. The animals were administered the following diets: (1) control diet, (2) control diet/gamma-cyclodextrin, (3) control diet/propolis, (4) Western diet, (5) Western diet/gamma-cyclodextrin, and (6) Western diet/propolis. Western diet, resulting in obesity, accelerated neoplastic progression, as evidenced by the larger size and higher grade dysplasia of the neoplasms. In the context of normal weight, gamma-cyclodextrin and propolis affected neoplastic progression, as determined by the size of the lesions and their grade of dysplasia. A statistically significant decrease in the number of adenomas was detected in mice fed a control diet with the propolis supplement (61.8 +/- 10.6 vs. 35.3 +/- 7.6, P = 0.008). Although there was no significant difference in the polyp numbers between the six groups, the mice with the lowest number and size of adenomas were those fed a Western diet with gamma cyclodextrin. This unexpected outcome might be explained by the increased levels of apoptosis detected in the intestinal tissues of these obese mice. We posit that butyrate derived from the metabolism of gamma-cyclodextrin may contribute to the decreased neoplastic burden in the context of obesity; however, future studies are required to address this possibility. PMID- 27265244 TI - Advances toward industrialization of novel molten salt electrochemical processes. AB - We have invented various novel molten salt electrochemical processes, that can be put to practical use in the fields of energy and materials. These processes are promising from both technological and commercial viewpoints, and they are currently under development for industrial application. To showcase current developments in work toward industrialization, we focus here on three of these processes: (1) electrolytic synthesis of ammonia from water and nitrogen under atmospheric pressure, (2) electrochemical formation of carbon film, and (3) plasma-induced discharge electrolysis to produce nanoparticles. PMID- 27265245 TI - Mechanistic investigations of CO-photoextrusion and oxidative addition reactions of early transition-metal carbonyls: (eta(5)-C5H5)M(CO)4 (M = V, Nb, Ta). AB - The mechanisms for the photochemical Si-H bond activation reaction are studied theoretically using a model system of the group 5 organometallic compounds, eta(5)-CpM(CO)4 (M = V, Nb, and Ta), with the M06-2X method and the Def2-SVPD basis set. Three types of reaction pathways that lead to final insertion products are identified. The structures of the intersystem crossings, which play a central role in these photo-activation reactions, are determined. The intermediates and transitional structures in either the singlet or triplet states are also calculated to provide a mechanistic explanation of the reaction pathways. All of the potential energy surfaces for the group 5 eta(5)-CpM(CO)4 complexes are quite similar. In particular, the theoretical evidence suggests that after irradiation using light, eta(5)-CpM(CO)4 quickly loses one CO ligand to yield two tricarbonyls, in either the singlet or the triplet states. The triplet tricarbonyl 16-electron intermediates, ([eta(5)-CpM(CO)3](3)), play a key role in the formation of the final oxidative addition product, eta(5)-CpM(CO)3(H)(SiMe3). However, the singlet counterparts, ([eta(5)-CpM(CO)3](1)), play no role in the formation of the final product molecule, but their singlet metal centers interact weakly with solvent molecules ((Me3)SiH) to produce alkyl-solvated organometallic complexes, which are observable experimentally. This theoretical evidence is in accordance with the available experimental observations. PMID- 27265246 TI - The role of the NADPH oxidase derived brain oxidative stress in the cocaine related death associated with excited delirium: A literature review. AB - Excited delirium syndrome (ExDS) is a term used to describe a clinical condition characterized by bizarre and aggressive behaviour, commonly associated with the use of psychoactive compounds, especially cocaine. The pathophysiology of ExDS is complex and not yet fully understood. In addition to a central dopamine hypothesis, other mechanisms are thought to be involved in cocaine-related ExDS, such as increased reactive oxygen species production by the family of the NADPH oxidase NOX enzymes. In this review, we will summarize current knowledge on the crucial contribution of brain NADPH oxidase derived oxidative stress in the development of cocaine-induced ExDS. Data from animal models as well as human evidence will be discussed. PMID- 27265247 TI - Substituent Effects on the [N-I-N](+) Halogen Bond. AB - We have investigated the influence of electron density on the three-center [N-I N](+) halogen bond. A series of [bis(pyridine)iodine](+) and [1,2-bis((pyridine-2 ylethynyl)benzene)iodine](+) BF4(-) complexes substituted with electron withdrawing and donating functionalities in the para-position of their pyridine nitrogen were synthesized and studied by spectroscopic and computational methods. The systematic change of electron density of the pyridine nitrogens upon alteration of the para-substituent (NO2, CF3, H, F, Me, OMe, NMe2) was confirmed by (15)N NMR and by computation of the natural atomic population and the pi electron population of the nitrogen atoms. Formation of the [N-I-N](+) halogen bond resulted in >100 ppm (15)N NMR coordination shifts. Substituent effects on the (15)N NMR chemical shift are governed by the pi population rather than the total electron population at the nitrogens. Isotopic perturbation of equilibrium NMR studies along with computation on the DFT level indicate that all studied systems possess static, symmetric [N-I-N](+) halogen bonds, independent of their electron density. This was further confirmed by single crystal X-ray diffraction data of 4-substituted [bis(pyridine)iodine](+) complexes. An increased electron density of the halogen bond acceptor stabilizes the [N...I...N](+) bond, whereas electron deficiency reduces the stability of the complexes, as demonstrated by UV kinetics and computation. In contrast, the N-I bond length is virtually unaffected by changes of the electron density. The understanding of electronic effects on the [N-X-N](+) halogen bond is expected to provide a useful handle for the modulation of the reactivity of [bis(pyridine)halogen](+)-type synthetic reagents. PMID- 27265248 TI - Taxonomic and ecological relevance of the chlorophyll a fluorescence signature of tree species in mixed European forests. AB - The variability of chlorophyll a fluorescence (ChlF) parameters of forest tree species was investigated in 209 stands belonging to six European forests, from Mediterranean to boreal regions. The modifying role of environmental factors, forest structure and tree diversity (species richness and composition) on ChlF signature was analysed. At the European level, conifers showed higher potential performance than broadleaf species. Forests in central Europe performed better than those in Mediterranean and boreal regions. At the site level, homogeneous clusters of tree species were identified by means of a principal component analysis (PCA) of ChlF parameters. The discrimination of the clusters of species was influenced by their taxonomic position and ecological characteristics. The species richness influenced the tree ChlF properties in different ways depending on tree species and site. Tree species and site also affected the relationships between ChlF parameters and other plant functional traits (specific leaf area, leaf nitrogen content, light-saturated photosynthesis, wood density, leaf carbon isotope composition). The assessment of the photosynthetic properties of tree species, by means of ChlF parameters, in relation to their functional traits, is a relevant issue for studies in forest ecology. The connections of data from field surveys with remotely assessed parameters must be carefully explored. PMID- 27265249 TI - Arthroscopic Suprapectoral and Open Subpectoral Biceps Tenodesis: Radiographic Characteristics. AB - PURPOSE: To provide a detailed account of the location of the long head of the biceps (LHB) tenodesis tunnels using an all-arthroscopic suprapectoral technique in a prospective group of patients. These patients were then compared with a retrospective group of open subpectoral tenodesis patients of similar characteristics. METHODS: Postoperative radiographs from a prospective group of all-arthroscopic suprapectoral LHB tenodeses were compared with a retrospective group of open subpectoral tenodeses. Digital anteroposterior images were used to measure distances from clinically pertinent radiographic landmarks to tenodesis tunnel sites. RESULTS: Forty patients (20 all-arthroscopic, 20 open) met the inclusion criteria. The inferior border of the bicipital groove was located a mean distance of 33.7 +/- 6.9 mm from the top of the humeral head. The mean distance measured in the open group was approximately 28 mm (P < .001) distal compared with the arthroscopic group. The humeral diameter was 7.5 +/- 5.4 mm narrower at the subpectoral tenodesis site (P < .001). All 20 patients in the open subpectoral group had tenodesis tunnels placed distal to the bicipital groove compared with 17 of 20 patients (85%) in the all-arthroscopic group. There were 2 cases of lateral wall cortical reaming during subpectoral tenodesis but no periprosthetic humeral fractures. There were 2 cases of bicortical reaming during the all-arthroscopic tenodesis with no known complications. CONCLUSIONS: The location of biceps tenodesis significantly differs between all-arthroscopic suprapectoral and open subpectoral techniques, and the open subpectoral method achieves fixation in a significantly narrower region of the humerus. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 27265250 TI - Distal Femoral Osteotomy for the Valgus Knee: Medial Closing Wedge Versus Lateral Opening Wedge: A Systematic Review. AB - PURPOSE: (1) To determine the radiographic correction/healing rate, patient reported outcomes, reoperation rate, and complication rate after distal femoral osteotomy (DFO) for the valgus knee with lateral compartment pathology. (2) To summarize the reported results of medial closing wedge and lateral opening wedge DFO. METHODS: We conducted a systematic review of PubMed, MEDLINE, and CINAHL to identify studies reporting outcomes of DFOs for the valgus knee. Keywords included "distal femoral osteotomy," "chondral," "cartilage," "valgus," "joint restoration," "joint preservation," "arthritis," and "gonarthrosis." Two authors first reviewed the articles; our study exclusion criteria were then applied, and the articles were included on the basis relevance defined by the aforementioned criteria. The Methodological Index for Nonrandomized Studies scale judged the quality of the literature. Sixteen studies were relevant to the research questions out of 191 studies identified by the original search. RESULTS: Sixteen studies were identified reporting on 372 osteotomies with mean follow-up of 45 to 180 months. All studies reported mean radiographic correction to a near neutral mechanical axis, with 3.2% nonunion and 3.8% delayed union rates. There was a 9% complication rate and a 34% reoperation rate, of which 15% were converted to arthroplasty. There were similar results reported for medial closing wedge and lateral opening wedge techniques, with a higher conversion to arthroplasty in the medial closing wedge that was confounded by longer mean follow-up in this group (mean follow-up 100 v 58 months). CONCLUSIONS: DFOs for the valgus knee with lateral compartment disease provide improvements in patient-reported knee health related quality of life at midterm follow-up but have high rates of reoperation. No evidence exists proving better results of either the lateral opening wedge or medial closing wedge techniques. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies. PMID- 27265251 TI - Magnetic Resonance Imaging Findings in Symptomatic Patients After Arthroscopic Partial Meniscectomy for Torn Discoid Lateral Meniscus. AB - PURPOSE: To evaluate the change in the thickness and width of the residual meniscus using magnetic resonance imaging (MRI) in patients who underwent arthroscopic partial meniscectomy for discoid lateral meniscus (DLM), to assess whether the degeneration of the articular cartilage in the lateral compartment of the knee progressed, and to evaluate clinical results. METHODS: Among the patients who underwent arthroscopic partial meniscectomy for DLM between January 1997 and December 2011, those who were aged 40 or below at surgery were followed up for at least 3 years, and received at least 2 follow-up MRIs that were retrospectively reviewed. MRIs were done in symptomatic knees. Using MRI, the relative thickness and width were measured in the anterior horn, midportion, and posterior horn. To determine whether the degeneration of the lateral compartment would progress, the articular cartilage was graded based on the Outerbridge classification in MRIs. The clinical results were evaluated using the Lysholm score. RESULTS: A total of 20 patients (21 knees) were included. The average follow-up period was 6.8 years. In residual meniscus, the relative thickness of the midportion decreased from 9.0% +/- 2.4% to 7.3% +/- 2.3% (P < .001), the relative thickness of the anterior horn decreased from 15.6% +/- 4.3% to 14.3% +/ 6.7% (P = .030), and the relative thickness of the posterior horn decreased from 20.0% +/- 4.4% to 16.7% +/- 6.7% (P = .019). A decrease in the relative width was observed in the midportion (12.4% +/- 4.8% to 10.9% +/- 4.9%, P = .003). No significant changes in size were observed in the medial meniscus. A progression of degeneration in the lateral compartment was observed. However, the clinical results did not present significant changes. CONCLUSIONS: In symptomatic patients after arthroscopic partial meniscectomy for DLM, the thickness and width of the residual meniscus decreases over time. The arthritic change of the lateral compartment of the knee progressed. However, the change in the size of the residual meniscus was of unknown clinical significance. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 27265252 TI - [Cerebral infarction after pituitary apoplexy: Description of a case and review of the literature]. AB - Pituitary apoplexy is usually the result of hemorrhagic infarction in a pituitary adenoma. The clinical presentation varies widely and includes asymptomatic cases, classical pituitary apoplexy and even sudden death. Cerebral ischemia due to pituitary apoplexy is very rare. It may be caused by vasospasm or direct compression of cerebral vessels by the tumor. We report a case of pituitary apoplexy associated with cerebral infarction and discuss the relationship between the two events. PMID- 27265253 TI - Interferon-beta therapy specifically reduces pathogenic memory B cells in multiple sclerosis patients by inducing a FAS-mediated apoptosis. AB - Growing evidences put B lymphocytes on a central stage in multiple sclerosis (MS) immunopathology. While investigating the effects of interferon-beta (IFN-beta) therapy, one of the most used first-line disease-modifying drugs for the treatment of relapsing-remitting MS, in circulating B-cell sub-populations, we found a specific and marked decrease of CD27+ memory B cells. Interestingly, memory B cells are considered a population with a great disease-driving relevance in MS and resulted to be also target of B-cell depleting therapies. In addition, Epstein-Barr virus (EBV), associated with MS etiopathogenesis, harbors in this cell type and an IFN-beta-induced reduction of the memory B-cell compartment, in turn, resulted in a decreased expression of the EBV gene latent membrane protein 2A in treated patients. We found that in vivo IFN-beta therapy specifically and highly induced apoptosis in memory B cells, in accordance with a strong increase of the apoptotic markers Annexin-V and active caspase-3, via a mechanism requiring the FAS-receptor/TACI (transmembrane activator and CAML interactor) signaling. Thus, efficacy of IFN-beta therapy in MS may rely not only on its recognized anti-inflammatory activities but also on the specific depletion of memory B cells, considered to be a pathogenic cell subset, reducing their inflammatory impact in target organs. PMID- 27265254 TI - Determination of optimum threshold values for EMG time domain features; a multi dataset investigation. AB - OBJECTIVE: For over two decades, Hudgins' set of time domain features have extensively been applied for classification of hand motions. The calculation of slope sign change and zero crossing features uses a threshold to attenuate the effect of background noise. However, there is no consensus on the optimum threshold value. In this study, we investigate for the first time the effect of threshold selection on the feature space and classification accuracy using multiple datasets. APPROACH: In the first part, four datasets were used, and classification error (CE), separability index, scatter matrix separability criterion, and cardinality of the features were used as performance measures. In the second part, data from eight classes were collected during two separate days with two days in between from eight able-bodied subjects. The threshold for each feature was computed as a factor (R = 0:0.01:4) times the average root mean square of data during rest. For each day, we quantified CE for R = 0 (CEr0) and minimum error (CEbest). Moreover, a cross day threshold validation was applied where, for example, CE of day two (CEodt) is computed based on optimum threshold from day one and vice versa. Finally, we quantified the effect of the threshold when using training data from one day and test data of the other. MAIN RESULTS: All performance metrics generally degraded with increasing threshold values. On average, CEbest (5.26 +/- 2.42%) was significantly better than CEr0 (7.51 +/- 2.41%, P = 0.018), and CEodt (7.50 +/- 2.50%, P = 0.021). During the two-fold validation between days, CEbest performed similar to CEr0. Interestingly, when using the threshold values optimized per subject from day one and day two respectively, on the cross-days classification, the performance decreased. SIGNIFICANCE: We have demonstrated that threshold value has a strong impact on the feature space and that an optimum threshold can be quantified. However, this optimum threshold is highly data and subject driven and thus do not generalize well. There is a strong evidence that R = 0 provides a good trade-off between system performance and generalization. These findings are important for practical use of pattern recognition based myoelectric control. PMID- 27265255 TI - On the difficulty of recognizing distinct Symbiodinium species in mixed communities of algal symbionts. PMID- 27265257 TI - Design and structure-activity relationships of novel inhibitors of human rhinovirus 3C protease. AB - Human rhinovirus (HRV) is a primary cause of common cold and is linked to exacerbation of underlying respiratory diseases such as asthma and COPD. HRV 3C protease, which is responsible for cleavage of viral polyprotein in to proteins essential for viral life-cycle, represents an important target. We have designed proline- and azetidine-based analogues of Rupintrivir that target the P2 pocket of the binding site. Potency optimization, aided with X-ray crystallography and quantum mechanical calculations, led to compounds with activity against a broad spectrum of HRV serotypes. Altogether, these compounds represent alternative starting points to identify promising leads in our continual efforts to treat HRV infections. PMID- 27265258 TI - Synthesis and skin gene analysis of 4'-acetoxy-resveratrol (4AR), therapeutic potential for dermal applications. AB - Resveratrol (RV) 1, a plant polyphenol, has proven effective in commercial products yet drawbacks include low bioavailability due to rapid metabolism. Structural modifications have led to a 4'-acetoxy analog 2 (4AR) now produced using a selective one-step esterification reaction. The one-step synthesis is shown together with expression of skin genes using human dermal models to establish 4AR 2 benefits to skin health. 4AR 2 at 1% in qPCR experiments using a human skin model significantly increased gene expression of the anti-aging factor, SIRT 1 by over 3.3-fold, extracellular matrix proteins collagen III, IV, elastin and tissue inhibitors of metalloproteinases (TIMP 1, 2), anti-oxidants CAT, LOX, superoxide dismutase (SOD 1, 2), metallothioneins (MT1H, MT1H), skin aging biomarkers fibrillin (FBN1), laminin (LAMB1), proliferating cell nuclear antigen (PCNA), skin growth factors (HBEGF, IGF1, NGF and TGF). 4AR 2 also decreased gene expression of inflammatory and skin-aging molecules (IL-1, IL-6, IL-8, COX-2, TNGRSF) and S100 calcium binding proteins A8, A9. These findings suggest that 4AR 2 has potential for topically treatment and prevention of skin aging. PMID- 27265259 TI - Aryl morpholino triazenes inhibit cytochrome P450 1A1 and 1B1. AB - Many cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) inhibitors, such as resveratrol, have planar, hydrophobic, aromatic rings in their structure and exhibit anti-cancer activity. Aryl morpholino triazenes have similar structural features and in addition contain a triazene unit consisting of three consecutive, conjugated nitrogen atoms. Several aryl morpholino triazenes, including 4-[(E)-2 (3,4,5-trimethoxyphenyl)diazenyl]-morpholine (2), were prepared from a reaction involving morpholine and a diazonium ion produced from different aniline derivatives, such as 3,4,5-trimethoxyaniline. The aryl morpholino triazenes were then screened at 100MUM for their ability to inhibit CYP1A1 and CYP1B1 using ethoxyresorufin as the substrate. Triazenes that inhibited the enzymes to less than 80% of the uninhibited enzyme activity were assayed to determine their IC50 value. Compound 2 was the only triazene to inhibit both CYP1A1 and CYP1B1 to the same degree as resveratrol with IC50 values of 10MUM and 18MUM, respectively. Compounds 3 and 6 selectively inhibited CYP1B1 over CYP1A1 with IC values of 2MUM and 7MUM, respectively. Thus, aryl morpholino triazenes are a new class of compounds that can inhibit CYP1A1 and CYP1B1 and potentially prevent cancer. PMID- 27265260 TI - Quality of life and questionnaires in dermatology. PMID- 27265261 TI - Erratum to "Ultrasound in the management of benign cutaneous tumours". PMID- 27265262 TI - Mangrove succession enriches the sediment microbial community in South China. AB - Sediment microorganisms help create and maintain mangrove ecosystems. Although the changes in vegetation during mangrove forest succession have been well studied, the changes in the sediment microbial community during mangrove succession are poorly understood. To investigate the changes in the sediment microbial community during succession of mangroves at Zhanjiang, South China, we used phospholipid fatty acid (PLFA) analysis and the following chronosequence from primary to climax community: unvegetated shoal; Avicennia marina community; Aegiceras corniculatum community; and Bruguiera gymnorrhiza + Rhizophora stylosa community. The PLFA concentrations of all sediment microbial groups (total microorganisms, fungi, gram-positive bacteria, gram-negative bacteria, and actinomycetes) increased significantly with each stage of mangrove succession. Microbial PLFA concentrations in the sediment were significantly lower in the wet season than in the dry season. Regression and ordination analyses indicated that the changes in the microbial community with mangrove succession were mainly associated with properties of the aboveground vegetation (mainly plant height) and the sediment (mainly sediment organic matter and total nitrogen). The changes in the sediment microbial community can probably be explained by increases in nutrients and microhabitat heterogeneity during mangrove succession. PMID- 27265263 TI - Paenibacillus aceti sp. nov., isolated from the traditional solid-state acetic acid fermentation culture of Chinese cereal vinegar. AB - A Gram-stain-negative, rod-shaped, motile, endospore-forming, facultatively anaerobic bacterium, designated strain L14T, was isolated from the traditional acetic acid fermentation culture of Chinese cereal vinegars. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain L14T was affiliated to the genus Paenibacillus, most closely related to Paenibacillus motobuensis MC10T with 97.8 % similarity. Chemotaxonomic characterization supported the allocation of the strain to the genus Paenibacillus. The polar lipid profile of strain L14T contained the major compounds diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The predominant menaquinone was MK-7, and the major fatty acid components were anteiso-C15 : 0, iso-C15 : 0 and C16 : 0. The DNA G+C content of strain L14T was 49.9 mol%. The DNA-DNA relatedness value between strain L14T and P. motobuensis MC10T was 51.2 %. The results of physiological and biochemical tests allowed phenotypic differentiation of strain L14T from closely related species. On the basis of phenotypic and chemotaxonomic analyses, phylogenetic analysis and DNA-DNA relatedness values, strain L14T is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus aceti sp. nov. is proposed. The type strain is L14T (=CGMCC 1.15420T=JCM 31170T). PMID- 27265264 TI - Combined treatment of epigallocatechin gallate and Coenzyme Q10 attenuates cisplatin-induced nephrotoxicity via suppression of oxidative/nitrosative stress, inflammation and cellular damage. AB - Cisplatin (CP), a platinum based anticancer drug is used as one of the first-line therapy for the treatment of different types of solid tumors. However, CP-induced side effects particularly, nephrotoxicity is a major concern. A single nephrotoxic dose (7 mg/kg body weight) of CP was administered in rats with or without, pre and post combined multidoses of epigallocatechin gallate (EGCG) and coenzyme Q10 (CoQ10) (15 and 5 mg/kg body weight respectively). CP administration resulted in marked increase in the nephrotoxic parameters with alterations in the oxidative and nitrosative stress markers. The concentration of inflammatory, as well as apoptotic markers were markedly up-regulated in the kidney of the CP treated group. Furthermore, CP resulted in histological injury in the renal tissues. Combined antioxidant treatment significantly (p < 0.01) attenuated CP induced oxidative stress, nitrosative stress, inflammatory and apoptotic parameters. Moreover, an improvement in the histopathological changes confirmed the nephroprotective effect of antioxidant treatment. In conclusion, our study indicates that the combinatorial multidoses of EGCG and CoQ10 ameliorate the cisplatin-mediated pathogenesis by improving renal oxidative/nitrosative status, inflammation and apoptosis and thus can be used as a promising protective agent to increase the efficacy of the drug by minimizing its major side effect i.e. nephrotoxicity. PMID- 27265265 TI - Red seaweeds for obesity prevention? PMID- 27265266 TI - MicroRNA-mediated maturation of human pluripotent stem cell-derived cardiomyocytes: Towards a better model for cardiotoxicity? AB - Human pluripotent stem cell-derived cardiomyocytes (PSC-CMs) are a promising human cardiac model system for drug development and toxicity screening, along with cell therapy and mechanistic research. The scalable differentiation of human PSCs into CMs provides a renewable cell source that overcomes species differences present in rodent primary CMs. In addition, induced pluripotent stem cell (iPSC) technology allows for development of patient-specific CMs, representing a valuable tool that may lead to better prediction, prevention, and treatment of cardiovascular diseases in this new era of precision medicine. However, the utility of PSC-CMs as an in vitro model is currently limited by their immature phenotype when compared to adult CMs. Recent work has identified microRNAs (miRNAs) as critical regulators of heart development and function. These studies have shown that miRNAs are essential to key processes that span the life cycle of a cardiomyocyte, including proliferation, hypertrophy, beating rhythm, and apoptosis. Importantly, emerging evidence strongly suggests that modulation of select miRNAs can enhance the maturation of PSC-CMs. Here, we review key miRNAs associated with heart development and function, and discuss strategies to promote PSC-CM maturation, focusing on current knowledge surrounding miRNA-based approaches and the application of PSC-CMs with respect to drug screening and disease models. Ultimately, it is likely that combinations of both miRNA and non miRNA maturation strategies may collectively provide the best path forward for producing mature cardiomyocytes in vitro. PMID- 27265267 TI - Clear-cut observation of clearance of sustainable upconverting nanoparticles from lymphatic system of small living mice. AB - The significance of lymphatic system has gathered great attention for immunotechnology related to cancer metastasis and immunotherapy. To develop innovative immunodiagnostics and immunotherapy in in vivo environments, it is very important to understand excretion pathways and clearance of injected cargoes. Herein, we employed Tm(3+)-doped upconverting nanoparticles (UCNPs) with versatile advantages suitable for long-term non-invasive in vivo optical imaging and tracking. Transport and retention of the UCNPs in the lymphatic system were evaluated with high-quality NIR-to-NIR upconversion luminescence (UCL) imaging. We obtained their kinetic luminescence profiles for the injection site and sentinel lymph node (SLN) and observed luminescence signals for one month; we also examined UCL images in SLN tissues, organs, and faeces at each time point. We speculate that the injected UCNPs in a footpad of a small mouse are transported rapidly from the lymphatic system to the blood system and then eventually result in an efficient excretion by the hepatobiliary route. These results will support development of novel techniques for SLN biopsy as well as immunotechnology. PMID- 27265268 TI - Eight-Year Experience with Nocturnal, Every-Other-Day, Online Haemodiafiltration. AB - BACKGROUND: New haemodialysis therapeutic regimens are required to improve patient survival. Longer and more frequent dialysis sessions have produced excellent survival and clinical advantages, while online haemodiafiltration (OL HDF) provides the most efficient form of dialysis treatment. METHODS: In this single-centre observational study, 57 patients on 4-5-hour thrice-weekly OL-HDF were switched to nocturnal every-other-day OL-HDF. Inclusion criteria consisted of stable patients with good prospects for improved occupational, psychological and social rehabilitation. The aim of this study was to report our 8-year experience with this schedule and to evaluate analytical and clinical outcomes. RESULTS: Nocturnal, every-other-day OL-HDF was well tolerated and 56% of patients were working. The convective volume increased from 26.7 +/- 2 litres at baseline to 46.6 +/- 6.5 litres at 24 months (p < 0.01). Increasing the dialysis dose significantly decreased bicarbonate, blood-urea-nitrogen and creatinine values. Predialysis phosphate levels fell markedly with complete suspension of phosphate binders from the second year of follow-up. Although haemoglobin was unchanged, there was a 50.4% reduction in darbepoetin dose at 24 months and a significant decrease in the erythropoietin resistance index. Blood pressure significantly decreased in a few months. Antihypertensive medication requirements were decreased by 60% after 3 months and by 73% after 1 year and this difference was maintained thereafter. CONCLUSIONS: Nocturnal, every-other-day OL-HDF could be an excellent therapeutic alternative since it is well tolerated and leads to clinical and social-occupational rehabilitation with satisfactory morbidity and mortality. These encouraging results strengthen us to continue and invite other clinicians to join this initiative. PMID- 27265269 TI - Inappropriate statistical method in a parallel-group randomized controlled trial results in unsubstantiated conclusions. AB - The conclusions of Cassani et al. in the January 2015 issue of Nutrition Journal (doi: 10.1186/1475-2891-14-5 ) cannot be substantiated by the analysis reported nor by the data themselves. The authors ascribed the observed decrease in inflammatory markers to the components of flaxseed and based their conclusions on within-group comparisons made between the final and the baseline measurements separately in each arm of the randomized controlled trial. However, this is an improper approach and the conclusions of the paper are invalid. A correct analysis of the data shows no such effects. PMID- 27265270 TI - Multiple subcutaneous cholesterol granulomas arising in eruptive vellus hair cysts: A case report and published work review of 11 cases. PMID- 27265271 TI - The Role of Magnetic Resonance Imaging in the Investigation and Management of Invasive Lobular Carcinoma-A 3-Year Retrospective Study in Two District General Hospitals. AB - Invasive lobular carcinoma (ILC) accounts for 5-15% of breast cancers. In comparison to other types of breast cancer, ILC is more likely to be associated with multifocal and contralateral breast involvement as well as a tendency to a diffuse infiltrative growth pattern which can represent a diagnostic challenge. The National Institute of Clinical Excellence guidelines in 2009 recommended the use of magnetic resonance imaging (MRI) in the preoperative assessment of ILC. This study aims to assess compliance with the guidelines in two District General Hospitals and the utility of MRI in the investigation of ILC. All cases of ILC between 2011 and 2013 were retrospectively identified from the pathology database and their breast imaging findings, pathology report, and operative intervention were reviewed. A total of 126 patients were identified with ILC, of these 46 had MRI preoperatively (36.5%). MRI upgraded mammography/ultrasound diagnoses in 10 patients (21.7%). MRI showed multicentric unilateral disease in 17 patients (37.0%) occult on ultrasound/mammogram, with these patients undergoing mastectomy and 16/17 (94.1%) confirmed multifocality on pathology. MRI showed a contralateral lesion in 9 patients (19.6%), four (8.7%) of which were malignant and had bilateral surgery, and five (10.9%) were benign on further imaging/biopsy. MRI also downgraded three patients (6.5%) to unifocal disease with reported multifocal appearances on mammography/ultrasound, and these patients underwent breast-conserving surgery. MRI adds significant additional information to mammograms/ultrasound in ILC and should be undertaken in all such cases preoperatively assuming no contraindication. PMID- 27265272 TI - From the editor. PMID- 27265273 TI - Acute promyelocytic leukemia and differentiation therapy: molecular mechanisms of differentiation, retinoic acid resistance and novel treatments. AB - Incorporation of all-trans-retinoic acid (ATRA) into the treatment of acute promyelocytic leukemia (APL), a type of acute myeloid leukemia (AML), revolutionized the therapy of cancer in the last decade and introduced the concept of differentiation therapy. ATRA, a physiological metabolite of vitamin A (retinol), induces complete clinical remissions (CRs) in about 90% of patients with APL. In contrast to the cytotoxic chemotherapeutics, ATRA can selectively induce terminal differentiation of promyelocytic leukemic cells into normal granulocytes without causing bone marrow hypoplasia or exacerbation of the frequently occurring fatal hemorrhagic syndromes in patients with APL. However, remissions induced by ATRA alone are transient and the patients commonly become resistant to the therapy, leading to relapses in most patients and thus limiting the use of ATRA as a single agent. Therefore, ATRA is currently combined with anthracycline-based chemotherapy, and this regimen dramatically improves patient survival compared to chemotherapy alone, curing about 70% of the patients. However, 30% of APL patients still relapse and die in five years. Recently, arsenic trioxide (As2O3) was proven to be highly effective in inducing CRs not only in APL patients relapsed after ATRA treatment and conventional chemotherapy but also in primary APL patients. Despite the well-documented clinical efficacy of ATRA, molecular mechanisms responsible for development of ATRA resistance are not well understood. Based on in vitro and clinical observations, several mechanisms, including induction of accelerated metabolism of ATRA, decreased bioavailability and plasma drug levels, point mutations in the ATRA-binding domain of promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARalpha) and other molecular events have been proposed to explain ATRA resistance. In this review, the molecular mechanisms of ATRA-induced myeloid cell differentiation and resistance are discussed, together with novel clinical approaches to overcome ATRA resistance in APL. PMID- 27265274 TI - Premarital hemoglobinopathy screening in Kocaeli, Turkey: a crowded industrial center on the north coast of Marmara Sea. AB - OBJECTIVE: Premarital hemoglobinopathy screening is one of the important procedures of hemoglobinopathy control program. This is the first report about the prevalence of hemoglobinopathies in Kocaeli. METHODS: Study covered screening from July 2005 to the end of the December 2008. Under the auspices of the Ministry of Health and Regional Health authorities blood samples of the couples were obtained during admission to the wedding office. Complete blood counts and hemoglobin variant analysis were performed with automatic counter and high pressure liquid chromotography technique. A genetic counseling was given to carriers of abnormal hemoglobins. RESULTS: A total of 88888 people were screened. The frequency of beta -thalassemia trait and sickle cell anemia trait were 0.89% and 0.05% respectively. The frequency of high risk couples was 0.01%. CONCLUSION: The prevalence of beta -thalassemia trait and sickle cell anemia trait was quite low as a reflection of the frequency of eastern and northern Anatolia and migration to Kocaeli from these geographic regions. Although frequency is low, chronic transfusion requirement, high cost of chelating, organ damage, painful crisis and other crisis, availability of stem cell transplantation for a limited number of patients with compatible sibling donors justify premarital screening studies even in less prevalent regions as Kocaeli. PMID- 27265275 TI - Utility of daily catheter-drawn blood cultures to predict catheter-related bacteremia in hematopoietic stem cell transplanted patients. AB - OBJECTIVE: There is no diagnostic tool to identify which bacterial catheter colonization may eventually result in bloodstream infection. We speculated that a faster growth or repeated positivity of serial blood cultures drawn from the catheter might herald catheter-related bacteremia (CRB) before the onset of fever. METHODS: We designed a prospective observational pilot study. All patients who underwent hematopoietic stem cell transplantation (HSCT) were prospectively included in the study over 10 months. Daily catheter-drawn blood cultures (DBC) were performed. We recorded the growth time of each blood culture and bacterial isolation. A fast-growing blood culture (positive <12 hours) or at least 2 positive identical cultures within 4 consecutive days in the DBC were defined as a marker of risk for CRB. The value of this marker to predict CRB was investigated. RESULTS: A total of 82 patients (843 days of catheter) were included in the study. Fast- growing or repeated identical cultures were present in 20 patients; among them, 15 had clinical criteria of CRB. Among 62 patients without fast-growing or repeated identical cultures, 11 met the criteria of CRB. Consequently, for the defined marker of risk, the positive predictive value was 75%, negative predictive value 82%, sensitivity 70%, and specificity 91%. Sixty two blood cultures were needed to detect one case of CRB prior to the onset of fever. CONCLUSION: The use of routinely drawn catheter-blood cultures does not seem to be a useful tool for predicting CRB in HSCT patients. PMID- 27265277 TI - Influence of cholesterol on shape parameters of erythrocytes in hyperglycemic subjects. AB - OBJECTIVE: We determined the morphological changes of erythrocytes in blood samples of diabetic patients with varying levels of hyperglycemia with normo- and hyper-cholesterol concentrations and compared them with cells of healthy subjects. METHODS: The shape analysis was carried out by shape descriptors based on projected area, perimeter and form factor, as measured by the processing of erythrocyte images. Blood smears were collected from normal subjects and from glycemic subjects with normo- and hyper-cholesterol levels. After image processing techniques like edge enhancement, thresholding, filtering, contour extraction, and pattern analysis and recognition, the images were used for shape analysis. RESULTS: The shape parameters, which quantified the changes in erythrocytes in diabetic subjects with normal cholesterol level, showed significant deviation from the shape of normal cells. Cells of diabetic subjects with hyper-cholesterol level showed more deviation than cells with normal cholesterol. CONCLUSION: These changes lead to hyper aggregation and to a decrease in deformability of erythrocytes and hence increase microcirculatory complications. PMID- 27265276 TI - Serum Erythropoietin Levels in Pediatric Hematologic Disorders and Impact of Recombinant Human Erythropoietin Use. AB - OBJECTIVE: In anemic patients, the correlation between serum erythropoietin (sEpo) level and the severity of anemia has been reported previously. However, in different anemia groups, different sEpo levels are measured in patients with similar hemoglobin levels and the etiology of this situation could not be explained. METHODS: We evaluated hemoglobin and sEpo levels in 31 iron deficiency anemia, 26 Fanconi anemia (FA), 21 thallasemia intermedia (TI), 15 acute lymphoblastic leukemia (ALL) patients at presentation and 12 healthy controls. RESULTS: In all disease groups, an inverse linear correlation was shown between hemoglobin and logarhytmic sEpo level. The covariance analyses according to corrected hemoglobin levels exhibited the highest sEpo level in FA, followed by ALL, TI and iron deficiency anemia, sequentialy. CONCLUSION: There was no statisticaly significant difference of sEpo levels in FA patients in terms of androgen treatment and this finding supports that androgen affects erythropoisis directly, and has no effect on erythropoietin. The results indicate that there is no erythropoietin deficiency in the anemia of these patients and the admnistration of exogenous erythropoietin offers no clinical benefit. PMID- 27265278 TI - Role of cytosolic calcium and actin polymerization on agonist-induced secretion by the platelets of liver cirrhosis patients. AB - OBJECTIVE: Variceal bleeding in cirrhosis is mainly due to platelet activation defect and secondary to coagulation defects. Secretion is an important process which release procoagulants for hemostasis. In the present investigation we have evaluated the secretory function of platelets in liver cirrhosis and also the simultaneous changes in cytosolic calcium (Ca2+) and the polymerization of actin in agonist- stimulated platelets in vitro. METHODS: Liver cirrhotic patients with (n=27) or without (n=23) bleeding complication were included in the study. Control subjects (n=50) were also utilized for the study to compare the analytical data. Platelets were activated by collagen in vitro and the secretory response was assessed by the levels of nucleotides, serotonin, pyrophosphate (PPi) and inorganic phosphate (Pi) secreted into the extracellular fluid of the platelet suspension at various time intervals. During the course of secretion the alteration in the polymerization of actin was monitored simultaneously with the changes in the cytosolic Ca2+ level. RESULTS: The secretory response of platelets to collagen was significantly low in both bleeders and non-bleeders when compared to that of normal subjects. During secretion, low level of actin polymerization and cytosolic Ca2+ level were observed in the platelets of bleeders than in non bleeders and normal subjects. The low secretory capacity of cirrhosis platelets could be correlated with low levels of actin polymerization and cytosolic Ca2+. The alterations were highly significant in the platelets of bleeders when compared to those of non-bleeders. CONCLUSION: The defective secretory activity of platelets in cirrhosis bleeders might be partly due to low polymerization of G actin to F-actin which is required for platelet shape change and for the release of procoagulants. Cytosolic Ca2+ level seems to influence actin polymerization and thereby impairs platelet secretory response to agonists in cirrhosis patients with bleeding complication. PMID- 27265279 TI - The association of bladder myeloid sarcoma and unclassified myelodysplastic/myeloproliferative disease. AB - Myeloid sarcoma of urinary bladder is a rare disorder. We report a 71-year old man with hematuria. He was also under follow up for unclassified myeloproliferative/ myelodysplastic disorder, diagnosed 2 months ago. Abdominal ultrasonography and computed tomography findings were normal. Diagnostic cystoscopy revealed patchy areas of mucosal swelling with hyperemia. Histopathological examination of biopsies demonstrated a neoplasm composed of blasts showing myeloperoxidease positivity by immunohistochemistry. To our knowledge, current case is the first case of myeloid sarcoma without evidence of a mass lesion in the urinary bladder with a concurrent diagnosis of myelodysplastic /myeloproliferative disease, unclassifiable. PMID- 27265280 TI - Hyperfibrotic myelodysplastic syndrome: a report of three cases from north India. AB - Extensive fibrosis in myelodysplastic syndromes (MDS) is distinctly infrequent. Herein, we report three rare cases of hyperfibrotic MDS. This entity should be classified separately in the chronic myeloproliferative disease (CMPD)-MDS group due to variable clinical presentation and poor prognosis. PMID- 27265281 TI - Acute myeloid leukemia following radioactive iodine therapy for papillary carcinoma of the thyroid. AB - Radioactive iodine (RAI) therapy plays an important role in the management of thyroid malignancies. Leukemia is a very rare complication of radioactive therapy. There are very few case reports with doses below 100 mCi causing leukemia. We report a case of papillary carcinoma of the thyroid treated with 80 mCi RAI who later developed acute myeloid leukemia. Thus, all patients with thyroid carcinoma treated with RAI should undergo periodic hematological examinations irrespective of RAI dose. PMID- 27265282 TI - Compound heterozygosity for Hb D-Punjab / beta-thalassemia and blood donation: case report. PMID- 27265283 TI - Leishmaniasis in Yemeni children. PMID- 27265284 TI - Premarital and antenatal screening of Hb-Los Angeles. PMID- 27265285 TI - Gingival and lip hypertrophy induced by cyclosporin A treatment in an aplastic anemia patient. PMID- 27265287 TI - Telomere and telomerase in hematologicalmalignancies. PMID- 27265286 TI - The Nature of Social Positive Illusory Bias: Reflection of Social Impairment, Self-Protective Motivation, or Poor Executive Functioning? AB - The present study examined if a social positive illusory bias (PIB) is: a) simply a reflection of low adult-rated social acceptance, b) evident when children's perceived social acceptance is measured implicitly, and c) directly relates to impaired executive functioning (EF). Participants were 8 to 12 year-old children (N = 120; 55 boys and 65 girls) with and without clinical symptoms of attention deficit/hyperactivity disorder (ADHD). Ratings of the child's social acceptance were obtained from an adult and the child using the Self-Perception Profile for Children (Harter 2012); social bias was calculated as the discrepancy between standardized adult- and child-ratings. Children also completed a reaction time measure to assess implicit perceptions of social acceptance and a battery of EF measures. Depression symptoms were assessed based on parent report. Group comparisons were focused on the presence or absence of social PIB rather than on ADHD diagnostic status. Relative to non-PIB children, those with a social PIB were significantly higher in self-reported social acceptance, but significantly lower on adult reports and implicit perceived social acceptance; these children also were significantly higher in depression symptoms. EF impairments were indirectly related to social PIB as a function of adult-rated social impairment. Results suggest that social PIB is not merely a reflection of low adult-ratings of social acceptance. However, the high explicit self-reports of social acceptance in children with a social PIB are not fully consistent with their implicit self-perceptions of social acceptance. Results are discussed in light of the self-protective and cognitive deficits hypotheses regarding the nature of social PIB. PMID- 27265288 TI - Five-year evaluation of premarital screening program for hemoglobinopathies in the province of Mersin, Turkey. AB - The prevalences of hemoglobin S (HbS) and beta-thalassemia (beta-thal) are high in Mersin, Turkey. In this study, the results of a five-year premarital screening program in Mersin province are reported. A total of 79,000 persons including 31,498 couples were screened in this program. Hematological analyses and electrophoresis were done to identify carriers. The results were given confidentially and at-risk couples were counselled on reproductive options and prenatal diagnosis. The carrier rates of hemoglobins (Hb) (HbS, HbD, HbE) and of beta-thal were 1.21%, 0.17%, 0.04% and 2.04%, respectively. One hundred and thirty-four couples were at-risk, of whom 67.2% had health insurance. Twenty seven couples did not become pregnant, six were divorced and 11 could not be reached. Of the 135 pregnancies, 80 had prenatal diagnosis. Five stillbirths occurred, and 18 homozygous babies were born to couples that did not seek prenatal diagnosis. Two families with prenatal diagnosis had affected babies: one was a late referral and the other due to religious reasons. For a successful screening program, emphasis must be on extensive and intensive informative programs for the public as a whole. Prenatal diagnosis should be offered free of charge as a basic public service. For a healthy population, knowledge and a shared responsibility between the public and the government are necessary. PMID- 27265289 TI - Effects of beta-adrenergic receptor blockade on stress-induced changes in hematological parameters of rats. AB - This study was carried out to examine the effects of acute and chronic stress on hematological parameters in combination with beta-adrenergic receptor blockade in rats. In the present study, acute stress is a form of short-term stress induced by a single footshock session, and chronic stress is a form of long-term stress induced by multiple and repetitive footshock sessions. Male Wistar rats were treated with propranolol (5 mg/kg s.c.) and were subjected to an acute stress [intermittent session of footshock: 0.5 mA, during 60s (5s shock, 5s pause) at one and three days after the moment of propranolol administration] and to a chronic stress [intermittent session of footshock: 0.5 mA, during 60s (5s shock, 5s pause) over three consecutive days from the moment of propranolol administration]. Control group rats were subjected to the same conditions without the propranolol administration and were treated with saline solution. Four days after the drug administration, we assessed the number of total erythrocytes, the erythrocyte indexes (mean cell volume, MCV; mean cell hemoglobin, MCH; mean cell hemoglobin concentration, MCHC) and the number of thrombocytes. The results indicate that hematological parameters differed under acute and chronic stress conditions in combination with adrenergic receptor blockade. beta-adrenergic receptor blockade with propranolol enhances the total number of erythrocytes under acute stress influences and the total number of thrombocytes under chronic stress influences. Acute and chronic stress in combinaton with beta-adrenergic blockade has no significant effect on erythrocyte indexes. Propranolol administration in low doses during different forms of stress could prevent erythrocyte disorders after stress exposure and symptoms in post-traumatic stress disorders. Propranolol markedly suppressed the tachycardia induced by footshock stress after chronic administration. On the whole, the obtained data indicate the important role of beta-adrenoreceptor mechanisms in the regulation of erythrocyte dynamics. PMID- 27265290 TI - Plasma levels of thrombin activatable fibrinolysis inhibitor antigen in active and inactive inflammatory bowel disease. AB - BACKGROUND: The clinical course of patients with inflammatory bowel disease (IBD) is frequently complicated by thromboembolic events and may involve the arterial and venous systems. Although not uniformly documented, several studies document substantial alterations in markers of coagulation and fibrinolysis in patients with IBD. METHODS: 45 patients with IBD (31 UC,14 CD) were included in the study. Age and sex matched 16 volunteers were used as a control group. TAFI antigen was determined using an ELISA kit VisuLiseTM for quantitative measurement. RESULTS: Inflammatory parameters such as white blood cell, platelet levels, erythrocyte sedimentation rate, C-reactive protein were found to be significantly higher in active disease group compared to inactive patients. Coagulation parameters of prothrombin time, activated partial thromboplastin time and d-dimer levels showed no significant difference between active and inactive IBD. Fibrinogen levels were significantly higher in clinically active IBD patients. Plasma TAFI levels demonstrated no significant difference between active and control, inactive and control as well as active and inactive groups. We observed no significant changes in levels of beta-TG and PF-4 between active and inactive disease group. CONCLUSIONS: We studied plasma TAFI levels in IBD. In conclusion, plasma TAFI levels does not appear to represent to be a marker of activation in IBD in contrast to literature. So further studies covering more patients with different clinic and disease activity status might improve the perspective on this issue. PMID- 27265291 TI - Frequency of five thrombophilic polymorphisms in the Egyptian population. AB - This study was conducted to evaluate the frequency of FV1691 G-A, FV4070 A-G, PT20210 G-A, EPCR 23 gene bp insertion and ACE gene 300 bp deletion among healthy Egyptians. One hundred and eighty eight healthy Egyptians were included to the study. Previously reported molecular techniques were used for the determination of mutations. Thirthy one individuals had FV1691 G-A (16.5%) mutation with an allele frequency of 0.09. R2 and R3 haplotypes were found in 21 (11.2%) and 4 (2.1%) individuals, respectively. Only one healthy individual had EPCR gene 23 bp insertion (0.53%) and two individuals (1.06%) had PT20210 G-A mutation, respectively. The ACE gene -300 bp del in homozygous state was present in 92 (48.9%) individuals. The frequency of D allele was 0.718. Our preliminary data revealed that FV1691 G-A mutation is very frequent among Egyptians and it will be meaningfull to study the mutation also in the thrombotic events in Egypt. PMID- 27265292 TI - Cytomegalovirus antigenemia is observed more frequently following allogeneic peripheral blood stem cell transplantation compared to bone marrow transplantation. AB - One of the major complications following hematopoietic stem cell transplantation (HSCT) is cytomegalovirus (CMV) infection. In our institution, three methods have been applied routinely for the diagnosis of CMV antigenemia (CMV-Ag): 1. Direct immunofluorescence microscopic (IFM) examination; 2. Flow cytometric (FC) analysis; and 3. Serological investigation. We were able to detect CMV-Ag by FC in 18 out of 75 transplanted cases. In 14 of these, positivity was confirmed by IFM as well. CMV-Ag was detected as positive by FC in samples from peripheral blood (14 cases) and/or bronchoalveolar lavage (BAL) fluid (4 cases). Eighteen patients had been transplanted [peripheral blood stem cell transplantation (PBSCT)/bone marrow transplantation (BMT): 16/2]. CMV-Ag was detected in 34% of PBSCTs and 7% of BMTs (p<0.008). Antigenemia was observed at a median of 4.5 months. In most of the patients, graft-versus-host disease (GVHD) was accompained by CMV-Ag. The ratio of acute GVHD/chronic GVHD was 6/10. Out of 18 CMV-Ag positive patients, 16 also had signs of infection. They were all positive by IFM as well. The two methods of CMV-Ag detection were correlated (r=0.619, p<0.0001). An important finding is the higher frequency of CMV-Ag and GVHD in patients who had received PBSCT. PMID- 27265293 TI - A rare familial thrombocytopenia: May-Hegglin anomaly report of two cases and review of the literature. AB - May-Hegglin anomaly is a hereditary thrombocytopenia associated with giant platelets and large basophilic, cytoplasmic inclusion bodies (resembling Dohle bodies) in the granulocytes. Patients may experience easy bruising, recurrent epistaxis, gingival bleeding, menorrhagia and sometimes excessive bleeding associated with surgical procedures. Failure to appropriately diagnose May Hegglin anomaly could result in inappropriate treatment. In states of chronic thrombocytopenia associated with large platelets, including chronic idiopathic thrombocytopenic purpura, May-Hegglin anomaly should be considered in the differential diagnosis. In this case report, we present a five-year-old girl previously followed as idiopathic thrombocytopenic purpura without bleeding symptoms and a 14-year-old boy who were diagnosed with May-Hegglin anomaly. PMID- 27265294 TI - t(1;3)(p36;p21): presentation of a patient with MDS/AML (M2) and review of the literature. AB - t(1;3)(p36;p21) is a recurrent reciprocal translocation found in a subset of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and poor prognosis. In the literature, some authors have suggested that this recurrent translocation is closely associated with prior chemotherapy including alkylating agents in various hematologic malignancies. We identified a recurring translocation, t(1;3)(p36;p21), in our patient with MDS/AML(M2), although she had not been given any kind of treatment previously. PMID- 27265295 TI - Platelet satellitism in a pregnant woman. AB - t(1;3)(p36;p21) is a recurrent reciprocal translocation found in a subset of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and poor prognosis. In the literature, some authors have suggested that this recurrent translocation is closely associated with prior chemotherapy including alkylating agents in various hematologic malignancies. We identified a recurring translocation, t(1;3)(p36;p21), in our patient with MDS/AML(M2), although she had not been given any kind of treatment previously. PMID- 27265296 TI - Megadose methylprednisolone (MDMP) treatment. PMID- 27265297 TI - Improvements and important considerations for the 5-choice serial reaction time task-An effective measurement of visual attention in rats. AB - BACKGROUND: The 5-choice serial reaction time task (5-CSRTT) is an automated operant conditioning task that measures rodent attention. The task allows the measurement of several parameters such as response accuracy, speed of processing, motivation, and impulsivity. The task has been widely used to investigate attentional processes in rodents for attention deficit and hyperactivity disorder and has expanded to other illnesses such as Alzheimer's disease, depression, and schizophrenia. NEW METHOD: The 5-CSRTT is accompanied with two significant caveats: a time intensive training period and largely varied individual rat capability to learn and perform the task. Here we provide a regimented acquisition protocol to enhance training for the 5-CSRTT and discuss important considerations for researchers using the 5-CSRTT. RESULTS: We offer guidelines to ensure that inferences on performance in the 5-CSRTT are in fact a result of experimental manipulation rather than training differences, or individual animal capability. According to our findings only rats that have been trained successfully within a limited time frame should be used for the remainder of the study. COMPARISON WITH EXISTING METHOD(S): Currently the 5-CSRTT employs a training period of variable duration and procedure, and its inferences on attention must overcome heterogeneous innate animal differences. CONCLUSIONS: The 5-CSRTT offers valuable and valid insights on various rodent attentional processes and their translation to the underpinnings of illnesses such as schizophrenia. The recommendations made here provide important criteria to ensure inferences made from this task are in fact relevant to the attentional processes being measured. PMID- 27265300 TI - Mechanochemical and thermal formation of 1H-benzotriazole coordination polymers and complexes of 3d-transition metals with intriguing dielectric properties. AB - Liquid-assisted grinding (LAG) reactions have been successfully applied to achieve a series of complexes and coordination polymers based on divalent 3d transition metal chlorides (TM chlorides) and the aromatic ligand 1H benzotriazole (BtzH). The obtained substances were investigated via single crystal X-ray, powder X-ray determination and simultaneous DTA/TG analysis as model compounds for structural and chemical influences on their dielectric properties. Depending on the synthesis method, different constitutions and structures are observed. Two polymorphous forms of the 1D polymer [MnCl2(BtzH)2] (1 and 2) as well as the complexes [ZnCl2(BtzH)2].BtzH (3) and [CoCl2(BtzH)2].BtzH (4) have been obtained as phase-pure bulk substances via the mechanochemical LAG route, and even single crystals are available. For comparison, thermal reactions were also carried out and have led to the formation of the neutral complexes: [CoCl2(BtzH)2] (5) and [CoCl2(BtzH)4].4BtzH (6), [ZnCl2(BtzH)2] (7) and the anionic complex BtzH2[CoCl3BtzH] (8). In addition, thermal treatment of 3 yields the benzotriazolium salt {(BtzH)2H}Cl (9). The transition metal compounds were additionally analysed regarding their dielectric properties by frequency-dependent as well as temperature-dependent permittivity investigations. It is intriguing that compounds 1 and 3 show remarkably low dielectric constants and loss factors up to 50 degrees C highlighting them as potential "low-k materials". PMID- 27265298 TI - Impact of organic mercury exposure and home delivery on neurodevelopment of Amazonian children. AB - In the transitioning Amazon, we addressed birth environment (home vs hospital) and associated perinatal organic-Hg exposures: methylmercury (MeHg) from maternal fish consumption and ethylmercury (EtHg) from pediatric Thimerosal-containing vaccines (TCVs) taken systematically during hospital delivery. We studied 365 children in relation to linear growth at 60 months and neurodevelopment (milestone achievements, Bayley Scale of Infant Development/BSID at 24 months, and Stanford-Binet intelligence tests at 60 months). Mothers delivered in hospitals vs those gave birth at home had significantly (p<0.0001) lower hair-Hg (HHg) concentrations (12.2 vs 23.9MUg/g respectively) and shorter length of breastfeeding (8.5 vs 9.7 months respectively). Home-born children had significantly (p<0.0001) higher HHg (7.1MUg/g) than hospital-born children (4.6MUg/g). Hospital-born children also had significantly earlier (p<0.0001) hepatitis B vaccine than home-born children (1.5 vs 24.1days respectively) and higher (p<0.0001) exposures to total TCV-EtHg (75.8 vs 49.3MUg respectively). Neither anthropometric indices nor neurodevelopment (except for fluid reasoning) were directly affected by birth environment. The percentage of hospital-born children with BSID (MDI or PDI) scores <80 was not significantly different from those born at home. In spite of the differences in HHg and EtHg levels between hospital-born and home-born children, no impact on neurodevelopment was observed. PMID- 27265301 TI - Management of invasive and non-invasive breast cancer in the United States and China. PMID- 27265299 TI - Exposure to non-persistent pesticides and thyroid function: A systematic review of epidemiological evidence. AB - Numerous pesticides are recognized for their endocrine-disrupting properties. Non persistent pesticides such as organophosphates, dithiocarbamates and pyrethroids may interfere with thyroid function as suggested by animal studies. However, the influence of chronic exposure to these compounds on thyroidal functions in humans remains to be determined. The present study aimed to review epidemiological evidence for an association between exposure to non-persistent pesticides and circulating levels of thyroid hormones (thyroxin [T4] and triiodothyronine [T3]) and thyroid-stimulating hormone (TSH). A systematic review was conducted using MEDLINE, SCOPUS and Virtual Health Library (BVS) databases. Articles were limited to original studies and reports published in English, Portuguese or Spanish. Nineteen epidemiological studies were identified, 17 of which were cross sectional, 14 were of occupationally exposed workers and 11 used exposure biomarkers. Fungicides and organophosphates (OP) insecticides were the most studied pesticides. Although methodological heterogeneity between studies was noted, particularly regarding study design, exposure assessment, and control of confounding, most of them showed associations with changes in T3 and T4, and/or TSH levels, while results from a few of these are consistent with experimental data supporting the findings that non-persistent pesticide exposure exerts hypothyroid-like effects. However, reporting quality was moderate to poor in 50% of the studies, particularly regarding method of selection of participants and discussion of external validity. Overall, current knowledge regarding the impact of non-persistent pesticides on human thyroid function is still limited. Given the widespread use of pesticides, future research should assess effects of exposure to currently-used pesticides in cohort studies combining comprehensive questionnaire-based assessment and biomarkers. Investigators need to pay particular attention to exposure during critical windows of brain development and exposure in agricultural populations. PMID- 27265302 TI - Advances in the surgical treatment of breast cancer. AB - Breast cancer has become the top malignant neoplasm in Chinese women with an increasing risk of morbidity and mortality. As a crucial part of comprehensive treatment of breast cancer, breast surgical technique is ceaselessly ameliorating and enriching its features. With the purpose of achieving minimal surgical intervention and satisfactory cosmetic results, the trend of mammary surgery is focusing on minimally invasive treatment and aesthetics in the 21st century. This article gives an overview of the most representative surgical procedures, such as breast conservative surgery, sentinel lymph node dissection, oncoplastic technique and breast reconstructive surgery. PMID- 27265303 TI - HER2-positive breast cancer, how far away from the cure?-on the current situation of anti-HER2 therapy in breast cancer treatment and survival of patients. AB - With the diagnosis and treatment of tumor enter into the area of precision medical, based on selected targeted molecular typing of patients with individualized diagnosis and treatment play an important role. HER gene encoded epidermal growth factor receptor 2 (HER2) leading to increased early distant metastasis of breast cancer in patients and poor prognosis. However, a number of clinical studies provided evidence-based anti-HER2 targeted therapy and confirmed the benefit of anti-HER2 targeted therapy in patient survival. In recent years, through the tireless efforts of scholars in the field of breast cancer in our country, the whole diagnosis and treatment of breast cancer has accomplished an international standard. But based on a variety of factors, the anti-HER2 targeted therapy between China and the developed countries, and between different areas in China still exists certain gaps, is now a problem need to be solved. This article will analyzing the diagnostic and treatment on HER2-positive breast cancer in the United States and China, exploring reasons and looking for answers to narrow down the gap in the treatment of HER2-positive breast cancer between China and the United States. Improve the anti-HER2 targeted therapy in our country, let the patients get maximum benefit from anti-HER2 targeted therapy. PMID- 27265304 TI - Genetic testing for hereditary breast cancer in Asia-moving forward. AB - Genetic screening for hereditary breast and ovarian cancer (HBOC) has gained much attention for the past decades. With the development of advanced sequencing technology, other novel breast cancer associated susceptibility genes, other than BRCA genes, have been identified recently. The prevalence of BRCA mutation is known to be different in the West and in the East, therefore it is important to understand the mutation spectrum locally and in Asia to improve early diagnosis and clinical management of hereditary breast cancer in the region. In this editorial, we sought to highlight the need of genetic screening in HBOC, and also highlight specific issues within Asia which may need to be addressed to help popularize its appropriate use in this region. PMID- 27265306 TI - Contribution of forest foods to dietary intake and their association with household food insecurity: a cross-sectional study in women from rural Cameroon. AB - OBJECTIVE: To determine the contribution of forest foods to dietary intake and estimate their association with household food insecurity. DESIGN: Cross sectional survey conducted among 279 households. Using a 7 d recall questionnaire, information on household food consumption was collected from women and used to determine the household dietary diversity score, food variety score and forest food consumption score (FFCS). Household Food Insecurity Access Scale (HFIAS) score was determined and Spearman rank correlation was used to establish the relationship between consumption of forest foods and HFIAS score. Women's dietary intake was estimated from two 24 h recalls. The contribution of forest foods to women's nutrient intakes was calculated and women's nutrient intakes were compared with estimated average nutrient requirements. SETTING: Rural forest dependent households in twelve villages in eastern and southern Cameroon. SUBJECTS: Household heads and their non-pregnant, non-lactating spouses. RESULTS: Forty-seven unique forest foods were identified; of these, seventeen were consumed by 98 % of respondents over the course of one week and by 17 % of women during the two 24 h recall periods. Although forest foods contributed approximately half of women's total daily energy intake, considerably greater contributions were made to vitamin A (93 %), Na (100 %), Fe (85 %), Zn (88 %) and Ca (89 %) intakes. Despite a highly biodiverse pool of foods, most households (83 %) suffered from high food insecurity based on the HFIAS. A significant inverse correlation was observed between the HFIAS score and the FFCS (r 2=-0.169, P=0.0006), demonstrating that forest foods play an important role in ensuring food security in these forest-dependent communities. CONCLUSIONS: Forest foods are widely consumed by forest-dependent communities. Given their rich nutrient content, they have potential to contribute to food and nutrition security. PMID- 27265305 TI - Co-expression of the proteinase inhibitors oryzacystatin I and oryzacystatin II in transgenic potato alters Colorado potato beetle larval development. AB - Colorado potato beetle (CPB; Leptinotarsa decemlineata Say, Coleoptera: Chrysomelidae) has shown a remarkable adaptability to a variety of control measures. Although oryzacystatin I and II (OCI and OCII) have potential in controlling pests that use cysteine proteinases for food digestion, expression of a single OC gene in potato exhibited a minimal or no effect on CPB fitness traits. The aim of this study was to examine the effect of coexpressed OCI and OCII in potato (Solanum tuberosum L.) cultivars Desiree, Dragacevka and Jelica on CPB larvae. Growth parameters, consumption rates and food utilization, as well as activity of proteases of CPB larvae were assayed. Second and third instar larvae fed on transformed leaves molted earlier and had higher relative growth and consumption rates than larvae fed on nontransformed leaves, while efficiency of food utilization was unaffected. In contrast, fourth instar maximum weight gain and amount of leaves consumed were about 20% lower for the larvae fed on transgenic potato. Analysis of total protease activity of third instar larvae revealed reduction in overall proteolytic activity measured by azocasein hydrolysis, accompanied with inhibition of cysteine proteinase activity 24 h after ingestion of potato leaves expressing OCI and OCII. However, after long term feeding on transformed leaves proteolytic activities of larvae became similar to the controls. Although feeding on OCI/OCII leaves did not affect larval survival, coexpression of OC genes reduced the development time and thus significantly decreased plant damage caused by CPB larvae. PMID- 27265307 TI - Multiple squamous cells in thyroid fine needle aspiration: Friends or foes? AB - BACKGROUND: Abundant squamous cells are rarely encountered in thyroid FNA with only few case reports noted in the literature. Their presence and cytologic features may pose a diagnostic dilemma and challenges for proper classification and follow-up. We intend to gain more insight into the frequency of this finding and its clinical significance. DESIGN: Our electronic records were searched over 16 years to reveal 15 thyroid FNAs with abundant squamous cells. The available cytology and surgical resection slides were reviewed and radiologic records and clinical follow-up was documented. RESULTS: Only 15 out of 8811 thyroid FNAs from our department contained predominantly squamous cells (0.17%) of which two were interpreted as nondiagnostic, four as atypical, eight as benign, and one malignant. Surgical follow-up was available in eight cases only with benign lesions representing the majority of the cases (squamous metaplasia in Hashimoto thyroiditis, benign epidermoid/branchial cleft or thyroglossal duct cysts, and one case squamous cell carcinoma). The cases without surgical resection were stable on subsequent ultrasound studies. CONCLUSION: Thyroid aspirates with predominance of squamous cells cannot be classified in the current Bethesda categories. Even when interpreted as atypical or equivocal, the squamous cells present in our small case series were mostly benign. The only malignant case was easily identified cytologically because of its higher degree of differentiation. The most common pitfall for atypical squamous cells in these aspirates was squamous metaplasia in the setting of Hashimoto thyroiditis and degenerative changes. Diagn. Cytopathol. 2016;44:676-681. (c) 2016 Wiley Periodicals, Inc. PMID- 27265308 TI - Chemically modified graphene films for high-performance optical NO2 sensors. AB - Various graphene-based gas sensors that operate based on the electrical properties of graphene have been developed for accurate detection of gas components. However, electronic graphene-based gas sensors are unsafe under explosive atmospheres and sensitive to electromagnetic interference. Here, a novel optical graphene-based gas sensor for NO2 detection is established based on surface chemical modification of high-temperature-reduced graphene oxide (h-rGO) films with sulfo groups. Sulfo group-modified h-rGO (S-h-rGO) films with a thickness of several nanometers exhibit excellent performance in NO2 detection at room temperature and atmospheric pressure based on the polarization absorption effect of graphene. Initial slope analysis of the S-h-rGO sensor indicates that it has a limit of detection of 0.28 ppm and a response time of 300 s for NO2 gas sensing. Furthermore, the S-h-rGO sensor also possesses the advantages of good linearity, reversibility, selectivity, non-contact operation, low cost and safety. This novel optical gas sensor has the potential to serve as a general platform for the selective detection of a variety of gases with high performance. PMID- 27265311 TI - Novel chitin/chitosan-glucan wound dressing: Isolation, characterization, antibacterial activity and wound healing properties. AB - Chitin/chitosan-glucan complex (ChCsGC) was isolated from Schizophyllum commune (S. commune) and dissolved for the first time in precooled (-15 degrees C) 8wt.% urea/6wt.% NaOH aqueous solution. Novel nonwoven microfiber mats were fabricated by wet-dry-spinning technique and evaluated the mechanical of fabrics mats and surface morphology. Isolated and nonwoven mat were characterized employing FTIR ATR, Optical microscope, TGA, DSC, H/C NMR, SEM and XRD techniques. According to the physical/chemical characterization measurements we can assumed that, the net and the novel dressing mats have the same chemical structure with slightly changes in the thermal stability for the dressing mats.The biological activity of the nonwoven ChCsGC fabric was tested against different types of bacteria exhibiting excellent antibacterial activity. Cell viability of the plain complex and nonwovens mats were evaluated utilizing mouse fibroblast cell line varying concentrations and treatment time. ChCsGC did not show any cytotoxicity against mouse fibroblast cells and the cell-fabrics interaction was also investigated using fluorescence microscope. The novel ChCsGC nonwovens exhibited excellent surgical wound healing ability when tested using rat models. PMID- 27265312 TI - Solid state drug-polymer miscibility studies using the model drug ABT-102. AB - Amorphous solid dispersions typically suffer storage stability issues due to: their amorphous nature, high drug loading, uneven drug:stabilizer ratio and plasticization effects as a result of hygroscopic excipients. An extensive solid state miscibility study was conducted to aid in understanding the mechanisms involved in drug/stabilizer interactions. ABT-102 (model drug) and nine different polymers with different molecular weights and viscosities were selected to investigate drug/polymer miscibility. Three different polymer:drug ratios (1:3, 1:1 and 3:1, w/w) were analyzed using: DSC, FTIR and PXRD. Three different techniques were used to prepare the amorphous solid dispersions: serial dilution, solvent evaporation and spray drying. Spray drying was the best method to obtain amorphous solid dispersions. However, under certain conditions amorphous formulations could be obtained using solvent evaporation. Melting point depression was used to calculate interaction parameters and free energy of mixing for the various drug polymer mixtures. The spray dried solid dispersions yielded a negative free energy of mixing which indicated strong drug-polymer miscibility compared to the solvent evaporation and serial dilution method. Soluplus was the best stabilizer compared to PVP and HPMC, which is probably a consequence of strong hydrogen bonding between the two CO moieties of soluplus and the drug NH moieities. PMID- 27265309 TI - High-throughput screening in the C. elegans nervous system. AB - The nematode Caenorhabditis elegans is widely used as a model organism in the field of neurobiology. The wiring of the C. elegans nervous system has been entirely mapped, and the animal's optical transparency allows for in vivo observation of neuronal activity. The nematode is also small in size, self fertilizing, and inexpensive to cultivate and maintain, greatly lending to its utility as a whole-animal model for high-throughput screening (HTS) in the nervous system. However, the use of this organism in large-scale screens presents unique technical challenges, including reversible immobilization of the animal, parallel single-animal culture and containment, automation of laser surgery, and high-throughput image acquisition and phenotyping. These obstacles require significant modification of existing techniques and the creation of new C. elegans-based HTS platforms. In this review, we outline these challenges in detail and survey the novel technologies and methods that have been developed to address them. PMID- 27265313 TI - A novel concept for the treatment of couperosis based on nanocrystals in combination with solid lipid nanoparticles (SLN). AB - For the post laser treatment of couperosis a new dermal formulation was developed combining three actives: vitamin K1, A1 and rutin, where both vitamins were incorporated into solid lipid nanoparticles (SLN) and the poorly soluble antioxidant rutin formulated as nanocrystal. All three formulations were stable over 6 months either on their own or after their incorporation into a hydrogel. Vitamin A1 at 0.3% in emulsions shows local skin irritation due to very rapid release. By forming SLN, prolonged release with less irritation potential but deeper penetration was achieved in porcine ear skin. Due to the nanosized rutin, the new hydrogel showed clearly increased antioxidant activity, representing a stronger protection potential against reactive oxygen species (ROS), compared to marketed anti-redness products with rutin as raw drug powder or water-soluble derivative. In addition, rutin nanocrystals showed up to 5 times pronounced penetration compared to MUm-sized raw drug powder. The orientating in-vivo case study revealed a three to six times faster recovery after laser treatment of couperosis by twice daily application of the new hydrogel, regarding scabbed-over areas and erythema. Continued use of the new gel also showed preventive properties against recurrences of veins for at least 8 month. PMID- 27265314 TI - Comparison of the cohesion-adhesion balance approach to colloidal probe atomic force microscopy and the measurement of Hansen partial solubility parameters by inverse gas chromatography for the prediction of dry powder inhalation performance. AB - The abilities of the cohesive-adhesive balance approach to atomic force microscopy (AFM) and the measurement of Hansen partial solubility parameters by inverse gas chromatography (IGC) to predict the performance of carrier-based dry powder inhaler (DPI) formulations were compared. Five model drugs (beclometasone dipropionate, budesonide, salbutamol sulphate, terbutaline sulphate and triamcinolone acetonide) and three model carriers (erythritol, alpha-lactose monohydrate and d-mannitol) were chosen, giving fifteen drug-carrier combinations. Comparison of the AFM and IGC interparticulate adhesion data suggested that they did not produce equivalent results. Comparison of the AFM data with the in vitro fine particle delivery of appropriate DPI formulations normalised to account for particle size differences revealed a previously observed pattern for the AFM measurements, with a slightly cohesive AFM CAB ratio being associated with the highest fine particle fraction. However, no consistent relationship between formulation performance and the IGC data was observed. The results as a whole highlight the complexity of the many interacting variables that can affect the behaviour of DPIs and suggest that the prediction of their performance from a single measurement is unlikely to be successful in every case. PMID- 27265315 TI - Partitioning of Organic Ions to Muscle Protein: Experimental Data, Modeling, and Implications for in Vivo Distribution of Organic Ions. AB - The in vivo partitioning behavior of ionogenic organic chemicals (IOCs) is of paramount importance for their toxicokinetics and bioaccumulation. Among other proteins, structural proteins including muscle proteins could be an important sorption phase for IOCs, because of their high quantity in the human and other animals' body and their polar nature. Binding data for IOCs to structural proteins are, however, severely limited. Therefore, in this study muscle protein water partition coefficients (KMP/w) of 51 systematically selected organic anions and cations were determined experimentally. A comparison of the measured KMP/w with bovine serum albumin (BSA)-water partition coefficients showed that anionic chemicals sorb more strongly to BSA than to muscle protein (by up to 3.5 orders of magnitude), while cations sorb similarly to both proteins. Sorption isotherms of selected IOCs to muscle protein are linear (i.e., KMP/w is concentration independent), and KMP/w is only marginally influenced by pH value and salt concentration. Using the obtained data set of KMP/w a polyparameter linear free energy relationship (PP-LFER) model was established. The derived equation fits the data well (R(2) = 0.89, RMSE = 0.29). Finally, it was demonstrated that the in vitro measured KMP/w values of this study have the potential to be used to evaluate tissue-plasma partitioning of IOCs in vivo. PMID- 27265316 TI - Weak C-H acids as protonophores can carry hydrogen ions through lipid membranes and mitochondria: a case of o-carborane. AB - ortho-Carborane (1,2-C2B10H12) was found to be a carrier of protons in both mitochondrial and artificial lipid membranes, suggesting that this dicarborane can reversibly release hydrogen ions and diffuse through the membranes in neutral and anionic forms. Similar to conventional uncouplers (e.g. 2,4-dinitrophenol), o carborane stimulated mitochondrial respiration and decreased the membrane potential at concentrations of tens of micromoles. Protonophoric activity of o carborane was observed both by a fluorometric assay using pyranine-loaded liposomes and electrical current measurements across planar lipid bilayers. Substantial contribution of the proton flux to the o-carborane-mediated current was proved by a shift of the zero current voltage upon imposing a pH gradient across the membrane. Meta-carborane (1,7-C2B10H12) lacked the protonophoric activity in line with its reduced C-H acidity. The results suggest that weak C-H acids can exhibit protonophoric activity in the biological environment. The finding of a new class of protonophoric compounds is of substantial interest due to promising anti-obesity and anti-diabetic properties of uncouplers. PMID- 27265317 TI - Three-Dimensional Polydopamine Functionalized Coiled Microfibrous Scaffolds Enhance Human Mesenchymal Stem Cells Colonization and Mild Myofibroblastic Differentiation. AB - Electrospinning has been widely applied for tissue engineering due to its versatility of fabricating extracellular matrix (ECM) mimicking fibrillar scaffolds. Yet there are still challenges such as that these two-dimensional (2D) tightly packed, hydrophobic fibers often hinder cell infiltration and cell scaffold integration. In this study, polycaprolactone (PCL) was electrospun into a grounded coagulation bath collector, resulting in 3D coiled microfibers with in situ surface functionalization with hydrophilic, catecholic polydopamine (pDA). The 3D scaffolds showed biocompatibility and were well-integrated with human bone marrow derived human mesenchymal stem cells (hMSCs), with significantly higher cell penetration depth compared to that of the 2D PCL microfibers from traditional electrospinning. Further differentiation of human mesenchymal stem cells (hMSCs) into fibroblast phenotype in vitro indicates that, compared to the stiff, tightly packed, 2D scaffolds which aggravated myofibroblasts related activities, such as upregulated gene and protein expression of alpha-smooth muscle actin (alpha-SMA), 3D scaffolds induced milder myofibroblastic differentiation. The flexible 3D fibers further allowed contraction with the well integrated, mechanically active myofibroblasts, monitored under live-cell imaging, whereas the stiff 2D scaffolds restricted that. PMID- 27265318 TI - Modeling of Sustainable Base Production by Microbial Electrolysis Cell. AB - A predictive model for the microbial/electrochemical base formation from wastewater was established and compared to experimental conditions within a microbial electrolysis cell. A Na2 SO4 /K2 SO4 anolyte showed that model prediction matched experimental results. Using Shewanella oneidensis MR-1, a strong base (pH~13) was generated using applied voltages between 0.3 and 1.1 V. Due to the use of bicarbonate, the pH value in the anolyte remained unchanged, which is required to maintain microbial activity. PMID- 27265319 TI - Proteomic characterization of hempseed (Cannabis sativa L.). AB - This paper presents an investigation on hempseed proteome. The experimental approach, based on combinatorial peptide ligand libraries (CPLLs), SDS-PAGE separation, nLC-ESI-MS/MS identification, and database search, permitted identifying in total 181 expressed proteins. This very large number of identifications was achieved by searching in two databases: Cannabis sativa L. (56 gene products identified) and Arabidopsis thaliana (125 gene products identified). By performing a protein-protein association network analysis using the STRING software, it was possible to build the first interactomic map of all detected proteins, characterized by 137 nodes and 410 interactions. Finally, a Gene Ontology analysis of the identified species permitted to classify their molecular functions: the great majority is involved in the seed metabolic processes (41%), responses to stimulus (8%), and biological process (7%). BIOLOGICAL SIGNIFICANCE: Hempseed is an underexploited non-legume protein-rich seed. Although its protein is well known for its digestibility, essential amino acid composition, and useful techno-functional properties, a comprehensive proteome characterization is still lacking. The objective of this work was to fill this knowledge gap and provide information useful for a better exploitation of this seed in different food products. PMID- 27265320 TI - Proteomic changes occurring along gonad maturation in the edible sea urchin Paracentrotus lividus. AB - The reproductive stage of Paracentrotus lividus strongly influences product quality that, in turn, impacts significantly on the market price. Large, compact and sweet gonads are preferred, and sensory attributes are positively related to the ratio of nutritive phagocytes to gametes. Gonads at advanced maturation stages, although larger, have less desirable attributes, being more watery and bitter especially in females. Therefore, the best compromise among size, texture, and taste needs to be reached. In this study, wild P. lividus were collected along coastal Sardinia, and gonads in the recovery, pre-mature, mature, and spent stages were analyzed by gel-based and by shotgun proteomics. A detailed characterization of the proteome changes occurring in gonads of both sexes along maturation was achieved, and significant modifications were seen in numerous proteins involved in nutrient accumulation in nutritive phagocytes, as well as in gamete biology and maturation. Adding to an improved understanding of the P. lividus reproductive cycle in its natural environment, the results described in this work may form the basis for defining novel protein markers and procedures for an easier sexing and staging, and for monitoring sea urchin gonad maturation cycles in aquaculture plants. Mass spectrometry data are deposited in ProteomeXchange (PXD004200). SIGNIFICANCE: The sensory quality of P. lividus gonads is strongly influenced by the reproductive cycle, with significant changes in flavor, texture, and size. A better knowledge of the protein profiles, patterns, and markers associated with gonad sex and maturation stage can have useful implications for understanding and monitoring these changes. One of these is the ability to identify protein profiles specifically associated with a given stage and, in perspective, to identify maturation and sex markers. The comprehensive proteomic evaluation achieved in this work was made possible by the application of combined gel-based and shotgun approaches. As a result, this study generated the largest proteomic dataset available in the literature for P. lividus, as well as a general picture of protein abundance changes occurring along maturation. PMID- 27265321 TI - A proteomic analysis of Pakistan Daboia russelii russelii venom and assessment of potency of Indian polyvalent and monovalent antivenom. AB - To address the dearth of knowledge on the biochemical composition of Pakistan Russell's Viper (Daboia russelii russelii) venom (RVV), the venom proteome has been analyzed and several biochemical and pharmacological properties of the venom were investigated. SDS-PAGE (reduced) analysis indicated that proteins/peptides in the molecular mass range of ~56.0-105.0kDa, 31.6-51.0kDa, 15.6-30.0kDa, 9.0 14.2kDa and 5.6-7.2kDa contribute approximately 9.8%, 12.1%, 13.4%, 34.1% and 30.5%, respectively of Pakistan RVV. Proteomics analysis of gel-filtration peaks of RVV resulted in identification of 75 proteins/peptides which belong to 14 distinct snake venom protein families. Phospholipases A2 (32.8%), Kunitz type serine protease inhibitors (28.4%), and snake venom metalloproteases (21.8%) comprised the majority of Pakistan RVV proteins, while 11 additional families accounted for 6.5-0.2%. Occurrence of aminotransferase, endo-beta-glycosidase, and disintegrins is reported for the first time in RVV. Several of RVV proteins/peptides share significant sequence homology across Viperidae subfamilies. Pakistan RVV was well recognized by both the polyvalent (PAV) and monovalent (MAV) antivenom manufactured in India; nonetheless, immunological cross-reactivity determined by ELISA and neutralization of pro coagulant/anticoagulant activity of RVV and its fractions by MAV surpassed that of PAV. BIOLOGICAL SIGNIFICANCE: The study establishes the proteome profile of the Pakistan RVV, thereby indicating the presence of diverse proteins and peptides that play a significant role in the pathophysiology of RVV bite. Further, the proteomic findings will contribute to understand the variation in venom composition owing to different geographical location and identification of pharmacologically important proteins in Pakistan RVV. PMID- 27265322 TI - It's all about functionality: How can metaproteomics help us to discuss the attributes of ecological relevance in soil? AB - Soil metaproteomics has been recently developed in order to link the phylogeny and functionality of soil microorganisms. After the development of protein extraction and peptide analysis, the use of improved mass-spectrometric systems has allowed the description of the microbial composition and the identification of proteins in soils subjected to deforestation, restoration, contamination and different agricultural managements. In this letter, we encourage one step-forward for soil metaproteomics. We believe that proteomics can complement ecological attributes that control the dynamics of soil microbial populations. Among these attributes, we highlight the resistance, resilience and plasticity of microbial populations. Providing with functional basis to these attributes will extend our knowledge on the microbial-mediated mechanisms regulating the impacts of climate change and agricultural management in the near future. PMID- 27265323 TI - A linkage map for the Newt Notophthalmus viridescens: Insights in vertebrate genome and chromosome evolution. AB - Genetic linkage maps are fundamental resources that enable diverse genetic and genomic approaches, including quantitative trait locus (QTL) analyses and comparative studies of genome evolution. It is straightforward to build linkage maps for species that are amenable to laboratory culture and genetic crossing designs, and that have relatively small genomes and few chromosomes. It is more difficult to generate linkage maps for species that do not meet these criteria. Here, we introduce a method to rapidly build linkage maps for salamanders, which are known for their enormous genome sizes. As proof of principle, we developed a linkage map with thousands of molecular markers (N=2349) for the Eastern newt (Notophthalmus viridescens). The map contains 12 linkage groups (152.3-934.7cM), only one more than the number of chromosome pairs. Importantly, this map was generated using RNA isolated from a single wild caught female and her 28 offspring. We used the map to reveal chromosome-scale conservation of synteny among N. viridescens, A. mexicanum (Urodela), and chicken (Amniota), and to identify large conserved segments between N. viridescens and Xenopus tropicalis (Anura). We also show that met1, a major effect QTL that regulates the expression of alternate metamorphic and paedomorphic modes of development in Ambystoma, associates with a chromosomal fusion that is not found in the N. viridescens map. Our results shed new light on the ancestral amphibian karyotype and reveal specific fusion and translocation events that shaped the genomes of three amphibian model taxa. The ability to rapidly build linkage maps for large salamander genomes will enable genetic and genomic analyses within this important vertebrate group, and more generally, empower comparative studies of vertebrate biology and evolution. PMID- 27265325 TI - Zika virus transmission: What should we be concerned about apart from mosquito control. PMID- 27265324 TI - Imprinted survival genes preclude loss of heterozygosity of chromosome 7 in cancer cells. AB - The genomes of a wide range of cancers, including colon, breast, and thyroid cancers, frequently show copy number gains of chromosome 7 and rarely show loss of heterozygosity. The molecular basis for this phenomenon is unknown. Strikingly, oncocytic follicular thyroid carcinomas can display an extreme genomic profile, with homozygosity of all chromosomes except for chromosome 7. The observation that homozygosity of chromosome 7 is never observed suggests that retention of heterozygosity is essential for cells. We hypothesized that cell survival genes are genetically imprinted on either of two copies of chromosome 7, which thwarts loss of heterozygosity at this chromosome in cancer cells. By employing a DNA methylation screen and gene expression analysis, we identified six imprinted genes that force retention of heterozygosity on chromosome 7. Subsequent knockdown of gene expression showed that CALCR, COPG2, GRB10, KLF14, MEST, and PEG10 were essential for cancer cell survival, resulting in reduced cell proliferation, G1 -phase arrest, and increased apoptosis. We propose that imprinted cell survival genes provide a genetic basis for retention of chromosome 7 heterozygosity in cancer cells. The monoallelically expressed cell survival genes identified in this study, and the cellular pathways that they are involved in, offer new therapeutic targets for the treatment of tumours showing retention of heterozygosity on chromosome 7. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27265326 TI - A Red to Near-IR Fluorogen: Aggregation-Induced Emission, Large Stokes Shift, High Solid Efficiency and Application in Cell-Imaging. AB - A tetraphenylethene (TPE) derivative modified with the strong electron acceptor 2 dicyano-methylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) was obtained in high yield by a simple two-step reaction. The resultant TPE-TCF showed evident aggregation-induced emission (AIE) features and pronounced solvatochromic behavior. Changing the solvent from apolar cyclohexane to highly polar acetonitrile, the emission peak shifted from 560 to 680 nm (120 nm redshift). In an acetonitrile solution and in the solid powder, the Stokes shifts are as large as 230 and 190 nm, respectively. The solid film emits red to near-IR (red-NIR) fluorescence with an emission peak at 670 nm and a quantum efficiency of 24.8 %. Taking the advantages of red-NIR emission and high efficiency, nanoparticles (NPs) of TPE-TCF were fabricated by using tat-modified 1,2-distearoylsn-glycero-3 phosphor-ethanol-amine-N-[methoxy-(polyethyl-eneglycol)-2000] as the encapsulation matrix. The obtained NPs showed perfect membrane penetrability and high fluorescent imaging quality of cell cytoplasm. Upon co-incubation with 4,6 diamidino-2-phenylindole (DAPI) in the presence of tritons, the capsulated TPE TCF nanoparticles could enter into the nucleus and displayed similar staining properties to those of DAPI. PMID- 27265327 TI - Methane adsorption and dissociation on iron oxide oxygen carriers: the role of oxygen vacancies. AB - We performed ab initio DFT+U calculations to explore the interaction between methane and iron oxide oxygen carriers for chemical looping reaction systems. The adsorption of CH4 and CHx (x = 0-3) radicals on alpha-Fe2O3(001), and the influence of oxygen vacancies at the top surface and on the subsurface on the adsorption properties of the radicals was investigated. The adsorption strength for CH4 and C radicals at the top of the alpha-Fe2O3(001) surface in the presence of oxygen vacancies is lower than that on the stoichiometric surface. However, for methyl (CH3), methylene (CH2) and methine (CH) radicals, it is correspondingly higher. In contrast, the oxygen vacancy formation on the subsurface not only increases the adsorption strength of CH3, CH2 and CH radicals, but also facilitates C radical adsorption. We found that oxygen vacancies significantly affect the adsorption configuration of CHx radicals, and determine the probability of finding an adsorbed species in the stoichiometric region and the defective region at the surface. With the obtained adsorption geometries and energetics of these species adsorbed on the surface, we extend the analysis to CH4 dissociation under chemical looping reforming conditions. The distribution of adsorbed CH4 and CHx (x = 0-3) radicals is calculated and analyzed which reveals the relationship between adsorbed CHx radical configuration and oxygen vacancies in iron oxide. Also, the oxygen vacancies can significantly facilitate CH4 activation by lowering the dissociation barriers of CH3, CH2 and CH radicals. However, when the oxygen vacancy concentration reaches 2.67%, increasing the oxygen vacancy concentration cannot continue to lower the CH dissociation barrier. The study provides fundamental insights into the mechanism of CH4 dissociation on iron based oxygen carriers and also provide guidance to design more efficient oxygen carriers. PMID- 27265329 TI - Therapeutic Plasma Exchange and the Clinical Applications. PMID- 27265330 TI - An Education Programme on Sickle Cell Anemia and beta-Thalassemia for the 8th Grade Students. AB - beta-thalassemia and sickle cell anemia (SCA) are major health problems in Cukurova. Screening studies have been carried on in this region for many years. The government started premarital screening programme and prenatal diagnosis has been done in Cukurova University Medical Faculty since 1992. In spite of all these, the prevention programme has not been successful. The purpose of this study was to start an education programme to increase the awareness of the people for these severe hereditary diseases. The target population was the 8th grade students. A visual presentation was given to students on Thalassemia and SCA after examining the curriculum in the Biology and/or the Science books. A total of 1221 students in seven Elementary Schools were informed. A questionnaire was given to five schools before the presentation and to two after the presentation. The comparison of the two group's result showed that the information given was well received. Thus, an extensive education programme encompassing doctors, health personel, civil and religious leaders and the support of the government will result in nil SCA and Thalassemia births. PMID- 27265331 TI - Refractory Thrombocytopenia with Multilineage Dysplasia: A Rare Type of Myelodysplastic Syndrome. AB - Thrombocytopenia may be the presenting cytopenia of myelodysplastic syndrome (MDS) and is named as refractory thrombocytopenia (RT) and categorized in the refractory cytopenia with multilineage dysplasia (RCMD) group according to the recent World Health Organization (WHO) classification of the acute leukemias and MDS. Abnormal cytogenetics can be found in 60% to 80% of patients with MDS. Most common cytogenetic abnormalities include monosomy 5, 5q-, monosomy 7, trisomy 8, deletion 20q and loss of X or Y chromosome. Here we report clinical features and outcomes of nine patients with RT. Cytogenetic abnormalities were detected in seven. Among two patients who have a normal karyotype at diagnosis, one of them transformed to acute myeloid leukemia (AML). During a median follow-up of 29 months, two patients died of hemorrhagia and one of AML. The features and prognosis of patients with RT needs to be determined by larger series. PMID- 27265328 TI - Defining the identity of mouse embryonic dermal fibroblasts. AB - Embryonic dermal fibroblasts in the skin have the exceptional ability to initiate hair follicle morphogenesis and contribute to scarless wound healing. Activation of the Wnt signaling pathway is critical for dermal fibroblast fate selection and hair follicle induction. In humans, mutations in Wnt pathway components and target genes lead to congenital focal dermal hypoplasias with diminished hair. The gene expression signature of embryonic dermal fibroblasts during differentiation and its dependence on Wnt signaling is unknown. Here we applied Shannon entropy analysis to identify the gene expression signature of mouse embryonic dermal fibroblasts. We used available human DNase-seq and histone modification ChiP-seq data on various cell-types to demonstrate that genes in the fibroblast cell identity signature can be epigenetically repressed in other cell types. We found a subset of the signature genes whose expression is dependent on Wnt/beta-catenin activity in vivo. With our approach, we have defined and validated a statistically derived gene expression signature that may mediate dermal fibroblast identity and function in development and disease. genesis 54:415-430, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27265332 TI - Coexistence of Two Prothrombotic Mutations, Factor V 1691 G-A and Prothrombin 20210 G-A, and the Risk of Thrombosis in Turkish Population. AB - This report summarizes the coexistence of two mutations; Factor V 1691 G-A and prothrombin 20210 G-A in Turkish population and emphasises on the point that, this coexistence increases the risk of thrombosis in such patients. In thrombophilia screening programs, these two variants should be included, particularly in Turkish population. PMID- 27265333 TI - Effect of alpha-Tocopherol on Lipid Peroxidation Caused by Cisplatin in Rat Kidney. AB - Cisplatin (CDDP) is one of the most commonly used antineoplastic agents in current clinical practice. The major toxicities of CDDP are nonhaematological as nephrotoxicity and ototoxicity. Free oxygen radicals are known to play major role in CDDP-induced acute renal failure in rats. alpha-tocopherol is one of the well known antioxidant agents. This study was designed to investigate the role of alpha-tocopherol pretreatment against CDDP-induced lipid peroxidation in rat kidney. Male Wistar rats were divided into three groups and treated as follows: control (saline intraperitoneally), CDDP (10 kg/kg, intraperitoneally), alpha tocopherol (200 kg/kg, plus CDDP, intraperitoneally). Rats were sacrificed on third day of the treatment, and kidney tissues were obtained and analyzed. CDDP treated rats showed high malondialdehyde (MDA) levels (p< 0.05). In the CDDP plus alpha-tocopherol group, renal MDA levels were not significantly different from the controls. These data suggest that alpha-tocopherol may be used to prevent CDDP-induced lipid peroxidation. PMID- 27265334 TI - Acute Monoblastic Leukemia as a Second Malignancy After Doxorubicin and Cisplatin Treatment for Osteosarcoma. AB - Secondary or therapy-related acute myeloid leukemia (t-AML) occurs as a complication of various chemotherapy regimens. In pediatric age group, leukemia as a second malignancy after osteosarcoma treatment with doxorubicin and cisplatin is relatively rare. A 15-year-old girl was admitted to our hospital with signs and symptoms of leukemia. She had been treated one-year earlier with doxorubicin and cisplatin for osteosarcoma of the left femur. The patient was diagnosed with acute monoblastic leukemia on the basis of bone marrow examination and immunophenotype analysis. There were no cytogenetic abnormalities. The patient's father had been diagnosed with pelvic chondrosarcoma, which suggested a familial susceptibility to cancer. We interpreted this as a rare case of t- AML with normal cytogenetic analysis, and believe the disease was induced by the addition of platinum compounds to a regimen including topoisomerase II inhibitors. PMID- 27265335 TI - A Case of Brucellosis Presenting with Severe Thrombocytopenia. AB - Thrombocytopenia is one of the rare hematologic complication of brucellosis. Herein a case of brucellosis with severe thrombocytopenia was reported. The patient was admitted to hematology service with epistaxis, ecchymoses, fever, thrombocytopenia (0.6 x 103/MUL) and anemia. His initial diagnosis was idiopathic thrombocytopenic purpura. Corticosteroid treatment was started and erythrocyte and platelet suspensions were transfused. Despite this treatment clinical symptoms and laboratory disorders were not improved. No significant pathology was detected in the examination of bone marrow aspiration. On the seventh day, Brucella abortus was yielded from his blood cultures. Steroid was stopped and rifampicin plus doxycycline started. His clinical symptoms were disappeared and laboratory findings improved (thrombocyte count: 205 x 103/MUL) at the second week of the antibiotic treatment. This case was interesting showing us that thrombocyte count might decrease to very low levels in brucellosis. So that, especially in the endemic areas, brucellosis should be kept in mind for the etiology of fever and thrombocytopenia. PMID- 27265336 TI - Iatrogenic Kaposi 's Sarcoma. AB - The development of Kaposi's sarcoma (KS) has been associated with either iatrogenic or underlying disease related immunodeficiency. We report a case with iatrogenic Kaposi's sarcoma developed after treatment of non- Hodgkin's lymphoma (NHL) who was achieved partial clinical remission with systemic chemotherapy. PMID- 27265337 TI - Images in Hematology. PMID- 27265338 TI - Infantile Malignant Osteopetrosis: Delay in Diagnosis Eliminates Chance of Cure. PMID- 27265339 TI - High Factor VIII Antigen Levels are not Associated with Factor VIII Gene Polymorphisms. PMID- 27265340 TI - Dynamics of inert spheres in active suspensions of micro-rotors. AB - Inert particles suspended in active fluids of self-propelled particles are known to often exhibit enhanced diffusion and novel coherent structures. Here we numerically investigate the dynamical behavior and self-organization in a system consisting of passive and actively rotating spheres of the same size. The particles interact through direct collisions and the fluid flows generated as they move. In the absence of passive particles, three states emerge in a binary mixture of spinning spheres depending on particle fraction: a dilute gas-like state where the rotors move chaotically, a phase-separated state where like rotors move in lanes or vortices, and a jammed state where crystals continuously assemble, melt and move (K. Yeo, E. Lushi, and P. M. Vlahovska, Phys. Rev. Lett., 2015, 114, 188301). Passive particles added to the rotor suspension modify the system dynamics and pattern formation: while states identified in the pure active suspension still emerge, they occur at different densities and mixture proportions. The dynamical behavior of the inert particles is also non-trivially dependent on the system composition. PMID- 27265341 TI - Dispersal of invasive Phytolacca americana seeds by birds in an urban garden in China. AB - Although seed dispersal is a key process determining the regeneration and spread of invasive plant populations, few studies have explicitly addressed the link between dispersal vector behavior and seedling recruitment to gain insight into the invasion process within an urban garden context. We evaluated the role of bird vectors in the dispersal of pokeweed (Phytolacca americana), a North American herb that is invasive in urban gardens in China. Fruiting P. americana attracted both generalist and specialist bird species that fed on and dispersed its seeds. The generalist species Pycnonotus sinensis and Urocissa erythrorhyncha were the most frequent dispersers. Seedling numbers of P. americana were strongly associated with the perching behavior of frugivorous birds. If newly recruited bird species use seedling-safe perching sites, the P. americana will regenerate faster, which would enhance its invasive potential. Based on our observations, we conclude that the 2 main bird vectors, P. sinensis and U. erythrorhyncha, provide potential effective dispersal agents for P. americana. Our results highlight the role of native birds in seed dispersal of invasive plants in urban gardens. PMID- 27265342 TI - Temporal Variabilities in Genetic Patterns and Antibiotic Resistance Profiles of Enterococci Isolated from Human Feces. AB - Temporal variabilities in the genetic patterns and antibiotic resistance profiles of enterococci were monitored over a 7-month period. Enterococcus faecalis isolates (103 strains) collected from feces showed only one genetic pattern and antibiotic resistance profile within 0 d and 30 d. In contrast, after 60 d and 90 d, the genetic patterns and antibiotic resistance profiles of all E. faecalis isolates (8 strains) clearly differed within 30 d. These results indicate that the genetic patterns and antibiotic resistance profiles of E. faecalis in human feces changed to completely dissimilar patterns between 1 and 2 months. PMID- 27265343 TI - Cladophialophora inabaensis sp. nov., a New Species among the Dark Septate Endophytes from a Secondary Forest in Tottori, Japan. AB - A novel species of Cladophialophora is herein described from the natural environment of secondary forest soil in Japan, which was able to be colonized by the host plant root. Morphological observations indicated that the isolate is distinct from previously identified species, and, thus, is described as the new species, C. inabaensis sp. nov. PMID- 27265344 TI - Phylogenetically Diverse Burkholderia Associated with Midgut Crypts of Spurge Bugs, Dicranocephalus spp. (Heteroptera: Stenocephalidae). AB - Diverse phytophagous heteropteran insects, commonly known as stinkbugs, are associated with specific gut symbiotic bacteria, which have been found in midgut cryptic spaces. Recent studies have revealed that members of the stinkbug families Coreidae and Alydidae of the superfamily Coreoidea are consistently associated with a specific group of the betaproteobacterial genus Burkholderia, called the "stinkbug-associated beneficial and environmental (SBE)" group, and horizontally acquire specific symbionts from the environment every generation. However, the symbiotic system of another coreoid family, Stenocephalidae remains undetermined. We herein investigated four species of the stenocephalid genus Dicranocephalus. Examinations via fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM) revealed the typical arrangement and ultrastructures of midgut crypts and gut symbionts. Cloning and molecular phylogenetic analyses of bacterial genes showed that the midgut crypts of all species are colonized by Burkholderia strains, which were further assigned to different subgroups of the genus Burkholderia. In addition to the SBE-group Burkholderia, a number of stenocephalid symbionts belonged to a novel clade containing B. sordidicola and B. udeis, suggesting a specific symbiont clade for the Stenocephalidae. The symbiotic systems of stenocephalid bugs may provide a unique opportunity to study the ongoing evolution of symbiont associations in the stinkbug-Burkholderia interaction. PMID- 27265345 TI - Physical Activity and Gastric Residuals as Biomarkers for Region-Specific NEC Lesions in Preterm Neonates. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is a serious feeding-related inflammatory gut disease with high mortality. Early clinical markers of NEC are of great importance for optimizing preventive interventions. OBJECTIVE: Using preterm pigs as models, we hypothesized that an early postnatal onset of NEC can be predicted by decreased physical activity during the first few days after birth. METHODS: Cesarean-delivered preterm pigs were fed parenteral nutrition and increasing amounts of formula for 5 days after birth (n = 120). Their physical activity was quantified by a continuous camera surveillance system and they were evaluated twice daily for clinical signs of apathy, discoloration, respiratory distress, abdominal distension and diarrhea. The volume of gastric residuals and the presence of macroscopic NEC-like lesions in the stomach, intestine and colon were recorded at euthanasia on day 5. RESULTS: Half of the pigs (48%) showed clear NEC-like lesions on day 5, and these individuals had more adverse clinical symptoms from day 3 but decreased physical activity already from day 2 relative to the unaffected pigs (both p < 0.05). Only animals with NEC lesions in the small intestine had lower physical activity on days 2 and 3, and the increased volume of gastric residuals was specifically related to colon lesions (both p < 0.05). CONCLUSIONS: Decreased physical activity precedes the clinical symptoms of NEC in the small intestine of preterm pigs, and increased gastric residuals predict NEC lesions in the colon. Physical activity and gastric residuals may function as clinical biomarkers for region-specific NEC lesions in preterm neonates. PMID- 27265346 TI - Acute bacterial meningitis in adults. AB - Over the past several decades, the incidence of bacterial meningitis in children has decreased but there remains a significant burden of disease in adults, with a mortality of up to 30%. Although the pathogenesis of bacterial meningitis is not completely understood, knowledge of bacterial invasion and entry into the CNS is improving. Clinical features alone cannot determine whether meningitis is present and analysis of cerebrospinal fluid is essential for diagnosis. Newer technologies, such as multiplex PCR, and novel diagnostic platforms that incorporate proteomics and genetic sequencing, might help provide a quicker and more accurate diagnosis. Even with appropriate antimicrobial therapy, mortality is high and so attention has focused on adjunctive therapies; adjunctive corticosteroids are beneficial in certain circumstances. Any further improvements in outcome are likely to come from either modulation of the host response or novel approaches to therapy, rather than new antibiotics. Ultimately, the best hope to reduce the disease burden is with broadly protective vaccines. PMID- 27265348 TI - Raising the bar for the adjuvant treatment of pancreatic cancer. PMID- 27265347 TI - Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). AB - BACKGROUND: Although adjuvant chemotherapy with gemcitabine is standard care for resected pancreatic cancer, S-1 has shown non-inferiority to gemcitabine for advanced disease. We aimed to investigate the non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for pancreatic cancer in terms of overall survival. METHODS: We did a randomised, open-label, multicentre, non-inferiority phase 3 trial undertaken at 33 hospitals in Japan. Patients who had histologically proven invasive ductal carcinoma of the pancreas, pathologically documented stage I-III, and no local residual or microscopic residual tumour, and were aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive gemcitabine (1000 mg/m(2), intravenously administered on days 1, 8, and 15, every 4 weeks [one cycle], for up to six cycles) or S-1 (40 mg, 50 mg, or 60 mg according to body surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles) at the data centre by a modified minimisation method, balancing residual tumour status, nodal status, and institutions. The primary outcome was overall survival in the two treatment groups, assessed in the per-protocol population, excluding ineligible patients and those not receiving the allocated treatment. The protocol prespecified that the superiority of S-1 with respect to overall survival was also to be assessed in the per-protocol population by a log-rank test, if the non-inferiority of S-1 was verified. We estimated overall and relapse-free survival using the Kaplan Meier methods, and assessed non-inferiority of S-1 to gemcitabine using the Cox proportional hazard model. The expected hazard ratio (HR) for mortality was 0.87 with a non-inferiority margin of 1.25 (power 80%; one-sided type I error 2.5%). This trial is registered at UMIN CTR (UMIN000000655). FINDINGS: 385 patients were randomly assigned to treatment between April 11, 2007, and June 29, 2010 (193 to the gemcitabine group and 192 to the S-1 group). Of these, three were exlcuded because of ineligibility and five did not receive chemotherapy. The per-protocol population therefore consisted of 190 patients in the gemcitabine group and 187 patients in the S-1 group. On Sept 15, 2012, following the recommendation from the independent data and safety monitoring committee, this study was discontinued because the prespecified criteria for early discontinuation were met at the interim analysis for efficacy, when all the protocol treatments had been finished. Analysis with the follow-up data on Jan 15, 2016, showed HR of mortality was 0.57 (95% CI 0.44-0.72, pnon-inferiority<0.0001, p<0.0001 for superiority), associated with 5-year overall survival of 24.4% (18.6-30.8) in the gemcitabine group and 44.1% (36.9-51.1) in the S-1 group. Grade 3 or 4 leucopenia, neutropenia, aspartate aminotransferase, and alanine aminotransferase were observed more frequently in the gemcitabine group, whereas stomatitis and diarrhoea were more frequently experienced in the S-1 group. INTERPRETATION: Adjuvant chemotherapy with S-1 can be a new standard care for resected pancreatic cancer in Japanese patients. These results should be assessed in non-Asian patients. FUNDING: Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical. PMID- 27265349 TI - No relevant midbrain atrophy in Parkinson's disease. AB - AIMS OF THE STUDY: To investigate whether significant midbrain atrophy is present in Parkinson's disease (PD), and if so, whether it can be used as a marker of striatal dopaminergic degeneration. METHODS: In total, 150 PD patients and 155 controls were scanned with both brain dopamine transporter (DAT) [123 I]FP-CIT SPECT and 1.5T MRI. Midbrain atrophy was measured from sagittal MRIs using the midbrain-to-pons ratios. Both striatal region-of-interest-based (Brass) and striatal and extrastriatal voxel-by-voxel-based DAT binding (SPM8) were investigated in relation to midbrain atrophy. RESULTS: The midbrain-to-pons ratios in PD patients were slightly lower than those in the controls (mean 0.59 vs 0.61, P < 0.05). The ratios did not significantly correlate with striatal or extrastriatal [123 I]FP-CIT uptake in controls or patients with PD. CONCLUSIONS: Mild midbrain atrophy is present in PD and can be detected with MRI. However, the midbrain atrophy in PD is not associated with the level of striatal dopaminergic dysfunction, and midbrain measurements therefore cannot be used as a clinically useful predictor of dopamine function. PMID- 27265350 TI - Preparation of large size, few-layer black phosphorus nanosheets via phytic acid assisted liquid exfoliation. AB - Ultrathin uniform BP nanosheets with lateral dimensions of up to several tens of micrometers were prepared via a small molecule-assisted liquid phase exfoliation method, which exhibited attractive electron accepting abilities from photosensitizers and was thus promising in diverse applications such as photocatalysis and photovoltaics. PMID- 27265351 TI - The Trans-Pacific Partnership Agreement and health: few gains, some losses, many risks. AB - BACKGROUND: In early October 2015, 12 nations signed the Trans-Pacific Partnership Agreement (TPPA), promoted as a model '21(st) century' trade and investment agreement that other countries would eventually join. There are growing concerns amongst the public health community about the potential health implications of such WTO+ trade and investment agreements, but little existing knowledge on their potential health impacts. METHODS AND RESULTS: We conducted a health impact review which allows for a summary estimation of the most significant health impacts of a set of policies, in our case the TPPA. Our analysis shows that there are a number of potentially serious health risks, with the following key pathways linking trade to health: access to medicines, reduced regulatory space, investor-state dispute settlement (ISDS), and environmental protection and labor rights. We also note that economic gains that could translate into health benefits will likely be inequitably distributed. CONCLUSION: Our analysis demonstrates the need for the public health community to be knowledgeable about trade issues and more engaged in trade negotiations. In the context of the COP21 climate change Agreement, and the UN Sustainable Development Goals, this may be an opportune time for TPPA countries to reject it as drafted, and rethink what should be the purpose of such agreements in light of (still) escalating global wealth inequalities and fragile environmental resources the two most foundational elements to global health equity. PMID- 27265352 TI - Bacillus oryzisoli sp. nov., isolated from rice rhizosphere. AB - The taxonomy of strain 1DS3-10T, a Gram-staining-positive, endospore-forming bacterium isolated from rice rhizosphere, was investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that the novel strain was grouped with established members of the genus Bacillus and appeared to be closely related to the type strains Bacillus benzoevorans DSM 5391T (97.9 %), Bacillus circulans DSM 11T (97.7 %), Bacillus novalis JCM 21709T (97.3 %), Bacillus soli JCM 21710T (97.3 %), Bacillus oceanisediminis CGMCC 1.10115T (97.3 %) and BacillusnealsoniiFO-92T (97.1 %). The fatty acid profile of strain 1DS3-10T, which showed a predominance of iso-C15 : 0 and anteiso-C15 : 0, supported the allocation of the strain to the genus Bacillus. The predominant menaquinone was MK-7 (100 %). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and unknown aminolipids. Cell-wall peptidoglycan contained meso-diaminopimelic acid. DNA-DNA hybridization values between strain 1DS3-10T and the type strains of closely related species were 25 33 %, which supported that 1DS3-10T represented a novel species in the genus Bacillus. The results of some physiological and biochemical tests also allowed the phenotypic differentiation of strain 1DS3-10T from the most closely related recognized species. On the basis of the phylogenetic and phenotypic evidence, strain 1DS3-10T represents a novel species of the genus Bacillus, for which the name Bacillus oryzisoli sp. nov. is proposed. The type strain of the novel species is 1DS3-10T (=ACCC 19781T=DSM 29761T). PMID- 27265354 TI - Spectrofluorimetric Determination of Beryllium by Mean Centering of Ratio Spectra. AB - Trace amounts of beryllium has been determined by spectrofluorimetric method that used morin as fluorimetric reagent. Beryllium gives a highly fluorescent complex with morin. The excitation wavelength of morin and Be-morin complex were 410 and 430. The fluorescence spectra of morin and Be-morin complex were overlaped in excitation wavelength of 430 nm. A method based on mean centering of ratio spectra has been performed to remove the interference caused by morin as it overlaps with the Be-morin spectra. The linear range of beryllium concentration is in 0.2-200 ppb range. The parameters of detection limit and RSD were 0.18 ppb and 4.6 % respectively. This method was used for determination of beryllium in copper-beryllium alloy as a real sample. In determination of Be(II), the interference by Cu(II) was very serious, which was eliminated by adding triethanolamine. PMID- 27265353 TI - Daily co-trimoxazole prophylaxis to prevent mortality in children with complicated severe acute malnutrition: a multicentre, double-blind, randomised placebo-controlled trial. AB - BACKGROUND: Children with complicated severe acute malnutrition (SAM) have a greatly increased risk of mortality from infections while in hospital and after discharge. In HIV-infected children, mortality and admission to hospital are prevented by daily co-trimoxazole prophylaxis, despite locally reported bacterial resistance to co-trimoxazole. We aimed to assess the efficacy of daily co trimoxazole prophylaxis on survival in children without HIV being treated for complicated SAM. METHODS: We did a multicentre, double-blind, randomised, placebo controlled study in four hospitals in Kenya (two rural hospitals in Kilifi and Malindi, and two urban hospitals in Mombasa and Nairobi) with children aged 60 days to 59 months without HIV admitted to hospital and diagnosed with SAM. We randomly assigned eligible participants (1:1) to 6 months of either daily oral co trimoxazole prophylaxis (given as water-dispersible tablets; 120 mg per day for age <6 months, 240 mg per day for age 6 months to 5 years) or matching placebo. Assignment was done with computer-generated randomisation in permuted blocks of 20, stratified by centre and age younger or older than 6 months. Treatment allocation was concealed in opaque, sealed envelopes and patients, their families, and all trial staff were masked to treatment assignment. Children were given recommended medical care and feeding, and followed up for 12 months. The primary endpoint was mortality, assessed each month for the first 6 months, then every 2 months for the second 6 months. Secondary endpoints were nutritional recovery, readmission to hospital, and illness episodes treated as an outpatient. Analysis was by intention to treat. This trial was registered at ClinicalTrials.gov, number NCT00934492. FINDINGS: Between Nov 20, 2009, and March 14, 2013, we recruited and assigned 1778 eligible children to treatment (887 to co-trimoxazole prophylaxis and 891 to placebo). Median age was 11 months (IQR 7 16 months), 306 (17%) were younger than 6 months, 300 (17%) had oedematous malnutrition (kwashiorkor), and 1221 (69%) were stunted (length-for-age Z score < 2). During 1527 child-years of observation, 122 (14%) of 887 children in the co trimoxazole group died, compared with 135 (15%) of 891 in the placebo group (unadjusted hazard ratio [HR] 0.90, 95% CI 0.71-1.16, p=0.429; 16.0 vs 17.7 events per 100 child-years observed (CYO); difference -1.7 events per 100 CYO, 95% CI -5.8 to 2.4]). In the first 6 months of the study (while participants received study medication), 63 suspected grade 3 or 4 associated adverse events were recorded among 57 (3%) children; 31 (2%) in the co-trimoxazole group and 32 (2%) in the placebo group (incidence rate ratio 0.98, 95% CI 0.58-1.65). The most common adverse events of these grades were urticarial rash (grade 3, equally common in both groups), neutropenia (grade 4, more common in the co-trimoxazole group), and anaemia (both grades equally common in both groups). One child in the placebo group had fatal toxic epidermal necrolysis with concurrent Pseudomonas aeruginosa bacteraemia. INTERPRETATION: Daily co-trimoxazole prophylaxis did not reduce mortality in children with complicated SAM without HIV. Other strategies need to be tested in clinical trials to reduce deaths in this population. FUNDING: Wellcome Trust, UK. PMID- 27265355 TI - Effect of Adjuvant Chemotherapy on Stage II Rectal Cancer Outcomes After Preoperative Short-Course Radiotherapy. AB - BACKGROUND: Adjuvant chemotherapy (AC) is offered to patients with stage II rectal cancer, but its use is controversial. We examined population-based outcomes of patients with pathologic stage II rectal cancer treated with AC after preoperative short-course radiotherapy. MATERIALS AND METHODS: We included patients diagnosed with pathologic stage II tumors from 1999 to 2009 in British Columbia. The disease-specific survival (DSS), relapse-free (RFS), and overall survival (OS) were assessed. Multivariate models adjusting for age, gender, Eastern Cooperative Oncology Group, and high-risk features (ie, pT4, poor differentiation, < 12 lymph nodes removed, lymphovascular invasion, perineural invasion, or obstruction or perforation) were constructed. RESULTS: Of 851 patients reviewed, 330 had received preoperative short-course radiotherapy, of whom 123 (37%) subsequently received AC. Patients treated with AC were younger (median age 61 vs. 73 years; P < .0001), reported better Eastern Cooperative Oncology Group status (P < .0001), and had more high-risk features (P < .0001). On univariate analysis, AC was associated with improved DSS (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.36-0.94; P = .028), RFS (HR, 0.62; 95% CI, 0.39-0.98; P = .043), and OS (HR, 0.42; 95% CI, 0.30-0.59; P < .0001). On multivariate analysis, these outcomes were not significant (DSS HR, 0.83; 95% CI, 0.43-1.61; P = .58; RFS HR, 0.82; 95% CI, 0.44-1.50; P = .51; OS HR, 0.62; 95% CI, 0.37-1.03; P = .064). Subgroup analysis suggested AC improved DSS (HR, 0.25; 95% CI, 0.07-0.89; P = .033), RFS (HR, 0.24; 95% CI, 0.07-0.85; P = .027), and OS (HR, 0.22; 95% CI, 0.069-0.70; P = .011) only in patients with >= 2-high risk features. CONCLUSION: In the present population-based cohort of patients with stage II rectal cancer, AC did not improve the outcomes in unselected patients. In a small subgroup of patients with >= 2 risk factors, we noted improved outcomes with AC use. PMID- 27265356 TI - Stress fractures of the femoral neck in runners: a review. AB - A systematic review, following strict inclusion criteria, identified 32/48 low and 16/48 high-performance runners with stress fractures of the femoral neck. Surgical treatment was performed in 33/48 cases and was significantly higher (p = 0.009) in high-performance runners. Among the 28/48 runners who resumed running, there were significantly more lower-performance runners (23/32) than higher performing runners (5/16) (p = 0.012) and significantly more non-displaced (22/30) than displaced fractures (6/18) (p = 0.014). Complicated cases showed significantly less favourable follow-up results (p = 0.036). A significantly shorter (p = 0.032) diagnostic time for evaluation occurred with a previous history of a stress fracture or a relevant comorbidity. Stress fractures of the femoral neck represent an incisive incident for runners, and early consideration in the differential diagnosis of hip pain is required to avoid potential long term sequelae and suboptimal function. PMID- 27265357 TI - Genetic variations and miRNA-target interactions contribute to natural phenotypic variations in Populus. AB - Variation in regulatory factors, including microRNAs (miRNAs), contributes to variation in quantitative and complex traits. However, in plants, variants in miRNAs and their target genes that contribute to natural phenotypic variation, and the underlying regulatory networks, remain poorly characterized. We investigated the associations and interactions of single-nucleotide polymorphisms (SNPs) in miRNAs and their target genes with phenotypes in 435 individuals from a natural population of Populus. We used RNA-seq to identify 217 miRNAs differentially expressed in a tension wood system, and identified 1196 candidate target genes; degradome sequencing confirmed 60 of the target sites. In addition, 72 miRNA-target pairs showed significant co-expression. Gene ontology (GO) term analysis showed that most of the genes in the co-regulated pairs participate in biological regulation. Genome resequencing found 5383 common SNPs (frequency >= 0.05) in 139 miRNAs and 31 037 SNPs in 819 target genes. Single-SNP association analyses identified 232 significant associations between wood traits (P <= 0.05) and SNPs in 102 miRNAs and 1387 associations with 478 target genes. Among these, 102 miRNA-target pairs associated with the same traits. Multi-SNP associations found 102 epistatic pairs associated with traits. Furthermore, a reconstructed regulatory network contained 12 significantly co-expressed pairs, including eight miRNAs and nine targets associated with traits. Lastly, both expression and genetic association showed that miR156i, miR156j, miR396a and miR6445b were involved in the formation of tension wood. This study shows that variants in miRNAs and target genes contribute to natural phenotypic variation and annotated roles and interactions of miRNAs and their target genes by genetic association analysis. PMID- 27265358 TI - Enhancing the versatility of wireless biopotential acquisition for myoelectric prosthetic control. AB - OBJECTIVE: A significant challenge in rehabilitating upper-limb amputees with sophisticated, electric-powered prostheses is sourcing reliable and independent channels of motor control information sufficient to precisely direct multiple degrees of freedom simultaneously. APPROACH: In response to the expressed needs of clinicians, we have developed a miniature, batteryless recording device that utilizes emerging integrated circuit technology and optimal impedance matching for magnetic resonantly coupled (MRC) wireless power transfer to improve the performance and versatility of wireless electrode interfaces with muscle. MAIN RESULTS: In this work we describe the fabrication and performance of a fully wireless and batteryless EMG recording system and use of this system to direct virtual and electric-powered limbs in real-time. The advantage of using MRC to optimize power transfer to a network of wireless devices is exhibited by EMG collected from an array of eight devices placed circumferentially around a human subject's forearm. SIGNIFICANCE: This is a comprehensive, low-cost, and non proprietary solution that provides unprecedented versatility of configuration to direct myoelectric prostheses without wired connections to the body. The amenability of MRC to varied coil geometries and arrangements has the potential to improve the efficiency and robustness of wireless power transfer links at all levels of upper-limb amputation. Additionally, the wireless recording device's programmable flash memory and selectable features will grant clinicians the unique ability to adapt and personalize the recording system's functional protocol for patient- or algorithm-specific needs. PMID- 27265359 TI - A Case of Novel Lamin A/C Mutation Manifesting as Atypical Progeroid Syndrome and Cardiomyopathy. AB - Mutations in the gene LMNA cause a wide spectrum of diseases that selectively affect different tissues and organ systems. The clinical features of these disorders can overlap but be generally categorized into 2 groups: cardiomyopathy and neuromuscular disorders; premature aging and lipodystrophy disorders. It is significant for a single patient who harbours the 2 sets of diseases simultaneously. We present a female patient with a unique phenotype including rare atypical progeroid syndrome and dilated cardiomyopathy. Genetic mutation detection in the gene LMNA revealed a novel heterozygous de novo mutation p.Leu59Val located in the first exon of gene LMNA c.175C>CG. PMID- 27265360 TI - Outcomes of Patients With ST-Elevation Myocardial Infarction Receiving and Not Receiving Reperfusion Therapy: The Importance of Examining All Patients. AB - BACKGROUND: Hospitals treating patients with ST-elevation myocardial infarction (STEMI) may show good results with reperfusion treatment (fibrinolysis or primary percutaneous coronary intervention [PPCI]), but a comprehensive evaluation should factor in outcomes of patients with STEMI who do not receive reperfusion. We compared outcomes of patients receiving and not receiving reperfusion within a complete system of STEMI care by hospital type: PPCI centres, fibrinolysis centres, centres that only transfer for PPCI, and centres providing a mix of fibrinolysis and PPCI transfer. METHODS: All patients presenting to 82 Quebec hospitals with characteristic symptoms, a final diagnosis of acute myocardial infarction, and core-laboratory confirmed STEMI over two 6-month periods were studied. RESULTS: Of the total 3731 patients with STEMI, 2918 (78.2%) received reperfusion treatment (81% PPCI, 19% fibrinolysis); 813 (21.8%) did not. For reperfusion-treated patients, 30-day mortality was 5.4% in PPCI centres, 5.4% in fibrinolysis centres, 6.9% in transfer PPCI centres, and 6.0% in mixed centres (P = 0.55). For untreated patients, 30-day mortality was 15.7% (PPCI centres), 16.1% (fibrinolysis centres), 21.8% (transfer PPCI), and 24.6% (mixed) (P = 0.08). Adjusted mortality odds ratios for all patients were 1.00 (PPCI centres), 1.50 (95% CI: 0.97-2.32; fibrinolysis centres), 1.30 (0.95-1.78; transfer PPCI centres), and 1.58 (1.09-2.29; mixed centres). PPCI was within recommended delays in 35.4%, 11.9%, and 1.2% of PPCI, transfer, and mixed centres, respectively. CONCLUSIONS: Mixed centres had the highest crude and adjusted all-patient 30-day STEMI mortality. Relatively good outcomes of reperfusion-treated patients, despite long treatment delays, can misrepresent overall performance if untreated patients are not examined. PMID- 27265361 TI - Comparison of induction of labor methods for unfavorable cervices in trial of labor after cesarean delivery. AB - OBJECTIVE: To compare induction of labor methods in patients attempting a trial of labor after cesarean (TOLAC) with an unfavorable cervix. METHODS: This is a retrospective cohort study from patients attempting TOLAC from 2009 to 2013. Patients with a simplified Bishop score of three or less where labor was initiated with either a Cook balloon or oxytocin were included. Our primary outcome was mode of delivery. Our secondary outcomes included duration of labor and multiple maternal and neonatal morbidities. RESULTS: Two-hundred and fourteen women met inclusion criteria: 150 received oxytocin and 64 had the Cook balloon placed. The vaginal birth after cesarean delivery rate was significantly higher in the oxytocin group at 70.7% versus 50.0% in the Cook balloon group (p = 0.004). In the multivariable analysis, odds for cesarean delivery were two times higher with the Cook balloon than with oxytocin (Adjusted OR = 2.09, 95% CI = 1.05-4.18, p = 0.036). The duration of labor was longer with the Cook balloon versus oxytocin (21.9 versus 16.3 hours, p = 0.0002). There were no significant differences in maternal and neonatal health outcomes. CONCLUSION: Oxytocin induction of labor was associated with a higher rate of vaginal delivery and a shorter duration of labor compared to the Cook balloon in women undergoing TOLAC with an unfavorable cervix. PMID- 27265363 TI - Cancer genetics: Evading antitumour immunity. PMID- 27265364 TI - Evolution: Duplicate gene co-regulation slows evolution. PMID- 27265365 TI - Metagenomics: Pathogen diagnostics for the masses. PMID- 27265362 TI - Determinants of genetic diversity. AB - Genetic polymorphism varies among species and within genomes, and has important implications for the evolution and conservation of species. The determinants of this variation have been poorly understood, but population genomic data from a wide range of organisms now make it possible to delineate the underlying evolutionary processes, notably how variation in the effective population size (Ne) governs genetic diversity. Comparative population genomics is on its way to providing a solution to 'Lewontin's paradox' - the discrepancy between the many orders of magnitude of variation in population size and the much narrower distribution of diversity levels. It seems that linked selection plays an important part both in the overall genetic diversity of a species and in the variation in diversity within the genome. Genetic diversity also seems to be predictable from the life history of a species. PMID- 27265366 TI - Impaired metabolic profile is a predictor of capillary rarefaction in a population of hypertensive and normotensive individuals. AB - Capillary rarefaction is typically encountered in essential hypertension, yet identification of factors interfering with this phenomenon remains substantially underinvestigated. We examined whether components of metabolic profile (dyslipidemia, insulin resistance), inflammatory (high-sensitivity C-reactive protein, high-sensitivity C-reactive protein), and angiogenic (vascular endothelial growth factor) factors are implicated in this phenomenon in a population of newly diagnosed, never-treated hypertensive patients and normotensive controls. Nailfold capillary density was estimated with nailfold capillaroscopy using specifically designed software. A total of 159 individuals, 93 hypertensives, and 66 normotensives were included. Nailfold capillary density was lower among hypertensives compared to normotensives (146.4 +/- 31.0 vs. 155.4 +/- 26.9, respectively; P = .047). In the total population, capillary density significantly correlated with high-density lipoprotein (HDL) (r = 0.232; P = .003), HDL/low-density lipoprotein ratio (r = 0.175; P = .025), age (r = 0.236; P = .003), but neither with vascular endothelial growth factor or high-sensitivity C-reactive protein. An inverse association was found with body mass index (r = 0.174; P = .029), insulin levels (r = -0.200; P = .018), and homeostasis model assessment-insulin resistance (r = -0.223; P = .009). In the separate analysis for the hypertensive population, sex (P = .014) and homeostasis model assessment insulin resistance (P = .011) were identified as significant predictors of capillary rarefaction after adjustment for other factors. On the contrary, only HDL levels (P = .036) predicted capillary density in the multiple regression model for the normotensive population. Different aspects of impaired metabolic profile, that is, insulin resistance and low HDL levels, but not angiogenic or inflammatory markers, appear to be independently associated with capillary rarefaction in hypertensive and normotensive individuals. PMID- 27265370 TI - A systems biology approach to reconcile metabolic network models with application to Synechocystis sp. PCC 6803 for biofuel production. AB - Production of biofuels has been one of the promising efforts in biotechnology in the past few decades. The perspective of these efforts can be reduction of increasing demands for fossil fuels and consequently reducing environmental pollution. Nonetheless, most previous approaches did not succeed in obviating many big challenges in this way. In recent years systems biology with the help of microorganisms has been trying to overcome these challenges. Unicellular cyanobacteria are widespread phototrophic microorganisms that have capabilities such as consuming solar energy and atmospheric carbon dioxide for growth and thus can be a suitable chassis for the production of valuable organic materials such as biofuels. For the ultimate use of metabolic potential of cyanobacteria, it is necessary to understand the reactions that are taking place inside the metabolic network of these microorganisms. In this study, we developed a Java tool to reconstruct an integrated metabolic network of a cyanobacterium (Synechocystis sp. PCC 6803). We merged three existing reconstructed metabolic networks of this microorganism. Then, after modeling for biofuel production, the results from flux balance analysis (FBA) disclosed an increased yield in biofuel production for ethanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol, and propanol. The numbers of blocked reactions were also decreased for 2-methyl-1-butanol production. In addition, coverage of the metabolic network in terms of the number of metabolites and reactions was increased in the new obtained model. PMID- 27265371 TI - Lethal exposure: An integrated approach to pathogen transmission via environmental reservoirs. AB - To mitigate the effects of zoonotic diseases on human and animal populations, it is critical to understand what factors alter transmission dynamics. Here we assess the risk of exposure to lethal concentrations of the anthrax bacterium, Bacillus anthracis, for grazing animals in a natural system over time through different transmission mechanisms. We follow pathogen concentrations at anthrax carcass sites and waterholes for five years and estimate infection risk as a function of grass, soil or water intake, age of carcass sites, and the exposure required for a lethal infection. Grazing, not drinking, seems the dominant transmission route, and transmission is more probable from grazing at carcass sites 1-2 years of age. Unlike most studies of virulent pathogens that are conducted under controlled conditions for extrapolation to real situations, we evaluate exposure risk under field conditions to estimate the probability of a lethal dose, showing that not all reservoirs with detectable pathogens are significant transmission pathways. PMID- 27265372 TI - Interleukin-2 as a marker for detecting asymptomatic individuals in areas where Leishmania infantum is endemic. AB - No field method exists for identifying asymptomatic individuals in areas where Leishmania infantum is endemic. This work reports that, 24 h after stimulating whole blood with soluble Leishmania antigen (SLA), plasma interferon-gamma (IFN gamma) and interleukin-2 (IL-2) become significantly elevated in samples from asymptomatic individuals (n=47) compared with those from negative controls (n=50), all of them recruited from a blood bank. When compared with the reference test SLA-lymphoproliferative assay, IL-2 appears as a new, 100% sensitive and specific marker for asymptomatic individuals with a positive cellular response (compared with 100% and 84.78%, respectively, for IFN-gamma). Further studies in other transmission areas and in other cohorts of exposed people need to be performed to confirm these results. Once validated, IFN-gamma and IL-2 levels in SLA-stimulated whole blood could be reliably used in the field to estimate the prevalence of those asymptomatic individuals with Leishmania-specific cellular immune responses. PMID- 27265373 TI - Prevalence of rhinoviruses in young children of an unselected birth cohort from the Netherlands. AB - Rhinovirus (RV) is a frequent pathogen in young children, eliciting symptoms ranging from common colds to wheezing illnesses and lower respiratory tract infections. The recently identified RV-C seems to be associated with asthma exacerbations and more severe disease, but results vary. We studied the prevalence and severity of infection with RV in an unselected birth cohort. Children with respiratory symptoms entered the symptomatic arm of the cohort and were compared with asymptomatic children. Severity of wheezing and other respiratory symptoms was registered. Respiratory viruses were evaluated using throat and nasopharyngeal swabs on first presentation and after recovery (wheezing children). RV genotyping was performed on RV-PCR positive samples. RV was the most prevalent respiratory virus and was found in 58/140 symptomatic children (41%), 24/96 (25%) control children and 19/74 (26%) wheezing symptomatic children after recovery (p <0.05) and did not differ between wheezing and non wheezing symptomatic children-respectively, 42% (38/90) and 40% (20/50). RV-A was the most commonly detected species (40/68, 59%), followed by RV-C (22/68, 32%) and RV-B (6/68, 9%). RV-B was more frequently detected in asymptomatic children (5/6, p <0.05). There was no significant difference in the frequency of RV species between wheezing and non-wheezing symptomatic children. Children with RV mono-infection had more severe symptoms, but no association between RV species and severity of disease was seen. In an unselected birth cohort from the Netherlands with mild respiratory disease RV was the most prevalent respiratory virus. RV(-C) infection was not associated with more severe disease or wheezing. PMID- 27265374 TI - Sister chromatid exchange assay as a predictor of tumor chemoresponse. AB - Sister Chromatid Exchanges (SCEs) are known to enhance as a consequence of exposure to various mutagenic agents and appear to indicate DNA damaging effects and/or subsequent repair by homologous recombination (HR). DNA damage plays an interesting role in the majority of mechanisms underlying the effects of antitumor drugs, since the genetic activity of the plethora of these agents is due to their ability to damage the DNA. The DNA-effects of antitumor agents towards normal cells (genotoxicity) are great drawbacks of antitumor therapy and are connected to important adverse health effects in cancer patients undergoing chemotherapy. On the other hand, failure of chemotherapy in many cases is due to the DNA repair ability which cancer, like normal cells, also possess. As both DNA repair and genotoxic exposure are expected to vary among patients, correlating SCEs frequencies with only individual repair capacity may be feasible to predict. Cancer risk has not been observed to be associated with high SCEs levels. Since the administration of effective antitumor drugs with limited adverse effects is of great importance in the success of anticancer therapy, a lot of interest has been directed toward the development of methods and approaches that would enable the correct selection of appropriate drugs prior to the initiation of therapy on an individual basis. To this effect, more than 30 years ago, an investigation of the ability of the in vitro and the in vivo SCEs-assay to predict the in vitro and in vivo sensitivity of tumor cells to newly synthesized drugs or to those already in use began. In this short review a critical appraisal of the SCEs-assay as an important biomarker used for predicting cancer chemo-response as well as a summary of the key findings from several studies published within the last 20 years in this field is performed. PMID- 27265375 TI - Assessing the mutagenic activities of smoke from different cigarettes in direct exposure experiments using the modified Ames Salmonella assay. AB - The Ames assay is useful for evaluating the mutagenic potentials of chemicals, and it has been used to evaluate the mutagenic potential of cigarette smoke (CS). In vitro direct exposure systems have been developed to mimic CS exposure in the human respiratory tract, and the Ames assay has been used with such systems. Ames tests were performed using the Vitrocell((r)) direct exposure system in this study. The mutagenic potentials of whole mainstream CS and gas/vapor phase fractions produced by conventional combustible cigarettes under two smoking regimens were compared. Salmonella Typhimurium TA98 and TA100 were used with and without metabolic activation, and the number of revertants induced by exposure to each CS was determined. The amount of smoke particles to which cells were exposed were also determined, and dose-response curves describing the relationships between exposure to smoke particles and the number of revertants induced were plotted. The slopes of linear regressions of the dose-response curves were determined, and the slope for each CS was used as a mutagenic activity index for that CS. A new heated cigarette was also tested and smoke from the heated cigarette had a lower mutagenic activity in TA98 and TA100 with metabolic activation than did the conventional CS. The results indicate that the direct exposure system and the Ames test can be used to determine the mutagenic potentials of CS produced by different cigarettes under different conditions (i.e., using different Salmonella Typhimurium strains with and without metabolic activation, and using different smoking conditions). PMID- 27265376 TI - Different sensitivities of cultured mammalian cells towards aphidicolin-enhanced DNA effects in the comet assay. AB - The comet assay in combination with the polymerase inhibitor aphidicolin (APC) has been used to measure DNA excision repair activity, DNA repair kinetics and individual DNA repair capacity. Since APC can enhance genotoxic effects of mutagens measured by the comet assay, this approach has been proposed for increasing the sensitivity of the comet assay in human biomonitoring. The APC modified comet assay has mainly been performed with human blood and it was shown that it not only enhances the detection of DNA damage repaired by nucleotide excision repair (NER) but also damage typically repaired by base excision repair (BER). Recently, we reported that in contrast to blood leukocytes, A549 cells (a human lung adenocarcinoma cell line) seem to be insensitive towards the repair inhibiting action of APC. To further elucidate the general usefulness of the APC modified comet assay for studying repair in cultured mammalian cells, we comparatively investigated further cell lines (HeLa, TK6, V79). DNA damage was induced by BPDE (benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide) and MMS (methyl methanesulfonate) in the absence and presence of APC (3 or 15MUM). APC was either added for 2h together with the mutagen or cells were pre-incubated for 30min with APC before the mutagen was added. The results indicate that the cell lines tested differ fundamentally with regard to their sensitivity and specificity towards the repair-inhibiting effect of APC. The actual cause for these differences is still unclear but potential molecular explanations are discussed. Irrespective of the underlying mechanism(s), our study revealed practical limitations of the use of the APC-modified comet assay. PMID- 27265377 TI - Monitoring genotoxicity in freshwater microcrustaceans: A new application of the micronucleus assay. AB - We have applied the micronucleus (MN) assay to the measurement of genotoxicity in microcrustaceans. Daphnids (Daphnia magna) and Copepods (Acanthocyclops robustus) were collected in situ and acclimated in the lab for 24h. The MN assay was successful with the Daphnids but not with the Copepods. Adult Daphnids were exposed to sublethal concentrations of metals (Cu, Zn, Cd) or insecticide (deltamethrin) for 2 and 7d. Dose-dependent induction of MN was observed after 2 d exposure, with 2-fold induction at the highest doses for each chemical tested. The advantages and ecological relevance of using Daphnids in genotoxicity assessment are highlighted. The Daphnid assay may be a reliable test for aquatic genotoxicity hazard/risk assessment and a useful alternative to studies of amphibians. PMID- 27265378 TI - 2.3THz radiation: Absence of genotoxicity/mutagenicity in Escherichia coli and Salmonella typhimurium. AB - The mutagenicity and genotoxicity in bacteria of 2.3THz radiation (THz) produced by a free-electron laser (NovoFEL) were evaluated; exposures were 5, 10, or 15min at average power 1.4W/cm(2). Two Ames mutagenicity test strains of Salmonella typhimurium, TA98 and TA102, were used. For the genotoxicity test, we measured SOS induction in Escherichia coli PQ37. No significant differences were found between exposed and control cells, indicating that THz radiation is neither mutagenic nor genotoxic under these conditions. Nevertheless, a small increase in total cell number of S. typhimurium after 15min exposure, and an increase in beta galactosidase and alkaline phosphatase activities in E.coli PQ37, were observed, indicating some effect of THz radiation on cell metabolism. We also examined the combined effect of 4-NQO (8MUM; positive control) and THz exposure (5min) on genotoxicity in E.coli PQ37. Unexpectedly, THz radiation decreased 4-NQO genotoxicity. PMID- 27265379 TI - Impeded repair of abasic site damaged lesions in DNA adsorbed over functionalized multiwalled carbon nanotube and graphene oxide. AB - The processing of abasic site DNA damage lesions in extracellular DNA in the presence of engineered carbon nanomaterials (CNMs) is demonstrated. The efficacy of the apurinic-apyrimidinic endonuclease 1 (APE1) in the cleavage of abasic site lesions in the presence of carboxylated multi-walled carbon nanotubes (MWCNT COOH) and graphene oxide (GO) are compared. The CNMs were found to perturb the incision activity of APE1. The reason for such perturbation process was anticipated to take place either by the non-specific adsorption of APE1 over the free surface of the CNMs or steric hindrance offered by the CNM-DNA complex. Accordingly, bovine serum albumin (BSA) was selectively utilized to block the free surface of the CNM-DNA hybrid material. Further treatment of the CNM-DNA-BSA complex with APE1 resulted in a marginal increase in APE1 efficiency. This indicates that APE1 in solution is unable to process the abasic sites on DNA adsorbed over the CNMs. However, the cleavage activity of APE1 was restored in the presence of non-ionic surfactant (Tween 20) that inhibits adsorption of the DNA on the surface of the CNMs. The conformational deformation of the DNA, along with steric hindrance induced by the CNMs resulted in the inhibition of abasic site DNA repair by APE1. Moreover, appreciable changes in the secondary structure of APE1 adsorbed over the CNMs were observed that contribute further to the repair refractivity of the abasic sites. From a toxicological viewpoint, these findings can be extended to the study of the effect of engineered nanoparticles in the intracellular DNA repair process. PMID- 27265380 TI - Reversible Bending Behaviors of Photomechanical Soft Actuators Based on Graphene Nanocomposites. AB - Photomechanical nanocomposites embedded with light-absorbing nanoparticles show promising applications in photoresponsive actuations. Near infrared (nIR) responsive nanocomposites based photomechanical soft actuators can offer lightweight functional and underexploited entry into soft robotics, active optics, drug delivery, etc. A novel graphene-based photomechanical soft actuators, constituted by Polydimethylsiloxane (PDMS)/graphene-nanoplatelets (GNPs) layer (PDMS/GNPs) and pristine PDMS layer, have been constructed. Due to the mismatch of coefficient of thermal expansion of two layers induced by dispersion of GNPs, controllable and reversible bendings response to nIR light irradiation are observed. Interestingly, two different bending behaviors are observed when the nIR light comes from different sides, i.e., a gradual single step photomechanical bending towards PDMS/GNPs layer when irradiation from PDMS side, while a dual-step bending (finally bending to the PDMS/GNPs side but with an strong and fast backlash at the time of light is on/off) when irradiation from PDMS/GNPs side. The two distinctive photomechanical bending behaviors are investigated in terms of heat transfer and thermal expansion, which reveals that the distinctive bending behaviors can be attributed to the differences in temperature gradients along the thickness when irradiation from different sides. In addition, the versatile photomechanical bending properties will provide alternative way for drug-delivery, soft robotics and microswitches, etc. PMID- 27265381 TI - [Compliance with the surgical safety checklist and surgical events detected by the Global Trigger Tool]. AB - INTRODUCTION: The implementing of the WHO Surgical Safety Checklist (SSC) has helped to improve patient safety. The aim of this study was to assess the level of compliance of the SSC, and incorporating the non-compliances as "triggers" in the Global Trigger Tool (GTT). MATERIAL AND METHODS: SETTING: Acute Geriatric Hospital (200 beds). Retrospective study, study period: 2011-2014. The SSC formulary and the methodology of the GTT were used for the analysis of electronic medical records and the compliance with the SSC. The NCCP MERP categories were used to assess the severity of the harm. RESULTS: Out of all the electronic medical records (EMR), a total of 227 (23.6%) discharged patients (1.7% of interventions in the four year study period) were analysed. All (100%) of the EMR included the SSC, with 94.4% of the items being completed, and 28.2% of SSC had all items completed in the 3 phases of the process. Surgical adverse events decreased from 16.3% in 2011 to 9.4% in 2014 (P=.2838, not significant), and compliance with all items of SSC was increased from 18.6% to 39.1% (P=.0246, significant). CONCLUSIONS: The GTT systematises and evaluates, at low cost, the triggers and incidents/ AEs found in the EMR in order to assess the compliance with the SSC and consider non-compliance of SSC as "triggers" for further analysis. This strategy has never been referred to in the GTT or in the SCC formulary. PMID- 27265382 TI - [Medication reconciliation in patients over 75 years]. AB - OBJECTIVE: To continue with the implementation of the medication reconciliation process on admission, and to analyse potentially inappropriate prescriptions according to the STOPP-START -Screening Tool of Older Person's potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right (indicated) Treatment- criteria, and drug interactions. To extend the process of reconciliation at hospital discharge from the Cardiology and Chest Diseases departments. MATERIAL AND METHODS: Retrospective observational study that included patients over 75 years old. The "Consensus Document on Terminology and Classification in Medication Reconciliation" was used for the classification of the discrepancies found. Potentially inappropriate prescriptions and drug interactions were reviewed. For reconciliation at discharge, a "Drug information program at discharge" leaflet and a "Patient information sheet" was developed. RESULTS: The number of reconciled patients was 818, with a level of coverage of 42.3% (target patients: 1,932). Reconciliation errors by patient were 23.4% (191) on admission and 22.5% (9) at discharge. All patients who were reconciled at discharge were given the "Drug information program at discharge" leaflet. Potentially inappropriate prescriptions, according to STOPP/START criteria, affected 6.0% (49) of reconciled patients. The number of clinically relevant interactions affected 11.7% (96) of patients. CONCLUSIONS: The implementation of a reconciliation process has detected the existence of errors between chronic and prescribed treatment in the hospital. The STOPP/START criteria applied to this group of patients have helped to find out the most common potentially inappropriate prescriptions. The analysis of drug interactions shows drug combinations that should be avoided in these patients. PMID- 27265383 TI - [Self-perception of health care team leaders in Andalusia. A quantitative and qualitative study]. AB - OBJECTIVE: To determine the perception and self-assessment on leadership among health care team leaders in Andalusia. MATERIAL AND METHODS: Design: Exploratory descriptive study using quantitative and qualitative methodology, developed between 2013 and 2015, using a questionnaire and semi-structured interviews. PLACE: Andalusia. PARTICIPANTS: All health managers from the Primary Care Management Units and Health Management Areas of the Departments of Paediatrics, Emergency and Internal Medicine, for the quantitative study. A purposive sample of 24 health managers was used for the qualitative study. METHODS: Descriptive statistical study and bivariate analysis of comparison of means. Content analysis of the semi-structured interviews: Codification, category tree, and triangulation of results. RESULTS: The best self-assessment dimension relates to support, and the worst to considering oneself as a 'good leader'. The definition of a 'good leader' includes: Honesty, trust, and attitudes of good communication, closeness, appreciation, and reinforcement of the health team members. Different leadership styles were perceived. Main difficulties for leadership are related to the economic crisis and the management of personal conflicts. CONCLUSIONS: Health managers describe an adaptive leadership style, based on personal and professional support, and using communication as the main cohesive element for the team project. More studies on leaders' perspectives are important, in order to better understand their experiences, needs and expectations. PMID- 27265384 TI - Dihydromyricetin ameliorates oleic acid-induced lipid accumulation in L02 and HepG2 cells by inhibiting lipogenesis and oxidative stress. AB - AIMS: Dihydromyricetin (DMY), a flavonoid component isolated from Ampelopsis grossedentata, was recently reported to ameliorate nonalcoholic fatty liver disease (NAFLD) in patients. However, the underlying mechanisms of this action remain unknown. Here, we evaluate the effect of DMY on an in vitro model of NAFLD and investigate the signal transduction pathways underlying DMY treatment. MAIN METHODS: Oleic acid (OA) induced hepatic steatosis was established in L02 and HepG2 cells as in vitro model of NAFLD. Cell apoptosis, lipid accumulation and oxide stress were evaluated by flow cytometry, oil red O staining, and cellular biochemical assays, respectively. Signaling pathways involved in lipid metabolism including PPARgamma, AMPK, and AKT were investigated by Western blot and RT-qPCR. KEY FINDINGS: DMY protected cells against apoptosis and lipid accumulation induced by oleic acid. DMY decreased the levels of cellular triglycerides (TG), cholesterol (TC) and malondialdehyde (MDA), while at the same time increasing the level of superoxide dismutase (SOD). DMY suppressed the expression of PPARgamma and the phosphorylation of AKT, and promoted the phosphorylation of AMPK. SIGNIFICANCE: Our study suggests that DMY ameliorates OA-induced hepatic steatosis by inhibiting cell apoptosis, lipid accumulation and oxide stress. Furthermore, the effect of DMY is likely associated with its role in the regulating of PPARgamma, AMPK and AKT signaling pathways. PMID- 27265385 TI - Fulleretic Well-Defined Scaffolds: Donor-Fullerene Alignment Through Metal Coordination and Its Effect on Photophysics. AB - Herein, we report the first example of a crystalline metal-donor-fullerene framework, in which control of the donor-fullerene mutual orientation was achieved through chemical bond formation, in particular, by metal coordination. The (13) C cross-polarization magic-angle spinning NMR spectroscopy, X-ray diffraction, and time-resolved fluorescence spectroscopy were performed for comprehensive structural analysis and energy-transfer (ET) studies of the fulleretic donor-acceptor scaffold. Furthermore, in combination with photoluminescence measurements, the theoretical calculations of the spectral overlap function, Forster radius, excitation energies, and band structure were employed to elucidate the photophysical and ET processes in the prepared fulleretic material. We envision that the well-defined fulleretic donor-acceptor materials could contribute not only to the basic science of fullerene chemistry but would also be used towards effective development of organic photovoltaics and molecular electronics. PMID- 27265386 TI - Cognition in relation to independency in older, comorbid stroke patients in a stroke unit. AB - OBJECTIVE: The objective of this study was to ascertain if cognition helps to predict functional outcome in older comorbid stroke patients with severe loss of independence. DESIGN: This is a cross-sectional study. SUBJECTS: The subjects of this study are patients who have suffered a stroke and who rehabilitated in the nursing homes' rehabilitation units and patients (n = 160) (mean age: 77; SD: 9.5) with a mean Barthel Index of 11.02. METHOD: Demographic, illness-related, functional and cognitive data were selected at baseline. MAIN ASSESSMENT MEASURES: Functional abilities were tested using the Barthel Index. Cognitive functions were assessed using a wide variety of neuropsychological tests. RESULTS: Patients faced cognitive impairments especially in executive functioning and memory. Stepwise linear regression analysis shows that executive functioning (p = 0.050) and memory (p = 0.000; confidence interval -1.255, -0.403) are significantly associated with functional outcome. CONCLUSION: From a clinical point of view, we suggest combining physical and cognitive training from the very early phase of recovery. PMID- 27265387 TI - More than skin deep. Ten year follow-up of delayed cutaneous adverse drug reactions (CADR). AB - AIMS: To determine the gaps in practice regarding appropriate ADR documentation and risk communication for patients diagnosed with severe cutaneous adverse drug reactions (CADR). METHODS: This was a retrospective observational cohort study conducted using hospital coding and databases to identify inpatients diagnosed with CADR from January 2004 to August 2014. Hospital discharge summaries, ADR reports and pharmacy dispensing records were reviewed for ADR documentation. Patients still living in Australia and who did not opt out of being contacted were invited to be surveyed by telephone to determine their understanding of recommendations, re-exposure rates and long-term effects. RESULTS: Of 85 patients identified, median age was 59 (IQR 44-72) years and 47.1% were male. The most common diagnosis was TENS (49.4%). Ten patients (11.8%) died as inpatients. Of the 81 patients with a drug-related causality, 47 (58%) had appropriate documentation in all three required medical record platforms. Of the 56 eligible patients, 38 (67.9%) were surveyed; 13% had no information provided upon discharge and 26.3% patients had a mismatch in knowledge of implicated medications. No surveyed patient had a relapse of CADR, but 23.7% had a subsequent unrelated allergic reaction. Thirteen patients (34.2%) reported long term effects. CONCLUSIONS: We found gaps in the accuracy of ADR documentation and communication of risk at discharge, which indicated risks to patient safety. Electronic systems are being developed to improve documentation. Written information about CADR is being provided at discharge to improve patient understanding and knowledge. PMID- 27265388 TI - Effects of dark chocolate on NOX-2-generated oxidative stress in patients with non-alcoholic steatohepatitis. AB - BACKGROUND: Activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is considered a pathogenetic mechanism determining fibrosis and disease progression in non-alcoholic steatohepatitis (NASH). Polyphenols exert antioxidant action and inhibit NADPH oxidase in humans. AIM: To analyse the effect of cocoa polyphenols on NADPH oxidase isoform 2 (NOX2) activation, oxidative stress and hepatocyte apoptosis in a population affected by NASH. METHODS: In a cross-sectional study comparing 19 NASH and 19 controls, oxidative stress, as assessed by serum NOX2 activity and F2-isoprostanes, and hepatocyte apoptosis, as assessed by serum cytokeratin-18 (CK-18) levels, were measured. Furthermore, the 19 NASH patients were randomly allocated in a crossover design to 40 g/day of dark chocolate (>85% cocoa) or 40 g/day of milk chocolate (<35% cocoa), for 2 weeks. sNOX2-dp, serum isoprostanes and CK-18 were assessed at baseline and after 2 weeks of chocolate intake. RESULTS: Compared to controls, NASH patients had higher sNOX2-dp, serum isoprostanes and CK-18 levels. A significant difference for treatments was found in subjects with respect to sNOX2 dp, serum isoprostanes and serum CK-18. The pairwise comparisons showed that, compared to baseline, after 14 days of dark chocolate intake, a significant reduction in sNOX2-dp serum isoprostanes and CK-18 M30 was found. No change was observed after milk chocolate ingestion. A simple linear regression analysis showed that ? of sNOX2-dp was associated with ? of serum isoprostanes. CONCLUSION: Cocoa polyphenols exert an antioxidant activity via NOX2 down regulation in NASH patients. PMID- 27265390 TI - Randomized, double-blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3. AB - AIMS: To compare the efficacy and safety of basal insulin peglispro (BIL), which has a flat pharmacokinetic and pharmacodynamic profile and a long duration of action, with insulin glargine (GL) in patients with type 1 diabetes. MATERIALS AND METHODS: In this phase III, 52-week, blinded study, we randomized 1114 adults with type 1 diabetes in a 3 : 2 distribution to receive either BIL (n = 664) or GL (n = 450) at bedtime, with preprandial insulin lispro, using intensive insulin management. The primary objective was to compare glycated haemoglobin (HbA1c) in the groups at 52 weeks, with a non-inferiority margin of 0.4%. RESULTS: At 52 weeks, mean (standard error) HbA1c was 7.38 (0.03)% with BIL and 7.61 (0.04)% with GL {difference -0.22% [95% confidence interval (CI) -0.32, -0.12]; p < 0.001}. At 52 weeks more BIL-treated patients reached HbA1c <7% (35% vs 26%; p < 0.001), the nocturnal hypoglycaemia rate was 47% lower (p < 0.001) and the total hypoglycaemia rate was 11% higher (p = 0.002) than in GL-treated patients, and there was no difference in severe hypoglycaemia rate. Patients receiving BIL lost weight, while those receiving GL gained weight [difference -1.8 kg (95% CI -2.3, 1.3); p < 0.001]. Treatment with BIL compared with GL at 52 weeks was associated with greater increases from baseline in levels of serum triglyceride [difference 0.19 mmol/l (95% CI 0.11, 0.26); p < 0.001] and alanine aminotransferase (ALT) levels [difference 6.5 IU/l (95% CI 4.1, 8.9), p < 0.001], and more frequent injection site reactions. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared with GL for 52 weeks resulted in a lower HbA1c, more patients with HbA1c levels <7%, and reduced nocturnal hypoglycaemia, but more total hypoglycaemia and injection site reactions and higher triglyceride and ALT levels. PMID- 27265391 TI - Gonadal Maturation Changes Chemotaxis Behavior and Neural Processing in the Olfactory Circuit of Caenorhabditis elegans. AB - Many animal species change their behavior according to their stage of development. However, the mechanisms involved in translating their developmental stage into the modifications of the neuronal circuits that underlie these behavioral changes remain unknown. Here we show that Caenorhabditis elegans changes its olfactory preferences during development. Larvae exhibit a weak chemotactic response to the food-associated odor diacetyl, whereas adults exhibit a strong response. We show that germline loss, caused either by laser ablation of germline precursor cells or mutations, results in a diacetyl-specific chemotactic defect in adult animals. These results suggest that germline cells, which proliferate dramatically during the larval stages, enhance chemotaxis to diacetyl. Removal experiments of specific neurons suggested that AWA olfactory neurons and their downstream interneurons, AIA and AIB, are required for germline dependent chemotactic enhancement. Calcium imaging in animals lacking germline cells indicates that the neural responses of AWA and AIB to diacetyl stimuli are decreased compared with animals with an intact germline. These changes in neural activities may at least partly explain the behavioral change of animals lacking germline cells. Furthermore, this germline-dependent chemotactic change depends on the transcription factor DAF-16/FOXO. We find that organismal behavior changes throughout development by integrating information about physiological status from internal tissues to modify a simple sensory circuit. PMID- 27265389 TI - Involvement of human ribosomal proteins in nucleolar structure and p53-dependent nucleolar stress. AB - The nucleolus is a potent disease biomarker and a target in cancer therapy. Ribosome biogenesis is initiated in the nucleolus where most ribosomal (r-) proteins assemble onto precursor rRNAs. Here we systematically investigate how depletion of each of the 80 human r-proteins affects nucleolar structure, pre rRNA processing, mature rRNA accumulation and p53 steady-state level. We developed an image-processing programme for qualitative and quantitative discrimination of normal from altered nucleolar morphology. Remarkably, we find that uL5 (formerly RPL11) and uL18 (RPL5) are the strongest contributors to nucleolar integrity. Together with the 5S rRNA, they form the late-assembling central protuberance on mature 60S subunits, and act as an Hdm2 trap and p53 stabilizer. Other major contributors to p53 homeostasis are also strictly late assembling large subunit r-proteins essential to nucleolar structure. The identification of the r-proteins that specifically contribute to maintaining nucleolar structure and p53 steady-state level provides insights into fundamental aspects of cell and cancer biology. PMID- 27265393 TI - Fruitless Represses robo1 Transcription to Shape Male-Specific Neural Morphology and Behavior in Drosophila. AB - The Drosophila fruitless (fru) gene is regarded as a master regulator of the formation of male courtship circuitry, yet little is known about its molecular basis of action. We show that roundabout 1 (robo1) knockdown in females promotes formation of the male-specific neurite in sexually dimorphic mAL interneurons and that overexpression of the male-specific Fru(BM) diminishes the expression of Robo1 in the fly brain. Our electrophoretic mobility shift and reporter assays identify the 42-bp segment encompassing the palindrome sequence T T C G C T G C G C C G T G A A in the 5' UTR of robo1 exon1 as the Fru(BM)-responsive element. We find that ~10-bp deletions in the palindrome sequence induce a loss of the male specific neurite and disrupt male courtship patterns. This study paves the way for a thorough understanding of the mechanism whereby Fru proteins orchestrate transcription for the formation of courtship circuitry. PMID- 27265394 TI - Three-Step Model for Polarized Sorting of KIF17 into Dendrites. AB - Kinesin and dynein motors drive bidirectional cargo transport along microtubules and have a critical role in polarized cargo trafficking in neurons [1, 2]. The kinesin-2 family protein KIF17 is a dendrite-specific motor protein and has been shown to interact with several dendritic cargoes [3-7]. However, the mechanism underlying the dendritic targeting of KIF17 remains poorly understood [8-11]. Using live-cell imaging combined with inducible trafficking assays to directly probe KIF17 motor activity in living neurons, we found that the polarized sorting of KIF17 to dendrites is regulated in multiple steps. First, cargo binding of KIF17 relieves autoinhibition and initiates microtubule-based cargo transport. Second, KIF17 does not autonomously target dendrites, but enters the axon where the actin cytoskeleton at the axon initial segment (AIS) prevents KIF17 vesicles from moving further into the axon. Third, dynein-based motor activity is able to redirect KIF17-coupled cargoes into dendrites. We propose a three-step model for polarized targeting of KIF17, in which the collective function of multiple motor teams is required for proper dendritic sorting. PMID- 27265392 TI - Risk Taking for Potential Reward Decreases across the Lifespan. AB - The extent to which aging affects decision-making is controversial. Given the critical financial decisions that older adults face (e.g., managing retirement funds), changes in risk preferences are of particular importance [1]. Although some studies have found that older individuals are more risk averse than younger ones [2-4], there are also conflicting results, and a recent meta-analysis found no evidence for a consistent change in risk taking across the lifespan [5]. There has as yet been little examination of one potential substrate for age-related changes in decision-making, namely age-related decline in dopamine, a neuromodulator associated with risk-taking behavior. Here, we characterized choice preferences in a smartphone-based experiment (n = 25,189) in which participants chose between safe and risky options. The number of risky options chosen in trials with potential gains but not potential losses decreased gradually over the lifespan, a finding with potentially important economic consequences for an aging population. Using a novel approach-avoidance computational model, we found that a Pavlovian attraction to potential reward declined with age. This Pavlovian bias has been linked to dopamine, suggesting that age-related decline in this neuromodulator could lead to the observed decrease in risk taking. PMID- 27265395 TI - Attention Reorients Periodically. AB - Reorienting of voluntary attention enables the processing of stimuli at previously unattended locations. Although studies have identified a ventral fronto-parietal network underlying attention [1, 2], little is known about whether and how early visual areas are involved in involuntary [3, 4] and even less in voluntary [5] reorienting, and their temporal dynamics are unknown. We used transcranial magnetic stimulation (TMS) over the occipital cortex to interfere with attentional reorienting and study its role and temporal dynamics in this process. Human observers performed an orientation discrimination task, with either valid or invalid attention cueing, across a range of stimulus contrasts. Valid cueing induced a behavioral response gain increase, higher asymptotic performance for attended than unattended locations. During subsequent TMS sessions, observers performed the same task, with high stimulus contrast. Based on phosphene mapping, TMS double pulses were applied at one of various delays to a consistent brain location in retinotopic areas (V1/V2), corresponding to the evoked signal of the target or distractor, in a valid or invalid trial. Thus, the stimulation was identical for the four experimental conditions (valid/invalid cue condition * target/distractor-stimulated). TMS modulation of the target and distractor were both periodic (5 Hz, theta) and out of phase with respect to each other in invalid trials only, when attention had to be disengaged from the distractor and reoriented to the target location. Reorientation of voluntary attention periodically involves V1/V2 at the theta frequency. These results suggest that TMS probes theta phase-reset by attentional reorienting and help link periodic sampling in time and attention reorienting in space. PMID- 27265396 TI - Unique Cellular Organization in the Oldest Root Meristem. AB - Roots and shoots of plant bodies develop from meristems-cell populations that self-renew and produce cells that undergo differentiation-located at the apices of axes [1].The oldest preserved root apices in which cellular anatomy can be imaged are found in nodules of permineralized fossil soils called coal balls [2], which formed in the Carboniferous coal swamp forests over 300 million years ago [3-9]. However, no fossil root apices described to date were actively growing at the time of preservation [3-10]. Because the cellular organization of meristems changes when root growth stops, it has been impossible to compare cellular dynamics as stem cells transition to differentiated cells in extinct and extant taxa [11]. We predicted that meristems of actively growing roots would be preserved in coal balls. Here we report the discovery of the first fossilized remains of an actively growing root meristem from permineralized Carboniferous soil with detail of the stem cells and differentiating cells preserved. The cellular organization of the meristem is unique. The position of the Korper-Kappe boundary, discrete root cap, and presence of many anticlinal cell divisions within a broad promeristem distinguish it from all other known root meristems. This discovery is important because it demonstrates that the same general cellular dynamics are conserved between the oldest extinct and extant root meristems. However, its unique cellular organization demonstrates that extant root meristem organization and development represents only a subset of the diversity that has existed since roots first evolved. PMID- 27265397 TI - Saccade Preparation Reshapes Sensory Tuning. AB - Human observers make large rapid eye movements-saccades-to bring behaviorally relevant information into the fovea, where spatial resolution is high. In some visual tasks [1-4], performance at the location of a saccade target improves before the eyes move. Although these findings provide evidence that extra-retinal signals evoked by saccades can enhance visual perception, it remains unknown whether and how presaccadic modulations change the processing of feature information and thus modulate visual representations. To answer this question, one must go beyond the use of methods that only probe performance accuracy (d') in different tasks. Here, using a psychophysical reverse correlation approach [5 8], we investigated how saccade preparation influences the processing of orientation and spatial frequency-two building blocks of early vision. We found that saccade preparation selectively enhanced the gain of high spatial frequency information and narrowed orientation tuning at the upcoming saccade landing position. These modulations were time locked to saccade onset, peaking right before the eyes moved (-50-0 ms). Moreover, merely deploying covert attention within the same temporal interval without preparing a saccade did not alter performance. The observed presaccadic tuning changes may correspond to the presaccadic enhancement [9-11] and receptive field shifts reported in neurophysiological studies [12-14]. Saccade preparation may support transaccadic integration by reshaping the representation of the saccade target to be more fovea-like just before the eyes move. The presaccadic modulations on spatial frequency and orientation processing illustrate a strong perception-action coupling by revealing that the visual system dynamically reshapes feature selectivity contingent upon eye movements. PMID- 27265398 TI - Diversification of a Transcription Factor Family Led to the Evolution of Antagonistically Acting Genetic Regulators of Root Hair Growth. AB - Streptophytes colonized the land some time before 470 million years ago [1-3]. The colonization coincided with an increase in morphological and cellular diversity [4-7]. This increase in diversity is correlated with a proliferation in transcription factors encoded in genomes [8-10]. This suggests that gene duplication and subsequent diversification of function was instrumental in the generation of land plant diversity. Here, we investigate the diversification of the streptophyte-specific Lotus japonicus ROOTHAIRLESS LIKE (LRL) transcription factor (TF) [11, 12] subfamily of basic loop helix (bHLH) proteins by comparing gene function in early divergent and derived land plant species. We report that the single Marchantia polymorpha LRL gene acts as a general growth regulator required for rhizoid development, a function that has been partially conserved throughout multicellular streptophytes. In contrast, the five relatively derived Arabidopsis thaliana LRL genes comprise two antagonistically acting groups of differentially expressed genes. The diversification of LRL genes accompanied the evolution of an antagonistic regulatory element controlling root hair development. PMID- 27265399 TI - The effect of under-reporting of energy intake on dietary patterns and on the associations between dietary patterns and self-reported chronic disease in women aged 50-69 years. AB - The aim of this cross-sectional study was to investigate whether under-reporting of energy intake affects derived dietary patterns and the association between dietary patterns and self-reported chronic disease. Diets of 6204 women aged 50 69 years participating in the Norwegian Breast Cancer Screening Program were assessed using a 253-item FFQ. We identified dietary patterns using principal component analysis. According to the revised Goldberg cut-off method, women with a ratio of reported energy intake:estimated BMR<1.10 were classified as low energy reporters (n 1133, 18 %). We examined the associations between dietary patterns and self-reported chronic diseases by log-binomial regression, and the results are presented as prevalence ratios (PR) and CI. 'Prudent', 'Western' and 'Continental' dietary patterns were identified among all reporters and plausible reporters. The PR expressing the associations between the 'Western' and 'Prudent' dietary pattern scores and self-reported chronic diseases were consistently highest among plausible reporters except for joint/muscle/skeletal disorders. The largest difference in PR among plausible v. all reporters was found for the association between the 'Prudent' pattern and diabetes (PR for highest v. lowest tertile: PRall reporters 2.16; 95 % CI 1.50, 3.13; P trend<0.001; PRplausible reporters 2.86; 95 % CI 1.81, 4.51; P trend<0.001). In conclusion, our results suggest that under-reporting can result in systematic error that can affect the association between dietary pattern and disease. In studies of dietary patterns, investigators ought to consider reporting effect estimates both for all individuals and for plausible reporters. PMID- 27265400 TI - Identification of photoproducts of fungicide cyprodinil and elucidation of transformation mechanism in water using LC-IT-TOF-MS/MS technique. AB - This study aimed at investigating photodegradation of cyprodinil in aquatic solution under the simulated natural light or UV-visible irradiation (290-800 nm) using LC-MS/MS techniques. Effects of pH, nitrate ion, Fe (III), humic acid and TiO2 on photolysis kinetics of cyprodinil were explored. The photodegradation followed first-order reaction kinetics, and linear accelerating effects of Fe (III), nitrate ion and TiO2 with concentrations ranging from 0.1 to 5.0 mg L(-1) on photodegradation were remarkably observed. HA at low concentration ranges (<3.0 mg L(-1)) enhanced cyprodinil photodegradation while the photocatalytic rate was weakened with more addition of HA. The degradation rate in alkaline solutions was greater than in acidic solutions. Six main transformation products (TPs) were separated and identified based on mass spectra data and density functional theory (DFT) quantum calculations, and their kinetic evolutions were also investigated. Ultimately, a tentative transformation mechanism was proposed based the identified TPs and their kinetic evolutions. The results indicated that one alpha-H on pyridine ring of cyprodinil was hydroxylated to form TPs 1. TPs 1 underwent a series of photochemical reactions involving ring-opening, addition of one H2O molecule and demethylation on three-member ring to form TPs 2, which was further hydroxylated on benzene ring to form TPs 6. TPs 3-5 were three isomers from Hofmann-Martius rearrangement of cyprodinil. These findings were of utmost importance for elucidating environmental fate of cyprodinil in aquatic ecosystem and further environmental risk evaluation. PMID- 27265401 TI - Homoeologue expression insights into the basis of growth heterosis at the intersection of ploidy and hybridity in Cyprinidae. AB - Hybridization and polyploidization are considered important driving forces that form new epigenetic regulations. To study the changing patterns of expression accompanying hybridization and polyploidization, we used RNA-seq and qRT-PCR to investigate global expression and homoeologue expression in diploid and tetraploid hybrids of Carassius auratus red var. (?) (R) and Cyprinus carpio (?) (C). By comparing the relative expression levels between the hybrids and their parents, we defined the expression level dominance (ELD) and homoeologue expression bias (HEB) in liver tissue. The results showed that polyploidization contributed to the conversion of homoeologue ELD. In addition, hybridization had more effect on the change in HEB than polyploidization, while polyploidization had more effect on the change of global gene expression than hybridization. Meanwhile, similar expression patterns were found in growth-related genes. The results suggested that hybridization and polyploidization result in differential degrees of maternal HEB in three tissues (liver, muscle and ovary) tested. The results of this study will increase our understanding of the underlying regulation mechanism of rapid growth in diploid hybrids and allotetraploids. The differential degrees of global expression and homoeologue expression contribute to growth heterosis in newly formed hybrids, ensuring the on-going success of allotetraploid speciation. PMID- 27265403 TI - Pseudobacter ginsenosidimutans gen. nov., sp. nov., isolated from ginseng cultivating soil. AB - A Gram-stain-negative, pseudo-rod, non-spore-forming, oxidase- and catalase positive, strictly aerobic bacterium, designated Gsoil 221T, was isolated from soil of a ginseng field and subjected to a taxonomic analysis using a polyphasic approach. Strain Gsoil 221T grew at 10-37 degrees C and at pH 5.0-8.0 on R2A medium. Strain Gsoil 221T possessed beta-glucosidase activity, which was responsible for its ability to transform ginsenosides Rb1 and Rc (two dominant active components of ginseng) to ginsenoside F2. Phylogenetic study based on the 16S rRNA gene sequence positioned strain Gsoil 221T in a distinct lineage in the family Chitinophagaceae, sharing less than 94.4 % 16S rRNA gene sequence similarity with all taxa with validly published names. The strain showed the highest sequence similarities with members of the genera Parasegetibacter,Flavitalea,Niastella and Terrimonas. Strain Gsoil 221T contained MK-7 as predominant quinone, and iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G as major fatty acids. The DNA G+C content was 47.1 mol%. Strain Gsoil 221T could be distinguished from the other members of the family Chitinophagaceae by a number of chemotaxonomic and phenotypic characteristics. The major polar lipids of strain Gsoil 221T were diphosphatidylglycerol, phosphatidylethanolamine and one unidentified polar lipid. Based on these combined data, strain Gsoil 221T represents a novel species of a new genus in the family Chitinophagaceae, for which the name Pseudobacter ginsenosidimutans gen. nov., sp. nov. is proposed. The type strain of the type species is Gsoil 221T (=KACC 14278T=DSM 18116T). PMID- 27265402 TI - Fermi level position, Coulomb gap, and Dresselhaus splitting in (Ga,Mn)As. AB - Carrier-induced nature of ferromagnetism in a ferromagnetic semiconductor, (Ga,Mn)As, offers a great opportunity to observe novel spin-related phenomena as well as to demonstrate new functionalities of spintronic devices. Here, we report on low-temperature angle-resolved photoemission studies of the valence band in this model compound. By a direct determination of the distance of the split-off band to the Fermi energy EF we conclude that EF is located within the heavy/light hole band. However, the bands are strongly perturbed by disorder and disorder induced carrier correlations that lead to the Coulomb gap at EF, which we resolve experimentally in a series of samples, and show that its depth and width enlarge when the Curie temperature decreases. Furthermore, we have detected surprising linear magnetic dichroism in photoemission spectra of the split-off band. By a quantitative theoretical analysis we demonstrate that it arises from the Dresselhaus-type spin-orbit term in zinc-blende crystals. The spectroscopic access to the magnitude of such asymmetric part of spin-orbit coupling is worthwhile, as they account for spin-orbit torque in spintronic devices of ferromagnets without inversion symmetry. PMID- 27265404 TI - A Retrospective Exploration of the Impact of the 'Angelina Jolie Effect' on the Single State-Wide Familial Cancer Program in Perth, Western Australia. AB - Global media has the power to influence the ways the public engage with health services. On May 14th 2013, Angelina Jolie published an article in the New York Times magazine, outlining her decision to undergo BRCA mutation testing due to a family history of cancer; then proceed with a mastectomy. The article evoked significant interest from the media and the public. During the months that followed, the Familial Cancer Program (FCP) at Genetic Services of Western Australia (GSWA) experienced a significant increase in referrals and enquiries. Resources were overstretched and it became clear we needed to adjust work practices to manage the escalating numbers. New strategies were devised to cope with the influx of enquiries, albeit without the benefit of additional resources. We conducted an audit of referrals to the FCP made between January 2012 and December 2014. This included a comparison of the months prior to and following the New York Times article. The aim of the audit was to quantify the impact of the "Angelina Jolie effect" on referrals to the FCP. Whilst the increased awareness of the role of genetic services in risk assessment and testing for familial breast and ovarian cancer was considered positive, pre-referral risk assessment at the primary health level to evaluate the appropriateness of their patients for referral could have been helpful. Potentially, many inappropriate referrals to FCP may have been avoided with primary health evaluation thus lessening the burden on our service and preventing unnecessary worry in well women who possessed minimal family history or risk factors. It is important to understand the factors driving the uptake of risk reduction activities, particularly if engagement with a genetics service is considered part of that pathway. Continued education about cancer risk due to family history, individual features and awareness surrounding genetic testing criteria, costs and availability is required for both the public and health professionals. PMID- 27265405 TI - Predispositions to Lymphoma: A Practical Review for Genetic Counselors. AB - This review provides a synopsis for genetic counselors of the major concepts of lymphoma predisposition: genomic instability, immune deficiency, inappropriate lymphoproliferation, and chronic antigen stimulation. We discuss syndromes typifying each of these mechanisms. Importantly, our review of the genetic counseling literature reveals sparse discussion of genetically-based immune mediated lymphoma predisposition, which we address in depth here. We aim to increase awareness among genetic counselors and colleagues in oncology about familial susceptibility and facilitate critical thinking about lymphoma risk assessment. Clinical application of this knowledge is aided by recommendations for collection of personal and family history to guide risk assessment and testing. Lastly, we include a special discussion of genetic counseling issues including perceptions of the context, nature, and magnitude of lymphoma risk, as well as coping with awareness of susceptibility to lymphoma. PMID- 27265407 TI - Drug-resistant epilepsy in adults: Outcome trajectories after failure of two medications. AB - OBJECTIVE: To examine the seizure trajectories of adults with epilepsy developing drug-resistant epilepsy (DRE) and to identify the predictors of seizure trajectory outcome. METHODS: Adult patients failing two antiepileptic drugs (AEDs) due to inefficacy and starting their third AED at a tertiary epilepsy center were followed for seizure trajectory outcome during medical management. Seizure trajectories were categorized into one of four patterns: (1) course with constant seizures; (2) fluctuating course; (3) delayed attainment of seizure freedom (seizure freedom delayed for >12 months after start of the study, but patient stayed in seizure freedom); and (4) early attainment of seizure freedom (within 12 months of starting study). Multiple ordinal logistic regression models were used to estimate the association between trajectory categories and clinical factors. RESULTS: Four hundred three adult patients met the eligibility criteria. Of these, 212 (53%) never achieved a seizure-free period of a year or more. The trajectories of 63 patients (16%) had a complex fluctuating trajectory, 62 (15%) had delayed onset of seizure freedom, and 66 (16%) had an early seizure freedom. Independent predictors associated with more favorable outcome trajectories were epilepsy type and length of follow-up. Specifically, compared to patients with focal epilepsy of temporal lobe, patients with focal epilepsy of occipital lobe (OR 3.80, 95% confidence interval [CI] 1.00-14.51, p = 0.04), generalized genetic (OR 3.23, 95% CI 1.88-5.57, p < 0.0001), unclear epilepsy type (OR 3.82, 95% CI 1.53-9.52, p < 0.005), and both focal and generalized epilepsy(OR 11.73, 95% CI 1.69-81.34, p = 0.01) were significantly more likely to experience a better trajectory pattern. SIGNIFICANCE: Examination of patterns of seizure trajectory of patients with incident DRE showed that 31% were in continuous seizure freedom at the end of the observation period. PMID- 27265406 TI - Adherence to Recommended Risk Management among Unaffected Women with a BRCA Mutation. AB - Identifying unaffected women with a BRCA mutation can have a significant individual and population health impact on morbidity and mortality if these women adhere to guidelines for managing cancer risk. But, little is known about whether such women are adherent to current guidelines. We conducted telephone surveys of 97 unaffected BRCA mutation carriers who had genetic counseling at least one year prior to the survey to assess adherence to current guidelines, factors associated with adherence, and common reasons for performing and not performing recommended risk management. More than half of participants reported being adherent with current risk management recommendations for breast cancer (69 %, n = 67), ovarian cancer (82 %, n = 74) and both cancers (66 %, n = 64). Older age (OR = 10.53, p = 0.001), white race (OR = 8.93, p = 0.019), higher breast cancer genetics knowledge (OR = 1.67, p = 0.030), higher cancer-specific distress (OR = 1.07, p = 0.002) and higher physical functioning (OR = 1.09, p = 0.009) were significantly associated with adherence to recommended risk management for both cancers. Responses to open-ended questions about reasons for performing and not performing risk management behaviors indicated that participants recognized the clinical utility of these behaviors. Younger individuals and those with lower physical functioning may require targeted interventions to improve adherence, perhaps in the setting of long-term follow-up at a multi-disciplinary hereditary cancer clinic. PMID- 27265408 TI - Regulation of the Pacemaker Activity of Colonic Interstitial Cells of Cajal by Protease-Activated Receptors: Involvement of Hyperpolarization-Activated Cyclic Nucleotide Channels. AB - BACKGROUND AND PURPOSE: The exact mechanism of protease-activated receptors (PARs) on pacemaker activity of interstitial cells of Cajal (ICCs) has not been reported. We investigated the effects on pacemaker activity by the activation of PARs and its signal mechanisms in colonic ICCs. METHODS: The whole-cell patch clamp technique, RT-PCR and Ca2+ imaging were used in cultured ICCs from mouse colon. RESULTS: PAR-1 and PAR-2 were expressed in Ano-1 positive ICCs. TFLLR-NH2 (a PAR-1 agonist) and trypsin (a PAR-2 agonist) depolarized the membrane and increased the pacemaker potential frequency. U-73122 (a phospholipase C (PLC) inhibitor) and thapsigargin (a Ca2+ ATPase inhibitor) suppressed the TFLLR-NH2- and trypsin-induced effects on pacemaker potential. TFLLR-NH2 and trypsin also increased intracellular Ca2+ ([Ca2+]i) intensity with increasing of Ca2+ oscillations. Genistein (a tyrosine kinase inhibitor), SP600125 (a JNK inhibitor), CsCl, ZD7288, clonidine (hyperpolarization-activated cyclic nucleotide (HCN) channel blockers), SQ-22536 and dideoxyadenosine (adenylate cyclase inhibitors) suppressed the increased pacemaker potential frequency without effects on depolarization of the membrane induced by TFLLR-NH2 and trypsin. CONCLUSION: These results suggest that activation of PAR-1 and PAR-2 modulates the pacemaker activity of colonic ICCs through the PLC-dependent [Ca2+]i release pathway. The increased pacemaker potential frequency by PAR-1 and PAR-2 was also dependent on tyrosine kinase, JNK, and HCN activation. PMID- 27265418 TI - Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice. AB - The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future. PMID- 27265417 TI - Virtual unrolling and deciphering of Herculaneum papyri by X-ray phase-contrast tomography. AB - A collection of more than 1800 carbonized papyri, discovered in the Roman 'Villa dei Papiri' at Herculaneum is the unique classical library survived from antiquity. These papyri were charred during 79 A.D. Vesuvius eruption, a circumstance which providentially preserved them until now. This magnificent collection contains an impressive amount of treatises by Greek philosophers and, especially, Philodemus of Gadara, an Epicurean thinker of 1st century BC. We read many portions of text hidden inside carbonized Herculaneum papyri using enhanced X-ray phase-contrast tomography non-destructive technique and a new set of numerical algorithms for 'virtual-unrolling'. Our success lies in revealing the largest portion of Greek text ever detected so far inside unopened scrolls, with unprecedented spatial resolution and contrast, all without damaging these precious historical manuscripts. Parts of text have been decoded and the 'voice' of the Epicurean philosopher Philodemus is brought back again after 2000 years from Herculaneum papyri. PMID- 27265419 TI - Delayed activation of human microglial cells by high dose ionizing radiation. AB - Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation induced degenerative outcomes. We therefore investigated the effects of gamma irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 gamma rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of gamma rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1alpha, IL 10 and TNFalpha. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of gamma rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia. PMID- 27265420 TI - Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet alpha/beta cell ratio and subsequent insulin secretion. AB - Exogenous androgenic steroids applied to pregnant sheep programmes a PCOS-like phenotype in female offspring. Via ultrasound guidance we applied steroids directly to ovine fetuses at d62 and d82 of gestation, and examined fetal (day 90 gestation) and postnatal (11 months old) pancreatic structure and function. Of three classes of steroid agonists applied (androgen - Testosterone propionate (TP), estrogen - Diethystilbesterol (DES) and glucocorticoid - Dexamethasone (DEX)), only androgens (TP) caused altered pancreatic development. Beta cell numbers were significantly elevated in prenatally androgenised female fetuses (P = 0.03) (to approximately the higher numbers found in male fetuses), whereas alpha cell counts were unaffected, precipitating decreased alpha:beta cell ratios in the developing fetal pancreas (P = 0.001), sustained into adolescence (P = 0.0004). In adolescence basal insulin secretion was significantly higher in female offspring from androgen-excess pregnancies (P = 0.045), and an exaggerated, hyperinsulinaemic response to glucose challenge (P = 0.0007) observed, whereas prenatal DES or DEX treatment had no effects upon insulin secretion. Postnatal insulin secretion correlated with beta cell numbers (P = 0.03). We conclude that the pancreas is a primary locus of androgenic stimulation during development, giving rise to postnatal offspring whose pancreas secreted excess insulin due to excess beta cells in the presence of a normal number of alpha cells. PMID- 27265422 TI - Timing of First Sexual Intercourse and Young Adult Health Outcomes. AB - PURPOSE: To examine how age of onset of sexual intercourse is associated with past-year and lifetime sexually transmitted infections (STIs) and depression in young adulthood. METHODS: We examined how occurrence of a lifetime and past-year STI, lifetime diagnosis of depression, and past-week depressive symptoms differed as a function of age of onset of sexual intercourse using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health; N = 8,938 individuals). Time-varying effect models were used to examine how age of onset, measured as continuous age, was associated with these outcomes in young adulthood, with all analyses stratified to examine gender differences. RESULTS: Individuals who engaged in first intercourse before age 16 reported higher than average rates of all outcomes studied; for example, an estimated 35% of women and 12% of men who initiated at age 14 years reported a lifetime STI, compared with about 5% of those who initiated at age 24 years. Timing of first intercourse past the mid-twenties was associated with lower than average rates of STIs and lifetime depression diagnoses but was associated with a somewhat higher level of past-year depressive symptoms. Patterns were similar by gender, although there was little difference in men's depression diagnoses by age of onset. CONCLUSIONS: Results suggest that sexual intercourse before age 16 years may be associated with higher rates of STIs and depression. Findings provide support for comprehensive programs that both promote delay of first intercourse and provide safe sex and psychological support for those who initiate early. PMID- 27265421 TI - Gabapentin misuse, abuse and diversion: a systematic review. AB - BACKGROUND AND AIMS: Since its market release, gabapentin has been presumed to have no abuse potential and subsequently has been prescribed widely off-label, despite increasing reports of gabapentin misuse. This review estimates and describes the prevalence and effects of, motivations behind and risk factors for gabapentin misuse, abuse and diversion. METHODS: Databases were searched for peer reviewed papers demonstrating gabapentin misuse, characterized by taking a larger dosage than prescribed or taking gabapentin without a prescription, and diversion. All types of studies were considered; grey literature was excluded. Thirty-three papers met inclusion criteria, consisting of 23 case studies and 11 epidemiological reports. Published reports came from the United States, the United Kingdom, Germany, Finland, India, South Africa and France, and two analyzed websites not specific to a particular country. RESULTS: Prevalence of gabapentin misuse in the general population was reported to be 1%, 40-65% among individuals with prescriptions and between 15 and 22% within populations of people who abuse opioids. An array of subjective experiences reminiscent of opioids, benzodiazepines and psychedelics were reported over a range of doses, including those within clinical recommendations. Gabapentin was misused primarily for recreational purposes, self-medication or intentional self-harm and was misused alone or in combination with other substances, especially opioids, benzodiazepines and/or alcohol. Individuals with histories of drug abuse were most often involved in its misuse. CONCLUSIONS: Epidemiological and case report evidence suggests that the anti-epileptic and analgesic medication gabapentin is being misused internationally, with substance abuse populations at special risk for misuse/abuse. PMID- 27265423 TI - Evaluation of Bar and Nightclub Intervention to Decrease Young Adult Smoking in New Mexico. AB - PURPOSE: Over 20% of young adults in New Mexico currently smoke. We evaluated cigarette smoking prevalence of young adult bar patrons during an anti-tobacco Social Branding intervention. METHODS: The Social Branding intervention used a smoke-free brand, "HAVOC," to compete with tobacco marketing within the "Partier" young adult peer crowd. A series of cross-sectional surveys were collected from adults aged 18-26 in bars and nightclubs in Albuquerque, New Mexico, from 2009 to 2013 using randomized time-location sampling. Multivariable multinomial regression using full information maximum likelihood estimation to account for missing data evaluated differences in daily and nondaily smoking during the intervention, controlling for demographics, other risk behaviors, and tobacco related attitudes. RESULTS: Data were collected from 1,069 individuals at Time 1, and 720, 1,142, and 1,149 participants at Times 2, 3, and 4, respectively. Current smoking rates decreased from 47.5% at Time 1 to 37.5% at Time 4 (p < .001). Among Partiers, the odds of daily smoking decreased significantly, but nondaily smoking was unchanged. Partiers that recalled, liked, and understood the smoke-free message of HAVOC had lower odds of nondaily (odds ratio: .48, 95% CI: .31-.75) and daily (odds ratio: .31, 95% CI: .14-.68) smoking than those who did not recall HAVOC. HAVOC recall was associated with attitudes that were also associated with smoking behavior. CONCLUSIONS: The significant decrease in daily smoking among young adult Partiers in New Mexico was associated with HAVOC recall and understanding. Social Branding interventions efficiently target and may decrease tobacco use among young adult bar patrons. PMID- 27265424 TI - Associations Between Parental and Grandparental Marijuana Use and Child Substance Use Norms in a Prospective, Three-Generation Study. AB - PURPOSE: Using prospective longitudinal data from three generations, this study seeks to test whether and how parent and grandparent marijuana use (current and prior) predicts an increased likelihood of child cigarette, alcohol, and marijuana use. METHODS: Using multilevel modeling of prospective data spanning three generations (n = 306 families, children ages 6-22), this study tested associations between grandparent (G1) and parent (G2) marijuana use and child (G3) past-year cigarette, alcohol, and marijuana use. Analyses tested whether G3 substance-related norms mediated these associations. Current G1 and G2 marijuana use was examined, as was G2 high school and early adult use and G1 marijuana use when G2 parents were in early adolescence. Controls included G2 age at G3 birth, G2 education and depression, and G3 gender. RESULTS: G2 current marijuana use predicted a higher likelihood of G3 alcohol and marijuana use but was not related to the probability of G3 cigarette use. G3's perceptions of their parents' norms and G2 current marijuana use both contributed independently to the likelihood of G3 alcohol and marijuana use when included in the same model. G3 children's own norms and their perceptions of friends' norms mediated the link between G2 current marijuana use and G3 alcohol and marijuana use. CONCLUSIONS: Results are discussed in light of the growing trend toward marijuana legalization. To the extent that parent marijuana use increases under legalization, we can expect more youth to use alcohol and marijuana and to have norms that favor substance use. PMID- 27265426 TI - Case of abscess caused by Mycobacterium massiliense associated with swimming. PMID- 27265425 TI - Impact of arsenic(V) on testicular oxidative stress and sperm functional attributes in Swiss albino mice. AB - The arsenic (As) is a multi system effector including reproduction. The present study examined the association of graded doses of As(V) on testicular microenvironment and sperm function in mice. Thirty-six adult male mice were randomly assigned to six groups (n = 6). Group A served as control without test chemical. The groups B, C, D, E, and F were administered graded doses of 10, 25, 50, 100, and 200 ppm As(V), respectively, through drinking water for 40 days. A dose-dependant significant (P < 0.05) decrements were observed in epididymal sperm kinematic attributes (progressive motility, rapid, fast progressive, VCL, VSL, VAP, LIN, STR, WOB and TYPE A (STR >80 %, ALH 2.5 MUm) by CASA), viability, plasma membrane functional integrity, and mitochondrial membrane potential which were associated with insignificant decrease in serum testosterone levels. The histoarchitectural studies of testes showed progressive loss of spermatozoa concentration in the seminiferous tubules as the As(V) dose increased. The mice exposed to As(V) had an increase in the As accumulation, protein carbonylation, and lipid peroxidation levels associated with alterations in SOD, CAT, and GST activities in the testes. In conclusion, higher doses of As(V) (more than 50 ppm) were found to be testicular toxicants which impaired semen quality by inducing oxidative stress in the testicular microenvironment. PMID- 27265427 TI - Impaired interhemispheric synchrony in Parkinson's disease with depression. AB - The alterations of interhemispheric resting-state functional connectivity (FC) in Parkinson's disease (PD) with depression remain unclear, so we aimed to explore the differences of interhemispheric FC between PD with and without depression. Twenty-one depressed PD (DPD) patients, 49 non-depressed PD (NDPD) patients and 50 matched healthy controls (HC) participated in this study. Resting-state functional magnetic resonance imaging (fMRI) data were analyzed with the voxel mirrored homotopic connectivity (VMHC) approach. The DPD patients showed lower VMHC values in the bilateral dorsolateral prefrontal cortex (DLPFC) and calcarine cortex compared to both NDPD and HC groups, and further receiver operating characteristic curves (ROC) analyses revealed that the VMHC in these two brain areas could be used as biomarkers to distinguish DPD from NDPD and from HC. The pooled PD patients (both DPD and NDPD) exhibited decreased VMHC in the bilateral putamen, middle occipital gyrus (MOG), postcentral gyrus (PoCG), paracentral lobule (PCL) and cerebellum posterior lobe when compared with HC. Decreased VMHC values within the DLPFC and calcarine cortex appeared to be unique features for DPD and might be used as potential neuroimaging markers to distinguish DPD patients from NDPD and HC groups. These findings may underlie the neural mechanisms of depression in PD. PMID- 27265428 TI - A gradient-free method for the purification of infective dengue virus for protein level investigations. AB - Dengue virus (DENV) is a mosquito-transmitted flavivirus that infects approximately 100 million people annually. Multi-day protocols for purification of DENV reduce the infective titer due to viral sensitivity to both temperature and pH. Herein we describe a 5-h protocol for the purification of all DENV serotypes, utilizing traditional gradient-free ultracentrifugation followed by selective virion precipitation. This protocol allows for the separation of DENV from contaminating proteins - including intact C6/36 densovirus, for the production of infective virus at high concentration for protein-level analysis. PMID- 27265429 TI - Mortality study of employees at a chemical manufacturing plant using administrative databases. AB - BACKGROUND: This study investigated mortality in a cohort of 1,988 male workers at a chemical manufacturing plant (1981-2011) and evaluated the quality of the results obtained using administrative databases. METHODS: Information about the workers was obtained from the archives of the Italian National Institute for Social Insurance. Vital status and causes of death were ascertained through record linkage with electronic archives and follow-up mailing. Regional reference rates were used to calculate standardized mortality ratios (SMRs) and 90% confidence intervals (CI). RESULTS: The analysis showed increased SMR for selected cancers of a priori interest: respiratory system (SMR: 126.8; 90%CI: 105 152), pleura (330.5; 90%CI 164-596), and non-Hodgkin lymphoma (196.1; 90%CI 102 342). CONCLUSIONS: The results indicate an effect of hazardous exposures among workers in this chemical manufacturing plant. Using administrative databases to construct historical cohorts is an efficient method in time and resources, for estimating the risk of mortality and generating hypotheses. Am. J. Ind. Med. 59:866-876, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27265430 TI - Exome sequencing identified a novel de novo OPA1 mutation in a consanguineous family presenting with optic atrophy. AB - Inherited optic neuropathies are a heterogeneous group of disorders characterized by mild to severe visual loss, colour vision deficit, central or paracentral visual field defects and optic disc pallor. Optic atrophies can be classified into isolated or non-syndromic and syndromic forms. While multiple modes of inheritance have been reported, autosomal dominant optic atrophy and mitochondrial inherited Leber's hereditary optic neuropathy are the most common forms. Optic atrophy type 1, caused by mutations in the OPA1 gene is believed to be the most common hereditary optic neuropathy, and most patients inherit a mutation from an affected parent. In this study we used whole-exome sequencing to investigate the genetic aetiology in a patient affected with isolated optic atrophy. Since the proband was the only affected individual in his extended family, and was a product of consanguineous marriage, homozygosity mapping followed by whole-exome sequencing were pursued. Exome results identified a novel de novo OPA1 mutation in the proband. We conclude, that though de novo OPA1 mutations are uncommon, testing of common optic atrophy-associated genes such as mitochondrial mutations and OPA1 gene sequencing should be performed first in single individuals presenting with optic neuropathy, even when dominant inheritance is not apparent. PMID- 27265431 TI - Oral health-related quality of life in patients on chronic haemodialysis and after kidney transplantation. AB - OBJECTIVES: The objective of the study was to evaluate oral health-related quality of life (OHRQoL) depending on dental and periodontal situation in patients on haemodialysis (HD) and after kidney transplantation (KTx) compared to healthy controls (HC). SUBJECTS AND METHODS: OHRQoL was assessed using the German short form of Oral Health Impact Profile (OHIP G14). Dental health was estimated using the decayed, missing and filled teeth index (DMF-T). Periodontal health was classified as healthy/mild or moderate/severe periodontitis. STATISTICAL ANALYSIS: Mann-Whitney U-test, Kruskal-Wallis test, chi-square test and Fisher's test. RESULTS: Eighty-seven HD patients, 39 KTx patients and 91 HC were included. Significant differences in DMF-T, D-T, M-T and F-T scores were identified between groups (P < 0.001). The prevalence of moderate/severe periodontitis was significantly higher in the HD and KTx group compared to HC (P = 0.002). Differences in OHIP G14 between groups were neither clinical relevant nor statistically significant (P = 0.199). A significant effect of DMF-T (P = 0.012), M-T (P < 0.001) and periodontitis (P = 0.023) on the OHIP G14 scores was identified only in HC. CONCLUSIONS: Improvement in dental care of HD and KTx patients is required. OHIP G14 values provide a subjectively considered low importance of oral health in HD and KTx patients, leading to need of motivation and sensitisation of these patients. PMID- 27265433 TI - Using PCR and Real-Time PCR (LightCycler) for Diagnosis and Follow up of Invasive Fungal Infections in Patients with Hematological Malignancies and Transplantation. AB - In modern medicine, for early diagnosis of infections, tests that have high specificity and sensitivity should be preferred. For this reason, especially for patients with hematological malignancies and transplantation, that have high mortality and morbidity ratios, some molecular biological techniques are coming into use today for differential diagnosis and follow up of invasive fungal infections. In the coming years it will become easier to early diagnose and also to plan optimal treatments, by using these techniques for diagnosis of fungal infections. In this study, we made fungal DNA isolation from blood samples, which were taken from patients, in immunodeficiency state, with hematological malignancies and transplantation. For polymerase chain reaction (PCR), we used universal fungal primers. By using real-time PCR samples from 20 patients, which were found positive by PCR, the amount of DNA was measured. In real-time PCR, we used Aspergillus colonies as our standard, and for this purpose, SDA petri dishes were incubated for 72 hours at 30 degrees C and; 101-106 cfu/mL serial dilutions were made by using hemocytometry. We performed DNA isolation and PCR from these dilutions. Fungal species specific products giving one band of 500 bp, were fixed in 2% agarose gel. We measured the DNA amounts by real-time PCR by using Sybr Green I. Standard dilution series and extraction samples were studied at the same time by real-time PCR. Measurement of the DNA quantities in the separate samples, one at the time of first day and the other after 15 days were interpreted by the LightCycler system. Results of real-time PCR in these two different samples were compared; it was noted that fungal DNA was increased in 5, decreased in 6 and equivalent in 9 patients. These findings showed that real-time PCR is a new, specific and a sensitive method among the other quantitative PCR systems. This method was also quicker than the other quantitative PCR systems. Currently, the investigators prefer this method because, it gives early idea about patient condition, for early diagnosis of infections and treatment patients who are under risk of some kind of infection, and for follow up treatment results. Additionally for diagnosis of fungal infections serial samples in PCR, together with other conventional diagnostic methods, should used. PMID- 27265432 TI - Key Provisions of the Patient Protection and Affordable Care Act (ACA): A Systematic Review and Presentation of Early Research Findings. AB - OBJECTIVES: To conduct a systematic literature review of selected major provisions of the Affordable Care Act (ACA) pertaining to expanded health insurance coverage. We present and synthesize research findings from the last 5 years regarding both the immediate and long-term effects of the ACA. We conclude with a summary and offer a research agenda for future studies. STUDY DESIGN: We identified relevant articles from peer-reviewed scholarly journals by performing a comprehensive search of major electronic databases. We also identified reports in the "gray literature" disseminated by government agencies and other organizations. PRINCIPAL FINDINGS: Overall, research shows that the ACA has substantially decreased the number of uninsured individuals through the dependent coverage provision, Medicaid expansion, health insurance exchanges, availability of subsidies, and other policy changes. Affordability of health insurance continues to be a concern for many people and disparities persist by geography, race/ethnicity, and income. Early evidence also indicates improvements in access to and affordability of health care. All of these changes are certain to ultimately impact state and federal budgets. CONCLUSIONS: The ACA will either directly or indirectly affect almost all Americans. As new and comprehensive data become available, more rigorous evaluations will provide further insights as to whether the ACA has been successful in achieving its goals. PMID- 27265434 TI - Therapeutic Trial of Cobalamin in Patients with Normal Serum Cobalamin Levels and Predicted Cobalamin Deficiency. AB - Diagnosis of cobalamin deficiency can be difficult due to the variation in clinical presentation and lack of specificity of the laboratory findings. Although hypersegmentation and macrocytosis are important findings observed in cobalamin deficiency they are not sensitive and spesific. Additionally, cobalamin assays in commercial laboratories, being not reliable, makes the diagnosis more difficult. The metabolite assays, such as the total homocysteine and methylmalonic acid are costly, which restricts their widespread routine use. Our aim was to find out problems in diagnosis of cobalamin deficiency in general practice, and establish a better and cost-effective decision strategy for the diagnosis of this common clinical entity. Fifty patients with the diagnosis of cobalamin deficiency were retrospectively evaluated with respect to diagnosis. Normal cobalamin levels were observed at presentation in eight (16%) patients. Reticulocyte crisis was observed in all patients on the seventh day of cobalamin replacement therapy and all hematological parameters returned to normal at the end of three months of treatment. In anemic patients with clinical and biochemical findings suggestive of megaloblastic anemia, even though serum cobalamin level is normal, a therapeutic trial of cobalamin is cost effective and prevents delay in diagnosis. PMID- 27265435 TI - C-Reactive Protein in the Follow-up and Estimation of Infections in Acute Leukemic Patients. AB - Fifty-five febrile neutropenic episodes were monitored by C-reactive protein (CRP) in 26 patients with acute leukemia. In nonfebrile period of patients, serum CRP level was 0.89 mg/dL (range 0.1-8.8 mg/dL) while it was found to be raised to 9.57 mg/dL (range 0.5-24.1 mg/dL) in the febrile group (p= 0.0001). Serum CRP level at the onset of fever was 9.25 mg/dL (range 0.1-16.2 mg/dL) in patients in whom fever was treated succesfully with antipseudomonal beta-lactam antibiotic and aminoglycoside therapy declined to normal levels (p= 0.01); 17.0 mg/dL (range 5.2-33.5 mg/dL) in patients still persisting fever with this combined therapy and so obtained vancomycin (p= 0.001); 16.6 mg/dL (range 0-38.7 mg/dL) in patients required amphotericin B in addition (p= 0.001). In the initial febrile episode; fever resolved at day 3.3 +/- 1.21 in patients with serum CRP value below 5 mg/dL; at day 4.42 +/- 1.88 in patients with serum CRP value between 10-15 mg/dL; at day 5.14 +/- 1.68 in patients with serum CRP value above 15 mg/dL. There was no statistical difference at the time of fever resolution among the first three groups. There was a remarkable difference between groups with CRP values below 5 mg/dL and above 15 mg/dL (p= 0.04). We conclude that determination of serum CRP level before and after infection in febrile neutropenic patients is useful for the follow-up and estimation of febrile neutropenic episode in acute leukemic patients. PMID- 27265436 TI - Anti-HTLV-I/II Seroprevalence in Healthy Blood Donors in Izmir, Turkey. AB - Human T-cell lymphotropic virus type I (HTLV-I) is the first human retrovirus to be associated with malignant disease-namely, adult T-cell leukemia/lymphoma. HTLV I has also been associated with several diseases. HTLV-I has a worldwide distribution with major endemic foci in the Caribbean and Southern Japan. HTLV-II is a closely related retrovirus that shares considerable genomic homology with HTLV-I but has not been proven to be a pathogen. Major routes of transmission are blood transfusion, breast milk and sexual activity. In this study, we examined the seroprevalance of HTLV-I/II among healthy blood donors attended to Ege University Hospital in Izmir. 913 healthy blood donors were examined for the presence of anti-HTLV-I/II antibody in their sera. Serum specimens were tested with an enzyme immunoassay (EIA) (Organon Teknika, Vironostika HTLV-I/II Microelisa System, Holland). All of the 913 healthy blood donors were seronegative with EIA. These findings indicate that screening of blood donors for HTLV I/II is not necessary at present time. PMID- 27265437 TI - Prevalence of Hepatitis G Virus in Blood Donors and Recipients. AB - We evaluated the prevalence of hepatitis G virus (HGV) infection in patients who had received multiple blood components and in blood donors and the possible coinfection with hepatitis C virus (HCV). Eighty patients who had received multiple blood components and 70 eligible blood donors, as controls were included in this study. HGV RNA was determined by reverse polymerase chain reaction in serum. HGV-RNA was detected in three (3.7%) of patients and in one (1.4%) of controls. Statistical analysis showed no difference between the groups (p> 0.05). HGV and HCV coinfection was not observed in both patient and control groups. Although the most important risk factor for HGV infection was found to be blood transfusions in various studies, this study showed that there is not significant relationship between blood components transfusion and HGV infection. PMID- 27265438 TI - Agranulocytosis: A Rare Complication of Infectious Mononucleosis and Recovery After IVIG Therapy. AB - A six-year-old boy was admitted with acute agranulocytosis four weeks after the onset of infectious mononucleosis. His bone marrow aspiration revealed maturation arrest of myeloid series. He was hospitalized for agranulocytosis and he was put on intravenous immunoglobulin (IVIG) (400 mg/kg/day) on the third day of hospitalization for two days. His white blood cell count increased to 4200/mm3 (1176 PMNL absolutely) on the fifth day. This may suggest that IVIG therapy may be effective for early recovery from agranulocytosis which is a very rare complication of infectious mononucleosis. PMID- 27265439 TI - Successful Treatment of Infection- Associated Hemophagocytic Syndrome with Intravenous Immunoglobulin. AB - Hemophagocytic syndrome is a rare disorder characterized by a group of clinical, laboratory and histopathological findings such as fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, and hemophagocytosis in the bone marrow, spleen, and lymph nodes. Hemophagocytic syndrome may occur as a primary or secondary disease. Primary type of hemophagocytic syndrome is also known as familial erythrophagocytic lymphohistiocytosis and secondary type is mostly associated with an viral infection and known as infection-associated hemophagocytic syndrome (IAHS). Rapid diagnosis is very important in these patients since suggested treatment strategies for the two types have been different and mortality rate is very high. In this report we present the clinical and laboratory findings and the outcome of two children with IAHS to emphasize the importance of early diagnosis and the effectiveness of intravenous immunoglobulin therapy in these patients. PMID- 27265440 TI - Anaplastic T-Cell Lymphoma Associated with Hemophagocytic Syndrome: A Case Report. AB - Hemophagocytic syndrome (HPS) is mostly associated with malignant and infectious diseases. The causes and prognosis of this clinical syndrome depend on the underlying disease. And also treatment of this disease must be arranged according to the underlying causes. While non-Hodgkin's lymphomas (NHL) associated with HPS has been frequently observed, anaplastic T-cell NHL associated with HPS has been rarely reported. In this article we report a case of Ki-1+ anaplastic T-cell lymphoma associated with HPS in a 16-year-old woman who presented with fever and lymphadenopathy. PMID- 27265441 TI - Hypereosinophilia as a Preclinical Sign of Tongue Squamous Cell Cancer in a Gastric Cancer Patient with Complete Remission. AB - Although parasitic infestations and allergic disorders are the most common causes of eosinophilia it may also occompany malignant diseases. Many studies suggested that eosinophilia is related to tumor dissemination or necrosis. We are presenting a case; 10 months after gastric carcinoma operation who had severe eosinophilia with bone marrow and skin infiltration that gave response to steroid therapy. After three months, tongue squamous cell carsinoma as a second malignancy occurred in our patient that the eosinophilia could be the preclinical sign of the second cancer. PMID- 27265442 TI - CLL and squamous cell cancer of the auricula. PMID- 27265443 TI - Blocking elevated VEGF-A attenuates non-vasculature Fragile X syndrome abnormalities. AB - Fragile X syndrome (FXS) is the most common form of inherited mental retardation. In exploring abnormalities associated with the syndrome, we have recently demonstrated abnormal vascular density in a FXS mouse model (Galvan and Galvez, ). One of the most prominent regulators of vascular growth is VEGF-A (Vascular Endothelial Growth Factor A), suggesting that FXS is associated with abnormal VEGF-A expression. In addition to its role in vascular regulation, VEGF-A also induces cellular changes such as increasing cell proliferation, and axonal and neurite outgrowth independent of its effects on vasculature. These VEGF-A induced cellular changes are consistent with FXS abnormalities such as increased axonal material, dendritic spine density, and cell proliferation. In support of these findings, the following study demonstrated that FXS mice exhibit increased expression of VEGF-A in brain. These studies suggest that increased VEGF-A expression in FXS is contributing to non-vascular FXS abnormalities. To explore the role of VEGF-A in mediating non-vascular FXS abnormalities, the monoclonal antibody Bevacizumab was used to block free VEGF-A. Bevacizumab treatment was found to decrease FXS Synapsin-1 expression, a presynaptic marker for synapse density, and reduce FXS testicle weight to control levels. Blocking VEGF-A also alleviated FXS abnormalities on novel object recognition, a test of cognitive performance. These findings demonstrate that VEGF-A is elevated in FXS brain and suggest that its expression promotes non-vascular FXS abnormalities. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 14-25, 2017. PMID- 27265444 TI - Advances in aptasensors for the detection of food contaminants. AB - Food safety is a global health objective, and foodborne diseases represent a major crisis in health. Techniques that are simple and suitable for fast screening to detect and identify pathogenic factors in the food chain are vital to ensure food safety. At present, a variety of analytical methods have been reported for the detection of pathogenic agents. Whereas the sensitivity of detection and quantification are still important challenges, we expect major advances from new assay formats and synthetic bio-recognition elements, such as aptamers. Owing to the specific folding capability of aptamers in the presence of an analyte, aptasensors have substantially and successfully been exploited for the detection of a wide range of small and large molecules (e.g., toxins, antibiotics, heavy metals, bacteria, viruses) at very low concentrations. Here, we review the use of aptasensors for the development of highly sensitive and affordable detection tools for food analysis. PMID- 27265445 TI - Consumption of sugar-sweetened beverages and its association with overweight among young children from China. AB - OBJECTIVE: To fully understand the sugar-sweetened beverage (SSB) consumption status among Chinese young children and to explore its association with weight gain. DESIGN: In this cross-sectional study, data on sociodemographic characteristics, SSB intake and weight/height were collected by means of face-to face interviews. The intake of SSB among young Chinese children in relation to their age, different characteristics and types of SSB consumed is described, and the association between SSB intake and BMI-for-age Z-score and overweight is explored. SETTING: Seven large cities and two villages in China. SUBJECTS: Nine hundred and forty-six healthy children, aged 3-7 years. RESULTS: The proportion of SSB intake among Chinese young children was 80.5 %; 3.4 % were daily consumers, 34.0 % (31.4 %) consumed at least once per week (month). The per capita and per consumer SSB intake was 63.1 9 (sd 100.8) and 78.4 (sd 106.9) ml/d. Children from rural areas consumed twice, or even triple, the amount of SSB as those from urban areas (P<0.001) and great disparities existed between the types of SSB consumed by urban and rural children. An association was found between increased SSB intake and higher BMI-for-age Z-score (P<0.05) after adjusting for potential confounders; there was also an association between SSB intake and increased risk of being overweight or obese. CONCLUSIONS: The consumption status of SSB in Chinese young children is of concern. There was a positive association between SSB intake and weight gain. Measures should be taken to improve the present situation of SSB consumption among Chinese young children. PMID- 27265446 TI - Synthesis, crystal structure and second-order nonlinear optical property of a novel pentanary selenide (K3I)[InB12(InSe4)3]. AB - A novel pentanary selenide (K3I)[InB12(InSe4)3] was obtained via a high temperature solid-state method. It crystallizes in the hexagonal space group P6322 which features an InSe4 tetrahedron consolidated B12 icosahedron and 1-D chain constructed by InSe6 octahedron and B12Se12 cluster alternatively connected along the c-axis. Second-order nonlinear optical property measurement shows that it is second harmonic generation-active. Theory calculation indicates that it is an indirect semiconductor with the energy gap of 1.15 eV. PMID- 27265447 TI - Influenza vaccine effectiveness: Maintained protection throughout the duration of influenza seasons 2010-2011 through 2013-2014. AB - BACKGROUND: Factors, such as age, comorbidities, vaccine type, herd immunity, previous influenza exposure, and antigenic shift may impact the immune response to the influenza vaccine, protection against circulating strains, and antibody waning. Evaluating vaccine effectiveness (VE) is important for informing timing of vaccine administration and evaluating overall vaccine benefit. METHODS: VE was assessed using febrile respiratory illness surveillance among Department of Defense non-active duty beneficiaries from influenza seasons 2010-2011 through 2013-2014. Respiratory specimens were taken from participants meeting the case definition and tested by polymerase chain reaction for influenza. VE was calculated using logistic regression and by taking 1 minus the odds ratio of being vaccinated in the laboratory confirmed positive influenza cases versus laboratory confirmed negative controls. RESULTS: This study included 1486 participants. We found an overall adjusted VE that provided significant and fairly consistent protection ranging from 54% to 67% during 0-180days postvaccination. This VE dropped to -11% (95% confidence interval: -102% to 39%) during 181-365days. CONCLUSIONS: Our study found moderate VE up to 6months postvaccination. Since the influenza season starts at different times each year, optimal timing is difficult to predict. Consequently, early influenza vaccination may still offer the best overall protection. PMID- 27265448 TI - Pertussis vaccination during pregnancy: Antibody persistence in infants. AB - Maternal pertussis vaccination is associated with higher levels of pertussis antibodies at birth. We assessed the persistence of pertussis antibodies until primary vaccination in infants whose mothers received Tdap (tetanus, diphtheria, acellular pertussis) vaccine during pregnancy. Infants were born at the Hospital Clinic of Barcelona (Spain) in November 2014. Anti-PT IgG was determined by ELISA at delivery, between the first and second month of life, and estimated at 2months of age. The study included 37 infants whose mothers received Tdap between 21 and 38weeks of gestation. Infants presented a decline in GMC of anti-PT IgG between peripartum and follow-up levels, 52.7 (95% CI 34.7-80.2) versus 7.5 (95% CI 4.2 13.3) at 2months of age (p<0.001). The median half-life of maternal antibodies was 47days. More than half (51.4%) the infants presented detectable anti-PT IgG before the start of primary infant vaccination. PMID- 27265449 TI - Pneumococcal carriage in young children after introduction of PCV13 in Hong Kong. AB - OBJECTIVES: Pneumococcal conjugate vaccine (PCV) has been included in Hong Kong's Childhood Immunization Programme since 2009. This study aimed to assess nasopharyngeal pneumococcal carriage rate, serotypes and antimicrobial resistance pattern in young children after the introduction of 13-valent PCV (PCV13). STUDY DESIGN: A community-based, cross-sectional surveillance study was performed on healthy infants attending eleven Maternal and Child Health Centres across different parts of Hong Kong. Nasopharyngeal swabs were obtained from healthy children aged 2, 12 and 18months during their visit to the centers for immunization from June 2013 to June 2014. Pneumococcal isolates were serotyped and tested for antimicrobial resistance. Details of the demographics, family composition, vaccination history and medical history was obtained through interview of the guardians. RESULTS: 1541 children were recruited. The overall carriage rate was 5.5%. Children aged 12 and 18months were more likely to have pneumococcal colonization (12months OR: 2.88; 95% CI: 1.41-5.87 and 18months OR: 2.19, 95% CI: 1.05-4.57). Recent respiratory symptoms and presence of siblings younger than 6years were independently associated with pneumococcal carriage. Eighty-four pneumococcal isolates were serotyped. The most prevalent serogroup/types were 15 (15B/C, 16.7%; 15A/F, 9.5%), 6C (15.5%) and 23A (13.1%). Overall, 2.4% of the isolates were heptavalent PCV serotypes, 10.7% were PCV13 serotypes and 89.3% were non-PCV13 serotypes. The proportions of penicillin, cefotaxime and erythromycin non-susceptible isolates were 7.3%, 13.4% and 79.3% respectively. CONCLUSION: The rate of pneumococcal carriage was low in young children in Hong Kong and compared to previous local studies there appears to have been an overall reduction in the carriage rate after the introduction of PCV. Likely serotype replacement was noted with a predominance of non-vaccine serotypes in pneumococcal carriage with the emergence of serogroup/type 15 and 6C. PMID- 27265450 TI - Revaccination with 23-valent pneumococcal polysaccharide vaccine in the Japanese elderly is well tolerated and elicits immune responses. AB - BACKGROUND: Following primary vaccination of adults ?65years of age with 23 valent pneumococcal polysaccharide vaccine (PPSV23), immune responses increase and thereafter appear to decrease over time. With increased life expectancy worldwide, revaccination with PPSV23 may be required for continued protection of the elderly population against pneumococcal disease. The present study evaluated the immunogenicity and safety of revaccination with PPSV23 in the Japanese elderly. METHODS: Depending on prior history of PPSV23 vaccination, adults aged ?70years were given a first dose (primary group; N=81) or second dose (revaccination group; N=161, at least 5years after first dose) of PPSV23 intramuscularly. Subjects were matched for gender, age, and number and type of comorbidity across both groups. Blood samples were collected before and 4weeks postvaccination to measure serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic killing activity (OPA) antibody titers to serotypes included in the vaccine. Injection-site and systemic adverse events (AEs) were collected for 14days postvaccination. RESULTS: Baseline serotype specific IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) were generally higher in subjects with a prior history of PPSV23 vaccination than in PPSV23-naive subjects. The levels of IgG GMCs and OPA GMTs after revaccination were generally comparable to those observed after primary vaccination. Incidences of systemic AEs were comparable between the 2 groups. Although incidences of injection-site AEs were higher following revaccination than primary vaccination, the difference was not clinically significant as most AEs were mild to moderate in intensity and resolved within 5days after revaccination without treatment. CONCLUSION: Revaccination with PPSV23 was well tolerated and associated with increases in serotype-specific IgG concentrations and OPA titers in the elderly who received a prior PPSV23 dose at least 5years before. Revaccination with PPSV23 can be safely implemented in the elderly for continued prevention against pneumococcal disease. CLINICAL TRIAL REGISTRY NUMBER: NCT02260882. PMID- 27265451 TI - Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study. AB - BACKGROUND: Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged <1year. In Japan, PRP conjugated to tetanus toxoid (PRP-T) vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. METHODS: We compared the immunogenicity and safety of PRP conjugated to a non toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti PRP antibody titers ?1.0MUg/mL, after the primary series. RESULTS: Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non inferior to PRP-T vaccine (p<0.0001). Furthermore, the "short-term seroprotection rate" (anti-PRP antibody titer ?0.15MUg/mL) before booster vaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. CONCLUSION: The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. CLINICAL TRIAL REGISTRY: Registered on ClinicalTrials.gov: NCT01379846. PMID- 27265452 TI - Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria-Pertussis-Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP) - Immunological curiosity or canary in the mine? AB - BACKGROUND: Several previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification. METHODS: We have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent "bystander" IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens. RESULTS: We confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants. We additionally demonstrate that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this property. INTERPRETATION: Central to our interpretation of these findings are studies demonstrating: (i) mixed DTwP/DTaP priming improves resistance to pertussis disease and attenuates the IgE-stimulatory component of long term vaccine-specific memory; (ii) IgE mediated mechanisms can interfere with innate antiviral immunity and accordingly exacerbate airway symptoms in infected children. These observations, taken together with the data presented here, suggest a plausible mechanistic link between baseline pertussis-specific IgE titres in DTaP vaccinees and susceptibility to pertussis disease, which merits testing. Retrospective IgE analyses on sera collected from children at the time of presentation with pertussis could resolve this issue. PMID- 27265453 TI - High prevalence of active and occult hepatitis B virus infections in healthcare workers from two provinces of South Africa. AB - BACKGROUND: Hepatitis B (HB) is a vaccine-preventable liver disease caused by infection with the blood-borne hepatitis B virus (HBV). South African healthcare workers (HCWs) may be at high risk of occupational exposure to HBV infection, since previous studies have found suboptimal levels of protection against HBV in HCWs. METHODS: A descriptive prevalence study based on self-administered questionnaires with data on demographics and HB vaccination status, and stored serum samples collected from 2009 to 2012, from 333 HCWs working or studying in Gauteng and Mpumalanga province hospitals or nursing colleges, was conducted. Samples were tested for HB surface antigen (HBsAg), antibodies to HBsAg (anti HBs), antibodies to HB core antigen (anti-HBc), and HBV deoxyribonucleic acid (DNA). RESULTS: The majority of HCWs from whom the serum samples were drawn were black (91.4% [298/326]), female (82.6% [275/333]) and had received at least one dose of HB vaccine (70.9% [236/333]). The average age was 38.8years (range: 19 62). Of the HCWs, 23.2% (73/314) were susceptible (negative for all markers); 9.6% (30/314) were infected (HBsAg and/or DNA positive); 29.0% (91/314) were exposed (positive for either HBsAg, anti-HBc, or DNA); 18.8% (59/314) were immune due to natural infection (anti-HBs and anti-HBc positive only); while 47.8% (150/314) were immune due to vaccination (anti-HBs positive only). Furthermore, HBV DNA was detected in 8.6% (27/314) and occult HBV infection (OBI) (HBV DNA positive but HBsAg negative) was found in 6.7% (21/314) of samples. DISCUSSION AND CONCLUSION: This study, which is the first to report OBI in South African HCWs, found high rates of active HBV infection and sub-optimal protection against HBV in HCWs. There is a need to strengthen vaccination programmes through a policy that ensures protection for all HCWs and their patients. PMID- 27265454 TI - Pneumococcal vaccine impact on otitis media microbiology: A New Zealand cohort study before and after the introduction of PHiD-CV10 vaccine. AB - We compared the microbiology of middle ear fluid (MEF) in two cohorts of children having ventilation tube (VT) insertion; the first in the era of 7-valent Streptococcus pneumoniae conjugate vaccine (PCV7) and the second following introduction of the ten-valent pneumococcal vaccine (PHiD-CV10). METHODS: During 2011 (Phase 1) and again in 2014 (Phase 2) MEF and NP samples from 325 children and 319 children were taken at the time of VT insertion. A matched comparison group had NP swabs collected with 137 children (Phase 1) and 154 (Phase 2). Culture was performed on all NP and MEF samples with further molecular identification of Haemophilus species, serotyping of S. pneumoniae, and polymerase chain reaction (PCR) testing on all MEF samples. RESULTS: In Phase 2 immunisation coverage with ?3 doses of PHiD-CV10 was 93%. The rate and ratios of culture and molecular detection of the 3 main otopathogens was unchanged between Phase 1 and Phase 2 in both MEF and NP. Haemophilus influenzae was cultured in one quarter and detected by PCR in 53% of MEF samples in both time periods. S. pneumoniae and Moraxella catarrhalis were cultured in up to 13% and detected by PCR in 27% and 40% respectively of MEF samples. H. influenzae was the most common organism isolated from NP samples (61%) in the children undergoing VT surgery whilst M. catarrhalis (49%) was the most common in the non-otitis prone group. 19A was the most prominent S. pneumoniae serotype in both MEF and NP samples in Phase 2. Of Haemophilus isolates, 95% were confirmed to be non-typeable H. influenzae (NTHi) over both time periods. CONCLUSION: Following implementation of PHiD-CV10 in New Zealand, there has been no significant change in the 3 major otopathogens in NP or MEF in children with established ear disease. For these children non-typeable H. influenzae remains the dominant otopathogen detected. PMID- 27265455 TI - Sulfate-binding protein, CysP, is a candidate vaccine antigen of Moraxella catarrhalis. AB - Moraxella catarrhalis causes otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). A vaccine to prevent M. catarrhalis infections would have an enormous impact globally in preventing morbidity caused by M. catarrhalis in these populations. Using a genome mining approach we have identified a sulfate binding protein, CysP, of an ATP binding cassette (ABC) transporter system as a novel candidate vaccine antigen. CysP expresses epitopes on the bacterial surface and is highly conserved among strains. Immunization with CysP induces potentially protective immune responses in a murine pulmonary clearance model. In view of these features that indicate CysP is a promising vaccine antigen, we conducted further studies to elucidate its function. These studies demonstrated that CysP binds sulfate and thiosulfate ions, plays a nutritional role for the organism and functions in intracellular survival of M. catarrhalis in human respiratory epithelial cells. The observations that CysP has features of a vaccine antigen and also plays an important role in growth and survival of the organism indicate that CysP is an excellent candidate vaccine antigen to prevent M. catarrhalis otitis media and infections in adults with COPD. PMID- 27265456 TI - Probing vaccine antigens against bovine mastitis caused by Streptococcus uberis. AB - Streptococcus uberis is a worldwide pathogen that causes intramammary infections in dairy cattle. Because virulence factors determining the pathogenicity of S. uberis have not been clearly identified so far, a commercial vaccine is not yet available. Different S. uberis strains have the ability to form biofilm in vitro, although the association of this kind of growth with the development of mastitis is unknown. The objective of this study was to evaluate the potential use as vaccine antigens of proteins from S. uberis biofilms, previously identified by proteomic and immunological analyses. The capability of eliciting a protective immune response by targeted candidates was assayed on a murine model. Sera from rabbits immunized with S. uberis biofilm preparations and a convalescent cow intra-mammary infected with S. uberis were probed against cell wall proteins from biofilm and planktonic cells previously separated by two-dimensional gel electrophoresis. Using rabbit immunized serum, two proteins were found to be up regulated in biofilm cells as compared to planktonic cells; when serum from the convalescent cow was used, up to sixteen biofilm proteins were detected. From these proteins, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), fructose biphosphate aldolase (FBA), and elongation factor Ts (EFTs) were chosen to be tested as vaccine antigen candidates. For this purpose, different groups of mice were immunized with the three recombinant-expressed proteins (each one formulated separately in a vaccine), and thereafter intraperitoneally challenged with S. uberis. The three proteins induced specific IgG antibodies, but a significant reduction of mortality was only observed in the groups of mice vaccinated with FBA or EFTs. These results suggest that FBA and EFTs might be considered as strong antigenic candidates for a vaccine against S. uberis bovine mastitis. Moreover, this is the first study to indicate that also in S. uberis, GAPDH, FBA and EFTs, as proteins detected in both cytoplasm and cell wall fractions, can play a second function (moonlighting), the latter being particularly involved in the virulence of such a pathogen organism. PMID- 27265457 TI - Protective antibodies against a sphingomyelinase D from Loxosceles intermedia spider venom elicited in mice with different genetic background. AB - In the present investigation we used a recombinant LiD1 toxin, named rLiD1his, from Loxosceles intermedia brown spider to elicit specific antibodies in mice carrying different Human Leukocyte Antigens class II (HLAII) {DRB1.0401 (DR4), DQB1.0601 (DQ6) and DQB1.0302 (DQ8)} as well as in BALB/C and C57BL/6 control mice. All mice strains produced high antibody titers against rLiD1his but DR4 mice antibodies (the lower responder mice) were not able to recognize L. intermedia crude venom. The anti-rLiD1his sera, except from DR4 mice, were able to neutralize dermonecrotic, hemorrhagic and edematogenic effects of rLiD1his in naive rabbits. Overlapping peptides from the amino acid sequence of LiD1 toxin were prepared by SPOT method and differences in LiD1 epitope recognition were observed using different mice anti-rLiD1his sera. The region (160)DKVGHDFSGNDDISDVGK(177) was recognized by transgenic DQ8 and DQ6 mice sera. Other epitopes were recognized by at least two different animals' sera including (10)MGHMVNAIGQIDEFVNLG(27), (37)FDDNANPEYTYHGIP(51), (70)GLRSATTPGNSKYQEKLV(87) and (259)AAYKKKFRVATYDDN(273). Among these epitopes, the epitopes 37-51 and 160 177 have already been shown in previously studies as good candidates to be used alone or combined with other peptides to induce protective immune response against Loxosceles venoms. The results presented here highlight the importance of HLAII in antibody response and recognition of specific B-cell epitopes of rLiD1his spider toxin according to HLAII type and impact in the epitopic vaccine development against this spider. PMID- 27265458 TI - Development of a high-throughput beta-Gal-based neutralization assay for quantitation of herpes simplex virus-neutralizing antibodies in human samples. AB - Measurement of neutralizing antibodies against herpes simplex virus (HSV) is important for evaluation of candidate vaccines. The established plaque-reduction neutralization assay is time consuming, labor intensive, and difficult to validate and transfer. Here, we describe the characterization of a HSV neutralization assay based on the expression of a reporter gene, beta galactosidase (beta-Gal). Using previously constructed HSV-beta-Gal recombinant viruses, HSV-2/Gal and HSV-1/tk12, we developed a colorimetric beta-Gal-based neutralization assay that is sensitive and highly reproducible, and performed in less than 48h. HSV-1 and HSV-2 neutralizing titers measured by the beta-Gal-based neutralization assay were equivalent to those obtained by a plaque reduction neutralization assay. Intra- and inter-assay precision studies demonstrated that the beta-Gal-based assay was repeatable and yielded low and acceptable variation. In addition, comparison of HSV-2 neutralizing antibody (NAb) titers measured in two independent laboratories by two unique beta-Gal-based assays showed a highly significant correlation (r=0.9499, p<0.0001) between the two assays. The new assay will serve as an important tool both for preclinical and clinical trials of new HSV vaccines. PMID- 27265459 TI - Perceptions of oral cholera vaccine and reasons for full, partial and non acceptance during a humanitarian crisis in South Sudan. AB - Oral cholera vaccination (OCV) campaigns were conducted from February to April 2014 among internally displaced persons (IDPs) in the midst of a humanitarian crisis in Juba, South Sudan. IDPs were predominantly members of the Nuer ethnic group who had taken refuge in United Nations bases following the eruption of violence in December 2013. The OCV campaigns, which were conducted by United Nations and non-governmental organizations (NGOs) at the request of the Ministry of Health, reached an estimated 85-96% of the target population. As no previous studies on OCV acceptance have been conducted in the context of an on-going humanitarian crisis, semi-structured interviews were completed with 49 IDPs in the months after the campaigns to better understand perceptions of cholera and reasons for full, partial or non-acceptance of the OCV. Heightened fears of disease and political danger contributed to camp residents' perception of cholera as a serious illness and increased trust in United Nations and NGOs providing the vaccine to IDPs. Reasons for partial and non-acceptance of the vaccination included lack of time and fear of side effects, similar to reasons found in OCV campaigns in non-crisis settings. In addition, distrust in national institutions in a context of fears of ethnic persecution was an important reason for hesitancy and refusal. Other reasons included fear of taking the vaccine alongside other medication or with alcohol. The findings highlight the importance of considering the target populations' perceptions of institutions in the delivery of OCV interventions in humanitarian contexts. They also suggest a need for better communication about the vaccine, its side effects and interactions with other substances. PMID- 27265461 TI - The role of fusion activity of influenza A viruses in their biological properties. AB - Influenza A viruses (IAVs) cause acute respiratory infections of humans, which are repeated yearly. Human IAV infections are associated with significant morbidity and mortality and therefore they represent a serious health problem. All human IAV strains are originally derived from avian IAVs, which, after their adaptation to humans, can spread in the human population and cause pandemics with more or less severe course of the disease. Presently, however, the potential of avian IAV to infect humans and to cause the disease cannot be predicted. Many studies are therefore focused on factors influencing the virulence and pathogenicity of IAV viruses in a given host. The virus-host interaction starts by virus attachment via the envelope glycoprotein hemagglutinin (HA) to the receptors on the cell surface. In addition to receptor binding, HA mediates also the fusion of viral and endosomal membranes, which follows the virus endocytosis. The fusion potential of HA trimer, primed by proteolytic cleavage, is activated by low pH in endosomes, resulting in HA refolding into the fusion-active form. The HA conformation change is predetermined by its 3-D structure, is pH dependent, irreversible and strain-specific. The process of fusion activation of IAV hemagglutinin is crucial for virus entry into the cell and for the ability of the virus to replicate in the host. Here we discuss the known data about the characteristics of fusion activation of HA in relation to IAV virulence and pathogenicity. PMID- 27265460 TI - Phenotypes and Genotypes in Five Children with Congenital Insensitivity to Pain with Anhidrosis. AB - BACKGROUND: Congenital insensitivity to pain with anhidrosis is an extremely rare hereditary disorder linked to variants in NTRK1. Our goal was to characterize the clinical features and the genetic basis of the disorder in Chinese patients. METHODS: Patients were enrolled via social networking. Clinical features were investigated by interview, chart review, and physical examination. DNA was extracted from peripheral blood to genotype NTRK1 in patients and their parents. Variants identified were checked against a control cohort by high-throughput sequencing, and the effects of these variants were assessed in silico. RESULTS: Clinical features in five patients were cataloged, and six loss-of-function NTRK1 variants were identified, including a frameshift variant c.963delG, a nonsense variant c.1804C>T, an intron variant c.851-33T>A, and three missense variants c.1802T>G, c.2074C>T, and c.2311C>T. CONCLUSIONS: The results expand the spectrum of clinical and genetic features of congenital insensitivity to pain with anhidrosis and will help facilitate analysis of genotype-phenotype association in the future. PMID- 27265462 TI - Detection of emerging rotavirus G12P[8] in Sonora, Mexico. AB - Rotavirus is the most common cause of gastroenteritis in children up to five years of age worldwide. The aim of the present study was to analyze the genotypes of rotavirus strains isolated from children with gastroenteritis, after the introduction of the rotavirus vaccine in Mexico. Rotavirus was detected in 14/100 (14%) fecal samples from children with gastroenteritis, using a commercial test kit. The viral genome was purified from these samples and used as a template in RT-PCR amplification of the VP4 and VP7 genes, followed by gene cloning and sequencing. Among the rotavirus strains, 4/14 (28.5%) were characterized as G12P[8], 2/14 (14.3%), as G12P (not typed), and 3/14 (21.42%) as G (not typed) P[8]. Phylogenetic analysis of the VP7 gene showed that G12 genotypes clustered in lineage III. Phylogenetic analysis revealed that VP4 genotype P[8] sequences clustered in lineage V, whereas other P[8] sequences previously reported in Mexico (2005-2008) clustered in different lineages. Rotavirus genotype G12 is currently recognized as a globally emerging rotavirus. To our knowledge, this is the first report of this emerging rotavirus strain G12P[8] in Mexico. Ongoing surveillance is recommended to monitor the distribution of rotavirus genotypes and to continually reassess the suitability of currently available rotavirus vaccines. PMID- 27265463 TI - Development and application of ELISA for the detection of IgG antibodies to lymphocytic choriomeningitis virus. AB - Lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen, which can cause severe illnesses in humans. The most vulnerable are the human foetus and immunosuppressed individuals. Since there is no commercially available enzyme linked immunosorbent assay (ELISA) for the diagnosis of anti-LCMV antibodies in human sera, we developed a sandwich ELISA method detecting anti-nucleoprotein IgG antibodies, using a specific monoclonal anti-nucleoprotein antibody and cells persistently infected with LCMV strain MX as antigen. In the present study we show standardization of this ELISA protocol, determination of its clinical specificity and sensitivity and its application on 30 clinical samples from multiorgan donors. Comparison of these results to the indirect immunofluorescence antibody test (IFA) demonstrates that ELISA is more sensitive. The developed ELISA assay provides a fast, simple and efficient tool for the clinical detection of anti-nucleoprotein antibodies in human sera. PMID- 27265464 TI - Effect of the nucleotides surrounding the start codon on the translation of foot and-mouth disease virus RNA. AB - As for the alternative AUGs in foot-and-mouth disease virus (FMDV), nucleotide bias of the context flanking the AUG(2nd) could be used as a strong signal to initiate translation. To determine the role of the specific nucleotide context, dicistronic reporter constructs were engineered to contain different versions of nucleotide context linking between internal ribosome entry site (IRES) and downstream gene. The results indicate that under FMDV IRES-dependent mechanism, the nucleotide contexts flanking start codon can influence the translation initiation efficiencies. The most optimal sequences for both start codons have proved to be UUU AUG(1st) AAC and AAG AUG(2nd) GAA. PMID- 27265465 TI - Identification and characterization of two novel genomic RNA segments RNA5 and RNA6 in rose rosette virus infecting roses. AB - Rose rosette virus (RRV), a negative-strand RNA virus belonging to the genus Emaravirus, has recently been characterized to be the causal agent of rose rosette disease. Roses showing typical symptoms of RRV collected from a rose nursery in Florida were subjected to reverse transcription-PCR (RT-PCR) assay using primers corresponding to the conserved inverted 13 nucleotide long stretches found at the termini of the RRV genomic RNA segments. RT-PCR analysis yielded two novel genomic RNA segments, RNA5 and RNA6, in addition to the previously identified four RNA segments. The RNA5 is 1650 bp long and encodes for a polypeptide of 465 amino acids (54.3 K), while RNA6 is 1400 bp long and encodes for a polypeptide of 233 amino acids (27.05 K). RACE analysis showed that, both the RNA segments posses at their 5' and 3' termini, stretches of conserved inverted complementary13 nucleotides long sequence with two nucleotide mismatches as previously identified in other genomic RNA segments. Northern blot analysis as well as RT-PCR using specific primers showed the presence of the novel genomic RNA segments in infected plants, but absent in the non-infected plants. The GenBank Acc. Nos. for the sequences reported in this paper are KT007556 and KT007557. PMID- 27265466 TI - Characterization of two anti-dengue human monoclonal antibodies prepared from PBMCs of patients with dengue illness in Thailand. AB - The global spread of the four dengue virus (DENV) serotypes (dengue-1 to -4) has made this virus a major and growing public health concern. Generally, pre existing neutralizing antibodies derived from primary infection play a significant role in protecting against subsequent infection with the same serotype. By contrast, these pre-existing antibodies are believed to mediate a non-protective response to subsequent heterotypic DENV infections, leading to the onset of dengue illness. In this study, two monoclonal antibodies prepared by using peripheral blood mononuclear cells (PBMCs) from patients with dengue fever were characterized. Epitope mapping revealed that amino acid residues 254-278 in domain II of the viral envelope protein E were the target region of these antibodies. A database search revealed that certain sequences in this epitope region showed high conservation among the four serotypes of DENV. These two human monoclonal antibodies could neutralize DENV-2,-4 more effectively than DENV-1,-3. The amino acid sequences could not explain this difference in neutralizing activity. However, the 3D structure results showed that amino acid 274 could be the critical residue for the difference in neutralization. These results may provide basic information for the development of a dengue vaccine. PMID- 27265467 TI - Molecular characterization of a grapevine leafroll-associated virus 4 from Slovenian vineyards. AB - During a survey conducted in vineyards in Slovenia, variety of grapevine leafroll disease symptoms were observed. Mixed infection with grapevine leafroll associated viruses 3 and 4 (GLRaV-3, -4) in two grapevines from a vineyard in south-western part of Slovenia was confirmed by DAS-ELISA in 2010. The 3'final 1769 nucleotides of the Slovenian GLRaV-4 isolate were assembled from amplicons obtained by IC RT-PCR. The complete coat protein (CP) and p23 gene sequences were compared with other GLRaV-4 sequences from GenBank. Results showed that CP and p23 amino acid sequences of Slovenian variant (055-SI) are 88% and 85%, respectively, identical to corresponding genes of reference sequence GLRaV-4 LR106 (GenBank Acc. No. FJ467503). Phylogenetic analyses show that Slovenian variant clusters together with other corresponding strains of GLRaV-4. The sequencing results show great variability of the N-terminal part of the CP sequence indicating that this part of the genome is not suitable for molecular detection of the virus. To our knowledge this is also the first report of GLRaV-4 in Slovenian vineyards. PMID- 27265468 TI - Structure of transmembrane subunits gp47 of the foamy virus envelope glycoproteins. AB - The successful foamy viruses (FVs) infection includes at least two essential events, attachment to the cell surface and fusion of the viral envelope with the cell membrane. For the FVs, membrane fusion between virus and cell is mediated by envelope glycoprotein (Env) transmembrane (TM) subunit gp47. Compared with other retroviruses, FV TM subunit shares a similar but not identical structural characteristic. This paper focuses on in sillico analyses of all 15 available FV TM subunits gp47 based on their amino acid sequences. The hydrophobicity analysis revealed that the 15 FVs gp47 had two prominent hydrophobic regions, the N terminal fusion peptide (FP) and the C-terminal region, which included a membrane spanning domain (MSD) and a membrane proximal ectodomain region (MPER). In most FVs gp47, two heptad repeats, the coiled coils characterized by repetition of 7 amino acid-motif, were found to be correspondently located downstream of FP (named "N-HR") and the upstream of MPER (named "C-HR"). Furthermore, the solvent accessibility and secondary structure were predicted for all FVs gp47. These observations suggested that FVs gp47 possessed several fusion domains, which were necessary in the process of lipid membrane fusion between FVs and the target cells. PMID- 27265469 TI - Downregulation of SWI5 and CTC1 genes: hepatitis B virus DNA polymerase transactivated protein 1-mediated inhibition of DNA repair. AB - Hepatitis B virus (HBV) DNA polymerase transactivated protein 1 (HBVDNAPTP1) is a novel protein upregulated by HBV DNA polymerase, which has been screened by suppression subtractive hybridization technique (SSH) (GenBank Acc. No. AY450389). A vector pcDNA3.1 (-)/myc-His A-HBVDNAPTP1 was constructed and used to transfect acute monocytic leukemia cell line THP-1. HBVDNAPTP1 expression was detected by Western blot analysis in the cells. A cDNA library of genes downregulated by HBVDNAPTP1 in THP-1 cells was made in pGEM-T Easy using SSH. The cDNAs were sequenced and analyzed with BLAST search against the sequences in GenBank. Some sequences, such as DNA repair protein SWI5 homolog (SWI5) and CTS telomere maintenance complex component 1 (CTC1), might be involved in DNA repair. Protein expression of SWI5 and CTC1 was identified by Western blot in THP-1 cells. HBVDNAPTP1 could downregulate the expression of SWI5 and CTC1 at translation level. PMID- 27265470 TI - Detection of herbaceous-plant pararetrovirus in lichen herbarium samples. AB - Cauliflower mosaic virus (CaMV) - a plant pararetrovirus that naturally causes diseases in Brassicaceae and Solanaceae plant hosts worldwide - has been detected by PCR for the first time in herbarium samples of Usnea sp. lichens. The virus's presence in these lichens did not result in any micro- or macromorphological changes, and the herbarium records were classified as representative for the distinct species. Sequence analyses classified all the detected viruses into one lineage of CaMV isolates. We have shown here that herbarium samples could be a good source for virus study, especially where a longer time span is involved. PMID- 27265471 TI - Establishment and characterization of a chimeric infectious cDNA clone of classical swine fever virus. AB - Classical swine fever virus (CSFV) causes a highly contagious disease among swine that has an important economic impact worldwide. There are two important CSFV strains in China, Shimen and hog cholera lapinized virus (HCLV). Shimen strain is highly virulent while HCLV, also referred to as C-strain, is a live attenuated vaccine strain considered to be one of the most effective and safest live vaccines. In this study, a chimeric infectious cDNA clone of CSFV named pT7SM-c was engineered by replacing the E(rns) genomic region of an infectious clone of CSFV Shimen strain, pT7SM, with the same region obtained from HCLV. RNA transcripts of pT7SM-c containing an engineered EcoRI site that served as a genetic marker were directly infectious in PK15 cells. The rescued virus vT7SM-c showed similar growth kinetics and cytopathic effect with the parental virus vT7SM in the cells. The chimeric infectious cDNA clone can be used as a practical tool for further studying of the virulence, protein function and pathogenesis of CSFV through genetic manipulation. PMID- 27265472 TI - New way of purification of pathogenic rickettsiae reducing health risks. AB - In general, cultivation and purification of intracellular pathogenic rickettsiae represents a risk for laboratory personnel due to exposure to highly infectious aerosol or accidental inoculation during these procedures. In this study, we describe an alternative, effective and time saving technique for rickettsial purification using digitonin to release intracellular bacteria from host cell without physical disruption. No significant differences were noted in yield and infectivity between digitonin treated rickettsiae and rickettsiae purified by sonication. This is the first report of using digitonin in purification of pathogenic rickettsiae and this approach might be effective for other intracellular pathogenic bacteria. PMID- 27265473 TI - Expression of DOK1, 2, and 3 genes in HTLV-1-infected T cells. AB - Human T-cell leukemia virus type 1 (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATLL). The Tax protein encoded by the pX region of the HTLV-1 genome appears to be a key element in the early stage of ATLL development. In this study, we examined the expression of the downstream of tyrosine kinase (DOK) family members DOK1, DOK2 and DOK3, recently reported to be tumor suppressors, in HTLV-1-transformed T cells (MT-2 and HUT-102) and TL-Om1 cells derived from ATLL leukemic cells. DOK2 and DOK3 expression was significantly reduced in MT-2, HUT-102, and TL-Om1 cells compared with their expression in uninfected T cells, and the expression of DOK3 was reduced by the induction of Tax expression in T cells. PMID- 27265474 TI - Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast. AB - Phyllodes tumors (PT) are uncommon fibroepithelial breast neoplasms and there is currently no clear consensual treatment for these tumors. The aim of our study was to evaluate the surgical management and outcome of benign and borderline PT. We retrospectively assessed 76 cases of benign or borderline PT managed at the Leon Berard comprehensive cancer center in Lyon, France between July 2003 and December 2013. The mean age at diagnosis was 37.9 years and the median follow-up was 58 months. Seventy-five patients (99%), with a mean tumor size of 27 mm, underwent a breast-conserving procedure. The tumor margins were considered positive (when the tumor was present at the inked surgical section) in seven of 76 cases (9%) and negative in 65 out of 76 cases (86%). We observed the presence of small negative surgical margins <10 mm in 89% and <1 mm in 71% of the patients. Although no re-excision was performed to increase these margins, we did not see any increase in the local recurrence rate (4%) when compared to recurrence rates reported in the literature. We thus suggest that systematic revision surgery for close or positive surgical margins for benign PT should not be systematically performed. However, as recurrences occur within 2 years of initial excision, we recommend a regular clinical and imaging follow-up especially during this period for which patient's compliance is essential. PMID- 27265475 TI - Dynamics of a bacterial flagellum under reverse rotation. AB - To initiate tumbling of an E. coli, one of the helical flagella reverses its sense of rotation. It then transforms from its normal form first to the transient semicoiled state and subsequently to the curly-I state. The dynamics of polymorphism is effectively modeled by describing flagellar elasticity through an extended Kirchhoff free energy. However, the complete landscape of the free energy remains undetermined because the ground state energies of the polymorphic forms are not known. We investigate how variations in these ground state energies affect the dynamics of a reversely rotated flagellum of a swimming bacterium. We find that the flagellum exhibits a number of distinct dynamical states and comprehensively summarize them in a state diagram. As a result, we conclude that tuning the landscape of the extended Kirchhoff free energy alone cannot generate the intermediate full-length semicoiled state. However, our model suggests an ad hoc method to realize the sequence of polymorphic states as observed for a real bacterium. Since the elastic properties of bacterial flagella are similar, our findings can easily be extended to other peritrichous bacteria. PMID- 27265476 TI - Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo. AB - Non-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene specific up-regulation of endogenous functional proteins. PMID- 27265477 TI - Ethanol impedes embryo transport and impairs oviduct epithelium. AB - Most studies have demonstrated that alcohol consumption is associated with decreased fertility. The aim of this study was to investigate the effects of alcohol on pre-implantation embryo transport and/or early embryo development in the oviduct. We reported here that ethanol concentration-dependently suppressed the spontaneous motility of isolated human oviduct strips (EC50 50+/-6mM), which was largely attenuated in the present of L-NAME, a classical nitric oxide synthase(NOS) competitive inhibitor. Notably, either acute or chronic alcohol intake delayed egg transport and retarded early development of the embryo in the mouse oviduct, which was largely rescued by co-administration of L-NAME in a acute alcohol intake group but not in chronic alcohol intake group. It is worth mentioning that the oviductal epithelium destruction was verified by scanning electron microscope (SEM) observations in chronic alcohol intake group. In conclusion, alcohol intake delayed egg transport and retarded early development of the embryo in the oviduct by suppressing the spontaneous motility of oviduct and/or impairing oviductal epithelium. These findings suggested that alcohol abuse increases the incident of ectopic pregnancy. PMID- 27265478 TI - Oral pharmacokinetics and in-vitro metabolism of metyrapone in male rats. AB - OBJECTIVES: The purpose of this study was to investigate the pharmacokinetics of a single oral administration of metyrapone (MP) and metabolites produced from it in male Wistar rats, and the major tissues and enzymes involved in the production of the MP metabolites. Furthermore, the MP metabolism in human liver subcellular fractions was compared with that in rats. METHODS: High-performance liquid chromatography with ultraviolet detection (HPLC-UV) was used to determine the concentrations of MP and its metabolites in plasma and urine after administration, and the production activity of MP metabolites in subcellular fractions of various tissues. KEY FINDINGS: Plasma concentration of MP was rapidly increased and decreased, and the primary metabolite, metyrapol (MPOL), was immediately produced. The production activity of MPOL was substantially inhibited by an 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor in the rat and human liver microsomal and mitochondrial fractions. In the liver cytosolic fraction, the activity was inhibited by a carbonyl reductase inhibitor in the humans but not rats. CONCLUSIONS: In this study, we elucidated the plasma pharmacokinetics of MP and its metabolites in male rats after an oral administration. MPOL is most likely to be produced by 11beta-HSD1 in the male rats and humans. PMID- 27265479 TI - Autoimmune lymphoproliferative syndrome. PMID- 27265480 TI - The effect of imatinib mesylate on the erythroid colony formation from patients with polycythemia vera in the presence of different cytokines. AB - It has been shown that imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia, inhibits the effect of stem cell factor, which has a central role in erythropoiesis. In some polycythemia vera (PV) patients, it has inhibited autonomous erythroid colony growth in vitro and decreased the need for phlebotomy. In this study we have investigated the effect of insulin like growth factor (IGF)-I, stem cell factor (SCF) and erythropoietin (Epo) with interleukin (IL)-3, granulocyte macrophage-colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) in the presence of imatinib mesylate on the erythroid progenitors derived from peripheral blood mononuclear cells of three patients with PV and four healthy controls in semisolid medium. Erythroid colony formation from hematopoietic progenitors obtained from healthy controls was observed only in the presence of all cytokines. However, the number of erythroid colonies could not reach that of patients with PV. Inhibition of imatinib mesylate on erythroid colony growth was evident. Hematopoietic progenitors of patients with PV displayed two types of colony formation: the first type was exogenous cytokine-independent and was hypersensitive to current cytokines, and the second displayed hypersensitivity to current exogenous cytokines, but was exogenous cytokine-dependent. For both types, the inhibitory effect of imatinib mesylate was striking in the presence of all cytokines including IL-3, GM-CSF and Epo. There is no direct evidence yet that imatinib mesylate could inhibit the effect of IL-3, G-CSF, GM-CSF, Epo and IGF-I on erythropoiesis. Considering former studies together with results of this study, it can be argued that imatinib mesylate is effective in PV on the intersecting signal transduction mechanisms in which stem cell factor and its receptor may have a part. PMID- 27265481 TI - Hyperleukocytosis in childhood acute lymphoblastic leukemia: complications and treatment outcome. AB - Hyperleukocytosis, defined as a peripheral leukocyte count >= 100x109/L, is seen in 5-20% of newly diagnosed cases of childhood leukemia and is a poor prognostic factor. In this study, we aimed to examine the presenting clinical and laboratory features, complications, and treatment outcome of 47 children with acute lymphoblastic leukemia (ALL) and hyperleukocytosis who were diagnosed and treated in four medical centers of Izmir between January 1990 and January 2001. The median age was 5.0 years (range: 0.1-16.3 years). Median white blood cell count was 495x109/L (range: 107x109/L- 794x109/L). Forty-two of 47 patients (90%) had hepatosplenomegaly, 5 (11%) had respiratory distress, 3 (6%) had neurologic symptoms, 3 (6%) had diffuse cervical lymphadenopathy, and 3 (6%) had acute renal failure at admission. Ten of 47 patients (21%) had central nervous system involvement, and 17 (36%) had mediastinal mass. Ten patients (21%) had coagulopathy and 15 patients (32%) had metabolic complications (8 patients had hyperuricemia, 4 had hyperphosphatemia, 2 had hyperuricemia, hyperphosphatemia and hypercalcemia, and 1 had hypocalcemia) before the initiation of therapy. Forty of 47 patients (85%) with hyperleukocytosis were effectively managed with intravenous hydration, alkalinization, and allopurinol therapy. Early death during remission induction therapy occurred in 5 patients (11%) with respiratory distress and sepsis. Kaplan-Meier estimates of event free survival and overall survival were 37.0% and 40.5%, respectively. PMID- 27265482 TI - Does the history before blood transfusion identify donors who are glucose-6 phosphate dehydrogenase (G-6-PD) deficient? AB - The incidence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in Iran is around 10-14.9%. G-6-PD deficiency is an X-linked recessive disorder that is more prevalent in males. In our area, 80% of blood donors are males. At present, pre donation data are relied on for detecting diseases in Shiraz blood banks and the donors' blood is not routinely screened for G-6-PD deficiency. Transfusion of such blood may induce hemolysis in recipients, especially in premature neonates and in neonates having exchange transfusion. Four hundred and fifty blood bags in a blood bank of Shiraz from male donors were enrolled in this cross-sectional study. The blood samples were tested with fluorescent spot test for G-6-PD deficiency. G-6-PD-deficient donors were identified, and if they agreed, were asked to participate in the study. Each volunteer filled out a questionnaire. From 450 blood bags, 27 bags were G-6-PD deficient (6%). Only 19 donors could be traced who volunteered to participate in the study. Two donors (10%) had positive past history of hemolysis. Ten donors (52.6%) had positive family history of hemolysis (red urine and jaundice) when exposed to fava beans, mothballs, aspirin or other drugs. Nine donors had a male member in the family with hemolysis and one had a female relative with hemolysis. Five donors (26.3%) had positive history of neonatal jaundice. According to this study, 52% of donors had a positive family history of hemolysis, but only 10% had positive history of hemolysis themselves; therefore, addition of past history and family history of hemolysis has a good predictive value in detection of the G-6-PD-deficient donors. PMID- 27265483 TI - Molecular-cytogenetic aberrations in B-cell adult acute lymphoblastic leukemia (B ALL) - frequency and correlation with immunophenotype. AB - B-cell acute lymphoblastic leukemia (B-ALL) accounts for 20-30% of acute leukemias in adults. Combined application of data from immunophenotyping, karyotyping and molecular analyses allows a better understanding of this heterogeneous disease. We studied 30 adult patients with newly diagnosed B-ALL by conventional cytogenetics, fluorescent in situ hybridization (FISH) and immunophenotyping analyses. We report statistically significant prevalence of structural aberrations (43%) over numerical changes (17%) (p=0.02). The most frequent structural changes were t(9;22)(q34;q11)/bcr-abl-17%, t(8q24)/C-MYC-10%, t(11q23)/MLL-6%, del 4p-6%, del12p-3%, and t(1;19)-3%. Complex karyotype was found in 17% and normal karyotype in 30%. The most frequent immunophenotype was of common B-ALL (43%), and cytogenetic and/or molecular abnormalities were found in 78% of them. We distinguished a relatively high incidence (17%) of mature B ALL and 60% of them were associated with t(8;14)/C-MYC. We established association of cytogenetic aberrations with immunophenotype only in mature B-ALL. The other immunophenotypes are characterized by genetic heterogeneity and the presence of cytogenetic abnormalities unusual for adult B-ALL - trisomy 8 and t(1;19)(q23;p13). PMID- 27265484 TI - A retrospective study of clinico-hematological and cytogenetic profile of erythroleukemia from South India. AB - Objective of the study is the retrospective evaluation of clinico-hematological and cytogenetic profile of patients with erythroleukemia (EL) in a south Indian population. Case records of all patients with acute myeloid leukemia seen in the Department of Medical Oncology at Kidwai Memorial Institute of Oncology, Bangalore, between January 1997 and December 2004 were reviewed. Clinical details were noted and slides were reviewed. A total of 326 AML patient were diagnosed of whom 14 patients had AML M6. Contribution of EL to all forms of AML was 4.3%. The mean age was 37.1+13.9 yrs (range: 16-65); most patients were in their 4th decade, with a male: female ratio of 3.67: 1. Mean duration of symptoms in the present series was 10.9+6.9 weeks. Cytogenetics were normal in 71% of cases, and minor abnormalities were observed in 21% of cases. As a conclusion relative low incidence of secondary EL, more frequent normal karyotype, and relatively younger age observed in our series makes the picture of EL in our subcontinent different from that in other series reported thus far. PMID- 27265486 TI - Cryoglobulinemia as a cause of pseudoleukocytosis. PMID- 27265485 TI - Molecular identification of a rare hemoglobin variant, Hb J-Iran [beta77(EF1)His >Asp], in Denizli province of Turkey. AB - Hb J-Iran [beta77(EF1)His-Asp], a rare hemoglobin variant that does not present health problems, was reported for the first time in the Turkish population in 1986. Our case is the fourth case reported in Turkey and the first case from the Denizli province. PMID- 27265487 TI - Endothelial cell protein C receptor (EPCR) gene exon III, 23 BP insertion mutation in Turkish Cypriots. PMID- 27265488 TI - Effects of 10min vs. 20min passive rest after warm-up on 100m freestyle time trial performance: A randomized crossover study. AB - OBJECTIVES: The aim of this study was to compare the effect of 10min vs. 20min passive rest post warm-up on performance in a 100m freestyle time-trial. DESIGN: Randomized crossover. METHODS: Eleven competitive male swimmers performed two experimental trials on different days, consisting of 100m freestyle time-trials following 10min or 20min passive rest after a standard 1200m warm-up. Performance (time-trial), biomechanical (stroke length, stroke frequency, stroke index, propelling efficiency), physiological (blood lactate concentrations, heart rate, core and tympanic temperature), and psychophysiological (perceived effort) variables were assessed during both trials. RESULTS: Time-trial performance was faster after 10min as opposed to 20min passive rest (58.41+/-1.99s vs. 59.06+/ 1.86, p<0.01). This was supported by strong effect sizes (d=0.99) and the qualitative indication of "likely" positive effects. Heart rate before the time trial was also higher after 10min passive rest (89+/-12bpm vs. 82+/-13bpm; p<0.01). Furthermore, net core temperature and oxygen uptake values before the time-trial were substantially lower after 20min passive rest. CONCLUSIONS: These data suggest that the 10min post warm-up passive rest enhances 100m freestyle performance when compared to a 20min period. An improvement that appears to be mediated by the combined effects of a shorter post warm-up period on core temperature, heart rate and oxygen uptake. PMID- 27265489 TI - Traditional taxonomy: Quo vadis? PMID- 27265491 TI - Obituary Prof. Ernest Beutler (1928 - 2008). PMID- 27265492 TI - Fertility preservation in females with malignant disease-1: causes, clinical needs and indications. AB - Cancer incidence is progressively increasing in parallel with an increase in the rate of cancer survivors with the help of advanced treatment modalities. By the year 2010, it is estimated that one in every 250 persons will have survived a childhood malignancy. The increased rates of survival bring about complications related to reproductive health. Cytotoxic treatments due to chemo- and radiotherapy or bone marrow transplantation suppress or irreversibly harm not only female ovarian reserve but also male testicular sperm production. In this review, cryopreservation of gametes and gonads with fertility preservation options and indications prior to cancer treatments are discussed. PMID- 27265490 TI - Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk. AB - INTRODUCTION: Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify "optimal" candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. METHODS: Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify "optimal" candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring >=10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. RESULTS: Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were "optimal" candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3-2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2 2.3). The proportion of men who were "optimal" candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (>=26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP. CONCLUSIONS: A higher HIRI-MSM cut-off may be helpful for identifying candidates for PrEP scale-up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers. PMID- 27265493 TI - Ciprofloxacin: a novel therapeutic agent for iron overload? AB - OBJECTIVE: Major thalassemia is one of the hematological diseases requiring multiple blood transfusions, which results in iron overload in the liver, heart and other organs. Current iron chelation therapy consists of intravenous (IV) deferoxamine and oral deferasirox and deferiprone. Although these chelators are effective, many side effects are reported. In the present study, the iron chelating effect of ciprofloxacin with good oral absorption was investigated. METHODS: Thirty male albino Wistar rats were used for the study. Ciprofloxacin (7 or 14 mg/kg per day) was administered simultaneously with iron (0.03 g/kg per day) or after one-month administration of iron. Ciprofloxacin effect on iron absorption in the liver and heart was studied carefully using atomic absorption. RESULTS: A significant decrease in the liver and heart iron following the ciprofloxacin (14 mg/kg per day) administration was observed, when compared with the control group. This ciprofloxacin-induced tissue iron depletion was more pronounced when it was administered simultaneously with iron, when it was administered for a longer duration (2 months rather than 1 month) and when it was given in higher doses (14 mg/kg per day). CONCLUSION: Administration of ciprofloxacin may help to decrease the burden of parenteral administration, thereby improving compliance and also the life expectancy of thalassemic patients. PMID- 27265494 TI - Acute myeloid leukemia in Turkish children with Fanconi anemia. One center experience in the period between 1964-1995. AB - OBJECTIVE: Fanconi's anemia(FA) is an autosomal recessive disorder characterized by a progressive pancytopenia,variable congenital abnormalities and an increased risk for the development of acute myeloid leukemia (AML). The objective of this study is to evaluate AML in the patients with FA diagnosed and followed-up in the Department of Pediatric Hematology at Ankara University School of Medicine in the period between 1964-1995. METHODS: A total of 39 patients within the age range 2 14 years( mean 8.2+/-3.16),28 male and 11 female were diagnosed as FA on the basis of congenital abnormalities,pancytopenia, bone marrow hypoplasia and diepoxybutane induced chromosomal abnormalities that observed in all patients The hereditary and familial basis of FA was apparent in this series.Common abnormalities were growth retardation,cefe'- au- laitspots,hyperpigmentation,microcephaly, finger and thumb deformities,mental retardation and hypogenitalismus RESULTS: Four AML (10.2%) were observed in our series.Cytogenetic analysis of these cases revealed 46/ XX,dup(3)(q22;q26) t(7;17) (p11;p11) in one where it was unsuccessful in three.Two cases could not achieve remission and died.The other two achieved complete remission and remained in remission for2 and 6 months. CONCLUSION: Acute myelomonocytic type in three cases and acute monocytic type in one patient were diagnosed in our series. The patients with FA should be followed with regard to AML and solid tumors. AML and solid tomors should be taken into the consideration as the first manifestation of FA. PMID- 27265495 TI - Prevalence and etiological classification of thrombocytopenia among a group of pregnant women in Erbil City, Iraq. AB - OBJECTIVE: To determine prevalence and define causes of pregnancy associated thrombocytopenia METHODS: A total of 850 pregnant women at different ages of gestation were screened for thrombocytopenia. A control group of 150 age-matched nonpregnant women were tested for platelet count. Neoborns of thrombocytopenic women were tested within 24 hours of delivery and reassessment of women's platelets was done within 7-10 days post delivery. RESULTS: The mean platelet count in pregnant women was significantly lower than in nonpregnant women (221+/ 59.9 vs. 273+/-66.9). Thrombocytopenia affected 8% of cases, with peak incidence during the third trimester. Gestational thrombocytopenia was found to be the principal cause (73.8%); hypertensive disorders caused thrombocytopenia in 23% of cases and two cases (4%) were due to immune thrombocytopenic purpura. No maternal or fetal complications were noted. The mean platelet count of 51 neoborns of thrombocytopenic women was (240 +/- 7.1). Two neoborns (4%) had low platelet counts. CONCLUSION: Majority of thrombocytopenias were mild gestational and occurred in late in pregnancy. No maternal or neonatal bleeding complications were observed. PMID- 27265496 TI - Beta globin gene cluster haplotypes of the beta thalassemia mutations observed in Denizli province of Turkey. AB - OBJECTIVE: Our aim is to identify the beta globin gene cluster haplotypes for the beta thalassemia mutations in Turkey at regional basis. Beta thalassemia mutations included in this study were IVS-I-110 (G>A), FSC 8/9 (+G), IVS-II-1 (G>A), IVS-I-5 (G>C), IVS-I-1 (G>A), IVS-I-6 (T>C) and FSC 8 (-AA). METHODS: We studied 22 unrelated patients with beta-thalassemia major and 72 unrelated healthy subjects from our Department's DNA bank. Haplotype analysis was done by polymerase chain reaction (PCR)-based restriction enzyme digestion for the beta globin gene cluster of the following polymorphic restriction sites: Hinc II 5' to epsilon, Hind III 5' to Ggamma, Hind III in the IVS-II 5' to Agamma, Hinc II in pseudo beta, Hinc II 3' to pseudo beta, Ava II in beta, Hinf I 3' to beta. Associated haplotypes for the normal control samples (72 individuals, 144 chromosomes) were determined by Arlequin 3.1 software with unknown gametic phase. RESULTS: According to the results obtained, the most frequent beta globin gene cluster haplotypes in the normal population are (+----++), (+----+-), (-+-++++), (+-----+) with the frequencies of 28.6 %, 17.2 %, 9.8 % and 8.3 % respectively. IVS-I-110 mutation is linked with the haplotypes (+----++) and (+-----+). Observed haplotypes are (+----++) for FSC 8/9 (+G), (-+-+++-) for IVS-II-1 (G>A), (-+-++-+ and -+-++++) for IVS-I-5 (G>C), (+----+- and +------) for IVS-I-1 (G>A), (-++---+) for IVS-I-6 (T>C) and (+-----+) for FSC 8 (-AA). CONCLUSION: In conclusion, our region shows the Mediterranean character for the beta thalassemia mutations. According to the obtained results, IVS-I-110 (G>A) mutation linked with haplotype VII (+-----+), IVS-I-5 (G>C) mutation with haplotype IV (-+-++-+), codon 8/9 (+G) linked with haplotype I (+----++) were shown for the first time in Turkish population. The linkage of haplotype (+------) with the IVS-I-1 (G>A) mutation is reported for the first time in the published literature. In Denizli province of Turkey, beta globin gene cluster haplotypes of the normal population are strongly associated with the haplotypes of I (+----++), V (+----+-) and IX ( +-++++) respectively. PMID- 27265497 TI - Better differential diagnosis of iron deficiencyanemia from beta-thalassemia trait. AB - OBJECTIVE: Iron deficiency anemia (IDA) and beta- Thalassemia Trait (beta-TT) are the most common forms of microcytic anemia. This study was conducted to compare the validity of these discrimination indices in differentiating beta- Thalassemia Trait (beta-TT) from IDA by calculating their sensitivity, specificity and Youden's index. METHODS: Totally 323 subjects (173 children and 150 adult) with microcytic anemia were involved in this study. We calculated 10 discrimination indices in all patients with IDA and beta-TT. We divided the patients into two different groups as younger and older than 10 years. RESULTS: None of indices showed sensitivity and specificity of 100% in the patients older than 11 years, but only Shine and Lal Index showed sensitivity close to 90% and specificity of 100% in the patients younger than 10 years. The most accurate discriminative index for patients younger than 10 years was Shine & Lal and in case of patients older than 11 years it was RDWI. Youden's index for Shine & Lal & RBC Count and for RDWI & RBC Count indices has most diagnostic value for younger and older than 10 years, respectively. CONCLUSION: None of the indices was completely sensitive and specific in differentiation between beta-TT and IDA. MCHD mean and median were very close to normal values for both IDA and beta-TT patients, but in case of MHDL we have found mean and median were significantly higher than normal values in beta-TT and lower than those in IDA patients. In our study, Youden's index of RBC and S & L were the highest and the most reliable discrimination indices in differentiating beta-TT from IDA in the patients younger than 10 years and for patients older than 11 years, the most reliable discrimination indices were RBC and RDWI. PMID- 27265498 TI - Primary autoimmune myelofibrosis: a report of three cases and review of the literature. AB - Myelofibrosis in association with autoimmune disorders has been consistently recognized in sporadic case reports over a number of years. Autoimmune myelofibrosis has been described most commonly in association with systemic lupus erythematosus (SLE). In addition, myelofibrosis presenting as cytopenias and showing clinical response to immunosuppressant drugs, notably steroids, has been reported with a wide range of immune-mediated disorders, including Sjogren's syndrome, polyarteritis nodosa, rheumatoid arthritis, ulcerative colitis, and primary biliary cirrhosis. Attempts have been made to define a syndrome of primary autoimmune myelofibrosis (PAIMF), as a distinct steroid-responsive clinicopathologic entity with excellent prognosis. Herein, we describe three cases of autoimmune myelofibrosis with a review of the literature. PMID- 27265499 TI - Granulocytic sarcoma after stem cell transplantation in a child with biphenotypic leukemia. AB - Granulocytic sarcoma is an extramedullary tumor composed of leukemic blasts. Isolated granulocytic sarcoma has rarely been reported in children with leukemia undergoing allogeneic stem cell transplantation. We report a case of isolated granulocytic sarcoma arising from the pleura in an 11-year-old girl who was previously treated for biphenotypic leukemia with allogeneic stem cell transplantation. Complete resolution of the tumor was achieved after two inductions with MRC 12 protocol; however, she died of sepsis during the neutropenic period. The unusual presentation, immunophenotypic differences at diagnosis and relapse, and the management options are discussed. PMID- 27265500 TI - Hypertrichosis: the possible side effect of cyclosporin in an infant with hemophagocytic lymphohistiocytosis receiving HLH-2004 chemotherapy protocol. AB - Hemophagocytic lymphohistiocytosis is a life-threatening condition of severe hyperinflammation that results from an uncontrolled proliferation of activated lymphocytes and histiocytes secreting high amounts of inflammatory cytokines. The immediate treatment strategies include immune suppressive therapy such as corticosteriod, etaposide and cyclosporin A. Herein, we present a 13- month-old infant, who developed severe hypertrichosis after the administration of HLH-2004 treatment protocol and discuss the various hypotheses regarding the causal relationship between cyclosporine A and hypertrichosis, emphasizing the importance of patient follow up. PMID- 27265501 TI - Severe bone marrow aplasia and Coombs-positive autoimmune hemolytic anemia in microfilariasis - coincidental or causal? PMID- 27265502 TI - Depletion of innate immunity or bone marrow suppresion by viral infection ? PMID- 27265503 TI - Usage of U7 snRNA in gene therapy of hemoglobin S disorder - is it feasible? AB - OBJECTIVE: Hemoglobin (Hb) S disorder [beta6(A3)Glu-->Val, GAG-->GTG] is an important hemoglobinopathy with the highest endemicity in Africa. METHODS: Here, the author performs a basic bioinformatics gene ontology study to assess the effect of co-expression between nucleic acid sequence for human Hb S beta globin chain and U7.623. RESULTS: According to this study, the analytical results show that fully recovery of hemoglobin in both function and biological process can be got. CONCLUSION: Here, the author proposed that U7 snRNA might be a probable tool for treatment by gene therapy approach in Hb S disorder. PMID- 27265504 TI - CXCR2 Inhibition Profoundly Suppresses Metastases and Augments Immunotherapy in Pancreatic Ductal Adenocarcinoma. AB - CXCR2 has been suggested to have both tumor-promoting and tumor-suppressive properties. Here we show that CXCR2 signaling is upregulated in human pancreatic cancer, predominantly in neutrophil/myeloid-derived suppressor cells, but rarely in tumor cells. Genetic ablation or inhibition of CXCR2 abrogated metastasis, but only inhibition slowed tumorigenesis. Depletion of neutrophils/myeloid-derived suppressor cells also suppressed metastasis suggesting a key role for CXCR2 in establishing and maintaining the metastatic niche. Importantly, loss or inhibition of CXCR2 improved T cell entry, and combined inhibition of CXCR2 and PD1 in mice with established disease significantly extended survival. We show that CXCR2 signaling in the myeloid compartment can promote pancreatic tumorigenesis and is required for pancreatic cancer metastasis, making it an excellent therapeutic target. PMID- 27265505 TI - Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcgammaR Engagement. AB - While engagement of the inhibitory Fcgamma-receptor (FcgammaR) IIB is an absolute requirement for in vivo antitumor activity of agonistic mouse anti-CD40 monoclonal antibodies (mAbs), a similar requirement for human mAbs has been disputed. By using a mouse model humanized for its FcgammaRs and CD40, we revealed that FcgammaRIIB engagement is essential for the activity of human CD40 mAbs, while engagement of the activating FcgammaRIIA inhibits this activity. By engineering Fc variants with selective enhanced binding to FcgammaRIIB, but not to FcgammaRIIA, significantly improved antitumor immunity was observed. These findings highlight the necessity of optimizing the Fc domain for this class of therapeutic antibodies by using appropriate preclinical models that accurately reflect the unique affinities and cellular expression of human FcgammaR. PMID- 27265508 TI - Thermodynamics and kinetics of TopoII action: A consensus on T-segment curvature selection? Comment on "Disentangling DNA Molecules" by Alexander Vologodskii. PMID- 27265507 TI - Efficacy and safety of empagliflozin in patients with type 2 diabetes from Asian countries: pooled data from four phase III trials. AB - We investigated the efficacy and safety of empagliflozin over 24 weeks in Asian patients with type 2 diabetes (T2DM) using pooled data from four phase III trials. In these trials, patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo as monotherapy or add-on to metformin, metformin plus sulphonylurea or pioglitazone +/- metformin. In total, 1326 patients from Asia received >=1 dose of study drug. At week 24, adjusted mean differences versus placebo in change from baseline in glycated haemoglobin (HbA1c) were 0.66% [95% confidence interval (CI) -0.76, -0.56] and -0.73% (95% CI -0.83, 0.64) and in weight were -1.6 kg (95% CI -1.9, -1.3) and -1.8 kg (95% CI -2.1, 1.5) with empagliflozin 10 and 25 mg, respectively (all p < 0.001). Empagliflozin significantly reduced systolic and diastolic blood pressure. The proportion of patients reporting >=1 adverse event was similar across treatment groups, but events consistent with genital infection were more common in patients treated with empagliflozin 10 mg (3.4%) or 25 mg (2.3%) than placebo (0.9%). Thus in Asian patients with T2DM, empagliflozin reduced HbA1c, weight and blood pressure, and was well tolerated. PMID- 27265509 TI - Antiepileptic drug combinations not involving valproate and the risk of fetal malformations. AB - OBJECTIVE: To investigate the relationship between antiepileptic drug (AED) polytherapy in pregnant women and the risk of fetal malformations as prescribing practice changed, with valproate being used less often and at lower doses. Specifically, the risks associated with two of the most common AEDs included in polytherapy over recent years, levetiracetam and topiramate, were examined. METHODS: An observational cohort study in which malformation rates were analyzed in 1,461 pregnancies exposed to AED monotherapy, and in 484 exposed to antiepileptic drug combinations, from the Australian Register of Antiepileptic Drugs in Pregnancy over a 15-year period (1999-2014). RESULTS: Fetal malformation rates had fallen over time in monotherapy pregnancies, but increased in polytherapy pregnancies, despite decreasing use and lower dosages of valproate. The rise in polytherapy malformation rates began around 2005 when levetiracetam and topiramate use began to increase. Excluding pregnancies involving valproate exposure, malformation rates were higher in the remaining polytherapy pregnancies as compared with the monotherapy ones (6.90% vs. 3.64%; odds ratio [OR] 1.96, 95% confidence interval [CI] 1.14-3.39). Malformation rates were similar in polytherapy pregnancies whether or not levetiracetam was included (7.14% vs. 8.38%), but were higher in polytherapy pregnancies involving topiramate (14.94% vs. 6.55%: OR 2.507, 95% CI 1.23-5.10). Logistic regression showed that topiramate in polytherapy had a positive dose relationship with teratogenicity risk (p = 0.025). SIGNIFICANCE: The malformation risk associated with AED polytherapy depends on the specific drugs involved. Topiramate, when used as part of AED polytherapy that did not include valproate, was associated with a dose related increased risk of fetal malformations. PMID- 27265506 TI - ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma. AB - Activating mutations in Galphaq proteins, which form the alpha subunit of certain heterotrimeric G proteins, drive uveal melanoma oncogenesis by triggering multiple downstream signaling pathways, including PLC/PKC, Rho/Rac, and YAP. Here we show that the small GTPase ARF6 acts as a proximal node of oncogenic Galphaq signaling to induce all of these downstream pathways as well as beta-catenin signaling. ARF6 activates these diverse pathways through a common mechanism: the trafficking of GNAQ and beta-catenin from the plasma membrane to cytoplasmic vesicles and the nucleus, respectively. Blocking ARF6 with a small-molecule inhibitor reduces uveal melanoma cell proliferation and tumorigenesis in a mouse model, confirming the functional relevance of this pathway and suggesting a therapeutic strategy for Galpha-mediated diseases. PMID- 27265511 TI - Tuning the electronic properties and work functions of graphane/fully hydrogenated h-BN heterobilayers via heteronuclear dihydrogen bonding and electric field control. AB - Using density functional theory calculations with van der Waals correction, we show that the electronic properties (band gap and carrier mobility) and work functions of graphane/fully hydrogenated hexagonal boron nitride (G/fHBN) heterobilayers can be favorably tuned via heteronuclear dihydrogen bonding (C-HH B and C-HH-N) and an external electric field. Our results reveal that G/fHBN heterobilayers have different direct band gaps of ~1.2 eV and ~3.5 eV for C-HH-B and C-HH-N bonds, respectively. In particular, these band gaps can be effectively modulated by altering the direction and strength of the external electric field (E-field), and correspondingly exhibit a semiconductor-metal transition. The conformation and stability of G/fHBN heterobilayers show a strong dependence on the heteronuclear dihydrogen bonding. Fantastically, these bonds are stable enough under a considerable external E-field as compared with other van der Waals (vdW) 2D layered materials. The mobilities of G/fHBN heterobilayers we predicted are hole-dominated, reasonably high (improvable up to 200 cm(2) V(-1) s(-1)), and extremely isotropic. We also demonstrate that the work function of G/fHBN heterobilayers is very sensitive to the external E-field and is extremely low. These findings make G/fHBN heterobilayers very promising materials for field effect transistors and light-emitting devices, and inspire more efforts in the development of 2D material systems using weak interlayer interactions and electric field control. PMID- 27265510 TI - British Dietetic Association systematic review of systematic reviews and evidence based practice guidelines for the use of probiotics in the management of irritable bowel syndrome in adults (2016 update). AB - BACKGROUND: Probiotics are often taken by individuals with irritable bowel syndrome (IBS). Which products are effective is unclear, despite an increasing research base. This project will systematically review which strain- and dose- specific probiotics can be recommended to adults with IBS to improve symptoms and quality of life (QoL). It is part of a broader systematic review to update British Dietetic Association guidelines for the dietary management of IBS in adults. METHODS: CINAHL, Cochrane, Embase, Medline, Scopus and Web of Science were searched for systematic reviews (SRs) of randomised controlled trial (RCT)s recruiting adults with IBS comparing probiotic intervention with placebo. AMSTAR, risk of bias and diet bias tools were used to appraise methodological quality. Symptom and QoL data were appraised to develop probiotic-specific evidence statements on clinically meaningful and marginal outcomes in various settings, graded clinical practice recommendations and practical considerations. RESULTS: Nine systematic reviews and 35 RCTs were included (3406 participants) using 29 dose-specific probiotic formulations. None of the RCTs were at low risk of bias. Twelve out of 29 probiotics (41%) showed no symptom or QoL benefits. Evidence indicated that no strain or dose specific probiotic was consistently effective to improve any IBS symptoms or QoL. Two general clinical practice recommendations were made. CONCLUSIONS: Symptom outcomes for dose-specific probiotics were heterogeneous. Specific probiotic recommendations for IBS management in adults were not possible at this time. More data from high-quality RCTs treating specific symptom profiles are needed to support probiotic therapy in the management of IBS. PMID- 27265512 TI - Application of Monte Carlo simulation in addressing key issues of complex coacervation formed by polyelectrolytes and oppositely charged colloids. AB - This paper reviews the recent advance of Monte Carlo (MC) simulation in addressing key issues of complex coacervation between polyelectrolytes and oppositely charged colloids. Readers were first supplied with a brief overview of current knowledge and experimental strategies in the study of complex coacervation. In the next section, the general MC simulation procedures as well as representative strategies applied in complex coacervation were summarized. The unique contributions of MC simulation in either capturing delicate features, easing the experimental trials or proving the concept were then elucidated through the following aspects: i) identify phase boundary and decouple interaction contributions; ii) clarify composition distribution and internal structure; iii) predict the influences of physicochemical conditions on complex coacervation; iv) delineate the mechanisms for "binding on the wrong side of the isoelectric point". Finally, current challenges as well as prospects of MC simulation in complex coacervation are also discussed. The ultimate goal of this review is to provide readers with basic guideline for synergistic design of experiments in combination with MC simulation, and deliver convincing interpretation and reliable prediction for the structure and behavior in polyelectrolyte-macroion complex coacervation. PMID- 27265513 TI - Systematic understanding the mechanisms of vitiligo pathogenesis and its treatment by Qubaibabuqi formula. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Vitiligo is a depigmentation disorder, which results in substantial cosmetic disfigurement and poses a detriment to patients' physical as well as mental. Now the molecular pathogenesis of vitiligo still remains unclear, which leads to a daunting challenge for vitiligo therapy in modern medicine. Herbal medicines, characterized by multi-compound and multi target, have long been shown effective in treating vitiligo, but their molecular mechanisms of action also remain ambiguous. MATERIALS AND METHODS: Here we proposed a systems pharmacology approach using a clinically effective herb formula as a tool to detect the molecular pathogenesis of vitiligo. This study provided an integrative analysis of active chemicals, drug targets and interacting pathways of the Uygur medicine Qubaibabuqi formula for curing Vitiligo. RESULTS: The results show that 56 active ingredients of Qubaibabuqi interacting with 83 therapeutic proteins were identified. And Qubaibabuqi probably participate in immunomodulation, neuromodulation and keratinocytes apoptosis inhibition in treatment of vitiligo by a synergistic/cooperative way. CONCLUSIONS: The drug-target network-based analysis and pathway-based analysis can provide a new approach for understanding the pathogenesis of vitiligo and uncovering the molecular mechanisms of Qubaibabuqi, which will also facilitate the application of traditional Chinese herbs in modern medicine. PMID- 27265514 TI - Light-Induced Hydrogel Based on Tumor-Targeting Mesoporous Silica Nanoparticles as a Theranostic Platform for Sustained Cancer Treatment. AB - Herein, we report a facile fabrication of a polymer (azobenzene and alpha cyclodextrin-functionalized hyaluronic acid) and gold nanobipyramids (AuNBs) conjugated mesoporous silica nanoparticles (MSNs) to be used as an injectable drug delivery system for sustained cancer treatment. Because of the specific affinity between the hyaluronic acid (HA) on MSNs and the CD44 antigen overexpressed on tumor cells, the MSNs can selectively attach to tumor cells. The nanocomposite material then exploits thermoresponsive interactions between alpha cyclodextrin and azobenzene, and the photothermal properties of gold nanobipyramids, to in situ self-assemble into a hydrogel under near-infrared (NIR) radiation. Upon gelation, the drug (doxorubicin)-loaded MSNs carriers were enclosed in the HA network of the hydrogel, whereas further degradation of the HA in the hydrogel due to the upregulation of hyaluronidase (HAase) around the tumor tissue will result in the release of MSNs from the hydrogel, which can then be taken by tumor cells and deliver their drug to the cell nuclei. This design is able to provide a microenvironment with rich anticancer drugs in, and around, the tumor tissue for time periods long enough to prevent the recrudescence of the disease. The extra efficacy that this strategy affords builds upon the capabilities of conventional therapies. PMID- 27265515 TI - Common mycorrhizal networks amplify competition by preferential mineral nutrient allocation to large host plants. AB - Arbuscular mycorrhizal (AM) fungi interconnect plants in common mycorrhizal networks (CMNs) which can amplify competition among neighbors. Amplified competition might result from the fungi supplying mineral nutrients preferentially to hosts that abundantly provide fixed carbon, as suggested by research with organ-cultured roots. We examined whether CMNs supplied (15) N preferentially to large, nonshaded, whole plants. We conducted an intraspecific target-neighbor pot experiment with Andropogon gerardii and several AM fungi in intact, severed or prevented CMNs. Neighbors were supplied (15) N, and half of the target plants were shaded. Intact CMNs increased target dry weight (DW), intensified competition and increased size inequality. Shading decreased target weight, but shaded plants in intact CMNs had mycorrhizal colonization similar to that of sunlit plants. AM fungi in intact CMNs acquired (15) N from the substrate of neighbors and preferentially allocated it to sunlit, large, target plants. Sunlit, intact CMN, target plants acquired as much as 27% of their nitrogen from the vicinity of their neighbors, but shaded targets did not. These results suggest that AM fungi in CMNs preferentially provide mineral nutrients to those conspecific host individuals best able to provide them with fixed carbon or representing the strongest sinks, thereby potentially amplifying asymmetric competition below ground. PMID- 27265516 TI - Acute Fatal Alcohol Intoxication in a 3-Day-Old Neonate. PMID- 27265517 TI - "Eating" epilepsy revisited- an electro-clinico-radiological study. AB - This study aimed to evaluate the clinical, video electroencephalographic and MRI attributes of patients with eating epilepsy (EE). Consecutive patients who were diagnosed with EE and underwent potential pre-surgical work-up from 2003 to 2012 formed the study cohort. Their electro-clinico-radiological and seizure outcome data were obtained from our prospectively maintained medical records. Out of 7094 patients who underwent evaluation for refractory seizures, 47 patients satisfied the criteria for EE. Twenty-three (48.9%) had exclusive EE; the remainder had a combination of predominantly eating-induced and unprovoked seizures with no differences noted in timing of seizures in relation to meals. Lesional epilepsy was seen in 34% of patients, with posterior cortex (PC; posterior temporo-parieto occipital) predominance. In MRI negative patients, PC interictal epileptiform discharges were present in 34.4% of patients and multifocal in 20.6% of patients compared to the MRI positive group with 12.5% and 6.5%, respectively (p=0.003). Among 24 patients (51.1%) with co-existent unprovoked seizures, developmental delay and PC ictal onset was more prevalent (p=0.013 and 0.029) as compared to exclusive EE. The seizure frequency and outcome did not significantly differ between patients with or without MRI abnormality. Two patients underwent anterior temporal lobectomy, with persistence of their eating seizures postoperatively. EE is a complex reflex epilepsy of cryptogenic and symptomatic etiology. As opposed to the traditionally implied temporo-limbic mechanisms behind epileptogenesis, a multilobar network originating from the PC receiving sensory and visual inputs linked to the limbic-opercular pathways represents a plausible mechanism. Surgical selection should be diligent and cautious in this group of patients. PMID- 27265518 TI - Vibrational ladder-climbing in surface-enhanced, ultrafast infrared spectroscopy. AB - In a recent work (J. Phys. Chem. C 2016, 120, 3350-3359), we have introduced the concept of surface-enhanced, two-dimensional attenuated total reflectance (2D ATR IR) spectroscopy with modest enhancement factors (<50) using small plasmonic noble metal nanoparticles at solid-liquid interfaces. Here, we show that employment of almost continuous noble metal layers results in significantly stronger enhancement factors in 2D ATR IR signals (>450), which allows for multi quantum IR excitation of adsorbed molecules, a process known as "vibrational ladder-climbing", even for weakly absorbing (epsilon < 200 M(-1) cm(-1)) nitrile IR labels. We show that it is possible to deposit up to four quanta of vibrational energy in the respective functional group. Based on these results, optical near-fields of plasmonic nanostructures may pave the way for future investigations involving ultrafast dynamics of highly excited vibrational states or surface-sensitive coherent control experiments of ground-state reactions at solid-liquid interfaces. PMID- 27265519 TI - Characterization of the Key Aroma Volatile Compounds in Cranberry (Vaccinium macrocarpon Ait.) Using Gas Chromatography-Olfactometry (GC-O) and Odor Activity Value (OAV). AB - The volatile compounds of cranberries obtained from four cultivars (Early Black, Y1; Howes, Y2; Searles, Y3; and McFarlin, Y4) were analyzed by gas chromatography olfactometry (GC-O), gas chromatography-mass spectrometry (GC-MS), and GC-flame photometric detection (FPD). The result presented that a total of thirty-three, thirty-four, thirty-four, and thirty-six odor-active compounds were identified by GC-O in the Y1, Y2, Y3, and Y4, respectively. In addition, twenty-two, twenty two, thirty, and twenty-seven quantified compounds were demonstrated as important odorants according to odor activity values (OAVs > 1). Among these compounds, hexanal (OAV: 27-60), pentanal (OAV: 31-51), (E)-2-heptenal (OAV: 17-66), (E)-2 hexenal (OAV: 18-63), (E)-2-octenal (OAV: 10-28), (E)-2-nonenal (OAV: 8-77), ethyl 2-methylbutyrate (OAV: 10-33), beta-ionone (OAV: 8-73), 2-methylbutyric acid (OAV: 18-37), and octanal (OAV: 4-24) contributed greatly to the aroma of cranberry. Partial least-squares regression (PLSR) was used to process the mean data accumulated from sensory evaluation by the panelists, odor-active aroma compounds (OAVs > 1), and samples. Sample Y3 was highly correlated with the sensory descriptors "floral" and "fruity". Sample Y4 was greatly related to the sensory descriptors "mellow" and "green and grass". Finally, an aroma reconstitution (Model A) was prepared by mixing the odor-active aroma compounds (OAVs > 1) based on their measured concentrations in the Y1 sample, indicating that the aroma profile of the reconstitution was pretty similar to that of the original sample. PMID- 27265520 TI - Silencing of odorant binding protein gene AlinOBP4 by RNAi induces declining electrophysiological responses of Adelphocoris lineolatus to six semiochemicals. AB - Odorant binding proteins (OBPs) are believed to be important for transporting semiochemicals through the aqueous sensillar lymph to the olfactory receptor cells within the insect antennal sensilla. Here, we injected AlinOBP4-siRNA into the conjunctivum between prothorax and mesothorax of the lucerne plant bug, Adelphocoris lineolatus and evaluated the silencing of AlinOBP4 by reverse transcription polymerase chain reaction (RT-PCR) analysis, quantitative real-time PCR (qPCR) test and electroantennogram (EAG) assay. The combination of RT-PCR and qPCR analyses revealed that the levels of messenger RNA transcript were significantly reduced ~95% in AlinOBP4-siRNA-treated A. lineolatus males and ~75% in RNAi-treated females within 48 hours. It was found that there are different EAG responses between male and female bugs when the AlinOBP4 gene was silenced by RNAi. The EAGs of A. lineolatus to two plant volatiles, tridecanal and hexyl alcohol, were reduced 9.09% and 79.45% in RNAi-treated males, 62.08% and 62.08% in RNAi-treated females compared to the controls, separately. Antennae of RNAi treated bugs showed significantly lower electrophysiological responses to four sex pheromone analogs, butyl butanoate, 1-hexyl butyrate, (E)-2-hexenyl butyrate and hexyl hexanoate. The EAG recordings were reduced 35.43%, 35.24%, 39.96% and 78.47% in RNAi-treated males and 64.52%, 18.13%, 36.88% and 49.52% in RNAi treated females, respectively. The results suggested that AlinOBP4 might play dual-roles in the identification of plant volatiles and sex pheromones. It was suspected that AlinOBP4 may have different functions in odor perception between male and female A. lineolatus. PMID- 27265521 TI - Membrane-plate transition in leaves as an influence on dietary selectivity and tooth form. AB - Primates need accurate sensory signals about food quality to forage efficiently. Current evidence suggests that they target leaf foods based on color at long range, reinforcing this with post-ingestive sensations relating to leaf toughness evoked during chewing. Selection against tough leaves effectively selects against high fiber content, which in turn gives a greater opportunity of acquiring protein. Here we consider a novel intermediate mechanical factor that could aid a folivore: leaves may transform mechanically from membranes (sheets that cannot maintain their shape under gravitational loads and thus 'flop') early on in development into plates (that can maintain their shape) as they mature. This transformation can be detected visually. Mechanical tests on two species of leaf eaten by southern muriqui monkeys (Brachyteles arachnoides) in Southern Atlantic Forest, Brazil, support a membrane-to-plate shift in turgid leaves during their development. A measure of this mechanical transition, termed lambda (lambda), was found to correlate with both leaf color and toughness, thus supporting a potential role in leaf selection. Muriquis appear to select membranous leaves, but they also eat leaves that are plate-like. We attribute this to the degree of cresting of their molar teeth. A dietary choice restricted to membranous leaves might typify the type of 'fallback' leaf that even frugivorous primates will target because membranes of low toughness are relatively easily chewed. This may be relevant to the diets of hominins because these lack the bladed postcanine teeth seen in mammals with a specialized folivorous diet. We suggest that mammals with such dental adaptations can consume tougher leaf 'plates' than others. PMID- 27265522 TI - Microprofiling of nitrogen patches in paddy soil: Analysis of spatiotemporal nutrient heterogeneity at the microscale. AB - Flooded paddy soil ecosystems in the tropics support the cultivation of the majority of the world's leading crop, rice, and nitrogen (N) availability in the paddy-soil rooting zone limits rice production more than any other nutritional factor. Yet, little is known about the dynamic response of paddy soil to N fertiliser application, in terms of horizontal and vertical patchiness in N distribution and transformation. Here, we present a microscale analysis of the profile of ammonium (NH4(+)) and nitrate (NO3(-)), nitrification, oxygen (O2water and O2soil), and pH (pHwater and pHsoil) in paddy soils, collected from two representative rice-production areas in subtropical China. NH4(+) and NO3(-) exhibited dramatic spatiotemporal profiles within N patches on the microscale. We show that pHsoil became constant at 1.0-3.5 mm depth, and O2soil became undetectable at 1.7-4.0 mm. Fertiliser application significantly increased pH, and decreased O2, within N patches. Path analysis showed that the factors governing nitrification scaled in the order: pHwater > pHsoil > NH4(+) > O2water > NO3(-) > O2soil. We discuss the soil properties that decide the degree of nutrient patchiness within them and argue that such knowledge is critical to intelligent appraisals of nutrient-use efficiencies in the field. PMID- 27265523 TI - Clinical mass spectrometry proteomics (cMSP) for medical laboratory: What does the future hold? AB - BACKGROUND: Mass spectrometry (MS) methods are being widely used these days in medical laboratories for quantifying many small molecular analytes as well as for microbiological purposes. METHODS: Little use has been made so far, however, of MS for analyzing peptides and proteins in clinical laboratory (an approach known as clinical MS proteomics (cMSP)). The explanation for this situation may be that cMSP assays are more complex to implement than conventional assays, require large investments in terms of equipment and training, and have not yet been sufficiently validated for clinical applications. In addition, the protein analysis assays currently used in medical laboratories mostly meet both laboratory and clinical requirements in terms of analytical performances, ease of use, and turn-around-time. RESULTS: With the spread of MS methods in laboratories, increasing interest seems to be focusing on the development of MS for quantifying new analytes. MALDI-TOF MS methods have already been replacing classical methods of bacterial classification in clinical laboratories, for example, and this can be said to be an important step in this direction. CONCLUSIONS: In this paper, the literature available on the topic of clinical MS proteomics is reviewed and the pre-analytical, analytical, and post-analytical challenges which will have to be met in connection with this approach are discussed. PMID- 27265524 TI - A novel CDKL5 mutation in a Japanese patient with atypical Rett syndrome. AB - Rett syndrome (RTT) is a severe X-linked dominant inheritance disorder with a wide spectrum of clinical manifestations. Mutations in Methyl CpG binding protein 2 (MECP2), Cyclin dependent kinase-like 5 (CDKL5) and Forkhead box G1 (FOXG1) have been associated with classic and/or variant RTT. This study was conducted to identify the responsible gene(s) in atypical RTT patient, and to examine the effect of the mutation on protein function. DNA sequence analysis showed a novel heterozygous mutation in CDKL5 identified as c.530A>G which resulted in an amino acid substitution at position 177, from tyrosine to cysteine. Genotyping analysis indicated that the mutation was not merely a single nucleotide polymorphism (SNP). We also revealed that patient's blood lymphocytes had random X-chromosome inactivation (XCI) pattern. Further examination by bioinformatics analysis demonstrated the mutation caused damage or deleterious in its protein. In addition, we demonstrated in vitro kinase assay of mutant protein showed impairment of its activity. Taken together, the results suggested the mutant CDKL5 was responsible for the disease. PMID- 27265525 TI - Increased serum concentrations of signal peptide-Cub-Egf domain-containing protein-1 in patients with aneurysmal subarachnoid hemorrhage. AB - BACKGROUND: Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1), a marker for coagulation, is correlated with prognosis of some critical illnesses. The current study was designed to investigate the potential prognostic value of serum SCUBE1 concentrations in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Serum SCUBE1 concentrations of 125 patients and 125 controls were determined. Multivariate analyses were performed to identify independent risk factors for 6-month mortality, overall survival and unfavorable outcome (Glasgow Outcome Scale score of 1-3). RESULTS: Serum SCUBE1 concentrations were significantly higher in patients than in controls (17.7+/-7. vs. 1.2+/-0.4ng/ml, P<0.001) and were associated highly with World Federation of Neurological Surgeons (WFNS) scores (t=5.109, P<0.001) and modified Fisher scores (t=4.329, P<0.001). SCUBE1 emerged as an independent predictor for 6-month clinical outcomes. It had similar area under receiver operating characteristic curve (AUC) to WFNS scores and modified Fisher scores. Moreover, it could markedly improve the AUC of WFNS scores and modified Fisher scores to predict 6 month unfavorable outcome. CONCLUSION: Enhanced SCUBE1 concentrations are correlated with increasing severity and poor outcomes of aSAH patients, indicating SCUBE1 might have the potential to identify aSAH patients at risk of poor prognosis. PMID- 27265526 TI - Correlation detection as a general mechanism for multisensory integration. AB - The brain efficiently processes multisensory information by selectively combining related signals across the continuous stream of multisensory inputs. To do so, it needs to detect correlation, lag and synchrony across the senses; optimally integrate related information; and dynamically adapt to spatiotemporal conflicts across the senses. Here we show that all these aspects of multisensory perception can be jointly explained by postulating an elementary processing unit akin to the Hassenstein-Reichardt detector-a model originally developed for visual motion perception. This unit, termed the multisensory correlation detector (MCD), integrates related multisensory signals through a set of temporal filters followed by linear combination. Our model can tightly replicate human perception as measured in a series of empirical studies, both novel and previously published. MCDs provide a unified general theory of multisensory processing, which simultaneously explains a wide spectrum of phenomena with a simple, yet physiologically plausible model. PMID- 27265528 TI - Implications of expanded medicaid eligibility for patient outcomes after liver transplantation: Caveat emptor. PMID- 27265527 TI - Germ cell specific overactivation of WNT/betacatenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development. AB - All the major components of the WNT signalling pathway are expressed in female germ cells and embryos. However, their functional relevance in oocyte biology is currently unclear. We examined ovaries collected from TCFGFP mice, a well-known Wnt reporter mouse model, and found dynamic changes in the Wnt/betacatenin signalling activity during different stages of oocyte development and maturation. To understand the functional importance of Wnt signalling in oocytes, we developed a mouse model with the germ cell-specific constitutive activation of betacatenin using cre recombinase driven by the DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1(ex3)cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1(ex3)cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/betacatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth. PMID- 27265529 TI - Impact of rest breaks on musculoskeletal discomfort of Chikan embroiderers of West Bengal, India: a follow up field study. AB - OBJECTIVES: This study aimed to determine risk factors that predict musculoskeletal discomfort in Chikan embroiderers of West Bengal, India, and to compare the effect of two rest break schedules to reduce these symptoms. METHODS: The Nordic musculoskeletal questionnaire was performed on 400 Chikan embroiderers at baseline containing questions on job autonomy, working behavior, and work stress factors. Relative risk was calculated to identify prognostic factors for musculoskeletal discomfort in different body regions. Two groups of workers received two rest break schedules for 4 months and compared in a between-subject design. Outcome variables were scores of Body Part Discomfort (BPD) scale. RESULTS: Chikan embroiderers are afflicted with musculoskeletal discomfort mainly in the lower back, neck/shoulder and wrist/forearm region, which is attributed to their prolonged working timeinvolving hands and wrists, being in a static seating posture. Rigidity in working methods, prolonged working time, inadequate rest break during the working day, dissatisfaction regarding earning, monotonous work, static sitting posture, and repetitive movement of wrist and forearm were the significant predictors of these symptom developments. Rest break schedule 1 with more frequent and shorter breaks had more significant improvement on the severity of these musculoskeletal discomforts. CONCLUSIONS: Chikan embroiderers perform a highly dreary occupation and various ergonomics conditions work as predictors for developing musculoskeletal discomforts among them. Design of proper rest break schedule involving shorter and frequent breaks was competent for reducing these discomforts to a certain extent. PMID- 27265530 TI - Validity and reproducibility of self-reported working hours among Japanese male employees. AB - OBJECTIVE: Working long hours is a potential health hazard. Although self reporting of working hours in various time frames has been used in epidemiologic studies, its validity is unclear. The objective of this study was to examine the validity and reproducibility of self-reported working hours among Japanese male employees. METHODS: The participants were 164 male employees of four large-scale companies in Japan. For validity, the Spearman correlation between self-reported working hours in the second survey and the working hours recorded by the company was calculated for the following four time frames: daily working hours, monthly overtime working hours in the last month, average overtime working hours in the last 3 months, and the frequency of long working months (>=45 h/month) within the last 12 months. For reproducibility, the intraclass correlation between the first (September 2013) and second surveys (December 2013) was calculated for each of the four time frames. RESULTS: The Spearman correlations between self-reported working hours and those based on company records were 0.74, 0.81, 0.85, and 0.89 for daily, monthly, 3-monthly, and yearly time periods, respectively. The intraclass correlations for self-reported working hours between the two questionnaire surveys were 0.63, 0.66, 0.73, and 0.87 for the respective time frames. CONCLUSIONS: The results of the present study among Japanese male employees suggest that the validity of self-reported working hours is high for all four time frames, whereas the reproducibility is moderate to high. PMID- 27265531 TI - Comparison of biomarkers in serum and induced sputum of patients with occupational asthma and chronic obstructive pulmonary disease. AB - OBJECTIVES: Occupational asthma and chronic obstructive pulmonary disease (COPD) are associated with the airway inflammatory process. The aim of this study was to compare the sputum and serum markers of inflammation in patients with occupational asthma and COPD. METHODS: The study group included 20 patients with stable COPD, 24 patients with asthma, and 22 healthy subjects. Interleukin (IL) 6, IL-1beta, tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-9 levels in serum and induced sputum as well as fibrinogen and CRP in serum were determined in all the subjects. RESULTS: Higher concentrations of IL-1beta, IL-6, TNF-alpha, and MMP-9 in induced sputum and an increased concentration of acute phase proteins in serum were observed in COPD patients compared with healthy subjects. Higher concentrations of IL-1beta and MMP-9 in induced sputum and a higher concentration of C-reactive protein (CRP) were detected in COPD patients than in asthmatic subjects. Never smokers with COPD had significantly higher levels of IL-1beta and MMP-9 in induced sputum than never smoker controls. There was no significant difference between the serum and sputum levels of cytokines and MMP-9 of never smokers and smokers with COPD. CONCLUSIONS: Higher concentrations of IL-1beta and MMP-9 in induced sputum and a higher concentration of CRP in serum allow distinguishing between biomarker profiles of COPD patients and asthmatic patients. Occupational exposure induces a systemic proinflammatory state with increased levels of acute-phase proteins in stable COPD patients. MMP 9 and IL-1beta concentrations are increased in induced sputum of never smokers with COPD, which is associated with occupational exposure. PMID- 27265533 TI - Resilience, post-traumatic growth, and work engagement among health care professionals after the Great East Japan Earthquake: A 4-year prospective follow up study. AB - OBJECTIVES: Although attention has been paid to post-traumatic stress disorder (PTSD) among health care professionals after disasters, the impact of traumatic events on their work has not been elucidated. The aim of this study was to examine whether disaster-related distress, resilience, and post-traumatic growth (PTG) affect work engagement among health care professionals who had been deployed to the areas affected by the Great East Japan Earthquake that occurred on March 11, 2011. METHODS: We recruited disaster medical assistance team members who were engaged in rescue activities after the earthquake. The short version of the Resilience Scale (RS-14) and Peritraumatic Distress Inventory (PDI) were administered one month after the earthquake, and the short form of Posttraumatic Growth Inventory (SF-PTGI) and Utrecht Work Engagement Scale (UWES) were administered four years after the earthquake. Work engagement is composed of vigor, dedication, and absorption. Regression analyses were used to examine the relationship of UWES with RS-14, PDI, and SF-PTGI. RESULTS: We obtained baseline data of 254 participants in April 2011, and 191 (75.2%) completed the follow-up assessment between December 2014 and March 2015. The results showed that RS-14 predicted vigor, dedication, and absorption; in addition, SF-PTGI was positively related with these three parameters (p<0.01 for all). CONCLUSIONS: Resilience at baseline and PTG after rescue activities may increase work engagement among health care professionals after disasters. These findings could be useful for establishing a support system after rescue activities during a large-scale disaster and for managing work-related stress among health care professionals. PMID- 27265532 TI - Can leisure-time physical activity improve health checkup results? Evidence from Japanese occupational panel data. AB - OBJECTIVES: We examined the extent to which changes in worker health, as measured by health checkup items, were associated with increased intensity of leisure-time physical activity (LTPA) after controlling for individual time-invariant attributes. METHODS: We used panel data from two to four waves of a Japanese occupational cohort survey, focusing on 30,206 observations of 10,106 individuals (7,669 men and 2,437 women) aged 18-76 years. We estimated first-difference and mean-centered fixed effects models to examine how changes in 10 health checkup items were associated with changes in LTPA intensity. We considered four LTPA intensity levels (none, low, moderate, and vigorous), based on self-reported assessments. RESULTS: For men, low-density lipoprotein cholesterol levels, glycated hemoglobin levels, body mass index, and waist circumference improved when LTPA intensity was increased even at a low level, whereas triglyceride, high density lipoprotein cholesterol, and fasting blood glucose levels improved when LTPA intensity was increased to moderate or vigorous levels. Blood pressure (both systolic and diastolic) and total cholesterol levels were only modestly responsive to changes in LTPA intensity. For women, blood pressure (both systolic and diastolic) and waist circumference were negatively associated with LTPA intensity, whereas the other variables showed more modest effects. CONCLUSIONS: The results suggest that even low- to moderate-intensity LTPA can improve health checkup results; however, the lowest LTPA intensity associated with improvement in health depends on health-risk factors as well as gender. PMID- 27265534 TI - Differential gene expression associated with inflammation in peripheral blood cells of patients with pneumoconiosis. AB - OBJECTIVES: To study expression changes in inflammation-related genes in peripheral blood of patients with pneumoconiosis and to explore the possibility of these genes as pneumoconiosis biomarkers. METHODS: Peripheral blood samples of patients with pneumoconiosis patients and controls were collected, and total RNA of the blood cells were extracted and reverse transcribed to cDNA. Screenings of deferentially expressed genes associated with inflammation between patients with pneumoconiosis and controls were performed using real-time quantitative PCR array and the expressions of the three most upregulated genes were confirmed by real time PCR. RESULTS: The expression of 11 genes was significantly altered in patients with pneumoconiosis compared with those of the control. Among these 11 genes, 8 genes were upregulated and 3 were downregulated. Preliminary results indicated that interleukin 6 (IL-6) mRNA expression in patients with pneumoconiosis was higher than that in controls (P=0.019). The level of IL6 mRNA expression in the patients was higher than that in non-smoking controls, but it was neither affected by type and stage of pneumoconiosis nor by time of contact with dust. CONCLUSIONS: IL6 was possibly involved in the development of pneumoconiosis. PMID- 27265535 TI - Anaphylaxis in laboratory workers because of rodent handling: two case reports. AB - INTRODUCTION: Occupational allergy to rodents among laboratory animal workers is common. Most patients generally experience allergic symptoms after the first few years of work. Associated symptoms are usually mild, such as rhinoconjunctivits, urticaria, and asthma. Anaphylaxis, although rare, could be severe and life threatening. METHODS: We have described in this study two cases of laboratory workers that developed skin and respiratory reactions following laboratory rat and mouse bites, consistent with anaphylaxis. RESULTS: Skin testing was found positive for rat epithelium in the patient with anaphylaxis due to rat bite. Elevated levels of specific IgE antibodies against rat and mouse epitheliums were also detected in both the patients. CONCLUSION: These cases illustrate a severe hypersensitivity reaction that could potentially occur in occupational workers that are in close contact with rodents. Reduction of allergen exposure, regular screening, and job modification could be beneficial for affected individuals. Health care workers should be made aware that anaphylaxis could be a serious consequence of laboratory animal bites, particularly in those already sensitized. PMID- 27265536 TI - Interaction of engineered nanomaterials with hydrophobic organic pollutants. AB - As nanomaterials become an increasing part of everyday consumer products, it is imperative to monitor their potential release during production, use and disposal, and to assess their impact on the health of humans and the ecosystem. This necessitates research to better understand how the properties of engineered nanomaterials (ENMs) lead to their accumulation and redistribution in the environment, and to assess whether they could become novel pollutants or if they can affect the mobility and bioavailability of other toxins. This study focuses on understanding the influence of nanostructured-TiO2 and the interaction of multi-walled carbon nanotubes with organic pollutants in water. We studied the adsorption and water phase dispersion of model pollutants with relatively small water solubility (i.e., two- and three-ring polyaromatic hydrocarbons and insecticides) with respect to ENMs. The sorption of pollutants was measured based on water phase analysis, and by separating suspended particles from the water phase and analyzing dried samples using integrated thermal-chromatographic-mass spectroscopic (TGA/GC/MS) techniques. Solid phase analysis using a combination of TGA/GC/MS is a novel technique that can provide real-time quantitative analysis and which helps to understand the interaction of hydrophobic organic pollutants and ENMs. The adsorption of these contaminants to nanomaterials increased the concentration of the contaminants in the aqueous phase as compared to the 'real' partitioning due to the octanol-water partitioning. The study showed that ENMs can significantly influence the adsorption and dispersion of hydrophobic/low water soluble contaminants. The type of ENM, the exposure to light, and the water pH have a significant influence on the partitioning of pollutants. PMID- 27265537 TI - Chemerin and interleukin-6 levels in obese individuals following periodontal treatment. AB - OBJECTIVE: To investigate changes in the levels of gingival crevicular fluid (GCF) chemerin and interleukin-6 (IL-6) in both obese/non-obese individuals with periodontitis following non-surgical periodontal therapy. METHODS: Individuals (n = 80) were split into four groupings according to periodontal/anthropometric parameters: (i) periodontal healthy without obesity; (ii) chronic periodontitis (CP) without obesity; (iii) periodontal healthy with obesity; and (iv) CP with obesity. Individuals with periodontitis were treated with non-surgical periodontal therapy. Both GCF sampling procedures and clinical periodontal measures were performed prior to treatment and 6 weeks thereafter. Enzyme-linked immunosorbent assay was utilized to measure both chemerin and IL-6 levels. RESULTS: Greater values for chemerin and IL-6 were observed in obese individuals compared to their non-obese controls and in individuals with CP compared to their periodontal healthy controls (P < 0.008), which decreased following therapy (P < 0.05). A positive correlation was found between chemerin and IL-6 in obese groups (P < 0.05). A comprehensive overview of all groups showed a statistically significant positive correlation among chemerin, along with IL-6, waist-to-hip ratio, body mass index, and clinical attachment levels (P < 0.05). CONCLUSION: It could be concluded that chemerin levels may act as both diagnostic and prognostic indicators. Chemerin may also play an integral part in the pathologic mechanisms that relate adipokines to both periodontal disease and obesity. PMID- 27265538 TI - Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications. AB - Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. PMID- 27265549 TI - Second-generation antipsychotics and quality of life in schizophrenia. PMID- 27265548 TI - Effects of first-generation antipsychotics versus second-generation antipsychotics on quality of life in schizophrenia: a double-blind, randomised study. AB - BACKGROUND: Whether or not second-generation antipsychotics (SGAs) represent an advantage over first-generation antipsychotics (FGAs) in the treatment of schizophrenia is not certain. Effectiveness studies published in the past 10 years have not unequivocally confirmed the superiority of SGAs over FGAs. We aimed to compare quality of life in patients with schizophrenia on an FGA strategy with those on an SGA strategy. METHODS: In the multicentre, randomised, double-blind Neuroleptic Strategy Study (NeSSy), we recruited participants (aged 18-65 years) with schizophrenia (ICD-10: F20.X) who required treatment initiation or a change in treatment, from 14 psychiatric university hospitals and state hospitals in Germany. Double randomisation allowed for restricted selection of a treatment within each antipsychotic drug group (FGA or SGA) for an individual patient: first, patients were assigned with a random number table to two of six possible drug pairs, each pair consisting of an FGA (haloperidol [3-6 mg] or flupentixol [6-12 mg]) given orally and an SGA (aripiprazole [10-20 mg], olanzapine [10-20 mg], or quetiapine [400-800 mg]) given orally, and the investigator then selected which pair was best suited to the patient; a second, double-blind random assignment allocated either the FGA or the SGA from the investigator-chosen pair to the patient. Treatment duration was 24 weeks. Primary outcomes were change from baseline to week 24 in quality of life (SF-36) and clinical global impression (CGI-I), analysed in all randomly assigned patients who received at least one dose of the study drug. Safety was assessed in a safety set, consisting of all randomly assigned patients who received at least one dose of the study drug, coinciding with the set of the efficacy analyses. The study is registered with ClinicalTrials.gov, number NCT01164059; German Clinical Trials Register, number DRKS00000304; WHO ICTRP, number U1111-1112-9727; and EudraCT, number 2009-010966-47. FINDINGS: Between April 1, 2010, and May 31, 2013, 149 patients were randomly assigned, 69 to FGA treatment and 80 to SGA treatment. 136 patients received at least one dose of study drug (63 in the FGA group, 73 in the SGA group). Mean area under the curve (AUC) values of SF-36 were significantly higher in the SGA group than in the FGA group (85.1 [SD 14.7] vs 79.7 [17.3], p=0.0112). Mean AUC values for CGI-I scores decreased in both groups, but were not significantly different between the two groups (3.39 [SD 0.89] in the FGA group vs 3.26 [0.92] in the SGA group, p=0.3423). 30 (48%) of 63 patients given FGAs had at least one adverse event compared with 42 (57%) of 73 patients given an SGA (p=0.3019); the most common were nervous system disorders (18 [60%] of 30 in the FGA group vs 19 [45%] of 42 in the SGA group) and psychiatric disorders (ten [33%] vs 16 [38%]). One patient died after cessation of study drug (olanzapine), most likely as a result of an illicit drug overdose. The increase in body-mass index (BMI) was significantly higher in the SGA group than in the FGA group (p=0.0021 at week 6 and p=0.0041 at week 24). INTERPRETATION: Improvement of patient-reported quality of life was significantly higher in patients with schizophrenia given SGAs than in those given FGAs, when treatment selection was individualised. This advantage, however, has to be weighed against the potential metabolic adverse effects of some SGAs. FUNDING: German Federal Ministry of Education and Research. PMID- 27265550 TI - An analysis of nursing students' decision-making in teams during simulations of acute patient deterioration. AB - AIM: The aim of this study was to examine the decision-making of nursing students during team based simulations on patient deterioration to determine the sources of information, the types of decisions made and the influences underpinning their decisions. BACKGROUND: Missed, misinterpreted or mismanaged physiological signs of deterioration in hospitalized patients lead to costly serious adverse events. Not surprisingly, an increased focus on clinical education and graduate nurse work readiness has resulted. DESIGN: A descriptive exploratory design. METHODS: Clinical simulation laboratories in three Australian universities were used to run team based simulations with a patient actor. A convenience sample of 97 final year nursing students completed simulations, with three students forming a team. Four teams from each university were randomly selected for detailed analysis. Cued recall during video review of team based simulation exercises to elicit descriptions of individual and team based decision-making and reflections on performance were audio-recorded post simulation (2012) and transcribed. RESULTS: Students recalled 11 types of decisions, including: information seeking; patient assessment; diagnostic; intervention/treatment; evaluation; escalation; prediction; planning; collaboration; communication and reflective. Patient distress, uncertainty and a lack of knowledge were frequently recalled influences on decisions. CONCLUSIONS: Incomplete information, premature diagnosis and a failure to consider alternatives when caring for patients is likely to lead to poor quality decisions. All health professionals have a responsibility in recognizing and responding to clinical deterioration within their scope of practice. A typology of nursing students' decision-making in teams, in this context, highlights the importance of individual knowledge, leadership and communication. PMID- 27265551 TI - Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent. AB - Flavonoid compounds are strong antioxidant and antifungal agents but their applications are limited due to their poor dissolution and bioavailability. The use of nanotechnology in agriculture has received increasing attention, with the development of new formulations containing active compounds. In this study, kaempferol (KAE) was loaded into lecithin/chitosan nanoparticles (LC NPs) to determine antifungal activity compared to pure KAE against the phytopathogenic fungus Fusarium oxysporium to resolve the bioavailability problem. The influence of formulation parameters on the physicochemical properties of KAE loaded lecithin chitosan nanoparticles (KAE-LC NPs) were studied by using the electrostatic self-assembly technique. KAE-LC NPs were characterized in terms of physicochemical properties. KAE has been successfully encapsulated in LC NPs with an efficiency of 93.8 +/- 4.28% and KAE-LC NPs showed good physicochemical stability. Moreover, in vitro evaluation of the KAE-LC NP system was made by the release kinetics, antioxidant and antifungal activity in a time-dependent manner against free KAE. Encapsulated KAE exhibited a significantly inhibition efficacy (67%) against Fusarium oxysporium at the end of the 60 day storage period. The results indicated that KAE-LC NP formulation could solve the problems related to the solubility and loss of KAE during use and storage. The new nanoparticle system enables the use of smaller quantities of fungicide and therefore, offers a more environmentally friendly method of controlling fungal pathogens in agriculture. PMID- 27265552 TI - Trichinella britovi biomass in naturally infected pine martens (Martes martes) of Latvia. AB - Parasites of the genus Trichinella are cosmopolitan nematodes infecting primarily wild animals, which represent the main reservoirs of these zoonotic pathogens. To investigate the transmission patterns of Trichinella spp. from wild to domestic animals and to humans and for the risk assessment of these parasites in a geographical area, it is important to know the number of possible transmission events deriving from carcasses of infected hosts. For this purpose, the evaluation of the larval biomass in reservoir hosts is needed. No data is available on how to estimate the biomass of Trichinella spp. larvae in muscles of naturally infected animals. The aim of this study was to evaluate the larval biomass in naturally infected pine martens (Martes martes) of Latvia, in which the prevalence of Trichinella britovi infection was over 50%. Single muscles or group of muscles (abdomen, back, diaphragm, intercostal muscles, muscles from the head, left and right shoulders, lower and upper parts of the forelimbs and hind limbs, neck, rump with tail, and base and tip of the tongue) were collected from five skinned and eviscerated carcasses of T. britovi infected pine martens. Muscles were entirely removed from the bones and weighted. Each muscle or group of muscles was separately digested to detect the larvae per gram (LPG). Using linear regression, the larval burden in each muscle or group of muscles was evaluated to measure the possible prediction of the total animal larval burden (both as total number of larvae and as average LPG). All muscles were significantly predictive of the total burden with high "goodness of fit" (all adjusted R2>0.80; P<=0.01), and the left shoulder provided the highest adjusted R2 (0.999). Then, to estimate the Trichinella britovi biomass in the pine marten population of Latvia, recent literature data on prevalence (56.2%, 95% CI: 47.8 64.3) and geometric mean LPG (1.26, 95% CI: 0.89-1.79) in the limb muscles of a sample representative of the whole Latvian pine marten population, were used. Using the predictive estimated relationship between LPG in the limb and that in the entire animals and by the estimated animal population and their mean total muscle weight, the Trichinella britovi biomass in the pine marten population of Latvia was estimated to be of 6,647,092 (95% CI: 3,840,030-11,100,000) larvae. The assessment of the biomass in nature can help to understand the epidemiological pattern of these pathogens, to implement actions aimed at controlling the infection in target animal species, and to acquire basic information on the complex biology of this group of zoonotic nematodes. PMID- 27265553 TI - Remember Flint. PMID- 27265554 TI - "Evaluating the Quality of Medical Care": Donabedian's Classic Article 50 Years Later. PMID- 27265555 TI - Where Have All the Primary Care Doctors Gone? PMID- 27265556 TI - Hospital Community Benefit Spending: Leaning In on the Social Determinantsof Health. PMID- 27265557 TI - Global Budgets for Rural Hospitals. PMID- 27265558 TI - The Drug Price Controversy Nobody Notices. PMID- 27265559 TI - Using Publicly Available Data to Construct a Transparent Measure of Health Care Value: A Method and Initial Results. AB - POLICY POINTS: Using publicly available Hospital Compare and Medicare data, we found a substantial range of hospital-level performance on quality, expenditure, and value measures for 4 common reasons for admission. Hospitals' ability to consistently deliver high-quality, low-cost care varied across the different reasons for admission. With the exception of coronary artery bypass grafting, hospitals that provided the highest-value care had more beds and a larger average daily census than those providing the lowest-value care. Transparent data like those we present can empower patients to compare hospital performance, make better-informed treatment decisions, and decide where to obtain care for particular health care problems. CONTEXT: In the United States, the transition from volume to value dominates discussions of health care reform. While shared decision making might help patients determine whether to get care, transparency in procedure- and hospital-specific value measures would help them determine where to get care. METHODS: Using Hospital Compare and Medicare expenditure data, we constructed a hospital-level measure of value from a numerator composed of quality-of-care measures (satisfaction, use of timely and effective care, and avoidance of harms) and a denominator composed of risk-adjusted 30-day episode-of care expenditures for acute myocardial infarction (1,900 hospitals), coronary artery bypass grafting (884 hospitals), colectomy (1,252 hospitals), and hip replacement surgery (1,243 hospitals). FINDINGS: We found substantial variation in aggregate measures of quality, cost, and value at the hospital level. Value calculation provided additional richness when compared to assessment based on quality or cost alone: about 50% of hospitals in an extreme quality- (and about 65% more in an extreme cost-) quintile were in the same extreme value quintile. With the exception of coronary artery bypass grafting, higher-value hospitals were larger and had a higher average daily census than lower-value hospitals, but were no more likely to be accredited by the Joint Commission or to have a residency program accredited by the American Council of Graduate Medical Education. CONCLUSIONS: While future efforts to compose value measures will certainly be modified and expanded to examine other reasons for admission, the construct that we present could allow patients to transparently compare procedure and hospital-specific quality, spending, and value and empower them to decide where to obtain care. PMID- 27265560 TI - Getting It Right for Every Child: A National Policy Framework to Promote Children's Well-being in Scotland, United Kingdom. AB - POLICY POINTS: Getting It Right for Every Child (GIRFEC), a landmark policy framework for improving children's well-being in Scotland, United Kingdom, is a practice initiative signifying a distinct way of thinking, an agenda for change, and the future direction of child welfare policy. GIRFEC represents a unique case study of national transformative change within the contexts of children's well being and universal services and is of relevance to other jurisdictions. Implementation is under way, with an understanding of well-being and the requirement for information sharing enshrined in law. Yet there is scope for interpretation within the legislation and associated guidance. Inherent tensions around intrusion, data gathering, professional roles, and balancing well-being against child protection threaten the effectiveness of the policy if not resolved. CONTEXT: Despite persistent health inequalities and intergenerational deprivation, the Scottish government aspires for Scotland to be the best country for children to grow up in. Getting It Right for Every Child (GIRFEC) is a landmark children's policy framework to improve children's well-being via early intervention, universal service provision, and multiagency coordination across organizational boundaries. Placing the child and family "at the center," this approach marks a shift from welfare to well-being, yet there is still a general lack of consensus over how well-being is defined and measured. As an umbrella policy framework with broad reach, GIRFEC represents the current and future direction of children's/family policy in Scotland, yet large-scale practice change is required for successful implementation. METHODS: This article explores the origins and emergence of GIRFEC and presents a critical analysis of its incremental design, development, and implementation. FINDINGS: There is considerable scope for interpretation within the GIRFEC legislation and guidance, most notably around assessment of well-being and the role and remit of those charged with implementation. Tensions have arisen around issues such as professional roles; intrusion, data sharing, and confidentiality; and the balance between supporting well-being and protecting children. Despite the policy's intentions for integration, the service landscape for children and families still remains relatively fragmented. CONCLUSIONS: Although the policy has groundbreaking potential, inherent tensions must be resolved and the processes of change carefully managed in order for GIRFEC to be effective. It remains to be seen whether GIRFEC can fulfil the Scottish government's aspirations to reduce inequalities and improve lifelong outcomes for Scotland's children and young people. In terms of both a national children's well-being framework within a universal public service context and a distinct style of policymaking and implementation, the Scottish experience represents a unique case study of whole country, transformational change and is of relevance to other jurisdictions. PMID- 27265561 TI - The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience. AB - POLICY POINTS: Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families. Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late-diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis. Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence-based economic evaluations of disorders proposed for addition to the state-mandated newborn screening panel. CONTEXT: Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost-benefit models in Washington State as part of the rule-making process that resulted in the implementation of screening for medium-chain acyl CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. METHODS: We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer-reviewed literature. FINDINGS: The MCAD model projected a benefit-cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit cost ratio of 4.0-5.4 to 1 for a discount rate of 3%-4% and a plausible range of 1-2 percentage point reductions in deaths up to age 10 years. CONCLUSIONS: The Washington State cost-benefit models of newborn screening were broadly consistent with peer-reviewed literature, and their findings of net benefit appear to be robust to uncertainty in parameters. Public health newborn screening programs can develop their own capacity to project expected costs and benefits of expansion of newborn screening panels, although it would be most efficient if this capacity were shared among programs. PMID- 27265564 TI - Comparative ecotoxicology study of two neoteric solvents: Imidazolium ionic liquid vs. glycerol derivative. AB - In this study we have compared the acute ecotoxicity of two solvents, with very different structure and origin, but sharing many physical-chemical properties, so they can be used for similar purposes; a well-known ionic liquid 1-butyl-3 methylimidazolium hexafluorophosphate ([BMIM][PF6]) and a solvent partially derived from biomass, 3-bis(2,2,2-trifluoroethoxy)propan-2-ol (BTFIP). We have used three biomodels (Vibrio fischeri, Daphnia magna and Danio rerio) and performed the comparison applying the Environmental, Health and Safety (EHS) hazard assessment. According to the results, ecotoxicity of [BMIM][PF6] and BTFIP is quite similar in the simplest model Vibrio fischeri, while in Daphnia magna [BMIM][PF6] is clearly more toxic. However, in Danio rerio, toxicity of these chemicals is again quite similar and both can be classified as "nontoxic". The higher index value of [BMIM][PF6] in water mediate effect in the EHS assessment indicates that this ionic liquid is more dangerous than BTFIP, although accumulation and degradation properties have not been taken into account. Further studies will be necessary to ascertain these conclusions. PMID- 27265562 TI - Achieving Research Impact Through Co-creation in Community-Based Health Services: Literature Review and Case Study. AB - POLICY POINTS: Co-creation-collaborative knowledge generation by academics working alongside other stakeholders-is an increasingly popular approach to aligning research and service development. It has potential for "moving beyond the ivory towers" to deliver significant societal impact via dynamic, locally adaptive community-academic partnerships. Principles of successful co-creation include a systems perspective, a creative approach to research focused on improving human experience, and careful attention to governance and process. If these principles are not followed, co-creation efforts may fail. CONTEXT: Co creation-collaborative knowledge generation by academics working alongside other stakeholders-reflects a "Mode 2" relationship (knowledge production rather than knowledge translation) between universities and society. Co-creation is widely believed to increase research impact. METHODS: We undertook a narrative review of different models of co-creation relevant to community-based health services. We contrasted their diverse disciplinary roots and highlighted their common philosophical assumptions, principles of success, and explanations for failures. We applied these to an empirical case study of a community-based research-service partnership led by the Centre of Research Excellence in Quality and Safety in Integrated Primary-Secondary Care at the University of Queensland, Australia. FINDINGS: Co-creation emerged independently in several fields, including business studies ("value co-creation"), design science ("experience-based co-design"), computer science ("technology co-design"), and community development ("participatory research"). These diverse models share some common features, which were also evident in the case study. Key success principles included (1) a systems perspective (assuming emergence, local adaptation, and nonlinearity); (2) the framing of research as a creative enterprise with human experience at its core; and (3) an emphasis on process (the framing of the program, the nature of relationships, and governance and facilitation arrangements, especially the style of leadership and how conflict is managed). In both the literature review and the case study, co-creation "failures" could often be tracked back to abandoning (or never adopting) these principles. All co-creation models made strong claims for significant and sustainable societal impacts as a result of the adaptive and developmental research process; these were illustrated in the case study. CONCLUSIONS: Co-creation models have high potential for societal impact but depend critically on key success principles. To capture the nonlinear chains of causation in the co-creation pathway, impact metrics must reflect the dynamic nature and complex interdependencies of health research systems and address processes as well as outcomes. PMID- 27265566 TI - [Mood disorders and epilepsy surgery: A review]. AB - AIMS: Historically, there is a strong link between depression and epilepsy. Patients with epilepsy are four to five times more likely to develop a depressive syndrome. It seems that the link between epilepsy and depression is bidirectional. There is little data on mood disorders secondary to epilepsy surgery. The goal of epilepsy surgery is to reduce the number and frequency of attacks, which in turn would allow improvements in mood disorders and cognitive impairment. METHODS: A systematic search of the international literature was performed using the bibliographic search engines PubMed and Embase. The following MESH terms were used: epilepsy surgery AND (depression OR depressive disorder OR mood disorder). We also used the "related articles" of PubMed, bibliography surveys, conference abstracts and Google Scholar to identify additional relevant papers. RESULTS: Of the 130 studies found by the systematic search, 112 are excluded because they did not take into account the mood disorders secondary to epilepsy surgery. Fifteen studies are included in this review of the literature with a case study. Depression is the psychopathological condition that is the most frequently studied. According to several studies, the prevalence of depression is approximately 30% with nearly 70% of cases diagnosed during the first three months following epilepsy surgery. The majority of patients presented depressive symptoms during the first 3 to 12months after epilepsy surgery. In these studies, the risk of developing depression is correlated with the existence of previous depressive elements relative to the epilepsy surgery. A small number of studies reported cases of de novo depression. Studies have shown a correlation between very good to excellent control of epileptic seizures and a persistent improvement of mood disorders. It would seem that depressive symptoms post surgery are more common when the surgical intervention concerns the temporal lobe and in particular mesial resections. There are only very few cases of maniac episodes. Hamid et al. showed an increased risk of suicide waning after the epilepsy surgery over a period of 5years. CONCLUSION: Mood disorders are common psychiatric comorbidities in epilepsy surgery. The detection, prevention, and treatment of these symptoms in patients eligible for epilepsy surgery pose major challenges for psychiatrists and neurologists, requiring their close collaboration. PMID- 27265565 TI - Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment. AB - The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines' production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer. PMID- 27265567 TI - Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations. AB - Cyclooxygenase (COX; EC: 1.14.99.1), the key enzyme in prostaglandin production in the human body, is a major pharmacological target for developing anti inflammatory agents. Nonsteroidal anti-inflammatory drugs exhibit anti inflammatory and analgesic activities when inhibiting COX-2 but cause gastrointestinal toxicity and other side effects because of concurrent inhibition of COX-1. Thus, potent and safe inhibitors against COX-2 are urgently required. We constructed a novel docking-based pharmacophore model for screening selective COX-2 inhibitors and discovered compounds S1, S2, S3, and S4, which apparently inhibit COX-2. Particularly, S4 inhibits COX-2 in vitro and shows a potent anti inflammatory effect in vivo without cytotoxicity. Molecular docking analyses revealed that S4 interacted satisfactorily with the active site of COX-2 but not with that of COX-1. This reveals that S4 more specifically inhibits COX-2 and has potential for application in developing anti-inflammatory and anticancer agents. PMID- 27265568 TI - Tetrameric psuedo-peptide receptors with allosteric properties. AB - This paper reports the binding properties of tetrameric pseudo-peptide receptors for protonated cytidines. The receptors, which were isolated from a dynamic combinatorial chemistry (DCC) experiment, bind the analytes with affinities that depend on the presence or absence of excess acid, and with a stoichiometry that is both concentration and temperature dependent. PMID- 27265570 TI - Television Serials and Hematology. PMID- 27265571 TI - Graft-Versus-Host Disease (GVHD) An Evidence-Based Management Guidelines. PMID- 27265569 TI - Involvement of quinolinic acid in the neuropathogenesis of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease characterized by a progressive degeneration of central and peripheral motor neurons, leading to the atrophy of voluntary muscles. It has been previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in ALS. In particular, the neuroactive intermediate, quinolinic acid (QUIN) has been shown to accumulate with a concomitant decrease in other neuroprotective and immunomodulatory KP metabolites. Furthermore, multiple biochemical phenomena associated with QUIN cytotoxicity are present in ALS, suggesting that QUIN may play a substantial role in the pathogenesis of ALS. This review highlights the potential roles of QUIN in ALS, and explores KP modulation as a therapeutic candidate in ALS. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. PMID- 27265572 TI - Potential Involvement of Calcineurin in Regulating the State of Differentiation and Apoptosis of HL-60 Cells During Methylprednisolone-Treatment. AB - To evaluate the role of calcineurin (protein phosphatase type 2B, PP2B) in methylprednisolone-induced differentiation and apoptosis of leukaemic cells, we have investigated the induction of apoptosis, calcineurin specific protein phosphatase activity and expression of regulatory and catalytic subunits of calcineurin and calmodulin after induction of HL-60 leukaemic cells with methylprednisolone. The cells underwent differentiation and apoptosis within 72 hours time period after methylprednisolone added to cell culture media. Before apoptosis occurred, the specific calcineurin enzyme activity revealed gradual increase during the differentiation process. However, immunoblots of catalytic and regulatory subunits of calcineurin showed no amplification in the amount of these cellular signaling mediators during methylprednisolone-induced differentiation and apoptosis but calmodulin expression gradually increased during the process. Significant increase in the specific calcineurin enzyme activity during differentiation and apoptosis might be crucial to the posttranslational modifications of calcineurin during methylprednisolone-induced differentiation. PMID- 27265573 TI - Quantification of All-Trans-Retinoic Acid (ATRA) Dependent Expression of CXCR4 Gene in Acute Promyelocytic Leukaemia. AB - CXCR4 is the receptor of CXC chemokine SDF-1 and may play a role in the homing of hematopoietic stem cells. We have investigated the CXCR4 gene expression during ATRA treatment in acute promyelocytic leukaemia (APL) patients. APL is a characteristic disorder with a specific translocation between PML and RAR alpha genes on chromosome 15 and 17. ATRA-induced differentiation of APL cells is strictly dependent on the presence of PML-RAR alpha. In our study, five APL patiens were involved. Two samples from each patient were compared to each other: Primary diagnostic sample and a sample taken at remission. Quantitative real-time PCR (LightCycler) has been used for quantification, which is a recently developed method for rapid and sensitive detection of gene expression. CXCR4 gene ratios were found under-expressed in cases 1 and 6 with blast counts at diagnosis 18%, and 20% but only moderately under-expressed in cases two and four where the blast count was at diagnosis 50%, and 80%. It was over-expressed only in case three where the blast count was 95%. These findings indicate that ATRA treatment might be effective in CXCR4 gene expression related to amount of the blast population in APL. Further gene expression studies would be helpful to understand how ATRA works on CXCR4 related molecular pathways in APL pathogenesis. PMID- 27265574 TI - First Observation of Hemoglobin Pyrgos [beta83(EF7) Gly->Asp] in Turkish Population. AB - Hemoglobin Pyrgos [beta83 (EF7) Gly->Asp] is a rare hemoglobin variant. This report describes the first observation of this variant in an 18-year-old Turkish girl living in Isparta. PMID- 27265575 TI - Leiomyosarcoma of the Uterus Presenting with Thrombotic Thrombocytopenic Purpura. AB - Thrombotic thrombocytopenic purpura (TTP) typically presents with consumptive thrombocytopenia, non-immune intravascular hemolytic anemia, renal failure, various neurologic findings and fever. It is a clinical syndrome that can be associated with drugs such as ticlopidine, quinine, mitomycin C and cyclosporine, allogeneic stem cell transplantation, pregnancy, infections, autoimmune diseases and metastatic carcinoma. Here, we describe a 48-years- old women presented with full picture of TTP and diagnosed as leiomyosarcoma with further evaluation. She was successfully treated with multiple exchange transfusions and total excision of leiomyoma thereafter. As far as we know, this is the first case of leiomyosarcoma of the uterus presented with TTP. Therefore, the women with TTP, in whom no other cause can be found, should undergo a careful gynecological examination and pelvic ultrasonography should be performed. PMID- 27265576 TI - Hypercalcemia and Multiple Pathological Fractures in Chronic Lymphocytic Leukaemia: A Case Report. AB - Hypercalcemia is common in some lymphoproliferative disorders such as myeloma or T- cell leukaemialymphoma, but is rarely described in B-cell chronic lymphocytic leukaemia (CLL). A CLL patient who have been presented with multiple pathological fractures and widespread osteolytic lesions is reported. He was a 74 year old male with fractures of his bilateral humerus and radii and multiple osteolytic lesions of skull, fibula, femur and costals. On his admission to the hospital for the fractures he has been diagnosed as CLL. Hypercalcemia has also been documented. All the disorders that could be the reason of hypercalcemia have been ruled out. The open biopsy of bone marrow showed lymphocytic infiltration in which increased number of prolymphocytes are observed. Hypercalcemia arising in a patient with CLL may indicate a negative prognosis. PMID- 27265577 TI - The Outcome of Large B-Cell Lymphoma Evolving in a Hematopoietic Stem Cell Transplant Patient During Treatment of Chronic Graft-Versus-Host Disease. AB - Immunosuppression is a risk factor for the development of posttransplant lymphoproliferative disorder. This type of malignancy developed in an immunocompromised man. The patient presented with focal convulsion starting from right face and right arm followed by two generalized convulsions with one minute interval. Diagnosis was made by computed tomographic (CT) scan of the cranium following oral and intravenous administration of contrast dyes which revealedmass leisons in the frontotemporal lobe and by stereotaxic biopsy. Tissue sections showed a malignant tumor cell infiltration with large areas of necrosis and many mitoses. Many tumor cells were positive for CD 20 and CD 10. These findings were consistent with large B-cell lymphoma. Central nervous system radiation with a dose of 56 Gy was given with clinical and radiological improvement. The patient died due to multiorgan failure. Finally, the immunocompromised patients should be closely followed for the development of lymphoproliferative disorder. PMID- 27265578 TI - Images in Hematology. PMID- 27265579 TI - Aspirin Responsive Thrombotic Complications in Thrombocythemia Vera. A Novel Platelet-Mediated Arterial Thrombophilia. PMID- 27265580 TI - [Cardiomyopathy induced by frequent premature ventricular contractions]. AB - We report on the rare case of 7-year-old child presenting with frequent and apparently benign premature ventricular complexes (VPC) and left ventricular dysfunction. No structural disease of the heart was seen at cardiological evaluation. Eighteen months after the introduction of an antiarrhythmic treatment with low-dose bisoprolol, Holter monitoring showed 70,000 VPC in 24h with left ventricular function remaining decreased. Six months after increasing the dose of bisoprolol, the VPC were less frequent and left ventricular function was completely normalized. This case was characteristic of a cardiomyopathy induced by frequent premature ventricular contractions. PMID- 27265581 TI - [Rectal prolapse revealing a tumor: The role of abdominal ultrasound]. AB - Rectal prolapse is rare in children and usually benign. However, there are various diseases that can be associated with it, such as cystic fibrosis or other causes of increased abdominal pressure. Here, we review the various underlying conditions that pediatricians or pediatric gastroenterologists should consider in the case of rectal prolapse. We report on three cases of children with a rectal prolapse and intra-abdominal tumors. Current recommendations and practice do not include a systematic check via abdominal imaging in cases of rectal prolapse. However, in some situations, imaging is indicated to detect a possible expansive process. Thus, in the presence of recurrent prolapse or of associated urinary or neurological signs, imaging is justified so as to allow for an early diagnosis and treatment of these neoplasms. Given its lack of radiation exposure and good sensitivity in children, ultrasound imaging is the first choice. PMID- 27265582 TI - [Severe gastric distension in an adolescent]. PMID- 27265583 TI - [Bacillus Calmette-Guerin osteomyelitis. A case report in a former preterm baby]. AB - Postvaccination osteo-articular mycobacterial infectious disease is a rare and potentially serious complication after Bacillus Calmette-Guerin (BCG) vaccine. We report on a case of a former preterm baby born at 30 weeks of gestation who was vaccinated with BCG Copenhagen strain at 2 months of age. He presented 6 months later with a painful limp, which was found to be a mono-articular osteitis of the right ankle. Histology of the biopsy showed signs of mycobacterial infection and molecular analysis confirmed a BCG infection. Blood tests did not reveal any immunodeficiency associated with the disease (IFN-gamma levels were normal). The course of the disease was favorable with 9 months of antibiotic therapy against mycobacteria. BCG complications should lead to screening for immunodeficiency. The prognosis of BCG osteitis is excellent if the disease is localized. No link between prematurity and BCG complications has been found to date. BCG vaccination of premature infant should be the same as for the general population. PMID- 27265584 TI - [Infant food diversification: Is the information available on the Internet valid?]. AB - INTRODUCTION: The Internet provides easy access to information on health, but the quality and validity of this information are variable. OBJECTIVES: To evaluate the quality of websites and the information provided on the timing and consequences of food diversification for infants. MATERIALS AND METHODS: We analyzed the websites addressing infant food diversification that appeared on the first two pages of the search engines Google, Yahoo, and Bing. The websites were selected from four different queries. We initially assessed (a) the structure of the websites with two instruments (the Criteria for Assessing the Quality of Health Information on the Internet (HITI) and NetScoring) and (b) the presence of certification (quality label Health on the Net [HON] Code). Secondly, we evaluated the content of the websites concerning the time of introducing five classes of foods (gluten, fat, allergenic foods, solid foods, and animal protein), the duration of breastfeeding, and four potential consequences of food diversification (allergy, nutritional, autoimmune, and cardiovascular). Our repository was based on the most recent recommendations of the French Society of Pediatrics published in 2008. RESULTS: In all, 19 websites were included. Six of 19 websites scored above average on the two instruments (average: 131.26/312 with NetScoring and 46.73/104 with HITI). No correlation was observed between the referencing of websites analyzed and the notes obtained with both instruments. A majority of the websites analyzed were consistent with the recommendation favoring breast milk (100%), the age of introducing meat proteins (74%), and the age of introducing gluten (63%). A majority of the websites disagreed on the age of introducing solid foods (16%). As four consequences, only the risk of allergy (63%) was cited by a majority of the sites. There was a small nonsignificant correlation between the results obtained for the website about introducing solid foods and the results obtained for the websites analyzed with the NetScoring and HITI instruments (Pearson coefficient 41%, p=0.07). CONCLUSION: The websites were in partial agreement with the French recommendations. To date, the pediatrician remains the main actor in guiding parents on food diversification. PMID- 27265585 TI - [BCGitis/BCGosis in children: Diagnosis, classification and exploration]. AB - The Bacille Calmette-Guerin (BCG) vaccine is used extensively worldwide, and more than 100 million children are vaccinated each year. This is a live vaccine that protects against severe tuberculosis in children. However, BCG complications, specific to the BCG vaccine, do occur, although the epidemiology differs from one country to another. Nevertheless, these complications are considered to be rare and range from benign local BCGitis to BCGosis, a potentially lethal disseminated disease. Etiologies of BCGitis/BCGosis can be related to the vaccine itself (technical errors, vaccinal strain) or to the patient. Indeed, it is well established that some immunodeficiencies, primary or acquired, can expose the patient to BCG disease. The diagnosis of a BCG disease lies on clinical examination and laboratory results. Recent advances in molecular biology help to distinguish BCG disease from other mycobacterial infections, especially from tuberculosis. When BCG complications have been confirmed, the underlying defect should be investigated, particularly if other features of immunodeficiency are reported, such as recurrent infection, failure to thrive, etc. Prognosis largely depends on the immune status, but also on the management of the BCG disease. Although the therapeutic protocols are still controversial, there are more and more publications on the diagnosis and management guidelines of the disease. PMID- 27265587 TI - Bone Marrow Transplantation in Thalassemia. PMID- 27265586 TI - Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: A nationwide cohort study. AB - Contemporary guidelines suggest anticoagulant treatment decisions in atrial fibrillation (AF) patients to be based on risk stratification for stroke. However, guidelines do not agree on the threshold for treatment initiation. We explored the variation in thromboembolic event rates in a non-anticoagulated AF population, according to different guideline threshold and methodological approaches. AF patients between 1998 and 2014 free from anticoagulant treatment were identified. Event rates for ischemic stroke and ischemic stroke/systemic embolism were explored. The overall ischemic stroke rate was 3.20 per 100 person years ('formal rate assessment'). For patients with a CHA2DS2-VASc score of 1 the ischemic stroke rate was 0.97 when using a 'formal rate assessment', 0.62 when using a 'conditioning on the future' approach, and 0.93 when using a 'censoring approach'. Rates for thromboembolism for the 'European treatment threshold' (CHA2DS2-VASc score of 1, males only) ranged 1.17 to 1.53. Rates for the 'U.S. treatment threshold' (CHA2DS2-VASc of 2) ranged from 1.95 to 2.33. Thromboembolic event rates differed markedly in non-anticoagulated AF patients according to the conflicting European and U.S. guideline treatment thresholds. Second, the choice of methodological approach has implications, thus we recommend using the censoring approach for event rate estimation among AF patients not on treatment. PMID- 27265588 TI - The Role of Interleukin-1 Inhibitors on Acute Myeloblastic Leukemia Blast Proliferation; Future Potential for Biotherapy. AB - The effect of interleukin-1 (IL-1) as an autocrine growth factor on the proliferation of the acute myeloblastic leukemia (AML) blasts was studied. Bone marrow specimens were obtained from nine patients with different subgroups of AML. IL-1 receptor antagonist (IL-1RA) and IL-1 beta neutralizing antibody (IL 1beta NA) alone or in combination were added to the culture mediums of the AML blast cultures for the detection of their inhibitory effect on AML blast cell proliferation and colony formation. Average colony numbers in the IL-RA, IL betaNA, and IL-IRA plus IL-IbetaNA included culture flasks, were 63.7 +/- 21.5 %, 69.5 +/- 19 %, 53.4 +/- 23.7 %, respectively, as compared to those of the control (p < 0.01). Inhibition of colony formation by IL-IRA plus IL-IbetaNA was more prominent than by IL-IbetaNA alone (p < 0.01). No correlation between the inhibition of AML blast colony ormation and FAB AML subgroups was seen. RESULT: Both IL-1RA or IL-IbetaNA or in combination induced varying degrees of inhibition on blast colony formation. IL-I inhibitory molecules could be considered as an alternative therapy for AML in patients whose blast cells are sensitive to IL-1 inhibition. PMID- 27265589 TI - Increased Serum Soluble CD23 and Soluble IL-2R Levels in Haematologic Malignancies. AB - Serum soluble CD23 (sCD23) and soluble IL-2 receptor (sIL-2R) levels increase not only in disorders with immune system activation, but also in hematological malignancies. They have been used as markers of disease progression and/or the response to therapy in lymphoproliferative disorders (LPD). In this study, we investigated the serum sCD23 and sIL-2R levels of 21 patients with different hematological malignancies [10 LPD, 6 multiple myeloma (MM), and 5 myelodysplastic syndrome (MDS)] before treatment, and compared them with 19 age- and sex- matched healthy subjects. Median sIL-2R levels were found to be significantly elevated in both the overall patient group and each of the subgroups. Median sCD23 levels were significantly higher in the overall patient group and in patients with LPD and MM. A positive correlation was found between sIL-2R and sCD23 levels in LPD. Our preliminary findings suggest that elevated serum levels of these soluble factors are not only markers of LPD but might be also used for other hematologic malignancies, except for MDS. Further studies should be designed to find out if it might be the result of an overactive immune system or not. PMID- 27265590 TI - Congenital Agranulocytosis (Kostmann's Syndrome) and G-CSF Therapy in an Infant. AB - Congenital agranulocytosis (Kostmann's Syndrome) is a rare autosomal recessive inherited disorder characterised by severe neutropenia, recurrent infections, and death in early life, with the bone marrow showing a maturation arrenst of myeloid cells at the myelocyte stage. The treatment of Kostmann's Syndrome with G-CSF results in rapid improvement. However, a few unexpected results with the use of G CSF, were reported. Here, we describe a 7-month-old female with Kostmann's Syndrome who had recurrent skin infections and a large pyogenic infection in the supravulvar region. The patient was treated with G-CSF successfully at low doses. The infectious process and the quality of lite of the patient improved. There was no adverse effect due to the dosage and the duration. Currently bone marrow transplantation is the best way to treat Kostmann's Syndrome. Nevertheless, our experience showed that G-CSF treatment in Kostmann's syndrome was highly effective and successfull on a short term basis. PMID- 27265591 TI - Massive Intraabdominal Relapse in a Patient with Acute Lymphocytic Leukemia. AB - Abdominal involvement in an isolated extramedullary relapse region in patients with acute lymphocytic leukemia (ALL) is a rare event, especially in patients in hematological remission. The literature related to this subject is very limited. In this study, a 23-year-old male patient, is presented who had been in remission for 4 years, was admitted because of an enlarged testis, and was found to have an abdominal bulky mass during physical examination. An early diagnosis of abdominal involvement is extremely important and must be kept in mind for ALL patients who are admitted for testicular relapse. PMID- 27265593 TI - p53 Gene Polymorphisms in the Turkish Population. AB - There different RFLP's on the p53 gene were studied in a healthy Turkish population. These RFLP's were located on the exon 4 (CD 47), exon 6 (CD 213) and intron 6 (A-G). CD 47 (C-T) was not present. CD 213 (G) occurred very rarely with a frequency of 0.0114. The frequency of the Int 6 A/G a alteration was found to be 0.70 for "G". The heterozygosity rate was 32.72%. PMID- 27265592 TI - Schistosoma mansoni Infection Following Allogeneic Bone Marrow Transplantation. AB - A case of Schistosoma mansoni infection in a 28 year old male after allogeneic bone marrow transplantation presenting with portal hypertension and gross hematuria is described. Schistosomiasis was confirmed by the discovery of parasites in the feces, together with the failure the patient to respond to multiple antimicrobial and antifungal treatment. After praziquantel administration, toxic or septic shock syndrome evolved and the patients died of acute renal failure on day 39 post-transplant. In this report, we would like to emphasize the importance of pre-transplant stool and urine cultures, and appropriate serologic tests in patients coming from endemic areas. Patients diagnosed with schistosomiasis must be treated at least 3 to 7 weeks before transplantation. PMID- 27265594 TI - Reoccurrence of retained placenta at a subsequent delivery: an observational study. AB - OBJECTIVE: To test the generalizability of previously reported increased risk of reoccurrence of retained placenta in yet another setting. METHODS: In this observational retrospective study we longitudinally followed women who had a vaginal delivery complicated by a partial or complete retained placenta at Edith Wolfson Medical Center between 1 January 2009 and 31 December 2012. The study group included parturient women who had a partial or complete retained placenta after a vaginal delivery (n = 90). The control group included parturient women who did not have a partial or complete retained placenta after a vaginal delivery from the same time period using the same inclusion criteria (n = 90). RESULTS: Retained partial or complete placenta at a previous delivery was found to be an independent risk factor for retained partial or complete placenta in a subsequent delivery (adjusted OR 9.8, 95%CI 1.2 to 80.6, p = 0.032) and for retained partial or complete placenta and/or postpartum hemorrhage in a subsequent delivery (adjusted OR 14.1, 95% CI 1.7 to 111.9, p = 0.012), after controlling for gestational age and induction of labor at previous delivery. CONCLUSION: Retained partial or complete placenta at an index delivery increases the risk of reoccurrence of retained partial or complete placenta in a subsequent delivery. PMID- 27265596 TI - Tumour immunology: A checkpoint for NK cells. PMID- 27265597 TI - The scaling of bite force and constriction pressure in kingsnakes (Lampropeltis getula): Proximate determinants and correlated performance. AB - Across the diversity of vertebrates, bite force has been studied and suggested to have important ecological and evolutionary consequences. However, there is a notable lineage of vertebrates that use this performance trait yet are missing from the bite-force literature: the snakes. Snakes often rely on biting during prey subjugation and handling. Many snakes bite and hold prey while a constriction coil is formed or while venom is being delivered, or both. Others use biting exclusively without employing any additional prey-handling behaviors. In addition to biting, constriction is an important predation mechanism. Here, I quantify bite force and constriction pressure in kingsnakes (Lampropeltis getula). Furthermore, I explore the proximate determinants of bite force as well as the relationship between biting and constriction performance. Bite force increased linearly with all head and body measures. Of these, head height was the best predictor of bite force. Bite force in kingsnakes was within the range of values reported for lizards, but their relative performance was lower for their head size compared to lizards. Peak constriction pressure also increased with all body measures. Biting and constricting use 2 different parts of the musculoskeletal system and are positively and significantly correlated with one another. Future work targeting a greater diversity of snakes that rely more heavily on biting may reveal a greater range of bite performance in this diverse and successful vertebrate group. PMID- 27265598 TI - Insights on the (Auto)Photocatalysis of Ferritin. AB - Traditionally, ferritin has been considered a photocatalyst capable of photo oxidizing organic molecules and transferring electrons to external electron acceptors when irradiated by UV-visible light. We have designed new approaches to resolve the uncertainties regarding its photocatalytical mechanism. Experiments with an Fe(II) chelator, an electrochromic indicator, and recombinant ferritin proteins indicate that the excited electrons at the conduction band of the ferritin core do not cross the protein shell. Instead, irradiation causes the electrons to reduce the ferrihydrite core to produce Fe(II) ions. These Fe(II) ions exit the protein shell to reduce electron acceptors. In the absence of electron acceptors or chelators, Fe(II) re-enters ferritin. PMID- 27265595 TI - Origins of the cytolytic synapse. AB - Cytotoxic T lymphocytes (CTLs) kill virus-infected and tumour cells with remarkable specificity. Upon recognition, CTLs form a cytolytic immune synapse with their target cell, and marked reorganization of both the actin and the microtubule cytoskeletons brings the centrosome up to the plasma membrane to the point of T cell receptor signalling. Secretory granules move towards the centrosome and are delivered to this focal point of secretion. Such centrosomal docking at the plasma membrane also occurs during ciliogenesis; indeed, striking similarities exist between the cytolytic synapse and the primary cilium that throw light on the possible origins of immune synapses. PMID- 27265599 TI - Purulent pericarditis with left ventricular pseudo-aneurysm. PMID- 27265601 TI - Extranodal Lymphoma of the Central Nervous System and Spine. AB - With a strong predilection for immunocompromised groups and a poorly explained increase in prevalence among those with normal immune status, lymphoma now accounts for approximately 6% of all primary brain tumors. Recent advances in multiagent chemotherapy and monoclonal antibody therapy have promoted longer-term survival, although a definitive cure remains elusive. Extranodal lymphoma of the spine is more often caused by secondary dissemination from systemic disease and less often the primary site of origin. This article reviews a broad spectrum of clinical, etiologic, and pathologic features that frequently intersect with common radiologic findings of this disease. PMID- 27265600 TI - Pathology of Extranodal Lymphoma. AB - An overview of the pathology of extranodal lymphoma is presented. The emphasis of this presentation is on the classification system of extranodal lymphomas, including both B-cell and T-cell lymphomas, based on their morphology, phenotype, and molecular alterations. PMID- 27265602 TI - Primary Extranodal Lymphoma of the Thorax. AB - Primary pulmonary lymphomas represent a pathologically heterogeneous group of disorders that often share imaging features, which include peribronchovascular nodules and masses or areas of nonresolving consolidation. Primary mediastinal B cell lymphoma is an extranodal non-Hodgkin lymphoma seen in younger patients that has imaging and pathologic features that demonstrate some degree of overlap with Hodgkin lymphoma. Primary lymphomas of the pleural space are rare and associated with concomitant viral infections. PMID- 27265603 TI - Cardiac Lymphoma. AB - Lymphoma of the heart and pericardium may develop in up to 25% of patients with disseminated nodal disease, but primary cardiac lymphoma is rare. The majority are diffuse large B-cell lymphomas, which arise in immunocompetent older individuals, men twice as often as women. Subsets are found in immunocompromised patients, including those with HIV-AIDS or allograft recipients. Cardiac lymphomas tend to arise in the wall of the right heart, especially right atrium, with contiguous infiltration of epicardium and pericardium. Pericardial implants and effusions are common. The disease is often multifocal in the heart, but cardiac valves are usually spared. PMID- 27265604 TI - Extranodal Lymphoma of the Breast. AB - Extranodal lymphoma represents fewer than 0.5% of all breast malignancies. Secondary involvement of the breast with lymphoma is more common than primary breast lymphoma. The most common primary breast lymphoma is B-cell lymphoma. The initial imaging study of choice for a woman with a new breast mass is a diagnostic mammogram. In younger women ultrasound is more commonly the first imaging modality performed. Diagnosis is made from image-guided or physical examination-directed needle biopsy. Treatment is different from that for breast cancer, in that surgery is not the mainstay. Patients with breast lymphoma are treated primarily with chemotherapy and radiation. PMID- 27265605 TI - Pediatric Extranodal Lymphoma. AB - Lymphoma is the third most common pediatric neoplasm. Non-Hodgkin lymphoma (NHL) accounts for nearly half of cases and commonly involves extranodal sites. Compared with adults, this histologic spectrum of pediatric NHL is very narrow and consists of aggressive tumors. Patients typically present with widespread disease. Generally, NHL occurring in children includes Burkitt lymphoma, lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large cell lymphoma. Staging and assessment of therapeutic response are usually based on FDG PET/CT. Due to the increased susceptibility of young patients to the effects of ionizing radiation, alternative methods of imaging are being explored. PMID- 27265606 TI - Imaging of Extranodal Genitourinary Lymphoma. AB - The genitourinary (GU) system is commonly affected by disseminated lymphoma. Rarely, lymphoma can originate from and remain localized to one of the GU organs and thus presents as primary extranodal disease. Up to 40% of lymphomas present as extranodal disease, with only 3% having the GU system as the primary site of involvement. This article describes and correlates the radiologic and pathologic features of extranodal lymphomatous disease affecting the GU system with specific focus on the kidneys, adrenal glands, testicles, and ovaries. Lymphoma of the uterine body and cervix, external female genitalia, urinary bladder, and prostate gland is briefly discussed. PMID- 27265607 TI - Gastrointestinal Lymphoma: Radiologic-Pathologic Correlation. AB - Extranodal lymphoma is a heterogeneous group of hematologic neoplasms that can affect every abdominal organ, with distinctive pathologic, radiologic, and clinical features. The radiologic findings are closely related to the underlying pathophysiology, and an understanding of these characteristic features should facilitate recognition of extranodal lymphoma and its various subtypes. Within the abdomen, lymphoma is found most commonly in the gastrointestinal tract, especially the stomach. This article presents the findings in gastrointestinal tract lymphoma. PMID- 27265608 TI - Primary Musculoskeletal Lymphoma. AB - Primary lymphoma of bone and soft tissue is rare and almost invariably of B-cell origin. Osseous lymphoma usually reveals aggressive bone destruction and associated soft tissue extension. Soft tissue involvement is optimally depicted by MR imaging. Cortical destruction allowing communication between the intraosseous and soft tissue components may be subtle with small striations of extension. Lymphoma of the deep soft tissues usually reveals long cones of intramuscular or intermuscular tumor again best depicted by MR imaging. Cutaneous or subcutaneous lymphoma demonstrates multiple nodules and plaquelike thickening. PMID- 27265609 TI - Imaging of Extranodal Lymphoma. PMID- 27265610 TI - Musculoskeletal and central pain at 1 year post-stroke: associated factors and impact on quality of life. AB - BACKGROUND AND PURPOSE: Pain is common in post-stroke patients and has been shown to be associated with depression, fatigue, and decreased quality of life (QOL). However, studies examining different types of post-stroke pain are scarce. We investigated differences in the related factors and their QOL impacts between musculoskeletal pain (MSP) and central post-stroke pain (CPSP). METHODS: We assessed 364 consecutive stroke patients who were admitted to Asan Medical Center and contacted 12 months after stroke onset. We categorized pain and paresthesia as MSP, CPSP, combined pain, or other pain. Post-stroke depression (Beck Depression Inventory), fatigue (Fatigue Severity Scale), sleep disturbance (Verran Snyder-Halpern scale), social support (ENRICHED Social Support Instrument), and QOL (Medical Outcome Study 36-Item Short Form) were assessed. RESULTS: Of the 364 patients analyzed, 135 (37.1%) had pain, 78 (21.4%) had MSP, 22 (6.0%) had CPSP, 16 (4.4%) had combined pain, and 19 (5.2%) had other pain. In multivariate analyses, CPSP was related to modified Rankin scale (P=.004), sensory dysfunction (P<.001), thalamus lesion (P=.001), medulla lesion (P=.007), and fatigue (P=.026). MSP was related to motor dysfunction (P<.001) and fatigue (P=.003). QOL varied among groups with different types of pain (P<.001) and was the poorest in patients with combined pain. CONCLUSIONS: Pain is common 12 months post-stroke. The factors associated with CPSP and MSP differ, but are both closely associated with fatigue rather than depression. QOL is the poorest in patients with combined pain. Management of pain and fatigue may be important for improving the QOL in stroke patients. PMID- 27265611 TI - An Automated High-throughput Array Microscope for Cancer Cell Mechanics. AB - Changes in cellular mechanical properties correlate with the progression of metastatic cancer along the epithelial-to-mesenchymal transition (EMT). Few high throughput methodologies exist that measure cell compliance, which can be used to understand the impact of genetic alterations or to screen the efficacy of chemotherapeutic agents. We have developed a novel array high-throughput microscope (AHTM) system that combines the convenience of the standard 96-well plate with the ability to image cultured cells and membrane-bound microbeads in twelve independently-focusing channels simultaneously, visiting all wells in eight steps. We use the AHTM and passive bead rheology techniques to determine the relative compliance of human pancreatic ductal epithelial (HPDE) cells, h TERT transformed HPDE cells (HPNE), and four gain-of-function constructs related to EMT. The AHTM found HPNE, H-ras, Myr-AKT, and Bcl2 transfected cells more compliant relative to controls, consistent with parallel tests using atomic force microscopy and invasion assays, proving the AHTM capable of screening for changes in mechanical phenotype. PMID- 27265612 TI - Hepatitis E seroprevalence and related risk factors among seafood processing workers: a cross-sectional survey in Shandong Province, China. AB - OBJECTIVE: This study aimed to assess the seroprevalence of hepatitis E virus (HEV) infection and the potential risk factors for acquiring HEV infection in the seafood processing factories in Yantai City of Shandong Province, China. METHODS: A cross-sectional study was conducted in five randomly selected seafood processing factories in Yantai City. Subjects were 15-66 years of age and were raw seafood processing workers, semi-finished products processing workers, and administrative staff, etc. Each participant completed a structured questionnaire and agreed to blood drawing. Anti-HEV IgG antibody was detected in the blood samples by ELISA method. RESULTS: A total of 1028 of 1044 eligible workers were tested for HEV IgG antibody (response rate 98.5%). The prevalence of HEV IgG seropositivity was found to be 22.20%. Occupation was significantly associated with anti-HEV IgG antibody seropositivity (p<0.05). Subjects who had direct contact with raw seafood had a higher anti-HEV IgG antibody prevalence (32.54%) than the semi-finished products processing workers (24.74%) and less exposed group (11.85%). HEV seroprevalence in the workers showed an increasing trend with the increase in working years, and this phenomenon was most obvious in raw seafood processing workers. CONCLUSIONS: There is a higher risk of HEV infection in those who have direct contact with raw seafood. This study will help identify the risk factors for HEV infection and provide guidance on controlling HEV infection in the seafood processing occupations. PMID- 27265613 TI - Oil-Soluble Polymer Brush Grafted Nanoparticles as Effective Lubricant Additives for Friction and Wear Reduction. AB - The development of high performance lubricants has been driven by increasingly growing industrial demands and environmental concerns. Herein, we demonstrate oil soluble polymer brush-grafted inorganic nanoparticles (hairy NPs) as highly effective lubricant additives for friction and wear reduction. A series of oil miscible poly(lauryl methacrylate) brush-grafted silica and titania NPs were synthesized by surface-initiated atom transfer radical polymerization. These hairy NPs showed exceptional stability in poly(alphaolefin) (PAO) base oil; no change in transparency was observed after being kept at -20, 22, and 100 degrees C for >=55 days. High-contact stress ball-on-flat reciprocating sliding tribological tests at 100 degrees C showed that addition of 1 wt % of hairy NPs into PAO led to significant reductions in coefficient of friction (up to ~40 %) and wear volume (up to ~90 %). The excellent lubricating properties of hairy NPs were further elucidated by the characterization of the tribofilm formed on the flat. These hairy NPs represent a new type of lubricating oil additives with high efficiency in friction and wear reduction. PMID- 27265619 TI - The role of enamel thickness and refractive index on human tooth colour. AB - OBJECTIVES: To investigate the role of enamel thickness and refractive index (n) on tooth colour. METHODS: The colour and enamel thickness of fifteen extracted human central incisors were determined according to CIELab colour scale using spectrophotometer (Crystaleye) and swept-source optical coherence tomography (SS OCT), respectively. Subsequently, labial enamel was trimmed by approximately 100MUm, and the colour and remaining enamel thickness were investigated again. This cycle was repeated until dentin appeared. Enamel blocks were prepared from the same teeth and their n were obtained using SS-OCT. Multiple regression analysis was performed to reveal any effects of enamel thickness and n on colour difference (DeltaE00) and differences in colour parameters with CIELCh and CIELab colour scales. RESULTS: Multiple regression analysis revealed that enamel thickness (p=0.02) and n of enamel (p<0.001) were statistically significant predictors of DeltaE00 after complete enamel trimming. The n was also a significant predictor of DeltaH' (p=0.01). Enamel thickness and n were not statistically significant predictors of DeltaL', DeltaC', Deltaa* and Deltab*. CONCLUSIONS: Enamel affected tooth colour, in which n was a statistically significant predictor for tooth colour change. CLINICAL SIGNIFICANCE: Understanding the role of enamel in tooth colour could contribute to development of aesthetic restorative materials that mimic the colour of natural tooth with minimal reduction of the existing enamel. PMID- 27265620 TI - Single-Dose Basiliximab Induction in Low-Risk Renal Transplant Recipients. AB - OBJECTIVES: To compare the efficacy of a single dose of basiliximab with two doses in preventing acute rejection in selected low-risk renal transplant recipients. METHODS: This observational study of 760 kidney transplant recipients considered to be at low immunologic risk (peak panel reactive antibody less than 10%) compared patient and graft outcomes following a single-dose versus a two dose regimen of basiliximab. MAIN RESULTS: No differences were found in patient survival (92% vs 92%, p=0.6), graft survival (86% vs 83%, p=0.2), acute rejection (cellular [4% vs 7%, p=0.2], antibody-mediated rejection [19% vs 19%, p=0.9]), or opportunistic infections (34% vs 30%, p=0.3) between the single versus two-dose regimens, respectively. In multivariate analyses, the number of doses of basiliximab was not associated with acute rejection or patient/graft survival despite adjustment with Cox regression and propensity scores. However, delayed graft function (DGF), donor age older than 65 years, and human leukocyte antigen mismatch of 3 or higher were associated with acute rejection (hazard ratio [HR] 2.64, 1.91, and 1.57, respectively, p<=0.04), and DGF and diabetes were associated with death/graft loss (HR 2.56 and 1.63, respectively, p<=0.009). PRINCIPAL CONCLUSIONS: A single dose of basiliximab is safe and effective for induction in low-risk kidney transplant recipients. PMID- 27265614 TI - Membrane remodelling in bacteria. AB - In bacteria the ability to remodel membrane underpins basic cell processes such as growth, and more sophisticated adaptations like inter-cell crosstalk, organelle specialisation, and pathogenesis. Here, selected examples of membrane remodelling in bacteria are presented and the diverse mechanisms for inducing membrane fission, fusion, and curvature discussed. Compared to eukaryotes, relatively few curvature-inducing proteins have been characterised so far. Whilst it is likely that many such proteins remain to be discovered, it also reflects the importance of alternative membrane remodelling strategies in bacteria where passive mechanisms for generating curvature are utilised. PMID- 27265621 TI - Selective deletion of Smad4 in postnatal germ cells does not affect spermatogenesis or fertility in mice. AB - SMAD4 is the central component of canonical signaling in the transforming growth factor beta (TGFbeta) superfamily. Loss of Smad4 in Sertoli cells affects the expansion of the fetal testis cords, whereas selective deletion of Smad4 in Leydig cells alone does not appreciably alter fetal or adult testis development. Loss of Smad4 in Sertoli and Leydig cells, on the other hand, leads to testicular dysgenesis, and tumor formation in mice. Within the murine testes, Smad4 is also expressed in germ cells of the seminiferous tubules. We therefore, crossed Ngn3 Cre or Stra8-Cre transgenic mice with Smad4-flox mice to generate conditional knockout animals in which Smad4 was specifically deleted in postnatal germ cells to further uncover cell type-specific requirement of Smad4. Unexpectedly, these germ-cell-knockout mice were fertile and did not exhibit any detectable abnormalities in spermatogenesis, indicating that Smad4 is not required for the production of sperm; instead, these data indicate a cell type-specific requirement of Smad4 primarily during testis development. Mol. Reprod. Dev. 83: 615-623, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27265622 TI - Canine echinococcosis: the predominance of immature eggs in adult tapeworms of Echinococcus granulosus in stray dogs from Tunisia. AB - Canine echinococcosis is caused by the adult tapeworm of Echinococcus granulosus. As intermediate hosts, humans and livestock become infected following ingestion of eggs that are passed in the faeces of dogs. Mature eggs develop into hydatid cysts in different organs, leading to hydatid disease, which is a serious public health problem. In the present study, we investigated the proportion of mature eggs of E. granulosus in 140 dogs from three regions of Tunisia. The results showed the predominance of immature E. granulosus eggs in infected dogs and the occurrence of a small proportion of oncospheres. The ability of immature eggs to infect humans and livestock is discussed. PMID- 27265623 TI - Global update on the susceptibility of human influenza viruses to neuraminidase inhibitors, 2014-2015. AB - The World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza (WHO CCs) tested 13,312 viruses collected by WHO recognized National Influenza Centres between May 2014 and May 2015 to determine 50% inhibitory concentration (IC50) data for neuraminidase inhibitors (NAIs) oseltamivir, zanamivir, peramivir and laninamivir. Ninety-four per cent of the viruses tested by the WHO CCs were from three WHO regions: Western Pacific, the Americas and Europe. Approximately 0.5% (n = 68) of viruses showed either highly reduced inhibition (HRI) or reduced inhibition (RI) (n = 56) against at least one of the four NAIs. Of the twelve viruses with HRI, six were A(H1N1)pdm09 viruses, three were A(H3N2) viruses and three were B/Yamagata-lineage viruses. The overall frequency of viruses with RI or HRI by the NAIs was lower than that observed in 2013-14 (1.9%), but similar to the 2012-13 period (0.6%). Based on the current analysis, the NAIs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections. PMID- 27265624 TI - High-contrast grating resonators for label-free detection of disease biomarkers. AB - A label-free optical biosensor is described that employs a silicon-based high contrast grating (HCG) resonator with a spectral linewidth of ~500 pm that is sensitive to ligand-induced changes in surface properties. The device is used to generate thermodynamic and kinetic data on surface-attached antibodies with their respective antigens. The device can detect serum cardiac troponin I, a biomarker of cardiac disease to 100 pg/ml within 4 mins, which is faster, and as sensitive as current enzyme-linked immuno-assays for cTnI. PMID- 27265625 TI - Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form. AB - Gap junctions (GJs) are aqueous channels that allow cells to communicate via physiological signals directly. The role of gap junctional connectivity in determining single-cell functions has long been recognized. However, GJs have another important role: the regulation of large-scale anatomical pattern. GJs are not only versatile computational elements that allow cells to control which small molecule signals they receive and emit, but also establish connectivity patterns within large groups of cells. By dynamically regulating the topology of bioelectric networks in vivo, GJs underlie the ability of many tissues to implement complex morphogenesis. Here, a review of recent data on patterning roles of GJs in growth of the zebrafish fin, the establishment of left-right patterning, the developmental dysregulation known as cancer, and the control of large-scale head-tail polarity, and head shape in planarian regeneration has been reported. A perspective in which GJs are not only molecular features functioning in single cells, but also enable global neural-like dynamics in non-neural somatic tissues has been proposed. This view suggests a rich program of future work which capitalizes on the rapid advances in the biophysics of GJs to exploit GJ-mediated global dynamics for applications in birth defects, regenerative medicine, and morphogenetic bioengineering. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 643-673, 2017. PMID- 27265626 TI - Hematological aspects of Crimean-Congo hemorrhagic fever. AB - Crimean-Congo hemorrhagic fever (CCHF) is an acute tick-borne viral disease transmitted to humans by Hyalomma ticks or by direct contact with the blood of infected humans or domestic animals. In certain areas of the world, including Africa, Asia, South East Europe and Middle East, sporadic cases or outbreaks of CCHF have been reported. During the last six-year period from 2003 to 2009, CCHF has also occurred endemically in Turkey, particularly during spring and summer, with a case-fatality rate of approximately 5%. The disease is characterized by acute fever, nausea, vomiting, headache, myalgia, elevated liver enzymes and hemorrhagic manifestations ranging from mucocutaneous bleeding to life threatening massive hemorrhage with disseminated intravascular coagulation (DIC) and hemophagocytosis. As with other viral hemorrhagic diseases, activation of lymphocytes, monocytes, macrophages and oversecretion of cytokines play a pivotal role in the pathogenesis and prognosis of CCHF. Recently an increasing number of publications on CCHF have been emerging in the literature, majority of which have been written by infection specialists. In this article, recent literature on CCHF has been reviewed, with particular emphasis on hematological manifestations, pathogenesis and therapeutic approaches in CCHF from the hematologist's point of view. PMID- 27265627 TI - Cap +1 mutation; an unsuspected cause of beta thalassaemia transmission in Pakistan. AB - OBJECTIVE: Thalassemia is one of the most common genetic disorders worldwide. Cap +1 mutation which causes 'silent beta thalassemia' is present around all ethnic groups of Pakistan. This study was designed to detect the frequency of Cap+1 mutation in Pakistani Population. METHODS: Molecular genetic for Cap+1 beta thalassemic mutation was done by extracting DNA from whole blood by using Genomic DNA Purification Kit (Gentra system USA). Amplification Refractory Mutation System (ARMS) primers were designed for detection of normal and mutant DNA. Basic hematological parameters were performed by using automated analyzer (Sysmex KX 21). Cellulose acetate hemoglobin electrophoresis was done by using semi automated technique (INTERLAB Roma Microtech Series Electrophoresis system 4.23). RESULTS: The frequency of Cap+1 mutation was observed 5% (10/200) in targeted thalassemic families (having patients with beta-thalassemia intermedia) while its frequency was observed 2% (12/600) in total thalassemic genes in Pakistani population. CONCLUSION: Cap+1 (A-C) is a silent mutation and it has very minimum effect on beta globin synthesis because of which it produces very less clinical severity and certain important laboratory diagnostic tests like basic hematological parameters and Hb A2 levels are also remain in normal range. Therefore individuals with Cap+1 mutation may produce children with beta thalassemia intermedia if they marry an individual with beta-thalassemia minor. Cap+1 (A-C) mutation is an unsuspected cause of beta thalassemia transmission in Pakistani population. This mutation can identify at molecular level. As this molecular defect is difficult to diagnose in Laboratory with routine laboratory tests because of that it has become a serious hindrance for thalassemia prevention program in Pakistan. PMID- 27265628 TI - Incidence of anti-heparin/platelet factor 4 antibodies and heparin-induced thrombocytopenia in medical patients. AB - OBJECTIVE: Heparin-induced thrombocytopenia (HIT) is a life threatening complication of heparin therapy, causing thrombosis. The aim of our study was to find out the frequencies of HIT antibody seroconversion and clinical HIT in Turkish medical patients on different forms of heparins. METHODS: Our study included 61 patients who were on unfractionated heparin (UFH) (n: 37) and low molecular weight heparin (LMWH) (n: 24) therapies. The frequency of HIT antibody formation was determined by means of antigenic (ELISA), and functional assays (serotonin release assay-SRA). RESULTS: The seroconversion rates in UFH and LMWH groups were found to be 18.9% and 4.1% (ELISA), and 8.1% and 4.1% (SRA), respectively. One patient (2.1%) on UFH therapy developed deep vein thrombosis. No thromboembolic event was observed in patients taking LMWH. CONCLUSION: Seroconversion rates by means of antigenic and functional assays and clinical HIT were more common in patients on UFH than patients on LMWH therapy. PMID- 27265629 TI - Hyperbaric Oxygen: an important treatment modality in severe hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation. AB - OBJECTIVE: Hemorrhagic cystitis (HC) is a generally self-limited complication of hematopoietic stem cell transplantation (HSCT). It may occur in the early or late posttransplant period and can promote sometimes severe morbidity. We analyzed our data regarding HC in allogeneic HSCT patients in order to establish the efficacy of hyperbaric oxygen (HBO) therapy in severe HC and to document the main problems during its use. METHODS: Between March 1993 and August 2006, 161 patients received allogeneic HSCT. Mesna, hyperhydration and forced diuresis were used as early HC prophylaxis of cyclophosphamide-induced HC. However, HC was diagnosed in 49 of the 161 recipients and 17 of them were considered as severe HC. We analyzed their data retrospectively. RESULTS: Forced diuresis with hyperhydration (up to 8 L/day) and transfusion support to maintain a platelet count above 30x109/L were sufficient in 10 of the 17 patients with severe HC. Alternative therapies used included intravesical irrigation with formalin and prostaglandin (PG)F2 alpha and HBO, and HBO appeared to be the most useful among them. CONCLUSION: We conclude that HBO offers a noninvasive therapeutic alternative in the management of intractable HC in the HSCT setting. PMID- 27265630 TI - The effects of low electromagnetic field and lead acetate combination on some hemato-biochemical and immunotoxicological parameters in mice. AB - OBJECTIVE: The present study was carried out to investigate the potential effects of extremely low-frequency electromagnetic fields (ELF-EMF) and lead acetate on some hemato-biochemical, immune and pathologic variables in mice. METHODS: A total of 90 female mice were equally divided into six groups. (Gp. 1) kept as control, (Gp. 2) exposed to EMF of 2 millitesla (mT) intensity and 50 Hz frequency (4h/day) for 30 days, (Gps. 3 and 4) were administered lead acetate orally at doses 1 and 5 mg/kg BW, respectively for 30 days. The last 2 groups (5, 6) were exposed to EMF- lead combination for the same period. RESULTS: EMF exposure induced a significant increase in RBCs (p<0.001), WBCs (p<0.01) and platelets (p<0.001) counts, compared to control. However, anemia and leukopenia were recorded with oral administration of Pb acetate. The phagocytosis % and phagocytic index were significantly (p<0.05) increased in mice exposed to EMF for 30 days, but decreased (p<0.01) in the animals given the highest dose of lead. Comparing to unexposed mice, significant variation in biochemical parameters (glucose, enzymes, and protein profiles) were noticed. Combined lead and EMF treatments had antagonizing effect on some previous parameters, whereas mice given the highest dose of lead with EMF aggravated hemato-biochemical and pathological findings. CONCLUSION: We concluded that combined exposure to ELF-EMF and Pb acetate produced significant changes in the hemato-biochemical and immune parameters which were both real and inconsistent. PMID- 27265631 TI - Invasive fungal diseases in children with hematologic disorders. AB - OBJECTIVE: Fungal infection is a significant problem, causing of infective deaths of leukemic patients. The situation in developing countries is not well documented. The purpose of this study was characterizing IFD by analyzing data retrospectively to determine the incidence, predisposing factors, diagnostic methods, efficacy of treatment, and the outcome in pediatric patients with hematological disorders. METHODS: There were 160 children with leukemia (22 AML, 129 ALL) and 9 with aplastic anemia (AA). The diagnostic criteria for IFD were defined according to the EORTC/MSG, 2008. IFD was classified as proven or probable. Empiric antifungal treatment with L-AmB was commenced by day 5-7 of persistent fever. Patients with invasive aspergillosis (IA) who were refractory to primary treatment were commenced on voriconazole (VCZ). Salvage therapy as combination of VCZ and caspofungin was given to those with progressive infection. RESULTS: The incidence of IFD was found 23 (14.3%). 19 with leukemia (14 ALL, 5 AML) and 4 with aplastic anemia were diagnosed as IFD. IA was the dominant cause of infection (n=17) and the rest (n: 6) had candidiasis. Ten children had "proven" infection and 13 children were defined as "probable". The most frequent site of infection was lungs. In our series, the most frequently used diagnostic methods were clinical findings (100%) and radiologic methods (84%). The success rate of treatment for candidiasis and IA were found 60%, 71% respectively. IFD related death rate was found 30%. CONCLUSION: IFD is still a major morbidity and mortality reason in children with hematologic disorders. However, the availability of new antifungal treatments and diagnostic tests will improve the survival rates in these children. PMID- 27265632 TI - The levels of nitric oxide in megaloblastic anemia. AB - OBJECTIVE: The purpose of this study was to investigate the relationship between nitric oxide degradation products (nitrate and nitrite) levels and megaloblastic anemia which is treated with cyalocobalamin. METHODS: A total of 30 patients with megaloblastic anemia (16 Male, 14 Female) were included in the study. Cyanocobalamin was administered (1.000 ug/day intramuscularly) until the reticulocyte crisis occurred to the normal range. The control group consisted of 30 healthy subjects (15 Male, 15 Female). Nitric oxide levels were measured before treatment and compared with the values obtained during peak reticulocyte count. RESULTS: Plasma direct nitrite, total nitrite and nitrate levels were 24,86+/-3,87, 60.56+/-7,01 and 36,02+/-5,24 in before treatment versus 15,48+/ 3,05, 38,92+/-6,44 and 22,77+/-6,04 MUmol/dl in after treatment, respectively. Plasma direct nitrite, total nitrite and nitrate levels were significantly lower in after treatment compared with the before treatment (p<0.001). CONCLUSION: Nitric oxide levels are seen to increase in megaloblastic anemia. This study suggested that abnormalities in the nitric oxide levels in megaloblastic anemia are restored by vitamin B12 replacement therapy. PMID- 27265633 TI - Simultaneous occurrence of Kaposi's sarcoma and nodular lymphocyte predominant subtype of Hodgkin's lymphoma in the same lymph node. AB - Many cases have been established with coexisting Kaposi's sarcoma (KS) and classical Hodgkin's Lymphoma (C-HL) in the same lymph node. But composite presentation of KS and Nodular Lymphocyte Predominant subtype of Hodgkin's lymphoma (NLPHL) in the same lymph node has not been described yet. KS is related to immunodeficiency most frequently due to human immunodeficiency virus (HIV) infection or immunosupression by other reasons. Our case presented here was not related to any immunodeficiency status. Besides of being the first case of composite KS and NLPHL in the same lymph node, it was also unusual with the indolent behaviour of the NLPHL without any therapy for 8 years follow up and primary lymph node presentation of KS without cutaneous involvement. PMID- 27265634 TI - Acute massive myelofibrosis with acute lymphoblastic leukemia. AB - Acute myelofibrosis is characterized by pancytopenia of sudden onset, megakaryocytic hyperplasia, extensive bone marrow fibrosis, and the absence of organomegaly. Acute myelofibrosis in patients with acute lymphoblastic leukemia is extremely rare. We report a 4-year-old boy who was diagnosed as having acute massive myelofibrosis and acute lymphoblastic leukemia. Performing bone marrow aspiration in this patient was difficult (a "dry tap"), and the diagnosis was established by means of a bone marrow biopsy and immunohistopathologic analysis. The prognostic significance of acute myelofibrosis in patients with acute lymphoblastic leukemia is not clear. PMID- 27265635 TI - Intestinal mucus accumulation in a child with acute myeloblastic leukemia. AB - Intestinal mucus accumulation is a very rare situation observed in some solid tumors, intestinal inflammation, mucosal hyperplasia, elevated intestinal pressure, and various other diseases. However, it has never been described in acute myeloblastic leukemia. The pathogenesis of intestinal mucus accumulation is still not clear. Here, we report a 14-year-old girl with acute myeloblastic leukemia and febrile neutropenia in addition to typhlitis. She was also immobilized due to joint contractures of the lower extremities and had intestinal mucus accumulation, which was, at first, misdiagnosed as intestinal parasitosis. We speculate that typhlitis, immobilization and decreased intestinal motility due to usage of antiemetic drugs might have been the potential etiologic factors in this case. However, its impact on prognosis of the primary disease is unknown. PMID- 27265636 TI - Recurrent bruising of lower eyelids: a presenting symptom of neuroblastoma in a child. PMID- 27265637 TI - Treatment of primary myelofibrosis. PMID- 27265638 TI - Megadose methylprednisolone for granulocytic sarcoma. PMID- 27265639 TI - Premarital screening in Mugla Region of Turkey. PMID- 27265640 TI - Chemotherapeutic trial for acute leukemia in Iraq. PMID- 27265643 TI - Transcatheter Aortic Valve Replacement: A Solution for the Young, Inoperable and Regurgitant. AB - Transcatheter aortic valve replacement (TAVR) has become an established treatment for patients with severe aortic stenosis and high surgical risk. Ten years of technological advances in valve structure and delivery systems alongside growing operator and centre experience has opened TAVR implantation to an increasingly broad range of patients. The extension to off-label use however needs careful consideration and monitoring. Through discussion of our case involving an inoperable 24-year-old male with severe aortic regurgitation (AR), we highlight the need for an experienced and multidisciplinary team, together with early and extensive patient and family disclosure and engagement, prior to considering any off-label application of TAVR. PMID- 27265642 TI - Novel Proton Conducting Solid Bio-polymer Electrolytes Based on Carboxymethyl Cellulose Doped with Oleic Acid and Plasticized with Glycerol. AB - The plasticized solid bio-polymer electrolytes (SBEs) system has been formed by introducing glycerol (Gly) as the plasticizer into the carboxymethyl cellulose (CMC) doped with oleic acid (OA) via solution casting techniques. The ionic conductivity of the plasticized SBEs has been studied using Electrical Impedance Spectroscopy. The highest conductivity achieved is 1.64 * 10(-4) S cm(-1) for system containing 40 wt. % of glycerol. FTIR deconvolution technique had shown that the conductivity of CMC-OA-Gly SBEs is primarily influenced by the number density of mobile ions. Transference number measurement has shown that the cation diffusion coefficient and ionic mobility is higher than anion which proved the plasticized polymer system is a proton conductor. PMID- 27265644 TI - Myocardial Infarction in the "Young": Risk Factors, Presentation, Management and Prognosis. AB - Myocardial infarction (MI) in the "young" is a significant problem, however there is scarcity of data on premature coronary heart disease (CHD) and MI in the "young". This may lead to under-appreciation of important differences that exist between "young" MI patients versus an older cohort. Traditional differences described in the risk factor profile of younger MI compared to older patients include a higher prevalence of smoking, family history of premature CHD and male gender. Recently, other potentially important differences have been described. Most "young" MI patients will present with non-ST elevation MI but the proportion presenting with ST-elevation MI is increasing. Coronary angiography usually reveals less extensive disease in "young" MI patients, which has implications for management. Short-term prognosis of "young" MI patients is better than for older patients, however contemporary data raises concerns regarding longer-term outcomes, particularly in those with reduced left ventricular systolic function. Here we review the differences in rate, risk factor profile, presentation, management and prognosis between "young" and older MI patients. PMID- 27265641 TI - Dynamic Changes in High-Sensitivity Cardiac Troponin I Are Associated with Dynamic Changes in Sum Absolute QRST Integral on Surface Electrocardiogram in Acute Decompensated Heart Failure. AB - BACKGROUND: A three-dimensional electrocardiographic (ECG) metric, the sum absolute QRST integral (SAI QRST), predicts ventricular arrhythmias in heart failure (HF) patients with implantable cardioverter defibrillator and mechanical response to cardiac resynchronization therapy. We hypothesized that there is an association between patient-specific changes in SAI QRST and myocardial injury as measured by high-sensitivity troponin I (hsTnI). METHODS: Sum absolute integral QRST on resting 12-lead ECG and hsTnI were measured simultaneously, every 3 hours, and during 12-hour observation period in a prospective cohort of emergency department patients (n = 398; mean age 57.8 +/- 13.2 years; 54% female, 64% black), diagnosed with acute coronary syndrome (ACS, n = 28), acutely decompensated HF (acute decompensated heart failure, n = 35), cardiac non-ACS (n = 19), or noncardiac condition (n = 316). Random-effects linear regression analysis assessed the association of SAI QRST and myocardial injury, with adjustment for demographics (age, sex, race), prevalent cardiovascular disease (myocardial infarction, history of revascularization, stroke, and HF), risk factors (diabetes, smoking, hypercholesterolemia, hypertension, and cocaine use), and left bundle branch block. RESULTS: Within the entire cohort, SAI QRST decreased by 3 (95%CI -5 to -1) mV*ms every 3 hours. A 10-fold increase in hsTnI was associated with a 7.7 (0.6-14.9) mV*ms increase in SAI QRST. In the subgroup of acutely decompensated HF patients (n = 35), a 10-fold increase in hsTnI was associated with a 61.0 (5.9-116.1) mV*ms increase in SAI QRST. CONCLUSION: Patient-specific time-varying changes in the surface ECG scalar measure of global electrical heterogeneity, as measured by SAI QRST, and in myocardial injury as measured by hsTnI, are independently and directly associated with each other, likely reflecting a common underlying mechanism. PMID- 27265646 TI - Impact by Citations and Downloads: What are Heart, Lung and Circulation's Top 25 Articles of All Time? PMID- 27265645 TI - Routine Use of Fluoroscopic-Guided Femoral Arterial Puncture to Minimise Vascular Complication Rates in CTO Intervention: Multi-centre UK Experience. AB - BACKGROUND: Chronic total occlusion (CTO) revascularisation has a crucial role in contemporary percutaneous coronary intervention (PCI). Procedural success is influenced by disease complexity, calcific burden and patient characteristics but has substantially improved with the implementation of novel hybrid strategies. However, vascular-access related complications remain a cause of morbidity and mortality. This study aimed to assess the effectiveness of fluoroscopic-guided femoral arterial puncture to minimise this risk during CTO PCI. METHODS: Standardised data were retrospectively collected from four high-volume UK CTO centres between September 2011 and November 2013. Demographic, clinical and procedural data (vascular access site, sheath size, anticoagulation use) was collated. The anatomical location of the femoral puncture in relation to the femoral bifurcation, femoral head position and inferior epigastric artery were recorded. Adverse events related to vascular access were documented. RESULTS: A total of 528 patients were included (676 femoral punctures) with the majority being male (n=432, 81.8%). Large sheaths (8F) were used in 81.2% of cases. Fluoroscopy-enabled punctures were made in the 'safe zone' in over > 93% of cases. Vascular closure devices (VCD) were used in 88.3% of cases. The adverse event rate per puncture was 0.89%. CONCLUSIONS: This study demonstrates an extremely low incidence of vascular-access complications in CTO PCI when fluoroscopic guidance is used to obtain femoral arterial access by default radial operators. PMID- 27265647 TI - Long-Term Effectiveness of the Pedicled Buccal Fat Pad in the Closure of a Large Oroantral Fistula. AB - PURPOSE: This study evaluated the long-term effectiveness of the pedicled buccal fat pad (BFP) in the closure of a large oroantral fistula (OAF). MATERIALS AND METHODS: Twenty-five consecutive patients with OAFs larger than 5 mm were treated with a pedicled BFP. They were followed clinically and radiographically for 10 years after surgery to monitor the durability and effectiveness of the pedicled BFP in the closure of the OAF. RESULTS: The procedure was successful in all patients. The healing process was satisfactory, with no breakdown or liquefaction necrosis postoperatively. No complications were observed during the follow-up period. CONCLUSIONS: The results of this study support the view that the use of the pedicled BFP is a durable, straightforward, convenient, and reliable method for the treatment of a large OAF. PMID- 27265648 TI - Who is innocent in authorship misconduct? PMID- 27265649 TI - Systematics of the Artiodactyla of China in the 21(st) century. AB - In this paper, I have introduced the concept of the Evolutionary Species, and shown how it affects the taxonomy of the Artiodactyla of China. The "traditional" taxonomy of the Artiodactyla, which has remained almost unchanged for 100 years, relies on ill-formulated notions of species and subspecies, only slightly modified by the population-thinking of the 1930s. Species are populations (or metapopulations) differentiated by the possession of fixed heritable differences from other such populations (or metapopulations). In the Artiodactyla, there are many more species than "traditionally" recognised; this is by no means a drawback, as it enables the units of biodiversity to be identified in a testable fashion, and brings the taxonomy of large mammals into line with that long practised for small mammals. Species are likely to differentiate where there are natural gaps in the distribution of a genus, such as mountain blocks (for example in the genus Budorcas) or otherwise dissected habitat (for example in the genus Cervus). Natural hybridisation between distinct species is not an uncommon phenomenon, again illustrated well in the genus Cervus, where hybridisation between the elaphus and nippon groups occurs today and evidently occurred in the past, as shown by the distribution of mtDNA. PMID- 27265650 TI - Comparative transcriptome analysis on the alteration of gene expression in ayu (Plecoglossus altivelis) larvae associated with salinity change. AB - Ayu (Plecoglossus altivelis) fish, which are an amphidromous species distributed in East Asia, live in brackish water (BW) during their larval stage and in fresh water (FW) during their adult stage. In this study, we found that FW-acclimated ayu larvae exhibited a slower growth ratio compared with that of BW-acclimated larvae. However, the mechanism underlying FW acclimation on growth suppression is poorly known. We employed transcriptome analysis to investigate the differential gene expression of FW acclimation by RNA sequencing. We identified 158 upregulated and 139 downregulated transcripts in FW-acclimated ayu larvae compared with that in BW-acclimated larvae. As determined by Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway mapping, functional annotation of the genes covered diverse biological functions and processes, and included neuroendocrinology, osmotic regulation, energy metabolism, and the cytoskeleton. Transcriptional expression of several differentially expressed genes in response to FW acclimation was further confirmed by real-time quantitative PCR. In accordance with transcriptome analysis, iodothyronine deiodinase (ID), pro-opiomelanocortin (POMC), betaine homocysteine S-methyltransferase 1(BHMT), fructose-bisphosphate aldolase B (aldolase B), tyrosine aminotransferase (TAT), and Na(+)-K(+) ATPase (NKA) were upregulated after FW acclimation. Furthermore, the mRNA expressions of b-type natriuretic peptide (BNP) and transgelin were downregulated after FW acclimation. Our data indicate that FW acclimation reduced the growth rate of ayu larvae, which might result from the expression alteration of genes related to endocrine hormones, energy metabolism, and direct osmoregulation. PMID- 27265651 TI - Expression analysis of eight amphioxus genes involved in the Wnt/beta-catenin signaling pathway. AB - The Wnt/beta-catenin signaling pathway plays a crucial role in the embryonic development of metazoans. Although the pathway has been studied extensively in many model animals, its function in amphioxus, the most primitive chordate, remains largely uncharacterized. To obtain basic data for functional analysis, we identified and isolated seven genes (Lrp5/6, Dvl, APC, CkIalpha, CkIdelta, Gsk3beta, and Gro) of the Wnt/beta-catenin signaling pathway from the amphioxus (Branchiostoma floridae) genome. Phylogenetic analysis revealed that amphioxus had fewer members of each gene family than that found in vertebrates. Whole-mount in situ hybridization showed that the genes were maternally expressed and broadly distributed throughout the whole embryo at the cleavage and blastula stages. Among them, Dvl was expressed asymmetrically towards the animal pole, while the others were evenly distributed in all blastomeres. At the mid-gastrula stage, the genes were specifically expressed in the primitive endomesoderm, but displayed different patterns. When the embryo developed into the neurula stage, the gene expressions were mainly detected in either paraxial somites or the tail bud. With the development of the embryo, the expression levels further decreased gradually and remained only in some pharyngeal regions or the tail bud at the larva stage. Our results suggest that the Wnt/beta-catenin pathway might be involved in amphioxus somite formation and posterior growth, but not in endomesoderm specification. PMID- 27265652 TI - Expression levels of GSTA2 and APOD genes might be associated with carotenoid coloration in golden pheasant (Chrysolophus pictus) plumage. AB - Carotenoids, which generate yellow, orange, and red colors, are crucial pigments in avian plumage. Investigations into genes associated with carotenoidbased coloration in avian species are important; however, such research is difficult because carotenoids cannot be synthetized in vertebrates as they are only derived from dietary sources. Here, the golden pheasant (Chrysolophus pictus) was used as a model in analysis of candidate gene expression profiles implicated in carotenoid binding and deposition. Using mass and Raman spectrometry to confirm the presence of carotenoids in golden pheasant feathers, we found C40H54O and C40H56O2 in feathers with yellow to red colors, and in the rachis of iridescent feathers. The global gene expression profiles in golden pheasant skins were analyzed by RNA-seq and all six carotenoid binding candidate genes sequenced were studied by realtime PCR. StAR4, GSTA2, Scarb1, and APOD in feather follicles showed different expressions in red breast and orange nape feathers compared with that of iridescent mantle feathers. Further comparison of golden pheasant yellow rump and Lady Amherst's pheasant (Chrysolophus amherstiae) white nape feathers suggested that GSTA2 and APOD played a potential role in carotenoid-based coloration in golden pheasant. PMID- 27265654 TI - Conservation education and habitat restoration for the endangered Sagalla caecilian (Boulengerula niedeni) in Sagalla Hill, Kenya. AB - The Sagalla caecilian (Boulengerula niedeni) is an endangered amphibian endemic to Sagalla Hill in the Taita Hills. This burrowing worm-like species prefers soft soil with high moisture and organic matter. The major threats to the Sagalla caecilian are soil erosion caused by steep slopes, bare ground and water siphoning/soil hardening from exotic eucalyptus trees. The purpose of this study was to get a better understanding of the local people's attitude towards this species and how they can contribute to its continued conservation through restoration of its remaining habitat. In this study, it was found that 96% of Sagalla people are aware of the species, its habits and its association with soils high in organic matter. It was also found that 96% of Sagalla people use organic manure from cow dung in their farms. Habitat restoration through planting of indigenous plants was found to be ongoing, especially on compounds of public institutions as well as on private lands. Although drought was found to be a challenge for seedlings development especially on the low elevation sites, destruction by livestock especially during the dry season is also a major threat. In this study, it was recommended that any future habitat restoration initiative should include strong chain-link fencing to protect the seedlings from livestock activity. Recognizing that the preferred habitats for the species are in the valleys, systematic planting of keystone plant species such as fig trees (Ficus) creates the best microhabitats. These are better than general woodlots of indigenous trees. PMID- 27265653 TI - Effects of forest fragmentation on nocturnal Asian birds: A case study from Xishuangbanna, China. AB - Owls have the potential to be keystone species for conservation in fragmented landscapes, as the absence of these predators could profoundly change community structure. Yet few studies have examined how whole communities of owls respond to fragmentation, especially in the tropics. When evaluating the effect of factors related to fragmentation, such as fragment area and distance to the edge, on these birds, it is also important in heterogeneous landscapes to ask how 'location factors' such as the topography, vegetation and soil of the fragment predict their persistence. In Xishuangbanna, southwest China, we established 43 transects (200 m*60 m) within 20 forest fragments to sample nocturnal birds, both visually and aurally. We used a multimodel inference approach to identify the factors that influence owl species richness, and generalized linear mixed models to predict the occurrence probabilities of each species. We found that fragmentation factors dominated location factors, with larger fragments having more species, and four of eight species were significantly more likely to occur in large fragments. Given the potential importance of these birds on regulating small mammal and other animal populations, and thus indirectly affecting seed dispersal, we suggest further protection of large fragments and programs to increase their connectivity to the remaining smaller fragments. PMID- 27265655 TI - Interspecific variation of thermoregulation between small migratory and resident passerines in Wenzhou. AB - Physiological adaptation arises from several fundamental sources of phenotypic variation. Most analyses of metabolic adaptation in birds have focused on the basal metabolic rate (BMR), the lower limit of avian metabolic heat production. In this study, we investigated thermoregulation in three passerine species; the yellow-billed grosbeak Eophona migratoria, white-rumped munia Lonchura striata and black-throated bushtit Aegithalos concinnus, in Wenzhou, China. Metabolic rate was measured using the closed-circuit respirometer containing 3.5 L animal chambers. Body temperature (Tb) was measured during metabolic measurements using a lubricated thermocouple. The minimum thermal conductance of these species was calculated by measuring their Tb and metabolic rates. The yellow-billed grosbeak remained largely normothermic, and the white-rumped munia and black-throated bushtit exhibited variable Tb at ambient temperatures (Ta). Mean metabolic rates within thermal neutral zone were 2.48+/-0.09 O2(mL)/g/h for yellow-billed grosbeaks, 3.44+/-0.16 O2(mL)/g/h for white-rumped munias, and 3.55+/-0.20 O2(mL)/g/h for black-throated bushtits, respectively. Minimum thermal conductance of yellow-billed grosbeak, white-rumped munia and black-throated bushtit were 0.13+/-0.00, 0.36+/-0.01, and 0.37+/-0.01 O2(mL)/g/h/C, respectively. The ecophysiological characteristics of these species were:(1) the yellowbilled grosbeak had relatively high Tb and BMR, a low lower critical temperature and thermal conductance, and a metabolic rate that was relatively insensitive to variation in Ta; all of which are typical of cold adapted species and explain its broader geographic distribution; (2) the white-rumped munia and blackthroated bushtit had high thermal conductance, lower critical temperature, and relatively low BMR, all which are adapted to warm environments where there is little selection pressure for metabolic thermogenesis. Taken together, these data illustrate small migratory and resident passerines that exhibit the different characteristics of thermoregulation. PMID- 27265656 TI - Morphology and molecular phylogeny of two colepid species from China, Coleps amphacanthus Ehrenberg, 1833 and Levicoleps biwae jejuensis Chen et al., 2016 (Ciliophora, Prostomatida). AB - Two colepid ciliates, Coleps amphacanthus Ehrenberg, 1833 and Levicoleps biwae jejuensis Chen et al., 2016, were first recorded in China. Their living morphology, infraciliature and small subunit (SSU) rRNA gene sequences were determined using standard methods. The improved diagnosis of Coleps amphacanthus is as follows:cell size about 100*50 MUm in vivo, barrel-shaped; 22-28 ciliary rows each composed of about 14-21 monokinetids and two perioral dikinetids; 5-10 caudal cilia; and one terminal contractile vacuole. Levicoleps biwae jejuensis was also investigated, with an improved diagnosis given based on previous and present work. The phylogenetic analyses based on SSU rRNA gene sequences revealed that all Coleps species were grouped together, except for Coleps amphacanthus, which was grouped into a clade of the genus Levicoleps. PMID- 27265658 TI - Recent advances in diagnosis, prognosis and biology of small B cell lymphomas. PMID- 27265657 TI - Range extension of Lepidocephalichthys alkaia (Teleostei: Cobitidae) and notes on its sexual dimorphism. AB - The natural distributional range of the cobitid loach Lepidocephalichthys alkaia is extended into Yunnan Province, China. The modified sexually dimorphic pectoral fin in males of L. alkaia is described. PMID- 27265659 TI - Effects of sub-acute exposure to magnetic field on blood hematological and biochemical parameters in female rats. AB - The present work was undertaken in order to investigate the effects of magnetic field (MF) on hematopoiesis and fuel metabolites in female rats. At thermoneutrality (25 degrees C), the exposition of rats 1 hour/day for 10 consecutive days to a MF of 128 mT (m Tesla) induced an increase in hematocrit and hemoglobin compared to controls. Exposure to MF also induced an increase in blood glucose levels but had no effect on triglyceride concentrations. Moreover, serum alanine aminotransferase activity remained unchanged in treated rats, while aspartate aminotransferase and lactate dehydrogenase activities increased by about 22% and 33%, respectively, following MF exposure. It was concluded that sub acute exposure to MF induced elevations in hematocrit, hemoglobin, plasma fuel metabolites and tissue enzymes release within the blood. KEY WORDS: Magnetic field, hematology, glucose, triglycerides, plasma enzymes, rat. PMID- 27265660 TI - Retrospective analysis of results of short-term low dose interferon-alpha-2b combined with PUVA in the treatment of early stage mycosis fungoides. AB - Early-stage mycosis fungoides (MF) can be treated with different regimens such as oral photo-chemotherapy (Psoralen and UVA-PUVA). There have been some studies showing the effectiveness of combination of interferon (IFN) with PUVA. In this study, we aimed to evaluate retrospectively the patients with early-stage MF treated with IFN + PUVA. Six patients with the diagnosis of early stage (Ia-IIa) MF between June 2003 and May 2005 were enrolled in this study. IFN combined with PUVA was started and followed by IFN maintenance in complete response (CR) patients. Patients achieving CR were followed up at monthly intervals until relapse. Interferon-alpha-2b was administered at a dose of 3 MU 3 times a week and PUVA was applied 3 times a week. There were 4 female and 2 male patients, aged 32-75 years (mean 54.3 years). Four patients were at stage Ia, one patient at Ib and one patient at stage IIa according to TNM staging. Four of 6 patients (66%) achieved CR and 2 of 6 (33%) achieved partial response (PR). No grade 3-4 side effects due to IFN were detected, and no progression was observed during the treatment. All patients have been under treatment as planned. Low dose of IFN alpha-2b plus PUVA was found to be successful in achieving excellent clinical responses in patients with early-stage MF. This treatment modality was very well tolerated. PMID- 27265661 TI - Results of treatment of acute myeloid leukemia and myelodysplastic syndrome with etoposide, thioguanine, cytarabine (ETC) in elderly patients. AB - Treatment in elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains controversial, and results have been poor with most regimens. In order to study the efficacy of a new regimen in the treatment of these diseases in elderly patients assessed as not tolerating full scale anthracycline-containing intensive chemotherapy, 14 patients over 60 years were enrolled in our study. The median age was 69 years, range 60-85 years. Eight patients had MDS (one transformed to AML) and six had AML. Anthracycline-lacking therapy (ETC) consisted of etoposide 120 mg/m2 and thioguanine 100 mg/m2 p.o. twice daily on days 1-5 and cytarabine (araC) 40 mg/m2 s.c. on day 1. The preliminary results were as follows: 7 of the 14 patients (50%) achieved complete remission. The median survival was 10 months. Days spent at hospital were 28. Neutropenia was observed for 11 days and thrombocytopenia for 15 days. No severe infection was detected. Early death was observed in 2 (14%) of the patients. In conclusion, this novel treatment with a complete response of 50% appears to be a simple, safe, cost-effective form of therapy for elderly patients. PMID- 27265662 TI - Prothrombin G20210A and A19911G mutations in Turkish pediatric stroke patients. AB - Effects of PT A19911G polymorphism in Turkish pediatric stroke patients were investigated. The case-control study included 107 patients with cerebral infarct and 83 healthy unrelated controls. Distribution of PT A19911G and data on the combined effect of PT 19911G and PT 20210A alleles do not indicate that they constitute a risk in this group of patients. PMID- 27265663 TI - Hepatitis B&C virus infection in cases of Non-Hodgkin's lymphoma in Saudi Arabia. AB - We followed 565 male patients with non-Hodgkin's lymphoma (NHL) in two hospitals of Saudi Arabia. We investigated these cases for presence of hepatitis B virus (HBV) and hepatitis C virus (HCV) by determining the HBsAg and anti-HCV. Anti-HCV positive cases were confirmed by PCR. The NHL cases were classified on the basis of working formulation. The results of HBV and HCV in cases of NHL were compared with the prevalence of these viruses in healthy male blood donors. We found 11.2% of cases of NHL were positive for HBV and 16.1% for HCV, compared to 3.4% HBV and 2.9% HCV among blood donors. The highest numbers of cases (48.4% of HBV and 56% of HCV) were seen in the intermediate and low grade of NHL, respectively. Follicular small cleaved was the predominant type in both types of infection. The variation in prevalence of HBV and HCV in NHL from that of the general population was statistically significant (p<0.001). We observed that the background prevalence of HBV definitely affects the rate of infection in NHL, while infection of HCV in cases of NHL is independent of its background prevalence. PMID- 27265664 TI - Complete heart block in a neutropenic patient with invasive aspergillosis. AB - A patient with leukemia who developed complete heart block after the diagnosis of pulmonary aspergillosis is reported. The patient had probable invasive pulmonary aspergillosis with a sudden tachypnea, dyspnea, fever, bilateral pulmonary infiltrates and acute respiratory insufficiency after chemotherapy. On the sixth day of antifungal therapy, she developed complete atrioventricular block. Complete heart block has not been reported during liposomal amphotericin B (LAMB) therapy. Local or hematogenous involvement of the myocardium with aspergillosis may be the most likely explanation of the complete heart block. PMID- 27265665 TI - Simultaneous occurrence of multiple myeloma and acute myeloid leukemia. AB - Multiple myeloma and acute leukemia may sometimes occur in the same patient, usually in patients with myeloma who receive chemotherapy and subsequently develop acute leukemia. However, simultaneous occurrence of myeloma and acute leukemia on presentation is rare, with only a handful of such cases reported in the literature. PMID- 27265666 TI - Images in hematology. PMID- 27265667 TI - Hemoglobinopathies in Turkey. PMID- 27265668 TI - NMR absolute shielding scale and nuclear magnetic dipole moment of (207)Pb. AB - An absolute shielding scale is proposed for (207)Pb nuclear magnetic resonance (NMR) spectroscopy. It is based on ab initio calculations performed on an isolated tetramethyllead Pb(CH3)4 molecule and the assignment of the experimental resonance frequency from the gas-phase NMR spectra of Pb(CH3)4, extrapolated to zero density of the buffer gas to obtain the result for an isolated molecule. The computed (207)Pb shielding constant is 10 790 ppm for the isolated molecule, leading to a shielding of 10799.7 ppm for liquid Pb(CH3)4 which is the accepted reference standard for (207)Pb NMR spectra. The new experimental and theoretical data are used to determine MU((207)Pb), the nuclear magnetic dipole moment of (207)Pb, by applying the standard relationship between NMR frequencies, shielding constants and nuclear moments of two nuclei in the same external magnetic field. Using the gas-phase (207)Pb and (reference) proton results and the theoretical value of the Pb shielding in Pb(CH3)4, we find MU((207)Pb) = 0.59064 MUN. The analysis of new experimental and theoretical data obtained for the Pb(2+) ion in water solutions provides similar values of MU((207)Pb), in the range of 0.59000 0.59131 MUN. PMID- 27265669 TI - An isoflavone cladrin prevents high-fat diet-induced bone loss and inhibits the expression of adipogenic gene regulators in 3T3-L1 adipocyte. AB - OBJECTIVE: This study evaluates the effect of isoflavone cladrin on high-fat diet (HFD)-induced bone loss and adipogenesis. METHODS: Thirty-two 4-week-old male C57BL/6J mice were divided into four groups: a standard diet group, a HFD group and HFD group with cladrin (5 and 10 mg/kg per day orally) for 12 weeks. The effect of cladrin on bone micro-architecture, bone marrow cell lineages and hyperlipidaemia were assessed. For assessing anti-adipogenic activity of cladrin, 3T3-L1 cells were used. KEY FINDINGS: Cladrin attenuated HFD-induced hyperlipidaemia and bone loss by preserving bone micro-architecture and strength. Effect of cladrin was found at the level of bone marrow progenitor cells. Gene expression profile of cladrin-treated mice bone showed upregulation of osteoblast and downregulation of adipogenic transcription factors and increased OPG/RANKL ratio. Cladrin inhibited cellular lipid accumulation through downregulation of transcription factors such as PPAR-gamma and C/EBP-alpha and modulated the expression of major adipokines involved behind obesity stimulation without eliciting cell cytotoxicity in 3T3-L1 adipocytes. CONCLUSION: We conclude that cladrin may improve obesity-induced bone loss and hyperlipidaemia in mice fed HFD and adipogenesis in 3T3-L1 cells by modifying adipokines and could offer clinical benefits as a supplement to treat obesity-induced disorders. PMID- 27265670 TI - Sustaining a Global Social Network: a quasi-experimental study. AB - AIM: To examine the longer term impact on the social network of participating nurses in the Global Nursing Leadership Institute (GNLI2013) through using differing frequencies of follow-up to assess impact on maintenance of network cohesion. BACKGROUND: Social network analysis is increasingly been used by nurse researchers, however, studies tend to use single point-in-time descriptive methods. METHOD: This study utilizes a repeated measures, block group, control intervention, quasi-experimental design. Twenty-eight nurse leaders, competitively selected through a double-blind peer review process, were allocated to five action learning-based learning groups. Network architecture, measures of cohesion and node degree frequency were all used to assess programme impact. RESULTS: The programme initiated and sustained connections between nurse leaders drawn from a geographically dispersed heterogeneous group. Modest inputs of two to three e-mails over a 6-month period seem sufficient to maintain connectivity as indicated by measures of network density, diameter and path length. LIMITATIONS: Due to the teaching methodology used, the study sample was relatively small and the follow-up data collection took place after a relatively short time. Replication and further cohort data collection would be advantageous. CONCLUSIONS AND POLICY IMPLICATIONS: In an era where many policy solutions are being debated and initiated at the global level, action learning leadership development that utilizes new technology follow-up appears to show significant impact and is worthy of wider application. The approach warrants further inquiry and testing as to its longer term effects on nursing's influence on policy formulation and implementation. PMID- 27265671 TI - Estimation of bladder contractility from intravesical pressure-volume measurements. AB - AIMS: To describe parameters from urodynamic pressure recordings that describe urinary bladder contractility through the use of principles of muscle mechanics. METHODS: Subtracted detrusor pressure and voided flow were recorded from patients undergoing filling cystometry. The isovolumetric increase of detrusor pressure, P, of a voluntary bladder contraction before voiding was used to generate a plot of (dP/dt)/P versus P. Extrapolation of the plot to the y-axis and the x-axis generated a contractility parameter, vCE (the maximum rate of pressure development) and the maximum isovolumetric pressure, P0 , respectively. Similar curves were obtained in ex vivo pig bladders with different concentrations of the inotropic agent carbachol and shown in a supplement. RESULTS: Values of vCE , but not P0 , diminished with age in female subjects. vCE was most significantly associated with the 20-80% duration of isovolumetric contraction t20-80 ; and a weaker association with maximum flow rate and BCI in women. P0 was not associated with any urodynamic variable in women, but in men was with t20-80 and isovolumetric pressure indices. CONCLUSIONS: The rate of isovolumetric subtracted detrusor pressure (t20-80 ) increase shows a very significant association with indices of bladder contractility as derived from a derived force-velocity curve. We propose that t20-80 is a detrusor contractility parameter (DCP). Neurourol. Urodynam. 36:1009-1014, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27265672 TI - Right Ventricular Function After Acute Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention (from the Glycometabolic Intervention as Adjunct to Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction III Trial). AB - Right ventricular (RV) dysfunction is a powerful risk marker after acute myocardial infarction (MI). Primary percutaneous coronary intervention (PCI) has markedly reduced myocardial damage of the left ventricle, but reliable data on RV damage using cardiac magnetic resonance imaging (MRI) are scarce. In a recent trial of patients with acute MI treated with primary PCI, in which the primary end point was left ventricular (LV) ejection fraction after 4 months measured with MRI, we conducted a prospectively defined substudy in which we examined RV function. RV ejection fraction (RVEF) and RV scar size were measured with MRI at 4 months. Tricuspid annular plane systolic excursion (TAPSE) and RV free wall longitudinal strain (FWLS) were assessed using echocardiography before discharge and at 4 months. We studied 258 patients without diabetes mellitus; their mean age was 58 +/- 11 years, 79% men and mean LV ejection fraction was 54 +/- 8%. Before discharge, 5.2% of patients had TAPSE <17 mm, 32% had FWLS > -20% and 11% had FWLS > -15%. During 4 months, TAPSE increased from 22.8 +/- 3.6 to 25.1 +/- 3.9 mm (p <0.001) and FWLS increased from -22.6 +/- 5.8 to -25.9 +/- 4.7% (p <0.001). After 4 months, mean RVEF on MRI was 64.1 +/- 5.2% and RV scar was detected in 5 patients (2%). There was no correlation between LV scar size and RVEF (p = 0.9), TAPSE (p = 0.1), or RV FWLS (p = 0.9). In conclusion, RV dysfunction is reversible in most patients and permanent RV ischemic injury is very uncommon 4 months after acute MI treated with primary PCI. PMID- 27265673 TI - Meta-Analysis of Usefulness of Percutaneous Left Ventricular Assist Devices for High-Risk Percutaneous Coronary Interventions. AB - High-risk percutaneous coronary intervention (PCI) is often offered to patients with extensive coronary artery disease, decreased left ventricular function, and co-morbid conditions that increase surgical risk. In these settings, percutaneous left ventricular assist devices (PVADs) can be used for hemodynamic support. To assess the effects of PVAD use on mortality, myocardial infarction, and complication rates in patients undergoing high-risk PCI, we systematically searched the electronic databases, MEDLINE, PUBMED, EMBASE, and Cochrane for prospective controlled trials and cohort studies of patients that received hemodynamic support with PVADs for high-risk PCI. The primary outcome measures were 30-day all-cause mortality, 30-day myocardial infarction rates, periprocedural major bleeding, and vascular complications. We included 12 studies with 1,346 participants who underwent Impella 2.5 L device placement and 8 cohort studies with 205 patients that received TandemHeart device for high-risk PCI. Short-term mortality rates were 3.5% and 8% and major bleeding rates were 7.1% and 3.6% with Impella and TandemHeart, respectively. Both devices are associated with comparable periprocedural outcomes in patients undergoing high-risk PCI. PMID- 27265675 TI - Prognostic Implications of Elevated Pulmonary Artery Pressure After ST-Segment Elevation Myocardial Infarction. AB - Elevated systolic pulmonary artery pressure (SPAP) after ST-segment elevation myocardial infarction (STEMI) has been associated with adverse outcome. However, little is known about the development of increased SPAP after STEMI treated with primary percutaneous coronary intervention. The aims of this study were to investigate the incidence and determinants of elevated SPAP (SPAP >=36 mm Hg at 12 months) after first STEMI and to analyze its prognostic implications. A total of 705 patients (60 +/- 12 years; 75% men; left ventricular ejection fraction [LVEF] 47 +/- 9%) with first STEMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was available at baseline and 12-month follow-up. Data on all-cause mortality were collected at long-term follow-up. Incident elevated SPAP was present in 5% (n = 38) of patients. Patients with incident elevated SPAP were older (66 +/- 12 vs 60 +/- 11 years, p = 0.001), had more systemic hypertension (58% vs 30%, p <0.001) and lower LVEF (43 +/- 9% vs 48 +/- 8%, p <0.001) than their counterparts. Left atrial volume was larger (23 +/- 11 vs 18 +/- 6 ml/m(2), p = 0.006), and moderate to severe mitral regurgitation was more prevalent in patients with incident elevated SPAP (16% vs 7%, p = 0.05). Independent correlates of incident elevated SPAP at 12-month follow-up were age (odds ratio [OR] 1.04, 95% CI 1.01 to 1.08, p = 0.01), hypertension (OR 2.52, 95% CI 1.23 to 5.14, p = 0.01), baseline LVEF (OR 0.94, 95% CI 0.90 to 0.98, p = 0.003), and baseline left atrial volume (OR 1.08, 95% CI 1.03 to 1.12, p = 0.001). Incident elevated SPAP was independently associated with all-cause mortality (hazard ratio 3.84, 95% CI 1.76 to 8.39, p = 0.001). In conclusion, although the incidence of elevated SPAP after STEMI is low, its presence is independently associated with increased risk of all-cause mortality at follow-up. PMID- 27265674 TI - Usefulness of the Sum Absolute QRST Integral to Predict Outcomes in Patients Receiving Cardiac Resynchronization Therapy. AB - Cardiac resynchronization therapy (CRT) reduces mortality and morbidity in selected patients with heart failure (HF), but up to 1/3 of patients are nonresponders. Sum absolute QRST integral (SAI QRST) recently showed association with mechanical response on CRT. However, it is unknown whether SAI QRST is associated with all-cause mortality and HF hospitalizations in patients undergoing CRT. The study population included 496 patients undergoing CRT (mean age 69 +/- 10 years, 84% men, 65% left bundle branch block [LBBB], left ventricular ejection fraction 23 +/- 6%, 63% ischemic cardiomyopathy). Preimplant digital 12-lead electrocardiogram was transformed into orthogonal XYZ electrocardiogram. SAI QRST was measured as an arithmetic sum of areas under the QRST curve on XYZ leads and was dichotomized based on the median value (302 mV ms). All-cause mortality served as the primary end point. A composite of 2-year all-cause mortality, heart transplant, and HF hospitalization was a secondary end point. Cox regression models were adjusted for known predictors of CRT response. Patients with preimplant low mean SAI QRST had an increased risk of both the primary (hazard ratio [HR] 1.8, 95% CI 1.01 to 3.2) and secondary (HR 1.6, 95% CI 1.1 to 2.2) end points after multivariate adjustment. SAI QRST was associated with secondary outcome in subgroups of patients with LBBB (HR 2.1, 95% CI 1.5 to 3.0) and with non-LBBB (HR 1.7, 95% CI 1.0 to 2.6). In patients undergoing CRT, preimplant SAI QRST <302 mV ms was associated with an increased risk of all-cause mortality and HF hospitalization. After validation in another prospective cohort, SAI QRST may help to refine selection of CRT recipients. PMID- 27265676 TI - Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy. AB - Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holter electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holter ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 +/- 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses >=3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter-defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holter ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with an implantable loop recorder. PMID- 27265678 TI - Characterization of methicillin resistant Staphylococcus aureus strains among inpatients and outpatients in a referral hospital in Tehran, Iran. AB - Methicillin resistant Staphylococcus aureus is one of the most common causes of a variety of infections ranging from wound infections to urinary tract infections (UTI) in hospital and community. In this study during 3 years we characterized the antibiotic resistance patterns of 491 hospital acquired MRSA and community associated MRSA strains by the guidelines of clinical and laboratory standard institute. A combination of high resolution PhP typing method and SCCmec typing were used for clonal dissemination of isolates. Among all 491 MRSA strains, diverse PhP types consisting of 29 common types (CTs) and 4 single types (STs) and also 2 different SCCmec types (III and IVa) were detected. In addition, 18 CTs were common among CA- and HA-MRSA strains and the presence of all 4 STs was limited to HA-MRSA strains. All isolates were resistant to penicillin and high level resistance was observed against ciprofloxacin, erythromycin, tobramycin and kanamycin and the rate of resistance to most of the antibiotic tested among HA MRSA was significantly higher than CA-MRSA isolates. Moreover, all isolates showed susceptibility to linezolid, vancomycin and quinupristin-dalfopristin and very low resistance to fusidic acid, nitrofurantoin and chloramphenicol were detected. Our findings illustrated the increasing rate of clonal dissemination and persistence of highly antibiotic resistant CA-MRSA strains in Tehran hospitals, and also indicated the important role of the hospitals as the reservoir of MRSA strains. PMID- 27265677 TI - Inhibitory effects of rHP-NAP IgY against Helicobacter pylori attachment to AGS cell line. AB - Helicobacter pylori is a major human pathogen related to gastric adenocarcinoma and gastroduodenal diseases. Treatment of H. pylori infections is complicated by the rise of antibiotic resistance, necessitating investigation of alternative therapies. One such alternative is passive immunization by oral administration of antibacterial immunoglobulin. In the present study, chicken immunoglobulin (IgY) was used for passive immunotherapy against a major virulence factor of H. pylori, namely recombinant HP-Nap protein. Recombinant HP-Nap was prepared and used to immunize hens. IgY was purified from the eggs by polyethylene glycol precipitation method with a total IgY-HP-NAP yield of 30 mg per egg. The inhibitory effect of specific IgY on H. pylori attachment was investigated in AGS cell line infected by the bacteria. The results demonstrate the potent effect of IgY- HP-NAP in inhibition of H. pylori attachment to the AGS cells. PMID- 27265679 TI - Population structure and antimicrobial profile of Staphylococcus aureus strains associated with bovine mastitis in China. AB - Staphylococcus aureus is a significant bacterial pathogen associated with bovine mastitis. The aim of the present study was to investigate and characterize of S. aureus strains isolated from the milk of cows suffering from mastitis in the mid east of China. Among the 200 milk samples analyzed, 58 were positive for S. aureus, of these isolates, 11 isolates were methicillin-resistant Staphylococcus aureus (MRSA). All of the 58 S. aureus strains were classified in agr group I, while seven different sequence type (ST) patterns were identified and among them the most common was ST630 followed by ST188. All of the S. aureus isolates belonging to ST630 were resistant to more than four antimicrobials, and 22.2% of isolates belonging to ST188 were resistant to eight antimicrobials. Interestingly, while strong biofilm producers demonstrated higher resistance to multiple antimicrobials, they exhibited lower intracellular survival rates. The results of this study illustrated the distribution, antimicrobial susceptibility profiles, genotype, and the ability of biofilm production and mammary epithelial cells invasion of these S. aureus isolates. This study can provide the basis for the development of a disease prevention program in dairy farms to reduce the potential risk in both animal and human health. PMID- 27265680 TI - A Comprehensive Investigation toward the Indicative Proteins of Bladder Cancer in Urine: From Surveying Cell Secretomes to Verifying Urine Proteins. AB - Urine is an ideal material to study the cancer-related protein biomarkers in bladder, whereas exploration to these candidates is confronting technique challenges. Herein, we propose a comprehensive strategy of searching the urine proteins related with bladder cancer. The strategy consists of three core combinations, screening the biomarker candidates in the secreted proteins derived from the bladder cancer cell lines and verifying them in patient urines, defining the differential proteins through two-dimensional electrophoresis (2DE) and isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC MS/MS, and implementing quantitative proteomics of profiling and targeting analysis. With proteomic survey, a total of 700 proteins were found with their abundance of secreted proteins in cancer cell lines different from normal, while 87 proteins were identified in the urine samples. The multiple reaction monitoring (MRM)-based quantification was adapted in verifying the bladder cancer related proteins in individual urine samples, resulting in 10 differential urine proteins linked with the cancer. Of these candidates, receiver operating characteristic analysis revealed that the combination of CO3 and LDHB was more sensitive as the cancer indicator than other groups. The discovery of the bladder cancer indicators through our strategy has paved an avenue to further biomarker validation. PMID- 27265681 TI - Degradable Zinc-Phosphate-Based Hierarchical Nanosubstrates for Capture and Release of Circulating Tumor Cells. AB - Circulating tumor cells (CTCs) play a significant role in cancer diagnosis and personalized therapy, and it is still a significant challenge to efficiently capture and gently release CTCs from clinical samples for downstream manipulation and molecular analysis. Many CTC devices incorporating various nanostructures have been developed for CTC isolation with sufficient capture efficiency, however, fabricating such nanostructured substrates often requires elaborate design and complicated procedures. Here we fabricate a degradable zinc-phosphate based hierarchical nanosubstrate (HZnPNS), and we demonstrate its excellent CTC capture performance along with effective cell-release capability for downstream molecular analysis. This transparent hierarchical architecture prepared by a low temperature hydrothermal method, enables substantially enhanced capture efficiency and convenient imaging. Biocompatible sodium citrate could rapidly dissolve the architecture at room temperature, allowing that 88 +/- 4% of captured cells are gently released with a high viability of 92 +/- 1%. Furthermore, antiepithelial cell adhesion molecule antibody functionalized HZnPNS (anti-EpCAM/HZnPNS) was successfully applied to isolate CTCs from whole blood samples of cancer patients, as well as release CTCs for global DNA methylation analysis, indicating it will serve as a simple and reliable alternative platform for CTC detection. PMID- 27265683 TI - White upconversion luminescence in CaF2:Yb(3+)/Eu(3+) powders via the incorporation of Y(3+) ions. AB - White upconversion luminescence (UCL) was achieved under 980 nm excitation in the CaF2:Yb(3+)/Eu(3+) material using Y(3+) to adjust the luminescence performance. In this luminescent system, Yb(3+) not only plays the role of a sensitizer of Eu(3+), but also generates green fluorescence from Yb(3+) dimers (2-Yb(3+)) by cooperative transitions in the CaF2 matrix. One of the primary colors of green corresponds to the 2-Yb(3+) cooperative emission exactly. Eu(3+) acts as an activator for emitting red and blue fluorescence simultaneously. Interestingly, the color of the UCL can be controlled by adjusting the doping concentration of Y(3+) ions, and white UCL was realized when the concentration of Y(3+) was 1%. PMID- 27265682 TI - Adaptation of muscle activity in scapular dyskinesis test for collegiate baseball players. AB - BACKGROUND: The characteristics of scapular muscle activities in elevation and descent exercises have yet to be elucidated to assess scapular dyskinesis. The purpose of this study was to identify the adaptation of electromyograph (EMG) activities of the upper trapezius (UT), lower trapezius (LT), serratus anterior (SA), and anterior deltoid (AD) muscles with different weight loads in flexion (FLX) and abduction (ABD) in collegiate baseball players. MATERIALS AND METHODS: Twenty eight individuals, including 13 pitchers, were tested. Normalized EMG signals for the UT, LT, SA, AD muscle of the both the dominant (DOM) and nondominant (NON) side were blocked at every 1 second during each of the exercises. A 3-way repeated analysis of variance design was used to identify differences in the mean values between DOM and NON and between FLX and ABD for DOM. RESULTS: The mean EMG value of the UT in the DOM was significantly less than that of the NON for all joint angles (P < .01), whereas the mean EMG value of the LT in the DOM was significantly greater than that of the NON (P < .01). In contrast, no difference in the SA EMG activity was determined between DOM and NON. However, the mean EMG value of SA in FLX was significantly greater than in ABD (P < .01). CONCLUSION: This study identified an apparent adaptation of scapular muscle activities in the currently advocated scapular dyskinesis test for healthy active overhead athletes who are vulnerable to shoulder pathologies. PMID- 27265684 TI - A Plasmodium-like virulence effector of the soybean cyst nematode suppresses plant innate immunity. AB - Heterodera glycines, the soybean cyst nematode, delivers effector proteins into soybean roots to initiate and maintain an obligate parasitic relationship. HgGLAND18 encodes a candidate H. glycines effector and is expressed throughout the infection process. We used a combination of molecular, genetic, bioinformatic and phylogenetic analyses to determine the role of HgGLAND18 during H. glycines infection. HgGLAND18 is necessary for pathogenicity in compatible interactions with soybean. The encoded effector strongly suppresses both basal and hypersensitive cell death innate immune responses, and immunosuppression requires the presence and coordination between multiple protein domains. The N-terminal domain in HgGLAND18 contains unique sequence similarity to domains of an immunosuppressive effector of Plasmodium spp., the malaria parasites. The Plasmodium effector domains functionally complement the loss of the N-terminal domain from HgGLAND18. In-depth sequence searches and phylogenetic analyses demonstrate convergent evolution between effectors from divergent parasites of plants and animals as the cause of sequence and functional similarity. PMID- 27265685 TI - 2-Aryl-8-aza-3-deazaadenosine analogues of 5'-O-[N-(salicyl)sulfamoyl]adenosine: Nucleoside antibiotics that block siderophore biosynthesis in Mycobacterium tuberculosis. AB - A series of 5'-O-[N-(salicyl)sulfamoyl]-2-aryl-8-aza-3-deazaadenosines were designed to block mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) through inhibition of the essential adenylating enzyme MbtA. The synthesis of the 2-aryl-8-aza-3-deazaadenosine nucleosides featured sequential copper-free palladium-catalyzed Sonogashira coupling of a precursor 4-cyano-5-iodo-1,2,3 triazolonucleoside with terminal alkynes and a Minakawa-Matsuda annulation reaction. These modified nucleosides were shown to inhibit MbtA with apparent Ki values ranging from 6.1 to 25nM and to inhibit Mtb growth under iron-deficient conditions with minimum inhibitory concentrations ranging from 12.5 to >50MUM. PMID- 27265686 TI - Thiazolo[3,2-a]benzimidazol-3(2H)-one derivatives: Structure-activity relationships of selective nucleotide pyrophosphatase/phosphodiesterase1 (NPP1) inhibitors. AB - Ecto-nucleotide pyrophosphatase/phosphodiesterase1 (NPP1) is the most important member of the NPP family, which consists of seven closely related proteins (NPP1 NPP7). This glycoprotein is a membrane-associated or secreted enzyme, which catalyzes the hydrolysis of a wide range of phosphodiester bonds, e.g., in nucleoside triphosphates, dinucleotides and nucleotide sugars. NPP1 plays a crucial role in various physiological functions including bone mineralization, soft-tissue calcification, and insulin receptor signaling. Recently, an upregulated expression of NPP1 has been observed in astrocytic brain cancers. Therefore, NPP1 has been proposed as a novel drug target for the treatment of glioblastoma. Despite their therapeutic potential, only few NPP1 inhibitors have been reported to date, which are in most cases non- or only moderately selective. The best investigated NPP1 inhibitors so far are nucleotide derivatives and analogs, however they are not orally bioavailable due to their high polarity. We identified thiazolo[3,2-a]benzimidazol-3(2H)-one derivatives as a new class of NPP1 inhibitors with drug-like properties. Among the 25 derivatives investigated in the present study, 2-[(5-iodo-2-furanyl)methylene]thiazolo[3,2-a]benzimidazol 3(2H)-one (17) was found to be the most potent NPP1 inhibitor with a Ki value of 467nM versus ATP as a substrate and an un-competitive mechanism of inhibition. Compound 17 did not inhibit other human ecto-nucleotidases, including NTPDase1 (CD39), NTPDases2-3, NPP2, NPP3, tissue-nonspecific alkaline phosphatase (TNAP), and ecto-5'-nucleotidase (eN, CD73), and is thus highly selective for NPP1. PMID- 27265688 TI - Child maltreatment, attachment and psychopathology: mediating relations. PMID- 27265687 TI - A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin. AB - The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I1-type imidazoline receptors (I1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from alpha2-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine-derived compounds with anticancer potential and devoid of alpha2-adrenoceptor effects by means of ligand- and structure-based drug design approaches. Starting from a large virtual library, eleven compounds were selected, synthesized and submitted to biological evaluation. The most active compound 5 exhibited a cytotoxic profile similar to that of rilmenidine, but without appreciable affinity to alpha2-adrenoceptors. In addition, compound 5 significantly enhanced the apoptotic response to doxorubicin, and may thus represent an important tool for the development of better adjuvant chemotherapeutic strategies for doxorubicin-insensitive cancers. PMID- 27265689 TI - Shorter hospitalizations at the expense of quality? Experiences of inpatient psychiatry in the post-institutional era. PMID- 27265691 TI - Understanding the burnout experience: recent research and its implications for psychiatry. AB - The experience of burnout has been the focus of much research during the past few decades. Measures have been developed, as have various theoretical models, and research studies from many countries have contributed to a better understanding of the causes and consequences of this occupationally-specific dysphoria. The majority of this work has focused on human service occupations, and particularly health care. Research on the burnout experience for psychiatrists mirrors much of the broader literature, in terms of both sources and outcomes of burnout. But it has also identified some of the unique stressors that mental health professionals face when they are dealing with especially difficult or violent clients. Current issues of particular relevance for psychiatry include the links between burnout and mental illness, the attempts to redefine burnout as simply exhaustion, and the relative dearth of evaluative research on potential interventions to treat and/or prevent burnout. Given that the treatment goal for burnout is usually to enable people to return to their job, and to be successful in their work, psychiatry could make an important contribution by identifying the treatment strategies that would be most effective in achieving that goal. PMID- 27265692 TI - Draft diagnostic guidelines for ICD-11 mental and behavioural disorders available for review and comment. PMID- 27265690 TI - Childhood adversities and psychosis: evidence, challenges, implications. AB - There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities - particularly exposure to multiple adversities involving hostility and threat - do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID- 27265693 TI - Can separation anxiety disorder escape its attachment to childhood? PMID- 27265694 TI - The many faces of narcissism. PMID- 27265695 TI - Time for a global commission on mental health institutions. PMID- 27265697 TI - Whether "psychosis" is best conceptualized as a continuum or in categories is an empirical, practical and political question. PMID- 27265696 TI - Psychosis as a transdiagnostic and extended phenotype in the general population. AB - A large body of research indicates that weak expressions of positive psychotic symptoms ("psychotic experiences") can be measured in the general population, and likely represent the behavioural manifestation of distributed multifactorial (genetic and non-genetic) risk for psychosis. Psychotic experiences are a transdiagnostic phenomenon: the majority of individuals with these experiences have a diagnosis of non-psychotic disorder, particularly common mental disorder, in which psychotic experiences predict greater illness severity and poorer treatment response. Some of the people with common mental disorder and psychotic experiences will present to mental health services meeting criteria for "clinical high risk". Treatment of the transdiagnostic dimension of psychosis in individuals with common mental disorder who meet "clinical high risk" criteria thus may improve outcome (which cannot be interpreted as prevention of "schizophrenia"). Subthreshold psychotic experiences are transitory in about 80% of individuals, while around 20% go on to develop persistent psychotic experiences and 7% a psychotic disorder, with an annual transition rate of 0.5 1%. Persistence is associated, on the one hand, with environmental exposures, particularly childhood trauma, and, on the other, with network-type dynamic interactions between psychotic experiences themselves (e.g., interactions between hallucinatory experiences and delusional ideation) and between symptom dimensions (e.g., interactions between affective symptoms and psychotic experiences, or interactions between subthreshold negative symptoms and psychotic experiences). The study of psychotic experiences is helping to elucidate the mechanisms by which environmental and genetic influences shape the transdiagnostic expression of psychosis proneness, that is mostly transitory but may first become persistent over time and eventually give rise to transition to a psychotic disorder. PMID- 27265698 TI - Epistemological error and the illusion of phenomenological continuity. PMID- 27265699 TI - Causal narratives and psychotic phenomena. PMID- 27265700 TI - Psychosis as a continuous phenotype in the general population: the thin line between normality and pathology. PMID- 27265701 TI - Psychotic experiences and their significance. PMID- 27265702 TI - High time for a paradigm shift in psychiatry. PMID- 27265703 TI - Conceptualizing psychotic disorders: don't throw the baby out with the bathwater. PMID- 27265704 TI - Population-based analysis of health care contacts among suicide decedents: identifying opportunities for more targeted suicide prevention strategies. AB - The objective of this study was to detail the nature and correlates of mental health and non-mental health care contacts prior to suicide death. We conducted a systematic extraction of data from records at the Office of the Chief Coroner of Ontario of each person who died by suicide in the city of Toronto from 1998 to 2011. Data on 2,835 suicide deaths were linked with provincial health administrative data to identify health care contacts during the 12 months prior to suicide. Sub-populations of suicide decedents based on the presence and type of mental health care contact were described and compared across socio demographic, clinical and suicide-specific variables. Time periods from last mental health contact to date of death were calculated and a Cox proportional hazards model examined covariates. Among suicide decedents, 91.7% had some type of past-year health care contact prior to death, 66.4% had a mental health care contact, and 25.3% had only non-mental health contacts. The most common type of mental health contact was an outpatient primary care visit (54.0%), followed by an outpatient psychiatric visit (39.8%), an emergency department visit (31.1%), and a psychiatric hospitalization (21.0%). The median time from last mental health contact to death was 18 days (interquartile range 5-63). Mental health contact was significantly associated with female gender, age 25-64, absence of a psychosocial stressor, diagnosis of schizophrenia or bipolar disorder, past suicide attempt, self-poisoning method and absence of a suicide note. Significant differences between sub-populations of suicide decedents based on the presence and nature of their health care contacts suggest the need for targeting of community and clinical-based suicide prevention strategies. The predominance of ambulatory mental health care contacts, often close to the time of death, reinforce the importance of concentrating efforts on embedding risk assessment and care pathways into all routine primary and specialty clinical care, and not only acute care settings. PMID- 27265705 TI - Does menopausal transition really influence mental health? Findings from the prospective long-term Zurich study. AB - In the prospective long-term Zurich study, we re-examined the hypothesized association between mental health problems in women and the transition through menopausal stages. One hundred sixty-eight women from a population-based Swiss community cohort were prospectively followed up from age 21 to 50. At age 50, the occurrence of hot flushes/night sweats and sleep disturbances was significantly more frequent in peri- and post-menopausal women. Irritability/nervousness was increased only in peri-menopausal women, but that association was accounted for by neuroticism trait scores at age 30. Transitions to peri- or post-menopause were not related to changes in either the prevalence rates of DSM major depressive episode or anxiety disorders, or the course of psychopathological syndromes as assessed by the Symptom Checklist 90 - Revised. The null associations held when adjusting for duration of reproductive period or age at menopause. Preceding mental health problems between ages 21 and 41, increased neuroticism trait scores at age 30, and concurrent psychosocial distress were significantly related to mental health problems occurring between ages 41 and 50. Depending upon the cut-off point that was chosen, the arbitrary dichotomization of a continuous depression outcome produced spurious associations with the menopausal transition. We conclude that mental health problems between ages 41 and 50 are probably not directly related to the menopausal transition, and that previously reported associations could be false positives due to inadequate dichotomizations, reporting bias, undisclosed multiple adjustments or overfitting. PMID- 27265706 TI - The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity. AB - Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. CHANGE was a randomized, parallel-group, superiority, multi-centre trial with blinded outcome assessment, testing the efficacy of an intervention aimed to improve cardiovascular risk profile and hereby potentially reduce mortality. A total of 428 patients with schizophrenia spectrum disorders and abdominal obesity were recruited and centrally randomized 1:1:1 to 12 months of lifestyle coaching plus care coordination plus treatment as usual (N=138), or care coordination plus treatment as usual (N=142), or treatment as usual alone (N=148). The primary outcome was 10-year risk of cardiovascular disease assessed post-treatment and standardized to age 60. At follow-up, the mean 10-year risk of cardiovascular disease was 8.4 +/- 6.7% in the group receiving lifestyle coaching, 8.5 +/- 7.5% in the care coordination group, and 8.0 +/- 6.5% in the treatment as usual group (p=0.41). We found no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, physical activity, weight, diet and smoking. In conclusion, the CHANGE trial did not support superiority of individual lifestyle coaching or care coordination compared to treatment as usual in reducing cardiovascular risk in patients with schizophrenia spectrum disorders and abdominal obesity. PMID- 27265708 TI - Smoking cessation should be an integral part of serious mental illness treatment. PMID- 27265709 TI - Physical activity and mental health: evidence is growing. PMID- 27265707 TI - Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis. AB - Type 2 diabetes mellitus (T2DM) is highly predictive of cardiovascular diseases and can have particularly deleterious health impacts in people with severe mental illness (SMI), i.e. schizophrenia, bipolar disorder or major depressive disorder. This meta-analysis aimed: a) to describe pooled frequencies of T2DM in people with SMI; b) to analyze the influence of demographic, illness and treatment variables as well as T2DM assessment methods; and c) to describe T2DM prevalence in studies directly comparing persons with each specific SMI diagnosis to general population samples. The trim and fill adjusted pooled T2DM prevalence among 438,245 people with SMI was 11.3% (95% CI: 10.0%-12.6%). In antipsychotic-naive participants, the prevalence of T2DM was 2.9% (95% CI: 1.7%-4.8%). There were no significant diagnostic subgroup differences. A comparative meta-analysis established that multi-episode persons with SMI (N=133,470) were significantly more likely to have T2DM than matched controls (N=5,622,664): relative risk, RR=1.85, 95% CI: 1.45-2.37, p<0.001. The T2DM prevalence was consistently elevated in each of the three major diagnostic subgroups compared to matched controls. Higher T2DM prevalences were observed in women with SMI compared to men (RR=1.43, 95% CI: 1.20-1.69, p<0.001). Multi-episode (versus first-episode) status was the only significant predictor for T2DM in a multivariable meta regression analysis (r(2) =0.52, p<0.001). The T2DM prevalence was higher in patients prescribed antipsychotics, except for aripriprazole and amisulpride. Routine screening and multidisciplinary management of T2DM is needed. T2DM risks of individual antipsychotic medications should be considered when making treatment choices. PMID- 27265710 TI - Is neuroimaging clinically useful in subjects at high risk for psychosis? PMID- 27265711 TI - Identifying multimodal signatures associated with symptom clusters: the example of the IMAGEMEND project. PMID- 27265712 TI - The 30-year mental health legacy of the Chernobyl disaster. PMID- 27265713 TI - Problem Management Plus (PM+): pilot trial of a WHO transdiagnostic psychological intervention in conflict-affected Pakistan. PMID- 27265714 TI - Treating post-traumatic stress disorder by resource activation in Cambodia. PMID- 27265715 TI - High burden of subthreshold DSM-5 post-traumatic stress disorder in U.S. military veterans. PMID- 27265716 TI - Big Data in mental health: a challenging fragmented future. PMID- 27265717 TI - Specific anxiety disorders and subsequent risk for bipolar disorder: a nationwide study. PMID- 27265718 TI - Tracing Emil Kraepelin in the Nobel Prize archive. PMID- 27265719 TI - Improving the mental health of women and girls: psychiatrists as partners for change. PMID- 27265720 TI - WPA Scientific Sections: update on the activities. PMID- 27265721 TI - Triazolopyrimidines as a New Herbicidal Lead for Combating Weed Resistance Associated with Acetohydroxyacid Synthase Mutation. AB - Acetohydroxyacid synthase (AHAS; also known as acetolactate synthase; EC 2.2.1.6, formerly EC 4.1.3.18) is the first common enzyme in the biosynthetic pathway leading to the branched-chain amino acids in plants and a wide range of microorganisms. Weed resistance to AHAS-inhibiting herbicides, increasing at an exponential rate, is becoming a global problem and leading to an urgent demand of developing novel compounds against both resistant and wild AHAS. In the present work, a series of novel 2-aroxyl-1,2,4-triazolopyrimidine derivatives (a total of 55) were designed and synthesized with the aim to discover an antiresistant lead compound. Fortunately, the screening results indicated that many of the newly synthesized compounds showed a better, even excellent, inhibition effect against both the wild-type Arabidopsis thaliana AHAS and P197L mutants. Among them, compounds 5-3 to 5-17, compounds 5-19 to 5-26, compounds 5-28 to 5-45, and compound 5-48 have the lower values of resistance factor (RF) and display a potential power to overcome resistance associated with the P197L mutation in the enzyme levels. Further greenhouse in vivo assay showed that compounds 5-15 and 5 20 displayed "moderate" to "good" herbicidal activity against both the wild type and the resistant (P197L mutation) Descurainia sophia, even at a rate as low as 0.9375 (g of ai/ha). The above results indicated that these two compounds could be used as new leads for the future development of antiresistance herbicides. PMID- 27265722 TI - Tinnitus is associated with reduced sound level tolerance in adolescents with normal audiograms and otoacoustic emissions. AB - Recent neuroscience research suggests that tinnitus may reflect synaptic loss in the cochlea that does not express in the audiogram but leads to neural changes in auditory pathways that reduce sound level tolerance (SLT). Adolescents (N = 170) completed a questionnaire addressing their prior experience with tinnitus, potentially risky listening habits, and sensitivity to ordinary sounds, followed by psychoacoustic measurements in a sound booth. Among all adolescents 54.7% reported by questionnaire that they had previously experienced tinnitus, while 28.8% heard tinnitus in the booth. Psychoacoustic properties of tinnitus measured in the sound booth corresponded with those of chronic adult tinnitus sufferers. Neither hearing thresholds (<=15 dB HL to 16 kHz) nor otoacoustic emissions discriminated between adolescents reporting or not reporting tinnitus in the sound booth, but loudness discomfort levels (a psychoacoustic measure of SLT) did so, averaging 11.3 dB lower in adolescents experiencing tinnitus in the acoustic chamber. Although risky listening habits were near universal, the teenagers experiencing tinnitus and reduced SLT tended to be more protective of their hearing. Tinnitus and reduced SLT could be early indications of a vulnerability to hidden synaptic injury that is prevalent among adolescents and expressed following exposure to high level environmental sounds. PMID- 27265723 TI - Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation. AB - OBJECTIVES: Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100MUM may be supratherapeutic, levels of at least 30MUM may be needed to improve wound healing and levels may need to reach 70MUM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain >=30MUM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels <30MUM. This study focuses on the plasma Ox levels in HD patients. DESIGN AND METHODS: A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. RESULTS: Mean plasma Ox levels decreased 71% during the intradialytic period (22.3+/-11.1MUM to 6.4+/-3.2MUM, P<0.001). In regression analysis, pre-HD plasma AA levels <=100MUM were not associated with a pre-HD plasma Ox level>=30MUM, even if ferritin levels were increased. Pre-HD plasma Ox levels >=20 or >=30MUM were not associated with lower cumulative 4-year survival. CONCLUSIONS: Pre-HD plasma AA levels up to 100MUM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels. PMID- 27265724 TI - Ni-Catalyzed Amination Reactions: An Overview. AB - Nitrogen-containing organic compounds are valuable in many fields of science and industry. The most reliable method for the construction of C(sp(2) )-N bonds is undoubtedly palladium-catalyzed amination. In spite of the great achievements made in this area, the use of expensive Pd-based catalysts constitutes an important limitation for large-scale applications. Since nickel is the least expensive and most abundant among the group 10 metals, the interest in Ni-based catalysts for processes typically catalyzed by palladium has grown considerably over the last few years. Herein, we revise the development of Ni-catalyzed amination reactions, emphasizing the most relevant and recent advances in the field. PMID- 27265725 TI - Safety, tolerability, and seizure control during long-term treatment with adjunctive brivaracetam for partial-onset seizures. AB - OBJECTIVES: To report pooled safety/tolerability and seizure outcome data from adults with uncontrolled partial-onset (focal) seizures (POS) receiving adjunctive brivaracetam (BRV) during phase IIb/III and long-term follow-up (LTFU) studies. METHODS: Seizure outcome data were pooled from phase IIb (NCT00175929 and NCT00175825), III/IIIb (NCT00490035, NCT00464269, NCT00504881, and NCT01261325) and associated LTFU studies (NCT00175916, NCT00150800, and NCT01339559). Safety/tolerability data were pooled from these studies plus NCT01405508, NCT01653262, and NCT01728077 (LTFU). Patients received placebo (during core studies) or BRV 5-200 mg/day. Safety/tolerability and seizure outcomes (BRV modal doses 50-200 mg/day) were assessed until January 17, 2014. RESULTS: Of 2,186 patients (97.3% with POS and 2.7% with other seizure types) who received BRV 50-200 mg/day, 2,051 (93.8%) completed core studies and continued in LTFU studies. Total BRV exposure: 5,339.4 patient-years (>=8.0 years in 41 patients); 6-, 12-, 24-, and 60-month retention: 91.0%, 79.8%, 68.1%, and 54.4%, respectively. Safety/tolerability data pooled from 2,186 patients: >=1 treatment emergent adverse event (TEAE) reported by 1,848 (84.5%) patients; 1,184 (54.2%) reported >=1 TEAE considered treatment-related. Most frequent TEAEs (>=10%): headache (20.9%), dizziness (17.5%), somnolence (15.2%), nasopharyngitis (13.2%), fatigue (11.3%), and convulsion (10.6%). Serious TEAEs (SAEs) and treatment related SAEs: 401 (18.3%) and 95 (4.3%) patients, respectively. Of 28 (1.3%) deaths, four (14.3%) were considered possibly treatment related by the investigator. Pooled seizure outcome data (1,836 patients): median POS frequency/28 days at baseline was 8.9; on treatment, median percentage reduction from baseline in POS/28 days was 48.8%, and >=50% responder rate was 48.7%. Complete seizure freedom: 4.9%, 4.2%, 3.0%, and 3.3% for >=6, 12, 24, and 60 months, respectively. Improvements were seen in health-related quality of life (HRQoL) from baseline, assessed by Quality of Life in Epilepsy Inventory-31. SIGNIFICANCE: Adjunctive BRV treatment in adults with POS was effective and generally well tolerated when administered long-term (>=8.0 years). Retention was high and HRQoL improvements were observed. PMID- 27265726 TI - Magnetic hyperthermia efficiency and (1)H-NMR relaxation properties of iron oxide/paclitaxel-loaded PLGA nanoparticles. AB - Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar (1)H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe NPs in PLGA-NPs also made it possible to maintain Neel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15-20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe NPs designed for MFH applications. PMID- 27265727 TI - The MDM2-p53-pyruvate carboxylase signalling axis couples mitochondrial metabolism to glucose-stimulated insulin secretion in pancreatic beta-cells. AB - Mitochondrial metabolism is pivotal for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. However, little is known about the molecular machinery that controls the homeostasis of intermediary metabolites in mitochondria. Here we show that the activation of p53 in beta-cells, by genetic deletion or pharmacological inhibition of its negative regulator MDM2, impairs GSIS, leading to glucose intolerance in mice. Mechanistically, p53 activation represses the expression of the mitochondrial enzyme pyruvate carboxylase (PC), resulting in diminished production of the TCA cycle intermediates oxaloacetate and NADPH, and impaired oxygen consumption. The defective GSIS and mitochondrial metabolism in MDM2-null islets can be rescued by restoring PC expression. Under diabetogenic conditions, MDM2 and p53 are upregulated, whereas PC is reduced in mouse beta-cells. Pharmacological inhibition of p53 alleviates defective GSIS in diabetic islets by restoring PC expression. Thus, the MDM2-p53-PC signalling axis links mitochondrial metabolism to insulin secretion and glucose homeostasis, and could represent a therapeutic target in diabetes. PMID- 27265728 TI - Transcranial direct current stimulation produces long-lasting attenuation of cocaine-induced behavioral responses and gene regulation in corticostriatal circuits. AB - Transcranial direct current stimulation (tDCS) is a non-invasive method to modulate cortical excitability. This technique is a promising emerging tool to treat several neuropathologies, including addiction. We have previously shown in mice that repeated tDCS normalizes pathological behaviors associated with chronic nicotine exposure. Here, we evaluated, in adult female mice, the impact of tDCS on cocaine-induced behavior and gene regulation in corticostriatal circuits implicated in psychostimulant addiction. Anodal tDCS was applied transcranially over the frontal cortex. Three weeks after repeated tDCS, we investigated the induction of a gene expression marker (Zif268) by cocaine (25 mg/kg) in 26 cortical and 23 striatal regions using in situ hybridization histochemistry. We also assessed place preference conditioning by cocaine (5, 10 and 25 mg/kg). tDCS pretreatment increased basal expression and attenuated cocaine (25 mg/kg)-induced expression of Zif268 in specific corticostriatal circuits. Cocaine-induced locomotor activation (25 mg/kg) and place preference conditioning (5 and 25 mg/kg) were also reduced. These results demonstrate that tDCS can attenuate molecular and behavioral responses to cocaine for several weeks. Together, our findings provide pre-clinical evidence that such electrical brain stimulation may be useful to modify the psychostimulant addiction risk. PMID- 27265731 TI - Risk assessment of excessive CO2 emission on diatom heavy metal consumption. AB - Diatoms are the dominant group of phytoplankton in the modern ocean, accounting for approximately 40% of oceanic primary productivity and critical foundation of coastal food web. Rising dissolution of anthropogenic CO2 in seawater may directly/indirectly cause ocean acidification and desalination. However, little is known about dietary diatom-associated changes, especially for diatom heavy metal consumption sensitivity to these processes, which is important for seafood safety and nutrition assessment. Here we show some links between ocean acidification/desalination and heavy metal consumption by Thalassiosira weissflogii. Excitingly, under desalination stress, the relationships between Cu, Zn, and Cd were all positively correlated, especially between Cu and Zn (r=0.989, total intracellular concentration) and between Zn and Cd (r=0.962, single-cell intracellular concentration). Heavy metal consumption activity in decreasing order was acidificationchicken->chicken manure->soil->rice plant. AB - Roxarsone (ROX), a widely used feed additive, occurs as itself and its metabolites in animal manure. Rice is prone to accumulate As than other staple food. Four diets with 0, 40, 80 and 120mgROXkg(-1) were fed in chickens, and four chicken manures (CMs) were collected to fertilize rice plants in a soil culture experiment. Linear regression analysis shows that the slopes of As species including 4-hydroxy-phenylarsonic acid, As(V), As(III), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in CM versus dietary ROX were 0.033, 0.314, 0.033, 0.054 and 0.138, respectively. Both As(III) and DMA were determined in all rice grains, and As(III), As(V), MMA and DMA in rice hull, but detectable As forms in rice straws and soils increased with increasing ROX dose. Grain As(III) was unrelated to ROX dose but exceeded the Chinese rice As limit (0.15mgAs(III)kg(-1)). Dietary ROX enhanced straw As(III) mostly, with the slope of 0.020, followed by hull DMA (0.006) and grain DMA (0.002). The slopes of soil As(V) and As(III) were 0.003 and 0.001. This is the first report illustrating the quantitative delivery of ROX via food chain, which helps to evaluate health and environmental risks caused by ROX use in animal production. PMID- 27265739 TI - Distribution, sources and ecological risk assessment of polycyclic aromatic hydrocarbons in water and sediments from Tiber River and estuary, Italy. AB - The concentration, source and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in the Tiber River and its environmental impact on the Tyrrhenian Sea (Central Mediterranean Sea) were estimated. The 16 priority PAHs were determined in the water dissolved phase (DP), suspended particulate matter (SPM) and sediments collected from 21 sites in four different seasons. Total concentrations of PAHs ranged from 10.3 to 951.6ngL(-1) and from 36.2 to 545.6ngg(-1) in water (sum of DP and SPM) and in sediment samples, respectively. The compositions of PAHs showed that 2- to 4-ring PAHs were abundant in DP, 4- to 6-ring PAHs were predominant in SPM samples, and 4- to 5-ring PAHs were abundant in sediments. The diagnostic ratio analysis indicated that the PAHs mainly had a pyrolytic source. The toxic equivalent concentration of carcinogenic PAHs was 45.3ngTEQg(-1), suggesting low carcinogenic risk for Tiber River. Total PAHs loads into the sea were calculated in about 3161.7kgyear(-1) showing that this river is one of the main contribution sources of these contaminants to the Tyrrhenian Sea. PMID- 27265741 TI - Assessment of rice yield loss due to exposure to ozone pollution in Southern Vietnam. AB - The study domain covered the Eastern region of Southern of Vietnam that includes Ho Chi Minh City (HCMC) and five other provinces. Rice production in the domain accounted for 13% of the national total with three crop cycles per year. We assessed ozone (O3) induced rice production loss in the domain for 2010 using simulated hourly surface O3 concentrations (WRF/CAMx; 4km resolution). Simulated O3 was higher in January-February (largely overlaps the first crop) and September December (third crop), and lower in March-June (second crop). Spatially, O3 was higher in downwind locations of HCMC and were comparable with observed data. Relative yield loss (RYL) was assessed for each crop over the respective growing period (105days) using three metrics: AOT40, M7 and flux-based O3 dose of POD10. Higher RYL was estimated for the downwind of HCMC. Overall, the rice production loss due to O3 exposure in the study domain in 2010 was the highest for the first crop (up to 25,800metrictons), the second highest for the third crop (up to 21,500tons) and the least for the second crop (up to 6800tons). The low RYL obtained for the second crop by POD10 may be due to the use of a high threshold value (Y=10nmolm(-2)s(-1)). Linear regression between non-null radiation POD0 and POD10 had similar slopes for the first and third crop when POD0 was higher and very low slope for the second crop when POD0 was low. The results of this study can be used for the rice crop planning to avoid the period of potential high RYL due to O3 exposure. PMID- 27265742 TI - Docetaxel Combined With Bavituximab in Previously Treated, Advanced Nonsquamous Non-Small-Cell Lung Cancer. AB - BACKGROUND: Bavituximab is a phosphatidylserine-targeting antibody with a selective tumor, vascular-directed immune response. In this phase II trial the efficacy and safety of bavituximab combined with docetaxel for previously treated, advanced nonsquamous non-small-cell lung cancer were evaluated. PATIENTS AND METHODS: Patients were randomized 1:1:1 to receive docetaxel 75 mg/m(2) every 21 days for up to 6 cycles combined with weekly, blinded infusions of placebo, bavituximab 1 mg/kg, or bavituximab 3 mg/kg until disease progression or unacceptable toxicity. The primary end point was overall response rate (ORR), with a predefined end point of 26% in the bavituximab arms. After study unblinding, vial-coding discrepancies were discovered in the placebo and bavituximab 1 mg/kg groups. In exploratory analyses, data from these groups were pooled to form the control group and compared with the 3 mg/kg group. RESULTS: Efficacy end points in the bavituximab 3 mg/kg group (n = 41) and in the placebo/bavituximab 1 mg/kg group (n = 80), respectively, were as follows: ORR, 17.1% (95% confidence interval [CI], 5.6%-28.6%) and ORR, 11.3% (95% CI, 4.3% 18.2%); median progression-free survival 4.5 and 3.3 months (hazard ratio [HR], 0.74 [95% CI, 0.45-1.21]; P = .24); median overall survival 11.7 and 7.3 months (HR, 0.66 [95% CI, 0.40-1.10]; P = .11). Toxicities were manageable and similar between arms. CONCLUSION: The combination of bavituximab and docetaxel is well tolerated. Although no firm efficacy conclusions can be drawn and the trial did not meet the predefined primary end point, exploratory analyses suggest trends favoring the combination of bavituximab 3 mg/kg with docetaxel. This regimen is being evaluated in the ongoing, global, phase III SUNRISE trial. PMID- 27265743 TI - A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study. AB - Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (>=25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing. PMID- 27265744 TI - NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls. AB - Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimer's disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 * 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia. PMID- 27265745 TI - Erratum to "Down-regulation of hTERT and Cyclin D1 transcription via PI3K/Akt and TGF-beta pathways in MCF-7 cancer cells with PX-866 and Raloxifene" [Exp. Cell Res. 344 (2016) 95-102]. PMID- 27265746 TI - Suicide, Socio-economic Inequalities, Gender, and Psychiatric DisordersCommentary: Educational Levels and Risk of Suicide in Japan: The Japan Public Health Center Study (JPHC) Cohort I. PMID- 27265748 TI - An RNA Aptamer Inhibits a Mutation-Induced Inactivating Misfolding of a Serpin. AB - Most serpins are fast and specific inhibitors of extracellular serine proteases controlling biological processes such as blood coagulation, fibrinolysis, tissue remodeling, and inflammation. The inhibitory activity of serpins is based on a conserved metastable structure and their conversion to a more stable state during reaction with the target protease. However, the metastable state also makes serpins vulnerable to mutations, resulting in disease caused by inactive and misfolded monomeric or polymeric forms ("serpinopathy"). Misfolding can occur either intracellularly (type-I serpinopathies) or extracellularly (type-II serpinopathies). We have isolated a 2'-fluoropyrimidine-modified RNA aptamer, which inhibits a mutation-induced inactivating misfolding of the serpin alpha1 antichymotrypsin. It is the first agent able to stabilize a type-II mutation of a serpin without interfering with the inhibitory mechanism, thereby presenting a solution for the long-standing challenge of preventing pathogenic misfolding without compromising the inhibitory function. PMID- 27265747 TI - Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV Neu Model of HER2(+) Breast Cancer. AB - Many tumors are dependent on de novo fatty acid synthesis to maintain cell growth. Fatty acid synthase (FASN) catalyzes the final synthetic step of this pathway, and its upregulation is correlated with tumor aggressiveness. The consequences and adaptive responses of acute or chronic inhibition of essential enzymes such as FASN are not fully understood. Herein we identify Fasnall, a thiophenopyrimidine selectively targeting FASN through its co-factor binding sites. Global lipidomics studies with Fasnall showed profound changes in cellular lipid profiles, sharply increasing ceramides, diacylglycerols, and unsaturated fatty acids as well as increasing exogenous palmitate uptake that is deviated more into neutral lipid formation rather than phospholipids. We also showed that the increase in ceramide levels contributes to some extent in the mediation of apoptosis. Consistent with this mechanism of action, Fasnall showed potent anti tumor activity in the MMTV-Neu model of HER2(+) breast cancer, particularly when combined with carboplatin. PMID- 27265749 TI - Foamy Monocytes Are Enriched in cis-7-Hexadecenoic Fatty Acid (16:1n-9), a Possible Biomarker for Early Detection of Cardiovascular Disease. AB - Human monocytes respond to arachidonic acid, a secretory product of endothelial cells, by activating the de novo pathway of fatty acid biosynthesis, resulting in the acquisition of a foamy phenotype due to accumulation of cytoplasmic lipid droplets. Recruitment of foamy monocytes to endothelium is a key step in the formation of atherosclerotic plaques. Here we describe that lipid droplets of foamy monocytes are enriched in a rather uncommon fatty acid, cis-7-hexadecenoic acid (16:1n-9), a positional isomer of palmitoleic acid. 16:1n-9 was found to possess an anti-inflammatory activity both in vitro and in vivo that is comparable with that of omega-3 fatty acids and clearly distinguishable from the effects of palmitoleic acid. Selective accumulation in neutral lipids of phagocytic cells of an uncommon fatty acid reveals an early phenotypic change that may provide a biomarker of proatherogenicity, and a potential target for intervention in the early stages of cardiovascular disease. PMID- 27265750 TI - A combined variation of Palmaris longus and Flexor digitorum superficialis: Case report and review of literature. AB - The muscles of the anterior compartment of the forearm often exhibit anatomic variations. During dissection of the upper right limb of a preserved cadaver, morphological variations in the Palmaris longus and Flexor digitorum superficialis muscles were found. The Palmaris longus muscular fibers converged to a tendon that passed beneath the Flexor retinaculum, and inserted at the base of the middle phalanx of the fourth digit, replacing the tendon of Flexor digitorum superficialis. The Flexor digitorum superficialis was divided into two muscular heads: a digastric medial head giving tendons to the second and fifth digits, and a lateral head giving one tendon to the third digit. All these tendons were inserted in the respective digits by two bundles between which were located the tendon of the Flexor digitorum profundus muscle. Variations of flexor muscles must be documented because of their clinical significance and their potential use of these muscles in orthopaedic and reconstructive surgery. PMID- 27265751 TI - LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation. AB - Although mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinson's disease, their function is largely unknown. LRRK2 is pleiotropic in nature, shown to be involved in neurodegeneration and in more peripheral processes, including kidney functions, in rats and mice. Recent studies in zebrafish have shown conflicting evidence that removal of the LRRK2 WD40 domain may or may not affect dopaminergic neurons and/or locomotion. This study shows that ~50% LRRK2 knockdown in zebrafish causes not only neuronal loss but also developmental perturbations such as axis curvature defects, ocular abnormalities, and edema in the eyes, lens, and otic vesicles. We further show that LRRK2 knockdown results in significant neuronal loss, including a reduction of dopaminergic neurons. Immunofluorescence demonstrates that endogenous LRRK2 is expressed in the lens, brain, heart, spinal cord, and kidney (pronephros), which mirror the LRRK2 morphant phenotypes observed. LRRK2 knockdown results further in the concomitant upregulation of beta-synuclein, PARK13, and SOD1 and causes beta synuclein aggregation in the diencephalon, midbrain, hindbrain, and postoptic commissure. LRRK2 knockdown causes mislocalization of the Na(+) /K(+) ATPase protein in the pronephric ducts, suggesting that the edema might be linked to renal malfunction and that LRRK2 might be associated with pronephric duct epithelial cell differentiation. Combined, our study shows that LRRK2 has multifaceted roles in zebrafish and that zebrafish represent a complementary model to further our understanding of this central protein. (c) 2016 Wiley Periodicals, Inc. PMID- 27265752 TI - Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays. AB - INTRODUCTION: The purpose of this study is to compare the effect of increasing concentrations of direct anti-Xa oral anticoagulants (DOAC) apixaban-, edoxaban-, and rivaroxaban-enriched plasma samples on various prothrombin time (PT), activated partial thromboplastin time (APTT), heparin calibrated anti-Xa methods, and other coagulation assays. METHODS: Apixaban, edoxaban, or rivaroxaban was dissolved in dimethylsulfoxide and added to pooled normal plasma to obtain concentrations ranging from 0 ng/mL to approximately 600 ng/mL. The samples were tested using Innovin((r)) , Neoplastine((r)) CI Plus, Recombiplastin 2G, and Thromborel((r)) S for PT testing and Actin, Actin((r)) FS, Actin((r)) FSL, APTT Automate, and SynthaSIL for APTT. Samples were also tested using four different anti-Xa methods calibrated for unfractionated heparin or low molecular weight heparin. Special coagulation assays included antithrombin activity, lupus anticoagulant assays, and others. For special coagulation assays, the concentration of DOAC that resulted in a >15% change from baseline value was determined. DOAC quantification was performed using liquid chromatography-tandem mass spectrometry. RESULTS: All PT and APTT reagents demonstrated a higher sensitivity for edoxaban and rivaroxaban than for apixaban. Anti-Xa methods were able to detect low concentrations of DOAC. DOACs effected special coagulation assays to differing degrees, with lupus anticoagulant testing using dilute viper venom, the most sensitive test to the presence of anti-Xa DOAC. CONCLUSION: No PT or APTT reagent system effectively detected apixaban. All anti-Xa methods demonstrated sensitivity to low concentrations of DOAC. Dilute viper venom methods are exquisitely sensitive to anti-Xa DOAC, suggesting potential use of this assay for screening or measuring these drugs. PMID- 27265753 TI - Intracemetery biological variation at the fort ancient sunwatch village. AB - OBJECTIVES: We investigate intracemetery biological variation at the Fort Ancient SunWatch village (800-500 BP.) to test the hypothesis that the SunWatch population consisted of spatially structured biologically differentiated kin groups consisting of distinct local Late Woodland and non-local Mississippian biological populations. MATERIAL AND METHODS: The SunWatch sample contains 166 individuals: 63 adults and 103 subadults. We analyze intracemetery biological variation using two feature sets: the buccolingual diameters of the polar teeth in the permanent (n = 37) and deciduous (n = 26) dentitions. We apply matrix correlation models to biodistance and grave distance matrices in both data sets, evaluate burial outliers and individuals exhibiting a rare dental feature with interindividual biological distances, and evaluate potential cultural subgroups with Mahalanobis' distance. RESULTS: Matrix correlation analyses for both feature sets as well as interindividual and subgroup distances indicate the SunWatch village cemetery was kin structured, contained a single primary biological population, and also contained a small number of non-local individuals most of whom were from closely related populations. We thus reject the hypothesis that the SunWatch population consisted of biologically distinct Late Woodland and Mississippian biological populations. DISCUSSION: Although SunWatch village exhibited cultural attributes characteristic of both local Late Woodland and non local Mississippian groups, biologically the village was composed of one primary population. The lack of evidence for marked biological differentiation in the SunWatch village area at about 800-500 BP. suggests diffusion and acculturation may account for Mississippian cultural characteristics in southwestern Ohio Fort Ancient villages. If gene flow or migrations from biologically distinct Mississippian populations into southwestern Ohio occurred, either or both likely occurred well before 800 BP. This would have allowed the process of admixture time to produce a relatively homogeneous, nondifferentiated population. The latter alternative is consistent with the appearance in southwestern Ohio of non local individuals at one site linked to surrounding Mississippian regions at about 950 BP. Am J Phys Anthropol 160:719-728, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27265754 TI - Multiple sclerosis: The resolving lesion revealed. AB - A little studied lesion, the resolving lesion, is described in multiple sclerosis (MS). Unusual features of early resolving lesions comprised a fibrous astrogliotic parenchyma replete with lipid-laden (foamy) microglia/macrophages widely scattered throughout and lined up at the edge, separating demyelinated plaque from myelinated white matter. Ongoing myelin breakdown was absent, as was remyelination. Later resolving lesions displayed the unusual coexistence of macrophages and remyelination within the gliotic parenchyma. Collectively, these observations may provide for the first time evidence for a role in MS for mitigating factors like alternatively-activated (M2) microglia/macrophages, known to have an anti-inflammatory phenotype and to be associated with wound-healing and repair. PMID- 27265757 TI - Is There a Place for Apheresis in Patients with Severe Sepsis or Multi Organ Dysfunction Syndrome? AB - Severe sepsis and multiorgan dysfunction syndrome may develop in the course of severe sepsis, intoxication, poisoning, crush injury, asystole, drowning, and several other complications. When normal intensive care is insufficient despite vasoactive drugs, respiratory aid, and dialysis, the risk for death is extremely high. Only very little benefit has been noted in various trials using drug administration such as antibodies against TNF-alfa, immunoglobulin, pentoxifylline and high dose steroids. The use of apheresis (plasma exchange, plasmapheresis, adsorption) to remove toxins, cytokines, and other compounds has been tried in an unselective as well as selective manner. Data now exists that indicate increased survival by this type of therapy. It is time to focus on randomised controlled trials with these techniques to decide the efficacy of apheresis in this area. PMID- 27265755 TI - New Highly Oxygenated Germacranolides from Carpesium divaricatum and their Cytotoxic Activity. AB - Eight highly oxygenated germacranolides (1-8) including four new ones (2-5) were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by NMR experiment and HRESIMS data. The absolute configuration of 1 was established by circular dichroism (CD) method and X-ray diffraction, and the stereochemistry of the new compounds 2-5 were determined by similar CD spectra with 1. Compound 2 is the first hydroperoxyl germacrane from the genus Carpesium. The (13)C NMR data of 1, NMR data of 6-7, and their absolute configurations were reported for the first time. Two new compounds (2 and 4) and two known compounds (6 and 8) exhibited potent cytotoxicity against human cervical cancer (HeLa) cells, superior to that of the positive control doxorubicin. PMID- 27265758 TI - Multilineage Immune-Mediated Cytopenias in Childhood: A Report of Five Patients. AB - This study was performed to determine whether there is any distinction to be made between single and multiple-lineage cytopenias particularly with regard to natural history and prognosis. From December 1989 to May 1994, five of 50 children (median age 7 years) with chronic immune cytopenias were diagnosed with multi-lineage immune- ediated cytopenias. Two patients presented with immune thrombocytopenia (ITP) and later developed autoimmune hemolytic anemia (AIHA); one had ITP and immune eutropenia who subsequently became Coombs' positive but never developed AIHA. One child presented with ITP and immune neutropenia and later developed AIHA. The fifth child presented simultaneously with thrombocytopenia and neutropenia with positive antineutrophil antibody but without antiplatelet antibody and Coombs' positivity. Four patients were given primary therapy with IVIG and one with prednisone. One patient responded to prednisone but relapsed subsequently. Further treatment with IVIG roduced initial normalization of his counts with occasional fluctuation of the absolute neutrophil count. Two responded to IVIG and are in complete remission (CR). Of the two nonresponders to IVIG, one responded subsequently to prednisone and is in CR. The other one, after being refractory to multimodality treatment, was diagnosed with a lupus erythematosis variant and is currently on alternate day prednisone. Moderate thrombocytopenia and absolute neutropenia still persist. Multi-lineage immune-mediated cytopenias may represent a pathogenic phenomenon that is distinct from autoimmune single-lineage disease. Clinical response to treatment may correlate with these differences that may be genetic in origin. Clinical course and response to therapy are less predictable when autoimmune disease is present. PMID- 27265759 TI - The Levels of Sera Malondialdehyde, Erythrocyte Membrane Na+-K+/Mg++ and Ca++/Mg++ Adenosine 5' Triphosphatase in Patients with Sickle Cell Anemia. AB - The various membrane abnormalities of sickle erythrocytes may result from excessive accumulation of oxidant damage. We measured the sera levels of malondialdehyde, products of lipid peroxidation, Na+-K+/Mg++ Adenosine 5' triphosphatase (ATPase) and Ca++/Mg++ Adenosine 5' triphosphatase, erythrocyte membrane enzymes, in patients with sickle cell anemia and compared their levels with that of normal controls. MDA, Na+-K+/Mg++ and Ca++/Mg++ ATPase levels of control groups were 0.90 +/- 0.04 nmol/mL, 168 +/- 12.9 and 140.6 +/- 8.2 nmol Pi/mg prot/hour, respectively. MDA, Na+-K+/Mg++ and Ca++/Mg++ATPase levels of patients were 2.02 +/- 0.01 nmol/mL, 127.0 +/- 8.4 and 110.0 +/- 9.6 nmol Pi/mg prot/hour, respectively. Our experimental results showed that there was a significant increase in MDA levels of patients with sickle cell anemia as compared with that of the controls. However, erythrocyte membrane Na+-K+/Mg++ and Ca++/Mg++ ATPase levels of patients with sickle cell anemia were significantly lower than the, Na+-K+/Mg++ and Ca++/Mg++ ATPase levels of normal controls. PMID- 27265756 TI - Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC-39). AB - AIM: To investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes. MATERIALS AND METHODS: We conducted a retrospective observational cohort study, in a primary care setting in the Netherlands. Patients aged >=18 years with type 2 diabetes who were included in the ZODIAC cohort between 1998 and 2012 and who received metformin monotherapy at inclusion (n = 29 195), and had used metformin as monotherapy for at least 1 year before receiving dual therapy through the addition of an SU for at least 1 year were eligible for inclusion. The primary outcome was within-drug yearly change in body weight after receiving add-on therapy with individual SUs during 5 years of follow-up. The secondary outcome was within-drug yearly change in glycated haemoglobin (HbA1c). Annual changes in weight and HbA1c were estimated with linear mixed models, adjusted for age, gender and diabetes duration. RESULTS: A total of 2958 patients were included. No significant weight changes were observed within and between any of the individual SUs after treatment intensification (p = 0.24). In addition, no significant difference in weight between the add-on therapy combinations was observed (p = 0.26). The average HbA1c the year before intensification was 7.2% (55 mmol/mol) and dropped below 7.0% (53 mmol/mol) the year after. CONCLUSIONS: In patients with type 2 diabetes treated in primary care, strict glycaemic control can be maintained with SUs used as add-on therapy to metformin, without the offset of relevant weight changes. PMID- 27265761 TI - Isolated Acquired FX Deficiency: A Case Report. AB - A female with no previous history of bleeding presented with active bleeding from multiple body sites, declining hemoglolobin levels, and markedly prolonged prothrombin times (PT), and activated partial thromboplastin times (APTT) with incomplete correction on PT mix assays. This patient showed a severe deficiency of factor X. FX levels and bleeding were refractory to multiple transfusions of fresh frozen plasma. Although plasmapheresis was started with concomitant intravenous immunoglobulin and steroid therapy, the patient died. PMID- 27265760 TI - Two Rare Hemoglobin Variants in the Turkish Population (Hb G-Coushatta (B 22(B4) GLU-ALA and Hb J Iran (B 77 (EF1) HIS-ASP). PMID- 27265762 TI - Normal Pressure Hydrocephalus Associated with Chronic Alpha Interferon Treatment: A Case Report. AB - Chronic a-interferon use has been reported to cause a variety of neurotoxic side effects. This case summary suggests the possibility of a new neurotoxic side effect of normal pressure hydrocephalus following chronic a-interferon use. PMID- 27265763 TI - Inflammatory Pseudotumor of the Lung Associated with Anemia: A Case Report and Review of the Literature. AB - Inflammatory pseudotumor of the lung is a benign tumor which is rarely seen. A mass in the left lung was observed in the chest roentgenogram of an 8 year-old boy while investigating for anemia. Preoperative investigations could not render the exact diagnosis. Pneumonectomy was required in exploratris thoracotomy. Histopathologic diagnosis was fibrohistiocytic type of inflammatory pseudotumor. Four months after the operation, anemia was cured without any further treatment. PMID- 27265764 TI - In Reply. PMID- 27265765 TI - Concerns for Collagenase. PMID- 27265766 TI - Ugly aesthetic perception associated with emotional changes in experience of art by behavioural variant of frontotemporal dementia patients. AB - The aesthetic experience through art is a window into the study of emotions. Patients with behavioural variant of frontotemporal dementia (bvFTD) have early alteration of emotional processing. A new appreciation of art has been reported in some of these patients. We designed a computerized task using 32 abstract paintings that allowed us to investigate the integrity of patients' emotions when viewing the artwork. We evaluated both conscious and explicit appraisal of emotions [aesthetic judgment (beautiful/ugly), emotional relevance (affected or not by the painting), emotional valence (pleasant/unpleasant), emotional reaction (adjective choice) and arousal] and unconscious processing. Fifteen bvFTD patients and 15 healthy controls were included. BvFTD patients reported that they were "little touched" by the paintings. Aesthetic judgment was very different between the two groups: the paintings were considered ugly (negative aesthetic bias) and unpleasant (negative emotional bias) more often by the patients than by controls. Valence and aesthetic judgments correlated in both groups. In addition, there was a positive bias in the implicit task and for explicit emotional responses. Patients frequently chose the word "sad" and rarely expressed themselves with such adjectives as "happy". Our results suggest that bvFTD patients can give an aesthetic judgment, but present abstraction difficulties, as spectators, resulting from impairments in the cognitive processes involved. They also have difficulties in terms of emotional processes with the loss of the ability to feel the emotion per se (i.e., to feel an emotion faced with art) linked to behaviour assessment. This cognitive approach allows us to better understand which spectators are bvFTD patients and to show interactions between emotions and behavioural disorders. PMID- 27265767 TI - Bacterial transcription: A tale of two specificities. PMID- 27265770 TI - Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target. AB - The consensus hypothesis on coronary atherosclerosis suggests high LDL-C levels as the major cause and pursues it as the therapeutic target, explicitly assuming: (i) tunica intima of human coronaries consists of only one cell layer - endothelium, situated on a thin layer of scarcely cellular matrix; and (ii) subendothelial lipoprotein retention initiates the disease. Facts showed: (i) normal tunica intima invariably consists of multiple cellular layers; and (ii) initial lipid depositions occurred in the deepest layers of tunica intima. This review suggests that coronary atherosclerosis starts with pathological intimal expansion, resulting in intimal hypoxia and neovascularization from adventitial vasa vasorum, facilitating lipoprotein extraction by previously avascular deep intimal tissues. Until the hypothesis incorporates real knowledge, our efforts will probably be off-target. PMID- 27265769 TI - Advancing microbial sciences by individual-based modelling. AB - Remarkable technological advances have revealed ever more properties and behaviours of individual microorganisms, but the novel data generated by these techniques have not yet been fully exploited. In this Opinion article, we explain how individual-based models (IBMs) can be constructed based on the findings of such techniques and how they help to explore competitive and cooperative microbial interactions. Furthermore, we describe how IBMs have provided insights into self-organized spatial patterns from biofilms to the oceans of the world, phage-CRISPR dynamics and other emergent phenomena. Finally, we discuss how combining individual-based observations with IBMs can advance our understanding at both the individual and population levels, leading to the new approach of microbial individual-based ecology (MUIBE). PMID- 27265771 TI - In vitro and ex vivo models of multiple sclerosis. AB - Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS). Current therapies suppress a misdirected myelin-destructive immune response. To combat the progressive, neurodestructive phase of MS, the therapeutic research focus is currently on compounds that might boost the endogenous potential of the brain to remyelinate axons, thereby achieving lesion repair. Here, we describe the testing of fingolimod on cultures of oligodendrocytes (OLs) and organotypic brain slices. We detail the protocols, pros, and cons of these in vitro and ex vivo approaches, along with the potential benefit of exploiting skin-punch biopsies from patients with MS, before concluding with a summary of future developments. PMID- 27265768 TI - Opportunistic intruders: how viruses orchestrate ER functions to infect cells. AB - Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus-ER interactions has become available, these insights may lead to the development of crucial therapeutic agents. PMID- 27265772 TI - Immune-competent human skin disease models. AB - All skin diseases have an underlying immune component. Owing to differences in animal and human immunology, the majority of drugs fail in the preclinical or clinical testing phases. Therefore animal alternative methods that incorporate human immunology into in vitro skin disease models are required to move the field forward. This review summarizes the progress, using examples from fibrosis, autoimmune diseases, psoriasis, cancer and contact allergy. The emphasis is on co cultures and 3D organotypic models. Our conclusion is that current models are inadequate and future developments with immune-competent skin-on-chip models based on induced pluripotent stem cells could provide a next generation of skin models for drug discovery and testing. PMID- 27265773 TI - Marriage trends among Americans with childhood-onset disabilities, 1997-2013. AB - BACKGROUND: People with disabilities are less likely to marry than people without disabilities. Trends in marriage and assortative mating among people with disabilities have not been investigated. HYPOTHESIS: This study tested if marriage likelihood converged between adults with childhood-onset disabilities and their peers, and if married adults with childhood-onset disabilities became more likely to have a spouse without disabilities. METHODS: U.S. data from annual National Health Interview Surveys were used to identify adults ages 18-44 surveyed between 1997 and 2013 (N = 562,229). Childhood-onset disability was defined by self-report of physical conditions limiting the respondent's activities since age <18 years. Weighted multivariate logistic regressions were used to compare trends in ever marrying and current marriage to a spouse without reported disabilities between adults with childhood-onset disabilities and adults without childhood-onset disabilities. RESULTS: Across survey years, the decline in odds of having ever married was stronger among adults with childhood-onset disabilities (OR = 0.94; 95% CI: 0.93, 0.95; p < 0.001) than among adults without childhood-onset disabilities (OR = 0.96; 95% CI: 0.96, 0.96; p < 0.001), and divergence in these trends was statistically significant (p = 0.001). Employment and college attendance were positively correlated with marriage among people with childhood-onset disabilities. Among adults married at the time of the survey, those with childhood-onset disabilities were less likely to have a spouse without reported disabilities. CONCLUSIONS: The American retreat from marriage has been accelerated among adults with childhood-onset disabilities, with high rates of in marriage to other people with disabilities persisting in this group. PMID- 27265774 TI - Stabilisation of self-assembled DNA crystals by triplex-directed photo-cross linking. AB - The tensegrity triangle is a robust DNA motif that can self-assemble to generate macroscopic three-dimensional crystals. However, the stability of these crystals is dependent on the high ionic conditions used for crystal growth. Here we demonstrate that a triplex-forming oligonucleotide can be used to direct the specific intercalation, and subsequent photo-cross-linking, of 4,5',8 trimethylpsoralen to single or multiple loci within or between the tiles of the crystal. Cross-linking between the tiles of the crystal improves their thermal stability. Such an approach is likely to facilitate the removal of crystals from their mother liquor and may prove useful for applications that require greater crystal stability. PMID- 27265775 TI - Zika virus and pregnancy. PMID- 27265776 TI - A method for improved 4D-computed tomography data acquisition. AB - In four-dimensional time-dependent computed tomography (4D-CT) of the lungs, irregularities in breathing movements can cause errors in data acquisition, or even data loss. We present a method based on sending a synthetic, regular breathing signal to the CT instead of the real signal, which ensures 4D-CT data sets without data loss. Subsequent correction of the signal based on the real breathing curve enables an accurate reconstruction of the size and movement of the target volume. This makes it possible to plan radiation treatment based on the obtained data. The method was tested with dynamic thorax phantom measurements using synthetic and real breathing patterns. PMID- 27265777 TI - The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis: A Systematic Review and Meta-analysis. AB - BACKGROUND: Patients who require dialysis are at high risk for cardiovascular mortality, which may be improved by mineralocorticoid receptor antagonists (MRAs). STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING & POPULATION: Adults undergoing long-term hemodialysis or peritoneal dialysis with or without heart failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials evaluating an MRA in dialysis and reported at least one outcome of interest. INTERVENTION: Spironolactone (8 trials) or eplerenone (1 trial) compared to placebo (7 trials) or standard of care (2 trials). OUTCOMES: Cardiovascular and all-cause mortality, hyperkalemia, serum potassium level, hypotension, change in blood pressure, and gynecomastia. RESULTS: We identified 9 trials including 829 patients. The overall quality of evidence was low due to methodologic limitations in most of the included trials. The relative risk (RR) for cardiovascular mortality was 0.34 (95% CI, 0.15-0.75) for MRA-treated compared with control patients. The RR for all-cause mortality was 0.40 (95% CI, 0.23-0.69). The RR for hyperkalemia for MRA treatment was 3.05 (95% CI, 1.21-7.70). Sensitivity analyses demonstrated wide variability in RRs for cardiovascular mortality, all-cause mortality, and hyperkalemia, suggesting further uncertainty in the confidence of the primary results. LIMITATIONS: Trial quality and size insufficient to robustly and precisely identify a treatment effect. CONCLUSIONS: Given the uncertainty of both the benefits and harms of MRAs in dialysis, large high-quality trials are required. PMID- 27265778 TI - Smart window coating based on F-TiO2-KxWO3 nanocomposites with heat shielding, ultraviolet isolating, hydrophilic and photocatalytic performance. AB - A series of smart window coated multifunctional NIR shielding-photocatalytic films were fabricated successfully through KxWO3 and F-TiO2 in a low-cost and environmentally friendly process. Based on the synergistic effect of KxWO3 and F TiO2, the optimal proportion of KxWO3 to F-TiO2 was investigated and the FT/2KWO nanocomposite film exhibited strong near-infrared, ultraviolet light shielding ability, good visible light transmittance, high photocatalytic activity and excellent hydrophilic capacity. This film exhibited better thermal insulation capacity than ITO and higher photocatalytic activity than P25. Meanwhile, the excellent stability of this film was examined by the cycle photocatalytic degradation and thermal insulation experiments. Overall, this work is expected to provide a possibility in integrating KxWO3 with F-TiO2, so as to obtain a multifunctional NIR shielding-photocatalytic nanocomposite film in helping solve the energy crisis and deteriorating environmental issues. PMID- 27265779 TI - T-peak to T-end Interval Predicts Appropriate Shocks in Patients with Heart Failure Undergoing Implantable Cardioverter Defibrillator Implantation for Primary Prophylaxis. AB - BACKGROUND: T-wave peak to T-wave end interval (Tp-e) correlates with dispersion of ventricular repolarization. The purpose of this study was to assess the ability of Tp-e to predict appropriate implantable cardioverter defibrillator (ICD) shocks and all-cause mortality in patients who underwent ICD implantation for primary prophylaxis. METHODS: Two hundred twenty-eight patients with left ventricular ejection fraction <=35% and an ICD implanted were followed-up prospectively. Patients divided into two subgroups according to presence of appropriate ICD shocks (Group 1: 112 patients with ICD shocks, Group 2: 116 patients without shocks). End points were appropriate ICD therapy due to ventricular tachycardia (VT)/ventricular fibrillation (VF), death, and a combined end point of VT/VF or death. RESULTS: During a mean follow-up of 22.3 +/- 7.7 months, appropriate ICD shocks were observed in 112 of 228 patients (49.1%). The mean duration of the Tp-e Group 1 was significantly longer than Group 2 (115.3 +/ 22.2 vs 104.7 +/- 20.2 ms, P < 0.001). Ischemic etiology and Tp-e duration were found to be independent predictors of ICD therapy. When the patients were divided into two groups based on Tp-e interval, there was no significant difference regarding the mortality between groups (21.2% vs 21.8%, P: 0.186). However, appropriate ICD shocks due to VT/VF (37.5% vs 58.8%, P < 0.001) and combined end point (39.4% vs 64.5%, P: 0.002) were significantly higher in patients with longer Tp-e group. CONCLUSIONS: Tp-e interval independently predicts appropriate ICD shocks in patients with systolic dysfunction and ICDs implanted for primary prevention. PMID- 27265780 TI - Photocatalytic Hydroxylation of Benzene by Dioxygen to Phenol with a Cyano Bridged Complex Containing Fe(II) and Ru(II) Incorporated in Mesoporous Silica Alumina. AB - Photocatalytic hydroxylation of benzene to phenol was achieved by using O2 as an oxidant as well as an oxygen source with a cyano-bridged polynuclear metal complex containing Fe(II) and Ru(II) incorporated in mesoporous silica-alumina ([Fe(H2O)3]2[Ru(CN)6]@sAl-MCM-41). An apparent turnover number (TON) of phenol production per the monomer unit of [Fe(H2O)3]2[Ru(CN)6] was 41 for 59 h. The cyano-bridged polynuclear metal complex, [Fe(H2O)3]2[Ru(CN)6], exhibited catalytic activity for thermal hydroxylation of benzene by H2O2 in acetonitrile (MeCN), where the apparent TON of phenol production reached 393 for 60 h. The apparent TON increased to 2500 for 114 h by incorporating [Fe(H2O)3]2[Ru(CN)6] in sAl-MCM-41. Additionally, [Fe(H2O)3]2[Ru(CN)6] acts as a water oxidation catalyst by using [Ru(bpy)3](2+) (bpy = 2,2'-bipyridine) and Na2S2O8 as a photosensitizer and a sacrificial electron acceptor as evidenced by (18)O-isotope labeling experiments. Photoirradiation of an O2-saturated MeCN solution containing [Fe(H2O)3]2[Ru(CN)6]@sAl-MCM-41 and scandium ion provided H2O2 formation, where photoexcited [Ru(CN)6](4-) moiety reduces O2 as indicated by laser flash photolysis measurements. Thus, hydroxylation of benzene to phenol using molecular oxygen photocatalyzed by [Fe(H2O)3]2[Ru(CN)6] occurred via a two-step route; (1) molecular oxygen was photocatalytically reduced to peroxide by using water as an electron donor, and then (2) peroxide thus formed is used as an oxidant for hydroxylation of benzene. PMID- 27265782 TI - The expression of methiopropamine-induced locomotor sensitization requires dopamine D2, but not D1, receptor activation in the rat. AB - Methiopropamine (MPA) is a structural analog to methamphetamine and is categorized as a novel psychoactive substance that needs to be controlled. However, no study has been performed to determine whether MPA actually develops an addiction-like behavior similar to those arising from other psychomotor stimulants. Thus, we attempted to determine whether MPA produces locomotor sensitization in a manner similar to amphetamine. In the first experiment, rats were pre-exposed to either saline or one of three different doses of MPA (0.2, 1.0, or 5.0mg/kg, IP) with a total of four injections, respectively. After a 2 week withdrawal period, when they were challenged with the same dose of MPA, only the group that was pre-exposed to high dose of MPA (5.0mg/kg) showed sensitized locomotor activity. In the second experiment, all rats were pre-exposed to MPA (5.0mg/kg) only. Interestingly, the expression of MPA-induced locomotor sensitization was inhibited by a pre-injection of a dopamine D2 receptor antagonist, eticlopride (0.05mg/kg, IP), though not by a dopamine D1 receptor antagonist, SCH23390 (0.01mg/kg, IP). These results suggest that repeated injection of MPA in the rat provokes certain neuronal changes involving specific, likely D2, dopamine receptor-mediated pathways that contribute to the expression of MPA-induced locomotor sensitization. PMID- 27265781 TI - Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission. AB - Synaptic vesicle glycoprotein 2A (SV2A) is a prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release. SV2A also serves as a specific binding site for certain antiepileptics and is implicated in the treatment of epilepsy. Here, to elucidate the role of SV2A in modulating epileptogenesis, we generated a novel rat model (Sv2a(L174Q) rat) carrying a Sv2a targeted missense mutation (L174Q) and analyzed its susceptibilities to kindling development. Although animals homozygous for the Sv2a(L174Q) mutation exhibited normal appearance and development, they are susceptible to pentylenetetrazole (PTZ) seizures. In addition, development of kindling associated with repeated PTZ treatments or focal stimulation of the amygdala was markedly facilitated by the Sv2a(L174Q) mutation. Neurochemical studies revealed that the Sv2a(L174Q) mutation specifically reduced depolarization-induced GABA, but not glutamate, release in the hippocampus without affecting basal release or the SV2A expression level in GABAergic neurons. In addition, the Sv2a(L174Q) mutation selectively reduced the synaptotagmin1 (Syt1) level among the exocytosis-related proteins examined. The present results demonstrate that dysfunction of SV2A due to the Sv2a(L174Q) mutation impairs the synaptic GABA release by reducing the Syt1 level and facilitates the kindling development, illustrating the crucial role of SV2A GABA system in modulating kindling epileptogenesis. PMID- 27265783 TI - Increased neuroplasticity and hippocampal microglia activation in a mice model of rapid antidepressant treatment. AB - The search for biomarkers of antidepressant effects focused on pathways regulating synaptic plasticity, and on activated inflammatory markers. Repeated Sleep Deprivation (SD) provides a model treatment to reverse-translate antidepressant effects from in vivo clinical psychiatry to model organisms. We studied the effects of repeated SD alone (ASD) or combined with exercise on a slow spinning wheel (SSW), in 116 C57BL/6J male mice divided in three groups (ASD, SSW, untreated). Forced Swimming Test (FST) was used to detect antidepressant-like effects. Unbiased evaluation of the transcriptional responses were obtained in the hippocampus by Illumina Bead Chip Array system, then confirmed with real time PCR. Spine densities in granular neurons of the dentate gyrus (DG) were assayed by standard Golgi staining. Activation of Microglial/Macrophages cells was evaluated by immunufluorescence analysis for Iba1. Rates of cell proliferation was estimated pulsing mice with the S-phase tracer 5-Iodo-2'-deoxyuridine (IdU). All SD procedures caused a decreasing of floating time at FST, and increased expression of the immediate early gene Arc/Arg3.1. In addition, SSW also increased expression of the Microglia/Macrophages genes Iba-1 and chemokine receptors Cx3cR1 and CxcR4, of the canonical Wnt signaling gene Wnt7a, and of dendritic spines in CA4 neurons of the DG. SSW up-regulated both the number of Iba1+ cells and rates of cell proliferation in the subgranular region of the DG. The antidepressant-like effects of SD dissociated both, from hippocampal neuroplasticity in the DG (not occurring after ASD), and from microglial activation (not preventing behavioral response when occurring). The increase in dendritic spine density in the DG after SD and exercise was associated with an up-regulation of Wnt 7a, and with activation of the innate immune system of the brain. Increased Arc/Arg3.1 suggests however increased neuroplasticity, which could be common to all fast acting antidepressants, and possibly occurring in other brain areas. PMID- 27265784 TI - Infliximab ameliorates AD-associated object recognition memory impairment. AB - Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of Abeta oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of Abeta oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-alpha, visual recognition memory impaired by pre-administered Abeta oligomers dramatically improved and the detrimental Abeta effect on mAChR-LTD was annulled. Taken together, these findings suggest that Abeta-induced inflammation is mediated through TNF-alpha signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits. PMID- 27265786 TI - Association of expression levels of pluripotency/stem cell markers with the differentiation outcome of Wharton's jelly mesenchymal stem cells into insulin producing cells. AB - Recently, there has been much attention towards generation of insulin producing cells (IPCs) from stem cells, especially from Wharton's jelly mesenchymal stem cells (WJ-MSCs). However, generation of mature IPCs remains a challenge. Assessment of generation of IPCs was usually done by examining beta-cell markers, however, assessment of pluripotency/stem cell markers drew less attention. Therefore, the purpose of this study was to investigate the levels of pluripotency/stem cell markers during differentiation of WJ-MSCs into IPCs and the association of these levels with differentiation outcomes. WJ-MSCs were isolated, characterized then induced to differentiate into IPCs using three different protocols namely A, B and C. Differentiated IPCs were assessed by the expression of pluripotency/stem cell markers, together with beta-cell markers using qRT-PCR, and functionally by measuring glucose stimulated insulin secretion. Differentiated cells from protocol A showed lowest expression of pluripotency/stem cell markers and relatively best GSIS. However, protocol B showed concomitant expression of pluripotency/stem cell and beta-cell markers with relatively less insulin secretion as compared to protocol A. Protocol C failed to generate glucose-responsive IPCs. In conclusion, sustained expression of pluripotency/stem cell markers could be associated with the incomplete differentiation of WJ-MSCs into IPCs. A novel finding for which further investigations are warranted. PMID- 27265787 TI - Thymoquinone, an active constituent of Nigella sativa seeds, binds with bilirubin and protects mice from hyperbilirubinemia and cyclophosphamide-induced hepatotoxicity. AB - Some reports indicate that thymoquinone (TQ), the main constituent of Nigella sativa seeds, is hepatoprotective. The aim of this study was to determine whether TQ is able to bind directly to bilirubin, and whether TQ or liposomal formulation of TQ (Lip-TQ) can reduce cyclophosphamide (CYP)-induced liver toxicity, serum bilirubin level in mice. The binding of TQ with bilirubin was studied by UV-VIS, fluorescence and Near-UV CD spectroscopy. Inhibition of binding of bilirubin to erythrocytes by TQ was also examined. To increase the in vivo efficacy, Lip-TQ was prepared and used against CYP-induced toxicity. The protective role of TQ or Lip-TQ against CYP-induced toxicity was assessed by determining the liver function parameters, the levels of superoxide dismutase (SOD) and catalase (CAT), and histological studies. It was found that TQ binds to bilirubin and significantly inhibits the binding of bilirubin to erythrocytes. Lip-TQ (10 mg/kg) significantly reduced the levels of aspartate transaminase (AST) from 254 +/- 48 to 66 +/- 18 IU/L (P < 0.001), alanine transaminase (ALT) from 142 +/- 28 to 47.8 +/- 16 IU/L (P < 0.05) and serum bilirubin from 2.8 +/- 0.50 to 1.24 +/- 0.30 mg/dl (P < 0.05). Treatment with Lip-TQ reduced the CYP-induced inflammation and hemorrhage in liver tissues. Moreover, treatment with free or Lip-TQ protected the activity of SOD and CAT in CYP-injected mice. Therefore, TQ can reduce the level of bilirubin in systemic circulation in disease conditions that lead to hyperbilirubinemia and liver toxicity and hence may be used as a supplement in the treatment of liver ailments. PMID- 27265785 TI - Hippocampal proteomics defines pathways associated with memory decline and resilience in normal aging and Alzheimer's disease mouse models. AB - Alzheimer's disease (AD), the most common form of dementia in the elderly, has no cure. Thus, the identification of key molecular mediators of cognitive decline in AD remains a top priority. As aging is the most significant risk factor for AD, the goal of this study was to identify altered proteins and pathways associated with the development of normal aging and AD memory deficits, and identify unique proteins and pathways that may contribute to AD-specific symptoms. We used contextual fear conditioning to diagnose 8-month-old 5XFAD and non-transgenic (Ntg) mice as having either intact or impaired memory, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify hippocampal membrane proteins across groups. Subsequent analysis detected 113 proteins differentially expressed relative to memory status (intact vs impaired) in Ntg mice and 103 proteins in 5XFAD mice. Thirty-six proteins, including several involved in neuronal excitability and synaptic plasticity (e.g., GRIA1, GRM3, and SYN1), were altered in both normal aging and AD. Pathway analysis highlighted HDAC4 as a regulator of observed protein changes in both genotypes and identified the REST epigenetic regulatory pathway and Gi intracellular signaling as AD specific pathways involved in regulating the onset of memory deficits. Comparing the hippocampal membrane proteome of Ntg versus AD, regardless of cognitive status, identified 138 differentially expressed proteins, including confirmatory proteins APOE and CLU. Overall, we provide a novel list of putative targets and pathways with therapeutic potential, including a set of proteins associated with cognitive status in normal aging mice or gene mutations that cause AD. PMID- 27265788 TI - Template Synthesis, Metalation, and Self-Assembly of Protic Gold(I)/(NHC)2 Tectons Driven by Metallophilic Interactions. AB - A new protocol for the synthesis of protic bis(N-heterocyclic carbene) complexes of Au(I) by a stepwise metal-controlled coupling of isocyanide and propargylamine is described. They are used as tectons for the construction of supramolecular architectures through metalation and self-assembly. Notably a unique polymeric chain of Cu(I) with alternate Au(I) /bis(imidazolate) bridging scaffolds and strong unsupported Cu(I) -Cu(I) interactions has been generated, as well as a 28 metal-atoms cluster containing a nanopiece of Cu2 O trapped by peripheral Au(I) /bis(imidazolate) moieties. PMID- 27265790 TI - A novel approach to treatment in childhood acute myeloblastic leukemia and myelodysplastic syndrome with high-dose methylprednisolone as a differentiation- and apoptosis-inducing agent of myeloid leukemic cells. AB - Differentiation-inducing therapy with all-trans retinoic acid significantly improved the outcome in children with acute promyelocytic leukemia (APL). Therefore, use of agents that induce differentiation of leukemic cells in non-APL children appears to be a highly promising therapeutic approach. Based on the experimental studies in mice, we have shown that short-course high-dose methylprednisolone (HDMP) treatment can induce terminal differentiation of leukemic cells in children with various subtypes of acute myeloblastic leukemia (AML-M1,-M2,-M3,-M4,-M7). It has also been shown to induce apoptosis of myeloid leukemic cells with or without differentiation. Administration of HDMP as a single agent resulted in a rapid clinical improvement, a marked decrease in blast cells in both peripheral blood and bone marrow and dramatic decreases in the size of extramedullary leukemic mass in children with AML and myelodysplastic syndrome (MDS). Addition of HDMP to cytotoxic chemotherapy regimens increased the remission rate and improved the outcome in these children. Future clinical trials with HDMP would contribute to further improvements in the treatment results in these children. PMID- 27265789 TI - A three dimensional nerve map of human bladder trigone. AB - AIM: Central efferent and afferent neural pathways to and from the human urinary bladder are well-characterized, but the location and arborization of these nerves as they traverse the serosa, muscularis, and urothelial layers are not clearly defined. The purpose of this study was to create a three dimensional map of the innervation of the human bladder trigone from the extrinsic perivesical adventitial nerve trunks to the urothelium. METHODS: A male and a female human bladder were harvested from fresh frozen cadavers and fixed in formalin. The bladder neck and trigone region were serially sectioned (5 MUm) and every 20th slide was stained (S100), scanned and aligned to create 3D maps. RESULTS: Nerve penetration into the detrusor muscle occurs with the highest frequency at the bladder neck and interureteric ridge. Nerves traveling parallel to the bladder lumen do so in the adventitia, beyond the outer border of detrusor. In females, the depth of these nerve bands is uniform at 0.7-1.7 cm below the luminal surface, the outer limits of which include the anterior vaginal wall. In the male, depth is more variable owing to detrusor hypertrophy with the minimum depth of nerves approximately 0.5 cm near the interureteric ridge and over 1 cm near the bladder neck. CONCLUSIONS: Myelinated neural pathways traversing in the human bladder in the region of the trigone have a discreet regional density. This 3D map of trigonal innervation may provide guidance to more precisely direct therapies for urinary incontinence or pelvic pain. Neurourol. Urodynam. 36:1015 1019, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27265791 TI - Mixed chimerism following hematopoietic stem cell transplantation in pediatric thalassemia major patients: a single center experience. AB - OBJECTIVE: Stable mixed chimerism (MC) may result in cure for thalassemia major patients following hematopoietic stem cell transplantation (HSCT), but rejection can occur. Twenty-eight HSCTs for thalassemia major were reviewed retrospectively to evaluate the clinical course of MC with possible risk factors and predictors of outcome, with a median follow-up of 1669 days (811-3576 days). METHODS: Chimerism was detected by fluorescence in situ hybridization (FISH) or multiplex polymerase chain reaction depending on the sex match between the donor and the recipient. RESULTS: Primary rejection, stable MC and full donor chimerism was detected in 3.6%, 17.8% and 78.6% of patients, respectively. Clinically, 4/5 patients with stable MC had thalassemia trait with donor chimerism as low as 14%. One patient was started on pRBC transfusions at 2.5 years postHSCT. CONCLUSION: Stable MC can result in cure for thalassemia major patients. The clinical picture remains as the best guide for intervention until a more reliable predictor is available. PMID- 27265792 TI - Association of FXII 5'UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease. AB - OBJECTIVE: Thrombotic diseases are caused by genetic and environmental factors. There are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that FXII is involved in pathogenesis of thrombophilic diseases. However, the results in this regard are highly controversial. Plasma FXII activity levels are strongly determined by a 46CgammaT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated in a case-control study. METHODS: One hundred and sixty subjects were studied: 120 patients diagnosed with thrombophilia (96 venous thromboembolism, 24 arterial thrombosis), and 40 age-gender-matched controls. For each subject, FXII activity level was measured by a one-step clotting assay with FXII-deficient plasma, and 46CgammaT polymorphism was genotyped using a restriction fragment length polymorphism (RFLP) method. RESULTS: In this study, the previous observation that individuals with different genotypes for the 46 CgammaT polymorphism showed significant differences in Factor XII activity levels was confirmed. Most importantly, FXII activity <= 68% was associated with an increased risk of venous thrombosis with an adjusted OR of 4.7 (95%CI= 1.03-21.1, P=0.04). However, it was not a risk factor for arterial thrombosis with adjusted OR of 5 (95%CI= 0.91 27.1, P=0.09). In CT and TT genotype the adjusted ORs were respectively 2 (95%CI=0.9-4.4, P=0.11) and 2.3 (95%CI=0.45-11, P=0.48) for patients with venous thrombosis compared with the controls. Similarly, the adjusted ORs in arterial thrombosis were 1.2 (95%CI=0.4-3.6, P=0.76) for CT and 1.8 (95%CI=0.2-14.9, P=0.59) for TT genotype. Thus, we did not find any association of the mutated T allele in the heterozygous or homozygous state with an increased risk of both venous and arterial thrombosis. CONCLUSION: Lower FXII activity is not a risk factor; rather, it simply represents a risk marker for thrombosis. PMID- 27265793 TI - Hospital-acquired pneumonia in patients receiving immunosuppressive therapy. AB - OBJECTIVE: The aims of this study were to determine the clinical success rates, effect of neutropenia on treatment success rates, risk factors related to mortality, and survival in patients who developed hospital-acquired pneumonia (HAP) while receiving immunosuppressive therapy. METHODS: Forty-three adult patients receiving immunosuppressive therapy who developed HAP were included in this prospective study. Transplantation patients and human immunodeficiency virus (HIV)-positive patients were not included. Antibiotic treatment was managed by a multidisciplinary team. The Kaplan Meier method was used for the survival analysis and Cox regression was used for the identification of mortality-related independent risk factors. The relationship between neutropenia and the clinical success rate was determined using the chi-square test. RESULTS: Although anti pseudomonal antibiotics were started empirically in 40 of the 43 patients (93%) at the beginning of the treatment, the most frequently isolated pathogens were Acinetobacter spp. and Escherichia coli. The success rate at the end of the treatment was 65.1%. The survival rates for the 3rd, 14th, 42nd, and 365th days were 97%, 86%, 58%, and 19%, respectively. Elevated levels of urea [Hazard Ratio=1.01 (95% CI: 1.00-1.02)] and blood glucose [HR=1.01 (95% CI: 1.00-1.02)] were found to be independent risk factors affecting survival. The treatment success rate was higher in patients without neutropenia (n=23) than in those with neutropenia (n=20) (p=0.05). CONCLUSION: The treatment success rate was low in patients who developed HAP while receiving immunosuppressive therapy. PMID- 27265794 TI - Sonographic evaluation of spleen size and prevalence of accessory spleen in a healthy male Turkish population. AB - OBJECTIVE: It is known that the measurement of splenic length in routine clinical practice is a very good indicator of actual splenic size. Knowledge of the normal range of spleen size in the population being examined is a prerequisite. Racial differences in splenic length could result in incorrect interpretation of splenic measurements. The purpose of this study was to establish the range of spleen length in a young male Turkish population. METHODS: A total of 2179 volunteers, healthy men aged 17-42 years, from the annual Army Reserve Officer Training Corps training camp at Manisa were included in the study. Sonographic measurements of spleen length were performed on 2179 military personnel. Presence of accessory spleen was also determined. In addition, the height, weight, and age of each volunteer were recorded. Using linear regression analysis, the relation of spleen length and body height, weight and body mass index (BMI) was evaluated. Additionally, the prevalence of accessory spleen detected on ultrasound was calculated. RESULTS: The mean+/-SD height was 173,1+/-6,5 cm, mean weight 69,1+/ 9,7 kg, and mean BMI 22,62+/-2,87. Mean spleen length was 10,76+/-1,8 cm. The length of the spleen was below 12,80 cm in 95% of the subjects. No statistically significant correlation (p<0.01) between spleen length and body height, weight and BMI was found. The prevalence of accessory spleen was determined as 2.5% on ultrasound screening. CONCLUSION: It was found that in healthy Turkish men, mean spleen length was 10,76+/-1,8 cm. This data should be taken into consideration when the diagnosis of splenomegaly is established in Turkish males. PMID- 27265795 TI - Non-Hodgkin's lymphoma with bone involvement: a single center experience with 18 patients. AB - OBJECTIVE: Non-Hodgkin's lymphoma (NHL) of bone is a rare entity. The most common histological subtype is diffuse large B cell lymphoma (DLBCL). The major presenting symptoms are soft tissue swelling, bone pain and pathological fracture. Treatment options are chemotherapy, radiotherapy, surgery, or a combination of these modalities. METHODS: We retrospectively analyzed the 18 patients (11 females, 7 males) with NHL of bone who were diagnosed and treated between 1995-2005. The median age was 56.5 years. The median duration of symptoms was 4.5 months. The bone pain was the first symptom in all patients. Tru-cut biopsy was performed for diagnosis in most of the cases. Diagnosis in five patients (27.8%) required open biopsy. RESULTS: DLBCL (77.8%) was the most common histological type among all patients. Other histological subtypes were anaplastic large cell lymphoma (11.1%), Burkitt-like lymphoma (5.6%) and marginal zone lymphoma (5.6%). According to Ann Arbor staging system, 44.4% of patients were Stage I, 11.1% were Stage II and 44.4% were Stage IV. Bone marrow involvement was determined in four patients (22.2%). All patients except one were treated with anthracycline-containing regimens and eight patients (44.4%) received rituximab combination with chemotherapy. Radiation therapy was performed as the first-line therapy in 9 (50%) patients. The median follow-up was 37 months (range, 2-124 months). Among the 17 patients who achieved complete remission, five (27.8%) relapsed. All patients were still alive. The five-year relapse-free survival was 73.5%. CONCLUSION: The treatment of bone lymphoma can be planned according to the stage and location of the disease. Although we had a relatively low number of patients, it could be concluded that whether or not radiation therapy is performed, rituximab in combination with systemic chemotherapy has been proven beneficial on survival. PMID- 27265796 TI - Early detection of pulmonary fungal infection by CT scan in pediatric ALL patients under chemotherapy or in post-transplantation period with primary complaint of chest pain. AB - We describe herein four children with acute lymphoblastic leukemia who were diagnosed as pulmonary fungal infection after presenting with chest pain. The plain radiologic evaluations failed to reveal any positive findings, whereas computerized tomography (CT) scanning showed nodular opacification with or without cavitation. This experience suggests that chest pain may be an initial symptom of an invasive fungal infection in patients with leukemia, and CT scan of the lungs should be performed urgently for the early diagnosis and treatment, despite normal plain X-rays. PMID- 27265797 TI - Aplastic anemia presenting as hemophagocytic lymphohistiocytosis. AB - Two unusual cases of hemophagocytic lymphohistiocytosis (HLH) complicating aplastic anemia (AA) are described. Each patient had a history of preexisting acute hepatitis of unknown cause at the time of HLH diagnosis and infection associated secondary HLH. They developed high fever and pancytopenia. Hemophagocytes were seen in the bone marrow. With steroid (in combination with etoposide and CyA in 1 patient), high fever disappeared and the patients' liver function gradually recovered. As severe pancytopenia persisted, bone marrow became acellular and AA was diagnosed. Since HLH is known to be able to cause an aplastic bone marrow if untreated for a prolonged time, it is therefore in line that hepatitis-associated AA may also be associated with HLH. Aplastic anemia associated HLH has been reported rarely, and problems in the diagnostic procedure are discussed. PMID- 27265798 TI - Unusual cytochemical reactivity for toluidine blue in granular acute lymphoblastic leukemia: a report of two rare cases. AB - Azurophilic granulation of blasts is a feature of acute myeloid leukemia (AML). Granular acute lymphoblastic leukemia (ALL) may mimic AML due to the presence of cytoplasmic granules in lymphoblasts, but cytochemistry and immunophenotyping are helpful in making the correct diagnosis. Toluidine blue (TB) is a metachromatic dye, which stains basophils and myeloid blasts that exhibit basophilic differentiation. Reactivity for TB has not been described in lymphoblasts. We herein report two cases of granular ALL with blasts exhibiting reactivity for TB that caused diagnostic dilemma. Immunophenotyping and cytogenetic studies were helpful in making a correct diagnosis. This report of two rare case highlight the reactivity of lymphoblasts with TB not hitherto described and the importance of a detailed diagnostic work-up in acute leukemia. PMID- 27265799 TI - Primary cutaneous diffuse large B-Cell lymphoma, leg type. PMID- 27265800 TI - A note on oseltamivir treatment in a boy with G6PD deficiency. PMID- 27265801 TI - Malignancy-associated hemophagocytosis in children. PMID- 27265802 TI - Leukocytosis, thrombocytosis and hypercalcemia as a triple paraneoplastic syndrome in a patient with squamous cell carcinoma of the renal pelvis. PMID- 27265803 TI - Nitric oxide in beta-thalassemia minor: what factors contribute? PMID- 27265804 TI - Acute tumor lysis syndrome secondary to a single-dose methylprednisolone in acute lymphoblastic leukemia. PMID- 27265805 TI - A potential role for glia-derived extracellular matrix remodeling in postinjury epilepsy. AB - Head trauma and vascular injuries are known risk factors for acquired epilepsy. The sequence of events that lead from the initial injury to the development of epilepsy involves complex plastic changes and circuit rewiring. In-depth, comprehensive understanding of the epileptogenic process is critical for the identification of disease-modifying targets. Here we review the complex interactions of cellular and extracellular components that may promote epileptogenesis, with an emphasis on the role of astrocytes. Emerging evidence demonstrates that astrocytes promptly respond to brain damage and play a critical role in the development of postinjury epilepsy. Astrocytes have been shown to regulate extracellular matrix (ECM) remodeling, which can affect plasticity and stability of synapses and, in turn, contribute to the epileptogenic process. From these separate lines of evidence, we present a hypothesis suggesting a possible role for astrocyte-regulated remodeling of ECM and perineuronal nets, a specialized ECM structure around fast-spiking inhibitory interneurons, in the development and progression of posttraumatic epilepsies. (c) 2016 Wiley Periodicals, Inc. PMID- 27265806 TI - Safety and Efficacy of High-Dose Unfractionated Heparin for Prevention of Venous Thromboembolism in Overweight and Obese Patients. AB - STUDY OBJECTIVE: To determine the safety and efficacy of high-dose subcutaneous unfractionated heparin (UFH) for prevention of venous thromboembolism (VTE) in overweight and obese patients. DESIGN: Single-center retrospective observational cohort study. SETTING: Large academic tertiary care medical center. PATIENTS: A total of 1335 adults who weighed more than 100 kg on admission and received either subcutaneous UFH 7500 units every 8 hours (751 patients [high-dose group]) or 5000 units every 8 hours (584 patients [low-dose group]) for VTE prophylaxis during their hospitalization between January 1, 2013, and August 31, 2014. MEASUREMENTS AND MAIN RESULTS: The incidences of VTE and bleeding complications were assessed in each group. Each group was further divided into four groups based on their body mass index (BMI): overweight (BMI 25-29.9 kg/m(2) ), obese class I (BMI 30-34.9 kg/m(2) ), obese class II (BMI 35-39.9 kg/m(2) ), and obese class III (BMI >= 40 kg/m(2) ). The incidence of VTE was similar for patients in the high-dose group versus those in the low-dose group for all BMI categories. Bleeding complications were significantly higher for patients in the high-dose group. The proportion of patients with at least a 2-g/dl hemoglobin drop from admission was higher in patients in the high-dose groups in obese classes II and III: obese class II, 46 (30%) of 152 patients in the high-dose group versus 30 (18%) of 171 patients in the low-dose group (p<0.01); obese class III, 109 (25%) of 432 patients in the high-dose group versus 31 (12%) of 249 patients in the low dose group (p<0.01). In addition, the proportion of patients who received at least 2 units of packed red blood cell transfusion was significantly higher in patients in the high-dose group who were in obese class III: 47 (11%) of 432 in the high-dose group versus 13 (5%) of 249 in the low-dose group (p<0.01). CONCLUSION: Administering a higher dose of heparin to patients weighing more than 100 kg may not impart additional efficacy in reducing the incidence of VTE. However, it may increase the risk for bleeding. PMID- 27265807 TI - Effects of hirami lemon, Citrus depressa Hayata, leaf meal in diets on the immune response and disease resistance of juvenile barramundi, Lates calcarifer (bloch), against Aeromonas hydrophila. AB - The present study was conducted to evaluate the dietary supplementation of leaf meal from Citrus depressa Hayata on the growth, innate immune response, and disease resistance of juvenile barramundi, Lates calcarifer. Four diets were formulated to contain 0% (control), 1% (C1), 3% (C3), and 5% (C5) leaf meal, respectively. During a 56 d feeding trial, fish survival, growth performance, and feed efficiency were not significantly different among all groups. For immune response, respiratory burst, superoxide dismutase and lysozyme activities were not significantly different among all groups. However, fish fed the C5 diet for 56 d had significantly higher phagocytic activity. Also, fish fed C3 and C5 diets had significantly higher Mx gene expressions in spleens and head kidneys with nerve necrosis virus injections after 24 h. Disease resistance against Aeromonas hydrophila was increased by the C5 diet. In this study, barramundi fed on a diet containing 5% C. depressa Hayata leaf meal had significantly better innate immune response and disease resistance against A. hydrophila. PMID- 27265808 TI - The dynamic relationship between cerebellar Purkinje cell simple spikes and the spikelet number of complex spikes. AB - KEY POINTS: Purkinje cells are the sole output of the cerebellar cortex and fire two distinct types of action potential: simple spikes and complex spikes. Previous studies have mainly considered complex spikes as unitary events, even though the waveform is composed of varying numbers of spikelets. The extent to which differences in spikelet number affect simple spike activity (and vice versa) remains unclear. We found that complex spikes with greater numbers of spikelets are preceded by higher simple spike firing rates but, following the complex spike, simple spikes are reduced in a manner that is graded with spikelet number. This dynamic interaction has important implications for cerebellar information processing, and suggests that complex spike spikelet number may maintain Purkinje cells within their operational range. ABSTRACT: Purkinje cells are central to cerebellar function because they form the sole output of the cerebellar cortex. They exhibit two distinct types of action potential: simple spikes and complex spikes. It is widely accepted that interaction between these two types of impulse is central to cerebellar cortical information processing. Previous investigations of the interactions between simple spikes and complex spikes have mainly considered complex spikes as unitary events. However, complex spikes are composed of an initial large spike followed by a number of secondary components, termed spikelets. The number of spikelets within individual complex spikes is highly variable and the extent to which differences in complex spike spikelet number affects simple spike activity (and vice versa) remains poorly understood. In anaesthetized adult rats, we have found that Purkinje cells recorded from the posterior lobe vermis and hemisphere have high simple spike firing frequencies that precede complex spikes with greater numbers of spikelets. This finding was also evident in a small sample of Purkinje cells recorded from the posterior lobe hemisphere in awake cats. In addition, complex spikes with a greater number of spikelets were associated with a subsequent reduction in simple spike firing rate. We therefore suggest that one important function of spikelets is the modulation of Purkinje cell simple spike firing frequency, which has implications for controlling cerebellar cortical output and motor learning. PMID- 27265809 TI - Study of retinal alterations in a high fat diet-induced type ii diabetes rodent: Meriones shawi. AB - Diabetic retinopathy is a common complication of type 2 diabetes and the leading cause of blindness in adults of working age. The aim of this work was to study the repercussions of high fat diet (HFD) induced diabetes on the retina of Meriones shawi (M.sh). Two groups of six M.sh each was studied. Group I was a normal control, fed with standard laboratory granules. In Group II, rodents received a HFD of enriched laboratory granules, for a period of 3 months. Body weight and plasma glucose were determined in the two groups. Retinal sections of the two groups were stained with the Hematoxylin-Eosin. Photoreceptors were identified by immunolabeling for rhodopsin (rods) and PNA (cones). Gliosis and microglial activation were identified by immunolabeling for GFAP and Iba-1. Labeling of calretinin and parvalbumin were also carried out to study the AII amacrine cells. Retinal layers thicknesses, gliosis, and specific neural cell populations were quantified by microscopy. The body weight (+77%) and plasma glucose (+108%) were significantly greater in the HFD rodents. Three months of HFD induced a significant loss of 38.77% of cone photoreceptors, as well as gliosis and an increase of 70.67% of microglial cells. Calcium homeostatic enzymes were depleted. This work shows that HFD in Meriones shawi induces a type II diabetes-like condition that causes loss of retinal neurons and photoreceptors, as well as gliosis. Meriones shawi could be a useful experimental animal model for this physiopathology particularly in the study of retinal neuro glial alterations in Type II diabetes. PMID- 27265810 TI - A 3-month age difference profoundly alters the primary rat stromal vascular fraction phenotype. AB - The stromal vascular fraction (SVF) is a heterogeneous population obtained from collagenase digestion of adipose tissue. When cultured the population becomes more homogeneous and the cells are then termed adipose stromal/stem cells (ASCs). Both the freshly isolated primary SVF population and the cultured ASC population possess regenerative abilities suggested to be mediated by paracrine mechanisms mainly. The use of ASCs and SVF cells, both in animal studies and human clinical studies, has dramatically increased during recent years. However, more knowledge regarding optimal donor characteristics such as age is demanded. Here we report that even a short age difference has an impact on the phenotype of primary SVF cells. We observed that a 3-month difference in relatively young adult rats affects the expression pattern of several mesenchymal stem cell markers in their primary SVF. The younger animals had significantly more CD90+/CD44+/CD29+/PDGFRalpha+primary cells, than the aged rats, suggesting an age dependent shift in the relative cell type distribution within the population. Taken together with recent studies of much more pronounced age differences, our data strongly suggest that donor age is a very critical parameter that should be taken into account in future stem cell studies, especially when using primary cells. PMID- 27265811 TI - The expression of KRT2 and its effect on melanogenesis in alpaca skins. AB - In order to investigate the effects of the keratin 2 (KRT2) on alpaca melanocyte in vivo and vitro, the immunohistochemistry (IHC), quantitative real-time PCR (qPCR), Western blot, and alpaca melanocytes transfection methods were used. The results showed that mRNA and protein expression of KRT2 was highly expressed in brown skin in comparison with that in white skin. Moreover, we found that KRT2 was expressed in alpaca melanocytes in vitro by immunocytochemistry. After transfection with KRT2 in alpaca melanocytes, the relative mRNA and protein expression of KRT2, microphthalmia-associtated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1) in alpaca skin melanocytes was increased with significant differences; a further result was the increase of melanin production. The results suggested that KRT2 functions in alpaca hair color formation, which offered an essential theoretical basis for further exploration of the role of melanogenesis. PMID- 27265812 TI - Significant Morbidity and Mortality Among Hospitalized End-Stage Liver Disease Patients in Medicare. AB - CONTEXT: For end-stage liver disease (ESLD) patients, care focuses on managing the life-threatening complications of portal hypertension, causing high resource utilization. OBJECTIVES: To describe the end-of-life trajectory of hospitalized ESLD patients in Medicare. METHODS: Using a 5% random sample of Medicare fee-for service beneficiaries, we performed a retrospective cohort study, identifying hospitalized ESLD and heart failure (HF) patients (2007-2011). Index hospitalization end points included mortality, discharge to hospice, and length of stay. Postdischarge end points included all-cause mortality, rehospitalization, hospice enrollment, and days alive and out of hospital (DAOH). Follow-up was at one and three years after index hospitalization discharge. A reference cohort of decompensated HF patients was used for baseline comparison. RESULTS: At one year, the ESLD cohort (n = 22,311) had 209 DAOH; decompensated HF (n = 85,397) had 252 DAOH. Among ESLD patients, inpatient mortality was 13.5%; all-cause mortality was 64.9%. For these outcomes, rates were higher in those with ESLD than HF. In the ESLD group, rehospitalization rate was 59.1% (slightly lower than the HF group), hospice enrollment rate was 36.1%, and there were higher than expected cancer rates. For hospice-enrolled patients, the median length of time spent in hospice was nine days. The HF cohort had lower hospice enrollment, but more days enrolled. CONCLUSION: The results of this study show that morbidity and mortality rates associated with end of life in ESLD are substantial. There is an acute need for alternative approaches to manage the care of ESLD patients. PMID- 27265813 TI - Factors Affecting Patients' Preferences for and Actual Discussions About End-of Life Care. AB - CONTEXT: Discussions about end-of-life care are often difficult for patients and clinicians, and inadequate communication poses a barrier to patients receiving the care they desire. OBJECTIVES: To understand factors that facilitate end-of life care discussions that guide interventions to improve care. METHODS: We examined baseline data from an ongoing randomized trial to evaluate associations between patients' self-reported desire for, and occurrence of, discussions about end-of-life care and factors influencing these discussions. Factors included emotional symptoms and barriers and facilitators to discussions. The sample included patients with serious illness (n = 473) and their primary or specialty care clinicians (n = 128). Regression analyses were adjusted for confounders and clustered patients under clinicians. RESULTS: Patients who endorsed each of three barriers to discussions were less likely to have had a discussion with their clinician (P-values ranging from <0.001 to 0.046). One facilitator (having had family/friends who died) was associated with past discussions (P = 0.037), and two facilitators were associated with wanting future discussion (P < 0.001): 1) concerns about future quality of life, 2) worries about being a burden on friends/family. Depression and anxiety were not associated with past discussions. However, patients with more anxiety were more likely to want future discussions (P = 0.001), as were patients with more depressive symptoms who had had discussions in the past (P < 0.001). CONCLUSION: The occurrence of, and desire for, patient-clinician communication about end-of-life care is associated with patient factors including communication barriers and facilitators and symptoms of depression and anxiety. Understanding these factors may facilitate design of effective communication interventions. PMID- 27265814 TI - Family Caregiver Depressive Symptom and Grief Outcomes From the ENABLE III Randomized Controlled Trial. AB - CONTEXT: Little is known about whether early palliative care (EPC) support for family caregivers (CGs) impacts depressive symptoms and grief after care recipients die. OBJECTIVES: To assess after-death CG depressive symptom and grief scores for early compared to delayed group CGs. METHODS: We conducted a randomized controlled trial (10/2010-9/2013) of an EPC telehealth intervention for CGs (n = 123) initiated at the time of care recipients' advanced cancer diagnosis (early group) or 12 weeks later (delayed group) in a rural comprehensive cancer center, affiliated clinics, and a Veterans Administration medical center. The ENABLE [Educate, Nurture, Advise, Before Life Ends] CG intervention consisted of three weekly sessions, monthly follow-up, and a bereavement call. CGs completed the Center for Epidemiological Study-Depression (CES-D) scale and the Prigerson Inventory of Complicated Grief-Short Form (PG13) 8-12 weeks after care recipients' deaths. Crude and covariate-adjusted between group differences were estimated and tested using general linear models. RESULTS: For care recipients who died (n = 70), 44 CGs (early: n = 19; delayed: n = 25) completed after-death questionnaires. Mean depressive symptom scores (CES-D) for the early group was 14.6 (SD = 10.7) and for the delayed group was 17.6 (SD = 11.8). Mean complicated grief scores (PG13) for the early group was 22.7 (SD = 4.9) and for the delayed group was 24.9 (SD = 6.9). Adjusted between-group differences were not statistically significant (CES-D: d = 0.07, P = 0.88; PG13: d = -0.21, P = 0.51). CONCLUSION: CGs' depressive symptom and complicated grief scores 8-12 weeks after care recipients' deaths were not statistically different based on the timing of EPC support. The impact of timing of CG EPC interventions on CGs bereavement outcomes requires further investigation. PMID- 27265815 TI - Symptom Burden and End-of-Life Treatment Preferences in the Very Old. AB - CONTEXT: End-of-life (EOL) treatment preferences among the very old (age 85+) may differ from preferences in younger aged populations because of high levels of symptom burden and disability and high risk of mortality. It is unclear if symptom burden or level of disability is more important for such preferences. OBJECTIVES: To investigate whether distress from daily symptom burden was an independent correlate of EOL treatment preferences over two years of follow-up in people with median age 86 (participants) and 88 (reported by proxies) at baseline. METHODS: The End of Life in Very Old Age is an ancillary study to the Health, Aging and Body Composition study. At baseline in Year 15 of Health, Aging and Body Composition, 1038 participants and 189 proxies reported levels of symptom distress every quarter, as well as 0-8 EOL treatment preferences elicited once each year. RESULTS: At baseline, the mean (SD) count of EOL treatment preferences was 4.2 (2.1) in participants, and 2.9 (2.3) in proxies. EOL treatment preference was not associated with symptom distress. By contrast, black race, male gender, and reported ease walking a quarter mile were independently associated with more aggressive EOL treatment preferences. CONCLUSION: Preferences for more aggressive EOL treatment were not related to daily symptom distress but were significantly more likely to be endorsed among those with better mobility, suggesting that disability is an independent predictor of EOL treatment preferences in the very old. PMID- 27265817 TI - Trend in and Correlates of Undergoing Radiotherapy in Taiwanese Cancer Patients' Last Month of Life. AB - CONTEXT: A significant proportion of cancer patients at end of life (EOL) undergo radiotherapy, but this evidence is not from nationwide population-based studies. OBJECTIVES: The aims of this population-based study were to investigate the trend in undergoing radiotherapy among Taiwanese cancer patients' last month of life (EOL radiotherapy) in 2001-2010 and to identify factors associated with EOL radiotherapy. METHODS: This was a population-based retrospective cohort study analyzing data from Taiwan's national death registry, cancer registry, and National Health Insurance claims for EOL radiotherapy using multilevel generalized linear mixed modeling. Participants were Taiwanese cancer patients (N = 339,546) who died in 2001-2010. RESULTS: Overall, 8.59% (7.97%-9.85%) of patients underwent EOL radiotherapy with a decreasing trend over time. Correlates of EOL radiotherapy included male gender, younger age, residing in less urbanized areas, diagnosis of lung cancer, metastatic disease, death within two years of diagnosis, and without comorbidities. Cancer patients were more likely to undergo EOL radiotherapy if they received primary care from medical oncologists and pediatricians, in a nonprofit, teaching hospital with a larger case volume of terminally ill cancer patients, and greater EOL care intensity. CONCLUSION: Approximately one-tenth of Taiwanese cancer patients underwent EOL radiotherapy with a decreasing trend over time. Undergoing EOL radiotherapy was associated with demographics, disease characteristics, physician specialty, and primary hospital's characteristics and EOL care practice patterns. Clinical and financial interventions should target hospitals/physicians that tend to aggressively treat at-risk cancer patients at EOL to carefully evaluate the appropriateness and effectiveness of using EOL radiotherapy. PMID- 27265816 TI - Nordic Walking as an Exercise Intervention to Reduce Pain in Women With Aromatase Inhibitor-Associated Arthralgia: A Feasibility Study. AB - CONTEXT: Women taking aromatase inhibitors as treatment for breast cancer commonly experience joint pain and stiffness (aromatase inhibitor-associated arthralgia [AIAA]), which can cause problems with adherence. There is evidence that exercise might be helpful, and Nordic walking could reduce joint pain compared to normal walking. OBJECTIVES: To determine the feasibility of a trial of Nordic walking as an exercise intervention for women with AIAA. METHODS: A feasibility study was carried out in a sample of women with AIAA using a randomized control design. Women were randomized to exercise (six-week supervised group Nordic walking training once per week with an increasing independent element, followed by six weeks 4 * 30 minutes/week independent Nordic walking); or enhanced usual care. Data were collected on recruitment, retention, exercise adherence, safety, and acceptability. The Brief Pain Inventory, GP Physical Activity Questionnaire, and biopsychosocial measures were completed at baseline, six and 12 weeks. RESULTS: Forty of 159 eligible women were recruited and attrition was 10%. There was no increased lymphedema and no long-term or serious injury. Adherence was >90% for weekly supervised group Nordic walking, and during independent Nordic walking, >80% women managed one to two Nordic walking sessions per week. From baseline to study end point, overall activity levels increased and pain reduced in both the intervention and control groups. CONCLUSION: Our findings indicate that women with AIAA are prepared to take up Nordic walking, complete a six-week supervised course and maintain increased activity levels over a 12-week period with no adverse effects. PMID- 27265818 TI - Thromboprophylaxis adherence to the ninth edition of American college of chest physicians antithrombotic guidelines in a tertiary care centre: a cross-sectional study. AB - RATIONALE: Venous thromboembolic disease is a source of significant morbidity in hospitalized patients. The American College of Chest Physicians published the ninth edition of antithrombotic therapy and prevention guidelines (AT9) in 2012, addressing thromboprophylaxis in hospitalized patients. A notable difference from previous guidelines was utilization of risk assessment models for thrombosis and bleeding to classify patients into risk categories. AIM: This study's objective was to evaluate thromboprophylaxis adherence to AT9 guidelines in a population of patients at the Centre integre universitaire de sante et de service sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke. METHOD: A cross sectional study at the Centre integre universitaire de sante et de service sociaux de l'Estrie - Centre hospitalier universitaire de Sherbrooke was performed between June and December 2012. Patients' risk factors for thrombosis and bleeding, and thromboprophylaxis use were documented. The Padua and Caprini models were used to determine thrombotic risk, and the International Medical Prevention Registry on Venous Thromboembolism bleeding risk score was used for bleeding risk. RESULTS: A total of 290 patients were included for analysis. Overall, 200 patients (70%) received some form of thromboprophylaxis. However, according to AT9 guidelines, only 162 patients (55.9%) received recommended prophylaxis, 91 (31.4%) had overuse of prophylaxis and 37 (12.7%) had underuse of prophylaxis. Appropriate prophylaxis use was higher in surgical (61.8%) than in medical (46.7%) patients. CONCLUSIONS: There was a high rate of inappropriate thromboembolic prophylaxis in our centre according to AT9 guidelines, mostly from overuse of prophylaxis. Utilization of risk assessment models in AT9 guidelines adds to the complexity of physician's decisions to prescribe thromboprophylaxis and needs further validation. PMID- 27265819 TI - To branch or to expand? AB - Oscillating protein signals control the branching and expansion of blood vessels. PMID- 27265820 TI - Mutation (G275E) of the nicotinic acetylcholine receptor alpha6 subunit is associated with high levels of resistance to spinosyns in Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae). AB - The tomato leafminer, Tuta absoluta, now a major pest of tomato crops worldwide, is primarily controlled using chemical insecticides. Recently, high levels of resistance to the insecticide spinosad have been described in T. absoluta populations in Brazil. Selection of a resistant field-collected strain led to very high levels of resistance to spinosad and cross-resistance to spinetoram, but not to other insecticides that target the nicotinic acetylcholine receptor (nAChR). In this study the mechanisms underlying resistance to spinosad were investigated using toxicological, biochemical and molecular approaches. Inhibition of metabolic enzymes using synergists and biochemical assessment of detoxification enzyme activity provided little evidence of metabolic resistance in the selected strain. Cloning and sequencing of the nAChR alpha6 subunit from T. absoluta, the spinosad target-site, from susceptible and spinosad-resistant strains were done to investigate the role of a target-site mechanism in resistance. A single nucleotide change was identified in exon 9 of the alpha6 subunit of the resistant strain, resulting in the replacement of the glycine (G) residue at position 275 observed in susceptible T. absoluta strains with a glutamic acid (E). A high-throughput DNA-based diagnostic assay was developed and used to assess the prevalence of the G275E mutation in 17 field populations collected from different geographical regions of Brazil. The resistant allele was found at low frequency, and in the heterozygous form, in seven of these populations but at much higher frequency and in the homozygous form in a population collected in the Iraquara municipality. The frequency of the mutation was significantly correlated with the mortality of these populations in discriminating dose bioassays. In summary our results provide evidence that the G275E mutation is an important mechanism of resistance to spinosyns in T. absoluta, and may be used as a marker for resistance monitoring in field populations. PMID- 27265821 TI - Imidacloprid induced histomorphological changes and expression of TLR-4 and TNFalpha in lung. AB - The imidacloprid is used worldwide as a pesticide and has been linked with endocrine disturbances and reduced pulmonary function. However, effects of imidacloprid alone or in combination with microbial molecules on lungs are not fully understood. Because the pulmonary effects of interactions of endotoxins with imidacloprid are unknown, we designed a study to investigate that in a mouse model. Mice (N=14) were given imidacloprid orally @ 1/20(th) of LD50 dissolved in corn oil for 30days. After the treatments, six animals from each group were challenged with E. coli lipopolysaccharide (LPS) @ 80MUg/animal via intranasal route and remaining animals were challenged with normal saline solution @ 80MUl/animal via same route. Imidacloprid in combination with LPS led to significant increase in total cell and neutrophil counts in BAL and peripheral blood. Semi-quantitative histopathology revealed lung injury in imidacloprid treatment group and injury was more marked in animal receiving both imidacloprid and LPS. There was no change (p<0.05) in the expression of TLR-4 and TNF-alpha both at mRNA and protein levels following exposure to imidacloprid alone or in combination with LPS. The data show that imidacloprid alone or in combination with LPS resulted changes in lung morphology without altering the expression of TLR-4 and TNF-alpha. Furthermore, pre-treatment with imidacloprid didn't affect response to LPS. PMID- 27265822 TI - Development of an antibody-based diagnostic method for the identification of Bemisia tabaci biotype B. AB - The whitefly Bemisia tabaci is a very destructive pest. B. tabaci is composed of various morphologically undistinguishable biotypes, among which biotypes B and Q, in particular, draw attention because of their wide distribution in Korea and differential potentials for insecticide resistance development. To develop a biotype-specific protein marker that can readily distinguishes biotypes B from other biotypes in the field, we established an ELISA protocol based on carboxylesterase 2 (COE2), which is more abundantly expressed in biotypes B compared with Q. Recombinant COE2 was expressed, purified and used for antibody construction. Polyclonal antibodies specific to B. tabaci COE2 [anti-COE2 pAb and deglycosylated anti-COE2 pAb (DG anti-COE2 pAb)] revealed a 3-9-fold higher reactivity to biotype B COE2 than biotype Q COE2 by Western blot and ELISA analyses. DG anti-COE2 pAb exhibited low non-specific activity, demonstrating its compatibility in diagnosing biotypes. Western blot and ELISA analyses determined that one of the 11 field populations examined was biotype B and the others were biotype Q, suggesting the saturation of biotype Q in Korea. DG anti-COE2 pAb discriminates B. tabaci biotypes B and Q with high specificity and accuracy and could be useful for the development of a B. tabaci biotype diagnosis kit for on site field applications. PMID- 27265823 TI - Identification of a carboxylesterase associated with resistance to naled in Bactrocera dorsalis (Hendel). AB - Compared to other organophosphate-resistant and -susceptible (S) lines of Bactrocera dorsalis, the carboxylesterase (CBE) BdE5 in the naled-resistant (nal r) line has been found to possess remarkable quantitative elevation. Our study attempts to identify the role of BdE5 in naled resistance, and we discovered several points of interest. Firstly, activity staining on native PAGE revealed that the percentage of flies with intensive BdE5 bands in the nal-r line was substantially higher than in the S line, indicating that the BdE5 band correlates with naled susceptibility. Secondly, in vitro and in vivo inhibition assays showed that BdE5 was inhibited by naled in both lines; under diagnostic doses of naled, the overall extent of inhibition on CBEs was much greater in the S line than in the nal-r line. Thirdly, NanoLC-nanoESi-MS/MS analysis used the NCBI database to identify and annotate BdE5 as an esterase FE4-like (XP_011200445.1) in B. dorsalis. Fourthly, rapid amplification of cDNA ends was used to obtain the 2012-bp full-length BdE5 cDNA, which contained an open reading frame of 1770bp and encoded a putative protein of 590 amino acid residues. Phylogenetic analysis revealed that BdE5 is a secreted beta-esterase (E clade) closely related to CG6414 (NP_570089), a CBE in Drosophila melanogaster. Finally, our relative quantification real-time PCR data showed a significant elevation in transcript levels of the BdE5 gene in nal-r line. Our results confirmed that BdE5 is correlated with naled resistance and provides further understanding about the identification and molecular characteristics of BdE5 in B. dorsalis. PMID- 27265824 TI - The RING for gypsy moth control: Topical application of fragment of its nuclear polyhedrosis virus anti-apoptosis gene as insecticide. AB - Numerous studies suggest a cellular origin for the Lymantria dispar multicapsid nuclear polyhedrosis virus (LdMNPV) anti-apoptosis genes IAPs, thus opening a possibility to use the fragments of these genes for modulation of host metabolism. We report here the strong insecticidal and metabolic effect of single stranded antisense DNA fragment from RING (really interesting new gene) domain of gypsy moth LdMNPV IAP-3 gene: specifically, on reduction of biomass (by 35%) and survival of L. dispar caterpillars. The treatment with this DNA fragment leads to a significantly higher mortality rates of female insects (1.7 fold) accompanied with the signs of apoptosis. Additionally, we show increased expression of host IAP-1, caspase-4 and gelsolin genes in eggs laid by survived females treated with RING DNA fragment accompanied with calcium and magnesium imbalance, indicating that the strong stress reactions and metabolic effects are not confined to treated insects but likely led to apoptosis in eggs too. The proposed new approach for insect pest management, which can be considered as advancement of "microbial pesticides", is based on the application of the specific virus DNA, exploiting the knowledge about virus-pest interactions and putting it to the benefit of mankind. PMID- 27265825 TI - 4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4' dichlorodiphenyldichloroethylene (DDE) promote adipogenesis in 3T3-L1 adipocyte cell culture. AB - 4,4'-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4'-dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 adipocytes. Treatment of DDT or DDE resulted in increased lipid accumulation accompanied by increased expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha), peroxisome-proliferator activated receptor-gamma (PPARgamma), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipose triglyceride lipase, and leptin. Moreover, treatment of DDT or DDE increased protein levels of C/EBPalpha, PPARgamma, AMP-activated protein kinase-alpha (AMPKalpha), and ACC, while significant decrease of phosphorylated forms of AMPKalpha and ACC were observed. These finding suggest that increased lipid accumulation caused by DDT and DDE may mediate AMPKalpha pathway in 3T3-L1 adipocytes. PMID- 27265826 TI - Insecticidal potential of an endophytic Cladosporium velox against Spodoptera litura mediated through inhibition of alpha glycosidases. AB - Alpha glucosidase inhibitory activity was exhibited by partially purified fractions obtained from an endophytic Cladosporium velox, isolated from Tinospora cordifolia. Taking into account the increasing importance of digestive enzyme inhibitors as insecticidal agents, the entomopathogenic potential of the fractions obtained was evaluated against Spodoptera litura (Fab.), a polyphagous pest. Considerable mortality was obtained when the larvae were fed on diet supplemented with the partially purified extract. All the concentrations of the extract significantly prolonged the overall developmental period of S. litura. At higher concentrations, the extract influenced the longevity of females as well as their reproductive potential. Phytochemical analysis revealed the presence of phenolic compounds in the active fraction. The phenolic compound responsible for the bioactivities was purified and identified to be chlorogenic acid using HPLC and MS analysis. The content of chlorogenic acid in the extract was quantified to be 250MUg/ml. The purified compound also demonstrated inhibition of alpha glycosidases in vivo. The present study indicates that the endophyte imparted resistance to the insects in the plants could be mediated through chlorogenic acid targeting the alpha glycosidases present in the gut of the insect. The isolate obtained can be exploited for the production of chlorogenic acid, which has the potential to be exploited as a biocontrol agent against S. litura. PMID- 27265827 TI - Effects of tea saponin on growth and development, nutritional indicators, and hormone titers in diamondback moths feeding on different host plant species. AB - The diamondback moth (DBM) is an important worldwide pest. This insect has been studied for several decades; however, its control remains problematic. Numerous chemical insecticides have become ineffective and chemical residues constitute an important problem. In the present study, we determined the mortality of 3rd instar DBM larvae feeding on three different host plant species and exposed to various concentrations of tea saponin (TS). In addition, we evaluated growth and development parameters, nutritional indicators, and juvenile hormone (JH) and molting hormone (MH) titers in 2nd instar larvae exposed to LC20 and LC50 doses of TS. We found that treatment of DBM larvae with LC20 and LC50 doses of TS led to lower growth rates, decreased feed consumption, reduced frass production, lower pupal weights, reduced percentage pupation, slower adult emergence percentages, and diminished fecundity, but prolonged durations of the larval and pupal periods. The efficiency of conversion of ingested and digested food increased, but the approximate digestibility did not differ significantly between treatments and controls. JH and MH titers were higher after TS treatment; these increases varied according to the host species and TS concentration. Our results indicate that TS represents a potential new alternative insecticide based on its natural origin, low cost, and minimum environmental impact. PMID- 27265828 TI - Acarine attractants: Chemoreception, bioassay, chemistry and control. AB - The Acari are of significant economic importance in crop production and human and animal health. Acaricides are essential for the control of these pests, but at the same time, the number of available pesticides is limited, especially for applications in animal production. The Acari consist of two major groups, the mites that demonstrate a wide variety of life strategies, i.e., herbivory, predation and ectoparasitism, and ticks which have evolved obligatory hematophagy. The major sites of chemoreception in the acarines are the chelicerae, palps and tarsi on the forelegs. A unifying name, the "foretarsal sensory organ" (FSO), is proposed for the first time in this review for the sensory site on the forelegs of all acarines. The FSO has multiple sensory functions including olfaction, gustation, and heat detection. Preliminary transcriptomic data in ticks suggest that chemoreception in the FSO is achieved by a different mechanism from insects. There are a variety of laboratory and field bioassay methods that have been developed for the identification and characterization of attractants but minimal techniques for electrophysiology studies. Over the past three to four decades, significant progress has been made in the chemistry and analysis of function for acarine attractants in mites and ticks. In mites, attractants include aggregation, immature female, female sex and alarm pheromones; in ticks, the attraction-aggregation-attachment, assembly and sex pheromones; in mites and ticks host kairomones and plant allomones; and in mites, fungal allomones. There are still large gaps in our knowledge of chemical communication in the acarines compared to insects, especially relative to acarine pheromones, and more so for mites than ticks. However, the use of lure-and-kill and lure-enhanced biocontrol strategies has been investigated for tick and mite control, respectively, with significant environmental advantages which warrant further study. PMID- 27265829 TI - Identification of an alkaline phosphatase as a putative Cry1Ac binding protein in Ostrinia furnacalis (Guenee). AB - Asian corn borer (ACB), Ostrinia furnacalis, is an important insect pest of maize susceptible to different Cry1A toxins. Based on amino acid sequence alignment of ALP sequences from lepidopteran larvae an alp gene was cloned from ACB, named ofalp. Pull dawn assays using biotinylated Cry1Ac and brush border membrane vesicles isolated from second instar ACB larvae showed that four proteins of 50, 65, 68 and 70kDa precipitated with the Cry1Ac. The 65kDa band cross-reacted with the anti-OfALP monoclonal antibody. GalNac was able to release the binding of Cry1Ac to the 65kDa OfALP in pull down assays. A 37kDa fragment from residues D173 to D473 of OfALP was cloned and expressed in Escherichia coli cells. We show that this ALP-fragment was able to bind Cry1Ac in ligand blot analysis. Our data also indicate that different ALP isoforms or variants may be also Cry1Ac binding proteins since more ALP enzymatic activity was pull down with Cry1Ac than with anti-OfALP antibody. We also analyzed the expression levels of ALP throughout the larval development by qPCR and ALP enzymatic activity. Our data indicated that ALP expression in ACB was observed preferentially in young instar larvae. Finally, we show that resistance in O. furnacalis ACB-AcR strain resistant to Cry1Ac did not correlate with changes in expression of this ALP protein since it shows similar gene expression of ofalp than the susceptible insect strain. Identification of Cry1Ac receptors will help to understand mechanism of action of Cry1Ac in O. furnacalis and to understand mechanism of Cry toxin resistance. Our data indicate that at least one ALP protein is involved in the binding interaction with Cry1Ac in O. furnacalis. PMID- 27265830 TI - Characteristics of carboxylesterase genes and their expression-level between acaricide-susceptible and resistant Tetranychus cinnabarinus (Boisduval). AB - Carboxylesterases (CarEs) play important roles in metabolism and detoxification of dietary and environmental xenobiotics in insects and mites. On the basis of the Tetranychuscinnabarinus transcriptome dataset, 23 CarE genes (6 genes are full sequence and 17 genes are partial sequence) were identified. Synergist bioassay showed that CarEs were involved in acaricide detoxification and resistance in fenpropathrin- (FeR) and cyflumetofen-resistant (CyR) strains. In order to further reveal the relationship between CarE gene's expression and acaricide-resistance in T. cinnabarinus, we profiled their expression in susceptible (SS) and resistant strains (FeR, and CyR). There were 8 and 4 over expressed carboxylesterase genes in FeR and CyR, respectively, from which the over-expressions were detected at mRNA level, but not DNA level. Pesticide induction experiment elucidated that 4 of 8 and 2 of 4 up-regulated genes were inducible with significance in FeR and CyR strains, respectively, but they could not be induced in SS strain, which indicated that these genes became more enhanced and effective to withstand the pesticides' stress in resistant T. cinnabarinus. Most expression-changed and all inducible genes possess the Abhydrolase_3 motif, which is a catalytic domain for hydrolyzing. As a whole, these findings in current study provide clues for further elucidating the function and regulation mechanism of these carboxylesterase genes in T. cinnabarinus' resistance formation. PMID- 27265831 TI - White Matter Hyperintensities on Brain Magnetic Resonance Imaging in People with Epilepsy: A Hospital-Based Study. AB - AIMS: We aim to explore whether people with epilepsy have increased white matter hyperintensities (WMHs). METHODS: Eligible patients were categorized into newly diagnosed epilepsy (NE) and chronic epilepsy (CE); the latter were subdivided to those treated with enzyme-inducing antiepileptic drugs (EIAEDs) with or without non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those with NEIAEDs only. WMHs were measured using age-related white matter changes (ARWMC) scale and compared between patients and healthy control group. Higher scores indicate greater WMH changes. The strengths of associations were estimated as incidence rate ratios (IRRs) with 95% confidence interval (CI). RESULTS: A total of 217 patients were included in the analysis, of whom 67 had NE, 45 had CE treated with NEIAEDs, and 105 had CE treated with EIAEDs. Age was positively associated with ARWMC score (IRR per year, 1.03; 95%CI, 1.03-1.04, P < 0.001). Compared with the healthy control group (n = 23), all patient groups had higher ARWMC score (P < 0.05). The difference was greatest in patients receiving EIAEDs (IRR, 2.13; 95%CI, 1.22-3.70, P = 0.007). CONCLUSIONS: WMHs tended to be observed in people with epilepsy, especially in those treated with EIAEDs. People with epilepsy with white matter changes should be evaluated for stroke risk, particularly if they are receiving EIAEDs. PMID- 27265832 TI - D-lactic acidosis: A rare cause of metabolic acidosis. PMID- 27265834 TI - A Robust Epoxy Resins @ Stearic Acid-Mg(OH)2 Micronanosheet Superhydrophobic Omnipotent Protective Coating for Real-Life Applications. AB - Superhydrophobic coating has extremely high application value and practicability. However, some difficult problems such as weak mechanical strength, the need for expensive toxic reagents, and a complex preparation process are all hard to avoid, and these problems have impeded the superhydrophobic coating's real-life application for a long time. Here, we demonstrate one kind of omnipotent epoxy resins @ stearic acid-Mg(OH)2 superhydrophobic coating via a simple antideposition route and one-step superhydrophobization process. The whole preparation process is facile, and expensive toxic reagents needed. This omnipotent coating can be applied on any solid substrate with great waterproof ability, excellent mechanical stability, and chemical durability, which can be stored in a realistic environment for more than 1 month. More significantly, this superhydrophobic coating also has four protective abilities, antifouling, anticorrosion, anti-icing, and flame-retardancy, to cope with a variety of possible extreme natural environments. Therefore, this omnipotent epoxy resins @ stearic acid-Mg(OH)2 superhydrophobic coating not only satisfies real-life need but also has great application potential in many respects. PMID- 27265833 TI - A C-terminally truncated mouse Best3 splice variant targets and alters the ion balance in lysosome-endosome hybrids and the endoplasmic reticulum. AB - The Bestrophin family has been characterized as Cl(-) channels in mammals and Na(+) channels in bacteria, but their exact physiological roles remian unknown. In this study, a natural C-terminally truncated variant of mouse Bestrophin 3 (Best3V2) expression in myoblasts and muscles is demonstrated. Unlike full-length Best3, Best3V2 targets the two important intracellular Ca stores: the lysosome and the ER. Heterologous overexpression leads to lysosome swelling and renders it less acidic. Best3V2 overexpression also results in compromised Ca(2+) release from the ER. Knocking down endogenous Best3 expression in myoblasts makes these cells more excitable in response to Ca(2+) mobilizing reagents, such as caffeine. We propose that Best3V2 in myoblasts may work as a tuner to control Ca(2+) release from intracellular Ca(2+) stores. PMID- 27265835 TI - Pediatric Malignant Bone Tumors: A Review and Update on Current Challenges, and Emerging Drug Targets. AB - Osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT) are the most common malignant bone tumors in children and adolescents. While significant improvements in survival have been seen in other pediatric malignancies the treatment and prognosis for pediatric bone tumors has remained unchanged for the past 3 decades. This review and update of pediatric malignant bone tumors will provide a general overview of osteosarcoma and the Ewing sarcoma family of tumors, discuss bone tumor genomics, current challenges, and emerging drug targets. PMID- 27265836 TI - Combination of Helicobacter pylori Antibody and Serum Pepsinogen as a Good Predictive Tool of Gastric Cancer Incidence: 20-Year Prospective Data From the Hisayama Study. AB - BACKGROUND: There is little information regarding whether the combination of Helicobacter pylori (H. pylori) antibody and serum pepsinogen (sPG), which is a marker of the degree of atrophic gastritis, has a discriminatory ability for detecting incident gastric cancer. We examined this issue in a long-term prospective cohort study of a Japanese population. METHODS: A total of 2446 Japanese community-dwelling individuals aged >=40 years were stratified into four groups according to baseline H. pylori serological status and sPG: Group A (H. pylori[-], sPG[-]), Group B (H. pylori[+], sPG[-]), Group C (H. pylori[+], sPG[+]), and Group D (H. pylori[-], sPG[+]), and participants were followed up prospectively for 20 years. RESULTS: During the follow-up, 123 subjects developed gastric cancer. Compared with that in Group A, the cumulative incidence of gastric cancer was significantly increased in Groups B, C, and D, whereas no significant difference was found between Groups C and D. The multivariable adjusted risk of gastric cancer was significantly increased in Group B (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.62-10.28) and in Groups C and D combined (HR 11.1; 95% CI, 4.45-27.46). When the multivariable model with H. pylori antibody was changed into that with the combination of H. pylori antibody and sPG, the C statistics for developing gastric cancer increased significantly (0.773 vs 0.732, P = 0.005), and the continuous net reclassification improvement value was 0.591 (P < 0.001). CONCLUSIONS: Our findings suggest that the combination of H. pylori antibody and sPG is a useful tool for predicting the development of gastric cancer. PMID- 27265837 TI - The influence of baseline characteristics and disease stage on health-related quality of life in multiple myeloma: findings from six randomized controlled trials. AB - This descriptive, cross-sectional analysis evaluated the impact of baseline characteristics on health-related quality of life (HR-QoL) at different stages of multiple myeloma (MM). The bortezomib clinical-trial programme evaluated HR-QoL early and consistently, producing a large multi-study dataset. Baseline data, captured using the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-C30), were pooled from six bortezomib randomized trials conducted in different disease-stage categories: 'New' (previously untreated; n = 753), 'Early' (1-3 prior therapies; n = 1569) and 'Late' (>=4 prior therapies; n = 239) disease. Mean EORTC global health scores were similar across the three stages. Unexpectedly, emotional, physical and role functioning were higher in the later stages, indicating better perceived health. Symptom scores, including pain, were largely similar or lower in the later versus earlier stages, signifying a lower symptom burden/better symptom control with more advanced disease. Notable variation in HR-QoL was observed by age and clinical parameters within and across stages. Multivariate modelling indicated that opioid use and performance status were key factors driving overall HR-QoL across stages. Using an age-restricted analysis, transplant eligibility had little impact on HR-QoL in New disease patients. Thus, changes in HR-QoL over the treatment course of MM are complex and impacted by baseline factors. A prospective observational international inception cohort study that captures key clinical, HR-QoL and demographic characteristics, along with safety and supportive care information, is needed. PMID- 27265838 TI - Polyploidy in a 'living fossil' Ginkgo biloba. PMID- 27265839 TI - Introduction to the 2016 Consensus Document on European Brain Research. PMID- 27265841 TI - US Black college women's sexual health in hookup culture: intersections of race and gender. AB - Approximately 60-80% of college students in the USA report a hookup experience in the form of a casual sexual encounter between individuals without the expectation of a dating or romantic relationship. Given the potential health risk posed by these sexual encounters, the need exists to critically examine this cultural phenomenon on college campuses. Yet, the existing hookup literature is overwhelming White and often exclusive of historically marginalised populations such as Black women. Accordingly, this paper examines the role of the intersecting identities of race and gender and other social factors that influence the sexual health and wellbeing of Black women on US college campuses. Specifically, we explore issues related to the gender ratio disparities present on college campuses, relationship power imbalances, inconsistent condom use and low sexual-risk perception. Moving forward, hookup research needs to utilise an intersectional approach; we offer specific suggestions for the important inclusion of Black women in the broader hookup discourse and future research. PMID- 27265840 TI - A metabolomics cell-based approach for anticipating and investigating drug induced liver injury. AB - In preclinical stages of drug development, anticipating potential adverse drug effects such as toxicity is an important issue for both saving resources and preventing public health risks. Current in vitro cytotoxicity tests are restricted by their predictive potential and their ability to provide mechanistic information. This study aimed to develop a metabolomic mass spectrometry-based approach for the detection and classification of drug-induced hepatotoxicity. To this end, the metabolite profiles of human derived hepatic cells (i.e., HepG2) exposed to different well-known hepatotoxic compounds acting through different mechanisms (i.e., oxidative stress, steatosis, phospholipidosis, and controls) were compared by multivariate data analysis, thus allowing us to decipher both common and mechanism-specific altered biochemical pathways. Briefly, oxidative stress damage markers were found in the three mechanisms, mainly showing altered levels of metabolites associated with glutathione and gamma-glutamyl cycle. Phospholipidosis was characterized by a decreased lysophospholipids to phospholipids ratio, suggestive of phospholipid degradation inhibition. Whereas, steatosis led to impaired fatty acids beta-oxidation and a subsequent increase in triacylglycerides synthesis. The characteristic metabolomic profiles were used to develop a predictive model aimed not only to discriminate between non-toxic and hepatotoxic drugs, but also to propose potential drug toxicity mechanism(s). PMID- 27265842 TI - CRISPR/Cas9 genome editing throws descriptive 3-D genome folding studies for a loop. AB - CRISPR/Cas9 genome editing studies have recently shed new light into the causal link between the linear DNA sequence and 3-D chromatin architecture. Here we describe current models for the folding of genomes into a nested hierarchy of higher-order structures and discuss new insights into the organizing principles governing genome folding at each length scale. WIREs Syst Biol Med 2016, 8:286 299. doi: 10.1002/wsbm.1338 For further resources related to this article, please visit the WIREs website. PMID- 27265843 TI - Controversy in Purchasing Prescription Drugs Online in China. AB - China's government is considering legalization of online prescription drugs to increase the pharmaceutical market and enhance access to necessary medicines. However, challenges such as a shortage of licensed pharmacists and drug quality issues have raised concerns and delayed consensus on the proposal. China's government must address the most pressing issues so it can render a decision on online prescription sales. PMID- 27265845 TI - The Association of CYP1A1 Gene With Cervical Cancer and Additional SNP-SNP Interaction in Chinese Women. AB - AIMS: The aim of this study was to investigate the association between CYP1A1 gene polymorphism and cervical cancer risk, and the impact of SNP-SNP interaction on cervical cancer risk in Chinese women. METHODS: A total of 728 females with a mean age of 60.1 +/- 14.5 years old were selected, including 360 cervical cancer patients and 368 normal controls. Logistic regression was performed to investigate association between single-nucleotide polymorphisms (SNP) and cervical cancer risk. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the SNP-SNP interaction. RESULTS: Logistic analysis showed a significant association between rs4646903 and increased cervical cancer risk. The carriers of homozygous mutant of rs4646903 polymorphism revealed increased cervical cancer risk than those with wild-type homozygotes, OR (95%CI) were 1.45 (1.20-1.95). There was a significant two-locus model (P = 0.0107) involving rs4646903 and rs1048943, indicating a potential SNP-SNP interaction between rs4646903 and rs1048943. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. Subjects with TC or CC of rs4646903 and AG or GG of rs1048943 genotype have the highest cervical cancer risk, compared to subjects with TT of rs4646903 and AA of rs1048943 genotype, OR (95%CI) was 2.03 (1.42-2.89). CONCLUSIONS: rs4646903 minor alleles and interaction between rs4646903 and rs1048943 were associated with increased cervical cancer risk. PMID- 27265844 TI - Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy. AB - AIMS: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole-body dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (beta) represent the placebo-controlled mean effect of intervention. RESULTS: LBM (beta = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (beta = -1.3 kg, p = 0.009), fat mass trunk (beta = -0.7 kg, p = 0.043), fat mass legs (beta = -0.7 kg, p = 0.025), fat mass arms (beta = -0.3 kg, p = 0.001), and HDL cholesterol (beta = 0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin stimulated rates of EGP, lipid- and glucose-oxidation were unaltered after TRT. CONCLUSION: TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged. PMID- 27265846 TI - Pelvic floor muscle reflex activity during coughing - an exploratory and reliability study. AB - OBJECTIVES: Activities that provoke stress urinary incontinence (SUI) rapidly increase the intra-abdominal pressure and the impact loading on the pelvic floor muscles (PFMs). Coughing can cause urinary leakage and is often used to test SUI. However, PFM characteristics during coughing, including their reliability, have not been investigated. Here, we used electromyography (EMG) to describe PFM pre activity and reflexivity during coughing and examined the reliability of the measurements. METHODS: This was an exploratory and reliability study including 11 young healthy women to characterize EMG reflex activity in PFMs during coughing. We describe 6 variables, averaged over 3 coughs per subject, and tested their reliability (intraclass correlation coefficient 3,1 [ICC(3,1)] and ICC(3,k), related standard error of measurement (SEM) and minimal difference [MD]). The variables represented the mean EMG activity for PFMs during 30-ms time intervals of pre-activity (initial time point of coughing [T0] and minus 30ms) and reflex activity (T0-30, 30-60, 60-90, 90-120 and 120-150ms after T0) of stretch-reflex latency responses. RESULTS: The mean %EMG (normalized to maximal voluntary PFM contraction) for EMG variables was 35.1 to 52.2 and was significantly higher during coughing than for PFM activity at rest (mean 24.9+/-3.7%EMG; P<0.05). ICC(3,k) ranged from 0.67 to 0.91 (SEM 6.1-13.3%EMG and MD 16.7-36.8%EMG) and was higher than ICC(3,1) (range 0.40-0.77; SEM 9.0-18.0%EMG, MD 24.9-50.0%EMG). CONCLUSIONS: PFM activity during reflex latency response time intervals during coughing was significantly higher than at rest, which suggests PFM pre-activity and reflex activity during coughing. Although we standardized coughing, EMG variables for PFM activity showed poor reliability [good to excellent ICC(3,k) and fair to excellent ICC(3,1) but high SEM and MD]. Therefore, coughing is expected to be heterogeneous, with low reliability, in clinical test situations. Potential crosstalk from other muscles involved in coughing could limit the interpretation of our results. PMID- 27265847 TI - Infant and young child feeding practices and stunting in two highland provinces in Ecuador. AB - The first two years of life are critical for growth and development. Little is known about infant and young child feeding (IYCF) practices in the Ecuadorian highlands and how they contribute to stunting. With the objective of understanding nutritional status and the influencing factors to design an intervention, we assessed the nutritional status of 293 infants and children between 0 and 24 months of age, living in 14 communities in the provinces of Tungurahua and Chimborazo using a cross-sectional study design. We used the WHO IYCF indicators to assess feeding practices; estimated dietary intake with 24-h recalls; and identified nutritious local foods by food frequency questionnaires. Multiple regression modelling was performed to identify correlates of nutritional status. Stunting was found in 56.2% of children. Mean protein, vitamin A and vitamin C intakes were above recommendations for all ages. Only infants 6.0 to 8.9 months of age and non-breastfed children 12-23.9 months of age consumed energy intakes below recommendations. Younger age groups had below recommended intakes for iron and calcium. While mean complementary food densities met recommendations for protein, vitamin A, vitamin C and energy, those for zinc, iron and calcium were lower than recommended. Older age, respiratory infections and being male were predictors of lower HAZ, whereas early initiation of breastfeeding, higher socioeconomic status, consumption of iron-rich foods and higher dietary protein density were protective. Interventions that promote and support optimal breastfeeding practices and enable increased consumption of nutritious local foods have potential to contribute to reducing stunting in this vulnerable population. (c) 2016 John Wiley & Sons Ltd. PMID- 27265848 TI - Interaction between Prion Protein's Copper-Bound Octarepeat Domain and a Charged C-Terminal Pocket Suggests a Mechanism for N-Terminal Regulation. AB - Copper plays a critical role in prion protein (PrP) physiology. Cu(2+) binds with high affinity to the PrP N-terminal octarepeat (OR) domain, and intracellular copper promotes PrP expression. The molecular details of copper coordination within the OR are now well characterized. Here we examine how Cu(2+) influences the interaction between the PrP N-terminal domain and the C-terminal globular domain. Using nuclear magnetic resonance and copper-nitroxide pulsed double electron-electron resonance, with molecular dynamics refinement, we localize the position of Cu(2+) in its high-affinity OR-bound state. Our results reveal an interdomain cis interaction that is stabilized by a conserved, negatively charged pocket of the globular domain. Interestingly, this interaction surface overlaps an epitope recognized by the POM1 antibody, the binding of which drives rapid cerebellar degeneration mediated by the PrP N terminus. The resulting structure suggests that the globular domain regulates the N-terminal domain by binding the Cu(2+)-occupied OR within a complementary pocket. PMID- 27265849 TI - LD Motif Recognition by Talin: Structure of the Talin-DLC1 Complex. AB - Cell migration requires coordination between integrin-mediated cell adhesion to the extracellular matrix and force applied to adhesion sites. Talin plays a key role in coupling integrin receptors to the actomyosin contractile machinery, while deleted in liver cancer 1 (DLC1) is a Rho GAP that binds talin and regulates Rho, and therefore actomyosin contractility. We show that the LD motif of DLC1 forms a helix that binds to the four-helix bundle of the talin R8 domain in a canonical triple-helix arrangement. We demonstrate that the same R8 surface interacts with the paxillin LD1 and LD2 motifs. We identify key charged residues that stabilize the R8 interactions with LD motifs and demonstrate their importance in vitro and in cells. Our results suggest a network of competitive interactions in adhesion complexes that involve LD motifs, and identify mutations that can be used to analyze the biological roles of specific protein-protein interactions in cell migration. PMID- 27265850 TI - Mechanism of Amyloidogenesis of a Bacterial AAA+ Chaperone. AB - Amyloids are fibrillar protein superstructures that are commonly associated with diseases in humans and with physiological functions in various organisms. The precise mechanisms of amyloid formation remain to be elucidated. Surprisingly, we discovered that a bacterial Escherichia coli chaperone-like ATPase, regulatory ATPase variant A (RavA), and specifically the LARA domain in RavA, forms amyloids under acidic conditions at elevated temperatures. RavA is involved in modulating the proper assembly of membrane respiratory complexes. LARA contains an N terminal loop region followed by a beta-sandwich-like folded core. Several approaches, including nuclear magnetic resonance spectroscopy and molecular dynamics simulations, were used to determine the mechanism by which LARA switches to an amyloid state. These studies revealed that the folded core of LARA is amyloidogenic and is protected by its N-terminal loop. At low pH and high temperatures, the interaction of the N-terminal loop with the folded core is disrupted, leading to amyloid formation. PMID- 27265852 TI - Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA. AB - CAD, the multienzymatic protein that initiates and controls de novo synthesis of pyrimidines in animals, associates through its aspartate transcarbamoylase (ATCase) domain into particles of 1.5 MDa. Despite numerous structures of prokaryotic ATCases, we lack structural information on the ATCase domain of CAD. Here, we report the structure and functional characterization of human ATCase, confirming the overall similarity with bacterial homologs. Unexpectedly, human ATCase exhibits cooperativity effects that reduce the affinity for the anti tumoral drug PALA. Combining structural, mutagenic, and biochemical analysis, we identified key elements for the necessary regulation and transmission of conformational changes leading to cooperativity between subunits. Mutation of one of these elements, R2024, was recently found to cause the first non-lethal CAD deficit. We reproduced this mutation in human ATCase and measured its effect, demonstrating that this arginine is part of a molecular switch that regulates the equilibrium between low- and high-affinity states for the ligands. PMID- 27265851 TI - The Structure of HIV-1 Rev Filaments Suggests a Bilateral Model for Rev-RRE Assembly. AB - HIV-1 Rev protein mediates the nuclear export of viral RNA genomes. To do so, Rev oligomerizes cooperatively onto an RNA motif, the Rev response element (RRE), forming a complex that engages with the host nuclear export machinery. To better understand Rev oligomerization, we determined four crystal structures of Rev N terminal domain dimers, which show that they can pivot about their dyad axis, giving crossing angles of 90 degrees to 140 degrees . In parallel, we performed cryoelectron microscopy of helical Rev filaments. Filaments vary from 11 to 15 nm in width, reflecting variations in dimer crossing angle. These structures contain additional density, indicating that C-terminal domains become partially ordered in the context of filaments. This conformational variability may be exploited in the assembly of RRE/Rev complexes. Our data also revealed a third interface between Revs, which offers an explanation for how the arrangement of Rev subunits adapts to the "A"-shaped architecture of the RRE in export-active complexes. PMID- 27265854 TI - Leukemic Cell Differentiation and the Signal Transduction System. PMID- 27265855 TI - Epstein-Barr Virus in Hodgkin's Disease Patients in Northeast Anatolia. AB - Epstein-Barr virus (EBV) is implicated as an etiologic factor in Hodgkin's disease (HD). The proportion of HD patients with EBV is high in developing countries but low in developed countries. In the present study, the EBV association with HD in Northeast Anatolia was investigated. Thirty-six formalin fixed paraffin-embedded cases of HD were analysed for the presence of EBV and, for the latent membrane protein (LPM-1) by immunohistochemistry. There were 26 males and 10 females; age distribution ranged from 12 to 73 years (mean +/- standard deviation, 34.1 +/- 15.2 years). Overall, LPM-1 was detected in 27 of the 36 cases (75%). LPM-1 expression varied according to the istological subtype of HD (9/55 cases of lymphocyte predominance subtype, 3/4 cases of nodular sclerosis, 18/18 cases of mixed cellularity subtype, and 1/5 cases of lymphocyte depletion subtype). In this study, the EBV-positivity ratio in HD was found extremely high in Northeast Anatolia. PMID- 27265853 TI - MtDNA and Y-chromosomal diversity in the Chachapoya, a population from the northeast Peruvian Andes-Amazon divide. AB - OBJECTIVES: The ancient Chachapoya were an aggregate of several ethnic groups that shared a common language, religion, and material culture. They inhabited a territory at the juncture of the Andes and the Amazon basin. Their position between those ecozones most likely influenced their genetic composition. We attempted to better understand their population history by assessing the contemporary genetic diversity in the Chachapoya and three of their immediate neighbors (Huancas, Jivaro, and Cajamarca). We inferred signatures of demographic history and genetic affinities, and contrasted the findings with data from other populations on local and continental scales. METHODS: We studied mitochondrial DNA (mtDNA; hypervariable segment [HVSI and HVSII]) and Y chromosome (23 short tandem repeats (STRs)) marker data in 382 modern individuals. We used Sanger sequencing for mtDNA and a commercially available kit for Y-chromosomal STR typing. RESULTS: The Chachapoya had affinities with various populations of Andean and Amazonian origin. When examining the Native American component, the Chachapoya displayed high levels of genetic diversity. Together with other parameters, for example, large Tajima's D and Fu's Fs, the data indicated no drastic reduction of the population size in the past. CONCLUSION: The high level of diversity in the Chachapoya, the lack of evidence of drift in the past, and genetic affinities with a broad range of populations in the Americas reflects an intricate population history in the region. The new genetic data from the Chachapoya indeed seems to point to a genetic complexity that is not yet resolved but beginning to be elucidated. Am. J. Hum. Biol. 28:857-867, 2016. (c) 2016Wiley Periodicals, Inc. PMID- 27265856 TI - The Incidence of Hepatitis G Virus in Patients with Hematological Malignancies: The Relationship to the Number of Blood and Blood Products Transfusions. AB - The hepatitis G virus has been detected in patients with post-transfusion hepatitis. The precise transmission rate of the hepatitis G virus is not clear. This study aims to investigate the transmission rate of HGV and the relationship between the number of blood transfusions and the blood products used in multitransfused patients with hematological malignancies. Serum samples were obtained from 80 patients with hematologic malignancies hospitalized between January 1997 and December 1998 at Ibn'i Sina Hospital, University of Ankara. The patients were divided into three groups according to transfusion numbers. Group A received between 0 and 10 units of blood and blood products, Group B received 10 20 units, and Group C received more than 20 units. All patients received blood and blood products for a median of 6.8 Units/whole life. The hepatitis G virus was detected using the reverse transcription polymerase chain reaction. Of the eighty patients, four (5.0 %) were HBs-Ag positive, one (1.25%) was Anti-HCV positive, and one (1.25%) was HGV-RNA positive. Multiple blood transfusions may be an important risk factor for transmission-transmitted viral infections, but based upon the present experience, there is no significant relationship between the number of blood transfusions and blood products and the transmission rate of HGV infection in patients with hematological malignancies. PMID- 27265857 TI - Activated Protein C Resistance in Behcet's Disease. AB - We investigated activated protein C resistance (aPCR) using modified activated partial thromboplastin time (aPTT) in 32 patients with Behcet's disease (BD) and 9 healthy controls. None of the healthy controls were found to have aPCR. However, 11 out of 32 Behcet's patients (34.3%) were found to have aPCR. The frequency of aPCR was increased to 44.4% among 18 Behcet's patients having a history of venous thrombosis. In the subgroup of 14 patients without venous thrombosis, aPCR frequency was %22.2. Our findings show that, besides other factors, aPCR may also predispose patients to venous thrombosis in BD. The detection of aPCR, using modified aPTT may serve as a routine screening test to determine the necessity of prophylactic anticoagulation reatment in patients with BD. PMID- 27265859 TI - Asecretory POEMS Syndrome with Widespread Osteosclerotic Lesions. AB - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) is a rare disease and constitues 1-2% of plasma cell dyscrasia. Most of the patients have few sclerotic bone lesions and more than 90% of patients have serum and/or urinary M-protein. In this report, we present a patient with POEMS syndrome who had severe polyneuropathy and unusual widespread osteosclerotic lesions without M- rotein in serum and urine. According to our knowledge, this is the first case of asecretory POEMS syndrome with multipl sclerotic lesions and polyneuropathy. Our patient is still well and able to work actively 4 years after diagnosis with the treatment of 12 courses of VAD by reducing the vincristine dosage. PMID- 27265858 TI - An Extra Benefit of Allogeneic Peripheral Blood Stem Cell Transplantation in a Patient with Lymphoblastic Lymphoma: Cure of Thalassemia Minor. AB - b thalassemia minor is frequent in mediterranean countries. It is a benign disorder and does not warrant any therapeutical intervention. We transplanted a 25-year-old Turkish male who was diagnosed as lymphoblastic lymphoma and had b thalassemia minor as well. He received peripheral blood stem cells transplantation from his HLA-identical sibling who was not a carrier of b thalassemia. After the allogeneic transplantation we did not only observe remission of the lymphoblastic lymphoma but also the disappearance of b thalassemia minor. PMID- 27265860 TI - Griscelli's Syndrome: Clinical and Immunological Features of Two Siblings. AB - Two siblings diagnosed with Griscelli's syndrome (GS) are presented. The clinical features were partial albinism, silvery hair and absence of giant granules in the white blood cells. The diagnosis of GS was confirmed at the ages of nine months and two months by the demonstation of irregular clumps of pigment in the hair shaft, a finding characteristic of this syndrome. The patients had hepatosplenomegaly and bone marrow examinations revealed Iymphohistiocytosis. Immunological studies revealed normal serum immunoglobulin levels and normal T and B Iymphocyte counts. Skin tests were positive for phytohemagglutinin and PPD in the first patient. Phagocytosis was studied by flow cytometry using Mo Ab (DCFH, PMA oxidative burst, Coulter) in the second sibling and it was found as normal. Splenectomy was performed in the second sibling because of excessive splenomegaly at the age of six months but she died two months later. The first sibling died at the age of 18 months because of infection. Postmortem examination of the siblings revealed Iymphohistiocytosis in the liver and spleen. PMID- 27265862 TI - Lymphoblastic Leukemic Infiltration of Breast. PMID- 27265861 TI - Images in Haematology. PMID- 27265863 TI - Nucleosomes determine their own patch size in base excision repair. AB - Base excision repair (BER) processes non-helix distorting lesions (e.g., uracils and gaps) and is composed of two subpathways that differ in the number of nucleotides (nts) incorporated during the DNA synthesis step: short patch (SP) repair incorporates 1 nt and long patch (LP) repair incorporates 2-12 nts. This choice for either LP or SP repair has not been analyzed in the context of nucleosomes. Initial studies with uracil located in nucleosome core DNA showed a distinct DNA polymerase extension profile in cell-free extracts that specifically limits extension to 1 nt, suggesting a preference for SP BER. Therefore, we developed an assay to differentiate long and short repair patches in 'designed' nucleosomes containing a single-nucleotide gap at specific locations relative to the dyad center. Using cell-free extracts or purified enzymes, we found that DNA lesions in the nucleosome core are preferentially repaired by DNA polymerase beta and there is a significant reduction in BER polymerase extension beyond 1 nt, creating a striking bias for incorporation of short patches into nucleosomal DNA. These results show that nucleosomes control the patch size used by BER. PMID- 27265865 TI - A conserved alternative form of the purple sea urchin HEB/E2-2/E2A transcription factor mediates a switch in E-protein regulatory state in differentiating immune cells. AB - E-proteins are basic helix-loop-helix (bHLH) transcription factors with essential roles in animal development. In mammals, these are encoded by three loci: E2-2 (ITF-2/ME2/SEF2/TCF4), E2A (TCF3), and HEB (ME1/REB/TCF12). The HEB and E2-2 paralogs are expressed as alternative (Alt) isoforms with distinct N-terminal sequences encoded by unique exons under separate regulatory control. Expression of these alternative transcripts is restricted relative to the longer (Can) forms, suggesting distinct regulatory roles, although the functions of the Alt proteins remain poorly understood. Here, we characterize the single sea urchin E protein ortholog (SpE-protein). The organization of the SpE-protein gene closely resembles that of the extended HEB/E2-2 vertebrate loci, including a transcript that initiates at a homologous alternative transcription start site (SpE-Alt). The existence of an Alt form in the sea urchin indicates that this feature predates the emergence of the vertebrates. We present additional evidence indicating that this transcript was present in the common bilaterian ancestor. In contrast to the widely expressed canonical form (SpE-Can), SpE-Alt expression is tightly restricted. SpE-Alt is expressed in two phases: first in aboral non skeletogenic mesenchyme (NSM) cells and then in oral NSM cells preceding their differentiation and ingression into the blastocoel. Derivatives of these cells mediate immune response in the larval stage. Inhibition of SpE-Alt activity interferes with these events. Notably, although the two isoforms are initially co expressed, as these cells differentiate, SpE-Can is excluded from the SpE-Alt(+) cell population. This mutually exclusive expression is dependent on SpE-Alt function, which reveals a previously undescribed negative regulatory linkage between the two E-protein forms. Collectively, these findings reorient our understanding of the evolution of this transcription factor family and highlight fundamental properties of E-protein biology. PMID- 27265864 TI - Pharyngeal morphogenesis requires fras1-itga8-dependent epithelial-mesenchymal interaction. AB - Both Fras1 and Itga8 connect mesenchymal cells to epithelia by way of an extracellular 'Fraser protein complex' that functions in signaling and adhesion; these proteins are vital to the development of several vertebrate organs. We previously found that zebrafish fras1 mutants have craniofacial defects, specifically, shortened symplectic cartilages and cartilage fusions that spare joint elements. During a forward mutagenesis screen, we identified a new zebrafish mutation, b1161, that we show here disrupts itga8, as confirmed using CRISPR-generated itga8 alleles. fras1 and itga8 single mutants and double mutants have similar craniofacial phenotypes, a result expected if loss of either gene disrupts function of the Fraser protein complex. Unlike fras1 mutants or other Fraser-related mutants, itga8 mutants do not show blistered tail fins. Thus, the function of the Fraser complex differs in the craniofacial skeleton and the tail fin. Focusing on the face, we find that itga8 mutants consistently show defective outpocketing of a late-forming portion of the first pharyngeal pouch, and variably express skeletal defects, matching previously characterized fras1 mutant phenotypes. In itga8 and fras1 mutants, skeletal severity varies markedly between sides, indicating that both mutants have increased developmental instability. Whereas fras1 is expressed in epithelia, we show that itga8 is expressed complementarily in facial mesenchyme. Paired with the observed phenotypic similarity, this expression indicates that the genes function in epithelial mesenchymal interactions. Similar interactions between Fras1 and Itga8 have previously been found in mouse kidney, where these genes both regulate Nephronectin (Npnt) protein abundance. We find that zebrafish facial tissues express both npnt and the Fraser gene fibrillin2b (fbn2b), but their transcript levels do not depend on fras1 or itga8 function. Using a revertible fras1 allele, we find that the critical window for fras1 function in the craniofacial skeleton is between 1.5 and 3 days post fertilization, which coincides with the onset of fras1-dependent and itga8-dependent morphogenesis. We propose a model wherein Fras1 and Itga8 interact during late pharyngeal pouch morphogenesis to sculpt pharyngeal arches through epithelial-mesenchymal interactions, thereby stabilizing the developing craniofacial skeleton. PMID- 27265866 TI - Redundant mechanisms are involved in suppression of default cell fates during embryonic mesenchyme and notochord induction in ascidians. AB - During embryonic induction, the responding cells invoke an induced developmental program, whereas in the absence of an inducing signal, they assume a default uninduced cell fate. Suppression of the default fate during the inductive event is crucial for choice of the binary cell fate. In contrast to the mechanisms that promote an induced cell fate, those that suppress the default fate have been overlooked. Upon induction, intracellular signal transduction results in activation of genes encoding key transcription factors for induced tissue differentiation. It is elusive whether an induced key transcription factor has dual functions involving suppression of the default fates and promotion of the induced fate, or whether suppression of the default fate is independently regulated by other factors that are also downstream of the signaling cascade. We show that during ascidian embryonic induction, default fates were suppressed by multifold redundant mechanisms. The key transcription factor, Twist-related.a, which is required for mesenchyme differentiation, and another independent transcription factor, Lhx3, which is dispensable for mesenchyme differentiation, sequentially and redundantly suppress the default muscle fate in induced mesenchyme cells. Similarly in notochord induction, Brachyury, which is required for notochord differentiation, and other factors, Lhx3 and Mnx, are likely to suppress the default nerve cord fate redundantly. Lhx3 commonly suppresses the default fates in two kinds of induction. Mis-activation of the autonomously executed default program in induced cells is detrimental to choice of the binary cell fate. Multifold redundant mechanisms would be required for suppression of the default fate to be secure. PMID- 27265869 TI - Recent Advances in Self-Oscillating Polymer Material Systems. AB - In 1996, we first reported self-oscillating polymer gels exhibiting autonomous swelling-deswelling oscillations driven by the Belousov-Zhabotinsky reaction. In contrast to conventional stimuli-responsive gels, the self-oscillating gel can autonomously and periodically change its volume in a closed solution without any external stimuli. Since the first report, the novel concept of self-oscillating gels has been expanded into various polymer and gel systems. Herein, we summarize recent advances in self-oscillating polymers and gels. PMID- 27265867 TI - Function of the C. elegans T-box factor TBX-2 depends on interaction with the UNC 37/Groucho corepressor. AB - T-box transcription factors are important regulators of development in all animals, and altered expression of T-box factors has been identified in an increasing number of diseases and cancers. Despite these important roles, the mechanism of T-box factor activity is not well understood. We have previously shown that the Caenorhabditis elegans Tbx2 subfamily member TBX-2 functions as a transcriptional repressor to specify ABa-derived pharyngeal muscle, and that this function depends on SUMOylation. Here we show that TBX-2 function also depends on interaction with the Groucho-family corepressor UNC-37. TBX-2 interacts with UNC 37 in yeast two-hybrid assays via a highly conserved engrailed homology 1 (eh1) motif located near the TBX-2 C-terminus. Reducing unc-37 phenocopies tbx-2 mutants, resulting in a specific loss of anterior ABa-derived pharyngeal muscles and derepression of the tbx-2 promoter. Moreover, double mutants containing hypomorphic alleles of unc-37 and tbx-2 exhibit enhanced phenotypes, providing strong genetic evidence that unc-37 and tbx-2 share common functions in vivo. To test whether interaction with UNC-37 is necessary for TBX-2 activity, we developed a transgene rescue assay using a tbx-2 containing fosmid and found that mutating the tbx-2 eh1 motif reduced rescue of a tbx-2 null mutant. These results indicate that TBX-2 function in vivo depends on interaction with UNC-37. As many T-box factors contain eh1 motifs, we suggest that interaction with Groucho-family corepressors is a common mechanism contributing to their activity. PMID- 27265868 TI - Ligand-induced substrate steering and reshaping of [Ag2(H)](+) scaffold for selective CO2 extrusion from formic acid. AB - Metalloenzymes preorganize the reaction environment to steer substrate(s) along the required reaction coordinate. Here, we show that phosphine ligands selectively facilitate protonation of binuclear silver hydride cations, [LAg2(H)](+) by optimizing the geometry of the active site. This is a key step in the selective, catalysed extrusion of carbon dioxide from formic acid, HO2CH, with important applications (for example, hydrogen storage). Gas-phase ion molecule reactions, collision-induced dissociation (CID), infrared and ultraviolet action spectroscopy and computational chemistry link structure to reactivity and mechanism. [Ag2(H)](+) and [Ph3PAg2(H)](+) react with formic acid yielding Lewis adducts, while [(Ph3P)2Ag2(H)](+) is unreactive. Using bis(diphenylphosphino)methane (dppm) reshapes the geometry of the binuclear Ag2(H)(+) scaffold, triggering reactivity towards formic acid, to produce [dppmAg2(O2CH)](+) and H2. Decarboxylation of [dppmAg2(O2CH)](+) via CID regenerates [dppmAg2(H)](+). These gas-phase insights inspired variable temperature NMR studies that show CO2 and H2 production at 70 degrees C from solutions containing dppm, AgBF4, NaO2CH and HO2CH. PMID- 27265871 TI - Safety climate, emotional exhaustion and job satisfaction among Brazilian paediatric professional nurses. AB - BACKGROUND: International studies indicate that job satisfaction and burnout interfere with the safety climate and quality of care. However, no evidence of such relationships is available for Brazilian paediatric hospitals. AIMS: To assess the correlation and predictive effect of emotional exhaustion and job satisfaction on the perception of professional nurses at paediatric hospitals regarding safety climate and quality of care. DESIGN: Cross-sectional correlational design. METHODS: The study was conducted with registered nurses, technician and assistant nurses from two Brazilian paediatric hospitals over 3 months in 2013-2014 using instruments to assess safety climate, quality of care, job satisfaction and emotional exhaustion. RESULTS: Data related to 267 professional nurses from 15 inpatient wards and 3 intensive care units were analysed. Overall, the respondents exhibited moderate emotional exhaustion, were satisfied with their jobs and considered the quality of care as good. However, the respondents exhibited low concordance as to the positive perception of the safety climate. The variables, emotional exhaustion and job satisfaction, exhibited significant correlations with safety climate and were considered predictive of the latter. CONCLUSION: Emotional exhaustion and job satisfaction among professional nurses influence the safety climate at paediatric hospitals. IMPLICATIONS FOR NURSING OR HEALTH POLICY: Investments to reduce emotional exhaustion and to improve job satisfaction among professional nurses allocated to paediatric hospitals might contribute to the patients' safety. PMID- 27265870 TI - Risk factors for subsequent febrile seizures in the FEBSTAT study. AB - OBJECTIVES: To identify risk and risk factors for developing a subsequent febrile seizure (FS) in children with a first febrile status epilepticus (FSE) compared to a first simple febrile seizure (SFS). To identify home use of rescue medications for subsequent FS. METHODS: Cases included a first FS that was FSE drawn from FEBSTAT and Columbia cohorts. Controls were a first SFS. Cases and controls were classified according to established FEBSTAT protocols. Cumulative risk for subsequent FS over a 5-year period was compared in FSE versus SFS, and Cox proportional hazards regression was conducted. Separate analysis examined subsequent FS within FSE. The use of rescue medications at home was assessed for subsequent FS. RESULTS: Risk for a subsequent FSE was significantly increased in FSE versus SFS. Any magnetic resonance imaging (MRI) abnormality increased the risk 3.4-fold (p < 0.05), adjusting for age at first FS and FSE and in analyses restricted to children whose first FS was FSE (any MRI abnormality hazard ratio [HR] 2.9, p < 0.05). The risk for a second FS of any type or of subsequent FS lasting >10 min over the 5-year follow-up did not differ in FSE versus SFS. Rectal diazepam was administered at home to 5 (23.8%) of 21 children with subsequent FS lasting >=10 min. SIGNIFICANCE: Compared to controls, FSE was associated with an increased risk for subsequent FSE, suggesting the propensity of children with an initial prolonged seizure to experience a prolonged recurrence. Any baseline MRI abnormality increased the recurrence risk when FSE was compared to SFS and when FSE was studied alone. A minority of children with a subsequent FS lasting 10 min or longer were treated with rectal diazepam at home, despite receiving prescriptions after the first FSE. This indicates the need to further improve the education of clinicians and parents in order to prevent subsequent FSE. PMID- 27265872 TI - The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly. AB - Disulfide bond formation is crucial for the biogenesis and structure of many proteins that are localized in the intermembrane space of mitochondria. The importance of disulfide bond formation within mitochondrial proteins was extended beyond soluble intermembrane space proteins. Tim22, a membrane protein and core component of the mitochondrial translocase TIM22, forms an intramolecular disulfide bond in yeast. Tim22 belongs to the Tim17/Tim22/Tim23 family of protein translocases. Here, we present evidence of the high evolutionary conservation of disulfide bond formation in Tim17 and Tim22 among fungi and metazoa. Topological models are proposed that include the location of disulfide bonds relative to the predicted transmembrane regions. Yeast and human Tim22 variants that are not oxidized do not properly integrate into the membrane complex. Moreover, the lack of Tim17 oxidation disrupts the TIM23 translocase complex. This underlines the importance of disulfide bond formation for mature translocase assembly through membrane stabilization of weak transmembrane domains. PMID- 27265873 TI - A novel TCR-like CAR with specificity for PR1/HLA-A2 effectively targets myeloid leukemia in vitro when expressed in human adult peripheral blood and cord blood T cells. AB - BACKGROUND AIMS: The PR1 peptide, derived from the leukemia-associated antigens proteinase 3 and neutrophil elastase, is overexpressed on HLA-A2 in acute myeloid leukemia (AML). We developed a T-cell receptor (TCR)-like monoclonal antibody (8F4) that binds the PR1/HLA-A2 complex on the surface of AML cells, efficiently killing them in vitro and eliminating them in preclinical models. Humanized 8F4 (h8F4) with high affinity for the PR1/HLA-A2 epitope was used to construct an h8F4- chimeric antigen receptor (CAR) that was transduced into T cells to mediate anti-leukemia activity. METHODS: Human T cells were transduced to express the PR1/HLA-A2-specific CAR (h8F4-CAR-T cells) containing the scFv of h8F4 fused to the intracellular signaling endo-domain of CD3 zeta chain through the transmembrane and intracellular costimulatory domain of CD28. RESULTS: Adult human normal peripheral blood (PB) T cells were efficiently transduced with the h8F4-CAR construct and predominantly displayed an effector memory phenotype with a minor population (12%) of central memory cells in vitro. Umbilical cord blood (UCB) T cells could also be efficiently transduced with the h8F4-CAR. The PB and UCB-derived h8F4-CAR-T cells specifically recognized the PR1/HLA-A2 complex and were capable of killing leukemia cell lines and primary AML blasts in an HLA-A2 dependent manner. CONCLUSIONS: Human adult PB and UCB-derived T cells expressing a CAR derived from the TCR-like 8F4 antibody rapidly and efficiently kill AML in vitro. Our data could lead to a new treatment paradigm for AML in which targeting leukemia stem cells could transfer long-term immunity to protect against relapse. PMID- 27265875 TI - Assessing the role of landscape connectivity on Opisthorchis viverrini transmission dynamics. AB - Opisthorchis viverrini (Ov) is one of the most important human parasitic diseases in Southeast Asia. Although the concept of connectivity is widely used to comprehend disease dispersal, knowledge of the influences of landscape connectivity on Ov transmission is still rudimentary. This study aimed to investigate the role of landscape connectivity in Ov transmission between the human and the first intermediate snail hosts. Fieldwork was conducted in three villages respectively in Kamalasai District, Kalasin Province, Phu Wiang District, Khon Kaen Province, and Nong Saeng District, Udon Thani Province. Bithynia snails were collected to examine parasitic infections, water samples were analyzed for fecal contamination, and locations of septic tanks and connections between habitat patches with observable water movement were surveyed. Euclidean distance, topological link and distance, and graph measures were employed to quantify the connectivity between human and snail habitats. The findings showed that snail patches with higher fecal contents were generally located nearer to septic tanks. The statistically significant results for the topological link and distance measures highlighted the importance of water in functionally facilitating Ov transmission. Graph measures revealed differences in landscape connectivity across the sites. The site with the largest landscape component size and the most mutually connected snail patches coincided with the presence of Ov parasite, reinforcing its higher risk for human to snail transmission. The site with the dissected landscape structure potentially limited the transmission. This study underscored the potential effect of landscape connectivity on Ov transmission, contributing to the understanding of the spatial variation of Ov infection risk. PMID- 27265874 TI - T-cell therapies for HIV: Preclinical successes and current clinical strategies. AB - Although antiretroviral therapy (ART) has been successful in controlling HIV infection, it does not provide a permanent cure, requires lifelong treatment, and HIV-positive individuals are left with social concerns such as stigma. The recent application of T cells to treat cancer and viral reactivations post-transplant offers a potential strategy to control HIV infection. It is known that naturally occurring HIV-specific T cells can inhibit HIV initially, but this response is not sustained in the majority of people living with HIV. Genetically modifying T cells to target HIV, resist infection, and persist in the immunosuppressive environment found in chronically infected HIV-positive individuals might provide a therapeutic solution for HIV. This review focuses on successful preclinical studies and current clinical strategies using T-cell therapy to control HIV infection and mediate a functional cure solution. PMID- 27265876 TI - Characterization and localization of Opisthorchis viverrini fructose-1,6 bisphosphate aldolase. AB - Opisthorchis viverrini (Ov) infection is a long-time public health problem in Thailand that can lead to bile duct cancer, cholangiocarcinoma (CCA). Characterization of the Ov proteins at a molecular level will increase our knowledge of host-parasite interaction that can be applied to new drug, vaccine, or immunodiagnostic development. In this study, an important enzyme in the Ov glycolytic pathway, fructose-1,6-bisphosphate aldolase (FBPA), that had been obtained from a previous study was characterized and immunolocalized. The full length sequence of OvFBPA gene is 1089bp and encodes 362 amino acids with a predicted molecular weight and isoelectric point of 39.54kDa and 7.61, respectively. Additionally, three OvFBPA isoforms were identified by sequence analysis. The amino acid sequence of OvFBPA-1 characterized in this study shared 98% identity to FBPA isoform 1 of Clonorchis sinensis that was classified based on highly conserved active residues to class-I FBPA. The recombinant OvFBPA-1 protein was expressed as a soluble form in Escherichia coli at 25 degrees C with N-terminal His-tagged fusion protein and the purified OvFBPA-1 protein was used to generate polyclonal antibody in mice. Antibody against rOvFBPA-1 protein was able to detect the native OvFBPA-1 protein in both Ov infected hamster liver section and Ov excretory-secretory (ES) products by immunohistochemistry and western blotting, respectively. PMID- 27265878 TI - Quantitative volcanic susceptibility analysis of Lanzarote and Chinijo Islands based on kernel density estimation via a linear diffusion process. AB - Risk management stakeholders in high-populated volcanic islands should be provided with the latest high-quality volcanic information. We present here the first volcanic susceptibility map of Lanzarote and Chinijo Islands and their submarine flanks based on updated chronostratigraphical and volcano structural data, as well as on the geomorphological analysis of the bathymetric data of the submarine flanks. The role of the structural elements in the volcanic susceptibility analysis has been reviewed: vents have been considered since they indicate where previous eruptions took place; eruptive fissures provide information about the stress field as they are the superficial expression of the dyke conduit; eroded dykes have been discarded since they are single non-feeder dykes intruded in deep parts of Miocene-Pliocene volcanic edifices; main faults have been taken into account only in those cases where they could modified the superficial movement of magma. The application of kernel density estimation via a linear diffusion process for the volcanic susceptibility assessment has been applied successfully to Lanzarote and could be applied to other fissure volcanic fields worldwide since the results provide information about the probable area where an eruption could take place but also about the main direction of the probable volcanic fissures. PMID- 27265877 TI - The between-day reproducibility of fasting, satiety-related analytes, in 8 to 11year-old boys. AB - The aim of the present study was to establish the between-day reproducibility of fasting plasma GLP-17-36, glucagon, leptin, insulin and glucose, in lean and overweight/obese 8-11year-old boys. A within-group study design was utilised wherein the boys attended two study days, separated by 1week, where a fasting fingertip capillary blood sample was obtained. Deming regression, mean difference, Bland-Altman limits of agreement (LOA) and typical imprecision as a percentage coefficient of variation (CV %), were utilised to assess reproducibility between-days. On a group level, Deming regression detected no evidence of systematic or proportional bias between-days for all of the satiety related analytes however, only glucose and plasma GLP-17-36 displayed low typical and random imprecision. When analysed according to body composition, good reproducibility was maintained for glucose in the overweight/obese boys and for plasma GLP-17-36, in those with lean body mass. The present findings demonstrate that the measurement of glucose and plasma GLP-17-36 by fingertip capillary sampling on a group level, is reproducible between-days, in 8-11year-old boys. Comparison of blood glucose obtained by fingertip capillary sampling can be made between lean and overweight/obese 8-11year-old boys. Presently, the comparison of fasting plasma GLP-17-36 according to body weight is inappropriate due to high imprecision observed in lean boys between-days. The use of fingertip capillary sampling in the measurement of satiety-related analytes has the potential to provide a better understanding of mechanisms that affect appetite and feeding behaviour in children. PMID- 27265879 TI - Peptic Ulcer Disease and Helicobacter pylori Infection in Different Siberian Ethnicities. AB - BACKGROUND: The high prevalence of Helicobacter pylori (H. pylori) infection in eastern Siberia is consistently established. In the same geographic area, however, fragmentary information is available on the epidemiology of the peptic ulcer disease (PUD). AIM: To assess the prevalence of H. pylori infection (including CagA status) and PUD in different eastern Siberian ethnicities. PATIENTS AND METHODS: An endoscopy population of 3149 eastern Siberian dyspeptic patients was considered [1727 Europoids and 1422 Mongoloids (Evenks = 792; Khakases = 630)]. H. pylori status was assessed by urease test and/or serum anti H. pylori IgG and/or histology. CagA status was serologically assessed (anti-CagA antibodies). RESULTS: All the Siberian ethnicities featured high rates of H. pylori infection (Europoids = 87.1%, Evenks = 88.6%, Khakases = 85.4%). Among the 1504 H. pylori-positive Europoids, the prevalence of CagA-positive status (68.7%) was significantly higher than that featured by the 1240 H. pylori-positive Mongoloid ethnicities (46.9%; p < .001 for both comparisons). Peptic ulcer disease significantly prevailed among Europoids (prevalence among Europoid Evenks and Khakases: 8.9% and 8.3%, respectively; prevalence among Mongoloid Evenks and Khakases = 1.0% and 4.4%, respectively). CONCLUSIONS: eastern Siberian populations feature consistent high rates of H. pylori infection, but different prevalence of peptic ulcer disease. In particular, Europoids featured a prevalence of both CagA-positive status and peptic ulcer disease significantly higher than that of the Mongoloid ethnicities. These results suggest that both environmental factors (coexisting with the H. pylori infection) and host-related variables modulate the clinicopathological expression of the H. pylori associated gastric diseases. PMID- 27265881 TI - A Powerful Chiral Phosphoric Acid Catalyst for Enantioselective Mukaiyama-Mannich Reactions. AB - A new BINOL-derived chiral phosphoric acid bearing 2,4,6-trimethyl-3,5 dinitrophenyl substituents at the 3,3'-positions was developed. The utility of this chiral phosphoric acid is demonstrated by a highly enantioselective (ee up to >99 %) and diastereoselective (syn/anti up to >99:1) asymmetric Mukaiyama Mannich reaction of imines with a wide range of ketene silyl acetals. Moreover, this method was successfully applied to the construction of vicinal tertiary and quaternary stereogenic centers with excellent diastereo- and enantioselectivity. Significantly, BINOL-derived N-triflyl phosphoramide constitutes a complementary catalyst system that allows the title reaction to be applied to more challenging imines without an N-(2-hydroxyphenyl) moiety. PMID- 27265880 TI - Clinical efficacy and safety of mirabegron and imidafenacin in women with overactive bladder: A randomized crossover study (the MICRO study). AB - AIMS: We aimed to compare the efficacy and safety of mirabegron, a beta3 adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients. METHODS: We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged >=50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50 mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2 mg per day) for 8 weeks. This order of drug administration was reversed in Group B. RESULTS: A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24 hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not. CONCLUSIONS: Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 36:1097-1103, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27265882 TI - Prostaglandin E2 promotes neural proliferation and differentiation and regulates Wnt target gene expression. AB - Prostaglandin E2 (PGE2 ) is an endogenous lipid molecule that regulates important physiological functions, including calcium signaling, neuronal plasticity, and immune responses. Exogenous factors such as diet, exposure to immunological agents, toxic chemicals, and drugs can influence PGE2 levels in the developing brain and have been associated with autism disorders. This study seeks to determine whether changes in PGE2 level can alter the behavior of undifferentiated and differentiating neuroectodermal (NE-4C) stem cells and whether PGE2 signaling impinges on the Wnt/beta-catenin pathways. We show that PGE2 increases proliferation of undifferentiated NE-4C stem cells. PGE2 also promotes the progression of NE-4C stem cell differentiation into neuronal-lineage cells, which is apparent by accelerated appearance of neuronal clusters (neurospheres) and earlier expression of the neuronal marker microtubule associated protein tau. Furthermore, PGE2 alters the expression of downstream Wnt regulated genes previously associated with neurodevelopmental disorders. In undifferentiated stem cells, PGE2 downregulates Ptgs2 expression and upregulates Mmp9 and Ccnd1 expression. In differentiating neuronal cells, PGE2 causes upregulation of Wnt3, Tcf4, and Ccnd1. The convergence of the PGE2 and the Wnt pathways is also apparent through increased expression of active beta-catenin, a key signaling component of the Wnt/beta-catenin pathways. This study provides novel evidence that PGE2 influences progression of neuronal development and influences Wnt target gene expression. We discuss how these findings could have potential implications for neurodevelopmental disorders such as autism. (c) 2016 Wiley Periodicals, Inc. PMID- 27265883 TI - Dental insurance and dental care among working-age adults: differences by type and complexity of disability. AB - OBJECTIVES: People with disabilities experience barriers to dental care, which may vary depending on type of disability and disability complexity (e.g., impact on activities of daily living). The purpose of this study was to examine differences in dental insurance, receipt of dental checkups, and delayed and unmet needs for dental care by type and complexity of disability. METHODS: We conducted cross-sectional analysis of 2002-2011 data from the Medical Expenditure Panel Survey. Multivariable logistic regression analyses compared adults ages 18 64 in five disability type groups (physical, cognitive, vision, hearing, or multiple disabilities) to those with no disabilities, and compared people with complex activity limitations to those without complex limitations. RESULTS: All disability types except hearing had significantly higher adjusted odds of being without dental insurance, as did people with complex activity limitations. All disability groups except those with cognitive disabilities had increased odds of receiving dental checkups less than once a year. Similarly, all disability groups were at increased risk of both delayed and unmet needs for dental care. Odds ratios were generally highest for people with multiple types of disabilities. CONCLUSIONS: There are significant disparities in having dental insurance and receiving dental care for adults with disabilities, especially those with multiple types of disabilities, after controlling for socioeconomic and demographic differences. Further, disparities in care were apparent even when controlling for presence of dental insurance. PMID- 27265884 TI - Proteomic and physiological responses of Arabidopsis thaliana exposed to salinity stress and N-acyl-homoserine lactone. AB - To evaluate the alleviating action of exogenous N-acyl-homoserine lactones (AHLs) on NaCl toxicity, morphological, physiological and proteomic changes were investigated in Arabidopsis thaliana seedlings. Salinity stress decreased growth parameters, increased malondialdehyde (MDA) contents and antioxidant enzymes such as superoxide dismutase (SOD), guaiacol peroxidase (POD) and catalase activities. Application of lower concentration of AHL had a relieving effect on Arabidopsis seedlings under salinity stress which dramatically decreased MDA content, and increased growth parameters as well as SOD and POD activities. Total proteins were extracted from the control, NaCl-, AHL- and NaCl + AHL-treated seedlings and were separated using two-dimensional gel electrophoresis. A total of 127 protein spots showed different expression compared with the control. Mass spectrometry analysis allowed the identification of 97 proteins involved in multiple pathways, i.e. defense/stress/detoxification, photosynthesis, protein metabolism, signal transduction, transcription, cell wall biogenesis, metabolisms of carbon, lipid, energy, sulfur, nucleotide and sugar. These results suggest that defense/stress response, metabolism and energy, signal transduction and regulation, protein metabolism and transcription-related proteins may be particularly subjected to regulation in salt stressed Arabidopsis seedlings, when treated with AHL and that this regulation lead to improved salt tolerance and plant growth. Overall, this study provides insight to the effect of AHL on salinity stress for the first time, and also sheds light on overview of the molecular mechanism of AHL regulated plant growth promotion and salt resistance. PMID- 27265886 TI - Reply. PMID- 27265885 TI - Simultaneous anterior and posterior serosal mapping of gastric slow-wave dysrhythmias induced by vasopressin. AB - NEW FINDINGS: What is the central question of this study? This study aimed to provide the first comparison of simultaneous high-resolution mapping of anterior and posterior gastric serosa over sustained periods. What is the main finding and its importance? Episodes of spontaneous gastric slow-wave dysrhythmias increased significantly following intravenous infusion of vasopressin compared with the baseline state. A number of persistent dysrhythmias were defined, including ectopic activation, conduction block, rotor, retrograde and collision/merger of wavefronts. Slow-wave dysrhythmias could occur either simultaneously or independently on the anterior and posterior gastric serosa, and interacted depending on activation-repolarization and frequency dynamics. High-resolution mapping enables mechanistic insights into gastric slow-wave dysrhythmias and is now achieving clinical translation. However, previous studies have focused mainly on dysrhythmias occurring on the anterior gastric wall. The present study simultaneously mapped the anterior and posterior gastric serosa during episodes of dysrhythmias induced by vasopressin to aid understanding of dysrhythmia initiation, maintenance and termination. High-resolution mapping (8 * 16 electrodes on each serosa; 20-74 cm2 ) was performed in anaesthetized dogs. Baseline recordings (21 +/- 8 min) were followed by intravenous infusion of vasopressin (0.1-0.5 IU ml-1 at 60-190 ml h-1 ) and further recordings (22 +/- 13 min). Slow-wave activation maps, amplitudes, velocity, interval and frequency were calculated, and differences compared between baseline and postinfusion. All dogs demonstrated an increased prevalence of dysrhythmic events following infusion of vasopressin (17 versus 51%). Both amplitude and velocity demonstrated significant differences (baseline versus postinfusion: 3.6 versus 2.2 mV; 7.7 versus 6.5 mm s-1 ; P < 0.05 for both). Dysrhythmias occurred simultaneously or independently on the anterior and posterior serosa, and then interacted according to frequency dynamics. A number of persistent dysrhythmias were compared, including the following: ectopic activation (n = 2 animals), conduction block (n = 1), rotor (n = 2), retrograde (n = 3) and collision/merger of wavefronts (n = 2). We conclude that infusion of vasopressin induces gastric dysrhythmias, which occur across a heterogeneous range of frequencies and patterns. The results demonstrate that different classes of gastric dysrhythmias may arise simultaneously or independently in one or both surfaces of the serosa, then interact according to their relative frequencies. These results will help to inform interpretation of clinical dysrhythmia. PMID- 27265887 TI - Efficacy of the epilepsy nurse: Results of a randomized controlled study. AB - OBJECTIVE: We investigated the efficacy of epilepsy nurses on satisfaction with counseling about epilepsy in a randomized, controlled, prospective trial. METHODS: Patients with epilepsy treated by neurologists in outpatient clinics were consecutively enrolled and randomly allocated to either the epilepsy nurse (EN) group (n = 92) or the control group (n = 95). Patients in the EN group were advised according to their needs by epilepsy nurses. The control group received routine care without additional counseling. The EN group completed the questionnaires before the first consultation (T1) and 6 months later (T2); the control group completed the questionnaires twice with an interval of 6 months. Primary outcome measure was satisfaction of patients with information and support. Secondary outcome measures were satisfaction with patient-doctor relationship, organization of treatment, epilepsy knowledge, coping, and restrictions in daily life. Anxiety and depression (Hospital Anxiety and Depression Scale) and global Quality of Life (item from QOLIE-31) were also assessed. Statistical analysis included generalized estimating equation (GEE) and nonparametric tests. RESULTS: Satisfaction with information and support improved significantly in the EN group compared to the control group (GEE, interaction group * time, p = 0.001). In addition, Epilepsy Knowledge (p = 0.014) and Coping (subscale Information Seeking) (p = 0.023) improved. Increase in satisfaction with counseling was dependent on patients' needs for information and on the amount of received information (Jonckheere-Terpstra test, p < 0.001). No differences between the groups were observed on other epilepsy-specific scales. SIGNIFICANCE: A reliable questionnaire for satisfaction with epilepsy care has been developed. Epilepsy nurses improve the satisfaction of patients with counseling and information about epilepsy and concomitant problems. PMID- 27265888 TI - Recurrent laryngeal nerve injury in thyroid surgery: Clinical pathways and resources consumption. AB - BACKGROUND: The impact of recurrent laryngeal nerve (RLN) injury management in thyroid surgery seems to be relevant to patients, National Healthcare System (NHS), and society. METHODS: We studied resource consumption in the management of patients with RLN injury versus noninjured patients investigating 3 perspectives (patients, NHS, and society) in 5 clinical pathways. RESULTS: Direct medical costs supported by the NHS range from a minimum of euro (?) 79.46 to a maximum of ? 3261.95. From the patient's perspective, the direct medical costs supported by the patient increased from a minimum of ? 3.60 to a maximum of ? 499.45. Productivity losses were accounted in ? 156 per day per patient. From the NHS perspective, the percentage increase ranged from 43.25% to 98.14%. From the patient's perspective, it ranged from 51.52% to 80.60%. CONCLUSION: The analysis shows a significant economic impact of RLN injury management, which varies depending on the damage, duration, and severity. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016. PMID- 27265889 TI - Plant Growth-Promoting Microorganisms for Environmental Sustainability. AB - Agrochemicals used to meet the needs of a rapidly growing human population can deteriorate the quality of ecosystems and are not affordable to farmers in low resource environments. Here, we propose the use of plant growth-promoting microorganisms (PGPMs) as a tool for sustainable food production without compromising ecosystems services. PMID- 27265890 TI - Regulation of Glucose Metabolism - A Perspective From Cell Bioprocessing. AB - Cultured mammalian cells are the main workhorses for producing biologics. The performance of these cell culture processes, in terms of both productivity and product quality attributes, is significantly influenced by cellular metabolism. Glucose is the major carbon source for cellular biosynthesis and energy generation. We summarize here recent advances in our understanding of the regulation of glucose metabolism in cultured cells. The versatility of cells to sustain homeostatic states under widely varying environments is made possible by allosteric regulation of the metabolic network, interplay between the signaling pathways, and transcription factors. Understanding the regulation of metabolism holds the key to altering the metabolic regulatory circuit and implementing direct metabolic control over cell culture processes. PMID- 27265892 TI - Linking. PMID- 27265891 TI - Return of the lysergamides. Part II: Analytical and behavioural characterization of N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ). AB - Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N6 -allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the 'research chemicals'/new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioural responses via activation of 5-HT2A receptors. Both AL-LAD and LSZ displayed LSD like responses in male C57BL/6 J mice when employing the head-twitch response (HTR) assay. AL-LAD and LSZ produced nearly identical inverted-U-shaped dose dependent effects, with the maximal responses occurring at 200 ug/kg. Analysis of the dose responses by nonlinear regression confirmed that LSZ (ED50 = 114.2 nmol/kg) was equipotent to LSD (ED50 = 132.8 nmol/kg) in mice, whereas AL-LAD was slightly less potent (ED50 = 174.9 nmol/kg). The extent to which a comparison in potency can be translated directly to humans requires further investigation. Chemical and pharmacological data obtained from NPS may assist research communities that are interested in various aspects related to substance use and forensic identification. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27265893 TI - Baseline factors associated with glycaemic response to treatment with once-weekly dulaglutide in patients with type 2 diabetes. AB - Dulaglutide glycaemic efficacy has been demonstrated in the AWARD clinical trial programme. The objective of the present analysis was to determine the major baseline factors associated with the reduction in glycated haemoglobin (HbA1c) in response to dulaglutide. Baseline covariates from patients receiving dulaglutide in six phase III studies (n = 2806) were analysed using a gradient-boosting method to assess their relative influence on the change in HbA1c after 26 weeks of treatment. Influential variables (relative influence >5%) were further evaluated in univariate and multivariable modelling. The gradient-boosting analysis showed that the top influential baseline factors associated with HbA1c reduction were: HbA1c (48.8%), age (9.1%), fasting serum glucose (FSG; 8.2%), fasting serum insulin (FSI; 6.7%) and estimated glomerular filtration rate (eGFR; 5.4%). Multivariable regression showed that higher baseline HbA1c was the major factor associated with greater HbA1c reduction [coefficient estimates: -0.6% ( 6.6 mmol/mol); p < 0.0001]. Age <=65 years, lower FSG level, FSI level <=55 pmol/L and eGFR <=100 mL/min/1.73 m2 were associated with greater decreases in HbA1c, but the effect was very small [coefficient estimates: -0.05% to -0.2% ( 0.6 to -2.2 mmol/mol)]. These data indicate that higher baseline HbA1c, reflecting poor glycaemic status, is the major factor associated with greater reduction in HbA1c in response to dulaglutide treatment. PMID- 27265894 TI - Neuroprotective and anti-inflammatory effects of morin in a murine model of Parkinson's disease. AB - Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that oxidative stress, mitochondrial dysfunction, and inflammation are associated with its pathogenesis. Morin (3,5,7,2',4'-pentahydroxyflavone) is a flavonol found in wine and many herbs and fruits. Previous studies have suggested that morin prevents oxidative damage and inflammation and ameliorates mitochondrial dysfunction. The present study describes the neuroprotective effects of morin in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and we report the results of our investigation into its neuroprotective mechanism in primary neurons and astrocytes. In the mouse model, morin pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in SN and striatum, and alleviated MPTP-induced astrocyte activation. In vitro studies revealed that morin protected primary cultured neurons against 1-methyl-4 phenylpyridine (MPP(+) )-mediated reactive oxygen species production and mitochondrial membrane potential (MMP) disruption. In addition, morin effectively reduced MPP(+) -induced astroglial activation and nuclear translocation of nuclear factor-kappaB in primary cultured astrocytes. These results indicate that morin acts via multiple neuroprotective mechanisms in our mouse model and suggest that morin be viewed as a potential treatment and preventative for PD. (c) 2016 Wiley Periodicals, Inc. PMID- 27265896 TI - Enantioselective Intramolecular C-H Insertion of Donor and Donor/Donor Carbenes by a Nondiazo Approach. AB - The first enantioselective intramolecular C-H insertion and cyclopropanation reactions of donor- and donor/donor-carbenes by a nondiazo approach are reported. The reactions were conducted in a one-pot manner without slow addition and provided the desired dihydroindole, dihydrobenzofuran, tetrahydrofuran, and tetrahydropyrrole derivatives with up to 99 % ee and 100 % atom efficiency. PMID- 27265895 TI - Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B cell precursor acute lymphoblastic leukaemia. AB - Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease. PMID- 27265897 TI - Identification of oral bacteria on titanium implant surfaces by 16S rDNA sequencing. AB - OBJECTIVE: To characterize the profile of microbial communities colonizing titanium implants with different surface treatments after exposure to the oral environment at the genus or higher taxonomic level. MATERIAL AND METHODS: Sixteen titanium disks, machined or sandblasted large-grit and acid-etched (SLA), were mounted on removable intraoral splints worn by four patients. After 24 h of intraoral exposure, biofilm samples were collected from disks and supra/subgingival teeth areas. The 16S rDNA genes from each sample were amplified, sequenced with the Miseq Illumina instrument and analyzed. RESULTS: A total of 29 genera and seven more inclusive taxa, representing the phyla Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, Actinobacteria and candidate division TM7 were identified in both titanium surfaces and teeth. No differences were found in relation to the operational taxonomic units (OTUs) and microbial diversity, assessed by Chao 1 and Shannon indices, when comparing SLA and machined titanium surfaces. CONCLUSIONS: Machined and SLA surfaces are colonized by similar numbers of prokaryotic OTUs after 24 h of exposure to the oral environment. Higher complexity of the titanium surface topography in the initial phase of biofilm maturation does not seem to significantly influence the colonizing microbiota. PMID- 27265899 TI - The analytical and biomedical potential of cytosine-rich oligonucleotides: A review. AB - Polycytosine DNA strands are often found among natural sequences, including the ends of telomeres, centromeres, and introns or in the regulatory regions of genes. A characteristic feature of oligonucleotides that are rich in cytosine (C rich) is their ability to associate under acidic conditions to form a tetraplex i motif consisting of two parallel stranded cytosine-hemiprotonated cytosine (C.C+) base-paired duplexes that are mutually intercalated in an antiparallel orientation. Nanotechnology has been exploiting the advantages of i-motif pH dependent formation to fabricate nanomachines, nanoswitches, electrodes and intelligent nanosurfaces or nanomaterials. Although a few reviews regarding the structure, properties and applications of i-motifs have been published, this review focuses on recently developed biosensors (e.g., to detect pH, glucose or silver ions) and drug-delivery biomaterials. Furthermore, we have included examples of sensors based on parallel C-rich triplexes and silver nanoclusters (AgNCs) fabricated on cytosine-rich DNA strands. The potential diagnostic and therapeutic applications of this type of material are discussed. PMID- 27265898 TI - Effect of surgical intervention on circulating tumor cells in patients with squamous cell carcinoma of the head and neck using a negative enrichment technology. AB - BACKGROUND: The purpose of this study was to investigate the impact of surgical intervention on detection of circulating tumor cells (CTCs) in patients with squamous cell carcinoma of the head and neck (SCCHN.) METHODS: We utilized a negative depletion technique to identify cytokeratin (CK)-positive CTCs. The numbers of CTCs immediately before and after surgical resection were compared. RESULTS: Seventy-six blood samples from 38 patients with SCCHN were examined. Seventy-nine percent of the patients had CTCs detected before and after surgery. A total of 7.89% had no CTCs before surgery, yet had CTCs identified after surgery. Overall, 60.5% of patients had an increased number of CTCs/mL after surgery with a mean increase of 6.63-fold. A statistically significant increase in CTCs was seen after surgery (p = .02). CONCLUSION: The timing of sample collection in patients with SCCHN who have surgical intervention can potentially impact the number of CTCs identified. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1799-1803, 2016. PMID- 27265900 TI - Improving global feature detectabilities through scan range splitting for untargeted metabolomics by high-performance liquid chromatography-Orbitrap mass spectrometry. AB - Untargeted metabolomics aims at obtaining quantitative information on the highest possible number of low-molecular biomolecules present in a biological sample. Rather small changes in mass spectrometric spectrum acquisition parameters may have a significant influence on the detectabilities of metabolites in untargeted global-scale studies by means of high-performance liquid chromatography-mass spectrometry (HPLC-MS). Employing whole cell lysates of human renal proximal tubule cells, we present a systematic global-scale study of the influence of mass spectrometric scan parameters and post-acquisition data treatment on the number and intensity of metabolites detectable in whole cell lysates. Ion transmission and ion collection efficiencies in an Orbitrap-based mass spectrometer basically depend on the m/z range scanned, which, ideally, requires different instrument settings for the respective mass ranges investigated. Therefore, we split a full scan range of m/z 50-1000 relevant for metabolites into two separate segments (m/z 50-200 and m/z 200-1,000), allowing an independent tuning of the ion transmission parameters for both mass ranges. Three different implementations, involving either scanning from m/z 50-1000 in a single scan, or scanning from m/z 50-200 and from m/z 200-1000 in two alternating scans, or performing two separate HPLC-MS runs with m/z 50-200 and m/z 200-1000 scan ranges were critically assessed. The detected features were subjected to rigorous background filtering and quality control in order to obtain reliable metabolite features for subsequent differential quantification. The most efficient approach in terms of feature number, which forms the basis for statistical analysis, identification, and for generating biological hypotheses, was the separate analysis of two different mass ranges. This lead to an increase in the number of detectable metabolite features, especially in the higher mass range (m/z greater than 400), by 2.5 (negative mode) to 6-fold (positive mode) as compared to analysis involving a single scan range. The total number of features confidently detectable was 560 in positive ion mode, and 436 in negative ion mode. PMID- 27265901 TI - Catalytic and peroxidase-like activity of carbon based-AuPd bimetallic nanocomposite produced using carbon dots as the reductant. AB - In this report, carbon-based AuPd bimetallic nanocomposite (AuPd/C NC) was synthesized using carbon dots (C-dots) as the reducing agent and stabilizer by a simple green sequential reduction strategy, without adding other agents. The as synthesized AuPd/C NC showed good catalytic activity and peroxidase-like property. The structure and morphology of these nanoparticles were clearly characterized by UV-Vis spectroscopy, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The AuPd/C NC catalyst exhibits noticeably higher catalytic activity than Pd and Au nanoparticles in catalysis reduction of 4-nitrophenol (4-NP). Moreover, based on the high peroxidase-like property of AuPd/C NC, a new colorimetric detection method for hydrogen peroxide (H2O2) has been designed using 3,3',5,5'-tetramethyl-benzidine (TMB) as the substrate, which provides a simple and sensitive means to detect H2O2 in wide linear range of 5 MUM-500 MUM and 500 MUM-4 mM with low detection limit of 1.6 MUM (S/N = 3). Therefore, the facile synthesis strategy for bimetallic nanoparticles by the mild reductant of carbon dot will provide some new thoughts for preparing of carbon-based metal nanomaterials and expand their application in catalysis and analytical chemistry areas. PMID- 27265902 TI - Label-free nanoplasmonic sensing of tumor-associate autoantibodies for early diagnosis of colorectal cancer. AB - Colorectal cancer is treatable and curable when detected at early stages. However there is a lack of less invasive and more specific screening and diagnosis methods which would facilitate its prompt identification. Blood circulating autoantibodies which are immediately produced by the immune system at tumor appearance have become valuable biomarkers for preclinical diagnosis of cancer. In this work, we present the rapid and label-free detection of colorectal cancer autoantibodies directly in blood serum or plasma using a recently developed nanoplasmonic biosensor. Our nanoplasmonic device offers sensitive and real-time quantification of autoantibodies with excellent selectivity and reproducibility, achieving limits of detection around 1 nM (150-160 ng mL(-1)). A preliminary evaluation of clinical samples of colorectal cancer patients has shown good correlation with ELISA. These results demonstrate the reliability of the nanobiosensor strategy and pave the way towards the achievement of a sensitive diagnostic tool for early detection of colorectal cancer. PMID- 27265903 TI - Mapping molecular adhesion sites inside SMIL coated capillaries using atomic force microscopy recognition imaging. AB - Capillary zone electrophoresis (CZE) is a powerful analytical technique for fast and efficient separation of different analytes ranging from small inorganic ions to large proteins. However electrophoretic resolution significantly depends on the coating of the inner capillary surface. High technical efforts like Successive Multiple Ionic Polymer Layer (SMIL) generation have been taken to develop stable coatings with switchable surface charges fulfilling the requirements needed for optimal separation. Although the performance can be easily proven in normalized test runs, characterization of the coating itself remains challenging. Atomic force microscopy (AFM) allows for topographical investigation of biological and analytical relevant surfaces with nanometer resolution and yields information about the surface roughness and homogeneity. Upgrading the scanning tip to a molecular biosensor by adhesive molecules (like partly inverted charged molecules) allows for performing topography and recognition imaging (TREC). As a result, simultaneously acquired sample topography and adhesion maps can be recorded. We optimized this technique for electrophoresis capillaries and investigated the charge distribution of differently composed and treated SMIL coatings. By using the positively charged protein avidin as a single molecule sensor, we compared these SMIL coatings with respect to negative charges, resulting in adhesion maps with nanometer resolution. The capability of TREC as a functional investigation technique at the nanoscale was successfully demonstrated. PMID- 27265904 TI - Methodological Contributions about Systolic Pulmonary Artery Pressure. Reply. PMID- 27265905 TI - Editor's Note. PMID- 27265906 TI - [Not Available]. PMID- 27265908 TI - Introduction. PMID- 27265907 TI - [Not Available]. PMID- 27265909 TI - [Retraction: Elevation of direct susceptibility testing from blood culture bottles. Clinical usefulness]. PMID- 27265910 TI - In memoriam--Vivek Singh. PMID- 27265911 TI - Professor Francis William O'Grady, 7 November 1925-20 May 2015. PMID- 27265912 TI - Guest Editorial-Selected Papers from the 2015 IEEE International Solid-State Circuits Conference. PMID- 27265913 TI - Ipilimumab-Induced Autoimmune Hypophysitis: Diagnostic and Management Challenges Illustrated by a Clinical Case. AB - Autoimmune hypophysitis has been described in patients on ipilimumab, a humanised monoclonal antibody increasingly used in the treatment of metastatic melanoma. A 67-year-old woman presented with severe fatigue, nausea and headaches following the third dose of ipilimumab, which was being given as treatment for metastatic melanoma (four administrations at three-weekly intervals). Hormonal evaluation confirmed hypocortisolism, with low gonadotrophins and a low thyroid-stimulating hormone with normal free T4 (she was on long-standing levothyroxine because of past surgery for a multinodular goitre). Magnetic resonance imaging scanning revealed pituitary enlargement compatible with autoimmune hypophysitis. She was commenced on replacement with hydrocortisone with significant improvement of her symptoms. The enlarged pituitary was reduced in size 4 months later. The patient is currently asymptomatic on glucocorticoid and levothyroxine replacement. This case highlights relevant clinical, diagnostic and management aspects of ipilimumab-induced autoimmune hypophysitis, and emphasises the need for increasing awareness for potential side-effects of these new immunomodulatory therapies, including autoimmune hypophysitis. PMID- 27265915 TI - Averting Malpractice Issues in Today's Nursing Practice. PMID- 27265914 TI - Issues Confronting the Nursing Profession Today. PMID- 27265916 TI - From the SEMA. PMID- 27265917 TI - From the NATO SOF Surgeon. PMID- 27265918 TI - Committee for Tactical Emergency Casualty Care. Spring Update. PMID- 27265919 TI - From the PUBLISHER and EDITOR. PMID- 27265920 TI - From the SOMA PRESIDENT. PMID- 27265921 TI - The Use of an Indwelling Catheter Protocol to Reduce Rates of Postoperative Urinary Tract Infections. AB - BACKGROUND: Catheter-associated urinary tract infections (CAUTI) have been associated with increases in morbidity and mortality as well as increased costs of hospitalization. At our institution, we implemented a protocol for indwelling catheter use, maintenance, and removal based on Center for Medicare and Medicaid Services (CMS) guidelines, in efforts to reduce CAUTI rates. METHODS: A hospital committee of quality stewards focused on several measures which included staff education, modification of existing systems to ensure compliance, and auditing of patient care areas for catheter utilization before implementation of the protocol. Pre- and postintervention postoperative cohorts were then identified through American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) for prevalence of CAUTI. Data were collected through chart review and postdischarge patient interviews. RESULTS: A total of 3873 patients were identified between September 2007 and December 2010. Thirty-six patients (2.6%) were diagnosed with a CAUTI in the preintervention group (N = 1404) compared to 38 (1.5%) patients who were diagnosed with a CAUTI in the postintervention group (N = 2469). There was a 1.1% decrease in CAUTI rate after protocol implementation (P < .028). This reduction in rates resulted in annual estimated savings of $81,840 to $320,540 annually. CONCLUSION: A simple, multifaceted approach consisting of staff education and changing existing processes to reflect best care practices has the potential to significantly reduce the incidence of postoperative CAUTI. PMID- 27265922 TI - CVAS: A Rapid Dysphagia Evaluation Tool. AB - A simple-to-administer test for dysphagia was developed at our institution. The test can be administered rapidly and easily in the Emergency Department (ED) by a nurse or other qualified medical person, making formal consultation with a speech pathologist for rapid determination of dysphagia unnecessary. Our study shows that the use of the test does not increase the incidence of aspiration pneumonia. PMID- 27265923 TI - Primary Squamous Cell Carcinoma of the Stomach: A Case Report and Review of the Literature. AB - Primary gastric squamous cell carcinoma (PGSCC) is an exceedingly rare disease, accounting for 0.04% - 0.07% of all gastric cancers. First reported in 1895 by Rorig et al, less than 100 cases of PGSCC worldwide have been reported in the literature. These reports show PGSCC is more common in males (5:1 male to female ratio), and exhibits a peak incidence in the sixth decade of life. It may involve any portion of the stomach with predilection for the proximal stomach, especially along the lesser curvature. Although no clear pathogenesis of this tumor has been reported, several plausible theories have been proposed. These include squamous differentiation of preexisting gastric adenocarcinoma, cancerization of ectopic squamous epithelium, malignant transformation of squamous metaplasia of glandular epithelium, association with Helicobacter pylori or Epstein-Barr virus infection, and evolution in the setting of marked chronic gastritis with intestinal metaplasia. This report presents and discusses the case of a 64-year-old female who developed PGSCC arising in the gastric fundus. PMID- 27265924 TI - Colon Ischemia After Weight-Loss Medication in a 36-Year-Old Woman. AB - Weight-loss medications have been associated with many conditions, including valvular heart disease, ischemic colitis, and pulmonary hypertension. There is a constant increase in the use of these drugs, especially new medications with better efficacy. Phentermine is one such drug, approved for short-term use to lose weight. We report a case of ischemic colitis in a female patient linked to inappropriate phentermine intake. The patient presented with symptoms of severe abdominal pain and repeated bowel movement associated with rectal bleeding for two weeks. Initial blood work was unremarkable for infectious and inflammatory causes. A CT scan was performed which revealed findings of ischemic colitis extending from transverse to descending colon. A biopsy study confirmed the same. Upon further questioning, the patient admitted to taking 37.5 mg of phentermine for two years beyond her prescribed period of 12 weeks. Hence, we propose that inappropriate use of phentermine caused ischemic colitis. With the widespread use of these medications, there is a need for heightened awareness among clinicians regarding adverse effects of phentermine. PMID- 27265925 TI - Splenic Injury and Hemoperitoneum as a Complication of Colonoscopy: A Case Report and Literature Review. AB - Colonoscopy rarely results in serious or life-threatening complications. While bleeding, perforation, and cardiorespiratory complications account for a majority of procedural-related complications, splenic injury and resulting hemoperitoneum remain a serious, potentially life-threatening adverse event. Splenic injury is an underreported and underappreciated complication of colonoscopy. In this case, a 71-year-old female presented one day after colonoscopy with splenic injury and hemoperitoneum as a complication of the recent colonoscopy. In addition to reviewing the literature, the case describes systems for grading splenic injury and the use of splenic artery embolization for controlling the bleed. Given the frequent use of colonoscopy as both a screening and therapeutic modality, it is pivotal for the general internist to be familiar with potential complications. Along with this broad sense of potential complications, it is important to use clinical acumen, clinical examination findings, and elicited history to select the imaging modality of choice in a timely manner. PMID- 27265927 TI - An Uncommon Complication of Esophageal Cancer. AB - Esophageal cancer is one of the rarer solid tumors that metastasize to the central nervous system. We describe a case of a 57-year-old male, previously confirmed to have obstructive esophageal adenocarcinoma with local mediastinal and esophagogastric lymph node involvement undergoing chemotherapy, who presented with altered mental status, headache, nausea, 15-pound weight loss, and neck stiffness. Prior staging with an MRI of the brain and spine was unrevealing, but a lumbar puncture demonstrated adenocarcinomatous spread to the cerebrospinal fluid, consistent with leptomeningeal carcinomatosis. PMID- 27265926 TI - Fixed Drug Eruption Late in the Course of Capecitabine Therapy. AB - A fixed drug eruption (FDE) is a toxic skin effect thought to be caused by delayed cell-mediated hypersensitivity to a pharmaceutical agent. We report herein the first known patient with capecitabine-induced FDE that appeared relatively late in the course of adjuvant therapy for rectal cancer. The temporal association with capecitabine use and prompt disappearance after capecitabine discontinuation make this relationship probable. Knowledge about this dermatologic skin effect seen with oral fluoropyrimidines should avoid unnecessary diagnostic workup and provide the necessary patient reassurance. PMID- 27265928 TI - Educational Intervention Along With Standardization of Diabetes Care Increased Inpatient HbA(1c) Testing: A Pilot Program. AB - OBJECTIVE: To continuously improve safe coordination of diabetes care throughout the hospital by ongoing implementation of standardized, hospital-wide staff education, and glucose management policies/protocols. METHODS: In December 2013, a hospital-wide multidisciplinary task force was formed to standardize the care for all patients being admitted to Saint Francis Hospital and Medical Center with the diagnosis of diabetes. The purpose of this team was to help develop policies and procedures on glucose management and educate staff on the current clinical practice guidelines. Prior to creating system-wide changes, the team decided to pilot the project on two units. RESULTS: A total of 144 patients with a primary or secondary diagnosis of diabetes were admitted to these two units between June 1 and July 31, 2014. The study group was found to have anincreaseinthe percentage of HbA(1c) tests (P < .01) being done when compared with 1173 patients in the rest of hospital. As a result of staff education, there was a decrease in hypoglycemia events (P = .05), and hyperglycemia events (P < .01) in the study group immediately following education; however during the follow-up period, the rate of hypoglycemic events was unchanged in both groups. CONCLUSION: Standardization of inpatient diabetes management with staff and patient education increased the testing of HbA(1c) in hospitalized patients and has potential to improve quality of care and patient safety. PMID- 27265929 TI - The Hartford Consensus IV: A Call for Increased National Resilience. AB - Despite advances in the response to active shooter and intentional mass casualty events, a gap remains in our national preparedness and resilience. Drawing from experiences at myriad mass casualty events, the immediate responder (volunteer responder) represents an underutilized resource, yet one capable of dramatically increasing our all-hazards (injuries from all natural and man-made causes) national resilience. The overarching principle of the Hartford Consensus, outlined in previous reports, is that no one should die from uncontrolled bleeding. We have championed the following acronym to summarize what we have determined are appropriate steps to ensure that the maximum number of victims of these tragic events can be saved: THREAT: Threat suppression. Hemorrhage control. Rapid Extrication to safety. Assessment by medical providers. Transport to definitive care. PMID- 27265930 TI - The Significance of a Finger. PMID- 27265931 TI - Population Health and the Practicing Physician. PMID- 27265933 TI - Is Health Insurance Illusory? PMID- 27265932 TI - Armed Only with Knowledge and a Belief in Medicine. PMID- 27265934 TI - If Socrates were a Physician. PMID- 27265935 TI - Not Available. PMID- 27265936 TI - [Adaptation potential of cardio-respiratory system in dust diseases]. AB - The article covers results of cardio-respiratory system evaluation in workers exposed to dust, on basis of adaptation potential evaluation via calculation of functional changes index and 6 minutes' walk test with continuous assessment of blood oxygenation and heart rate. Adaptation disorders are supported by results of external respiration assessment and echo-cardiography. PMID- 27265937 TI - [Features of nano aerosols action and safety measures]. AB - The article presents results of studies concerning influence of high-dispersed aerosol formed in traditional plasma processes on operators' health. Consideration also includes new technologies to obtain metall-containing nanoproducts; the authors recommend protection measures for workers, methods and devices to control nano aerosols in air. PMID- 27265938 TI - [Biomonitoring in workers exposed to pesticides: development and application of method detecting imidacloprid in urine]. AB - Imidacloprid is a relatively new insecticide in neonicotinoids chemical class with neuroactivity in insects, being one of the most widely used insecticides in the world. For biomonitoring in workers exposed to pesticides, the authors designed a method detecting low levels of Imidacloprid in urine of operators, based on tandem liquid mass-spectrometry with ionization source--electrostatic dispersion (positive ionization) in multi-reaction monitoring regime with subsidiary ion (mass/charge) 209 for quantitative assessment and ion 175.1 for confirmation onion ratio. The study incorporated diurnal urine, about 100 ml of average sample was frozen and kept at temperature -20C for analysis. Before extraction, the sample was unfrozen, an aliquot of 5 ml was selected, diluted with 5 ml of 0.1% formic acid. The substance was concentrated out of the urine samples via solid-phase extraction with application of cartridges based on octadecylsilane, eluition--1 ml of methanol. Lower limit of Imidacloprid detection in urine is 0.02 ng/ml, of the quantitative assessment--0.1 ng/ ml, linear range of concentrations measured 0.1-10 ng/ml. The method was tested for monitoring in workers exposed to Imidacloprid preparations in natural conditions of pesticides application in agriculture, with various processing technologies. Imidacloprid was identified in urine of two professional operators after work in seed treatment and the subsequent seeding at lower limit of detection (0.02 ng/ml) and 0.34 ng/ml. PMID- 27265939 TI - [Minimizing risk for health in workers engaged into preplanting treatment of planting material]. AB - Application of modern technologies and pesticides for preplanting treatment of planting material guarantees minimal risk of hazardous influence on workers with strict compliance with technologic regulations (preparation and working solution consumption, normalized technique, etc) and safety requirements (usage of recommended individual protection means, timely cleansing of equipment, etc). PMID- 27265940 TI - [Providing studies quality for pesticides risk evaluation in their use according to proper laboratory practice rules]. AB - The article covers experience of proper laboratory practice in hygienic studies examining air and workers' skin for assessment of exposure levels of pesticides in natural conditions of agricultural production. PMID- 27265942 TI - [Criterial value of oxidative stress parameters in exposure to vibration]. AB - The article covers results of study concerning metabolic processes in workers exposed to vibration. Findings are lipid peroxidation processes activation, depressed anti-oxidant system, changes in intracellular exchange processes, dependence of the studied parameters change on length of service with vibration exposure. PMID- 27265941 TI - [Influence of psychologic attitude to efficiency of pain treatment in vibration disease]. AB - The article presents results of study concerning influence of desadaptive psychologic attitudes on formation and perception of pain syndrome in 148 vibration disease patients. The authors determined clinical and psychologic predictors of efficiency of pain syndrome treatment in vibration disease patients. PMID- 27265943 TI - [Preventing cardiovascular risk in miners]. AB - The article presents results concerning usage of intravenous laser radiation of blood in miners with cardiovascular diseases. After cardiovascular state assessment, the miners at high cardiovascular risk were subjected to prophylactic procedures with traditional medical treatment added by intravenous laser therapy. Findings are anti-arrhythmic, antihypertensive, antiatherogenic and anti aggregation effects of complex treatment with intravenous laser radiation of blood in miners at high cardiovascular risk and its subsequent decrease due to treatment. PMID- 27265944 TI - [FEDERAL CLINICAL RECOMMENDATIONS IN DIAGNOSIS, TREATMENT AND PREVENTION OF HEARING LOSS DUE TO NOISE]. AB - Noise induced hearing loss is a slowly developing hearing impairment, caused by occupational exposure to excessive noise levels, constitutes a lesion of the auditory analyzer and clinically manifested as chronic bilateral sensorineural hearing loss. Currently, there is not a treatment that provide a cure of sensorineural hearing loss. Regular, individually tailored treatment should be directed to the pathogenic mechanisms and specific clinical symptoms of hearing loss, as well as the prevention of complications. We recommend using non-drug therapies that can improve blood flow in labyrinth, tissue and cellular metabolism. PMID- 27265945 TI - What's a Nurse's Value? Making Cents of Care. PMID- 27265946 TI - Effective Staffing Takes a Village: Creating the Staffing Ecosystem. AB - The traditional approaches to staffing and scheduling are often ineffective in assuring sufficient budgeting and deployment of staff to assure the right nurse at the right time for the right cost. As hospital merger activity increases, this exercise is further complicated by the need to rationalize staffing across multiple enterprises and standardize systems and processes. This Midwest hospital system successfully optimized staffing at the unit and enterprise levels by utilizing operations research methodologies. Savings were reinvested to improve staffing models which provided sufficient nonproductive coverage and patient driven ratios. Over/under-staffing was eliminated in support of the system's recognition that adequate resource planning and deployment are critical to the culture of safety. PMID- 27265947 TI - Nursing Management Minimum Data Set: Cost-Effective Tool To Demonstrate the Value of Nurse Staffing in the Big Data Science Era. AB - There is a growing body of evidence of the relationship of nurse staffing to patient, nurse, and financial outcomes. With the advent of big data science and developing big data analytics in nursing, data science with the reuse of big data is emerging as a timely and cost-effective approach to demonstrate nursing value. The Nursing Management Minimum Date Set (NMMDS) provides standard administrative data elements, definitions, and codes to measure the context where care is delivered and, consequently, the value of nursing. The integration of the NMMDS elements in the current health system provides evidence for nursing leaders to measure and manage decisions, leading to better patient, staffing, and financial outcomes. It also enables the reuse of data for clinical scholarship and research. PMID- 27265948 TI - Cost Effective Staffing for an EHR Implementation. AB - This case study explores costs of electronic health record (EHR) implementation with the nursing super-user role in a metropolitan, not-for-profit health care system. Tapping the local pool of unemployed newly graduated nurses as half the required super-user workforce leveraged the technology skills of novice registered nurses (RNs) as trainers of experienced nurses in five hospitals. The novel workforce migrated from hospital to hospital, thereby reducing the number of experienced nurses reassigned to super-user duties in each hospital. This strategy reduced the amount of contract labor required to backfill nurse super users' clinical shifts. Employment of the recently graduated nurses as RN residents upon completion of the EHR implementation enabled the organization to augment its clinical workforce with expert users of its EHR. The proposed innovative model increases super-users, minimizes disruption of core staffing, and dramatically reduces expense. PMID- 27265949 TI - Shifting the Curve: An Interview with David C. Benton. PMID- 27265951 TI - Searching for the Holy Grail of Care Delivery Models. AB - Too often health care executives state the need for more research, knowledge, and information in staffing. Perhaps what we really need is education and support for innovation in operations. In looking for the holy grail of staffing solutions, focused attention will need to be placed on creating innovative care delivery models. Leaders who are tasked with developing innovative care delivery models must have a supportive environment and given time to be successful. PMID- 27265950 TI - Staff Efficiency Trends Among Pediatric Hospices, 2002-2011. AB - This study provided the first examination of staff efficiency trends among pediatric hospices. Although pediatric staff efficiency demonstrated large variability from 2002 to 2011, the general trend in efficiency from 2003 to 2010. The decline in efficiency means, on average, pediatric hospices had higher operating expenses and used more capacity, but greater amounts of these greater outputs as measured by visits per patient. The study also highlights the crucial role pediatric hospice nurse managers play in developing effective workforce strategies that allow for responsive changes to workload fluctuations. Due to the associations between efficiency, regulation, and growth, nurse leaders' abilities to develop effective strategies are more imperative than ever to ensure quality end-of-life care for children and their families. PMID- 27265952 TI - Ambulatory Care Nurse-Sensitive Indicators Series: Capturing the Role of Nursing in Ambulatory Care--The Case for Meaningful Nurse-Sensitive Measurement. AB - The nation has been on a quest to advance quality in providing health care services and improving patient outcomes. The challenge has been to identify and define metrics that will demonstrate improvement. Acute care settings have a fairly well-established system of quality measurement, but ambulatory care systems are in less-developed stages. Imperative to accurate quality measurement in ambulatory care is to identify and define metrics that reflect the value of registered nurses to improved patient care and outcomes as well as to the organization. The American Academy of Ambulatory Care Nursing (AAACN) established a task force to determine appropriate measures of nursing quality. The task force spent 2 years investigating measures and produced an Industry Report that addresses measures of nursing quality. This article is the first in a series of articles that will reveal and discuss the contents of the Industry Report. PMID- 27265953 TI - A Brief Economic Analysis of the Looming Nursing Shortage In the United States. AB - The United States is projected to experience a nursing shortage in the coming years as market forces begin to shift away from equilibrium. A return to pre recession work levels, aging baby boomers, and insufficient numbers of nursing graduates adversely affect the supply of nurses The aging population, a rise in chronic care management needs, and the Affordable Care Act will result in an increasing demand for them. Returning to a state of equilibrium is critical if our health care system is to ensure care that is accessible, safe, and cost effective. PMID- 27265955 TI - While We Were Not Looking.... PMID- 27265954 TI - Windows to the Future: Can the United Nations Sustainable Development Goals Provide Opportunities for Nursing? AB - Windows of opportunity are wide open for the nursing profession to actively participate and engage in the policy implementation, evaluation, and achievement of the United Nations Sustainable Development Goals. Nurses bring valuable perspectives as members of diverse governance structures and offer a range of solutions that can help governments pursue and achieve the Sustainable Development Goals and targets by 2030. PMID- 27265956 TI - President's Page. PMID- 27265957 TI - Clinical Question: In adult patients on warfarin, does-home-self-testing of prothrombin time and/or international normalized ratio provide the same outcomes compared to testing by a home health nurse or in a clinical setting? PMID- 27265958 TI - Prescription Drug Misuse and Associated Risk Behaviors among Public High School Students in Oklahoma: Data from the 2013 Oklahoma Youth Risk Behavior Survey. AB - PURPOSE: The purpose of this study was to assess the magnitude of prescription drug misuse among Oklahoma high school students, examine associated risk factors, and inform state-based prevention strategies. METHODS: Data from the 2013 Oklahoma Youth Risk Behavior Survey were used for this analysis and were representative of public school students in grades 9 through 12 in Oklahoma. Variables were examined using percentages and 95% confidence intervals. The chi square test was used to test for differences in proportions. Logistic regression was used to produce adjusted odds ratios as measures of association between selected independent variables and prescription drug misuse. RESULTS: Nearly one in five students had ever used a prescription drug without a doctor's prescription. While there was no statistically significant difference of prescription drug misuse by gender or grade in the bivariate analysis, after covariate adjustment, females were 1.5 times more likely than males to have misused prescription drugs and twelfth graders were 1.7 times more likely than ninth graders to have misused prescription drugs. CONCLUSION: Students who had ever taken prescription drugs without a doctor's prescription were significantly more likely than students who had never taken prescription drugs without a doctor's prescription to have engaged in current tobacco use, current binge drinking, current marijuana use, and lifetime drug use and have a higher prevalence of suicide risk. PMID- 27265959 TI - Drug monitoring programs help patients and dentists. PMID- 27265960 TI - 3M Intraoral Impression Syringe. PMID- 27265961 TI - Payers Sued Over Coverage Of Expensive Hepatitis C Drugs. PMID- 27265963 TI - 'Mr. Watson-Come Here' A New Way to Share Data. PMID- 27265962 TI - MARKER MAGIC. PMID- 27265964 TI - Health Insurers Struggle to Manage Number, Cost of Genetic Tests. PMID- 27265965 TI - Drug Companies Ask Plans To Just Say 'Yes' to Risk. PMID- 27265966 TI - Making Treatment 'Sticky'. PMID- 27265967 TI - Cap on, Premiums up. PMID- 27265968 TI - A CONVERSATION WITH STEVEN PEARSON, MD. The Value of Drugs: It Is Not About the Money! PMID- 27265969 TI - Biosimilar Research Proceeds in Cancer, RA, and Hep B. PMID- 27265970 TI - Cancer Groups Give Part B Plan an F. PMID- 27265971 TI - Commentary on Current Trends in Rising Drug Costs and Reimbursement Below Cost. AB - PURPOSE: To quantify prescription drug price increases over a span of 3 years (2012-2015), as well as extrapolate current reimbursement rates expected by independent retail pharmacies. In addition, we investigate potential reasons for these increasing drug costs. DESIGN: Descriptive analysis. METHODOLOGY: National average drug acquisition costs (NADAC) data published by the Centers for Medicare & Medicaid Services were examined. Specifically, December 2012, 2013, and 2014, and July 2015 NADAC files were analyzed to identify generic and branded products with the highest percentage price increases. Percentage price differences were also calculated for 17 first-in-class drugs and their "me-too" competitors. The margin and margin percentage were calculated for claims adjudicated through four major payers. RESULTS: The top 50 generic drug price increases ranged from 474% to over 18,000% from December 2012 to July 2015. The top 50 branded drug price increases ranged from 63% to 391% during the same time period. The percentage price difference for the first-in-class drugs versus their me-too analogues ranged from -2.3% to 61,259%. The margin for generic drug claims adjudicated ranged from -$237.11 to-$1,105.96. The margin for branded drug claims adjudicated ranged from $272.42 to $360.17. CONCLUSION: Several potential reasons for the surge in prescription drug prices include manufacturer competition, industry consolidation, and capitalization on me-too drugs. This increase has compelled PBMs, health plan sponsors, and retail pharmacies to find novel ways to turn a profit, often at the expense of the consumer. Although there are no immediate solutions, legislation regulating PBM functions and the use of therapeutic interchange programs may offer health plans some assistance in managing drug costs. PMID- 27265972 TI - Top pharmacists see rising prices, doubt fast takeoff for other trends. PMID- 27265973 TI - A Light for Dark Places: Mental Wellness in Dental School. PMID- 27265974 TI - NSAIDS Unsafe for Many Patients. PMID- 27265975 TI - Drs. Dionne and Gordon Respond. PMID- 27265976 TI - Are Physicians Really That Unethical? PMID- 27265977 TI - Advancing Measurement and Quality Improvement in Dentistry. PMID- 27265978 TI - Quality Improvement Efforts in Pediatric Oral Health. AB - Quality improvement (QI) and measurement are increasingly used in health care to improve patient care and outcomes. Despite current barriers in oral health measurement, there are nascent QI and measurement efforts emerging. This paper describes the role that QI and measurement can play in improving oral health care delivery in clinical practice by presenting a QI initiative that aimed to test and implement a chronic disease management approach to address early childhood caries. PMID- 27265979 TI - Dental Quality Measurement--A Practitioner Perspective. AB - This article reviews the HealthPartners Dental Group's experience with clinical quality measurement and provides information on the administrative infrastructure that supports measurement within the group. Some examples of the role measurement plays in operations and clinical practice are also reviewed. PMID- 27265980 TI - Leading the Dental Quality Movement: A Dental Quality Alliance Perspective. AB - Changing regulatory priorities set forth by the Affordable Care Act and recent activities of the Centers for Medicare and Medicaid Services clearly prioritize the need to improve the quality of health care in both the public and private sectors. As the largest multistakeholder organization focused on oral health care quality measurement and improvement, the Dental Quality Alliance is leading the way in establishing standardized and valid quality measures applicable in both private and public sectors. PMID- 27265982 TI - Using Patient Images to Promote Your Practice. PMID- 27265981 TI - Growth Trends in Dental Service Organizations. AB - There are a number of factors fueling the growth of large group practices managed by corporations across the U.S., including California. These evolving trends are shaping the dental profession and practice models in a variety of ways. PMID- 27265983 TI - Sales and Use Tax. PMID- 27265984 TI - The evolution of scuba divers pulmonary edema: an editorial perspective. PMID- 27265985 TI - The evolution of scuba divers pulmonary edema. AB - The evolution of scuba divers pulmonary edema is described. When discovered in 1981, it was believed to be a cold-induced response in a submerged, otherwise healthy, scuba diver. The clinical features are described and discussed, as are the demographics. An alleged prevalence of 1.1% was complicated by problematic statistics and an apparent increase in reported cases. Recurrences both while diving and swimming or snorkeling were common. More recent case reports and surveys are described, identifying predisposing factors and associations, including cardiac pathology. Stress cardiomyopathies, reversible myocardial disorder or Takotsubo cardiomyopathy, may complicate the presentation, especially in older females. Relevant cardiac investigations and autopsy findings are reviewed. Disease severity and potential lethality of scuba divers pulmonary edema became more apparent early this century, and these influence our current recommendations to survivors. First aid and treatment are also discussed. PMID- 27265986 TI - Brief communication: Self-reported health and activity habits and attitudes in saturation divers. AB - INTRODUCTION: Exposure to the confined hyperbaric, hyperoxic environment of the saturation chamber poses a number of unique physiological challenges to divers. Appropriately tailored training, nutrition and health programs may help support the body to cope with and overcome these challenges. AIM: To describe the self reported habits and attitudes of saturation divers toward issues related to health, lifestyle, nutrition and physical activity. METHODS: A questionnaire was developed to elicit information related to four key areas: 1) respondent demographics; 2) physical activity habits and attitudes; 3) nutritional attitudes; and 4) general lifestyle and health information. RESULTS: Respondents (n = 89/45%) reported a generally healthy lifestyle, including high physical activity levels while onshore, low tobacco use and alcohol intakes within U.K. recommended guidelines. Responses to in-chamber items demonstrated reduced physical activity, disrupted sleep and distorted taste and smell perception. In addition, lethargy, headaches and musculoskeletal stiffness/soreness were reported as frequent symptoms following a period of time spent in saturation. CONCLUSIONS: Results of this study provide an in-sight into the self-reported practices and attitudes of saturation divers and appear to indicate a generally healthy lifestyle in the respondents. Some themes emerged which may impact on diver health and performance while in saturation. The results of this report may help provide a platform to generate hypotheses for further research and facilitate development of appropriately tailored nutrition and training-based strategies for saturation divers. PMID- 27265987 TI - Echocardiographic evaluation of intracardiac venous gas emboli following in-water recompression. AB - Decompression sickness is a potentially fatal illness. Optimal treatment is dry recompression with hyperbaric oxygen. In-water recompression (IWR) offers expedited treatment but has insufficient evidence to recommend it as a treatment option. This trial compares IWR to standard surface oxygen treatment using 2D echocardiography as the semi-quantitative measurement for inert gas loading. Divers were randomly assigned to either IWR or normobaric oxygen (NBO2). A provocative dive profile to 33.5 meters for 25 minutes was used to stimulate bubble formation. After 60 minutes on the surface, bubble scoring was obtained using 2D echocardiography. Divers underwent either the IWR or NBO2 treatment for 82 minutes. Echocardiography was then repeated. Pre-treatment mean bubble counts were 28.1 bpf (bubbles per echo frame), [+/- 13.2 to 43.0 95% CI] for IWR, and 18.3 bpf [+/- 0.0 to 39.6 95% CI] for NBO2. After treatment, mean bubble score dropped to 0.1 bpf [+/- 0.0 to 0.2 95% CI] (p < 0.01) and 1.8 bpf [0.0 to 3.8 95% CI] (p = 0.103) respectively. IWR vs. NBO2 reduction of bubble counts was 99.7% vs. 90.1%; however, this was not found to be statistically significant. IWR reduced the central VGE load compared to NBO2, suggesting that IWR is a viable emergency treatment when a recompression chamber is unavailable. PMID- 27265988 TI - The safety of hyperbaric oxygen treatment--retrospective analysis in 2,334 patients. AB - INTRODUCTION: Hyperbaric oxygen (HBO2) therapy is applied in a growing number of cases for patients with different comorbidities and is considered a generally safe therapy. The main side effects related to HBO2 therapy are barotrauma, central nervous system- and pulmonary oxygen toxicity, claustrophobia, anxiety and visual disturbances. The aim of this study was to evaluate the incidence of side effects associated with HBO2 therapy and risk factors in a large cohort of patients treated for different indications. METHODS: We conducted a retrospective analysis of 2,334 patients treated in the Sagol Center of Hyperbaric Medicine and Research, Assaf Harofeh, Israel, between June 2010 and December 2014. Patients were classified to one of three categories of indications: Category A--non neurological indications; Category B--neurotherapeutic indications; and Category C--acute indications. RESULTS: From a total of 2,334 patients, 406 (17.4%) experienced adverse event(s) (one or more) during HBO2 therapy sessions. The overall per-session incidence was 721:100,000 events:sessions (0.72%). The main complication was middle ear barotrauma, which occurred in 9.2% of patients and in 0.04% of sessions. Females and children under the age of 16 years had increased risk for barotrauma. Other complications--hypoglycemia, oxygen toxicity, dizziness, anxiety reactions, dyspnea and chest pain--occurred in 0.5-1.5% of patients. CONCLUSIONS: Strict operational protocols, including pre-HBO2 therapy evaluations and in-chamber monitoring, are essential and improve patient safety. When applied, HBO2 therapy can be considered one of the safest medical treatments available today. PMID- 27265989 TI - Changes in vasomotion--effect of hyperbaric oxygen in patients with diabetes Type 2. AB - OBJECTIVES: To investigate vasomotion in diabetic patients who underwent sessions of hyperbaric oxygen (HBO2) therapy. MATERIALS AND METHODS: Seventy-one patients with diabetes Type 2 and lower-extremity neuropathy were enrolled in a prospective matched case-control study. A total of 39 patients underwent 15 sessions of HBO2 therapy consisting of 90 minutes of breathing 100% oxygen at 2.5 atmospheres; 32 were included in the control group without exposure to hyperbaric oxygen. We used laser Doppler flowmetry for measurement of flowmotion. Spectral analysis of laser Doppler flowmetry signals was performed using the Fast Fourier transform algorithm. The total spectral activity was divided into the subgroup of endothelium, adrenergic, intrinsic smooth muscle, respiratory and cardiac spectral activity. The lateral ankle and the dorsum of the foot were chosen for this study. Heating provocation test was performed on both sites. The measurement was performed 24 hours before the first HBO2 session and 24 hours after the last (15th) session of therapy. RESULTS: We observed a significant increase in respiratory, cardiac and total spectral activity of flowmotion on the ankle as well as a significant increase in cardiac and total spectral activity on the dorsum of the foot in patients without a foot ulcer. In the subgroup of patients with a diabetic ulcer, a decrease of total spectral activity of flowmotion on the dorsum of the foot was observed. CONCLUSION: Flowmotion (indirectly vasomotion) measured by laser Doppler flowmetry changed significantly after HBO2 therapy. Flowmotion dynamics may partly explain the positive effect of HBO2 on the healing process of a diabetic ulcer. PMID- 27265990 TI - The facilitatory effects of hyperbaric oxygen treatment on membrane bone wound healing in a rat calvarial defect model. AB - We examined the effect of hyperbaric oxygen (HBO2) treatment on bone wound healing in a rat calvarial defect. Critical-sized defects were created in the calvaria of adult Wistar rats. The animals were divided into four groups--HBO2, normobaric oxygen, hyperbaric air, and no treatment. Treatments were performed five days a week, for two weeks. Micro-computerized tomography and histological analysis were used to evaluate the bone defects. Regenerated bone areas were calculated as the percentage of new bone in the cross-sectional area of defect. The new bone cross-sectional area was significantly greater in the HBO2 group than in the other groups. There were no significant differences in the numbers of nucleated cells in the new bone areas. Although new bone volume per defect volume was significantly greater in the HBO2 group than in the other groups, no significant differences in bone mineral density in the new bone area were observed. These findings indicate the facilitatory role of HBO2 treatment on bone wound healing in the rat calvarial bone defect, and it does not appear to have any negative effects on bone maturity. We propose that HBO2 treatment would be useful in promoting bone regeneration following injury in the orofacial region. PMID- 27265991 TI - The effect of environmental pressure and resin cements on the push-out bond strength of a quartz fiber post to teeth root canals. AB - AIM: To evaluate the effect of environmental pressure changes on the bond strength between a fiber post and one of three resin cements using different mixing methods and modes of application. METHODOLOGY: Sixty single-canal human teeth were divided into three groups (n = 20) and endodontically treated. Post spaces were prepared, and a quartz fiber post was secured with either a self adhesive machine-mixed cement (RelyX Unicem, Aplicap), a self-adhesive hand-mixed cement (RelyX Unicem), or a self-etching dual-cured resin cement (Panavia F2). Half of each group was subjected to 24 pressure cycles from 0 to 5 atmospheres. The mean push-out bond strength of the posts was calculated and statistically analyzed using ANOVA and Tukey tests (alpha = 0.05). RESULTS: Regardless of the pressure, Unicem Aplicap achieved the highest bond strength (P < 0.05). The bond strengths of all groups were significantly lower after they were subjected to the pressure cycles (P < 0.003), and they were lower in the apical regions. CONCLUSION: Bond strengths between the fiber post and root canal can be affected by environmental pressure while the type of resin cements, their mixing methods and modes of application incorporated lower porosity, achieving higher bond strength. PMID- 27265992 TI - Hyperbaric oxygen therapy in sudden sensorineural hearing loss following spinal anesthesia: case reports. AB - The management of sudden sensorineural hearing loss following spinal anesthesia is currently an open problem. Several strategies have been used with variable results and, to the best of our knowledge, there are no prior accounts in the literature on the use of hyperbaric oxygen therapy in the treatment of this complication. We report two cases of acute onset of unilateral hearing loss after spinal anesthesia, with significantly improved results after hyperbaric oxygen therapy. A hypothesis on the possible mechanism behind this complication is discussed. A relation is established between hyperbaric oxygen therapy and this hypothetical mechanism, in order to explain successful results in the reported cases. PMID- 27265993 TI - Complete recovery following hyperbaric oxygen therapy in idiopathic sudden sensorineural hearing loss--a report of two cases. AB - Idiopathic sudden sensorineural hearing loss (ISSHL), a common otologic emergency, presents mostly as an abrupt onset unilateral hearing loss, aural fullness, often with vertigo and tinnitus, usually upon awakening in the morning. Its etiopathogenesis is multifactorial, so a number of different therapeutic regimens are in practice, hyperbaric oxygen (HBO2) therapy being an effective yet underutilized one. Not all cases recover completely even after treatment. Here we describe two cases of ISSHL, diagnosed on the basis of clinical examination and pure-tone audiometry, who had a complete recovery following administration of HBO2 therapy in addition to medical treatment. These cases are reported to highlight the effectiveness of this modality in a physician's armamentarium. PMID- 27265994 TI - Bilateral non-arteritic ischemic optic neuropathy treated with HBO2 therapy: A case report of angiographic and electrodiagnostic findings. AB - INTRODUCTION: Non-arteritic anterior ischemic optic neuropathy (NAION) is one of the most widespread visually disabling diseases in the middle-aged and elderly population. It typically presents as acute painless unilateral vision loss in patients over 50 years of age. The fellow eye of NAION patients is often sequentially affected. Involvement of the second eye occurs within three years in approximately 45%-50% of patients. Currently there is no generally accepted treatment for NAION but a number of medical and surgical therapies have been proposed. REPORT OF A CASE: This is a case of non-contemporary bilateral non arteritic anterior ischemic optic neuropathy (NAION) in a 66-year old woman treated with hyperbaric oxygen (HBO2) therapy after ineffective systemic corticosteroid therapy. Visual acuity (VA), visual evoked potentials (VEP) findings, perimetric examination results and angiographic images were recorded and analyzed before and after hyperbaric oxygen treatment. DISCUSSION: After several months from the optic nerve vascular injury, VA, VEP values, perimetric examination results and angiographic images revealed a very important recovery. These results maintained stable during the follow-up at about nine months. HBO2 therapy has been revealed to be a safe and efficacious adjunctive therapy, even after many months after the injury. While this case is promising, double-blind randomized controlled trials will be necessary to prove the efficacy of HBO2 in the treatment of NAION. PMID- 27265995 TI - Ischemic colitis associated with acute carbon monoxide poisoning--a case report. AB - Carbon monoxide (CO) poisoning is common, but it has rarely been reported to cause ischemic colitis. In this case, a 34-year-old female with depression presented to an emergency department after a period of unconsciousness, with urinary and bowel incontinence, following exposure to car exhaust. Her carboxyhemoglobin level was 23%. She had metabolic acidosis. She was transferred to our facility for hyperbaric oxygen treatment, where she had intractable nausea/vomiting with abdominal pain and bright-red bleeding per rectum. She exhibited lower abdominal tenderness and hypoactive bowel sounds. Vital signs were: temperature 36.8 degrees C; blood pressure 137/ 86 mmHg; heart rate 114 beats/minute; respiratory rate 28 breaths/minute. The patient's electrocardiogram showed sinus tachycardia with T-wave inversions in leads I, aVL and V3-V6. The troponin I level peaked at 3.7 ng/ml. Echocardiogram showed a reduced ejection fraction of 30%-35%, with akinesis in the posterior lateral and distal anterior distributions. Computed tomography of the abdomen revealed diffuse colonic mural thickening, supporting mesenteric ischemia. Sigmoidoscopy showed edematous friable pale mucosa from rectum to distal sigmoid colon. Hyperbaric oxygen was deferred based on the patient's status. Over three days, the initial hematochezia progressed to melena and then resolved. Adenosine cardiac stress MRI was normal. She was transferred to the psychiatry service and discharged four days later. Four years later, she has no gastrointestinal, cardiac or cognitive problems. PMID- 27265996 TI - Cedars-Sinai Medical Center Audit Process Pinpoints Risks and Solutions. PMID- 27265997 TI - 501(r): The Clock Is Ticking. PMID- 27265998 TI - A 12-Month Plan for Coding Compliance. PMID- 27265999 TI - Sounding the alarm about suicide risk. AB - The Joint Commission (TJC) issued a Sentinel Event Alert, noting that in too many instances healthcare providers are not recognizing signs of suicide risk in patients who present for care. While the agency calls on all frontline providers to screen for suicide risk, experts note the issue is of particular importance to EDs because this is one of the most likely places for patients at high risk for suicide to present. Beyond identifying risk, experts note emergency providers and staff must receive training to effectively manage patients at risk for suicide. Further, TJC calls for the development of appropriate referral sources and mechanisms for follow-up contact. TJC reports that between 2010 and 2014, its Sentinel Event Database received 1,089 reports of suicides. The most common root cause was inadequate assessment. According to TJC, in 2014 more than 21% of accredited behavioral health organizations and 5% of accredited hospitals were non-compliant with conducting a risk assessment to identify patient characteristics or environmental factors related to suicide risk. Beyond instances of obvious risk, strong tipoffs that suicide is a concern include signs of hopelessness or evidence that the patient has no sense of the future. Further, experts note the strongest indicator of a future suicide attempt is a past attempt, so evidence in the record of a past suicide attempt, or a family history of suicide, should be taken very seriously. Researchers found that a three-item instrument, dubbed the Patient Safety Screener-3, can double the number of patients identified as at risk for suicide over usual care in a busy emergency setting. Experts recommend asking screening questions during the primary nursing assessment for most patients, and at triage for patients who present with a primary psychiatric complaint. Some experts suggest regionalizing mental health care, much like the country does with trauma care. However, communities must ensure they maintain adequate funding for such endeavors. PMID- 27266000 TI - New opioid prescribing guidelines favor non-opioid alternatives. AB - Determined to make a dent in the growing problem of opioid addiction, the CDC has unveiled new guidelines for opioid prescribing for chronic pain. The recommendations urge providers to be more judicious in their prescribing, opting for opioids only after carefully weighing substantial risks and benefits. Public health authorities note the rampant use and misuse of opioids have "blurred the lines" between prescription opioids and illicit opioids. The new guidelines are designed to help frontline providers balance the need to manage their patients' chronic pain with the duty to curb dangerous prescribing practices. The recommendations are built around three principles: favor non-opioid alternatives for most cases of chronic pain, use the lowest effective dose when prescribing opioids, and exercise caution/monitor patients who are treated with opioids. PMID- 27266001 TI - Fresh policies and procedures, transparency fuel ED turnaround. AB - The ED at Banner Payson Medical Center in Payson, AZ, has charted dramatic improvements on key metrics through a range of staff and policy changes. In just a few months, the ED has halved wait times, patient satisfaction has improved, and daily volume is up. Administrators say the secret to the success of the effort is a move to be transparent by posting key metrics regarding patient flow, a tactic that has helped the team pull together and feel a sense of accomplishment when performance goals are achieved. Administrators adjusted staff schedules to better match patient volume patterns in the ED, and they added staff to help nurses during peak hours. A new provider group enlisted the assistance of scribes during peak hours to manage the documentation workload while also enabling physicians to focus more patient interaction. Physicians hold end-of shift huddles to review successes and challenges, and to improve physician/nurse communication. The tactic also helps develop the staff from an educational standpoint. PMID- 27266002 TI - I.T. SOLVES THE PAYMENT PUZZLE. Providers deploy analytics, cost estimators as model changes. PMID- 27266003 TI - DOUBLE-TEAM DATA ANALYTICS. Allina Health boosts clinical operations with big data partner. PMID- 27266004 TI - PLUGGING AWAY AT LEAKAGE. ACOs use analytics, IT to manage out-of-network care. PMID- 27266005 TI - KEEPING MU GOING FOR RURALS. Lack of support, incentives hurt MU's staying power. PMID- 27266006 TI - GETTING VALUE FROM EHR DATA. Analytics push yields payoff at Medical Center Health. PMID- 27266007 TI - FHIR Man. PMID- 27266008 TI - Oral and Maxillofacial Pathology Case of the Month. Plexiform unicystic ameloblastoma with invasive mural component. PMID- 27266009 TI - Dentists and Populations in Underserved Areas of Texas. PMID- 27266010 TI - Five Year Clinical Survival Rate of Metal-Ceramic Single Crowns is Similar to All Ceramic Single Crowns (UT CAT #2983). PMID- 27266011 TI - AN INSTRUMENT SLIPS DOWN A PATIENT'S THROAT: A CASE STUDY. WHAT WENT WRONG? AND WHAT SHOULD HAVE BEEN DONE?. PMID- 27266012 TI - Co-Principal Investigators And Co-Directors: Benefits of a Scientific Copilot. PMID- 27266013 TI - Planning for the Future. PMID- 27266014 TI - How to Find More Hours in the Day. PMID- 27266015 TI - [The gastrulation in Cnidaria: A key to understanding phylogeny or the chaos of secondary modifications?]. AB - The data revealed by comparative embryology of the basal (diploblastic) metazoans is traditionally considered a valuable potential source of information on the origin and early evolution of the animal kingdom and its major clades. Special attention is paid to the fundamental morphogenetic process of gastrulation during which the cells of the early embryo differentiate into the germ layers and the primary body plan is formed. Comparative analysis of gastrulation in different cnidarian taxa reveals high level of intergroup, intragroup, and individual variation. With few exceptions, there is no robust correlation between the type of gastrulation and the taxon. Current data do not support the idea that morphogenetic processes underlying cnidarian gastrulation can be divided into several distinct types. Rather, there is a continuum of equifinal ontogenetic trajectories. In cnidarians, the mode of gastrulation apparently depends less on the macroevolutionary history of the species than on various evolutionary plastic features, such as the oocyte size, the amount of yolk, the number of cells at the blastula (or morula) stage, the presence of phototrophic symbionts, or the ecology of the larva. Thus, in cnidarians, morphogenetic basis of gastrulation contains only a very weak phylogenetic signal and can have only limited application in phylogenetic reconstructions. On the other hand, comparative studies of the ontogeny of the basal metazoans shed light on the general rules of the evolution of morphogenetic processes that is crucial for understanding the early history of the animal kingdom. PMID- 27266016 TI - [Local population of Eritrichium caucasicum as an object of mathematical modelling. I. Life cycle graph and a nonautonomous matrix model]. AB - For the plant species, which is considered a short-lived perennial, we have composed a scale of ontogenetic stages and the life cycle graph (LCG) according to annual observations on permanent sample plots in an Alpine lichen heath during the 2009-2014 period. The LCG that reflects seed reproduction has been reduced to the one that avoids the stage of soil seed bank, yet preserves the arcs of annual recruitment. The corresponding matrix model of stage-structured population dynamics has four stages: juvenile plants (including seedlings), virginal, generative, and 'terminally generative' (the plants die after seed production). Model calibration reduces to directly calculating the rates of transition between stages and those of delays within stages from the data of only one time step, while keeping the two reproduction rates uncertain, yet confined to the quantitative bounds of observed recruitment. This has enabled us to determine a feasible range for the dominant eigenvalue of the model matrix, i.e., the quantitative bounds for the measure of how the local population adapts to its environment, at each of the five time steps, resulting in aformally nonautonomous model. To obtain 'age-specific parameters' from a stage-classified model, we have applied the technique that constructs a virtual absorbing Markov chain and calculates its fundamental matrix. In a nonautonomous model, the estimates of life expectancy also depend on the time of observation (that fixes certain environmental conditions), and vary from two to nearly seven years. The estimates reveal how specifically short lives the short-lived perennial, while their range motivates the task to average the model matrices over the whole period of observation. The model indicates that Eritrichium caucasicum plants spend the most part of their life span in the virginal stage under each of the environment conditions observed, thus revealing the place retention strategy by C. K6rner (2003), or the delayed-development strategy by L.A. Zhukova (1995). We discuss the prospects of model experiments with a logically nonautonomous model to forecast the long-term dynamics of E. caucasicum under a scenario of climate changes. PMID- 27266017 TI - [Modeling of species distribution using topography and remote sensing data, with vascular plants of the Tukuringra Range low mountain belt (Zeya state Nature Reserve, Amur Region) as a case study]. AB - On the basis of maximum entropy method embedded in MaxEnt software, the cartographic models are designed for spatial distribution of 63 species of vascular plants inhabiting low mountain belt of the Tukuringra Range. Initial data for modeling were actual points of a species occurrence, data on remote sensing (multispectral space snapshots by Landsat), and a digital topographic model. It is found out that the structure of factors contributing to the model is related to species ecological amplitude. The distribution of stenotopic species is determined, mainly, by the topography, which thermal and humidity conditions of habitats are associated with. To the models for eurytopic species, variables formed on the basis of remote sensing contribute significantly, those variables encompassing the parameters of the soil-vegetable cover. In course of the obtained models analyzing, three principal groups of species are revealed that have similar distribution pattern. Species of the first group are restricted in their distribution by the slopes of the. River Zeya and River Giluy gorges. Species of the second group are associated with the southern macroslope of the range and with southern slopes of large rivers' valleys. The third group incorporates those species that are distributed over the whole territory under study. PMID- 27266018 TI - [A phylogenetic analysis of plant communities of Teberda Biosphere Reserve]. AB - Phylogenetic analysis of communities is based on the comparison of distances on the phylogenetic tree between species of a community under study and those distances in random samples taken out of local flora. It makes it possible to determine to what extent a community composition is formed by more closely related species (i.e., "clustered") or, on the opposite, it is more even and includes species that are less related with each other. The first case is usually interpreted as a result of strong influence caused by abiotic factors, due to which species with similar ecology, a priori more closely related, would remain: In the second case, biotic factors, such as competition, may come to the fore and lead to forming a community out of distant clades due to divergence of their ecological niches: The aim of this' study Was Ad explore the phylogenetic structure in communities of the northwestern Caucasus at two spatial scales - the scale of area from 4 to 100 m2 and the smaller scale within a community. The list of local flora of the alpine belt has been composed using the database of geobotanic descriptions carried out in Teberda Biosphere Reserve at true altitudes exceeding.1800 m. It includes 585 species of flowering plants belonging to 57 families. Basal groups of flowering plants are.not represented in the list. At the scale of communities of three classes, namely Thlaspietea rotundifolii - commumties formed on screes and pebbles, Calluno-Ulicetea - alpine meadow, and Mulgedio-Aconitetea subalpine meadows, have not demonstrated significant distinction of phylogenetic structure. At intra level, for alpine meadows the larger share of closely related species. (clustered community) is detected. Significantly clustered happen to be those communities developing on rocks (class Asplenietea trichomanis) and alpine (class Juncetea trifidi). At the same time, alpine lichen proved to have even phylogenetic structure at the small scale. Alpine (class Salicetea herbaceae) that develop under conditions of winter snow accumulation were more,even at the both.scale, i.e., contained more diverse and distantly related plant species compared with random samples. (Scheuchzerio Caricetea fuscae) aquatic communities in cold (Montio-Cardaminetea), sedge meadows (Carici rupestris-Kobresietea bellardii), and communities, in which shrubs and predominated (juniper and rhododendron elfin woods, class Loiseleurio Vaccinietea), have been studied only at the larger scale and showed significant evenness of species composition, i.e., were phylogenetically more diverse compared with random samples. PMID- 27266019 TI - [The response of forest ecosystems to reduction in industrial atmospheric emission in the Kola Subarctic]. AB - In spite of reduction in atmospheric emission, current state of forest ecosystems within the impact zone of Severonickel enterprise still reflects the entire spectrum of anthropogenic digression stages. As the distance to the enterprise grows shorter, structural-functional changes in forest communities are manifested in dropping out of mosses and lichens, replacement of undershrub by Poaceae, worsening of timber stand and undergrowth conditions and their progressive dying off, and, as a result, in forming of anthropogenic wastelands. Alterations of elemental composition of fir bark and needles due to exposure to pollutants consist in accumulation of nickel, copper, cobalt, arsenic, and sulfur along with depletion of calcium, magnesium, manganese, and zinc. According to the data obtained by correlation and multiparameter analyses, the accumulation of heavy metals in fir organs is closely related to the increasing of their concentration in root-inhabited soil layers as the distance to the pollution source is getting shorter. By comparison with the background fir grove, concentration of available compounds of nickel and copper in the ground litter of open fir-birch woodland near the enterprise increases by the factor of 30-60, reaching up 280 and 130 mg/kg respectively. With the increasing of anthropogenic stress, the ground litter becomes depleted of available calcium, magnesium, potassium, manganese, and zinc. For the first time, the coupled dynamics of vegetation and soil state in fir forests as a response to reduction in atmospheric emission is tracked back. The most distinguishable response to the reduction appears to be the development of small-leaved plants' young growth within the impact zone. For the last decade, concentration of nickel in fir needles and in ground litter has reduced by the factor of 1.2-2. As for copper, its concentration in needles has reduced by the factor of 2-4, though in ground litter remains the same. By comparison with the period of maximum emission at the edge of 1980-90s, in open fir-birch woodland near the enterprise the concentration of nickel and copper in needles has reduced by the factors of 2.5-6 and 7-12 respectively. This reduction of heavy metals concentration in fir needles is related mainly to diminishing of their emission from the atmosphere, although their stores, accumulated in soil during previous decades, still remain quite plentiful. PMID- 27266020 TI - [COMPLEX ASSESSMENT OF ENVIRONMENTAL FACTORS AND POSTVACCINAL IMMUNE STATE]. AB - This article was written on the base of the analysis of data of protocols of annual serological sturdies of the post-vaccination immunity status in indicator groups of populations, the analysis of samples of drinking water air and soil with the assessment of the socio-economic development of mono-towns and rural settlements. In the article there is reflected the comprehensive assessment of environmental factors and specific features of the formation of socio-economic conditions of rural communities and mono towns. There was performed a comparative assessment of the status of post-vaccination immunity to infections controlled by specific means of prevention, in different age groups in mono towns and rural settlements. There was established a dependence of the formation of post vaccination immunity on the state of environmental factors. PMID- 27266021 TI - [CHANGING OF PHYSICO-CHEMICAL PARAMETERS OF NON-CONTACT (ELECTROCHEMICAL) ACTIVATED DRINKING WATER IS ASSOCIATED WITH INDUCTION OF GENOMIC INSTABILITY OF CULTIVATED HUMAN BLOOD LYMPHOCYTES]. AB - In the article there are presented data which are the fragment of large multidisciplinary study of genetic safety of non-contact electrochemically activated water (NAW). The aim of this study was the analysis of the relation of impacts of genomic instability (micronucleus test with cytochalasin B) detected in human blood cells, cultured in medias prepared on the base of these NAWs, with physical and chemical properties of these NaWs. In experiments there were used catholytes and anolytes obtained by activation of osmotic, tap and dining bottled water As a result of such activation, all waters were shown to acquire the ability to induce genomic instability in cellular cultures. Notably in cell cultures on catholytes and anolytes these effects differed between themselves and have been associated with different physical and chemical properties of the NAWs. PMID- 27266022 TI - [FEATURES OF THE CONTENT OF DRINKING WATER IN THE CITY OF MAGADAN AND POPULATION HEALTH]. AB - By methods of atom-emission and mass spectrometry with inductively bonded argon plasma there was determined the content of 25 macro- and trace elements in tap cold drinking water used by the residents of the city of Magadan for food purposes and in hair samples of 30 young male Europeans aged of 17-23 years, who are the residents, of the city of Magadan. According to our data the content of 25 elements in drinking water conforms to standards, but that content of such essential elements as Co, Cr Cu, I, Mn, Na, Se, Zn is shown to be lower than referential indices. After boiling the water the concentration of trace elements is changed. The content of Cd, Cu, K, P Pb, Zn, Ni becomes lower significantly. In healthy young men aged of 17-23 years, from the number of natives Europeoids, residents of the North there was detected deficit of Co and I (86% and 62%, respectively), lower concentrations of Ca, Mg, Se, Zn (76%, 69%, 24%, 24%, respectively). The constant use by residents of the city of Magadan of ultrafresh brackish drinking water in food aims may be the one of the main reasons of the imbalance of macro- and micronutrients in the body, characterized by features of the so-called "northern" type with a marked deficiency of basic essential elements. PMID- 27266023 TI - [SANITARY DANGEROUS FILAMENTOUS MICROORGANISMS IN SOILS OF THE CITY OF VORONEZH]. AB - On the example of urban soils of the city of Voronezh there was revealed dependence of the degree of the disturbance of complexes of filamentous microorganisms on soil contamination levels. For the complex of micromycetes in the recreational area of the city disturbances are reversible and correspond to the adaptive range of "stress". In the transport an irreversible transition originates to the adaptive range of "resistance". There are accumulated toxigenic, opportunistic and allergenic fungi species that is harmful to the health of the urban population. The complex of soil actinomycetes is more sustainable. Microbiological indices (lists of indicative species of fungi) should be used for the monitoring of urban soils. PMID- 27266024 TI - [ASSESSMENT OF THE IODINE STATUS IN THE POPULATION IN WESTERN KAZAKHSTAN ACCORDING TO DATA OF URINARY IODINE CONCENTRATIONS]. AB - AIM: To evaluate iodine status in the population of Western Kazakhstan on the example oftheAktobe region according to data of urinary iodine concentrations. There were examined 2257 children aged from 7 to 12 years. Urinary iodine was carried out in 10% of schoolchildren by semiquantitative method under field conditions. According to the 30-cluster survey the prevalence of goiter in the region amounted to 42.71 +/- 1.04%. The proportion of children with optimal urinary iodine concentrations is only 12.8%, more than 300 mcg/l--57.82% of the children, more than 400 mcg/l was determined in 25.12% of the children. The high prevalence of goiter against the background of high rates of urinary iodine suggests the impact of other goitrogenic factors in the region. PMID- 27266025 TI - [ROLE OF GENETIC POLYMORPHISM AND DIFFERENCES IN THE DETOXIFICATION OF CHEMICAL SUBSTANCES IN THE HUMAN BODY]. AB - There are given modern views on the role of genetic polymorphism on the detoxification of chemical substances and individual sensitivity in workers to the development of diseases associated with xenobiotics metabolism disorders. In the search for genetic markers of occupationally caused diseases it is promising to study allelomorphs of genes responsible for the polyfunctional response of the human body, including genes involved in xenobiotic biotransformation. There is substantiated the expediency of compilation and introduction of genetic passports for stuff occupied at hazardous chemical enterprises. PMID- 27266026 TI - [IDENTIFICATION OF OCCUPATIONAL RISK FOR ARTERIAL HYPERTENSION. 1: ELIMINATION OF THE MODIFYNG INFLUENCE OF FACTORS OF CARDIOVASCULAR RISK]. AB - On results of research in 13 occupational groups (3842 workers, men) there were performed an analysis of a contribution of non-occupational factors of cardiovascular risk (FCVRs) and the elimination of their modifying influence on risks for the development of the arterial hypertension (AH). In the capacity of non-occupational FCVRs there were considered 16 predictors of AH. There were calculated the relative risk of AH and 95% the confidential interval (CI) in occupational groups on benchmark data of the prevalence rate of AH and after the elimination of the modifying influence of FCVRs. Reference group was the general sample, that is, all the occupations. Modifying influence of FCVR was eliminated by means of direct standardization. With the aid of trees of classifcation from the number of FCVRs in occupational groups the presence of obesity and age of the worker (respectively, 100 and 78 conditional points) was shown to have the maximum impact on the development of AH. Elimination of the influence of data of FCVRs led to the change of benchmark values of occupational risks of AH in the average for 10%, in four occupations level of the statistical importance of risks of AH changed. In top-managers, and also in operating personnel and technical workers the risk for AH from the high decreased to not significant, respectively to 1,00 at 95%, CI: 0.74-1.36 and 1.20 at 95%, CI: 0.97-1.49. On the contrary, the risk for AH increased from low to statistically not significant in underground equipment operators (0.85 at 95%, CI: 0.71-1.01) and labourers (0.89 at 95%, CI: 0.69-1.14). PMID- 27266027 TI - [REGIONAL INDICES OF TRACE ELEMENT LEVELS IN HAIR IN CHLILDREN OF THE POPULATION OF THE IRKUTSK REGION]. AB - 747 hair samples of the pre-school aged children from different regions of the Irkutsk Region have been analyzed with the aim to establish the regional reference indices. The measurements were performed by the atomic-absorption method. The population deficiency of the essential microelements of zinc, copper along with the simultaneous excess of magnesium, mercury was revealed to be observed at the territory of the Irkutsk Region. According to the results of the study of mercury level in biological medias of the children population of the Irkutsk region it is possible to mark the unfavorable areas where chronic anthropogenic load has led to the accumulation of mercury in the body. PMID- 27266028 TI - [GENDER VARIABILITY OF MORPHOFUNCTIONAL INDICES IN ADOLESCENTS OF MOUNTAIN ALTAI]. AB - Gender differences in the functioning of the organism of teenagers in extreme climatic conditions of the environment are not been well understood. We estimated the variability of morphofunctional indices in adolescents aged of 11-16 years residing in lowlands and midlands of Mountain Altai in dependence on area of residence, age, and gender The variability of morphological and functional indices of male and female body in a critical period of ontogenesis was found to be dependent in varying degrees on the climatic conditions of the Mountainous Altai. Revealed significant differences in morphofunctional indices depending on the area in boys are more signifcant than in girls. In male adolescents, residing in middleland unlike peers of lowland there was noted functional exertion of the cardiovascular system, as well as delay in physical and sexual development. It testifies about the gender variability of adaptation of an organism depending on factors of environment and higher sensitivity of a male organism during the period of puberty to external negative influences. PMID- 27266029 TI - [SANITATION AND SCHOOL HYGIENE IN THE SCHOOL INSTITUTTIONS OF THE TOBOLSK PROVINCE IN THE LATE XIX CENTURY]. AB - In the article there is considered the history of the development ofsanitary and hygienic standards in school institutions of Tobolsk province in the late XIX century. In comparative terms there is characterized the presented in that period the legal framework regulating of abidance by hygienic and sanitary standards in educational institutions. There was executed an careful analysis of hygienic conditions on the example of the Tobolsk male gymnasium with a comparison of similar conditions in another Siberian educational/childcare institution--the Yenisei female progymnasium. The main sources in the study were reports of educators: I. Gursky--about hygienic living conditions of the inmates of the Tobolsk gymnasium and P.M. Golovachev--about sanitary conditions in the Yenisei female gymnasium. Contemporaries paid a great attention to such health and safety standards as heating, ventilation, lighting, capacity of classrooms and boarding facilities, the violation of which led to a deterioration in the health of students and the growth of the epidemics in mention educational institutions. PMID- 27266030 TI - [THE USE OF RISK INDICES IN PROCEDURES OF VERIFICATION OF BABY FOOD QUALITY CONFORMANCE]. AB - There is considered the possibility of the use of risk indices with regard to their use in certification and validation of conformity assessment and food conformance, including those recommended for children. There were investigated samples of oatmeals, potted meats, liver pate, fruit-vegetable puree. The calculation of risk values was based on original data of quantitative analysis that was performed with the use of thermogravimetric, photometric, titrimetric, and potentiometric methods, as well as methods of gas-liquid chromatography and atomic absorption spectrophotometry. On the base of data of the chemical analysis of the ingredients of a set of food products, including assigned for baby nutrition, all the tested samples were shown to meet the requirements for the controlled regulatory standards on control indices of quality. The calculation of average daily doses of the intake of metal compounds (Cu, Zn, Fe, Na, Ca, Mg) consumed by adult and child's organisms through tested food showed that such doses are allowable since they do not exceed maximum daily dose and average daily requirements. However, some samples were referred to the category of high risk food, because the used method of individual's lifetime risk calculation takes into consideration all possible negative effects (carcinogenic, mutagenic, teratogenic, embryogenic, etc) of the impact of pollutants on the human body. It is shown that in addition to the sanitary and hygienic criteria of food quality, the risks of such food consumption should be taken into consideration by the Technical Regulations and other normative documentations. PMID- 27266031 TI - [INCIDENCE, PREDISPOSING RISK FACTORS FOR THE DEVELOPMENT AND SPREADING OF ACUTE INTESTINAL INFECTIONS IN THE NORTH-EASTERN REGION OF UKRAINE]. AB - Using data of the branch statistical reporting of the State Sanitary and Epidemiological Service in Sumy region and Sumy Regional State Laboratory of Veterinary Medicine, the incidence rate, modern risk factors for the development and spreading of acute infectious diarrheas were determined in the North-Eastern region of Ukraine. Under the current conditions incidence rate indices of acute intestinal infections and food toxicoinfections are within the range of 159.8 193.6 per 100 thousands. pop. Seasonal and epidemical rises are associated with a species of the agent. In the etiological structure of acute diarrheal infections there are dominated viruses, of food toxicoinfections--Klebsiellae pneumoniae, Staphylococcus aureus and Enterobacter cloacae (p < 0.05). Predictors of the complication of epidemiological situation of Shigella infections are the gain in the detection of bacterially contaminated samples of milk and dairy products (r = 0.75), for food toxicoinfections caused by Klebsiellae pneumoniae and Enterobacter cloacae--pastry with cream and cooking meat products (r = 0.64; r = 0.75). Epizootic situation in the region affects on the salmonellosis incidence rate of the population (r = 0.89). There were revealed correlations between the selection of E. coli bacteria from swabs taken from the enterprises of catering, in child care centers and the levels of incidence rates of salmonellosis, acute intestinal infections of unknown etiology (r = 0.59; r = 0.60). Timely detection and sanitation of Shigella carriers are a powerful instrument to reduce the incidence rate of shigellosis (r = 0.83). PMID- 27266033 TI - [CHOICE OF SANITARY-INDICATIVE MICROORGANISMS FOR THE ASSESSMENT OF THE SAFETY OF SPLIT-SYSTEMS]. AB - Purpose of work is a compilation of data about the microflora which colonizes a split-system, with the aim of selection of sanitary-indicative microorganisms, whose presence in the sample would indicate to the need for cleaning and disinfection of split-systems. MATERIALS AND METHODS: In the article there were used data of five years author's scientific inquiry, related to the prevention of respiratory diseases, associated with the usage of a local air conditioning systems. We also use the data from the literature. RESULTS: For selection of "indicative" microorganisms, we proposed the usage of nine criteria, each of them have numeric value from 0 to 3 points (risk for health, prevalence rate of the disease, epidemiological link, speed of split system's colonization, difficulty of cultivation, resistance in the environment, resistance to disinfectants, frequency of detection in home air conditioning systems, frequency of detection in air conditioning systems of public buildings). After the calculation Pseudomonas aeruginosa and Staphylococcus aureus received maximal score (20 points). Therefore, these two types of bacteria are indicative microorganisms. The detection of these microorganisms in split systems will indicate to the contamination of air-conditioning system. This microflora also is a criterion of cleaning and disinfection quality--presence of these microorganisms in the samples after this process will mean that the processing of air conditioning systems was performed poorly. CONCLUSIONS: Split systems are very faster colonized by conditionally pathogenic and pathogenic microflora. To prevent the possible hazard for population's health it is necessary to develop the normative base, according to which sanitary-and-hygienic control over the split-systems working must be carried out. Proposed criteria suggest that Pseudomonas aeruginosa and Staphylococcus aureus are indicative microorganisms, and it's identification in the air-conditioning system would mean risk for health and necessity for cleaning and disinfection. PMID- 27266032 TI - [IMMUNOCYTOCHEMICAL ANALYSIS OF THE DISTURBANCES IN THE STRUCTURE OF SYNAPTONEMAL COMPLEXES IN SPERMATOCYTE NUCLEI IN MICE UNDER EXPOSURE TO ROCKET FUEL COMPONENT]. AB - There was performed an assessment of genotoxic effects of rocket fuel component- unsymmetrical dimethylhydrazine (UDMH, heptyl)--on forming germ cells of male mice. Immunocytochemically there was studied the structure of meiotic nuclei at different times after the intraperitoneal administration of UDMH to male mice. There were revealed following types of disturbances of the structure of synaptonemal complexes (SCs) of meiotic chromosomes: single and multiple fragments of SCs associations of autosomes with a sex bivalent, atypical structure of the SCs with a frequency higher than the reference level. In addition, there were found the premature desinapsis of sex bivalents, the disorder offormation of the genital corpuscle and ring SCs. Established disorders in SCs of spermatocytes, analyzed at 38th day after the 10-days intoxication of animal by the component of rocket fuel, attest to the risk of permanent persistence of chromosomal abnormalities occurring in the pool of stem cells. PMID- 27266034 TI - [COMPUTER TECHNOLOGY FOR ACCOUNTING OF CONFOUNDERS IN THE RISK ASSESSMENT IN COMPARATIVE STUDIES ON THE BASE OF THE METHOD OF STANDARDIZATION]. AB - There was performed an analysis of the accounting of the impact of concomitant variables (confounders), introducing a systematic error in the assessment of the impact of risk factors on the resulting variable. The analysis showed that standardization is an effective method for the reduction of the shift of risk assessment. In the work there is suggested an algorithm implementing the method of standardization based on stratification, providing for the minimization of the difference of distributions of confounders in groups on risk factors. To automate the standardization procedures there was developed a software available on the website of the Institute of Industrial Ecology, UB RAS. With the help of the developed software by numerically modeling there were determined conditions of the applicability of the method of standardization on the basis of stratification for the case of the normal distribution on the response and confounder and linear relationship between them. Comparison ofresults obtained with the help of the standardization with statistical methods (logistic regression and analysis of covariance) in solving the problem of human ecology, has shown that obtaining close results is possible if there will be met exactly conditions for the applicability of statistical methods. Standardization is less sensitive to violations of conditions of applicability. PMID- 27266035 TI - [RANK INDICES METHOD AND ITS USE FOR THE COMPARATIVE ANALYSIS OF POPULATION HEALTH]. AB - There is presented a calculation method aimed to elevate the informative value of the integral indices of the social and hygienic monitoringfor purposes of comparative analysis. The method of rank indices is based on the ranking of monitoring objects on the values of primary indices on the base of which there are calculated the integral such indices as, for example, life expectancy. There are presented results of the use of this method for the comparative analysis of mortality rate in WHO Member States for the period of 1990-2011. There were revealed specialfeatures of mortality trends which cannot be detected when using only mortality rates or the life expectancy. In particular, for Russia there was shown that, in spite of the downward trend in child and adolescent mortality rate observed in the last decade, the country's world rankings for these indices fail to achieve the level of 1990. This means that the competitiveness of the country, sharply declined in the 90's, was not restored until now. There are described some features of the use of the method of rank indices for the analysis of indices of the environment state, public health and its socio-economic determinants. PMID- 27266036 TI - [ELEMENTS OF A SYSTEMATIC APPROACH TO HYGIENIC REGULATION OF XENOBIOTICS]. AB - Hygienic standardization (HS) of chemicals remains to be the one of the effective ways to ensure chemical safety of the population. At that hygienic standards (such as maximum allowable concentrations--MACs) are interrelated and aggregated into the coherent systems. Therefore, the task of the study was in establishment of the logic of inter- standard relations between the existing standards and actualization of legitimate relations of the interrelations such as MACwz/MACatm, (i.e., to systematize standards) and so as CL50/MACwz (reflecting the ratio of reliability). In the suggested systemic approach the benchmark indices of the proposed HS system are the values of the MACwz. Standards for other media, including atmosphere air may be only some compartments of MACwz. The performed studies and calculations allowed to justify and implement the system approach into the practice of HS in Ukraine. There is need for further search for additional solutions in nonreachability of LC50 in the experiment, justification of standards for the population in the absence of MACwz, comparison with the data of normative databases of other countries. It is necessary to introduce the value of permissible deviation from the requirements of the systemness, to embody conditions (1)-(7) into the general principle of the prohibition of greater deviation and to harmonize acting and newly introduced standards within frameworks of modern ideology and methods of HS of harmful substances. This opens up broad prospects for the new phase of HS and a significant increase in the reliability of results obtained by the various methods and in different laboratories. PMID- 27266037 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Editorial: Fatty liver important?]. PMID- 27266038 TI - [linical Importance of Non-alcoholic Fatty Liver Diseases. Topics II Clinical impact of epidemiological studies]. PMID- 27266039 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Topics: II. Complexity in pathogenesis of nonalcoholic fatty liver disease]. PMID- 27266040 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Topics: III. Relation with Type II diabetes: regulation by hepatokines]. PMID- 27266041 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Topics: IV. Relation of NAFLD with lifestyle-related disease including obesity, dyslipidemia and hypertension]. PMID- 27266042 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Topics: V. Extrahepatic manifestations: cerebral and cardiovascular diseases, chronic kidney disease]. PMID- 27266043 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Topics: VI. Diagnostic procedures: when referring to specialists]. PMID- 27266045 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Topics: VIII. The prognosis and follow-up]. PMID- 27266044 TI - [Clinical Importance of Non-alcoholic Fatty Liver Diseases. Topics: VII. Routine treatment: when referring to specialists]. PMID- 27266046 TI - [Case Report; Gastric mucosa in patients with autoimmune thyroiditis. (Discussion about a case of autoimmune polyendocrine syndrome 3B)]. PMID- 27266047 TI - [Case Report; A case of vasculitis with multiple hepatic artery aneurysms]. PMID- 27266048 TI - [Case Report; A case of systemic capillary leak syndrome]. PMID- 27266049 TI - [Case Report; A case of Lemierre's syndrome associated with necrotizing fasciitis and septic embolization]. PMID- 27266050 TI - [The Cutting-edge of Medicine; Clinico-pathogenetic background and approach for early detection of lung cancer]. PMID- 27266051 TI - [The Catting-edge of Medicine; Anti-viral therapies for chronic hepatitis C]. PMID- 27266052 TI - [Report from the 21th Tokai Chapter Educational Seminar: Practice of community medicine by Japanese internists in a new era: commitment to society's implementation of the integrated community care system]. PMID- 27266053 TI - In Memoriam: John F. Kurtzke, MD, FACP, FAAN 1926-2015. PMID- 27266054 TI - [Prevention - is it useful?]. PMID- 27266055 TI - [Concept and classification of diabetic complications]. PMID- 27266056 TI - [Microangiopathy in Japanese patients with diabetes]. PMID- 27266057 TI - [Features of Japanese diabetic macroangiopathy]. PMID- 27266058 TI - [Genetic factors for susceptibility to diabetic microvascular complications]. PMID- 27266059 TI - [Large-scale clinical studies on diabetic complications]. PMID- 27266060 TI - [Management for diabetes mellitus to prevent its complications]. PMID- 27266061 TI - [AGE-RAGE system]. PMID- 27266062 TI - [Polyol pathway]. PMID- 27266063 TI - [Protein kinase C pathway]. PMID- 27266064 TI - [Mitochondrial reactive oxygen species]. PMID- 27266065 TI - [Oxidative stress and chronic inflammation]. PMID- 27266066 TI - [Rho/Rho-kinase]. PMID- 27266067 TI - [Diabetic ketoacidosis]. PMID- 27266068 TI - [Hyperglycemic hyperosmolar state]. PMID- 27266069 TI - [Diabetes mellitus and infectious disease]. PMID- 27266070 TI - [Clinical epidemiology of diabetic retinopathy]. PMID- 27266071 TI - [Etiology of diabetic retinopathy]. PMID- 27266072 TI - [Pathophysiology and classification of diabetic retinopathy]. PMID- 27266073 TI - [Diagnosis for diabetic retinopathy]. PMID- 27266074 TI - [Medical therapy for diabetic retinopathy]. PMID- 27266075 TI - [Vitrectomy for proliferative diabetic retinopathy]. PMID- 27266076 TI - [Diabetic retinopathy treatment and management--current and future regenerative medicine]. PMID- 27266077 TI - [Diabetic macular edema--pathogenesis, diagnosis and treatment]. PMID- 27266078 TI - [Diagonosis and treatment of cataract and glaucoma caused by diabetes mellitus]. PMID- 27266080 TI - [Emerging new aspects on diabetic nephropathy]. PMID- 27266079 TI - [Epidemiology of diabetic nephropathy]. PMID- 27266081 TI - [Relationship between the Classification of Diabetic Nephropathy 2014 and the classification of CKD stages]. PMID- 27266082 TI - [Standards for early diagnosis of diabetic nephropathy]. PMID- 27266083 TI - [eGFR, urinary excretion of albumin, urinary excretion of protein, blood urea nitrogen, cystatin C]. PMID- 27266084 TI - [Urinary podocyte and urinary podocalyxin; markers for diabetic nephropathy]. PMID- 27266085 TI - [Urinary type IV collagen and urinary L-FABP]. PMID- 27266086 TI - [Efficacy and effectiveness of protein restriction for the treatment of diabetic nephropathy]. PMID- 27266087 TI - [Physical exercise in diabetic nephropathy]. PMID- 27266088 TI - [Treatment of diabetic nephropathy, particularly focusing on drug therapy]. PMID- 27266089 TI - [Current status and perspective of regenerative medicine for diabetic nephropathy]. PMID- 27266091 TI - [Epidemiology of diabetic neuropathy]. PMID- 27266090 TI - [The management of diabetic patients on hemodialysis or peritoneal dialysis]. PMID- 27266092 TI - [Pathogenesis of diabetic neuropathy]. PMID- 27266093 TI - [Pathophysiology of diabetic polyneuropathy]. PMID- 27266094 TI - [Clinical staging of diabetic polyneuropathy]. PMID- 27266095 TI - [Analysis of small-fiber neuropathy using novel various autonomic function tests]. PMID- 27266096 TI - [Achilles tendon reflex, vibration sensation threshold, and nerve conduction study for the evaluation of the large fiber neuropathy in diabetes mellitus]. PMID- 27266097 TI - [Intra-epidermal nerve fiber density and intra-epidermal electrical stimulation for diagnosis of diabetic neuropathy]. PMID- 27266098 TI - [Medical treatment of diabetic neuropathy]. PMID- 27266099 TI - [Cell-based therapy]. PMID- 27266100 TI - [Possibility of regenerative medicine on diabetic neuropathy]. PMID- 27266101 TI - [Epidemiology of the stroke due to diabetes mellitus]. PMID- 27266102 TI - [Pathophysiology of stroke, due to diabetes mellitus]. PMID- 27266103 TI - [Diagnosis and examination of stroke associated with diabetes mellitus]. PMID- 27266104 TI - [Stroke therapy in diabetes mellitus patients]. PMID- 27266105 TI - [Preventive surgery for diabetes-related stroke]. PMID- 27266106 TI - [Epidemiology of coronary heart diseases in the patients with diabetes]. PMID- 27266108 TI - [Diagnostic approach and modalities for coronary artery disease in patients with diabetes mellitus]. PMID- 27266107 TI - [Etiology and pathology of coronary artery disease in diabetes patients]. PMID- 27266109 TI - [Optimal medical therapy in diabetic patients with coronary artery disease]. PMID- 27266110 TI - [Coronary artery bypass surgery for diabetic patients]. PMID- 27266111 TI - [Epidemiology, etiology, pathology, and pathophysiology of arteriosclerosis obliterans]. PMID- 27266112 TI - [Diagnosis of peripheral arterial disease]. PMID- 27266113 TI - [Medical treatment for atherosclerosis obliterans]. PMID- 27266114 TI - [Open surgical treatment for peripheral arterial occlusive diseases]. PMID- 27266115 TI - [Therapeutic angiogenesis for refractory peripheral arterial disease (PAD)]. PMID- 27266116 TI - [Clinical epidemiology of diabetic foot]. PMID- 27266117 TI - [Diabetic foot classification for Asian--Kobe classification]. PMID- 27266118 TI - [Treatment of diabetic foot]. PMID- 27266119 TI - [Prevention and care of diabetic foot ulcer]. PMID- 27266120 TI - [Diabetes mellitus with hypertension]. PMID- 27266121 TI - [Treatment of diabetes mellitus with obesity and metabolic syndrome]. PMID- 27266122 TI - [Diabetes mellitus with dyslipidemia]. PMID- 27266123 TI - [Diabetes mellitus with sarcopenia or frailty]. PMID- 27266124 TI - [Diabetes and cancer risk: evidence from epidemiological studies]. PMID- 27266125 TI - [Molecular mechanism underlying cancer development in diabetes]. PMID- 27266126 TI - [Diabetes mellitus, Helicobacter pylori, and gastric cancer]. PMID- 27266128 TI - [Various cancers related type 2 diabetes mellitus: Pancreatic cancer]. PMID- 27266127 TI - [Association between diabetes mellitus and risk of liver cancer]. PMID- 27266129 TI - [Colorectal cancer]. PMID- 27266130 TI - [Correlation between diabetes mellitus and cancers of various organ--breast cancer]. PMID- 27266131 TI - [Diabetes mellitus and endometrial cancer]. PMID- 27266132 TI - [Pioglitazone and the risk of bladder cancer]. PMID- 27266133 TI - [The impact of anti-diabetic therapy on cancer development]. PMID- 27266134 TI - [Diabetes mellitus and COPD]. PMID- 27266135 TI - [Liver disease (NAFLD, NASH)]. PMID- 27266136 TI - [Osteoporosis]. PMID- 27266137 TI - [Major depression and insomnia comorbid with diabetes]. PMID- 27266138 TI - [The relationship between diabetes and periodontal disease]. PMID- 27266140 TI - [Epidemiology of type 1 diabetes in children and adolescents]. PMID- 27266139 TI - [Neonatal diabetes mellitus]. PMID- 27266141 TI - [Current status and future tasks on childhood-onset diabetes]. PMID- 27266142 TI - [Diagnosis and treatment of type 1 diabetes mellitus in children]. PMID- 27266143 TI - [Diagnosis and treatment in children with type 2 diabetes mellitus]. PMID- 27266144 TI - [Diabetes education for patients and their surroundings in pediatrics]. PMID- 27266145 TI - [Pathogenesis, diagnosis, and treatment of type 2 diabetes in adolescence]. PMID- 27266146 TI - [Management of hyperglycemic disorders in pregnancy]. PMID- 27266147 TI - [Energy and glucose metabolism in the elderly]. PMID- 27266148 TI - [Clinical significance of comprehensive geriatric assessment in diabetic elderly]. PMID- 27266149 TI - [Clinical features of diabetes mellitus in the elderly]. PMID- 27266150 TI - [Examination and diagnosis in older diabetic mellitus]. PMID- 27266151 TI - [Key notes of glycemic control in elderly patients with diabetes]. PMID- 27266152 TI - [Medication for the elderly diabetes]. PMID- 27266153 TI - [Diet of elderly diabetic patients]. PMID- 27266154 TI - [Elderly diabetic patients and exercise]. PMID- 27266155 TI - [Comprehensive management of dementia in old people with diabetes]. PMID- 27266156 TI - [Diabetes due to endocrine disorders]. PMID- 27266157 TI - [Pancreatic diabetes: pathophysiology and treatment]. PMID- 27266158 TI - [Pathogenesis of hepatogenous diabetes]. PMID- 27266159 TI - [Drug-induced diabetes mellitus]. PMID- 27266160 TI - [Monogenic form of diabetes mellitus]. PMID- 27266161 TI - [Insulin autoimmune syndrome]. PMID- 27266162 TI - [Current status and issues of diabetes class]. PMID- 27266163 TI - [DialBetics: Smartphone-Based Self-Management for Type 2 Diabetes Patients]. PMID- 27266164 TI - [The current state of summer camps for diabetic children in Japan]. PMID- 27266165 TI - [Current status and challenge of certified diabetes educator(CDE)]. PMID- 27266166 TI - [Behavior modification in diabetic patients]. PMID- 27266167 TI - [Sick day rule]. PMID- 27266168 TI - [Prevention of hypoglycemia]. PMID- 27266169 TI - [A strategy for increasing adherence in patients with type 2 diabetes]. PMID- 27266170 TI - [Current situations and issues of clinical network for diabetes in regions]. PMID- 27266171 TI - [Cooperation and role allotment between diabetes specialists and internists for medical care of patients with diabetes]. PMID- 27266172 TI - [Importance of team-based management of diabetes mellitus]. PMID- 27266173 TI - [Current status and issues of clinical-pass in diabetes]. PMID- 27266174 TI - [The manual for diabetes treatment in times of disaster]. PMID- 27266175 TI - [Role of sportology for the prevention and treatment of diabetes mellitus]. PMID- 27266176 TI - [Anti-oncogenic effect of metformin]. PMID- 27266177 TI - [Mechanism of salt-sensitive hypertension in diabetes mellitus]. PMID- 27266178 TI - [Perioperative glycemic management in cardiac surgery]. PMID- 27266179 TI - [Cost-effectiveness analysis for diabetes care]. PMID- 27266180 TI - [ENHANCEMENT OF AGROBACTERIAL TRANSFORMATION OF PLANTS USING PROTEIN KINASE INHIBITORS TRIFLUOPERAZINE AND GENISTEIN]. AB - The effect of different concentrations of protein tyrosine kinase inhibitor, genistein and serine/threonine protein kinase inhibitor, trifluoperazine, on the frequency of Agrobacterium-mediated transformation of leaf explants of N. tabacum was investigated. The influence of different concentrations of trifluoperazine in the range from 10 to 300 MUM was investigated. It was found that 10 MUM trifluoperazine provoked the increase of the frequency of agrobacterial transformation of tobacco leaf disks on 25%. In parallel, the influence of different concentrations of genistein in the range from 10 to 100 MUM was investigated. It was found 100 MUM genistein provoked the increase of the frequency of agrobacterial transformation of tobacco leaf disks on 12%. PMID- 27266181 TI - GENETIC DIVERSITY OF SOME IRANIAN SWEET CHERRY (PRUNUS AVIUM) CULTIVARS USING MICROSATELLITE MARKERS AND MORPHOLOGICAL TRAITS. AB - The aim of this study was to characterize 23 important Iranian sweet cherry (Prunus avium) cultivars collected from different provinces of Iran and 1 foreign cultivar, which was used as control, considered for breeding programs by using 21 microsatellite markers and 27 morphological traits. In sweet cherry (Prunus avium) accessions, leaf, fruit, and stone morphological characters were evaluated during two consecutive years. The study revealed a high variability in the set of evaluated sweet cherry accessions. The majority of important correlations were determined among variables representing fruit and leaf size and variables related to color. Cluster analysis distinguished sweet cherry accessions into two distinct groups. Principal component analysis (PCA) of qualitative and quantitative morphological parameters explained over 86.59% of total variability in the first seven axes. In PCA, leaf traits such as leaf length and width, and fruit traits such as length, width, and weight, and fruit flesh and juice color were predominant in the first two components, indicating that they were useful for the assessment of sweet cherry germplasm characterization. Out of 21 SSR markers, 16 were polymorphic, producing 177 alleles that varied from 4 to 16 alleles (9.35 on average) with a mean heterozygosity value of 0.82 that produced successful amplifications and revealed DNA polymorphisms. Allele size varied from 95 to 290 bp. Cluster analyses showed that the studied sweet cherry genotypes were classified intofive main groups based mainly on their species characteristics and SSR data. In general, our results did not show a clear structuring of genetic variability within the Iranian diffusion area of sweet cherry, so it was not possible to draw any indications on regions of provenance delimitation. The results of this study contribute to a better understanding of sweet cherry genetic variations in Iran, thus making for more efficient programs aimed at preserving biodiversity and more rational planning of the management of reproductive material. PMID- 27266182 TI - [PLEIOTROPIC EFFECTS OF GIBBERELLIN-SENSITIVE AND GIBBERELLIN-INSENSITIVE DWARFING GENES IN COMMON WHEAT OF THE SOUTHERN STEP REGION OF BLACK SEA]. AB - Investigations of the pleiotropic effects of GA-sensitive (Rht8) and GA insensitive (Rht-B1, Rht-D1) dwarfing genes and a gene that determines the response of plants to photoperiod--Ppd-D1 were carried out for three years in the southern step region of Black Sea bank on five different genetic backgrounds. It is shown that in addition to direct effects on plant height GA-sensitive and GA insensitive dwarfing genes have pleiotropic effects on all studied traits except the number of fertile spikelets. Presence of the dwarfing genes in the genotype of tall forms led to the decrease of stem and ear length, and at the same time to the increase of ear density. The number of spikelets per spike decreased due to sterile spikelets, whereas the number of fertile spikelets did not change. There was a significant increase in the number of grains per ear as a result of increasing of spikelets in ears. The number and weight of grains did not decrease, even though the plants were characterized by a smaller number of productive stems. The presence of Rht8x allele on genetic background of variety Stepnyak resulted in a significant decrease of plants productivity. However, in combination with Ppd-D1a allele plants with Rht8x increased the potential productivity, and surpassed the parental form (Rht8a Ppd-D1b). The presence of Rht-B1e allele resulted in reduction of grain mass per spike and 1000-grain weight, increase of l/h, and left the number of grains per spike stable in comparison with Rht8c. PMID- 27266183 TI - EFFECT OF WATERLOGGING STRESS ON MEIOTIC COURSE, TETRAD FORMATION AND POLLEN FERTILITY OF SESBANIA PEA. AB - Sesbania cannabina a multipurpose leguminous crop of family Fabaceae, is widely adaptable to adverse climatic conditions such as waterlogging, drought and high salinity. Flooding and water logging are very common phenomena and there may be possibility to become more serious alarms for environment, which is progressively deteriorated by human beings by their anthropogenic activities, polluting the atmosphere. Flooding provides a case of natural selection to the nature which selects the plants which are more adaptable to this condition and renders themselves to survive due to this tolerance or resistance behavior. Present study envisages the effect of waterlogging stress on chromosomal biology of Sesbania pea. To study the effect of waterlogging stress on microsporogensis of Sesbania cannabina, presoaked seeds were sown in experimental pots. Permanent waterlogged condition is created by shifting pots in water filled tanks. Cytological studies showed various types of chromosomal aberrations induced by waterlogging stress and reduction in pollen fertility was also encountered. PMID- 27266184 TI - IMMUNOHISTOCHEMICAL AND BIOCHEMICAL ANALYSIS OF MAMMARY GLAND TUMOURS OF DIFFERENT AGE PATIENTS. AB - Immunohistochemical and biochemical study of infiltrative ductal breast carcinoma and tissue adjacent to the tumour revealed a particular molecular profile and characteristics of the oxidant-antioxidant status neoplasms depending on the age of the patients and the presence of metastases in regional lymph nodes. Some causes of high aggressiveness and low hormone sensitivity of tumours in premenopausal women, as well as stability and high metastatic potential of tumours in postmenopausal women have been found. PMID- 27266185 TI - PIXEL SENSIBLE LOCAL BAND ANALYSIS IN MICROSCOPIC CHROMOSOME IMAGES USING CSPA. AB - In chromosome analysis, local band analysis plays the main role to identify the perfect matched chromosome in metaspread images to attain the karyotyping. Literature investigations are narrow in chromosome image band analysis due to the higher complexities. In this paper, Pixel level based Conditional Seed Point Algorithm (CSPA) is proposed. This simulation algorithm separates the weak band region to the strong band region, and the strong band region area evaluated was based on the Region of Seed condition Points. This algorithm works well for different intensity levels and adopts the structural changes to identify the bands in image. This algorithm was simulated in more than 450 individual chromosomes to identify the local bands in the chromosome images and provided the accuracy more than 96%. PMID- 27266186 TI - [INVOLVEMENT OF PLANT CYTOSKELETON INTO CELLULAR MECHANISMS OF METALS TOXICITY]. AB - This review summarizes published date and the results of the author's own researches cantering the participation of plant cells cytoskeleton. It is considered cytotoxic impact of metals on the cytoskeleton's components, including microtubules and actin filaments. Particular attention is paid to the cellular and molecular mechanisms of influence of metals on cytoskeleton. We discussed the most probable binding sites of heavy metals and alternative mechanisms of their impact on the cytoskeleton. PMID- 27266187 TI - B CHROMOSOMES IN ANGIOSPERM--A REVIEW. AB - A review article on B chromosomes (Bs) in angiosperms is documented considering occurrence, morphology, polymorphic B forms, divisional phase heterogeneity, chromatin organization and gene content, sequence composition, origin, evolutionary aspects and significant role on host with an objective to foresee the evolutionary perspectives as it still remains an enigma. Irrespective of the origin of Bs, it seems that they have attained the following modifications, namely, insertion of centromeric and telomeric sequences, structural reorganization and procuring mitotic and meiotic drives but shows genetic inertness and present in the host as selfish DNA. In the context, few questions are raised. Further, scientific quest may unravel the unexplored information about Bs to ascertain its evolutionary perspectives, if any. PMID- 27266188 TI - [WAR AND WORLD OF ERWIN CHARGAFF (DEDICATED TO 110 ANNIVERSARY OF BIRTH)]. AB - The article shortly describes the life path of Erwin Chargaff, one of the most famous figures in the history of molecular biology and genetics. Chargaff was born in Chernivtsi (Austria-Hungary, now Ukraine) but during the First World War his family was forced to move to Vienna. After graduating from the University of Vienna, Chargaff worked in Berlin, where he studied bacterial lipids. Due to Nazis coming to power in Germany, Chargaff moved to Paris and later (1935) emigrated to the USA and obtained a position at Columbia University, where he initially investigated the role of phospholipids in blood clotting. In 1944, applying novel methods Chargaff initiated intensive investigation of the chemical composition of nucleic acids from taxonomically distant species and established two rules which were later named after him. The first Chargaff's rule provided a significant support to Watson and Crick in construction of their double helical DNA model. The explosion of atomic bombs over Hiroshima and Nagasaki forced Chargaff to think about the moral responsibility of researchers and science to mankind. He begins to raise these issues in the press and manifests himself as a talented journalist, who criticized the bureaucratization of science and its transformation into a way of earning money. Despite decades of life in America, spiritually Erwin Chargaff always remained a European, who never forgot his roots and always remembered his native land. PMID- 27266189 TI - [Radiographic diagnosis of vertical root fracture]. AB - Vertical root fracture (VRF) is different from odontoclasis caused by trauma or injury. VRF is defined as a complete or incomplete fracture of roots caused by long-term and persistent stimulus, such as excessive forces from mastication or occlusion, improper tooth anatomy, and tooth treatment accident. Early diagnosis of VRF is essential to prevent the absorption of alveolar bone, thereby improving prognosis. Radiographic examination is the most common and effective evaluation method for VRF. Cone beam computed tomography can provide three-dimensional information for fracture details, which are more precise than traditional periapical films. In this paper, we present the radiographic features, differential diagnosis, and new treatment techniques for VRF. PMID- 27266190 TI - [Fabrication and evaluation of hydroxyapatite-chitosan scaffold via simulated body fluid biomimetic mineralization]. AB - OBJECTIVE: This research aimed to fabricate a hydroxyapatite (HA)-chitosan scaffold via simulated body fluid (SBF) biomimetic mineralization and determine how mineralization time affects scaffold construction and cell compatibility. METHODS: The HA-chitosan scaffolds were fabricated by freeze-drying technique and then subjected to precalcification, also known as alternative soaking method. Afterward, precalcificated scaffolds were placed into the SBF to conduct the mineralization process. Mineralization time was set at 7, 14, and 21 days, corresponding to three experimental groups. Pure chitosan scaffolds acted as the control group, and the physical and chemical properties of the four groups were tested. Osteogenic-induced adipose-derived stem cells (ADSCs) were seeded into the scaffolds to investigate the scaffolds' cell compatibility. RESULTS: The mineral substance of the 14-day group exhibited a uniform distribution. The crystal composition of the mineral substance suited the HA's features. The compressive elastic modulus increased along with the extension of mineralization time. The 21-day group showed a statistically significant increase in compressive elastic modulus compared with the control group (P < 0.05). The cell proliferation level of the 14-day group was significantly the highest among the three experimental groups (P < 0.05). The calcium ion and the type I collagen had the highest secretion amount when the cells were seeded into the 14-day group. CONCLUSION: The SBF biomimetic mineralization method can be used to fabricate HA chitosan bone-tissue-engineering scaffolds. The biological compatibility, as well as the chemical and physical properties, reached the optimum levels at day 14. PMID- 27266191 TI - [Calcitonin gene-related peptide inhibits the expression of Nod-like receptor protein 3 to Dromote osteoblast differentiation in mouse osteoblasts in vitro]. AB - OBJECTIVE: This study aims to investigate the regulatory effects of calcitonin gene-related peptide (CGRP) on Nod-like receptor protein 3 (NLRP3) and interleukin-1beta (IL-1beta) to promote osteoblast differentiation. METHODS: Different concentrations of CGRP (0, 10, 30, 100 ng . mL-1) were added to mouse osteoblasts in vitro. The mRNA and protein expression levels of both NLRP3 and IL 1beta were examined using Real-time polymerase chain reaction and Western blot, respectively. Moreover, the concentrations of IL-1beta protein and intracellular reactive oxygen species (ROS) were detected using enzyme-linked immunosorbent assay and flow cytometry, respectively. The osteogenic differentiation of mouse osteoblasts was identified through alizarin red staining. RESULTS: The protein and mRNA expression levels of both NLRP3 and IL-1beta significantly decreased (P < 0.05) with increasing CGRP concentration. Moreover, the contents of intracellular ROS gradually decreased (P<0.05). The osteogenic differentiation of the osteoblasts was more enhanced in the group treated with 100 ng . mL-1 CGRP than in the empty group (0 ng . mL-1 CGRP). CONCLUSION: CGRP promotes osteoblast differentiation by inhibiting the expression of inflammatory factors. PMID- 27266192 TI - [Expression of heat shock protein 27 in cigarette smoke extract-induced injury of human gingival fibroblasts]. AB - OBJECTIVE: This research aimed to observe the expression of heat shock protein 27 (HSP27) in human gingival fibroblasts (HGFs) cell injury induced by different concentrations of cigarette smoke extract (CSE). METHODS: The third to eighth generations of cultured HGFs were treated with serially diluted CSE of different concentrations (0, 2.5%, 5.0%, 12.5%, 25.0%, 50.0%). Wound-healing assay was performed to determine the migration of HGFs, and Western blot was used to determine the expression of HSP27. RESULTS: The migration capability of HGFs weakened with the increase of CSE concentration. HSP27 expression was negative in normal HGFs but positive in CSE-intervened HGFs in a concentration-dependent manner. CONCLUSION: HSP27 concentration increased in the CSE-induced injury of HGFs. This finding suggests that HSP27 plays an important role in CSE-induced epithelial injury. PMID- 27266193 TI - [Effects of different pH conditions on ffh gene expression in Streptococcus mutans]. AB - OBJECTIVE: This research aimed to detect the expression levels of ffh gene in Streptococcus mutans (S. mutans) UA159 under different pH conditions, analyze the effect of pH on the expression of ffh gene in S. mutans, and identify the factors regulating the ffh gene expression. METHODS: Samples of S. mutans were collected at different growth stages (4 h, 18 h) and pH values (pH 4.0-7.0). Fluorescence quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the relative mRNA expression and trend of the target gene ffh in S. mutans at different growth stages and pH values. RESULTS: qRT-PCR results showed that the ffh gene expression decreased along with pH at 4 h, but the expression increased with decreasing pH at 18 h. Under the same pH conditions, the ffh gene expression was significantly different between 4 h and 18 h (P < 0.05). CONCLUSION: Growth stage and pH value influenced the ffh gene expression in S. mutans. PMID- 27266194 TI - [Relationship between transforming growth factor-beta1 and interleukin-10 single nucleotide polymorphism and susceptibility of recurrent aphthous ulcer]. AB - OBJECTIVE: To explore the possible relationship between recurrent aphthous ulcer (RAU) and single nucleotide polymorphism (SNP) of transforming growth factor beta1 (TGF-beta1)-509T/C and interleukin-10 (IL-10)-1082A/G sites. METHODS: A total of 138 RAU patients were recruited for this study. The control group consisted of 124 subjects. TGF-beta1-509T/C and IL-10-1082A/G sites were detected by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) and sequence specific primer-polymerase chain reaction (SSP-PCR). Relative risk ratios were estimated by odds ratios (OR) and 95% confidence interval (95%CI). RESULTS: Significant differences were found in the genotype frequencies or allele frequencies of TGF-beta1-509T/C and IL-10-1082A/G sites between the RAU patients and controls (P < 0.05). CT genotype (OR = 1.231, 95% CI = 0.702-2.160), TT genotype (OR = 2.482, 95% CI = 1.250-4.927), and T allele (OR = 1.465, 95% CI = 1.036-2.074) at the TGF-beta1-509 site exhibited high risks. AG genotype (OR = 1.391, 95% CI = 0.808-2.396), GG genotype (OR = 4.165, 95% CI = 1.944-8.924), and G allele (OR = 2.134, 95% CI = 1.474-3.089) at the IL-10-1082A/G site also showed high risks. CONCLUSION: TGF-beta1-509T/C and IL-10-1082A/G sites are associated with the risk of RAU. The TGF-beta1 gene-509T allele and IL-10 gene-1082G allele may serve as genetic determinants for RAU. PMID- 27266195 TI - [Effect of MT01/PEN complexes on the expression of osteoprotegerin and receptor activator of nuclear factor kappaB ligand in human osteoblast-like cell line MG63]. AB - OBJECTIVE: This study aims to synthesize MTO1 (a kind of oligodeoxynucleotides) and N-isopropylacrylamide-modified polyethylenimines (PEN) complexes (MT01/PEN) as well as to investigate the effect of the complexes on the expression of osteoprotegerin (OPG) and the receptor activator of nuclear factor kappaB ligand (RANKL) in the human osteoblast-like cell line MG63. METHODS: MG63 cells were transfected by MT01/PEN complexes formed with three different mass ratios (1:2, 1:4, 1:6) of MT01 to PEN. MT01 and MT01-s were used as positive control. Enzyme linked immunosorbent assay and real-time polymerase chain reaction were performed to estimate the amount of OPG and RANKL released into the culture media and in MG63 at 24, 48, 72 h. RESULTS: MG63 responded to the MT01/PEN complexes by significantly upregulating the OPG on the protein and mRNA levels (P < 0.05). The protein and mRNA levels of RANKL were lower in most of the groups with complexes, and the OPG/RANKL ratio were higher (P < 0.05). MG63 were affected by the MT01/PEN complexes with different mass ratios, particularly when the ratio was 1:6. CONCLUSION: MT01 can enhance the promotion of ossification by establishing the delivery system with PEN. PMID- 27266196 TI - [Effect of Kou Yan Qing Ke Li on the prevention and treatment of radiation induced oral mucositis in patients with nasopharyngeal carcinoma]. AB - OBJECTIVE: The effect of Kou Yan Qing Ke Li on the prevention and treatment of radiation-induced oral mucositis was investigated in patients with nasopharyngeal carcinoma. METHODS: Sixty patients with nasopharyngeal carcinoma to be treated with radiotherapy were randomized into two groups: the experimental and control groups. The experimental group (30 patients) was treated with Kou Yan Qing Ke Li during the full course of radiotherapy. The control group (30 patients) rinsed their mouths in the same way with mouth washes containing 0.9% sodium chloride injection, lidocaine, dexamethasone, vitamin B2 and B2 gargle liquid mixture, when grade 2 and above radiation-induced oral mucositis appeared in the process of radiation. Radiation-induced oral mucositis was assessed according to the radiation therapy oncology group criteria. The time of occurrence and degree of pain grade were compared between the two groups. RESULTS: The first onset of oral mucositis in the experimental group (12.40 d +/- 2.74 d) was later than that in the control group (9.46 d +/- 1.39 d) (t = 5.241, P < 0.001), whereas the grade of pain and acute radiation mucositis was lower in the experimental group than that in the control group. The difference was statistically significant. CONCLUSION: Kou Yan Qing Ke Li could delay the time of occurrence of radiation induced oral mucositis, reduce the severity of radiation stomatitis, alleviate the pain of patients, improve the clinical symptoms of patients, and effectively prevent and treat radiation-induced oral mucositis in patients with nasopharyngeal carcinoma. PMID- 27266197 TI - [Correlation analysis of Filifactor alocis detection with periodontal status]. AB - OBJECTIVE: The study investigated the epidemiology of Filifactor alocis (F. alocis) in subgingival plaque samples from subjects with different periodontal statuses. The relationship between the prevalence of F. alocis and clinical periodontal parameters was also analyzed. METHODS: Subgingival plaque samples and periodontal data were collected from 68 healthy sites (H groups) in 17 healthy subjects, 64 healthy (G-H group) and 76 diseased sites (G-D group) in 19 patients with chronic gingivitis, and 36 healthy (P-H group) and 56 diseased sites (P-D group) in 14 patients with chronic periodontitis. The plaque samples were analyzed by polymerase chain reaction, and possible correlations between the F. alocis detection rate and the bleeding index, probing depth, or clinical attachment level were determined. RESULTS: The detection levels of F. alocis increased in both healthy and diseased groups. The lowest level at 30.88% (21/68) was noted in the H group, whereas the highest level at 91.07% (51/56) was obtained from the P-D group. A significant correlation was found between the F. alocis detection levels and periodontal disease condition (P < 0.000 1). Further analyses showed that a significant correlation also existed between the detection level of F. alocis and the abnormal clinical periodontal parameters, namely, bleeding index, probing depth, and clinical attachment loss. The odds ratios were 5.26, 8.85, and 11.65, respectively. CONCLUSION: F. alocis was found at increased levels in subjects with periodontal disease. The presence of F. alocis increases the risk of sites with abnormal clinical periodontal parameters. PMID- 27266198 TI - [Effect of fluoride concentration on the corrosion behavior of cobalt-chromium alloy fabricated by two different technology processes]. AB - OBJECTIVE: This study aims to determine the effect of fluoride concentration on the corrosion behavior of cobalt-chromium alloy fabricated by two different technology processes in a simulated oral environment. METHODS: A total of 15 specimens were employed with selective laser melting (SLM) and another 15 for traditional casting (Cast) in cobalt-chromium alloy powders and blocks with the same material composition. The corrosion behavior of the specimens was studied by potentiodynamic polarization test under different oral environments with varying solubilities of fluorine (0, 0.05%, and 0.20% for each) in acid artificial saliva (pH = 5.0). The specimens were soaked in fluorine for 24 h, and the surface microstructure was observed under a field emission scanning electron microscope after immersing the specimens in the test solution at constant temperature. RESULTS: The corrosion potential (Ecorr) value of the cobalt-chromium alloy cast decreased with increasing fluoride concentration in acidic artificial saliva. The Ecorr, Icorr, and Rp values of the cobalt-chromium alloy fabricated by two different technology processes changed significantly when the fluoride concentration was 0.20% (P < 0.05). The Ecorr, Icorr, and Rp values of the cobalt chromium alloy fabricated by two different technology processes exhibited a statistically significant difference. The Icorr value of the cobalt-chromium alloy cast was higher than that in the SLM group cobalt-chromium alloy when the fluoride concentration was 0.20% (P < 0.05). The Ecorr, tRp alues of the cobalt chromium alloy cast were lower htan those of the SLM group cobalt-chromium alloy when the fluoride concentration was 0.20% (P< 0 .05). CONCLUSION: Fluoride ions adversely affected the corrosion resistance of the cobalt-chromium alloy fabricated by two different technology processes. The corrosion resistance of the cobalt-chromium alloy cast was worse than that of the SLM group cobalt-chromium alloy when the fluoride concentration was 0.20%. PMID- 27266199 TI - [Effects of thermal and mechanical cycling on the metal-ceramic bond strength of machine-milled Ti2448 alloy and pure titanium]. AB - OBJECTIVE: To evaluate the effects of thermal and mechanical cycling on the metal ceramic bond strength of machine-milled Ti2448 alloy and commercial pure titanium (cp Ti). METHODS: Ceramic-cp Ti (n = 30) specimens and ceramic-Ti2448 combinations (n = 30) were prepared in accordance with ISO 9693. The specimens from each metal-ceramic combination were randomly divided into three subgroups. In group A or the control group, the specimens were only stored in distilled water for 24 h at 37 degrees C; in groups B and C, the specimens were subjected to 3,000 cycles of thermal cycling between 5 and 55 degrees C for a dwell time of 60 s and to mechanical cycling of 20,000 or 40,000 cycles with 50 N load and 4 Hz in distilled water at 37 degrees C. A crack initiation test was performed using a universal testing machine in accordance with ISO 9693. Failure types at the metal-ceramic interface and the morphological and elemental composition of this interface were analyzed using a scanning electron microscope and an energy dispersive spectrometer. Statistical analysis was performed via two-way ANOVA and Tukey's adjustment test (alpha = 0.05). RESULTS: The bond strength of the ceramic Ti2448 combination was significantly higher than that of the ceramic-cp Ti combination regardless of fatigue conditions (44.86 MPa +/- 1.75 MPa and 29.21 MPa +/- 2.20 MPa for Ti2448 and cp Ti, respectively; P < 0.01). The mean bond strengths of ceramic-cp Ti and ceramic-Ti2448 combinations in group C were significantly lower than that of group A (P < 0.01). Although ceramic-cp Ti combination failed adhesively at the metal-ceramic interface without the ceramic on the substrate surface, Ti2448 frameworks exhibited cohesive failure; as a result, large amounts of residual porcelain were retained on the specimens. CONCLUSION: The metal-ceramic bond strength of cp Ti and Ti2448 is decreased by thermal and mechanical cycling. PMID- 27266200 TI - [Correlation studies in goats about the membrane thickness and pressure of the maxillary and frontal sinuses]. AB - OBJECTIVE: This study aimed to explore the differences of membrane thickness and pressure on the paranasal sinus membrane in goats and analyze their causes. The results can provide theoretical basis and guidance for the issues of the maxillary sinus floor augmentation related to the membrane. METHODS: The membrane was cut into two sizes from every sinus membrane. The membrane was fixed in formalin to obtain tissue specimens for the membrane thickness study and pressure study. The correlation between the two parameters was then analyzed, and appropriate statistical methods and software were selected. RESULTS: The top of maxillary sinus, the bottom of maxillary sinus and the frontal sinus membrane thickness were (410.03 +/- 65.97), (461.33 +/- 91.37), (216.90 +/- 46.47) um. The pressure were (260.08 +/- 80.12), (306.90 +/- 94.37), (121.72 +/- 31.72) kPa. The mean differences of the membrane thickness between the top of the maxillary sinus and the frontal sinus, bottom and frontal, and top and bottom were statistically significant (P < 0.05). The mean differences in membrane pressure were also statistically significant (P < 0.05). CONCLUSION: The membrane thickness and pressure of the top and bottom of the maxillary sinus are higher than those of the frontal sinus membrane. However, the thickness and pressure of the bottom membrane are slightly higher than those of the top membrane. Pressure and membrane thickness are positively correlated in the sinus membrane. PMID- 27266201 TI - [Influence of different designs and porcelain/glaze firing on the marginal and internal fit of implant-supported zirconia crowns]. AB - OBJECTIVE: This study investigated the influence of different designs and porcelain/glaze firing on the marginal and internal fit of three kinds of computer aided design/computer aided manufacturing (CAD/CAM) zirconia ceramic implant-supported crowns. METHODS: Three groups of zirconia ceramic implant supported crowns with different designs were produced from copings by using a Cercon CAD/CAM system (n = 8). The first two groups comprised double-layer crowns (zirconia coping + veneer) with regular (Group A) and full circumferential zirconia-collar marginal designs (Group B). The third group was composed of anatomic single-layer zirconia crowns without cores (Group C). Initially, the marginal and internal gaps of the copings and crowns were individually replicated by light-body silicon and then measured by micro-computed tomography scanning before and after porcelain/glaze firing. Five measurements were employed: vertical marginal gap (MG); horizontal marginal discrepancy (HMD); chamfer area (CA); axial wall (AW); and axial-occlusal transition area (AOT). Statistical analyses were performed by SPSS 17.0. RESULTS: HMD measurements in Group A were statistically higher than those in Groups B and C (P < 0.05), regardless of whether the values were obtained before or after porcelain/glaze firing. By contrast, the HIMD measurements in Groups B and C showed no significant difference (P > 0.05). Moreover, no differences were noted in MG, CA, AW, and AOT among the three groups (P > 0.05). All the measurements in the three groups showed no significant change after porcelain/glaze firing (P > 0.05), except for MG in Group A, which significantly decreased (P < 0.05). CONCLUSION: The marginal fits of the double-layer crowns with full circumferential zirconia-collar and the anatomic single-layer zirconia crowns were superior to that of the double-layer crowns with regular margins. The MG of the crowns with regular margins was obviously influenced by porcelain firing. PMID- 27266202 TI - [Synthesis and characteristics of integrated bionic mandibular condylar scaffold]. AB - OBJECTIVE This study aims to construct a chitosan (CS)-polycaprolactone (PCL) hydroxyapatite (HA) composite biomimetic scaffold to replace condyle and to explore the tissue engineering applications of condylar. METHODS: A resin mold of the mandibular condyle was prepared by using rapid prototyping techniques. A mandibular condylar integrated biomimetic scaffold model was prepared by solution casting-ice Lek. PCL and CS were mixed at a ratio of 4:1. HA at quality ratios of 40%, 50%, 60%, and 70% was added to groups a, b, c, and d, respectively. The microscopic morphology, porosity, infrared spectra, X-ray diffraction pattern, and mechanical properties of the scaffold were observed. RESULTS: The scaffold that includes both upper and lower parts displayed the same features (i.e., shape, yellow-white appearance, and hard texture) as the mandibular condyle. Scanning electron microscopy showed that the composite scaffold had a 3D network spatial structure, 70%-85% porosity, and 10-200 um pore size. Infrared spectra showed that the peak intensity reduced with decreasing HA content. X-ray diffraction showed that the diffraction peak decreased with increasing HA content. Suitable tensile and compressive and flexural strength were discovered in the presence of 50% HA. CONCLUSION: The scaffold prepared by solution casting ice Lek shows favorable comprehensive features and is expected to replace human condylar. PMID- 27266203 TI - [Collagen structure and biomechanical properties of the goat temporomandibular joint disc]. AB - OBJECTIVE: To establish objectively biomechanical criteria for temporomandibular joint disc tissue engineerings. METHODS: Eight temporomandibular joint discs from a four-month-old goat were separated completely. A cylindrical sample with diameter of 3 mm in the anterior, intermediate, and posterior bands was obtained, and the samples underwent pre-compression test with three cycles under a speed of 0.025 mm . s-1. With the end condition for the maximum load of less than 4.9 N and 1.5 mm compression displacement, the formal compression test was performed with the same speed. Moreover, this test obtained the stress-strain relationship and elastic modulus of each disc band. Ultrastructure and collagen fiber orientation of the district zone were observed by scanning electron microscope and polarized light microscope. RESULTS: 1) The physiological strain range of an articular disc was within 10%, and the quasilinear constitutive equation of articular disc tissues can be fitted with the polynomial function: y = ax + bx2 + cx3. 2) The elastic modulus of the intermediate disc zone was the largest (P < 0.05). No significant difference existed between the anterior and posterior bands (P = 0.361). 3) Scanning electron microscope and polarized light microscope showed an annular disc collagen network structure, which was the internal part of the goat temporomandibular joint disc. The collagen arrangement of intermediate bands was tensely arranged anterior-posteriorly. The collagen of anterior and posterior bands went through mediolaterally with intersection of anterior posterior branch fibersd. CONCLUSION: Annular collagen network structure is the basis for goat temporomandibular joint disc compression resistance properties. The intermediate band demonstrated higher compression resistance performance than the anterior and posterior bands. PMID- 27266204 TI - [Morphometric evaluation of changes in the alveolar bone of adolescents with bimaxillary protrusion via cone beam computed tomography]. AB - OBJECTIVE: This study aimed to evaluate the morphometric changes in the alveolar bone of the maxillary and mandibular anterior regions after retraction in adolescents. METHODS: The sample size comprised 30 adolescent patients with class 1 bimaxillary protrusion (12 males and 18 females, age: 12-18 years old) and were treated by extracting four first pre-molars. Cone beam computed tomography (CBCT) was performed 1 month before and 1 month after the retraction. For each maxillary and mandibular anterior tooth, the labial and palatal alveolar plates at cervical 1/3, middle 1/3, and apical 1/3 levels for bone thickness changes during the retraction of the maxillary and mandibular anterior regions were checked. The movements of cervical 1/3, middle 1/3, and apical 1/3 levels of the maxillary central incisor were measured. Statistical analyses were performed with SPSS 16.0. RESULTS: For the adolescents, alveolar bone thickness increased on the labial side and decreased on the palatal side. The alveolar bone thicknesses of cervical 1/3 and middle 1/3 of maxillary central incisor, cervical 1/3 and apical 1/3 of maxillary lateral incisor, middle 1/3 of mandibular central incisor, apical 1/3 of mandibular lateral incisor, and middle 1/3 and apical 1/3 of mandibular canine all increased after retraction. By contrast, the alveolar bone thickness of the apical 1/3 of maxillary canine and the cervical 1/3 of mandibular canine decreased after retraction. No statistically significant difference was observed in other region. CONCLUSION: During retraction, a controlled tipping movement occur in adolescents. After retraction, the alveolar bone thickness of the labial side increase, whereas that of the palatal side decrease. Moreover, the thicknesses of major areas in the alveolar bone significantly increase. PMID- 27266205 TI - [Anatomical presentation of edentulous sites in the posterior maxillary in cone beam computed tomography]. AB - OBJECTIVE: This study aimed to analyze the bone anatomy of edentulous sites in the posterior maxillary by cone beam computed tomography (CBCT). METHODS: A total of 100 CBCT radiographs from patients with missing maxillary posterior teeth were obtained, resulting in a sample size of 217 edentulous sites. The width and height of edentulous were assessed by three-dimensional reconstruction. In addition, the angle A and morphology of the maxillary sinus walls were evaluated. RESULTS: The mean bone height was 9.53 mm, and the percentage of sites than 10 mm was 62.67% (136/217). The mean bone width was 9.30 mm, and the percentage of sites more than 6 mm was 91.71% (199/217). The bone height decreased from premolar to molar areas, but the opposite trend was observed in bone width. Regarding the morphology of the sinus floor, 64.52% exhibited an oblique configuration. In angle A, the group of less than 30 degrees was 10.14%, 30 degrees -60 degrees was 42.40%, and greater than 60 degrees was 47.47%. CONCLUSION: A high percentage of edentulous sites in the posterior maxillary requires sinus floor elevation to allow the placement of dental implants. Thus, the use of CBCT scans is recommended to evaluate the anatomical structure of the maxillary sinus for reasonable implant planning. PMID- 27266206 TI - [Progress on space oral medicine research under microgravity environment]. AB - As an interdisciplinary of stomatology and space medicine, space oral medicine focuses mainly on oral diseases happened under space environment. With the manned space technology stepping into the new era, space oral medicine has been put under the spotlight. This article will review the historical events on this subject, summarize the newly progress especially on craniomaxillofacial bone, tooth-derived stem cell and oral microbiology researches and still put forward future prospect. PMID- 27266207 TI - [Correlation between pathogen-associated molecular patterns and periodontitis]. AB - Pathogen-associated molecular patterns (PAMPs) are conservative molecules associated with groups of pathogens or their products. These molecules are recognized by relevant receptors. PAMPs induce the expression of inflammatory cytokines through the signal cascade. The role of PAMPs in the initiation and development of periodontitis is recently attracting attention. PAMPs induce the expression of inflammatory mediators after they are recognized in the periodontium. This process damages the periodontal soft tissue and osseous tissue, thus resulting in periodontitis. The results of this study will provide an excellent resolution for the treatment of periodontitis by blocking the pathogenic pathway of PAMPs. PMID- 27266208 TI - [Mandibular ossifying fibroma and compound odontoma: a case report]. AB - A case diagnosed as ossifying fibroma and compound odontoma in the mandible was reported. The clinicopathological features, diagnosis, and treatment were discussed with the literature review. PMID- 27266209 TI - [Calcifying epithelial odontogenic tumor: two cases report]. AB - Calcifying epithelial odontogenic tumor (CEOT) is a rare benign epithelial tumor of odontogenic origin. CEOT is a benign but a locally infiltrative tumor. CEOT has two clinical variants: intraosseous (central) CEOT and extraosseous (peripheral) CEOT. The peripheral type is rare. In this paper, we report two cases of CEOT. The diagnoses of the cases were verified by histopathology. This study aims to explore the clinical and imaging appearances of CEOT and improve the understanding of the disease. PMID- 27266210 TI - Bone Mineral Density and Renal Function in Chronic Hepatitis B Patients Receiving Nucleotide versus Nucleoside Analogs: A Pilot Prospective Study. AB - BACKGROUND: The use of nucleotide analogs (NTAs) can be associated with negative effects on renal function and bone mineral density (BMD) due to proximal tubular dysfunction and hypophosphatemia; however, prospective data assessing the bone and renal safety of these agents are limited. OBJECTIVE: This study aimed to evaluate the prevalence of bone diseases among chronic hepatitis B (CHB) patients without cirrhosis and the changes in BMD and glomerular filtration rate (GFR) between patients receiving NTAs versus nucleoside analogs (NSAs). MATERIAL AND METHOD: We prospectively collected data from non-cirrhotic CHB patients who had been treated for < 1 year in Rajavithi Hospital (Bangkok, Thailand) between 2012 and 2014. Patients with significant comorbidities or those being treated for bone diseases were excluded. BMD assessment was performed at the lumbar spine (LS) and femoral neck (FN). BMD T-scores were used to define osteopenia (-2.5 to -1) and osteoporosis (< -2.5), and the GFR was estimated using the Cockcroft-Gault method. RESULTS: Twenty patients were included: 65% were men; 40% were HBeAg positive; and the median age was 42.7 (25.6-64.2) years. Ten patients had been treated with NTAs (7 with tenofovir 3 with adefovir) and 10 patients had been treated with NSAs (8 with lamivudine, 2 with entecavir), with a median follow-up period of 1.5 years (1.2-1.6). At baseline, the overall prevalence of osteopenia was 45% and the median GFR was 94 (51-144) mL/min. BMD in CHB patients was slightly lower than in an age-matched population based on Z-scores. Changes in LS BMD and FN-BMD were not significantly different between groups. The annual reduction in GFR was more pronounced in the NTA group (-7.4% vs. -1.39%, p = 0.018). CONCLUSION: Osteopenia is common in CHB patients without cirrhosis. Changes in BMD were not significantly different between groups. The annual reduction in GFR was more pronounced in the NTA group. PMID- 27266211 TI - Effects of Radiation Therapy on Immunological and Virological Status in HIV Infected Cancer Patients in Thailand: A Multicenter Prospective Study. AB - BACKGROUND: Radiation therapy (RT) is the core part of cancer multidisciplinary management which causes myelosuppression. The current standard or RT among HIV positive cancer patients who are immuno-compromised does not differ from that of HIV-negative ones. OBJECTIVE: To determine the effects of radiation therapy on immunological and virological status among HIV-infected cancer patients. MATERIAL AND METHOD: A prospective observational study was conducted of HIV-infected cancer patients who received definitive RT in seven hospitals in Thailand. Blood samples were taken to determine immune status using CD4%, and virological status was identified using plasma HIV-RNA viral load (HIV-VL) assay: at baseline before RT at the last week of RT completion; and at the 6-month follow-up visit. Additional CD4% test was performed at the 3-month follow-up visit. RESULTS: Ninety HIV-infected cancer patients from seven hospitals in Thailand were included in the analysis. The median age was 40 years old (range 19-61). Seventy six patients (84.4%) were female and 65 (72.2%) were cases of invasive cervical cancers. Eighty-seven percent of patients had been receiving antiretroviral treatment (ART) before RT The mean CD4% at baseline, RT completion, 3-month and 6 month follow-up visits, were 18.7%, 20.1%, 16.8% and 17.1%, respectively. The proportion of CD4% reduction in the non-ART group was higher than that of the ART group throughout the period, particularly at the 3-month follow-up visit (100% vs. 29.7%, p = 0.0004). Six cases had a HIV-VL increase of more than 10 times (1 log10) at completion of RT: 3 of these were non-ART and 3 were ART-uncontrolled viral suppression. CONCLUSION: RT had a suppressive effect on immunological status in HIV-infected cancer patients, particularly in the subacute period among those who were not on ART HIV-disease progression was observed during radiation treatment in HIV-infected cancer patients without ART and those with ART uncontrolled viral suppression. PMID- 27266212 TI - A 10-Year Clinical Experience of Gestational Trophoblastic Disease at Rajavithi Hospital, 2001-2010. AB - BACKGROUND: Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization and is categorized as either an hydatidiform mole (HM) or a gestational trophoblastic neoplasia (GTN). OBJECTIVE: To analyze the clinical characteristics, incidence and treatment outcomes of GTD at Rajavithi Hospital. MATERIAL AND METHOD: Medical records of women diagnosed with GTD at Rajavithi Hospital from January 1, 2001 to December 31, 2010 were retrospectively reviewed. Disease diagnosis, treatment and follow-up data were analyzed. RESULTS: A total of 329 cases of GTD were reviewed. HM was diagnosed in 167 patients (incidence 2.32 per 1,000 deliveries); 26 patients were lost to follow-up; and 49 of the remaining 141 patients (34.8%) developed post-molar GTN. In multivariable analysis, uterus >16 week size and pre treatment human chorionic gonadotropin (hCG) level >250,000 mIU/mL were the significant risk factors for developing post-molar GTN. Of 162 patients with GTN (incidence 2.25 per 1,000 deliveries), 15 patients were lost to follow-up, and 116 patients, 29 patients and 2 patients were classified as having low-risk GTN, high-risk GTN and placental site trophoblastic disease respectively. The overall survival rate in the low-risk group was 100% whereas in the high-risk group it was 86.2%. A modified WHO prognostic score of more than five was the significant risk factor for developing resistant GTN. CONCLUSION: GTD treatment at Rajavithi Hospital showed excellent clinical outcomes. Uterus >16 weeks size and pre- treatment hCG > 250,000 mIU/mL were the significant risk factors for developing post-molar GTN in HM patients. Classifying GTN patients into low- and high-risk groups was useful in planning treatment and counseling. PMID- 27266213 TI - Prevalence of Hemoglobin Cycling and Its Clinical Impact on Outcomes in Thai End Stage Renal Disease Patients Treated with Hemodialysis and Erythropoiesis Stimulating Agent. AB - BACKGROUND: Erythropoiesis-stimulating agent (ESA) treatment is the optimal therapy for anemia in end-stage renal disease (ESRD) patients receiving hemodialysis. During treatment with ESA, the level of hemoglobin usually fluctuates widely; this phenomenon is known as "hemoglobin cycling" and may be associated with higher rates of mortality. OBJECTIVE: To estimate the prevalence of hemoglobin cycling in Thai ESRD patients treated with chronic maintenance hemodialysis and ESA, to assess its clinical impact on patient outcomes, and to identify the associated risk factors for hemoglobin cycling occurrence. MATERIAL AND METHOD: An analytic retrospective study was conducted of 150 patients on chronic hemodialysis who were treated with ESA at Rajavithi Hospital and the Kidney Foundation of Thailand at Priest ' Hospital between January 2008 and December 2010. Hemoglobin cycling was defined as hemoglobin variability over a period of at least 8 weeks and amplitude of more than 1.5 g/dl. RESULTS: Hemoglobin cycling was experienced by 90.7% of patients. The mean amplitude was 2.4 +/- 0.7 g/dl and mean duration of hemoglobin cycling was 8.5 +/- 5.0 weeks. Most patients (34.7%) experienced two episodes. The mean level of hemoglobin in patients with hemoglobin cycling (gr. I) and those without it (gr. II) were 10.1 +/- 0.9 g/dl and 10.2 +/- 0.7 g/dl respectively (p = 0.60). The mortality and hospitalization rates in gr I and II were not significantly different (OR = 2.52; 95% CI: 0.31-20.27, p = 0.70 and OR = 1.65; 95% CI: 0.43-6.18, p = 0.56 respectively), and the numbers of ESA dose adjustments in gr. I and gr. II were also not significantly different (7.2 +/- 2.4 vs. 8.2 +/- 1.7 dose change/patient/year p = 0.14). The serum levels of blood urea nitrogen, creatinine, intact parathyroid hormone, ferritin, % transferrin saturation, weekly Kt/V urea and co-morbidity (diabetes mellitus, congestive heart failure, cerebrovascular disease and hypertension) were not significantly different in the two groups of patients. CONCLUSION: Hemoglobin cycling was commonly found in Thai ESRD patients treated with hemodialysis and ESA. The influence of hemoglobin cycling on mortality and hospitalization rates could not be significantly demonstrated in the present study; however both mortality and hospitalization rates showed an upward trend in patients with hemoglobin cycling. PMID- 27266214 TI - Presence of Sperm in Pre-Ejaculatory Fluid of Healthy Males. AB - BACKGROUND: Coitus interruptus, a common contraceptive method, has a high failure rate. Two reasons have been proposed for this: delayed withdrawal after ejaculation and presence of sperm in the pre-ejaculatory fluid. OBJECTIVE: To determine whether sperm was present in the pre-ejaculatory fluid of healthy males. MATERIAL AND METHOD: A total of 42 healthy Thai men were enrolled in the study between August 1, 2009 and November 30, 2009 at the Department of Obstetrics and Gynecology, Rajavithi Hospital. They were asked to collect pre ejaculatory fluid smears in two glass slides and then deposit a semen sample in a plastic bottle after masturbation. Microscopic examination of wet and air-dried preparations and routine semen analyses were done consecutively in the human genetics laboratory. RESULTS: Actively mobile sperm were found in 16.7% (7/42 cases) of the pre-ejaculatory penile secretions of subjects whose sperm counts were 2 in 2 cases, 3 in 3 cases and 4 per high power field in the other 2 cases of positive sperm. Semen analyses were normal in 41/42 volunteers (97.6%); there was one case of oligospermia (14 x 106/ml). CONCLUSION: Actively mobile sperm were discovered in the pre-ejaculatory fluid of 16.7% of healthy men. PMID- 27266216 TI - Nutritional Status and its Impact on Clinical Outcomes for Patients Admitted to Hospital with Cirrhosis. AB - BACKGROUND: In patients with cirrhosis, nutritional status is an important predictor of clinical outcomes that can be assessed in clinical practice using conventional methods. Previous studies have shown that malnutrition is associated with increased morbidity and mortality in patients with cirrhosis. However, there have been very few reports from Southeast Asia. OBJECTIVE: To determine the prevalence of malnutrition in patients with cirrhosis who are admitted to hospital and to assess its correlation with mortality, complications, length of stay, and total cost of hospitalization. MATERIAL AND METHOD: This prospective non-interventional study included 60 consecutive patients with cirrhosis admitted to Rajavithi Hospital, Bangkok, Thailand, from August 2013 to February 2014. Baseline demographic and clinical data during their hospitalizations were collected prospectively. Nutritional status was assessed by subjective global assessment (SGA) and anthropometry (body mass index (BMI) and mid-arm circumference (MAC)). Malnutrition was defined as SGA class B/ C and MAC of < 5th percentile of the age- and gender-matched reference population. RESULTS: Of the 60 patients, 70% were male. The most common causes of cirrhosis were alcohol (50%) and hepatitis C infection (35%). Most patients were classified as Child Pugh class B (41.7%) or C (36.7%). The mortality rate was 26.7%, and the most common complications were infections (60%) and renal failure (43.3%). The median length of stay in hospital was 8.5 (1-51) days, with a median cost of 1,163 (183 9,969) US dollars. The prevalence of malnutrition varied between 18% and 92% depending on the assessment method employed: 18% were considered malnourished when assessed by BMI, 63% by MAC, 78% by serum albumin, 65% by absolute lymphocyte count, and 92% by SGA. Patients with malnutrition showed a trend toward increased mortality, complications, length of hospital stay and cost; however, the differences were not statistically significant. Significant predictors of mortality included Child-Pugh class B (16% mortality) and C (50% mortality), severe malnutrition as assessed by SGA (35% mortality), presence of ascites (relative risk, RR: 2.3), hepatic encephalopathy (RR: 2.5), hepatorenal syndrome (RR: 4.1) and renal failure (RR: 3.3). CONCLUSION: Malnutrition is common in hospitalized patients with cirrhosis, and patients with malnutrition showed a trend toward increased complications and mortality. Severe malnutrition, as identified by SGA, and advanced cirrhosis were predictors of in-hospital mortality. PMID- 27266215 TI - Optimal Fasting Time before Measurement of Serum Triglyceride Levels in Healthy Volunteers. AB - BACKGROUND: Coronary heart disease is a major public health problem. Elevated triglyceride levels are a risk factor for atherosclerosis and coronary heart disease. Food intake interferes with the measurement of serum triglyceride levels, and in previous studies, fasting for 12 hours was recommended before blood sampling. In real-world practice, long fasting times cause patient discomfort and poor compliance, and the present study was, therefore, designed to determine the appropriate fasting time prior to measuring serum triglyceride levels. OBJECTIVE: To determine the appropriate fasting time before measuring serum triglyceride levels. MATERIAL AND METHOD: This was a pilot study performed using healthy volunteers aged between 20 and 30 years old from November 2013 to December 2013 at Rajavithi Hospital. The first blood sample was measured in the morning after fasting over 12 hours. The subjects then took their regular breakfast, after which they fasted for 8 hours. Blood samples were taken 6 and 8 hours later and sent to the laboratory for measurement of serum triglyceride levels. RESULTS: 40 volunteers, of whom 25 were female, were enrolled. Their mean age was 25.9 +/- 2.81 years old, and their mean weight, height, and body mass index were 61.5 +/- 12.5 kg, 167.2 +/- 8.3 cm and 21.84 +/- 3.1 kg/m2, respectively. Mean fasting serum triglyceride level at 12 hours was 80.23 +/- 36.33 mg/dl, at 6 hours it was 110.65 +/- 73.45 mg/dl, and at 8 hours it was 75.62 +/- 46.81 mg/dl. The group fasting for 12 hours had significantly lower serum triglyceride levels than the group fasting for 6 hours (p-value = 0.003), but no significant difference was found between the group fasting for 12 hours and the one fasting for 8 hours (p-value = 0.493). CONCLUSION: The present study showed no significant difference in triglyceride levels in patients who had fasted or 8 hours and those who had done so for 12 hours. Fasting for only 8 hours before measurement of serum triglyceride may be sufficient. PMID- 27266217 TI - A Comparison of the Efficacy and Renal Side Effects of Antihypertensive Drugs "Angiotensin Receptor Blockers" (ARBs) in Rajavithi Hospital. AB - BACKGROUND: Hypertension is a major public health problem. As a result of the enforcement of measures announced by the National Drug Committee, the majority of original drugs is no longer prescribed and is replaced with drugs in the national list of essential medicines. Patients originally taking Angiotensin receptor blockers (ARBs) frequently have their prescription changed to generic losartan. Only a few studies have been conducted in Thailand to compare the efficacy and renal side effects of original and generic drugs. OBJECTIVE: To compare blood pressure (both systolic and diastolic) of patients who were changed to losartan from other ARBs. MATERIAL AND METHOD: A retrospective cross-sectional study was carried out, collecting data from medical records of patients with hypertension who were prescribed losartan instead of other ARBs in Rajavithi Hospital from 1 January 2009 to 31 December 2014. One hundred patients with hypertension during this period were enrolled, and the drugs' relative efficacies in controlling blood pressure were compared, together with their renal side effects. RESULTS: The study enrolled 100 patients, of which 35% were men, and the mean age was 66.88 +/- 10.93 years. The average systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after changing from other A RBs to losartan showed a significant difference (134.16 +/- 12.89 vs. 140.92 +/- 11.76 mmHg, p value < 0.001) and (74.22 +/- 8.05 vs. 76.52 +/- 8.88 mmHg, p-value = 0.001, respectively). Other ARBs controlled hypertension significantly better than losartan (70.0% vs. 32.0%, p-value <0.001). Serum creatinine was significantly higher after changing the blood pressure lowering regimen (0.9 7 +/- 0.3 7 vs. 1.00 +/- 0.3 7 mg/dl, p-value = 0.047), but serum potassium levels did not change (4.27 +/- 0.40 vs. 4.27 +/- 0.32 mEq/L, p-value = 0.888). CONCLUSION: Original A RBs controlled hypertension significantly better than losartan. Serum creatinine levels were lower when A RBs were prescribed rather than losartan; however, serum potassium levels were not affected. PMID- 27266218 TI - Procalcitonin under Investigation as a Means of Detecting Severe Sepsis, Septic Shock and Bacteremia at Emergency Department, Rajavithi Hospital. AB - BACKGROUND: Severe sepsis, septic shock and bacteremia are critical illnesses, and patients with these conditions require close monitoring and immediate medical treatment. Any delay in diagnosis may lead to an increase in mortality in such critically ill patients. Serum procalcitonin (PCT) has emerged as a highly accurate biomarker for differentiating sepsis from other non-infectious triggers. OBJECTIVE: In this study, we investigated the effectiveness of PCT in obtaining early diagnosis and efficient prognosis for such patients at the Emergency Department of Rajavithi Hospital. MATERIAL AND METHOD: A prospective study was performed of 110 adult patients who attended the emergency service department between August 1 2013 and October 31 2013. The effectiveness of PCT as a specific blood test analysis tool for detecting and classifying the severity of patients with sepsis was investigated, and sensitivity, specificity, negative predictive values (NPV), positive predictive values (PPV) and positive likelihood ratio (LR+) were used to differentiate infected patients. RESULTS: One hundred and ten patients were enrolled and classified into 3 categories as follows: severe sepsis (n = 34, 30.9%), septic shock (n = 13, 11.8%), and bacteremia (n = 23, 20.9%). At a PCT level of >= 2 ng/dL, it was feasible to categorize patients as having severe sepsis (p < 0.001; RR 3.58; 95% CI 2.18-5.89), septic shock (p = 0.001; 5.73; 2.06- 15.93) or bacteremia (p < 0.001; 3.91; 1.98-7.73). Moreover, the PCT value yielded the following diagnostic performances for patients with: severe sepsis (PPV 70.8%; NPV 80.2%; LR+ 5.0; sensitivity 50.0%; specificity 90.8%); septic shock (33.3%; 94.2%; 3.6; 61.5%; 83.5%); and bacteremia (50.0%; 87.2%; 3.7; 52.2%; 86.2%). CONCLUSION: PCT can be usefully employed as a promising chemical biomarker to differentiate the severity of infections in critically ill patients. Used together with clinical data, the PCT value of >= 2 ng/dL is efficient in categorizing such patients as having severe sepsis, septic shock or bacteremia. PMID- 27266219 TI - Comparison of Endoanal Ultrasound with Clinical Diagnosis in Anal Fistula Assessment. AB - BACKGROUND: Anal fistula anatomy and its relationship with anal sphincters are important factors influencing the results of surgical management. Pre-operative definitions of fistulous track(s) and the internal opening play a primary role in minimizing damage to the sphincters and recurrence of the fistula. OBJECTIVE: To evaluate the relative accuracy of digital examination and endoanal ultrasound for pre-operative assessment of anal fistula by comparing operative findings. MATERIAL AND METHOD: A retrospective review was conducted of all patients with anal fistula admitted to the surgical unit between May 2008 and May 2012. Physical examination and hydrogen peroxide-enhanced endoanal ultrasound (utilising a 10 MHz endoprobe, HITACHI: EUB-7500), were performed in 142 consecutive patients. Results were matched with surgical features to establish their accuracy in preoperative anal fistula assessment. RESULTS: A total of 142 patients (107 men, 35 women), 28 of whom had had previous surgery, were included in the study. Their mean age was 40 (range 18-71) years and their mean BMI was 26.37 (range 17.30-36.11) kg/m2. The majority of the fistulas were transphincteric (90.4%) and the rest were intersphincteric (9.6%). The accuracy rates of clinical examination and endoanal ultrasound were 55.63 and 95.07 percent (p < 0.01), respectively. CONCLUSION: Endoanal ultrasound is superior to digital examination for pre-operative classification of anal fistula PMID- 27266220 TI - Comparative Survival Outcomes of Uterine Papillary Serous Carcinoma, Clear Cell Carcinoma, Grade 3 Endometrioid Adenocarcinoma, and Carcinosarcoma of Endometrial Cancer in Rajavithi Hospital. AB - BACKGROUND: Uterine papillary serous carcinoma (UPSC), clear cell carcinoma (CC), grade 3 endometrioid adenocarcinoma (G3EC), and carcinosarcoma (CS) have been identified as high-grade endometrial cancers and account for the majority of uterine cancer deaths. OBJECTIVE: To compare survival outcomes of patients with UPSC, CC, G3EC and CS in Rajavithi Hospital. MATERIAL AND METHOD: A retrospective review was performed of all patients with FIGO stage I-IV endometrial cancer in Rajavithi Hospital between 1 January 2007 and 31 December 2012. Kaplan-Meier estimates were made of overall survival (OS) and progression-free survival (PFS), and log-rank tests were used to compare survival distributions between histological subtypes. Cox regression was used to estimate hazard ratios for histological subtypes, adjusted for other significant prognostic factors. RESULTS: One hundred sixty-three patients had confirmed diagnosis of high-grade endometrial cancer: 45 had UPSC, 30 had CC; 58 had G3EC; and 30 had CS. The median age distribution of the four groups of patients was approximately 60 years. The body mass index, underlying disease, and parity were similar in each group. All patients underwent a hysterectomy and surgical staging procedure. The 2-year progression-free survival was poorest in the CS cases (79.4%), followed by CC (87.2%), G3EC (92.2%), and UPSC cases (95.5%), and these figures were statistically significantly different among the groups (p = 0.015). The 2-year overall survival was poorest in the CC cases (70.0%), followed by CS (76.7%), UPSC (86.7%), and G3EC (87.9%); however, there were no significant differences among the groups (p = 0.071). In multivariate analysis for OS, advanced stage and suboptimal surgery were significantly associated with increased risk of death. For PFS, advanced stage and positive peritoneal cytology were significantly associated with increased risk of recurrence. CONCLUSION: CS patients had a significantly lower rate of progression-free survival than other subtypes. These findings should be taken into account when considering counseling, primary treatment and appropriate adjuvant treatment in order to improve survival outcomes in these high-risk patients. PMID- 27266221 TI - Self-Preferred Route of Delivery of Thai Obstetricians and Gynecologists. AB - BACKGROUND: The attitude of Obstetricians and Gynecologists (OB-GYNs) towards performing cesarean delivery on maternal request (CDMR) together with their preferred route of delivery for themselves or their wives is considered as important responsible factors of increasing cesarean delivery. OBJECTIVE: To assess the attitudes of Thai Obstetricians and Gynecologists with regard to their self-preferred route of delivery, willingness to perform cesarean delivery on maternal request, and associated factors. MATERIAL AND METHOD: From July 1, 2013 to September 30, 2013, a cross-sectional study was carried out of 1,950 members of The Royal Thai College of Obstetricians and Gynaecologists who were randomized before being sent mailed questionnaires. The questionnaires requested details of the OB-GYNs' demographic data and asked about their self-preferred route of delivery for themselves or their wives (in the case of male doctors) and their willingness to perform cesarean delivery on maternal request (CDMR). The questionnaires were returned via mail. RESULTS: Three hundred and seventy OB-GYNs (18.9%) completed and returned the questionnaires via mail. In a scenario of uncomplicated singleton cephalic presentation pregnancy at term, vaginal delivery was chosen as the most preferred route of delivery (68.9%). The significant associated factors for preferred cesarean delivery were male, age < 40 years, experience in practice as OB-GYN < 10 years and prior cesarean delivery. Many (53.2%) were willing to perform cesarean delivery on maternal request. CONCLUSION: Most Thai Obstetricians and Gynecologists (68.9%) preferred vaginal delivery for themselves or their wives, but many (53.2%) were willing to perform cesarean delivery on maternal request. PMID- 27266222 TI - Survival Rates of Concurrent Chemo-Radiation versus Radiation Alone in Locally Advanced, Unresectable Head and Neck Cancers: A Retrospective Cohort Study. AB - OBJECTIVE: To compare survival rates of concurrent chemo-radiation (CRT) and radiation (RT) alone in locally, advanced unresectable head and neck cancers and to assess factors associated with survival. MATERIAL AND METHOD: A retrospective cohort study was conducted of 165 patients treated for locally advanced unresectable head and neck cancers (Stage III, IV) at the Department of Radiation Oncology, Rajavithi Hospital, from 1 January 2011 to 31 December 2013. Patients were divided into two groups: in the first group, 68 patients received CRT and in the second, 97 patients received RT alone. The Cox proportional hazards model was used to assess the factors which had an impact on survival while controlling for known prognostic factors. The ethics committee of Rajavithi Hospital reviewed and approved this study. RESULTS: There was an overall survival (OS) rate of 1 year (1 year OS) in 27% of cases, and 2 years (2 years OS) in 15.4% of cases with a median overall survival rate of 7.63 months (7.63 OS) (95% CI 6.99-8.2 7). The mean follow-up time was 7.34 months with maximal follow-up time of 41.77 months and minimal follow-up time of 0.2 months (6 days). Patients who received chemotherapy had better overall survival rates than those who had no chemotherapy with 1 year OS of 52% vs. 9.5%, 2 years OS of 36.7% vs. 1.5%, and median OS of 13.17 vs. 5.4 months, p < 0.001. However, no significant difference for median survival was observed among three different chemotherapy regimens with median OS of 11-13 months but chemotherapy group had significant difference from no chemotherapy group with median OS of 5.40 months (4.59-6.21). CONCLUSION: Concurrent chemo-radiation (CRT) should be used as the standard treatment in patients who are medically fit. A Cisplatin or Carboplatin weekly regimen can be used as an alternative to a Cisplatin three-weekly regimen. Site of primary tumor N-stage, recurrent tumor, low RT dose (below 70 Gy), and co-morbidity (with impaired renal or liver function) are significant predictors of overall survival. PMID- 27266223 TI - Prevalence of Diabetic Foot Ulcers and Risk Classifications in Type 2 Diabetes Mellitus Patients at Rajavithi Hospital. AB - BACKGROUND: Diabetic foot ulcers are a major cause of non-traumatic lower limb amputation in patients with type 2 diabetes. In 2014, the Diabetes Association of Thailand issued new guidelines for classifying type 2 diabetes patients' levels of risk of developing foot ulcers, but no research on the prevalence of type 2 diabetes using these new classification criteria had been performed prior to the current study. OBJECTIVE: To study the prevalence of diabetic foot ulcers overall and in different risk groups in type 2 diabetes mellitus patients in Rajavithi Hospital, and to evaluate risk factors of these groups and correlations with ankle brachial index (ABI) and cardio-ankle vascular index (CAVI). MATERIAL AND METHOD: 593 type 2 diabetes patients at Rajavithi Hospital were studied and classified into risk groups based on the classification criteria issued by the Thailand Diabetes Association in 2014. ABI measurements were taken from 132 patients, and measurements of CAVI were taken from 101 patients. RESULTS: The prevalence of foot ulcers was 3.4% and 2.2% of patients had a history of amputation. The percentages of patients at low, intermediate and high risk of developing foot ulcers were 55.8%, 33.6% and 10.6%, respectively. Age, duration of diabetes, estimated glomerular filtration rate (eGFR), history of hypertension, dyslipidemia, nephropathy, cardiovascular disease (CVA), deformity of foot, numbness, abnormal protective sensation, pulse deficit, ulcer, and amputation were factors significantly associated with a high risk of foot ulcers (p < 0.05), but fasting plasma glucose (FPG) and HbA1c were not significant factors. There was an association between cerebrovascular accident and abnormal ABI. CONCLUSION: Nearly half of these type 2 diabetes patients were in the groups with an intermediate or high risk of developing foot ulcers. Screening of patients at risk of foot ulceration is necessary in order to classify patients into risk groups and provide appropriate education, as well as proper monitoring and management. PMID- 27266225 TI - Corneal Ulcer Leading to Evisceration or Enucleation in a Tertiary Eye Care Center in Thailand: Clinical and Microbiological Characteristics. AB - BACKGROUND: Very severe corneal infection can lead to permanent visual loss, and there is still inadequate knowledge about these severe cases. OBJECTIVE: To identify clinical and microbiological characteristics of corneal ulcers resulting in evisceration or enucleation in a tertiary eye care center in Thailand. MATERIAL AND METHOD: A retrospective chart review was performed of all patients who required evisceration or enucleation due to corneal ulcer at Rajavithi Hospital, Bangkok, Thailand between October 2008 and September 2013. RESULTS: One hundred patients who underwent evisceration or enucleation as a result of corneal ulcer were included in the study. The mean age of the patients was 56.5 +/- 12 years, most cases were referred from other hospitals (93%), and 13% of patients were diabetic. At presentation, visual acuity was worse than 5/200 in almost all cases (98%), and trauma (66%), especially by organic substances (36%), was the most common cause. Most cases had full thickness infiltration (81%) with mean size of 6.6 +/- 2 mm. Corneal perforation was found in 18% of patients at presentation, and 60% of corneal scraping cultures were positive. Bacteria were the most common pathogens (65%), leading by Pseudomonas aeruginosa (10 cases), and the most common fungus was Fusarium spp. (7 cases). Secondary glaucoma (39%) and corneal perforation (25%) were the main ocular complications. Over half of the patients (52%) needed therapeutic or tectonic surgical intervention during admission. Following evisceration (94%) or enucleation (6%), 23 cases had wound complications that required further surgical treatment. Bacterial infection was found to increase the risk of wound complications more than infection by other pathogen groups (40.9%, p = 0.013). CONCLUSION: Despite aggressive medical and surgical treatments, very severe corneal ulcers at referral can lead to loss of an eye. Bacterial infection, especially by Pseudomonas aeruginosa, following eye trauma was the most common cause. Evisceration in bacterial corneal ulcers had greater wound complications than ulcers infected by other pathogens. PMID- 27266224 TI - Differential Diagnosis between Primary Endocervical and Endometrial Adenocarcinoma using Immunohistochemical Staining of Estrogen Receptor, Vimentin, Carcinoembryonic Antigen and p16. AB - BACKGROUND: When clinical and histopathological evaluation is not effective in discriminating primary endocervical adenocarcinoma (ECAs) and endometrial adenocarcinoma (EMAs), an immunohistochemistry (IHC) method is regularly used in practice, which involves staining of estrogen receptor (ER), vimentin (Vim), monoclonal carcinoembryonic antigen (mCEA) and p16. OBJECTIVE: To evaluate the performance of IHC markers, ER, Vim, mCEA and p16, in differentiating between primary ECAs and EMAs and to compare the performances of two-, three- and four marker panels. MATERIAL AND METHOD: Women with cervical or uterine cancers who were diagnosed with mucinous or endometrioid adenocarcinoma or adenocarcinoma of non-otherwise specified, after cervical biopsy, endometrial biopsy or curettage, and who underwent elective surgery at Rajavithi Hospital between January 1, 2011 and June 30, 2012 were retrospectively reviewed. Paraffin-embedded tissue sections from pre-operative specimens were reviewed and stained with ER, Vim, mCEA and p16. Postoperative pathologic slides was reviewed and installed as the reference standard. RESULTS: Of 110 cases, 44 were primary ECAs and 66 were primary EMAs. ER and Vim were significantly expressed in EMAs (p < 0.001), while mCEA and p16 were significantly expressed in ECAs (p < 0.001). From multivariable analysis, Vim and p16 were the significant markers for differentiating ECAs and EMAs. A comparison of different combinations showed that panels of Vim/p16, ER/Vim/p16, Vim/mCEA/p16 and ER/Vim/mCEA/p16 achieved the highest overall accuracy of97.9%. CONCLUSION: Vim and p16 are the significant IHC markers and a two-marker panel of Vim/p16 is recommended for using in differentiating primary ECAs and EMAs; which a pattern of negative Vim and positive p16 expression favors diagnosis of ECAs while the converse pattern of positive Vim and negative p16 staining points to diagnosis of EMAs. PMID- 27266226 TI - Radioiodine (1-131) Dose for the Treatment of Hyperthyroidism in Rajavithi Hospital. AB - BACKGROUND: The main cause of hyperthyroidism is diffuse toxic goiter (Graves' disease), and the treatment of choice after medical therapy failure is radioiodine (I-131). There are two common methods of determining the optimal I 131 dose: calculated dose or fixed dose. The calculated dose method is based on the following formula: 75-200 microcuri/gram of thyroid gland divided by the percentage of radioiodine uptake at 24 hours (24-hour RAIU). As this is quite complex, some centers use fixed doses, such as 5, 10 or 15 mCi because it is simpler. At Rajavithi Hospital, the applied dose of I-131 is determined based on the thyroid gland weight assessed by palpation and other clinical factors. OBJECTIVE: To study the mean I-131 dose for the initial treatment of hyperthyroidism in Rajavithi Hospital, to find the clinical factors that correlate with I-131 treatment dose, and to devise a formula to predict the optimal I-131 treatment dose. MATERIAL AND METHOD: This was a retrospective study of 510 patients with a diagnosis of hyperthyroidism who received initial I-131 treatment at the Department of Nuclear Medicine in Rajavithi Hospital between January 2014 and June 2015. Baseline characteristics including age, sex, age at diagnosis, duration of antithyroid drug (ATD) therapy, gland weight (g), 3-hour RAIU and I-131 treatment dose were reviewed from medical records. RESULTS: The mean age +/- SD was 41.93 +/- 14.11 years (range 14-81 years), and the male to female ratio was 4.1:1. The mean duration of ATD therapy was 3.54 +/- 4.02 years (min-max, 0.8-40.6 years). The mean gland weight was 54.35 +/- 32.95 grams, and the mean 3-hour RAIU was 55.5 +/- 23.69%. The mean I-131 treatment dose was 14.84 +/- 5.71 mCi (min-max, 7-30 mCi). There was no significant correlation between dose and age, age at diagnosis, duration of A TD therapy or 3-hour RAIU. The study showed a significant correlation between I-131 dose and gland size, r = 0.938 (p < 0.001), and the regression relationship equation was: 1-131 dose = 0.235 gland size, r = 0.938. CONCLUSION: I-131 is the treatment of choice for hyperthyroidism after medical therapy failure, and there are various techniques for determining the optimal dose. At Rajavithi Hospital, the I-131 dose (mean = 14.84 +/- 5.71 mCi) is estimated based on the gland weight by palpation and other additional clinical factors. The present study provided a practical formula which is simple and practical for use in determining the I-131 dose for the treatment of hyperthyroidism: Dose of I-131 (mCi) = 0.235 x gland size (g). PMID- 27266227 TI - Positron Emission Mammography for Breast Cancer in Rajavithi Hospital. AB - BACKGROUND: Positron Emission Mammography (PEM) is a new modality in the investigation of breast cancer in Rajavithi Hospital, and its effectiveness has not yet been evaluated. OBJECTIVE: To study the effectiveness and characterization of breast images taken with PEM in Rajavithi Hospital. MATERIAL AND METHOD: This was a retrospective study in which data were collected and analyzed of patients who were investigated by PEM in Rajavithi Hospital between 18 September 2013 and 31 May 2014. Lesion to background (LTB) ratio of >_2. 0 with focal localization was considered to be suggestive of PEM positive for malignancy. RESULTS: Twenty-three female patients were included in the study, and their mean age was 51.7 years. Mean fasting blood glucose (FBS) was 93.64 mg/dl, and mean Fluorodeoxyglucose (FDG) injected dose was 7.76 mCi. The average PUV mean of background of both breasts decreased with advancing age. Fourteen patients were pathologically diagnosed with a total of lesions, of which 12 were malignant and four were benign. The positive predictive value (PPV) was 76.92%, and the mean LTB of true positive lesions was 5.31. Three false positive lesions were found: one mild atypical cell, one papilloma and one fibroadenoma, and the mean LTB was 2.92. The two false negative lesions were both DCIS. CONCLUSION: There was a moderate PPV in this PEM study for breast cancer in Rajavithi Hospital, and investigators need further experience and training in interpreting PEM. The information of mammographic, ultrasonographic and clinical findings should be used together with PEM to make diagnostic decision. The addition of biopsies could also improve the efficacy of PEM studies. PMID- 27266228 TI - Characteristics and Treatment Outcomes of Colonic Diverticulitis in Hospitalized Patients in Thailand. AB - BACKGROUND: Colonic diverticular disease exhibits mucosal outpouchings through the large intestine. Common complications of this disease are diverticular bleeding and diverticulitis. The prevalence of the disease is age-dependent, and some patients with diverticulitis develop complications especially the elderly, the obese and those with co-morbid diseases. In a retrospective study in Chiang Mai, Thailand, the mortality rate was 3.6% at 30 days and 9.2% at 1 year. OBJECTIVE: To determine the financial burden, clinical characteristics and factors associated with severity and mortality of patients with colonic diverticulitis. MATERIAL AND METHOD: This was a retrospective study of in patients from hospitals nationwide, and data were retrieved from three major health care system databases in the fiscal year 2010, searching for ICD code 10. Patients diagnosed with diverticular disease of the large intestine were included in this study, and baseline characteristics and clinical outcomes were analyzed. The study was approved by the institutional ethics committee of Rajavithi Hospital. RESULTS: One thousand seven hundred and fifty patients with colonic diverticulitis were enrolled in the study and their data were analyzed. The mean age of the patients was 61.15+16.12 years old, about 70% of patients had co morbid diseases, and the incidence of complicated colonic diverticulitis was 14.51%. The median length of hospital stay (LOS) was 6 days, half of the patients underwent surgery, and the mortality rate was 3.26%. Multivariate regression analysis revealed that the parameters associated with disease severity were number of co-morbid diseases, the universal coverage health care system, and surgical treatment, while the parameters associated with mortality were having more than two co-morbid diseases and being in the universal coverage health care system. CONCLUSION: Colonic diverticulitis was common in elderly patients and associated with co-morbid diseases. Most patients had mild severity but a high rate of surgery, and the mortality rate was higher than in western countries. Parameters associated with disease severity and mortality were having co-morbid disease, being in the universal coverage healthcare system and having surgical treatment. PMID- 27266229 TI - Efficacy of Plai Cream in Adult Patients with Muscle Strain: A Randomized, Double Blind, Placebo-Controlled Trial. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs are a standard treatment option for muscle strain; however, side effects persist. OBJECTIVE: This clinical trial was designed to compare the efficacy of Plai cream compared to placebos in adult patients with muscle strain. MATERIAL AND METHOD: In this randomized, double blind, placebo-controlled trial, 140 participants aged over 18 years with muscle strain were randomized to receive either Plai cream (n = 70 patients, treatment group) or placebos (n = 70 patients, control group) . Outcome assessments included the visual analog scale (VAS), quality of life (QoL), the amount of remaining cream, and the number of acetaminophen tablets used. RESULTS: After 2 weeks, the mean pain scores following treatment with both Plai cream and placebos in patients with muscle strain decreased from baseline to the end of the study at week 2. However, no significant difference for VA S score was found. The QoL of the two groups showed improvements in QoL as witnessed by increased mean QoL scores from baseline to week 2; however, these differences were not statistically significant. In general, mean QoL scores above 50 indicate good quality of life. The amount of Plai cream used reduced from baseline to week 2, but no significant difference in the amount of cream remaining was found between the two groups at each visit. Similarly, the number of acetaminophen tablets used was not statistically different between the treatment and control groups. CONCLUSION: There was no difference in pain reduction in the 2-week period between patients with muscle strain using Plai cream and those given placebos, but Plai cream tended to reduce pain in the long term. No side effects were found from Plai cream, so this non-invasive treatment may be offered to patients. PMID- 27266230 TI - Prevalence of Sexually Transmitted Infection in Teenage Pregnancy in Rajavithi Hospital, Thailand. AB - BACKGROUND: Behavioral and social changes in the modern era have triggered an increase in the incidence of early sexual contact and teenage pregnancy. Since there is no routine Gonococcal & Chlamydial (GC & CT) screening in teens in antenatal clinics in Thailand, the present study was performed to find the prevalence of STI, especially Chlamydial infection, in teenage pregnancy. OBJECTIVE: To evaluate the prevalence of sexually transmitted infections (STIs), especially Chlamydial infection (CT), in teenage pregnancy and its related factors. MATERIAL AND METHOD: One hundred and twenty-one teenage pregnancies were recruited at the ANC in Rajavithi Hospital from October 2006 to May 2007. After signing informed consent forms, they were asked to answer questionnaires about baseline data, sexual information and risk factors, after which urine specimens were collected for screening for GC and CT using the PCR technique (AMPLICOR by Roche). Later, pelvic examination was per formed by the gynecologist at the STD (sexually transmitted disease) clinic. All the data and LAB results were recorded and analyzed by the SPSS program. Numbers, percentages, means with SD, Chi squared test, Fisher's exact test and odds ratio were used. Potential risk factors were analyzed using binary logistic regression. RESULTS: The prevalence of STI in pregnant teenagers was 28.1% (CT = 19.8%, GC = 1.7%, hepatitis B = 3.3%, trichomoniasis 1.7%, Herpes simplex = 0.8% and condyloma acuminata = 0.8%). No Syphilis, chancroid or HIV were found in the present study Other non-STI like candidiasis and bacterial vaginosis were found in 45.5% of participants (candidiasis and bacterial vaginosis at 19.0% and 24.8%, respectively). The risk of CT infection was significantly related (6.9 times higher) to having previous sexual contact before the current partner (95% CI, 1.8-27.0). CONCLUSION: STI, especially Chlamydial infection, was found in a significant number of teenage pregnancies. Measures should be taken to prevent this resulting in complicated outcomes in the future. PMID- 27266231 TI - Factors Associated with Hospitalization of Chronic Obstructive Pulmonary Disease Patients with Acute Exacerbation in the Emergency Department, Rajavithi Hospital. AB - BACKGROUND: Chronic Obstructive Pulmonary Disease with acute exacerbation (AECOPD) is a condition, which frequently results in patients visiting the emergency department (ED). Recently, many studies have reported new factors, which cause AECOPD-patients (AECOPDs) to require urgent hospital admission. OBJECTIVE: To determine the crucial factors of AECOPDs that are associated with patients who visit the ED being admitted to Rajavithi Hospital. MATERIAL AND METHOD: This retrospective cross-sectional study was performed from May 1, 2011 to June 30, 2013. Seventy patients were included and their medical records were reviewed. A logistic regression model (SPSSv17) was used to analyze the prognostic factors associated with hospitalization. RESULTS: The study found that patients with a respiratory rate >24 breaths per minute (OR = 3.43; 95% CI = 1.10 10.84; p = 0.040), pulse rate >120 beats per minute (OR = 4.10; 95% CI = 1.31 12.74; p = 0.020), and oxygen saturation <90% (OR = 5.25; 95% CI = 1.20-23.00; p = 0.030), were prone to be admitted to the hospital. Furthermore, such patients more often required hospitalization if they had met any of the following criteria: had respiratory-infection related Global Initiative for Chronic Obstructive Lung Disease standard stages 3-4; were receiving home oxygen therapy; had an annual rate of ED visits of more than 2; had higher leukocytes; classified in the ED emergency triage as emergent; or who received antibiotics at the ED. CONCLUSION: Respiratory rate, heart rate and oxygen saturation are the crucial symptoms of AECOPDs to which physicians at ED should pay special attention. Such factors are reasonable indicators for hospitalization in order to reduce ED overcrowding. The study also found that patients treated early with antibiotics in the ED may be associated with subsequent hospitalization for ongoing management. However further studies are required for verification. PMID- 27266232 TI - Computer-Assisted Total Knee Arthroplasty vs. Conventional Total Knee Arthroplasty: Post-Operative Ankle Radiographic Findings and Ankle Clinical Assessment. AB - BACKGROUND: A number of previous studies have shown that conventional total knee arthroplasty (TKA) can affect talar tilt (TT) in the ankle of the operated leg. We aimed to prevent this problem by utilizing computer-assisted Total Knee Arthroplasty (CAS-TKA). OBJECTIVE: To compare pre- and post-operative talar tilt and ankle clinical assessment after computer-assisted total knee arthroplasty (CAS-TKA) and conventional total knee arthroplasty (TKA) in the 56 knees of 28 patients who underwent bilateral TKA. MATERIAL AND METHOD: We studied the 56 knees of 28 patients who underwent computer-assisted total knee arthroplasty (CAS TKA) in one knee and conventional total knee arthroplasty (TKA) in the other A combination of the Gap Balancing and Measured Resection techniques was used, and the operations were performed by a single surgeon. At follow-up 12 months post operatively, we examined ankle radiographic findings for tibio-talar angle (TTA), tibial articular surface angle (TAS), and talar tilt (TT) which was taken as the difference between TAS and TTA. Ankle clinical assessment was performed using the foot functional index (FF) in both groups pre- and post-operatively. The study also compared the results of computer-assisted total knee arthroplasty with those of conventional total knee arthroplasty pre- and post-operatively. RESULTS: We studied the 56 knees of 28 patients whose mean age was 67.79 years and who underwent bilateral total knee arthroplasty. Comparison of pre-operative and postoperative TT in the Conventional group showed a significant difference (p = 0.016), while there was no significant difference in the CAS group (p = 0.657). Ankle clinical assessment using foot functional index (FFI) revealed that there was no significant difference in the pre-operative FFI in the Conventional group = 1.85 (0.81, 6.88) and that of the CAS group = 1.91 (0.24, 66.5) (p = 0.577). The post-operative FFI in the Conventional group was 1.68 (0.24, 7.0) and in the CAS group it was 1.65 (0.24, 6.76), and these results were statistically significant (p = 0.047). In the Conventional group, the postoperative FFI was not significantly different from pre-operative FFI (p = 0.269), but in the CAS group there was a significant difference (p = 0.047). CONCLUSION: This study showed that conventional total knee arthroplasty affected postoperative talar tilt while computer-assisted total knee arthroplasty had a lesser effect and did not significantly change the axis of rotation of the ankle joint. More research needs to be carried out on larger numbers of patients with longer follow-up periods. PMID- 27266233 TI - Quality of Life Achieved by Carboplatin Plus Etoposide as Third-Line Chemotherapy Compared with Best Supportive Care in Non-Small Cell Lung Cancer Stage IIIB/IV. AB - BACKGROUND: Advanced stage (IIIB/IV) non-small cell lung cancers (NSCLC) are mostly treated with paclitaxel or gemcitabine combination chemotherapy as first line treatment and docetaxel as second-line therapy under the national reimbursement program, but there is no treatment specified for use after disease progression. New third-line chemotherapy drugs including new targeted therapies are expensive and bring about only slightly prolonged progression-free survival and minimally better response in healthy patients. OBJECTIVE: Carboplatin plus etoposide chemotherapy, which was formerly used as a low-cost first-line treatment, was used as third-line therapy for advanced NSCLC in order to compare its results with those of best supportive care as a treatment for improved quality of life (QoL) and progression-free survival. MATERIAL AND METHOD: This prospective study of advanced NSCLC stage IIIB/IV enrolled 47 patients receiving either third-line chemotherapy with carboplatin plus etoposide or best supportive care in the Oncology Unit, Medicine Department, Rajavithi Hospital from 1 January 2005 to 31 December 2012. Results of treatment and quality of life of the two groups (QoL) were evaluated using the Functional Assessment of Cancer Therapy Lung Cancer (FACT-L). RESULTS: The 47 advanced NSCLC patients were given either carboplatin plus etoposide chemotherapy (27 cases) or best supportive care (20 cases). No statistically significant differences were found in baseline characteristics and quality of life in the two groups. The median progression free survival after two months was significantly higher (88.9% vs. 75.0%, p-value < 0.001) in the chemotherapy group than in the best supportive care group, but no there were no statistically significant differences between QoL of patients in the two groups. CONCLUSION: Carboplatin plus etoposide as third-line chemotherapy regimen demonstrated higher median progression-free survival in advanced NSCLC patients and did not adversely affect QoL. PMID- 27266234 TI - Problems with Complete Dentures and Related Factors in Patients in Rajavithi Hospital from 2007 to 2012. AB - BACKGROUND: Complete dentures are used to restore masticatory function, improve esthetics, enhance phonetic functionality, and facilitate social communication for edentulous patients. After long-term use, problems can arise because of changes in the patients' condition and because of denture attrition. OBJECTIVE: To survey problems encountered while using complete dentures, and to evaluate related factors after 3-8 years of use. MATERIAL AND METHOD: One hundred and fourteen participants aged between 56 and 97 years who wore complete dentures supplied by Rajavithi Hospital between 2007 and 2012 were included in the survey. Data were collected via telephone interviews. Details were recorded for baseline characteristics of patients, how and when they used their dentures, how they maintained them, their perception of the condition of their dentures, and the problems that they encountered while using them. Descriptive statistics were used to evaluate patient characteristics and Chi-square/Fisher's exact/Student t-tests were used to evaluate correlations between condition of dentures and patient factors. A p-value of less than 0.05 was considered statistically significant. RESULTS: Half of all participants had problems in using complete dentures, and the most frequent difficulty was denture looseness, which affected about one third of all patients. Marital status, whether or not participants had children, and time of wearing dentures were significantly related to having problems (p = 0.007, 0.039, and 0.003, respectively). CONCLUSION: Many complete denture patients had problems with denture looseness and dentists should recall these patients in a timely manner to help them achieve a better quality of life. PMID- 27266235 TI - Trends of Metabolic Syndrome Components in Personnel at the Rajavithi Hospital. AB - OBJECTIVE: Metabolic syndrome (MetS) is a combination of medical disorders which increases the risk of developing diabetes. Studies have shown variable prevalence of this syndrome, but being elderly has often been found to increase the likelihood of developing Mets. This study aims to determine trends in Mets components among Rajavithi Hospital personnel. MATERIAL AND METHOD: A cross sectional study was carried out from 2009 to 2011. Participants were aged 35 years or more, and the numbers of participants were 504, 1,029 and 1,057 in 2009, 2010 and 2011, respectively. Using medical records after an annual check-up, MetS was defined in accordance with the updated National Cholesterol Educational Program Adult Treatment Panel III (NCEP-ATPIII) guideline. Binary logistic regression was used to assess the factors associated with Mets. RESULTS: Most participants were female, and the mean ages were 45.8 +/- 7.6, 45.6 +/- 7.9 and 46.1 +/- 7.1 years in 2009, 2010 and 2011, respectively. In each of the three years, mean age, BMI, waist circumference, triglycerides, glucose and uric acid were all significantly higher in individuals who had Mets. The prevalence of Mets in 2009, 2010 and 2011 was 7.1%, 5.9% and 4.6%, respectively. Hypertension was the most common abnormal metabolic risk factor in both sexes. The most frequent cluster of MetS components was a combination of hypertension, hypertriglyceridemia and glucose in males, but hypertension, abdominal obesity, and high triglyceride levels in females. The prevalence of MetS was associated with advancing age, male gender and individuals who worked in administration. CONCLUSION: The prevalence of Mets was low and decreased slightly each year. Associated risk factors of Mets were increasing age, male gender and working in administration. Some components of MetS, especially waist circumference, blood pressure, triglyceride levels and glucose, are risk factors of metabolic syndrome and should be avoided in order to decrease its prevalence. PMID- 27266236 TI - Characteristics and Demographic Distributions of Toxigenic Clostridium difficile Strains in Rajavithi Hospital, 2009-2015. AB - BACKGROUND: In recent years, toxigenic Clostridium difficile infection (CDI) has been the cause of C. difficile-associated diseases (CDAD), resulting in increasing hospitalization, community infection outbreak and mortality all over the world. OBJECTIVE: To investigate the prevalence of toxigenic C. difficile strains in Rajavithi Hospital. MATERIAL AND METHOD: This was a retrospective study of data from C. difficile toxin tests at Rajavithi Hospital's microbiology laboratory from January 1, 2009 to June 30, 2015. RESULTS: Of the 5,821 stool specimens tested for C. difficile toxin, 561 (9.6%) were positive for toxigenic C. difficile strains (10.2%, 7.6%, 5.6%, 9.6%, 9.7%, 15.4% and 12.0% respectively from year 2009 to 2015). The samples of all 453 unrepeated patients with this toxigenic C. difficile strain were analyzed. Two hundred and fifty-six (56.5%) of the patients were female, and the highest prevalence (58.3%) of toxigenic C. difficile strains was found in those aged over 65 years old. Overall, 7.7% of toxigenic C. difficile strains were isolated from OPD while the other 92.3% were from IPD. The majority of these strains (73.0%) were isolated in patients from the internal medicine wards, followed by surgery wards, intensive care units (ICUs), gynecology wards, radiation oncology wards and orthopedic wards at 8.9%, 6.2%, 2.4%, 2.2% and 1.1%, respectively. CONCLUSION: The prevalence of toxigenic C. difficile strains at Rajavithi Hospital was not high. The occurrence of these strains, recorded for each month of the study period, showed an irregular trend, but by far the highest frequency was found in older age groups. Rapid and accurate detection is necessary to enable immediate treatment and to stop the spread of infection. In future, these strains will be studied at a molecular level and antimicrobial susceptibility testing will be performed and the results entered in a database of toxigenic C. difficile strains in Thailand. PMID- 27266237 TI - Somatic HRPT2 Mutation (Arg234X) of Parathyroid Carcinoma Associated with Slipped Capital Femoral Epiphysis: A First Case Report. AB - A 14-year-old boy was admitted to the orthopedic clinic of Rajavithi Hospital complaining of pain in the left hip. A year earlier, pain had developed in his left joint and had gradually increased in intensity in both hips. A month before he was referred, radiographs obtained at another hospital showed bilateral slipped capital femoral epiphysis (SCFE). The patient's biochemical laboratory data showed hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone (iPTH) compatible with primary hyperparathyroidism. HRPT2 gene analysis found heterozygosity for c. 700 C > T mutation (Arg234X) of HRPT2 gene at exon 7. This is the first report in the literature about somatic mutation of the HRPT2 gene of parathyroid carcinoma associated with slipped capital femoral epiphysis. PMID- 27266238 TI - Neurological Recovery of Upper Extremity in Stroke Woman after 5 Years: A Case Report. AB - Strokes are common neurological disorders in Thailand. Rehabilitation programs significantly improve arm function outcomes if performed during the sub-acute period of stroke rehabilitation, within 6 months of the attack. This report describes the case of a stroke patient who gained upper extremity motor recovery after 5 years, which is beyond the normal recovery period. Although the patient does not have functionality, she has partial motor recovery, and she is enthusiastic about learning to gain better use of her hand. However there is still limited evidence to use in designing effective intervention and proper timing of rehabilitation administered by personnel in training chronic stroke patients. Therefore, evidence based on neuroplasticity and neurological recovery in chronic stroke patients, including rehabilitation intervention, is presented in this report. PMID- 27266239 TI - Five Synchronous Paragangliomas of the Head and Neck: A Case Report. AB - This is a case report of synchronous bilateral carotid body tumor, bilateral jugulotympanic and left subclavian paraganglioma in a 38-year-old man who presented with a history of slow-growing bilateral neck masses for 4 years and a one-month history of right facial palsy, tinnitus, and hearing loss. A discussion of this case is followed by a review of the literature surrounding this rare clinical entity. PMID- 27266240 TI - Bilateral Atrial Myxoma: A Case Report. AB - Among the rare cardiac tumors, myxoma, which is mostly located in the left atrium, is the most common type. Bilateral atrial myxoma is extremely rare, and requires urgent surgery. The authors report the case of a 34-year-old male, who presented with one month of right hemiparesis and aphasia and subsequently diagnosed with bilateral atrial myxoma based on transthoracic echocardiography. An urgent operation for intra-cardiac tumor removal was performed with the biatrial approach. Once a diagnosis of myxoma has been made, an urgent operation for tumor removal is necessary due to the risk of serious complications, including sudden death from normal blood flow obstruction. PMID- 27266241 TI - Cholesterol Granule of the Ethmoid Sinus: A Case Report. AB - Cholesterol granuloma (CG) is common in the mastoid air cells, less common in the skull base and orbit, and uncommon in the paranasal sinuses. The most commonly affected sinus is the maxillary sinus, and it is very rare in the ethmoid and sphenoid sinus. CG is thought to be due to impair the venous and lymphatic drainage from the sinus cavity. In the early period of the disease, the patient has no symptoms but when the expanding cysts compress the surrounding structures, they cause bony erosion that leads to clinical symptoms such as nasal blockage, eye pain or visual loss. If the patients' presentation does not correlate with physical examination, concerns are raised, and imaging should be performed. This study reports a case of cholesterol granuloma of the ethmoid sinus treated with the endoscopic marsupialization technique. This paper will remind physicians of the characteristics of cholesterol granuloma, which are useful for differential diagnosis of patients with this condition. In addition, it is the first reported case of cholesterol granuloma of the ethmoid sinus in the Thai literature. PMID- 27266242 TI - Acupuncture Treatment for Acute Ankle Injury in the Emergency Department: A Preliminary Case Report. AB - Acupuncture is an ancient medical treatment that is increasingly attracting the interest of the public. It is a complementary therapy that is widely used for management of pain, especially chronic discomfort caused by migraine, low-back pain and osteoarthritis of the knee(1-3). The evidence base for the effectiveness of acupuncture and its clinical applications is controversial, and although its efficacy and safety in the management of acute pain have been demonstrated, the quality of this modality is still questionable. The present study reports a case of acute ankle injury, which was treated with acupuncture. A 33-year-old man presented with acute twisted ankle injury. He had pain with swelling around the ankle, and he was experiencing difficulty in walking. His clinical diagnosis was acute ankle sprain with severe pain. Several drug treatments are used for pain control, but in this case, we used acupuncture. After treatment, his pain diminished significantly with a decrease in VAS pain level from 8 to 4 in 20 minutes. At follow-up after one month, we found no skin infection in this case. PMID- 27266243 TI - Co-Trimoxazole-Induced DRESS Syndrome: A Case Report. AB - Drug Rash with Eosinophilia and Systemic Symptoms (DRESS syndrome) is a severe adverse drug reaction. The drugs, which most commonly induce this condition, are anti-convulsants and sulfonamides. A 15-year-old Thai woman with no known underlying disease was prescribed co-trimoxazole, and two months after initiation, DRESS was diagnosed by RegiSCAR's score. Her clinical symptoms were fever laboratory abnormalities and maculopapular rash on her face, trunk and extremities. She was treated with antipyretics, antihistamines and steroid therapy, and her clinical and laboratory findings were restored to normal by the 10th day of treatment. Early diagnosis, discontinuation of the culprit drug, and management with steroids therapy can reduce the severity of DRESS syndrome. PMID- 27266244 TI - [Plant-Producers Of Recombinant Cytokines (Review)]. AB - Cytokines are a family of signaling polypeptides involved in cell-cell interactions in the process of the immune response, as well as in the regulation of a number of normal physiological functions. Cytokines are used in medicine for the treatment of cancer, immune disorders, viral infections, and other socially significant diseases, but the extent of their use is limited by the high production cost of the active agent. The development of this area of pharmacology is associated with the success of genetic engineering, which allows the production of significant amounts of protein by transgenic organisms. The review discusses the latest advances in the production of various cytokines with the use of genetically modified plants. PMID- 27266245 TI - [Isoformes of Malate Dehydrogenase from Rhodovulum Steppense A-20s Grown Chemotrophically under Aerobic Condtions]. AB - Three malate dehydrogenase isoforms (65-, 60-, and 71-fold purifications) with specific activities of 4.23, 3.88, and 4.56 U/mg protein were obtained in an electrophoretically homogenous state from Rhodovulum steppense bacteria strain A 20s chemotropically grown under aerobic conditions. The physicochemical and kinetic properties of malate dehydrogenase isoforms were determined. The molecular weight and the Michaelis constants were determined; the effect of hydrogen ions on the forward and reverse MDH reaction was studied. The results of the study demonstrated that the enzyme consists of subunits; the molecular weight of subunits was determined by SDS-PAGE. PMID- 27266246 TI - [Study of the Accumulation of Rec A from Bacillus subtilis in the Mitochondria of a Recombinant Strain of the Yeast Yarrowia lipolytica]. AB - No eukaryotic species has a system for homologous DNA recombination of the mitochondrial genome. We report on an integrative genetic systembased on the pQ SRUS construct that allows the expression of the RecA recombinase from Bacillus subtilis and its transportation to mitochondria of Yarrowia lipolytica. The targeting of recombinant RecA to mitochondria is provided by leader sequences (5' UTR and 3-UTR) derived from the SOD2 gene mRNA, which exhibit affinity to the outer mitochondrial membrane and provides cotranslational import of RecA to the inner space of mitochondria. The accumulation of RecA in mitochondria of the Y. lipolytica recombinant strain bearing the pQ-SRUS construct has been shown by immunoblotting of purified mitochondrial preparations. PMID- 27266247 TI - [Expression Of DNA-Encoded Antidote to Organophosphorus Toxins in the Methylotrophic Yeast Pichia Pastoris]. AB - A platform for the cloning and expression of active human butyrylcholinesterase (BuChE) in the yeast Pichia pastoris is first presented. Genetic constructs for BuChE gene expression, separately and in conjunction with a proline-rich peptide called proline-rich attachment domain (PRAD), are based on the vector pPICZalphaA. It is shown that the highest level of production is achieved in the expression of a BuChE gene without PRAD pPICZalphaA. It is found that one can obtain up to 125 mg of active enzyme from 1 L of culture medium at an optimal pH environment (pH 7.6), an optical seed culture density of 3 o.u., and an optimum methanol addition mode of (0.5% methanol in the first day and 0.2% thereafter from the second day). PMID- 27266248 TI - [Engineering of a System for the Production of Mutant Human Alpha-Fetoprotein in the Methylotrophic Yeast Pichia pastoris]. AB - A system for the production of mutant recombinant human alpha-fetoprotein (rhAFPO) lacking the glycosylation site has been engineered in the yeast Pichia pastoris. A strain of the methylotrophic yeast Pichia pastoris GS 115/pPICZ?A/rhAFP0, which produces unglycosylated rhAFPO and secretes it to the culture medium, has been constructed. Optimization and scale-up of the fermentation technology have resulted in an increase in the rhAFP0 yield to 20 mg/L. A scheme of isolation and purification of biologically active rhAFP0 has been developed. The synthesized protein has the antitumor activity, which is analogous to the activity of natural human embryonic alpha-fetoprotein. PMID- 27266249 TI - [Biodegradation of Cellulose-Containing Substrates by Micromycetes Followed by Bioconversion into Biogas]. AB - The ability of micromycetes Trichoderma viride and Aspergillus terreus to decompose the cellulose-containing substrates was studied. Office paper and cardboard, as well as a paper mixture, were found to be the most hydrolyzable. The cellulolytic activity of T. viride was 2-3 times higher than that of A. terreus; the highest values of 0.80 and 0.73 U/mLwere obtained from office paper and the paper mixture, respectively. The micromycete cultivation conditions (composition of culture medium, sucrose cosubstrate addition, seeding method) and the conditions of the fungus biomass treatment for its subsequent bioconversion into biogas by anaerobic microbial communities were optimized. It was shown that pretreatment improves the efficiency of biogas production from lignocellulosic materials under seeding with microbial community of bovine animal manure. After pretreatment of the Jerusalem artichoke phytomass (stems and leaves) and its subsequent bioconversion into biogas by methanogenic community, the biogas yield was increased by 1.5 times. PMID- 27266250 TI - [Enhanced Resistance of Pea Plants to Oxidative: Stress Caused by Paraquat during Colonization by Aerobic Methylobacteria]. AB - The influence of colonization of the pea (Pisum sativum L.) by aerobic methylobacteria of five different species (Methylophilus flavus Ship, Methylobacterium extorquens G10, Methylobacillus arboreus Iva, Methylopila musalis MUSA, Methylopila turkiensis Sidel) on plant resistance to paraquat induced stresses has been studied. The normal conditions of pea colonization by methylobacteria were characterized by a decrease in the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidases) and in the concentrations of endogenous H2O2, proline, and malonic dialdehyde, which is a product of lipid peroxidation and indicator of damage to plant cell membranes, and an increase in the activity of the photosynthetic apparatus (the content of chlorophylls a, b and carotenoids). In the presence of paraquat, the colonized plants had higher activities of antioxidant enzymes, stable photosynthetic indices, and a less intensive accumulation of the products of lipid peroxidation as compared to noncolonized plants. Thus, colonization by methylobacteria considerably increased the adaptive protection of pea plants to the paraquat induced oxidative stress. PMID- 27266251 TI - [Secretion of Phenolic Compounds into Root Exudates of Pea Seedlings upon Inoculation with Rhizobium leguminosarum bv. viceae or Pseudomonas siringae pv. Pisi]. AB - The content of apigenin, naringenin, pisatin, dibutyl-ortho-phthalate, and N phenyl-2-naphthyl-amine were assayed in root exudates of pea (Pisum sativum L.) seedlings one day after their inoculation with Rhizobium leguminosarum, bv. viceae or Pseudomonas siringae pv. pisi, which represent, respectively, mutualistic and antagonistic strategies of interaction with a host plant. After inoculation with either bacteria, the concentrations of apigenin and pisatin in the root exudates were equal, whereas the concentrations of naringenin and N phenyl-2-naphthylamine were different and those of dibutyl-o-phthalate were unchanged. A certain role is suggested for the phenolic compounds in an accomplishment of symbiotic relations of bacteria with a host plant. PMID- 27266252 TI - [Content of Osmolytes and Flavonoids under Salt Stress in Arabidopsis thaliana Plants Defective in Jasmonate Signaling]. AB - The effects of the salt stress (200 mM NaCl) and exogenous jasmonic acid (JA) on levels of osmolytes and flavonoids in leaves of four-week-old Arabidopsis thaliana L. plants of the wild-type (WT) Columbia-0 (Col-0) and the mutant jin1 (jasmonate insensitive 1) with impaired jasmonate signaling were studied. The increase in proline content caused by the salt stress was higher in the Col-0 plants than in the mutant jin1. This difference was especially marked if the plants had been pretreated with exogenous 0.1 uM JA. The sugar content increased in response to the salt stress in the JA-treated WT plants but decreased in the jin1 mutant. Leaf treatment with JA of the WT plants but not mutant defective in jasmonate signaling also enhanced the levels of anthocyanins and flavonoids absorbed in UV-B range. The presence of JA increased salinity resistance of the Col-0 plants, since the accumulation of lipid peroxidation products and growth inhibition caused by NaCl were less pronounced. Under salt stress, JA almost did not render a positive effect on the jin1 plants. It is concluded that the protein JIN1/MYC2 is involved in control of protective systems under salt stress. PMID- 27266253 TI - [Accumulation of alpha-tocopherol and beta-carotene in Euglena gracilis Cells under Autotrophic and Mixotrophic Culture Conditions]. AB - The aim of the work was to find the mode of cultivation of unicellular flagellate Euglena gracilis, favorable for the simultaneous accumulation of alpha-tocopherol and beta-carotene. Cells were grown either in photoautotrophic or photoheterotrophic conditions in the presence of 100 mM ethanol (variant Et) or 40 mM glutamate (variant Gt), or their combination (variant EtGt). The exogenous substrates significantly stimulated light-dependent growth of E. gracilis. The largest increase of biomass was recorded on the 20th day in the variant EtGt and exceeded the autotrophic control by 7 times. The content of beta-carotene and chlorophyll (Chl) per cell in mixotrophic cultures exceeded the control by 2-3 and 1.6-2 times, respectively. At the same time, alpha-tocopherol accumulation in autotrophic cells was greater than in the cells of mixotrophic cultures by 2-7 times. Total yield of tocopherol per unit volume of culture medium, which depended not only on its intracellular content, but also on the amount of accumulated biomass was highest in EtGt variant. A correlation between the accumulation of the antioxidants and the equilibrium concentration of oxygen in the growth medium, which depended on the intensities of photosynthesis and respiration has been analyzed. PMID- 27266254 TI - [Antibacterial Activity of Alkylated and Acylated Derivatives of Low-Molecular Weight Chitosan]. AB - A number of alkylated (quaternized) and acylated derivatives of low-molecular weight chitosan were obtained. The structure and composition of the compounds were confirmed by the results of IR and PMR spectroscopy, as well as conductometric titration. The effect of the acyl substituent and the degree of substitution of N-(2-hydroxy-3-trimethylammonium) with the propyl fragment appended to amino groups of the C2 atom of polymer chains on antibacterial activity against typical representatives of gram-positive and gram-negative microorganisms (Staphylococcus epidermidis and Escherichia coli) was studied. The highest activity was in the case of N-[(2-hydroxy-3 trimethylammonium)propyl]chitosan chloride with the maximal substitution (98%). The minimal inhibitory concentration of the derivative was 0.48 ug/mL and 3.90 ug/mL for S. epidermis and E. coli, respectively. PMID- 27266255 TI - [Binding of Volatile Organic Compounds to Edible Biopolymers]. AB - Capillary gas chromatography was used to study the influence of the composition and structure of different edible polymers (polysaccharides, vegetable fibers, and animal protein gelatin) on the binding of essential oil components. The retention of volatile organic compounds on biopolymers was shown to depend on their molecule structure and the presence, type, and position of a functional group. The maximum extent of the binding was observed for nonpolar terpene and sesquiterpene hydrocarbons, and the minimum extent was observed for alcohols. The components of essential oils were adsorbed due mostly to hydrophobic interactions. It was shown that the composition and structure of a compound, its physico-chemical state, and the presence of functional groups influence the binding. Gum arabic and guar gum were found to bind nonpolar compounds to a maximum and minimum extent, respectively. It was demonstrated the minimum adsorption ability of locust bean gum with respect to all studied compounds. PMID- 27266256 TI - [Effect Of Polyelectrolytes on Catalytic Activity of Alcohol Dehydrogenase]. AB - Fluorescent and optical spectroscopy were used to study the interaction of alcohol dehydrogenase (ADH) with negatively charged polystyrene sulfonate (PSS) and dextran sulfate (DS), as well as positively charged poly(diallyldimethylammonium) (PDADMA). As found, DS and PDADMA did not affect the structural and catalytic enzyme properties. In contrast, PSS slightly decreased the protein self-fluorescence over 1 h of incubation, which is associated with partial destruction of its quaternary (globular) structure. Investigation of the ADH activity with and without PSS showed its dependency on the incubation time and the PSS presence. Sodium chloride (2.0 M and 0.2 M) or ammonium sulfate (0.1 M) added to the reaction mixture did not completely protect the enzyme quaternary structure from the PSS action. However ammonium sulfate or 0.2 M sodium chloride stabilized the enzyme and partially inhibited the negative PSS effect. PMID- 27266257 TI - Heat-Wave Effects on Oxygen, Nutrients, and Phytoplankton Can Alter Global Warming Potential of Gases Emitted from a Small Shallow Lake. AB - Increasing air temperatures may result in stronger lake stratification, potentially altering nutrient and biogenic gas cycling. We assessed the impact of climate forcing by comparing the influence of stratification on oxygen, nutrients, and global-warming potential (GWP) of greenhouse gases (the sum of CH4, CO2, and N2O in CO2 equivalents) emitted from a shallow productive lake during an average versus a heat-wave year. Strong stratification during the heat wave was accompanied by an algal bloom and chemically enhanced carbon uptake. Solar energy trapped at the surface created a colder, isolated hypolimnion, resulting in lower ebullition and overall lower GWP during the hotter-than average year. Furthermore, the dominant CH4 emission pathway shifted from ebullition to diffusion, with CH4 being produced at surprisingly high rates from sediments (1.2-4.1 mmol m(-2) d(-1)). Accumulated gases trapped in the hypolimnion during the heat wave resulted in a peak efflux to the atmosphere during fall overturn when 70% of total emissions were released, with littoral zones acting as a hot spot. The impact of climate warming on the GWP of shallow lakes is a more complex interplay of phytoplankton dynamics, emission pathways, thermal structure, and chemical conditions, as well as seasonal and spatial variability, than previously reported. PMID- 27266258 TI - Ti(N5)4 as a Potential Nitrogen-Rich Stable High-Energy Density Material. AB - We have studied molecular structures and kinetic stabilities of M(N5)3 (M = Sc, Y) and M(N5)4 (M = Ti, Zr, Hf) complexes theoretically. All of these compounds are found to be stable with more than a 13 kcal/mol of kinetic barrier. In particular, Ti(N5)4 showed the largest dissociation energy of 173.0 kcal/mol and thermodynamic stability. This complex had a high nitrogen content (85% by weight), and a significantly high nitrogen to metal ratio (20:1) among the neutral M(N5)n species studied here and in the literature. Ti(N5)4 is thus forecasted to be a good candidate for a nitrogen-rich high-energy density material (HEDM). We reveal in further detail using ab initio molecular dynamics simulations that the dissociation pathways of M(N5)n involve the rearrangements of the bonding configurations before dissociation. PMID- 27266259 TI - N,N,O and N,O,N Meridional cis Coordination of Two Guanines to Copper(II) by d(CGCGCG)2. AB - Many research groups study the generation of supramolecular n-dimensional arrays by combining metals with DNA building blocks. Most of the time, the natural nucleobases are modified to obtain higher-affinity metal binding sites. Using unmodified nucleobases avoids a potentially difficult synthesis; however, they have the possible disadvantage of a less defined and/or weaker coordination mode of the metal. Structural studies on the behavior of copper(II) as a linking metal and guanine as the natural ligand for metals in unmodified DNA are reported. Previously, the ability of mono- and dinuclear metal complexes to induce Z-DNA has been explored [Medina-Molner, A.; Spingler, B. Chem. Commun. 2012, 48, 1961; Medina-Molner, A.; Rohner, M.; Pandiarajan, D.; Spingler, B. Dalton Trans. 2015, 44, 3664]. Herein, X-ray crystallographic studies of the structures resulting from the combination of copper(II) ions with DNA hexamers of the general sequence d(CG)3 are presented. Three different packing motifs were observed in three crystal structures with resolutions ranging from 2.15 to 1.45 A. The motifs are dependent upon other cations being present and/or the crystallization conditions. The first examples of intramolecular O6,N7-chelates of a neutral purine nucleobase to copper(II) were obtained as well as the first meridional N,N,O and N,O,N coordination modes of two guanines to copper(II). The fascinating coordination chemistry of copper(II) complexes generated by the Z-DNA oligonucleotides and the differences to simple nucleobases complexes with copper(II) are discussed in detail. PMID- 27266260 TI - Bivalent Inhibitors of c-Src Tyrosine Kinase That Bind a Regulatory Domain. AB - We have developed a general methodology to produce bivalent kinase inhibitors for c-Src that interact with the SH2 and ATP binding pockets. Our approach led to a highly selective bivalent inhibitor of c-Src. We demonstrate impressive selectivity for c-Src over homologous kinases. Exploration of the unexpected high level of selectivity yielded insight into the inherent flexibility of homologous kinases. Finally, we demonstrate that our methodology is modular and both the ATP competitive fragment and conjugation chemistry can be swapped. PMID- 27266261 TI - Quantitative and In-Depth Survey of the Isotopic Abundance Distribution Errors in Shotgun Proteomics. AB - Accuracy is an important metric when mass spectrometry (MS) is used in large scale quantitative proteomics research. For MS-based quantification by extracting ion chromatogram (XIC), both the mass and intensity dimensions must be accurate. Although much research has focused on mass accuracy in recent years, less attention has been paid to intensity errors. Here, we investigated signal intensity measurement errors systematically and quantitatively using the natural properties of isotopic distributions. First, we defined a normalized isotopic abundance error model and presented its merits and demerits. Second, a comprehensive survey of the isotopic abundance errors using data sets with increasing sample complexities and concentrations was performed. We examined parameters such as error distribution, relationships between signal intensities within one isotopic cluster, and correlations between different peak errors in isotopic profiles. Our data demonstrated that the high resolution MS platforms might also generate large isotopic intensity measurement errors (approximately 20%). Meanwhile, this error can be reduced to less than 5% using a novel correction algorithm, which is based on the theoretical isotopic abundance distribution. Finally, a nonlinear relationship was observed as the abundance error decreased in isotopic profiles with higher intensity. Our findings are expected to provide insight into isotopic abundance recalibration in quantitative proteomics. PMID- 27266262 TI - Left ventricular long axis function assessed during cine-cardiovascular magnetic resonance is an independent predictor of adverse cardiac events. AB - BACKGROUND: Left ventricular pump function requires a complex interplay involving myocardial fibers orientated in the longitudinal, oblique and circumferential directions. Long axis dysfunction appears to be an early marker for a number of pathological states. We hypothesized that mitral annular plane systolic excursion (MAPSE) measured during cine-cardiovascular magnetic resonance (CMR) reflects changes in long axis function and may be an early marker for adverse cardiovascular outcomes. The aims of this study were therefore: 1) To assess the feasibility and reproducibility of MAPSE measurements during routine cine-CMR; and 2) To assess whether MAPSE, as a surrogate for long axis function, is a predictor of major adverse cardiovascular events (MACE). METHODS: Four hundred consecutive patients undergoing CMR were prospectively enrolled. MAPSE was measured in the 4-chamber cine view. Patients were prospectively followed for major adverse cardiac events (MACE) - death, non-fatal myocardial infarction, hospitalization for heart failure or unstable angina, and late revascularization. Cox proportional hazards regression modeling was used to identify factors independently associated with MACE. Net reclassification improvement (NRI) was calculated to assess whether addition of MAPSE resulted in improved risk reclassification of MACE. RESULTS: Seventy-two MACE occurred during a median follow-up of 14.5 months. By Kaplan-Meier analysis, patients with lateral MAPSE <1.11 cm (median) experienced significantly higher incidence of MACE than patients with a MAPSE >=1.11 cm (p = 0.027). After adjustment for established clinical risk factors which were univariate predictors (age, diabetes, hypertension, NYHA class, LV mass), lateral MAPSE remained a significant independent predictor of MACE (HR = 4.384 per cm decrease or 1.344 per 2 mm decrease; p = 0.020). Incorporation of lateral MAPSE into this risk model resulted in a net reclassification improvement (NRI) of 0.18 (p = 0.006). CONCLUSIONS: Reduced long axis function assessed with lateral MAPSE during cine CMR is an independent predictor of MACE. PMID- 27266263 TI - Covert contraceptive use among women attending a reproductive health clinic in a municipality in Ghana. AB - BACKGROUND: Covert contraceptive use (CCU) in sub-Saharan Africa is an indication of women's inability to exercise autonomy in their reproductive choices. The aim of this study was to assess the prevalence and determinants of CCU among a sample of FP clients in a municipality of Ghana. METHODS: We conducted a mixed method study among women attending a public reproductive health clinic in Sunyani, a city of over 250,000 inhabitants in Ghana. An initial survey inquired into sociodemographic characteristics, use of family planning (FP) methods and partner awareness of contraceptive use. The predictors of CCU were explored using logistic regressions. We used the findings to develop a guide which we applied in depth interviews and focus group discussions with attendants at the same facility. Qualitative data analysis was conducted using a framework approach. RESULTS: We interviewed 300 women, 48 % of whom were aged between 26-33 years. The injectable was the most widely used method (56 %). The prevalence of CCU was 34 %. In multivariate analysis, single women were more likely to practice CCU than married or co-habiting women (Adjusted OR = 12.12, 95 % C.I. 4.73-31.1). Muslim and traditionalist women were similarly more likely to practice CCU than non-Muslim, non-traditionalist (Adjusted OR = 4.56, 2.29-9.06). Women who preferred to have their first or next child in 4 or more years from the time of the interview were more likely to be in CCU than women who intended to have children within 4 years of the interview (2.57; 1.37-4.83). Single women saw in covert use a statement of their social autonomy. To succeed in CCU, women wished that clinic attendance cards would not be given to them to keep at home. Though many participants saw in CCU a source of anxiety, they expected health workers to consider it and uphold confidentiality in the provision of services. CONCLUSIONS: Covert contraceptive use was high in this municipality and being single was the strongest predictor of the practice. Providers of FP services should reflect on how to adequately address the challenges faced by women who practice CCU. PMID- 27266264 TI - Intraprocedural left ventricular free wall rupture diagnosed by left ventriculogram in a patient with infero-posterior myocardial infarction and severe aortic stenosis. AB - BACKGROUND: Left ventricular wall rupture remains a major lethal complication of acute myocardial infarction and hypertension is a well-known predisposing factor of cardiac rupture after myocardial infarction. CASE PRESENTATION: An 87-year-old man was admitted to our hospital, diagnosed as acute myocardial infarction (AMI). The echocardiogram showed 0.67-cm(2) aortic valve, consistent with severe aortic stenosis (AS). A coronary angiography showed a chronic occlusion of the proximal left circumflex artery and a 99 % stenosis and thrombus in the mid right coronary artery. During percutaneous angioplasty of the latter, transient hypotension and bradycardia developed at the time of balloon inflation, and low doses of noradrenaline and etilefrine were intravenously administered as needed. The patient suddenly lost consciousness and developed electro-mechanical dissociation. Cardio-pulmonary resuscitation followed by insertion of an intra aortic balloon pump (IABP) and percutaneous cardiopulmonary support were initiated. The echocardiogram revealed moderate pericardial effusion, though the site of free wall rupture was not distinctly visible. A left ventriculogram clearly showed an infero-posterior apical wall rupture. Surgical treatment was withheld because of the interim development of brain death. CONCLUSIONS: In this patient, who presented with severe AS, the administration of catecholamine to stabilize the blood pressure probably increased the intraventricular pressures considerably despite apparently normal measurements of the central aortic pressure. IABP, temporary pacemaker, or both are recommended instead of intravenous catecholamines for patients with AMI complicated with significant AS to stabilize hemodynamic function during angioplasty. PMID- 27266265 TI - Thrombotic microangiopathy as first manifestation of acute human immunodeficiency virus infection: a case report and review of the literature. AB - BACKGROUND: We present the case of a patient with acute human immunodeficiency virus infection and a thrombotic microangiopathy as the first clinical manifestation, a presentation that has not, to the best of our knowledge, been previously reported. CASE PRESENTATION: A 35-year-old Bolivian man presented with epistaxis and thrombocytopenia. We found microangiopathic anemia, lymphopenia, elevated lactate dehydrogenase, progressive acute renal failure, negative direct antiglobulin test, and normal activity of ADAMTS13. An human immunodeficiency virus ELISA test was negative, with an human immunodeficiency virus viral load of 10,000,000 RNA copies/mL. Antiretroviral therapy and three sessions of therapeutic plasma exchange were able to control thrombotic microangiopathy. CONCLUSIONS: Hematologic manifestations of human immunodeficiency virus infection are frequent. However, the debut of acute human immunodeficiency virus infection with thrombotic microangiopathy is a rare event. A high index of suspicion and early treatment is required. PMID- 27266266 TI - 'Candidatus Phytoplasma hispanicum', a novel taxon associated with Mexican periwinkle virescence disease of Catharanthus roseus. AB - Mexican periwinkle virescence (MPV) phytoplasma was originally discovered in diseased plants of Madagascar periwinkle (Catharanthus roseus) in Yucatan, Mexico. On the basis of results from RFLP analysis of PCR-amplified 16S rRNA gene sequences, strain MPV was previously classified as the first known member of phytoplasma group 16SrXIII, and a new subgroup (16SrXIII-A) was established to accommodate MPV phytoplasma. Phylogenetic analysis of 16S rRNA gene sequences indicated that strain MPV represents a lineage distinct from previously described 'CandidatusPhytoplasma' species. Nucleotide sequence alignments revealed that strain MPV shared less than 97.5 % 16S rRNA gene sequence similarity with all previously described 'Ca.Phytoplasma' species. Based on unique properties of the DNA, we propose recognition of Mexican periwinkle virescence phytoplasma strain MPV as representative of a novel taxon, 'CandidatusPhytoplasma hispanicum'. PMID- 27266267 TI - Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations. AB - From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy. PMID- 27266268 TI - Effective Enhancement of Hypoglycemic Effect of Insulin by Liver-Targeted Nanoparticles Containing Cholic Acid-Modified Chitosan Derivative. AB - Liver is responsible for the balance of blood glucose level. In this study, cholic acid and N-(2-hydroxy)-propyl-3-trimethylammonium chloride modified chitosan (HTCC-CA) was used as a liver-targeted vehicle for insulin delivery. A novel approach was developed to effectively load insulin by mixing insulin and HTCC-CA in 50% ethanol and water mixed solvent at pH 2 and then dialysis against pH 7.4 phosphate buffer subsequently against water. The insulin-loaded HTCC-CA nanoparticles have an average diameter of 86 nm and insulin loading efficiency of 98.7%. Due to random distribution of the hydrophobic cholic acid groups in HTCC CA, some of the cholic acid groups located on the nanoparticle surface. Compared with free insulin, the nanoparticles increased in vitro cellular uptake of insulin to 466%, and the nanoparticles accumulated in liver for more time after subcutaneous injection into mice. The therapy for diabetic rats displayed that the nanoparticles increased the pharmacological bioavailability of insulin to 475% relative to free insulin, and the nanoparticles could maintain the hypoglycemic effect for more than 24 h. This study demonstrates that the nanoparticles with cholic acid groups on their surface possess liver-targeted property and biocompatible insulin-loaded HTCC-CA nanoparticles can effectively enhance the hypoglycemic effect of insulin. PMID- 27266269 TI - Design of trials for interrupting the transmission of endemic pathogens. AB - BACKGROUND: Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up. METHODS: A generic model of disease transmission was used to simulate infections in stepped wedge cluster randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs for providing generalizable causal inferences about the impact of such interventions, including measurements of the contamination effects. The simulations were applied to the geography of Rusinga Island, Lake Victoria, Kenya, the site of the SolarMal trial on the use of odor baited mosquito traps to eliminate Plasmodium falciparum malaria. These were used to compare variants in the proposed SWCRT designs for the SolarMal trial. RESULTS: Measures of contamination effects were found that could be assessed in the simulated trials. Inspired by analyses of trials of insecticide-treated nets against malaria when applied to the geography of the SolarMal trial, these measures were found to be robust to different variants of SWCRT design. Analyses of the likely extent of contamination effects supported the choice of cluster size for the trial. CONCLUSIONS: The SWCRT is an appropriate design for trials that assess the feasibility of local elimination of a pathogen. The effects of incomplete coverage can be estimated by analyzing the extent of contamination between arms in such trials, and the estimates also support inferences about causality. The SolarMal example illustrates how generic transmission models incorporating spatial smoothing can be used to simulate such trials for a power calculation and optimization of cluster size and randomization strategies. The approach is applicable to a range of infectious diseases transmitted via environmental reservoirs or via arthropod vectors. PMID- 27266270 TI - Seasonality in diabetes in Yaounde, Cameroon: a relation with precipitation and temperature. AB - BACKGROUND: Diabetes is a growing health concern in developing countries, with Cameroon population having an estimated 6% affected. Of note, hospital attendees appear to be increasing all over the country, with fluctuating numbers throughout the annual calendar. The aim of the study was to investigate the relationship between diabete hospitalization admission rates and climate variations in Yaounde. METHODS: A retrospectively designed study was conducted in four health facilities of Yaounde (Central Hospital, University teaching hospital, Biyem-Assi and Djoungolo District Hospitals), using medical records from 2000 to 2008. A relationship between diabetes (newly diagnosed diabetes patients or decompensated diabetics) hospitalization admissions and climate variations was determined using the "2000-2008" national meteorological database (precipitation and temperature). RESULTS: The monthly medians of precipitation and temperature were 154mm and 25 degrees C, respectively. The month of October received 239mm of precipitation. The monthly medians of diabetic admissions rates (newly diagnosed or decompensated diabetes patients) were 262 and 72 respectively. October received 366 newly diagnosed diabetics and 99 decompensated diabetics. Interestingly, diabetic hospitalization admissions rates were higher during the rainy (51 %, 1633/3232) than the dry season, though the difference was non-significant. The wettest month (October) reported the highest cases (10 %, 336/3232) corresponding to the month with the highest precipitation level (239mm). Diabetes hospitalization admissions rates varied across health facilities [from 6 % (189/3232) in 2000 to 15 % (474/3232) in 2008]. CONCLUSION: Diabetes is an important epidemiological disease in the city of Yaounde. The variation in the prevalence of diabetes is almost superimposed to that of precipitation; and the prevalence seems increasing during raining seasons in Yaounde. PMID- 27266271 TI - Band Structure of the Rhodobacter sphaeroides Photosynthetic Reaction Center from Low-Temperature Absorption and Hole-Burned Spectra. AB - Persistent/transient spectral hole burning (HB) and computer simulations are used to provide new insight into the excitonic structure and excitation energy transfer of the widely studied bacterial reaction center (bRC) of Rhodobacter (Rb.) sphaeroides. We focus on site energies of its cofactors and electrochromic shifts induced in the chemically oxidized (P(+)) and charge-separated (P(+)QM(-)) states. Theoretical models lead to two alternative interpretations of the H-band. On the basis of our experimental and simulation data, we suggest that the bleach near 813-825 nm in transient HB spectra in the P(+)QM(-) state, often assigned to the upper exciton component of the special pair, is mostly due to different electrochromic shifts of the BL/M cofactors. From the exciton compositions in the charge-neutral (CN) bRC, the weak fourth excitonic band near 780 nm can be denoted PY+, that is, the upper excitonic band of the special pair, which in the CN bRC behaves as a delocalized state over PM and PL pigments that weakly mixes with accessory BChls. Thus, the shoulder in the absorption of Rb. sphaeroides near 813-815 nm does not contain the PY+ exciton band. PMID- 27266272 TI - An unusual case of congenital cytomegalovirus infection-related retinopathy. AB - BACKGROUND: Cytomegalovirus (CMV) is the most common congenital infection, and chorioretinitis is the most common ophthalmic manifestation of congenital CMV infection. We experienced a unique case of CMV retinopathy showing unusual retinal vessels. CASE PRESENTATION: An infant boy weighing 1860 g was born at 36 weeks. He was diagnosed with severe symptomatic congenital CMV infection, which was confirmed by positive CMV-DNA in urine and whole blood, and he was referred to our ophthalmology department on his first day of life. Ophthalmoscopic examination and fluorescein angiography revealed no chorioretinitis but major retinal vascular occlusions and arterio-venous anastomosis associated with CMV detection in the aqueous humor. These findings regressed within a week after treatment with systemic gancyclovir administration. CONCLUSIONS: To our knowledge, there are no reports of these ocular issues associated with congenital CMV infection. These findings may be useful for the early and rapid diagnosis of congenital CMV infection. PMID- 27266273 TI - Varicella-zoster virus susceptibility and primary healthcare consultations in Norway. AB - BACKGROUND: Currently Norway does not recommend universal varicella vaccination for healthy children. This study assessed susceptibility to varicella-zoster virus (VZV) in the Norwegian population for the first time. METHODS: A national convenience sample of residual sera was tested for anti-VZV IgG by ELISA. We estimated age-specific seropositivity to VZV, controlling for sex and geographical distribution. We assessed differences between the proportions using the chi-square test and multivariable logistic regression. Seroprevalence data were compared to the varicella and herpes zoster-associated consultation rates in patients attending primary healthcare. RESULTS: Although 73.2 % (n = 1,540) of all samples were positive for VZV, only 11.2 % of samples collected from 1-year olds were seropositive. There was a sharp increase in the proportion of seropositive in 3- and 5-year-olds (40.2 % and 65.4 %, respectively). By the school entry age of 6 years, 69.8 % of children were seropositive. The age specific annual consultation rate for varicella in primary healthcare peaked in 1 year-olds, with 2,627 cases per 100,000 population. The profile of varicella related consultations in primary healthcare mirrored the VZV seropositivity profile. The herpes zoster-related consultations in primary healthcare peaked in people over 70 years of age (702 cases per 100,000 population). CONCLUSIONS: VZV seroprevalence in Norway was somewhat lower than in some other European countries. The age-specific varicella-related consultation rates in primary healthcare mirrored the age profile of VZV seroprevalence. PMID- 27266275 TI - Minimally invasive versus open surgery for acute Achilles tendon rupture: a systematic review of overlapping meta-analyses. AB - BACKGROUND: A number of meta-analyses have been carried out to evaluate the effects of minimally invasive surgery (MIS) versus open surgery (OS) for acute Achilles tendon rupture. However, discordant findings were seen in these meta analyses. The present study, performing a systematic review of overlapping meta analyses regarding MIS versus OS of acute Achilles tendon rupture, aimed to assist decision-makers interpret and choose among conflicting meta-analyses, as well as to offer treatment recommendations based on current best evidence. METHODS: The literature search was performed to identify systematic reviews comparing MIS with OS for Achilles tendon rupture. Meta-analyses only comprising randomized controlled trials (RCTs) were included. Two authors individually evaluated the quality of meta-analysis and extracted data. The Jadad decision algorithm was conducted to ascertain which meta-analysis offered the best evidence. RESULTS: A total of four meta-analyses was included. All these meta analyses comprised RCTs or quasi-RCTs and were determined as Level-II evidence. The scores of the Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 7 to 10 (median 9.5). The Jadad algorithm indicated that the best meta-analysis should be chosen according to the search strategies and application of selection. A high-quality meta-analysis with more RCTs was chosen, which suggested that there was no statistically significant difference between MIS and OS regarding rerupture rate, tissue adhesion, sural nerve injury, deep infection, and deep vein thrombosis. However, MIS could decrease superficial infection rate, and had a better patient satisfaction for good to excellent outcomes in comparison to OS. CONCLUSIONS: Based on the best available evidence, MIS may be superior to OS for treating acute Achilles tendon rupture. However, due to some limitations, this should be cautiously interpreted, and further high-quality studies are needed. PMID- 27266274 TI - Connexin 43 and CaV1.2 Ion Channel Trafficking in Healthy and Diseased Myocardium. PMID- 27266276 TI - Hypothetical biomolecular probe based on a genetic switch with tunable symmetry and stability. AB - BACKGROUND: Genetic switches are ubiquitous in nature, frequently associated with the control of cellular functions and developmental programs. In the realm of synthetic biology, it is of great interest to engineer genetic circuits that can change their mode of operation from monostable to bistable, or even to multistable, based on the experimental fine-tuning of readily accessible parameters. In order to successfully design robust, bistable synthetic circuits to be used as biomolecular probes, or understand modes of operation of such naturally occurring circuits, we must identify parameters that are key in determining their characteristics. RESULTS: Here, we analyze the bistability properties of a general, asymmetric genetic toggle switch based on a chemical reaction kinetic description. By making appropriate approximations, we are able to reduce the system to two coupled differential equations. Their deterministic stability analysis and stochastic numerical simulations are in excellent agreement. Drawing upon this general framework, we develop a model of an experimentally realized asymmetric bistable genetic switch based on the LacI and TetR repressors. By varying the concentrations of two synthetic inducers, doxycycline and isopropyl beta-D-1-thiogalactopyranoside, we predict that it will be possible to repeatedly fine-tune the mode of operation of this genetic switch from monostable to bistable, as well as the switching rates over many orders of magnitude, in an experimental setting. Furthermore, we find that the shape and size of the bistability region is closely connected with plasmid copy number. CONCLUSIONS: Based on our numerical calculations of the LacI-TetR asymmetric bistable switch phase diagram, we propose a generic work-flow for developing and applying biomolecular probes: Their initial state of operation should be specified by controlling inducer concentrations, and dilution due to cellular division would turn the probes into memory devices in which information could be preserved over multiple generations. Additionally, insights from our analysis of the LacI-TetR system suggest that this particular system is readily available to be employed in this kind of probe. PMID- 27266278 TI - Synthesis of Aryl Ketoamides via Aryne Insertion into Imides. AB - An insertion of arenes into both imides and anhydrides via reactive aryne intermediates is presented. The reaction is performed under exceptionally mild conditions, and the corresponding ketoamide products are amenable to derivatization to deliver a variety of synthetically useful motifs such as quinolones, indoles, and ketoanilines. PMID- 27266277 TI - Low-level prenatal lead exposure and infant sensory function. AB - BACKGROUND: Lead is a pervasive neurotoxicant that has been associated with poorer cognitive, behavioral, and motor outcomes in children. The effects of lead on sensory function have not been well characterized. The aim of this study was to assess the effects of prenatal lead exposure on infant sensory function, as measured by auditory brainstem response (ABR) and grating visual acuity (VA). METHODS: Lead was measured in maternal blood in mid- and late-pregnancy (mean gestational age = 15.5 and 39.0 weeks, respectively) and umbilical cord blood in a cohort of full-term infants in rural northeastern China. ABR latencies (peaks I, III, V) were measured in newborns during unsedated sleep (n = 315). The ABR central-to-peripheral (C-P) ratio was calculated as the ratio between the III-V and I-III interpeak intervals. VA was measured in 6-week-olds using Teller Acuity Cards (n = 1019) and assigned as the narrowest grid the infant fixated on. Multivariate linear regression was used to evaluate relationships between tertiles of mid-pregnancy, late-pregnancy, or cord lead and newborn ABR or 6-week VA. RESULTS: Higher late-pregnancy lead levels were associated with higher ABR C P ratios and lower VA. In covariate-adjusted analyses, mean C-P ratios were 4.6 and 3.2 % higher in infants whose mothers had lead > 3.8 MUg/dL and lead = 2-3.8 MUg/dL, respectively, than for infants whose mothers had lead < 2 MUg/dL (p-trend =0.002). In adjusted analyses for VA, mean scores were 8.5 and 7.2 % lower for maternal lead > 3.8 MUg/dL and lead = 2-3.8 MUg/dL, respectively, compared to lead < 2 MUg/dL (p-trend =0.009). CONCLUSION: Auditory and visual systems maturation appears delayed in infants with higher prenatal lead exposure during late-pregnancy, even at relatively low levels. Both systems start myelinating in late gestation and mature rapidly in infancy. Higher ABR C-P ratio and lower grating VA scores suggest effects of low-level lead exposure on sensory system myelination. PMID- 27266279 TI - Approach of pulmonologists in Turkey to noninvasive mechanical ventilation use at home for chronic respiratory failure. AB - INTRODUCTION: To define approach of pulmonologists in Turkey to noninvasive mechanical ventilation (NIV) use for chronic respiratory failure (CRF), the most currently applied technique for home mechanical ventilation. PATIENTS AND METHODS: A 38-question survey, developed and tested by the authors, was distributed throughout Turkey to 2205 pulmonologists by e-mail. RESULT: Twenty seven percent of the pulmonologists responded (n=596). Domiciliary NIV was reported to be prescribed by 340 physicians [57.1% of all responders and 81% of pulmonologists practicing NIV at clinical practice (n= 420)]. NIV prescription was associated with physician's title, type of hospital, duration of medical license, total number of patients treated with NIV during residency and current number of patients treated with NIV per week (p< 0.05). Main estimated indications were listed as chronic obstructive pulmonary disease (median, 25-75 percentile of the prescriptions: 75%, 60-85), obesity hypoventilation syndrome (10%, 2-15), overlap syndrome (10%, 0-20) and restrictive lung disease (5%, 2 10). For utilization of NIV at home, Bilevel positive airway pressure-spontaneous mode (40%, 0-80) and oronasal mask (90%, 60-100) were stated as the most frequently recommended mode and interface, respectively. Pressure settings were most often titrated based on arterial blood gas findings (79.2%). Humidifier was stated not to be prescribed by approximately half of the physicians recommending domicilliary NIV, and the main reason for this (59.2%) was being un-refundable by social security foundation. CONCLUSION: There is a wide variation in Turkey for prescription of NIV, which is supposed to improve clinical course of patients with CRF. Further studies are required to determine the possible causes of these differences, frequency of use and patient outcomes in this setting. PMID- 27266280 TI - Evaluation of pulmonary microsporidiosis in iatrogenically immunosuppressed patients. AB - INTRODUCTION: Microsporidia spp. are ubiquitous and infect a wide variety of intervertebrates and vertebrates, including humans. Pulmonary microsporidiosis, characterized by nonspecific symptoms like fever, cough and dyspnea, is often overlooked in the differential diagnosis of pulmonary infections in immunsupressed patients. In this study, we aimed to determine the prevalence of pulmonary microsporidiosis in iatrogenically immunosuppressed patients and to evaluate the patient characteristics. MATERIALS AND METHODS: Bronchoalveolar lavage (BAL) specimens from 63 iatrogenically immunosuppressed patients and 28 controls were examined with PCR. By using PMP1 and PMP2 common primers specifically designed for Enterocytozoon bieneusi, Encephalitozoon intestinalis, Encephalitozoon cuniculi and Encephalitozoon hellem small-subunit ribosomal DNA (SSU-rDNA) regions at 250-279 bp were amplified. In addition, PCR positive BAL specimens were examined with modified trichrome staining method for Microsporidia spores. RESULT: Out of 63 immunosuppressed patients, nine (14.2%) had Microsporidia spp., but none of the control patients had Microsporidia spp. on PCR. This difference between two groups was statistically significant (chi2 =4.439; p=0.035). On the other hand there was not a statistically significant relationship between PCR positivity and patient characteristics such as gender and age. Of nine patients with Microsporidia PCR positive, only one had spores of Microsporidia sp. Out of eight patients without spores, one had Mycobacterium tuberculosis, one patient had Klebsiella pneumoniae and five patients had Pneumocystis jirovecii DNA. CONCLUSION: This is the first study to evaluate the pulmonary microsporidiosis in immunosupressed patients in Turkey. The results of the study indicated that Microsporidia spp. should be taken into account in the differential diagnosis of pulmonary infections in immunosupressed patients and it is important to use molecular methods such as PCR in the laboratory diagnosis of the causative agent. PMID- 27266281 TI - [Efficiency of nebulised magnesium sulphate in infective exacerbations of chronic obstructive pulmonary disease]. AB - INTRODUCTION: Conflicting results has been achieved in a small number of clinical studies evaluating the efficiency of magnesium sulphate (MS) in COPD exacerbations. We aimed to investigate the efficiency of nebulised MS in COPD exacerbations. PATIENTS AND METHODS: Twenty patients who met the study criteria were randomized into two groups. All patients were treated with O2, antibiotics and oral corticosteroids. Additionally one group received ipratropium bromide (IB) 500 ug together with MS 151 mg/dose, while the other group received IB together with placebo. The patients were followed-up with forced expiratory volume in 1 second (FEV1) and visual analogue scale dyspnea scores for 48 hours. Peak expiratory flow rates (PEFRs) were measured before and 10, 30, 60 and 120 minutes after each nebule treatment. RESULT: The baseline characteristics of the patients in both groups were similar. The FEV1 values measured at 24 and 48 hours did not show significant changes compared to baseline in both groups. Dyspnea scores in both groups decreased significantly in the first day, and in only MS group in the second day. The % change in the dyspnea score at the end of first day was significantly more in the MS group [-23.8% (13.6)] compared with the placebo group [-9.4% (12.9)] (p= 0.002). The % changes in PEFRs at 10 minutes [4.7 (7.5) and -3.5 (6.0), p= 0.005] and 30 minutes [8.2 (6.7) and 1.3 (5.5), p= 0.03] were significantly greater in the MS group compared with the placebo group on the first day. No side effects developed due to MS. CONCLUSION: Nebulised MS is a cheap, feasible and safe drug that can be added to the standart bronchodilator treatment since it provides additional relief of dyspnea in patients with COPD exacerbations. This needs to be evaluated in future clinical studies including greater number of patients. PMID- 27266282 TI - Tuberculosis screening and efficacy of prophylaxis in contacts of patients with pulmonary tuberculosis. AB - INTRODUCTION: To evaluate tuberculosis screening and efficacy of prophylaxis in contacts of patients with pulmonary tuberculosis. PATIENTS AND METHODS: A total of 7453 contacts of 1909 patients with pulmonary tuberculosis treated at four tuberculosis dispensaries located in Istanbul, between 2005 and 2009 were included in this retrospective screening-based study. Data on demographics, smear positivity, PPD positivity, rate and onset of secondary tuberculosis and prophylaxis were recorded in contacts. RESULT: Overall 184 (2.5%) secondary cases of tuberculosis were identified within a mean 2.9 (1-5) years of follow-up. The rate for secondary tuberculosis was 3.1% (163/5335) in smear positive and 1.0% (20/2118) in smear negative contacts. With and without prophylaxis rates for secondary tuberculosis after 6 months of index case was identified in 0.7% (6/912) and 2.0% (9/455) of contacts aged 0-15 years, in 0.9% (3/339) and 2.8% (51/1826) of contacts aged 16-35 years and in 0% (0/215) and 0.9% (14/1507) of contacts aged >= 36 years, respectively. CONCLUSION: In conclusion, our findings indicate high risk of being infected and diseased in smear positive contacts along with efficacy of prophylactic therapy among contacts not only in the childhood but also in adults, particularly in contacts aged 16-35 years. PMID- 27266283 TI - The sensitivity and specifity of DR-70 immunoassay as a tumor marker for non small cell lung cancer. AB - INTRODUCTION: Lung cancer is the most important causes of the cancer related mortality. Patients with lung cancer are usually diagnosed at advanced or locally advanced stage, for this reason early diagnosis of lung cancer is very important. For early detection of lung cancer some methods are emphasized such as low-dose computed tomography or tumor biomarkers. In this study we aimed to evaluate DR-70 sensitivity and specificity as a tumor marker in detection of non-small cell lung cancers. PATIENTS AND METHODS: Between May 2013 and April 2014, the serum samples from 88 non lung cancer patients, 86 patients with chronic obstructive pulmonary disesase were obtained. Blood samples from each participant were analyzed for DR 70 level. RESULT: Totally 174 patients were enrolled to the study (152 male, 22 female). Histopathologically 47(53.4%) patients were diagnosed with squamous cell lung cancer, 34 (38.6%) with adenocarcinoma, and 7 (8%) with non-small cell lung cancer. The mean serum DR-70 levels in lung cancer patients (2.43 +/- 1.82 ug/mL) was significantly higher compared to the 86 non-cancerous subjects (1.15 +/- 0.70 ug/mL) (p< 0.01). DR-70 exhibited clinical sensitivity and specificity of 54.5 and 83.7%, respectively, at an optimal cut off at 1.98 ug/mL. It could be said that the risk of the presence of the disease is 6.171 times higher in the cases where DR-70 level is 1.98 ug/mL and higher. CONCLUSION: DR-70, a marker used to measure fibrin degradation products, generated by all major cancers, may helps to find high risk lung cancer patients. PMID- 27266284 TI - The awareness of chest physicians about nutritional assessment in chronic obstructive pulmonary disease. AB - INTRODUCTION: The number of studies that target nonpharmacologic treatments for chronic obstructive pulmonary disease (COPD) are increasing because no existing pharmacologic treatment modality for COPD leads to significant improvement in lung function.Positive effects can be observed in patients with COPD using nutritional support alone or as an adjunct to exercise. In this study, we aimed to evaluate the awareness of chest physicians about the nutritional state of patients with COPD. MATERIALS AND METHODS: A questionnaire consisting of 15 multiple choice questions was conducted to 121 chest physicians. The questions were formed to evaluate the awareness of chest physicians on the patients' nutritional state and the importance of nutrition in COPD follow-up. RESULT: In total, of the 121 physicians, only 3 (2.5%) reported undertaking routine assessment for nutritional state of patients with COPD. The rates of physicians who routinely questioned patients about weight loss and loss of appetite were 56.2% (n= 68) and 51.2% (n= 62), respectively. Forty-five (37.2%) physicians said that they usually started nutritional support if they detected weight loss in patients with COPD. CONCLUSION: Although there is limited data on the benefits of nutritional supplementation for patients with COPD, some studies have suggested advantages of nutritional support against the progress of COPD. Our study showed that routine screening for malnutrition in patients with COPD is rare among chest physicians and this did not differ according to the hospitals in which they worked or from where they took their residency training. There is a need for further studies emphasizing the importance of nutritional state in the progress of COPD. PMID- 27266285 TI - [Epigenetic and current treatment approaches in chronic obstructive pulmonary disease]. AB - Epigenetics mechanisms such as DNA methylation, histone acetylation and non coding RNAs may play are a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Researchs with regard epigenetic in COPD can shed light on pathogenes and may be relevant in the development of novel targeted therapies. The aim of this article is to review epigenetic mechanisms new treatments approaches in COPD. PMID- 27266286 TI - A cytopathological approach to diagnosing intrathoracic lymphadenopathy using aspirates obtained by the transbronchial needle aspiration method. AB - Transbronchial needle aspiration (TBNA) is an effective, safe and cost-effective technique that allows for sampling of the mediastinal lymph node and peribronchial lesions. It is used in bronchogenic carcinoma staging, peribronchial and submucosal lesions, diagnosis of sarcoidosis and tuberculosis, differentiating submucosal invasion, and in diagnosing mediastinal masses. From our experience at the University of Abant Izzet Baysal and from a review of the literature, we discuss the adequacy and the differential diagnosis of aspiration material obtained by TBNA and cytopathological-histopathological evaluation in intrathoracic lymphadenopathies to increase the success rate of the TBNA method. PMID- 27266287 TI - [Drug carrier nanosystems in malignant pleural mesothelioma]. AB - Malignant pleural mesothelioma (MPM), the incidence increased with each passing day, is an important lethal disease due to the limited survive with available treatment methods and with the lack of a standard treatment. Response and survive rates of cytotoxic agents which is used in MPM treatment are not good enough. Therefore, treatment studies of MPM seem to quite important and urgent. In cancer therapy, convensional chemotherapeutic agent applications, due to the lack of selectivity, lead to systemic toxicity. Besides the limited solubility of the agent used, the distribution between the cells is weak. It is very difficult to the pass through cellular barriers, particularly, drug resistance may develop to the treatment. All of these reasons lead to failure in the treatment process. Because of the fact that cytotoxic drugs either kill the rapidly growing and dividing cells or make them disfunctional by showing toxic effect on them, to avoid the side effects and to make an inherent effect for cytotoxic drug of active ingredient given for treatment on tumor, different studies have been under investigation. At the present time, nanocarriers as one of these solutions seem to have an important place. Nanocarriers are promising for the development of therapeutic effectiveness and safety. It seems that use of the nanocarrier in the treatment of mesothelioma has a potential, as effective alternative a method, with improve of the drug efficacy and reduce of toxicity in normal tissues. PMID- 27266288 TI - beta-HCG secretion by a non-small cell lung cancer: a case report. AB - Paraneoplastic secretion of beta human chorionic gonadotropin (beta-HCG) in non small cell lung cancer (NSCLC) has been rarely reported. A 43-year old male patient was admitted with dyspnea and chest pain. Thorax computed tomography (CT) revealed bilateral multiple masses and pleural effusion at right hemithorax. Positron emission tomography (PET)-CT showed pathologic 18 FDG uptake at mass lesions and mediastinal lymph nodes. The serum beta-HCG level was elevated. A bronchoscopy was performed and endobronchial lesion was observed. Since a definitive diagnosis was not achieved by pathologic examination of biopsy specimen, bronchoscopy was repeated and a sample was taken by cryobiopsy. The pathologic examination revealed non-small cell lung cancer.In conclusion, the case was presented because of extremely rare occurence of NSCLC secreting beta HCG. PMID- 27266289 TI - An uncommon cause of multiple pulmonary nodules; hereditary hemorrhagic telangiectasia. AB - Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome (ROWS) is a very rare hereditary disease. The diagnosis is based on the clinical findings such as recurrent epistaxis, telangiectases, visceral arteriovenous malformations (AVMs) and family history. AVMs are found in the liver, lung or brain and could mimick the masses of these organs. Radiologic evaluation plays a critical role during diagnostic and therapeutic management of ROWS. Hence, radiologists should be aware of the diagnosis of HHT in the patients with AVMs, history of epistaxis and family history. We report a patient with multiple pulmonary AVMs secondary to HHT who has referred to our interventional radiology department for computed tomography guided transthorasic lung biopsy procedure with suspicious of malignancy. PMID- 27266290 TI - Tracheal diverticulum: an unusual cause of chronic cough and recurrent respiratory infections. AB - Tracheal diverticulum (TD) defined as a typical benign out-pouching of the tracheal wall due to structural weakness, congenital or acquired in origin, resulting in paratracheal air cysts. It is rarely diagnosed in clinical practice with only limited reports in the literature. Most cases found incidentally in the postmortem examination and located on the right side. Uncomplicated TDs are usually asymptomatic and when symptoms have occurred, they usually present with non-specific symptoms like pharyngeal discomfort, cough, dyspnea, and recurrent respiratory infection due to either the compression of adjacent organs or secondary bacterial infection. Imaging techniques like thoraco-cervical multi slice spiral computed tomography (CT) and fiber-optic bronchoscopy are important diagnostic tools for this entity. Asymptomatic TDs usually require no treatment and managed conservatively while surgical excision is indicated in cases of compression of adjacent organs and recurrent infections. Here we report a case of tracheal diverticulum on the left side, which was diagnosed as part of a work-up for chronic cough and recurrent chest infection in a 40 year old female who was already on bronchodilator without any relief. Diagnosis of TD was based on findings of computed tomography, revealing small bud like projection on left para tracheal region and further confirmed by fiber-optic bronchoscopy while the barium contrast study showed no esophageal communication. She was managed conservatively and referred for surgical excision. PMID- 27266291 TI - Removal of extracorporeal carbon dioxide in chronic obstructive pulmonary disease patients. AB - The use of invasive mechanical ventilation (IMV) procedures in chronic obstructive pulmonary disease (COPD) patients suffering from episodes of acute exacerbation are associated with high rates of mortality. In this case study, we describe the use of a new device for extracorporeal carbon dioxide removal (ECCO2R) that can provide partial respiratory support for patients where noninvasive ventilation (NIV) proved insufficient. The case described in this manuscript represents the first clinical feasibility study for the Hemolung device, and was also the first use and application of the device at our department. PMID- 27266292 TI - The radiological appearance of a giant intrathoracic fibrolipoma. PMID- 27266293 TI - [The newly defined entity: combined pulmonary fibrosis and emphysema syndrome]. PMID- 27266294 TI - Waterpipe tobacco smoking. PMID- 27266295 TI - GPs in Northern Ireland face "full blown crisis," BMA warns. PMID- 27266296 TI - A barrier to metal movement: Synchrotron study of iron plaque on roots of wetland plants. PMID- 27266297 TI - Structural and metabolic responses of microbial community to sewage-borne chlorpyrifos in constructed wetlands. AB - Long-term use of chlorpyrifos poses a potential threat to the environment that cannot be ignored, yet little is known about the succession of substrate microbial communities in constructed wetlands (CWs) under chlorpyrifos stress. Six pilot-scale CW systems receiving artificial wastewater containing 1mg/L chlorpyrifos were established to investigate the effects of chlorpyrifos and wetland vegetation on the microbial metabolism pattern of carbon sources and community structure, using BIOLOG and denaturing gradient gel electrophoresis (DGGE) approaches. Based on our samples, BIOLOG showed that Shannon diversity (H') and richness (S) values distinctly increased after 30days when chlorpyrifos was added. At the same time, differences between the vegetated and the non vegetated systems disappeared. DGGE profiles indicated that H' and S had no significant differences among four different treatments. The effect of chlorpyrifos on the microbial community was mainly reflected at the physiological level. Principal component analysis (PCA) of both BIOLOG and DGGE showed that added chlorpyrifos made a difference on test results. Meanwhile, there was no difference between the vegetation and no-vegetation treatments after addition of chlorpyrifos at the physiological level. Moreover, the vegetation had no significant effect on the microbial community at the genetic level. Comparisons were made between bacteria in this experiment and other known chlorpyrifos degrading bacteria. The potential chlorpyrifos-degrading ability of bacteria in situ may be considerable. PMID- 27266298 TI - An overview of emissions of SO2 and NOx and the long-range transport of oxidized sulfur and nitrogen pollutants in East Asia. AB - The long-range transport of oxidized sulfur (sulfur dioxide (SO2) and sulfate) and oxidized nitrogen (nitrogen oxides (NOx) and nitrate) in East Asia is an area of increasing scientific interest and political concern. This paper reviews various published papers, including ground- and satellite-based observations and numerical simulations. The aim is to assess the status of the anthropogenic emissions of SO2 and NOx and the long-range transport of oxidized S and N pollutants over source and downwind region. China has dominated the emissions of SO2 and NOx in East Asia and urgently needs to strengthen the control of their emissions, especially NOx emissions. Oxidized S and N pollutants emitted from China are transported to Korea and Japan, due to persistent westerly winds, in winter and spring. However, the total contributions of China to S and N pollutants across Korea and Japan were not found to be dominant over longer time scales (e.g., a year). The source-receptor relationships for oxidized S and N pollutants in East Asia varied widely among the different studies. This is because: (1) the nonlinear effects of atmospheric chemistry and deposition processes were not well considered, when calculating the source-receptor relationships; (2) different meteorological and emission data inputs and solution schemes for key physical and chemical processes were used; and (3) different temporal and spatial scales were employed. Therefore, simulations using the same input fields and similar model configurations would be of benefit, to further evaluate the source-receptor relationships of the oxidized S and N pollutants. PMID- 27266299 TI - Uptake of radioiodide by Paenibacillus sp., Pseudomonas sp., Burkholderia sp. and Rhodococcus sp. isolated from a boreal nutrient-poor bog. AB - Radionuclides, like radioiodine ((129)I), may escape deep geological nuclear waste repositories and migrate to the surface ecosystems. In surface ecosystems, microorganisms can affect their movement. Iodide uptake of six bacterial strains belonging to the genera Paenibacillus, Pseudomonas, Burkholderia and Rhodococcus isolated from an acidic boreal nutrient-poor bog was tested. The tests were run in four different growth media at three temperatures. All bacterial strains removed iodide from the solution with the highest efficiency shown by one of the Paenibacillus strains with >99% of iodide removed from the solution in one of the used growth media. Pseudomonas, Rhodococcus and one of the two Paenibacillus strains showed highest iodide uptake in 1% yeast extract with maximum values for the distribution coefficient (Kd) ranging from 90 to 270L/kg DW. The Burkholderia strain showed highest uptake in 1% Tryptone (maximum Kd 170L/kg DW). The Paenibacillus strain V0-1-LW showed exceptionally high uptake in 0.5% peptone +0.25% yeast extract broth (maximum Kd>1,000,000L/kg DW). Addition of 0.1% glucose to the 0.5% peptone +0.25% yeast extract broth reduced iodide uptake at 4 degrees C and 20 degrees C and enhanced iodide uptake at 37 degrees C compared to the uptake without glucose. This indicates that the uptake of glucose and iodide may be competing processes in these bacteria. We estimated that in in situ conditions of the bog, the bacterial uptake of iodide accounts for approximately 0.1%-0.3% of the total sorption of iodide in the surface, subsurface peat, gyttja and clay layers. PMID- 27266300 TI - Development of a field enhanced photocatalytic device for biocide of coliform bacteria. AB - A field enhanced flow reactor using bias assisted photocatalysis was developed for bacterial disinfection in lab-synthesized and natural waters. The reactor provided complete inactivation of contaminated waters with flow rates of 50mL/min. The device consisted of titanium dioxide nanotube arrays, with an externally applied bias of up to 6V. Light intensity, applied voltage, background electrolytes and bacteria concentration were all found to impact the device performance. Complete inactivation of Escherichia coli W3110 (~8*10(3)CFU/mL) occurred in 15sec in the reactor irradiated at 25mW/cm(2) with an applied voltage of 4V in a 100ppm NaCl solution. Real world testing was conducted using source water from Emigration Creek in Salt Lake City, Utah. Disinfection of natural creek water proved more challenging, providing complete bacterial inactivation after 25sec at 6V. A reduction in bactericidal efficacy was attributed to the presence of inorganic and organic species, as well as the increase in robustness of natural bacteria. PMID- 27266301 TI - Characterisation and seasonal variations of particles in the atmosphere of rural, urban and industrial areas: Organic compounds. AB - Atmospheric aerosol samples (PM2.5-0.3, i.e., atmospheric particles ranging from 0.3 to 2.5MUm) were collected during two periods: spring-summer 2008 and autumn winter 2008-2009, using high volume samplers equipped with cascade impactors. Two sites located in the Northern France were compared in this study: a highly industrialised city (Dunkirk) and a rural site (Rubrouck). Physicochemical analysis of particulate matter (PM) was undertaken to propose parameters that could be used to distinguish the various sources and to exhibit seasonal variations but also to provide knowledge of chemical element composition for the interpretation of future toxicological studies. The study showed that PM2.5-0.3 concentration in the atmosphere of the rural area remains stable along the year and was significantly lower than in the urban or industrial ones, for which concentrations increase during winter. High concentrations of polycyclic aromatic hydrocarbons (PAHs), dioxins, furans and dioxin like polychlorinated biphenyls (DL-PCBs), generated by industrial activities, traffic and municipal wastes incineration were detected in the samples. Specific criteria like Carbon Preference Index (CPI) and Combustion PAHs/Total PAHs ratio (CPAHs/TPAHs) were used to identify the possible sources of atmospheric pollution. They revealed that paraffins are mainly emitted by biogenic sources in spring-summer whereas as in the case of PAHs, they have numerous anthropogenic emission sources in autumn winter (mainly from traffic and domestic heating). PMID- 27266302 TI - Temporal and spatial changes of microbial community in an industrial effluent receiving area in Hangzhou Bay. AB - Anthropogenic activities usually contaminate water environments, and have led to the eutrophication of many estuaries and shifts in microbial communities. In this study, the temporal and spatial changes of the microbial community in an industrial effluent receiving area in Hangzhou Bay were investigated by 454 pyrosequencing. The bacterial community showed higher richness and biodiversity than the archaeal community in all sediments. Proteobacteria dominated in the bacterial communities of all the samples; Marine_Group_I and Methanomicrobia were the two dominant archaeal classes in the effluent receiving area. PCoA and AMOVA revealed strong seasonal but minor spatial changes in both bacterial and archaeal communities in the sediments. The seasonal changes of the bacterial community were less significant than those of the archaeal community, which mainly consisted of fluctuations in abundance of a large proportion of longstanding species rather than the appearance and disappearance of major archaeal species. Temperature was found to positively correlate with the dominant bacteria, Betaproteobacteria, and negatively correlate with the dominant archaea, Marine_Group_I; and might be the primary driving force for the seasonal variation of the microbial community. PMID- 27266303 TI - Profiling kidney microRNAs from juvenile grass carp (Ctenopharyngodon idella) after 56days of oral exposure to decabromodiphenyl ethane. AB - Grass carp (Ctenopharyngodon idella) is one of the most important species in China. Decabromodiphenyl ethane (DBDPE) is a brominated flame retardant that has been used widely in industry, and has been observed to accumulate in the tissues of fish from South China. Evidence has shown that DBDPE is toxic to aquatic animals, but the molecular response has been unclear. MicroRNAs (miRNAs) are small noncoding and negative regulatory RNAs that are 20-24 nucleotides in length, which are involved in a wide range of biological processes. We took advantage of deep-sequencing techniques to accurately and comprehensively profile the kidney miRNA expression of grass carp after 8weeks of oral exposure to DBDPE. After mapping sequencing data to the genome and Expressed Sequence Tags (ESTs) of grass carp, we identified 493 miRNAs in the sequenced grass carp samples, which included 51 new miRNAs. The results indicated that 5 miRNAs were significantly down-regulated and 36 miRNAs were significantly up-regulated (FDR<0.001, 1.5-fold change) after DBDPE exposure. Real-time quantitative PCR (RT-qPCR) was performed on 4 miRNAs from the two samples, and the sequencing and RT-qPCR data were consistent. This study provides the first comprehensive identification of grass carp miRNAs, and the first expression analysis of grass carp miRNAs following DBDPE exposure. The results indicated that miRNAs have potential for use as biomarkers. PMID- 27266304 TI - Rapid synthesis of Ti-MCM-41 by microwave-assisted hydrothermal method towards photocatalytic degradation of oxytetracycline. AB - This study employed microwave-assisted hydrothermal method to synthesize Ti-MCM 41, which are mesoporous materials with a high surface area and excellent photocatalytic ability. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and ultraviolet-visible spectroscopy (UV-Vis) were employed. The XRD findings showed that Ti-MCM-41 exhibited a peak at 2theta of 2.2 degrees , which was attributed to the hexagonal MCM-41 structure. The BET (Brunauer Emmett-Teller) results agreed with the TEM findings that Ti-MCM-41 has a pore size of about 3-5nm and a high surface area of 883m(2)/g. FTIR results illustrated the existence of Si-O-Si and Si-O-Ti bonds in Ti-MCM-41. The appearance of Ti 2p peaks in the XPS results confirmed the FTIR findings that the Ti was successfully doped into the MCM-41 structure. Zeta (zeta)-potential results indicated that the iso-electric point (IEP) of Ti-MCM-41 was at about pH3.02. In this study, the photocatalytic degradation of oxytetracycline (OTC) at different pH was investigated under Hg lamp irradiation (wavelength 365nm). The rate constant (K'obs) for OTC degradation was 0.012min(-1) at pH3. Furthermore, TOC (total organic carbon) and high resolution LC-MS (liquid chromatography-mass spectrometry) analyses were conducted to elucidate the possible intermediate products and degradation pathway for OTC. The TOC removal efficiency of OTC degradation was 87.0%, 74.4% and 50.9% at pH3, 7 and 10, respectively. LC-MS analysis results showed that the degradation products from OTC resulted from the removal of functional groups from the OTC ring. PMID- 27266305 TI - Environmental application and ecological significance of nano-zero valent iron. AB - Toxicity studies considering both the bare and stabilized forms of zero valent iron nanoparticles (nZVI) could be timely, given that ecological risks identified are minimized through modification or with substitution of approaches in the synthesis, development and environmental application of the nanoparticles before succeeding to volume production. This review is focused on the fate, transport and toxicological implications of the bare nZVI and surface modified particles used for environmental applications. PMID- 27266306 TI - Non-thermal plasma treatment of Radix aconiti wastewater generated by traditional Chinese medicine processing. AB - The wastewater effluent from Radix aconiti processing, an important step in the production processes of traditional Chinese medicine (TCM), is a type of toxic wastewater and difficult to treat. Plasma oxidation methods have emerged as feasible techniques for effective decomposition of toxic organic pollutants. This study examined the performance of a plasma reactor operated in a dielectric barrier discharge (DBD) to degrade the effluent from R. aconiti processing. The effects of treatment time, discharge voltage, initial pH value and the feeding gas for the reactor on the degradation of this TCM wastewater were investigated. A bacterium bioluminescence assay was adopted in this study to test the toxicity of the TCM wastewater after non-thermal plasma treatment. The degradation ratio of the main toxic component was 87.77% after 60min treatment with oxygen used as feed gas and it was 99.59% when the initial pH value was 8.0. High discharge voltage and alkaline solution environment were beneficial for improving the degradation ratio. The treatment process was found to be capable of reducing the toxicity of the wastewater to a low level or even render it non-toxic. These experimental results suggested that the DBD plasma method may be a competitive technology for primary decomposition of biologically undegradable toxic organic pollutants in TCM wastewater. PMID- 27266307 TI - Do phytotoxic allelochemicals remain in ashes after burning Chrysanthemoides monilifera subsp. monilifera (boneseed)? AB - Australia is facing challenges in controlling Chrysanthemoides monilifera subsp. monilifera (boneseed). However, burning has achieved some success in this regard. We aimed to investigate the comparative phytotoxicity of boneseed dried powder and ashes (burnt at 450 degrees C and 250 degrees C). Phenolic compounds in powder and ashes were measured using Folin-Ciocalteu assay and HPLC. The phytotoxicity of boneseed powder and ash extracts was assessed through germination bioassay on Lactuca sativa and the phytotoxicity of litter and ashes was evaluated using field soil, both in growth chamber. Burning of boneseed reduced total phenolics in ashes of boneseed organs by 99% and 100% both at high and low temperatures. The four phenolic compounds that were detected in boneseed were either absent or at negligible levels in the ashes, with inversely related to temperature. Both boneseed ash extracts and litter ash-mediated soil significantly reduced phytotoxicity displaying increased germination, biometric and biochemical parameters of test species compared with unburnt powder extracts and litter powder-mediated soil respectively, with greater reduction of phytotoxicity found for ashes produced at the lower temperature. Interestingly, the ash extracts and litter ash-mediated soil were found to stimulate some of those parameters of the test species compared to control. There was no excessive reactive oxygen species (ROS) produced in test species exposed to ash extracts compared with unburnt powder extracts. These findings suggest that burning of boneseed is an appropriate method of weed control and that this approach will reduce phytotoxicity of this species on native plants. PMID- 27266308 TI - Microcystin accumulation and biochemical responses in the edible clam Corbiculaleana P. exposed to cyanobacterial crude extract. AB - We investigated the accumulation and effects of cyanobacterial crude extract (CCE) containing microcystins (MCs) on the edible clam Corbiculaleana P. Toxic effects were evaluated through the activity of antioxidant and detoxification enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione-S transferases (GSTs) from gills, foot, mantle and remaining soft tissues. Clams were exposed to CCE containing 400MUg MC-LReq/L for 10days and were then kept in toxin-free water for 5days. Clam accumulated MCs (up to 3.41+/-0.63MUg/g dry weight (DW) of unbound MC and 0.31+/-0.013MUg/g DW of covalently bound MC). Detoxification and antioxidant enzymes in different organs responded differently to CCE during the experiment. The activity of SOD, CAT, and GST in the gills and mantle increased in MC-treated clams. In contrast, CAT and GST activity was significantly inhibited in the foot and mostly only slightly changed in the remaining tissues. The responses of biotransformation, antioxidant enzyme activity to CCE and the fast elimination of MCs during depuration help to explain how the clam can survive for long periods (over a week) during the decay of toxic cyanobacterial blooms in nature. PMID- 27266309 TI - Lead toxicity thresholds in 17 Chinese soils based on substrate-induced nitrification assay. AB - The influence of soil properties on toxicity threshold values for Pb toward soil microbial processes is poorly recognized. The impact of leaching on the Pb threshold has not been assessed systematically. Lead toxicity was screened in 17 Chinese soils using a substrate-induced nitrification (SIN) assay under both leached and unleached conditions. The effective concentration of added Pb causing 50% inhibition (EC50) ranged from 185 to >2515mg/kg soil for leached soil and 130 to >2490mg/kg soil for unleached soil. These results represented >13- and >19 fold variations among leached and unleached soils, respectively. Leaching significantly reduced Pb toxicity for 70% of both alkaline and acidic soils tested, with an average leaching factor of 3.0. Soil pH and CEC were the two most useful predictors of Pb toxicity in soils, explaining over 90% of variance in the unleached EC50 value. The relationships established in the present study predicted Pb toxicity within a factor of two of measured values. These relationships between Pb toxicity and soil properties could be used to establish site-specific guidance on Pb toxicity thresholds. PMID- 27266310 TI - Sulfate reducing bacterial community and in situ activity in mature fine tailings analyzed by real time qPCR and microsensor. AB - Sulfate reducing bacteria (SRB) play significant roles in anaerobic environments in oil sands mature fine tailings (MFTs). Hydrogen sulfide (H2S) is produced during the biological sulfate reduction process. The production of toxic H2S is one of the concerns because it may hinder the landscape remediation efficiency of oil sands tailing ponds. In present study, the in situ activity and the community structure of SRB in MFT and gypsum amended MFT in two settling columns were investigated. Combined techniques of H2S microsensor and dissimilatory sulfite reductase beta-subunit (dsrB) genes-based real time quantitative polymerase chain reaction (qPCR) were applied to detect the in situ H2S and the abundance of SRB. A higher diversity of SRB and more H2S were observed in gypsum amended MFT than that in MFT, indicating a higher sulfate reduction activity in gypsum amended MFT; in addition, the activity of SRB varied as depth in both MFT and gypsum amended MFT: the deeper the more H2S produced. Long-term plans for tailings management can be assessed more wisely with the information provided in this study. PMID- 27266311 TI - Rapid degradation of dyes in water by magnetic Fe(0)/Fe3O4/graphene composites. AB - Magnetic Fe(0)/Fe3O4/graphene has been successfully synthesized by a one-step reduction method and investigated in rapid degradation of dyes in this work. The material was characterized by N2 sorption-desorption, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometer (VSM) measurements and X-ray photoelectron spectroscopy (XPS). The results indicated that Fe(0)/Fe3O4/graphene had a layered structure with Fe crystals highly dispersed in the interlayers of graphene, which could enhance the mass transfer process between Fe(0)/Fe3O4/graphene and pollutants. Fe(0)/Fe3O4/graphene exhibited ferromagnetism and could be easily separated and re-dispersed for reuse in water. Typical dyes, such as Methyl Orange, Methylene Blue and Crystal Violet, could be decolorized by Fe(0)/Fe3O4/graphene rapidly. After 20min, the decolorization efficiencies of methyl orange, methylene blue and crystal violet were 94.78%, 91.60% and 89.07%, respectively. The reaction mechanism of Fe(0)/Fe3O4/graphene with dyes mainly included adsorption and enhanced reduction by the composite. Thus, Fe(0)/Fe3O4/graphene prepared by the one-step reduction method has excellent performance in removal of dyes in water. PMID- 27266312 TI - Estimating emissions from crop residue open burning in China based on statistics and MODIS fire products. AB - With the objective of reducing the large uncertainties in the estimations of emissions from crop residue open burning, an improved method for establishing emission inventories of crop residue open burning at a high spatial resolution of 0.25 degrees *0.25 degrees and a temporal resolution of 1month was established based on the moderate resolution imaging spectroradiometer (MODIS) Thermal Anomalies/Fire Daily Level3 Global Product (MOD/MYD14A1). Agriculture mechanization ratios and regional crop-specific grain-to-straw ratios were introduced to improve the accuracy of related activity data. Locally observed emission factors were used to calculate the primary pollutant emissions. MODIS satellite data were modified by combining them with county-level agricultural statistical data, which reduced the influence of missing fire counts caused by their small size and cloud cover. The annual emissions of CO2, CO, CH4, nonmethane volatile organic compounds (NMVOCs), N2O, NOx, NH3, SO2, fine particles (PM2.5), organic carbon (OC), and black carbon (BC) were 150.40, 6.70, 0.51, 0.88, 0.01, 0.13, 0.07, 0.43, 1.09, 0.34, and 0.06Tg, respectively, in 2012. Crop residue open burning emissions displayed typical seasonal and spatial variation. The highest emission regions were the Yellow-Huai River and Yangtse Huai River areas, and the monthly emissions were highest in June (37%). Uncertainties in the emission estimates, measured as 95% confidence intervals, range from a low of within +/-126% for N2O to a high of within +/-169% for NH3. PMID- 27266313 TI - pH-dependent release characteristics of antimony and arsenic from typical antimony-bearing ores. AB - The pH-dependent leaching of antimony (Sb) and arsenic (As) from three typical Sb bearing ores (Banxi, Muli and Tongkeng Antimony Mine) in China was assessed using a pH-static leaching experiment. The pH changes of the leached solutions and pH dependent leaching of Sb and As occurred in different ways. For the Banxi and Muli Sb ores, alkaline conditions were more favorable for the release of Sb compared to neutral and acidic conditions, but the reverse was true for the pH dependent release of As. For the Tongkeng Sb ore, unlike the previous two Sb bearing ores, acidic conditions were more favorable for Sb release than neutral and alkaline conditions. The ores with lower Sb and As contents released higher percentages of their Sb and As after 16day leaching, suggesting that they are the largest potential sources of pollution. This work may provide key information on the geochemistry of Sb and As in the weathering zone. PMID- 27266314 TI - Sulfur-based autotrophic denitrification from the micro-polluted water. AB - Eutrophication caused by high concentrations of nutrients is a huge problem for many natural lakes and reservoirs. Removing the nitrogen contamination from the low C/N water body has become an urgent need. Autotrophic denitrification with the sulfur compound as electron donor was investigated in the biofilter reactors. Through the lab-scale experiment, it was found that different sulfur compounds and different carriers caused very different treatment performances. Thiosulfate was selected to be the best electron donor and ceramsite was chosen as the suitable carrier due to the good denitrification efficiency, low cost and the good resistibility against the high hydraulic loads. Later the optimum running parameters of the process were determined. Then the pilot-scale experiment was carried out with the real micro-polluted water from the West Lake, China. The results indicated that the autotrophic denitrification with thiosulfate as electron donor was feasible and applicable for the micro-polluted lake water. PMID- 27266315 TI - The potential application of red mud and soil mixture as additive to the surface layer of a landfill cover system. AB - Red mud, the by-product of aluminum production, has been regarded as a problematic residue all over the world. Its storage involves risks as evidenced by the Ajka red mud spill, an accident in Hungary where the slurry broke free, flooding the surrounding areas. As an immediate remediation measure more than 5cm thick red mud layer was removed from the flooded soil surface. The removed red mud and soil mixture (RMSM) was transferred into the reservoirs for storage. In this paper the application of RMSM is evaluated in a field study aiming at re utilizing waste, decreasing cost of waste disposal and providing a value-added product. The purpose was to investigate the applicability of RMSM as surface layer component of landfill cover systems. The field study was carried out in two steps: in lysimeters and in field plots. The RMSM was mixed at ratios ranging between 0 and 50% w/w with low quality subsoil (LQS) originally used as surface layer of an interim landfill cover. The characteristics of the LQS+RMSM mixtures compared to the subsoil (LQS) and the RMSM were determined by physical-chemical, biological and ecotoxicological methods. The addition of RMSM to the subsoil (LQS) at up to 20% did not result any ecotoxic effect, but it increased the water holding capacity. In addition, the microbial substrate utilization became about triple of subsoil (LQS) after 10months. According to our results the RMSM mixed into subsoil (LQS) at 20% w/w dose may be applied as surface layer of landfill cover systems. PMID- 27266316 TI - Computer simulation of the coagulation of suspended solids - The applicability of the Muller-Smoluchowski theory. AB - The results of studies carried out using a computer programme simulating the coagulation of suspensions containing spherical sol particles and spherical coagulant particles are reported. The influence of the degree of dispersion of the system on the coagulation reaction kinetics was investigated. The obtained results of kinetic studies were tested in the light of classical Muller Smoluchowski equations. The influence of the physical properties of the coagulant, such as size, density and mass, on the coagulation rate was tested. It was found that within the range described in this paper, the rate of the simulated coagulation process fulfils both the kinetic equation of a first-order reaction, and the kinetic equation of a second-order reaction. Within the tested range, a significant influence of the mass and size of the coagulant on the coagulation rate was ascertained. The kinetic Muller-Smoluchowski dependence is fulfilled in a broader range of the degree of dispersion, when the coagulant particle mass and the sol particle mass are equal. When the particle mass increases with an increase in the particle radius, the coagulation rate increases faster that it would result from the Muller's dependence. PMID- 27266317 TI - Positively charged microporous ceramic membrane for the removal of Titan Yellow through electrostatic adsorption. AB - To develop a depth filter based on the electrostatic adsorption principle, positively charged microporous ceramic membrane was prepared from a diatomaceous earth ceramic membrane. The internal surface of the highly porous ceramic membrane was coated with uniformly distributed electropositive nano-Y2O3 coating. The dye removal performance was evaluated through pressurized filtration tests using Titan Yellow aqueous solution. It showed that positively charged microporous ceramic membrane exhibited a flow rate of 421L/(m(2).hr) under the trans-membrane pressure of 0.03bar. Moreover it could effectively remove Titan Yellow with feed concentration of 10mg/L between pH3 to 8. The removal rate increased with the enhancement of the surface charge properties with a maximum rejection of 99.6%. This study provides a new and feasible method of removing organic dyes in wastewater. It is convinced that there will be a broad market for the application of charged ceramic membrane in the field of dye removal or recovery from industry wastewater. PMID- 27266318 TI - Distribution and transportation of mercury from glacier to lake in the Qiangyong Glacier Basin, southern Tibetan Plateau, China. AB - The Tibetan Plateau is home to the largest aggregate of glaciers outside the Polar Regions and is a source of fresh water to 1.4 billion people. Yet little is known about the transportation and cycling of Hg in high-elevation glacier basins on Tibetan Plateau. In this study, surface snow, glacier melting stream water and lake water samples were collected from the Qiangyong Glacier Basin. The spatiotemporal distribution and transportation of Hg from glacier to lake were investigated. Significant diurnal variations of dissolved Hg (DHg) concentrations were observed in the river water, with low concentrations in the morning (8:00am 14:00pm) and high concentrations in the afternoon (16:00pm-20:00pm). The DHg concentrations were exponentially correlated with runoff, which indicated that runoff was the dominant factor affecting DHg concentrations in the river water. Moreover, significant decreases of Hg were observed during transportation from glacier to lake. DHg adsorption onto particulates followed by the sedimentation of particulate-bound Hg (PHg) could be possible as an important Hg removal mechanism during the transportation process. Significant decreases in Hg concentrations were observed downstream of Xiao Qiangyong Lake, which indicated that the high-elevation lake system could significantly affect the distribution and transportation of Hg in the Qiangyong Glacier Basin. PMID- 27266319 TI - Effects of pentachlorophenol on the detoxification system in white-rumped munia (Lonchura striata). AB - Pentachlorophenol (PCP), a priority pollutant due to its persistence and high toxicity, has been used worldwide as a pesticide and biocide. To understand the adverse effects of PCP, adult male white-rumped munias (Lonchura striata) were orally administrated commercial PCP mixed with corn oil at dosages of 0, 0.05, 0.5, and 5mg/(kg.day) for 42day. Gas chromatography-mass spectrometry (GC-MS) analysis found that PCP was preferentially accumulated in the kidney rather than in the liver and muscle in all exposure groups. To examine the function of CYP1A in pollutant metabolism, we isolated two full-length cDNA fragments (designated as CYP1A4 and CYP1A5) from L. striata liver using reverse transcription polymerase chain reaction and rapid amplification of cDNA ends. PCP induced the expression of CYP1A5, although no obvious change was observed in CYP1A4 expression. Furthermore, PCP significantly elevated the activities of ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase and decreased the activity of benzyloxy-trifluoromethyl-coumarin, with no significant responses observed in benzyloxyresorufin O-debenzylase. PCP induced significant changes in antioxidant enzyme (superoxide dismutase and catalase) activities and malondialdehyde content, but decreased glutathione peroxidase (GSH-Px) and glutathione S-transferase activities and GSH content in the liver of L. striata. The present study demonstrated that PCP had hepatic toxic effects by affecting CYP1As and anti-oxidative status. PMID- 27266320 TI - High-performance size exclusion chromatography with a multi-wavelength absorbance detector study on dissolved organic matter characterisation along a water distribution system. AB - This study examined the associations between dissolved organic matter (DOM) characteristics and potential nitrification occurrence in the presence of chloramine along a drinking water distribution system. High-performance size exclusion chromatography (HPSEC) coupled with a multiple wavelength detector (200 280nm) was employed to characterise DOM by molecular weight distribution, bacterial activity was analysed using flow cytometry, and a package of simple analytical tools, such as dissolved organic carbon, absorbance at 254nm, nitrate, nitrite, ammonia and total disinfectant residual were also applied and their applicability to indicate water quality changes in distribution systems were also evaluated. Results showed that multi-wavelength HPSEC analysis was useful to provide information about DOM character while changes in molecule weight profiles at wavelengths less than 230nm were also able to be related to other water quality parameters. Correct selection of the UV wavelengths can be an important factor for providing appropriate indicators associated with different DOM compositions. DOM molecular weight in the range of 0.2-0.5kDa measured at 210nm correlated positively with oxidised nitrogen concentration (r=0.99), and the concentrations of active bacterial cells in the distribution system (r=0.85). Our study also showed that the changes of DOM character and bacterial cells were significant in those sampling points that had decreases in total disinfectant residual. HPSEC-UV measured at 210nm and flow cytometry can detect the changes of low molecular weight of DOM and bacterial levels, respectively, when nitrification occurred within the chloraminated distribution system. PMID- 27266321 TI - Occurrence and impact of polychlorinated dibenzo-p-dioxins/dibenzofurans in the air and soil around a municipal solid waste incinerator. AB - To assess the influence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) on the environment in the vicinity of municipal solid waste incinerators (MSWIs), we determined the levels of PCDD/Fs in air and soil samples collected around a MSWI, which is the largest in China. The International Toxicity Equivalency Quantity (I-TEQ) concentrations of PCDD/Fs in air samples were from 0.0300 to 1.03pgI-TEQ/m(3) (0.445-13.6pg/m(3)), with an average of 0.237pgI-TEQ/m(3), while in soil samples they ranged from 0.520 to 3.40pgI-TEQ/g (2.41-88.7pg/g) with an average of 1.49pgI-TEQ/g. The concentrations of PCDD/Fs in air and soil samples were comparable to other areas, and PeCDFs were the dominant contributors, which was different from stack gas homologue patterns. Multivariate statistical analysis showed that PCDD/Fs emission from the MSWI did not directly affect the profiles of PCDD/Fs in air and soils, so that vehicles and unidentified emission sources should be considered. The daily inhalation levels of PCDD/Fs for children (0.0110 to 0.392pgI-TEQ/(kg.day) and adults (0.00600 to 0.221pgI-TEQ/(kg.day) near the MSWI were lower than the tolerable daily intake of 1.00 to 4.00pg WHO-TEQ/(kg.day), but in winter the values were higher than in summer. These results can be used as basic data for assessing the risk of PCDD/Fs exposure in residents living around this MSWI, and more monitoring programs and studies should be carried out around MSWIs. PMID- 27266322 TI - The biological effect of metal ions on the granulation of aerobic granular activated sludge. AB - As a special biofilm structure, microbial attachment is believed to play an important role in the granulation of aerobic granular activated sludge (AGAS). This experiment was to investigate the biological effect of Ca(2+), Mg(2+), Cu(2+), Fe(2+), Zn(2+), and K(+) which are the most common ions present in biological wastewater treatment systems, on the microbial attachment of AGAS and flocculent activated sludge (FAS), from which AGAS is always derived, in order to provide a new strategy for the rapid cultivation and stability control of AGAS. The result showed that attachment biomass of AGAS was about 300% higher than that of FAS without the addition of metal ions. Different metal ions had different effects on the process of microbial attachment. FAS and AGAS reacted differently to the metal ions as well, and in fact, AGAS was more sensitive to the metal ions. Specifically, Ca(2+), Mg(2+), and K(+) could increase the microbial attachment ability of both AGAS and FAS under appropriate concentrations, Cu(2+), Fe(2+), and Zn(2+) were also beneficial to the microbial attachment of FAS at low concentrations, but Cu(2+), Fe(2+), and Zn(2+) greatly inhibited the attachment process of AGAS even at extremely low concentrations. In addition, the acylated homoserine lactone (AHL)-based quorum sensing system, the content of extracellular polymeric substances and the relative hydrophobicity of the sludges were greatly influenced by metal ions. As all these parameters had close relationships with the microbial attachment process, the microbial attachment may be affected by changes of these parameters. PMID- 27266323 TI - Phosphate recovery from anaerobic digester effluents using CaMg(OH)4. AB - Dolomite lime (DL) (CaMg(OH)4) was used as an economical source of Mg(2+) for the removal and recovery of phosphate from an anaerobic digester effluent of a municipal wastewater treatment plant (MWWTP) wastewater. Batch precipitation results determined that phosphate was effectively reduced from 87 to less than 4mg-P/L when the effluent water was mixed with 0.3g/L of DL. The competitive precipitation mechanisms of different solids in the treatment system consisting of Ca(2+)-Mg(2+)-NH4(+)-PO4(3-)CO3(2-) were determined by comparing model predictions with experimental results. Thermodynamic model calculations indicated that hydroxyapatite (Ca10(PO4)6(OH)2), Ca4H(PO4)3?3H2O, Ca3(PO4)2(beta), and Ca3(PO4)2(am2) were more stable than struvite (MgNH4PO3?6H2O) and calcite (CaCO3). However, X-ray diffraction (XRD) analysis determined the formation of struvite and calcite minerals in the treated effluent. Kinetic experimental results showed that most of the phosphate was removed from synthetic effluent containing NH4(+) within 2hr, while only 20% of the PO4(3-) was removed in the absence of NH4(+) after 24hr of treatment. The formation of struvite in the DL treated effluent was due to the rapid precipitation rate of the mineral. The final pH of the DL-treated effluent significantly influenced the mass ratio of struvite to calcite in the precipitates. Because more calcite was formed when the pH increased from 8.4 to 9.6, a pH range of 8.0-8.5 should be used to produce solid with high PO4(3-) content. This study demonstrated that DL could be used for effective removal of phosphate from the effluent and that resultant precipitates contained high content of phosphate and ammonium. PMID- 27266324 TI - Biochar: A review of its impact on pesticide behavior in soil environments and its potential applications. AB - Biochar is produced from the pyrolysis of carbon-rich plant- and animal-residues under low oxygen and high temperature conditions and has been increasingly used for its positive role in soil compartmentalization through activities such as carbon sequestration and improving soil quality. Biochar is also considered a unique adsorbent due to its high specific surface area and highly carbonaceous nature. Therefore, soil amendments with small amounts of biochar could result in higher adsorption and, consequently, decrease the bioavailability of contaminants to microbial communities, plants, earthworms, and other organisms in the soil. However, the mechanisms affecting the environmental fate and behavior of organic contaminants, especially pesticides in biochar-amended soil, are not well understood. The purpose of this work is to review the role of biochar in primary processes, such as adsorption-desorption and leaching of pesticides. Biochar has demonstrable effects on the fate and effects of pesticides and has been shown to affect the degradation and bioavailability of pesticides for living organisms. Moreover, some key aspects of agricultural and environmental applications of biochar are highlighted. PMID- 27266325 TI - Corrigendum to "Silver nanoparticles tolerant bacteria from sewage environment" [J. Environ. Sci. (2011) 23 (2) 346-352]. PMID- 27266326 TI - Indian scheme to reduce antibiotic misuse is failing because of widespread ignorance, say pharmacists. PMID- 27266328 TI - Are firefighters able to perform intraosseous access and start fluid resuscitation in an anaphylactic patient? PMID- 27266329 TI - Successful treatment of a pulmonary embolism with low dose of tissue plasminogen activator after thoracic surgery. PMID- 27266327 TI - Triggering receptor expressed on myeloid cells and 5'adenosine monophosphate activated protein kinase in the inflammatory response: a potential therapeutic target. AB - INTRODUCTION: The events in the cellular and molecular signaling triggered during inflammation mitigate tissue healing. The metabolic check-point control mediated by 5'-adenosine monophosphate-activated protein kinase (AMPK) is crucial for switching the cells into an activated state capable of mediating inflammatory events. The cell metabolism involved in the inflammatory response represents a potential therapeutic target for the pharmacologic management of inflammation. Areas covered: In this article, a critical review is presented on triggering receptor expressed on myeloid cell (TREM) receptors and their role in the inflammatory responses, as well as homeostasis between different TREM molecules and their regulation. Additionally, we discussed the relationship between TREM and AMPK to identify novel targets to limit the inflammatory response. Literature search was carried out from the National Library of Medicine's Medline database (using PubMed as the search engine) and Google Scholar and identified relevant studies up to 30 March 2016 using inflammation, TREM, AMPK, as the key words. Expert commentary: The prevention of phenotype switching of immune cells during inflammation by targeting AMPK and TREM-1 could be beneficial for developing novel management strategies for inflammation and associated complications. PMID- 27266331 TI - Sweating the assets of flavin cofactors: new insight of chemical versatility from knowledge of structure and mechanism. AB - Flavins are arguably one of the most versatile cofactors by virtue of the reactivity of the isoalloxazine ring system. A varied catalogue of reactions for the diverse family of flavoenzymes has been reported, leading to unifying concepts in (long-range) electron transfer, oxygen activation, photochemistry and substrate redox reactions. Recent examples of unprecedented flavin chemistry have been reported that uncover hidden depths of the flavoenzyme chemical repertoire. These include ring expansion of flavin through prenylation and formation of the superoxidized flavin-N5 oxide species. These and other new flavin based species are reviewed here and suggest further exciting discoveries await the flavoenzymology field. PMID- 27266330 TI - Structure and mechanism of assembly line polyketide synthases. AB - Assembly line polyketide synthases (PKSs) are remarkable biosynthetic machines with considerable potential for structure-based engineering. Several types of protein-protein interactions, both within and between PKS modules, play important roles in the catalytic cycle of a multimodular PKS. Additionally, vectorial biosynthesis is enabled by the energetic coupling of polyketide chain elongation to the channeling of intermediates between successive modules. A combination of high-resolution analysis of smaller PKS components and lower resolution characterization of intact modules and bimodules has yielded insights into the structure and organization of a prototypical assembly line PKS. This review discusses our understanding of key structure-function relationships in this family of megasynthases, along with a recap of key unanswered questions in the field. PMID- 27266333 TI - Qualitative and quantitative determination of R-phycoerythrin from Halymenia floresia (Clemente) C. Agardh by polyacrylamide gel using electrophoretic elution technique. AB - R-Phycoerythrin is one of the phycobiliproteins widely found in seaweeds. In this study, we have shown to extract and purify R-Phycoerythrin from the south east cost Indian red seaweed Halymenia floresia. R-Phycoerythrin was extracted in 50mM phosphate buffer (pH 7.0). The preparative native PAGE purification was employed alternative to the chromatography and therefore can be scaled up efficiently. Both the yield and the purity of R-Phycoerythrin are very effective. The purified R-Phycoerythrin showed a single band on the examination by native PAGE electrophrosis. SDS-PAGE analysis showed five bands at 16kDa, 21kDa, 30kDa, 39kDa and 47kDa which corresponds to the alpha, beta and gamma', gamma and alphabeta subunits. This preparative method for R-Phycoerythrin purification can offer a reference for R-Phycoerythrin purification from other marine red macro algae. PMID- 27266332 TI - Graphitic carbon nitride as high-resolution stationary phase for gas chromatographic separations. AB - This work presents the first example of utilization of graphitic carbon nitride (g-C3N4) as stationary phase for capillary gas chromatographic (GC) separations. The statically coated g-C3N4 column showed the column efficiencies of 3760 plates/m and weak polarity. Its resolving capability and retention behaviours were investigated by using the Grob test mixture, and mixtures of diverse types of analytes, and structural and positional isomers. The results showed superior separation performance of the g-C3N4 stationary phase for some critical analytes and preferential retention for aromatic analytes. Specifically, it exhibited high resolution capability for aromatic and aliphatic isomers such as methylnaphthalenes and dimethylnaphthalenes, phenanthrene and anthracene and alkane isomers. In addition, g-C3N4 column showed excellent thermal stability up to 280 degrees C and good repeatability with relative standard deviation (RSD) values less than 0.09% for intra-day, below 0.23% for inter-day and in the range of 1.9-8.4% for between-column, respectively. The advantageous separation performance shows the potential of g-C3N4 and related materials as stationary phase in GC and other separation technologies. PMID- 27266334 TI - Mixed hemimicelles solid-phase extraction of cephalosporins in biological samples with ionic liquid-coated magnetic graphene oxide nanoparticles coupled with high performance liquid chromatographic analysis. AB - A novel mixed hemimicelles solid phase extraction based on magnetic graphene oxide (Fe3O4/GO) and ionic liquid (IL) was developed for the simultaneous extraction and determination of trace cephalosporins in spiked human urine. The high surface area and excellent adsorption capacity of the graphene oxide after modification with1-hexadecyl-3-methylmidazoliumbromide(C16mimBr) were utilized adequately in the solid phase extraction(SPE) process. A comprehensive study of the parameters affecting the extraction recovery, such as the zeta-potential of magnetic graphene oxide, amounts of magnetic graphene oxide and surfactant, pH of solution, ionic strength, extraction time, and desorption condition were optimized. A comparative study on the use of different surfacant-coated Fe3O4/GO NPs as sorbents was presented. Good linearity (R(2)>0.9987) for all calibration curves was obtained. The LODs were ranged between 0.6 and 1.9ng mL(-1) for the cephalosporins and the LOQs were 1.5 to 5.5, respectively. Satisfactory recoveries(84.3% to 101.7%)and low relative standard deviations from 1.7% to 6.3% in biological matrices were achieved. The mixed hemimicelles magnetic SPE (MSPE) method based on ILs and Fe3O4/GO NPs magnetic separation has ever been successfully used for pretreatment of complex biological samples. PMID- 27266335 TI - Separation of enantiomers on chiral stationary phase based on cellulase: Effect of preparation method and silica particle diameters on chiral recognition ability. AB - Cellulase (Cel) was immobilized onto aminopropyl-silica gels via its amino and carboxy groups, respectively, using N,N'-disuccinimidyl carbonate, and 1-ethyl-3 (3'-dimethylaminopropyl)carbodimide and N-hydroxysulfosuccinimide. They were termed N-Cel and C-Cel, respectively. Despite their smaller retention factors on a C-Cel column, the enantioseparation factors and resolution of beta-blockers, propranolol, alprenolol, oxprenolol and pindolol, were similar with N- and C-Cel columns. In addition, C-Cel was prepared using aminopropyl-silica gels, whose nominal particle diameters were 5 and 3, and 2.1MUm, respectively. A C-Cel column prepared with 2.1-MUm aminopropyl-silica gels gave the highest enantioselectivity and column efficiency among three C-Cel columns. Furthermore, the influence of N,N-dimethyl-n-octylamine (DMOA) or cellobiose concentrations on the retentivity and enantioselectivity for beta-blockers on a C-Cel column was investigated. The results indicate that single-site competition of beta-blockers with DMOA or cellobiose on the catalytic binding site of Cel and the further bindings at the secondary site in a non-competitive fashion could occur. Furthermore, the enantioselective bindings of beta-blockers could occur at the catalytic biding cite of Cel and at the secondary binding site. PMID- 27266336 TI - Theoretical repeatability assessment without repetitive measurements in gradient high-performance liquid chromatography. AB - This paper puts forward a time and material-saving method for evaluating the repeatability of area measurements in gradient HPLC with UV detection (HPLC-UV), based on the function of mutual information (FUMI) theory which can theoretically provide the measurement standard deviation (SD) and detection limits through the stochastic properties of baseline noise with no recourse to repetitive measurements of real samples. The chromatographic determination of terbinafine hydrochloride and enalapril maleate is taken as an example. The best choice of the number of noise data points, inevitable for the theoretical evaluation, is shown to be 512 data points (10.24s at 50 point/s sampling rate of an A/D converter). Coupled with the relative SD (RSD) of sample injection variability in the instrument used, the theoretical evaluation is proved to give identical values of area measurement RSDs to those estimated by the usual repetitive method (n=6) over a wide concentration range of the analytes within the 95% confidence intervals of the latter RSD. The FUMI theory is not a statistical one, but the "statistical" reliability of its SD estimates (n=1) is observed to be as high as that attained by thirty-one measurements of the same samples (n=31). PMID- 27266337 TI - Quantitative determination of hydroxy polycylic aromatic hydrocarbons as a biomarker of exposure to carcinogenic polycyclic aromatic hydrocarbons. AB - A high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS) method was developed for quantitative analysis of hydroxy polycyclic aromatic hydrocarbons (OH-PAHs). Four hydroxy metabolites of known and suspected carcinogenic PAHs (benzo[a]pyrene (B[a]P), benz[a]anthracene (B[a]A), and chrysene (CRY)) were selected as suitable biomarkers of PAH exposure and associated risks to human health. The analytical method included enzymatic deconjugation, liquid - liquid extraction, followed by derivatization with methyl N-(trimethylsilyl) trifluoroacetamide and instrumental analysis. Photo-induced oxidation of target analytes - which has plagued previously published methods - was controlled by a combination of minimizing exposure to light, employing an antioxidant (2-mercaptoethanol) and utilizing a nitrogen atmosphere. Stability investigations also indicated that conjugated forms of the analytes are more stable than the non-conjugated forms. Accuracy and precision of the method were 77.4-101% (<4.9% RSD) in synthetic urine and 92.3-117% (<15% RSD) in human urine, respectively. Method detection limits, determined using eight replicates of low level spiked human urine, ranged from 13 to 24pg/mL. The method was successfully applied for analysis of a pooled human urine sample and 78 mouse urine samples collected from mice fed with PAH-contaminated diets. In mouse urine, greater than 94% of each analyte was present in its conjugated form. PMID- 27266338 TI - Switch from infliximab to infliximab biosimilar: efficacy and safety in a cohort of patients with different rheumatic diseasesResponse to: Nikiphorou E, Kautiainen H, Hannonen P, et al. Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (infliximab) in patients with established rheumatic disease. Report of clinical experience based on prospective observational data. Expert Opin Biol Ther. 2015;15:1677-1683. PMID- 27266339 TI - Hepatoprotective Effects of Soybean Embryo by Enhancing Adiponectin-Mediated AMP Activated Protein Kinase alpha Pathway in High-Fat and High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD), which is characterized by >5% deposition of triglycerides in hepatocytes, is often referred as a major risk factor for obesity, type 2 diabetes, and hypertension. We investigated the hepatoprotective effect of whole soybean embryos containing bioactive substances such as isoflavones and soyasaponins. For this study, mice were randomly allocated into four groups that were fed different diets for 10 weeks: normal diets and high-fat and high-cholesterol diets (HD), and HD with 10% or 20% soybean embryo powder (10SE-HD and 20SE-HD). Hepatic superoxide dismutase and glutathione peroxidase activity of the experimental groups increased during the period of the study (P < .05). Hepatic mRNA expressions of tumor necrosis factor alpha, nuclear factor (erythroid-derived 2)-like 2, and Caspase 3 were decreased when soybean embryos were increased in the mice's diets. Both of the soybean embryo-treated groups showed significantly decreased serum and liver triglyceride and total cholesterol. Adiponectin, AMP-activated protein kinase (AMPK) alpha, hydroxymethylglutaryl-CoA reductase, sterol regulatory element-binding protein 1c, fatty acid synthase, and apolipoprotein B mRNA expressions were decreased in the mice that were fed soybean embryos. We suggest that the regular supplementation of soybean embryos might be a useful treatment for preventing NAFLD and associated complications through upregulation of adiponectin-mediated AMPKalpha pathway parameters, which are implicated in antioxidant, anti inflammatory, and lipid metabolism activities. PMID- 27266340 TI - Impact of Selenium Supplementation in Neutropenia and Immunoglobulin Production in Childhood Cancer Patients. AB - Essential to human health, selenium (Se) has enzymatic functions of fundamental importance to human biology due to its effects on DNA damage repair, its antioxidant properties, and cancer prevention. The best studied relationships between Se and the immune system is its role in the functions of neutrophils and of lymphocytes. Despite these observations, it is not yet clear by which mechanism Se is able to modify the immune status. This was a double-blind, crossover study: Group 1 received Se and Group 2 received placebo (30 days). After this, Group 1 received placebo and Group 2 received Se (30 days). Every 30 days, blood samples were collected for white blood cell count, red blood cell count, and Ig level measurement (IgA, IgG, IgE, IgM). Of the 36 patients, 17 were suffering from leukemia/lymphomas (LL) and 19 from solid tumors (ST). In the ST group's leukogram, a significant increase in neutrophils was observed after Se usage (P = .0192). During the analyzed period, Se minimized the triggering of neutropenia cases in both groups. IgA and IgG levels in ST patients were significantly higher than those identified in LL patients after Se usage (P = .0051 and P = .0055). For IgA, a significant increase in its production, after Se usage, was observed in the ST group when compared to the LL (P = .0011). The same did not occur to the IgM and IgE immunoglobulins. In our study, the supplementation with Se reduced the neutropenic cases (LL and ST patients) and reduced IgG and IgA levels in LL and increased in ST group. PMID- 27266341 TI - Aqueous Extraction of Citrus unshiu Peel Induces Proangiogenic Effects Through the FAK and ERK1/2 Signaling Pathway in Human Umbilical Vein Endothelial Cells. AB - Citrus unshiu peel has been used empirically as a traditional medicine to improve bronchial asthma and blood circulation in northeast Asian nations, including Korea, Japan, and China. In this study, we report the proangiogenic effects of the aqueous extract of Citrus unshiu peel (AECUP). In human umbilical vein endothelial cells, AECUP significantly induced cellular migration and capillary tube formation. We also demonstrated that AECUP markedly increased the phosphorylation of FAK and ERK1/2 through the integrin signaling pathway. Additionally, we identified that narirutin and hesperidin were major constituents of AECUP and both showed proangiogenic effects, but at different levels. Collectively, these results suggest that the AECUP may have potential as a therapeutic agent for improving angiogenic functions with reduced harmful side effects. PMID- 27266342 TI - Reliability of Malondialdehyde Measurements as a Marker of Oxidative Stress in Pediatrics. PMID- 27266344 TI - Classification of cancers based on copy number variation landscapes. AB - Genomic alterations in DNA can cause human cancer. DNA copy number variants (CNV), as one of the types of DNA mutations, have been considered to be associated with various human cancers. CNVs vary in size from 1bp up to one complete chromosome arm. In order to understand the difference between different human cancers on CNVs, in this study, we developed a method to computationally classify six human cancer types by using only CNV level values. The CNVs of 23,082 genes were used as features to construct the classifier. Then the features are carefully selected by mRMR (minimum Redundancy Maximum Relevance Feature Selection) and IFS (Incremental Feature Selection) methods. An accuracy of over 0.75 was reached by using only the CNVs of 19 genes based on Dagging method in 10 fold cross validation. It was indicated that these 19 genes may play important roles in differentiating cancer types. We also analyzed the biological functions of several top genes within the 19 gene list. The statistical results and biological analysis of these genes from this work might further help understand different human cancer types and provide guidance for related validation experiments. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. PMID- 27266345 TI - [Suggestion to improve the quality of paper writing for clinical research publication]. PMID- 27266343 TI - Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes. AB - BACKGROUND: The dominant feature in neurodegenerative diseases is protein aggregations that lead to neuronal loss. Immunotherapies using antibodies or antibody fragments to target the aggregations are a highly perused approach. The molecular mechanisms underlying the amyloid-based immunotherapy are complex. Deciphering the properties of amyloidogenic proteins responsible for these diseases is essential to obtain insights into antibody recognition of the amyloid antigens. SCOPE OF REVIEW: We systematically explore all available crystal structures of antibody-amyloid complexes related to neurodegenerative diseases, including antibodies that recognize the Abeta peptide, tau protein, prion protein, alpha-synuclein, huntingtin protein (mHTT), and polyglutamine. MAJOR CONCLUSIONS: We found that antibodies mostly use the conformational selection mechanism to recognize the highly flexible amyloid antigens. In particular, solanezumab bound to Abeta12-28 tripeptide motif conformation (F19F20A21), which is shared with the Abeta42 fibril. This motif, which is trapped by the antibody, may provide the missing link in amyloid formation. Water molecules often bridge between the antibody and amyloid, contributing to the recognition. GENERAL SIGNIFICANCE: This paper provides the structural basis for antibody recognition of amyloidogenic proteins. The analysis and discussion of known structures are expected to help in the design and optimization of antibodies in neurodegenerative diseases. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang. PMID- 27266346 TI - [Factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome]. AB - OBJECTIVE: To explore the factors influencing glucose metabolism in young obese subjects with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 106 young obese subjects[18-44 years old, body mass index (BMI) >=30 kg/m(2)]were enrolled and divided into two groups based on full-night polysomnography (PSG), OSAHS group[apnea hypopnea index (AHI) >=5 events/h]and non-OSAHS group (AHI<5 events/h). Oral glucose tolerance-insulin releasing test (OGTT-IRT) was performed and serum glycosylated hemoglobin A1 (HbA1c) levels were measured after an overnight fast. Homeostasis model assessment-IR (HOMA-IR), Matsuda insulin sensitivity index (MI), homeostasis model assessment-beta (HOMA beta), the early phase insulinogenic index (DeltaI(30)/DeltaG(30)), total area under the curve of insulin in 180 minutes (AUC-I180) and oral disposition index (DIo) were calculated to evaluate insulin resistance and pancreatic beta cell function. Stepwise multiple linear regressions were conducted to determine the independent linear correlation of glucose measurements with PSG parameters. RESULTS: Prevalence of diabetes was higher in OSAHS than in non-OSAHS group (22.0% vs 4.3%, P=0.009). OGTT 0, 30, 60 min glucose and HbA1c levels were higher in OSAHS group than those in non-OASHS group (all P<0.05). DIo were lower in OSAHS group than those in non-OASHS group (P=0.024), HOMA-IR, MI, HOMA-beta, DeltaI(30)/DeltaG(30), and AUC-I(180) were similar between two groups (all P>0.05). In stepwise multiple linear regressions, OGTT 0, 30 and 60 min glucose were positively correlated with oxygen desaturation index (ODI) (beta=0.243, 0.273 and 0.371 respectively, all P<0.05). HOMA-beta was negatively correlated with AHI (beta=-0.243, P=0.011). DIo was negatively correlated with ODI (beta= 0.234, P=0.031). CONCLUSION: OSAHS worsens glucose metabolism and compensatory pancreatic beta-cell function in young obese subjects, which could probably be attributed to sleep apnea related oxygen desaturation during sleep. PMID- 27266347 TI - [Relationship between expression of HDAC2, IL-8, TNF-alpha in lung adenocarcinoma tissues and smoking]. AB - OBJECTIVE: To investigate the relationship between the expression of histone acetylation enzyme 2 (HDAC2), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) in lung adenocarcinoma tissues and smoking. METHODS: A total of 73 cases of lung adenocarcinoma confirmed by pathological examination after surgical removals were collected in the First Affiliated Hospital and Affiliated Tumor Hospital of Guangxi Medical University from April 2014 to March 2015. All patients received preoperative lung function test. Lung adenocarcinoma and para cancer tissues were cut by the sharp blade and stored in liquid nitrogen and the sampling time was less than 30 minutes. Smokers were defined as people who had smoked more than 100 cigarettes or inhaled the smoke of cigarettes at least one day a week (more than 15 minutes every day) more than three years. According to the lung function and whether smoking or not, the cases of lung adenocarcinoma were divided into three groups: smoking without chronic obstructive pulmonary disease (COPD) group (33 cases), without smoking and COPD group (19 cases), smoking with COPD group (21 cases). The levels of HDAC2, IL-8 and TNF-alpha mRNA in lung adenocarcinoma and para-cancer tissues of groups were detected by real time polymerase chain reaction (PCR) and the expression of HDAC2 protein was detected by Western blotting, and statistical analysis was carried out. RESULTS: The expression of HDAC2, IL-8 and TNF-alpha in lung adenocarcinoma tissues and TNM stage of lung adenocarcinoma showed no significant differences with respect to age and gender (P>0.05). Compared with the para-cancer tissues of 73 cases, the expression of HDAC2 at mRNA and protein levels in lung adenocarcinoma tissues were significantly lower (t=4.15, 8.006, all P<0.01). and the content of IL-8 and TNF-alpha at mRNA levels were increased (t=-4.252, -5. 576, all P<0.01). The expression of HDAC2 mRNA and protein in lung adenocarcinoma tissues in smoking without COPD group and smoking with COPD group were significantly lower than in without smoking and COPD group (0.38+/-0.11, 0.35+/-0.12 vs 0.45+/-0.10 and 0.26+/-0.09, 0.24+/-0.06 vs 0.33+/-0.10; all P<0.05), and it was the lowest expression in smoking with COPD group. IL-8 and TNF-alpha at mRNA levels in lung adenocarcinoma tissues in smoking without COPD group and smoking with COPD group were significantly higher than in without smoking and COPD group (0.96+/-0.19, 1.10+/-0.18 vs 0.71+/-0.13 and 0.62+/-0.21, 0.64+/-0.20 vs 0.45+/-0.14; all P<0.05), and the up-regulation was more obvious in smoking with COPD group. The TNM stage of lung adenocarcinoma in smoking group (smoking without COPD group and smoking with COPD group) was higher than without smoking group (without smoking and COPD group)(P=0.038). CONCLUSION: HDAC2 is down-regulated and IL-8, TNF-alpha are up-regulated in lung adenocarcinoma tissues. They are influenced by smoking and especially when combined with chronic obstructive pulmonary disease. PMID- 27266348 TI - [The clinical characteristics analysis of Escherichia coli bloodstream infection]. AB - OBJECTIVE: To explore the clinical features of Escherichia coli bloodstream infection. METHODS: The clinical data of underlying diseases, antimicrobial susceptibility, temperature at blood sampling, results of routine blood tests, venous catheterization, therapy and prognosis of Escherichia coli bloodstream infection in the First Affiliated Hospital of Soochow University from January 2007 to December 2014 were analyzed retrospectively. The pathogens were routinely isolated and identified. Susceptibilities against antimicrobial agents were determined by Kirby-Bauer methods. RESULTS: All patients had at least one underlying disease. Most of the basic diseases were hematological malignancies, malignant solid tumors, pneumonia and so on. Body temperature was normal in 40 patients (6.4%), fever in 587 patients (93.5%) and low temperature in 1 patient. There were 252 patients with leukopenia (40.1%), 237 patients with granulocytopenia (37.7%) and 216 patients with agranulocytosis. The resistance rate to imipenem was 3.3%, which was the lowest among the total antimicrobial susceptibilities of 628 Escherichia Coli. The extended-spectrum-beta-lactamase (ESBL)-producing strains accounted for 53.8% among the total patients. The resistance rates of ESBLs-producing-Escherichia coli for the Sulfamethoxazole, Ampicillin, Gentamicin, Cefazolin, Cefuroxime, Cefotaxime, Ceftriaxone, Cefepime, Ceftazidime, Cefoperazone, Piperacillin and Ciprofloxacin were 80.2%, 100.0%, 62.4%, 99.1%, 99.1%, 98.8%, 98.2%, 48.5%, 50.6%, 95.0%, 98.2%, 79.6%, respectively, which were higher than that of non-ESBLs-producing-Escherichia coli (67.9%, 79.7%, 47.6%, 50.0%, 47.2%, 41.0%, 40.3%, 27.2%, 24.1%, 40.0%, 56.2%, 58.3%, respectively), the differences were significant statistically (chi(2)=12.33, 75.90, 13.92, 209.00, 224.94, 259.25, 256.59, 27.79, 46.19, 222.85, 165.08, 33.59, all P<0.05). One hundred and seventy eight patients received venous catheterization when blood culture were performed. All the patients received antimicrobial treatment, mainly including carbapenem antibiotics and beta-lactamase inhibitors combinations. Of which 533 patients were improved, the improvement rate was 84.9%. CONCLUSIONS: There are many risk factors in relation to Escherichia coli bloodstream infection. The antimicrobial resistance rate of ESBLs-producing-Escherichia coli is higher than that of none ESBLs-producing-Escherichia coli. Individualized strategies should be based on antimicrobial sensitivity. PMID- 27266349 TI - [Expression of hypoxia-inducible factor 1alpha in gastric cancer and its clinical signficance]. AB - OBJECTIVE: To explore the expression level and location of hypoxia-inducible factor 1alpha (HIF-1alpha) in gastric cancer (GC) tissues and their relationship with clinicopathological features and clinical outcomes. METHODS: From July to September 2015, 27 pairs of fresh paired GC tissues and adjacent normal tissues were gathered from the Eighth Department of General Surgery of the First Affiliated Hospital of Anhui Medical University. Quantitative real-time PCR (qRT PCR) and Western blot were performed to detect the expression of HIF-1alpha mRNA and protein in these tissues. A total of 191 GC tissues and 46 randomly selected adjacent normal gastric tissues were consecutively collected between December 2006 and September 2008 from Department of General Surgery of the same hospital. Immunohistochemistry were performed on them to detect the expression of HIF 1alpha and CD34[described in terms of microvessel density (MVD)], and correlation of different locations of HIF-1alpha (in cytoplasm or nucleus) with MVD, clinicopathological features, and clinical prognosis was analyzed. RESULTS: The average relative expression level of HIF-1alpha mRNA in GC tissues (0.625+/ 0.170) was significantly higher than in normal adjacent tissues (0.218+/-0.036, t=2.336, P=0.023) by qRT-PCR. From the results of Western blot, the expression level of HIF-1alpha protein increased in GC tissues compared with its corresponding normal tissues. Immunohistochemistry results revealed that positive HIF-1alpha staining was observed in 67.54% GC tissues and 45.65% normal tissues, with significant difference (P=0.006). And 35.08% in GC and 45.65% in normal tissues were cytoplasmic positive (P=0.138); while 37.17% in GC and only 2.17% in normal tissues were nuclear positive, with significant difference (P<0.001). High differentiation group and TNM clinical early stage (I+ II) group had significantly higher cytoplasmic HIF-1alpha expression positive rate compared with low differentiation group (P=0.008) and TNM clinical intermediate-advanced stage (III+ IV) group (P=0.019); whereas low differentiation group had significantly higher nuclear HIF-1alpha expression positive rate compared with high differentiation group (P=0.043). The mean MVD in the nuclear HIF-1alpha positive GC group (115.6 +/- 7.8) was higher than that in the cytoplasmic HIF 1alpha positive GC group (93.1+/-7.5, t=2.077, P=0.040). The median follow-up time was 56(3-81)months. Kaplan-Meier survival analysis and Log-Rank test results showed that nuclear HIF-1alpha positive patients had a shorter survival time (median 45 months) than cytoplasmic HIF-1alpha positive patients (median 64 months, P<0.001). Multivariate Cox regression analysis revealed that differentiation (HR=1.713; 95% CI: 1.019-2.882), depth of invasion (tumor stage, HR=6.137; 95% CI: 1.832-20.556) and lymph node metastasis (HR=2.788; 95% CI: 1.313-5.920) were independent prognostic factors for GC (all P<0.05). CONCLUSION: Different location of HIF-1alpha protein may be realted to the tumorigenesis and progression of GC, and may become a potential prognostic indicator of GC. PMID- 27266350 TI - [Clinical characteristics of bone disease in multiple myeloma and clinical significance of monitoring bone metabolic markers]. AB - OBJECTIVE: To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers. METHODS: The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease. The levels of bone metabolic markers total procollagen type I N-terminal peptide (tPINP) and beta C-terminal telopeptide of type I collagen (beta-CTX) were monitored regularly in the two years following treatment in 66 cases. RESULTS: (1) Among the 178 newly diagnosed MM cases, 167 cases complained of pain in bones on first visit, 35 cases combined with hypercalcemia, 83 cases combined with osteoporosis, 154 cases combined with osteolytic bone destruction, and 73 cases combined with pathologic fracture. The most common osteolytic location was the spine. The most common fracture sites was the spine. (2) According to bone disease grading, the 178 cases were divided into group A (bone grade 0-2, n=51) and group B(bone grade 3-4, n=127). There were no significant differences between group A and group B in gender, median age, therapeutic effect/ineffec, median overall survival, median progress-free survival, mean serum lactic dehydrogenase, mean albumin, urine light chains and serum creatinine(all P>0.05). Compared with group A, group B had lower hemoglobin level[(99.78+/-29.93)vs (108.84+/-29.30) g/L], and higher blood calcium level[(2.47+/-0.40)vs (2.30+/-0.29) mmol/L], serum beta2-microglobuin level[(6.04+/-4.84)vs (4.12+/-3.97)mg/L], and bone marrow plasma cells percentage(33.30%+/-24.87% vs 23.51%+/-22.67%)(all P<0.05). (3) Before treatment, the levels of beta-CTX and tPINP in patients of group B(n=47) were higher than those in group A(n=19)(median 0.78 vs 0.42 MUg/L, 60.95 vs 43.47 MUg/L, both P<0.05). The ratio of beta-CTX /tPINP in group B was higher than that in group A (median 0.017 vs 0.012, P<0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both group A and group B (both P>0.05), the level of beta-CTX decreased significantly compared with that before treatment in both groups(median 0.16 vs 0.42 MUg/L, 0.26 vs 0.78 MUg/L, both P<0.05); the ratio of beta-CTX /tPINP decreased significantly compared with that before treatment in both group A and in group B(median 0.008 vs 0.012, 0.011 vs 0.017, both P<0.05). There were no differences in the level of beta-CTX, tPINP and beta-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that after 3 months in both group A and group B (all P>0.05). (4)All patients were divided into two groups according to the therapeutic effect: effective group included patients who reach the effect of partial remission or better remission(n=48), while ineffective group included patients who did not reach the effect of partial remission(n=18). Before treatment there were no differences in the level of beta-CTX, tPINP and beta CTX/tPINP ratio between the effective groupand the ineffective group (all P>0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both effective group and ineffective group (all P>0.05), but the level of beta-CTX decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.24 vs 0.60 MUg/L, 0.44 vs 0.95 MUg/L, both P<0.05). The ratio of beta CTX /tPINP decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.005 vs 0.012, 0.005 vs 0.011, both P<0.05). There were no differences in the level of beta-CTX, tPINP and beta CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that for 3 months both in effective group and ineffective group (all P>0.05). CONCLUSIONS: Pain in bones, osteolysis and pathological fracture are the most common clinical manifestations in myeloma-related bone disease. The severity of bone disease can reflect the tumor load, but may not affect the therapeutic effect and the overall survival. The bone metabolic markers tPINP and beta-CTX can be used to evaluate the severity of myeloma-related bone disease at diagnosis and to monitor the effect of treatment for bone disease. PMID- 27266351 TI - [Application and effect observation of hybrid aortic stent grafts for endovascular repair in the treatment of complicated infrarenal abdominal aortic aneurysm]. AB - OBJECTIVE: To evaluate the effectiveness of the hybrid graft technique for complicated infrarenal abdominal aortic aneurysms (AAAs). METHODS: The clinical data of 183 patients who underwent endovascular aneurysm repair (EVAR) for AAA with challenging anatomy at Zhongshan Hospital Affiliated to Shanghai Fudan University from 2010 to 2015 were retrospectively analyzed. Endografts were divided into two groups: Hybrid Group (28 cases) used more than one type of stent graft, and Standard Group (110 cases) used only one stent graft type. Patients were recommended to undergo CT angiography at 1, 3, 6, 12 month after the procedure. Clinical data were analyzed with a focus on postoperative hospital stay, endoleak, limb occlusion, complications of approach, complications of system, converted to open operation and secondary intervention. RESULTS: Technical success was achieved in all patients in both groups. Compared with hybrid group and standard group, there was no difference in postoperative hospital stay ((5.35+/-2.99) and (5.92+/-3.70) days, t=0.753, P>0.05). During the follow up, there was no difference in endoleak (10.7% and 18.2%), limb graft occlusion (3.6% and 10.9%), complications of approach (0 and 1.8%), complications of system (7.1% and 0.9%), converted to open operation (0 and 0.9%) between two groups (chi(2)=0.896, 1.408, 0.517, 4.078, 0.256, all P>0.05). However, there was statistically significant difference in secondary intervention between two groups (3.6% and 19.1%, 2=4.011, P<0.05). CONCLUSION: The use of hybrid stent graft in patients with unfavorable neck and iliac artery anatomy AAA is feasible, and it could improve the postoperative outcomes such as secondary intervention rate. PMID- 27266352 TI - [Comparison of clinical features and high-resolution esophageal motility characteristics between esophagogastric junction outflow obstruction and type II achalasia patients]. AB - OBJECTIVES: To compare the clinical features and high-resolution esophageal motility-impedance characteristics among esophagogastric junction outflow obstruction (Eoo) patients, type II achalasia (Ach) patients and healthy controls (Con), in order to explore the values of esophageal high-resolution manometry (HRM) in diagnosis and treatment of Eoo patients. METHODS: Patients with dysphagia were enrolled from December 2011 to December 2014 at the outpatient department of Peking University Third Hospital, so were age-matched healthy volunteers. All the patients with organic obstruction were excluded. All the participants were tested with high-resolution esophageal motility-impedance measurement, the patients were diagnosed as Eoo or Ach according to the Chicago classification criteria. Clinical features and esophageal motility characteristics of Eoo, Ach and Con were analyzed. RESULTS: A total of 23 Eoo, 24 Ach and 20 Con were enrolled, whose gender ratios, average ages and body mass indexes were of no significant differences(all P>0.05). (1) The Eoo group had higher percentage of food reflux[21.7% (5/23) vs 0(0/24), P=0.005]and belching[17.4% (4/23) vs 0 (0/24), P=0.013], but lower percentage of dysphagia[47.8% (11/23) vs 79.2% (19/24), P=0.025]and vomiting[0(0/23) vs 12.5%(3/24), P=0.040]compared with the Ach group, with no significant differences in other symptoms(all P>0.05). Besides, the Eoo group had lower Eckardt scores than the Ach group[1(1, 2) vs 3 (2, 5), P<0.001]. (2) The lower esophageal sphincter (LES) basal pressure-minimum in the Eoo was higher than the Con[(26.73+/-2.77) vs (17.16+/-1.76) mmHg, P<0.05]. The mean LES basal pressure; and the LES integrated relaxation pressure (IRP), IRP-maximum, and LES relaxation percentage were significantly different among Eoo, Ach and Con[(19.80+/-1.25) vs (35.95+/-2.36), (8.43+/-0.72) mmHg, both P<0.05; (23.22+/-2.02) vs (48.37+/ 3.71), (12.32+/-1.29) mmHg, bothP<0.05; 38.61%+/-3.10% vs 12.42%+/-5.66%, 64.00%+/-3.85%, both P<0.05]. (3) There were significant differences in velocity, amplitude, and duration of esophageal peristaltic wave and intrabolus pressure (all P<0.05) among Eoo, Ach and Con; and failed contraction percentage, panesophageal pressurization percentage, premature contraction percentage, and rapid contraction percentage of Eoo were lower than Ach (all P<0.05) while complete contraction percentage of Eoo was high compared with Ach (P<0.001), but no significant differences between Eoo and Con. (4) The Eoo had significantly less incomplete bolus clearance[0.00% (0.00%, 20.00%) vs 100.00% (90.00%, 100.00%), P<0.001]and shorter bolus transit time[(5.44+/-0.29) s vs (24.13+/ 1.69) s, P<0.001]than Ach, but there were no significant differences between Eoo and Con in these two indexes[0.00% (0.00%, 20.00%) vs 0.00% (0.00%, 9.75%); (5.44+/-0.29) s vs (5.30+/-0.19) s; both P>0.05]. CONCLUSIONS: The clinical manifestations and esophageal HRM characteristics of Eoo appear to be between Ach and Con, which suggests that Eoo may be an early-stage of Ach. Further study of the pathophysiological characteristics of Eoo patients may provide more evidence to elucidate the pathogenesis of achalasia. PMID- 27266353 TI - [Clinical analysis of laparoscopic surgery in patients with maintenance hemodialysis and colon cancer]. AB - OBJECTIVE: To explore the safety of laparoscopic assisted radical resection of colon cancer in uremic patients. METHODS: Retrospective analysis of Zhejiang Jinhua Guangfu hospital 2012 March to 2015 March 5 cases of uremia patients complicated with colon cancer underwent laparoscopic assisted colorectal cancer radical resection, and compared with 10 cases, observing two groups of operative time, intraoperative bleeding volume, postoperative drainage volume, lymph nodes dissect, anal exhaust time, postoperative complications, postoperative hospitalization time and postoperative pathological staging. RESULTS: Before operation two groups of age, gender, tumor location was no significant difference (P>0.05). In preoperative comorbidities uremic patients were significantly more than that of ordinary patients, mainly in cardiovascular complications, and patients in the two groups in operation time, intraoperative bleeding, post operative drainage volume, lymph node dissection numbers were no significant difference, the postoperative gastrointestinal function recovery was almost no difference, but postoperative hospitalization time significantly prolonged (P<0.05). CONCLUSIONS: Patients with uremia as long as full preoperative preparation, perioperative management, plus timely hemodialysis, uremia patients undergoing laparoscopic assisted radical surgery is safe and feasible, and it is worth promoting. PMID- 27266354 TI - [Effect of Tripterygium wilfordii polycoride upon inflammation and TLR4/MyD88 signaling pathway in ulcerative colitis rats model]. AB - OBJECTIVE: To observe the effect of Tripterygium wilfordii polycoride (TWP) on ulcerative colitis (UC), and its intervention effect on toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, thus to investigate its possible mechanism. METHODS: Trinitrobenzene sulfonic acid (TNBS)/ethanol enema method was used to set up the UC rat model. With random number table, 90 male Wistar rats were divided into normal control group, model group, TWP low, medium and high dose group (3, 6, 12 mg/kg, respectively) and azathioprine (AZA) group (6 mg/kg), with 15 rates in each group. Four days after enema, rates in each group were given corresponding drug lavage for 14 consecutive days. Disease activity index (DAI), colon gross morphological damage and histological grading of each group were observed. Using Western blot and reverse transcription (RT)-PCR method, the TLR4/MyD88 signaling pathway-related proteins in UC rat intestinal tissue were detected, namely TLR4, MyD88, tumor necrosis factor receptor related factor 6 (TRAF-6), nuclear factor kappa B (NF kappaB), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 beta (IL 1beta). RESULTS: The DAI, colon gross morphological damage, and histological grading of the model group were significantly higher than that of the normal control group (all P<0.01), indicating successful establishment of UC model. The DAI, colon gross morphological damage and histological grading of the TWP high dose group were lower than those of the model group (0.87+/-0.25 vs 1.60+/-0.76, 3.93+/-1.94 vs 5.40+/-2.21, 5.45+/-2.73 vs 13.27+/-3.50, P<0.05). Compared with the normal control group, the mRNA and protein expressions of TLR4, MyD88, TRAF 6, NF-kappaB, TNF-alpha, and IL-1beta in the model group rats were significantly increased (all P<0.01); which were significantly decreased in the TWP high dose group compared with model group rats (mRNA: 2.166+/-0.475 vs 5.647+/-0.275, 1.295+/-0.087 vs 3.774+/-0.418, 1.125+/-0.188 vs 2.535+/-0.320, 1.201+/-0.152 vs 2.082+/-0.077, 1.525+/-0.218 vs 3.094+/-0.022, 1.797+/-0.257 vs 17.152+/-0.145; protein: 0.252+/-0.010 vs 0.277+/-0.008, 0.172+/-0.002 vs 0.213+/-0.005, 0.233+/ 0.006 vs 0.248+/-0.003, 0.099+/-0.003 vs 0.122+/-0.007, 0.238+/-0.002 vs 0.252+/ 0.005, 0.235+/-0.003 vs 0.245+/-0.006, all P<0.05), also decreased in the AZA group (all P<0.01); and there were no significant differences between the TWP high dose group and the AZA group (all P>0.05). CONCLUSIONS: TWP can alleviate intestinal inflammation, promote healing of mucosa, showing a therapeutic effect for UC. One of its mechanisms may be through inhibiting the expression of TLR4, affecting the expression of TRAF-6, which is downstream to MyD66 signaling pathway, thus to suppress the activation of NF-kappaB and reduce the release of inflammatory factor such as TNF-alpha and IL-1beta. PMID- 27266355 TI - [Effects of microRNA-379-5p on proliferation, migration and invasion of hepatocellular carcinoma cell line]. AB - OBJECTIVE: To investigate the effects of microRNA-379-5p (miR-379-5p) on proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells. METHODS: Human HCC cell line HepG2 was infected with lentivirus carrying miR-379 5p (miR-379-5p group) or lentivirus carrying negative control sequences (negative control group). The untreated HepG2 cells represented blank control group. Cell proliferation was determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazoliumbromide (MTT) assays. Cell migration and invasion were assessed by Transwell assays. The mRNA and protein expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 were analyzed by real-time quantitative polymerase chain reaction and Western blot, respectively. RESULTS: Compared with negative control group and blank control group, cell migration and invasion was significantly inhibited in miR-379-5p group (P<0.05). However, there was no significant difference in cell proliferation among the three groups (P>0.05). Furthermore, the mRNA and protein levels of MMP-2 and MMP-9 in miR-379-5p group were significantly lower than that in negative control group and blank control group (P<0.05). CONCLUSION: miR-379-5p can suppress migration and invasion of HCC cell lines, which may be achieved by inhibiting MMP-2 and MMP-9 expressions. PMID- 27266356 TI - [The effect and mechanism of microRNA-21 on cis-dichlorodiamineplatinum resistance in lung cancer cell strain]. AB - OBJECTIVE: To investigate the role of miR-21 on multidrug resistance (MDR) in non small cell lung cancer(NSCLC)and to provide experimental and theoretical basis for MDR reversal. METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to determine the mRNA level of miR-21 both in the chemo-sensitivity cell strain A549 and the chemo-resistance cell strain A549/DDP (primary A549/DDP cells). The miR-21 interference sequence was synthesized and transfected into A549/DDP cells by liposome as the carrier. The miR-21 expression level was knocked down and the change of chemo-sensitivity of cells was detected. Effects of miR-21 on the cell apoptosis and cell cycle in miR-21-depleted A549/DDP cells were analyzed by flow cytometry to elucidate the involvement of miR-21 in MDR reversal in NSCLC. The expression of multidrug-resistant proteins Survivin, Cyclin D1, Epidermal growth factor receptor (EGFR), Multidrug resistance-associated protein1 (MRP1) and Lipoprotein receptor-related protein (LRP) were detected by Western blot. RESULTS: MiR-21 level in multidrug-resistant NSCLC cell line A549/DDP was (5.223+/-0.316) folds higher than that in A549 cell line (t=48.318, P<0.01). Knockdown of miR-21 in A549/DDP cells significantly reversed their sensitivity to cis-DDP, meanwhile, the value of half maximal inhibitory concentration was significantly decreased compared with control group transfected with empty vector ((22.2+/-1.2) and (48.6+/-3.2) MUmol/L, t=5.608, P<0.01). Cell apoptosis rate in A549/DDP cell with knockdown of miR-21 was significantly increased compared with primary A549/DDP cell line ((27.7+/-1.1) % and (16.8+/-1.1) %, t=10.183, P<0.01). Cell cycle G0/G1 phase in A549/DDP cell with knockdown of miR-21 was significantly decreased compared with primary A549/DDP cell line ((37.5+/-1.2) % and (43.4+/-2.3) %, t=8.202, P<0.01). Compared with primary A549/DDP cell line, the expression of Survivin, Cyclin D1, EGFR, MRP1 and LRP in A549/DDP cell with knockdown of miR-21 were significantly decreased ((71.7+/-4.3)%, t=8.325, P<0.01; (69.4+/-4.5)%, t=5.162, P<0.01; (52.3+/-3.2)%, t=8.042, P<0.01; (60.6+/-4.2)%, t=6.641, P<0.01; (72.9+/-3.8)%, t=4.566, P<0.01, respectively). CONCLUSION: miR-21 silencing reverses the multidrug resistance in lung cancer cell via accelerating cell apoptosis and modulating multidrug resistance-related gene expression. miR-21 may be a potential therapeutic candidate in multidrug resistance patients with lung cancer. PMID- 27266357 TI - [The activity of moxalactam against Enterobacteriaceae and anaerobia in vitro]. AB - OBJECTIVE: To observe the antibacterial activity of moxalactam against Enterobacteriaceae bacteria and anaerobic bacteria in vitro, and to compare with other antibacterial drugs, for providing experimental basis for the clinical application of moxalactam. METHODS: Minimum inhibitory concentrations (MICs) of moxalactam and other antibacterial agents against 491 Enterobacteriaceae spp. and anaerobic spp.collecting from clinical settings were determined by agar dilution methods and E-test strips according to the Clinical and Laboratory Standards Institute (CLSI)(2014). RESULTS: Moxalactam showed great antibacterial activity to Enterobacteriaceae spp., including ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp., with the MIC(50), MIC(90), and susceptibility rates of 0.25-4 mg/L, 0.5-8 mg/L, and >90%, respectively. The susceptibility rates of Enterobacteriaceae with ESBLs-producing or non-ESBLs producing to imipenem and meropenem were both higher than 90%. The susceptibility rates of ESBLs-producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.to piperacillin/tazobactam and cefoperazone/sulbactam were 90%, 68%, 53% and 76%, 66%, 76.6%, respectively, while the susceptibility rates of non-ESBLs producing Escherichia coli, Klebsiella pneumoniae, and Proteus spp.were all more than 95%. The susceptibility rates of Enterobacter spp. and other Enterobacter to piperacillin/tazobactam were 80%, 80%and that to cefoperazone/sulbactam were 80%, 76.7%, respectively.The MICs range of moxalactam on anaerobic spp.was from <=0.064 to >256 mg/L, while MIC(50) was 2 mg/L and MIC(90) was 64 mg/L. CONCLUSIONS: Moxalactam showed well activity against ESBLs-producing and non ESBLs-producing Enterobacteriaceae and anaerobia. PMID- 27266358 TI - [Distribution characteristics of serotypes of invasive pneumococcal disease in Chinese mainland children]. AB - OBJECTIVE: To systematically estimate the regional distributions of invasive pneumococcal disease (IPD)'s serotypes in children of Chinese mainland. METHODS: The literatures which described at least 20 strains of streptococcus pneumonia samples isolated from children with IPD in Chinese mainland were included in this study. Finally, 39 literatures met the inclusion criteria and were reviewed in this study. The average frequency of each serotype of streptococcus pneumonia was calculated and the uncertainty of each serotype range was described by 95% CI. RESULTS: This study analyzed a total of 7 391 strains of streptococcus pneumoniae samples which mainly came from north China, east China, central China, south China and southwest regions of China. The results showed that the most common streptococcus pneumonia serotype causing IPD was 19F[30.05% (28.16%-31.98%)], and the second serotype was 23F[12.16% (10.00%-14.28%)], and the others were 19A[9.19% (7.01%-11.37%)], 6B[7.30% (5.09%-9.50%)], 14[7.02% (4.82%-9.23%)], 6A[6.08% (3.87%-8.30%)]and 15B[6.53% (2.88%-7.34%)]. CONCLUSION: The most common streptococcus pneumoniae serotype is 19F, 23F, 19A, 6B, 14, 6A and 15B in Chinese Mainland. PMID- 27266359 TI - Regular cognitive self-monitoring in community-dwelling older adults using an internet-based tool. AB - INTRODUCTION: Monitoring for various health conditions (e.g., breast cancer, hypertension) has become common practice. However, there is still no established tool for regular monitoring of cognition. In this pilot longitudinal study, we examined the utility and feasibility of internet-based cognitive self-monitoring using data from the first 12 months of this ongoing study. METHOD: Cognitively healthy community-dwelling older adults (Montreal Cognitive Assessment >= 26) were enrolled on a rolling basis and were trained in self-administration of the internet-based version of the CogState Brief Battery. The battery uses playing cards and includes Detection, Identification, One Back, and One Card Learning subtasks. RESULTS: Of the 118 participants enrolled, 26 dropped out, mostly around first in-home session. Common reasons for participant attrition were internet browser problems, health problems, and computer problems. Common reasons for delayed session completion were being busy, being out of town, and health problems. Participants needed about one reminder phone call per four completed sessions or one reminder email per five completed sessions. Performance across the monthly sessions showed slight (but significant) improvement on three of the four tasks. Change in performance was unaffected by individual characteristics with the exception of previous computer use, with less frequent users showing greater improvement on One Card Learning. We also found low intraindividual variability in monthly test scores beyond the first self-administered testing session. CONCLUSIONS: Internet-based self-monitoring offers a potentially feasible and effective method of continuous cognitive monitoring among older adults. PMID- 27266360 TI - Erythropoietin may attenuate lung inflammation in a rat model of meconium aspiration syndrome. AB - BACKGROUND: Inflammation is believed to play a key role in the pathophysiology of meconium aspiration syndrome (MAS). PURPOSE OF THE STUDY: The objective was to determine whether the recombinant human Erythropoietin (rhEPO) pretreatment could attenuate meconium-induced inflammation. MATERIALS AND METHODS: In this study, 24 ventilated adult male rats were studied to examine the effects of recombinant human EPO (rhEPO) on meconium-induced inflammation. Seventeen rats were instilled with human meconium (1.5 mL/kg, 65 mg/mL) intratracheally and ventilated for 3 hours. rhEPO (1000 U/kg) (n = 9) or saline (n = 8) was given to the animals. Seven rats that were ventilated and not instilled with meconium served as a sham controlled group. Analysis of the blood gases, interleukin (IL)-1beta, IL-6, IL 8, and tumor necrosis factor (TNF)-alpha in blood and bronchoalveolar lavage (BAL) fluid samples, and lung tissue myeloperoxidase levels were performed. RESULTS: Intrapulmonary instillation of meconium resulted in the increase of TNF alpha (p = 0.005 and p < 0.001, respectively) and IL-8 concentrations (p < 0.001 and p < 0.001, respectively) in BAL fluid in the EPO + meconium and saline + meconium groups compared with the sham-controlled group. rhEPO pretreatment prevented the increase of BAL fluid IL-1beta, IL-6, and IL-8 levels (p < 0.001, p = 0.021, and p = 0.005, respectively), and serum IL-6 levels (p = 0.036). CONCLUSION: rhEPO pretreatment is associated with improved BAL fluid and serum cytokine levels. Pretreatment with rhEPO might reduce the risk of developing of meconium-induced derangements. PMID- 27266361 TI - Effect of Hepatic Perfusion on Microwave Ablation Zones in an Ex Vivo Porcine Liver Model. AB - PURPOSE: To compare the size of ablation zones derived from nonperfused ex vivo livers with ablation zones created using an ex vivo perfused porcine liver model. MATERIALS AND METHODS: Six fresh porcine livers were used to evaluate microwave ablation (MWA). Perfused (n = 3) and nonperfused (n = 3) livers were warmed to 37 degrees C by oxygenated, O-positive human blood reconstituted with Ringer solution, using an organ perfusion circuit. During MWA, perfusion was discontinued in the nonperfused group and maintained in the perfused group. After MWA (140 watts * 2 min at 2.45 GHz) with the Acculis MTA System (AngioDynamics, Latham, New York), ablation zones were bisected sagittally. Sections were stained with nicotinamide adenine dinucleotide (NADH) and hematoxylin-eosin to assess viability of cells in ablation and marginal zones. RESULTS: Comparison of 22 MWA zones (9 in perfused group, 13 in nonperfused group) was performed. Ablation zones demonstrated a central "white" and peripheral "red" zone. Cells in the white zone were nonviable with no NADH staining. The red zone showed progressive NADH staining toward the periphery, suggesting incomplete cell death. White and red zones of the perfused group were significantly smaller compared with the nonperfused group (short axis, 17.8 mm +/- 2.7 vs 21.1 mm +/- 3.2, P = .003; long axis, 40.69 mm +/- 3.9 vs 39.63 mm +/- 5.2, P = .44; intermediate zone,1.33 mm +/ 0.04 vs 2.7 mm +/- 0.14, P < .0001; mean +/- SD). CONCLUSIONS: MWA algorithms provided by this manufacturer are based on nonperfused organ data, which overestimate ablation zone size. Data from perfused liver models may be required for more accurate dosimetry guidelines. PMID- 27266363 TI - Direct Construction of 2-Aryliminochromenes from Arynes, N,S-Keteneacetals, and DMF. AB - A concise and direct synthetic strategy for the construction of 2 aryliminochromene skeleton by cascade three-component coupling reaction of arynes, N,S-keteneacetals, and DMF in good yields has been disclosed. The process demonstrates the first example of aryne chemistry combined with N,S keteneacetals. Using this strategy, an expeditious synthesis of biologically important arylimino-2H-chromene-3- carboxamides was achieved. PMID- 27266362 TI - Angiogenic Response following Radioembolization: Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib. AB - PURPOSE: To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) radioembolization alone vs with sorafenib. MATERIALS AND METHODS: In a single center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization ((90)Y alone, n = 6; (90)Y plus sorafenib, n = 7). RESULTS: In the (90)Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36% vs baseline at 2 weeks and 22% at 4 weeks, and PDGF increased 24% at 2 weeks and 3% at 4 weeks. In the (90)Y/sorafenib arm, Ang 2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49% at 2 weeks and 28% at 4 weeks, and PDGF decreased 31% at 2 weeks and 39% at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. CONCLUSIONS: Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF. PMID- 27266364 TI - Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells. AB - Clinical applications of induced pluripotent stem cells (iPSCs) require development of technologies for the production of "footprint-free" (gene integration-free) iPSCs, which avoid the potential risk of insertional mutagenesis in humans. Previously, several studies have shown that mRNA transfer can generate "footprint-free" iPSCs, but these studies did not use a delivery vehicle and thus repetitive daily transfection was required because of mRNA degradation. Here, we report an mRNA delivery system employing graphene oxide (GO)-polyethylenimine (PEI) complexes for the efficient generation of "footprint free" iPSCs. GO-PEI complexes were found to be very effective for loading mRNA of reprogramming transcription factors and protection from mRNA degradation by RNase. Dynamic suspension cultures of GO-PEI/RNA complexes-treated cells dramatically increased the reprogramming efficiency and successfully generated rat and human iPSCs from adult adipose tissue-derived fibroblasts without repetitive daily transfection. The iPSCs showed all the hallmarks of pluripotent stem cells including expression of pluripotency genes, epigenetic reprogramming, and differentiation into the three germ layers. These results demonstrate that mRNA delivery using GO-PEI-RNA complexes can efficiently generate "footprint free" iPSCs, which may advance the translation of iPSC technology into the clinical settings. PMID- 27266366 TI - Cytotoxic Activity of Oleocanthal Isolated from Virgin Olive Oil on Human Melanoma Cells. AB - Oleocanthal is one of the phenolic compounds of extra virgin olive oil with important anti-inflammatory properties. Although its potential anticancer activity has been reported, only limited evidence has been provided in cutaneous malignant melanoma. The present study is aimed at investigating the selective in vitro antiproliferative activity of oleocanthal against human malignant melanoma cells. Since oleocanthal is not commercially available, it was obtained as a pure standard by direct extraction and purification from extra virgin olive oil. Cell viability experiments carried out by WST-1 assay demonstrated that oleocanthal had a remarkable and selective activity for human melanoma cells versus normal dermal fibroblasts with IC50s in the low micromolar range of concentrations. Such an effect was paralleled by a significant inhibition of ERK1/2 and AKT phosphorylation and downregulation of Bcl-2 expression. These findings may suggest that extra virgin olive oil phenolic extract enriched in oleocanthal deserves further investigation in skin cancer. PMID- 27266367 TI - Action priming with biomechanically possible and impossible grasps: ERP evidence from 6-month-old infants. AB - Coding the direction of others' gestures is a fundamental human ability, since it allows the observer to attend and react to sources of potential interest in the environment. Shifts of attention triggered by action observation have been reported to occur early in infancy. Yet, the neurophysiological underpinnings of such action priming and the properties of gestures that might be crucial for it remain unknown. Here, we addressed these issues by recording electroencephalographic activity (EEG) from 6-month-old infants cued with spatially non-predictive hand grasping toward or away from the position of a target object, i.e., valid and invalid trials, respectively. Half of the infants were cued with a gesture executable by a human hand (possible gesture) and the other half with a gesture impossible to be executed by a human hand. Results show that the amplitude enhancement of the posterior N290 component in response to targets in valid trials, as compared to invalid trials, was present only for infants seeing possible gestures, while it was absent for infants seeing impossible gestures. These findings suggest that infants detect the biomechanical properties of human movements when processing hand gestures, relying on this information to orient their visual attention toward the target object. PMID- 27266365 TI - Indium-based and iodine-based labeling of HPMA copolymer-epirubicin conjugates: Impact of structure on the in vivo fate. AB - Recently, we developed 2nd generation backbone degradable N-(2 hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates which contain enzymatically cleavable sequences (GFLG) in both polymeric backbone and side chains. This design allows using polymeric carriers with molecular weights above renal threshold without impairing their biocompatibility, thereby leading to significant improvement in therapeutic efficacy. For example, 2nd generation HPMA copolymer-epirubicin (EPI) conjugates (2P-EPI) demonstrated complete tumor regression in the treatment of mice bearing ovarian carcinoma. To obtain a better understanding of the in vivo fate of this system, we developed a dual-labeling strategy to simultaneously investigate the pharmacokinetics and biodistribution of the polymer carrier and drug EPI. First, we synthesized two different types of dual-radiolabeled conjugates, including 1) (111)In-2P-EPI-(125)I (polymeric carrier 2P was radiolabeled with (111)In and drug EPI with (125)I), and 2) (125)I 2P-EPI-(111)In (polymeric carrier 2P was radiolabeled with (125)I and drug EPI with (111)In). Then, we compared the pharmacokinetics and biodistribution of these two dual-labeled conjugates in female nude mice bearing A2780 human ovarian carcinoma. There was no significant difference in the blood circulation between polymeric carrier and payload; the carriers ((111)In-2P and (125)I-2P) showed similar retention of radioactivity in both tumor and major organs except kidney. However, compared to (111)In-labeled payload EPI, (125)I-labeled EPI showed lower radioactivity in normal organs and tumor at 48h and 144h after intravenous administration of conjugates. This may be due to different drug release rates resulting from steric hindrance to the formation of enzyme-substrate complex as indicated by cleavage experiments with lysosomal enzymes (Tritosomes). A slower release rate of EPI(DTPA)(111)In than EPI(Tyr)(125)I was observed. It may be also due to in vivo catabolism and subsequent iodine loss as literature reported. Nevertheless, tumor-to-tissue uptake ratios of both radionuclides were comparable, indicating that drug-labeling strategy does not affect the tumor targeting ability of HPMA copolymer conjugates. PMID- 27266368 TI - Graphene-Silver-Induced Self-Polarized PVDF-Based Flexible Plasmonic Nanogenerator Toward the Realization for New Class of Self Powered Optical Sensor. AB - Plasmonic characteristics of graphene-silver (GAg) nanocomposite coupled with piezoelectric property of Poly(vinylidene fluoride) (PVDF) have been utilized to realize a new class of self-powered flexible plasmonic nanogenerator (PNG). A few layer graphene has been prepared in a facile and cost-effective method and GAg doped PVDF hybrid nanocomposite (PVGAg) is synthesized in a one-pot method. The PNG exhibits superior piezoelectric energy conversion efficiency (~15%) under the dark condition. The plasmonic behavior of GAg nanocomposite makes the PNG highly responsive to the visible light illumination that leads to ~50% change in piezo voltage and ~70% change in piezo-current, leading to enhanced energy conversion efficiency up to ~46.6%. The piezoelectric throughput of PNG (e.g., capacitor charging performance) has been monitored during the detection of the different wavelengths of visible light illumination and showed maximum selectivity to the green light. The simultaneous mechanical energy harvesting and visible-light detection capabilities of the PNG are attractive for futuristic self-powered optoelectronic smart sensors and devices. PMID- 27266369 TI - Role of individual-housing-based socioeconomic status measure in relation to smoking status among late adolescents with asthma. AB - PURPOSE: We aimed to assess whether smoking status among individuals in late adolescence (19-22 years) with asthma was associated with socioeconomic status (SES) defined by HOUSES, an individual-housing-based SES measure. METHODS: A population-based cross-sectional study was conducted among the 1988-1989 Olmsted County, Minnesota Birth Cohort, with physician-diagnosed asthma and that lived in the community during the study period (November 1, 2008-October 31, 2012). Using a z score for housing value, actual square footage, and numbers of bedrooms and bathrooms, HOUSES was formulated and categorized into quartiles. Smoking status (both current and past smoker) was compared among subjects with different SES as measured by HOUSES using logistic regression, adjusting for age and sex. RESULTS: Among 289 eligible subjects, 287 (99%) were successfully geo-coded to real property data for HOUSES. Of the 257 subjects whose smoke exposure was recorded, 70 (27%) had a history of smoking (either past or current). An inverse association was observed between HOUSES and smoking status after accounting for age, gender, and General Medical Examination status (adjusted OR = 0.39, 95% CI = 0.18-0.87 for comparing highest vs. lowest HOUSES in quartile; overall P = .02). CONCLUSIONS: A significant proportion of individuals with asthma in late adolescence was smokers during the study period, disproportionally affecting those with lower SES. PMID- 27266370 TI - Contemporary surgical issues in paediatric cochlear implantation. AB - OBJECTIVE: To review the contemporary surgical issues in paediatric cochlear implantation (CI) based on published evidence. DESIGN: Narrative literature review. RESULTS: Surgical challenges in paediatric CI are discussed, with respect to post meningitic labyrinthitis ossificans; cochlear malformation; cochlear implantation in infants; auditory neuropathy and cochlear nerve deficiency; bilateral cochlear implantation; hearing preservation; otitis media; and device failure. CONCLUSION: Early CI is recommended if bacterial meningitis causes profound sensorineural hearing loss (SNHL). CI in cochleovestibular malformation requires pre-operative imaging to plan surgical technique, choice of electrode, and to anticipate complication. Children with congenital severe to profound SNHL should undergo early bilateral simultaneous implantation, preferably before 12 months of age, except those with auditory neuropathy spectrum disorder who should be implanted after one year. Soft surgical technique should be deployed in an attempt to preserve any residual hearing. Otitis media with effusion is not a contraindication to cochlear implantation, but active or recurrent acute otitis media requires resolution of infection with grommet insertion pre-operatively. Device failure in CI recipients requires a stepwise audiological, medical, radiological, and device integrity assessment to determine the need for reimplantation. PMID- 27266371 TI - Endothelin-Receptor Antagonists beyond Pulmonary Arterial Hypertension: Cancer and Fibrosis. AB - The endothelin axis and in particular the two endothelin receptors, ETA and ETB, are targets for therapeutic intervention in human diseases. Endothelin-receptor antagonists are in clinical use to treat pulmonary arterial hypertension and have been under clinical investigation for the treatment of several other diseases, such as systemic hypertension, cancer, vasospasm, and fibrogenic diseases. In this Perspective, we review the molecules that have been evaluated in human clinical trials for the treatment of pulmonary arterial hypertension, as well as other cardiovascular diseases, cancer, and fibrosis. We will also discuss the therapeutic consequences of receptor selectivity with regard to ETA-selective, ETB-selective, or dual ETA/ETB antagonists. We will also consider which chemical characteristics are relevant to clinical use and the properties of molecules necessary for efficacy in treating diseases against which known molecules displayed suboptimal efficacy. PMID- 27266372 TI - Bagging survival tree procedure for variable selection and prediction in the presence of nonsusceptible patients. AB - BACKGROUND: For clinical genomic studies with high-dimensional datasets, tree based ensemble methods offer a powerful solution for variable selection and prediction taking into account the complex interrelationships between explanatory variables. One of the key component of the tree-building process is the splitting criterion. For survival data, the classical splitting criterion is the Logrank statistic. However, the presence of a fraction of nonsusceptible patients in the studied population advocates for considering a criterion tailored to this peculiar situation. RESULTS: We propose a bagging survival tree procedure for variable selection and prediction where the survival tree-building process relies on a splitting criterion that explicitly focuses on time-to-event survival distribution among susceptible patients. A simulation study shows that our method achieves good performance for the variable selection and prediction. Different criteria for evaluating the importance of the explanatory variables and the prediction performance are reported. Our procedure is illustrated on a genomic dataset with gene expression measurements from early breast cancer patients. CONCLUSIONS: In the presence of nonsusceptible patients among the studied population, our procedure represents an efficient way to select event-related explanatory covariates with potential higher-order interaction and identify homogeneous groups of susceptible patients. PMID- 27266373 TI - Iterative reconstruction can permit the use of lower X-ray tube current in CT coronary artery calcium scoring. AB - OBJECTIVE: CT coronary artery calcium scoring (CACS) is additive to traditional risk factors for predicting future cardiac events but is associated with relatively high radiation doses. We assessed the feasibility of CACS radiation dose reduction using a lower tube current and iterative reconstruction (IR). METHODS: Artificial noise was added to the raw data from 27 CACS studies from patients who were symptomatic to simulate lower tube current scanning (75, 50 and 25% original current). All studies were performed on the same CT scanner at 120 kVp. Data were reconstructed using filtered back projection [Quantum Denoising Software (QDS+)] and IR [adaptive iterative dose reduction three dimensional mild, standard and strong]. Agatston scores were independently measured by two readers. CACS percentile risk scores were calculated. RESULTS: At 75, 50 and 25% tube currents, all adaptive iterative dose reduction (AIDR) reconstructions decreased image noise relative to QDS+ (p < 0.05). All AIDR reconstructions resulted in small reductions in Agatston score relative to QDS+ at the standard tube current (p < 0.05). Agatston scores increased with QDS+ at 75, 50 and 25% tube current (p < 0.05), whereas no significant change was observed with AIDR mild at any tested tube current. No difference in the percentile risk score with AIDR mild at any tube current occurred compared with QDS+ at standard tube current (p > 0.05). Interobserver agreement for AIDR mild remained excellent even at 25% tube current (intraclass correlation coefficient 0.997). CONCLUSION: Up to 75% reduction in CACS tube current is feasible using AIDR mild. ADVANCES IN KNOWLEDGE: AIDR mild IR permits low tube current CACS whilst maintaining excellent intraobserver and interobserver variability and without altering risk classification. PMID- 27266374 TI - The impact of greyscale inversion for nodule detection in an anthropomorphic chest phantom: a free-response observer study. AB - OBJECTIVE: The aim of this work was to assess the impact of greyscale inversion on nodule detection on posteroanterior chest X-ray images. Previous work has attempted this, with no consensus opinion formed. We assessed the value of "fast flicking" between standard and inverted display modes for nodule detection. METHODS: Six consultant radiologists (with 5-32 years' reporting experience) completed an observer task under the free-response paradigm. An anthropomorphic chest phantom was loaded with 50 different configurations of simulated nodules (1 4 nodules per case) measuring 5, 8, 10 and 12 mm in spherical diameter; each configuration represented a single case. In addition, 25 cases contained no nodules. Images were displayed in three modes: (i) standard, (ii) inverted and (iii) fast-flicking between standard and inverted display modes. Each observer completed the study in a different order of display (i, ii, iii) using a calibrated 5-megapixel monitor. Nodules were localized with mouse clicks and ratings assigned using a 1-10 discrete slider-bar confidence scale. Rjafroc (Pittsburgh, PA) was used for data analysis; differences in nodule detection performance were considered significant at 0.05. RESULTS: The observer-averaged weighted jackknife alternative free-response receiver-operating characteristic figures of merit were 0.715 (standard), 0.684 (inverted) and 0.717 (fast flicking). Random-reader fixed-case analysis revealed no statistically significant difference between any treatment pair [F(2,8) = 1.22; p = 0.345]. CONCLUSION: No statistically significant difference in nodule detection was found for the three display conditions. ADVANCES IN KNOWLEDGE: We have investigated the impact of fast-flicking between standard and inverted display modes for the detection of nodules. We found no benefit. PMID- 27266384 TI - Application of near infrared spectroscopy (NIR), X-ray fluorescence (XRF) and chemometrics to the differentiation of marmora samples from the Mediterranean basin. AB - Near-infrared (NIR) and X-ray fluorescence spectra were recorded for 15 different samples of marmora, from the Mediterranean Basin and of different colours. After appropriate pretreatment (SNV transform + second derivative), the results were subjected to principal component analysis (PCA) treatment with a view to differentiating them. The observed differences among the samples were chemically interpreted by highlighting the NIR wavelengths and minerals, respectively, contributing the most to the PCA models. Moreover, a mid-level data fusion protocol allowed integrating the information from the different techniques and, in particular, to correctly identify (based on the distance in the score space) three test samples of known type. Moreover, it should be stressed that positive results on the differentiation and identification of marmora were obtained using two completely non-invasive, non-destructive and relatively inexpensive techniques, which can also be used in situ. PMID- 27266383 TI - Quantitative Structure-Retention Relationship Models To Support Nontarget High Resolution Mass Spectrometric Screening of Emerging Contaminants in Environmental Samples. PMID- 27266385 TI - (99m)Tc-Methoxy-Isobutyl-Isonitrile Scintigraphy Is a Useful Tool for Assessing the Risk of Malignancy in Thyroid Nodules with Indeterminate Fine-Needle Cytology. AB - BACKGROUND: Thyroid nodular disease is a very common clinical problem. The diagnostic algorithm includes laboratory tests, thyroid ultrasound (US), thyroid scintigraphy, and, if necessary, US-guided fine-needle aspiration cytology. However, cytology results are reported as indeterminate in a not negligible number of patients. This is a central problem in the workup of patients, since about 55-85% of those undergoing surgery do not have thyroid cancer at final histology diagnosis. The aim of this study was to evaluate prospectively the role of (99m)Tc-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) thyroid scintigraphy in differentiating malignant from benign thyroid nodules with indeterminate cytology using quantitative analysis. METHOD: One hundred five patients affected by nodular thyroid goiter and with a euthyroid or hypothyroid functional status were prospectively evaluated. All patients had a suspicious nodule >=15 mm in maximal diameter on US. All nodules were "cold" on (99m)Tc-pertechnetate scintigraphy and had a cytological diagnosis of class III or IV according to the Bethesda system. Planar images of the thyroid were acquired 10 and 60 minutes after (99m)Tc-MIBI administration. All cold nodules were MIBI-positive. Using quantitative analysis, the MIBI washout index (WOind) was calculated as a percentage reduction value of mean MIBI nodular uptake between early (+10 minutes) and late (+60 minutes) scans. RESULTS: Subdividing the patients into positive and negative for malignancy (either including or excluding patients with Hurthle cell adenoma) and performing receiver operating characterist curve analysis, the optimal WOind cutoff in differentiating malignant from benign follicular lesions was set at 19%. The overall sensitivity and specificity of (99m)Tc-MIBI quantitative analysis in identifying patients with malignant lesions was 100% and 90.9%, respectively. However, after excluding patients with Hurthle cell adenomas from the negative patient group, the overall sensitivity and specificity both reached 100%. CONCLUSION: The use of MIBI scintigraphy using quantitative analysis in the workup of cold nodules with indeterminate cytology is suggested in order to stratify patient risk for a malignant lesion better, thus reducing the number of patients referred to surgery. Surgical treatment should be planned in those patients with a WOind up to -19%. PMID- 27266386 TI - Open vs. closed reduction combined with minimally invasive plate osteosynthesis in humeral fractures. AB - Aim To explore a more effective surgical procedure, the outcomes of closed manipulative reduction (CMR) combined with minimally invasive plate osteosynthesis (MIPO) and conventional open reduction and internal fixation (ORIF) for treating proximal humeral fractures were compared. Material and methods In a retrospective study of patients operated for humerus shaft fractures from April 2008 to July 2011, the outcomes of 33 patients treated with CMR/MIPO were compared with the outcomes of 42 patients treated with ORIF. The fractures were classified, and the incision length, blood transfusion, operating time, as well as the VAS (Visual Analog Scale) pain scores were analyzed. The neck-shaft angles of the proximal humerus were detected, and the postoperative function of the shoulder was evaluated. Results The mean values of incision length, blood transfusion, and VAS pain scores at the 1st and 3rd day after CMR/MIPO and operation time were lower than that of ORIF. The postoperative radiographs verified good position of all screws and satisfactory bone fracture reduction in both groups. Meanwhile, in the ORIF group, nonunion (three cases) and humeral head necrosis (four cases) were detected. Conclusions The MR/MIPO technique showed smaller incisions, easier operation, less blood transfusion and more effective recovery of shoulder joint function for treating proximal humeral fractures than ORIF. PMID- 27266387 TI - Nuclear translocation of the cardiac L-type calcium channel C-terminus is regulated by sex and 17beta-estradiol. AB - The cardiac voltage gated l-type Ca(2+) channel (Cav1.2) constitutes the main entrance gate for Ca(2+) that triggers cardiac contraction. Several studies showed that the distal C-terminus fragment of Cav1.2 alpha1C subunit (alpha1C dCT) is proteolytically cleaved and shuttles between the plasma membrane and the nucleus, which is regulated both developmentally and by Ca(2+). However, the effects of sex and sex hormone 17beta-estradiol (E2, estrogen) on alpha1C-dCT nuclear translocation are still unexplored. To investigate the sexual disparity in the alpha1C-dCT nuclear translocation, we first generated an antibody directed against a synthetic peptide (GRRASFHLE) located in alpha1C-dCT, and used it to probe ventricular myocytes from adult female and male mice. Immunocytochemistry of isolated mouse primary adult ventricular myocytes revealed both nuclear staining and cytosolic punctuate staining around the T-tubules. The ratio of nuclear to cytosolic intensity (Inuc/Icyt) was significantly higher in isolated female cardiomyocytes (1.42+/-0.05) compared to male cardiomyocytes (1.05+/ 0.02). Western blot analysis of nuclear fraction confirmed these data. Furthermore, we found a significant decrease in nuclear staining intensity of alpha1C-dCT in both female and male cardiomyocytes upon serum withdrawal for 18h (Inuc/Icyt 1.05+/-0.02 and 0.89+/-0.02, respectively). Interestingly, subsequent E2 treatment (10(-8)M) for 8h normalized the intracellular distribution of alpha1C-dCT in male cardiomyocytes (Inuc/Icyt 1.04+/-0.02), but not in female cardiomyocytes. Acute treatment of male cardiomyocytes with E2 for 45min revealed a similar effect. This effect of E2 was revised by ICI indicating the involvement of ER in this signaling pathway. Taken together, our results showed that the shuttling of alpha1C-CT in cardiomyocytes is regulated in a sex-dependent manner, and E2-activated ER may play a role in the nuclear shuttling of alpha1C-dCT in male cardiomyocytes. This may explain, at least partly, the observed sex differences in the regulation of cardiac Cav1.2 channel activity. PMID- 27266388 TI - A series of robust genetic indicators for definitive identification of cardiomyocytes. AB - Definitively identifying the cell type of newly generated cells in the heart and defining their origins are central questions in cardiac regenerative medicine. Currently, it is challenging to ascertain the myocardial identity and to track myocardial progeny during heart development and disease due to lack of proper genetic tools. This may lead to many misinterpretations of the findings in cardiac regenerative biology. In this study, we developed a set of novel mouse models by inserting double reporter genes nlacZ/H2B-GFP, mGFP/H2B-mCherry into the start codon of Tnnt2 and Myh6. nlacZ (nuclear lacZ) and mGFP (membrane GFP) are flanked by two LoxP sites in these animals. We found that the reporter genes faithfully recapitulated Tnnt2 and Myh6 cardiac expression from embryonic stage and adulthood. The reporter mice provide unprecedented robustness and fidelity for visualizing and tracing cardiomyocytes with nuclear or cell membrane localization signals. These animal models offer superior genetic tools to meet a critical need in studies of heart development, cardiac stem cell biology and cardiac regenerative medicine. PMID- 27266389 TI - Interaction between platelets and endothelial progenitor cells via LPA-Edg-2 axis is augmented by PPAR-delta activation. AB - BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-delta is a nuclear receptor regulating cell metabolism. The role of PPAR-delta in late endothelial progenitor cells (EPCs) has not been fully elucidated. We aim to understand the effects of PPAR-delta activation on late EPC and to reveal the underlying mechanism. METHODS AND RESULTS: Treatment with a highly selective PPAR-delta agonist (GW501516) induced proliferation of late EPCs and enhanced their vasculogenic potential. Search for the target molecule of PPAR-delta activation revealed endothelial differentiation gene (Edg)-2. Chromatin immunoprecipitation and promoter assays demonstrated that Edg-2 gene was specifically induced by PPAR delta through direct transcriptional activation. Lysophosphatidic acid (LPA), an Edg ligand, mimicked the pro-vasculogenic effects of GW501516 in late EPCs whereas Edg antagonist (Ki16425) blocked these effects. Edg-2 is a membrane receptor for LPA which is a major growth factor from activated platelets. Thus, the interaction between platelets and late EPCs via the LPA-Edg-2 axis was assessed. Platelet supernatant boosted the pro-vasculogenic effects of GW501516, which was reversed by antagonist to PPAR-delta (GSK0660) or Edg (Ki16425). Both of in vivo Matrigel plug model and mouse skin punch-wound model demonstrated that the combination of platelets and PPAR-delta-activated late EPCs synergistically enhanced vascular regeneration. CONCLUSIONS: There exists a synergistic interaction between human platelets and late EPCs leading to vascular regeneration. This interaction consists of LPA from platelets and its receptor Edg-2 on the surface of EPCs and can be potentiated by PPAR-delta activation in EPCs. A PPAR-delta agonist is a good candidate to achieve vasculogenesis for ischemic vascular disease. PMID- 27266391 TI - Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation. AB - The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring. PMID- 27266390 TI - Therapeutic monoclonal antibodies for respiratory diseases: Current challenges and perspectives, March 31 - April 1, 2016, Tours, France. AB - Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence "MAbImprove," the GDR 3260 "Antibodies and therapeutic targeting," and the Grant Research program ARD2020 "Biotherapeutics" invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 April 1, 2016 in Tours, France. PMID- 27266392 TI - Brief commentary for brain, behavior, and immunity. PMID- 27266393 TI - The effect of time to sentinel lymph node biopsy on cutaneous melanoma survival. AB - BACKGROUND: Whether timing of sentinel lymph node biopsy (SLNB) in cutaneous melanoma improves survival is not yet clear. The aim of this study was to investigate if the timing of SLNB influences long-term melanoma mortality. METHODS: A 10-year retrospective cohort study was conducted on 748 cutaneous melanoma patients who underwent excision of the SLN. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models. RESULTS: After adjusting for sex, age, Breslow thickness, mitotic rate, ulceration, and histologic type, patients who underwent early SLNB (<=30 days) and resulted positive on final pathology had a 3 times decreased risk of melanoma mortality (hazard ratio = .29; 95%confidence interval = .11 to .77) in comparison to patients who underwent delayed SLNB (>=31 days) and resulted positive on final pathology. CONCLUSIONS: Our findings suggest that early SLNB (<=30 days) improves melanoma survival. PMID- 27266394 TI - Prior probabilities modulate cortical surprise responses: A study of event related potentials. AB - The human brain predicts events in its environment based on expectations, and unexpected events are surprising. When probabilistic contingencies in the environment are precisely instructed, the individual can form expectations based on quantitative probabilistic information ('inference-based learning'). In contrast, when probabilistic contingencies are imprecisely instructed, expectations are formed based on the individual's cumulative experience ('experience-based learning'). Here, we used the urn-ball paradigm to investigate how variations in prior probabilities and in the precision of information about these priors modulate choice behavior and event-related potential (ERP) correlates of surprise. In the urn-ball paradigm, participants are repeatedly forced to infer hidden states responsible for generating observable events, given small samples of factual observations. We manipulated prior probabilities of the states, and we rendered the priors calculable or incalculable, respectively. The analysis of choice behavior revealed that the tendency to consider prior probabilities when making decisions about hidden states was stronger when prior probabilities were calculable, at least in some of our participants. Surprise related P3b amplitudes were observed in both the calculable and the incalculable prior probability condition. In contrast, calculability of prior probabilities modulated anteriorly distributed ERP amplitudes: when prior probabilities were calculable, surprising events elicited enhanced P3a amplitudes. However, when prior probabilities were incalculable, surprise was associated with enhanced N2 amplitudes. Furthermore, interindividual variability in reliance on prior probabilities was associated with attenuated P3b surprise responses under calculable in comparison to incalculable prior probabilities. Our results suggest two distinct neural systems for probabilistic learning that are recruited depending on contextual cues such as the precision of probabilistic information. Individuals with stronger tendencies to rely on calculable prior probabilities seem to have better adapted expectations at their disposal, as indicated by an attenuation of their P3b surprise responses when prior probabilities are calculable. PMID- 27266396 TI - Why are children sedentary: an examination using the International Study of Childhood Obesity, Lifestyle and the Environment. AB - Physical inactivity and sedentary behaviour have been independently associated with a wide range of negative health indicators including obesity, poor cardio metabolic health, and poor psychosocial health. The overarching objective of this research was to gain a better understanding as to why children are sedentary and where we need to focus public health messages and interventions to reduce sedentary behaviour. Specifically, I aimed to provide insight on current awareness of sedentary behaviour guidelines, determine important correlates of total sedentary time (SED) and screen time (ST) in Canadian children, and understand correlates of SED and ST in a global context. The primary dataset used for this project was the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE). Background work was completed to review current literature on knowledge and awareness of Canadian physical activity and sedentary behaviour guidelines (in all age groups) and to understand the representativeness of the ISCOLE dataset. In addition to the 2 background papers, this dissertation includes 3 manuscripts, all prepared for submission in scientific, peer-reviewed journals: Canadian physical activity and screen time guidelines: do children know?, Correlates of objectively measured sedentary time and self-reported screen time in Canadian children, and Correlates of total sedentary time and screen time in 9-11 year-old children around the world: The International Study of Childhood Obesity, Lifestyle and the Environment. Overall, this work showed the majority of children around the world are accumulating large amounts of sedentary time, and exceeded current screen time guidelines. We found that the large majority of Canadian children are not aware of screen time guidelines; however, a greater proportion of children could identify physical activity guidelines. We also identified a number of correlates of SED and ST in Canadian children and in children around the world. The most common correlates included weight status and access to electronics in the house. Taken together, this work suggests that public health messaging should focus on increasing awareness of screen time guidelines. While increasing awareness of the guidelines, messaging can be tailored to promoting healthy weight status and reducing (or removing) children's access to electronic devices in hopes of reducing overall time spent sedentary. PMID- 27266395 TI - EEG and behavioural correlates of different forms of motor imagery during action observation in rhythmical actions. AB - Recent studies show that participants can engage in motor imagery (MI) and action observation (AO) simultaneously (AO+MI), indicating a capacity for dual action simulation. Here we studied the electrophysiological correlates and behavioural outcomes of two forms of AO+MI, along with pure MI and pure AO control conditions. In synchronised AO+MI, participants imagined performing a rhythmical action in synchrony with an observed distractor action. In contrast in static AO+MI, where the imagery served to conflict with AO, participants imagined holding a static hand posture during AO. Following synchronised AO+MI, rhythmical execution was strongly biased toward the cycle time of the previously observed rhythm ('imitation bias'), whereas a weaker bias was found following pure MI, and particularly for static AO+MI. In line with these findings, event-related desynchronisation (ERD) in primary sensorimotor and parietal regions was more pronounced in synchronised AO+MI compared to both pure AO and pure MI. These ERD amplitudes were, however, highly similar for static and synchronised AO+MI; suggesting that, regardless of co-represented content, both AO+MI states produced stronger motor activations than single action simulation. In contrast, synchronised AO+MI produced significantly stronger ERD in rostral prefrontal cortex compared to the other three conditions. This specific rostral prefrontal involvement most likely reflected additional cognitive processing for aligning dual action simulations. Together these results provide an important empirical validation of different AO+MI states, in that the imitation bias was strongly modulated by the content of the AO+MI instructions, and that synchronised AO+MI produced stronger behavioural and neurophysiological effects compared to pure AO or MI. PMID- 27266400 TI - Prevalence and Correlates of Sex Exchange Among a Nationally Representative Sample of Adolescents and Young Adults. AB - The present study examines prevalence and correlates of exchanging sex for drugs, money, food shelter, or other favors (sex exchange) among a nationally representative sample of youth and young adults. Adolescents and young adults (n = 11,620, 53% female, 47% male) from the National Longitudinal Study of Adolescent Health were used for the current sample. Participants completed in home interviews at both waves. Results revealed that sex exchange was reported by 4.9% (n = 569) of the population in wave 2 or wave 3, and 4.6% (n = 26) of those who exchanged sex did so at both waves. More males reported exchanging sex than females (n = 332 versus n = 237). Respondents who reported child sexual abuse were more likely to exchange sex (95% CI 2.51-4.28, p < .05) than respondents who reported any other form of child abuse. Both males and females who engaged in sex exchange were at greater risk for sexually transmitted infections; however, the odds of ever exchanging sex were highest among males who ever had gonorrhea (OR = 6.2; 95% CI 3.75-10.3). Although sex exchange has been studied extensively among homeless and runaway youth, the current study reveals sex exchange also occurs in the general population. PMID- 27266401 TI - Incorporating pharmacodynamic considerations into caffeine therapeutic drug monitoring in preterm neonates. AB - BACKGROUND: This study sought to assess the pharmacokinetic and pharmacodynamic relationships of caffeine citrate therapy in preterm neonates who had therapeutic drug monitoring (TDM) in the post-extubation period. METHODS: A retrospective observational study was conducted in preterm neonates who received caffeine citrate therapy for apnea of prematurity and had TDM done in the post-extubation period between January 2006 and October 2011. The relationships between pharmacodynamic effects (heart rate, respiratory rate, episodes of apnea, adverse events) and caffeine serum concentrations were explored. RESULTS: A total of 177 blood samples were obtained from 115 preterm neonates with a median (range) gestational age of 29 (24 - 33) weeks and birth weight of 1230 (607 - 2304) kg. Caffeine citrate therapy was initiated at a median (interquartile range) postnatal age of 1 (1 - 3) day and TDM was performed at a postnatal age of 15 (10 - 24) days. No direct correlations were found between respiratory rate or apneic episodes and caffeine serum concentrations; however, heart rate and caffeine serum concentrations were significantly correlated (p < 0.05). Dosing regimen of 40/5 mg/kg q12h (loading dose/maintenance dose, time interval) led to similar endotracheal re-intubation rate but increased percentage of patients experiencing tachycardia compared to the standard regimen of 20/5 mg/kg q24h (44.7 % vs 10.2 %, p < 0.001). CONCLUSION: Based on this retrospective study, no correlation between episodes of apnea and caffeine serum concentrations was found in neonates who had TDM of caffeine citrate therapy in the post-extubation period, whereas a significant association between tachycardia and concentrations existed. Notwithstanding the absence of severe adverse reactions, TDM should be considered in critically ill neonates with unexplained adverse effects, such as tachycardia. PMID- 27266402 TI - Novel MEKC method for determination of sodium 2-mercaptoethanesulfonate in human plasma with in-capillary derivatization and UV detection. AB - Sensitive electrophoretic method for determination of total sodium 2 mercaptoethanesulfonate (mesna) in human plasma, based on the stacking with high salt concentration in MEKC and in-capillary derivatization with 2-chloro-1 methyllepidinium tetrafluoroborate followed by UV detection was developed. In the method 0.03molL(-1)pH 7 phosphate buffer with the addition of 0.01molL(-1) SDS, and 10% ACN was used as a BGE. The limit of quantification (LOQ) of the method was 0.5MUmolL(-1). Linearity in detector response was observed over the range of 0.5-10MUmolL(-1) with the correlation coefficient 0.9971. The intra- and inter day accuracy (three concentration levels, 5 days, n=3) of the method ranged from 97.2 to 110.0% and from 94.0 to 101.2%, respectively. The novel MEKC method with UV detection proved to be suitable for determination of total mesna in human plasma. PMID- 27266403 TI - A Comparative Study on Graphene Oxide and Carbon Nanotube Reinforcement of PMMA Siloxane-Silica Anticorrosive Coatings. AB - Carbon nanotubes (CNTs) and graphene oxide (GO) have been used to reinforce PMMA siloxane-silica nanocomposites considered to be promising candidates for environmentally compliant anticorrosive coatings. The organic-inorganic hybrids were prepared by benzoyl peroxide (BPO)-induced polymerization of methyl methacrylate (MMA) covalently bonded through 3-(trimethoxysilyl)propyl methacrylate (MPTS) to silica domains formed by hydrolytic condensation of tetraethoxysilane (TEOS). Single-walled carbon nanotubes and graphene oxide nanosheets were dispersed by surfactant addition and in a water/ethanol solution, respectively. These were added to PMMA-siloxane-silica hybrids at a carbon (CNT or GO) to silicon (TEOS and MPTS) molar ratio of 0.05% in two different matrices, both prepared at BPO/MMA molar ratios of 0.01 and 0.05. Atomic force microscopy and scanning electron microscopy showed very smooth, homogeneous, and defect-free surfaces of approximately 3-7 MUm thick coatings deposited onto A1020 carbon steel by dip coating. Mechanical testing and thermogravimetric analysis confirmed that both additives CNT and GO improved the scratch resistance, adhesion, wear resistance, and thermal stability of PMMA-siloxane-silica coatings. Results of electrochemical impedance spectroscopy in 3.5% NaCl solution, discussed in terms of equivalent circuits, showed that the reinforced hybrid coatings act as a very efficient anticorrosive barrier with an impedance modulus up to 1 GOmega cm(2), approximately 5 orders of magnitude higher than that of bare carbon steel. In the case of GO addition, the high corrosion resistance was maintained for more than 6 months in saline medium. These results suggest that both carbon nanostructures can be used as structural reinforcement agents, improving the thermal and mechanical resistance of high performance anticorrosive PMMA-siloxane-silica coatings and thus extending their application range to abrasive environments. PMID- 27266404 TI - Regulators of gene expression in Enteric Neural Crest Cells are putative Hirschsprung disease genes. AB - The enteric nervous system (ENS) is required for peristalsis of the gut and is derived from Enteric Neural Crest Cells (ENCCs). During ENS development, the RET receptor tyrosine kinase plays a critical role in the proliferation and survival of ENCCs, their migration along the developing gut, and differentiation into enteric neurons. Mutations in RET and its ligand GDNF cause Hirschsprung disease (HSCR), a complex genetic disorder in which ENCCs fail to colonize variable lengths of the distal bowel. To identify key regulators of ENCCs and the pathways underlying RET signaling, gene expression profiles of untreated and GDNF-treated ENCCs from E14.5 mouse embryos were generated. ENCCs express genes that are involved in both early and late neuronal development, whereas GDNF treatment induced neuronal maturation. Predicted regulators of gene expression in ENCCs include the known HSCR genes Ret and Sox10, as well as Bdnf, App and Mapk10. The regulatory overlap and functional interactions between these genes were used to construct a regulatory network that is underlying ENS development and connects to known HSCR genes. In addition, the adenosine receptor A2a (Adora2a) and neuropeptide Y receptor Y2 (Npy2r) were identified as possible regulators of terminal neuronal differentiation in GDNF-treated ENCCs. The human orthologue of Npy2r maps to the HSCR susceptibility locus 4q31.3-q32.3, suggesting a role for NPY2R both in ENS development and in HSCR. PMID- 27266405 TI - Advancing a national cradle-to-grave-to-cradle public health agenda. PMID- 27266406 TI - The interval between primary melanoma excision and sentinel node biopsy is not associated with survival in sentinel node positive patients - An EORTC Melanoma Group study. AB - BACKGROUND: Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe. AIM: To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients. METHODS: Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors. RESULTS: Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00 mm (IQR 1.90-4.80 mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and >=47 days interval: 3.00 mm (1.90-5.00 mm) vs 3.00 mm (1.90-4.43 mm) (p = 0.402). Sentinel node tumor burden was significantly higher in patients operated >=47 days (p = 0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS. CONCLUSIONS: Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients. PMID- 27266407 TI - Nodal skip metastasis is associated with a relatively poor prognosis in thoracic esophageal squamous cell carcinoma. AB - BACKGROUND: Nodal skip metastasis (NSM) is common in esophageal carcinoma, even with different lymph node classification criteria. The prognostic impact of NSM in esophageal carcinoma has been unclear. Some studies found no impact on survival and others found a positive impact. This research was to further investigate the incidence of NSM in patients with thoracic esophageal squamous cell carcinoma (ESCC), and assess its prognostic value in thoracic ESCC. METHODS: We retrospectively analyzed the clinical data of 340 consecutive patients with solitary lymph node metastasis who underwent esophagectomy with three-field lymph node dissection for ESCC at the First Affiliated Hospital of Zhengzhou University from January 2005 to December 2013. The survivals of the patients with NSM or adjacent node metastasis were compared. RESULTS: There were 216 patients with NSM, and 124 patients with adjacent node metastasis. The incidence of NSM in this cohort was 63.5%. No significant difference was found between the patients with NSM and the patients with adjacent node metastasis in age, sex, tumor location, pathologic T stage, histologic grade, tumor length, and the number of resected lymph nodes (all p > 0.05). Patients with NSM had 5-year cumulative survival of 29.2%, which was significantly worse than the 45.6% survival in those with adjacent node metastasis (p < 0.05). CONCLUSION: In conclusion, NSM is associated with a relatively poor prognosis in thoracic ESCC. PMID- 27266408 TI - Systematic use of isolated pancreatic anastomosis after pancreatoduodenectomy: Five years of experience with zero mortality. AB - OBJECTIVE: The aim of this study is to perform a comprehensive evaluation of 5 years of experience with the technique of isolated pancreatic anastomosis reconstruction after pancreatoduodenectomy from the perspective of safety and surgical efficacy using a prospective database. METHODS: The study included all consecutive patients undergoing pancreatoduodenectomy from April 2009 to April 2014 at a single referral center for hepato-pancreato-biliary diseases. The primary endpoint was the safety of the procedures, which was assessed as the occurrence of complications during hospitalization. Ninety-day mortality was also assessed. Postoperative pancreatic fistulas were classified as grade A, B, or C according to the International Study Group of Pancreatic Fistula classification. RESULTS: The study group included 214 consecutive patients with a median age of 60 years who underwent pancreatoduodenectomy. Portal vein resection was performed on 41 patients. Indications for resection were 165 pancreatic head tumors, 33 ampullary tumors, 7 chronic pancreatitis, 3 distal bile duct tumors, and 6 duodenal tumors. There was no perioperative or 90-day mortality in this series. Complications occurred in 68 patients (32%), and 42 patients presented with pancreatic fistulas (19.6%). Grade A fistulas were present in 38 patients. Three patients presented persistent pancreatic fistula and were treated with percutaneous drainage. One patient developed combined pancreatic and biliary fistulas and was reoperated on for pancreatic abscess drainage. CONCLUSIONS: The technique of isolated pancreatic anastomosis by diverting the pancreatic from biliary secretion may contribute to reducing the severity of pancreatic fistulas and therefore the severity of this complication. PMID- 27266419 TI - Pharmacogenetics of anthracyclines. AB - Anthracyclines constitute a fundamental part of the chemotherapy regimens utilized to treat a number of different malignancies both in pediatric and adult patients. These drugs are one of the most efficacious anticancer agents ever invented. On the other hand, anthracyclines are cardiotoxic. Childhood cancer survivors treated with anthracyclines often undergo cardiac complications which are influenced by genetic variations of the patients. The scientific literature comprises numerous investigations in the subject of the pharmacogenetics of anthracyclines. In this review, we provide a comprehensive overview of this research topic. Genetic variants are proposed targets in the personalized treatment in order to individualize dosing and therefore reduce side effects. PMID- 27266420 TI - Predicting Likelihood for Coronary Artery Bypass Grafting After Non-ST-Elevation Myocardial Infarction: Finding the Best Prediction Model. AB - BACKGROUND: Up to half of patients with non-ST-elevation myocardial infarction (NSTEMI) do not receive dual antiplatelet therapy before angiography "pretreatment" because of the risk of increased bleeding if coronary artery bypass grafting (CABG) operation is needed. Several models have been published that predict the likelihood of CABG after NSTEMI, but they have not been independently validated. The purpose of this study was to validate these models and improve the best one. METHODS: We studied patients with NSTEMI who were enrolled in the 24-center Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status (TRIUMPH) registry between 2005 and 2008. Previous CABG prediction models were assessed using c-statistics and calibration assessments to determine the best model. Variables from TRIUMPH likely to be associated with CABG were tested to see whether they could improve the best model's performance. RESULTS: Among 2,473 patients with NSTEMI, 11.8% underwent in-hospital CABG. C-statistics for the Modified Thrombolysis in Myocardial Infarction, Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy Thrombolysis in Myocardial Infarction 18, Poppe, and Global Risk of Acute Coronary Events (GRACE) models were 0.54, 0.61, 0.61, and 0.62, respectively. The GRACE model showed the best discrimination and calibration. From the TRIUMPH registry, preselected variables were added to the GRACE model but did not significantly improve model discrimination. A GRACE model risk score of less than 9 had high sensitivity (96%), thus making it useful for predicting patients with NSTEMI who were at low risk for requiring CABG, which included approximately 21% of patients with NSTEMI. CONCLUSIONS: This study could not improve on the GRACE model, which had the best predictive value for identifying a need for CABG after NSTEMI with a broader range of predicted risk levels and high sensitivity, especially in patients with scores lower than 9. PMID- 27266422 TI - Accuracy of the vivofit activity tracker. AB - The purpose of this study was to examine the accuracy of the vivofit activity tracker in assessing energy expenditure and step count. Thirteen participants wore the vivofit activity tracker for five days. Participants were required to independently perform 1 h of self-selected activity each day of the study. On day four, participants came to the lab to undergo BMR and a treadmill-walking task (TWT). On day five, participants completed 1 h of office-type activities. BMR values estimated by the vivofit were not significantly different from the values measured through indirect calorimetry (IC). The vivofit significantly underestimated EE for treadmill walking, but responded to the differences in the inclination. Vivofit underestimated step count for level walking but provided an accurate estimate for incline walking. There was a strong correlation between EE and the exercise intensity. The vivofit activity tracker is on par with similar devices and can be used to track physical activity. PMID- 27266421 TI - Missed Intrapulmonary Lymph Node Metastasis and Survival After Resection of Non Small Cell Lung Cancer. AB - BACKGROUND: Pathologic nodal stage is a key prognostic factor for patients with surgically resected lung cancer. We previously described the extent of missed intrapulmonary nodal metastasis in a cohort of patients treated at institutions in metropolitan Memphis, TN. With long-term follow-up, we now quantify the survival impact of missed nodal metastasis. METHODS: We conducted a prospective cohort study to evaluate inadvertently discarded lymph nodes in re-dissected remnant lung resection specimens from lung cancer patients. Retrieved material was histologically examined and classified as lymph nodes with and without metastasis. Survival information was obtained from hospital cancer registries. We plotted survival distributions with the use of the Kaplan-Meier method and evaluated them with proportional hazards models that controlled for important demographic and clinical factors. RESULTS: The study included 110 patients who were 54% women and 69% white. Discarded lymph nodes with metastasis were found in 25 patients (23%). Patients with missed lymph node metastasis had an increased risk of death with an unadjusted hazard ratio of 2.0 (p = 0.06) and an adjusted hazard ratio of 1.4 (p = 0.45) compared with patients without missed lymph node metastasis. Patients with more than 2 missed lymph nodes with metastasis had 4.8 times the hazard of death (p = 0.0005) compared with patients without missed lymph node metastasis (adjusted hazard ratio 6.5, p = 0.0001). CONCLUSIONS: Metastasis to inadvertently discarded intrapulmonary lymph nodes from lung cancer resection specimens was associated with reduced survival. A more rigorous gross dissection protocol for lung cancer resection specimens may provide prognostically useful information. PMID- 27266423 TI - Small molecules and antibodies for the treatment of psoriasis: a patent review (2010-2015). AB - INTRODUCTION: Psoriasis is a chronic condition whose therapeutic armamentarium is increasingly being discussed, particularly when compared to past decades. The use of biologic agents has profoundly changed the history of this disease, as well as the management of psoriatic patients. Due to the enormous interest in psoriasis, as demonstrated within the scientific community and pharmaceuticals, new therapeutic targets have been identified and novel patented therapeutics are being tested. AREAS COVERED: This review sought to give an overview of small molecules and antibodies patented in the last five years for the treatment of psoriasis. Therapeutic agents either in the early or advanced phase of development have been described, primarily based on a systematic search using the PubMed Medline database. EXPERT OPINION: Though the recent introduction of new antipsoriatic agents has facilitated the management of long-term psoriasis, there is still a strong desire for alternative therapeutic options. Indeed, there remain unmet needs regarding safety and efficacy of psoriasis treatment that should be addressed. In this context, recently patented drugs may prove valid, interesting, and promising within the therapeutic paradigm. PMID- 27266435 TI - Physician perceptions of Choosing Wisely and drivers of overuse. AB - OBJECTIVES: Little is known regarding physicians' views on health service overuse or their awareness of the American Board of Internal Medicine Foundation's Choosing Wisely campaign. Through the Survey on Overuse and Knowledge of Choosing Wisely, we assessed physician views on hypothesized drivers of overuse and Choosing Wisely. STUDY DESIGN: We designed the survey to investigate physicians' knowledge of, awareness of, and feelings toward Choosing Wisely, along with their concerns about malpractice, perception of patient demand, discomfort with uncertainty, and cost-consciousness. Where possible, we used pre-validated survey instruments. METHODS: We distributed the survey to clinicians practicing at Atrius Health, the largest ambulatory care provider in Massachusetts. We analyzed 584 responses (72% response rate) and calculated 3 previously validated scales. RESULTS: Primary care physicians reported significantly greater awareness of Choosing Wisely (47.2%) than medical specialists (37.4%) and surgical specialists (27%). A majority (62%) of all respondents reported they found uncertainty involved in providing care disconcerting. Approximately one-third felt it unfair to ask physicians to be both cost-conscious and concerned with welfare, thought too much emphasis was placed on costs, and thought doctors were too busy to worry about costs. Surgical specialists were more concerned about malpractice, whereas primary care physicians reported feeling significantly more pressure from patients for tests and procedures. CONCLUSIONS: Knowledge of Choosing Wisely is limited, but primary care physicians are more aware of the campaign than specialists. Although hypothesized drivers of overuse are prevalent, most physicians support cost-consciousness in medicine and embrace their responsibility in reducing costs. PMID- 27266436 TI - Medicaid managed care penetration and drug utilization for patients with serious mental illness. AB - OBJECTIVES: State Medicaid programs are under increasing pressure to contain pharmaceutical spending. Many states have attempted to limit spending through greater Medicaid managed care penetration, which rose nationally from 54.5% in 1999 to 74.9% in 2011. It is not clear how this expansion has affected beneficiaries with serious mental illness (SMI)-a vulnerable population that often has their drug spending "carved out" from their managed care benefit. We sought to assess the association between managed care penetration and pharmaceutical spending on drugs for SMIs in these states. STUDY DESIGN: Retrospective cohort study. METHODS: State-year observations were constructed to study the relationship between managed care penetration and pharmaceutical spending on drugs for SMIs over the period 1999 to 2011. We analyzed the relationship using both cross-sectional and panel-data methods. RESULTS: Our cross-sectional analyses suggested that carve-out states with greater managed care penetration spend significantly less per enrollee on pharmaceuticals for the treatment of mental disorders: our panel data analyses did not generate statistically meaningful results. CONCLUSIONS: Future studies should address whether any effects of managed care on mental health prescription utilization and spending reflect improved care coordination or worsening access to valuable care for the population with SMI. PMID- 27266437 TI - Implementing a hybrid approach to select patients for care management: variations across practices. AB - OBJECTIVES: Appropriate selection of patients is key to the success of care management programs (CMPs). Hybrid patient selection approaches, in which large data assets are culled to develop a list of patients for more targeted clinical review, are increasingly common. We sought to describe the patient and practice characteristics associated with high-risk patient identification and selection for a CMP during clinical review, and to explore variation across primary care practices. STUDY DESIGN: Retrospective cohort study. METHODS: Standardized estimates of Medicare beneficiaries identified as high risk for poor outcomes and high medical expense, and appropriate for a CMP within a large Pioneer Accountable Care Organization, were developed using mixed effects logistic models. Study subjects were 2685 Medicare beneficiaries aged over 18 (includes individuals eligible for Medicare due to a disability) aligned to 35 primary care practices in 2013. RESULTS: Independent predictors of patient identification as high risk include older age; higher risk score; recent increases in medical conditions; higher numbers of medical hospitalizations, skilled nursing facility days, and primary care physician visits; and shorter relationships with the primary care physician. Older age, and lower income, but no prior hospice use were independently associated with patient selection for a CMP among the subset of patients identified as being high risk. Adjusted predicted percents of high risk patients varied significantly across practices overall and for 5 of the 6 patient characteristics that were independently associated with identification as high risk. CONCLUSIONS: Inconsistency in high-risk patient identification and selection for a CMP may reflect differences in practice resources, but also highlight the need for continual training and feedback in order to protect against unintentional biases. PMID- 27266438 TI - Clinical interventions addressing nonmedical health determinants in Medicaid managed care. AB - OBJECTIVES: We aimed to examine how interventions addressing social determinants of health (SDH) have been adopted in the context of Medicaid managed care organizations (MMCOs), which serve a large proportion of patients with social and economic barriers to good health. STUDY DESIGN: We designed a systematic literature review to examine how SDH interventions have been adopted in MMCOs. METHODS: The review included published articles from PubMed, Scopus, and Business Source databases, as well as review articles published in the gray literature and articles recommended by the study's National Advisory Committee to identify interventions describing how MMCOs have invested in interventions that address patients' SDH. To be included in the review, an article had to describe an intervention that was based in the United States, be supported financially by an MMCO, focus on at least 1 SDH, and be integrated into clinical care delivery. RESULTS: Twenty-five programs were identified in either commercial Medicaid or Medicaid-only MCOs that involved interventions integrated into clinical care and related to SDH. Interventions varied widely in terms of target populations and target SDH, and rarely included rigorous evaluations. The majority of programs described "case management services" that did not clearly distinguish between the delivery of medical and social interventions. CONCLUSIONS: Despite a growing interest in clinical interventions that address SDH, little information is available in the published literature about the extent to which these interventions have been adopted by MMCOs, where they are likely to have early traction based both on capitated funding structures and the low-income populations served. PMID- 27266439 TI - Greater potential cost savings with biosimilar use. PMID- 27266440 TI - Multivariate Analysis to Predict the Horizontal Anterior Chamber Diameter from Other Anterior Chamber Parameters Using Scheimpflug Imaging: Is There a Better Method Than Adding a Fixed Constant? AB - PURPOSE: To evaluate the predictive association between the horizontal anterior chamber diameter (HACD) and other measurements using Scheimpflug imaging, and to assess whether a method superior to using fixed constants can be proposed. METHODS: This hospital-based study was performed in the Cornea and Refractive Surgery Services, New Medical Center (NMC) specialty hospital, Abu Dhabi. Initially, 100 candidates were included serially in the model building group (group1). All candidates underwent detailed evaluation and Scheimpflug imaging (CSO, Sirus, Italy). Subsequently, another 100 candidates were included serially in the validation group (group 2). Candidates in both groups underwent the same tests. RESULTS: In group 1, the mean HACD was 12.25 +/- 0.48 mm. This measurement correlated significantly with the horizontal visible iris diameter (HVID), anterior chamber depth, angle (ACA), and volume (ACV) (r = 0.2-0.7). The overall regression equation was HACD = 5.62 + 0.01 * ACV + 0.45 * HVID - 0.013 * ACA (adjusted R2 = 0.66, p < 0.001). Situation-based equations derived from the outcomes of group 1 were tested in group 2. Equation A included all factors found significant during model-building, Equation B included only non-volumetric significant factors, and situation C only included the HVID. Equations D through F used direct substitution by HVID plus a constant to predict HACD (the constant was 0.0, 0.5, and 1.0 for Equations D, E, and F, respectively). The predicted HACD (pHACD) was within +/-0.5 mm of the actual HACD (aHACD) in 93%, 88%, 87%, 83%, 69%, and 16% case for Equations A, B, C, D, E, and F, respectively. The mean prediction error was -0.14 +/- 0.27 mm (p = 0.08), -0.15 +/- 0.28 mm (p = 0.03), 0.18 +/- 0.30 mm (p = 0.001), -0.18 +/- 0.32 mm (p < 0.001), 0.33 +/- 0.35 mm (p < 0.001), and 0.83 +/- 0.35 mm (p < 0.001) for Equations A, B, C, D, E, and F, respectively. CONCLUSION: Regression equations using Scheimpflug-derived anterior chamber parameters may predict HACD to varying degrees, depending on the input parameters. Adding 0.5 or 1.0 mm to the corneal diameter (CD) to estimate the HACD is not recommended. PMID- 27266441 TI - HDTD: analyzing multi-tissue gene expression data. AB - MOTIVATION: By collecting multiple samples per subject, researchers can characterize intra-subject variation using physiologically relevant measurements such as gene expression profiling. This can yield important insights into fundamental biological questions ranging from cell type identity to tumour development. For each subject, the data measurements can be written as a matrix with the different subsamples (e.g. multiple tissues) indexing the columns and the genes indexing the rows. In this context, neither the genes nor the tissues are expected to be independent and straightforward application of traditional statistical methods that ignore this two-way dependence might lead to erroneous conclusions. Herein, we present a suite of tools embedded within the R/Bioconductor package HDTD for robustly estimating and performing hypothesis tests about the mean relationship and the covariance structure within the rows and columns. We illustrate the utility of HDTD by applying it to analyze data generated by the Genotype-Tissue Expression consortium. AVAILABILITY AND IMPLEMENTATION: The R package HDTD is part of Bioconductor. The source code and a comprehensive user's guide are available at http://bioconductor.org/packages/release/bioc/html/HDTD.html CONTACT: : A.Touloumis@brighton.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27266442 TI - Paclitaxel-Loaded Mixed Micelles Enhance Ovarian Cancer Therapy through Extracellular pH-Triggered PEG Detachment and Endosomal Escape. AB - Although PEGylation allows a drug delivery vehicle to have prolonged blood circulation time, it faces the problem of reduced cellular uptake. Removal of the polyethylene glycol (PEG)-shell at the appropriate time through tumor microenvironment triggers could be a feasible solution to this problem. Here, paclitaxel (PTX)-loaded mixed micelles (PTX-mM) self-assembled from stearate modified hyaluronic acid (SHA), mPEG-b-poly(beta-amino ester) (mPEG-b-PAE), and ethylene acetyl-b-poly(beta-amino ester) (EA-b-PAE) were developed. In the preparation of PTX-mM, SHA micelles were coated with EA-b-PAE followed by coloading of PTX and mPEG-b-PAE. PTX-mM were capable of extracellular pH triggered PEG-detachment and poly(beta-amino ester) (PAE)-mediated endosomal escape. When the pH was changed from pH 7.4 to pH 6.8, the particle size of PTX mM significantly decreased from 97.5 +/- 4.4 to 71.5 +/- 2.3 nm. It also resulted in rapid and complete release of mPEG-b-PAE from PTX-mM as monitored using quartz crystal microbalance (QCM) technology. PTX-mM capable of PEG detachment provided significant enhancement of PTX accumulation in SKOV-3 cells compared to PEG nondetachable PTX-mM. Interestingly, intracellular transport studies using confocal laser scanning microscopy (CLSM) showed that EA-b-PAE could promote the escape of micelles from endolysosomes. The half-maximal inhibitory concentration (IC50) of PTX-mM against SKOV-3 cells was 5.7 MUg/mL, and PTX-mM containing 20 MUg/mL of PTX induced apoptosis in 53.0% of the cell population. PTX-mM exhibited a highly prolonged elimination half-life (t1/2, 2.83 +/- 0.37 h) and improved area under the curve (AUC, 7724.82 +/- 1190.75 ng/mL/h) than the PTX-loaded SHA micelles (PTX-M). Furthermore, PTX-mM showed the highest tumor inhibition rate (64.9%) and the longest survival time (53 days) against the SKOV-3 ovarian cancer xenograft models among all formulations. Taken together, the results suggested that PTX-mM have potential as an efficient anticancer formulation in treatment of ovarian cancer. PMID- 27266444 TI - DNP-Enhanced Ultrawideline Solid-State NMR Spectroscopy: Studies of Platinum in Metal-Organic Frameworks. AB - Ultrawideline dynamic nuclear polarization (DNP)-enhanced (195)Pt solid-state NMR (SSNMR) spectroscopy and theoretical calculations are used to determine the coordination of atomic Pt species supported within the pores of metal-organic frameworks (MOFs). The (195)Pt SSNMR spectra, with breadths reaching 10 000 ppm, were obtained by combining DNP with broadbanded cross-polarization and CPMG acquisition. Although the DNP enhancements in static samples are lower than those typically observed under magic-angle spinning conditions, the presented measurements would be very challenging using the conventional SSNMR methods. The DNP-enhanced ultrawideline NMR spectra served to separate signals from cis- and trans-coordinated atomic Pt(2+) species supported on the UiO-66-NH2 MOF. Additionally, the data revealed a dominance of kinetic effects in the formation of Pt(2+) complexes and the thermodynamic effects in their reduction to nanoparticles. A single cis-coordinated Pt(2+) complex was confirmed in MOF-253. PMID- 27266443 TI - Mindfulness training increases cooperative decision making in economic exchanges: Evidence from fMRI. AB - Emotions have been shown to exert influences on decision making during economic exchanges. Here we investigate the underlying neural mechanisms of a training regimen which is hypothesized to promote emotional awareness, specifically mindfulness training (MT). We test the hypothesis that MT increases cooperative economic decision making using fMRI in a randomized longitudinal design involving 8weeks of either MT or active control training (CT). We find that MT results in an increased willingness to cooperate indexed by higher acceptance rates to unfair monetary offers in the Ultimatum Game. While controlling for acceptance rates of monetary offers between intervention groups, subjects in the MT and CT groups show differential brain activation patterns. Specifically, a subset of more cooperative MT subjects displays increased activation in the septal region, an area linked to social attachment, which may drive the increased willingness to express cooperative behavior in the MT cohort. Furthermore, MT resulted in attenuated activity in anterior insula compared with the CT group in response to unfair monetary offers post-training, which may suggest that MT enables greater ability to effectively regulate the anterior insula and thereby promotes social cooperation. Finally, functional connectivity analyses show a coupling between the septal region and posterior insula in the MT group, suggesting an integration of interoceptive inputs. Together, these results highlight that MT may be employed in contexts where emotional regulation is required to promote social cooperation. PMID- 27266445 TI - Evaluation of postural stability in youth athletes: the relationship between two rating systems. AB - OBJECTIVES: The Balance Error Scoring System (BESS) has been documented as a useful way to evaluate postural control following sport-related concussions sustained by youth athletes. However, limitations have been reported with its use due to the reliance on visual observation as the primary measurement outcome. The primary purpose of this study was to examine the correlation between the modified BESS (mBESS) as rated by a clinician and a simultaneous analysis performed by an integrated video-force plate system. The secondary purpose was to assess if a history of prior concussion affected postural control. METHODS: A group of healthy youth athletes (n = 398; mean age 13.7 +/- 2.4 years) completed the mBESS while simultaneously undergoing an integrated video-force plate evaluation to measure postural stability. Spearman rank-order correlations were used to determine the strength of correlation between the 2 rating systems. In addition, performance on the mBESS between those with and without a history of concussion was compared using univariate ANCOVAs. RESULTS: A moderately high correlation was found during single-leg stance (rho = -0.64, p < .001), while a weak correlation was found during tandem stance (rho = -0.30, p < .001). No postural control differences were found between groups with and without a concussion history. CONCLUSION: The video-force plate rating system correlates well with the clinician rating during the single-leg stance of the mBESS, but not during double leg or tandem stances. A history of concussion did not affect mBESS scores. PMID- 27266446 TI - Engineering cell-based therapies to interface robustly with host physiology. AB - Engineered cell-based therapies comprise a rapidly growing clinical technology for treating disease by leveraging the natural capabilities of cells, including migration, information transduction, and biosynthesis and secretion. There now exists a substantial portfolio of intracellular and extracellular sensors that enable bioengineers to program cells to execute defined responses to specific changes in state or environmental cues. As our capability to construct more sophisticated cellular programs increases, assessing and improving the degree to which cell-based therapies perform as desired in vivo will become an increasingly important consideration and opportunity for technological advancement. In this review, we seek to describe both current capabilities and potential needs for building cell-based therapies that interface with host physiology in a manner that is robust - a phrase we use in this context to describe the achievement of therapeutic efficacy across a range of patients and implementations. We first review the portfolio of sensors and outputs currently available for use in cell based therapies by highlighting key advancements and current gaps. Then, we propose a conceptual framework for evaluating and pursuing robust clinical performance of engineered cell-based therapies. PMID- 27266474 TI - Depressive and anxiety disorders and short leukocyte telomere length: mediating effects of metabolic stress and lifestyle factors. AB - BACKGROUND: Depressive and anxiety disorders are associated with shorter leukocyte telomere length (LTL), an indicator of cellular aging. It is, however, unknown which pathways underlie this association. This study examined the extent to which lifestyle factors and physiological changes such as inflammatory or metabolic alterations mediate the relationship. METHOD: We applied mediation analysis techniques to data from 2750 participants of the Netherlands Study of Depression and Anxiety. LTL was assessed using quantitative polymerase chain reaction. Independent variables were current depressive (30-item Inventory of Depressive Symptoms - Self Report) and anxiety (21-item Beck's Anxiety Inventory) symptoms and presence of a depressive or anxiety disorder diagnosis based on DSM IV; mediator variables included physiological stress systems, metabolic syndrome components and lifestyle factors. RESULTS: Short LTL was associated with higher symptom severity (B = -2.4, p = 0.002) and current psychiatric diagnosis (B = 63.3, p = 0.024). C-reactive protein, interleukin-6, waist circumference, triglycerides, high-density lipoprotein cholesterol and cigarette smoking were significant mediators in the relationship between psychopathology and LTL. When all significant mediators were included in one model, the effect sizes of the relationships between LTL and symptom severity and current diagnosis were reduced by 36.7 and 32.7%, respectively, and the remaining direct effects were no longer significant. CONCLUSIONS: Pro-inflammatory cytokines, metabolic alterations and cigarette smoking are important mediators of the association between depressive and anxiety disorders and LTL. This calls for future research on intervention programs that take into account lifestyle changes in mental health care settings. PMID- 27266475 TI - Carbon nanotube (CNT) and nanofibrillated cellulose (NFC) reinforcement effect on thermoplastic polyurethane (TPU) scaffolds fabricated via phase separation using dimethyl sulfoxide (DMSO) as solvent. AB - Although phase separation is a simple method of preparing tissue engineering scaffolds, it suffers from organic solvent residual in the scaffold. Searching for nontoxic solvents and developing effective solvent removal methods are current challenges in scaffold fabrication. In this study, thermoplastic polyurethane (TPU) scaffolds containing carbon nanotubes (CNTs) or nanofibrillated cellulose fibers (NFCs) were prepared using low toxicity dimethyl sulfoxide (DMSO) as a solvent. The effects of two solvent removal approaches on the final scaffold morphology were studied. The freeze drying method caused large pores, with small pores on the pore walls, which created connections between the pores. Meanwhile, the leaching and freeze drying method led to interconnected fine pores with smaller pore diameters. The nucleation effect of CNTs and the phase separation behavior of NFCs in the TPU solution resulted in significant differences in the microstructures of the resulting scaffolds. The mechanical performance of the nanocomposite scaffolds with different morphologies was investigated. Generally, the scaffolds with a fine pore structure showed higher compressive properties, and both the CNTs and NFCs improved the compressive properties of the scaffolds, with greater enhancement found in TPU/NFC nanocomposite scaffolds. In addition, all scaffolds showed good sustainability under cyclical load bearing, and the biocompatibility of the scaffolds was verified via 3T3 fibroblast cell culture. PMID- 27266476 TI - An approach to scaling size effect on strength of quasi-brittle biomedical materials. AB - Two-parameter Weibull statistics is commonly used for characterizing and modeling strength distribution of biomedical materials and its size dependence. The calibrated scale parameter and shape factor are usually sensitive to specimen size. Since Weibull statistics is subject to the weakest link postulate, this work proposed to directly resort to the weakest-link formulation for the cumulative failure probability to characterize size effect on strength distribution of quasi-brittle biomedical materials. As a preliminary examination, the approach was assessed by two sets of published strength data. It shows that the resultant expression for the cumulative probability follows either Weibull distribution or other type of distributions. The calibrated model parameters are independent of specimen size, so they can be used to transfer strength distribution from one set of specimens to another set of specimens with geometrical similarity under same loading mode. These initial results motivate a more comprehensive validation of the proposed approach to proceed via a larger set of case studies covering different quasi-brittle biomedical materials over a wider range of size variation. PMID- 27266477 TI - C-Au Covalently Bonded Molecular Junctions Using Nonprotected Alkynyl Anchoring Groups. AB - We report on an approach to realize carbon-gold (C-Au) bonded molecular junctions without the need for an additive to deprotect the alkynyl carbon as endstanding anchor group. Using the mechanically controlled break junction (MCBJ) technique, we determine the most probable conductance value of a family of alkynyl terminated oligophenylenes (OPA(n)) connected to gold electrodes through such an akynyl moiety in ambient conditions. The molecules bind to the gold leads through an sp-hybridized carbon atom at each side. Comparing our results with other families of molecules that present organometallic C-Au bonds, we conclude that the conductance of molecules contacted via an sp-hybridized carbon atom is lower than the ones using sp(3) hybridization due to strong differences in the coupling of the conducting orbitals with the gold leads. PMID- 27266479 TI - BF3-Etherate-Promoted Cascade Reaction of 2-Alkynylanilines with Nitriles: One Pot Assembly of 4-Amido-Cinnolines. AB - A BF3-etherate-promoted cascade reaction of nitriles with 2-alkynylanilines is described. This method achieves the formation of two new C-N bonds through a reaction sequence of diazotization with t-BuONO, nucleophilic addition of the alkyne to the BF3-coordinated diazonium ion, followed by nitrile addition to the intermediary vinyl cation and hydrolysis. The method provides efficient and general access to a variety of 4-amido-cinnolines. Notable features of the method include its broad functional group tolerance and avoidance of transition metals. PMID- 27266478 TI - High-Performance Three-Dimensional Tubular Nanomembrane Sensor for DNA Detection. AB - We report an ultrasensitive label-free DNA biosensor with fully on-chip integrated rolled-up nanomembrane electrodes. The hybridization of complementary DNA strands (avian influenza virus subtype H1N1) is selectively detected down to attomolar concentrations, an unprecedented level for miniaturized sensors without amplification. Impedimetric DNA detection with such a rolled-up biosensor shows 4 orders of magnitude sensitivity improvement over its planar counterpart. Furthermore, it is observed that the impedance response of the proposed device is contrary to the expected behavior due to its particular geometry. To further investigate this difference, a thorough model analysis of the measured signal and the electric field calculation is performed, revealing enhanced electron hopping/tunneling along the DNA chains due to an enriched electric field inside the tube. Likewise, conformational changes of DNA might also contribute to this effect. Accordingly, these highly integrated three-dimensional sensors provide a tool to study electrical properties of DNA under versatile experimental conditions and open a new avenue for novel biosensing applications (i.e., for protein, enzyme detection, or monitoring of cell behavior under in vivo like conditions). PMID- 27266481 TI - Theoretical Study of the Reactions of Methane and Ethane with Electronically Excited N2(A(3)Sigmau(+)). AB - Comprehensive quantum chemical analysis with the usage of density functional theory and post-Hartree-Fock approaches were carried out to study the processes in the N2(A(3)Sigmau(+)) + CH4 and N2(A(3)Sigmau(+)) + C2H6 systems. The energetically favorable reaction pathways have been revealed on the basis of the examination of potential energy surfaces. It has been shown that the reactions N2(A(3)Sigmau(+)) + CH4 and N2(A(3)Sigmau(+)) + C2H6 occur with very small or even zero activation barriers and, primarily, lead to the formation of N2H + CH3 and N2H + C2H5 products, respectively. Further, the interaction of these species can give rise the ground state N2(X(1)Sigmag(+)) and CH4 (or C2H6) products, i.e., quenching of N2(A(3)Sigmau(+)) by CH4 and C2H6 molecules is the complex two step process. The possibility of dissociative quenching in the course of the interaction of N2(A(3)Sigmau(+)) with CH4 and C2H6 molecules has been analyzed on the basis of RRKM theory. It has been revealed that, for the reaction of N2(A(3)Sigmau(+)) with CH4, the dissociative quenching channel could occur with rather high probability, whereas in the N2(A(3)Sigmau(+)) + C2H6 reacting system, an analogous process was little probable. Appropriate rate constants for revealed reaction channels have been estimated by using a canonical variational theory and capture approximation. The estimations showed that the rate constant of the N2(A(3)Sigmau(+)) + C2H6 reaction path is considerably greater than that for the N2(A(3)Sigmau(+)) + CH4 one. PMID- 27266480 TI - Metal Azolate/Carboxylate Frameworks as Catalysts in Oxidative and C-C Coupling Reactions. AB - The five metal azolate/carboxylate (MAC) compounds [Cd(dmpzc)(DMF)(H2O)] (Cd dmpzc), [Pd(H2dmpzc)2Cl2] (Pd-dmpzc), [Cu(Hdmpzc)2] (Cu-dmpzc), [Zn4O(dmpzc)3].Solv (Zn-dmpzc.S), and [Co4O(dmpzc)3].Solv (Co-dmpzc.S) were isolated by coupling 3,5-dimethyl-1H-pyrazol-4-carboxylic acid (H2dmpzc) to cadmium(II), palladium(II), copper(II), zinc(II), and cobalt(II) salts. While Cd dmpzc and Pd-dmpzc had never been prepared in the past, for Cu-dmpzc, Zn-dmpzc.S, and Co-dmpzc.S we optimized alternative synthetic paths that, in the case of the copper(II) and cobalt(II) derivatives, are faster and grant higher yields than the previously reported ones. The crystal structure details were determined ab initio (Cd-dmpzc and Pd-dmpzc) or refined (Cu-dmpzc, Zn-dmpzc.S, and Co-dmpzc.S) by means of powder X-ray diffraction (PXRD). While Cd-dmpzc is a nonporous 3D MAC framework, Pd-dmpzc shows a 3D hybrid coordination/hydrogen-bonded network, in which Pd(H2dmpzc)2Cl2 monomers are present. The thermal behavior of the five MAC compounds was investigated by coupling thermal analysis to variable-temperature PXRD. Their catalytic activity was assessed in oxidative and C-C coupling reactions, with the copper(II) and cadmium(II) derivatives being the first nonporous MAC frameworks to be tested as catalysts. Cu-dmpzc is the most active catalyst in the partial oxidation of cyclohexane by tert-butyl hydroperoxide in acetonitrile (yields up to 12% after 9 h) and is remarkably active in the solvent free microwave-assisted oxidation of 1-phenylethanol to acetophenone (yields up to 99% at 120 degrees C in only 0.5 h). On the other hand, activated Zn-dmpzc.S (Zn-dmpzc) is the most active catalyst in the Henry C-C coupling reaction of aromatic aldehydes with nitroethane, showing appreciable diastereoselectivity toward the syn-nitroalkanol isomer (syn:anti selectivity up to 79:21). PMID- 27266447 TI - Imaging the pharmacology of nanomaterials by intravital microscopy: Toward understanding their biological behavior. AB - Therapeutic nanoparticles (NPs) can deliver cytotoxic chemotherapeutics and other drugs more safely and efficiently to patients; furthermore, selective delivery to target tissues can theoretically be accomplished actively through coating NPs with molecular ligands, and passively through exploiting physiological "enhanced permeability and retention" features. However, clinical trial results have been mixed in showing improved efficacy with drug nanoencapsulation, largely due to heterogeneous NP accumulation at target sites across patients. Thus, a clear need exists to better understand why many NP strategies fail in vivo and not result in significantly improved tumor uptake or therapeutic response. Multicolor in vivo confocal fluorescence imaging (intravital microscopy; IVM) enables integrated pharmacokinetic and pharmacodynamic (PK/PD) measurement at the single-cell level, and has helped answer key questions regarding the biological mechanisms of in vivo NP behavior. This review summarizes progress to date and also describes useful technical strategies for successful IVM experimentation. PMID- 27266482 TI - Molecular characterization and phylogenetic analysis of Fasciola gigantica from western Java, Indonesia. AB - Fasciola gigantica and aspermic (hybrid) Fasciola flukes are thought to be distributed in Southeast Asian countries. The objectives of this study were to investigate the distribution of these flukes from unidentified ruminants in western Java, Indonesia, and to determine their distribution history into the area. Sixty Fasciola flukes from western Java were identified as F. gigantica based on the nucleotide sequences of the nuclear phosphoenolpyruvate carboxykinase (pepck) and DNA polymerase delta (pold) genes. The flukes were then analyzed phylogenetically based on the nucleotide sequence of the mitochondrial NADH dehydrogenase subunit 1 (nad1) gene, together with Fasciola flukes from other Asian countries. All but one F. gigantica fluke were classified in F. gigantica haplogroup C, which mainly contains nad1 haplotypes detected in flukes from Thailand, Vietnam, and China. A population genetic analysis suggested that haplogroup C spread from Thailand to the neighboring countries including Indonesia together with domestic ruminants, such as the swamp buffalo, Bubalus bubalis. The swamp buffalo is one of the important definitive hosts of Fasciola flukes in Indonesia, and is considered to have been domesticated in the north of Thailand. The remaining one fluke displayed a novel nad1 haplotype that has never been detected in the reference countries. Therefore, the origin of the fluke could not be established. No hybrid Fasciola flukes were detected in this study, in contrast to neighboring Asian countries. PMID- 27266483 TI - First confirmed human case of Diphyllobothrium stemmacephalum infection and molecular verification of the synonymy of Diphyllobothrium yonagoense with D. stemmacephalum (Cestoda: Diphyllobothriidea). AB - Several tapeworm species in the genus Diphyllobothrium Cobbold, 1858 have uncertain taxonomic positions, leading to taxonomic confusion as well as misdiagnosis of infections. Taxonomic revision based on DNA sequence analysis is considered necessary to resolve the taxonomy of several cases, including that between Diphyllobothrium stemmacephalum, the type species of the genus, and Diphyllobothrium yonagoense. Diphyllobothrium yonagoense was synonymized with D. stemmacephalum based on morphological observations by Andersen (1987), however no molecular studies have been undertaken to verify the validity of this synonymization. In the present study, the first human case confirmed molecularly as D. stemmacephalum infection is reported, and the validity of the synonymization of D. yonagoense with D. stemmacephalum was assessed based on molecular phylogenetics. Diphyllobothrium stemmacephalum and D. yonagoense grouped into the same clades with high bootstrap confidence values for both cox1 and nad3. Genetic distances between the two taxa were very small (0.000-0.012 and 0.000-0.017 for cox1 and nad3, respectively) and were considered to fall within the range of intraspecific variation. Using these molecular analyses, this study verified molecularly that D. yonagoense is a junior synonym of D. stemmacephalum. Further, the closer phylogenetic relationship between D. stemmacephalum and Diplogonoporus species rather than other diphyllobothriids, including Diphyllobothrium nihonkaiense and Diphyllobothrium latum, was corroborated. The genus name for D. nihonkaiense and D. latum is also discussed. PMID- 27266484 TI - [Formula: see text]Interpreting change on the neurobehavioral symptom inventory and the PTSD checklist in military personnel. AB - OBJECTIVE: The purpose of this study was to examine the prevalence and stability of symptom reporting in a healthy military sample and to develop reliable change indices for two commonly used self-report measures in the military health care system. PARTICIPANTS AND METHOD: Participants were 215 U.S. active duty service members recruited from Fort Bragg, NC as normal controls as part of a larger study. Participants completed the Neurobehavioral Symptom Inventory (NSI) and Posttraumatic Checklist (PCL) twice, separated by approximately 30 days. RESULTS: Depending on the endorsement level used (i.e. ratings of 'mild' or greater vs. ratings of 'moderate' or greater), approximately 2-15% of this sample met DSM-IV symptom criteria for Postconcussional Disorder across time points, while 1-6% met DSM-IV symptom criteria for Posttraumatic Stress Disorder. Effect sizes for change from Time 1 to Time 2 on individual symptoms were small (Cohen's d = .01 to .13). The test-retest reliability for the NSI total score was r = .78 and the PCL score was r = .70. An eight-point change in symptom reporting represented reliable change on the NSI total score, with a seven-point change needed on the PCL. CONCLUSIONS: Postconcussion-like symptoms are not unique to mild TBI and are commonly reported in a healthy soldier sample. It is important for clinicians to use normative data when evaluating a service member or veteran and when evaluating the likelihood that a change in symptom reporting is reliable and clinically meaningful. PMID- 27266485 TI - Design, synthesis and computational evaluation of a novel intermediate salt of N cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide as potential potassium channel blocker in epileptic paroxysmal seizures. AB - The narrow therapeutic range and limited pharmacokinetics of available Antiepileptic drugs (AEDs) have raised serious concerns in the proper management of epilepsy. To overcome this, the present study attempts to identify a candidate molecule targeting voltage gated potassium channels anticipated to have superior pharmacological than existing potassium channel blockers. The compound was synthesized by reacting (S)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4] benzodiazepine5,11(10H,11aH)-dione with 4-(Trifluoromethyl) benzoic acid (C8H5F3O2) in DMF and N,N'-dicyclohexylcarbodiimide (DCC) which lead to the formation of an intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4 (trifluoromethyl)benzamide with a perfect crystalline structure. The structure of the compound was characterized by FTIR, 1H NMR and 13C NMR analysis. The crystal structure is confirmed by single crystal X-ray diffraction analysis. The Structure-Activity Relationship (SAR) studies revealed that substituent of fluoro or trifluoromethyl moiety into the compound had a great effect on the biological activity in comparison to clinically used drugs. Employing computational approaches the compound was further tested for its affinity against potassium protein structure by molecular docking in addition, bioactivity and ADMET properties were predicted through computer aided programs. PMID- 27266486 TI - Spectrum-Based Electrochemiluminescent Immunoassay with Ternary CdZnSe Nanocrystals as Labels. AB - Conventional electrochemiluminescence (ECL) research has been performed by detecting the total photons (i.e., the ECL intensity). Herein, systematic spectral exploration on the ECL of dual-stabilizers-capped ternary CdZnSe nanocrystals (NCs) and its sensing application were carried out on a homemade ECL spectral acquiring system. The ternary CdZnSe NCs could be repeatedly injected with electrons via some electrochemical ways and then result in strong cathodic ECL with the coupling of ammonium persulfate. ECL spectrum of the CdZnSe NCs was almost identical to corresponding photoluminescence spectrum, indicating that the excited states of CdZnSe NCs in ECL were essentially the same as those in photoluminescence. Importantly, after being labeled to the probe antibody (Ab2) of alpha-fetal protein (AFP) antigen, the ternary NCs in the Ab2|NCs conjugates could preserve their ECL spectrum very well. A spectrum-based ECL immunoassay was consequently proposed with the CdZnSe NCs as ECL tags and AFP as target molecules. The limit of detection is 0.010 pg/mL, with a signal-to-noise (S/N) ratio of 3, indicating a sensitive ECL sensing strategy that was different from the conventional ones. This work might open a pathway to the spectrally resolved ECL analysis with even-higher S/N ratios than the fluorescent analysis. PMID- 27266487 TI - Electrochemical Stability Window of Imidazolium-Based Ionic Liquids as Electrolytes for Lithium Batteries. AB - This paper presents the computational assessment of the electrochemical stability of a series of alkyl methylimidazolium-based ionic liquids for their use as lithium battery electrolytes. The oxidation and reduction potentials of the constituent cation and anion of each ionic liquid with respect to a Li(+)/Li reference electrode were calculated using density functional theory following the method of thermodynamic cycles, and the electrochemical stability windows (ESW)s of these ionic liquids were obtained. The effect of varying the length of alkyl side chains of the methylimidazolium-based cations on the redox potentials and ESWs was investigated. The results show that the limits of the ESWs of these methylimidazolium-based ionic liquids are defined by the oxidation potential of the anions and the reduction potential of alkyl-methylimidazolium cations. Moreover, ionic liquids with [PF6](-) anion have a wider ESW. In addition to characterizing structure-function relationships, the accuracy of the computational approach was assessed through comparisons of the data against experimental measurements of ESWs. The potentials calculated by the thermodynamic cycle method are in good agreement with the experimental data while the HOMO/LUMO method overestimates the redox potentials. This work demonstrates that these approaches can provide guidance in selecting ionic liquid electrolytes when designing high-voltage rechargeable batteries. PMID- 27266488 TI - [Promoting the study of pituitary tumor translational medicine in the big data era]. PMID- 27266489 TI - [Improve the clinic level of pituitary diseases through expediting the building of China Pituitary Disease Registry Center]. PMID- 27266490 TI - [Analysis of curative effect of surgical therapy for male prolactinoma]. AB - OBJECTIVE: To summarize the treatment outcome of surgery for male prolactinoma. METHODS: One hundred and eighty-four cases of male prolactinoma who underwent surgery were analyzed retrospectively.The average age of patients was 36.3 years, and the mean course was 41.9 months.The main clinical manifestation included sexual dysfunction (47.4%), headache (55.9%) and visual disturbance (46.7%). The serum prolactin levels ranged from 6.83 to 9 325.32 nmol/L.The size of tumors varied from 6 mm to 70 mm.Suprasellar adenoma with visual deficits accounted for 40.7%. 98.9% patients underwent pituitary adenoma resection via single nasal transsphenoidal approach. RESULTS: Postoperative pathological Ki-67 index of most patients (45.1%) were less than 1%.After surgical therapy, 163 patients (88.6%) got relief of symptoms, 57 patients (31.0%) achieved initial remission, and 26 patients (45.6%) unfortunately recurred. The possibility of gross resection decreased as tumor size increased (P<0.05). Preoperative PRL had no significant relation with both tumor size and extent of resection (P>0.05). The favorable prognosis predictive factors included microadenoma, intrasellar adenoma and Ki-67 index<=3 (P<0.01). CONCLUSION: Male prolactinomas is an invasive tumor with higher serum prolactin level.Tumor size could predict degree of gross resection while predictors for recurrence include tumor size, growth pattern and Ki-67 index. PMID- 27266491 TI - [Quality of life of patients with nonfunctioning pituitary adenoma: a meta analysis]. AB - OBJECTIVE: To evaluate the quality of life (QoL) of patients with nonfunctioning pituitary adenoma (NFPA) after systematic treatment. METHODS: We searched all published articles involving in the QoL of patients with NFPA on line, and analyzed the results by the Revman5.3 software. RESULTS: Five studies met the criteria of meta-analysis.The results of meta-analysis wereas follows: Physical function MD=0.76, 95%CI (-4.13, 5.64 ), P=0.76; Physical prole MD=-2.05, 95%CI ( 7.41, 3.31), P=0.45; Body pain MD=3.50, 95%CI (1.11, 5.90), P=0.004; General health MD=-7.19, 95%CI (-12.77, -1.61), P=0.01; Vatility MD=-3.48, 95%CI (-7.39, 0.43), P=0.08; Social function MD=-4.64, 95%CI (-6.99, -2.38), P<0.000 1; Mental health MD=-0.05, 95%CI (-2.30, 2.20), P=0.96; Role emotion MD=-5.08, 95%CI ( 8.20, -1.91), P=0.002. CONCLUSIONS: This meta-analysisindicated thatthe QoL of patients with NFPA was damaged on the dimensions of general health, social function and role emotion.The dimension of physical painin patients with NFPA was better than that in general population, and there was no difference between other health dimensions. PMID- 27266492 TI - [Analysis of outcomes and learning curve of endoscopic transsphenoidal surgeries for 124 patients with pituitary adenomas]. AB - OBJECTIVE: To investigate the outcomes of the Endoscopic transsphenoidal surgery for patients with pituitary adenomas, analyze the learning curve and provide reference for future surgeries. METHODS: Retrospective analysis was carried out on 124 patients by endoscopic transsphenoidal surgery with a single neurosurgeon over a period spanning from January 2010 to January 2014 at Peking Union Medical College Hospital.The changes of endocrine and tumor imaging before and after surgery were analysed. Operative time and complication rates of one surgeon in the early period of learning curve were compared with that in later period. RESULTS: There were significant differences in Gross total resection (GTR) rate of pituitary adenomas with different sizes and different Knosp classifications (P<0.01, P<0.01). GTR rate of huge adenomas was significantly lower than that of macroadenoma and adenomas (P<0.05). GTR rate of Knosp 4 grade adenoma was significantly lower than that of Knosp 0-3 level (P<0.05). No significant difference in GTR among all types of functional pituitary adenomas and hormone levels after surgery was observed (P>0.05). In addition, no significant difference (P>0.05) in complications among different sizes, Knosp grade and type of pituitary adenomas was observed.GTR of Knosp 4 adenoma in later period of the learning curve was significantly higher than that in early period (P<0.05). Meanwhile the operative time was significantly lower than early period (P<0.05). CONCLUSIONS: Endoscopic transsphenoidal pituitary adenoma resection has the advantages of wider surgical field, higher GTR rate, less trauma, fewer complications and better life quality of patients.Through standardized learning, the GTR rate of the invasive pituitary adenomas can be improved. PMID- 27266494 TI - [Anterior retropharyngeal debridement combined with posterior atlantoaxial fusion for atlantoaxial Tuberculosis]. AB - OBJECTIVE: To evaluate the clinical efficacy of anterior debridement combined with posterior atlantoaxial fusion for atlantoaxial Tuberculosis. METHODS: From February 2005 to February 2013, 7 patients, 3 males and 4 females, with atlantoaxial Tuberculosis underwent anterior debridement combined with posterior atlantoaxial fusion in Department of Orthopedics Zhengzhou University People's Hospital were selected.In the preoperative and final follow-up, Japanese Orthopaedic Association score (JOA), neck disability index (NDI) and Frankel Classification were used to evaluate neurological function and calculate improvement rate.At final follow-up, clinical efficacy was evaluated by Odom's grade.Situation of internal fixation, fusion of upper cervical were assessed by X ray, CT scan and MRI scan. RESULTS: Bony fusion were achieved in 7 cases after operation in 12 months. Tuberculosis were reached clinical cure between 17 and 21 months. At follow The JOA score increased from (11.1+/-0.7) preoperatively to (15.3+/-0.5) in final follow-up(P<0.05), and the NDI decreased from (34.0+/-4.6) preoperatively to (10.1+/-1.3) in final follow-up (P<0.05). At last follow-up, according to Odom's standard, excellent were obtained in 5 cases, good 1 cases and ordinary 1 case. Frankel Classification of all cases improved from D class to E. CONCLUSIONS: The treatment of anterior retropharyngeal debridement combine with atlantoaxial fusion, and local anti-tuberculosis drug using intraoperative, not only could obtain reliable clinical efficacy, completly removal of lesions, but also obtain strong stability, which plays an important role in the treatment of atlantoaxial Tuberculosis. PMID- 27266493 TI - [The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China]. AB - OBJECTIVE: To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations. METHODS: In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015. RESULTS: As for in-hospital patients, mean age of study population was (48.6+/-11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84+/-0.53, and warfarin dosage of (2.82+/-0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85+/-1.23) mg/d and INR value was 1.82+/-0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study. CONCLUSIONS: INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy. PMID- 27266495 TI - [Clinical Analysis of Surgical treatment of long bone metastases]. AB - OBJECTIVE: To evaluate the safety and efficacy of microwave ablation combined with curettage in the treatment of long bone metastases. METHODS: From April 2010 to June 2015, 38 patients with long bone metastases were adopted, who all underwent microwave ablation combined with curettage with 40 lesions involved in Department of Orthopaedic Oncology, Beijing Jishuitan Hospital. There were 22 males and 16 females with an average age of 58.3 years (range from 32 to 83 years). Solitary metastases were found in 9 cases and multiple metastases in 29 patients. Primary malignancies included: 15 cases of lung cancer, 7 cases of renal carcinoma, 4 cases of breast cancer, 3 cases of liver cancer, 1 case of thyroid carcinoma, 1 case of endometrial carcinoma, 1 case of cervical carcinoma, 1 case of esophageal carcinoma and 6 cases of carcinoma of unknown primary. The operative sites included the femur (n=21), the humerus (n=12) and the tibia (n=7). There were 23 cases of pathologic fractures which included: 12 in femur, 10 in humerus and 1 in tibia. Curettage after in situ microwave ablation was performed in 40 lesions. Reconstructions were carried out in all lesions: bone cement filling alone in 1 lesion and bone cement filling with metal implants in the other 39 lesions. RESULTS: The mean follow-up was 6.9 months (range; 1-65 months). During the follow-up, 22 patients died and 16 patients were alive. The 6 month overall survival (OS) was 73.7%, and the 1-year and 2-year OS were 48.6% and 28.1% respectively. The postoperative survival time was 7.1 months on average (range 2-40 months) in the 22 patients who finally died. The occurrence of pathological fracture had a significant effect on the OS (chi(2)=5.606, P=0.018). The local recurrence rate was 10% (4/40), which occurred at 6.8 months after the operation on average (range 2-14 months). No complications occurred in the perioperative period, and there were no complications such as internal fixation failure or pathological fracture noticed during the follow-up period. The scores of VAS, KPS and ECOG were significantly improved after operation. The mean MSTS score was 22 points (range 17-28 points) in 33 evaluable locations and the rate of excellent and good was 72.7%. CONCLUSIONS: Microwave ablation combined with curettage appears to be a safe and effective approach in the surgical treatment of long bone metastases, which can relieve local pain and control the local development of bone metastases. PMID- 27266496 TI - [Investigation of renal corticomedullary differentiation with age-related change on non-contrast-enhanced MRI]. AB - OBJECTIVE: To evaluate the relationship between renal corticomedullary differentiation, renal cortical thickness and age-related changes with non contrast-enhanced steady-state free precession(SSFP) magnetic resonance imaging (MRI) and spatially selective inversion recovery(IR) pulse technology as well as its applied value . METHODS: A total of 76 healthy volunteers had been recruited from August 2014 to June 2015 in First Hospital of China Medical University.All volunteers were divided into three groups: 2-40 years old, 41-60 years old, 61-80 years old. All 76 volunteers underwent non-contrast-enhanced steady-state free precession(SSFP) 3.0 T MRI scan using variable inversion times (TIs)(TI=1 000, 1 100, 1 200, 1 300, 1 400, 1 500, 1 600, 1 700 ms). The renal corticomedullary differentiation was observed and the signal intensity of renal cortex and medulla were measured respectively as well in order to calculate renal corticomedullary contrast ratio. Besides, renal cortical thickness and renal size were measured. RESULTS: All 76 volunteers were successfully performed all the sequences of MRI scan, including 152 useful imaging of kidney in total. The renal corticomedullary differentiation was clearly shown in all subjects. There was negative correlation between the optimal inversion time(TI) and age(r=-0.65, P<0.01). Similarly, negative correlation was observed between renal corticomedullary contrast ratio and age(r=-0.35, P<0.01). The mean renal cortical thickness of all subjects was (5.33+/-0.71)mm and there were statistically significant difference among those different groups, which was negative-related with age(r=-0.79, P<0.01). There was no statistically significant difference between sexuality and renal cortical thickness.Additionally, renal cortical thickness had no statistically significant difference in both sides of kidneys. CONCLUSION: The renal corticomedullary differentiation is depicted clearly by means of non-contrast-enhanced steady state free precession MRI with spatially selective inversion recovery pulse technology. The optimal inversion time decreases along with the increase of age. In the meanwhile, the renal cortical thickness could be measured truthfully and accurately. PMID- 27266497 TI - [3.0 T MR diffusion tentor imaging in the differential diagnosis of breast mass lesions]. AB - OBJECTIVE: To investigate the differential diagnostic value of DTI parameters in breast mass lesions by comparing apparent diffusion coefficient (ADC), fractional aniotropy (FA) and maximum eigenvalue (lambda1)of normal glandular tissue, benign lesions and malignant lesions. METHODS: A total of 71 women patients with 74 mass lesions between December 2013 and October 2015 were enrolled from Beijing Chao Yang Hospital.MRI protocol included dynamic contrast-enhanced MRI (DCE-MRI)and diffusion tentor imaging(DTI) were executed.The ADC, lambda1 and FA of lesions and normal glandular tissue were calculated.The ADC, lambda1 and FA of lesions were compared by paired t test between the benign/malignant tumors and the contratlateral healthy breast tissue.ROC curve analysis was performed to compare diagnostic performance based on the area under the curve(AUC). The sensitivity and specificity of the DCE-MRI combined with ADC and DCE-MRI combined with lambda1 were calculated. RESULTS: The ADC, FA and lambda1 values of malignant lesions were (1.09+/-0.18)*10(-3) mm(2)/s, 0.22+/-0.02 and(0.97+/-0.19)*10(-3) mm(2)/s , these values of benign lesions were (1.52+/-0.19)*10(-3) mm(2)/s, 0.21+/-0.02 and(1.79+/-0.19)*10(-3) mm(2)/s, there were statistically significant differences (all P<0.05). Area under the curve of ADC, FA and lambda1 were 0.990, 0.605 and 0.978, respectively. The AUC of FA was lower than that of ADC and lambda1(P<0.01, <0.01), but there was no difference between the AUC of ADC and that of lambda1(P=0.131 6). The sensitivity DCE-MRI combined with ADC and DCE-MRI combined with lambda1 was 88.6% vs 97.1%(P=0.353 3), the specificity was 84.6% vs 97.4%(P=0.113 0). CONCLUSION: ADC and lambda1 is helpful to differentiate malignant from benign in mass lesions. PMID- 27266498 TI - [Differential diagnostic value of real-time tissue elastography and three dimensional ultrasound imaging in breast lumps]. AB - OBJECTIVE: To investigate the real-time tissue elastography and 3D contrast enhanced ultrasonography(CEUS) in breast lumps differential diagnostic value. METHODS: A total of 126 patients (180 lumps) with breast mass were retrospectively analyzed from December 2012 to December 2014 in Tumor Hospital Affiliated To Xinjiang Medical University.All patients were divided into three groups by using stratified random method.Each group was detected by real-time tissue elastography, 3D CEUS and two joint inspection.Each group of 42 cases (60 lumps) was confirmed by the pathological results as gold standard.Diagnostic sensitivity, specificity and coincidence rate of different methods were compared. RESULTS: The benign masses of ultrasound contrast showed the punctate, linear and nodular enhancement, and the border of enhancement was smooth.The malignant tumors were mainly dominated by uneven and high enhancement. There was no statistical difference in sensitivity, specificity and coincidence rate between elastography group and 3D CEUS group (64.7% vs 73.5%, 69.2% vs 76.9%, 66.7% vs 75.0%, all P>0.05). The sensitivity, specificity and coincidence rate of two joint inspection group were higher than those of elastography group and 3D CEUS group, the differences were statistically significant (97.1%, 92.3% and 98.3% , all P<0.05). CONCLUSION: 3D CEUS combined with real-time tissue elastography is of high value in the diagnosis of breast masses. PMID- 27266499 TI - [Value of DC and DRs in prediction of cardiovascular events in acute myocardial infarction patients]. AB - OBJECTIVE: To investigate the value of deceleration capacity of rate (DC) and heart rate deceleration runs(DRs) in predicting cardiovascular events in patient with acute myocardial infarction (AMI). METHODS: This study included 166 patients with AMI, who underwent ECG with sinus rhythm.These patients were followed-up for major adverse cardiac events (MACE). The receiver operating characteristic curve (ROC) was drawn to determine the best values for estimating the MACE. RESULTS: The mean follow-up time was (20.5+/-2.8) months, with 13 cases of cardiac death.There was statistically significant difference of DC, DRs and standard diviation of NN intervals(SDNN-24) between the death group and survival group.The area under the curve (AUC) of DC, DR4 and DR8 were larger than SDNN-24 (0.874, 0.804 vs 0.727). The values of DC, DR2, DR4 and root mean square of the successive differences(RMSSD) in the group of patients who underwent cardiac adverse events were smaller than the group of patients who didn't, and the AUC of DC was slightly higher than that of RMSSD. CONCLUSION: DC and DRs have important predictive value for cardiac death and MACE and can screen high-risk patients in patients with AMI. PMID- 27266500 TI - [Clinical data analysis of cardiovascular involvement in Behcet's disease]. AB - OBJECTIVE: To analysis the clinical features of cardiovascular involvement in Behcet's disease. METHODS: We reviewed 35 medical records of Behcet's disease with cardiovascular lesions in Anzhen Hospital, Capital Medical University from January 2002 to January 2014. 77.1% patients (27/35) were male. The mean (x+/-s) age when cardiovascular diseases occur was 37.19+/-10.4 years in male and 36.0+/ 8.6 years in female respectively. RESULTS: The clinical spectrum of cardiovascular abnormalities included valvular regurgitation (20, 57.1%), conduction system disturbances (10, 28.6%), intracardiac thrombosis(1, 2.9%), aneurysms of the arteries (13, 37.1%), artery stenosis or occlusion (5, 14.3%), pulmonary vascular diseases(3, 8.6%), venous thrombosis(4, 11.4%). Twenty patients had more than one of these lesions. Inflammatory indicators had no significantly difference between the above subgroups (P>0.05). Treatments included corticosteroids and immunosuppressive drugs, together with symptomatic treatments, intervention therapy and operation.Two inpatient died from multiple organ dysfunction syndrome and cardiac shock respectively. CONCLUSIONS: Cardiovascular involvement is a remarkable systemic lesion of Behcet's disease. Multi-subject cooperation is beneficial for the diagnosis and treatment of the disease. PMID- 27266502 TI - [Effect of mouse nerve growth factor on cognitive impairment in whole brain irradiation rats]. AB - OBJECTIVE: To investigate the positive effects of mouse nerve growth factor(mNGF) on cognitive impairment in whole brain irradiation rats. METHODS: Fifty-five male Sprague-Dawley rats were randomly divided into normal control group, mNGF treated group, saline treated group.mNGF treated group and saline treated group were cranial irradiated at a single dose of 12 Gy by X-ray.30 days after radiation each group were treated with correspondent drugs.60 days after radiation, Morris water maze experiment, EB leakage of the brain, and expressions of neuN, vWF, ZO 1 in hippocampus by immunofluorescence, and expressions of neuN, vWF, ZO-1, VEGF and GFAP in hippocampus by Western blot were tested and analyzed. RESULTS: The escape latencies: normal control group< mNGF treated group< saline treated group; the numbers of crossing hidden platform in these 3 groups were 3.00+/- 1.08, 1.50+/- 1.08, 0.38+/- 0.48 times (P<0.01). EB leakage of these 3 groups were 0.14+/-0.14, 0.66+/-0.20 and 1.36+/-0.27 MUg/g (P<0.05). In immunofluorescence, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group.In Western blot, expressions of neuN, vWF and ZO-1: normal control group> mNGF treated group> saline treated group, yet the expressions of VEGF and GFAP: normal control group< mNGF treated group< saline treated group. CONCLUSION: mNGF ameliorates cognitive impairment after whole brain irradiation. PMID- 27266501 TI - [Diagnosis of obstructive sleep apnea syndrome using pulse oximeter derived photoplethysmographic signals]. AB - OBJECTIVE: To evaluate the diagnosis value of photoplethysmography (PPG)-based device for detecting obstructive sleep apnea syndrome. METHODS: Patients who visited sleep medicine center in West China hospital from March 2014 to March 2015 with a main complain of snoring were selected into this study, and they were simultaneously monitored with the PPG-based device while undergoing polysomnography (PSG). Using PSG as"gold standard", the sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) as well as corresponding areas under the receiver operator curves for an apnea hypopnea index (AHI) >=5/h, >=15/h and >=30/h were calculated for PPG. RESULTS: Valid results were available for 93 subjects, among them there were 64 men and 29 women with a mean age of (44+/-13) years old.There were no significant difference between total sleep time, wake time after sleep onset, AHI and oxygen saturation derived by PPG and PSG.Positive correlation was found between PPG-derived and PSG derived AHI (r=0.945). For AHI>=5/h, >=15/h and >=30/h respectively according PSG, sensitivity was 93%, 88%, 92%, specificity was 79%, 93%, 95%, PPV was 95%, 97%, 96%, NPV 75%, 76%, 91% for PPG. The corresponding areas under the receiver operator characteristic curves were 0.981, 0.996 and 0.995 respectively. CONCLUSION: PPG-derived data is consistent with simultaneous in-lab PSG in the diagnosis of obstructive sleep apnea syndrome. PMID- 27266503 TI - [The influence of patatin-like phospholipase domain-containing protein 3 on palmitic acid-induced hepatocyte apoptosis]. AB - OBJECTIVE: To explore the influence of patatin-like phospholipase domain containing protein 3 (PNPLA3) on palmitic acid (PA)-induced hepatocyte apoptosis and its mechanism. METHODS: Human hepatocarcinoma cell line HepG2 cells were transfected with PNPLA3(WT)-pcDNA3.1 (PNPLA3(WT) group) and PNPLA3(I148M) pcDNA3.1 (PNPLA3(I148M) group) plasmids respectively to overexpress wild type or mutant type PNPLA3, and cells transfected with empty vector pcDNA3.1 (NC group) were set as control group.After 24 h PA incubation, Oil red staining was used to determine lipid deposition, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) was used to measure apoptosis.Western blot was used to detect the protein level of endoplasmic reticulum (ER) stress and associated apoptosis.Enzyme-linked immunosorbent assay (ELISA) was used to test lysolecithin (LPC) levels in the cellular supernatant. RESULTS: After 24 h PA incubation, there was no significant difference in lipid deposition among three groups.Compared to NC group, the cell apoptosis rates of PNPLA3(WT) and PNPLA3(I148M) groups were increased by 2 times and 3 times respectively.The levels of ER stress PRKR-like endoplasmic reticulum kinase (PERK) pathway associated proteins, immunoglobulin-binding protein (BIP), p-PERK, p-eIF2alpha, and ER stress associated apoptosis pathway proteins, CCAAT/enhancer binding homologous protein (CHOP), p53 upregulated modulator of apoptosis (PUMA), Bax, caspase-3 were higher, and were more significant in PNPLA3(I148M) group.The LPC level in the supernatant of PNPLA3(WT) and PNPLA3(I148M) groups were about 5 times and 1.5 times of NC group respectively after PA incubation. CONCLUSION: PNPLA3 may be involved in palmitic acid-induced apoptosis mediated by hepatocyte ER stress through regulating LPC metabolism. PMID- 27266504 TI - Construction of the Fused Pentacycle of Talatisamine via a Combination of Radical and Cationic Cyclizations. AB - The fused 6/7/5/6/6-membered (ABCDE) ring system of talatisamine was synthesized in 22 steps. After preparation of the AE-ring structure from 2 (ethoxycarbonyl)cyclohexanone, elaboration of the carboskeleton was realized by sequential additions of allyl magnesium bromide and the lithiated C-ring. The C11 bridgehead radical derived from the ACE-ring underwent the 7-endo cyclization with the enone moiety to form the B-ring in C10-stereoselective and C11 stereospecific manners. The 6-endo cyclization of the remaining D-ring was in turn attained by using the silyl enol ether as the nucleophile and the PhSeCl activated olefin as the electrophile. These radical and cationic cyclizations were demonstrated to be highly chemoselective, and they significantly contributed to streamlining the route to the intricately fused pentacycle of talatisamine. PMID- 27266505 TI - Non-perforation tension pneumoperitoneum resulting from primary non-aerobic bacterial peritonitis in a previously healthy middle-aged man: a case report. AB - BACKGROUND: Tension pneumoperitoneum is a rare surgical emergency in which free intraperitoneal gas accumulates under pressure. The known sources of free gas are perforated hollow viscera. We believe this is the first published case of a tension non-perforation pneumoperitoneum secondary to anaerobic gas production. This occurred in a background of primary non-aerobic bacterial peritonitis, which developed in an immunocompetent adult man. CASE PRESENTATION: A previously healthy 45-year-old Bulgarian man presented with a 3-week history of abdominal pain. He displayed signs of shock, peritonitis, and abdominal compartment syndrome. A plain abdominal X-ray showed the pathognomonic "saddlebag sign" with his liver displaced downwards and medially. An emergency laparotomy released pressurized gas, accompanied by 3100 mL of foamy pus. A sudden hemodynamic deterioration occurred soon after decompression. The sources of infection and tension pneumoperitoneum were not found. The peritoneal exudate sample did not recover aerobes. A laparostomy was created and three planned re-operations were performed. During the second re-laparotomy we placed an intraperitoneal silo and his abdomen was closed with skin sutures. Definitive fascial closure was achieved through separation of his two rectus muscles from their posterior sheaths. He was discharged in good health on the 25th postoperative day. CONCLUSIONS: Our case provides evidence supporting the theory that anaerobic infection may underlie the etiology of tension pneumoperitoneum. Prior to decompressive laparotomy the patient should receive an intravenous volume bolus to compensate for possible hypotension. If laparostomy leads to lateralization of the rectus muscles with a gap of 6 cm or less, the posterior part of the components separation technique is effective in achieving fascial closure. We present an original classification of tension pneumoperitoneum defining it as primary or secondary. PMID- 27266506 TI - Efficacy and safety of auricular point acupressure treatment for gastrointestinal dysfunction after laparoscopic cholecystectomy: study protocol for a randomized controlled trial. AB - BACKGROUND: Practitioners of traditional Chinese medicine know that auricular point acupressure (APP) using vaccaria seeds on the large intestine point (CO7) has a significant effect on postoperative gastrointestinal dysfunction. A standardized, clinical, research design will transform this clinical experience into scientific evidence, thus providing a basis to promote the wider use of this therapy. We aim to carry out a double-blind, randomized, controlled trial (RCT) to evaluate the efficacy and safety of APP treatment for gastrointestinal dysfunction after laparoscopic cholecystectomy. METHODS/DESIGN: This study is a randomized, double-blind, controlled, single-center, clinical, pilot trial. It has been designed according to the Consolidated Standards of Reporting Trials (CONSORT 2010) guidelines as well as the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). Study subjects are being selected from among hospitalized patients who have undergone laparoscopic cholecystectomy at the Department of Minimally Invasive Surgery of Tianjin Nankai Hospital. Qualified subjects will be assigned randomly either to the APP group or to the APP sham stimulation group on the basis of random numbers generated using SPSS 19.0. A specifically appointed investigator will be responsible for the randomization. The APP therapy (or sham stimulation) will be performed 6 h after surgery and every 12 h subsequently; six sessions will be conducted, each lasting 3 min. The first evaluation will be performed immediately before the first treatment (6 h after surgery) and, then, every 12 h for seven evaluations. The primary outcome is the time to first passage of flatus after surgery; the secondary outcome measures are abdominal distension, nausea, vomiting, time to first defecation, psychological status, and quality of life. DISCUSSION: This pilot trial is a standardized, scientific, clinical trial designed to evaluate the efficacy and safety of APP treatment-using vaccaria seeds on CO7-for gastrointestinal dysfunction after laparoscopic cholecystectomy. We aim to provide objective evidence to promote this therapy in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-15007643 . Registered on 14 December 2015. PMID- 27266507 TI - Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication. AB - BACKGROUND: Augmentation index, a marker of central wave reflection, is influenced by age, sex, height, blood pressure, heart rate, and arterial stiffness. However, the detailed haemodynamic determinants of augmentation index, and their relations, remain uncertain. We examined the association of augmentation index with vascular resistance and other haemodynamic and non haemodynamic factors. METHODS: Background information, laboratory values, and haemodynamics of 488 subjects (239 men, 249 women) without antihypertensive medication were obtained. Indices of central wave reflection, systemic vascular resistance, cardiac function, and pulse wave velocity were measured using continuous radial pulse wave analysis and whole-body impedance cardiography. RESULTS: In a regression model including only haemodynamic variables, augmentation index in males and female subjects, respectively, was associated with systemic vascular resistance (beta = 0.425, beta = 0.336), pulse wave velocity (beta = 0.409, beta = 0.400) (P < 0.001 for all), stroke volume (beta = 0.256, beta = 0.278) (P = 0.001 for both) and heart rate (beta = -0.150, beta = 0.156) (P = 0.049 and P = 0.036). When age, height, weight, smoking habits, and laboratory values were included in the regression model, the most significant explanatory variables for augmentation index in males and females, respectively, were age (beta = 0.577, beta = 0.557) and systemic vascular resistance (beta = 0.437, beta = 0.295) (P < 0.001 for all). In the final regression model, pulse wave velocity was not a significant explanatory variable for augmentation index, probably due to the high correlation of this variable with age (Spearman's correlation >=0.617). CONCLUSION: Augmentation index is strongly associated with systemic vascular resistance in addition to arterial stiffness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01742702 . PMID- 27266508 TI - Evaluation of rate law approximations in bottom-up kinetic models of metabolism. AB - BACKGROUND: The mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question. RESULTS: In this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction mass action rate law that removes the role of the enzyme from the reaction kinetics. We utilized in vivo data for the human red blood cell to compare the effect of rate law choices against the backdrop of physiological flux and concentration differences. We found that the Michaelis Menten rate law with measured enzyme parameters yields an excellent approximation of the full system dynamics, while other assumptions cause greater discrepancies in system dynamic behavior. However, iteratively replacing mechanistic rate laws with approximations resulted in a model that retains a high correlation with the true model behavior. Investigating this consistency, we determined that the order of magnitude differences among fluxes and concentrations in the network were greatly influential on the network dynamics. We further identified reaction features such as thermodynamic reversibility, high substrate concentration, and lack of allosteric regulation, which make certain reactions more suitable for rate law approximations. CONCLUSIONS: Overall, our work generally supports the use of approximate rate laws when building large scale kinetic models, due to the key role that physiologically meaningful flux and concentration ranges play in determining network dynamics. However, we also showed that detailed mechanistic models show a clear benefit in prediction accuracy when data is available. The work here should help to provide guidance to future kinetic modeling efforts on the choice of rate law and parameterization approaches. PMID- 27266509 TI - Prevalence of high-risk human papillomavirus and abnormal pap smears in female sex workers compared to the general population in Antwerp, Belgium. AB - BACKGROUND: Although female sex workers (FSWs) are a well-known high-risk group for Human Papillomavirus (HPV) infections, few tailored intervention programmes for HPV have been established worldwide. The lack of reliable data on the prevalence of HPV and related cervical lesions hampers the establishment of evidence-based intervention programmes. The objectives of this study were to describe the prevalence of high-risk Human Papillomavirus (hrHPV) infections and abnormal pap smears in FSWs compared to a control group in Antwerp, Belgium. METHODS: HPV genotyping and cytology data were analysed from routine Pap smear tests that were collected from both FSWs and the general population (1334 samples for each group) between June 2006 and June 2010. Within the laboratory database, all FSWs were matched 1:1 for age and testing date to determine the ORs of hrHPV genotypes, DNA and cytology outcome. RESULTS: The prevalence of hrHPV DNA in FSWs was 41.7 % compared to 19.8 % in the age-matched controls with an overall OR of 2.8 (95 % CI: 2.3-3.4). Significant differences were observed in all age groups, and the most significant differences were observed in the cohort under 21 years of age (prevalence of 64.4 % in FSWs versus 14.8 % in controls; OR 10.3 (95 % CI: 5.0-21.2). Significantly more cervical lesions were observed in FSWs, particularly in the 17- to 21-year old age group (OR for LSIL or HSIL: 10.3 (95 % CI: 3.2-33.8). In both groups, HPV 16 was the most prevalent at 12.1 and 6.6 % in the FSW and control groups, respectively. HPV 18 was the 8(th) and 7(th) most frequent genotype at 5.0 and 2.5 % in the FSW and control groups, respectively. CONCLUSIONS: FSWs have a significantly higher prevalence of hrHPV and more abnormal Pap smears than does the general population in Antwerp, Belgium. The hrHPV prevalence in FSWs is similar to that reported in the literature. The need for tailored intervention programmes should be investigated further. PMID- 27266510 TI - T-helper-associated cytokines expression by peripheral blood mononuclear cells in patients with polypoidal choroidal vasculopathy and age-related macular degeneration. AB - BACKGROUND: Immune responses play a key role in the pathogenesis and progression of polypoidal choroidal vasculopath (PCV) and age-related macular degeneration (AMD). In this study, we determined the Th cell-associated immune responses by measuring the cytokine expression of peripheral blood mononuclear cells (PBMC) in both PCV and neovascular AMD (nAMD) patients. METHODS: Twenty-seven nAMD patients, 33 PCV patients and a gender- and age-matched group of 18 healthy individuals were involved in this study. The Th-cell cytokine profiles including levels of interferon-gamma (INF-gamma), interleukin (IL)-17A and IL-4 in cultures of PBMCs were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: IFN-gamma,IL-17A and IL-4 production was significantly increased after stimulation with PHA. The levels of IFN-gamma and IL-4 in PHA-stimulated cultures were higher in PCV and nAMD patients than that in healthy controls (P = 0.038,P = 0.014), while no difference was found between PCV and nAMD (all P > 0.05). No significant difference in IL-17A level in PHA-stimulated cultures was found among PCV, nAMD and control groups (P > 0.05). CONCLUSIONS: These findings suggest that circulating IFN-gamma and IL-4 producing Th1 and Th2 cells may involve in the pathogenesis of PCV and nAMD. PCV may have the similar immune responses with nAMD. PMID- 27266511 TI - Proximity to mining industry and respiratory diseases in children in a community in Northern Chile: A cross-sectional study. AB - BACKGROUND: In a community in northern Chile, explosive procedures are used by two local industrial mines (gold, copper). We hypothesized that the prevalence of asthma and rhinoconjunctivitis in the community may be associated with air pollution emissions generated by the mines. METHODS: A cross-sectional study of 288 children (aged 6-15 years) was conducted in a community in northern Chile using a validated questionnaire in 2009. The proximity between each child's place of residence and the mines was assessed as indicator of exposure to mining related air pollutants. Logistic regression, semiparametric models and spatial Bayesian models with a parametric form for distance were used to calculate odds ratios and 95 % confidence intervals. RESULTS: The prevalence of asthma and rhinoconjunctivitis was 24 and 34 %, respectively. For rhinoconjunctivitis, the odds ratio for average distance between both mines and child's residence was 1.72 (95 % confidence interval 1.00, 3.04). The spatial Bayesian models suggested a considerable increase in the risk for respiratory diseases closer to the mines, and only beyond a minimum distance of more than 1800 m the health impact was considered to be negligible. CONCLUSION: The findings indicate that air pollution emissions related to industrial gold or copper mines mainly occurring in rural Chilean communities might increase the risk of respiratory diseases in children. PMID- 27266512 TI - Dirofilaria repens microfilariae from a human node fine-needle aspirate: a case report. AB - BACKGROUND: Human dirofilariosis is still a little known infection even in endemic areas. Dirofilariosis is zoonotic infection usually abortive in humans; instead, we report a very rare case (the 4th in the world), the first in Italy, in which at least two infective larvae became mature adults that mated and produced active microfilariae even though they did not reach peripheral blood. CASE PRESENTATION: A 30-year-old Italian woman presented with a transient oedematous swelling on the left abdominal wall with a creeping eruption followed by the occurrence of a subcutaneous nodular painless mass in the iliac region. One month later, a similar temporary swelling appeared on the contralateral inguinal region associated with intermittent joint discomfort in both knees. The patient had recently travelled abroad, therefore many possible diagnoses were to be ruled out. Routine laboratory investigations revealed eosinophilia. An ultrasound examination of the iliac swelling evidenced a well-defined cyst with a big filamentous formation in continuous movement. A fine-needle aspiration of the lesion was performed for parasitological, cytological and histological exams. The prompt microscopic examination of the aspired material showed the presence of numerous microfilariae that were initially morphologically attributed to Mansonella ozzardi. Subsequently, the revision of the Giemsa stained film and molecular analyses of the biological material, allowed to identify Dirofilaria repens as etiological agent of infection. CONCLUSIONS: We report of a case in whom microfilariae were detected in fine-needle aspirate of subcutaneous node, without evidence of microfilaraemia, and the infection failed to become fully patent. Therefore we confirm that complete development and fertilization of D. repens worms in human hosts may occur, at variance with what is commonly believed, that Dirofilaria worms cannot fully develop in humans. PMID- 27266513 TI - Alcohol consumption and lung cancer risk in never smokers. AB - OBJECTIVE: The main objective of this study is to analyse the role of alcohol consumption on lung cancer risk in people who have never smoked. METHODS: We conducted a systematic review of the scientific literature following the PRISMA statement. We searched Medline, EMBASE and CINAHL using different combinations of MeSH terms and free text. We included cohort studies, pooled cohort studies and case-control studies comprising at least 25 anatomopathologically-confirmed diagnoses of lung cancer cases, a sample size larger than 100 individuals and more than five years of follow-up for cohort studies. We excluded studies that did not specifically report results for never smokers. We developed a quality score to assess the quality of the included papers and we ultimately included 14 investigations with a heterogeneous design and methodology. RESULTS: Results for alcohol consumption and lung cancer risk in never smokers are inconclusive; however, several studies showed a dose-response pattern for total alcohol consumption and for spirits. Heterogeneous results were found for wine and beer. CONCLUSION: No clear effect is observed for alcohol consumption. Due to the limited evidence, no conclusion can be drawn for beer or wine consumption. There is little research available on the effect of alcohol on lung cancer risk for people who have never smoked, and more studies are urgently needed on this topic. PMID- 27266514 TI - Trans-fatty acid content of food products in Spain in 2015. AB - OBJECTIVE: To ascertain the content of trans-fatty acids (TFA) in food products in Spain in 2015 and assess trends in TFA content since 2010. METHODS: We analysed the fat content of 277 food products purchased in Spanish supermarkets in 2015 and calculated both the total fat and TFA content and the proportion of TFA to total fats. The results obtained in 2015 were compared to those yielded by a similar study in 2010. RESULTS: In 2015, the majority of food products studied had a TFA content of less than 0.2g/100g product, and a TFA/total fat ratio of less than 2%. No significant increases were found compared to 2010. Food groups with a higher TFA content were dairy products of possible natural origin. CONCLUSIONS: TFA content in Spain is low and has significantly fallen since 2010. PMID- 27266515 TI - [Influence of length of hospital stay on mortality after discharge in older patients with acute medical diseases]. AB - OBJECTIVE: To analyse whether hospital length of stay is associated with mortality at six months after discharge in the elderly. METHODS: An observational longitudinal study of patients surviving at hospital discharge. A binary logistic regression analysis was performed to study factors related to extended stay (> 12 days). The relationship between mortality at 6 months and length-of-stay quartiles was studied using a Cox regression analysis. RESULTS: 1180 patients were studied with a mean age of 86.6 years (standard deviation: 6.9). The median length of stay was 8 days (interquartile range: 5-12). Six-month mortality was 26.1%. After adjusting for age, gender, main diagnosis, comorbidity, albumin at admission, functional deterioration at admission and functional and mental status at discharge, hospital stay above the median was associated with mortality at 6 months: 9-12 days, HR=1.79, 95% CI: 1.01-3.14; and > 12 days, HR=2.04, 95% CI: 1.19-3.53. CONCLUSIONS: Prolonged hospital stay is an independent risk factor for mortality at 6 months after discharge. PMID- 27266516 TI - Accurate prediction of RNA-binding protein residues with two discriminative structural descriptors. AB - BACKGROUND: RNA-binding proteins participate in many important biological processes concerning RNA-mediated gene regulation, and several computational methods have been recently developed to predict the protein-RNA interactions of RNA-binding proteins. Newly developed discriminative descriptors will help to improve the prediction accuracy of these prediction methods and provide further meaningful information for researchers. RESULTS: In this work, we designed two structural features (residue electrostatic surface potential and triplet interface propensity) and according to the statistical and structural analysis of protein-RNA complexes, the two features were powerful for identifying RNA-binding protein residues. Using these two features and other excellent structure- and sequence-based features, a random forest classifier was constructed to predict RNA-binding residues. The area under the receiver operating characteristic curve (AUC) of five-fold cross-validation for our method on training set RBP195 was 0.900, and when applied to the test set RBP68, the prediction accuracy (ACC) was 0.868, and the F-score was 0.631. CONCLUSIONS: The good prediction performance of our method revealed that the two newly designed descriptors could be discriminative for inferring protein residues interacting with RNAs. To facilitate the use of our method, a web-server called RNAProSite, which implements the proposed method, was constructed and is freely available at http://lilab.ecust.edu.cn/NABind . PMID- 27266517 TI - Adjunctive use of essential oils following scaling and root planing -a randomized clinical trial. AB - BACKGROUND: Hitherto no study has been published on the effect of the adjunctive administration of essential oils following scaling and root planing (SRP). This study describes the effect of a mouthrinse consisting of essential oils (Cymbopogon flexuosus, Thymus zygis and Rosmarinus officinalis) following SRP by clinical and microbiological variables in patients with generalized moderate chronic periodontitis. METHODS: Forty-six patients (aged 40-65 years) with moderate chronic periodontitis were randomized in a double-blind study and rinsed their oral cavity following SRP with an essential oil mouthrinse (n = 23) or placebo (n = 23) for 14 days. Probing depth (PD), attachment level (AL), bleeding on probing (BOP) and modified sulcus bleeding index (SBI) were recorded at baseline and after 3 and 6 months. Subgingival plaque was taken for assessment of major bacteria associated with periodontitis. RESULTS: AL, PD, BOP and SBI were significantly improved in both groups after three (p < 0.001) and 6 months (p <= 0.015). AL improved significantly better in the test than in the control group after 3 and 6 months (p < 0.001), so did PD after three months in the tendency (p = 0.1). BOP improved better in the test group after 3 months (p = 0.065). Numbers of Treponema denticola (p = 0.044) and Fusobacterium nucleatum (p = 0.029) decreased more in the test than in the control group after 3 months, those of Tannerella forsythia after 6 months (p = 0.039). Prevotella micra (p < 0.001, p = 0.035) and Campylobacter rectus (p = 0.002 , p = 0.012) decreased significantly in both groups after 3 months. CONCLUSIONS: The adjunctive use of a mouthrinse containing essential oils following SRP has a positive effect on clinical variables and on bacterial levels in the subgingival biofilm. TRIAL REGISTRATION: 332-12-24092012, DRKS 00009387, German Clinical Trials Register, Freiburg i. Br., 16.09.2015. PMID- 27266519 TI - Effects of arbuscular mycorrhizae on tomato yield, nutrient uptake, water relations, and soil carbon dynamics under deficit irrigation in field conditions. AB - Plant strategies to cope with future droughts may be enhanced by associations between roots and soil microorganisms, including arbuscular mycorrhizal (AM) fungi. But how AM fungi affect crop growth and yield, together with plant physiology and soil carbon (C) dynamics, under water stress in actual field conditions is not well understood. The well-characterized mycorrhizal tomato (Solanum lycopersicum L.) genotype 76R (referred to as MYC+) and the mutant nonmycorrhizal tomato genotype rmc were grown in an organic farm with a deficit irrigation regime and control regime that replaced evapotranspiration. AM increased marketable tomato yields by ~25% in both irrigation regimes but did not affect shoot biomass. In both irrigation regimes, MYC+ plants had higher plant nitrogen (N) and phosphorus (P) concentrations (e.g. 5 and 24% higher N and P concentrations in leaves at fruit set, respectively), 8% higher stomatal conductance (gs), 7% higher photosynthetic rates (Pn), and greater fruit set. Stem water potential and leaf relative water content were similar in both genotypes within each irrigation regime. Three-fold higher rates of root sap exudation in detopped MYC+ plants suggest greater capacity for water uptake through osmotic driven flow, especially in the deficit irrigation regime in which root sap exudation in rmc was nearly absent. Soil with MYC+ plants also had slightly higher soil extractable organic C and microbial biomass C at anthesis but no changes in soil CO2 emissions, although the latter were 23% lower under deficit irrigation. This study provides novel, field-based evidence for how indigenous AM fungi increase crop yield and crop water use efficiency during a season-long deficit irrigation and thus play an important role in coping with increasingly limited water availability in the future. PMID- 27266520 TI - Projected climate change impacts upon dew yield in the Mediterranean basin. AB - Water scarcity is increasingly raising the need for non-conventional water resources, particularly in arid and semi-arid regions. In this context, atmospheric moisture can potentially be harvested in the form of dew, which is commonly disregarded from the water budget, although its impact may be significant when compared to rainfall during the dry season. In this study, a dew atlas for the Mediterranean region is presented illustrating dew yields using the yield data collected for the 2013 dry season. The results indicate that cumulative monthly dew yield in the region can exceed 2.8mm at the end of the dry season and 1.5mm during the driest months, compared to <1mm of rainfall during the same period in some areas. Dew yields were compared with potential evapotranspiration (PET) and actual evapotranspiration (ET) during summer months thus highlighting the role of dew to many native plants in the region. Furthermore, forecasted trends in temperature and relative humidity were used to estimate dew yields under future climatic scenarios. The results showed a 27% decline in dew yield during the critical summer months at the end of the century (2080). PMID- 27266518 TI - IL4 induces IL6-producing M2 macrophages associated to inhibition of neuroinflammation in vitro and in vivo. AB - BACKGROUND: Myeloid cells, such as macrophages and microglia, play a crucial role in neuroinflammation and have been recently identified as a novel therapeutic target, especially for chronic forms. The general aim would be to change the phenotype of myeloid cells from pro- to anti-inflammatory, favoring their tissue trophic and regenerative functions. Myeloid cells, however, display a number of functional phenotypes, not immediately identifiable as pro- or anti-inflammatory, and associated to ambiguous markers. METHODS: We employed in vitro assays to study macrophage polarization/differentiation in the presence of classical polarizing stimuli such as IFNgamma (pro-inflammatory) and IL4 (anti inflammatory). We induced neuroinflammation in mice by immunization with a myelin antigen and treated diseased mice with intracisternal delivery of an IL4 expressing lentiviral vector. We analyzed clinical, pathological, and immunological outcomes with a focus on myeloid cells. RESULTS: We found that IL6, usually considered a pro-inflammatory cytokine, was released in vitro by macrophages treated with the anti-inflammatory cytokine IL4. We show the existence of macrophages expressing IL6 along with classical anti-inflammatory markers such as CD206 and demonstrate that these cells are immunosuppressive in vitro. In neuroinflamed mice, we show that IL4 delivery in the central nervous system (CNS) is associated with clinical and pathological protection from disease, associated with increased IL6 expression in infiltrating macrophages. CONCLUSIONS: IL6 is known to mediate both pro- and anti-inflammatory effects, having two distinct ways to induce cell-signaling: either through the membrane bound receptor (anti-inflammatory) or through trans-signaling (pro-inflammatory). We show here that IL6-expressing macrophages are associated to protection from neuroinflammation, suggesting that IL6 anti-inflammatory properties prevail in the CNS, and calling for a general reconsideration of IL6 in macrophage polarization. PMID- 27266521 TI - Estimating adult mortality attributable to PM2.5 exposure in China with assimilated PM2.5 concentrations based on a ground monitoring network. AB - Estimates of mortality attributable to air pollution in China showed large differences among various studies, mainly arising from differences in exposure assessments and choice of the concentration-response function. The Chinese national monitoring network recently has included direct measurements of PM2.5 (particulates with aerodynamic diameter<=2.5MUm), providing a potentially more reliable exposure assessment. We estimated adult premature mortalities due to PM2.5 across China in 2013 and mortality benefits for scenarios in which China meets the World Health Organization (WHO) Air Quality Guidelines (AQG) and three interim targets (ITs) for PM2.5. Attributable adult mortalities were estimated with assimilated spatial PM2.5 concentrations across China based on direct PM2.5 measurements from 506 PM2.5 monitoring sites and a regional air quality model, and using the integrated exposure-response model. Our results show that in China, 83% of the population lived in areas where PM2.5 concentrations exceeded the Chinese Ambient Air Quality Standard of 35MUgm(-3). Premature mortalities attributed to PM2.5 nationwide were 1.37 million in total, and 0.69, 0.38, 0.13, and 0.17 million for stroke, ischemic heart disease, lung cancer, and chronic obstructive pulmonary disease, respectively. High population density areas exhibited the highest health risks attributed to air pollution. The mortality benefits will be 23%, 39%, 66%, and 83% of the total present premature mortalities (1.37 million mortalities) when PM2.5 concentrations in China meet the WHO IT-1, IT-2, IT-3, and AQG, respectively. Our study shows that integrating PM2.5 concentrations based on the national monitoring network with the regional air quality model provides an advanced exposure estimate method with potentials to further improve the accuracy for mortality estimate; much higher health benefits could be achieved if China adopted more stringent WHO guidelines for PM2.5. PMID- 27266522 TI - Polycyclic aromatic hydrocarbons and black carbon in intertidal sediments of China coastal zones: Concentration, ecological risk, source and their relationship. AB - Polycyclic aromatic hydrocarbons (PAHs) and black carbon (BC) have attracted many attentions, especially in the coastal environments. In this study, spatiotemporal distributions of PAHs and BC, and the correlations between BC and PAHs were investigated in the intertidal sediments of China coastal zones. BC in sediments was measured through dichromate oxidation (BCCr) and thermal oxidation (BCCTO). The concentrations of BCCr in the intertidal sediments ranged between 0.61 and 6.32mgg(-1), while BCCTO ranged between 0.57 and 4.76mgg(-1). Spatial variations of delta(13)C signatures in TOC and BC were observed, varying from -21.130/00 to 24.870/00 and from -23.530/00 to -16.780/00, respectively. PAH contents of sediments ranged from 195.9 to 4610.2ngg(-1) in winter and 98.2 to 2796.5ngg(-1) in summer, and significantly seasonal variations were observed at most sampling sites. However, the results of potential toxicity assessment indicated low ecological risk in the intertidal sediments of China coastal zones. Greater concentrations of PAHs measured in the sediments of estuarine environments indicated that rivers runoff may have been responsible for the higher PAH pollution levels in the intertidal sediments of China coastal zones. Pearson's correlation analysis suggested that pyrogenic compounds of PAH were significantly related to BC, due to that both BC and these compounds derived mainly from the combustion process of fossil fuels and biomass. Overall, increasing energy consumptions caused by anthropogenic activities can contribute more emissions of BC as well as PAHs and thus improve the importance of BC in indicating pyrogenic compounds of PAHs in the intertidal sediments of China coastal zones. PMID- 27266523 TI - Factors affecting population dynamics of leaf beetles in a subarctic region: The interplay between climate warming and pollution decline. AB - Understanding the mechanisms by which abiotic drivers, such as climate and pollution, influence population dynamics of animals is important for our ability to predict the population trajectories of individual species under different global change scenarios. We monitored four leaf beetle species (Coleoptera: Chrysomelidae) feeding on willows (Salix spp.) in 13 sites along a pollution gradient in subarctic forests of north-western Russia from 1993 to 2014. During a subset of years, we also measured the impacts of natural enemies and host plant quality on the performance of one of these species, Chrysomela lapponica. Spring and fall temperatures increased by 2.5-3 degrees C during the 21-year observation period, while emissions of sulfur dioxide and heavy metals from the nickel-copper smelter at Monchegorsk decreased fivefold. However, contrary to predictions of increasing herbivory with climate warming, and in spite of discovered increase in host plant quality with increase in temperatures, none of the beetle species became more abundant during the past 20years. No directional trends were observed in densities of either Phratora vitellinae or Plagiodera versicolora, whereas densities of both C. lapponica and Gonioctena pallida showed a simultaneous rapid 20-fold decline in the early 2000s, remaining at very low levels thereafter. Time series analysis and model selection indicated that these abrupt population declines were associated with decreases in aerial emissions from the smelter. Observed declines in the population densities of C. lapponica can be explained by increases in mortality from natural enemies due to the combined action of climate warming and declining pollution. This pattern suggests that at least in some tri trophic systems, top-down factors override bottom-up effects and govern the impacts of environmental changes on insect herbivores. PMID- 27266524 TI - Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development. AB - Chromatin-associated proteins are essential for the specification and maintenance of cell identity. They exert these functions through modulating and maintaining transcriptional patterns. To elucidate the functions of the Jmjd2 family of H3K9/H3K36 histone demethylases, we generated conditional Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c/Gasc1 single, double and triple knockout mouse embryonic stem cells (ESCs). We report that while individual Jmjd2 family members are dispensable for ESC maintenance and embryogenesis, combined deficiency for specifically Jmjd2a and Jmjd2c leads to early embryonic lethality and impaired ESC self-renewal, with spontaneous differentiation towards primitive endoderm under permissive culture conditions. We further show that Jmjd2a and Jmjd2c both localize to H3K4me3-positive promoters, where they have widespread and redundant roles in preventing accumulation of H3K9me3 and H3K36me3. Jmjd2 catalytic activity is required for ESC maintenance, and increased H3K9me3 levels in knockout ESCs compromise the expression of several Jmjd2a/c targets, including genes that are important for ESC self-renewal. Thus, continual removal of H3K9 promoter methylation by Jmjd2 demethylases represents a novel mechanism ensuring transcriptional competence and stability of the pluripotent cell identity. PMID- 27266526 TI - Discovery and Rational Design of Pteridin-7(8H)-one-Based Inhibitors Targeting FMS-like Tyrosine Kinase 3 (FLT3) and Its Mutants. AB - FLT3 has been validated as a therapeutic target for the treatment of acute myeloid leukemia (AML). In this paper, we describe for the first time, pteridin 7(8H)-one as a scaffold for potent FLT3 inhibitors derived from structural optimizations on irreversible EGFR inhibitors. The representative inhibitor (31) demonstrates single-digit nanomolar inhibition against FLT3 and subnanomolar KD for drug-resistance FLT3 mutants. In profiling of the in vitro tumor cell lines, it shows good selectivity against AML cells harboring FLT3-ITD mutations over other leukemia and solid tumor cell lines. The mechanism of action study illustrates that pteridin-7(8H)-one derivatives suppress the phosphorylation of FLT3 and its downstream pathways, thereby inducing G0/G1 cell cycle arrest and apoptosis in AML cells. In in vivo studies, 31 significantly suppresses the tumor growth in MV4-11 xenograft model. Overall, we provide a structurally distinct chemical scaffold with which to develop FLT3 mutants-selective inhibitors for AML treatment. PMID- 27266525 TI - Nucleosome eviction in mitosis assists condensin loading and chromosome condensation. AB - Condensins associate with DNA and shape mitotic chromosomes. Condensins are enriched nearby highly expressed genes during mitosis, but how this binding is achieved and what features associated with transcription attract condensins remain unclear. Here, we report that condensin accumulates at or in the immediate vicinity of nucleosome-depleted regions during fission yeast mitosis. Two transcriptional coactivators, the Gcn5 histone acetyltransferase and the RSC chromatin-remodelling complex, bind to promoters adjoining condensin-binding sites and locally evict nucleosomes to facilitate condensin binding and allow efficient mitotic chromosome condensation. The function of Gcn5 is closely linked to condensin positioning, since neither the localization of topoisomerase II nor that of the cohesin loader Mis4 is altered in gcn5 mutant cells. We propose that nucleosomes act as a barrier for the initial binding of condensin and that nucleosome-depleted regions formed at highly expressed genes by transcriptional coactivators constitute access points into chromosomes where condensin binds free genomic DNA. PMID- 27266527 TI - 3D Hierarchical Pt-Nitrogen-Doped-Graphene-Carbonized Commercially Available Sponge as a Superior Electrocatalyst for Low-Temperature Fuel Cells. AB - Three-dimensional hierarchical nitrogen-doped graphene (3D-NG) frameworks were successfully fabricated through a feasible solution dip-coating method with commercially available sponges as the initial backbone. A spongy template can help hinder the graphene plates restacking in the period of the annealing process. The Pt/3D-NG catalyst was synthesized employing a polyol reduction process. The resultant Pt/3D-NG exhibits 2.3 times higher activity for methanol electro-oxidation along with the improvement in stability as compared with Pt/G owing to their favorable features including large specific surface area, high pore volume, high N doping level, and the homogeneous dispersion of Pt nanoparticles. Besides, Pt/3D-NG also presents high oxygen reduction reaction (ORR) performance in acid media when compared with Pt/3D-G and Pt/G. This work raises a valid solution for the fabrication of 3D functional freestanding graphene-based composites for a variety of applications in fuel cell catalysis, energy storage, and conversion. PMID- 27266528 TI - Autosomal dominant polycystic kidney disease in children. PMID- 27266529 TI - Platelets activation is associated with elevated plasma mitochondrial DNA during cardiopulmonary bypass. AB - BACKGROUND: Mitochondrial DNA (mtDNA) was reported as a pro-inflammatory agent. In our previous study, elevation of plasma mtDNA was revealed after cardiac surgery with cardiopulmonary bypass (CPB). Platelets were activated during the cardiac surgery and recent study revealed its ability to release mtDNA. Our present study postulated that the elevated plasma mtDNA comes from activated platelets, which plays a critical role in post-CPB inflammatory responses. METHODS: Sixty-eight patients who underwent coronary artery bypass graft (CABG) with CPB were enrolled in our study. Blood samples were collected before induction of anaesthesia (T1), at the end of CPB (T2), 12 h post-CPB (T3), 24 h post-CPB (T4), 48 h post-CPB (T5) and 72 h post-CPB (T6). Blood samples were analyzed for the routine blood test and prepared for plasma isolation. MtDNA concentration was measured by rt-PCR, and TNF-alpha and IL-6 were examined by specific ELISA kits. Subgroup study was analyzed by activation levels of platelet. Basic information, mtDNA level, TNF-alpha level and IL-6 level were all carefully studied in each quartile. RESULTS: Activation level of platelets increased and peaked at T2, which decreased gradually from T3 to T6 (P < 0.05). MtDNA increased after CPB, peaked at T3, and then backed from T4 to T6 (P < 0.05). Bivariate correlation between peak activation level of platelets and peak plasma mtDNA level showed a positive correlation between these two parameters (r = 0.683, P < 0.0001). Both TNF-alpha and IL-6 showed similar patterns as mtDNA, with an increase from T1 to T3 and a decrease from T4 to T6 (P < 0.05). Subgroup analysis further demonstrated that patients with higher activation levels of PLT had higher plasma mtDNA levels and inflammatory level (P < 0.05). CONCLUSIONS: Our study revealed the dynamic changes of activation level of platelets and identified the interesting association between platelets activation and plasma mtDNA, suggesting a novel potential mechanism of activated platelets-induced post CPB inflammatory responses. PMID- 27266531 TI - Effects of Rho Kinase Inhibitors on Intraocular Pressure and Aqueous Humor Dynamics in Nonhuman Primates and Rabbits. AB - PURPOSE: This study examines the effects of 2 Rho kinase inhibitors on intraocular pressure (IOP) and aqueous humor dynamics. METHODS: IOPs of New Zealand albino rabbits with ocular normotension and cynomolgus macaques (nonhuman primate, NHP) with chronic unilateral laser-induced glaucoma were measured at baseline and periodically after a 9 a.m. dose of H-1152, Y-27632, or vehicle. In a separate group of NHPs, aqueous flow, outflow facility, uveoscleral outflow, and IOP were determined after treatment with Y-27632 or vehicle control. RESULTS: Decreases in IOP were found in rabbits (n = 5) at 6 h after one dose of 2% Y 27632 (29%, P = 0.0002) or 1% H-1152 (35%, P = 0.0001), and in hypertensive eyes of NHPs (n = 7-9) at 3 h after one dose of 2% Y-27632 (35%, P = 0.005) or 1% H 1152 (51%, P = 0.0003). With 2 doses of 1% Y-27632 or vehicle in NHP hypertensive eyes (n = 12), significant drug effects were IOP reduction of 28% (P = 0.05) at 2.5 h after the second dose and increases in aqueous flow (36%; P = 0.013), uveoscleral outflow (59%, P = 0.008), and outflow facility (40%; P = 0.01). In normotensive eyes of the same animals, aqueous flow increased by 21% (P = 0.03). No significant change was found in any of the other parameters. CONCLUSIONS: Y 27632 and H-1152 lower IOP in rabbits and hypertensive eyes of NHPs for at least 6 h after single doses. The Y-27632 effect on IOP in hypertensive NHP eyes is caused by increases in outflow facility and uveoscleral outflow. An increase in aqueous humor formation attenuates but does not prevent an IOP decrease. PMID- 27266530 TI - Exploring the psychological morbidity of waiting for sinus surgery using a mixed methods approach. AB - BACKGROUND: Patients with chronic rhinosinusitis (CRS) often have to endure significant wait times for endoscopic sinus surgery (ESS). The pyschiatric impact of placement on a waitlist for ESS has not been explored. METHODS: Questionnaires measuring CRS symptom severity and health-related anxiety and stress (SNOT-22, HADS, WPAI-GH) were sent to patients diagnosed with CRS and currently on a waitlist for ESS. Fifteen representative waitlisted patients participated in one on-one semi-structured interviews discussing their experience with their wait for ESS. A deductive thematic analysis was used to interpret the interview data using a quantitative driven mixed methods analysis. RESULTS: Participants waiting for ESS reported worsening clinical symptomatology during their waiting period. Participants reported waitlist and CRS impact on both work and social aspects of their lives. The HADS scale showed no overall significant level of depression or anxiety in the HADS screening questionnaire. The qualitative data describe the effects of the symptom burden of CRS. CONCLUSIONS: Patients waitlisted for ESS did not demonstrate any significant level of psychiatric distress, however variability exists. The qualitative arm of this study elucidates how patients cope with their wait. PMID- 27266533 TI - Impact of Repeated Questioning on Interviewers: Learning From a Forensic Interview Training Project. AB - Forensic interviewers have a difficult job with high risk for career burnout and secondary trauma. Few studies have addressed how new forensic interviewers or trainees experience repeated questioning and multiple interviews. This study simulated the process of training new forensic interviewers through the creation of two interview videos in which social work graduate students participated as actors portraying the roles of interviewer and child. These films served as instructional aids preparing graduate social work students for professional child welfare roles while promoting research-based approaches to interviewing children about sexual abuse allegations. Qualitative data from two cohorts of student actors were collected to analyze interviewers' perspectives on repeated questioning and interviews in child sexual abuse cases. Two themes were extracted from the subjects' experiences: "It is emotionally taxing" and "Navigating the interviewer role is unexpectedly complex." Exposure to repeated questions and multiple interviews affected the performance and confidence of the interviewers. PMID- 27266532 TI - Chemopreventive Agents Attenuate Rapid Inhibition of Gap Junctional Intercellular Communication Induced by Environmental Toxicants. AB - Altered gap junctional intercellular communication (GJIC) has been associated with chemical carcinogenesis, where both chemical tumor promoters and chemopreventive agents (CPAs) are known to conversely modulate GJIC. The aim of this study was to investigate whether attenuation of chemically inhibited GJIC represents a common outcome induced by different CPAs, which could be effectively evaluated using in vitro methods. Rat liver epithelial cells WB-F344 were pretreated with a CPA for either 30 min or 24 h, and then exposed to GJIC inhibiting concentration of a selected tumor promoter or environmental toxicant [12-O-tetradecanoylphorbol-13-acetate (TPA), lindane, fluoranthene, 1,1,1 trichloro-2,2-bis(4-chlorophenyl)ethane (DDT), perfluorooctanoic acid (PFOA), or pentachlorophenol]. Out of nine CPAs tested, quercetin and silibinin elicited the most pronounced effects, preventing the dysregulation of GJIC by all the GJIC inhibitors, but DDT. Metformin and curcumin attenuated the effects of three GJIC inhibitors, whereas the other CPAs prevented the effects of two (diallyl sulfide, emodin) or one (indole-3-carbinol, thymoquinone) GJIC inhibitor. Significant attenuation of chemically induced inhibition of GJIC was observed in 27 (50%) out of 54 possible combinations of nine CPAs and six GJIC inhibitors. Our data demonstrate that in vitro evaluation of GJIC can be used as an effective screening tool for identification of chemicals with potential chemopreventive activity. PMID- 27266534 TI - Investigative Interviewing of Aboriginal Children in Cases of Suspected Sexual Abuse. AB - This study examined the investigative interviewing of Australian Aboriginal children in cases of alleged sexual abuse, with a focus on three commonly included components of interview protocols: ground rules, practice narrative, and substantive phase. Analysis of 70 field transcripts revealed that the overall delivery and practice of ground rules at the beginning of the interview was positively associated with the spontaneous usage of rules in children's narratives of abuse. When specifically examining the "don't know" rule, however, only practice had an effect of children's usage of the rule (as opposed to simple delivery or no delivery at all). Children spoke more words overall, and interviewers used more open-ended prompts during the substantive phase when the interviews contained a practice narrative. Children most often disclosed sexual abuse in response to an open-ended prompt; however, they produced the most words in response to suggestive prompts. This article concludes with a discussion of the effectiveness of ground rules, practice narratives, and questioning with Aboriginal children. PMID- 27266535 TI - The Continuum of Disclosure: Exploring Factors Predicting Tentative Disclosure of Child Sexual Abuse Allegations During Forensic Interviews and the Implications for Practice, Policy, and Future Research. AB - When a child sexual abuse investigation ensues, many children do not disclose readily to professionals. Defining disclosure beyond the disclosure versus nondisclosure dichotomy is essential, yet little research exists on factors associated with a continuum of disclosure, including active and tentative disclosure. Through the coding of 196 forensic interviews using content analysis and subsequent regression analysis, findings suggest that children of color, children abused by adults, unintentional initial disclosure, and those lacking family support were more likely to tentatively disclose in this study. Implications include a need to understand tentative disclosure as part of a normal continuum of disclosure within court proceedings and investigations of abuse allegations. PMID- 27266536 TI - Caregiver Needs Following Disclosure of Child Sexual Abuse. AB - Caregiver support is vital in improving outcomes for child sexual abuse victims; however, the disclosure can significantly affect caregivers, thus impacting their ability to meet their children's needs. To maximize the support from caregivers, their own needs following disclosure need to be met. This study investigated the impact of child sexual abuse disclosure and associated needs as identified by caregivers. Sixty needs assessment forms were collected from families who accessed a parenting support pilot program run in New Zealand. These forms were completed by nonoffending caregivers during an assessment session with their counselor and consisted of both open-ended and Likert scale questions focusing on both the needs of the child and the family. Caregivers identified a range of impacts of the disclosure on their children, themselves, and other families members and the related support that may be needed. In particular, caregivers identified that they needed support with child behavior management and with their own coping. The findings suggest that interventions with caregivers following disclosure of child sexual abuse may be a valuable adjunct to therapy provided directly to the child. PMID- 27266537 TI - Gender Differences in Sexually Abused Children and Adolescents: A Multicenter Study in Turkey. AB - The purpose of this study was to examine gender-based differences in abuse related characteristics and post-abuse psychiatric disorders among sexually abused children and adolescents. The researchers retrospectively examined files, judicial reports, and social examination reports of 1,250 sexually abused youth cases. Results showed that boys were more often victimized by penetration, force, and physical violence. Incidence of sexual abuse by family members, familiar persons, and multiple persons was higher among girls. In addition, a higher rate of major depressive disorder as well as alcohol consumption and cigarette smoking were found in sexually abused girls. No difference was observed between boys and girls in terms of post-traumatic stress disorder, conduct disorder, and other mental disorders. Intellectual disability was more frequent in boys. PMID- 27266538 TI - Contributions of Child Sexual Abuse, Self-Blame, Posttraumatic Stress Symptoms, and Alcohol Use to Women's Risk for Forcible and Substance-Facilitated Sexual Assault. AB - Child sexual abuse and adult sexual assault have been linked to increased self blame, posttraumatic stress symptoms, and alcohol use. The current study aims to examine (a) whether these constructs explain women's risk for later adult sexual assault and revictimization, (b) whether such factors differentially confer risk for specific types of adult sexual assault (i.e., substance-facilitated and forcible), and (c) if self-blame confers risk indirectly through other risk factors. Multiple types of self-blame, posttraumatic stress, and alcohol use were examined among 929 female college students as serial mediators of the relationship between child sexual abuse and adult sexual assault and as risk factors for sexual revictimization among child sexual abuse survivors. In the model predicting risk for substance-facilitated adult sexual assault, child sexual abuse indirectly predicted greater risk for substance-facilitated adult sexual assault mediated through two separate paths: global blame-to-posttraumatic stress and global blame-to-alcohol use. In the model predicting risk for forcible adult sexual assault, child sexual abuse directly predicted greater risk for forcible adult sexual assault, and this relation was mediated by the global blame to-posttraumatic-stress path. Among child sexual abuse survivors, child sexual abuse specific characterological and behavioral self-blame directly predicted greater risk for forcible and substance-facilitated revictimization, but the pathways were not mediated by posttraumatic stress or alcohol use. Results emphasize the importance of assessing different types of self-blame in predicting posttraumatic stress symptoms as well as examining risk for sexual victimization and revictimization. Findings did not support hypotheses that increased posttraumatic stress would predict increased alcohol use but did indicate that heightened self-blame is consistently associated with heightened posttraumatic stress and that heightened global self-blame predicts increased alcohol use. Implications for future research and intervention are discussed. PMID- 27266539 TI - Maladaptive Schemas as Mediators in the Relationship Between Child Sexual Abuse and Displaced Aggression. AB - Child sexual abuse is one of the most serious forms of abuse due to the psychological consequences that persist even into adulthood. Expressions of anger among child sexual abuse survivors remain common even years after the event. While child sexual abuse has been extensively studied, the expression of displaced aggression has been studied less. Some factors, such as the maladaptive early schemas, might account for this deficiency. The objective of this study was to analyze the relationships between child sexual abuse, displaced aggression, and these schemas according to gender and determine if these early schemas mediate the relationship between child sexual abuse and displaced aggression. A total of 168 Spanish subjects who were victims of child sexual abuse completed measures of childhood trauma, displaced aggression, and early maladaptive schemas. The results depict the relationship between child sexual abuse, displaced aggression, and early maladaptive schemas. Women scored higher than men in child sexual abuse, emotional abuse, disconnection or rejection and impaired autonomy. Mediational analysis found a significant mediation effect of disconnection or rejection on the relationship between child sexual abuse and displaced aggression; however, impaired autonomy did not mediate significantly. PMID- 27266540 TI - Attitudes Toward Juvenile Sex Offender Legislation: The Influence of Case Specific Information. AB - This study examined attitudes toward the application of adult sex offender legislation to juvenile sex offenders. Participants were randomly assigned to one of nine conditions. In the generic condition, the participants were asked to envision a generic juvenile sex offender, whereas in the manipulated conditions, participants read a vignette with three manipulated variables: offense type, victim age, and victim gender. Afterward, all participants (n = 978) completed questionnaires assessing perceptions of juvenile sex offenders and juvenile sex offender legislation. Overall, participants in the generic juvenile sex offender condition rated the perpetrator as more dangerous and more likely to reoffend than participants in the experimental conditions. Moreover, participants in the generic juvenile sex offender condition were more likely to endorse more punitive punishments and viewed perpetrators as "superpredators." When examining differences between the experimental conditions, participants reading vignettes with younger victims and male victims as well as vignettes with contact offenses were more likely to view the perpetrator as dangerous, likely to recidivate, as a "superpredator," and deserving of more punitive punishments. Implications for public policy as well as future research directions are discussed. PMID- 27266541 TI - Monogenic mutations associated with IgA deficiency. AB - INTRODUCTION: For twenty years, two paradigms have been considered as the main genetic contributors to immunoglobulin A deficiency, including cytogenetic defects involving large chromosomal aberrations and an association with the human major histocompatibility complex (MHC) locus. However, an overview of recent studies suggests a role for several monogenic disorders in the development of this disease. Areas covered: This review examines the concept of monogenic disorders for patients with IgA deficiency in order to identify the underlying pathogenic mechanism(s). Expert commentary: A clinical/immunologic workup followed by targeted gene mutation analysis has been proposed for an approach to IgA deficient patients. PMID- 27266542 TI - The impact of self-efficacy, expectations, and readiness on hearing aid outcomes. AB - OBJECTIVE: To examine the impact of self-efficacy and expectations for hearing aids, and readiness to improve hearing, on hearing aid outcome measures in first time adult hearing aid users Design: A prospective, single centre design. Predictor variables measured at the hearing assessment included measures of self efficacy, expectations and readiness to improve hearing. Outcome measures obtained at six-week follow-up were the Glasgow Hearing Aid Benefit Profile and Satisfaction with Amplification in Daily Life. STUDY SAMPLE: A sample of 30 first time adult hearing aid users were recruited through a public-sector funded audiology clinic. RESULTS: When measured prior to hearing aid fitting, self efficacy for hearing aids predicted satisfaction with hearing aids but was not related to other hearing aid outcomes. Expectations of hearing aids, in particular positive expectations, and readiness to improve hearing predicted outcomes for hearing aid satisfaction and benefit, although not hearing aid use. Hearing sensitivity was not correlated with hearing aid outcomes. CONCLUSIONS: These results suggest that assessment of expectations of hearing aids, and readiness to improve hearing, may be useful to help identify individuals attending audiology clinics who would most likely benefit from hearing aid provision. PMID- 27266543 TI - HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine. AB - INTRODUCTION: Although current antiretroviral therapy (ART) has transformed HIV infection into a chronic, manageable disease, ART does not cure HIV infection. Furthermore, the majority of the world's infected individuals live in resource limited countries in which access to ART is limited. Thus, the development of an effective therapeutic HIV vaccine would be an invaluable treatment alternative. AREAS COVERED: Developed by the late Dr. Jonas Salk, HIV-1 Immunogen (Remune(r)) is a candidate therapeutic vaccine that has been studied in thousands of HIV infected individuals in more than a dozen clinical trials during almost three decades. This Drug Evaluation, which summarizes the results of these trials that have shown the vaccine to be safe and immunogenic, also discusses the contradictory and controversial conclusions drawn from the phases 2, 2/3 and 3 trials that assessed the clinical efficacy of this vaccine. EXPERT OPINION: Given the lack of unequivocal clinical benefits of HIV-1 Immunogen despite almost 30 years of extensive testing, it does not appear, in our view, that this vaccine is a clinically effective immunotherapy. However, inclusion of this vaccine in the newly proposed 'Kick/Shock and Kill' strategy for HIV eradication, or use as a prophylactic vaccine, could be considered for future trials. PMID- 27266544 TI - Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. METHODS: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. RESULTS: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. CONCLUSION: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. ADVANCES IN KNOWLEDGE: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID- 27266545 TI - Economic analysis of ALK testing and crizotinib therapy for advanced non-small cell lung cancer. AB - AIM: The economic outcome of crizotinib in advanced non-small-cell lung cancer harboring anaplastic lymphoma kinase rearrangement would be investigated. MATERIALS & METHODS: Based on a mathematical model, the economic outcome of three techniques for testing ALK gene rearrangement combing with crizotinib would be evaluated and compared with traditional regimen. The impact of the crizotinib patient assistance program (PAP) was assessed. RESULTS: Ventana immunohistochemistry, quantitative real-time reverse transcription-polymerase chain reaction and IHC testing plus fluorescent in situ hybridization confirmation for anaplastic lymphoma kinase testing following crizotinib treatment leaded to the incremental cost-effectiveness ratios of US$16,820 and US$223,242, US$24,424 and US$223,271, and US$16,850 and US$254,668 per quality adjusted life-year gained with and without PAP, respectively. CONCLUSION: Gene guided crizotinib therapy might be a cost-effective alternative comparing with the traditional regimen in the PAP setting. PMID- 27266546 TI - From the Editor. PMID- 27266557 TI - Improving combination antiretroviral therapy by targeting HIV-1 gene transcription. AB - INTRODUCTION: Combination Antiretroviral Therapy (cART) has not allowed the cure of HIV. The main obstacle to HIV eradication is the existence of quiescent reservoirs. Several other limitations of cART have been described, such as strict life-long treatment and high costs, restricting it to Western countries, as well as the development of multidrug resistance. Given these limitations and the impetus to find a cure, the development of new treatments is necessary. Areas covered: In this review, we discuss the current status of several efficient molecules able to suppress HIV gene transcription, including NF-kB and Tat inhibitors. We also assess the potential of new proteins belonging to the intriguing DING family, which have been reported to have potential anti-HIV-1 activity by inhibiting HIV gene transcription. Expert opinion: Targeting HIV-1 gene transcription is an alternative approach, which could overcome cART-related issues, such as the emergence of multidrug resistance. Improving cART will rely on the identification and characterization of new actors inhibiting HIV-1 transcription. Combining such efforts with the use of new technologies, the development of new models for preclinical studies, and improvement in drug delivery will considerably reduce drug toxicity and thus increase patient adherence. PMID- 27266559 TI - The Decade in Clinical Thyroid Disease: An Analysis of Published Literature. AB - BACKGROUND: The purpose of this study was to assess the current status of the clinical thyroidology literature using bibliographic analysis. METHODS: The subject "clinical thyroidology" was divided into six broad topics: iodine deficiency/iodine nutrition, hypothyroidism, hyperthyroidism/thyrotoxicosis, thyroiditis/autoimmune thyroid disease, thyroid nodules/multinodular goiter, and thyroid cancer. Using Scopus, an online bibliographic searching tool, this study sought to examine the trends in the publication of clinical thyroid disease related research articles over the decade from 2006 through the end of 2015. Citation counts were also retrieved for individual research papers in order to find papers that might have had a bigger impact on clinical practice. Review articles, guidelines, and editorials were excluded. RESULTS: A total of 19,055 articles were published in the broad area of clinical thyroid disease. The largest proportion was in the topic of thyroid cancer, accounting for >30% of the total. The numbers of papers published annually on thyroid nodules and thyroid cancer increased progressively over the decade. The largest proportion of clinical thyroid publications emanated from the United States, and the majority of papers were published in subspecialty journals. Within each clinical thyroid topic, the most highly cited papers published from 2006 to 2015 were identified, and outliers-that is, papers that had been cited far more often that others in the topic-were also identified. The most highly cited paper in all of clinical thyroidology was a 2006 study describing the increase in thyroid cancer incidence in the United States (JAMA 295:2164-2167). Most of the highly cited clinical papers were case series or cohort studies, rather than randomized controlled trials. CONCLUSIONS: The number of papers in clinical thyroid disease is expanding rapidly, with >1000 papers published annually over the last decade. Research papers on thyroid nodules and cancer accounted for 51% of all clinical thyroid disease-related papers. More randomized controlled trials have been published in the last few years, portending a bright future for clinical thyroidology. PMID- 27266558 TI - Evaluation of Breast Lipid Composition in Patients with Benign Tissue and Cancer by Using Multiple Gradient-Echo MR Imaging. AB - Purpose To demonstrate the feasibility of the use of a rapid, noninvasive, in vivo imaging method to measure fatty acid fractions of breast adipose tissue during diagnostic breast magnetic resonance (MR) examinations and to investigate associations between fatty acid fractions in breast adipose tissue and breast cancer status by using this method. Materials and Methods The institutional review board approved this retrospective HIPAA-compliant study and informed consent was waived. Between July 2013 and September 2014, multiple-echo three dimensional gradient-echo data were acquired for 89 women. Spectra were generated and used to estimate fractions of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) in the breast adipose tissue. Analysis of covariance and exact Mann-Whitney tests were used to compare groups and the Spearman rank correlation coefficient was used to characterize the association of each imaging measure with each attribute. Results For postmenopausal women, MUFA was lower (0.38 +/- 0.06 vs 0.46 +/- 0.10; P < .05) and SFA was higher (0.31 +/- 0.07 vs 0.19 +/- 0.11; P < .05) for women with invasive ductal carcinoma than for those with benign tissue. No correlation was found between body mass index (BMI) and fatty acid fractions in breast adipose tissue. In women with benign tissue, postmenopausal women had a higher PUFA (0.35 +/- 0.06 vs 0.27 +/- 0.05; P < .01) and lower SFA (0.19 +/- 0.11 vs 0.30 +/- 0.12; P < .05) than premenopausal women. Conclusion There is a possible link between the presence of invasive ductal carcinoma and fatty acid fractions in breast adipose tissue for postmenopausal women in whom BMI values are not correlated with the fatty acid fractions. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 27266560 TI - The roots of Salvia rhytidea: a rich source of biologically active diterpenoids. AB - Sahandinone (1), 12-deoxysalvipisone (2), miltirone (3), 7alpha-acetoxyroyleanone (4), and labda-7,14-dien-13-ol (5) were isolated from the roots of Salvia rhytidea Benth. (Lamiaceae). Their structures were elucidated by a combination of spectroscopic analyses including EIMS and NMR. The 13C NMR spectroscopic data were revised for the quaternary carbons of both 1 and 3 with the help of HMBC spectra in respect to the spectral data previously reported in the literature. Compounds 1 and 3, two very potent anticancer agents, were isolated in high yields from the roots of the plant. The biological activities of the plants' constituents were reported in the literature as antimicrobial, cytotoxic and antimalarial are discussed in this article. PMID- 27266563 TI - Test-retest, retest, and retest: Growth curve models of repeat testing with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). AB - Computerized neuropsychological testing has become an important tool in the identification and management of sports-related concussions; however, the psychometric effect of repeat testing has not been studied extensively beyond test-retest statistics. The current study analyzed data from Division I collegiate athletes who completed Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baseline assessments at four sequential time points that varied over the course of their athletic careers. Administrations were part of a larger National Institutes of Health (NIH) study. Growth curve modeling showed that the two memory composite scores increased significantly with successive administrations: Change in Verbal Memory was best represented with a quadratic model, while a linear model best fit Visual Memory. Visual Motor Speed and Reaction Time composites showed no significant linear or quadratic growth. The results demonstrate the effect of repeated test administrations for memory composite scores, while speed composites were not significantly impacted by repeat testing. Acceptable test-retest reliability was demonstrated for all four composites as well. PMID- 27266564 TI - Oxidative stress and altered expression of peroxiredoxin genes family (PRDXS) and sulfiredoxin-1 (SRXN1) in human lung tissue following exposure to sulfur mustard. AB - BACKGROUND: Sulfur mustard (SM) is a potent and mutagenic agent that targets human lung tissue. PURPOSE OF THE STUDY: The purpose of this investigation is to characterize the expression of sulfiredoxin-1 (SRXN1) and peroxiredoxin (PRDXs) genes and oxidative stress (OS) status in human lung after exposure to SM. MATERIALS AND METHODS: Lung biopsy specimens bronchoalveolar lavage (BAL) fluids were provided from SM-exposed patients (n = 6) and controls (n = 5). Changes in gene expression were measured using RT(2) Profiler PCR Array. OS was considered by measuring BAL fluid levels of malondialdehyde (MDA) and protein carbonyls (PC). RESULTS: Mean of MDA and PC values in BAL fluid of patients (0.6467 +/- 0.05922 nmol/l and 1.391 +/- 0.421 nmol/mg, respectively) was higher than in controls (0.486 +/- 0.04615 nmol/l and 0.949 +/- 0.149 nmol/mg, respectively). Expression of all examined genes was in the order PRDX1> PRDX3> PRDX6> SRXN1> PRDX2> PRDX4> PRDX5. Among the most upregulated genes was the PRDX1, which was overexpressed by 10.1029-fold (p = 0.000634). SM-exposed individuals demonstrated expression of PRDX3 4.6231 (p = 0.000134), PRDX6 3.4964 (p = 0.001102), SRXN1 3.3719 (p < 0.0001) and PRDX2 2.7725-folds (p = 0.000383) higher than those of controls that reveal. CONCLUSIONS: Upregulation of PRDXs and SRXN1 genes may be because of reactive oxygen species (ROS) production and OS in lung tissue of patients after SM exposure. Expression of SRXN1 and PRDXNs genes, especially I, II, III, and VI is increased in SM-injured lungs, suggesting the induction of cellular responses to increased production of ROS and OS in lung of the patients. Therefore, sulfiredoxin and peroxiredoxins can be targeted as biomarkers of OS in these patients. PMID- 27266576 TI - The Effect of Education on Upper Extremity Function in Patients with Lymphedema after Breast Cancer Treatments. AB - BACKGROUND: The aim of this study was to evaluate the effects of education on the upper extremity functions of patients with lymphedema (LE) after breast cancer treatments. METHODS: Thirty-eight patients with LE after breast cancer treatments participated in the study. The patients were separated into two groups. Group 1 (n = 19) was educated about the causes and symptoms of LE and the methods for minimizing complications from LE, such as skin care, changes that must be made in daily life activities, exercises, and protective clothing. Group 2 (n = 19) was treated through standard means (surgical, chemotherapy, radiotherapy). A universal goniometer was used to assess the range of motion of the upper extremity of the patients. The Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) and the Shoulder Pain and Disability Index (SPADI) were used to assess shoulder function. The measures were carried out once by the same physiotherapist. The chi-square and Mann-Whitney U tests were used to analyze the data. RESULTS: Group 1, educated about LE, performed better than the other group in shoulder flexion range. When shoulder abduction, internal-external rotation, and elbow flexion motions were compared by using the DASH and SPADI, no significant difference was observed between the groups (p > 0.05). However, when shoulder function was compared, Group 1 was better. There was no significant difference between the groups when the severity of LE was compared. CONCLUSION: This study underscores the need to develop and implement strategies for LE prevention and education for all breast cancer patients. PMID- 27266578 TI - Developmental timing of suicide attempts and cardiovascular risk during young adulthood. AB - OBJECTIVE: Self-control/self-regulation has received increased attention in health research. Suicide attempts index severe dysregulation in emotional, behavioral, and/or physiological domains. The current study tested whether own and/or others' suicide attempts during the early life course predicted cardiovascular risk by young adulthood and whether developmental timing of suicide attempts, sex of the person, and source of suicide attempts exposure modified these associations. METHOD: Data came from the National Longitudinal Study of Adolescent to Adult Health (Add Health). At each assessment during Waves I-IV (covering approximately ages 12-32 years), participants reported whether they and/or a friend/family member had attempted suicide. At Wave IV, trained interviewers assessed participants' obesity and hypertension and collected bloodspots from which high-sensitivity C-reactive protein (hs-CRP) was assayed. Sample sizes in the present analyses ranged from n = 7,884 to n = 8,474. RESULTS: Exposure to own and others' suicide attempts during adolescence was relatively common. In males, suicide attempts during adolescence (~age 15 years) were associated with hypertension and elevated inflammation more than 1 decade later. Associations among suicide attempts by others and cardiovascular risk also emerged. CONCLUSIONS: Exposure to one's own or others' severe dysregulation in the form of suicide attempts during the early life course signals risk for cardiovascular health problems by the late twenties. Adolescent males who attempted suicide and individuals exposed to suicide attempts in their social network may benefit from a dual focus on mental and physical health in care. (PsycINFO Database Record PMID- 27266579 TI - High Spin Polarization at Ferromagnetic Metal-Organic Interfaces: A Generic Property. AB - A high spin polarization of states around the Fermi level, EF, at room temperature has been measured in the past at the interface between a few molecular candidates and the ferromagnetic metal Co. Is this promising property for spintronics limited to these candidates? Previous reports suggested that certain conditions, such as strong ferromagnetism, i.e., a fully occupied spin-up d band of the ferromagnet, or the presence of pi bonds on the molecule, i.e., molecular conjugation, needed to be met. What rules govern the presence of this property? We have performed spin-resolved photoemission spectroscopy measurements on a variety of such interfaces. We find that this property is robust against changes to the molecule and ferromagnetic metal's electronic properties, including the aforementioned conditions. This affirms the generality of highly spin-polarized states at the interface between a ferromagnetic metal and a molecule and augurs bright prospects toward integrating these interfaces within organic spintronic devices. PMID- 27266580 TI - Codelivery of a miR-124 Mimic and Obatoclax by Cholesterol-Penetratin Micelles Simultaneously Induces Apoptosis and Inhibits Autophagic Flux in Breast Cancer in Vitro and in Vivo. AB - Penetratin is a classical cell-penetrating peptide with the potential to assist in the transmembrane delivery of proteins or drugs. However, the synthesis and application of cholesterol-penetratin (Chol-P) conjugates as nonviral delivery systems for microRNAs or drugs have not previously been reported. In this study, the amphiphilic Chol-P was shown to self-assemble into micelles and efficiently deliver miR-124 and obatoclax. The codelivered miR-124-M-Oba had a homogeneous particle size and a positive zeta potential. Treatment with miR-124 mincreased cytotoxicity, and cell proliferation, was promoted by miR-124 inhibitor-loaded micelles in MCF-7 human breast cancer cells. Moreover, the inhibitory effects on cell proliferation, colony formation, and cell migration were increased in the miR-124-M-Oba group compared to the miR-124-M group. miR-124-M-Oba induced higher levels of mitochondrial apoptosis via Bax and caspase-9 activation. In addition, we found that the cationic Chol-P and miR-124-M could potently induce autophagy, and miR-124 was degraded in the corresponding autophagolysosomes. The obatoclax encapsulated in miR-124-M-Oba could inhibit the degradation of miR-124 and p62 in autophagolysosomes, which consequently maintained the concentration of miR-124 in breast cancer cells. Furthermore, miR-124-M-Oba potently inhibited tumor growth in subcutaneous xenograft breast cancer models. In summary, the miR-124-M-Oba prepared in this work showed improved apoptosis induction and autophagic flux inhibitory effects in MCF-7 cells, and miR-124-M-Oba may have potential applications in breast cancer therapy. PMID- 27266582 TI - Potential of risk-based population guidelines to reduce cardiovascular risk in a large integrated health system. AB - OBJECTIVES: We evaluated an alternative way to implement guidelines using an automated risk calculator and risk-based decision tool to calculate patients' risk of cardiovascular disease (CVD) and recommend therapies. We compared such an approach with traditional guidelines. STUDY DESIGN: A retrospective cohort study of 1,506,109 Kaiser Permanente Southern California members 35 years or older. METHODS: We estimated 3-year risks of fatal and nonfatal myocardial infarction and stroke using an independently developed risk calculator, then graphically compared risks with observed outcomes. We used the area under the receiver operating characteristics curve to assess discrimination, and the Hosmer-Lemeshow statistic to test fit. We compared the characteristics and outcomes of populations identified for medication therapy by the risk-based decision tool and traditional guidelines using bivariate statistics. RESULTS: A risk score was obtained in 72% (1,082,158) of members. The risk calculator was fairly good in discrimination: the area under the curve was 0.774 (95% CI, 0.770-0.779) for myocardial infarction and 0.805 (95% CI, 0.801-0.808) for stroke. Predictiveness and fit was good based on graphical analysis and Hosmer-Lemeshow P < .0001. The risk-based decision tool identified high-risk patients for treatment who were not identified by traditional guidelines (3.80% of all those identified for statins, 3.04% for antihypertensives), as well as low-risk patients who were identified by guidelines (3.80% for statins, 2.51% for antihypertensives). CONCLUSIONS: The risk calculator provided risk estimates in most patients and demonstrated fairly good discrimination and predictiveness. The risk-based decision tool identified high-risk patients for treatment not identified by traditional guidelines, as well as low-risk patients for whom treatment may be unnecessary. PMID- 27266581 TI - Breast cancer multigene testing trends and impact on chemotherapy use. AB - OBJECTIVES: A 21-gene test that predicts recurrence risk among women with hormone receptor positive (HR+), localized breast cancer was nationally recommended in 2007, but we know little about its subsequent impact. We evaluated: a) patient characteristics associated with test use, b) correlations between Recurrence Score (RS) and chemotherapy, and c) whether test introduction was associated with a reduction in chemotherapy use. STUDY DESIGN: Retrospective cohort study. METHODS: The Kaiser Permanente Northern California tumor registry and electronic health records from 2005 to 2012 were used to identify HR+, human epidermal growth factor receptor 2 negative, node-negative cancers. Analyses used logistic regression with propensity score matching and 2-level logistic regression. RESULTS: Of the 7004 patients who met guidelines for testing, 22% were tested and 26% had chemotherapy. Test use was more likely in younger women (for ages 40-49 years vs 50-64 years: odds ratio [OR], 1.22; 95% CI, 1.04-1.44), in women with tumors sized 1.0 to 2.0 cm versus > 2 cm (OR, 1.20; 95% CI, 1.03-1.40), and in women from higher-income neighborhoods (for each $10,000 increase in area median income: OR, 1.05; 95% CI, 1.03-1.07). Among patients with low RS, 8% had chemotherapy versus 72% among patients with high RS (P < .01). In propensity score-matched analyses, testing was associated with an absolute reduction of 6.2% in the proportion of women receiving chemotherapy (95% CI, 2.9%-9.5%); the 2 level model showed a similar but nonsignificant (P = .14) association. CONCLUSIONS: The 21-gene test is used in a minority of eligible patients in this integrated plan. Its use appears to be associated with a modest decrease in overall chemotherapy use. PMID- 27266583 TI - Enhanced primary care and impact on quality of care in Massachusetts. AB - OBJECTIVES: Using Behavioral Risk Factor Surveillance System (BRFSS) telephone survey data, we evaluated whether individuals who reported access to enhanced primary care features experienced improved quality of care. STUDY DESIGN: Cross sectional population-level survey. METHODS: We assessed a sample of 16,731 Massachusetts residents contacted by telephone using random-digit dialing, to complete the BRFSS in 2008. A randomized subset of 5693 respondents received an additional 5-question enhanced primary care assessment module. We defined an "enhanced" primary care group as those who reported having a regular, personal provider and responded that their provider "always" or "almost always" 1) had knowledge of their medical history, 2) gave them an appointment right away when necessary, 3) was up-to-date in their knowledge of the patient's specialist care, and 4) asked them about all of their medications. Multivariable logistic regression was used to compare the "enhanced" versus "usual care" groups and assess several quality process measures. RESULTS: Nearly one-third of participants endorsed having indicators of enhanced care, and this group reported significantly higher rates of diabetes process measures (56% vs 38%), cholesterol screening (89% vs 81%), influenza vaccination (57% vs 49%), pneumonia vaccination (51% vs 43%), and lower cost and/or access barriers to care (22% vs 33%). CONCLUSIONS: Enhanced primary care was associated with improved self-reported quality outcomes in a statewide telephone survey. A brief, 5-question module provided a novel population measure of access to enhanced primary care. This is a scalable option for other states hoping to characterize their own primary care improvement efforts through the patient-centered medical home model. PMID- 27266584 TI - Referring wisely: orthopedic referral guidelines at an academic institution. AB - OBJECTIVES: To develop local orthopedic guidelines for use in referral decision support and electronic consultation programs at University of California, San Francisco Health. STUDY DESIGN: Modified Delphi method. METHODS: We performed a 2 phase modified Delphi study to identify consensus between primary care and orthopedic clinicians for common musculoskeletal problems. RESULTS: Clinicians agreed that confirming patient interest in an orthopedic procedure should be completed prior to referral in 81% of clinical scenarios, as well as conservative management in 80%, physical therapy in 60%, and x-ray prior to referral in 42% of scenarios. Clinicians agreed an MRI should not be performed prior to referral in most (58%) clinical scenarios. CONCLUSIONS: In the absence of national guidelines, a process for local guideline generation is needed in order to provide nuanced and detailed decision support at the point of referral. The Delphi method proved an effective process to achieve this end. PMID- 27266585 TI - A cost-effectiveness analysis of over-the-counter statins. AB - OBJECTIVES: To estimate the costs and benefits of over-the-counter (OTC) statins under the 2013 American College of Cardiology/American Heart Association guidelines. STUDY DESIGN: A 10-year cost-effectiveness model using a health system perspective was developed to analyze the impact of making an OTC statin drug available. METHODS: We calibrated the model by using nationally representative survey data on statin use and cardiovascular risk, data from clinical studies on the safety and efficacy of statins, and data from a study on consumer decisions to use an OTC statin. RESULTS: We estimated that OTC statins would result in 252,359 fewer major coronary events, 41,133 fewer strokes, and 135,299 fewer coronary revascularization procedures over 10 years, as well as reduce coronary heart disease- and stroke-related deaths by 68,534 over the same time frame. These averted events would save more than $10.8 billion in healthcare costs while the costs of drug therapy would increase by $28.3 billion. Increased statin utilization is estimated to cause 3864 more cases of rhabdomyolysis-a very rare but severe side effect of statins. The estimated incremental cost effectiveness ratio (ICER) of OTC statins was $5667 per quality-adjusted life year, and the 95% CI of the ICER was $1384 to $12,701. CONCLUSIONS: With proper labeling and consumer education, it is highly likely that OTC statins would be cost-effective, as they significantly improve population health without large increases in healthcare costs. PMID- 27266586 TI - Evaluations of Corneas in Eyes with Isolated Iris Coloboma. AB - PURPOSE: We aimed to evaluate the differences in the corneas of eyes with isolated iris coloboma. METHODS: This study was designed as a prospective study. Among patients who applied to our hospital within the last 3-year period, those with isolated iris coloboma in one eye and a completely normal contralateral eye were included in the study. In addition to a complete ophthalmologic examination, all patients were scanned by Pentacam Scheimpflug camera in the dark, and a corneal endothelium cell count was taken using a Topcon Specular Microscope. Data entered using SPSS software were then evaluated by paired t-test; p < 0.05 value was considered statistically significant. RESULTS: Nine patients, seven men and two women, with a mean age of 35.77 +/- 22.50 (range 8-60) years, were included in the study. In comparison to normal eyes, the colobomatous eyes were statistically found to have lower keratometry values in diopters (43.82 +/- 2.17, 44.46 +/- 1.86; p = 0.040), a greater negative asphericity (Q value) (-0.38 +/- 0.07, -0.22 +/- 0.20; p = 0.042), increased corneal thickness (569.78 +/- 25.42, 537.33 +/- 27.36; p < 0.001), decreased anterior chamber depth (2.50 +/- 0.32, 2.81 +/- 0.50; p = 0.005), a shallower angle (30.51 +/- 10.68, 35.29 +/- 9.99; p = 0.057), higher best-fit sphere (BFS) values of the anterior and posterior corneal surfaces (7.88 +/- 0.39, 7.67 +/- 0.37; p = 0.001; 6.40 +/- 0.26, 6.23 +/ 0.19; p = 0.006), larger pupil diameter (3.48 +/- 0.49, 2.80 +/- 0.34; p = 0.001), smaller horizontal corneal diameter (HCD) (11.06 +/- 0.42; 11.26 +/- 0.45; p = 0.009), and higher value of endothelial cell density (ECD) (3161 +/- 431; 2923 +/- 590; p = 0.031). CONCLUSION: We have determined that a number of factors such as keratometry values, particularly of the corneal endothelium, are different from those of normal eyes. These differences should be taken into account in the follow-up and treatment of eyes with iris coloboma. PMID- 27266587 TI - Campylobacter geochelonis sp. nov. isolated from the western Hermann's tortoise (Testudo hermanni hermanni). AB - During a screening study to determine the presence of species of the genus Campylobacter in reptiles, three putative strains (RC7, RC11 and RC20T) were isolated from different individuals of the western Hermann's tortoise (Testudo hermanni hermanni). Initially, these isolates were characterized as representing Campylobacterfetus subsp. fetus by multiplex PCR and partial 16S rRNA gene sequence analysis. Further whole- genome characterization revealed considerable differences compared to other Campylobacter species. A polyphasic study was then undertaken to determine the exact taxonomic position of the isolates. The three strains were characterized by conventional phenotypic tests and whole genome sequencing. We generated robust phylogenies that showed a distinct clade containing only these strains using the 16S rRNA and atpA genes and a set of 40 universal proteins. Our phylogenetic analysis demonstrates their designation as representing a novel species and this was further confirmed using whole- genome average nucleotide identity within the genus Campylobacter (~80 %). Compared to most Campylobacter species, these strains hydrolysed hippurate, and grew well at 25 degrees C but not at 42 degrees C. Phenotypic and genetic analyses demonstrate that the three Campylobacter strains isolated from the western Hermann's tortoise represent a novel species within the genus Campylobacter, for which the name Campylobactergeochelonis sp. nov. is proposed, with RC20T (=DSM 102159T=LMG 29375T) as the type strain. PMID- 27266589 TI - JC virus/human immunodeficiency virus 1 co-infection in the Brazilian Amazonian region. AB - JC virus (JCV) is a member of the Polyomaviridae family and is associated to a severe disease known as progressive multifocal leukoencephalopathy, PML, which is gradually increasing in incidence as an opportunistic infection among AIDS patients. The present study aimed to investigate the occurrence of JCV among HIV 1 carriers including their types and molecular subtypes and the possible association with disease. Urine samples from 66 HIV-1 infected subjects were investigated for the presence of the virus by amplifying VP1 (215bp) and IG (610bp) regions using the polymerase chain reaction. JCV was detected in 32% of the samples. The results confirmed the occurrence of type B (subtype Af2); in addition, another polyomavirus, BKV, was also detected in 1.5% of samples of the HIV-1 infected subjects. Apparently, there was no significant difference between mono- (HIV-1 only) and co-infected (HIV-1/JCV) subjects regarding their TCD4(+)/TCD8(+) lymphocyte counts or HIV-1 plasma viral load. Self admitted seizures, hearing and visual loses were not significantly different between the two groups. PMID- 27266590 TI - Malaria diagnosis: still a challenge in non-endemic countries. PMID- 27266588 TI - The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation. AB - PURPOSE: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). CONCLUSIONS: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2-30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP ( 2007 ) and BEIR VII (NRC/NAS 2006 ). PMID- 27266591 TI - Disseminated Bacille Calmette-Guerin disease in immunocompetent adult patients. PMID- 27266592 TI - Association of genetic polymorphisms of CISH with the risk of pulmonary tuberculosis in Zahedan, Southeast Iran. AB - BACKGROUND: In the current study we aimed to find out the impact of cytokine inducible Src homology 2 domain protein (CISH) gene polymorphisms on the risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. MATERIALS AND METHODS: Polymorphisms of CISH rs2239751, rs414171, and rs6768300 were determined in 200 PTB patients and 200 healthy subjects using T-ARMS-PCR or PCR-RFLP method. RESULTS: The results showed that rs414171 A>T genotypes significantly decreased the risk of PTB (OR=0.16, 95% CI=0.10-0.27, p<0.0001, AT vs AA; OR=0.31, 95% CI=0.14-0.68, p<0.0001, TT vs AA; OR=0.19, 95% CI=0.12-0.29, p<0.0001, AT+TT vs AA; OR=0.29, 95%CI=0.20-0.42, p<0.0001, T vs A). For rs6768300, the findings indicated that this variant decreased the risk of PTB (OR=0.52, 95% CI=0.33-0.82, p=0.005, CG vs GG; OR=0.57, 95% CI=0.38-0.87, p=0.012, C vs G). No significant association was observed between CISH rs2239751 polymorphism and risk/protection of PTB. CONCLUSION: Our findings indicated that CISH rs414171 and rs6768300 variants might be associated with protection from PTB. PMID- 27266593 TI - Corrigendum to "Antibodies to dendritic neuronal surface antigens in opsoclonus myoclonus ataxia syndrome" [J. Neuroimmunol. 286 (2015) 86-92]. PMID- 27266595 TI - Discussion. PMID- 27266594 TI - The use of machine learning for the identification of peripheral artery disease and future mortality risk. AB - OBJECTIVE: A key aspect of the precision medicine effort is the development of informatics tools that can analyze and interpret "big data" sets in an automated and adaptive fashion while providing accurate and actionable clinical information. The aims of this study were to develop machine learning algorithms for the identification of disease and the prognostication of mortality risk and to determine whether such models perform better than classical statistical analyses. METHODS: Focusing on peripheral artery disease (PAD), patient data were derived from a prospective, observational study of 1755 patients who presented for elective coronary angiography. We employed multiple supervised machine learning algorithms and used diverse clinical, demographic, imaging, and genomic information in a hypothesis-free manner to build models that could identify patients with PAD and predict future mortality. Comparison was made to standard stepwise linear regression models. RESULTS: Our machine-learned models outperformed stepwise logistic regression models both for the identification of patients with PAD (area under the curve, 0.87 vs 0.76, respectively; P = .03) and for the prediction of future mortality (area under the curve, 0.76 vs 0.65, respectively; P = .10). Both machine-learned models were markedly better calibrated than the stepwise logistic regression models, thus providing more accurate disease and mortality risk estimates. CONCLUSIONS: Machine learning approaches can produce more accurate disease classification and prediction models. These tools may prove clinically useful for the automated identification of patients with highly morbid diseases for which aggressive risk factor management can improve outcomes. PMID- 27266596 TI - Cranial nerve injury is associated with dual antiplatelet therapy use and cervical hematoma after carotid endarterectomy. AB - OBJECTIVE: To determine predictors of cranial nerve injury (CNI) after carotid endarterectomy (CEA). METHODS: Consecutive CEAs performed over a 5-year period were enrolled in this study. Outcomes analyzed included 30-day major adverse event rate (composite of stroke, death, and myocardial infarction), death, stroke, disabling stroke, myocardial infarction, cervical hematoma and CNI rate, reoperation, and hospital readmission at 30 days. RESULTS: There were 1258 CEAs were included in the study, 1168 (93%) were performed using an eversion technique. Patients with symptoms comprised 27% of the cohort (n = 340). At 30 days, there were no deaths, 23 major adverse events (1.8%), 11 strokes (0.9%: nine minor, two major), 12 myocardial infarctions (0.9%), 41 cervical hematomas (3.3%), 9 reoperations (0.7%) and 10 hospital readmissions (0.8%). Median duration of stay was 1 day (interquartile range, 1-2 days). CNI rate at discharge was 2.3% (n = 29). Two patients (9%) had more than one cranial nerve affected. The marginal mandibular branch of the facial nerve was most frequently involved (n = 16; 52%), followed by the hypoglossal (n = 9; 29%), the vagus (n = 4; 13%), and the spinal accessory nerve (n = 2; 6%). Horner's syndrome, consistent with an injury to the cervical sympathetic chain, occurred in 13 patients (1%) who had a true cranial nerve affected as well. The vast majority (94%) of these CNIs and all Horner's syndrome neurapraxias were transient; only the two accessory lesions persisted at their follow-up visit (median, 32 months; range, 8-72 months). Significant predictors for CNI included diabetes (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.0-6.2; P = .048), cervical hematoma (OR, 41.7; 95% CI, 13.8-125.4; P < .001), and dual antiplatelet therapy (OR, 4.4; 95% CI, 1.7 11.4; P = .002). CONCLUSIONS: CNI is predominantly a transient complication, but is associated significantly with dual antiplatelet therapy use and the occurrence of a postoperative cervical hematoma. Scrupulous attention to hemostasis might reduce the incidence of CNI. PMID- 27266597 TI - Use of hyperspectral imaging to assess endothelial dysfunction in peripheral arterial disease. AB - BACKGROUND: Hyperspectral imaging (HSI) is a technology that with limited training can noninvasively measure oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin concentrations in the skin to create an oxygenation map. This pilot study determined whether HSI could be used to demonstrate vascular dysfunction in the upper extremity of patients with peripheral artery disease (PAD) and coronary artery disease (CAD). METHODS: This prospective study included 93 consecutive, consented patients presenting to the vascular clinic, with and without diagnosed arterial disease, and healthy volunteers. Patients underwent HSI at the upper arm, forearm, and palm before and after cuff occlusion (50 mm Hg above systolic) for 5 minutes. Medical records of enrolled patients were reviewed for demographic data, medications, surgical history, and other pertinent information. RESULTS: Significant changes occurred with oxyHb, with minimal to no effects on deoxygenated hemoglobin. The highest values of oxyHb were detected in the upper arm, followed by the forearm and hand. The absolute and percentage change in oxyHb measured in the upper arm and forearm was significantly reduced in controls aged >40 years compared with controls aged <40 years. Significant differences were noted in the upper arm oxyHb absolute change in response to cuff occlusion comparing PAD or CAD (n = 47) vs the older control cohort (P = .028). When the 23 patients with PAD only were separated out, the upper arm oxyHb response to cuff occlusion is even more significantly impaired (P < .01) compared with controls. CONCLUSIONS: Our study suggests the ability of HSI to assess the presence of PAD or CAD based on systemic vascular dysfunction at sites remote from the clinically diseased vascular bed. This could enable early screening and tracking of arterial disease patients before the development of clinically advanced disease. PMID- 27266598 TI - Unique Abnormalities in Right Ventricular Longitudinal Strain in Systemic Sclerosis Patients. AB - BACKGROUND: Cardiac involvement in systemic sclerosis (scleroderma [SSc]) adversely affects long-term prognosis, often remaining undetectable despite close clinical examination and 2-dimensional echocardiographic monitoring. Speckle derived strain of the right ventricle (RV) was utilized to detect occult abnormalities in regional and global contractility in SSc patients. METHODS AND RESULTS: A total of 138 SSc patients with technically adequate echocardiograms was studied and compared with 40 age- and sex-matched healthy non-SSc controls. Standard assessment of RV chamber function included tricuspid annular plane systolic excursion and fractional area change. RV longitudinal systolic speckle derived strain was assessed in the basal, mid, and apical free wall. Tricuspid annular plane systolic excursion was not different between groups (P=0.307). Although fractional area change was lower in SSc patients than in controls (mean, 48.9 versus 55; P=0.002), the mean fractional area change was still within the normal range (>35). In contrast, RV longitudinal systolic speckle-derived strain measures were significantly different between groups, both globally (-20.4% versus -17.7%; P=0.005) and regionally: they were decreased in the apex (-8.5% versus -17.1%; P<0.0001) and mid segments (-12.4% versus -20.9%; P<0.0001), and increased in the base (-32.2% versus -23.3%; P=0.0001) for the SSc group. The regional difference in the base compared with the apex was significantly greater for SSc than for controls (P<0.0001 for interaction). The differences observed in regional strain between SSc and control were unchanged after adjusting for RV systolic pressure. CONCLUSIONS: Speckle-derived strain reveals a heterogenous pattern of regional heart strain in SSc that is not detected by conventional measures of function, suggestive of occult RV myocardial disease. PMID- 27266600 TI - Subclinical Right Ventricular Dysfunction by Strain Analysis: Refining the Targets of Echocardiographic Imaging in Systemic Sclerosis. PMID- 27266599 TI - Cognitive Machine-Learning Algorithm for Cardiac Imaging: A Pilot Study for Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy. AB - BACKGROUND: Associating a patient's profile with the memories of prototypical patients built through previous repeat clinical experience is a key process in clinical judgment. We hypothesized that a similar process using a cognitive computing tool would be well suited for learning and recalling multidimensional attributes of speckle tracking echocardiography data sets derived from patients with known constrictive pericarditis and restrictive cardiomyopathy. METHODS AND RESULTS: Clinical and echocardiographic data of 50 patients with constrictive pericarditis and 44 with restrictive cardiomyopathy were used for developing an associative memory classifier-based machine-learning algorithm. The speckle tracking echocardiography data were normalized in reference to 47 controls with no structural heart disease, and the diagnostic area under the receiver operating characteristic curve of the associative memory classifier was evaluated for differentiating constrictive pericarditis from restrictive cardiomyopathy. Using only speckle tracking echocardiography variables, associative memory classifier achieved a diagnostic area under the curve of 89.2%, which improved to 96.2% with addition of 4 echocardiographic variables. In comparison, the area under the curve of early diastolic mitral annular velocity and left ventricular longitudinal strain were 82.1% and 63.7%, respectively. Furthermore, the associative memory classifier demonstrated greater accuracy and shorter learning curves than other machine-learning approaches, with accuracy asymptotically approaching 90% after a training fraction of 0.3 and remaining flat at higher training fractions. CONCLUSIONS: This study demonstrates feasibility of a cognitive machine-learning approach for learning and recalling patterns observed during echocardiographic evaluations. Incorporation of machine-learning algorithms in cardiac imaging may aid standardized assessments and support the quality of interpretations, particularly for novice readers with limited experience. PMID- 27266601 TI - Unleashing the Potential of Machine-Based Learning for the Diagnosis of Cardiac Diseases. PMID- 27266617 TI - Lipocalin-2 mediates non-alcoholic steatohepatitis by promoting neutrophil macrophage crosstalk via the induction of CXCR2. AB - BACKGROUND & AIMS: Inflammatory cell infiltration in the liver is a hallmark of non-alcoholic steatohepatitis (NASH). However, the pathological events which trigger the infiltration of inflammatory cells to mediate NASH pathogenesis remains poorly understood. This study aims to investigate the role of neutrophil derived lipocalin 2 (LCN2) in mediating the transition from simple steatosis to NASH. METHODS: Animal models of NASH were induced by high fat high cholesterol (HFHC) diet and methionine- and choline-deficient (MCD) diet in LCN2 knockout mice and wild-type controls. RESULTS: Circulating levels of LCN2 and its hepatic expression were markedly increased in both murine models and human subjects with NASH, and these changes were associated with increased infiltration of neutrophils. In diet-induced NASH models, hepatic injury, necroinflammation and infiltration of neutrophils and macrophages were substantially attenuated by genetic depletion of LCN2. In contrast, chronic infusion of recombinant LCN2 exacerbated diet-induced liver injury, inflammation and macrophage accumulation in a neutrophil-dependent manner. Primary mouse neutrophils lacking LCN2 exhibited a defective migration capacity, which can be reversed by replenishment with recombinant LCN2. Mechanistically, LCN2 induced the expression of the chemokine (C-X-C motif) receptor 2 (CXCR2), thereby leading to activation of ERK1/2 and production of proinflammatory chemokines. LCN2-induced inflammation, infiltration of macrophages and liver injury was abrogated in CXCR2-deficient mice. CONCLUSIONS: These findings demonstrated that LCN2 acts as a central mediator to facilitate the crosstalk between neutrophils and hepatic macrophages via induction of the chemokine receptor CXCR2, thereby exacerbating steatohepatitis. LAY SUMMARY: Lipocalin-2 levels in blood and the liver were markedly increased in both mouse models and human subjects with NASH, and these changes were associated with increased infiltration of neutrophils in the liver. In diet-induced NASH models, hepatic injury, necroinflammation and infiltration of neutrophils and macrophages were substantially attenuated by genetic depletion of lipocalin-2, but was augmented by chronic infusion of recombinant lipocalin-2. Lipocalin-2 induced the expression of the chemokine receptor CXCR2, thereby leading to activation of the mitogen-activated protein (MAP) kinase ERK1/2 and production of proinflammatory chemokines. Lipocalin-2-induced inflammation, infiltration of macrophages and liver injury was abrogated in CXCR2-deficient mice. PMID- 27266618 TI - Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. AB - BACKGROUND & AIMS: The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey. METHODS: We analyzed data for 6474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2093 patients who underwent LR and 4381 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 1058 patients (66.1% of the LR group). RESULTS: In the Child Pugh A patients, the median survival time (MST) in the LR group was 1.77years longer than that in the non-LR group (2.87years vs. 1.10years; p<0.001) and 0.88years longer than that in the non-LR group (2.45years vs. 1.57years; p<0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of age, etiology of HCC, tumor marker elevation, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative 90-day mortality rate was 3.7% (68 patients). CONCLUSIONS: As long as the PVTT is limited to the first-order branch, LR is associated with a longer survival outcome than non-surgical treatment. LAY SUMMARY: The presence of portal vein tumor thrombosis in patients with hepatocellular carcinoma is regarded as indicating an advanced stage, and liver resection is not recommended. We performed a multicenter, nationwide study to assess the survival benefit of liver resection in hepatocellular carcinoma patients with portal vein tumor thrombosis using propensity score-based matching. As long as the portal vein tumor thrombosis is limited to the first-order branch, liver resection is associated with a longer survival outcome than non-surgical treatment. PMID- 27266619 TI - Congenital dislocation of the knee at birth - Part I: Clinical signs and classification. AB - INTRODUCTION: Congenital dislocation of the knee (CDK) is rare, and clinical semiology at birth is not always suitably analyzed. Existing classifications fail to guide treatment. The aim of the present study was to develop a CDK classification for the neonatal period. HYPOTHESIS: A classification based on neonatal severity of clinical signs is easy to implement on simple criteria. MATERIAL AND METHODS: Fifty-one CDKs (40 patients) seen neonatally were included. Three types could be distinguished in terms of reduction and stability: type I, easily reducible CDK, with reduction snap when the femoral condyles pass in flexion, remaining stable in flexion; type II, "recalcitrant" dislocation, reducible by posteroanterior "piston" but unstable, with iterative dislocation once posteroanterior pressure on the condyles is relaxed; and type III, irreducible. The number of anterior skin grooves, global range of motion, flexion deficit and reduction stability were noted for each type. RESULTS: Mean age at first consultation was 5.6 days (range: 0-30). CDK was type I, II and III in respectively 28, 16 and 7 cases. Number of skin grooves, flexion and baseline range of motion were greater in type I than types II and III. CONCLUSION: The present neonatal clinical classification is original, logical and simple. It may be useful for prognosis and guiding treatment. LEVEL OF EVIDENCE: IV, single center retrospective series. PMID- 27266620 TI - Patients with Low National Institutes of Health Stroke Scale Scores Have Longer Door-to-Needle Times: Analysis of a Telestroke Network. AB - BACKGROUND: The benefits of intravenous tissue-type plasminogen activator (IV tPA) in acute ischemic stroke (AIS) are time dependent. Because emergency rooms quickly initiate a stroke alert with more severe symptoms, we hypothesized that patients with lower National Institutes of Health Stroke Scale (NIHSS) scores, indicating a less severe stroke, would have longer door-to-needle (DTN) times compared to patients with higher NIHSS scores. METHODS: Data obtained from the 19 hospital Providence Stroke Registry were used to identify AIS patients who received IV-tPA within 4.5 hours of last-known-well. NIHSS scores were obtained prior to tPA administration at the time of emergency department presentation and categorized as low-NIHSS (score = 0-5) or high-NIHSS (score = 6-42) strokes. Median DTN times were collected for both groups as the primary outcome variable. Linear mixed-effects regression models were used to assess the effect of NIHSS scores on DTN and its 2 components: door-to-CT (DCT) and CT-to-needle (CTN) times. RESULTS: We identified 692 AIS patients who received IV-tPA within 4.5 hours of last-known-well, with 198 patients presenting with low-NIHSS strokes and 494 patients with high-NIHSS strokes. In multivariable analysis, median DTN time was estimated to be 18% higher for low-NIHSS strokes than high-NIHSS strokes after adjusting for covariates (P < .001). Median DCT times were also higher for low-NIHSS (19 minutes) compared to high-NIHSS (11 minutes) strokes after adjusting for covariates (P < .001), whereas CTN times were unchanged (P = .055). CONCLUSION: In AIS patients receiving IV-tPA in a telestroke network, lower NIHSS scores were associated with longer DTN and DCT times. PMID- 27266621 TI - Ischemic Stroke and Six Genetic Variants in CRP, EPHX2, FGA, and NOTCH3 Genes: A Meta-Analysis. AB - BACKGROUND: Ischemic stroke (IS) is a leading cause of death and disability worldwide. As genetic heritability for IS is estimated at about 35%-40%, the identification of genetic variants associated with IS risk is of great importance. The main objective of this study was to carry out a meta-analysis for polymorphisms in CRP, EPHX2, FGA, and NOTCH3 genes and the risk for IS. METHODS: Literature search for 6 candidate polymorphisms and IS was conducted using HuGE Navigator, PubMed, and Google Scholar databases. Meta-Analyst program was used to calculate pooled odds ratios (ORs) with a random effects model. RESULTS: Twenty five published studies for 6 candidate polymorphisms were included: CRP-rs1800947 (5 studies), CRP-rs1205 (3 studies), EPHX2-rs751141 (5 studies), FGA-rs6050 (6 studies), NOTCH3-rs3815188 (3 studies), and NOTCH3-rs1043994 (3 studies), for a total number of 7,825 IS cases and 56,532 control subjects. We did not find significant pooled ORs (P values > .05) for any of the genetic variants evaluated in this work. CONCLUSIONS: Our meta-analysis results did not show significant associations between these 6 polymorphisms in 4 candidate genes and IS, despite the functional role of some of these single nucleotide polymorphisms (e.g., rs6050 in FGA gene). Future studies are needed to identify additional main genetic risk factors for IS in different populations. PMID- 27266622 TI - Impact of Patients' Income on Stroke Prognosis. AB - BACKGROUND: For patients diagnosed with stroke, the association between socioeconomic status and patient outcomes is poorly understood. Our objective was to define the impact of patients' socioeconomic status on their prognosis after stroke in the United States. METHODS: Utilizing the Nationwide Inpatient Sample, we identified discharges involving a diagnosis of stroke from 2008 to 2013. Cohort was dichotomized to low-income patients (L-patients) and not-low-income patients (NL-patients). Z-test statistic was used to test the impact of income on stroke outcome. RESULTS: The reported annual total in-hospital mortality for L patients and NL-patients diagnosed with stroke at U.S. hospitals decreased significantly during the study period (P < .001). The mortality of L-patients decreased significantly from 1759 (4.16%) to 955 (2.54%) during study period. Similarly, NL-patients' mortality decreased significantly from 4818 (4.52%) to 2300 (2.47%) during the same period. The difference between the annual total in hospital mortality for L-patients and NL-patients due to stroke was statistically significant throughout the entire study period (P < .0001). Notably, from 2008 to 2013, the annual total routine discharges, annual total discharges to short-term hospital, annual total discharges to another institution, and annual total discharges to home health care were statistically significantly different between the 2 populations of patients (P < .0001). CONCLUSIONS: Socioeconomic status has an impact on patient outcome after treatment of stroke in hospitals in the United States. Further study is needed to investigate the etiology of these differences between patients' socioeconomic status and their clinical outcomes after stroke. PMID- 27266624 TI - Historical Study (1986-2014): Improvements in Nutritional Status of Dialysis Patients. AB - OBJECTIVE: Malnutrition is common in dialysis patients and is associated with adverse clinical outcomes. Despite an increased focus on improved nutrition in dialysis patients, it is claimed that the prevalence of malnutrition in this group of patients has not changed during the last decades. Direct historical comparisons of the nutritional status of dialysis patients have never been published. To directly compare the nutritional status of past and current dialysis patients, we implemented the methodology of a study from 1986 on a population of dialysis patients in 2014. DESIGN: Historical study comparing results of two cross-sectional studies performed in 1986 and 2014. SETTING: We compared the nutritional status of hemodialysis (HD) and peritoneal dialysis (PD) patients attending the dialysis center at Roskilde Hospital, Denmark, in February to June 2014, with that of HD and PD patients treated at the dialysis center at Fredericia Hospital, Denmark, in April 1986. SUBJECTS: Maintenance PD and HD patients (n = 64 in 2014 and n = 48 in 1986). METHODS: We performed anthropometry (body weight, triceps skinfold, and midarm muscle circumferences [MAMCs]) and determined plasma transferrin. MAIN OUTCOME MEASURE: Relative body weight, triceps skinfold, MAMC, body mass index, and prevalence of protein-caloric malnutrition as defined in the original study from 1986. RESULTS: Average relative body weight, triceps skinfold, MAMC, and body mass index were significantly higher in 2014 compared with 1986. The prevalence of protein caloric malnutrition was significantly lower in 2014 (18%) compared with 1986 (52%). CONCLUSIONS: The nutritional status of maintenance dialysis patients has improved during the last 3 decades. The reason for this improvement could not be identified in the present study, but the most likely contributors are the higher prevalence of obesity in the general population, less predialytic malnutrition, and an improved focus on nutrition in maintenance dialysis patients. PMID- 27266623 TI - Differences in Clinical Characteristics between Patients with Transient Ischemic Attack Whose Symptoms Do and Do Not Persist on Arrival. AB - BACKGROUND: Symptoms of transient ischemic attack (TIA) persist on arrival and subsequently resolve in some patients admitted to hospitals early after onset. Differences in clinical characteristics between patients with acute TIA whose symptoms do and do not persist on arrival remain unclear. METHODS: We retrospectively extracted data of consecutive TIA patients with an onset-to-door time (ODT) of 24 hours or less and without a history of stroke from a multicenter TIA database. Clinical characteristics were compared between patients with and without persisting symptoms on arrival. RESULTS: Two hundred sixty-six patients (158 men, 68.0 +/- 12.9 years) were included. Of the total number of patients, 105 (39.5%) had persisting symptoms with a mean National Institutes of Health Stroke Scale score of 2.4 (median, 1.0). Patients with persisting symptoms were more likely to have sensory disorder, ambulance-transported admission, long duration TIA (>=60 minutes), and shorter ODT than those without. Multivariate analysis showed that sensory disorder (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.35-4.77), ambulance-transported admission (OR 1.80, 95% CI 1.00 3.28), and long-duration TIA (OR 3.96, 95% CI 2.12-7.71) were positively associated and that an ODT of more than 12 hours (OR .18, 95% CI .04-.63) was inversely associated with the presence ofpersisting symptoms. Patients with persisting symptoms were more likely to be examined by a stroke physician at first (69% versus 57%, P = .049) and then hospitalized in a stroke unit (59% versus 43%, P = .010). CONCLUSION: Clinical manifestations and management after admission might differ between patients with acute TIA whose symptoms do and do not persist on arrival. PMID- 27266625 TI - Soil bacteria showing a potential of chlorpyrifos degradation and plant growth enhancement. AB - BACKGROUND: Since 1960s, the organophosphate pesticide chlorpyrifos has been widely used for the purpose of pest control. However, given its persistence and toxicity towards life forms, the elimination of chlorpyrifos from contaminated sites has become an urgent issue. For this process bioremediation is the method of choice. RESULTS: Two bacterial strains, JCp4 and FCp1, exhibiting chlorpyrifos degradation potential were isolated from pesticide contaminated agricultural fields. These isolates were able to degrade 84.4% and 78.6% of the initial concentration of chlorpyrifos (100mgL(-1)) within a period of only 10 days. Based on 16S rRNA sequence analysis, these strains were identified as Achromobacter xylosoxidans (JCp4) and Ochrobactrum sp. (FCp1). These strains exhibited the ability to degrade chlorpyrifos in sterilized as well as non-sterilized soils, and were able to degrade 93-100% of the input concentration (200mgkg(-1)) within 42 days. The rate of degradation in inoculated soils ranged from 4.40 to 4.76mg( 1)kg(-1)d(-1) with rate constants varying between 0.047 and 0.069d(-1). These strains also displayed substantial plant growth promoting traits such as phosphate solubilization, indole acetic acid production and ammonia production both in absence as well as in the presence of chlorpyrifos. However, presence of chlorpyrifos (100 and 200mgL(-1)) was found to have a negative effect on indole acetic acid production and phosphate solubilization with percentage reduction values ranging between 2.65-10.6% and 4.5-17.6%, respectively. Plant growth experiment demonstrated that chlorpyrifos has a negative effect on plant growth and causes a decrease in parameters such as percentage germination, plant height and biomass. Inoculation of soil with chlorpyrifos-degrading strains was found to enhance plant growth significantly in terms of plant length and weight. Moreover, it was noted that these strains degraded chlorpyrifos at an increased rate (5.69mg(-1)kg(-1)d(-1)) in planted soil. CONCLUSION: The results of this study clearly demonstrate that the chlorpyrifos-degrading strains have the potential to develop into promising candidates for raising the productivity of crops in pesticide contaminated soils. PMID- 27266626 TI - Production of mycelial biomass by the Amazonian edible mushroom Pleurotus albidus. AB - Edible mushroom species are considered as an adequate source of food in a healthy diet due to high content of protein, fiber, vitamins, and a variety of minerals. The representatives of Pleurotus genus are characterized by distinct gastronomic, nutritional, and medicinal properties among the edible mushrooms commercialized worldwide. In the present study, the growth of mycelial biomass of Pleurotus albidus cultivated in submerged fermentation was evaluated. Saccharose, fructose, and maltose were the three main carbon sources for mycelial biomass formation with corresponding yields of 7.28gL(-1), 7.07gL(-1), and 6.99gL(-1). Inorganic nitrogen sources did not stimulate growth and the optimal yield was significantly higher with yeast extract (7.98gL(-1)). The factorial design used to evaluate the influence of saccharose and yeast extract concentration, agitation speed, and initial pH indicated that all variables significantly influenced the production of biomass, especially the concentration of saccharose. The greater amount of saccharose resulted in the production of significantly more biomass. The highest mycelial biomass production (9.81gL(-1)) was reached in the medium formulated with 30.0gL(-1) saccharose, 2.5gL(-1) yeast extract, pH 7.0, and a speed of agitation at 180rpm. Furthermore, P. albidus manifested different aspects of morphology and physiology under the growth conditions employed. Media composition affected mycelial biomass production indicating that the diversification of carbon sources promoted its improvement and can be used as food or supplement. PMID- 27266627 TI - Streptomyces lunalinharesii 235 prevents the formation of a sulfate-reducing bacterial biofilm. AB - Streptomyces lunalinharesii strain 235 produces an antimicrobial substance that is active against sulfate reducing bacteria, the major bacterial group responsible for biofilm formation and biocorrosion in petroleum reservoirs. The use of this antimicrobial substance for sulfate reducing bacteria control is therefore a promising alternative to chemical biocides. In this study the antimicrobial substance did not interfere with the biofilm stability, but the sulfate reducing bacteria biofilm formation was six-fold smaller in carbon steel coupons treated with the antimicrobial substance when compared to the untreated control. A reduction in the most probable number counts of planktonic cells of sulfate reducing bacteria was observed after treatments with the sub-minimal inhibitory concentration, minimal inhibitory concentration, and supra-minimal inhibitory concentration of the antimicrobial substance. Additionally, when the treated coupons were analyzed by scanning electron microscopy, the biofilm formation was found to be substantially reduced when the supra-minimal inhibitory concentration of the antimicrobial substance was used. The coupons used for the biofilm formation had a small weight loss after antimicrobial substance treatment, but corrosion damage was not observed by scanning electron microscopy. The absence of the dsrA gene fragment in the scraped cell suspension after treatment with the supra-minimal inhibitory concentration of the antimicrobial substance suggests that Desulfovibrio alaskensis was not able to adhere to the coupons. This is the first report on an antimicrobial substance produced by Streptomyces active against sulfate reducing bacteria biofilm formation. The application of antimicrobial substance as a potential biocide for sulfate reducing bacteria growth control could be of great interest to the petroleum industry. PMID- 27266628 TI - Simultaneous production of amylases and proteases by Bacillus subtilis in brewery wastes. AB - The simultaneous production of amylase (AA) and protease (PA) activity by Bacillus subtilis UO-01 in brewery wastes was studied by combining the response surface methodology with the kinetic study of the process. The optimum conditions (T=36.0 degrees C and pH=6.8) for high biomass production (0.92g/L) were similar to the conditions (T=36.8 degrees C and pH=6.6) for high AA synthesis (9.26EU/mL). However, the maximum PA level (9.77EU/mL) was obtained at pH 7.1 and 37.8 degrees C. Under these conditions, a considerably high reduction (between 69.9 and 77.8%) of the initial chemical oxygen demand of the waste was achieved. In verification experiments under the optimized conditions for production of each enzyme, the AA and PA obtained after 15h of incubation were, respectively, 9.35 and 9.87EU/mL. By using the Luedeking and Piret model, both enzymes were classified as growth-associated metabolites. Protease production delay seemed to be related to the consumption of non-protein and protein nitrogen. These results indicate that the brewery waste could be successfully used for a high scale production of amylases and proteases at a low cost. PMID- 27266629 TI - Diversity of group A rotavirus genes detected in the Triangulo Mineiro region, Minas Gerais, Brazil. AB - Group A rotaviruses are the main causative agent of infantile gastroenteritis. The segmented nature of the viral genome allows reassortment of genome segments, which can generate genetic variants. In this study, we characterized the diversity of the VP7, VP4 (VP8*), VP6, NSP4, and NSP5 genes of the rotaviruses that circulated from 2005 to 2011 in the Triangulo Mineiro (TM) region of Brazil. Samples with genotypes G2 (sublineages IVa-1 and IVa-3), G1 (sublineage I-A), G9 (lineage III), G12 (lineages II and III), G8 (lineage II), G3 (lineage III), P[4] (sublineages IVa and IVb), P[8] (sublineages P[8]-3.6, P[8]-3.3, and P[8]-3.1), I2 (lineage VII), E2 (lineages VI, XII, and X), and H2 (lineage III) were identified. The associations found in the samples were G1, G9, or G12 with P[8] I1-E1-H1; G2 or G8 with P[4]-I2-E2-H2; G12 with I3-E3-H6; and G3 with P[4]-I2-E3 H3 (previously unreported combination). Reassortment events in G2P[4] strains and an apparent pattern of temporal segregation within the lineages were observed. Five TM samples contained genes that exhibited high nucleotide and amino acid identities with strains of animal origin. The present study includes a period of pre- and post-introduction of rotavirus vaccination in all Brazilian territories, thereby serving as a basis for monitoring changes in the genetic constitution of rotaviruses. The results also contribute to the understanding of the diversity and evolution of rotaviruses in a global context. PMID- 27266630 TI - l-(+)-Lactic acid production by Lactobacillus rhamnosus B103 from dairy industry waste. AB - Lactic acid, which can be obtained through fermentation, is an interesting compound because it can be utilized in different fields, such as in the food, pharmaceutical and chemical industries as a bio-based molecule for bio-refinery. In addition, lactic acid has recently gained more interest due to the possibility of manufacturing poly(lactic acid), a green polymer that can replace petroleum derived plastics and be applied in medicine for the regeneration of tissues and in sutures, repairs and implants. One of the great advantages of fermentation is the possibility of using agribusiness wastes to obtain optically pure lactic acid. The conventional batch process of fermentation has some disadvantages such as inhibition by the substrate or the final product. To avoid these problems, this study was focused on improving the production of lactic acid through different feeding strategies using whey, a residue of agribusiness. The downstream process is a significant bottleneck because cost-effective methods of producing high-purity lactic acid are lacking. Thus, the investigation of different methods for the purification of lactic acid was one of the aims of this work. The pH-stat strategy showed the maximum production of lactic acid of 143.7g/L. Following purification of the lactic acid sample, recovery of reducing sugars and protein and color removal were 0.28%, 100% and 100%, respectively. PMID- 27266632 TI - Full genome sequencing of the bluetongue virus-1 isolate MKD20/08/Ind from goat in India. AB - This communication reports full genome sequencing of the bluetongue virus-1 (BTV 1) isolate MKD20/08/Ind from goat in northern India. The total BTV-1 genome size was found to be 19,190bp. A comparison study between the Indian isolate and other global isolates revealed that it belongs to the 'Eastern' BTV topotype. The full genome sequence of BTV-1 will provide vital information on its geographical origin and it will also be proved useful for comparing the Indian isolate with global isolates from other host species. PMID- 27266631 TI - Aminotransferase and glutamate dehydrogenase activities in lactobacilli and streptococci. AB - Aminotransferases and glutamate dehydrogenase are two main types of enzymes involved in the initial steps of amino acid catabolism, which plays a key role in the cheese flavor development. In the present work, glutamate dehydrogenase and aminotransferase activities were screened in twenty one strains of lactic acid bacteria of dairy interest, either cheese-isolated or commercial starters, including fifteen mesophilic lactobacilli, four thermophilic lactobacilli, and two streptococci. The strains of Streptococcus thermophilus showed the highest glutamate dehydrogenase activity, which was significantly elevated compared with the lactobacilli. Aspartate aminotransferase prevailed in most strains tested, while the levels and specificity of other aminotransferases were highly strain- and species-dependent. The knowledge of enzymatic profiles of these starter and cheese-isolated cultures is helpful in proposing appropriate combinations of strains for improved or increased cheese flavor. PMID- 27266633 TI - Staphylococcus xylosus fermentation of pork fatty waste: raw material for biodiesel production. AB - The need for cleaner sources of energy has stirred research into utilising alternate fuel sources with favourable emission and sustainability such as biodiesel. However, there are technical constraints that hinder the widespread use of some of the low cost raw materials such as pork fatty wastes. Currently available technology permits the use of lipolytic microorganisms to sustainably produce energy from fat sources; and several microorganisms and their metabolites are being investigated as potential energy sources. Thus, the aim of this study was to characterise the process of Staphylococcus xylosus mediated fermentation of pork fatty waste. We also wanted to explore the possibility of fermentation effecting a modification in the lipid carbon chain to reduce its melting point and thereby act directly on one of the main technical barriers to obtaining biodiesel from this abundant source of lipids. Pork fatty waste was obtained from slaughterhouses in southern Brazil during evisceration of the carcasses and the kidney casing of slaughtered animals was used as feedstock. Fermentation was performed in BHI broth with different concentrations of fatty waste and for different time periods which enabled evaluation of the effect of fermentation time on the melting point of swine fat. The lowest melting point was observed around 46 degrees C, indicating that these chemical and biological reactions can occur under milder conditions, and that such pre-treatment may further facilitate production of biodiesel from fatty animal waste. PMID- 27266636 TI - [Innate immunity primary immunodeficiencies and infections]. AB - The diagnosis of primary immunodeficiency diseases (PIDs) is important for the early and adaptive care of patients and their families. Among the various known PIDs, a number of them concern the innate immune system, which involve a set of cells and mechanisms involved in the host defense by a nonspecific and fast response. The majority of patients with innate immunity defects have a predisposition to one isolated type of infection (bacterial, viral, or fungal), dependent on the genetic defect involved. This article describes the different PIDs involving innate immunity and the immunological investigations allowing for their diagnosis. PMID- 27266634 TI - Neurofibromin is a novel regulator of Ras-induced reactive oxygen species production in mice and humans. AB - Neurofibromatosis type 1 (NF1) predisposes individuals to early and debilitating cardiovascular disease. Loss of function mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin, leads to accelerated p21(Ras) activity and phosphorylation of multiple downstream kinases, including Erk and Akt. Nf1 heterozygous (Nf1(+/-)) mice develop a robust neointima that mimics human disease. Monocytes/macrophages play a central role in NF1 arterial stenosis as Nf1 mutations in myeloid cells alone are sufficient to reproduce the enhanced neointima observed in Nf1(+/-) mice. Though the molecular mechanisms underlying NF1 arterial stenosis remain elusive, macrophages are important producers of reactive oxygen species (ROS) and Ras activity directly regulates ROS production. Here, we use compound mutant and lineage-restricted mice to demonstrate that Nf1(+/-) macrophages produce excessive ROS, which enhance Nf1(+/-) smooth muscle cell proliferation in vitro and in vivo. Further, use of a specific NADPH oxidase 2 inhibitor to limit ROS production prevents neointima formation in Nf1(+/-) mice. Finally, mononuclear cells from asymptomatic NF1 patients have increased oxidative DNA damage, an indicator of chronic exposure to oxidative stress. These data provide genetic and pharmacologic evidence that excessive exposure to oxidant species underlie NF1 arterial stenosis and provide a platform for designing novels therapies and interventions. PMID- 27266637 TI - [Marble bone disease: The role of SPECT/CT hybrid imaging]. AB - INTRODUCTION: Osteopetrosis is an autosomal metabolic bone disease characterized by a decrease in bone resorption. It can be dominant or recessive. The patient often has increased bone fragility with fractures, which are usually the first sign of disease. Symptoms are variable, ranging from mild hematological disorders to severe neurological complications that can be life threatening. This work reports on the contribution of single-photon emission computed tomography (SPECT)/CT in the diagnosis and management of osteoarticular complications of marble bone disease, based on a clinical case. CASE REPORT: A 2-year-old child, born after a consanguineous marriage, was hospitalized because of mucocutaneous pallor, splenomegaly, failure to thrive, and altered psychomotor development. Radiographic examination showed signs of osteopetrosis. SPECT/CT revealed a double fracture of the right coracoid process and the 10th right rib. DISCUSSION, CONCLUSION: Fractures are a common complication of osteopetrosis. They are spontaneous or associated with minor trauma. SPECT/CT is important in the evaluation of the extension of bone lesions, and it confirms the diagnosis of osteomyelitis or fracture when radiological images are atypical or clinical expression is unusual. PMID- 27266635 TI - Default mode network differences between rigidity- and tremor-predominant Parkinson's disease. AB - BACKGROUND: Parkinson's disease (PD) traditionally is characterized by tremor, rigidity, and bradykinesia, although cognitive impairment also is a common symptom. The clinical presentation of PD is heterogeneous and associated with different risk factors for developing cognitive impairment. PD patients with primary akinetic/rigidity (PDAR) are more likely to develop cognitive deficits compared to those with tremor-predominant symptoms (PDT). Because cognitive impairment in PD appears to be related to changes in the default mode network (DMN), this study tested the hypothesis that DMN integrity is different between PDAR and PDT subtypes. METHOD: Resting state fMRI (rs-fMRI) and whole brain volumetric data were obtained from 17 PDAR, 15 PDT and 24 healthy controls (HCs) using a 3T scanner. PD patients were matched closely to HCs for demographic and cognitive variables, and showed no symptoms of dementia. Voxel-based morphometry (VBM) was used to examine brain gray matter (GM) volume changes between groups. Independent component analysis (ICA) interrogated differences in the DMN among PDAR, PDT, and HC. RESULTS: There was decreased activity in the left inferior parietal cortex (IPC) and the left posterior cingulate cortex (PCC) within the DMN between PDAR and both HC and PDT subjects, even after controlling for multiple comparisons, but not between PDT and HC. GM volume differences between groups were detected at a lower threshold (p < 0.001, uncorrected). Resting state activity in IPC and PCC were correlated with some measures of cognitive performance in PD but not in HC. CONCLUSION: This is the first study to demonstrate DMN differences between cognitively comparable PDAR and PDT subtypes. The DMN differences between PD and HC appear to be driven by the PDAR subtype. Further studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PDAR and PDT subtypes. PMID- 27266638 TI - Traumatic spinal epidural hematoma in a 1-year-old boy. AB - Traumatic spinal epidural hematoma is uncommon in children, making rapid diagnosis difficult. In this report, we present a case of traumatic cervical epidural hematoma in a 1-year-old boy, diagnosed with computed tomography scanning and magnetic resonance imaging (MRI). Management was conservative and the lesion regressed spontaneously. The presentation in childhood is often nonspecific. MRI is the imaging modality of choice for diagnosing these lesions. Conservative treatment has to be considered in cases with a benign clinical course and provided that the patient is followed up neurologically with repeated MRI. PMID- 27266639 TI - [Collagenous gastritis and colitis in a 10-year-old girl]. AB - There are few data in the literature on microscopic gastritis and colitis in the pediatric population. The diagnosis is often made after the occurrence of complications. We report the case of a 10.5 year-old girl for whom the diagnosis was made several years after the initial symptoms. Test for infections, inflammation, and auto-immunity yielded normal results. Upper endoscopy and colonoscopy revealed an abnormal mucosa. However, histology showed microscopic inflammation and fibrotic lesions in the lamina propria, and a thick subepithelial collagenous band. This led to the diagnosis of collagenous gastritis and colitis. Budesonide treatment resulted in the cessation of diarrhea and significant weight gain. Treatment by oral budesonide indeed seems to be highly effective but relapses are frequent when the treatment is stopped. This case shows the importance of being vigilant regarding transit disorders with impact on growth kinetics. Upper endoscopy and colonoscopy need to be carried out when children have organic diarrhea with normal blood tests. PMID- 27266640 TI - [Erythema nodosum due to tinea]. AB - Erythema nodosum (EN) is the most common clinical and pathological variant of panniculitis. A Celsus kerion is an inflammatory and suppurative tinea of the scalp. We report on a rare case of EN secondary to a kerion of the scalp. OBSERVATION: A 9-year-old child without a notable medical history, had a squamous plaque of the vertex for 15 days, which became painful and purulent. Five days after the plaque appeared, he presented with painful, hot, erythematous lesions symmetrically on the extensor surfaces of the legs and forearms. A medical examination found a fever of 38.5 degrees C, a squamous purulent and crusty plate of the vertex (6/5cm) with pustules and a few hairs cut short, and symmetrical painful erythematous hot nodules on the anterior surfaces of the two legs and forearms. A mycological sample of the crusts of the scalp lesion confirmed the presence of Trichophyton mentagrophytes. A bacteriological sample was not taken, and a skin biopsy confirmed the diagnosis of EN. The results of other paraclinical investigations were normal. The diagnosis of EN secondary to an inflammatory scalp tinea was established, and our patient was prescribed an orally and locally administered antimycotic, rest, and elevation of the limbs. DISCUSSION: EN is an acute nodular hypodermitis considered a nonspecific hypersensitive reaction to various allergens. Rarely, it can occur secondary to a fungal infection of the scalp such as a kerion or even secondary to the antifungal treatment of this tinea. EN secondary to a kerion of the scalp before the beginning of antifungal treatment has been reported in the literature, with a spontaneous improvement of the EN after treatment of the tinea. PMID- 27266641 TI - [Trends in vaccination coverage among children aged 12-23 months and mothers during 2006-2012 in Togo]. PMID- 27266642 TI - [Acute poisoning by pesticides in children]. AB - Acute pesticide poisoning in children is rare but potentially serious. Some clinical patterns (toxidromes) are suggestive of the drug class: cholinergic crisis for organophosphate or carbamate insecticides; neurological syndrome for rodenticides; digestive and respiratory syndrome for herbicides. Treatment is symptomatic and only a few patients are treated with an antidote: atropine and pralidoxime for organophosphate insecticides, vitamin K for anticoagulant rodenticides. PMID- 27266643 TI - Chylomicron retention disease: A rare cause of chronic diarrhea. AB - Chylomicron retention disease (CRD) is a rare autosomal recessive hereditary hypocholesterolemic disorder. The disease most frequently presents in infants and is characterized by a lipid malabsorption syndrome with steatorrhea, chronic diarrhea, and growth retardation. The disease is characterized by normal fasting serum triglyceride levels combined with the absence of apolipoprotein (apo) B48 and chylomicrons after a fat load. In this report, we describe the clinical, laboratory, and histological data as well as the molecular DNA analysis of a 12 month-old girl from Tunisia with CRD. The patient was treated with a low-fat diet and fat-soluble vitamin supplementation resulting in significant improvement. PMID- 27266644 TI - [Superior mesenteric artery syndrome or Wilkie's syndrome]. PMID- 27266645 TI - [Pediatric brucellosis : A case report and literature review]. AB - Brucellosis is an overlooked infection of widespread geographic distribution. This disease is rarely evoked when assessing unexplained pediatric fever, and only 20-30 cases (children and adults) are confirmed per year. Risk factors for contracting brucellosis are exposure to bodily fluids and consumption of unpasteurized dairy products from infected animals. Most cases of brucellosis are associated with traveling to or importing contaminated goods from endemic areas. Here, we report a case of brucellosis in a 16-month-old patient hospitalized for an acute febrile illness in a French general pediatric ward. An antibiotic regimen of rifampicin and co-trimoxazole given over 6 weeks led to successful cure without relapse. The child had eaten a cake made from unpasteurized goat's milk and imported from Oran, a region in Algeria. His mother had consumed the same cake and was hospitalized for brucellosis 15 days later. Clinicians should suspect brucellosis when encountering febrile patients who have traveled to endemic areas, been exposed to body fluids or products of abortion of farm animals, or consumed unpasteurized products. PMID- 27266646 TI - Activation of a chondrocyte volume-sensitive Cl(-) conductance prior to macroscopic cartilage lesion formation in the rabbit knee anterior cruciate ligament transection osteoarthritis model. AB - OBJECTIVE: The anterior cruciate ligament transection (ACLT) rabbit osteoarthritis (OA) model confers permanent knee instability and induces joint degeneration. The degeneration process is complex, but includes chondrocyte apoptosis and OA-like loss of cartilage integrity. Previously, we reported that activation of a volume-sensitive Cl(-) current (ICl,vol) can mediate cell shrinkage and apoptosis in rabbit articular chondrocytes. Our objective was therefore to investigate whether ICl,vol was activated in the early stages of the rabbit ACLT OA model. DESIGN: Adult Rabbits underwent unilateral ACLT and contralateral arthrotomy (sham) surgery. Rabbits were euthanized at 2 or 4 weeks. Samples were analyzed histologically and with assays of cell volume, apoptosis and electrophysiological characterization of ICl,vol. RESULTS: At 2 and 4 weeks post ACLT cartilage appeared histologically normal, nevertheless cell swelling and caspase 3/7 activity were both significantly increased compared to sham controls. In cell-volume experiments, exposure of chondrocytes to hypotonic solution led to a greater increase in cell size in ACLT compared to controls. Caspase-3/7 activity, an indicator of apoptosis, was elevated in both ACLT 2wk and 4wk. Whole-cell currents were recorded with patch clamp of chondrocytes in iso-osmotic and hypo-osmotic external solutions under conditions where Na(+), K(+) and Ca(2+) currents were minimized. ACLT treatment resulted in a large increase in hypotonic-activated chloride conductance. CONCLUSION: Changes in chondrocyte ion channels take place prior to the onset of apparent cartilage loss in the ACLT rabbit model of OA. Further studies are needed to investigate if pharmacological inhibition of ICl,vol decreases progression of OA in animal models. PMID- 27266647 TI - Spatiotemporal distribution of delta(13)CCO2 in a shallow cave and its potential use as indicator of anthropic pressure. AB - This study deals with the spatiotemporal dynamics of CO2 and its isotopic composition (delta(13)CCO2) in the atmosphere of Altamira Cave (northern Spain) over two annual cycles. In general terms, the cavity shows two distinct ventilation modes, acting as a CO2 reservoir from October to May (recharge stage), while actively exchanging gases with the outside atmosphere between July and September (discharge stage). In recharge mode, the in-cave air shows higher and relatively homogeneous CO2 values (3332 +/- 521 ppm) with lower delta(13)CCO2 (-23.2 +/- 0.40/00). In contrast, during the discharge stage, the CO2 concentrations are lower and relatively more variable (1383 +/- 435 ppm) and accompanied by higher delta(13)CCO2 (up to -120/00). This seasonal pattern is controlled by the distinct rates of exchange of air masses with the external atmosphere through the annual cycle, as well as by changes in the production of CO2 in the soil and natural fluctuations in the concentration of dissolved inorganic carbon transported by drip water into the cave. In contrast to the interpretations of previous studies in Altamira Cave, no local air intakes into the deepest cave sections were flagged by our delta(13)C measurements. This finding is also supported by analyses of CO2 and (222)Rn in air, density of airborne particles and air temperature. In addition, preliminary experiments examining the visitor-produced disturbances on delta(13)CCO2 were conducted during the various cave ventilation stages to explore the potential use of this parameter as an indicator of anthropic pressure in caves. Our data show that visits (overall stay of 60-85 min; i.e., 4 people for 20 min) significantly affected delta(13)CCO2 (up to Deltadelta(13)C ~ -20/00) in the Polychrome Hall of Altamira Cave under conditions of low natural CO2 (discharge stage), whereas it remained almost unaltered under circumstances of high CO2 concentration (recharge stage). This demonstrates that delta(13)CCO2 is sensitive to perturbations produced by visitors during certain periods. PMID- 27266648 TI - Sample size for estimating the mean concentration of organisms in ballast water. AB - We consider the computation of sample sizes for estimating the mean concentration of organisms in ballast water. Given the possible heterogeneity of their distribution in the tank, we adopt a negative binomial model to obtain confidence intervals for the mean concentration. We show that the results obtained by Chen and Chen (2012) in a different set-up hold for the proposed model and use them to develop algorithms to compute sample sizes both in cases where the mean concentration is known to lie in some bounded interval or where there is no information about its range. We also construct simple diagrams that may be easily employed to decide for compliance with the D-2 regulation of the International Maritime Organization (IMO). PMID- 27266649 TI - Lead removal from aqueous solutions by raw sawdust and magnesium pretreated biochar: Experimental investigations and numerical modelling. AB - Lead removal from aqueous solutions by raw cypress (Cupressus sempervirens L.) sawdust (RCS) and its derivative magnesium pretreated biochar (Mg-B) was investigated under static and dynamic conditions through batch and column assays. The Hydrus-1D model was used to estimate the transport parameters of the lead measured breakthrough curves. The batch experiments results showed that Mg-B was very efficient in removing lead compared to RCS and several other previously tested natural and modified materials. The column experiments results indicated that for both RCS and Mg-B, lead breakthrough curves and the related removal efficiencies were mainly dependent on the used initial concentration and the adsorbents bed height. The use of Hydrus-1D showed that the two-site chemical non equilibrium model describes better the experimental lead breakthrough curves for both RCS and Mg-B as the equilibrium model. PMID- 27266650 TI - Assessment of the risk of pollution by sulfur compounds and heavy metals in soils located in the proximity of a disused for 20 years sulfur mine (SE Poland). AB - The study assessed the long-term effects of anthropogenic pressure of the sulfur industry on turf-covered soils located in the vicinity of the sulfur mine Grzybow. The study assumes that 20 years which elapsed since the end of the exploitation of sulfur is a period sufficiently long for the content of sulfur compounds in soils not to exceed the permissible level and that soil of the region can be classified as not contaminated. A part of the study involved identification of changes in the contents Stot. and SSO4(2-) in soils collected in the 1970s and early twenty-first century. It was also traced the relationship between the content of sulfur compounds and selected soil properties and estimated risk of soil environment pollution by heavy metals. Mean contents of trace elements studied amounted to 10.2-10.8 mg kg(-1) for Pb, 14.3-39.4 mg kg( 1) for Zn, 0.2-0.4 mg kg(-1) for Cd, 3.8-32.2 mg kg(-1) for Cr, 2.7-15.1 mg kg( 1) for Cu and 2.9-18.7 mg kg(-1) for Ni. Based on the results of SSO4(2-) content in soils collected at a distance of 1 km from the mine, it was found out that despite the passage of years, the amount of this type of sulfur still is increased and exceeds 0.14 g kg(-1). As the distance from the mine grew lower (from 0.017 to 0.03 g kg(-1)) average content of the sulfur form was observed. In the studied soil material we found generally positive, strong correlation between the Stot. and SSO4(2-) content and analyzed trace elements. The degree of contamination of examined soils with heavy metals was estimated on the basis of the integrated pollution index, which pointed to a moderate and low level of antropogenization of this area. In addition, the relationship between the determined characteristics of soils (Corg. contents, the fraction <0.002 mm and pH) and heavy metals confirms that the trace elements present in soils do not occur in mobile forms in the soil solution. PMID- 27266651 TI - Case reports of aconite poisoning in mainland China from 2004 to 2015: A retrospective analysis. AB - Aconitum species have long been used in key traditional medicines in China, but cases of fatal aconite poisoning have also been reported. This paper presents a review of 40 single and multi-person cases of fatal aconite poisoning. The cases involved 53 victims in mainland China described in 27 case reports published between January 2004 and September 2015. We summarize the details of the case reports in order to highlight the features of fatal aconite-poisoning cases in China, including victims' sex and age, route of intoxication, clinical symptoms, medicolegal autopsy findings, and results of toxicological analysis. Our results indicate a need for legal medical experts encountering cases of fatal aconite poisoning to pay increased attention to the methods used for collecting biological samples. In addition, prevention strategies should focus on increasing public awareness regarding the potential toxicity of Aconitum, harm caused by medicinal liquors containing aconitine, and possibility of Aconitum alkaloids accumulating in the body. PMID- 27266652 TI - A quantitative comparison analysis of diatoms in the lung tissues and the drowning medium as an indicator of drowning. AB - The presence of diatoms in the lung tissues, internal organs and bone marrow is considered as the supportive evidence in the diagnosis of death by drowning. Generally, the diatoms detected in the lung tissues are regarded as insignificant since these diatoms can be detected in the lung tissues of the postmortem immersion bodies. In this study, we analyzed the relationships between the numbers of the diatoms in the lung tissues and the drowning medium. We made a comparison analysis between the diatoms in the lung tissues and the drowning medium using the ratio of diatom numbers in both samples (L/D ratio), utilizing Microwave Digestion - Vacuum Filtration - Automated Scanning Electron Microscopy method. Our data indicate that the L/D ratios in victims of the drowning group were higher than the postmortem immersion group. A higher L/D ratio provides valuable information about the cause of death in drowning victims. Quantitative diatom analysis in the lung tissues, especially combined with the diatom analysis of the drowning medium, provides supportive evidence in determining if a body recovered in water was due to drowning or not. PMID- 27266653 TI - Are We Missing Traumatic Bowel and Mesenteric Injuries? AB - PURPOSE: Traumatic bowel and mesenteric injury (TBMI), although an uncommon entity, can be lethal if not detected and treated in a timely manner. The purpose of our study was to evaluate the diagnostic accuracy of 64-slice multidetector computed tomography (MDCT) for the detection of TBMI in patients at our level 1 trauma centre. METHODS: We used our hospital's trauma registry to identify patients with a diagnosis of TBMI from January 1, 2006, to June 30, 2013. Only patients who had a 64-slice MDCT scan at presentation and subsequently underwent laparotomy or laparoscopy were included in the study cohort. Using the surgical findings as the gold standard, the accuracy of prospective radiology reports was analyzed. RESULTS: Of the 4781 trauma patients who presented to our institution, 44 (0.92%) had surgically proven TBMI. Twenty-two of 44 were excluded as they did not have MDCT before surgery. The study cohort consisted of 14 males and 8 females with a median age of 41.5 years and a median injury severity score of 27. In total 17 of 22 had blunt trauma and 5 of 22 had penetrating injury. A correct preoperative imaging diagnosis of TBMI was made in 14 of 22 of patients. The overall sensitivity of the radiology reports was 63.6% (95% confidence interval [CI]: 41%-82%), specificity was 79.6% (95% CI: 67%-89%), PPV was 53.9% (95% CI: 33%-73%), and the NPV was 85.5% (95% CI: 73%-94%). Accuracy was calculated at 75.3%. However, only 59% (10 of 17) of patients with blunt injury had a correct preoperative diagnosis. Review of the findings demonstrated that majority of patients with missed blunt TBMI (5 of 7) demonstrated only indirect signs of injury. CONCLUSION: The detection of TBMI in trauma patients on 64-slice MDCT can be improved, especially in patients presenting with blunt injury. Missed cases in this population occurred because the possibility of TBMI was not considered despite the presence of indirect imaging signs. The prospective diagnosis of TBMI remains challenging despite advances in CT technology and widespread use of 64 slice MDCT. PMID- 27266654 TI - Regioselective Intermolecular Diamination and Aminooxygenation of Alkenes with Saccharin. AB - Palladium catalysis enables the regioselective difunctionalization of alkenes using saccharin as the nitrogen source in the initial step of aminopalladation. Depending on the reaction conditions, diamination or aminooxygenation pathways can be accessed using hypervalent iodine reagents as the terminal oxidants. The aminooxygenation of allylic ethers originates from an unprecedented ambident behavior of saccharin. The participating palladium catalysts contain a palladium saccharide unit. Two representative complexes of this type could be isolated and characterized. PMID- 27266656 TI - Stepwise Synthesis of Bis-Alkynyl Co(III)(cyclam) Complexes under Ambient Conditions. AB - Reported herein is a new synthetic method for the synthesis of Co(III)(cyclam) bis-alkynyls (cyclam = 1,4,8,11-tetraazacyclotetradecane) under aerobic conditions. Upon the treatment of AgOTf in acetonitrile, complex trans [Co(cyclam)(C2C6H4NMe2)Cl]Cl (1) was converted to trans-[Co(cyclam)(C2C6H4NMe2) (NCMe)](OTf)2 (2), and 2 was in turn reacted with HC2Ar under weakly basic conditions to afford the novel bis-alkynyls trans [Co(cyclam)(C2C6H4NMe2)(C2Ar)](OTf) (Ar = C6H4NMe2 (3) and C6F5 (4)) in reasonable yields. Voltammetric analysis revealed a modest NMe2/NMe2 coupling across the Co-alkynyl backbone in 3, while DFT calculations identified the HOMO in 3 as the superexchange pathway for such coupling. PMID- 27266655 TI - Metals from mine waste as potential cause of oxidative stress in burrowing crab Neohelice granulata from San Antonio bay. AB - The Natural Protected Area San Antonio bay is of particular importance for its congregation of migratory shorebirds and it has been declared one of the Western Hemisphere Shorebird Reserve Network International site (WHSRN). Present study represents the first assessment of variation on oxidative stress biomarkers in male crab Neohelice granulata from San Antonio bay (Rio Negro, Argentina) under field conditions, associated mainly to metal contamination coming from passive mining wastes. Three sites were sampled once every three months from November 2012 to August 2013 within this sea inlet (Pile, Fishery and Port) and a control site at the southeast of the bay (Punta Perdices). Accumulation of Ni, Zn, Cr and Al varied only with seasons although without a constant trend, meanwhile Cd, Cu and Pb also varied among sites being highest in Pile and Port. Biochemical results indicated that variations in catalase activity was only site specific being maximum in Pile; meanwhile lipid radical, alpha-tocopherol and metallothioneins were only seasonal specific being higher in autumn and winter. Seasonal variation was also found for total thioles, being the content higher in summer and autumn than in winter. Correlation analysis revealed that malondialdehyde and alpha-tocopherol have a positive association with Al and negative with Ni, meanwhile GST has a positive association with Fe. Crabs from the closest area to the waste pile did not exhibit a differentiated oxidative pressure despite the higher accumulation of metals. It is possible that crabs from contaminated areas have developed a tolerance to metals, indicating a strong ecotoxicological selective pressure. More studies are needed to assess whether there is a transfer of metals through the food chain. PMID- 27266657 TI - Dual FITC lateral flow immunoassay for sensitive detection of Escherichia coli O157:H7 in food samples. AB - A pattern of signal amplification lateral flow immunoassay (LFIA) for pathogen detection, which used fluorescein isothiocyanate (FITC) labeled antigen and antibody for dual FITC-LFIA was developed. Escherichia coli O157:H7 (E.coli O157:H7) was selected as the model analyte. In the signal amplification LFIA method, FITC was mixed with sample culture medium, with the presence of E.coli O157:H7 in the samples, the bacteria could emit a yellow-green fluorescence after incubation, creating a fluorescent antigen probe. This antigen probe was added to LFIA, which already contained E.coli O157:H7 monoclonal antibodies-FITC (McAb E.coli O157:H7-FITC) dispersed in the conjugate pad. Another E.coli O157:H7 McAb was the test line, and goat anti-mouse IgG antibody was the control line in nitrocellulose (NC) membrane. The visual limit of detection (LOD) of the strip for qualitative detection was 10(5) CFU/mL while the LOD for semi-quantitative detection could down to 10(4) CFU/mL by using scanning reader. Signal amplification LFIA was perfectly applied to the detection of food samples with E.coli O157:H7. The LOD was substantially improved to 1 CFU/mL of the original bacterial content after pre-incubation of the bread, milk and jelly samples in broth for 10, 8 and 8h respectively. The results of this method was more sensitive by 10-fold than the conventional colloidal gold (CG) based strips and comparable to the traditional ELISA. This simple, low-cost and easy to be popularized method served as a significant step towards the development of monitoring food-borne pathogens in food-safety testing. PMID- 27266658 TI - Molecularly imprinted polymer-based bulk optode for the determination of itopride hydrochloride in physiological fluids. AB - We report here for the first time on the use of Molecularly Imprinted Polymers as modifiers in bulk optodes, Miptode, for the determination of a pharmaceutical compound, itopride hydrochloride as an example in a concentration range of 1*10( 1)-1*10(-4)molL(-1). In comparison to the optode containing the ion exchanger only (Miptode 3), the optode containing the ion exchanger and the MIP particles (Miptode 2) showed improved selectivity over the most lipophilic species, Na(+) and K(+), by more than two orders of magnitude. For instance, the optical selectivity coefficients using Miptode 2, [Formula: see text] , were as follow: NH4(+)?-6; Na(+)=-4.0, which were greatly enhanced in comparison with that obtained by Miptode 3. This work opens a new avenue for using miptodes for the determination of all the pharmaceutical preparations without the need for the development of new ionophores. PMID- 27266659 TI - 4-mercaptophenylboronic acid functionalized gold nanoparticles for colorimetric sialic acid detection. AB - A simple and selective colorimetric sensor for sialic acid detection, based on the aggregation of 4-mercaptophenylboronic acid functionalized gold nanoparticles (4-MPBA-AuNPs) was developed. The color of the solution changed from wine-red to blue after binding with sialic acid. The colorimetric sensor provided good analytical performances with a linear dynamic range of 80uM to 2.00mM and a 68+/ 2uM limit of detection without any effect from possible interferences and sample matrix. In addition, the quantitative results were obtained within only 10min. This developed sensor was used to detect sialic acid in blood serum samples and the results were in good agreement with those from the current periodate resorcinol method (P>0.05) thus indicating that this developed colorimetric sensor can be used as an alternative method for sialic acid detection with a shorter analysis time and a high accuracy. PMID- 27266660 TI - Atomic force microscopy combined with human pluripotent stem cell derived cardiomyocytes for biomechanical sensing. AB - Cardiomyocyte contraction and relaxation are important parameters of cardiac function altered in many heart pathologies. Biosensing of these parameters represents an important tool in drug development and disease modeling. Human embryonic stem cells and especially patient specific induced pluripotent stem cell-derived cardiomyocytes are well established as cardiac disease model.. Here, a live stem cell derived embryoid body (EB) based cardiac cell syncytium served as a biorecognition element coupled to the microcantilever probe from atomic force microscope thus providing reliable micromechanical cellular biosensor suitable for whole-day testing. The biosensor was optimized regarding the type of cantilever, temperature and exchange of media; in combination with standardized protocol, it allowed testing of compounds and conditions affecting the biomechanical properties of EB. The studied effectors included calcium , drugs modulating the catecholaminergic fight-or-flight stress response such as the beta adrenergic blocker metoprolol and the beta-adrenergic agonist isoproterenol. Arrhythmogenic effects were studied using caffeine. Furthermore, with EBs originating from patient's stem cells, this biosensor can help to characterize heart diseases such as dystrophies. PMID- 27266661 TI - A sensitive spectrofluorometric method for detection of berberine hydrochloride using Ag nanoclusters directed by natural fish sperm DNA. AB - A novel DNA-directed AgNCs (DNA-AgNCs) was synthesized with economical raw material (natural fish sperm DNA) through a simple and rapid approach, and it first showed high and stable fluorescence emission as a AgNCs stabilized by natural DNA at about 635nm. Moreover, its emission intensity could be enhanced tremendously in acetic acid (HAc) medium. Whereas, when berberine hydrochloride (BRH) entered the solution system, it would interact and combine efficiently with DNA on the surface of AgNCs, which could lead to subtle change of charge distribution on its surface, and make it more lyophobic, inducing aggregation of DNA-AgNCs. As a result, fluorescence of the system was quenched visually; the process represented a color variance from yellow to hot pink under HAc medium, then back to yellowish-brown when BRH worked. Based on above phenomenon, a selective and accurate spectrofluorometric method for BRH detection was established. It can be applied to detect trace amounts of BRH in aqueous solution in the linear range from 1.0nM to 2000.0nM; and the detection limit (3sigma/k) was 0.3nM, which is pretty lower compared to most reported spectral methods. Simultaneously, a semi-quantitative determination by visual evaluation from 5.0nM to 2000.0nM was also achieved. This method provided excellent selectivity for the detection of BRH in the presence of ten kinds of common natural amino acids and nine kinds of common mental ions. Furthermore, the BRH content in compound berberine tablets from drugstore was successfully investigated by this method and the results showed high accuracy. PMID- 27266663 TI - The traditional food of migrants: Meat, water, and other challenges for dietary advice. An ethnography in Guanajuato, Mexico. AB - The term "traditional diet" is used variously in public health and nutrition literature to refer to a substantial variety of foodways. Yet it is difficult to draw generalities about dietary tradition for specific ethnic groups. Given the strong association between migration and dietary change, it is particularly important that dietary advice for migrants be both accurate and specific. In this article, I examine the cultural construct of "traditional foods" through mixed method research on diet and foodways among rural farmers in Guanajuato, MX and migrants from this community to other Mexican and U.S. destinations. Findings reveal first, that quantitatively salient terms may contain important variation, and second, that some "traditional" dietary items -like "refresco," "carne," and "agua" - may be used in nutritionally contradictory ways between clinicians and Mexican immigrant patients. Specifically, the term "traditional food" in nutritional advice for Mexican migrants may be intended to promote consumption of fresh produce or less meat; but it may also invoke other foods (e.g., meats or corn), inspire more regular consumption of formerly rare foods (e.g., meats, flavored waters), or set up financially impossible goals (e.g., leaner meats than can be afforded). Salience studies with ethnographic follow up in target populations can promote the most useful and accurate terms for dietary advice. PMID- 27266662 TI - Burst-suppression is reactive to photic stimulation in comatose children with acquired brain injury. AB - OBJECTIVE: Burst-suppression is an electroencephalographic pattern observed during coma. In individuals without known brain pathologies undergoing deep general anesthesia, somatosensory stimulation transiently increases the occurrence of bursts. We investigated the reactivity of burst-suppression in children with acquired brain injury. METHODS: Intensive care unit electroencephalographic monitoring recordings containing burst-suppression were obtained from 5 comatose children with acquired brain injury of various etiologies. Intermittent photic stimulation was performed at 1Hz for 1min to assess reactivity. We quantified reactivity by measuring the change in the burst ratio (fraction of time in burst) following photic stimulation. RESULTS: Photic stimulation evoked bursts in all patients, resulting in a transient increase in the burst ratio, while the mean heart rate remained unchanged. The regression slope of the change in burst ratio, referred to as the standardized burst ratio reactivity, correlated with subjects' Glasgow Coma Scale scores. CONCLUSIONS: Reactivity of the burst-suppression pattern to photic stimulation occurs across diverse coma etiologies. Standardized burst ratio reactivity appears to reflect coma severity. SIGNIFICANCE: Measurement of burst ratio reactivity could represent a simple method to monitor coma severity in critically ill children. PMID- 27266664 TI - Predictors of binge eating in male and female youths in the United Arab Emirates. AB - OBJECTIVE: Binge eating is a health-risk behavior associated with obesity, eating disorders and many other diseases. However, binge eating research remains narrow especially in Arab countries where obesity is a primary health concern but studies on psychological factors of compulsive overeating are rare. The present study addressed this gap by examining prevalence rates and key predictors of binge eating among youths in the United Arab Emirates (UAE). METHOD: Binge eating was assessed together with stress levels, emotional eating, body-related shame and guilt, obsessive-compulsiveness and depression in 254 youths using standardized self-report measures. The study comprised three online-based assessments over a 3-month period. RESULTS: Moderate to severe binge eating was reported by one-third of participants. Emotional eating and body-related guilt were the most consistent and powerful positive binge eating predictors. While stress levels and body-related shame were statistically significant predictors at follow up, neither obsessive-compulsiveness nor depressive symptomatology predicted binge eating in this study. DISCUSSION: Findings highlight binge eating as a common concern among youths in the UAE with prevalence rates similar to Western samples. Furthermore, the data suggest that binge eating may operate as a maladaptive coping strategy by alleviating negative emotions including boredom and loneliness. The finding that body-related guilt predicted binge eating is important as until now inconsistencies persist as to the relationship between body-related guilt and eating pathology. The study points towards multifactorial risk and maintenance factors of binge eating and extends our understanding within a population where until now research is poor. PMID- 27266665 TI - Ethanol downregulates N-acyl phosphatidylethanolamine-phospholipase D expression in BV2 microglial cells via epigenetic mechanisms. AB - Excessive ethanol drinking has deleterious effects on the brain. However, the effects of alcohol on microglia, the main mediator of the brain's innate immune response remain poorly understood. On the other hand, the endocannabinoid system plays a fundamental role in regulating microglial reactivity and function. Here we studied the effects of acute ethanol exposure to murine BV2 microglial cells on N-acyl phosphatidylethanolamine-phospholipase D (NAPE-PLD), a major synthesizing enzyme of anandamide and other N-acylethanolamines. We found that ethanol downregulated microglial NAPE-PLD expression by activating cAMP/PKA and ERK1/2. These signaling pathways converged on increased phosphorylation of CREB. Moreover, ethanol induced and increase in histone acetyltransferase activity which led to higher levels of acetylation of histone H3. Taken together, our results suggest that ethanol actions on microglial NAPE-PLD expression might involve epigenetic mechanisms. PMID- 27266666 TI - Antinociceptive effect of clinical analgesics in a nonhuman primate model of knee osteoarthritis. AB - A number of potential analgesic pharmacotherapies developed in preclinical osteoarthritis animal models have failed clinical trials. A possible basis for the lack of translation of preclinical findings to clinical efficacy is the use of a preclinical species that is distinct from that of humans. The current study tested clinical analgesics in a nonhuman primate model of knee osteoarthritis. Following a medial meniscectomy, the animals developed a robust ipsilateral reduction in knee pressure threshold (hyperalgesia) and an ipsilateral reduction in weight bearing (resting pain). The serotonin-noradrenalin reuptake inhibitor duloxetine and opioid morphine increased ipsilateral pressure threshold and weight bearing. By contrast, the anticonvulsant pregabalin did not affect either pressure hyperalgesia or resting pain. The current findings in the nonhuman primate model of osteoarthritis parallel clinical findings, in that duloxetine and opioids are used in the management of osteoarthritis pain whereas pregabalin is not. The current findings also suggest the possible differentiation of pharmacotherapeutics in a nonhuman primate model, of distinguishing potential clinically useful analgesics for the management of osteoarthritic pain from those that are not. PMID- 27266668 TI - 2,2'-Fluorine mono-carbonyl curcumin induce reactive oxygen species-Mediated apoptosis in Human lung cancer NCI-H460 cells. AB - In this paper, we synthesized three fluorine-substituted mono-carbonyl curcumin analogs and evaluated their cytotoxicity against several cancer cells by the MTT assay. The results exhibited that all the three compounds were more active than the leading curcumin. Especially, 2,2'-F mono-carbonyl curcumin, 1a, surfaced as an important lead compound displaying almost 4-fold cytotoxicity relative to curcumin. More importantly, 1a was more stable in (RPMI)-1640 medium and more massive uptake than curcumin, which may be relationship to their cytotoxicity, apoptotic acitivity and reactive oxygen species generation. And then, the generation of reactive oxygen species can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 2,2'-F mono-carbonyl curcumin (1a) may cause cancer cells apoptosis through reactive oxygen species-Mediated pathway, but also gives us an important information for design of mono-carbonyl curcumin analog. PMID- 27266667 TI - Preventive and alleviative effects of the dual enkephalinase inhibitor (Denki) PL265 in a murine model of neuropathic pain. AB - Neuropathic pain remains difficult to treat due to the involvement of various pathophysiological mechanisms in its pathogeny. Among the different opioidergic systems the enkephalinergic one is primarily recruited via activation of delta opioid receptor (DOP) in chronic pain and of mu opioid receptor (MOP) in acute pain. To investigate the role of their endogenous ligands Met and Leu-enkephalin in neuropathic pain control, a dual inhibitor of their degrading enzymes, PL265, which acts restrictively at the level of peripheral nociceptors, was administered per os to assess its efficacy in pain prevention and alleviation using a partial sciatic nerve ligation model (PSNL) in mice. We demonstrated here that the pre injury oral administration of PL265 (50mg/kg) during the 9 days of neuropathy development reduces thermal hyperalgesia and mechanical allodynia for two weeks after the end of treatment. The repeated administration (50mg/kg daily, during 10 days) does not induce tolerance. Therefore, protecting the enkephalins released at the peripheral level during neuropathic pain with oral PL265 seems to be a promising approach to prevent and alleviate the painful symptoms of neuropathic pain in humans without the unwanted effects of exogenous opiates such as morphine. PMID- 27266669 TI - Cooperative N-Heterocyclic Carbene/Palladium-Catalyzed Enantioselective Umpolung Annulations. AB - A combination of NHC organocatalysis and transition-metal catalysis gives rise to fundamentally new cooperative reactivity and enables the regio- and enantioselective annulation reaction between enals and vinyl benzoxazinanones. The cooperative umpolung annulation eliminates mutual deactivation and leads to a diverse set of benzazepine derivatives in good yields with excellent enantioselectivities (up to 99% ee). The development of such a cooperative catalytic system dramatically expands the scope of NHC organocatalysis by opening up new metal-catalyzed reaction pathways for homoenolate intermediates. PMID- 27266670 TI - Gas-Phase Reactions of Atomic Gold Cations with Linear Alkanes (C2-C9). AB - To develop proper ionization methods for alkanes, the reactivity of bare or ligated transition metal ions toward alkanes has attracted increasing interests. In this study, the reactions of the gold cations with linear alkanes from ethane up to nonane (CnH2n+2, n = 2-9) under mild conditions have been characterized by mass spectrometry and density functional theory calculations. When reacting with Au(+), small alkanes (n = 2-6) were confirmed to follow specific reaction channels of dehydrogenation for ethane and hydride transfer for others to generate product ions characteristic of the original alkanes, which indicates that Au(+) can act as a reagent ion to ionize alkanes from ethane to n-hexane. Strong dependence of the chain length of alkanes was observed for the rate constants and reaction efficiencies. Extensive fragmentation took place for larger alkanes (n > 6). Theoretical results show that the fragmentation induced by the hydride transfer occurs after the release of AuH. Moreover, the fragmentation of n-heptane was successfully avoided when the reaction took place in a high-pressure reactor. This implies that Au(+) is a potential reagent ion to ionize linear and even the branched alkanes. PMID- 27266671 TI - Evolutionary dynamics of cytoplasmic segregation and fusion: Mitochondrial mixing facilitated the evolution of sex at the origin of eukaryotes. AB - Sexual reproduction is a trait shared by all complex life, but the complete account of its origin is missing. Virtually all theoretical work on the evolution of sex has been centered around the benefits of reciprocal recombination among nuclear genes, paying little attention to the evolutionary dynamics of multi-copy mitochondrial genomes. Here I develop a mathematical model to study the evolution of nuclear alleles inducing cell fusion in an ancestral population of clonal proto-eukaryotes. Segregational drift maintains high mitochondrial variance between clonally reproducing hosts, but the effect of segregation is opposed by cytoplasmic mixing which tends to reduce variation between cells in favor of higher heterogeneity within the cell. Despite the reduced long-term population fitness, alleles responsible for sexual cell fusion can spread to fixation. The evolution of sex requires negative epistatic interactions between mitochondrial mutations under strong purifying selection, low mutation load and weak mitochondrial-nuclear associations. I argue that similar conditions could have been maintained during the late stages of eukaryogenesis, facilitating the evolution of sexual cell fusion and meiotic recombination without compromising the stability of the emerging complex cell. PMID- 27266672 TI - Literal grid map models for animal navigation: Assumptions and predictions. AB - Many animals can navigate from unfamiliar locations to a familiar target location with no outward route information or direct sensory contact with the target or any familiar landmarks. Several models have been proposed to explain this phenomenon, one possibility being a literal interpretation of a grid map. In this paper we systematically compare four such models, which we label: Correct Bicoordinate navigation, both Target and Release site based, Approximate Bicoordinate navigation, and Directional navigation. Predictions of spatial patterns of initial orientation errors and efficiencies depend on a combination of assumptions about the navigation mechanism and the geometry of the environmental coordinate fields used as model inputs. When coordinates axes are orthogonal at the target the predictions from the Correct Bicoordinate (Target based) model and Approximate Bicoordinate model are identical. However, if the coordinate axes are non-orthogonal different regional patterns of initial orientation errors and efficiencies can be expected from these two models. Field anomalies produce high magnitudes of orientation errors close to the target, while region-wide nonlinearity leads to orientation errors increasing with distance from the target. In general, initial orientation error patterns are more useful for distinguishing between different assumption combinations than efficiencies. We discuss how consideration of model predictions may be helpful in the design of experiments. PMID- 27266674 TI - Coherent Coupling of WS2 Monolayers with Metallic Photonic Nanostructures at Room Temperature. AB - Room temperature strong coupling of WS2 monolayer exciton transitions to metallic Fabry-Perot and plasmonic optical cavities is demonstrated. A Rabi splitting of 101 meV is observed for the Fabry-Perot cavity. The enhanced magnitude and visibility of WS2 monolayer strong coupling is attributed to the larger absorption coefficient, the narrower line width of the A exciton transition, and greater spin-orbit coupling. For WS2 coupled to plasmonic arrays, the Rabi splitting still reaches 60 meV despite the less favorable coupling conditions, and displays interesting photoluminescence features. The unambiguous signature of WS2 monolayer strong coupling in easily fabricated metallic resonators at room temperature suggests many possibilities for combining light-matter hybridization with spin and valleytronics. PMID- 27266673 TI - Skeletal muscle mass and body fat in relation to successful ageing of older adults: The multi-national MEDIS study. AB - BACKGROUND: The determinants that promote successful ageing still remain unknown. The aim of the present work was to evaluate the role of skeletal muscle mass and body fat percentage (BF%), in the level of successful ageing. METHODS: during 2005-2011, 2663 older (aged 65-100 years) from 21 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled in the study. Appendicular skeletal muscle mass (ASM), skeletal muscle mass index (SMI) and BF% were calculated using population formulas. Dietary habits, energy intake, expenditure and energy balance were derived throughout standard procedures. A successful ageing index ranging from 0 to 10 was used. RESULTS: The mean ASM mass was 24+/-6.0kg, the SMI was 0.84+/-0.21 and the BF% was 44%. Females had lower SMI and higher BF% in comparison with males, respectively [(SMI: 0.66+/-0.09 vs. 1.03+/-0.11; BF%: 51% vs. 34%, (p<0.001)]. High successful agers had better rates in ASM (p=0.01), SMI (p<0.001) and BF% (p<0.001), compared with the medium and low successful ones. Changes in SMI [b-coefficient (95% CI):2.14 (1.57 to 2.71)] were positively associated with successful ageing, while changes in BF% [b coefficient (95% CI): -0.04 (-0.05 to -0.03)] were inversely associated with successful ageing. Results from sensitivity analysis showed that the effects of variations on body composition were consistent, less pronounced in the positive energy balance group and more pronounced among the oldest old. CONCLUSIONS: Body composition changes seem to be associated with lower quality of life in the older adults, as measured through successful ageing. PMID- 27266675 TI - How do I best manage insomnia and other sleep disorders in older adults with cancer? AB - Insomnia is common in older adults with cancer, with a reported prevalence of 19 60% in prior studies. Cancer treatments are associated with increased risk of insomnia or aggravation of pre-existing insomnia symptoms, and patients who are receiving active cancer treatments are more likely to report insomnia. Insomnia can lead to significant physical and psychological consequences with increased mortality. We discuss physiological sleep changes in older adults, and illustrated the various sleep disorders. We present a literature review on the prevalence and the effects of insomnia on the quality of life in older adults with cancer. We discuss the risk factors and presented a theoretical framework of insomnia in older adults with cancer. We present a case study to illustrate the assessment and management of insomnia in older adults with cancer, comparing and contrasting a number of tools for sleep assessment. There are currently no guidelines on the treatment of sleep disorders in older adults with cancer. We present an algorithm developed at the City of Hope Comprehensive Cancer Center by a multidisciplinary team for managing insomnia, using evidence-based pharmacologic and non-pharmacologic interventions. PMID- 27266676 TI - Countdown to the 2016 Olympic Games: A travel medicine checklist. PMID- 27266677 TI - Online cognition: factors facilitating reliable online neuropsychological test results. AB - OBJECTIVE: Online neuropsychological test batteries could allow for large-scale cognitive data collection in clinical studies. However, the few online neuropsychological test batteries that are currently available often still require supervision or lack proper psychometric evaluation. In this paper, we have outlined prerequisites for proper development and use of online neuropsychological tests, with the focus on reliable measurement of cognitive function in an unmonitored setting. METHOD: First, we identified several technical, contextual, and psychological factors that should be taken into account in order to facilitate reliable test results of online tests in the unmonitored setting. Second, we outlined a methodology of quality assurance needed in order to obtain reliable cognitive data in the long run. RESULTS: Based on factors that distinguish the online unmonitored test setting from the traditional face-to-face setting, we provide a set of basic requirements and suggestions for optimal development and use of unmonitored online neuropsychological tests, including suggestions on acquiring reliability, validity, and norm scores. CONCLUSIONS: When properly addressing factors that could hamper reliable test results during development and use, online neuropsychological tests could aid large-scale data collection for clinical studies in the future. Investment in both proper development of online neuropsychological test platforms and the performance of accompanying psychometric studies is currently required. PMID- 27266678 TI - Electrochemical Ion Transfer with Thin Films of Poly(3-octylthiophene). AB - We report on the limiting conditions for ion-transfer voltammetry between an ion exchanger doped and plasticized poly(vinyl chloride) (PVC) membrane and an electrolyte solution that was triggered via the oxidation of a poly(3 octylthiophene) (POT) solid-contact (SC), which was unexpectedly related to the thickness of the POT SC. An electropolymerized 60 nm thick film of POT coated with a plasticized PVC membrane exhibited a significant sodium transfer voltammetric signal whereas a thicker film (180 nm) did not display a measurable level of ion transfer due to a lack of oxidation of thick POT beneath the membrane film. In contrast, this peculiar phenomenon was not observed when the POT film was in direct contact with an organic solvent-based electrolyte. This evidence is indicative of three key points: (i) the coated membrane imposes a degree of rigidity to the system, which restricts the swelling of the POT film and its concomitant p-doping; (ii) this phenomenon is exacerbated with thicker POT films due to an initial morphology (rougher comprising a network of large POT nanoparticles), which gives rise to a diminished surface area and electrochemical reactivity in the POT SC; (iii) the rate of sodium transfer is higher with a thin POT film due to a smoother surface morphology made up of a network of smaller POT nanoparticles with an increased surface area and electrochemical reactivity. A variety of techniques including cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), ellipsometry, scanning electron microscopy (SEM), atomic force microscopy (AFM), and synchrotron radiation-X-ray photoelectron spectroscopy (SR-XPS) were used to elucidate the mechanism of the POT thickness/POT surface roughness dependency on the electrochemical reactivity of the PVC/POT SC system. PMID- 27266679 TI - Water Diffusion Dependence on Amphiphilic Block Design in (Amphiphilic Hydrophobic) Diblock Copolymer Membranes. AB - Polyelectrolyte membranes (PEMs) are applied in polyelectrolyte fuel cells (PEFC). The proton conductive pathways within PEMs are provided by nanometer sized water containing pores. Large-scale application of PEFC requires the production of low-cost membranes with high proton conductivity and therefore good connected pore networks. Pore network formation within four alternative model diblock (hydrophobic_amphiphilic) copolymers in the presence of water is studied by dissipative particle dynamics. Each hydrophobic block contains 50 consecutively connected hydrophobic (A) fragments, and amphiphilic blocks contain 40 hydrophobic A beads and 10 hydrophilic C beads. For one amphiphilic block the C beads are distributed uniformly along the backbone. For the other architectures C beads are located at the end of the side chains attached at regular intervals along the backbone. Water diffusion through the pores is modeled by Monte Carlo tracer diffusion through mapped morphologies. Diffusion is highest for the grafted architectures and increases with increase of length of the side chains. A consistent picture emerges in which diffusion strongly increases with the value of ?Nbond? within the amphiphilic block, where ?Nbond? is the average number of bonds between hydrophobic A beads and the nearest C bead. PMID- 27266680 TI - [Application of extracorporeal membrane oxygenation for the donor organ function maintenance]. PMID- 27266681 TI - [Effectiveness and safety of conversion therapy with the combination of sirolimus with low dose cyclosporine in renal transplantation recipients: a five-year clinical observation]. AB - OBJECTIVE: To assess the effectiveness and safety of the conversion therapy from traditional cyclosporine (CsA) triple immunosuppression therapy to sirolimus (SRL) combined with low dose CsA and prednisone (Pred) in renal transplantation recipients in a five-year follow-up period. METHODS: A prospective, open-label non-randomized study was performed with 46 renal allograft recipients who visited Tongji Hospital regularly for follow-up visits between January 2007 and May 2011 and were taking CsA+ mycophenolate mofetil (MMF)+ Pred. Conversion therapy to SRL+ low dose CsA+ Pred was initiated after renal transplantation. The recipients were allocated to 2 groups according to their renal function and proteinuria before the conversion: active conversion group [n=27, serum creatinine (SCr) <= 140 MUmol/L with no or minimal proteinuria] and passive conversion group [n=19, SCr>140 MUmol/L with less than moderate proteinuria]. After conversion, dosages of SRL and CsA were adjusted for trough levels of 5-7 MUg/L and 20-60 MUg/L, respectively. SCr and urine protein were compared before and after the conversion in five-year follow-up. Incidence of acute rejection, renal graft survival and SRL-related adverse effects of the immunosuppressive regimen were also observed. RESULTS: After conversion, an average 63% dose reduction of CsA was achieved in all the patients. In the active conversion group, the mean SCr level was (110+/ 19) MUmol/L at the time of conversion. Eight patients in this group withdrew from the study during the follow-up period for the following reasons: arthralgia (1 case), deteriorated proteinuria (2 cases), chronic diarrhea (2 cases), mild or suspicious acute rejection (2 cases), and recurrent fever (1 case). The rest patients (19/27) with a mean follow-up time of 5 years had a stable SCr level [(103+/-12) MUmol/L] and a 100% 5-year graft survival. In the passive conversion group, the mean SCr level was (205+/-45) MUmol/L at the time of conversion. There were 4 patients quitting the study, 2 for deteriorated proteinuria and 2 for lost to follow-up. Chronic allograft failure developed in 10 patients in this group 1 50 months after conversion, while the remaining 5 patients had a stable SCr during the 5-year follow-up period [(218 +/-46) MUmol/L before conversion vs (205+/-73) MUmol/L 5 years after conversion]. The overall 5-year graft survival after the conversion therapy in the passive conversion group was 33.3%, significantly lower than that of the active conversion group (P<0.001). Acute rejection was observed in 2 cases in the active conversion group, while not observed in the passive conversion group. None of the patients developed leukopenia, thrombocytopenia, oral ulcer, or pneumonia in the follow-up. CONCLUSIONS: The combination therapy of SRL and low dose of CsA is overall a safe and effective maintenance immunosuppressive regimen, but it is important to initiate at an appropriate stage. More favourable long-term benefits may be obtained from the conversion therapy in patients with normal or only slightly impaired renal graft function. It may offer an option of individualized immunosuppressive therapy after renal transplantation. PMID- 27266682 TI - [Expression and significance of neutrophil surface adhesion molecules in renal transplant recipients with cytomegalovirus infection]. AB - OBJECTIVE: To study the expression and its diagnostic significance of neutrophil surface adhesion molecules including CD11b, CD15 and CD62L after renal transplantation in recipients with cytomegalovirus (CMV) infection. METHODS: Blood samples were collected from 142 kidney transplant recipients, including 95 males and 47 females, who received allogeneic renal transplantation between September 2009 and January 2015 in 309th Hospital of the PLA. Healthy volunteers (22 males and 9 females) were recruited from physical examination center in 309th Hospital of the PLA from September 2009 to January 2015 as healthy control group. Renal transplant recipients were divided into high active CMV infection group, active CMV infection group and CMV negative control group according to CMV-pp65 antigen detection. Neutrophil surface adhesion molecules CD11b, CD15 and CD62L were detected by flow cytometry and their mean fluorescence intensity compared among the groups. Receiver operating characteristic (ROC) curves of CD11b, CD15 and CD62L in detecting active infection in renal transplant recipients were made. RESULTS: The mean fluorescence intensity of CD15 in high active CMV infection group(n=17) and active CMV infection group(n=65)were 776.31+/-89.53 and 554.39+/ 67.89, respectively, with significant differences compared with CMV negative control group (n=60, 334.92+/-44.69) and healthy control group (n=31, 310.56+/ 39.67) (all P<0.05); the expression proportions of CD11b and CD62L in high active CMV infection group and were 42.31%+/-6.11% and 40.35%+/-6.47%, respectively, with significant differences compared with active CMV infection group(62.45%+/ 5.67% and 65.65%+/-5.33%), CMV negative control group(70.74%+/-6.55% and 70.37%+/ 6.71%) and healthy control group(72.52%+/-6.48% and 72.43%+/-6.51%) (all P<0.05). The optimal cut-off values of CD11b and CD62L in diagnosing active CMV infection group were 56.61% and 44.35%, respectively, with the sensitivity being both 100.00%, the specificity being 76.67% and 58.06% respectively, and the area under the curve (AUC) being 0.851 and 0.628 respectively; the optimal cut-off values of CD11b and CD62L in diagnosing high active CMV infection group were 66.57% and 69.56% respectively, with the sensitivity being 81.54% and 87.69% respectively, the specificity being 100.00% and 98.33% respectively, and the AUC being 1.000 and 0.991 respectively; the optimal cut-off values of mean fluorescence intensity of CD15 in diagnosing high active CMV infection group and active CMV infection group were 542.71 and 408.03 respectively, the sensitivity in the two groups being 100.00% and 98.46% respectively, the specificity being both 100.00%, and the AUC being 1.000 and 0.999 respectively. CONCLUSIONS: Neutrophils CD15 expression may be up-regulated in renal transplantation recipients with CMV infection, while neutrophils CD11b and CD62L expressions are down-regulated. Such changes in CD15, CD11b and CD62L expression can be used as a basis for laboratory diagnosis of active CMV infection. PMID- 27266683 TI - [Clinical analysis on effect of retroperitoneoscopic nephrectomy in elderly donors for renal transplantation]. AB - OBJECTIVE: To evaluate the safety and effectiveness of retroperitoneoscopic donor nephrectomy in elderly donors for renal transplantation. METHODS: A retrospective analysis was conducted with 123 cases of retroperitoneoscopic living donor kidney transplantation in 309th Hospital of PLA from March 2011 to March 2014, including 44 elderly donors (age>=55 years) and 79 young to middle-aged donors (age <55 years). Comparisons were made in terms of postoperative complications in both donors and recipients, renal function recovery in the donors and function of graft in the recipients. RESULTS: The clinical baseline data of the two groups shows that glomerular filtration rate (GFR) of donors in the elderly donor group was lower than the young donor group (P=0.04). The 123 donors all underwent retroperitoneoscopic donor nephrectomy successfully. Postoperative complications in donors and recipients of both groups had no significant differences (P=0.60; P=1.00). In the elderly donor group, the mean serum creatinine level of donors was significantly higher than that in the young donors group [(115.8+/-22.3) vs (102.5+/-16.3) MUmol/L, P<0.01] 3 days after operation; and estimated GFR (eGFR) was lower [(53.0+/-9.1)vs(59.6+/-8.3)ml.min(-1).(1.73 m(2))(-1,) P<0.01]. Serum creatinine and eGFR of the two groups showed no significant differences one week and six months after surgery (all P>0.05). Four recipients in the elderly donor group had delayed graft function (DGF), 3 had acute rejection; 8 recipients in the young donor group had DGF, 5 had acute rejection; no statistically significant differences were observed between the 2 groups (both P=1.00). Recipients' eGFR were higher in the young donor group than in the elderly donor group at 1 week, 1 month, 3 months, 6 months and 12 months after surgery, but with no statistically significant differences(all P>0.05). After (27.8+/-12.6) months follow-up, 1 recipient in the elderly donor group died from pulmonary infection; two recipients in the young donor group had kidney dysfunction. Graft survival in the two groups showed no significant difference(P=0.95). CONCLUSIONS: Retroperitoneoscopic donor nephrectomy is safe and feasible for elderly donors. With careful preoperative evaluation, precise operation, and close postoperative monitoring and follow-up, it could provide satisfactory clinical outcome. PMID- 27266684 TI - [Massive hemorrhage caused by fungal infections after donation-after-cardiac death kidney transplantation: clinical features, prevention and treatment experience]. AB - OBJECTIVE: To study the characteristics and prevention and treatment strategies of massive hemorrhage caused by fungal infections after donation-after-cardiac death (DCD) kidney transplantation. METHODS: A total of 91 cases of DCD kidney transplantation between August 25, 2013 and June 30, 2015 in Third Affiliated Hospital of Sun Yat-sen Univservity were retrospectively analyzed. The characteristics of and prevention and treatments strategies for postoperative massive hemorrhage caused by fungal infections were summarized. RESULTS: Ninety one cases of DCD kidney transplantation were divided into 2 groups based on regimens for preventing postoperative fungal infections: fluconazole prophylaxis group: a total of 26 cases of renal transplant before June 11, 2014 received fluconazole regimen, from postoperative day 0 to 2 weeks; micafungin prophylaxis group: a total of 65 cases of renal transplant after June 11, 2014 received micafungin regimen, also for 2 weeks from postoperative day 0. Two cases in fluconazole group developed postoperative massive hemorrhage. In case 1, the hemorrhage occurred at 2 weeks after transplantation. Graft nephrectomy was performed during surgical exploration for hemostasis, yet the massive hemorrhage relapsed 2 weeks later. Endoluminal exclusion of external iliac artery using endovascular covered stent-graft at the anastomosis site was performed and the massive bleeding was successfully stopped. The patient was restored to hemodialysis and waited for second kidney transplantation. Candia albicans was detected in the culture of blood and drainage liquid from incision. The other case of hemorrhage occurred at 3 weeks after transplantation. Graft nephrectomy plus endovascular exclusion using covered stent-graft were also performed to stop the massive bleeding. Massive fungal hyphae and spores were observed at the stump of renal graft artery under microscope. The patient received second kidney transplantation after 6 months successfully. No massive hemorrhage caused by fungal infections occurred in micafungin prophylaxis group. CONCLUSIONS: Massive hemorrhage cased by fungal infections after DCD kidney transplantation is usually characterized by delayed and recurrent course, and may result in graft nephrectomy or even death of patients. Endovascular exclusion using covered stent can successfully stop bleeding and rescue life of patients. Two-week preemptive prophylaxis of fungal infections using micafungin can effectively prevent delayed fungal massive hemorrhage in DCD kidney transplantation. PMID- 27266685 TI - [Effect of metanephric mesenchymal stem cells after renal ischemia reperfusion injury in mice]. AB - OBJECTIVE: To study the effect of metanephric mesenchymal stem cells (MMSCs ) after renal ischemia reperfusion injury (IRI). METHODS: C57BL/6J male mice were divided into control group (n=5) and experimental group (n=30). The control group was given a sham operation, while in the experimental group, a model of renal IRI was established. The experimental group was further divided into two groups according to the material injected through the femoral vein: IRI group (injected with normal saline, 10 ml/kg) and cell therapy group (injected with normal saline containing 5*10(5) MMSCs, 10 ml/kg). Samples of blood and kidney tissues were collected from five mice from each group at 12 h, 24 h and 72 h after IRI. The serum creatinine (SCr) level was detected, and the results of kidney tissue pathological staining and Paller score of renal tubules were analyzed to assess the effect of MMSCs after renal IRI. In addition, the expression of microRNA 26a(miR-26a)in kidney tissues was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and compared among the groups. RESULTS: (1) In both IRI group and cell therapy group, the levels of SCr at 12 h, 24 h and 72 h after operation were all significantly higher than those of the control group, besides, the level of SCr at 24 h was significantly higher than that at 12 h and 72 h (all P<0.05). The levels of SCr at 12 h, 24 h and 72 h were of no significant differences between IRI group and cell therapy group(all P>0.05). (2)Paller scores of renal tubules at 12 h, 24 h and 72 h in both IRI group and cell therapy group were significantly higher than those in the control group, and the scores at 24 h were significantly higher than that at 72 h, while the latter were in turn higher than the scores at 12 h (all P<0.05). In the cell therapy group, Paller score of renal tubules at 24 h(57.2+/-6.3)was significantly lower than that in IRI group(70.8+/-14.8) (P<0.05). Histological examination showed renal tubular epithelial cell atrophy, swelling and protein cast in kidney tissues from IRI group at 24 h, compared with the control group and the cell therapy group at the same time.(3) In IRI group and cell therapy group, the levels of miR-26a in the kidney tissues at 12 h and 24 h were significantly lower than those of the control group (P<0.05). In the cell therapy group, the level of miR-26a in the kidney tissues at 24 h (0.416+/-0.139) and 72 h (1.152+/-0.239)were significantly higher than that in the IRI group(0.244+/-0.067, 0.855+/-0.038, both P<0.05). A negative correlation between the levels of miR-26a and SCr level were found (r= 0.5, P<0.05). CONCLUSION: MMSCs have a certain repairing effect on renal IRI, accompanied by an increase in miR-26a expression. PMID- 27266686 TI - [Propensity score matching-based analysis of short-term outcomes of Laparoscopic assisted Natural Orifice Specimen Extraction for left colorectal cancer radical resection]. AB - OBJECTIVE: To explore short-term outcomes obtained with Laparoscopic-assisted Natural Orifice Specimen Extraction for left colorectal cancer radical resection. METHODS: A total of 123 patients with left colorectal tumor who had undergone laparoscopic surgery between Jan.2014 and Jun.2015 were reviewed. According to surgical approach, transanal specimen extraction using the Cai Tube (study group, n=29) and trans-abdominal incision specimen extraction (control group, n=123) were studied. Propensity score matching was applied at a ratio of 1?1 comparing the study (n=23) and control (n=23) groups. RESULTS: The two matched groups had similar baseline characteristics. There was no significant difference in the length of distal or proximal resection margin, the rate of circumferential resection negative margin, the estimated blood loss, the levels of C-reactive protein on 2nd day after surgery, the postoperative time to take liquid, the postoperative hospital day, the hospital fee and the postoperative anal function. The study group presented longer operative time[(237.8+/-68.1)min vs (168.9+/ 47.5)min, P<0.05], less number of lymph nodes dissected (12.4+/-5.4 vs 16.4+/ 7.2, P<0.05), higher white cell count on 2nd day after surgery[(11.7+/ 3.4)*10(9)/L vs (9.4+/-2.6)*10(9)/L, P<0.05], but quicker postoperative recovery of bowel function[(2.6+/-0.7)d vs (3.4+/-0.7)d, P<0.05], shorter postoperative ambulation time[(2.3+/-0.6)d vs (3.6+/-0.7)d, P<0.05], lower rate of postoperative complications (0/23 vs 6/23, P<0.05) and lower rate of utilization of painkillers in addition to postoperative analgesia pump (1/20 vs 9/23, P<0.05). CONCLUSION: Laparoscopic-assisted left colorectal cancer radical resection using the Cai Tube is in line with oncologic principle, less pain, quicker recovery and better cosmetic results. PMID- 27266687 TI - [Survival analysis of gastric cancer cases with pathological complete response received neoadjuvant chemotherapy]. AB - OBJECTIVE: To study the survival situation of gastric cancer patients with pathological complete response (pCR)following neoadjuvant chemotherapy (NAC). METHODS: The clinical data of patients with gastric cancer treated with NAC following by surgical resection between Jan 2011 and Dec 2013 at General Hospital of Chinese People's Liberation Army was analyzed retrospectively. RESULTS: A total of 23 patients (16.0%, 23/144)achieved pathologic complete response. The median follow-up time of the survivors was 42.8 (range 16.0-58.7)months. All patients underwent R0 resection and D2 lymphadenectomy. The overall survival and recurrence-free survival rates at 3 years were 95.7% and 90.3%. CONCLUSIONS: The patients with advanced gastric cancer after neoadjuvant chemotherapy have good prognosis. Modified chemotherapy regimens may further improve the pathological complete response rate. PMID- 27266688 TI - [Clinical research of second resection on early stage primary bladder adenocarcinoma and literature review]. AB - OBJECTIVE: To investigate the clinical and pathological characteristics, as well as the diagnosis and treatment of primary bladder adenocarcinoma in the early stage. METHODS: The clinical features, pathological results, diagnosis and treatment profiles of 7 cases of primary bladder adenocarcinoma admitted in Affiliated Hospital of Nantong University from January 2010 to July 2015 were analyzed ret rospectively. RESULTS: All seven cases were diagnosed pathologically as primary bladder adenocarinoma.Histological staging T1 was revealed in six cases, while T2 in one case after the first resection.After four weeks, all patients received the second resection while one patient underwent immediately radical cystectomy. Multimodality therapy such as radiotherapy or chemotherapy was performed for longer postoperative survival.only one man died while another patient had been healthy for 6 years till January 2016. CONCLUSION: Primary bladder adenocarcinoma is a highly malignant disease in bladder cancer.According to the results of the second resection, multimodality therapy for patients in early stage with no lymph node or other organs metastasis can improve the quality of life without affectiong their lives. PMID- 27266689 TI - [Discussion of laparoscopic transabdominal preperitoneal repair for recurrent inguinal hernia]. AB - OBJECTIVE: To explore the surgical techniques and the clinical efficacy of laparoscopic transabdominal preperitoneal repair (TAPP) for recurrent inguinal hernia. METHODS: Clinical data of 367 patients with recurrent inguinal hernia who underwent TAPP repair from Mar. 2009 to Mar. 2015 in Beijing Chao-Yang Hospital of Capital Medical University were analyzed retrospectively. RESULTS: Laparoscopic operations were completed successfully in 365 cases, however, 2 cases were converted to open surgery.The operation time was (55.7+/-19.3) min (30 100 min) and the hospital stay was (4.9+/-2.7) d (2-12 d). The incidences of postoperative pain, hydrocele, and urinary retention were 4.1%(15/367), 13.1%(48/367), and 1.3%(5/367) respectively.Other complications such as foreign body sensation, wound infection, and intestinal obstruction.All cases were followed up from 3 to 72 months ((36.5+/-14.7) months), 2 recurrent cases was observed and no mesh infection and long-term chronic pain were observed. CONCLUSIONS: Laparoscopic TAPP repair has advantages of minimal invasion and few complications, which is safe and effective for recurrent inguinal hernia. PMID- 27266690 TI - [The effect of Notch1 on myocardial ischemia reperfusion injury]. AB - OBJECTIVE: To investigate the protective effects of Notch1 on myocardial ischemia reperfusion injury and explore underlying molecular mechanism. METHODS: H9c2 cells were exposed to hypoxia/reoxygenation (H/R), ischemic preconditioning (IPC) and ischemic postconditioning (IPost) treatment following infection with lentiviral vector-Notch1 intracellular domain (Lv-N1ICD) or Lv-N1ICD-shRNA, and divided into control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD shRNA group, IPost group, IPost+ N1ICD-shRNA group, respectively. Apoptosis was detected by Annexin V/propidium iodide (PI), and reactive oxygen species (ROS) was detected by 2', 7'dichlorofluorescin-diacetate (DCFH-DA). The expression of p glycogen synthase kinase-3beta (p-GSK-3beta)/GSK-3beta were detected by Western blot analysis. RESULTS: The apoptosis rate of cardiomyocytes in control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD-shRNA group, IPost group, IPost+ N1ICD-shRNA group was (5.34+/-1.70)%, (47.03+/-4.10)%, (33.89+/-12.25)%, (35.85+/-3.17)%, (51.12+/-8.22)%, (37.35+/-3.82)%, (47.90+/-3.08)%, respectively, showing significant differences in all group (F=18.47, P<0.05). ROS in control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD-shRNA group, IPost group, IPost+ N1ICD-shRNA group was 624.66+/-79.52, 1 221.87+/-63.66, 913.12+/ 115.82, 935.85+/-201.62, 1 204.03+/-113.82, 967.15+/-106.11, 1 296.59+/-222.38, respectively, showing significant differences in all group (F=8.77, P<0.05). The ratio of p-GSK-3beta to GSK-3beta in control group, H/R group, H/R+ N1ICD group, IPC group, IPC+ N1ICD-shRNA group, IPost group, IPost+ N1ICD-shRNA group was 0.58+/-0.12, 0.62+/-0.20, 1.24+/-0.09, 1.16+/-0.12, 0.72+/-0.15, 1.16+/-0.12, 0.75+/-0.12, respectively, showing significant differences in all group (F=11.21, P<0.05). CONCLUSION: As an endogenous cardioprotective factor, Notch1 reduces myocardial ischemia reperfusion injury by promoting GSK-3beta phosphorylation, inhibiting cardiomyocyte apoptosis and reducing ROS formation. PMID- 27266691 TI - [Effect of CD40 knock out on cytotoxic effector function in CD8(+) T cell of mice with cigarette smoke-induced emphysema]. AB - OBJECTIVE: To explore the effect of CD40 knock out on the cytotoxic function of CD8(+) T cell of mice with cigarette smoke-induced emphysema. METHODS: A total of 40 male C57 mice were divided into four groups according to the random number table, including CD40(+ /+) control group, CD40(+ /+) smoke-exposure group, CD40( /-)control group, CD40(-/-)smoke-exposure group. The smoke-exposure groups were exposed to cigarette smoke for 24 weeks to establish emphysema model. Morphological changes were evaluated by linear intercepts. The percentages of CD8, perforin, granzyme B positive cells were evaluated by immunohistochemistry. The mRNA expressions of perforin, granzyme B, interleukin (IL) -27 were measured by fluorescent real time quantitative polymerase chain reaction (RT-PCR). The IL 27 cytokine level was tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean linear intercepts in CD40(+ /+) smoke-exposure group was significantly higher than CD40(+ /+) control group, CD40(-/-)control group, and CD40(-/-)smoke-exposure group [(37.2+/-3.6) vs (24.0+/-3.4), (22.5+/-2.4), (29.9+/-1.7) MUm] (all P<0.05). CD40(-/-)smoke-exposure group was higher than CD40(+ /+) control group, CD40(-/-)control group (all P<0.05). The percentages of CD8 positive, perforin positive and granzyme B positive cells in CD40(+ /+) smoke exposure group [(16.3+/-2.3)%, (11.4+/-2.1)%, (10.7+/-1.9)%] were significantly higher than CD40(+ /+) control group [(8.3+/-1.6)%, (5.1+/-1.2)%, (4.6+/-1.0)%], CD40(-/-)control group [ (6.4+/-1.5)%, (4.3+/-1.0)%, (4.2+/-1.0)%] and CD40(-/ )smoke-exposure group [(8.6+/-1.7)%, (5.6+/-1.3)%, (5.5+/-1.3)%] (all P<0.05). RT PCR results showed that the mRNA expressions of perforin, granzyme B and IL-27 in CD40(+ /+) smoke-exposure group [(20.3+/-7.3), (18.3+/-12.3), (2.2+/-0.7)] were significantly higher than CD40(+ /+) control group [(9.4+/-4.8), (10.6+/-3.8), (1.3+/-0.6)], CD40(-/-)control group [ (8.1+/-3.1), (7.7+/-3.5), (1.1+/-0.5)] and CD40(-/-)smoke-exposure group [(12.9+/-6.2), (10.4+/-4.6), (1.5+/-0.4)] (all P<0.05). ELISA results showed that the level of IL-27 in CD40(+ /+) smoke exposure group was significantly higher than CD40(+ /+) control group, CD40(-/ )control group and CD40(-/-)smoke-exposure group [(3 242+/-754) vs (1 627+/-710), (1 600+/-680), (1 850+/-583) ng/L] (all P<0.05). CONCLUSION: Knockout the CD40 gene can inhibit the cytotoxic effector function in CD8(+) T cells of mice with cigarette smoke-induced emphysema, and alleviate the degree of emphysema. PMID- 27266692 TI - [Effect of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury]. AB - OBJECTIVE: To explore the role of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury. METHODS: According to the random digital table, a total number of 32 Wistar rats were divided into 4 groups: sham burn (group A), burn group (group B), 12-week post burn recovery group (group C), and 12-week post burn recovery plus a second burn injury group (group D). In group A and group B, lung tissues were harvested on post burn day 4. After received first burn injury 12 weeks, the group C and group D received separately a second sham burn injury and burn injury. Lung tissues were harvested on post burn day 4 after the second burn injury. All tissues were examined for cells apoptosis by Terminal deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL). Pulmonary fibrosis was assessed by Masson trichrome staining and Sirius red staining. The protein expression levels of cleaved Caspase-3, Bax and Bcl-2 were assessed by Western blot. RESULTS: Both Masson trichrome staining and Sirius red staining showed obvious pulmonary fibrosis in group C and group D. The apoptosis rates of group B, C and D were significantly higher than that in group A ((15.50+/-3.30)%, (7.88+/-3.10)%, (15.88+/-3.23)% vs (2.10+/-1.07)%, all P<0.05). Compared to group A, cleaved Caspase-3 levels were significantly higher in group B, C and D ((0.59+/-0.11), (0.33+/-0.08), (0.73+/-0.13) vs (0.16+/-0.05), all P<0.05). The ratio of Bax/Bcl-2 in group B, C and D also increased significantly ((2.08+/ 0.30), (0.83+/-0.09), (1.54+/-0.12) vs (0.64+/-0.05), all P<0.05). CONCLUSION: Severe burn injury can induce pulmonary fibrosis and mitochondrial apoptosis may play an important role in the development of pulmonary fibrosis. PMID- 27266693 TI - [A meta-analysis of perioperative hyperoxia for the surgical site infections in patients with general surgery]. AB - OBJECTIVE: To systemically analyze the effect of perioperative hyperoxia for the surgical site infections in patients with general surgery. METHODS: Electronic databases consisting of Pubmed, Embase, Cochrane Library, Wanfang Database, CNKI and VIP were systemically searched from established time to November 18, 2015. The randomized controlled trials about perioperative high and low-concentration oxygen for the surgical site infections in patients with general surgery were screened strictly and analyzed by the software of Revman 5.3. The included trials were stratified according to the colorectal or non-colorectal surgery, the duration of oxygen inhalation and the kinds of mixed gas to perform subgroup analyses. Sensitivity analysis was conducted by removing the low-quality trials, etc. The outcome was the surgical site infections. RESULTS: There were 989 relevant articles were searched out. At last, 9 randomized controlled trials consisting of 3 281 patients were included. The 80% oxygen group and 30% oxygen group consists of 1 644 and 1 637 patients, respectively. The rates of surgical site infection were 15.1% (248/1 644) and 17.5% (286/1 637) in the two group. Heterogeneity existed between the included trials and random-effect model was used, the RR=0.80, 95%CI: 0.60-1.08, P=0.15. Therefore, statistically significant difference was not found for the surgical site infections in the general surgery between the perioperative high and low-concentration oxygen. However, the results of subgroup analyses showed that the perioperative hyperoxia decreaced the surgical site infections significant in the subgroups of colorectal surgery and intraoperative plus postoperative 6 h oxygen inhalation. CONCLUSIONS: Perioperative hyperoxia does not reduce surgical site infections in patients with general surgery. However, the results of two subgroup analyses (colorectal surgery and intraoperative plus postoperative 6 h oxygen inhalation trials) show a significantly benefit for perioperative hyperoxia in decreasing surgical site infections. PMID- 27266694 TI - [Evaluation and characterization of the certified reference materials for coagulation factor VIII and IX activity testing]. AB - OBJECTIVE: To evaluate and characterize the certified reference materials for coagulation factor VIII (FVIII) and factor IX (FIX) activity testing. METHODS: The homogeneity and stability of three lots of certified reference materials (F01 F03) with different factor concentrations were evaluated according to guidelines"Reference materials-general and statistical principles for certification","Guidance on evaluating the homogeneity and stability of samples used for proficiency testing"and"Technical Norm of Primary Reference Material". The certified reference materials were characterized by eight laboratories using one-stage method, which were calibrated by the coagulation standard provided by the National Institute for Biological Standards and Control (NIBSC) in UK. RESULTS: The Coefficient of Variation (CV) of homogeneity test of FVIII activity of three lots of certified reference materials were 3.9%, 3.3% and 3.4%, respectively. While that of FIX activity were 3.7%, 3.0% and 1.8%, respectively. The results of one-way ANOVA showed that all certified reference materials had good homogeneity (P>0.05), and the between-bottle homogeneity uncertainties (ubb) of FVIII and FIX activity were 0.5%-2.9% and 0.1%-3.9%, respectively. All certified reference materials stored in -80 C remained stable in 9 months by trend analysis, and the long-term stability uncertainties(ults) of FVIII and FIX activity were 0.5%-5.1% and 1.3%-4.4%, respectively. The characterization uncertainties (uchar) of FVIII and FIX activity testing were 0.9%-2.4% and 1.1% 2.4%, respectively. The combined uncertainties and extended uncertainties (coverage factor k=2) were calculated. The assigned values of each lot of certified reference materials for FVIII activity were (85+/-13)%, (36.0+/-3.4)% and (20.5+/-2.3)%, and that were (102+/-13)%, (47.8+/-6.9)% and (29.3+/-3.8)% for FIX activity, respectively. CONCLUSIONS: The certified reference materials for FVIII and FIX activity testing have good homogeneity and stability. The results of the characterization are accurate and reliable. PMID- 27266695 TI - Organocatalytic Asymmetric Michael Addition of 3-Pyrrolyloxindoles to beta Phthalimidonitroethene for the Synthesis of 3,3'-Disubstituted Oxindoles Bearing Contiguous 3,alpha,beta-Triamino Functionality. AB - An organocatalytic asymmetric Michael addition reaction of 3-pyrrolyloxindoles to beta-phthalimidonitroethene has been developed with a bifunctional thiourea tertiary amine as the catalyst. A range of 3,3'-disubstituted oxindoles bearing contiguous 3,alpha,beta-triamino functionality could be obtained in high yields with good diastereoselectivities and high enantioselectivities (up to 99% yield, 99:1 dr, and 98% ee). The higher reactivity of beta-phthalimidonitroethene compared to the reactivity of ordinary nitroalkenes in the reaction with 3 pyrrolyloxindoles was demonstrated by contrast experiments. PMID- 27266696 TI - Risperidone-induced priapism in an autistic child: a case report. AB - BACKGROUND: Priapism is a prolonged stimulation with painful, persistent penile erection unaccompanied by sexual desire. It is a rare but serious urological emergency. Risperidone is an atypical antipsychotic widely prescribed for the treatment of behavior problems in children with autism spectrum disorder. It seems associated with priapism in children. CASE PRESENTATION: We present a case of a 12-year-old Moroccan boy diagnosed with autism spectrum disorder who developed priapism while on an existing regimen of risperidone, and we report the treatment decisions that followed. CONCLUSIONS: Clinicians who prescribe risperidone should be aware of the possibility of this rare complication in their patients. Information about this possible side effect and instructions regarding appropriate response should be made available to caregivers of those in the at risk group of young patients. PMID- 27266697 TI - The impact of albendazole treatment on the incidence of viral- and bacterial induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial. AB - BACKGROUND: Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. METHODS/DESIGN: This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events. DISCUSSION: In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in co infected populations. In this trial, we will examine how anthelmintic treatment impacts host susceptibility to diarrheal infections, with the aim of informing deworming programs of any indirect effects of mass anthelmintic administrations on co-infecting enteric pathogens. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02597556 . Registered on 3 November 2015. PMID- 27266698 TI - Arterial stiffness in patients with coronary artery disease: relation with in stent restenosis following percutaneous coronary intervention. AB - BACKGROUND: Coronary artery disease (CAD) is one of the most important issues in modern medicine due to its high mortality and prevalence. An early detection and prevention can reduce morbidity and mortality. Arterial stiffness is a potent and independent predictor of CAD. We aimed to investigate the arterial stiffness in CAD patients undergoing the coronary angiography. Also, we investigated a possible correlation between arterial stiffness and in-stent restenosis (ISR), an important limitation of percutaneous coronary intervention (PCI). METHODS: The study included 160 patients undergoing coronary angiography, treated either with PCI or with CABG. The pulse wave velocity (PWV) and augmentation index (AIx) were measured by the Arteriograph. RESULTS: PWV in the CAD group (12.24 +/- 2.78 m/s) was significantly higher compared to the control group (8.27 +/- 1.89 m/s). PWV in ISR and left main (LM) stenosis group (14.03 +/- 3.15 and 13.89 +/- 2.95 m/s) was significantly higher compared to the control and CAD groups. Peripheral and central AIx were significantly higher in CAD group (1.38 +/- 30.63 % and 38.35 +/ 15.52 %) than in control group (-11.35 +/- 26.74 % and 26.91 +/- 10.62 %). Patients with LM stenosis have significantly higher values of peripheral and central AIx (23.37 +/- 23.77 % and 49.71 +/- 12.02 %) than the CAD and ISR group. CONCLUSIONS: The study confirmed a positive correlation between arterial stiffness measures, PWV and AIx, and CAD. Also, this study showed the correlation between PWV and ISR which can help to select more appropriate stent. PMID- 27266699 TI - Integrated miRNA and mRNA expression profiling in fetal hippocampus with Down syndrome. AB - BACKGROUNDS: Down syndrome (DS), caused by triplication of human chromosome 21, is the most common aneuploidies. The main characteristic of DS patients is intellectual disability. MicroRNAs (miRNAs) play important regulatory roles in various biological processes, such as embryonic development, cell differentiation, proliferation and apoptosis. Several miRNAs have shown association with DS. However, the role of miRNAs in DS patients has not been well elaborated. METHODS: In this research, total RNA extracted from fetal hippocampal tissues was used to analyze miRNA and mRNA expression via Affymetrix miRNA 4.0 and PrimeView Human Gene Expression Array, respectively. Then miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their predicted target mRNAs. Microarray data were further validated by real-time PCR. Regulation of zeste homolog 2 (EZH2) expression by hsa-miR-138 was determined by luciferase reporter assay. RESULTS: We analyzed microRNA expression profile in hippocampal tissues from DS fetal using miRNA microarray. Further with the use of mRNA microarray data, we integrate miRNA expression and mRNA expression in hippocampus of trisomy 21 fetus to elucidate the mechanism that underlying DS abnormalities. We characterized the repertoire of specific miRNAs involved in hippocampus in trisomy 21 patients, highlighting hsa-miR-138 and hsa-miR-409, in particular the importance of hsa-miR 138, especially the -5p strand. Furthermore, the expression level of predicted target genes of hsa-miR-138-5p in trisomy 21 fetus, including zeste homolog 2 (EZH2) were further confirmed. In addition, luciferase assay indicated that EZH2 was a direct target of hsa-miR-138 in HEK293T cells. CONCLUSION: The function of hsa-miR-138-5p and its target EZH2 was involved in hippocampus in DS patients. Our findings provide a clue to study the underlying molecular mechanisms in DS patients, and its potential contribution in improving understanding of intellectual disability development in DS patients. PMID- 27266700 TI - Clinical exhibition of increased accommodative loads for binocular fusion in patients with basic intermittent exotropia. AB - BACKGROUND: To investigate the accommodative loads change needed to maintain binocular fusion in patients with intermittent exotropia (IXT). METHODS: Seventeen consecutive patients with basic IXT and 15 normal controls were recruited. The WAM-5500 autorefractor (GrandSeiko, Fukuyama, Japan) was used to measure refractive error (D) under binocular and monocular viewing conditions at 6 m, 50 cm, 33 cm and 20 cm. The difference between binocular and monocular refractive error (D) at each distance defined the change in the accommodative load. The changes in accommodative load were compared between IXT patients and normal controls. We also investigated the change in accommodative loads according to the fixing preference in patients with IXT. RESULTS: In IXT patients, the mean angles of deviation were 20.2 +/- 7.19 and 21.0 +/- 8.02 prism diopters at 6 m and 33 cm, respectively. Under binocular viewing, the changes in accommodative loads of each eye in IXT patients were significantly higher at 50, 33 and 20 cm than those of normal controls (p < 0.05, all). The changes in accommodative loads of fixating and deviating eyes at 6 m were not significantly different between IXT patients and normal controls (p = 0.193, 0.155, respectively). The changes in accommodative loads of the fixating eye at each distance were not significantly different from those of the deviating eye in IXT patients (p > 0.05). CONCLUSION: The changes of accommodative loads at near fixation increased more in IXT patients than they did in normal controls while maintaining binocular fusion. PMID- 27266701 TI - Clinical manifestations and cerebrospinal fluid status in ocular syphilis in HIV Negative patients. AB - BACKGROUND: Syphilis with ocular involvement has reemerged as a critical health problem. The aim of the present study was to explore the clinical manifestations and cerebrospinal fluid (CSF) status in ocular syphilis in human immunodeficiency virus (HIV)-negative patients. METHODS: The clinical records of patients with ocular syphilis presenting to the Shanghai Xuhui Central Hospital in the period from January 2011 to December 2012 were retrospectively reviewed. RESULTS: The median age of 25 HIV-negative patients with ocular syphilis was 53 years, 18 patients (72.0 %) were males and 7 (28.0 %) were females. None of them self identified themselves as men who had sex with men (MSM). The ocular lesions included: uveitis (13 cases), optic neuropathy (6 cases), retinal vasculitis (5 cases), retinal detachment (3 cases), and neuroretinitis (4 cases). Serum toluidine red unheated serum test (TRUST) titer ranged from 1 to 512, with a median of 64. Overall, 18 (72.0 %) of the 25 patients had abnormal CSF results, 15 (60.0 %) CSF samples had elevated white blood cell counts, 13 (52.0 %) had elevated protein levels, and 9 (36.0 %) had reactive CSF Venereal Disease Research Laboratory (VDRL) test, respectively. Mann-Whitney U tests showed higher serum TRUST titer (>32) correlated with the abnormal CSF results. CONCLUSIONS: The demographic characteristics of patients with ocular syphilis in this study were different from previous reports. The study showed a high CSF abnormal rate in HIV-negative patients. The recommendation for CSF examination from all patients with ocular syphilis, including HIV-negative cases, is strongly supported by the present data. PMID- 27266702 TI - Panax ginseng and salvia miltiorrhiza supplementation abolishes eccentric exercise-induced vascular stiffening: a double-blind randomized control trial. AB - BACKGROUND: Muscle damage induced by unaccustomed or eccentric exercise results in delayed onset vascular stiffening. We tested the hypothesis that a 7-day supplementation of panax ginseng and salvia miltiorrhiza prior to an acute eccentric exercise could attenuate arterial stiffening. METHODS: By using a double-blind study placebo-controlled randomized design, subjects were randomly assigned to either the Chinese herb (N = 12) or the placebo group (N = 11) and performed a downhill running (eccentric exercise) trial and a control (seated rest) trial. RESULTS: Muscle soreness increased 1-2 days after exercise similarly in both groups, whereas the herb group demonstrated a faster recovery on active range of motion. Plasma creatine kinase concentration increased significantly at 24 h in both groups but the magnitude of increase was attenuated in the herb group. Arterial stiffness as measured by carotid-femoral pulse wave velocity increased significantly at 24 h in the placebo group but such increase was absent in the herb group. Flow-mediated dilation did not change in either group. Plasma concentrations of CRP and IL-6 increased in the placebo group but no such increases were observed in the herb group. Changes in arterial stiffness induced by eccentric exercise were associated with the corresponding changes in IL-6 (r = 0.46, P < 0.05). CONCLUSIONS: A short-term Chinese herb supplementation of panax ginseng and salvia miltiorrhiza ameliorated the delayed onset vascular stiffening induced by acute downhill running exercise. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02007304. Registered Dec. 5, 2013). PMID- 27266703 TI - Risky and rushed public crack cocaine smoking: the potential for supervised inhalation facilities. AB - BACKGROUND: Despite the multitude of public health and community harms associated with crack cocaine use, little is known about factors associated with smoking crack in public and related risks such as rushed public crack smoking. METHODS: Data were derived from two prospective cohort studies of people who use illicit drugs in Vancouver, Canada between 2010 and 2014. Multivariable generalized estimating equations were used to identify the prevalence and correlates of public crack smoking and rushed public crack smoking. RESULTS: In total, 1085 participants who had smoked crack in the prior six months were eligible for the analysis, of which 379 (34.9 %) reported always or usually smoking crack in public in the previous six months at some point during the study period. Factors positively and independently associated with public crack smoking included public injection drug use (adjusted odds ratio [AOR]: 5.42, 95 % confidence interval [CI]: 3.76-7.82), homelessness (AOR: 3.48, 95 % CI: 2.77-4.36), at least daily crack use (AOR: 2.69, 95 % CI: 2.19-3.31), crack pipe sharing (AOR: 1.98, 95 % CI: 1.60-2.46), drug dealing (AOR: 1.59, 95 % CI: 1.30-1.94), recent incarceration (AOR: 1.47, 95 % CI: 1.09-1.98), noticing police presence when buying or using drugs (AOR: 1.30, 95 % CI: 1.06-1.60), and younger age (AOR: 1.03, 95 % CI: 1.01-1.04). Rushed public crack smoking, which was reported by 216 (28.8 %) of 751 participants who had smoked crack in public at least once during the study period, was positively and independently associated with homelessness (AOR: 2.61, 95 % CI: 1.96-3.49), at least daily crack use (AOR: 1.48, 95 % CI: 1.11-1.98), crack pipe sharing (AOR: 1.44, 95 % CI: 1.10-1.89), drug dealing (AOR: 1.39, 95 % CI: 1.04-1.86), and younger age (AOR: 1.02, 95 % CI: 1.01-1.04). CONCLUSIONS: A high prevalence of public crack smoking and rushed public crack smoking was observed in this setting. These findings point to the need for implementing and evaluating evidence-based public health interventions, such as supervised inhalation facilities, to reduce the risks and harms associated with smoking crack in public. PMID- 27266704 TI - Roles of acid-extruding ion transporters in regulation of breast cancer cell growth in a 3-dimensional microenvironment. AB - BACKGROUND: The 3-dimensional (3D) microenvironment of breast carcinomas is characterized by profoundly altered pH homeostasis, reflecting increased metabolic acid production and a confined extracellular space characterized by poor diffusion, yet the relative contributions of specific pH-regulatory transporters to 3D growth are poorly understood. The aim of this work was to determine how 3D spheroid growth of breast cancer cells impacts the expression and spatial organization of major acid extruding proteins, and how these proteins in turn are required for spheroid growth. METHODS: MCF-7 (Luminal-A) and MDA-MB 231 (Triple-negative) human breast cancer cells were grown as ~700-950 MUm diameter spheroids, which were subjected to Western blotting for relevant transporters (2- and 3D growth), quantitative immunohistochemical analysis, and spheroid growth assays. Individual transporter contributions were assessed (i) pharmacologically, (ii) by stable shRNA- and transient siRNA-mediated knockdown, and (iii) by CRISPR/Cas9 knockout. RESULTS: In MCF-7 spheroids, expression of the lactate-H(+) cotransporter MCT1 (SLC16A1) increased from the spheroid periphery to its core, the Na(+),HCO3 (-) cotransporter NBCn1 (SLC4A7) was most highly expressed at the periphery, and the Na(+)/H(+) exchanger NHE1 (SLC9A1) and MCT4 (SLC16A3) were evenly distributed. A similar pattern was seen in MDA-MB-231 spheroids, except that these cells do not express MCT1. The relative total expression of NBCn1 and NHE1 was decreased in 3D compared to 2D, while that of MCT1 and MCT4 was unaltered. Inhibition of MCT1 (AR-C155858) attenuated MCF-7 spheroid growth and this was exacerbated by addition of S0859, an inhibitor of Na(+),HCO3 (-) cotransporters and MCTs. The pharmacological data was recapitulated by stable knockdown of MCT1 or NBCn1, whereas knockdown of MCT4 had no effect. CRISPR/Cas9 knockout of NHE1, but neither partial NHE1 knockdown nor the NHE1 inhibitor cariporide, inhibited MCF-7 spheroid growth. In contrast, growth of MDA-MB-231 spheroids was inhibited by stable or transient NHE1 knockdown and by NHE1 knockout, but not by knockdown of NBCn1 or MCT4. CONCLUSIONS: This work demonstrates the distinct expression and localization patterns of four major acid-extruding transporters in 3D spheroids of human breast cancer cells and reveals that 3D growth is dependent on these transporters in a cell type-dependent manner, with potentially important implications for breast cancer therapy. PMID- 27266707 TI - Snatching defeat from the jaws of Pyrrhic victory. PMID- 27266706 TI - Combined [(18)F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice. AB - BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability. Neuroinflammation contributes to acute damage after TBI and modulates long-term evolution of degenerative and regenerative responses to injury. The aim of the present study was to evaluate the relationship of microglia activation to trauma severity, brain energy metabolism, and cellular reactions to injury in a mouse closed head injury model using combined in vivo PET imaging, ex vivo autoradiography, and immunohistochemistry. METHODS: A weight-drop closed head injury model was used to produce a mixed diffuse and focal TBI or a purely diffuse mild TBI (mTBI) in C57BL6 mice. Lesion severity was determined by evaluating histological damage and functional outcome using a standardized neuroscore (NSS), gliosis, and axonal injury by immunohistochemistry. Repeated intra-individual in vivo MUPET imaging with the specific 18-kDa translocator protein (TSPO) radioligand [(18)F]DPA-714 was performed on day 1, 7, and 16 and [(18)F]FDG-MUPET imaging for energy metabolism on days 2-5 after trauma using freshly synthesized radiotracers. Immediately after [(18)F]DPA-714-MUPET imaging on days 7 and 16, cellular identity of the [(18)F]DPA-714 uptake was confirmed by exposing freshly cut cryosections to film autoradiography and successive immunostaining with antibodies against the microglia/macrophage marker IBA-1. RESULTS: Functional outcome correlated with focal brain lesions, gliosis, and axonal injury. [(18)F]DPA-714-MUPET showed increased radiotracer uptake in focal brain lesions on days 7 and 16 after TBI and correlated with reduced cerebral [(18)F]FDG uptake on days 2-5, with functional outcome and number of IBA-1 positive cells on day 7. In autoradiography, [(18)F]DPA-714 uptake co-localized with areas of IBA1-positive staining and correlated strongly with both NSS and the number of IBA1-positive cells, gliosis, and axonal injury. After mTBI, numbers of IBA-1 positive cells with microglial morphology increased in both brain hemispheres; however, uptake of [(18)F]DPA-714 was not increased in autoradiography or in MUPET imaging. CONCLUSIONS: [(18)F]DPA-714 uptake in MUPET/autoradiography correlates with trauma severity, brain metabolic deficits, and microglia activation after closed head TBI. PMID- 27266705 TI - Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia. AB - BACKGROUND: Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci. RESULTS: We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta = 3.7 * 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 * 10(-7) and DQB1*06:02 P = 6.1 * 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 * 10( 16)). CONCLUSIONS: We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP. PMID- 27266709 TI - Corrigendum. PMID- 27266710 TI - Correction to Conferring Natural-Derived Porous Microspheres with Surface Multifunctionality through Facile Coordination-Enabled Self-Assembly Process. PMID- 27266708 TI - Higher-order assemblies of oligomeric cargo receptor complexes form the membrane scaffold of the Cvt vesicle. AB - Selective autophagy is the mechanism by which large cargos are specifically sequestered for degradation. The structural details of cargo and receptor assembly giving rise to autophagic vesicles remain to be elucidated. We utilize the yeast cytoplasm-to-vacuole targeting (Cvt) pathway, a prototype of selective autophagy, together with a multi-scale analysis approach to study the molecular structure of Cvt vesicles. We report the oligomeric nature of the major Cvt cargo Ape1 with a combined 2.8 A X-ray and negative stain EM structure, as well as the secondary cargo Ams1 with a 6.3 A cryo-EM structure. We show that the major dodecameric cargo prApe1 exhibits a tendency to form higher-order chain structures that are broken upon interaction with the receptor Atg19 in vitro The stoichiometry of these cargo-receptor complexes is key to maintaining the size of the Cvt aggregate in vivo Using correlative light and electron microscopy, we further visualize key stages of Cvt vesicle biogenesis. Our findings suggest that Atg19 interaction limits Ape1 aggregate size while serving as a vehicle for vacuolar delivery of tetrameric Ams1. PMID- 27266711 TI - Mediastinal myelolipoma showing gradual enlargement over 9 years: a case report. AB - BACKGROUND: Myelolipoma is a rare benign tumor composed of mature adipose tissue and normal hematopoietic tissue. Although surgical resection has been recommended due to the potential of progressive enlargement, the natural history of mediastinal myelolipoma has not yet been described. Herein we report a surgically resected mediastinal myelolipoma showing gradual enlargement over a period of 9 years. CASE PRESENTATION: A 70-year-old woman presented with a posterior mediastinal mass shadow detected by computed tomography (CT) examination. She had a medical history of sigmoidectomy for colon cancer 13 years previously. A CT scan showed a smooth, well-demarcated 2.8 * 2.1-cm paravertebral mass shadow, composed of a fat density area and a soft tissue density area, which showed gradual enlargement from a 1.6 * 1.0-cm nodule 9 years previously. This was not accompanied by chronic anemia or hematologic disease including thalassemia, and no abnormal accumulation was observed on bone marrow scintigraphy or fluoro-2 deoxyglucose positron emission tomography. With a clinical diagnosis of mediastinal myelolipoma, surgical resection was performed, and pathological examination confirmed the diagnosis. CONCLUSIONS: We experienced a rare case with mediastinal myelolipoma showing gradual enlargement, with a tumor doubling time of 1,212 days. PMID- 27266713 TI - Nutritional Epigenetics and the Prevention of Hepatocellular Carcinoma with Bioactive Food Constituents. AB - Hepatocellular carcinoma (HCC) is an aggressive and life-threatening disease often diagnosed at intermediate or advanced stages, which substantially limits therapeutic approaches to its successful treatment. This indicates that the prevention of HCC may be the most promising strategy in reducing its incidence and mortality. Emerging evidence indicates that numerous nutrients and nonnutrient dietary bioactive components can reduce the occurrence and/or delay the development of HCC through modifications of deregulated epigenetic mechanisms. This review examines the existing knowledge on the epigenetic mechanism-based studies in in vitro and in vivo models of HCC on the chemopreventive potential of epigenetic food components, including dietary methyl group donors, epigallocatechin-3-gallate, sodium butyrate, resveratrol, curcumin, and sulforaphane, on liver carcinogenesis. Future direction and potential challenges in the effective use of bioactive food constituents in the prevention of HCC are highlighted and discussed. PMID- 27266712 TI - Translational research in diagnosis and management of soft tissue tumours. AB - Finding a soft tissue mass in the superficial regions is a common event in daily clinical practice. Correct management of the diagnostic process is crucial to avoid blunders. Diagnosis is posed by pathology, although both imaging and a better understanding of the cellular and molecular mechanisms play an important a role in the characterization, staging and follow-up of soft tissue masses. Cellular and molecular mechanisms can explain either the development of chemo resistance and the underlying pre- and post-surgery metastasis formation. These are mandatory to improve prognosis and unveil novel parameters predicting therapeutic response. Imaging mainly involves ultrasound and MR and is fundamental not only in diagnosis but also in the first step of therapy: the biopsy. Novel imaging techniques like Ultrasound Elastosonography, Dynamic Contrast-Enhanced MR imaging (DCE), Diffusion Weighted MR imaging (DWI) and MR Spectroscopy (MRS) are discussed. This paper aims at reviewing and discussing pathological methods and imaging in the diagnosis of soft tissue masses underscoring that the most appropriate treatment depends on advanced molecular and radiological studies. PMID- 27266714 TI - UPLC-QTOFMS(E)-Guided Dereplication of the Endangered Chinese Species Garcinia paucinervis to Identify Additional Benzophenone Derivatives. AB - A number of Garcinia species accumulate benzophenone derivatives that may be useful for the treatment of breast cancer. The dereplication of new benzophenone derivatives from Garcinia species is challenging due to the occurrence of multiple isomers and the known compounds found in their extracts. In the current study, a strategy is described using the UPLC-QTOFMS(E) technique to identify tentatively the known and uncharacterized benzophenones of interest based upon the characteristic fragmentation ions. Several UPLC-QTOFMS peaks (a-ee) appeared to contain benzophenone derivatives, and 12 of these peaks contained compounds with MS ionization profiles not consistent with previously identified compounds from the seeds of Garcinia paucinervis, an endangered Chinese species. The targeted isolation of unidentified compounds of interest afforded five new benzophenones, paucinones E-I (1-5), which were determined by MS and NMR analysis and ECD spectroscopy. These compounds were evaluated for cytotoxicity against three breast cancer cell lines inclusive of MDA-MB-231, SKBR3, and MCF-7. These results indicate that the UPLC-QTOFMS(E)-guided isolation procedure is an efficient strategy for isolating new benzophenones from Garcinia species. PMID- 27266715 TI - RNA structure through multidimensional chemical mapping. AB - The discoveries of myriad non-coding RNA molecules, each transiting through multiple flexible states in cells or virions, present major challenges for structure determination. Advances in high-throughput chemical mapping give new routes for characterizing entire transcriptomes in vivo, but the resulting one dimensional data generally remain too information-poor to allow accurate de novo structure determination. Multidimensional chemical mapping (MCM) methods seek to address this challenge. Mutate-and-map (M2), RNA interaction groups by mutational profiling (RING-MaP and MaP-2D analysis) and multiplexed *OH cleavage analysis (MOHCA) measure how the chemical reactivities of every nucleotide in an RNA molecule change in response to modifications at every other nucleotide. A growing body of in vitro blind tests and compensatory mutation/rescue experiments indicate that MCM methods give consistently accurate secondary structures and global tertiary structures for ribozymes, ribosomal domains and ligand-bound riboswitch aptamers up to 200 nucleotides in length. Importantly, MCM analyses provide detailed information on structurally heterogeneous RNA states, such as ligand-free riboswitches that are functionally important but difficult to resolve with other approaches. The sequencing requirements of currently available MCM protocols scale at least quadratically with RNA length, precluding general application to transcriptomes or viral genomes at present. We propose a modify cross-link-map (MXM) expansion to overcome this and other current limitations to resolving the in vivo 'RNA structurome'. PMID- 27266716 TI - Localization and Possible Function of P2X Receptors in Normal and Diseased Retinae. AB - Purines, when present in the extracellular space, can mediate fast neurotransmission in the retina and central nervous system. Over the last decade there has been emerging evidence for the expression of P2X and P2Y receptors in a range of retinal neuronal subtypes. These results have highlighted important roles for purines in modulating specific retinal circuits, including the rod pathway and amacrine cell circuits. Traditionally, synaptic release of adenosine triphosphate (ATP) involves the novel anion vesicular nucleotide transporter, VNUT, which has recently been identified in a single wide-field amacrine cell population. In addition, nontraditional, conductive mechanisms of release have also been described in the retina. In the synapse, the enzymes involved in rapid degradation of purines are present in both plexiform layers of the retina. A role for P2X receptors in retinal diseases has also emerged recently. High concentrations of ATP lead to photoreceptor loss, through mechanisms involving P2X7 receptors. In addition, activation of P2X7 receptors is associated with activation of the inflammasome, a protein complex important for the release of proinflammatory cytokines. P2X receptors, especially P2X7, are emerging as targets to combat retinal disease. PMID- 27266717 TI - Facile Self-Cross-Linking Synthesis of 3D Nanoporous Co3O4/Carbon Hybrid Electrode Materials for Supercapacitors. AB - A hybrid electrode material with ultrafine Co3O4 nanoparticles embedded throughout a hierarchically nanoporous graphitic carbon matrix has been obtained via a facile self-cross-linking route. Sodium alginate, a biopolymer with an ability of cross-linking with multivalent cobalt cations to form ordered microcrystalline zones, is used as a carbon source to produce nanoporous carbon frameworks of the hybrids. Ultrafine Co3O4 nanoparticles with tunable particle size (3-30 nm) are in situ grown within the nanoporous graphitic carbon frameworks by a simple carbonization of Co-cross-linked alginate. The obtained hybrid electrodes exhibit high specific capacitance of 645, 548, 486, and 347 F/g at scan rates of 5, 10, 20, and 50 mV/s, respectively, and excellent cycle performance with only 1% fading in capacitance after 10 000 cycles at a high current density of 20 A/g. Such excellent capacitive performance is ascribed to the collaborative contributions of well-dispersed ultrafine Co3O4 nanoparticles and conductive nanoporous carbon frameworks. PMID- 27266718 TI - Efficiency of methylated DNA immunoprecipitation bisulphite sequencing for whole genome DNA methylation analysis. AB - AIMS: We compared four common methods for measuring DNA methylation levels and recommended the most efficient method in terms of cost and coverage. MATERIALS & METHODS: The DNA methylation status of liver and stomach tissues was profiled using four different methods, whole-genome bisulphite sequencing (WG-BS), targeted bisulphite sequencing (Targeted-BS), methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA immunoprecipitation bisulphite sequencing (MeDIP-BS). We calculated DNA methylation levels using each method and compared the results. RESULTS: MeDIP-BS yielded the most similar DNA methylation profile to WG-BS, with 20 times less data, suggesting remarkable cost savings and coverage efficiency compared with the other methods. CONCLUSION: MeDIP-BS is a practical cost-effective method for analyzing whole-genome DNA methylation that is highly accurate at base-pair resolution. PMID- 27266719 TI - Mothering and anxiety: Social support and competence as mitigating factors for first-time mothers. AB - This study investigated anxiety as a phenomenon distinct from depression and evaluated several variables that influence anxiety in first-time mothers. This explored the relationship between maternal sense of competence (both of mothering and efficacy) and perceived social support (from family, friends, and significant others) and first-time mothers' postpartum anxiety, when depression, socioeconomic status (SES), and marital status were controlled for. The population studied were 86 first-time mothers made up of women with children 24 months or younger in two populations of Kentucky and Michigan. The constructs of maternal sense of competence and perceived social support were found to be significant in explaining first-time mothers' anxiety. The study concluded that a combined association of perceived social support and maternal sense of competence were associated with a 34% (change in R-squared = .339) decrease of a first-time mothers' anxiety. However, not all types of social support, or maternal competence appeared to be equally important with regards to maternal anxiety: social support from friends and family and maternal sense of competence in regard to productivity appeared to be most significant. Lastly, some recommendations for health practitioners who work with mothers are provided. PMID- 27266720 TI - Ceruloplasmin decreases respiratory burst reaction during pregnancy. AB - Testing of pregnant women reveals weakening of neutrophil-mediated effector functions, such as reactive oxygen species generation. This study provides data confirming the phenomenon, gained through application of the flow cytometry technique. Key factors influencing neutrophil functional activity in blood plasma of pregnant women have not been detected so far. At the same time, concentration of ceruloplasmin - a copper-containing glycoprotein - is known to increase in blood significantly during pregnancy. We observed the negative correlation between ceruloplasmin concentration in blood plasma of pregnant women and the intensity of respiratory burst of neutrophils. Fractionation of plasma using gel filtration revealed that ceruloplasmin-containing fraction demonstrated suppression of the respiratory burst reaction. Partial elimination of ceruloplasmin from the blood of pregnant women, performed with the help of specific antibodies and followed by immunoprecipitation, leads to an increased respiratory burst reaction. On the contrary, addition of ceruloplasmin to blood samples of healthy donors noticeably decreases the respiratory burst reaction. The results presented prove that change in ceruloplasmin level in plasma is necessary and sufficient for modulating the ability of neutrophils to produce reactive oxygen species during pregnancy. PMID- 27266721 TI - Pharmacogenetic-based strategy using de novo tacrolimus once daily after kidney transplantation: prospective pilot study. AB - AIM: The once daily tacrolimus formulation (Tac-OD) has been associated with better patient adherence and low variability in exposure. Patients carrying the CYP3A5*1 allele show accelerated clearance of Tac. Authors prospectively evaluate a simplified strategy for Tac-OD administration. PATIENTS & METHODS: After grafting, 151 patients were divided into four groups and received a daily dose calculated according to CYP3A5 genotypes and unchanged for the first 3 days: CYP3A5*3/*3: 0.20 mg/kg/day, CYP3A5*3/*3: 0.25 mg/kg/day, CYP3A5*1/*3: 0.30 mg/kg/day and CYP3A5*1/*1: 0.35 mg/kg/day. The dose was adaptated on day 4 and remained unchanged a further three days and so on. RESULTS: On day 3, median Cmin fell within the therapeutic range in all study groups. CYP3A5 expressors require significantly higher Tac-OD throughout the follow-up period to achieve a comparable Cmin. CONCLUSION: This simplified strategy does not hamper treatment efficacy. PMID- 27266722 TI - T1a Versus T1b Differentiated Thyroid Cancers: Do We Need to Make the Distinction? AB - BACKGROUND: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system trialed a subdivision of T1 tumors into T1a (<1 cm) and T1b (1.0-2 cm). The 2009 American Thyroid Association (ATA) guidelines recommended total thyroidectomy for tumors >1 cm, and lobectomy for those <=1 cm. These AJCC staging parameters remain a focus of debate, and ATA guidelines are in transition. The aim of this study was to determine if the T1 staging subdivision is associated with different treatment strategies and patterns of patient survival. METHODS: All adult patients with AJCC pT1 differentiated thyroid cancer (DTC) from the National Cancer Data Base (NCDB; 1998-2012) and Surveillance, Epidemiology, and End Results (SEER) program (2004-2012) were divided into two groups based on tumor size: T1a versus T1b. Demographic, clinical, and pathologic features were evaluated. Multivariate regression analysis was used to determine factors associated with undergoing total thyroidectomy and radioactive iodine. Cox proportional hazards models were performed to determine factors associated with overall and disease-specific survival. RESULTS: Among 149,912 DTC patients, 98,111 (65.4%) were T1a and 51,801 (34.6%) T1b in the NCDB; in SEER, among 18,381 patients, 11,208 (61.0%) had T1a and 7173 (39.0%) T1b tumors. Patients with T1b cancers were younger (48 vs. 51 years T1a) and more likely to have private insurance (76.2% vs. 74.1%), no comorbidities (86.0% vs. 83.8%), and undergo treatment at academic medical centers (41.4% vs. 40.3%; all p < 0.01). They also were more likely to undergo total thyroidectomy (87.7% vs. 74.3%), and had more lymphovascular invasion (10.2% vs. 3.3%), positive surgical margins (7.9% vs. 3.8%), metastatic lymph nodes (35.8% vs. 23.8%), and distant metastases (0.4% vs. 0.3%; all p < 0.01). Factors associated with radioactive-iodine use included younger patient age, lower income, having insurance, positive surgical margins, and T1b stage (p < 0.01). After adjustment, overall (p = 0.23) and disease specific survival (p = 0.93) were similar among patients with T1a versus T1b tumors. CONCLUSION: These results illustrate that patients with pT1a versus pT1b tumors undergo different treatment strategies. Based on the newly published 2015 ATA guidelines, whereby either lobectomy or total thyroidectomy can be performed for low-risk tumors, it might be anticipated that treatment differences will diminish over time. Therefore, division of AJCC T1 staging into T1a versus T1b subgroups might become obsolete over time. PMID- 27266723 TI - Irreversible Electroporation in the Epidural Space of the Porcine Spine: Effects on Adjacent Structures. AB - Purpose To determine the effects of irreversible electroporation (IRE) on the neural tissues after ablation in the epidural space of the porcine spine. Materials and Methods The institutional animal care and use committee approved this study. With the IRE electrode positioned in the right lateral recess of the spinal epidural space, 20 IRE ablations were performed with computed tomographic (CT) guidance by using different applied voltages in four animals that were euthanized immediately after magnetic resonance (MR) imaging of the spine, performed 6 hours after IRE (terminal group). Histopathologic characteristics of the neural tissues were assessed and used to select a voltage for a survival study. Sixteen CT-guided IRE ablations in the epidural space were performed by using 667 V in four animals that were survived for 7 days (survival group). Clinical characteristics, MR imaging findings (obtained 6 hours after IRE and before euthanasia), histopathologic characteristics, and simulated electric field strengths were assessed. A one-way analysis of variance was used to compare the simulated electric field strength to histologic findings. Results The mean distance between the IRE electrode and the spinal cord and nerve root was 1.71 mm +/- 0.90 and 8.47 mm + 3.44, respectively. There was no clinical evidence of paraplegia after IRE ablation. MR imaging and histopathologic examination showed no neural tissue lesions within the spinal cord; however, five of 16 nerve roots (31.2%) demonstrated moderate wallerian degeneration in the survival group. The severity of histopathologic injury in the survival group was not significantly related to either the simulated electric field strength or the distance between the IRE electrode and the neural structure (P > .05). Conclusion Although the spinal cord appears resistant to the toxic effects of IRE, injury to the nerve roots may be a limiting factor for the use of IRE ablation in the epidural space. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27266724 TI - Effect of Cr(VI) concentration on gas and particle production during iron oxidation in aqueous solutions containing Cl- ions. AB - Zero-valent iron (ZVI) is commonly used as a medium in permeable reactive barriers (PRBs) because of its high reducing ability. The generation of H2 gas in PRBs, however, can decrease the permeability of PRBs and reduce the contact area between the PRB and contaminated groundwater. This study investigated the effect of the initial Cr(VI) concentration ([Cr(VI)init]) in aqueous solutions containing Cl- ions on the generation of H2 gas. ZVI chips were reacted in reactors with 0.5-M NaCl solutions with [Cr(VI)init] ranging between 51 and 303 mg/L. The initial pH was set at 3. The oxidation of ZVI chips by Cr(VI) in aqueous solutions containing Cl- ions produced H2 gas and particles (Fe(III) Cr(III)(oxy)hydroxides). The Cr(VI) removal from aqueous solutions increased as the [Cr(VI)init] increased, as did H2 gas generation. The positive effect of [Cr(VI)init] on H2 gas generation might be due to an increase in the redox potential gradient as [Cr(VI)init] increases. This increased gradient would enhance H+ ion penetration through the passive film (Fe(III) Cr(III)(oxy)hydroxides), which formed on the ZVI surface, by diffusion from the solution to pits beneath the passive film. PMID- 27266725 TI - Phenolic acids, antioxidant and antiproliferative activities of Naviglio(r) extracts from Schizogyne sericea (Asteraceae). AB - Schizogyne sericea, well-known as 'salado', is a halophytic shrub widespread on coastal rocks of Tenerife (Canary Islands). This plant is used traditionally as analgesic, astringent, anti-inflammatory and vulnerary agent. In the present work, we have analysed the aqueous and ethanolic extracts of S. sericea for the content of phenolic acids by HPLC-DAD. The dynamic solid-liquid Naviglio(r) extractor was used to extract the flowering aerial parts. Aqueous extracts showed higher levels of phenolics than ethanolic extracts. S. sericea extracts were rich in chlorogenic and isochlorogenic acids. The Naviglio(r) extracts obtained were assayed for in vitro biological activities, namely antioxidant, antimicrobial and cytotoxicity on tumour cells by DPPH, ABTS, FRAP, agar disc-diffusion and MTT methods, respectively. Results showed that aqueous extracts, being richer in phenolic acids, are endowed with relevant radical scavenging activity (TEAC values in the range 208-960 MUmol TE/g) while ethanolic extracts exhibited noteworthy antiproliferative effects on tumour cells. PMID- 27266726 TI - Estimation and mapping of uranium content of geological units in France. AB - In France, natural radiation accounts for most of the population exposure to ionizing radiation. The Institute for Radiological Protection and Nuclear Safety (IRSN) carries out studies to evaluate the variability of natural radioactivity over the French territory. In this framework, the present study consisted in the evaluation of uranium concentrations in bedrocks. The objective was to provide estimate of uranium content of each geological unit defined in the geological map of France (1:1,000,000). The methodology was based on the interpretation of existing geochemical data (results of whole rock sample analysis) and the knowledge of petrology and lithology of the geological units, which allowed obtaining a first estimate of the uranium content of rocks. Then, this first estimate was improved thanks to some additional information. For example, some particular or regional sedimentary rocks which could present uranium contents higher than those generally observed for these lithologies, were identified. Moreover, databases on mining provided information on the location of uranium and coal/lignite mines and thus indicated the location of particular uranium-rich rocks. The geological units, defined from their boundaries extracted from the geological map of France (1:1,000,000), were finally classified into 5 categories based on their mean uranium content. The map obtained provided useful data for establishing the geogenic radon map of France, but also for mapping countrywide exposure to terrestrial radiation and for the evaluation of background levels of natural radioactivity used for impact assessment of anthropogenic activities. PMID- 27266728 TI - Description and prevalence of Mycoplasma ciconiae sp. nov. isolated from white stork nestlings (Ciconia ciconia). AB - The mycoplasma strain ST 57T was isolated from the trachea of a clinically healthy, free-ranging white stork nestling in Nielitz, Mecklenburg-Western Pomerania, Germany. Strain ST 57T grew in fried-egg-shaped colonies on mycoplasma (SP4) agar plates and was dependent on sterol for growth. The organism fermented glucose and did not hydrolyse arginine or urea. The optimal growth temperature was 37 degrees C, with a temperature range from 23 to 44 degrees C. Strain ST 57Tcould not be identified as a representative of any of the currently described mycoplasma species by alignment of the 16S rRNA gene sequence or 16S-23S intergenic transcribed spacer region, or by immunobinding assays. Thus, this organism appears to be a representative of a novel species, for which the name Mycoplasma ciconiae sp. nov. is proposed. The type strain is ST 57T (=ATCC BAA 2401T=DSM 25251T). Four further strains of this species are included in this description (ST 24=DSM 29908, ST 56 Clone 1=DSM 29054, ST 99=DSM 29909, ST 102=DSM 29010). The prevalence of this mycoplasma species in clinically healthy, white stork nestlings in northern Germany was determined. Our species-specific PCR detected 57.8 % (48/83) of the samples positive for M. ciconiae sp. nov. As this species appears to be widespread in the healthy free-ranging white stork population, we conclude that this species is either apathogenic or an opportunistic pathogen in white storks. PMID- 27266729 TI - The postcode lottery lives on. AB - The postcode lottery was something that the National Institute for Health and Care Excellence, as it is now called, was originally set up to eradicate back in 1999. PMID- 27266727 TI - Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways? AB - The antimicrobial beta-defensin-like role of hepcidin (HEPC) has been increasingly investigated for its potential role in acute kidney injury (AKI). In sepsis-induced AKI, there is a complex interplay between positive and negative regulation of HEPC, with consequently altered distributions of iron caused by changes in HEPC levels. The aim of the current research was to assess serum HEPC levels in a cohort of septic patients with AKI and investigate the regulatory impact of hypoxia-inducing factor (HIF)-1alpha, erythropoietin (EPO) and inflammation on HEPC levels and related signal cascades in these patients. Baseline, higher levels of SCr (2.3-fold), blood urea nitrogen (BUN) (1.8-fold), uric acid (2.3-fold) and white blood cell (2.3-fold) were noted in septic AKI patients, along with decreased levels of albumin (15.7%), creatinine (44.7%) and BUN/creatinine ratios (23.8%), compared to in normal subjects. These hosts also had increased serum levels of TNFalpha (4.4-times) and TGFbeta1 (3.2-times) compared to controls (p < 0.05). Further, HEPC and HIF-1alpha levels were also increased (8.8- and 3.6-times control levels), while EPO levels were decreased (77.8%) from control levels. After 12 weeks of antibiotic therapy, all septic AKI patients showed significant improvement of the altered markers of kidney dysfunction. In line with significant reductions in serum TNFalpha and TGFbeta1 (25.5% and 26.2%, respectively), HEPC and HIF-1alpha levels were significantly decreased (31.6% and 19.3%), and EPO levels increased (1.9-fold) compared to pretreatment values. There was a significant positive correlation between HEPC levels and kidney function markers (SCr and BUN), inflammatory TNFalpha and TGFbeta1 and serum HIF-1alpha and pAKT in septic AKI patients before and after treatment. Based on the results here, we conclude that HEPC, EPO and HIF-1alpha are involved in the pathogenesis of sepsis-induced AKI and confirm the dominating effects of inflammatory determinants over hypoxia-related complications. PMID- 27266730 TI - Charities call for staff and funds to reduce infant death levels. AB - 'SERIOUS' STAFFING and funding shortages must be addressed urgently if the numbers of stillbirths and neonatal deaths in the UK are to be reduced, charities have urged. PMID- 27266731 TI - Neonatal unit receives prestigious accreditation. AB - A NEONATAL intensive care unit in Southampton has become the first in the country to gain a family-friendly accreditation award from the charity Bliss. PMID- 27266732 TI - New website offers wider content for readers on the go. AB - NURSING CHILDREN and Young People is launching a new website designed to give our readers a better experience when using the journal online. PMID- 27266733 TI - Gaps in community workforce putting pressure on parents. AB - THE WELLCHILD charity has called for workforce and training to be reviewed as it celebrates its tenth anniversary. PMID- 27266734 TI - Wear it with pride. AB - NURSES AT one NHS hospital trust are to be awarded badges for their achievements. PMID- 27266736 TI - Cuts endanger more services. AB - WHEN BARNSLEY council put out its tender for the 0-19 service last autumn, it laid down strict criteria. A ceiling of L4.8 million a year was put on any bids for the service, which incorporates school nursing teams and health visitors. That represented a cut of more than L1 million on the existing contract. PMID- 27266737 TI - Lessons in speed from Formula One. AB - A COLLABORATION between Formula One team Williams and the University Hospital of Wales (UHW) has provided clinicians with a host of ideas about how to improve care. PMID- 27266738 TI - Noticeboard. AB - Courses, events, grants, and awards to progress your career. PMID- 27266742 TI - Research essentials. AB - CONDUCTING RESEARCH to a high standard requires funding and grant applications to funding bodies need a detailed breakdown of justified costs to show value for money. All expenditure must be accounted for, even down to the cost of tea and coffee. PMID- 27266743 TI - Development of more focused questionnaires improves results. AB - The need to elicit parental experiences and perspectives on a child's end of life care is a fundamental element of measuring quality of care but, additionally, is crucial for care improvement and development. PMID- 27266744 TI - Research and commentary. AB - Background Families' experiences at the end of life are affected by the quality of care family and child receive. Parental voices are an important element of gathering information on caring experiences and quality issues. PMID- 27266748 TI - Student voice - Care begins at home. AB - WHILE I don't imagine anyone in any line of work feels happy about calling in sick, I have never known anyone experience the same level of guilt about it as nurses. PMID- 27266749 TI - Storyboarding as an aid to learning about death in children's nursing. AB - The sudden or anticipated death of a child is one of the most challenging and unique experiences that children's nursing students will encounter in practice. There is evidence to suggest that the effect this can have on a practitioner can affect quality of care. Although education for nurses about dealing with death has been studied, there is limited research into the education of those working with dying children and how effective it is in preparing them to deal with the situation. This deficit presents those involved in children's nurse education with a significant challenge and an opportunity to be innovative. This article examines the use of storyboarding as a creative teaching tool to enable children's nursing students to reflect on their experiences of working with children and families in death situations. The wider implications for the use of this technique in practice and education are considered. PMID- 27266750 TI - An experience-based treatment model for children unwilling to eat. AB - Background Guidance during Meals is a two-week inpatient intervention undertaken at the Folke Bernadotte Regional Habilitation Centre, Sweden, to help parents deal with children's eating problems. Parents are given advice about medical and/or behavioural reasons for food selectivity and possible treatment strategies. Aims To identify the way parents handle mealtimes and associated difficulties and investigate parents' opinion on children's progress using Guidance during Meals. Method A questionnaire, consisting of 30 statements and answered by 41 parents, was used to investigate parents' opinions regarding the success of the intervention in altering their child's eating habits at home. Findings Most parents thought that the intervention had helped them and their child, by teaching them how to guide their child during mealtimes, what made it easier for their child to eat, and how to communicate with their child in an encouraging way. Most children retained their increased interest in eating once back at home. These results were not dependent on time of onset of eating problems, number of intervention periods, length of time since the intervention, or gastrostomy. Conclusion The Guidance during Meals intervention helps parents develop knowledge about factors that hinder or facilitate eating in their child and tools that can help their child finish meals, and gives them a sense of hope that positive change can occur. PMID- 27266751 TI - Children's nurses' post-operative pain assessment practices. AB - Pain assessment is crucial to achieving optimal pain management in children. Pain that is insufficiently controlled can have extensive short- and long-term repercussions. Many studies continue to report that children experience unnecessary post-operative pain when they are in hospital. The purpose of this literature review was to explore post-operative pain assessment practices used by children's nurses. A literature search of databases was undertaken and inclusion criteria identified. Four themes emerged: pain assessment tools; behavioural cues; documentation; and communication between child, parent/carer and nurse. The findings showed that pain assessment tools were inadequately used, that children's behavioural cues were misinterpreted, and that there was inconsistency in the documentation of pain scores and in communication about pain scores between children, parent/carer and nurse. Addressing the key issues identified from the articles reviewed can help improve nursing practice and care. PMID- 27266752 TI - How a short stay unit can reduce children's waiting times. AB - Admitting children to emergency departments (EDs) often places them in an environment better suited to the treatment of adult patients. These children are often triaged and treated as adults, resulting in children being given the wrong triage categories and having their treatment delayed. EDs have problems giving drugs to children, staff are unfamiliar with children's emergency care, and children find EDs frightening. A paediatric emergency short stay unit (PESSU) was opened at Caboolture Hospital, Queensland, Australia, in January 2014. Admission to the PESSU has significantly reduced waiting times for children arriving at the ED and enabled specialist nursing and medical care to be provided quickly. This has been supported by the development of the paediatric flow nurse role ( Gray et al 2016 ). PMID- 27266753 TI - The clinical and economic burden of significant bleeding during lung resection surgery: A retrospective matched cohort analysis of real-world data. AB - OBJECTIVES: The objective of this retrospective study was to quantify the clinical and economic burden of significant bleeding in lung resection surgery in the US. METHODS: This study utilized 2009-2012 data from the Premier Perspective DatabaseTM. Adult patients with primary pulmonary lobectomy or segmentectomy procedures were categorized by the surgical approach (VATS vs open) and primary diagnosis (primary or metastatic lung cancer vs non-lung cancer). Patients requiring >=3 units of blood products with at least 1 unit of PRBCs: "significant bleeding" cohort; those requiring <3 units: "non-significant bleeding" cohort; and those not requiring blood products: "no bleeding" cohort. A matched cohort analysis was performed between the "significant bleeding" and the "no bleeding cohort" using matching variables: hospital, lung cancer diagnosis, year of surgery, APR-DRG severity score, procedure type and approach, age, and gender. RESULTS: The "All-patient" cohort comprised 21,429 patients: 213 "significant bleeding"; 2,780 "non-significant bleeding"; and 18,436 "no bleeding". Overall incidence of significant chest bleeding was 0.99%. Patients from "significant bleeding" cohort and "non-significant bleeding" cohort had 2.5 days and 2 days (p < 0.0001) longer length of stay in the hospital compared to those in the "no bleeding" cohort, respectively. Overall, hospital costs for "significant bleeding" cohort were higher than "no bleeding" cohort for those who were covered under Medicare ($59,871 vs $23,641), were >=76 years of age ($64,010 vs $24,243), had greater severity of illness ($97,813 vs $51,871) and underwent open segmentectomy ($74,220 vs $21,903). Hospital costs for "significant bleeding" cohort and "non-significant bleeding" were significantly higher ($11,589 and $5,280, respectively, p < 0.0001) than no bleeding cohort. CONCLUSIONS: Although significant bleeding during lung resection surgery is rare, patients with such complication could stay longer at the hospital and cost an average of $13,103 more than those without. PMID- 27266754 TI - Effect of the addition of rituximab to salvage chemotherapy prior to autologous stem cell transplant in aggressive CD20+ lymphoma: a cohort comparison from the NCIC Clinical Trials Group Study LY.12. AB - The impact of the addition of rituximab to salvage chemotherapy prior to autologous stem cell transplant (ASCT) was evaluated in a retrospective subgroup analysis of NCIC CTG LY.12. Among 414 patients who relapsed following R-CHOP, 96 received salvage chemotherapy alone [R - cohort]; and 318 received rituximab with chemotherapy [R + cohort] following a protocol amendment. The R-cohort had a higher proportion of patients with PS >=2 and relapse <1 year after R-CHOP. The response rate (45.6% vs. 25.0%, p = 0.0003), CR/CRu (15.7% vs. 4.2%, p = 0.003) and transplantation rate (51.9% vs. 31.3%, p = 0.0004) was higher in the R + cohort. Event-free (27% vs. 22%, p = 0.0954) and overall survival at four years (43% vs. 31%; p = 0.045) were greater in the R + cohort when the patients with best response SD/PD to R-CHOP were excluded. Addition of rituximab to salvage therapy before ASCT appears to improve the response rate, transplantation rate, and overall survival in patients with CD20+ lymphoma who responded to R-CHOP. PMID- 27266759 TI - GPU-Accelerated State-Averaged Complete Active Space Self-Consistent Field Interfaced with Ab Initio Multiple Spawning Unravels the Photodynamics of Provitamin D3. AB - Excited-state molecular dynamics is essential to the study of photochemical reactions, which occur under nonequilibrium conditions. However, the computational cost of such simulations has often dictated compromises between accuracy and efficiency. The need for an accurate description of both the molecular electronic structure and nuclear dynamics has historically stymied the simulation of medium- to large-size molecular systems. Here, we show how to alleviate this problem by combining ab initio multiple spawning (AIMS) for the nuclear dynamics and GPU-accelerated state-averaged complete active space self consistent field (SA-CASSCF) for the electronic structure. We demonstrate the new approach by first-principles SA-CASSCF/AIMS nonadiabatic dynamics simulation of photoinduced electrocyclic ring-opening in the 51-atom provitamin D3 molecule. PMID- 27266767 TI - Elucidating the molecular mechanisms underlying cellular response to biophysical cues using synthetic biology approaches. AB - The use of synthetic surfaces and materials to influence and study cell behavior has vastly progressed our understanding of the underlying molecular mechanisms involved in cellular response to physicochemical and biophysical cues. Reconstituting cytoskeletal proteins and interfacing them with a defined microenvironment has also garnered deep insight into the engineering mechanisms existing within the cell. This review presents recent experimental findings on the influence of several parameters of the extracellular environment on cell behavior and fate, such as substrate topography, stiffness, chemistry and charge. In addition, the use of synthetic environments to measure physical properties of the reconstituted cytoskeleton and their interaction with intracellular proteins such as molecular motors is discussed, which is relevant for understanding cell migration, division and structural integrity, as well as intracellular transport. Insight is provided regarding the next steps to be taken in this interdisciplinary field, in order to achieve the global aim of artificially directing cellular response. PMID- 27266768 TI - Identifying improvements to complex pathways: evidence synthesis and stakeholder engagement in infant congenital heart disease. AB - OBJECTIVES: Many infants die in the year following discharge from hospital after surgical or catheter intervention for congenital heart disease (3-5% of discharged infants). There is considerable variability in the provision of care and support in this period, and some families experience barriers to care. We aimed to identify ways to improve discharge and postdischarge care for this patient group. DESIGN: A systematic evidence synthesis aligned with a process of eliciting the perspectives of families and professionals from community, primary, secondary and tertiary care. SETTING: UK. RESULTS: A set of evidence-informed recommendations for improving the discharge and postdischarge care of infants following intervention for congenital heart disease was produced. These address known challenges with current care processes and, recognising current resource constraints, are targeted at patient groups based on the number of patients affected and the level and nature of their risk of adverse 1-year outcome. The recommendations include: structured discharge documentation, discharging certain high-risk patients via their local hospital, enhanced surveillance for patients with certain (high-risk) cardiac diagnoses and an early warning tool for parents and community health professionals. CONCLUSIONS: Our recommendations set out a comprehensive, system-wide approach for improving discharge and postdischarge services. This approach could be used to address challenges in delivering care for other patient populations that can fall through gaps between sectors and organisations. PMID- 27266769 TI - Default options in advance directives: study protocol for a randomised clinical trial. AB - INTRODUCTION: Although most seriously ill Americans wish to avoid burdensome and aggressive care at the end of life, such care is often provided unless patients or family members specifically request otherwise. Advance directives (ADs) were created to provide opportunities to set limits on aggressive care near life's end. This study tests the hypothesis that redesigning ADs such that comfort oriented care is provided as the default, rather than requiring patients to actively choose it, will promote better patient-centred outcomes. METHODS AND ANALYSIS: This multicentre trial randomises seriously ill adults to receive 1 of 3 different ADs: (1) a traditional AD that requires patients to actively choose their goals of care or preferences for specific interventions (eg, feeding tube insertion) or otherwise have their care guided by their surrogates and the prevailing societal default toward aggressive care; (2) an AD that defaults to life-extending care and receipt of life-sustaining interventions, enabling patients to opt out from such care; or (3) an AD that defaults to comfort care, enabling patients to opt into life-extending care. We seek to enrol 270 patients who return complete, legally valid ADs so as to generate sufficient power to detect differences in the primary outcome of hospital-free days (days alive and not in an acute care facility). Secondary outcomes include hospital and intensive care unit admissions, costs of care, hospice usage, decision conflict and satisfaction, quality of life, concordance of preferences with care received and bereavement outcomes for surrogates of patients who die. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Boards at all trial centres, and is guided by a data safety and monitoring board and an ethics advisory board. Study results will be disseminated using methods that describe the results in ways that key stakeholders can best understand and implement. TRIAL REGISTRATION NUMBER: NCT02017548; Pre-results. PMID- 27266770 TI - When procedures meet practice in community pharmacies: qualitative insights from pharmacists and pharmacy support staff. AB - OBJECTIVES: Our aim was to explore how members of community pharmacy staff perceive and experience the role of procedures within the workplace in community pharmacies. SETTING: Community pharmacies in England and Wales. PARTICIPANTS: 24 community pharmacy staff including pharmacists and pharmacy support staff were interviewed regarding their view of procedures in community pharmacy. Transcripts were analysed using thematic analysis. RESULTS: 3 main themes were identified. According to the 'dissemination and creation of standard operating procedures' theme, community pharmacy staff were required to follow a large amount of procedures as part of their work. At times, complying with all procedures was not possible. According to the 'complying with procedures' theme, there are several factors that influenced compliance with procedures, including work demands, the high workload and the social norm within the pharmacy. Lack of staff, pressure to hit targets and poor communication also affected how able staff felt to follow procedures. The third theme 'procedural compliance versus using professional judgement' highlighted tensions between the standardisation of practice and the professional autonomy of pharmacists. Pharmacists feared being unsupported by their employer for working outside of procedures, even when acting for patient benefit. Some support staff believed that strictly following procedures would keep patients and themselves safe. Dispensers described following the guidance of the pharmacist which sometimes meant working outside of procedures, but occasionally felt unable to voice concerns about not working to rule. CONCLUSIONS: Organisational resilience in community pharmacy was apparent and findings from this study should help to inform policymakers and practitioners regarding factors likely to influence the implementation of procedures in community pharmacy settings. Future research should focus on exploring community pharmacy employees' intentions and attitudes towards rule-breaking behaviour and the impact this may have on patient safety. PMID- 27266771 TI - Comparing cognitive-behavioural psychotherapy and psychoeducation for non specific symptoms associated with indoor air: a randomised control trial protocol. AB - INTRODUCTION: Indoor air-related conditions share similarities with other conditions that are characterised by medically unexplained symptoms (MUS)-a combination of non-specific symptoms that cannot be fully explained by structural bodily pathology. In cases of indoor air-related conditions, these symptoms are not fully explained by either medical conditions or the immunological toxicological effects of environmental factors. The condition may be disabling, including a non-adaptive health behaviour. In this multifaceted phenomenon, psychosocial factors influence the experienced symptoms. Currently, there is no evidence of clinical management of symptoms, which are associated with the indoor environment and cannot be resolved by removing the triggering environmental factors. The aim of this study is to compare the effect of treatment-as-usual (TAU) and two psychosocial interventions on the quality of life, and the work ability of employees with non-specific indoor air-related symptomatology. METHODS AND ANALYSES: The aim of this ongoing randomised controlled trial is to recruit 60 participants, in collaboration with 5 occupational health service units. The main inclusion criterion is the presence of indoor air-related recurrent symptoms in >=2 organ systems, which have no pathophysiological explanation. After baseline clinical investigations, participants are randomised into interventions, which all include TAU: cognitive-behavioural psychotherapy, psychoeducation and TAU (control condition). Health-related quality of life, measured using the 15D scale, is the primary outcome. Secondary outcomes include somatic and psychiatric symptoms, occupational factors, and related underlying mechanisms (ie, cognitive functioning). Questionnaires are completed at baseline, at 3, 6 and 12-month follow-ups. Data collection will continue until 2017. The study will provide new information on the individual factors related to indoor air-associated symptoms, and on ways in which to support work ability. ETHICS AND DISSEMINATION: The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, has granted approval for the study. The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02069002; Pre-results. PMID- 27266773 TI - Clinical outcomes at 12 months and risk of inflammatory bowel disease in patients with an intermediate raised fecal calprotectin: a 'real-world' view. AB - OBJECTIVES: A recent systematic review confirmed the usefulness of fecal calprotectin (FC) in distinguishing organic (inflammatory bowel disease (IBD)) from non-organic gastrointestinal disease (irritable bowel syndrome (IBS)). FC levels <50 MUg/g have a negative predictive value >92% to exclude organic gastrointestinal (GI) disease. Levels >250 MUg/g correlate with endoscopic IBD disease activity; sensitivity 90%. We aimed to determine clinical outcomes in intermediate raised FC results (50-250 MUg/g). SETTING: Primary care general practices in Coventry and Warwickshire, and 3 secondary care hospitals. PARTICIPANTS: 443 FC results in adults (>16 years old) were reviewed from July 2012 to October 2013. Clinical data was collected from hospital databases and general practitioners. Long-term clinical data was available in 41 patients (out of 48). PRIMARY AND SECONDARY OUTCOME MEASURES: The number of new diagnoses of IBD, IBS and other diagnoses for the intermediate group. The number referred and discharged from secondary care. RESULTS: A new IBD diagnosis was made in 19% (n=8) of intermediate results (1% of normal and 38% of raised results). 5% (n=2) of intermediate results had known IBD in remission. A new IBS diagnosis was made in 27% (n=11) of intermediate results, while 34% (n=14) remained undiagnosed, although 8 of these were not referred to secondary care. CONCLUSIONS: FC testing remains useful in aiding diagnosis of organic GI conditions. However, unlike negative and strongly positive FC results, intermediate FC results lead to a mixture of diagnoses. The OR of a new diagnosis of IBD for an intermediate result compared to normal FC result was 26.6, while an intermediate FC result gave an OR of 0.54 for a new IBS diagnosis compared to normal FC. For intermediate FC results, 1 in 3 patients remained in secondary care after 12 months with an OR of 3.6 compared to a normal FC result. PMID- 27266772 TI - Validation of the Kinyarwanda-version Short-Form Leeds Dyspepsia Questionnaire and Short-Form Nepean Dyspepsia Index to assess dyspepsia prevalence and quality of-life impact in Rwanda. AB - OBJECTIVES: We aimed to develop and validate Kinyarwanda versions of Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) and Short-Form Nepean Dyspepsia Index (SF NDI) to measure the frequency and severity of dyspepsia and associated quality-of life impact in Rwanda. SETTING: A single, tertiary care centre in Rwanda. PARTICIPANTS: 200 consecutive Kinyarwanda-speaking patients referred to endoscopy (100 patients) or medical outpatients (100 patients). INTERVENTIONS: Kinyarwanda versions of the SF-LDQ and SF-NDI were developed from English versions by translation, with back translation, crosschecking and pilot testing. Study participants completed these questionnaires at enrolment (time 1), and then completed the surveys again with blinded phone interviewers 3 days later (time 2). 20 randomly selected participants, diagnosed with a peptic ulcer on index endoscopy, completed a third survey by phone at day 30 (time 3), after therapy. PRIMARY OUTCOME MEASURES: Internal consistency at time 1 (by Cronbach's alpha) and test-retest reliability between time 1 and time 2 (Spearman's correlation coefficient) for translated SF-LDQ and SF-NDI; validity versus clinical diagnosis (by receiver operating characteristic (ROC) curve) and responsiveness to treatment for SF-LDQ (by change in mean score). All outcomes were measured as per protocol. RESULTS: Cronbach's alpha of the translated SF-LDQ was 0.93, showing high internal consistency. Spearman's correlation coefficient comparing time 1 and time 2 was 0.978 (p<0.001), demonstrating high reliability. Cronbach's alpha for the translated SF-NDI was 0.92. A cut-off score of 16 on the SF-LDQ showed a sensitivity of 97% and a specificity of 71% for the diagnosis of dyspepsia, correctly classifying 89% of patients. In the responsiveness analysis, the mean SF-LDQ score was reduced from 20.1 prior to treatment to 13.9 after 30 days of treatment (p=0.003). CONCLUSIONS: The Kinyarwanda versions of the SF-LDQ and SF NDI were valid, reliable and responsive to treatment. PMID- 27266774 TI - Electronic nicotine delivery system landscape in licensed tobacco retailers: results of a county-level survey in Oklahoma. AB - OBJECTIVES: Electronic nicotine delivery systems (ENDS) have recently emerged as a component of the tobacco retail environment. The aims of this study were to describe the availability, types of ENDS and placement of ENDS relative to traditional tobacco products at franchised licensed tobacco retailers and non franchised licensed tobacco retailers. DESIGN: Observational study. SETTING: Franchised and non-franchised tobacco retailers in Cleveland County, Oklahoma, USA. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of stores selling ENDS, the variability in brands of ENDS sold, the location of the ENDS within the retailers, the quantity of ENDS sold compared with traditional tobacco products, and the presence of outdoor signage. RESULTS: Data from 57 randomly sampled tobacco retailers were used to describe the presence of ENDS at independent non franchised and franchised tobacco retailers. The overwhelming majority (90%) of licensed tobacco retailers sold ENDS, and differences were observed between franchised and non-franchised stores. 45 of the 51 retailers (88%) selling ENDS had them placed at the point of sale. 2 of the 21 franchised retailers (9.5%) had ENDS placed at <=31/2 feet above floor level compared to none of the 30 non franchised retailers (0%). CONCLUSIONS: This small study is the first to characterise ENDS within the tobacco retail environment in a county in Oklahoma, USA. The results from this study demonstrate the complexity of the tobacco retail landscape and generate questions for future studies regarding the incorporation and placement of ENDS in tobacco retail environments. PMID- 27266775 TI - Longitudinal trends in use and costs of targeted therapies for common cancers in Taiwan: a retrospective observational study. AB - OBJECTIVES: Some targeted therapies have improved survival and overall quality of cancer care generally, but these increasingly expensive medicines have led to increases in pharmaceutical expenditure. This study examined trends in use and expenditures of antineoplastic agents in Taiwan, and estimated market shares by prescription volume and costs of targeted therapies over time. We also determined which cancer types accounted for the highest use of targeted therapies. DESIGN: This is a retrospective observational study focusing on the utilisation of targeted therapies for treatment of cancer. SETTING: The monthly claims data for antineoplastic agents were retrieved from Taiwan's National Health Insurance Research Database (2009-2012). MAIN OUTCOME MEASURES: We calculated market shares by prescription volume and costs for each class of antineoplastic agent by cancer type. Using a time series design with Autoregressive Integrated Moving Average (ARIMA) models, we estimated trends in use and costs of targeted therapies. RESULTS: Among all antineoplastic agents, use of targeted therapies grew from 6.24% in 2009 to 12.29% in 2012, but their costs rose from 26.16% to 41.57% in that time. Monoclonal antibodies and protein kinase inhibitors contributed the most (respectively, 23.84% and 16.12% of costs for antineoplastic agents in 2012). During 2009-2012, lung (44.64% of use; 28.26% of costs), female breast (16.49% of use; 27.18% of costs) and colorectal (12.11% of use; 13.16% of costs) cancers accounted for the highest use of targeted therapies. CONCLUSIONS: In Taiwan, targeted therapies are increasingly used for different cancers, representing a substantial economic burden. It is important to establish mechanisms to monitor their use and outcomes. PMID- 27266798 TI - A more general model for testing measurement invariance and differential item functioning. AB - The evaluation of measurement invariance is an important step in establishing the validity and comparability of measurements across individuals. Most commonly, measurement invariance has been examined using 1 of 2 primary latent variable modeling approaches: the multiple groups model or the multiple-indicator multiple cause (MIMIC) model. Both approaches offer opportunities to detect differential item functioning within multi-item scales, and thereby to test measurement invariance, but both approaches also have significant limitations. The multiple groups model allows 1 to examine the invariance of all model parameters but only across levels of a single categorical individual difference variable (e.g., ethnicity). In contrast, the MIMIC model permits both categorical and continuous individual difference variables (e.g., sex and age) but permits only a subset of the model parameters to vary as a function of these characteristics. The current article argues that moderated nonlinear factor analysis (MNLFA) constitutes an alternative, more flexible model for evaluating measurement invariance and differential item functioning. We show that the MNLFA subsumes and combines the strengths of the multiple group and MIMIC models, allowing for a full and simultaneous assessment of measurement invariance and differential item functioning across multiple categorical and/or continuous individual difference variables. The relationships between the MNLFA model and the multiple groups and MIMIC models are shown mathematically and via an empirical demonstration. (PsycINFO Database Record PMID- 27266799 TI - Measurement invariance via multigroup SEM: Issues and solutions with chi-square difference tests. AB - Multigroup structural equation modeling (SEM) plays a key role in studying measurement invariance and in group comparison. When population covariance matrices are deemed not equal across groups, the next step to substantiate measurement invariance is to see whether the sample covariance matrices in all the groups can be adequately fitted by the same factor model, called configural invariance. After configural invariance is established, cross-group equalities of factor loadings, error variances, and factor variances-covariances are then examined in sequence. With mean structures, cross-group equalities of intercepts and factor means are also examined. The established rule is that if the statistic at the current model is not significant at the level of .05, one then moves on to testing the next more restricted model using a chi-square-difference statistic. This article argues that such an established rule is unable to control either Type I or Type II errors. Analysis, an example, and Monte Carlo results show why and how chi-square-difference tests are easily misused. The fundamental issue is that chi-square-difference tests are developed under the assumption that the base model is sufficiently close to the population, and a nonsignificant chi-square statistic tells little about how good the model is. To overcome this issue, this article further proposes that null hypothesis testing in multigroup SEM be replaced by equivalence testing, which allows researchers to effectively control the size of misspecification before moving on to testing a more restricted model. R code is also provided to facilitate the applications of equivalence testing for multigroup SEM. (PsycINFO Database Record PMID- 27266776 TI - Effect of affordable technology on physical activity levels and mobility outcomes in rehabilitation: a protocol for the Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial. AB - INTRODUCTION: People with mobility limitations can benefit from rehabilitation programmes that provide a high dose of exercise. However, since providing a high dose of exercise is logistically challenging and resource-intensive, people in rehabilitation spend most of the day inactive. This trial aims to evaluate the effect of the addition of affordable technology to usual care on physical activity and mobility in people with mobility limitations admitted to inpatient aged and neurological rehabilitation units compared to usual care alone. METHODS AND ANALYSIS: A pragmatic, assessor blinded, parallel-group randomised trial recruiting 300 consenting rehabilitation patients with reduced mobility will be conducted. Participants will be individually randomised to intervention or control groups. The intervention group will receive technology-based exercise to target mobility and physical activity problems for 6 months. The technology will include the use of video and computer games/exercises and tablet applications as well as activity monitors. The control group will not receive any additional intervention and both groups will receive usual inpatient and outpatient rehabilitation care over the 6-month study period. The coprimary outcomes will be objectively assessed physical activity (proportion of the day spent upright) and mobility (Short Physical Performance Battery) at 6 months after randomisation. Secondary outcomes will include: self-reported and objectively assessed physical activity, mobility, cognition, activity performance and participation, utility based quality of life, balance confidence, technology self-efficacy, falls and service utilisation. Linear models will assess the effect of group allocation for each continuously scored outcome measure with baseline scores entered as a covariate. Fall rates between groups will be compared using negative binomial regression. Primary analyses will be preplanned, conducted while masked to group allocation and use an intention-to-treat approach. ETHICS AND DISSEMINATION: The protocol has been approved by the relevant Human Research Ethics Committees and the results will be disseminated widely through peer-reviewed publication and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12614000936628. Pre results. PMID- 27266800 TI - Synthesis and Characterization of (89)Zr-Labeled Ultrasmall Nanoparticles. AB - The ultrasmall nanoparticle AGuIX is a versatile platform that tolerates a range of chemical diversity for theranostic applications. Our previous work showed that AGuIX clears rapidly from normal tissues, while durably accumulating within the tumor microenvironment. On this basis, AGuIX was used to detect tumor tissue with Gd(3+) enhanced MRI and can sensitize tumors to radiation therapy. As we begin the translation of AGuIX, we appreciated that coupling AGuIX to a long-lived radioisotope would help to more completely measure the magnitude and duration of its retention within the tumor microenvironment. Therefore, we developed (89)Zr DFO-AGuIX. AGuIX was coupled to DFO and then to (89)Zr in ~99% radiochemical yield. Stability studies showed that (89)Zr-DFO-AGuIX did not dissociate after 72 h. In animals bearing U87MG xenografts, it was detectable at levels above background for 72 h. Lastly, (89)Zr-DFO-AGuIX did not accumulate in inflammatory abscesses in vivo, highlighting its specificity for well vascularized tumors. PMID- 27266801 TI - A prospective study of collapsing focal segmental glomerulosclerosis. AB - Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by rapid progression to end-stage renal disease (ESRD). We evaluated the clinicopathological spectrum of cFSGS and compared its clinical behavior to steroid and tacrolimus (TAC)-resistant noncollapsing focal segmental glomerulosclerosis (FSGS). All patients (>14 years) diagnosed with cFSGS were enrolled in the study. Staining for differentiated podocyte markers such as WT 1, PAX and KI67 were performed in all patients. The outcome and histological features of cFSGS was compared with a prospectively followed cohort of steroid and TAC-resistant noncollapsing FSGS. The study included 22 cFSGS patients and 19 cases of steroid and TAC-resistant FSGS. Complete remission, partial remission, steroid resistance, progression to ESRD and death were observed in 13.6%, 4.5%, 27.3%, 36.4% and 18.2% patients, respectively. Patients with cFSGS had higher serum creatinine and more advanced tubulointerstitial changes compared to resistant FSGS. Twenty-six percent of therapy resistant noncollapsing FSGS progressed to ESRD after two years of stopping TAC. However, there was no difference in progression to ESRD between cFSGS and therapy-resistant noncollapsing FSGS at the end of two years. Glomerular collapse in the setting of FSGS is poorly responsive to treatment and has a high rate of progression to ESRD. The long-term prognosis of cFSGS and steroid and TAC-resistant FSGS are similar. PMID- 27266802 TI - Expression and Clinical Significance of Metalloproteases and Their Inhibitors by Endothelial Cells From Invasive Breast Carcinomas. AB - BACKGROUND: Given that tumor blood vessels are important in tumor progression and metastasis, tumor endothelial cells (ECs) are the main targets of antiangiogenic therapy. The aim of the present work was to evaluate the phenotype of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) from ECs at the tumor center and its relationship to MMP/TIMP global expression and its relationship to the occurrence of distant metastasis. PATIENTS AND METHODS: An immunohistochemical study was performed using tissue arrays and specific antibodies against MMPs (MMP-2, -7, -9, -11, -13, and -14) and TIMPs (TIMP-1, -2, and -3) at the tumor center in 104 patients with primary ductal invasive breast tumors. RESULTS: MMP-11 expression by ECs was related to shorter relapse-free survival, whereas TIMP-3 expression was related to low occurrence of distant metastasis. In addition, MMP-11 and TIMP-2 expression by ECs was associated with shorter overall survival, whereas TIMP-3 expression by ECs was associated with longer overall survival. Our findings indicate significant relationships between the expression of MMPs/TIMPs by ECs and the global expression of these factors at the tumor scene. CONCLUSION: High MMP/TIMP expression by ECs from breast carcinomas, which may be consequence of the cross-talk between tumor cells and their surrounding microenvironment. PMID- 27266803 TI - Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer. AB - BACKGROUND: Recent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. MATERIALS AND METHODS: A customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). RESULTS: A total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further axillary involvement, with no difference between the academic and community radiation oncologists (P = .11). CONCLUSION: In SLN biopsy-positive early-stage breast cancer with omission of completion ALND, axillary RT is increasing used to cover the undissected axilla. Most respondents use SCF or AX for patients with low to intermediate pathologic features. Online prediction nomograms are used by a few practitioners to assist in clinical decision-making in this setting. PMID- 27266804 TI - Phase 2 Study of Trabectedin in Patients With Hormone Receptor-Positive, HER-2 Negative, Advanced Breast Carcinoma According to Expression of Xeroderma Pigmentosum G Gene. AB - BACKGROUND: Preclinical and clinical data suggest that xeroderma pigmentosum G gene (XPG) status might predict trabectedin efficacy. This phase 2 study evaluated the efficacy of trabectedin at a dose of 1.3 mg/m2 as a 3-hour intravenous infusion every 3 weeks in hormone receptor-positive, HER-2 (human epidermal growth factor receptor 2)-negative, advanced breast cancer patients according to the tumor level of XPG mRNA expression. PATIENTS AND METHODS: Patients were stratified into high-XPG (>3) or low-XPG (<= 3) groups. The primary efficacy end point was progression-free survival (PFS) rate at 16 weeks (PFS4); secondary efficacy end points were overall response rate (ORR), duration of response, PFS, overall survival, and safety of trabectedin in this patient population. RESULTS: Forty-four patients were treated, 21 with high XPG and 23 with low XPG. Four high-XPG and 6 low-XPG patients experienced PFS4; the criterion for further recruitment (> 6 patients experienced PFS4) was thus not met, and recruitment was stopped. One high-XPG patient had a partial response (ORR, 5%). One low-XPG patient had a complete response, and 2 low-XPG patients had partial responses (ORR, 13%). Comparison of efficacy parameters between high XPG and low-XPG patients showed no statistically significant differences. ORR in the efficacy population was 9.3%, median PFS was 1.9 months, and overall survival was 11.8 months. The safety of trabectedin in breast carcinoma was similar to that shown in other indications. CONCLUSION: Trabectedin as single agent had limited activity in hormone-positive, HER-2-negative advanced breast cancer. XPG mRNA expression was not predictive of trabectedin efficacy. PMID- 27266805 TI - How important is coronary artery disease when considering lung transplant candidates? AB - BACKGROUND: Coronary artery disease (CAD) remains a relative contraindication for lung transplantation, but should it be if amenable to effective palliation? METHODS: From January 2005 to July 2010, 356 adults undergoing primary lung transplantation had no significant (<50%) coronary arterial stenosis and 70 had significant (>=50%) CAD requiring prior or concomitant revascularization. Propensity matching on 38 pre-transplant patient characteristics identified 61 well-matched pairs (87% of possible matches) and 295 no-CAD unmatched patients to compare post-operative morbidity, graft function, and time-related pulmonary function and survival. RESULTS: Compared with no-CAD patients, those with CAD intervention were older, more likely to be male, had more comorbidities, and were more likely to have idiopathic pulmonary fibrosis. Among propensity-matched patients, 5 died in-hospital in the CAD intervention group and 6 in the no-CAD group (p = 0.7). Intensive care unit stay (5 vs 7 days), post-operative stay (14 vs 15 days), tracheostomy requirement (12 vs 11 patients), primary graft dysfunction scores (p >0.8), and early longitudinal post-transplant pulmonary function (p = 0.2) were similar, as was time-related mortality (20% vs 22% and 51% vs 52% at 1 and 4 years, respectively; p = 0.6). Unmatched no-CAD patients had fewer comorbidities and lower mortality than matched patients (15% and 39% at 1 and 4 years, respectively; p = 0.01). CONCLUSIONS: CAD is an important risk factor in lung transplant candidates, but its influence can be minimized in experienced centers by effective palliation. Surprisingly, however, CAD is a marker for an unfavorable patient phenotype with worse than typical post transplant survival, irrespective of whether CAD is present. PMID- 27266806 TI - Biventricular response to pulmonary artery banding in children with dilated cardiomyopathy. PMID- 27266807 TI - Breast Cancer-Related Arm Lymphedema: Fluctuation over Six Months and the Effect of the Weather. AB - BACKGROUND: An understanding of normal fluctuation of lymphedema over time is important to identify real change, whether it is from response to treatment or worsening of the condition. The weather is another factor that possibly influences lymphedema but has had minimal investigation to date. The purpose of this study was to determine the extent to which breast cancer-related lymphedema (BCRL) fluctuated over a 6-month period and the influence of temperature, humidity, and barometric pressure. METHOD AND RESULTS: Women with unilateral BCRL (n = 26) and without BCRL (n = 17) were measured on nine occasions over 6 months using a standardized protocol. Measures included self-reported arm swelling, arm volume, and extracellular fluid with bioimpedance. Daily weather data were obtained for analysis of effects on lymphedema. Neither arm volume nor extracellular fluid varied significantly for women with lymphedema; coefficients of variation were 2.3% and 3.7%, respectively. Women without lymphedema had even less fluctuation, with coefficient of variation of 1.9% for arm volume and 2.9% for ECF. Correlation of weather and lymphedema data showed that temperature was the only aspect of the weather to have any effect on BCRL, with the maximum temperature on the day before measurement slightly affecting ECF (r = 0.27, p < 0.001), arm volume (r = 0.23, p < 0.001), and self-reported swelling (r = 0.26, p < 0.001). For women without lymphedema, the weather did not affect any measure. CONCLUSIONS: Established BCRL is relatively stable over a 6-month period. Temperature was the only aspect of the weather found to impact lymphedema. PMID- 27266808 TI - Advances in hemophilia and the role of current and emerging prophylaxis. AB - The primary goal of hemophilia treatment and management is the prevention of painful, disabling, and costly joint arthropathy that results from its characteristic bleeding into joints and muscles. Prophylactic treatment with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is, therefore, the standard of care for hemophilia A and B. Data has demonstrated the clinical efficacy and overall benefits of prophylaxis in young children, adolescents, and adults. Early initiation with prima-ry prophylaxis is ideal, but secondary prophylaxis in adolescents and adults has also demonstrated significant success. Because the standard of care includes prophylaxis with factor concentrate replacement in order to prevent joint damage in patients with hemophilia, prophylaxis is now more common and needs to be addressed in all clinical settings, including managed care. However, further research is needed to help clinicians develop individualized factor-replacement protocols and under stand the impact of long-term use into adulthood. World Federation of Hemophilia guidelines do not have definitive recommendations on continuation of prophylaxis into adulthood. The optimal regimen for initiating prophylaxis, duration of treatment, and dosing regimens continue to be studied. PMID- 27266809 TI - Economic costs of hemophilia and the impact of prophylactic treatment on patient management. AB - Hemophilia is a rare congenital bleeding disorder characterized by spontaneous and potentially life-threatening bleeding episodes. In addition to its clinical burden on the patient, the condition also places a significant economic burden on healthcare payers, patients/caregivers, and society. Hemophilia is associated with staggering direct costs from hospitalizations, outpatient visits, and drug treatments, as well as high indirect costs from diminished work productivity and absenteeism from work and school. Additionally, hemophilia incurs tremendous intangible costs, including reduced quality of life, pain and suffering, and the emotional and physical toll on the patient and caregivers. The evolution of treatment patterns in hemophilia has transformed the once-fatal disease into a chronic but potentially well-managed condition through the use of prophylaxis treatment. However, other complications, such as development of inhibitory antibodies, have added to the complexity of managing the disease and its costs. To ensure optimal treatment outcomes and disease management, there is a critical need to understand the utilization of healthcare resources in the treatment of hemophilia and to educate patients on the importance of treatment adherence and compliance to reduce long-term effects on musculoskeletal health. PMID- 27266810 TI - Differentiation of functional endothelial cells from human induced pluripotent stem cells: A novel, highly efficient and cost effective method. AB - Endothelial cells derived from human induced pluripotent stem cells (hiPSC- EC) are of significant value for research on human vascular development, in vitro disease models and drug screening. Here we report an alternative, highly efficient and cost-effective simple three step method (mesoderm induction, endothelial cell differentiation and endothelial cell expansion) to differentiate hiPSC directly into endothelial cells. We demonstrate that efficiency of described method to derive CD31+ and VE-Cadherin+ double positive cells is higher than 80% in 12 days. Most notably we established that hiPSC-EC differentiation efficacy depends on optimization of both mesoderm differentiation and endothelial cell differentiation steps. PMID- 27266811 TI - Identification of vector-borne pathogens in dogs and cats from Southern Brazil. AB - Dogs and cats are often infected with vector-borne pathogens and play a crucial role as reservoirs and hosts in their life cycles. The aim of the present study was to investigate the occurrence of vector-borne pathogens among dogs and cats in the northwestern region of Rio Grande do Sul (RS) State, Brazil. One hundred and ten blood samples were collected from dogs (n=80) and cats (n=30). Laboratory analysis were carried out through stained blood smears, indirect enzyme-linked immunosorbent assay (ELISA) for Babesia vogeli and Ehrlichia canis (only for dogs) and polymerase chain reaction (PCR) aiming the detection of pathogens. The following pathogens were screened by PCR among dogs and cats: Babesia spp. and Hepatozoon spp. (18S rRNA gene), Anaplasma spp. (16S rRNA gene), and Ehrlichia spp. (dsb gene for dogs and 16S rRNA gene for cats) and Bartonella spp. (nuoG gene only for cats). Using blood smears structures morphologically compatible with piroplasms were found in 5.45% (6/110) of the samples. Anti-B. vogeli and anti-E. canis antibodies were detected in 91% (73/80) and 9% (7/80) of the dogs, respectively. All the seropositive dogs to E. canis were also to B. vogeli. Nineteen (17.3%) animals were positive to hemoparasites by PCR. After sequencing Rangelia vitalii 6/80 (7.5%), B. vogeli 3/80 (4%), Hepatozoon spp. 1/80 (1%), and Anaplasma spp. 1/80 (1%) were found in the dogs, and B. vogeli 2/30 (7%) and Bartonella spp. 6/30 (20%) were detected in the screened cats. No sample was positive for genes dsb and 16S rRNA of Ehrlichia spp. Only those animals which were positive for R. vitalii showed findings compatible with rangeliosis, such as anemia (100%), thrombocytopenia (67%), jaundice (50%), external bleeding (50%), and anorexia (50%). This is the first time that B. vogeli detected among cats in Southern Brazil. PMID- 27266813 TI - How Should Risk-Based Regulation Reflect Current Public Opinion? AB - Risk-based regulation of novel agricultural products with public choice manifest via traceability and labelling is a more effective approach than the use of regulatory processes to reflect public concerns, which may not always be supported by evidence. PMID- 27266812 TI - Inhibition of vascular endothelial growth factor reduces cardiac allograft vasculopathy. AB - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a leading expression of chronic organ rejection at and beyond 1 year post-transplantation. Host bone marrow (BM)-derived cell migration to the allograft has been demonstrated in earlier work. Vascular endothelial growth factor (VEGF) is endogenously overexpressed within allografts. Graft neo-angiogenesis has been proposed as a mechanism by which VEGF may contribute to CAV. Herein we assess the therapeutic effect of inhibition of VEGF expression in CAV. METHODS: In 129J mice, female donor hearts were heterotopically transplanted into C57/B16 males and treated with soluble VEGF receptor 1 (sVEGFR1) or vehicle control. The effect of VEGF inhibition on BM-mediated microvascular outgrowth and endothelial cell migration and proliferation were assessed using in vitro assays of aortic ring angiogenesis, wound healing and proliferation, respectively. RESULTS: At 21 days post-transplantation, treatment with sVEGFR1 significantly reduced both percent luminal narrowing (p < 0.05) and percent of vessels affected (p < 0.005). sVEGFR1 significantly reduced average wet heart weight (p < 0.05), whereas mean ventricular cross-sectional area remained similar. Treatment of aortic rings with both sVEGFR1 and VEGFR2 tyrosine phosphorylation inhibitor (Ki 8751) significantly reduced BM-mediated microvascular outgrowth length (p < 0.05) and area (p < 0.05). Treatment of human coronary artery endothelial cells with sVEGFR1 and Ki 8751 significantly reduced BM-mediated endothelial cell migration (p < 0.005) and proliferation (p < 0.05). CONCLUSIONS: VEGF inhibition reduces the severity and incidence of CAV in mouse models of cardiac transplantation, while attenuating myocardial edema and neo-angiogenesis. Using this model, we provide in vitro evidence of the role of VEGF signaling in BM-mediated microvascular outgrowth and endothelial cell migration and proliferation. VEGF inhibition may represent a novel approach to CAV treatment and prevention. PMID- 27266814 TI - Effector Molecules and Regulatory Proteins: Applications. AB - Bacteria respond to their external environment by modulating gene expression in the presence of certain effector molecules. The adaptive responses are mediated by transcriptional regulators that, after binding to the DNA, recognize these effector molecules and modify transcription. Some applications of regulatory proteins are reviewed here. PMID- 27266815 TI - AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves' disease and a systematic literature review. AB - Autoimmune Regulator (AIRE) is a transcriptional regulator that is crucial for establishing central tolerance as illustrated by the Mendelian Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome associated with AIRE-inactivating recessive or dominant mutations. Polymorphisms in AIRE have been proposed to be implicated in genetic susceptibility to non-Mendelian organ specific autoimmune diseases. Because there is evidence that in predisposition to Graves' disease (GD) central tolerance is crucial, we investigated whether AIRE polymorphisms could modulate risk of GD. A case-control association study using 29 variants and conducted in 150 GD patients and 200 controls did not detect any significant association. This result is not exceptional: a systematic review of the literature, including GWAS, on the association of AIRE variants with organ specific autoimmune diseases did not show clear associations; similarly heterozygous recessive mutations are not associated to non-Mendelian autoimmunity. Dominant negative mutations of AIRE are associated to autoimmunity but as mild forms of APECED rather than to non-Mendelian organ specific autoimmunity. The lack of association of common AIRE polymorphisms with polygenic autoimmune diseases is counterintuitive as many other genes less relevant for immunological tolerance have been found to be associated. These findings give rise to the intriguing possibility that evolution has excluded functionally modifying polymorphisms in AIRE. PMID- 27266816 TI - Extended lymphadenectomy in elderly and/or highly co-morbid gastric cancer patients: A retrospective multicenter study. AB - BACKGROUND: Gastrectomy with extended lymphadenectomy is considered the gold standard treatment for advanced gastric cancer, with no age- or comorbidity related limitations. We evaluated the safety and efficacy of curative gastrectomy with extended nodal dissection, verifying survival in elderly and highly co morbid patients. METHODS: In a retrospective multicenter study, we examined 1322 non-metastatic gastric-cancer patients that underwent curative gastrectomy with D2 versus D1 lymphadenectomy from January 2000 to December 2009. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) according to age and the Charlson Comorbidity Score were analyzed in relation to the extent of lymphadenectomy. RESULTS: Postoperative morbidity was 30.4%. Complications were more frequent in highly co-morbid elderly patients, and, although general morbidity rates after D2 and D1 lymphadenectomy were similar (29.9% and 33.2%, respectively), they increased following D2 in highly co-morbid elderly patients (39.6%). D2-lymphadenectomy significantly improved 5-year OS and DSS (48.0% vs. 37.6% in D1, p < 0.001 and 72.6% vs. 58.1% in D1, p < 0.001, respectively) in all patients. In elderly patients, this benefit was present only in 5-year DSS. D2 nodal dissection induced better 5-year OS and DSS rates in elderly patients with positive nodes (29.7% vs. 21.2% in D1, p = 0.008 and 47.5% vs. 30.6% in D1, p = 0.001, respectively), although it was present only in DSS when highly co-morbid elderly patients were considered. CONCLUSION: Extended lymphadenectomy confirmed better survival rates in gastric cancer patients. Due to high postoperative complication rate and no significant improvement of the OS, D1 lymphadenectomy should be considered in elderly and/or highly co-morbid gastric cancer patients. PMID- 27266817 TI - The role of surgery for unusual sites of metastases from colorectal cancer: A review of the literature. AB - Although systemic therapy represents the backbone of metastatic colorectal cancer management, surgical resection in selected patients may lead to improved survival, such as observed for hepatic, pulmonary or peritoneal metastases. In regards to surgery for less frequent sites of metastases, far less data are available. The purpose of this article is to review the literature regarding the role of surgery for unusual sites of metastases from colorectal cancer, specifically adrenal, ovarian, and retroperitoneal sites. There are no randomized data to strongly support surgical approach in these scenarios. Despite that, benefit following surgery was suggested in several retrospective studies, with some reports of long-term survival. A careful selection of patients is certainly the key to obtaining better outcomes. Potential characteristics suggesting greater benefit from metastasectomy are isolated site of metastasis, longer disease-free interval from previous treatment, complete resectability, and good performance status. PMID- 27266818 TI - Management of sarcomas possibly involving the knee joint when to perform extra articular resection of the knee joint and is it safe? AB - We reviewed the oncological and functional outcomes of patients treated for a primary sarcoma possibly involving the knee joint and present an algorithm to guide treatment. The records of 76 patients who had a primary bone or soft tissue sarcoma possibly invading the knee between 1996 and 2012 were identified. Mean age and follow-up was 32 years (9-74) and 64 months (12-195), respectively. Patients were grouped according to the resection (Intra-articular [IAR] vs. Extra articular [EAR] vs. Amputation/rotationplasty) for survival and functional outcomes. Overall 5 and 10 year survival was 61% and 53%, respectively. No differences in survival were found between the 3 groups (p = 0.55). Sixteen patients developed local recurrence with no difference between the groups. Mean MSTS score was 24.5 (12-30). Mean flexion at final follow-up was 106 degrees (70 130 degrees ). We conclude that EAR of the knee allows for good oncologic and functional outcomes but with an increased risk of complications compared to IAR. Intra-operative assessment of joint involvement can be done in patients where joint infiltration by the tumour is not clear to avoid an unnecessary EAR. For chondrosarcoma patients with joint involvement, an EAR should be carefully considered because they present a significantly higher local recurrence risk. PMID- 27266819 TI - Superiority of Deformable Image Co-registration in the Integration of Diagnostic Positron Emission Tomography-Computed Tomography to the Radiotherapy Treatment Planning Pathway for Oesophageal Carcinoma. AB - AIMS: To investigate the use of image co-registration in incorporating diagnostic positron emission tomography-computed tomography (PET-CT) directly into the radiotherapy treatment planning pathway, and to describe the pattern of local recurrence relative to the PET-avid volume. MATERIALS AND METHODS: Fourteen patients were retrospectively identified, six of whom had local recurrence. The accuracy of deformable image registration (DIR) and rigid registration of the diagnostic PET-CT and recurrence CT, to the planning CT, were quantitatively assessed by comparing co-registration of oesophagus, trachea and aorta contours. DIR was used to examine the correlation between PET-avid volumes, dosimetry and site of recurrence. RESULTS: Positional metrics including the dice similarity coefficient (DSC) and conformity index (CI), showed DIR to be superior to rigid registration in the co-registration of diagnostic and recurrence imaging to the planning CT. For diagnostic PET-CT, DIR was superior to rigid registration in the transfer of oesophagus (DSC=0.75 versus 0.65, P<0.009 and CI=0.59 versus 0.48, P<0.003), trachea (DSC=0.88 versus 0.65, P<0.004 and CI=0.78 versus 0.51, P<0.0001) and aorta structures (DSC=0.93 versus 0.86, P<0.006 and CI=0.86 versus 0.76, P<0.006). For recurrence imaging, DIR was superior to rigid registration in the transfer of trachea (DSC=0.91 versus 0.66, P<0.03 and CI=0.83 versus 0.51, P<0.02) and oesophagus structures (DSC=0.74 versus 0.51, P<0.004 and CI=0.61 versus 0.37, P<0.006) with a non-significant trend for the aorta (DSC=0.91 versus 0.75, P<0.08 and CI=0.83 versus 0.63, P<0.06) structure. A mean inclusivity index of 0.93 (range 0.79-1) showed that the relapse volume was within the planning target volume (PTVPET-CT); all relapses occurred within the high dose region. CONCLUSION: DIR is superior to rigid registration in the co-registration of PET CT and recurrence CT to the planning CT, and can be considered in the direct integration of PET-CT to the treatment planning process. Local recurrences occur within the PTVPET-CT, suggesting that this is a suitable target for dose escalation strategies. PMID- 27266820 TI - Administrative database code accuracy did not vary notably with changes in disease prevalence. AB - OBJECTIVES: Previous mathematical analyses of diagnostic tests based on the categorization of a continuous measure have found that test sensitivity and specificity varies significantly by disease prevalence. This study determined if the accuracy of diagnostic codes varied by disease prevalence. STUDY DESIGN AND SETTING: We used data from two previous studies in which the true status of renal disease and primary subarachnoid hemorrhage, respectively, had been determined. In multiple stratified random samples from the two previous studies having varying disease prevalence, we measured the accuracy of diagnostic codes for each disease using sensitivity, specificity, and positive and negative predictive value. RESULTS: Diagnostic code sensitivity and specificity did not change notably within clinically sensible disease prevalence. In contrast, positive and negative predictive values changed significantly with disease prevalence. CONCLUSION: Disease prevalence had no important influence on the sensitivity and specificity of diagnostic codes in administrative databases. PMID- 27266821 TI - Epicardial and paracardial adipose tissue volume and attenuation - Association with high-risk coronary plaque on computed tomographic angiography in the ROMICAT II trial. AB - BACKGROUND AND AIMS: To determine whether epicardial (EAT) and paracardial adipose tissue (PAT) volume and attenuation are associated with high-risk coronary plaque features. METHODS: In subjects with suspected acute coronary syndrome (ACS) enrolled in the ROMICAT II trial, EAT and PAT volumes indexed to body surface area (BSA) and attenuation were measured on non-contrast coronary artery calcium score (CACS) CT. High-risk plaque features (napkin-ring sign, positive remodeling, low density plaque, spotty calcium) and stenosis were assessed on coronary CT angiography (CTA). The association of EAT and PAT volume and attenuation with high-risk plaque and whether this was independent of clinical risk assessment, CACS and significant coronary artery disease (CAD) was determined. RESULTS: Of 467 (mean 54 +/- 8 yrs, 53% male) with CACS and CTA, 167 (36%) had high-risk plaque features. Those with high-risk plaque had significantly higher indexed EAT (median 59 (Q1-Q3:45-75) cc/m(2) vs. 49 (35-65) cc/m(2), p < 0.001) and PAT volume (median:51 (36-73) cc/m(2) vs. 33 (22-52) cc/m(2), p < 0.001). Higher indexed EAT volume was associated with high-risk plaque [univariate OR 1.02 (95%-CI:1.01-1.03) per cc/m(2) of EAT, p < 0.001], which remained significant [univariate OR 1.04 (95%-CI:1.00-1.08) per cc/m(2) of EAT, p = 0.040] after adjustment for risk factors, CACS, and stenosis >=50%. Higher indexed PAT volume was associated with high-risk plaque in univariate analysis [OR 1.02 (1.01-1.03) per cc/m(2) of PAT, p < 0.001], though this was not significant in multivariate analysis. At a threshold of >62.3 cc/m(2), EAT volume was associated with high-risk plaque [univariate OR 2.50 (95%-CI:1.69-3.72), p < 0.001)], which remained significant [OR 1.83 (95%-CI:1.10-3.05), p = 0.020] after adjustment. Subjects with high-risk plaque had lower mean attenuation EAT (-88.1 vs. -86.9 HU, p = 0.008) and PAT (-106 vs. -103 HU, p < 0.001), though this was not significant in multivariable analysis. CONCLUSIONS: Greater volumes of EAT are associated with high-risk plaque independent of risk factors, CACS and obstructive CAD. This observation supports possible local influence of EAT on development of high-risk coronary plaque. PMID- 27266822 TI - Serotonin and norepinephrine reuptake inhibitors antidepressant use is related to lower baroreflex sensitivity independently of the severity of depressive symptoms. A community-study of 9213 participants from the Paris Prospective Study III. AB - BACKGROUND AND AIMS: We assess the respective relationship of high depressive symptoms and antidepressant use (ATD) with baroreflex sensitivity (BRS) in subjects from the community who enrolled the Paris Prospective Study III. METHODS: Recruitment took place in a large health preventive centre in Paris (France), between May 2008 and June 2012. BRS was investigated by spectral analysis of the spontaneous carotid distension rate and RR intervals using non invasive high-resolution ultrasound carotid-echotracking. A total score >=7 on a 13-item standardized questionnaire defined the presence of high depressive symptoms. Information on ATD use was obtained on a face-to-face interview with a medical doctor who checked the most recent medical prescriptions and/or medical package. RESULTS: There were 9213 participants aged 50-75 years (38.6% of women), including 5.6% with high-depressive symptoms and 5.2% on ATD. High depressive symptoms were not associated with low BRS (below the median) even in unadjusted logistic regression analysis (OR = 1.09; 95%CI: 0.91-1.30). Instead, ATD use was related to low BRS in multivariate logistic regression analysis (OR = 1.27; 95% CI: 1.04-1.54). This association remains after adjusting for and matching on propensity score of receiving ATD. A specific association with serotonin and norepinephrine reuptake inhibitors was observed (OR = 1.94; 95% CI: 1.16-3.22). CONCLUSIONS: ATD use and serotonin and norepinephrine reuptake inhibitors in particular, but not high depressive symptoms, is associated with low BRS. If confirmed, these results may bring novel insights into the mechanisms linking depressive symptoms and/or ATD use with cardiovascular disease onset. PMID- 27266823 TI - Carotid endothelial shear stress reduction with aging is associated with plaque development in twelve years. AB - BACKGROUND AND AIMS: Atherosclerosis is associated with clinical, biochemical and haemodynamic risk factors. In a group of subjects studied twelve years apart, we evaluated carotid plaque development in relation to baseline and to changes at follow-up in common carotid haemodynamic profile. METHODS: Forty-eight participants were recruited to a cardiovascular disease prevention programme. Atherosclerotic plaques were evaluated and scored by echography. Endothelial shear stress, circumferential wall tension, and Peterson's elastic modulus as an index of arterial stiffness, were computed by echo-Doppler, along with blood viscosity data. Binary logistic regression analyses were used to test the association among the development of atherosclerosis, cardiovascular risk factors and haemodynamic variations. Analyses were also performed on participants who presented at the follow-up with carotid haemodynamic variations in the left or right common carotid only. RESULTS: Participants (69% male) were aged 64.5 +/- 9.7 years at follow-up. Peak and mean endothelial shear stress was significantly lower at follow-up as previously reported; circumferential wall tension and arterial stiffness were significantly higher. Carotid plaque scores increased after 12 years (0.39 +/- 0.72 vs. 0.67 +/- 0.86, p < 0.01). Of the 96 common carotids analysed, shear stress reduction with aging was an independent predictor of carotid atherosclerosis (B = -0.063; odds ratio = 0.94; p = 0.01). Out of 48 participants, 21 (44%) showed shear stress reduction with aging in only one side of the body and, on this side, the plaque score increased (0.52 +/- 0.98 vs. 0.90 +/- 0.94, p < 0.05), remaining unchanged in the contralateral carotid tree. CONCLUSIONS: Aging-related shear stress reduction is an independent predictor of atherosclerosis development. PMID- 27266824 TI - A non-hypocholesterolemic atorvastatin treatment improves vessel elasticity by acting on elastin composition in WHHL rabbits. AB - BACKGROUND AND AIMS: Statins are prescribed for their preventative effects within atherosclerosis development. To our knowledge, no study focusing on very low-dose (non-hypolipidemic effect) and long-term atorvastatin treatment in vivo was available. Our aim was to assess the effect of such atorvastatin treatment on the mechanical and functional characteristics of arteries in the context of primary prevention. METHODS: An atorvastatin treatment (2.5 mg/kg/day) was tested against controls on 34 male 3 to 12 month-old WHHL rabbits. No effect on total cholesterol, triglycerides, HDL or LDL was observed. The arterial stiffness was evaluated on vigil animals by pulse wave velocity (PWV) measurement. Then, in vitro measurements were made to evaluate (1) the endothelial and vascular smooth muscle function, (2) the elasticity of the arterial wall and (3) the composition in collagen and elastin in the aorta. RESULTS: The PWV increasing observed with age in control group was canceled by treatment, creating a significance difference between groups at 12 months (5.17 +/- 0.50 vs 2.14 +/- 0.34 m s(-1) in control and treated groups respectively). Vasoreactivity modifications can't explain this result but maintain of elasticity with treatment in large arteries was confirm by a static tensile test. A first possible explanation is the change of wall composition with treatment, validated by the percentage of elastin at 12 months, 4.4% lower in the control group compared to the treated group (p < 0.05). CONCLUSIONS: This study shows that a non-hypocholesterolemic statin treatment could improve vessel elasticity in the atherosclerotic WHHL model. The great novelty of this work is the vessel wall composition changing associated. This first approach in animal opens the reflection on the use of these low doses in humans. This could be interesting in the context of arterial stiffening with aging, non-hyperlipidemic atherosclerosis or with cholesterol reduce by another therapy or lifestyle modification. PMID- 27266825 TI - Combined Medical and Surgical Approach Improves Healing of Septic Perianal Crohn's Disease. AB - BACKGROUND: Septic perianal Crohn's disease (SPCD) is a treatment challenge in spite of tumor necrosis factor antagonists (anti-TNF). Our aim was to define the success of SPCD management with a combined medical and surgical approach and to identify clinical and genetic factors predictive of healing. STUDY DESIGN: A retrospective chart review of patients with SPCD treated at the Penn State Milton S Hershey Medical Center was done. Primary end point was complete healing (ie normal clinical exam and no pain for at least 6 months). Genetic analysis of 185 single nucleotide polymorphisms associated with Crohn's disease was performed in 78 patients. RESULTS: One hundred and thirty-five episodes of SPCD were identified in 114 patients with a mean follow-up of 77 +/- 7.4 months. Overall, 80 of 135 episodes healed (59.3%) and did not differ between those receiving anti TNF and not (60.4% vs 56.8%). There appeared to be a consistent improved heal rate in each subcategory of surgically managed patients that received anti-TNF. Female sex was significantly predictive of healing in only those receiving anti TNF agents (63.6% vs 25.0%; p = 0.0005). Twenty-two (19.3%) patients ultimately received a permanent diversion with either a total proctocolectomy or completion proctectomy. Multivariate analysis suggested several single nucleotide polymorphisms in Crohn's disease-associated genes to be possibly associated with healing, but lost significance after Bonferroni correction. CONCLUSIONS: Overall, there is an approximate 60% rate of healing SPCD using a combined medical and surgical approach. About 20% of SPCD patients will require a permanent stoma. There were no clear genetic predictors of healing SPCD. PMID- 27266826 TI - Emergency presentation of cystic lymphangioma of the colon: A case report and literature review. AB - INTRODUCTION: Colonic lymphangioma is an unusual benign malformation. The clinical presentation of lymphangiomas vary from incidental discovery on imaging to presenting with acute abdomen. PRESENTATION OF CASE: We present the case of a 73-year-old male, undergoing surgery due to acute abdomen associated with severe anemia, in whose case a lymphangioma of the cecum was recognised only in the postoperative histopathological examination. DISCUSSION: The management of colonic lymphangioma depends on the individual situation; close surveillance or endoscopic therapy may be appropriate for asymptomatic lesions smaller than 2.5cm in diameter. Surgical intervention can be considered for larger lesions or in patients who develop complications. CONCLUSION: The interest in our case lies in the relatively rare diagnosis of colon lymphangioma and how the cardinal sign was anemia, which may be due to the serosanguineous cystic contents of lymphangiomatosis from the internal bleeding and can cause fatal complications that require emergency surgery. PMID- 27266827 TI - A case report of successful removal of multiples sewing needles in the gastrointestinal tract and pancreas using intraoperative C-arm fluoroscopy. AB - BACKGROUND: Most ingested foreign bodies pass uneventfully through the digestive tract without any major disturbances. OBJECTIVES: We reports a rare case of successful localization and surgical removal of needles in the gastrointestinal tract using C-arm fluoroscopy intraoperatively. CASE REPORT: A 46year old female, a non-hospitalized psychiatric patient, presented with acute abdominal pain. Imaging showed 16 needles all over the digestive tract. C arm fluoroscopy was used to successfully localize and remove all of the needles intraoperatively. One needle was withdrawn from the pancreas manually without pancreatic resection. DISCUSSION: It is estimated that up to 10-20% cases require endoscopic removal and 1% cases with the presence of obstruction or perforation necessitate surgical interventions [1-4] (Hsieh et al., 2005; Anderson and Dean, 2011; Cheng and Tam, 1999; Ricci et al., 2014). Migration to the pancreas extremely rare [5,6] (Toyonaga et al., 2001; Yasuda et al., 2010). Timely diagnosis can be difficult [7] (Tsui and Mossey, 1997). CT scan is a modality of choice to preoperatively locate the foreign body [8] (Takada et al., 2000). We herein successfully localized and removed 15 needles using C-arm fluoroscopy intraoperatively. It is extremely useful to accurately detect radiopaque foreign bodies. On the basic of findings on CT, treatment of choice such as endoscopic removal or surgical intervention may be attempted. CONCLUSIONS: CT scan is a modality of choice to preoperatively locate the foreign body. Sharp-pointed objects should be removed even if the patient is asymptomatic as the increased mortality and the risk of related complications. Intraoperative C-arm fluoroscopy is a feasible, cost effective modality with real-time image to accurately detect multiple radiopaque objects especially when they are disseminating throughout the digestive tract. PMID- 27266828 TI - Appendiceal perforation, necrotizing groin infection and spermatic cord necrosis in a case of Amyand's hernia. AB - INTRODUCTION: Inguinal hernias containing the appendix are described as Amyand's hernias. The surgical approach to these types of hernias is dependent on the type present and associated intra-operative findings. PRESENTATION OF CASE: We present a case of complicated type IV Amyand's hernia, which was managed though combined abdominal and inguinal approach. Though the patient had a prolonged post operative course due to pulmonary embolism, he progressed to full recovery. DISCUSSION: The different grades of Amyand's hernia are repaired in varying ways, including laparoscopic and open approaches with or without mesh. The type of repair must be tailored to the patient and disease process. CONCLUSION: Primary repair of a perforated Amyand's hernia provides adequate strength with decreased risk of infection due to synthetic material. PMID- 27266829 TI - Bilateral periprosthetic tibial stress fracture after total knee arthroplasty: A case report. AB - INTRODUCTION: Periprosthetic fractures around the knee after total knee arthroplasty can be seen in the femur, tibia and patella. The tibial fractures are rare cases. Our case with bilateral tibial stress fracture developed after total knee arthroplasty (TKA) is the first of its kind in the literature. PRESENTATION OF CASE: 75-year-old male patient with bilateral knee osteoarthritis had not benefited from conservative treatment methods previously applied. Left TKA was applied. In the second month postoperatively, periprosthetic tibial fracture was identified and osteosynthesis was implemented with locked tibia proximal plate-screw. Bone union in 12 weeks was observed in his follow-ups. After 15 months of his first operation, TKA was applied to the right knee. Postoperatively in the second month, as in the first operation, periprosthetic tibial fracture was detected. Osteosynthesis with locking plate-screw was applied and union in 12 weeks was observed in his follow-up. He was seen mobilized independently and without support in the last control of the case made in the 24th month after the second operation. DISCUSSION: The number of TKA applications is expected to increase in the future. The incidence of periprosthetic fractures should also be expected to increase in these cases. Periprosthetic tibial fractures after TKA are rarely seen. The treatment of periprosthetic fractures around the knee after TKA can be difficult. CONCLUSION: In the case of persistent pain in the upper end of the tibia after the surgery, stress fracture should be considered. PMID- 27266831 TI - Primary adult midgut volvulus mimicking acute appendicitis: A case report and review of the literature. AB - INTRODUCTION: Adult midgut volvulus is a rare surgical disease but remains an important cause of small bowel obstruction. It is most commonly secondary to postoperative adhesions. Primary cases may be due to congenital malformations. PRESENTATION OF CASE: We report the case of an adult primary midgut volvulus in a 35-year-old Chinese male. Based on the clinical presentation and investigations, the patient was presumed to have acute appendicitis. An open appendectomy was performed. During the operation, the appendix appeared normal. Instead a jejunal volvulus was found secondary to extensive adhesions. DISCUSSION: The epidemiology, embryology and etiology of jejunal volvulus are highlighted. Clinical presentation includes acute colicky abdominal pain usually in the peri umbilical or epigastric regions, with possible signs of small bowel obstruction. Radiologic diagnosis is confirmed with the ultrasonic 'whirpool' sign or via computed tomography (CT) scan. Early surgical intervention is necessary to avert bowel ischemia in the presence of a closed loop obstruction. CONCLUSION: While rare, adult midgut volvulus has the potential for morbidity and mortality if not diagnosed early with intestinal ischaemia and related sequlae. Clinicians should consider this and if in doubt, perform an early contrast CT scan. PMID- 27266830 TI - Pyomyoma after abortion: Uterus conserving surgery is possible to maintain fertility. Case report. AB - INTRODUCTION: Pyomyoma is a rare complication associated with high rates of morbidity and mortality. PRESENTATION OF CASE: We report the case of a 28-year old nulligravida patient presenting pyomyoma following a spontaneous abortion at fourteen weeks and four days. Fourteen days following spontaneous miscarriage she was referred to the hospital with abdominal pain and fever. An antibiotic treatment was initiated. However, after ten days, the patient's condition deteriorated and a decision for an emergency laparotomy made. The pyomyoma was successfully resected and the patient's postoperative recovery was uneventful. A new pregnancy was confirmed two years later. DISCUSSION: The diagnosis of pyomyoma can be difficult but surgical treatment is often indicated. Performing a prompt myomectomy avoids the need for hysterectomy, preserving future fertility. CONCLUSION: Pregnancy is possible following uterine sparing treatment of pyomyoma. PMID- 27266832 TI - Long-term progress of six cases of malignant peripheral nerve sheath tumors of the mediastinum that underwent surgical treatment: Case report series. AB - INTRODUCTION: Malignant Peripheral Nerve Sheath Tumor is a rare type of soft tissue malignant tumor that occurs in only 5% of cases. It tends to occur in the arms and legs and trunk of the body, with mediastinal occurrence in only a few cases. Among mediastinal tumors, only 18.8% occur primarily in the nerves, and of these, only 10.3% are malignant, with very few reports indicating the long-term progress of patients with MPNST of the mediastinum. CASE PRESENTATION: We studied six cases of mediastinal primary malignant peripheral nerve sheath tumors in which surgery was carried out at this Center between 1977 and 2000. Four of the cases were men and two were women. The period of observation was between 14 and 277 months and the median follow-up time was 119.5 months. The tumors were contained in a membrane and completely excisable in three cases, with the patient demonstrating long-term survival with no recurrence in each case. The remaining three cases were not completely excisable due to invasion into the aorta. In two cases, the patients were treated post-surgically with chemotherapy; however, in all three cases the patient died as a result of the original condition. DISCUSSION AND CONCLUSIONS: Nerve sheath tumors localized within the membrane offer good long-term prognosis even if malignant. Furthermore, long-term survival is possible even if the tumor has invaded neighboring organs, provided it can be completely excised. In cases where complete excision is difficult, a multidisciplinary approach including radiotherapy and anti-cancer drug treatment may contribute to improved prognosis but this is a subject that requires further study. PMID- 27266833 TI - Ln2Ga[B3O6(OH)]2[B7O9(OH)2](CH3CO2)2 (Ln = Y, Sm, Eu, Gd, Dy): A Series of Lanthanide Galloborates Decorated by Acetate Anions. AB - The first examples of mixed-anion lanthanide galloborates, namely, Ln2Ga[B3O6(OH)]2[B7O9(OH)2](CH3CO2)2 [Ln = Y (1), Sm (2), Eu (3), Gd (4), Dy (5)], have been obtained through hydrothermal synthesis. The title compounds are isomorphic and belong to monoclinic space group C2/c (No. 15). Their structures possess [B7O13(OH)2] borate layers further bridged with [B3O7] clusters to give a three-dimensional (3D) borate framework displaying two types of rhombus-like B14O14 14-membered-ring (14-MR) channels along the b axis. The Ga(3+) ions are octahedrally coordinated and located at one end of the B14O14 14-MR channels, forming small tunnels of B7Ga 8-MRs, which are filled by the Ln(III) ions. The Ln ions and Ga cations are further held together by bridging acetate anions. It is worth noting that in these compounds there are two different types of borate clusters and two types of anions that are uncommon in the borates reported. Luminescent studies revealed the characteristic emission bands of Ln ions for compounds 2-5, and the luminescent lifetimes are 3.6, 0.86, and 3.05 ns for compounds 2, 3, and 5, respectively. Magnetic measurements suggest that there are antiferromagnetic interactions between magnetic centers for compounds 2-5. PMID- 27266834 TI - Tandem Rh(III)-Catalyzed C-H Amination/Annulation Reactions: Synthesis of Indoloquinoline Derivatives in Water. AB - An efficient Rh(III)-catalyzed synthetic method for indoloquinoline derivatives from readily available indoles and isoxazoles was developed. This annulation procedure undergoes tandem C-H activation, cyclization, and condensation steps. In this domino cyclization reaction, water is an efficient solvent. A catalytically competent five-membered rhodacycle has been isolated and characterized, thus revealing a key intermediate in the catalytic cycle. PMID- 27266835 TI - Dual resistance to lambda-cyhalothrin and dicrotophos in Hippodamia convergens (Coleoptera: Coccinellidae). AB - Insecticide resistance is usually associated with pests, but may also evolve in natural enemies. In this study, adult beetles of three distinct North American populations of Hippodamia convergens Guerin-Meneville, and the progeny of reciprocal crosses between the resistant and most susceptible population, were treated topically with varying concentrations of lambda-cyhalothrin and dicrotophos. In addition, the LD50s of both insecticides were applied in combination to resistant individuals. The developmental and reproductive performance of each population was assessed in the absence of insecticide exposure to compare baseline fitness. California and Kansas populations were susceptible to both materials, whereas Georgia (GA) beetles exhibited a resistance ratio (RR50) of 158 to lambda-cyhalothrin and 530 to dicrotophos. Inheritance of lambda-cyhalothrin resistance was X-linked, whereas inheritance of dicrotophos resistance was autosomal. Mortality of resistant beetles treated with a mixture of LD50s of both materials was twice that of those treated with lambda cyhalothrin alone, but not significantly different from those receiving dicrotophos alone. Life history parameters were largely similar among populations, except that Georgia beetles had higher egg fertility relative to susceptible populations. We conclude that the high levels of resistance to lambda cyhalothrin and dicrotophos in Georgia beetles reflect heavy loads of these insecticides in local environments, most likely the large acreage under intensive cotton cultivation. PMID- 27266836 TI - Environmental occurrence, analysis and human exposure to the flame retardant tetrabromobisphenol-A (TBBP-A)-A review. AB - TBBP-A is a high production volume chemical applied widely as a flame retardant in printed circuit boards. Recent studies have raised concern over potential harmful implications of TBBP-A exposure in human and wildlife, leading to its classification under group 2A "Probably carcinogenic to humans" by the International Agency for Research on Cancer. This article provides a comprehensive review of the available literature on TBBP-A analysis, environmental levels and human exposure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been identified as the method of choice for robust, accurate and sensitive analysis of TBBP-A in different matrices. TBBP-A has been detected in almost all environmental compartments all over the world, rendering it a ubiquitous contaminant. Human exposure studies revealed dust ingestion and diet as the major pathways of TBBP-A exposure in the general population. Toddlers are likely to be more exposed than adults via accidental indoor dust ingestion. Moreover, exposure to TBBP-A may occur prenatally and via breast milk. There are no current restrictions on the production of TBBP-A in the EU or worldwide. However, more research is required to characterise human exposure to TBBP-A in and around production facilities, as well as in e-waste recycling regions. PMID- 27266837 TI - Nuclear compartmentalization of DNA repair. AB - The continuous threats on genome integrity by endogenous and exogenous sources have rendered cells competent to overcome these challenges by activating DNA repair pathways. A complex network of proteins and their modifications participate in orchestrated signaling cascades, which are induced in response to DNA damage and may determine the choice of repair pathway. In this review, we summarize recent findings in the field of DNA Double Strand Break repair with regard to the positioning of the break in the highly compartmentalized nucleus. We aim to highlight the importance of chromatin state along with the nuclear position of the DNA lesions on the choice of DNA repair pathway and maintenance of genome integrity. PMID- 27266838 TI - Tension pneumopericardium in blunt thoracic trauma. AB - INTRODUCTION: Pneumopericardium, defined as the presence of gas in the pericardial sac, is a rare condition caused mostly by trauma. Tension pneumopericardium is a cause of hemodynamic instability; hence, it consists in a life-threatening situation and should be regarded in blunt chest trauma. CASE REPORT: A 51-year-old male was victim of a 4m fall and burial. He was stable upon admission and presented a simple pneumopericardium and pneumomediastinum on CT. While being submitted to an upper digestive endoscopy he presented respiratory failure and had to be intubated, suddenly evolving to shock. He was promptly referred to the operating room; a pericardial window confirmed tension pneumopericardium and immediately hemodynamic stability was restored. A pericardial drain was placed and kept for 15days. He was discharged at the 18th day post-trauma after a satisfactory recovery at the trauma ICU. DISCUSSION: Blunt thoracic trauma causes pneumopericardium by various mechanisms. Tension pneumopericardium is a possible outcome, probably related to positive-pressure ventilation. It leads to hemodynamic instability and requires immediate decompression and placement of a pericardial drain. PMID- 27266839 TI - Right hemicolectomy for mesenteric phlebosclerosis potentially caused by long term use of herbal medicine: A case report and literature review. AB - INTRODUCTION: Mesenteric phlebosclerosis is a rare ischemic disease affecting the colon. Systemic disease and herbal medicine have been pointed out as possible causes, and the disease is characterized by calcifications involved the mesocolic veins. Patients who do not respond to conservative therapy require surgical treatment. In surgical intervention, an adequate extent of colonic resection is important. PRESENTATION OF CASE: We present a case of an 87-year-old woman with mesenteric phlebosclerosis who had consumed herbal medicine for 40 years. She suffered from ileus caused by mesenteric phlebosclerosis, and the symptoms did not improve with conservative therapy. Right hemicolectomy was performed since the disease was localized in the right colon. Long-term use of herbal medicine was considered the potential cause of mesenteric phlebosclerosis. The postoperative course was mostly uneventful. The patient stopped using herbal medicine and had no signs of recurrence 2 years after surgery. DISCUSSION AND CONCLUSION: The greatest concern in surgery for mesenteric phleboscrerosis is to detect the affected area, which should be removed. Characteristic findings in computed tomography and intraoperative findings can help to determine the optimal extent of colonic resection. Mesenteric phlebosclerosis caused by herbal medicines occurs as localized disease in the right colon compared with mesenteric phlebosclerosis caused by other pathogenesis. Limited colonic resection is usually indicated for mesenteric phlebosclerosis caused by herbal medicine. PMID- 27266840 TI - Laceration of a branch of the profunda femoris artery caused by a spike of the displaced lesser trochanter in an inter-trochanteric femoral fracture. A case report. AB - INTRODUCTION: Injury of femoral vessels is an extremely rare complication in intertrochanteric femoral fractures. In most cases reported, the vascular lesion involves the superficial femoral artery, whereas in very few cases does it involve the profunda femoris artery. PRESENTATION OF CASE: We report a case of acute bleeding due to laceration of a perforating branch of the profunda femoris artery caused by a sharp fragment of the displaced lesser trochanter in an intertrochanteric femoral fracture; the lesion was treated by transcatheter embolization. DISCUSSION: The arterial injury may be iatrogenic, occurring during intramedullary internal fixation, or less frequently, the injury may be due to the fracture itself, caused by a sharp bone fragment that damages the profunda femoris artery or one of its perforating branches. CONCLUSION: We believe that intertrochanteric femoral fractures with avulsed lesser trochanter are at risk for femoral vessel injuries caused by the displaced bone spike, and we advise meticulous clinical and laboratory monitoring pre- and post-operatively to prevent serious complications. PMID- 27266841 TI - A reexamination of poneratoxin from the venom of the bullet ant Paraponera clavata. AB - In 1991, Piek et al. [45] described a voltage-gated sodium channel (VGSC) modifier from "bullet ant" (Paraponera clavata) venom they called poneratoxin (PoTx). Using UV chromatography and Edman degradation they showed two "identical peptides" of 25 residues. We reinvestigated PoTx using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-TMS). De novo sequencing showed the two peptides were actually structurally different peptides: the originally described PoTx and a glycyl pro-peptide (glycyl-PoTx) that lacks C-terminus amidation. We examined P. clavata venom from different geographical locations and discovered two additional PoTx analogs: an A23E substitution analog and a D22N; A23V substitutions analog. We tested PoTx and these three natural analogs on the mammalian sensory voltage-gated sodium channel, Nav1.7, using whole cell voltage clamp. PoTx and each analog induced slowly activating currents in response to small depolarizing steps and sustained currents due to blockade of channel inactivation, similar to that described previously in skeletal muscle [19]. Glycyl-PoTx had the same potency and efficacy as PoTx. A23E PoTx, with a decrease in both C-terminal net positive charge and hydrophobicity, had an eight-fold reduction in potency compared to PoTx. In contrast, the D22N; A23V PoTx, with an increase in both C-terminal net positive charge and hydrophobicity, had a nearly five-fold increase in potency compared to PoTx. We found that changes in PoTx C terminus caused a significant change in PoTx potency. PMID- 27266842 TI - Hyperoxia disrupts the intestinal barrier in newborn rats. AB - Animal studies have demonstrated that neonatal hyperoxia injures the distal small intestine. This study aimed to determine the effects of neonatal hyperoxia exposure on the intestinal morphology and intestinal barrier integrity in newborn rats. Sprague-Dawley rat pups were exposed to either ambient air or hyperoxia. The ambient air and normobaric hyperoxia groups were maintained in room air and 85% O2 for 2weeks, respectively. The rats were euthanized on Postnatal Day 14, and the terminal ileum was collected for histological analyses and oxidative stress measurements. The generation of reactive oxygen species was evaluated by measuring the production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). The expression and localization of epithelial injury markers [intestinal fatty acid binding protein (I-FABP)] and intestinal barrier proteins [occludin and zonula occludens (ZO)-1] were analyzed through immunofluorescence staining and western blotting. The body weight at birth was comparable between the two groups. On Postnatal Day 14, the rats in the hyperoxia group exhibited significantly lower body weight, a higher serum interleukin-6 level, a higher intestinal injury score, higher 8-OHdG and I-FABP expression, and lower occludin and ZO-1 protein expression than did those in the ambient air group. Hyperoxia exposure injured the distal small intestine and disrupted the intestinal barrier in newborn rats. This may be attributable to oxidative stress during the postnatal period. PMID- 27266843 TI - The Hexadehydro-Diels-Alder Cycloisomerization Reaction Proceeds by a Stepwise Mechanism. AB - We report here experiments showing that the hexadehydro-Diels-Alder (HDDA) cycloisomerization reaction proceeds in a stepwise manner-i.e., via a diradical intermediate. Judicious use of substituent effects was decisive. We prepared (i) a series of triyne HDDA substrates that differed only in the R group present on the remote terminus of the diynophilic alkyne and (ii) an analogous series of dienophilic alkynes (n-C7H15COC=CR) for use in classical Diels-Alder (DA) reactions (with 1,3-cyclopentadiene). The R groups were CF3, CHO, COMe/Et, CO2Me, CONMe2/Et2, H, and 1-propynyl. The relative rates of both the HDDA cyclization reactions and the simple DA cycloadditions were measured. The reactivity trends revealed a dramatic difference in the behaviors of the CF3 (slowest HDDA and nearly fastest DA) and 1-propynyl (fastest HDDA and slowest DA) containing members of each series. These differences can be explained by invoking radical stabilizing energies rather than electron-withdrawing effects as the dominating feature of the HDDA reaction. PMID- 27266844 TI - Quantifying spatiotemporal heterogeneity of MERS-CoV transmission in the Middle East region: A combined modelling approach. AB - MERS coronavirus cases notified in the Middle East region since the identification of the virus in 2012 have displayed variations in time and across geography. Through a combined modelling approach, we estimate the rates of generation of cases along the zoonotic and human-to-human transmission routes and assess their spatiotemporal heterogeneity. We consider all cases notified to WHO from March 2012 to mid-September 2014. We use a stochastic modelling of the time series of case incidence in the Middle East region to estimate time- and space dependent zoonotic and human-to-human transmission parameters. The model also accounts for possible lack of identification of secondary transmissions among notified cases. This approach is combined with the analysis of imported cases out of the region to assess the rate of underreporting of cases. Out of a total of 32 possible models, based on different parameterisation and scenario considered, the best-fit model is characterised by a large heterogeneity in time and across space for both zoonotic and human-to-human transmission. The variation in time that occurred during Spring 2014 led to a 17-fold and 3-fold increase in the two transmissions, respectively, bringing the reproductive rate to values above 1 during that period for all regions under study. The model suggests that 75% of MERS-CoV cases are secondary cases (human-to-human transmission), which is substantially higher than the 34% of reported cases with an epidemiological link to another case. Overall, estimated reporting rate is 0.26. Our findings show a higher level of spatial heterogeneity in zoonotic transmission compared to human to-human, highlighting the strong environmental component of the epidemic. Since sporadic introductions are predicted to be a small proportion of notified cases and are responsible for triggering secondary transmissions, a more comprehensive understanding of zoonotic source and path of transmission could be critical to limit the epidemic spread. PMID- 27266846 TI - EpiJSON: A unified data-format for epidemiology. AB - Epidemiology relies on data but the divergent ways data are recorded and transferred, both within and between outbreaks, and the expanding range of data types are creating an increasingly complex problem for the discipline. There is a need for a consistent, interpretable and precise way to transfer data while maintaining its fidelity. We introduce 'EpiJSON', a new, flexible, and standards compliant format for the interchange of epidemiological data using JavaScript Object Notation. This format is designed to enable the widest range of epidemiological data to be unambiguously held and transferred between people, software and institutions. In this paper, we provide a full description of the format and a discussion of the design decisions made. We introduce a schema enabling automatic checks of the validity of data stored as EpiJSON, which can serve as a basis for the development of additional tools. In addition, we also present the R package 'repijson' which provides conversion tools between this format, line-list data and pre-existing analysis tools. An example is given to illustrate how EpiJSON can be used to store line list data. EpiJSON, designed around modern standards for interchange of information on the internet, is simple to implement, read and check. As such, it provides an ideal new standard for epidemiological, and other, data transfer to the fast-growing open-source platform for the analysis of disease outbreaks. PMID- 27266845 TI - Decision-making for foot-and-mouth disease control: Objectives matter. AB - Formal decision-analytic methods can be used to frame disease control problems, the first step of which is to define a clear and specific objective. We demonstrate the imperative of framing clearly-defined management objectives in finding optimal control actions for control of disease outbreaks. We illustrate an analysis that can be applied rapidly at the start of an outbreak when there are multiple stakeholders involved with potentially multiple objectives, and when there are also multiple disease models upon which to compare control actions. The output of our analysis frames subsequent discourse between policy-makers, modellers and other stakeholders, by highlighting areas of discord among different management objectives and also among different models used in the analysis. We illustrate this approach in the context of a hypothetical foot-and mouth disease (FMD) outbreak in Cumbria, UK using outputs from five rigorously studied simulation models of FMD spread. We present both relative rankings and relative performance of controls within each model and across a range of objectives. Results illustrate how control actions change across both the base metric used to measure management success and across the statistic used to rank control actions according to said metric. This work represents a first step towards reconciling the extensive modelling work on disease control problems with frameworks for structured decision making. PMID- 27266847 TI - A generalized-growth model to characterize the early ascending phase of infectious disease outbreaks. AB - BACKGROUND: A better characterization of the early growth dynamics of an epidemic is needed to dissect the important drivers of disease transmission, refine existing transmission models, and improve disease forecasts. MATERIALS AND METHODS: We introduce a 2-parameter generalized-growth model to characterize the ascending phase of an outbreak and capture epidemic profiles ranging from sub exponential to exponential growth. We test the model against empirical outbreak data representing a variety of viral pathogens in historic and contemporary populations, and provide simulations highlighting the importance of sub exponential growth for forecasting purposes. RESULTS: We applied the generalized growth model to 20 infectious disease outbreaks representing a range of transmission routes. We uncovered epidemic profiles ranging from very slow growth (p=0.14 for the Ebola outbreak in Bomi, Liberia (2014)) to near exponential (p>0.9 for the smallpox outbreak in Khulna (1972), and the 1918 pandemic influenza in San Francisco). The foot-and-mouth disease outbreak in Uruguay displayed a profile of slower growth while the growth pattern of the HIV/AIDS epidemic in Japan was approximately linear. The West African Ebola epidemic provided a unique opportunity to explore how growth profiles vary by geography; analysis of the largest district-level outbreaks revealed substantial growth variations (mean p=0.59, range: 0.14-0.97). The districts of Margibi in Liberia and Bombali and Bo in Sierra Leone had near-exponential growth, while the districts of Bomi in Liberia and Kenema in Sierra Leone displayed near constant incidences. CONCLUSIONS: Our findings reveal significant variation in epidemic growth patterns across different infectious disease outbreaks and highlights that sub-exponential growth is a common phenomenon, especially for pathogens that are not airborne. Sub-exponential growth profiles may result from heterogeneity in contact structures or risk groups, reactive behavior changes, or the early onset of interventions strategies, and consideration of "deceleration parameters" may be useful to refine existing mathematical transmission models and improve disease forecasts. PMID- 27266849 TI - A population's higher-risk sexual behaviour is associated with its average sexual behaviour-An ecological analysis of subpopulations in Ethiopia, Kenya, South Africa, Uganda and the United States. AB - BACKGROUND: Given the large variation in the prevalence of sexually transmitted infections between populations it is important to characterize how sexual vary between populations. In this paper we assess how the distribution of lifetime sexual partners varies between populations. We ask: do populations with higher mean lifetime sexual partners merely differ by virtue of the presence of a core group with increased number of partners or do the population distributions move as more coherent wholes? METHODS: We defined those in the top decile of lifetime sex partners in each country as constituting the higher-risk behaviour group (HRB). Spearman's correlation was used to evaluate the relationship between mean lifetime partners and prevalence of those in the HRB by ethnic group within Ethiopia, Kenya, South Africa, Uganda and the United States. In each case, data from nationally representative surveys were used. Two-sample Wilcoxon rank-sum were applied to test if there was a difference in the number of lifetime partners between the highest and lowest-risk subpopulations, separately for men and women. To account for autocorrelation, all analyses were conducted using means/medians excluding those in the HRB. A P-value of <0.05 was considered statistically significant. RESULTS: In each country, a positive correlation existed between subpopulations' mean lifetime partners and the prevalence of the HRB. Spearman's correlation varied from 0.20 to 0.99 for men and 0.74 to 1.0 for women. This association was statistically significant in 6 out of 10 comparisons. There was a statistically significant difference in the number of lifetime partners between the highest and lowest-risk ethnic groups in all countries except South Africa, where the difference was only significant for women. CONCLUSIONS: Our results suggest that sexual behaviours vary coherently between different populations. As such, sexually transmitted infection control efforts would benefit from including both targeted campaigns focusing on the HRB and population-strategies that seek to address factors responsible for high mean risk behaviour. PMID- 27266848 TI - Design and methods of a social network isolation study for reducing respiratory infection transmission: The eX-FLU cluster randomized trial. AB - BACKGROUND: Social networks are increasingly recognized as important points of intervention, yet relatively few intervention studies of respiratory infection transmission have utilized a network design. Here we describe the design, methods, and social network structure of a randomized intervention for isolating respiratory infection cases in a university setting over a 10-week period. METHODOLOGY/PRINCIPAL FINDINGS: 590 students in six residence halls enrolled in the eX-FLU study during a chain-referral recruitment process from September 2012 January 2013. Of these, 262 joined as "seed" participants, who nominated their social contacts to join the study, of which 328 "nominees" enrolled. Participants were cluster-randomized by 117 residence halls. Participants were asked to respond to weekly surveys on health behaviors, social interactions, and influenza like illness (ILI) symptoms. Participants were randomized to either a 3-Day dorm room isolation intervention or a control group (no isolation) upon illness onset. ILI cases reported on their isolation behavior during illness and provided throat and nasal swab specimens at onset, day-three, and day-six of illness. A subsample of individuals (N=103) participated in a sub-study using a novel smartphone application, iEpi, which collected sensor and contextually-dependent survey data on social interactions. Within the social network, participants were significantly positively assortative by intervention group, enrollment type, residence hall, iEpi participation, age, gender, race, and alcohol use (all P<0.002). CONCLUSIONS/SIGNIFICANCE: We identified a feasible study design for testing the impact of isolation from social networks in a university setting. These data provide an unparalleled opportunity to address questions about isolation and infection transmission, as well as insights into social networks and behaviors among college-aged students. Several important lessons were learned over the course of this project, including feasible isolation durations, the need for extensive organizational efforts, as well as the need for specialized programmers and server space for managing survey and smartphone data. PMID- 27266850 TI - Extension of Structure-Reactivity Correlations for the Hydrogen Abstraction Reaction to the Methyl Radical and Comparison to the Chlorine Atom, Bromine Atom, and Hydroxyl Radical. AB - Recently, we presented structure-reactivity correlations for the gas-phase rate constants for hydrogen abstraction from sp(3)-hybridized carbon by three electrophilic radicals (X(*) + HCR3 -> XH + (*)CR3; X = Cl(*), HO(*), and Br(*)); the reaction enthalpy effect was represented by the independent variable DeltarH and the "polar effect" by the independent variables F and R, the Hammett-Taft constants for field/inductive and resonance effects. Here we present a parallel treatment for the less electronegative CH3(*). In spite of a limited and scattered database, the resulting least-squares fit [log k437(CH3(*)) = 0.0251(DeltarH) + 0.96(SigmaF) - 0.56(SigmaR) - 19.15] was modestly successful and useful for initial predictions. As expected, the polar effect appears to be minor and its directionality, i.e., the "philicity" of CH3(*), may depend on the nature of the substituents. PMID- 27266851 TI - Cepharanthine and Piperine ameliorate diabetic nephropathy in rats: role of NF kappaB and NLRP3 inflammasome. AB - AIMS: Hyperglycemia leads to elevation of oxidative stress and proinflammatory cytokines which are the main causes of diabetic nephropathy (DN). NLRP3 inflammasome and thioredoxin-interacting protein (TXNIP) are recently assumed to participate in the development of DN. We aimed to investigate the effects of Cepharanthine (CEP), Piperine (Pip) and their combination in streptozotocin (STZ) induced DN focusing on their role to modulate NLRP3 and TXNIP induced inflammation. MAIN METHODS: Diabetic rats were treated with intraperitoneal (i.p.) injection of CEP (10mg/kg/day), Pip (30mg/kg/day) or their combination for 8weeks. Nuclear factor kappa B (NF-kappaB), tumor necrosis factor alpha (TNF alpha) and interleukin-1beta (IL-1beta) were assessed by ELISA technique. TXNIP and NLRP3 genes expressions were evaluated by real time-PCR. KEY FINDINGS: Diabetic rats showed significant increase in renal TXNIP and NLRP3 expression. CEP, Pip or their combination significantly decreased TXNIP and NLRP3 expression in diabetic kidneys. Hyperglycemia induced NF-kappaB activation leading to increased IL-1beta and TNF-alpha levels. CEP, Pip or their combination showed significant inhibition of NF-kappaB together with decreased IL-1beta and TNF alpha levels in diabetic rats. Also, diabetic rats showed significant decrease in creatinine clearance and increase in blood glucose, serum creatinine, blood urea nitrogen, malondialdehyde, proteinuria, and kidney weight to body Weight ratio. All of these changes were reversed by CEP, Pip or their combination. SIGNIFICANCE: The antioxidant and anti-inflammatory effects of CEP and Pip which were accompanied by inhibition of NF-kappaB and NLRP3 activation might be helpful mechanisms to halt the progression of DN. PMID- 27266852 TI - YouTube as a Potential Training Resource for Laparoscopic Fundoplication. AB - OBJECTIVE: To analyze the surgical proficiency and educational quality of YouTube videos demonstrating laparoscopic fundoplication (LF). DESIGN: In this cross sectional study, a search was performed on YouTube for videos demonstrating the LF procedure. The surgical and educational proficiency was evaluated using the objective component rating scale, the educational quality rating score, and total video quality score. Statistical significance was determined by analysis of variance, receiver operating characteristic curve, and odds ratio analysis. RESULTS: A total of 71 videos were included in the study; 28 (39.4%) videos were evaluated as good, 23 (32.4%) were moderate, and 20 (28.2%) were poor. Good-rated videos were significantly longer (good, 22.0 +/- 5.2min; moderate, 7.8 +/- 0.9min; poor, 8.5 +/- 1.0min; p = 0.007) and video duration was predictive of good quality (AUC, 0.672 +/- 0.067; 95% CI: 0.541-0.802; p = 0.015). For good quality, the cut-off video duration was 7:42 minute. This cut-off value had a sensitivity of 67.9%, a specificity of 60.5%, and an odds ratio of 3.23 (95% CI: 1.19-8.79; p = 0.022) in predicting good quality. Videos uploaded from industrial sources and with a higher views/days online ratio had a higher objective component rating scale and total video quality score. In contrast, the likes/dislikes ratio was not predictive of video quality. CONCLUSIONS: Many videos showing the LF procedure have been uploaded to YouTube with varying degrees of quality. A process for filtering LF videos with high surgical and educational quality is feasible by evaluating the video duration, uploading source, and the views/days online ratio. However, alternative videos platforms aimed at professionals should also be considered for educational purposes. PMID- 27266853 TI - Combining Diuretic Response and Hemoconcentration to Predict Rehospitalization After Admission for Acute Heart Failure. AB - BACKGROUND: Both diuretic response and hemoconcentration are indicators of decongestion and have individually been found to predict rehospitalization after admission for acute heart failure (HF). This study examines the value of combining diuretic response and hemoconcentration to better predict patients at low risk for rehospitalization after admission for acute HF. METHODS AND RESULTS: Diuretic response (defined as weight change per 40 mg of furosemide on day 4 after admission) and hemoconcentration (change in hemoglobin at discharge or day 7) were tested both individually and combined to predict the risk of HF and cardiovascular rehospitalization 60 days after hospitalization for acute HF. Analyses were performed in 1180 patients enrolled in the Placebo-Controlled Randomized Study of the Selective Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) trial and validated in 1776 patients enrolled in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Poor diuretic response was associated with low systolic blood pressure, high blood urea nitrogen, and history of coronary revascularization in both data sets (all P<0.05). Hemoconcentration was mainly associated with better renal function (P<0.05). Patients who displayed both favorable diuretic response and hemoconcentration had a markedly lower risk of rehospitalization for HF in PROTECT (multivariable HR, 0.41; 95% CI, 0.24 to 0.70; P<0.001) compared with all other patients. This finding was confirmed in EVEREST (multivariable HR, 0.52; 95% CI, 0.33 to 0.82; P=0.004) for patients with favorable diuretic response and hemoconcentration compared with all other patients. CONCLUSIONS: Combining 2 indicators of decongestion, hemoconcentration and diuretic response improves risk prediction for early rehospitalization after an admission for acute HF and may provide clinicians with an easily accessible tool to identify low-risk patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00354458 and NCT00071331. PMID- 27266855 TI - Direct Tracking of Amyloid and Tu Dynamics in Neuroblastoma Cells Using Nanoplasmonic Fiber Tip Probes. AB - Amyloid plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease. However, there has been a long-standing discussion on the dynamic relations between Abeta and tau proteins, partially due to the lack of a tool to track protein dynamics in individual live neurons at the early stage of Abeta generation and tau phosphorylation. Here, we developed nanoplasmonic fiber tip probe (nFTP) technology to simultaneously monitor Abeta42 generation and tau phosphorylation (at serine 262) in living, single neuroblastoma cells over 12 h. We observed that Abeta42 generation, under clinically relevant anesthetic treatment, preceded tau phosphorylation, which then facilitated Abeta42 generation. This observation is also supported by measuring proteins in cell lysates using the ultrasensitive label-free photonic crystal nanosensors. nFTP therefore provides an advanced method to investigate protein expression and post translational modification in live cells and determine outcomes of intervention of Alzheimer's disease and other neurodegenerative disorders. PMID- 27266856 TI - Bound Flavin-Cytochrome Model of Extracellular Electron Transfer in Shewanella oneidensis: Analysis by Free Energy Molecular Dynamics Simulations. AB - Flavins are known to enhance extracellular electron transfer (EET) in Shewanella oneidensis MR-1 bacteria, which reduce electron acceptors through outer-membrane (OM) cytochromes c. Free-shuttle and bound-redox cofactor mechanisms were proposed to explain this enhancement, but recent electrochemical reports favor a flavin-bound model, proposing two one-electron reductions of flavin, namely, oxidized (Ox) to semiquinone (Sq) and semiquinone to hydroquinone (Hq), at anodic and cathodic conditions, respectively. In this work, to provide a mechanistic understanding of riboflavin (RF) binding at the multiheme OM cytochrome OmcA, we explored binding configurations at hemes 2, 5, 7, and 10. Subsequently, on the basis of molecular dynamics (MD) simulations, binding free energies and redox potential shifts upon RF binding for the Ox/Sq and Sq/Hq reductions were analyzed. Our results demonstrated an upshift in the Ox/Sq and a downshift in the Sq/Hq redox potentials, consistent with a bound RF-OmcA model. Furthermore, binding free energy MD simulations indicated an RF binding preference at heme 7. MD simulations of the OmcA-MtrC complex interfacing at hemes 5 revealed a small interprotein redox potential difference with an electron transfer rate of 10(7) 10(8)/s. PMID- 27266857 TI - Take Charge of Pain: evaluating a community-targeted self-management education program for people with musculoskeletal pain. AB - Issue addressed Musculoskeletal conditions are highly prevalent, affecting 28% of the Australian population. Given the persistent nature of many musculoskeletal conditions self-management is recognised as an important aspect of effective disease management. However, participant recruitment and retention for formal self-management programs is a challenge. Methods Arthritis SA (Arthritis Foundation of South Australia, a non-profit community health organisation) redesigned a shorter, community-orientated self-management education program delivered by health professionals. The program utilises aspects of the Stanford model of chronic disease self-management and motivational interviewing as well as principles of adult learning to create an effective learning environment. The program aims to guide participants to learn and practise a range of pain management strategies that are known to be effective in improving quality of life. This study used a pre- and post-test (at 6 weeks) design to determine whether this program achieved benefits in self-reported health outcomes. Outcomes that were measured included pain, fatigue, health distress, self-efficacy and communication. Results A response rate of 47% (n=102) was achieved and small but statistically significant improvements in mean [s.d.] pain scores (6.1 [2.3] to 5.4 [2.4], P=0.001), health distress (2.3 [1.3] to 2.0 [1.3], P=0.002) and self efficacy (6.2 [2.1] to 6.8 [2.2], P=0.002) were found. Conclusion Community-based participants of this shorter, focused program recorded small but significant improvements in self-reported pain, health distress and self-efficacy. For those who completed the current program, Arthritis SA is currently exploring the potential of developing a booster session to promote sustainable positive health outcomes. So what? Supporting self-management through education is recognised as important but also as a key challenge for effective management of musculoskeletal conditions. Using a pre-post evaluation design, this study demonstrated effectiveness (short-term improvements for self-reported pain, health distress and self-efficacy) for a redesigned and shortened community-targeted program focusing on musculoskeletal pain. PMID- 27266858 TI - Theoretical Insights into the Catalytic Mechanism of N-Heterocyclic Olefins in Carboxylative Cyclization of Propargyl Alcohol with CO2. AB - The mechanism of carboxylative cyclization of propargyl alcohol with CO2 catalyzed by N-heterocyclic olefins (NHOs) has been studied by density functional theory calculations. The calculations reveal that the catalytic reaction tends to proceed via the NHO-mediated basic ionic pair mechanism, in which free NHO primarily acts as a basic precursor to trigger the carboxylation of propargyl alcohol with CO2, leading to a [NHOH](+)[carbonate](-) ion pair intermediate. Then, the catalytic cycle proceeds, including isomerization of the [NHOH](+)[carbonate](-) ion pair intermediate, intramolecular nucleophilic addition of the carbonate oxygen anion to the alkynyl group, and protonation of the alkenyl carbon anion with an external propargyl alcohol molecule. Molecule orbital and nature population analysis discloses that the preference for the basic ionic pair mechanism is due to the favorable orbital and charge interactions between the alpha-carbon atom of NHO and the hydroxyl hydrogen of propargyl alcohol. The [NHOH](+) cation has proven to be crucial for stabilizing the [carbonate](-) anion, which allows the reaction to proceed through a more thermodynamically stable pathway. The investigations of the effect of substituents of NHOs predict that N-substituents with a strong electron donating effect and a bulky steric effect might improve the catalytic activity of NHOs for the reaction. PMID- 27266854 TI - Predicting Heart Failure With Preserved and Reduced Ejection Fraction: The International Collaboration on Heart Failure Subtypes. AB - BACKGROUND: Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF). METHODS AND RESULTS: Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2:1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c statistic 0.80; 95% confidence interval [CI], 0.78-0.82) and validation samples (internal: 0.79; 95% CI, 0.77-0.82 and external: 0.76; 95% CI: 0.71-0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80-0.84) and validation samples (internal: 0.80; 95% CI, 0.78-0.83 and external: 0.76; 95% CI, 0.71-0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF (P value for each comparison <=0.02). CONCLUSIONS: We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes. PMID- 27266859 TI - Overdiagnosis of heart failure in primary care: a cross-sectional study. AB - BACKGROUND: Access to echocardiography in primary care is limited, but is necessary to accurately diagnose heart failure (HF). AIM: To determine the proportion of patients with a GP's diagnosis of HF who really have HF. DESIGN AND SETTING: A cross-sectional study of patients in 30 general practices with a GP's diagnosis of heart failure, based on the International Classification of Primary Care (ICPC) code K77, between June and November 2011. METHOD: Electronic medical records of the patients' GPs were scrutinised for information on the diagnosis. An expert panel consisting of two cardiologists and an experienced GP used all available diagnostic information, and established the presence or absence of HF according to the criteria of the European Society of Cardiology (ESC) HF guidelines. RESULTS: In total, 683 individuals had a GP's diagnosis of HF. The mean age was 77.9 (SD 11.4) years, and 42.2% were male. Of these 683, 79.6% received cooperative care from a cardiologist. In 73.5% of cases, echocardiography was available for panel re-evaluation. Based on consensus opinion of the panel, 434 patients (63.5%, 95% confidence interval [CI] = 59.9 to 67.1) had definite HF, of which 222 (32.5%, 95% CI = 30.9 to 34.1) had HF with a reduced ejection fraction (HFrEF), 207 (30.3%, 95% CI = 29.0 to 31.6) had HF with a preserved ejection fraction (HFpEF), and five (0.7%, 95% CI = 1.2 to 2.6) had isolated right-sided HF. In 17.3% of cases (95% CI = 14.4 to 20.0), the panel considered HF absent, and in 19.2% (95% CI = 16.3 to 22.2) the diagnosis remained uncertain. CONCLUSION: More than one-third of primary care patients labelled with HF may not have HF, and such overdiagnosis may result in inadequate patient management. PMID- 27266860 TI - Influence of ethnicity on acceptability of method of blood pressure monitoring: a cross-sectional study in primary care. AB - BACKGROUND: Ambulatory and/or home monitoring are recommended in the UK and the US for the diagnosis of hypertension but little is known about their acceptability. AIM: To determine the acceptability of different methods of measuring blood pressure to people from different minority ethnic groups. DESIGN AND SETTING: Cross-sectional study with focus groups in primary care in the West Midlands. METHOD: People of different ethnicities with and without hypertension were assessed for acceptability of clinic, home, and ambulatory blood pressure measurement using completion rate, questionnaire, and focus groups. RESULTS: A total of 770 participants were included, who were white British (n = 300), South Asian (n = 241), and African Caribbean (n = 229). White British participants had significantly higher successful completion rates across all monitoring modalities compared with the other ethnic groups, especially for ambulatory monitoring: white British (n = 277, 92% [95% confidence interval [CI] = 89% to 95%]) versus South Asian (n = 171, 71% [95% CI = 65% to 76%], P<0.001) and African Caribbean (n = 188, 82% [95% CI = 77% to 87%], P<0.001), respectively. There were significantly lower acceptability scores for minority ethnic participants across all monitoring methods compared with white British participants. Focus group results highlighted self-monitoring as most acceptable and ambulatory monitoring least acceptable without consistent differences by ethnicity. Clinic monitoring was seen as inconvenient and anxiety provoking but with the advantage of immediate professional input. CONCLUSION: Reduced acceptability and completion rates among minority ethnic groups raise important questions for the implementation and interpretation of blood pressure monitoring. Selection of method of blood pressure monitoring should take into account clinical need, patient preference, and potential cultural barriers to monitoring. PMID- 27266861 TI - Alerts in electronic medical records to promote a colorectal cancer screening programme: a cluster randomised controlled trial in primary care. AB - BACKGROUND: Participation rates in colorectal cancer screening are below recommended European targets. AIM: To evaluate the effectiveness of an alert in primary care electronic medical records (EMRs) to increase individuals' participation in an organised, population-based colorectal cancer screening programme when compared with usual care. DESIGN AND SETTING: Cluster randomised controlled trial in primary care centres of Barcelona, Spain. METHOD: Participants were males and females aged 50-69 years, who were invited to the first round of a screening programme based on the faecal immunochemical test (FIT) (n = 41 042), and their primary care professional. The randomisation unit was the physician cluster (n = 130) and patients were blinded to the study group. The control group followed usual care as per the colorectal cancer screening programme. In the intervention group, as well as usual care, an alert to health professionals (cluster level) to promote screening was introduced in the individual's primary care EMR for 1 year. The main outcome was colorectal cancer screening participation at individual participant level. RESULTS: In total, 67 physicians and 21 619 patients (intervention group) and 63 physicians and 19 423 patients (control group) were randomised. In the intention-to-treat analysis screening participation was 44.1% and 42.2% respectively (odds ratio 1.08, 95% confidence interval [CI] = 0.97 to 1.20, P = 0.146). However, in the per-protocol analysis screening uptake in the intervention group showed a statistically significant increase, after adjusting for potential confounders (OR, 1.11; 95% CI = 1.02 to 1.22; P = 0.018). CONCLUSION: The use of an alert in an individual's primary care EMR is associated with a statistically significant increased uptake of an organised, FIT-based colorectal cancer screening programme in patients attending primary care centres. PMID- 27266862 TI - Medication management strategy for older people with polypharmacy in general practice: a qualitative study on prescribing behaviour in primary care. AB - BACKGROUND: For older patients with polypharmacy, medication management is a process of careful deliberation that needs periodic adjustment based on treatment effects and changing conditions. Because of the heterogeneity of the patient group, and limited applicability of current guidelines, it is difficult for GPs to build up a routine. AIM: To gain insight into GPs' medication management strategies for patients with polypharmacy, and to explore the GPs' perspectives and needs on decision-making support to facilitate this medication management. DESIGN AND SETTING: Two focus group meetings with Dutch GPs, discussing four clinical vignettes of patients with multimorbidity and polypharmacy. METHOD: Questions about medication management of the vignettes were answered individually; the strategy chosen in each case was discussed in plenary. Analysis followed a Framework approach. RESULTS: In total, 12 GPs described a similar strategy regarding the patients' medication management: defining treatment goals; determining primary goals; and adjusting medications based on the treatment effect, GPs' and patients' preferences, and patient characteristics. There was variation in the execution of this strategy between the GPs. The GPs would like to discuss their choices with other professionals and they valued structured medication reviews with the patient, as well as quick and practical support tools that work on demand. CONCLUSION: To facilitate decision making, a more extensive and structured collaboration between healthcare professionals is desired, as well as support to execute structured medication reviews with eligible patients, and some on-demand tools for individual consultations. PMID- 27266863 TI - Faecal calprotectin in patients with suspected colorectal cancer: a diagnostic accuracy study. AB - BACKGROUND: NICE guidance exists for the use of faecal calprotectin (FC) when irritable bowel syndrome or inflammatory bowel disease are suspected. Often, however, colorectal cancer is considered within the differential. Should FC have a high diagnostic accuracy for colorectal cancer, it may be applicable as a primary care screening test for all patients with lower gastrointestinal symptoms. AIM: To determine the negative and positive predictive value (NPV/PPV) of FC in patients referred from primary care with suspected colorectal cancer. DESIGN AND SETTING: A diagnostic accuracy study conducted at a single secondary care site METHOD: Consenting patients referred with suspected colorectal cancer within the '2-week wait' pathway provided a stool sample for FC prior to investigation. FC levels were reconciled with end diagnoses: cancer, adenomatous polyps >=10 mm, and all enteric organic disease. RESULTS: A total of 654 patients completed the evaluation; median age 69 years, female 56%. The NPV for colorectal cancer was 98.6% and 97.2% when including polyps >=10 mm. The PPV for all organic enteric disease was 32.7%. The diagnostic yield for cancer based on clinical suspicion was 6.3%. By altering the FC cut-off to fix the NPV at 97.0%, the PPV for cancer increased from 8.7% to 13.3%. CONCLUSION: FC has a high NPV for colorectal cancer and significant polyps in patients with suspected cancer. In total, 27.8% of patients had a normal FC and could safely have been spared a '2 week wait' referral. The addition of FC testing into the current symptom-based assessment has the potential to increase colorectal cancer detection rate yet be clinically and cost effective. PMID- 27266864 TI - Prevention of hospital-acquired thrombosis from a primary care perspective: a qualitative study. AB - BACKGROUND: Although there is considerable risk for patients from hospital acquired thrombosis (HAT), current systems for reducing this risk appear inefficient and have focused predominantly on secondary care, leaving the role of primary care underexplored, despite the onset of HAT often occurring post discharge. AIM: To gain an understanding of the perspectives of primary care clinicians on their contribution to the prevention of HAT. Their current role, perceptions of patient awareness, the barriers to better care, and suggestions for how these may be overcome were discussed. DESIGN AND SETTING: Qualitative study using semi-structured interviews in Oxfordshire and South Birmingham, England. METHOD: Semi-structured telephone interviews with clinicians working at practices of a variety of size, socioeconomic status, and geographical location. RESULTS: A number of factors that influenced the management of HAT emerged, including patient characteristics, a lack of clarity of responsibility, limited communication and poor coordination, and the constraints of limited practice resources. Suggestions for improving the current system include a broader role for primary care supported by appropriate training and the requisite funding. CONCLUSION: The role of primary care remains limited, despite being ideally positioned to either raise patient awareness before admission or support patient adherence to the thromboprophylaxis regimen prescribed in hospital. This situation may begin to be addressed by more robust lines of communication between secondary and primary care and by providing more consistent training for primary care staff. In turn, this relies on the allocation of appropriate funds to allow practices to meet the increased demand on their time and resources. PMID- 27266865 TI - Beliefs and attitudes of older adults and carers about deprescribing of medications: a qualitative focus group study. AB - BACKGROUND: Deprescribing describes the complex process that is required for the safe and effective cessation of medications that are likely to cause more harm than benefit. Knowledgeof older adults' and carers' attitudes towards deprescribing will enhance shared decision making in medication optimisation. AIM: To explore the views, beliefs, and attitudes of older adults and carers on deprescribing. DESIGN AND SETTING: Qualitative focus group study in New South Wales, Australia. METHOD: Four focus groups with 14 older adults and 14 carers were conducted. Results were analysed using a previously developed framework (directed content analysis) with additional conventional content analysis. RESULTS: The willingness of both older adults and carers to have one or more medications deprescribed was influenced by the following main themes: their perception of the appropriateness of that medication; fear of outcomes of withdrawal; dislike of taking medications; and the availability of a process for withdrawal (including a discussion with a healthcare professional and knowing that the medication could be restarted if necessary). A patient's regular GP was identified as a strong influence both for and against medication withdrawal. The identified themes supported the previously developed framework. An additional theme unique to the carers was the complexity involved in making decisions about medications for their care recipients. CONCLUSION: This study highlights that discussions between the healthcare professional and the olderadult or carer about withdrawing medications should address reasons for deprescribing. GPs should be aware of their major influence on patients and regularly discuss appropriateness of current medication use with older adults and their carers. PMID- 27266866 TI - Focal seizures in a patient with myotonic disorder type 2 co-segregating with a chloride voltage-gated channel 1 gene mutation: a case report. AB - BACKGROUND: Myotonic dystrophy type 2 is a multisystem disorder with both neurological and non-neurological signs and symptoms. Seizures are not a commonly associated neurological feature of this disorder. CASE PRESENTATION: A 57-year old white American man presented with a long history of clinical and electrophysiological features of a myotonic disorder. He also developed multiple episodes of focal seizures and underwent a series of investigations which showed no structural or metabolic etiology. Genetic testing revealed that he had an expansion mutation in CCHC-type zinc finger, nucleic acid binding protein gene confirming the diagnosis of myotonic disorder type 2 and carried a mutation in the chloride voltage-gated channel 1 gene. CONCLUSIONS: We report a rare association between myotonic dystrophy type 2 and a seizure disorder. The pathophysiology of a possible relationship between these two neurological conditions is discussed. PMID- 27266867 TI - The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial. AB - BACKGROUND: Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. METHODS/DESIGN: This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. DISCUSSION: This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013. PMID- 27266868 TI - A cluster randomized trial of a transition intervention for adolescents with congenital heart disease: rationale and design of the CHAPTER 2 study. AB - BACKGROUND: The population of adolescents and young adults with congenital heart disease (CHD) is growing exponentially. These survivors are at risk of late cardiac complications and require lifelong cardiology care. However, there is a paucity of data on how to prepare adolescents to assume responsibility for their health and function within the adult health care system. Evidence-based transition strategies are required. METHODS: The Congenital Heart Adolescents Participating in Transition Evaluation Research (CHAPTER 2) Study is a two-site cluster randomized clinical trial designed to evaluate the efficacy of a nurse led transition intervention for 16-17 year olds with moderate or complex CHD. The primary endpoint is excess time to adult CHD care, defined as the time interval between the final pediatric cardiology appointment and the first adult CHD appointment, minus the recommended time interval between these appointments. Secondary endpoints include the MyHeart score (CHD knowledge), Transition Readiness Assessment Questionnaire score, and need for catheter or surgical re intervention. Participants are enrolled in clusters based on week of attendance in the pediatric cardiology clinic. The intervention consists of two one-hour individualized sessions between a cardiology nurse and study participant. Session One focuses on knowledge of the participant's CHD, review of their cardiac anatomy and prior interventions, and potential late cardiac complications. Session Two focuses on self-management and communication skills through review and discussion of videos and role-play. The study will recruit 120 participants. DISCUSSION: Many adolescents and young adults experience a gap in care predisposing them to late cardiac complications. The CHAPTER 2 Study will investigate the impact of a nurse-led transition intervention among adolescents with CHD. Fidelity of the intervention is a major focus and priority. This study will build on our experience by (i) enrolling at two tertiary care programs, (ii) including a self-management intervention component, and (iii) evaluating the impact of the intervention on time to ACHD care, a clinically relevant outcome. The results of this study will inform pediatric cardiology programs, patients and policy makers in judging whether a structured intervention program provides clinically meaningful outcomes for adolescents and young adults living with CHD. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01723332. PMID- 27266869 TI - Beyond type 2 diabetes, obesity and hypertension: an axis including sleep apnea, left ventricular hypertrophy, endothelial dysfunction, and aortic stiffness among Mexican Americans in Starr County, Texas. AB - BACKGROUND: There is an increasing appreciation for a series of less traditional risk factors that should not be ignored when considering type 2 diabetes, obesity, hypertension, and cardiovascular disease. These include aortic stiffness, cardiac structure, impaired endothelial function and obstructive sleep apnea. They are associated to varying degrees with each disease categorization and with each other. It is not clear whether they represent additional complications, concomitants or antecedents of disease. Starr County, Texas, with its predominantly Mexican American population has been shown previously to bear a disproportionate burden of the major disease categories, but little is known about the distribution of these less traditional factors. METHODS: Type 2 diabetes, obesity and hypertension frequencies were determined through a systematic survey of Starr County conducted from 2002 to 2006. Individuals from this examination and an enriched set with type 2 diabetes were re-examined from 2010 to 2014 including assessment of cardiac structure, sleep apnea, endothelial function and aortic stiffness. Individual and combined frequencies of these inter related (i.e., axis) conditions were estimated and associations evaluated. RESULTS: Household screening of 5230 individuals aged 20 years and above followed by direct physical assessment of 1610 identified 23.7 % of men and 26.7 % of women with type 2 diabetes, 46.2 and 49.5 % of men and women, respectively with obesity and 32.1 and 32.4 % with hypertension. Evaluation of pulse wave velocity, left ventricular mass, endothelial function and sleep apnea identified 22.3, 12.7, 48.6 and 45.2 % of men as having "at risk" values for each condition, respectively. Corresponding numbers in women were 16.0, 17.9, 23.6 and 28.8 %. Cumulatively, 88 % of the population has one or more of these while 50 % have three or more. CONCLUSIONS: The full axis of conditions is high among Mexican Americans in Starr County, Texas. Individual and joint patterns suggest a genesis well before overt disease. Whether they are all mediated by common underlying factors or whether there exist multiple mechanisms remains to be seen. PMID- 27266870 TI - The association between intraocular pressure and different combination of metabolic syndrome components. AB - BACKGROUND: Although the association between metabolic syndrome and intraocular pressure is well known, the relationship between the intraocular pressure and different combination of the components of metabolic syndrome has not been actively researched yet. The study aimed to investigate the relationship between the intraocular pressure and metabolic syndrome components with their different combinations. METHODS: Thirty-one thousand two hundred seventy one healthy people aged 19-79 who attended a community hospital for a health check-up between January 2011 and December 2013 were enrolled in the study. Subjects with a history of intraocular disease, at least in one eye and those receiving medical treatment for glaucoma were excluded. Metabolic syndrome was diagnosed following the criteria defined in Circulation 2009. RESULTS: Subjects with combination of three metabolic syndrome components of triglycerides, abdominal obesity, and fasting glucose had the highest intraocular pressure. And subjects with the combination of four components of blood pressure, high-density lipoproteins, triglycerides, fasting glucose had a significantly higher intraocular pressure than ones with the combination of all five metabolic syndrome components. CONCLUSIONS: The difference in the risk of high intraocular pressure according to the different combination of the metabolic syndrome components could be confirmed. If additional follow-up studies are conducted, the findings can be used as an indicator for predicting intraocular pressure increases in patients with metabolic syndrome. PMID- 27266871 TI - The effect of using blood culture bottle of bronchoalveolar larvage fluid in pneumonia. AB - BACKGROUND: Pneumonia is a primary cause of morbidity and mortality in infectious disease, and increasing antimicrobial resistance has raised concerns of treatment failure. Therefore, we evaluated the value of a blood culture bottle for bronchoalveolar lavage (BAL) samples on pathogen identification and on treatment modification in patients with pneumonia. METHODS: We conducted a prospective study and enrolled 39 patients who were hospitalized for pneumonia. Enrolled patients underwent BAL; a 10-ml aliquot was transferred to a sterile container for standard quantitative culture, and a 5 ml aliquot was transferred to both an aerobic and an anaerobic blood culture bottle. RESULTS: Microbes were detected in all 39 (100 %) specimens and possible pathogens were identified in 34 patients (84.6 %) from BAL blood culture bottles. In contrast, microbes were detected in 10 patients (25.6 %) and possible pathogens were isolated in 8 patients (20.5 %) in BAL fluid using conventional culture methods. Finally, 8 of 39 (20.5 %) patients changed antibiotics according to the BAL blood culture results and pneumonia improved in 6 of these patients. CONCLUSIONS: Using blood culture bottles for BAL sampling in patients with pneumonia is a sensitive method to detect pathogens in order to identify an adequate antibiotic treatment regimen. PMID- 27266872 TI - High molecular weight of polysaccharides from Hericium erinaceus against amyloid beta-induced neurotoxicity. AB - BACKGROUND: Hericium erinaceus (HE) is a well-known mushroom in traditional Chinese food and medicine. HE extracts from the fruiting body and mycelia not only exhibit immunomodulatory, antimutagenic and antitumor activity but also have neuroprotective properties. Here, we purified HE polysaccharides (HEPS), composed of two high molecular weight polysaccharides (1.7 * 10(5) Da and 1.1 * 10(5) Da), and evaluated their protective effects on amyloid beta (Abeta)-induced neurotoxicity in rat pheochromocytoma PC12 cells. METHODS: HEPS were prepared and purified using a 95 % ethanol extraction method. The components of HEPS were analyzed and the molecular weights of the polysaccharides were determined using high-pressure liquid chromatography (HPLC). The neuroprotective effects of the polysaccharides were evaluated through a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and an MTT assay and by quantifying reactive oxygen species (ROS) and mitochondrial membrane potentials (MMP) of Abeta-induced neurotoxicity in cells. RESULT: Our results showed that 250 MUg/ml HEPS was harmless and promoted cell viability with 1.2 MUM Abeta treatment. We observed that the free radical scavenging rate exceeded 90 % when the concentration of HEPS was higher than 1 mg/mL in cells. The HEPS decreased the production of ROS from 80 to 58 % in a dose-dependent manner. Cell pretreatment with 250 MUg/mL HEPS significantly reduced Abeta-induced high MMPs from 74 to 51 % and 94 to 62 % at 24 and 48 h, respectively. Finally, 250 MUg/mL of HEPS prevented Abeta-induced cell shrinkage and nuclear degradation of PC12 cells. CONCLUSION: Our results demonstrate that HEPS exhibit antioxidant and neuroprotective effects on Abeta induced neurotoxicity in neurons. PMID- 27266873 TI - Estimating micro area behavioural risk factor prevalence from large population based surveys: a full Bayesian approach. AB - BACKGROUND: An important public health goal is to decrease the prevalence of key behavioural risk factors, such as tobacco use and obesity. Survey information is often available at the regional level, but heterogeneity within large geographic regions cannot be assessed. Advanced spatial analysis techniques are demonstrated to produce sensible micro area estimates of behavioural risk factors that enable identification of areas with high prevalence. METHODS: A spatial Bayesian hierarchical model was used to estimate the micro area prevalence of current smoking and excess bodyweight for the Erie-St. Clair region in southwestern Ontario. Estimates were mapped for male and female respondents of five cycles of the Canadian Community Health Survey (CCHS). The micro areas were 2006 Census Dissemination Areas, with an average population of 400-700 people. Two individual level models were specified: one controlled for survey cycle and age group (model 1), and one controlled for survey cycle, age group and micro area median household income (model 2). Post-stratification was used to derive micro area behavioural risk factor estimates weighted to the population structure. SaTScan analyses were conducted on the granular, postal-code level CCHS data to corroborate findings of elevated prevalence. RESULTS: Current smoking was elevated in two urban areas for both sexes (Sarnia and Windsor), and an additional small community (Chatham) for males only. Areas of excess bodyweight were prevalent in an urban core (Windsor) among males, but not females. Precision of the posterior post-stratified current smoking estimates was improved in model 2, as indicated by narrower credible intervals and a lower coefficient of variation. For excess bodyweight, both models had similar precision. Aggregation of the micro area estimates to CCHS design-based estimates validated the findings. CONCLUSIONS: This is among the first studies to apply a full Bayesian model to complex sample survey data to identify micro areas with variation in risk factor prevalence, accounting for spatial correlation and other covariates. Application of micro area analysis techniques helps define areas for public health planning, and may be informative to surveillance and research modeling of relevant chronic disease outcomes. PMID- 27266874 TI - Detection of differentially expressed candidate genes for a fatty liver QTL on mouse chromosome 12. AB - BACKGROUND: The SMXA-5 mouse is an animal model of high-fat diet-induced fatty liver. The major QTL for fatty liver, Fl1sa on chromosome 12, was identified in a SM/J * SMXA-5 intercross. The SMXA-5 genome consists of the SM/J and A/J genomes, and the A/J allele of Fl1sa is a fatty liver-susceptibility allele. The existence of the responsible genes for fatty liver within Fl1sa was confirmed in A/J-12(SM) consomic mice. The aim of this study was to identify candidate genes for Fl1sa, and to investigate whether the identified genes affect the lipid metabolism. RESULTS: A/J-12(SM) mice showed a significantly lower liver triglyceride content compared to A/J mice when fed the high-fat diet for 7 weeks. We detected differences in the accumulation of liver lipids in response to the high-fat diet between A/J and A/J-12(SM) consomic mice. To identify candidate genes for Fl1sa, we performed DNA microarray analysis using the livers of A/J-12(SM) and A/J mice fed the high-fat diet. The mRNA levels of three genes (Iah1, Rrm2, Prkd1) in the chromosomal region of Fl1sa were significantly different between the strains. Iah1 mRNA levels in the liver, kidney, and lung were significantly higher in A/J 12(SM) mice than in A/J mice. The hepatic Iah1 mRNA level in A/J-12(SM) mice was 3.2-fold higher than that in A/J mice. To examine the effect of Iah1 on hepatic lipid metabolism, we constructed a stable cell line expressing the mouse Iah1 protein in mouse hepatoma Hepa1-6 cells. Overexpression of Iah1 in Hepa1-6 cells suppressed the mRNA levels of Cd36 and Dgat2, which play important roles in triglyceride synthesis and lipid metabolism. CONCLUSIONS: These results demonstrated that Fl1sa on the proximal region of chromosome 12 affected fatty liver in mice on a high-fat diet. Iah1 (isoamyl acetate-hydrolyzing esterase 1 homolog) was identified as one of the candidate genes for Fl1sa. This study revealed that the mouse Iah1 gene regulated the expression of genes related to lipid metabolism in the liver. PMID- 27266876 TI - High fat Mediterranean diet is not linked to greater weight gain than low fat diet. PMID- 27266877 TI - Lanostane Triterpenes Isolated from Antrodia heteromorpha and Their Inhibitory Effects on RANKL-Induced Osteoclastogenesis. AB - Two new spiro-lanostane triterpenoids, antrolactones A and B (1 and 2), along with polyporenic acid C (3), were isolated from an EtOAc-soluble extract of Antrodia heteromorpha culture medium, and the chemical structures of the new compounds were elucidated by application of NMR, MS, and ECD spectroscopic techniques. All isolated compounds exhibited inhibitory effects on receptor activator of nuclear factor-kappaB ligand-induced osteoclastogenesis. PMID- 27266875 TI - Expression of IL-1beta in rhesus EAE and MS lesions is mainly induced in the CNS itself. AB - BACKGROUND: Interleukin (IL)-1beta is a pro-inflammatory cytokine that plays a role in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Yet, detailed studies on IL 1beta expression in different stages of MS lesion development and a comparison of IL-1beta expression in MS and EAE are lacking. METHODS: Here, we performed an extensive characterization of IL-1beta expression in brain tissue of MS patients, which included different MS lesion types, and in brain tissue of rhesus macaques with EAE. RESULTS: In rhesus EAE brain tissue, we observed prominent IL-1beta staining in MHC class II(+) cells within perivascular infiltrates and at the edges of large demyelinating lesions. Surprisingly, staining was localized to resident microglia or differentiated macrophages rather than to infiltrating monocytes, suggesting that IL-1beta expression is induced within the central nervous system (CNS). By contrast, IL-1beta staining in MS brain tissue was much less pronounced. Staining was found in the parenchyma of active and chronic active MS lesions and in nodules of MHC class II(+) microglia in otherwise normal appearing white matter. IL-1beta expression was detected in a minority of the nodules only, which could not be distinguished by the expression of pro- and anti inflammatory markers. These nodules were exclusively found in MS, and it remains to be determined whether IL-1beta(+) nodules are destined to progress into active lesions or whether they merely reflect a transient response to cellular stress. CONCLUSIONS: Although the exact localization and relative intensity of IL-1beta expression in EAE and MS is different, the staining pattern in both neuroinflammatory disorders is most consistent with the idea that the expression of IL-1beta during lesion development is induced in the tissue rather than in the periphery. PMID- 27266878 TI - Catastrophic expenditure and impoverishment of patients affected by 7 rare diseases in China. AB - BACKGROUND: China is actively promoting regulation of rare diseases, rare disease and orphan drugs have been formally incorporated into the national planning. However, few studies have been done to evaluate the affordability of rare disease patients in China. This study aims to provide policy recommendations for the establishment of social security mechanism for rare diseases in China, so as to address the problem of poverty caused by these diseases. METHODS: A total of 7 rare diseases were selected by Delphi method. Affordability of treatment for the 7 rare diseases was assessed through annual per capital income, catastrophic expenditure and impoverishment expenditure among urban and rural residents in China. RESULTS: Assessed through annual per capital income, health expenditure for the 7 rare diseases are all rather high. The highest health expenditure is equivalent to income of 69.34 years of one urban resident, and the burden is heavier for rural residents. Through catastrophic expenditure assessment, proportions of the population experiencing catastrophic expenditure caused by the 7 rare diseases are all under 0.167 0/00. However, once one is ill and taking medications, he will suffer from catastrophic health expenditure. Through impoverishment expenditure assessment, the proportions of impoverishment payment are low among both urban and rural residents, but the 7 rare diseases could lead nearly 4.6 million people into poverty on a national scale. CONCLUSION: The affordability of treatment for rare disease as well as orphan drugs is rather poor. Residents of different income levels all have difficulties to afford the treatment for rare diseases, so poverty caused by rare diseases is quite widespread. Therefore, social security mechanism for rare disease patients should be established and specific payment pattern for orphan drugs should be set up. PMID- 27266879 TI - Validity and reliability of intraoral scanners compared to conventional gypsum models measurements: a systematic review. AB - BACKGROUND: The development of 3D technology and the trend of increasing the use of intraoral scanners in dental office routine lead to the need for comparisons with conventional techniques. OBJECTIVE: To determine if intra- and inter-arch measurements from digital dental models acquired by an intraoral scanner are as reliable and valid as the similar measurements achieved from dental models obtained through conventional intraoral impressions. SEARCH METHODS: An unrestricted electronic search of seven databases until February 2015. SELECTION CRITERIA: Studies that focused on the accuracy and reliability of images obtained from intraoral scanners compared to images obtained from conventional impressions. DATA COLLECTION AND ANALYSIS: After study selection the QUADAS risk of bias assessment tool for diagnostic studies was used to assess the risk of bias (RoB) among the included studies. RESULTS: Four articles were included in the qualitative synthesis. The scanners evaluated were OrthoProof, Lava, iOC intraoral, Lava COS, iTero and D250. These studies evaluated the reliability of tooth widths, Bolton ratio measurements, and image superimposition. Two studies were classified as having low RoB; one had moderate RoB and the remaining one had high RoB. Only one study evaluated the time required to complete clinical procedures and patient's opinion about the procedure. Patients reported feeling more comfortable with the conventional dental impression method. LIMITATIONS: Associated costs were not considered in any of the included study. CONCLUSIONS AND IMPLICATIONS: Inter- and intra-arch measurements from digital models produced from intraoral scans appeared to be reliable and accurate in comparison to those from conventional impressions. This assessment only applies to the intraoral scanners models considered in the finally included studies. Digital models produced by intraoral scan eliminate the need of impressions materials; however, currently, longer time is needed to take the digital images. REGISTRATION: PROSPERO (CRD42014009702). FUNDING: None. PMID- 27266880 TI - Variations in the recruitment of syntactic knowledge contribute to SES differences in syntactic development. AB - Average differences in children's language abilities by socioeconomic status (SES) emerge early in development and predict academic achievement. Previous research has focused on coarse-grained outcome measures such as vocabulary size, but less is known about the extent to which SES differences exist in children's strategies for comprehension and learning. We measured children's (N = 98) comprehension of passive sentences to investigate whether SES differences are more pronounced in overall knowledge of the construction or in more specific abilities to process sentences during real-time interpretation. SES differences in comprehension emerged when syntactic revision of passives was necessary, and disappeared when the need to revise was removed. Further, syntactic revision but not knowledge of the passive best explained the association between SES and a standardized measure of syntactic development. These results demonstrate that SES differences in syntactic development may result from how children recruit syntactic information within sentences. PMID- 27266881 TI - Attenuated LKB1-SIK1 signaling promotes epithelial-mesenchymal transition and radioresistance of non-small cell lung cancer cells. AB - BACKGROUND: Radiotherapy is one of the main therapeutic approaches for non-small cell lung cancer (NSCLC). However, radioresistant cancer cells can eventually cause tumor relapse and even fatal metastasis. It is thought that radioresistance and metastasis could be potentially linked by epithelial-mesenchymal transition (EMT). In this study, we established radioresistant NSCLC cells to investigate the potential relationship among radioresistance, EMT, and enhanced metastatic potential and the underlying mechanism involving liver kinase B1 (LKB1)-Salt inducible kinase 1 (SIK1) signaling. METHODS: The radioresistant cell lines A549R and H1299R were generated by dose-gradient irradiation of the parental A549 and H1299 cells. The radioresistance/sensitivity was evaluated by Cell Counting Kit-8 assay, apoptosis analysis, and/or clonogenic cell survival assay. The EMT phenotype and the signaling change were assessed by Western blotting. The abilities of invasion and migration were evaluated by transwell assays and wound healing assays. RESULTS: The radioresistant cell lines A549R and H1299R displayed mesenchymal features with enhanced invasion and migration. Mechanistically, A549R and H1299R cells had attenuated LKB1-SIK1 signaling, which leaded to the up regulation of Zinc-finger E-box-binding homeobox factor 1 (ZEB1)--a transcription factor that drives EMT. Re-expression of LKB1 in A549R cells reversed the EMT phenotype, whereas knockdown of LKB1 in H1299R cells further promoted the EMT phenotype. Moreover, re-expression of LKB1 in A549 cells increased the radiosensitivity, whereas knockdown of LKB1 in H1299 cells decreased the radiosensitivity. CONCLUSIONS: Our findings suggest that attenuated LKB1-SIK1 signaling promotes EMT and radioresistance of NSCLC cells, which subsequently contributes to the enhanced metastatic potential. Targeting the LKB1-SIK1-ZEB1 pathway to suppress EMT might provide therapeutic benefits. PMID- 27266882 TI - Luteolin Impacts on the DNA Damage Pathway in Oral Squamous Cell Carcinoma. AB - Oral squamous cell carcinoma (OSCC) exhibited high chemoresistance to current treatments. Here we aimed at identifying and repositioning approved drugs that could be selectively toxic toward OSCC cells. Through a cell-based drug screening of 1,280 chemical molecules, we selected compounds lethal to oral cancer SCC-25 cells, while sparing normal keratinocyte HaCaT cells. Within the chemical library, the natural flavonoid luteolin was identified as a potent cytotoxic agent against oral cancer cells in vitro, along with metixene hydrochloride and nitazoxanide. Of note, they exhibit low toxicity and high efficiency compared to the standard-of-care, such as cisplatin and the epidermal growth factor receptor inhibitor tyrphostin. From a molecular standpoint, luteolin causes phosphorylation of ataxia telangiectasia mutated (ATM) and H2AX in a DNA repair pathway and can be efficiently combined with a checkpoint kinase (CHK) pharmacological inhibitor. Thus, luteolin emerges as a potent cytotoxic and/or adjuvant therapy in oral cancer, as it is a natural compound presenting better effects in vitro compared to conventional chemotherapeutic agents. Future in vivo exploration is next required to provide the proof-of-concept that luteolin could be an efficient anticancer molecule. PMID- 27266883 TI - Kinesio Taping Does Not Provide Additional Benefits in Patients With Chronic Low Back Pain Who Receive Exercise and Manual Therapy: A Randomized Controlled Trial. AB - Study Design Randomized controlled trial. Background Many clinical practice guidelines endorse both manual therapy and exercise as effective treatment options for patients with low back pain. To optimize the effects of the treatments recommended by the guidelines, a new intervention known as Kinesio Taping is being widely used in these patients. Objectives To determine the effectiveness of Kinesio Taping in patients with chronic nonspecific low back pain when added to a physical therapy program consisting of exercise and manual therapy. Methods One hundred forty-eight patients with chronic nonspecific low back pain were randomly allocated to receive 10 (twice weekly) sessions of physical therapy, consisting of exercise and manual therapy, or the same treatment with the addition of Kinesio Taping applied to the lower back. The primary outcomes were pain intensity and disability (5 weeks after randomization) and the secondary outcomes were pain intensity, disability (3 months and 6 months after randomization), global perceived effect, and satisfaction with care (5 weeks after treatment). Data were collected by a blinded assessor. Results No between-group differences were observed in the primary outcomes of pain intensity (mean difference, -0.01 points; 95% confidence interval [CI]: -0.88, 0.85) or disability (mean difference, 1.14 points; 95% CI: -0.85, 3.13) at 5 weeks' follow up. In addition, no between-group differences were observed for any of the other outcomes evaluated, except for disability 6 months after randomization (mean difference, 2.01 points; 95% CI: 0.03, 4.00) in favor of the control group. Conclusion Patients who received a physical therapy program consisting of exercise and manual therapy did not get additional benefit from the use of Kinesio Taping. Level of Evidence Therapy, level 1b. Prospectively registered May 28, 2013 at www.ClinicalTrials.gov (NCT01866332). J Orthop Sports Phys Ther 2016;46(7):506-513. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6590. PMID- 27266884 TI - The Effectiveness of Physical Agents for Lower-Limb Soft Tissue Injuries: A Systematic Review. AB - Study Design Systematic review. Background Soft tissue injuries to the lower limb bring a substantial health and economic burden to society. Physical agents are commonly used to treat these injuries. However, the effectiveness of many such physical agents is not clearly established in the literature. Objective To evaluate the effectiveness and safety of physical agents for soft tissue injuries of the lower limb. Methods We searched 5 databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies. Paired reviewers independently screened the retrieved literature and appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a high risk of bias were excluded. We synthesized low-risk-of-bias studies according to principles of best-evidence synthesis. Results We screened 10261 articles. Of 43 RCTs identified, 20 had a high risk of bias and were excluded from the analysis, and 23 RCTs had a low risk of bias and were included in the analysis. The available higher-quality evidence suggests that patients with persistent plantar fasciitis may benefit from ultrasound or foot orthoses, while those with persistent midportion Achilles tendinopathy may benefit from shockwave therapy. However, the current evidence does not support the use of shockwave therapy for recent plantar fasciitis, low-Dye taping for persistent plantar fasciitis, low-level laser therapy for recent ankle sprains, or splints for persistent midportion Achilles tendinopathy. Finally, evidence on the effectiveness of the following interventions is not established in the current literature: (1) shockwave therapy for persistent plantar fasciitis, (2) cryotherapy or assistive devices for recent ankle sprains, (3) braces for persistent midportion Achilles tendinopathy, and (4) taping or electric muscle stimulation for patellofemoral pain syndrome. Conclusion Almost half the identified RCTs that evaluated the effectiveness of physical agents for the management of lower-limb soft tissue injuries had a high risk of bias. High quality RCTs are still needed to assess the effectiveness of physical agents for managing the broad range of lower-limb soft tissue injuries. The effectiveness of most interventions remains unclear. Level of Evidence Therapy, 1a. Protocol registered July 10, 2014 with PROSPERO (CRD42014010621). J Orthop Sports Phys Ther 2016;46(7):523-554. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6521. PMID- 27266885 TI - The Effect of Velocity of Joint Mobilization on Corticospinal Excitability in Individuals With a History of Ankle Sprain. AB - Study Design Controlled laboratory study. Background Joint mobilization and manipulation decrease pain and improve patient function. Yet, the processes underlying these changes are not well understood. Measures of corticospinal excitability provide insight into potential mechanisms mediated by the central nervous system. Objectives To investigate the differential effects of joint mobilization and manipulation at the talocrural joint on corticospinal excitability in individuals with resolved symptoms following ankle sprain. Methods Twenty-seven participants with a history of ankle sprain were randomly assigned to the control, joint mobilization, or thrust manipulation group. The motor-evoked potential (MEP) and cortical silent period (CSP) of the tibialis anterior and gastrocnemius were obtained with transcranial magnetic stimulation at rest and during active contraction of the tibialis anterior. The slopes of MEP/CSP input/output curves and the maximal MEP/CSP values were calculated to indicate corticospinal excitability. Behavioral measures, including ankle dorsiflexion and dynamic balance, were evaluated. Results A repeated-measures analysis of variance of the MEP slope showed a significant group-by-time interaction for the tibialis anterior at rest (P = .002) and during active contraction (P = .042). After intervention, the thrust manipulation group had an increase in corticospinal excitability, while the corticospinal excitability decreased in the mobilization group. The thrust manipulation group, but not other groups, also demonstrated a significant increase in the maximal MEP amplitude of the tibialis anterior after intervention. Conclusion The findings suggest that joint manipulation and mobilization have different effects on corticospinal excitability. The increased corticospinal excitability following thrust manipulation may provide a window for physical therapists to optimize muscle recruitment and subsequently movement. The trial was registered at ClinicalTrials.gov (NCT00847769). J Orthop Sports Phys Ther 2016;46(7):562-570. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6602. PMID- 27266886 TI - Reliability of a Qualitative Video Analysis for Running. AB - Study Design Reliability study. Background Video analysis of running gait is frequently performed in orthopaedic and sports medicine practices to assess biomechanical factors that may contribute to injury. However, the reliability of a whole-body assessment has not been determined. Objective To determine the intrarater and interrater reliability of the qualitative assessment of specific running kinematics from a 2-dimensional video. Methods Running-gait analysis was performed on videos recorded from 15 individuals (8 male, 7 female) running at a self-selected pace (3.17 +/- 0.40 m/s, 8:28 +/- 1:04 min/mi) using a high-speed camera (120 frames per second). These videos were independently rated on 2 occasions by 3 experienced physical therapists using a standardized qualitative assessment. Fifteen sagittal and frontal plane kinematic variables were rated on a 3- or 5-point categorical scale at specific events of the gait cycle, including initial contact (n = 3) and midstance (n = 9), or across the full gait cycle (n = 3). The video frame number corresponding to each gait event was also recorded. Intrarater and interrater reliability values were calculated for gait-event detection (intraclass correlation coefficient [ICC] and standard error of measurement [SEM]) and the individual kinematic variables (weighted kappa [kappaw]). Results Gait-event detection was highly reproducible within raters (ICC = 0.94-1.00; SEM, 0.3-1.0 frames) and between raters (ICC = 0.77-1.00; SEM, 0.4-1.9 frames). Eleven of the 15 kinematic variables demonstrated substantial (kappaw = 0.60-0.799) or excellent (kappaw>0.80) intrarater agreement, with the exception of foot-to-center-of-mass position (kappaw = 0.59), forefoot position (kappaw = 0.58), ankle dorsiflexion at midstance (kappaw = 0.49), and center-of mass vertical excursion (kappaw = 0.36). Interrater agreement for the kinematic measures varied more widely (kappaw = 0.00-0.85), with 5 variables showing substantial or excellent reliability. Conclusion The qualitative assessment of specific kinematic measures during running can be reliably performed with the use of a high-speed video camera. Detection of specific gait events was highly reproducible, as were common kinematic variables such as rearfoot position, foot strike pattern, tibial inclination angle, knee flexion angle, and forward trunk lean. Other variables should be used with caution. J Orthop Sports Phys Ther 2016;46(7):556-561. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6280. PMID- 27266887 TI - Treatment of Progressive First Metatarsophalangeal Hallux Valgus Deformity: A Biomechanically Based Muscle-Strengthening Approach. AB - Synopsis Hallux valgus is a progressive deformity of the first metatarsophalangeal joint that changes the anatomy and biomechanics of the foot. To date, surgery is the only treatment to correct this deformity, though the recurrence rate is as high as 15%. This clinical commentary provides instruction in a strengthening approach for treatment of hallux valgus deformity, by addressing the moment actions of 5 muscles identified as having the ability to counter the hallux valgus process. Unlike surgery, muscle strengthening does not correct the deformity, but, instead, reduces the pain and associated gait impairments that affect the mobility of people who live with the disorder. This review is organized in 4 parts. Part 1 defines the terms of foot motion and posture. Part 2 details the anatomy and biomechanics, and describes how the foot is changed with deformity. Part 3 details the muscles targeted for strengthening; the intrinsics being the abductor hallucis, adductor hallucis, and the flexor hallucis brevis; the extrinsics being the tibialis posterior and fibularis longus. Part 4 instructs the exercise and reviews the related literature. Instructions are given for the short-foot, the toe-spread-out, and the heel-raise exercises. The routine may be performed by almost anyone at home and may be adopted into physical therapist practice, with intent to strengthen the foot muscles as an adjunct to almost any protocol of care, but especially for the treatment of hallux valgus deformity. J Orthop Sports Phys Ther 2016;46(7):596 605. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6704. PMID- 27266888 TI - Identification of a novel subgroup 16SrII-U phytoplasma associated with papaya little leaf disease. AB - Papaya is an important fruit crop cultivated in tropical and subtropical regions. Papaya little leaf (PLL) disease was observed in China. The phytoplasma 16S rRNA gene was detected from symptomatic papaya trees via PCR using phytoplasma universal primers P1/P7 followed by R16F2n/R16R2. No amplification products were obtained from templates of asymptomatic papaya trees. These results indicated a direct association between phytoplasma infection and PLL disease. Comparative and phylogenetic analyses of 16S rRNA gene sequences indicated that the papaya infecting phytoplasmas under study belonged to the peanut witches' broom phytoplasma group (16SrII). Genotyping through use of computer-simulated RFLP analysis of 16S rRNA genes and coefficients of RFLP pattern similarities (0.97) reveal that the PLL phytoplasma was placed in a new subgroup. In this article, we describe the molecular characterization of a new phytoplasma associated with PLL disease and propose that the PLL phytoplasma be considered as a novel subgroup, 16SrII-U. PMID- 27266889 TI - An interview with Alfredo Falcone and Lisa Salvatore: RECOURSE and trifluridine/tipiracil in metastatic colorectal cancer. AB - Professor Alfredo Falcone and Dr Lisa Salvatore speak to Roshaine Gunawardana, Managing Commissioning Editor: Professor Alfredo Falcone is the Director of the Department of Oncology and the Specialization School at the University Hospital of Pisa, Italy. He trained in Pisa and Genoa, Italy, and has held major positions in Italian oncology since 2000. He currently has more than 300 publications, including papers in peer-reviewed international and national journals, book chapters, and more than 600 abstracts of presentations to international and national conferences. The majority of his papers regard clinical and translational research, with a particular focus on metastatic colorectal cancer. Dr Lisa Salvatore is a medical oncologist in the Department of Translational Research and New Technologies in Medicine and Surgery at the University of Pisa. She has been an author on about 40 publications in major peer-reviewed publications and has made numerous presentations in national and international conferences. Her main interest is focused on clinical and translational research in metastatic colorectal cancer. PMID- 27266890 TI - Use of Evidence in the Implementation of Social Programs: A Qualitative Study from Chile. AB - Through this qualitative, empirical study the authors aim to explore and describe the sources of knowledge that are used to guide intervention practice by social workers in Chile. Particular attention was paid to factors that may facilitate or hinder the use of research-based evidence to guide social interventions design, implementation, and outcome evaluation. In order to explore these issues, 25 semi structured interviews with social workers from Chilean social service non-profit organizations were conducted. The main findings suggest that social workers do not use research-based evidence to support their social interventions due to various personal organizational constraints (e.g., lack of time, lack of access to resources for disseminating evidence, lack of English command). In addition, no evaluation processes of social programs which will support evidence-based effectiveness could be found. One key barrier to support use of evidence and evidence production may be related to the fact that most non-governmental organizations maintain a hierarchical and vertical relationship with state agencies (program design, oversight, and funding) for social program development. PMID- 27266891 TI - New adduct of abietane-type diterpene from Salvia leriifolia Benth. AB - A new adduct of abietane-type diterpene, salvialeriicone (1), was isolated from Salvia leriifolia Benth., along with a new chemical entity nor-abietane diterpene, 2-isopropyl-8,8-dimethyl-7,8-dihydrophenanthrene-1,4,5(6H)-trione (2). Their structures were determined using mass spectrometry, and 1D- and 2D-NMR spectroscopy. PMID- 27266893 TI - Acute effects of 3G mobile phone radiations on frontal haemodynamics during a cognitive task in teenagers and possible protective value of Om chanting. AB - Mobile phone induced electromagnetic field (MPEMF) as well as chanting of Vedic mantra 'OM' has been shown to affect cognition and brain haemodynamics, but findings are still inconclusive. Twenty right-handed healthy teenagers (eight males and 12 females) in the age range of 18.25 +/- 0.44 years were randomly divided into four groups: (1) MPONOM (mobile phone 'ON' followed by 'OM' chanting); (2) MPOFOM (mobile phone 'OFF' followed by 'OM' chanting); (3) MPONSS (mobile phone 'ON' followed by 'SS' chanting); and (4) MPOFSS (mobile phone 'OFF' followed by 'SS' chanting). Brain haemodynamics during Stroop task were recorded using a 64-channel fNIRS device at three points of time: (1) baseline, (2) after 30 min of MPON/OF exposure, and (3) after 5 min of OM/SS chanting. RM-ANOVA was applied to perform within- and between-group comparisons, respectively. Between group analysis revealed that total scores on incongruent Stroop task were significantly better after OM as compared to SS chanting (MPOFOM vs MPOFSS), pre frontal activation was significantly lesser after OM as compared to SS chanting in channel 13. There was no significant difference between MPON and MPOF conditions for Stroop performance, as well as brain haemodynamics. These findings need confirmation through a larger trial in future. PMID- 27266892 TI - Thyrotropin Receptor Antibody Levels at Diagnosis and After Thionamide Course Predict Graves' Disease Relapse. AB - BACKGROUND: Thionamides are associated with a high risk of recurrence following cessation. Thyrotropin receptor-stimulating antibody (TRAb) levels at diagnosis and/or after thionamides may be biomarkers of this risk. This study assesses the natural history of Graves' thyrotoxicosis following thionamide withdrawal and factors that predict recurrence, particularly TRAb levels at diagnosis and cessation. METHODS: An observational study was conducted of patients with a first presentation of Graves' disease, who were prescribed (and completed) a course of primary thionamide treatment (n = 266) in a university teaching hospital endocrine clinic. Recurrence rates over four years and factors predictive of recurrent thyrotoxicosis were assessed. RESULTS: The relapse rate was 31% at one year and 70% at four years. Younger age (39 years [range 30-49 years] vs. 47 years [range 37-53 years]; p = 0.011), higher TRAb levels at diagnosis (8.8 IU/L [range 5.3-17.0 IU/L] vs. 5.7 IU/L [range 4.1-9.1 IU/L]; p = 0.003), and higher TRAb levels at cessation of therapy (1.2 IU/L [range 0-2.3 IU/L] vs. <0.9 IU/L [range 0-1.3 IU/L]; p = 0.003) were associated with a higher risk of relapse. By four years, cessation TRAb <0.9 IU/L was associated with a 58% risk of recurrence compared with 82% with TRAb >1.5 IU/L (p = 0.001). TRAb at diagnosis >12 IU/L was associated with an 84% risk of recurrence over four years compared with 57% with TRAbs <5 IU/L (p = 0.002). CONCLUSION: High TRAb at diagnosis and/or positive TRAb at cessation of therapy suggest a high likelihood of relapse, mostly within the first two years. They stratify patients likely to need definitive therapy (radioiodine or surgery). PMID- 27266894 TI - Bacteria-Affinity 3D Macroporous Graphene/MWCNTs/Fe3O4 Foams for High-Performance Microbial Fuel Cells. AB - Promoting the performance of microbial fuel cells (MFCs) relies heavily on the structure design and composition tailoring of electrode materials. In this work, three-dimensional (3D) macroporous graphene foams incorporated with intercalated spacer of multiwalled carbon nanotubes (MWCNTs) and bacterial anchor of Fe3O4 nanospheres (named as G/MWCNTs/Fe3O4 foams) were first synthesized and used as anodes for Shewanella-inoculated microbial fuel cells (MFCs). Thanks to the macroporous structure of 3D graphene foams, the expanded electrode surface by MWCNTs spacing, as well as the high affinity of Fe3O4 nanospheres toward Shewanella oneidensis MR-1, the anode exhibited high bacterial loading capability. In addition to spacing graphene nanosheets for accommodating bacterial cells, MWCNTs paved a smoother way for electron transport in the electrode substrate of MFCs. Meanwhile, the embedded bioaffinity Fe3O4 nanospheres capable of preserving the bacterial metabolic activity provided guarantee for the long-term durability of the MFCs. With these merits, the constructed MFC possessed significantly higher power output and stronger stability than that with conventional graphite rod anode. PMID- 27266895 TI - Measuring the quality of motivational interviewing in primary health care encounters: The development and validation of the motivational interviewing assessment scale (MIAS). AB - BACKGROUND: Motivational interviewing (MI) is a collaborative, goal-oriented method to help patients change behaviour. Tools that are often used to measure MI are the motivational interviewing skills code' (MISC), the 'motivational interviewing treatment integrity' (MITI) and the 'behaviour change counselling index' (BECCI). The first two instruments have not been designed to be used in primary healthcare (PHC) settings. The BECCI actually is time-consuming. The motivational interviewing assessment scale (MIAS, 'EVEM' in Spanish) was developed to measure MI in PHC encounters as an alternative to the previous instruments. OBJECTIVES: To validate MIAS as an instrument to assess the quality of MI in PHC settings. METHODS: (a) DEVELOPMENT: Sixteen experts in MI participated in the design, face and consensus validity, using a Delphi-type methodology. (b) VALIDATION: SETTING: 27 PHC centres located in Spain. SUBJECTS: four experts in MI tested its psychometric properties with 332 video recordings coming from the Dislip-EM study (consultations provided by 37 practitioners). MEASUREMENTS: dimensionality, internal consistency, reliability (intra-class correlation coefficient-ICC), sensitivity to change and convergent validity with the BECCI scale. RESULTS: A 14-item scale was obtained after the validation process. Factor analysis: two factors explained 76.6% of the total variance. Internal consistency, alpha = 0.99. Reliability: intra-rater ICC = 0.96; inter rater ICC = 0.97. Sensitivity to change: means before and after training were 23.63 versus 38.57 (P < 0.001). Spearman's coefficient between the MIAS and the BECCI scale was 0.98 (P < 0.001). CONCLUSION: The MIAS is a consistent and reliable instrument to assess the use of MI in PHC settings. [Box: see text]. PMID- 27266896 TI - Water Dissociation upon Adsorption onto Free Iron Clusters Is Size Dependent. AB - Cationic iron clusters, produced through laser ablation and subsequently complexed with a water molecule Fen(+)-H2O (n = 6-15) are mass-selectively investigated via infrared multiple photon dissociation (IR-MPD) spectroscopy in the 300-1700 cm(-1) spectral range. The experimental data are complemented by density functional theory calculations at the OPBE/TZP level for the Fe13(+)-H2O system. The observed spectra can be explained by a mixture of clusters where for a majority water is adsorbed molecularly but for a small but significant fraction also dissociation of water molecules occurs. The bands observed at frequencies 300-700 cm(-1) exhibit regular, size-dependent frequency shifts, showing that (a) dissociation takes places on all cluster sizes and (b) the interaction of water with the cluster surface is not influenced much by the particular cluster structure. The intensity evolution of the absorption bands suggests that dissociation is increasingly probable for larger cluster sizes. PMID- 27266897 TI - Preparation of nitrate-selective porous magnetic resin and assessment of its performance in removing nitrate from groundwater. AB - Nitrate-selective, porous magnetic anion-exchange resin (NS-PMAER) with enhanced affinity and higher selectivity for nitrate was synthesized, characterized and its performance in nitrate removal was investigated. The results show that NS PMAER consists of spherical particles with an average size of 200 MUm. It has mean pore diameter, total pore volume, and BET specific surface area of 21.38 nm, 0.3605 cm3/g, and 67.455 m2/g, respectively. The specific saturation magnetization of NS-PMAER was about 10.79 emu/g. Fourier transform infrared spectrometer (FTIR) and X-ray photoelectron spectroscopy (XPS) results indicate that NS-PMAER has selectivity for nitrate higher than that of MIEX(r) resin; its coefficients of selectivity toward nitrate for nitrate and sulfate are 20.978 and 6.769, respectively, higher than those of MIEX(r) resin (1.256 and 4.342, respectively). Its working exchange capacity was 72.41 mg/mL. Column-exchange experiments' results suggest that it could be easily regenerated using 1.5 mol/L sodium chloride solution for a contact time of 30 min. Its recovery rate stayed at > 95% even after five rounds of recycling. Results of the pilot test indicate that NS-PMAER could effectively remove nitrate in groundwater, and ensure that nitrate concentrations of effluent to meet the guideline limit for drinking water by the World Health Organization. PMID- 27266898 TI - [Spontaneous regression of a pulmonary adenocarcinoma]. PMID- 27266899 TI - [Review of reimbursement for instrumental techniques used for assisted coughing and thoracic expansion. A French National Health Authority assessment (HAS)]. AB - INTRODUCTION: In France, children with neuromuscular diseases and patients with traumatic spinal cord injuries receive reimbursement for home use of intermittent positive-pressure breathing and mechanical in-exsufflators devices. The aim of the study was to update the indications for reimbursement for these both devices. METHODS: A literature review was conducted with several bibliographic databases using the main keywords: intermittent positive-pressure breathing, mechanical insufflation, mechanically-assisted cough, airway clearance. Nine health professionals were interviewed during two meetings. One health professional was interviewed via a questionnaire. An estimation of the population treated with in exsufflators or intermittent positive-pressure breathing was undertaken from consumer data available for all beneficiaries of the health insurance system. STATE OF THE ART: The review identified 111 references which included 14 clinical practice guidelines, two systematic reviews and one randomized controlled trial. Some clinical data were available. Clinical practice guidelines were in favor of using intermittent positive-pressure breathing and in-exsufflators in patients with neuromuscular disease and spinal cord injuries. The healthcare professionals emphasized the need to reimburse the patient for home use of intermittent positive-pressure breathing and in-exsufflators. The patient population treated in the identified clinical situations was estimated at 3100 per year. CONCLUSIONS: Despite the low level of evidence and after interviewing healthcare professionals, the Haute Autorite de sante (HAS) recommended reimbursement of the costs of in-exsufflators (assisted coughing) and intermittent positive-pressure breathing (thoracic expansion) devices in adults and children with neurological and neuromuscular disease, including spinal cord injury. PMID- 27266900 TI - [Bevacizumab in combination with first-line treatment for metastatic non-small cell lung cancer in clinical practice. Results of the EOLE study]. AB - INTRODUCTION: The EOLE cohort aimed to describe, in routine clinical practice, the characteristics and management of patients receiving bevacizumab in combination with first-line metastatic chemotherapy for advanced metastatic or recurrent non squamous non-small cell lung cancer (nsNSCLC), as well as its efficacy and safety. METHODS: A total of 423 patients were enrolled in this prospective, national, multicenter study. Data were collected every 3 months over an 18-month period. RESULTS: Amongst the 407 patients analyzed (mean age 60+/-10 years, male 68%, ECOG-PS<=1 88%, smokers or former smokers 87%, cardiovascular comorbidities 40%), all except for 2 patients received bevacizumab (7.5 or 15mg/kg/3 weeks in 99% of patients) in combination with doublet chemotherapy. A total of 160 (60%) patients who completed induction received bevacizumab maintenance therapy. Median progression-free survival was 6.9 months (95% CI=[6.0 7.5]). Median overall survival (12.8 months [10.4-14.7]) was longer in patients with ECOG-PS<=1 (14.4 months [12.3-15.9] versus 4.9 months [3.4-8.3] if ECOG PS=2). A total of 131 (32%) patients experienced at least one serious adverse event (SAE), and 51 (12%) at least one bevacizumab-related SAE. CONCLUSION: EOLE confirms the efficacy and safety of bevacizumab in aNSCLC patients, in current medical practice. PMID- 27266901 TI - [Molecular epidemiology of the lung cancer]. AB - Lung cancers are common malignancies, which have a very poor prognosis. These are the leading cause of cancer deaths in France and worldwide. Behind this unfavourable prognosis hides many disparities according to age, sex, social level and exposure to risk factors. The detection of the genetic abnormalities, which drive carcinogenesis has totally changed the therapeutic approach. Tumours are now classified according to their molecular profile which is itself associated with new demographic data. We here review the most recent data on this topic. PMID- 27266902 TI - In vitro performance investigation of bioresorbable scaffolds - Standard tests for vascular stents and beyond. AB - BACKGROUND/PURPOSE: Biodegradable polymers are the main materials for coronary scaffolds. Magnesium has been investigated as a potential alternative and was successfully tested in human clinical trials. However, it is still challenging to achieve mechanical parameters comparative to permanent bare metal (BMS) and drug eluting stents (DES). As such, in vitro tests are required to assess mechanical parameters correlated to the safety and efficacy of the device. METHODS/MATERIALS: In vitro bench tests evaluate scaffold profiles, length, deliverability, expansion behavior including acute elastic and time-dependent recoil, bending stiffness and radial strength. The Absorb GT1 (Abbott Vascular, Temecula, CA), DESolve (Elixir Medical Corporation, Sunnyvale, CA) and the Magmaris (BIOTRONIK AG, Bulach, Switzerland) that was previously tested in the BIOSOLVE II study, were tested. RESULTS: Crimped profiles were 1.38+/-0.01mm (Absorb GT1), 1.39+/-0.01mm (DESolve) and 1.44+/-0.00mm (Magmaris) enabling 6F compatibility. Trackability was measured depending on stiffness and force transmission (pushability). Acute elastic recoil was measured at free expansion and within a mock vessel, respectively, yielding results of 5.86+/-0.76 and 5.22+/-0.38% (Absorb), 7.85+/-3.45 and 9.42+/-0.21% (DESolve) and 5.57+/-0.72 and 4.94+/-0.31% (Magmaris). Time-dependent recoil (after 1h) was observed for the Absorb and DESolve scaffolds but not for the Magmaris. The self-correcting wall apposition behavior of the DESolve did not prevent time-dependent recoil under vessel loading. CONCLUSIONS: The results of the suggested test methods allow assessment of technical feasibility based on objective mechanical data and highlight the main differences between polymeric and metallic bioresorbable scaffolds. PMID- 27266904 TI - Incidence of venous thromboembolism in patients with diffuse large B-cell lymphoma. AB - Venous thromboembolism (VTE) in patients with diffuse large B-cell lymphoma (DLBCL) is an important complication. We aimed to asses the risk of VTE and the quality of VTE discharge diagnosis in a cohort of DLBCL patients. Objective confirmed VTE events during two years of follow-up were identified by the review of medical records of consecutive patients with DLBCL at Aalborg University Hospital from 2007 until 2013. Information on baseline disease stage, lifestyle factors, and anticoagulant therapy were registered. Cox regression was used to assess VTE risk factors. The data quality on VTE discharge diagnosis was evaluated by comparing data on VTE discharge diagnosis from the Danish National Registry of Patients with information from the medical records. Eleven percent of patients were diagnosed with VTE. Prior VTE, performance status, and Ann Arbor stage were associated with VTE. The positive predictive value of a VTE discharge diagnosis was 85% and the sensitivity 53%. PMID- 27266903 TI - Serum Levels of Persistent Organic Pollutants and Insulin Secretion among Children Age 7-9 Years: A Prospective Cohort Study. AB - BACKGROUND: Persistent organic pollutants (POPs) are endocrine disruptors and have been suggested as possible risk factors for diabetes. Few studies have been performed to investigate this association among children. OBJECTIVES: In this study, we prospectively examined the relationship between the serum concentration of POPs and glucose metabolism in children. METHODS: Data were collected from the Ewha Birth & Growth Cohort Study, an ongoing birth cohort study initially constructed between 2001 and 2006. In 2010-2012, the POP concentration was measured in serum from a total of 214 children, 7-9 years of age. Using fasting glucose and insulin measurements at both baseline and the second year of follow up, the homeostatic model assessment of beta-cell function (HOMA-beta) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Multiple linear regression analysis and a linear mixed-effects model were used to determine the relationship between POP tertiles and metabolic biomarkers. RESULTS: Compared with the lowest tertile of total marker PCBs, participants in the third tertile had decreased HOMA-beta values, after adjustment for age, sex, body mass index z-score, mother's education, ponderal index, and history of breastfeeding (-18.94%; 95% CI: -32.97%, -1.98%). In a linear mixed model, the HOMA-beta values were still lower in subjects in the highest compared with the lowest tertile of total PCBs at the 2-year follow-up period (108.3 vs. 135.0, respectively). CONCLUSION: The results of the study suggested that exposure to POPs among children might affect insulin secretory function, which could lead to an increased risk of developing diabetes. Citation: Park SH, Ha EH, Hong YS, Park H. 2016. Serum levels of persistent organic pollutants and insulin secretion among children age 7-9 years: a prospective cohort study. Environ Health Perspect 124:1924-1930; http://dx.doi.org/10.1289/EHP147. PMID- 27266914 TI - Total Synthesis of Thailanstatin A. AB - The total synthesis of the spliceosome inhibitor thailanstatin A has been achieved in a longest linear sequence of nine steps from readily available starting materials. A key feature of the developed synthetic strategy is the implementation of a unique, biomimetic asymmetric intramolecular oxa-Michael reaction/hydrogenation sequence that allows diastereodivergent access to highly functionalized tetrahydropyrans, which can be used for the synthesis of designed analogues of this bioactive molecule. PMID- 27266916 TI - Ketyl Radical Formation via Proton-Coupled Electron Transfer in an Aqueous Solution versus Hydrogen Atom Transfer in Isopropanol after Photoexcitation of Aromatic Carbonyl Compounds. AB - The excited npi* and pipi* triplets of two benzophenone (BP) and two anthraquinone (AQ) derivatives have been observed in acetonitrile, isopropanol, and mixed aqueous solutions using time-resolved resonance Raman spectroscopic and nanosecond transient absorption experiments. These experimental results, combined with results from density functional theory calculations, reveal the effects of solvent and substituents on the properties, relative energies, and chemical reactivities of the npi* and pipi* triplets. The triplet npi* configuration was found to act as the reactive species for a subsequent hydrogen atom transfer reaction to produce a ketyl radical intermediate in the isopropanol solvent, while the triplet pipi* undergoes a proton-coupled electron transfer (PCET) in aqueous solutions to produce a ketyl radical intermediate. This PCET reaction, which occurs via a concerted proton transfer (to the excited carbonyl group) and electron transfer (to the excited phenyl ring), can account for the experimental observation by several different research groups over the past 40 years of the formation of ketyl radicals after photolysis of a number of BP and AQ derivatives in aqueous solutions, although water is considered to be a relatively "inert" hydrogen-donor solvent. PMID- 27266917 TI - Letter. PMID- 27266915 TI - Estradiol impacts the endocannabinoid system in female rats to influence behavioral and structural responses to cocaine. AB - Compared with men, women show enhanced responses to drugs of abuse, and consequently are thought to be more vulnerable to addiction. The ovarian hormone estradiol has emerged as a key facilitator in the heightened development of addiction in females. These actions of estradiol appear mediated by estrogen receptor (ER) activation of metabotropic glutamate receptor type 5 (mGluR5). However, the downstream effectors of this ER/mGluR5 signaling pathway are unknown. Here we investigate whether cannabinoid 1 receptor (CB1R) activation is a part of the mechanism whereby estradiol influences behavioral and synaptic correlates of addiction. Following repeated cocaine administration, estradiol treated ovariectomized rats exhibited both sensitized locomotor responses and decreases in the dendritic spine density of nucleus accumbens core medium-spiny neurons in comparison to oil-treated controls. Both effects of estradiol were blocked by AM251, a CB1R inverse agonist. These results indicate that part of the signaling mechanism through which estradiol impacts behavioral and synaptic correlates of addiction in female rats requires activation of CB1Rs. PMID- 27266943 TI - Free serum valproate concentration more reliable than total concentration in critically ill patients. PMID- 27266918 TI - Serum apelin is associated with affective disorders in peritoneal dialysis patients. AB - OBJECTIVE: Depression and anxiety are prevalent affective disorders in peritoneal dialysis (PD) patients. Recent research has proposed a potential role of apelinergic system in pathogenesis of depression. The present study aimed to evaluate the frequency of depression and anxiety and their potential relation with serum apelin levels among PD patients. METHODS: A total of 40 PD patients were enrolled into the study. Depressive symptoms and anxiety were assessed with the Beck's Depression Inventory and the Beck's Anxiety Inventory. Serum apelin-12 levels were measured by immunoenzymatic assays using commercially available ELISA kit for standard human apelin. RESULTS: Of the patients, 16 (40%) had depression, 20 (50%) had anxiety. The patients with depression and anxiety had a significantly longer time on dialysis (p < 0.001 for both), significantly higher serum apelin (p < 0.001 for both) and C-reactive protein levels (p < 0.001 for both) than those without depression and anxiety. In multivariate analysis, serum apelin was the only parameter associated independently with depression and anxiety scores. CONCLUSIONS: A substantial number of PD patients had depression and anxiety. Increased levels of serum apelin may constitute a significant independent predictor of development of depression and anxiety in PD patients. PMID- 27266944 TI - Persistent nodal histoplasmosis in nuclear factor kappa B essential modulator deficiency: Report of a case and review of infection in primary immunodeficiencies. PMID- 27266945 TI - A way out of the dismal arithmetic of hepatitis C treatment. PMID- 27266946 TI - It's time to end insurance restrictions on life-saving hepatitis C treatments. PMID- 27266947 TI - Does patient cost sharing for HCV drugs make sense? PMID- 27266948 TI - Sofosbuvir initial therapy abandonment and manufacturer coupons in a commercially insured population. AB - OBJECTIVES: To describe rates of sofosbuvir initial medication adherence as a function of the insurer-required member cost (ie, out-of-pocket cost) and to determine how manufacturer coupons affect insurer-required member cost. STUDY DESIGN: Observational cross-sectional analysis. METHODS: Administrative pharmacy claims data from 13 million commercially insured members were used to identify sofosbuvir new starts between January 2014 and September 2014. Members were categorized as either sofosbuvir initial adherence or as abandoning therapy. A multivariate logistic regression model adjusting for sociodemographic characteristics, severity of illness, and total drug costs (health insurer plus member amount) for non-sofosbuvir pharmacy claims in 2014 was used to evaluate the association between insurer-required member cost and initial medication adherence. In a sub-analysis, sofosbuvir index claims with coupon data available were analyzed to determine how coupon use impacted insurer-required member cost. RESULTS: A total of 67.3% of members had a pre-coupon member cost of < $250 for their index sofosbuvir claim. Just 201 (5.0%) members were exposed to a member cost of more than $10,000. The logistic regression model demonstrated an association between member cost and abandonment starting at $2500 to < $5000 (odds ratio: 1.9; 95% CI, 1.01-3.43; P = .0393). The average member sofosbuvir index claim cost was $1349 before coupon was applied, and $28 after. Overall, coupons offset the member amounts paid by 98%: $771,593 of the $787,860 member cost requested by the insurer. CONCLUSIONS: These findings indicate that a 30-day supply sofosbuvir member cost of > $2500 was associated with increased initial therapy abandonment, and that manufacturer coupons substantially reduced sofosbuvir insurer-required member cost. Insurers and policy makers should consider the impact of member cost on medication adherence and the impact coupons have on the actual member cost. PMID- 27266950 TI - Real-world outcomes of ledipasvir/sofosbuvir in treatment-naive patients with hepatitis C. AB - OBJECTIVES: Studies of hepatitis C virus (HCV) regimens have documented substantially reduced effectiveness in sustained virologic response (SVR) in the context of real-world clinical practice compared with clinical trials. Real-world and clinical trial SVR and cost-per-SVR data have not been reported for the all oral, peginterferon-free and ribavirin (RBV)-free ledipasvir/sofosbuvir (LDV/SOF) regimen. Our objective was to compare the rates of SVR achievement and cost per SVR between pooled data from clinical studies of LDV/SOF and from real-world clinical practice. METHODS: Data were derived from the Hepatitis C Therapeutic Registry and Research Network (HCV-TARGET), a real-world, multicenter, prospective, observational study; and from the TRIO Network, a retrospective database of HCV-treated patients. The 1-year cost per SVR was calculated as the total cost of an SVR ([cost of treatment regimen, adverse events, and monitoring costs] per SVR) during the first year of treatment. RESULTS: After 12 weeks, the SVR rates obtained in real-world studies ranged from 94% to 98%, comparing favorably with the SVRs achieved in the ION-1 and ION-3 trials (94% and 95%-99% with 8 and 12 weeks of RBV-free therapy, respectively). A single SVR, on average, cost $84,989 among patients enrolled in the ION-3 trial, with higher costs ($101,204) among patients with compensated cirrhosis compared with noncirrhotic patients ($81,668). In the pooled TARGET/TRIO population, the average cost of an SVR was $84,770, with costs of $101,380 and $81,368 in patients with compensated cirrhosis and patients without cirrhosis, respectively. CONCLUSIONS: Unlike the results obtained with prior HCV regimens, this study suggests that similar SVR rates are achieved with LDV/SOF in clinical trial-based studies and real-world studies. Further, achieving an SVR in real-world clinical practice was not associated with excess costs. PMID- 27266949 TI - Improving HCV cure rates in HIV-coinfected patients - a real-world perspective. AB - OBJECTIVES: To study rates and predictors of hepatitis C virus (HCV) cure among human immunodeficiency virus (HIV)/HCV-coinfected patients, and then to evaluate the effect of attendance at clinic visits on HCV cure. METHODS: Retrospective cohort study of adult HIV/HCV-coinfected patients who initiated and completed treatment for HCV with direct-acting antivirals (DAAs) between January 1, 2014, and June 30, 2015. RESULTS: Eighty-four participants reported completing treatment. The median age was 58 years (interquartile ratio, 50-66); 88% were male and 50% were black. One-third were cirrhotic and half were HCV-treatment experienced. The most commonly used regimen was sofosbuvir/ledipasvir (40%) followed by simeprevir/sofosbuvir (30%). Cure was achieved in 83.3%, 11.9% relapsed, and 2.3% experienced virological breakthrough. Two patients (2.3%) did not complete treatment based on pill counts and follow-up visit documentation. In multivariable analysis, cure was associated with attendance at follow-up clinic visits (odds ratio [OR], 9.0; 95% CI, 2.91-163) and with use of an integrase based HIV regimen versus other non-integrase regimens, such as non-nucleoside analogues or protease inhibitors (OR, 6.22; 95% CI 1.81-141). Age, race, genotype, presence of cirrhosis, prior HCV treatment, HCV regimen, and pre treatment CD4 counts were not associated with cure. CONCLUSIONS: Real-world HCV cure rates with DAAs in HCV/HIV coinfection are lower than those seen in clinical trials. Cure is associated with attendance at follow-up clinic visits and with use of an integrase-based HIV regimen. Future studies should evaluate best antiretroviral regimens, predictors of attendance at follow-up visits, impact of different monitoring protocols on medication adherence, and interventions to ensure adequate models of HIV/HCV care. PMID- 27266951 TI - The wider public health value of HCV treatment accrued by liver transplant recipients. AB - OBJECTIVES: Organs for transplantation are scarce, but new medical therapies can prevent organ failure and the need for transplants. We sought to describe the unique value created by treatments that spare organs from failure and thus conserve donated organs for transplant into others, using hepatitis C virus (HCV) as a case study. STUDY DESIGN: Epidemiologic-economic model. METHODS: Using data on trends in chronic liver disease, liver disease progression, and liver transplant allocation models, as well as the effectiveness of new HCV treatments, we estimate the potential effects of systematic HCV screening and treatment on the demand for liver transplants in the United States. We estimate the spillover benefits to patients with all-cause liver disease in terms of increased availability of transplants and life-years gained. RESULTS: We estimated that systematic HCV screening and treatment could spare 10,490 liver transplants to HCV-infected patients from 2015 to 2035. An estimated 7321 transplants would accrue to patients with end-stage liver disease without HCV and 3169 transplants to those with uncured HCV, providing approximately 52,700 and 22,800 additional life-years, respectively. CONCLUSIONS: Treatment advances for HCV have the potential to generate considerable spillover benefits to patients awaiting transplants for non-HCV-mediated liver failure. For other diseases in which organ transplants are in short supply, our study provides a novel pathway by which positive spillovers may accrue from treatments that prevent end-stage organ disease. PMID- 27266952 TI - Coverage for hepatitis C drugs in Medicare Part D. AB - OBJECTIVES: The recent arrival of new hepatitis C virus (HCV) drugs has brought fiscal pressures onto Medicare Part D; spending on HCV drugs in Part D jumped from $283 million in 2013 to $4.5 billion in 2014. We examined the current benefit designs for HCV drugs in Part D plans and analyzed patients' financial burden for those drugs. STUDY DESIGN: A cross-sectional analysis of CMS' July 2015 Part D Plan Formulary File and the Wolters Kluwer Health Medi-Span Electronic Drug File v.2. METHODS: We analyzed the type and amount of cost sharing for HCV drugs and the extent to which plans apply utilization management tools. We then estimated total out-of-pocket spending for beneficiaries to complete a course of treatment. RESULTS: All Part D plans covered at least 1 recently introduced HCV drug, as of July 2015. Nearly all plans charged relatively high coinsurance and required prior authorization for new HCV drugs. For enrollees with no subsidy, the mean out-of-pocket spending needed to complete a course of treatment is substantial, ranging from $6297 to $10,889. For enrollees with a low-income subsidy, out-of-pocket spending varies between $10.80 and $1191. CONCLUSIONS: Under the current Part D benefits, HCV drug users with no subsidy face sizable financial burdens, even with catastrophic coverage and the recent in-gap discount for brand name drugs. As baby boomers-the group most likely to have HCV-join Medicare, efforts should be made to ensure patient access to these needed drugs. PMID- 27266953 TI - Value of expanding HCV screening and treatment policies in the United States. AB - OBJECTIVES: To investigate the value of expanding screening and treatment for hepatitis C virus (HCV) infection in the United States. STUDY DESIGN: Discrete time Markov model. METHODS: We modeled HCV progression and transmission to analyze the costs and benefits of investment in screening and treatment over a 20 year time horizon. Population-level parameters were estimated using National Health and Nutrition Examination Survey data and published literature. We considered 3 screening scenarios that vary in terms of clinical guidelines and physician awareness of guidelines. For each screening scenario, we modeled 3 approaches to treatment, varying the fibrosis stage of treatment initiation. Net social value was the key model outcome, calculated as the value of benefits from improved quality-adjusted survival and reduced transmission minus screening, treatment, and medical costs. RESULTS: Expanded screening policies generated the largest value to society. However, this value is constrained by the availability of treatment to diagnosed patients. Screening all individuals in the population generates $0.68 billion in social value if diagnosed patients are treated in fibrosis stages F3-F4 compared with $824 billion if all diagnosed patients in stages F0-F4 are treated. Moreover, increased screening generates cumulative net social value by year 8 to 9 under expanded treatment policies compared with 20 years if only patients in stages F3-F4 are treated. CONCLUSIONS: Although increasing screening for HCV may generate some value to society, only when paired with expanded access to treatment at earlier disease stages will it produce considerable value. Such a "test and treat" strategy is likely to entail higher short-term costs but also yield the greatest social benefits. PMID- 27266954 TI - Costs and spillover effects of private insurers' coverage of hepatitis C treatment. AB - OBJECTIVES: Hepatitis C virus (HCV) treatment incentives for private payers may be misaligned because payers must bear immediate costs and may not realize long term benefits. However, these benefits may accrue to future payers, including Medicare. We examined how and to what extent private payers' current HCV treatment coverage decisions impact Medicare's and private payers' future costs. STUDY DESIGN: Discrete-time Markov model. METHODS: We modeled HCV disease progression and transmission to simulate the economic and social effects of different private-payer HCV treatment scenarios on Medicare. The model examined differences between a baseline scenario (current practice guidelines) and 2 alternative scenarios that expand treatment coverage. Spillover effects were measured as reduced HCV treatment costs and medical expenditures in Medicare. We calculated the spillover effects and net social value of each scenario (total value of quality-adjusted life-years accrued over time minus cumulative treatment and medical costs). RESULTS: With expanded HCV treatment coverage, private payers experience reduced medical expenditures in the 3-to-5-year time horizon; however, they still face higher treatment costs. Over a 20-year horizon, private payers experience overall savings of $10 billion to $14 billion after treatment costs. The expansion of coverage by private payers generates positive spillover benefits to Medicare of $0.3 billion to $0.7 billion over a 5-year horizon, and $4 billion to $11 billion over a 20-year horizon. CONCLUSIONS: When private payers increase HCV treatment coverage, they may achieve significant savings while inducing spillover benefits to Medicare. Future savings, however, may not motivate immediate treatment investments among private payers who experience high beneficiary turnover. PMID- 27266955 TI - Pharmacogenetics and pharmacogenomics in psoriasis treatment: current challenges and future prospects. AB - INTRODUCTION: Topical, systemic, oral disease modifying, and biologic agents are part of the armamentarium to manage psoriatic disease. The choice of therapy depends upon disease severity, relevant co-morbidities and patient preference. There is great variability in patient response with these agents, and there is still no clear method of selecting the preferred therapeutic agent for efficacy or lack of adverse events. AREAS COVERED: This article will review the pharmacogenetic and pharmacogenomic targets that are currently known with respect to psoriasis vulgaris, and the most frequent co-morbidity of psoriasis, psoriatic arthritis. EXPERT OPINION: Presently, no clinically actionable biomarker exists for any therapeutic agent used to treat psoriasis or psoriatic arthritis. The lack of validated outcome measures and conflicting results of open-label studies conducted may be attributed to a multitude of issues that confound discovery. Consequently, studies have been underpowered to identify genes or genetic variants worth translating to clinical practice. In order to achieve a pharmacogenetic/pharmacogenomic signature, improvements in study design of future investigations are required, including carefully designed prospective studies. It is imperative to combine known clinical, serological, and molecular markers with consistent outcomes and an adequate health economic evaluation before they can be adopted widely in clinical practice. PMID- 27266956 TI - Have microfluidics delivered for drug discovery? PMID- 27266957 TI - Metformin is also effective on lactic acidosis-exposed melanoma cells switched to oxidative phosphorylation. AB - Low extracellular pH promotes in melanoma cells a malignant phenotype characterized by an epithelial-to-mesenchymal transition (EMT) program, endowed with mesenchymal markers, high invasiveness and pro-metastatic property. Here, we demonstrate that melanoma cells exposed to an acidic extracellular microenvironment, 6.7+/-0.1, shift to an oxidative phosphorylation (Oxphos) metabolism. Metformin, a biguanide commonly used for type 2 diabetes, inhibited the most relevant features of acid-induced phenotype, including EMT and Oxphos. When we tested effects of lactic acidosis, to verify whether sodium lactate might have additional effects on acidic melanoma cells, we found that EMT and Oxphos also characterized lactic acid-treated cells. An increased level of motility was the only gained property of lactic acidic-exposed melanoma cells. Metformin treatment inhibited both EMT markers and Oxphos and, when its concentration raised to 10 mM, it induced a striking inhibition of proliferation and colony formation of acidic melanoma cells, both grown in protons enriched medium or lactic acidosis. Thus, our study provides the first evidence that metformin may target either proton or lactic acidosis-exposed melanoma cells inhibiting EMT and Oxphox metabolism. These findings disclose a new potential rationale of metformin addition to advanced melanoma therapy, e.g. targeting acidic cell subpopulation. PMID- 27266958 TI - Economic impact of onabotulinumtoxinA for overactive bladder with urinary incontinence in Europe. AB - BACKGROUND: Overactive bladder (OAB) is a common condition that has a significant impact on patients' health-related quality-of-life and is associated with a substantial economic burden to healthcare systems. OnabotulinumtoxinA has a well established efficacy and safety profile as a treatment for OAB; however, the economic impact of using onabotulinumtoxinA has not been well described. METHODS: An economic model was developed to assess the budget impact associated with OAB treatment in France, Germany, Italy, Spain and the UK, using onabotulinumtoxinA alongside best supportive care (BSC)-comprising incontinence pads and/or anticholinergic use and/or clean intermittent catheterisation (CIC)-vs BSC alone. The model time horizon spanned 5 years, and included direct costs associated with treatment, BSC, and adverse events. RESULTS: Per 100,000 patients in each country, the use of onabotulinumtoxinA resulted in estimated cost savings of ?97,200 (Italy), ?71,580 (Spain), and ?19,710 (UK), and cost increases of ?23,840 in France and ?284,760 in Germany, largely due to day-case and inpatient administration, respectively. Projecting these results to the population of individuals aged 18 years and above gave national budget saving estimates of ?9,924,790, ?27,458,290, and ?48,270,760, for the UK, Spain, and Italy, respectively, compared to cost increases of ?12,160,020 and ?196,086,530 for France and Germany, respectively. Anticholinergic treatment and incontinence pads were the largest contributors to overall spending on OAB management when onabotulinumtoxinA use was not increased, and remained so in four of five scenarios where onabotulinumtoxinA use was increased. This decreased resource use was equivalent to cost offsets ranging from ?106,110 to ?176,600 per 100,000 population. CONCLUSIONS: In three of five countries investigated, the use of onabotulinumtoxinA, in addition to BSC, was shown to result in healthcare budget cost savings over 5 years. Scenario analyses showed increased costs in Germany and France were largely attributable to the treatment setting rather than onabotulinumtoxinA acquisition costs. PMID- 27266960 TI - Single-Component Conductors: A Sturdy Electronic Structure Generated by Bulky Substituents. AB - While the introduction of large, bulky substituents such as tert-butyl, -SiMe3, or -Si(isopropyl)3 has been used recently to control the solid state structures and charge mobility of organic semiconductors, this crystal engineering strategy is usually avoided in molecular metals where a maximized overlap is sought. In order to investigate such steric effects in single component conductors, the ethyl group of the known [Au(Et-thiazdt)2] radical complex has been replaced by an isopropyl one to give a novel single component molecular conductor denoted [Au(iPr-thiazdt)2] (iPr-thiazdt: N-isopropyl-1,3-thiazoline-2-thione-4,5 dithiolate). It exhibits a very original stacked structure of crisscross molecules interacting laterally to give a truly three-dimensional network. This system is weakly conducting at ambient pressure (5 S.cm(-1)), and both transport and optical measurements evidence a slowly decreasing energy gap under applied pressure with a regime change around 1.5 GPa. In contrast with other conducting systems amenable to a metallic state under physical or chemical pressure, the Mott insulating state is stable here up to 4 GPa, a consequence of its peculiar electronic structure. PMID- 27266959 TI - The relationship of pro-inflammatory markers to vascular endothelial function after acute stroke. AB - : Purpose/Aim: Data from chronic stroke studies have reported reduced blood flow and vascular endothelial function in the stroke-affected limb. It is unclear whether these differences are present early after stroke. First, we investigated whether vascular endothelial function in the stroke-affected limb would be different from healthy adults. Second, we examined whether between-limb differences in vascular endothelial function existed in the stroke-affected arm compared to the non-affected arm. Last, we tested whether reduced vascular endothelial function was related to pro-inflammatory markers that are present early after stroke. MATERIALS AND METHODS: Vascular endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery within 72 h post stroke. All participants withheld medications from midnight until after the procedure. Ultrasound scans and blood draws for pro-inflammatory markers occurred on the same day between 7:30 am and 9:00 am. RESULTS: People with acute stroke had significantly lower FMD (4.2% +/- 4.6%) than control participants (8.5% +/- 5.2%, p = 0.037). Stroke participants had between-limb differences in FMD (4.2% +/- 4.6% stroke-affected vs. 5.3% +/- 4.4% non-affected, p = 0.02), whereas, the control participants did not. Of the pro-inflammatory markers, only vascular cell adhesion molecule-1(VCAM-1) had a significant relationship to FMD (stroke affected limb, r = -0.62, p = 0.03; non-affected limb, r = -0.75, p = 0.005), but not tumor necrosis factor alpha nor interleukin-6. CONCLUSIONS: Vascular endothelial function is reduced starting in the early stage of stroke recovery. People with higher levels of VCAM-1 had a lower FMD response. PMID- 27266961 TI - Do the anterior and lateral thalamic nuclei make distinct contributions to spatial representation and memory? AB - The anterior and lateral thalamus has long been considered to play an important role in spatial and mnemonic cognitive functions; however, it remains unclear whether each region makes a unique contribution to spatial information processing. We begin by reviewing evidence from anatomical studies and electrophysiological recordings which suggest that at least one of the functions of the anterior thalamus is to guide spatial orientation in relation to a global or distal spatial framework, while the lateral thalamus serves to guide behavior in relation to a local or proximal framework. We conclude by reviewing experimental work using targeted manipulations (lesion or neuronal silencing) of thalamic nuclei during spatial behavior and single-unit recordings from neuronal representations of space. Our summary of this literature suggests that although the evidence strongly supports a working model of spatial information processing involving the anterior thalamus, research regarding the role of the lateral thalamus is limited and requires further attention. We therefore identify a number of major gaps in this research and suggest avenues of future study that could potentially solidify our understanding of the relative roles of anterior and lateral thalamic regions in spatial representation and memory. PMID- 27266962 TI - Pilot Feasibility Study of an Educational Intervention in Women With Gestational Diabetes. AB - OBJECTIVES: To pilot test the feasibility of an educational intervention, Start Understanding Gestational Diabetes and Risk of Developing Type 2 Diabetes (SUGAR), in women with gestational diabetes mellitus (GDM). DESIGN: A pretest posttest, two-group study design. SETTING: Three obstetrics and gynecology offices in the southeastern United States. PARTICIPANTS: Twenty-three women with a first-time diagnosis of GDM. METHODS: Women diagnosed with GDM were recruited and placed in a control group or educational intervention group. Women completed six self-report, standardized questionnaires at baseline (third trimester) and posttest (6-8 weeks postpartum). Women in the intervention group (n = 18) received the SUGAR educational intervention after the baseline data collection with a booster session at 2 to 4 weeks postpartum. Women in the control group (n = 5) received an attention control treatment. RESULTS: Study participants had obesity, and most had a family history of type 2 diabetes mellitus. The attrition rate was low (n = 2; 8%). The educational intervention significantly increased diabetes mellitus knowledge for women in the SUGAR group. In addition, 39% of participants received the recommended postpartum glucose screening. CONCLUSION: Although the effect of the SUGAR intervention with a small sample was not expected to produce statistically significant changes, we add our pilot study to the limited research of diabetes mellitus preventative care for women with GDM and provide preliminary findings to develop meaningful education and support for women diagnosed with GDM. Future researchers need to focus on prevention programs that center on self-efficacy, postpartum glucose screening, and adoption of healthy lifestyle behaviors. PMID- 27266963 TI - A Comparison of Maternal and Paternal Experiences of Becoming Parents of a Very Preterm Infant. AB - OBJECTIVE: To compare maternal and paternal experiences of very preterm (VPT) birth (gestational age < 32 weeks) and the NICU stay. DESIGN: Qualitative study. SETTING: Data collection took place at parents' homes 3 to 6 months after NICU discharge. PARTICIPANTS: Ten parental couples participated in the study (20 parents). All VPT infants were healthy, without any neonatal or postnatal complications or injuries. METHODS: Computer-assisted content analysis was used to highlight thematic clusters from parents' narratives, which were labeled through qualitative interpretation. RESULTS: Two main dimensions (Adjustment Process to Preterm Birth and Parental Role Assumption) and three main thematic clusters (Facing the Unexpected, Learning to Parent, and Finally Back Home) described the parental experience. Mothers focused mostly on the Finally Back Home cluster, which was characterized by moderate levels of adjustment to preterm birth and by awareness of their own maternal roles. Fathers focused mostly on the Learning to Parent cluster, which was characterized by low to moderate levels of adjustment to preterm birth and by a limited assumption of paternal role. CONCLUSION: To our knowledge, this study is unique in that we compared mothers and fathers who experienced the VPT births of their infants and described their experiences of the NICU stay. We found that the VPT birth experience for parents involves a dynamic adjustment. Differences in maternal and paternal experiences may indicate the need for tailored supportive interventions in the NICU. PMID- 27266964 TI - A Child with Severe Developmental Delay and Growth Retardation. PMID- 27266966 TI - Cellulitis-Like Lesions: An Unusual Manifestation of a Parvovirus B19 Infection. PMID- 27266965 TI - The Role of Nutrition in Brain Development: The Golden Opportunity of the "First 1000 Days". PMID- 27266967 TI - Memory performance is related to the cortisol awakening response in older people, but not to the diurnal cortisol slope. AB - There are large individual differences in age-related cognitive decline. Hypothalamic-pituitary-adrenal axis (HPA-axis) functioning has been suggested as one of the mechanisms underlying these differences. This study aimed to investigate the relationships between the diurnal cortisol cycle, measured as the cortisol awakening response (CAR), and the diurnal cortisol slope (DCS) and the memory performance of healthy older people. To do so, we assessed the verbal, visual, and working memory performance of 64 participants (32 men) from 57 to 76 years old who also provided 14 saliva samples on two consecutive weekdays to determine their diurnal cortisol cycle. The CAR was linearly and negatively associated with verbal (significantly) and visual (marginally) memory domains, but not with working memory. Sex did not moderate these relationships. Furthermore, no associations were found between the DCS and any of the three memory domains assessed. Our results indicate that the two components of the diurnal cortisol cycle have different relationships with memory performance, with the CAR being more relevant than DCS in understanding the link from HPA-axis activity and regulation to different types of memory. These results suggest that the CAR is related to memory domains dependent on hippocampal functioning (i.e., declarative memory), but not to those that are more dependent on prefrontal cortex functioning (i.e., working memory). PMID- 27266970 TI - Cell reprogramming during regeneration in Drosophila: transgression of compartment boundaries. AB - We discuss recent work about cellular reprogramming during regeneration of the imaginal discs of Drosophila. These contain various lineage blocks, compartments, which express distinct genetic programmes. It has been found that after massive damage to a compartment cells from a neighbour compartment can transgress the compartment border and contribute to its regeneration. The transgressing cells are genetically reprogrammed and acquire a new identity, a process facilitated by up regulation of the JNK pathway and transient loss of epigenetic control by the Pc-G and trx-G genes. The final acquisition of the new identity appears to be mediated by induction by neighbour cells, a phenomenon akin the Community Effect described for the specification of amphibian muscle cells. PMID- 27266968 TI - Examining the concurrent and longitudinal relationship between diurnal cortisol rhythms and conduct problems during childhood. AB - Previous literature indicates that both hypoactivity and hyperactivity of the HPA axis may be related to conduct disorder and externalizing behaviors in young children. Using a longitudinal sample of 283 typically-developing children, the current study examined both the concurrent and the longitudinal association between HPA functioning and externalizing behavior problems, such as conduct problems. Diurnal cortisol rhythms and externalizing problems were assessed at ages 6 and 9. Results suggest that concurrent HPA functioning is not significantly related to externalizing behavior at ages 6 or 9. However, more blunted cortisol rhythms at age 6 (less change across the day from morning to evening) predicted a greater increase in externalizing behavior between age 6 and age 9 than did steeper cortisol rhythms. Further analyses revealed that this association was driven by conduct problems and aggressive behavior, rather than attention problems. The relationship between HPA functioning and subsequent externalizing behavior in children adds to the limited longitudinal work on this topic, suggesting that the association changes over time. These results may serve to clarify the inconsistencies in the cross-sectional literature, particularly with respect to young school-age children. PMID- 27266972 TI - Old questions, new models: unraveling complex organ regeneration with new experimental approaches. AB - How do some animals like crabs, flatworms and salamanders regenerate entire body parts after a severe injury? Which are the mechanisms and how did that regenerative ability evolve over time? The ability to regenerate complex organs is widespread in the animal kingdom, but fundamental, centuries-old questions remain unanswered. Forward genetics approaches that were so successful in probing embryonic development are lacking in most regenerative models, and candidate gene approaches can be biased and misleading. We summarize recent progress in establishing new genetic tools and approaches to study regeneration and provide a personal perspective on the feasibility and value of establishing such tools, based on our experience with a new experimental model, the crustacean Parhyale hawaiensis. PMID- 27266969 TI - Regeneration of pancreatic insulin-producing cells by in situ adaptive cell conversion. AB - The impaired ability to produce or respond to insulin, a hormone synthetized by the pancreatic beta-cells, leads to diabetes. There is an excruciating need of finding new approaches to protect or restore these cells once they are lost. Replacement and ex vivo directed reprogramming methods have an undeniable therapeutic potential, yet they exhibit crucial flaws. The in vivo conversion of adult cells to functional insulin-producing cells is a promising alternative for regenerative treatments in diabetes. The stunning natural transdifferentiation potential of the adult endocrine pancreas was recently uncovered. Modulating molecular targets involved in beta-cell fate maintenance or in general differentiation mechanisms can further potentiate this intrinsic cell plasticity, which leads to insulin production reconstitution. PMID- 27266973 TI - Insights into sensory hair cell regeneration from the zebrafish lateral line. AB - Loss of mechanosensory hair cells in the inner ear leads to loss of hearing. In humans this results in permanent deafness, as mammals are largely unable to regenerate hair cells. In contrast, zebrafish robustly regenerate hair cells in the sensory lateral line and ear and recent gene expression and time-lapse analyses of cell behaviors at the single cell level have greatly advanced our understanding of the mechanisms responsible for hair cell regeneration. In the lateral line, hair cell regeneration is controlled via dynamic interactions between Notch and Wnt/beta-catenin signaling, and likely also between Fgf and the retinoic acid signaling pathways. Less is known about what initiates regeneration and we discuss potential pathways that may trigger proliferation after hair cell damage. PMID- 27266971 TI - The early wound signals. AB - Wounding of tissue barriers, such as epithelia, disrupts homeostasis and allows infection. Within minutes, animals detect injury and respond to it by recruitment of phagocytes and barrier breach closure. The signals that activate these first events are scarcely known. Commonly considered are cytoplasmic factors released into the extracellular space by lysing cells (Damage Associated Molecular Patterns, DAMPs). DAMPs activate inflammatory gene transcription through pattern recognition receptors. But the promptness of wound responses is difficult to explain by transcriptional mechanisms alone. This review highlights the emerging role of nonlytic stress signals in the rapid detection of wounds. PMID- 27266974 TI - Influence of Polarization on Carbohydrate Hydration: A Comparative Study Using Additive and Polarizable Force Fields. AB - Carbohydrates are known to closely modulate their surrounding solvent structures and influence solvation dynamics. Spectroscopic investigations studying far-IR regions (below 1000 cm(-1)) have observed spectral shifts in the libration band (around 600 cm(-1)) of water in the presence of monosaccharides and polysaccharides. In this paper, we use molecular dynamics simulations to gain atomistic insight into carbohydrate-water interactions and to specifically highlight the differences between additive (nonpolarizable) and polarizable simulations. A total of six monosaccharide systems, alpha and beta anomers of glucose, galactose, and mannose, were studied using additive and polarizable Chemistry at HARvard Macromolecular Mechanics (CHARMM) carbohydrate force fields. Solvents were modeled using three additive water models TIP3P, TIP4P, and TIP5P in additive simulations and polarizable water model SWM4 in polarizable simulations. The presence of carbohydrate has a significant effect on the microscopic water structure, with the effects being pronounced for proximal water molecules. Notably, disruption of the tetrahedral arrangement of proximal water molecules was observed due to the formation of strong carbohydrate-water hydrogen bonds in both additive and polarizable simulations. However, the inclusion of polarization resulted in significant water-bridge occupancies, improved ordered water structures (tetrahedral order parameter), and longer carbohydrate-water H bond correlations as compared to those for additive simulations. Additionally, polarizable simulations also allowed the calculation of power spectra from the dipole-dipole autocorrelation function, which corresponds to the IR spectra. From the power spectra, we could identify spectral signatures differentiating the proximal and bulk water structures, which could not be captured from additive simulations. PMID- 27266975 TI - Health-related quality of life after maxillectomy: obturator rehabilitation compared with flap reconstruction. AB - Health-related quality of life (QoL) reported by patients has the potential to improve care after ablative surgery of the midface, as existing treatment algorithms still generally revolve around outcomes assessed traditionally only by clinicians. Decisions in particular relate to reconstruction with a flap compared with rehabilitation with an obturator, the need for adjuvant treatment, and morbidity related to the size of the defect. We prospectively collected health related QoL assessments for 39 consecutive patients treated by maxillectomy between 01 January 2010 and 31 December 2014 using the University of Washington Quality of Life Questionnaire, and who had a mean (SD) duration of follow-up of 14 (4). We made sub-group analyses using paired t tests and analysis of variance (ANOVA) to compare reconstruction with a flap with rehabilitation with obturators, size of the vertical defect, and whether adjuvant treatment with radiotherapy or chemoradiotherapy adversely affected it. Overall there was a significant decrease in health-related QoL after treatment compared with before (p<0.001), but there was no significant difference in the effects of any of the paired reconstructive and rehabilitation treatments on it. Obturators remain an important option for rehabilitation in selected patients in addition to reconstruction with a flap. We found that neither increasing the size of the vertical defect (in an attempt to ensure clear margins) nor the use of postoperative radiotherapy seemed to have any adverse effect on QoL. More patients are required before we can conclude that the potential survival benefits of such measures may outweigh any adverse effects. PMID- 27266976 TI - Cross-cover of oral and maxillofacial surgery out-of-hours: an audit of a new adult treatment clinic. AB - We present our experience of launching the adult treatment clinic - a daytime clinic for semiurgent referrals to oral and maxillofacial surgery (OMFS). This has proved to be an effective way in which cross-covering junior doctors could refer patients for a safe and efficient review in a supervised environment. PMID- 27266977 TI - Outcomes of treatment of fractures of the frontal sinus: review from a tertiary multispecialty craniofacial trauma service. AB - There are no agreed national guidelines for the treatment of fractures of the frontal sinus and the naso-orbitoethmoid complex. The Oxford University Hospitals Craniofacial Trauma unit was set up five years ago as a joint oral and maxillofacial, ENT, and neurosurgical service, and we present our experience to date in the treatment of patients with such fractures. The study includes 91 patients with data collected from a prospective database. Patients underwent cranialisation if they met the criteria of persistent leak of cerebrospinal fluid (CSF), displaced fracture of the posterior wall or obstruction of the nasofrontal outflow tract. The mean follow-up time was 42 months (range 1-10 years). Three groups of patients were analysed. Group 1 met the criteria for, and were treated by, cranialisation (n=50). Group 2 met the criteria for cranialisation, but were treated conservatively because of coexisting conditions (n=8). Group 3 did not match the criteria for treatment, and were managed conservatively (n=33). The numbers of patients with complications or who required further operation were: group 1 (4/50), group 2 (3/8), and group 3 (3/33). There were significantly fewer complications among those patients who met the operative criteria and were treated by cranialisation than among those treated conservatively (p=0.04). These outcomes from one dedicated multispecialist craniofacial trauma unit in the UK may help surgeons who care for patients with this specific group of injuries. Our morbidity was in keeping with published figures. PMID- 27266978 TI - Similar Fecal Microbiota Signatures in Patients With Diarrhea-Predominant Irritable Bowel Syndrome and Patients With Depression. AB - BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) often have psychiatric comorbidities. Alterations in the intestinal microbiota have been associated with IBS and depression, but it is not clear if there is a microbial relationship between these disorders. We studied the profiles of fecal microbiota samples from patients with IBS, depression, or comorbidities of IBS and depression; we determined the relationships among these profiles and clinical and pathophysiological features of these disorders. METHODS: We used 454 pyrosequencing to analyze fecal microbiota samples from 100 subjects (40 with diarrhea-predominant IBS [IBS-D], 15 with depression, 25 with comorbidities of IBS and depression, and 20 healthy individuals [controls]), recruited at Peking University. Abdominal and psychological symptoms were evaluated with validated questionnaires. Visceral sensitivity was evaluated using a barostat. Colonic mucosal inflammation was assayed by immunohistochemical analyses of sigmoid tissue biopsy specimens. RESULTS: Fecal microbiota signatures were similar between patients with IBS-D and depression in that they were less diverse than samples from controls and had similar abundances of alterations. They were characterized by high proportions of Bacteroides (type I), Prevotella (type II), or nondominant microbiota (type III). Most patients with IBS-D or depression had type I or type II profiles (IBS-D had 85% type I and type II profiles, depression had 80% type I and type II profiles). Colon tissues from patients with type I or type II profiles had higher levels of inflammatory markers than colon tissues from patients with type III profiles. The level of colon inflammation correlated with the severity of IBS symptoms. CONCLUSIONS: Patients with IBS-D and depression have similar alterations in fecal microbiota; these might be related to the pathogenesis of these disorders. We identified 3 microbial profiles in patients that could indicate different subtypes of IBS and depression or be used as diagnostic biomarkers. PMID- 27266979 TI - Incidence of Achalasia in South Australia Based on Esophageal Manometry Findings. AB - BACKGROUND & AIMS: Achalasia is a disorder of esophageal motility with a reported incidence of 0.5 to 1.6 per 100,000 persons per year in Europe, Asia, Canada, and America. However, estimates of incidence values have been derived predominantly from retrospective searches of databases of hospital discharge codes and personal communications with gastroenterologists, and are likely to be incorrect. We performed a cohort study based on esophageal manometry findings to determine the incidence of achalasia in South Australia. METHODS: We collected data from the Australian Bureau of Statistics on the South Australian population. Cases of achalasia diagnosed by esophageal manometry were identified from the 3 adult manometry laboratory databases in South Australia. Endoscopy reports and case notes were reviewed for correlations with diagnoses. The annual incidence of achalasia in the South Australian population was calculated for the decade 2004 to 2013. Findings were standardized to those of the European Standard Population based on age. RESULTS: The annual incidence of achalasia in South Australia ranged from 2.3 to 2.8 per 100,000 persons. The mean age at diagnosis was 62.1 +/ 18.1 years. The incidence of achalasia increased with age (Spearman rho, 0.95; P < .01). The age-standardized incidence ranged from 2.1 (95% CI, 1.8-2.3) to 2.5 (95% CI, 2.2-2.7). CONCLUSIONS: Based on a cohort study of esophageal manometry, we determined the incidence of achalasia in South Australia to be 2.3 to 2.8 per 100,000 persons and to increase with age. South Australia's relative geographic isolation and the population's access to manometry allowed for more accurate identification of cases than hospital code analyses, with a low probability of missed cases. PMID- 27266980 TI - Low Serum Vitamin D During Remission Increases Risk of Clinical Relapse in Patients With Ulcerative Colitis. AB - BACKGROUND & AIMS: Vitamin D levels have been associated with disease activity in patients with ulcerative colitis (UC), but it is unclear whether they affect the risk of disease relapse. We sought to determine the association between baseline vitamin D levels during a period of clinical remission and risk of subsequent UC relapse. METHODS: We performed a physician-blinded prospective study of 70 patients with UC in clinical remission followed up after a surveillance colonoscopy at a tertiary academic medical center. Serum samples were collected at the time of colonoscopy and baseline endoscopic and histologic activity were determined. Levels of 25-hydroxy-vitamin D were measured using an enzyme-linked immunosorbent assay. The primary outcome was rate of clinical relapse, determined over 12 months. RESULTS: The mean baseline vitamin D level was lower among patients with relapse (29.5 ng/mL) than without (50.3 ng/mL) (P = .001). Remission vitamin D level (<=35 ng/mL) was associated with a risk of clinical relapse (odds ratio, 1.25; 95% confidence interval [CI], 1.01-1.56; P = .044) over 12 months, independent of endoscopic or histologic grade at enrollment. A receiver operating characteristic curve of vitamin D levels for the outcome of relapse had an area under the curve of 0.72; and a serum level of 35 ng/mL or less had a sensitivity of 70% (95% CI, 46%-88%) and a specificity of 74% (95% CI 57%-83%) for predicting risk of clinical relapse. CONCLUSIONS: Serum levels of vitamin D of 35 ng/mL or less during periods of clinical remission increase the risk of UC relapse. Clinical trials to obtain vitamin D levels higher than this threshold should be considered. PMID- 27266981 TI - Regarding "Colorectal Cancer Screening Quality Measures: Beyond Colonoscopy". PMID- 27266983 TI - Endometrial tuberculosis compounding polycystic ovary syndrome in a subfertile woman: a case report. AB - BACKGROUND: Asymptomatic female genital tuberculosis can impair tubal and endometrial function and later present as subfertility. A majority of the patients with genital tuberculosis in endemic regions present with subfertility and the delay in presentation, coupled with the potential the disease has in mimicking other gynecological conditions, renders it elusive. In addition to the challenge of diagnosing genital tuberculosis, fertility outcomes after treatment are not impressive. This is particularly so in the background of another confounding subfertility factor to which interventional efforts may initially be directed, at the expense of undiagnosed genital tuberculosis. We therefore present a case of subfertility due to endometrial tuberculosis, but confounded by other subfertility factors notably polycystic ovary syndrome. To the best of our knowledge this case report is the first of its kind in the literature. CASE PRESENTATION: This is a case report of a 42-year-old woman of African descent who presented to our fertility clinic with a 10-year history of primary subfertility and amenorrhea of 6 years duration. She was a nurse in a medical ward and had no prior history of tuberculosis. She had undergone a diagnostic laparoscopy 8 years prior which demonstrated dense pelvic adhesions and an impression of tubal factor subfertility was made. At presentation, her gonadal hormone profile and pelvic ultrasound were consistent with polycystic ovary syndrome. A negative response to a progesterone challenge test prompted a hysteroscopic evaluation which revealed endometrial atrophy. Endometrial biopsies confirmed histological features consistent with tuberculosis. Normal endometrial function was not restored despite adequate treatment and her options were limited to surrogacy or adoption. CONCLUSIONS: Genital tuberculosis is elusive in presentation and clinicians should consider it in patients with amenorrhea and/or tubal disease from tuberculosis-endemic regions. Due to the attendant high cost of fertility treatment and associated poor fertility outcomes, it is prudent to explore options to diagnose it early. A routine endometrial biopsy in a patient with subfertility in a tuberculosis-endemic area would be pragmatic. An alternative algorithm in management would be risk stratification prior to endometrial biopsy. PMID- 27266982 TI - Global Trends in Pancreatic Cancer Mortality From 1980 Through 2013 and Predictions for 2017. AB - BACKGROUND & AIMS: Pancreatic cancer is a leading cause of cancer mortality, and its mortality has not decreased in recent years. We sought to determine global trends in pancreatic cancer mortality. METHODS: We derived data on deaths from pancreatic cancer from the World Health Organization database for 59 countries from 1980 through 2013. Age-standardized mortalities were computed for persons of all ages and for persons 35-64 years old; for selected countries, they were computed for persons 25-49 years old. Joinpoint regression models were used to identify significant changes in mortality. For selected larger countries, we predicted number of deaths and mortality for 2017. RESULTS: Between 1980 and 2013, overall pancreatic cancer mortality in men increased in the European Union (EU) as well as in Southern and Eastern Europe, Brazil, Japan, and Republic of Korea. Overall pancreatic cancer mortality decreased in most Northern European countries, Australia, Canada, Mexico, and the United States (US). In women, mortality increased in the EU, Brazil, US, Japan, and Republic of Korea but decreased in Canada and Mexico. In 2012, Eastern Europe and Japan had the highest pancreatic cancer mortality for both sexes. In men 25-49 years old, mortality decreased in the EU, US, Japan, and most large European countries. On the basis of our data, we predict overall pancreatic cancer mortality in 2017 to level off in men in the EU and US but increase in Japan. In women, mortality will continue to increase in most countries except the US; the greatest increase is predicted to occur in Japan. CONCLUSIONS: Mortality from pancreatic cancer has not decreased as it has for other cancers in recent years. A notable exception is a decrease in mortality in men 25-49 years old, which could indicate a reversal in the current increasing global trends. PMID- 27266984 TI - T follicular helper cells in patients with acute schistosomiasis. AB - BACKGROUND: The role of T follicular helper (Tfh) cells in schistosome infection is not fully defined. In a previous study, a higher frequency of circulating PD 1(+)CXCR5(+)CD4(+) Tfh cells was observed in patients with chronic schistosomiasis relative to healthy controls (HCs) and it correlated positively with the level of soluble egg antigen (SEA) specific antibodies in serum. However, the function of Tfh cells in patients with acute schistosomiasis remains elusive; this was investigated in the present study. METHODS: The frequency of circulating Tfh cells and the expression of inducible T cell co-stimulator (ICOS), programmed cell death 1 (PD-1) and B cell subsets were analyzed in 12 patients with acute schistosomiasis and 10 HCs by flow cytometry. The expression of Bcl6, c-Maf and IL-21 mRNA were detected by quantitative real-time reverse transcriptase PCR (qRT-PCR). The concentration of serum IL-21 and IgG specific to Schistosoma japonicum antigen were then determined by enzyme linked immunosorbent assay (ELISA). Correlations between PD-1(+)CXCR5(+)CD4(+) Tfh cells, memory B cells and IgG specific to S. japonicum were analyzed by Spearman's rank correlation. RESULTS: The frequency of PD-1(+)CXCR5(+)CD4(+) Tfh and memory B cells was increased in acute schistosomiasis patients relative to HCs. Moreover, the levels of IL-21 in serum and the expression of IL-21 mRNA were higher in acute schistosomiasis patients. However, there was no significant correlation between PD-1(+)CXCR5(+)CD4(+) Tfh cells, memory B cells and IgG specific to S. japonicum antigen in patients with acute schistosomiasis. CONCLUSIONS: PD 1(+)CXCR5(+)CD4(+) Tfh cells in peripheral blood are involved in the immune response of patients with acute schistosomiasis. Understanding the immunological mechanism is helpful for the development of vaccination strategies to control schistosomiasis. PMID- 27266986 TI - Impact of lifestyle interventions on depressive symptoms in individuals at-risk of, or with, type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND AND AIM: Depression affects one in four individuals with type 2 diabetes mellitus (T2DM). The impact of T2DM lifestyle interventions on depression is unclear. The aim of this analysis was to examine the influence of lifestyle interventions on depressive symptoms scores in individuals at-risk of or with T2DM. METHOD AND RESULTS: Major bibliographic databases were searched for studies published in English from 1990 to 2015. Meta-analysis was conducted by random-effects model. Nineteen studies were included in the meta-analyses. A significant reduction in depression scores was shown for lifestyle interventions in the pooled analysis (Standardized Mean Difference (SMD): -0.165; 95%CI: 0.265, -0.064; I(2):67.9%) and when limited to individuals with T2DM (SMD: 0.202; 95%CI: -0.288, -0.079; I(2):72.5%). In subgroup analyses the most effective intervention methods were face-to-face individual consultations (SMD: 0.241; 95%CI: -0.403, -0.078, I(2): 50.8%) with a duration of <=6 months (SMD: 0.203; 95%CI: -0.381, -0.026, I(2):59.9%). Interventions were most effective when delivered four times a month (SMD: -0.247; 95%CI: -0.441, -0.053, I(2):76.3%). CONCLUSIONS: Lifestyle interventions were effective in improving depression among people with T2DM. PMID- 27266985 TI - Rationale and design of the Chinese Atrial Fibrillation Registry Study. AB - BACKGROUND: Robust data on the contemporary management of atrial fibrillation (AF) patients in China are limited. Importantly current practice in AF management has changing dramatically in recent years. Data from a large registry study will enable us to evaluate the uptake and outcomes with different therapies in a large Chinese AF population. METHODS/DESIGN: The Chinese Atrial Fibrillation Registry study (CAFR) aims to enroll 20,000 consecutive atrial fibrillation (AF) patients from 32 tertiary and non-tertiary hospitals in Beijing, China, and follow up these patients every 6 months until 2020. Key data collected includes basic sociodemographic information, symptoms and signs, medical history, results of physical examination and laboratory test, details of treatments and personal insurance status. For patients who consent, 5 ml of blood sample will be stored at -80 degrees C for future analyses of biomarkers. At each 6 month follow up visit, data relating to clinical outcomes will be collected. Data from a randomly selected 10 % of patients will be internally validated with their raw source data. Ischemic stroke events will be adjudicated by an independent endpoint committee. DISCUSSION: CAFR will be one of the largest registries of Asian AF patients (and the largest in Chinese AF patients), as well as providing the longest follow up. This study would provide a valuable opportunity for 'real world' clinical epidemiology with insights into the uptake (and outcomes) of contemporary AF management. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OCH-13003729 . Registered 22 October 2013. PMID- 27266987 TI - Response to letter to the editor: Gallo F et al., "The economic burden of severe hypoglycemia: Two sides of the same coin" Nutr Metab Cardiovasc Dis. 2016;26:850 851. PMID- 27266988 TI - Concordance of dietary sodium intake and concomitant phosphate load: Implications for sodium interventions. AB - BACKGROUND AND AIMS: Both a high dietary sodium and high phosphate load are associated with an increased cardiovascular risk in patients with chronic kidney disease (CKD), and possibly also in non-CKD populations. Sodium and phosphate are abundantly present in processed food. We hypothesized that (modulation of) dietary sodium is accompanied by changes in phosphate load across populations with normal and impaired renal function. METHODS AND RESULTS: We first investigated the association between sodium and phosphate load in 24-h urine samples from healthy controls (n = 252), patients with type 2 diabetes mellitus (DM, n = 255) and renal transplant recipients (RTR, n = 705). Secondly, we assessed the effect of sodium restriction on phosphate excretion in a nondiabetic CKD cohort (ND-CKD: n = 43) and a diabetic CKD cohort (D-CKD: n = 39). Sodium excretion correlated with phosphate excretion in healthy controls (R = 0.386, P < 0.001), DM (R = 0.490, P < 0.001), and RTR (R = 0.519, P < 0.001). This correlation was also present during regular sodium intake in the intervention studies (ND-CKD: R = 0.491, P < 0.001; D-CKD: R = 0.729, P < 0.001). In multivariable regression analysis, sodium excretion remained significantly correlated with phosphate excretion after adjustment for age, gender, BMI, and eGFR in all observational cohorts. In ND-CKD and D-CKD moderate sodium restriction reduced phosphate excretion (31 +/- 10 to 28 +/- 10 mmol/d; P = 0.04 and 26 +/- 11 to 23 +/- 9 mmol/d; P = 0.02 respectively). CONCLUSIONS: Dietary exposure to sodium and phosphate are correlated across the spectrum of renal function impairment. The concomitant reduction in phosphate intake accompanying sodium restriction underlines the off-target effects on other nutritional components, which may contribute to the beneficial cardiovascular effects of sodium restriction. (f) Registration numbers: Dutch Trial Register NTR675, NTR2366. PMID- 27266989 TI - Biological effects of marine diesel oil exposure in red king crab (Paralithodes camtschaticus) assessed through a water and foodborne exposure experiment. AB - Shipping activities are expected to increase in the Arctic Seas. Today, the majority of vessels are using marine diesel oil (MDO) as propulsion fuel. However, there is a general lack of knowledge of how cold-water marine species respond to acute exposures to MDO. Arctic red king crabs (Paralithodes camtschaticus) were exposed to mechanically dispersed MDO in a flow-through exposure system for one week followed by three weeks of recovery. Observations of increased movements in exposed crabs were interpreted as avoidance behaviour. Further, glutathione peroxidase activity increased in high exposed crab, the catalase activity showed an insignificant increase with exposure, while no differences between groups were observed for lipid peroxidation and acetylcholinesterase activity. After three weeks of recovery in clean seawater, polycyclic aromatic hydrocarbons concentrations in the crabs were significantly reduced, with no specific biomarker responses in exposed groups compared to the control. The results suggest that effects from instantaneous MDO spill only will have short-term effects on the red king crab. PMID- 27266990 TI - Systemic and Brain Pharmacokinetics of Perforin Inhibitor Prodrugs. AB - We have recently reported that by converting a perforin inhibitor into an l-type amino acid transporter 1 (LAT1)-utilizing prodrug its cellular uptake can be greatly increased. The aim of the present study was to determine the in vivo and brain pharmacokinetics of two perforin inhibitors and their LAT1-utilizing prodrugs 1 and 2. In addition, the brain uptake mechanism and entry into primary mouse cortical neurons and astrocytes were evaluated. After 23 MUmol/kg i.p. bolus injection, the prodrugs' unbound area under the concentration curve in brain was 0.3 nmol/g * min, whereas the parent drugs could not reach the brain. The unbound brain concentrations of the prodrugs after 100 MUM in situ mouse brain perfusion were 521.4 +/- 46.9 and 126.9 +/- 19.9 pmol/g for prodrugs 1 and 2, respectively. The combination of competing transporter substrates for LAT1, l tryptophan, and for organic anion transporting polypeptides, probenecid, decreased the brain concentrations to 352.4 +/- 44.5 and 70.9 +/- 7.0 pmol/g, respectively. In addition, in vitro uptake studies showed that at 100 MUM prodrug 1 had 3.4-fold and 4.5-fold higher uptake rate into neurons and astrocytes, respectively, compared to its parent drug. Thus, the prodrugs enhance significantly the therapeutic potential of the parent drugs for the treatment of disorders of central nervous system in which neuroinflammation is involved. PMID- 27266991 TI - Anatomical Effects of Axillary Nodes Dissection on Rat Lymphatic System Model: Indocyanine Green Mapping and Dissection. AB - BACKGROUND: Axillary nodes dissection (AND) is an important risk factor for the appearance of breast cancer-related lymphedema (BCRL). The anatomy and pathophysiology leading to the development of BCRL after AND are not completely understood. Despite the existence of lymphedema models after AND, none of them were able to create lymphedemas without additional chemical inflammatory drugs or auxiliary physical techniques (radiotherapy). In this study, we aimed to describe the anatomical changes of AND on a rat's front leg before and after a new surgery technique. METHODS AND RESULTS: AND was performed on seven Wistar rats with a new, posterior surgical approach. Indocyanine green mapping was done before and after surgery to detect "normal and secondary superficial lymphatic pathways" of the operated rat's front legs. Twelve months after surgery, dissections were performed. Subcutaneous blue dye injection of the hand was used to observe superficial and deep lymphatic pathways. Postsurgery, an acute edema of arm and shoulder appeared and persisted for 14-21 days. However, none of the rats showed a chronic secondary lymphedema. In two cases, seromas also appeared. All rats showed substitution functional lymphatic pathways as perforating lymph vessels around the surgical sites. CONCLUSION: This is the first description of perforating lymph vessels as lymphatic substitution pathways after AND on rats. These results help to understand why a chronic secondary lymphedema could not be created in rats after AND without additional chemical or physical interventions. PMID- 27266993 TI - Pressure Controlled Chemical Gardens. AB - The dissolution of metal salts in silicate solution can result in the growth of hollow precipitate tubes. These "chemical gardens" are a model of self organization far from the equilibrium and create permanent macroscopic structures. The reproducibility of the growth process is greatly improved if the solid salt seed is replaced by a salt solution that is steadily injected by a pump; however, this modification of the original experiment eliminates the membrane-based osmotic pump at the base of conventional chemical gardens and does not allow for analyses in terms of the involved pressure. Here we describe a new experimental method that delivers the salt solution according to a controlled hydrostatic pressure. In one form of the experiment, this pressure slowly decreases as zinc sulfate solution flows into the silicate-containing reaction vessel, whereas a second version holds the respective solution heights constant. In addition to three known growth regimes (jetting, popping, budding), we observe single tubes that fill the vessel in a horizontally undulating but vertically layered fashion (crowding). The resulting, dried product has a cylindrical shape, very low density, and one continuous connection from top to bottom. We also present phase diagrams of these growth modes and show that the flow characteristics of our experiments follow a reaction-independent Hagen-Poiseuille equation. PMID- 27266994 TI - A new regulatory mechanism controlling carotenogenesis in the fungus Mucor circinelloides as a target to generate beta-carotene over-producing strains by genetic engineering. AB - BACKGROUND: Carotenoids are natural pigments with antioxidant properties that have important functions in human physiology and must be supplied through the diet. They also have important industrial applications as food colourants, animal feed additives and nutraceuticals. Some of them, such as beta-carotene, are produced on an industrial scale with the use of microorganisms, including fungi. The mucoral Blakeslea trispora is used by the industry to produce beta-carotene, although optimisation of production by molecular genetic engineering is unfeasible. However, the phylogenetically closely related Mucor circinelloides, which is also able to accumulate beta-carotene, possesses a vast collection of genetic tools with which to manipulate its genome. RESULTS: This work combines classical forward and modern reverse genetic techniques to deepen the regulation of carotenoid synthesis and generate candidate strains for biotechnological production of beta-carotene. Mutagenesis followed by screening for mutants with altered colour in the dark and/or in light led to the isolation of 26 mutants that, together with eight previously isolated mutants, have been analysed in this work. Although most of the mutants harboured mutations in known structural and regulatory carotenogenic genes, eight of them lacked mutations in those genes. Whole-genome sequencing of six of these strains revealed the presence of many mutations throughout their genomes, which makes identification of the mutation that produced the phenotype difficult. However, deletion of the crgA gene, a well known repressor of carotenoid biosynthesis in M. circinelloides, in two mutants (MU206 and MU218) with high levels of beta-carotene resulted in a further increase in beta-carotene content to differing extents with respect to the crgA single-null strain; in particular, one strain derived from MU218 was able to accumulate up to 4 mg/g of beta-carotene. The additive effect of crgA deletion and the mutations present in MU218 suggests the existence of a previously unknown regulatory mechanism that represses carotenoid biosynthesis independently and in parallel to crgA. CONCLUSIONS: The use of a mucoral model such as M. circinelloides can allow the identification of the regulatory mechanisms that control carotenoid biosynthesis, which can then be manipulated to generate tailored strains of biotechnological interest. Mutants in the repressor crgA and in the newly identified regulatory mechanism generated in this work accumulate high levels of beta-carotene and are candidates for further improvements in biotechnological beta-carotene production. PMID- 27266992 TI - Experimental psychopathology paradigms for alcohol use disorders: Applications for translational research. AB - In spite of high prevalence and disease burden, scientific consensus on the etiology and treatment of Alcohol Use Disorder (AUD) has yet to be reached. The development and utilization of experimental psychopathology paradigms in the human laboratory represents a cornerstone of AUD research. In this review, we describe and critically evaluate the major experimental psychopathology paradigms developed for AUD, with an emphasis on their implications, strengths, weaknesses, and methodological considerations. Specifically we review alcohol administration, self-administration, cue-reactivity, and stress-reactivity paradigms. We also provide an introduction to the application of experimental psychopathology methods to translational research including genetics, neuroimaging, pharmacological and behavioral treatment development, and translational science. Through refining and manipulating key phenotypes of interest, these experimental paradigms have the potential to elucidate AUD etiological factors, improve the efficiency of treatment developments, and refine treatment targets thus advancing precision medicine. PMID- 27266995 TI - Accuracy Assessment of Immediate and Delayed Implant Placements Using CAD/CAM Surgical Guides. AB - The aim of this study is to assess the accuracy of immediately placed implants using Anatomage Invivo5 computer-assisted design/computer-assisted manufacturing (CAD/CAM) surgical guides and compare the accuracy to delayed implant placement protocol. Patients who had implants placed using Anatomage Invivo5 CAD/CAM surgical guides during the period of 2012-2015 were evaluated retrospectively. Patients who received immediate implant placements and/or delayed implant placements replacing 1-2 teeth were included in this study. Pre- and postsurgical images were superimposed to evaluate deviations at the crest, apex, and angle. A total of 40 implants placed in 29 patients were included in this study. The overall mean deviations measured at the crest, apex, and angle were 0.86 mm, 1.25 mm, and 3.79 degrees , respectively. The means for the immediate group deviations were: crest = 0.85 mm, apex = 1.10, and angle = 3.49 degrees . The means for the delayed group deviations were: crest = 0.88 mm, apex = 1.59, and angle = 4.29 degrees . No statistically significant difference was found at the crest and angle; however, there was a statistically significant difference between the immediate and delayed group at the apex, with the immediate group presenting more accurate placements at the apical point than the delayed group. CAD/CAM surgical guides can be reliable tools to accurately place implants immediately and/or in a delayed fashion. No statistically significant differences were found between the delayed and the immediate group at the crest and angle, however apical position was more accurate in the immediate group. PMID- 27266996 TI - Experimental Proof for the Role of Nonlinear Photoionization in Plasmonic Phototherapy. AB - Targeting individual cells within a heterogeneous tissue is a key challenge in cancer therapy, encouraging new approaches for cancer treatment that complement the shortcomings of conventional therapies. The highly localized interactions triggered by focused laser beams promise great potential for targeting single cells or small cell clusters; however, most laser-tissue interactions often involve macroscopic processes that may harm healthy nearby tissue and reduce specificity. Specific targeting of living cells using femtosecond pulses and nanoparticles has been demonstrated promising for various potential therapeutic applications including drug delivery via optoporation, drug release, and selective cell death. Here, using an intense resonant femtosecond pulse and cell specific gold nanorods, we show that at certain irradiation parameters cell death is triggered by nonlinear plasmonic photoionization and not by thermally driven processes. The experimental results are supported by a physical model for the pulse-particle-medium interactions. A good correlation is found between the calculated total number and energy of the generated free electrons and the observed cell death, suggesting that femtosecond photoionization plays the dominant role in cell death. PMID- 27266997 TI - Design and synthesis of N-(5-chloro-2,4-dihydroxybenzoyl)-(R)-1,2,3,4 tetrahydroisoquinoline-3-carboxamides as novel Hsp90 inhibitors. AB - Heat shock protein 90 (Hsp90) is an attractive chemotherapeutic target for antitumor drug development. Herein, we reported the design and synthesis of two series of novel N-(5-chloro-2,4-dihydroxybenzoyl)-1,2,3,4-tetrahydroisoquinoline 3- carboxamides as Hsp90 inhibitors using (S)-Tic (1,2,3,4-tetrahydroisoquinoline 3- carboxylic acid) (A1-13) and (R)-Tic (B1-13) as scaffold, respectively. Cellular thermal shift assay (CETSA) screening showed that compounds B1-13 with (R)-Tic scaffold exhibited potent ability to stabilize Hsp90alpha. Compound B7 showed not only the most potent ability to induce thermal stabilization of Hsp90alpha but also the strongest cytotoxicity. The IC50 values of B7 were 0.98 MUM and 1.74 MUM against the proliferation of human breast cancer MDA-MB-231 and human cervical cancer HeLa cell lines, respectively. Moreover, CETSA melt and ITDRFCETSA (isothermal dose-response fingerprint) curves confirmed that B7 bound to Hsp90alpha in 293T cells. Western blotting results indicated that B7 induced the degradation of Hsp90 clients CDK4, Her2, Cdc-2 and C-raf. In addition, docking and Molecular dynamics (MD) refinement of the B7-Hsp90 complex showed that the binding model of B7 to Hsp90 was similar with that of 8-benzyladenines. The overall properties warrant compound B7 a promising lead for the development of Hsp90 inhibitor antitumor drugs. PMID- 27266998 TI - Design, synthesis, and pharmacological evaluation of multitarget-directed ligands with both serotonergic subtype 4 receptor (5-HT4R) partial agonist and 5-HT6R antagonist activities, as potential treatment of Alzheimer's disease. AB - 5-HT4 receptor (5-HT4R) activation and blockade of the 5-HT6 receptor (5-HT6R) are known to enhance the release of numerous neurotransmitters whose depletion is implicated in Alzheimer's disease (AD). Furthermore, 5-HT4R agonists seem to favor production of the neurotrophic soluble amyloid protein precursor alpha (sAPPalpha). Consequently, combining 5-HT4R agonist/5-HT6R antagonist activities in a single chemical compound would constitute a novel approach able to display both a symptomatic and disease-modifying effect in AD. Seventeen novel derivatives of RS67333 (1) were synthesized and evaluated as potential dual target compounds. Among them, four agents showed nanomolar and submicromolar affinities toward 5-HT4R and 5-HT6R, respectively; one of them, 7m, was selected on the basis of its in vitro affinity (Ki5-HT4R = 5.3 nM, Ki5-HT6R = 219 nM) for further in vivo experiments, where 7m showed an antiamnesic effect in the mouse at 1 mg/kg ip. PMID- 27266999 TI - Development of 4,5-dihydro-benzodiazepinone derivatives as a new chemical series of BRD4 inhibitors. AB - Bromodomains (BRDs) are protein interaction modules that selectively recognize epsilon -N-lysine residues, serving as key epigenetic readers and play a key role in epigenetic regulation of gene transcription. Bromodomain-containing protein 4 (BRD4), a protein containing two BRDs termed BD1 and BD2, has emerged as an attractive candidate for the development of inhibitors targeting gene transcription in several types of cancers. In this study, we made structural modifications of previously reported BRD4 inhibitors, to develop new chemical scaffold 3,4-dihydroquinoxalin-2(1H)-one. Four series of compounds (compounds 7 10) were synthesized, and the BRD4-inhibitory activity and anti-proliferative effect of these compounds were evaluated. We found compound 10d has remarkable anti-proliferative activities toward leukemia cells and could induce apoptosis by mitochondrial pathways. Notably, the analysis of molecular docking suggested that hydrophobic interaction was essential for compound 10d to bind to BD1. In conclusion, these results demonstrate the potential of compound 10d to be utilized as a BRD4 inhibitor with apoptosis inducing effect in future leukemia therapy. PMID- 27267000 TI - Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues. AB - Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation. PMID- 27267001 TI - A series of pyrido[2,3-b]pyrazin-3(4H)-one derivatives as aldose reductase inhibitors with antioxidant activity. AB - A series of pyrido[2,3-b]pyrazin-3(4H)-one based derivatives were designed as inhibitors of aldose reductase (ALR2), the enzyme which plays a key role in the development of diabetes complications as well as in the oxidative stress processes associated with diabetes and other pathologies. Most of the derivatives, having a substituted C2 aromatic group and a N4 acetic acid group on the core structure, were found to be potent and selective aldose reductase inhibitors with submicromolar IC50 values, and 9c was the most active with IC50 value 0.009 MUM. Particularly, a number of the designed compounds bearing phenolic hydroxyl substituted C2-styryl side chain showed excellent not only in ALR2 inhibition but also in antioxidant, and among these 11i was proved to be the top one with an antioxidant ability even comparable to that of the well-known antioxidant Trolox. Structure-activity relationship and molecular docking studies highlighted the importance of phenolic hydroxyl substituents and vinyl spacer in C2 side chain of the scaffold for the construction of efficient and multifunctional ALR2 inhibitors. PMID- 27267002 TI - Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2 yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity. AB - A total of thirty five new N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamide derivatives were synthesized and structures of all the compounds were confirmed on the basis of elemental analysis and collective use of IR, (1)H NMR, (13)C NMR and mass spectral data. Compounds were tested for their ability to inhibit human monoacylglycerol lipase (hMAGL) enzyme. Eight compounds 4, 19-21, 24-26, and 34 reduced the hMAGL activity less than 50% at 100 nM concentrations. The halogen substituted aniline derivatives 20, 21 and 24-26 were found to be most active among all the synthesized compounds having IC50 value in the range of 6.5-9 nM. Twenty five compounds were selected by NCI, USA for one dose anticancer screening. Compound 21 (NSC: 780167) and 24 (NSC: 780168) fulfilled prearranged doorstep growth inhibition criteria and further selected for NCI full panel five dose assay at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 MUM). Both the compounds 21 and 24 were found to be most active against MCF7 and MDA-MB-468 breast cancer cell lines. The GI50 value of 32.5 nM (MCF7) and 23.8 nM (MDA-MB-468) was observed for compound 21. Compound 24 showed GI50 values of 37.1 nM against MCF7 breast cancer cell line and 25.1 nM against MDA-MB-468 breast cancer cell line. PMID- 27267003 TI - Do cinnamylideneacetophenones have antioxidant properties and a protective effect toward the oxidation of phosphatidylcholines? AB - Cinnamylideneacetophenones (CA) are an important group of alpha,beta,gamma,delta diunsaturated ketones that have been widely used in a variety of synthetic transformations. Biological studies concerning these compounds are scarce and refer mainly to antiviral and antibacterial evaluations. Curcumin (CR), a natural polyphenol, is a yellow pigment extracted from the plant Curcuma longa, which is one of the major spices used in the Indian culinary. It has been reported that CR has cancer chemopreventive properties in a range of animal models of chemical carcinogenesis, along with antioxidative and anti-inflammatory properties. Inspired by the biological activity shown by CR and their structural resemblance with CA, it was considered to study the ability of the latter molecules to inhibit lipid oxidation induced by the hydroxyl radical (Fenton reaction) by electrospray ionization (ESI) mass spectrometry (MS) using phosphatidylcholine (PC) liposomes as a model of cell membrane. Compound 4, holding a methylated hydroxy group in the position R(2), and CR showed similar effects in inhibiting lipid peroxidation. In the presence of 7, the extension of oxidation was higher than the one verified in all other compounds. Other methodologies, namely DPPH radical scavenging and oxygen radical absorption capacity (ORAC) assays, were performed to complement and clarify the results attained by oxidation of PC monitored by ESI-MS and to evaluate the antioxidant profile of compounds. For both assays, compound 7 showed to be rather efficient due to its specific structure. This derivative can form a quite stable allylic radical by abstraction of a hydrogen atom which accounts for these results. PMID- 27267004 TI - 4-Phenylureido/thioureido-substituted 2,2-dimethylchroman analogs of cromakalim bearing a bulky 'carbamate' moiety at the 6-position as potent inhibitors of glucose-sensitive insulin secretion. AB - The synthesis of 2,2-dimethylchromans bearing a 3/4-chloro/cyano-substituted phenylureido or phenylthioureido moiety at the 4-position and an alkoxycarbonylamino ('carbamate') group at the 6-position is described. These new analogs of the potassium channel opener (+/-)-cromakalim were further tested on rat pancreatic islets as putative inhibitors of insulin release and on rat aorta rings as putative vasorelaxants. All compounds inhibited insulin secretion and induced a myorelaxant activity. Compound 14o [R/S-N-3-cyanophenyl-N'-(6-tert butoxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)urea; BPDZ 711] emerged as the most potent inhibitor of the glucose-sensitive insulin releasing process (IC50 = 0.24 MUM) and displayed selectivity towards the pancreatic endocrine tissue. Radioisotopic, fluorimetric and pharmacological investigations were performed on rat pancreatic islet and rat vascular smooth muscle cells in order to decipher its mechanism of action. Our findings suggest that the mechanism of action of 14o is rather unspecific. The compound behaves as a KATP channel opener, a Ca(2+) entry blocker, and promotes an intracellular calcium translocation. PMID- 27267005 TI - Structural optimization of pyridine-type DAPY derivatives to exploit the tolerant regions of the NNRTI binding pocket. AB - Based on the crystallographic studies of diarylpyrimidines (DAPYs), we embarked on incorporating the hydrophilic piperidyl or morpholinyl group into the known DAPY derivatives bearing the pyridine moiety as a core structure, with the double aim to exploit additional interactions with the HIV-1 NNRTI binding pocket (NNIBP), as well as to improve the compound solubility. The antiviral evaluation result show that the most potent compounds I-8b2, I-8b3, I-8b4 and I-8c3 exhibited anti-HIV-1 (IIIB) strain activity ranging from 7.4 nM to 9.4 nM (SI = 168-1283), superior to FDA-approved drugs of nevirapine (NVP), lamivudine (3TC) and delavirdine (DLV), and comparable to etravirine (ETV), zidovudine (AZT) and efavirenz (EFV). Additionally, compounds I-8c2 and I-8c3 showed moderate activity against NNRTI resistant strains baring mutations K103N and Y181C with EC50 values of 6.2 MUM and 6.8 MUM, respectively. Preliminary structure-activity relationships (SARs), reverse transcriptase inhibition efficacy and molecular modeling of selected compounds are also presented. These outcomes support our design hypothesis and demonstrate that the piperidyl group modified pyridine typed DAPY derivatives are highly potent NNRTIs with improved water solubility. PMID- 27267006 TI - Nitrobenzofurazan derivatives of N'-hydroxyamidines as potent inhibitors of indoleamine-2,3-dioxygenase 1. AB - Tryptophan metabolism through the kynurenine pathway is considered as a crucial mechanism in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in tryptophan catabolism in the immune system and it is also considered as an important therapeutic target for the treatment of cancer and other diseases that are linked with kynurenine pathway. In this study, a series of nitrobenzofurazan derivatives of N'-hydroxybenzimidamides (1) and N'-hydroxy-2 phenylacetimidamides (2) were synthesized and their inhibitory activities against human IDO1 enzyme were tested using in-vitro and cellular enzyme activity assay. The optimization leads to the identification of potent compounds, 1d, 2i and 2k (IC50 = 39-80 nM), which are either competitive or uncompetitive inhibitors of IDO1 enzyme. These compounds also showed IDO1 inhibition potencies in the nanomolar range (IC50 = 50-71 nM) in MDA-MB-231 cells with no/negligible amount of cytotoxicity. The stronger selectivity of the potent compounds for IDO1 enzyme over tryptophan 2,3-dioxygenase (TDO) enzyme (312-1593-fold) also makes them very attractive for further immunotherapeutic applications. PMID- 27267007 TI - New cinnamic - N-benzylpiperidine and cinnamic - N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties. AB - Here we describe new families of multi-target directed ligands obtained by linking antioxidant cinnamic-related structures with N-benzylpiperidine (NBP) or N,N-dibenzyl(N-methyl)amine (DBMA) fragments. Resulting hybrids, in addition to their antioxidant and neuroprotective properties against mitochondrial oxidative stress, are active at relevant molecular targets in Alzheimer's disease, such as cholinesterases (hAChE and hBuChE) and monoamine oxidases (hMAO-A and hMAO-B). Hybrids derived from umbellic - NBP (8), caffeic - NBP (9), and ferulic - DBMA (12) displayed balanced biological profiles, with IC50s in the low-micromolar and submicromolar range for hChEs and hMAOs, and an antioxidant potency comparable to vitamin E. Moreover, the caffeic - NBP hybrid 9 is able to improve the differentiation of adult SGZ-derived neural stem cells into a neuronal phenotype in vitro. PMID- 27267008 TI - Preoperative Assessment of Risk Factors. AB - Hemostasis is essential during endoscopic sinus and skull base surgery. Patients must be adequately assessed for bleeding risk to appropriately consent to surgery. The patient and the surgeon must be aware of the individual bleeding risk for a given procedure. A thorough history and physical examination is the best screening methodology available to determine whether a patient requires further hematologic work-up. Included in this assessment should be any medications and herbals that the patient consumes. This ensures a safe evaluation of the patient, streamlines appropriate consultation and testing when necessary, and confers accurate surgical risk assessment. PMID- 27267009 TI - Anesthetic Techniques in Endoscopic Sinus and Skull Base Surgery. AB - Endoscopic sinus approach has become one of the most common surgical techniques for endoscopic sinus and skull base surgery. Anesthetic management has an important impact on the overall patient management, from the preoperative assessment and management to the quality of the surgical field and the postoperative recovery. Hemostasis is critical for adequate anatomical endoscopic visualization. Mild controlled hypotension seems to improve the visibility of the surgical field. Reduction of intraoperative bleeding should be considered during the treatment planning. Preoperative preparations include the optimization of comorbidities and cessation of drugs that may inhibit coagulation. PMID- 27267011 TI - Quality Control Approach to Anticoagulants and Transfusion. AB - Quality can be defined by processes of care and by the characteristics of the care and its outcomes. In terms of blood loss and transfusion, otolaryngologists should be aware of available guidelines, standards for use of blood products, devices and hemostatic agents, outcomes metrics relevant to patients, and tools for implementing quality improvements. This article reviews the definition of health care quality, and discusses the data regarding anticoagulant medications (particularly new oral anticoagulants) and guidelines for blood product transfusion. A brief outline of quality tools is provided to help otolaryngologists create quality plans for themselves and their institutions/systems. PMID- 27267010 TI - Blood-Sparing Techniques in Head and Neck Surgery. AB - Given the risks and potential complications of allogenic blood transfusion (ABT), as well as the expanding population of patients for whom ABT may not be an option, it is important for the treating physician, anesthesiologist, and surgeon to be well-versed in various alternatives. A good grasp of the concepts discussed in this article will help to customize a treatment plan that is specific to each patient's underlying disease and personal preferences without compromising appropriate medical care. PMID- 27267012 TI - Surgical Adhesives in Facial Plastic Surgery. AB - In facial plastic surgery, attaining hemostasis may require adjuncts to traditional surgical techniques. Fibrin tissue adhesives have broad applications in surgery and are particularly useful when addressing the soft tissue encountered in facial plastic surgery. Beyond hemostasis, tissue adhesion and enhanced wound healing are reported benefits associated with a decrease in operating time, necessity for drains and pressure dressings, and incidence of wound healing complications. These products are clinically accessible to most physicians who perform facial plastic surgery, including skin grafts, flaps, rhytidectomy, and endoscopic forehead lift. PMID- 27267013 TI - Hemostasis in Pediatric Surgery. AB - Hemostasis is an important concept in pediatric otolaryngologic surgery. This article details the considerations the otolaryngologist should take when it comes to clinical evaluation and surgical technique. It begins with the preoperative evaluation, and evolves into the use of different mechanical and chemical methods of operative hemostasis. We detail use of different hemostatic techniques in common pediatric procedures, and finally, we discuss indications for intraoperative and postoperative blood transfusion in pediatric patients if the surgeon encounters significant intraoperative hemorrhage. This paper gives a comprehensive look into the hemostatic considerations for the pediatric patient through the preoperative to postoperative period. PMID- 27267015 TI - Surgical Management of Severe Epistaxis. AB - Many patients with severe epistaxis benefit from endoscopic intervention for control of bleeding. Critical maneuvers to improve endoscopic visualization during surgery include head-of-bed elevation, application of topical vasoconstrictors, and local injection of vasonstrictors. Controlled, hypotensive anesthesia may also decrease intraoperative blood loss and improve visualization during surgery. Intractable posterior epistaxis can be controlled with high rates of success with endoscopic sphenopalatine artery ligation. Although less common, intractable anterior epistaxis may be controlled by anterior ethmoid artery ligation once this artery is identified as the primary source. Less common sources of severe epistaxis are also discussed in this article. PMID- 27267014 TI - Hemostasis in Tonsillectomy. AB - Tonsillectomy is a commonly performed procedure with an accepted risk of posttonsillectomy hemorrhage (PTH) approaching 5%, but catastrophic effects of hemorrhage are exceedingly rare. A variety of surgical techniques and hemostatic agents have been used to reduce the rate of hemorrhage, although none eliminate the risk. Numerous patient, surgical, and postoperative care factors have been studied for an association with PTH. The most consistent risk factors for PTH seem to be patient age and coagulopathies. Surgeon skill and surgical technique are most consistently associated with primary PTH. PMID- 27267016 TI - Treatment of Hereditary Hemorrhagic Telangiectasia-Related Epistaxis. AB - Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an incidence of 1:5000. Recurrent, spontaneous epistaxis is the most common presenting symptom. Severity of epistaxis varies widely, from mild, self-limited nosebleeds to severe, life-threatening nasal hemorrhage. Treatment of HHT-related epistaxis presents a challenge to the otolaryngologist due to the recurrent, persistent nature of epistaxis often requiring multiple treatments. Treatment modalities range from conservative topical therapies to more aggressive surgical treatments. PMID- 27267017 TI - Hemostasis in Endoscopic Sinus Surgery. AB - Intraoperative bleeding during endoscopic sinus surgery poses an additional dimension to an already technically challenging surgical approach because of the narrow sinonasal surgical field, single working hand, and the use of endoscopic instruments. Poor visualization is one of the most important factors that increase the risk of intraoperative complications such as inadvertent injury to major vessels and nerves, and incomplete surgery. This article provide a logical approach to improving the surgical field, minimizing risk of inadvertent vascular injury, and managing intraoperative bleeding. PMID- 27267018 TI - Hemostasis in Skull Base Surgery. AB - Having absolute hemostasis is crucial in skull base surgery, because bleeding decreases visualization and increases the risk of postoperative complications. Achieving hemostasis starts from the preoperative evaluation. A thorough clinical history and routine tests guide the surgeon to minimize bleeding risk preoperatively, and comprehensive study of preoperative images helps the surgeon to predict bleeding risk and to consider preoperative embolization in suitable cases. Many hemostatic agents are available to control intraoperative bleeding; understanding of their indications and properties is crucial to achieve hemostasis. Whether endoscopic or transcranial approach, microsurgical techniques to avoid and control bleeding are the same. PMID- 27267019 TI - Hemostasis in Airway Surgery: Adult and Pediatric. AB - Surgical bleeding is an unlikely, but potentially devastating, event during the surgical management of pediatric and adult laryngotracheal disorders. Therefore, an intimate knowledge of the anatomy of the large vessels coursing in the vicinity of the airway is imperative. Anatomic variants in the position of the inominate artery or the superior thyroid artery can place individuals with these variations at particular risk in these cases. Delayed bleeding from an inominate artery fistula is a particularly devastating complication from open airway surgery. A high index of suspicion is necessary to allow for early identification and aggressive treatment of this potential complication. PMID- 27267020 TI - Hemostasis in Laryngeal Surgery. AB - The larynx is a highly vascularized organ supplied by the superior and inferior laryngeal arteries. Both microphonosurgery and external laryngeal surgery require excellent hemostasis. Topical agents including adrenalin and fibrin-based products as well as surgical instrumentation, such as coagulation devices or in some cases embolization, are in the surgeon's armamentarium and facilitate efficient and successful surgery. PMID- 27267021 TI - Hemostatic Options for Transoral Robotic Surgery of the Pharynx and Base of Tongue. AB - Surgery with transoral robotic surgery (TORS) offers significant advantages compared with traditional open surgical approaches and potentially minimizes the long-term side effects of organ preservation therapy with chemoradiation. Angled telescopes and wristed instruments allow visualization and access to areas of the pharynx that are difficult to reach with line-of-sight instrumentation. Although the application of TORS in head and neck surgery has expanded considerably, there are still only limited data available on the postoperative complications and their management. As further data become available, it is likely that further risk factors and treatment strategies will become available. PMID- 27267022 TI - Thyroidectomy Hemostasis. AB - Total thyroidectomy has significantly changed over the years from a morbid procedure to one that is performed routinely on an outpatient basis. This article reviews the history of thyroid surgery with regard to hemostasis, discusses surgical vascular anatomy, and describes the methods of hemostasis. It compares traditional hemostatic surgical techniques with newer techniques such as the Harmonic Scalpel and LigaSure hand pieces. The use of adjunctive hemostatic agents and indications for a drain in thyroid are discussed. PMID- 27267023 TI - Hemostasis in Otologic and Neurotologic Surgery. AB - Hemostasis is a critical component of otologic and neurotologic surgery. In these surgeries the surgical field is small; thus, even a small amount of bleeding can obstruct the view of critical and extremely small structures. Additionally, relatively large vascular structures traverse the area; if they are encroached on by trauma or disease, bleeding must be controlled within a very small space in a meticulous fashion that does not encroach on structures of the middle ear and mastoid. The authors discuss several hemostatic agents in the middle ear, mastoid, and lateral skull base, highlighting their origins, mechanisms, advantages, and complications. PMID- 27267024 TI - Hemostasis in Orbital Surgery. AB - This article highlights the major vascular supply of the orbit and structures supplied by these vessels. Key anatomic principles are then reviewed as they pertain to endoscopic orbital surgery in order to avoid serious orbital hemorrhages. Next, preoperative planning and patient education are outlined as well as description of orbital compartment syndrome. This is followed by discussion of various techniques for managing orbital hemorrhage in the intraoperative and postoperative setting. PMID- 27267025 TI - Managing Vascular Tumors-Open Approaches. AB - The most common vascular tumors encountered by the otolaryngologist are rare chromaffin cell tumors termed paragangliomas. Within the head and neck region, they commonly arise from the carotid body, vagus nerve (glomus vagale), and jugular vein (glomus jugulare). Other vascular head and neck tumors include sinonasal malignancies, because of proximity to or involvement of the pterygoid plexus as well as the rich vascularity of the sinonasal mucosa; juvenile nasopharyngeal angiofibroma, a vascular tumor of male adolescents; unusual vascular tumors such as hemangiopericytoma; and metastatic renal cell cancer, which has a proclivity for an unusually rich blood supply. PMID- 27267026 TI - Endoscopic Management of Vascular Sinonasal Tumors, Including Angiofibroma. AB - The greatest challenge in the surgical treatment of angiofibromas is dealing with the hypervascularity of these tumors. Staging systems that take into account the vascularity of the tumor may be more prognostic. A variety of treatment strategies are used to deal with the vascularity of angiofibromas, including preoperative embolization, segmentation of the tumor into vascular territories, use of hemostatic tools, and staging of surgery. Even large angiofibromas with intracranial extension and residual vascularity can be successfully managed by a skull base team using endoscopic techniques. PMID- 27267027 TI - Management of Major Vascular Injury: Open. AB - Major blood vessels are in proximity to other vital structures in the neck and base of skull. Infections and tumors of the head and neck can invade vascular structures. Vascular injuries can lead to massive hemorrhage, cerebral ischemia, or stroke. Emergency and definitive management can be challenging. PMID- 27267028 TI - Management of Major Vascular Injury During Endoscopic Endonasal Skull Base Surgery. AB - A major vascular injury is the most feared complication of endoscopic sinus and skull base surgery. Risk factors for vascular injury are discussed, and an algorithm for management of a major vascular injury is presented. A team of surgeons (otolaryngology and neurosurgery) is important for identification and control of a major vascular injury applying basic principles of vascular control. A variety of techniques can be used to control a major injury, including coagulation, a muscle patch, sacrifice of the artery, and angiographic stenting. Immediate and close angiographic follow-up is critical to prevent and manage subsequent complications of vascular injury. PMID- 27267029 TI - Management of Carotid Blowout from Radiation Necrosis. AB - Although the incidence of carotid blowout has decreased with the advent of better reconstructive techniques, it remains a real risk after major head and neck surgery, especially in an irradiated field. A systematic, multidisciplinary approach incorporating appropriate history and physical examination, adequate resuscitation, diagnostic computed tomography, and diagnostic and therapeutic angiography can manage most of these patients in a safe and effective manner. Surgery has a limited role in acute management, although surgical techniques are useful both for prevention of this problem and for wound management after carotid blowout. PMID- 27267030 TI - Endovascular Management of Diseases in Relation to Otolaryngology. AB - Endovascular techniques can be utilized in many common otolaryngologic conditions. Advancements in in these techniques including but not limited to better distal access catheters, new embolization materials and stents allows this to be a relatively safe and successful procedure. Here we highlighted a few related procedures. PMID- 27267031 TI - Education and Training in Hemostasis: Perspectives of the Early Practitioner and Expert Practitioner. AB - Hemorrhagic emergencies in otolaryngology can present significant challenges to the early practitioner. The development of procedural skills, clinical decision making, effective communication strategies, and leadership remain critical to ensuring positive patient outcomes. Procedural task trainers and simulation-based complex scenarios provide safe and effective learning environments for young practitioners to build confidence and develop such skills. This article reviews the principles of managing epistaxis and postoperative neck hematoma geared toward early learners by providing a road map for educators to use in simulation based curriculums. PMID- 27267032 TI - Simulation Training for Vascular Emergencies in Endoscopic Sinus and Skull Base Surgery. AB - Carotid artery injury during endonasal surgery is a feared and potentially catastrophic complication. Simulation training provides the opportunity for a realistic experience with management of major vascular injuries. The sheep model of carotid artery injury reproduces the challenges of dealing with vascular emergencies during endoscopic sinus and skull base surgery, which include working in narrow nasal confines, high-flow/high-pressure vascular injury, and the immediately challenging surgical field. Simulated vascular emergencies allow for research and development; training using various surgical techniques to control the field, including hemostatic products or direct vascular closure techniques; and consequently improved patient care and outcomes. PMID- 27267033 TI - Hemostasis in Otolaryngology-Head and Neck Surgery. PMID- 27267037 TI - Endothelin 1, ADMA and SDMA in pregnancies with obstetric and thrombotic antiphospholipid syndrome. PMID- 27267039 TI - Twisted and tubular silica structures by anionic surfactant fibers encapsulation. AB - Organic molecules imprinting can be used for introducing specific properties and functionalities such as chirality to mesoporous materials. Particularly organic self-assemblies can work as a scaffold for templating inorganic materials such as silica. During recent years chiral imprinting of anionic surfactant for fabrication of twisted rod-like silica structures assisted by co-structuring directing agent were thoroughly investigated. The organic self-assemblies of anionic surfactants can also be used for introducing other shapes in rod-like silica structures. Here we report the formation of amphiphilic N-miristoyl-l alanine self-assemblies in aqueous solution upon stirring and at presence of l arginine. These anionic surfactant self-assemblies form fibers that grow by increasing the stirring duration. The fibers were studied using transmission electron microscopy, infra-red spectroscopy and vibrational circular dichroism. Addition of silica precursor 1,2-bis(triethoxysilyl)ethylene and co-structuring directing agent N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride at different stages of fibers' growth leads to formation of different silica structures. By controlling stirring duration, we obtained twisted tubular silica structures as a result of fibers encapsulation. We decorated these structures with gold nanoparticles by different methods and measured their optical activity. PMID- 27267038 TI - Risk factors for open-angle glaucoma in Nigeria: results from the Nigeria National Blindness and Visual Impairment Survey. AB - BACKGROUND: The glaucoma-specific blindness prevalence in Nigeria (0.7 %, 95 % CI 0.6-0.9 %) among those aged >=40 years is one of the highest ever reported. This study determined the risk factors for open-angle glaucoma (OAG) in adults examined in the Nigeria National Blindness and Visual Impairment Survey. METHODS: A nationally representative sample of 13,591 people aged >=40 years in 305 clusters in Nigeria were examined (response rate 90.4 %) between January 2005 to June 2007. Everyone had logMAR visual acuity measurement, Frequency Doubling Technology (FDT) visual field testing, autorefraction, A-scan biometry and optic disc assessment. Full ocular examination (n = 6397), included Goldmann applanation tonometry. Values for defining glaucoma using International Society of Geographical and Epidemiological Ophthalmology criteria were derived from the study population. Disc images were graded by Moorfields Eye Hospital Reading Centre. Socio-demographic factors (age, gender, ethnicity, literacy and place of residence), ocular parameters (intraocular pressure [IOP], axial length and mean ocular perfusion pressure [MOPP]) and systemic parameters (blood pressure, blood glucose and body mass index [BMI]) were assessed for association with OAG. RESULTS: Thirteen thousand eighty-one (96 %) of 13,591 participants had vertical cup:disc ratio measured in at least one eye. 682 eyes of 462 participants were classified as OAG, with 12,738 controls. In univariate analyses the following were associated with OAG: increasing age, male gender, Igbo and Yoruba ethnic groups, illiteracy, longer axial length, higher IOP, lower MOPP, greater severity of hypertension and low BMI (underweight). In multivariate analysis, increasing age (odds ratio [OR] 1.04, 95 % CI 1.03-1.05), higher IOP (OR 1.22, 95 % CI 1.18 1.25) and Igbo ethnicity (OR 1.73, 95 % CI 1.18-2.56) were independent risk factors for OAG. CONCLUSION: Case detection strategies for OAG should be improved for those aged >=40 years and for ethnic groups most at risk as a public health intervention. PMID- 27267040 TI - Wettability and spontaneous penetration of a water drop into hydrophobic pores. AB - The penetration of a water drop into hydrophobic pores reflects its instability on a porous surface. To understand the mechanism of penetration and to predict the behavior of such a drop, an investigation was conducted through experimental study combined theoretical analysis. Water drops with volumes from 0.5 to 15MUL were examined on Polydimethylsiloxane (PDMS) substrates containing pores of 800MUm and less in diameter. Results showed a critical condition at which a drop starts to penetrate into a certain sized pore. The critical condition presents a parabolic relationship between the volume of a water drop and the size of a hydrophobic pore. This behavior was due to a net force resulting from Laplace pressure, and capillary pressure. This force was found to be affected by the porosity, wetting angle, and there after the critical condition. The finding of this research will be beneficial for future design of structured surfaces. PMID- 27267042 TI - Zirconium/PVA modified flat-sheet PVDF membrane as a cost-effective adsorptive and filtration material: A case study on decontamination of organic arsenic in aqueous solutions. AB - Organic arsenic in waters has been a global concern in drinking water due to its higher toxicity to humans. In this study, a novel zirconium/polyvinyl alcohol (PVA) modified polyvinylidene fluoride (PVDF) membrane was applied to remove organic arsenic from water. The impregnation of zirconium ions within the modified membrane was attributed to the coordination reactions among the zirconium ions, ether and hydroxyl groups. The synthesized membrane worked better at the acidic conditions and achieved the optimal uptake for both monomethylarsonic (MMA) and dimethylarsinic (DMA) at pH 2.0. The adsorption isotherm study demonstrated that the adsorption of both organic arsenic species was controlled by the mono-layer adsorption process; the maximum adsorption capacities for MMA and DMA were 73.04 and 37.53mg/g at pH 2, and 29.78 and 19.03mg/g at pH 7.0, respectively. The presence of humic acid had a negligible impact on the uptake of organic arsenic, whereas varying impacts on the arsenic adsorption were observed due to the presence of coexisting anions such as fluoride, phosphate, carbonate and silicate. A single piece of membrane with a surface area of only 12.56cm(2) could treat 7.5-L MMA and 4.1-L DMA solution with an influent concentration of about 100MUg/L to meet the WHO and USEPA standard of 10MUg/L. Based on the XPS analyses, the ion exchange reaction between chloride ions on the membrane surface and organic arsenic species was responsible for the removal of both MMA and DMA. PMID- 27267041 TI - Facile synthesis of hydroxyapatite/yeast biomass composites and their adsorption behaviors for lead (II). AB - For the first time, the hydroxyapatite (HAp)/yeast biomass composites were successfully synthesized through a facile alkaline ultrasound cavitation method, and used as a novel sorbent for removal of Pb(2+) from aqueous solution. The obtained HAp/yeast biomass composites were characterized by various techniques, including SEM, EDX, XRD, TGA, FTIR, XPS and fluorescence detection, respectively. It was found that the yeast cells were wrapped by the well-dispersed HAp, and more functional groups (such as carboxyl, hydroxyl and amino) on yeast surface were exposed. Also, varying factors that may affect the adsorption efficiency of HAp/yeast biomass composites, such as solution pH, reaction temperature and time, have been carefully investigated respectively. Remarkably, more than 99% of Pb(2+) can be removed by the HAp/yeast biomass composites. Evidence from FTIR and XPS analysis revealed that the higher removal efficiency should be ascribed to the synergetic effect of synthesized HAp and more functional groups exposed on yeast surface. PMID- 27267044 TI - Clinical characteristics and outcomes of spontaneous bacterial peritonitis caused by Enterobacter species versus Escherichia coli: a matched case-control study. AB - BACKGROUND: Enterobacter species are important nosocomial pathogens, and there is growing concern about their ability to develop resistance during antimicrobial therapy. However, few data are available on the clinical characteristics and outcomes of Enterobacter spontaneous bacterial peritonitis (SBP). METHODS: We retrospectively identified all patients with SBP caused by Enterobacter species admitted to a tertiary care hospital between January 1997 and December 2013. Each case was age- and sex-matched with four patients with Escherichia coli SBP. RESULTS: A total of 32 cases with Enterobacter SBP and 128 controls with E. coli SBP were included. Twenty-one (65.6 %) cases and 111 (86.7 %) controls had Child Pugh class C (P = 0.006). Cases were significantly more likely to have hepatocellular carcinoma (65.6 % vs. 37.5 %, P = 0.004) and upper gastrointestinal bleeding (28.1 % vs. 9.4 %, P = 0.005). The initial response to empirical therapy (81.3 % vs. 81.2 %, P = 0.995) and the 30-day mortality (37.5 % vs. 28.9 %, P = 0.35) were not significantly different between the groups. Drug resistance emerged in one case and in no controls (4.3 % [1/23] vs. 0 % [0/98], P = 0.19). CONCLUSIONS: Compared with E. coli SBP, patients with Enterobacter SBP more frequently had hepatocellular carcinoma and upper gastrointestinal bleeding, yet clinical outcomes were comparable. Development of resistance during third generation cephalosporin therapy was infrequent in patients with Enterobacter SBP. PMID- 27267043 TI - The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of insulin resistance but not of beta cell function in a Chinese population with different glucose tolerance status. AB - BACKGROUND: Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was a surrogate marker of IR; however, the relationship of TG/HDL-C with IR might vary by ethnicity. This study aims to investigate whether lipid ratios-TG/HDL-C, cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio, low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (LDL-C/HDL-C)) could be potential clinical markers of insulin resistance (IR) and beta cell function and further to explore the optimal cut-offs in a Chinese population with different levels of glucose tolerance. METHODS: Four hundred seventy-nine subjects without a history of diabetes underwent a 75 g 2 h Oral Glucose Tolerance Test (OGTT). New-onset diabetes (n = 101), pre-diabetes (n = 186), and normal glucose tolerance (n = 192) were screened. IR was defined by HOMA-IR > 2.69. Based on indices (HOMA-beta, early-phase disposition index [DI30], (DeltaIns30/DeltaGlu30)/HOMA-IR and total-phase index [DI120]) that indicated different phases of insulin secretion, the subjects were divided into two groups, and the lower group was defined as having inadequate beta cell compensation. Logistic regression models and accurate estimates of the areas under receiver operating characteristic curves (AUROC) were obtained. RESULTS: In all of the subjects, TG/HDL, TC/HDL-C, LDL-C/HDL-C, and TG were significantly associated with IR. The AUROCs of TG/HDL-C and TG were 0.71 (95 % CI: 0.66-0.75) and 0.71 (95 % CI: 0.65-0.75), respectively. The optimal cut-offs of TG/HDL-C and TG for IR diagnosis were 1.11 and 1.33 mmol/L, respectively. The AUROCs of TC/HDL-C and LDL-C/HDL-C were 0.66 and 0.65, respectively, but they were not acceptable for IR diagnosis. TG/HDL-C,LDL-C/HDL-C and TG were significantly associated with HOMA beta, but AUROCs were less than 0.50; therefore, the lipid ratios could not be predictors of basal beta cell dysfunction. None of the lipid ratios was associated with early-phase insulin secretion. Only TG/HDL-C and TG were significantly correlated with total-phase insulin secretion, but they also were not acceptable predictors of total-phase insulin secretion (0.60 < AUROC < 0.70). CONCLUSIONS: In a Chinese population with different levels of glucose tolerance, TG/HDL-C and TG could be the predictors of IR. The lipid ratios could not be reliable makers of beta cell function in the population. PMID- 27267045 TI - The Essential Role of Drp1 and Its Regulation by S-Nitrosylation of Parkin in Dopaminergic Neurodegeneration: Implications for Parkinson's Disease. AB - AIMS: Dysfunctional regulation of mitochondrial dynamics, which switches the balance to fission, is involved in neurodegeneration in Parkinson's disease (PD). Dynamin-related protein-1 (Drp1), a key regulator of mitochondrial fission, has been attributed recently to such neurodegeneration in PD. However, the machinery that connects Drp1 to the pathophysiology of PD is unclear. RESULTS: We demonstrated that nitric oxide (NO) was overproduced on 1-methyl-4 phenylpyridinium ion (MPP+) treatment, which subsequently engendered S nitrosylation of Parkin (SNO-Parkin), and thus decreased the interaction with Drp1, leading to elevated Drp1 expression. Consistent with this, Drp1 was elevated in the ventral midbrain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD mouse models, a region usually affected by PD. Concomitantly, in a mouse model of MPTP-induced PD, both SNO-Parkin and Drp1 levels were increased, whereas no significant difference in SNO-Drp1 protein levels were found in these mice. In addition, NO stress, induced by MPP+, triggered the phosphorylation of Drp1 Ser616 and caused its subsequent recruitment to the mitochondria. These events create a death-prone environment that contributes to the loss of dopaminergic neurons. INNOVATION: We first showed that SNO-Parkin reduced its ability as a suppressor of Drp1 expression, leading to upregulation of Drp1 in neurotoxin-based PD models, in vitro and in vivo. CONCLUSION: Our results provide a molecular explanation for the contribution of Drp1 to the pathogenesis of sporadic PD. These findings indicate that the SNO-Parkin pathway may be a novel therapeutic target to treat PD. Antioxid. Redox Signal. 25, 609 622. PMID- 27267046 TI - Can solid phase assays be better utilized to measure efficacy of antibody removal therapies? AB - Antibody removal therapies are used for patients with antibody-mediated-rejection or those requiring desensitization to become transplantable. Accurate measurement of antibody levels prior to, and during treatment, are required to choose the best therapeutic approach, and to provide measure of treatment efficacy. Currently, the FDA does not regard solid-phase assays for HLA-antibody identification as a reliable surrogate-marker for treatment efficacy. Serum samples from 40 patients (58 assays; >2200 positive data points) undergoing antibody-removal-therapies were tested as sample-pairs, pre- and post-treatment. MFI values of IgG and C1q single-antigen-bead assays were compared with antibody titer values (serial dilutions). Antibody reduction was tracked and the differences in pre-to-post-treatment values were calculated as delta-reduction of antibody levels. Dynamic patterns of titration studies reduced effects of serum inherent inhibitory factors (prozone-like); eliminated over-saturation limitations, and provided better estimation of antibody-binding strength compared with the other methods. Moreover, delta-reduction of antibody values using titration studies was significantly more uniform compared with either IgG or C1q tests. Analyzing antibody results using only C1q positive or only higher MFI values did not change the overall magnitude of results. Overall, titration studies provided better estimate of responsiveness to treatment and thus can serve as companion to monitoring efficacy of antibody-removal therapies. PMID- 27267047 TI - Discrepancies between selected Pareto optimal plans and final deliverable plans in radiotherapy multi-criteria optimization. AB - Multi-criteria optimization provides decision makers with a range of clinical choices through Pareto plans that can be explored during real time navigation and then converted into deliverable plans. Our study shows that dosimetric differences can arise between the two steps, which could compromise the clinical choices made during navigation. PMID- 27267048 TI - Vaginal dose de-escalation in image guided adaptive brachytherapy for locally advanced cervical cancer. AB - PURPOSE: Vaginal stenosis is a major problem following radiotherapy in cervical cancer. We investigated a new dose planning strategy for vaginal dose de escalation (VDD). MATERIALS AND METHODS: Fifty consecutive locally advanced cervical cancer patients without lower or middle vaginal involvement at diagnosis from 3 institutions were analysed. External beam radiotherapy was combined with MRI-guided brachytherapy. VDD was obtained by decreasing dwell times in ovoid/ring and increasing dwell times in tandem/needles. The aim was to maintain the target dose (D90 of HR-CTV?85Gy EQD2) while reducing the dose to the surface of the vagina to <140% of the physical fractional brachytherapy dose corresponding to a total EQD2 of 85Gy. RESULTS: The mean vaginal loading (ovoid/ring) was reduced from 51% to 33% of the total loading with VDD, which significantly reduced the dose to the vaginal dose points (p<0.001) without compromising the target dose. The dose to the ICRU recto-vaginal point was reduced by a mean of 4+/-4Gy EQD2 (p<0.001), while doses to bladder and rectum (D2cm3) were reduced by 2+/-2Gy and 3+/-2Gy, respectively (p<0.001). CONCLUSIONS: VDD significantly reduces dose to the upper vagina which is expected to result in reduction of vaginal stenosis. PMID- 27267051 TI - Research culture in allied health: a systematic review. AB - Research evidence is required to guide optimal allied health practice and inform policymakers in primary health care. Factors that influence a positive research culture are not fully understood, and nor is the impact of a positive research culture on allied health professionals. The aim of this systematic review was to identify factors that affect allied health research culture and capacity. An extensive search of 11 databases was conducted in June 2015. Studies were included if they were published in English, had full-text availability and reported research findings relating to allied health professions. Study quality was evaluated using the McMaster Critical Review Forms. Fifteen studies were eligible for inclusion. A meta-analysis was not performed because of heterogeneity between studies. Allied health professionals perceive that their individual research skills are lower in comparison to their teams and organisation. Motivators for conducting research for allied health professionals include developing skills, increasing job satisfaction and career advancement. Barriers include a lack of time, limited research skills and other work roles taking priority. Multilayered strategies, such as collaborations with external partners and developing research leadership positions, aimed at addressing barriers and enablers, are important to enhance allied health research culture and capacity. PMID- 27267049 TI - Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR). AB - PURPOSE: To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR). METHODS: We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade ? 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake. RESULTS: Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p < 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV > 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0 2 point model using these 2 variables, 1 point each for SUV > 0.56 or MLD > 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p < 0.001). CONCLUSIONS: Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV > 0.56 and MLD > 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation. PMID- 27267050 TI - KOTMIN13, a Korean herbal medicine alleviates allergic inflammation in vivo and in vitro. AB - BACKGROUND: The ethanol extract of KOTMIN13, composed of Inula japonica Flowers, Trichosanthes kirilowii Semen, Peucedanum praeruptorum Radix, and Allium macrostemon Bulbs, was investigated for its anti-asthmatic and anti-allergic activities. METHODS: The anti-asthmatic effects of KOTMIN13 were evaluated on ovalbumin (OVA)-induced murine asthma model. Anti-allergic properties of KOTMIN13 in bone-marrow derived mast cells (BMMC) and passive cutaneous anaphylaxis (PCA) in vivo were also examined. RESULTS: In asthma model, KOTMIN13 effectively suppressed airway hyperresponsiveness induced by aerosolized methacholine when compared to the levels of OVA-induced mice. KOTMIN13 treatment reduced the total leukocytes, eosinophil percentage, and Th2 cytokines in the bronchoalveolar lavage fluids in OVA-induced mice. The increased levels of eotaxin and Th2 cytokines in the lung as well as serum IgE were decreased by KOTMIN13. The histological analysis shows that the increased inflammatory cell infiltration and mucus secretion were also reduced. In addition, the degranulation and leukotriene C4 production were inhibited in BMMC with IC50 values of 3.9 MUg/ml and 1.7 MUg/ml, respectively. Furthermore, KOTMIN13 treatment attenuated mast-mediated PCA reaction. CONCLUSIONS: These results demonstrate that KOTMIN13 has anti asthmatic and anti-allergic effects in vivo and in vitro models. PMID- 27267052 TI - Commensal-Specific CD4(+) Cells From Patients With Crohn's Disease Have a T Helper 17 Inflammatory Profile. AB - BACKGROUND & AIMS: Crohn's disease (CD) has been associated with an altered immune response to commensal microbiota, mostly based on increased seroreactivity to microbial proteins. Although T cells are believed to contribute to the development of CD, little is known about the antigens involved. We investigated the antigen-specificity of T cells isolated from patients with CD. METHODS: We isolated peripheral blood mononuclear cells from 65 patients with CD and 45 healthy individuals (controls). We investigated T-cell reactivity to commensal microbial antigens using proliferation assays (based on thymidine incorporation and carboxyfluorescein succinimidyl ester dilution). Gene expression patterns were determined using microarray and real-time polymerase chain reaction analyses. Cytokines, chemokines, and antibodies were measured by enzyme-linked immunosorbent assay, flow cytometry, or multiplex cytokine assays. Intestinal crypts were obtained from surgical resection specimens of 7 individuals without inflammatory bowel disease. We examined the effects of commensal-specific CD4(+) T cells on primary intestinal epithelial cells from these samples. RESULTS: The bacterial proteins FlaX, A4-fla2, and YidX increased proliferation of CD4(+) T cells isolated from peripheral blood of patients with CD compared with controls. In blood samples from controls, CD4(+) T cells specific for FlaX, A4-fla2, or YidX had a T-helper (Th)1 phenotype; a larger proportion of CD4(+) T cells specific for these proteins in patients with CD had a Th17 phenotype or produced Th1 and Th17 cytokines. When supernatants collected from commensal-specific CD4(+) T cells from patients with CD were applied to healthy intestinal epithelial cells, the epithelial cells increased the expression of the chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL8 and the CC chemokine ligand 20 (CCL20). CONCLUSIONS: A larger proportion of commensal-specific CD4(+) T cells from patients with CD have a Th17 phenotype or produce Th1 and Th17 cytokines, compared with T cells from controls; this might contribute to intestinal inflammation in patients with CD. These cells might be targeted for treatment of CD. The transcriptional data of commensal-specific CD4(+) T cells from healthy individuals and CD patients have been deposited in the Gene Expression Omnibus at the National Center for Biotechnology Information (accession no: GSE70469). PMID- 27267054 TI - Rh(III)-Catalyzed Oxidative Annulation Leading to Substituted Indolizines by Cleavage of C(sp(2))-H/C(sp(3))-H Bonds. AB - Rhodium(III)-catalyzed oxidative annulation reactions of pyridinium trifluoromethanesulfonate salts with alkynes leading to substituted indolizines by cleavage of C(sp(2))-H/C(sp(3))-H bonds are developed. The starting materials are readily available, and the reactions have a broad substrate scope. This reaction overcomes some drawbacks of the previous indolizine synthetic methods and provides a new efficient route to indolizine derivatives. PMID- 27267053 TI - Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the Veterans Affairs National Health Care System. AB - BACKGROUND & AIMS: We investigated the real-world effectiveness of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) in treatment of different subgroups of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, or 4. METHODS: We performed a retrospective analysis of data from 17,487 patients with HCV infection (13,974 with HCV genotype 1; 2131 with genotype 2; 1237 with genotype 3; and 135 with genotype 4) who began treatment with sofosbuvir (n = 2986), ledipasvir/sofosbuvir (n = 11,327), or PrOD (n = 3174), with or without ribavirin, from January 1, 2014 through June 20, 2015 in the Veterans Affairs health care system. Data through April 15, 2016 were analyzed to assess completion of treatments and sustained virologic response 12 weeks after treatment (SVR12). Mean age of patients was 61 +/- 7 years, 97% were male, 52% were non-Hispanic white, 29% were non-Hispanic black, 32% had a diagnosis of cirrhosis (9.9% with decompensated cirrhosis), 36% had a Fibrosis-4 index score >3.25 (indicator of cirrhosis), and 29% had received prior antiviral treatment. RESULTS: An SVR12 was achieved by 92.8% (95% confidence interval [CI], 92.3%-93.2%) of subjects with HCV genotype 1 infection (no significant difference between ledipasvir/sofosbuvir and PrOD regimens), 86.2% (95% CI, 84.6%-87.7%) of those with genotype 2 infection (treated with sofosbuvir and ribavirin), 74.8% (95% CI, 72.2%-77.3%) of those with genotype 3 infection (77.9% in patients given ledipasvir/sofosbuvir plus ribavirin, 87.0% in patients given sofosbuvir and pegylated-interferon plus ribavirin, and 70.6% of patients given sofosbuvir plus ribavirin), and 89.6% (95% CI 82.8%-93.9%) of those with genotype 4 infection. Among patients with cirrhosis, 90.6% of patients with HCV genotype 1, 77.3% with HCV genotype 2, 65.7% with HCV genotype 3, and 83.9% with HCV genotype 4 achieved an SVR12. Among previously treated patients, 92.6% with genotype 1; 80.2% with genotype 2; 69.2% with genotype 3; and 93.5% with genotype 4 achieved SVR12. Among treatment-naive patients, 92.8% with genotype 1; 88.0% with genotype 2; 77.5% with genotype 3; and 88.3% with genotype 4 achieved SVR12. Eight-week regimens of ledipasvir/sofosbuvir produced an SVR12 in 94.3% of eligible patients with HCV genotype 1 infection; this regimen was underused. CONCLUSIONS: High proportions of patients with HCV infections genotypes 1-4 (ranging from 75% to 93%) in the Veterans Affairs national health care system achieved SVR12, approaching the results reported in clinical trials, especially in patients with genotype 1 infection. An 8-week regimen of ledipasvir/sofosbuvir is effective for eligible patients with HCV genotype 1 infection and could reduce costs. There is substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections. PMID- 27267055 TI - Serum microRNA-196 and microRNA-200 in pancreatic ductal adenocarcinoma of patients with diabetes mellitus. AB - BACKGROUND/OBJECTIVES: Our aim was to compare expressions of 6 microRNAs (miRNAs) in patients with pancreatic ductal adenocarcinoma (PAC) and non-cancer patients, moreover according to the presence or absence of diabetes mellitus. METHODS: Expressions of miRNA-192, -196, -200, -21, -30 and -423 were measured in 77 patients with PAC and 64 non-cancer patients (34 patients with type 2 DM and 30 control persons). 60 patients with PAC (78%) had DM or prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 44 out of them. RESULTS: The expressions of all microRNAs were 1.4-3.7 times higher (significantly) in the PAC group compared to non-cancer patients. No difference was found between PAC diabetic and PAC non-diabetic patients. MicroRNA-200 was significantly higher in PAC patients with significant body weight loss against those without weight loss. Adding miRNA-196 and -200 to the current marker CA 19 9 improved the discriminative ability of the test (compared to CA 19-9 alone). CONCLUSION: MicroRNA-196 and -200 could be used as additional markers in PAC diagnosis. PMID- 27267056 TI - Theoretical approach to local infusion of antibiotics for infected pancreatic necrosis. AB - BACKGROUND/OBJECTIVES: Infected pancreatic necrosis is a major complications of acute pancreatitis. If drainage is required, local administration of antibiotics through transmural nasocystic or percutaneous catheter may allow increasing local antibiotic concentrations. Drug diffusion becomes the main factor influencing local drug tissue penetration. The present study aims at providing the rationale for the design of new research protocols evaluating the efficacy of local antibiotics for infected pancreatic necrosis. METHODS: A review of microbiological data was performed for the most common organisms causing the infection, antibiotics spectrum and minimum inhibitory concentrations (MIC). A search of the physico-chemical properties of antibiotics was performed to calculate the diffusion coefficients. An estimation of the antibiotic concentrations in pancreatic tissue was obtained using a mathematical model. Efficacy factors (EF) were calculated and the stability of the antibiotic solutions were evaluated to optimize the dosing regimen. RESULTS: Piperacillin, vancomycin and metronidazole achieve high concentrations in the surrounding tissue very fast. Imipenem, ceftriaxone, ciprofloxacin, gentamicin, linezolid and cloxacillin achieve intermediate concentration values. Tigecycline, showed the lowest concentration values (<2 mg/L). Calculated EF is highest for piperacillin and imipenem short after administration and near to surface diffusion area (0.5 cm), but EF of imipenem is higher at deeper areas and longer time after administration. CONCLUSIONS: Considering obtained results, some solutions are proposed using saline as diluent and 25 degrees C of temperature during administration. Imipenem has the best theoretical results in empiric local treatment. Linezolid and tigecycline solutions are not recommended. PMID- 27267057 TI - Comparative genomic and transcriptomic analyses of the Fuzhuan brick tea fermentation fungus Aspergillus cristatus. AB - BACKGROUND: Aspergillus cristatus is the dominant fungus involved in the fermentation of Chinese Fuzhuan brick tea. Aspergillus cristatus is a homothallic fungus that undergoes a sexual stage without asexual conidiation when cultured in hypotonic medium. The asexual stage is induced by a high salt concentration, which completely inhibits sexual development. The taxon is therefore appropriate for investigating the mechanisms of asexual and sexual reproduction in fungi. In this study, de novo genome sequencing and analysis of transcriptomes during culture under high- and low-osmolarity conditions were performed. These analyses facilitated investigation of the evolution of mating-type genes, which determine the mode of sexual reproduction, in A. cristatus, the response of the high osmolarity glycerol (HOG) pathway to osmotic stimulation, and the detection of mycotoxins and evaluation of the relationship with the location of the encoding genes. RESULTS: The A. cristatus genome comprised 27.9 Mb and included 68 scaffolds, from which 10,136 protein-coding gene models were predicted. A phylogenetic analysis suggested a considerable phylogenetic distance between A. cristatus and A. nidulans. Comparison of the mating-type gene loci among Aspergillus species indicated that the mode in A. cristatus differs from those in other Aspergillus species. The components of the HOG pathway were conserved in the genome of A. cristatus. Differential gene expression analysis in A. cristatus using RNA-Seq demonstrated that the expression of most genes in the HOG pathway was unaffected by osmotic pressure. No gene clusters associated with the production of carcinogens were detected. CONCLUSIONS: A model of the mating-type locus in A. cristatus is reported for the first time. Aspergillus cristatus has evolved various mechanisms to cope with high osmotic stress. As a fungus associated with Fuzhuan tea, it is considered to be safe under low- and high osmolarity conditions. PMID- 27267058 TI - Alcohol prevention at sporting events: study protocol for a quasi-experimental control group study. AB - BACKGROUND: Alcohol intoxication and overserving of alcohol at sporting events are of great concern, given the relationships between alcohol consumption, public disturbances, and violence. During recent years this matter has been on the agenda for Swedish policymakers, authorities and key stakeholders, with demands that actions be taken. There is promising potential for utilizing an environmental approach to alcohol prevention as a strategy to reduce the level of alcohol intoxication among spectators at sporting events. Examples of prevention strategies may be community mobilization, Responsible Beverage Service training, policy work, and improved controls and sanctions. This paper describes the design of a quasi-experimental control group study to examine the effects of a multi component community-based alcohol intervention at matches in the Swedish Premier Football League. METHODS: A baseline assessment was conducted during 2015 and at least two follow-up assessments will be conducted in 2016 and 2017. The two largest cities in Sweden are included in the study, with Stockholm as the intervention area and Gothenburg as the control area. The setting is Licensed Premises (LP) inside and outside Swedish football arenas, in addition to arena entrances. Spectators are randomly selected and invited to participate in the study by providing a breath alcohol sample as a proxy for Blood Alcohol Concentration (BAC). Actors are hired and trained by an expert panel to act out a standardized scene of severe pseudo-intoxication. Four types of cross-sectional data are generated: (i) BAC levels among >= 4 200 spectators, frequency of alcohol service to pseudo-intoxicated patrons attempting to purchase alcohol at LP (ii) outside the arenas (>=200 attempts) and (iii) inside the arenas (>= 200 attempts), and (iv) frequency of security staff interventions towards pseudo intoxicated patrons attempting to enter the arenas (>= 200 attempts). DISCUSSION: There is an urgent need nationally and internationally to reduce alcohol-related problems at sporting events, and it is essential to test prevention strategies to reduce intoxication levels among spectators. This project makes an important contribution not only to the research community, but also to enabling public health officials, decision-makers, authorities, the general public, and the sports community, to implement appropriate evidence-based strategies. PMID- 27267060 TI - GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression. AB - Although increasing evidence demonstrated that deregulation of mircoRNA-503 (miRNA-503) contributes to tumorigenesis, little is known about the biological role and intrinsic regulatory mechanisms of miR-503 in prostate cancer (PCa). In present study, we found that miR-503 was significantly downregulated in advanced PCa tissues and cell lines. Downregulation of miR-503 was strongly associated with aggressive clinical-pathological features and poor prognosis in PCa patients. Ectopic expression of miR-503 significantly inhibited tumor cells growth, cell migration and invasion in vitro and in vivo. Mechanistic studies revealed that ZNF217 was a direct target downstream target of miR-503. Knockdown of ZNF217 mimicked the tumor-suppressive effects of miR-503 overexpression on PCa invasion, whereas ZNF217 overexpression attenuated the tumor-suppressive function of miR-503. Subsequently, miR-503 further modulated the activation of ZNF217 downstream epithelial-mesenchymal transition (EMT) genes. Besides, we also found that GATA3 directly increased miR-503 expression and thus decreased ZNF217 expression, indicating the involvement of GATA3/miR-503/ZNF217 signaling in EMT process. Collectively, our results demonstrated that GATA3-driven expression of miR-503 inhibits PCa progression by repressing ZNF217 expression, and also implicated the potential application of miR-503 in PCa therapy. PMID- 27267061 TI - A novel role of c-FLIP protein in regulation of ER stress response. AB - Cellular-Flice-like inhibitory protein (c-FLIP) is an apoptosis modulator known to inhibit the extrinsic apoptotic pathway thus blocking Caspase-8 processing in the Death Inducing Signalling Complex (DISC). We previously demonstrated that c FLIP localizes at the endoplasmic reticulum (ER) and that c-FLIP-deficient mouse embryonic fibroblasts (MEFs) display an enlarged ER morphology. In the present study, we have addressed the consequences of c-FLIP ablation in the ER stress response by investigating the effects of pharmacologically-induced ER stress in Wild Type (WT) and c-FLIP-/- MEFs. Surprisingly, c-FLIP-/- MEFs were found to be strikingly more resistant than WT MEFs to ER stress-mediated apoptosis. Analysis of Unfolded Protein Response (UPR) pathways revealed that Pancreatic ER Kinase (PERK) and Inositol-Requiring Enzyme 1 (IRE1) branch signalling is compromised in c-FLIP-/- cells when compared with WT cells. We found that c-FLIP modulates the PERK pathway by interfering with the activity of the serine threonine kinase AKT. Indeed, c-FLIP-/- MEFs display higher levels of active AKT than WT MEFs upon ER stress, while treatment with a specific AKT inhibitor of c-FLIP-/- MEFs subjected to ER stress restores the PERK but not the IRE1 pathway. Importantly, the AKT inhibitor or dominant negative AKT transfection sensitizes c-FLIP-/- cells to ER stress-induced cell death while the expression of a constitutively active AKT reduces WT cells sensitivity to ER stress-induced death. Thus, our results demonstrate that c-FLIP modulation of AKT activity is crucial in controlling PERK signalling and sensitivity to ER stress, and highlight c-FLIP as a novel molecular player in PERK and IRE1-mediated ER stress response. PMID- 27267059 TI - Interleukin-6: an emerging regulator of pathological pain. AB - Interleukin-6 is an inflammatory cytokine with wide-ranging biological effects. It has been widely demonstrated that neuroinflammation plays a critical role in the development of pathological pain. Recently, various pathological pain models have shown elevated expression levels of interleukin-6 and its receptor in the spinal cord and dorsal root ganglia. Additionally, the administration of interleukin-6 could cause mechanical allodynia and thermal hyperalgesia, and an intrathecal injection of anti-interleukin-6 neutralizing antibody alleviated these pain-related behaviors. These studies indicated a pivotal role of interleukin-6 in pathological pain. In this review, we summarize the recent progress in understanding the roles and mechanisms of interleukin-6 in mediating pathological pain associated with bone cancer, peripheral nerve injury, spinal cord injury, chemotherapy-induced peripheral neuropathy, complete Freund's adjuvant injection, and carrageenan injection. Understanding and regulating interleukin-6 could be an interesting lead to novel therapeutic strategies for pathological pain. PMID- 27267062 TI - Fgf regulates dedifferentiation during skeletal muscle regeneration in adult zebrafish. AB - Fibroblast growth factors (Fgfs) regulate critical biological processes such as embryonic development, tissue homeostasis, wound healing, and tissue regeneration. In zebrafish, Fgf signaling plays an important role in the regeneration of the spinal cord, liver, heart, fin, and photoreceptors, although its exact mechanism of action is not fully understood. Utilizing an adult zebrafish extraocular muscle (EOM) regeneration model, we demonstrate that blocking Fgf receptor function using either a chemical inhibitor (SU5402) or a dominant-negative transgenic construct (dnFGFR1a:EGFP) impairs muscle regeneration. Adult zebrafish EOMs regenerate through a myocyte dedifferentiation process, which involves a muscle-to-mesenchyme transition and cell cycle reentry by differentiated myocytes. Blocking Fgf signaling reduced cell proliferation and active caspase 3 levels in the regenerating muscle with no detectable levels of apoptosis, supporting the hypothesis that Fgf signaling is involved in the early steps of dedifferentiation. Fgf signaling in regenerating myocytes involves the MAPK/ERK pathway: inhibition of MEK activity with U0126 mimicked the phenotype of the Fgf receptor inhibition on both muscle regeneration and cell proliferation, and activated ERK (p-ERK) was detected in injured muscles by immunofluorescence and western blot. Interestingly, following injury, ERK2 expression is specifically induced and activated by phosphorylation, suggesting a key role in muscle regeneration. We conclude that the critical early steps of myocyte dedifferentiation in EOM regeneration are dependent on Fgf signaling. PMID- 27267064 TI - Synthesis and antituberculosis activity of the first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol. AB - The first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol moieties were synthesized and evaluated for inhibition activity against Mycobacterium tuberculosis H37Rv. PMID- 27267063 TI - The comparison of glycosphingolipids isolated from an epithelial ovarian cancer cell line and a nontumorigenic epithelial ovarian cell line using MALDI-MS and MALDI-MS/MS. AB - Glycosphingolipids (GSLs) are important biomolecules, which are linked to many diseases such as GSL storage disorders and cancer. Consequently, the expression of GSLs may be altered in ovarian cancer cell lines in comparison to apparently healthy cell lines. Here, differential expressions of GSLs in an epithelial ovarian cancer cell line SKOV3 and a nontumorigenic epithelial ovarian cell line T29 were studied using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and MALDI-MS/MS. The isolation of GSLs from SKOV3 and T29 cell lines was carried out using Folch partition. GSLs were successfully detected by MALDI-MS, and structurally assigned by a comparison of their MALDI-MS/MS fragmentation patterns with MS/MS data found in SimLipid database. Additionally, LIPID MAPS was used to assign GSL ion masses in MALDI-MS spectra. Seventeen neutral GSLs were identified in Folch partition lower (chloroform/methanol) phases originating from both cell lines, while five globo series neutral GSLs were identified only in the Folch partition lower phase of SKOV3 cell line. Several different sialylated GSLs were detected in Folch partition upper (water/methanol) phases of SKOV3 and T29 cell lines. Overall, this study demonstrates the alteration and increased glycosylation of GSLs in an epithelial ovarian cancer cell line in comparison to a nontumorigenic epithelial ovarian cell line. PMID- 27267065 TI - Rapid synthesis of linear homologous oligoarabinofuranosides related to mycobacterial lipoarabinomannan and a neoglycoconjugate thereof. AB - Rapid and simple synthesis of oligosaccharides related to one of the terminal motifs of mycobacterial lipoarabinomannan is described. An array of homologous linear alpha(1 -> 5)-linked oligoarabinofuranosides with 4-(2-chloroethoxy)phenyl aglycon and selectively unprotected 5-OH group at the non-reducing end was obtained by oligomerization of 3-O-benzoyl beta-D-arabinofuranose 1,2,5 orthobenzoate. Subsequent introduction of beta(1 -> 2)-linked arabinofuranose disaccharide moiety by step-wise glycosylation furnished the target oligosaccharides which were conjugated with bovine serum albumin. PMID- 27267066 TI - Structural and binding properties of laminarin revealed by analytical ultracentrifugation and calorimetric analyses. AB - One of the beta-1,3-glucans, laminarin, has been widely used as a substrate for enzymes including endo-1,3-beta-glucanase. To obtain quantitative information about the molecular interaction between laminarin and endo-1,3-beta-glucanase, the structural properties of laminarin should be determined. The results from pioneering work using analytical ultracentrifugation for carbohydrate analysis showed that laminarin from Laminaria digitata predominantly exists as a single chain species with approximately 5% of triple-helical species. Differential scanning calorimetry experiments did not show a peak assignable to the transition from triple-helix to single-chain, supporting the notion that a large proportion of laminarin is the single-chain species. The interaction of laminarin with an inactive variant of endo-1,3-beta-glucanase from Cellulosimicrobium cellulans, E119A, was quantitatively analyzed using isothermal titration calorimetry. The binding was enthalpically driven and the binding affinity was approximately 10(6) M(-1). The results from binding stoichiometric analysis indicated that on average, E119A binds to laminarin in a 2:1 ratio. This seems to be reasonable, because laminarin mainly exists as a monomer, the apparent molecular mass of laminarin is 3.6 kDa, and E119A would have substrate-binding subsites corresponding to 6 glucose units. The analytical ultracentrifugation experiments could detect different complex species of laminarin and endo-1,3-beta-glucanase. PMID- 27267067 TI - Circulating Progenitor Cells Identify Peripheral Arterial Disease in Patients With Coronary Artery Disease. AB - RATIONALE: Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Despite sharing the same risk factors, only 20% to 30% of patients with coronary artery disease (CAD) develop PAD. Decline in the number of bone marrow-derived circulating progenitor cells (PCs) is thought to contribute to the pathogenesis of atherosclerosis. Whether specific changes in PCs differentiate patients with both PAD and CAD from those with CAD alone is unknown. OBJECTIVE: Determine whether differences exist in PCs counts of CAD patients with and without known PAD. METHODS AND RESULTS: 1497 patients (mean age: 65 years; 62% men) with known CAD were identified in the Emory Cardiovascular Biobank. Presence of PAD (n=308) was determined by history, review of medical records, or imaging and was classified as carotid (53%), lower extremity (41%), upper extremity (3%), and aortic disease (33%). Circulating PCs were enumerated by flow cytometry. Patients with CAD and PAD had significantly lower PC counts compared with those with only CAD. In multivariable analysis, a 50% decrease in cluster of differentiation 34 (CD34+) or CD34+/vascular endothelial growth factor receptor-2 (VEGFR2+) counts was associated with a 31% (P=0.032) and 183% (P=0.002) increase in the odds of having PAD, respectively. CD34+ and CD34+/VEGFR2+ counts significantly improved risk prediction metrics for prevalent PAD. Low CD34+/VEGFR2+ counts were associated with a 1.40-fold (95% confidence interval, 1.03-1.91) and a 1.64-fold (95% confidence interval, 1.07 2.50) increases in the risk of mortality and PAD-related events, respectively. CONCLUSIONS: PAD is associated with low CD34+ and CD34+/VEGFR2+ PC counts. Whether low PC counts are useful in screening for PAD needs to be investigated. PMID- 27267069 TI - Uveitis and the Diagnosis of Multiple Sclerosis. PMID- 27267068 TI - Effect of Bone Marrow-Derived Mononuclear Cell Treatment, Early or Late After Acute Myocardial Infarction: Twelve Months CMR and Long-Term Clinical Results. AB - RATIONALE: Intracoronary delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction (AMI). OBJECTIVE: To demonstrate long-term efficacy of BM MNC treatment after AMI. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large AMI in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were either administered 5 to 7 days (early) or 3 to 4 weeks (late) after AMI. Cardiac magnetic resonance imaging was performed at baseline and after 12 months. The current analysis investigates the change from baseline to 12 months in global LV ejection fraction, LV volumes, scar size, and N-terminal pro-brain natriuretic peptide values comparing the 2 treatment groups with control in a linear regression model. Besides the complete case analysis, multiple imputation analysis was performed to address for missing data. Furthermore, the long-term clinical event rate was computed. The absolute change in LV ejection fraction from baseline to 12 months was -1.9+/-9.8% for control (mean+/-SD), -0.9+/-10.5% for the early treatment group, and -0.7+/-10.1% for the late treatment group. The difference between the groups was not significant, both for complete case analysis and multiple imputation analysis. A combined clinical end point occurred equally in all the groups. Overall, 1-year mortality was low (2.25%). CONCLUSIONS: Among patients with AMI and LV dysfunction, treatment with BM-MNC either 5 to 7 days or 3 to 4 weeks after AMI did not improve LV function at 12 months, compared with control. The results are limited by an important drop out rate. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186. PMID- 27267070 TI - Serotype distribution and penicillin-non-susceptibility of Streptococcus pneumoniae causing invasive diseases in Kuwait: A 10-year study of impact of pneumococcal conjugate vaccines. AB - OBJECTIVES: The impact of PCV7 and PCV13 on pneumococcal infections in Kuwait is not known. Therefore we evaluated the impact on pneumococcal serotype distribution and penicillin-non-susceptibility in invasive infections in Kuwait. METHODS: Children < 2 y were given PCV7 from Aug 2006 to Jul 2010 (period I), and PCV13 from Aug 2010 to Jul 2013 (period II) with a pre-vaccination period from Aug 2003 to Jul 2006. Serotype and penicillin-non-susceptibility of blood and cerebrospinal fluid isolates from all ages were determined. RESULTS: In <2 y old children, even with a small number of infections, a drop in PCV7 serotypes was evident after vaccination. For all age groups combined, in the pre-vaccination period, PCV7, PCV13, PCV13 non-PCV7 serotypes and penicillin-non-susceptibility constituted 53.2%, 72.6%, 19.4% and 6.5% of the isolates respectively. PCV7, PCV13 non-PCV7 serotypes and penicillin-non-susceptibility changed to 32.7%, 28.2% and 7.3% (period I) and 6.6%, 22.2% and 8.9% (period II). CONCLUSIONS: Vaccines reduced invasive infections due to PCV7 serotypes. PMID- 27267071 TI - In Situ Generated HypoIodite Activator for the C2 Sulfonylation of Heteroaromatic N-oxides. AB - A mild approach for direct C2 sulfonylation of heteroaromatic N-oxides with sulfonyl hydrazides affording 2-sulfonyl quinolines/pyridines has been developed. A variety of heteroaromatic N-oxides and sulfonyl hydrazides participate effectively in this transformation which uses hypoiodites (generated in situ from NaI and TBHP) as a means of substrate activators. In this reaction, the N-oxide plays a dual role, acting as a traceless directing group as well as a source of oxygen atom. PMID- 27267072 TI - Characterization of therapeutic antibodies and related products by two dimensional liquid chromatography coupled with UV absorbance and mass spectrometric detection. AB - The development of analytical tools for the characterization of large biomolecules is an emerging and rapidly evolving area. This development activity is motivated largely by the current trend involving the increase in development and use of large biomolecules for therapeutic uses. Given the inherent complexity of these biomolecules, which arises from their sheer size and possibilities for chemical modification as well as changes over time (e.g., through modification in solution, aggregation), two-dimensional liquid chromatography (2D-LC) has attracted considerable interest as an analytical tool to address the challenges faced in characterizing these materials. The immediate potential benefits of 2D LC over conventional one-dimensional liquid chromatography in this context include: (1) higher overall resolving power; (2) complementary information gained from two dimensions of separation in a single analysis; and (3) enabling indirect coupling of separation modes that are inherently incompatible with mass spectrometric (MS) detection (e.g., ion-exchange, because of high-salt eluents) to MS through a more compatible second dimension separation such as reversed phase LC. In this review we summarize the work in this area, most of which has occurred in the past five years. Although the future is bright for further development in this area, some challenges have already been addressed through new 2D-LC methods. These include: (1) deep characterization of monoclonal antibodies to understand charge heterogeneity, glycosylation patterns, and other modifications; (2) characterization of antibody-drug conjugates to understand the extent and localization of small molecule conjugation; (3) detailed study of excipients in protein drug formulations; and (4) detection of host-cell proteins on biotherapeutic molecule preparations. We fully expect that in the near future we will see this list expanded, and that continued development will lead to methods with further improved performance metrics. PMID- 27267073 TI - A new anti-human Fc method to capture and analyze ADCs for characterization of drug distribution and the drug-to-antibody ratio in serum from pre-clinical species. AB - Antibody-drug conjugates (ADCs) are becoming a major class of oncology therapeutics. They combine monoclonal antibody specificity for over-expressed tumor antigens and the high cytoxicity of small molecular drugs (SMDs) and can therefore selectively kill tumor cells while minimizing toxicity to normal cells. Nevertheless, the premature deconjugation of ADCs in the circulation may trigger off target toxicity in patients. The released free drug level must be low in circulation for an extended period of time as well as the de-conjugation rate to ensure an acceptable therapeutic window. As a result, the assessment of the stability of the linker between payload and mAb in the systemic circulation is of paramount importance before entering in clinical trial. Here we report a new universal method to immunocapture and analyze by LC-MS the stability and distribution of ADCs in sera from relevant preclinical species (mouse, rat and cynomolgus monkey). Furthermore we demonstrated that this workflow can be applied to both ADCs with cleavable and non cleavable linkers. Last but not least, the results obtained in cynomolgus serum using immunoprecipitation and LC-MS analysis were cross validated using an ELISA orthogonal method. As the ligand used for immunoprecipitation is targeting the Fc part of mAb (CaptureSelectTM Human IgG-Fc PK Biotin), this protocol can be applied to analyze the stability of virtually all ADCs in sera for preclinical studies without the need to prepare specific molecular tools. PMID- 27267074 TI - Quantifying Individual Brain Connectivity with Functional Principal Component Analysis for Networks. AB - In typical functional connectivity studies, connections between voxels or regions in the brain are represented as edges in a network. Networks for different subjects are constructed at a given graph density and are summarized by some network measure such as path length. Examining these summary measures for many density values yields samples of connectivity curves, one for each individual. This has led to the adoption of basic tools of functional data analysis, most commonly to compare control and disease groups through the average curves in each group. Such group differences, however, neglect the variability in the sample of connectivity curves. In this article, the use of functional principal component analysis (FPCA) is demonstrated to enrich functional connectivity studies by providing increased power and flexibility for statistical inference. Specifically, individual connectivity curves are related to individual characteristics such as age and measures of cognitive function, thus providing a tool to relate brain connectivity with these variables at the individual level. This individual level analysis opens a new perspective that goes beyond previous group level comparisons. Using a large data set of resting-state functional magnetic resonance imaging scans, relationships between connectivity and two measures of cognitive function-episodic memory and executive function-were investigated. The group-based approach was implemented by dichotomizing the continuous cognitive variable and testing for group differences, resulting in no statistically significant findings. To demonstrate the new approach, FPCA was implemented, followed by linear regression models with cognitive scores as responses, identifying significant associations of connectivity in the right middle temporal region with both cognitive scores. PMID- 27267075 TI - Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer. AB - BACKGROUND: Androgen insensitivity syndrome (AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor (AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer (CRC) have been described. CASE PRESENTATION: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a microRNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers. CONCLUSIONS: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis. PMID- 27267076 TI - Serum 8-hydroxy-2-deoxyguanosine as a marker of DNA oxidative damage in horses with recurrent airway obstruction. AB - BACKGROUND: It has been reported that equine recurrent airway obstruction (RAO) is a state of oxidative stress. Oxidant-antioxidant imbalance is known to increase the conversion of deoxyguanosine to 8-hydroxy-2-deoxyguanosine (8-OHdG) in DNA. 8-OHdG can easily be measured using ELISA tests in serum or urine samples. In this study, we analysed serum 8-OHdG levels in horses with recurrent airway obstruction and in healthy controls. RESULTS: The study material consisted of seven healthy horses and seven horses with symptomatic RAO. All horses were exposed to moldy hay and straw for 48 h to induce clinical exacerbation of RAO. The serum 8-OHdG levels were determined using the ELISA Highly Sensitive 8-OHdG kit. The difference between the levels of 8-OHdG in healthy and RAO-affected horses was significant. The median level of 8-OHdG was 0.044 ng/ml in the healthy controls versus 0.498 ng/ml in RAO horses (P = 0.0021). CONCLUSIONS: The results of the study strongly suggest that DNA damage coexists in the course of equine RAO. We therefore propose that future research should aim at the development of new drugs that target pro-inflammatory molecules, since DNA damage appears to be the result of chronic inflammation. PMID- 27267077 TI - End-of-Life Care: Whose Decision Is It Anyway? A Case Study in an Assisted Living Facility. PMID- 27267078 TI - 101 Solution-focused questions for help with depression. PMID- 27267079 TI - Paracoccusacridae sp. nov., isolated from the insect Acrida cinerea living in deserted cropland. AB - A Gram-stain-negative, aerobic, rod-shaped, non-motile bacterial strain, designated SCU-M53T, was isolated from the insect Acrida cinerea. Phylogenetic analysis on the basis of 16S rRNA gene sequences showed that strain SCU-M53T belonged to the genus Paracoccus, having Paracoccus chinensisNBRC 104937T (97.04 % 16S rRNA gene sequence similarity) and Paracoccus niistensis KCTC 22789T (96.70 %) as the most closely related phylogenetic neighbours. Growth occurred at 10-40 degrees C (optimum 25-30 degrees C), pH 5.0-10.0 (optimum pH 6.5-7.5) and with 0 4 % (w/v) NaCl (optimum 0-1 % NaCl). The fatty acids of strain SCU-M53T were C18 : 1omega7c, C18 : 0, C16 : 0, C14 : 0 3-OH, C14 : 0 and C10 : 0 3-OH. The polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, an unknown aminolipid, two unknown phospholipids and two unknown lipids. The isoprenoid quinone was ubiquinone-10. The DNA G+C content was 60.6 mol%. Strain SCU-M53T exhibited 36.5 and 28.6 % DNA-DNA relatedness to P. chinensis NBRC 104937T and P. niistensis KCTC 22789T, respectively. According to these results, strain SCU-M53T represents a novel species of the genus Paracoccus, for which the name Paracoccus acridae sp. nov. is proposed. The type strain is SCU-M53T (=KCTC 42932T=CGMCC 1.15419T). PMID- 27267080 TI - Changes in Thyroid Hormone Levels Within the Normal and/or Subclinical Hyper- or Hypothyroid Range Do Not Affect Circulating Irisin Levels in Humans. AB - BACKGROUND: Both thyroid hormones and irisin increase energy expenditure and induce browning of adipose tissue. However, irisin physiology and regulation remain largely unknown, and existing data are mainly derived from observational studies. In this study, we aimed to elucidate whether changes in thyroid-axis hormones alter circulating irisin levels in humans, thereby exerting a direct downstream effect on serum irisin. SUBJECTS AND METHODS: Samples from a cross sectional evaluation and two interventions were utilized, including patients who had previously undergone thyroidectomy. In the cross-sectional study, 96 consecutively enrolled subjects were divided into a euthyroid group and a subclinical hyperthyroid group, according to their serum thyrotropin (TSH) levels (TSH cutoff 0.3 mIU/L). In interventional study A, 34 patients who had undergone thyroidectomy due to thyroid cancer were withdrawn from their thyroxine replacement treatment for five weeks. In interventional study B, 13 patients underwent a recombinant human TSH stimulation protocol, and blood samples were drawn at baseline, day 3 (i.e., at least 24 hours after the second intramuscular injection), day 5, and day 10. RESULTS: Irisin concentrations were not associated with thyroid-axis hormones (i.e., TSH, free thyroxine, and free triiodiothyronine) cross-sectionally in either the overall cohort or in the euthyroid and/or subclinical hyperthyroid subgroups (p > 0.05). There was no significant difference between euthyroid and subclinical hyperthyroid subjects (p = 0.60). Levothyroxine withdrawal did not result in any changes in irisin concentrations (p = 0.33). Recombinant human TSH stimulation did not induce any significant changes in circulating irisin (p = 0.60). CONCLUSIONS: Changes in thyroid-axis hormone levels within the physiological or supraphysiological range do not affect circulating irisin levels in humans. Therefore, their metabolic effects are most likely independent of each other. Other regulators of irisin levels should be identified in the future. PMID- 27267081 TI - Erlotinib for Japanese patients with activating EGFR mutation-positive non-small cell lung cancer: combined analyses from two Phase II studies. AB - AIMS: We evaluated the efficacy and safety of erlotinib, and patient characteristics affecting progression-free survival (PFS), by analyzing data from two Phase II studies of first-line erlotinib in activating EGFR mutation-positive non-small-cell lung cancer. METHODS: Data were combined from patients who received first-line erlotinib monotherapy in JO22903 (single-arm study; JapicCTI 101085) and JO25567 (randomized study; JapicCTI-111390). RESULTS: Median PFS was 10.9 months in efficacy-evaluable patients (n = 177). Major adverse events were dermatologic; no new safety signals were observed. Baseline pleural/cardiac effusion notably affected PFS (yes median 8.0 months vs no median 15.3 months) as confirmed in multivariate analysis (hazard ratio: 0.38; 95% CI: 0.25-0.58). CONCLUSION: Efficacy and safety of erlotinib monotherapy were consistent with previous studies. Baseline pleural/pericardial effusion was associated with shorter PFS. PMID- 27267082 TI - An electromyographic study of the effect of hand grip sizes on forearm muscle activity and golf performance. AB - The study describes the differences in surface electromyography (EMG) activity of two forearm muscles in the lead and trail arm at specific phases of the golf swing using a 7-iron with three different grip sizes among amateur and professional golfers. Fifteen right-handed male golfers performed five golf swings using golf clubs with three different grip sizes. Surface EMG was used to measure muscle activity of the extensor carpi radialis brevis (ECRB) and flexor digitorum superficialis (FDS) on both forearms. There were no significant differences in forearm muscle activity when using the three golf grips within the group of 15 golfers (p > 0.05). When using the undersize grip, club head speed significantly increased (p = 0.044). During the backswing and downswing phases, amateurs produced significantly greater forearm muscle activity with all three grip sizes (p < 0.05). In conclusion, forearm muscle activity is not affected by grip sizes. However, club head speed increases when using undersize grips. PMID- 27267083 TI - Early Onset Scoliosis-A Comprehensive Guide from the Oxford Meetings (2015). PMID- 27267084 TI - Synthesis of Amphiphilic Poly(beta-amino ester) for Efficiently Minicircle DNA Delivery in Vivo. AB - Minicircle DNA (mcDNA) is a kind of enhanced nonviral DNA vector with excellent profiles in biosafety and transgene expression. Herein, we reported a novel amphiphilic polymer comprising polyethylenimine(PEI) modified Poly(beta-amino ester) PEI-PBAE(C16) for efficient mcDNA delivery in vivo. The synthesized polymer could condense mcDNA into nanoscaled structure and exhibited efficient gene transfection ability without detectable cytotoxicity. Importantly, when injected into mouse intraperitoneally, these PEI-PBAE(C16) nanocomplexes were able to result in high level of trangene expression which lasted at least 72 h. Overall, these results demonstrated the PEI-PBAE(C16) can mediate effective and safe gene delivery in vivo with clinical application potential. PMID- 27267085 TI - Culture scale-up and immobilisation of a mixed methanotrophic consortium for methane remediation in pilot-scale bio-filters. AB - Robust methanotrophic consortia for methane (CH4) remediation and by-product development are presently not readily available for industrial use. In this study, a mixed methanotrophic consortium (MMC), sequentially enriched from a marine sediment, was assessed for CH4 removal efficiency and potential biomass generated by-product development. Suitable packing material for bio-filters to support MMC biofilm establishment and growth was also evaluated. The enriched MMC removed ~7-13% CH4 under a very high gas flow rate (2.5 L min-1; 20-25% CH4) in continuous-stirred tank reactors (~10 L working volume) and the biomass contained long-chain fatty acids (i.e. C16 and C18). Cultivation of the MMC on plastic bio balls abated ~95-97% CH4 in pilot-scale non-sterile outdoor-operated bio-filters (0.1 L min-1; 1% CH4). Contamination by cyanobacteria had beneficial effects on treating low-level CH4, by providing additional oxygen for methane oxidation by MMC, suggesting that the co-cultivation of MMC with cyanobacterial mats does not interfere with and may actually be beneficial for remediation of CH4 and CO2 at industrial scale. PMID- 27267086 TI - Report calls for bold action to prevent early deaths. PMID- 27267087 TI - Protein Conformational Flexibility Enables the Formation of Dense Liquid Clusters: Tests Using Solution Shear. AB - According to recently proposed two-step nucleation mechanisms, crystal nuclei form within preexisting dense liquid clusters. Clusters with radii about 100 nm, which capture from 10(-7) to 10(-3) of the total protein, have been observed with numerous proteins and shown to host crystal nucleation. Theories aiming to understand the mesoscopic size and small protein fraction held in the clusters have proposed that in solutions of single-chain proteins, the clusters consist of partially misfolded protein molecules. To test this conjecture, we perturb the protein conformation by shearing solutions of the protein lysozyme. We demonstrate that shear rates greater than a threshold applied for longer than 1 h reduce the volume of the cluster population. The likely mechanism of the observed response involves enhanced partial unfolding of lysozyme molecules, which exposes hydrophobic surfaces between the constituent domains to the aqueous solution. PMID- 27267088 TI - Factor Analysis of the MSVT, NV-MSVT, and RBANS Memory Subtests. AB - OBJECTIVE: The current investigation sought to define the relationship between established performance validity tests and measures of memory via a factor analytic strategy first published by Heyanka, Thaler, Linck, Pastorek, Miller, Romesser, & Sim (2015). A Factor analytic approach to the validation of the Word Memory Test and Test of Memory Malingering as measures of effort and not memory. Archives of Clinical Neuropsychology, 30, 369-376. METHOD: The full range of Medical Symptom Validity Test (MSVT) and Non-Verbal Medical Symptom Validity Test (NV-MSVT) subtests were factor analyzed with the memory scales of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in a sample of 346 service members with a history of concussion. RESULTS: A two-factor solution was extracted with the MSVT and NV-MSVT effort and paired associate subtests loading on one factor and the RBANS subtests loading on a second factor. CONCLUSIONS: Results support the conclusion that the effort subtests of the MSVT and NV-MSVT tap a different construct from established memory measures. PMID- 27267089 TI - High Resistivity Lipid Bilayers Assembled on Polyelectrolyte Multilayer Cushions: An Impedance Study. AB - Supported membranes on top of polymer cushions are interesting models of biomembranes as cell membranes are supported on a polymer network of proteins and sugars. In this work lipid vesicles formed by a mixture of 30% 1,2-dioleoyl-sn glycero-3-phosphocholine (DOPC) and 70% 1,2-dioleoyl-sn-glycero-3-phospho-l serine (DOPS) are assembled on top of a polyelectrolyte multilayer (PEM) cushion of poly(allylamine hydrochloride) (PAH) and poly(styrene sodium sulfonate) (PSS). The assembly results in the formation of a bilayer on top of the PEM as proven by means of the quartz crystal microbalance with dissipation technique (QCM-D) and by cryo-transmission electron microscopy (cryo-TEM). The electrical properties of the bilayer are studied by electrochemical impedance spectroscopy (EIS). The bilayer supported on the PEMs shows a high resistance, on the order of 10(7) Omega cm(2), which is indicative of a continuous, dense bilayer. Such resistance is comparable with the resistance of black lipid membranes. This is the first time that such values are obtained for lipid bilayers supported on PEMs. The assembly of polyelectrolytes on top of a lipid bilayer decreases the resistance of the bilayer up to 2 orders of magnitude. The assembly of the polyelectrolytes on the lipids induces defects or pores in the bilayer which in turn prompts a decrease in the measured resistance. PMID- 27267090 TI - Suboptimal decision making by children with ADHD in the face of risk: Poor risk adjustment and delay aversion rather than general proneness to taking risks. AB - OBJECTIVE: Suboptimal decision making in the face of risk (DMR) in children with attention-deficit hyperactivity disorder (ADHD) may be mediated by deficits in a number of different neuropsychological processes. We investigated DMR in children with ADHD using the Cambridge Gambling Task (CGT) to distinguish difficulties in adjusting to changing probabilities of choice outcomes (so-called risk adjustment) from general risk proneness, and to distinguish these 2 processes from delay aversion (the tendency to choose the least delayed option) and impairments in the ability to reflect on choice options. Based on previous research, we predicted that suboptimal performance on this task in children with ADHD would be primarily relate to problems with risk adjustment and delay aversion rather than general risk proneness. METHOD: Drug naive children with ADHD (n = 36), 8 to 12 years, and an age-matched group of typically developing children (n = 34) performed the CGT. RESULTS: As predicted, children with ADHD were not more prone to making risky choices (i.e., risk proneness). However, they had difficulty adjusting to changing risk levels and were more delay aversive with these 2 effects being correlated. CONCLUSIONS: Our findings add to the growing body of evidence that children with ADHD do not favor risk taking per se when performing gambling tasks, but rather may lack the cognitive skills or motivational style to appraise changing patterns of risk effectively. (PsycINFO Database Record PMID- 27267091 TI - Coronary Care Unit to Cardiac Intensive Care Unit: Acute Medical Cardiac Care Adapting With the Times. PMID- 27267092 TI - Angioinvasive lymphomatoid papulosis (type E): a first Japanese case. PMID- 27267093 TI - Practice pearls in the management of lung cancer in the elderly. AB - Lung cancer is a disease that afflicts the elderly. It is a leading cause of cancer mortality worldwide. Treatment of lung cancer which was predominantly combination chemotherapy was initially thought to be too toxic for older patients with cancer due to their frail state. However a number of recent studies have shown that this is not necessarily true and many elderly can actually tolerate combination chemotherapy and derive just as much benefit from it as younger patients with lung cancer do. More recently it has been found that a significant proportion of lung cancer patients have tumors that harbor mutations that are targetable by molecularly targeted therapy (MTT). These targeted therapies have a much better tolerated side effect profile, hence have been used in elderly patient with lung cancer with great success. A new generation of drugs called immune checkpoint inhibitors have now come into the fray with exciting results in the second line treatment of lung cancer with a low side effect profile. A key element in deciding whether an elderly patient with lung cancer can tolerate treatment involves a detailed assessment using the comprehensive geriatric assessment (CGA). A number of CGA and clinical factors have also been found to be able to predict chemotherapy associated toxicity. This review of lung cancer in the elderly was part of a lecture on "Practice pearls in the management of lung cancer in the elderly" presented at the SIOG Annual Meeting in Prague in November 2015. PMID- 27267094 TI - Problems with balance and binocular visual dysfunction are associated with post stroke fatigue. AB - BACKGROUND: Fatigue after stroke is hard to define and measure and how it is associated with other complications after stroke still needs to be explored. These issues are relevant in stroke rehabilitation and in the patient's daily life. OBJECTIVE: To investigate fatigue after stroke and its relation to balance, gait, and Binocular Visual Dysfunction (BVD). METHODS: Adults with stroke (n = 29, age 18-67 years) were tested with the Modified Fatigue Impact Scale (MFIS), objective and subjective BVD measures, Balance Evaluation Systems Test, Ten Meter Walk Test, and a Health-Related Quality of Life questionnaire, before and after a four-month intervention program and at three- and six-month follow-ups. We used principle component analysis to extract underlying factors of MFIS. Associations between MFIS factors and patient characteristics were analyzed by repeated measures ANOVA. The associations between MFIS factors and physical measures were assessed using pairwise correlations. RESULTS: Three components were extracted from the MFIS, explaining 71% of variance: Cognitive fatigue, Physical fatigue and Arousal. We found that women register higher MFIS scores than men. There was a strong association between the level of Cognitive and Physical Fatigue and BVD, between Arousal and balance and dizziness, and between Cognitive Fatigue and gait. CONCLUSION: The three extracted components of MFIS proved clinically informative. The arousal component revealed particularly interesting results in studying fatigue. The correlation analysis shown at this component differs from cognitive and physical fatigue and describes another aspect of PSF, important in future treatment and research. PMID- 27267104 TI - Stimulus size mediates Gestalt processes in object perception - evidence from simultanagnosia. AB - Simultanagnosia caused by posterior temporo-parietal brain damage is characterized through an inability to recognize a global Gestalt from an arrangement of single objects while perception of single objects appears widely intact. We asked whether recognition of single objects in simultanagnosia is still intact if objects are really large, i.e. if they exceed the size of a usual computer screen. Single objects were presented in three different sizes: 'regular', 'medium', and 'large'. Simultanagnosia patients demonstrated a decrease of recognition performance with increasing object size; recognition of 'large' objects was significantly impaired while perception of 'regular' sized objects was unaffected. The results argue against the traditional view of preserved recognition of single objects in simultanagnosia. They provide evidence for a more general perceptual impairment that emerges irrespective of presenting single or multiple objects, but whenever the visual system has to assemble information over larger spatial distances or other demanding viewing conditions. It appears that perception of large single objects requires intact abilities of dorsal Gestalt processing, in addition to regular functions of ventral object recognition. PMID- 27267105 TI - Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials. AB - Renal impairment (RI) is a major comorbidity in patients with multiple myeloma (MM). Here we present the pooled safety and efficacy analysis of three clinical trials (MM-002, MM-003, and MM-010) of pomalidomide + low-dose dexamethasone (POM + LoDEX) in patients with moderate RI (creatinine clearance [CrCl] >= 30 to <60 mL/min) and without RI (>= 60 mL/min). Trial protocols were approved by the institutional review board of each site involved. Patients with RI were older than patients without RI, although other baseline characteristics were similar. The dosing and safety profile of POM + LoDEX was similar across RI subgroups. Median overall response rate, progression-free survival, time to progression, and duration of response were not significantly different between RI subgroups. However, patients with vs. without RI had significantly shorter median overall survival (10.5 vs. 14.0 months, respectively; p = .004). This analysis demonstrates that POM + LoDEX is a safe and effective treatment for patients with moderate RI. The trials were registered at ClinicalTrials.gov as NCT00833833 (MM 002), NCT01311687 (MM-003), and NCT01712789 (MM-010) and at EudraCT as 2010 019820-30 (MM-003) and 2012-001888-78 (MM-010). PMID- 27267106 TI - Comparative efficacy of selective serotonin reuptake inhibitors (SSRI) in treating major depressive disorder: a protocol for network meta-analysis of randomised controlled trials. AB - INTRODUCTION: There have been inconsistent findings from randomised controlled trials (RCTs) and systematic reviews on the efficacies of selective serotonin reuptake inhibitors (SSRIs) as the first-line treatment of major depressive disorder (MDD). Besides inconsistencies among randomised controlled trials (RCTs), their risks of bias and evidence grading have seldom been evaluated in meta-analysis. This study aims to compare the efficacy of SSRIs by conducting a Bayesian network meta-analysis, which will be the most comprehensive evaluation of evidence to resolve the inconsistency among previous studies. METHODS AND ANALYSES: SSRIs including citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline and vilazodone have been selected. Systematic database searching and screening will be conducted for the RCTs on drug treatment of patients with MDD according to pre-specified search strategies and selection criteria. PubMed, the Cochrane Library, EMBASE, ScienceDirect, the US Food and Drug Administration Website, ClinicalTrial.gov and WHO Clinical Trials will be searched. Outcome data including Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) from eligible RCTs will be extracted. The outcomes will be analysed as ORs and mean differences under a random-effects model. A Bayesian network meta analysis will be conducted with WinBUGS software, to compare the efficacies of SSRIs. Subgroup and sensitivity analysis will be performed to explain the study heterogeneity and evaluate the robustness of the results. Meta-regression analysis will be conducted to determine the possible factors affecting the efficacy outcomes. The Cochrane risk of bias assessment tool will be used to assess the RCT quality, and the Grading of Recommendation, Assessment, Development and Evaluation will be used to assess the strength of evidence from the meta-analysis. ETHICS AND DISSEMINATION: No ethical approval is required because this study includes neither confidential personal patient data nor interventions with patients. PROTOCOL REGISTRATION NUMBER: CRD42015024879. PMID- 27267108 TI - Systematic review of the cost-effectiveness of implementing guidelines on low back pain management in primary care: is transferability to other countries possible? AB - OBJECTIVE: The primary aim is to identify, summarise and quality assess the available literature on the cost-effectiveness of implementing low back pain guidelines in primary care. The secondary aim is to assess the transferability of the results to determine whether the identified studies can be included in a comparison with a Danish implementation study to establish which strategy procures most value for money. DESIGN: Systematic review. DATA SOURCES: The search was conducted in Embase, PubMed, Cochrane Library, NHS Economic Evaluation Database, Scopus, CINAHL and EconLit. No restrictions were made concerning language, year of publication or publication type. The bibliographies of the included studies were searched for any studies not captured in the literature search. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: To be included, a study must be: (1) based on a randomised controlled trial comparing implementation strategies, (2) the guideline must concern treatment of low back pain in primary care and (3) the economic evaluation should contain primary data on cost and cost effectiveness. RESULTS: The title and abstract were assessed for 308 studies; of these, three studies were found eligible for inclusion. The Consensus Health Economic Criteria (CHEC) list showed that the 3 studies were of moderate methodological quality while application of Welte's model showed that cost results from two studies could, with adjustments, be transferred to a Danish setting. It was questionable whether the associated effects could be transferred. CONCLUSIONS: Despite the resemblance of the implementation strategies, the 3 studies report conflicting results on cost-effectiveness. This review showed that transferring the results from the identified studies is not straightforward and underlines the importance of transparent reporting. Future research should focus on transferability of effects, for example, development of a supplement to Welte's model. PMID- 27267107 TI - Association between different risk factors and vascular accelerated ageing (EVA study): study protocol for a cross-sectional, descriptive observational study. AB - INTRODUCTION: The process of population ageing that is occurring in developed societies represents a major challenge for the health system. The aim of this study is to analyse factors that have an influence on early vascular ageing (EVA), estimated by carotid-femoral pulse wave velocity (cf-PWV) and Cardio Ankle Vascular Index (CAVI), and to determine differences by gender in a Spanish population. METHODS AND ANALYSIS: An observational, descriptive, cross-sectional study. STUDY POPULATION: From the population assigned to the participating healthcare centres, a cluster random sampling stratified by age and gender will be performed to obtain 500 participants aged between 35 and 75. Those who meet the inclusion criteria and give written informed consent will be included in the study. MEASUREMENTS: Main dependent variables: cf-PWV determined using the SphygmoCor System and CAVI estimated using VASERA. Secondary dependent variables: telomere length, carotid intima-media thickness, central and peripheral augmentation index, ankle-brachial pulse wave velocity, ankle-brachial index, retinal arteriovenous index, and renal and cardiac organ damage. INDEPENDENT VARIABLES: lifestyles (physical activity, adherence to the Mediterranean diet, alcohol and tobacco consumption); psychological factors (depression, anxiety and chronic stress); inflammatory factors and oxidative stress. ETHICS AND DISSEMINATION: The study has been approved by the clinical research ethics committee of the healthcare area of Salamanca. All study participants will sign an informed consent form agreeing to participate in the study in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow the understanding of the relationship of the different influencing factors and their relative weight in the development of EVA. At least 5 publications in first-quartile scientific journals are planned. TRIAL REGISTRATION NUMBER: NCT02623894; Pre-results. PMID- 27267109 TI - Physiotherapy informed by Acceptance and Commitment Therapy (PACT): protocol for a randomised controlled trial of PACT versus usual physiotherapy care for adults with chronic low back pain. AB - INTRODUCTION: Chronic low back pain (CLBP) is a common condition and source of significant suffering, disability and healthcare costs. Current physiotherapy treatment is moderately effective. Combining theory-based psychological methods with physiotherapy could improve outcomes for people with CLBP. The primary aim of this randomised controlled trial (RCT) is to evaluate the efficacy of Physiotherapy informed by Acceptance and Commitment Therapy (PACT) on functioning in patients with CLBP. METHODS AND ANALYSIS: The PACT trial is a two-armed, parallel-group, multicentre RCT to assess the efficacy of PACT in comparison with usual physiotherapy care (UC). 240 patients referred to physiotherapy with CLBP will be recruited from three National Health Service (NHS) hospitals trusts. Inclusion criteria are: age >=18 years, CLBP >=12-week duration, scoring >=3 points on the Roland-Morris Disability Questionnaire (RMDQ) and adequate understanding of spoken and written English to participate. Patients will be randomised to PACT or UC (120 per arm stratified by centre) by an independent randomisation service and followed up at 3 and 12 months post randomisation. The sample size of 240 will provide adequate power to detect a standardised mean difference of 0.40 in the primary outcome (RMDQ; 5% significance, 80% power) assuming attrition of 20%. Analysis will be by intention to treat conducted by the trial statistician, blind to treatment group, following a prespecified analysis plan. Estimates of treatment effect at the follow-up assessments will use an intention-to-treat framework, implemented using a linear mixed-effects model. ETHICS AND DISSEMINATION: This trial has full ethical approval (14/SC/0277). It will be disseminated via peer-reviewed publications and conference presentations. The results will enable clinicians, patients and health service managers to make informed decisions regarding the efficacy of PACT for patients with CLBP. TRIAL REGISTRATION NUMBER: ISRCTN95392287; Pre-results. PMID- 27267110 TI - Research priorities relating to the debate on assisted dying: what do we still need to know? Results of a modified Delphi technique. AB - OBJECTIVE: To identify the main areas of uncertainty and subsequent research priorities to inform the ongoing debate around assisted dying. DESIGN: Two-round electronic modified Delphi consultation with experts and interested bodies. SETTING AND PARTICIPANTS: 110 groups and individuals interested in the subject of end-of-life care and/or assisted dying were approached to participate. Respondents included health and social care professionals, researchers, campaigners, patients and carers predominantly based in the UK. In the first round, the respondents were asked to propose high-priority research questions related to the topic of assisted dying. The collected research questions were then deduplicated and presented to all respondents in a second round in which they could rate each question in terms of importance. RESULTS: 24% and 26% of participants responded to the first and second rounds, respectively. Respondents suggested 85 unique research questions in the first round. These were grouped by theme and rated in terms of importance in the second round. Emergent themes were as follows: palliative care/symptom control; patient characteristics, experiences and decisions; families and carers; society and the general public; arguments for and against assisted dying; international experiences/analysis of existing national data; suicide; mental health, psychological and psychosocial considerations; comorbidities; the role of clinicians; environment and external influences; broader topics incorporating assisted dying; and moral, ethical and legal issues. 10 of the 85 proposed questions were rated as being important (>=7/10) by at least 50% of respondents. CONCLUSIONS: Research questions with the highest levels of consensus were predominantly concerned with understanding how and why people make end-of-life decisions, and which factors influence those decisions. Dissemination of these findings alongside a focused examination of the existing literature may be the most effective way to add evidence to the ongoing debate around assisted dying. PMID- 27267111 TI - beta-Blockers for the prevention of acute exacerbations of chronic obstructive pulmonary disease (betaLOCK COPD): a randomised controlled study protocol. AB - INTRODUCTION: A substantial majority of chronic obstructive pulmonary disease (COPD)-related morbidity, mortality and healthcare costs are due to acute exacerbations, but existing medications have only a modest effect on reducing their frequency, even when used in combination. Observational studies suggest beta-blockers may reduce the risk of COPD exacerbations; thus, we will conduct a randomised, placebo-controlled trial to definitively assess the impact of metoprolol succinate on the rate of COPD exacerbations. METHODS AND ANALYSES: This is a multicentre, placebo-controlled, double-blind, prospective randomised trial that will enrol 1028 patients with at least moderately severe COPD over a 3 year period. Participants with at least moderate COPD will be randomised in a 1:1 fashion to receive metoprolol or placebo; the cohort will be enriched for patients at high risk for exacerbations. Patients will be screened and then randomised over a 2-week period and will then undergo a dose titration period for the following 6 weeks. Thereafter, patients will be followed for 42 additional weeks on their target dose of metoprolol or placebo followed by a 4-week washout period. The primary end point is time to first occurrence of an acute exacerbation during the treatment period. Secondary end points include rates and severity of COPD exacerbations; rate of major cardiovascular events; all-cause mortality; lung function (forced expiratory volume in 1 s (FEV1)); dyspnoea; quality of life; exercise capacity; markers of cardiac stretch (pro-NT brain natriuretic peptide) and systemic inflammation (high-sensitivity C reactive protein and fibrinogen). Analyses will be performed on an intent-to-treat basis. ETHICS AND DISSEMINATION: The study protocol has been approved by the Department of Defense Human Protection Research Office and will be approved by the institutional review board of all participating centres. Study findings will be disseminated through presentations at national and international conferences and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02587351; Pre-results. PMID- 27267112 TI - The prevalence and genotypic analysis of Toxoplasma gondii from individuals in Scotland, 2006-2012. AB - BACKGROUND: Contemporary information relating to the prevalence of Toxoplasma gondii in humans is lacking for the UK population, with even less information available about the human prevalence of the parasite in Scotland. To address this, two different study groups were used to determine the prevalence and genotypes of Toxoplasma gondii in the Scottish population. METHODS: The first study group included serum samples from blood donors (n = 3273) over a four-year period (2006-2009) and the second study group comprised of DNA samples extracted from human brains (n = 151) over a five-year period (2008-2012). A T. gondii IgG ELISA was performed to determine seroprevalence and available sera from individuals who had seroconverted were tested by TgERP ELISA (sporozoite specific antigen). Human brain DNA was tested for T. gondii by ITS1 PCR and positives genotyped at the SAG3 and GRA6 loci by PCR-RFLP analysis. RESULTS: Seroprevalence to T. gondii from blood donors was found to be 13.2 % (95 % CI: 11.5-15.1 %). Evidence of seroconversion (n = 2) as well as reversion to sero-negative status (n = 6) was evident from blood donors who had donated within all four collection periods (n = 184). The TgERP ELISA (indicating oocyst infection) was positive for one individual. The molecular detection of T. gondii DNA from human brains indicated a prevalence of 17.9 % (95 % CI: 12.1-24.9 %), with genotyping identifying alleles for types I and III. An increase in age was associated with an increase in detection of the parasite within both study groups. CONCLUSIONS: Our research provides current figures for the prevalence of T. gondii in Scotland and also shows evidence of seroreversion within the cohort of blood donors. In both study groups there was a correlation between increasing age and an increase in T. gondii prevalence, indicating that acquired infection plays an important role within the Scottish population. PMID- 27267113 TI - Transition to blended learning: experiences from the first year of our blended learning Bachelor of Nursing Studies programme. AB - BACKGROUND: The School of Nursing at Dublin City University offered a new blended learning Bachelor of Nursing Studies programme in the academic year 2011. AIM: To document the experiences of the academic team making the transition from a face to-face classroom-delivered programme to the new blended learning format. METHOD: Academics who delivered the programme were asked to describe their experiences of developing the new programme via two focus groups. RESULTS: Five dominant themes were identified: Staff Readiness; Student Readiness; Programme Delivery and Student Engagement; Assessment of Module Learning Outcomes and Feedback; and Reflecting on the First Year and Thinking of the Future. Face-to-face tutorials were identified as very important to both academics and students. Reservations about whether migrating the programme to an online format encouraged students to engage in additional practices of plagiarism were expressed by some. Student ability/readiness to engage with technology-enhanced learning was an important determinant of their own success academically. DISCUSSION: In the field of nursing blended learning is a relatively new and emerging field which will require huge cultural shifts for staff and students alike. PMID- 27267114 TI - Effects of sediment amended with Deepwater Horizon incident slick oil on the infaunal amphipod Leptocheirus plumulosus. AB - Crude oil released from the Deepwater Horizon disaster into the Gulf of Mexico posed potential impacts to infaunal invertebrates inhabiting near shore habitats. The effects of sediment-associated weathered slick oil on the amphipod Leptocheirus plumulosus was assessed using 28-d exposures to total PAH sediment concentrations ranging from 0.3 to 24mg/kg (sum of 50 PAHs or tPAH50). Survival and growth rate were significantly decreased in the 2.6, 11.4 and 24.2mg/kg treatments, but only growth in 5.5mg/kg. Offspring production was dramatically decreased but was variable and significantly different only for 24.2mg/kg. The concentrations associated with 20% decreases relative to reference were 1.05 (95% CI=0-2.89) mg/kg tPAH50 for growth rate and 0.632 (95% CI=0.11-2.15) mg/kg tPAH50 for offspring production. The concentrations of PAHs affecting amphipods are within the range of concentrations measured in marsh areas reportedly impacted by DWH oil after its release. PMID- 27267115 TI - Effects of hypoxia caused by mussel farming on benthic foraminifera in semi closed Gamak Bay, South Korea. AB - Seawater monitoring and geochemical and benthic foraminiferal analysis of sediments were conducted to identify the effects of hypoxia created by a mussel farm on benthic foraminifera in a semi-closed bay. Extremely polluted reductive conditions with a high content of organic matter (OM) at >12.0% and oxygen minimum zones (OMZs) with dissolved oxygen (DO) <0.4mg?L(-1) were formed below the mussel farm in the northwest area of Gamak Bay, and gradually diffused toward the south. Highly similar patterns of variation were observed in species diversity, abundance frequency, and benthic foraminiferal assemblage distributed from Elphidium subarcticum-Ammonia beccarii in the northwest area through E. subarcticum-A. beccarii-Trochammina hadai, E. subarcticum-A. beccarii Elphidiumclavatum, and E. clavatum-Ammonia ketienziensis in the southern area. These phenomena were caused by hydrodynamics in the current water mass. It was thought that E. subarcticum is a bioindicator of organic pollution caused by the mussel farm. PMID- 27267116 TI - Spatial distribution and pollution evaluation of heavy metals in Yangtze estuary sediment. AB - To analyze the spatial distribution patterns and ecological risks of heavy metals, 30 sediment samples were taken in the Yangtze River Estuary (YRE) in May 2011. The content of Al, As, Cr, Cu, Fe, Mn, Ni and Pb increased as follows: inner-region5 decades. Long term TCS monotherapy has been associated with adverse cutaneous effects including atrophy, rebound flares, and increased percutaneous absorption with potential for adverse systemic effects. Topical calcineurin inhibitors (TCIs), tacrolimus and pimecrolimus, available for 1-2 decades, are not associated with atrophy or increased percutaneous absorption after prolonged use and have much lower potential for systemic effects. However, since 2006 TCIs have carried a controversial Boxed Warning based on a theoretical risk of malignancy (eg, skin and lymphoma) that has limited TCI use for standard-of-care maintenance therapy. METHODS: A comparative systematic search of PubMed was done for long-term (>=12 week) clinical trials of TCS or TCI treatment in patients <12 years with AD. Citations were reviewed for inclusion based on MeSH terms, abstracts, and relevant article text. Studies were excluded if they did not encompass subjects <12 years, or were <12 weeks' duration, retrospective, meta-analyses, or limited to anecdotal case reports. RESULTS: Of 27 trials meeting criteria, 21 included 5825 pediatric patients treated with TCIs, and 6 included 1999 patients treated with TCS. TCS studies were limited to low- to mid-potency products, and all but one study lacked a vehicle control. Eight TCI studies were vehicle-controlled, and safety data were well reported, with <=5 % of patients reporting discontinuation due to adverse effects (DAEs). Cutaneous and systemic adverse events (AEs) were similar in TCI and vehicle groups, with no reports of lymphoma. Safety data in TCS trials were less well reported. DAE incidence was addressed in just 2 trials, and systemic and cutaneous AEs were mostly unreported. CONCLUSIONS: Data supporting long-term use of TCIs are robust, documenting safety and efficacy, while data supporting long-term TCS use are limited to low- to mid potency products. Our review identifies a lack of information on the safety of commonly prescribed, long-term monotherapy with mid- to high-potency TCS in pediatric AD, and supports standard-of-care maintenance therapy with TCIs and intermittent use of low- to mid-potency TCS for flares. PMID- 27267136 TI - Effect of Mutation and Substrate Binding on the Stability of Cytochrome P450BM3 Variants. AB - Cytochrome P450BM3 is a heme-containing enzyme from Bacillus megaterium that exhibits high monooxygenase activity and has a self-sufficient electron transfer system in the full-length enzyme. Its potential synthetic applications drive protein engineering efforts to produce variants capable of oxidizing nonnative substrates such as pharmaceuticals and aromatic pollutants. However, promiscuous P450BM3 mutants often exhibit lower stability, thereby hindering their industrial application. This study demonstrated that the heme domain R47L/F87V/L188Q/E267V/F81I pentuple mutant (PM) is destabilized because of the disruption of hydrophobic contacts and salt bridge interactions. This was directly observed from crystal structures of PM in the presence and absence of ligands (palmitic acid and metyrapone). The instability of the tertiary structure and heme environment of substrate-free PM was confirmed by pulse proteolysis and circular dichroism, respectively. Binding of the inhibitor, metyrapone, significantly stabilized PM, but the presence of the native substrate, palmitic acid, had no effect. On the basis of high-temperature molecular dynamics simulations, the lid domain, beta-sheet 1, and Cys ligand loop (a beta-bulge segment connected to the heme) are the most labile regions and, thus, potential sites for stabilizing mutations. Possible approaches to stabilization include improvement of hydrophobic packing interactions in the lid domain and introduction of new salt bridges into beta-sheet 1 and the heme region. An understanding of the molecular factors behind the loss of stability of P450BM3 variants therefore expedites site-directed mutagenesis studies aimed at developing thermostability. PMID- 27267137 TI - Multispectral Chiral Imaging with a Metalens. AB - The vast majority of biologically active compounds, ranging from amino acids to essential nutrients such as glucose, possess intrinsic handedness. This in turn gives rise to chiral optical properties that provide a basis for detecting and quantifying enantio-specific concentrations of these molecules. However, traditional chiroptical spectroscopy and imaging techniques require cascading of multiple optical components in sophisticated setups. Here, we present a planar lens with an engineered dispersive response, which simultaneously forms two images with opposite helicity of an object within the same field-of-view. In this way, chiroptical properties can be probed across the visible spectrum using only the lens and a camera without the addition of polarizers or dispersive optical devices. We map the circular dichroism of the exoskeleton of a chiral beetle, Chrysina gloriosa, which is known to exhibit high reflectivity of left-circularly polarized light, with high spatial resolution limited by the numerical aperture of the planar lens. Our results demonstrate the potential of metasurfaces in realizing a compact and multifunctional device with unprecedented imaging capabilities. PMID- 27267138 TI - Undergraduate Training in Human Sexuality-Evaluation of the Impact on Medical Doctors' Practice Ten Years After Graduation. AB - INTRODUCTION: It has been suggested that an indicator of a doctor's ability to assess patients' sexual function relates to the level of earlier training. The amount and quality of training the doctor receives at the undergraduate level and beyond could contribute to the doctor's confidence and competence. AIMS: To evaluate whether doctors found that the teaching in human sexuality received at medical school was sufficient for their future practice and whether their chosen medical specialty and exposure to issues related to sexual health affected this opinion. METHODS: One hundred seventy doctors maintaining contact with the University of Sheffield Medical School Alumni Office after qualifying in 2004 were sent self-completion postal questionnaires. Space was allocated for supplementary comments to their answers. MAIN OUTCOME MEASURES: Self-completion postal questionnaire. RESULTS: Although the response rate was low, there appeared to be an impact of the teaching of human sexuality on the clinical practice of doctors. More than two-thirds of respondents rated the teaching as useful and more than 70% felt more confident in diagnosing and managing male and female sexual issues. CONCLUSION: The results show a link between the undergraduate teaching of sexual medicine and education and a subsequent proactive approach to sexuality issues; unfortunately, the study does not provide any information about the level of skills or ability in this field of medicine. We have confirmed that the Sheffield model might be suitable for teaching sexual medicine issues in the United Kingdom but cannot confirm that the current format is suitable for international undergraduate audiences. Future study could include other medical schools and a comparison of sexual medicine practice among physicians who received undergraduate medical education and overall numbers could be increased to compare current practice with the number of hours of sexual medicine education as a key parameter. PMID- 27267139 TI - Use of a Self-Reflection Tool to Enhance Resident Learning on an Adolescent Medicine Rotation. AB - PURPOSE: Adolescent Medicine (AM) educators in pediatric residency programs are seeking new ways to engage learners in adolescent health. This mixed-methods study presents a novel self-reflection tool and addresses whether self-reflection enhanced residents' perception of the value of an adolescent rotation, in particular, its relevance to their future practice. METHODS: The self-reflection tool included 17 Likert scale items on residents' comfort with the essential tasks of adolescent care and open-ended questions that promoted self-reflection and goal setting. Semi-structured, postrotation interviews encouraged residents to discuss their experiences. Likert scale data were analyzed using descriptive statistics, and interview notes and written comments on the self-reflection tool were combined for qualitative data analysis. RESULTS: Residents' pre-to post-self evaluations showed statistically significant increases in comfort with most of the adolescent health care tasks. Four major themes emerged from our qualitative analysis: (1) the value of observing skilled attendings as role models; (2) the comfort gained through broad and frequent adolescent care experiences; (3) the career relevance of AM; and (4) the ability to set personally meaningful goals for the rotation. CONCLUSIONS: Residents used the self-reflection tool to mindfully set goals and found their AM education valuable and relevant to their future careers. Our tool helped make explicit to residents the norms, values, and beliefs of the hidden curriculum applied to the care of adolescents and helped them to improve the self-assessed quality of their rapport and communications with adolescents. We conclude that a structured self-reflection exercise can enhance residents' experiences on an AM rotation. PMID- 27267140 TI - Pathological Internet Use Is on the Rise Among European Adolescents. AB - PURPOSE: Increased Internet accessibility has been accompanied by an increased awareness of pathological Internet use (PIU). The aim of the study was to investigate a potential increase of PIU among European adolescents. METHODS: Comparable data from two large cross-sectional multicentre, school-based studies conducted in 2009/2010 and 2011/2012 in five European countries (Estonia, Germany, Italy, Romania, and Spain) were used. The Young's Diagnostic Questionnaire was used to assess the prevalence of PIU. RESULTS: The comparison of the two samples provides evidence that the prevalence of PIU is on the rise (4.01%-6.87%, odds ratio = 1.69, p < .001) except in Germany. Comparison with data on Internet accessibility suggests that the rise in prevalence of adolescent PIU may be a consequence of increased Internet accessibility. CONCLUSIONS: Our findings are the first data to confirm the rise of PIU among European adolescents. They definitively warrant further efforts in the implementation and evaluation of preventive interventions. PMID- 27267141 TI - A Depression Prevention Intervention for Adolescents in the Emergency Department. AB - PURPOSE: To evaluate acceptability and feasibility of a theoretically based two part (brief in-person + 8-week automated text message) depression prevention program, "intervention for DepressiOn and Violence prevention in the Emergency department" (iDOVE), for high-risk adolescents. METHODS: English-speaking emergency department (ED) patients (age 13-17, any chief complaint) were sequentially approached for consent on a convenience sample of shifts and screened for inclusion based on current depressive symptoms and past-year violence. After consent, baseline assessments were obtained; all participants were enrolled in the two-part intervention (brief in-ED + 8-week two-way text messaging). At 8 weeks, quantitative and qualitative follow-up assessments were obtained. Measures included feasibility, acceptability, and preliminary data on efficacy. Qualitative data were transcribed verbatim, double coded, and interpreted using thematic analysis. Quantitative results were analyzed descriptively and with paired t tests. RESULTS: As planned, 16 participants (eight each gender) were recruited (75% of those who were eligible; 66% nonwhite, 63% low income, mean age 15.4). The intervention had high feasibility and acceptability: 93.8% completed 8-week follow-up; 80% of daily text messages received responses; 31% of participants requested >=1 "on-demand" text message. In-person and text message portions were rated as good/excellent by 87%. Qualitatively, participants articulated: (1) iDOVE was welcome and helpful, if unexpected in the ED; (2) the daily text message mood assessment was "most important"; (3) content was "uplifting"; and (4) balancing intervention "relatability" and automation was challenging. Participants' mean DeltaBDI-2 (Beck Depression Inventory) from baseline to 8-week follow-up was -4.9, (p = .02). CONCLUSIONS: This automated preventive text message intervention is acceptable and feasible. Qualitative data emphasize the importance of creating positive, relevant, and interactive digital health tools for adolescents. PMID- 27267143 TI - Diffuse-type tenosynovial giant cell tumour: Current treatment concepts and future perspectives. AB - At present, the optimal treatment strategy in patients with diffuse-type tenosynovial giant cell tumour (D-TGCT) is unclear. The purpose of this review was to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of D-TGCT as well as related therapeutic implications. Epidemiology, clinical features, and the pathogenesis of D-TGCT and the most widely used treatment modalities are described. D-TGCT is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic and require multiple surgical procedures during their lifetime. Currently, surgery is the main treatment for patients with D-TGCT, with relapse rates ranging from 14% to 55%. Radiosynovectomy and external beam radiotherapy have been used in combination with surgical excision or as single modalities. The finding that D-TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumour, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as imatinib, nilotinib, PLX3397, and the monoclonal antibody RG7155. In conclusion, D-TGCT impairs patients' quality of life significantly. The evidence that the pathogenetic loop of D-TGCT can be inhibited could potentially change the therapeutic armamentarium for this condition. Clinical trials of agents that target D-TGCT are currently ongoing. In the meantime, international registries should be activated in order to provide useful information on this relatively rare tumour. PMID- 27267142 TI - Social Epidemiology of Depression and Anxiety by Gender Identity. AB - PURPOSE: This study investigates depression and anxiety in gender minority (i.e., transgender and/or gender nonconforming) compared with nongender minority (cisgender) young adults. METHODS: Data were from the Growing Up Today Study, a national cohort of U.S. young adults. A two-step method (maternal-reported natal sex in 1996 cross-classified with participant-reported current gender identity in 2010) was used to identify gender minority and nongender minority respondents (n = 7,831; mean age = 26 years). Differences in past week depressive symptoms and anxious symptoms were examined cross-sectionally by gender identity. Gender minority and nongender minority respondents were compared using age-adjusted logistic regression models. RESULTS: In gender minorities, the prevalence of depressive and anxious symptoms meeting clinical cutoffs was 52% and 38%, respectively, compared with nongender minorities (27% and 30% in females and 25% and 14% in males; p < .01). CONCLUSIONS: Gender identity is an understudied social determinant of mental health. Surveillance efforts to monitor mental health disparities should include survey questions to assess gender identity in epidemiologic research. Research and interventions to understand and ameliorate mental health disparities by gender identity are needed. PMID- 27267144 TI - European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results of the treatment of skin cancer. AB - Electrochemotherapy is an effective and safe method for local treatment of cutaneous and subcutaneous tumours, where electric pulses cause increased permeability of cell membranes in the tumour mass, enabling dramatically enhanced effectiveness of bleomycin and other hydrophilic drugs. Here, we report results of a European multi-institutional prospective study of the effectiveness of electrochemotherapy in the treatment of skin cancer of the head and neck (HN) area, where standard treatments had either failed or were not deemed suitable or declined by the patient. A total of 105 patients affected by primary or recurrent skin cancer of the HN area were enrolled; of these, 99 were eligible for evaluation of tumour response. By far, the majority (82%) were treated only once, and 18% of patients had a second treatment. The objective response was highest for basal cell carcinoma (97%) and for other histologies was 74%. Small, primary, and treatment-naive carcinomas responded significantly better (p < 0.05), as investigated by univariate analysis. Electrochemotherapy was well tolerated and led to a significant improvement of quality of life, estimated by the European Organisation for Research and Treatment of Cancer quality of life questionnaires. At 1-year follow-up, the percentages of overall and disease-free survival were 76% and 89%, respectively. Electrochemotherapy is an effective option for skin cancers of the HN area and can be considered a feasible alternative to standard treatments when such an alternative is appropriate. The precise role for electrochemotherapy in the treatment algorithm for non-melanoma skin cancer of the HN region requires data from future randomised controlled studies. (ISRCTN registry N. 30427). PMID- 27267146 TI - Vertebral shape and body elongation in Triturus newts. AB - Body elongation in vertebrates is often related to a lengthening of the vertebrae and an increase in their number. Changes in the number and shape of vertebrae are not necessarily linked. In tailed amphibians, a change in body shape is mostly associated with an increase in the number of trunk and tail vertebrae. Body elongation without a numerical change of vertebrae is rare. In Triturus aquatic salamanders body elongation is achieved by trunk elongation through an increase in the number of trunk vertebrae. We used computed microtomography and three dimensional geometric morphometrics to document the size, shape and number of trunk vertebrae in seven Triturus species. The data suggest that body elongation has occurred more frequently than body shortening, possibly related to a more aquatic versus a more terrestrial locomotor style. Our results show that body elongation is achieved through an increase in the number of trunk vertebrae, and that interspecific differences in vertebral shape are correlated with this pattern of elongation. More gracile trunk vertebrae were found in the more elongated species. The shape differences are such that single trunk vertebrae can be used for the identification of species with a possible application in the identification of subfossil and fossil material. PMID- 27267145 TI - Towards low carbon society in Iskandar Malaysia: Implementation and feasibility of community organic waste composting. AB - Rapid population growth and urbanisation have generated large amount of municipal solid waste (MSW) in many cities. Up to 40-60% of Malaysia's MSW is reported to be food waste where such waste is highly putrescible and can cause bad odour and public health issue if its disposal is delayed. In this study, the implementation of community composting in a village within Iskandar Malaysia is presented as a case study to showcase effective MSW management and mitigation of GHG emission. The selected village, Felda Taib Andak (FTA), is located within a palm oil plantation and a crude palm oil processing mill. This project showcases a community-composting prototype to compost food and oil palm wastes into high quality compost. The objective of this article is to highlight the economic and environment impacts of a community-based composting project to the key stakeholders in the community, including residents, oil palm plantation owners and palm oil mill operators by comparing three different scenarios, through a life cycle approach, in terms of the greenhouse gas emission and cost benefit analysis. First scenario is the baseline case, where all the domestic waste is sent to landfill site. In the second scenario, a small-scale centralised composting project was implemented. In the third scenario, the data obtained from Scenario 2 was used to do a projection on the GHG emission and costing analysis for a pilot-scale centralised composting plant. The study showed a reduction potential of 71.64% on GHG emission through the diversion of food waste from landfill, compost utilisation and significant revenue from the compost sale in Scenario 3. This thus provided better insight into the feasibility and desirability in implementing a pilot-scale centralised composting plant for a sub urban community in Malaysia to achieve a low carbon and self-sustainable society, in terms of environment and economic aspects. PMID- 27267147 TI - Locomotor flexibility of Polypterus senegalus across various aquatic and terrestrial substrates. AB - Amphibious fishes show wide variation in form and function. Examination of terrestrial locomotion in fishes has largely focused on highly specialized taxa. From an evolutionary perspective we are interested in how relatively unspecialized fishes locomote when exposed to different terrestrial environments. In this study, we explore the locomotory repertoire of the basal actinopterygian Polypterus senegalus. We describe its terrestrial locomotory strategies on different surfaces and compare them with steady aquatic locomotion. Our study is the first to describe axial and appendicular-based terrestrial locomotion across a range of substrates in this species and shows two distinct terrestrial gaits in P. senegalus, each with substantial variation. One uses body undulation against complex surfaces and the other incorporates alternating, supportive pectoral fins to achieve a tetrapod-like gait. Gait use is correlated with substrate. P. senegalus uses body and pectoral fins in diverse ways, showing opportunistic and flexible strategies of navigating novel environments. PMID- 27267148 TI - The economic burden of tuberous sclerosis complex in the UK: A retrospective cohort study in the Clinical Practice Research Datalink. AB - BACKGROUND: Tuberous sclerosis complex (TSC) is a multi-system genetic disorder characterized by the development of diverse clinical manifestations. The complexity of this disease is likely to result in substantial challenges and costs in disease management throughout the patient's lifetime. This retrospective database study aims to quantify healthcare resources utilized by TSC patients. METHODS: TSC patients in the Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database were identified between January 1987 and June 2013. Analyses were conducted over the most recent 3-year period of data and stratified by pediatric (< 18) and adult patients. Prescriptions, procedures, diagnostic tests, and healthcare encounters were reported in comparison with a matched comparator cohort. Costs and key economic drivers by primary organ system manifestations were also examined. RESULTS: A total of 286 patients with TSC were identified and consistently reported 2-fold greater resource use than the matched presumably healthy controls. Despite this comparatively greater resource use, half of TSC patients did not record any procedures, and 20% of patients did not record any diagnostic tests; however, inpatient hospitalizations were greater for the TSC cohort (3.1 vs 1.3), but length of stay was comparable. TSC patients had costs totaling L12,681 per patient over the 3-year period, a figure 2.7-fold greater than the total costs in the comparator cohort (L4,777). Costs for patients with specific primary manifestations were even greater, with brain manifestations incurring L22,139 per affected patient. Kidney and nervous system manifestations were the main cost drivers. CONCLUSIONS: The economic burden of TSC and its impact on NHS healthcare resources is mostly attributable to the broad spectrum of manifestations that develop within multiple organ systems. TSC patients may benefit from co-ordinated care based on their requirement for high numbers of healthcare visits across specialties. PMID- 27267149 TI - Frontier Orbital Engineering of Metal-Organic Frameworks with Extended Inorganic Connectivity: Porous Alkaline-Earth Oxides. AB - The development of conductive metal-organic frameworks is challenging owing to poor electronic communication between metal clusters and the organic ligands that bridge them. One route to overcoming this bottleneck is to extend the inorganic dimensionality, while using the organic components to provide chemical functionality. Using density functional theory methods, we demonstrate how the properties of the alkaline-earth oxides SrO and BaO are transformed upon formation of porous solids with organic oxygen sources (acetate and trifluoroacetate). The electron affinity is significantly enhanced in the hybrid materials, while the ionization potential can be tuned over a large range with the polarity of the organic moiety. Furthermore, because of their high-vacuum fraction, these materials have dielectric properties suitable for low-kappa applications. PMID- 27267150 TI - Synthesis, High-Resolution Infrared Spectroscopy, and Vibrational Structure of Cubane, C8H8. AB - Carbon-cage molecules have generated a considerable interest from both experimental and theoretical points of view. We recently performed a high resolution study of adamantane (C10H16), the smallest hydrocarbon cage belonging to the diamandoid family ( Pirali , O. ; et al. J. Chem. Phys. 2012 , 136 , 024310 ). There exist another family of hydrocarbon cages with additional interesting chemical properties: the so-called platonic hydrocarbons that comprise dodecahedrane (C20H20) and cubane (C8H8). Both possess C-C bond angles that deviate from the tetrahedral angle (109.8 degrees ) of the sp(3) hybridized form of carbon. This generates a considerable strain in the molecule. We report a new wide-range high-resolution study of the infrared spectrum of cubane. The sample was synthesized in Bari upon decarboxylation of 1,4-cubanedicarboxylic acid thanks to the improved synthesis of literature. Several spectra have been recorded at the AILES beamline of the SOLEIL synchrotron facility. They cover the 600-3200 cm(-1) region. Besides the three infrared-active fundamentals (nu10, nu11, and nu12), we could record many combination bands, all of them displaying a well-resolved octahedral rotational structure. We present here a preliminary analysis of some of the recorded bands, performed thanks the SPVIEW and XTDS software, based on the tensorial formalism developed in the Dijon group. A comparison with ab initio calculations, allowing to identify some combination bands, is also presented. PMID- 27267151 TI - Mindfulness Meditation-Based Intervention Is Feasible, Acceptable, and Safe for Chronic Low Back Pain Requiring Long-Term Daily Opioid Therapy. AB - OBJECTIVE: Although mindfulness meditation (MM) is increasingly used for chronic pain treatment, limited evidence supports its clinical application for opioid treated chronic low back pain (CLBP). The goal of this study was to determine feasibility, acceptability, and safety of an MM-based intervention in patients with CLBP requiring daily opioid therapy. DESIGN: 26-week pilot randomized controlled trial comparing MM-based intervention, combined with usual care, to usual care alone. SETTING: Outpatient. PATIENTS: Adults with CLBP treated with >=30 mg of morphine-equivalent dose (MED) per day for 3 months or longer. INTERVENTIONS: Targeted MM-based intervention consisted of eight weekly 2-hour group sessions and home practice (30 minutes/d, 6 days/wk) during the study. "Usual care" for opioid-treated CLBP was provided to participants by their regular clinicians. OUTCOME MEASURES: Feasibility and acceptability of the MM intervention were assessed by adherence to intervention protocol and treatment satisfaction among experimental participants. Safety was evaluated by inquiry about side effects/adverse events and opioid dose among all study participants. RESULTS: Thirty-five participants enrolled during the 10-week recruitment period. The mean age (+/-standard deviation) was 51.8 +/- 9.7 years; the patients were predominantly female, with substantial CLBP-related pain and disability, and treated with 148.3 +/- 129.2 mg of MED per day. All participants completed baseline assessments; none missed both follow-up assessments or withdrew. Among experimental participants (n = 21), 19 attended 1 or more intervention sessions and 14 attended 4 or more. They reported, on average, 164.0 +/- 122.1 minutes of formal practice per week during the 26-week study and 103.5 +/- 111.5 minutes of brief, informal practice per week. Seventeen patients evaluated the intervention, indicating satisfaction; their qualitative responses described the course as useful for pain management (n = 10) and for improving pain coping skills (n = 8). No serious adverse events or safety concerns occurred among the study participants. CONCLUSIONS: MM-based intervention is feasible, acceptable, and safe in opioid-treated CLBP. PMID- 27267152 TI - Population genetic structure of the freshwater snail, Bulinus globosus, (Gastropoda: Planorbidae) from selected habitats of KwaZulu-Natal, South Africa. AB - The freshwater snail Bulinus globosus is an important intermediate host of Schistosoma haematobium, the causative agent of urinary schistosomiasis. This disease is of major health concern, especially in Africa where the majority of cases have been reported. In this study the inter- and intra-genetic diversity and population genetic structure of B. globosus from nine locations in the KwaZulu-Natal province of South Africa was studied using four polymorphic microsatellite loci (BgZ1-BgZ4). Moderate genetic diversity was detected within populations with a mean diversity (HE) of 0.49+/-0.09. The majority of populations significantly deviated from Hardy-Weinberg equilibrium (p<0.05), due to a deficit of heterozygotes. Such deviations may be due to founder events that were caused by bottlenecks that occurred as a result of frequent droughts and flooding that these snails' habitats are exposed to. Overall, the populations studied seem to be partially inbreeders/selfers with mean estimates of 0.24/0.38. A discernable genetic structure was elucidated among populations as evident by the mean pairwise FST of 0.58+/-0.13. There was no significant association between genetic and geographical distance among populations, an indication of limited gene flow. This increases the chances of populations losing alleles due to genetic drift. Populations in close proximity demonstrated high genetic differentiation (58.77% total variation) due to allelic differences between them. The sample populations fell into 12 clusters, however, the populations from uMkhanyakude and uThungulu exhibited no discernable genetic structure. Genetically, the Bhobhoyi site found within the uGu district was equidistant to the two main sampling regions. PMID- 27267153 TI - Understanding Ion Binding Affinity and Selectivity in beta-Parvalbumin Using Molecular Dynamics and Mean Spherical Approximation Theory. AB - Parvalbumin (PV) is a globular calcium (Ca(2+))-selective protein expressed in a variety of biological tissues. Our computational studies of the rat beta parvalbumin (beta-PV) isoform seek to elucidate the molecular thermodynamics of Ca(2+) versus magnesium (Mg(2+)) binding at the protein's two EF-hand motifs. Specifically, we have utilized molecular dynamics (MD) simulations and a mean field electrolyte model (mean spherical approximation (MSA) theory) to delineate how the EF-hand scaffold controls the "local" thermodynamics of Ca(2+) binding selectivity over Mg(2+). Our MD simulations provide the probability density of metal-chelating oxygens within the EF-hand scaffolds for both Ca(2+) and Mg(2+), as well the conformational strain induced by Mg(2+) relative to Ca(2+) binding. MSA theory utilizes the binding domain oxygen and charge distributions to predict the chemical potential of ion binding, as well as their corresponding concentrations within the binding domain. We find that the electrostatic and steric contributions toward ion binding were similar for Mg(2+) and Ca(2+), yet the latter was 5.5 kcal/mol lower in enthalpy when internal strain within the EF hand was considered. We therefore speculate that beyond differences in dehydration energies for the Ca(2+) versus Mg(2+), strain induced in the beta-PV EF hand by cation binding significantly contributes to the nearly 10,000-fold difference in binding affinity reported in the literature. We further complemented our analyses of local factors governing cation binding selectivity with whole-protein (global) contributions, such as interhelical residue-residue contacts and solvent exposure of hydrophobic surface. These contributions were found to be comparable for both Ca(2+)- and Mg(2+)-bound beta-PV, which may implicate local factors, EF-hand strain, and dehydration, in providing the primary means of selectivity. We anticipate these methods could be used to estimate metal binding thermodynamics across a broad range of PV sequence homologues and EF-hand-containing, Ca(2+) binding proteins. PMID- 27267155 TI - Applying multivariate statistics to discriminate uranium ore concentrate geolocations using (radio)chemical data in support of nuclear forensic investigations. AB - The application of Principal Components Analysis (PCA) to U and Th series gamma spectrometry data provides a discriminatory tool to help determine the provenance of illicitly recovered uranium ore concentrates (UOCs). The PCA is applied to a database of radiometric signatures from 19 historic UOCs from Australia, Canada, and the USA representing many uranium geological deposits. In this study a key process to obtain accurate radiometric data (gamma and alpha) is to digest the U ores and UOCs using a lithium tetraborate fusion. Six UOCs from the same sample set were analysed 'blind' and compared against the database to identify their geolocation. These UOCs were all accurately linked to their correct geolocations which can aid the forensic laboratory in determining which further analytical techniques should be used to improve the confidence of the particular location. PMID- 27267156 TI - Extraction, purification and anti-radiation activity of persimmon tannin from Diospyros kaki L.f. AB - In this study, persimmon tannin was extracted from Diospyros kaki L.f. using ultrasound-assisted extraction and purified by D101 macroporous resin column chromatography and polysulfone ultrafiltration membrane. The tannin content of the final persimmon tannin extracts was attained to 39.56% calculated as catechin equivalents. Also, the radioprotective effects of persimmon tannin for HEK 293T cells proliferation and apoptosis after Gamma irradiation were investigated by CCK-8, Hoechst 33258 staining, flow cytometry assay and intracellular reactive oxygen species assay (ROS). Persimmon tannin was pre-incubated with HEK 293T cells for 12 h prior to Gamma irradiation. It was found that pretreatment with persimmon tannin increased cell viability and inhibited generation of Gamma radiation induced ROS in HEK 293T cells exposed to 8 Gy Gamma-radiation. The percentage of apoptotic cells were only 6.7% when the radiation dose was 8 Gy and pretreated with 200 MUg/ml of persimmon tannin. All these results indicated that persimmon tannin offered a potent radioprotective effect on cell vitality and cell apoptosis of Gamma-radiation exposure in HEK 293T cells. This study would serve as a pre-clinical evaluation of persimmon tannin for use in people with radiation protection. PMID- 27267157 TI - Impacts of C-uptake by plants on the spatial distribution of 14C accumulated in vegetation around a nuclear facility-Application of a sophisticated land surface 14C model to the Rokkasho reprocessing plant, Japan. AB - The impacts of carbon uptake by plants on the spatial distribution of radiocarbon (14C) accumulated in vegetation around a nuclear facility were investigated by numerical simulations using a sophisticated land surface 14C model (SOLVEG-II). In the simulation, SOLVEG-II was combined with a mesoscale meteorological model and an atmospheric dispersion model. The model combination was applied to simulate the transfer of 14CO2 and to assess the radiological impact of 14C accumulation in rice grains during test operations of the Rokkasho reprocessing plant (RRP), Japan, in 2007. The calculated 14C-specific activities in rice grains agreed with the observed activities in paddy fields around the RRP within a factor of four. The annual effective dose delivered from 14C in the rice grain was estimated to be less than 0.7 MUSv, only 0.07% of the annual effective dose limit of 1 mSv for the public. Numerical experiments of hypothetical continuous atmospheric 14CO2 release from the RRP showed that the 14C-specific activities of rice plants at harvest differed from the annual mean activities in the air. The difference was attributed to seasonal variations in the atmospheric 14CO2 concentration and the growth of the rice plant. Accumulation of 14C in the rice plant significantly increased when 14CO2 releases were limited during daytime hours, compared with the results observed during the nighttime. These results indicated that plant growth stages and diurnal photosynthesis should be considered in predictions of the ingestion dose of 14C for long-term chronic releases and short-term diurnal releases of 14CO2, respectively. PMID- 27267154 TI - A randomized clinical trial aimed at preventing poor psychosocial and glycemic outcomes in teens with type 1 diabetes (T1D). AB - Adolescents with type 1 diabetes have an increased risk for a variety of emotional and behavioral challenges as well as negative diabetes outcomes. This study was designed to compare the effectiveness of a depression-prevention, resilience promotion program with an advanced diabetes education program. Each program consisted of 9 group-based sessions. There were 264 adolescents enrolled in this multi-site randomized clinical trial. The primary outcomes were depressive symptoms and glycemic control; secondary outcomes included resilience skills, diabetes management and adherence, and diabetes-specific distress. The goal of the present paper is to describe the study design, the intervention, and the baseline characteristics of the sample. Preliminary data suggests that enrollment, randomization and retention were successful. Longitudinal follow-up and examination of mechanisms of action as they relate to psychosocial and glycemic outcomes will be explored in the future. PMID- 27267158 TI - Geological and physicochemical controls of the spatial distribution of partition coefficients for radionuclides (Sr-90, Cs-137, Co-60, Pu-239,240 and Am-241) at a site of nuclear reactors and radioactive waste disposal (St. Petersburg region, Russian Federation). AB - The paper presents a study of the sorption properties of sediments of different geological ages and lithological types, governing radionuclide retention in the subsurface (up to 160 m beneath the surface) within the area of potential influence of the Northwestern Center of Atomic Energy (NWCAE), St. Petersburg region, RF. The focus of this work is mostly on the sedimentary rocks of two types, i.e., weakly cemented sandstone and lithified clay formations of Cambrian and Vendian series. The first lithological unit is associated with a groundwater reservoir (Lomonosov aquifer), and the second one, with both a relative aquitard in the upper part of the Vendian formation (Kotlin clay) and a regional aquifer (Gdov aquifer) in the lower part of the formation. The main mechanisms responsible for the variability of the sorption distribution coefficient (Kd, defined as the ratio of the concentration of solute on solid phase to its concentration in solution at equilibrium) was identified for radionuclides such as Sr-90, Cs-137, Co-60, Pu-239,240, and Am-241. It was shown that the main factors contributing to the chemical heterogeneity of the Cambrian sandstone were related to the presence of secondary minerals (iron and magnesium oxides and hydroxides produced by the weathering process) in trace amounts, forming correlated layer structures. The statistical analysis of nonlinear isotherms confirmed this conclusion. For the Vendian formation, a determinate trend was established in the Kd change over depth as a result of temporal trends in the sedimentation process and pore-water chemistry. The geostatistical characteristics and the spatial correlation models for describing linear sorption of different radionuclides are not identical, and the exhibition of chemical heterogeneity of sedimentary rock of a particular lithological type depends on radionuclide chemistry. Moreover, variogram analysis for some Kd data sets (both in Cambrian and Vendian formations) demonstrates the total absence of auto correlation (pure nugget effect). It can be supposed that sampling distances did not allow the evaluation of small-scale variability in sediment sorption properties. PMID- 27267159 TI - Accuracy associated with the activity determination by in situ gamma spectrometry of naturally occurring radionuclides in soils. AB - In situ gamma spectrometry (ISGS) is a technique mainly focused on the determination of man-made radionuclides deposited on soils. It is widely used for the radioactive characterization of soils in which there has been an incorporation of such radionuclides, especially 137Cs. Its use for the activity determination of naturally occurring radionuclides in soils has been more limited, and the accuracy associated with those measurements has yet to be treated extensively. There are numerous factors affecting the accuracy of the activity determination of naturally occurring radionuclides, such as the assumed soil geometry, the soil's geological and mineral composition, its moisture content, etc. The present work studies the accuracy associated with the ISGS determination of the activity concentrations of natural radionuclides in soils using a portable HPGe detector. For 40K and 232Th activity determinations, the uncertainties associated with ISGS are generally of the order of 15%. However, 226Ra activity determined from its daughters 214Pb and 214Bi can be significantly overestimated when there is a major presence of 222Rn in the air around the detector. Finally, absorbed dose rate in air values were calculated from the naturally occurring radionuclide concentration in soils. The results showed good correspondence between the values obtained from ISGS and those obtained from laboratory determinations with the same soils. PMID- 27267160 TI - Mid-range atmospheric dispersion modelling. Intercomparison of simple models in EMRAS-2 project. AB - An intercomparison of atmospheric dispersion models has been carried out for a hypothetical accident occurring in a nuclear power plant in the center of Spain. The accident consisted of a steam generator tube rupture, and two radionuclides have been considered for the exercise: 137-Cs and 131-I. Meteorological conditions and radionuclide release rates were supplied. Models provided deposition maps, timeintegrated concentrations in air and arrival times of the plumes to specific locations. The effect of the meteorological conditions used in the modelling was clear, with different behavior of the plume with neutral stability vs. stable conditions. The predicted arrival times of the plume at specific locations showed much less variability than deposition and air concentrations. This variability in part reflects the uncertainties inherent in atmospheric dispersion modelling and in the selection of parameter values, such as deposition velocities or diffusivities. PMID- 27267161 TI - How does C/EBPalpha speed up cell reprogramming? PMID- 27267162 TI - The historical path of evaluation as reflected in the content of Evaluation and Program Planning. AB - This paper examines the intellectual structure of evaluation by means of citation analysis. By using various article attributes and citation counts in Google Scholar and (Social) Science Citation Index Web of Science, we analyze all articles published in Evaluation and Program Planning from 2000 until 2012. We identify and discuss the characteristics and development of the field as reflected in the history of those citations. PMID- 27267163 TI - Genetic susceptibility to rheumatoid arthritis and its implications for novel drug discovery. AB - INTRODUCTION: Over 100 susceptibility loci have now been identified for rheumatoid arthritis (RA), several of which are already the targets of approved RA therapies providing proof of concept for the use of genetics in novel drug development for RA. Determining how these loci contribute to disease will be key to elucidating the mechanisms driving disease development, which has the potential for major impact on therapeutic development. AREAS COVERED: Here the authors review the use of genetics in drug discovery, including the use of 'omics' data to prioritise potential drug targets at susceptibility loci using RA as an exemplar. They discuss the current state of RA genetics its impact on stratified medicine, and how the findings from RA genetics studies can be used to inform drug discovery. EXPERT OPINION: It is anticipated that functional characterisation of disease variants will provide biological validation of a gene as a drug target, providing safer targets, with an increased likelihood of efficacy. In the future, techniques such as genome editing may represent a plausible option for RA therapy. Technologies such as genome-wide chromatin conformation capture Hi-C and CRISPR will be crucial to inform our understanding of how diseases develop and in developing new treatments. PMID- 27267168 TI - The Causes of the Scientific and Regulatory Gap in the Listing of New Persistent Organic Pollutants into the Stockholm Convention. PMID- 27267167 TI - Estimation of the Pressure Drop Required for Lymph Flow through Initial Lymphatic Networks. AB - BACKGROUND: Lymphatic function is critical for maintaining interstitial fluid balance and is linked to multiple pathological conditions. While smooth muscle contractile mechanisms responsible for fluid flow through collecting lymphatic vessels are well studied, how fluid flows into and through initial lymphatic networks remains poorly understood. The objective of this study was to estimate the pressure difference needed for flow through an intact initial lymphatic network. METHODS AND RESULTS: Pressure drops were computed for real and theoretical networks with varying branch orders using a segmental Poiseuille flow model. Vessel geometries per branch order were based on measurements from adult Wistar rat mesenteric initial lymphatic networks. For computational predications based on real network geometries and combinations of low or high output velocities (2 mm/s, 4 mm/s) and viscosities (1 cp, 1.5 cp), pressure drops were estimated to range 0.31-2.57 mmHg. The anatomical data for the real networks were also used to create a set of theoretical networks in order to identify possible minimum and maximum pressure drops. The pressure difference range for the theoretical networks was 0.16-3.16 mmHg. CONCLUSIONS: The results support the possibility for suction pressures generated from cyclic smooth muscle contractions of upstream collecting lymphatics being sufficient for fluid flow through an initial lymphatic network. PMID- 27267169 TI - A Combination of Buccal Plate Preservation and Dual Zone Therapeutic Technique in Immediate Implants: A One-Year Follow-Up. PMID- 27267171 TI - Identifying and assessing highly hazardous drugs within quality risk management programs. AB - Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs. PMID- 27267172 TI - A harmonization effort for acceptable daily exposure application to pharmaceutical manufacturing - Operational considerations. AB - A European Union (EU) regulatory guideline came into effect for all new pharmaceutical products on June 1st, 2015, and for all existing pharmaceutical products on December 1st, 2015. This guideline centers around the use of the Acceptable Daily Exposure (ADE) [synonymous with the Permitted Daily Exposure (PDE)] and operational considerations associated with implementation are outlined here. The EU guidance states that all active pharmaceutical ingredients (API) require an ADE; however, other substances such as starting materials, process intermediates, and cleaning agents may benefit from an ADE. Problems in setting ADEs for these additional substances typically relate to toxicological data limitations precluding the ability to establish a formal ADE. Established methodologies such as occupational exposure limits or bands (OELs or OEBs) and the threshold of toxicological concern (TTC) can be used or adjusted for use as interim ADEs when only limited data are available and until a more formal ADE can be established. Once formal ADEs are derived, it is important that the documents are routinely updated and that these updates are communicated to appropriate stakeholders. Another key operational consideration related to data-poor substances includes the use of maximum daily dose (MDD) in setting cross contamination limits. The MDD is an important part of the maximum allowable/safe concentration (MAC/MSC) calculation and there are important considerations for its use and definition. Finally, other considerations discussed include operational aspects of setting ADEs for pediatrics, considerations for large molecules, and risk management in shared facilities. PMID- 27267173 TI - Multiblock Copolymer Grafting for Butanol Biofuel Recovery by a Sustainable Membrane Process. AB - Biobutanol is an attractive renewable biofuel mainly obtained by the acetone butanol-ethanol (ABE) fermentation process. Nevertheless, the alcohol concentration has to be limited to a maximum of 2 wt % in ABE fermentation broths to avoid butanol toxicity to the microorganisms. The pervaporation (PV) membrane process is a key sustainable technology for butanol recovery in these challenging conditions. In this work, the grafting of azido-polydimethylsiloxane (PDMS-N3) onto a PDMS-based multiblock copolymer containing alkyne side groups led to a series of original membrane materials with increasing PDMS contents from 50 to 71 wt %. Their membrane properties were assessed for butanol recovery by pervaporation from a model aqueous solution containing 2 wt % of n-butanol at 50 degrees C. The membrane flux J50MUm for a reference thickness of 50 MUm strongly increased from 84 to 192 g/h m(2) with increasing PDMS content for free-standing dense membranes with thicknesses in the range of 38-95 MUm. At the same time, the intrinsic butanol permeability increased from 1.47 to 4.68 kg MUm/h m(2) kPa and the permeate butanol content was also strongly improved from 38 to 53 wt %, corresponding to high and very high membrane separation factors of 30 and 55, respectively. Therefore, the new grafted copolymer materials strongly overcame the common permeability/selectivity trade-off for butanol recovery by a sustainable membrane process. PMID- 27267174 TI - Decreasing the required lumbar extensor moment induces earlier onset of flexion relaxation. AB - Flexion relaxation (FR) is characterized by the lumbar erector spinae (LES) becoming myoelectrically silent near full trunk flexion. This study was designed to: (1) determine if decreasing the lumbar moment during flexion would induce FR to occur earlier; (2) characterize thoracic and abdominal muscle activity during FR. Ten male participants performed four trunk flexion/extension movement conditions; lumbar moment was altered by attaching 0, 5, 10, or 15lb counterweights to the torso. Electromyography (EMG) was recorded from eight trunk muscles. Lumbar moment, lumbar flexion and trunk inclination angles were calculated at the critical point of LES inactivation (CPLES). Results demonstrated that counterweights decreased the lumbar moment and lumbar flexion angle at CPLES (p<0.0001 and p=0.0029, respectively); the hypothesis that FR occurs earlier when lumbar moment is reduced was accepted. The counterweights did not alter trunk inclination at CPLES (p=0.1987); this is believed to result from an altered hip to spine flexion ratio when counterweights were attached. Lumbar multifidus demonstrated FR, similar to LES, while thoracic muscles remained active throughout flexion. Abdominal muscles activated at the same instant as CPLES, except in the 15lb condition where abdominal muscles activated before CPLES resulting in a period of increased co-contraction. PMID- 27267175 TI - Ultrasonographic caval indices do not significantly contribute to predicting fluid responsiveness immediately after coronary artery bypass grafting when compared to passive leg raising. AB - BACKGROUND: Appropriate fluid management is one of the most important elements of early goal-directed therapy after cardiothoracic surgery. Reliable determination of fluid responsivenss remains the fundamental issue in volume therapy. The purpose of the study was to assess the usefulness of dynamic IVC-derived parameters (collapsibility index, distensibility index) in comparison to passive leg raising, in postoperative fluid management in mechanically ventilated patients with left ventricular ejection fraction >= 30 %, immediately after elective coronary artery bypass grafting. METHODS: Prospective observational case series study including 35 patients with LVEF >= 30 %, undergoingelective coronary artery bypass grafting was conducted. Transthoracic echocardiography, passive leg raising and intravenous administration of saline were performed in all study subjects. Dynamic parameters derived from ultrasonographic assessment of the IVC diameter (collapsibility index-CI and distensibility index-DI), cardiac output RESULTS: There were 24 (68.57 %) responders in the study population. There were no statistical differences between the groups in relation to: clinical parameters, pre- and postoperative LVEF, fluid balance and CVP. Change in cardiac output after passive leg raising correlated significantly with that after the volume expansion (p=0.000, r=0.822). Dynamic IVC derivatives were slightly higher in fluid responders, however this trend did not reach statistical significance. None of the caval indices correlated with fluid responsiveness. CONCLUSION: Dynamic IVC-derived parameters do not predict fluid responsiveness in mechanically ventilated patients with preserved ejection fraction immediately after elective coronary artery bypass grafting. Passive leg raising is not inferior to volume expansion in differentiating between fluid responders and nonresponders. Immediate fluid challenge after CABG is safe and well tolerated. PMID- 27267176 TI - Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid. AB - BACKGROUND: The defining feature of the cerebrospinal fluid (CSF) collected from infants and children with tuberculous meningitis (TBM), derived from an earlier untargeted nuclear magnetic resonance (NMR) metabolomics study, was highly elevated lactic acid. Undetermined was the contribution from host response (L lactic acid) or of microbial origin (D-lactic acid), which was set out to be determined in this study. METHODS: In this follow-up study, we used targeted ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to determine the ratio of the L and D enantiomers of lactic acid in these CSF samples. RESULTS: Here we report for the first time that the lactic acid observed in the CSF of confirmed TBM cases was in the L-form and solely a response from the host to the infection, with no contribution from any bacteria. The significance of elevated lactic acid in TBM appears to be that it is a crucial energy substrate, used preferentially over glucose by microglia, and exhibits neuroprotective capabilities. CONCLUSION: These results provide experimental evidence to support our conceptual astrocyte-microglia lactate shuttle model formulated from our previous NMR-based metabolomics study - highlighting the fact that lactic acid plays an important role in neuroinflammatory diseases such as TBM. Furthermore, this study reinforces our belief that the determination of enantiomers of metabolites corresponding to infectious diseases is of critical importance in substantiating the clinical significance of disease markers. PMID- 27267178 TI - Access to Structurally Diverse Quinoline-Fused Heterocycles via Rhodium(III) Catalyzed C-C/C-N Coupling of Bifunctional Substrates. AB - Rhodium(III)-catalyzed C-H activation of heteroarenes and functionalization with bifunctional substrates such as anthranils allows facile construction of quinoline-fused heterocycles under redox-neutral conditions. The couplings feature broad substrate scope and provide step-economical access to two classes of quinoline-fused condensed heterocycles. PMID- 27267177 TI - Selection of reliable reference genes for RT-qPCR studies in Octopus vulgaris paralarvae during development and immune-stimulation. AB - The common octopus, Octopus vulgaris is a new candidate species for aquaculture. However, rearing of octopus paralarvae is hampered by high mortality and poor growth rates that impede its entire culture. The study of genes involved in the octopus development and immune response capability could help to understand the key of paralarvae survival and thus, to complete the octopus life cycle. Quantitative real-time PCR (RT-qPCR) is the most frequently tool used to quantify the gene expression because of specificity and sensitivity. However, reliability of RT-qPCR requires the selection of appropriate normalization genes whose expression must be stable across the different experimental conditions of the study. Hence, the aim of the present work is to evaluate the stability of six candidate genes: beta-actin (ACT), elongation factor 1-alpha (EF), ubiquitin (UBI), beta-tubulin (TUB), glyceraldehyde 3-phosphate dehydrogenase (GADPH) and ribosomal RNA 18 (18S) in order to select the best reference gene. The stability of gene expression was analyzed using geNorm, NormFinder and Bestkeeper, in octopus paralarvae of seven developmental stages (embryo, paralarvae of 0, 10, 15, 20, 30 and 34days) and paralarvae of 20days after challenge with Vibrio lentus and Vibrio splendidus. The results were validated by measuring the expression of PGRP, a stimuli-specific gene. Our results showed UBI, EF and 18S as the most suitable reference genes during development of octopus paralarvae, and UBI, ACT and 18S for bacterial infection. These results provide a basis for further studies exploring molecular mechanism of their development and innate immune defense. PMID- 27267180 TI - Skin care in nursing: A critical discussion of nursing practice and research. AB - Skin (self-)care is part of human life from birth until death. Today many different skin care practices, preferences, traditions and routines exist in parallel. In addition, preventive and therapeutic skin care is delivered in nursing and healthcare by formal and informal caregivers. The aim of this contribution is a critical discussion about skin care in the context of professional nursing practice. An explicit skin assessment using accurate diagnostic statements is needed for clinical decision making. Special attention should be paid on high risk skin areas, which may be either too dry or too moist. From a safety perspective the protection and maintenance of skin integrity should have the highest priority. Skin cleansing is the removal of unwanted substances from the skin surface. Despite cleansing efficacy soap, other surfactants and water will inevitably always result in the destruction of the skin barrier. Thousands of products are available to hydrate, moisturize, protect and restore skin properties dependent upon their formulation and the concentration of ingredients. These products intended to left in contact with skin exhibit several actions on and in the skin interfering with skin biology. Unwanted side effects include hyper-hydration and disorganization of lipid bilayers in the stratum corneum, a dysfunctional barrier, increased susceptibility to irritants and allergies, and increases of skin surface pH. Where the skin barrier is impaired appropriate interventions, e.g. apply lipophilic products in sufficient quantity to treat dry skin or protect the skin from exposure to irritants should be provided. A key statement of this contribution is: every skin care activity matters. Every time something is placed on the skin, a functional and structural response is provoked. This response can be either desired or undesired, beneficial or harmful. The choice of all skin care interventions in nursing and healthcare practice must be based on an accurate assessment of the skin and concomitant health conditions and on a clearly defined outcome. A standardized skin care and skin care product language is needed for researchers planning and conducting clinical trials, for reviewers doing systematic reviews and evidence base summaries, for nurses and other healthcare workers to deliver evidence-based and safe skin care. PMID- 27267179 TI - Analysis of the virulence-associated RevSR two-component signal transduction system of Clostridium perfringens. AB - Clostridium perfringens is a Gram-positive, anaerobic, spore-forming bacterium that causes human gas gangrene (clostridial myonecrosis) and food poisoning. Early studies showed that virulence was regulated by the VirSR two-component signal transduction system. However, our identification of the RevR orphan response regulator indicated that more than one system was involved in controlling virulence. To further characterize this virulence-associated regulator, gel mobility shift experiments, coupled with DNase I footprinting, were used to identify the RevR DNA binding sequence. Bioinformatics analysis suggested that an orphan sensor histidine kinase, CPE1757 (renamed RevS), was the cognate sensor of RevR. Interaction between RevS and RevR was demonstrated by use of a bacterial two-hybrid system and validated by protein-protein interaction studies using biolayer interferometry. To assess the involvement of RevS in virulence regulation, the revS gene was inactivated by Targetron insertion. When isogenic wild-type, revS and complemented revS strains were tested in a mouse myonecrosis model, the revS mutant was found to be attenuated in virulence, which was similar to the attenuation observed previously with the revR mutant. However, transcriptional analysis of selected RevR-regulated genes in the revS mutant revealed a different pattern of expression to a revR mutant, suggesting that the RevSR system is more complex than originally thought. Taken together, the results have led to the identification and characterization of the two essential parts of a new regulatory network that is involved in the regulation of virulence in C. perfringens. PMID- 27267181 TI - The effectiveness and experience of self-management following acute coronary syndrome: A review of the literature. AB - OBJECTIVES: To evaluate the effectiveness of interventions used to support self management, and to explore patients' experiences after acute coronary syndrome in relation to self-management. DESIGN: Scoping review. DATA SOURCES: Keyword search of CINAHL Plus, Medline, the Cochrane Library, and PsycINFO databases for studies conducted with adult population and published in English between 1993 and 2014. REVIEW METHODS: From title and abstract review, duplicated articles and obviously irrelevant studies were removed. The full texts of the remaining articles were assessed against the selection criteria. Studies were included if they were original research on: (1) effectiveness of self-management interventions among individuals following acute coronary syndrome; or (2) patients' experience of self-managing recovery from acute coronary syndrome. RESULTS: 44 articles (19 quantitative and 25 qualitative) were included. Most studies were conducted in western countries and quantitative studies were UK centric. Self-management interventions tended to be complex and include several components, including education and counselling, goal setting and problem solving skills which were mainly professional-led rather than patient-led. The review demonstrated variation in the effectiveness of self-management interventions in main outcomes assessed - anxiety and depression, quality of life and health behavioural outcomes. For most participants in the qualitative studies, acute coronary syndrome was unexpected and the recovery trajectory was a complex process. Experiences of making adjustment and adopting lifestyle changes following acute coronary syndrome were influenced by subjective life experiences and individual, sociocultural and environmental contexts. Participants' misunderstandings, misconceptions and confusion about disease processes and management were another influential factor. They emphasised a need for ongoing input and continued support from health professionals in their self-management of rehabilitation and recovery, particularly during the initial recovery period following hospital discharge. CONCLUSIONS: Evidence of the effectiveness of self-management interventions among people with acute coronary syndrome remains inconclusive. Findings from the patients' experiences in relation to self-management following acute coronary syndrome provided important insights into what problems patients might have encountered during self-managing recovery and what support they might need, which can be used to inform the development of self-management interventions. Theoretical or conceptual frameworks have been minimally employed in these studies and should be incorporated in future development and evaluation of self-management interventions as a way of ensuring clarity and consistency related to how interventions are conceptualised, operationalised and empirically studied. Further research is needed to evaluate self-management interventions among people following acute coronary syndrome for sustained effect and within different health care contexts. PMID- 27267182 TI - Protocol for a prospective observational study of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy. AB - BACKGROUND: Cerebral palsy leads to many complications as well as delayed motor development, and early intensive rehabilitation in infancy, which is based on the theory of brain plasticity, is emphasized. In addition to conventional treatment, including physical, occupational, or speech-language therapies, children also have a demand for traditional Korean medicine interventions such as acupuncture or herbal medicine; however, a lack of evidence has made traditional Korean medicine difficult to implement in practice. We planned a multicentre, prospective, observational study to assess the effectiveness, safety and cost effectiveness of conventional treatment and traditional Korean medicine combination treatment for children with cerebral palsy. METHODS/DESIGN: Three hundred children with cerebral palsy aged 6 to 78 months will be recruited from six institutions. Data from each child are collected every month for a one-year period, during which time treatment might be changed or discontinued. A qualified investigator visits the sites to measure effectiveness variables, including Gross Motor Function Measure and Paediatric Evaluation of Disability Inventory. Adverse events and cost-effectiveness variables are collected using surveys conducted at baseline, mid-study, and end of study, as well as monthly tracking surveys. In the analyses, participants will be classified into two groups: group A children will be the conventional treatment group with physical, occupational, speech language or other conventional rehabilitation therapies, whereas group B children will be the combination treatment group with traditional Korean medicine interventions, that is, herbal medicine, chuna, moxibustion and acupuncture, in addition to conventional treatment. DISCUSSION: Only a few clinical case reports have evaluated the effectiveness and safety of traditional Korean medicine; therefore, more data are required to provide optimal information to children with cerebral palsy and their guardians. We hypothesized that traditional Korean medicine combination treatment for children with cerebral palsy would have benefits compared with conventional therapy alone. The findings of this study might provide informative data for conducting economic evaluations and developing clinical research on combination treatment for cerebral palsy in South Korea. TRIAL REGISTRATION: NCT02223741. PMID- 27267183 TI - Sulfate as a pivotal factor in regulation of Serratia sp. strain S2B pigment biosynthesis. AB - In the present work, we investigated the prodiginine family as secondary metabolite members. Bacterial strain S2B, with the ability to produce red pigment, was isolated from the Sarcheshmeh copper mine in Iran. 16S rDNA gene sequencing revealed that the strain was placed in the Serratia genus. Pigment production was optimized using low-cost culture medium and the effects of various physicochemical factors were studied via statistical approaches. Purification of the produced pigment by silica gel column chromatography showed a strong red pigment fraction and a weaker orange band. Mass spectrometry, FT-IR spectroscopy and (1)H NMR analysis revealed that the red pigment was prodigiosin and the orange band was a prodigiosin-like analog, with molecular weights of 323 and 317 Da, respectively. Genotoxicity and cytotoxicity studies confirmed their membership in the prodiginine family. Analysis of the production pattern of the pigments in the presence of different concentrations of ammonium salts revealed the role of sulfate as an important factor in regulation of the pigment biosynthesis pathway. Overall, the data showed that regulation of the pigment biosynthesis pathway in Serratia sp. strain S2B was affected by inorganic micronutrients, particularly the sulfate ions. PMID- 27267184 TI - Proximal nailfold microhemorrhage events are manifested as distal cuticular (eponychial) hemosiderin-containing deposits (CEHD) (syn. Maricq sign) and can aid in the diagnosis of dermatomyositis and systemic sclerosis. AB - IMPORTANCE: Many patients present with cutaneous signs and symptoms that suggest a diagnosis on the autoimmune disease spectrum. During the "acute phase" of disease activity, patients with systemic sclerosis (SSc) and dermatomyositis (DM) have characteristic nailfold findings, including dilated capillaries, microhemorrhages, and hemosiderin deposits. OBJECTIVE: To review the literature on the presentation of microhemorrhages and to highlight the differences (in terms of terminology, characterization, and clinical relevance) between proximal microhemorrhage events and the distal products, often thought of as "hemosiderin deposits" located in the cuticle (eponychium). Because we found no studies directly showing these cuticular products are in fact "hemosiderin-containing," we conducted a direct staining experiment in vivo using Prussian blue in order to increase our confidence that these products are indeed hemosiderin-containing and that the terminology is accurate for further use. EVIDENCE REVIEW: In July December 2014, the MeSH function in PubMed was used to identify approximately 165 articles relating to capillaroscopy. We reviewed these articles for mention of microhemorrhages and hemosiderin deposits. In addition, we used PubMed and Google Scholar searches for "hemosiderin + nail", "Prussian Blue + nail", and "hemosiderin deposit." We found no papers reporting the use of Prussian Blue directly on nailfolds of patients with SSc and DM in vivo. FINDINGS: In our literature review, "microhemorrhages" and "hemosiderin deposits" were often used synonymously, yet they are clearly distinct entities. We present a case in which the presence of these deposits supported a diagnosis of amyopathic DM. We used Prussian blue staining solution to visualize the cuticular (eponychial) hemosoderin-containing deposits (CEHD) - distal cuticular products that reflect previous proximal nailfold microhemorrhage events. CEHD can serve as an indicator of active autoimmune disease, particularly in SSc and DM. CONCLUSIONS AND RELEVANCE: CEHD are in fact hemosiderin-containing deposits that can reflect the active inflammatory phase of microvascular injury occuring in autoimmune disorders such as DM and SSc. CEHD can be visualized and documented at the bedside with tools commonly available to any dermatologist (portable dermatoscope and compact digital camera). PMID- 27267185 TI - Update on treatment of photodermatosis. AB - Photodermatoses are a group of skin conditions associated with an abnormal reaction to ultraviolet (UV) radiation. There are several of the photosensitive rashes which mainly affect the UV exposed areas of the skin. It can be classified into four groups: immunology mediated photodermatoses, chemical and drug induced photosensitivity, photoaggravated dermatoses, and genetic disorders. A systematic approach including history, physical examination, phototesting, photopatch testing, and laboratory tests are important in diagnosis of a photodermatosis patient. In order to optimally treat a disease of photodermatoses, we need to consider which treatment offers the most appropriate result in each disease, such as sunscreens, systemic medication, topical medication, phototherapy, and others. For all groups of photodermatoses, photoprotection is one of the essential parts of management. Photoprotection, which includes sunscreening and wearing photoprotective clothing, a wide brimmed hat, and sunglasses, is important. There are also promising emerging photoprotective agents. PMID- 27267186 TI - Patient satisfaction with current psoriasis treatment: a real-world study in the USA. AB - Psoriasis patients often report dissatisfaction with treatment. However, it is less clear how the severity of key psoriasis symptoms (painful skin, itching, and scaling) as well as overall disease severity influence patient dissatisfaction levels. Using the Adelphi 2011/2013 Psoriasis Disease Specific Programmes, two "real world" surveys of US dermatologists and their patients, patient satisfaction was evaluated. Dermatologists provided data on disease characteristics, while patients indicated their satisfaction with existing treatment. Physician-reported severity (none, mild, moderate/severe) of psoriasis related itching, pain, and scaling, overall disease severity (mild, moderate and severe) and therapy type were compared by patient satisfaction levels (satisfied vs. dissatisfied). Multivariate regressions examined the relationship between patient satisfaction, clinical symptoms, and psoriasis overall disease severity, controlling for differences in patient demographics and comorbidities. The sample comprised 633 psoriasis patients (56% male) with a mean age of 45. Overall, 18% of patients reported dissatisfaction with their psoriasis treatment. Dissatisfied patients were more likely to have moderate (65% vs. 40%) or severe (21% vs 3%) psoriasis compared to patients who were satisfied (both p<0.05). Dissatisfied patients were also more likely to have more severe pain (30% moderate-to-severe pain vs. 9%), more severe itching (61% moderate-to-severe itching vs. 25%), and more severe scaling (68% moderate-to-severe scaling vs. 33%) than satisfied patients (all p< 0.05). Multivariate analyses confirmed these results. Clinicians should be aware that some psoriasis patients, especially those with severe overall disease or symptoms, may be dissatisfied and are in need of better treatment. PMID- 27267187 TI - Use of high frequency ultrasonography in dermatology departments in Spain. AB - BACKGROUND: High Frequency Ultrasonography (HFUS) is a rapid, reliable, and effective diagnostic technique that has become progressively employed within the past years among dermatologists. OBJECTIVE: To describe the use of HFUS among dermatology departments in Spain. METHODS: An observational, cross-sectional descriptive study was conducted in 23 dermatology departments at Spanish public hospitals. Study data was collected during 10 working days. RESULTS: Fifty dermatologists from 11 Spanish regions participated in the study; 659 HFUS procedures were undertaken in 633 patients. HFUS indications were benign tumors (41%), malignant tumors (28%), inflammatory diseases (18%), skin appendage conditions (10%), and cosmetic conditions (1%). HFUS was performed for assessing the clinical differential diagnosis (58% of cases), surgical planning (17%), follow-up (17%), and other reasons (7%). Among the diagnostic group, the scan confirmed clinical diagnosis in 82% of cases and helped to change the clinical diagnosis in 17% cases (10% of total scans). HFUS procedure duration was less than 5 minutes (45%), between 5 and 10 minutes (32%), and more than 10 minutes (21%). Mean patient satisfaction score (range 0 to 5) was 4.8. CONCLUSIONS: The use of HFUS in usual practice is increasing, especially among younger dermatologists. This procedure is effective both for confirming and changing diagnosis, as well as for therapy decision making and follow-up. It is also worth remarking that a very high degree of patient satisfaction was recorded. The descriptive results reported in this study support the use of ultrasonography techniques and further reinforce their use in Dermatology. PMID- 27267188 TI - Dermatology in Doximity. AB - Doximity, currently the largest online social networking service for United States (US) health care professionals and medical students, provides a wide variety of content to a large audience. In fact, its database includes 1,078,305 physicians in the US. It is therefore important to evaluate this content from time to time. Our objective is to analyze both the residency rankings and news content presented in Doximity, with respect to dermatology. The study compared the residency rankings created by Doximity to another dermatology residency ranking system that used a different algorithm. In terms of dermatology content, seven dermatology-related search terms were entered into the Doximity search query and data was collected on the first 20 "relevant" articles. Our study evaluated a total of 140 articles. The search term "skin cancer" yielded the most articles totaling 6,001. Informative articles were the most common type of article for each content item searched except for "dermatology", yielding research articles as the most common content type (70%). The search term "melanoma awareness" had the largest number of shares (19,032). In comparing dermatology residency rankings on Doximity with another ranking system that accounted for scholarly achievement, there was 50% overlap. In conclusion, it is vital to evaluate content on social media websites that are utilized by US medical students and health care professionals. We hope this information presented provides an up-to-date analysis on the quality of one particular social media platform. PMID- 27267189 TI - Amitriptyline-induced cutaneous hyperpigmentation: case report and review of psychotropic drug-associated mucocutaneous hyperpigmentation. AB - BACKGROUND: Several drugs can be associated with hyperpigmentation of mucosa or skin. They include antibiotic, antimalarial, antineoplastic, and psychotropic medications. PURPOSE: To describe a 42-year-old woman with amitriptyline associated photo-distributed hyperpigmentation and to review psychotropic drug induced hyperpigmentation of the skin. MATERIALS AND METHODS: The features of a woman with amitriptyline-induced hyperpigmentation are presented. Using PubMed, the following terms were searched and relevant citations were assessed and discussed for context: amitriptyline, chlorpromazine, citalopram, desipramine, drug-associated, drug-induced, Fontana Masson, hyperpigmentation, imipramine, melanin, melanophages, mirtazapine, phenytoin, psychotropic, sertraline, thioridazine, tricyclic antidepressant. RESULTS: Photo-distributed hyperpigmentation on the upper back of a woman developed six and a half years after initiation of amitriptyline therapy. Biopsy of the affected area showed pigment-laden melanophages and intradermal melanin deposition. CONCLUSIONS: Psychotropic drugs associated with cutaneous hyperpigmentation include amitriptyline, chlorpromazine, citalopram, desipramine, imipramine, mirtazapine, phenytoin, sertraline, and thioridazine. The hyperpigmentation may initially appear many years after starting the medication. Pathology typically shows melanophages and melanin in the dermis. Fontana Masson stain confirms the presence of melanin; Perl stain for hemosiderin or iron is negative. Discontinuation of the drug may result in spontaneous improvement. Further studies are needed to better understand the role of Q-switched laser in treating drug-induced hyperpigmentation. PMID- 27267190 TI - An uncommon presentation of an uncommon disease: relapsing polychondritis overlap with systemic lupus erythematosus. AB - Relapsing polychondritis (RP) is a rare rheumatologic disorder in which recurrent episodes of inflammation result in destruction of cartilage of the ears and nose. The joints, eyes, audio-vestibular system, heart valves, respiratory tract, kidneys, and skin can also be involved. Skin involvement is most frequently linked to concomitant myelodysplastic syndrome and has rarely been associated with systemic lupus erythematosus. A 47-year-old woman presented with violaceous, indurated, tender plaques on the bilateral cartilaginous ears with sparing of the lobes, consistent with RP. Further investigations revealed positive ANA and anti Smith antibody, oral ulcers, a photo-distributed skin eruption, and biopsy-proven lupus nephritis, leading to a second concomitant diagnosis of systemic lupus erythematosus (SLE). The diagnosis of SLE associated with RP was made and the patient was started on oral prednisone and hydroxychloroquine. This is a rare report of SLE associated with RP. It is unclear whether RP occurring in patients with SLE represents another clinical manifestation of SLE or a coexisting disease. However, a significant ANA titer in a patient with RP strongly suggests the presence of an associated autoimmune disorder. If immunologic abnormalities usually found in SLE are detected in patients with RP, it is important to monitor patients for the development of other manifestations of SLE. PMID- 27267191 TI - Wade histoid leprosy revisited. AB - An 18-year-old man presented with a 4-year history of erythematous patches on the trunk, followed 2-years later by multiple nodules, mostly located on the limbs, and distal paresthesias. Two close contacts were treated for leprosy during his childhood. Histopathological examination revealed a histiocytic infiltrate with acid-fast bacilli on Ziehl-Neelsen stain. The slit-skin and nasal smears showed numerous acid-fast bacilli. The correlation between clinical, epidemiological, histopathological, and microbiological features allowed the diagnosis of lepromatous leprosy, histoid variant. Multidrug therapy as recommended by the WHO was initiated. A rapid and sustained improvement was seen. Histoid leprosy is a rare manifestation of lepromatous leprosy, first described by Wade in 1960. Since then few cases have been reported, the majority of them from countries with a high prevalence of the disease. Early recognition and treatment are of most importance to prevent neurological disabilities and achieve epidemiological control. PMID- 27267192 TI - Progeria and the early aging in children: a case report. AB - The Hutchinson-Gilford syndrome or progeria is a rare autosomal dominant syndrome characterized by premature aging and involvement of internal systems, such as the circulatory and locomotor. The diagnosis is essentially clinical and the manifestations become more evident from the first year of life. Long term outcome data from Progeria Research Foundation clinical trials have demonstrated an increase in survival in recent years. Even though new trials are ongoing, the recognition of this syndrome is essential to prevent cardiovascular and cerebrovascular complications. A patient, initially asymptomatic, who developed characteristic signs of the syndrome at the age of 6 months is reported. She was referred for evaluation only when she was two years and eleven months old. The diagnosis of Hutchinson-Gilford syndrome was suspected owing to clinical characteristics. The diagnosis was confirmed by genetic testing. A mutation c.1824C> T in exon 11 of the LMNA gene was detected. She was registered in the Progeria Research Foundation and was invited to participate in the weighing and supplementation program. She was included in the lonafarnib protocol study. This medication is a farnesyl transferase inhibitor that prevents the production of progerina and slows cardiovascular and neurological complications of the syndrome. This case highlights the importance of diagnosing progeria patients because they may be referred to the Progeria Research Foundation, which offers genetic screening and inclusion in clinical and therapeutic follow-up protocols without any costs. Progeria trials and research may also contribute to new drug developments related to prevention of aging and atherosclerosis in the near future. PMID- 27267193 TI - Generalized morphea as the first sign of breast carcinoma: a case report. AB - Generalized morphea is a rare idiopathic form of scleroderma that literally means "hard skin." Morphea is usually considered an isolated event that is not associated with malignancy. However, case reports of lung, hematologic, and breast cancer occurring simultaneously with large plaque morphea have caused dermatologists to question whether a work-up for malignancy is appropriate. We highlight a case of generalized morphea that preceded invasive ductal carcinoma of the breast and provide a discussion about the possible paraneoplastic origin of generalized morphea and systemic sclerosis (SSc). PMID- 27267194 TI - Neutrophilic dermatosis of the dorsal hands in an elderly man. AB - recently diagnosed with stage II lung adenocarcinoma, who presented to the clinic with a 14-day history of painful macules that progressed to bullae on the dorsal surface of his hands; decreased range of motion was noted. Examination revealed bilateral small, tender violaceous vesicopustules admixed with larger tense hemorrhagic pus-filled bullae on the dorsal aspect of his hands. Biopsy demonstrated changes consistent with neutrophilic dermatosis of the dorsal hands. The patient had been diagnosed with ulcerative colitis in the 1970s, although the condition was asymptomatic at the time of presentation. Treatment with prednisone 60 mg daily resulted in significant improvement by the next day. This regimen was continued for two weeks and was followed by a 6-week steroid taper. After a review of the approximate 75 cases currently reported, we also discuss the recurrence rate of NDDH of approximately 10%. PMID- 27267195 TI - Nevoid hyperkeratosis of the nipple and the areola. AB - A 25-year-old woman presented to our dermatology unit with progressive diffuse thickening of the both areolas. A skin biopsy was taken from the right areola showing irregular filiform acanthosis with elongation and anastomosis of rete ridges, irregular orthokeratotic hyperkeratosis, pseudocyst formation, and hyperpigmentation of the basal layer. The cause of nevoid hyperkeratosis of the nipple and areola is unknown. Eighty percent of cases occur in women and are often manifested during puberty or pregnancy. The disease may also occur in men receiving hormonal therapy. There is no uniformly effective treatment. Dermatologists, gynecologists, and general practitioners have an important part to play in recognizing this condition that may be underdiagnosed because of lack of awareness. PMID- 27267196 TI - Verrucous tumor mimicking squamous cell carcinoma in immunocompetent patient. AB - Mycobacteria cause a range of diseases in both immunocompetent and immunosuppressed individuals. An increase in non-tuberculous mycobacterial (NTM) infections targeting skin has been described. Many hypotheses have been developed in order to explain it: the increasing burden of immunocompromised individuals, immigration from endemic countries, improved laboratory identification techniques, and changes inhuman behavior that expose individuals to this NTM. Mycobacterium mucogenicum group comprises M. mucogenicum, Mycobacterium aubagnense, and Mycobacterium phocaicum. This group of organisms was first named Mycobacterium chelonae-like organism in 1982. Most clinically significant cases of those organisms involved catheter-related infections. Nevertheless, we report an interesting patient with a cutaneous infection produced by M. mucogenicum mimicking a squamous cell carcinoma; an excellent response to combined therapy with rifampicin and clarythromicin was observed. PMID- 27267197 TI - Dapsone for treatment of erythema nodosum. AB - Erythema Nodosum (EN) is the most common form of septal panniculitis, with over 100 reported infectious, malignant, inflammatory, idiopathic, and autoimmune causes. PMID- 27267198 TI - Multiple cutaneous lipomatous neurofibromas. AB - Cutaneous lipomatous neurofibroma is a rare variant of neurofibroma with a little known pathogenesis; its presence has never been described in Brazil. A 61- year old woman complaining scalp papules for one year, presented with skin colored to yellowish papules on the scalp. She noted that they were sometimes itchy and occasionally bled. Dermoscopy showed amorphous material, milky white, with a small poorly delimited yellowish area. Histopathological examination revealed spindle cell proliferation associated with mature adipocytes. Cutaneous lipomatous neurofibroma appears to be an underdiagnosed condition owing to the low index of suspicion and lack of knowledge of its existence. Few cases have been reported in the literature. PMID- 27267199 TI - Atypical rosacea in a male patient: case study. AB - Rosacea fulminans is a rare disorder of unknown cause, almost exclusively affecting women. There are only a few reported cases in men. The condition is characterized by the abrupt onset of pustules and nodules predominantly affecting the cheeks or chin without any systemic upset. We report the case of a 37-year old man who presented with papulopustules, predominantly localized to his nose. Histopathological features were consistent with rosacea fulminans. The patient was managed with treatments including oral prednisolone, isotretinoin, and trimethioprim. PMID- 27267200 TI - Transcriptome analysis of human brain tissue identifies reduced expression of complement complex C1Q Genes in Rett syndrome. AB - BACKGROUND: MECP2, the gene mutated in the majority of Rett syndrome cases, is a transcriptional regulator that can activate or repress transcription. Although the transcription regulatory function of MECP2 has been known for over a decade, it remains unclear how transcriptional dysregulation leads to the neurodevelopmental disorder. Notably, little convergence was previously observed between the genes abnormally expressed in the brain of Rett syndrome mouse models and those identified in human studies. METHODS: Here we carried out a comprehensive transcriptome analysis of human brain tissue from Rett syndrome brain using both RNA-seq and microarrays. RESULTS: We identified over two hundred differentially expressed genes, and identified the complement C1Q complex genes (C1QA, C1QB and C1QC) as a point of convergence between gene expression changes in human and mouse Rett syndrome brain. CONCLUSIONS: The results of our study support a role for alterations in the expression level of C1Q complex genes in RTT pathogenesis. PMID- 27267201 TI - Prevention of Clostridium difficile Infection: A Systematic Survey of Clinical Practice Guidelines. AB - BACKGROUND Clostridium difficile infection (CDI) is the most common cause of hospital-acquired infectious diarrhea. OBJECTIVE To analyze the methodological quality, content, and supporting evidence among clinical practice guidelines (CPGs) on CDI prevention. DESIGN AND SETTING We searched medical databases and gray literature for CPGs on CDI prevention published January 2004-January 2015. Three reviewers independently screened articles and rated CPG quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument, composed of 23 items, rated 1-7, within 6 domains. We reported each domain score as a percentage of its maximum possible score and standardized range. We summarized recommendations, extracted their supporting articles, and rated individually the level of evidence using the Oxford Centre for Evidence-Based Medicine Levels of Evidence. RESULTS Of 2,578 articles screened, 5 guidelines met inclusion criteria. Median AGREE II scores and interquartile ranges were: clarity of presentation, 75.9% (75.9%-79.6%); scope and purpose, 74.1% (68.5%-85.2%); editorial independence, 63.9% (47.2%-66.7%); applicability, 43.1% (19.4%-55.6%); stakeholder involvement, 40.7% (38.9%-44.4%); and rigor of development, 18.1% (17.4%-35.4%). CPGs addressed several common strategies for CDI prevention, including antibiotic stewardship, hypochlorite solutions, probiotic prophylaxis, and bundle strategies. Recommendations were often not consistent with evidence, and most were based on low-level studies. CONCLUSION CPGs did not adhere well to AGREE II reporting standards. Furthermore, there was limited transparency in moving from evidence to recommendations. CDI prevention CPGs need to better adhere to AGREE-II and be transparent in moving from evidence to recommendations, and recommendations need to be consistent with available evidence. Infect Control Hosp Epidemiol 2016;37:901-908. PMID- 27267204 TI - Glyphosate and adverse pregnancy outcomes, a systematic review of observational studies. AB - BACKGROUND: A study in frog and chicken embryos, and reports of a high incidence of birth defects in regions of intensive GM-soy planting have raised concerns on the teratogenic potential of glyphosate-based herbicides. These public concerns prompted us to conduct a systematic review of the epidemiological studies testing hypotheses of associations between glyphosate exposure and adverse pregnancy outcomes including birth defects. METHODS: A systematic and comprehensive literature search was performed in MEDLINE, TOXLINE, Bireme-BVS and SCOPUS databases using different combinations of exposure and outcome terms. A case control study on the association between pesticides and congenital malformations in areas of extensive GM soy crops in South America, and reports on the occurrence of birth defects in these regions were reviewed as well. RESULTS: The search found ten studies testing associations between glyphosate and birth defects, abortions, pre-term deliveries, small for gestational date births, childhood diseases or altered sex ratios. Two additional studies examined changes of time-to-pregnancy in glyphosate-exposed populations. Except for an excess of Attention Deficit Hyperactivity Disorder - ADHD (OR = 3.6, 1.3-9.6) among children born to glyphosate appliers, no significant associations between this herbicide and adverse pregnancy outcomes were described. Evidence that in South American regions of intensive GM-soy planting incidence of birth defects is high remains elusive. CONCLUSIONS: Current epidemiological evidence, albeit limited to a few studies using non-quantitative and indirect estimates and dichotomous analysis of exposures, does not lend support to public concerns that glyphosate based pesticides might pose developmental risks to the unborn child. Nonetheless, owing to methodological limitations of existing analytical observational studies, and particularly to a lack of a direct measurement (urine and/or blood levels), or an indirect estimation of exposure that has proven valid, these negative findings cannot be taken as definitive evidence that GLY, at current levels of occupational and environmental exposures, brings no risk for human development and reproduction. PMID- 27267202 TI - Long range physical cell-to-cell signalling via mitochondria inside membrane nanotubes: a hypothesis. AB - Coordinated interaction of single cells by cell-to-cell communication (signalling) enables complex behaviour necessary for the functioning of multicellular organisms. A quite newly discovered cell-to-cell signalling mechanism relies on nanotubular cell-co-cell connections, termed "membrane nanotubes" (MNTs). The present paper presents the hypothesis that mitochondria inside MNTs can form a connected structure (mitochondrial network) which enables the exchange of energy and signals between cells. It is proposed that two modes of energy and signal transmission may occur: electrical/electrochemical and electromagnetic (optical). Experimental work supporting the hypothesis is reviewed, and suggestions for future research regarding the discussed topic are given. PMID- 27267205 TI - Heterosexual practices of women and men living with HIV attending hospital outpatient services (ANRS-VESPA2 survey): a French comparative study with the general population (CSF survey). AB - HAART has improved the well-being of many people living with HIV (PLWH). This study aimed at (i) comparing heterosexual practices between PLWH and the general population by gender, and (ii) identifying factors associated with sexual practices and at-risk behaviors in the two populations. Self-reported data were collected among PLWH attending hospitals (VESPA2 survey; n = 3022) and the general population (CSF survey; n = 10,280). Significant differences between the two samples were corrected for by implementing propensity score matching on both socio-demographic characteristics and sexual behavior in terms of number of partners. Men not reporting heterosexual intercourse were excluded. After matching, 61% of women (out of 707) and 68% of men (out of 709) were sexually active in both populations. PLWH practiced oral sex less than the general population and used condoms more consistently over the previous 12-month period, irrespective of having multiple sexual partners or not. For women living with HIV: those with several sexual partners and those consuming drugs over the previous 12 months were more likely to practice oral sex; those living in a couple for at least 6 years and migrants were less likely to practice anal intercourse. For men living with HIV: those reporting bisexual relationships and those with multiple sexual partners over the previous 12 months were more likely to practice anal heterosexual intercourse; migrants reported less oral sex, irrespective of HIV status. Error term correlations showed that anal intercourse was not linked to condom use for women or men from either population. Our results show that PLWH had a lower rate of heterosexual practices compared with the general population, and used condoms more often, irrespective of the number of sexual partners and strong cultural background (e.g., for Sub-Saharan African women). Further preventive information needs to be disseminated on the risk of infection transmission through heterosexual anal intercourse. PMID- 27267203 TI - Questions regarding the safety and duration of immunity following live yellow fever vaccination. AB - INTRODUCTION: The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas covered: We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert commentary: Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered. PMID- 27267206 TI - Control and optimization in the modeling of fibrosis: Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by Martine Ben Amar and Carlo Bianca. PMID- 27267207 TI - Recursive Factorization of the Inverse Overlap Matrix in Linear-Scaling Quantum Molecular Dynamics Simulations. AB - We present a reduced complexity algorithm to compute the inverse overlap factors required to solve the generalized eigenvalue problem in a quantum-based molecular dynamics (MD) simulation. Our method is based on the recursive, iterative refinement of an initial guess of Z (inverse square root of the overlap matrix S). The initial guess of Z is obtained beforehand by using either an approximate divide-and-conquer technique or dynamical methods, propagated within an extended Lagrangian dynamics from previous MD time steps. With this formulation, we achieve long-term stability and energy conservation even under the incomplete, approximate, iterative refinement of Z. Linear-scaling performance is obtained using numerically thresholded sparse matrix algebra based on the ELLPACK-R sparse matrix data format, which also enables efficient shared-memory parallelization. As we show in this article using self-consistent density-functional-based tight binding MD, our approach is faster than conventional methods based on the diagonalization of overlap matrix S for systems as small as a few hundred atoms, substantially accelerating quantum-based simulations even for molecular structures of intermediate size. For a 4158-atom water-solvated polyalanine system, we find an average speedup factor of 122 for the computation of Z in each MD step. PMID- 27267208 TI - "The Wisdom of Age": Perspectives on Aging and Growth among Lesbian Older Adults. AB - Older lesbian-identified women are a health disparate yet resilient population about whom knowledge is limited and emerging. Among the areas in need of research are older lesbians' experiences of later life and stress-related growth. This article presents the findings from a qualitative study that investigated older lesbians' experiences of adversity and adaptation as they age. In-depth, exploratory interviews were conducted with 12 lesbian-identified women who were between the ages of 65-80. This study applied grounded theory methodology to identify respondents sources of stress and fear, their strengths and coping strategies and how those relate to each other and to their growth in later life. We advance a model of adaptive change that shows how spirituality, social support, and resistance to cultural norms help older lesbian adults cope with loss, illness, and discrimination and develop wisdom in later life. Knowledgeable practitioners can help older lesbian women identify and maintain sources of social support, explore spirituality, and facilitate continuous growth through the end of life. Social workers can advocate for services that are welcoming and affirmative so as to reduce fears of isolation and dependence associated with health decline. PMID- 27267209 TI - Clinician as Medical Story Teller. PMID- 27267210 TI - New American Thyroid Association Sonographic Patterns for Thyroid Nodules Perform Well in Medullary Thyroid Carcinoma: Institutional Experience, Systematic Review, and Meta-Analysis. AB - BACKGROUND: The 2015 American Thyroid Association (ATA) thyroid nodule guidelines recommend selecting nodules for biopsy based on a sonographic pattern classification. These patterns were developed based on features of differentiated thyroid cancer. This study aimed to evaluate the performance and the inter observer agreement of this classification system in medullary thyroid carcinoma (MTC). METHODS: The medical records of all patients with MTC evaluated at the authors' institution between 1998 and 2014 were retrospectively reviewed. Only patients with presurgical thyroid ultrasound available for review were included in the study. Five independent reviewers assessed the stored ultrasound images for composition, echogenicity, margins, presence of calcifications, and extrathyroidal extension for each nodule. The presence of suspicious lymph nodes was also evaluated when presurgical lateral neck ultrasound was available for review. Each nodule was classified according to the ATA sonographic patterns. Inter-observer agreement was calculated for each sonographic feature and for the sonographic patterns. To validate the findings, a systematic review of the literature and meta-analysis on the sonographic features of MTC was conducted. RESULTS: In this institutional cohort, the inter-observer agreement for individual sonographic features was moderate to good (kappa = 0.45-0.71), and for the ATA classification it was good (kappa = 0.72). Ninety-seven percent (29/30) of the MTCs were classified in the intermediate or high suspicion patterns. A total of 249 MTCs were included in the meta-analysis. Based on pooled frequencies for solid composition and hypoechogenicity, >95% of MTCs would be classified at least in the intermediate suspicion pattern, warranting the lowest-size threshold for biopsy (>=1 cm). CONCLUSIONS: The sonographic patterns proposed by the ATA perform well in MTC, and inter-observer agreement is good to very good. PMID- 27267211 TI - Immune checkpoint inhibitors as first-line and salvage therapy for advanced non small-cell lung cancer. AB - Advanced non-small-cell lung cancer (NSCLC) has a poor prognosis with few treatment options available for patients after failure of first-line therapy. Nivolumab is the first immune checkpoint inhibitor targeting the PD-1 to be approved in recurrent NSCLC with squamous and nonsquamous histology. More recently, pembrolizumab has also been approved as salvage therapy in PD-L1 positive recurrent NSCLC. The success of immunotherapy in malignant melanoma, previously a disease with no effective treatment, has generated optimism and expectation that some of the checkpoint inhibitors currently in clinical development will soon become available as first-line therapy and hence improve outcomes for the vast majority of patients with advanced NSCLC. This article summarizes the progress accomplished in the field and discusses controversies surrounding the use of immune checkpoint inhibitors. PMID- 27267212 TI - Cognitive-behavioural phenotype in a group of girls from 1.2 to 12 years old with the Incontinentia Pigmenti syndrome: Recommendations for clinical management. AB - Incontinentia Pigmenti (IP, OMIM#308300) is a rare X-linked genomic disorder (about 1,400 cases) that affects the neuroectodermal tissue and Central Nervous System (CNS). The objective of this study was to describe the cognitive behavioural profile in children in order to plan a clinical intervention to improve their quality of life. A total of 14 girls (age range: from 1 year and 2 months to 12 years and 10 months) with IP and the IKBKG/NEMO gene deletion were submitted to a cognitive assessment including intelligence scales, language and visuo-spatial competence tests, learning ability tests, and a behavioural assessment. Five girls had severe to mild intellectual deficiencies and the remaining nine had a normal neurodevelopment. Four girls were of school age and two of these showed no intellectual disability, but had specific disabilities in calculation and arithmetic reasoning. This is the first description of the cognitive-behavioural profile in relation to developmental age. We stress the importance of an early assessment of learning abilities in individuals with IP without intellectual deficiencies to prevent the onset of any such deficit. PMID- 27267213 TI - Bacteriological quality of bottled drinking water versus municipal tap water in Dharan municipality, Nepal. AB - BACKGROUND: Water-related diseases are of great concern in developing countries like Nepal. Every year, there are countless morbidity and mortality due to the consumption of unsafe drinking water. Recently, there have been increased uses of bottled drinking water in an assumption that the bottled water is safer than the tap water and its use will help to protect from water-related diseases. So, the main objective of this study was to analyze the bacteriological quality of bottled drinking water and that of municipal tap water. METHODS: A total of 100 samples (76 tap water and 24 bottled water) were analyzed for bacteriological quality and pH. The methods used were spread plate method for total plate count (TPC) and membrane filter method for total coliform count (TCC), fecal coliform count (FCC), and fecal streptococcal count (FSC). pH meter was used for measuring pH. RESULTS: One hundred percent of the tap water samples and 87.5 % of the bottled water samples were found to be contaminated with heterotrophic bacteria. Of the tap water samples, 55.3 % were positive for total coliforms, compared with 25 % of the bottled water. No bottled water samples were positive for fecal coliforms and fecal streptococci, in contrast to 21.1 % and 14.5 % of the tap water samples being contaminated with fecal coliforms and fecal streptococci, respectively. One hundred percent of the tap water samples and 54.2 % of the bottled water samples had pH in the acceptable range. CONCLUSIONS: All of the municipal tap water samples and most of the bottled drinking water samples distributed in Dharan municipality were found to be contaminated with one or more than one type of indicator organisms. On the basis of our findings, we may conclude that comparatively, the bottled drinking water may have been safer (than tap water) to drink. PMID- 27267214 TI - Pathological findings in a Dachshund-cross dog with neuroaxonal dystrophy. AB - BACKGROUND: Neuroaxonal dystrophy (NAD) is a neurodegenerative condition affecting humans and animals characterized by the widespread presence of swollen axons (spheroids). CASE PRESENTATION: Herein, we report the pathological findings in a case of neuroaxonal dystrophy in a Dachshund-cross puppy, which was euthanized because of a proprioceptive positioning deficits and irreversible ataxia of the hind limbs. Histologically, there was a bilaterally symmetric neuroaxonal dystrophy with eosinophilic axonal spheroids exclusively localized at the level of the ventral posterior lateral nucleus of the thalamus, medial lemniscus, gracilis nucleus, medial cuneatus nucleus in the brain as well as the gracilis and cuneatus fasciculi throughout the spinal cord. CONCLUSION: To the authors' knowledge, this is the first report of canine neuroaxonal dystrophy with this exclusive and specific localization only in the neuronal circuit implicated in the transmission of conscious proprioceptive information. PMID- 27267215 TI - Phenylobacterium aquaticum sp. nov., isolated from the reservoir of a water purifier. AB - A Gram-reaction-negative, strictly aerobic, non-motile, non-spore-forming, rod shaped bacterial strain designated W2-3-4T was isolated from the reservoir of a water purifier. This bacterium was characterized to determine its taxonomic position by using a polyphasic approach. Strain W2-3-4T grew well at 25-30 degrees C on nutrient and R2A agars. On the basis of 16S rRNA gene sequence similarity, strain W2-3-4T was shown to belong to the family Caulobacteraceaeand to be related to Phenylobacterium conjunctumFWC21T (98.0 % sequence similarity) and Phenylobacterium haematophilum CCUG 26751T (97.2 %). Lower sequence similarities were found with the type strains of all other recognized members of the genus Phenylobacterium (95.7-97.1 %). The G+C content of the genomic DNA was 68.7 mol%. The major respiratory quinone was Q-10 and the major fatty acids were summed feature 8 (comprising C18 : 1omega7c and/or C18 : 1omega6c), C16 : 0, C18 : 1omega7c 11-methyl and summed feature 3 (comprising C16 : 1omega7c and/or C16 : 1omega6c). The polar lipids were phosphatidylglycerol, an unknown phospholipid, four unknown glycolipids and three unidentified polar lipids. DNA-DNA relatedness values between strain W2-3-4Tand its closest phylogenetically neighbours were below 7 %. Strain W2-3-4T could be differentiated genotypically and phenotypically from recognized species of the genus Phenylobacterium. The isolate therefore represents a novel species, for which the name Phenylobacterium aquaticum sp. nov. is proposed, with the type strain W2-3-4T (=KACC 18306T=LMG 28593T). PMID- 27267216 TI - Cognitive Behavioural Coaching principles and basic tools to support trainees. PMID- 27267217 TI - Massive Fabrication of Polymer Microdiscs by Phase Separation and Freestanding Process. AB - We present a facile method to fabricate polymer thin films with tens of nanometers thickness and several micrometers size (also called "microdiscs" herein) by applying phase separation of polymer blend. A water-soluble supporting layer is employed to obtain a freestanding microdisc suspension. Owing to their miniaturized size, microdiscs can be injected through a syringe needle. Herein, poly(d,l-lactic acid) microdiscs were fabricated with various thicknesses and sizes, in the range from ca. 10 to 60 nm and from ca. 1.0 to 10.0 MUm, respectively. Magnetic nanoparticles were deposited on polymer microdiscs with a surface coating method. The magnetic manipulation of microdiscs in a liquid environment under an external magnetic field was achieved with controllable velocity by adjusting the microdisc dimensions and the loading amount of magnetic components. Such biocompatible polymer microdiscs are expected to serve as injectable vehicles for targeted drug delivery. PMID- 27267218 TI - A voice from the streets about Spice. PMID- 27267219 TI - Everybody's working for the weekend: changes in enjoyment of everyday activities across the retirement threshold. AB - BACKGROUND: the aim of this study was to explore the associations between use of time and momentary hedonic affect ('enjoyment') in adults in the peri-retirement period. METHODS: a total of 124 adults [61 males, 63 females; age 62 (4) years] completed a computerised use-of-time recall on 4 days at each of four time points (3-6 months pre-, 3, 6 and 12 months post-retirement), as well as surveys regarding self-reported health, well-being, sleep quality and loneliness. They reported how much they enjoyed each activity on a 0-10 scale. An individual Enjoyment Index was calculated as the time-weighted average of each participant's enjoyment ratings. Time-weighted enjoyment ratings were also calculated for nine mutually exclusive and exhaustive activity domains (Sleep, Chores, Work, Social, Screen Time, Self-care, Quiet Time, Transport, Physical Activity) and sub domains. RESULTS: the mean (+/-SD) Enjoyment Index was 7.43 +/- 0.61, and was significantly and positively associated with well-being (P = 0.003 to P < 0.0001) and sleep quality (P = 0.03 to P < 0.0001), and negatively associated with loneliness (P = 0.003 to P < 0.0001). Mean Enjoyment Index values increased significantly (P < 0.0001) from pre-retirement (7.19 +/- 0.82) to post-retirement (7.46 +/- 0.89, 7.42 +/- 0.91 and 7.49 +/- 0.89 at 3, 6 and 12 months post retirement). There were significant differences in enjoyment across domains, with Physical Activity (7.86 +/- 1.11) and Social (7.66 +/- 0.85) being the most enjoyable, and Work (7.10 +/- 0.89) and Chores (7.09 +/- 0.85) the least enjoyable. CONCLUSION: enjoyment of everyday activities increased after retirement and remained elevated for at least 12 months. Work appears to constitute a relative hedonic deficit. PMID- 27267220 TI - Initial manifestation of type I diabetes mellitus as an unusual cause of early post-operative seizures. AB - We present a case of an 18-year-old patient who underwent resective epilepsy surgery for intractable epilepsy caused by focal cortical dysplasia. In the early post-surgical period, the patient started experiencing atypical seizures refractory to antiepileptic treatment. In due course, abnormally low levels of blood sodium and extremely high levels of blood glucose were discovered. Significant hyperglycaemia was initially ascribed to steroid-induced diabetes, and antibodies specific to type I diabetes mellitus were subsequently detected, confirming the diagnosis. Following stabilization of glucose and electrolyte levels, the patient became seizure-free. To our knowledge, this is the first report of presentation of type I diabetes as the cause of early post-operative seizures. We discuss less common aetiologies of seizures in the early post operative period, including metabolic disturbances. Based on our experience, we stress the importance of electrolyte and glucose monitoring in the setting of acute post-operative seizures. PMID- 27267221 TI - Surfactant-Triggered Nanoarchitectonics of Fullerene C60 Crystals at a Liquid Liquid Interface. AB - Here, we report the structural and morphological modulation of fullerene C60 crystals induced by nonionic surfactants diglycerol monolaurate (C12G2) and monomyristate (C14G2). C60 crystals synthesized at a liquid-liquid interface comprising isopropyl alcohol (IPA) and a saturated solution of C60 in ethylbenzene (EB) exhibited a one-dimensional (1D) morphology with well-defined faceted structure. Average length and diameter of the faceted rods were ca. 4.8 MUm and 747 nm, respectively. Powder X-ray diffraction pattern (pXRD) confirmed a hexagonal-close packed (hcp) structure with cell dimensions ca. a = 2.394 nm and c = 1.388 nm. The 1D rod morphology of C60 crystals was transformed into "Konpeito candy-like" crystals (average diameter ca. 1.2 MUm) when the C60 crystals were grown in the presence of C12G2 or C14G2 surfactant (1%) in EB. The pXRD spectra of "Konpeito-like" crystals could be assigned to the face-centered cubic (fcc) phase with cell dimensions ca. a = 1.4309 nm (for C12G2) and a = 1.4318 nm (for C14G2). However, clusters or aggregates of C60 lacking a uniform morphology were observed at lower surfactant concentrations (0.1%), although these crystals exhibited an fcc crystal structure. The self-assembled 1D faceted C60 crystals and "Konpeito-like" C60 crystals exhibited intense photoluminescence (PL) (~35 times greater than pC60) and a blue-shifted PL intensity maximum (~15 nm) compared to those of pC60, demonstrating the potential use of this method for the control of the optoelectronic properties of fullerene nanostructures. The "Konpeito-like" crystals were transformed into high surface area nanoporous carbon with a graphitic microstructure upon heat-treatment at 2000 degrees C. The heat-treated samples showed enhanced electrochemical supercapacitance performance (specific capacitance is ca. 175 F g-1, which is about 20 times greater than pC60) with long cyclic stability demonstrating the potential of the materials in supercapacitor device fabrication. PMID- 27267222 TI - Hour glass half full or half empty? Future time perspective and preoccupation with negative events across the life span. AB - According to socioemotional selectivity theory, older adults' emotional well being stems from having a limited future time perspective that motivates them to maximize well-being in the "here and now." Presumably, then, older adults' time horizons are associated with emotional competencies that boost positive affect and dampen negative affect, but little research has addressed this. Using a U.S. adult life-span sample (N = 3,933; 18-93 years), we found that a 2-factor model of future time perspective (future opportunities; limited time) fit the data better than a 1-factor model. Through middle age, people perceived the life-span hourglass as half full-they focused more on future opportunities than limited time. Around Age 60, the balance changed to increasingly perceiving the life-span hourglass as half empty-they focused less on future opportunities and more on limited time, even after accounting for perceived health, self-reported decision making ability, and retirement status. At all ages, women's time horizons focused more on future opportunities compared with men's, and men's focused more on limited time. Focusing on future opportunities was associated with reporting less preoccupation with negative events, whereas focusing on limited time was associated with reporting more preoccupation. Older adults reported less preoccupation with negative events, and this association was stronger after controlling for their perceptions of limited time and fewer future opportunities, suggesting that other pathways may explain older adults' reports of their ability to disengage from negative events. Insights gained and questions raised by measuring future time perspective as 2 dimensions are discussed. (PsycINFO Database Record PMID- 27267224 TI - Malnourishment and length of hospital stay among paediatric cancer patients with febrile neutropaenia: a developing country perspective. AB - OBJECTIVES: The prevalence of malnourishment among paediatric cancer patients undergoing chemotherapy in developing countries is poorly documented despite greater potential for malnourishment in such settings. We aimed to estimate the prevalence of malnourishment among paediatric cancer patients in Mexico City, and assess the association between malnourishment and length of hospital stay. METHODS: Individuals eligible for this study were paediatric cancer patients (aged <18 years) admitted to Hospital Infantil de Mexico Federico Gomez (Mexico City) with febrile neutropaenia. Our exposure of interest, malnourishment, was defined as an age-adjusted and sex-adjusted z-score<-2 (ie, 2 SDs below the expected mean of the WHO reference population). We estimated time ratios (TRs) and 95% confidence limits (CLs) for the association between malnourishment and length of hospital stay. RESULTS: Our study population comprised 111 paediatric cancer patients with febrile neutropaenia, of whom 71% were aged <10 years and 52% were males. The prevalence of malnourishment was 14%, equal to a 530% (standardised morbidity ratio=6.3; 95% CL 3.7, 10) excess of malnourishment compared with the world reference population. The median length of hospital stay for malnourished patients was 15 days, which corresponded with a 50% (TR=1.5, 95% CL 1.0, 2.3) relative increase in length of stay compared with patients who were not malnourished. Patients with body mass indices equal to the mean of the world reference population had the shortest length of stay. CONCLUSIONS: Future studies should explore potential interventions for malnourishment to reduce the length of hospital stay or other established adverse consequences of malnourishment. PMID- 27267225 TI - Comment on Montenigro et al., "Cumulative Head Impact Exposure Predicts Later Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players". PMID- 27267223 TI - Life-table studies revealed significant effects of deforestation on the development and survivorship of Anopheles minimus larvae. AB - BACKGROUND: Many developing countries are experiencing rapid ecological changes such as deforestation and shifting agricultural practices. These environmental changes may have an important consequence on malaria due to their impact on vector survival and reproduction. Despite intensive deforestation and malaria transmission in the China-Myanmar border area, the impact of deforestation on malaria vectors in the border area is unknown. METHODS: We conducted life table studies on Anopheles minimus larvae to determine the pupation rate and development time in microcosms under deforested, banana plantation, and forested environments. RESULTS: The pupation rate of An. minimus was 3.8 % in the forested environment. It was significantly increased to 12.5 % in banana plantations and to 52.5 % in the deforested area. Deforestation reduced larval-to-pupal development time by 1.9-3.3 days. Food supplementation to aquatic habitats in forested environments and banana plantations significantly increased larval survival rate to a similar level as in the deforested environment. CONCLUSION: Deforestation enhanced the survival and development of An. minimus larvae, a major malaria vector in the China-Myanmar border area. Experimental determination of the life table parameters on mosquito larvae under a variety of environmental conditions is valuable to model malaria transmission dynamics and impact by climate and environmental changes. PMID- 27267226 TI - A corpus of potentially contradictory research claims from cardiovascular research abstracts. AB - BACKGROUND: Research literature in biomedicine and related fields contains a huge number of claims, such as the effectiveness of treatments. These claims are not always consistent and may even contradict each other. Being able to identify contradictory claims is important for those who rely on the biomedical literature. Automated methods to identify and resolve them are required to cope with the amount of information available. However, research in this area has been hampered by a lack of suitable resources. We describe a methodology to develop a corpus which addresses this gap by providing examples of potentially contradictory claims and demonstrate how it can be applied to identify these claims from Medline abstracts related to the topic of cardiovascular disease. METHODS: A set of systematic reviews concerned with four topics in cardiovascular disease were identified from Medline and analysed to determine whether the abstracts they reviewed contained contradictory research claims. For each review, annotators were asked to analyse these abstracts to identify claims within them that answered the question addressed in the review. The annotators were also asked to indicate how the claim related to that question and the type of the claim. RESULTS: A total of 259 abstracts associated with 24 systematic reviews were used to form the corpus. Agreement between the annotators was high, suggesting that the information they provided is reliable. CONCLUSIONS: The paper describes a methodology for constructing a corpus containing contradictory research claims from the biomedical literature. The corpus is made available to enable further research into this area and support the development of automated approaches to contradiction identification. PMID- 27267227 TI - Comparative Analysis of Radiographic Hip Joint Geometry Using Measurement Tools on Picture Archiving and Communication System: A Prospective Study of 100 Pelvic Radiographs of Koreans. AB - BACKGROUND: A contralateral normal hip joint has been often used as a reference standard in preoperative planning and intraoperative assessment of hip arthroplasty, with the assumption that bilateral hip joint geometries have no significant differences. However, one previous study using analog measurements on hardcopy films reported significant bilateral variation in hip joint geometry. We therefore investigated the level of agreement between the right and left hips for each measurement and determined index values and the range of normal bilateral variations. METHODS: We assessed 100 standard anteroposterior radiographs of the pelvis in this study. Two independent observers measured the actual value of femoral head diameter, location of the femoral head center, acetabular offset, femoral offset, hip offset, greater trochanteric height, neck-shaft angle, medullary canal diameter, and proximal femoral diameter. Intraclass correlation coefficients (ICCs) and values of mean difference were calculated for each measurement. RESULTS: The results demonstrated perfect agreement (ICC >0.8) between the right and left hips for most parameters and substantial agreement for greater trochanteric height (ICC = 0.735) and femoral offset (ICC = 0.773). The mean difference and standard deviation in the measurement between the right and left hips for the location of the femoral head center and the acetabular offset were 0.60 +/- 0.48 mm and 0.42 +/- 0.30 mm, respectively. CONCLUSION: Hip joint geometry is not influenced by side. In hip arthroplasty, a contralateral normal hip can be reliably used as a guide for preoperative planning using measurement tools on a picture archiving and communication system. PMID- 27267228 TI - Intravenous vs Topical Tranexamic Acid in Total Knee Arthroplasty Without Tourniquet Application: A Randomized Controlled Study. AB - BACKGROUND: Use of tranexamic acid (TXA) is effective and safe in reducing the blood loss in total knee arthroplasty (TKR) performed using a tourniquet, but, data in TKR performed without tourniquet are limited, and there is no study comparing the topical (T) with intravenous (IV) TXA administration. Our aim was to compare the topical (T) with intravenous (IV) TXA administration in TKR performed without tourniquet. MATERIAL AND METHODS: A total of 120 patients undergoing unilateral TKR for knee osteoarthritis were included in a prospective randomized study. Operations were performed under spinal anesthesia, no tourniquet was used, and the postoperative regime was the same for all patients. Patients were divided into 3 groups; in group C (control), 40 patients received no TXA, in group IV, 40 patients received 1 g of TXA intravenously, and in group L, 1 g of TXA was applied locally to 40 patients. The primary outcome measures included the calculated blood loss, the transfusion rate, and quantity of allogeneic blood units, whereas secondary outcome measures were complications. RESULTS: There was no statistically significant difference in patient's demographics and perioperative results. Calculated blood loss, allogeneic blood transfusion rate, and quantity in group C were significantly higher compared with those of TXA groups (P < .001). There was no significant difference in complications rate between the 3 groups. CONCLUSIONS: According to the results of this study, IV or T administration of 1-g TXA significantly reduced the blood loss and the need for allogeneic blood transfusion in patients undergoing TKR without a tourniquet (with no significant difference between the 2 routes of administration). PMID- 27267229 TI - The Distance of the Common Peroneal Nerve to the Posterolateral Structures of the Knee. AB - BACKGROUND: The common peroneal nerve (CPN) is an important structure of the lower limb and is at risk of injury during total knee arthroplasty. The aim of this study was to use a tibial reference system to determine the position of the CPN relative to the knee center and popliteus. METHODS: Two hundred consecutive knee magnetic resonance images at the level of a standard tibial arthroplasty cut were evaluated for (1) distance of the CPN from the posterolateral capsule; (2) angle of the CPN from the center of the tibial anteroposterior axis; and (3) location of CPN with respect to the popliteus. RESULTS: The mean distance between the CPN and the posterolateral joint capsule was 11.9 mm (range, 4.7-22.13 mm), which correlated positively with the medial-lateral axis of the tibia (Pearson correlation, 0.157; P = .026) and negatively with the angle of the nerve from the midline (Pearson correlation, -0.237, P = .001). The mean angle of the nerve from the midline was 42.2 degrees (range, 25.0 degrees -64.0 degrees ). In 116 knees (58%), the CPN was in line with the popliteus from the center of the knee, in 69 knees (34.5%) the CPN was lateral to the popliteus, and in 15 knees (7.5%), the CPN was medial to the popliteus. A danger zone was identified as between 29.95 degrees and 54.57 degrees from the anteroposterior axis. CONCLUSION: The CPN is at risk during total knee arthroplasty. This study describes a method to help predict the location of the CPN intraoperatively and therefore avoid direct injury. PMID- 27267231 TI - Hearing-related quality of life outcomes for Singaporean children using hearing aids or cochlear implants. AB - OBJECTIVES: The Children Using Hearing Devices Quality of Life Questionnaire (CuHDQOL) is a new parent-administered hearing-specific questionnaire for children fitted with hearing devices. The aim of this study was to assess outcomes for hearing-impaired children in Singapore using this measure, as well as to examine its applicability for use in a clinical setting. MATERIALS AND METHODS: The CuHDQOL has 26 items, uses a recall period of 1 month, and is divided into three sections: parental perspectives and expectations (eight items), impact on the family (eight items) and hearing-related quality of life (QOL) of the child (10 items). Responses are made on a 5-point Likert scale, and transformed to a score from 0-100. Twenty-two parents of children with hearing aids and 14 parents of children with cochlear implants completed the CuHDQOL. RESULTS: The mean total CuHDQOL scores was 62/100 for the children using hearing aids and 53/100 for children with cochlear implants. Scores for the children using hearing aids were higher across all subscales, with a linear regression showing this to be significant for the parental perspectives and expectations subscale (B=-10.58, P=0.041). Analyses of Variance showed that both the 'Parent Perspective and Expectations' and the 'Hearing-related QOL' subscales were significantly higher than the 'Impact on Family' subscale for both groups (P<=0.003). CONCLUSIONS: The CuHDQOL was found to be a simple, efficient questionnaire that could easily be incorporated into clinical practice to provide a more holistic evaluation of a child's outcomes post intervention, and/or to monitor their progress over time. PMID- 27267230 TI - Risk Factors for Wound Complications After Direct Anterior Approach Hip Arthroplasty. AB - BACKGROUND: Previous studies have suggested that wound complications may be higher after direct anterior approach (DAA) hip arthroplasty, but, specific risk factors have not been closely examined. METHODS: We conducted a retrospective case-control study of 651 consecutive DAA hip arthroplasty surgeries performed by 2 surgeons over a 3-year period. Outcome measures included any postoperative wound problem (including prolonged drainage, wound dehiscence, wound necrosis, suture granuloma, and superficial infection) requiring additional intervention or reoperation. Univariate odds ratios (ORs) were calculated, and multivariate logistic regression analysis was performed to determine risk correlation. Receiver operator characteristic (ROC) curves were created to determine disease predictability. RESULTS: A total of 75 patients (11.5%) experienced wound complications requiring additional intervention, of which, 13 (1.9%) required reoperation. Multivariate regression analysis found that development of wound complications was significantly and independently associated with body mass index (BMI) 30-35 kg/m2 (OR 2.05; 95% confidence interval [CI] 1.08-3.88), BMI 35-40 kg/m2 (OR 3.40; 95% CI 1.42-8.26), BMI > 40 kg/m2 (OR 7.28; 95% CI 2.55-20.78), and diabetes mellitus (OR 2.97; 95% CI 1.46-6.07). Reoperation for wound complication was significantly associated with BMI > 40 kg/m2 (OR 5.68; 95% CI 1.17-27.48) and diabetes mellitus (OR 13.08; 95% CI 3.97-43.11). Optimal cutoff values for BMI were found through receiver operator characteristic curve analysis to be 28.0 kg/m2 for development of wound complications and 28.2 kg/m2 for reoperation for wound complications. CONCLUSION: Obesity and diabetes mellitus are significantly associated with postoperative wound-healing complications and the need for reoperation for these wound complications after DAA hip arthroplasty. PMID- 27267233 TI - Prolonged and intensive medication use are associated with the obesity paradox after percutaneous coronary intervention: a systematic review and meta-analysis of 12 studies. AB - BACKGROUND: Obesity paradox is defined as the unexpected decrease in the total number of death which has been observed among patients who are overweight and obese compared to patients with normal weight after undergoing revascularization by percutaneous coronary intervention (PCI). Despite of so many recent studies which showed the existence of this phenomenon, prolonged and intensive medication use were only suggested to be among the reasons responsible for this 'obesity paradox' but it was never confirmed whether this hypothesis should really be considered true or not. Therefore, this study aimed to investigate whether prolonged and intensive medication use were associated with this obesity paradox after PCI. METHODS: Medline, PubMed, EMBASE and the Cochrane Library were searched for studies showing the existence of this 'obesity paradox' in patients who underwent coronary revascularization by PCI and only articles comprising of medication use among the patients analyzed were considered relevant for this research. Medication use among the different subgroups of patients was calculated. Mortality was considered as the clinical endpoint in this study. Risk Ratio (RR) with 95 % Confidence Interval (CI) was used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. RESULTS: Twelve studies consisting of a total number of 91,582 patients was included in this meta-analysis. An intensive medication use after the hospital discharge and during the follow up period after PCI was observed in the subgroup of obese patients, followed by the overweight patients and the normal weight patients respectively. Our results showed that the short-term (30 days) mortality in overweight and obese patients was significantly lower compared to the normal weight patients with RR: 0.72; 95 % CI: 0.56-0.92, p = 0.008 and RR: 0.47, 95 % CI: 0.34-0.65; p < 0.00001 respectively. The long-term (>= one year) mortality was also significantly lower in the overweight and the obese groups with RR: 0.74, 95 % CI: 0.67-0.82; p < 0.00001 and RR: 0.63, 95 % CI: 0.55 0.72; p < 0.00001 respectively. CONCLUSION: Our study has confirmed to some extent, that prolonged and intensive use of medications which were more prominent in patients who were overweight and obese during the follow up period, might apparently be among the reasons responsible for this obesity paradox after PCI. PMID- 27267232 TI - Lanthipeptides: chemical synthesis versus in vivo biosynthesis as tools for pharmaceutical production. AB - Lanthipeptides (also called lantibiotics for those with antibacterial activities) are ribosomally synthesized post-translationally modified peptides having thioether cross-linked amino acids, lanthionines, as a structural element. Lanthipeptides have conceivable potentials to be used as therapeutics, however, the lack of stable, high-yield, well-characterized processes for their sustainable production limit their availability for clinical studies and further pharmaceutical commercialization. Though many reviews have discussed the various techniques that are currently employed to produce lanthipeptides, a direct comparison between these methods to assess industrial applicability has not yet been described. In this review we provide a synoptic comparison of research efforts on total synthesis and in vivo biosynthesis aimed at fostering lanthipeptides production. We further examine current applications and propose measures to enhance product yields. Owing to their elaborate chemical structures, chemical synthesis of these biomolecules is economically less feasible for large scale applications, and hence biological production seems to be the only realistic alternative. PMID- 27267235 TI - A Sketch of the Taiwan Zebrafish Core Facility. AB - In the past three decades, the number of zebrafish laboratories has significantly increased in Taiwan. The Taiwan Zebrafish Core Facility (TZCF), a government funded core facility, was launched to serve this growing community. The Core Facility was built on two sites, one located at the National Health Research Institutes (NHRI, called Taiwan Zebrafish Core Facility at NHRI or TZeNH) and the other is located at the Academia Sinica (Taiwan Zebrafish Core Facility at AS a.k.a. TZCAS). The total surface area of the TZCF is about 180 m(2) encompassing 2880 fish tanks. Each site has a separate quarantine room and centralized water recirculating systems, monitoring key water parameters. To prevent diseases, three main strategies have been implemented: (1) imported fish must be quarantined; (2) only bleached embryos are introduced into the main facilities; and (3) working practices were implemented to minimize pathogen transfer between stocks and facilities. Currently, there is no health program in place; however, a fourth measure for the health program, specific regular pathogen tests, is being planned. In March 2015, the TZCF at NHRI has been AAALAC accredited. It is our goal to ensure that we provide "disease-free" fish and embryos to the Taiwanese research community. PMID- 27267234 TI - Maternal and perinatal conditions and the risk of developing celiac disease during childhood. AB - BACKGROUND: Celiac disease (CD) is increasing worldwide, which might be due to the changing environmental and lifestyle exposures. We aimed to explore how conditions related to maternity, delivery and the neonatal period influence CD onset during childhood. METHODS: Using Sweden's national registers we had access to information on 1 912 204 children born between 1991 and 2009, 6 596 of whom developed CD before 15 years of age. Logistic regression analyses were performed to determine how CD is associated with maternity, delivery and the neonatal period. RESULTS: Regardless of sex, a reduction in CD risk was observed in children born to mothers aged >=35 years (odds ratio [OR] 0.8; 95 % confidence interval [CI] 0.7-0.9) and with high maternal income (OR 0.9; 95 % CI 0.8-0.9). Being a second-born child, however, was positively associated with CD. Among boys, elective caesarean delivery increased the risk of CD (OR 1.2; 95 % CI 1.0 1.4), while maternal overweight (OR 0.9; 95 % CI 0.8-0.9), premature rupture of the membrane (OR 0.4; 95 % CI 0.2-0.8) and low birth weight showed a negative association. Girls had an increased CD risk compared to boys and in girls the risk was increased by repeated maternal urinary tract infections (OR 1.1; 95 % CI 1.0-1.2). CONCLUSIONS: Elective caesarean delivery and repeated maternal urinary tract infections during pregnancy are associated with increased risk of CD onset during childhood, suggesting the role of dysbiosis during early life. High maternal age and high income reduced the risk of CD, which might be due to infant feeding practices and life style. PMID- 27267242 TI - Korean nurses' perspectives regarding handoffs. AB - BACKGROUND: Nursing handoffs are communicative routines in most nursing units. The handoff is critical to the continuity and safety of patient care. Negative perceptions of handoffs could hinder efficient communication between nurses. AIMS: This study identified the perceptions of nurses' handoffs in Korea. DESIGN: A descriptive survey was employed. The population included nurses who worked in a general ward in 201 hospitals with more than 300 beds. RESULTS: 27.9% responded that the current handoff method needed to be changed and 75.8% had no handoff related guideline. "Handoffs are frequently interrupted by outsiders' visits" was the most frequent problem expressed. Variables associated with a perceived need for change in handoff methods were age, handoff method, and preparation time for handoffs. CONCLUSION: Nurses recognized that handoffs were frequently interrupted by external factors and consumed too much time. Therefore, a standardized handoff method is needed to ensure the accuracy of information. PMID- 27267243 TI - Variation in left posterior parietal-motor cortex interhemispheric facilitation following right parietal continuous theta-burst stimulation in healthy adults. AB - Spatial neglect is modeled on an imbalance of interhemispheric inhibition (IHI); however evidence is emerging that it may not explain neglect in all cases. The aim of this study was to investigate the IHI imbalance model of visual neglect in healthy adults, using paired pulse transcranial magnetic stimulation to probe excitability of projections from posterior parietal cortex (PPC) to contralateral primary motor cortex (M1) bilaterally. Motor-evoked potentials (MEPs) were recorded from the first dorsal interossei and facilitation was determined as ratio of conditioned to non-conditioned MEP amplitude. A laterality index reflecting the balance of excitability between the two hemispheres was calculated. A temporal order judgment task (TOJ) assessed visual attention. Continuous theta-burst stimulation was used to transiently suppress right parietal cortex activity and the effect on laterality and judgment task measured, along with associations between baseline and post stimulation measures. Stimulation had conflicting results on laterality, with most participants demonstrating an effect in the negative direction with no decrement in the TOJ task. Correlation analysis suggests a strong association between laterality direction and degree of facilitation of left PPC-to right M1 following stimulation (r=.902), with larger MEP facilitation at baseline demonstrating greater reduction (r=-.908). Findings indicate there was relative balance between the cortices at baseline but right PPC suppression did not evoke left PPC facilitation in most participants, contrary to the IHI imbalance model. Left M1 facilitation prior to stimulation may predict an individual's response to continuous theta-burst stimulation of right PPC. PMID- 27267244 TI - The high-frequency component of heart rate variability during extended wakefulness is closely associated with the depth of the ensuing sleep in C57BL6 mice. AB - This study aimed to test the hypothesis that, during extended wakefulness, parasympathetic activity is associated with the depth of the subsequent recovery sleep in mice. Fourteen male C57BL/6 mice were implanted with electrodes for sleep recording. Continuous spectral analysis was performed on the electroencephalogram (EEG) to obtain theta power (6-9Hz) and delta power (0-4Hz), as well as the R-R interval signals in order to quantify the high-frequency power (HF) and normalized low-frequency power (LF%) that are used to assess parasympathetic and sympathetic activity, respectively. All animals underwent a sleep deprivation experiment and a control experiment (6-h intervention and 1-h recovery period) on two separate days. During sleep deprivation, HF and theta power during wakefulness were significantly higher than during the control wakefulness after the second hour and first hour, respectively. During recovery non-rapid eye movement sleep, there was a rebound in sleep time and delta power as well as an elevation in HF relative to control post-intervention sleep. Both the rise in HF and theta power during extended wakefulness were found to be positively correlated with the delta power rebound. Furthermore, the HF change during extended wakefulness was also correlated with the amount of sleep loss and the enhancement of waking theta power. Our finding suggests that waking parasympathetic activity intimately reflects the cumulative sleep pressure, suggesting a potential role to be an autonomic marker for sleep propensity. PMID- 27267247 TI - Noradrenergic Locus Coeruleus pathways in pain modulation. AB - The noradrenergic system is crucial for several activities in the body, including the modulation of pain. As the major producer of noradrenaline (NA) in the central nervous system (CNS), the Locus Coeruleus (LC) is a nucleus that has been studied in several pain conditions, mostly due to its strategic location. Indeed, apart from a well-known descending LC-spinal pathway that is important for pain control, an ascending pathway passing through this nucleus may be responsible for the noradrenergic inputs to higher centers of the pain processing, such as the limbic system and frontal cortices. Thus, the noradrenergic system appears to modulate different components of the pain experience and accordingly, its manipulation has distinct behavioral outcomes. The main goal of this review is to bring together the data available regarding the noradrenergic system in relation to pain, particularly focusing on the ascending and descending LC projections in different conditions. How such findings influence our understanding of these conditions is also discussed. PMID- 27267246 TI - AMP kinase regulates ligand-gated K-ATP channels in substantia nigra dopamine neurons. AB - AMP-activated protein kinase (AMPK) is a master enzyme that regulates ATP sensitive K(+) (K-ATP) channels in pancreatic beta-cells and cardiac myocytes. We used patch pipettes to record currents and potentials to investigate effects of AMPK on K-ATP currents in substantia nigra compacta (SNC) dopamine neurons in slices of rat midbrain. When slices were superfused repeatedly with the K-ATP channel opener diazoxide, we were surprised to find that diazoxide currents gradually increased in magnitude, reaching 300% of the control value 60min after starting whole-cell recording. However, diazoxide current increased significantly more, to 472% of control, when recorded in the presence of the AMPK activator A769662. Moreover, superfusing the slice with the AMPK blocking agent dorsomorphin significantly reduced diazoxide current to 38% of control. Control experiments showed that outward currents evoked by the K-ATP channel opener NN 414 also increased over time, but not currents evoked by the GABAB agonist baclofen. Delaying the application of diazoxide after starting whole-cell recording correlated with augmentation of current. Loose-patch recording showed that diazoxide produced a 34% slowing of spontaneous firing rate that did not intensify with repeated applications of diazoxide. However, superfusion with A769662 significantly augmented the inhibitory effect of diazoxide on firing rate. We conclude that K-ATP channel function is augmented by AMPK, which is activated during the process of making whole-cell recordings. Our results suggest that AMPK and K-ATP interactions may play an important role in regulating dopamine neuronal excitability. PMID- 27267248 TI - Characterization of TistH, a multifunctional peptide from the scorpion Tityus stigmurus: Structure, cytotoxicity and antimicrobial activity. AB - The presence of bioactive peptides in animal venoms has been targeted in scientific research for assessing biological activities, as well as mechanisms of action. A recent study by our group observed hypotensive action of TistH (Tityus stigmurus Hypotensin), a peptide deduced from the transcriptome of T. stigmurus venom gland. The present study aims to analyze TistH structure properties and to evaluate its toxicity on normal and tumor cells, its in vitro antimicrobial activity, as well as its inflammatory effect. Circular dichroism analyses of TistH showed a general predominance of alpha-helix conformation in TFE (20-70%) and structural stability to pH variations. TistH was not cytotoxic to normal cell lines (3T3, RAW and HEK), and also not to cancer cell lines (HeLa, B16, 786-0, SiHa and HepG2). The peptide did not present inflammatory activity up to 6 h after administered subcutaneously to Swiss mice. It was observed that concentrations of 4-1024 MUg/mL of TistH produced no inhibition against the bacteria Staphylococcus aureus, Staphylococcus epidermidis e Pseudomonas aeruginosa. The results of antifungal assays showed a moderate activity of TistH against Candida albicans strain LM-108 and the filamentous fungus Trichophyton rubrum LM-640, with growth inhibition at a concentration of 1024 MUg/mL. In contrast, the peptide presented a greater activity (MIC 128 MUg/mL) against C. albicans LM-106, Candida tropicalis ATCC 13308 and Aspergillus flavus strains LM 247 and LM-26, fungi that cause oral and vaginal infections, candidiasis and respiratory allergies, respectively. The present data contribute to a better understanding of TistH and its possible use as a bioactive compound. This multifunctional peptide is capable of acting as anti-hypertensive, as well as to inhibit the growth of fungal strains, having low toxicity, which suggests its safety for using as a pharmacological agent. PMID- 27267245 TI - Cognitive flexibility impairment and reduced frontal cortex BDNF expression in the ouabain model of mania. AB - Central infusion of the Na+/K+-ATPase inhibitor, ouabain in rats serves as an animal model of mania because it leads to hyperactivity, as well as reproduces ion dysregulation and reduced brain-derived neurotrophic factor (BDNF) levels similar to that observed in bipolar disorder. Bipolar disorder is also associated with cognitive inflexibility and working memory deficits. It is unknown whether ouabain treatment in rats leads to similar cognitive flexibility and working memory deficits. The present study examined the effects of an intracerebral ventricular infusion of ouabain in rats on spontaneous alternation, probabilistic reversal learning and BDNF expression levels in the frontal cortex. Ouabain treatment significantly increased locomotor activity, but did not affect alternation performance in a Y-maze. Ouabain treatment selectively impaired reversal learning in a spatial discrimination task using an 80/20 probabilistic reinforcement procedure. The reversal learning deficit in ouabain-treated rats resulted from an impaired ability to maintain a new choice pattern (increased regressive errors). Ouabain treatment also decreased sensitivity to negative feedback during the initial phase of reversal learning. Expression of BDNF mRNA and protein levels was downregulated in the frontal cortex which also negatively correlated with regressive errors. These findings suggest that the ouabain model of mania may be useful in understanding the neuropathophysiology that contributes to cognitive flexibility deficits and test potential treatments to alleviate cognitive deficits in bipolar disorder. PMID- 27267249 TI - Brain regions involved in subprocesses of small-space episodic object-location memory: a systematic review of lesion and functional neuroimaging studies. AB - Object-location memory (OLM) enables us to keep track of the locations of objects in our environment. The neurocognitive model of OLM (Postma, A., Kessels, R. P. C., & Van Asselen, M. (2004). The neuropsychology of object-location memory. In G. L. Allen (Ed.), Human spatial memory: Remembering where (pp. 143-160). Mahwah, NJ: Lawrence Erlbaum, Postma, A., Kessels, R. P. C., & Van Asselen, M. (2008). How the brain remembers and forgets where things are: The neurocognition of object-location memory. Neuroscience & Biobehavioral Reviews, 32, 1339-1345. doi: 10.1016/j.neubiorev.2008.05.001 ) proposes that distinct brain regions are specialised for different subprocesses of OLM (object processing, location processing, and object-location binding; categorical and coordinate OLM; egocentric and allocentric OLM). It was based mainly on findings from lesion studies. However, recent episodic memory studies point to a contribution of additional or different brain regions to object and location processing within episodic OLM. To evaluate and update the neurocognitive model of OLM, we therefore conducted a systematic literature search for lesion as well as functional neuroimaging studies contrasting small-space episodic OLM with object memory or location memory. We identified 10 relevant lesion studies and 8 relevant functional neuroimaging studies. We could confirm some of the proposals of the neurocognitive model of OLM, but also differing hypotheses from episodic memory research, about which brain regions are involved in the different subprocesses of small-space episodic OLM. In addition, we were able to identify new brain regions as well as important research gaps. PMID- 27267250 TI - Estimating the prevalence of female genital mutilation in Portugal. AB - OBJECTIVES: Due to globalized migratory processes, female genital mutilation/cutting (FGM/C) has spread to other countries, including countries in Europe, where, with a few exceptions, it remains a concealed problem. To the authors' knowledge, this is the first national extensive study to estimate the prevalence of FGM/C in Portugal. STUDY DESIGN: Prevalence estimation. METHODS: Using extrapolation of country-of-origin prevalence data and the 2011 Census data, this study estimated: the prevalence of FGM/C in Portugal among women of reproductive age (15-49 years) and among all women aged >=15 years; and the number of girls aged <15 years living in Portugal who have undergone or will probably undergo FGM/C. RESULTS: It is estimated that 6576 women aged >=15 years living in Portugal have undergone FGM/C, with cases distributed unevenly throughout the national territory. In addition, it is estimated that 1830 girls aged <15 years living in Portugal have undergone or are likely to undergo FGM/C. CONCLUSIONS: This study estimated that more than 6000 women living in Portugal have undergone FGM/C, and many girls remain at risk. These two groups need different types of interventions. Awareness of the number and geographical dispersion of cases of FGM/C will enable more informed and targeted definition of public health policies for protection of females who have undergone or are at risk of undergoing FGM/C. PMID- 27267251 TI - The Associations Between Children's and Adolescents' Suicidal and Self-Harming Behaviors, and Related Behaviors Within Their Social Networks: A Systematic Review. AB - Social influences-including the suicidal and self-harming behaviors of others have been highlighted as a risk factor for suicidal and self-harming behavior in young people, but synthesis of the evidence is lacking. A systematic review of 86 relevant papers was conducted. Considerable published evidence was obtained for positive associations between young people's suicidal and self-harming behavior and that of people they know, with those reporting knowing people who had engaged in suicidal or self-harming behaviors more likely to report engaging in similar behaviors themselves. Findings are discussed in relation to a number of methodological and measurement issues-including the role of normative perceptions and implications for the prevention of suicidal and self-harming behavior are considered. PMID- 27267253 TI - Composition and metabolism of phospholipids in Octopus vulgaris and Sepia officinalis hatchlings. AB - The objective of the present study was to characterise the fatty acid (FA) profiles of the major phospholipids, of Octopus vulgaris and Sepia officinalis hatchlings, namely phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylinositol (PI) and phosphatidylethanolamine (PE); and to evaluate the capability of both cephalopod species on dietary phospholipid remodelling. Thus, O. vulgaris and S. officinalis hatchlings were in vivo incubated with 0.3MUM of L ?-1-palmitoyl-2-[1-(14)C]arachidonyl-PC or L-?-1-palmitoyl-2-[1-(14)C]arachidonyl PE. Octopus and cuttlefish hatchlings phospholipids showed a characteristic FA profiles with PC presenting high contents of 16:0 and 22:6n-3 (DHA); PS having high 18:0, DHA and 20:5n-3 (EPA); PI a high content of saturated FA; and PE showing high contents of DHA and EPA. Interestingly, the highest content of 20:4n 6 (ARA) was found in PE rather than PI. Irrespective of the phospholipid in which [1-(14)C]ARA was initially bound (either PC or PE), the esterification pattern of [1-(14)C]ARA in octopus lipids was similar to that found in their tissues with high esterification of this FA into PE. In contrast, in cuttlefish hatchlings [1 (14)C]ARA was mainly recovered in the same phospholipid that was provided. These results showed a characteristic FA profiles in the major phospholipids of the two species, as well as a contrasting capability to remodel dietary phospholipids, which may suggest a difference in phospholipase activities. PMID- 27267252 TI - N-Myristoyltransferase Inhibition Induces ER-Stress, Cell Cycle Arrest, and Apoptosis in Cancer Cells. AB - N-Myristoyltransferase (NMT) covalently attaches a C14 fatty acid to the N terminal glycine of proteins and has been proposed as a therapeutic target in cancer. We have recently shown that selective NMT inhibition leads to dose responsive loss of N-myristoylation on more than 100 protein targets in cells, and cytotoxicity in cancer cells. N-myristoylation lies upstream of multiple pro proliferative and oncogenic pathways, but to date the complex substrate specificity of NMT has limited determination of which diseases are most likely to respond to a selective NMT inhibitor. We describe here the phenotype of NMT inhibition in HeLa cells and show that cells die through apoptosis following or concurrent with accumulation in the G1 phase. We used quantitative proteomics to map protein expression changes for more than 2700 proteins in response to treatment with an NMT inhibitor in HeLa cells and observed down-regulation of proteins involved in cell cycle regulation and up-regulation of proteins involved in the endoplasmic reticulum stress and unfolded protein response, with similar results in breast (MCF-7, MDA-MB-231) and colon (HCT116) cancer cell lines. This study describes the cellular response to NMT inhibition at the proteome level and provides a starting point for selective targeting of specific diseases with NMT inhibitors, potentially in combination with other targeted agents. PMID- 27267254 TI - Single-dose pharmacokinetics of ibrutinib in subjects with varying degrees of hepatic impairment. AB - This open-label, single-dose study was designed to characterize pharmacokinetics and safety profile of ibrutinib in hepatically impaired subjects. Each subject received single oral dose of ibrutinib (140 mg) following an overnight fast (hepatic impairment-mild [n = 6], moderate [n = 10], and severe [n = 8]; healthy control [n = 6]). Subjects with hepatic impairment showed significant increase in ibrutinib plasma exposures and fraction unbound ibrutinib. Compared to control group, mean exposure (AUClast; unbound) in mild, moderate, and severe cohorts was 4.1-, 9.8-, 13.4-fold higher, respectively. Terminal half-life trended slightly longer in moderately and severely impaired subjects, but risk of accumulation on repeated dosing appears negligible as half-life did not exceed 10 h. Based on observed effects on exposure, reduced doses are recommended for patients with mild and moderate liver impairment (Child-Pugh Class A and B), whereas 140 mg is considered too high for severely impaired patients (Class-C). A single dose of 140 mg was well tolerated in this study (NCT01767948). PMID- 27267255 TI - Coronary flow velocity reserve by echocardiography: feasibility, reproducibility and agreement with PET in overweight and obese patients with stable and revascularized coronary artery disease. AB - BACKGROUND: Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography of the LAD is used to assess microvascular function but validation studies in clinical settings are lacking. We aimed to assess feasibility, reproducibility and agreement with myocardial flow reserve (MFR) measured by PET in overweight and obese patients. METHODS: Participants with revascularized coronary artery disease were examined by CFVR. Subgroups were examined by repeated CFVR (reproducibility) or Rubidium-82-PET (agreement). To account for time variation, results were computed for scans performed within a week (1-week) and for all scans regardless of time gap (total) and to account for scar tissue for patients with and without previous myocardial infarction (MI). RESULTS: Eighty-six patients with median BMI 30.9 (IQR 29.4-32.9) kg * m(-2) and CFVR 2.29 (1.90-2.63) were included. CFVR was feasible in 83 (97 %) using a contrast agent in 14 %. For reproducibility overall (n = 21) limits of agreement (LOA) were (-0.75;0.71), within-subjects coefficient of variation (CV) 11 %, and reliability 0.84. For reproducibility within 1-week (n = 13) LOA were ( 0.33;0.25), within-subjects CV 5 %, and reliability 0.97. Agreement with MFR of the LAD territory (n = 35) was without significant bias and overall LOA were ( 1.40;1.46). Agreement was best for examinations performed within 1-week of participants without MI of the LAD-territory (n = 12); LOA = (-0.68;0.88). CONCLUSIONS: CFVR was highly feasible with a good reproducibility on par with other contemporary measures applied in cardiology. Agreement with MFR was acceptable, though discrepancy related to prior MI has to be considered. CFVR of LAD is a valid tool in overweight and obese patients. PMID- 27267257 TI - Automated Glycan Assembly of Complex Oligosaccharides Related to Blood Group Determinants. AB - Lactotetraosyl (Lc4) and neo-lactotetraosyl (nLc4) are backbones that are common to many glycans. Using automated glycan assembly, these common core structures were constructed and elaborated to access synthetically challenging glycans of biological relevance. The incorporation of alpha-fucoses is demonstrated for H type I and II; alpha(1,3)-galactose epitopes were prepared, and the pentasaccharide HNK-1 required incorporation of a 3-O-sulfate. In addition to preparing the target structures, essential insights were gained regarding the relationships of glycosylating agents and nucleophiles as well as the linker stability. PMID- 27267256 TI - Global research trends of Middle East respiratory syndrome coronavirus: a bibliometric analysis. AB - BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that causes severe viral pneumonia in humans, known to have a high mortality rate and a similarity in clinical symptoms with severe acute respiratory syndrome coronavirus. It was first isolated in Kingdom of Saudi Arabia (KSA) in 2012 and after that, MERS-CoV exhibited outbreaks in several regions of the world. This study aimed to assess the characteristics of publications involving MERS-CoV at global level by using a bibliometric analysis. METHODS: Scopus database was searched on March 4, 2016 for MERS-CoV publications published between 2012 and 2015. It was performed on the same day in order to avoid the possible bias came from update on the database because the metrics are changing over time. All publication types were considered; however publications as errata were excluded. Analysis parameters include year of publication, publication type, patterns of international collaboration, research institutions, journals, impact factor, h index, language, and times cited. RESULTS: A total of 883 MERS-CoV research publications were published across the world. The MERS-CoV-associated publications were originated from 92 countries/territories, indicating the international spread of MERS-CoV research. The USA was the largest contributor, with 319 articles published over 4 years, followed by KSA (113 articles). The total number of citations for these publications has already achieved 8,015, with an average of 9.01 citations per each publication. The h-index for MERS-CoV associated publications was 48. The USA also have the highest h-index (32), followed by KSA (26) and UK (22). Netherland produced the greatest proportion of publications with international research collaboration (72.7 %) followed by the UK (71 %) and Germany (69.1 %) out of the total number of publications for each country. CONCLUSIONS: There is a rapid increase in research activities related to MERS-CoV from 2012 to 2015. This study demonstrates that the MERS-CoV related literature has grown to be more extensive and global over the past 4 years. The bulk of publications in the field of MERS-CoV research are published by high income countries such as the USA. Furthermore, the USA, the UK and KSA may have higher quality of articles according to the value of h-index. PMID- 27267258 TI - Finding the experts in the crowd: Validity and reliability of crowdsourced measures of children's gradient speech contrasts. AB - Perceptual ratings aggregated across multiple nonexpert listeners can be used to measure covert contrast in child speech. Online crowdsourcing provides access to a large pool of raters, but for practical purposes, researchers may wish to use smaller samples. The ratings obtained from these smaller samples may not maintain the high levels of validity seen in larger samples. This study aims to measure the validity and reliability of crowdsourced continuous ratings of child speech, obtained through Visual Analog Scaling, and to identify ways to improve these measurements. We first assess overall validity and interrater reliability for measurements obtained from a large set of raters. Second, we investigate two rater-level measures of quality, individual validity and intrarater reliability, and examine the relationship between them. Third, we show that these estimates may be used to establish guidelines for the inclusion of raters, thus impacting the quality of results obtained when smaller samples are used. PMID- 27267259 TI - Pharmacokinetic/pharmacodynamic considerations for epilepsy - depression comorbidities. AB - INTRODUCTION: Epilepsy may be frequently associated with psychiatric disorders and its co-existence with depression usually results in the reduced quality of life of patients with epilepsy. Also, the efficacy of antiepileptic treatment in depressed patients with epilepsy may be significantly reduced. AREAS COVERED: Results of experimental studies indicate that antidepressants co-administered with antiepileptic drugs may either increase their anticonvulsant activity, remain neutral or decrease the protective action of antiepileptic drugs in models of seizures. Apart from purely pharmacodynamic interactions, pharmacokinetic mechanisms have been proven to contribute to the final outcome. We report on clinical data regarding the pharmacokinetic interactions of enzyme-inducing antiepileptic drugs with various antidepressants, whose plasma concentration may be significantly reduced. On the other hand, antidepressants (especially selective serotonin reuptake inhibitors) may influence the metabolism of antiepileptics, in many cases resulting in the elevation of plasma concentration of antiepileptic drugs. EXPERT OPINION: The preclinical data may provide valuable clues on how to combine these two groups of drugs - antidepressant drugs neutral or potentiating the anticonvulsant action of antiepileptics are recommended in this regard. Avoidance of antidepressants clearly decreasing the convulsive threshold or decreasing the anticonvulsant efficacy of antiepileptic drugs (f.e. bupropion or mianserin) in patients with epilepsy is recommended. PMID- 27267261 TI - Medical Research Volunteer Program (MRVP): innovative program promoting undergraduate research in the medical field. AB - BACKGROUND: Most educational institutions lack a structured system that provides undergraduate students with research exposure in the medical field. The objective of this paper is to describe the structure of the Medical Research Volunteer Program (MRVP) which was established at the American University of Beirut, Lebanon, as well as to assess the success of the program. METHODS: The MRVP is a program that targets undergraduate students interested in becoming involved in the medical research field early on in their academic career. It provides students with an active experience and the opportunity to learn from and support physicians, clinical researchers, basic science researchers and other health professionals. Through this program, students are assigned to researchers and become part of a research team where they observe and aid on a volunteer basis. This paper presents the MRVP's four major pillars: the students, the faculty members, the MRVP committee, and the online portal. Moreover, details of the MRVP process are provided. The success of the program was assessed by carrying out analyses using information gathered from the MRVP participants (both students and faculty). Satisfaction with the program was assessed using a set of questions rated on a Likert scale, ranging from 1 (lowest satisfaction) to 5 (highest satisfaction). RESULTS: A total of 211 students applied to the program with a total of 164 matches being completed. Since the beginning of the program, three students have each co-authored a publication in peer-reviewed journals with their respective faculty members. The majority of the students rated the program positively. Of the total number of students who completed the program period, 35.1 % rated the effectiveness of the program with a 5, 54.8 % rated 4, and 8.6 % rated 3. A small number of students gave lower ratings of 2 and 1 (1.1 % and 0.4 %, respectively). CONCLUSION: The MRVP is a program that provides undergraduate students with the opportunity to learn about research firsthand as they volunteer and aid in different research projects. This program also provides faculty members with the help to conduct their research projects and opportunity to influence future generations. It was shown that so far the MRVP has been successful in reaching its goals, for both students and faculty. PMID- 27267260 TI - Dietary conjugated linoleic acid affects blood parameters, liver morphology and expression of selected hepatic genes in laying hens. AB - The objective of this research were to investigate the effect of a conjugated linoleic acid (CLA)-enriched diet on Isa Brown laying hen health status and to provide a comprehensive analysis of changes in blood parameters, liver morphology and selected hepatic gene expression. Hens were allocated to the control and experimental group (diet enriched with 0.75% CLA) for a total period of 4 m. At the end of the experiment half of the hens from each group were slaughtered for analyses. The remaining hens were transferred to an organic farm for the next 5 m and fed on the diet without CLA supplementation. The CLA-enriched diet resulted in significant changes in blood and serum parameters; specifically, haematocrit (HCT), mean corpuscular volume (MCV) and white blood cells (WBC) count were decreased compared to the control. The total cholesterol (TC) was not significantly affected while the triacylglycerol's (TG) concentration was elevated. The activity of alanine aminotransferase (ALT) was significantly increased in the CLA-supplemented group, while aspartate aminotransferase (AST) showed an increasing tendency. Liver biopsies showed pathological changes classified as non-alcoholic fatty liver disease (NAFLD). Additionally, the expression of hepatic genes involved in fatty acids synthesis (ME1, ACLY, ACC, FASN, SCD1), oxidation (CPT1alpha, PPARA), detoxification processes (Cytochrome P450, CYP, Flavin-containing monooxygenase, FMO3), oxidative stress (NOX4, XbP1) and inflammation (IL6, TNFalpha) were elevated. Cessation of CLA supplementation for 5 m of organic farming resulted in normalisation of blood and hepatic parameters to the levels observed in control hens. The results of this study indicate that dietary CLA triggers an integrated stress response in laying hens and activates mechanisms involved in liver detoxification. PMID- 27267262 TI - A review of the new provisions for sanctioning mentally disordered offenders in China, in a broader historical context. AB - Reforms of the criminal justice system in China in recent years have included the 2012 Code of Criminal Procedure (CCP), which resulted in new disposals for mentally disordered offenders. From a Western perspective, changes in Chinese criminal law are sometimes cliched as toothless window dressing, but they may represent a genuine step forward in safeguarding human rights. Taking a historical perspective, this paper reveals that in the East, as much as in the West, there is a 'moral tradition' of not punishing mentally disordered offenders who are not considered responsible for their acts. There are clear differences in disposal for those acquitted having been found 'not guilty by reason of insanity'. Whereas Western jurisdictions have offered (criminal) courts the opportunity for commitment in (forensic) mental hospitals from the early 19th Century, in China, disposal has remained, until the recent changes, the responsibility of the administration (mainly the police) or the family of the offender. A few high profile cases brought to light the inadequacy of these arrangements and the general disregard of obvious mental health issues when sentencing offenders. There was lack of clarity regarding who would take responsibility for treatment and issues of future public protection arising from a mental disorder. The 2012 CCP introduces the power of mental health commitment by the judiciary for those found non-responsible for an offense because of a mental disorder. Similar to provisions in Western jurisdictions there remain human rights concerns regarding aspects of 2012 CCP and the role of 'preventive detention' for mentally disordered offenders on indeterminate secure mental health detention. Nevertheless, the shift to judicial decision making in such cases and the possibility of mental health commitment are welcome steps in improving the human rights of this vulnerable population. PMID- 27267263 TI - Erratum to: Unraveling the pectinolytic function of Bacteroides xylanisolvens using a RNA-seq approach and mutagenesis. PMID- 27267265 TI - Bis(dipyrrinato)zinc(II) Complexes: Emission in the Solid State. AB - This Communication reports the first observation of solid-state photoluminescence in bis(dipyrrinato)zinc(II) complexes with various substituents. The report discusses the effect of their substituents on their crystal structures and spectroscopic properties. Their meso-aryl groups are revealed to play important roles in the spectroscopic properties in the solid state. PMID- 27267264 TI - Intra-islet glucagon-like peptide 1. AB - PURPOSE: Glucagon-like peptide-1 (GLP-1) is originally identified in the gut as an incretin hormone, and it is potent in stimulating insulin secretion in the pancreas. However, increasing evidence suggests that GLP-1 is also produced locally within pancreatic islets. This review focuses on the past and current discoveries regarding intra-islet GLP-1 production and its functions. MAIN FINDINGS: There has been a long-standing debate with regard to whether GLP-1 is produced in the pancreatic alpha cells. Early controversies lead to the widely accepted conclusion that the vast majority of proglucagon is processed to form glucagon in the pancreas, whereas an insignificant amount is cleaved to produce GLP-1. With technological advancements, recent studies have shown that bioactive GLP-1 is produced locally in the pancreas, and the expression and secretion of GLP-1 within islets are regulated by various factors such as cytokines, hyperglycemia, and beta cell injury. CONCLUSIONS: GLP-1 is produced by the pancreatic alpha cells, and it is fully functional as an incretin. Therefore, intra-islet GLP-1 may exert insulinotropic and glucagonostatic effects locally via paracrine and/or autocrine actions, under both normal and diabetic conditions. PMID- 27267266 TI - Two-Dimensional Organic-Inorganic Hybrid Perovskite Photonic Films. AB - Organic-inorganic hybrid perovskites have created enormous expectations for low cost and high-performance optoelectronic devices. In prospect, future advancements may derive from reaping novel electrical and optical properties beyond pristine perovskites through microscopic structure design and engineering. Herein, we report the successful preparation of two-dimensional inverse-opal perovskite (IOP) photonic films, featuring unique nanostructures and vivid colors. Further compositional and structural managements promise optical property and energy level tunability of the IOP films. They are further functionalized in solar cells, resulting in colorful devices with respectable power conversion efficiency. Such concept has not been previously applied for perovskite-based solar cells, which could open a route for more versatile optoelectronic devices. PMID- 27267267 TI - Investor Outlook: Rising from the Ashes; GSK's European Approval of Strimvelis for ADA-SCID. AB - GlaxoSmithKline's (GSK) and partner San Raffaele Telethon Institute for Gene Therapy's recent positive European approval for Strimvelis for treatment of severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) represents the second EU-approved gene therapy and the first gamma-retrovirus and first ex vivo gene therapy. In this article we discuss the significance and implications of this historic approval for the broader gene therapy field. PMID- 27267268 TI - Efficacy of lixisenatide in patients with type 2 diabetes: A post hoc analysis of patients with diverse beta-cell function in the GetGoal-M and GetGoal-S trials. AB - AIMS: To evaluate the impact of beta-cell function on the efficacy of lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this post hoc analysis, patients from the Phase 3 GetGoal-M and GetGoal-S clinical trials randomized to lixisenatide 20MUg once daily were stratified into quartiles by baseline beta-cell function, as measured by the secretory units of islet in transplantation (SUIT) index. RESULTS: Patients (N=437) were distributed evenly among SUIT index quartiles 1 to 4 (lowest to highest beta-cell function). Clinical outcomes improved from baseline across all SUIT quartiles; mean changes at week 24 were: glycated hemoglobin (HbA1c; % [mmol/mol]), -0.99 (-10.8), -0.87 (-9.5), -0.86 (-9.4), -0.83 (-9.1); and postprandial plasma glucose (PPG; mmol/L), -7.9, -5.6, -5.5, -4.3 (overall effect P<0.0001). Furthermore, postprandial glucagon was reduced in all SUIT quartiles, while insulinogenic index improved only in patients with higher baseline SUIT (overall effect P=0.0286). No severe symptomatic hypoglycemic events were reported. CONCLUSIONS: Lixisenatide treatment resulted in reductions in HbA1c and PPG levels across all SUIT quartiles. This suggests that non-insulin-related actions of lixisenatide contribute to improved glycemic control in T2D. PMID- 27267269 TI - Expression density of receptors to IL-1beta in atopic dermatitis. AB - Interleukin 1 (IL-1 beta) and the system for regulation of its biological effects play an important role in the development and behavior of inflammatory processes in atopic dermatitis. Notably, cells that are actively involved in the pathological process have altered expression of cytokine receptors. However, standard evaluation of cells by flow cytometry measures only the percentage of cells expressing the appropriate marker, which is not enough for a full assessment of these changes. The aim of this study was to investigate changes in the expression of IL-1beta cytokine receptors in patients with atopic dermatitis by both percentage of cells with receptors in various subsets and the absolute number of membrane-bound receptors themselves. It was found that an increase or decrease in the percentage of cells expressing the receptors in subsets of immune cells in patients with atopic dermatitis was not associated with a change in the number of receptors on the cell surface. Moreover, the changes in the percentage of cells and the number of receptors may occur in different directions, as shown for IL-1R2 expression on B cells and IL-1R1 expression for monocytes. Changes in the parameters of IL-1beta receptor expressions are associated with disease severity index SCORAD in atopic dermatitis. These findings underline the importance of studying the density of cytokine receptor expression in the pathology. PMID- 27267270 TI - A novel dendritic cell-targeted lentiviral vector, encoding Ag85A-ESAT6 fusion gene of Mycobacterium tuberculosis, could elicit potent cell-mediated immune responses in mice. AB - Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), leading to high mortality worldwide. It is well-established that cellular immunity plays a critical role to control Mtb infection. Dendritic Cells (DCs) are potent antigen presenting cells, which play an important role to prime cell mediated immune responses. In vivo targeting of DCs has been shown to induce both strong cellular immunity and protection against tumor challenges. The aim of the present study was not only to assess the immunizing potential of a novel DC targeted recombinant lentivirus expressing fusion antigen Ag85A-ESAT6 of Mtb, but also to compare it with a recombinant lentivirus with broad cellular tropism expressing the same antigen in mice. The findings demonstrated that our novel recombinant DC-targeted lentivector was able to successfully transduce and express the fusion antigen Ag85A-E6 in vitro and in vivo. Moreover, a single footpad injection of targeted lentivectors could elicit strong T-helper 1 (Th1) immunity against the above mentioned antigen, as indicated by the specific high level production of IFN-gamma and IL-2 using spleen lymphocytes and lymphoproliferative responses. Despite of these promising results, more attempts are required to elucidate the protective and therapeutic efficacy of this approach in future. PMID- 27267271 TI - Esterase D enhances type I interferon signal transduction to suppress foot-and mouth disease virus replication. AB - The enzymatic activities of esterase D (ESD) are involved in many human diseases. However, no antiviral property of ESD has been described to date. Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease. In this study, we showed that FMDV infection triggered ESD expression. Overexpression of ESD significantly suppressed FMDV replication and knockdown of ESD expression enhanced virus replication, showing an essential antiviral role of ESD. Furthermore, we found that Sendai-virus-induced interferon (IFN) signaling was enhanced by upregulation of ESD, and ESD promoted activation of the IFN-beta promoter simulated by IFN regulatory factor (IRF)3 or its upstream molecules (retinoic acid-inducible gene-I, melanoma differentiation-associated protein 5, virus-induced signaling adaptor and TANK binding kinase 1). Detailed analysis revealed that ESD protein enhanced IRF3 phosphorylation during FMDV infection. Overexpression of ESD also promoted the expression of various antiviral interferon-stimulated genes (ISGs) and knockdown of ESD impaired the expression of these antiviral genes during FMDV infection. Our findings demonstrate a new mechanism evolved by ESD to enhance type I IFN signal transduction and suppress viral replication during FMDV infection. PMID- 27267272 TI - NK cells control HIV-1 infection of macrophages through soluble factors and cellular contacts in the human decidua. AB - BACKGROUND: During the first trimester of pregnancy, HIV-1 in utero transmission is rare despite the permissivity of the placenta and the decidua (the uterine mucosa during pregnancy) to infection. In the decidua from the first trimester of pregnancy, macrophages (dMs) are the HIV-1 main target cells. Decidual natural killer (dNK) cells account for 70 % of decidual leukocytes. They display distinct phenotype and functions compared to peripheral NK cells. At the periphery, NK cells are involved in the control of HIV-1 infection. In this study, we investigate whether human decidual natural killer (dNK) cells control dM HIV-1 infection. RESULTS: Autologous cocultures of infected dMs with dNK cells reveal that dNK cells strongly inhibit dM HIV-1 infection. The addition of dNK cells to dMs at different times after infection suggests that the control occurs before the complete establishment of the infection. Double chamber cocultures show that cellular contacts are necessary for an optimal control of infection. Nevertheless, soluble factors secreted by dMs and dNK cells in double chamber cocultures partially inhibit dM HIV-1 infection, indicating that soluble factors have also a role in the control of infection. IFN-gamma secretion is increased in infected and uninfected cocultures. We show that IFN-gamma is involved in the control of dM HIV-1 infection by dNK cells. CONCLUSIONS: These results demonstrate that human dNK cells inhibit efficiently HIV-1 infection in dMs in vitro, and highlight the role of innate immune determinants in the control of HIV 1 transmission. PMID- 27267273 TI - Gendered sexual uses of alcohol and associated risks: a qualitative study of Nigerian University students. AB - BACKGROUND: Alcohol misuse among young people is a global phenomenon. In many countries, young people engage in heavy drinking and this exacerbates risky sexual behaviour. In Nigeria, alcohol held multiple roles in the traditional era but was mainly consumed by adult males for pleasure. Adult females and young people were culturally constrained from drinking in most communities. In contemporary Nigeria, young people's drinking is increasing, and many engage in sexual intercourse under the influence of alcohol. METHODS: This study draws on the traditional gender and social sexual scripts to explore the factors that motivate young people to use alcohol for sexual purposes. In-depth interviews were conducted with 19 to 23-year old male and female undergraduate students from a Nigerian university. Thematic analysis was conducted with the aid of NVivo 10 software. RESULTS: Men drink to become confident to initiate sexual relationships, stimulate sexual urges, prolong erection, increase sexual satisfaction and become more aggressive during sexual intercourse. Women also drink to be bold in initiating sexual relationships, for sexual arousal and to increase satisfaction. Relatedly, not every brand of alcohol is used for sexual purposes. For example, while men use 'herbal' alcoholic beverages and a mixture of locally-produced gin and marijuana, women use champagne and other flavoured alcoholic beverages. The results also revealed that young people use alcohol or salt in a bid to prevent conception after sexual intercourse. CONCLUSIONS: Adherence to the traditional gender (masculinity) and social sexual scripts amongst men and the enactment of what appears to be a new form of femininity script amongst women contribute to a culturally specific understanding of the motivations to use alcohol for sexual purposes. Evidence-based strategies should be employed to distribute information about the consequences of sexual intercourse under the influence of alcohol. PMID- 27267276 TI - Resisting the onset of herbivore attack: plants perceive and respond to insect eggs. AB - Plants can respond to attack by herbivorous insects very soon after herbivores start producing a new generation by depositing eggs onto their leaves. Egg induced plant responses may result in killing the attacker in its egg stage. However, if the eggs do survive, they can also prime feeding-induced plant defenses against the larvae hatching from eggs. In this paper we focus first on egg-induced plant responses that resemble hypersensitive responses (HR) to phytopathogens and lead to egg desiccation or detachment from plants. We then summarize the current knowledge about egg-mediated effects on feeding-induced plant defenses against larvae. Finally, we discuss the insect species specificity of plant responses to eggs and the variability of insect susceptibility to these responses. PMID- 27267274 TI - An Unrecognized Function of Cholesterol: Regulating the Mechanism Controlling Membrane Phospholipid Asymmetry. AB - An asymmetric distribution of phospholipids in the membrane bilayer is inseparable from physiological functions, including shape preservation and survival of erythrocytes, and by implication other cells. Aminophospholipids, notably phosphatidylserine (PS), are confined to the inner leaflet of the erythrocyte membrane lipid bilayer by the ATP-dependent flippase enzyme, ATP11C, counteracting the activity of an ATP-independent scramblase. Phospholipid scramblase 1 (PLSCR1), a single-transmembrane protein, was previously reported to possess scrambling activity in erythrocytes. However, its function was cast in doubt by the retention of scramblase activity in erythrocytes of knockout mice lacking this protein. We show that in the human erythrocyte PLSCR1 is the predominant scramblase and by reconstitution into liposomes that its activity resides in the transmembrane domain. At or below physiological intracellular calcium concentrations, total suppression of flippase activity nevertheless leaves the membrane asymmetry undisturbed. When liposomes or erythrocytes are depleted of cholesterol (a reversible process in the case of erythrocytes), PS quickly appears at the outer surface, implying that cholesterol acts in the cell as a powerful scramblase inhibitor. Thus, our results bring to light a previously unsuspected function of cholesterol in regulating phospholipid scrambling. PMID- 27267277 TI - Plant phenotypic plasticity in the phytobiome: a volatile issue. AB - Plants live in a diverse and dynamic phytobiome, consisting of a microbiome as well as a macrobiome. They respond to arthropod herbivory with the emission of herbivore-induced plant volatiles (HIPV) that are public information and can be used by any member of the phytobiome. Other members of the phytobiome, which do not directly participate in the interaction, may both modulate the induction of HIPV in the plant, as well as respond to the volatiles. The use of HIPV by individual phytobiome members may have beneficial as well as detrimental consequences for the plant. The collective result of phytobiome-modulated HIPV emission on the responses of phytobiome members and the resulting phytobiome dynamics will determine whether and under which circumstances HIPV emission has a net benefit to the plant or not. Only when we understand HIPV emission in the total phytobiome context can we understand the evolutionary consequences of HIPV emission by plants. PMID- 27267278 TI - Photo-induced interaction of thioglycolic acid (TGA)-capped CdTe quantum dots with cyanine dyes. AB - The photo-induced interaction of three different sizes of thioglycolic acid (TGA) capped CdTe quantum dots (CdTe QDs) with two monomethine cyanine dyes belonging to the thiazole orange (TO) family has been studied. Positively charged cyanines interact with QDs surface which is negatively charged due to capping agent carboxylate ions. The energy transfer parameters including Stern-Volmer constant, Ksv, number of binding sites, n, quenching sphere radius, r, the critical energy transfer distance, R0, and energy transfer efficiencies, E have been calculated. The effect of structure and the number of aggregating molecules have been studied as a function of CdTe QDs particle size. Combining organic and inorganic semiconductors leads to increase of the effective absorption cross section of the QDs which can be utilized in novel nanoscale designs for light-emitting, photovoltaic and sensor applications. A synthesized triplet emission of the studied dyes was observed using CdTe QDs as donors and this is expected to play a potential role in molecular oxygen sensitization and in photodynamic therapy (PDT) applications. PMID- 27267279 TI - Analysis of binding ability of two tetramethylpyridylporphyrins to albumin and its complex with bilirubin. AB - An interaction between 5,10,15,20-tetrakis-(N-methyl-x-pyridyl)porphyrins, x=2; 4 (TMPyPs) with bovine serum albumin (BSA) and its bilirubin (BR) complex was investigated by UV-Viz and fluorescence spectroscopy under imitated physiological conditions involving molecular docking studies. The parameters of forming intermolecular complexes (binding constants, quenching rate constants, quenching sphere radius etc.) were determined. It was showed that the interaction between proteins and TMPyPs occurs via static quenching of protein fluorescence and has predominantly hydrophobic and electrostatic character. It was revealed that obtained complexes are relatively stable, but in the case of TMPyP4 binding with proteins occurs better than TMPyP2. Nevertheless, both TMPyPs have better binding ability with free protein compared to BRBSA at the same time. The influence of TMPyPs on the conformational changes in protein molecules was studied using synchronous fluorescence spectroscopy. It was found that there is no competition of BR with TMPyPs for binging sites on protein molecule and BR displacement does not occur. Molecular docking calculations have showed that TMPyPs can bind with albumin via tryptophan residue in the hydrophilic binding site of protein molecule but it is not one possible interaction way. PMID- 27267280 TI - Off-On-Off fluorescence behavior of an intramolecular charge transfer probe toward anions and CO2. AB - The photophysical behavior of a newly developed fluorescent probe, tricyanoethylphenyl phenanthroimidazole (TCPPI) has been studied. Upon interaction of different class of anions TCPPI displayed naked-eye sensitive fluorescence "turn-on" response to detect selectively F(-) (0.98MUM, 18.62ppb) and CN(-) (1.12MUM, 29.12ppb) anions in acetonitrile (MeCN). Job's plot analysis revealed a 1:1 binding stoichiometry between probe and anions. The spectral data analysis and 1H NMR titration studies suggested about the affinity of F(-) and CN(-) anions with moderately acidic -NH fragment of imidazolyl unit of probe through deprotonation and H-bonding interaction. Moreover, the anion activated probe upon interaction with CO2 revived photophysical properties of probe, "On Off-On" type fluorescence and enabled anion-induced CO2 sensing in the medium. PMID- 27267281 TI - Using FTIR-photoacoustic spectroscopy for phosphorus speciation analysis of biochars. AB - In the last decade, numerous studies have evaluated the benefits of biochar for improving soil quality. The purposes of the current study were to use Fourier transform infrared-photoacoustic spectroscopy (FTIR-PAS) to analyse P species in biochar and to determine the effect of pyrolysis temperature on P speciation. The photoacoustic detector has a range of advantages for the very dark biochar samples in comparison to more traditional reflectance or transmission FTIR detectors. The spectra turned out to be more informative in the regions with P vibrations for biochar produced at temperatures above 400 degrees C, where most of the remaining organic compounds were aromatic and therefore not overlapping with the P vibrations. For biochars produced from the solid fraction of digestate from biogas production, an increase in the pyrolysis temperature led to the formation of a large variety of P species. Hydroxylapatite and tricalcium phosphate were the most dominant P species in the mid to high temperature range (600-900 degrees C), while at 1050 degrees C apatite, iron phosphates, variscite and calcium phosphates were identified. However, the changes in P speciation in biochars produced from bone meal at different temperatures were smaller than in the biochars from digestate. Hydroxylapatite and calcium phosphates were identified in biochar produced at all temperatures, while there was some indication of struvite formation. PMID- 27267282 TI - A novel colorimetric and turn-on fluorescent chemosensor for iron(III) ion detection and its application to cellular imaging. AB - A novel rhodamine-based dual probe Rh-2 for trivalent ferric ions (Fe(3+)) was successfully designed and synthesized, which exhibited a highly sensitive and selective recognition towards Fe(3+) with an enhanced fluorescence emission in methanol-water media (v/v=7/3, pH=7.2). The probe Rh-2 could be applied to the determination of Fe(3+) with a linear range covering from 3.0*10(-7) to 1.4*10( 5)M and a detection limit of 1.24*10(-8)M. Meanwhile, the binding ratio of Rh-2 and Fe(3+) was found to be 1:1. Most importantly, the fluorescence and color signal changes of the Rh-2 solution were specific to Fe(3+) over other commonly coexistent metal ions. Moreover, the probe Rh-2 has been used to image Fe(3+) in living cells with satisfying results. PMID- 27267283 TI - Theoretical and experimental studies of the stability of drug-drug interact. AB - Several factors can intervene in the molecular properties and consequently in the stability of drugs. The molecular complexes formation often occur due to favor the formation of hydrogen bonds, leading the system to configuration more energy stable. This work we aim to investigate through theoretical and experimental methods the relation between stability and properties of molecular complexes the molecular complex formed between the drugs, efavirenz (EFV), lamivudine (3TC) and zidovudine (AZT). With this study was possible determining the most stable complex formed between the compounds evaluated. In addition the energy and structural properties of the complex formed in relation to its individual components allowed us to evaluate the stability of the same. PMID- 27267284 TI - Discovering "The Italian Flag" by Fernando Melani (1907-1985). AB - In the occasion of the celebrations for the 150th anniversary of the founding of Italy (1861-2011), it was decided to analyse the artwork "The Italian Flag" (La Bandiera Italiana) created by the artist Fernando Melani (Pistoia, 1907-1985), one of the precursors of the Poor Art artistic movement in Italy. This project is a follow-up to a previous study which was mainly focused on the pigments and dyes found in his home-studio. The main goal of this paper is to identify a correct diagnostic plan, based on the use of a combination of non-invasive and micro invasive methodologies, in order to determine the state of preservation and define the best conservation procedures for a contemporary artwork. Visible, infrared and infrared false colour images as well as the Fibre Optic Reflectance Spectroscopy (FORS) technique were applied in situ to analyse The Italian Flag. Laser Induced Breakdown Spectroscopy (LIBS), Fourier Transform Infrared (FT-IR) and micro-Raman spectroscopies, Pyrolysis-Gas Chromatography/Mass Spectroscopy (Py-GC/MS), High Performance Liquid Chromatography with Diode Arrays Detection (HPLC-DAD) and Mass Spectrometric Detection (HPLC-ESI-Q-ToF) were all applied to three small samples detached from the three painted (green-blue, white and red yellow, respectively) areas of the flag. The combination of the data obtained with all these techniques made possible a comprehensive understanding of both the chemical composition and physical behaviour of the materials used by the artist and supported curators in defining the preventive conservation of this artwork. PMID- 27267285 TI - Fungal Endocarditis: Update on Diagnosis and Management. AB - Fungal endocarditis is an extremely debilitating disease associated with high morbidity and mortality. Candida spp. are the most common isolated organisms in fungal endocarditis. It is most prevalent in patients who are immunosuppressed and intravenous drug users. Most patients present with constitutional symptoms, which are indistinguishable from bacterial endocarditis, hence a high index of suspicion is required for pursuing diagnosis. Diagnosis of fungal endocarditis can be very challenging: most of the time, blood cultures are negative or take a long time to yield growth. Fungal endocarditis mandates an aggressive treatment strategy. A medical and surgical combined approach is the cornerstone of therapy. PMID- 27267286 TI - Prevention of Medical Events During Air Travel: A Narrative Review. AB - Prior to traveling, and when seeking medical pretravel advice, patients consult their personal physicians. Inflight medical issues are estimated to occur up to 350 times per day worldwide (1/14,000-40,000 passengers). Specific characteristics of the air cabin environment are associated with hypoxia and the expansion of trapped gases into body cavities, which can lead to harm. The most frequent medical events during air travel include abdominal pain; ear, nose, and throat pathologies; psychiatric disorders; and life-threatening events such as acute respiratory failure or cardiac arrest. Physicians need to be aware of the management of these conditions in this unusual setting. Chronic respiratory and cardiovascular diseases are common and are at increased risk of acute exacerbation. Physicians must be trained in these conditions and inform their patients about their prevention. PMID- 27267287 TI - An Uncharted Constellation: TAFRO Syndrome. PMID- 27267288 TI - Grim Messenger: Virchow's Node Presenting with Virchow's Triad. PMID- 27267289 TI - Prediction of Renal Allograft Acute Rejection Using a Novel Non-Invasive Model Based on Acoustic Radiation Force Impulse. AB - Point shear wave elastography based on acoustic radiation force impulse is a novel technology used to quantify tissue stiffness by measuring shear wave speed. A total of 115 kidney transplantation recipients were consecutively enrolled in this prospective study. The patients were subdivided into two groups using 1 mo post-transplantation as the cutoff time for determining the development of acute rejection (AR). Shear wave speed was significantly higher in the AR group than in the non-AR group. We created a model called SEV, comprising shear wave speed, estimated glomerular filtration rate and kidney volume change, that could successfully discriminate patients with or without AR. The area under the receiver operating characteristic curve of SEV was 0.89, which was higher than values for other variables; it was even better in patients within 1 mo post transplantation (0.954), but was lower than the estimated glomerular filtration rate in patients after 1 mo post-transplantation. Therefore, the SEV model may predict AR after renal transplantation with a high degree of accuracy, and it may be more useful in the early post-operative stage after renal transplantation. PMID- 27267291 TI - Impact of disease-causing mutations on inter-domain interactions in cMyBP-C: a steered molecular dynamics study. AB - The molecular interactions of the sarcomeric proteins are essential in the regulation of various cardiac functions. Mutations in the gene MYBPC3 coding for cardiac myosin-binding protein-C (cMyBP-C), a multi-domain protein, are the most common cause of hypertrophic cardiomyopathy (HCM). The N-terminal complex, C1 motif-C2 is a central region in cMyBP-C for the regulation of cardiac muscle contraction. However, the mechanism of binding/unbinding of this complex during health and disease is unknown. Here, we study possible mechanisms of unbinding using steered molecular dynamics simulations for the complex in the wild type, in single mutations (E258K in C1, E441K in C2), as well as in a double mutation (E258K in C1 + E441K in C2), which are associated with severe HCM. The observed molecular events and the calculation of force utilized for the unbinding suggest the following: (i) double mutation can encourage the formation of rigid complex that required large amount of force and long-time to unbind, (ii) C1 appears to start to unbind ahead of C2 regardless of the mutation, and (iii) unbinding of C2 requires larger amount of force than C1. This molecular insight suggests that key HCM-causing mutations might significantly modify the native affinity required for the assembly of the domains in cMyBP-C, which is essential for normal cardiac function. PMID- 27267292 TI - Overweight during childhood and internalizing symptoms in early adolescence: The mediating role of peer victimization and the desire to be thinner. AB - BACKGROUND: Overweight is associated with depression and anxiety among adults. It is unclear whether this association begins in childhood. Overweight among children is associated with a higher risk of peer victimization, and may mediate an association between overweight and internalizing symptoms. No study has tested this hypothesis in a longitudinal population-based sample using developmental trajectories of overweight in middle childhood. METHODS: Data was drawn from the population-based Quebec Longitudinal Study of Child Development. A three-group trajectory model of overweight development (6-12 years) was previously identified using a semi-parametric group-based approach (n=1678): "early-onset" (11.0%), "late-onset" (16.6%) and "never overweight" (72.5%). Mediation models tested the link between overweight status and child-reported depression and anxiety at 13 years via peer victimization and body dissatisfaction. RESULTS: Children on an early-onset overweight trajectory were at increased risk for both depression (B=.318, 95% CI=.141;.496) and anxiety (B=.262, 95% CI=.09;.44) at 13 years. These direct associations were mediated by peer victimization and subsequent desire to be thinner. Children on a late-onset childhood overweight trajectory were at increased risk for both depression (B=.332, 95% CI=.187;.477) and anxiety (B=.215; 95% CI=.072;.358) at 13 years, mediated by the desire to be thinner. LIMITATIONS: We were unable to control for previous levels of body dissatisfaction. Our measure of peer victimization was not specific to weight based teasing. CONCLUSIONS: Overweight during middle childhood increases risk of early adolescence internalizing symptoms. Peer victimization and body dissatisfaction are partly responsible for this link. PMID- 27267293 TI - Comorbidity between bipolar disorder and borderline personality disorder: Prevalence, explanatory theories, and clinical impact. AB - BACKGROUND: The relationship between bipolar disorder (BD) and borderline personality disorder (BPD) has been controversial and widely debated. Specifically, the comorbidity between both disorders has yielded a plethora of research, but there are no comprehensive reviews on this issue. OBJECTIVE: To determine the empirical evidence regarding the comorbidity between BD and BPD based on prevalence data, explanatory theories for their co-occurrence, and clinical impact of one disorder in the other. METHOD: A comprehensive search of databases (PubMed and PsycINFO) was performed. Published manuscripts between January 1985 and August 2015 were identified. Overall, 70 studies fulfilled inclusion criteria. RESULTS: Over a fifth of subjects showed comorbidity between BPD and BD. Empirical evidence from common underlying factors was inconclusive, but BPD appears to be a risk factor for BD. Data also indicated that the negative impact of BPD in BD (e.g., suicidality, worse mood course) was greater than vice verse. CONCLUSIONS: Given the high prevalence of comorbidity between BD and BPD and the negative effects of BPD in subjects with BD, further studies are needed to clarify the factor associated with the comorbidity between these two disorders. This information is important to develop appropriate treatments for subjects with both disorders, improve their clinical course, and prevent the increased risk of suicidality commonly found in these subjects. PMID- 27267294 TI - Depression with melancholic features is associated with higher long-term risk for dementia. AB - BACKGROUND: Depression has been reported to increase the risk of subsequently developing dementia, but the nature of this relation remains to be elucidated. Depression can be a prodrome/manifestation of dementia or an early risk factor, and the effect may differ according to depression subtypes. Our aim was to study the association between early-onset depression and different depression subtypes, and the later occurrence of dementia. METHODS: We conducted a cohort study including 322 subjects with depression, recruited between 1977 and 1984. A comparison cohort (non-exposed) was recruited retrospectively, to include 322 subjects admitted at the same hospital for routine surgery (appendicectomy or cholecystectomy), at the same period as the depressed cohort. Subjects were contacted again between 2009 and 2014, to assess their dementia status. We computed the risk for dementia in subjects with early onset depression and quantified the association between different depression subtypes (namely melancholic, anxious, and psychotic) and dementia. RESULTS: The odds of dementia were increased by 2.90 times (95% C.I. 1.61-5.21; p<0.0001) for the depressed cohort when compared to the surgical cohort. When the analysis was restricted to patients younger than 45 years old at baseline, the odds for dementia in the depressed cohort were also significantly higher when compared to the surgical cohort (8.53; 95% C.I. 2.40-30.16). In the multivariate Cox analysis, subjects having depression with melancholic features had an increased risk for developing dementia compared to those without melancholic features (HR=3.64; 95% C.I. 1.78 11.26; p=0.025). LIMITATIONS: About 59% of the participants with depression and 53% of those non-exposed were lost during follow up. The inclusion of biological biomarkers would strengthen the results. The sample included a low number of bipolar patients. CONCLUSIONS: These results support depression as an early risk factor for dementia. Depression with melancholic features was found as an important risk factor for dementia, playing a main role in the relation between these disorders. PMID- 27267295 TI - Long-term relationships between perceived social support and posttraumatic stress after the 2011 Oslo bombing: A three-year longitudinal study. AB - BACKGROUND: After traumatic events, social support and posttraumatic stress are interrelated, but little is known about the underlying dynamics behind this association. Levels of social support and posttraumatic stress may change and affect each other over time, but there are also stable time-invariant individual differences in both constructs. The present study aimed to determine the amount of variance explained by stable individual differences in levels of social support and posttraumatic stress across three years, and to determine whether and to what extent social support and posttraumatic stress may affect one another when these stable individual differences are controlled for. METHODS: We used data from ministerial employees present in the Governmental district during the 2011 Oslo bombing attack (N=255). Data was collected ten months, two years, and three years after the terror attack. Using a random intercept cross lagged panel model (RI-CLPM), we tested the possible directional effects between social support and posttraumatic stress within persons when variance between persons was taken into account. RESULTS: The intraclass correlations of the three measures of posttraumatic stress and social support were.83 and.74, respectively. The remaining variation within persons could not be explained by change in either of these constructs. LIMITATION: We have no information on the processes that might have occurred before 10 months after the incident. CONCLUSIONS: Our findings indicate that the long-term longitudinal linkage between social support and posttraumatic stress may be best explained by stable individual differences rather than causal processes operating within persons. PMID- 27267296 TI - General AMBER Force Field Parameters for Diphenyl Diselenides and Diphenyl Ditellurides. AB - The General AMBER Force Field (GAFF) has been extended to describe a series of selenium and tellurium diphenyl dichalcogenides. These compounds, besides being eco-friendly catalysts for numerous oxidations in organic chemistry, display peroxidase activity, i.e., can reduce hydrogen peroxide and harmful organic hydroperoxides to water/alcohols and as such are very promising antioxidant drugs. The novel GAFF parameters are tested in MD simulations in different solvents and the (77)Se NMR chemical shift of diphenyl diselenide is computed using structures extracted from MD snapshots and found in nice agreement with the measured value in CDCl3. The whole computational protocol is described in detail and integrated with in-house code to allow easy derivation of the force field parameters for analogous compounds as well as for Se/Te organocompounds in general. PMID- 27267298 TI - Inhalation devices: from basic science to practical use, innovative vs generic products. AB - INTRODUCTION: Inhalation therapy is a convenient method of treating respiratory diseases. The key factors required for inhalation are the preparation of drug carriers (aerosol particles) allowing reproducible dosing during administration. These technical challenges are accomplished with a variety of inhalation devices (inhalers) and medicinal formulations, which are optimized to be easily converted into inhalable aerosols. Areas covered: This review is focused on the most important, but often overlooked, effects, which are required for the reliable and reproducible inhalable drug administration. The effects of patient-related issues that influence inhalation therapy, such as proper selection of inhalers for specific cases is discussed. We also discuss factors that are the most essential if generic inhalation product should be considered equivalent to the drugs with the clinically confirmed efficacy. Expert opinion: Proper device selection is crucial in clinical results of inhalation therapy. The patients' ability to coordinate inhalation with actuation, generation of optimal flow through the device, use of optimal inspiratory volume, all produces crucial effects on disease control. Also the severity of the disease process effects proper use of inhalers. Interchanging of inhalers can produce potentially conflicting problem regarding efficacy and safety of inhalation therapy. PMID- 27267299 TI - Multiscale modelling approaches for assessing cosmetic ingredients safety. AB - The European Union's ban on animal testing for cosmetic ingredients and products has generated a strong momentum for the development of in silico and in vitro alternative methods. One of the focus of the COSMOS project was ab initio prediction of kinetics and toxic effects through multiscale pharmacokinetic modeling and in vitro data integration. In our experience, mathematical or computer modeling and in vitro experiments are complementary. We present here a summary of the main models and results obtained within the framework of the project on these topics. A first section presents our work at the organelle and cellular level. We then go toward modeling cell levels effects (monitored continuously), multiscale physiologically based pharmacokinetic and effect models, and route to route extrapolation. We follow with a short presentation of the automated KNIME workflows developed for dissemination and easy use of the models. We end with a discussion of two challenges to the field: our limited ability to deal with massive data and complex computations. PMID- 27267300 TI - Unexpected link between MAX and meiotic onset. PMID- 27267297 TI - Hepatitis C virus vaccine candidates inducing protective neutralizing antibodies. AB - INTRODUCTION: With more than 150 million chronically infected people, hepatitis C virus (HCV) remains a substantial global health burden. Direct-acting antivirals have dramatically improved viral cure. However, limited access to therapy, late stage detection of infection and re-infection following cure illustrate the need for a vaccine for global control of infection. Vaccines with induction of neutralizing antibodies (nAbs) have been shown to protect successfully against infections by multiple viruses and are currently developed for HCV. Areas covered: Here we review the progress towards the development of vaccines aiming to confer protection against chronic HCV infection by inducing broadly nAbs. The understanding or viral immune evasion in infected patients, the development of novel model systems and the recent structural characterization of viral envelope glycoprotein E2 has markedly advanced our understanding of the molecular mechanisms of virus neutralization with the concomitant development of several vaccine candidates. Expert commentary: While HCV vaccine development remains challenged by the high viral diversity and immune evasion, marked progress in HCV research has advanced vaccine design. Several vaccine candidates have shown robust induction of nAbs in animal models and humans. Randomized clinical trials are the next step to assess their clinical efficacy for protection against chronic infection. PMID- 27267302 TI - How reliable are randomised controlled trials for studying the relationship between diet and disease? A narrative review. AB - Large numbers of randomised controlled trials (RCT) have been carried out in order to investigate diet-disease relationships. This article examines eight sets of studies and compares the findings with those from epidemiological studies (cohort studies in seven of the cases). The studies cover the role of dietary factors in blood pressure, body weight, cancer and heart disease. In some cases, the findings from the two types of study are consistent, whereas in other cases the findings appear to be in conflict. A critical evaluation of this evidence suggests factors that may account for conflicting findings. Very often RCT recruit subjects with a history of the disease under study (or at high risk of it) and have a follow-up of only a few weeks or months. Cohort studies, in contrast, typically recruit healthy subjects and have a follow-up of 5-15 years. Owing to these differences, findings from RCT are not necessarily more reliable than those from well-designed prospective cohort studies. We cannot assume that the results of RCT can be freely applied beyond the specific features of the studies. PMID- 27267301 TI - A rating of perceived exertion scale using facial expressions for conveying exercise intensity for children and young adults. AB - OBJECTIVES: To design a rating of perceived exertion (RPE) scale using facial expressions and assessed the validity of the scale for both children and young adults. DESIGN: Pearson moment-product correlation analysis was used to assess the correlation among heart rate (HR), RPE and pedaling workload. METHODS: Fifteen children and 15 young adults participated in the study. Each participant randomly performed 5 pedaling tests with one repetition based on their submaximal acceptable workloads. Under each load condition, participants pedaled on a cycle ergometer for 10min; subsequently, participants completed Borg category ratio (CR10) or facial RPE (FRPE) scale assessments. Participants' heart rates (HR) were used to compare their scores on the Borg CR10 and Facial RPE scales. RESULTS: The results show that both Borg CR10 and FRPE scales reflected different pedaling workload levels. For young adults, HR positively correlated with both RPE scores under the various workload levels (r=0.989 and 0.977, all p<0.005); for children, only FRPE scores were positively correlated with HR (r=0.908, p<0.05). In other words, FRPE scores effectively reflected the HR of children, whereas Borg CR10 scores did not. CONCLUSIONS: The children may not understand words as effectively as young adults did, however, they understand facial expressions. The FRPE scale proposed in this study may be available in some special cases because it can assess those who cannot comprehend the written words used for the scale. PMID- 27267303 TI - Metabolomics Insights into the Modulatory Effects of Long-Term Low Calorie Intake in Mice. AB - There is increasing evidence that calorie restriction without malnutrition can extend longevity and delay the onset of age-associated disorders. Identifying the biochemical perturbations associated with different dietary habits would provide valuable insights into associations between metabolism and longevity. To reveal the effects of long-term dietary interventions on metabolic perturbations, we investigated serum and urinary metabolic changes induced by interactive high/low fat diet in combination with/without reduced caloric intake over a life span in mice using NMR-based metabonomics. We found that the high calorie dietary regime disturbed lipid metabolism, suppressed glycolysis and TCA cycles, stimulated oxidative stress, promoted nucleotide metabolism and gluconeogenesis, and perturbed gut microbiota-host interactions. Such changes could be modified by long-term low calorie intake. Most importantly, we found that the calorie intake index exerts a dominant effect on metabolic perturbations irrespective of dietary regime. Our investigation provides a holistic view of the metabolic impact of long-term dietary interventions, which are important for detecting physiological changes and dietary effects on mammalian metabolism. PMID- 27267304 TI - Characterization and identification of differentially expressed microRNAs during the process of the peribiliary fibrosis induced by Clonorchis sinensis. AB - Clonorchis sinensis (C. sinensis) infection can lead to biliary fibrosis. MicroRNAs (miRNAs) play important roles in regulation of genes expression in the liver diseases. However, the differential expression of miRNAs that probably regulates the portal fibrogenesis caused by C. sinensis has not yet been investigated. Hepatic miRNAs expression profiles from C. sinensis-infected mice at different time-points were analyzed by miRNA microarray and validated by quantitative real-time PCR (qRT-PCR). 349 miRNAs were differentially expressed in the liver of the C. sinensis-infected mice at 2, 8 or 16weeks post infection (p.i.), compared with those at 0week p.i., and there were 143 down-regulated and 206 up-regulated miRNAs among them. These all dysregulated miRNAs were potentially involved in the pathological processes of clonorchiasis by regulation of cancer-related signaling pathway, TGF-beta signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway, PI3K /AKT signaling pathway, etc. 169 of these dysregulated miRNAs were predicted to be involved in the TGF/Smads signaling pathway which plays an important role in the biliary fibrosis caused by C. sinensis. Additionally, miRNA-32, miRNA-34a, miRNA-125b and miRNA-497 were negatively correlated with Smad7 expression, indicating these miRNAs may specifically down-regulate Smad7 expression and participate in regulation of biliary fibrosis caused by C. sinensis. The results of the present study for the first time demonstrated that miRNAs were differentially expressed in the liver of mice infected by C. sinensis, and these miRNAs may play important roles in regulation of peribiliary fibrosis caused by C. sinensis, which may provide possible therapeutic targets for clonorchiasis. PMID- 27267305 TI - High prevalence of HBV/A1 subgenotype in native south Americans may be explained by recent economic developments in the Amazon. AB - Native American populations present the highest prevalence of Hepatitis B Virus (HBV) infection in the Americas, which may be associated to severe disease outcomes. Ten HBV genotypes (A-J) have been described, displaying a remarkable geographic structure, which most likely reflects historic patterns of human migrations. In this study, we characterize the HBV strains circulating in a historical sample of Native South Americans to characterize the historical viral dynamics in this population. The sample consisted of 1070 individuals belonging to 38 populations collected between 1965 and 1997. Presence of HBV DNA was checked by quantitative real-time PCR, and determination of HBV genotypes and subgenotypes was performed through sequencing and phylogenetic analysis of a fragment including part of HBsAg and Pol coding regions (S/Pol). A Bayesian Skyline Plot analysis was performed to compare the viral population dynamics of HBV/A1 strains found in Native Americans and in the general Brazilian population. A total of 109 individuals were positive for HBV DNA (~ 10%), and 70 samples were successfully sequenced and genotyped. Subgenotype A1 (HBV/A1), related to African populations and the African slave trade, was the most prevalent (66-94%). The Skyline Plot analysis showed a marked population expansion of HBV/A1 in Native Americans occurring more recently (1945-1965) than in the general Brazilian population. Our results suggest that historic processes that contributed to formation of HBV/A1 circulating in Native American are related with more recent migratory waves towards the Amazon basin, which generated a different viral dynamics in this region. PMID- 27267306 TI - Generation of Hydrogen and Methane during Experimental Low-Temperature Reaction of Ultramafic Rocks with Water. AB - Serpentinization of ultramafic rocks is widely recognized as a source of molecular hydrogen (H2) and methane (CH4) to support microbial activity, but the extent and rates of formation of these compounds in low-temperature, near-surface environments are poorly understood. Laboratory experiments were conducted to examine the production of H2 and CH4 during low-temperature reaction of water with ultramafic rocks and minerals. Experiments were performed by heating olivine or harzburgite with aqueous solutions at 90 degrees C for up to 213 days in glass bottles sealed with butyl rubber stoppers. Although H2 and CH4 increased steadily throughout the experiments, the levels were very similar to those found in mineral-free controls, indicating that the rubber stoppers were the predominant source of these compounds. Levels of H2 above background were observed only during the first few days of reaction of harzburgite when CO2 was added to the headspace, with no detectable production of H2 or CH4 above background during further heating of the harzburgite or in experiments with other mineral reactants. Consequently, our results indicate that production of H2 and CH4 during low-temperature alteration of ultramafic rocks may be much more limited than some recent experimental studies have suggested. We also found no evidence to support a recent report suggesting that spinels in ultramafic rocks may stimulate H2 production. While secondary silicates were observed to precipitate during the experiments, formation of these deposits was dominated by Si released by dissolution of the glass bottles, and reaction of the primary silicate minerals appeared to be very limited. While use of glass bottles and rubber stoppers has become commonplace in experiments intended to study processes that occur during serpentinization of ultramafic rocks at low temperatures, the high levels of H2, CH4, and SiO2 released during heating indicate that these reactor materials are unsuitable for this purpose. KEY WORDS: Serpentinization-Hydrogen generation-Abiotic methane synthesis. Astrobiology 16, 389-406. PMID- 27267308 TI - American Indian/Alaska Native Elders: A Growing Demographic that Is Changing How We View Aging. AB - Today, AIAN Elders are more actively engaged in their families and communities, encouraging the development of intergenerational programs, language and cultural revitalization, being stewards in research conducted in their communities, as well passing on their knowledge and experiences on how to live as healthy Native people. Elders have traditionally been quiet and observant of their environment, but the current and future cohorts of Elders are advocates, leaders, and culture bearers for their families and communities and they are now in positions of leadership. Western society acknowledges the value of traditional knowledge and AIAN Elders are viewed as exemplars of healthy aging and their lessons and experiences can be attributed to our own lives. This commentary highlights the paradigm shift in how society views older adults, specifically AIAN Elders and their role in health and wellbeing. PMID- 27267307 TI - Influence of DNA-Microbubble Coupling on Contrast Ultrasound-Mediated Gene Transfection in Muscle and Liver. AB - BACKGROUND: Contrast ultrasound-mediated gene delivery (CUMGD) is a promising approach for enhancing gene therapy that relies on microbubble (MB) cavitation to augment complementary deoxyribonucleic acid (cDNA) transfection. The aims of this study were to determine optimal conditions for charge-coupling cDNA to MBs and to evaluate the advantages of surface loading for gene transfection in muscle and liver. METHODS: Charge coupling of fluorescently labeled cDNA to either neutral MBs (MBN) or cationic MBs (MB+) in low- to high-ionic conditions (0.3%-1.8% NaCl) was assessed by flow cytometry. MB aggregation from cDNA coupling was determined by electrozone sensing. Tissue transfection of luciferase in murine hindlimb skeletal muscle and liver was made by CUMGD with MBN or MB+ combined with subsaturated, saturated, or supersaturated cDNA concentrations (2.5, 50, and 200 MUg/10(8) MBs). RESULTS: Charge-coupling of cDNA was detected for MB+ but not MBN. Coupling occurred over almost the entire range of ionic conditions, with a peak at 1.2% NaCl, although electrostatic interference occurred at >1.5% NaCl. DNA-mediated aggregation of MB+ was observed at <=0.6% NaCl but did not reduce the ability to produce inertial cavitation. Transfection with CUMGD in muscle and liver was low for both MBs at subsaturation concentrations. In muscle, higher cDNA concentrations produced a 10-fold higher degree of transfection with MB+, which was approximately fivefold higher (P < .05) than that for MBN. There was no effect of DNA supersaturation. The same pattern was seen for liver except that supersaturation further increased transfection with MBN equal to that of MB+. CONCLUSIONS: Efficient charge-coupling of cDNA to MB+ but not MBN occurs over a relatively wide range of ionic conditions without aggregation. Transfection with CUMGD is much more efficient with charge-coupling of cDNA to MBs and is not affected by supersaturation except in the liver, which is specialized for macromolecular and cDNA uptake. PMID- 27267309 TI - Access to HIV treatment and care for people who inject drugs in Kenya: a short report. AB - People who inject drugs (PWID) experience a range of barriers to HIV treatment and care access. The Kenyan government and community-based organisations have sought to develop HIV care for PWID. A principal approach to delivery in Kenya is to provide care from clinics serving the general population and for this to be linked to support from community-based organisations providing harm reduction outreach. This study explores accounts of PWID accessing care in Kenya to identify care barriers and facilitators. PWID accounts were collected within a qualitative longitudinal study. In-depth interviews with PWID living with HIV (n = 44) are combined with interviews with other PWID, care providers and community observation. Results show that some PWID are able to access care successfully, whilst other PWID report challenges. The results focus on three principal themes to give insights into these experiences: the hardship of addiction and the costs of care, the silencing of HIV in the community and then discrimination and support in the clinic. Some PWID are able to overcome, often with social and outreach support, barriers to clinic access; for others, the challenges of addiction, hardship, stigma and discrimination are too constraining. We discuss how clinics serving the general population could be further adapted to increase access. Clinic-based care, even with community links, may, however, be fundamentally challenging for some PWID to access. Additional strategies to develop stand-alone care for PWID and also decentralise HIV treatment and care to community settings and involve peers in delivery should be considered. PMID- 27267310 TI - Frequency of Hand Decontamination of Intraoperative Providers and Reduction of Postoperative Healthcare-Associated Infections: A Randomized Clinical Trial of a Novel Hand Hygiene System. AB - BACKGROUND Healthcare provider hands are an important source of intraoperative bacterial transmission events associated with postoperative infection development. OBJECTIVE To explore the efficacy of a novel hand hygiene improvement system leveraging provider proximity and individual and group performance feedback in reducing 30-day postoperative healthcare-associated infections via increased provider hourly hand decontamination events. DESIGN Randomized, prospective study. SETTING Dartmouth-Hitchcock Medical Center in New Hampshire and UMass Memorial Medical Center in Massachusetts. PATIENTS Patients undergoing surgery. METHODS Operating room environments were randomly assigned to usual intraoperative hand hygiene or to a personalized, body-worn hand hygiene system. Anesthesia and circulating nurse provider hourly hand decontamination events were continuously monitored and reported. All patients were followed prospectively for the development of 30-day postoperative healthcare-associated infections. RESULTS A total of 3,256 operating room environments and patients (1,620 control and 1,636 treatment) were enrolled. The mean (SD) provider hand decontamination event rate achieved was 4.3 (2.9) events per hour, an approximate 8-fold increase in hand decontamination events above that of conventional wall mounted devices (0.57 events/hour); P<.001. Use of the hand hygiene system was not associated with a reduction in healthcare-associated infections (odds ratio, 1.07 [95% CI, 0.82-1.40], P=.626). CONCLUSIONS The hand hygiene system evaluated in this study increased the frequency of hand decontamination events without reducing 30-day postoperative healthcare-associated infections. Future work is indicated to optimize the efficacy of this hand hygiene improvement strategy. Infect Control Hosp Epidemiol 2016;37:888-895. PMID- 27267312 TI - Formation of Superlattices of Gold Nanoparticles Using Ostwald Ripening in Emulsions: Transition from fcc to bcc Structure. AB - An efficient method to form 3D superlattices of gold nanoparticles inside oil emulsion droplets is presented. We demonstrate that this method relies on Ostwald ripening, a well-known phenomenon occurring during the aging of emulsions. The key point is that the nanoparticle concentration inside the smaller droplets is increasing very slowly with time, thus inducing the crystallization of the nanoparticles into superlattices. Using oil-in-water emulsions doped with hydrophobic gold nanoparticles, we demonstrate that this method is efficient for different types of oils (toluene, cyclohexane, dodecane, and hexadecane). 3D superlattices of the nanoparticles are obtained, with dimensions reaching a hundred nanometers. The kinetics of the crystallization depends on the solubility of the oil in water but also on the initial concentration of the gold nanoparticles in oil. This method also provides an innovative way to obtain the complete phase diagram of nanoparticle suspensions with concentration. Indeed, during this slow crystallization process, a transition from a disordered suspension to a fcc structure is observed, followed by a transition toward a bcc structure. This evolution with time provides key results to understand the role played by the ligands located at the surface of the nanoparticles in order to control the type of superlattices which are formed. PMID- 27267311 TI - Epilepsy in KCNH1-related syndromes. AB - KCNH1 mutations have been identified in patients with Zimmermann-Laband syndrome and Temple-Baraitser syndrome, as well as patients with uncharacterized syndromes with intellectual disability and overlapping features. These syndromes include dysmorphic facial features, nail hypo/aplasia, thumb and skeletal anomalies, intellectual disability, and seizures. We report the epilepsy phenotype in patients with KCNH1 mutations. Demographic data, electroclinical features, response to antiepileptic drugs, and results of significant diagnostic investigations of nine patients carrying mutations in KCNH1 were obtained from referring centres. Epilepsy was present in 7/9 patients. Both generalized and focal tonic-clonic seizures were observed. Complete seizure control was achieved with pharmacological treatment in 2/7 patients; polytherapy was required in 4/7 patients. Status epilepticus occurred in 4/7 patients. EEG showed a diffusely slow background in 7/7 patients with epilepsy, with variable epileptiform abnormalities. Cerebral folate deficiency and an increase in urinary hypoxanthine and uridine were observed in one patient. Epilepsy is a key phenotypic feature in most individuals with KCNH1-related syndromes, suggesting a direct role of KCNH1 in epileptogenesis, although the underlying mechanism is not understood. PMID- 27267313 TI - Olanzapine for Nausea, Delirium, Anxiety, Insomnia, and Cachexia #315. PMID- 27267314 TI - Diabetes knowledge among Greek Type 2 Diabetes Mellitus patients. AB - BACKGROUND & OBJECTIVE: Diabetes knowledge has been shown to improve glycemic control and associate with several demographic parameters. In Greece, a country with high obesity rates, disease knowledge has never been evaluated in diabetic patients. This cross sectional study aimed to assess diabetes knowledge and its associations between social and demographic parameters, among Greek type 2 diabetes mellitus (T2DM) patients. METHODS: One hundred fifty nine patients with T2DM were recruited from an urban and a rural clinic in Greece. Diabetes knowledge was assessed with the Brief Diabetes Knowledge Test (DKT). Basic anthropometry was performed. Data regarding glycemic control and sociodemographic characteristics were collected from the patients' medical files. RESULTS: Greek T2DM patients demonstrated poor disease knowledge (mean DKT score 8.3+/-2.2/14.0 and mean DKT as a percent of correct answers 59.6+/-15.8%). No differences were observed between sex, place of residence, or glycemic control, among subjects. Patients with higher education demonstrated greater diabetes knowledge. Simple obesity with concurrent central obesity or suboptimal glycemic control decreased diabetes knowledge among participants. Additionally, waist circumference was inversely correlated to diabetes knowledge. CONCLUSIONS: Based on the DKT, Greek patients exhibit poor diabetes knowledge. This study provides evidence for the need for better diabetes education in order to ameliorate disease outcome. PMID- 27267315 TI - Thyroid dysfunction in the era of precision medicine. AB - The launching of the Precision Medicine Initiative by the President of the United States in January 2015 was an invitation for all healthcare professionals to review their practice. This call should stimulate thyroidologists working in different areas (from basic research or epidemiology to the frontline of the clinical arena or to those designing public health programs) to be aware of this new outlook. The aim of the initiative is to eradicate imprecision in estimating the probability of a correct diagnosis, to be as sure as possible of the most effective treatment, and to maximize the chances of a successful outcome. This paper summarizes some of the current challenges faced by endocrinologists in the field of thyroid dysfunction, and illustrates how precision medicine may improve diagnosis and therapy in the future. PMID- 27267316 TI - Encapsulated, High-Performance, Stretchable Array of Stacked Planar Micro Supercapacitors as Waterproof Wearable Energy Storage Devices. AB - We report the fabrication of an encapsulated, high-performance, stretchable array of stacked planar micro-supercapacitors (MSCs) as a wearable energy storage device for waterproof applications. A pair of planar all-solid-state MSCs with spray-coated multiwalled carbon nanotube electrodes and a drop-cast UV patternable ion-gel electrolyte was fabricated on a polyethylene terephthalate film using serial connection to increase the operation voltage of the MSC. Additionally, multiple MSCs could be vertically stacked with parallel connections to increase both the total capacitance and the areal capacitance owing to the use of a solid-state patterned electrolyte. The overall device of five parallel connected stacked MSCs, a microlight-emitting diode (MU-LED), and a switch was encapsulated in thin Ecoflex film so that the capacitance remained at 82% of its initial value even after 4 d in water; the MU-LED was lit without noticeable decrease in brightness under deformation including bending and stretching. Furthermore, an Ecoflex encapsulated oximeter wound around a finger was operated using the stored energy of the MSC array attached to the hand (even in water) to give information on arterial pulse rate and oxygen saturation in the blood. This study suggests potential applications of our encapsulated MSC array in wearable energy storage devices especially in water. PMID- 27267317 TI - Could cannabidiol be used as an alternative to antipsychotics? AB - Schizophrenia is a mental disorder that affects close to 1% of the population. Individuals with this disorder often present signs such as hallucination, anxiety, reduced attention, and social withdrawal. Although antipsychotic drugs remain the cornerstone of schizophrenia treatment, they are associated with severe side effects. Recently, the endocannabinoid system (ECS) has emerged as a potential therapeutic target for pharmacotherapy that is involved in a wide range of disorders, including schizophrenia. Since its discovery, a lot of effort has been devoted to the study of compounds that can modulate its activity for therapeutic purposes. Among them, cannabidiol (CBD), a non-psychoactive component of cannabis, shows great promise for the treatment of psychosis, and is associated with fewer extrapyramidal side effects than conventional antipsychotic drugs. The overarching goal of this review is to provide current available knowledge on the role of the dopamine system and the ECS in schizophrenia, and to discuss key findings from animal studies and clinical trials investigating the antipsychotic potential of CBD. PMID- 27267318 TI - Visual attentional bias for food in adolescents with binge-eating disorder. AB - Evidence suggests that adults with binge-eating disorder (BED) are prone of having their attention interfered by food cues, and that food-related attentional biases are associated with calorie intake and eating disorder psychopathology. For adolescents with BED experimental evidence on attentional processing of food cues is lacking. Using eye-tracking and a visual search task, the present study examined visual orienting and disengagement processes of food in youth with BED. Eye-movement data and reaction times were recorded in 25 adolescents (12-20 years) with BED and 25 controls (CG) individually matched for sex, age, body mass index, and socio-economic status. During a free exploration paradigm, the BED group showed a greater gaze duration bias for food images than the CG. Groups did not differ in gaze direction biases. In a visual search task, the BED group showed a greater detection bias for food targets than the CG. Group differences were more pronounced for personally attractive than unattractive food images. Regarding clinical associations, only in the BED group the gaze duration bias for food was associated with increased hunger and lower body mass index, and the detection bias for food targets was associated with greater reward sensitivity. The study provided first evidence of an attentional bias to food in adolescents with BED. However, more research is needed for further specifying disengagement and orienting processes in adolescent BED, including overt and covert attention, and their prospective associations with binge-eating behaviors and associated psychopathology. PMID- 27267319 TI - Association of the miR-146a rs2910164 polymorphism with gastric cancer susceptibility and prognosis. AB - AIM: Single nucleotide polymorphisms in miRNA-coding region may be involved in the development or progression of gastric cancer (GC). MATERIALS & METHODS: Six SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-27a rs895819, miR-423 rs6505162, miR-608 rs4919510, miR-149 rs2292832) were genotyped in 898 histologically confirmed GC cases and 992 controls in this hospital-based case control study. RESULTS: The G/G genotype of rs2910164 was associated with reduced risk of GC (odds ratio: 0.76, 95% CI: 0.60-0.97; p = 0.024). Meanwhile, in 838 GC cases receiving radical tumorectomy, cases bearing the G/G genotype of rs2910164 had shorter survival time comparing to cases with C/C or C/G genotype (hazard ratio: 1.36, 95% CI: 1.04-1.78, p = 0.023). CONCLUSION: rs2910164 of miR-146a is associated with GC. PMID- 27267320 TI - lncRNA Up-Regulated in Nonmuscle Invasive Bladder Cancer Facilitates Tumor Growth and Acts as a Negative Prognostic Factor of Recurrence. AB - PURPOSE: While lncRNAs (long noncoding RNAs) have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle invasive bladder cancer remain largely unknown. We identified a lncRNA termed lncRNA-UNMIBC (up-regulated in nonmuscle invasive bladder cancer) and evaluated its prognostic value in patients with primary nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We analyzed the expression of lncRNA UNMIBC in the tissues of 75 cases of primary nonmuscle invasive bladder cancer and adjacent normal mucosa by quantitative real-time polymerase chain reaction. Data were compared with clinicopathological parameters using the Kaplan-Meier method and multivariate Cox regression analysis. The functions of lncRNA-UNMIBC were assessed by silencing the lncRNA in vitro and in vivo. RNA immunoprecipitation was performed to assay whether lncRNA-UNMIBC could be physically associated with EZH2 (enhancer of zeste homolog 2) and SUZ12 (SUZ12 polycomb repressive complex 2 subunit), which are core components of PRC2 (polycomb repressive complex 2). Chromatin immunoprecipitation was done to examine histone modification status. RESULTS: The expression level of lncRNA UNMIBC was up-regulated in the tissues of 45 cases of primary nonmuscle invasive bladder cancer compared with normal mucosa. Kaplan-Meier estimates showed that lncRNA-UNMIBC expression was significantly associated with recurrence (log rank test p = 0.0151). We also found that lncRNA-UNMIBC had a key role in G0/G1 arrest. Furthermore, RNA and chromatin immunoprecipitation assays demonstrated that lncRNA-UNMIBC was physically associated with EZH2 and SUZ12, leading to an altered histone H3 lysine 27 methylation status of target genes. CONCLUSIONS: These findings indicate that lncRNA-UNMIBC can facilitate tumor growth and may act as a negative prognostic factor of recurrence. PMID- 27267321 TI - Cell versus Chemokine Therapy in a Nonhuman Primate Model of Chronic Intrinsic Urinary Sphincter Deficiency. AB - PURPOSE: Mixed efficacy results of autologous skeletal muscle precursor cell therapy in women with chronic intrinsic urinary sphincter deficiency have increased interest in the therapeutic value of alternative regenerative medicine approaches. The goal of this study was to compare the effects of the cell homing chemokine CXCL12 (C-X-C motif chemokine 12) and skeletal muscle precursor cells on chronic urinary sphincter regeneration in chronic intrinsic urinary sphincter deficiency. MATERIALS AND METHODS: Five million autologous skeletal muscle precursor cells or 100 ng CXCL12 were injected in the urinary sphincter complex of adult female cynomolgus monkeys with chronic (6-month history) intrinsic urinary sphincter deficiency. These treatment groups of 3 monkeys per group were compared to a group of 3 with no intrinsic urinary sphincter deficiency and no injection, and a group of 3 with intrinsic urinary sphincter deficiency plus vehicle injection. Maximal urethral pressure was measured at rest, during stimulation of the urinary sphincter pudendal nerves at baseline and again 6 months after treatment. The monkeys were then necropsied. The urinary sphincters were collected for tissue analysis of muscle and collagen content, vascularization and motor endplates. RESULTS: CXCL12 but not skeletal muscle precursor cells increased resting maximal urethral pressure in nonhuman primates with chronic intrinsic urinary sphincter deficiency compared to that in monkeys with intrinsic urinary sphincter plus vehicle injection (p >0.05). Skeletal muscle precursor cells and CXCL12 only partially restored pudendal nerve stimulated increases in maximal urethral pressure (p >0.05), sphincter vascularization and motor endplate expression in monkeys with chronic intrinsic urinary sphincter deficiency. Additionally, CXCL12 but not skeletal muscle precursor cell injections decreased collagen and increased the muscle content of urinary sphincter complex in monkeys with chronic intrinsic urinary sphincter deficiency compared to those with intrinsic urinary sphincter plus vehicle injection and no intrinsic urinary sphincter plus no injection (p <0.05 and >0.05, respectively). CONCLUSIONS: These results raise questions about cell therapy for chronic intrinsic urinary sphincter deficiency and identify a chemokine treatment (CXCL12) as a potential alternative treatment of chronic intrinsic urinary sphincter deficiency. PMID- 27267322 TI - Coarse-Grained Simulations of Heme Proteins: Validation and Study of Large Conformational Transitions. AB - Heme proteins are ubiquitous in nature and perform many diverse functions in all kingdoms of life. Many of these functions are related to large-scale conformational transitions and allosteric processes. Sampling of these large conformational changes is computationally very challenging. In this context, coarse-grain simulations emerge as an efficient approach to explore the conformational landscape. In this work, we present a coarse-grained model of the heme group and thoroughly validate this model in different benchmark examples, which include the monomeric heme proteins myoglobin and neuroglobin and the tetrameric human hemoglobin where we evaluated the method's ability to explore conformational changes (as the formation of hexacoordinated species) and allosteric transitions (as the well-known R -> T transition). The obtained results are compared with atomistic molecular dynamics simulations. Overall, the results indicate that this approach conserves the essential dynamical information on different allosteric processes. PMID- 27267323 TI - Subjective socioeconomic status causes aggression: A test of the theory of social deprivation. AB - Seven studies (overall N = 3690) addressed the relation between people's subjective socioeconomic status (SES) and their aggression levels. Based on relative deprivation theory, we proposed that people low in subjective SES would feel at a disadvantage, which in turn would elicit aggressive responses. In 3 correlational studies, subjective SES was negatively related to trait aggression. Importantly, this relation held when controlling for measures that are related to 1 or both subjective SES and trait aggression, such as the dark tetrad and the Big Five. Four experimental studies then demonstrated that participants in a low status condition were more aggressive than were participants in a high status condition. Compared with a medium-SES condition, participants of low subjective SES were more aggressive rather than participants of high subjective SES being less aggressive. Moreover, low SES increased aggressive behavior toward targets that were the source for participants' experience of disadvantage but also toward neutral targets. Sequential mediation analyses suggest that the experience of disadvantage underlies the effect of subjective SES on aggressive affect, whereas aggressive affect was the proximal determinant of aggressive behavior. Taken together, the present research found comprehensive support for key predictions derived from the theory of relative deprivation of how the perception of low SES is related to the person's judgments, emotional reactions, and actions. (PsycINFO Database Record PMID- 27267324 TI - How taking photos increases enjoyment of experiences. AB - Experiences are vital to the lives and well-being of people; hence, understanding the factors that amplify or dampen enjoyment of experiences is important. One such factor is photo-taking, which has gone unexamined by prior research even as it has become ubiquitous. We identify engagement as a relevant process that influences whether photo-taking will increase or decrease enjoyment. Across 3 field and 6 lab experiments, we find that taking photos enhances enjoyment of positive experiences across a range of contexts and methodologies. This occurs when photo-taking increases engagement with the experience, which is less likely when the experience itself is already highly engaging, or when photo-taking interferes with the experience. As further evidence of an engagement-based process, we show that photo-taking directs greater visual attention to aspects of the experience one may want to photograph. Lastly, we also find that this greater engagement due to photo-taking results in worse evaluations of negative experiences. (PsycINFO Database Record PMID- 27267325 TI - Coresidence duration and cues of maternal investment regulate sibling altruism across cultures. AB - Genetic relatedness is a fundamental determinant of social behavior across species. Over the last few decades, researchers have been investigating the proximate psychological mechanisms that enable humans to assess their genetic relatedness to others. Much of this work has focused on identifying cues that predicted relatedness in ancestral environments and examining how they regulate kin-directed behaviors. Despite progress, many basic questions remain unanswered. Here we address three of these questions. First, we examine the replicability of the effect of two association-based cues to relatedness-maternal perinatal association (MPA) and coresidence duration-on sibling-directed altruism. MPA, the observation of a newborn being cared for by one's mother, strongly signals relatedness, but is only available to the older sibling in a sib-pair. Younger siblings, to whom the MPA cue is not available, appear to fall back on the duration of their coresidence with an older sibling. Second, we determine whether the effects of MPA and coresidence duration on sibling-directed altruism obtain across cultures. Last, we explore whether paternal perinatal association (PPA) informs sibship. Data from six studies conducted in California, Hawaii, Dominica, Belgium, and Argentina support past findings regarding the role of MPA and coresidence duration as cues to siblingship. By contrast, PPA had no effect on altruism. We report on levels of altruism toward full, half, and step siblings, and discuss the role alternate cues might play in discriminating among these types of siblings. (PsycINFO Database Record PMID- 27267326 TI - Autoinflammatory syndromes: rare diseases with important implications in quality of life. PMID- 27267327 TI - The correlation between antiphospholipid syndrome and cryoglobulinemia: case series of 4 patients and review of the literature. AB - BACKGROUND: Cryoglobulinemia is an immune-complex-mediated small vessel vasculitis that classically involves the skin, kidneys and peripheral nerves. Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder which causes blood vessel thrombosis. It can present as a multi-organ microthrombotic disorder which is called catastrophic APS. OBJECTIVE: In this case series we aim to describe the diagnostic and management challenges that arise when these two severe disorders simultaneously present in the same patient. METHODS: We describe four patients who were admitted to our hospital due to multi-organ life threatening damage mediated by cryoglobulinemic vasculitis with concurrent APS. RESULTS: Clinical manifestations included leg ulcers, livedo reticularis, renal failure, and peripheral neuropathy. Suggested etiologies for the combined syndromes were hepatitis C, systemic lupus erythematosus and myeloproliferative disease rectal maltoma. All of our patients were treated with anticoagulation, high-dose corticosteroids, rituximab, intravenous gammaglobulins and plasma exchange. CONCLUSION: The rare association of severe or catastrophic APS with cryoglobulinemia in patients should be considered by physicians who treat patients with multi-organ ischemia or necrosis. PMID- 27267328 TI - Analysis of the psychometric properties of the American Orthopaedic Foot and Ankle Society Score (AOFAS) in rheumatoid arthritis patients: application of the Rasch model. AB - OBJECTIVE: To tested the reliability and validity of Aofas in a sample of rheumatoid arthritis patients. METHODS: The scale was applicable to rheumatoid arthritis patients, twice by the interviewer 1 and once by the interviewer 2. The Aofas was subjected to test-retest reliability analysis (with 20 Rheumatoid arthritis subjects). The psychometric properties were investigated using Rasch analysis on 33 Rheumatoid arthritis patients. RESULTS: Intra-Class Correlation Coefficient (ICC) were (0.90=9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis. RESULTS: Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8 32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1 673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar. CONCLUSIONS: HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates. PMID- 27267373 TI - Performance Characteristics of Commercial Immunoassays for the Detection of IgG and IgM Antibodies to beta2 Glycoprotein I and an Initial Assessment of Newly Developed Reference Materials for Assay Calibration. AB - OBJECTIVES: To investigate the performance characteristics and impact of newly developed reference calibrators on the commutability between anti-beta2 glycoprotein I (anti-beta2 GPI) immunoassays in antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE). METHODS: Immunoglobulin G (IgG) and immunoglobulin M (IgM) anti-beta2 GPI immunoassays from four manufacturers were evaluated. Serum samples from 269 patients (APS only, n = 31; SLE and APS, n = 83; SLE only, n = 129; pregnancy-related clinical manifestations without APS, n = 26) and 162 women with histories of successful pregnancies were tested. Results were expressed in kit-specific arbitrary units and in the calibrator reference units (RUs) based on 99th percentile cutoff values. Diagnostic accuracies, correlation between kits, and specific clinical manifestations in APS were investigated. RESULTS: The sensitivities of the assays ranged from 15.8% to 27.2% (IgG) and 12.3% to 15.8% (IgM) while specificities ranged from 79.4% to 86.5% (IgG) and 80.6% to 84.5% (IgM). There was moderate to almost perfect interassay reliability (Cohen kappa, 0.69-0.98), and Spearman correlation coefficients were generally improved when results of the IgG determinations were expressed in RUs. CONCLUSIONS: Although qualitative agreements between immunoassays for both antibody isotypes are acceptable, correlations with APS clinical manifestations were kit dependent. Only the use of IgG reference material improved quantitative correlations between assays. PMID- 27267374 TI - Elevated Cell-Free DNA Measured by a Simple Assay Is Associated With Increased Rate of Colorectal Cancer Relapse. AB - OBJECTIVES: For patients with early stage colorectal cancer (CRC), markers of high-risk relapse are needed. In a previous study on 38 randomly selected patients with CRC, we found good correlation between presurgery cell-free DNA (CFD) concentrations and standard prognostic factors. In the current study, we revisited the same patients at 5-year survival, aiming to evaluate the predictive power of presurgery CFD levels. METHODS: We revisited 38 patients with CRC previously analyzed for 5-year outcome. CFD was measured using a simple fluorescent assay that we developed. RESULTS: All recurrent patients and patients who had died of cancer within 5 years were shown to have presurgery CFD values above 800 ng/mL. The negative predictive value for cancer-related disease was 100%. Cox regression analysis for disease-free survival showed a hazard ratio of 6.03 (P = .003) for CFD, which was higher than the ratio of the disease stage, 1.9 (P = .006). The survival-free curve of stage I and II patients with elevated CFD was significantly different from patients with normal levels (P = .0136); 5 (41.7%) of 12 patients had died of cancer or had experienced a recurrence. CONCLUSIONS: CFD may possibly be a decisive criterion to identify patients with local disease who might benefit from adjuvant chemotherapy. PMID- 27267375 TI - Pathology Consultation on Patients With a Large Rh Immune Globulin Dose Requirement. AB - OBJECTIVES: To review the differential diagnosis and laboratory issues for women with a large calculated dose of Rh immune globulin (RhIG). METHODS: A case-based approach is used to review the differential diagnosis of patients with a large calculated dose of RhIG, RhIG dosing for women with baseline elevations in hemoglobin F, the formulations of RhIG, and issues for the transfusion medicine service with the release of large doses of RhIG. RESULTS: A large fetomaternal bleed after delivery requiring multiple doses of RhIG is rare. Such patients may require intravenous RhIG to avoid multiple injections. Patients with a large percentage of circulating fetal RBCs should be evaluated for a disorder of hemoglobin synthesis and, if present, should have quantification of the circulating fetal RBCs by flow cytometry. CONCLUSIONS: Accurate laboratory evaluation of women with large fetomaternal bleeds is essential for appropriate RhIG administration. PMID- 27267372 TI - Equine rhinitis B viruses in horse fecal samples from the Middle East. AB - BACKGROUND: Among all known picornaviruses, only two species, equine rhinitis A virus and equine rhinitis B virus (ERBV) are known to infect horses, causing respiratory infections. No reports have described the detection of ERBV in fecal samples of horses and no complete genome sequences of ERBV3 are available. METHODS: We performed a molecular epidemiology study to detect ERBVs in horses from Dubai and Hong Kong. Complete genome sequencing of the ERBVs as well as viral loads and genome, phylogenetic and evolutionary analysis were performed on the positive samples. RESULTS: ERBV was detected in four (13.8 %) of the 29 fecal samples in horses from Dubai, with viral loads 8.28 * 10(3) to 5.83 * 10(4) copies per ml, but none of the 47 fecal samples in horses from Hong Kong by RT PCR. Complete genome sequencing and phylogenetic analysis showed that three of the four strains were ERBV3 and one was ERBV2. The major difference between the genomes of ERBV3 and those of ERBV1 and ERBV2 lied in the amino acid sequences of their VP1 proteins. The Ka/Ks ratios of all the coding regions in the ERBV3 genomes were all <0.1, suggesting that ERBV3 were stably evolving in horses. Using the uncorrelated lognormal distributed relaxed clock model on VP1 gene, the date of the most recent common ancestor (MRCA) of ERBV3 was estimated to be 1785 (HPDs, 1176 to 1937) and the MRCA dates of ERBV1 and ERBV2 were estimated to be 1848 (HPDs, 1466 to 1949) respectively. CONCLUSIONS: Both acid stable (ERBV3) and acid labile (ERBV2) ERBVs could be found in fecal samples of horses. Detection of ERBVs in fecal samples would have implications for their transmission and potential role in gastrointestinal diseases as well as fecal sampling as an alternative method of identifying infected horses. PMID- 27267376 TI - Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol. AB - Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels. We first determined the biophysical consequences of epilepsy-associated missense mutations in both Nav1.1 (arginine 1648 to histidine and asparagine 1788 to lysine) and Nav1.6 (asparagine 1768 to aspartic acid and leucine 1331 to valine) by obtaining whole-cell patch clamp recordings in human embryonic kidney 293T cells with 200 MUM Navbeta4 peptide in the pipette solution to induce resurgent sodium currents. Resurgent sodium current is an atypical near threshold current predicted to increase neuronal excitability and has been implicated in multiple disorders of excitability. We found that both mutations in Nav1.6 dramatically increased resurgent currents while mutations in Nav1.1 did not. We then examined the effects of anandamide and cannabidiol on peak transient and resurgent currents from wild-type and mutant channels. Interestingly, we found that cannabidiol can preferentially target resurgent sodium currents over peak transient currents generated by wild-type Nav1.6 as well as the aberrant resurgent and persistent current generated by Nav1.6 mutant channels. To further validate our findings, we examined the effects of cannabidiol on endogenous sodium currents from striatal neurons, and similarly we found an inhibition of resurgent and persistent current by cannabidiol. Moreover, current clamp recordings show that cannabidiol reduces overall action potential firing of striatal neurons. These findings suggest that cannabidiol could be exerting its anticonvulsant effects, at least in part, through its actions on voltage-gated sodium channels, and resurgent current may be a promising therapeutic target for the treatment of epilepsy syndromes. PMID- 27267377 TI - Reply: Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1. PMID- 27267378 TI - Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1. PMID- 27267379 TI - Response to letter to editor titled "Physical restraint in mechanically ventilated adults: A complex early diagnosis by protocols?". PMID- 27267380 TI - Eluxadoline for the treatment of diarrhoea-predominant irritable bowel syndrome. AB - INTRODUCTION: Irritable bowel syndrome (IBS) treatment is challenging physicians because of its multifactorial physiopathology. In particular, abdominal pain and diarrhea management lack one unique effective pharmacological remedy. Opioid receptors, present in the central nervous system (CNS) and the enteric nervous system (ENS), are involved in visceral sensitivity and gastrointestinal motility control. To date only a few opioid receptor modulators are currently in use for the treatment of IBS but with dosage limitations due to the early development of severe constipation. AREAS COVERED: In this drug evaluation manuscript we review the irritable bowel syndrome therapeutic needs and chemistry, pharmacokinetics and -dynamics, clinical study results with the new opioid receptor ligand eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). EXPERT OPINION: Eluxadoline shows a peculiar pharmacological profile with MU-opioid agonism and delta-opioid antagonism actions. Its efficacy over placebo for the treatment of abdominal pain and diarrhea in IBS-D has been demonstrated in short- and long-term clinical studies in humans. Its safety has been evaluated in the same studies. Interestingly, eluxadoline showed a low rate of constipation development in IBS patients in comparison with known effects of other opioid receptor modulators. Patients with a history of acute pancreatitis should not be treated with eluxadoline. PMID- 27267381 TI - WITHDRAWN: Use of Repositionable Transcatheter Aortic Valve Systems in Past Mechanical Prosthetic Mitral Valve Recipients. AB - This article has been withdrawn, at the request of the Editor, due to the absence of the corresponding permissions for use of all the data/images. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 27267382 TI - Chronic Ischemic Heart Disease in the Elderly. Consensus Document of the Spanish Societies of Cardiology, Internal Medicine, Primary Care, and Geriatrics. PMID- 27267383 TI - Effects of Excimer Laser Coronary Atherectomy Assessed by OCT. PMID- 27267384 TI - Update on the imaging diagnosis of otosclerosis. AB - Otosclerosis is a primary osteodystrophy of the temporal bone that causes progressive conductive hearing loss. The diagnosis is generally clinical, but multidetector CT (MDCT), the imaging technique of choice, is sometimes necessary. The objective of this article is to systematically review the usefulness of imaging techniques for the diagnosis and postsurgical assessment of otosclerosis, fundamentally the role of MDCT, to decrease the surgical risk. PMID- 27267385 TI - Biological Maturation, Central Adiposity, and Metabolic Risk in Adolescents: A Mediation Analysis. AB - BACKGROUND: Earlier biological maturation has been related to increased metabolic risk. In this study, we verified mediating effects by central adiposity of the relationship between somatic maturity and metabolic risk factors in adolescents. METHODS: In a cross-sectional study, 1034 adolescents aged 10-16 years from Londrina/PR/Brazil were evaluated. The age of peak height velocity (PHV) method was used to evaluate somatic maturity. Central adiposity was estimated through waist circumference measurements. Fasting glucose, triglycerides, high-density lipoprotein cholesterol (HDL-C), and blood pressure were measured as metabolic risk indicators. Physical activity (Baecke questionnaire) and cardiorespiratory fitness (20-m shuttle run test) were used as covariates. RESULTS: Except for fasting glucose, waist circumference showed partial or full mediation of the relationship between maturity and the following metabolic risk factors with their respective z-score values: triglycerides (boys = -3.554 vs. girls = -5.031), HDL C (boys = +5.300 vs. girls = +5.905), systolic blood pressure (boys = -3.540 vs. girls = -3.763), diastolic blood pressure (boys = -2.967 vs. girls = -3.264), and metabolic risk score (boys = -5.339 vs. girls = -6.362). CONCLUSIONS: The results suggest that central obesity plays a mediating role in the relationship between somatic maturation and metabolic risk during adolescence. PMID- 27267387 TI - Surviving brain damage after assault: from vegetative state to meaningful life. PMID- 27267386 TI - cAMP-specific PDE4 phosphodiesterases and AIP in the pathogenesis of pituitary tumors. AB - PDE4 cyclic nucleotide phosphodiesterases regulate cAMP abundance in cells and therefore regulate numerous processes, including cell growth and differentiation. The rat PDE4A5 isoform (human homolog PDE4A4) interacts with the AIP protein (also called XAP2 or ARA-9). Germline mutations in AIP occur in approximately 20% of patients with Familial Isolated Pituitary Adenoma (FIPA) and 20% of childhood onset simplex somatotroph adenomas. We therefore examined the protein expression of PDE4A4 and the closely related isoform PDE4A8 in normal human pituitary tissue and in pituitary adenomas. PDE4A4 had low expression in normal pituitary but was significantly overexpressed in somatotroph, lactotroph, corticotroph and clinically nonfunctioning gonadotroph adenomas (P<0.0001 for all subtypes). Likewise, PDE4A8 was expressed in normal pituitary and was also significantly overexpressed in the adenoma subtypes (P<0.0001 for all). Among the different adenoma subtypes, corticotroph and lactotroph adenomas were the highest and lowest expressed for PDE4A4, respectively, whereas the opposite was observed for PDE4A8. Naturally occurring oncogenic variants in AIP were shown by a two-hybrid assay to disrupt the ability of AIP to interact with PDE4A5. A reverse two-hybrid screen identified numerous additional variants in the tetratricopeptide repeat (TPR) region of AIP that also disrupted its ability to interact with PDE4A5. The expression of PDE4A4 and PDE4A8 in normal pituitary, their increased expression in adenomatous pituitary cells where AIP is meant to participate, and the disruption of the PDE4A4-AIP interaction by AIP mutants may play a role in pituitary tumorigenesis. PMID- 27267388 TI - Quantitative fetal fibronectin and cervical length to predict preterm birth in asymptomatic women with previous cervical surgery. AB - BACKGROUND: Quantitative fetal fibronectin testing has demonstrated accuracy for prediction of spontaneous preterm birth in asymptomatic women with a history of preterm birth. Predictive accuracy in women with previous cervical surgery (a potentially different risk mechanism) is not known. OBJECTIVE: We sought to compare the predictive accuracy of cervicovaginal fluid quantitative fetal fibronectin and cervical length testing in asymptomatic women with previous cervical surgery to that in women with 1 previous preterm birth. STUDY DESIGN: We conducted a prospective blinded secondary analysis of a larger observational study of cervicovaginal fluid quantitative fetal fibronectin concentration in asymptomatic women measured with a Hologic 10Q system (Hologic, Marlborough, MA). Prediction of spontaneous preterm birth (<30, <34, and <37 weeks) with cervicovaginal fluid quantitative fetal fibronectin concentration in primiparous women who had undergone at least 1 invasive cervical procedure (n = 473) was compared with prediction in women who had previous spontaneous preterm birth, preterm prelabor rupture of membranes, or late miscarriage (n = 821). Relationship with cervical length was explored. RESULTS: The rate of spontaneous preterm birth <34 weeks in the cervical surgery group was 3% compared with 9% in previous spontaneous preterm birth group. Receiver operating characteristic curves comparing quantitative fetal fibronectin for prediction at all 3 gestational end points were comparable between the cervical surgery and previous spontaneous preterm birth groups (34 weeks: area under the curve, 0.78 [95% confidence interval 0.64-0.93] vs 0.71 [95% confidence interval 0.64-0.78]; P = .39). Prediction of spontaneous preterm birth using cervical length compared with quantitative fetal fibronectin for prediction of preterm birth <34 weeks of gestation offered similar prediction (area under the curve, 0.88 [95% confidence interval 0.79-0.96] vs 0.77 [95% confidence interval 0.62-0.92], P = .12 in the cervical surgery group; and 0.77 [95% confidence interval 0.70-0.84] vs 0.74 [95% confidence interval 0.67-0.81], P = .32 in the previous spontaneous preterm birth group). CONCLUSION: Prediction of spontaneous preterm birth using cervicovaginal fluid quantitative fetal fibronectin in asymptomatic women with cervical surgery is valid, and has comparative accuracy to that in women with a history of spontaneous preterm birth. PMID- 27267389 TI - Dietary pollutants induce oxidative stress, altering maternal antioxidant provisioning and reproductive output in the temperate sea urchin Evechinus chloroticus. AB - Evidence is growing to suggest that the capacity to withstand oxidative stress may play an important role in shaping life-history trade-offs, although little is known on the relationship in broadcast spawning marine invertebrates. In this group, variation in gamete quantity and quality are important drivers of offspring survival and successful recruitment. Therefore the provisioning of eggs with antioxidants may be an important driver of life history strategies because they play a critical role in preventing damage from reactive oxygen species to macromolecules. In this study, a suite of oxidative stress biomarkers was measured in the gonads and eggs of the sea urchin Evechinus chloroticus exposed to polycyclic aromatic hydrocarbons (PAHs). Links between oxidative stress markers and core components of fitness including fecundity, gamete quality and maternal transfer of antioxidants were assessed. Experimental induction of oxidative stress was achieved via exposure to a mix of four PAHs over a 21-day period. In PAH exposed individuals, we observed a significant upregulation of the antioxidant defence and detoxification enzymes SOD, CAT, GR, GPx and GST, as well as a greater pool of the non-enzymatic antioxidant glutathione in gonad tissue and eggs. In contrast, glutathione redox status was not affected by PAH exposure, with the percentage of reduced glutathione remaining at approximately 80% in both gonad tissue and released eggs. PAH-exposed adults experienced greater than three and five-fold increases in oxidative protein and lipid damage, respectively, in gonad tissue. In contrast, eggs maintained low levels of damage, not differing from baseline levels found in eggs released from PAH-naive mothers. PAH exposure also resulted in a 2-fold reduction in fecundity of reproductively mature females but no significant alteration to egg diameter. Although PAH-exposed females released fewer eggs, successful fertilisation of those eggs was slightly enhanced with average rates ranging from 90-99% in comparison to 76-90% in control eggs. Early-stage offspring reflected maternal antioxidant status with populations derived from PAH-exposed mothers demonstrating significantly higher antioxidant levels than those derived from PAH-naive mothers. This maternally inherited protection enhanced the capacity of embryos to minimise oxidative damage to lipids and proteins during early development but, despite this, did not reduce the proportion of morphological abnormalities in the population. Overall, these findings indicate that when faced with short-term contaminant stress E. chloroticus has the capacity to trade high reproductive output during a spawning event for a greater antioxidant investment in eggs. However, this production of potentially more resilient offspring did not translate to a fitness gain, at least for the early larval stages in the present experimental conditions. PMID- 27267390 TI - Accumulation and detoxication responses of the gastropod Lymnaea stagnalis to single and combined exposures to natural (cyanobacteria) and anthropogenic (the herbicide RoundUp((r)) Flash) stressors. AB - Freshwater gastropods are increasingly exposed to multiple stressors in the field such as the herbicide glyphosate in Roundup formulations and cyanobacterial blooms either producing or not producing microcystins (MCs), potentially leading to interacting effects. Here, the responses of Lymnaea stagnalis to a 21-day exposure to non-MC or MC-producing (33MUgL(-1)) Planktothrix agardhii alone or in combination with the commercial formulation RoundUp((r)) Flash at a concentration of 1MUgL(-1) glyphosate, followed by 14days of depuration, were studied via i) accumulation of free and bound MCs in tissues, and ii) activities of anti-oxidant (catalase CAT) and biotransformation (glutathione-S-transferase GST) enzymes. During the intoxication, the cyanobacterial exposure induced an early increase of CAT activity, independently of the MC content, probably related to the production of secondary cyanobacterial metabolites. The GST activity was induced by RoundUp((r)) Flash alone or in combination with non MC-producing cyanobacteria, but was inhibited by MC-producing cyanobacteria with or without RoundUp((r)) Flash. Moreover, MC accumulation in L. stagnalis was 3.2 times increased when snails were concomitantly exposed to MC-producing cyanobacteria with RoundUp((r)), suggesting interacting effects of MCs on biotransformation processes. The potent inhibition of detoxication systems by MCs and RoundUp((r)) Flash was reversible during the depuration, during which CAT and GST activities were significantly higher in snails previously exposed to MC-producing cyanobacteria with or without RoundUp((r)) Flash than in other conditions, probably related to the oxidative stress caused by accumulated MCs remaining in tissues. PMID- 27267391 TI - Assessment of gold nanoparticle effects in a marine teleost (Sparus aurata) using molecular and biochemical biomarkers. AB - Gold nanoparticles (AuNP) are increasingly employed in a variety of applications and are likely to be increasing in the environment, posing a potential emerging environmental threat. Information on possible hazardous effects of engineered nanoparticles is urgently required to ensure human and environmental safety and promote the safe use of novel nanotechnologies. Nevertheless, there is a lack of comprehensive knowledge on AuNP effects in marine species. The present study aimed to assess AuNP effects in a marine teleost, Sparus aurata, by combining endpoints at different biological levels (molecular and biochemical). For that purpose, fish were exposed via water for 96h to 4, 80 and 1600MUgL(-1) of AuNP (~40nm) coated with citrate or polyvinylpyrrolidone (PVP). Results revealed a significant impact of AuNP-PVP in the hepatic expression of antioxidant, immune and apoptosis related genes. Total oxidative status was increased in plasma after exposure to the lowest concentration of AuNP-PVP, although without altering the total antioxidant capacity. Furthermore, AuNP did not induce significant damage in the liver since the activity of neither hepatic indicator (aspartate aminotransferase and alkaline phosphatase) increased. Overall, the present study demonstrated that AuNP, even with a biocompatible coating is able to alter oxidative status and expression of relevant target genes in marine fish. Another important finding is that effects are mainly induced by the lowest and intermediate concentrations of the PVP coated AuNP revealing the importance of different coatings. PMID- 27267402 TI - Acute neuromuscular and performance responses to Nordic hamstring exercises completed before or after football training. AB - The optimal scheduling of Nordic Hamstring exercises (NHEs) relative to football training sessions is unknown. We examined the acute neuromuscular and performance responses to NHE undertaken either before (BT) or after (AT) simulated football training. Twelve amateur players performed six sets of five repetitions of the NHE either before or after 60 min of standardised football-specific exercise (SAFT60). Surface electromyography signals (EMG) of the hamstring muscles were recorded during both the NHE, and maximum eccentric actions of the knee flexors (0.52 rad . s-1) performed before and after the NHE programme, and at 15 min intervals during SAFT60. Ten-metre sprint times were recorded on three occasions during each 15 min SAFT60 segment. Greater eccentric hamstring fatigue following the NHE programme was observed in BT versus AT (19.8 %; very likely small effect), which was particularly apparent in the latter range of knee flexion (0 15 degrees ; 39.6%; likely moderate effect), and synonymous with hamstring EMG declines (likely small-likely moderate effects). Performing NHE BT attenuated sprint performance declines (2.0-3.2%; likely small effects), but decreased eccentric hamstring peak torque (-14.1 to -18.9%; likely small effects) during football-specific exercise. Performing NHE prior to football training reduces eccentric hamstring strength and may exacerbate hamstring injury risk. PMID- 27267403 TI - Association of DDX58 177 C > T polymorphism with decreased risk of Epstein-Barr virus-related nodular sclerosis classical Hodgkin lymphoma. AB - Classical Hodgkin lymphoma (cHL) is frequently related to Epstein-Barr virus (EBV) infection. Its malignant capacity is attributed to disruption of an EBV host balance influenced by environmental and genetic drivers. EBV structures activate Type I interferon (IFN) pathway of the innate immunity, therefore, genetic polymorphisms could influence this response. We explored the impact of four single nucleotide polymorphisms (SNPs) on EBV-associated cHL susceptibility. Toll-like receptors 9 (TLR9_rs5743836), and 3 (TLR3_rs3775291), Interleukin-28B (IL28B_rs12979860), and DEAD-box polypeptide 58 (DDX58_rs10813831) were genotyped in 73 EBV-positive and 106 EBV-negative cHL patients and 396 controls. Only DDX58_rs10813831 T-allele was decreased among EBV-positive cHL compared to controls. A stratified analysis in EBV-positive cHL showed that the reduced rate was associated with younger age and nodular sclerosis. In conclusion, DDX58_rs10813831 T-allele may be associated with a reduced risk of nodular sclerosis EBV-related cHL, which suggests a role for RIG-I (retinoic acid inducible gene I), encoded by DDX58, in these cases. PMID- 27267404 TI - Identification mouse patatin-like phospholipase domain containing protein 1 as a skin-specific and membrane-associated protein. AB - Patatin-like phospholipase domain containing protein 1 (PNPLA1) mutations have been identified to be associated with autosomal recessive congenital ichthyosis (ARCI) in recent years. However, its molecular characters have not been achieved until now. In the current study, the full length coding cDNA sequence of mouse PNPLA1 (mPNPLA1) was identified firstly. There were several putative transmembrane domains (TMDs) in mPNPLA1 by bioinformation analysis. mPNPLA1 was further found to be expressed exclusively in the membrane fraction in mammalian cells. However, it did not colocalized with the endoplasmic reticulum (ER) or lipid droplets (LDs). Moreover, the mRNA levels of mPNPLA1 was detected to be highly expressed in the skin, while very weak or even less in other mouse tissues by quantitative PCR. In addition, based on experiments with inhibitors and inducer of protein degradation pathways, mPNPLA1 was demonstrated to be degraded by macroautophagy, but not by the proteasome. These results indicated PNPLA1 was a skin-specific and membrane-associated protein for the first time, suggesting that it may mainly play a role in the skin. PMID- 27267401 TI - Chemical Tools for Dissecting the Role of lncRNAs in Epigenetic Regulation. AB - Proper control and maintenance of gene expression is critical for cellular identity and maintenance. Transcription of RNA from the genome is intimately controlled by post-translational chemical modification of histone tails and DNA. Recent studies have demonstrated that chromatin-remodeling complexes seek out their target genomic loci through the help of noncoding RNA molecules. Within this Review, we will outline how the use of biochemical techniques has shed light on the mechanisms employed by RNA to guide these complexes and therefore control gene expression. PMID- 27267405 TI - Detection of piRNAs in whitespotted bamboo shark liver. AB - Piwi-interacting RNAs (piRNAs) are 26 to 31-nt small non-coding RNAs that have been reported mostly in germ-line cells and cancer cells. However, the presence of piRNAs in the whitespotted bamboo shark liver has not yet been reported. In a previous study of microRNAs in shark liver, some piRNAs were detected from small RNAs sequenced by Solexa technology. A total of 4857 piRNAs were predicted and found in shark liver. We further selected 17 piRNAs with high and significantly differential expression between normal and regenerative liver tissues for subsequent verification by Northern blotting. Ten piRNAs were further identified, and six of these were matched to known piRNAs in piRNABank. The actual expression of six known and four novel piRNAs was validated by qRT-PCR. In addition, a total of 401 target genes of the 10 piRNAs were predicted by miRanda. Through GO and pathway function analyses, only five piRNAs could be annotated with eighteen GO annotations. The results indicated that the identified piRNAs are involved in many important biological responses, including immune inflammation, cell-specific differentiation and development, and angiogenesis. This manuscript provides the first identification of piRNAs in the liver of whitespotted bamboo shark using Solexa technology as well as further elucidation of the regulatory role of piRNAs in whitespotted bamboo shark liver. These findings may provide a useful resource and may facilitate the development of therapeutic strategies against liver damage. PMID- 27267406 TI - Cloning and expression of retinoblastoma-binding protein 4 gene in embryo diapause termination and in response to salinity stress from brine shrimp Artemia sinica. AB - Retinoblastoma binding protein 4 (RBBP4) is a nuclear protein with four WD-repeat sequences and thus belongs to a highly conserved subfamily of proteins with such domains. This retinoblastoma-binding protein plays an important role in nucleosome assembly and histone modification, which influences gene transcription and regulates cell cycle and proliferation. Artemia sinica (brine shrimp) undergoes an unusual diapause process under stress conditions of high salinity and low temperature. However, the role of RBBP4 in diapause termination of embryo development in A. sinica remains unknown. Here, the full-length cDNA of the As rbbp4 gene was obtained from A. sinica and found to contain 1411 nucleotides, including a 1281 bp open reading frame (ORF), 63 bp 5'-untranslated region (UTR) and a 67-bp 3'-UTR, which encodes a 427 amino acid (48 kDa) protein. Bioinformatic analysis indicated As-RBBP4 to be mainly located in the nucleus, with a theoretical isoelectric point of 4.79. Protein sequence domain analysis showed that As-RBBP4 is a conserved protein, especially in the WD40 domain. No specificity in expression of this gene was observed in tissues or organs by in situ hybridization. Real-time quantitative PCR and Western blot analyses of As RBBP4 gene and protein expression, respectively, showed notably high levels at 10 h and a subsequent downward trend. Obvious trends in upregulation of As-RBBP4 were observed under conditions of low temperature and high salinity stress. As E2F1 and As-CyclinE also presented similar trends as that of As-RBBP4 in Western blots. Analysis of the RBBP4 expression in early embryonic development of A. sinica indicated that this protein plays an important role in diapause termination and cell cycle regulation. PMID- 27267407 TI - Annual Zebrafish Husbandry Workshop USA: A Resource for All Zebrafish Users. AB - Understandably, in the early years of the growth of the zebrafish model, husbandry parameters varied widely from laboratory to laboratory. But with the explosion in the number of investigators opting to utilize zebrafish in their research, the standardization of husbandry parameters is not only practical but also absolutely critical to ensure the reliability and reproducibility of experimental results. For more than 13 years, technicians, veterinarians, laboratory managers, regulatory officers, and investigators have joined together for an annual workshop on zebrafish husbandry. The meeting is held in conjunction with the World Aquaculture Society's annual conference, a congeries of fish experts and aquatic species enthusiasts. From a lineup of five speakers and perhaps 25 attendees, the workshop has grown to a one and a half day event with more than 20 speakers and ~90 attendees. PMID- 27267408 TI - Heterologous biosynthesis and manipulation of alkanes in Escherichia coli. AB - Biosynthesis of alkanes in microbial foundries offers a sustainable and green supplement to traditional fossil fuels. The dynamic equilibrium of fatty aldehydes, key intermediates, played a critical role in microbial alkanes production, due to the poor catalytic capability of aldehyde deformylating oxygenase (ADO). In our study, exploration of competitive pathway together with multi-modular optimization was utilized to improve fatty aldehydes balance and consequently enhance alkanes formation in Escherichia coli. Endogenous fatty alcohol formation was supposed to be competitive with alkane production, since both of the two routes consumed the same intermediate-fatty aldehyde. Nevertheless, in our case, alkanes production in E. coli was enhanced from trace amount to 58.8mg/L by the facilitation of moderate fatty alcohol biosynthesis, which was validated by deletion of endogenous aldehyde reductase (AHR), overexpression of fatty alcohol oxidase (FAO) and consequent transcriptional assay of aar, ado and adhP genes. Moreover, alkanes production was further improved to 81.8mg/L, 86.6mg/L or 101.7mg/L by manipulation of fatty acid biosynthesis, lipids degradation or electron transfer system modules, which directly referenced to fatty aldehydes dynamic pools. A titer of 1.31g/L alkanes was achieved in 2.5L fed-batch fermentation, which was the highest reported titer in E. coli. Our research has offered a reference for chemical overproduction in microbial cell factories facilitated by exploring competitive pathway. PMID- 27267410 TI - Gene Therapy Briefs. PMID- 27267409 TI - Optimal tracers for parallel labeling experiments and 13C metabolic flux analysis: A new precision and synergy scoring system. AB - 13C-Metabolic flux analysis (13C-MFA) is a widely used approach in metabolic engineering for quantifying intracellular metabolic fluxes. The precision of fluxes determined by 13C-MFA depends largely on the choice of isotopic tracers and the specific set of labeling measurements. A recent advance in the field is the use of parallel labeling experiments for improved flux precision and accuracy. However, as of today, no systemic methods exist for identifying optimal tracers for parallel labeling experiments. In this contribution, we have addressed this problem by introducing a new scoring system and evaluating thousands of different isotopic tracer schemes. Based on this extensive analysis we have identified optimal tracers for 13C-MFA. The best single tracers were doubly 13C-labeled glucose tracers, including [1,6-13C]glucose, [5,6-13C]glucose and [1,2-13C]glucose, which consistently produced the highest flux precision independent of the metabolic flux map (here, 100 random flux maps were evaluated). Moreover, we demonstrate that pure glucose tracers perform better overall than mixtures of glucose tracers. For parallel labeling experiments the optimal isotopic tracers were [1,6-13C]glucose and [1,2-13C]glucose. Combined analysis of [1,6-13C]glucose and [1,2-13C]glucose labeling data improved the flux precision score by nearly 20-fold compared to widely use tracer mixture 80% [1 13C]glucose +20% [U-13C]glucose. PMID- 27267411 TI - Lower Extremity Kinematic Profile of Gait of Patients After Ankle Fracture: A Case-Control Study. AB - The present study examined the differences in the lower extremity gait kinematic profile of patients recovering from ankle fracture compared with healthy controls. In addition, we inquired whether the profile would differ among fracture severity groups. A total of 48 patients participated in the present prospective, case-control study. The gait of 24 patients recovering from an ankle fracture injury and 24 healthy matched controls was examined using an inertial measurement unit sensor system. The following gait parameters were evaluated: knee range of motion (ROM) during the swing phase, maximum knee flexion angle during stance, thigh and calf ROM, and stride duration. Statistically significant differences were found between the ankle fracture group and the control group for all parameters. The patients with ankle fracture had a lower knee ROM during swing phase compared with the control group (mean +/- standard deviation 43.0 degrees +/- 15.5 degrees compared with 66.7 degrees +/- 5.1 degrees , respectively; p < .001). The maximum knee flexion angle during stance was lower in the patients with ankle fracture than in the control group (mean +/- standard deviation 10.5 degrees +/- 6.1 degrees compared with 21.2 degrees +/- 4.5 degrees , respectively; p < .001). Patients with ankle fracture also had lower gait cycle thigh and calf ROM angles (p < .001) and a longer stride duration (p < .001) compared with the control group. No statistically significant differences were found among the severity groups. These results suggest that the gait kinematic characteristics vary between healthy people and patients recovering from an ankle fracture injury during the short-term period after injury. PMID- 27267412 TI - Functional Outcomes After Temporary Bridging With Locking Plates in Lisfranc Injuries. AB - The standard operative treatment of Lisfranc fracture dislocations currently consists of open reduction and transarticular fixation. Recently, bridge plating has been used more often. Using joint spanning, the reduced fracture dislocation is temporary stabilized to minimize articular damage. The present study describes the outcomes of patients treated with bridge plating after tarsometatarsal fracture dislocations compared with transarticular screw fixation. A retrospective cohort study was performed. Patients with an isolated tarsometatarsal injury who had been treated operatively from June 2000 to October 2013 were included. The primary functional outcome was measured using the American Orthopaedic Foot and Ankle Society midfoot score and the Foot Function Index. The secondary outcome was patient satisfaction, which was measured using the EuroQol 5 dimensions questionnaire and a visual analog scale. A total of 34 patients were included. Bridge plating was used in 21 patients. In 13 patients, Kirschner wires or transarticular screws or a combination were used. The median follow-up period was 49 (interquartile range 18 to 89) months. The implants were removed in 10 of 13 patients in the transarticular group and 17 of 21 patients in the bridge plating group. The incidence of wound complications was comparable in both groups. The median American Orthopaedic Foot and Ankle Society score was lower in the transarticular group (77 versus 66). The Foot Function Index score was 18 in both groups. Patient satisfaction was 90% in the bridge plating group and 80% in the transarticular group. Bridge plating for Lisfranc injuries led to at least similar results compared with transarticular fixation in terms of functional outcomes and patient satisfaction. Longer follow-up is necessary to determine whether the prevention of secondary damage to the articular surface leads to less post-traumatic arthritis and better functional outcomes. PMID- 27267413 TI - Ultrasound-Guided Therapy for Knee and Foot Ganglion Cysts. AB - The present study evaluated the effectiveness of ultrasound-guided aspiration/injection of ganglion cysts in the lower extremities (knee and foot) that required referral to the radiology department for precise localization. The present study is the first series to describe such results. The study population consisted of 15 patients who had undergone treatment from April 2012 to January 2015. Follow-up was by telephone survey, which was performed at a mean of 15 +/- 6 months after treatment. Almost 90% of patients experienced immediate improvement in symptoms (mostly pain), and 77% of these patients had not experienced a recurrence of symptoms at a mean follow-up time of 14 +/- 6 months. In conclusion, ultrasound-guided therapy is a safe and potentially effective treatment for most cases of symptomatic lower extremity ganglion cysts. PMID- 27267415 TI - Anthracene-terpyridine metal complexes as new G-quadruplex DNA binders. AB - The formation of quadruple-stranded DNA induced by planar metal complexes has particular interest in the development of novel anticancer drugs. This is especially relevant for the inhibition of telomerase, which plays an essential role in cancer cell immortalization and is overexpressed in ca. 85-90% of cancer cells. Moreover, G-quadruplexes also exist in other locations in the human genome, namely oncogene promoter regions, and it has been hypothesized that they play a regulatory role in gene transcription. Herein we report a series of new anthracene-containing terpyridine ligands and the corresponding Cu(II) and Pt(II) complexes, with different linkers between the anthracenyl moiety and the terpyridine chelating unit. The interaction of these ligands and metal complexes with different topologies of DNA was studied by several biophysical techniques. The Pt(II) and Cu(II) complexes tested showed affinity for quadruplex-forming sequences with a good selectivity over duplex DNA. Importantly, the free ligands do not have significant affinity for any of the DNA sequences used, which shows that the presence of the metal is essential for high affinity (and selectivity). This effect is more evident in the case of the Pt(II) complexes. Moreover, the presence of a longer linker between the chelating terpyridine unit and the anthracene moiety enhances the interaction with G-quadruplex-forming sequences. We further evaluated the ability of the Cu(II) complexes to interact with, and stabilize G-quadruplex containing regions in oncogene promoters via a polymerase stop assay. These studies indicated that the metal complexes are able to induce G quadruplex formation and stop polymerase activity. PMID- 27267414 TI - Insights into the transcriptional and translational mechanisms of linear organellar chromosomes in the box jellyfish Alatina alata (Cnidaria: Medusozoa: Cubozoa). AB - BACKGROUND: In most animals, the mitochondrial genome is characterized by its small size, organization into a single circular molecule, and a relative conservation of the number of encoded genes. In box jellyfish (Cubozoa, Cnidaria), the mitochondrial genome is organized into 8 linear mito-chromosomes harboring between one and 4 genes each, including 2 extra protein-coding genes: mt-polB and orf314. Such an organization challenges the traditional view of mitochondrial DNA (mtDNA) expression in animals. In this study, we investigate the pattern of mitochondrial gene expression in the box jellyfish Alatina alata, as well as several key nuclear-encoded molecular pathways involved in the processing of mitochondrial gene transcription. RESULTS: Read coverage of DNA-seq data is relatively uniform for all 8 mito-chromosomes, suggesting that each mito chromosome is present in equimolar proportion in the mitochondrion. Comparison of DNA and RNA-seq based assemblies indicates that mito-chromosomes are transcribed into individual transcripts in which the beginning and ending are highly conserved. Expression levels for mt-polB and orf314 are similar to those of other mitochondrial-encoded genes, which provides further evidence for them having functional roles in the mitochondrion. Survey of the transcriptome suggests recognition of the mitochondrial tRNA-Met by the cytoplasmic aminoacyl-tRNA synthetase counterpart and C-to-U editing of the cytoplasmic tRNA-Trp after import into the mitochondrion. Moreover, several mitochondrial ribosomal proteins appear to be lost. CONCLUSIONS: This study represents the first survey of mitochondrial gene expression of the linear multi-chromosomal mtDNA in box jellyfish (Cubozoa). Future exploration of small RNAs and the proteome of the mitochondrion will test the hypotheses presented herein. PMID- 27267420 TI - Hunting Down HIV-1 Gag Proteins at the Plasma Membrane of Human T Lymphocytes. PMID- 27267416 TI - Descriptive Characteristics and Initial Psychometric Properties of the Non Suicidal Self-Injury Disorder Scale. AB - Non-suicidal self-injury (NSSI) is highly prevalent and associated with tissue damage, emotional distress, and psychiatric disorders. While often discussed in the context of Borderline Personality Disorder and suicide, research demonstrates that NSSI is distinct from these constructs and should be viewed as an independent diagnostic category. Recently, Non-Suicidal Self-Injury Disorder (NSSID) was included in the revised Diagnostic and Statistical Manual of Mental Disorders as a condition for further study. In this article, we describe the properties of a self-report measure designed to assess proposed criteria for NSSID. Undergraduate students at 2 large, public universities completed the NSSID Scale (NSSIDS) along with other measures of NSSI characteristics and psychopathology. Among participants with a history of NSSI, approximately half (54.55%) met diagnostic criteria for NSSID. Participants were most frequently excluded from an NSSID diagnosis on the basis of criterion A (frequency of NSSI) and criterion E (distress or impairment related to NSSI), while participants were least likely to be excluded from diagnosis on the basis of criterion D (NSSI method exclusions) and criterion F (diagnostic "rule-outs"). Consistent with previous literature, the most commonly reported precipitants to NSSI were negative feelings or thoughts (criterion C2). Participants who met criteria for NSSID reported more severe depression, anxiety, and NSSI than participants who engaged in NSSI but did not meet criteria for NSSID. These results support the use of the NSSIDS as a reliable and valid self-report measure of NSSID symptoms. PMID- 27267421 TI - Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure. AB - Catalytic carbonylations of organohalides are important C-C bond formations in chemical synthesis. Carbonylations of unactivated alkyl halides remain a challenge and currently require the use of alkyl iodides under harsh conditions and high pressures of CO. Herein we report a palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure (2 atm CO) under mild conditions. Preliminary mechanistic studies are consistent with a hybrid organometallic-radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide. PMID- 27267422 TI - Unexpected Role of p-Toluenesulfonylmethyl Isocyanide as a Sulfonylating Agent in Reactions with alpha-Bromocarbonyl Compounds. AB - The reactions of p-toluenesulfonylmethyl isocyanide (TosMIC) with alpha bromocarbonyl compounds leading efficiently to alpha-sulfonated ketones, esters, and amides were reported, in which an explicit new role of TosMIC as the sulfonylating agent was uncovered for the first time. Mechanistic study by control experiments and DFT calculations suggested that the reaction is initiated by Cu(OTf)2-catalyzed hydration of TosMIC to form a formamide intermediate, which undergoes facile C-S bond cleavage under the mediation of a Cs2CO3 additive. PMID- 27267423 TI - Concentrations and human health implications of heavy metals in wild aquatic organisms captured from the core area of Daya Bay's Fishery Resource Reserve, South China Sea. AB - Heavy metal concentrations in edible organisms from the core area of Daya Bay's Fishery Resource Reserve, South China Sea, were determined. Samples of 14 crustacean, fish, and shellfish species were collected and analyzed. The As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn concentrations were 0.18-1.16, 0.002-0.919, 0.40-2.85, 0.07-4.10, 0.004-0.055, 0.14-1.19, 0.014-0.070, and 4.57-15.94MUg/g wet weight, respectively. The As concentrations were higher than the Chinese maximum permissible levels in all of the fish and shellfish species and two crustacean species, indicating that consumption of these wild species by humans may pose health risks. However, calculations of the health risks posed to humans indicated that no significant adverse health effects would be associated with consuming these species. PMID- 27267424 TI - A reliable, non-invasive technique for measuring growth in tadpoles exposed to salt. AB - The use of chemical de-icers raises salt levels in roadside streams and ponds, which has adverse effects on tadpole development. Experiments on the effects of de-icers on tadpole development are often hampered by difficulties measuring body size without introducing handling stress that may skew results or cause unintended mortality. We have found a linear relationship between surface area and body mass in tadpoles that is unaffected by exposure to salt. Measuring surface area is therefore a suitable technique whose use should be encouraged when investigating the effects of salt exposure on tadpole growth and development. PMID- 27267425 TI - miRNA-216 and miRNA-499 target cyb561d2 in zebrafish in response to fipronil exposure. AB - MicroRNA (miRNA) can regulate the expression of its target gene by mediating mRNA cleavage or by translational repression at a post-transcriptional level. Usually, one miRNA may regulate many genes as its targets, while one gene may also be targeted by many miRNAs. We previously demonstrated that cyb561d2, whose protein product is involved in cell defense, and chemical stress, is targeted by miR-155 in adult zebrafish (Danio rerio) when exposed to fipronil (5-amino-1-[2,6 dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulphinyl]-1H-pyrazole 3-carbonitrile). Microcosm Targets prediction showed that the cyb561d2 gene is also highly possibly targeted by miR-194a, miR-216b, miR-429, and miR-499. These interactions need to be further validated experimentally. In this study, we evaluated the effects of fipronil on miR-194a, miR-216b, miR-429, miR-499 and cyb561d2 in zebrafish and investigated whether these four miRNAs could regulate the expression of cyb561d2 in both mRNA and protein levels. The expression of cyb561d2 was upregulated in both mRNA and protein level in a dose-dependent manner upon stimulation of fipronil, and miR-216b and miR-499 were downregulated concurrently, whereas there was no significant changes were observed in the expression level of miR-194a and miR-429. The dual luciferase report assay demonstrated that miR-216b and miR-499 interacted with cyb561d2 3'-untranslated regions (3'-UTR), miR-194a and miR-429 did not stimulate degradation of cyb561d2 mRNA. The expression of cyb561d2 was reduced in both mRNA and protein level when ZF4 cells were transfected with miR-499 mimic, whereas expression level of both mRNA and protein was increased when endogenous miR-499 was inhibited by transfection with miR-499 inhibitor. Likewise, the mRNA and protein level of cyb561d2 was affected by treatment with the mimics and the inhibitor of miR-216b. In contrast, when ZF4 cells were transfected with a mimic of miR-194a or miR-429, the expression of cyb561d2 mRNA was not significantly changed. As a result, cyb561d2 is targeted by miR-155, miR-216b and miR-499 upon fipronil exposure, and miR-194a and miR-429 can not target cyb561d2. The expression pattern of these 3 miRNAs presents novel fipronil responses that could be used as a toxicological biomarker. PMID- 27267427 TI - Deprotonation Induced Ligand Oxidation in a Ni(II) Complex of a Redox Noninnocent N(1)-(2-Aminophenyl)benzene-1,2-diamine and Its Use in Catalytic Alcohol Oxidation. AB - Two nickel(II)-complexes, [Ni(II)(H3L)2](ClO4)2 ([1](ClO4)2) and [Ni(II)(HL)2] (2), containing the redox-active tridentate ligand N(1)-(2-aminophenyl)benzene 1,2-diamine (H3L) have been synthesized. Complex [1](ClO4)2 is octahedral containing two neutral H3L ligands in a facial coordination mode, whereas complex 2 is a singlet diradical species with approximately planar configuration at the tetracoordinate metal atom with two pendant NH2 side arms from each of the coordinated ligands. Both complexes are found to be chemically interconvertible; complex [1](2+) gets converted to complex 2 when exposed to base and oxygen via simultaneous deprotonation and oxidation of the coordinated ligands. Molecular and electronic structures of the isolated complexes are scrutinized thoroughly by various spectroscopic techniques, single crystal X-ray crystallography, and density functional theory. The observed dissociation of a ligand arm upon oxidation of the ligand was exploited to bring about catalytic alcohol oxidation using coordinatively saturated complex [1](ClO4)2 as a catalyst precursor. Both the complexes [1](ClO4)2and 2 were tested for catalytic oxidation of both primary and secondary alcohols. PMID- 27267426 TI - Shift from darbepoetin-alpha to continuous erythropoietin receptor activator decreases serum aluminium concentration in patients on hemodialysis. AB - OBJECTIVE: The response of erythropoietic stimulating agents (ESA) in uremic patients may be associated with the changes of biochemical parameters, metal elements and inflammation status during the shift from one ESA to another. METHOD: We compared changes in above mentioned factors after switching from darbepoetin-alpha (DPO) 20MUg weekly for 10 weeks to continuous erythropoietin receptor activator (CERA) 100MUg monthly for 10 weeks in uremic patients on hemodialysis. The haematocrit (Hct), metal elements and inflammation status are the primary outcome. Subjects included 54 patients without transfusion or bleeding or additional ESAs. Responders (IR, n=36) were defined as patients with an increase in Hct after the swtich. RESULT: Although there was no significant difference in overall mean Hct after the switch (p=0.135), there are significantly greater mean number of red blood cells (RBC) (p=0.006), higher platelet numbers (p=0.001), larger RBCs (p=0.017) and higher creatinine (p=0.04) and total cholesterol (T-CHOL) (p=0.003) levels. Mean overall aluminium (Al) level decreased significantly (p=0.001). C-reactive protein (CRP) also decreased (p=0.016). The overall LDH increased (p=0.049) and potassium decreased significantly (p=0.036), which indicating active erythropoiesis. The calcium (Ca) level was significantly higher (p=0.034) and phosphate was significantly lower (p=0.028) after the shift. Although there was no significant increase in overall levels of parathyroid hormone (PTH) after the shift (p=0.061), but the pre-shift and post-shift PTH level was significantly higher in IRs than in non-IRs (p=0.003 and p=0.027, respectively). IRs had a significantly lower initial T-CHOL (p=0.03) and initial CRP (p=0.012) than non-responders, which may be related to lower inflammation. CONCLUSION: We found the shift from DPO to CERA results in lower Al levels, a reduced inflammatory response, and an increase in RBC number and PTH level in uremic patients on hemodialysis. PMID- 27267428 TI - Effects of Bulky Substituents of Push-Pull Porphyrins on Photovoltaic Properties of Dye-Sensitized Solar Cells. AB - To evaluate the effects of substituent bulkiness around a porphyrin core on the photovoltaic properties of porphyrin-sensitized solar cells, long alkoxy groups were introduced at the meso-phenyl group (ZnPBAT-o-C8) and the anchoring group (ZnPBAT-o-C8Cn, n = 4, 8) of an asymmetrically substituted push-pull porphyrin with double electron-donating diarylamino groups and a single electron withdrawing carboxyphenylethynyl anchoring group. The spectroscopic and electrochemical properties of ZnPBAT-o-C8 and ZnPBAT-o-C8Cn were found to be superior to those of a push-pull porphyrin reference (YD2-o-C8), demonstrating their excellent light-harvesting and redox properties for dye-sensitized solar cells. A power conversion efficiency (eta) of the ZnPBAT-o-C8-sensitized solar cell (eta = 9.1%) is higher than that of the YD2-o-C8-sensitized solar cell (eta = 8.6%) using iodine-based electrolyte due to the enhanced light-harvesting ability of ZnPBAT-o-C8. In contrast, the solar cells based on ZnPBAT-o-C8Cn, possessing the additional alkoxy chains in the anchoring group, revealed the lower eta values of 7.3% (n = 4) and 7.0% (n = 8). Although ZnPBAT-o-C8Cn exhibited higher resistance at the TiO2-dye-electrolyte interface by virtue of the extra alkoxy chains, the reduced amount of the porphyrins on TiO2 by excessive addition of coadsorbent chenodeoxycholic acid (CDCA) for mitigating the aggregation on TiO2 resulted in the low eta values. Meanwhile, the ZnPBAT-o-C8 sensitized solar cell showed the lower eta value of 8.1% than the YD2-o-C8 sensitized solar cell (eta = 9.8%) using cobalt-based electrolyte. The smaller eta value of the ZnPBAT-o-C8-sensitized solar cell may be attributed to the insufficient blocking effect of the bulky substituents of ZnPBAT-o-C8 under the cobalt-based electrolyte conditions. Overall, the alkoxy chain length and substitution position around the porphyrin core are important factors to affect the cell performance. PMID- 27267429 TI - Sodium pyrophosphate enhances iron bioavailability from bouillon cubes fortified with ferric pyrophosphate. AB - Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2.5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0.005) when comparing bouillons fortified with FePP only (4.4 %) and bouillons fortified with FePP+NaPP (6.4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33.8 and 27.8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well. PMID- 27267430 TI - Decreasing incidence of type 2 diabetes mellitus in the United States, 2007-2012: Epidemiologic findings from a large US claims database. AB - AIMS: To explore epidemiological trends in type 2 diabetes mellitus (T2D) in the US between 2007 and 2012 using a large US claims database, with a particular focus on demographics, prevalence, newly-diagnosed cases, and comorbidities. METHODS: Truven Health MarketScan(r) Databases were used to identify patients with claims evidence of T2D in the years 2007 and 2012. Newly-diagnosed T2D was characterized by an absence of any T2D claims or related drug claims for 6months preceding the index claim. Demographic and comorbidity characteristics of the prevalent and new-onset T2D groups were compared and analyzed descriptively for trends over time. RESULTS: The overall prevalence of T2D remained stable from 2007 (1.24 million cases/15.07 million enrolled; 8.2%) to 2012 (2.04 million cases/24.52 million enrolled; 8.3%), while the percentage of newly-diagnosed cases fell dramatically from 2007 (152,252 cases; 1.1%) to 2012 (147,011 cases; 0.65%). The mean age of patients with prevalent T2D was similar in 2007 (60.6y) and 2012 (60.0y), while the mean age of newly-diagnosed T2D patients decreased by 3years from 2007 (57.7y) to 2012 (54.8y). Hypertension and hyperlipidemia were the most common comorbidities, evident in 50-75% of T2D patients, and increased markedly from 2007 to 2012 in both prevalent and new-onset T2D populations. Cardiovascular disease decreased slightly in prevalent (-0.9%) and new-onset ( 2.8%) cases. CONCLUSIONS: This large US health claims database analysis suggests stabilization in prevalence and declining incidence of T2D over a recent 5-year period, a downward shift in age at T2D diagnosis, but increases in several comorbidities. PMID- 27267431 TI - Lispro administered by the QS-M Needle-Free Jet Injector generates an earlier insulin exposure. AB - OBJECTIVE: The aim of this study is to evaluate the pharmacokinetic and pharmacodynamic (PK-PD) profiles of lispro administered by the QS-M needle-free jet injector in Chinese subjects. RESEARCH DESIGN AND METHODS: A randomized, double-blind, double-dummy, cross-over study was performed. Eighteen healthy volunteers were recruited. Lispro (0.2 units/kg) was administered by the QS-M needle-free jet injector or by conventional pen. Seven-hour euglycemic clamp tests were performed. RESULTS: A larger area under the curve (AUCs) of insulin concentration and glucose infusion rate (GIR) during the first 20 minutes after lispro injection by the jet injector compared to the insulin pen was observed (24.91 +/- 15.25 vs. 12.52 +/- 7.60 mg. kg(-1), P < 0.001 for AUCGIR,0-20 min; 0.36 +/- 0.24 vs. 0.10 +/- 0.04 U min L(-1), P < 0.001 for AUCINS, 0-20 min). Needle-free injection showed a shorter time to reach maximum insulin concentration (37.78 +/- 11.14 vs. 80.56 +/- 37.18 min, P < 0.001) and GIR (73.24 +/- 29.89 vs. 116.18 +/- 51.89 min, P = 0.006). There were no differences in total insulin exposure and hypoglycemic effects between the two devices. CONCLUSION: Lispro administered by QS-M needle-free injector results in earlier and higher insulin exposure than conventional pen, and a greater early glucose lowering effect with similar overall potency. PMID- 27267432 TI - Polymer-Embedded Fabrication of Co2P Nanoparticles Encapsulated in N,P-Doped Graphene for Hydrogen Generation. AB - We developed a method to engineer well-distributed dicobalt phosphide (Co2P) nanoparticles encapsulated in N,P-doped graphene (Co2P@NPG) as electrocatalysts for hydrogen evolution reaction (HER). We fabricated such nanostructure by the absorption of initiator and functional monomers, including acrylamide and phytic acid on graphene oxides, followed by UV-initiated polymerization, then by adsorption of cobalt ions and finally calcination to form N,P-doped graphene structures. Our experimental results show significantly enhanced performance for such engineered nanostructures due to the synergistic effect from nanoparticles encapsulation and nitrogen and phosphorus doping on graphene structures. The obtained Co2P@NPG modified cathode exhibits small overpotentials of only -45 mV at 1 mA cm(-2), respectively, with a low Tafel slope of 58 mV dec(-1) and high exchange current density of 0.21 mA cm(-2) in 0.5 M H2SO4. In addition, encapsulation by N,P-doped graphene effectively prevent nanoparticle from corrosion, exhibiting nearly unfading catalytic performance after 30 h testing. This versatile method also opens a door for unprecedented design and fabrication of novel low-cost metal phosphide electrocatalysts encapsulated by graphene. PMID- 27267433 TI - Steady-State and Time-Resolved Studies into the Origin of the Intrinsic Fluorescence of G-Quadruplexes. AB - Stretches of guanines in DNA and RNA can fold into guanine quadruplex structures (GQSs). These structures protect telomeres in DNA and regulate gene expression in RNA. GQSs have an intrinsic fluorescence that is sensitive to different parameters, including loop sequence and length. However, the dependence of GQS fluorescence on solution and sequence parameters and the origin of this fluorescence are poorly understood. Herein we examine effects of dangling nucleotides and cosolute conditions on GQS fluorescence using both steady-state and time-resolved fluorescence spectroscopy. The quantum yield of dGGGTGGGTGGGTGGG, termed "dG3T", is found to be modest at ~2 * 10(-3). Nevertheless, dG3T and its variants are significantly brighter than the common nucleic acid fluorophore 2-aminopurine (2AP) largely due to their sizable extinction coefficients. Dangling 5'-end nucleotides generally reduce emission and blue-shift the resultant spectrum, whereas dangling 3'-end nucleotides slightly enhance fluorescence, particularly on the red side of the emission band. Time-resolved fluorescence decays are broadly distributed in time and require three exponential components for accurate fits. Time-resolved emission spectra suggest the presence of two emitting populations centered at ~330 and ~390 nm, with the redder component being a well-defined long-lived (~1 ns) entity. Insights into GQS fluorescence obtained here should be useful in designing brighter intrinsic RNA and DNA quadruplexes for use in label-free biotechnological applications. PMID- 27267434 TI - Pharmacophore modeling, comprehensive 3D-QSAR, and binding mode analysis of TGR5 agonists. AB - Takeda G-protein-coupled receptor 5 (TGR5) is emerging as an important and promising target for the development of anti-diabetic drugs. Pharmacophore modeling and atom-based 3D-QSAR studies were carried out on a new series of 5 phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. The generated best six featured pharmacophore model AAHHRR consists of two hydrogen bond acceptors (A): two hydrophobic groups (H) and two aromatic rings (R). The constructed 3D-QSAR model acquired excellent correlation coefficient value (R2 = 0.9018), exhibited good predictive power (Q2 = 0.8494) and high Fisher ratio (F = 61.2). The pharmacophore model was validated through Guner Henry (GH) scoring method. The GH value of 0.5743 indicated that the AAHHRR model was statistically valuable and reliable in the identification of TGR5 agonists. Furthermore, the combined approach of molecular docking and binding free energy calculations were carried out for the 5-phenoxy-1,3-dimethyl-1H-pyrazole-4 carboxamides to explore the binding mode and interaction pattern. The generated contour maps revealed the important structural insights for the activity of the compounds. The results obtained from this study could be helpful in the development of novel and more potent agonists of TGR5. PMID- 27267435 TI - Erratum. PMID- 27267436 TI - Modified Karydakis procedure for giant pilonidal sinus. PMID- 27267437 TI - Nanostructural Characterization of Kidney Stones as a Tool for Hardness Evaluation and Nanomedicine Development. PMID- 27267438 TI - Development of Obesity: Mechanisms and Physiology. AB - Normal adult animals living in nonstressful environments that receive nutritionally sound diets balance their energy expenditure with their energy intake over the long-term. Most knowledge of mechanisms underlying the precise balance of energy is derived from research on rodent models and human correlates. This knowledge is believed applicable and pertinent for understanding causes of obesity in dogs and cats. The roles of satiation and adiposity feedback, cognitive input, energy expenditure, and physical activity are reviewed. Dietary and environmental factors especially relevant to promotion of overweight body condition are reviewed. These include dietary fat and palatability, inactive and stressful lifestyle, and obesogenic effects of neutering. PMID- 27267439 TI - Other Risks/Possible Benefits of Obesity. AB - Obesity is not a cosmetic or social issue; it is an animal health issue. The metabolic effects of obesity on insulin resistance and development of hyperlipidemia and the mechanical stress excess weight places on the musculoskeletal system are well established in the literature. Additional health risks from obesity, such as fatty accumulation in the liver, intestinal bacterial dysbiosis, and changes to renal architecture, are less well understood, but have been demonstrated to occur clinically in obese animals and may lead to deleterious long-term health effects. Keeping dogs and cats lean lowers their risk for development of certain diseases and leads to a longer and better quality of life. PMID- 27267440 TI - Can symptoms help in differential diagnosis between substance-induced vs independent psychosis in adults with a lifetime diagnosis of cocaine use disorder? AB - The main goal of this study it is explore the psychopathological differences between IPD and SIPD in a sample of 125 adults with a lifetime diagnosis of cocaine disorder recruited from treatment setting and through street contacts. A secondary analysis of six cross-sectional studies was conducted between 2000 and 2010. SIPD and IPD were diagnosed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). 38 subjects (30.4%) were diagnosed with lifetime IPD and 87 (69.6%) with lifetime SIPD. A binomial logistic regression analysis using SIPD as the reference group showed that only previous prison admissions (OR 2.59; 95% CI 1.05, 6.36) and visual hallucinations (OR 5.21; 95% CI 1.54, 17.65) remained significant variables in the group with lifetime SIPD. In the group with lifetime IPD, grandiose delusions (OR 0.19; 95% CI 0.06, 0.60) and disorganized speech (OR 0.16; 95% CI 0.04, 0.61) remained significant. Model predicts the diagnosis of lifetime SIPD with a sensitivity of 80.3% and a specificity of 78.2%. This clinical profile of lifetime SIPD could help distinguish between IPD and SIPD among adults with lifetime diagnosis of cocaine disorder. PMID- 27267441 TI - CRY1 and CRY2 genetic variants in seasonality: A longitudinal and cross-sectional study. AB - Cryptochromes are key components of the circadian clocks that generate and maintain seasonal variations. The aim of our study was to analyze the associations of CRY1 and CRY2 genetic variants with the problematicity of seasonal variations, and whether the problematicity of seasonal variations changed during the follow-up of 11 years. Altogether 21 CRY1 and 16 CRY2 single nucleotide polymorphisms (SNPs) were genotyped and analyzed in 5910 individuals from a Finnish nationwide population-based sample who had filled in the self report on the seasonal variations in mood and behavior in the year 2000. In the year 2011, 3356 of these individuals filled in the same self-report on the seasonal variations in mood and behavior. Regression models were used to test whether any of the SNPs associated with the problematicity of seasonal variations or with a change in the problematicity from 2000 to 2011. In the longitudinal analysis, CRY2 SNP rs61884508 was protective from worsening of problematicity of seasonal variations. In the cross-sectional analysis, CRY2 SNP rs72902437 showed evidence of association with problematicity of seasonal variations, as did SNP rs1554338 (in the MAPK8IP1 and downstream of CRY2). PMID- 27267443 TI - Foreword. PMID- 27267442 TI - Flourishing after depression: Factors associated with achieving complete mental health among those with a history of depression. AB - This study investigated factors associated with complete mental health among a nationally representative sample of Canadians with a history of depression by conducting secondary analysis of the 2012 Canadian Community Health Survey- Mental Health (n=20,955). Complete mental health was defined as 1) the absence of mental illness, substance abuse, or suicidal ideation in the past year; 2) happiness or life satisfaction almost every day/past month, and 3) social and psychological well-being. The prevalence of complete mental health among those with and without a history of depression was determined. In a sample of formerly depressed respondents (n=2528), a series of logistic regressions were completed controlling for demographics, socioeconomic status, health and lifetime mental health conditions, health behaviours, social support, adverse childhood experiences, and religiosity. Two in five individuals (39%) with a history of depression had achieved complete mental health in comparison to 78% of those without a history of depression. In comparison to the formally depressed adults who were not in complete mental health, those in complete mental health were more likely to be female, White, older, affluent, married, with a confidant, free of disabling pain, insomnia, and childhood adversities and without a history of substance abuse. They were also more likely to exercise regularly and use spirituality to cope. PMID- 27267445 TI - Pharmacologic and non-pharmacologic treatments for chronic pain in individuals with HIV: a systematic review. AB - Chronic pain occurs in as many as 85% of individuals with HIV and is associated with substantial functional impairment. Little guidance is available for HIV providers seeking to address their patients' chronic pain. We conducted a systematic review to identify clinical trials and observational studies that examined the impact of pharmacologic or non-pharmacologic interventions on pain and/or functional outcomes among HIV-infected individuals with chronic pain in high-development countries. Eleven studies met inclusion criteria and were mostly low or very low quality. Seven examined pharmacologic interventions (gabapentin, pregabalin, capsaicin, analgesics including opioids) and four examined non pharmacologic interventions (cognitive behavioral therapy, self-hypnosis, smoked cannabis). The only controlled studies with positive results were of capsaicin and cannabis, and had short-term follow-up (<=12 weeks). Among the seven studies of pharmacologic interventions, five had substantial pharmaceutical industry sponsorship. These findings highlight several important gaps in the HIV/chronic pain literature that require further research. PMID- 27267444 TI - MYC interaction with the tumor suppressive SWI/SNF complex member INI1 regulates transcription and cellular transformation. AB - MYC is a key driver of cellular transformation and is deregulated in most human cancers. Studies of MYC and its interactors have provided mechanistic insight into its role as a regulator of gene transcription. MYC has been previously linked to chromatin regulation through its interaction with INI1 (SMARCB1/hSNF5/BAF47), a core member of the SWI/SNF chromatin remodeling complex. INI1 is a potent tumor suppressor that is inactivated in several types of cancers, most prominently as the hallmark alteration in pediatric malignant rhabdoid tumors. However, the molecular and functional interaction of MYC and INI1 remains unclear. Here, we characterize the MYC-INI1 interaction in mammalian cells, mapping their minimal binding domains to functionally significant regions of MYC (leucine zipper) and INI1 (repeat motifs), and demonstrating that the interaction does not interfere with MYC-MAX interaction. Protein-protein interaction network analysis expands the MYC-INI1 interaction to the SWI/SNF complex and a larger network of chromatin regulatory complexes. Genome-wide analysis reveals that the DNA-binding regions and target genes of INI1 significantly overlap with those of MYC. In an INI1-deficient rhabdoid tumor system, we observe that with re-expression of INI1, MYC and INI1 bind to common target genes and have opposing effects on gene expression. Functionally, INI1 re expression suppresses cell proliferation and MYC-potentiated transformation. Our findings thus establish the antagonistic roles of the INI1 and MYC transcriptional regulators in mediating cellular and oncogenic functions. PMID- 27267446 TI - Availability of evidence on cataract in low/middle-income settings: a review of reviews using evidence gap maps approach. AB - BACKGROUND: Despite high-quality evidence being essential for planning and delivering eye health programmes, evidence on what works is relatively scarce. To address this need, we developed eye health Evidence Gap Maps (EGMs) with the first one focusing on cataract. These maps summarise, critically appraise and present evidence in a user-friendly format. This paper presents experiences of developing the cataract gap map and discusses the challenges and benefits of the process. METHODS: Following a comprehensive search of relevant databases, we sifted and extracted data from all relevant reviews on cataract. Critical appraisal was conducted by two reviewers independently using Supported the Use of Research Evidence checklist and a summary quality assessment was shared with the authors for comments. RESULTS: A total of 52 reviews were included in the map. The majority of the reviews addressed quality of clinical care (20) and types of treatment (18). Overall, 30 reviews provided strong evidence in response to the research question, 14 reviews showed weak or no evidence and in 14 reviews the results were inconclusive. 14 reviews were regarded as high quality, 12 were medium quality and 26 were graded as low quality. To verify the validity of the Supporting the Use for Research Evidence (SURE) checklist, studies were also appraised using the Scottish Intercollegiate Guidelines Network (SIGN) tool. Based on the kappa statistics test, results showed excellent agreement between the two checklists (K=0.79). DISCUSSION: EGMs support policy makers and programme managers to make informed decisions and enable researchers to prioritise future work based on the most evident gaps on knowledge. PMID- 27267447 TI - Treatment of severe chronic ocular graft-versus-host disease using 100% autologous serum eye drops from a sealed manufacturing system: a retrospective cohort study. AB - BACKGROUND/AIMS: To analyse patients with chronic ocular graft-versus-host disease (GvHD) under treatment with 100% autologous serum eye drops from a sealed manufacturing system. METHODS: 17 patients with chronic ocular GvHD received 100% autologous serum eye drops from single use vials manufactured in a sealed system. Retrospective analysis included visual acuity, corneal staining, frequency of artificial tears, ocular symptoms by means of a questionnaire and information on subjective side effects and cost compensation. RESULTS: Data of prior to autologous serum eye drops therapy and at a 6-month follow-up were obtained. They demonstrated a significant increase in visual acuity (logMAR oculus dexter/right eye (OD) 0.5+/-0.32 to 0.4+/-0.3; oculus sinister/left eye (OS) 0.6+/-0.35 to 0.3+/-0.35; p=0.177/0.003) and significant improvement in corneal staining (Oxford grading scheme: OD from 3+/-1.03 to 2+/-1.43, OS from 4+/-1.0 to 2+/ 1.09, p=0.004/0.001) and ocular symptoms (ocular surface disease index: 88+/ 20.59 to 63+/-22.77; p=0.02). Frequency of artificial tears was reduced and no side effects were reported. Patient satisfaction was 100%, and cost compensation by health insurance reached 80%. CONCLUSIONS: 100% autologous serum eye drops using a sealed manufacturing system were efficient in improving the ocular surface, patient symptoms and visual acuity without side effects. It seems to be safe to use 100% autologous serum despite earlier suspicions regarding immune complex accumulations and exacerbation of ocular surface inflammation. The potential effects of serum levels of systemic immunosuppressives through readministration onto the ocular surface need to be elucidated. PMID- 27267448 TI - Incidence of optic canal fracture in the traumatic optic neuropathy and its effect on the visual outcome. AB - OBJECTIVE: To correlate the intraoperative endoscopic findings with high resolution CT (HRCT) for the diagnosis of optic canal fractures (OCF). To compare the visual outcome of patients with different types of OCF and without. DESIGN: A retrospective, comparative case series. PARTICIPANTS: 1275 consecutive patients (1275 eyes) with indirect traumatic optic neuropathy (TON). METHODS: Altogether, 1275 patients who underwent endoscopic transethmoid optic canal decompression (ETOCD) for unilateral indirect TON were reviewed from 1 October 2006 to 30 September 2014. HRCT performed prior to surgery were compared with findings during surgery. The visual outcomes before and after surgery were also compared. MAIN OUTCOME MEASURES: The presence and type of OCF detected by HRCT and during surgery; visual acuity prior to surgery and at 3 months after surgery. RESULTS: A total of 1275 patients (1275 eyes) were included, with 708 patients that had OCF visible on HRCT image. During surgery, an additional 187 (20.9%) patients with OCF were noticed. Among these, 136 had undisplaced fractures, most of which were linear intracanalicular fractures. The initial visual acuity of patients with OCF was worse than that of patients without OCF (p<0.01). However, no statistical difference existed in the final visual acuity at 3 months after surgery (>0.05). Significant statistical difference of surgical efficacy existed between all the patients with OCF and without OCF (p<0.001). CONCLUSIONS: Among patients with OCF, 20.9% were not detected by HRCT. Patients with OCF had a worse initial visual acuity than those without OCF. There was no significant difference in final visual acuity after ETOCD. PMID- 27267449 TI - Indocyanine-green-guided targeted laser photocoagulation of capillary macroaneurysms in macular oedema: a pilot study. AB - AIMS: In longstanding diabetic macular oedema (DME) or retinal vein occlusion (RVO), capillary macroaneurysms may develop. Indocyanine green angiography (ICGA) has been shown to optimise their detection. Here, we report the anatomical and functional outcome of the elective photocoagulation of capillary macroaneurysms. METHODS: A retrospective, interventional, two-centre study. In eyes with chronic macular oedema and severe hard exsudates due to diabetic retinopathy or RVO, the presence of capillary macroaneurysms (defined by a diameter larger than 150 um) was assessed by ICGA and optical coherence tomography (OCT). Capillary macroaneurysms were selectively photocoagulated, the presence of photothrombosis within the lumen being assessed by immediate OCT. RESULTS: Four eyes from three patients with DME and five eyes from five patients with RVO were included. The median duration of visual loss was 4 years. Median initial visual acuity (VA) was 20/200. The median number of capillary macroaneurysms per eye was 2 (range, 1-8) and their median size was 410 um (range, 154-603). Six months after photocoagulation, there was a significant reduction in macular thickness (mean+/ SD, 528 um+/-200 vs 271 um+/-152, p<0.05) and improvement of VA (mean log MAR, 0.82 vs 0.58, p<0.05). CONCLUSIONS: During macular oedema with severe hard exsudates due to DME or RVO, systematic detection of capillary macroaneurysms by ICGA followed by their OCT-controlled photocoagulation may be of interest. These results may contribute to re-evaluate the role of photocoagulation in the management of longstanding macular oedema. PMID- 27267450 TI - Longitudinal comparison of femtosecond-assisted sub-Bowman keratomileusis versus photorefractive keratectomy for high myopia. AB - PURPOSE: To longitudinally compare the visual and refractive outcomes and changes in corneal thickness between femtosecond-assisted sub-Bowmen keratomileusis (SBK) and photorefractive keratectomy (PRK) with mitomycin C in eyes with high myopia. METHODS: Patients with spherical equivalent >=6 dioptres (D) who underwent femtosecond-assisted SBK or PRK with mitomycin C were recruited. All patients were examined preoperatively and after 1 week, and, 1, 3, 6 and 12 months postoperatively. Assessments included uncorrected and best-corrected distance visual acuity , and manifest refraction spherical equivalent. Corneal thickness was measured using swept source optical coherence tomography. RESULTS: A total of 110 eyes were included (68 PRK, 42 SBK). Change in efficacy index and safety index was not significantly different between both groups beyond 1 week postoperatively (p>=0.116). Manifest refraction spherical equivalent changed significantly from -9.02+/-1.92 D preoperatively to -0.21+/-0.31 D and from 8.25+/-1.10 D preoperatively to -0.53+/-0.55 D at 1 year after PRK and SBK, respectively (p<0.0001). The variance of postoperative refraction was significantly smaller after PRK throughout the 1-year follow-up compared with SBK (p<=0.0024). The central corneal thickness stabilised at 1 week after PRK and 3 months after SBK. CONCLUSIONS: Our study showed that femtosecond-assisted SBK and PRK with mitomycin C have comparable safety and efficacy for correction of high myopia. However, better predictability of postoperative refraction was noted after PRK compared with SBK. PMID- 27267451 TI - New appraisals of Kyrieleis plaques: a multimodal imaging study. AB - PURPOSE: Kyrieleis retinal periarteritis reflects the severe intraocular inflammation experienced by the eye. Its aetiology has not been well established, since only nine cases have been reported and there is no pathological study available in the literature. We determine the pathogenesis of Kyrieleis periarteritis based on interpretation of multimodal imaging findings. METHODS: Charts of patients with Kyrieleis arteritis seen between 2006 and 2014 were retrieved from eight uveitis referral centres throughout the world. Follow-up ranged from 5 to 12 months. RESULTS: Twenty-five eyes with Kyrieleis arteritis from 25 patients were included in the study. Nineteen patients (72%) were male and six (28%) were female. Twenty-three patients were diagnosed with toxoplasmosis retinochoroiditis and two patients had cytomegalovirus retinitis. Fluorescein angiography, fundus autofluorescence and indocyanine green angiography were performed on 25/25 (100%) eyes. In eight eyes (32%), baseline spectral domain optical coherence tomography (SD-OCT) scans were performed along the segmental Kyrieleis arteritis. Fluorescein angiography showed early hypofluorescence and intermediate hyperfluorescence associated with the areas of focal arteritis, whereas indocyanine green angiography of these accumulations showed early hypofluorescence and late hyperfluorescence. Fundus autofluorescence revealed an increased autofluorescence of the vessels corresponding to the Kyrieleis plaques, while SD-OCT scans along the segmental Kyrieleis arteritis showed hyperreflectivity of the vessel wall. CONCLUSIONS: These imaging modalities provide in vivo, quasi-histologic images demonstrating that Kyrieleis plaques are characterised by an inflammatory involvement within the vessels' endothelium. PMID- 27267452 TI - Improving Synthetic Biology Communication: Recommended Practices for Visual Depiction and Digital Submission of Genetic Designs. AB - Research is communicated more effectively and reproducibly when articles depict genetic designs consistently and fully disclose the complete sequences of all reported constructs. ACS Synthetic Biology is now providing authors with updated guidance and piloting a new tool and publication workflow that facilitate compliance with these recommended practices and standards for visual representation and data exchange. PMID- 27267453 TI - Corynebacteriumpollutisoli sp. nov., isolated from hexachlorocyclohexane contaminated soil. AB - A Gram-stain-positive, alkaliphilic, non-spore-forming, non-motile bacterium, designated VDS11T, was isolated from a soil sample collected from the hexachlorocyclohexane dumpsite, located at Ummari Village, Lucknow, Uttar Pradesh, India. 16S rRNA gene sequence analysis indicated that strain VDS11T occupies a distinct phylogenetic position within the genus Corynebacterium, showing the highest sequence similarity with Corynebacterium humireducens MFC-5T (98.7 %) and Corynebacterium nasicanis 2673/12T (98.4 %). The DNA G+C content was 50.6 mol% and the DNA-DNA hybridization (DDH) relatedness value with C. humireducens MFC-5T and C. nasicanis 2673/12T was 49.7 and 39.6 %, respectively. Strain VDS11T contained C16 : 0 (28.3), C18 : 1omega9c (52.3), C18 : 0 (1.3) and C20 : 0 (3.0) as the major cellular fatty acids. The major isoprenoid quinone was MK-9(H2). Strain VDS11T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, unidentified aminolipids, glycolipids, phospholipids and unidentified lipids as the major polar lipids. The peptidoglycan type was A31 (meso 2, 6-diaminopimelic acid, directly cross-linked). Based on the results of DDH studies and the biochemical and physiological data, strain VDS11T represents a novel species of the genus Corynebacteriumfor which the name Corynebacterium pollutisoli sp. nov., has been proposed. The type strain is VDS11T(=DSM 100104T=MCC 2722T=KCTC 39687T). PMID- 27267454 TI - Pulmonary hypoplasia and anasarca syndrome in Cika cattle. AB - BACKGROUND: Hydrops foetalis is defined as excessive fluid accumulation within the foetal extravascular compartments and body cavities. It has been described in human and veterinary medicine, but despite several descriptive studies its aetiology is still not fully clarified. Pulmonary hypoplasia and anasarca (PHA) syndrome is a rare congenital abnormality in cattle that is characterised by hydrops foetalis including extreme subcutaneous oedema (anasarca) and undeveloped or poorly formed lungs (pulmonary hypoplasia). Until now, sporadic cases of PHA were reported in cattle breeds like Australian Dexter, Belted Galloway, Maine Anjou, and Shorthorn. This report describes the first known cases of PHA syndrome in Slovenian Cika cattle. CASE PRESENTATION: A 13-year-old cow aborted a male calf in the seventh month of pregnancy, while a male calf was delivered by caesarean section on the due date from a 14-year-old cow. The pedigree analysis showed that the calves were sired by the same bull, the dams were paternal half sisters and the second calf was the product of a dam-son mating. Gross lesions were similar in both cases and characterized by severe anasarca, hydrothorax, hydropericardium, ascites, hypoplastic lungs, absence of lymph nodes, and an enlarged heart. The first calf was also athymic. Histopathology of the second affected calf confirmed severe oedema of the subcutis and interstitium of the organs, and pulmonary hypoplasia. The lymph vessels in the subcutis and other organs were severely dilated. Histopathology of the second calf revealed also lack of bronchus associated lymphoid tissue and adrenal gland hypoplasia. CONCLUSIONS: The findings were consistent with known forms of the bovine PHA syndrome. This is the first report of the PHA syndrome occurring in the local endangered breed of Cika cattle. Observed inbreeding practice supports that this lethal defect most likely follows an autosomal recessive mode of inheritance. In the light of the disease phenotype it is assumed that a mutation causing an impaired development of lymph vessels is responsible for the hydrops foetalis associated malformations in bovine PHA. PMID- 27267455 TI - Characterization and classification of adherent cells in monolayer culture using automated tracking and evolutionary algorithms. AB - This paper presents a novel method for tracking and characterizing adherent cells in monolayer culture. A system of cell tracking employing computer vision techniques was applied to time-lapse videos of replicate normal human uro epithelial cell cultures exposed to different concentrations of adenosine triphosphate (ATP) and a selective purinergic P2X antagonist (PPADS), acquired over a 24h period. Subsequent analysis following feature extraction demonstrated the ability of the technique to successfully separate the modulated classes of cell using evolutionary algorithms. Specifically, a Cartesian Genetic Program (CGP) network was evolved that identified average migration speed, in-contact angular velocity, cohesivity and average cell clump size as the principal features contributing to the separation. Our approach not only provides non biased and parsimonious insight into modulated class behaviours, but can be extracted as mathematical formulae for the parameterization of computational models. PMID- 27267456 TI - A cross-sectional study to compare levels of psychiatric morbidity between young people and adults exposed to violence in a large urban center. AB - BACKGROUND: Teenagers and young adults are more exposed to violence and traumatic events than adults, and these factors can be associated with mental disorders. This paper aims at investigating whether young people are more exposed to violence and traumatic events and to compare pattern of mental disorders with adults. METHODS: Cross-sectional study using the Composite International Diagnostic Interview, conducted between 2007 and 2008 with a randomly selected sample of 15 to 75 year-old residents of Sao Paulo, Brazil. RESULTS: Two thousand five hundred thirty-six participants were divided into two groups: 1096 (43.2 %) young people (15 to 24 years), and 1440 (56.8 %) adults (25 to 75 years). 12 month exposure to traumatic events was higher among young people (32.1 % vs. 20.6 %; p < 0.001). Assaultive violence was reported by 13.4 % of young people and 8.6 % of adults (p = 0.012); 20.1 % of young people and 13 % of adults reported suffering other injury or shocking events (p < 0.001); sudden death/life threatening illness of a close person was declared by 6.1 % of young people and 3.2 % of adults (p = 0.017). Prevalence of alcohol related disorders was higher among young people (5.4 % vs. 2.5 %; P = 0.032); depressive disorders were more prevalent among adults (9.0 % vs. 4.7 %; P = 0.004). Alcohol related disorders were associated to assaultive violence among young people (OR = 3.4; 95 % CI = 1.36 to 8.52; p = 0.004) and adults (OR = 2.38; 95 % CI = 1.23 to 4.61; p = 0.002). Phobic/anxiety disorders were associated to other injury or shocking events among young people (OR = 1.28; 95 % CI = 0.67 to 2.44; p = 0.025). Major depressive disorder was associated to assaultive violence among young people (OR = 2.27; 95 % CI = 1.09 to 4.74; p = 0.004) and adults (OR = 1.28; 95 % CI = 0.85 to 1.93; p = 0.009). CONCLUSION: Exposure to violence and traumatic events was higher among young people. Alcohol related disorders, depression and phobic/anxiety disorders were significantly higher among young people exposed to traumatic events. Despite the study design, high exposure to violence and traumatic events in this age group can be considered important factors in triggering mental disorders in this vulnerable age period. PMID- 27267457 TI - Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship-Quasi Experimental Designs. AB - Quasi-experimental studies evaluate the association between an intervention and an outcome using experiments in which the intervention is not randomly assigned. Quasi-experimental studies are often used to evaluate rapid responses to outbreaks or other patient safety problems requiring prompt, nonrandomized interventions. Quasi-experimental studies can be categorized into 3 major types: interrupted time-series designs, designs with control groups, and designs without control groups. This methods paper highlights key considerations for quasi experimental studies in healthcare epidemiology and antimicrobial stewardship, including study design and analytic approaches to avoid selection bias and other common pitfalls of quasi-experimental studies. Infect Control Hosp Epidemiol 2016;1-6. PMID- 27267458 TI - LaCyTools: A Targeted Liquid Chromatography-Mass Spectrometry Data Processing Package for Relative Quantitation of Glycopeptides. AB - Bottom-up glycoproteomics by liquid chromatography-mass spectrometry (LC-MS) is an established approach for assessing glycosylation in a protein- and site specific manner. Consequently, tools are needed to automatically align, calibrate, and integrate LC-MS glycoproteomics data. We developed a modular software package designed to tackle the individual aspects of an LC-MS experiment, called LaCyTools. Targeted alignment is performed using user defined m/z and retention time (tr) combinations. Subsequently, sum spectra are created for each user defined analyte group. Quantitation is performed on the sum spectra, where each user defined analyte can have its own tr, minimum, and maximum charge states. Consequently, LaCyTools deals with multiple charge states, which gives an output per charge state if desired, and offers various analyte and spectra quality criteria. We compared throughput and performance of LaCyTools to combinations of available tools that deal with individual processing steps. LaCyTools yielded relative quantitation of equal precision (relative standard deviation <0.5%) and higher trueness due to the use of MS peak area instead of MS peak intensity. In conclusion, LaCyTools is an accurate automated data processing tool for high-throughput analysis of LC-MS glycoproteomics data. Released under the Apache 2.0 license, it is freely available on GitHub ( https://github.com/Tarskin/LaCyTools ). PMID- 27267459 TI - Outcomes of patients with Goodpasture syndrome: A nationwide cohort-based study from the French Society of Hemapheresis. AB - The overall and renal outcomes of patients with Goodpasture syndrome (GS), a rare autoimmune disorder characterized by circulating anti-GBM antibodies and rapidly progressive glomerulonephritis and/or pulmonary hemorrhage, have mostly been reported in small-sized cohorts or by aggregating patients receiving a variety of therapies that include aggressive (i.e., combined plasma exchanges, corticosteroids, and cyclophosphamide) and less aggressive (i.e., either plasma exchanges or immunosuppressive drugs, or no treatment). To address the prognosis of GS patients with relatively homogeneous management including plasma exchanges, we conducted a multicenter retrospective study on GS patients included in the registry of the French Society of Hemapheresis. 122 patients were included (kidney alone (n = 28), lung alone (n = 5), or combined involvement (n = 89)). All 122 patients received plasma exchanges (median number of sessions: 13 [9 17]), either alone (n = 8) or associated with combined corticosteroids and oral or IV cyclophosphamide (n = 101) or with corticosteroids alone (n = 12) or cyclophosphamide alone (n = 2). One-year survival was 86.9%. 7/16 patients died from severe infection. In multivariate analyses (Cox's regression model), being aged <60 years, and number of plasma exchanges were correlated to overall survival. The use of alternative immunosuppressive drugs (because of refractory or relapsing GS) was correlated to mortality at one year. Superiority of oral cyclophosphamide compared to intravenous intake was close to significant. Using a logistic regression model, renal survival in patients alive at 1 year was only predicted by serum creatinine <500 MUmol/L at presentation. This large series describes the predictive factors for overall and renal survival of GS patients treated by plasma exchanges. Interventional studies that compare oral and intravenous cyclophosphamide, as well as testing new immunosuppressive therapies, are warranted. PMID- 27267460 TI - Infections as risk factor for autoimmune diseases - A nationwide study. AB - Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between hospital admission for an infection and 29 autoimmune diseases. This study shows that infections are risk factors for a broad spectrum of autoimmune diseases in a dose-response and temporal manner, in agreement with the hypothesis that infections are an environmental risk factor contributing to the etiology of autoimmune diseases together with genetic factors. PMID- 27267461 TI - Rb selectively inhibits innate IFN-beta production by enhancing deacetylation of IFN-beta promoter through HDAC1 and HDAC8. AB - Type I IFN production is tightly controlled by host to generate efficient viral clearance without harmful immunopathology or induction of autoimmune disorders. Epigenetic regulation of type I IFN production in innate immunity and inflammatory disorders remains to be fully understood. Several tumor suppressors have been shown to regulate immune response and inflammation. However, the non classical functions of tumor suppressors in innate immunity and inflammatory diseases need further identification. Here we report retinoblastoma protein (Rb) deficiency selectively enhanced TLR- and virus-triggered production of IFN-beta which thus induced more IFN-alpha generation in the later phase of innate stimuli, but had no effect on the production of TNF, IL-6 and early phase IFN alpha in macrophages. Rb1(fl/fl)Lyz2cre(+) Rb-deficient mice exhibited more resistant to lethal virus infection and more effective clearance of influenza virus. Rb selectively bound Ifnb1 enhancer region, but not the promoter of Ifna4, Tnf and Il6, by interacting with c-Jun, the component of IFN-beta enhanceosome. Then Rb recruited HDAC1 and HDAC8 to attenuate acetylation of Histone H3/H4 in Ifnb1 promoter, resulting in suppression of Ifnb1 transcription. Therefore, Rb selectively inhibits innate IFN-beta production by enhancing deacetylation of Ifnb1 promoter, exhibiting a previous unknown non-classical role in innate immunity, which also suggests a role of Rb in the regulation of type I IFN production in inflammatory or autoimmune diseases. PMID- 27267462 TI - Use of long-lasting insecticide-treated bed nets in a population with universal coverage following a mass distribution campaign in Uganda. AB - BACKGROUND: Uganda conducted an LLIN mass distribution campaign in 2013 with the goal of achieving universal coverage. Using data from the 2014 malaria indicator survey, this analysis estimated the proportion of the population with access to an LLIN that slept under one the night before the survey and factors associated with not using an LLIN in households that had achieved universal coverage. METHODS: This was a secondary data analysis using the 2014 malaria indicator survey dataset. The outcome was use of an LLIN among households that achieved universal coverage, while independent variables include age, gender, number of household members, residence, number of sleeping rooms, spraying of rooms with insecticide, number of children under 5 years of age, number of women of child bearing age, relationship structure and community distribution of ant-malarial medicine. RESULTS: Overall, 3361 (62 %) households of the 5345 achieved universal coverage and were included in the analysis giving a total population of 14,450 individuals. Of these, 11,884 (80.10 %) reported to have slept under an LLIN the night before the survey. Children between 6 and 14 years were significantly less likely to use an LLIN when compared to those under 5 years (75.26 vs 83.12 %), [adjusted OR, 1.29 (1.11-1.49), p = 0.001]. The odds of not using an LLIN, significantly increased from households with five members when compared to those that had one member (79.53 vs 84.88 %), [adjusted OR, 2.16 (1.38-3.38), p = 0.001] and rising even further in households with six or more members (78.04 vs 84.88 %), [OR, 2.27 (1.36-3.71), p = 0.003]. CONCLUSIONS: This analysis has showed that 80 % of the population used an LLIN among households that achieved universal coverage following the 2013 mass distribution campaign, especially among children under 5 years, an operational success in this category. However, children between 6 and 14 years and individuals from households with five or more numbers are less likely to use the LLINs. In order to improve usage in these categories, it may require re-focusing the behaviour change communication message to be all-inclusive, especially in era of universal coverage, and to increase the number of LLINs distributed in households with more than four members during future mass distribution campaigns, respectively. PMID- 27267463 TI - Under-representation of frail older people in meta-analysis of dipeptidyl peptidase-4 inhibitors and hypoglycaemia. PMID- 27267464 TI - Kate's Journey: Introducing Students to the Human Side of Aging Services and Supports. AB - Although using novels to teach aging is not a new concept, teaching the human side of long-term services and supports from the perspective of the care recipient via novels has not been thoroughly explored. Literature often reflects societal norms and issues; thus, the use of a novel in the classroom allows for critical reflection and analysis of self and other, particularly when engaging students in aging concepts and experiences of growing old. This article describes the employment of Kate Quinton's Days (1984), a novel that brings into focus the important, and often forgotten, human side of aging services and supports. Additionally, the novel focuses on administrative and medical bureaucracy within the context of home health, and family dynamics that come into play with issues of aging and long-term care. Students may have had limited exposure to various aspects of aging and care that play out in the novel, and bringing the character Kate and her life story into the classroom allows for discussions that would not otherwise be as meaningful or instructive. The authors found that students related in important ways to Kate and went beyond the "system" to consider the lived experience of care and support as we age. PMID- 27267465 TI - Comorbidities and factors associated with central nervous system infections and death in non-perinatal listeriosis: a clinical case series. AB - BACKGROUND: Listeriosis is a rare disease caused by the bacterium Listeria monocytogenes and mainly affects at risk people. Listeriosis can lead to sepsis, central nervous system (CNS) infections and death. The objectives of this study were to describe and quantify comorbidities and neurological sequelae underlying non-perinatal listeriosis cases and to describe the factors associated with death and CNS infections in non-perinatal listeriosis. METHODS: We retrospectively collected clinical data through computerized, paper or microfilmed medical records in two Belgian university hospitals. Logistic regression models and likelihood ratio tests allowed identifying factors associated with death and CNS infections. RESULTS: Sixty-four cases of non-perinatal listeriosis were included in the clinical case series and 84 % were affected by at least one comorbid condition. The main comorbidities were cancer, renal and severe cardio-vascular diseases. Twenty-nine patients (45 %) suffered from a CNS infection and 14 patients (22 %) died during hospitalization, among whom six (43 %) had a CNS involvement. Among surviving patients, eleven suffered from neurological sequelae (22 %) at hospital discharge; all had CNS infection. Five of these patients (45 %) still suffered of their neurological sequelae after a median follow-up of one year (range: 0.08-19). The factor associated with death during the hospitalization was the presence of a severe cardiovascular disease (OR = 4.72, p = 0.015). Two factors inversely related with CNS infections were antibiotic monotherapy (OR = 0.28, p = 0.04) and the presence of renal disease (OR = 0.18, p = 0.02). CONCLUSIONS: In a public health context these results could be a starting point for future burden of listeriosis studies taking into account comorbidity. PMID- 27267466 TI - Cationic liposomes containing antioxidants reduces pulmonary injury in experimental model of sepsis: Liposomes antioxidants reduces pulmonary damage. AB - The intracellular redox state of alveolar cells is a determining factor for tolerance to oxidative and pro-inflammatory stresses. This study investigated the effects of intratracheal co-administration of antioxidants encapsulated in liposomes on the lungs of rats subjected to sepsis. For this, male rats subjected to sepsis induced by lipopolysaccharide from Escherichia coli or placebo operation were treated (intratracheally) with antibiotic, 0.9% saline and antioxidants encapsulated or non-encapsulated in liposomes. Experimental model of sepsis by cecal ligation and puncture (CLP) was performed in order to expose the cecum. The cecum was then gently squeezed to extrude a small amount of feces from the perforation site. As an index of oxidative damage, superoxide anions, lipid peroxidation, protein carbonyls, catalase activity, nitrates/nitrites, cell viability and mortality rate were measured. Infected animals treated with antibiotic plus antioxidants encapsulated in liposomes showed reduced levels of superoxide anion (54% or 7.650+/-1.263 nmol/min/mg protein), lipid peroxidation (33% or 0.117+/-0.041 nmol/mg protein), protein carbonyl (57% or 0.039 +/- 0.022 nmol/mg protein) and mortality rate (3.3%), p value <0.001. This treatment also reduced the level of nitrite/nitrate and increased cell viability (90.7%) of alveolar macrophages. Taken togheter, theses results support that cationic liposomes containing antioxidants should be explored as coadjuvants in the treatment of pulmonary oxidative damage. PMID- 27267467 TI - First detection of Candidatus Rickettsia barbariae in the flea Vermipsylla alakurt from north-western China. AB - BACKGROUND: Vermipsylla is a genus of the family Vermipsyllidae within the order Siphonaptera of fleas. Vermipsylla alakurt is mainly distributed in alpine pastoral areas of Kazakhstan, Mongolia, China and Nepal, and infests sheep, yaks and horses, causing irritation, poor condition, anaemia and even death. However, to date, no rickettsial agents have been reported in V. alakurt. FINDINGS: A total of 133 fleas were collected directly from the tails of three sheep flocks (n = 335) in Minfeng County, Xinjiang Uygur Autonomous Region, north-western China. Of these, 55 fleas were identified by morphological examination and molecular analysis of four loci (the ribosomal 18S and 28S rDNA genes and the mitochondrial genes cytochrome c oxidase subunit II and elongation factor 1 alpha). Eight Rickettsia-specific gene fragments originated from seven genes: the 17-kilodalton antigen gene (17-kDa), citrate synthase gene (gltA), 16S rRNA gene (rrs), outer membrane protein A gene (ompA), surface cell antigen 1 gene (sca1), PS120 protein gene (gene D), and outer membrane protein B gene (ompB, two fragments), were used to identify the species of Rickettsia in 53 fleas. The amplified products were sequenced and included in a phylogenetic analysis to verify the taxonomic identification of the rickettsial agents. Based on morphological and molecular evidence, the flea was identified as Vermipsylla alakurt. Nine samples were positive (16.98 %, 9/53) for Rickettsia spp. The phylogenetic tree revealed that the rickettsial agents found in V. alakurt cluster with Candidatus Rickettsia barbariae. CONCLUSIONS: Our study suggests that: (i) V. alakurt may serve as a carrier for Candidatus R. barbariae; and (ii) Candidatus R. barbariae, previously reported in Israel, is the eighth newly discovered validated Rickettsia species in China. This finding extends our knowledge of the distribution of Candidatus R. barbariae and the profile of carriers, which not only comprise ticks but also fleas. PMID- 27267468 TI - The application of health literacy measurement tools (collective or individual domains) in assessing chronic disease management: a systematic review protocol. AB - BACKGROUND: The term "health literacy" (HL) was first coined in 1974, and its most common definition is currently defined as a person's ability to access, understand, evaluate, communicate, and use health information to make decisions for one's health. The previous systematic reviews assessing the effect of existing HL measurement tools on health outcomes have simply searched for the term "health literacy" only to identify measures instead of incorporating either one or more of the five domains in their search. Furthermore, as the domain "use" is fairly new, few studies have actually assessed this domain. In this protocol, we propose to identify and assess HL measures that applied the mentioned five domains either collectively or individually in assessing chronic disease management, in particular for asthma and chronic obstructive pulmonary disease (COPD). The ultimate goal is to provide recommendations towards the development and validation of a patient-centric HL measurement tool for the two diseases. METHODS/DESIGN: A comprehensive, electronic search will be conducted to identify potential studies dating from 1974 to 2016 from databases such as Embase, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science, ERIC, PsycINFO, and HAPI. Database searches will be complemented with grey literature. Two independent reviewers will perform tool selection, study selection, data extraction, and quality assessment using pre-designed study forms. Any disagreement will be resolved through discussion or a third reviewer. Only studies that have developed or validated HL measurement tools (including one or more of the five domains mentioned above) among asthma and COPD patients will be included. Information collected from the studies will include instrument details such as versions, purpose, underlying constructs, administration, mapping of items onto the five domains, internal structure, scoring, response processes, standard error of measurement (SEM), correlation with other variables, clinically important difference, and item response theory (IRT)-based analyses. The identified strengths and weaknesses as well as reliability, validity, responsiveness, and interpretability of the tools from the validation studies will also be assessed using the COSMIN checklist. A synthesis will be presented for all tools in relation to asthma and COPD management. DISCUSSION: This systematic review will be one of several key contributions central to a global evidence-based strategy funded by the Canadian Institutes of Health Research (CIHR) for measuring HL in patients with asthma and COPD, highlighting the gaps and inconsistencies of domains between existing tools. The knowledge generated from this review will provide the team information on (1) the five-domain model and cross domains, (2) underlying constructs, (3) tool length, (4) time for completion, (5) reading level, and (6) format for development of the proposed tool. Other aspects of the published validation studies such as reliability coefficients, SEM, correlations with other variables, clinically important difference, and IRT-based analyses will be important for comparison purposes when testing, interpreting, and validating the developed tool. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037532. PMID- 27267469 TI - Serglycin proteoglycans limit enteropathy in Trichinella spiralis-infected mice. AB - BACKGROUND: Serglycin proteoglycans are essential for maturation of secretory granules and for the correct granular storage of cationic proteases in hematopoietic cells, e.g. mast cells. However, little is known about the in vivo functions of serglycin proteoglycans during infection. Here we investigated the potential role of serglycin proteoglycans in host defense after infection with the nematode Trichinella spiralis. RESULTS: Twelve days post infection lack of serglycin proteoglycans caused significantly increased enteropathy. The serglycin deficient mice showed significantly increased intestinal worm burden, reduced recruitment of mast cells to the intestinal crypts, decreased levels of the mast cell proteases MCPT5 and MCPT6 in intestinal tissue, decreased serum levels of TNF-alpha, IL-1beta, IL-10 and IL-13, increased levels of IL-4 and total IgE in serum, and increased intestinal levels of the neutrophil markers myeloperoxidase and elastase, as compared to wild type mice. At five weeks post infection, increased larvae burden and inflammation were seen in the muscle tissue of the serglycin-deficient mice. CONCLUSIONS: Our results demonstrate that the serglycin deficient mice were more susceptible to T. spiralis infection and displayed an unbalanced immune response compared to wild type mice. These findings point to an essential regulatory role of serglycin proteoglycans in immunity. PMID- 27267470 TI - The dynamics of fidelity over the time course of long-term memory. AB - Bayesian models of cognition assume that prior knowledge about the world influences judgments. Recent approaches have suggested that the loss of fidelity from working to long-term (LT) memory is simply due to an increased rate of guessing (e.g. Brady, Konkle, Gill, Oliva, & Alvarez, 2013). That is, recall is the result of either remembering (with some noise) or guessing. This stands in contrast to Bayesian models of cognition while assume that prior knowledge about the world influences judgments, and that recall is a combination of expectations learned from the environment and noisy memory representations. Here, we evaluate the time course of fidelity in LT episodic memory, and the relative contribution of prior category knowledge and guessing, using a continuous recall paradigm. At an aggregate level, performance reflects a high rate of guessing. However, when aggregate data is partitioned by lag (i.e., the number of presentations from study to test), or is un-aggregated, performance appears to be more complex than just remembering with some noise and guessing. We implemented three models: the standard remember-guess model, a three-component remember-guess model, and a Bayesian mixture model and evaluated these models against the data. The results emphasize the importance of taking into account the influence of prior category knowledge on memory. PMID- 27267472 TI - Erratum to: 'Point-of-sale cigarette marketing and smoking-induced deprivation in smokers: results from a population-based survey'. PMID- 27267473 TI - Isolation of dengue virus serotype 4 genotype II from a patient with high viral load and a mixed Th1/Th17 inflammatory cytokine profile in South Brazil. AB - BACKGROUND: We report the isolation and characterization of dengue virus (DENV) serotype 4 from a resident of Santa Fe, state of Parana, South Brazil, in March 2013. This patient presented with hemorrhagic manifestations, high viral load and, interestingly, a mixed Th1/Th17 cytokine profile. CASE PRESENTATION: The patient presented with classical dengue symptoms, such as fever, rash, myalgia, arthralgia, and hemorrhagic manifestations including petechiae, gum bleeding and a positive tourniquet test result. A serum sample obtained 1 day after the initial appearance of clinical symptoms was positive for NS1 viral antigen, but this sample was negative for both IgM and IgG against DENV. Dengue virus infection was confirmed by isolation of the virus from C6/36 cells, and dengue virus serotyping was performed via one-step RT-PCR. The infection was confirmed to be caused by a serotype 4 dengue virus. Additionally, based on multiple alignment and phylogeny analyses of its complete genome sequence, the viral strain was classified as genotype II (termed LRV13/422). Moreover, a mixed Th1/Th17 cytokine profile was detected in the patient's serum, and this result demonstrated significant inflammation. Biological characterization of the virus via in vitro assays comparing LRV13/422 with a laboratory-adapted reference strain of dengue virus serotype 4 (TVP/360) showed that LRV13/422 infects both vertebrate and invertebrate cell lines more efficiently than TVP/360. However, LRV13/422 was unable to inhibit type I interferon responses, as suggested by the results obtained for other dengue virus strains. Furthermore, LRV13/422 is the first completely sequenced serotype 4 dengue virus isolated in South Brazil. CONCLUSION: The high viral load and mixed Th1/Th17 cytokine profile observed in the patient's serum could have implications for the development of the hemorrhagic signs observed, and these potential relationships can now be further studied using suitable animal models and/or in vitro systems. PMID- 27267471 TI - Stepped wedge cluster randomised trials: a review of the statistical methodology used and available. AB - BACKGROUND: Previous reviews have focussed on the rationale for employing the stepped wedge design (SWD), the areas of research to which the design has been applied and the general characteristics of the design. However these did not focus on the statistical methods nor addressed the appropriateness of sample size methods used.This was a review of the literature of the statistical methodology used in stepped wedge cluster randomised trials. METHODS: Literature Review. The Medline, Embase, PsycINFO, CINAHL and Cochrane databases were searched for methodological guides and RCTs which employed the stepped wedge design. RESULTS: This review identified 102 trials which employed the stepped wedge design compared to 37 from the most recent review by Beard et al. 2015. Forty six trials were cohort designs and 45 % (n = 46) had fewer than 10 clusters. Of the 42 articles discussing the design methodology 10 covered analysis and seven covered sample size. For cohort stepped wedge designs there was only one paper considering analysis and one considering sample size methods. Most trials employed either a GEE or mixed model approach to analysis (n = 77) but only 22 trials (22 %) estimated sample size in a way which accounted for the stepped wedge design that was subsequently used. CONCLUSIONS: Many studies which employ the stepped wedge design have few clusters but use methods of analysis which may require more clusters for unbiased and efficient intervention effect estimates. There is the need for research on the minimum number of clusters required for both types of stepped wedge design. Researchers should distinguish in the sample size calculation between cohort and cross sectional stepped wedge designs. Further research is needed on the effect of adjusting for the potential confounding of time on the study power. PMID- 27267474 TI - Application of portable online LED UV fluorescence sensor to predict the degradation of dissolved organic matter and trace organic contaminants during ozonation. AB - This work aims to correlate signals of LED UV/fluorescence sensor with the degradation of dissolved organic matter (DOM) and trace-level organic contaminants (TOrCs) during ozonation process. Six sets of bench-scale ozonation kinetic experiments incorporated with three different water matrices and 14 TOrCs of different reactivity (group I ~ V) were conducted. Calibrated by tryptophan and humic substances standards and verified by the lab benchtop spectroscopy, the newly developed portable/online LED sensor, which measures the UV280 absorbance, protein-like and humic-like fluorescence simultaneously, was feasible to monitor chromophores and fluorophores with good sensitivity and accuracy. The liquid chromatography with organic carbon detector combined with 2D synchronous correlation analysis further demonstrated how the DOM components of large molecular weight were transformed into small moieties as a function of the decrease of humic-like fluorescence. For TOrCs, their removal rates were well correlated with the decrease of the LED UV/fluorescence signals, and their elimination patterns were mainly determined by their reactivity with O3 and hydroxyl radicals. At approximately 50% reduction of humic-like fluorescence almost complete oxidation of TOrCs of group I and II was reached, a similar removal percentage (25-75%) of TOrCs of group III and IV, and a poor removal percentage (<25%) of group V. This study might contribute to the smart control of advanced oxidation processes for the water and wastewater treatment in the future. PMID- 27267475 TI - Reductive transformation of carbamazepine by abiotic and biotic processes. AB - The antiepileptic drug carbamazepine (CBZ) is ubiquitously present in the anthropogenic water cycle and is therefore of concern regarding the potable water supply. Despite of its persistent behavior in the aquatic environment, a redox dependent removal at bank filtration sites with anaerobic aquifer passage was reported repeatedly but not elucidated in detail yet. The reductive transformation of CBZ was studied, using abiotic systems (catalytic hydrogenation, electrochemistry) as well as biologically active systems (column systems, batch degradation tests). In catalytic hydrogenation CBZ is gradually hydrogenated and nine transformation products (TPs) were detected by liquid chromatography high-resolution mass spectrometry. 10,11-Dihydro-CBZ ((2H)-CBZ) was the major stable product in these abiotic, surface catalyzed reduction processes and turned out to be not a precursor of the more hydrogenated TPs. In the biotic reduction processes the formation of (2H)-CBZ alone could not explain the observed CBZ decline. There, also traces of (6H)-CBZ and (8H)-CBZ were formed by microbes under anaerobic conditions and four phase-II metabolites of reduced CBZ could be detected and tentatively identified. Thus, the spectrum of reduction products of CBZ is more diverse than previously thought. In environmental samples CBZ removal along an anaerobic soil passage was confirmed and (2H)-CBZ was determined at one of the sites. PMID- 27267476 TI - Iron encapsulated in boron and nitrogen codoped carbon nanotubes as synergistic catalysts for Fenton-like reaction. AB - Iron nanoparticles (NPs) encapsulated in B, N-codoped carbon nanotubes (Fe@C-BN) as heterogeneous Fenton-like catalysts were obtained by a simple and scalable pyrolysis method, and their performances were examined in the oxidative degradation of various organics in the presence of the different oxidants. The results showed that organic dyes can be effectively degraded by Fe@C-BN in the presence of peroxymonosulfate. Calcination temperature and mass of iron salt significantly affected the structures and performances of the catalysts. The effects of several reaction conditions, such as initial dye concentration, oxidant type (peroxymonosulfate, peroxydisulfate, and H2O2) and dosage, initial pH, inorganic anions, reaction temperature and dye types on oxidation as well as the stability of the composite were extensively evaluated in view of the practical applications. Through the investigation of reaction processes, HO(.) and SO4(.-) radicals were identified using quenching experiments. Owing to the synergistic effects between the iron NPs and B, N-doped carbon, Fe@C-BN catalysts intrinsically display an excellent catalytic activity for Fenton-like reaction. This study gives new insights into the design and preparation of iron NPs encapsulated in B, N-codoped carbon nanotubes as an effective strategy to enhance the overall catalytic activity. PMID- 27267477 TI - Halogenated methanesulfonic acids: A new class of organic micropollutants in the water cycle. AB - Mobile and persistent organic micropollutants may impact raw and drinking waters and are thus of concern for human health. To identify such possible substances of concern nineteen water samples from five European countries (France, Switzerland, The Netherlands, Spain and Germany) and different compartments of the water cycle (urban effluent, surface water, ground water and drinking water) were enriched with mixed-mode solid phase extraction. Hydrophilic interaction liquid chromatography - high resolution mass spectrometry non-target screening of these samples led to the detection and structural elucidation of seven novel organic micropollutants. One structure could already be confirmed by a reference standard (trifluoromethanesulfonic acid) and six were tentatively identified based on experimental evidence (chloromethanesulfonic acid, dichloromethanesulfonic acid, trichloromethanesulfonic acid, bromomethanesulfonic acid, dibromomethanesulfonic acid and bromochloromethanesulfonic acid). Approximated concentrations for these substances show that trifluoromethanesulfonic acid, a chemical registered under the European Union regulation REACH with a production volume of more than 100 t/a, is able to spread along the water cycle and may be present in concentrations up to the MUg/L range. Chlorinated and brominated methanesulfonic acids were predominantly detected together which indicates a common source and first experimental evidence points towards water disinfection as a potential origin. Halogenated methanesulfonic acids were detected in drinking waters and thus may be new substances of concern. PMID- 27267478 TI - Crystallisation of minerals from concentrated saline dairy effluent. AB - An understanding of crystallisation within saline effluents is important for the design of both brine crystallisers and brine disposal ponds. In this work, crystallisation of a saline effluent concentrate from the Australian dairy industry has been examined at 22 wt% and 30 wt% total solids and at temperatures between 10 and 70 degrees C. The precipitation occurs more rapidly at higher temperatures. This trend is dictated by precipitation of calcium phosphate salts, albeit the major constituents of the mixture are NaCl and lactose. The crystallisation induction time can be shortened by introducing cavitation induced by ultrasound. In particular, the use of two short acoustic pulses between 3.7 J/g and 16 J/g at 20 kHz spaced ten minutes apart has maximum impact upon both induction time and crystal size. It is believed that the first ultrasound pulse either generates new nuclei or enhances the mass transfer of solute toward the surface of sub-micron growing crystals. Conversely, the second pulse disrupts the growing crystals and forms secondary nuclei. The ultrasound cannot shift the solution equilibrium and so is not able to improve the low crystal yield. To increase this total yield, further evaporation is necessary. The work provides direction to personnel in the dairy industry of the feasibility of brine crystallisation with respect to energy demand and solid recovery. PMID- 27267479 TI - Metagenomic insights into ultraviolet disinfection effects on antibiotic resistome in biologically treated wastewater. AB - High-throughput sequencing-based metagenomic approaches were used to comprehensively investigate ultraviolet effects on the microbial community structure, and diversity and abundance of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) in biologically treated wastewater. After ultraviolet radiation, some dominant genera, like Aeromonas and Halomonas, in the wastewater almost disappeared, while the relative abundance of some minor genera including Pseudomonas and Bacillus increased dozens of times. Metagenomic analysis showed that 159 ARGs within 14 types were detectable in the samples, and the radiation at 500 mJ/cm(2) obviously increased their total relative abundance from 31.68 ppm to 190.78 ppm, which was supported by quantitative real time PCR. As the dominant persistent ARGs, multidrug resistance genes carried by Pseudomonas and bacitracin resistance gene bacA carried by Bacillus mainly contributed to the ARGs abundance increase. Bacterial community shift and MGEs replication induced by the radiation might drive the resistome alteration. The findings may shed new light on the mechanism behind the ultraviolet radiation effects on antibiotic resistance in wastewater. PMID- 27267480 TI - Increases in Cardiac Output and Oxygen Consumption During Enhanced External Counterpulsation. AB - BACKGROUND: Regular enhanced external counterpulsation (EECP) improves exercise capacity possibly through a training effect, but the roles of oxygen consumption (VO2) vs. direct EECP effects (diastolic augmentation, DA-ratio), and their relation to cardiac index (CI) during EECP are unknown. METHODS: We studied eight patients with angina pectoris (median [range] age 72 [53-85], 25% women), who underwent EECP for 35 daily sessions. Before, during and after the first and last sessions, we assessed VO2, DA-ratio and CI. RESULTS: At first EECP, CI increased from 2.2 (1.7-2.9) L/min/m2 prior to EECP to 3.0 (2.2-3.8) during EECP (p=0.011), and returned to 2.4 (0.8-3.0). Similarly, VO2 increased during EECP and returned to baseline after EECP. These patterns were reproduced at the last EECP session. Absolute values of CI and VO2 correlated with each other during but not prior to or after EECP. The increase in CI correlated with the increase in VO2 by trend: (first session, r 0.52, p=0.19; second session r 0.69, p=0.09), but not with DA ratio. CONCLUSIONS: Acutely during EECP, there is an increase in cardiac output that is unrelated to direct EECP effects but related to, and may be secondary to, an increase in peripheral O2 demand. This may represent a training effect. PMID- 27267481 TI - An Unusual Cause of Out-of-Hospital Cardiac Arrest Recorded on a Heartrate Monitor. AB - Coronary vasospasm is an uncommon, but perhaps under-recognised, cause of cardiac arrest. We present a novel case of an exercise-induced out-of-hospital cardiac arrest due to coronary vasospasm, captured on a heartrate monitor, and discuss the management options for this condition. PMID- 27267482 TI - Obituary - Henry Krum. PMID- 27267483 TI - Modified Separator Using Thin Carbon Layer Obtained from Its Cathode for Advanced Lithium Sulfur Batteries. AB - The realization of a practical lithium sulfur battery system, despite its high theoretical specific capacity, is severely limited by fast capacity decay, which is mainly attributed to polysulfide dissolution and shuttle effect. To address this issue, we designed a thin cathode inactive material interlayer modified separator to block polysulfides. There are two advantages for this strategy. First, the coating material totally comes from the cathode, thus avoids the additional weights involved. Second, the cathode inactive material modified separator improve the reversible capacity and cycle performance by combining gelatin to chemically bond polysulfides and the carbon layer to physically block polysulfides. The research results confirm that with the cathode inactive material modified separator, the batteries retain a reversible capacity of 644 mAh g(-1) after 150 cycles, showing a low capacity decay of about 0.11% per circle at the rate of 0.5C. PMID- 27267484 TI - Negative Birefringence in the Higher Homologs of the 5O.m Series of Liquid Crystals. AB - A detailed study of the different parameters of the higher homologs of the 5O.m (m = 14, 16) series of liquid-crystalline compounds is reported. These are interdigitated compounds with unsymmetrical alkyl chain length. The compounds have a unique nature, unlike the other members of the nO.m series. The molecular structure reported in this article is not purely uniaxial; it has a bending tendency. In this article, we report that both the compounds exhibit negative birefringence. For the optical study, the refractive indices, ne and no, of the sample are measured by the thin-prism technique, using a He-Ne laser beam of wavelength 633 nm. A four-parameter model was used for fitting the experimental results. From the experimentally measured refractive indices, it is possible to compare different parameters with those of the theoretical models. PMID- 27267485 TI - A New Method for Treatment of Lymphedema of Limbs: Standardized Manual Massage with a New Device Linforoll in Conservative and Surgical Therapy Protocols. AB - OBJECTIVES: Edema fluid in lymphedematous limbs should be evacuated to sites where it can be absorbed. It should be moved either to the hypogastrium or arm/scapular regions along tissue channels or implanted silicon channels or through lymphovenous anastomoses. For that purpose, the manual lymphatic drainage of limb is an effective method. Standardization of manual massage applied force and timing becomes necessary. AIM: A device with known pressing area and continuously showing the applied force while moving it toward the root of the limb is needed. Moreover, force could be adjusted to the stiffness of the massaged tissues that varies at different levels of the limb. Results from such a device would be repeatable and reproducible by others. METHODS: In this study we present data on tissue fluid hydromechanics obtained from 20 patients with obstructive limb lymphedema during massage with a massaging roller called Linforoll. Linforoll is composed of a hand piece with roller and pressure sensor connected wireless to the computer displaying the pressure curve of the applied force. Electron microscopy studies for checking eventual tissue changes were done. RESULTS AND CONCLUSIONS: Linforoll provides the possibilities of: 1) regulating the applied force according to the hydromechanic conditions of the massaged tissues; 2) standardization of massage repeatable in the same patient; 3) decrease of limb volume; 4) evident increase in tissue elasticity; 5) application as a driving force for fluid flow along the surgically implanted tubing and vessels running to the lymphovenous shunts. PMID- 27267487 TI - Management and Restoration of an Implant With Irreversibly Damaged Internal Threads: A Clinical Report. AB - This report describes a method to restore an implant with irreversibly damaged internal threads. The remaining fractured post from the previous restoration was removed using a combination of an impression coping and an end-cutting bur. An elastomeric impression of the internal surface of the damaged implant, as well as the position of the adjacent implant, was made for fabrication of a new cast post and core and an implant supported 2-unit ceramometal splinted prosthesis. PMID- 27267486 TI - Thresholds for clinical importance for four key domains of the EORTC QLQ-C30: physical functioning, emotional functioning, fatigue and pain. AB - BACKGROUND: The EORTC QLQ-C30 is one of the most widely used quality of life questionnaires in cancer research. Availability of thresholds for clinical importance for the individual questionnaire domains could help to increase its interpretability. The aim of our study was to identify thresholds for clinical importance for four EORTC QLQ-C30 scales: Physical Functioning (PF), Emotional Functioning (EF), Pain (PA) and Fatigue (FA). METHODS: We recruited adult cancer patients from Austria, the Netherlands, Poland and the UK. No restrictions were placed on diagnosis or type or stage of treatment. Patients completed the QLQ-C30 and three anchor items reflecting potential attributes of clinically important levels of PF, EF, PA and FA. We merged the anchor items assessing perceived burden, limitations in daily activities and need for help into a dichotomous external criterion to estimate thresholds for clinical importance using Receiver Operator Characteristic (ROC) analysis. RESULTS: In our sample of 548 cancer patients (mean age 60.6 years; 54 % female), the QLQ-C30 scales showed high diagnostic accuracy in identifying patients reporting burden, limitations and/or need for help related to PF, EF, PA and FA. All areas under the curve were above 0.86. CONCLUSIONS: We were able to estimate thresholds for clinical importance for four QLQ-C30 scales. When used in daily clinical practice, these thresholds can help to identify patients with clinically important problems requiring further exploration and possibly intervention by health care professionals. PMID- 27267488 TI - Parallel and Low-Order Scaling Implementation of Hartree-Fock Exchange Using Local Density Fitting. AB - Calculations using modern linear-scaling electron-correlation methods are often much faster than the necessary reference Hartree-Fock (HF) calculations. We report a newly implemented HF program that speeds up the most time-consuming step, namely, the evaluation of the exchange contributions to the Fock matrix. Using localized orbitals and their sparsity, local density fitting (LDF), and atomic orbital domains, we demonstrate that the calculation of the exchange matrix scales asymptotically linearly with molecular size. The remaining parts of the HF calculation scale cubically but become dominant only for very large molecular sizes or with many processing cores. The method is well parallelized, and the speedup scales well with up to about 100 CPU cores on multiple compute nodes. The effect of the local approximations on the accuracy of computed HF and local second-order Moller-Plesset perturbation theory energies is systematically investigated, and default values are established for the parameters that determine the domain sizes. Using these values, calculations for molecules with hundreds of atoms in combination with triple-zeta basis sets can be carried out in less than 1 h, with just a few compute nodes. The method can also be used to speed up density functional theory calculations with hybrid functionals that contain HF exchange. PMID- 27267489 TI - Health status among urban residents living in proximity to petroleum coke storage: a first examination. AB - We conducted an in-person survey in neighborhoods in south Chicago to examine whether residence near outdoor petroleum coke storage piles was associated with poorer health status and illness symptoms. A total of 223 adults (>=18) completed the surveys in English or Spanish, including 136 from a neighborhood exposed to the petroleum coke and 87 from a nearby comparison neighborhood. Exposure was defined based on prevailing winds and distance. We conducted a propensity score regression analysis, and found that residents in the exposed neighborhood were significantly more likely to report poor self-rated health, more unhealthy physical and mental health days, more illness symptoms including in particular respiratory and neurological symptoms, and worse perceived environmental conditions. The survey is limited by the small sample and the self-report nature of the data, but provides initial quantitative evidence that residence near outdoor petroleum coke storage piles may pose a public health risk. PMID- 27267491 TI - Do memory aids help everyday memory? A controlled trial of a Memory Aids Service. AB - There is a growing body of knowledge about the use of compensatory memory aids in memory rehabilitation, but relatively few controlled trials on how to train the use of such aids. This study investigated the effects of systematic training in the use of compensatory memory aids on everyday memory functioning within a Memory Aids Service. In a controlled clinical trial, a comparison was made between treatment participants and waiting list controls. Participants had everyday memory problems secondary to progressive or non-progressive neurological conditions. Following baseline assessment and goal setting, treatment participants underwent three training sessions, in which memory aids were matched to goals, across a six week period, with a follow-up assessment 12 weeks later. Outcome was measured by a goal attainment diary, neuropsychological test performance, psychosocial questionnaires and a problem solving inventory. There was a significant treatment effect of training on the goal attainment diary but only at 12 weeks follow-up. A post-hoc analysis indicated that treatment was effective for participants with a non-progressive condition but not for participants with a progressive condition. We conclude that a Memory Aids Service can be beneficial for patients with a non-progressive neurological condition, and make suggestions that might inform future applications of memory aids with those who have a progressive neurological disorder. PMID- 27267490 TI - Are cancer-related decision aids appropriate for socially disadvantaged patients? A systematic review of US randomized controlled trials. AB - BACKGROUND: Shared decision-making (SDM) is considered a key component of high quality cancer care and may be supported by patient decision aids (PtDAs). Many patients, however, face multiple social disadvantages that may influence their ability to fully participate in SDM or to use PtDAs; additionally, these social disadvantages are among the determinants of health associated with greater cancer risk, unwarranted variations in care and worse outcomes. The purpose of this systematic review is to describe the extent to which disadvantaged social groups in the United States (US) have been included in trials of cancer-related PtDAs and to highlight strategies, lessons learned and future opportunities for developing and evaluating PtDAs that are appropriate for disadvantaged populations. METHODS: We selected cancer-related US studies from the Cochrane 2014 review of PtDAs and added RCTs meeting Cochrane criteria from searches of PubMed, CINAHL, PsycINFO (January 2010 to December 2013); and reference lists. Two reviewers independently screened titles/abstracts; three reviewers independently screened full text articles, performed data extraction and assessed: 1) inclusion of participants based on seven indicators of social disadvantage (limited education; female gender; uninsured or Medicaid status; non U.S. nativity; non-White race or Hispanic ethnicity; limited English proficiency; low-literacy), and 2) attention to social disadvantage in the development or evaluation of PtDAs. RESULTS: Twenty-three of 39 eligible RCTs included participants from at least one disadvantaged subgroup, most frequently racial/ethnic minorities or individuals with limited education and/or low literacy. Seventeen studies discussed strategies and lessons learned in attending to the needs of disadvantaged social groups in PtDA development; 14 studies targeted disadvantaged groups or addressed subgroup differences in PtDA evaluation. CONCLUSIONS: The diversity of the US population is represented in a majority of cancer-related PtDA RCTs, but fewer studies have tailored PtDAs to address the multiple social disadvantages that may impact patients' participation in SDM. More detailed attention to the comprehensive range of social factors that determine cancer risk, variations in care and outcomes is needed in the development and evaluation of PtDAs for disadvantaged populations. TRIAL REGISTRATION: Registered 24 October 2014 in PROSPERO International prospective register of systematic reviews ( CRD42014014470 ). PMID- 27267492 TI - Turtles as a Possible Reservoir of Nontyphoidal Salmonella in Shanghai, China. AB - Terrapins and turtles are known to transmit Salmonella to humans. However, little was known about the occurrence of this pathogen in soft-shelled terrapin that is a popular delicacy in Chinese and other East Asian cuisines. We isolated and characterized 82 (24.4%) isolates of Salmonella from 336 fecal samples of soft shelled terrapins (51 of 172; 29.7%) and pet turtles (31 of 164; 18.9%) in Shanghai. Salmonella Thompson was the most common serotype (17.1%) among others. Many isolates (84.1%) were resistant to multiple antimicrobials (>=3). Molecular analysis of Salmonella Thompson and Salmonella Typhimurium using pulsed-field gel electrophoresis unveiled a close genetic relationship between several human and terrapin isolates. Our results highlight the risk associated with the handling and consumption of turtles and their role in the spread of Salmonella in the human salmonellosis. PMID- 27267493 TI - Effectiveness of auditory and tactile crossmodal cues in a dual-task visual and auditory scenario. AB - In this study, we examined how spatially informative auditory and tactile cues affected participants' performance on a visual search task while they simultaneously performed a secondary auditory task. Visual search task performance was assessed via reaction time and accuracy. Tactile and auditory cues provided the approximate location of the visual target within the search display. The inclusion of tactile and auditory cues improved performance in comparison to the no-cue baseline conditions. In comparison to the no-cue conditions, both tactile and auditory cues resulted in faster response times in the visual search only (single task) and visual-auditory (dual-task) conditions. However, the effectiveness of auditory and tactile cueing for visual task accuracy was shown to be dependent on task-type condition. Crossmodal cueing remains a viable strategy for improving task performance without increasing attentional load within a singular sensory modality. Practitioner Summary: Crossmodal cueing with dual-task performance has not been widely explored, yet has practical applications. We examined the effects of auditory and tactile crossmodal cues on visual search performance, with and without a secondary auditory task. Tactile cues aided visual search accuracy when also engaged in a secondary auditory task, whereas auditory cues did not. PMID- 27267494 TI - A Fluorescent Polymer Probe with High Selectivity toward Vascular Endothelial Cells for and beyond Noninvasive Two-Photon Intravital Imaging of Brain Vasculature. AB - A chromophore-engineering strategy that relies on the introduction of a ground state distortion in a quadrupolar chromophore was used to obtain a quasi quadrupolar chromophore with red emission and large two-photon absorption (2PA) cross-section in polar solvents. This molecule was functionalized with water solubilizing polymer chains. It constitutes not only a remarkable contrast agent for intravital two-photon microscopy of the functional cerebral vasculature in a minimally invasive configuration but presents intriguing endothelial staining ability that makes it a valuable probe for premortem histological staining. PMID- 27267495 TI - Antithyroid Drugs-The Most Common Treatment for Graves' Disease in the United States: A Nationwide Population-Based Study. PMID- 27267496 TI - Epidemiology of chronic myeloid leukemia in Spain and its possible therapeutic implications. PMID- 27267498 TI - An update on the pharmacotherapeutic interventions for smoking cessation. AB - INTRODUCTION: Cigarette smoking can damage every organ in the body and is the leading known preventable cause of death globally. It is estimated that 70% of patients want to quit, and about 50% report a quit attempt in the past year, yet only 4-7% are successful. These low quit rates represent the importance of appropriate treatment for smoking cessation through behavioral and pharmacotherapeutic means. AREAS COVERED: Pharmacotherapy approximately doubles patients' chances of quitting, and the first-line approved pharmacotherapetuic options include nicotine gum, lozenge, patch, nasal spray, and inhaler, sustained release bupropion, and varenicline. Second-line therapies include nortriptyline and clonidine. Recent evidence suggests a potential role for cytisine and naltrexone. Healthcare providers play an important role in helping patients quit smoking; therefore, a clear understanding of appropriate dosing, regimen, technique, disadvantages, advantages, warnings/precautions, and contraindications for available pharmacotherapeutic options is essential. EXPERT OPINION: To improve chances of success, providers should consider patient preferences and prior experiences with quitting, provide medication-specific counseling for the selected therapy, and encourage adherence with the behavioral and pharmacotherapeutic treatment regimen. PMID- 27267497 TI - Notch1 regulated autophagy controls survival and suppressor activity of activated murine T-regulatory cells. AB - Cell survival is one of several processes regulated by the Notch pathway in mammalian cells. Here we report functional outcomes of non-nuclear Notch signaling to activate autophagy, a conserved cellular response to nutrient stress, regulating survival in murine natural T-regulatory cells (Tregs), an immune subset controlling tolerance and inflammation. Induction of autophagy required ligand-dependent, Notch intracellular domain (NIC) activity, which controlled mitochondrial organization and survival of activated Tregs. Consistently, NIC immune-precipitated Beclin and Atg14, constituents of the autophagy initiation complex. Further, ectopic expression of an effector of autophagy (Atg3) or recombinant NIC tagged to a nuclear export signal (NIC-NES), restored autophagy and suppressor function in Notch1(-/-) Tregs. Furthermore, Notch1 deficiency in the Treg lineage resulted in immune hyperactivity, implicating Notch activity in Treg homeostasis. Notch1 integration with autophagy, revealed in these experiments, holds implications for Notch regulated cell-fate decisions governing differentiation. PMID- 27267499 TI - Reduced rat plasma lysophosphatidylglycerol or lysophosphatidic acid level as a biomarker of aristolochic acid-induced renal and adipose dysfunctions. AB - AIMS: Food products and diet pills containing aristolochic acid (AA) are responsible for a rapid progression of nephropathy associated with reduced body weight in human beings. In this study, we investigated the relationship of dietary NaCl and lysophospholipid (LPL) plasma levels to body weight gain in AA treated rats. MAIN METHODS: Male rats receiving a salt-deficient chow, normal salt chow or high salt chow were injected intraperitoneally daily with AA for 15days. Body weight, visceral fat mass, food intake, levels of LPL in plasma and its synthesized enzyme were investigated. KEY FINDINGS: Body weight gain, visceral fat mass and daily food intake were smaller in AA-treated rats than those of control rats, regardless of dietary salt concentration. AA treatment decreased plasma levels of major lysophosphatidic acid (LPA) molecular species in rats fed the normal or high-salt chow but not the salt-deficient chow, whereas both the plasma lysophospholipase D activity and kidney mRNA level of autotaxin of AA-treated rats fed chow with defined salt concentrations were lower than those of control rats. Plasma levels of major molecular species of lysophosphatidylglycerol (LPG) in AA-treated rat groups fed chow with defined salt concentrations were lower than those of control rats. SIGNIFICANCE: Plasma levels of LPG and LPA seem to be relevant to the reduced body weight gain and fat mass due to AA treatment. PMID- 27267500 TI - The relationship of body image with symptoms of depression and anxiety in patients with anorexia nervosa during outpatient psychotherapy: Results of the ANTOP study. AB - Body image disturbance represents a central characteristic of anorexia nervosa (AN). Depression and anxiety are the most common mental comorbidities in patients with AN. This study aims to investigate the relationship of body image with symptoms of depression and anxiety during outpatient psychotherapy in AN. Analyses were conducted using the data set of the Anorexia Nervosa Treatment Outpatient Study (ANTOP) randomized controlled trial. The ANTOP study included N = 242 females with AN between 18 and 56 years of age. The trial was designed to compare enhanced cognitive behavioral therapy (CBT-E) and focal psychodynamic therapy (FPT) with optimized treatment as usual (TAU-O) for patients with AN. The analyses on body image dimensions were conducted using measures of correlations and multiple linear regression analyses to assess the relationship and longitudinal prediction of symptoms of depression and anxiety by body image dimensions. Results showed that body image perceptions were significantly associated with symptoms of depression and anxiety in patients with AN at all treatment stages. In addition, body image dimensions at early treatment stages predict depression and anxiety in follow-up measurements. The correlation of symptoms of depression and anxiety by body image perceptions increased along treatment course. The persistence of body image disturbance, while body mass index increases under treatment (persistency effect), may constitute a relevant factor contributing to the course of the most common affective comorbidities of depression and anxiety in patients with AN. Body image disturbances in patients with AN should therefore be explicitly targeted within the specialized psychotherapy of affected patients. (PsycINFO Database Record PMID- 27267501 TI - Therapeutic interventions in the treatment of eating disorders: A naturalistic study. AB - This study used naturalistic data from psychodynamic (PD) and cognitive behavioral (CB) clinicians in the community to offer a portrait of treatments for eating disorder (ED) patients as provided in everyday clinical practice. The research aims were (1) to examine the therapeutic interventions reported by PD and CB clinicians working with ED patients; and (2) to assess the impact of different variables (such as patient personality styles, ED symptomatology, and therapists' theoretical orientation and experience) on the technique use reported by clinicians. A national sample of PD and CB clinicians (N = 105) completed the Shedler-Westen Assessment Procedure-200 (SWAP-200; Westen & Shedler, 1999a, 1999b) to assess personality disorders of a female patient with EDs in their care, as well as the Comparative Psychotherapy Process Scale-Bulimia Nervosa (CPPS-BN; Thompson-Brenner & Westen, 2005) to describe the characteristic interventions used in their treatments. Results showed that PD clinicians tended to use primarily PD interventions, while CB clinicians employed CB techniques supplementing them with a wider range of PD strategies. However, clinicians from both theoretical orientations used adjunctive treatment techniques for EDs at a similar level. In addition, use of PD interventions was strongly associated with the personality styles of ED patients regardless of therapists' orientation, primarily being used more often when patients exhibited dysregulated and impulsive styles. Conversely, use of CB interventions was primarily related to a clinicians' CB orientation, patients with more explicit symptoms of anorexia nervosa, and negatively related to clinicians' years of experience. The clinical implications of these findings were discussed. (PsycINFO Database Record PMID- 27267502 TI - Relationship-focused therapy for bulimia and binge eating: Introduction to the special section. AB - Individuals with bulimia nervosa and binge eating disorder commonly report co occurring interpersonal problems, and treatment that focuses on relationships and relational functioning has shown benefit relative to other forms of treatment. Relational psychotherapy for eating disorders can vary on several important dimensions, such as how structured and symptom-focused versus exploratory and patient-directed it is, whether it focuses on past relationships and patterns in relationships over time versus focusing on current relationships, and whether it includes the relationship with the therapist as an explicit topic of conversation and mechanism for relational change. The cases in this special section provide the opportunity to closely compare 3 therapeutic approaches on each of these dimensions. Psychoanalytic Psychotherapy for Bulimia Nervosa, Integrative Dynamic Therapy for Bulimia Nervosa, and Interpersonal Psychotherapy for the Prevention of Weight Gain and Eating Disorders are each highly distinct approaches. The authors of each case explain the intended mechanisms of treatment response, the measures that assess changes in eating disorder symptoms as well as the mechanisms of change, and provide extensive excerpts from case material to demonstrate and illustrate the particular evidence-based treatment. Therapists and researchers may usefully consider the process and outcome variables described in these interpersonal approaches. (PsycINFO Database Record PMID- 27267503 TI - Interpersonal psychotherapy for the prevention of excess weight gain and eating disorders: A brief case study. AB - This article presents a brief case study of "Jane Doe," a 13-year-old, non Hispanic White girl 2 participating in a clinical research trial of interpersonal psychotherapy-weight gain (IPT-WG). Girls at-risk for adult obesity and binge eating disorder (BED) were randomly assigned to take part in 12 weeks of preventative group treatment. Jane's IPT-WG group included five other early adolescent girls (mostly aged 12-13) at risk for adult obesity and BED. The case of Jane illustrates a successful example of IPT-WG for the prevention of excessive weight gain and for the prevention of BED. (PsycINFO Database Record PMID- 27267504 TI - Integrative dynamic therapy for bulimia nervosa: An evidence-based case study. AB - Both cognitive-behavioral therapy (CBT) and psychodynamic psychotherapy are commonly used to treat eating disorders. To further investigate the effectiveness of integrative dynamic therapy (IDT) for bulimia nervosa (BN), our research group undertook a randomized, controlled pilot study comparing IDT with CBT for BN. The case described here was selected from a sample of N = 38 female patients with the symptoms of BN who enrolled in the study. IDT incorporated aspects of the first 4 week stage of CBT, including psychoeducation, self-monitoring, and regular eating. Subsequently, the treatment focused on emotional expression, emotion regulation (defenses), intrapsychic conflict, and interpersonal relationships. The objectives of the report are to demonstrate the effectiveness of an integrative approach to the treatment of eating disorders to address the symptoms of BN and personality issues using pre-, mid-, and posttreatment data, and to illustrate the patient and clinician reactions to each approach to treatment using excerpts from session transcripts and alliance data. (PsycINFO Database Record PMID- 27267505 TI - Psychoanalytic psychotherapy with a client with bulimia nervosa. AB - This case study presents the progress of one patient with bulimia nervosa who was originally very compromised in psychological domains that are the focus of analytic treatment, and includes in-session therapeutic process and a range of outcomes, for example, eating disorder symptoms, attachment status, and reflective functioning. Nested in a study showing more rapid behavioral improvement in subjects receiving cognitive behavior therapy than in subjects receiving psychoanalytic psychotherapy, the case highlights the importance of supplementing RCTs with single case studies and the need of adapting the therapeutic approach as well as the current therapeutic dialogue to the individual client. (PsycINFO Database Record PMID- 27267506 TI - Relationship-focused psychotherapies for eating disorders come of age. AB - This is a commentary on 3 case studies of relationship-focused therapies for eating disorders. The 3 approaches vary along a number of dimensions, but nevertheless share important similarities especially related to the role played by variables such as interpersonal problems and affect dysregulation. I briefly review research on interpersonal- and attachment-based models of eating disorders that provide the evidence-base for theories of therapy that are relationship focused. The Interpersonal Psychotherapy case presented by Tanofsky-Kraff, Shomaker, Young, and Wilfley (2016) illustrates how a group context can facilitate change in key role disputes and role transitions in an adolescent at risk of developing an eating disorder later in her life. The Integrative-Dynamic Therapy case presented by Richards, Shingleton, Goldman, Siegel, and Thompson Brenner (2016) is a novel sequential combination of cognitive-behavioral therapy followed by dynamic psychotherapy for a young adult with bulimia nervosa that likely reflects what most clinicians do in everyday practice. The Psychoanalytic Psychotherapy case presented by Lunn, Poulsen, and Daniel (2016) of a patient with severe personality pathology demonstrates how treatments for eating disorders sometimes must address complex attachment dysfunction, self organization, and therapist countertransference in order to provide a useful therapeutic experience. Relationship-focused theories and therapies for eating disorders have come a long way over the past decades, thus providing therapists with a wider range of approaches that can be truly personalized to their clients. (PsycINFO Database Record PMID- 27267507 TI - Improving psychotherapy for anorexia nervosa: Introduction to the special section on innovative treatment approaches. AB - The available forms of psychotherapy for anorexia nervosa (AN) are helpful to many patients; however, a substantial proportion of adults with AN continues to show persistent symptoms and medical risks following treatment. Clinical investigators are therefore developing innovative adjunctive treatments for adults, to augment treatment effects. The 3 cases in this special section each demonstrate a creative, potent adjunctive treatment approach: Exposure and Response Prevention, Cognitive Remediation Therapy, and Unified Couples Therapy. In addition to demonstrating the treatment and response, the authors also discuss the important opportunities and struggles associated with the experience of providing each treatment for AN. Because adults with AN are often very attached to symptoms, and afraid of change, it is crucial to develop a basis for the therapeutic alliance and motivation to change. In these detailed, vivid, evidence based case examples, the authors demonstrate highly distinct, innovative approaches to these issues. (PsycINFO Database Record PMID- 27267508 TI - Overcoming fear of eating: A case study of a novel use of exposure and response prevention. AB - Even after successful weight restoration, many patients with anorexia nervosa (AN) continue to exhibit maladaptive eating including repetitive behaviors (i.e., food rituals) used to decrease anxiety about food, and to describe fears related to food content, including its effect on shape and weight. Although there are important differences between eating disorders and anxiety disorders, the shared clinical phenomena suggest potentially useful overlap in treatment strategies. This case study will describe treatment of a woman with AN using Exposure and Response Prevention for Anorexia Nervosa (AN-EXRP) as an adjunct to concurrent inpatient treatment. This is a novel use of a treatment approach with established efficacy in the treatment of anxiety disorders. AN-EXRP specifically targets eating-related anxiety with the intent to improve the restrictive eating patterns that persist after acute weight restoration. The case study described includes descriptions of (a) the treatment rationale and its phases of implementation, (b) illustrative sample dialogue between the patient and therapist, (c) pre- and posttreatment data on outcome measures of interest (e.g., food intake at a laboratory meal, self-report anxiety ratings, self-report eating-related rituals, and preoccupations), and (d) therapist considerations (e.g., maintaining alliance, adhering to treatment frame). (PsycINFO Database Record PMID- 27267509 TI - Cognitive remediation therapy and cognitive behavioral therapy with an older adult with anorexia nervosa: A brief case report. AB - Cognitive remediation therapy represents a new approach to the treatment of anorexia nervosa (AN) emerging from research, suggesting that adults with chronic AN have specific neurocognitive inefficiencies. Specifically, adults with AN demonstrate an overly detailed cognitive processing bias (Roberts, Tchanturia, & Treasure, 2013) and difficulties shifting set quickly and efficiently (Roberts, Tchanturia, Stahl, Southgate, & Treasure, 2007). These characteristics manifest as rigid, rule-bound, and detail-focused cognitions, beliefs, and behaviors. Versions of these problems appear to persist after weight restoration (Tchanturia et al., 2004) and are observable in patient's healthy sisters (Roberts et al., 2013). Thus, central coherence difficulties and set-shifting problems have been proposed as endophenotypes and maintaining factors of AN (Roberts et al., 2013). (PsycINFO Database Record PMID- 27267511 TI - Anorexia nervosa in adults: The urgent need for novel outpatient treatments that work. AB - Anorexia nervosa (AN) is a serious psychiatric disorder that often follows a protracted course, and continues to confound those who attempt treatment once the patient has reached adulthood. Several randomized clinical trials for adults with AN have tested well-known therapies such as cognitive behavior therapy, supportive psychotherapies, or focal psychodynamic therapy, all of which have delivered frustratingly few helpful treatment strategies. Perhaps a different path could be pursued where we do not aim to cure all patients with 1 or 2 of these well-trodden therapies. Instead, a more targeted alternative, testing several novel approaches, could collectively reach a larger cohort of patients suffering from AN, the most lethal of all psychiatric disorders. (PsycINFO Database Record PMID- 27267512 TI - Mechanisms of Sb(III) Photooxidation by the Excitation of Organic Fe(III) Complexes. AB - Organic Fe(III) complexes are widely distributed in the aqueous environment, which can efficiently generate free radicals under light illumination, playing a significant role in heavy metal speciation. However, the potential importance of the photooxidation of Sb(III) by organic Fe(III) complexes remains unclear. Therefore, the photooxidation mechanisms of Sb(III) were comprehensively investigated in Fe(III)-oxalate, Fe(III)-citrate and Fe(III)-fulvic acid (FA) solutions by kinetic measurements and modeling. Rapid photooxidation of Sb(III) was observed in an Fe(III)-oxalate solution over the pH range of 3 to 7. The addition of tert-butyl alcohol (TBA) as an .OH scavenger quenched the Sb(III) oxidation, suggesting that .OH is an important oxidant for Sb(III). However, the incomplete quenching of Sb(III) oxidation indicated the existence of other oxidants, presumably an Fe(IV) species in irradiated Fe(III)-oxalate solution. In acidic solutions, .OH may be formed by the reaction of Fe(II)(C2O4) with H2O2, but a hypothetical Fe(IV) species may be generated by the reaction of Fe(II)(C2O4)2(2-) with H2O2 at higher pH. Kinetic modeling provides a quantitative explanation of the results. Evidence for the existence of .OH and hypothetical Fe(IV) was also observed in an irradiated Fe(III)-citrate and Fe(III)-FA system. This study demonstrated an important pathway of Sb(III) oxidation in surface waters. PMID- 27267510 TI - Couple-based interventions in the treatment of adult anorexia nervosa: A brief case example of UCAN. AB - Adult anorexia nervosa (AN) is a serious and often fatal illness that significantly erodes quality of life for both the patient and loved ones. Treatment of adults with AN has focused largely on individual therapy, with recent findings suggesting that improvement is limited and dropout rates are high. In an effort to improve treatment response, we developed a couple-based intervention, Uniting Couples in the treatment of Anorexia Nervosa (UCAN) as an adjunct treatment to standard multidisciplinary care. UCAN leverages the support of a partner and the relationship in treatment by decreasing avoidance around AN, teaching the couple how to effectively address the eating disorder, and helping to foster a more satisfying relationship. This paper presents a case study of a couple who completed UCAN, "Laura and Steve," including their experiences in treatment and outcome measures at pretest, posttest, and 3-month follow-up. Laura showed clinically significant change on the Restraint subscale of the Eating Disorders Examination at follow-up, and both partners showed clinically significant improvements in relationship satisfaction, as well as on self reported and observed communication. Both partners reported very high satisfaction with the treatment. A discussion of therapists' experiences in delivering UCAN is provided, including common challenges for therapists with primarily a couple therapy or an individual CBT for eating disorders background, as well as important factors for therapists to consider in order to optimally leverage the benefits of including partners in treatment for AN. (PsycINFO Database Record PMID- 27267513 TI - Depression and performance on the Repeatable Battery for the Assessment of Neuropsychological Status. AB - There is strong evidence that depression is associated with neuropsychological deficits across multiple domains. However, research on this topic has spanned a variety of measures with different psychometric properties and normative samples, which prevents drawing definitive conclusions about the pattern of neuropsychological deficiencies. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a brief neurocognitive battery that is routinely used in clinical settings and provides co-normed measures of attention, language, memory, and visuospatial/constructional skills. The present study examined the association between depression and RBANS performance in a sample of 66 18-65 year-old adults who completed a neuropsychological evaluation at an outpatient clinic. Results indicated that depressed participants, relative to controls, demonstrated poorer performance in immediate and delayed memory, attention, and visuospatial/constructional abilities, and the four domains were diminished to a similar degree. These results were replicated using a continuous measure of depression symptoms. In addition, the association between depression and delayed memory was at least partially due to current psychotropic medication. The present study suggests that the RBANS is sensitive to the neuropsychological deficits typically found in depression, such that mild to moderate depression in adult outpatients is associated with comparable deficits in attention, memory, and visuospatial/constructional abilities. PMID- 27267515 TI - FDA Approves Drug Combo for Kidney Cancer. AB - The FDA has approved the combination of lenvatinib and everolimus to treat advanced or metastatic renal cell carcinoma. The approval marks the first time that tyrosine kinase and mTOR inhibitors have been combined successfully as second-line treatment for renal cell carcinoma following prior VEGF-targeted therapy. PMID- 27267514 TI - Effect of Transplant on Platelet Function Markers (P-Selectin and Platelet Aggregation) and Adiponectin in Renal Transplant Patients. AB - OBJECTIVES: In chronic kidney disease, both bleeding and thrombotic complications are observed, although with expected recovery after a successful transplant. Adiponectin has protective properties with respect to atherogenesis and inflammation. Plasma adiponectin levels are markedly elevated among patients with end-stage renal disease and are lower after kidney transplant. However, this topic is still debated in the literature. Here, we evaluated the effect of transplant on platelet function markers (P-selectin and platelet aggregation) and adiponectin in renal transplant patients. MATERIALS AND METHODS: Our study included 14 renal transplant patients. Preoperative and week 1, month 1, month 6, year 1, and year 2 samples after transplant were studied. In addition to plasma adiponectin, P-selectin levels, and platelet aggregation tests, biochemical tests and coagulation parameters were also studied. RESULTS: We observed a significant decrease in adiponectin levels 2 years after transplant. Platelet function tests with ADP and collagen were significantly improved, and no changes in P-selectin, ristocetin, and epinephrine levels were observed. CONCLUSIONS: According to our findings, glomerular filtration rate has an important effect on platelet function, but adiponectin levels became normal only in the second year after transplant. Late improvement of low-density lipoprotein cholesterol and adiponectin after transplant suggested to us that patients with kidney transplant may still have risk of cardiovascular events, especially in the first years. PMID- 27267516 TI - BGB-283 Deemed Effective in Phase I Study. AB - In a phase I trial, BGB-283, which targets the RAF family of proteins, was found to be safe and tolerable-and effective-in treating patients with a variety of solid tumors harboring mutations in BRAF, KRAS, and NRAS. PMID- 27267517 TI - Frequency of abnormal T-cells in hypereosinophilic syndrome and hypereosinophilia of undetermined significance- Extended follow-up. PMID- 27267519 TI - Rheumatoid arthritis and metabolic syndrome. PMID- 27267518 TI - Sino nasal inhalation of isotonic versus hypertonic saline (6.0%) in CF patients with chronic rhinosinusitis - Results of a multicenter, prospective, randomized, double-blind, controlled trial. AB - BACKGROUND: Chronic rhinosinusitis is a hallmark of Cystic fibrosis (CF) impairing the patients' quality of life and overall health. However, therapeutic options have not been sufficiently evaluated. Bronchial inhalation of mucolytic substances is a gold standard in CF therapy. Previously, we found that sinonasal inhalation of dornase alfa as vibrating aerosol reduces symptoms of chronic rhinosinusitis more effectively than NaCl 0.9% (net treatment benefit: -5.87+/ 2.3 points, p=0.017; SNOT-20 total score). This multicenter study compares the effect of NaCl 6.0% vs. NaCl 0.9% following the protocol from our preceding study with dornase alfa. METHODS: Sixty nine CF patients with chronic rhinosinusitis in eleven German CF centers were randomized to receive sinonasal vibrating inhalation of either NaCl 6.0% or NaCl 0.9% for 28days. After 28days of wash-out, patients crossed over to the alternative treatment. The primary outcome parameter was symptom score in the disease-specific quality of life Sino-Nasal Outcome Test 20 (SNOT-20). Additionally, pulmonary function was assessed, as well as rhinomanometry and inflammatory markers in nasal lavage (neutrophil elastase, interleukin (IL)-1beta, IL-6, and IL-8) in a subgroup. RESULTS: Both therapeutic arms were well tolerated and showed slight improvements in SNOT-20 total scores (NaCl 6.0%: -3.1+/-6.5 points, NaCl 0.9%: -5.1+/-8.3 points, ns). In both treatment groups, changes of inflammatory parameters in nasal lavage from day 1 to day 29 were not significant. We suppose that the irritating properties of NaCl 6.0% reduced the suitability of the SNOT-20 scores as an outcome parameter. Alternative primary outcome parameters such as MR-imaging or the quantity of sinonasal secretions mobilized with both saline concentrations were, however, not feasible. CONCLUSION: Sinonasal inhalation with NaCl 6.0% did not lead to superior results vs. NaCl 0.9%, whereas dornase alfa had been significantly more effective than NaCl 0.9%. PMID- 27267520 TI - Electrocardiographic changes in dermatomyositis and polymyositis. AB - INTRODUCTION: Cardiac involvement is frequent in inflammatory myopathies. Electrocardiogram (ECG) may show evidence of this involvement and its changes should be well-known and described. OBJECTIVES: Due to the lack of studies in the literature, we conducted an analysis of the ECG findings in patients with dermatomyositis (DM) and polymyositis (PM), comparing them with a control group. METHODS: This cross-sectional study compared the ECG of 86 individuals with no rheumatic disorders (controls) with 112 patients (78 DM and 34 PM), during 2010 2013. The ECG findings between DM and PM were also compared. RESULTS: Demographic characteristics, comorbidities and ECG abnormalities were similar between controls and patients (p>0.05), except for a higher frequency of left ventricular hypertrophy (LVH) in patients (10.7% vs. 1.2%, p=0.008). Demographic characteristics, comorbidities, clinical and laboratory manifestations, were also similar between the groups PM and DM, except for the presence of cutaneous lesions only in DM. One-third of the patients had ECG abnormalities, which were more prevalent in PM than DM (50% vs. 24.4%, p=0.008). LVH, left atrial enlargement, rhythm and conduction abnormalities were more frequent in PM than DM (p<0.05 for all), especially the left anterior fascicular block. CONCLUSIONS: We showed distinct ECG changes between DM and PM and a higher frequency of LVH in patients compared to controls. Investigation of cardiac involvement should be considered even in asymptomatic patients, especially PM. Further studies are necessary in order to determine the correlation of ECG findings with other complementary tests, clinical manifestations, disease activity and progression to other cardiac diseases. PMID- 27267521 TI - Retroperitoneal fibrosis: case series of five patients and review of the literature. AB - Chronic periaortitis (CP) is an umbrella term used to describe a group of nosologically allied conditions that include idiopathic retroperitoneal fibrosis (Ormond's disease), inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis. Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighboring structures-ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Here we describe a 5 years follow-up (2006-2011) of 5 patients admitted to our hospital with symptoms, laboratory, imaging and pathologic finding compatible with retroperitoneal fibrosis. We review our clinical course of our patient with respect to the literature. PMID- 27267522 TI - Food intake assessment and quality of life in women with fibromyalgia. AB - OBJECTIVE: To compare the food intake of women with and without fibromyalgia and verify if the food intake of patients with fibromyalgia interferes with the pain and quality of life. METHODS: Study participants were women with fibromyalgia (FM) seen in Fibromyalgia Outpatient Clinic, Hospital das Clinicas/UFPR and a control group (CT) with healthy women. Data collection was conducted from March to October 2012. For the assessment of food intake we used the Food Registration and the analyzed items were total calories, carbohydrates, proteins, lipids, vitamins (A, C, B12, D and E) and minerals (folate, selenium, zinc, iron, calcium and magnesium). The software used was Avanutri Online((r)). To evaluate the quality of life, the Fibromyalgia Impact Questionnaire (FIQ) and pain threshold were used. RESULTS: 43 patients with FM and 44 healthy women were evaluated. CT group showed a mean consumption of nutrients greater than FM group except for iron. However, only caloric intake, carbohydrates, proteins and lipids in grams and percentage of lipids, vitamin A, E, B12, folate, selenium and calcium were statistically significant. In FM group, there was a negative correlation between vitamin E and FIQ and a positive correlation between percentage of protein and pain threshold. CONCLUSION: Women with FM showed a lower qualitative and quantitative intake in comparison with CT group. Only vitamin E correlated with quality of life and percentage of protein in the diet with sensation of pain. PMID- 27267523 TI - Osteoporosis in primary care: an opportunity to approach risk factors. AB - INTRODUCTION: Climacteric women are susceptible to a number of changes, among them osteoporosis. Osteoporosis is a disease characterized by low bone mass and susceptibility to fracture. Currently, this disease is a public health issue, being necessary to recognize its risk factors. OBJECTIVES: Identify risk factors related to osteoporosis in women attending PROPIS/PROEX/UFMA, tracing a socio demographic characterization and considering community lifestyles. MATERIAL AND METHODS: This is a transversal retrospective clinical with a quantitative approach study conducted between March and June 2013 in Sao Luis-MA with 107 women treated at the Programa de Praticas de Integralidade em Saude (PROPIS - Integrality Health Practice Program). The study was approved by the University Hospital Ethics Committee of UFMA under opinion no. 362/07. Data were tabulated and analyzed in the epidemiological Epi-Info((r)) software, version 3.4.1. RESULTS: The brown color was predominant, consensual relationships proved to be a protective factor and low education was a risk factor. The average age of the group with menopause was 54.1 years and without menopause was 31.3 years (p<0.0001). The average age of menopause was 43.7 years. The irregular menstrual cycle was a protective factor. The average number of pregnancies was 4.56 for the group with menopause and 2.45 for the group without menopause, with most births occurring normally (p<0.0001). Smoking, physical inactivity and caffeine intake were risk factors, while the absence of alcoholism and of soda intake were protective factors for the disease. CONCLUSION: The patients followed the socioeconomic and demographic profile of Maranhao. Most had menarche and menopause in appropriate periods, showed no positive family history of osteoporosis, did not usually drink alcohol, were sedentary and the caffeine intake was high. PMID- 27267524 TI - Metabolic syndrome in patients with rheumatoid arthritis followed at a University Hospital in Northeastern Brazil. AB - INTRODUCTION: Patients with rheumatoid arthritis (RA) are 30-60% more likely to develop cardiovascular disease (CV) than the general population. Metabolic syndrome (MS), defined by a number of cardiovascular risk factors, confers a greater risk of CVdisease and diabetes. The association of MS with RA is not yet fully understood and its prevalence varies from 19 to 63% across studies. OBJECTIVES: To assess the prevalence of MS in a population of RA patients followed in a hospital in Northeastern Brazil and analyze associations of demographic and clinical factors with MS. METHODS: Outpatients with RA were evaluated in a cross-sectional study regarding demographic, clinical, laboratory and anthropometric data. The criteria for defining MS were those adopted by NCEPIII (2005) and IDF (2006). RESULTS: 110 patients with RA were studied; 97.3% were female, with a mean age of 55.5 years (SD=12.9) and duration of illness of 11.2 years (SD=7.3). The MS prevalence from NCEPIII (2005) and IDF (2005) were, respectively, 50% and 53.4%. Advanced age (57.9+/-11.9 versus 52.9+/-13.5; p=0.04) and smoking load >20 packs/year (29% versus 9%, p=0.008) were associated with MS. The major components of the metabolic syndrome were abdominal obesity (98.1%), hypertension (80%) and low HDL cholesterol (72.2%). CONCLUSIONS: RA patients in a tertiary center in Northeastern Brazil showed high prevalence of MS. It is worth noting that almost all patients had MS and abdominal obesity, which has important practical implications. In addition to the components of MS, age and smoking were associated with this syndrome. PMID- 27267525 TI - Comparative study of functional capacity and quality of life among obese and non obese elderly people with knee osteoarthritis. AB - INTRODUCTION: The association between osteoarthritis (OA) and obesity can lead to a reduced functional capacity, compromising the quality of life (QoL) of the elderly. OBJECTIVE: To compare the functional capacity and QoL of obese and non obese older adults with knee OA. METHODS: The sample consisted of 35 subjects with OA divided into two groups, obese and non-obese subjects, according to their body mass index. To assess functional capacity, performance tests such as Timed Up and Go (TUG), gait speed test, and the six-minute walk test (6 MWT) were carried out. To assess QoL, WOMAC and SF-36 questionnaires were administered. We performed descriptive and inferential statistics using SPSS software version 20.0. RESULTS: Elderly patients with OA were divided into two groups (obese, n=16; non-obese, n=19). Socio-demographic characteristics were similar between groups (p>0.05). The obese group showed a worst performance in TUG, brisk walking speed and 6 MWT. A more severe pain was found in the following items: "performing heavy housework chores", "going down stairs", "bending to floor" and "getting up from bed" in the obese group (p<0.05). In addition, the obese group had more difficulty to perform tasks for the following items: "going down stairs", "rising from a chair", "standing" and "getting on/off toilet" (p<0.05). There was no statistically significant difference in the assessed domains of SF-36 between groups (p>0.05). CONCLUSION: OA associated with obesity caused a negative impact on functional capacity; however, quality of life scores were low, and no difference in obese and non-obese subjects was found. PMID- 27267526 TI - Indirect and direct costs of treating patients with ankylosing spondylitis in the Brazilian public health system. AB - INTRODUCTION: Patients with ankylosing spondylitis require a team approach from multiple professionals, various treatment modalities for continuous periods of time, and can lead to the loss of labour capacity in a young population. So, it is necessary to measure its socio-economic impact. OBJECTIVES: To describe the use of public resources to treat AS in a tertiary hospital after the use of biological medications was approved for treating spondyloarthritis in the Health Public System, establishing approximate values for the direct and indirect costs of treating this illness in Brazil. MATERIAL AND METHODS: 93 patients selected from the ambulatory spondyloarthritis clinic at the Hospital de Clinicas of the Federal University of Parana between September 2011 and September 2012 had their direct costs indirect treatment costs estimation. RESULTS: 70 patients (75.28%) were male and 23 (24.72%) female. The mean age was 43.95 years. The disease duration was calculated based on the age of diagnosis and the mean was 8.92 years (standard deviation: 7.32); 63.44% were using anti-tumour necrotic factor drugs. Comparing male and female patients the mean Bath Ankylosing Spondylitis Disease Activity Index was 4.64 and 5.49 while the mean Bath Ankylosing Spondylitis Functional Index was 5.03 and 6.35 respectively. CONCLUSIONS: The Brazilian public health system's spending related to ankylosing spondylitis has increased in recent years. An important part of these costs is due to the introduction of new, more expensive health technologies, as in the case of nuclear magnetic resonance and, mainly, the incorporation of anti-tumour necrotic factor therapy into the therapeutic arsenal. The mean annual direct and indirect cost to the Brazilian public health system to treat a patient with ankylosing spondylitis, according to our findings, is US$ 23,183.56. PMID- 27267527 TI - Assessment of cardiovascular risk in patients with rheumatoid arthritis using the SCORE risk index. AB - INTRODUCTION: Rheumatoid arthritis is an autoimmune disease that causes systemic involvement and is associated with increased risk of cardiovascular disease. OBJECTIVE: To analyze the prediction index of 10-year risk of a fatal cardiovascular disease event in female RA patients versus controls. METHODS: Case control study with analysis of 100 female patients matched for age and gender versus 100 patients in the control group. For the prediction of 10-year risk of a fatal cardiovascular disease event, the SCORE and modified SCORE (mSCORE) risk indexes were used, as suggested by EULAR, in the subgroup with two or more of the following: duration of disease >=10 years, RF and/or anti-CCP positivity, and extra-articular manifestations. RESULTS: The prevalence of analyzed comorbidities was similar in RA patients compared with the control group (p>0.05). The means of the SCORE risk index in RA patients and in the control group were 1.99 (SD: 1.89) and 1.56 (SD: 1.87) (p=0.06), respectively. The means of mSCORE index in RA patients and in the control group were 2.84 (SD=2.86) and 1.56 (SD=1.87) (p=0.001), respectively. By using the SCORE risk index, 11% of RA patients were classified as of high risk, and with the use of mSCORE risk index, 36% were at high risk (p<0.001). CONCLUSION: The SCORE risk index is similar in both groups, but with the application of the mSCORE index, we recognized that RA patients have a higher 10-year risk of a fatal cardiovascular disease event, and this reinforces the importance of factors inherent to the disease not measured in the SCORE risk index, but considered in mSCORE risk index. PMID- 27267528 TI - Brazilian multicenter study of 71 patients with juvenile-onset Takayasu's arteritis: clinical and angiographic features. AB - OBJECTIVE: To describe the clinical and angiographic characteristics of Takayasu's arteritis in Brazilian children and adolescents. METHODS: A retrospective data collection was performed in 71 children and adolescents followed in 10 Brazilian reference centers in Pediatric Rheumatology. The evaluation was carried out in three different time points: from onset of symptoms to diagnosis, from the 6th to 12th month of diagnosis, and in the last visit. RESULTS: Of 71 selected patients, 51 (71.8%) were girls. The mean age of onset of symptoms and of time to diagnosis was 9.2 (+/-4.2) years and 1.2 (+/-1.4) years, respectively. At the end of the study, 20 patients were in a state of disease activity, 39 in remission and 5 had evolved to death. The most common symptoms in baseline assessment, second evaluation, and final evaluation were, respectively: constitutional, musculoskeletal, and neurological symptoms. A decrease in peripheral pulses was the most frequent cardiovascular signal, and an increase in erythrocyte sedimentation rate was the most frequent laboratory finding in all three evaluation periods. The tuberculin test was positive in 41% of those tested. Stenosis was the most frequent angiographic lesion, abdominal artery was the most affected segment, and angiographic type IV the most frequent. Most (90%) participants were treated with glucocorticoids, 85.9% required another immunosuppressive drug, and 29.6% underwent angioplasty. CONCLUSION: This is the largest study on juvenile-onset Takayasu arteritis, and a high number of patients under the age of 10 years, with predominance of constitutional symptoms early in the disease, was observed. PMID- 27267529 TI - Platelet-rich plasma for osteoarthritis treatment. AB - We conducted a comprehensive and systematic search of the literature on the use of platelet-rich plasma (PRP) in the treatment of osteoarthritis, using the Medline, Lilacs, Cochrane and SciELO databases, from May 2012 to October 2013. A total of 23 studies were selected, with nine being controlled trials and, of these, seven randomized, which included 725 patients. In this series, the group receiving PRP showed improvement in pain and joint function compared to placebo and hyaluronic acid. The response lasted up to two years and was better in milder cases. However it was found that there is no standardization in the PRP production method, neither in the number, timing, and volume of applications. Furthermore, the populations studied were not clearly described in many studies. Thus, these results should be analyzed with caution, and further studies with more standardized methods would be necessary for a more consistent conclusion about the PRP role in osteoarthritis. PMID- 27267530 TI - Periodontitis and systemic lupus erythematosus. AB - A large number of studies have shown a potential association between periodontal and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus (SLE). Similar mechanisms of tissue destruction concerning periodontitis and other autoimmune diseases have stimulated the study of a possible relationship between these conditions. This study aims to review the literature about this potential association and their different pathogenic mechanisms. Considering that periodontal disease is a disease characterized by inflammation influenced by infectious factors, such as SLE, it is plausible to suggest that SLE would influence periodontal disease and vice versa. However, this issue is not yet fully elucidated and several mechanisms have been proposed to explain this association, as deregulation mainly in innate immune system, with action of phagocytic cells and proinflammatory cytokines such as IL-1beta and IL 18 in both conditions' pathogenesis, leading to tissue destruction. However, studies assessing the relationship between these diseases are scarce, and more studies focused on common immunological mechanisms should be conducted to further understanding. PMID- 27267531 TI - Genetics of rheumatoid arthritis: a new boost is needed in Latin American populations. AB - Rheumatoid arthritis (RA) is an autoimmune inflammatory rheumatic disease which affects several organs and tissue, predominantly the synovial joints. Like many other autoimmune diseases, RA is a complex disease, where genetic variants, environmental factors and random events interact to trigger pathological pathways. Genetic implication in RA is evident, and recent advances have expanded our knowledge about the genetic factors that contribute to RA. An exponential increment in the number of genes associated with the disease has been described, mainly through gene wide screen studies (GWAS) involving international consortia with large patient cohorts. However, there are a few studies on Latin American populations. This article describes what is known about the RA genetics, the future that is emerging, and how this will develop a more personalized approach for the treatment of the disease. Latin American RA patients cannot be excluded from this final aim, and a higher collaboration with the international consortia may be needed for a better knowledge of the genetic profile of patients from this origin. PMID- 27267532 TI - Association between rheumatic fever and Takayasu's arteritis - Case report. AB - Takayasu's arteritis (TA) and rheumatic fever are diseases that can start with cardiac features, making the diagnosis difficult. There are reports of association of RF with Takayasu's arteritis beginning with cardiac involvement in pediatric patients. The aim of this study is to report the possible association of RF and TA in patients with cardiac abnormalities. We describe the case of an adolescent initially diagnosed with RF who progressed with changes that allowed making the diagnosis of TA. TA and RF are two important causes of valve involvement that may have systemic manifestations. PMID- 27267533 TI - Acute acalculous cholecystitis in systemic lupus erythematosus: a rare initial manifestation. AB - Acute acalculous cholecystitis is a very rare gastrointestinal manifestation in systemic lupus erythematosus and becomes rarer as an initial manifestation. There are only two cases reported. The authors report a 20-year-old black woman that presented acute acalculous cholecystitis revealed by abdominal computed tomography. During hospitalization, she was diagnosed systemic lupus erythematosus. Conservative treatment with antibiotics was performed with complete remission of the symptoms. Corticosteroid was started in ambulatory. Cholecystectomy has been the treatment of choice in acute acalculous cholecystitis as a complication of systemic lupus erythematosus. The patient responded well to conservative treatment, and surgery was not required. This case is unique in the way that corticosteroid was started in ambulatory care. We should not forget that the acute acalculous cholecystitis can be the initial presentation of systemic lupus erythematosus although its occurrence is very rare. Conservative treatment should be considered. Abdominal computed tomography was a determinant exam for better assessment of acute acalculous cholecystitis. PMID- 27267534 TI - Chronic polyarthritis as isolated manifestation of toxocariasis. AB - Human toxocariasis is a parasitic zoonosis mainly caused by Toxocara canis or Toxocara cati and is acquired by ingestion of the parasite's embryonated eggs. Arthralgia and/or arthritis were reported in up to 17% of the cases, generally with acute duration (less than 6 weeks). However, to our knowledge, chronic polyarthritis, as the isolated presentation of Toxocara infection, was not reported. One of the 5809 patients that was followed up at our service (0.017%) had chronic polyarthritis as the single manifestation of toxocariasis and was described herein. A 3-year-old girl was referred to our service with severe painful chronic polyarthritis for a period longer than 10 weeks and morning stiffness of 30min. Dog contact exposure history in the recreational areas of neighborhood was reported. Her exams showed high levels of eosinophils in peripheral blood (29%), bone marrow aspirate revealed marked eosinophilia (32%) and Toxocara enzyme-linked immunosorbent assay (Elisa) was positive (1:1280). She was treated with paracetamol (40mg/kg/day) and thiabendazole (25mg/kg/day) for 10 days, and all manifestations reduced. After eight months of follow-up, she was on clinical and laboratorial remission. In conclusion, we described a case of chronic polyarthritis, as isolated manifestation of toxocariasis, mimicking juvenile idiopathic arthritis and leukemia. Importantly, this zoonosis should be considered in patients with arthritis and eosinophilia. PMID- 27267535 TI - NCPDP recommendations for dose accumulation monitoring in the inpatient setting: Acetaminophen case model, version 1.0. AB - PURPOSE: Best practices and guidance are provided for improved electronic detection and alerting of inadvertent supratherapeutic cumulative doses of acetaminophen and other medications with narrow therapeutic ranges in inpatient settings. SUMMARY: Despite the use of medication safety technologies, overdosage and associated sentinel events continue to be serious problems in many inpatient settings. The tools needed to monitor and employ dose alerts, accumulators, and warning systems are available to reduce inadvertent overdose. Required are staff training and the implementation of processes that provide guidance and documentation of the drug reconciliation process from admittance to discharge for safe patient passage through the various transitions of care. Recommendations to achieve optimal patient safety outcomes include the adoption and integration of available technologies with full functionality configured to meet the institution's policies and processes, initial training and retraining of all staff who use these systems, continuing education of the patient care staff on the dosing safety requirements, and assigning a prominent role to the clinical pharmacist in the entire drug-use and reconciliation process. CONCLUSION: The key factors contributing to inadvertent overdosage in inpatient settings include a lack of recognition of recommended maximum daily dosages; failure to optimally communicate medication information at transitions of care; failure to optimally implement medication safety technologies, particularly dose accumulator calculation features and associated alerts; and alert fatigue and override. PMID- 27267536 TI - Preventing inpatient acetaminophen overexposure. PMID- 27267538 TI - Worldwide Exposures to Cardiovascular Risk Factors and Associated Health Effects: Current Knowledge and Data Gaps. AB - Information on exposure to, and health effects of, cardiovascular disease (CVD) risk factors is needed to develop effective strategies to prevent CVD events and deaths. Here, we provide an overview of the data and evidence on worldwide exposures to CVD risk factors and the associated health effects. Global comparative risk assessment studies have estimated that hundreds of thousands or millions of CVD deaths are attributable to established CVD risk factors (high blood pressure and serum cholesterol, smoking, and high blood glucose), high body mass index, harmful alcohol use, some dietary and environmental exposures, and physical inactivity. The established risk factors plus body mass index are collectively responsible for ~9.7 million annual CVD deaths, with high blood pressure accounting for more CVD deaths than any other risk factor. Age standardized CVD death rates attributable to established risk factors plus high body mass index are lowest in high-income countries, followed by Latin America and the Caribbean; they are highest in the region of central and eastern Europe and central Asia. However, estimates of the health effects of CVD risk factors are highly uncertain because there are insufficient population-based data on exposure to most CVD risk factors and because the magnitudes of their effects on CVDs in observational studies are likely to be biased. We identify directions for research and surveillance to better estimate the effects of CVD risk factors and policy options for reducing CVD burden by modifying preventable risk factors. PMID- 27267539 TI - The Importance of Bringing Science and Medicine to Lay Audiences. PMID- 27267540 TI - Letter by Providencia and Lambiase Regarding Article, "Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved Versus Reduced Ejection Fraction". PMID- 27267537 TI - Exercise Dose in Clinical Practice. AB - There is wide variability in the physical activity patterns of the patients in contemporary clinical cardiovascular practice. This review is designed to address the impact of exercise dose on key cardiovascular risk factors and on mortality. We begin by examining the body of literature that supports a dose-response relationship between exercise and cardiovascular disease risk factors, including plasma lipids, hypertension, diabetes mellitus, and obesity. We next explore the relationship between exercise dose and mortality by reviewing the relevant epidemiological literature underlying current physical activity guideline recommendations. We then expand this discussion to critically examine recent data pertaining to the impact of exercise dose at the lowest and highest ends of the spectrum. Finally, we provide a framework for how the key concepts of exercise dose can be integrated into clinical practice. PMID- 27267541 TI - Response to Letter Regarding Article, "Atrial Fibrillation Begets Heart Failure and Vice Versa: Temporal Associations and Differences in Preserved Versus Reduced Ejection Fraction". PMID- 27267542 TI - Palladium-Catalyzed ipso-Borylation of Aryl Sulfides with Diborons. AB - A catalytic Miyaura-type ipso-borylation of aryl sulfides with diboron reagents has been achieved, providing arylboronate esters of synthetic use. The key conditions to transform inherently reluctant C-S bonds into C-B bonds include a palladium-NHC (N-heterocyclic carbene) precatalyst, bis(pinacolato)diboron, and lithium hexamethyldisilazide. This protocol is applicable to a reasonable range of aryl alkyl sulfides. Twofold borylation was observed in the reaction of diphenyl sulfide. PMID- 27267543 TI - Hyper-recovery of platelets after induction therapy is a predictor of relapse free survival in acute myeloid leukemia. AB - We verified the association between standard clinical and laboratory variables and the risk of relapse in acute myeloid leukemia (AML), which led us to retrospectively examine the effect of regeneration of hematopoiesis in patients with newly diagnosed AML. We used data from 230 patients who obtained remission after cytarabine-based induction chemotherapy. Platelet counts >=500 * 109/L and hemoglobin levels >=9 g/dL on day 28 after treatment initiation were significantly associated with relapse-free survival (RFS) rate, conferring respective multivariate risk ratios of 0.38 (95% CI: 0.18-0.79) and 0.60 (95% CI: 0.40-0.89) for the occurrence of relapse or death. No disease relapse occurred in core binding factor leukemia patients whose platelet counts recovered >=500 * 109/L at 28 days after therapy initiation. We conclude that regeneration of hematopoiesis, especially platelet hyper-recovery, after induction chemotherapy is a significant predictor of RFS in patients with AML. PMID- 27267544 TI - Chemical Dimerizers in Three-Hybrid Systems for Small Molecule-Target Protein Profiling. AB - The identification of the molecular targets and mechanisms underpinning the beneficial or detrimental effects of small-molecule leads and drugs constitutes a crucial aspect of current drug discovery. Over the last two decades, three-hybrid (3H) systems have progressively taken an important position in the armamentarium of small molecule-target protein profiling technologies. Yet, a prerequisite for successful 3H analysis is the availability of appropriate chemical inducers of dimerization. Herein, we present a comprehensive and critical overview of the chemical dimerizers specifically applied in both yeast and mammalian three-hybrid systems for small molecule-target protein profiling within the broader scope of target deconvolution and drug discovery. Furthermore, examples and alternative suggestions for typical components of chemical dimerizers for 3H systems are discussed. As illustrated, more tools have become available that increase the sensitivity and efficiency of 3H-based screening platforms. Hence, it is anticipated that the great potential of 3H systems will further materialize in important contributions to drug discovery. PMID- 27267545 TI - Controlled Growth of Ultrathin Film of Organic Semiconductors by Balancing the Competitive Processes in Dip-Coating for Organic Transistors. AB - Ultrathin film with thickness below 15 nm of organic semiconductors provides excellent platform for some fundamental research and practical applications in the field of organic electronics. However, it is quite challenging to develop a general principle for the growth of uniform and continuous ultrathin film over large area. Dip-coating is a useful technique to prepare diverse structures of organic semiconductors, but the assembly of organic semiconductors in dip-coating is quite complicated, and there are no reports about the core rules for the growth of ultrathin film via dip-coating until now. In this work, we develop a general strategy for the growth of ultrathin film of organic semiconductor via dip-coating, which provides a relatively facile model to analyze the growth behavior. The balance between the three direct factors (nucleation rate, assembly rate, and recession rate) is the key to determine the growth of ultrathin film. Under the direction of this rule, ultrathin films of four organic semiconductors are obtained. The field-effect transistors constructed on the ultrathin film show good field-effect property. This work provides a general principle and systematic guideline to prepare ultrathin film of organic semiconductors via dip-coating, which would be highly meaningful for organic electronics as well as for the assembly of other materials via solution processes. PMID- 27267546 TI - Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion. AB - BACKGROUND: Renal ischemia-reperfusion injury, commonly caused by major operation and shock, leads to acute kidney injury and is associated with high morbidity and mortality. Cold-inducible ribonucleic acid-binding protein, a cold shock protein, has recently been identified as a damage-associated molecular pattern. We hypothesized that cold-inducible ribonucleic acid-binding protein exacerbates severity of injury in renal ischemia-reperfusion. METHODS: Renal ischemia was induced in an 8-week-old male C57BL/6 wild-type mice and Cirp(-/-) mice via bilateral clamping of renal pedicles for 30 minutes, followed by reperfusion for 5 or 24 hours and harvest of blood and renal tissue for analysis. Anti-cold inducible ribonucleic acid-binding protein antibody or non-immunized immunoglobulin G (IgG) was injected intravenously (10 mg/kg body weight) at time of reperfusion. RESULTS: After renal ischemia-reperfusion, Cirp(-/-) mice demonstrated a reduction of blood urea nitrogen and creatinine of 53% and 60%, respectively, compared with wild-type mice. Serum IL-6 levels were reduced significantly: 70% in Cirp(-/-) mice compared with wild-type mice after renal ischemia-reperfusion. Levels of nitrotyrosine, an oxidatively modified protein marker, and cyclooxygenase-2, an inflammatory mediator, also were significantly decreased in the kidneys of the Cirp(-/-) mice compared with wild-type mice after renal ischemia-reperfusion. Renal caspase-3 activity was decreased in Cirp(-/-) mice compared with wild-type mice after renal ischemia-reperfusion, which corresponded to the reduction of apoptotic cells determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Injection of neutralizing anti-cold-inducible ribonucleic acid-binding protein antibody into wild-type mice led to an 82% reduction in blood urea nitrogen compared with the vehicle after renal ischemia-reperfusion. CONCLUSION: Deficiency of cold inducible ribonucleic acid-binding protein results in less renal injury after renal ischemia-reperfusion by attenuating inflammation and oxidative stress. Furthermore, blockade of cold-inducible ribonucleic acid-binding protein shows a protective effect, indicating cold-inducible ribonucleic acid-binding protein as a target in the treatment of renal ischemia-reperfusion. PMID- 27267547 TI - Survival outcome of salvage hepatectomy in patients with local, recurrent hepatocellular carcinoma who underwent radiofrequency ablation as their first treatment. AB - BACKGROUND: Local recurrence is a specific problem after radiofrequency ablation of small hepatocellular carcinoma, and additional treatment is an important issue. We aimed to investigate the outcome of salvage hepatectomy in patients who develop local, recurrent hepatocellular carcinoma after treatment with radiofrequency ablation. METHODS: From 2001-2013, we reviewed 58 patients from 6 university hospitals with local, recurrent hepatocellular carcinoma who underwent salvage hepatectomy after their initial radiofrequency ablation treatment. Pathologic characteristics and prognostic factors influencing overall survival were analyzed. RESULTS: Noncurative resection, des-gamma carboxy prothrombin levels >40 mAU/mL, and multiple preceding treatments before salvage hepatectomy were negative prognostic factors for overall survival. The 5-year survivals for the prognostic factors were 0%, 24%, and 30%, respectively, after salvage hepatectomy, and 0%, 54%, and 54% after initial radiofrequency ablation treatment, respectively. As for the pathologic finding of local, recurrent hepatocellular carcinoma after radiofrequency ablation, vascular invasion was observed frequently in patients with increases in des-gamma carboxy prothrombin levels and with multiple preceding treatments before salvage hepatectomy with a frequency of 59% and 53%, respectively (P < .01 and .05). CONCLUSION: Noncurative resection, increases in serum des-gamma carboxy prothrombin, and multiple preceding treatments were prognostic factors for subsequent salvage hepatectomy; nevertheless, survival outcomes were still acceptable when a curative salvage hepatectomy was performed. Increases in serum des-gamma carboxy prothrombin and multiple preceding treatments were positive predictors for pathologic vascular invasion. These factors should be taken into consideration when selecting treatment modalities for locally recurrent hepatocellular carcinoma following radiofrequency ablation. Repetition of unsuccessful, loco-regional treatment would appear to decrease the potential survival. PMID- 27267548 TI - Impact of frailty on surgical outcomes: The right patient for the right procedure. AB - BACKGROUND: Measuring frailty may improve patient selection for high-risk procedures. METHODS: Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program for patients who underwent elective high-risk operative procedures, and a frailty index was used to classify the patients. RESULTS: Our study analyzed 232,352 patients with a mean age of 65 years; the majority of patients were males (54%) and white (78%). The most common procedure was colectomy (41%), followed by lower extremity bypass (25%), gastrectomy (8%), endovascular abdominal aneurism repair (7%), pancreatectomy (7%), cardiac operation (6%), nephrectomy (3%), and pulmonary resection (2%). A majority of the patients were classified as mildly frail (34%), followed by nonfrail (29%), moderately frail (21%), and severely frail (15%). On univariate analysis, age, race, procedure, sex, and frailty scores were associated with complications, prolonged duration of stay, and 30-day mortality (P < .0001). On multivariate analysis, frailty was associated with complications, prolonged duration of stay, and 30-day mortality. Increasing frailty disproportionately impacted mortality; colectomy showed the greatest mortality in severely frail patients (9.36%), followed by esophagectomy (8.2%), pulmonary resection (6.4%), pancreatectomy (5.8%), cardiac procedures (4.4%), gastrectomy (4.3%), nephrectomy (3.32%), endovascular abdominal aneurism repair (2.49%), and lower extremity bypass (2.41%; P = .0001). A similar association between duration of stay and morbidity with frailty was noted. CONCLUSION: Frailty has a significant impact on postoperative outcomes that varies with type of procedure. PMID- 27267549 TI - Is preoperative distinction between complicated and uncomplicated acute appendicitis feasible without imaging? AB - BACKGROUND: One of the main aims of appendicitis research is the differential diagnostics between complicated and uncomplicated acute appendicitis that enable provision of the optimal treatment for each patient. METHODS: Data in the present study were collected prospectively in our randomized antibiotic treatment for uncomplicated acute appendicitis trial (APPAC) comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (NCT01022567). We evaluated 705 patients who had acute appendicitis on computed tomography. Patients with uncomplicated acute appendicitis (n = 368) were compared with all complicated acute appendicitis patients (n = 337), and subgroup analyses were performed between uncomplicated acute appendicitis and an appendicolith appendicitis (CA1; n = 256) and uncomplicated acute appendicitis and perforation and/or abscess (CA2; n = 78). Age, sex, body temperature ( degrees C), duration of symptoms, white blood cell count (E9/L), and C-reactive protein (mg/L) were recorded on admission. Receiver operating characteristic curves were calculated for white blood cell count, C-reactive protein, and temperature. RESULTS: CA2 patients had significantly greater C-reactive protein levels (mean 122 and 47, respectively, P < .001) and longer duration of symptoms than uncomplicated acute appendicitis patients; 81% of CA2 patients and 38% of uncomplicated acute appendicitis patients had symptoms >24 hours before admission (P < .001). In receiver operating characteristic analysis, C-reactive protein and temperature had clinically significant results only in comparison with uncomplicated acute appendicitis and CA2 (area under the curve >0.7), but no optimum cutoff points could be identified. CONCLUSION: In clinical decision making, neither clinical findings nor laboratory markers are reliable enough to estimate the severity of the acute appendicitis accurately or to determine the presence of an appendicolith. The current results emphasize the role of computed tomography in the differential diagnosis of complicated and uncomplicated acute appendicitis. PMID- 27267550 TI - Natural history of nonenhancing lesions incidentally detected during the diagnosis of hepatocellular carcinoma. AB - BACKGROUND: Incidental detection of nonenhancing tumors during imaging studies for patients with classical hepatocellular carcinoma is not unusual. These tumors are considered to have a high potential of malignant transformation. The aim of this study was to clarify the natural history of such tumors. METHODS: In 93 patients who underwent liver resection for hepatocellular carcinoma, 138 nonenhancing or enhancing nodules without washout were detected during dynamic computed tomography and observed without further treatments. We subsequently compared the cumulative occurrence of new hepatocellular carcinomas to that of the malignant transformation of these lesions. We additionally compared the appearance of new hepatocellular carcinomas between the patients with (n = 93) and without (n = 782) nonenhancing lesions or enhancing lesions without washout. RESULTS: After a median follow-up period of 0.7 years (range, 0.2-6.8), the median intervals from resection to the appearance of new classical hepatocellular carcinoma and malignant transformation of nonenhancing lesions or enhancing lesions without washout were 1.6 years (95% confidence interval, 1.2-1.9) and 2.3 years (1.9-6.8 years; P = .002), respectively. On the other hand, the median intervals from resection to the appearance of new lesions in patients with and without nonenhancing lesions or enhancing lesions without washout were 1.6 years (95% confidence interval, 1.2-1.9) and 2.1 years (1.9-2.1 years; P = .031), respectively. CONCLUSION: During the natural history of nonenhancing lesions and enhancing lesions without washout that coexist with hepatocellular carcinoma, new lesions often develop prior to the malignant transformation of these lesions. This should be considered a risk factor for the appearance of new hepatocellular carcinoma. PMID- 27267551 TI - Long-term effects of physical exercise during rehabilitation in patients with severe burns. AB - BACKGROUND: We have reported that a 12-week exercise program is beneficial for the exercise performance of severely burned children. It is not known, however, whether the beneficial effects remain at 2 years postburn. METHODS: Severely burned children who received no long-term anabolic drugs were consented to this Institutional Review Board-approved study. Patients chose between a voluntary exercise program (EX-group) and no exercise (NoEX-group) after discharge from the acute burn unit. Peak torque per lean leg mass, maximal oxygen consumption, and percent predicted peak heart rate were assessed. In addition, body mass index percentile and lean body mass index were recorded. Both groups were compared for up to 2 years postburn using mixed multiple analysis of variance. RESULTS: A total of 125 patients with a mean age of 12 +/- 4 years were analyzed. Demographics between the EX-group (N = 82) and NoEX-group (N = 43) were comparable. In the EX-group, peak torque per lean leg mass, percent predicted peak heart rate, and maximal oxygen consumption increased significantly with exercise (P < .01). Between discharge and 12-24 months, body mass index percentile increased significantly in the EX-Group (P < .05) but did not change in the NoEX-group. There were no significant differences between groups in body mass index percentile, lean body mass index, peak torque per lean leg mass, and maximal oxygen consumption at 24 months postburn. CONCLUSION: Exercise significantly improves the physical performance of burned children. The benefits are limited to early time points, however, and greatly narrow with further recovery time. Continued participation in exercise activities or a maintenance exercise program is recommended for exercise-induced adaptations to continue. PMID- 27267552 TI - Survival outcomes after prolonged intensive care unit length of stay among trauma patients: The evidence for never giving up. AB - BACKGROUND: Prolonged intensive care unit length of stay (ICU-LOS) is associated with high mortality for medical and surgical patients. Existing literature suggests that this may not be true for trauma patients. The objective of this study was to determine mortality associated with varying ICU-LOS among trauma patients and to assess for independent predictors of mortality. METHODS: Adult ICU patients (16-64 years) in the National Trauma Data Bank (2007-2012) were categorized by ICU-LOS: 1, 2-9, 10-40, and >40 days (determined based on inflection points). Multivariable logistic regression was used to determine associations with mortality for each. Models accounted for clustering of patients within hospitals and potential confounding associated with: age, gender, race/ethnicity, insurance status, Injury Severity Score, blunt/penetrating injury, Glasgow Coma Scale, in-hospital complications, ventilator dependency, and emergency department disposition. RESULTS: Among the 596,598 patients included, 6.5% (n = 38,812) died. Mortality varied with ICU-LOS: 9.9%, 4.9%, 6.6%, and 9.8%. Age >35 years was a significant predictor of mortality in each. Injury Severity Score and the Glasgow Coma Scale independently predicted mortality in patients with LOS <=40 days as did penetrating injuries, cardiac arrest, and renal failure. Identification with non-Hispanic black race/ethnicity was also consistently significant. Once patients survived 9 days, mortality steadily decreased, remaining relatively stable until 40 days. Thereafter, trauma patients continued to demonstrate high survival with >87% remaining alive in the ICU >90 days. CONCLUSION: The results reveal that in contrast to expectations of high mortality associated with prolonged ICU-LOS, critically injured adult trauma patients who do not die within the first few days demonstrate an enhanced ability to survive, with an overall survival of >92% and maintained at >85% among extreme ICU-LOS (>40 days). The data advocate the utility of aggressive critical-care support for trauma patients, irrespective of duration of ICU stay. PMID- 27267553 TI - Living with an implantable cardioverter defibrillator: patients' preferences and needs for information provision and care options. AB - Aims: The clinical management and care of patients with an implantable cardioverter defibrillator (ICD) has shifted from face-to-face in-clinic visits to remote monitoring. Reduced interactions between patients and healthcare professionals may impede patients' transition to adapting post-implant. We examined patients' needs and preferences for information provision and care options and overall satisfaction with treatment. Methods and results: Patients implanted with a first-time ICD or defibrillator with cardiac resynchronization therapy (n = 389) within the last 2 years at Odense University Hospital were asked to complete a purpose-designed and standardized set of questionnaires. The level of satisfaction with information provision was high; only 13.1% were dissatisfied. Psychological support for patients (39.9%), their relatives (43.1%), and deactivation of the ICD towards end of life (47.8%) were among the top five topics that patients reported to have received no information about. The top five care options that patients had missed were talking to the same healthcare professional (75.2%), receiving ongoing feedback via remote monitoring (61.1%), having a personal conversation with a staff member 2-3 weeks post implant (59.6%), having an exercise tolerance test (52.5%), and staff asking how patients felt while hospitalized (50.4%). Patients with a secondary prevention indication and cardiac arrest survivors had specific needs, including a wish for a psychological consult post-discharge. Conclusion: Despite a high satisfaction level with information provision, particular topics are not broached with patients (e.g. device activation) and patients have unmet needs that are not met in current clinical practice. PMID- 27267554 TI - Results from a multicentre comparison of cryoballoon vs. radiofrequency ablation for paroxysmal atrial fibrillation: is cryoablation more reproducible? AB - AIM: Cryoballoon ablation (Cryoballoon) has emerged as a new alternative for the treatment of symptomatic drug-refractory atrial fibrillation (AF). Whether the results of Cryoballoon are more reproducible than those of radiofrequency (RF) ablation remains to be proved. METHODS AND RESULTS: A total of 860 consecutive patients undergoing a first ablation procedure for paroxysmal AF (467 treated with RF and 393 treated with Cryoballoon) were selected from a prospective multicentre survey of AF ablation (FrenchAF). Radiofrequency and Cryoballoon were compared regarding mid-term efficacy and safety. During a median follow-up of 14 months (interquartile range 8-23), patients treated with Cryoballoon displayed similar rates of freedom from atrial arrhythmia relapse in centres performing this technique (68-80% at 18 months). However, in centres performing RF, a greater heterogeneity in procedural results was observed (46-79% were free from atrial arrhythmia relapse at 18 months). On multivariate analysis, Cryoballoon (HR = 0.47, 95% CI 0.35-0.65, P < 0.001) and annual AF ablation caseload (HR = 0.87 per every 100 AF ablation procedures per year; 95% CI 0.80-0.96, P = 0.003) were independent predictors of procedural success. However, on sensitivity analysis, according to the ablation method, annual AF ablation caseload predicted only sinus rhythm maintenance in the subgroup of patients treated with RF. Analysis of interoperator results with Cryoballoon and RF confirmed lower reproducibility of RF, but suggested that besides caseload, other operator related factors may play a role. CONCLUSION: Cryoballoon seems to be less operator-dependent and more reproducible than RF in the setting of paroxysmal AF ablation. PMID- 27267555 TI - Dermal wound healing potency of single alkaloid (betaine) versus standardized crude alkaloid enriched-ointment of Evolvulus alsinoides. AB - CONTEXT: Evolvulus alsinoides Linn. (Convolvulaceae), well known as shankhpushpi in Ayurvedic text, is traditionally used for several healing purposes. OBJECTIVE: A comparative evaluation of dermal wound healing potential of acidic and basic alkaloid enriched-ointment (AAO and BAO) of aerial parts of E. alsinoides versus pure alkaloid, betaine (BEO), was undertaken. MATERIAL AND METHODS: The effect of topical application (50 mg/animal/day) of AAO-1%, AAO-2%, BAO-1%, BAO-2%, BEO 0.5% and BEO-1% was assessed through excision (14 days) and incision (10 days) models on rats. The percentage wound contraction, total protein content, and breaking strengths were determined followed by histopathological studies. RESULTS AND DISCUSSION: The total alkaloid in acidic and basic alkaloid enriched fractions was found to be 0.1114 and 0.1134 MUg/mL, respectively. Thus, 0.1528, 0.3056, 0.1380 and 0.2459 MUg of total alkaloid were estimated to be present in AAO-1%, AAO-2%, BAO-1% and BAO-2%, respectively. AAO and BAO promoted wound healing activity significantly in both the models. Higher rate of wound contraction (p < 0.001) with significant increase in protein content in the treatment groups (from 2.32 to 2.55) demonstrated stimulation of cellular proliferation and epithelization, which was further supported by histopathological reports. High skin breaking strength (mean value 393 in control was increased to the range of 535-572 in treated groups) proved a significant (p < 0.001) wound healing potential of E. alsinoides. Early dermal and epidermal regeneration in drug-treated groups also confirmed the positive effect. CONCLUSION: Observation of higher healing power of alkaloid enriched-ointment compared with single alkaloid ointment corroborated the synergy mechanism. PMID- 27267557 TI - The characteristics of emergency department presentations related to acute herbicide or insecticide poisoning in South Korea between 2011 and 2014. AB - The aim of this study was to examine epidemiologic data regarding acute herbicide or insecticide poisoning in adults from 2011 to 2014 at the national level in South Korea. Further, the association between governmental regulations involving pesticides and changes in pesticide poisoning occurrences over time was determined. Data were obtained from the emergency department (ED)-based Injury In depth Surveillance system conducted by the Korea Center for Disease Control and Prevention (KCDC). Governmental regulations on pesticides were downloaded from the homepage of the Korea Rural Development Administration. Pesticides were classified according to guidelines provided by the World Health Organization (WHO) and by the respective Resistance Action Committee (RAC). Trends in the number of ED presentations and case fatality rate (CFR) due to pesticide poisoning were investigated. The overall CFR due to poisoning from herbicides or insecticides in adults in South Korea was 16.8% during 2011-2014. However, CFR significantly decreased over the 4-year period. The ED presentations of paraquat (PQ) poisoning fell significantly, whereas poisoning due to glyphosate, glufosinate, or combined herbicides increased markedly over the 4 years. Between 2011 and 2013, PQ was the most common pesticide poisoning, whereas glyphosate became the most frequent in 2014. PQ produced the highest rate of fatality followed by endosulfan. Although the frequency of PQ poisoning decreased, which may be attributed to governmental regulations, the CFR and incidence of pesticide poisoning in adults remain a public health concern that needs to be addressed. PMID- 27267558 TI - Harvesting Broad Frequency Band Blue Energy by a Triboelectric-Electromagnetic Hybrid Nanogenerator. AB - Ocean wave associated energy is huge, but it has little use toward world energy. Although such blue energy is capable of meeting all of our energy needs, there is no effective way to harvest it due to its low frequency and irregular amplitude, which may restrict the application of traditional power generators. In this work, we report a hybrid nanogenerator that consists of a spiral-interdigitated electrode triboelectric nanogenerator (S-TENG) and a wrap-around electromagnetic generator (W-EMG) for harvesting ocean energy. In this design, the S-TENG can be fully isolated from the external environment through packaging and indirectly driven by the noncontact attractive forces between pairs of magnets, and W-EMG can be easily hybridized. Notably, the hybrid nanogenerator could generate electricity under either rotation mode or fluctuation mode to collect energy in ocean tide, current, and wave energy due to the unique structural design. In addition, the characteristics and advantages of outputs indicate that the S-TENG is irreplaceable for harvesting low rotation speeds (<100 rpm) or motion frequencies (<2 Hz) energy, which fits the frequency range for most of the water wave based blue energy, while W-EMG is able to produce larger output at high frequencies (>10 Hz). The complementary output can be maximized and hybridized for harvesting energy in a broad frequency range. Finally, a single hybrid nanogenerator unit was demonstrated to harvest blue energy as a practical power source to drive several LEDs under different simulated water wave conditions. We also proposed a blue energy harvesting system floating on the ocean surface that could simultaneously harvest wind, solar, and wave energy. The proposed hybrid nanogenerator renders an effective and sustainable progress in practical applications of the hybrid nanogenerator toward harvesting water wave energy offered by nature. PMID- 27267559 TI - The successful use of familial searching in six Hungarian high profile cases by applying a new module in Familias 3. AB - Commonly DNA profiles obtained from biological samples found at crime scenes or of unknown bodies are searched against a large national or local database of reference and crime scene DNA profiles. The aim is to find a direct match, i.e. an identical profile or in the case of a mixture, at least an overlap of all alleles. Familial searching is, instead, the concept of searching for relatives of a stain donor in the database, i.e. a quest for relatives of the possible perpetrator or an unidentified body. The current paper provides the tool to perform effective searches for relatives of a target DNA profile in a large database. In addition, the algorithm accounts for mixtures which is common in crime stains. Specifically we focus on six high profile Hungarian cases where familial searching has succeeded in providing investigative leads. An implementation of the methods is included in the latest version of the software Familias, freely available at www.familias.no. PMID- 27267556 TI - Advances and Future Directions for Tuberous Sclerosis Complex Research: Recommendations From the 2015 Strategic Planning Conference. AB - On March 10 to March 12, 2015, the National Institute of Neurological Disorders and Stroke and the Tuberous Sclerosis Alliance sponsored a workshop in Bethesda, Maryland, to assess progress and new opportunities for research in tuberous sclerosis complex with the goal of updating the 2003 Research Plan for Tuberous Sclerosis (http://www.ninds.nih.gov/about_ninds/plans/tscler_research_plan.htm). In addition to the National Institute of Neurological Disorders and Stroke and Tuberous Sclerosis Alliance, participants in the strategic planning effort and workshop included representatives from six other Institutes of the National Institutes of Health, the Department of Defense Tuberous Sclerosis Complex Research Program, and a broad cross-section of basic scientists and clinicians with expertise in tuberous sclerosis complex along with representatives from the pharmaceutical industry. Here we summarize the outcomes from the extensive premeeting deliberations and final workshop recommendations, including (1) progress in the field since publication of the initial 2003 research plan for tuberous sclerosis complex, (2) the key gaps, needs, and challenges that hinder progress in tuberous sclerosis complex research, and (3) a new set of research priorities along with specific recommendations for addressing the major challenges in each priority area. The new research plan is organized around both short-term and long-term goals with the expectation that progress toward specific objectives can be achieved within a five to ten year time frame. PMID- 27267560 TI - A quantitative headspace-solid-phase microextraction-gas chromatography-flame ionization detector method to analyze short chain free fatty acids in rat feces. AB - This study sought to develop and validate a quantitative method to analyze short chain free fatty acids (SCFAs) in rat feces by solid-phase microextraction and gas chromatography (SPME-GC) using the salt mixture ammonium sulfate and sodium dihydrogen phosphate as salting out agent. Conditioning and extraction time, linearity, limits of detection and quantification, repeatability, and recovery were evaluated. The proposed method allows quantification with improved sensitivity as compared with other methods exploiting SPME-GC. The method has been applied to analyze rat fecal samples, quantifying acetic, propionic, isobutyric, butyric, isopentanoic, pentanoic, and hexanoic acids. PMID- 27267561 TI - The Pareto Analysis for Establishing Content Criteria in Surgical Training. AB - INTRODUCTION: Current surgical training is still highly dependent on expensive operating room (OR) experience. Although there have been many attempts to transfer more training to the skills laboratory, little research is focused on which technical behaviors can lead to the highest profit when they are trained outside the OR. The Pareto principle states that in any population that contributes to a common effect, a few account for the bulk of the effect. This principle has been widely used in business management to increase company profits. This study uses the Pareto principle for establishing content criteria for more efficient surgical training. METHOD: A retrospective study was conducted to assess verbal guidance provided by 9 supervising surgeons to 12 trainees performing 64 laparoscopic cholecystectomies in the OR. The verbal corrections were documented, tallied, and clustered according to the aimed change in novice behavior. The corrections were rank ordered, and a cumulative distribution curve was used to calculate which corrections accounted for 80% of the total number of verbal corrections. RESULTS: In total, 253 different verbal corrections were uttered 1587 times and were categorized into 40 different clusters of aimed changes in novice behaviors. The 35 highest-ranking verbal corrections (14%) and the 11 highest-ranking clusters (28%) accounted for 80% of the total number of given verbal corrections. CONCLUSIONS: Following the Pareto principle, we were able to identify the aspects of trainee behavior that account for most corrections given by supervisors during a laparoscopic cholecystectomy on humans. This strategy can be used for the development of new training programs to prepare the trainee in advance for the challenges encountered in the clinical setting in an OR. PMID- 27267562 TI - Reliability and Validity of 3 Methods of Assessing Orthopedic Resident Skill in Shoulder Surgery. AB - OBJECTIVE: Traditional measures for evaluating resident surgical technical skills (e.g., case logs) assess operative volume but not level of surgical proficiency. Our goal was to compare the reliability and validity of 3 tools for measuring surgical skill among orthopedic residents when performing 3 open surgical approaches to the shoulder. METHODS: A total of 23 residents at different stages of their surgical training were tested for technical skill pertaining to 3 shoulder surgical approaches using the following measures: Objective Structured Assessment of Technical Skills (OSATS) checklists, the Global Rating Scale (GRS), and a final pass/fail assessment determined by 3 upper extremity surgeons. Adverse events were recorded. The Cronbach alpha coefficient was used to assess reliability of the OSATS checklists and GRS scores. Interrater reliability was calculated with intraclass correlation coefficients. Correlations among OSATS checklist scores, GRS scores, and pass/fail assessment were calculated with Spearman rho. Validity of OSATS checklists was determined using analysis of variance with postgraduate year (PGY) as a between-subjects factor. Significance was set at p < 0.05 for all tests. RESULTS: Criterion validity was shown between the OSATS checklists and GRS for the 3 open shoulder approaches. Checklist scores showed superior interrater reliability compared with GRS and subjective pass/fail measurements. GRS scores were positively correlated across training years. The incidence of adverse events was significantly higher among PGY-1 and PGY-2 residents compared with more experienced residents. CONCLUSION: OSATS checklists are a valid and reliable assessment of technical skills across 3 surgical shoulder approaches. However, checklist scores do not measure quality of technique. Documenting adverse events is necessary to assess quality of technique and ultimate pass/fail status. Multiple methods of assessing surgical skill should be considered when evaluating orthopedic resident surgical performance. PMID- 27267563 TI - Objective Assessment of Laparoscopic Force and Psychomotor Skills in a Novel Virtual Reality-Based Haptic Simulator. AB - BACKGROUND: Most of the commercially available virtual reality-based laparoscopic simulators do not effectively evaluate combined psychomotor and force-based laparoscopic skills. Consequently, the lack of training on these critical skills leads to intraoperative errors. OBJECTIVES: To assess the effectiveness of the novel virtual reality-based simulator, this study analyzed the combined psychomotor (i.e., motion or movement) and force skills of residents and expert surgeons. The study also examined the effectiveness of real-time visual force feedback and tool motion during training. DESIGN: Bimanual fundamental (i.e., probing, pulling, sweeping, grasping, and twisting) and complex tasks (i.e., tissue dissection) were evaluated. In both tasks, visual feedback on applied force and tool motion were provided. The skills of the participants while performing the early tasks were assessed with and without visual feedback. Participants performed 5 repetitions of fundamental and complex tasks. Reaction force and instrument acceleration were used as metrics. SETTING: Surgical Gastroenterology, Government Stanley Medical College and Hospital; Institute of Surgical Gastroenterology, Madras Medical College and Rajiv Gandhi Government General Hospital. PARTICIPANTS: Residents (N = 25; postgraduates and surgeons with <2 years of laparoscopic surgery) and expert surgeons (N = 25; surgeons with >4 and <=10 years of laparoscopic surgery). RESULTS: Residents applied large forces compared with expert surgeons and performed abrupt tool movements (p < 0.001). However, visual + haptic feedback improved the performance of residents (p < 0.001). In complex tasks, visual + haptic feedback did not influence the applied force of expert surgeons, but influenced their tool motion (p < 0.001). Furthermore, in complex tissue sweeping task, expert surgeons applied more force, but were within the tissue damage limits. In both groups, exertion of large forces and abrupt tool motion were observed during grasping, probing or pulling, and tissue sweeping maneuvers (p < 0.001). CONCLUSIONS: Modern day curriculum based training should evaluate the skills of residents with robust force and psychomotor-based exercises for proficient laparoscopy. Visual feedback on force and motion during training has the potential to enhance the learning curve of residents. PMID- 27267564 TI - Proteome changes in rat serum after a chronic ingestion of enriched uranium: Toward a biological signature of internal contamination and radiological effect. AB - The civilian and military use of uranium results in an increased risk of human exposure. The toxicity of uranium results from both its chemical and radiological properties that vary with isotopic composition. Validated biomarkers of health effects associated with exposure to uranium are neither sensitive nor specific to uranium radiotoxicity and/or radiological effect. This study aimed at investigating if serum proteins could be useful as biomarkers of both uranium exposure and radiological effect. Male Sprague-Dawley rats were chronically exposed through drinking water to low levels (40mg/L, corresponding to 1mg of uranium per animal per day) of either 4% (235)U-enriched uranium (EU) or 12% EU during 6 weeks. A proteomics approach based on two-dimensional electrophoresis (2D-DIGE) and mass spectrometry (MS) was used to establish protein expression profiles that could be relevant for discriminating between groups, and to identify some differentially expressed proteins following uranium ingestion. It demonstrated that the expressions of 174 protein spots over 1045 quantified spots were altered after uranium exposure (p<0.05). Using both inferential and non supervised multivariate statistics, we show sets of spots features that lead to a clear discrimination between controls and EU exposed groups on the one hand (21 spots), and between 4% EU and 12% EU on the other hand (7 spots), showing that investigation of the serum proteome may possibly be of relevance to address both uranium contamination and radiological effect. Finally, using bioinformatics tools, pathway analyses of differentially expressed MS-identified proteins find that acute phase, inflammatory and immune responses as well as oxidative stress are likely involved in the response to contamination, suggesting a physiological perturbation, but that does not necessarily lead to a toxic effect. PMID- 27267566 TI - Sequenom, the U.S. Supreme Court, and Personalized Medicine. PMID- 27267565 TI - Microfluidics in systems biology-hype or truly useful? AB - Systems biology often relies on large-scale measurements and model-building to understand how complex biological systems function. Microfluidic technology has been touted as a tool for high-throughput experiments and has been a valuable tool to some systems biology research. This review focuses on applications where microfluidics can enhance experimental sensitivity and throughput, particularly in recent development in single-cell analyses and analyses on multi-cellular or complex biological entities. We conclude that microfluidics is not necessarily always useful for systems biology, but when used appropriately can greatly enhance experimentalists' ability to measure and control, and thereby enhance the understanding of and expand the utility of biological systems. PMID- 27267567 TI - On the intracellular release mechanism of hydrophobic cargo and its relation to the biodegradation behavior of mesoporous silica nanocarriers. AB - The intracellular release mechanism of hydrophobic molecules from surface functionalized mesoporous silica nanoparticles was studied in relation to the biodegradation behavior of the nanocarrier, with the purpose of determining the dominant release mechanism for the studied drug delivery system. To be able to follow the real-time intracellular release, a hydrophobic fluorescent dye was used as model drug molecule. The in vitro release of the dye was investigated under varying conditions in terms of pH, polarity, protein and lipid content, presence of hydrophobic structures and ultimately, in live cancer cells. Results of investigating the drug delivery system show that the degradation and drug release mechanisms display a clear interdependency in simple aqueous solvents. In pure aqueous media, the cargo release was primarily dependent on the degradation of the nanocarrier, while in complex media, mimicking intracellular conditions, the physicochemical properties of the cargo molecule itself and its interaction with the carrier and/or surrounding media were found to be the main release governing factors. Since the material degradation was retarded upon loading with hydrophobic guest molecules, the cargo could be efficiently delivered into live cancer cells and released intracellularly without pronounced premature release under extracellular conditions. From a rational design point of view, pinpointing the interdependency between these two processes can be of paramount importance considering future applications and fundamental understanding of the drug delivery system. PMID- 27267568 TI - Predictive models reduce talent development costs in female gymnastics. AB - This retrospective study focuses on the comparison of different predictive models based on the results of a talent identification test battery for female gymnasts. We studied to what extent these models have the potential to optimise selection procedures, and at the same time reduce talent development costs in female artistic gymnastics. The dropout rate of 243 female elite gymnasts was investigated, 5 years past talent selection, using linear (discriminant analysis) and non-linear predictive models (Kohonen feature maps and multilayer perceptron). The coaches classified 51.9% of the participants correct. Discriminant analysis improved the correct classification to 71.6% while the non linear technique of Kohonen feature maps reached 73.7% correctness. Application of the multilayer perceptron even classified 79.8% of the gymnasts correctly. The combination of different predictive models for talent selection can avoid deselection of high-potential female gymnasts. The selection procedure based upon the different statistical analyses results in decrease of 33.3% of cost because the pool of selected athletes can be reduced to 92 instead of 138 gymnasts (as selected by the coaches). Reduction of the costs allows the limited resources to be fully invested in the high-potential athletes. PMID- 27267569 TI - Corrigendum to "Differential Arc expression in the hippocampus and striatum during the transition from attentive to automatic navigation on a plus maze" [Neurobiol. Learn. Mem. 131 (2016) 36-45]. PMID- 27267570 TI - Doxorubicin-loaded fucoidan capped gold nanoparticles for drug delivery and photoacoustic imaging. AB - Polymer nanoparticles are emerging as a useful tool for a wide variety of biomedical and therapeutic applications. The present study demonstrates the multifunctional doxorubicin-loaded fucoidan capped gold nanoparticles (DOX-Fu AuNPs) for drug delivery and photoacoustic imaging (PAI). Biocompatible AuNPs were synthesized using a naturally occurring fucoidan (Fu) as a capping and reducing agent. The Fu AuNPs synthesis was determined using UV-visible spectrum, and it was further characterized using high resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis. The release of DOX from DOX-Fu AuNPs was greater in acidic pH (4.5) than in neutral pH (7.4). The in vitro cytotoxic effect of fucoidan, Fu AuNPs, DOX, and DOX-Fu AuNPs inhibited the proliferation of human breast cancer cells with an inhibitory concentration of 35MUg/mL, 30MUg/mL, 15MUg/mL, and 5MUg/mL at 24h. DOX-Fu AuNPs induced both early and late apoptosis in a concentration-dependent manner compared with untreated control cells. The ability of DOX-Fu AuNPs as a contrast agent for in vitro breast cancer imaging with PAI has been evaluated. These results suggest that the multifunctional DOX-Fu AuNPs for drug delivery and PAI can soon provide considerable contribution to human health. PMID- 27267571 TI - Preparation and sustainable release of modified konjac glucomannan/chitosan nanospheres. AB - Biodegradable and biocompatible polymer nanospheres are useful materials for controlled drug delivery. In the present study, novel composite nanospheres were prepared from carboxymethyl konjac glucomannan (CKGM) and 2-hydroxypropyl trimethyl ammonium chloride chitosan (HACC) as a vaccine delivery vehicle by electrostatic complexation in a neutral aqueous solution without the use of chemical crosslinkers. By altering the CKGM and HACC concentrations, the average CKGM/HACC particle size could be tuned from approximately 600nm to 1460nm and the zeta potential from 39mV to 50mV. Furthermore, using ovalbumin (OVA) as a model molecule for vaccines, various parameters were determined to affect the CKGM/HACC nanosphere encapsulation efficiency and in vitro controlled release properties. Under optimum conditions, the OVA encapsulation efficiency of CKGM/HACC nanospheres was 71.8%, while sustained and continuous in vitro OVA release over a period of more than 24h was observed. Therefore, CKGM/HACC nanospheres are novel drug delivery carriers with great potential for medical applications. PMID- 27267572 TI - Optimization of chitin yield from shrimp shell waste by Bacillus subtilis and impact of gamma irradiation on production of low molecular weight chitosan. AB - Chitin and chitosan have been produced from the exoskeletons of crustacean shells such as shrimps. In this study, seventy bacterial isolates, isolated from soil, were tested for proteolytic enzymes production. The most efficient one, identified as Bacillus subtilis, was employed to extract chitin from shrimp shell waste (SSW). Following one-variable-at-a-time approach, the relevant factors affecting deproteinization (DP) and demineralization (DM) were sucrose concentration (10%, w/v), SSW concentration (5%, w/v), inoculum size (15%, v/v), and fermentation time (6days). These factors were optimized subsequently using Box-Behnken design and response surface methodology. Maximum DP (97.65%) and DM (82.94%) were predicted at sucrose concentration (5%), SSW concentration (12.5%), inoculum size (10%, containing 35*10(8) CFU/mL), and fermentation time (7days). The predicted optimum values were verified by additional experiment. The values of DP (96.0%) and DM (82.1%) obtained experimentally correlated to the predicted values which justify the authenticity of optimum points. Overall 1.3-fold increase in DP% and DM% was obtained compared with 75.27% and 63.50%, respectively, before optimization. Gamma-irradiation (35kGy) reduced deacetylation time of irradiated chitin by 4.5-fold compared with non-irradiated chitin. The molecular weight of chitosan was decreased from 1.9*10(6) (non irradiated) to 3.7*10(4)g/mol (at 35kGy). PMID- 27267573 TI - Synthesis of water soluble chitosan derivatives with halogeno-1,2,3-triazole and their antifungal activity. AB - Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed prior to further utilization. Three novel water soluble chitosan derivatives containing 1,2,3- triazole with or without halogen was designed and synthesized. Their antifungal activity against three kinds of phytopathogens was estimated by hyphal measurement in vitro. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that thiazolyl groups enable the synthesized chitosan to possess obviously better antifungal activity. Moreover, CTCTS and BTCTS, which have halogens at the periphery of polymers, inhibited the growth of tested phytopathogens more effectively with inhibitory indices of 81-93% at 1.0mg/mL. The halogens could have a synergistic effect with triazole as they exhibited antifungal activity and electron-withdrawing capacity, which improve the antifungal activity of chitosan derivatives. PMID- 27267574 TI - Fabrication of electrospun almond gum/PVA nanofibers as a thermostable delivery system for vanillin. AB - In this study, the fabrication of vanillin incorporated almond gum/polyvinyl alcohol (PVA) nanofibers through electrospinning has been investigated. Electrospinning of only almond gum was proved impossible. It was found that the aqueous solution of almond gum/PVA (80:20, concentration=7% (w/w)) containing 3% (w/w) vanillin could have successfully electrospun to uniform nanofibers with diameters as low as 77nm. According to the thermal analysis, incorporated vanillin in almond gum/PVA nanofibers showed higher thermal stability than free vanillin, making this composite especially suitable for high temperature applications. XRD and FTIR analyses proved the presence of vanillin in the almond gum/PVA nanofibers. It was also found that vanillin was dispersed as big crystallites in the matrix of almond gum/PVA nanofibers. FTIR analysis showed almond gum and PVA had chemical cross-linking by etheric bonds between COH groups of almond gum and OH groups of PVA. Also, in the nanofibers, there were no major interaction between vanillin and either almond gum or PVA. PMID- 27267575 TI - 3D Printed scaffolds with bactericidal activity aimed for bone tissue regeneration. AB - Nowadays, the incidence of bone disorders has steeply ascended and it is expected to double in the next decade, especially due to the ageing of the worldwide population. Bone defects and fractures lead to reduced patient's quality of life. Autografts, allografts and xenografts have been used to overcome different types of bone injuries, although limited availability, immune rejection or implant failure demand the development of new bone replacements. Moreover, the bacterial colonization of bone substitutes is the main cause of implant rejection. To vanquish these drawbacks, researchers from tissue engineering area are currently using computer-aided design models or medical data to produce 3D scaffolds by Rapid Prototyping (RP). Herein, Tricalcium phosphate (TCP)/Sodium Alginate (SA) scaffolds were produced using RP and subsequently functionalized with silver nanoparticles (AgNPs) through two different incorporation methods. The obtained results revealed that the composite scaffolds produced by direct incorporation of AgNPs are the most suitable for being used in bone tissue regeneration since they present appropriate mechanical properties, biocompatibility and bactericidal activity. PMID- 27267576 TI - A Summary of the First HIV Microbiome Workshop 2015. AB - The role of microbiota in the pathogenesis of HIV infection has become the subject of intense research in recent years. A rapidly growing amount of data suggest that microbial dysbiosis-in the gut or the genital tract-can influence HIV transmission and/or disease progression; however, a deeper understanding of the mechanisms involved is lacking. To better understand the relationship between the microbiome and HIV infection, investigators from a wide variety of disciplines, including those working in basic and clinical HIV studies, cardiovascular disease, reproductive health, and bioinformatics, gathered at the first International Workshop on Microbiome in HIV Pathogenesis, Prevention and Treatment, at NIH on 7 and 8 April, 2015. PMID- 27267577 TI - Saksenaea erythrospora infection after medical tourism for esthetic breast augmentation surgery. AB - BACKGROUND: Mucormycosis caused by Saksenaea erythrospora is rarely reported in humans. Three previous cases have been reported in the literature, two associated with trauma (a sailing accident in Argentina and a combat trauma in Iraq) and one as a cause of invasive rhinosinusitis (India), all in immunocompetent patients . The first case of mucormycosis following esthetic surgery, associated with medical tourism, is reported herein. CASE REPORT: A case study of an S. erythrospora infection in an immunocompetent woman after the completion of esthetic surgery (dermolipectomy and breast augmentation) is reported. The infection presented as a rapidly progressive necrotizing infection of the skin and soft tissue, which required a bilateral mastectomy and extensive surgical debridement associated with prolonged antifungal therapy. The organism was identified phenotypically and confirmed biologically after rDNA amplification and sequencing. Two months later, the patient remains hospitalized awaiting the start of reconstructive surgeries. The present case is, to the best of the authors' knowledge, the first report from Colombia. CONCLUSIONS: Mucormycosis should be considered in the differential diagnosis of necrotizing infections of the skin and soft tissue that evolve rapidly after cosmetic surgery performed in tropical or subtropical countries. PMID- 27267578 TI - A man with disabling low back pain: Echinococcus of the sacrum. AB - Bone involvement in hydatid disease is rare, and when it does occur, the most common sites of involvement are the spine and pelvis. A case of bone hydatid disease involving the sacrum is reported here. PMID- 27267580 TI - Comparative Transcriptome Analysis of Two Ipomoea aquatica Forsk. Cultivars Targeted To Explore Possible Mechanism of Genotype-Dependent Accumulation of Cadmium. AB - A low-shoot-Cd (QLQ) and a high-shoot-Cd cultivar (T308) of water spinach (Ipomoea aquatica Forsk.) were used to investigate molecular mechanism of the genotype difference in cadmium (Cd) accumulation. RNA-Seq under 9 and 72 h cadmium exposures (5 mg L(-1)) were undertaken to explore Cd induced genotype differences in molecular processes. In total, 253 747 540 clean reads were assembled into 57 524 unigenes. Among them, 6136 and 10 064 unigenes were differentially expressed in QLQ and T308, respectively. Cell wall biosynthesis genes, such as GAUT and laccase, and three Cd efflux genes (Nramp5, MATE9, and YSL7) had higher expression levels in QLQ, while the genes in sulfur and glutathione metabolism pathway, e.g., sulfate transporter and cysteine synthase, showed higher expression levels in T308. These findings would be useful for further understanding of the mechanisms related to genotype-dependent Cd accumulation and developing the molecular assisted screening and breeding of low shoot-Cd cultivars for water spinach. PMID- 27267579 TI - Chromosome fusions triggered by noncoding RNA. AB - Chromosomal fusions are common in normal and cancer cells and can produce aberrant gene products that promote transformation. The mechanisms driving these fusions are poorly understood, but recurrent fusions are widespread. This suggests an underlying mechanism, and some authors have proposed a possible role for RNA in this process. The unicellular eukaryote Oxytricha trifallax displays an exorbitant capacity for natural genome editing, when it rewrites its germline genome to form a somatic epigenome. This developmental process provides a powerful model system to directly test the influence of small noncoding RNAs on chromosome fusion events during somatic differentiation. Here we show that small RNAs are capable of inducing chromosome fusions in 4 distinct cases (out of 4 tested), including one fusion of 3 chromosomes. We further show that these RNA mediated chromosome fusions are heritable over multiple sexual generations and that transmission of the acquired fusion is associated with endogenous production of novel piRNA molecules that target the fused junction. We also demonstrate the capacity of a long noncoding RNA (lncRNA) to induce chromosome fusion of 2 distal germline loci. These results underscore the ability of short-lived, aberrant RNAs to act as drivers of chromosome fusion events that can be stably transmitted to future generations. PMID- 27267582 TI - Synthesis and Coordination Chemistry of a Phosphine-Decorated Fluorescein: "Double Turn-On" Sensing of Gold(III) Ions in Water. AB - Although phosphine ligands are ubiquitous in transition metal chemistry, few reports of fluorescent phosphines exist that explore the effect of metal coordination on the photophysical properties of a phosphine-bound fluorescent group. The coordination chemistry of a derivative of fluorescein decorated with an o-phenylene-linked phosphine group has been studied with late transition metals. An Au(I) complex of the phosphine-decorated fluorescein has been structurally characterized, showing that the metal center is held closely over the plane of the fluorophore. Despite the presence of the heavy metal center, however, the phosphine-gold complex displays greatly increased fluorescence compared to the free ligand, in which photoelectron transfer from the lone-pair bearing phosphine causes low emission. The phosphine-decorated fluorescein ligand was tested in a simple sensing system for metal ions in aqueous solution and shows a "turn-on" response to Au, Ag, and Hg, with an especially dramatic response to Au(III) species. The selectivity for Au(III) was determined to be the result of a "double turn-on" response that is both reaction- and coordination based. PMID- 27267581 TI - High rates of venous thromboembolic events in patients undergoing systemic therapy for urothelial carcinoma: A systematic review and meta-analysis. AB - BACKGROUND: Patients undergoing systemic therapy for urothelial carcinoma (UC) are at increased risk for venous thromboembolic (VTE) events. The objective of the current study was to determine the rate of VTE events in patients undergoing systemic therapy for UC and assess factors affecting this rate. METHODS: This study was registered with the PROSPERO database (CRD42015025774). We searched Pubmed, MEDLINE, EMBASE, The Cochrane Library, CINAHL, and Web of Science libraries through August 2014. As per PRISMA guidelines, 2 reviewers independently reviewed titles and abstracts. Disagreements were arbitrated by a third reviewer. After full text review, data were abstracted and pooled using a random effects model. Authors were contacted for clarification of data. To determine VTE risk factors, subgroup analyses and meta-regression were conducted. RESULTS: We identified 3,635 publications in the initial search, of which 410 met inclusion criteria for full text review. Of these, we were able to obtain data on the outcome of interest for 62 publications. A total of 5,082 patients, of which 77% were male, underwent systemic therapy for UC, with 373 VTE events. The proportion of patients who had had prior surgery, chemotherapy, or radiation was 55%, 25%, and 9%, respectively. Fixed effects and random effects models were used to estimate the VTE rate, yielding event rates of 6.7% and 5.4%, respectively. CONCLUSIONS: VTE occurs frequently in patients undergoing systemic therapy for UC. The VTE rate was affected by the country of origin, history of radiation, as well as by the systemic treatment class. The study was limited by the incomplete reporting of all variables of interest. PMID- 27267583 TI - The role of the carrier in the formulation of pharmaceutical solid dispersions. Part II: amorphous carriers. AB - INTRODUCTION: Amorphous solid dispersions are considered as one of the most powerful strategies to formulate poorly soluble drugs. They are made up of an active pharmaceutical ingredient (API) dispersed at the molecular level in an amorphous polymeric carrier. As the latter component constitutes the largest part of the formulation, its characteristics will contribute to a large extent to the properties and behavior of the solid dispersion. Areas covered: Amorphous polymers are most often used in modern solid dispersion formulations. This review discusses carrier properties like molecular weight, conformation, hygroscopicity, their stabilization effects, issues related to solid dispersion manufacturing technology, response to downstream processing, and potential to generate supersaturation, next to criteria to select a carrier to formulate stable amorphous solid dispersions. Expert opinion: Different amorphous carriers lead to solid dispersions with various properties in terms of physical stability, phase behavior and drug release rate and extent. Despite more than 50 years of intensive research in this field it remains difficult to predict what carrier is best suited for a given API, pointing to the complex nature of this formulation strategy. Sustained efforts to understand the link and complex interplay between material properties, processing parameters, physical stability and dissolution behavior are required from pharmaceutical scientists with a strong physicochemical background to shift the development from trial and error to science driven. PMID- 27267584 TI - Probing the pigment binding sites in LHCII with resonance Raman spectroscopy: The effect of mutations at S123. AB - Resonance Raman spectroscopy was used to evaluate the structure of light harvesting chlorophyll (Chl) a/b complexes of photosystem II (LHCII), reconstituted from wild-type (WT) and mutant apoproteins over-expressed in Escherichia coli. The point mutations involved residue S123, exchanged for either P (S123P) or G (S123G). In all reconstituted proteins, lutein 2 displayed a distorted conformation, as it does in purified LHCII trimers. Reconstituted WT and S123G also exhibited a conformation of bound neoxanthin (Nx) molecules identical to the native protein, while the S123P mutation was found to induce a change in Nx conformation. This structural change of neoxanthin is accompanied by a blue shift of the absorption of this carotenoid molecule. The interactions assumed by (and thus the structure of the binding sites of) the bound Chls b were found identical in all the reconstituted proteins, and only marginally perturbed as compared to purified LHCII. The interactions assumed by bound Chls a were also identical in purified LHCII and the reconstituted WT. However, the keto carbonyl group of one Chl a, originally free-from-interactions in WT LHCII, becomes involved in a strong H-bond with its environment in LHCII reconstituted from the S123P apoprotein. As the absorption in the Qy region of this protein is identical to that of the LHCII reconstituted from the WT apoprotein, we conclude that the interaction state of the keto carbonyl of Chl a does not play a significant role in tuning the binding site energy of these molecules. PMID- 27267585 TI - Insights into Stereoselective Aminomethylation Reaction of alpha,beta-Unsaturated Aldehyde with N,O-Acetal via N-Heterocyclic Carbene and Bronsted Acid/Base Cooperative Organocatalysis. AB - A theoretical investigation has been performed to interrogate the mechanism and stereoselectivities of aminomethylation reaction of alpha,beta-unsaturated aldehyde with N,O-acetal, which is initiated by N-heterocyclic carbene and Bronsted acid (BA). The calculated results disclose that the reaction contains several steps, i.e., formation of the actual catalysts NHC and Bronsted acid Et3N.H(+) coupled with activation of C-O bond of N,O-acetal, nucleophilic attack of NHC on alpha,beta-unsaturated aldehyde, formation of Breslow intermediate, beta-protonation for the formation of enolate intermediate, nucleophilic addition on the Re/Si face to enolate by the activated iminium cation, esterification coupled with regeneration of Et3N.H(+), and dissociation of NHC from product. Addition on the prochiral face of enolate should be the stereocontrolling step, in which the chiral alpha-carbon is formed. Furthermore, NBO, GRI, and FMO analyses have been performed to explore the roles of catalysts and origin of stereoselectivity. Surprisingly, the added Bronsted base (BB) Et3N plays an indispensable role in the esterification process, indicating the reaction proceeds under NHC-BA/BB multicatalysis rather than NHC-BA dual catalysis proposed in the experiment. This theoretical work provides a case on the exploration of the special roles of the multicatalysts in NHC chemistry, which is valuable for rational design on new cooperative organocatalysis. PMID- 27267586 TI - Selenium status in neonates with connatal infection. AB - Infectious diseases impair Se metabolism, and low Se status is associated with mortality risk in adults with critical disease. The Se status of neonates is poorly characterised, and a potential impact of connatal infection is unknown. We hypothesised that an infection negatively affects the Se status of neonates. We conducted an observational case-control study at three intensive care units at the Charite-Universitatsmedizin Berlin, Germany. Plasma samples were collected from forty-four neonates. On the basis of clinical signs for bacterial infection and concentrations of IL-6 or C-reactive protein, neonates were classified into control (n 23) and infected (n 21) groups. Plasma Se and selenoprotein P (SePP) concentrations were determined by X-ray fluorescence and ELISA, respectively, at day of birth (day 1) and 48 h later (day 3). Se and SePP showed a positive correlation in both groups of neonates. Se concentrations indicative of Se deficit in adults (500 ng/l). During antibiotic therapy, SePP increased significantly from day 1 (1.03 (sd 0.10) mg/l) to day 3 (1.34 (sd 0.10) mg/l), indicative of improved hepatic Se metabolism. We conclude that both Se and SePP are suitable biomarkers for assessing Se status in neonates and for identifying subjects at risk of deficiency. PMID- 27267587 TI - Mechanism of the Stereoselective alpha-Alkylation of Aldehydes Driven by the Photochemical Activity of Enamines. AB - Herein we describe our efforts to elucidate the key mechanistic aspects of the previously reported enantioselective photochemical alpha-alkylation of aldehydes with electron-poor organic halides. The chemistry exploits the potential of chiral enamines, key organocatalytic intermediates in thermal asymmetric processes, to directly participate in the photoexcitation of substrates either by forming a photoactive electron donor-acceptor complex or by directly reaching an electronically excited state upon light absorption. These photochemical mechanisms generate radicals from closed-shell precursors under mild conditions. At the same time, the ground-state chiral enamines provide effective stereochemical control over the enantioselective radical-trapping process. We use a combination of conventional photophysical investigations, nuclear magnetic resonance spectroscopy, and kinetic studies to gain a better understanding of the factors governing these enantioselective photochemical catalytic processes. Measurements of the quantum yield reveal that a radical chain mechanism is operative, while reaction-profile analysis and rate-order assessment indicate the trapping of the carbon-centered radical by the enamine, to form the carbon-carbon bond, as rate-determining. Our kinetic studies unveil the existence of a delicate interplay between the light-triggered initiation step and the radical chain propagation manifold, both mediated by the chiral enamines. PMID- 27267588 TI - Depression Symptoms Among Homeless Smokers: Effect of Motivational Interviewing. AB - BACKGROUND: Tobacco use is higher among homeless individuals than the general population. Homeless individuals are also more likely to have symptoms of depression. Depression symptoms may add to the burden of homelessness by increasing psychological distress and serve as a barrier to quitting smoking. OBJECTIVES: The primary goal of this study is to assess the impact of depression symptoms on psychological distress in homeless smokers. The effect of depression symptoms on abstinence and the effect of Motivational Interviewing (MI) on cessation among smokers is also explored. METHODS: Homeless smokers (N = 430) enrolled in a smoking cessation study were randomized to Motivational Interviewing (MI) or standard care (SC). Participants received nicotine replacement therapy and were followed for 26 weeks. Participants were categorized into a depression symptoms (DS) group or control group using the Patient Health Questionnaire-9. Between group differences of perceived stress, hopelessness, confidence, craving and abstinence were assessed at weeks 8 and 26. The interaction between depression symptoms (levels: DS and control) and the intervention (levels: MI and SC) was also assessed. RESULTS: Homeless smokers in the DS group reported higher levels of hopelessness, perceived stress, and craving. There was no effect of DS status on abstinence at week 8 or week 26. There was no significant interaction between depression symptoms (DS vs. Control) and the intervention (MI vs. SC). CONCLUSION: Despite reporting greater psychological distress, homeless smokers with depression symptoms in this sample had abstinence levels similar to the control group. Future research should explore protective factors among depressed smokers. PMID- 27267589 TI - Metal-Organic Frameworks as Highly Active Electrocatalysts for High-Energy Density, Aqueous Zinc-Polyiodide Redox Flow Batteries. AB - The new aqueous zinc-polyiodide redox flow battery (RFB) system with highly soluble active materials as well as ambipolar and bifunctional designs demonstrated significantly enhanced energy density, which shows great potential to reduce RFB cost. However, the poor kinetic reversibility and electrochemical activity of the redox reaction of I3(-)/I(-) couples on graphite felts (GFs) electrode can result in low energy efficiency. Two nanoporous metal-organic frameworks (MOFs), MIL-125-NH2 and UiO-66-CH3, that have high surface areas when introduced to GF surfaces accelerated the I3(-)/I(-) redox reaction. The flow cell with MOF-modified GFs serving as a positive electrode showed higher energy efficiency than the pristine GFs; increases of about 6.4% and 2.7% occurred at the current density of 30 mA/cm(2) for MIL-125-NH2 and UiO-66-CH3, respectively. Moreover, UiO-66-CH3 is more promising due to its excellent chemical stability in the weakly acidic electrolyte. This letter highlights a way for MOFs to be used in the field of RFBs. PMID- 27267590 TI - A qualitative study of how people with severe mental illness experience living in sheltered housing with a private fully equipped apartment. AB - BACKGROUND: There are a number of supported housing options for people with severe mental illness (SMI), but limited knowledge about residents' experiences. The aim of this study was to explore how people with SMI experienced sheltered housing consisting of both a private fully equipped apartment and a shared accommodation room for socializing. METHODS: Fourteen people with SMI living in sheltered housing apartments participated in a qualitative study with semi structured face to face individual or group interviews. RESULTS: Residents' access to the service providers in the sheltered housing, who were seen as both "ordinary people" and skilled to observe symptom changes at an early stage, were major factors for the perception of security. In addition, residents highlighted the possibility of living in a fully equipped apartment, and having access to a shared accommodation room to connect with other residents. Having a fully equipped apartment including their own equipment such as a washing machine was said to help reduce conflicts. Short tenancy agreements made some informants feel insecure. It was also essential to have meaningful daily activities outside the residence to avoid re-hospitalization. CONCLUSIONS: The positive experience was connected to having a fully private equipped apartment including shared accommodation room. The service providers should be aware of the dilemma with in house support, to make residents feel secure versus increased dependency on service providers. PMID- 27267591 TI - Heritability of hypothyroidism in the Finnish Hovawart population. AB - BACKGROUND: The Hovawart is a working and companion dog breed of German origin. A few hundred Hovawart dogs are registered annually in Finland. The most common disease with a proposed genetic background in Hovawarts is hypothyroidism. The disease is usually caused by lymphocytic thyroiditis, an autoimmune disorder which destroys the thyroid gland. Hypothyroidism can be treated medically with hormone replacement. Its overall incidence could also be reduced through selection, provided that the trait shows an adequate genetic basis. The aim of this study was to estimate the heritability of hypothyroidism in the Finnish Hovawart population. RESULTS: The pedigree data for the study were provided by the Finnish Kennel Club and the hypothyroidism data by the Finnish Hovawart Club. The data included 4953 dogs born between 1990 and 2010, of which 107 had hypothyroidism and 4846 were unaffected. Prior to the estimation of heritability, we studied the effects of gender, birth year, birth month, and inbreeding on susceptibility to hypothyroidism. Heritability was estimated with the probit model both via restricted maximum likelihood (REML) and Gibbs sampling, using litter and sire of the dog as random effects. None of the studied systematic effects or level of inbreeding had a significant effect on susceptibility to hypothyroidism. The estimated heritability of hypothyroidism varied from 0.47 (SE = 0.18) using REML to 0.62 (SD = 0.21) using Gibbs sampling. CONCLUSIONS: Based on our analysis, the heritability of hypothyroidism is moderate to high, suggesting that its prevalence could be decreased through selection. Thus, breeders should notify the breed association of any affected dogs, and their use for breeding should be avoided. PMID- 27267592 TI - Safety of concurrent treatment of cats with fluralaner and emodepsid praziquantel. AB - BACKGROUND: Fluralaner is a novel systemic ectoparasiticide for cats providing immediate and persistent flea- and tick-control after a single topical dose. Emodepsid and praziquantel are routinely used to control intestinal worm infections in cats. The safety of concurrent use of fluralaner and a commercially available emodepsid-praziquantel combination topical solution was investigated using topical administrations at the maximum recommended dose rates. FINDINGS: Few mild and transient clinical findings like erythema at the administration site and single incidences of salivation or vomiting were observed. All of which were consistent with the individual product leaflets. There were no findings suggesting an increased safety risk associated with the concurrent treatment of cats with fluralaner and emodepsid-praziquantel. CONCLUSIONS: Concurrent treatment with fluralaner, emodepsid and praziquantel is well tolerated in cats. PMID- 27267593 TI - Erratum to: SNP-based analysis of genetic diversity reveals important alleles associated with seed size in rice. PMID- 27267594 TI - Reducing the failure rate of hip resurfacing in dysplasia patients: a retrospective analysis of 363 cases. AB - BACKGROUND: Arthritis secondary to developmental hip dysplasia often mandates implant surgery at a relatively young age. Hip resurfacing arthroplasty (HRA), compared with standard stemmed total hip arthroplasty (THA), affords a more active lifestyle including extreme-motion activities but stimulates concerns pertaining to implant failure. METHODS: We addressed the primary modes of failure through a series of interventions, including a new guideline for achieving proper implant alignment through intraoperative x-rays. We then compared two sequential cohorts in a single-surgeon practice: patients with developmental dysplasia who underwent HRA before (Group 1; 121 hips in 105 patients) and after (Group 2; 242 hips in 210 patients) June 2008, at which time the four interventions were all in place. RESULTS: Implants in Group 2 failed less frequently within two years (0.8 % vs. 6.6 %, p = 0.002) and were more likely to have projected seven-year Kaplan Meier survivorship (99 % vs. 89 %, p < 0.0001 by log-rank test). Patients in Group 2 were more likely to have normal metal ion levels (77 % vs. 56 %, p = 0.0008) and optimum metal ion levels (99 % vs. 86 %, p = 0.0008). Patients in Group 2 also benefited from a 19-min decrease in mean operation time, a 45 % decrease in mean estimated blood loss, and a 0.9-day decrease in mean hospital stay (p < 0.0001 in each instance). CONCLUSIONS: We believe the interventions reported here, combined with sufficient surgeon experience and properly designed implants, afford patients with mild developmental dysplasia a more active lifestyle with favorable implant survival. PMID- 27267596 TI - Inclusion of the EXAMINE study in a meta-analysis of the addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia. PMID- 27267595 TI - Evaluation of custom multiplex real - time RT - PCR in comparison to fast - track diagnostics respiratory 21 pathogens kit for detection of multiple respiratory viruses. AB - BACKGROUND: Severe acute respiratory infections in children can be fatal, rapid identification of the causative agent and timely treatment can be life saving. Multiplex real time RT-PCR helps in simultaneous detection of multiple viruses saving cost, time and labour. Commercially available multiplex real time RT-PCR kits are very expensive. Therefore the aim of the present study was to develop a cost effective multiplex real time RT-PCR for the detection of 18 respiratory viruses and compare it with an in-vitro diagnostics approved Fast Track Diagnostic Respiratory Pathogens 21 Kit (FTD). METHODS: Nasopharyngeal aspirates and throat swabs were collected and processed for extraction of nucleic acid using an automated extraction system and multiplex real time RT-PCR was performed using the FTD kit and a custom assay on 356 samples. RESULTS: Custom and FTD assays detected one or more respiratory viruses in 268 (75.29 %) and 262 (73.60 %) samples respectively. The concordance between the custom assay and the FTD assay was 100 % for HCoV OC43, HCoV 229E, HPIV-1, HPIV-2, HBoV, HPeV, Flu A, and Influenza A(H1N1)pdm09 and 94.66 - 99.71 % for the remaining viruses; Flu B (99.71 %), HRV (99.71 %), HPIV-3 (98.87 %), HPIV-4 (99.43 %), HCoV NL63 (99.71 %), HMPV A/B (99.71 %), RSV A/B (94.66 %), EV (98.31 %), HCoV HKU1 (99.71 %), HAdV (99.71 %). Major discrepancy was observed for RSV A/B, which was over detected in 18 samples by the custom assay as compared to the FTD assay. The custom assay was much cheaper than the FTD assay and the time taken was only 29 min more. CONCLUSION: The custom primer and probe mix was found to be comparable to the FTD assay with good concordance but was much cheaper and the time taken for reporting was only 29 min more. The low cost custom multiplex RT-PCR can be a useful alternative to the costly FTD kit for rapid identification of viral aetiology in resource limited settings. PMID- 27267597 TI - Hospitalization and ambulatory care in imported-malaria: evaluation of trends and impact on mortality. A prospective multicentric 14-year observational study. AB - BACKGROUND: Hospitalization is usually recommended for imported malaria. The goal of the present study is to evaluate the evolution in clinical pathways while measuring their impact on mortality. METHODS: This is a 14-year prospective observational study divided into three periods. We evaluated for adult (>=15 years) and paediatric (<15 years) case trends in severity, clinical pathways (hospitalization in medical ward (MW) or intensive care unit (ICU), ambulatory care) and mortality. RESULTS: In total, 21,386 imported malaria cases were included, 4269 of them were paediatrics (20 %). Rises in severe forms for adults [from 8 % in period 1-14 % in period 3 (p = 0.0001)] and paediatrics [from 12 to 18 % (p < 0.0001)] were found. For adults, MW admission rates decreased [-15 % (CI 95 % -17; -13)] while ambulatory care [+7 % (CI 95 % 5-9)] and ICU admission rates [+4 % (CI 95 % 3-5)] increased. For paediatrics, increase in ICU admissions (+3 %) was shown. We did not observe any change in overall mortality during the study periods, whether among adults or children, regardless of care pathway. CONCLUSIONS: The present study indicates a changing management of imported malaria in adults, with an increasing trend for ambulatory care. The absence of change in mortality for adults indicates that ambulatory care can be proposed for adults presenting non-severe imported malaria. PMID- 27267598 TI - Quality of life in patients with vitiligo: a cross-sectional study based on Vitiligo Quality of Life index (VitiQoL). AB - BACKGROUND: Vitiligo is a multi-factorial pigmentary skin disorder. Recently, the importance of emotional and psychological issues is proposed in incidence, progression, relapse and remission of vitiligo. There are limited studies conducted in developing countries, which assess life quality of patients with vitiligo. The aim of this study was the application and evaluation of a disease specific quality of life index in Iranian patients, for the first time. METHODS: This cross-sectional biphasic study was conducted on 25 patients as a pilot and another 173 patients as the main study group, in Razi Hospital, Tehran, Iran, 2013-2014. Persian version of Vitiligo Quality of Life index (VitiQoL) was developed with backward-forward method. Based on the pilot study, the validity and reliability were assessed. The Vitiligo Area and Score Index (VASI), VitiQoL, and their relationship, demographic and clinical characteristic of patients were measured. RESULTS: The Mean and standard deviation of the VitiQoL score was 30.5 +/- 14.5 (range 0-60 in Persian version). There was a significant relationship between VASI score and VitiQoL (p = 0.015, r = 0.187). Confirmatory factor analysis revealed three important factors within VitiQoL: participation limitation, stigma, and behavior. In subscale analysis based on behavior factor, female patients had poorer quality of life (p = 0.02). Concomitant psychiatric problems, e.g. anxiety and depression, were not associated with QOL; however, they were near to being meaningful (p = 0.06, r = 0.14). CONCLUSION: VitiQoL is a valid index in estimating life quality of vitiligo patients and has proper relation to disease severity. Focusing on patient's life quality is an important entity in the management of vitiligo patients; relevant supportive group-based consultations and therapies are also important arms when approaching vitiligo. PMID- 27267599 TI - Pandoraea terrae sp. nov., isolated from forest soil, and emended description of the genus Pandoraea Coenye et al. 2000. AB - A Gram-staining-negative, facultatively aerobic, white-colony-forming bacterium, designated strain SE-S21T, was isolated from forest soil of Jeju Island in Korea. Cells were motile rods with a single polar flagellum, showing catalase- and oxidase-positive reactions. Growth was observed at 10-40 degrees C (optimum, 30 degrees C), pH 4.0-10.0 (optimum, pH 7.0-7.5) and with 0-4.0 % (w/v) NaCl (optimum, 0-2 %). Only ubiquinone-8 was detected as the isoprenoid quinone, and C16 : 0, C17 : 0 cyclo, C19 : 1omega8c cyclo and summed feature 2 (comprising C12 : 0 aldehyde and/or unknown) were found to be the major fatty acids. Phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, an unknown aminophospholipid, an unknown aminolipid and an unknown lipid were detected as the major polar lipids. Putrescine and 2-hydroxyputrescine were the predominant polyamines. The DNA G+C content was 61.0 mol%. Phylogenetic analyses based on 16S rRNA and DNA gyrase B gene sequences revealed that strain SE-S21T formed a phyletic lineage within the genus Pandoraea. Strain SE-S21T was most closely related to Pandoraea faecigallinarum KOxT and Pandoraea pnomenusa CCUG 38742T with 98.8 % and 98.7 % 16S rRNA gene sequence similarities, respectively. However, the DNA-DNA relatedness values between strain SE-S21T and the type strains of P. faecigallinarum and P. pnomenusa were 26.6+/-5.7 % and 20.5+/-3.7 %, respectively. On the basis of phenotypic, chemotaxonomic and molecular features, strain SE-S21T clearly represents a novel species of the genus Pandoraea, for which the name Pandoraea terrae sp. nov. is proposed. The type strain is SE-S21T (=KACC 18127T=JCM 30137T). An emended description of the genus Pandoraea is also proposed. PMID- 27267600 TI - Adverse effects of extracorporeal carbon dioxide removal (ECCO2R) for acute respiratory failure: a systematic review protocol. AB - BACKGROUND: The extracorporeal membrane carbon dioxide removal (ECCO2R) system is primarily designed for the purpose of removing CO2 from the body for patients with potentially reversible severe acute hypercapnic respiratory failure or being considered for lung transplantation. Systematic reviews have focused on the effectiveness of ECCO2R. To the author's best knowledge, this is the first systematic review to focus on the adverse effects of this procedure. METHODS: We will conduct a systematic review of procedure-related adverse effects of ECCO2R systems. A high sensitivity search strategy will be employed in Cochrane Library, MEDLINE, EMBASE, Web of Science and product regulatory databases and ongoing trial registers to identify citations. Reference lists of relevant studies and grey literature will also be searched. Screening of the results will be performed by two reviewers independently using pre-defined inclusion and exclusion criteria. Clinical trials and observational studies will be included. Data will be extracted using a purposefully developed extraction form. Appropriateness for statistical pooling of the results will be determined and carried out if heterogeneity is low to moderate. The GRADE framework will be employed to grade the overall quality of the evidence. DISCUSSION: In the UK, the current access to the use of ECCO2R is possible only with special arrangements for clinical governance, consent and for audit or research. Current evidence on ECCO2R suggests that there are a number of well-recognised complications which vary greatly across studies. This systematic review will consolidate the existing knowledge on adverse effects resulting from the use of ECCO2R. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023503 . PMID- 27267601 TI - Characteristics of bacterial pathogens associated with acute diarrhea in children under 5 years of age: a hospital-based cross-sectional study. AB - BACKGROUND: Acute diarrhea is a leading cause of morbidity and mortality in children, particularly in those under the age of 5 years. Rotavirus is recognized as the leading cause of acute diarrhea in children, however, the contribution of bacterial pathogens as causative agents varies throughout the world. Here we report a hospital-based prospective study to analyze the characteristics of bacterial pathogens associated with acute diarrhea in children under 5 years of age. METHODS: Stool samples were collected from 508 patients with acute diarrhea under 5 years of age who presented at our hospital. Nine pathogens were isolated and identified by culturing, serology or PCR, these included Salmonella spp., Shigella spp., Vibrio cholerae, diarrheagenic Escherichia coli (DEC), Aeromonas spp., Plesiomonas spp., Vibrio parahaemolyticus, Campylobacter spp. and Yersinia enterocolitica. Antimicrobial sensitivity tests of these pathogens were conducted. The most commonly detected pathogen, Salmonella spp., was further investigated by PCR and sequencing of antibiotic resistance-related genes. RESULTS: Pathogens were identified in 20.1 % of the 508 samples. The most commonly detected pathogens were Salmonella spp. (8.5 %), followed by DEC (4.7 %), Campylobacter jejuni (3.0 %) and Aeromonas spp. (2.0 %). The resistance rates to ampicillin and tetracycline in Salmonella spp. were >60 %, but were <30 % to cephalosporins and quinolones. More than 50 % of DEC strains displayed resistance to ampicillin, cefotaxime and tetracycline, and 60 % of C. jejuni strains were resistant to ciprofloxacin but highly sensitive to the other antibiotics. Among 12 cephalosporin-resistant Salmonella isolates, TEM-1 and CTX-M-14 determinants were present in two (16.7 %) isolates. PCR screening for plasmid-mediated quinolone resistance genes revealed gyrA mutations in one of three highly quinolone resistant isolates. CONCLUSIONS: Salmonella spp., DEC, Campylobacter spp. and Aeromonas spp. were the most commonly detected bacterial pathogens in children under the age of 5 years with acute diarrhea. Our findings indicate that ampicillin and tetracycline are not suitable as first line therapeutic drugs against Salmonella spp. Resistance to third generation cephalosporins and quinolones was also detected. TEM-1 and CTX-M-14 genetic determinants, and gyrA mutations, were the major mechanisms associated with high levels of cephalosporin and quinolone resistance, respectively, in Salmonella isolates. PMID- 27267602 TI - Time to publication among completed diagnostic accuracy studies: associated with reported accuracy estimates. AB - BACKGROUND: Previous evaluations have documented that studies evaluating the effectiveness of therapeutic interventions are not always reported, and that those with statistically significant results are published more rapidly than those without. This can lead to reporting bias in systematic reviews and other literature syntheses. We evaluated whether diagnostic accuracy studies that report promising results about the performance of medical tests are also published more rapidly. METHODS: We obtained all primary diagnostic accuracy studies included in meta-analyses of Medline-indexed systematic reviews that were published between September 2011 and January 2012. For each primary study, we extracted estimates of diagnostic accuracy (sensitivity, specificity, Youden's index), the completion date of participant recruitment, and the publication date. We calculated the time from completion to publication and assessed associations with reported accuracy estimates. RESULTS: Forty-nine systematic reviews were identified, containing 92 meta-analyses and 924 unique primary studies, of which 756 could be included. Study completion dates were missing for 285 (38 %) of these. Median time from completion to publication in the remaining 471 studies was 24 months (IQR 16 to 35). Primary studies that reported higher estimates of sensitivity (Spearman's rho = -0.14; p = 0.003), specificity (rho = -0.17; p < 0.001), and Youden's index (rho = -0.22; p < 0.001) had significantly shorter times to publication. When comparing time to publication in studies reporting accuracy estimates above versus below the median, the median number of months was 23 versus 25 for sensitivity (p = 0.046), 22 versus 27 for specificity (p = 0.001), and 22 versus 27 for Youden's index (p < 0.001). These differential time lags remained significant in multivariable Cox regression analyses with adjustment for other study characteristics, with hazard ratios of publication of 1.06 (95 % CI 1.02 to 1.11; p = 0.007) for logit-transformed estimates of sensitivity, 1.09 (95 % CI 1.04 to 1.14; p < 0.001) for logit-transformed estimates of specificity, and 1.09 (95 % CI 1.03 to 1.14; p = 0.001) for logit transformed estimates of Youden's index. CONCLUSIONS: Time to publication was significantly shorter for studies reporting higher estimates of diagnostic accuracy compared to those reporting lower estimates. This suggests that searching and analyzing the published literature, rather than all completed studies, can produce a biased view of the performance of medical tests. PMID- 27267603 TI - Using eye tracking and gaze pattern analysis to test a "dirty bomb" decision aid in a pilot RCT in urban adults with limited literacy. AB - BACKGROUND: Eye tracking is commonly used in marketing to understand complex responses to materials, but has not been used to understand how low-literacy adults access health information or its relationship to decision making. METHODS: This study assessed how participants use a literacy appropriate "dirty bomb" decision aid. Participants were randomized to receive a CDC "factsheet" (n = 21) or literacy-appropriate aid (n = 29) shown on a computer screen. Using 7 content similar slides, gaze patterns, mean pupil fixation time and mean overall time reading and looking at slides were compared. Groups were also compared by literacy level and effect on 'confidence of knowledge' and intended behavior. RESULTS: Results revealed differing abilities to read densely written material. Intervention participants more precisely followed text on 4 of 7 content-similar slides compared to control participants whose gaze patterns indicated unread text, or repeated attempts at reading the same text, suggesting difficulty in understanding key preparedness messages. Controls had significantly longer pupil fixations on 5 of 7 slides and spent more overall time on every slide. In those with very low literacy, intervention participants were more likely than controls to say they understood what a "dirty bomb" is and how to respond if one should occur. CONCLUSIONS: Results indicate limited- literacy adults, especially those with very low literacy, may not be able to understand how to respond during a "dirty bomb" using available materials, making them vulnerable to negative health events. This study provides insights into how individuals perceive and process risk communication messages, illustrating a rich and nuanced understanding of the qualitative experience of a limited literacy population with written materials. It also demonstrates the feasibility of using these methods on a wider scale to develop more effective health and risk communication messages designed to increase knowledge of and compliance with general health guidelines, and enhance decision making. This has application for those with learning disabilities, those with limited media-literacy skills, and those needing to access the diverse array of assistive technologies now available. Eye tracking is thus a practical approach to understanding these diverse needs to ensure the development of cogent and salient communication. PMID- 27267604 TI - Dynamical Interactions of 5-Fluorouracil Drug with Dendritic Peptide Vectors: The Impact of Dendrimer Generation, Charge, Counterions, and Structured Water. AB - Molecular dynamics simulations are utilized to investigate the interactions between the skin cancer drug 5-fluorouracil (5FU) and peptide-based dendritic carrier systems. We find that these drug-carrier interactions do not conform to the traditional picture of long-time retention of the drug within a hydrophobic core of the dendrimer carrier. Rather, 5FU, which is moderately soluble in its own right, experiences weak, transient chattering interactions all over the dendrimer, mediated through multiple short-lived hydrogen bonding and close contact events. We find that charge on the periphery of the dendrimer actually has a negative effect on the frequency of drug-carrier interactions due to a counterion screening effect that has not previously been observed. However, charge is nevertheless an important feature since neutral dendrimers are shown to have a significant mutual attraction that can lead to clustering or agglomeration. This clustering is prevented due to charge repulsion for the titrated dendrimers, such that they remain independent in solution. PMID- 27267605 TI - SGK-1 and PHLPP1: Ras-mediated effectors during ECM-detachment. PMID- 27267606 TI - Blindness, cataract surgery and mortality in Ethiopia. AB - PURPOSE: To examine the relationships between blindness, the intervention of cataract surgery and all-cause mortality in a rural Ethiopian population. DESIGN: Population-based, interventional prospective study. METHODS: Community-based detection methods identified blind Ethiopian persons from two selected kebeles in Amhara region, Ethiopia. Data from 1201 blind patients were collected-628 cataract-blind and 573 blind from other conditions. Free cataract surgery was provided for consenting, cataract-blind patients. Follow-up surveys were conducted after 12 months (+/-1 month)-the main outcome measure for this report is all-cause mortality at 1 year. RESULTS: During the follow-up period, 110 persons died from the selected population (mortality 9.2%), which consisted of those cataract-blind patients who received cataract surgery (N=461), cataract blind patients who did not receive surgery (N=167) and all non-cataract-blind patients (N=573). Of the 461 patients who received cataract surgery, 44 patients died (9.5%). Of the 740 patients who did not receive surgery, 66 died (8.9%)-28 patients from the cohort of cataract-blind patients who did not receive surgery (16.8%) and 38 patients from the cohort of non-cataract blind (6.6%). Subgroup analysis revealed significantly increased odds of mortality for cataract-blind patients over 75 years of age who did not receive surgery and for unmarried patients of all age groups. CONCLUSIONS: In this population, mortality risk was significantly elevated for older cataract-blind patients when compared with non cataract-blind patients-an elevation of risk that was not noted in an age-matched cohort of cataract-blind patients who underwent cataract surgery as early as 1 year follow-up. PMID- 27267607 TI - Do visually impaired children and their parents agree on the child's vision related quality of life and functional vision? AB - AIMS: To investigate agreement between children with visual impairment (VI) and their parents on their ratings of the child's vision-related quality of life (VQoL) and functional vision (FV) using two novel self-report patient-reported outcome measures developed for this population. METHODS: 99 children aged 10-15 years (mean age=12.2, SD=1.9) with VI (best corrected acuity (logarithm of the minimum angle of resolution) 0.50 or worse in better eye) and their parents participated in a national postal survey, completing the child and proxy versions of our novel instruments assessing VQoL and FV of children with VI-the vision related quality of life instrument for children and young people (VQoL_CYP) and the functional vision questionnaire for children and young people (FVQ_CYP), respectively. Parent-child agreement was investigated using the Bland-Altman (BA) method. Variation across key sociodemographic and clinical characteristics was examined using the Intraclass Correlation Coefficient. RESULTS: Average parental ratings of their child's VQoL and FV were significantly lower than the children's own ratings, but the range of disagreement was wide, with parents both overestimating and underestimating their child's VQoL (mean score difference=5.7, BA limits of agreement (LOA): lower -22.10 (CI 95% -24.61 to 19.59) and upper 33.50 (CI 95% 30.99 to 36.01)), but more consistently underestimating the child's FV (mean score difference=-11.8, BA LOA: lower -39.60 (CI 95% -42.12 to 37.08) and upper 16 (CI 95% 13.48 to 18.52)). There was variation in agreement by some child characteristics, including vision level, time of onset and course of VI progression. CONCLUSIONS: Visually impaired children and their parents perceive the broader impact of living with VI very differently. There is value in routine capture of information independently from children and their parents for comprehensively gauging the impact of childhood VI and tailoring appropriate interventions. PMID- 27267609 TI - Good outcomes for lymphoma treatment during pregnancy. PMID- 27267610 TI - Trends in immunotherapy for brain metastases. PMID- 27267611 TI - Long waiting times for test results for NHS patients. PMID- 27267608 TI - Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. AB - BACKGROUND: Immunotherapy targeting the PD-1 axis has activity in several tumour types. We aimed to establish the activity and safety of the PD-1 inhibitor pembrolizumab in patients with untreated brain metastases from melanoma or non small-cell lung cancer (NSCLC). METHODS: In this non-randomised, open-label, phase 2 trial, we enrolled patients aged 18 years or older with melanoma or NSCLC with untreated brain metastases from the Yale Cancer Center. Patients had at least one untreated or progressive brain metastasis between 5 and 20 mm in diameter without associated neurological symptoms or the need for corticosteroids. Patients with NSCLC had tumour tissue positive for PD-L1 expression; this was not required for patients with melanoma. Patients were given 10 mg/kg pembrolizumab every 2 weeks until progression. The primary endpoint was brain metastasis response assessed in all treated patients. The trial is ongoing and here we present an early analysis. The study is registered with ClinicalTrials.gov, number NCT02085070. FINDINGS: Between March 31, 2014, and May 31, 2015, we screened 52 patients with untreated or progressive brain metastases (18 with melanoma, 34 with NSCLC), and enrolled 36 (18 with melanoma, 18 with NSCLC). A brain metastasis response was achieved in four (22%; 95% CI 7-48) of 18 patients with melanoma and six (33%; 14-59) of 18 patients with NSCLC. Responses were durable, with all but one patient with NSCLC who responded showing an ongoing response at the time of data analysis on June 30, 2015. Treatment-related serious and grade 3-4 adverse events were grade 3 elevated aminotransferases (n=1 [6%]) in the melanoma cohort, and grade 3 colitis (n=1 [6%]), grade 3 pneumonitis (n=1 [6%]), grade 3 fatigue (n=1 [6%]), grade 4 hyperkalemia (n=1 [6%]), and grade 2 acute kidney injury (n=1 [6%]) in the NSCLC cohort. Clinically significant neurological adverse events included transient grade 3 cognitive dysfunction and grade 1-2 seizures (n=3 [17%]) in the melanoma cohort. INTERPRETATION: Pembrolizumab shows activity in brain metastases in patients with melanoma or NSCLC with an acceptable safety profile, which suggests that there might be a role for systemic immunotherapy in patients with untreated or progressive brain metastases. FUNDING: Merck and the Yale Cancer Center. PMID- 27267612 TI - Stronger correlation of surrogate endpoints with survival needed. PMID- 27267613 TI - Digestive Disease Week 2016. PMID- 27267614 TI - Transplanting Sensitized Kidney Transplant Patients With Equivalent Outcomes Utilizing Stringent HLA Crossmatching. AB - OBJECIVES: Elevated panel reactive antibody levels have been traditionally associated with increased acute rejection rate and decreased long-term graft survival after kidney transplant. In this study, our objective was to determine patient and allograft outcomes in sensitized kidney transplant recipients with advanced HLA antibody detection and stringent protein sequence epitope analyses. MATERIALS AND METHODS: This was a subanalysis of a prospective, risk-stratified randomized controlled trial that compared interleukin 2 receptor antagonist to rabbit antithymocyte globulin induction in 200 kidney transplant recipients, examining outcomes based on panel reactive antibody levels of < 20% (low) versus >= 20% (high, sensitized). The study was conducted between February 2009 and July 2011. All patients underwent solid-phase single antigen bead assays to detect HLA antibodies and stringent HLA epitope analyses with protein sequence alignment for virtual crossmatching. Delayed graft function, acute rejection rates, and graft loss were the main outcomes measured. RESULTS: Both the low (134 patients) and high (66 patients) panel reactive antibody level cohorts had equivalent induction and maintenance immunosuppression. Patients in the high-level group were more likely to be female (P < .001), African American (P < .001), and received a kidney from a deceased donor (P = .004). Acute rejection rates were similar between the low (rate of 8%) and high (rate of 9%) panel reactive antibody groups (P = .783). Delayed graft function, borderline rejection, graft loss, and death were not different between groups. Multivariate analyses demonstrated delayed graft function to be the strongest predictor of acute rejection (odds ratio, 5.7; P = .005); panel reactive antibody level, as a continuous variable, had no significant correlation with acute rejection (C statistic, 0.48; P = .771). CONCLUSIONS: Appropriate biologic matching with single antigen bead assays and stringent epitope analyses provided excellent outcomes in sensitized patients regardless of the induction therapy choice. PMID- 27267615 TI - Variation in induction of labour rates across Irish hospitals; a cross-sectional study. AB - BACKGROUND: In developed countries, rates of induction of labour (IOL) have increased and vary between hospitals. We aimed to identify whether national variations could be explained by sociodemographic, clinical and organisational differences. METHODS: Two national databases in Ireland that routinely collect clinical and administrative data, the National Perinatal Reporting System and the Hospital Inpatient Enquiry Scheme, were used to analyse data for all women with singleton births weighing >=500 g in 2009. We used logistic multilevel models to examine variation between hospitals, and to determine how much variation was due to individual level sociodemographic, clinical and organisational variables. Analyses were stratified for nulliparas, multiparas without prior caesarean section (CS) and multiparas with prior CS. RESULTS: Of 69 304 eligible births, the rate of IOL nationally was 25.0% (range 14.5-33.2%).In nulliparas, the mean rate was 30.9% (range 18.6-45.7%). The rate was 24.8% (13.5-33.3%) and 3.8% (0.0 10.2%) for multiparas without and with prior CS, respectively. In nulliparas and multiparas without prior CS IOL was predicted by maternal birth in Ireland, increasing birthweight, antepartum complications, giving birth on a weekday and the model of obstetric care. Even after adjusting for known sociodemographic and clinical variables, variation between hospitals remained. CONCLUSION: We found that clinical, sociodemographic and organisational factors all contributed to variation. However, unexplained variation persisted possibly due to organisational factors such as hospital-specific policies on IOL. The results indicate that the prevalence of antenatal complications, changing immigration patterns and policies on IOL after previous CS are factors likely to influence future IOL rates. PMID- 27267616 TI - Optimal insecticide-treated bed-net coverage and malaria treatment in a malaria HIV co-infection model. AB - We propose and study a mathematical model for malaria-HIV co-infection transmission and control, in which malaria treatment and insecticide-treated nets are incorporated. The existence of a backward bifurcation is established analytically, and the occurrence of such backward bifurcation is influenced by disease-induced mortality, insecticide-treated bed-net coverage and malaria treatment parameters. To further assess the impact of malaria treatment and insecticide-treated bed-net coverage, we formulate an optimal control problem with malaria treatment and insecticide-treated nets as control functions. Using reasonable parameter values, numerical simulations of the optimal control suggest the possibility of eliminating malaria and reducing HIV prevalence significantly, within a short time horizon. PMID- 27267618 TI - What should we do NOW? Review of a large NHS Trust's meticillin-resistant Staphylococcus aureus screening. PMID- 27267617 TI - From microbiology to cell biology: when an intracellular bacterium becomes part of its host cell. AB - Mitochondria and chloroplasts are now called organelles, but they used to be bacteria. As they transitioned from endosymbionts to organelles, they became more and more integrated into the biochemistry and cell biology of their hosts. Work over the last 15 years has shown that other symbioses show striking similarities to mitochondria and chloroplasts. In particular, many sap-feeding insects house intracellular bacteria that have genomes that overlap mitochondria and chloroplasts in terms of size and coding capacity. The massive levels of gene loss in some of these bacteria suggest that they, too, are becoming highly integrated with their host cells. Understanding these bacteria will require inspiration from eukaryotic cell biology, because a traditional microbiological framework is insufficient for understanding how they work. PMID- 27267619 TI - A cross-sectional survey of environmental health in remote Aboriginal communities in Western Australia. AB - INTRODUCTION: The Australian Aboriginal population experiences significantly poorer health than the non-Aboriginal population. The contribution of environmental risk factors in remote communities to this health disparity is poorly understood. OBJECTIVE: To describe and quantify major environmental risk factors and associated health outcomes in remote Aboriginal communities in Western Australia. METHODS: The association between environmental health indicators, community infrastructure and reported health outcomes was analysed using linear and logistic regression of survey data. RESULTS: Housing/overcrowding was significantly associated with increased reports of hearing/eyesight (OR 3.01 95 % CI 1.58-5.73), skin (OR 2.71 95 % CI 1.31-5.60), gastrointestinal (OR 3.51 95 % CI 1.49-8.26) and flu/colds (OR 2.47 95 % CI 1.27 4.78) as health concerns. Dust was significantly associated with hearing/eyesight (OR 3.16 95 % CI 1.82-5.48), asthma/respiratory (OR 2.48 95 % CI 1.43-4.29) and flu/colds (OR 3.31 95 % CI 1.88-5.86) as health concerns. CONCLUSION: Poor environmental health is prevalent in remote Aboriginal communities and requires further delineation to inform environmental health policy. PMID- 27267620 TI - Visualizing and Clustering Protein Similarity Networks: Sequences, Structures, and Functions. AB - Research in the recent decade has demonstrated the usefulness of protein network knowledge in furthering the study of molecular evolution of proteins, understanding the robustness of cells to perturbation, and annotating new protein functions. In this study, we aimed to provide a general clustering approach to visualize the sequence-structure-function relationship of protein networks, and investigate possible causes for inconsistency in the protein classifications based on sequences, structures, and functions. Such visualization of protein networks could facilitate our understanding of the overall relationship among proteins and help researchers comprehend various protein databases. As a demonstration, we clustered 1437 enzymes by their sequences and structures using the minimum span clustering (MSC) method. The general structure of this protein network was delineated at two clustering resolutions, and the second level MSC clustering was found to be highly similar to existing enzyme classifications. The clustering of these enzymes based on sequence, structure, and function information is consistent with each other. For proteases, the Jaccard's similarity coefficient is 0.86 between sequence and function classifications, 0.82 between sequence and structure classifications, and 0.78 between structure and function classifications. From our clustering results, we discussed possible examples of divergent evolution and convergent evolution of enzymes. Our clustering approach provides a panoramic view of the sequence-structure-function network of proteins, helps visualize the relation between related proteins intuitively, and is useful in predicting the structure and function of newly determined protein sequences. PMID- 27267621 TI - Quantified degree of poultry exposure differs for human cases of avian influenza H5N1 and H7N9. AB - Preliminary evidence suggests that direct poultry contact may play a lesser role in transmission of avian influenza A(H7N9) than A(H5N1) to humans. To better understand differences in risk factors, we quantified the degree of poultry contact reported by H5N1 and H7N9 World Health Organization-confirmed cases. We used publicly available data to classify cases by their degree of poultry contact, including direct and indirect. To account for potential data limitations, we used two methods: (1) case population method in which all cases were classified using a range of sources; and (2) case subset method in which only cases with detailed contact information from published research literature were classified. In the case population, detailed exposure information was unavailable for a large proportion of cases (H5N1, 54%; H7N9, 86%). In the case subset, direct contact proportions were higher in H5N1 cases (70.3%) than H7N9 cases (40.0%) (chi 2 = 18.5, P < 0.001), and indirect contact proportions were higher in H7N9 cases (44.6%) than H5N1 cases (19.4%) (chi 2 = 15.5, P < 0.001). Together with emerging evidence, our descriptive analysis suggests direct poultry contact is a clearer risk factor for H5N1 than for H7N9, and that other risk factors should also be considered for H7N9. PMID- 27267622 TI - Comparative proteomic analysis reveals intracellular targets for bacillomycin L to induce Rhizoctonia solani Kuhn hyphal cell death. AB - Bacillomycin L, a natural iturinic lipopeptide produced by Bacillus amyloliquefaciens, is characterized by strong antifungal activity against a variety of agronomically important filamentous fungi including Rhizoctonia solani Kuhn. To further understand its antifungal actions, proteomes were comparatively studied within R. solani hyphal cells treated with or without bacillomycin L. The results show that 39 proteins were alternatively expressed within cells in response to this lipopeptide, which are involved in stress response, carbohydrate, amino acid and nucleotide metabolism, cellular component organization, calcium homeostasis, protein degradation, RNA processing, gene transcription, and others, suggesting that, in addition to inducing cell membrane permeabilization, iturin exhibits antibiotic activities by targeting intracellular molecules. Based on these results, a model of action of bacillomycin L against R. solani hyphal cells was proposed. Our study provides new insight into the antibiotic mechanisms of iturins. PMID- 27267623 TI - Intact spore MALDI-TOF mass spectrometry and proteomic analysis of Puccinia pathogenic fungi. AB - The aim of this work was to develop a method for the identification of pathogens causing rust diseases of crops using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) of intact cells or spores (IC/IS). All optimizations were performed with Puccinia triticina, the causal agent of wheat leaf rust. Experiments included selection of washing solvents for spores, finding of an optimal concentration of spores in suspension and the most suitable matrix system as well as an evaluation of different sample preparation techniques. The best results were obtained when the spores were washed with acetonitrile/0.1% (v/v) trifluoroacetic acid, 7:3, v/v. A mixture of ferulic and sinapinic acids (5:15mgml(-1)) dissolved in acetonitrile/2.5% (v/v) trifluoroacetic acid, 7:3, v/v, was found optimal for the deposition of samples (50MUg spores per MUl) by two-layer volume technique. The optimized protocol was subsequently applied to other Puccinia species (Puccinia graminis, Puccinia striiformis and Puccinia coronata). Together with the use of the software BIOSPEAN, not only different species but also various pathotypes of the same species, which differ in their virulence, could be discriminated. There were 108 and 29 proteins identified from P. striiformis and P. graminis spores, respectively, after an acidic extraction in the matrix solvent mimicking the sample preparation for MALDI. Besides the presence of ribosomal proteins, histones, regulatory proteins and enzymes, also extracellular proteins participating in the pathogenesis were found. Finally, for both species, several proteins were assigned to signals in typical mass spectrometric profiles and suggested as diagnostic markers. PMID- 27267624 TI - Media Use by Children, and Parents' Views on Children's Media Usage. AB - BACKGROUND: New (mobile phones, smartphones, tablets, and social media) and traditional media (television) have come to dominate the lives of many children and adolescents. Despite all of this media time and new technology, many parents seem to have few rules regarding the use of media by their children and adolescents. OBJECTIVES: The aim of this study was to evaluate media access/use of children and to evaluate beliefs and attitudes of parents concerning the use of old and new media in Turkey. METHODS: This is a cross-sectional electronic survey of a national convenience sample in Turkey via SurveyMonkey, including 41 questions regarding topics relevant to television, computers, mobile phones, iPad/tablet use, and social media accounts. RESULTS: The responses of the 333 participants (238 women, 95 men; 27-63 years) were evaluated. The average daily watching alone time was 0 to 2 hours among 53.4% (46/86), and daily coviewing time with parents of children was 0 to 2 hours among 62.7% (54/86) of children below 2 years of age. Regarding parents' monitoring their children's computer use (n=178), 35.4% (63/178) of the parents prefer coviewing, 13.5% of the parents use a family filter (24/178), and 33.1% (59/178) of the parents prefer to check Web history. Approximately 71.2% (237/333) of the participants had an iPad/tablet in the house, 84.3% (200/333) of the parents give their children permission to use the iPad/tablet. Of the parents, 22.5% (45/200) noted that their children used the iPad/tablet at the table during lunch/dinner and 57.9% (26/45) of these children were aged 5 years and below. Of parents, 27.3% (91/333) agreed that the optimal age for owning a mobile phone was 12 years, and 18.0% (60/333) of the parents noted that their children (one-third was below 2 years) used the mobile phone at the table during meals. A total of 33.3% (111/333) children/adolescents have a Facebook profile, and 54.0% (60/111) were below 13 years of age. Approximately 89.2% (297/333) of the parents emphasized that the Internet is essential for their child's education. DISCUSSION: According to our study results, knowledge regarding the use of old and new media is limited among the parents in Turkey. Our study showed that screen time and mobile device use (including during meals) are common in children below 2 years of age, whereas no screen time was recommended for children below 2 years of age. We concluded that there is need for evidence-based guidelines regarding the use of the Internet and social media for parents and parents should ensure that there is a plan in place for the use of children's media. PMID- 27267625 TI - Aminoflavone-loaded EGFR-targeted unimolecular micelle nanoparticles exhibit anti cancer effects in triple negative breast cancer. AB - Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer for which there is no available targeted therapy. TNBC cases contribute disproportionately to breast cancer-related mortality, thus the need for novel and effective therapeutic methods is urgent. We have previously shown that a National Cancer Institute (NCI) investigational drug aminoflavone (AF) exhibits strong growth inhibitory effects in TNBC cells. However, in vivo pulmonary toxicity resulted in withdrawal or termination of several human clinical trials for AF. Herein we report the in vivo efficacy of a nanoformulation of AF that enhances the therapeutic index of AF in TNBC. We engineered a unique unimolecular micelle nanoparticle (NP) loaded with AF and conjugated with GE11, a 12 amino acid peptide targeting epidermal growth factor receptor (EGFR), since EGFR amplification is frequently observed in TNBC tumors. These unimolecular micelles possessed excellent stability and preferentially released drug payload at endosomal pH levels rather than blood pH levels. Use of the GE11 targeting peptide resulted in enhanced cellular uptake and strong growth inhibitory effects in TNBC cells. Further, AF-loaded, GE11-conjugated (targeted) unimolecular micelle NPs significantly inhibit orthotopic TNBC tumor growth in a xenograft model, compared to treatment with AF-loaded, GE11-lacking (non-targeted) unimolecular micelle NPs or free AF. Interestingly, the animals treated with AF loaded, targeted NPs had the highest plasma and tumor level of AF among different treatment groups yet exhibited no increase in plasma aspartate aminotransferase (AST) activity level or observable tissue damage at the time of sacrifice. Together, these results highlight AF-loaded, EGFR-targeted unimolecular micelle NPs as an effective therapeutic option for EGFR-overexpressing TNBC. PMID- 27267626 TI - 808 nm Light-triggered and hyaluronic acid-targeted dual-photosensitizers nanoplatform by fully utilizing Nd(3+)-sensitized upconversion emission with enhanced anti-tumor efficacy. AB - The current near-infrared (NIR) light-induced photodynamic therapy (PDT) can enhance the tissue penetration depth to trigger photosensitizers (PSs) far from the surface. NIR-mediated PDT is still challenged by overheating effect on normal tissues, limited tumor selectivity and low reactive oxygen species (ROS) yields. Here we construct a dual-agent photosensitizing nanoplatform by combining UV-blue upconversion emitting NaYF4:Yb/Tm@NaYF4:Yb@NaNdF4:Yb@NaYF4 (labeled as UCNPs) multi-shell nanocrystals with titanium dioxide (TiO2, UV-light-excited PS) and hypocrellin A (HA, blue-light-excited PS), which can induce cancer cell apoptosis by 808 nm light-triggered and hyaluronic acid (Hyal)-targeted PDT. In this construction strategy, the crystallized TiO2 shells on the surface of UCNPs can play dual roles as UV-light excited PS and conjugation site for Hyal, and then Hyal is served as targeting-ligand as well as the carrier of HA simultaneously. The step-by-step reactive mode of loading PSs and modifying targeting-ligands is a controllable and ordered design based on the use of one intermediate product as the reaction site for the next component. The Nd(3+)-sensitized UCNPs with quenching reduction layer can efficiently convert 808 nm NIR light to UV-blue emission for simultaneous activation of two PSs with enhanced intracellular ROS generation. Through the in vitro and in vivo experiment results, the dual photosensitizers nanoplatform presents enhanced anti-tumor efficacy by effective targeting cellular uptake and taking full advantage of upconversion emission, which may make a major step toward next generation of NIR-mediated PDT. PMID- 27267627 TI - Peptide inhibition of p22phox and Rubicon interaction as a therapeutic strategy for septic shock. AB - Sepsis is a clinical syndrome that complicates severe infection and is characterized by the systemic inflammatory response syndrome (SIRS), is a life threatening disease characterized by inflammation of the entire body. Upon microbial infection, p22phox-gp91phox NADPH oxidase (NOX) complexes produce reactive oxygen species (ROS) that are critical for the elimination of invading microbes. However, excess production of ROS represents a key element in the cascade of deleterious processes in sepsis. We have previously reported direct crosstalk between autophagy and phagocytosis machineries by demonstrating that the Rubicon protein interacts with p22phox upon microbial infection, facilitating phagosomal trafficking of the p22phox-gp91phox NOX complex to induce a ROS burst, inflammatory cytokine production, and thereby, potent anti-microbial activities. Here, we showed N8 peptide, an N-terminal 8-amino acid peptide derived from p22phox, was sufficient for Rubicon interaction and thus, capable of robustly blocking the Rubicon-p22phox interaction and profoundly suppressing ROS and inflammatory cytokine production. Consequently, treatment with the Tat-N8 peptide or a N8 peptide-mimetic small-molecule dramatically reduced the mortality associated with Cecal-Ligation-and-Puncture-induced polymicrobial sepsis in mice. This study demonstrates a new anti-sepsis therapeutic strategy by blocking the crosstalk between autophagy and phagocytosis innate immunity machineries, representing a potential paradigm shift for urgently needed therapeutic intervention against this life-threatening SIRS. PMID- 27267628 TI - Synergistic targeting tenascin C and neuropilin-1 for specific penetration of nanoparticles for anti-glioblastoma treatment. AB - The pathological and physiological barriers of glioblastoma multiforme (GBM) lead to insufficient extravasation and penetration of nano-sized therapeutics. As the main driver of interstitial fluid pressure-related drug efflux, the aberrant extracellular matrix (ECM) appears to be a valuable target that plays a crucial role in forming pathological barriers of GBM. Herein, a new Ft peptide was synthesized by coupling FHK and tLyp-1 sequence together via a cysteine to synergistically target glioma-associated tenascin C (extracellular matrix component) and neuropilin-1 on neovasculature and glioma cells to enable specific penetration of nanoparticles for anti-glioblastoma treatment. In vitro, Ft peptide-functionalization not only enabled the internalization of poly (ethyleneglycol)-poly (lactic acid) nanoparticulate system in 2D U87 MG cells and HUVEC cells but also facilitated its deep penetration in 3D glioma spheroids. Similarly, in vivo real-time 2D and 3D imaging clearly showed a substantial accumulation of the Ft-functionalized nanoparticles (Ft-NP) in the glioma foci of intracranial U87 glioma-bearing mice. Glioma distribution assay demonstrated a tenascin C-mediated accumulation in glioma foci and neuropilin-1-mediated transportation through glioma cells. Paclitaxel-loaded Ft-NP (Ft-NP-PTX) induced higher cytotoxic effect and apoptosis rate compared with FHK or tLyp-1-modified ones. The highest anti-glioma efficacy was also achieved following the i.v. administration of Ft-NP-PTX, with a median survival promotion of 269% than that of the saline-treated mice, while only limited life span promotion was obtained after the treatment of other formulations (31.3%, 59.4%, 134.4% and 109.3% respectively for Taxol((r)), NP-PTX, tLyp-1-NP-PTX and FHK-NP-PTX). In conclusion, all these evidences together verified the improved therapeutic effect of Ft-NP-PTX for anti-glioma drug delivery via neuropilin-1- and tenascin C mediated specific penetration of nanoparticles in to glioma parenchyma. PMID- 27267629 TI - Transparent, resilient human amniotic membrane laminates for corneal transplantation. AB - This study evaluated a new technique to toughen and optically clarify human amniotic membrane (AM) tissue, which is naturally thin and clouded, and determined the suitability of the altered tissue for corneal transplantation. The technique created a tissue laminate by repeatedly depositing wet layers of AM and dehydrating them, followed by chemical cross-linking to tighten integration at the layer interfaces and within the layers, thereby improving the physical properties of the laminates by increasing light transmittance and mechanical strength. Interestingly, this improvement only occurred in laminates with at least 4 layers. Cross-linking also improved the resistance of the laminates to collagenase degradation, such as occurs in corneal melting. This study also confirmed that the AM tissue was biocompatible by inserting AM monolayers into the corneal stroma of rabbits, and by performing lamellar keratoplasty in rabbits with cross-linked AM laminates. The laminates were sufficiently thick and resilient to need only one set of sutures, whereas in previously described multi layer AM transplantation technique, each layer required separate sutures. The current findings are a promising advance in the engineering of novel biomaterials and the alteration of existing tissues for medical use. PMID- 27267630 TI - Endogenous human skin equivalent promotes in vitro morphogenesis of follicle-like structures. AB - Three-dimensional constructs formed by cells embedded in an exogenous scaffold could not represent a faithful in vitro replica of native and functional tissues. In this work we produced an endogenous human skin equivalent by means of a tissue engineering process that induces the full morphogenesis of functional dermal and epidermal compartments. In such an organotypic context we demonstrated that -by using adult human skin cells-it is possible to generate follicle-like structures in vitro resembling what occurs in vivo in the fetal skin. Immunotypization evidences an inward-oriented differentiation of the follicular-like structures through immunopositivity for epithelial stem cell markers such as p63 and K19. Moreover we detected the presence of versican within the intricate network of the dermal compartment, suggesting its role as an inductive factor for the morphogenesis of appendage-like structures. These results support the importance of the repository and regulatory role of the endogenous extra cellular matrix in guiding tissue morphogenesis. The microenvironment provided by the endogenous human skin equivalent preserves p63 and K19 positive cells and could finally be involved in: (i) triggering the arrangement of the keratinocytes in follicle-like structures; (ii) promoting the convolute profile of the derma-epidermal junction and (iii) improving epidermis barrier function. We argue that the nature of dermal compartment plays a role in directing epithelial cell fate and function in vitro. PMID- 27267631 TI - Nanoscale effects in dendrimer-mediated targeting of neuroinflammation. AB - Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies. PMID- 27267632 TI - Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis. AB - Pancreatic cancer (PC) is one of the most aggressive malignancies due to intense desmoplasia, extreme hypoxia and inherent chemoresistance. Studies have implicated the expression of chemokine receptor CXCR4 and nuclear receptor co activator-3 (NCOA3) in the development of desmoplasia and metastatic spread of PC. Using a series of polymeric CXCR4 antagonists (PCX), we optimized formulation of PCX/siNCOA3 polyplexes to simultaneously target CXCR4 and NCOA3 in PC. Cholesterol-modified PCX showed maximum CXCR4 antagonism, NCOA3 silencing and inhibition of PC cell migration in vitro. The optimized PCX/siNCOA3 polyplexes were used in evaluating antitumor and antimetastatic activity in orthotopic mouse model of metastatic PC. The polyplexes displayed significant inhibition of primary tumor growth, which was accompanied by a decrease in tumor necrosis and increased tumor perfusion. The polyplexes also showed significant antimetastatic effect and effective suppression of metastasis to distant organs. Overall, dual function PCX/siNCOA3 polyplexes can effectively regulate tumor microenvironment to decrease progression and dissemination of PC. PMID- 27267633 TI - Living alone and depression: the modifying role of the perceived neighborhood environment. AB - OBJECTIVE: Older adults who live alone are more likely to report feelings of depression than those who live with a spouse or other family members. This study examines the effects of residential status and perceived neighborhood characteristics on depression in middle-aged and older adults. METHODS: This study is based on a probability sample of 1049 adults aged 55-98 years (M = 69 years) residing in Allegheny County, Pittsburgh, PA, USA in 2014. Thirty percent of participants reported living alone. We tested a multivariate model using living alone (vs. living with a family member or others) and perceived neighborhood physical and social quality as predictors of depressive symptomatology while controlling for age, sex, race, education, and disability. RESULTS: Living alone (compared to living with a family member) was associated with elevated levels of depressive symptomatology. However, perceptions of neighborhood social quality moderated this association. Living alone was more highly associated with depression when the perceived social quality of the neighborhood was low. Neighborhood social quality was not associated with depression among older adults who lived with a family member. Perceptions of neighborhood physical quality were not significantly associated with depression. CONCLUSIONS: Perceptions of good neighborhood social quality is important for adults who live alone, in terms of fewer symptoms of depression. PMID- 27267634 TI - Perampanel for the treatment of primary generalized tonic-clonic seizures in idiopathic generalized epilepsy. AB - INTRODUCTION: The non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) - receptor antagonist perampanel (PER) was approved in 2015 for treatment of primary generalized tonic-clonic seizures (pGTCS). The aim of this narrative review is to summarize available data on pharmacological properties, efficacy and tolerability of PER in pGTCs. AREAS COVERED: Data sources included MEDLINE, EMBASE, Google Scholar and ClinicalTrials.gov, conference proceedings of the ILAE congresses and the most recent conference proceedings of the American Epilepsy Society (2013 to 2015). EXPERT OPINION: A placebo-controlled clinical phase III study including 164 patients (>= 12 years) with pGTCS in idiopathic generalized epilepsies (IGE) demonstrated efficacy of PER in reducing pGTCS with good tolerability profile, and without aggravating absence seizures or myoclonic seizures. Dizziness, the main adverse event (AE), can be avoided by bedtime administration. Psychiatric AEs ranging from mild depression to aggression and suicidal attempts should be especially monitored in patients with a history of psychiatric disorders. Co-administration of enzyme inducing antiepileptic drugs (AEDs) might decrease PER plasma levels and make dose adjustment necessary. A reduced efficacy of progesterone-containing oral contraceptives should be considered when administering PER to young women. There is lack of evidence on PER treatment in pregnancy. Although no teratogenic effects were observed in animal models, PER is not recommended for women of childbearing age without contraception. PMID- 27267635 TI - Neuropsychiatric manifestations in autoimmune diseases. PMID- 27267636 TI - Sensory disturbance and polyneuropathy in rheumatoid arthritis patients with foot deformity. AB - INTRODUCTION: Our aim in this study was to present the results of sensory evaluation tests and electrophysiological evaluations in rheumatoid arthritis (RA) patients with foot deformity and to determine their relation with general health status and lower extremity functionality. MATERIALS AND METHODS: Fifty-one patients with RA diagnosis and foot deformity were included in the study. Demographic and disease characteristics of the patients were recorded, and a detailed neurological examination was performed. Superficial sensation, pain, heat, vibration, and two-point discrimination sensation were evaluated in each foot, and their sum was used to determine the sensory deficits index (SDI) of 0 10. The presence of polyneuropathy was evaluated with electrophysiological methods. The Health Assessment Questionnaire and mobility and walking subscales of the Arthritis Impact Measurement Scales-2 were used to assess general health status and lower extremity functionality, respectively. According to the sensory examination and electromyography results, patients were compared in terms of their general health status and lower extremity functional status. RESULTS: Sensory disturbance was detected in 39 patients (74%) during the examination; however, 27 patients (52.9%) had polyneuropathy determined electrophysiologically. In patients with sensory deficits, statistically significant deterioration was detected in general health and foot functionality, including mobility and walking, when compared to patients with a normal sensory evaluation. CONCLUSIONS: Even in the presence of normal electrophysiological tests, sensory dysfunction alone seems to be associated with severe disability in general health status and foot functionality when compared to patients with a normal sensory examination. PMID- 27267637 TI - Influence of medical care in the quality of life (WHOQOL-100) of women living with systemic lupus erythematosus. AB - Lupus requires careful treatment by medical specialists. This study aimed to evaluate the quality of life of patients living with Systemic Lupus Erythematosus (SLE). The method approached women with a confirmed diagnosis of SLE under medical supervision in a University hospital outpatient clinic or in a private clinic. We used an instrument containing relevant information of the patient and also the Portuguese version of the World Health Organization Quality of Life Group (WHOQOL-100) questionnaire. The study population consisted of 39 women, married in their majority (56.4%); prevalently aged 37-60 years old; prevalence of diagnosis time over five years (66.7%); and in use of less than 5 medications (69.2%). 92.3% had the disease inactive with higher means in mobility (p=0.0463) and quality of life (p=0.0199) facets; on the other hand, the physical safety and security facet (p=0.0093) showed higher mean for people with active disease. Health and social care analysis showed availability and quality (p=0.0434), even when with other associated diseases (33.3%); and the highest means were Dependence on medicinal substances and medical aids (p=0.0143). The negative results for associated diseases were higher in sexual activity (p=0.0431) and transportation (p=0.0319) facets. IN CONCLUSION: if women living with SLE receive continuous medical attention, they will enjoy good quality of life, while minimizing the complications inherent in this condition. PMID- 27267638 TI - On lupus, vitamin D and leukopenia. AB - BACKGROUND: Immune regulation is among the noncalcemic effects of vitamin D. So, this vitamin may play a role in autoimmune diseases such as systemic lupus erythematosus (SLE). OBJECTIVES: To study the prevalence of vitamin D deficiency in SLE and its association with clinical, serological and treatment profile as well as with disease activity. METHODS: Serum OH vitamin D3 levels were measured in 153 SLE patients and 85 controls. Data on clinical, serological and treatment profile of lupus patients were obtained through chart review. Blood cell count and SLEDAI (SLE disease activity index) were measured simultaneously with vitamin D determination. RESULTS: SLE patients have lower levels of vitamin D than controls (p=0.03). In univariate analysis serum vitamin D was associated with leukopenia (p=0.02), use of cyclophosphamide (p=0.007) and methotrexate (p=0.03). A negative correlation was verified with prednisone dose (p=0.003). No association was found with disease activity measured by SLEDAI (p=0.88). In a multiple regression study only leukopenia remained as an independent association (B=4.04; p=0.02). A negative correlation of serum vitamin level with granulocyte (p=0.01) was also found, but not with lymphocyte count (p=0.33). CONCLUSION: SLE patients have more deficiency of vitamin D than controls. This deficiency is not associated with disease activity but with leucopenia (granulocytopenia). PMID- 27267639 TI - Ozone decreases sperm quality in systemic lupus erythematosus patients. AB - OBJECTIVE: To investigate the deleterious effects of air pollutants exposure in the Sao Paulo metropolitan region on semen quality in systemic lupus erythematosus (SLE). METHODS: A seven-years longitudinal repeated-measures panel study was performed at the Laboratory of Experimental Air Pollution and Rheumatology Division. Two semen samples from 28 post-pubertal SLE patients were analyzed. Daily concentrations of air pollutants exposure: PM10, SO2, NO2, ozone, CO, and meteorological variables were evaluated on 90 days before each semen collection dates using generalized estimating equation models. RESULTS: Intravenous cyclophosphamide (IVCYC) and ozone had an association with a decrease in sperm quality of SLE patients. IVCYC was associated with decreases of 64.3 million of spermatozoa/mL (95% CI 39.01-89.65; p=0.0001) and 149.14 million of spermatozoa/ejaculate (95% CI 81.93-216.38; p=0.017). With regard to ozone, the most relevant adverse effects were observed from lags 80-88, when the exposure to an interquartile range increase in ozone 9-day moving average concentration led to decreases of 22.9 million of spermatozoa/mL (95% CI 5.8-40.0; p=0.009) and 70.5 million of spermatozoa/ejaculate (95% CI 12.3-128.7; p=0.016). Further analysis of 17 patients that never used IVCYC showed association between exposure to ozone (80-88 days) and decrease of 30.0 million of spermatozoa/mL (95% CI 7.0 53.0; p=0.011) and 79.0 million of spermatozoa/ejaculate (95% CI 2.1-155.9; p=0.044). CONCLUSION: Ozone and IVCYC had a consistent adverse effect on semen quality of SLE patients during spermatogenesis. Minimizing exposure to air pollution should be taken into account, especially for patients with chronic systemic inflammatory diseases living in large cities. PMID- 27267640 TI - Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients. AB - OBJECTIVE: The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. METHODS: Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and >=500MUg/L), moderate (<500 and >=100MUg/L) or severe (<100MUg/L). RESULTS: SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. CONCLUSION: This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis. PMID- 27267641 TI - Alcohol, smoking and illicit drug use in pediatric systemic lupus erythematosus patients. AB - OBJECTIVE: To evaluate alcohol, smoking and/or illicit drug use, and history of bullying in adolescent childhood-onset systemic lupus erythematosus and healthy controls. METHODS: 174 adolescents with pediatric rheumatic diseases were selected. All of the 34 childhood-onset systemic lupus erythematosus patients and 35 healthy controls participated in this study. A cross-sectional study included demographic/anthropometric data and puberty markers assessments; structured questionnaire and CRAFFT screening interview. RESULTS: McNemar tests indicated an excellent test-retest reliability of the structured questionnaire (p=1.0). The median current age was similar between childhood-onset systemic lupus erythematosus patients and controls [15 (12-18) vs. 15 (12-18) years, p=0.563]. The median of menarche age was significantly higher in childhood-onset systemic lupus erythematosus patients compared to controls [12 (10-15) vs. 11.5 (9-15) years, p=0.041], particularly in those that lupus had occurred before first menstruation [13 (12-15) vs. 11.5(9-15) years, p=0.007]. The other puberty marker and sexual function parameters were similar in both groups (p>0.05). Alcohol use was similar in both childhood-onset systemic lupus erythematosus patients and controls (38% vs. 46%, p=0.628). A trend of lower frequency of CRAFFT score >=2 (high risk for substance abuse/dependence) was evidenced in childhood-onset systemic lupus erythematosus patients compared to controls (0% vs. 15%, p=0.053). Bullying was reported similarly for the two groups (43% vs. 44%, p=0.950). Further analysis in lupus patients regarding alcohol/smoking/illicit drug use showed no differences in demographic data, puberty markers, history of bullying, sexual function, contraceptive use, disease activity/damage scores, clinical/laboratorial features and treatments (p>0.05). CONCLUSION: This study showed high frequencies of early alcohol use in lupus adolescents and healthy controls, despite of a possible low risk for substance abuse/dependence in childhood-onset systemic lupus erythematosus patients. PMID- 27267642 TI - Hepatitis C virus antibodies in high risk juvenile onset systemic lupus erythematosus. AB - OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in high risk juvenile systemic lupus erythematosus (JSLE). STUDY DESIGN: Forty low income JSLE patients (6M:34F; mean age 19+/-4.4 yrs; mean disease duration 6+/ 3.2 yrs) were studied. Twenty healthy children and adolescents matched for social economical level were included as controls. Anti-HCV tests were performed using a third generation microparticle enzyme immunoassay. Inclusion criterion was low social economical level. RESULTS: The frequencies of anti-HCV antibody were low and comparable between JSLE and control group (2.5% vs. 0, p=1.0). JSLE patients had significantly more risk factors for HCV infection compared to the control group, including immunosuppressive treatment (90% vs. 0, p<0.0001), hospitalization (50% vs. 12.5%, p=0.0006) and invasive procedures (47.5% vs. 12.5%, p=0.001). CONCLUSIONS: The observed low frequency of anti-HCV antibodies in high risk JSLE suggests that this virus does not seem to have a relevant role in the pathogenesis of this disease. PMID- 27267643 TI - Myelopathy in systemic lupus erythematosus: clinical, laboratory, radiological and progression findings in a cohort of 1,193 patients. AB - OBJECTIVE: To describe clinical, laboratory, radiological and progression characteristics of myelopathy in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: A retrospective analysis was performed on a cohort of 1193 patients with SLE (ACR criteria) in order to identify patients with myelopathy (neuropsychiatric ACR). Disease activity was assessed by the SLE activity index (SLEDAI) on the date of the event and functional capacity was assessed by the Expanded Disability Status Scale (EDSS) at the last visit. RESULTS: We identified 14 (1.2%) patients with myelopathy. All were women with a mean age of 30+/-11.5 years. Myelopathy occurred at the diagnosis of SLE in four (28%) patients; and nine (64%) patients had another type of neuropsychiatric manifestation associated. Neurological recurrence was observed in one (7%) patient. Disease activity was observed in 2 (14%) patients. Cerebrospinal fluid presented pleocytosis on 7 (53%) patients; antiphospholipid antibodies were positive in 5 (45%). Magnetic resonance imaging (MRI) showed T2 hyperintensity with a predominance of longitudinal involvement in 6 (86%) patients. Most were treated with intravenous corticosteroids and cyclophosphamide. No patient had full recovery and four (36%) had high EDSS scores. Three (21%) patients died from sepsis early in the course of their myelopathy, during or after immunosuppressive therapy. CONCLUSIONS: Myelopathy occurred in 14 (1.2%) of the patients in our cohort and this may be the first manifestation of the disease occurring independently of systemic disease activity. Although rare, myelopathy shows great morbidity and mortality, can be recurrent and MRI is critical for diagnosis. PMID- 27267645 TI - Prevalence of low back pain in older Brazilians: a systematic review with meta analysis. AB - INTRODUCTION: Prevalence of low back pain (LBP) is expected to increase worldwide with aging of the population but its prevalence in older people is not clear, mainly in developing countries. OBJECTIVE: To estimate the prevalence of LBP in older Brazilians. METHODS: Electronic searches on SciELO, LILACS, MEDLINE, EMBASE and CINAHL, as well as hand-searching identified studies investigating prevalence of LBP in older Brazilians aged 60 years or over. Two independent reviewers selected studies fulfilling the inclusion criteria, assessed risk of bias for each included study and extracted relevant data. Meta-analysis was conducted when enough homogeneity allowed and the GRADE system was used to summarize the overall quality of the evidence. RESULTS: Sixteen studies were included with a total of 28,448 participants. Data from point- and period-prevalence of LBP were obtained. Meta-analysis was conducted for 13 studies reporting point-prevalence. Pooled point-prevalence of LBP was 25.0% (95% CI 18.0-32.0). Other three studies investigated period-prevalence: one-week prevalence=15.0% (95% CI 13.0-18.0); six month prevalence=43.0% (95% CI 42.0-44.0); and 12-month prevalence=13.0% (95% CI 11.0-16.0). Sensitivity analyses were performed for point-prevalence and exclusion of studies with poorer methodological quality tended to increase the estimated prevalence of LBP. CONCLUSION: Moderate-quality evidence showed that at any point in time one in four older Brazilians suffers from LBP. This was the first systematic review investigating nationwide data on the prevalence of LBP in older people and contributes important clinical and epidemiological evidence for policymakers. PMID- 27267644 TI - Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus. AB - OBJECTIVE: To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). METHODS: Patients aged <=18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted. RESULTS: 41 patients with a mean age of 14.5+/-2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%). CONCLUSION: Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment. PMID- 27267646 TI - IgA nephropathy in systemic lupus erythematosus patients: case report and literature review. AB - Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear fine speckled pattern, and anticardiolipin IgM and 280U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non-SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in both the short and long terms. PMID- 27267647 TI - Miliary tuberculosis: a severe opportunistic infection in juvenile systemic lupus erythematosus patients. AB - INTRODUCTION: One of the main issues in juvenile systemic lupus erythematosus (JSLE) patients is infection, such as tuberculosis (TB). Of note, SLE patients are susceptible to pulmonary and extrapulmonary TB. However, to our knowledge, this contagious disease was rarely reported in pediatric lupus population, particularly diffuse or miliary TB. Therefore, from January 1983 to December 2011, 5,635 patients were followed-up at our Pediatric Rheumatology Unit and 285 (5%) of them met the American College of Rheumatology classification criteria for SLE. CASE REPORTS: Four (1.4%) of our JSLE patients had disseminated TB and were described herein. All of them were female gender, received BCG vaccination and did not have a history of TB household contact. The median of current age at TB diagnosis and the period between JSLE and TB diagnosis were 17 years old (range 14-20) and 5.5 years (range 2-7), respectively. All patients developed miliary TB during the course of the disease. The median of SLE Disease Activity Index 2000 (SLEDAI-2K) was 4 (2-16) and the patients were treated with immunosuppressive agents (glucocorticoid, azathioprine and/or intravenous cyclophosphamide). Two of them presented sepsis and TB diagnosis was only established at autopsy, especially with lungs, central nervous system and abdominal involvements. Anti-TB therapy (isoniazid, rifampicin and pyrazinamide) was indicated in the other two TB cases, however they deceased. DISCUSSION: Miliary TB is a rare and severe opportunist infection in pediatric lupus population. This study reinforces the importance of routine searches for TB in JSLE patients. PMID- 27267648 TI - Is there an association between systemic lupus erythematosus and periodontal disease? AB - Periodontal disease results from the interaction between pathogenic bacteria that colonize supragingival and subgingival biofilms and the host, triggering an inflammatory response, with systemic effects leading to immune-mediated destruction of the attachment apparatus and loss of supporting alveolar bone. Immunological pathways and predisposing genetic factors common to periodontal disease and rheumatic diseases, including systemic lupus erythematosus, have been described. Case reports have suggested greater severity of periodontal disease in patients with systemic lupus erythematosus. However, studies evaluating the influence of the treatment of one disease on the clinical and laboratory manifestations of the other have yielded conflicting results. PMID- 27267649 TI - Loading Actinides in Multilayered Structures for Nuclear Waste Treatment: The First Case Study of Uranium Capture with Vanadium Carbide MXene. AB - Efficient nuclear waste treatment and environmental management are important hurdles that need to be overcome if nuclear energy is to become more widely used. Herein, we demonstrate the first case of using two-dimensional (2D) multilayered V2CTx nanosheets prepared by HF etching of V2AlC to remove actinides from aqueous solutions. The V2CTx material is found to be a highly efficient uranium (U(VI)) sorbent, evidenced by a high uptake capacity of 174 mg g(-1), fast sorption kinetics, and desirable selectivity. Fitting of the sorption isotherm indicated that the sorption followed a heterogeneous adsorption model, most probably due to the presence of heterogeneous adsorption sites. Density functional theory calculations, in combination with X-ray absorption fine structure characterizations, suggest that the uranyl ions prefer to coordinate with hydroxyl groups bonded to the V-sites of the nanosheets via forming bidentate inner-sphere complexes. PMID- 27267650 TI - Effect of metal and metal oxide nanoparticles on growth and physiology of globally important food crops: A critical review. AB - The concentrations of engineered metal and metal oxide nanoparticles (NPs) have increased in the environment due to increasing demand of NPs based products. This is causing a major concern for sustainable agriculture. This review presents the effects of NPs on agricultural crops at biochemical, physiological and molecular levels. Numerous studies showed that metal and metal oxide NPs affected the growth, yield and quality of important agricultural crops. The NPs altered mineral nutrition, photosynthesis and caused oxidative stress and induced genotoxicity in crops. The activities of antioxidant enzymes increased at low NPs toxicity while decreased at higher NPs toxicity in crops. Due to exposure of crop plants to NPs, the concentration of NPs increased in different plant parts including fruits and grains which could transfer to the food chain and pose a threat to human health. In conclusion, most of the NPs have both positive and negative effects on crops at physiological, morphological, biochemical and molecular levels. The effects of NPs on crop plants vary greatly with plant species, growth stages, growth conditions, method, dose, and duration of NPs exposure along with other factors. Further research orientation is also discussed in this review article. PMID- 27267651 TI - Decomposition of Iodinated Pharmaceuticals by UV-254 nm-assisted Advanced Oxidation Processes. AB - Iodinated pharmaceuticals, thyroxine (a thyroid hormone) and diatrizoate (an iodinated X-ray contrast medium), are among the most prescribed active pharmaceutical ingredients. Both of them have been reported to potentially disrupt thyroid homeostasis even at very low concentrations. In this study, UV 254 nm-based photolysis and photochemical processes, i.e., UV only, UV/H2O2, and UV/S2O82-, were evaluated for the destruction of these two pharmaceuticals. Approximately 40% of 0.5MUM thyroxine or diatrizoate was degraded through direct photolysis at UV fluence of 160mJcm-2, probably resulting from the photosensitive cleavage of C-I bonds. While the addition of H2O2 only accelerated the degradation efficiency to a low degree, the destruction rates of both chemicals were significantly enhanced in the UV/S2O82- system, suggesting the potential vulnerability of the iodinated chemicals toward UV/S2O82- treatment. Such efficient destruction also occurred in the presence of radical scavengers when biologically treated wastewater samples were used as reaction matrices. The effects of initial oxidant concentrations, solution pH, as well as the presence of natural organic matter (humic acid or fulvic acid) and alkalinity were also investigated in this study. These results provide insights for the removal of iodinated pharmaceuticals in water and/or wastewater using UV-based photochemical processes. PMID- 27267652 TI - PMab-44 Detects Bovine Podoplanin in Immunohistochemistry. AB - Podoplanin (PDPN)/Aggrus is a type I transmembrane O-glycoprotein, which is expressed in several normal tissues including podocytes of kidney and lymphatic endothelial cells. PDPN activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelet; however, only bovine PDPN (bovPDPN) does not possess the platelet-aggregating activity. Although many monoclonal antibodies (mAbs) against human PDPN, mouse PDPN, rat PDPN, and rabbit PDPN have been established, anti-bovPDPN mAbs have not been developed. In this study, we immunized mice with the recombinant proteins of bovPDPN and developed anti bovPDPN mAbs, which are useful in immunohistochemical analysis. One of the clones, PMab-44, is useful for detecting podocytes and lymphatic endothelial cells in normal bovine tissues. PMab-44 also detected bovPDPN specifically in flow cytometry. PMab-44 is expected to be useful for investigating the function of bovPDPN. PMID- 27267653 TI - Communicating printed headings to the ear. AB - Two experiments compared three methods of translating printed headings into an auditory format. In both experiments, college students listened to a text with instructions to stop the recording whenever they heard a heading and type the hierarchical level and exact wording of the heading. Listeners were poor at identifying headings and their levels if the headings were not distinguished from the rest of the text. However, listeners were very good at identifying headings if any method of signalling was used to distinguish headings and communicate their hierarchical level. The methods included: (1) tones preceding headings, (2) changes of speaker to indicate headings or (3) verbal labels preceding headings. Although all three signalling methods improved identification of a heading's hierarchical level, the labelling method was the most effective means of communicating hierarchical level. Thus, the study identifies a simple method of effectively communicating headings in spoken text. Practitioner Summary: The study attempted to identify effective ways of communicating heading information in spoken text. College students listened to texts in order to detect headings and record their wording and hierarchical level. Performance was excellent when headings were preceded by verbal phrases that signalled the upcoming headings and their levels. PMID- 27267654 TI - Internet-based versus Conventional Referral System for Retinopathy of Prematurity Screening in Iran. AB - PURPOSE: To compare the efficacy of an internet-based versus traditional referral system for retinopathy of prematurity (ROP) screening in Iran. METHODS: Two referral screening systems were compared in this prospective observational study. Group A (internet-based) comprised premature babies who were registered into an online system for screening. Their appointments were scheduled automatically based on standardized criteria. Group B (conventional) comprised premature babies whose referrals were based on oral or written recommendations. Babies were referred based on standard criteria (gestational age, GA, <37 weeks or birth weight < 3000 g). RESULTS: A total of 2115 neonates were screened between October 2011 and October 2012. From these 1896 met the inclusion criteria (group A n = 856, group B n = 1040). Time of first examination for neonates with GA<=27 weeks was 30.07+/- 2.72 weeks postmenstrual age in group A and 38.52+/- 7.03 weeks in group B (p = 0.049), and for neonates with GA>27 weeks was 4.86 +/-1.77 and 8.16 +/-4.93 weeks after birth in groups A and B, respectively (p < 0.001). All registered babies in group A attended their first screening exam. One case (0.1%) of advanced ROP developed in group A (in a patient with poor follow-up compliance), whereas advanced stages of ROP were seen in 26 cases (2.5%) in group B (p < 0.001). CONCLUSION: An internet-based registration system for ROP screening resulted in fewer cases of delayed first examination and resulted in fewer babies with advanced ROP. PMID- 27267655 TI - Expression and antimicrobial activity of c-type lysozyme in taimen (Hucho taimen, Pallas). AB - Lysozymes are important defense proteins of the innate immune system and possess high antibacterial activities. In the present study, a full-length c-type lysozyme cDNA (HtLysC) was cloned and characterized from taimen (Hucho taimen, Pallas). The cDNA contains an open reading frame (ORF) of 432 bp encoding 143 amino acid (aa), with 97% identity to LysC of Rainbow trout (Oncorhynchus mykiss). The amino acid sequence possessed a LYZ1 domain (16-140 aa) which contained two conserved residues (Glu 50 and Asp 67), eight conserved cysteine residues and a calcium binding site. RT-PCR analysis showed that HtLysC transcripts were most abundant in liver and less in muscle. The expression of HtLysC was up-regulated in the liver when challenged with Yersinia ruckeri. The recombinant HtLysC (rHtLysC) had lytic activities against Micrococcus lysodeikticus, Aeromonas salmonicida and Y. ruckeri. Enzyme assay showed that the optimal temperature and pH of rHtLysC were 55 degrees C and 6.0, respectively. Taken together, these results indicated that HtLysC might play an important role in innate immune defense against bacterial pathogens as a functional lysozyme. PMID- 27267656 TI - Preparation of Prussian Blue Submicron Particles with a Pore Structure by Two Step Optimization for Na-Ion Battery Cathodes. AB - Traditional Prussian blue (Fe4[Fe(CN)6]3) synthesized by simple rapid precipitation shows poor electrochemical performance because of the presence of vacancies occupied by coordinated water. When the precipitation rate is reduced and polyvinylpyrrolidone K-30 is added as a surface active agent, the as-prepared Prussian blue has fewer vacancies in the crystal structure than in that of traditional Prussian blue. It has a well-defined face-centered-cubic structure, which can provide large channels for Na(+) insertion/extraction. The material, synthesized by slow precipitation, has an initial discharge capacity of 113 mA h g(-1) and maintains 93 mA h g(-1) under a current density of 50 mA g(-1) after 150 charge-discharge cycles. After further optimization by a chemical etching method, the complex nanoporous structure of Prussian blue has a high Brunauer Emmett-Teller surface area and a stable structure to achieve high specific capacity and long cycle life. Surprisingly, the electrode shows an initial discharge capacity of 115 mA h g(-1) and a Coulombic efficiency of approximately 100% with capacity retention of 96% after 150 cycles. Experimental results show that Prussian blue can also be used as a cathode for Na-ion batteries. PMID- 27267657 TI - [Effects of growth hormone treatment on anthropometrics, metabolic risk, and body composition variables in small for gestational age patients]. AB - INTRODUCTION AND OBJECTIVES: Small for gestational age (SGA) children without catch-up growth can benefit from treatment with growth hormone (rhGH). However, they should be monitored very closely because they are at increased risk of metabolic syndrome. MATERIAL AND METHOD: A group of 28 SGA children with a mean age of 8.79 years and undergoing treatment with rhGH were selected for evaluation. Over the course of 4 years, an annual evaluation was performed on the anthropometric variables (weight, height, body mass index [BMI], growth rate, blood pressure and waist perimeter), metabolic risk variables (glycaemia, glycosylated haemoglobin, cholesterol ratio, insulinaemia, insulin-like growth factor 1[IGF1], IGF binding protein-3 [IGFBP-3], IGF1/IGFBP3 ratio, and HOMA index), and body composition variables. RESULTS: Treatment with rhGH was associated with a significant increase in height (-2.76+/-.11 SD to -1.53+/-.17 SD, P=.000), weight (-1.50+/-.09 SD to -1.21+/-.13 SD; P=.016), and growth rate ( 1.43+/-.35 SD to .41+/-.41 SD; P=.009), without a corresponding change in the BMI. Insulinaemia (9.33+/-1.93mU/ml to 16.55+/-1.72mU/ml; P=.044) and the HOMA index (3.63+/-.76 to 6.43+/-.67; P=.042) increased, approaching insulin resistance levels. No changes were observed in the lipid profile. Body composition changes were observed, with a significant increase in lean mass (73.19+/-1.26 to 78.74+/-1.31; P=.037), and a reduction of fat mass (26.81+/-1.26 to 21.26+/-1.31; P=.021). CONCLUSION: Treatment with rhGH is effective for improving anthropometric variables in SGA patients who have not experienced a catch-up growth. It also produces changes in body composition, which may lead to a reduction in risk of metabolic syndrome. However, some insulin resistance was observed. It is important to follow up this patient group in order to find out whether these changes persist into adulthood. PMID- 27267658 TI - Accuracy of Dynamic Navigation for Dental Implant Placement-Model-Based Evaluation. AB - The purpose of this model-based study was to determine the accuracy of placing dental implants using a new dynamic navigation system. This investigation focuses on measurements of overall accuracy for implant placement relative to the virtual plan in both dentate and edentulous models, and provides a comparison with a meta analysis of values reported in the literature for comparable static guidance, dynamic guidance, and freehand placement studies. This study involves 1 surgeon experienced with dynamic navigation placing implants in models under clinical simulation using a dynamic navigation system (X-Guide, X-Nav Technologies, LLC, Lansdale, Pa) based on optical triangulation tracking. Virtual implants were placed into planned sites using the navigation system computer. Post-implant placement cone-beam scans were taken. These scans were mesh overlaid with the virtual plan and used to determine deviations from the virtual plan. The primary outcome variables were platform and angular deviations comparing the actual placement to the virtual plan. The angular accuracy of implants delivered using the tested device was 0.89 degrees +/- 0.35 degrees for dentate case types and 1.26 degrees +/- 0.66 degrees for edentulous case types, measured relative to the preoperative implant plan. Three-dimensional positional accuracy was 0.38 +/- 0.21 mm for dentate and 0.56 +/- 0.17 mm for edentulous, measured from the implant apex. PMID- 27267659 TI - "Not just eliminating the mosquito but draining the swamp": A critical geopolitics of Turkish Monitoring Center for Drugs and Drug Addiction and Turkey's approach to illicit drugs. AB - In the 1970s, Turkey ceased to be a significant producer state of illicit drugs, but it continued to serve as a key route for the trade of drugs between East and West. Over the past decade, however, authorities identified two concerns beyond its continued transit state status. These reported problems entail both new modes of production and a rising incidence of drug abuse within the nation-state - particularly among its youth. Amid these developments, new law enforcement institutions emerged and acquired European sponsorship, leading to the establishment of TUBIM (the Turkish Monitoring Center for Drugs and Drug Addiction). Coordinating with and reporting to the European Union agency EMCDDA (the European Monitoring Center for Drugs and Drug Addiction), TUBIM's primary assigned duties entail the collection and analysis of data on drug abuse, trafficking, and prevention, the geographic identification of sites of concern (e.g. consumption, drug-related crimes, and peoples undergoing treatment), and the production of annual national reports. In this article, we examine the geopolitical origins of TUBIM as Turkey's central apparatus for confronting drug problems and its role as a vehicle for policy development, interpretation, and enforcement. In doing so, we emphasize the political and spatial dimensions inherent to the country's institutional and policy-driven approaches to contend with drug-related problems, and we assess how this line of attack reveals particular ambiguities in mission when evaluated from scales at world regional, national, and local levels. In sum, we assess how Turkey's new institutional and legislative landscapes condition the state's engagements with drug use, matters of user's health, and policy implementation at local scales and amid ongoing political developments. PMID- 27267660 TI - Amyloid beta induces microglia to phagocytose neurons via activation of protein kinase Cs and NADPH oxidase. AB - Alzheimer's disease is characterized by brain plaques of amyloid beta and by neuronal loss, but it is unclear how amyloid beta causes neuronal loss and how to prevent this loss. We have previously shown that amyloid beta causes neuronal loss by inducing microglia to phagocytose neurons, and here we investigated whether protein kinase Cs and NADPH oxidase were involved in this. The loss of neurons induced by amyloid beta in co-cultures of primary glia and neurons was completely prevented by inhibiting protein kinase Cs with Go6976 or Go6983. Directly activating protein kinase Cs with phorbol myristate acetate stimulated microglial phagocytosis, and induced neuronal loss mediated by MFG-E8/vitronectin receptor pathway of microglial phagocytosis. Blocking phagocytosis by MFG-E8 knockout or receptor inhibition left live neurons, indicating microglial phagocytosis was the cause of neuronal death. Phorbol myristate acetate stimulated the microglial NADPH oxidase, and inhibiting the oxidase prevented neuronal loss. A physiological activator of NADPH oxidase, fMLP, also induced neuronal loss dependent on microglia. Amyloid beta-induced neuronal loss was blocked by NADPH oxidase inhibitors, superoxide dismutase or Toll-like receptor function-blocking antibodies. The results indicate that amyloid beta induces microglial phagocytosis of neurons via activating protein kinase Cs and NADPH oxidase, and that activating the kinases or oxidase is sufficient to induce neuronal loss by microglial phagocytosis. Thus inhibiting protein kinase Cs or NADPH oxidase might be beneficial in Alzheimer's disease or other brain pathologies involving inflammatory neuronal loss mediated by microglia. PMID- 27267661 TI - Clinical and prognostic role of matrix metalloproteinase-2, -9 and their inhibitors in breast cancer and liver diseases: A review. AB - Matrix metalloproteinases are a family of zinc endopeptidases with proteolytic activity against the extracellular matrix components. In particular, two members of this family named Gelatinase A and B, as amply documented in the literature, play a key role in the process of tumor growth/metastasis in breast and hepatocellular carcinoma. Their activity is regulated by Tissue Inhibitor of metalloproteinases-1 and -2, which are the physiological inhibitor of Gelatinases A and B respectively. The aim of this review is to determine the current understanding of the clinical and prognostic role of Metalloproteinases-2 and -9 and their inhibitors in the course of breast cancer and liver diseases. Forty-one articles were selected from PubMed by entering the following keywords: liver diseases, breast cancer, MMP-2, TIMP-2; all articles were read and notes were made regarding the number of enrolled patients, pathology, measures, results and these data were used to write this review. Over-expression of both gelatinases is associated with the relapse of disease, metastasis, shorter overall survival in breast cancer and hepatocellular carcinoma and invasion and progression to tumors in chronic liver diseases, and MMPs/TIMPs ratio could be useful in the follow-up of these patients. PMID- 27267663 TI - Exceptional body composition changes attributed to collagen peptide supplementation and resistance training in older sarcopenic men. PMID- 27267662 TI - Axially Chiral Enamides: Substituent Effects, Rotation Barriers, and Implications for their Cyclization Reactions. AB - The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N alkylacetamide derivatives was measured (DeltaG(?) rotation varied between <8.0 and 31.0 kcal mol(-1)). The most important factor in controlling the rate of rotation was the level of alkene substitution, followed by the size of the nitrogen substituent and, finally, the size of the acyl substituent. Tertiary enamides with four alkenyl substituents exhibited half-lives for rotation between 5.5 days and 99 years at 298 K, sufficient to isolate enantiomerically enriched atropisomers. The radical cyclizations of a subset of N-alkenyl-N-benzyl-alpha haloacetamides exhibiting relatively high barriers to rotation round the N alkenyl bond (DeltaG(?) rotation >20 kcal mol(-1)) were studied to determine the regiochemistry of cyclization. Those with high barriers (>27 kcal mol(-1)) did not lead to cyclization, but those with lower values produced highly functionalized gamma-lactams via a 5-endo-trig radical-polar crossover process that was terminated by reduction, an unusual cyclopropanation sequence, or trapping with H2O, depending upon the reaction conditions. Because elevated temperatures were necessary for cyclization, this precluded study of the asymmetric transfer in the reaction of individual atropisomers. However, enantiomerically enriched atropsiomeric enamides should be regarded as potential asymmetric building blocks for reactions that can be accomplished at room temperature. PMID- 27267664 TI - Integrating Well-Being Information and the Multidimensional Adaptive Prediction Process to Estimate Individual-Level Future Health Care Expenditure Levels. AB - Decades of research exist focusing on the utility of self-reported health risk and status data in health care cost predictive models. However, in many of these studies a limited number of self-reported measures were considered. Compounding this issue, prior research evaluated models specified with a single covariate vector and distribution. In this study, the authors incorporate well-being data into the Multidimensional Adaptive Prediction Process (MAPP) and then use a simulation analysis to highlight the value of these findings for future cost mitigation. Data were collected on employees and dependents of a nationally based employer over 36 months beginning in January 2010. The first 2 years of data (2010, 2011) were utilized in model development and selection; 51239 and 54085 members were included in 2010 and 2011, respectively. The final results were based on prospective prediction of 2012 cost levels using 2011 data. The well being-augmented MAPP results showed a 5.7% and 13% improvement in accurate cost capture relative to a reference modeling approach and the first study of MAPP, respectively. The simulation analysis results demonstrated that reduced well being risk across a population can help mitigate the expected upward cost trend. This research advances health care cost predictive modeling by incorporating well being information within MAPP and then leveraging the results in a simulation analysis of well-being improvement. PMID- 27267665 TI - First-Principles Photoemission Spectroscopy of DNA and RNA Nucleobases from Koopmans-Compliant Functionals. AB - The need to interpret ultraviolet photoemission data strongly motivates the refinement of first-principles techniques that are able to accurately predict spectral properties. In this work, we employ Koopmans-compliant functionals, constructed to enforce piecewise linearity in approximate density functionals, to calculate the structural and electronic properties of DNA and RNA nucleobases. Our results show that not only ionization potentials and electron affinities are accurately predicted with mean absolute errors of <0.1 eV, but also that calculated photoemission spectra are in excellent agreement with experimental ultraviolet photoemission spectra. In particular, the role and contribution of different tautomers to the photoemission spectra are highlighted and discussed in detail. The structural properties of nucleobases are also investigated, showing an improved description with respect to local and semilocal density-functional theory. Methodologically, our results further consolidate the role of Koopmans compliant functionals in providing, through orbital-density-dependent potentials, accurate electronic and spectral properties. PMID- 27267666 TI - Reactive Transport Model of Sulfur Cycling as Impacted by Perchlorate and Nitrate Treatments. AB - Microbial souring in oil reservoirs produces toxic, corrosive hydrogen sulfide through microbial sulfate reduction, often accompanying (sea)water flooding during secondary oil recovery. With data from column experiments as constraints, we developed the first reactive-transport model of a new candidate inhibitor, perchlorate, and compared it with the commonly used inhibitor, nitrate. Our model provided a good fit to the data, which suggest that perchlorate is more effective than nitrate on a per mole of inhibitor basis. Critically, we used our model to gain insight into the underlying competing mechanisms controlling the action of each inhibitor. This analysis suggested that competition by heterotrophic perchlorate reducers and direct inhibition by nitrite produced from heterotrophic nitrate reduction were the most important mechanisms for the perchlorate and nitrate treatments, respectively, in the modeled column experiments. This work demonstrates modeling to be a powerful tool for increasing and testing our understanding of reservoir-souring generation, prevention, and remediation processes, allowing us to incorporate insights derived from laboratory experiments into a framework that can potentially be used to assess risk and design optimal treatment schemes. PMID- 27267667 TI - nr0b1 (DAX1) mutation in zebrafish causes female-to-male sex reversal through abnormal gonadal proliferation and differentiation. AB - Sex determinations are diverse in vertebrates. Although many sex-determining genes and pathways are conserved, the mechanistic roles of these genes and pathways in the genetic sex determination are not well understood. DAX1 (encoded by the NR0B1 gene) is a vertebrate specific orphan nuclear receptor that regulates gonadal development and sexual determination. In human, duplication of the NR0B1 gene leads to male-to-female sex reversal. In mice, Nr0b1 shows both pro-testis and anti-testis functions. We generated inheritable nr0b1 mutation in the zebrafish and found the nr0b1 mutation caused homozygous mutants to develop as fertile males due to female-to-male sex reversal. The nr0b1 mutation did not increase Caspase-3 labeling nor tp53 expression in the developing gonads. Introduction of a tp53 mutation into the nr0b1 mutant did not rescue the sex reversal phenotype. Further examination revealed reduction in cell proliferation and abnormal somatic cell differentiation in the nr0b1 mutant gonads at the undifferentiated and bi-potential ovary stages. Together, our results suggest nr0b1 regulates somatic cell differentiation and cell proliferation to ensure normal sex development in the zebrafish. PMID- 27267669 TI - Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts. AB - Orbital fibroblast activation is a central pathologic feature of Graves' Ophthalmopathy (GO). Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been proposed to contribute to GO, but their effects on orbital fibroblasts are largely unknown. We found that bFGF stimulated proliferation and hyaluronan production, but not IL-6 production by orbital fibroblasts, while VEGF hardly affected orbital fibroblast activity. Remarkably, co-stimulation of orbital fibroblasts with bFGF and PDGF-BB synergistically enhanced IL-6 and hyaluronan production and displayed an additive effect on proliferation compared to either bFGF or PDGF-BB stimulation. Nintedanib, a FGF- and PDGF-receptor targeting drug, more efficiently blocked bFGF + PDGF-BB-induced IL-6 and hyaluronan production than dasatinib that only targets PDGF-receptor. In conclusion, bFGF may contribute to orbital inflammation and tissue remodeling in GO, especially through synergistic interaction with PDGF BB. Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. PMID- 27267670 TI - Stage 2 Sleep EEG Sigma Activity and Motor Learning in Childhood ADHD: A Pilot Study. AB - Attention deficit hyperactivity disorder (ADHD) is associated with deficits in motor learning and sleep. In healthy adults, overnight improvements in motor skills are associated with sleep spindle activity in the sleep electroencephalogram (EEG). This association is poorly characterized in children, particularly in pediatric ADHD. Polysomnographic sleep was monitored in 7 children with ADHD and 14 typically developing controls. All children were trained on a validated motor sequence task (MST) in the evening with retesting the following morning. Analyses focused on MST precision (speed-accuracy trade off). NREM Stage 2 sleep EEG power spectral analyses focused on spindle-frequency EEG activity in the sigma (12-15 Hz) band. The ADHD group demonstrated a selective decrease in power within the sigma band. Evening MST precision was lower in ADHD, yet no difference in performance was observed following sleep. Moreover, ADHD status moderated the association between slow sleep spindle activity (12-13.5 Hz) and overnight improvement; spindle-frequency EEG activity was positively associated with performance improvements in children with ADHD but not in controls. These data highlight the importance of sleep in supporting next day behavior in ADHD while indicating that differences in sleep neurophysiology may contribute to deficits in this population. PMID- 27267668 TI - One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health. AB - One carbon metabolism or methyl transfer, a crucial component of metabolism in all cells and tissues, supports the critical function of synthesis of purines, thymidylate and methylation via multiple methyl transferases driven by the ubiquitous methyl donor s-adenosylmethionine. Serine is the primary methyl donor to the one carbon pool. Intracellular folates and methionine metabolism are the critical components of one carbon transfer. Methionine metabolism requires vitamin B12, B6 as cofactors and is modulated by endocrine signals and is responsive to nutrient intake. Perturbations in one carbon transfer can have profound effects on cell proliferation, growth and function. Epidemiological studies in humans and experimental model have established a strong relationship between impaired fetal growth and the immediate and long term consequences to the health of the offspring. It is speculated that during development, maternal environmental and nutrient influences by their effects on one carbon transfer can impact the health of the mother, impair growth and reprogram metabolism of the fetus, and cause long term morbidity in the offspring. The potential for such effects is underscored by the unique responses in methionine metabolism in the human mother during pregnancy, the absence of transsulfuration activity in the fetus, ontogeny of methionine metabolism in the placenta and the unique metabolism of serine and glycine in the fetus. Dietary protein restriction in animals and marginal protein intake in humans causes characteristic changes in one carbon metabolism. The impact of perturbations in one carbon metabolism on the health of the mother during pregnancy, on fetal growth and the neonate are discussed and their possible mechanism explored. PMID- 27267671 TI - p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein Protein Interactions. AB - The AAA+ ATPase p97/VCP adopts at least three conformations that depend on the binding of ADP and ATP and alter the orientation of the N-terminal protein protein interaction (PPI) domain into "up" and "down" conformations. Point mutations that cause multisystem proteinopathy 1 (MSP1) are found at the interface of the N domain and D1-ATPase domain and potentially alter the conformational preferences of p97. Additionally, binding of "adaptor" proteins to the N-domain regulates p97's catalytic activity. We propose that p97/adaptor PPIs are coupled to p97 conformational states. We evaluated the binding of nucleotides and the adaptor proteins p37 and p47 to wild-type p97 and MSP1 mutants. Notably, p47 and p37 bind 8-fold more weakly to the ADP-bound conformation of wild-type p97 compared to the ATP-bound conformation. However, MSP1 mutants lose this nucleotide-induced conformational coupling because they destabilize the ADP bound, "down" conformation of the N-domain. Loss in conformation coupling to PPIs could contribute to the mechanism of MSP1. PMID- 27267672 TI - Two new sesquiterpenes from the aerial parts of Schizonepeta tenuifolia. AB - Two new sesquiterpenes named petafolias A-B were isolated from the aerial parts of Schizonepeta tenuifolia. Their structures were elucidated by various spectroscopic techniques (UV, IR, MS, CD, 1D, and 2D NMR). PMID- 27267673 TI - Seeing Blue As Red: A Hypnotic Suggestion Can Alter Visual Awareness of Colors. AB - Some highly hypnotizable individuals have reported changes in objects' color with suggestions given in normal waking state. However, it is not clear whether this occurs only in their imagination. The authors show that, although subjects could imagine colors, a posthypnotic suggestion was necessary for seeing altered colors, even for a hypnotic virtuoso. She reported posthypnotic color alterations also selectively in response to specific target shapes in briefly presented object arrays. Surprisingly, another highly hypnotizable person showed a very different pattern of results. The control participants could not simulate virtuosos' results by applying cognitive strategies. The results imply that hypnosis can alter the functioning of automatic visual processes but only in some of the most hypnotizable individuals. PMID- 27267674 TI - The Elkins Hypnotizability Scale: Assessment of Reliability and Validity. AB - Measuring hypnotizability is an integral part of hypnosis research and is also relevant for predicting effectiveness of hypnosis-based therapies. The Elkins Hypnotizability Scale (EHS) was designed to meet the needs of modern hypnosis research and clinical practice. Reliability, validity, and normative data were explored by subjecting 230 participants to the EHS and Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C). The EHS demonstrated adequate internal consistency (alpha = .78), its items showed good discriminating ability, and scores of the two scales were highly correlated (rho = .86). Results indicate that the EHS is a reliable and valid tool to assess hypnotizability. Further research is needed to establish its role as a surrogate for the SHSS:C. PMID- 27267675 TI - Asymmetric Tactile Foot Stimulation: How Postural Studies May Suggest New Views of Hypnotizability. AB - Earlier studies have shown hypnotizability-related postural effects of visual suppression and of leg and neck proprioceptive alteration. This study completes this investigation by demonstrating the postural effects of asymmetric tactile foot stimulation in standing participants with different hypnotizability scores. During this stimulation, body sway changed in medium-to-high more than in low-to medium hypnotizable participants. Findings support the view that high hypnotizability is associated with higher vulnerability of posture to sensory alteration; together with earlier results, they suggest a role of the cerebellum in the observed hypnotizability-related differences and prompt investigation of cerebral structures and factors potentially responsible for both the cognitive and physiological aspects of hypnotizability. PMID- 27267676 TI - Complementing the Latest APA Definition of Hypnosis: Sensory-Motor and Vascular Peculiarities Involved in Hypnotizability. AB - The aim of this article is to complement the recently revised American Psychological Association (APA) definition of hypnotizability. It (a) lists a few differences in sensorimotor integration between subjects with high (highs) and low (lows) hypnotizability scores in the ordinary state of consciousness and in the absence of suggestions, (b) proposes that hypnotizability-related cerebellar peculiarities may account for them, PMID- 27267677 TI - Attentional Dissociation in Hypnosis And Neural Connectivity: Preliminary Evidence from Bilateral Electrodermal Activity. AB - According to recent findings, interhemispheric interactions and information connectivity represent crucial mechanisms used in processing information across various sensory modalities. To study these interactions, the authors measured bilateral electrodermal activity (EDA) in 33 psychiatric outpatients. The results show that, during congruent Stroop stimuli in hypnosis, the patients with higher hypnotizability manifest a decreased level of interhemispheric information transfer measured by pointwise transinformation (PTI) that was calculated from left and right EDA records. These results show that specific shifts of attentional focus during hypnosis are related to changes of interhemispheric interactions that may be reflected in neural connectivity calculated from the bilateral EDA measurement. This attentional shift may cause dissociated attentional control disturbing integrative functions of consciousness and contextual experiences. PMID- 27267678 TI - From the Influence of Traumas to Therapeutic Letting Go: The Contribution of Hypnosis and EMDR. AB - The development of new psychotherapies such as Eye Movement Desensitization and Reprocessing (EDMR) has led to numerous fresh approaches to both the treatment of trauma and to the understanding of underlying psychopathology. A unified view appears to be slowly emerging in an attempt to corroborate clinical practice with neurobiological data. This article attempts to demonstrate links between alternate psychotherapies by highlighting what appears to be an invariant among these approaches, namely "letting go." This concept refers to a psycho-physical dynamic that combines psychological dissociation and reassociation, as well as the body's vagotonic mechanisms. Following an explanation of this process, it is demonstrated how letting go can manifest itself physiologically and why this may be significant in the study of trauma. PMID- 27267680 TI - In Memoriam: Graham Dene Burrows, 1938-2016. PMID- 27267679 TI - An Evaluation of the Effect of Hypnosis on Postoperative Analgesia following Laparoscopic Cholecystectomy. AB - Little attention has been paid to the effectiveness of hypnosis in improving the results of surgery in Iran. One hundred and twenty patients scheduled for laparoscopic cholecystectomy were randomly divided into either control (standard care) or experimental (hypnosis) groups. Prior to surgery and again after surgery, abdominal pain, nausea, and vomiting were assessed. The results suggest that hypnosis could effectively reduce pain after laparoscopic cholecystectomy and significantly reduce hospitalization time. PMID- 27267681 TI - Corrigendum. PMID- 27267683 TI - Erratum to: "What They Want: Inclusion of Blood and Marrow Transplantation Survivor Preference in the Development of Models of Care for Long-Term Health in Sydney, Australia" [Biol Blood Marrow Transplant 2016;22:731-743]. PMID- 27267684 TI - Repeated ventral midbrain neurotensin injections sensitize to amphetamine-induced locomotion and ERK activation: A role for NMDA receptors. AB - Previous studies have shown that activation of ventral midbrain NMDA receptors is required to initiate sensitization by amphetamine. In view of the recent evidence that neurotensin modulates ventral midbrain glutamate neurotransmission, we tested the hypothesis that neurotensin is acting upstream to glutamate to initiate sensitization to the behavioral and neurochemical effects of amphetamine. During a first testing phase, adult male rats implanted with bilateral ventral midbrain cannulae were injected every second day for three days with D-[Tyr11]neurotensin (1.5 nmol/side), the preferred NMDA GluN2A/B antagonist, CPP (40 or 120 pmol/side), the selective GluN2B antagonist, Ro04-5595 (200 or 1200 pmol/side), CPP (40 or 120 pmol/side) + D-[Tyr11]neurotensin (1.5 nmol/side) or Ro04-5595 (200 or 1200 pmol/side) + D-[Tyr11]neurotensin (1.5 nmol/side) and locomotor activity was measured immediately after the injection. Five days after the last central injection, the locomotor response or the expression of phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) in neurons of different limbic nuclei was measured following a systemic injection of amphetamine sulfate (0.75 mg/kg, i.p.). Results show that amphetamine induced significantly stronger locomotor activity and pERK1/2 expression in the nucleus accumbens shell and infralimbic cortex in neurotensin pre-exposed animals than in controls (vehicle pre-exposed). These sensitization effects initiated by neurotensin were prevented by CPP, but not Ro04-5595. These results support the hypothesis that neurotensin is stimulating glutamate neurotransmission to initiate neural changes that sub-serve amphetamine sensitization and that glutamate is acting on NMDA receptors that are mostly likely composed of GluN2A, but not GluN2B, subunits. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. PMID- 27267685 TI - Metabotropic glutamate receptor, mGlu5, mediates enhancements of hippocampal long term potentiation after environmental enrichment in young and old mice. AB - The metabotropic glutamate (mGlu) receptor, mGlu5, is of particular relevance for hippocampal function. It is critically required for the expression of long-term potentiation (LTP) and long-term depression (LTD), regulates neuronal oscillations, maintains the stability of place fields and is required for hippocampus-dependent memory. MGlu5-dysfunctions are associated with profound cognitive deficits in humans, and mGlu5 has been targeted as a putative cognitive enhancer. Cognitive enhancement, by means of environmental enrichment (EE) in rodents, results in improved hippocampal synaptic plasticity and memory. Here, we explored whether mGlu5 contributes to these enhancements. MGlu5-antagonism dose dependently impaired the early phase of LTP (>4 h) in the CA1 region of young(3-4 month old) mice. Late-LTP (>24 h) was also impaired. LTP (>24 h) elicited in old (10-14 month old) mice displayed reduced sensitivity to mGlu5 antagonism. Short term potentiation (STP, < 2 h) that was elicited by weaker afferent stimulation was unaffected by mGlu5-antagonism in both age-groups. EE significantly amplified STP (<2 h) in old and young animals, but did not increase the duration of synaptic potentiation, or promote induction of LTP. The improvement in STP was prevented by mGlu5-antagonism, in both young and old animals. These results indicate that modifications of the synapse that underlie improvements of LTP by EE require the contribution of mGlu5. Strikingly, although LTP in old mice does not critically depend on mGlu5, improvements in synaptic potentiation resulting from EE are mGlu5-dependent in old mice. Regarded in light of the known role for mGlu5 in hippocampal function and pathophysiology, these data suggest that mGlu5 regulation of synaptic information storage is pivotal to optimal hippocampal function. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. PMID- 27267686 TI - High fat diet augments amphetamine sensitization in mice: Role of feeding pattern, obesity, and dopamine terminal changes. AB - High fat (HF) diet-induced obesity has been shown to augment behavioral responses to psychostimulants that target the dopamine system. The purpose of this study was to characterize dopamine terminal changes induced by a HF diet that correspond with enhanced locomotor sensitization to amphetamine. C57BL/6J mice had limited (2hr 3 d/week) or extended (24 h 7 d/week) access to a HF diet or standard chow for six weeks. Mice were then repeatedly exposed to amphetamine (AMPH), and their locomotor responses to an amphetamine challenge were measured. Fast scan cyclic voltammetry was used to identify changes in dopamine terminal function after AMPH exposure. Exposure to a HF diet reduced dopamine uptake and increased locomotor responses to acute, high-dose AMPH administration compared to chow fed mice. Microdialysis showed elevated extracellular dopamine in the nucleus accumbens (NAc) coincided with enhanced locomotion after acute AMPH in HF fed mice. All mice exhibited locomotor sensitization to amphetamine, but both extended and limited access to a HF diet augmented this response. Neither HF-fed group showed the robust amphetamine sensitization-induced increases in dopamine release, reuptake, and amphetamine potency observed in chow fed animals. However, the potency of amphetamine as an uptake inhibitor was significantly elevated after sensitization in mice with extended (but not limited) access to HF. Conversely, after amphetamine sensitization, mice with limited (but not extended) access to HF displayed reduced autoreceptor sensitivity to the D2/D3 agonist quinpirole. Additionally, we observed reduced membrane dopamine transporter (DAT) levels after HF, and a shift in DAT localization to the cytosol was detected with limited access to HF. This study showed that different patterns of HF exposure produced distinct dopamine terminal adaptations to repeated AMPH, which differed from chow fed mice, and enhanced sensitization to AMPH. Locomotor sensitization in chow fed mice coincided with elevated DAT function and increased AMPH potency; however, the enhanced behavioral response to AMPH after HF exposure was unique in that it coincided with reduced DAT function and diet pattern-specific adaptations. PMID- 27267687 TI - Evaluating the neurotherapeutic potential of a water-soluble progesterone analog after traumatic brain injury in rats. AB - The poor aqueous solubility of progesterone (PROG) limits its potential use as a therapeutic agent. We designed and tested EIDD-1723, a novel water-soluble analog of PROG with >100-fold higher solubility than that of native PROG, as candidate for development as a field-ready treatment for traumatic brain injury (TBI). The pharmacokinetic effects of EIDD-1723 on morphological and functional outcomes in rats with bilateral cortical impact injury were evaluated. Following TBI, 10 mg/kg doses of EIDD-1723 or PROG were given intramuscularly (i.m.) at 1, 6 and 24 h post-injury, then daily for the next 6 days, with tapering of the last 2 treatments. Rats were tested pre-injury to establish baseline performance on grip strength and sensory neglect, and then retested at 4, 9 and 21 days post-TBI. Spatial learning was evaluated from days 11-17 post-TBI. At 22 days post-injury, rats were perfused and brains extracted and processed for lesion size. For the edema assay the animals were killed and brains removed at 24 h post-injury. EIDD 1723 significantly reduced cerebral edema and improved recovery from motor, sensory and spatial learning deficits as well as, or better than, native PROG. Pharmacokinetic investigation after a single i.m. injection in rats revealed that EIDD-1723 was rapidly converted to the active metabolite EIDD-036, demonstrating first-order elimination kinetics and ability to cross the blood-brain barrier. Our results suggest that EIDD-1723 represents a substantial advantage over current PROG formulations because it overcomes storage, formulation and delivery limitations of PROG and can thereby reduce the time between injury and treatment. PMID- 27267689 TI - Antioxidant-rich beetroot juice does not adversely affect acute neuromuscular adaptation following eccentric exercise. AB - This study examined the effects of beetroot juice on the repeated bout effect (RBE) to eccentric exercise. Twenty-nine recreationally active males performed two bouts of 100-drop jumps, separated by 14-21 days. Using a double-blind, independent groups design, participants consumed either a higher dose beetroot juice (H-BT; 250 ml, n = 10), a lower dose beetroot juice (L-BT; 125 ml, n = 9) or an isocaloric placebo (PLA; 250 ml, n = 10) for 3 days after bout 1; no drinks were consumed after bout 2. Maximal isometric voluntary contraction (MIVC), countermovement jump (CMJ), pressure-pain threshold (PPT) and creatine kinase (CK) were measured pre, post, 24, 48 and 72 h following both bouts. In bout 2, CMJ and MIVC recovered quicker and CK activity was attenuated (versus bout 1) (P < 0.05) in all groups, demonstrating an RBE. At 24 h post bout 1, MIVC was 84.1 +/- 16.1, 83.6 +/- 11.6, 79.7 +/- 15.1% relative to baseline values in the H-BT, L-BT and PLA groups, respectively; at 24 h post bout 2, MIVC recovered to 90.7 +/ 13.7, 92.9 +/- 6.9, 87.8 +/- 6.9, in the H-BT, L-BT and PLA groups, respectively. These findings suggest that supplementation with antioxidant-rich beetroot juice does not adversely affect acute adaptations to a bout of eccentric exercise. PMID- 27267690 TI - Enhanced visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid over ZnIn2S4/g-C3N4 photocatalyst. AB - ZnIn2S4/g-C3N4 heterojunction photocatalyst was successfully synthesized via a simple hydrothermal method and applied to visible-light photocatalytic decomposition of 2,4-dichlorophenoxyacetic acid (2,4-D) from aqueous phase. The flower-like ZnIn2S4 particles were dispersed on the surface of g-C3N4 nanosheets in the ZnIn2S4/g-C3N4 composite. The composite showed higher separation rate of electron-hole pairs as compared to ZnIn2S4 and g-C3N4. Consequently, the ZnIn2S4/g-C3N4 composite exhibited enhanced visible light photocatalytic decomposition efficiency of 2,4-D, within 20% ZnIn2S4/g-C3N4 composite owning the highest photocatalytic efficiency and initial rate. The initial rates of 2,4-D degradation on g-C3N4, ZnIn2S4, and 20% ZnIn2S4/g-C3N4 were 1.23, 0.57 and 3.69mmol/(gcath), respectively. The h(+) and O2(-) were found to be the dominant active species for 2,4-D decomposition. The photocatalytic degradation pathways of 2,4-D by ZnIn2S4/g-C3N4 under visible light irradiation were explored. The ZnIn2S4/g-C3N4 composite displayed high photostability in recycling tests, reflecting its promising potential as an effective visible light photocatalyst for 2,4-D treatment. PMID- 27267691 TI - Pyrosequencing analysis of bacterial diversity in soils contaminated long-term with PAHs and heavy metals: Implications to bioremediation. AB - Diversity, distribution and composition of bacterial community of soils contaminated long-term with both polycyclic aromatic hydrocarbons (PAHs) and heavy metals were explored for the first time following 454 pyrosequencing. Strikingly, the complete picture of the Gram positive (+ve) and Gram negative ( ve) bacterial profile obtained in our study illustrates novel postulates that include: (1) Metal-tolerant and PAH-degrading Gram -ves belonging to the class Alphaproteobacteria persist relatively more in the real contaminated sites compared to Gram +ves, (2) Gram +ves are not always resistant to heavy metal toxicity, (3) Stenotrophomonas followed by Burkholderia and Pseudomonas are the dominant genera of PAH degraders with high metabolic activity in long-term contaminated soils, (4) Actinobacteria is the predominant group among the Gram +ves in soils contaminated with high molecular weight PAHs that co-exist with toxic heavy metals like Pb, Cu and Zn, (5) Microbial communities are nutrient driven in natural environments and (6) Catabolically potential Gram +/-ves with diverse applicability to remediate the real contaminated sites evolve eventually in the historically-polluted soils. Thus, the most promising indigenous Gram +/ ve strains from the long-term contaminated sites with increased catabolic potential, enzymatic activity and metal tolerance need to be harnessed for mixed contaminant cleanups. PMID- 27267688 TI - Adeno-Associated Virus-Based Gene Therapy for CNS Diseases. AB - Gene therapy is at the cusp of a revolution for treating a large spectrum of CNS disorders by providing a durable therapeutic protein via a single administration. Adeno-associated virus (AAV)-mediated gene transfer is of particular interest as a therapeutic tool because of its safety profile and efficiency in transducing a wide range of cell types. The purpose of this review is to describe the most notable advancements in preclinical and clinical research on AAV-based CNS gene therapy and to discuss prospects for future development based on a new generation of vectors and delivery. PMID- 27267692 TI - Source apportionment of mass concentration and inhalation risk with long-term ambient PCDD/Fs measurements in an urban area. AB - This study applies a receptor model to quantify source contributions to ambient concentration of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and inhalation cancer risk in Taipei from 2003 through 2009. Seventeen PCDD/F congeners were used in the effective variance solution to the Chemical Mass Balance equations to estimate source-specific mass contributions and inhalation risks. The average total PCDD/F concentration was 0.611pg/Nm(3) (0.036pg I TEQ/Nm(3)). Traffic emissions contributed the most to the PCDD/F concentration (55.7%), followed by waste incinerators (18.6%) and joss stick burning (9.6%). For the inhalation cancer risk, the average was 1.1*10(-6) with traffic, waste incinerators, and joss paper burning as the main contributors (67.3%, 19.4%, and 6.3%, respectively). The mass and risk contributions of waste incinerators decreased significantly from 2003 to 2009 and were higher at downwind sites than at upwind sites. Reducing PCDD/F emissions from traffic and waste incinerators would provide the greatest health benefit. Policies that reduce the uncontrolled burning of joss stick and joss paper also need to be implemented. PMID- 27267693 TI - Analysis of a gas-liquid film plasma reactor for organic compound oxidation. AB - A pulsed electrical discharge plasma formed in a tubular reactor with flowing argon carrier gas and a liquid water film was analyzed using methylene blue as a liquid phase hydroxyl radical scavenger and simultaneous measurements of hydrogen peroxide formation. The effects of liquid flow rate, liquid conductivity, concentration of dye, and the addition of ferrous ion on dye decoloration and degradation were determined. Higher liquid flow rates and concentrations of dye resulted in less decoloration percentages and hydrogen peroxide formation due to initial liquid conductivity effects and lower residence times in the reactor. The highest decoloration energy yield of dye found in these studies was 5.2g/kWh when using the higher liquid flow rate and adding the catalyst. The non-homogeneous nature of the plasma discharge favors the production of hydrogen peroxide in the plasma-liquid interface over the chemical oxidation of the organic in the bulk liquid phase and post-plasma reactions with the Fenton catalyst lead to complete utilization of the plasma-formed hydrogen peroxide. PMID- 27267694 TI - Serum soluble interleukin-2 receptor level at diagnosis predicts transformation in patients with follicular lymphoma. AB - We evaluated 121 patients with follicular lymphoma (FL) and analyzed the association between the soluble interleukin-2 receptor (sIL-2R) level at diagnosis and the cumulative incidence of transformation. By a receiver-operating characteristic analysis, we determined a cutoff value of sIL-2R for transformation at 4360 U/mL to classify patients into two groups. Patients in the high sIL-2R group showed a shorter progression-free survival (PFS) and shorter disease-specific survival (DSS) (p < 0.001 and p = 0.018). Furthermore, the cumulative incidence of transformation in the high sIL-2R group was higher than that in the low sIL-2R group (40.9% vs. 7.3% at 5 years, p < 0.001). In a multivariate analysis, high sIL-2R was an independent predictive risk factor for transformation (HR 7.42, 95% CI: 2.75-20.0, p < 0.001). This study showed that the sIL-2R level at diagnosis may be a prognostic factor for transformation, PFS, and DSS in patients with FL. PMID- 27267695 TI - Altered intrinsic regional brain activity in female asthmatics with or without depressive symptoms: A resting-state functional magnetic resonance imaging study. AB - BACKGROUND: Previous studies have suggested that asthma patients are more susceptible to anxiety or depression and have more specifically elevated depressive symptomology. These psychological factors are associated with anatomical brain changes. However, little is known about alterations in spontaneous brain activity in asthma patients with depressive symptoms. Here we hypothesized that asthma patients exhibit an altered regional spontaneous brain activity, which may contribute to their increased susceptibility to depression and poor perception of asthma symptoms. The purpose of this study was to examine spontaneous brain activity in female asthma patients using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Eleven asthmatics without depressive symptoms (ASs), 14 asthmatics with depressive symptoms (ADs), and 15 age- and education-matched healthy controls (HCs) completed rs-fMRI. The regional homogeneity (ReHo) value was calculated based on rs-fMRI to assess local signal synchrony strength and compared among the groups. Correlation analyses were conducted between both ReHo values and clinical parameters. RESULT: Compared with HCs, ASs showed a significantly increased ReHo in the right insula; whereas ADs showed a significantly decreased ReHo in the right insula, which positively correlated with nocturnal symptom score in the Asthma Control Test (r = 0.562, P = 0.036). No significant correlation was observed between the total ACT scores and right insula activities (r = 0.263, P = 0.364). CONCLUSION: Decreased ReHo in the right insula may play an important role in depressive symptoms and abnormal asthma symptom perception. PMID- 27267696 TI - Perinatal outcome of macrosomic infants born to diabetic versus non-diabetic mothers. AB - OBJECTIVE: To assess the incidence and perinatal complications of macrosomic infants born to diabetic and non-diabetic mothers. PATIENTS AND METHODS: A six year retrospective study of newborns at our hospital. A total of 996 macrosomic newborns were found. Maternal characteristics, mode of delivery, and perinatal outcomes were studied. RESULTS: Of 18005 newborns, 996 were macrosomic infants (5.53%). Of these, 103 (10.3%) were born to diabetic mothers. Diabetic mothers had higher parity (1.89 vs. 1.35; P<0.000), cesarean section rate (52.4 vs. 31.1%; P<0.05), and resuscitation rate (5.8 vs. 1.8%; P<0.006; RR: 2.9; 95% CI: 1.42-5.9), and greater need for hospitalization (19.4 vs. 9.6%; p<0.002; RR: 2; 95% CI: 1.3-3.2) and intensive care (5.8 vs. 0.7%; P<0.000; RR: 5.3; 95% CI: 2.8 10) mostly for hypoglycemia (7.8 vs. 1%; P<0.000; RR: 5; 95% CI: 2.8-8.3), jaundice (8.7 vs. 2.1%; P<0.000; RR: 3.1; 95% CI: 1.9-5.9), respiratory distress (4.9 vs. 1.3%; P<0.009; RR: 2.9; 95% CI: 1.4-6.7), and asphyxia (2.9 vs. 0.4%; P<0.005; RR: 4.3; 95% CI: 1.8-11.1). No differences were found in birth trauma. CONCLUSIONS: Macrosomic infants born to diabetic mothers have an increased risk of hospital admission in the neonatal period for hypoglycemia, jaundice, respiratory distress, and asphyxia, and a greater need of intensive care. Obstetric trauma rates were similar in both groups. PMID- 27267698 TI - Natural Products as a Source for Novel Antibiotics. AB - Natural products have historically been of crucial importance in the identification and development of antibacterial agents. Interest in these systems has waned in recent years, but the rapid emergence of resistant bacterial strains has forced their re-evaluation as a route to identify novel chemical skeletons with antibacterial activity for elaboration in drug development. This overview examines the current situation, highlights new natural product systems which have been found, together with re-examination of some old ones, and new technologies for their identification. While natural products certainly have the potential to re-emerge as a key start-point in antibacterial drug discovery, reports of new or reinvestigated structures need to be supported with sufficient quality chemical (solubility, stability), biochemical (including toxicity in particular, along with target information) and microbiological [minimum inhibitory concentration (MIC) and resistance frequency] validation data to assist in the identification of promising hit structures and to avoid wasted effort from trawling over already cultivated territory. This is particularly important in a resource-limited research environment. PMID- 27267697 TI - Recent Structural Insights into Cytochrome P450 Function. AB - Cytochrome P450 (P450) enzymes are important in the metabolism of drugs, steroids, fat-soluble vitamins, carcinogens, pesticides, and many other types of chemicals. Their catalytic activities are important issues in areas such as drug drug interactions and endocrine function. During the past 30 years, structures of P450s have been very helpful in understanding function, particularly the mammalian P450 structures available in the past 15 years. We review recent activity in this area, focusing on the past 2 years (2014-2015). Structural work with microbial P450s includes studies related to the biosynthesis of natural products and the use of parasitic and fungal P450 structures as targets for drug discovery. Studies on mammalian P450s include the utilization of information about 'drug-metabolizing' P450s to improve drug development and also to understand the molecular bases of endocrine dysfunction. PMID- 27267700 TI - Tuning the Selectivity of Dendron Micelles Through Variations of the Poly(ethylene glycol) Corona. AB - Engineering controllable cellular interactions into nanoscale drug delivery systems is key to enable their full potential. Here, using folic acid (FA) as a model targeting ligand and dendron micelles (DM) as a nanoparticle (NP) platform, we present a comprehensive experimental and modeling investigation of the structural properties of DMs that govern the formation of controllable, FA mediated cellular interactions. Our experimental results demonstrate that a high level of control over the specific cell interactions of FA-targeted DMs can be achieved through modulation of the PEG corona length and the FA content. Using various molecular weight PEGs (0.6K, 1K, and 2K g/mol) and contents of dendron-FA conjugate incorporated into DMs (0, 5, 10, 25 wt %), the cell interactions of the targeted DMs could be controlled to exhibit minimal to >25-fold enhancement over nontargeted DMs. Molecular dynamics simulations indicated that structural characteristics, such as solvent accessible surface area of FA, local PEG density near FA, and FA mobility, account in part for the experimental differences in cellular interactions. The molecular structure that allows FA to depart from the surface of DMs to facilitate the initial cell surface binding was revealed to be the most important contributor for determining FA-mediated cellular interactions of DMs. The modular properties of DMs in controlling their specific cell interactions support the potential of DMs as a delivery platform and offer design cues for future development of targeted NPs. PMID- 27267701 TI - Arsenite accumulation in the mouse eye. AB - Elevated arsenic (As) concentrations in drinking water are a major worldwide public health concern. Exposure to As is associated with carcinogenesis, skin lesions, cardiovascular disease, cognitive deficits, and other disorders. However, little is known regarding chronic As-mediated effects on the eye. Oxidative stress is believed to be an important factor in As-related pathology and is also implicated in certain eye diseases such as cataract. Thus, elevated exposure to arsenic could potentially be a contributing factor for ocular pathology. A pilot study was therefore initiated to determine whether As could be detected in eye tissue of mice exposed to sodium arsenite in drinking water. Total As concentrations were determined by inductively coupled plasma-mass spectroscopy in whole eyes, lens, liver, heart, lung, kidneys, spleen, brain, and hair from mice given 0, 10, 50, or 250 ppm sodium arsenite in their drinking water for 4 wk or 0, 10 or 50 ppm for 6 mo. Dose-dependent increases in As concentration were observed in all organs and tissues. Surprisingly, As concentrations in the eye and lens were significantly higher than those in liver, lung, heart, spleen, and brain and similar to that found in kidneys. The relatively high concentration in the eye, and the lens in particular, suggests As exposure may be a contributing factor in cataract formation in parts of the world where As in drinking water is endemic. PMID- 27267702 TI - Effect of genetic strain and gender on age-related changes in body composition of the laboratory rat. AB - Body fat serves as a storage compartment for lipophilic pollutants and affects the pharmacokinetics of many toxic chemicals. Understanding how body fat varies with gender, strain, and age may be essential for development of experimental models to study mechanisms of toxicity. Nuclear magnetic resonance (NMR)-based analysis serves as a noninvasive means of assessing proportions of fat, lean, and fluid in rodents over their lifetime. The aim of this study was to track changes in body composition of male and female Long-Evans (LE), Sprague-Dawley (SD), Fischer (F334), and Brown Norway (BN) rats from postweaning over a >2-yr period. Percent fat of preweaned LE and SD rats was markedly higher compared to the other strains. LE and SD strains displayed marked increases in body fat from weaning to 8 mo of age. Postweaned F344 male and females showed relatively low levels of percent fat; however, at 2 yr of age percent fat of females was equal to that of SD and LE in females. BN rats showed the highest levels of lean tissue and lowest levels of fat. Percent fat of the BN strain rose at the slowest rate as they aged. Percent fluid was consistently higher in males for all strains. Females tended to have higher percent fat than males in LE, SD, and F344 strains. Assessing changes in body fat as well as lean and fluid of various strains of male and female rats over their lifetime may prove useful in many research endeavors, including pharmacokinetics of lipophilic toxicants, mechanisms underlying obesity, and metabolic disorders. PMID- 27267699 TI - Systematic Targeting of Protein-Protein Interactions. AB - Over the past decade, protein-protein interactions (PPIs) have gone from being neglected as 'undruggable' to being considered attractive targets for the development of therapeutics. Recent advances in computational analysis, fragment based screening, and molecular design have revealed promising strategies to address the basic molecular recognition challenge: how to target large protein surfaces with specificity. Several systematic and complementary workflows have been developed to yield successful inhibitors of PPIs. Here we review the major contemporary approaches utilized for the discovery of inhibitors and focus on a structure-based workflow, from the selection of a biological target to design. PMID- 27267703 TI - Does a methionine-to-norleucine substitution in PGLa influence peptide-membrane interactions? AB - Yes. To understand the molecular mechanisms of amphiphilic membrane-active peptides, it is essential to study their interactions with lipid bilayers under near-native conditions. Amino acid composition largely determines the non specific properties of peptides, on the basis of the physicochemical properties of the side chains. The resultant effects on peptides' functional properties include influences on the conformation, structural dynamics and binding affinities within the peptide interactome. Here, we studied the effect of substituting oxidation-prone methionine (Met) with non-oxidizable norleucine (Nle) in the model alpha-helical antimicrobial peptide PGLa, through systematic comparison of PGLa with the (2)Met/(2)Nle mutant. Both peptides were evaluated for their bacteriostatic and hemolytic activities (using in situ assays), for their conformational preferences in isotropic solutions (using circular dichroism spectropolarimetry) and for their abilities to modulate membrane curvature (using a solid-state (31)P NMR assay). We determined the membrane-bound states in detail and characterized the orientational dynamics of both peptides in oriented phospholipid membranes by solid-state (19)F NMR spectroscopy. On the one hand, the bioactivity results, the structure in the diluted membrane-mimicking environments and the strong inhibition of the negative membrane curvature were comparable between PGLa and the mutant. On the other hand, the alignments in DMPC bilayer were qualitatively the same but differed in absolute values - the more hydrophobic Nle residue inserted deeper in the membrane core. Furthermore, the mutant peptide displayed a significantly reduced ability to re-orient from the monomeric, surficial to the putative dimeric, tilted state. Overall, these results confirm the functional isosterism of Nle and Met in the helical membrane active peptides but highlight differences in the ways in which the two residues affect non-specific binding to the lipid bilayer and homomeric peptide-peptide interactions. PMID- 27267704 TI - Effect of ethanol perturbation on viscosity and permeability of an inner membrane in Bacillus subtilis spores. AB - In this work, we investigated how a combination of ethanol and high temperature (70 degrees C), affect the properties of the inner membrane of Bacillus subtilis spores. We observed membrane permeabilization for ethanol concentrations >=50%, as indicated by the staining of the spores' DNA by the cell impermeable dye Propidium Iodide. The loss of membrane integrity was also confirmed by a decrease in the peak corresponding to dipicolinic acid using infrared spectroscopy. Finally, the spore refractivity (as measured by phase contrast microscopy) was decreased after the ethanol-heat treatment, suggesting a partial rehydration of the protoplast. Previously we have used fluorescent lifetime imaging microscopy (FLIM) combined with the fluorescent molecular rotor Bodipy-C12 to study the microscopic viscosity in the inner membrane of B. subtilis spores, and showed that at normal conditions it is characterized by a very high viscosity. Here we demonstrate that the ethanol/high temperature treatment led to a decrease of the viscosity of the inner membrane, from 1000cP to 860cP for wild type spores at 50% of ethanol. Altogether, our present work confirms the deleterious effect of ethanol on the structure of B. subtilis spores, as well as demonstrates the ability of FLIM - Bodipy-C12 to measure changes in the microviscosity of the spores upon perturbation. PMID- 27267705 TI - Neural indices of phonemic discrimination and sentence-level speech intelligibility in quiet and noise: A mismatch negativity study. AB - Successful speech communication requires the extraction of important acoustic cues from irrelevant background noise. In order to better understand this process, this study examined the effects of background noise on mismatch negativity (MMN) latency, amplitude, and spectral power measures as well as behavioral speech intelligibility tasks. Auditory event-related potentials (AERPs) were obtained from 15 normal-hearing participants to determine whether pre-attentive MMN measures recorded in response to a consonant (from /ba/ to /bu/) and vowel change (from /ba/ to /da/) in a double-oddball paradigm can predict sentence-level speech perception. The results showed that background noise increased MMN latencies and decreased MMN amplitudes with a reduction in the theta frequency band power. Differential noise-induced effects were observed for the pre-attentive processing of consonant and vowel changes due to different degrees of signal degradation by noise. Linear mixed-effects models further revealed significant correlations between the MMN measures and speech intelligibility scores across conditions and stimuli. These results confirm the utility of MMN as an objective neural marker for understanding noise-induced variations as well as individual differences in speech perception, which has important implications for potential clinical applications. PMID- 27267706 TI - Relative blood loss and operative time can predict length of stay following orthognathic surgery. AB - The aim of this study was to investigate the length of stay (LOS) following orthognathic surgery and thereby to establish a benchmark. The secondary aim was to identify predictors of postoperative LOS following orthognathic surgery. Patients were treated consecutively during the period 2010 to 2012. Inclusion criteria were (1) patient age >=18 years, and (2) surgery involving a three-piece Le Fort I osteotomy, or a bilateral sagittal split osteotomy (BSSO), or bimaxillary surgery. A total of 335 patients were included. The following data were recorded: height, weight, body mass index (BMI), age, sex, operative time, intraoperative blood loss, and type of surgery. LOS was defined as the duration of time from date of surgery to date of discharge. The average LOS was 1.3 days following Le Fort I osteotomy, 1.3 days following BSSO, and 1.8 days following bimaxillary surgery. In the multivariate regression model (R(2)=0.11), predictors of a prolonged LOS were operative time (P<0.001) and relative blood loss (P=0.002). No significant effect of age, BMI, sex, or treatment on LOS was observed. The short duration of LOS found in this study supports the possibility of increasing outpatient pathways for selected patients. PMID- 27267707 TI - Temporomandibular joint arthroscopy technique using a single working cannula. AB - The traditional arthroscopy technique includes the creation of three ports in order to enable visualization, operation, and arthrocentesis. The aim of this study was to assess an advanced temporomandibular joint (TMJ) arthroscopy technique that requires only a single cannula, through which a one-piece instrument containing a visualization canal, irrigation canal, and a working canal is inserted, as an alternative to the traditional double-puncture technique. This retrospective study assessed eight patients (13 TMJs) with pain and/or limited range of movement that was refractory to conservative therapy, who were treated between June 2015 and December 2015. The temporomandibular joint disorder (TMD) was diagnosed by physical examination and mouth opening measurements. The duration of surgery was recorded and compared to that documented for traditional arthroscopies performed by the same surgeon. Operative single-cannula arthroscopy (OSCA) was performed using a holmium YAG (Ho:YAG) 230MUm fibre laser for ablation. The OSCA technique proved effective in improving mouth opening in all patients (mean increase 9.12+/-1.96mm) and in reducing pain (mean visual analogue scale decrease of 3.25+/-1.28). The operation time was approximately half that of the traditional technique. The OSCA technique is as efficient as the traditional technique, is simple to learn, and is simpler to execute. PMID- 27267708 TI - Primary delayed onset craniosynostosis in a child demonstrated by serial computed tomography imaging. AB - Primary delayed onset craniosynostosis is a rarely reported phenomenon. The unique case of a 2-year-old boy who had computed tomography (CT) scans performed 20 months apart demonstrating the post-gestational development of sagittal suture craniosynostosis is presented. The otherwise healthy male initially presented to the emergency department at age 7 months with soft tissue swelling over his left parietal region secondary to a fall. A CT scan revealed a possible left parietal skull fracture without intracranial pathology and patent cranial sutures with a normocephalic calvarial configuration. Twenty months later, his paediatrician referred the boy to the craniofacial service for evaluation of progressive dolichocephaly. A new CT scan showed complete fusion of the sagittal suture with resultant biparietal narrowing, frontal bossing, and occipital prominence. The patient subsequently underwent uncomplicated frontoparietal craniotomy with calvarial vault reconstruction. Prior reports in the literature of cases of non syndromic primary delayed onset craniosynostosis all lack 'pre-synostosis' CT imaging that proves post-birth patency of the cranial sutures. This case report documents CT demonstrating true primary delayed onset craniosynostosis. PMID- 27267709 TI - Every day I'm rufflin': Calcium sensing and actin dynamics in the growth factor independent membrane ruffling of professional phagocytes. AB - Professional phagocytes continuously extend dynamic, actin-driven membrane protrusions. These protrusions, often referred to as membrane ruffles, serve a critical role in the essential phagocyte processes of macropinocytosis and phagocytosis. Small GTPases, such as RAC1/2, spatially and temporally regulate membrane ruffle formation. We have recently shown that extracellular calcium regulates the elaboration of membrane ruffles primarily through the synthesis of phosphatidic acid (PtdOH) at the plasma membrane. RAC1/2 guanine nucleotide exchange factors harbouring polybasic stretches are recruited by PtdOH to sites of ruffle formation. Here we discuss our findings and offer perspectives on how the regulation of dynamic actin structures at the plasma membrane by small GTPases is a critical component of phagocyte function. PMID- 27267710 TI - Can Probiotics Reduce Inflammation and Enhance Gut Immune Health in People Living with HIV: Study Designs for the Probiotic Visbiome for Inflammation and Translocation (PROOV IT) Pilot Trials. AB - OBJECTIVES: Despite substantial improvements in HIV outcomes with combination antiretroviral therapy (cART), morbidity and mortality remain above population norms. The gut mucosal immune system is not completely restored by cART, and the resultant microbial translocation may contribute to chronic inflammation, inadequate CD4 T-cell recovery, and increased rates of serious non-AIDS events. Since the microbial environment surrounding a CD4 T cell may influence its development and function, we hypothesize that probiotics provided during cART might reduce inflammation and improve gut immune health in HIV-positive treatment naive individuals (PROOV IT I) and individuals with suboptimal CD4 recovery on cART (PROOV IT II). METHODS: These prospective, double-blinded, randomized, placebo-controlled, multicenter pilot studies will assess the impact of the probiotic Visbiome at 900 billion bacteria daily. Forty HIV positive cART-naive men will be randomized in the PROOV IT I study, coincident with antiretroviral initiation, and be followed for 24 weeks. In PROOV IT II, 36 men on cART, but with a CD4 T-cell count below 350 cells/mm(3) will be followed for 48 weeks. The primary outcome for both studies is the comparison of blood CD8 T-cell immune activation. Secondary analyses will include comparison of blood inflammatory biomarkers, microbial translocation, blood and gut immunology and HIV levels, the bacterial community composition, diet, intestinal permeability, and the safety, adherence and tolerability of the study product. DISCUSSION: These studies will evaluate the ability of probiotics as a safe and tolerable therapeutic intervention to reduce systemic immune activation and to accelerate gut immune restoration in people living with HIV. PMID- 27267712 TI - Effects of Intracerebroventricular Administration of Neuropeptide Y on Metabolic Gene Expression and Energy Metabolism in Male Rats. AB - Neuropeptide Y (NPY) is an important neurotransmitter in the control of energy metabolism. Several studies have shown that obesity is associated with increased levels of NPY in the hypothalamus. We hypothesized that the central release of NPY has coordinated and integrated effects on energy metabolism in different tissues, resulting in increased energy storage and decreased energy expenditure (EE). We first investigated the acute effects of an intracerebroventricular (ICV) infusion of NPY on gene expression in liver, brown adipose tissue, soleus muscle, and sc and epididymal white adipose tissue (WAT). We found increased expression of genes involved in gluconeogenesis and triglyceride secretion in the liver already 2-hour after the start of the NPY administration. In brown adipose tissue, the expression of thermogenic genes was decreased. In sc WAT, the expression of genes involved in lipogenesis was increased, whereas in soleus muscle, the expression of lipolytic genes was decreased after ICV NPY. These findings indicate that the ICV infusion of NPY acutely and simultaneously increases lipogenesis and decreases lipolysis in different tissues. Subsequently, we investigated the acute effects of ICV NPY on locomotor activity, respiratory exchange ratio, EE, and body temperature. The ICV infusion of NPY increased locomotor activity, body temperature, and EE as well as respiratory exchange ratio. Together, these results show that an acutely increased central availability of NPY results in a shift of metabolism towards lipid storage and an increased use of carbohydrates, while at the same time increasing activity, EE, and body temperature. PMID- 27267711 TI - Runx1 Regulates Myeloid Precursor Differentiation Into Osteoclasts Without Affecting Differentiation Into Antigen Presenting or Phagocytic Cells in Both Males and Females. AB - Runt-related transcription factor 1 (Runx1), a master regulator of hematopoiesis, is expressed in preosteoclasts. Previously we evaluated the bone phenotype of CD11b-Cre Runx1(fl/fl) mice and demonstrated enhanced osteoclasts and decreased bone mass in males. However, an assessment of the effects of Runx1 deletion in female osteoclast precursors was impossible with this model. Moreover, the role of Runx1 in myeloid cell differentiation into other lineages is unknown. Therefore, we generated LysM-Cre Runx1(fl/fl) mice, which delete Runx1 equally (~80% deletion) in myeloid precursor cells from both sexes and examined the capacity of these cells to differentiate into osteoclasts and phagocytic and antigen-presenting cells. Both female and male LysM-Cre Runx1(fl/fl) mice had decreased trabecular bone mass (72% decrease in bone volume fraction) and increased osteoclast number (2-3 times) (P < .05) without alteration of osteoblast histomorphometric indices. We also demonstrated that loss of Runx1 in pluripotential myeloid precursors with LysM-Cre did not alter the number of myeloid precursor cells in bone marrow or their ability to differentiate into phagocytizing or antigen-presenting cells. This study demonstrates that abrogation of Runx1 in multipotential myeloid precursor cells significantly and specifically enhanced the ability of receptor activator of nuclear factor-kappaB ligand to stimulate osteoclast formation and fusion in female and male mice without affecting other myeloid cell fates. In turn, increased osteoclast activity in LysM-Cre Runx1(fl/fl) mice likely contributed to a decrease in bone mass. These dramatic effects were not due to increased osteoclast precursors in the deleted mutants and argue that inhibition of Runx1 in multipotential myeloid precursor cells is important for osteoclast formation and function. PMID- 27267714 TI - Endometrial Cancer-Associated FGF18 Expression Is Reduced by Bazedoxifene in Human Endometrial Stromal Cells In Vitro and in Murine Endometrium. AB - Endometrial cancer develops during exposure to estrogen unopposed by progesterone. Traditional formulations for menopausal hormone therapy include a progestin in women with a uterus. However, progestin exposure increases breast cancer risk in postmenopausal women. Alternatives to progestin include bazedoxifene (BZA), a selective estrogen receptor modulator, which prevents estrogen induced endometrial hyperplasia in clinical trials. Molecular mechanisms responsible for BZA's antiproliferative effect are not fully elucidated. We profiled endometrial adenocarcinoma, hyperplasia, and normal proliferative endometrium for differential expression in genes known to be regulated by estrogens or progesterone. Fibroblast growth factor (FGF)18, a paracrine growth factor promoting epithelial proliferation, was significantly increased in adenocarcinoma. Progesterone represses FGF18 by inducing heart and neural crest derivatives expressed transcript 2 (HAND2) in stromal cells. Notably, we confirmed lower HAND2 mRNA in adenocarcinoma, along with higher FGF tyrosine kinase receptor 2 and E74-like factor 5, collectively promoting FGF18 activity. We hypothesized BZA reduces epithelial proliferation by inhibiting FGF18 synthesis in stromal cells. To determine whether BZA regulates FGF18, we treated primary stromal cells with BZA or vehicle. In vitro, BZA reduced FGF18, but did not affect, HAND2. CD1 female mice received either BZA, conjugated estrogen (CE), or combined BZA/CE for 8 weeks. CE-treated mice had nearly 3-fold higher FGF18 expression. In contrast, BZA-treated mice, alone or with CE, had similar FGF18 as controls. Unexpectedly, BZA, alone or with CE, reduced HAND2 more than 80%, differing from progesterone regulation. Reduction of FGF18 is a potential mechanism by which BZA reduces endometrial proliferation and hyperplasia induced by estrogens. However, BZA works independently of HAND2, revealing a novel mechanism for progestin-free hormone therapy in postmenopausal women. PMID- 27267713 TI - Angiotensin Type-2 Receptors Influence the Activity of Vasopressin Neurons in the Paraventricular Nucleus of the Hypothalamus in Male Mice. AB - It is known that angiotensin-II acts at its type-1 receptor to stimulate vasopressin (AVP) secretion, which may contribute to angiotensin-II-induced hypertension. Less well known is the impact of angiotensin type-2 receptor (AT2R) activation on these processes. Studies conducted in a transgenic AT2R enhanced green fluorescent protein reporter mouse revealed that although AT2R are not themselves localized to AVP neurons within the paraventricular nucleus of the hypothalamus (PVN), they are localized to neurons that extend processes into the PVN. In the present set of studies, we set out to characterize the origin, phenotype, and function of nerve terminals within the PVN that arise from AT2R enhanced green fluorescent protein-positive neurons and synapse onto AVP neurons. Initial experiments combined genetic and neuroanatomical techniques to determine that gamma-aminobutyric acid (GABA)ergic neurons derived from the peri-PVN area containing AT2R make appositions onto AVP neurons within the PVN, thereby positioning AT2R to negatively regulate neuroendocrine secretion. Subsequent patch-clamp electrophysiological experiments revealed that selective activation of AT2R in the peri-PVN area using compound 21 facilitates inhibitory (ie, GABAergic) neurotransmission and leads to reduced activity of AVP neurons within the PVN. Final experiments determined the functional impact of AT2R activation by testing the effects of compound 21 on plasma AVP levels. Collectively, these experiments revealed that AT2R expressing neurons make GABAergic synapses onto AVP neurons that inhibit AVP neuronal activity and suppress baseline systemic AVP levels. These findings have direct implications in the targeting of AT2R for disorders of AVP secretion and also for the alleviation of high blood pressure. PMID- 27267715 TI - Bacterial community composition and structure in an Urban River impacted by different pollutant sources. AB - Microbial communities in terrestrial fresh water are diverse and dynamic in composition due to different environmental factors. The goal of this study was to undertake a comprehensive analysis of bacterial composition along different rivers and creeks and correlate these to land-use practices and pollutant sources. Here we used 454 pyrosequencing to determine the total bacterial community composition, and bacterial communities that are potentially of fecal origin, and of relevance to water quality assessment. The results were analyzed using UniFrac coupled with principal coordinate analysis (PCoA) to compare diversity, abundance, and community composition. Detrended correspondence analysis (DCA) and canonical correspondence analysis (CCA) were used to correlate bacterial composition in streams and creeks to different environmental parameters impacting bacterial communities in the sediment and surface water within the watershed. Bacteria were dominated by the phyla Proteobacteria, Bacteroidetes, Acidobacteria, and Actinobacteria, with Bacteroidetes significantly (P<0.001) higher in all water samples than sediment, where as Acidobacteria and Actinobacteria where significantly higher (P<0.05) in all the sediment samples than surface water. Overall results, using the beta diversity measures, coupled with PCoA and DCA showed that bacterial composition in sediment and surface water was significantly different (P<0.001). Also, there were differences in bacterial community composition between agricultural runoff and urban runoff based on parsimony tests using 454 pyrosequencing data. Fecal indicator bacteria in surface water along different creeks and channels were significantly correlated with pH (P<0.01), NO2 (P<0.03), and NH4N (P<0.005); and in the sediment with NO3 (P<0.015). Our results suggest that microbial community compositions were influenced by several environmental factors, and pH, NO2, and NH4 were the major environmental factors driving FIB in surface water based on CCA analysis, while NO3 was the only factor in sediment. PMID- 27267716 TI - Selective toxin effects on faster and slower growing individuals in the formation of hormesis at the population level - A case study with Lactuca sativa and PCIB. AB - Natural plant populations have large phenotypic plasticity that enhances acclimation to local stress factors such as toxin exposures. While consequences of high toxin exposures are well addressed, effects of low-dose toxin exposures on plant populations are seldom investigated. In particular, the importance of 'selective low-dose toxicity' and hormesis, i.e. stimulatory effects, has not been studied simultaneously. Since selective toxicity can change the size distribution of populations, we assumed that hormesis alters the size distribution at the population level, and investigated whether and how these two low-dose phenomena coexist. The study was conducted with Lactuca sativa L. exposed to the auxin-inhibitor 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB) in vitro. In two separate experiments, L. sativa was exposed to 12 PCIB doses in 24 replicates (50 plants/replicate). Shoot/root growth responses at the population level were compared to the fast-growing (>=90% percentile) and the slow-growing subpopulations (<=10% percentile) by Mann-Whitney U testing and dose response modelling. In the formation of pronounced PCIB hormesis at the population level, low-dose effects proved selective, but widely stimulatory which seems to counteract low-dose selective toxicity. The selectivity of hormesis was dose- and growth rate-dependent. Stimulation occurred at lower concentrations and stimulation percentage was higher among slow-growing individuals, but partly or entirely masked at the population level by moderate or negligible stimulation among the faster growing individuals. We conclude that the hormetic effect up to the maximum stimulation may be primarily facilitated by an increase in size of the most slow-growing individuals, while thereafter it seems that mainly the fast growing individuals contributed to the observed hormesis at the population level. As size distribution within a population is related to survival, our study hints that selective effects on slow- and fast-growing individuals may change population dynamics, providing that similar effects can be repeated under field conditions. PMID- 27267717 TI - Fragrances as new contaminants in the Venice lagoon. AB - Fragrance Materials (FMs) are omnipresent components of household and Personal Care Products (PCPs). In spite of their widespread use, little is known about their environmental occurrence. We selected 17 among the longest-lasting and most stable fragrance ingredients that are commercially available, namely: Amberketal, Ambrofix, Amyl Salicylate, Benzyl Salicylate, Bourgeonal, Dupical, Hexyl Salicylate, Isobutavan, Lemonile, Mefranal, Myraldene, Okoumal, Oranger Crystals, Pelargene, Peonile, Tridecene-2-Nitrile, Ultravanil. A new analytical method was developed to quantify FMs in water samples and it was applied to perform the first study about the distribution of these compounds in the surface waters of the city of Venice and its lagoon. Total FMs concentrations range from about 30ngL(-1) to more than 10MUgL(-1) in polluted canals during the low tide. Sewage discharges were supposed to be the main sources of the selected FMs in the environment. Salicylates, oestrogenic and allergenic compounds, were in general the most abundant and widespread components. This study reports for the first time the detection of most of the selected FMs in surface waters and represent the first step to understand their environmental fate. PMID- 27267718 TI - A conceptual framework for hydropeaking mitigation. AB - Hydropower plants are an important source of renewable energy. In the near future, high-head storage hydropower plants will gain further importance as a key element of large-scale electricity production systems. However, these power plants can cause hydropeaking which is characterized by intense unnatural discharge fluctuations in downstream river reaches. Consequences on environmental conditions in these sections are diverse and include changes to the hydrology, hydraulics and sediment regime on very short time scales. These altered conditions affect river ecosystems and biota, for instance due to drift and stranding of fishes and invertebrates. Several structural and operational measures exist to mitigate hydropeaking and the adverse effects on ecosystems, but estimating and predicting their ecological benefit remains challenging. We developed a conceptual framework to support the ecological evaluation of hydropeaking mitigation measures based on current mitigation projects in Switzerland and the scientific literature. We refined this framework with an international panel of hydropeaking experts. The framework is based on a set of indicators, which covers all hydrological phases of hydropeaking and the most important affected abiotic and biotic processes. Effects of mitigation measures on these indicators can be predicted quantitatively using prediction tools such as discharge scenarios and numerical habitat models. Our framework allows a comparison of hydropeaking effects among alternative mitigation measures, to the pre-mitigation situation, and to reference river sections. We further identified key issues that should be addressed to increase the efficiency of current and future projects. They include the spatial and temporal context of mitigation projects, the interactions of river morphology with hydropeaking effects, and the role of appropriate monitoring to evaluate the success of mitigation projects. PMID- 27267719 TI - Common trends in elements? Within- and between-tree variations of wood-chemistry measured by X-ray fluorescence - A dendrochemical study. AB - Element composition of annually resolved tree-rings constitutes a promising biological proxy for reconstructions of environmental conditions and pollution history. However, several methodological and physiological issues have to be addressed before sound conclusions can be drawn from dendrochemical time series. For example, radial and vertical translocation processes of elements in the wood might blur or obscure any dendrochemical signal. In this study, we tested the degree of synchronism of elemental time series within and between trees of one coniferous (Pinus sylvestris L.) and one broadleaf (Castanea sativa Mill.) species growing in conventionally managed forests without direct pollution sources in their surroundings. Micro X-ray fluorescence (MUXRF) analysis was used to establish time series of relative concentrations of multiple elements (Mg, Al, P, Cl, K, Ca, Cr, Mn, Fe and Ni) for different stem heights and stem exposures. We found a common long-term (decadal) trend for most elements in both species, but only little coherence in the high frequency domain (inter-annual variations). Aligning the element curves by cambial age instead of year of ring formation reduced the standard deviations between the single measurements. This points at an influence of age on longer term trends and would require a detrending in order to extract any environmental signal from dendrochemical time series. The common signal was stronger for pine than for chestnut. In pine, many elements show a concentration gradient with higher values towards the tree crown. Mobility of elements in the stem leading to high within- and between-tree variability, as well as a potential age-trend apparently complicate the establishment of reliable dendrochemical chronologies. For future wood-chemical studies, we recommend to work with element ratios instead of single element time series, to consider potential age trends and to analyze more than one sample per tree to account for internal variability. PMID- 27267720 TI - Experimental sulfate amendment alters peatland bacterial community structure. AB - As part of a long-term, peatland-scale sulfate addition experiment, the impact of varying sulfate deposition on bacterial community responses was assessed using 16S tag encoded pyrosequencing. In three separate areas of the peatland, sulfate manipulations included an eight year quadrupling of atmospheric sulfate deposition (experimental), a 3-year recovery to background deposition following 5years of elevated deposition (recovery), and a control area. Peat concentrations of methylmercury (MeHg), a bioaccumulative neurotoxin, were measured, the production of which is attributable to a growing list of microorganisms, including many sulfate-reducing Deltaproteobacteria. The total bacterial and Deltaproteobacterial community structures in the experimental treatment differed significantly from those in the control and recovery treatments that were either indistinguishable or very similar to one another. Notably, the relatively rapid return (within three years) of bacterial community structure in the recovery treatment to a state similar to the control, demonstrates significant resilience of the peatland bacterial community to changes in atmospheric sulfate deposition. Changes in MeHg accumulation between sulfate treatments correlated with changes in the Deltaproteobacterial community, suggesting that sulfate may affect MeHg production through changes in the community structure of this group. PMID- 27267721 TI - Effects of bottom water dissolved oxygen variability on copper and lead fractionation in the sediments across the oxygen minimum zone, western continental margin of India. AB - This study describes the effect of varying bottom-water oxygen concentration on geochemical fractionation (operational speciation) of Cu and Pb in the underneath sediments across the oxygen minimum zone (Arabian Sea) in the west coast of India. Both, Cu and Pb were redistributed among the different binding phases of the sediments with changing dissolved oxygen level (from oxic to hypoxic and close to suboxic) in the bottom water. The average lability of Cu-sediment complexes gradually decreased (i.e., stability increased) with the decreasing dissolved oxygen concentrations of the bottom water. Decreasing bottom-water oxygen concentration increased Cu association with sedimentary organic matter. However, Pb association with Fe/Mn-oxyhydroxide phases in the sediments gradually decreased with the decreasing dissolved oxygen concentration of the overlying bottom water (due to dissolution of Fe/Mn oxyhydroxide phase). The lability of Pb sediment complexes increased with the decreasing bottom-water oxygen concentration. This study suggests that bottom-water oxygen concentration is one of the key factors governing stability and lability of Cu and Pb complexes in the underneath sediment. Sedimentary organic matter and Fe/Mn oxyhydroxide binding phases were the major hosting phases for Cu and Pb respectively in the study area. Increasing lability of Pb-complexes in bottom sediments may lead to positive benthic fluxes of Pb at low oxygen environment. PMID- 27267722 TI - The Australian SuperSite Network: A continental, long-term terrestrial ecosystem observatory. AB - Ecosystem monitoring networks aim to collect data on physical, chemical and biological systems and their interactions that shape the biosphere. Here we introduce the Australian SuperSite Network that, along with complementary facilities of Australia's Terrestrial Ecosystem Research Network (TERN), delivers field infrastructure and diverse, ecosystem-related datasets for use by researchers, educators and policy makers. The SuperSite Network uses infrastructure replicated across research sites in different biomes, to allow comparisons across ecosystems and improve scalability of findings to regional, continental and global scales. This conforms with the approaches of other ecosystem monitoring networks such as Critical Zone Observatories, the U.S. National Ecological Observatory Network; Analysis and Experimentation on Ecosystems, Europe; Chinese Ecosystem Research Network; International Long Term Ecological Research network and the United States Long Term Ecological Research Network. The Australian SuperSite Network currently involves 10 SuperSites across a diverse range of biomes, including tropical rainforest, grassland and savanna; wet and dry sclerophyll forest and woodland; and semi-arid grassland, woodland and savanna. The focus of the SuperSite Network is on using vegetation, faunal and biophysical monitoring to develop a process-based understanding of ecosystem function and change in Australian biomes; and to link this with data streams provided by the series of flux towers across the network. The Australian SuperSite Network is also intended to support a range of auxiliary researchers who contribute to the growing body of knowledge within and across the SuperSite Network, public outreach and education to promote environmental awareness and the role of ecosystem monitoring in the management of Australian environments. PMID- 27267724 TI - Anthropogenic and natural methane emissions from a shale gas exploration area of Quebec, Canada. AB - The increasing number of studies on the determination of natural methane in groundwater of shale gas prospection areas offers a unique opportunity for refining the quantification of natural methane emissions. Here methane emissions, computed from four potential sources, are reported for an area of ca. 16,500km(2) of the St. Lawrence Lowlands, Quebec (Canada), where Utica shales are targeted by the petroleum industry. Methane emissions can be caused by 1) groundwater degassing as a result of groundwater abstraction for domestic and municipal uses; 2) groundwater discharge along rivers; 3) migration to the surface by (macro- and micro-) diffuse seepage; 4) degassing of hydraulic fracturing fluids during first phases of drilling. Methane emissions related to groundwater discharge to rivers (2.47*10(-4) to 9.35*10(-3)Tgyr(-1)) surpass those of diffuse seepage (4.13*10( 6) to 7.14*10(-5)Tgyr(-1)) and groundwater abstraction (6.35*10(-6) to 2.49*10( 4)Tgyr(-1)). The methane emission from the degassing of flowback waters during drilling of the Utica shale over a 10- to 20-year horizon is estimated from 2.55*10(-3) to 1.62*10(-2)Tgyr(-1). These emissions are from one third to sixty six times the methane emissions from groundwater discharge to rivers. This study shows that different methane emission sources need to be considered in environmental assessments of methane exploitation projects to better understand their impacts. PMID- 27267723 TI - Microcystin-LR bioaccumulation and depuration kinetics in lettuce and arugula: Human health risk assessment. AB - Microcystin-LR (MC-LR) is one of the most toxic and common microcystins (MCs) variant found in aquatic ecosystems. Little is known about the possibility of recovering microcystins contaminated agricultural crops. The objectives of this study were to determine the bioaccumulation and depuration kinetics of MC-LR in leaf tissues of lettuce and arugula, and estimate the total daily intake (ToDI) of MC-LR via contaminated vegetables by humans. Arugula and lettuce were irrigated with contaminated water having 5 and 10MUgL(-1) of MC-LR for 7days (bioaccumulation), and subsequently, with uncontaminated water for 7days (depuration). Quantification of MC-LR was performed by LC-MS/MS. The one compartment biokinetic model was employed for MC-LR bioaccumulation and depuration data analysis. MC-LR was only accumulated in lettuce. After 7days of irrigation with uncontaminated water, over 25% of accumulated MC-LR was still retained in leaf tissues of plants treated with 10MUgL(-1) MC-LR. Total daily toxin intake by adult consumers (60kg-bw) exceeded the 0.04MUgMC-LRkg(-1) limit recommended by WHO. Bioaccumulation was found to be linearly proportional to the exposure concentration of the toxin, increasing over time; and estimated to become saturated after 30days of uninterrupted exposure. On the other hand, MC-LR depuration was less efficient at higher exposure concentrations. This is because biokinetic half-life calculations gave 2.9 and 3.7days for 5 and 10MUgL(-1) MC-LR treatments, which means 29-37days are required to eliminate the toxin. For the first time, our results demonstrated the possibility of MC-LR decontamination of lettuce plants. PMID- 27267725 TI - Spatial variations in the consumption of illicit stimulant drugs across Australia: A nationwide application of wastewater-based epidemiology. AB - Obtaining representative information on illicit drug use and patterns across a country remains difficult using surveys because of low response rates and response biases. A range of studies have used wastewater-based epidemiology (WBE) as a complementary approach to monitor community-wide illicit drug use. In Australia, no large-scale WBE studies have been conducted to date to reveal illicit drug use profiles in a national context. In this study, we performed the first Australia-wide WBE monitoring to examine spatial patterns in the use of three illicit stimulants (cocaine, as its human metabolite benzoylecgonine; methamphetamine; and 3,4-methylendioxymethamphetamine (MDMA)). A total of 112 daily composite wastewater samples were collected from 14 wastewater treatment plants across four states and two territories. These covered approximately 40% of the Australian population. We identified and quantified illicit drug residues using liquid chromatography coupled with tandem mass spectrometry. There were distinctive spatial patterns of illicit stimulant use in Australia. Multivariate analyses showed that consumption of cocaine and MDMA was higher in the large cities than in rural areas. Also, cocaine consumption differed significantly between different jurisdictions. Methamphetamine consumption was more similar between urban and rural locations. Only a few cities had elevated levels of use. Extrapolation of the WBE estimates suggested that the annual consumption was 3tonnes for cocaine and 9tonnes combined for methamphetamine and MDMA, which outweighed the annual seizure amount by 25 times and 45 times, respectively. These ratios imply the difficulty of detecting the trafficking of these stimulants in Australia, possibly more so for methamphetamine than cocaine. The obtained spatial pattern of use was compared with that in the most recent national household survey. Together both WBE and survey methods provide a more comprehensive evaluation of drug use that can assist governments in developing policies to reduce drug use and harm in the communities. PMID- 27267726 TI - PAH related effects on fish in sedimentation ponds for road runoff and potential transfer of PAHs from sediment to biota. AB - Road runoff is an important source of pollution to the aquatic environment, and sedimentation ponds have been installed to mitigate effects on the aquatic environment. The purpose of this study was to investigate if a) fish from sedimentation ponds were affected by road pollution and; b) the transfer of PAHs from road runoff material to aquatic organisms was substantial. Minnow from a sedimentation pond (Skullerud) near Oslo (Norway) had higher levels of CYP1A enzyme and DNA stand breaks than minnow from the nearby river, but high concentrations of PAH-metabolites in bile revealed that both populations were highly exposed. Principal component analysis revealed that CYP1A and age of fish were correlated, while levels of PAH-metabolites were not correlated to CYP1A or DNA damage. Minnow from a lake un-affected by traffic had much lower levels of PAH-metabolites than the exposed fish, and also an improved condition. The latter results indicate that fish health was affected by road runoff. A closer investigation of PAH levels of the ecosystems of two sedimentation ponds (Skullerud and Vassum) and nearby environments were conducted. The concentration of the 16 EPA PAHs in sediments of the sedimentation ponds were high (1900 4200ngg(-1)), and even higher levels were observed in plants. Principal component analysis of selected ion chromatograms of PAHs showed a clear separation of plants vs. sediments. The plants preferentially accumulated the high molecular PAHs, both from sedimentation ponds with a petrogenic PAH isomer ratio in sediments; and from a lake with pyrogenic PAH isomer ratio in sediments. PMID- 27267728 TI - Toxicological implications and laxative potential of ethanol root extract of Morella serrata in loperamide-induced constipated Wistar rats. AB - CONTEXT: Morella serrata L. (Myricaceae) is commonly used in South Africa to treat several diseases including constipation. OBJECTIVES: This study investigated toxicological implications and laxative potential of the ethanol root extract of the plant. MATERIALS AND METHODS: While normal control animals were placed on sterile placebo, the loperamide-constipated rats were treated with the extract at 75, 150 and 300 mg/kg doses for 7 days, and their feeding patterns and faecal properties were monitored. Gastrointestinal transit ratio and the toxicity profile of the tested doses were thereafter evaluated. RESULTS: The significantly increased faecal volume (192.08%), feed (63.63%), water intake (55.97%) and improved intestinal motility (95.05%) in the constipated rats following treatment with the extract (at 300 mg/kg) suggested laxative potential of the extract. The 1.5-2.0-fold normalization of the platelets, erythrocytes and leukocytes counts in the extract-treated constipated rats suggests its non haematotoxic tendency. Furthermore, the extract (at the highest investigated dose) reversed the attenuation in the concentrations of the electrolytes (0.5-2 fold), total protein (62.12%) and albumin (55.88%) in the constipated animals as well as attenuated activities of hepatic enzymes (0.5-3.0-fold) and levels of urea (126.67%), creatinine (40.32%), cholesterol (3-fold) and triglycerides (9 fold). These further support its non-toxic and therapeutic attributes against constipation. CONCLUSION: Overall, the effect exhibited by M. serrata in this study competed well with Senokot (standard drug) and proved that it may be relatively safe and with excellent laxative potential, thus, supporting its pharmacological applications in South Africa. PMID- 27267727 TI - Effect of steam activated biochar application to industrially contaminated soils on bioavailability of polycyclic aromatic hydrocarbons and ecotoxicity of soils. AB - The aim of this study was to determine the effect of steam activation of biochars on the immobilization of freely dissolved (Cfree) and bioaccessible fraction (Cbioacc) of PAHs in soils. Additionally, the toxicity to various organisms like Vibrio fischeri, Lepidium sativum and Folsomia candida was measured before and after the amendment of biochars to soils. Three biochars produced from willow, coconut and wheat straw were steam activated and added to three different soils with varying content and origin of PAHs (coke vs. bitumen). The soils with the addition of the biochars (activated and non-activated) were incubated for a period of 60days. Steam activation of the biochars resulted in more pronounced reduction of both Cfree and Cbioacc. The range of the increase in effectiveness was from 10 to 84% for Cfree and from 50 to 99% for Cbioacc. In contrast, the effect of activation on the toxicity of the soils studied varied greatly and was specific to a particular test and soil type. Essentially, biochar activation did not result in a change of phytotoxicity, but it increased or decreased (depending on the parameter, type of biochar, contaminant source, and soil and soil type) the toxic effect to F. candida, and decreased the toxicity of leachates to V. fischeri. PMID- 27267729 TI - Decision sharing in preventive cardiology. PMID- 27267731 TI - Induction of Haustorium Development by Sphaeropsidones in Radicles of the Parasitic Weeds Striga and Orobanche. A Structure-Activity Relationship Study. AB - Crop attack by parasitic weeds such as Striga and Orobanche occurs through developmental processes triggered by host chemodetection. Seeds of those weed species remain dormant in the soil until germination is triggered by host root exudates. The development of haustorium, a parasitic plant organ that invades the host to withdraw its nutrients, is also initiated in Orobanchaceae by host molecular cues. The induction of haustorium development by exogenous signals has previously been reported for Striga but not for Orobanche species. In this work, we demonstrate that sphaeropsidone and epi-sphaeropsidone, two phytotoxic cyclohexene oxides isolated from the fungus Diplodia cupressi, a causal agent of cypress canker, induce haustorium development in radicles of the parasitic weeds Striga hermonthica, Orobanche crenata, and Orobanche cumana. This is the first report of chemical stimulation of haustorium development in radicles of Orobanche in the absence of host. In addition, SAR studies were carried out by testing the haustorium-inducing activity of the natural cyclohexene oxides, seven already known and four new hemisynthetic derivatives, in O. cumana, O. crenata, and S. hermonthica, to find a molecular specificity model required for haustorium induction. The results suggested that the haustorium-inducing activity is due to the possibility to convert the natural sphaeropsidone and natural and hemisynthetic derivatives in the corresponding 3-methoxyquinone and that the stereochemistry at C-5 also seems to affect this activity. PMID- 27267730 TI - Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-kappaB-dependent manner. AB - BACKGROUND: Atherosclerosis is a chronic inflammatory disease and represents the leading cause of morbidity and mortality throughout the world. Accumulating evidences have showed that Dihydrocapsaicin (DHC) has been found to exert multiple pharmacological and physiological effects. Nevertheless, the effects and possible mechanism of DHC on proinflammatory response remain largely unexplained. METHODS AND RESULTS: We found that DHC markedly upregulated NFIA and suppressed NF-kappaB expression in THP-1 macrophages. Up-regulation of proinflammatory cytokines induced by LPS including TNF-alpha, IL-1beta and IL-6 were markedly suppressed by DHC treatment. We also observed that protein level of NFIA was significantly increased while NF-kappaB and proinflammatory cytokines were decreased by DHC treatment in apoE(-/-) mice. Lentivirus-mediated overexpression of NFIA suppressed NF-kappaB and proinflammatory cytokines expression both in THP 1 macrophages and plaque tissues of apoE-/- mice. Moreover, treatment with lentivirus-mediated overexpression of NFIA made the down-regulation of DHC on NF kappaB and proinflammatory cytokines expression notably accentuated in THP-1 macrophages and apoE(-/-) mice. In addition, treatment with siRNA targeting NF kappaB accentuated the suppression of proinflammatory cytokines by lentivirus mediated overexpression of NFIA. CONCLUSION: These observations demonstrated that DHC can significantly decrease proinflammatory cytokines through enhancing NFIA and inhibiting NF-kappaB expression and thus DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other disorders. PMID- 27267732 TI - Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron. AB - In the process of implementation and innovation of paediatric dosage forms, buccal films for transmucosal administration of drug represent one of the most interesting approach. In fact, films are able to provide an extended duration of activity allowing minimal dosage and frequency and offer an exact and flexible dose, associated with ease of handling. The objective of the present study was to develop polymeric films for the sustained release of ondansetron hydrochloride, a selective inhibitor of 5-HT3 receptors indicated in paediatrics for the prevention and treatment of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy and postoperatively. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of hydroxypropylmethylcellulose (HPMC) with chitosan (CH) or sodium hyaluronate (HA) or gelatin (GEL) and characterized for their physico-chemical and functional properties. The presence of HA, GEL and CH did not improve the mucoadhesive properties of HPMC film. The inclusion of GEL and CH in HPMC film increased in vitro drug release with respect to the inclusion of HA, although films containing HA showed the highest water uptake. Moreover in agreement with the release behaviour, the inclusion of CH and GEL provided higher drug permeation through porcine buccal mucosa with respect to HPMC film and ensured linear permeation profiles of drug. PMID- 27267733 TI - Supramolecular Nanostructure Formation of Coassembled Amyloid Inspired Peptides. AB - Characterization of amyloid-like aggregates through converging approaches can yield deeper understanding of their complex self-assembly mechanisms and the nature of their strong mechanical stability, which may in turn contribute to the design of novel supramolecular peptide nanostructures as functional materials. In this study, we investigated the coassembly kinetics of oppositely charged short amyloid-inspired peptides (AIPs) into supramolecular nanostructures by using confocal fluorescence imaging of thioflavin T binding, turbidity assay and in situ small-angle X-ray scattering (SAXS) analysis. We showed that coassembly kinetics of the AIP nanostructures were consistent with nucleation-dependent amyloid-like aggregation, and aggregation behavior of the AIPs was affected by the initial monomer concentration and sonication. Moreover, SAXS analysis was performed to gain structural information on the size, shape, electron density, and internal organization of the coassembled AIP nanostructures. The scattering data of the coassembled AIP nanostructures were best fitted into to a combination of polydisperse core-shell cylinder (PCSC) and decoupling flexible cylinder (FCPR) models, and the structural parameters were estimated based on the fitting results of the scattering data. The stability of the coassembled AIP nanostructures in both fiber organization and bulk viscoelastic properties was also revealed via temperature-dependent SAXS analysis and oscillatory rheology measurements, respectively. PMID- 27267734 TI - An Alternative Route to Pentavalent Postperovskite. AB - Two different high-pressure and -temperature synthetic routes have been used to produce only the second-known pentavalent CaIrO3-type oxide. Postperovskite NaOsO3 has been prepared from GdFeO3-type perovskite NaOsO3 at 16 GPa and 1135 K. Furthermore, it has also been synthesized at the considerably lower pressure of 6 GPa and 1100 K from a precursor of hexavalent Na2OsO4 and nominally pentavalent KSbO3-like phases. The latter synthetic pathway offers a new lower-pressure route to the postperovskite form, one that completely foregoes any perovskite precursor or intermediate. This work suggests that postperovskite can be obtained in other compounds and chemistries where generalized rules based on the perovskite structure may not apply or where no perovskite is known. One more obvious consequence of our second route is that perovskite formation may even mask and hinder other less extreme chemical pathways to postperovskite phases. PMID- 27267735 TI - Energetic Salts Based on 3,5-Bis(dinitromethyl)-1,2,4-triazole Monoanion and Dianion: Controllable Preparation, Characterization, and High Performance. AB - Molecular modification of known explosives is considered to be an efficient route to design new energetic materials. A new family of energetic salts based on the 3,5-bis(dinitromethyl)-1,2,4-triazole monoanion and dianion were controllably synthesized by using 1-diamino-2,2-dinitroethene as a precursor. X-ray structure determination of monohydrazinium 3,5-bis(dinitromethyl)-1,2,4-triazolate (5) and monoammonium (6) and diammonium 3,5-bis(dinitromethyl)-1,2,4-triazolate hydrate (8.H2O) further confirmed the structures of these anions. In addition, as supported by X-ray data, in the monoanion system, the roving proton on the ring nitrogen rather than on the gem-dinitro carbon results in extensive hydrogen bonding interactions and higher packing coefficients. Interestingly, 5 and 6 possess the highest calculated crystal densities, 1.965 and 1.957 g cm(-3) at 150 K, for hydrazinium and ammonium energetic salts, respectively. Energetic evaluation indicates that 5 (detonation velocity vD = 9086 m s(-1); detonation pressure P = 38.7 GPa) and 6 (vD, 9271 m s(-1); P = 41.0 GPa) exhibit great detonation properties, superior to those of current highly explosive benchmarks, such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and octahydro-1,3,5,7 tetranitro-1,3,5,7-tetrazocine (HMX). PMID- 27267736 TI - Targeting the Androgen Receptor: Remaining questions and future directions. PMID- 27267737 TI - Clinical, prognostic, and therapeutic aspects of urachal carcinoma-A comprehensive review with meta-analysis of 1,010 cases. AB - BACKGROUND AND OBJECTIVES: Urachal carcinoma (UrC) is a rare and poorly investigated disease. Our current knowledge is mainly based on single institutional studies. Despite growing interest in UrC, the included case numbers in recently published studies are still low. Therefore, we aimed to provide a comprehensive meta-analysis on the clinical, prognostic, and therapeutic aspects of UrC. METHODS: A systematic Medline/PubMed search was performed on UrC using the terms "urachal carcinoma," "urachal cancer," and "urachus." Original articles and reviews in English language with case numbers>10 were selected. RESULTS: The vast majority (91%, 489/532) of UrCs are diagnosed at later stages (Sheldon>=III) when the tumor invades the urinary bladder. About 21% (136/646) of UrC patients have distant metastasis at first presentation. Although for patients with non metastatic UrC surgical treatment provides an acceptable disease control, the systemic treatment of patients with progressed/metastatic UrC-in lack of prospective clinical trials-are less well established. Comparing cisplatin-based and 5-FU-based therapies in 74 published UrC cases, we found the latter to be superior in terms of radiographic response rates (9% vs. 44%, P = 0.043), but the combination of these 2 therapies provided the lowest progression rate (14%) with a similarly high response rate (43%). CONCLUSIONS: Owing to the lack of evidence based guidelines, the therapy of UrC remains challenging. Given the infrequency of UrC, large prospective studies comparing different systemic therapies can hardly be conducted. Our metadata indicates that 5-FU-containing chemotherapy regimens are more effective than cisplatin-based treatment modalities, whereas their combination seems to provide the strongest antitumor effect. Nevertheless, in the lack of evidences from prospective clinical trials, therapeutic decision making necessarily remains on an individual basis. In this situation, targeted therapies may provide a reasonable alternative. Therefore, better understanding of the molecular background of UrC is needed to rationalize treatment decisions in UrC. PMID- 27267738 TI - Tailpipe emissions from gasoline direct injection (GDI) and port fuel injection (PFI) vehicles at both low and high ambient temperatures. AB - Vehicle emissions are greatly influenced by various factors that are related to engine technology and driving conditions. Only the fuel injection method and ambient temperature are investigated in this research. Regulated gaseous and particulate matter (PM) emissions from two advanced gasoline-fueled vehicles, one with direct fuel injection (GDI) and the other with port fuel injection (PFI), are tested with conventional gasoline and ethanol-blended gasoline (E10) at both 7 degrees C and 30 degrees C. The total particle number (PN) concentrations and size distributions are monitored with an Electrical Low Pressure Impactor (ELPI(+)). The solid PN concentrations are measured with a condensation particle counter (CPC) after removing volatile matters through the particle measurement program (PMP) system. The results indicate that decreasing the ambient temperature from 30 degrees C to -7 degrees C significantly increases the fuel consumption and all measured emissions except for NOx. The GDI vehicle exhibits lower fuel consumption than the PFI vehicle but emits more total hydrocarbons (THC), PM mass and solid PN emissions at 30 degrees C. The adaptability of GDI technology appears to be better than that of PFI technology at low ambient temperature. For example, the CO, THC and PM mass emission factors of the PFI vehicle are higher than those of the GDI vehicle and the solid PN emission factors are comparable in the cold-start tests at -7 degrees C. Specifically, during start-up the particulate matter emissions of the PFI are much higher than the GDI. In most cases, the geometric mean diameter (GMD) of the accumulation mode particles is 58-86 nm for both vehicles, and the GMD of the nucleation mode particles is 10-20 nm. The results suggest that the gaseous and particulate emissions from the PFI vehicle should not be neglected compared to those from the GDI vehicle especially in a cold environment. PMID- 27267739 TI - Field evaluation and calibration of a small axial passive air sampler for gaseous and particle bound polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs. AB - Polycyclic aromatic hydrocarbons (PAHs) and their oxygenated analogues (OPAHs) are ubiquitous air pollutants known to cause adverse health effects. PAH air levels are commonly monitored by active sampling but passive sampling has become popular because of its lower cost and simplicity, which facilitate long-term sampling and increased spatial coverage. However, passive samplers are less suitable for short-term sampling and are in general less accurate than active samplers because they require reliable sampling rate (Rs) measurements for individual analytes under diverse environmental conditions. In this study a small passive sampler designed to sample both particle-bound and gaseous compounds was evaluated and calibrated for PAHs and OPAHs in a traffic environment by co deployment with active samplers for two weeks. Despite the relatively low average air concentrations of PM10 (20 MUg/m(3)), PM2.5 (5 MUg/m(3)), total PAHs (4.2 ng/m(3)), and OPAHs (2.3 ng/m(3)) at the site, detectable quantities (on average 24 times above blank values) of the full range of PAHs and OPAHs were captured, with low variability (average RSD of 16%). This was accomplished by using a Tenax((r)) TA-modified glass fiber substrate that is compatible with highly sensitive thermal desorption GC-MS analysis, which made it possible to achieve detection limits per sample in the pg range. Experiments with inverted samplers revealed that the relative contribution of gravitational settling to the sampling of particles carrying PAHs and OPAHs was around 3.5 times larger than other deposition mechanisms. Average Rs values for individual OPAHs and PAHs were 0.046 +/- 0.03 m(3)/day and 0.12 +/- 0.07 m(3)/day, respectively, with no appreciable difference between the values for particle-associated and gaseous compounds. Furthermore, the Rs values were competitive with other currently used passive samplers if normalized for substrate area. Overall, the new sampler's performance, simplicity and ability to generate relatively time-resolved data make it a promising candidate for diverse SVOC monitoring studies. PMID- 27267740 TI - Location and speciation of gadolinium and yttrium in roots of Zea mays by LA-ICP MS and ToF-SIMS. AB - Increasing production of rare earth elements (REE) might lead to future contamination of the environment. REE have been shown to accumulate in high concentrations in roots of plants. Plant experiments with Zea mays exposed to a nutrient solution containing gadolinium (Gd) or yttrium (Y) with 10 mg L(-1) Gd or Y were carried out to investigate this accumulation behaviour. Total concentrations of 3.17 g kg(-1) and 8.43 g kg(-1) of Gd and Y were measured in treated plant roots. Using a novel combination of laser ablation mass spectrometry and time-of-flight secondary ion mass spectrometry, imaging of location and concentration of Gd and Y was carried out in root thin sections of treated roots. Single spots of elevated REE concentration were found at the epidermis, while inside the cortex, weak signals of Gd(+) and Y(+) were aligning with the root cell structures. The composition of Gd-containing secondary ions proves an REE-oxide phase accumulated at the epidermis, limiting REE availability for further uptake. PMID- 27267741 TI - Feather mercury concentrations in Southern Ocean seabirds: Variation by species, site and time. AB - We studied mercury contamination in 25 seabird species breeding along a latitudinal gradient across the Southern Ocean, from Gough Island (40 degrees S) through Marion Island (47 degrees S) to Byers Peninsula (63 degrees S). Total mercury concentrations in body feather samples of adults caught at breeding colonies from 2008 to 2011 were determined. Krill (Euphausia spp.) and other zooplankton consumers had low mercury concentrations (gentoo penguin Pygoscelis papua, chinstrap penguin Pseudomonas Antarctica, common diving petrel Pelecanoides urinatrix, broad-billed prion Pachyptila vittata; mean levels 308 753 ng g(-1)), whereas seabirds consuming squid or carrion had high mercury concentrations (ascending order: Kerguelen petrel Aphrodroma brevirostris, southern giant petrel Macronectes giganteus, soft-plumaged petrel Pterodroma mollis, sooty albatross Phoebetria fusca, Atlantic petrel Pterodroma incerta, northern giant petrel Macronectes halli, great-winged petrel Pterodroma macroptera; 10,720-28038 ng g(-1)). The two species with the highest mercury concentrations, northern giant petrels and great-winged petrels, bred at Marion Island. Among species investigated at multiple sites, southern giant petrels had higher mercury levels at Marion than at Gough Island and Byers Peninsula. Mercury levels among Byers Peninsula seabirds were low, in two species even lower than levels measured 10 years before at Bird Island, South Georgia. Replicate measurements after about 25 years at Gough Island showed much higher mercury levels in feathers of sooty albatrosses (by 187%), soft-plumaged petrels (53%) and Atlantic petrels (49%). Concentrations similar to the past were detected in southern giant petrels at Gough and Marion islands, and in northern giant petrels at Marion. There were no clear indications that timing of moult or migratory behavior affected mercury contamination patterns among species. Causes of inter site or temporal differences in mercury contamination could not be verified due to a lack of long-term data related to species' diet and trophic levels, which should be collected in future together with data on mercury contamination. PMID- 27267743 TI - Effect of heavy metals and organic matter on root exudates (low molecular weight organic acids) of herbaceous species: An assessment in sand and soil conditions under different levels of contamination. AB - Bioavailability of heavy metals can be modified by different root exudates. Among them, low molecular weight organic acids (LMWOAs) play an important role in this process. Three plant species (Poa annua, Medicago polymorpha and Malva sylvestris), potentially used for phytoremediation, have been assessed for both metal uptake and LMWOAs excretion in contaminated environments with different concentrations of Cd, Cu and Zn. The experiments have been carried out in washed sand and in three contaminated soils where two organic amendments were added (biosolid compost and alperujo compost). The most abundant LMWOAs excreted by all studied plants were oxalic and malic acids, although citric and fumaric acids were also detected. The general tendency was that plants responded to an increase of heavy metal stress releasing higher amounts of LMWOAs. This is an efficient exclusion mechanism reducing the metal uptake and allowing the plant growth at high levels of contamination. In the experiment using wash sand as substrate, the organic acids composition and quantity depended mainly on plant species and metal contamination. M. polymorpha was the species that released the highest concentrations of LMWOAs, both in sand and in soils with no amendment addition, whereas a decrease of these acids was observed with the addition of amendments. Our results established a clear effect of organic matter on the composition and total amount of LMWOAs released. The increase of organic matter and nutrients, through amendments, improved the soil quality reducing phytotoxicity. As a result, organic acids exudates decreased and were solely composed of oxalic acid (except for M. polymorpha). The release of LMWOAs has proved to be an important mechanism against heavy metal stress, unique to each species and modifiable by means of organic amendment addition. PMID- 27267742 TI - Concentrations and patterns of hydroxylated polybrominated diphenyl ethers and polychlorinated biphenyls in arctic foxes (Vulpes lagopus) from Svalbard. AB - Concentrations and patterns of hydroxylated (OH) polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were investigated in liver from arctic foxes (Vulpes lagopus) sampled from Svalbard 1997-2011 (n = 100). The most important OH-PBDE in the arctic foxes was 6-OH-BDE47 detected in 24% of the samples. Relationships between 6-OH-BDE47, delta(13)C and BDE47 suggest that 6-OH BDE47 residues in arctic foxes are related to marine dietary input, while the relative importance of the metabolic/natural origin of this compound remains unclear. 4-OH-CB187 and 4-OH-CB146 were the main OH-PCBs among the analyzed compounds. The OH-PCB pattern in the present arctic foxes indicates that arctic foxes have a capacity to biotransform a wide range of PCBs of different structures. Formation and retention of OH-PCBs was tightly related to PCB exposure. Furthermore, SigmaOH-PCB concentrations were four times higher in the leanest compared to the fattest foxes. Concentrations of 4-OH-CB187 and 4-OH CB146 among the highest contaminated arctic foxes were similar to the previously reported concentrations for polar bears. Given the high endocrine disruptive potential of OH-PCBs, we suggest that endocrine system may be affected by the relatively high OH-PCB residues in the Svalbard arctic fox population. PMID- 27267744 TI - Direct Entry to 4,10-Didesmethyl (9S)-Dihydroerythronolide A via Catalytic Allene Osmylation. AB - Desmethyl erythronolides have emerged as macrolide targets that may prove effective against resistant bacteria. A five-step sequence to 4,10-didesmethyl (9S)-dihydroerythronolide A (1) from known cyclic bis[allene] 13 is reported. Key structural and mechanistic aspects of the synthesis are discussed along with catalytic allene osmylation. An improved route to 13 is also described. PMID- 27267745 TI - Application of freeze-drying in the development of oral drug delivery systems. AB - INTRODUCTION: With continual focus on oral drug delivery systems (ODDS), the role of freeze-drying becomes increasingly valuable. While freeze-drying is fundamentally a desiccation process, the advantageous material properties attributed to freeze-drying extend far beyond the preparation of stable pharmaceutical products. The formulation and process variables are important considerations as they affect the final freeze-dried product characteristics. It is of interest to expound on the principles and effects of freeze-drying in the hope of introducing novel products for applications in the development of ODDS. Areas covered: In this review, basic principles, general formulation and process variables associated with freeze-drying will be covered. The application of freeze-drying in 3 areas: modification of active ingredients, development of novel freeze-dried excipients and development of freeze-dried final dosage forms will be discussed. Expert opinion: As a pharmaceutical unit operation, freeze drying has created new dimensions in the area of oral drug delivery, where the properties of the drugs, excipients and characteristics of the final solid dosage form can be modified by the freeze-drying process. With the emergence of new applications, the role of freeze-drying technology in ODDS is indeed a relevant and promising one. PMID- 27267746 TI - Patterns of metastasis and recurrence in thymic epithelial tumours: longitudinal imaging review in correlation with histological subtypes. AB - AIM: To determine the patterns of metastasis and recurrence in thymic epithelial tumours based on longitudinal imaging studies, and to correlate the patterns with World Health Organization (WHO) histological classifications. MATERIALS AND METHODS: Seventy-seven patients with histopathologically confirmed thymomas (n=62) and thymic carcinomas (n=15) who were followed with cross-sectional follow up imaging after surgery were retrospectively studied. All cross-sectional imaging studies during the disease course were reviewed to identify metastasis or recurrence. The sites of involvement and the time of involvement measured from surgery were recorded. RESULTS: Metastasis or recurrence was noted in 24 (31%) of the 77 patients. Patients with metastasis or recurrence were significantly younger than those without (median age: 46 versus 60, respectively; p=0.0005), and more commonly had thymic carcinomas than thymomas (p=0.002). The most common site of involvement was the pleura (17/24), followed by the lung (9/24), and thoracic nodes (9/24). Abdominopelvic involvement was noted in 12 patients, most frequently in the liver (n=8). Lung metastasis was more common in thymic carcinomas than thymomas (p=0.0005). Time from surgery to the development of metastasis or recurrence was shortest in thymic carcinoma, followed by high-risk thymomas, and was longest in low-risk thymoma (median time in months: 25.1, 68.8, and not reached, respectively; p=0.0015). CONCLUSIONS: The patterns of metastasis and recurrence of thymic epithelial tumours differ significantly across histological subgroups, with thymic carcinomas more commonly having metastasis with shorter length of time after surgery. The knowledge of different patterns of tumour spread may contribute to further understanding of the biological and clinical behaviours of these tumours. PMID- 27267748 TI - Histological and biological comparisons between complete and incomplete discoid lateral meniscus. AB - The discoid lateral meniscus (DLM) is an anatomically abnormal meniscus that covers a greater area of the tibial plateau than the normal meniscus. The DLM is classified into two types: complete (CDLM) and incomplete (ICDLM) types. In this study, we investigated the histological and cell biological characteristics of CDLM and ICDLM. The number of blood vessels, proteoglycan deposition, and collagen distribution were assessed using meniscal tissues. Collagen production was also investigated in CDLM and ICDLM cells. The intercondylar region of the CDLM had a higher number of blood vessels than the inner region of the ICDLM. Safranin O staining density and type II collagen deposition in ICDLM were higher than those in CDLM. Type II collagen-positive cells were higher in ICLDM than in CDLM. CDLM cells showed slender fibroblastic morphology, while ICDLM cells were triangular chondrocytic in shape. This study demonstrated that the intercondylar region of the CDLM showed similar properties to the outer region of the meniscus. The inner region of the ICDLM, on the other hand, differed from the intercondylar region of the CDLM. Our results suggest that the intercondylar region of the CDLM may have a high healing potential like the outer meniscus. PMID- 27267747 TI - Comparative Analysis of the Host Response to Community-acquired and Hospital acquired Pneumonia in Critically Ill Patients. AB - RATIONALE: Preclinical studies suggest that hospitalized patients are susceptible to infections caused by nosocomial respiratory pathogens at least in part because of immune suppression caused by the condition for which they were admitted. OBJECTIVES: We aimed to characterize the systemic host response in hospital acquired pneumonia (HAP) when compared with community-acquired pneumonia (CAP). METHODS: We performed a prospective study in two intensive care units (ICUs) in 453 patients with HAP (n = 222) or CAP (n = 231). Immune responses were determined on ICU admission by measuring 19 plasma biomarkers reflecting organ systems implicated in infection pathogenesis (in 192 patients with HAP and 183 patients with CAP) and by applying genome-wide blood gene expression profiling (in 111 patients with HAP and 110 patients with CAP). MEASUREMENTS AND MAIN RESULTS: Patients with HAP and CAP presented with similar disease severities and mortality rates did not differ up to 1 year after admission. Plasma proteome analysis revealed largely similar responses, including systemic inflammatory and cytokine responses, and activation of coagulation and the vascular endothelium. The blood leukocyte genomic response was greater than 75% common in patients with HAP and CAP, comprising proinflammatory, antiinflammatory, T-cell signaling, and metabolic pathway gene sets. Patients with HAP showed overexpression of genes involved in cell-cell junction remodeling, adhesion, and diapedesis, which corresponded with lower plasma levels of matrix metalloproteinase-8 and soluble E selectin. In addition, patients with HAP demonstrated underexpression of a type-I interferon signaling gene signature. CONCLUSIONS: Patients with HAP and CAP present with a largely similar host response at ICU admission. PMID- 27267749 TI - Therapeutic options and management of polyneuropathy associated with anti-MAG antibodies. AB - INTRODUCTION: IgM monoclonal gammopathy with anti-MAG (myelin associated glycoprotein) antibodies is associated with demyelinating polyneuropathy. MAG mediates adhesion between the Schwann cell membrane (non-compact myelin) and axons. Various drugs have been tried in this form of neuropathy, with varying responses, but to date there is no consensus on the treatment of this disease. AREAS COVERED: Based on the medical literature and the experience of our group of clinicians, we offer some proposals for the management of anti-MAG neuropathy. Expert commentary: It is not certain that anti-MAG antibodies are the only factor responsible for symptoms of this clinically heterogeneous neuropathy. Some patients with mild non-evolving symptoms do not require treatment; for more severe cases, treatment should be prompt: intravenous immunoglobulins (or sometimes therapeutic plasma exchange) as first line treatment, then immunosuppressant in refractory forms (such as rituximab). PMID- 27267750 TI - Enhancing Intercellular Coordination: Rewiring Quorum Sensing Networks for Increased Protein Expression through Autonomous Induction. AB - While inducing agents are often used to redirect resources from growth and proliferation toward product outputs, they can be prohibitively expensive on the industrial scale. Previously, we developed an autonomously guided protein production system based on the rewiring of E. coli's native quorum sensing (QS) signal transduction cascade. Self-secreted autoinducer, AI-2, accumulated over time and actuated recombinant gene expression-its design, co-opting the collective nature of QS-mediated behavior. We recently demonstrated that desynchronization of autoinduced intercellular feedback leads to bimodality in QS activation. In this work, we developed a new QS-enabled system with enhanced feedback to reduce cell heterogeneity. This narrows the population distribution of protein expression, leading to significant per cell and overall increases in productivity. We believe directed engineering of cell populations and/or cell consortia will offer many such opportunities in future bioprocessing applications. PMID- 27267751 TI - Obesity and psychotropic medication: a prospective register linkage study among midlife women and men. AB - BACKGROUND: Both obesity and mental health are major public health issues. This study aimed to examine whether overweight and obesity among midlife employees are associated with subsequent psychotropic medication. A further aim was to examine the potential effect of key covariates on the association. METHODS: The Helsinki Health Study baseline survey was conducted in 2000-2002 among 40-60-year-old employees of the City of Helsinki, Finland (n = 8960). The participants were classified as of normal weight (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), obese (30-34.9 kg/m(2)) or severely obese (>=35 kg/m(2)) based on self-reported body mass index. Data on psychotropic medication purchases from baseline to 2009 were derived from registers of the Social Insurance Institution of Finland. The final analysis included 4760 women and 1338 men. Antidepressants and sedatives were examined separately. Covariates included socio-demographic factors, workload, health behaviours, physical functioning, somatic ill-health and psychotropic medication prior to baseline. Hazard ratios (HR) for the first psychotropic medication purchase were calculated using Cox regression analysis. RESULTS: Third of women and quarter of men made at least one psychotropic medication purchase during the follow-up. Adjusting for age, obese (HR = 1.57; 95 % CI = 1.10-2.24) and severely obese (HR = 2.15; 95 % CI = 1.29-3.56) men were at risk of having psychotropic medication compared to men of normal weight. These associations disappeared after further adjustment. Severe obesity remained associated with subsequent sedative medication among the men even after full adjustment (HR = 2.12; 95 % CI = 1.17-3.84). No associations were found among the women. CONCLUSIONS: Obese and severely obese men, but not women, were at risk of psychotropic medication. Further studies are needed to deepen understanding of the relationship between obesity and mental ill-health, and the possible protecting effects of age, employment, and living environment. PMID- 27267752 TI - Experimental Determination of High-Order Bending Elastic Constants of Lipid Bilayers. AB - We present a method to describe the formation of small lipid vesicles in terms of three bending elastic constants that can be experimentally measured. Our method combines a general expression of the elastic free energy of the bilayer and the thermodynamic description of molecular aggregation. The resulting model requires the size distribution of liposomes, which is determined from the X-ray scattered intensity spectra of vesicular dispersions. By using two different preparation methods, we studied a series of vesicular solutions made of distinct lipids and we obtained their corresponding bending elastic constants that are consistent with known bending rigidities. PMID- 27267754 TI - Continuous physical examination during subcortical resection in awake craniotomy patients: Its usefulness and surgical outcome. AB - OBJECTIVES: To evaluate the value of physical examination as a monitoring tool during subcortical resection in awake craniotomy patients and surgical outcomes. PATIENTS AND METHODS: Authors reviewed medical records of patients underwent awake craniotomy with continuous physical examination for pathology adjacent to the eloquent area. RESULTS: Between January 2006 and August 2015, there were 37 patients underwent awake craniotomy with continuous physical examination. Pathology was located in the left cerebral hemisphere in 28 patients (75.7%). Thirty patients (81.1%) had neuroepithelial tumors. Degree of resections were defined as total, subtotal, and partial in 16 (43.2%), 11 (29.7%) and 10 (27.0%) patients, respectively. Median follow up duration was 14 months. The reasons for termination of subcortical resection were divided into 3 groups as follows: 1) by anatomical landmark with the aid of neuronavigation in 20 patients (54%), 2) by reaching subcortical stimulation threshold in 8 patients (21.6%), and 3) by abnormal physical examination in 9 patients (24.3%). Among these 3 groups, there were statistically significant differences in the intraoperative (p=0.002) and early postoperative neurological deficit (p=0.005) with the lowest deficit in neuronavigation group. However, there were no differences in neurological outcome at later follow up (3-months p=0.103; 6-months p=0.285). There were no differences in the degree of resection among the groups. CONCLUSION: Continuous physical examination has shown to be of value as an additional layer of monitoring of subcortical white matter during resection and combining several methods may help increase the efficacy of mapping and monitoring of subcortical functions. PMID- 27267753 TI - Safety and tolerability of an anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, randomized, placebo-controlled, escalating single-dose study. AB - BACKGROUND: Systemic sclerosis (SSc) is a clinically heterogeneous, life threatening disease characterized by fibrosis, microvasculopathy, and autoimmunity. Extensive nonclinical and clinical data implicate B cells in the pathogenesis of SSc. MEDI-551 is an investigational humanized monoclonal antibody that targets the B cell surface antigen CD19 and mediates antibody-dependent, cell-mediated cytotoxicity of B cells. This clinical study evaluated the safety and tolerability, pharmacokinetics, and pharmacodynamics of MEDI-551 in subjects with SSc. METHODS: This phase I multicenter, randomized, double-blind, placebo controlled, single escalating dose study enrolled adult subjects with either limited or diffuse cutaneous SSc. A single intravenous dose of MEDI-551 was administered, and safety and tolerability were evaluated. MEDI-551 pharmacokinetics (PK), pharmacodynamics, and immunogenicity were also assessed. Safety assessments included the incidence of adverse events and changes in clinical and laboratory results. MEDI-551 serum concentrations, effects on circulating and tissue B cells and plasma cells (PCs), and antidrug antibodies were analyzed. Modified Rodnan skin score (MRSS) and pulmonary function tests were used to explore the clinical effect of MEDI-551. RESULTS: The study enrolled 28 subjects with SSc (mean age, 47.3 years; 67.9 % female). Twenty-four received a single dose of MEDI-551 (0.1-10.0 mg/kg) and four received placebo. Treatment emergent adverse events (TEAEs) occurred in 95.8 % of subjects in the MEDI-551 group and in 75.0 % of subjects in the placebo group; the majority of TEAEs were mild or moderate in severity. Two serious adverse events were considered possibly related to the study drug. One death, deemed not related to the study drug, occurred in a MEDI-551-treated subject. MEDI-551 exhibited linear PK in the dose range of 1.0 to 10.0 mg/kg, and more rapid clearance at lower doses. Dose dependent depletion of circulating B cells and plasma cells was observed. MRSS assessments suggest a possible clinical effect of MEDI-551 on affected skin. CONCLUSIONS: A single escalating dose of MEDI-551 was tolerable and safe in this subject population. B cell depletion was achieved and was dose dependent. A signal of clinical effect was observed. Based on these results, further investigation of MEDI-551 as a disease-modifying treatment for SSc is warranted. TRIAL REGISTRATION: www.clinicaltrials.gov identifier, NCT00946699 ; registered 23 July 2009. PMID- 27267755 TI - The PLE(2)NO self-management and exercise program for knee osteoarthritis: Study Protocol for a Randomized Controlled Trial. AB - BACKGROUND: International recommendations suggest exercise and self-management programs, including non-pharmacological treatments, for knee osteoarthritis (KOA) because they can benefit pain relief and improve function and exercise adherence. The implementation of a combined self-management and exercise program termed PLE(2)NO may be a good method for controlling KOA symptoms because it encourages the development of self-efficacy to manage the pathology. This study will assess the effects of a self-management and exercise program in comparison to an educational intervention (control program) on symptoms, physical fitness, health related quality of life, self-management behaviors, self-efficacy, physical activity level and coping strategies. METHODS/DESIGN: This PLE(2)NO study is a single-blinded, randomized controlled trial of elderly (aged above 60 yrs old) patients with clinical and radiographic KOA. The patients will be allocated into either an educational group (control) or a self-management and exercise group (experimental). All participants will receive a supplement of chondroitin and glucosamine sulfates. This paper describes the protocol that will be used in the PLE(2)NO program. DISCUSSION: This program has several strengths. First, it involves a combination of self-management and exercise approaches, is available in close proximity to the patients and occurs over a short period of time. The latter two characteristics are crucial for maintaining participant adherence. Exercise components will be implemented using low-cost resources that permit their widespread application. Moreover, the program will provide guidance regarding the effectiveness of using a self-management and exercise program to control KOA symptoms and improve self-efficacy and health-related quality of life. TRIAL REGISTRATION: NCT02562833 (09/23/2015). PMID- 27267756 TI - Co-infection of a hypovirulent isolate of Sclerotinia sclerotiorum with a new botybirnavirus and a strain of a mitovirus. AB - BACKGROUND: Sclerotinia sclerotiorum, a notorious plant fungal pathogen, causes yield loss of many crops and vegetables, and is a natural host of a diverse viruses with positive-sense RNA (+ssRNA), negative-sense RNA (-ssRNA), double stranded RNA (dsRNA), or DNA genomes. Mixed-infection with multiple related or unrelated mycoviruses is a common phenomenon in S. sclerotiorum. However, a single strain co-infected with dsRNA and + ssRNA viruses has not been reported in S. sclerotiorum. RESULTS: We report two unrelated viruses, Sclerotinia sclerotiorum botybirnavirus 2 (SsBRV2) with a bipartite dsRNA genome and Sclerotinia sclerotiorum mitovirus 4 (SsMV4/AH16) with a + ssRNA genome, which were originally detected in a single hypovirulent strain AH16 of S. sclerotiorum. SsMV4/AH16 has a typical genome of mitovirus and is a strain of mitovirus SsMV4. The genome of SsBRV2 consists of two separated dsRNA segments. The large dsRNA segment is 6159 bp in length and only has a single open reading frame (ORF) encoding a putative 1868-aa polyprotein with a conserved RNA dependent RNA polymerase (RdRp) domain. The small dsRNA segment is 5872 bp in length and encodes a putative 1778-aa protein. Phylogenetic analysis using RdRp conserved domain sequences revealed that SsBRV2 is phylogenetically related to the previously reported three bipartite viruses SsBRV1, Botrytis porri RNA virus 1 (BpRV1), and soybean leaf-associated botybirnavirus 1 (SlaBRV1). Electron microscopy demonstrated that SsBRV2 forms rigid spherical virions with a diameter of approximately 40 nm in infected mycelia. The virion of SsBRV2 was successfully introduced into a virus-free strain, which provides conclusive evidence that SsBRV2 confers hypovirulence on phytopathogenic fungus S. sclerotiorum. CONCLUSIONS: A bisegmented dsRNA virus (SsBRV2/AH16) and a nonsegmented + ssRNA virus (SsMV4/AH16) were characterized in a hypovirulent strain AH16 of S. sclerotiorum. SsMV4/AH16 is a strain of a reported mitovirus, whereas SsBRV2 is a new botybirnavirus. SsBRV2 is the causal agent of hypovirulence on S. sclerotiorum. Our findings supplied a first evidence that a single S. sclerotiorum strain is co-infected by dsRNA and + ssRNA mycoviruses. PMID- 27267757 TI - Sub-Saharan red cell antigen phenotypes and glucose-6-phosphate dehydrogenase deficiency variants in French Guiana. AB - BACKGROUND: The treatment of Plasmodium vivax infections requires the use of primaquine, which can lead to severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. However, most of the Latin American countries, which are still endemic for vivax malaria, lack information on the distribution of G6PD deficiency (G6PDd). No survey has been performed so far in French Guiana. Herein, 80 individuals of the French Guianan Noir Marron population were scrutinized for red cell surface antigens of six blood group systems (ABO, Rh, Kell, Kidd, Duffy and MNS) and G6PD genetic polymorphisms. First, the sub-Saharan origin of the red cell phenotypes was assessed in relation with the literature. Then, given that the main sub-Saharan G6PDd variants are expected to be encountered, only the G6PD sequences of exons 4, 5, 6 and 9 were screened. This work aims at appraising the G6PD gene variation in this population, and thus, contributing to the G6PD piecemeal information in Latin America. RESULTS: Ninety-seven percent (97 %) of the red cells are Fy(a- b-), either D+ C- E- c+ e+ or D+ C+ E- c+ e+ and 44 % exhibited the Fya-/Jkb-/S- combined phenotype. Noteworthy is the detection of the G6PD(Val68Met) variant characterized by c.202G > A transition, G6PD(Asn126Asp) variant characterized by c.376A>G transition and G6PD(Asp181Val) variant characterized by c.542A>T transversion of the G6PD gene in 22.5 % of the sample, characteristic of the A( (202)), A and Santamaria G6PDd variants, respectively. CONCLUSIONS: French Guianan Noir Marron population represents a pool of Rh-D antigen positive, Duffy negative and G6PD-deficient erythrocytes, the latter accounting for one in every eight persons. The present study provides the first community-based estimation of the frequency of G6PDd polymorphisms in French Guiana. These results contribute to the G6PD genetic background information puzzle in Latin America. PMID- 27267758 TI - Comparison of abnormal isoform of prion protein in prion-infected cell lines and primary-cultured neurons by PrPSc-specific immunostaining. AB - We established abnormal isoform of prion protein (PrPSc)-specific double immunostaining using mAb 132, which recognizes aa 119-127 of the PrP molecule, and novel PrPSc-specific mAb 8D5, which recognizes the N-terminal region of the PrP molecule. Using the PrPSc-specific double immunostaining, we analysed PrPSc in immortalized neuronal cell lines and primary cerebral-neuronal cultures infected with prions. The PrPSc-specific double immunostaining showed the existence of PrPSc positive for both mAbs 132 and 8D5, as well as those positive only for either mAb 132 or mAb 8D5. This indicated that double immunostaining detects a greater number of PrPSc species than single immunostaining. Double immunostaining revealed cell-type-dependent differences in PrPSc staining patterns. In the 22 L prion strain-infected Neuro2a (N2a)-3 cells, a subclone of N2a neuroblastoma cell line, or GT1-7, a subclone of the GT1 hypothalamic neuronal cell line, granular PrPSc stains were observed at the perinuclear regions and cytoplasm, whereas unique string-like PrPSc stains were predominantly observed on the surface of the 22 L strain-infected primary cerebral neurons. Only 14 % of PrPSc in the 22 L strain-infected N2a-3 cells were positive for mAb 8D5, indicating that most of the PrPSc in N2a-3 lack the N-terminal portion. In contrast, nearly half PrPSc detected in the 22 L strain-infected primary cerebral neurons were positive for mAb 8D5, suggesting the abundance of full-length PrPSc that possesses the N-terminal portion of PrP. Further analysis of prion-infected primary neurons using PrPSc-specific immunostaining will reveal the neuron specific mechanism for prion propagation. PMID- 27267759 TI - Microvascular endothelial cells-derived microvesicles imply in ischemic stroke by modulating astrocyte and blood brain barrier function and cerebral blood flow. AB - BACKGROUND: Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage. RESULTS: EMVs prepared from ECs cultured in normal condition (n-EMVs) or oxygen and glucose deprivation (OGD-EMVs) condition had diverse effects on astrocytes. The n-EMVs promoted, while the OGD-EMVs inhibited the proliferation of astrocytes via regulating PI3K/Akt pathway. Glial fibrillary acidic protein (GFAP) expression (marker of astrocyte activation) was up regulated by n-EMVs, while down-regulated by OGD-EMVs. Meanwhile, n-EMVs inhibited but OGD-EMVs promoted the apoptosis of astrocytes accompanied by up/down-regulating the expression of Caspase-9 and Bcl-2. In the BBB model of ECs astrocytes co-culture, the n-EMVs, conversely to OGD-EMVs, decreased the permeability of BBB accompanied with up-regulation of zonula occudens-1(ZO-1) and Claudin-5. In a transient cerebral ischemia mouse model, n-EMVs ameliorated, while OGD-EMVs aggravated, BBB disruption, local cerebral blood flow (CBF) reduction, infarct volume and neurological deficit score. CONCLUSIONS: Our data suggest that EMVs diversely modulate astrocyte functions, BBB integrity and CBF, and could serve as a novel therapeutic target for ischemic stroke. PMID- 27267760 TI - Association mapping for cold tolerance in two large maize inbred panels. AB - BACKGROUND: Breeding for cold tolerance in maize promises to allow increasing growth area and production in temperate zones. The objective of this research was to conduct genome-wide association analyses (GWAS) in temperate maize inbred lines and to find strategies for pyramiding genes for cold tolerance. Two panels of 306 dent and 292 European flint maize inbred lines were evaluated per se and in testcrosses under cold and control conditions in a growth chamber. We recorded indirect measures for cold tolerance as the traits number of days from sowing to emergence, relative leaf chlorophyll content or quantum efficiency of photosystem II. Association mapping for identifying genes associated to cold tolerance in both panels was based on genotyping with 49,585 genome-wide single nucleotide polymorphism (SNP) markers. RESULTS: We found 275 significant associations, most of them in the inbreds evaluated per se, in the flint panel, and under control conditions. A few candidate genes coincided between the current research and previous reports. A total of 47 flint inbreds harbored the favorable alleles for six significant quantitative trait loci (QTL) detected for inbreds per se evaluated under cold conditions, four of them had also the favorable alleles for the main QTL detected from the testcrosses. Only four dent inbreds (EZ47, F924, NK807 and PHJ40) harbored the favorable alleles for three main QTL detected from the evaluation of the dent inbreds per se under cold conditions. There were more QTL in the flint panel and most of the QTL were associated with days to emergence and PhiPSII. CONCLUSIONS: These results open new possibilities to genetically improve cold tolerance either with genome-wide selection or with marker assisted selection. PMID- 27267761 TI - Comparing the performance of the EQ-5D-3L and the EQ-5D-5L in young Portuguese adults. AB - BACKGROUND: Some studies have reported a ceiling effect in EQ-5D-3L, especially in healthy and/or young individuals. Recently, two further levels have been included in its measurement model (EQ-5D-5L). The purposes of this study were (1) to assess the properties of the EQ-5D-5L in comparison with the standard EQ-5D-3L in a sample of young adults, (2) to foreground the importance of collecting qualitative data to confirm, validate or refine the EQ-5D questionnaire items and (3) to raise questions pertaining to the wording in these questionnaire items. METHODS: The data used came from a sample of respondents aged 30 or under (n = 624). They completed both versions of the EQ-5D, which were compared in terms of feasibility, level of inconsistency and ceiling effect. Agreement between the instruments was assessed using correlation coefficients and Bland-Altman plots. Known-groups validity of the EQ-5D-5L was also assessed using non-parametric tests. The discriminative properties were compared using receiver operating characteristic curves. Finally, four interviews were conducted for retrospective reports to elicit respondents' understanding and perceptions of the format, instructions, items, and responses. RESULTS: Quantitative results show a ceiling effect reduction of 25.3 % and a high level agreement between both indices. Known groups validity was confirmed for the EQ-5D-5L. Explorative interviews indicated ambiguity and low degree of certainty in regards to conceptualizing differences between levels moderate-slight across three dimensions. CONCLUSIONS: The EQ-5D-5L performed better than the EQ-5D-3L. However, the explorative interviews demonstrated several limitations in the EQ-5D questionnaire wording and high context-dependent answers point to lack of illnesses' experience amongst young adults. PMID- 27267762 TI - Electrolyte disturbances and risk factors of acute kidney injury patients receiving dialysis in exertional heat stroke. AB - BACKGROUND: Exertional heat stroke (EHS) is a life-threatening illness and leads to multi-organ dysfunction including acute kidney injury (AKI). The clinical significance of abnormal electrolytes and renal outcomes in ESH patients has been poorly documented. We aim to exhibit the electrolyte abnormalities, renal outcomes and risk factors of patients with AKI receiving dialysis in EHS. METHODS: A retrospective cohort study in EHS patients between 2003 and 2014 were conducted. Clinical and laboratory outcomes including serum and urine electrolytes, AKI and dialysis were assessed on admission, during hospitalization and at the time of their discharge from the hospital. A logistic regression analysis was performed for risk factors of acute dialysis. RESULTS: All 66 subjects with mean age 22.1 +/- 4.3 years were included. On admission, the common electrolyte disturbances were hypokalemia (71.2 %), hypophosphatemia (59.1 %), hyponatremia (53.0 %), hypocalcemia (51.5 %), and hypomagnesemia (34.9 %). Electrolytes depletion was confirmed as renal loss (potassium loss; 54.2 %, phosphate loss; 86.7 %, sodium loss; 64.7 % and magnesium loss; 83.3 %). During hospitalization ranging from 2 to 209 days, 90.9 % patients suffered from AKI with 16.7 % receiving acute dialysis, and 3 % patients died. At discharge, AKI and electrolyte abnormalities had dramatically improved. The prognosis factors for AKI receiving dialysis were identified as neurological status, renal function and serum muscle enzyme at time of admission. CONCLUSION: The study suggests that hypoelectrolytemia and AKI are frequently observed in patients with EHS. Neurological impairment, impaired renal function, and increased serum muscle enzyme should be considered risk factors of acute dialysis. PMID- 27267763 TI - How do general practitioners contribute to preventing long-term work disability of their patients suffering from depressive disorders? A qualitative study. AB - BACKGROUND: Depression is a major cause of work absenteeism that general practitioners (GPs) face directly since they are responsible for sickness certification and for supervising the return to work (RTW). These activities give GPs a key role in preventing long-term work disability, yet their practices in this regard remain poorly documented. The objectives of this study were therefore to describe GPs' practices with people experiencing work disability due to depressive disorders and explore how GPs' work context may impact on their practices. METHODS: We conducted semi-structured individual interviews with 13 GPs and six mental healthcare professionals in two sub-regions of Quebec. The sub regions differed in terms of availability of specialized resources offering public mental health services. Data were anonymized and transcribed verbatim. Thematic analysis was performed to identify patterns in the GPs' practices and highlight impacting factors in their work context. RESULTS: Our results identified a set of practices common to all the GPs and other practices that differentiated them. Two profiles were defined on the basis of the various practices documented. The first is characterized by the integration of the RTW goal into the treatment goal right from sickness certification and by interventions that include the workplace, albeit indirectly. The second is characterized by a lack of early RTW-oriented action and by interventions that include little workplace involvement. Regardless of the practice profile, actions intended to improve collaboration with key stakeholders remain the exception. However, two characteristics of the work context appear to have an impact: the availability of a dedicated mental health nurse and the regular provision of clinical information by psychotherapists. These conditions are rarely present but tend to make a significant difference for the GPs. CONCLUSIONS: Our results highlight the significant role of GPs in the prevention of long-term work disability and their need for support through the organization of mental health services at the primary care level. PMID- 27267767 TI - Former medical director faces claims that he failed to act over concerns about doctor. PMID- 27267765 TI - Domains of quality for clinical ethics case consultation: a mixed-method systematic review. AB - BACKGROUND: "Clinical ethics consultation" (CEC) is the provision of consultative services by an individual or team with the aim of helping health professionals, patients, and their families grapple with difficult ethical issues arising during health care. There are almost 25,000 articles in the worldwide literature on CEC, but very few explicitly address measuring the quality of CEC. Many more address quality implicitly, however. This article describes a rigorous protocol for compiling the diverse literature on CEC, analyzing it with a quality measurement lens, and seeking a set of potential quality domains for CEC based on areas of existing, but hitherto unrecognized, consensus in the literature. METHODS/DESIGN: This mixed-method systematic review will follow a sequential pattern: scoping review, qualitative synthesis, and then a quantitative synthesis. The scoping review will include categorizing all quality measures for CEC discussed in the literature, both quantitative and qualitative. The qualitative synthesis will generate a comprehensive analytic framework for understanding the quality of CEC and is expected to inform the quantitative synthesis, which will be a meta analysis of studies reporting the effects of CEC on pre-specified clinical outcomes. DISCUSSION: The literature on CEC is broad and diverse and has never been examined with specific regard to quality measurement. We propose a novel mixed-methods approach to compile and synthesize this literature and to derive a framework for assessing quality in CEC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023282. PMID- 27267764 TI - Autoinflammatory Skin Disorders: The Inflammasomme in Focus. AB - Autoinflammatory skin disorders are a group of heterogeneous diseases that include diseases such as cryopyrin-associated periodic syndrome (CAPS) and familial Mediterranean fever (FMF). Therapeutic strategies targeting IL-1 cytokines have proved helpful in ameliorating some of these diseases. While inflammasomes are the major regulators of IL-1 cytokines, inflammasome independent complexes can also process IL-1 cytokines. Herein, we focus on recent advances in our understanding of how IL-1 cytokines, stemming from inflammasome dependent and -independent pathways are involved in the regulation of skin conditions. Importantly, we discuss several mouse models of skin inflammation generated to help elucidate the basic cellular and molecular effects and modulation of IL-1 in the skin. Such models offer perspectives on how these signaling pathways could be targeted to improve therapeutic approaches in the treatment of these rare and debilitating inflammatory skin disorders. PMID- 27267766 TI - Common pathway signature in lung and liver fibrosis. AB - Fibrosis, a progressive accumulation of extracellular matrix components, encompasses a wide spectrum of distinct organs, and accounts for an increasing burden of morbidity and mortality worldwide. Despite the tremendous clinical impact, the mechanisms governing the fibrotic process are not yet understood, and to date, no clinically reliable therapies for fibrosis have been discovered. Here we applied Regeneration Intelligence, a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in lung and liver fibrosis. In both tissues, our analysis detected major conserved signaling pathways strongly associated with fibrosis, suggesting that some of the pathways identified by our algorithm but not yet wet-lab validated as fibrogenesis related, may be attractive targets for future research. While the majority of significantly disrupted pathways were specific to histologically distinct organs, several pathways have been concurrently activated or downregulated among the hepatic and pulmonary fibrosis samples, providing new evidence of evolutionary conserved pathways that may be relevant as possible therapeutic targets. While future confirmatory studies are warranted to validate these observations, our platform proposes a promising new approach for detecting fibrosis-promoting pathways and tailoring the right therapy to prevent fibrogenesis. PMID- 27267768 TI - Temporal bone radiology report classification using open source machine learning and natural langue processing libraries. AB - BACKGROUND: Radiology reports are a rich resource for biomedical research. Prior to utilization, trained experts must manually review reports to identify discrete outcomes. The Audiological and Genetic Database (AudGenDB) is a public, de identified research database that contains over 16,000 radiology reports. Because the reports are unlabeled, it is difficult to select those with specific abnormalities. We implemented a classification pipeline using a human-in-the-loop machine learning approach and open source libraries to label the reports with one or more of four abnormality region labels: inner, middle, outer, and mastoid, indicating the presence of an abnormality in the specified ear region. METHODS: Trained abstractors labeled radiology reports taken from AudGenDB to form a gold standard. These were split into training (80 %) and test (20 %) sets. We applied open source libraries to normalize and convert every report to an n-gram feature vector. We trained logistic regression, support vector machine (linear and Gaussian), decision tree, random forest, and naive Bayes models for each ear region. The models were evaluated on the hold-out test set. RESULTS: Our gold standard data set contained 726 reports. The best classifiers were linear support vector machine for inner and outer ear, logistic regression for middle ear, and decision tree for mastoid. Classifier test set accuracy was 90 %, 90 %, 93 %, and 82 % for the inner, middle, outer and mastoid regions, respectively. The logistic regression method was very consistent, achieving accuracy scores within 2.75 % of the best classifier across regions and a receiver operator characteristic area under the curve of 0.92 or greater across all regions. CONCLUSIONS: Our results indicate that the applied methods achieve accuracy scores sufficient to support our objective of extracting discrete features from radiology reports to enhance cohort identification in AudGenDB. The models described here are available in several free, open source libraries that make them more accessible and simplify their utilization as demonstrated in this work. We additionally implemented the models as a web service that accepts radiology report text in an HTTP request and provides the predicted region labels. This service has been used to label the reports in AudGenDB and is freely available. PMID- 27267769 TI - Two-Way Radio Modem Data Transfer for Newborn Hearing Screening Devices. AB - INTRODUCTION: The success of a newborn hearing screening program depends on successful tracking and follow-up to ensure that children who have had positive screening results in the first few days of life receive appropriate and timely diagnostic and intervention services. The easy availability, through a suitable infrastructure, of the data necessary for the tracking, diagnosis, and care of children concerned is a major key to enhancing the quality and efficiency of newborn hearing screening programs. MATERIALS AND METHODS: Two systems for the automated two-way transmission of newborn hearing screening and configuration data, based on mobile communication technology, for the screening devices MADSEN AccuScreen(r) and Natus Echo-Screen(r) were developed and tested in a field study. Radio modem connections were compared with conventional analogue modem transmissions from Natus Echo-Screen devices for duration, transmission rate, number of lost connections, and frequency of use. RESULTS: The average session duration was significantly lower with the MADSEN AccuScreen (12 s) and Natus Echo Screen both with radio modem (15 s) than the Natus Echo-Screen with analogue modem (108 s). The transmission rate was significantly higher (898 and 1,758 vs. 181 bytes/s) for the devices with radio modems. Both radio modem devices had significantly lower rates of broken connections after initial connection (2.1 and 0.9 vs. 5.5%). An increase in the frequency of data transmission from the clinics with mobile radio devices was found. CONCLUSIONS: The use of mobile communication technology in newborn hearing screening devices offers improvements in the average session duration, transmission rate, and reliability of the connection over analogue solutions. We observed a behavioral change in clinical staff using the new technology: the data exchange with the tracking center is more often used. The requirements for on-site support were reduced. These savings outweigh the small increase in costs for the Internet service provider. PMID- 27267770 TI - Hip kinetics during gait are clinically meaningful outcomes in young boys with Duchenne muscular dystrophy. AB - Duchenne muscular dystrophy (DMD) is an X-linked genetic neuromuscular disorder characterized by progressive proximal to distal muscle weakness. The success of randomized clinical trials for novel therapeutics depends on outcome measurements that are sensitive to change. As the development of motor skills may lead to functional improvements in young boys with DMD, their inclusion may potentially confound clinical trials. Three-dimensional gait analysis is an under-utilized approach that can quantify joint moments and powers, which reflect functional muscle strength. In this study, gait kinetics, kinematics, spatial-temporal parameters, and timed functional tests were quantified over a one-year period for 21 boys between 4 and 8 years old who were enrolled in a multisite natural history study. At baseline, hip moments and powers were inadequate. Between the two visits, 12 boys began a corticosteroid regimen (mean duration 10.8+/-2.4 months) while 9 boys remained steroid-naive. Significant between-group differences favoring steroid use were found for primary kinetic outcomes (peak hip extensor moments (p=.007), duration of hip extensor moments (p=.007), peak hip power generation (p=.028)), and spatial-temporal parameters (walking speed (p=.016) and cadence (p=.021)). Significant between-group differences were not found for kinematics or timed functional tests with the exception of the 10m walk test (p=.03), which improves in typically developing children within this age range. These results indicate that hip joint kinetics can be used to identify weakness in young boys with DMD and are sensitive to corticosteroid intervention. Inclusion of gait analysis may enhance detection of a treatment effect in clinical trials particularly for young boys with more preserved muscle function. PMID- 27267771 TI - The effect of proprioceptive knee bracing on knee stability during three different sport related movement tasks in healthy subjects and the implications to the management of Anterior Cruciate Ligament (ACL) injuries. AB - INTRODUCTION: Proprioceptive knee braces have been shown to improve knee mechanics, however much of the work to date has focused on tasks such as slow step down tasks rather than more dynamic sporting tasks. OBJECTIVE: This study aimed to explore if such improvements in stability may be seen during faster sports specific tasks as well as slower tasks. METHOD: Twelve subjects performed a slow step down, single leg drop jump and pivot turn jump with and without a silicone web brace. 3D kinematics of the knee were collected using a ten camera Qualisys motion analysis system. Reflective markers were placed on the foot, shank, thigh and pelvis using the Calibrated Anatomical Systems Technique. A two way ANOVA with repeated measures was performed with post-hoc pairwise comparison to explore the differences between the two conditions and three tasks. RESULTS: Significant differences were seen in the knee joint angles and angular velocities in the sagittal, coronal and transverse planes between the tasks. The brace showed a reduction in knee valgum and internal rotation across all tasks, with the most notable effect during the single leg drop jump and pivot turn jump. The transverse plane also showed a significant reduction in the external rotation knee angular velocity when wearing the brace. DISCUSSION: The brace influenced the knee joint kinematics in coronal and transverse planes which confirms that such braces can have a significant effect on knee control during dynamic tasks. Further studies are required exploring the efficacy of proprioceptive braces in athletic patient cohort. PMID- 27267772 TI - Author's reply. PMID- 27267773 TI - Retropneumoperitoneum due to fulminant spondylodiscitis. PMID- 27267774 TI - Sepsis biomarkers in severe burn patients: Cut-off point or time profile? PMID- 27267776 TI - Learning Microbial Interaction Networks from Metagenomic Count Data. AB - Many microbes associate with higher eukaryotes and impact their vitality. To engineer microbiomes for host benefit, we must understand the rules of community assembly and maintenance that, in large part, demand an understanding of the direct interactions among community members. Toward this end, we have developed a Poisson-multivariate normal hierarchical model to learn direct interactions from the count-based output of standard metagenomics sequencing experiments. Our model controls for confounding predictors at the Poisson layer and captures direct taxon-taxon interactions at the multivariate normal layer using an l1 penalized precision matrix. We show in a synthetic experiment that our method handily outperforms state-of-the-art methods such as SparCC and the graphical lasso (glasso). In a real in planta perturbation experiment of a nine-member bacterial community, we show our model, but not SparCC or glasso, correctly resolves a direct interaction structure among three community members that associates with Arabidopsis thaliana roots. We conclude that our method provides a structured, accurate, and distributionally reasonable way of modeling correlated count-based random variables and capturing direct interactions among them. PMID- 27267775 TI - Deconvolution of Ensemble Chromatin Interaction Data Reveals the Latent Mixing Structures in Cell Subpopulations. AB - Chromosome conformation capture (3C) experiments provide a window into the spatial packing of a genome in three dimensions within the cell. This structure has been shown to be correlated with gene regulation, cancer mutations, and other genomic functions. However, 3C provides mixed measurements on a population of typically millions of cells, each with a different genome structure due to the fluidity of the genome and differing cell states. Here, we present several algorithms to deconvolve these measured 3C matrices into estimations of the contact matrices for each subpopulation of cells and relative densities of each subpopulation. We formulate the problem as that of choosing matrices and densities that minimize the Frobenius distance between the observed 3C matrix and the weighted sum of the estimated subpopulation matrices. Results on HeLa 5C and mouse and bacteria Hi-C data demonstrate the methods' effectiveness. We also show that domain boundaries from deconvolved matrices are often more enriched or depleted for regulatory chromatin markers when compared to boundaries from convolved matrices. PMID- 27267777 TI - Global and Targeted Metabolomics Evidence of the Protective Effect of Chinese Patent Medicine Jinkui Shenqi Pill on Adrenal Insufficiency after Acute Glucocorticoid Withdrawal in Rats. AB - Glucocorticoids are commonly used in anti-inflammatory and immunomodulatory therapies, but glucocorticoid withdrawal can result in life-threatening risk of adrenal insufficiency. Chinese patented pharmaceutical product Jinkui Shenqi pill (JKSQ) has potent efficacy on clinical adrenal insufficiency resulting from glucocorticoid withdrawal. However, the underlying molecular mechanism remains unclear. We used an animal model to study JKSQ-induced metabolic changes under adrenal insufficiency and healthy conditions. Sprague-Dawley rats were treated with hydrocortisone for 7 days with or without 15 days of JKSQ pretreatment. Sera were collected after 72 h hydrocortisone withdrawal and used for global and free fatty acids (FFAs)-targeted metabolomics analyses using gas chromatography/time of-flight mass spectrometry and ultraperformance liquid chromatography/quadruple time-of-flight mass spectrometry. Rats without hydrocortisone treatment were used as controls. JKSQ pretreatment normalized the significant changes of 13 serum metabolites in hydrocortisone-withdrawal rats, involving carbohydrates, lipids, and amino acids. The most prominent effect of JKSQ was on the changes of FFAs and some [product FFA]/[precursor FFA] ratios, which represent estimated desaturase and elongase activities. The opposite metabolic responses of JKSQ in adrenal insufficiency rats and normal rats highlighted the "Bian Zheng Lun Zhi" (treatment based on ZHENG differentiation) guideline of TCM and suggested that altered fatty acid metabolism was associated with adrenal insufficiency after glucocorticoid withdrawal and the protective effects of JKSQ. PMID- 27267779 TI - Prevalence of sorbitol non-fermenting Shiga toxin-producing Escherichia coli in Black Bengal goats on smallholdings. AB - A cross-sectional survey was carried out in Bangladesh with the sampling of 514 Black Bengal goats on smallholdings to determine the presence of sorbitol non fermenting (SNF) Shiga toxin-producing E. coli (STEC). Swab samples collected from the recto-anal junction were plated onto cefixime and potassium tellurite added sorbitol MacConkey (CT-SMAC) agar, a selective medium for STEC O157 serogroup, where this serogroup and other SNF STEC produce colourless colonies. The SNF E. coli (SNF EC) isolates obtained from the survey were investigated by PCR for the presence of Shiga toxin-producing genes, stx1 and stx2, and two other virulence genes, eae and hlyA that code for adherence factor (intimin protein) and pore-forming cytolysin, respectively. The SNF EC isolates were also assessed for the presence of the rfbO157 gene to verify their identity to O157 serogroup. The results revealed that the proportions of goats carrying SNF EC isolates and stx1 and stx2 genes were 6.2% (32/514) [95% confidence interval (CI) 4.4-8.7)], 1.2% (95% CI 0.5-2.6) and 1.2% (95% CI 0.5-2.6), respectively. All the SNF STEC tested negative for rfbO157, hlyA and eae genes. The risk for transmission of STEC from Black Bengal goats to humans is low. PMID- 27267778 TI - Cross-talk between 4-1BB and TLR1-TLR2 Signaling in CD8+ T Cells Regulates TLR2's Costimulatory Effects. AB - The activation of TLR-MyD88 (Toll-like receptor-myeloid differentiation factor 88) signaling within T cells functions as a potent costimulatory signal that boosts antitumor and antiviral responses. However, the molecular mechanisms underlying the costimulatory processes are poorly understood. We compared microarray gene analysis data between TLR1-TLR2-stimulated and unstimulated T cell receptor transgenic "pmel" and MyD88(-/-) pmel CD8(+) T cells and identified changes in the expression of several TNF family members. In particular, TLR stimulation increased 4-1BB levels in pmel but not in MyD88(-/-)pmel T cells. A link between 4-1BB and TLR1-TLR2 signaling in CD8(+) T cells was highlighted by the suboptimal responses of 4-1BB(-/-) T cells to TLR1-TLR2 agonist, but their normal response to CD28 or OX40 costimulation. Blocking 4-1BB signaling with antibodies also hindered the costimulatory effects of the TLR1-TLR2 agonist. The elevated levels of 4-1BB transcripts in TLR1-TLR2-stimulated cells were not due to increased mRNA stability nor increased histone activation, but instead were associated with increased binding of p65 and c-Jun to two distinct 4-1BB promoter sites. Combining TLR1-TLR2 ligand with an agonistic antibody to 4-1BB enhanced the antitumor activity in mice with established melanoma tumors. These studies reveal that the costimulatory effects of TLR1-TLR2 signaling in CD8(+) T cells are in part mediated by 4-1BB and are important for mounting an effective antitumor immune response. Cancer Immunol Res; 4(8); 708-16. (c)2016 AACR. PMID- 27267780 TI - BK Virus in Kidney Transplant: Current Concepts, Recent Advances, and Future Directions. AB - BK virus nephropathy is a challenging clinical problem in kidney transplant recipients with wide range of surveillance and management practices, based on individual experience. BK virus reactivation in kidney transplant recipients can result in BK virus nephropathy and graft loss. The most effective strategy for early diagnosis and treatment of BK virus nephropathy is regular monitoring for BK virus, currently achieved by quantification of viral DNA in blood by quantitative polymerase chain reaction. Immunosuppression reduction remains the mainstay of treatment; however, viral clearance is often followed by acute rejection, likely secondary to a delay between immune reconstitution and viral clearance. Impaired cell-mediated immune response to BK virus has been shown to correlate with progression to BK virus nephropathy, while reconstitution of this response correlates with resolution of nephropathy. There is recent research to support monitoring BK virus-specific cell-mediated immune response as a predictor of disease progression and resolution. In this article, we review the current concepts and recent developments in understanding BK virus-associated disease in the context of kidney transplant and outline areas for future research. PMID- 27267781 TI - Well-defined reducible cationic nanogels based on functionalized low-molecular weight PGMA for effective pDNA and siRNA delivery. AB - Nucleic acid-based gene therapy is a promising treatment option to cure numerous intractable diseases. For non-viral gene carriers, low-molecular-weight polymeric vectors generally demonstrate poor transfection performance, but benefit their final removals from the body. Recently, it was reported that aminated poly(glycidyl methacrylate) (PGMA) is one potential gene vector. Based on ethylenediamine (ED)-functionalized low-molecular-weight PGMA (denoted by PGED), a flexible strategy was herein proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with friendly crosslinking reagents for highly efficient nucleic acid delivery. alpha-Lipoic acid (LA), one natural antioxidant in human body, was readily introduced into ED-functionalized PGMA and crosslinked to produce cationic PGED-NGs with plentiful reducible lipoyl groups. PGED-NGs could effectively complex plasmid DNA (pDNA) and short interfering RNA (siRNA). Compared with pristine PGED, PGED-NGs exhibited much better performance of pDNA transfection. PGED-NGs also could efficiently transport MALAT1 siRNA (siR M) into hepatoma cells and significantly suppressed the cancer cell proliferation and migration. The present work indicated that reducible cationic nanogels involving LA crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems. STATEMENT OF SIGNIFICANCE: Recently, the design of new types of high-performance nanoparticles is of great significance in delivering therapeutics. Nucleic acid-based therapy is a promising treatment option to cure numerous intractable diseases. A facile and straightforward strategy to fabricate safe nucleic acid delivery nanovectors is highly desirable. In this work, based on ethylenediamine-functionalized low molecular-weight poly(glycidyl methacrylate), a flexible strategy was proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with alpha-Lipoic acid, one friendly crosslinking reagent, for highly efficient nucleic acid delivery. Such PGED-NGs possess plentiful reducible lipoyl groups, effectively encapsulated pDNA and siRNA and exhibited excellent abilities of nucleic acid delivery. The present work indicated that reducible cationic nanogels involving alpha-lipoic acid crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems. PMID- 27267782 TI - Preferred Features of E-Mental Health Programs for Prevention of Major Depression in Male Workers: Results From a Canadian National Survey. AB - BACKGROUND: Major depression is a prevalent mental disorder and imposes considerable burden on health and productivity. Men are not immune to major depression, yet they often delay seeking help because of perceived stigma and gender norms. E-mental health programs hold potential for early prevention of major depression. However, we have little knowledge about men's preferences for design features of e-mental health programs. OBJECTIVES: The objective of this study was to (1) estimate and compare the proportions of Internet use for medical information, preferred design features, and likely use of e-mental health programs; (2) examine factors associated with the likely use of e-mental health programs; and (3) understand potential barriers to the use of e-mental health programs among Canadian working men, who were at high risk of a major depressive episode (MDE). METHODS: A cross-sectional survey in 10 Canadian provinces was conducted between March and December 2015. Random digit dialing method was used through household landlines and cell phones to collect data from 511 working men who were at high risk of having an MDE and 330 working men who were at low risk of having an MDE. RESULTS: High-risk men were more likely to endorse the importance of accessing health resources on the Internet than low-risk men (83.4% vs 75.0%, respectively; P=.01). Of the 17 different features assessed, the top three features most likely to be used by high-risk men were: "information about improving sleep hygiene" (61.3%), "practice and exercise to help reduce symptoms of stress and depression" (59.5%), and "having access to quality information and resources about work stress issues" (57.8%). Compared with men at low risk for MDE, men at high risk for MDE were much more likely to consider using almost every one of the different design features. Differences in preferences for the design features by age among men at high risk of MDE were found only for 3 of 17 features. Differences in preferences for design features between English- and French-speaking participants were found only for 4 out of the 17 features. Analysis of qualitative data revealed that privacy issues, perceived stigma, ease of navigation, personal relevance, and lack of personal interaction, time, and knowledge were identified as barriers to the use of e-mental health programs in working men who were at high risk of MDE. CONCLUSION: E-mental health programs may be a promising strategy for prevention of depression in working men. Development of e-mental health programs should consider men's preferences and perceived barriers to enhance the acceptability of this approach. PMID- 27267783 TI - Identifying frailty risk profiles of home-dwelling older people: focus on sociodemographic and socioeconomic characteristics. AB - OBJECTIVES: This paper investigates risk profiles of frailty among older people, as these are essential for detecting those individuals at risk for adverse outcomes and to undertake specific preventive actions. Frailty is not only a physical problem, but also refers to emotional, social, and environmental hazards. METHODS: Using data generated from the Belgian Ageing Studies, a cross sectional study (n = 28,049), we tested a multivariate regression model that included sociodemographic and socioeconomic indicators as well as four dimensions of frailty, for men and women separately. RESULTS: The findings indicated that for both men and women, increased age, having no partner, having moved house in the previous 10 years, having a lower educational level and having a lower household income are risk characteristics for frailty. Moreover, when looking at the different frailty domains, different risk profiles arose, and gender-specific risk characteristics were detected. DISCUSSION: This paper elaborates on practical implications, and formulates a number of future research recommendations to tackle frailty in an aging society. The conclusion demonstrates the necessity for a thorough knowledge of risk profiles of frailty, as this will save both time and money and permit preventive actions to be more individually tailored. PMID- 27267784 TI - Goal saliency boosts infants' action prediction for human manual actions, but not for mechanical claws. AB - Previous research indicates that infants' prediction of the goals of observed actions is influenced by own experience with the type of agent performing the action (i.e., human hand vs. non-human agent) as well as by action-relevant features of goal objects (e.g., object size). The present study investigated the combined effects of these factors on 12-month-olds' action prediction. Infants' (N=49) goal-directed gaze shifts were recorded as they observed 14 trials in which either a human hand or a mechanical claw reached for a small goal area (low saliency goal) or a large goal area (high-saliency goal). Only infants who had observed the human hand reaching for a high-saliency goal fixated the goal object ahead of time, and they rapidly learned to predict the action goal across trials. By contrast, infants in all other conditions did not track the observed action in a predictive manner, and their gaze shifts to the action goal did not change systematically across trials. Thus, high-saliency goals seem to boost infants' predictive gaze shifts during the observation of human manual actions, but not of actions performed by a mechanical device. This supports the assumption that infants' action predictions are based on interactive effects of action-relevant object features (e.g., size) and own action experience. PMID- 27267786 TI - Effect of micronized fenofibrate on microvascular complications of type 2 diabetes: a systematic review. AB - OBJECTIVE: Micronized fenofibrate prevents the progression of microvascular complications in type 2 diabetes, but no systematic review has summarized these effects. Therefore, we performed a systematic review to investigate the effects of micronized fenofibrate on type 2 diabetes-related microvascular complications. RESEARCH DESIGN AND METHODS: The PubMed database was systematically searched for trials in English language published between January 1990 and November 2015 that examined the effects of fenofibrate on microvascular complications in patients with type 2 diabetes. RESULTS: Thirteen trials of the 290 clinical studies reviewed met the inclusion criteria. Fenofibrate significantly slowed the progression of early diabetic retinopathy by 30 to 40% within 4 to 5 years in patients with type 2 diabetes mellitus and pre-existing retinopathy at baseline. Fenofibrate also consistently reduced the progression of urinary albumin excretion in the trials studied. One large study demonstrated a significant effect (47% reduction) of the drug on diabetes-related minor amputations. CONCLUSIONS: The available evidence supports the adjunctive early use of fenofibrate in type 2 diabetes mellitus for the prevention of microvascular complications, particularly in individuals presenting with the first signs of the complication and during the initial stages of the disease. PMID- 27267785 TI - Efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet for the treatment of adults with opioid dependence: A randomized trial. AB - This prospective, randomized, active-controlled, non-inferiority study evaluated the efficacy and safety of a sublingual buprenorphine/naloxone rapidly dissolving tablet (Zubsolv(r); buprenorphine/naloxone rapidly dissolving tablet) versus generic buprenorphine for induction of opioid maintenance among dependent adults. The study, conducted at 13 sites from June 2013 to January 2014, included a 2-day blinded induction phase and a 27-day open-label stabilization/maintenance phase. During the blinded induction, patients received fixed doses of buprenorphine/naloxone rapidly dissolving tablets or generic buprenorphine. During open-label stabilization/early maintenance, all patients received buprenorphine/naloxone rapidly dissolving tablets. The primary efficacy assessment was treatment retention at day 3; buprenorphine/naloxone rapidly dissolving tablets were considered non-inferior to generic buprenorphine if the lower limit of the 95% confidence interval for the difference between the treatments was >=-10% in patients retained on day 3. Secondary assessments included opioid withdrawal symptoms and cravings as measured using the Clinical Opiate Withdrawal Scale, the Subjective Opiate Withdrawal Scale, and the opioid cravings visual analogue scale. Safety was also assessed. A total of 313 patients were randomly assigned to induction with generic buprenorphine or buprenorphine/naloxone rapidly dissolving tablets. The mean age was 38.4 years, and the mean duration of opioid dependence was 12.4 years. For the primary efficacy assessment, 235 of 256 patients (91.8%) were retained at day 3 and continued to the maintenance phase. The lower limit of the 95% confidence interval was -13.7; thus, buprenorphine/naloxone rapidly dissolving tablets did not demonstrate non-inferiority to generic buprenorphine, and significantly more patients who received induction with generic buprenorphine (122/128 [95.3%]) were retained at day 3 compared with those who received induction with buprenorphine/naloxone rapidly dissolving tablets (113/128 [88.3%]; 95% confidence interval: -13.7, -0.4; p = 0.040). The rates of clinical response, as measured by the Clinical Opiate Withdrawal Scale, the Subjective Opiate Withdrawal Scale, and the visual analogue scale, were comparable among patients regardless of the induction medication. Treatment with buprenorphine/naloxone rapidly dissolving tablets was generally safe and reduced the severity of withdrawal symptoms and cravings. PMID- 27267787 TI - Synthesis and Characterization of Water-Soluble Conjugated Oligoelectrolytes for Near-Infrared Fluorescence Biological Imaging. AB - Near-infrared (NIR) fluorophores attract increasing attention as a molecular marker (or probe) for in vivo and in vitro biological fluorescence imaging. Three types of new NIR fluorescent conjugated oligoelectrolytes (COEs: Q-FlTBTTFl, Q FlBBTFl, and Q-FlTBBTTFl) are synthesized with quaternized ammonium ionic groups in their side-chains for water solubility. The emission wavelength is modulated in the range 600-1300 nm, by adjusting the intramolecular charge transfer in the molecular backbone based on the electron-rich fluorene (and/or thiophene) and electron-deficient benzo[2,1,3]thiadiazole (or benzo[1,2-c:4,5 c']bis[1,2,5]thiadiazole) moieties. The COEs show a remarkably larger Stokes shift (147-276 nm) compared to commercial rhodamine and cyanine dyes in water, avoiding self-quenching and interference from the excitation backscattered light. The photoluminescence (PL) quantum efficiency is improved substantially by up to 27.8% in water by fabricating a vesicular complex, COE/v, with a block ionomer, poly[(ethylene oxide)-block-(sodium 2-acrylamido-2-methyl-1-propanesulfonate)]. In vitro cellular uptake images with the COEs are obtained with good biocompatibility by confocal single-photon and two-photon microscopy. The ex vivo and in vivo images of a mouse xenograft model treated with the Q-FlBBTFl/v exhibit a substantially stronger fluorescence signal at the tumor site than at the other organs, highlighting the potential of the COE/v as an NIR fluorescent imaging agent for the diagnosis of cancer. PMID- 27267789 TI - Novel heterozygous mutation in YAP1 in a family with isolated ocular colobomas. PMID- 27267790 TI - Atomic Scale Interface Manipulation, Structural Engineering, and Their Impact on Ultrathin Carbon Films in Controlling Wear, Friction, and Corrosion. AB - Reducing friction, wear, and corrosion of diverse materials/devices using <2 nm thick protective carbon films remains challenging, which limits the developments of many technologies, such as magnetic data storage systems. Here, we present a novel approach based on atomic scale interface manipulation to engineer and control the friction, wear, corrosion, and structural characteristics of 0.7-1.7 nm carbon-based films on CoCrPt:oxide-based magnetic media. We demonstrate that when an atomically thin (~0.5 nm) chromium nitride (CrNx) layer is sandwiched between the magnetic media and an ultrathin carbon overlayer (1.2 nm), it modifies the film-substrate interface, creates various types of interfacial bonding, increases the interfacial adhesion, and tunes the structure of carbon in terms of its sp(3) bonding. These contribute to its remarkable functional properties, such as stable and lowest coefficient of friction (~0.15-0.2), highest wear resistance and better corrosion resistance despite being only ~1.7 nm thick, surpassing those of ~2.7 nm thick current commercial carbon overcoat (COC) and other overcoats in this work. While this approach has direct implications for advancing current magnetic storage technology with its ultralow thickness, it can also be applied to advance the protective and barrier capabilities of other ultrathin materials for associated technologies. PMID- 27267788 TI - In Vitro Resistance Development to Nemonoxacin in Streptococcus pneumoniae: A Unique Profile for a Novel Nonfluorinated Quinolone. AB - Selection of resistant strains in Streptococcus pneumoniae was studied in vitro with nemonoxacin, a novel nonfluorinated quinolone (NFQ), in comparison with quinolone benchmarks, ciprofloxacin, garenoxacin, and gatifloxacin. In stepwise resistance selection studies, a 256-fold loss of potency was observed after three to four steps of exposure to ciprofloxacin or garenoxacin. In contrast, the loss of potency was limited to eightfold after three steps of exposure to nemonoxacin and repeated attempts to isolate highly resistant organisms after four steps of exposure yielded isolates that could not be subcultured in liquid medium. The quinolone resistance-determining regions of the target genes, parC, parE, gyrA, and gyrB, were analyzed through DNA sequencing. Known mutations, especially in the hotspots of parC and gyrA, were selected with exposure to garenoxacin, ciprofloxacin, and gatifloxacin. In contrast, mutations selected with nemonoxacin were limited to GyrA, GyrB, and ParE, sparing ParC, which is known as a key driver of resistance in clinical isolates of S. pneumoniae. This observation is consistent with previous data using other NFQs, which showed no loss of potency due to ParC mutations in clinical isolates. This apparently unique feature of nemonoxacin is potentially attributable to the structural uniqueness of the NFQs, distinguishing them from the fluoroquinolones that are commonly prescribed for infections by S. pneumoniae. PMID- 27267791 TI - Complexity and nonlinear biomarkers in emotional disorders: A meta-analytic study. AB - This meta-analysis aimed at gathering and summarising the findings on nonlinear biomarkers in the field of emotional disorders under the hypothesis that diseased systems show lowered complexity and hence less flexibility to adjust daily contexts. Scientific manuscripts from 1970 to 2014 were reviewed, 58 articles were analysed, and independent meta-analyses on anxiety disorders, bipolar disorders, and depressive disorders were conducted. Results revealed that anxious patients exhibited lower complexity than controls (p<0.05) despite panic patients showed more irregular respiratory activity. Inconclusive results were found for bipolar patients but pointed to higher randomness when suffering manic episodes. Finally, depressed patients showed a loss of complexity in the cardiac system and a loss of orderliness (despite a higher complexity) in brain and stress-related hormonal systems. As a conclusion, our findings highlight that either a loss of complexity or a loss of ordered complexity characterise the physiological systems of patients with emotional disorders. Several considerations for complexity, its related measurements, and suggestions for further research are discussed. PMID- 27267793 TI - Soft Liner/Clip Attachment for Bar-Retained Implant Overdentures: A Technical Note. PMID- 27267792 TI - Food, nutrients and nutraceuticals affecting the course of inflammatory bowel disease. AB - Inflammatory bowel diseases (ulcerative colitis; Crohn's disease) are debilitating relapsing inflammatory disorders affecting the gastrointestinal tract, with deleterious effect on quality of life, and increasing incidence and prevalence. Mucosal inflammation, due to altered microbiota, increased intestinal permeability and immune system dysfunction underlies the symptoms and may be caused in susceptible individuals by different factors (or a combination of them), including dietary habits and components. In this review we describe the influence of the Western diet, obesity, and different nutraceuticals/functional foods (bioactive peptides, phytochemicals, omega 3-polyunsaturated fatty acids, vitamin D, probiotics and prebiotics) on the course of IBD, and provide some hints that could be useful for nutritional guidance. Hopefully, research will soon offer enough reliable data to slow down the spread of the disease and to make diet a cornerstone in IBD therapy. PMID- 27267794 TI - Effects of different surface modification and contents on municipal solid waste incineration fly ash/epoxy composites. AB - Incineration fly ash, a waste from municipal solid waste incineration plant can be used to replace conventional filler as reinforcing filler to enhance the mechanical strength of a composite. Surface modification was performed on the incineration fly ash before mixing into the soft polymer matrix so as to improve interfacial bond of the filler and epoxy resin. In this study, detailed characterisation of mechanical, morphological and leaching behaviours of municipal solid waste incineration (MSWI) fly ash infused composite has been carried out. Flexural and tensile test was conducted to determine the effect on mechanical properties of the composite by varying the concentration of incineration fly ash filler added into polymer matrix and surface modification of incineration fly ash filler using silane coupling agent and colloidal mesoporous silica (CMS). The results indicated that composite infused with incineration fly ash filler surface treated with CMS shown improvement on the tensile and flexural strengths. In addition, SEM images showed that surface modification of incineration fly ash with colloidal mesoporous silica enhanced the interfacial bonding with polymer resin which explained the improvement of mechanical strength. Leaching test showed result of toxic metals such as Pb, Zn, Fe, Cu, Cr, Cd and Rb immobilised in the polymer matrix of the composite. Hence, the use of MSWI fly ash as reinforcing filler in the composite appears green and sustainable because this approach is a promising opportunity to substitute valuable raw material with MSWI fly ash. PMID- 27267796 TI - The era of phased introduction of new implants. PMID- 27267795 TI - Surrogate markers of long-term outcome in primary total hip arthroplasty: A systematic review. AB - OBJECTIVES: High failure rates of metal-on-metal hip arthroplasty implants have highlighted the need for more careful introduction and monitoring of new implants and for the evaluation of the safety of medical devices. The National Joint Registry and other regulatory services are unable to detect failing implants at an early enough stage. We aimed to identify validated surrogate markers of long term outcome in patients undergoing primary total hip arthroplasty (THA). METHODS: We conducted a systematic review of studies evaluating surrogate markers for predicting long-term outcome in primary THA. Long-term outcome was defined as revision rate of an implant at ten years according to National Institute of Health and Care Excellence guidelines. We conducted a search of Medline and Embase (OVID) databases. Separate search strategies were devised for the Cochrane database and Google Scholar. Each search was performed to include articles from the date of their inception to June 8, 2015. RESULTS: Our search strategy identified 1082 studies of which 115 studies were included for full article review. Following review, 17 articles were found that investigated surrogate markers of long-term outcome. These included one systematic review, one randomised control trial (RCT), one case control study and 13 case series. Validated surrogate markers included Radiostereometric Analysis (RSA) and Einzel Bild-Rontgen-Analyse (EBRA), each measuring implant migration and wear. We identified five RSA studies (one systematic review and four case series) and four EBRA studies (one RCT and three case series). Patient Reported Outcome Measures (PROMs) at six months have been investigated but have not been validated against long-term outcomes. CONCLUSIONS: This systematic review identified two validated surrogate markers of long-term primary THA outcome: RSA and EBRA, each measuring implant migration and wear. We recommend the consideration of RSA in the pre market testing of new implants. EBRA can be used to investigate acetabular wear but not femoral migration. Further studies are needed to validate the use of PROMs for post-market surveillance.Cite this article: T. T. Malak, J. A. J. Broomfield, A. J. R. Palmer, S. Hopewell, A. Carr, C. Brown, D. Prieto-Alhambra, S. Glyn-Jones. Surrogate markers of long-term outcome in primary total hip arthroplasty: A systematic review. Bone Joint Res 2016;5:206-214. DOI: 10.1302/2046-3758.56.2000568. PMID- 27267797 TI - Presenting risk information in sexual and reproductive health care. AB - OBJECTIVES: Presenting risk information to patients is an important part of clinical encounters. Good risk communication improves patient satisfaction with their care and the decisions they make. In sexual and reproductive healthcare (SRH), women frequently need to make decisions based on their perceived risk. Risk perception can be altered by how actual risk is presented to patients. METHODS: Databases were searched using MeSH terms combined with a keyword search for articles relevant to SRH; the search was limited to English language. RESULTS: Personalised risk communication where a risk score is provided, increases knowledge and slightly increases uptake of screening tests. Decision aids improve a patient's knowledge of the options, create realistic expectations of their benefits and harms, reduce difficulty with decision-making, and increase participation in the process. The most effective way to present risks uses a range of structured, tailored presentation styles; interactive formats are best. Framing the information improves patient understanding. Most people understand natural frequencies or event rates better than probability formats with varying denominators. Expressing changes in risk as an absolute risk reduction or relative risk reduction with baseline risk formats improves understanding. Descriptive terms such as 'low risk' or 'high risk' should be quantified as a frequency rather than a percentage. Using a consistent denominator to portray risk is recommended. Using the 'number needed to treat' and visual aids puts benefits or risks into perspective. The duration of risk should be presented. CONCLUSION: Presenting risk information to patients can be optimised using a number of strategies. PMID- 27267798 TI - On being an expert witness in sexual and reproductive health. AB - A new generation of expert witnesses in sexual and reproductive health is needed, including those in nursing as well as medical roles. Being an expert witness is a significant commitment alongside clinical work. Nevertheless, the work is stimulating and rewarding. Training is essential before starting medicolegal work. In particular expert witnesses need to be able to apply appropriate legal tests to the evidence, to deal with the range of expert opinion on a matter, and explain clearly what constitutes an appropriate standard of care for a clinician in their discipline and specialty. Expert witnesses must be aware of pitfalls such as being sued for substandard work and being reported to their professional regulator for straying outside their area of expertise. Expert witnesses must be truly independent and ideally their reports should be the same whoever they receive their instructions from. In addition to report writing, expert witnesses are required to comment on court documents, participate in conferences with a barrister and hold formal discussions with an opposing expert witness. Expert witnesses need to be administratively efficient and responsive. Although appearance in court is not that common, this is an essential part of the role. Apart from litigation in the civil courts, other types of case may present themselves including patent cases, work in the Court of Protection and health professionals' Fitness to Practise hearings. PMID- 27267799 TI - Zika virus misinformation on the internet. PMID- 27267800 TI - Combining the High Tech with the Soft Touch: Population Health Management Using eHealth and Peer Support. PMID- 27267801 TI - Extended Aromatic and Heteroaromatic Ring Systems in the Chalcone-Flavanone Molecular Switch Scaffold. AB - Previous work on the o-hydroxychalcone/flavanone molecular switching scaffold showed that simple substitutions alter the pH range in which rapid interconversion occurs. Herein, more impactful structural modifications were performed via alteration of the characteristic phenyl rings to alternative aromatic systems. It was determined that the scaffold was still viable after these changes and that the range of accessible midpoint pH values was markedly increased. To further explore the switch's scope, scaffolds able to have multiple switching events were also investigated. PMID- 27267802 TI - Probiotic Lactobacillus gasseri SBT2055 improves glucose tolerance and reduces body weight gain in rats by stimulating energy expenditure. AB - Probiotic Lactobacillus gasseri SBT2055 (LG2055) reduces postprandial TAG absorption and exerts anti-obesity effects in rats and humans; however, the underlying mechanisms are not fully understood. In the present study, we addressed the mechanistic insights of the anti-obesity activity of LG2055 by feeding Sprague-Dawley rats diets containing skimmed milk fermented or not by LG2055 for 4 weeks and by analysing energy expenditure, glucose tolerance, the levels of SCFA in the caecum and serum inflammatory markers. Rats fed the LG2055 containing diet demonstrated significantly higher carbohydrate oxidation in the dark cycle (active phase for rats) compared with the control group, which resulted in a significant increase in energy expenditure. LG2055 significantly reduced cumulative blood glucose levels (AUC) compared with the control diet after 3 weeks and increased the molar ratio of butyrate:total SCFA in the caecum after 4 weeks. Furthermore, the LG2055-supplemented diet significantly reduced the levels of serum amyloid P component - an indicator of the inflammatory process. In conclusion, our results demonstrate that, in addition to the inhibition of dietary TAG absorption reported previously, the intake of probiotic LG2055 enhanced energy expenditure via carbohydrate oxidation, improved glucose tolerance and attenuated inflammation, suggesting multiple additive and/or synergistic actions underlying the anti-obesity effects exerted by LG2055. PMID- 27267803 TI - Prediction of Excited-State Energies and Singlet-Triplet Gaps of Charge-Transfer States Using a Restricted Open-Shell Kohn-Sham Approach. AB - Organic molecules with charge-transfer (CT) excited states are widely used in industry and are especially attractive as candidates for fabrication of energy efficient OLEDs, as they can harvest energy from nonradiative triplets by means of thermally activated delayed fluorescence (TADF). It is therefore useful to have computational protocols for accurate estimation of their electronic spectra in order to screen candidate molecules for OLED applications. However, it is difficult to predict the photophysical properties of TADF molecules with LR TDDFT, as semilocal LR-TDDFT is incapable of accurately modeling CT states. Herein, we study absorption energies, emission energies, zero-zero transition energies, and singlet-triplet gaps of TADF molecules using a restricted open shell Kohn-Sham (ROKS) approach instead and discover that ROKS calculations with semilocal hybrid functionals are in good agreement with experiments-unlike TDDFT, which significantly underestimates energy gaps. We also propose a cheap computational protocol for studying excited states with large CT character that is found to give good agreement with experimental results without having to perform any excited-state geometry optimizations. PMID- 27267804 TI - WISP1 is a novel adipokine linked to metabolic parameters in gestational diabetes mellitus. AB - OBJECTIVE: To investigate Wnt1-inducible signaling pathway protein-1 (WISP1) levels and their correlation with metabolic parameters in pregnant women with gestational diabetes mellitus (GDM) and non-GDM healthy pregnant women. MATERIALS AND METHODS: In this prospective cross-sectional study, the study group was composed of 62 women with GDM and 73 healthy pregnant women matched for age, body mass index (BMI) and gestational age. Blood samples were collected at 25-29th gestational week. Serum WISP1, betatrophin, glucose, fasting insulin, glycosylated hemoglobin A1c, total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, C reactive protein, alanine aminotransferase and creatinine levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) values was calculated. The level of significance was accepted as p < 0.05. RESULTS: Circulating WISP1 in the GDM group was significantly higher than the control group (p <0.001). Further, WISP1 was positively correlated with BMI, HOMA-IR values and fasting glucose, fasting insulin, triglyceride, betatrophin levels. BMI, HOMA-IR and betatrophin independently and positively predicted WISP1 levels. CONCLUSION: These results demonstrate a relationship between WISP1 and the metabolic parameters of GDM. And, WISP1 might be involved in the pathophysiology of GDM. As a part of this pathophysiological mechanism, the activation of WISP1 and betatrophin might take place through several ways; WISP1 and betatrophin might either use same signaling pathways and potentiate each other or they might also constitute the sequential steps of a common pathway. PMID- 27267805 TI - Polycyclic Aromatic Hydrocarbon Affects Acetic Acid Production during Anaerobic Fermentation of Waste Activated Sludge by Altering Activity and Viability of Acetogen. AB - Till now, almost all the studies on anaerobic fermentation of waste activated sludge (WAS) for bioproducts generation focused on the influences of operating conditions, pretreatment methods and sludge characteristics, and few considered those of widespread persistent organic pollutants (POPs) in sludge, for example, polycyclic aromatic hydrocarbons (PAHs). Herein, phenanthrene, which was a typical PAH and widespread in WAS, was selected as a model compound to investigate its effect on WAS anaerobic fermentation for short-chain fatty acids (SCFAs) accumulation. Experimental results showed that the concentration of SCFAs derived from WAS was increased in the presence of phenanthrene during anaerobic fermentation. The yield of acetic acid which was the predominant SCFA in the fermentation reactor with the concentration of 100 mg/kg dry sludge was 1.8 fold of that in the control. Mechanism exploration revealed that the present phenanthrene mainly affected the acidification process of anaerobic fermentation and caused the shift of the microbial community to benefit the accumulation of acetic acid. Further investigation showed that both the activities of key enzymes (phosphotransacetylase and acetate kinase) involved in acetic acid production and the quantities of their corresponding encoding genes were enhanced in the presence of phenanthrene. Viability tests by determining the adenosine 5' triphosphate content and membrane potential confirmed that the acetogens were more viable in anaerobic fermentation systems with phenanthrene, which resulted in the increased production of acetic acid. PMID- 27267806 TI - HDAC6 promotes cell proliferation and confers resistance to temozolomide in glioblastoma. AB - Histone deacetylases are considered to be among the most promising targets in drug development for cancer therapy. Histone deacetylase 6 (HDAC6) is a unique cytoplasmic enzyme that regulates many biological processes involved in tumorigenesis through its deacetylase and ubiquitin-binding activities. Here, we report that HDAC6 is overexpressed in glioblastoma tissues and cell lines. Overexpression of HDAC6 promotes the proliferation and spheroid formation of glioblastoma cells. HDAC6 overexpression confers resistance to temozolomide (TMZ) mediated cell proliferation inhibition and apoptosis induction. Conversely, knockdown of HDAC6 inhibits cell proliferation, impairs spheroid formation and sensitizes glioblastoma cells to TMZ. The inhibition of HDAC6 deacetylase activity by selective inhibitors inhibits the proliferation of glioblastoma cells and induces apoptosis. HDAC6 selective inhibitors can sensitize glioblastoma cells to TMZ. Moreover, we showed that HDAC6 mediated EGFR stabilization might partly account for its oncogenic role in glioblastoma. TMZ resistant glioblastoma cells showed higher expression of HDAC6 and more activation of EGFR. HDAC6 inhibitors decrease EGFR protein levels and impair the activation of the EGFR pathway. Taken together, our results suggest that the inhibition of HDAC6 may be a promising strategy for the treatment of glioblastoma. PMID- 27267808 TI - Developing oxygen-enhanced magnetic resonance imaging as a prognostic biomarker of radiation response. AB - Oxygen-Enhanced Magnetic Resonance Imaging (OE-MRI) techniques were evaluated as potential non-invasive predictive biomarkers of radiation response. Semi quantitative blood-oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) contrast, and quantitative responses of relaxation rates (DeltaR1 and DeltaR2*) to an oxygen breathing challenge during hypofractionated radiotherapy were applied. OE-MRI was performed on subcutaneous Dunning R3327-AT1 rat prostate tumors (n=25) at 4.7 T prior to each irradiation (2F * 15 Gy) to the gross tumor volume. Response to radiation, while inhaling air or oxygen, was assessed by tumor growth delay measured up to four times the initial irradiated tumor volume (VQT). Radiation-induced hypoxia changes were confirmed using a double hypoxia marker assay. Inhaling oxygen during hypofractionated radiotherapy significantly improved radiation response. A correlation was observed between the difference in the 2nd and 1st DeltaR1 (DeltaDeltaR1) and VQT for air breathing rats. The TOLD response before the 2nd fraction showed a moderate correlation with VQT for oxygen breathing rats. The correlations indicate useful prognostic factors to predict tumor response to hypofractionation and could readily be applied for patient stratification and personalized radiotherapy treatment planning. PMID- 27267809 TI - Smac mimetic triggers necroptosis in pancreatic carcinoma cells when caspase activation is blocked. AB - Evasion of apoptosis represents a key mechanism of treatment resistance of pancreatic cancer (PC) and contributes to the poor prognosis of this cancer type. Here, we report that induction of necroptosis is an alternative strategy to trigger programmed cell death in apoptosis-resistant PC cells. We show that the second mitochondrial activator of caspases (Smac) mimetic BV6 that antagonizes inhibitor of apoptosis (IAP) proteins induces necroptosis in PC cells in which apoptosis is blocked by the caspase inhibitor zVAD.fmk. Intriguingly, BV6 switches autocrine/paracrine production of tumor necrosis factor (TNF)alpha by PC cells into a death signal and also acts in concert with exogenously supplied TNFalpha to trigger necroptosis, when caspase activation is simultaneously blocked. BV6 stimulates TNFalpha production and formation of the receptor interacting protein (RIP)1/RIP3-containing necrosome complex in PC cells. Knockdown of TNF receptor 1 (TNFR1) protects PC cells from BV6- or BV6/TNFalpha mediated cell death, demonstrating that TNFalpha autocrine/paracrine signaling by PC cells contributes to BV6-induced necroptosis. Importantly, genetic silencing of receptor interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain like protein (MLKL) significantly rescues PC cells from BV6- or BV6/TNFalpha induced cell death. Similarly, pharmacological inhibition of RIP1, RIP3 or MLKL significantly reduces BV6- or BV6/TNFalpha-stimulated cell death. By demonstrating that Smac mimetics can bypass resistance to apoptosis by triggering necroptosis as an alternative form of programmed cell death, our findings have important implications for the design of new treatment concepts for PC. PMID- 27267807 TI - Combined targeting of TGF-beta, EGFR and HER2 suppresses lymphangiogenesis and metastasis in a pancreatic cancer model. AB - Pancreatic ductal adenocarcinomas (PDACs) are aggressive with frequent lymphatic spread. By analysis of data from The Cancer Genome Atlas, we determined that ~35% of PDACs have a pro-angiogenic gene signature. We now show that the same PDACs exhibit increased expression of lymphangiogenic genes and lymphatic endothelial cell (LEC) markers, and that LEC abundance in human PDACs correlates with endothelial cell microvessel density. Lymphangiogenic genes and LECs are also elevated in murine PDACs arising in the KRC (mutated Kras; deleted RB) and KIC (mutated Kras; deleted INK4a) genetic models. Moreover, pancreatic cancer cells (PCCs) derived from KRC tumors express and secrete high levels of lymphangiogenic factors, including the EGF receptor ligand, amphiregulin. Importantly, TGF-beta1 increases lymphangiogenic genes and amphiregulin expression in KRC PCCs but not in murine PCCs that lack SMAD4, and combinatorial targeting of the TGF-beta type I receptor (TbetaRI) with LY2157299 and EGFR/HER2 with lapatinib suppresses tumor growth and metastasis in a syngeneic orthotopic model, and attenuates tumor lymphangiogenesis and angiogenesis while reducing lymphangiogenic genes and amphiregulin and enhancing apoptosis. Therefore, this combination could be beneficial in PDACs with lymphangiogenic or angiogenic gene signatures. PMID- 27267811 TI - Bedtime Stories that Work: The Effect of Protagonist Liking on Narrative Persuasion. AB - The experiment described in this article draws on affective disposition theory to clarify how protagonist likeability influences participants' sleep hygiene related self-efficacy and outcome expectations immediately after media exposure and 3 days later. Results indicate that protagonist likeability is an important factor in narrative persuasion. Protagonist likeability did not directly affect participants' sleep hygiene-related self-efficacy immediately postexposure, but it did influence self-efficacy 3 days later. The dislikeable protagonist influenced self-efficacy more than the likeable protagonist. Further, protagonist likeability did not directly affect outcome expectations either immediately postexposure or 3 days later. However, mediation analyses demonstrated that protagonist likeability indirectly influenced both self-efficacy and outcome expectations via perceived liking of the protagonist immediately after exposure and 3 days later. Implications of these findings are further discussed. PMID- 27267810 TI - Harnessing Fluorine-Sulfur Contacts and Multipolar Interactions for the Design of p53 Mutant Y220C Rescue Drugs. AB - Many oncogenic mutants of the tumor suppressor p53 are conformationally unstable, including the frequently occurring Y220C mutant. We have previously developed several small-molecule stabilizers of this mutant. One of these molecules, PhiKan083, 1-(9-ethyl-9H-carbazole-3-yl)-N-methylmethanamine, binds to a mutation induced surface crevice with a KD = 150 MUM, thereby increasing the melting temperature of the protein and slowing its rate of aggregation. Incorporation of fluorine atoms into small molecule ligands can substantially improve binding affinity to their protein targets. We have, therefore, harnessed fluorine-protein interactions to improve the affinity of this ligand. Step-wise introduction of fluorines at the carbazole ethyl anchor, which is deeply buried within the binding site in the Y220C-PhiKan083 complex, led to a 5-fold increase in affinity for a 2,2,2-trifluoroethyl anchor (ligand efficiency of 0.3 kcal mol(-1) atom( 1)). High-resolution crystal structures of the Y220C-ligand complexes combined with quantum chemical calculations revealed favorable interactions of the fluorines with protein backbone carbonyl groups (Leu145 and Trp146) and the sulfur of Cys220 at the mutation site. Affinity gains were, however, only achieved upon trifluorination, despite favorable interactions of the mono- and difluorinated anchors with the binding pocket, indicating a trade-off between energetically favorable protein-fluorine interactions and increased desolvation penalties. Taken together, the optimized carbazole scaffold provides a promising starting point for the development of high-affinity ligands to reactivate the tumor suppressor function of the p53 mutant Y220C in cancer cells. PMID- 27267812 TI - Two new phenolic compounds from the seeds of Machilus yunnanensis. AB - Chemical constituents investigation on the seeds of Machilus yunnanensis led to two new phenolic compounds 8-O-acetyl-phenylethanoid-4-O-beta-D-glucopyranoside (1) and (E)-2,3-bis(4-hydroxyphenyl)acrylaldehyde (2), together with 16 known compounds. Their structures were elucidated on the basis of spectroscopic data analysis (IR, MS, 1D, and 2D NMR). Meanwhile, compounds 1-3, 6-13, 17, and 18 were evaluated for vasorelaxant effects on the rat endothelium-intact thoracic aorta rings precontracted with phenylephrine (PE) or KCl. The bioassay results showed that compound 17 had significant vasorelaxant effect on the endothelium intact thoracic aorta rings precontracted with KCl. PMID- 27267813 TI - Effects of thalamic deep brain stimulation on spontaneous language production. AB - The thalamus is thought to contribute to language-related processing, but specifications of this notion remain vague. An assessment of potential effects of thalamic deep brain stimulation (DBS) on spontaneous language may help to delineate respective functions. For this purpose, we analyzed spontaneous language samples from thirteen (six female / seven male) patients with essential tremor treated with DBS of the thalamic ventral intermediate nucleus (VIM) in their respective ON vs. OFF conditions. Samples were obtained from semi structured interviews and examined on multidimensional linguistic levels. In the VIM-DBS ON condition, participants used a significantly higher proportion of paratactic as opposed to hypotactic sentence structures. This increase correlated negatively with the change in the more global cognitive score, which in itself did not change significantly. In conclusion, VIM-DBS appears to induce the use of a simplified syntactic structure. The findings are discussed in relation to concepts of thalamic roles in language-related cognitive behavior. PMID- 27267814 TI - Lipid-based dispersions of exemestane for improved dissolution rate and intestinal permeability: in vitro and ex vivo characterization. AB - Current study aimed to develop lipid dispersions of poorly water soluble exemestane by employing lipid carriers such as Gelucire 44/14 and TPGS with porous calcium silicate (PCS) as an adsorbent carrier and formulate into a solid dosage form. The lipid dispersions at 1:5 ratio showed the highest solubility and dissolution compared to pure exemestane. Further, the ex vivo intestinal permeation studies showed improved apparent permeability (Papp, cm/s) of exemestane from the lipid dispersions (GLD1:5 1.3 * 10-2 cm/s; TLD1:5 1.8 * 10-2 cm/s) compared to pure exemestane (0.7 * 10-2 cm/s). The optimized lipid dispersions (GLD1:5 and TLD1:5) were evaluated for scalability to develop into capsules. PMID- 27267815 TI - Preparation time influences ankle and knee joint control during dynamic change of direction movements. AB - The influence of preparation time on ankle joint biomechanics during highly dynamic movements is largely unknown. The aim of this study was to evaluate the impact of limited preparation time on ankle joint loading during highly dynamic run-and-cut movements. Thirteen male basketball players performed 45 degrees sidestep-cutting and 180 degrees -turning manoeuvres in reaction to light signals which appeared during the approach run. Both movements were executed under (1) an easy condition, in which the light signal appeared very early, (2) a medium condition and (3) a hard condition with very little time to prepare the movements. Maximum ankle inversion angles, moments and velocities during ground contact, as well as EMG signals of three lower extremity muscles, were analysed. In 180 degrees -turning movements, reduced preparation time led to significantly increased maximum ankle inversion velocities. Muscular activation levels, however, did not change. Increased inversion velocities, without accompanying changes in muscular activation, may have the potential to destabilise the ankle joint when less preparation time is available. This may result in a higher injury risk during turning movements and should therefore be considered in ankle injury research and the aetiology of ankle sprains. PMID- 27267816 TI - Complete remission of disseminated granulomatous dermatitis related to chronic eosinophilic leukemia following allogeneic stem cell transplantation. PMID- 27267818 TI - Prostatectomy vs radiation therapy for prostate cancer: The (still) unsolved dilemma. PMID- 27267817 TI - AISF position paper on liver transplantation and pregnancy: Women in Hepatology Group, Italian Association for the Study of the Liver (AISF). AB - After the first successful pregnancy in a liver transplant recipient in 1978, much evidence has accumulated on the course, outcomes and management strategies of pregnancy following liver transplantation. Generally, liver transplantation restores sexual function and fertility as early as a few months after transplant. Considering that one third of all liver transplant recipients are women, that approximately one-third of them are of reproductive age (18-49 years), and that 15% of female liver transplant recipients are paediatric patients who have a >70% probability of reaching reproductive age, the issue of pregnancy after liver transplantation is rather relevant, and obstetricians, paediatricians, and transplant hepatologists ever more frequently encounter such patients. Pregnancy outcomes for both the mother and infant in liver transplant recipients are generally good, but there is an increased incidence of preterm delivery, hypertension/preeclampsia, foetal growth restriction, and gestational diabetes, which, by definition, render pregnancy in liver transplant recipients a high-risk one. In contrast, the risk of congenital anomalies and the live birth rate are comparable to those of the general population. Currently there are still no robust guidelines on the management of pregnancies after liver transplantation. The aim of this position paper is to review the available evidence on pregnancy in liver transplant recipients and to provide national Italian recommendations for clinicians caring for these patients. PMID- 27267819 TI - Performance of recidivism risk assessment instruments in U.S. correctional settings. AB - With the population of adults under correctional supervision in the United States at an all-time high, psychologists and other professionals working in U.S. correctional agencies face mounting pressures to identify offenders at greater risk of recidivism and to guide treatment and supervision recommendations. Risk assessment instruments are increasingly being used to assist with these tasks; however, relatively little is known regarding the performance of these tools in U.S. correctional settings. In this review, we synthesize the findings of studies examining the predictive validity of assessments completed using instruments designed to predict general recidivism risk, including committing a new crime and violating conditions of probation or parole, among adult offenders in the United States. We searched for studies conducted in the United States and published between January 1970 and December 2012 in peer-reviewed journals, government reports, master's theses, and doctoral dissertations using PsycINFO, the U.S. National Criminal Justice Reference Service Abstracts, and Google. We identified 53 studies (72 samples) conducted in U.S. correctional settings examining the predictive validity of 19 risk assessment instruments. The instruments varied widely in the number, type, and content of their items. For most instruments, predictive validity had been examined in 1 or 2 studies conducted in the United States that were published during the reference period. Only 2 studies reported on interrater reliability. No instrument emerged as producing the "most" reliable and valid risk assessments. Findings suggest the need for continued evaluation of the performance of instruments used to predict recidivism risk in U.S. correctional agencies. (PsycINFO Database Record PMID- 27267820 TI - Ultrafast Band Structure Control of a Two-Dimensional Heterostructure. AB - The electronic structure of two-dimensional (2D) semiconductors can be significantly altered by screening effects, either from free charge carriers in the material or by environmental screening from the surrounding medium. The physical properties of 2D semiconductors placed in a heterostructure with other 2D materials are therefore governed by a complex interplay of both intra- and interlayer interactions. Here, using time- and angle-resolved photoemission, we are able to isolate both the layer-resolved band structure and, more importantly, the transient band structure evolution of a model 2D heterostructure formed of a single layer of MoS2 on graphene. Our results reveal a pronounced renormalization of the quasiparticle gap of the MoS2 layer. Following optical excitation, the band gap is reduced by up to ~400 meV on femtosecond time scales due to a persistence of strong electronic interactions despite the environmental screening by the n-doped graphene. This points to a large degree of tunability of both the electronic structure and the electron dynamics for 2D semiconductors embedded in a van der Waals-bonded heterostructure. PMID- 27267821 TI - Role of astrocyte activation in fine particulate matter-enhancement of existing ischemic stroke in Sprague-Dawley male rats. AB - Exposure to particulate matter (PM) with an aerodynamic diameter of less than 2.5 MUm (PM2.5) is associated with increased risk of ischemic stroke, but potential neurotoxic mechanisms remain to be determined. In this study, adult male Sprague- Dawley (SD) rats were divided into four groups as follows: control (CON), PM2.5 exposure (PM alone), ischemic stroke (IS), and ischemic stroke and PM2.5 (IS-PM). Ischemic stroke groups were prepared by middle cerebral artery occlusion (MCAO), and neurobehavior was assessed daily for 7 consecutive days. The control group was administered intranasally 20 MUl PBS, while PM2.5 alone was given as 20 MUl of PM2.5 (10 mg/ml) intranasal daily for 7 consecutive days. The spontaneous locomotion and exploratory behavior of rats were assessed by the open field test. Cells positive for glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) were determined for astrocyte activation and inflammatory reactions. Neuronal edema and pyknosis in the cerebral cortex, hippocampus, and midbrain were observed in IS groups with or without PM2.5 treatment. Astrocyte activity was enhanced, whereas spontaneous locomotion and exploratory movements decreased in the IS-PM group. Data demonstrated that astrocytes activation and inflammatory reactions may play a role in IS and that exposure to PM2.5 may aggravate the neurobehavioral alterations observed in rats suffering from IS. PMID- 27267822 TI - Involvement of hypoxia-inducible factor-1 alpha (HIF-1alpha) in inhibition of benzene on mouse hematopoietic system. AB - Benzene is an occupational and environmental pollutant that damages the hematopoietic system through oxidant mechanisms. The aims of this study were to assess the role of oxidation in benzene-mediated damage by determination of the levels of reactive oxygen species (ROS) and to evaluate the role of hypoxia inducible factor-1alpha (HIF-1alpha) in this process. C57BL/6 mice were exposed to benzene at varying concentrations of 60, 150, or 300 mg/kg/d for 15 d. Mice in the benzene groups displayed weight loss, and hematologic consequences including decreased red and white blood cell counts, reduced platelet count, diminished hemoglobin content, and lower number of hematopoietic stem cells in bone marrow (BM). There was an elevated proportional neutrophil count and decrease in relative thymus weight. In BM there was a significant increase in ROS levels at 150 mg/kg benzene. However, as a result of diminished cellular viability, ROS levels were not markedly different between the 300-mg/kg benzene dose and the control, as the number of hematopoietic stem cells was reduced. HIF-1alpha expression and protein levels were decreased in BM cells at all doses of benzene. In conclusion, data indicated that HIF-1alpha may be involved in benzene-induced inhibition of mouse hematopoiesis and that oxidative stress may play a role in the observed toxicity. PMID- 27267823 TI - lncRNA UCA1 inhibits esophageal squamous-cell carcinoma growth by regulating the Wnt signaling pathway. AB - Esophageal squamous-cell carcinoma (ESCC) is one of the most common tumors worldwide. Recent studies suggested that long noncoding RNAs (lncRNAs) might play a key role in regulating cellular processes and cancer progression. One of the lncRNAs, urothelial carcinoma associated 1 (UCA1), is known to be dysregulated in several cancers, including bladder carcinoma, colorectal, melanoma, breast, gastric, and ESCC. However, contributions of UCA1 to ESCC remain largely undiscovered. In order to understand the role and mechanisms underlying UCA1 in ESCC, the association of UCA1 expression with risk of esophageal cancer development was determined in 106 esophageal cancer tissues of ESCC patients and adjacent normal tissues using real-time reverse-transcription polymerase chain reaction (PCR). The relative expression of UCA1 was significantly reduced in cancer versus adjacent normal tissues suggesting an enhanced risk of esophageal cancer. To investigate the biological functions of UCA1 in ESCC, it was of interest to examine whether overexpression of UCA1 might influence cell proliferation, apoptosis, cell cycle distribution, migration, and invasion in vitro using EC109 cells. Our results demonstrated that UCA1 decreased cell proliferation, migration, invasion, and cell cycle progression of EC109 cells. Further, mRNA microarray analysis of overexpressed UCA1 in EC109 cells revealed that abnormal expression of UCA1 also inhibited the Wnt signaling pathway. Gene levels of DKK1 were elevated while C-myc fell significantly in overexpressed UCA1 EC109 cells. Interestingly, Western blot demonstrated no significant differences in relative expression of CTNNB1 (beta-catenin) but marked reduction in beta catenin (active form) levels in both total and nuclear proteins. These results suggest that UCA1 may inhibit ESCC growth by regulating the Wnt signaling pathway. In conclusion, UCA1 may be a novel biomarker involved in ESCC development that may provide a potential therapeutic target for ESCC. PMID- 27267824 TI - Adaptive response in mouse bone-marrow stromal cells exposed to 900-MHz radiofrequency fields: Gamma-radiation-induced DNA strand breaks and repair. AB - The aim of this study was to examine whether radiofrequency field (RF) preexposure induced adaptive responses (AR) in mouse bone-marrow stromal cells (BMSC) and the mechanisms underlying the observed findings. Cells were preexposed to 900-MHz radiofrequency fields (RF) at 120 MUW/cm(2) power intensity for 4 h/d for 5 d. Some cells were subjected to 1.5 Gy gamma-radiation (GR) 4 h following the last RF exposure. The intensity of strand breaks in the DNA was assessed immediately at 4 h. Subsequently, some BMSC were examined at 30, 60, 90, or 120 min utilizing the alkaline comet assay and gamma-H2AX foci technique. Data showed no significant differences in number and intensity of strand breaks in DNA between RF-exposed and control cells. A significant increase in number and intensity of DNA strand breaks was noted in cells exposed to GR exposure alone. RF followed by GR exposure significantly decreased number of strand breaks and resulted in faster kinetics of repair of DNA strand breaks compared to GR alone. Thus, data suggest that RF preexposure protected cells from damage induced by GR. Evidence indicates that in RF-mediated AR more rapid repair kinetics occurs under conditions of GR-induced damage, which may be attributed to diminished DNA strand breakage. PMID- 27267825 TI - Analysis of the miRNA-mRNA networks in malignant transformation BEAS-2B cells induced by alpha-particles. AB - The aim of this study was to determine the toxicity induced by irradiation with alpha-particles on malignant transformation of immortalized human bronchial epithelial cells (BEAS-2B) using miRNA-mRNA networks. The expression of BEAS-2B cells was determined by measuring colony formation, mtDNA, mitochondrial membrane potential (MMP), and ROS levels. Changes in BEAS-2B cell gene expression were observed and quantified using microarrays that included an increase in 157 mRNA and 20 miRNA expression and a decrease in 77 mRNA and 48 miRNA. Bioinformatic software was used to analyze these different mRNA and miRNA, which indicated that miR-107 and miR-494 play an important role in alpha-particles-mediated cellular malignant transformation processes. The pathways related to systemic lupus erythematosus, cytokine-cytokine receptor interaction, MAPK signaling pathway, regulation of actin cytoskeleton, and cell adhesion molecules (CAMs) were stimulated, while those of ribosome, transforming growth factor (TGF)-beta signaling pathway, and metabolic pathways were inhibited. Data suggest that miRNA and mRNA play a crucial role in alpha-particles-mediated malignant transformation processes. It is worth noting that three target genes associated with lung cancer were identified and upregulated PEG 10 (paternally expressed gene 10), ARHGAP26, and IRS1. PMID- 27267826 TI - Radon-induced alterations in p53-mediated energy metabolism of malignantly transformed human bronchial epithelial cells. AB - Radon and its progeny were confirmed to be a category I carcinogenic agent. However, the molecular basis underlying carcinogenesis induced by radon has not been fully elucidated. Expression of p53, a key regulator in glycolysis, is known to be decreased in carcinogenesis. The aim of this investigation was to determine changes in energy metabolism mediated by p53-related metabolic pathway using radon-induced transformation of human bronchial epithelial (HBE) cells. HBE cells were exposed to radon for 20 min at a concentration of 20,000 Bq/m(3) and cultured for 3 d, and exposed again at the same concentration and duration. This was repeated 10 times with culture for 35 passages until malignant transformation occurred. During the culturing process, the levels of lactate and lactate dehydrogenase (LDH) and ratio of NAD(+)/NADH gradually increased between passages. Between passages 30 and 35, p53 target gene synthesis of cytochrome c oxidase 2 (SCO2), TP53-induced glycolysis, and apoptosis regulator (TIGAR) expression were significantly decreased. Data demonstrated that p53-associated metabolic pathways may be altered in radon-mediated malignant transformation. PMID- 27267827 TI - Traditional Chinese Medicine Formula "Xiaofeng granules" suppressed gouty arthritis animal models and inhibited the proteoglycan degradation on chondrocytes induced by monosodium urate. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xiaofeng Granules (XF) is a kind of granules prepared by the famous traditional Chinese medicine formula for its efficiency in treating gouty diseases. AIM OF THE STUDY: We investigated the relevance between XF that made from Modified simiaowan (MSW) as the anti-gouty arthritis drugs and protective mechanisms for cartilage matrix in order to provide the evidence for new drug application. MATERIALS AND METHODS: In the present study, we evaluated the anti-gouty arthritis activity of XF in rats and rabbits models induced by MSU together with chondrocytes focusing on the link to proteoglycan degradation in vitro studies. RESULTS: The results demonstrated that XF significantly reduced the swelling rate and attenuated the pathological changes in joints. The XF containing serum were used medicated serum in cellular experiments. The in vitro data were in accordance with the in vivo results, showing that the constituents in XF-containing serum had obvious inhibitory effects on the activation of pro inflammatory mediators in chondrocytes. Moreover, XF-containing serum substantially inhibited MSU-induced expression of glycosaminoglycans(GAG) and hydroxyproline(Hyp), and up regulated proteoglycan, which might be associated with the regulation of the balance of MMP-3/TIMP-1and ADAMTS-4/TIMP-3 inchondrocytes. CONCLUSION: In conclusion, XF that made from MSW showed obvious effects on acute gouty arthritis, which also provided an effective protection on cartilage matrix degradation. PMID- 27267828 TI - Pharmacokinetic comparative study of gastrodin after oral administration of Gastrodia elata Bl. extract and its compatibility with the different indigents of Ligusticum chuanxiong Hort. to rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Da Chuan Xiong Decoction Compound preparation (DCXDCP) is a classic TCM formula of an aqueous extract made from Chuanxiong Rhizoma (Ligusticum chuanxiong Hort., umbelliferae) and Tianma Rhizoma (Gastrodia elata Bl., Orchidaceae). Gastrodin (GAS), a bioactive component of tianma, its pharmacokinetic (PK) behavior significantly changed after oral administration of DCXDCP compared with the extract of tianma. However, little is known about how the ingredients of chuanxiong influenced on the PK of GAS. AIM OF THE STUDY: To study the possible PK behavior differences of GAS after individually oral administration of tianma extract and tianma extract mixed with different active ingredients of chuanxiong to rats, as well as explore whether there were some herb-herb interactions. MATERIALS AND METHODS: Different DCXDCP suspensions were prepared by mixing tianma extract with different active ingredients of chuanxiong. The rats were randomly assigned to six groups and were orally treated with different DCXDCP. At different predetermined time points after administration, the concentrations of GAS in the rat plasma were determined using HPLC, and the main PK parameters were investigated. RESULTS: The results showed that tetramethylpyrazine had no significant effects on the PK parameters of GAS (p>0.05), whereas ferulic acid (FA), total phenolic acids and total alkaloids significantly increased AUC0-infinity (p<0.05). In general the observed changes in the PK parameters of GAS in DCXDCP could be closely related to the total phenolic acids and total alkaloids. CONCLUSION: It could be shown that total phenolic acids and total alkaloids present in Ligusticum chuanxiong in addition to other components not tested yet play an important role in affecting the PK of gastrodin in DCXDCP. PMID- 27267829 TI - Crateva adansonii DC, an African ethnomedicinal plant, exerts cytotoxicity in vitro and prevents experimental mammary tumorigenesis in vivo. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Crateva adansonii DC is a plant traditionally used in Cameroon to treat constipation, asthma, snakebites, postmenopausal complaints and cancers. AIM: The anticancer potential of the dichloromethane/methanol extract of C. adansonii stem barks was investigated using human breast cancer cell and 7,12 dimethylbenz(a)anththracene (DMBA) induced mammary tumorigenesis model in rats. MATERIAL AND METHODS: The cytotoxicity of C. adansonii extract was assessed in vitro towards breast carcinoma (MCF-7 and MDA-MB-231) and non-tumoral cell lines (NIH/3T3 and HUVEC) by Alamar Blue assay. Furthermore, in vivo studies were performed on female Wistar rats treated either with C. adansonii extract at a dose of 75 or 300mg/kg body weight or with tamoxifen (3.3mg/kg body weight), starting 1 week prior DMBA treatment and lasted 12 weeks. The investigation focused on tumour burden, tumour DNA fingerprint, morphological, histological, hematological, and biochemical parameters. RESULTS: CC50 values for the in vitro assays were 289ug/mL against MCF-7 cells and >500ug/mL in others cells, leading to a selectivity index >=1.73. C. adansonii extract significantly (p<0.001) revealed in vivo the reduction of the cumulative tumour yield (87.23%), total tumour burden (88.64%), average tumour weight (71.11%) and tumour volume (78.07%) at the dose of 75mg/kg as compared to DMBA control group. A weak effect was also observed at 300mg/kg. This extract showed a moderate hyperplasia at the dose of 75mg/kg while at 300mg/kg no significant change was noted as compared to DMBA group. It protected rats from the DNA alteration induced by DMBA and increased antioxydant enzymes activities in mammary gland tissue homogenates. In addition, Ultra-High Performance Liquid Chromatography/ESI-QTOF-Mass Spectrometry analysis of C. adansonii extract detected structure-related of many well-known anticancer agents such as flavane gallate, flavonol, phenylpropanoids, sesquiterpene derivatives, gallotannins and lignans. The LD50 of C. adansonii was estimated to be greater than 5000mg/kg. CONCLUSIONS: These aforementioned results suggest that the C. adansonii extract may possess antitumor constituents, which could combat breast cancer and prevent chemically-induced breast cancer in rats. PMID- 27267830 TI - Antibacterial activities of the methanol extracts, fractions and compounds from Harungana madagascariensis Lam. ex Poir. (Hypericaceae). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Harungana madagascariensis Lam. ex Poir. (Hypericaceae) is used in folk medicine to treat a variety of human ailments, mainly antibacterial, antifungal, antiviral and viral infections. In the present study, the methanol extract from the leaves (HML) and bark (HMB) of this plant as well as fractions (HMBa-c), sub-fractions (HMBa1-5) and compounds isolated from HMBa and HMBb namely betulinic acid (1), madagascin (2), ferruginin A (3) and Kaempferol-3-O-beta-d-glucopyranoside (4) were tested for their antimicrobial activities against a panel of 28 g-negative bacteria including multidrug resistant (MDR) phenotypes. MATERIALS AND METHODS: The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the bark extract whilst the chemical structures of compounds were determined using spectroscopic techniques. RESULTS: Crude extract HMB together with fraction HMBa and sub-fraction HMBa3 were active on the 28 tested bacterial strains. HML as well as fractions HMBb, HMBc and sub-fractions HMBa1, HMBa2, HMBa4 and HMBa5 were selectively active. MIC values below or equal to 1024ug/mL were recorded with these samples on 92.9% (for HML and HMBa 4), 82.1% (for HMBb), 78.6% (for HMBa2), 50.0% (for HMBa5) and 42.9% (for HMBc) tested bacteria. For crude material, the lowest MIC value below 8ug/mL was obtained with HMB against Escherichia coli ATCC10536 and W3110 strains, and with sub-fraction HMBa3 against Klebsiella pneumoniae K2 strains. MIC values below 10ug/mL were recorded with compound 3 against E. coli ATCC10536, Enterobacter aerogenes ATCC13048 and EA294, Pseudomonas aeruginosa PA01, K. pneumoniae K2 and Kp55 and Enterobacter cloacae BM67. CONCLUSIONS: Harungana madagascariensis is a potential source of antimicrobial drugs to fight against MDR bacteria. The anthranol 3 is the main antibacterial constituents of the bark of the plant. HMB and compound 3 deserve further investigations to develop natural drug to combat Gram-negative bacteria and otherwise MDR phenotypes. PMID- 27267831 TI - The ethanolic extract of the Eclipta prostrata L. ameliorates the cognitive impairment in mice induced by scopolamine. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata L. (Asteraceae) has been prescribed for whole body nourishment and nervine tonic in Asia. However, the effects of E. prostrata in learning and memory have not been fully explored. AIM OF THE STUDY: To scientifically elucidate the effects of E. prostrata on cognitive functions, we examined whether E. prostrata could ameliorate a cholinergic blockade-induced memory impairment, and we also investigated the effects of E. prostrata on the synaptic plasticity in the hippocampus. MATERIALS AND METHODS: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. The anti-amnesic effects of the ethanolic extract of Eclipta prostrata L. (EEEP) were measured in mice by the passive avoidance, Y maze and Morris water maze tasks. To test the effects of EEEP on synaptic plasticity, we measured long-term potentiation (LTP) in the hippocampus. We also studied several signaling molecules related to learning and memory, such as phosphorylated protein kinase B (Akt) or phosphorylated glycogen synthase kinase 3beta (GSK-3beta). RESULTS: In the passive avoidance task, EEEP (50 or 100mg/kg, p.o.) significantly ameliorated the shortened step-through latency induced by scopolamine. EEEP (100mg/kg, p.o.) also showed significant increase in alternation behavior during the Y-maze task. In the Morris water maze task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by EEEP (50 or 100mg/kg, p.o.). Moreover, EEEP (100MUg/ml) significantly enhanced hippocampal LTP without affecting basal synaptic transmission. The administration of EEEP (100mg/kg) increased the phosphorylation levels of Akt and GSK-3beta in the hippocampal region. CONCLUSION: These results suggest that EEEP has memory-ameliorating activity against scopolamine-induced cognitive impairment and facilitates LTP in the hippocampus. This could be, at least in part, mediated by the activation of the Akt-GSK-3beta signaling pathway. PMID- 27267832 TI - A Preoperative Measurement of Serum MicroRNA-125b May Predict the Presence of Microvascular Invasion in Hepatocellular Carcinomas Patients. AB - The high recurrence rate remains a major problem that strongly influenced the prognosis of hepatocellular carcinoma (HCC) patients who received hepatectomy. The presence of microvascular invasion (MVI) is regarded as the most important risk factor that contributes to the postoperative recurrence. Our previous study has hinted that serum microRNA-125b (miR-125b) was associated with MVI. The aim of the present study was to identify whether serum miR-125b can serve as a biomarker to reliably predict microvascular invasion (MVI) preoperatively. MiR 125b was quantified in 108 HCC patients' serum before they received surgery by quantitative real-time PCR (qRT-PCR). Our results revealed that MVI was associated with relapse free survival (RFS) of postoperative HCC patients; surgical margin width was associated with postoperative RFS in MVI present patients, but not in the patients without MVI. Multivariate analysis revealed that miR-125b, tumor size and AFP were the independent predictive factors associated with MVI in this cohort (P = .001, .001, .003, respectively). The probability of the predictive accuracy of miR-125b was 76.95% (51.32% specificity and 87.50% sensitivity), which was almost equal to the classifier established by combination of AFP and tumor size (78.82% probability, 65.63% specificity and 84.21% sensitivity). Furthermore, the combination of tumor size, AFP and miR-125b yielded a ROC curve area of 86.68% (72.37% specificity and 84.38% sensitivity). Our study indicated that serum miR-125b can be used to predict MVI of HCC patients before they received hepatic resection. Therefore, miR-125b can potentially guide individualized treatment, which helps HCC patients, with or without MVI, to benefit from different surgical approach. PMID- 27267833 TI - Genomic Alterations in Biliary Tract Cancer Using Targeted Sequencing. AB - BACKGROUND: Biliary tract cancers (BTCs) are rare and heterogeneous group of tumors classified anatomically into intrahepatic and extrahepatic bile ducts and gallbladder adenocarcinomas. Patient-derived tumor cell (PDC) models with genome analysis can be a valuable platform to develop a method to overcome the clinical barrier on BTCs. MATERIAL AND METHODS: Between January 2012 and June 2015, 40 BTC patients' samples were collected. PDCs were isolated and cultured from surgical specimens, biopsy tissues, or malignant effusions including ascites and pleural fluid. Genome analysis using targeted panel sequencing as well as digital multiplexed gene analysis was applied to PDCs as well as primary tumors. RESULTS: Extrahepatic cholangiocarcinoma (N=15, 37.5%), intrahepatic cholangiocarcinoma (N=10, 25.0%), gallbladder cancer (N=14, 35.0%), and ampulla of Vater cancer (N=1, 2.5%) were included. We identified 15 mutations with diverse genetic alterations in 19 cases of BTC from primary tumor specimens. The most common molecular alterations were in TP53 (8/19, 42.1%), including missense mutations such as C242Y, E285K, G112S, P19T, R148T, R248Q, and R273L. We also detected two NRAS mutations (G12C and Q61L), two KRAS mutations (G12A and G12S), two ERBB2 mutations (V777L and pM774delinsMA) and amplification, and three PIK3CA mutations (N345K, E545K, and E521K). PDC models were successfully established in 27 of 40 samples (67.5%), including 22/24 from body fluids (91.7%) and 5/16 from tissue specimens (31.3%). CONCLUSIONS: PDC models are promising tools for uncovering driver mutations and identifying rational therapeutic strategies in BTC. Application of this model is expected to inform clinical trials of drugs for molecular-based targeted therapy. PMID- 27267834 TI - Scanning Acoustic Microscopy-A Novel Noninvasive Method to Determine Tumor Interstitial Fluid Pressure in a Xenograft Tumor Model. AB - Elevated tumor interstitial fluid pressure (TIFP) is a prominent feature of solid tumors and hampers the transmigration of therapeutic macromolecules, for example, large monoclonal antibodies, from tumor-supplying vessels into the tumor interstitium. TIFP values of up to 40 mm Hg have been measured in experimental solid tumors using two conventional invasive techniques: the wick-in-needle and the micropuncture technique. We propose a novel noninvasive method of determining TIFP via ultrasonic investigation with scanning acoustic microscopy at 30-MHz frequency. In our experimental setup, we observed for the impedance fluctuations in the outer tumor hull of A431-vulva carcinoma-derived tumor xenograft mice. The gain dependence of signal strength was quantified, and the relaxation of tissue was calibrated with simultaneous hydrostatic pressure measurements. Signal patterns from the acoustical images were translated into TIFP curves, and a putative saturation effect was found for tumor pressures larger than 3 mm Hg. This is the first noninvasive approach to determine TIFP values in tumors. This technique can provide a potentially promising noninvasive assessment of TIFP and, therefore, can be used to determine the TIFP before treatment approach as well to measure therapeutic efficacy highlighted by lowered TFP values. PMID- 27267835 TI - Expression of SOCS1 and CXCL12 Proteins in Primary Breast Cancer Are Associated with Presence of Circulating Tumor Cells in Peripheral Blood. AB - Circulating tumor cells (CTCs) are independent prognostic factors in the primary and metastatic breast cancer patients and play crucial role in hematogenous tumor dissemination. The aim of this study was to correlate the presence of CTCs in peripheral blood with the expression of proteins in tumor tissue that have a putative role in regulation of cell growth and metastatic potential. This prospective study included 203 primary breast cancer patients treated by definitive surgery. CTCs were detected by quantitative real-time PCR for the expression of epithelial (CK19) or epithelial-to-mesenchymal transition-inducing transcription factor genes (TWIST1, SNAIL1, SLUG, and ZEB1). Expression of APC, ADAM23, CXCL12, E-cadherin, RASSF1, SYK, TIMP3, BRMS1, and SOCS1 proteins in primary breast tumor tissue was evaluated by immunohistochemistry. CTCs with epithelial markers were found in 17 (9.2%) patients. Their occurrence was associated with inhibition of SOCS1 expression (odds ratio [OR] = 0.07; 95% confidence interval [CI], 0.03-0.13; P < .001). CTCs with positive epithelial-to mesenchymal transition markers were detected in 30 (15.8%) patients; however, no association with analyzed protein expressions was found. Overall, CTCs were detected in 44 (22.9%) patients. Presence of any CTC marker was significantly associated with positive CXCL12 expression (OR = 3.08; 95% CI, 1.15-8.26; P = .025) and lack of SOCS1 expression (OR = 0.10; 95% CI, 0.04-0.25; P < .001) in patient's tumor tissues. As both CXCL12 and SOCS1 proteins are involved in cytokine signaling, our results provide support for the hypothesis that aberrant signaling cross talk between cytokine and chemokine responses could have an important role in hematogenous dissemination of tumor cells in breast cancer. PMID- 27267836 TI - Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer. AB - Phosphoglycerate dehydrogenase (PHGDH) plays an essential role in cancer-specific metabolic reprogramming. It has been reported as a putative metabolic oncogene in several types of human malignant tumors, such as breast cancer and melanoma. To date, PHGDH expression in colorectal cancer (CRC) as well as its association with clinicopathological characteristics and prognostic implication remain undetermined. In this study, we determined the PHGDH protein expression using tissue microarray immunohistochemistry (TMA-IHC) on 193 pairs of formalin-fixed, paraffin-embedded specimens of CRC and adjacent tissues, 25 chronic colitis, 41 low-, and 19 high-grade intraepithelial neoplasia specimens, and we also determined PHGDH mRNA level using quantitative reverse transcription PCR (qRT PCR) on additional 23 pairs of fresh CRC tissues and adjacent tissues. We found that both PHGDH mRNA and protein was highly expressed in tumor tissues in comparison with matched adjacent non-tumor tissues, and high PHGDH protein expression was correlated with advanced TNM stage (P = .038) and larger tumor (P = .001). Multivariate Cox regression analysis showed that PHGDH protein expression (HR = 2.285, 95% CI = 1.18 to 4.41, P = .014), tumor differentiation (HR = .307, 95% CI = .154 to 0.609, P = .001), and TNM stage (HR = 1.791, 95% CI = 1.125 to 2.85, P = .014) were independent prognostic factors in CRC. Kaplan Meier survival curves and log rank test showed that high PHGDH protein expression contributed to poor outcome in CRC patients (P < .001). In conclusion, these results suggest that assessment of PHGDH expression could be useful in identifying a high-risk subgroup of CRC. PMID- 27267837 TI - BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells. AB - BACKGROUND: Although pazopanib treatment has become the standard chemotherapy in salvage setting for metastatic sarcoma patients, most patients progress after pazopanib treatment in 4 to 6 months. After failure to pazopanib, patients have limited options for treatment. Therefore, subsequent therapy in patients who failed to pazopanib is urgently needed and the use of patient derived cells or patient derived tumors for accompanying testing with various pharmacological inhibitors could offer additional treatment options for these patients. METHODS: Patient derived tumor cells were collected from ascites at the time of progression to pazopanib and a 13-drug panel was tested for drug sensitivity. We confirmed the results using in vitro cell viability assay and immunoblot assay. We also performed the genomic profiling of PDX model. RESULTS: The growth of patient derived tumor cells was significantly reduced by exposure to 1.0 MUM AZD2014 compared with control (control versus AZD2014, mean growth = 100.0% vs 16.04%, difference = 83.96%, 95% CI = 70.01% to 97.92%, P = .0435). Similarly, 1.0 MUM BEZ235 profoundly inhibited tumor cell growth in vitro when compared to control (control versus BEZ235, mean growth = 100.0% vs 7.308%, difference = 92.69%, 95% CI = 78.87% to 106.5%, P < .0001). Despite the presence of CDK4 amplification in the patient-derived tumor cells, LEE011 did not considerably inhibit cell proliferation when compared with control (control vs LEE011, mean growth = 100.0% vs 80.23%, difference = 19.77%, 95% CI = 1.828% to 37.72%, P = .0377). The immunoblot analysis showed that BEZ235 treatment decreased pAKT, pmTOR and pERK whereas AZD2014 decreased only pmTOR. CONCLUSION: Taken together, upregulation of mTOR/AKT pathway in sarcoma patient derived cells was considerably inhibited by the treatment of AZD2014 and BEZ235 with downregulation of AKT pathway (greater extent for BEZ235). These molecules may be considered as treatment option in STS patient who have failed to pazopanib in the context of clinical trials. PMID- 27267838 TI - Rapid Cancer Fluorescence Imaging Using A gamma-Glutamyltranspeptidase-Specific Probe For Primary Lung Cancer. AB - BACKGROUND: We set out to examine the activity of gamma-glutamyltranspeptidase (GGT) in lung cancer and the validity of gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) for intraoperative imaging of primary lung cancer. METHODS: GGT activities and mRNA expression levels of GGT1 (one of the GGT subtypes) in five human lung cancer cell lines were examined by fluorescence imaging and quantitative reverse transcription polymerase chain reaction. In vivo imaging of an orthotopic A549 xenograft model in nude mice was performed to confirm its applicability to intraoperative imaging. Furthermore, ex vivo imaging of 73 specimens from lung cancer patients were performed and analyzed to calculate the sensitivity/specificity of gGlu-HMRG for lung cancer diagnosis. RESULTS: GGT activities and mRNA expression levels of GGT1 are diverse depending on cell type; A549, H441, and H460 showed relatively high GGT activities and expression levels, whereas H82 and H226 showed lower values. In the in vivo mouse model study, tiny pleural dissemination and hilar/mediastinal lymph node metastasis (less than 1 mm in diameter) were clearly detected 15 minutes after topical application of gGlu HMRG. In the ex vivo study of specimens from patients, the sensitivity and specificity of gGlu-HMRG were calculated to be 43.8% (32/73) and 84.9% (62/73), respectively. When limited to female patients, never smokers, and adenocarcinomas, these values were 78.9% (15/19) and 73.7% (14/19), respectively. CONCLUSIONS: Although GGT activity of lung cancer cells vary, gGlu-HMRG can serve as an intraoperative imaging tool to detect small foci of lung cancer when such cells have sufficient GGT activity. PMID- 27267839 TI - Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma. AB - INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases. PMID- 27267840 TI - Evaluating Changes to Blood-Brain Barrier Integrity in Brain Metastasis over Time and after Radiation Treatment. AB - INTRODUCTION: The incidence of brain metastasis due to breast cancer is increasing, and prognosis is poor. Treatment is challenging because the blood brain barrier (BBB) limits efficacy of systemic therapies. In this work, we develop a clinically relevant whole brain radiotherapy (WBRT) plan to investigate the impact of radiation on brain metastasis development and BBB permeability in a murine model. We hypothesize that radiotherapy will decrease tumor burden and increase tumor permeability, which could offer a mechanism to increase drug uptake in brain metastases. METHODS: Contrast-enhanced magnetic resonance imaging (MRI) and high-resolution anatomical MRI were used to evaluate BBB integrity associated with brain metastases due to breast cancer in the MDA-MB-231-BR-HER2 model during their natural development. Novel image-guided microirradiation technology was employed to develop WBRT treatment plans and to investigate if this altered brain metastatic growth or permeability. Histology and immunohistochemistry were performed on whole brain slices corresponding with MRI to validate and further investigate radiological findings. RESULTS: Herein, we show successful implementation of microirradiation technology that can deliver WBRT to small animals. We further report that WBRT following diagnosis of brain metastasis can mitigate, but not eliminate, tumor growth in the MDA-MB-231-BR HER2 model. Moreover, radiotherapy did not impact BBB permeability associated with metastases. CONCLUSIONS: Clinically relevant WBRT is not curative when delivered after MRI-detectable tumors have developed in this model. A dose of 20 Gy in 2 fractions was not sufficient to increase tumor permeability such that it could be used as a method to increase systemic drug uptake in brain metastasis. PMID- 27267842 TI - miR-1207-3p Is a Novel Prognostic Biomarker of Prostate Cancer. AB - MicroRNAs (miRNAs) have been found to be dysregulated in prostate cancer (PCa). In this study, we investigated if miR-1207-3p is capable of distinguishing between indolent and aggressive PCa and if it contributes to explaining the disproportionate aggressiveness of PCa in men of African ancestry (moAA). A total of 404 patients with primary adenocarcinoma of the prostate were recruited between 1988 and 2003 at the Moffitt Cancer Center, Tampa, FL, USA. Patient clinicopathological features and demographic characteristics such as race were identified. RNA samples from 404 postprostatectomy prostate tumor tissue samples were analyzed by real-time quantitative reverse transcription polymerase chain reaction for the mRNA expression of miR-1207-3p. miR-1207-3p expression in PCa that resulted in overall death or PCa-specific death is significantly higher than in PCa cases that did not. The same positive correlation holds true for other clinical characteristics such as biochemical recurrence, Gleason score, clinical stage, and prostate-specific antigen level. Furthermore, miR-1207-3p expression was significantly less in moAA in comparison to Caucasian men. We also evaluated whether miR-1207-3p is associated with clinical outcomes adjusted for age at diagnosis and tumor stage in the modeling. Using competing risk regression, the PCa patients with a high miR-1207-3p expression (>=6 vs 3) had a high risk to develop PCa recurrence (hazard rate = 2.5, P < .001) adjusting for age at diagnosis and tumor stage. In conclusion, miR-1207-3p is a promising novel prognostic biomarker for PCa. Furthermore, miR-1207-3p may also be important in explaining the disproportionate aggressiveness of PCa in moAA. PMID- 27267841 TI - Magnetic Resonance Imaging Identifies Differential Response to Pro-Oxidant Chemotherapy in a Xenograft Model. AB - Induction of oxidative stress is a key component of cancer therapy. Pro-oxidant drugs have been demonstrated to enhance the efficacy of radiotherapy and chemotherapy. An emerging concept is that therapeutic outcomes are dictated by the differential redox buffering reserve in subpopulations of malignant cells, indicating the need for noninvasive biomarkers of tumor redox that can be used for dose identification and response assessment in a longitudinal setting. Magnetic resonance imaging (MRI) enhanced with the thiol-binding contrast agent Gd-LC6-SH, and hemodynamic response imaging (HRI) in combination with hypercapnia and hyperoxia were investigated as biomarkers of the pharmacodynamics of the small molecule pro-oxidant imexon (IMX). Human multiple myeloma cell lines 8226/S and an IMX-resistant variant, 8226/IM10, were established as contralateral tumors in SCID mice. T1slope, an MRI measure of the washout rate of Gd-LC6-SH, was significantly lower post-IMX therapy in 8226/S tumors compared with vehicle controls, indicating treatment-related oxidization of the tumor microenvironment, which was confirmed by analysis of tumor tissue for thiols. T1slope and ex vivo assays for thiols both indicated a more reduced microenvironment in 8226/IM10 tumors following IMX therapy. HRI with hypercapnia challenge revealed IMX inhibition of vascular dilation in 8226/S tumors but not 8226/IM10 tumors, consistent with decreased immunohistochemical staining for smooth muscle actin in treated 8226/S tumors. MRI enhanced with Gd-LC6-SH, and HRI coupled with a hypercapnic challenge provide noninvasive biomarkers of tumor response to the redox modulator imexon. PMID- 27267843 TI - Application of a Serum Protein Signature for Pancreatic Cancer to Separate Cases from Controls in a Pancreatic Surveillance Cohort. AB - BACKGROUND: Pancreatic cancer (PC) surveillance is currently offered to individuals with a genetic predisposition to PC, but routinely used radiological screening modalities are not entirely reliable in detecting early-stage PC or its precursor lesions. We recently identified a discriminating PC biomarker signature in a sporadic patient cohort. In this study, we investigated if protein profiling can accurately distinguish PC from non-PC in a pancreatic surveillance cohort of genetically predisposed individuals. METHODS: Serum samples of 66 individuals with a CDKN2A germline mutation who participated in the pancreatic surveillance program (5 cases, 61 controls) were obtained following a standardized protocol. After sample clean-up, peptide and protein profiles were obtained on an ultrahigh resolution matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry platform. A discriminant score for each sample was calculated with a previously designed prediction rule, and the median discriminant scores of cases and controls were compared. Individuals with precursor lesions of PC (n = 4) and individuals with a recent diagnosis of melanoma (n = 4) were also separately considered. RESULTS: Cases had a higher median discriminant score than controls (0.26 vs 0.016; P = .001). The only individual with pathologically confirmed precursor lesions of PC could also be clearly distinguished from controls, and having a (recent) medical history of melanoma did not influence the protein signatures. CONCLUSIONS: Peptide and protein signatures are able to accurately distinguish PC cases from controls in a pancreatic surveillance setting. Mass spectrometry-based protein profiling therefore seems to be a promising candidate for implementation in the pancreatic surveillance program as an additional screening modality. PMID- 27267844 TI - Dasatinib-Induced CMV Hepatitis in an Immunocompetent Patient: A Rare Complication of a Common Drug. AB - Dasatinib is a common anticancer drug used in the treatment of leukemia. Several side effects have been reported, the most common being myelosuppression, diarrhea, edema, and nausea. Three papers have been published reporting hepatic side effects of dasatinib treatment. A rare side effect of dasatinib treatment is reactivation of latent cytomegalovirus (CMV) infection. Never before has dasatinib therapy shown to be the cause of CMV hepatitis in an immunocompetent patient. We present a case of an immunocompetent patient who was treated with the standard dose of dasatinib therapy and subsequently developed CMV hepatitis. Well known side effects of dasatinib therapy are understood and documented; unknown adverse drug reactions can occur and should be monitored for. This is a significant finding given the high rate of CMV seropositivity in the general population. PMID- 27267845 TI - Detection of Biomarkers with Solid-Phase Proximity Ligation Assay in Patients with Colorectal Cancer. AB - BACKGROUND: In the search for prognostic biomarkers, a significant amount of precious biobanked blood samples is needed for conventional analyses. Solid-phase proximity ligation assay (SP-PLA) is an analytic method with the ability to analyze many proteins at the same time in small amounts of plasma. The aim of this study was to explore the potential use of SP-PLA for biomarker validation in patients with colorectal cancer (CRC). MATERIAL AND METHODS: Plasma samples from patients with stage I to IV CRC, with (n = 31) and without (n = 29) disease dissemination at diagnosis or later, were analyzed with SP-PLA using 35 antibodies targeting an equal number of proteins in 5-MUl plasma samples. Carcinoembryonic antigen (CEA), analyzed earlier in this cohort using a different technology, was used as a reference. RESULTS: A total of 21 of the 35 investigated proteins were detectable with SP-PLA. Patients in stage II to III with disseminated disease had lower plasma concentrations of HCC-4 (P = .025). Low plasma levels of tissue inhibitor of metalloproteinases-1 were seen in patients with disseminated disease stage II (P = .003). The level of CEA was higher in patients with disease dissemination compared with those without (P = .007). CONCLUSION: SP-PLA has the ability to analyze many protein markers simultaneously in a small amount of blood. However, none of the markers selected for the present SP-PLA analyses gave better prognostic information than CEA. PMID- 27267846 TI - A Prognostic Model in Metastatic or Recurrent Gastric Cancer Patients with Good Performance Status Who Received First-Line Chemotherapy. AB - PURPOSE: Good performance status is widely known as a superior prognostic predictor. However, some patients have large survival differences despite having good performance status that are influenced by certain prognostic factors. The purpose of this study was to explore baseline host- or tumor-related factors and to establish a prognostic model for metastatic or recurrent gastric cancer patients with good performance status who received first-line chemotherapy. METHODS: A total of 310 metastatic or recurrent gastric cancer patients with good performance status who received first-line chemotherapy were enrolled. Prognostic significance was determined using multivariate Cox regression analysis. Incorporating all pretreatment indicators, a prognostic model was established. Overall survival outcomes were compared with different risk groups using the Kaplan-Meier method and log-rank test. RESULTS: In multivariate analysis, no previous gastrectomy [hazard ratio (HR) = 1.42; 95% confidence interval (CI) = 1.08-1.85], number of distant metastatic sites (HR = 1.47; 95% CI = 1.11-1.96), bone metastasis (HR = 2.20; 95% CI = 1.16-4.18), liver metastasis (HR = 1.77; 95% CI = 1.31-2.39), and an elevated neutrophil lymphocyte ratio (HR = 1.37; 95% CI = 1.04-1.79) were independent prognostic factors of overall survival. Patients were categorized into three risk groups according to their risk scores. Median survival times for the low-risk (0 point), intermediate-risk (1-3 points), and high-risk (>=4 points) groups were 19.7, 10.7 and 5.1 months, respectively (P < .001). CONCLUSIONS: A prognostic model was developed that could facilitate risk stratification for metastatic or recurrent gastric cancer patients with good performance status who received first-line chemotherapy to help clinicians choose an applicable treatment based on the estimated prognosis. PMID- 27267847 TI - The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic Pituitary-Adrenal Axis at Different Levels in Female Rats. AB - Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-gamma protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function. PMID- 27267848 TI - Role of mTOR Inhibitors in Growth Hormone-Producing Pituitary Adenomas Harboring Different FGFR4 Genotypes. AB - Pituitary adenomas (PAs) are common intracranial lesions. Available medical therapies are limited in PAs, and therefore, it is essential to identify treatments that control PA growth when surgery is not an option. Fibroblast growth factor 4 is implicated in PA pathogenesis; therefore, in this study, we used an isogenic mammosomatotroph cell line (GH4C1) harboring different fibroblast growth factor receptor (FGFR)-4 genotypes to establish and characterize intracranial xenograft mouse models that can be used for preclinical drug testing. We show that proliferating GH4C1 tumors have an average latency of 3 weeks to form. Histological analysis revealed that prototypic FGFR4 (G388) tumors express increased prolactin and less GH, whereas tumors possessing the polymorphic variant of FGFR4 (R388) express increased GH relative to prolactin. All tumors show abundant mammalian target of rapamycin (mTOR) signaling as confirmed using phosphorylated (p)-S6 and p-4E-binding protein 1 as downstream regulators of this pathway. We subsequently demonstrate that the mTOR inhibitor RAD001 decreases tumor growth rate and reduces p-S6 but not p-4E-binding protein 1 activation, regardless of FGFR4 status. More importantly, GH activity was significantly reduced after mTOR inhibition in the R388 polymorphic variant tumors. This reduction was also associated with a concomitant reduction in serum IGF-1 levels in the R388 group. In summary, we demonstrate that the GH4C1 FGFR polymorphic xenograft is a useful model for examining PAs. Furthermore, we show that RAD001 can efficiently reduce tumor growth rate by a reduction in mTOR signaling and more importantly results in control of GH expression and IGF-1 secretion, providing further support for using mTOR inhibitors in PA patients, in particular GH-producing adenomas. PMID- 27267849 TI - CD103 and Intratumoral Immune Response in Breast Cancer. AB - PURPOSE: CD103 is expressed in several immune cell types but in the context of the intratumoral immune response may be most important as a marker of antigen activated CD8 T cells. METHODS: We have examined the prognostic significance of CD103 TILs in breast cancer by IHC in a cohort of 424 breast cancer patients. RESULTS: CD103 TILs were present in all subtypes but were more abundant in ER negative tumors where CD103 TILs were preferentially localized to the intraepithelial compartment. CD103 was associated with tumor size, tumor grade, and ER/PR status (P < 0.05). CD103 TIL density and the epithelial to stromal ratio was highest in the basal-like tumors. Intraepithelial CD103 but not intrastromal CD103 was associated with better relapse-free and overall survival in basal-like subtype tumors [HR = 0.28; 95% confidence interval (CI), 0.17-0.72; P = 0.0047 and HR = 0.25; 95% CI, 0.17-0.66; P = 0.0017, respectively). CD8 status showed similar but less significant associations, but the combination of dual CD103+CD8+ TIL status was the most strongly prognostic combination for relapse-free and overall survival (HR = 0.10; 95% CI, 0.07-0.62; P = 0.006 and HR = 0.09; 95% CI, 0.07-0.57; P = 0.003, respectively). CONCLUSIONS: CD103 TILs are indicative of a good prognosis specifically within the basal-like subtype of breast cancer. Clin Cancer Res; 22(24); 6290-7. (c)2016 AACR. PMID- 27267850 TI - A Novel HSP90 Inhibitor-Drug Conjugate to SN38 Is Highly Effective in Small Cell Lung Cancer. AB - PURPOSE: Small cell lung cancer (SCLC) is a highly aggressive disease representing 12% to 13% of total lung cancers, with median survival of <2 years. No targeted therapies have proven effective in SCLC. Although most patients respond initially to cytotoxic chemotherapies, resistance rapidly emerges, response to second-line agents is limited, and dose-limiting toxicities (DLT) are a major issue. This study performs preclinical evaluation of a new compound, STA 8666, in SCLC. EXPERIMENTAL DESIGN: To avoid DLT for useful cytotoxic agents, the recently developed drug STA-8666 combines a chemical moiety targeting active HSP90 (concentrated in tumors) fused via cleavable linker to SN38, the active metabolite of irinotecan. We compare potency and mechanism of action of STA-8666 and irinotecan in vitro and in vivo RESULTS: In two SCLC xenograft and patient derived xenograft models, STA-8666 was tolerated without side effects up to 150 mg/kg. At this dose, STA-8666 controlled or eliminated established tumors whether used in a first-line setting or in tumors that had progressed following treatment on standard first- and second-line agents for SCLC. At 50 mg/kg, STA-8666 strongly enhanced the action of carboplatin. Pharmacokinetic profiling confirmed durable STA-8666 exposure in tumors compared with irinotecan. STA-8666 induced a more rapid, robust, and stable induction of cell-cycle arrest, expression of signaling proteins associated with DNA damage and cell-cycle checkpoints, and apoptosis in vitro and in vivo, in comparison with irinotecan. CONCLUSIONS: Together, these results strongly support clinical development of STA-8666 for use in the first- or second-line setting for SCLC. Clin Cancer Res; 22(20); 5120-9. (c)2016 AACR. PMID- 27267851 TI - SNP rs16906252C>T Is an Expression and Methylation Quantitative Trait Locus Associated with an Increased Risk of Developing MGMT-Methylated Colorectal Cancer. AB - PURPOSE: Methylation of the MGMT promoter is the major cause of O6-methylguanine methyltransferase deficiency in cancer and has been associated with the T variant of the promoter enhancer SNP rs16906252C>T. We sought evidence for an association between the rs16906252C>T genotype and increased risk of developing a subtype of colorectal cancer featuring MGMT methylation, mediated by genotype-dependent epigenetic silencing within normal tissues. EXPERIMENTAL DESIGN: By applying a molecular pathologic epidemiology case-control study design, associations between rs16906252C>T and risk for colorectal cancer overall, and colorectal cancer stratified by MGMT methylation status, were estimated using multinomial logistic regression in two independent retrospective series of colorectal cancer cases and controls. The test sample comprised 1,054 colorectal cancer cases and 451 controls from Sydney, Australia. The validation sample comprised 612 colorectal cancer cases and 245 controls from the Australasian Colon Cancer Family Registry (ACCFR). To determine whether rs16906252C>T was linked to a constitutively altered epigenetic state, quantitative allelic expression and methylation analyses were performed in normal tissues. RESULTS: An association between rs16906252C>T and increased risk of developing MGMT-methylated colorectal cancer in the Sydney sample was observed [OR, 3.3; 95% confidence interval (CI), 2.0 5.3; P < 0.0001], which was replicated in the ACCFR sample (OR, 4.0; 95% CI, 2.4 6.8; P < 0.0001). The T allele demonstrated about 2.5-fold reduced transcription in normal colorectal mucosa from cases and controls and was selectively methylated in a minority of normal cells, indicating that rs16906252C>T represents an expression and methylation quantitative trait locus. CONCLUSIONS: We provide evidence that rs16906252C>T is associated with elevated risk for MGMT methylated colorectal cancer, likely mediated by constitutive epigenetic repression of the T allele. Clin Cancer Res; 22(24); 6266-77. (c)2016 AACR. PMID- 27267852 TI - Targeting Estrogen Receptor Signaling with Fulvestrant Enhances Immune and Chemotherapy-Mediated Cytotoxicity of Human Lung Cancer. AB - PURPOSE: The conversion of tumor cells from an epithelial to a mesenchymal-like phenotype, via a process designated as the epithelial-mesenchymal transition (EMT), is known to mediate tumor resistance to a variety of cell death inducers, including cytotoxic effector immune cells. The goal of this study was to identify and potentially repurpose FDA-approved compounds capable of reducing mesenchymal features of human lung carcinoma cells, which could be used in combination with immunotherapies or chemotherapeutic strategies to improve clinical responses. EXPERIMENTAL DESIGN: In the current report, we have utilized a quantitative high throughput screening (qHTS) of a pharmaceutical collection of more than 2,000 compounds to identify clinically approved drugs capable of augmenting the sensitivity of mesenchymal-like, lung cancer cells to immune- and chemotherapy mediated lysis, both in vitro and in vivo RESULTS: The estrogen receptor antagonist fulvestrant was shown to reduce mesenchymal features of lung carcinoma cells, resulting in tumor sensitization to the cytotoxic effect of antigen specific T cells, natural killer (NK) effector cells, and chemotherapy both in vivo and in vitro CONCLUSIONS: To our knowledge, this is the first report defining a potential role for estrogenic signaling in promoting tumor resistance to immune-mediated cytotoxicity and chemotherapy in lung cancer. Our data demonstrate a robust association between the acquisition of mesenchymal attributes, therapeutic resistance of lung carcinoma cells, and the expression of estrogen receptor 1 (ESR1), supporting further investigations on the role of estrogen signaling in lung cancer progression via the induction of EMT. Clin Cancer Res; 22(24); 6204-16. (c)2016 AACR. PMID- 27267853 TI - Recurrent Mutations in the MTOR Regulator RRAGC in Follicular Lymphoma. AB - PURPOSE: This study was performed to further our understanding of the biological and genetic basis of follicular lymphoma and to identify potential novel therapy targets. EXPERIMENTAL DESIGN: We analyzed previously generated whole exome sequencing data of 23 follicular lymphoma cases and one transformed follicular lymphoma case and expanded findings to a combined total of 125 follicular lymphoma/3 transformed follicular lymphoma. We modeled the three-dimensional location of RRAGC-associated hotspot mutations. We performed functional studies on novel RRAGC mutants in stable retrovirally transduced HEK293T cells, stable lentivirally transduced lymphoma cell lines, and in Saccharomyces cerevisiae RESULTS: We report recurrent mutations, including multiple amino acid hotspots, in the small G-protein RRAGC, which is part of a protein complex that signals intracellular amino acid concentrations to MTOR, in 9.4% of follicular lymphoma cases. Mutations in RRAGC distinctly clustered on one protein surface area surrounding the GTP/GDP-binding sites. Mutated RRAGC proteins demonstrated increased binding to RPTOR (raptor) and substantially decreased interactions with the product of the tumor suppressor gene FLCN (folliculin). In stable retrovirally transfected 293T cells, cultured in the presence or absence of leucine, multiple RRAGC mutations demonstrated elevated MTOR activation as evidenced by increased RPS6KB/S6-kinase phosphorylation. Similar activation phenotypes were uncovered in yeast engineered to express mutations in the RRAGC homolog Gtr2 and in multiple lymphoma cell lines expressing HA-tagged RRAGC mutant proteins. CONCLUSIONS: Our discovery of activating mutations in RRAGC in approximately 10% of follicular lymphoma provides the mechanistic rationale to study mutational MTOR activation and MTOR inhibition as a potential novel actionable therapeutic target in follicular lymphoma. Clin Cancer Res; 22(21); 5383-93. (c)2016 AACR. PMID- 27267854 TI - Biomarker Associations with Efficacy of Abiraterone Acetate and Exemestane in Postmenopausal Patients with Estrogen Receptor-Positive Metastatic Breast Cancer. AB - PURPOSE: Abiraterone may suppress androgens that stimulate breast cancer growth. We conducted a biomarker analysis of circulating tumor cells (CTCs), formalin fixed paraffin-embedded tissues (FFPETs), and serum samples from postmenopausal estrogen receptor (ER)+ breast cancer patients to identify subgroups with differential abiraterone sensitivity. METHODS: Patients (randomized 1:1:1) were treated with 1,000 mg/d abiraterone acetate + 5 mg/d prednisone (AA), AA + 25 mg/d exemestane (AAE), or exemestane. The biomarker population included treated patients (n = 293). The CTC population included patients with >=3 baseline CTCs (n = 104). Biomarker [e.g., androgen receptor (AR), ER, Ki-67, CYP17] expression was evaluated. Cox regression stratified by prior therapies in the metastatic setting (0/1 vs. 2) and setting of letrozole/anastrozole (adjuvant vs. metastatic) was used to assess biomarker associations with progression-free survival (PFS). RESULTS: Serum testosterone and estrogen levels were lowered and progesterone increased with AA. Baseline AR or ER expression was not associated with PFS in CTCs or FFPETs for AAE versus exemestane, but dual positivity of AR and ER expression was associated with improved PFS [HR, 0.41; 95% confidence interval (CI), 0.16-1.07; P = 0.070]. For AR expression in FFPETs obtained <1 year prior to first dose (n = 67), a trend for improved PFS was noted for AAE versus exemestane (HR, 0.56; 95% CI, 0.24-1.33; P = 0.19). CONCLUSIONS: An AA pharmacodynamic effect was shown by decreased serum androgen and estrogen levels and increased progesterone. AR and ER dual expression in CTCs and newly obtained FFPETs may predict AA sensitivity. Clin Cancer Res; 22(24); 6002-9. (c)2016 AACR. PMID- 27267857 TI - Potential lipase inhibitors from Chinese medicinal herbs. AB - CONTEXT: Obesity has become a major health concern, and it places both personal and economic burdens on the world's population. Traditional Chinese medicinal herbs are rich source of lead compounds and are possible drug candidates, which may be used to treat this condition. OBJECTIVE: This study screened potent pancreatic lipase inhibitors found in traditional Chinese medicinal herbs for ability to treat obesity. MATERIALS AND METHODS: A porcine pancreatic lipase inhibition assay was established, and the inhibitory activity of 35 traditional Chinese medicinal herbs was evaluated at a concentration of 200 MUg/mL. Two elutions of herbal extracts with strong lipase inhibitory activity were further fractionated by preparative high-performance liquid chromatography into 22 sub fractions each, and these sub-fractions were tested for anti-lipase activity. Sub fractions, which exhibited strong lipase inhibitory activity, were continuously fractionated into individual compounds. Two active compounds with potent anti lipase activity were finally isolated and identified from two traditional Chinese medicinal herbs, respectively. RESULTS: Among 35 traditional Chinese medicinal herbs, the 95% ethanol elutions of Panax notoginseng (Burk.) F.H. Chen (Araliaceae) and Magnolia officinalis Rehd. et Wils (Magnoliaceae) showed strong anti-lipase activity. Two compounds, including 20(S)-ginsenoside Rg3 and honokiol were identified using bioactivity-guided isolation with IC50 = 33.7 and 59.4 MUg/mL, respectively. CONCLUSION: 20(S)-ginsenoside Rg3 and honokiol might be suitable candidates for the treatment of obesity. PMID- 27267855 TI - CD44 Expression Level and Isoform Contributes to Pancreatic Cancer Cell Plasticity, Invasiveness, and Response to Therapy. AB - PURPOSE: A subpopulation of pancreatic ductal adenocarcinoma (PDAC) cells is thought to be inherently resistant to chemotherapy or to give rise to tumor cells that become resistant during treatment. Here we determined the role of CD44 expression and its isoforms as a marker and potential target for tumor cells that give rise to invasive and gemcitabine-resistant tumors. EXPERIMENTAL DESIGN: RT PCR, Western blotting, and DNA sequencing was used to determine CD44 isoform and expression levels. Flow cytometry was used to sort cells on the basis of their CD44 expression level. CD44 expression was knocked down using shRNA. Tumorigenic properties were determined by clonogenic and Matrigel assays, IHC, tumor growth in vivo using luciferase imaging and by tumor weight. RESULTS: We identified an invasive cell population that gives rise to gemcitabine-resistant tumors. These cancer cells express a high level of CD44 standard isoform and have an EMT phenotype (CD44s/EMT). In vivo, CD44s/EMT engraft and expand rapidly and give rise to tumors that express high levels of CD44 isoforms that contain multiple exon variants. CD44low-expressing cells show continued sensitivity to gemcitabine in vivo and knockdown of CD44 in CD44s/EMT cells increases sensitivity to gemcitabine and decreases invasiveness. CONCLUSIONS: PDAC cells expressing high levels of CD44s with a mesenchymal-like phenotype were highly invasive and developed gemcitabine resistance in vivo Thus, initial targeting CD44 or reversing the CD44high phenotype may improve therapeutic response. Clin Cancer Res; 22(22); 5592-604. (c)2016 AACR. PMID- 27267856 TI - An FGFR3 Autocrine Loop Sustains Acquired Resistance to Trastuzumab in Gastric Cancer Patients. AB - PURPOSE: The majority of gastric cancer patients who achieve an initial response to trastuzumab-based regimens develop resistance within 1 year of treatment. This study was aimed at identifying the molecular mechanisms responsible for resistance. EXPERIMENTAL DESIGN: A HER2+-trastuzumab sensitive NCI-N87 gastric cancer orthotopic nude mouse model was treated with trastuzumab until resistance emerged. Differentially expressed transcripts between trastuzumab-resistant and sensitive gastric cancer cell lines were annotated for functional interrelatedness by Ingenuity Pathway Analysis software. Immunohistochemical analyses were performed in pretreatment versus posttreatment biopsies from gastric cancer patients receiving trastuzumab-based treatments. All statistical tests were two-sided. RESULTS: Four NCI-N87 trastuzumab-resistant (N87-TR) cell lines were established. Microarray analysis showed HER2 downregulation, induction of epithelial-to-mesenchymal transition, and indicated fibroblast growth factor receptor 3 (FGFR3) as one of the top upregulated genes in N87-TR cell lines. In vitro, N87-TR cell lines demonstrated a higher sensitivity than did trastuzumab sensitive parental cells to the FGFR3 inhibitor dovitinib, which reduced expression of pAKT, ZEB1, and cell migration. Oral dovitinib significantly (P = 0.0006) reduced tumor burden and prolonged mice survival duration in N87-TR mouse models. A higher expression of FGFR3, phosphorylated AKT, and ZEB1 were observed in biopsies from patients progressing under trastuzumab-based therapies if compared with matched pretreatment biopsies. CONCLUSIONS: This study identified the FGFR3/AKT axis as an escape pathway responsible for trastuzumab resistance in gastric cancer, thus indicating the inhibition of FGFR3 as a potential strategy to modulate this resistance. Clin Cancer Res; 22(24); 6164-75. (c)2016 AACR. PMID- 27267858 TI - Bending the Arc of Exercise and Recreation Technology Toward People With Disabilities. AB - Most of the published research on exercise and disability has focused on short term efficacy studies targeting specific disability groups. These studies often use grant-related or other financial resources to temporarily remove the many barriers that people with physical/mobility disability experience when attempting to become physically active. In this commentary, we explore how technology can be used to promote more sustainable physical activity outcomes in the home and community using a set of 4 overlapping domains: Access, Usability, Adherence, and Health and Function. In addition, we describe how the order in which these domains should be addressed will vary depending on the needs of the target group and the context of their environment. Finally, we provide examples of various types of technologies (eg, hardware and software) that can support the "afterlife" of successful short-term exercise and rehabilitation trials in people with physical/mobility disability who desire to self-manage their own health and maintain a regular and sustainable pattern of physical activity across their life span. PMID- 27267859 TI - Deep Brain Stimulation for Addiction Treatment: Further Considerations on Scientific and Ethical Issues. PMID- 27267860 TI - Transcranial Laser Stimulation as Neuroenhancement for Attention Bias Modification in Adults with Elevated Depression Symptoms. AB - BACKGROUND: Low-level light therapy (LLLT) with transcranial laser is a non invasive form of neuroenhancement shown to regulate neuronal metabolism and cognition. Attention bias modification (ABM) is a cognitive intervention designed to improve depression by decreasing negative attentional bias, but to date its efficacy has been inconclusive. Adjunctive neuroenhancement to augment clinical effectiveness has shown promise, particularly for individuals who respond positively to the primary intervention. OBJECTIVE/HYPOTHESIS: This randomized, sham-controlled proof-of-principle study is the first to test the hypothesis that augmentative LLLT will improve the effects of ABM among adults with elevated symptoms of depression. METHODS: Fifty-one adult participants with elevated symptoms of depression received ABM before and after laser stimulation and were randomized to one of three conditions: right forehead, left forehead, or sham. Participants repeated LLLT two days later and were assessed for depression symptoms one and two weeks later. RESULTS: A significant three-way interaction between LLLT condition, ABM response, and time indicated that right LLLT led to greater symptom improvement among participants whose attention was responsive to ABM (i.e., attention was directed away from negative stimuli). Minimal change in depression was observed in the left and sham LLLT. CONCLUSIONS: The beneficial effects of ABM on depression symptoms may be enhanced when paired with adjunctive interventions such as right prefrontal LLLT; however, cognitive response to ABM likely moderates the impact of neuroenhancement. The results suggest that larger clinical trials examining the efficacy of using photoneuromodulation to augment cognitive training are warranted. PMID- 27267862 TI - Thailandins A and B, New Polyene Macrolactone Compounds Isolated from Actinokineospora bangkokensis Strain 44EHW(T), Possessing Antifungal Activity against Anthracnose Fungi and Pathogenic Yeasts. AB - Two new polyene macrolactone antibiotics, thailandins A, 1, and B, 2, were isolated from the fermentation broth of rhizosphere soil-associated Actinokineospora bangkokensis strain 44EHW(T). The new compounds from this strain were purified using semipreparative HPLC and Sephadex LH-20 gel filtration while following an antifungal activity guided fractionation. Their structures were elucidated through spectroscopic techniques including UV, HR-ESI-MS, and NMR. These compounds demonstrated broad spectrum antifungal activity against fungi causing anthracnose disease (Colletotrichum gloeosporioides DoA d0762, Colletotrichum gloeosporiodes DoA c1060, and Colletotrichum capsici DoA c1511) as well as pathogenic yeasts (Candida albicans MT 2013/1, Candida parasilopsis DKMU 434, and Cryptococcus neoformans MT 2013/2) with minimum inhibitory concentrations ranging between 16 and 32 MUg/mL. This is the first report of polyene antibiotics produced by Actinokineospora species as bioactive compounds against anthracnose fungi and pathogenic yeast strains. PMID- 27267861 TI - Dual Effects of Limbic Seizures on Psychosis-Relevant Behaviors Shown by Nucleus Accumbens Kindling in Rats. AB - BACKGROUND: A paradox in epilepsy and psychiatry is that temporal lobe epilepsy is often predisposed to schizophrenic-like psychosis, whereas convulsive therapy can relieve schizophrenic symptoms. We have previously demonstrated that the nucleus accumbens is a key structure in mediating postictal psychosis induced by a hippocampal electrographic seizure. OBJECTIVE/HYPOTHESIS: The purpose of this study is to test a hypothesis that accumbens kindling cumulating in a single (1 time) or repeated (5-times) convulsive seizures have different effects on animal models of psychosis. METHODS: Electrical stimulation at 60 Hz was applied to nucleus accumbens to evoke afterdischarges until one, or five, convulsive seizures that involved the hind limbs (stage 5 seizures) were attained. Behavioral tests, performed at 3 days after the last seizure, included gating of hippocampal auditory evoked potentials (AEP) and prepulse inhibition to an acoustic startle response (PPI), tested without drug injection or after ketamine (3 mg/kg s.c.) injection, as well as locomotion induced by ketamine or methamphetamine (1 mg/kg i.p.). RESULTS: Compared to non-kindled control rats, 1 time, but not 5-times, convulsive seizures induced PPI deficit and decreased gating of hippocampal AEP, without drug injection. Compared to non-kindled rats, 5-times, but not 1-time, convulsive seizures antagonized ketamine-induced hyperlocomotion, ketamine-induced PPI deficit and AEP gating decrease. However, both 1- and 5-times convulsive seizures significantly enhanced methamphetamine induced locomotion as compared to non-kindled rats. CONCLUSIONS: Accumbens kindling ending with 1 convulsive seizure may induce schizophrenic-like behaviors, while repeated (>=5) convulsive seizures induced by accumbens kindling may have therapeutic effects on dopamine independent psychosis. PMID- 27267863 TI - Melatonin regulates catecholamine biosynthesis by modulating bone morphogenetic protein and glucocorticoid actions. AB - Melatonin is functionally involved in the control of circadian rhythm and hormonal secretion. In the present study, we investigated the roles of melatonin in the interaction of catecholamine synthesis with adrenocortical steroids by focusing on bone morphogenetic protein (BMP)-4 expressed in the adrenal medulla using rat pheochromocytoma PC12 cells. Melatonin treatment significantly reduced the mRNA expression of catecholamine synthases, including the rate-limiting enzyme tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanine decarboxylase and dopamine-beta-hydroxylase expressed in PC12 cells. In accordance with changes in the expression levels of enzymes, dopamine production and cAMP synthesis determined in the culture medium and cell lysate were also suppressed by melatonin. The MT1 receptor, but not the MT2 receptor, was expressed in PC12 cells, and luzindole treatment reversed the inhibitory effect of melatonin on Th expression, suggesting that MT1 is a functional receptor for the control of catecholamine synthesis. Interestingly, melatonin enhanced the inhibitory effect of BMP-4 on Th mRNA expression in PC12 cells. Melatonin treatment accelerated BMP 4-induced phosphorylation of SMAD1/5/8 and transcription of the BMP target gene Id1. Of note, melatonin significantly upregulated Alk2 and Bmpr2 mRNA levels but suppressed inhibitory Smad6/7 expression, leading to the enhancement of SMAD1/5/8 signaling in PC12 cells, while BMP-4 did not affect Mt1 expression. Regarding the interaction with adrenocortical steroids, melatonin preferentially enhanced glucocorticoid-induced Th mRNA through upregulation of the glucocorticoid receptor and downregulation of Bmp4 expression, whereas melatonin repressed Th mRNA expression induced by aldosterone or androgen without affecting expression levels of the receptors for mineralocorticoid and androgen. Collectively, the results indicate that melatonin plays a modulatory role in catecholamine synthesis by cooperating with BMP-4 and glucocorticoid in the adrenal medulla. PMID- 27267864 TI - Composition and Concentration Gradient Induced Structural Transition from Micelles to Vesicles in the Mixed System of Ionic Liquid-Diclofenac Sodium. AB - Catanionic surfactant-hydrotrope mixtures have proven to be a striking alternative to tune microstructures over a wide range of compositions and also to minimize precipitation that is normally observed in catanionic mixtures at an equimolar ratio. These mixtures are supposed to be of great relevance in biological systems when a hydrotrope is a "drug". Keeping this in view, here we report composition- and dilution-induced structural changes in a catanionic mixture comprising ionic liquids (ILs), such as 1-dodecyl-3-methylimidazolium bromide (C12mimBr)/1-tetradecyl-3-methylimidazolium bromide (C14mimBr), and a drug, diclofenac sodium (DFNa), in aqueous solution. The structural changes are probed by small-angle neutron scattering (SANS), dynamic light scattering (DLS), and zeta-potential measurements. SANS data and size distribution curves clearly depict the formation of low curvature structures on going from the cation-rich to anion-rich composition up to a 0.7 mole fraction of DFNa (XDFNa). The amphiphilic nature of DFNa is supposed to alter the surface charge density, which is provoked by its incorporation into resulting aggregates, as confirmed by modified zeta potential values. The modification of the average packing parameter resulting from the IL and DFNa complexation equilibrium seems to play a vital role in bringing out structural transitions of mixed aggregates. We also focused our attention to study the effect of dilution in concentrations ranging from 100 to 25 mM. At XDFNa = 0.0 and 0.1, the size of prolate ellipsoids decreases on dilution, mimicking classic behavior, but an opposite trend is observed at other XDFNa values. Dilution-induced transformation to larger aggregates is thought to be driven by the release of DFNa molecules from the mixed micelles on account of the critical micelle concentration (cmc) (solubility) mismatch between the two components. The role of other interactions such as cation-pi and pi-pi in stabilizing the mixed aggregates in addition to hydrophobic interactions is probed by (1)H NMR. PMID- 27267865 TI - Crystalline Metaphosphate Acid Salts: Synthesis in Organic Media, Structures, Hydrogen-Bonding Capability, and Implication of Superacidity. AB - Metaphosphate acids cannot be thoroughly studied in aqueous media because their acidity is leveled by the solvent, and the resulting metaphosphates are susceptible to acid-catalyzed hydrolysis. Exploration of metaphosphate acid chemistry has now been made possible with the development of a general synthetic method for organic media soluble metaphosphate acids. Protonation of the [PPN](+) salts ([PPN](+) = [N(PPh3)2](+)) of tri-, tetra-, and hexametaphosphates results in five new metaphosphate acids, [PPN]2[P3O9H] (2), [PPN]4[(P4O12)3H8] (3), [PPN]4[P6O18H2].2H2O (4), [PPN]3[P6O18H3] (5), and [PPN]2[P6O18H2(H3O)2] (6), obtained in yields of 80, 71, 66, 88, and 76%, respectively. Additionally, our synthetic method can be extended to pyrophosphate to produce [PPN][P2O7H3] (7) in 77% yield. The structural configurations of these oxoacids are dictated by strong hydrogen bonds and the anticooperative effect. Intramolecular hydrogen bonds are observed in 2, 4, and 5 and the previously reported [PPN]2[P4O12H2] (1), while intermolecular hydrogen bonds are observed in 3, 6, and 7. The hydrogen bonds in 3-7 possess short distances and are classified as low-barrier hydrogen bonds. Gas phase acidity computations reveal that the parent tri- and tetrametaphosphoric acids are superacids. Their remarkable acidity is attributable to the stabilization of their corresponding conjugate bases via intramolecular hydrogen bonding. PMID- 27267866 TI - Cs[H2NB2(C6F5)6] Featuring an Unequivocal 16-Coordinate Cation. AB - Cesium bis(perfluoro-triphenylborane)amide, Cs[H2NB2(C6F5)6] (1), has been prepared by the reaction of sodium salt and CsF in dichloromethane and water. The compound is exceptional for a [H2NB2(C6F5)6](-) salt in that it contains a monatomic solute-free cation. Determination of the molecular structure revealed a novel C2 symmetrical conformation of the weakly coordinating [H2NB2(C6F5)6](-) anion, which gives rise to an unprecedented 16-coordinate (CN 16) Cs(+) cation in a likewise unprecedented tetracosahedral arrangement of F atoms. The poor solubility of 1 allows nearly quantitative separation of Cs(+) from water, which suggests potential applications as an effective (134/137)Cs remover from nuclear waste solutions, administration as an antidote for (134/137)Cs poisoning, and use for (131/137)Cs radiotherapy (brachytherapy). Rb[H2NB2(C6F5)6].CH2Cl2 (2) has also been characterized, featuring two inequivalent Rb(+) cations having CN 10, one of which involves Rb(+)(eta(2)-Cl2CH2)2 coordination. PMID- 27267868 TI - Silver-Catalyzed Decarboxylative Alkynylation of alpha,alpha-Difluoroarylacetic Acids with Ethynylbenziodoxolone Reagents. AB - A decarboxylating alkynylation of alpha,alpha-difluoroarylacetic acids with ethynylbenziodoxolone reagents is reported. AgNO3 serves as the catalyst and K2S2O8 as the oxidant. A series of functional groups were tolerated, and moderate to good yields were obtained. PMID- 27267867 TI - Cardiovascular Disease and 10-Year Mortality in Postmenopausal Women with Clinical Features of Polycystic Ovary Syndrome. AB - BACKGROUND: Women with polycystic ovary syndrome (PCOS) have greater cardiac risk factor clustering but the link with mortality is incompletely described. OBJECTIVE: To evaluate outcomes in 295 postmenopausal women enrolled in the National Institutes of Health-National Heart, Lung, and Blood Institute (NIH NHLBI) sponsored Women's Ischemia Syndrome Evaluation (WISE) study according to clinical features of PCOS. MATERIALS AND METHODS: A total of 25/295 (8%) women had clinical features of PCOS defined by a premenopausal history of irregular menses and current biochemical evidence of hyperandrogenemia, defined as the top quartile of androstenedione (>=701 pg/mL), testosterone (>=30.9 ng/dL), or free testosterone (>=4.5 pg/mL). Cox proportional hazard model estimated death (n = 80). RESULTS: Women with clinical features of PCOS had an earlier menopause (p = 0.01), were more often smokers (p < 0.04), and trended toward more angiographic coronary artery disease (CAD) (p = 0.07) than women without these features. Cumulative 10-year mortality was 28% for women with (n = 25) versus 27% without clinical features of PCOS (n = 270) (p = 0.85). PCOS was not a significant predictor (p = NS) in prognostic models including diabetes, waist circumference, hypertension, and angiographic CAD. CONCLUSION: From this longer-term follow up of a relatively small cohort of postmenopausal women with suspected ischemia, the prevalence of PCOS is similar to the general population, and clinical features of PCOS are not associated with CAD or mortality. These findings question whether identification of clinical features of PCOS in postmenopausal women who already have known cardiovascular disease provides any additional opportunity for risk factor intervention. PMID- 27267869 TI - Effects of gremlin-2 on the transition of primordial follicles during early folliculogenesis in the human ovary. AB - OBJECTIVE: To investigate the localization and function of gremlin-2 during human ovarian folliculogenesis. STUDY DESIGN: Ovarian tissue from a gynecologic cancer patient was cultured in the presence or absence of gremlin-2 and then analyzed histologically. Growing follicles were counted by the microscopic observations of ovarian histological sections. Immunocytochemical staining was carried out to detect the expression of bone morphogenetic protein (BMP) 4 and phosphorylated Smad 1/5/8 (p-Smad 1/5/8). RESULTS: Gremlin-2 was detected in human primordial, primary, and early growing follicles before culture. By day 4 of culture, the follicle growth rate in the presence of gremlin-2 (13.7%; 24/175) was significantly lower than that of the control (54.8%; 92/175; p<0.01). BMP4 expression was similar in the presence and absence of gremlin-2, whereas the p Smad 1/5/8 signal was noticeably stronger in the absence of gremlin-2 in primordial and early-stage growing follicles. CONCLUSIONS: Gremlin-2 maintains the follicle store as primordial follicles by suppressing Smad 1/5/8 signaling in the human ovary. The data presented here provide potential insight into reproductive medicine for cases of intractable infertility, such as premature ovarian insufficiency and cancer survivors. PMID- 27267870 TI - Cross sectional, comparative study of serum erythropoietin, transferrin receptor, ferritin levels and other hematological indices in normal pregnancies and iron deficiency anemia during pregnancy. AB - OBJECTIVE: To test the correlation of the serum erythropoietin levels, serum transferrrin receptor levels and serum ferritin levels along with other hematological parameters in normal pregnant and anemic pregnant patients. STUDY DESIGN: In a prospective study, 120 pregnant women were recruited between 18 and 36 weeks of gestation; 53 normal pregnant patients, 67 anemic pregnant patients, in which, 17 had mild, 30 had moderate anemia, 20 had severe anemia. A blood sample was taken. The various hematological parameters, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), total iron binding capacity (TIBC), serum ferritin, percentage saturation of iron, serum erythropoietin (SEPO) levels, serum transferrin receptors (STfRS) were performed. For statistics, Student's 't' test, Pearson's Chi test, Mann Whitney test and Bartlett test were used as per data. RESULTS AND CONCLUSION: MCV was significantly reduced in anemic pregnancies as compared to non-anemic pregnancies (80.2+/-9.6 vs 94.12+/-9.8fl, p=0.001), MCHC was also reduced in them (30.2+/ 3.38% vs 34.2+/-2.33%, p=0.176), TIBC was significantly increased in anemic pregnancies (343.31+/-28.54% vs 322.88+/-23.84%, p=0.001), serum ferritin was significantly reduced (24.9+/-10.48MUg/L vs 31.03+/-9.98MUg/L, p=0.001), percentage saturation of iron was also reduced (53.85+/-13.21% vs 62.04+/-15.79%, p=0.0024), serum erythropoietin levels were significantly higher in anemic women (26.24+/-26.61mU/ml vs 18.12+/-19.08mU/ml, p=0.064). The levels were significantly higher in severe anemia (46.5+/-46.8mU/ml than in moderate anemia 27.4+/-28.1mU/ml and mild anemia 22.8+/-22.8mU/ml. Serum transferrin receptors were significantly higher in anemic pregnancies than in non-anemic pregnancies (1.40+/-0.0802MUg/ml vs 1.08+/-0.641MUg/ml, p=0.019) with rise being higher in severe anemia (2.28+/-0.986MUg/ml) than in moderate (1.4+/-0.816MUg/ml) and mild anemia (1.16+/-0.702MUg/ml). CONCLUSION: Various hematological parameters especially sTfR, serum erythropoietin, serum ferritin and sTfR/log ferritin levels correlate with the severity of anemia. PMID- 27267871 TI - Vitrified-warmed embryo transfer is associated with mean higher singleton birth weight compared to fresh embryo transfer. AB - OBJECTIVE: To test for differences in birth weight between singletons born after IVF with fresh embryo transfer vs. vitrified-warmed 2PN embryo transfer (vitrification protocol). DESIGN: Retrospective analysis of 464 singleton live births after IVF or ICSI during a 12 year period. SETTING: University hospital. INTERVENTIONS: Fresh embryo transfer, vitrified-warmed 2PN embryo transfer (vitrification protocol). MAIN OUTCOME MEASURES: Birth weight standardized as a z score, adjusting for gestational week at delivery and fetal sex. As a reference, birth weight means from regular deliveries from the same hospital were used. Multivariate regression analysis was used to investigate the relationship between the dependent variable z-score (fetal birth weight) and the independent predictor variables maternal age, weight, height, body mass index, RDS prophylaxis, transfer protocol, number of embryos transferred, indication for IVF treatment and sperm quality. RESULTS: The mean z-score was significantly lower after fresh transfer (-0.11+/-92) as compared to vitrification transfer (0.72+/-83) (p<0.001). Multivariate regression analysis indicated that only maternal height and maternal body mass index, but not type of cryopreservation protocol, was a significant predictor of birth weight. CONCLUSIONS: In this analysis focusing on 2PN oocytes, vitrified-warmed embryo transfer is associated with mean higher birth weight compared to fresh embryo transfer. Maternal height and body mass index are significant confounders of fetal birth weight and need to be taken into account when studying birth weight differences between ART protocols. PMID- 27267872 TI - Ultrasound guidance during hysteroscopic myomectomy in G1 and G2 Submucous Myomas: for a safer one step surgery. AB - OBJECTIVE: Hysteroscopic myomectomy is the gold standard method for treatment of submucous fibroids. Hysteroscopic myomectomy techniques for removal of submucous fibroids still have controversies. In this study we aimed to describe usefulness of ultrasound guidance in hysteroscopic myomectomy for a safe and effective removal of submucous G1 and G2 fibroids. STUDY DESIGN: This is a multicentre study. 64 symptomatic patients with submucous fibroid underwent ultrasound guided hysteroscopic myomectomy. First we excised intrauterine dome of fibroid until reaching the level of cavity wall by the method of resectoscopic (electrosurgical resection using a loop electrode) slicing. Next remnant intramural node was squeezed by uterine contractions induced. After we had excised the intrauterine dome of fibroid by slicing method, we formed cavitation for the intramural part (newly raised myoma dome). The cavity was filled with distension solution and we evaluated the margins of the uterus and the margins of the myoma by sonographically. Then the myoma was excised under ultrasonographic guidance by transabdominal probe. We obtained a regular uterine cavity. RESULTS: Mean operation time was 42+/-7min. Mean Mannitol volume was 4.3+/-1.7l and the mean intraoperational fluid deficit was 500ml. Not in any case uterine perforation was occurred. All fibroids removed totally. In 8 (19%) cases intrauterine synechiae detected and all these synechiaes were incised by a scissor during hysteroscopy. CONCLUSION: There is still no single technique proven to be unequivocally superior to the others for treating fibroids with intramural development (G1-G2). Ultrasound guided hysteroscopy seems to be an effective and safe method for resection of G1 and G2 fibroids. PMID- 27267873 TI - Rational excipient selection for co-amorphous formulations. AB - INTRODUCTION: For almost two decades there has been intense debate about whether the amorphous solid state form could resolve the solubility problems and subsequent bioavailability issues of many small molecule drugs. Since the amorphous form is a high energy and unstable state of solid matter, any material in that form requires stabilization. Areas covered: This review examines the technologies being exploited to stabilize the amorphous state in co-amorphous formulations. The review emphasizes the importance of the appropriate selection criteria of stabilizing excipient and focuses on the mechanisms of stabilization. Expert opinion: An extensive literature review has revealed that the current research seeking to achieve stabilization of an amorphous form tends to be conducted on a case-by-case basis. This kind of approach is very inefficient since it can rarely be transferred to other cases. The greatest weakness in the selection of stabilizing excipient for co-amorphous formulations is that modern computational tools have rarely been utilized as a predictive tool in the selection of the excipient. It is evident that more research needs to be done to study larger datasets with modern in silico tools, chemometrics and advanced statistical tools to achieve a more predictive, and systematic approach for the screening of stabilizing excipients to be incorporated into co-amorphous formulations. PMID- 27267874 TI - The incidence of post-traumatic stress disorder among survivors after earthquakes:a systematic review and meta-analysis. AB - BACKGROUND: Post-traumatic stress disorder (PTSD) is a common psychological disorder caused by unusual threats or catastrophic events. Little is known about the combined incidence of PTSD after earthquakes. This study aimed at evaluating the combined incidence of PTSD among survivors after earthquakes using systematic review and meta-analysis. METHODS: The electronic databases of PubMed, Embase, Web of Science and PsycARTICLES were searched for relevant articles in this study. Loney criteria were used to assess the quality of eligible articles. The combined incidence of PTSD was estimated by using the Freeman-Tukey double arcsine transformation method. Subgroup analyses were conducted using the following variables: the time of PTSD assessment, gender, educational level, marital status, damage to one's house, bereavement, injury of body and witnessing death. RESULTS: Forty-six eligible articles containing 76,101 earthquake survivors met the inclusion criteria, of which 17,706 were diagnosed as having PTSD. Using a random effects model, the combined incidence of PTSD after earthquakes was 23.66 %. Moreover, the combined incidence of PTSD among survivors who were diagnosed at not more than 9 months after earthquake was 28.76 %, while for survivors who were diagnosed at over nine months after earthquake the combined incidence was 19.48 %. A high degree of heterogeneity (I(2) = 99.5 %, p<0.001) was observed in the results, with incidence ranging from 1.20 to 82.64 %. The subgroup analyses showed that the incidence of PTSD after earthquake varied significantly across studies in relation to the time of PTSD assessment, gender, educational level, damage to one's house, bereavement, injury of body and witnessing death. However, stratified analyses could not entirely explain the heterogeneity in the results. CONCLUSIONS: Given the high heterogeneity observed in this study, future studies should aim at exploring more possible risk factors for PTSD after earthquakes, especially genetic factors. In spite of that, the results of this study suggest that nearly 1 in 4 earthquake survivors are diagnosed as having PTSD. Therefore, the local government should plan effective psychological interventions for earthquake survivors. PMID- 27267875 TI - The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study. AB - BACKGROUND: Patients with ankylosing spondylitis (AS), who by definition have radiographic sacroiliitis, typically experience symptoms for a decade or more before being diagnosed. Yet, even patients without radiographic sacroiliitis (i.e., nonradiographic axial spondyloarthritis [nr-axSpA]) report a significant disease burden. The primary objective of this study was to estimate the prevalence and clinical characteristics of nr-axSpA among patients with inflammatory back pain (IBP) in rheumatology clinics in a number of countries across the world. A secondary objective was to estimate the prevalence of IBP among patients with chronic low back pain (CLBP). METHODS: Data were collected from 51 rheumatology outpatient clinics in 19 countries in Latin America, Africa, Europe, and Asia. As consecutive patients with CLBP (N = 2517) were seen by physicians at the sites, their clinical histories were evaluated to determine whether they met the new Assessment of SpondyloArthritis international Society criteria for IBP. For those who did, their available clinical history (e.g., family history, C-reactive protein [CRP] levels) was documented in a case report form to establish whether they met criteria for nr-axSpA, AS, or other IBP. Patients diagnosed with nr-axSpA or AS completed patient-reported outcome measures to assess disease activity and functional limitations. RESULTS: A total of 2517 patients with CLBP were identified across all sites. Of these, 974 (38.70 %) fulfilled the criteria for IBP. Among IBP patients, 29.10 % met criteria for nr-axSpA, and 53.72 % met criteria for AS. The prevalence of nr-axSpA varied significantly by region (p < 0.05), with the highest prevalence reported in Asia (36.46 %) and the lowest reported in Africa (16.02 %). Patients with nr-axSpA reported mean +/- SD Ankylosing Spondylitis Disease Activity Scores based on erythrocyte sedimentation rate and CRP of 2.62 +/- 1.17 and 2.52 +/- 1.21, respectively, indicating high levels of disease activity (patients with AS reported corresponding scores of 2.97 +/- 1.13 and 2.93 +/- 1.18). Similarly, the overall Bath Ankylosing Spondylitis Disease Activity Index score of 4.03 +/- 2.23 for patients with nr-axSpA (4.56 +/- 2.17 for patients with AS) suggested suboptimal disease control. CONCLUSIONS: These results suggest that, in the centers that participated in the study, 29 % of patients with IBP met the criteria for nr-axSpA and 39 % of patients with CLBP had IBP. The disease burden in nr-axSpA is substantial and similar to that of AS, with both groups of patients experiencing inadequate disease control. These findings suggest the need for early detection of nr-axSpA and initiation of available treatment options to slow disease progression and improve patient well-being. PMID- 27267876 TI - Addressing antimicrobial resistance in China: policy implementation in a complex context. AB - The effectiveness of antibiotics in treating bacterial infections is decreasing in China because of the widespread development of resistant organisms. Although China has enacted a number of regulations to address this problem, but the impact is very limited. This paper investigates the implementation of these regulations through the lens of complex adaptive systems (CAS). It presents the findings from reviews of relevant policy documents and published papers. The paper identifies different types of agent and explores their interaction with regard to the use of antibiotics and their responses to changes of the regulations. It focuses particularly on the impact of perverse financial incentives on overall patterns of use of antibiotics. Implications for the possibilities of nonlinear results, interactive relationships, and new pathways of policy implementation are discussed. The paper concludes that policy-makers need to better understand the objectives, incentives and potential adaptive behaviors of the agents when they implement interventions to improve antibiotic use and reduce the risk of emergence of resistant organisms. PMID- 27267877 TI - Challenges encountered by local health volunteers in early diagnosis and prompt treatment of malaria in Myanmar artemisinin resistance containment zones. AB - BACKGROUND: After artemisinin resistance was reported, the Myanmar artemisinin resistance containment (MARC) project was initiated in 2011. One of the activities of MARC is to train volunteers for early diagnosis and prompt treatment by providing rapid diagnostic tests (RDT) and artemisinin combination therapy. This study aimed to fulfil the gap of information on the challenges faced by malaria volunteers in artemisinin-containment areas. METHODS: A cross sectional, descriptive study was conducted in 11 townships in MARC areas to assess the challenges in early diagnosis of malaria and treatment by malaria volunteers using qualitative and quantitative approaches. RESULTS: Altogether 405 volunteers participated in the study. Although 97.5 % of volunteers can interpret a positive result for malaria, only 41.2 % correctly stated the persistence of a positive result in recently infected cases. Over 80 % knew the effects of temperature and humidity on performance of the malaria RDT. Unexpectedly, 15.1 % perceived that expired RDTs can still be useful for diagnosis although 98.3 % of respondents cited that the overall results of RDTs were reliable. Although most of them knew the treatment for malaria based on RDT results, some could not give the correct answer, while a few (2 %) mentioned artesunate monotherapy for RDT negative cases. Training received by volunteers was also varied in study sites and 92.1 % believed that it was not sufficient. A certain portion of them faced the problem of regular supply of RDTs (9.9 %) and drugs (47.5 %), interpretation of result of RDTs (30 %), and performing blood test (20 %). The median RDT tested per month (25th, 75th percentile) was 6.0 (2.0, 15.0) indicating the need for prioritization based on endemicity. Regular reporting, supervision, monitoring system, and proper refresher training using uniform content of guideline to correct misconception of the volunteers, were needed to be strengthened. Moreover, the reliable and regular supply of materials and exchange system for expired RDTs and anti-malarials was important in the effectiveness of volunteers in MARC zones. CONCLUSIONS: Adequate refresher training, monitoring, supervision, and regular reliable supply of RDTs and anti-malarials were needed for capacity strengthening of volunteers in MARC zones. PMID- 27267878 TI - A joint effort over a period of time: factors affecting use of urate-lowering therapy for long-term treatment of gout. AB - BACKGROUND: Although international guidelines encourage urate lowering therapy (ULT) for people who have more than two attacks of gout, only 30 % of patients are prescribed it and only 40 % of those adhere to the treatment. The aim was to explore reasons for this through an exploration of patient experience and understanding of ULT treatment for gout. METHODS: A qualitative study was conducted throughout the United Kingdom. Narrative and semi-structured video recorded interviews and thematic analysis were used. RESULTS: Participants talked about their views and experiences of treatment, and the factors that affected their use of ULT. The analysis revealed five main themes: 1) knowledge and understanding of gout and its treatment; 2) resistance to taking medication; 3) uncertainty about when to start ULT; 4) experiences of using ULT; and 5) desire for information and monitoring. CONCLUSION: Patients' understanding and experiences of gout and ULT are complex and it is important for clinicians to be aware of these when working with patients. It is also important for clinicians to know that patients' perceptions and behaviour are not fixed, but can change over time, with changes to their condition, with dialogue and increased understanding. Patients want this interaction with their clinicians, through "a joint effort over a period of time". PMID- 27267880 TI - Evaluation of rotigotine transdermal patch for the treatment of apathy and motor symptoms in Parkinson's disease. AB - BACKGROUND: This multicenter, double-blind, placebo-controlled study assessed the efficacy of rotigotine transdermal patch on apathy and motor symptoms in patients with Parkinson's disease (PD). METHODS: Patients with PD-associated apathy (Unified Parkinson's Disease Rating Scale [UPDRS] I item 4 [motivation] >=2 and patient-rated Apathy Scale [AS] >=14) were randomized 1:1:1 to "low-dose" rotigotine (<=6 mg/24 h for early PD [those not receiving levodopa] or <=8 mg/24 h for advanced PD [those receiving levodopa]), "high-dose" rotigotine (<=8 mg/24 h for early PD or <=16 mg/24 h for advanced PD), or placebo, and maintained at optimal/maximal dose for 12 weeks. Coprimary efficacy variables were: change from baseline to End of Maintenance in patient-rated AS and UPDRS II + III total score. Recruitment was stopped after an interim futility analysis; therefore, all p values are exploratory. RESULTS: Of 122 patients randomized, 81.1 % completed the study (placebo, n = 32/40 [80.0 %]; low-dose rotigotine, n = 30/41 [73.2 %]; high-dose rotigotine, n = 37/41 [90.2 %]). No treatment difference was observed in the change in patient-rated AS (least squares mean [95 % confidence interval (CI)] difference: low-dose, 0.04 [-2.42, 2.50], p =0.977; high-dose, -0.22 [ 2.61, 2.18], p = 0.859). Rotigotine improved UPDRS II + III total scores versus placebo (least squares mean [95 % CI] treatment difference: low-dose, -7.29 [ 12.30, -2.28], p = 0.005; high-dose, -6.06 [-10.90, -1.21], p = 0.015), and the "mood/apathy" domain of the Non-Motor Symptom Scale as rated by the investigator (secondary outcome). The most frequent adverse events in rotigotine-treated patients were application site reactions, somnolence, and nausea. CONCLUSIONS: Rotigotine did not improve PD-associated apathy as rated by the patient but provided clinically relevant improvement in motor control and activities of daily living. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01782222 . Trial registration date: January 30, 2013. PMID- 27267882 TI - Relationship Status and Long-Term Care Facility Use in Later Life. PMID- 27267879 TI - Amyloid Precursor-Like Protein 2 deletion-induced retinal synaptopathy related to congenital stationary night blindness: structural, functional and molecular characteristics. AB - BACKGROUND: Amyloid precursor protein knockout mice (APP-KO) have impaired differentiation of amacrine and horizontal cells. APP is part of a gene family and its paralogue amyloid precursor-like protein 2 (APLP2) has both shared as well as distinct expression patterns to APP, including in the retina. Given the impact of APP in the retina we investigated how APLP2 expression affected the retina using APLP2 knockout mice (APLP2-KO). RESULTS: Using histology, morphometric analysis with noninvasive imaging technique and electron microscopy, we showed that APLP2-KO retina displayed abnormal formation of the outer synaptic layer, accompanied with greatly impaired photoreceptor ribbon synapses in adults. Moreover, APLP2-KO displayed a significant decease in ON-bipolar, rod bipolar and type 2 OFF-cone bipolar cells (36, 21 and 63 %, respectively). Reduction of the number of bipolar cells was accompanied with disrupted dendrites, reduced expression of metabotropic glutamate receptor 6 at the dendritic tips and alteration of axon terminals in the OFF laminae of the inner plexiform layer. In contrast, the APP-KO photoreceptor ribbon synapses and bipolar cells were intact. The APLP2-KO retina displayed numerous phenotypic similarities with the congenital stationary night blindness, a non-progressive retinal degeneration disease characterized by the loss of night vision. The pathological phenotypes in the APLP2-KO mouse correlated to altered transcription of genes involved in pre- and postsynatic structure/function, including CACNA1F, GRM6, TRMP1 and Galpha0, and a normal scotopic a-wave electroretinogram amplitude, markedly reduced scotopic electroretinogram b-wave and modestly reduced photopic cone response. This confirmed the impaired function of the photoreceptor ribbon synapses and retinal bipolar cells, as is also observed in congenital stationary night blindness. Since congenital stationary night blindness present at birth, we extended our analysis to retinal differentiation and showed impaired differentiation of different bipolar cell subtypes and an altered temporal sequence of development from OFF to ON laminae in the inner plexiform layer. This was associated with the altered expression patterns of bipolar cell generation and differentiation factors, including MATH3, CHX10, VSX1 and OTX2. CONCLUSIONS: These findings demonstrate that APLP2 couples retina development and synaptic genes and present the first evidence that APLP2 expression may be linked to synaptic disease. PMID- 27267881 TI - Factors contributing to chronic ankle instability: a protocol for a systematic review of systematic reviews. AB - BACKGROUND: Ankle sprains are a significant clinical problem. Researchers have identified a multitude of factors contributing to the presence of recurrent ankle sprains including deficits in balance, postural control, kinematics, muscle activity, strength, range of motion, ligament laxity and bone/joint characteristics. Unfortunately, the literature examining the presence of these factors in chronic ankle instability (CAI) is conflicting. As a result, researchers have attempted to integrate this evidence using systematic reviews to reach conclusions; however, readers are now faced with an increasing number of systematic review findings that are also conflicting. The overall aim of this review is to critically appraise the methodological quality of previous systematic reviews and pool this evidence to identify contributing factors to CAI. METHODS: A systematic review will be conducted on systematic reviews that investigate the presence of various deficits identified in CAI. Databases will be searched using pre-determined search terms. Reviews will then be assessed for inclusion based on the set eligibility criteria. Two independent reviewers will assess the articles for inclusion before evaluating the methodological quality and presence of bias of the included studies; any disagreements will be resolved by discussion between reviewers to reach consensus or by a third reviewer. Data concerning the specific research question, search strategy, inclusion/exclusion criteria, population, method and outcomes will be extracted. Findings will be analysed with respect to the methodological quality of the included reviews. DISCUSSION: It is expected that this review will clarify the cause of contradicting findings in the literature and facilitate future research directions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016032592 . PMID- 27267883 TI - Four members of obesity forum resign over controversial diet report. PMID- 27267884 TI - Genetic diversity of species Fowl aviadenovirus D and Fowl aviadenovirus E. AB - Complete genomes of eight reference strains representing different serotypes within the species Fowl aviadenovirus D (FAdV-D) and Fowl aviadenovirus E (FAdV E) were sequenced. The sequenced genomes of FAdV-D and FAdV-E members comprise 43 287 to 44 336 bp, and have a gene organization identical to that of an earlier sequenced FAdV-D member (strain A-2A). Highest diversity was noticed in the hexon and fiber genes and ORF19. All genomes sequenced in this study contain one fiber gene. Phylogenetic analyses and G+C content support the division of the genus Aviadenovirus into the currently recognized species. Our data also suggest that strain SR48 should be considered as FAdV-11 instead of FAdV-2 and similarly strain HG as FAdV-8b. The present results complete the list of genome sequences of reference strains representing all serotypes in species FAdV-D and FAdV-E. PMID- 27267885 TI - Longitudinal measurement invariance in prospective oral health-related quality of life assessment. AB - BACKGROUND: Prospective assessments of oral health-related quality of life (OHRQoL) changes are prone to response shift effects when patients reconceptualize, reprioritize, or recalibrate the perceived meanings of OHRQoL test items. If this occurs, OHRQoL measurements are not "invariant" and may reflect changes in problem profiles or perceptions of OHRQoL test items. This suggests that response shift effects must be measured and controlled to achieve valid prospective OHRQoL measurement. The aim of this study was to quantify response shift effects of Oral Health Impact Profile (OHIP) scores in prospective studies of prosthodontic patients. METHODS: Data came from the Dimensions of Oral Health-Related Quality of Life Project. The final sample included 554 patients who completed the OHIP questionnaire on two occasions: pre- and post-treatment. Only items that compose the 14-item OHIP were analyzed. Structural equation models that included pre- and post-treatment latent factors of OHRQoL with different across-occasion constraints for factor loadings, intercepts, and residual variances were fit to the data using confirmatory factor analysis. RESULTS: Data fit both the unconstrained model (RMSEA = .038, SRMR = .051, CFI = .92, TLI = .91) and the partially constrained model with freed residual variances (RMSEA = .037, SRMR = .064, CFI = .92, TLI = .92) well, meaning that the data are well approximated by a one-factor model at each occasion, and suggesting strong factorial across-occasion measurement invariance. CONCLUSIONS: The results provided cogent evidence for the absence of response shift in single factor OHIP models, indicating that longitudinal OHIP assessments of OHRQoL measure similar constructs across occasions. PMID- 27267886 TI - Re: Jennifer R. Rider, Kathryn M. Wilson, Jennifer A. Sinnott, Rachel S. Kelly, Lorelei A. Muccia, Edward L. Giovannucci. Ejaculation Frequency and Risk of Prostate Cancer: Updated Results with an Additional Decade of Follow-up. Eur Urol 2016;70:974-82. PMID- 27267888 TI - Retraction. PMID- 27267887 TI - Strategies in primary healthcare to implement early identification of risky alcohol consumption: why do they work or not? A qualitative evaluation of the ODHIN study. AB - BACKGROUND: Screening and brief interventions (SBI) in primary healthcare are cost-effective in risky drinkers, yet they are not offered to all eligible patients. This qualitative study aimed to provide more insight into the factors and mechanisms of why, how, for whom and under what circumstances implementation strategies work or do not work in increasing SBI. METHODS: Semi-structured interviews were conducted between February and July 2014 with 40 GPs and 28 nurses in Catalonia, the Netherlands, Poland, and Sweden. Participants were purposefully selected from the European Optimising Delivery of Healthcare Interventions (ODHIN) trial. This randomised controlled trial evaluated the influence of training and support, financial reimbursement and an internet-based method of delivering advice on SBI. Amongst them were 38 providers with a high screening performance and 30 with a low screening performance from different allocation groups. Realist evaluation was combined with the Tailored Implementation for Chronic Diseases framework for identification of implementation determinants to guide the interviews and analysis. Transcripts were analysed thematically with the diagram affinity method. RESULTS: Training and support motivated SBI by improved knowledge, skills and prioritisation. Continuous provision, sufficient time to learn intervention techniques and to tailor to individual experienced barriers, seemed important T&S conditions. Catalan and Polish professionals perceived financial reimbursement to be an additional stimulating factor as well, as effects on SBI were smoothened by personnel levels and salary levels. Structural payment for preventive services rather than a temporary project based payment, might have increased the effects of financial reimbursement. Implementing e-BI seem to require more guidance than was delivered in ODHIN. Despite the allocation, important preconditions for SBI routine seemed frequent exposure of this topic in media and guidelines, SBI facilitating information systems, and having SBI in protocol-led care. Hence, the second order analysis revealed that the applied implementation strategies have high potential on the micro professional level and meso-organisational level, however due to influences from the macro- level such as societal and political culture the effects risks to get nullified. CONCLUSIONS: Essential determinants perceived for the implementation of SBI routines were identified, in particular for training and support and financial reimbursement. However, focusing only on the primary healthcare setting seems insufficient and a more integrated SBI culture, together with meso- and macro-focused implementation process is requested. TRIAL REGISTRATION: ClinicalTrials.gov. Trial identifier: NCT01501552 . PMID- 27267889 TI - Post-discharge stroke patients' information needs as input to proposing patient centred eHealth services. AB - BACKGROUND: Despite the potential of eHealth services to revolutionize the way healthcare and prevention is provided many applications developed for patients fail to deliver their promise. Therefore, the aim of this study is to use patient journey mapping to explore post-discharge stroke patients' information needs to propose eHealth services that meet their needs throughout their care and rehabilitation processes. METHODS: Three focus groups with younger (<65 years) and older (> = 65 years) stroke patients were performed. Content analysis was used to analyse the data. Stroke patients' information needs was explored using patient journey model. RESULTS: Four main events (discharge from hospital, discharge from rehab clinic, coming home, and clinical encounters) and two phases (at rehab clinic, at home) have been identified in patients' post-discharge journey. The main categories identified in this study indicate that patients not only need to have access to health related information about their care and rehabilitation processes but also practical guidance through healthcare and community services. Patients also have different information needs at different events and during different phases. Potential supportive eHealth services were suggested by the researchers considering different parts of the patients' journeys. CONCLUSIONS: Patient journey models and qualitative analysis of patients' information needs are powerful tools that can be used to improve healthcare from a patient perspective. As patients' understanding of their illness changes over time, their need of more flexible support throughout the care and rehabilitation processes increases. To design appropriate eHealth services that meet patients' information needs, it is imperative to understand the current care and rehabilitation processes and identify patients' information needs throughout their journey. PMID- 27267890 TI - What role can gender-transformative programming for men play in increasing men's HIV testing and engagement in HIV care and treatment in South Africa? AB - Men are less likely than women to test for HIV and engage in HIV care and treatment. We conducted in-depth interviews with men participating in One Man Can (OMC) - a rights-based gender equality and health programme intervention conducted in rural Limpopo and Eastern Cape, South Africa - to explore masculinity-related barriers to HIV testing/care/treatment and how participation in OMC impacted on these. Men who participated in OMC reported an increased capability to overcome masculinity-related barriers to testing/care/treatment. They also reported increased ability to express vulnerability and discuss HIV openly with others, which led to greater willingness to be tested for HIV and receive HIV care and treatment for those who were living with HIV. Interventions that challenge masculine norms and promote gender equality (i.e. gender transformative interventions) represent a promising new approach to address men's barriers to testing, care and treatment. PMID- 27267891 TI - Effects of Black Raspberry Extract and Protocatechuic Acid on Carcinogen-DNA Adducts and Mutagenesis, and Oxidative Stress in Rat and Human Oral Cells. AB - Effects of black raspberry (BRB) extract and protocatechuic acid (PCA) on DNA adduct formation and mutagenesis induced by metabolites of dibenzo[a,l]pyrene (DBP) were investigated in rat oral fibroblasts. The DBP metabolites, (+/-)-anti 11,12-dihydroxy-11,12,-dihydrodibenzo[a,l]pyrene (DBP-diol) and 11,12-dihydroxy 13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DBPDE) induced dose dependent DNA adducts and mutations. DBPDE was considerably more potent, whereas the parent compound had no significant effect. Treatment with BRB extract (BRBE) and PCA resulted in reduced DBP-derived DNA adduct levels and reduced mutagenesis induced by DBP-diol, but only BRBE was similarly effective against (DBPDE). BRBE did not directly inactivate DBPDE, but rather induced a cellular response enhanced DNA repair. When BRBE was added to cells 1 day after the DBP-diol, the BRBE greatly enhanced removal of DBP-derived DNA adducts. As oxidative stress can contribute to several stages of carcinogenesis, BRBE and PCA were investigated for their abilities to reduce oxidative stress in a human leukoplakia cell line by monitoring the redox indicator, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF) in cellular and acellular systems. BRBE effectively inhibited the oxidation, but PCA was only minimally effective against H2DCF. These results taken together provide evidence that BRBE and PCA can inhibit initiation of carcinogenesis by polycyclic aromatic hydrocarbons; and in addition, BRBE reduces oxidative stress. Cancer Prev Res; 9(8); 704-12. (c)2016 AACR. PMID- 27267893 TI - A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia. AB - Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-kappaB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2 96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. (c)2016 AACR. PMID- 27267894 TI - Life-saving first aid tips in the palm of your hands...courtesy of the Red Cross. PMID- 27267892 TI - STAT3 as a Chemoprevention Target in Carcinogen-Induced Head and Neck Squamous Cell Carcinoma. AB - Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal disease due, in large part, to a high rate of second primary tumor (SPT) formation. The 4 nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis provides a robust system in which to study chemopreventive agents in the context of chemically induced HNSCC tumors. STAT3 is a potent oncogene that is hyperactivated by tyrosine phosphorylation early in HNSCC carcinogenesis and is a rational therapeutic target. We recently reported that loss-of-function of the STAT3 phosphatase PTPRT promotes STAT3 activation in HNSCC tumors and preclinical models and may serve as a predictive biomarker of response to STAT3 inhibitors, including the small-molecule Stattic. We therefore investigated the hypothesis that Ptprt-knockout (KO) mice would be more susceptible to 4-NQO-induced oral carcinogenesis and more sensitive to Stattic-mediated chemoprevention compared with wild-type (WT) mice. Herein, we demonstrate that Ptprt WT and KO mice develop similar spectra of HNSCC disease severity upon 12 weeks of 4-NQO administration, with no apparent effect of Ptprt genotype on carcinogenesis or treatment outcome. Targeting of STAT3 with Stattic resulted in a chemopreventive effect against 4-NQO-induced oral cancer (P = 0.0402). While these results do not support a central role for PTPRT in 4-NQO-induced HNSCC carcinogenesis, further investigation of STAT3 as a chemoprevention target in this cancer is warranted. Cancer Prev Res; 9(8); 657-63. (c)2016 AACR. PMID- 27267895 TI - Sport, exercise and the menstrual cycle: where is the research? PMID- 27267896 TI - The isotype repertoire of antibodies against novel UH-RA peptides in rheumatoid arthritis. AB - BACKGROUND: Recently, autoantibodies against novel UH-RA peptides (UH-RA.1 and UH RA.21) were identified as candidate biomarkers for patients with rheumatoid arthritis (RA) who are seronegative for the current diagnostic markers rheumatoid factor and anticitrullinated protein antibodies. Previously, screening for anti UH-RA autoantibodies was based on measuring the immunoglobulin (Ig) G response. We aimed to investigate whether measurement of other isotypes could improve the performance of diagnostic testing. In addition, assigning the isotype profile might provide valuable information on effector functions of the antibodies. METHODS: The isotype profile of antibodies against UH-RA.1 and UH-RA.21 was studied. The IgG, IgM, and IgA classes, together with the 4 different IgG subclasses, were determined in 285 patients with RA, 88 rheumatic control subjects, and 90 healthy control subjects. RESULTS: Anti-UH-RA.1 antibodies were primarily of the IgM isotype and twice as prevalent as IgG (IgG3-dominated) and IgA. RA sensitivity when testing for anti-UH-RA.1 IgM was shown to be higher than when testing for the IgG isotype: 18 % versus 9 % sensitivity when RA specificity was set to 90 %. Within antibodies against UH-RA.21, IgG and IgA were more common than IgM. Different anti-UH-RA.21 IgG subclasses were found, with the highest prevalence found for IgG2. Combined testing for IgG and IgA slightly increased RA sensitivity of UH-RA.21-specific antibody testing to 27 % compared with solely testing for IgG (23 %). Notably, a higher number of anti-UH-RA.21 antibody isotypes was related to increased levels of erythrocyte sedimentation rate. Finally, for both antibody responses, the full antibody isotype use was demonstrated in early and seronegative disease. CONCLUSIONS: The isotype distribution of anti-UH-RA.1 and anti-UH-RA.21 antibodies was successfully outlined, and, for antibodies against UH-RA.1, we found that isotype-specific testing might have implications for diagnostic testing. The exact mechanisms by which the different antibody isotypes act still have to be unraveled. PMID- 27267897 TI - The relationship between self-reported mental health and redeemed prescriptions of antidepressants: a register-based cohort study. AB - BACKGROUND: Poor mental health is a major problem in most western societies, especially predominant among young adults. However, associations of self-reported poor mental health with subsequent psychiatric or medical treatment are unknown. We examined the relation between self-reported mental health and redeeming prescriptions of antidepressants among three age groups. METHODS: We analyzed data from 16,233 individuals aged 16 years and over randomly selected to participate in the 2010 North Denmark Region Health Survey completed in February 2010. Mental health was defined according to the Short-Form 12 instrument (SF-12) and dichotomized into poor and good. Outcome data were retrieved from administrative information on redeemed prescriptions of antidepressants between February 2010 and December 2012. Crude cumulative incidence curves were produced to illustrate the probability of redeeming new prescriptions of antidepressants over time. Cox regression analysis was used to estimate risk of redeeming prescriptions of antidepressants when having poor mental health, adjusted for preselected explanatory covariates. RESULTS: Among the young (16-29 years-old), 620 (23 %) participants suffered from poor mental health. Among the adults (30-59 years-old) and elderly (60 years-old or over), 1592 (18 %) participants and 723 (15 %) reported poor mental health, respectively. Overall, women were more likely than men to rate their mental health as poor. For all age groups, there was an increased probability for redeeming prescriptions of antidepressants when having poor mental health. The hazard ratio [HR] for redeeming prescriptions of antidepressants for those reporting poor versus good mental health, adjusted for sex, ethnicity, marital status, education level, occupational status, smoking and physical activity was 3.1 (95 % confidence interval [CI] 2.20-4.29) for young participants. For adults, the HR was 2.3 (95 % CI 1.86-2.78) and for elderly, it was 3.5 (95 % CI 2.66-4.57). CONCLUSION: Self-reported poor mental health was more frequent among younger than older participants. Overall, antidepressants were the most often used treatment. An increased probability of redeeming antidepressant prescriptions when having self-reported poor mental health was observed in all age groups. These findings suggest that frequent reporting of poor mental health is a common issue for all age groups that needs more attention. PMID- 27267898 TI - Addressing the impact of economic sanctions on Iranian drug shortages in the joint comprehensive plan of action: promoting access to medicines and health diplomacy. AB - BACKGROUND: The U.S Congress initiated sanctions against Iran after the 1979 U.S. Embassy hostage crisis in Tehran, and since then the scope of multilateral sanctions imposed by the United States, the European Union, and the United Nations Security Council have progressively expanded throughout the intervening years. Though primarily targeted at Iran's nuclear proliferation activities, sanctions have nevertheless resulted in negative public health outcomes for ordinary Iranian citizens. This includes creating vital domestic shortages to life-saving medicines, leaving an estimated 6 million Iranian patients with limited treatment access for a host of diseases. Sanctions have also crippled Iran's domestic pharmaceutical industry, leading to the disruption of generic medicines production and forcing the country to import medicines and raw materials that are of lower or questionable quality. DISCUSSION: Countries such as the United States have responded to this medical crisis by implementing export control exemptions with the aim of easing the trade of humanitarian goods (including certain pharmaceuticals and medical devices). However, despite these efforts, pharmaceutical firms and international banking institutions remain cautious about doing business with Iran, leaving the country faced with continuing shortages. We conducted a review of key characteristics of the Iranian drug shortage that identified 73 shortage drugs that closely tracked with the disease burden in the country. Additionally, 44 % of these drugs were also classified as essential medicines by the World Health Organization. A vast majority of these drugs were also covered under export control exemptions that theoretically should make them easier to procure, but nevertheless will still in shortage. Based on our review of the sanctions regulatory framework and key characteristics of the Iranian drug shortage, we propose policy intervention leveraging the recently negotiated P5 + 1 agreement that begins the process of providing Iran relief from the international economic sanctions regime. This specifically includes advocating for the application of "health diplomacy" in ongoing multilateral negotiations following commencement of "implementation day," by advocating for an additional set of reform measures incorporated into this historic negotiation that will finally address the humanitarian and medical crisis of drug shortages in Iran. PMID- 27267899 TI - A case report of a giant rectal adenoma causing secretory diarrhea and acute renal failure: McKittrick-Wheelock syndrome. AB - BACKGROUND: The McKittrick-Wheelock syndrome is a rare depletion syndrome caused by a secretory villous adenoma or a carcinoma of the rectosigmoid tract. An aggressive hydroelectrolyte rebalancing is often needed, and curative treatment is obtained only with complete removal of the lesion, by endoscopy or surgery. Low clinical suspicion often delays the diagnosis, resulting in detrimental complications. CASE PRESENTATION: We report the case of a 75-year-old woman, presenting to the emergency department with acute renal failure and electrolyte imbalance, reporting an history of recurrent episodes of dehydration and chronic diarrhea. After being admitted to the nephrology department she underwent diagnostic investigation that revealed the presence of a giant adenoma of the rectum. The patients received supportive therapy and was subsequently treated with surgery, with a favorable outcome. CONCLUSIONS: A prompt diagnosis plays an important role in the treatment of McKittrick-Wheelock syndrome. We describe a case of this condition in detail and review the related literature, underlining the typical diagnostic features and exploring the possible therapeutic options. PMID- 27267900 TI - Postpartum depressive symptoms and its association to daytime sleepiness and restless legs during pregnancy. AB - BACKGROUND: Postpartum depression is a common condition, which consequences might be harmful for both mother and child. Since sleep and depression are closely related it is possible that women who suffer from sleep related problems during pregnancy are more likely to develop depression in the postpartum period. This study aims to investigate the possible association between depressive symptoms in the postpartum period and sleep related problems during pregnancy. METHODS: In this study 293 women in the last trimester of pregnancy answered a questionnaire about symptoms of restless legs, snoring and daytime sleepiness. They also completed the Epworth Sleepiness Scale (ESS). The same women were screened for depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) four to ten weeks after giving birth. Additional information about social data, pregnancy and delivery was received from the medical charts. RESULTS: Women with postpartum depressive symptoms had higher prevalence of excessive daytime sleepiness defined as ESS score >=10 (OR 3.84, CI 1.57-9.39), and restless legs syndrome (OR 2.837 CI 1.18-6.84) in last trimester of pregnancy, when adjusted for socio-demographic factors and obstetric risk factors. No association was found between postpartum depressive symptoms and snoring. CONCLUSIONS: Depressive symptoms after childbirth are preceded by sleep related problems such as daytime sleepiness and restless legs, already during pregnancy. The results from Epworth Sleepiness Scale and a questionnaire concerning Restless Legs Syndrome completed during pregnancy might be a valuable contribution for detecting women at risk for postpartum depression, enabling preventive interventions. PMID- 27267901 TI - Effectiveness and content analysis of interventions to enhance medication adherence in hypertension: a systematic review and meta-analysis protocol. AB - BACKGROUND: Hypertension control through pharmacological treatment has led to substantial benefits in the prevention of morbidity and mortality from cardiovascular diseases. However, evidence from a number of studies suggests that as many as 50 to 80 % of patients treated for hypertension have low adherence to their treatment regimen. The objective of this systematic review is to evaluate the effectiveness of medication adherence interventions for hypertension. In addition, we aim to explore what barriers and facilitators in the interventions may have been targeted and how these might be related to the effect size on blood pressure (BP). METHODS: This review is a hypertension-specific update to the previous Cochrane Review by Nieuwlaat et al. (2014) on interventions to enhance medication adherence. A systematic literature search will be carried out, and two authors will independently screen titles and abstracts for their eligibility for inclusion and independently extract data from the selected studies and assess the methodological quality using the Cochrane Collaboration Risk of Bias Tool. A meta analysis will be conducted, and additionally, theoretical factors in interventions will be identified using the Theoretical Domains Framework. DISCUSSION: This review will generate new information by quantitatively evaluating the effectiveness of adherence interventions for hypertension and potentially identify which theoretical domains are associated with more effective interventions and which domains have not been the subject of intervention development. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033358. PMID- 27267903 TI - Increased uptake and improved outcomes of bowel cancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England. AB - BACKGROUND: The National Health Service Bowel Cancer Screening Programme (BCSP) in England uses a guaiac-based faecal occult blood test (gFOBt). A quantitative faecal immunochemical test (FIT) for haemoglobin (Hb) has many advantages, including being specific for human blood, detecting Hb at a much lower concentration with a single faecal sample and improved uptake. METHODS: In 2014, a large comparative pilot study was performed within BCSP to establish the acceptability and diagnostic performance of FIT. Over a 6-month period, 40 930 (1 in 28) subjects were sent a FIT (OC-SENSOR) instead of a gFOBt. A bespoke FIT package was used to mail FIT sampling devices to and from FIT subjects. All participants positive with either gFOBt or FIT (cut-off 20 ug Hb/g faeces) were referred for follow-up. Subgroup analysis included cut-off concentrations, age, sex, screening history and deprivation quintile. RESULTS: While overall uptake increased by over 7 percentage points with FIT (66.4% vs 59.3%, OR 1.35, 95% CI 1.33 to 1.38), uptake by previous non-responders almost doubled (FIT 23.9% vs gFOBt 12.5%, OR 2.20, 95% CI 2.10 to 2.29). The increase in overall uptake was significantly higher in men than women and was observed across all deprivation quintiles. With the conventional 20 ug/g cut-off, FIT positivity was 7.8% and ranged from 5.7% in 59-64-year-old women to 11.1% in 70-75-year-old men. Cancer detection increased twofold and that for advanced adenomas nearly fivefold. Detection rates remained higher with FIT for advanced adenomas, even at 180 ug Hb/g. CONCLUSIONS: Markedly improved participation rates were achieved in a mature gFOBt-based national screening programme and disparities between men and women were reduced. High positivity rates, particularly in men and previous non respondents, challenge the available colonoscopy resource, but improvements in neoplasia detection are still achievable within this limited resource. PMID- 27267902 TI - Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR 200a. AB - BACKGROUND: Glioma is one of the most common and aggressive primary malignant tumor in the brain. Accumulating evidences indicated that aberrantly expressed non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), contribute to tumorigenesis. However, potential mechanisms between lncRNAs and miRNAs in glioma remain largely unknown. METHODS: Long non-coding RNA activated by TGF-beta (LncRNA-ATB) expression in glioma tissues and cells was quantified by quantitative reverse transcription-PCR. Glioma cell lines U251 and A172 were transfected with sh-ATB, miR-200a mimics, miR-200a inhibitors, after we assayed the cell phenotype and expression of the relevant molecules. Dual luciferase reporter assay, RIP and a xenograft mouse model were used to examine the expression of sh-ATB and its target gene miR-200a. RESULTS: ATB is abnormally up-regulated both in glioma tissues and cell lines compared with normal brain tissues, and glioma patients with high ATB expression had shorter overall survival time. Knockdown of ATB significantly inhibits glioma malignancy, including cell proliferation, colony formation, migration, invasion in vitro, and the xenograft tumor formation in vivo. In addition, ATB was confirmed to target miR-200a, and miR-200a inhibition reversed the malignant characteristics of ATB knockdown on glioma cells. In particular, ATB may act as a ceRNA, effectively becoming a sink for miR-200a, thereby modulating the derepression of TGF-beta2. CONCLUSIONS: Our findings suggest that ATB plays an oncogenic role of glioma cells by inhibiting miR-200a and facilitating TGF-beta2 in glioma, thereby may represent a potential therapeutic target for the treatment of human glioma. PMID- 27267904 TI - Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced autophagy of mouse Leydig TM3 cells in vitro. AB - BACKGROUND: As a plasticizer, plastic softener, and flame-retardant, tri-ortho cresyl phosphate (TOCP) is and has been widely used in industry and reported to have a toxic effect on the male reproductive system in animals besides neurotoxicity and immunotoxicity. We have reported that TOCP inhibits spermatogenesis and induces autophagy of rat spermatogonial stem cells, but it is still unknown whether TOCP induces autophagy of mouse Leydig cells and its potential mechanism. METHODS: Cell viability was observed by MTT assay. Level of testosterone was measured by radioimmunoassay. Apoptosis was observed by AnnexinV FITC/PI assay. The contents of LC3, Atg5-Atg12, and Beclin 1 were detected by Western blotting analysis. Autophagosomes were investigated by transmission electron microscopy. The contents of MDA and GSH and the activities of SOD, GSH PX, total antioxidant status (TAS) and total oxidant status (TOS) were measured by oxidative stress kits. RESULTS: The present study shows that TOCP markedly inhibited viability and testosterone output of mouse Leydig TM3 cells but had no effect on apoptosis. However, TOCP significantly increased both LC3-II and the ratio of LC3-II to LC3-I and the contents of autophagy proteins Atg5 and Beclin 1. Transmission electron microscopy (TEM) showed that TOCP increased autophagic vacuoles of the cytoplasm, indicating that TOCP could induce autophagy of the cells. TOCP significantly induced oxidative stress of mouse Leydig TM3 cells. H2O2 also inhibited viability and induced autophagy of the cells; however, inhibition of oxidative stress by N-acetyl-L-cysteine (NAC) could rescue the inhibition of cell viability and induction of autophagy by TOCP. CONCLUSIONS: The results show oxidative stress might be involved in TOCP-induced autophagy of mouse Leydig TM3 cells. PMID- 27267905 TI - Association between multimorbidity patterns and chronic pain in elderly primary care patients: a cross-sectional observational study. AB - BACKGROUND: Multimorbidity is a highly prevalent health problem, which may reduce adherence, produce conflicts in treatment, and is not yet supported by evidence based clinical recommendations. Many older people suffer from more than one chronic disease as well as from chronic pain. There is some evidence that disease management can become more complex if multimorbid patients suffer from chronic pain. In order to better consider the patients' comorbidity spectrum in clinical pain treatment recommendations, evidence is needed regarding which disease combinations are frequently related with the presence of chronic pain. Therefore, our aim is to identify diseases and disease combinations in a multimorbid population, which are associated with the patient-reported presence of chronic pain. METHODS: Analyses are based on cross-sectional data of the MultiCare Cohort Study, an observational cohort study based on interviews with 3189 multimorbid patients aged 65+, randomly selected from 158 practices, and their GPs. The response rate was 46.2 %. Data were collected in GP interviews and comprehensive patient interviews. Diseases and disease combinations associated with chronic pain were identified by CART (classification and regression tree) analyses performed separately for both genders. 46 chronic conditions were used as predictor variables and a dichotomized score from the Graded Chronic Pain Scale was used as outcome variable. RESULTS: About 60 % of the study participants were female. Women more often reported chronic pain than men. The most important predictor of a higher pain level in the female population was chronic low back problems, especially if combined with chronic gastritis, hyperuricemia/gout, cardiac insufficiency, neuropathies or depression. Regarding the pain level the male population was also divided best by chronic low back problems, especially if combined with intestinal diverticulosis, neuropathies or chronic ischemic heart disease. CONCLUSIONS: Our analyses are a first step in identifying diseases and disease combinations that are related to chronic pain. The most important condition seems to be low back problems. Back pain and pain in other body regions seems to be interrelated with cardiometabolic conditions. In women, psychosocial issues like depression also seem to be relevant. TRIAL REGISTRATION: ISRCTN89818205 . PMID- 27267907 TI - Alcohol Use after Liver Transplantation is Independent of Liver Disease Etiology. AB - AIM: To assess alcohol use after liver transplantation (LT) and compare liver transplant recipients for alcoholic liver disease (ALD) with recipients for non ALD causes. METHODS: National Institute of Diabetes and Digestive and Kidney Diseases liver transplant database stratified to ALD and non-ALD causes. RESULTS: Among 488 LT recipients reporting pre-transplant alcohol use (147 ALD), proportion of LT recipients reporting alcohol use was similar comparing ALD and non-ALD transplants (25.4% vs. 27.2%; P = 0.56). Among ALD transplants, of 31 with alcohol use, 23 (74%) relapsed at >=2 year, 25 (80%) reported intermittent drinking and 4 (13%) reported heavy drinking. Among Non-ALD recipients, alcohol use was equally distributed to within 2, 2-5 and after 5 years of LT with 82% reporting intermittent drinking and 9% heavy drinking. Patients with pre transplant drinking of >20 years and abstinence duration of <2 years were over 2.5-fold likely to report post-transplant alcohol use compared to drinking of >20 years and abstinence of >2 years, 2.56 [95% CI: 1.41-4.67]. Etiology (ALD vs. non ALD) did not predict post-transplant alcohol use. Of 139 ALD patients with follow up biopsy data, 13 (7 with post-transplant alcohol use) had steatohepatitis. Histology on 319 non-ALD recipients showed recurrent disease in 91, none due to alcohol. Overall survival was similar between drinkers and abstainers (71% vs. 66%; P = 0.35). Recurrent ALD was cause of death in one ALD and none of non-ALD patients. CONCLUSION: Alcohol use after LT is independent of LT indication. Patients with non-ALD etiology should be carefully screened for alcohol use prior to LT to identify those at risk for post-LT alcohol use. PMID- 27267908 TI - Silver-Free Palladium-Catalyzed sp(3) and sp(2) C-H Alkynylation Promoted by a 1,2,3-Triazole Amine Directing Group. AB - Triazole amine was identified as an effective directing group in promoting C-H alkynylation under silver-free conditions. No other external oxidant was required, and the alkynylation products were received in good to excellent yields. X-ray crystallographic analysis confirmed a direct C-H activation intermediate. Other typical directing groups, including pyridine amine (PIP) and 8-aminoquinoline (QA), gave almost no reaction under identical conditions, which highlighted the unique reactivity of the triazole directing group in direct C-H functionalization. PMID- 27267909 TI - Surface Mobility of Amorphous o-Terphenyl: A Strong Inhibitory Effect of Low Concentration Polystyrene. AB - Previous work has shown that a surface wave on amorphous o-terphenyl (OTP) decays by viscous flow at high temperatures and by surface diffusion at low temperatures. We report that the surface mass transport can be efficiently suppressed by low-concentration polymers. Surface-grating decay has been measured for OTP containing 1 wt % polystyrene (PS, Mw = 1-8 kg/mol), which is miscible with OTP. The additive has no significant effect on the decay kinetics in the viscous-flow regime, but a significant effect in the surface-diffusion regime. In the latter case, surface evolution slows down and becomes nonexponential (decelerating over time). The effect increases with falling temperature and the molecular weight of PS. These results are attributed to the very different mobility of PS (slow) and OTP (fast) and their segregation during surface evolution, and relevant for understanding the surface mobility of multicomponent amorphous materials. PMID- 27267906 TI - Persistent misconceptions about HIV transmission among males and females in Malawi. AB - BACKGROUND: The prevalence of HIV in Malawi is one of the highest in sub-Saharan Africa, and misconceptions about its mode of transmission are considered a major contributor to the continued spread of the virus. METHODS: Using the 2010 Malawi Demographic and Health Survey, the current study explored factors associated with misconceptions about HIV transmission among males and females. RESULTS: We found that higher levels of ABC prevention knowledge were associated with lower likelihood of endorsing misconceptions among females and males (OR = 0.85, p < 0.001; OR = 0.85, p < 0.001, respectively). Compared to those in the Northern region, both females and males in the Central (OR = 0.54, p < 0.001; OR = 0.53, p < 0.001, respectively) and Southern regions (OR = 0.49, p < 0.001; OR = 0.43, p < 0.001, respectively) were less likely to endorse misconceptions about HIV transmission. Moreover, marital status and ethnicity were significant predictors of HIV transmission misconceptions among females but not among males. Also, household wealth quintiles, education, religion, and urban-rural residence were significantly associated with endorsing misconceptions about HIV transmission. CONCLUSION: Based on our findings, we recommend that education on HIV transmission in Malawi should integrate cultural and ethnic considerations of HIV/AIDS. PMID- 27267910 TI - Phenotypic and Signaling Consequences of a Novel Aberrantly Spliced Transcript FGF Receptor-3 in Hepatocellular Carcinoma. AB - Fibroblast growth factor receptor 3 (FGFR3) plays important roles in cell proliferation, differentiation, and angiogenesis. FGFR3 is abnormally upregulated in hepatocellular carcinoma (HCC), where it correlates positively with clinicopathologic index, HCC differentiation, and advanced nuclear grade. In this study, we describe an aberrantly spliced transcript of FGFR3, termed FGFR3Delta7 9, was identified as a high frequency even in HCC. FGFR3Delta7-9 lacks exons encoding the immunoglobulin-like III domain and promoted the proliferation, migration, and metastasis of HCC cells both in vitro and in vivo Coimmunoprecipation and surface plasmon resonance assays demonstrated that the binding affinity of the aberrant FGFR3Delta7-9 receptor to FGFs was significantly higher than wild-type FGFR3IIIc Furthermore, FGFR3Delta7-9 could be self activated by homodimerization and autophosphorylation even in the absence of ligand. Finally, FGFR3Delta7-9 more potently induced phosphorylation of the ERK and AKT kinases, leading to abnormal downstream signaling through the ERK and PI3K/AKT/mTOR pathways. FGFR3Delta7-9 also upregulated the metastasis-associated molecules Snail, MMP-9, and downregulated E-cadherin, which associated directly with FGFR3Delta7-9 Thus, as a ligand-dependent or -independent receptor, FGFR3Delta7-9 exerted multiple potent oncogenic functions in HCC cells, including proliferation, migration, and lung metastatic capacity. Overall, FGFR3 mRNA missplicing in HCC contributes significantly to its malignant character, with implications for therapeutic targeting. Cancer Res; 76(14); 4205-15. (c)2016 AACR. PMID- 27267911 TI - The effect of the National Health Insurance Scheme (NHIS) on health service delivery in mission facilities in Ghana: a retrospective study. AB - BACKGROUND: In 2004, Ghana began implementation of a National Health Insurance Scheme (NHIS) to minimize out-of-pocket expenditure at the point of use of service. The implementation of the scheme was accompanied by increased access and use of health care services. Evidence suggests most health facilities are faced with management challenges in the delivery of services. The study aimed to assess the effect of the introduction of the NHIS on health service delivery in mission health facilities in Ghana. We conceptualised the effect of NHIS on facilities using service delivery indicators such as outpatient and inpatient turn out, estimation of general service readiness, revenue and expenditure, claims processing and availability of essential medicines. We collected data from 38 mission facilities, grouped into the three ecological zones; southern, middle and northern. Structured questionnaires and exit interviews were used to collect data for the periods 2003 and 2010. The data was analysed in SPSS and MS Excel. RESULTS: The facilities displayed high readiness to deliver services. There were significant increases in outpatient and inpatient attendance, revenue, expenditure and improved access to medicines. Generally, facilities reported increased readiness to deliver services. However, challenging issues around high rates of non-reimbursement of NHIS claims due to errors in claims processing, lack of feedback regarding errors, and lack of clarity on claims reporting procedures were reported. CONCLUSION: The implementation of the NHIS saw improvement and expansion of services resulting in benefits to the facilities as well as constraints. The constraints could be minimized if claims processing is improved at the facility level and delays in reimbursements also reduced. PMID- 27267912 TI - Molecular and phenotypic characterization of strains of Shigella sonnei isolated over 31 years suggests the circulation of two prevalent subtypes in Sao Paulo State, Brazil. AB - Shigella sonnei is an important causative agent of bacillary dysentery worldwide that has recently emerged in developing countries. However, there are few studies that have characterized strains ofS. sonnei isolated in Brazil. The aims of this study were to assess the presence of 12 virulence genes, the antimicrobial resistance profile against 16 drugs and the genotypic diversity of strains of S. sonnei isolated in this country. Seventy-two strains of S. sonnei isolated from human diarrhoeic faeces in Sao Paulo State, Brazil from 1983-2014 were studied. All of the strains contained the ipaH, iuc and sigA genes. The ipaBCD gene was detected in 19 % of the strains, the ial and virF genes in 18 % and the sen gene in 10 % of the strains. The set1A, set1B, pic,sepA and sat genes were not detected. A total of 42 (58.3 %) strains were resistant to trimethoprim sulfamethoxazole. Thirty (41.6 %) strains were resistant to tetracycline. The S. sonnei strains were grouped in two clusters called A and B by PFGE and ERIC-PCR, and the majority of the strains comprised in each cluster presented >=80 % similarity. In conclusion, the pathogenic potential of the strains studied was highlighted by the presence of important virulence genes. The high rates of resistance to trimethoprim-sulfamethoxazole and tetracycline are alarming once those drugs can be used in the treatment of shigellosis. The PFGE and ERIC-PCR results suggest that there are two prevalent subtypes in the studied strains of S. sonnei that differed little over 31 years and have been contaminating humans and causing diseases in Sao Paulo State, Brazil. PMID- 27267913 TI - Experiences of households using integrated malaria prevention in two rural communities in Wakiso district, Uganda: a qualitative study. AB - BACKGROUND: The integrated approach to malaria prevention which advocates use of several methods in a holistic manner is being explored to complement existing strategies. A pilot project that promoted integrated malaria prevention established 40 demonstration households using the approach. As part of impact evaluation of the project 2 years after implementation, the experiences of these households using integrated malaria prevention were assessed. METHODS: A qualitative cross-sectional survey was carried out in Wakiso district, Uganda which involved 40 in-depth interviews among households implementing integrated malaria prevention. The study assessed practices on malaria prevention, benefits and challenges of using integrated malaria prevention, preference of malaria prevention methods, and impact of the demonstration households on the community. Thematic analysis was employed using Atlas ti software. RESULTS: The households continued to use many of the malaria prevention methods in the integrated approach including sleeping under long-lasting insecticidal nets, screening in windows and ventilators, removing mosquito breeding sites, and closing of doors early in the evenings. The major benefits reported from using integrated malaria prevention were reduction in mosquito populations in their houses and less occurrence of malaria particularly among children. Although several community members learnt about and admired various malaria prevention methods from the demonstration households especially screening in windows and ventilators, the majority could not afford to implement some of them due to lack of resources. The main challenge established in using integrated malaria prevention was the much time required to implement the several methods some of which had to be done regularly such as early closing of windows. In addition, complacency had led to some households not utilizing a number of methods in the integrated approach because of using others. CONCLUSION: Use of the integrated approach to malaria prevention benefited the demonstration households mainly through observed reduction in mosquitoes indoors and malaria occurrence hence could be promoted in other areas. Other studies to quantify the protective effect of integrated malaria prevention particularly regarding malaria prevalence and contribution of each of the methods are required. PMID- 27267914 TI - Soluble Siglec-9 suppresses arthritis in a collagen-induced arthritis mouse model and inhibits M1 activation of RAW264.7 macrophages. AB - BACKGROUND: The aim of this study was to assess the effects of soluble sialic acid-binding immunoglobulin-type lectin (sSiglec)-9 on joint inflammation and destruction in a murine collagen-induced arthritis (CIA) model and in monolayer cultures of murine macrophages (RAW264.7 cells and peritoneal macrophages) and fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis. METHODS: DBA/1J mice were immunized with type II collagen. Effects of sSiglec-9 were evaluated using a physiologic arthritis score, histological analysis, serum tumor necrosis factor (TNF)-alpha concentration, and the proportion of forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. In vivo biofluorescence imaging was used to assess the distribution of sSiglec-9. Levels of M1 (TNF-alpha, interleukin [IL]-6, and inducible nitric oxide synthase) and M2 (CD206, Arginase-1, and IL-10) macrophage markers and phosphorylation of intracellular signaling molecules were examined in macrophages, and levels of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 were examined in FLS. RESULTS: sSiglec-9 significantly suppressed the clinical and histological incidence and severity of arthritis. The proportion of Foxp3-positive Treg cells significantly improved and serum TNF-alpha concentration decreased in vivo. Although sSiglec-9 reduced the expression of M1 markers in macrophages, it did not affect the expression of M2 markers and MMPs in FLS. Nuclear factor (NF)-kB p65 phosphorylation was attenuated by sSiglec-9, and chemical blockade of the NF kB pathway reduced M1 marker expression in RAW264.7 cells. CONCLUSIONS: In this study, we have demonstrated the therapeutic effects of sSiglec-9 in a murine CIA model. The mechanism underlying these effects involves the suppression of M1 proinflammatory macrophages by inhibiting the NF-kB pathway. sSiglec-9 may provide a novel therapeutic option for patients with rheumatoid arthritis refractory to currently available drugs. PMID- 27267915 TI - Prevalence of patients receiving renal replacement therapy in El Salvador in 2014. AB - : El Salvador has the highest renal failure mortality rate in the Americas. Five healthcare providers offer renal replacement therapy (RRT) in the country. The national RRT prevalence has never been reported. AIMS: To determine the RRT prevalence in El Salvador and some basic characteristics. METHODS: The association of nephrology coordinated a nationwide cross-sectional survey during the third quarter of 2014. 31 renal centres participated in the survey, covering 99.5% of patients. RESULTS: National RRT prevalence: 595 per million population (pmp), N=3807, average age 50.4 years, 67.5% male. By modality: peritoneal dialysis (PD) 289 pmp, haemodialysis (HD) 233 pmp, with functioning kidney transplantation 74 pmp (living donor only). Social security covers 25% of the population but treats 49.7% of RRT patients. Generally, higher prevalence was observed in municipalities with renal centres or located on the coast or lowlands. Ninety-five percent of HD patients receive fewer than 3 weekly sessions. Of PD patients, 59% do not belong to a continuous outpatient or automated programme, and 25% still use rigid catheter. Aetiology of chronic kidney disease: unavailable/undetermined 50%, hypertension 21.1%, diabetes 18.9%, glomerulonephritis 6.7%, obstructive causes 1.2%, tubulointerstitial 0.9%, polycystic 0.4% and other 0.7%. DISCUSSION: Despite the increase in RRT services, the prevalence is lower than the Latin American average (660 pmp). Three quarters of HD and PD patients are under-dialysed. Obsolete RRT techniques are still used. The presence of Mesoamerican nephropathy influences the demographic characteristics (many young patients, two-thirds male, high prevalence in lowlands and coastlands). PMID- 27267916 TI - Immune response and histology of humoral rejection in kidney transplantation. AB - The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. PMID- 27267917 TI - Sudden cardiac death in non-dialysis chronic kidney disease patients. AB - BACKGROUND: A relatively high proportion of deaths in dialysis patients occur suddenly and unexpectedly. The incidence of sudden cardiac death (SCD) in non dialysis advanced chronic kidney disease (CKD) stages has been less well investigated. OBJECTIVE: This study aims to determine the incidence and predictors of SCD in a cohort of 1078 patients with CKD not yet on dialysis. METHODS: Prospective observational cohort study, which included patients with advanced CKD not yet on dialysis (stage 4-5). The association between baseline variables and SCD was assessed using Cox and competing-risk (Fine and Grey) regression models. Demographic, clinical information, medication use, and baseline biochemical parameters of potential interest were included as covariates. RESULTS: During the study period (median follow-up time 12 months), 210 patients died (19%), and SCD occurred in 34 cases (16% of total deaths). All cause mortality and SCD incidence rates were 113 (95% CI: 99-128), and 18 (95% CI: 13-26) events per 1000 patients/year, respectively. By Cox regression analysis, covariates significantly associated with SCD were: Age, comorbidity index, and treatment with antiplatelet drugs. This latter covariate showed a beneficial effect over the development of SCD. By competing-risk regression, in which the competing event was non-sudden death from any cause, only age and comorbidity index remained significantly associated with SCD. CONCLUSIONS: SCD is relatively common in non-dialysis advanced CKD patients. SCD was closely related to age and comorbidity, and some indirect data from this study suggest that unrecognised or undertreated cardiovascular disease may predispose to a higher risk of SCD. PMID- 27267918 TI - Hyperchloremia - Why and how. AB - Hyperchloremia is a common electrolyte disorder that is associated with a diverse group of clinical conditions. The kidney plays an important role in the regulation of chloride concentration through a variety of transporters that are present along the nephron. Nevertheless, hyperchloremia can occur when water losses exceed sodium and chloride losses, when the capacity to handle excessive chloride is overwhelmed, or when the serum bicarbonate is low with a concomitant rise in chloride as occurs with a normal anion gap metabolic acidosis or respiratory alkalosis. The varied nature of the underlying causes of the hyperchloremia will, to a large extent, determine how to treat this electrolyte disturbance. PMID- 27267919 TI - Autoantibodies against alternative complement pathway proteins in renal pathologies. AB - Complement system activation plays an important role in several renal pathologies, including antibody-mediated glomerulonephritis, ischaemia reperfusion injury of trasplanted kidneys or renal allograft rejection. Besides these conditions, alternative pathway abnormalities are directly involved in the pathogenesis of C3 glomerulopathies and atypical haemolytic uraemic syndrome. These abnormalities may be inherited or acquired, the latter as autoantibodies directed against the various components and regulators of the alternative complement pathway. The functional consequences of some of these antibodies and their association with these conditions are well known, whereas for other antibodies only isolated cases have been reported. This article describes the autoantibodies that target the alternative complement pathway proteins, their characteristics and their clinical relevance in renal pathologies. PMID- 27267920 TI - Risk factors associated with hernias on peritoneal dialysis. PMID- 27267921 TI - Musculoskeletal pain in patients with chronic kidney disease. AB - INTRODUCTION: Chronic musculoskeletal pain (CMP) is a very common symptom in patients with chronic kidney disease (CKD), and is associated with a significant deterioration in quality of life. AIMS: To determine the prevalence and clinical characteristics associated with CMP in patients with advanced CKD not on dialysis, and to analyse their relation with other uraemic symptoms and their prognosis significance. MATERIAL AND METHODS: Cross-sectional study to analyse the uraemic symptoms of an unselected cohort of patients with CKD stage 4-5 pre dialysis. In order to characterise patients with CMP, demographic and anthropometric data were collected, as well as data on comorbidities and kidney function. In addition, inflammatory parameters, uric parameters, bone mineral metabolism including 25-hydroxycholecalciferol (25-OHCC), creatine kinase and drugs of potential interest including allopurinol, statins and erythropoiesis stimulating agents were recorded. RESULTS: The study group consisted of 1169 patients (mean age 65+/-15 years, 54% male). A total of 38% of patients complained of CMP, and this symptom was more prevalent in women than in men (49 vs. 28%; P<.0001). Muscle weakness, pruritus, muscle cramps, ecchymosis, insomnia, oedema and dyspnoea were the most common symptoms associated with CMP. There were no significant associations between serum levels of creatine kinase, 25-OHCC, treatment with allopurinol, statins or erythropoiesis-stimulating agents and CMP. The female gender, elderly age, obesity, comorbidity (mainly diabetes, heart failure or COPD), and elevated levels of inflammatory markers (C-reactive protein and non-neutrophilic leukocytes) were the best determinants of CMP. While patients with CMP showed a worse survival rate, a multivariate analysis adjusted for demographic data ruled out the independent association of CMP with mortality. CONCLUSIONS: CMP is highly prevalent in patients with advanced CKD and is associated with other common symptoms of chronic uraemia. As with the general population, elderly age, the female gender, obesity and some comorbid conditions are the best determinants of CMP. Increased inflammatory markers commonly observed in patients with CMP may have a relevant role in its pathogenesis. PMID- 27267922 TI - Intestinal metaplasia of the bladder in 89 patients: a study with emphasis on long-term outcome. AB - BACKGROUND: Intestinal metaplasia of the bladder is an uncommon glandular proliferation. We examined a large series of intestinal metaplasia for the clinicopathological features and discuss the significance of this lesion. METHODS: All cases of intestinal metaplasia diagnosed in our institution between 1990 and 2014 were retrospectively reviewed. Patients with a history of urothelial carcinoma or concurrent adenocarcinoma were excluded. Patient characteristics, pathological features, and follow-up outcomes were obtained. RESULTS: We identified 89 patients with intestinal metaplasia during this period. Sixty seven were men and 22 were women. Mean age at diagnosis was 57 years (range 23-81). Common presenting complaints included haematuria (73 cases), mucosuria (13 cases), and irritative voiding symptoms (seven cases). The majority of intestinal metaplasias located on or near the trigone (67 cases). Eighty-two patients underwent transurethral resection of their lesions. Partial cystectomy was performed in the remaining seven patients. The mean follow-up of 78 patients was 105 months (range 6-255). One case of bladder adenocarcinoma was indentified 6 months later. The initial histologic findings had revealed intestinal metaplasia with severe dysplasia. Four patients presented recurrence during the follow-up, and this occurred 9, 13, 17 and 24 months after the surgery. CONCLUSIONS: Although intestinal metaplasia can be treated effectively by transurethral resection in most cases, its potential malignancy need to be taken into consideration after the evidence of recurrences and its association with bladder adenocarcinoma. Therefore, it is necessary to perform close surveillance following the surgery, particularly in patients with dysplastic changes. PMID- 27267923 TI - Religious beliefs and practices in pregnancy and labour: an inductive qualitative study among post-partum women in Ghana. AB - BACKGROUND: Religiosity in health care delivery has attracted some attention in contemporary literature. The religious beliefs and practices of patients play an important role in the recovery of the patient. Pregnant women and women in labour exhibit their faith and use religious artefacts. This phenomenon is poorly understood in Ghana. The study sought to investigate the religious beliefs and practices of post-partum Ghanaian women. METHODS: A descriptive phenomenological study was conducted inductively involving 13 women who were sampled purposively. Individual in-depth interviews were conducted in English, Ga, Twi and Ewe. The interviews were audio-taped and transcribed. Concurrent analysis was done employing the principles of content analysis. Ethical approval was obtained for the study and anonymity and confidentiality were ensured. RESULTS: Themes generated revealed religious beliefs and practices such as prayer, singing, thanksgiving at church, fellowship and emotional support. Pastors' spiritual interventions in pregnancy included prayer and revelations, reversing negative dreams, laying of hands and anointing women. Also, traditional beliefs and practices were food and water restrictions and tribal rituals. Religious artefacts used in pregnancy and labour were anointing oil, blessed water, sticker, blessed white handkerchief, blessed sand, Bible and Rosary. Family influence and secrecy were associated with the use of artefacts. CONCLUSIONS: Religiosity should be a key component of training health care professionals so that they can understand the religious needs of their clients and provide holistic care. We concluded that pregnant women and women in labour should be supported to exercise their religious beliefs and practices. PMID- 27267924 TI - Use of MicroRNA biomarkers to distinguish enchondroma from low-grade chondrosarcoma. AB - Establishing a definitive diagnosis between benign enchondroma versus low-grade chondrosarcoma presents a potential challenge to both clinicians and pathologists. microRNAs (small non-coding RNAs) have proven to be effective biomarkers for the identification of tumors and tumor progression. We present analysis, both array and quantitative PCR, that shows consistently and substantially increased expression of two microRNAs, miRs-181a and -138, in low grade chondrosarcomas compared with enchondromas. The data suggest these microRNAs would provide an analytical distinction between the chondrosarcoma and benign neoplasms that can be performed in formalin-fixed paraffin-embedded specimens. Together with recent publications, these data indicate that miRs-181a and -138 also play a role in tumor development and homeostasis and may provide new targets for the development of much needed therapeutic intervention. PMID- 27267925 TI - Sixty seconds on . . . Government research. PMID- 27267926 TI - Gigwa-Genotype investigator for genome-wide analyses. AB - BACKGROUND: Exploring the structure of genomes and analyzing their evolution is essential to understanding the ecological adaptation of organisms. However, with the large amounts of data being produced by next-generation sequencing, computational challenges arise in terms of storage, search, sharing, analysis and visualization. This is particularly true with regards to studies of genomic variation, which are currently lacking scalable and user-friendly data exploration solutions. DESCRIPTION: Here we present Gigwa, a web-based tool that provides an easy and intuitive way to explore large amounts of genotyping data by filtering it not only on the basis of variant features, including functional annotations, but also on genotype patterns. The data storage relies on MongoDB, which offers good scalability properties. Gigwa can handle multiple databases and may be deployed in either single- or multi-user mode. In addition, it provides a wide range of popular export formats. CONCLUSIONS: The Gigwa application is suitable for managing large amounts of genomic variation data. Its user-friendly web interface makes such processing widely accessible. It can either be simply deployed on a workstation or be used to provide a shared data portal for a given community of researchers. PMID- 27267927 TI - L1CAM: Cell adhesion and more. AB - L1CAM is a cell adhesion molecule of the immunoglobulin superfamily which was originally discovered as a major player in the development of the nervous system. L1CAM was demonstrated to have prognostic value in different cancers and to be a promising target for anti-cancer therapy. Here we overview the present data on L1CAM structure and function, regulation of its expression, role in cancer and therapeutic potential. PMID- 27267928 TI - The challenge of proving the existence of metazoan life in permanently anoxic deep-sea sediments. AB - The demonstration of the existence of metazoan life in absence of free oxygen is one of the most fascinating and difficult challenges in biology. Danovaro et al. (2010) discovered three new species of the Phylum Loricifera, living in the anoxic sediments of the L'Atalante, a deep-hypersaline anoxic basin of the Mediterranean Sea. Multiple and independent analyses based on staining, incorporation of radiolabeled substrates, CellTracker Green incorporation experiments and ultra-structure analyses, allowed Danovaro et al. (2010) to conclude that these animals were able to spend their entire life cycle under anoxic conditions. Bernhard et al. (2015) investigated the same basin. Due to technical difficulties in sampling operations, they could not collect samples from the permanently anoxic sediment, and sampled only the redoxcline portion of the L'Atalante basin. They found ten individuals of Loricifera and provided alternative interpretations of the results of Danovaro et al. (2010). Here we analyze these interpretations, and present additional evidence indicating that the Loricifera encountered in the anoxic basin L'Atalante were actually alive at the time of sampling. We also discuss the reliability of different methodologies and approaches in providing evidence of metazoans living in anoxic conditions, paving the way for future investigations.This paper is a response to Bernhard JM, Morrison CR, Pape E, Beaudoin DJ, Todaro MA, Pachiadaki MG, Kormas KAr, Edgcomb VG. 2015. Metazoans of redoxcline sediments in Mediterranean deep-sea hypersaline anoxic basins. BMC Biology 2015 13:105.See research article at http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-015-0213-6. PMID- 27267929 TI - Rhizobium leguminosarum symbiovar trifolii, Ensifer numidicus and Mesorhizobium amorphae symbiovar ciceri (or Mesorhizobium loti) are new endosymbiotic bacteria of Lens culinaris Medik. AB - A total of 142 rhizobial bacteria were isolated from root nodules of Lens culinaris Medik endemic to Tunisia and they belonged to the species Rhizobium leguminosarum, and for the first time to Ensifer and Mesorhizobium, genera never previously described as microsymbionts of lentil. Phenotypically, our results indicate that L. culinaris Medik strains showed heterogenic responses to the different phenotypic features and they effectively nodulated their original host. Based on the concatenation of the 16S rRNA with relevant housekeeping genes (glnA, recA, dnaK), rhizobia that nodulate lentil belonged almost exclusively to the known R. leguminosarum sv. viciae. Interestingly, R. leguminosarum sv. trifolii, Ensifer numidicus (10 isolates) and Mesorhizobium amorphae (or M. loti) (9 isolates) isolates species, not considered, up to now, as a natural symbiont of lentil are reported. The E. numidicus and M. amorphae (or M. loti) strains induced fixing nodules on Medicago sativa and Cicer arietinum host plants, respectively. Symbiotic gene phylogenies showed that the E. numidicus, new symbiont of lentil, markedly diverged from strains of R. leguminosarum, the usual symbionts of lentil, and converged to the symbiovar meliloti so far described within E. meliloti Indeed, the nodC and nodA genes from the M. amorphae showed more than 99% similarity with respect to those from M. mediterraneum, the common chickpea nodulating species, and would be included in the new infrasubspecific division named M. amorphae symbiovar ciceri, or to M. loti, related to the strains able to effectively nodulate C. arietinum host plant. On the basis of these data, R. leguminosarum sv. trifolii (type strain LBg3 (T)), M. loti or M. amorphae sv. ciceri (type strain LB4 (T)) and E. numidicus (type strain LBi2 (T)) are proposed as new symbionts of L. culinaris Medik. PMID- 27267930 TI - Methane release from sediment seeps to the atmosphere is counteracted by highly active Methylococcaceae in the water column of deep oligotrophic Lake Constance. AB - Methane emissions from freshwater environments contribute substantially to global warming but are under strong control of aerobic methane-oxidizing bacteria. Recently discovered methane seeps (pockmarks) in freshwater lake sediments have the potential to bypass this control by their strong outgassing activity. Whether this is counteracted by pelagic methanotrophs is not well understood yet. We used a (3)H-CH4-radiotracer technique and pmoA-based molecular approaches to assess the activity, abundance and community structure of pelagic methanotrophs above active pockmarks in deep oligotrophic Lake Constance. Above profundal pockmarks, methane oxidation rates (up to 458 nmol CH4 l(-1) d(-1)) exceeded those of the surrounding water column by two orders of magnitude and coincided with maximum methanotroph abundances of 0.6% of the microbial community. Phylogenetic analysis indicated a dominance of members of the Methylococcaceae in the water column of both, pockmark and reference sites, with most of the retrieved sequences being associated with a water-column specific clade. Communities at pockmark and reference locations also differed in parts, which was likely caused by entrainment of sediment-hosted methanotrophs at pockmark sites. Our results show that the release of seep-derived methane to the atmosphere is counteracted by a distinct methanotrophic community with a pronounced activity throughout bottom waters. PMID- 27267931 TI - Subalpine conifers in different geographical locations host highly similar foliar bacterial endophyte communities. AB - Pines in the subalpine environment at Niwot Ridge, CO, have been found to host communities of acetic acid bacteria (AAB) within their needles. The significance and ubiquity of this pattern is not known, but recent evidence of nitrogen (N) fixing activity in Pinus flexilis (limber pine) foliage calls for a better understanding of the processes that regulate endophytic communities in forest tree canopies. Here, to test if AAB dominate the foliar bacterial microbiota in other subalpine locations, we compared the 16S rRNA community in needles from P. flexilis and P. contorta (lodgepole pine) growing in the Eastern Sierra Nevada, CA, and Niwot Ridge, CO. AAB made up the majority of the bacterial community in both species at both sites. Multiple distinct AAB taxa, resolved at the single nucleotide level, were shared across host species and sites, with dominant OTUs identical or highly similar to database sequences from cold environments, including high altitude air sampled in Colorado, and the endosphere of Arctic plants. Our results suggest strong selection for community composition, potentially amplified by the long lifespan of individual Pinus needles, along with low dispersal constraints on canopy bacteria. PMID- 27267933 TI - Tofacitinib for the treatment of psoriasis. AB - INTRODUCTION: The identification of a number of psoriasis-susceptibility genes and a better understanding of the pathogenesis of the intracellular metabolic pathways, have generated new perspectives on psoriasis treatment, in particular new compounds that inhibit certain intracellular proteins involved in the immune response. In contrast to biologic agents, these compounds block intracellular targets such as transcriptional factors or enzymes. AREAS COVERED: Tofacitinib is a small molecule that acts as a reversible, competitive inhibitor of ATP in the ATP binding site of JAK proteins, determining their inactivation, thus prevents the downstream activation of the STAT proteins, which are then unable to up regulate the pro-inflammatory genes implicated in psoriasis. The authors present an overview of Phases I - III clinical trials of tofacitinib for psoriasis based on peer-reviewed literature. EXPERT OPINION: In clinical practice, it is important to assess the response of psoriasis to tofacitinib and identify possible clinical, genetic, and immune biomarkers to predict the response. Comorbidities associated with psoriasis, in particular metabolic syndrome and obesity, are also an important aspect of using tofacitinib in clinical practice. There are some evidences that a drug such as tofacitinib could be used to improve not only psoriasis, but also some of its important comorbidities. PMID- 27267932 TI - Benthic protists: the under-charted majority. AB - Marine protist diversity inventories have largely focused on planktonic environments, while benthic protists have received relatively little attention. We therefore hypothesize that current diversity surveys have only skimmed the surface of protist diversity in marine sediments, which may harbor greater diversity than planktonic environments. We tested this by analyzing sequences of the hypervariable V4 18S rRNA from benthic and planktonic protist communities sampled in European coastal regions. Despite a similar number of OTUs in both realms, richness estimations indicated that we recovered at least 70% of the diversity in planktonic protist communities, but only 33% in benthic communities. There was also little overlap of OTUs between planktonic and benthic communities, as well as between separate benthic communities. We argue that these patterns reflect the heterogeneity and diversity of benthic habitats. A comparison of all OTUs against the Protist Ribosomal Reference database showed that a higher proportion of benthic than planktonic protist diversity is missing from public databases; similar results were obtained by comparing all OTUs against environmental references from NCBI's Short Read Archive. We suggest that the benthic realm may therefore be the world's largest reservoir of marine protist diversity, with most taxa at present undescribed. PMID- 27267934 TI - Fermentation properties and potential prebiotic activity of Bimuno(r) galacto oligosaccharide (65 % galacto-oligosaccharide content) on in vitro gut microbiota parameters. AB - Prebiotic oligosaccharides have the ability to generate important changes in the gut microbiota composition that may confer health benefits to the host. Reducing the impurities in prebiotic mixtures could expand their applications in food industries and improve their selectivity and prebiotic effect on the potential beneficial bacteria such as bifidobacteria and lactobacilli. This study aimed to determine the in vitro potential fermentation properties of a 65 % galacto oligosaccharide (GOS) content Bimuno(r) GOS (B-GOS) on gut microbiota composition and their metabolites. Fermentation of 65 % B-GOS was compared with 52 % B-GOS in pH- and volume-controlled dose-response anaerobic batch culture experiments. In total, three different doses (1, 0.5 and 0.33 g equivalent to 0.1, 0.05 and 0.033 g/l) were tested. Changes in the gut microbiota during a time course were identified by fluorescence in situ hybridisation, whereas small molecular weight metabolomics profiles and SCFA were determined by 1H-NMR analysis and GC, respectively. The 65 % B-GOS showed positive modulation of the microbiota composition during the first 8 h of fermentation with all doses. Administration of the specific doses of B-GOS induced a significant increase in acetate as the major SCFA synthesised compared with propionate and butyrate concentrations, but there were no significant differences between substrates. The 65 % B-GOS in syrup format seems to have, in all the analysis, an efficient prebiotic effect. However, the applicability of such changes remains to be shown in an in vivo trial. PMID- 27267936 TI - Synthesis of Cyclic Porphyrin Trimers through Alkyne Metathesis Cyclooligomerization and Their Host-Guest Binding Study. AB - Cyclic porphyrin trimers were synthesized through one-step cyclooligomerization via alkyne metathesis from diyne monomers. These macrocycles show interesting host-guest binding interactions with fullerenes, selectively binding C70 (6 * 10(3) M(-1)) over C60 and C84 (no binding observed). The fullerene-encapsulated host-guest complex can undergo guest or host exchange in the presence of another guest (2,4,6-tri(4-pyridyl)-1,3,5-triazine) or host (cage COP5) molecule with higher binding affinity. PMID- 27267935 TI - A factor analysis of the meanings of anorexia nervosa: intrapsychic, relational, and avoidant dimensions and their clinical correlates. AB - BACKGROUND: Anorexia nervosa (AN) is a difficult to treat disorder characterized by ambivalence towards recovery and high mortality. Eating symptomatology has a sort of adaptive function for those who suffer from AN but no studies have to date investigated the relationship between the reported meanings of AN and patients' clinical characteristics. Therefore, we aimed to perform a factor analysis of a new measure testing its psychometric properties in order to clarify whether subjective meanings of AN can be related to AN severity, to ascertain if some personality traits correlate with the meanings attributed to AN by patients, and finally to verify to what extent such meanings relate to patients' duration of both illness and treatment. METHODS: Eighty-one inpatients affected by AN were recruited for this study and clinical data were recorded. Participants were asked to complete a novel instrument, the Meanings of Anorexia Nervosa Questionnaire (MANQ) focused on the measurement of values that patients attribute to AN and other measures as follows: Eating Disorders Inventory-2, Beck Depression Inventory, Temperament and Character Inventory, and Anorexia Nervosa Stages of Change Questionnaire. RESULTS: As measured by the MANQ, body dissatisfaction, problems of adolescence, and distress at school or work mainly triggered the onset of AN. Balance and self-control were mostly reported as meanings of AN while the most frequent negative effects were: being controlled by the illness, obsessive thoughts about body shape, and feeling alone. Differences were found between diagnostic subtypes. When a factorial analysis was performed, three factors emerged: intrapsychic (e.g., balance/safety, self-control, control/power, way to be valued), relational (e.g., communication, way to be recognized), and avoidant (e.g., the avoidance of negative feelings, emotions, and experiences). These factors correlated with patients' personality and motivation to treatments but were unrelated to duration of both illness and treatments. CONCLUSIONS: Given the ego-syntonic nature of AN, the understanding of patients' value of their disorder could be relevant in treatment; moreover, the positive value of AN resulted to be unrelated to the duration of both illness and treatments. Future research is warranted to replicate these findings and test their clinical implications. PMID- 27267937 TI - Performativity Double Standards and the Sexual Orientation Climate at a Southern Liberal Arts University. AB - This study employs quantitative and qualitative methods to examine how heterosexual, bisexual, and gay students rate and describe a Southern, religiously affiliated university's sexual orientation climate. Using qualitative data, queer theory, and the concept tyranny of sexualized spaces, we explain why non-heterosexual students have more negative perceptions of the university climate than heterosexual male students, in both bivariate and multivariate analyses. Although heterosexual students see few problems with the campus sexual orientation climate, bisexual men and women describe being challenged on the authenticity of their orientation, and lesbian and, to a greater extent, gay male students report harassment and exclusion in a number of settings. These distinct processes are influenced by broader heteronormative standards. We also shed much needed light on how gendered sexual performativity double standards within an important campus microclimate (fraternity parties) contribute to creating a tyrannical sexualized space and negatively affect overall campus climate perceptions. PMID- 27267938 TI - Influence of Surface Treatment on Magnetic Properties of Fe3O4 Nanoparticles Synthesized by Electrochemical Method. AB - The changes of magnetic properties in magnetite nanoparticles during two different stabilization processes were investigated. Magnetic nanoparticles (MNPs) were obtained by electrochemical synthesis from two kinds of salts: (CH3)4NCl and NaCl. After that, two methods-steric and electrostatic-were used to stabilize MNPs with oleic acid (OA) and sodium hydroxide (NaOH), respectively. As a consequence, aqueous and organic dispersions were obtained after surface modification. The coated nanoparticles were characterized by TEM, zeta potential, thermogravimetry analysis (TGA), cyclic voltammetry (CV), magnetization measurements, and infrared and Mossbauer spectroscopy. The results showed that the particles were between 8 and 13 nm in size. In addition, the MNPs were coated with negative charge layers from NaOH by physisorption and coated with carboxylate groups from OA by the chemisorption process, and hence, they exhibited different reactivity and behavior depending on the nature of the electrolyte used in the electrochemical synthesis. Furthermore, the uncoated and coated MNPs had a narrow size distribution. Additionally, the saturation magnetization values showed dependence on the magnetite synthesis conditions and surface modifiers. PMID- 27267939 TI - Inhibition of Fat Accumulation by Hesperidin in Caenorhabditis elegans. AB - Hesperidin, abundant in citrus fruits, has a wide range of pharmacological effects, including anticarcinogenic, anti-inflammatory, antioxidative, radioprotective, and antiviral activities. However, relatively few studies on the effects of hesperidin on lipid metabolism have been reported. Here, using Caenorhaditis elegans as a model animal, we found that 100 MUM hesperidin significantly decreased fat accumulation in both high-fat worms cultured in nematode growth medium containing 10 mM glucose (83.5 +/- 1.2% versus control by Sudan Black B staining and 87.6 +/- 2.0% versus control by Oil Red O staining; p < 0.001) and daf-2 mutant worms (87.8 +/- 1.4% versus control by Oil Red O staining; p < 0.001). Furthermore, 50 MUM hesperidin decreased the ratio of oleic acid/stearic acid (C18:1Delta9/C18:0) (p < 0.05), and supplementation of oleic acid could restore the inhibitory effect of hesperidin on fat accumulation. Hesperidin significantly downregulated the expression of stearoyl-CoA desaturase, fat-6, and fat-7 (p < 0.05), and mutation of fat-6 and fat-7 reversed fat accumulation inhibited by hesperidin. In addition, hesperidin decreased the expression of other genes involved in lipid metabolism, including pod-2, mdt-15, acs-2, and kat-1 (p < 0.05). These results suggested that hesperidin reduced fat accumulation by affecting several lipid metabolism pathways, such as fat-6 and fat-7. This study provided new insights into elucidating the mechanism underlying the regulation of lipid metabolism by hesperidin. PMID- 27267940 TI - Noninvasive Ventilation and Clinical Outcome. PMID- 27267941 TI - Detection of differential DNA methylation in repetitive DNA of mice and humans perinatally exposed to bisphenol A. AB - Developmental exposure to bisphenol A (BPA) has been shown to induce changes in DNA methylation in both mouse and human genic regions; however, the response in repetitive elements and transposons has not been explored. Here we present novel methodology to combine genomic DNA enrichment with RepeatMasker analysis on next generation sequencing data to determine the effect of perinatal BPA exposure on repetitive DNA at the class, family, subfamily, and individual insertion level in both mouse and human samples. Mice were treated during gestation and lactation to BPA in chow at 0, 50, or 50,000 ng/g levels and total BPA was measured in stratified human fetal liver tissue samples as low (non-detect to 0.83 ng/g), medium (3.5 to 5.79 ng/g), or high (35.44 to 96.76 ng/g). Transposon methylation changes were evident in human classes, families, and subfamilies, with the medium group exhibiting hypomethylation compared to both high and low BPA groups. Mouse repeat classes, families, and subfamilies did not respond to BPA with significantly detectable differential DNA methylation. In human samples, 1251 individual transposon loci were detected as differentially methylated by BPA exposure, but only 19 were detected in mice. Of note, this approach recapitulated the discovery of a previously known mouse environmentally labile metastable epiallele, Cabp(IAP). Thus, by querying repetitive DNA in both mouse and humans, we report the first known transposons in humans that respond to perinatal BPA exposure. PMID- 27267942 TI - Capillary lactate concentration on admission of normotensive trauma patients: a prospective study. AB - BACKGROUND: Elevated serum blood lactate is an indicator of on-going bleeding in severe trauma patients. Point-of-care (POC) capillary lactate measurement devices may be useful to rapidly assess lactate concentration at the bedside. The aim of this study was to test the diagnostic performance of capillary lactate to predict significant transfusion in normotensive trauma patients. METHODS: We conducted a prospective observational study in one level-I trauma centre. From August 2011 to February 2013, 120 consecutive adult patients with systolic blood pressure (SBP) higher than 90 mmHg were included. Capillary lactate was measured on admission in the trauma bay. The primary outcome was defined as a significant transfusion within the first 48 h. Diagnostic performance was determined using receiver operating characteristic (ROC) curve analysis. We also tested the agreement between capillary lactate and blood lactate concentrations using Bland and Altman analysis. RESULTS: Of the 120 normotensive trauma patients, 30 (25 %) required at least one unit of packed red blood cells (RBC) and 12 (10 %) patients received at least four RBC within the first 48 h. All patients with significant RBC transfusion had capillary lactate higher than 3.5 mmol/l. The area under the ROC curve of capillary lactate on admission to predict transfusion of at least 4 RBC units was 0.68 [95 % CI 0.58 - 0.78]. The average bias between capillary and blood lactate measurements was 2.4 mmol/l with a standard deviation of 3.0 mmol/l (n = 60 patients). CONCLUSIONS: Although a significant association was found between POC lactate concentration and transfusion requirements, the diagnostic performance of capillary lactate measurements was poor. Due to large disagreement between capillary lactate and blood lactate, capillary lactate cannot be considered in the clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov, No. NCT01793428 . PMID- 27267944 TI - HPV genotypes detected in the oropharyngeal mucosa of HIV-infected men who have sex with men in Northern Italy. AB - The aim of this study was to investigate the epidemiological profile of HPV oropharyngeal infections in HIV-infected men who have sex with men. A total of 135 subjects were enrolled at the L. Sacco University Hospital (Milan, Italy) to evaluate their HPV oropharyngeal infection status at baseline and at a follow-up visit at least 12 months later. HPV DNA was detected from oropharyngeal swabs using an in-house nested PCR that amplifies a segment of the L1 gene. The PCR products were then sequenced and genotyped. A greater percentage of high-risk genotypes was identified compared to low-risk genotypes (13.7% vs. 6.9%, P < 0.05), and two uncommon alpha-HPV genotypes were detected, i.e. HPV-102 and HPV 114. HPV infection prevalence was 24.4% and the cumulative incidence was 24.1%. During the follow-up period, one case of HPV infection (HPV-33) persisted, while the overall rate of infection clearance was 58.3%. HPV oropharyngeal infection was widespread in the cohort examined, and most of the infections were transient and cleared within 12 months. These results may help to clarify the role of HPV in the oropharynx and may also improve our understanding of the need to implement preventive strategies in at-risk populations. PMID- 27267943 TI - Multimorbidity and use of hypnotic and anxiolytic drugs: cross-sectional and follow-up study in primary healthcare in Iceland. AB - BACKGROUND: The prevalence of multimorbidity is increasing worldwide, presumably leading to an increased use of medicines. During the last decades the use of hypnotic and anxiolytic benzodiazepine derivatives and related drugs has increased dramatically. These drugs are frequently prescribed for people with a sleep disorder often merely designated as "insomnia" in the medical records and lacking a clear connection with the roots of the patients' problems. Our aim was to analyse the prevalence of multimorbidity in primary healthcare in Iceland, while concurrently investigating a possible association with the prevalence and incidence of hypnotic/anxiolytic prescriptions, short-term versus chronic use. METHODS: Data were retrieved from a comprehensive database of medical records from primary healthcare in Iceland to find multimorbid patients and prescriptions for hypnotics and anxiolytics, linking diagnoses (ICD-10) and prescriptions (2009 2012) to examine a possible association. Nearly 222,000 patients, 83 % being local residents in the capital area, who contacted 16 healthcare centres served in total by 140 general practitioners, were set as a reference to find the prevalence of multimorbidity as well as the prevalence and incidence of hypnotic/anxiolytic prescriptions. RESULTS: The prevalence of multimorbidity in the primary care population was 35 %, lowest in the young, increasing with age up to the 80+ group where it dropped somewhat. The prevalence of hypnotic/anxiolytic prescriptions was 13.9 %. The incidence rate was 19.4 per 1000 persons per year in 2011, and 85 % of the patients prescribed hypnotics/anxiolytics were multimorbid. Compared to patients without multimorbidity, multimorbid patients were far more likely to be prescribed a hypnotic and/or an anxiolytic, OR = 14.9 (95 % CI = 14.4-15.4). CONCLUSIONS: Patients with multiple chronic conditions are common in the primary care setting, and prevalence and incidence of hypnotic/anxiolytic prescriptions are high. Solely explaining use of these drugs by linear thinking, i.e. that "insomnia" leads to their prescription is probably simplistic, since the majority of patients prescribed these drugs are multimorbid having several chronic conditions which could lead to sleeping problems. However, multimorbidity as such is not an indication for hypnotics, and doctors should be urged to greater caution in their prescribing, bearing in mind non pharmacological therapy options. PMID- 27267949 TI - Preoperative oral immunonutrition versus standard preoperative oral diet in well nourished patients undergoing pancreaticoduodenectomy. AB - BACKGROUND: Pancreaticoduodenectomy is still associated to high morbility, especially due to pancreatic surgery related and infectious complications: many risk factors have already been advocated. Aim of this study is to evaluate the role of preoperative oral immunonutrition in well nourished patients scheduled for pancreaticoduodenectomy. METHODS: From February 2014 to June 2015, 54 well nourished patients undergoing pancreaticoduodenectomy were enrolled for 5 days preoperative oral immunonutrition. A series of consecutive patients submitted to the same intervention in the same department, with preoperative standard oral diet, was matched 1:1. For analysis demographic, pathological and surgical variables were considered. Mortality rate, overall postoperative morbility, pancreatic fistula, post pancreatectomy haemorrhage, delayed gastric emptying, infectious complications and length of hospital stay were described for each groups. Chi squared test, Fisher's Exact test and Student's T test were used for comparison. Differences were considered statistically significant at p < 0.05. Statistics was performed using a freeware Microsoft Excel ((r)) based program and SPSS v 10.00. RESULTS: No statistical differences in term of mortality (2.1% in each groups) and overall morbility rate (41.6% vs 47.9%) occurred between the groups as well as for pancreatic surgery related complications. Conversely, statistical differences were found for infectious complications (22.9% vs 43.7%, p = 0.034) and length of hospital stay (18.3 +/- 6.8 days vs 21.7 +/- 8.3, p = 0.035) in immunonutrition group. CONCLUSION: Preoperative oral immunonutrition is effective for well nourished patients scheduled for pancreaticoduodenectomy; it helps to reduce the risk of postoperative infectious complications and length of hospital stays. PMID- 27267948 TI - Diet Quality and Colorectal Cancer Risk in the Women's Health Initiative Observational Study. AB - Diet quality index scores on Healthy Eating Index 2010 (HEI-2010), Alternative HEI-2010, alternative Mediterranean Diet Index, and the Dietary Approaches to Stop Hypertension (DASH) index have been inversely associated with all-cause and cancer-specific death. This study assessed the association between these scores and colorectal cancer (CRC) incidence as well as CRC-specific mortality in the Women's Health Initiative Observational Study (1993-2012), a US study of postmenopausal women. During an average of 12.4 years of follow-up, there were 938 cases of CRC and 238 CRC-specific deaths. We estimated multivariate hazard ratios and 95% confidence intervals for relationships between quintiles of diet scores (from baseline food frequency questionnaires) and outcomes. HEI-2010 score (hazard ratios were 0.81, 0.77, and 0.73 with P values of 0.04, 0.01, and <0.01 for quintiles 3-5 vs. quintile 1, respectively) and DASH score (hazard ratios were 0.72, 0.74, and 0.78 with P values of <0.01, <0.01, and 0.03 for quintiles 3 5 vs. quintile 1, respectively), but not other diet scores, were associated with a lower risk of CRC in adjusted models. No diet scores were significantly associated with CRC-specific mortality. Closer adherence to HEI-2010 and DASH dietary recommendations was inversely associated with risk of CRC in this large cohort of postmenopausal women. PMID- 27267951 TI - A sham-controlled randomized trial of adjunctive light therapy for non-seasonal depression. AB - BACKGROUND: The aim of the study was to examine the efficacy and safety of morning bright light therapy (BLT) in the treatment of patients with a current major depressive episode (MDE) in bipolar and unipolar disorder without a seasonal pattern. It was a randomized, sham-controlled trial. METHODS: Adults, ages 18-70 years were randomized to treatment either with BLT or a sham negative ion generator (as a placebo control). The subjects were required to be on a stable and therapeutic dose of psychotropic medication for at least 4 weeks prior to enrollment and their treatment had to be insufficiently effective. Their clinical state was monitored at the baseline and at the end of treatment. The Hamilton Depression Rating Scale-21 items (HDRS-21), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Clinical Global Impression-Severity (CGI-S) and Patient Global Impression (PGI) were used. The results were analyzed with an intention-to-treat (ITT) analysis. RESULTS: Ninety five patients were enrolled (50 diagnosed with bipolar disorder and 45 with unipolar depression). Fifty-two patients were randomized to treatment with BLT and forty-three were in the placebo group (ITT population). Eighty-three subjects completed the study. There were 12 dropouts (5 in the light group and 7 in the placebo group). After 14 days of treatment, a significant improvement was found in all groups (p<0.001). The subjects treated with BLT did not significantly differ in terms of improvement in HDRS-21 scores at the endpoint when compared to patients treated with placebo (p=0.2). However, further analysis demonstrated significantly higher response (50% v. 27.9%, p=0.02) and remission rates (28.8% v. 11.6%, p=0.04) among patients treated with morning BLT when compared to placebo group. It should be noted that in the population of drug-resistant patients, BLT was more efficacious than placebo. There were no statistically significant differences between unipolar and bipolar disorders (p=0.4). CONCLUSION: Although overall improvement in HDRS-21 scores were not superior in the BLT group, both response and remission rates were significantly higher among patients treated with BLT relative to those receiving the sham intervention. BLT was also more efficacious than placebo in the population of patients with drug resistant depression. Further studies to define the subpopulation of patients with non-seasonal depression who may benefit the most from BLT are needed. PMID- 27267950 TI - Partial sleep deprivation impacts impulsive action but not impulsive decision making. AB - Sleep deprivation may lead to increased impulsivity, however, previous literature has focused on examining effects of total sleep deprivation (TSD) rather than the more common condition, partial sleep deprivation (PSD) or 'short sleep'. Moreover, it has been unclear whether PSD impacts impulse-related cognitive processes, and specifically if it differentially affects impulsive action versus impulsive decision-making. We sought to determine if short compared to long sleep (6 vs. 9h/night) impacts impulsive action via behavioral inhibition (Go/No-Go), and/or impulsive decision-making processes of risk taking (Balloon Analogue Risk Task [BART]) and preferences for immediate over delayed rewards (Delay Discounting). In a within-subject design, 34 participants (71% female, mean age=37.0years, SD=10.54) were assigned to four consecutive nights of 6h/night (short sleep) and 9h/night (long sleep) in their own home in random counterbalanced order. Sleep was measured via wrist-worn actigraphs to confirm adherence to the sleep schedules (mean short sleep=5.9h, SD=0.3; mean long sleep=8.6h, SD=0.3, p<0.001). The Go/No-Go, BART, and Delay Discounting tasks were completed following both sleep conditions. Participants had more inhibition errors on the Go/No-Go task after short (mean false alarms=19.79%, SD=14.51) versus long sleep (mean=15.97%, SD=9.51, p=0.039). This effect was strongest in participants reporting longer habitual time in bed (p=0.04). There were no differences in performance following long- versus short-sleep for either delay discounting or the BART (p's>0.4). Overall, these results indicate that four days of PSD diminishes behavioral inhibition abilities, but may not alter impulsive decision-making. These findings contribute to the emerging understanding of how partial sleep deprivation, currently an epidemic, impacts cognitive ability. Future research should continue to explore the connection between PSD and cognitive functions, and ways to minimize the occurrence and negative consequences of short sleep. PMID- 27267952 TI - Hostile interpretation bias in depression. AB - BACKGROUND: Research suggests an important relationship between interpretation bias, hostility and Major Depressive Disorder (MDD). Extant literature has yet to examine hostile interpretation bias in clinically depressed samples; the current studies sought to fill this gap. METHOD: Study 1 participants included undergraduates who met criteria for MDD (n=36) or no anxiety or mood diagnosis (n=35). Each participant completed a structured clinical interview along with measures of depression, hostile interpretation bias, and trait hostility. In Study 2, a sample of treatment-seeking individuals with elevated trait anger completed measures of depression, hostile interpretation bias, and trait anger. RESULTS: Study 1 demonstrated that, relative to the non-depressed group, individuals with depression displayed greater hostile interpretation bias but comparable levels of trait hostility. In Study 2, greater hostile interpretation bias was associated with greater depressive symptoms, and this relationship was independent of co-occurring trait anger. LIMITATIONS: The correlational nature of these studies precludes interpretation of causal relationships between constructs. Additionally, replication of these results should be sought in a larger, more diverse sample. CONCLUSION: Overall, the findings suggest hostile interpretation bias may play a unique role in depression and could be a treatable feature of interpersonal mechanisms maintaining MDD. PMID- 27267953 TI - A cross-sectional study of associations between casual partner, friend discrimination, social support and anxiety symptoms among Chinese transgender women. AB - Anxiety symptoms are the prevalent mental disorders for transgender women. However, only a few studies are available pertaining to this problem among Chinese Transgender women. Chinese Transgender women are a vulnerable population which is exposed to discrimination and loss of social support due to their gender identity and transition. This study was conducted to estimate the prevalence and factors associated with anxiety symptoms among Chinese transgender women. A cross sectional study was performed by convenience sampling. This comprised of 209 Chinese transgender women in Shenyang, China. The Zung Self-Rating Anxiety Scale (SAS) was used to assess anxiety symptoms for these transgender women. Hierarchical multiple regression analysis was performed to explore the associated factors of SAS. The prevalence of anxiety symptoms in Chinese transgender women was found to be 34.5%. Regression analyses indicated that SAS was associated with casual partnership, friend discrimination and social support in the final model. Sexual partnership and discrimination contributed the most to the model, R square, accounting for 19.2% and 15.5% of the total variance respectively. Chinese transgender women showed considerably high level of anxiety symptoms. It was also found that they were exposed to significant transition challenges, such as high risk sexual partnership, excessive discrimination and a reduction in social support. Furthermore, anxiety symptoms was best predicted by the absence or presence of a casual partner, friend discrimination and social support rather than the disclosure of their gender identity, knowledge of HIV prevention and health service. Improvement of social support, reduction of friend discrimination and determination of the characteristics of risky sexual partnerships especially for the casual partner can help to attenuate anxiety symptoms and increase mental well-being for transgender women. PMID- 27267954 TI - BDNF DNA methylation changes as a biomarker of psychiatric disorders: literature review and open access database analysis. AB - Brain-derived neurotrophic factor (BDNF) plays an important role in nervous system development and function and it is well established that BDNF is involved in the pathogenesis of a wide range of psychiatric disorders. Recently, numerous studies have associated the DNA methylation level of BDNF promoters with certain psychiatric phenotypes. In this review, we summarize data from current literature as well as from our own analysis with respect to the correlation of BDNF methylation changes with psychiatric disorders and address questions about whether DNA methylation related to the BDNF can be useful as biomarker for specific neuropsychiatric disorders. PMID- 27267955 TI - Designing Health Websites Based on Users' Web-Based Information-Seeking Behaviors: A Mixed-Method Observational Study. AB - BACKGROUND: Laypeople increasingly use the Internet as a source of health information, but finding and discovering the right information remains problematic. These issues are partially due to the mismatch between the design of consumer health websites and the needs of health information seekers, particularly the lack of support for "exploring" health information. OBJECTIVE: The aim of this research was to create a design for consumer health websites by supporting different health information-seeking behaviors. We created a website called Better Health Explorer with the new design. Through the evaluation of this new design, we derive design implications for future implementations. METHODS: Better Health Explorer was designed using a user-centered approach. The design was implemented and assessed through a laboratory-based observational study. Participants tried to use Better Health Explorer and another live health website. Both websites contained the same content. A mixed-method approach was adopted to analyze multiple types of data collected in the experiment, including screen recordings, activity logs, Web browsing histories, and audiotaped interviews. RESULTS: Overall, 31 participants took part in the observational study. Our new design showed a positive result for improving the experience of health information seeking, by providing a wide range of information and an engaging environment. The results showed better knowledge acquisition, a higher number of page reads, and more query reformulations in both focused and exploratory search tasks. In addition, participants spent more time to discover health information with our design in exploratory search tasks, indicating higher engagement with the website. Finally, we identify 4 design considerations for designing consumer health websites and health information-seeking apps: (1) providing a dynamic information scope; (2) supporting serendipity; (3) considering trust implications; and (4) enhancing interactivity. CONCLUSIONS: Better Health Explorer provides strong support for the heterogeneous and shifting behaviors of health information seekers and eases the health information-seeking process. Our findings show the importance of understanding different health information seeking behaviors and highlight the implications for designers of consumer health websites and health information-seeking apps. PMID- 27267957 TI - A novel mutation of ROBO3 in horizontal gaze palsy with progressive scoliosis. PMID- 27267956 TI - Chemical Dissolution Pathways of MoS2 Nanosheets in Biological and Environmental Media. AB - Material stability and dissolution in aqueous media are key issues to address in the development of a new nanomaterial intended for technological application. Dissolution phenomena affect biological and environmental persistence; fate, transport, and biokinetics; device and product stability; and toxicity pathways and mechanisms. This article shows that MoS2 nanosheets are thermodynamically and kinetically unstable to O2-oxidation under ambient conditions in a variety of aqueous media. The oxidation is accompanied by nanosheet degradation and release of soluble molybdenum and sulfur species, and generates protons that can colloidally destabilize the remaining sheets. The oxidation kinetics are pH dependent, and a kinetic law is developed for use in biokinetic and environmental fate modeling. MoS2 nanosheets fabricated by chemical exfoliation with n-butyl lithium are a mixture of 1T (primary) and 2H (secondary) phases and oxidize rapidly with a typical half-life of 1-30 days. Ultrasonically exfoliated sheets are in pure 2H phase, and oxidize much more slowly. Cytotoxicity experiments on MoS2 nanosheets and molybdate ion controls reveal the relative roles of the nanosheet and soluble fractions in the biological response. These results indicate that MoS2 nanosheets will not show long-term persistence in living systems and oxic natural waters, with important implications for biomedical applications and environmental risk. PMID- 27267958 TI - [Stress level assessment of the nursing staff in the Intensive Care Unit of a university hospital]. AB - The objective was to determine the work stress level among nursing staff in the Intensive Care Unit of a university hospital and to analyse its relationship with the various sociodemographic and working variables of the studied sample. A study was designed using a quantitative, descriptive and cross-sectional approach. The target population of the study was the nursing staff selected by non-random sampling. The instrument used was the Job Content Questionnaire. Data analysis was performed using SPSS 20. The mean, ranges and standard deviation for each of the variables were calculated. A bivariate analysis was also performed on the social and occupational variables of the sample. The participation rate was 80.90% (N=89). The mean of the Social support dimension was 3.13+/-0.397, for the Psychological demands at work dimension it was 3.10+/-0.384, with a mean of 2.96+/-0.436 being obtained for the Control over the work dimension. In the analysis of sociodemographic and work variables of the sample, only the professional category was significant, with nurses recording higher values in perception of job demands and control over their work compared to nursing assistants. In conclusion, there is a moderate perception of work stress in the analysed group of professionals. Among the sources of stress in the workplace was the low control in decision-making by practitioners, as well as the need to continually learn new things. On the other hand, the support received from colleagues is valued positively by the sample. PMID- 27267959 TI - Laterosporulin10: a novel defensin like Class IId bacteriocin from Brevibacillus sp. strain SKDU10 with inhibitory activity against microbial pathogens. AB - Bacteriocins are antimicrobial peptides (AMPs) produced by bacteria to acquire survival benefits during competitive inter- and intra-species interactions in complex ecosystems. In this study, an AMP-producing soil bacterial strain designated SKDU10 was isolated and identified as a member of the genus Brevibacillus. The AMP produced by strain SKDU10 identified as a class IId bacteriocin with 57.6 % homology to laterosporulin, a defensin-like class IId bacteriocin. However, substantial differences were observed in the antimicrobial activity spectrum of this bacteriocin named laterosporulin10 when compared to laterosporulin. Laterosporulin10 effectively inhibited the growth of Staphylococcus aureus and Mycobacterium tuberculosis (Mtb H37Rv) with LD50 values of 4.0 uM and 0.5 uM, respectively. Furthermore, laterosporulin10 inhibited the growth of Mtb H37Rv strain at about 20 times lower MIC value compared to S. aureus MTCC 1430 or M. smegmatis MC2 155 in vitro and ex vivo. Electron micrographs along with membrane permeabilization studies using FACS analysis revealed that laterosporulin10 is a membrane-permeabilizing peptide. Interestingly, laterosporulin10 was able to efficiently kill Mtb H37Rv strain residing inside the macrophages and did not show haemolysis up to 40 uM concentration. PMID- 27267960 TI - The Buschke-Ollendorff syndrome: a case report of simultaneous osteo-cutaneous malformations in the hand. AB - BACKGROUND: We describe a male with functionally impairing radial deviation of the thumb who presented to us at 24 years of age. Two sclerotic skin lesions had been excised 7 years before because of consecutive skin contracture. Latest radiological examination showed a spotted pattern consistent with osteopoikilosis. CASE PRESENTATION: A corrective osteotomy of the thumb was carried out due to the patients discomfort. Facing the simultaneous osteo cutaneous malformation we postulated a Buschke-Ollendorff syndrome. Buschke Ollendorff syndrome is a rare autosomal-dominant hereditary disorder of connective tissue with typical osteo-cutaneous manifestations. To explore our hypothesis, biopsies were taken from the affected bone lesions and surrounding skin and soft tissue for histological investigation and genetic testing of the LEMD3 gene was performed on blood of the patient. The histology showed typical changes of the bone architecture and a fibrotic collagenous nodule of the skin. The genetic testing on DNA extracted from peripheral blood leucocytes confirmed a heterozygous loss of function mutation in the LEM domain-containing protein 3 (LEMD3) gene coding for the inner nuclear membrane protein MAN1, which causes osteopoikilosis by antagonizing transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signalling. CONCLUSIONS: In atypical cases of simultaneous occurrence of fibrotic skin lesions and a spotted pattern in the X ray we recommend the genetic screening of the LEMD3 gene. A correct diagnosis of Buschke-Ollendorff syndrome is necessary to spare patients from expensive investigations and to provide reassurance about the benign nature of the disease. PMID- 27267961 TI - An observational study of the use of beclomethasone dipropionate suppositories in the treatment of lower urinary tract inflammation in men. AB - BACKGROUND: Nonbacterial prostatitis, together with chronic pelvic pain syndrome, accounts for 90-95 % of prostatitis cases. Anti-inflammatory medications are commonly used to reduce storage/inflammatory symptoms that can deteriorate quality of life. The purpose of this study was to observe the efficacy and safety of beclomethasone dipropionate rectal suppositories (Topster(r)) in inflammations of the lower urinary tract in men. METHODS: Patients underwent diagnostic and therapeutic protocols according to current evidence-based practice. Efficacy assessments: voiding parameters, perineal pain, International Prostate Symptom Score (IPSS), digital rectal examination (DRE). Adverse events and patient compliance were recorded throughout the study. RESULTS: One hundred eighty patients were enrolled, mean age 52 +/- 14.97. Most frequent diagnosis: nonbacterial prostatitis (85 %). All patients completed visits 1 and 2. All patients were treated with beclomethasone dipropionate (BDP) suppositories, 136/180 also with Serenoa repens (SR) extract. Antibiotics were rarely required. 162/180 patients presented clinically significant improvements and terminated treatment. Mean change vs. baseline in voiding frequency: -3.55 +/- 2.70 n/day in patients taking only BDP and -3.68 +/- 2.81 n/day in those taking both BDP and SR (P<.0001 in both groups). Uroflowmetry improved significantly; change from baseline 3.26 +/- 5.35 ml/s in BDP only group and 5.61 +/- 7.32 ml/s in BDP + SR group (P = 0.0002 for BDP, P<.0001 for BDP + SR). Urine stream normal in 35 % of patients at visit 1 and 57.22 % of patients at visit 2. Mean change in perineal pain, on 0-10 VAS, -0.66 +/- 2.24 for BDP only group (P = 0.0699) and -1.37 +/- 2.40 for BDP + SR group (P<.0001). IPSS increased at visit 2. No adverse events were reported. For all parameters, none of the comparisons between groups was found to be statistically significant. CONCLUSION: This study confirmed the drug's good safety profile. We also observed an improvement in the main storage symptoms and clinical findings associated with lower urinary tract inflammation in patients treated with beclomethasone dipropionate suppositories. PMID- 27267962 TI - Prediction of extravasation in pelvic fracture using coagulation biomarkers. AB - PURPOSE: To evaluate the usefulness of coagulation biomarkers, which are easy and quick to analyze in emergency settings, for prediction of arterial extravasation due to pelvic fracture. PATIENTS AND METHODS: The medical records of pelvic fracture patients transferred to the emergency department of Gunma University Hospital between December 2009 and May 2015 were reviewed. Patients were divided into two groups, those with (Extra(+)) and without (Extra(-)) arterial extravasation on enhanced CT or angiography. Levels of fibrin degradation products (FDP), D-dimer, fibrinogen, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, systolic blood pressure, heart rate, the Glasgow Coma Scale, pH, base excess, hemoglobin and lactate levels, the pattern of pelvic injury, and injury severity score were measured at hospital admission, and compared between the two groups. Parameters with a significant difference between the two groups were used to construct receiver operating characteristic (ROC) curves. RESULTS: The study included 29 patients with pelvic fracture. FDP, D dimer, the ratio of FDP to fibrinogen and the ratio of D-dimer to fibrinogen were the most useful parameters for predicting arterial extravasation due to pelvic fracture. FDP, D-dimer, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, and hemoglobin and lactate levels were significantly higher in the Extra(+) group than in the Extra(-) group (FDP, 354.8MUg/mL [median] versus 96.6MUg/mL; D-dimer, 122.3MUg/mL versus 42.1MUg/mL; the ratio of FDP to fibrinogen, 3.39 versus 0.42; the ratio of D-dimer to fibrinogen, 1.14 versus 0.18; hemoglobin, 10.5g/dL versus 13.5g/dL; lactate, 3.5mmol/L versus 1.7mmol/L). The area under the ROC curves for FDP, D-dimer, the ratio of FDP to fibrinogen, the ratio of D-dimer to fibrinogen, hemoglobin and lactate levels were 0.900, 0.882, 0.918, 0.900, 0.815 and 0.765, respectively. CONCLUSION: Coagulation biomarkers, and hemoglobin and lactate levels could be useful to predict the existence of arterial extravasation due to pelvic fracture. The ratio of FDP to fibrinogen and the ratio of D-dimer to fibrinogen were the most accurate markers. Coagulation biomarkers may enable more rapid and specific treatment for pelvic fracture. PMID- 27267963 TI - Recommendations on e-infrastructures for next-generation sequencing. AB - With ever-increasing amounts of data being produced by next-generation sequencing (NGS) experiments, the requirements placed on supporting e-infrastructures have grown. In this work, we provide recommendations based on the collective experiences from participants in the EU COST Action SeqAhead for the tasks of data preprocessing, upstream processing, data delivery, and downstream analysis, as well as long-term storage and archiving. We cover demands on computational and storage resources, networks, software stacks, automation of analysis, education, and also discuss emerging trends in the field. E-infrastructures for NGS require substantial effort to set up and maintain over time, and with sequencing technologies and best practices for data analysis evolving rapidly it is important to prioritize both processing capacity and e-infrastructure flexibility when making strategic decisions to support the data analysis demands of tomorrow. Due to increasingly demanding technical requirements we recommend that e infrastructure development and maintenance be handled by a professional service unit, be it internal or external to the organization, and emphasis should be placed on collaboration between researchers and IT professionals. PMID- 27267964 TI - Computational Insights into the Central Role of Nonbonding Interactions in Modern Covalent Organocatalysis. AB - The flexibility, complexity, and size of contemporary organocatalytic transformations pose interesting and powerful opportunities to computational and experimental chemists alike. In this Account, we disclose our recent computational investigations of three branches of organocatalysis in which nonbonding interactions, such as C-H...O/N interactions, play a crucial role in the organization of transition states, catalysis, and selectivity. We begin with two examples of N-heterocyclic carbene (NHC) catalysis, both collaborations with the Scheidt laboratory at Northwestern. In the first example, we discuss the discovery of an unusual diverging mechanism in a catalytic kinetic resolution of a dynamic racemate that depends on the stereochemistry of the product being formed. Specifically, the major product is formed through a concerted asynchronous [2 + 2] aldol-lactonization, while the minor products come from a stepwise spiro-lactonization pathway. Stereoselectivity and catalysis are the results of electrophilic activation from C-H...O interactions between the catalyst and the substrate and conjugative stabilization of the electrophile. In the second example, we show how knowledge and understanding of the computed transition states led to the development of a more enantioselective NHC catalyst for the butyrolactonization of acyl phosphonates. The identification of mutually exclusive C-H...O interactions in the computed major and minor TSs directly resulted in structural hypotheses that would lead to targeted destabilization of the minor TS, leading to enhanced stereoinduction. Synthesis and evaluation of the newly designed NHC catalyst validated our hypotheses. Next, we discuss two works related to Lewis base catalysis involving 4-dimethylaminopyridine (DMAP) and its derivatives. In the first, we discuss our collaboration with the Smith laboratory at St Andrews, in which we discovered the origins of the regioselectivity in carboxyl transfer reactions. We disclose how different Lewis base catalysts (NHC or DMAP) can lead to different regiomeric products as a result of differing magnitudes of aromatic and C-H...O interactions present in the respective transition states. In the second example, we discuss the mechanism and origins of the stereoselectivity of a reaction catalyzed by a planar-chiral 4 (pyrrolidino)pyridine derivative, namely, the coupling of ketenes with cyanopyrrole. We discovered that the chiral base mechanism is operative, in contrast to the originally proposed Bronsted acid mechanism. The selectivity is determined by the ease with which the major and minor TSs can realize strong stabilizing C-H...N interactions between the pyrrole cyano group and the catalyst. These interactions induce increased catalyst distortion in the minor TS, thereby leading to enantioselectivity. Finally, we discuss our computations related to amine-based organocatalysis in collaboration with the Carter laboratory at Oregon State. We probed the mechanism and stereoselectivity of a bifunctional amine thiourea-catalyzed Michael reaction. Our computations led to the design of an improved catalyst. However, synthesis and tests revealed that this catalyst was prone to degradation to side products that also catalyze the reaction, ultimately reducing the observed enantioselectivity. Lastly, we discuss our study of the mechanism and stereoselectivity of a proline sulfonamide catalyzed Robinson annulation, in which we discovered that the enantioselectivity is controlled by the first Michael step but the diastereoselectivity is controlled by the following Mannich step. PMID- 27267965 TI - Outcomes of a four-year specialist-taught physical education program on physical activity: a cluster randomized controlled trial, the LOOK study. AB - BACKGROUND: The objective of this study was to investigate the effect of a 4-year specialist-taught Physical Education (PE) program on physical activity (PA) among primary school children. METHODS: A 4-year cluster randomised controlled trial was conducted in children (initially aged 8 years) from 29 primary schools (13 Intervention, 16 Control). Intervention students (N = 457) received 2 * 45 min PE lessons per week from specialist-trained PE teachers (68 lessons per year, 272 lessons over 4 years). Control group students (N = 396) received usual practice PE from generalist classroom teachers. PA during PE lessons was examined using the System for Observing Fitness Instruction Time (SOFIT). Pedometers (steps/day) were worn for 7 days each year, and accelerometers were worn concurrently in the final two years to assess moderate to vigorous (MVPA) and sedentary activity. Linear and generalized mixed models were used to determine differences in Intervention and Control student PA and the proportion of students meeting PA guidelines. RESULTS: The intervention increased SOFIT-observed student MVPA during PE lessons by 6.5 mins (16.7 v 10.2, p < 0.001). Within intervention schools, participants increased their whole-day step counts (boys = 449 [CI,140 to 756]; girls = 424 [CI,222 to 626]) and minutes of MVPA (boys = 8.0 [CI,6.8 to 9.2]; girls = 3.5 [CI,1.7 to 5.4]) on PE days. However, compared to the Control group the Intervention did not: increase habitual steps/day or MVPA when averaged over 7 days; elicit greater improvements in these measures over time; or increase the odds of meeting step/day or MVPA recommendations. At age 11 years Intervention group boys were 20 mins less sedentary per day (380 [CI,369 to 391] vs 360 [CI,350 to 369]) and this effect was sustained at age 12 years. CONCLUSIONS: Well-designed specialist-taught PE can improve student PA during PE lessons. However for PE to be a significant contributor to improving habitual PA in pre-adolescent children, daily classes are likely to be required, and even this would need to be supplemented with a wider multicomponent strategy. Our finding of a reduction in sedentary time among Intervention boys warrants further investigation into the potential role PE could play in influencing sedentary behaviour. PMID- 27267966 TI - Five minutes with . . . Scarlett McNally, RCS council member. PMID- 27267967 TI - Retraction Note: Impact of weight loss diet associated with flaxseed on inflammatory markers in men with cardiovascular risk factors: a clinical study. PMID- 27267968 TI - Sodium selenite and cancer related lymphedema: Biological and pharmacological effects. AB - A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex physical therapy. Pharmacotherapy, for example with diuretics, has received little attention, because they were not effective and only offered short term solutions. Sodium selenite showed promise as a cost-effective, nontoxic anti inflammatory agent. Treatment with sodium selenite lowers reactive oxygen species (ROS) production, causes a spontaneous reduction in lymphedema volume, increases the efficacy of physical therapy for lymphedema, and reduces the incidence of erysipelas infections in patients with chronic lymphedema. Besides biological effects in reducing excessive production of ROS, sodium selenite also displays various pharmacological effects. So far the exact mechanisms of these pharmacological effects are mostly unknown, but probably include inhibition of adhesion protein expression. PMID- 27267969 TI - Positive correlation of thyroid hormones and serum copper in children with congenital hypothyroidism. AB - Thyroid hormones are of central relevance for growth and development. However, the underlying molecular mechanisms are still not fully understood. Recent studies in humans and mice have demonstrated that serum levels of selenium (Se) and copper (Cu) are positively affected by thyroid hormones. Given the importance of these trace elements for many biochemical processes, we tested whether this interaction is found in children at risk for hypothyroidism, potentially providing a novel factor contributing to the disturbed development observed in congenital hypothyroidism (CH). We conducted a cross-sectional analysis of 84 children diagnosed with CH displaying a wide range of thyroid hormone concentrations. Serum Se and Cu concentrations were measured by total reflection X-ray fluorescence. Data for thyrotropin (TSH) were available in all, thyroxine (T4) and free thyroxine (fT4) in the majority and triiodothyronine (T3) in 29 of the children. Spearman rank analyzes were performed. Cu and thyroid hormones showed a strong positive correlation (Cu/T4, rho=0.5241, P=0.0003; Cu/T3, rho=0.6003, P=0.0006). Unlike in adults, no associations were found between Se and any of the thyroid hormones. Our data highlight that serum Cu and thyroid hormones are strongly associated already in early postnatal life. Severely hypothyroid children are thus at risk of developing a Cu deficiency if not adequately nourished or supplemented. This finding needs to be verified in larger groups of children in order not to miss an easily-avoidable risk factor for poor development. PMID- 27267970 TI - Innervation from the entorhinal cortex to the dentate gyrus and the vulnerability to Zn2. AB - Hippocampal Zn2+ homeostasis is critical for cognitive activity and hippocampus dependent memory. Extracellular Zn2+ signaling is linked to extracellular glutamate signaling and leads to intracellular Zn2+ signaling, which is involved in cognitive activity. On the other hand, excess intracellular Zn2+ signaling that is induced by excess glutamate signaling is involved in cognitive decline. In the hippocampal formation, the dentate gyrus is the most vulnerable to aging and is thought to contribute to age-related cognitive decline. The layer II of the entorhinal cortex is the most vulnerable to neuronal death in Alzheimer's disease. The perforant pathway provides input from the layer II to the dentate gyrus and is one of the earliest affected pathways in Alzheimer's disease. Medial perforant pathway-dentate granule cell synapses are vulnerable to either excess intracellular Zn2+ or beta-amyloid (Abeta)-bound zinc, which induce transient cognitive decline via attenuation of medial perforant pathway LTP. However, it is unknown whether the vulnerability to excess intracellular Zn2+ is involved in region-specific vulnerability to aging and Alzheimer's disease. To discover a strategy to prevent short-term cognitive decline in normal aging process and the pre-dementia stage of Alzheimer's disease, the present paper deals with vulnerability of medial perforant pathway-dentate granule cell synapses to intracellular Zn2+ dyshomeostasis and its possible involvement in differential vulnerability to aging and Alzheimer's disease in the hippocampal formation. PMID- 27267971 TI - Hydrogel Composites Containing Sacrificial Collapsed Hollow Particles as Dual Action pH-Responsive Biomaterials. AB - In this study hydrogel composites are investigated that contain sacrificial pH responsive collapsed hollow particles (CHPs) entrapped within a poly(acrylamide) (PAAm) network. The CHPs were prepared using a scalable (mainly) water-based method and had a bowl-like morphology that was comparable to that of red blood cells. The CHPs were constructed from poly(methyl methacrylate-co-methacrylic acid), which is a pH-responsive copolymer. The PAAm/CHP composite morphology was probed with optical microscopy, CLSM and SEM. These data showed the CHPs were dispersed throughout the PAAm network. Inclusion of the CHPs within the gel composites increased the modulus in a tunable manner. The CHPs fragmented at pH values greater than the pKa of the particles, and this process decreased the gel modulus to values similar to that of the parent PAAm hydrogel. CHPs containing a model drug were used to demonstrate pH-triggered release from PAAm/CHP and the release kinetics obeyed Fickian diffusion. The composite gels had low cytotoxicity as evidenced by Live/Dead and MTT assays. The hydrogel composites showed dual action pH-triggered softening with simultaneous drug release which occurred without a volume increase. The hydrogel composites may have potential application as enteric gels or for intra-articular drug delivery. PMID- 27267972 TI - Transcriptomics, proteomics and metabolomics driven biomarker discovery in COPD: an update. AB - INTRODUCTION: Diagnosis of chronic obstructive pulmonary disease (COPD), characterized by progressive irreversible airflow limitation, remains a challenge. Lack of sensitive diagnostic markers and alternative treatments have limited patients' survival rate. Herein, we provide for clinicians and scientists a comprehensive review on the various omics platforms used to investigate COPD. AREAS COVERED: This review consists of articles from PubMed (2009-2016) as well as views of the contributing authors. The review highlights the need for COPD biomarker identification and also provides an update on promising candidate markers identified in various biological fluids using omics technologies. Expert commentary: The multi-omics approach holds promise for the development of robust early stage COPD diagnostic markers, screening of high-risk population, and also improved prognosis which could lead to personalized medicine in future. Various factors regulating an omics study including sample size, control selection, disease phenotyping, usage of complementary techniques and result replication in omics-based research are outlined. PMID- 27267974 TI - Running performance in the heat is improved by similar magnitude with pre exercise cold-water immersion and mid-exercise facial water spray. AB - This investigation compared the effects of external pre-cooling and mid-exercise cooling methods on running time trial performance and associated physiological responses. Nine trained male runners completed familiarisation and three randomised 5 km running time trials on a non-motorised treadmill in the heat (33 degrees C). The trials included pre-cooling by cold-water immersion (CWI), mid exercise cooling by intermittent facial water spray (SPRAY), and a control of no cooling (CON). Temperature, cardiorespiratory, muscular activation, and perceptual responses were measured as well as blood concentrations of lactate and prolactin. Performance time was significantly faster with CWI (24.5 +/- 2.8 min; P = 0.01) and SPRAY (24.6 +/- 3.3 min; P = 0.01) compared to CON (25.2 +/- 3.2 min). Both cooling strategies significantly (P < 0.05) reduced forehead temperatures and thermal sensation, and increased muscle activation. Only pre cooling significantly lowered rectal temperature both pre-exercise (by 0.5 +/- 0.3 degrees C; P < 0.01) and throughout exercise, and reduced sweat rate (P < 0.05). Both cooling strategies improved performance by a similar magnitude, and are ergogenic for athletes. The observed physiological changes suggest some involvement of central and psychophysiological mechanisms of performance improvement. PMID- 27267975 TI - Controlling Blinding Trachoma in the Egyptian Delta: Integrating Clinical, Epidemiological and Anthropological Understandings. AB - Trachoma is a leading cause of preventable blindness in the world. The disease is hyperendemic in rural Egypt, where more than 75% of children show signs of having had at least one episode of infectious trachoma during the first year of life. Earlier anthropological and epidemiological observations suggested that trachoma prevalence would decrease if children had their faces washed with soap and water at least once each day. We conducted a community-based intervention to increase face washing in order to control trachoma. In this paper we describe the overall design of this intervention trial and discuss how we integrated anthropological methods and ethnographic data into the design of this successful multi disciplinary, cross-cultural project to prevent trachoma. PMID- 27267973 TI - Characterization of B cells in healthy pregnant women from late pregnancy to post partum: a prospective observational study. AB - BACKGROUND: B cells play a role in pregnancy due to their humoral and regulatory activities. To our knowledge, different maturational stages (from transitional to memory) of circulating B cell subsets have not yet been characterized (cell quantification and phenotype identification) in healthy pregnant women. Thus, the objective of our study was to characterize these subsets (as well as regulatory B cells) from late pregnancy to post-partum and to compare them with the circulating B cells of non-pregnant women. METHODS: In all of the enrolled women, flow cytometry was used to characterize the circulating B cell subsets according to the expression of IgD and CD38 (Bm1-Bm5 classification system). Regulatory B cells were characterized based on the expression of surface antigens (CD24, CD27, and CD38) and the production of IL-10 after lipopolysaccharide stimulation. RESULTS: Compared to the absolute counts of B cells in the non-pregnant women (n = 35), those in the pregnant women (n = 43) were significantly lower (p < 0.05) during the 3rd trimester of pregnancy and on delivery day (immediately after delivery). The percentages of these cells on delivery day and at post-partum were significantly lower than those in the non-pregnant women. In general, the absolute counts and percentages of the majority of the B cell subsets were significantly lower in the 3rd trimester of pregnancy and on delivery day than in the non-pregnant women. However, these counts and percentages did not differ significantly between the post-partum and the non-pregnant women. The most notable exceptions to the above were the percentages of naive B cells (which were significantly higher in the 3rd trimester and on delivery day than in the non pregnant women) and of CD24(hi)CD38(hi) regulatory B cells (which were significantly higher in the post-partum than in the non-pregnant women). CONCLUSION: According to our study, the peripheral B cell compartment undergoes quantitative changes during normal late pregnancy and post-partum. Such findings may allow us to better understand immunomodulation during human pregnancy and provide evidence that could aid in the development of new strategies to diagnose and treat pregnancy-associated disturbances. Our findings could also be useful for studies of the mechanisms of maternal responses to vaccination and infection. PMID- 27267976 TI - Causation as Strategy: Interpreting Humours among Tibetan Refugees. AB - The article focuses on the incidence of humoural wind ( rlung ) disorders among Tibetan exiles in India. It investigates the reasons behind the emergence of rlung as a significant problem among Tibetan exiles, and seeks to unpack some of the local meanings of this 'epidemic'. Previous studies have generally described rlung disorders as symptomatic of political and moral concerns, highlighting the connections that Tibetans make between physical, moral and psychological states in the context of Buddhist practice and everyday life. This paper aims to further nuance these findings by showing that, while Tibetan exiles include complex causes linked to morality and psychosocial wellbeing in their explanations of rlung disorders, they also 'cut' into this explanatory network in strategic ways, sometimes bypassing religious or psychosocial interpretations of illness altogether. Drawing on this analysis, the article warns researchers against literal readings of general religious precepts when analysing people's everyday negotiations of illness and wellbeing: the attribution of causation is always strategic, and religious observance should never be assumed to be uniform, or taken as a given. PMID- 27267977 TI - Myths, Fallacies and Misconceptions: Applying Social Marketing for Promoting Appropriate Health Seeking Behavior in Pakistan. AB - Myths and fallacies have existed ever since societies began, influencing the perceptions about health, and the cause and cure of health related problems. The role of such myths in governing the health and health seeking behavior of people is quite explicit. Misconceptions about breast-feeding, pre-lacteal feed, weaning, dietary habits and other health related matters are commonly heard in the cultures of developing countries. False perceptions have undoubtedly an impact on the health seeking behavior. People coming from the low socio-economic strata in rural areas suffer the most. They lack access to formal health care services and are unable to afford specialized medical care. This gives rise to alternative health seeking behaviors. A considerable majority of people prefer to go to spiritual healers, quacks and other non-formal health providers for the treatment of their ailments. This paper has reviewed a variety of myths, fallacies and misconceptions collectively in the cultural context and has attempted to relate them to the health seeking behaviors of Pakistani people. The paper is based on the contemporary literature review and library work, focusing on finding the feasible strategies to address a variety of myths and misconceptions. Since myths have many adverse implications on the health of the people, an effective way of motivating low income and high risk people to adopt healthy behavior is 'social marketing'. Creating 'health promotion committees' at village level sounds like another doable strategy to ameliorate the situation in order to educate people to take care of not only their own health but of the future generations as well. PMID- 27267978 TI - 'Do as I say, not as I do': Medical Education and Foucault's Normalizing Technologies of Self. AB - Medical training as a process of professional socialization has been well explored within the fields of medical education, medical sociology and medical anthropology. Our contribution is to outline a bio-power, more specifically an anatomo-politics, of medical education. The current research aimed to explore perspectives on what is commonly termed the 'hidden curriculum'. We conducted interviews with pre-clinical medical students, clinical teachers and medical educators within a New Zealand medical school. In this paper, we outline ways that respondents described the juxtaposition of the undeclared or hidden aspects of medical education with the formal declared curriculum. Our respondents were aware of incongruencies across these components that resulted in mixed messages to students. Curricula initiatives aim to encourage new forms of subjectivity so that students are often expected to be the kinds of doctors that their teachers are not. However, the success of such initiatives is dependent on the degree of alignment between informal and formal components of the curriculum. PMID- 27267979 TI - Nurturing Women and the BRCA Genes: Gender, Activism and the Paradox of Health Awareness. AB - This paper explores the relationship between breast cancer activism and a newly emergent arena of 'predictive' medicine, breast cancer genetics. Drawing on ethnographic research in UK cancer genetic clinics, it explores the way the goals and gendered values of a certain kind of breast cancer activism operate at the interface between patients and practitioners. It examines how the morality of health awareness and the value female nurturance are implicated in and configured by clinical encounters. Outlining the dense and dynamic 'traffic' around the work of transmission, the paper examines how the same gendered values that may enable this field of practice can also result in uneasy consequences for patients, their kin, as well as practitioners. Exploring these intersections demonstrates the scope and challenges for knowledge and care, as well as the paradoxical value of health awareness in an emerging field of genetic medicine. PMID- 27267980 TI - Ambivalence and Anxiety in the Psychiatric Systems of the United States and Japan. AB - Obsessive-compulsive disorder and the Japanese condition known as taijin kyofusho are classified as 'anxiety disorders' by US and Japanese psychiatrists. While members of the biomedical community might prefer to see this as evidence of a human universal, the similarity between the two is not primarily biological, but cultural and developmental. Both disorders develop out of a conflict between or within cultural significant values, values that refer to and develop from the dynamics of emotional attachment. PMID- 27267981 TI - Reviews. PMID- 27267982 TI - Animals, anoxic environments, and reasons to go deep. AB - One of the classic questions in the early evolution of eukaryotic life concerns the role of oxygen. Many unicellular eukaryotes are strict anaerobes and many animals have long anoxic phases in their life cycle. But are there also animals that can complete their life cycle without oxygen? In an ongoing debate in BMC Biology, Danovaro and colleagues say "yes" while Bernhard and colleagues say "no". The debate concerns reports of anoxic metazoans in deep sea anaerobic habitats. PMID- 27267983 TI - Changing the Antibiotic Prescribing of general practice registrars: the ChAP study protocol for a prospective controlled study of a multimodal educational intervention. AB - BACKGROUND: Australian General Practitioners (GPs) are generous prescribers of antibiotics, prompting concerns including increasing antimicrobial resistance in the community. Recent data show that GPs in vocational training have prescribing patterns comparable with the high prescribing rate of their established GP supervisors. Evidence-based guidelines consistently advise that antibiotics are not indicated for uncomplicated upper respiratory tract infections (URTI) and are rarely indicated for acute bronchitis. A number of interventions have been trialled to promote rational antibiotic prescribing by established GPs (with variable effectiveness), but the impact of such interventions in a training setting is unclear. We hypothesise that intervening while early-career GPs are still developing their practice patterns and prescribing habits will result in better adherence to evidence-based guidelines as manifested by lower antibiotic prescribing rates for URTIs and acute bronchitis. METHODS/DESIGN: The intervention consists of two online modules, a face-to-face workshop for GP trainees, a face-to-face workshop for their supervisors and encouragement for the trainee-supervisor dyad to include a case-based discussion of evidence-based antibiotic prescribing in their weekly one-on-one teaching meetings. We will use a non-randomised, non-equivalent control group design to assess the impact on antibiotic prescribing for acute upper respiratory infections and acute bronchitis by GP trainees in vocational training. DISCUSSION: Early-career GPs who are still developing their clinical practice and prescribing habits are an underutilized target-group for interventions to curb the growth of antimicrobial resistance in the community. Interventions that are embedded into existing training programs or are linked to continuing professional development have potential to increase the impact of existing interventions at limited additional cost. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12614001209684 (registered 17/11/2014). PMID- 27267984 TI - The association of Red cell distribution width and in-hospital mortality in older adults admitted to the emergency department. AB - BACKGROUND: The objective of the study was to test the hypothesis that elevated red cell distribution width (RDW) at admission increases the risk of mortality in older patients admitted to the emergency department (ED). METHODS: We performed a retrospective analysis of patients admitted to the ED between May 2013 and October 2013. We included patients who were older than 65 years who visited the ED with any medical problems. Baseline RDW values were measured at the time of admission to the ED. The primary outcome was all-cause in-hospital mortality. Multivariate logistic analysis was performed. RESULTS: A total of 1,990 patients were finally included in this study. The mean age was 75 years (SD 7), and 936 (47 %) subjects were male. The in-hospital mortality rate was 3.76 % (74 patients). RDW values higher in non-survivors than in survivors (15.9 +/- 2.5 vs. 13.8 +/- 1.7, p < 0.001). Multivariate logistic analysis showed that RDW was associated with all-cause in-hospital mortality after adjusting for other confounding factors. DISCUSSION: RDW value at admission is an independent predictor of all-cause in-hospital mortality among patients older than 65 years. After adjustment for multiple confounders, the all-cause in-hospital mortality rate increased by 21.8% for each 1% increase in RDW. CONCLUSION: These results show that RDW at admission is associated with in-hospital mortality among patients older than 65. Thus, RDW at admission may represent a surrogate marker of disease severity. We caution against using these findings to aid clinical decision-making process until they are externally validated. PMID- 27267985 TI - Lanthanide-Potassium Biphenyl-3,3'-disulfonyl-4,4'-dicarboxylate Frameworks: Gas Sorption, Proton Conductivity, and Luminescent Sensing of Metal Ions. AB - A novel sulfonate-carboxylate ligand of biphenyl-3,3'-disulfonyl-4,4' dicarboxylic acid (H4-BPDSDC) and its lanthanide-organic frameworks {[LnK(BPDSDC)(DMF)(H2O)].x(solvent)}n (JXNU-2, where JXNU denotes Jiangxi Normal University, DMF indicates dimethylformamide, and Ln = Sm(3+), Eu(3+), and Pr(3+)) were synthesized and structurally characterized. The three isomorphous lanthanide compounds feature three-dimensional frameworks constructed from one-dimensional (1D) rod-shaped heterometallic Ln-K secondary building units and are an illustration of a Kagome-like lattice with large 1D hexagonal channels and small 1D trigonal channels. The porous material of the representive JXNU-2(Sm) has an affinity to quadrupolar molecules such as CO2 and C2H2. In addition, the JXNU 2(Sm) compound exhibits humidity- and temperature-dependent proton conductivity with a large value of 1.11 * 10(-3) S cm(-1) at 80 degrees C and 98% relative humidity. The hydrophilic sulfonate group on the surface of channels facilitates enrichment of the solvate water molecules in the channels, which enhances the proton conductivity of this material. Moreover, the JXNU-2(Eu) material with the characteristic bright red color shows the potential for recognition of K(+) and Fe(3+) ions. The enhancing Eu(3+) luminescence with the K(+) ion and quenching Eu(3+) luminescence with the Fe(3+) ion can be associated with the functional groups of the organic ligand. PMID- 27267986 TI - Validity of clinically significant change classifications yielded by Jacobson Truax and Hageman-Arrindell methods. AB - BACKGROUND: Reporting of the clinical significance of observed changes is recommended when publishing mental health treatment outcome studies and is increasingly used in routine outcomes monitoring systems. Since recovery rates vary with the method chosen, we investigated the validity of classifications of clinically significant change when the Jacobson-Truax method and the Hageman Arrindell method were used. METHODS: Of 718 inpatients who completed the Depression Anxiety Stress Scales (DASS-21) and Quality of Life Enjoyment and Satisfaction Questionnaire at admission and discharge to a psychiatric clinic, 355 were invited (and 119 agreed) to complete the questionnaires and the Recovery Assessment Scale six weeks post discharge. RESULTS: Both the JT and HA methods showed comparably good validity when referenced against the other indices. Clinically significant change on the DASS-21 was related to a greater consumer based sense of recovery, greater perceived quality of life, and fewer readmissions to hospital within 28 days of discharge. CONCLUSIONS: Since there was found to be no advantage to using one method over another when recovery is of interest, the simpler JT method is recommended for routine usage. PMID- 27267987 TI - The impact of manganese on biofilm development of Bacillus subtilis. AB - Bacterial biofilms are dynamic and structurally complex communities, involving cell-to-cell interactions. In recent years, various environmental signals that induce the complex biofilm development of the Gram-positive bacterium Bacillus subtilis have been identified. These signalling molecules are often media components or molecules produced by the cells themselves, as well as those of other interacting species. The responses can also be due to depletion of certain molecules in the vicinity of the cells. Extracellular manganese (Mn2+) is essential for proper biofilm development of B. subtilis. Mn2+ is also a component of practically all laboratory biofilm-promoting media used for B. subtilis. Comparison of complex colony biofilms in the presence or absence of supplemented Mn2+ using microarray analyses revealed that genes involved in biofilm formation are indeed downregulated in the absence of Mn2+. In addition, Mn2+ also affects the transcription of several other genes involved in distinct differentiation pathways of various cellular processes. The effects of Mn2+ on other biofilm related traits like motility, antimicrobial production, stress and sporulation were followed using fluorescent reporter strains. The global transcriptome and morphology studies highlight the importance of Mn2+ during biofilm development and provide an overview on the expressional changes in colony biofilms in B. subtilis. PMID- 27267988 TI - Biochemical recurrence-free survival and pathological outcomes after radical prostatectomy for high-risk prostate cancer. AB - BACKGROUND: We propose to improve the prognostic assessment after radical prostatectomy (RP) by dividing high-risk prostate cancer (hrPCa) (according to the d'Amico classification) into subgroups combining 1, 2 or 3 criteria of aggressiveness (cT2c-T3a, PSA >20 ng/ml, Gleason score (GS) > 7). METHODS: Data from 4795 hrPCa patients who underwent RP in two French university hospitals from 1991 to 2013 were analyzed. Subgroups were formed to determine whether an increasing number (1, 2 or 3) of criteria of tumor aggressiveness was associated with poorer oncological results and early biochemical recurrence (BCR) (PSA > 0.2 ng/ml). These results were compared using Fisher's exact test and BCR was compared according to the Kaplan-Meier method. RESULTS: Eight hundred fifteen patients were treated by RP for hrPCa (8 %). Four hundred eleven patients (79.5 %) presented 1 RF (Risk Factor), 93 (18.0 %) 2 RF and 13 (2.5 %) 3 RF. Lymph node invasion and positive margin rates were 12.4 and 44.1 %, respectively. The prognostic sub-stratification based on these 3 factors was significantly predictive for adverse pathologic features and for oncologic outcomes. BCR free survival was respectively 56.4, 27.06 and 18.46 % for 1RF, 2RF and 3RF (p < 0.0001). However, no predominant negative criterion was found. CONCLUSION: Oncologic results after RP are heterogenous within the hrPCa risk group. Sub stratification based on three well-defined criteria leads to a better identification of the most aggressive cancers. On the other hand, RP provides both effective cancer control and satisfactory survival rates in patients with only one risk factor. PMID- 27267989 TI - Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B. AB - Serum cystatin C (Cys C) has a number of advantages over serum creatinine in the evaluation of kidney function. Apart from Cys C level itself, several formulas have also been introduced in different clinical settings for the estimation of glomerular filtration rate (GFR) based upon serum Cys C level. The aim of the present study was to compare a serum Cys C-based equation with Cockcroft-Gault serum creatinine-based formula, both used in the calculation of GFR, in patients receiving amphotericin B. Fifty four adult patients with no history of acute or chronic kidney injury having been planned to receive conventional amphotericin B for an anticipated duration of at least 1 week for any indication were recruited. At three time points during amphotericin B treatment, including days 0, 7, and 14, serum cystatin C as well as creatinine levels were measured. GFR at the above time points was estimated by both creatinine (Cockcroft-Gault) and serum Cys C based equations. There was significant correlation between creatinine-based and Cys C-based GFR values at days 0 (R = 0.606, P = 0.001) and 7 (R = 0.714, P < 0.001). In contrast to GFR estimated by the Cockcroft-Gault equation, the mean (95 % confidence interval) Cys C-based GFR values at different studied time points were comparable within as well as between patients with and without amphotericin B nephrotoxicity. Our results suggested that the Gentian Cys C-based GFR equation correlated significantly with the Cockcroft-Gault formula at least at the early time period of treatment with amphotericin B. Graphical abstract Comparison between a serum creatinine-and a cystatin C-based glomerular filtration rate equation in patients receiving amphotericin B. PMID- 27267990 TI - A critical appraisal of continence in bladder exstrophy: Long-term outcomes of the complete primary repair. AB - INTRODUCTION: Long-term continence outcomes for patients with bladder exstrophy are lacking in the literature. The complete primary repair of exstrophy (CPRE) is a widely adopted approach that seeks to normalize anatomy at the initial repair, thereby allowing early bladder filling and cycling. Previous reports of continence following CPRE, however, are limited by variable follow-up duration and continence definitions. OBJECTIVE: To assess continence and factors associated with a positive outcome in a cohort of patients following CPRE with long-term follow-up. STUDY DESIGN: A retrospective chart review was conducted of all patients with primary bladder closure using CPRE at the present institution for classic bladder exstrophy from 1990 to 2010. Patients <6 years of age or with an incomplete continence assessment at last follow-up were excluded. Continence was defined as voiding volitionally with dry intervals of >=3 h, which was consistent with other high-volume series in the literature. RESULTS: Twenty-nine of the 52 patients (56%) were eligible for inclusion. Twelve patients were continent at last follow-up, including seven boys and five girls. Mean follow-up for the entire cohort was 148 months. The Summary table displays comparisons between continent and incontinent patients. Of patients achieving continence, 42% did not require further continence operations, while 17% required only one additional continence operation. DISCUSSION: Long-term CPRE continence rates were lower than previously reported, but comparable to other series in the literature. Of those achieving continence, 59% will do so with zero or one additional operation. Sex and osteotomy status were not associated with continence outcomes, although age at follow-up was a predictor of continence, favoring older patients in the present series. The study was limited by lack of standardized, patient reported continence outcomes and by the retrospective nature of the review. However, the data add to the literature of long-term continence outcomes and are important for counseling families both at initial repair and follow-up. CONCLUSIONS: Complete primary repair of exstrophy can achieve continence without additional operations in a subset of patients. Some patients, however, may not achieve continence until adolescence, underscoring the need for long-term urologic follow-up in patients with bladder exstrophy. PMID- 27267991 TI - Urethral duplication in girls: Three cases associating an accessory epispadiac urethra and a main hypospadiac urethra. AB - INTRODUCTION: Urethral duplication is extremely rare in girls, with less than 40 cases reported so far. Most of them present as a prepubic sinus. Literature is scare regarding aetiology, classification and management in other forms. This study presents three cases of sagittal urethral duplication in girls presenting a main hypospadiac urethra and an accessory epispadiac urethra. PATIENTS AND METHODS: Medical records were retrospectively reviewed of three girls with urethral duplication managed over a 30-year period at a single institution. Circumstances of diagnosis, management and outcomes were analysed. RESULTS: The oldest case presented as a neonatal retrovesical mass with an accessory clitoral stream, whereas the two more recent cases presented with antenatal hydrocolpos and bilateral ureterohydronephrosis. Cases 1 and 3 had an incomplete duplication, while Case 2 had a complete form. In Case 3, the duplication was associated with a urogenital sinus and an anteriorly placed anus. Management involved resection of the epispadiac accessory urethra to achieve continence, with dilatation and/or mobilisation of the hypospadiac one. All girls are now aged >5 years old and are continent, and one is old enough to have normal menstruation. Renal function is normal in all. The summary table presents the schematic anatomical description as shown on micturating cystourethrogram and endoscopy, as well as the management for each patient. DISCUSSION: Step-by-step management is necessary in urethral duplication. The neonatal emergency is to release the urinary tract compression by evacuating urinary retention or hydrocolpos. Later in infancy, decision has to be taken regarding the urethras. If the resection of the epispadiac accessory urethra seems acceptable to achieve continence, the attitude towards the hypospadiac channel is more controversial and should be individualised. Embryologic and aetiopathogenic pathways are still missing to uniformly characterise the malformation. CONCLUSION: Paediatric urologists should remember that there is a wide spectrum of urethral duplication in girls, and that various presentations exist beside the more classic prepubic sinus. PMID- 27267992 TI - Altitude as a risk factor for the development of hypospadias. Geographical cluster distribution analysis in South America. AB - OBJECTIVE: Hypospadias is the most common congenital anomaly affecting the genitals. It has been established as a multifactorial disease with increasing prevalence. Many risk factors have been identified such as prematurity, birth weight, mother's age, and exposure to endocrine disruptors. In recent decades multiple authors using surveillance systems have described an increase in prevalence of hypospadias, but most of the published literature comes from developed countries in Europe and North America and few of the published studies have involved cluster analysis. Few large-scale studies have been performed addressing the effect of altitude and other geographical aspects on the development of hypospadias. Acknowledging this limitation, we present novel results of a multinational spatial scan statistical analysis over a 30-year period in South America and an altitude analysis of hypospadias distribution on a continent level. METHOD: A retrospective review was performed of the Latin American collaborative study of congenital malformations (ECLAMC). A total of 4,020,384 newborns was surveyed between 1982 and December 2011 in all participating centers. We selected all patients with hypospadias. All degrees of clinical severity were included in the analysis. Each participating center was geographically identified with its coordinates and altitude above sea level. A spatial scan statistical analysis was performed using Kulldorf's methodology and a prevalence trend analysis over time in centers below and above 2000 m. RESULTS: During the study period we found 159 hospitals in six different countries (Colombia, Bolivia, Brazil, Argentina, Chile, and Uruguay) with 4,537 cases of hypospadias and a global prevalence rate of 11.3/10,000 newborns. Trend analysis showed that centers below 2000 m had an increasing trend with an average of 10/10,000 newborns as opposed to those centers above 2000 m that showed a reducing trend with an average prevalence of 7.8 (p = 0.1246). We identified clusters with significant increases of prevalence in five centers along the coast at an average altitude of 219.8 m above sea level (p > 0.0000). Reduction in prevalence was found in clusters located in two centers on the Andes mountains. Altitude of 2,000 m was associated with hypospadias (Figure), with an OR 0.59 (0.5-0.69). There are ethnic arguments to support our results supported by protective polymorphism distribution in high lands. CONCLUSION: Altitude above 2,000 m is suggested to have a protective effect for hypospadias. Specific clusters have been identified with increased risk for hypospadias. Environmental risk factors in these areas need to be further studied given the association seen between altitude and the distribution of more severe cases. PMID- 27267994 TI - [Dyslipidemia in patients with rheumatoid arthritis]. PMID- 27267993 TI - Surgical and molecular pathology of pancreatic neoplasms. AB - BACKGROUND: Histologic characteristics have proven to be very useful for classifying different types of tumors of the pancreas. As a result, the major tumor types in the pancreas have long been classified based on their microscopic appearance. MAIN BODY: Recent advances in whole exome sequencing, gene expression profiling, and knowledge of tumorigenic pathways have deepened our understanding of the underlying biology of pancreatic neoplasia. These advances have not only confirmed the traditional histologic classification system, but also opened new doors to early diagnosis and targeted treatment. CONCLUSION: This review discusses the histopathology, genetic and epigenetic alterations and potential treatment targets of the five major malignant pancreatic tumors - pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, acinar cell carcinoma and pancreatoblastoma. PMID- 27267995 TI - The His131Arg substitution in the FCGR2A gene (rs1801274) is not associated with the severity of influenza A(H1N1)pdm09 infection. AB - BACKGROUND: The virulence and pathogenicity of different influenza strains are responsible for a more or less severe disease. Recent studies have attempted to understand how host genetic factors may influence the clinical presentation of the disease. In the present study, the His131Arg (rs1801274) polymorphism was investigated in individuals from a Brazilian admixed population with a diagnosis of influenza A(H1N1)pdm09 infection. METHODS: In the present study, the influence of the His131Arg (rs1801274) polymorphism, a variant of the FCGR2A gene, was investigated in 436 patients with a diagnosis of influenza A(H1N1)pdm09, evaluated at health services in the northern and northeastern regions of Brazil between June 2009 and August 2010. Patients were divided into a group of non hospitalized patients (n = 192) and a group of hospitalized patients (n = 244; 100 of them died). RESULTS: No significant difference in the allele or genotype frequencies of the rs1801274 polymorphism was observed between groups (p = 0.952 and p = 0.388). Multinomial logistic regression showed no effect of the rs1801274 polymorphism on severity or death of patients from the Brazilian admixed population (p = 0.368 and p = 0.469). CONCLUSIONS: The rs1801274 polymorphism is not associated with severe disease in patients infected with influenza A(H1N1)pdm09. PMID- 27267996 TI - Fabrication and evaluation of nanoparticle-assembled BSA microparticles for enhanced liver delivery of glycyrrhetinic acid. AB - The aim of the present study was to prepare and evaluate microparticle formulation encapsulated with glycyrrhetinic acid (GA) based on bovine serum albumin (BSA). The drug-loaded nanoparticles were firstly formed by a simple desolvation method, and were further assembled into microparticles using zinc chloride and glutaraldehyde as crosslinkers. The obtained microparticles contained approximately 30% (w/w) drug and showed as spherical particles with a size of about 2 MUm. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that GA lost its crystallinity during the nano/microencapsulation process. In vitro dissolution study demonstrated a typical sustained-release pattern for 24 h with a burst of 28.1% at the first 30 min, which fitted well by Higuchi model. After intravenous administration into mice, the microparticle formulation remained a higher drug level than the solution formulation in blood and liver for more than 18 h. These results suggested the potential benefit of using the prepared albumin microparticles as a promising vector for enhanced liver delivery of poorly water-soluble drug. PMID- 27267997 TI - Carnosic acid promotes degradation of the androgen receptor and is regulated by the unfolded protein response pathway in vitro and in vivo. AB - Androgen deprivation therapy in prostate cancer is extremely effective; however, due to the continuous expression and/or mutagenesis of androgen receptor (AR), the resistance to antihormonal therapy is a natural progression. Consequently, targeting the AR for degradation offers an alternate approach to overcome this resistance in prostate cancer. In this study, we demonstrate that carnosic acid, a benzenediol diterpene, binds the ligand-binding domain of the AR and degrades the AR via endoplasmic reticulum (ER) stress-mediated proteasomal degradative pathway. In vitro, carnosic acid treatment induced degradation of AR and decreased expression of prostate-specific antigen in human prostate cancer cell lines LNCaP and 22Rv1. Carnosic acid also promoted the expression of ER proteins including BiP and CHOP in a dose-dependent manner. Downregulation of CHOP by small interfering RNA somewhat restored expression of AR suggesting that AR degradation is dependent on ER stress pathway. Future studies will need to evaluate other aspects of the unfolded protein response pathway to characterize the regulation of AR degradation. Furthermore, cotreating cells individually with carnosic acid and proteasome inhibitor (MG-132) and carnosic acid and an ER stress modulator (salubrinal) restored protein levels of AR, suggesting that AR degradation is mediated by ER stress-dependent proteasomal degradation pathway. Degradation of AR and induction of CHOP protein were also evident in vivo along with a 53% reduction in growth of xenograft prostate cancer tumors. In addition, carnosic acid-induced ER stress in prostate cancer cells but not in normal prostate epithelial cells procured from patient biopsies. In conclusion, these data suggest that molecules such as carnosic acid could be further evaluated and optimized as a potential therapeutic alternative to target AR in prostate cancer. PMID- 27267998 TI - Hypermutation and unique mutational signatures of occupational cholangiocarcinoma in printing workers exposed to haloalkanes. AB - Cholangiocarcinoma is a relatively rare cancer, but its incidence is increasing worldwide. Although several risk factors have been suggested, the etiology and pathogenesis of the majority of cholangiocarcinomas remain unclear. Recently, a high incidence of early-onset cholangiocarcinoma was reported among the workers of a printing company in Osaka, Japan. These workers underwent high exposure to organic solvents, mainly haloalkanes such as 1,2-dichloropropane (1,2-DCP) and/or dichloromethane. We performed whole-exome analysis on four cases of cholangiocarcinoma among the printing workers. An average of 44.8 somatic mutations was detected per Mb in the genome of the printing workers' cholangiocarcinoma tissues, approximately 30-fold higher than that found in control common cholangiocarcinoma tissues. Furthermore, C:G-to-T:A transitions with substantial strand bias as well as unique trinucleotide mutational changes of GpCpY to GpTpY and NpCpY to NpTpY or NpApY were predominant in all of the printing workers' cholangiocarcinoma genomes. These results were consistent with the epidemiological observation that they had been exposed to high concentrations of chemical compounds. Whole-genome analysis of Salmonella typhimurium strain TA100 exposed to 1,2-DCP revealed a partial recapitulation of the mutational signature in the printing workers' cholangiocarcinoma. Although our results provide mutational signatures unique to occupational cholangiocarcinoma, the underlying mechanisms of the disease should be further investigated by using appropriate model systems and by comparison with genomic data from other cancers. PMID- 27268000 TI - HCV knowledge among a sample of HCV positive Aboriginal Australians residing in New South Wales. AB - Australian Aboriginal and Torres Strait Islanders are overrepresented in both the prevalence and incidence of the hepatitis C (HCV). HCV knowledge has been associated with a range of positive health behaviours. HCV knowledge has previously been investigated as a single construct; however examining different knowledge domains (i.e. transmission, risk of complications, testing and treatment) separately may be beneficial. This study investigated whether having greater HCV knowledge in different domains is associated with self-reported positive health behaviours. 203 Aboriginal people living with HCV completed a survey assessing HCV knowledge, testing and care, lifestyle changes since diagnosis and treatment intent. Respondents' knowledge was relatively high. Greater knowledge of risk of health complications was associated with undertaking more positive lifestyle changes since diagnosis. Respondents testing and treatment knowledge was significantly associated with incarceration, lifestyle changes since diagnosis and future treatment intentions. This study illustrates the importance of ensuring that knowledge is high across different HCV domains to optimise a range of positive health behaviours of Aboriginal people living with HCV. Future health promotion campaigns targeted at Aboriginal people living with HCV could benefit from broadening their focus from prevention to other domains such as testing and treatment. PMID- 27268001 TI - Could targeting disease specific fear and anxiety improve COPD outcomes? PMID- 27267999 TI - An exome-wide analysis of low frequency and rare variants in relation to risk of breast cancer in African American Women: the AMBER Consortium. AB - A large percentage of breast cancer heritability remains unaccounted for, and most of the known susceptibility loci have been established in European and Asian populations. Rare variants may contribute to the unexplained heritability of this disease, including in women of African ancestry (AA). We conducted an exome-wide analysis of rare variants in relation to risk of overall and subtype-specific breast cancer in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, which includes data from four large studies of AA women. Genotyping on the Illumina Human Exome Beadchip yielded data for 170 812 SNPs and 8287 subjects: 3629 cases (1093 estrogen receptor negative (ER-), 1968 ER+, 568 ER unknown) and 4658 controls, the largest exome chip study to date for AA breast cancer. Pooled gene-based association analyses were performed using the unified optimal sequence kernel association test (SKAT-O) for variants with minor allele frequency (MAF) <= 5%. In addition, each variant with MAF >0.5% was tested for association using logistic regression. There were no significant associations with overall breast cancer. However, a novel gene, FBXL22 (P = 8.2*10(-6)), and a gene previously identified in GWAS of European ancestry populations, PDE4D (P = 1.2*10(-6)), were significantly associated with ER- breast cancer after correction for multiple testing. Cases with the associated rare variants were also negative for progesterone and human epidermal growth factor receptors-thus, triple-negative cancer. Replication is required to confirm these gene-level associations, which are based on very small counts at extremely rare SNPs. PMID- 27268002 TI - A link between asthenia, pallor, and jaundice. PMID- 27268003 TI - Prenatal, birth and early life predictors of sedentary behavior in young people: a systematic review. AB - BACKGROUND: Our aim was to systematically summarize the evidence on whether prenatal, birth and early life factors up to 6 years of age predict sedentary behavior in young people (<=18 years). METHODS: PRISMA guidelines were followed, and searches were conducted in PubMed, SPORTDiscus, EMBASE and Web of Science up to December 1, 2015. We included observational (non-intervention) and longitudinal studies, that reported data on the association between one or more of the potential predictors and objectively or subjectively measured sedentary behavior. Study quality was assessed using a formal checklist and data extraction was performed using standardized forms independently by two researchers. RESULTS: More than 18,000 articles were screened, and 16 studies, examining 10 different predictors, were included. Study quality was variable (0.36-0.95). Two studies suggest that heritability and BMI in children aged 2-6 years were significant predictors of sedentary behavior later in life, while four and seven studies suggest no evidence for an association between gestational age, birth weight and sedentary behavior respectively. There was insufficient evidence whether other prenatal, birth and early life factors act as predictors of later sedentary behavior in young people. CONCLUSION: The results suggest that heritability and early childhood BMI may predict sedentary behavior in young people. However, small number of studies included and methodological limitations, including subjective and poorly validated sedentary behavior assessment, limits the conclusions. TRIAL REGISTRATION: The systematic review is registered in the International Prospective Register of Systematic Reviews, PROSPERO, 17.10.2014 ( CRD42014014156 ). PMID- 27268004 TI - A cross-sectional study on nutrient intake and -status in inflammatory bowel disease patients. AB - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) can be associated with nutritional problems. The aim of this study was to investigate diet and nutritional status of IBD patients. METHODS: A total of 78 participants (35 men and 43 women aged 18-74 years) were included in this cross-sectional study. The majority (80 %) of the participant received infliximab treatment. Participants filled out disease related questionnaires and 31 participants also a 3-day food record. Body composition was measured and blood samples analysed in order to estimate nutritional status. RESULTS: The majority (87 %) claimed that diet affects digestive tract symptoms and 72 % had changed diet accordingly. The most common foods restricted were dairy products (60 %), processed meat (55 %), soft drinks (46 %), alcohol (45 %) and fast food (44 %). Body mass index was mostly in the overweight range but 46 % of the participants had been diagnosed with some nutritional deficiency since IBD diagnosis (most common was iron deficiency: 39 %). Patients who restricted meat products had lower ferritin values (48 +/- 39 vs. 95 +/- 74 MUg/L, P = 0.011). Intake of vitamin D and calcium were not adequate (65 % below recommeded intake for both) and 60 % had poor vitamin D status. CONCLUSION: IBD patients often change their dietary intake in order to affect digestive tract symptoms. Many patients have a history of nutrient deficiency. Restriction of dairy and meat consumption is common and is negatively associated with intake or status of micronutrients like calcium and iron. Dietary advice by a dietitian and use of potentially helpful dietary supplements is indicated. PMID- 27268005 TI - Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) presenting as major depression. AB - BACKGROUND: Hashimoto's encephalopathy is a neuropsychiatric disease with symptoms of cognitive impairment, stroke-like episodes, seizures, and psychotic or affective symptoms associated with autoimmune thyroiditis and excellent steroid responsiveness; therefore, it is also called "steroid responsive encephalopathy associated with autoimmune thyroiditis" (SREAT). CASE PRESENTATION: We present the case of a 50-year-old woman who developed a first onset depressive syndrome with predominant cognitive impairment and inability to work. Antidepressive treatment and cognitive behavioral therapy over two years were unsuccessful. Neurological examination was unremarkable. Serum analysis showed increased thyroid peroxidase and thyroglobulin antibodies. Cerebrospinal fluid protein and albumin quotient were increased. Magnetic resonance imaging depicted unspecific, supratentorial white matter lesions and frontal accentuated brain atrophy. Electroencephalography was normal. Neuropsychological testing for attentional performance was below average. High-dose intravenous treatment with methylprednisolone over 5 days and oral dose reduction over 3 weeks led to the sustained improvement of clinical symptoms. Following discharge from the hospital, the patient returned to work, and 6.5 months after the start of therapy, no neuropsychological deficit remained. CONCLUSION: This case report illustrates that SREAT might present with purely depressive symptoms, thus mimicking classical major depression. In such cases, corticosteroid therapy may be an effective treatment option. PMID- 27268006 TI - Study protocol: realist evaluation of effectiveness and sustainability of a community health workers programme in improving maternal and child health in Nigeria. AB - BACKGROUND: Achievement of improved maternal and child health (MCH) outcomes continues to be an issue of international priority, particularly for sub-Saharan African countries such as Nigeria. Evidence suggests that the use of Community Health Workers (CHWs) can be effective in broadening access to, and coverage of, health services and improving MCH outcomes in such countries. METHODS/DESIGN: In this paper, we report the methodology for a 5-year study which aims to evaluate the context, processes, outcomes and longer-term sustainability of a Nigerian CHW scheme. Evaluation of complex interventions requires a comprehensive understanding of intervention context, mechanisms and outcomes. The multidisciplinary and mixed-method realist approach will facilitate such evaluation. A favourable policy environment within which the study is conducted will ensure the successful uptake of results into policy and practice. A realist evaluation provides an overall methodological framework for this multidisciplinary and mixed methods research, which will be undertaken in Anambra state. The study will draw upon health economics, social sciences and statistics. The study comprises three steps: (1) initial theory development; (2) theory validation and (3) theory refinement and development of lessons learned. Specific methods for data collection will include in-depth interviews and focus group discussions with purposefully identified key stakeholders (managers, service providers and service users), document reviews, analyses of quantitative data from the CHW programme and health information system, and a small-scale survey. The impact of the programme on key output and outcome indicators will be assessed through an interrupted time-series analysis (ITS) of monthly quantitative data from health information system and programme reports. Ethics approvals for this study were obtained from the University of Leeds and the University of Nigeria. DISCUSSION: This study will provide a timely and important contribution to health systems strengthening specifically within Anambra state in southeast Nigeria but also more widely across Nigeria. This paper should be of interest to researchers who are interested in adapting and applying robust methodologies for assessing complex health system interventions. The paper will also be useful to policymakers and practitioners who are interested in commissioning and engaging in such complex evaluations to inform policies and practices. PMID- 27268008 TI - Socioeconomic factors and burn. The challenges of poverty and social gradient in our tumultuous world. PMID- 27268007 TI - Rapid identification of fungi in culture-negative clinical blood and respiratory samples by DNA sequence analyses. AB - BACKGROUND: Clinical diagnoses of fungal infections often rely upon culture techniques followed by microscopic examination of positive cultures and histopathological specimens. Culturing of microorganisms is prone to false negatives, while microscopy methods can be complicated by atypical phenotypes and organisms that are morphologically indistinguishable in tissues. Delays in diagnoses (or the lack thereof) and inaccurate identification of infectious organisms contribute to increased morbidity and mortality in patients. METHODS: Two-hundred randomized, heterogeneous patient blood and respiratory samples that were culture-negative were tested using polymerase chain reaction (PCR) amplification of internal transcribed spacer regions of ribosomal RNA genes utilizing panfungal primers. Amplicons were sequenced, subjected to sequence similarity searches, and compared using phylogenetic analyses. RESULTS: Thirteen fungal sequences were detected in three whole-blood samples and nine respiratory samples. Bioinformatic analyses were performed which indicated the presence of multiple pathogens and potential pathogens. CONCLUSIONS: The results from this pilot study demonstrate the utility of PCR assays and sequence analyses in clinical tests for fungi to facilitate rapid diagnosis and appropriate treatments to deal with the false negatives from culture results. PMID- 27268009 TI - Steam vaporizers: A danger for paediatric burns. AB - BACKGROUND: Steam vaporizers are used to humidify air in dry environments. They are marketed to moisten children's airway secretions and thus to help relieve symptoms associated with upper respiratory tract infections. Unfortunately the steam emitted from the unit can also pose a significant risk of burns to children. Our study aimed to ascertain patterns of injury and treatment outcomes from steam burns resulting from these devices. Potential preventative measures are discussed. METHODS: Children who had sustained vaporizer scald burns were identified at the outpatient burns clinic over a 10-month period (November 2014 August 2015). Medical records were reviewed retrospectively and data collected on pattern of injury, management and outcomes. RESULTS: Ten children were treated for vaporizer steam burns over the study period. The mean age was 1.6 years and 8 (80%) patients were male. Operative intervention was undergone in 5 (50%) cases; four acutely and one as a secondary reconstructive procedure. Hand burns accounted for 8 (80%) of cases. CONCLUSIONS: Steam vaporizers can cause significant burns in the paediatric population. Toddlers were most at risk, frequently sustaining hand burns that underwent skin grafting. Greater public awareness of the danger is indicated and measures to prevent such injuries should be addressed by appropriate authorities. PMID- 27268010 TI - The burned ear; possibilities and challenges in framework reconstruction and coverage. AB - Ear reconstruction remains a challenging procedure, especially in burn victims. The ear is particularly vulnerable to thermal injury because of its location and the thin integument. The thermal injury could subsequently include skin and the deeper located auricular cartilage framework. This type of injury could have long lasting mutilating effect not only because the ear's morphology is mainly related to this framework but also because it will not recover or regenerate once injured. Grafts of costal cartilage or synthetic materials might replace missing cartilage. However, the poor quality of the adjacent skin and subcutaneous tissues makes the reconstruction of a burned ear an even more daunting procedure than congenital or many oncologic indications. As such, regeneration of the skin will be the next step in reconstruction of the burned ear. There is still much development and research to be done, but encouraging results have been shown in tissue engineering of skin and cartilage. Furthermore, 3D (bio)printing of cartilage to facilitate reproduction of the ear's complex shape certainly has potential and might find an interesting role in ear reconstruction. In this review, different clinical challenges and options for ear reconstruction in burn patients are described. Subsequently, although still far from large scale clinical application, state of the art developments in the field of tissue engineering and 3D (bio)printing are also discussed. PMID- 27268011 TI - Systematic review and meta-analysis of complications and outcomes of obese patients with burns. AB - Obesity has been described as a factor that contributes to poorer outcomes and more severe complications in burned patients. We thus aimed to meta-analyse the literature present regarding the extent to which obesity contributes to the prevalence of various complications in burns. We searched MEDLINE, Science Direct and Web of Science for 363 articles. Eventually, we selected only 7 articles for our analysis based on our selection criteria. Data was analysed via Review Manager 5.3, using Mantel-Haenszel statistics and random effect models. Length of stay and mortality rates were significantly different for obese patients compared to non-obese patients at a Mean Difference (MD) of 2.16 (95% CI=0.42-3.87; I2=0; p=0.01) and Odds Ratio (OR)=1.97 (95% CI=1.07-3.46; I2=65%; p=0.03) respectively. Number of wound infections, number of burn operations and length of ICU stay were not found to be statistically different. We postulate that our significant findings are due to the proinflammatory state and poorer glycemic control in obese patients. As our review was limited by the few articles currently available in the literature, it is suggested that more studies of high quality be performed to better understand the implications of obesity in burns. PMID- 27268012 TI - The Parkland Burn Center experience with 297 cases of child abuse from 1974 to 2010. AB - INTRODUCTION: Pediatric burns due to abuse are unfortunately relatively common, accounting for 5.8-8.8% of all cases of abuse annually. Our goal was to evaluate our 36-year experience in the evaluation and management of the victims of abuse in the North Texas area. METHODS: A prospectively maintained database containing records on all admissions from 1974 through 2010 was queried for all patients aged less than 18 years. Patients admitted for management of a non-burn injury were excluded from the analysis. RESULTS: Of 5,553 pediatric burn admissions, 297 (5.3%) were due to abuse. Children with non-accidental injuries tended to be younger (2.1 vs. 5.0 years, p<0.0001) and male (66.0 vs. 56.5%, p=0.0008). Scald was the most common mechanism of injury overall (44.8%), and was also the predominant cause of inflicted burns (89.6 vs. 42.3%, p<0.0001). Multivariate logistic regression identified age, gender, presence of a scald, contact, or chemical burn, and injury to the hands, bilateral feet, buttocks, back, and perineum to be significant predictors of abuse. Victims of abuse were also found to have worse outcomes, including mortality (5.4 vs. 2.3%, p=0.0005). After adjusting for age, mechanism of injury, and burn size, abuse remained a significant predictor of mortality (OR 3.3, 95% CI 1.5-7.2) CONCLUSIONS: Clinicians should approach all burn injuries in young children with a high index of suspicion, but in particular those with scalds, or injuries to the buttocks, perineum, or bilateral feet should provoke suspicion. Burns due to abuse are associated with worse outcomes, including length of stay and mortality. PMID- 27268014 TI - FO-SPR based dextrose sensor using Ag/ZnO nanorods/GOx for insulinoma detection. AB - In this piece of work, a fiber optic sensor has been fabricated and characterized using surface plasmon resonance for dextrose sensing. The concentration range used in this study is for diagnosing the cases of hypoglycaemia especially in suppression tests of insulinoma. Insulinoma is a medical case in which the person is recognized being hypoglycaemic with the blood dextrose level falling down to 2.2mM or less. Thus, the sensor has been characterized for the dextrose concentration range of 0 mM-10mM including the cases of normal blood dextrose range. Coatings of silver layer and zinc oxide nanorods have been carried out on the bare core fiber with a dual role of zinc oxide followed by immobilization of glucose oxidase. A three stage optimization procedure has been adopted for the best performance of the sensor. Absorbance spectra have been plotted and peak absorbance wavelengths have been extracted for each concentration chosen along with the sensitivities. The results have been made conclusive with control experiments. The probe has also been tested on sample having blood serum to check the reliability of the sensor. The sensor shows better selectivity and response time along with its real time applications, online monitoring, remote sensing and reusability. PMID- 27268013 TI - Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes. AB - Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. PMID- 27268015 TI - Effect of interpregnancy interval on adverse pregnancy outcomes in northern Tanzania: a registry-based retrospective cohort study. AB - BACKGROUND: Both short and long interpregnancy intervals have been associated with an increased risk of adverse pregnancy outcomes. There is limited information about the impact of interpregnancy interval on pregnancy (IPI) outcomes in Tanzania. The objective of this study was to assess the effect of IPI on adverse pregnancy outcomes. METHODS: We performed a retrospective cohort study using maternally-linked data from Kilimanjaro Christian Medical Centre (KCMC) birth registry. A total of 17,030 singlet births from women who delivered singleton infant at KCMC from 2000 to 2010 were studied. Women with multi-fetal gestations and those who were referred from rural areas for various medical reasons were excluded. Outcome variables were preterm birth, low birth weight infants and perinatal death. A multiple logistic regression was used to assess the association between IPI and pregnancy outcomes. RESULTS: The median IPI was 36 months. Compared with IPIs of 24-36 months (referent group), short interpregnancy intervals (<24 months) was associated with preterm delivery (OR 1 . 52; 95 % CI 1.31-1.74); low birth weight (OR 1 . 61; 95 % CI 1 . 34-1.72) and perinatal death, (OR 1 . 63; 95 % CI 1.22-1.91). The IPI of 37-59 months or longer were also associated with higher risks of preterm birth and low birth weight, but not with perinatal death. CONCLUSIONS: Our study confirmed that both short and long IPI are independent risk factors for adverse pregnancy outcomes. These finding emphasize the importance of providing support for family planning programs which will support optimal IPI and improve pregnancy outcomes. PMID- 27268016 TI - Understanding Zika virus pathogenesis: an interview with Catherine Spong. AB - A recent outbreak of Zika virus has been linked to fetal abnormalities in pregnant women who have been infected. The scientific community is working toward understanding Zika virus pathogenesis to better manage affected women and children. In an interview with Dr. Catherine Spong, we discuss the aims and challenges of a forthcoming longitudinal study of a cohort of pregnant women in areas of current active Zika virus transmission. PMID- 27268018 TI - Community-Based Health Education Programs Designed to Improve Clinical Measures Are Unlikely to Reduce Short-Term Costs or Utilization Without Additional Features Targeting These Outcomes. AB - Stakeholders often expect programs for persons with chronic conditions to "bend the cost curve." This study assessed whether a diabetes self-management education (DSME) program offered as part of a multicomponent initiative could affect emergency department (ED) visits, hospital stays, and the associated costs for an underserved population in addition to the clinical indicators that DSME programs attempt to improve. The program was implemented in Camden, New Jersey, by the Camden Coalition of Healthcare Providers to address disparities in diabetes care. Data used are from medical records and from patient-level information about hospital services from Camden's hospitals. Using multivariate regression models to control for individual characteristics, changes in utilization over time and changes relative to 2 comparison groups were assessed. No reductions in ED visits, inpatient stays, or costs for participants were found over time or relative to the comparison groups. High utilization rates and costs for diabetes are associated with longer term disease progression and its sequelae; thus, DSME or peer support may not affect these in the near term. Some clinical indicators improved among participants, and these might lead to fewer costly adverse health events in the future. DSME deployed at the community level, without explicit segmentation and targeting of high health care utilizers or without components designed to affect costs and utilization, should not be expected to reduce short term medical needs for participating individuals or care-seeking behaviors such that utilization is reduced. Stakeholders must include financial outcomes in a program's design if those outcomes are to improve. PMID- 27268017 TI - c-Jun N-terminal kinase activation has a prognostic implication and is negatively associated with FOXO1 activation in gastric cancer. AB - BACKGROUND: Since the biological function of c-Jun N-terminal kinase (JNK) in gastric cancer remains unclear, we investigated the clinical significance of JNK activation and its association with FOXO1 activation. METHODS: Immunohistochemical tissue array analysis of 483 human gastric cancer specimens was performed, and the results of the immunostaining were quantified. The correlation between JNK activation (nuclear staining for pJNK) and clinicopathological features, the proliferation index, prognosis or FOXO1 inactivation (cytoplasmic staining for pFOXO1) was analyzed. The SNU-638 gastric cancer cell line was used for in vitro analysis. RESULTS: Nuclear staining of pJNK was found in 38 % of the gastric carcinomas and was higher in the early stages of pTNM (P < 0.001). pJNK staining negatively correlated with lymphatic invasion (P = 0.034) and positively correlated with intestinal type by Lauren's classification (P = 0.037), Ki-67-labeling index (P < 0.001), cyclin D1 (P = 0.045), cyclin E (P < 0.001) and pFOXO1 (P < 0.001). JNK activation correlated with a longer patients survival (P =0.008) and patients with a JNK-active and FOXO1-inactive tumor had a higher survival rate than the remainder of the population (P = 0.004). In vitro analysis showed that JNK inhibition by SP600125 in SNU-638 cells decreased cyclin D1 protein expression and increased FOXO1 activation. Further, JNK inhibition markedly suppressed colony formation, which was partially restored by FOXO1 shRNA expression. CONCLUSIONS: Our results indicate that JNK activation may serve as a valuable prognostic factor in gastric cancer, and that it is implicated in gastric tumorigenesis, at least in part, through FOXO1 inhibition. PMID- 27268019 TI - Alloyed Crystalline Au-Ag Hollow Nanostructures with High Chemical Stability and Catalytic Performance. AB - For bimetallic nanoparticles (NPs), the degree of alloying is beginning to be recognized as a significant factor affecting the NP properties. Here, we report an alloyed crystalline Au-Ag hollow nanostructure that exhibits a high catalytic performance, as well as structural and chemical stability. The Au-Ag alloyed hollow and porous nanoshell structures (HPNSs) with different morphologies and subnanoscale crystalline structures were synthesized by adjusting the size of the sacrificial Ag NPs via a galvanic replacement reaction. The catalytic activities of the nanomaterials were evaluated by the model reaction of the catalytic reduction of p-nitrophenol by NaBH4 to p-aminophenol. The experimental results show that the subnanoscale crystalline structure of the Au-Ag bimetallic HPNSs has much greater significance than the apparent morphology does in determining the catalytic ability of the nanostructures. The Au-Ag alloyed HPNSs with better surface crystalline alloying microstructures and open morphologies were found to exhibit much higher catalytic reaction rates and better cyclic usage efficiencies, probably because of the better dispersion of active Au atoms within these materials. These galvanic replacement-synthesized alloyed Au-Ag HPNSs, fabricated by a facile method that avoids Ag degradation, have potential applications in catalysis, nanomedicine (especially in drug/gene delivery and cancer theranostics), and biosensing. PMID- 27268021 TI - Operational research as implementation science: definitions, challenges and research priorities. AB - BACKGROUND: Operational research (OR) is the discipline of using models, either quantitative or qualitative, to aid decision-making in complex implementation problems. The methods of OR have been used in healthcare since the 1950s in diverse areas such as emergency medicine and the interface between acute and community care; hospital performance; scheduling and management of patient home visits; scheduling of patient appointments; and many other complex implementation problems of an operational or logistical nature. DISCUSSION: To date, there has been limited debate about the role that operational research should take within implementation science. I detail three such roles for OR all grounded in upfront system thinking: structuring implementation problems, prospective evaluation of improvement interventions, and strategic reconfiguration. Case studies from mental health, emergency medicine, and stroke care are used to illustrate each role. I then describe the challenges for applied OR within implementation science at the organisational, interventional, and disciplinary levels. Two key challenges include the difficulty faced in achieving a position of mutual understanding between implementation scientists and research users and a stark lack of evaluation of OR interventions. To address these challenges, I propose a research agenda to evaluate applied OR through the lens of implementation science, the liberation of OR from the specialist research and consultancy environment, and co-design of models with service users. Operational research is a mature discipline that has developed a significant volume of methodology to improve health services. OR offers implementation scientists the opportunity to do more upfront system thinking before committing resources or taking risks. OR has three roles within implementation science: structuring an implementation problem, prospective evaluation of implementation problems, and a tool for strategic reconfiguration of health services. Challenges facing OR as implementation science include limited evidence and evaluation of impact, limited service user involvement, a lack of managerial awareness, effective communication between research users and OR modellers, and availability of healthcare data. To progress the science, a focus is needed in three key areas: evaluation of OR interventions, embedding the knowledge of OR in health services, and educating OR modellers about the aims and benefits of service user involvement. PMID- 27268022 TI - [Validity of anthropometric measurements and weight perceptions reported by relatives of children under 4 years old]. AB - OBJECTIVE: To assess the validity of weight and height measurements reported by parents and the perception of their children's weight status in order to assess the prevalence of overweight children under 4 years old. METHODS: Cross-sectional study. Anthropometric data was collected by self-report questionnaires completed by parents of children 3-45 months old: 1) information from paediatric check-ups (gold standard); 2) information reported from the home environment; and 3) data from individual perceptions. WHO standards were used. RESULTS: Reported height was underestimated, thus reported weight/height and BMI/age were overestimated. Overweight prevalence according to paediatric check-ups was 18.6%, compared to 26.5% reported prevalence, showing a moderate concordance (Kappa: 0.47 [0.34 0.60]), 70% sensitivity and 84% specificity. Subjective perception was 11.2%, representing 30% sensitivity and 93% specificity. CONCLUSIONS: The reported information has little validity for population-based studies, as height is underestimated and overweight status is not correctly perceived due to distortion of individual perception. Questionnaires must be validated and awareness raised among families. PMID- 27268023 TI - Social security status and mortality in Belgian and Spanish male workers. AB - OBJECTIVE: To assess differences in mortality rates between social security statuses in two independent samples of Belgian and Spanish male workers. METHODS: Study of two retrospective cohorts (Belgium, n=23,607; Spain, n=44,385) of 50-60 year old male employees with 4 years of follow-up. Mortality rate ratios (MRR) were estimated using Poisson regression models. RESULTS: Mortality for subjects with permanent disability was higher than for the employed, for both Belgium [MRR=4.56 (95% CI: 2.88-7.21)] and Spain [MRR=7.15 (95% CI: 5.37-9.51)]. For the unemployed/early retirees, mortality was higher in Spain [MRR=1.64 (95% CI: 1.24 2.17)] than in Belgium [MRR=0.88 (95% CI: 0.46-1.71)]. CONCLUSION: MRR differences between Belgium and Spain for unemployed workers could be partly explained because of differences between the two social security systems. Future studies should further explore mortality differences between countries with different social security systems. PMID- 27268024 TI - Do low-risk nulliparous women with abnormal uterine artery Doppler in the third trimester have poorer perinatal outcomes? A longitudinal prospective study on uterine artery Doppler in low-risk nulliparous women and correlation with pregnancy outcomes. AB - OBJECTIVE: To evaluate uterine artery (UtA) Doppler over the course of pregnancy in low-risk nulliparous women and to analyze whether an abnormal uterine artery pulsatility index (UtA-PI) at a 32-34 week' scan implies poorer perinatal outcomes. METHODS: An observational prospective study was carried out including 616 low-risk nulliparous women. Women with any of the following were excluded: fetal abnormalities, multiple pregnancy, and heparin, metformin or hypotensive treatment. Maternal characteristics, mean arterial pressure measurements and UtA Doppler findings were recorded longitudinally. RESULTS: Complete pregnancy data were available for 489/616 women (79.3%). Of these, 385 women had a normal UtA-PI throughout pregnancy (Group 0), while 50 (10.1%) had an UtA-PI > 95th percentile in the first or the second trimester that normalized in the third trimester (Group 1), and 56 (11.4%) had an abnormal UtA-PI in the third trimester (Group 2). We found that the rate of pre-eclampsia (PE) was higher in Group 2 (7/56 versus 4/435, p = 0.003) as was the rate of intrauterine growth restriction (IUGR) (6/56 versus 14/435, p = 0.02). CONCLUSIONS: Low-risk nulliparous women with abnormal UtA Doppler findings in the third trimester are at a higher risk of developing PE and having a baby with IUGR. PMID- 27268026 TI - Re: Moxifloxacin should not be discounted in the treatment of bacterial meningitis. PMID- 27268027 TI - Vaccination with endosomal unknown epitopes produces therapeutic response in rheumatoid arthritis patients and modulates adjuvant arthritis of rats. AB - BACKGROUND: Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and freed the autoantigens which in turn stimulated the immunoregulatory rather than autoreactive T cell response in rheumatoid patients. Here, we hypothesize that disruption in vitro of peripheral blood mononuclear cells, by freeze/thawing or by lytic action of Rifamycin SV, would induce the release of endosomal pathogenic autoantigens from APCs present in the circulation, which could then be isolated from degrading enzymes by ultrafiltration. METHODS: The preparation of the ultrafiltrates are based on the rupture of PBMCs (5 * 10(6) cells/mL) by the addition of Rifamycin SV in culture (250 MUg/mL), which causes the lysis of 90 % of the cells in 3 h, or by three cycles of freeze/thawing of the PBMC, from -80 degrees C to room temperature. The lysate and the fragmented cells were then centrifuged and ultrafiltered by passage through a filtration device with a cut-off of 10 kDa. Also the synovial fluid was subjected to ultrafiltration. RESULTS AND CONCLUSIONS: At clinical monitoring of the 30th day, 22/58 (38 %) patients subcutaneously treated with the autologous ultrafiltrate prepared by the freeze/thawing of PBMCs reached an ACR20. Comparable results were obtained with the other two ultrafiltrates. Cell cultures The addition of ultrafiltrates to rheumatoid PBMCs cultures led to the upregulation of a marker for T-regulatory cells, and downregulation of a cell proliferation marker; changes that together have the meaning of a global immunomodulatory response and that only a specific antigen (ultrafiltrate UF-f/t) might induce in the rheumatoid patient, probably by activating pre-existing protective network. Experimental arthritis All the ultrafiltrates except that prepared by Rifamycin SV were able to modulate the adjuvant arthritis in rats. In particular, longlasting synovial fluid induced a significant reduction of the severity of subsequent arthritis (p < 0.01) while SF from recent RA effusion (5 10 days after a previous complete extraction) and knee osteoarthrosis were ineffective. It is reasonable to assume there are at least two unknown endosomal immunoactive epitopes; one developing its immunotherapeutic property in RA, and the other, related to the molecule of HSP60, reduces the severity of oncoming arthritis. Both epitopes are present in humans, have a molecular weight of <=10 kDa and do not appear to be bystander antigens. Please see Additional file 1 for the abstract in Italian. PMID- 27268028 TI - Combinatorial Pairwise Assembly Efficiently Generates High Affinity Binders and Enables a "Mix-and-Read" Detection Scheme. AB - We show that a combinatorial library constructed by random pairwise assembly of low affinity binders can efficiently generate binders with increased affinity. Such a library based on the Sso7d scaffold, from a pool of low affinity binders subjected to random mutagenesis, contained putative high affinity clones for a model target (lysozyme) at higher frequency than a library of monovalent mutants generated by random mutagenesis alone. Increased binding affinity was due to intramolecular avidity generated by linking binders targeting nonoverlapping epitopes; individual binders of KD ~ 1.3 MUM and 250 nM produced a bivalent binder with apparent KD ~ 2 nM. Furthermore, the bivalent protein retained thermal stability (TM = 84.5 degrees C) and high recombinant expression yields in E. coli. Finally, when binders comprising the bivalent protein are fused to two of the three fragments of tripartite split-green fluorescent protein (GFP), target-dependent reconstitution of fluorescence occurs, thereby enabling a "mix and-read" assay for target quantification. PMID- 27268029 TI - Adverse effects and tolerability of beta blockers. PMID- 27268025 TI - Potential neuroprotective properties of epigallocatechin-3-gallate (EGCG). AB - Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) enforce an overwhelming social and economic burden on society. They are primarily characterized through the accumulation of modified proteins, which further trigger biological responses such as inflammation, oxidative stress, excitotoxicity and modulation of signalling pathways. In a hope for cure, these diseases have been studied extensively over the last decade to successfully develop symptom-oriented therapies. However, so far no definite cure has been found. Therefore, there is a need to identify a class of drug capable of reversing neural damage and preventing further neural death. This review therefore assesses the reliability of the neuroprotective benefits of epigallocatechin-gallate (EGCG) by shedding light on their biological, pharmacological, antioxidant and metal chelation properties, with emphasis on their ability to invoke a range of cellular mechanisms in the brain. It also discusses the possible use of nanotechnology to enhance the neuroprotective benefits of EGCG. PMID- 27268030 TI - Health Disparities Research Among Small Tribal Populations: Describing Appropriate Criteria for Aggregating Tribal Health Data. AB - In response to community concerns, we used the Tribal Participatory Research framework in collaboration with 5 American-Indian communities in Washington, Idaho, and Montana to identify the appropriate criteria for aggregating health data on small tribes. Across tribal sites, 10 key informant interviews and 10 focus groups (n = 39) were conducted between July 2012 and April 2013. Using thematic analysis of focus group content, we identified 5 guiding criteria for aggregating tribal health data: geographic proximity, community type, environmental exposures, access to resources and services, and economic development. Preliminary findings were presented to focus group participants for validation at each site, and a culminating workshop with representatives from all 5 tribes verified our final results. Using this approach requires critical assessment of research questions and study designs by investigators and tribal leaders to determine when aggregation or stratification is appropriate and how to group data to yield robust results relevant to local concerns. At project inception, tribal leaders should be consulted regarding the validity of proposed groupings. After regular project updates, they should be consulted again to confirm that findings are appropriately contextualized for dissemination. PMID- 27268031 TI - Androgen Deprivation Therapy and the Incidence of Inflammatory Bowel Disease in Patients With Prostate Cancer. AB - Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer. By lowering androgen levels, ADT inhibits the progression of prostate cancer, but it may also affect gut autoimmunity. We investigated the association between ADT and the incidence of inflammatory bowel disease using a cohort of 31,842 men newly diagnosed with prostate cancer between 1988 and 2014, identified in the United Kingdom Clinical Practice Research Datalink. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays, with nonuse as the reference category. During 133,018 person years of follow-up, 48 men were newly diagnosed with ulcerative colitis (incidence rate (IR) = 36/100,000 person-years (PY)) and 12 were diagnosed with Crohn's disease (IR = 9/100,000 PY). In Cox proportional hazards models, ADT was associated with a decreased risk of ulcerative colitis (IR = 24/100,000 PY vs. IR = 50/100,000 PY; hazard ratio = 0.52, 95% confidence interval: 0.28, 0.99) and a nonsignificant decreased risk of Crohn's disease (hazard ratio = 0.38, 95% confidence interval: 0.11, 1.37). These findings indicate that the use of ADT may be associated with intestinal autoimmunity. Further research is warranted to replicate these findings and assess their clinical significance. PMID- 27268032 TI - Associations Between Maternal Pregravid Obesity and Gestational Diabetes and the Timing of Pubarche in Daughters. AB - We investigated whether in utero exposure to maternal pregravid obesity and/or gestational diabetes mellitus (GDM) was associated with early puberty in girls. We used data from a longitudinal study of 421 mother-daughter pairs enrolled in an integrated health services organization, Kaiser Permanente Northern California (2005-2012). Girls aged 6-8 years were followed annually through ages 12-14 years. Onset of puberty was assessed using study clinic-based Tanner staging. We examined associations of self-reported pregravid obesity and maternal GDM with timing of the daughter's transition to pubertal maturation stage 2 or above for development of breasts and pubic hair, using accelerated failure time regression models with interval censoring to estimate time ratios and hazard ratios and corresponding 95% confidence intervals. Maternal obesity (pregravid body mass index (BMI; weight (kg)/height (m)(2)) >=30) was associated with a daughter's earlier transition to breast and pubic hair stage 2+ in comparison with girls whose mothers had pregravid BMI <25. These associations were attenuated and not statistically significant after adjustment for covariates. Girls whose mothers had both pregravid BMI >=25 and GDM were at higher risk of an earlier transition to pubic hair stage 2+ than those whose mothers had neither condition (adjusted time ratio = 0.89, 95% confidence interval: 0.83, 0.96; hazard ratio = 2.97, 95% confidence interval: 1.52, 5.83). These findings suggest that exposure to maternal obesity and hyperglycemia places girls at higher risk of earlier pubarche. PMID- 27268033 TI - Hybrid Antifouling and Antimicrobial Coatings Prepared by Electroless Co Deposition of Fluoropolymer and Cationic Silica Nanoparticles on Stainless Steel: Efficacy against Listeria monocytogenes. AB - Controlling formation, establishment, and proliferation of microbial biofilms on surfaces is critical for ensuring public safety. Herein, we report on the synthesis of antimicrobial nanoparticles and their co-deposition along with fluorinated nanoparticles during electroless nickel plating of stainless steel. Plating bath composition is optimized to ensure sufficiently low surface energy to resist fouling and microbial adhesion as well as to exert significant (>99.99% reduction) antimicrobial activity against Listeria monocytogenes. The resulting coatings present hybrid antifouling and antimicrobial character, can be applied onto stainless steel, and do not rely on leaching or migration of the antimicrobial nanoparticles to be effective. Such coatings can support reducing public health issues related to microbial cross-contamination in areas such as food processing, hospitals, and water purification. PMID- 27268034 TI - Time course decomposition of cell heterogeneity in TFEB signaling states reveals homeostatic mechanisms restricting the magnitude and duration of TFEB responses to mTOR activity modulation. AB - BACKGROUND: TFEB (transcription factor EB) regulates metabolic homeostasis through its activation of lysosomal biogenesis following its nuclear translocation. TFEB activity is inhibited by mTOR phosphorylation, which signals its cytoplasmic retention. To date, the temporal relationship between alterations to mTOR activity states and changes in TFEB subcellular localization and concentration has not been sufficiently addressed. METHODS: mTOR was activated by renewed addition of fully-supplemented medium, or inhibited by Torin1 or nutrient deprivation. Single-cell TFEB protein levels and subcellular localization in HeLa and MCF7 cells were measured over a time course of 15 hours by multispectral imaging cytometry. To extract single-cell level information on heterogeneous TFEB activity phenotypes, we developed a framework for identification of TFEB activity subpopulations. Through unsupervised clustering, cells were classified according to their TFEB nuclear concentration, which corresponded with downstream lysosomal responses. RESULTS: Bulk population results revealed that mTOR negatively regulates TFEB protein levels, concomitantly to the regulation of TFEB localization. Subpopulation analysis revealed maximal sensitivity of HeLa cells to mTOR activity stimulation, leading to inactivation of 100 % of the cell population within 0.5 hours, which contrasted with a lower sensitivity in MCF7 cells. Conversely, mTOR inhibition increased the fully active subpopulation only fractionally, and full activation of 100 % of the population required co inhibition of mTOR and the proteasome. Importantly, mTOR inhibition activated TFEB for a limited duration of 1.5 hours, and thereafter the cell population was progressively re-inactivated, with distinct kinetics for Torin1 and nutrient deprivation treatments. CONCLUSION: TFEB protein levels and subcellular localization are under control of a short-term rheostat, which is highly responsive to negative regulation by mTOR, but under conditions of mTOR inhibition, restricts TFEB activation in a manner dependent on the proteasome. We further identify a long-term, mTOR-independent homeostatic control negatively regulating TFEB upon prolonged mTOR inhibition. These findings are of relevance for developing strategies to target TFEB activity in disease treatment. Moreover, our quantitative approach to decipher phenotype heterogeneity in imaging datasets is of general interest, as shifts between subpopulations provide a quantitative description of single cell behaviour, indicating novel regulatory behaviors and revealing differences between cell types. PMID- 27268035 TI - VEGF receptor signal transduction - A brief update. AB - Vascular endothelial growth factor (VEGF) signal transduction through receptor tyrosine kinases VEGF receptor-1, -2 and -3 is of crucial importance for monocytes/macrophages, blood vascular endothelial and lymphatic endothelial cells both in physiology and in a number of pathologies notably cancer. This brief review summarizes the current status of VEGF receptor signaling with emphasis on in vivo data. PMID- 27268036 TI - Discovering cardiac pericyte biology: From physiopathological mechanisms to potential therapeutic applications in ischemic heart disease. AB - Microvascular pericytes and the more recently discovered adventitial pericyte like progenitor cells are a subpopulation of vascular stem cells closely associated with small and large blood vessels respectively. These populations of perivascular cells are remarkably abundant in the heart. Pericytes control important physiological processes such as angiogenesis, blood flow and vascular permeability. In the heart, this pleiotropic activity makes pericytes extremely interesting for applications in regenerative medicine. On the other hand, dysfunction of pericytes could participate in the pathogenesis of cardiovascular disease, such as arterial hypertension, fibro-calcific cardiovascular remodeling, myocardial edema and post-ischemic coronary no-reflow. On a therapeutic standpoint, preclinical studies in small animal models of myocardial infarction have demonstrated the healing potential of pericytes transplantation, which has been ascribed to direct vascular incorporation and paracrine pro-angiogenic and anti-apoptotic activities. These promising findings open the door to the clinical use of pericytes for the treatment of cardiovascular diseases. PMID- 27268037 TI - Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families. AB - BACKGROUND: Recessive mutations in PLA2G6 have been associated with different neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation and more recently, early-onset dystonia parkinsonism. METHOD: Targeted-next generation sequencing using a custom Neurology panel, containing 758 OMIM-listed genes implicated in neurological disorders, was carried out in two index cases from two different Saudi families displaying early-onset levodopa-responsive Parkinsonism with pyramidal signs and additional clinical features. The detected mutations were verified in the index cases and available family members by direct sequencing. RESULTS AND CONCLUSION: We identified a previously described PLA2G6 homozygous p.R741Q mutation in three affected and two asymptomatic individuals from two Saudi families. Our finding reinforces the notion of the broadness of the clinical spectrum of PLA2G6-related neurodegeneration. PMID- 27268038 TI - The negative priming effect in cognitive conflict processing. AB - The present study used event-related potentials (ERPs) to investigate the specific physiological mechanisms underlying the negative nature of cognitive conflict and its influence on affective word evaluations. The present study used an affective priming paradigm where Stroop stimuli were presented for 200ms after which affective target words had to be evaluated as being positive or negative. Behavioral results showed that reaction times (RTs) were shorter for positive targets following congruent primes relative to incongruent primes, and for negative targets following incongruent primes relative to congruent primes. The ERP results showed that the N2 amplitude (200-300ms) for incongruent stimuli was significantly larger than for congruent stimuli in the Stroop task, which indicated a significant conflict effect. Moreover, the N400 amplitude (300-500ms) was smaller for negative words following incongruent primes relative to congruent primes, and for positive words following congruent primes relative to incongruent primes. The results demonstrated that cognitive conflict modulated both behavioral and electrophysiological correlates of subsequent emotional processing, consistent with its hypothesized registration as an aversive signal. PMID- 27268039 TI - Single session intermittent theta-burst stimulation on the left premotor cortex does not alleviate freezing of gait in Parkinson's disease. AB - OBJECTIVE: To investigate the efficiency of intermittent theta-burst stimulation (iTBS) to alleviate the symptoms of freezing of gait (FoG) in Parkinson's disease (PD). METHODS: We performed a cross-over, sham-controlled study of patients with severe PD, bilateral motor signs and debilitating, severe FoG, that was levodopa sensitive but not controlled by optimal dopatherapy. We applied iTBS to the left premotor cortex and measured FoG, gait initiation and continuous gait, before and immediately after the iTBS session. All patients received sham and true iTBS with a one-week interval and in randomized order. RESULTS: 15 patients were included in the study. Recordings were performed under usual medication and all patients always showed unresponsive freezing. The pre- and post-stimulation gait trajectories did not differ in terms of the mean trajectory completion time or the percent time with FoG. The percent time with FoG was 6% greater after sham stimulation and 3% lower after iTBS (p>0.05). Visual cueing modified gait initiation and continuous gait but these latter were not influenced by rTMS. CONCLUSIONS: The present study provides Class I evidence that iTBS of the left premotor cortex does not alleviate FoG in PD. PMID- 27268040 TI - The neural mechanism of biomechanical constraints in the hand laterality judgment task: A near-infrared spectroscopy study. AB - The mental rotation (MR) task is defined as a discrimination task between mirror reversed images involving discrepancy in angular orientation. Various studies have shown that the MR task likely causes mental imagery, that is, visual and/or motor imagery, depending on stimulus types. When figures of rotated hands are presented to be identified as a left or right hand, reaction times (RTs) usually show an effect of biomechanical constraints (BC): a hand in a position difficult to reach with a real movement results in longer RTs. The BC effect as a marker of motor imagery has been investigated by brain function measures (fMRI, PET, EEG and MEG) as well as by RTs. Unlike other neuroimaging techniques, NIRS (near infrared spectroscopy) imposes few physical constraints on participants and is relatively unaffected by motion artifact, which permits serial assessments of tasks in relaxed and natural environment. Focusing on these advantages, a NIRS study on motor imagery in HLJ was carried out in which we measured the brain activation during the HLJ task and a single character judgment task. In the HLJ task, both the RTs and the activity of the left superior parietal lobe (SPL) showed an interaction between Hand (left, right) and Orientation (135 degrees , 225 degrees ) i.e., the BC effect, but not in the character judgment task. More specifically, in the analysis of BC-related activity of SPL, although the Hand*Orientation interaction was significant, the left SPL for the left hand significantly increased from 135 degrees to 225 degrees , but the reversed increase (from 225 degrees to 135 degrees ) was not found for the right hand. These results suggest that left SPL is involved in the BC effect and NIRS differentiates left hand awkwardness of right-hander in the HLJ task. PMID- 27268041 TI - In-vivo comparison of the neurotoxic potencies of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA. AB - Three botulinum neurotoxin type A (BoNT/A) products, incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA, all manufactured by different methods, are employed in clinical practice. Comparing the three BoNT/A products is difficult because their concentrations and volumes differ and the precise dose equivalence ratio is not known. We aimed to compare the neurotoxic potencies by a systematic analysis of injected volume and dose. The potency of BoNT in inducing hind limb paresis was assessed by analyzing the wheel-running performance of mice. To standardize the volume, the effect of an identical dose of incobotulinumtoxinA dissolved in different volumes of saline (15, 10, 5, and 2MUl) was studied in four groups of mice (n=13-15). The potencies of the BoNT products were then compared by injecting identical volumes (10MUl) containing different doses into both hind leg muscles. Mice injected with incobotulinumtoxinA showed a volume-dependent reduction in wheel-running, with larger volumes inducing more intense paresis. A standardized volume containing the same number of mouse units of the BoNT/A products produced different degrees of paresis. The conversion ratio of incobotulinumtoxinA and onabotulinumtoxinA is estimated to be between 1:0.75 and 1:0.5. OnabotulinumtoxinA displayed a two-fold greater potency than abobotulinumtoxinA. Doses of onabotulinumtoxinA and abobotulinumtoxinA that produce an identical severity of pareses even result in the same duration of pareses. This wheel-running assay allows one to compare the neurotoxic potency of different volumes and doses of the BoNT products in vivo. Our results argue against common clinical practice because incobotulinumtoxinA and onabotulinumtoxinA are not readily interchangeable and a two-fold dose of abobotulinumtoxinA is needed to induce an effect identical to onabotulinumtoxinA. In addition, this emphasizes that the duration of BoNT-induced effect is the same as long as equipotent doses of BoNT are injected. PMID- 27268042 TI - Effects of simulated microgravity on human brain nervous tissue. AB - During spaceflight, the negative effects of space microgravity on astronauts are becoming more and more prominent, and especially, of which on the nervous system is urgently to be solved. For this purpose tissue blocks and primary cells of nervous tissues obtained from glioma of patients were cultivated after culturing for about 7days, explanted tissues and cells were then randomly divided into two groups, one for static culture (control group, C), and the other for rotary processing for 1day, 3days, 5days, 7days and 14days (experiment group, E). Figures captured by inverted microscope revealed that, with short time rotating for 1day or 3days, morphology changes of tissue blocks were not obvious. When the rotary time was extended to 7days or 14days, it was found that cell somas is significantly larger and the ability of adhesion is declined in comparison with that in control group. Additionally, the arrangement of cells migrated from explanted tissues was disorganized, and the migration distance became shorter. In immunofluorescence analysis, beta-tubulin filaments in control group appeared to organize into bundles. While in experiment group, beta-tubulin was highly disorganized. In conclusion, simulated microgravity treatment for a week affected the morphology of nervous tissue, and caused highly disorganized distribution of cytoskeleton and the increase of cell apoptosis. These morphological changes might be one of the causes of apoptosis induced by simulated microgravity. PMID- 27268044 TI - Editorial Comment. PMID- 27268045 TI - Corrigendum to "Characterization of recombinant human diamine oxidase (rhDAO) produced in Chinese Hamster Ovary (CHO) cells" [J. Biotechnol. 227 (2016) 120 130]. PMID- 27268046 TI - Obesity and weight gain among former World Trade Center workers and volunteers. AB - A high prevalence of obesity has been observed among former World Trade Center (WTC) workers and volunteers. We hypothesized that unemployment and disability status would predict obesity. We surveyed 220 participants at the [INST] Mount Sinai WTC Clinical Center to assess their obesity and current employment and disability status, WTC occupational exposure level, medical comorbidities, and dietary and exercise habits. Bivariate and logistic regression multivariate analyses were used to explore associated risk factors. Obesity was associated with active employment status. Other significant covariates included non-Latino African American race, having a high number of comorbid chronic diseases, low exercise frequency, and not drinking any glass of juice daily. The association of obesity with active employment suggests that interventions that favor healthy habits among actively employed individuals are warranted. PMID- 27268047 TI - Adrenal Histologic Stress-Related Changes in Third Trimester Stillbirth: Frequency and Clinical-Pathologic Correlations in a Predominantly African American Population. AB - Adrenal histologic changes, including compact cell change (CCC), cystic change (CYC), and adrenal hemorrhage (AH), and their clinical correlations have only infrequently been investigated in stillbirth. We evaluated 75 3rd trimester singleton stillborns with complete autopsies (30 term; 45 preterm). 58 had unexplained stillbirth, and 17 had clinical placental abruption. The mothers were predominantly African-American (89%). CCC and CYC were diagnosed as cytoplasmic eosinophilia and cystic cavities in the definitive cortex, respectively. Adrenal changes were correlated with acute thymic involution (ATI), thymic petechiae, and clinical features, including abruption. CCC, CYC, and AH were present in 58 (77%), 51 (68%), and 15 (20%) of the 75 stillborns, respectively. CCC and CYC were frequently seen together (p<0.001). CCC and CYC were associated with higher ATI grade (p<0.001 and p=0.010, respectively). The presence of CCC, but not CYC was associated with absence of thymic petechiae (p=0.013) and was more frequent with unexplained stillbirth compared to abruption (p=0.017). AH was associated with lower ATI grade (p=0.002), with thymic petechiae (p<0.001), and with abruption (p=0.004). CYC was associated with diabetes (p=0.015). Overall, CCC and CYC were frequent findings and correlated with higher ATI grade, suggesting similar causes and time frames. CCC, but not CYC, correlated with unexplained stillbirth compared to abruption, but its high frequency in both groups limits its usefulness in their separation. AH was more frequent in the abruption group and correlated with lower ATI grade and thymic petechiae, supporting an association with sudden asphyxial death. PMID- 27268049 TI - What is the evidence for stress resistance and slowed aging? AB - Stress resistance is thought to contribute to slowed-aging, although cause and effect between the two is controversial. On October 30, 2015 researchers gathered at the Front Range Consortium on Stress Resistance and Slowed Aging in Fort Collins, CO, to discuss what the current evidence is that stress resistance imparts slowed aging. Included in that discussion was defining stress resistance, distinguishing if there are key stresses to which resistance imparts slowed aging, what models aid in our understanding of stress resistance and aging, and how to translate that knowledge into slowed aging treatment. The following article is a brief summary of that discussion and recommendations for moving forward. PMID- 27268048 TI - Use of the sit-to-stand task to evaluate motor function of older adults using telemetry. AB - BACKGROUND: Physical exercises are widely used in community programs, but not all older adults are willing to participate. Information and communication technology may solve this problem by allowing older people to participate in fitness programs at home. Use of remote instruction will facilitate physical exercise classes without requiring that participants gather at one place. The aim of this study was to examine use of a sit-to-stand task in evaluating motor function using conventional video communication in a telemetry system to enable real-time monitoring, and evaluation in physical performance of older adults at home. METHODS: The participants were 59 older individuals and 81 university students. Three physical exercise batteries were used: arm curl, figure-of-eight walk test, and functional reach. The knee extension maximum angular velocity (KEMAV) and the iliac elevation maximum velocity (IEMV) during standing up from a chair and the heel rise frequency were used in the motion-capture measurements. The results were assessed using multi-group structural equation modeling (SEM) for the young and older groups. RESULTS: Young participants consistently performed better than their older counterparts on all items. Analyses with multi-group SEM based on correlations between items yielded a good model-fit for the data. Among all path diagrams for IEMV and KEMAV in the older and young groups, paths from muscular strength to skillfulness showed significant effects. The path from the IEMV to muscular strength was also significant in the older group. CONCLUSIONS: Multi group SEM suggested that video-based measurements of IEMV during sit-to-stand motion can estimate muscular strength, which suggests that remote monitoring of physical performance can support wellness of community-dwelling older adults. PMID- 27268050 TI - Meta-analysis of diagnostic accuracy of neutrophil CD64 for neonatal sepsis. AB - BACKGROUND: The aim of this study was to systematically evaluate the diagnostic performance of nCD64 for neonatal sepsis. METHODS: Computer retrieval was conducted for the databases of PubMed, Embase, and Springer databases up to March 18, 2015 to select the relevant studies on nCD64 and neonatal sepsis. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and 95 % confidence intervals (CI) for diagnostic efficiency of nCD64 were pooled. In addition, the summary receiver operating characteristic (SROC) curve was also conducted based on the sensitivity and specificity. RESULTS: Seventeen studies including 3478 participants were included in this meta-analysis. The overall pooled sensitivity, specificity, PLR, NLR and DOR were 0.77 (95 % CI: 0.74-0.79), 0.74 (95 % CI: 0.72-0.75), 3.58 (95 % CI: 2.85-4.49), 0.29 (95 % CI: 0.22-0.37) and 15.18 (95 % CI: 9.75-23.62), respectively. In addition, the area under the SROC curve (AUC) was 0.8666, and no threshold effect was found based on the Spearman correlation analysis (P = 0.616). Besides, subgroup analysis showed higher sensitivity, specificity and AUC in term infants and proven infection group than those in preterm infants and clinical infection group, respectively. CONCLUSIONS: The n CD64 expression alone is not a satisfactory marker for diagnosing neonatal sepsis with relatively low sensitivity, specificity, PLR and NLR, in spite of relatively high SROC area. Therefore, the n CD64 expression used in diagnosis of neonatal sepsis should be treated with caution. PMID- 27268051 TI - Mapping Sites of O-Glycosylation and Fringe Elongation on Drosophila Notch. AB - Glycosylation of the Notch receptor is essential for its activity and serves as an important modulator of signaling. Three major forms of O-glycosylation are predicted to occur at consensus sites within the epidermal growth factor-like repeats in the extracellular domain of the receptor: O-fucosylation, O glucosylation, and O-GlcNAcylation. We have performed comprehensive mass spectral analyses of these three types of O-glycosylation on Drosophila Notch produced in S2 cells and identified peptides containing all 22 predicted O-fucose sites, all 18 predicted O-glucose sites, and all 18 putative O-GlcNAc sites. Using semiquantitative mass spectral methods, we have evaluated the occupancy and relative amounts of glycans at each site. The majority of the O-fucose sites were modified to high stoichiometries. Upon expression of the beta3-N acetylglucosaminyltransferase Fringe with Notch, we observed varying degrees of elongation beyond O-fucose monosaccharide, indicating that Fringe preferentially modifies certain sites more than others. Rumi modified O-glucose sites to high stoichiometries, although elongation of the O-glucose was site-specific. Although the current putative consensus sequence for O-GlcNAcylation predicts 18 O-GlcNAc sites on Notch, we only observed apparent O-GlcNAc modification at five sites. In addition, we performed mass spectral analysis on endogenous Notch purified from Drosophila embryos and found that the glycosylation states were similar to those found on Notch from S2 cells. These data provide foundational information for future studies investigating the mechanisms of how O-glycosylation regulates Notch activity. PMID- 27268043 TI - Medicinal plants--prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review. AB - BACKGROUND: Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves <= 35%; piglets <= 50%) and for respiratory diseases (calves <= 80%; piglets <= 40%). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs'. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. RESULTS: Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20'000 peer-reviewed articles published in the last 20 years (1994-2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. CONCLUSIONS: Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies. PMID- 27268052 TI - Synthetic Lethal Screen Demonstrates That a JAK2 Inhibitor Suppresses a BCL6 dependent IL10RA/JAK2/STAT3 Pathway in High Grade B-cell Lymphoma. AB - We demonstrate the usefulness of synthetic lethal screening of a conditionally BCL6-deficient Burkitt lymphoma cell line, DG75-AB7, with a library of small molecules to determine survival pathways suppressed by BCL6 and suggest mechanism based treatments for lymphoma. Lestaurtinib, a JAK2 inhibitor and one of the hits from the screen, repressed survival of BCL6-deficient cells in vitro and reduced growth and proliferation of xenografts in vivo BCL6 deficiency in DG75-AB7 induced JAK2 mRNA and protein expression and STAT3 phosphorylation. Surface IL10RA was elevated by BCL6 deficiency, and blockade of IL10RA repressed STAT3 phosphorylation. Therefore, we define an IL10RA/JAK2/STAT3 pathway each component of which is repressed by BCL6. We also show for the first time that JAK2 is a direct BCL6 target gene; BCL6 bound to the JAK2 promoter in vitro and was enriched by ChIP-seq. The place of JAK2 inhibitors in the treatment of diffuse large B-cell lymphoma has not been defined; we suggest that JAK2 inhibitors might be most effective in poor prognosis ABC-DLBCL, which shows higher levels of IL10RA, JAK2, and STAT3 but lower levels of BCL6 than GC-DLBCL and might be usefully combined with novel approaches such as inhibition of IL10RA. PMID- 27268053 TI - The Baseplate of Lactobacillus delbrueckii Bacteriophage Ld17 Harbors a Glycerophosphodiesterase. AB - Glycerophosphodiester phosphodiesterases (GDPDs; EC 3.1.4.46) typically hydrolyze glycerophosphodiesters to sn-glycerol 3-phosphate (Gro3P) and their corresponding alcohol during patho/physiological processes in bacteria and eukaryotes. GDPD( like) domains were identified in the structural particle of bacterial viruses (bacteriophages) specifically infecting Gram-positive bacteria. The GDPD of phage 17 (Ld17; GDPDLd17), representative of the group b Lactobacillus delbrueckii subsp. bulgaricus (Ldb)-infecting bacteriophages, was shown to hydrolyze, besides the simple glycerophosphodiester, two complex surface-associated carbohydrates of the Ldb17 cell envelope: the Gro3P decoration of the major surface polysaccharide d-galactan and the oligo(glycerol phosphate) backbone of the partially glycosylated cell wall teichoic acid, a minor Ldb17 cell envelope component. Degradation of cell wall teichoic acid occurs according to an exolytic mechanism, and Gro3P substitution is presumed to be inhibitory for GDPDLd17 activity. The presence of the GDPDLd17 homotrimer in the viral baseplate structure involved in phage-host interaction together with the dependence of native GDPD activity, adsorption, and efficiency of plating of Ca(2+) ions supports a role for GDPDLd17 activity during phage adsorption and/or phage genome injection. In contrast to GDPDLd17, we could not identify any enzymatic activity for the GDPD-like domain in the neck passage structure of phage 340, a 936-type Lactococcus lactis subsp. lactis bacteriophage. PMID- 27268054 TI - RNA-seq Analysis of delta9-Tetrahydrocannabinol-treated T Cells Reveals Altered Gene Expression Profiles That Regulate Immune Response and Cell Proliferation. AB - Marijuana has drawn significant public attention and concern both for its medicinal and recreational use. Delta9-Tetrahydrocannabinol (THC), which is the main bioactive component in marijuana, has also been shown to possess potent anti inflammatory properties by virtue of its ability to activate cannabinoid receptor 2 (CB-2) expressed on immune cells. In this study, we used RNA-seq to quantify the transcriptomes and transcript variants that are differentially regulated by THC in super antigen-activated lymph node cells and CD4(+) T cells. We found that the expressions of many transcripts were altered by THC in both total lymph node cells and CD4(+) T cells. Furthermore, the abundance of many miRNA precursors and long non-coding RNAs was dramatically altered in THC-treated mice. For example, the expression of miR-17/92 cluster and miR-374b/421 cluster was down-regulated by THC. On the other hand miR-146a, which has been shown to induce apoptosis, was up-regulated by THC. Long non-coding RNAs that are expressed from the opposite strand of CD27 and Appbp2 were induced by THC. In addition, THC treatment also caused alternative promoter usage and splicing. The functions of those altered transcripts were mainly related to immune response and cell proliferation. PMID- 27268055 TI - Light and pH-induced Changes in Structure and Accessibility of Transmembrane Helix B and Its Immediate Environment in Channelrhodopsin-2. AB - A variant of the cation channel channelrhodopsin-2 from Chlamydomonas reinhardtii (CrChR2) was selectively labeled at position Cys-79 at the end of the first cytoplasmic loop and the beginning of transmembrane helix B with the fluorescent dye fluorescein (acetamidofluorescein). We utilized (i) time-resolved fluorescence anisotropy experiments to monitor the structural dynamics at the cytoplasmic surface close to the inner gate in the dark and after illumination in the open channel state and (ii) time-resolved fluorescence quenching experiments to observe the solvent accessibility of helix B at pH 6.0 and 7.4. The light induced increase in final anisotropy for acetamidofluorescein bound to the channel variant with a prolonged conducting state clearly shows that the formation of the open channel state is associated with a large conformational change at the cytoplasmic surface, consistent with an outward tilt of helix B. Furthermore, results from solute accessibility studies of the cytoplasmic end of helix B suggest a pH-dependent structural heterogeneity that appears below pH 7. At pH 7.4 conformational homogeneity was observed, whereas at pH 6.0 two protein fractions exist, including one in which residue 79 is buried. This inaccessible fraction amounts to 66% in nanodiscs and 82% in micelles. Knowledge about pH dependent structural heterogeneity may be important for CrChR2 applications in optogenetics. PMID- 27268056 TI - Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2. AB - We show that a peptide from Chikungunya virus nsP3 protein spanning residues 1728 1744 binds the amphiphysin-2 (BIN1) Src homology-3 (SH3) domain with an unusually high affinity (Kd 24 nm). Our NMR solution complex structure together with isothermal titration calorimetry data on several related viral and cellular peptide ligands reveal that this exceptional affinity originates from interactions between multiple basic residues in the target peptide and the extensive negatively charged binding surface of amphiphysin-2 SH3. Remarkably, these arginines show no fixed conformation in the complex structure, indicating that a transient or fluctuating polyelectrostatic interaction accounts for this affinity. Thus, via optimization of such dynamic electrostatic forces, viral peptides have evolved a superior binding affinity for amphiphysin-2 SH3 compared with typical cellular ligands, such as dynamin, thereby enabling hijacking of amphiphysin-2 SH3-regulated host cell processes by these viruses. Moreover, our data show that the previously described consensus sequence PXRPXR for amphiphysin SH3 ligands is inaccurate and instead define it as an extended Class II binding motif PXXPXRpXR, where additional positive charges between the two constant arginine residues can give rise to extraordinary high SH3 binding affinity. PMID- 27268057 TI - Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin. AB - Remodeling of the acyl chains of cardiolipin (CL) is responsible for final molecular composition of mature CL after de novo CL synthesis in mitochondria. Yeast Saccharomyces cerevisiae undergoes tafazzin-mediated CL remodeling, in which tafazzin serves as a transacylase from phospholipids to monolyso-CL (MLCL). In light of the diversity of the acyl compositions of mature CL between different organisms, the mechanism underlying tafazzin-mediated transacylation remains to be elucidated. We investigated the mechanism responsible for transacylation using purified S. cerevisiae tafazzin with liposomes composed of various sets of acyl donors and acceptors. The results revealed that tafazzin efficiently catalyzes transacylation in liposomal membranes with highly ordered lipid bilayer structure. Tafazzin elicited unique acyl chain specificity against phosphatidylcholine (PC) as follows: linoleoyl (18:2) > oleoyl (18:1) = palmitoleoyl (16:1) ? palmitoyl (16:0). In these reactions, tafazzin selectively removed the sn-2 acyl chain of PC and transferred it into the sn-1 and sn-2 positions of MLCL isomers at equivalent rates. We demonstrated for the first time that MLCL and dilyso-CL have inherent abilities to function as an acyl donor to monolyso-PC and acyl acceptor from PC, respectively. Furthermore, a Barth syndrome-associated tafazzin mutant (H77Q) was shown to completely lack the catalytic activity in our assay. It is difficult to reconcile the present results with the so-called thermodynamic remodeling hypothesis, which premises that tafazzin reacylates MLCL by unsaturated acyl chains only in disordered non bilayer lipid domain. The acyl specificity of tafazzin may be one of the factors that determine the acyl composition of mature CL in S. cerevisiae mitochondria. PMID- 27268058 TI - OxyR2 Functions as a Three-state Redox Switch to Tightly Regulate Production of Prx2, a Peroxiredoxin of Vibrio vulnificus. AB - The bacterial transcriptional regulator OxyR is known to function as a two-state redox switch. OxyR senses cellular levels of H2O2 via a "sensing cysteine" that switches from the reduced to a disulfide state upon H2O2 exposure, inducing the expression of antioxidant genes. The reduced and disulfide states of OxyR, respectively, bind to extended and compact regions of DNA, where the reduced state blocks and the oxidized state allows transcription and further induces target gene expression by interacting with RNA polymerase. Vibrio vulnificus OxyR2 senses H2O2 with high sensitivity and induces the gene encoding the antioxidant Prx2. In this study, we used mass spectrometry to identify a third redox state of OxyR2, in which the sensing cysteine was overoxidized to S sulfonated cysteine (Cys-SO3H) by high H2O2 in vitro and in vivo, where the modification deterred the transcription of prx2 The DNA binding preferences of OxyR25CA-C206D, which mimics overoxidized OxyR2, suggested that overoxidized OxyR2 binds to the extended DNA site, masking the -35 region of the prx2 promoter. These combined results demonstrate that OxyR2 functions as a three state redox switch to tightly regulate the expression of prx2, preventing futile production of Prx2 in cells exposed to high levels of H2O2 sufficient to inactivate Prx2. We further provide evidence that another OxyR homolog, OxyR1, displays similar three-state behavior, inviting further exploration of this phenomenon as a potentially general regulatory mechanism. PMID- 27268059 TI - Negligible risk of inducing resistance in Mycobacterium tuberculosis with single dose rifampicin as post-exposure prophylaxis for leprosy. AB - Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis. PMID- 27268061 TI - Strategies for disseminating recommendations or guidelines to patients: a systematic review. AB - BACKGROUND: The aim of this systematic literature review was to assess what dissemination strategies are feasible to inform and educate patients about recommendations (also known as guidelines). METHODS: The search was performed in February 2016 in PubMed, Ebsco/PsycINFO, Ebsco/CINAHL and Embase. Studies evaluating dissemination strategies, involving patients and/or reaching patients, were included. A hand search and a search in the grey literature, also done in February 2016, were added. Searches were not restricted by language or publication type. Publications that referred to (1) guideline(s) or recommendation(s), (2) dissemination, (3) dissemination with patients/patient organisations and (4) dissemination to patients/patient organisations were included in this article. Criteria 1 AND 2 were mandatory together with criteria 3 OR 4. RESULTS: The initial search revealed 3753 unique publications. Forty seven articles met the inclusion criteria and were selected for detailed review. The hand search and grey literature resulted in four relevant articles. After reading the full text of the 47 articles, 21 were relevant for answering our research question. Most publications had low levels of evidence, 3 or 4 of the Oxford levels of evidence. One article had a level of evidence of 2(b). This article gives an overview of tools and strategies to disseminate recommendations to patients. Key factors of success were a dissemination plan, written at the start of the recommendation development process, involvement of patients in this development process and the use of a combination of traditional and innovative dissemination tools. The lack of strong evidence calls for more research of the effectiveness of different dissemination strategies as well as the barriers for implementing a strategic approach of dissemination. CONCLUSION: Our findings provide the first systematic overview of tools and strategies to disseminate recommendations to patients and patient organisations. Participation of patients in the whole process is one of the most important findings. These findings are relevant to develop, implement and evaluate more (effective) dissemination strategies which can improve health care. PMID- 27268060 TI - Oxytocin and cardioprotection in diabetes and obesity. AB - Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs. PMID- 27268062 TI - Diffusion-weighted and dynamic contrast-enhanced MRI of pancreatic adenocarcinoma xenografts: associations with tumor differentiation and collagen content. AB - PURPOSE: The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the level of differentiation and the composition of the stroma. In this preclinical study, we investigated the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as noninvasive methods for providing information on the differentiation and the stroma of PDACs. METHODS: Xenografted tumors initiated from four PDAC cell lines (BxPC-3, Capan-2, MIAPaCa-2, and Panc-1) were included in the study. DW-MRI and DCE-MRI were carried out on a 7.05-T MR scanner, and tumor images of ADC (the apparent diffusion coefficient), K (trans) (the volume transfer constant of Gd-DOTA), and v e (the fractional distribution volume of Gd-DOTA) were produced. The level of differentiation and the amount and structure of collagen I and collagen IV were determined by examining histological preparations. RESULTS: Differentiated tumors showed lower levels of collagen I and collagen IV than non-differentiated tumors. Significant correlations were found between ADC and v e, and both parameters differentiated clearly between collagen-rich non-differentiated tumors and differentiated tumors containing less collagen. CONCLUSION: Differentiated PDAC xenografts show higher ADC values and higher v e values than their non-differentiated counterparts. This observation supports the application of parametric MR images as tumor biomarkers in PDAC. Patients showing low values of ADC and v e most likely have non-differentiated tumors with extensive stroma and, hence, poor prognosis. PMID- 27268063 TI - Electronic nicotine delivery system dual use and intention to quit smoking: Will the socioeconomic gap in smoking get greater? AB - INTRODUCTION: Electronic nicotine delivery systems (ENDS) are popular among cigarette smokers; however, it is not known whether the use of ENDS assists or delays quitting cigarettes, especially among certain priority populations. We examined predictors of intention to quit smoking and patterns of dual use of ENDS and traditional cigarettes among priority populations. METHODS: This study used data from a 2014 survey of a national probability sample of 5717 USA adults. Descriptive statistics were used to examine differences in intention to quit cigarette use among current cigarette smokers (n=1014) and dual users of cigarettes and ENDS (n=248). Multivariable logistic regression analysis was conducted on the overall sample and the subsample of dual users to determine whether dual use (versus cigarette only use) and demographic characteristics predict self-reported intention to quit and having attempted to quit in the past year. Significance was set at p<0.05. RESULTS: Compared to cigarette smokers, dual users were slightly more educated (p<0.05), more likely to intend to quit smoking (adjusted odds ratio [AOR]=1.8, p=0.001), and more likely to have attempted to quit smoking in the past year (AOR=1.7, p=0.003). Blacks reported higher intention to quit than Whites (AOR=1.8, p=0.003). Compared with high school education or less, dual users with some college (AOR=1.5, p=0.007) or a college degree (AOR=2.5, p<=0.0001) had high intention to quit. CONCLUSIONS: Dual users of ENDS and traditional cigarettes are more likely to intend to quit smoking and have recently made quit attempts. If using ENDS contributes to increased smoking cessation among more educated individuals, disparity in smoking by level of education will increase. PMID- 27268064 TI - Multilayer Approach for Advanced Hybrid Lithium Battery. AB - Conventional intercalated rechargeable batteries have shown their capacity limit, and the development of an alternative battery system with higher capacity is strongly needed for sustainable electrical vehicles and hand-held devices. Herein, we introduce a feasible and scalable multilayer approach to fabricate a promising hybrid lithium battery with superior capacity and multivoltage plateaus. A sulfur-rich electrode (90 wt % S) is covered by a dual layer of graphite/Li4Ti5O12, where the active materials S and Li4Ti5O12 can both take part in redox reactions and thus deliver a high capacity of 572 mAh gcathode(-1) (vs the total mass of electrode) or 1866 mAh gs(-1) (vs the mass of sulfur) at 0.1C (with the definition of 1C = 1675 mA gs(-1)). The battery shows unique voltage platforms at 2.35 and 2.1 V, contributed from S, and 1.55 V from Li4Ti5O12. A high rate capability of 566 mAh gcathode(-1) at 0.25C and 376 mAh gcathode(-1) at 1C with durable cycle ability over 100 cycles can be achieved. Operando Raman and electron microscope analysis confirm that the graphite/Li4Ti5O12 layer slows the dissolution/migration of polysulfides, thereby giving rise to a higher sulfur utilization and a slower capacity decay. This advanced hybrid battery with a multilayer concept for marrying different voltage plateaus from various electrode materials opens a way of providing tunable capacity and multiple voltage platforms for energy device applications. PMID- 27268065 TI - First case of herpetic meningoencephalitis treated with ganciclovir. AB - Consensus treatment for herpetic meningoencephalitis is intravenous aciclovir but no guidelines are available for alternative treatment in case of renal failure induced by aciclovir. We report to the best of our knowledge, the first case of herpetic meningoencephalitis treated with success by ganciclovir. PMID- 27268066 TI - Individual, social and community-level predictors of wellbeing in a US sample of transgender and gender non-conforming individuals. AB - In the last decade, increased attention has been paid to the physical and mental health needs of transgender and gender non-conforming individuals. However, despite this surge of research, scant literature addresses factors associated with wellbeing among members of this population. Using data from the US Social Justice Sexuality Survey, this study examines predictors of wellbeing in a sample of transgender and gender non-conforming individuals. Results indicate that higher levels of wellbeing are predicted by education, older age and a greater sense of connectedness to the lesbian, gay, bisexual and transgender community. Additionally, although health insurance did not have a significant impact on wellbeing, increased general health was associated with greater wellbeing, as was perceived comfort of the healthcare provider regarding the respondent's sexual identity. These findings can inform multi-level intervention with transgender and gender non-conforming persons to promote their wellbeing, as well as guide policies and practices around healthcare provider training. Future research should further examine the interconnected predictors of wellbeing among members of this population. PMID- 27268067 TI - Dissemination of visceral leishmaniasis to Western Argentina: When will imported canine vector-borne zoonotic diseases start being local? PMID- 27268068 TI - Results of a phase II study of thalidomide and azacitidine in patients with clinically advanced myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and low blast count acute myeloid leukemia (AML). AB - Single agent azacitidine or immunomodulatory drugs are effective in myelodysplastic syndrome (MDS), with differing target mechanisms and toxicities. Objectives of this ALLG MDS3 study in clinically advanced MDS, AMML and low blast AML were to establish safety, response and quality of life of azacitidine and thalidomide. Patients received azacitidine (75mg/m2/d sc 7days every 28 days), and oral thalidomide up to 100mg/d for maximum 12months. Eighty patients registered; median age 68 years (range 42-82), 49% IPSS int2-high. With 36.5 months follow up, patients received median 9 cycles azacitidine, 6.1mths thalidomide. Nonhematologic toxicity grade 3+ in 85%, commonly infections. Overall response rate was 63%; 26% CR were unaffected by IPSS. Median response duration 26.3months; overall survival was 28.1months. This combination azacitidine and thalidomide in clinically advanced MDS, CMML and low-blast AML was tolerable without unexpected toxicity and encouraging responses support further investigation of combination approaches with hypomethylating agent and immunomodulatory drug. PMID- 27268069 TI - Does 1-Allyl-3-methylimidazolium chloride Act as a Biocompatible Solvent for Stem Bromelain? AB - The broader scope of ILs in chemical sciences particularly in pharmaceutical, bioanalytical and many more applications is increasing day by day. Hitherto, a very less amount of research is available in the depiction of conformational stability, activity, and thermal stability of enzymes in the presence of ILs. In the present study, the perturbation in the structure, stability, and activity of stem bromelain (BM) has been observed in the presence of 1-allyl-3 methylimidazolium chloride ([Amim][Cl]) using various techniques. This is the first report in which the influence of [Amim][Cl] has been studied on the enzyme BM. Fluorescence spectroscopy has been utilized to map out the changes in the environment around tryptophan (Trp) residues of BM and also to discuss the variations in the thermal stability of BM as an outcome of its interaction with the IL at different concentrations. Further, the work delineates the denaturing effect of high concentration of IL on enzyme structure and activity. It dictates the fact that low concentrations (0.01-0.10 M) of [Amim][Cl] are only changing the structural arrangement of the protein without having harsh consequences on its activity and stability. However, high concentrations of IL proved to be totally devastating for both activity and stability of BM. The observed decrease in the stability of BM at high concentration may be due to the combined effect of cation and anion interactions with the protein residues. The present work is successful in dictating the probable mechanism of interaction between BM and [Amim][Cl]. These results can prove to be fruitful in the studies of enzymes in aqueous IL systems since the used IL is thermally stable and nonvolatile in nature thereby providing a pathway of alteration in the activity of enzymes in potentially green systems. PMID- 27268070 TI - Evaluation of three force-position hybrid control methods for a robot-based biological joint-testing system. AB - BACKGROUND: Robot-based joint-testing systems (RJTS) can be used to perform unconstrained laxity tests, measuring the stiffness of a degree of freedom (DOF) of the joint at a fixed flexion angle while allowing the other DOFs unconstrained movement. Previous studies using the force-position hybrid (FPH) control method proposed by Fujie et al. (J Biomech Eng 115(3):211-7, 1993) focused on anterior/posterior tests. Its convergence and applicability on other clinically relevant DOFs such as valgus/varus have not been demonstrated. The current s1tudy aimed to develop a 6-DOF RJTS using an industrial robot, to propose two new force position hybrid control methods, and to evaluate the performance of the methods and FPH in controlling the RJTS for anterior/posterior and valgus/varus laxity tests of the knee joint. METHODS: An RJTS was developed using an industrial 6-DOF robot with a 6-component load-cell attached at the effector. The performances of FPH and two new control methods, namely force-position alternate control (FPA) and force-position hybrid control with force-moment control (FPHFM), for unconstrained anterior/posterior and valgus/varus laxity tests were evaluated and compared with traditional constrained tests (CT) in terms of the number of control iterations, total time and the constraining forces and moments. RESULTS: As opposed to CT, the other three control methods successfully reduced the constraining forces and moments for both anterior/posterior and valgus/varus tests, FPHFM being the best followed in order by FPA and FPH. FPHFM had root-mean squared constraining forces and moments of less than 2.2 N and 0.09 Nm, respectively at 0 degrees flexion, and 2.3 N and 0.14 Nm at 30 degrees flexion. The corresponding values for FPH were 8.5 N and 0.33 Nm, and 11.5 N and 0.45 Nm, respectively. Given the same control parameters including the compliance matrix, FPHFM and FPA reduced the constraining loads of FPH at the expense of additional control iterations, and thus increased total time, FPA taking about 10 % longer than FPHFM. CONCLUSIONS: The FPHFM would be the best choice among the methods considered when longer total time is acceptable in the intended clinical applications. The current results will be useful for selecting a force-position hybrid control method for unconstrained laxity tests using an RJTS. PMID- 27268071 TI - Research into "real world" older patients is needed. PMID- 27268072 TI - Effects of heat acclimation on hand cooling efficacy following exercise in the heat. AB - This study examined the separate and combined effects of heat acclimation and hand cooling on post-exercise cooling rates following bouts of exercise in the heat. Seventeen non-heat acclimated (NHA) males (mean +/- SE; age, 23 +/- 1 y; mass, 75.30 +/- 2.27 kg; maximal oxygen consumption [VO2 max], 54.1 +/- 1.3 ml.kg 1.min-1) completed 2 heat stress tests (HST) when NHA, then 10 days of heat acclimation, then 2 HST once heat acclimated (HA) in an environmental chamber (40 degrees C; 40%RH). HSTs were 2 60-min bouts of treadmill exercise (45% VO2 max; 2% grade) each followed by 10 min of hand cooling (C) or no cooling (NC). Heat acclimation sessions were 90-240 min of treadmill or stationary bike exercise (60 80% VO2 max). Repeated measures ANOVA with Fishers LSD post hoc (alpha < 0.05) identified differences. When NHA, C (0.020 +/- 0.003 degrees C.min-1) had a greater cooling rate than NC (0.013 +/- 0.003 degrees C.min-1) (mean difference [95%CI]; 0.007 degrees C [0.001,0.013], P = 0.035). Once HA, C (0.021 +/- 0.002 degrees C.min-1) was similar to NC (0.025 +/- 0.002 degrees C.min-1) (0.004 degrees C [-0.003,0.011], P = 0.216). Hand cooling when HA (0.021 +/- 0.002 degrees C.min-1) was similar to when NHA (0.020 +/- 0.003 degrees C.min-1) (P = 0.77). In conclusion, when NHA, C provided greater cooling rates than NC. Once HA, C and NC provided similar cooling rates. PMID- 27268073 TI - Diterpenoid alkaloids from the roots of Aconitum brachypodum Diels. AB - A new diterpenoid alkaloid, named bullatine H (1), along with 10 known diterpenoid alkaloids were isolated from the roots of Aconitum brachypodum Diels (Ranunculaceae). The structure of 1 was elucidated by analysis of its spectroscopic data. It should be noted that compound 1 is the first example with 11, 13-dioxygenated denudatine-type diterpenoid alkaloid isolated from Aconitum brachypodum. PMID- 27268075 TI - Double strand breaks may be a missing link between entropy and aging. AB - It has been previously suggested that an increase in entropy production leads to aging. However, the mechanisms linking increased entropy production in living mass to aging are currently unclear. Even though entropy cannot be easily associated with any specific molecular damage, the increase of entropy in structural mass may be connected with heat stress, which is known to generate double strand breaks. Double strand breaks, which are in turn known to play an important role in process of aging, are thus connected to both aging and an increase of entropy. In view of these associations, we propose a new model where the increase of entropy leads to the formation of double strand breaks, resulting in an aging phenotype. This not only offers a new perspective on aging research and facilitates experimental validation, but could also serve as a useful explanatory tool. PMID- 27268076 TI - Formation of the inner ear during embryonic and larval development of the cichlid fish (Oreochromis mossambicus). AB - BACKGROUND: The vertebrate inner ear comprises mineralized elements, namely the otoliths (fishes) or the otoconia (mammals). These elements serve vestibular and auditory functions. The formation of otoconia and otoliths is described as a stepwise process, and in fish, it is generally divided into an aggregation of the otolith primordia from precursor particles and then a growth process that continues throughout life. RESULTS: This study was undertaken to investigate the complex transition between these two steps. Therefore, we investigated the developmental profiles of several inner ear structural and calcium-binding proteins during the complete embryonic and larval development of the cichlid fish Oreochromis mossambicus in parallel with the morphology of inner ear and especially otoliths. We show that the formation of otoliths is a highly regulated temporal and spatial process which takes place throughout embryonic and larval development. CONCLUSIONS: Based on our data we defined eight phases of otolith differentiation from the primordia to the mature otolith. PMID- 27268074 TI - Does cytomegalovirus infection contribute to socioeconomic disparities in all cause mortality? AB - The social patterning of cytomegalovirus (CMV) and its implication in aging suggest that the virus may partially contribute to socioeconomic disparities in mortality. We used Cox regression and inverse odds ratio weighting to quantify the proportion of the association between socioeconomic status (SES) and all cause mortality that was attributable to mediation by CMV seropositivity. Data were from the National Health and Nutrition Examination Survey (NHANES) III (1988 1994), with mortality follow-up through December 2011. SES was assessed as household income (income-to-poverty ratio <=1.30;>1.30 to<=1.85;>1.85 to<=3.50;>3.50) and education (high school). We found strong associations between low SES and increased mortality: hazard ratio (HR) 1.80; 95% confidence interval (CI): 1.57, 2.06 comparing the lowest versus highest income groups and HR 1.29; 95% CI: 1.13, 1.48 comparing high school education. 65% of individuals were CMV seropositive, accounting for 6-15% of the SES-mortality associations. Age modified the associations between SES, CMV, and mortality, with CMV more strongly associated with mortality in older individuals. Our findings suggest that cytomegalovirus may partially contribute to persistent socioeconomic disparities in mortality, particularly among older individuals. PMID- 27268077 TI - Synthesis and Characterization of Biodegradable Lignin Nanoparticles with Tunable Surface Properties. AB - Lignin nanoparticles can serve as biodegradable carriers of biocidal actives with minimal environmental footprint. Here we describe the colloidal synthesis and interfacial design of nanoparticles with tunable surface properties using two different lignin precursors, Kraft (Indulin AT) lignin and Organosolv (high purity lignin). The green synthesis process is based on flash precipitation of dissolved lignin polymer, which enabled the formation of nanoparticles in the size range of 45-250 nm. The size evolution of the two types of lignin particles is fitted on the basis of modified diffusive growth kinetics and mass balance dependencies. The surface properties of the nanoparticles are fine-tuned by coating them with a cationic polyelectrolyte, poly(diallyldimethylammonium chloride). We analyze how the colloidal stability and dispersion properties of these two types of nanoparticles vary as a function of pH and salinities. The data show that the properties of the nanoparticles are governed by the type of lignin used and the presence of polyelectrolyte surface coating. The coating allows the control of the nanoparticles' surface charge and the extension of their stability into strongly basic regimes, facilitating their potential application at extreme pH conditions. PMID- 27268080 TI - Chrysanthemum morifolium extract improves hypertension-induced cardiac hypertrophy in rats by reduction of blood pressure and inhibition of myocardial hypoxia inducible factor-1alpha expression. AB - CONTEXT: Chrysanthemum morifolium Ramat. (Asteraceae) extract (CME) possesses a vasodilator effect in vitro. However, the use of polyphenol-rich CME in the treatment of hypertension-induced cardiac hypertrophy has not been reported. OBJECTIVE: We investigated the effect of polyphenol-rich CME on hypertension induced cardiac hypertrophy in rats and its possible mechanism of action. MATERIALS AND METHODS: The Sprague-Dawley rat model with cardiac hypertrophy was induced by renovascular hypertension. The blood pressure, cardiac weight index, free fatty acids (FFA) in serum and myocardium, and protein expressions of myocardial hypoxia inducible factor-1alpha (HIF-1alpha), peroxisome proliferator activated receptor alpha (PPARalpha), carnitine palmitoyltransferase-1a (CPT-1a), pyruvate dehydrogenase kinase-4 (PDK-4) and glucose transporter-4 (GLUT-4) were measured after treating hypertensive rats with polyphenol-rich CME of anthodia 75 150 mg/kg once daily for 4 weeks. A myocardial histological examination was also conducted. RESULTS: After CME treatment, the blood pressure, cardiac weight and cardiac weight index decreased by 5.7-9.6%, 9.2-18.4% and 10.9-20.1%, respectively, and the cardiomyocyte cross-sectional area also decreased by 8.3 30.4%. The CME treatment simultaneously decreased the FFA in serum and myocardium and protein expressions of myocardial HIF-1alpha and GLUT-4, and increased the protein expressions of myocardial PPARalpha, CPT-1a and PDK-4, especially in the CME 150 mg/kg group (p < 0.05 or p < 0.01). DISCUSSION AND CONCLUSION: Polyphenol rich CME may alleviate hypertensive cardiac hypertrophy in rats. Its mechanisms may be related to the reduction of blood pressure and amelioration of the myocardial energy metabolism. The latter may be attributed to the inhibition of HIF-1alpha expression and subsequent modulation of PPARalpha-mediated CPT-1a, PDK 4 and GLUT-4 expressions. PMID- 27268079 TI - Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer. AB - BACKGROUND: It has been shown that epidermal growth factor receptor (EGFR) mutation status is associated with 5-fluorouracil (5-FU) sensitivity in non-small cell lung cancer (NSCLC). However, the relationship between EGFR mutation status and dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, is unknown. METHODS: We elucidated the crosstalk among the EGFR signal cascade, the DPD gene (DPYD), and DPD protein expression via the transcription factor Sp1 and the effect of EGFR mutation status on the crosstalk. RESULTS: In the PC9 (exon19 E746 A750) study, EGF treatment induced up-regulation of both Sp1 and DPD; gefitinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI), and mithramycin A, a specific Sp-1 inhibitor, suppressed them. Among EGFR-mutated (PC9, HCC827; exon19 E746-A750 and H1975; exon21 L858R, T790M, gefitinib resistant) and -non-mutated (H1437, H1299) cell lines, EGF administration increased DPYD mRNA expression only in mutated cells (p < 0.05). Accordingly, gefitinib inhibited DPD protein expression only in PC9 and HCC827 cells, and mithramycin A inhibited it in EGFR-mutated cell lines, but not in wild-type. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line. CONCLUSIONS: The EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status. PMID- 27268078 TI - Phoenixin Activates Immortalized GnRH and Kisspeptin Neurons Through the Novel Receptor GPR173. AB - Reproductive function is coordinated by kisspeptin (Kiss) and GnRH neurons. Phoenixin-20 amide (PNX) is a recently described peptide found to increase GnRH stimulated LH secretion in the pituitary. However, the effects of PNX in the hypothalamus, the putative signaling pathways, and PNX receptor have yet to be identified. The mHypoA-GnRH/GFP and mHypoA-Kiss/GFP-3 cell lines represent populations of GnRH and Kiss neurons, respectively. PNX increased GnRH and GnRH receptor (GnRH-R) mRNA expression, as well as GnRH secretion, in the mHypoA GnRH/GFP cell model. In the mHypoA-Kiss/GFP-3 cell line, PNX increased Kiss1 mRNA expression. CCAAT/enhancer-binding protein (C/EBP)-beta, octamer transcription factor-1 (Oct-1), and cAMP response element binding protein (CREB) binding sites are localized to the 5' flanking regions of the GnRH, GnRH-R, and Kiss1 genes. PNX decreased C/EBP-beta mRNA expression in both cell models and increased Oct-1 mRNA expression in the mHypoA-GnRH/GFP neurons. PNX increased CREB phosphorylation in both cell models and phospho-ERK1/2 in the mHypoA-GnRH/GFP cell model, whereas inhibiting the cAMP/protein kinase A pathway prevented PNX induction of GnRH and Kiss1 mRNA expression. Importantly, we determined that the G protein-coupled receptor, GPR173, was strongly expressed in both GnRH and kisspeptin cell models and small interfering RNA knockdown of GPR173 prevented the PNX-mediated up-regulation of GnRH, GnRH-R, and Kiss1 mRNA expression and the down-regulation of C/EBP-beta mRNA expression. PNX also increased GPR173 mRNA expression in the mHypoA-GnRH/GFP cells. Taken together, these studies are the first to implicate that PNX acts through GPR173 to activate the cAMP/protein kinase A pathway through CREB, and potentially C/EBP-beta and/or Oct-1 to increase GnRH, GnRH-R, and Kiss1 gene expression, ultimately having a stimulatory effect on reproductive function. PMID- 27268081 TI - Distribution, Fate, Inhalation Exposure and Lung Cancer Risk of Atmospheric Polycyclic Aromatic Hydrocarbons in Some Asian Countries. AB - A large-scale monitoring program, the Asia Soil and Air Monitoring Program (Asia SAMP), was conducted in five Asian countries, including China, Japan, South Korea, Vietnam, and India. Air samples were collected using passive air samplers with polyurethane foam disks over four consecutive 3-month periods from September 2012 to August 2013 to measure the seasonal concentrations of 47 polycyclic aromatic hydrocarbons (PAHs), including 21 parent and 26 alkylated PAHs, at 176 sites (11 background, 83 rural, and 82 urban). The annual concentrations of total 47 PAHs (?47PAHs) at all sites ranged from 6.29 to 688 ng/m(3) with median of 82.2 ng/m(3). Air concentrations of PAHs in China, Vietnam, and India were greater than those in Japan and South Korea. As expected, the air concentrations (ng/m(3)) were highest at urban sites (143 +/- 117) followed by rural (126 +/- 147) and background sites (22.4 +/- 11.4). Significant positive correlations were found between PAH concentrations and atmosphere aerosol optical depth. The average benzo(a)pyrene equivalent concentration (BaPeq) was 5.61 ng/m(3). It was estimated that the annual BaPeq concentrations at 78.8% of the sampling sites exceeded the WHO guideline level. The mean population attributable fraction (PAF) for lung cancer due to inhalation exposure to outdoor PAHs was on the order 8.80/00 (0.056-520/00) for China, 0.380/00 (0.007-3.20/00) for Japan, 0.850/00 (0.042-4.50/00) for South Korea, 7.50/00 (0.26-270/00) for Vietnam, and 3.20/00 (0.047-200/00) for India. We estimated a number of lifetime excess lung cancer cases caused by exposure to PAHs, which the concentrations ranging from 27.8 to 2200, 1.36 to 108, 2.45 to 194, 21.8 to 1730, and 9.10 to 720 per million people for China, Japan, South Korea, Vietnam, and India, respectively. Overall, the lung cancer risk in China and Vietnam were higher than that in Japan, South Korea, and India. PMID- 27268083 TI - Workplace Bullying Among Family Physicians: A Gender Focused Study. AB - BACKGROUND: Continuing gender disparities within the medical profession have raised concerns about the extent to which women physicians face an inhospitable work environment. The purpose of this study was to examine the types and frequency of workplace bullying reported by a national sample of family physicians employed in academic settings, as related to gender. MATERIAL AND METHODS: Data for this study were gathered as part of the Council of Academic Family Medicine (CAMF) Educational Research Alliance (CERA) omnibus electronic survey. Respondents completed questions addressing sociodemographic and practice characteristics, general experience with bullying, types of bullying, actions in response to bullying, and outcomes. A total of 1065 academic family physicians (male = 56.8%; female = 43.2%), mostly non-Hispanic white (84.2%) or Asian (5.3%) and between the ages 30 and 60 (58.7%) completed the CERA survey. RESULTS: One in 10 respondents acknowledged bullying someone in the workplace; 30% had been personally bullied in the workplace. CONCLUSIONS: Compared to men, female physicians were more likely to report being bullied overall and, specifically, to experience having their opinions ignored, lack of recognition for good work, feeling pressured not to claim rightful benefits, and being given unmanageable workloads. Despite some gender differences in actions taken, outcomes for each kind of action were the same for men and women. PMID- 27268082 TI - Metal artefact reduction for patients with metallic dental fillings in helical neck computed tomography: comparison of adaptive iterative dose reduction 3D (AIDR 3D), forward-projected model-based iterative reconstruction solution (FIRST) and AIDR 3D with single-energy metal artefact reduction (SEMAR). AB - OBJECTIVES: To compare the differences in metal artefact degree and the depiction of structures in helical neck CT, in patients with metallic dental fillings, among adaptive iterative dose reduction three dimensional (AIDR 3D), forward projected model-based iterative reconstruction solution (FIRST) and AIDR 3D with single-energy metal artefact reduction (SEMAR-A). METHODS: In this retrospective clinical study, 22 patients (males, 13; females, 9; mean age, 64.6 +/- 12.6 years) with metallic dental fillings who underwent contrast-enhanced helical CT involving the oropharyngeal region were included. Neck axial images were reconstructed with AIDR 3D, FIRST and SEMAR-A. Metal artefact degree and depiction of structures (the apex and root of the tongue, parapharyngeal space, superior portion of the internal jugular chain and parotid gland) were evaluated on a four-point scale by two radiologists. Placing regions of interest, standard deviations of the oral cavity and nuchal muscle (at the slice where no metal exists) were measured and metal artefact indices were calculated (the square root of the difference of the squares of them). RESULTS: In SEMAR-A, metal artefact was significantly reduced and depictions of all structures were significantly improved compared with those in FIRST and AIDR 3D (p <= 0.001, sign test). Metal artefact index for the oral cavity in AIDR 3D/FIRST/SEMAR-A was 572.0/477.7/88.4, and significant differences were seen between each reconstruction algorithm (p < 0.0001, Wilcoxon signed-rank test). CONCLUSIONS: SEMAR-A could provide images with lesser metal artefact and better depiction of structures than AIDR 3D and FIRST. PMID- 27268085 TI - Higher daunorubicin exposure benefits FLT3 mutated acute myeloid leukemia. PMID- 27268084 TI - Dimethyl fumarate restores apoptosis sensitivity and inhibits tumor growth and metastasis in CTCL by targeting NF-kappaB. AB - Despite intensive efforts in recent years, a curative therapy for cutaneous T cell lymphoma (CTCL) has not yet been developed. Therefore, the establishment of new therapeutic approaches with higher efficacy rates and milder side effects is strongly desired. A characteristic feature of the malignant T-cell population in CTCL is resistance toward cell death resulting from constitutive NF-kappaB activation. Therefore, NF-kappaB-dependent cell death resistance represents an interesting therapeutic target in CTCL because an NF-kappaB-directed therapy would leave bystander T cells widely unaffected. We investigated the effects of dimethyl fumarate (DMF) on CTCL cells in vitro and in vivo. DMF induced cell death in primary patient-derived CD4(+) cells and CTCL cell lines, but hardly in T cells from healthy donors. DMF-induced cell death was linked specifically to NF kappaB inhibition. To study the impact of DMF in vivo, we developed 2 CTCL xenograft mouse models with different cutaneous localizations of the T-cell infiltrate. DMF treatment delayed the growth of CTCL tumors and prevented formation of distant metastases. In addition, DMF induced increased cell death in primary CTCL tumors and in liver metastases. In summary, DMF treatment represents a remarkable therapeutic option in CTCL because it restores CTCL apoptosis in vitro and in preclinical models in vivo and prevents spreading of the disease to distant sites. DMF treatment is of particular promise in CTCL because DMF is already in successful clinical use in the treatment of psoriasis and multiple sclerosis allowing fast translation into clinical studies in CTCL. PMID- 27268086 TI - c-Myb acts in parallel and cooperatively with Cebp1 to regulate neutrophil maturation in zebrafish. AB - Neutrophils are the key effectors for generating innate immunity in response to pathogenic infection and tissue injury in vertebrates. Dysregulation of neutrophil development and function is known to associate with various human disorders. Yet, the genetic network that orchestrates lineage commitment, differentiation, and maturation of neutrophils remains incompletely defined. Here, we present an in vivo study to delineate the genetic program underlying neutrophil development during zebrafish embryonic myelopoiesis. We show that loss of c-Myb function has no effect on macrophages but severely impairs neutrophil terminal differentiation, resulting in the accumulation of neutrophils with unsegmented nuclei and scant granule. This neutrophilic defect, which resembles the neutrophil-specific granule deficiency (SGD) caused by the mutations in CCAAT/enhancer-binding protein epsilon (C/EBPepsilon) in humans, is attributed, at least in part, to the downregulation of the granule protein transcription. Likewise, genetic inactivation of Cebp1, the zebrafish functional homolog of mammalian C/EBPepsilon, also leads to a similar SGD-like phenotype in zebrafish. Genetic epistasis and biochemical analysis further reveals that c-Myb and Cebp1 act in parallel and cooperatively to control neutrophil differentiation by directly regulating granule protein gene transcription. Our study indicates that c-MYB is an intrinsic master regulator for neutrophil terminal differentiation and a potential target in SGD patients. PMID- 27268087 TI - Mutational hierarchies in myelodysplastic syndromes dynamically adapt and evolve upon therapy response and failure. AB - Clonal evolution is believed to be a main driver for progression of various types of cancer and implicated in facilitating resistance to drugs. However, the hierarchical organization of malignant clones in the hematopoiesis of myelodysplastic syndromes (MDS) and its impact on response to drug therapy remain poorly understood. Using high-throughput sequencing of patient and xenografted cells, we evaluated the intratumoral heterogeneity (n= 54) and reconstructed mutational trajectories (n = 39) in patients suffering from MDS (n = 52) and chronic myelomonocytic leukemia-1 (n = 2). We identified linear and also branching evolution paths and confirmed on a patient-specific level that somatic mutations in epigenetic regulators and RNA splicing genes frequently constitute isolated disease-initiating events. Using high-throughput exome- and/or deep sequencing, we analyzed 103 chronologically acquired samples from 22 patients covering a cumulative observation time of 75 years MDS disease progression. Our data revealed highly dynamic shaping of complex oligoclonal architectures, specifically upon treatment with lenalidomide and other drugs. Despite initial clinical response to treatment, patients' marrow persistently remained clonal with rapid outgrowth of founder-, sub-, or even fully independent clones, indicating an increased dynamic rate of clonal turnover. The emergence and disappearance of specific clones frequently correlated with changes of clinical parameters, highlighting their distinct and far-reaching functional properties. Intriguingly, increasingly complex mutational trajectories are frequently accompanied by clinical progression during the course of disease. These data substantiate a need for regular broad molecular monitoring to guide clinical treatment decisions in MDS. PMID- 27268088 TI - Therapeutic targeting of IL-7Ralpha signaling pathways in ALL treatment. AB - Increased understanding of pediatric acute lymphoblastic leukemia (ALL) pathobiology has led to dramatic improvements in patient survival. However, there is still a need to develop targeted therapies to enable reduced chemotherapy intensity and to treat relapsed patients. The interleukin-7 receptor alpha (IL 7Ralpha) signaling pathways are prime therapeutic targets because these pathways harbor genetic aberrations in both T-cell ALL and B-cell precursor ALL. Therapeutic targeting of the IL-7Ralpha signaling pathways may lead to improved outcomes in a subset of patients. PMID- 27268089 TI - Adult human megakaryocyte-erythroid progenitors are in the CD34+CD38mid fraction. AB - Bipotent megakaryocyte/erythroid progenitors (MEPs) give rise to progeny limited to the megakaryocyte (Mk) and erythroid (E) lineages. We developed a novel dual detection functional in vitro colony-forming unit (CFU) assay for single cells that differentiates down both the Mk and E lineages (CFU-Mk/E), which allowed development and validation of a novel purification strategy for the identification and quantitation of primary functional human MEPs from granulocyte colony-stimulating factor-mobilized peripheral blood and bone marrow. Applying this assay to fluorescence-activated cell sorter-sorted cell populations, we found that the Lin(-)CD34(+)CD38(mid)CD45RA(-)FLT3(-)MPL(+)CD36(-)CD41(-) population is much more highly enriched for bipotent MEPs than any previously reported subpopulations. We also developed purification strategies for primary human lineage-committed Mk and E progenitors identified as CFU-Mk and burst forming unit-E. Comparative expression analyses in MEP, MkP, and ErP populations revealed differential expression of MYB We tested whether alterations in MYB concentration affect the Mk-E fate decision at the single cell level in MEPs and found that short hairpin RNA-mediated MYB knockdown promoted commitment of MEPs to the Mk lineage, further defining its role in MEP lineage fate. There are numerous applications for these novel enrichment strategies, including facilitating mechanistic studies of MEP lineage commitment, improving approaches for in vitro expansion of Mk and E cells, and developing improved therapies for benign and malignant hematologic disease. PMID- 27268091 TI - Distribution of thyroid hormone and thyrotropin receptors in reproductive tissues of adult female rabbits. AB - PURPOSE: Thyroid dysfunctions are related to anovulation, miscarriages, and infertility in women and laboratory animals. Mechanisms associated with these effects are unknown, although indirect or direct actions of thyroid hormones and thyrotropin could be assumed. The present study aimed to identify the distribution of thyroid hormones (TRs) and thyrotropin (TSHR) receptors in reproductive organs of female rabbits. MATERIAL AND METHODS: Ovary of virgin and pregnant rabbits, as well as the oviduct, uterus, and vagina of virgin rabbits were excised, histologically processed, and cut. Slices from these organs were used for immunohistochemical studies for TRalpha1-2, TRbeta1, and TSHR. RESULTS: The presence of TRs and TSHR was found in the primordial, primary, secondary, tertiary, and Graafian follicles of virgin rabbits, as well as in the corpora lutea, corpora albicans, and wall of hemorrhagic cysts of pregnant rabbits. Oviductal regions (fimbria-infundibulum, ampulla, isthmus, and utero-tubal junction), uterus (endometrium and myometrium), and vagina (abdominal, pelvic, and perineal portions) of virgin rabbits showed anti-TRs and anti-TSHR immunoreactivity. Additionally, the distal urethra, paravaginal ganglia, levator ani and iliococcygeus muscles, dorsal nerve and body of the clitoris, perigenital skin, and prostate had TRs and TSHR. CONCLUSIONS: The wide presence of TRs and TSHR in female reproductive organs suggests varied effects of thyroid hormones and thyrotropin in reproduction. PMID- 27268090 TI - Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target. AB - The importance of glutamine (Gln) metabolism in multiple myeloma (MM) cells and its potential role as a therapeutic target are still unknown, although it has been reported that human myeloma cell lines (HMCLs) are highly sensitive to Gln depletion. In this study, we found that both HMCLs and primary bone marrow (BM) CD138(+) cells produced large amounts of ammonium in the presence of Gln. MM patients have lower BM plasma Gln with higher ammonium and glutamate than patients with indolent monoclonal gammopathies. Interestingly, HMCLs expressed glutaminase (GLS1) and were sensitive to its inhibition, whereas they exhibited negligible expression of glutamine synthetase (GS). High GLS1 and low GS expression were also observed in primary CD138(+) cells. Gln-free incubation or treatment with the glutaminolytic enzyme l-asparaginase depleted the cell contents of Gln, glutamate, and the anaplerotic substrate 2-oxoglutarate, inhibiting MM cell growth. Consistent with the dependence of MM cells on extracellular Gln, a gene expression profile analysis, on both proprietary and published datasets, showed an increased expression of the Gln transporters SNAT1, ASCT2, and LAT1 by CD138(+) cells across the progression of monoclonal gammopathies. Among these transporters, only ASCT2 inhibition in HMCLs caused a marked decrease in Gln uptake and a significant fall in cell growth. Consistently, stable ASCT2 downregulation by a lentiviral approach inhibited HMCL growth in vitro and in a murine model. In conclusion, MM cells strictly depend on extracellular Gln and show features of Gln addiction. Therefore, the inhibition of Gln uptake is a new attractive therapeutic strategy for MM. PMID- 27268093 TI - The 2015 ESPEN Sir David Cuthbertson lecture: Inflammation as the driving force of muscle wasting in cancer. AB - Alterations in amino acid protein metabolism are a key feature of the cancer cachexia syndrome. These changes -induced by both hormonal changes (that affect insulin sensitivity) and inflammatory mediators- are present in skeletal muscle influencing both, amino acid uptake and protein synthesis. In addition, skeletal muscle protein turnover is characterized by an exacerbated rate of protein degradation, promoted by an activation of different proteolytic systems that include the ubiquitin-proteasome and the autophagic-lysosomal pathways. Changes in the rate of myogenesis/apoptosis also determine skeletal muscle mass during cancer cachexia. Indeed, a decreased skeletal muscle regeneration capacity is observed together with an increased rate of cell death, resulting in muscle wasting. Mitochondrial dysfunction also results in changes in skeletal muscle metabolism and further contributes to the exacerbation of the cancer-wasting syndrome. Different inflammatory mediators -either released by the tumor or by healthy cells of the cancer patient- are responsible for the activation of these catabolic processes that take place in skeletal muscle. PMID- 27268092 TI - Pulmonary Manifestations of the Autoimmune Lymphoproliferative Syndrome. A Retrospective Study of a Unique Patient Cohort. AB - RATIONALE: Patients with autoimmune lymphoproliferative syndrome (ALPS), a disorder of impaired lymphocyte apoptosis, often undergo radiographic chest imaging to evaluate the presence and progression of lymphadenopathy. These images often lead to parenchymal and interstitial lung findings of unclear clinical significance. OBJECTIVES: To characterize the pulmonary findings associated with ALPS and to determine if lung abnormalities present on computed tomographic (CT) imaging of the chest correlate with infection or functional status. METHODS: Patients with lung abnormalities observed on chest CT scans were retrospectively identified from the largest known ALPS cohort. Lung computed tomography findings were characterized and correlated with medical records, bronchoalveolar lavage, biopsy, and lung function. MEASUREMENTS AND MAIN RESULTS: CT images of the chest were available for 234 (92%) of 255 of the patients with ALPS. Among patients with a chest CT scan, 18 (8%) had lung abnormalities on at least one CT scan. Fourteen (78%) of those 18 were classified as having ALPS with undetermined genetic defect. Most patients (n = 16 [89%]) with lung lesions were asymptomatic. However, two (11%) of them had associated dyspnea and/or desaturation on room air. Immunosuppressive treatment was administered for lung disease in nine (50%) cases, and all were followed for clinical outcomes. CONCLUSIONS: Patients with ALPS can develop chest radiographic findings with protean manifestations that may mimic pulmonary infection. Management of patients with ALPS with incidental lung lesions identified by CT imaging should be guided by clinical correlation. Symptomatic patients may benefit from chest CT imaging and lesion biopsy to exclude infection and guide administration of immunosuppressive therapy. PMID- 27268094 TI - Role of atopy in chronic rhinosinusitis with nasal polyps: does an atopic condition affect the severity and recurrence of disease? AB - BACKGROUND: The role of atopy in chronic rhinosinusitis is unclear: it is particularly controversial in chronic rhinosinusitis with nasal polyps. METHODS: A prospective study of 210 patients with chronic rhinosinusitis with nasal polyps was performed. Patient demographics, visual analogue scale scores, Lund-Kennedy endoscopy scores, Lund-Mackay computed tomography scores, serum total immunoglobulin E levels, serum eosinophil cationic protein (ECP) levels and Phadiatop test findings were analysed. RESULTS: There were no significant differences in age, sex, visual analogue scale score, Lund-Mackay computed tomography score, total serum immunoglobulin E level, serum ECP level or Phadiatop test results between patients with primary and recurrent chronic rhinosinusitis with nasal polyps. A total of 99 patients (47 per cent) had positive atopy tests. No significant differences in sex, visual analogue scale score, Lund-Kennedy endoscopy score, Lund-Mackay computed tomography score or recurrence rates were found between atopic and non-atopic patients; however, atopic patients were significantly younger than non-atopic patients. Atopy status did not correlate with disease severity. CONCLUSION: There was no association between atopy status and either disease severity or recurrence in patients with chronic rhinosinusitis with nasal polyps, although atopic patients were younger than non-atopic patients. PMID- 27268095 TI - CYP1B1 mutational screening in a Portuguese cohort of primary congenital glaucoma patients. PMID- 27268096 TI - Compensatory load redistribution in Labrador retrievers when carrying different weights--a non-randomized prospective trial. AB - BACKGROUND: Retrievers are dogs particularly bred to retrieve birds or other small game, for the retrieval, the dogs are typically sent to the place where the shot game has fallen or to search the field for the wounded but still live game in order to return them to the hunter as quickly as possible. Examples of game animals are pheasants, mallard ducks and rabbits. For training, dummies with a variety of weights are used to simulate the retrieval of various types of game. The aim of this non-randomized prospective study was to investigate if peak vertical force, vertical impulse and paw pressure contact area are increased in the forelimbs when carrying different weights, and if the symmetrical weight distribution between contralateral limb pairs is disturbed. Ten actively working Labrador retrievers were walked over a pressure plate with or without carrying 0.5, 2.0 and 4.0 kg dummies. The aim of this study was to determine if vertical ground reaction forces and paw pressure contact area are increased in the forelimbs when carrying different weights, and if symmetrical weight distribution is disturbed between contralateral limb pairs. RESULTS: Peak vertical force and vertical impulse were significantly increased in the forelimbs and decreased in the hindlimbs in all weight carrying conditions. CONCLUSIONS: These results demonstrate the significant effects of carrying weight in the mouth on the ground reaction forces, which likely produce additional stress on the forelimb joints. Carry of game or a dummy is likely to alter the forelimb load distribution. PMID- 27268097 TI - Vicarious resilience in sexual assault and domestic violence advocates. AB - OBJECTIVE: There is little research related to sexual assault and domestic violence advocates' experiences, with the bulk of the literature focused on stressors and systemic barriers that negatively impact efforts to assist survivors. However, advocates participating in these studies have also emphasized the positive impact they experience consequent to their work. This study explores the positive impact. METHOD: Vicarious resilience, personal trauma experiences, peer relational quality, and perceived organizational support in advocates (n = 222) are examined. Also, overlap among the conceptual components of vicarious resilience is explored. RESULTS: The first set of multiple regressions showed that personal trauma experiences and peer relational health predicted compassion satisfaction and vicarious posttraumatic growth, with organizational support predicting only compassion satisfaction. The second set of multiple regressions showed that (a) there was significant shared variance between vicarious posttraumatic growth and compassion satisfaction; (b) after accounting for vicarious posttraumatic growth, organizational support accounted for significant variance in compassion satisfaction; and (c) after accounting for compassion satisfaction, peer relational health accounted for significant variance in vicarious posttraumatic growth. CONCLUSIONS: Results suggest that it may be more meaningful to conceptualize advocates' personal growth related to their work through the lens of a multidimensional construct such as vicarious resilience. Organizational strategies promoting vicarious resilience (e.g., shared organizational power, training components) are offered, and the value to trauma informed care of fostering advocates' vicarious resilience is discussed. (PsycINFO Database Record PMID- 27268098 TI - Examining the effects of alexithymia on the relation between posttraumatic stress disorder and over-reporting. AB - OBJECTIVE: Empirical examinations of the relation between posttraumatic stress disorder (PTSD) and objective measures of symptom over-reporting may be useful for identification of mechanisms of this previously observed relation. The present study examined the moderating effect of alexithymia, defined as a deficit in the ability to identify and describe emotions, on the relation between PTSD and over-reporting. METHOD: Seventy-five veterans diagnosed with PTSD were recruited from an outpatient Veterans Affairs facility and the community. Participants were administered the Miller Forensic Assessment of Symptoms Test, along with the Toronto Alexithymia Scale and PTSD Checklist within a larger study of behavioral and physiological correlates of PTSD. RESULTS: Hierarchical linear regression analyses showed a significant moderating effect of alexithymia, such that the relation between PTSD symptom severity and over-reporting was only significant in the presence of elevated alexithymia. Evaluation of the subscales of the Toronto Alexithymia Scale showed that the effect was greatest for the Difficulty Describing Emotions subscale. CONCLUSIONS: Alexithymia should be considered as a potential mechanism contributing to the over-reporting phenomena observed in the assessment and treatment of PTSD, and warrants further study. Brief interventions to improve understanding and description of emotional experiences may help to improve accuracy of symptom report. (PsycINFO Database Record PMID- 27268099 TI - New insights into the chemistry of Coenzyme Q-0: A voltammetric and spectroscopic study. AB - Coenzyme Q-0 (CoQ-0) is the only Coenzyme Q lacking an isoprenoid group on the quinoid ring, a feature important for its physico-chemical properties. Here, the redox behavior of CoQ-0 in buffered and non-buffered aqueous media was examined. In buffered aqueous media CoQ-0 redox chemistry can be described by a 2-electron 2-proton redox scheme, characteristic for all benzoquinones. In non-buffered media the number of electrons involved in the electrode reaction of CoQ-0 is still 2; however, the number of protons involved varies between 0 and 2. This results in two additional voltammetric signals, attributed to 2-electrons-1H(+) and 2-electrons-0H(+) redox processes, in which mono- and di-anionic compounds of CoQ-0 are formed. In addition, CoQ-0 exhibits a complex chemistry in strong alkaline environment. The reaction of CoQ-0 and OH(-) anions generates several hydroxyl derivatives as products. Their structures were identified with HPLC/MS. The prevailing radical reaction mechanism was analyzed by electron paramagnetic resonance spectroscopy. The hydroxyl derivatives of CoQ-0 have a strong antioxidative potential and form stable complexes with Ca(2+) ions. In summary, our results allow mechanistic insights into the redox properties of CoQ-0 and its hydroxylated derivatives and provide hints on possible applications. PMID- 27268100 TI - Postmating Reproductive isolation between strains of Drosophila willistoni. AB - Speciation can occur through the presence of reproductive isolation barriers that impede mating, restrict cross-fertilization, or render inviable/sterile hybrid progeny. The D. willistoni subgroup is ideally suited for studies of speciation, with examples of both allopatry and sympatry, a range of isolation barriers, and the availability of one species complete genome sequence to facilitate genetic studies of divergence. D. w. willistoni has the largest geographic distribution among members of the Drosophila willistoni subgroup, spanning from Argentina to the southern United States, including the Caribbean islands. A subspecies of D. w. willistoni, D. w. quechua, is geographically separated by the Andes mountain range and has evolved unidirectional sterility, in that only male offspring of D. w. quechua females * D. w. willistoni males are sterile. Whether D. w. willistoni flies residing east of the Andes belong to one or more D. willistoni subspecies remains unresolved. Here we perform fecundity assays and show that F1 hybrid males produced from crosses between different strains found in Central America, North America, and northern Caribbean islands are reproductively isolated from South American and southern Caribbean island strains as a result of unidirectional hybrid male sterility. Our results show the existence of a reproductive isolation barrier between the northern and southern strains and suggest a subdivision of the previously identified D. willistoni willistoni species into 2 new subspecies. PMID- 27268101 TI - Cortical morphometry in attention deficit/hyperactivity disorder: Contribution of thickness and surface area to volume. AB - Although lower brain volume is a consistent neuroimaging finding in attention deficit hyperactivity disorder (ADHD), we lack an understanding of whether this effect is driven by changes in cortical thickness or surface area, which are governed by distinct neurodevelopmental processes. This study examined ADHD control differences in cortical thickness, surface area and volume, and tests whether thickness and surface area mediates any observed volume differences. Magnetic resonance imaging (MRI) data was collected from 35 males with ADHD combined type and 35 typically developing control participants aged 9-17 years. Morphometric measures were examined for between group differences and the specific contribution of surface area and thickness to group differences in volume tested using mediation analysis. Individuals with ADHD had smaller total cortical volume (7.3%), surface area (4.3%), and mean cortical thickness (2.8%) compared to controls. Differences were pronounced in frontal and parietal lobes. Variance in volume as a function of ADHD diagnosis was accounted for at least in part by the relationship between diagnosis and each of cortical thickness and surface area, with regional variation in the relative contributions of these measures. The surface area of the precuneus was a major driver of volume differences, attesting to the potential relevance of this region for neurodevelopment in ADHD. Both surface area and cortical thickness play a significant mediating role in determining diagnostic differences in volume, with regional variation in the contribution of thickness and surface area to those volume differences, highlighting the importance of examining both cortical thickness and surface area in examining ADHD. PMID- 27268102 TI - Differential diagnosis and treatment of acute cauda equina syndrome in the human immunodeficiency virus positive patient: a case report and review of the literature. AB - BACKGROUND: Acute cauda equina syndrome is an uncommon but significant neurologic presentation due to a variety of underlying diseases. Anatomical compression of nerve roots, usually by a lumbar disk hernia is a common cause in the general population, while inflammatory, neoplastic, and ischemic causes have also been recognized. Among human immunodeficiency virus (HIV) infected patients with acquired immunodeficiency syndrome, infectious causes are encountered more frequently, the most prevalent of which are: cytomegalovirus, herpes simplex virus 1/2, varicella zoster virus, and Mycobacterium tuberculosis infections. Studies of cauda equina syndrome in well-controlled HIV infection are lacking. We describe such a case of cauda equina syndrome in a well-controlled HIV-infected patient, along with a brief review of the literature regarding the syndrome's diagnosis and treatment in individuals with HIV infection. CASE PRESENTATION: A 36-year-old Greek male, HIV-positive patient presented with perineal and left hemiscrotal numbness, lumbar pain, left-sided sciatica, and urinary incontinence. Magnetic resonance imaging of the patient's lumbar spine revealed intrathecal migration of a fragment from an intervertebral lumbar disk exerting pressure on the cauda equina. A cerebrospinal fluid examination, brain computed tomography scan, spine magnetic resonance imaging, and serological test results were negative for central nervous system infections. Our patient underwent emergency neurosurgical spinal decompression, which resolved most symptoms, except for mild urinary incontinence. CONCLUSIONS: Noninfectious etiologies may also cause cauda equina syndrome in HIV-infected individuals, especially in well-controlled disease under antiretroviral therapy. Prompt recognition and treatment of the underlying cause is important to minimize residual symptoms. Targeted antimicrobial chemotherapy is used to treat infectious causes, while prompt surgical decompression is favored for anatomical causes of cauda equina syndrome in the HIV-infected patient. PMID- 27268105 TI - Developmental Origins of Health and Disease - from a small body size at birth to epigenetics. AB - The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that several non-communicable diseases have their origins in prenatal life and in early childhood. This is believed to work through programming, an insult, taking place at a sensitive period of development, may have lifelong consequences, increasing and programming disease risk later in life. The Helsinki Birth Cohort Study (HBCS) has been focusing upon the importance of factors active during periods in early life and their influence on later health in 20,431 people born 1924-44. This review will focus upon findings from the HBCS over the past 20 years. Early growth patterns associated with coronary heart disease, type 2 diabetes and other health outcomes are described. The long-term health impact of maternal adiposity is also discussed. Potential underlying mechanisms explaining the associations are discussed including epigenetic factors. Key messages Several non-communicable diseases - including coronary heart disease and type 2 diabetes have their origins in early life. Early life programming during sensitive periods of development may permanently program future health and disease risk. Optimizing the health and lifestyle of women of reproductive age will have positive health consequences for their offspring. PMID- 27268106 TI - The influence of thermal trauma on pro- and anticoagulant activity of erythrocyte derived microvesicles. AB - The goal of this research was to study the influence of erythrocyte-derived microvesicles on hemostasis parameters during burn. It was found that the number of microvesicles derived from washed erythrocytes of burn patients after 1 day of storage at 37 degrees C was 4.2 times bigger than the number of microvesicles derived from erythrocytes of healthy donors. Hemocoagulation properties of erythrocyte-derived microvesicles of burn patients also change: according to the results of thromboelastography their procoagulant activity increases significantly, at the same time their antithrombin and fibrinilytic activity decrease. Thus, we can conclude that hepercoagulation during burn is to a certain extent caused by the disruption of the balance between procoagulant activity of erythrocyte-derived microvesicles and their antithrombin and fibrinolytic activity. Hypercoagulation effect of erythrocyte-derived microvesicles increases during burn not just because of their changed properties but also due to their increased number after thermal trauma. PMID- 27268104 TI - Which Combinations of Techniques and Modes of Delivery in Internet-Based Interventions Effectively Change Health Behavior? A Meta-Analysis. AB - BACKGROUND: Many online interventions designed to promote health behaviors combine multiple behavior change techniques (BCTs), adopt different modes of delivery (MoD) (eg, text messages), and range in how usable they are. Research is therefore needed to examine the impact of these features on the effectiveness of online interventions. OBJECTIVE: This study applies Classification and Regression Trees (CART) analysis to meta-analytic data, in order to identify synergistic effects of BCTs, MoDs, and usability factors. METHODS: We analyzed data from Webb et al. This review included effect sizes from 52 online interventions targeting a variety of health behaviors and coded the use of 40 BCTs and 11 MoDs. Our research also developed a taxonomy for coding the usability of interventions. Meta-CART analyses were performed using the BCTs and MoDs as predictors and using treatment success (ie, effect size) as the outcome. RESULTS: Factors related to usability of the interventions influenced their efficacy. Specifically, subgroup analyses indicated that more efficient interventions (interventions that take little time to understand and use) are more likely to be effective than less efficient interventions. Meta-CART identified one synergistic effect: Interventions that included barrier identification/ problem solving and provided rewards for behavior change reported an average effect size that was smaller (g=0.23, 95% CI 0.08-0.44) than interventions that used other combinations of techniques (g=0.43, 95% CI 0.27-0.59). No synergistic effects were found for MoDs or for MoDs combined with BCTs. CONCLUSIONS: Interventions that take little time to understand and use were more effective than those that require more time. Few specific combinations of BCTs that contribute to the effectiveness of online interventions were found. Furthermore, no synergistic effects between BCTs and MoDs were found, even though MoDs had strong effects when analyzed univariately in the original study. PMID- 27268103 TI - Interventions for improving adherence to treatment for latent tuberculosis infection: a systematic review. AB - BACKGROUND: Latent tuberculosis infection (LTBI) control relies on high initiation and completion rates of preventive treatment to preclude progression to tuberculosis disease. Specific interventions may improve initiation and completion rates. The objective was to systematically review data on determinants of initiation, adherence and completion of LTBI treatment, and on interventions to improve initiation and completion. METHODS: A systematic review of the literature (PubMed, Embase) published up to February 2014 was performed. Relevant prospective intervention studies were assessed using GRADE. RESULTS: Sixty-two articles reporting on determinants of treatment initiation and completion were included and 23 articles on interventions. Determinants of LTBI treatment completion include shorter treatment regimen and directly observed treatment (DOT, positive association), adverse events and alcohol use (negative association), and specific populations with LTBI (both positive and negative associations). A positive effect on completion was noted in intervention studies that used short regimens and social interventions; mixed results were found for intervention studies that used DOT or incentives. CONCLUSION: LTBI treatment completion can be improved by using shorter regimens and social interventions. Specific needs of the different populations with LTBI should be addressed taking into consideration the setting and condition in which the LTBI treatment programme is implemented. PMID- 27268107 TI - Direct detection of blood nitric oxide reveals a burn-dependent decrease of nitric oxide in response to Pseudomonas aeruginosa infection. AB - PURPOSE: Burn is associated with severe immune dysfunction, including an anti inflammatory state that occurs late after burn. While increased nitric oxide (NO) production is associated with severe infection and sepsis, the effect of burn trauma on these levels during a non-lethal infection remains unknown. We hypothesized that in a mouse model, (1) NO levels would be increased after infection without trauma and (2) burn would lead to decreased NO production even during infection. METHODS: Mice were infected via intra-tracheal inoculation with Pseudomonas aeruginosa 14 d following a 20% total body surface area contact burn. At 48h following infection, blood was drawn to quantify NO concentrations using a microfluidic electrochemical sensor. SIGNIFICANT FINDINGS: In uninjured mice, infection caused a significant increase in blood NO levels. Increases in NO occurred in a dose-dependent response to the bacterial inoculum. Following burn, an identical infection did not elicit increases in NO. CONCLUSIONS: While increases in NO are expected over the course of an infection without prior trauma, burn and subsequent immune suppression decreases NO levels even in the presence of infection. PMID- 27268108 TI - Burns management in ICU: Quality of the evidence: A systematic review. AB - BACKGROUND: The objective of this study was to assess the quality of readily available evidence regarding critical care aspects of the management of patients with severe burn injuries. METHOD: PUBMED, EMBASE, Cochrane Databases and bibliographies of included studies and burns review articles were searched from inception of databases to end of February 2015. We included systematic reviews, randomised controlled trials (RCTs) and cohort studies with concurrent controls on the topics of (a) fluid resuscitation (b) analgesia (c) haemodynamic monitoring and targets (d) ventilation (e) blood transfusion. The quality of the studies was assessed using validated tools. RESULTS: Fifty six studies fulfilled the inclusion criteria. Twenty three on fluid resuscitation, 22 on analgesia, nine on haemodynamic monitoring and two on ventilation. No studies were found on blood transfusion practice. There were ten systematic reviews, 38 RCTs and eight cohort studies with concurrent controls. The majority of studies were single centre trials with small numbers of patients, surrogate outcomes and high risk of bias. CONCLUSIONS: There is very little high quality evidence to guide clinical practice in early management of the severely burnt patient. Eleven of 56 studies found in our search of critical care topics were of good methodological quality with low risk of bias. PMID- 27268109 TI - Differing patterns in thermal injury incidence and hospitalisations among 0-4 year old children from England. AB - OBJECTIVE: To describe patterns in thermal injury incidence and hospitalisations by age, gender, calendar year and socioeconomic status among 0-4 year olds in England for the period 1998-2013. PARTICIPANTS: 708,050 children with linked primary care and hospitalisation data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES), respectively. ANALYSIS: Incidence rates of all thermal injuries (identified in CPRD and/or HES), hospitalised thermal injuries, and serious thermal injuries (hospitalised for >=72h). Adjusted incidence rate ratios (IRR) and 95% confidence intervals (95%CI), estimated using Poisson regression. RESULTS: Incidence rates of all thermal injuries, hospitalised thermal injuries, and serious thermal injuries were 59.5 per 10,000 person-years (95%CI 58.4-60.6), 11.3 (10.8-11.8) and 2.15 (1.95-2.37), respectively. Socioeconomic gradients, between the most and least deprived quintiles, were steepest for serious thermal injuries (IRR 3.17, 95%CI 2.53-3.96). Incidence of all thermal injuries (IRR 0.64, 95%CI 0.58-0.70) and serious thermal injuries (IRR 0.44, 95%CI 0.33-0.59) reduced between 1998/9 and 2012/13. Incidence rates of hospitalised thermal injuries did not significantly change over time. CONCLUSION: Incidence of all thermal injuries and those hospitalised for >=72h reduced over time. Steep socioeconomic gradients support continued targeting of preventative interventions to those living in the most deprived areas. PMID- 27268110 TI - A prospective clinical trial comparing Biobrane1 Dressilk1 and PolyMem1 dressings on partial-thickness skin graft donor sites. PMID- 27268111 TI - The Effectiveness of Platelet-Rich Plasma in the Treatment of Tendinopathy: A Meta-analysis of Randomized Controlled Clinical Trials. AB - BACKGROUND: Tendinopathy is very common in the general population. There are increasing numbers of clinical studies referring to platelet-rich plasma (PRP) and platelet-poor plasma (PPP) as treatments for tendinopathy. PURPOSE: To perform a meta-analysis of the outcomes of the PRP groups by preparation method and injection technique in tendinopathy. To determine the clinical effectiveness of the preparations and to evaluate the effect of controls used in the studies reviewed. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The PubMed, EMBASE, CINAHL, and Medline databases were searched in March 2012, April 2014, and August 2015, and randomized controlled trials using autologous blood, PRP, PPP, or autologous conditioned plasma in tendinopathy with outcome measures of pain and follow-up time of 3 months were included in this review. Trials including surgery, tendon tears, and muscle or ligament injuries were excluded. Study quality was assessed using the Cochrane Collaboration risk-of-bias tool by 2 reviewers. Data were pooled using random-effects meta-analysis. The primary outcome measure was a change in pain intensity. Where more than 1 pain scale was included, a functional score was selected ahead of a visual analog scale score. RESULTS: A total of 18 studies (1066 participants) were included. Eight studies were deemed to be at low risk of bias. The most significant outcomes in the PRP groups were seen in those treated with highly cellular leukocyte-rich PRP (LR PRP) preparations: GPS kit (standardized mean difference [SMD], 35.75; 95% CI, 28.40-43.10), MyCells kit (SMD, 31.84; 95% CI, 17.56-46.13), Prosys kit (SMD, 42.99; 95% CI, 37.73-48.25), and unspecified LR-PRP (SMD, 34.62; 95% CI, 31.69 37.55). When the LR-PRP system types were grouped, there was a strongly positive effect (SMD, 36.38; 95% CI, 34.00-38.77) when compared with leukocyte-poor PRP (SMD, 26.77; 95% CI, 18.31-35.22). In assessing the control groups, there was no clear difference between different types of control injections: saline (SMD, 14.62; 95% CI, 10.74-18.50), local anesthetic (SMD, 15.00; 95% CI, 7.66-22.34), corticosteroid (SMD, 23.82; 95% CI, 10.74-18.50), or dry needling (SMD, 25.22; 95% CI, 21.27-29.16). CONCLUSION: There is good evidence to support the use of a single injection of LR-PRP under ultrasound guidance in tendinopathy. Both the preparation and intratendinous injection technique of PRP appear to be of great clinical significance. PMID- 27268112 TI - Does wine glass size influence sales for on-site consumption? A multiple treatment reversal design. AB - BACKGROUND: Wine glass size can influence both perceptions of portion size and the amount poured, but its impact upon purchasing and consumption is unknown. This study aimed to examine the impact of wine glass size on wine sales for on site consumption, keeping portion size constant. METHODS: In one establishment (with separate bar and restaurant areas) in Cambridge, England, wine glass size (Standard; Larger; Smaller) was changed over eight fortnightly periods. The bar and restaurant differ in wine sales by the glass vs. by the bottle (93 % vs. 63 % by the glass respectively). RESULTS: Daily wine volume purchased was 9.4 % (95 % CI: 1.9, 17.5) higher when sold in larger compared to standard-sized glasses. This effect seemed principally driven by sales in the bar area (bar: 14.4 % [3.3, 26.7]; restaurant: 8.2 % [-2.5, 20.1]). Findings were inconclusive as to whether sales were different with smaller vs. standard-sized glasses. CONCLUSIONS: The size of glasses in which wine is sold, keeping the portion size constant, can affect consumption, with larger glasses increasing consumption. The hypothesised mechanisms for these differential effects need to be tested in a replication study. If replicated, policy implications could include considering glass size amongst alcohol licensing requirements. TRIAL REGISTRATION: ISRCTN registry: ISRCTN12018175 . Registered 12(th) May 2015. PMID- 27268113 TI - Effect of plant growth-promoting bacteria on the growth and fructan production of Agave americana L. AB - The effect of plant growth-promoting bacteria inoculation on plant growth and the sugar content in Agave americana was assessed. The bacterial strains ACO-34A, ACO 40, and ACO-140, isolated from the A. americana rhizosphere, were selected for this study to evaluate their phenotypic and genotypic characteristics. The three bacterial strains were evaluated via plant inoculation assays, and Azospirillum brasilense Cd served as a control strain. Phylogenetic analysis based on the 16S rRNA gene showed that strains ACO-34A, ACO-40 and ACO-140 were Rhizobium daejeonense, Acinetobacter calcoaceticus and Pseudomonas mosselii, respectively. All of the strains were able to synthesize indole-3-acetic acid (IAA), solubilize phosphate, and had nitrogenase activity. Inoculation using the plant growth promoting bacteria strains had a significant effect (p<0.05) on plant growth and the sugar content of A. americana, showing that these native plant growth promoting bacteria are a practical, simple, and efficient alternative to promote the growth of agave plants with proper biological characteristics for agroindustrial and biotechnological use and to increase the sugar content in this agave species. PMID- 27268114 TI - Process optimization for production and purification of a thermostable, organic solvent tolerant lipase from Acinetobacter sp. AU07. AB - The purpose of this study was to isolate, purify and optimize the production conditions of an organic solvent tolerant and thermostable lipase from Acinetobacter sp. AU07 isolated from distillery waste. The lipase production was optimized by response surface methodology, and a maximum production of 14.5U/mL was observed at 30 degrees C and pH 7, using a 0.5% (v/v) inoculum, 2% (v/v) castor oil (inducer), and agitation 150rpm. The optimized conditions from the shake flask experiments were validated in a 3L lab scale bioreactor, and the lipase production increased to 48U/mL. The enzyme was purified by ammonium sulfate precipitation and ion exchange chromatography and the overall yield was 36%. SDS-PAGE indicated a molecular weight of 45kDa for the purified protein, and Matrix assisted laser desorption/ionization time of flight analysis of the purified lipase showed sequence similarity with GDSL family of lipases. The optimum temperature and pH for activity of the enzyme was found to be 50 degrees C and 8.0, respectively. The lipase was completely inhibited by phenylmethylsulfonyl fluoride but minimal inhibition was observed when incubated with ethylenediaminetetraacetic acid and dithiothreitol. The enzyme was stable in the presence of non-polar hydrophobic solvents. Detergents like SDS inhibited enzyme activity; however, there was minimal loss of enzyme activity when incubated with hydrogen peroxide, Tween 80 and Triton X-100. The kinetic constants (Km and Vmax) revealed that the hydrolytic activity of the lipase was specific to moderate chain fatty acid esters. The Vmax, Km and Vmax/Km ratio of the enzyme were 16.98U/mg, 0.51mM, and 33.29, respectively when 4-nitrophenyl palmitate was used as a substrate. PMID- 27268116 TI - Performance of two alternative methods for Listeria detection throughout Serro Minas cheese ripening. AB - The ability of pathogens to survive cheese ripening is a food-security concern. Therefore, this study aimed to evaluate the performance of two alternative methods of analysis of Listeria during the ripening of artisanal Minas cheese. These methods were tested and compared with the conventional method: Lateral Flow SystemTM, in cheeses produced on laboratory scale using raw milk collected from different farms and inoculated with Listeria innocua; and VIDAS((r))-LMO, in cheese samples collected from different manufacturers in Serro, Minas Gerais, Brazil. These samples were also characterized in terms of lactic acid bacteria, coliforms and physical-chemical analysis. In the inoculated samples, L. innocua was detected by Lateral Flow SystemTM method with 33% false-negative and 68% accuracy results. L. innocua was only detected in the inoculated samples by the conventional method at 60-days of cheese ripening. L. monocytogenes was not detected by the conventional and the VIDAS((r))-LMO methods in cheese samples collected from different manufacturers, which impairs evaluating the performance of this alternative method. We concluded that the conventional method provided a better recovery of L. innocua throughout cheese ripening, being able to detect L. innocua at 60-day, aging period which is required by the current legislation. PMID- 27268115 TI - The prevalence of aminoglycoside-modifying enzyme and virulence genes among enterococci with high-level aminoglycoside resistance in Inner Mongolia, China. AB - This study highlights the prevalence of aminoglycoside-modifying enzyme genes and virulence determinants among clinical enterococci with high-level aminoglycoside resistance in Inner Mongolia, China. Screening for high-level aminoglycoside resistance against 117 enterococcal clinical isolates was performed using the agar-screening method. Out of the 117 enterococcal isolates, 46 were selected for further detection and determination of the distribution of aminoglycoside modifying enzyme-encoding genes and virulence determinants using polymerase chain reaction -based methods. Enterococcus faecium and Enterococcus faecalis were identified as the species of greatest clinical importance. The aac(6')-Ie-aph(2") Ia and ant(6')-Ia genes were found to be the most common aminoglycoside-modifying enzyme genes among high-level gentamicin resistance and high-level streptomycin resistance isolates, respectively. Moreover, gelE was the most common virulence gene among high-level aminoglycoside resistance isolates. Compared to Enterococcus faecium, Enterococcus faecalis harbored multiple virulence determinants. The results further indicated no correlation between aminoglycoside modifying enzyme gene profiles and the distribution of virulence genes among the enterococcal isolates with high-level gentamicin resistance or high-level streptomycin resistance evaluated in our study. PMID- 27268117 TI - CTX-M extended-spectrum beta-lactamase-producing Klebsiella spp, Salmonella spp, Shigella spp and Escherichia coli isolates in Iranian hospitals. AB - This study was conducted in Iran in order to assess the distribution of CTX-M type ESBLs producing Enterobacteriaceae. From January 2012 to December 2013, totally 198 E. coli, 139 Klebsiella spp, 54 Salmonella spp and 52 Shigella spp from seven hospitals of six provinces in Iran were screened for resistance to extended-spectrum cephalosporins. After identification and susceptibility testing, isolates presenting multiple-drug resistance (MDR) were evaluated for ESBL production by the disk combination method and by Etest using (cefotaxime and cefotaxime plus clavulanic acid). All isolates were also screened for blaCTX-M using conventional PCR. A total of 42.92%, 33.81%, 14.81% and 7.69% of the E. coli, Klebsiella spp, Salmonella spp and Shigella spp isolates were MDR, respectively. The presence of CTX-M enzyme among ESBL-producing isolates was 85.18%, 77.7%, 50%, and 66.7%, in E. coli, Klebsiella spp, Salmonella spp and Shigella spp respectively. The overall presence of CTX-M genes in Enterobacteriaceae was 15.4% and among the resistant isolates was 47.6%. This study indicated that resistance to beta-lactams mediated by CTX-M enzymes in Iran had similar pattern as in other parts of the world. In order to control the spread of resistance, comprehensive studies and programs are needed. PMID- 27268118 TI - Galectin-related protein: An integral member of the network of chicken galectins 1. From strong sequence conservation of the gene confined to vertebrates to biochemical characteristics of the chicken protein and its crystal structure. PMID- 27268119 TI - The concurrent and predictive validity of the Dutch version of the Communicative Development Inventory in children with Down Syndrome for the assessment of expressive vocabulary in verbal and signed modalities. AB - The expressive vocabulary of children with Down Syndrome (DS) is generally measured with parental reports, such as the Communicative Development Inventory (CDI), given that standardized tests for assessing vocabulary levels may be too difficult for most young children with DS. The CDI provides important insight into the parents' perception of their child's vocabulary development. The CDI has proven to be a valid measurement of expressive vocabulary, spoken and gestural, in typical and atypical populations. The validity in children with DS is not well established and signed vocabulary is often not included. This longitudinal study examined the concurrent and predictive validity of the Dutch version of the CDI (N-CDI) in children with DS between 2;0 and 7;6 years old to assess spoken and signed vocabulary. N-CDI scores were assessed on strength of association with mental age, an expressive vocabulary test and spontaneous language analyses in a play setting with parents at T1 and T2 (1.5 years later), and a therapy setting with speech language pathologists at T1. The results of the present study show that the N-CDI is a valuable and valid measurement of expressive vocabulary in children with DS. Strengths and weaknesses of several assessment methods for expressive vocabulary are discussed. PMID- 27268120 TI - Mapping Sources of Food Safety Information for U.S. Consumers: Findings From a National Survey. AB - This research examines the sources from which U.S. consumers obtain their food safety information. It seeks to determine differences in the types of information sources used by U.S. consumers of different sociodemographic background, as well as the relationships between the types of information sources used and food safety risk perceptions. Analyzing the 2010 Food Safety Survey (N = 4,568) conducted by the U.S. Food and Drug Administration, we found that age, gender, education, and race predicted the use of different sources for food safety information. Additionally, use of several information sources predicted perceived susceptibility to foodborne illnesses and severity of food contamination. Implications of the findings for food safety risk communication are discussed. PMID- 27268122 TI - [Clinical trials, science and economy]. PMID- 27268123 TI - Coumarin-Spiropyran Dyad with a Hydrogenated Pyran Moiety for Rapid, Selective, and Sensitive Fluorometric Detection of Cyanide Anion. AB - We synthesized a coumarin-spiropyran dyad with a hydrogenated pyran moiety (2), behaving as an off-on type fluorescent receptor for rapid, selective, and sensitive detection of cyanide anion (CN(-)) in aqueous media. The receptor itself shows almost no fluorescence with a quantum yield < 0.01, due to the delocalization of pi-electrons over the molecule. Selective nucleophilic addition of CN(-) to the spirocarbon of the molecule rapidly promotes spirocycle opening within only 3 min. This leads to localization of pi-electrons on the coumarin moiety and exhibits strong light-blue fluorescence at 459 nm with very high quantum yield (0.52). As a result of this, the receptor facilitates rapid, selective, and sensitive fluorometric detection of CN(-) as low as 1.0 MUM. PMID- 27268124 TI - Clinical Validation of a CXCR4 Mutation Screening Assay for Waldenstrom Macroglobulinemia. AB - OBJECTIVES: Waldenstrom macroglobulinemia (WM) is a B-cell lymphoma characterized by the accumulation of lymphocytes and plasmacytic cells in the bone marrow and by excess production of immunoglobulin M in serum. WM has been closely linked with the MYD88(L265P) mutation. Whole genome sequencing has identified somatic mutations in the CXCR4 gene in ~29% of WM cases with MYD88(L265P). CXCR4 mutations may interfere with treatment response to ibrutinib. The goal of this study was to design and validate a clinical assay to detect CXCR4 mutations. METHODS: Thirty-three low-grade B-cell lymphomas with plasmacytic differentiation (23 MYD88(L265P) and 10 MYD88(WT)) involving various samples types (fresh and formalin-fixed tissues) formed the study group. We designed and validated Sanger sequencing and pyrosequencing assays to detect mutations in CXCR4 in a Clinical Laboratory Improvement Amendments-approved clinical laboratory. RESULTS: We identified 8 cases with CXCR4 mutations, including 5 single nucleotide substitutions (3 resulting in p.S338* and 1 in p.R334*), and 3 insertion/deletions. Seven of 8 CXCR4 mutated cases were also MYD88(L265P) mutant. Among the single nucleotide substitutions, we identified a novel missense variant (p.L326P) and a previously reported variant (G335S) of uncertain clinical significance. CONCLUSIONS: We successfully validated a set of clinical assays to detect mutations in CXCR4 mutations in a clinical laboratory. PMID- 27268125 TI - New Mechanistic Insights on the Selectivity of Transition-Metal-Catalyzed Organic Reactions: The Role of Computational Chemistry. AB - With new advances in theoretical methods and increased computational power, applications of computational chemistry are becoming practical and routine in many fields of chemistry. In organic chemistry, computational chemistry plays an indispensable role in elucidating reaction mechanisms and the origins of various selectivities, such as chemo-, regio-, and stereoselectivities. Consequently, mechanistic understanding improves synthesis and assists in the rational design of new catalysts. In this Account, we present some of our recent works to illustrate how computational chemistry provides new mechanistic insights for improvement of the selectivities of several organic reactions. These examples include not only explanations for the existing experimental observations, but also predictions which were subsequently verified experimentally. This Account consists of three sections discuss three different kinds of selectivities. The first section discusses the regio- and stereoselectivities of hydrosilylations of alkynes, mainly catalyzed by [Cp*Ru(MeCN)3](+) or [CpRu(MeCN)3](+). Calculations suggest a new mechanism that involves a key ruthenacyclopropene intermediate. This mechanism not only explains the unusual Markovnikov regio-selectivity and anti-addition stereoselectivity observed by Trost and co-workers, but also motivated further experimental investigations. New intriguing experimental observations and further theoretical studies led to an extension of the reaction mechanism. The second section includes three cases of meta-selective C-H activation of aryl compounds. In the case of Cu-catalyzed selective meta-C-H activation of aniline, a new mechanism that involves a Cu(III)-Ar-mediated Heck like transition state, in which the Ar group acts as an electrophile, was proposed. This mechanism predicted a higher reactivity for more electron deficient Ar groups, which was supported by experiments. For two template mediated, meta-selective C-H bond activations catalyzed by Pd(II), different mechanisms were derived for the two templates. One involves a dimeric Pd-Pd or Pd Ag active catalyst, and the other involves a monomeric Pd catalyst, in which a monoprotected amino acid coordinates in a bidentate fashion and serves as an internal base for C-H activation. The third section discusses a desymmetry strategy in asymmetric synthesis. The construction of rigid skeletons is critical for these catalysts to distinguish two prochiral groups. Overall, fruitful collaborations between computational and experimental chemists have provided new and comprehensive mechanistic understanding and insights into these useful reactions. PMID- 27268121 TI - Biological markers of prognosis, response to therapy and outcome in ovarian carcinoma. AB - INTRODUCTION: Ovarian cancer (OvCa) is among the most common types of cancer and is the leading cause of death from gynecological malignancies in western countries. Cancer biomarkers have a potential for improving the management of OvCa patients at every point from screening and detection, diagnosis, prognosis, follow up, response to therapy and outcome. AREAS COVERED: The literature search has indicated a number of candidate biomarkers have recently emerged that could facilitate the molecular definition of OvCa, providing information about prognosis and predicting response to therapy. These potentially promising biomarkers include immune cells and their products, tumor-derived exosomes, nucleic acids and epigenetic biomarkers. Expert commentary: Although most of the biomarkers available today require prospective validation, the development of noninvasive liquid biopsy-based monitoring promises to improve their utility for evaluations of prognosis, response to therapy and outcome in OvCa. PMID- 27268126 TI - Doubly N-Methylated Porphyrinoids. AB - Chirality-induced aromatic pi-electronic macrocycles, porphyrin and corroles, were synthesized through doubly inner N-methylation through multistep and one-pot reactions, respectively. The exact structures of doubly N-methylated porphyrin and corroles were revealed by single-crystal synchrotron X-ray analysis, exhibiting two N-methyl groups located on neighboring pyrrole rings in up/down conformations. These doubly inner N-substitutions of the pi-electronic macrocycles induced distorted geometries, resulting in chiroptical properties after optical resolutions. PMID- 27268127 TI - Which Is Better? "Live" Surgical Broadcasts vs "As-Live" Surgical Broadcasts. AB - INTRODUCTION: Recently, the role of "live" surgical broadcasts (LSB) as an educational tool to demonstrate surgical techniques at conferences has been challenged, with concerns surrounding the well-being and safety of the patient as well as the surgeon. There have been notions that "as-live" surgical broadcasts (ALSB), prerecorded unedited videos showing either the whole procedure or key features, may be educationally superior. Our study was hence conducted to determine which was deemed better by a diverse group of international urologists. METHODS: All participants of the World Congress of Endourology held in October 2015 in London were invited to complete an electronic survey using the conference app regarding LSB demonstrations compared with ASLB, before the congress and again after the congress. Only ALSB videos were used in the congress. RESULTS: Both pre- and postconference surveys showed that 76.9% and 78.2% of the participants, respectively, perceived that more teaching could be achieved in less time using ASLB. 52.8% and 60.3% of respondents indicated ALSB as being superior to LSB before and after the conference, respectively. Furthermore, 52.8% and 54.5% of respondents regarded ALSB videos as having more educational value than LSB before and after the conference, respectively. CONCLUSION: There was little perceived difference between ALSB and LSB, showing that ALSB are at least noninferior as an educational tool. In view of the numerous ethical and logistical issues with LSB, we would advocate ASLB as the educational tool of choice for future surgical demonstration at conferences. PMID- 27268128 TI - Local Persistence of Novel MRSA Lineage after Hospital Ward Outbreak, Cambridge, UK, 2011-2013. PMID- 27268129 TI - Time to seroconversion of HBsAg to anti-HBs in individuals who lost HBsAg during follow-up. AB - To determine the time to appearance of antibody against hepatitis B surface antigen (anti-HBs) after clearance of hepatitis B surface antigen (HBsAg) in chronically infected individuals, we followed up 3963 cases with positive antibody against hepatitis B e antigen (anti-HBe) from 1991 to 2014. Of these, 101 (67 males, 34 females) lost HBsAg. These serocleared cases were checked every 6-month interval regarding HBsAg, anti-HBs, liver function tests, and liver sonography. Hepatitis B virus DNA was assessed at the time of seroclearance or the appearance of anti-HBs. The mean age of these patients at entry to this study was 34.4 +/- 13 years. The mean follow-up duration until seroclearance of HBsAg was 6.6 +/- 4.3 years. After the mean follow-up of 43.7 +/- 45 months, anti-HBs appeared in 64 (63.4%) cases. The cumulative probabilities of anti-HBs appearance for 2, 5 and 10 years were 24.3%, 58% and 78.2%, respectively. The appearance of anti-HBs was associated with age ?35 years and seroclearance of HBsAg (hazard ratio 1.96, 95% confidence interval 1.32-3.38, P = 0.016) but not with sex. The results show that anti-HBs may develop in 78.2% of cases within 10 years of HBsAg clearance. Age ?35 years at HBsAg loss was associated with earlier development of anti-HBs. PMID- 27268130 TI - Targeting Candida albicans filamentation for antifungal drug development. AB - Candida albicans remains the main etiological agent of candidiasis, as this otherwise normal commensal of humans is capable of causing active infection in immune- and medically-compromised patients. The high morbidity and mortality rates associated with candidiasis, coupled with the emergence of drug resistance demand the development of novel therapeutic strategies. However, there is a paucity of selective targets that can be exploited in the development of new antifungals. Contrary to conventional antibiotics that kill or curtail growth, specifically targeting virulence mechanisms represents an attractive option for antifungal drug development. In C. albicans, a growing body of research over the last few decades has provided important insights into its virulence factors and their contribution to the pathogenesis of candidiasis. Of these, filamentation is the one that has received the most attention and perhaps shows the most promise as a target for new anti-virulence strategies to combat C. albicans infections. PMID- 27268131 TI - Reporting behaviour change interventions: do the behaviour change technique taxonomy v1, and training in its use, improve the quality of intervention descriptions? AB - BACKGROUND: Behaviour change interventions are likely to be reproducible only if reported clearly. We assessed whether the behaviour change technique taxonomy version 1 (BCTTv1), with and without training in identifying BCTs, improves the clarity and replicability of written reports of observed behaviour change interventions. METHODS: Three studies assessed effects of using and training in the use of BCTTv1 on the clarity and replicability of intervention descriptions written after observing videos of smoking cessation interventions. Study 1 examined the effects of using and not using BCTTv1. Study 2 examined the effects of using BCTTv1 and training in use of BCTTv1 compared no use and no training. Study 3 employed a within-group design to assess change in descriptions written before and after training. One-hundred and 66 'writers' watched videos of behaviour change interventions and wrote descriptions of the active components delivered. In all studies, the participants' written descriptions were evaluated by (i) 12 'raters' (untrained in BCTTv1) for clarity and replicability and (ii) 12 'coders' (trained in BCTTv1) for reliability of BCT coding. Writers rated the usability and accessibility of using BCTTv1 to write descriptions. RESULTS: Ratings of clarity and replicability did not differ between groups in study 1 (all ps > 0.05), were poorer for trained users in study 2 (all ps < 0.01) and improved following training in study 3 (all ps < 0.05). BCT identification was more reliable from descriptions written by trained BCTTv1 users (p < 0.05; study 2) but not simple use of BCTTv1 (p = 0.93; study 1) or by writers who had written a description without BCTTv1, before training (p = 0.50; study 3). Writers reported that using BCTTv1 was difficult but 'useful', 'good' and 'desirable' and that their descriptions would be clear and replicable (all means above mid-point of the scale). CONCLUSIONS: Effects of training to use BCTTv1 on the quality of written reports of observed interventions were mixed, with some suggestion of improved clarity and replicability of reporting in the within- (study 3) but not the between-group studies (studies 1 and 2). Potential benefits of using BCTTv1 may have been limited by the artificial nature and time constraints of the task. PMID- 27268132 TI - Vicious circle between progressive right ventricular dilatation and pulmonary regurgitation in patients after tetralogy of Fallot repair? Right heart enlargement promotes flow reversal in the left pulmonary artery. AB - BACKGROUND: The left pulmonary artery (LPA) contributes more than the right (RPA) to total pulmonary regurgitation (PR) in patients after tetralogy of Fallot (TOF) repair, but the mechanism of this difference is not well understood. This study aimed to analyze the interplay between heart and lung size, mediastinal geometry, and differential PR. METHODS: Forty-eight Cardiovascular Magnetic Resonance (CMR) studies in patients after TOF repair were analyzed. In addition to the routine blood flow and ventricular volume quantification cardiac angle between the thoracic anterior-posterior line and the interventricular septum, right and left lung areas as well as right and left hemithorax areas were measured on an axial image. Statistical analysis was performed to compare flow parameters between RPA and LPA and to assess correlation among right ventricular volume, pulmonary blood flow parameters and lung area. RESULTS: There was no difference between LPA and RPA diameters. The LPA showed significantly less total forward flow (2.49 +/- 0.87 L/min/m(2) vs 2.86 +/- 0.89 L/min/m(2); p = 0.02), smaller net forward flow (1.40 +/- 0.51 vs 1.89 +/- 0.60 mL/min/m(2); p = <0.001), and greater regurgitant fraction (RF) (34 +/- 10 % vs 43 +/- 12 %; p = 0.001) than the RPA. There was no difference in regurgitant flow volume between RPA and LPA (p = 0.29). Indexed right ventricular end-diastolic volume (RVEDVi) correlated with LPA RF (R = 0.48, p < 0.001), but not with RPA RF (p = 0.09). Larger RVEDVi correlated with a more leftward cardiac axis (R = 0.46, p < 0.001) and with smaller left lung area (R = 0.58, p < 0.001). LPA RF, but not RPA RF, correlated inversely with left lung area (R = -0.34, p = 0.02). The follow-up CMRs in 20 patients showed a correlation of the rate of RV enlargement with the rates of LPA RF worsening (R = 0.50, p = 0.03), and of increasing left lung compression (R = -0.55, p = 0.012). CONCLUSION: An enlarged and levorotated heart is associated with left lung compression and impaired flow into the left lung. PMID- 27268134 TI - New virus discovered in blood supply: Human hepegivirus-1 (HHpgV-1). PMID- 27268135 TI - Generation of Hierarchically Ordered Structures on a Polymer Film by Electrohydrodynamic Structure Formation. AB - The extensive applications of hierarchical structures in optoelectronics, micro/nanofluidics, energy conservation, etc., have led to the development of a variety of approaches for their fabrication, which can be categorized as bottom up or top-down strategies. Current bottom-up and top-down strategies bear a complementary relationship to each other due to their processing characteristics, i.e., the advantages of one method correspond to the disadvantages of the other, and vice versa. Here we propose a novel method based on electrohydrodynamic structure formation, aimed at combining the main advantages of the two strategies. The method allows the fabrication of a hierarchically ordered structure with well-defined geometry and high mechanical durability on a polymer film, through a simple and low-cost process also suitable for mass-production. In this approach, upon application of an electric field between a template and a substrate sandwiching an air gap and a polymer film, the polymer is pulled toward the template and further flows into the template cavities, resulting in a hierarchical structure with primary and secondary patterns determined by electrohydrodynamic instability and by the template features, respectively. In this work, the fabrication of a hierarchical structure by electrohydrodynamic structure formation is studied using numerical simulations and experimental tests. The proposed method is then employed for the one-step fabrication of a hierarchical structure exhibiting a gradual transition in the periodicity of the primary structure using a slant template and a flat polymer film, which presents an excellent performance on controllable wettability. PMID- 27268133 TI - Patients' Use of Multiple Hospitals in a Major US City: Implications for Population Management. AB - Understanding how often patients seek care from multiple hospitals is important for care of individuals and populations, but it is not routinely measured because of lack of data. This study used data from a health information exchange (HIE) to measure the frequency with which patients seek care from multiple hospitals. This was a retrospective cohort study (2010-2011) of all patients who sought emergency department (ED) or inpatient care at 6 participating hospitals in Manhattan. The study found that all 6 hospitals shared patients with each of the other hospitals and that 10.0% of all ED visits and 9.1% of all admissions were for patients who had been seen in a different hospital in the past 12 months. Patients are frequently seen by multiple hospitals, which poses a challenge for clinical care and population management. By capturing which patients are seen where and when, HIEs are well suited for facilitating population management. PMID- 27268136 TI - Polyhydrides of Platinum Group Metals: Nonclassical Interactions and sigma-Bond Activation Reactions. AB - The preparation, structure, dynamic behavior in solution, and reactivity of polyhydride complexes of platinum group metals, described during the last three decades, are contextualized from both organometallic and coordination chemistry points of view. These compounds, which contain dihydrogen, elongated dihydrogen, compressed dihydride, and classical dihydride ligands promote the activation of B H, C-H, Si-H, N-H, O-H, C-C, C-N, and C-F, among other sigma-bonds. In this review, it is shown that, unlike other more mature areas, the chemistry of polyhydrides offers new exciting conceptual challenges and at the same time the possibility of interacting with other fields including the conversion and storage of regenerative energy, organic synthetic chemistry, drug design, and material science. This wide range of possible interactions foresees promising advances in the near future. PMID- 27268137 TI - The effect of tooth brushing, irrigation, and topical tetracycline administration on the reduction of oral bacteria in mechanically ventilated patients: a preliminary study. AB - BACKGROUND: One of the main causes of ventilator-associated pneumonia (VAP) is thought to be aspiration of oropharyngeal fluid containing pathogenic microorganisms. The aim of this study was to examine the effects of various oral care methods on the reduction of oral bacteria during intubation. METHODS: First, the effect of mechanical oral cleaning was investigated. The bacterial count on the tongue and in the oropharyngeal fluid was measured after tooth brushing, irrigation, and three hours after irrigation in mechanically ventilated patients at the intensive care unit (ICU). Next, the efficacy of topical administration of tetracycline and povidone iodine on the inhibition of bacterial growth on the tongue and in the oropharyngeal fluid was examined in oral cancer patients during neck dissection. RESULTS: The number of bacteria in the oropharyngeal fluid was approximately 10(5)-10(6) cfu/mL before surgery, but increased to 10(8) cfu/mL after intubation. Oral care with tooth brushing and mucosal cleaning did not reduce oral bacteria, while irrigation of the oral cavity and oropharynx significantly decreased it to a level of 10(5) cfu/mL (p < 0.001). However, oral bacteria increased again to almost 10(8) cfu/mL within three hours of irrigation. Oral bacteria did not decrease by topical povidone iodine application. In contrast, 30 min after topical administration of tetracycline, the number of oral bacteria decreased to 10(5) cfu/mL, and remained under 10(6) cfu/mL throughout the entire experimental period of 150 min. CONCLUSIONS: While the present studies are only preliminary, these results indicate that irrigation of the oral cavity and oropharynx followed by topical antibiotic administration may reduce oral bacteria in mechanically ventilated patients. TRIAL REGISTRATION: UMIN000018318 , 1 August 2015. PMID- 27268138 TI - Prevalence and correlates of depressive symptoms in adult patients with pulmonary tuberculosis in the Southwest Region of Cameroon. AB - BACKGROUND: Tuberculosis (TB) remains a global health challenge and depression is a significant contributor to the global burden of disease. Current evidence suggests that there is an association between depressive symptoms and TB, lower adherence to treatment, and increased morbidity and mortality. However, there is paucity of data regarding these associations in Cameroon. This study aimed to determine the prevalence and correlates of depression in adult patients with pulmonary TB (PTB) in the Southwest Region of Cameroon. METHODS: A hospital-based cross-sectional study involving 265 patients with PTB was conducted from 2(nd) January to 31(st) March 2015 in the Limbe Regional Hospital and the Kumba District Hospital. Depression was diagnosed using the standard nine-item Patient Health Questionnaire, and classified as none, mild or moderate. Logistic regressions were used to investigate correlates of depression in these patients. RESULTS: Of the 265 patients (mean age 36.9 +/- 10 years) studied, 136 (51.3 %) were female. The prevalence of depression was 61.1 % (95 % CI: 55.1-66.8), with a significant proportion (36.6 %) having mild depression. Multivariable logistic regression analysis showed that being female (aOR = 3.0, 95 % CI (1.7-5.5), P < 0.001), having a family history of mental illness (aOR = 2.5, 95 % CI: 1.3-5.4, P > 0.05), being on retreatment for TB (aOR = 11.2, 95 % CI: 5.2-31.1, P < 0.001), having discontinued treatment (aOR = 8.2, 95 % CI: 1.1-23.3, P < 0.05) and having a HIV/TB co-infection (aOR = 2.5, 95 % CI: 1.2-6.5, P < 0.001) were factors associated with having a higher chance of being depressed. CONCLUSION: Our study suggests that there is a high prevalence of depression among PTB patients, with more than one in two patients affected. Multidisciplinary care for TB patients involving mental health practitioners is highly encouraged, especially for high risk groups. PMID- 27268139 TI - Strengthening Purity: Moral Purity as a Mediator of Direct and Extended Cross Group Friendships on Sexual Prejudice. AB - The present research investigated whether enhanced perceptions of moral purity drive the effects of intergroup cross-group friendships on the intentions to interact with homosexuals. High-school students (N = 639) reported their direct and extended cross-group friendships with homosexuals as well as their beliefs regarding the moral character of the sexual minority. Participants further reported their desire to interact with homosexuals in the future. Results showed that both face-to-face encounters and extended contact with homosexuals increased their perceived moral purity, which in turn fostered more positive behavioral intentions. Results further revealed the specific role of moral purity in this sense, as differential perceptions along other moral domains (autonomy and community) had no mediation effects on behavioral tendencies toward homosexuals. The importance of these findings for improving intergroup relations is discussed, together with the importance of integrating research on intergroup contact and morality. PMID- 27268140 TI - Selective Uptake and Refolding of Globular Proteins in Coacervate Microdroplets. AB - Intrinsic differences in the molecular sequestration of folded and unfolded proteins within poly(diallyldimethylammonium) (PDDA)/poly(acrylate) (PAA) coacervate microdroplets are exploited to establish membrane-free microcompartments that support protein refolding, facilitate the recovery of secondary structure and enzyme activity, and enable the selective uptake and exclusion of folded and unfolded biomolecules, respectively. Native bovine serum albumin, carbonic anhydrase, and alpha-chymotrypsin are preferentially sequestered within positively charged coacervate microdroplets, and the unfolding of these proteins in the presence of increasing amounts of urea results in an exponential decrease in the equilibrium partition constants as well as the kinetic release of unfolded molecules from the droplets into the surrounding continuous phase. Slow refolding in the presence of positively charged microdroplets leads to the resequestration of functional proteins and the restoration of enzymatic activity; however, fast refolding results in protein aggregation at the droplet surface. In contrast, slow and fast refolding in the presence of negatively charged PDDA/PAA droplets gives rise to reduced protein aggregation and misfolding by interactions at the droplet surface to give increased levels of protein renaturation. Together, our observations provide new insights into the bottom-up design and construction of self-assembling microcompartments capable of supporting the selective uptake and refolding of globular proteins. PMID- 27268141 TI - p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex. AB - The regulation of transcription by RNA polymerase II (Pol II) is important for a variety of cellular functions. ELL/EAF-containing little elongation complex (LEC) was found to be required for transcription of Pol II-dependent small nuclear RNA (snRNA) genes. It was shown that the tumor suppressor p53 interacts with ELL and inhibits transcription elongation activity of ELL. Here, we show that p53 inhibits interaction between ELL/EAF and ICE1 in LEC and thereby p53 represses transcription of Pol II-dependent snRNA genes through inhibiting LEC function. Furthermore, induction of p53 expression by ultraviolet (UV) irradiation decreases the occupancy of ICE1 at Pol II-dependent snRNA genes. Consistent with the results, knockdown of p53 increased both the expression of snRNA genes and the occupancy of Pol II and components of LEC at snRNA genes. Our results indicate that p53 interferes with the interaction between ELL/EAF and ICE1 and represses transcription of snRNA genes by Pol II. PMID- 27268142 TI - Socioeconomic status and health outcomes: cystic fibrosis as a model. AB - INTRODUCTION: Socioeconomic status (SES), which indicates one's access to financial, educational, and social resources, is a powerful determinant of health outcomes in multiple chronic diseases. Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in a single gene. Although life expectancy and quality of life for patients with CF have improved exponentially, disease severity varies substantially, even among individuals with identical genotypes. AREAS COVERED: CF disease progression and outcomes are influenced by a number of nongenetic factors, such as material well-being, educational attainment, living and working conditions, physical environment and exposures, family environment, social support, health behaviors, and health care. This review discusses pathways by which financial, educational, and social resources are translated into health advantages in CF. Expert commentary: To achieve equitable CF outcomes, the contribution of nongenetic factors must be emphasized, highlighting the mechanisms through which the social and physical environments influence disease variability. PMID- 27268143 TI - Water Sorption Isotherms of Surfactants: A Tool To Evaluate Humectancy. AB - Fundamental experimental data for moisture absorption of non-ionic polydisperse surfactants with differing ethylene oxide (EO) content and variable aliphatic portions were measured at relative humidities between 0 and 95% at 25 degrees C. Remarkable differences in moisture absorption were observed between surfactant classes but also within one series of surfactants differing in either EO content or the long-chain aliphatic fraction. Both the EO units as well as the entire molecular structure, including also the lipophilic domain, were discussed to account for the humectant activity of surfactants. Water sorption isotherms showed an exponential shape, which was argued to be associated with the formation of a "free" water domain. These humectant properties might be relevant to the behavior of a foliar-applied spray droplet of agrochemical formulation products because the uptake of active ingredients will be enhanced as a result of deferred crystal precipitation. PMID- 27268144 TI - Dynamics of ligand binding to GPCR: Residence time of melanocortins and its modulation. AB - Ligand binding dynamics and the concept of drug-target residence time are essential factors in the development of novel drugs. Conventional ligand binding assays, which usually collect end-point data, do not provide abundant information regarding the ligand binding kinetics. Therefore, novel methods that allow on line monitoring of ligand binding processes have to be developed and implemented for drug discovery studies. In this study, we provide a short overview of novel possibilities to characterize ligand binding dynamics to different G protein coupled receptors (GPCRs). Special attention has been paid to the ligand binding to melanocortin 4 receptors and to the development of a fluorescence anisotropy based assay system using receptors in budded baculovirus particles. It has been shown that ligand binding to melanocortin 4 receptors occurs to tandemly arranged interconnecting ligand binding sites and that the conventional equilibrium usually cannot be achieved in this system. Therefore, the apparent potencies of the same ligand may differ by up to four orders of magnitude, depending on the experimental conditions and the reporter ligand used. PMID- 27268146 TI - Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer. AB - Histone modifications play critical roles in the progression of non-small cell lung cancer (NSCLC), which accounts for almost 85% of all diagnosed lung cancers. Magnolol and polyphenol mixture (PM) derived from Magnolia officinalis exhibited remarkable antitumor activities in lung cancer. However, the epigenetic effects and molecular mechanisms of magnolol and PM in NSCLC have yet to be reported. In this study, the epigenetic effects of magnolol and PM in NSCLC were examined in vitro and in vivo. Results revealed that magnolol and PM significantly suppressed the expression levels and function of class I histone deacetylases (HDACs). In A549 and H1299 cells, magnolol and PM remarkably induced cell apoptosis by arresting the cell cycle in the G0/G1 phase while simultaneously activating various pro-apoptotic signals, including TRAIL-R2 (DR5), Bax, caspase 3, cleaved caspase 3, and cleaved PARP. However, these apoptosis-promoting effects could be attenuated by TSA, which is a specific class I HDACs inhibitor. ChIP assays also demonstrated that magnolol and PM significantly enriched the histone acetyl mark (H3K27ac) in the promoter region of DR5. In A549 xenograft model, magnolol and PM notably reduced tumor growth by 44.40% and 35.40%, respectively. Therefore, magnolol and PM, as potential inhibitors of class I HDACs, induced tumor cell apoptosis and suppressed tumor growth partially by epigenetically activating DR5, which is a key protein in death receptor signaling pathway. PMID- 27268147 TI - Multilocus genotyping of Giardia duodenalis isolates from calves in Oromia Special Zone, Central Ethiopia. AB - Giardia duodenalis is a widespread protozoan parasite that infects human and other mammals. Assessing the zoonotic transmission of the infection requires molecular characterization as there is considerable genetic variation within the species. This study was conducted to identify assemblages of Giardia duodenalis in dairy calves; and to assess the potential role of cattle isolates in zoonotic transmission in central Ethiopia. A total of 449 fecal samples were collected and screened using microscopy and PCR targeting the small-subunit (ssu) rRNA, triose phosphate isomerase (tpi), beta-giardin (bg) and glutamate dehydrogenase (gdh) genes. The overall prevalence of Giardia duodenalis in dairy calves was found to be 9.6% (43/449). The prevalence of infection based on sex, age and breed difference was statistically not significant (p>0.05). Genotyping results revealed the presence of assemblage E and assemblage A (AI). The genotypic frequency reported was 95.3% (41/43) for assemblage E and 4.7% (2/43) for assemblage A. There was one mixed infection with assemblages AI and E. Sequence analyses showed the existence of 10 genotypes within assemblage E. One genotype that showed novel nucleotide substitution was identified at the ssu rRNA locus. The other 9 genotypes, 3 at each locus, were identified at the tpi, the bg and the gdh loci with two of the gdh genotypes were novel. Findings of the current study indicate the occurrence of the livestock-specific assemblage E and the potentially zoonotic assemblage A, with the former being more prevalent. Although the zoonotic assemblage was less prevalent, there is a possibility of zoonotic human infection as AI is reported from both animals and humans. PMID- 27268149 TI - The nuclear elongation factor-1alpha gene: a promising marker for phylogenetic studies of Triatominae (Hemiptera: Reduviidae). AB - Molecular systematics is a remarkable approach for understanding the taxonomic traits and allows the exploration of the inter-population dynamics of several species in the Triatominae subfamily that are involved in Trypanosoma cruzi transmission. Compared to other relevant species that transmit vector-borne diseases, such as some species of the Diptera, there are relatively few nuclear genetic markers available for systematic studies in the Triatominae subfamily. Molecular systematic studies performed on Triatominae are based on mitochondrial gene fragments and, less frequently, on nuclear ribosomal genes or spacers. Due to the fact that these markers can occasionally present problems such as nuclear mitochondrial genes (NUMTs) or intra-genomic variation for high gene copy numbers, it is necessary to use additional nuclear markers to more reliably address the molecular evolution of Triatominae. In this study, we performed phylogenetic analysis using the nuclear elongation factor-1 alpha (EF-1alpha) gene in individuals from 12 species belonging to the Triatomini and Rhodniini tribes. Genetic diversities and phylogenetic topologies were compared with those obtained for the mitochondrial 16S rRNA and Cytochrome b (cyt b) genes, as well as for the D2 variable region of the ribosomal 28S rRNA gene. These results indicate that the EF-1alpha marker exhibits an intermediate level of diversity compared to mitochondrial and nuclear ribosomal genes, and that phylogenetic analysis based on EF-1alpha is highly informative for resolving deep phylogenetic relationships in Triatominae, such as tribe or genera. PMID- 27268148 TI - CD8(+) T cells specific to a single Yersinia pseudotuberculosis epitope restrict bacterial replication in the liver but fail to provide sterilizing immunity. AB - CD8(+) T cells use contact-dependent cytolysis of target cells to protect the host against intracellular pathogens. We have previously shown that CD8(+) T cells and perforin are required to protect against the extracellular pathogen Yersinia pseudotuberculosis. Here we establish an experimental system where CD8(+) T cells specific to a single model antigen are the only memory response present at time of challenge. Using mice immunized with a vaccine strain of Listeria monocytogenes that expresses secreted ovalbumin (Lm-OVA), we show that OVA-specific CD8(+) T cells are generated and provide limited protection against challenge with virulent OVA(+)Y. pseudotuberculosis. Perforin expression by OVA specific CD8(+) T cells was required, as Lm-OVA-immunized perforin-deficient mice showed higher bacterial burden as compared to Lm-OVA-immunized perforin sufficient mice. Surprisingly, antigen-specific T cell protection waned over time, as Lm-OVA-immune mice eventually succumbed to Yersinia infection. Kinetic analysis of infection in mice with and without OVA-specific CD8(+) T cells revealed that bacterial numbers increased sharply in OVA-naive mice until death, while OVA-immune mice held bacterial burden to a lower level throughout the duration of illness until death. Clonal analysis of bacterial populations in OVA naive and OVA-immune mice at distinct time points revealed equivalent and severe bottle-neck effects for bacteria in both sets of mice immediately after intravenous challenge, demonstrating a dominant role for other aspects of the immune system regardless of CD8(+) T cell status. These studies indicate that CD8(+) T cells against a single antigen can restrict Y. pseudotuberculosis colonization in a perforin-dependent manner, but ultimately are insufficient in their ability to provide sterilizing immunity and protect against death. PMID- 27268145 TI - PPARgamma signaling and emerging opportunities for improved therapeutics. AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand activated nuclear receptor that regulates glucose and lipid metabolism, endothelial function and inflammation. Rosiglitazone (RGZ) and other thiazolidinedione (TZD) synthetic ligands of PPARgamma are insulin sensitizers that have been used for the treatment of type 2 diabetes. However, undesirable side effects including weight gain, fluid retention, bone loss, congestive heart failure, and a possible increased risk of myocardial infarction and bladder cancer, have limited the use of TZDs. Therefore, there is a need to better understand PPARgamma signaling and to develop safer and more effective PPARgamma directed therapeutics. In addition to PPARgamma itself, many PPARgamma ligands including TZDs bind to and activate G protein-coupled receptor 40 (GPR40), also known as free fatty acid receptor 1. GPR40 signaling activates stress kinase pathways that ultimately regulate downstream PPARgamma responses. Recent studies in human endothelial cells have demonstrated that RGZ activation of GPR40 is essential to the optimal propagation of PPARgamma genomic signaling. RGZ/GPR40/p38 MAPK signaling induces and activates PPARgamma co-activator-1alpha, and recruits E1A binding protein p300 to the promoters of target genes, markedly enhancing PPARgamma-dependent transcription. Therefore in endothelium, GPR40 and PPARgamma function as an integrated signaling pathway. However, GPR40 can also activate ERK1/2, a proinflammatory kinase that directly phosphorylates and inactivates PPARgamma. Thus the role of GPR40 in PPARgamma signaling may have important implications for drug development. Ligands that strongly activate PPARgamma, but do not bind to or activate GPR40 may be safer than currently approved PPARgamma agonists. Alternatively, biased GPR40 agonists might be sought that activate both p38 MAPK and PPARgamma, but not ERK1/2, avoiding its harmful effects on PPARgamma signaling, insulin resistance and inflammation. Such next generation drugs might be useful in treating not only type 2 diabetes, but also diverse chronic and acute forms of vascular inflammation such as atherosclerosis and septic shock. PMID- 27268150 TI - High-throughput sequencing of microbial diversity in implant-associated infection. AB - Few molecular studies have shown that the number of bacterial species in implant associated infection may have been underestimated. To determine the actual microbial diversity in implant-associated infection, a high-throughput sequencing method was adopted to sequence the DNAs extracted from the tissues of infected and uninfected patients. Principal component analysis (PCA) and beta diversity showed an obvious divergence of infected and uninfected groups, and that the overgrowth of Proteobacteria (80.87%), Firmicutes (13.41%) in the positive deep infection group (P.d, via biopsy) and Proteobacteria (91.68%) in the positive surface infection group (P.s, via swabs) might be the causative factors in implant-associated infection. Moreover, Venn results indicated that a mean of 330 common operational taxonomic units (OTUs) was obtained in all groups, of which 113, 109, 45, 20, 13 and 12 OTUs belonging to Proteobacteria, Actinobacteria, Acidobacteria, Planctomycetes, Gemmatimonadetes and Chloroflexi were identified. In conclusion, many traditional "pathogenic bacteria" were identified as the common bacteria in operation sites, and the disruption of their complex interaction caused infection; therefore, further work is need to illustrate the aetiology of implant-associated infection using in-depth systems-level analyses. PMID- 27268151 TI - Molecular epidemiology of human cutaneous leishmaniasis in Jericho and its vicinity in Palestine from 1994 to 2015. AB - Cutaneous leishmaniases (CL) are vector-borne parasitic diseases endemic in many countries of the Middle East including Palestine. Between 1994 and 2015, 2160 clinically suspected human cases of CL from the Jericho District were examined. Stained skin tissue smears and aspirates were checked by microscopy and cultured for promastigotes, respectively. For leishmanial species identification, amplification products from a PCR-ITS1 followed by RFLP analysis using Hae III. Data were analyzed using Epi Info free-software. The overall infection rate was 41.4% (895/2160), 56.3% (504/895) of the cases were male, 43.7% (391/895) female, 60.5% (514/849) children under age 14, 41.3% (259/627) of the cases were caused by Leishmaniamajor and 57.3% (359/627) by Leishmaniatropica. The case numbers peaked in 1995, 2001, 2004, and 2012. Statistically-significant clusters of cases caused by L. major were restricted to the Jericho District; those caused by L. tropica were from the districts of Jericho, Bethlehem, Nablus and Tubas. CL is seasonal and trails the sand fly season. Distribution of cases was parabolic with fewest in July. The monthly total number of cases of CL and just those caused by L. major correlated significantly with temperature, rainfall, relative humidity, evaporation, wind speed and sunshine (P<0.05, r2=0.7-0.9 and P<0.05, r2=0.5-0.8, respectively). Cases caused by L. tropica, significantly, had a single lesion compared to cases caused by L. major (P=0.0001), which, significantly, had multiple lesions (P=0.0001). This and previous studies showed that CL is present in all Palestinian districts. The surveillance of CL has increased public awareness and molecular biological methodology for leishmanial species identification is an essential addition to classical diagnosis. The overall results are discussed, correlated to climatic and environmental changes and large scale human activities. PMID- 27268152 TI - Redox-Innocent Metal-Assisted Cleavage of S-S Bond in a Disulfide-Containing Ligand. AB - Due to their redox capabilities, thiols have an important role in biological oxidative/reductive processes through the formation of disulfides or their oxidation to into sulfenic, sulfinic, or sulfonic derivatives being also relevant for specific enzyme activities. The mechanisms of these biological pathways often involve metal ion(s). In this case, deciphering metal-assisted transformation of the S-S bond is of primary interest. This report details the reactivity of the disulfide-containing 2,6-bis[(bis(pyridylmethyl)amino)methyl]-4 methylmercaptophenyldisulfide (L(Me(BPA)S-S)) ligand with Cu(II) using different experimental conditions (anaerobic, H2O-only, H2O/O2, or O2-only). Crystallographic snapshots show the formation of tetranuclear disulfide, dinuclear sulfinate, and sulfonate complexes. Mechanistic investigations using Zn(II) as control indicate a non-metal-redox-assisted process in all cases. When present, water acts as nucleophile and attacks at the S-S bond. Under anhydrous conditions, a different pathway involving a direct O2 attack at the disulfide is proposed. PMID- 27268153 TI - Measuring spatial equity and access to maternal health services using enhanced two step floating catchment area method (E2SFCA) - a case study of the Indian Sundarbans. AB - INTRODUCTION: Inaccessibility due to terrain and lack of transport leaves mothers travelling for long hours before reaching a facility to deliver a child. In the present article we analyzed the issue of spatial inaccessibility and inequity of maternal health services in the Indian Sundarbans where complex topography and repeated climatic adversities make access to health services very difficult. METHODS: We based the article on the health-GIS study conducted in the Patharpratima Block of the Sundarbans in the year 2012. The region has 87 villages that are inhabited, of which 54 villages are in the deltaic (river locked) region and 33 villages are located in the non-deltaic region of the block. We mapped all public and private maternal health facilities and road and water transport network. For measuring inaccessibility, we use the enhanced two step floating catchment area method (E2SFCA). For assessing inequity in spatial access, we developed an area-based socioeconomic score and constructed a concentration curve to depict inequity. We used ARC GIS 10.3.1 and Stata 11 software for our analysis. RESULTS: The maternal health facilities are primarily located in the non-deltaic region of the block. On an average it takes 33.81 min to reach the closest maternal health facility. Fifty-two villages out of eighty seven villages have access scores less than the score calculated using Indian Primary Health Standards. Ten villages cannot access any maternal health facility; twenty-six villages have access scores of less than one doctor for 1000 pregnant women; fifty-six villages have access scores less than the block average of 3.54. The access scores are lower among villages in the deltaic region compared to the non-deltaic region. The concentration curve is below the line of equality showing that access scores were lower among villages that were socio economically disadvantaged. CONCLUSIONS: Maternal health facilities are not equitably accessible to the populations that are disadvantaged and living in the remote pockets of the study region. Provision of a referral transport system along with a resilient infrastructure of roads is critical to improve access in these islands. PMID- 27268154 TI - The Vanishing Twin Syndrome: Two cases of extreme malformations associated with vanished twins. AB - Two cases of devastating fetal malformations associated with vanished monochorionic twins were identified upon review of pathology files. A 35 year-old G1P0 woman and 36 year-old G3P1 woman were both diagnosed with an intrauterine twin gestation via transvaginal ultrasound at 10 weeks. The spectrum of fetal anomalies ranged from omphalocele, bilateral upper extremity and unilateral lower extremity hypoplasia, to craniofacial malformation with diaphragmatic hernia. On histopathologic examination, the placentas demonstrated vascular anastomoses between the surviving co-twin and the "vanished" fetal sac. We propose anastomotic placental vasculature as a contributing factor to the observed fetal malformations. Additionally, genetic or teratogenic factors may have been attributed to the demise of the first twin and the anomalies seen in the other twin. While such instances are rare, they are important to consider when counseling patients regarding outcomes associated with a monochorionic vanished twin. PMID- 27268155 TI - RetroDISCO: Clearing technique to improve quantification of retrograde labeled motor neurons of intact mouse spinal cords. AB - BACKGROUND: Quantification of the number of axons reinnervating a target organ is often used to assess regeneration after peripheral nerve repair, but because of axonal branching, this method can overestimate the number of motor neurons regenerating across an injury. Current methods to count the number of regenerated motor neurons include retrograde labeling followed by cryosectioning and counting labeled motor neuron cell bodies, however, the process of sectioning introduces error from potential double counting of cells in adjacent sections. NEW METHOD: We describe a method, retroDISCO, that optically clears whole mouse spinal cord without loss of fluorescent signal to allow imaging of retrograde labeled motor neurons using confocal microscopy. RESULTS: Complete optical clearing of spinal cords takes four hours and confocal microscopy can obtain z-stacks of labeled motor neuron pools within 3-5min. The technique is able to detect anticipated differences in motor neuron number after cross-suture and conduit repair compared to intact mice and is highly repeatable. COMPARISON WITH EXISTING METHOD: RetroDISCO is inexpensive, simple, robust and uses commonly available microscopy techniques to determine the number of motor neurons extending axons across an injury site, avoiding the need for labor-intensive cryosectioning and potential double counting of motor neuron cell bodies in adjacent sections. CONCLUSIONS: RetroDISCO allows rapid quantification of the degree of reinnervation without the confounding produced by axonal sprouting. PMID- 27268157 TI - Surveillance systems and methods for monitoring the post-marketing safety of influenza vaccines at the Centers for Disease Control and Prevention. AB - INTRODUCTION: Annual influenza vaccine safety monitoring is an important component of the influenza vaccination program in the United States to ensure that vaccines are safe, which is important for maintaining public trust in the national vaccination program. This is specially the case for influenza vaccines since the antigen composition of the viruses of which the vaccine is made often changes from one season to the next, based on the circulating strain of influenza virus. AREAS COVERED: This review describes the two surveillance systems used by the Centers for Disease Control and Prevention (CDC) to monitor the safety of influenza vaccines: 1) the Vaccine Adverse Event Reporting System (VAERS); and 2) the Vaccine Safety datalink (VSD). EXPERT OPINION: VAERS and VSD are used routinely to monitor the safety of influenza vaccines in the United States, and over the years they have demonstrated their value in monitoring vaccine safety since their implementation in 1990. Both systems, although different, complemented each other well to study febrile seizures in young children following influenza vaccination during the 2010-2011 influenza season. Other examples of potential safety concerns after influenza vaccines are also presented and discussed. PMID- 27268156 TI - A linear model for event-related respiration responses. AB - BACKGROUND: Cognitive processes influence respiratory physiology. This may allow inferring cognitive states from measured respiration. Here, we take a first step towards this goal and investigate whether event-related respiratory responses can be identified, and whether they are accessible to a model-based approach. NEW METHOD: We regard respiratory responses as the output of a linear time invariant system that receives brief inputs after psychological events. We derive average responses to visual targets, aversive stimulation, and viewing of arousing pictures, in interpolated respiration period (RP), respiration amplitude (RA), and respiratory flow rate (RFR). We then base a Psychophysiological Model (PsPM) on these averaged event-related responses. The PsPM is inverted to yield estimates of cognitive input into the respiratory system. This method is validated in an independent data set. RESULTS: All three measures show event related responses, which are captured as non-zero response amplitudes in the PsPM. Amplitude estimates for RA and RFR distinguish between picture viewing and the other tasks. This pattern is replicated in the validation experiment. COMPARISON WITH EXISTING METHODS: Existing respiratory measures are based on relatively short time-intervals after an event while the new method is based on the entire duration of respiratory responses. CONCLUSION: Our findings suggest that interpolated respiratory measures show replicable event-related response patterns. PsPM inversion is a suitable approach to analysing these patterns, with a potential to infer cognitive processes from respiration. PMID- 27268158 TI - Teaching and preschoolers' ability to infer knowledge from mistakes. AB - For instruction to be effective, teachers must adjust the way they teach to match what learners know. We asked whether children's ability to infer what someone knows based on his or her mistakes develops alongside their teaching-children's use of more explicit teaching strategies and their ability to tailor how much information to provide in response to their pupils' mistakes. Preschoolers (N=48) were taught a simple game and were then introduced to four puppets: one puppet who played the game perfectly, two puppets who each made one mistake, and one puppet who made two mistakes. After watching each puppet play individually, children were asked to rate the puppet's understanding of the game and then were invited to teach the puppet. Children's ability to monitor the relative accuracy of the puppets-the ability to make nuanced judgments about what each puppet understood based on each puppet's unique mistakes-improved with age. Moreover, older children were more explicit and more precise teachers than younger children. They more often contrasted the learners' mistakes with what should be done and more often provided instructions that directly addressed the puppets' unique mistakes. Thus, between 3 and 5 years of age, developments in children's ability to infer knowledge from mistakes parallel developments both in the strategies children use to teach and in the amount of information they teach in response to mistakes. PMID- 27268159 TI - Children's generic interpretation of pretense. AB - We report two experiments investigating how 3- to 5-year-olds learn general knowledge from pretend play-how they learn about kinds of things (e.g., information about dogs) from information about particular individuals in pretend play (a certain dog in a pretend scenario). Children watched pretend-play enactments in which animals showed certain behaviors or heard utterances conveying the same information. When children were subsequently asked about who shows the behavior, children who watched pretend play were more likely to give generic responses than were children who heard the utterances. These findings show that children generalize information from pretend play to kinds even without being prompted to think about kinds, that pretend play can be informative about familiar kinds, and also that pretend play is a more potent source for general knowledge than are utterances about individuals. PMID- 27268160 TI - Twelve possible strategies for enhancing interprofessional socialisation in higher education: Findings from an interpretive phenomenological study. AB - The aim of this study was to investigate the interprofessional socialisation experiences of health professional educators (HPEs) across five health science faculties in Perth, Australia. Evidence supported the importance of educators teaching and learning together, although there was minimal evidence with regard to the type of support HPEs received or required in order to socialise interprofessionally within higher education. Interview participants comprised 26 HPEs from various health-related professions across Western Australia. An interpretive phenomenological framework was used to discover the phenomena of interprofessional socialisation. The examination of the data was undertaken via qualitative content analysis with the aid of NVivo 10 software. Content coding led to the development of categories, sub-categories, and then themes. Five themes were identified; however, only one of these themes, "interprofessional socialisation strategies within higher education," is explored within this article. Based on the data within this theme, 12 possible socialisation strategies (formal and informal) were identified for HPEs, which could be implemented within health science faculties, taking into account the organisation's culture and strategic intent towards interprofessional collaboration and education. PMID- 27268161 TI - Enantioselective Synthesis of Polysubstituted Spiro-nitroprolinates Mediated by a (R,R)-Me-DuPhos.AgF-Catalyzed 1,3-Dipolar Cycloaddition. AB - The synthesis of constrained spirocycles is achieved effectively by means of 1,3 dipolar cyclodditions employing alpha-imino gamma-lactones as azomethine ylide precursors and nitroalkenes as dipolarophiles. The complex formed by (R,R)-Me DuPhos 18 and AgF is the most efficient bifunctional catalyst. Final spiro nitroprolinates cycloadducts are obtained in good to moderate yields and both high diastereo- and enantioselectivities. Density functional theory (DFT) calculations supported the expected absolute configuration as well as other stereochemical parameters. PMID- 27268162 TI - Perfluoroalkyl and polyfluoroalkyl substances and measures of human fertility: a systematic review. AB - Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found widespread in the environment and humans. The relation of PFASs to fertility has now been examined in a relatively large number of epidemiologic studies and a synthesis is in order. The aim of this study was to assess the current human epidemiologic evidence on the association between exposure to PFASs and measures of human fertility, with particular emphasis on perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA). Systematic literature searches were initially conducted in MEDLINE and EMBASE and subsequently in references and citations of included papers. Studies were included if they assessed exposure to PFASs in biological samples in relation to reproductive hormones, semen characteristics, or time to pregnancy (TTP). Study characteristics and results were abstracted to predefined forms, and the studies were assessed for the risk of bias and confounding. Sixteen studies investigated the association between PFAS exposure in men and semen parameters, reproductive hormone levels, or TTP. There was a lack of consistent results among the numerous investigated exposure-outcome combinations. However, subtle associations between higher PFOS and lower testosterone or abnormal semen morphology cannot be excluded. Eleven studies assessed the association between PFAS exposure in women and TTP or reproductive hormones levels. Four of eight studies found prolonged TTP with higher PFOS or PFOA, but only one study found an association when restricting to nulliparous women. In men, there is little evidence of an association between PFAS exposure and semen quality or levels of reproductive hormones. For PFOS and PFOA, the literature indicates an association with female fecundability in parous women, which is most likely not causal. PMID- 27268163 TI - Semi-continuous ultrasonic sounding and changes of ultrasonic signal characteristics as a sensitive tool for the evaluation of ongoing microstructural changes of experimental mortar bars tested for their ASR potential. AB - Semi-continuous ultrasonic sounding of experimental mortar bars used in the accelerated alkali silica reactivity laboratory test (ASTM C1260) is proposed as a supplementary measurement technique providing data that are highly sensitive to minor changes in the microstructure of hardening/deteriorating concrete mixture. A newly designed, patent pending, heating chamber was constructed allowing ultrasonic sounding of mortar bars, stored in accelerating solution without necessity to remove the test specimens from the bath during the measurement. Subsequent automatic data analysis of recorded ultrasonic signals proved their high correlation to the measured length changes (expansion) and their high sensitivity to microstructural changes. The changes of P-wave velocity, and of the energy, amplitude, and frequency of ultrasonic signal, were in the range of 10-80%, compared to 0.51% change of the length. Results presented in this study thus show that ultrasonic sounding seems to be more sensitive to microstructural changes due to ongoing deterioration of concrete microstructure by alkali-silica reaction than the dimensional changes. PMID- 27268164 TI - Spatial averaging effects of hydrophone on field characterization of planar transducer using Fresnel approximation. AB - The purpose of this work was to improve the existing models that allow spatial averaging effects of piezoelectric hydrophones to be accounted for. The model derived in the present study is valid for a planar source and was verified using transducers operating at 5 and 20MHz. It is based on Fresnel approximation and enables corrections for both on-axis and off-axis measurements. A single-integral approximate formula for the axial acoustic pressure was derived, and the validity of the Fresnel approximation in the near field of the planar transducer was examined. The numerical results obtained using 5 and 20MHz planar transmitters with an effective diameter of 12.7mm showed that the derived model could account for spatial averaging effects to within 0.2% with Beissner's exact integral (Beissner, 1981), for k(a+b)2?pi (where k is the circular wavenumber, and a and b are the effective radii of the transmitter and hydrophone, respectively). The field distributions along the acoustic axis and the beam directivity patterns are also included in the model. The spatial averaging effects of the hydrophone were generally observed to cause underestimation of the absolute pressure amplitudes of the acoustic beam, and overestimation of the cross-sectional size of the beam directivity pattern. However, the cross-sectional size of the directivity pattern was also found to be underestimated in the "far zone" (beyond Y0=a(2)/lambda) of the transmitter. The results of this study indicate that the spatial averaging effect on the beam directivity pattern is negligible for pi(gamma(2)+4gamma)s?1 (where gamma=b/a, and s is the normalized distance to the planar transducer). PMID- 27268201 TI - Factors influencing diagnosis delay of advanced breast cancer in Moroccan women. AB - BACKGROUND: Delay in the diagnosis of breast cancer in symptomatic women of 3 months or more is associated with advanced stage and low survival. We conducted this study to learn more about the extent and reasons behind diagnosis delay of advanced breast cancer in Moroccan women. METHODS: A group of patients with advanced breast cancer were interviewed at the National Institute of Oncology in Rabat during the period from February to December 2014. Diagnosis delay was devised into patient delay and system delay. Patient delay was defined as time from first symptoms until first medical consultation. System delay was defined as time from first presentation to a health care provider until definite diagnosis or treatment. Prospective information and clinical data were collected on a form during an interview with each patient and from medical records. RESULTS: In all, 137 patients were interviewed. The mean age of women was 48.3 +/- 10.4 years. The median of consultation time was 6[4,12] months and the median of diagnosis time was 1[1,3] months. Diagnosis delay was associated to a personal reason in 96 (70.1 %) patients and to a medical reason in 19 (13.9 %) patients. A number of factors predicted diagnosis delay: symptoms were not considered serious in 66 (55.9 %) patients; traditional therapy was applied in 15 (12.7 %) patients and fear of cancer diagnosis and/or treatment in 14 (11.9 %) patients. A use of traditional methods was significantly associated with rural residence and far away from basic health center (p = 0.000). Paradoxically, a family history of breast cancer was significantly higher in who report a fear of cancer diagnosis and/or treatment to diagnosis delay (p < 0.001). Also, a significantly higher risk of more than 6 months delay was found among rural women (P = 0.035) and women who live far away from specialized care center (P = 0.001). CONCLUSIONS: Diagnosis delay is very serious problem in Morocco. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer information in our populations and training of general practitioners to reduce advanced breast cancer by promoting early detection. PMID- 27268202 TI - Authors' reply to Cunningham and Messerli and colleagues. PMID- 27268203 TI - Increased ADMA levels are associated with poor pulmonary outcome in preterm neonates. AB - BACKGROUND: Nitric oxide (NO), synthesized from the amino acid L-arginine by the action of NO synthases (NOS), is a pulmonary vasodilator. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. Preterm infants have higher plasma ADMA concentrations than term infants which could cause inhibition of NO synthesis and deterioration in pulmonary functions. We aimed to investigate the relationship between serum ADMA and L-arginine levels of preterm infants and respiratory distress syndrome (RDS), requirement of surfactant treatment, duration of mechanical ventilation, oxygen treatment, and development of bronchopulmonary dysplasia (BPD). METHODS: A prospective cohort study was conducted including 80 preterm infants born with gestational age (GA) <= 32 weeks and birth weight (BW) <= 1500 g. Blood samples were obtained from all infants immediately after birth, and at postnatal 28th day of age. The relationship of first-day serum ADMA and L-arginine levels and surfactant requirement, duration of mechanical ventilation, oxygen treatment was investigated. Serum ADMA and L arginine levels at 1st and 28th days were compared at patients with and without BPD. The role of serum ADMA levels at postnatal 28th day of age to predict the requirement of oxygen at postmenstrual 36 weeks of age was also investigated. RESULTS: Eighty preterm infants (42 male, 38 female) were enrolled in the study. Mean BW and GA for the total cohort was 1144.81 +/- 220.44 g and 28.3 +/- 1.8 weeks, respectively. Sixty-one infants were diagnosed as RDS and 44 infants treated with surfactant. The first-day ADMA levels were significantly higher in infants with surfactant requirement (1.14 +/- 0.23 versus 0.86 +/- 0.37, p < 0.01). First-day L-arginine levels were lower in infants with surfactant requirement compared to infants without surfactant requirement (22.32 +/- 2.33 versus 23.75 +/- 2.42, p > 0.05) but not significantly. Serum ADMA and L-arginine concentrations at first day were not different among infants with and without BPD (p > 0.05). ADMA concentrations at 28th day was significantly higher in infants with BPD (1.00 +/- 0.25 versus 0.81 +/- 0.25, p < 0.05). The cutoff level of 0.875 MUmol/L for ADMA at 28th day offered the best predictive value for oxygen requirement at postnatal 36 weeks of age with a sensitivity of 88% and a specificity of 54%. Conclusion: Serum ADMA and L-arginine levels are related to pulmonary morbidities in newborn. The results of this study show that increased ADMA levels are associated with poor pulmonary outcomes in preterm infants. PMID- 27268204 TI - Targeted epigenetic repression of a lymphoma oncogene by sequence-specific histone modifiers induces apoptosis in DLBCL. AB - Alterations to the epigenetic landscape of diffuse large B-cell lymphoma (DLBCL) play a fundamental role in deregulating genes involved in normal lymphocyte differentiation. To determine whether targeted epigenetic therapy could reverse these pathogenic chromatin changes and suppress the expression of a lymphoma oncogene, we focused on BCL6, a transcriptional repressor whose aberrant expression is tightly linked to DLBCL proliferation and survival. We fused zinc finger (ZF) domains specific for regulatory regions in the BCL6 locus to a repressive epigenetic modifier, the Kruppel-associated box (KRAB) repressor domain. Distinct ZF-KRAB fusions repressed the local chromatin landscape, suppressed BCL6 expression, significantly impaired DLBCL growth, and caused widespread cell death in a BCL6-dependent manner. Importantly, expression of ectopic BCL6 protein rescued ZF-KRAB-induced cell death, demonstrating the modifiers' specificity. We show that sequence-specific epigenetic modifiers can alter oncogene expression and induce apoptosis in cancer cells, underscoring their potential for future development as targeted epigenetic protein therapies. PMID- 27268205 TI - The SBOL Stack: A Platform for Storing, Publishing, and Sharing Synthetic Biology Designs. AB - Recently, synthetic biologists have developed the Synthetic Biology Open Language (SBOL), a data exchange standard for descriptions of genetic parts, devices, modules, and systems. The goals of this standard are to allow scientists to exchange designs of biological parts and systems, to facilitate the storage of genetic designs in repositories, and to facilitate the description of genetic designs in publications. In order to achieve these goals, the development of an infrastructure to store, retrieve, and exchange SBOL data is necessary. To address this problem, we have developed the SBOL Stack, a Resource Description Framework (RDF) database specifically designed for the storage, integration, and publication of SBOL data. This database allows users to define a library of synthetic parts and designs as a service, to share SBOL data with collaborators, and to store designs of biological systems locally. The database also allows external data sources to be integrated by mapping them to the SBOL data model. The SBOL Stack includes two Web interfaces: the SBOL Stack API and SynBioHub. While the former is designed for developers, the latter allows users to upload new SBOL biological designs, download SBOL documents, search by keyword, and visualize SBOL data. Since the SBOL Stack is based on semantic Web technology, the inherent distributed querying functionality of RDF databases can be used to allow different SBOL stack databases to be queried simultaneously, and therefore, data can be shared between different institutes, centers, or other users. PMID- 27268206 TI - Nonstructural protein 11 (nsp11) of porcine reproductive and respiratory syndrome virus (PRRSV) promotes PRRSV infection in MARC-145 cells. AB - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) induces one of most important devastating disease of swine worldwide, and the current methods poorly control it. Previous studies have indicated that the nonstructural protein 11 (nsp11) of PRRSV may be an important protein for the immune escape of PRRSV. RESULTS: Here, we firstly explored the effect of over-expression of nsp11 on PRRSV infection and found that over-expression of nsp11 enhanced the PRRSV titers while the small interfering RNA (siRNAs) specifically targeting nsp11 could reduce the PRRSV titers in MARC-145 cells. CONCLUSION: In conclusion, PRRSV nsp11 promotes PRRSV infection in MARC-145 cells and siRNAs targeting nsp11 may be a potential therapeutic strategy to control PRRSV in future. PMID- 27268208 TI - Public Pressure, Private Protest: Illness Narratives of West Indian Immigrants in Montreal with Medically Unexplained Symptoms. AB - Some evidence suggests that West Indian immigrants in Canada are a marginalized and over-burdened group. However, little attention has been given to examining health status and beliefs. We partly redress this gap by investigating health beliefs of West Indian immigrants in Montreal with somatic, emotional, or medically unexplained symptoms. The overall aim was to elicit and explore illness narratives, explanatory models, symptom-attribution and help-seeking in the community. A sample of 15 West Indian immigrants took part in semi-structured interviews. We found that participants overwhelmingly ascribed their symptoms to post-migratory experience. They particularly highlighted the importance of two related factors: chronic overwork since migration and irregular patterns of daily living. Many worked long hours, including overtime and moonlighting. Participants related their irregular patterns of daily living to disturbances of bodily functions (e.g., sleeping, eating) as well as to social functions (e.g., family life). These themes reflected elements of ethno-physiological beliefs common in the West Indies, as well as North American illness models. Attributing medically unexplained symptoms to overwork and irregularity in personal and social realms may be a socially acceptable way of critiquing perceived injustices in participants' work, social and interpersonal situations. This is especially so because the dominant discourse regarding race and ethnicity in Canada tends to emphasize positive aspects of multiculturalism-only reluctantly acknowledging conflict and inequality. Narratives could be interpreted as an oblique criticism of Canadian society's apparent indifference to participants' ongoing marginalization. PMID- 27268207 TI - Protozoa lectins and their role in host-pathogen interactions. AB - Lectins are proteins/glycoproteins of non-immune origin that agglutinate red blood cells, lymphocytes, fibroblasts, etc., and bind reversibly to carbohydrates present on the apposing cells. They have at least two carbohydrate binding sites and their binding can be inhibited by one or more carbohydrates. Owing to carbohydrate binding specificity of lectins, they mediate cell-cell interactions and play role in protozoan adhesion and host cell cytotoxicity, thus are central to the pathogenic property of the parasite. Several parasitic protozoa possess lectins which mediate parasite adherence to host cells based on their carbohydrate specificities. These interactions could be exploited for development of novel therapeutics, targeting the adherence and thus helpful in eradicating wide spread of protozoan diseases. The current review highlights the present state knowledge with regard to protozoal lectins with an emphasis on their haemagglutination activity, carbohydrate specificity, characteristics and also their role in pathogenesis notably as adhesion molecules, thereby aiding the pathogen in disease establishment. PMID- 27268209 TI - In the Presence of Biomedicine: Ayurveda, Medical Integration and Health Seeking in Mysore, South India. AB - This paper is based on a research on medical integration and health seeking in Mysore, South India. It explores the use of Ayurvedic services, the impact of biomedicine on Ayurvedic practices and the meaning of instruments with respect to the expectations of patients and healers. The research was done during 2002 and 2003. The empirical data are derived from interviews, participant observation and survey material. Participant observation was carried out in two hospitals and nine clinics offering Ayurvedic services; 25 Ayurvedic practitioners and 30 patients were interviewed. A total of 233 respondents were surveyed in the University of Mysore and on trains and buses between Mysore and Bangalore. Results suggest that Ayurvedic medicine serves as a health reserve in urban Mysore. For the majority of informants biomedical treatment was an obvious choice of treatment, a form of therapy that was taken for granted, if compared with the preference for Ayurvedic services, which were usually utilized because of the failure of biomedicine. Regarding the position of Ayurveda, three issues are vital: first, the lack of experience and first-hand knowledge of Ayurveda on the part of health seekers, secondly, the significance of instruments, tools and technology as regards the expectations of proper consultation, and thirdly, the impact of medical integration, which seems to be critical for modern Ayurveda to thrive in the health market. In short, in order to gain popularity in an urban context, Ayurvedic practitioners favour institutional integration and adoption of items and practices particular to biomedicine. PMID- 27268210 TI - Taking Traditional Knowledge to the Market: The Commoditization of Indian Medicine. AB - Although for over a century Ayurvedic and Unani manufacturers have played a crucial role in the modernization of Indian medicine and influenced the way Indians look upon their medical traditions, this fact has been largely ignored by social scientists and historians working on Indian medicine. By looking through the lens of the industry and focusing on medicines, this study questions the notion that traditional medicine is largely beyond commerce and is highly sensitive to patients as individual subjects. The paper asks how the logic of the market has shaped, constrained and transformed two Indian medical traditions: Ayurvedic and Unani Tibb. What kind of indigenous medicines dominate the Indian market? To whom are these marketed and what are the images used by the industry to promote their products? How do large manufacturers construct the 'Indianness' of their commodities? Based on ethnographic research among large Ayurvedic and Unani manufacturers in India during the period 1996-2002, data for this paper was generated from open-ended interviews, conversations, observations, and company publications such as popular and semi-popular periodicals. Promotional materials and research reports were also used, as well as popular writings on Indian medicine such as articles in general newspapers and magazines. The paper concludes with a discussion of the effects of commoditization of Ayurvedic and Unani medicines for clinical practice and the consequences of this development for the poorer sections of Indian society. The paper highlights Indian medicine as a commercial activity. PMID- 27268211 TI - Maintaining the Balance in a Juvenile Diabetic Clinic. AB - A paediatric diabetic clinic is described by a child psychiatrist, using a series of models from within and outside child psychiatry: biochemical, behavioural, systemic and cultural. Descriptions pivoted around the term, balance. 'Balance' is seen as a metaphor that structured the author's understanding of the dilemmas faced by the participants. The paper then places this meaning-based approach in the context of power: power over resources, authority over knowledge and responsibility for others. The clinic is understood as an ongoing interchange between meaning- and power-based views. The claim is that liaison child psychiatry needs cultural or anthropological approaches to appreciate the complexities of everyday medical work. PMID- 27268212 TI - Beliefs and Traditions Related to a Child's First Year of Life: A Study of the North-west of Portugal. AB - In this paper we propose an approach to investigate, in the North-west of Portugal, the parents' behaviour at birth and during the first year of life of their children. We compare the heritage, specifically the beliefs and traditions, with the changes that resulted from the recent and deep cultural transformations that have taken place in Portugal in the last few decades. In parallel, we tried to determine if the parents' behaviours, based on beliefs and traditions, can affect the children's health. We based our investigation on standardized interviews with 76 mothers of one-year-old children (born between January and December 2001) who lived in two parishes of Vizela city. This is a territory where a more traditional way of life prevails than in other territories of the centre and south of the country, where there is a strong attachment for religious and social values and where the influence of the ancestral traditions is still alive. The paper concludes that cultural heritage can have important impact on individual health. Health professionals, who work in primary care and in hospitals, must be aware of the responsibility they have to change this scenario. PMID- 27268213 TI - The Age of Anxiety: Stones, Feathers and Re-institutionalization. AB - Although the value of the Italian psychiatric reform is widely acknowledged and hotly contested, a meticulous comment on its roots and progress is required. This paper attempts to examine the current state of mental health services in Italy and emphasizes Franco Basaglia's writings. The aim of the paper is to: (1) respond to the challenge of providing adequate and human rights-based mental health services, (2) contrast the new Italian tendency of medicalization, which is supported by a law proposal to re-institutionalize the mental health care system. The analysis is based on both current and historical library work and literature review. Since the present policy seems to be proceeding backwards, the direct study of Basaglia's writings assumes significance in not forgetting the past as well as in re-interpreting the present risk of re-institutionalization. The paper then emphasizes the veracity of Basaglia's thought and suggests a re reading of his work. PMID- 27268214 TI - Los Naturistas-Healers Who Integrate Traditional and Biomedical Explanations in Their Treatment in the Bolivian Health Care System. AB - Medical pluralism is a common feature in most health care systems. In this system integration and exchanges between sectors are common, thus forming complex and hybrid systems. This paper analyses such a pluralistic system, and is based on an anthropological study involving participant observation and ethnographic interviews. The research focuses on a group of healers-Los Naturistas from urban Bolivia. They are Mestizos and serve the Indian and Indian Mestizo population. The study findings suggest they integrate explanatory models from both the traditional Andean medicine and biomedicine, but are selective in the sicknesses they treat. They predominantly use herbal medicine. As a group of healers Los Naturistas are establishing their specific place in the Bolivian health care system. PMID- 27268215 TI - Humour as Resistance: Deviance and Pathology from a Ludic Perspective. AB - Humour, as one aspect of the ludic, has been argued to evolve with humankind as a higher order of social cognition. In a slum community known for its social dysfunctions and multiple psychopathologies, street humour is used to re-classify messages, situations and relationships, in a variety of contexts. How can we make sense of the discontinuity? This paper builds on work reported in a previous one (Cardena 2003 ). Departing from information collected through participant observation, document analysis and clinical work carried with the community, the first paper documented the ways in which humour aids the assertion of a social identity. In the current paper, this point is developed further to scrutinize the role of 'pathology' under the light of a theory of humour, the ludic and meta communication. The need to address the stature of socially patterned psychopathology as communicative act is emphasized. Deviant and aberrant behaviour, as ludic processes in the culture, embody a higher order of signification that is often overlooked by mental health agents. The failure at addressing this complexity halts the communication between the community's locals and the mental health agents, feeding back the kind of detrimental paradoxes that are at the core of the local's resistance. PMID- 27268216 TI - Review. PMID- 27268217 TI - Postpartum spontaneous coronary, vertebral, and mesenteric artery dissections: a case report. AB - BACKGROUND: Spontaneous coronary artery dissection is a rare cause of myocardial infarction that must always be considered on a clinician's differential diagnosis, particularly in patients <50-years old with a paucity of typical vascular risk factors. CASE PRESENTATION: We describe a case of a 33-year-old white woman, 3 weeks postpartum, presenting with retrosternal chest and back pain, neck pain and stiffness, and intermittent headaches. Subsequent workup revealed concurrent spontaneous dissections in three separate medium-sized arterial beds. CONCLUSIONS: She was successfully managed in a conservative fashion, highlighting that percutaneous or surgical revascularization can often be foregone in favor of conservative medical therapy. PMID- 27268219 TI - Effects of facial attractiveness on personality stimuli in an implicit priming task: an ERP study. AB - OBJECTIVE: Using event-related potentials (ERPs) in a priming paradigm, this study examines implicit priming in the association of personality words with facial attractiveness. METHOD: A total of 16 participants (8 males and 8 females; age range, 19-24 years; mean age, 21.30 years) were asked to judge the color (red and green) of positive or negative personality words after exposure to priming stimuli (attractive and unattractive facial images). The positive personality words primed by attractive faces or the negative personality words primed by unattractive faces were defined as congruent trials, whereas the positive personality words primed by unattractive faces or the negative personality words primed by attractive faces were defined as incongruent trials. RESULTS: Behavioral results showed that compared with the unattractive faces trials, the trials that attractive faces being the priming stimuli had longer reaction times and higher accuracy rates. Moreover, a more negative ERP deflection (N2) component was observed in the ERPs of the incongruent condition than in the ERPs of the congruent condition. In addition, the personality words presented after the attractive faces elicited larger amplitudes from the frontal region to the central region (P2 and P350-550 ms) compared with the personality words after unattractive faces as priming stimuli. CONCLUSION: The study provides evidence for the facial attractiveness stereotype ('What is beautiful is good') through an implicit priming task. PMID- 27268218 TI - A novel point-of-care testing strategy for sexually transmitted infections among pregnant women in high-burden settings: results of a feasibility study in Papua New Guinea. AB - BACKGROUND: Sexually transmitted and genital infections in pregnancy are associated with an increased risk of adverse maternal and neonatal health outcomes. High prevalences of sexually transmitted infections have been identified among antenatal attenders in Papua New Guinea. Papua New Guinea has amongst the highest neonatal mortality rates worldwide, with preterm birth and low birth weight major contributors to neonatal mortality. The overall aim of our study was to determine if a novel point-of-care testing and treatment strategy for the sexually transmitted and genital infections Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Bacterial vaginosis (BV) in pregnancy is feasible in the high-burden, low-income setting of Papua New Guinea. METHODS: Women attending their first antenatal clinic visit were invited to participate. CT/NG and TV were tested using the GeneXpert platform (Cepheid, USA), and BV tested using BVBlue (Gryphus Diagnostics, USA). Participants received same-day test results and antibiotic treatment as indicated. Routine antenatal care including HIV and syphilis screening were provided. RESULTS: Point of-care testing was provided to 125/222 (56 %) of women attending routine antenatal care during the three-month study period. Among the 125 women enrolled, the prevalence of CT was 20.0 %; NG, 11.2 %; TV, 37.6 %; and BV, 17.6 %. Over half (67/125, 53.6 %) of women had one or more of these infections. Most women were asymptomatic (71.6 %; 47/67). Women aged 24 years and under were more likely to have one or more STI compared with older women (odds ratio 2.38; 95 % CI: 1.09, 5.21). Most women with an STI received treatment on the same day (83.6 %; 56/67). HIV prevalence was 1.6 % and active syphilis 4.0 %. CONCLUSION: Point-of care STI testing and treatment using a combination of novel, newly-available assays was feasible during routine antenatal care in this setting. This strategy has not previously been evaluated in any setting and offers the potential to transform STI management in pregnancy and to prevent their associated adverse health outcomes. PMID- 27268220 TI - A preoperative risk-scoring system to predict lymph node metastasis in endometrial cancer and stratify patients for lymphadenectomy. AB - OBJECTIVE: This study aimed to validate the preoperative scoring system adopted in the Kanagawa Cancer Center (KCC) to stratify endometrial cancer patients for lymphadenectomy according to the risk of developing lymph node metastasis (LNM). METHODS: The records of 432 and 221 uterine cancer patients treated in the KCC and Yokohama City University (YCU), respectively, were retrospectively analyzed. The KCC classified patients for LNM risk based on tumor volume, myometrial invasion, histological grade, and serum CA125 levels, while YCU used only myometrial invasion. Lymphadenectomy was omitted for 156 patients with 0 LNM risk, while pelvic lymphadenectomy (PLX) or PLX with para-aortic lymphadenectomy (PLAX) were performed for those with low and high LNM risk, respectively. The predicted and actual LNM rates were compared between the KCC and YCU patients, and cancer recurrence and overall survival were analyzed. RESULTS: There was no difference in survival between patients with LNM score 0 who were or were not treated with lymphadenectomy. None (0%) developed LNM and only 1 (0.6%) had recurrence. Patients who underwent PLX but not PLAX (low LNM score) had a low tumor recurrence rate in the para-aortic nodes (1.3%). The KCC scoring system was significantly more accurate than the YCU system in predicting LNM in the high risk group (P<0.05) and demonstrated that PLAX was unnecessary in almost 50% of the YCU cases. CONCLUSION: The KCC preoperative scoring system is useful to predict LNM risk, and thereby prevent unnecessary lymphadenectomy or to determine its extent in endometrial cancer patients. PMID- 27268221 TI - Selenium Embedded in Metal-Organic Framework Derived Hollow Hierarchical Porous Carbon Spheres for Advanced Lithium-Selenium Batteries. AB - Metal-organic framework derived hollow hierarchical porous carbon spheres (MHPCS) have been fabricated via a facile hydrothermal method combined with a subsequent annealing treatment. Such MHPCS are composed of masses of small hollow carbon bubbles with a size of ~20 nm and shells of ~5 nm thickness interconnected to each other. MHPCS/Se composite is developed as a cathode for Li-Se cells and delivers an initial specific capacity up to 588.2 mA h g(-1) at a current density of 0.5 C, exhibiting an outstanding cycling stability over 500 cycles with a decay rate even down to 0.08% per cycle. This material is capable of retaining up to 200 mA h g(-1) even after 1000 cycles at a current density of 1 C. Such good electrochemical performance may be ascribed to the distinct hollow structure of the carbon spheres and a large amount of Se wrapped within small carbon bubbles, thus not only enhancing the electronic/ionic transport but also providing additional buffer space to adjust volume changes of Se during charge/discharge processes. PMID- 27268222 TI - Comprehensive characterization of the in vitro and in vivo metabolites of ziyuglycoside I in rat microsome, intestinal flora, excretion specimen and fresh tissues based on LC-Q-TOF/MS. AB - Ziyuglycoside I is one of the major active ingredients in Sanguisorba officinalis, a popular medicinal plant in China. In the present study, the metabolites of ziyuglycoside I in rat liver microsome and intestinal flora were identified and structurally characterized, and the metabolic rules were summed based on the LC-Q-TOF/MS system. Then, the metabolites in rat excreta samples were rapidly screened and identified according to the in vitro metabolic rules. Finally, ziyuglycoside I was incubated with fresh liver/lung/kidney/stomach homogenates to further explore the source of the metabolites and reveal the possible metabolic organs involved. Four metabolites in liver microsome were identified as M0-Glu, M0-CH2OH, M0-Glu+CH3, M0-Glu-Ara+CH3. In intestinal flora incubation system, 6 degradation products including M0-Glu-Ara+O, M0-Ara, M0-Glu COOH, M0-Glu, M0-Glu-Ara+O and M0-Ara+H2O were tentatively identified by interpretation of their accurate MS(1) and MS(2) data. Fifteen metabolites in rat urine and feces were identified, and most of the metabolites were attributed to the transformation in liver microsome and intestinal flora. Specifically, more than a dozen of new metabolites were identified in rat fresh tissues, and ziyuglycoside II was confirmed as the major metabolite in rats. PMID- 27268223 TI - Medicinal cannabis: Principal cannabinoids concentration and their stability evaluated by a high performance liquid chromatography coupled to diode array and quadrupole time of flight mass spectrometry method. AB - In the last few years, there has been a boost in the use of cannabis-based extracts for medicinal purposes, although their preparation procedure has not been standardized but rather decided by the individual pharmacists. The present work describes the development of a simple and rapid high performance liquid chromatography method with UV detection (HPLC-UV) for the qualitative and quantitative determination of the principal cannabinoids (CBD-A, CBD, CBN, THC and THC-A) that could be applied to all cannabis-based medicinal extracts (CMEs) and easily performed by a pharmacist. In order to evaluate the identity and purity of the analytes, a high-resolution mass spectrometry (HPLC-ESI-QTOF) analysis was also carried out. Full method validation has been performed in terms of specificity, selectivity, linearity, recovery, dilution integrity and thermal stability. Moreover, the influence of the solvent (ethyl alcohol and olive oil) was evaluated on cannabinoids degradation rate. An alternative extraction method has then been proposed in order to preserve cannabis monoterpene component in final CMEs. PMID- 27268224 TI - Effects of previous ovarian drilling on cumulative ongoing pregnancy rates among patients with polycystic ovarian syndrome undergoing in vitro fertilization. AB - OBJECTIVE: To determine if history of undergoing laparoscopic ovarian drilling (LOD) was associated with changes in cumulative ongoing pregnancy rates following in-vitro fertilization in patients with polycystic ovary syndrome (PCOS). METHODS: The present retrospective study was performed in an in vitro fertilization unit in Xiamen, China, between June 1, 2008 and December 31, 2012. Patient characteristics and in vitro fertilization treatment outcomes were compared between patients with PCOS and a history of LOD (LOD group), patients with PCOS without a history of LOD (no-LOD group), and age-matched patients without PCOS and with no history of LOD (age-matched group). RESULTS: The study included 110 patients in the LOD group, 127 patients in the no-LOD group, and 990 patients in the age-matched group. A lower number of retrieved oocytes, fewer available embryos, and a lower number of cryopreserved embryos were observed in among patients in the LOD-group compared with the other groups (P<=0.001). No differences in birth rates following fresh embryo transfers were observed between the LOD-group, and the age-matched group (P=0.274) and the no-LOD group (P=0.120). A higher adjusted odds ratio of cumulative pregnancy per initiated in vitro fertilization cycle was observed in the no-LOD group when compared with the LOD group (1.976; 95% confidence interval 1.091-3.580). CONCLUSION: LOD could compromise cumulative ongoing pregnancy rates during subsequent in vitro fertilization. PMID- 27268225 TI - Editorial Comment. PMID- 27268226 TI - Findings from a comprehensive diarrhoea prevention and treatment programme in Lusaka, Zambia. AB - BACKGROUND: The Programme for the Awareness and Elimination of Diarrhoea (PAED) was a pilot comprehensive diarrhoea prevention and control programme aimed to reduce post-neonatal, all-cause under-five mortality by 15 % in Lusaka Province. Interventions included introduction of the rotavirus vaccine, improved clinical case management of diarrhoea, and a comprehensive community prevention and advocacy campaign on hand washing with soap, exclusive breastfeeding up to 6 months of age, and the use of ORS and Zinc. This study aimed to assess the impact of PAED on under-5 mortality. METHODS: The study was a pre-post evaluation design. The Demographic and Health Survey style population-based two-stage approach was used to collect data at the beginning of the intervention and 3 years following the start of intervention implementation in Lusaka province. The primary outcome of interest was an all-cause, post-neonatal under-five mortality rate defined as the probability of dying after the 28th day and before the fifth birthday among children aged 1-59 months. The Kaplan-Meier time to event analysis was used to estimate the probability of death; multiplying this probability by 1000 to yield the post-neonatal mortality rate. Survival-time inverse probability weighting model was used to estimate Average Treatment Effect (ATE). RESULTS: The percentage of children under age 5 who had diarrhoea in the last 2 weeks preceding the survey declined from 15.8 % (95 % CI: 15.2 %, 16.4 %) in 2012 to 12.7 % (95 % CI: 12.3 %, 13.2 %) in 2015. Over the same period, mortality in post neonatal children under 5 years of age declined by 34 %, from an estimated rate of 29 deaths per 1000 live births (95 % CI: (26, 32) death per 1000 live births) to 19 deaths per 1000 live births (95 % CI: (16, 21) death per 1000 live births). When every child in the population of children aged 1-59 months is exposed to the intervention, the average time-to-death was estimated to be about 8 months more than when no child is exposed (ATE = 7.9; 95 % CI: 4.4,11.5; P < 0.001). CONCLUSION: Well-packaged diarrhoea preventive and treatment interventions delivered at the clinic and community-level could potentially reduce probability of death among children aged 1-59 months. PMID- 27268228 TI - Fucose decorated solid-lipid nanocarriers mediate efficient delivery of methotrexate in breast cancer therapeutics. AB - The present study is designed to engineer fucose anchored methotrexate loaded solid lipid nanoparticles (SLNs) to target breast cancer. The developed nano carriers were characterized with respect to particle size, PDI, zeta potential, drug loading and entrapment, in-vitro release etc. The characterized formulations were used to comparatively assess cellular uptake, cell-viability, apoptosis, lysosomal membrane permeability, bioavailability, biodistribution, changes in tumor volume and animal survival. The ex-vivo results showed greater cellular uptake and better cytotoxicity at lower IC50 of methotrexate in breast cancer cells. Further, we observed increased programmed cell death (apoptosis) with altered lysosomal membrane permeability and better rate of degradation of lysosomal membrane in-vitro. On the other hand, in-vivo evaluation showed maximum bioavailability and tumor targeting efficiency with minimum secondary drug distribution in various organs with formulated and anchored nano-carrier when compared with free drug. Moreover, sizeable reduction in tumor burden was estimated with fucose decorated SLNs as compared to that seen with free MTX and SLNs-MTX. Fucose decorated SLNs showed promising results to develop therapeutic interventions for breast cancer, and paved a way to explore this promising and novel nano-carrier which enables to address breast cancer. PMID- 27268227 TI - Social and psychological correlates of unprotected anal intercourse among Hispanic-American women: implications for STI/HIV prevention. AB - Heterosexual anal intercourse is associated with increased risk for HIV and other sexually transmitted infections. Research on the social and psychological risk factors associated with heterosexual unprotected anal intercourse among Hispanic women in the USA is limited. We examined demographic, mental health, relationship power, sexual self-efficacy, self-esteem, acculturation and HIV knowledge as correlates of unprotected anal intercourse among 514 HIV-negative Hispanic women, 18 to 59 years of age, residing in one urban county in southern Florida. In both unadjusted and adjusted results, the likelihood of engaging in unprotected anal intercourse was associated with food insecurity in the past 30 days (adjusted odds ratio [AOR] = 1.57, 95% confidence interval [CI] 1.03, 2.40) and more interpersonal power attributed to the male partner (AOR = 1.63, 95%CI 1.08, 2.45). Not significant, yet of possible importance, were ever having engaged in exchange sex (AOR = 1.96, 95%CI = 0.97, 3.98) and lower HIV knowledge (AOR = 0.80, 95%CI = 0.63, 1.01). Interventions aimed at reducing heterosexual unprotected anal intercourse risk for HIV infection among Hispanic women may benefit by addressing socioeconomic and interpersonal issues, and assessing HIV knowledge and comprehension. PMID- 27268229 TI - Detection of reassortant avian influenza A (H11N9) virus in environmental samples from live poultry markets in China. AB - BACKGROUND: Avian influenza viruses have caused human infection and posed the pandemic potential. Live poultry markets are considered as a source of human infection with avian influenza viruses. Avian influenza routine surveillance of live poultry markets is taken annually in China. We isolated the 2 H11N9 influenza virus from the surveillance program. To better understand the risk caused by these new viruses, we characterize the genetic and pathogenicity of the two viruses. METHODS: Viral isolation was conducted with specific pathogen-free (SPF) embryonated chicken eggs. Whole genome was sequenced, and phylogenetic analysis was conducted. RESULTS: Two H11N9 viruses were identified, with all 8 segments belonging to the Eurasian lineage. The HA, NA, M, NS and PA genes were similar to virus isolates from ducks, and the NP, PB2 and PB1 gene segments were most similar to those viruses from wild birds, indicating that the H11N9 viruses might represent reassortant viruses from poultry and wild birds. The HA receptor binding preference was avian-like, and the cleavage site sequence of HA showed low pathogenic. The NA gene showed 94.6 % identity with the novel H7N9 virus that emerged in 2013. There was no drug resistance mutation in the M2 protein. The Asn30Asp and Thr215Ala substitutions in the M1 protein implied a potentially increased pathogenicity in mice. Both viruses were low-pathogenic strains, as assessed by the standards of intravenous pathogenicity index (IVPI) tests. CONCLUSION: Two reassortant H11N9 avian influenza viruses were detected. These viruses showed low pathogenicity to chickens in the IVPI test. Public health concern caused by the reassortant H11N9 viruses should be emphasized during the future surveillance. PMID- 27268231 TI - [Poisoning by illegal drugs in young children in spanish paediatric emergency departments]. PMID- 27268230 TI - Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients. AB - BACKGROUND: Early survival following severe injury has been improved with refined resuscitation strategies. Multiple organ dysfunction syndrome (MODS) is common among this fragile group of patients leading to prolonged hospital stay and late mortality. MODS after trauma is widely attributed to dysregulated inflammation but the precise mechanics of this response and its influence on organ injury are incompletely understood. This study was conducted to investigate the relationship between early lymphocyte responses and the development of MODS during admission. METHODS: During a 24-month period, trauma patients were recruited from an urban major trauma centre to an ongoing, observational cohort study. Admission blood samples were obtained within 2 h of injury and before in-hospital intervention, including blood transfusion. The study population was predominantly male with a blunt mechanism of injury. Lymphocyte subset populations including T helper, cytotoxic T cells, NK cells and gammadelta T cells were identified using flow cytometry. Early cytokine release and lymphocyte count during the first 7 days of admission were also examined. RESULTS: This study demonstrated that trauma patients who developed MODS had an increased population of NK dim cells (MODS vs no MODS: 22 % vs 13 %, p < 0.01) and reduced gammadelta-low T cells (MODS vs no MODS: 0.02 (0.01-0.03) vs 0.09 (0.06-0.12) * 10^9/L, p < 0.01) at admission. Critically injured patients who developed MODS (n = 27) had higher interferon gamma (IFN-gamma) concentrations at admission, compared with patients of matched injury severity and shock (n = 60) who did not develop MODS (MODS vs no MODS: 4.1 (1.8-9.0) vs 1.0 (0.6-1.8) pg/ml, p = 0.01). Lymphopenia was observed within 24 h of injury and was persistent in those who developed MODS. Patients with a lymphocyte count of 0.5 * 10(9)/L or less at 48 h, had a 45 % mortality rate. CONCLUSIONS: This study provides evidence of lymphocyte activation within 2 h of injury, as demonstrated by increased NK dim cells, reduced gammadelta-low T lymphocytes and high blood IFN-gamma concentration. These changes are associated with the development of MODS and lymphopenia. The study reveals new opportunities for investigation to characterise the cellular response to trauma and examine its influence on recovery. PMID- 27268232 TI - Association of established thyroid peroxidase autoantibody (TPOAb) genetic variants with Hashimoto's thyroiditis. AB - Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid diseases (AITD) characterized by progressive destruction of thyroid tissue that may lead to hypothyroidism. High thyroid autoantibodies against thyroid peroxidase (TPOAb) levels are present in 90% of patients with HT and serve as a clinical marker for the detection of early AITD/HT. The main aim of our study was to test whether recently identified genetic variants associated with TPOAb are also involved in HT development. A total of 504 unrelated individuals, including 200 patients with HT and 304 controls, were involved in this study. Diagnosis of HT cases was based on clinical examination, measurement of thyroid hormones (TSH and fT4) and antibodies (TgAb, TPOAb) and ultrasound examination. We selected and genotyped 14 known TPOAb-associated genetic variants. Case-control logistic regression model was used to test the association of selected genetic variants with HT. Additionally, we tested association of the same genetic variants with thyroid related quantitative traits (TPOAb levels, TgAb levels and thyroid gland volume) using linear regression. Three genetic variants showed nominal association with HT; rs10774625 in ATXN2 gene (p = 0.0149, OR = 0.73, CI = 0.56 0.94), rs7171171 near RASGRP1 gene (p = 0.0356, OR = 1.4, CI = 1.02-1.92) and rs11675434 in TPO gene (p = 0.041, OR = 1.31, CI = 1.01-1.69). Two of these SNPs (rs1077462, rs11675434) also showed association with TPOAb levels (p = 0.043, beta = -0.39; p = 0.042, beta = 0.40, respectively) and one (rs7171171) was associated with thyroid gland volume (p = 0.0226, beta = -0.21). Our findings suggest that variants inside or near TPO, ATXN2 and RASGRP1 genes are associated with HT. Identified loci are novel to HT and represent good basis for further exploration of HT susceptibility. PMID- 27268233 TI - Mechanism of Charge Transfer from Plasmonic Nanostructures to Chemically Attached Materials. AB - Plasmonic metal nanoparticles can efficiently convert the energy of visible photons into the energy of hot charge carriers within the nanoparticles. These energetic charge carriers can transfer to molecules or semiconductors, chemically attached to the nanoparticles, where they can induce photochemical transformations. Classical models of photoinduced charge excitation and transfer in metals suggest that the majority of the energetic charge carriers rapidly decay within the metal nanostructure before they are transferred into the neighboring molecule or semiconductor, and therefore, the efficiency of charge transfer is low. Herein, we present experimental evidence that calls into question this conventional picture. We demonstrate a system where the presence of a molecule, adsorbed on the surface of a plasmonic nanoparticle, significantly changes the flow of charge within the excited plasmonic system. The nanoparticle adsorbate system experiences high rates of direct, resonant flow of charge from the nanoparticle to the molecule, bypassing the conventional charge excitation and thermalization process taking place in the nanoparticle. This picture of charge transfer suggests that the yield of extracted hot electrons (or holes) from plasmonic nanoparticles can be significantly higher than the yields expected based on conventional models. We discuss a conceptual physical framework that allows us to explain our experimental observations. This analysis points us in a direction toward molecular control of the charge transfer process using interface and local field engineering strategies. PMID- 27268234 TI - Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast. AB - Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5' promoter and 3' termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast. PMID- 27268235 TI - Absence of residual structure in the intrinsically disordered regulatory protein CP12 in its reduced state. AB - The redox switch protein CP12 is a key player of the regulation of the Benson Calvin cycle. Its oxidation state is controlled by the formation/dissociation of two intramolecular disulphide bridges during the day/night cycle. CP12 was known to be globally intrinsically disordered on a large scale in its reduced state, while being partly ordered in the oxidised state. By combining Nuclear Magnetic Resonance and Small Angle X-ray Scattering experiments, we showed that, contrary to secondary structure or disorder predictions, reduced CP12 is fully disordered, with no transient or local residual structure likely to be precursor of the structures identified in the oxidised active state and/or in the bound state with GAPDH or PRK. These results highlight the diversity of the mechanisms of regulation of conditionally disordered redox switches, and question the stability of oxidised CP12 scaffold. PMID- 27268236 TI - Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 ameliorates obesity related insulin resistance. AB - Excess 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) may be implicated in the development of obesity related metabolic disorders. The present study measured the expression level of 11beta-HSD1 in visceral adipose tissues from 23 patients undergoing abdominal operation. Correlation of 11beta-HSD1 expression with BMI, waist-to-hip ratio (WHR), HOMA-IR, and serum lipids was evaluated by spearman correlation analysis. High-fat diet-induced obese (DIO) rats were orally dosed with BVT.2733 for 4 weeks. Weight, plasma insulin, and lipids were detected at the end of the treatment. The effects of 11beta-HSD1 inhibition on the key insulin-signaling cascade and adipocytokines were measured by western blot and ELISA respectively. 11beta-HSD1 was increased in patients with central obesity, the expression level of which was closely related with WHR (r = 0.5851), BMI (r = 0.4952), and HOMA-IR (r = 0.4637). Obesity related insulin resistance in high-fat DIO rats, as reflected by a marked decrease in IRS-1, IRS-2, GLUT4, and PI3K, could be attenuated by 11beta-HSD1 inhibition. Furthermore, the down-regulation of 11beta-HSD1 could correct the disordered profiles of adipocytokines including adiponectin, IL-6, and TNF-alpha. These findings indicated that 11beta-HSD1 inhibition can give a potential benefit in reducing obesity and lowering insulin resistance by modulating the insulin-signaling pathway and adipocytokine production. PMID- 27268237 TI - Disparities in the experience and treatment of dental caries among children aged 9-18 years: the cross-sectional study of Korean National Health and Nutrition Examination Survey (2012-2013). AB - BACKGROUND: The aim of this study is to examine the association between parental socioeconomic status (SES) and the experience as well as treatment of dental caries among children aged 9 to 18 years. METHODS: Data from 1253 children aged 9 18 years from the Korean National Health and Nutrition Examination Survey (2012 2013) were analyzed. Parental socioeconomic status was measured using household income level and maternal educational level. The decayed, missing, and filled teeth (DMFT) index was used to measure experience of dental caries (DMFT >= 1). Non-treatment of dental caries was measured according to whether the participants who experienced dental caries used a dental service at a dental clinic to treat caries during the previous year. Logistic regression was used to investigate the association between parental socioeconomic status and the experience of dental caries as well as the association between parental socioeconomic status and the non-treatment of dental caries among children that have experienced caries. RESULTS: A total of 808 subjects (64.5 %) experienced dental caries among 1253 participants, and 582 of these 808 subjects (72.0 %) did not receive treatment among those having experience of dental caries. Parental socioeconomic status was not associated with experience of dental caries. However, those from low- and middle-income households were less likely to receive treatment than those from high-income households (odds ratio [OR] 2.11 [95 % confidence interval (CI) 1.16 3.86], OR 2.14 [95 % CI 1.27-3.62]). In particular, those from low- and middle income households who had regular dental checkups were more likely to have untreated caries than those from high-income households (OR 3.58 [95 % CI 1.25 10.24]). CONCLUSIONS: This study demonstrates the parental household income related disparities in children's dental health treatment. Efforts should be made to lower financial barriers to dental health services, particularly among those from low-income households, in order to reduce dental health disparities in the treatment of caries in children. PMID- 27268239 TI - Does Age Influence the Risk of Incident Knee Osteoarthritis After a Traumatic Anterior Cruciate Ligament Injury? AB - BACKGROUND: The development of radiographic knee osteoarthritis (OA) after an anterior cruciate ligament (ACL) rupture has long been studied and proven in the adolescent population. However, similar exhaustive investigations have not been conducted in mature-aged athletes or in older populations. PURPOSE: To identify whether an older adult population had an increased risk of incident radiographic knee OA after a traumatic knee injury compared with a young adult population. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients with ACL ruptures who underwent primary reconstruction were enrolled in a prospective, longitudinal single-center study over 15 years. The adult cohort was defined as participants aged >=35 years who had a knee injury resulting in an ACL tear, the adolescent-young cohort suffered similar knee injuries and were aged <=25 years, and a third cohort of participants aged 26 to 34 years who suffered a knee injury was included to identify the existence of any age-related dose-response relationship for the onset of radiographic knee OA. A Kaplan-Meier survival analysis was employed to determine the occurrence of incident radiographic OA across the study populations at 2, 5, 10, and 15 years after reconstruction. Significance at each time point was analyzed using chi-square tests. RESULTS: A total of 215 patients, including 112 adolescents (mean age, 20.4 years; 50.9% female), 71 patients aged 26 to 34 years (mean age, 29.2 years; 42.3% female), and 32 adults (mean age, 40.2 years; 59.4% female), were assessed for International Knee Documentation Committee (IKDC) grading on knee radiographs. It was found that 53.0% and 77.8% of adults at a respective 10 and 15 years after reconstruction had an IKDC grade of B or greater compared with 17.7% and 61.6% of the adolescent-young cohort. Chi-square testing found that adults developed OA earlier than adolescents at 5 and 10 years after reconstruction (P = .017 and P < .0001, respectively). However, survival analysis did not demonstrate that adults were more likely to develop radiographic knee OA at 15 years after reconstruction compared with the adolescent-young cohort (P = .4). CONCLUSION: The age at which an ACL injury is sustained does not appear to influence the rate of incident radiographic knee OA, although mature-aged athletes are likely to arrive at the OA endpoint sooner. PMID- 27268238 TI - Left ventricular long axis strain: a new prognosticator in non-ischemic dilated cardiomyopathy? AB - BACKGROUND: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. METHODS AND RESULTS: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF <=45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > -5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p < 0.05), presence of LGE (HR: 2.51, p < 0.05) and LAS (HR: 1.28, p < 0.05) were independent predictors for cardiac events. In a sequential cox regression analysis LAS offered significant incremental information (p < 0.05) for the prediction of outcome in addition to LGE and LVEDV/BSA. Using a dichotomous three point scoring model for risk stratification, including LVEF <35 %, LAS > -10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. CONCLUSION: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters. PMID- 27268240 TI - Efficacy of a Subacromial Corticosteroid Injection for Persistent Pain After Arthroscopic Rotator Cuff Repair. AB - BACKGROUND: Corticosteroid injections have been widely used for reducing shoulder pain. However, catastrophic complications induced by corticosteroid such as infections and tendon degeneration have made surgeons hesitant to use a corticosteroid injection as a pain control modality, especially during the postoperative recovery phase. PURPOSE: To determine the effectiveness and safety of a subacromial corticosteroid injection for persistent pain control during the recovery period and to analyze the factors causing persistent pain after arthroscopic rotator cuff repair. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 458 patients who underwent arthroscopic rotator cuff repair were included in this study. Patient-specific parameters, tear size and pattern, and pain intensity were reviewed. Seventy-two patients were administered a postoperative subacromial corticosteroid injection under ultrasound guidance. The corticosteroid injection was administered to patients who awakened overnight because of constant severe shoulder pain or whose pain was exacerbated at the time of rehabilitation exercises within 8 weeks after surgery. Pain intensity, patient satisfaction, and functional outcomes using the American Shoulder and Elbow Surgeons (ASES) and Constant scores were compared between the patients with and without a subacromial corticosteroid injection. The retear rate was evaluated with magnetic resonance imaging at 6 months postoperatively. RESULTS: In patients with an injection, the mean (+/-SD) visual analog scale for pain (pVAS) score was 7.7 +/- 1.2 at the time of the injection. This significantly decreased to 2.3 +/- 1.4 at the end of the first month after the injection, demonstrating a 70.2% reduction in pain (P < .01). At 3 months after the injection, the mean pVAS score was 1.2 +/- 1.8. Functional outcomes at final follow-up showed no significant differences between patients with and without an injection (ASES score: 90.1 +/- 14.6 with injection, 91.9 +/- 8.2 without injection [P = .91]; Constant score: 89.1 +/- 12.9 with injection, 84.5 +/- 13.0 without injection [P = .17]). Patients with an injection showed no significant increase in the retear rate (6.8% with injection, 18.4% without injection; P = .06). According to the tear pattern, L-shaped rotator cuff tears (41.8%) showed a higher occurrence of severe postoperative persistent pain. Preoperative shoulder stiffness was revealed as a predisposing factor for persistent pain (odds ratio, 0.2; P = .04). CONCLUSION: A subacromial corticosteroid injection can be considered as a useful and safe modality for the treatment of patients having severe persistent pain during the recovery phase after arthroscopic rotator cuff repair. PMID- 27268241 TI - [Can we consider the journalist an actor in suicide prevention?] AB - INTRODUCTION: After more than 50 years of dedicated research, media coverage of suicide is now well known to have a significant influence on the suicide epidemiology. This influence is supposed to result from two opposite effects. The Werther effect (WE) refers to the robust increase of suicide rates following the publication of a suicide story. This specific kind of mass cluster implies a suggestion process, i.e. imitation of the depicted death by vulnerable persons. In contract, the preventive potential of medias has been labeled the "Papageno effect" (PE). Although more recently discovered and far less known, PE predicts that journalists can help prevent suicidal behaviors beyond a simple WE reduction. Because PE and WE directly bridge journalistic productions to suicidal events, several national and international health organisms (including the World Health Organization) started to see the media as new prevention opportunities. In this paper, we intend to assess the extent to which journalists can be considered as public health actors in the specific field of suicide prevention. METHODS: Based on a critical review of the so-called Media effect studies, we explore the opportunities, limits and constraints of collaborating with media professionals for public health actions. For that purpose, we focus on the main strategy employed so far, namely providing recommendations for more cautious coverage of suicide. An overview of the efficacy of these recommendations serves not only as a starting point for understanding how public health and journalistic perspectives can confront, but also how they can be combined in a fertile way. RESULTS: Numerous suicide prevention organisms developed strategies in order to assist journalists in reporting suicide stories in a safer way. As a formal support to these strategies, around 30 national or international guides have been produced around the word, with the shared aim of reducing WE and, eventually, promoting PE. The recommendations about articles' style and content that compose these guides were shown to be similar across the countries. They mostly meet public health concerns, rest on the available knowledge about the two effects' determinants and thus advocate for a less quantitatively and qualitatively prominent coverage. However, the way the guides were produced and implemented shows considerable variations. While most countries solely edited and/or distributed the recommendations with no complementary measures, several organisms associated their publication with promotion actions towards the journalists and general public. Evidence for the impact of the guides' publication on suicide rates, although encouraging, are seriously limited by methodological considerations. As a consequence, their efficacy is more often assessed in terms of media compliance to the recommendations. The extent to which media items respect the guidelines depends considerably on the way journalists are invited - or not - to resort to them. While the strategy seems inefficient when limited to a simple publication, the quality of suicide portrayal significantly improves when the guides are part of a whole prevention campaign dealing with suicide coverage. Moreover the journalist's implication at each step of the process seems a crucial point for its success. DISCUSSION: Media professionals are submitted to their own codes, constraints and missions which do not necessarily fit with public health concerns. If considered as prescriptions to reduce the suicide rates, journalists might see recommendations for a more cautious coverage to be a threat to their independence, thus accounting for their non-compliance. On the other hand, a real collaborative approach based on shared skills and knowledge could help sensitize journalists to a responsibility that PE and WE inevitably give them. Under these conditions, recommendations can become a precious resource to help media professional when facing a sensitive issue and finally contribute to fight against suicide. PMID- 27268242 TI - Transcriptome analysis of Ophiocordyceps sinensis before and after infection of Thitarodes larvae. AB - Ophiocordyceps sinensis, also referred to as the Chinese caterpillar fungus, is a rare entomopathogenic fungus found in the Qinghai-Tibetan Plateau that is used as a traditional Chinese medicine. O. sinensis parasitizes the larvae of the ghost moth Thitarodes. Characterization of the transcriptome of O. sinensis before and after host infection may provide novel insight into the process by which the fungus interacts with Thitarodes and may help researchers understand how to sustain this valuable resource. In this study, we performed RNA-sequencing (RNA seq) using Illumina HiSeqTM 2000 technology to generate gene expression profiles of two developmental stages of O. sinensis. Thread-like hyphae before infection and yeast-like hyphal bodies after infection of host larvae were collected for transcriptome analysis. We found that 1640 genes were differentially expressed (q value < 0.05), of which 818 were upregulated (49.878 %) and 822 were downregulated (50.122 %). Gene ontology (GO) analysis revealed that the differentially expressed genes (DEGs) were especially enriched in terms associated with Biological Process and Molecular Function. Several genes encoding transporter and permease proteins, three glycoside hydrolases, two mycotoxin related proteins, an antigen protein, and an allergen were identified as being significantly up- or downregulated. Collectively, our findings provide a novel resource for understanding O. sinensis during two critical developmental stages, and offer the opportunity to further investigate the functional mechanisms underlying these stage-specific molecular differences. PMID- 27268243 TI - Endophytic Cryphonectriaceae on native Myrtales: Possible origin of Chrysoporthe canker on plantation-grown Eucalyptus. AB - Chrysoporthe austroafricana (Cryphonectriaceae) is a damaging canker pathogen on Eucalyptus species in Southern Africa. Recent studies have shown that the fungus occurs on native Syzygium species and that it has apparently undergone a host range expansion from these native trees to infect non-native Eucalyptus. The aim of this study was to consider whether Chr. austroafricana and other Cryphonectriaceae might exist as endophytes in native Myrtaceae, providing a source of inoculum to infect non-native Myrtales. Healthy branches were collected from Myrtaceae in Mozambique, incubated in florist foam, allowed to dry gradually and monitored for the appearance of fruiting bodies resembling species in the Cryphonectriaceae. Isolates were identified based on DNA sequence data. Two species in the Cryphonectriaceae were obtained, representing the first evidence that species in the Cryphonectriaceae occur as endophytes on native Myrtales, thus providing a source of inoculum to infect non-native and susceptible trees. This has important implications regarding the movement of planting stock used by ornamental tree and forestry enterprises. PMID- 27268244 TI - Evolutionary relationships within the Phytophthora cactorum species complex in Europe. AB - The Phytophthora cactorum species complex in Europe is composed of P. cactorum, Phytophthora hedraiandra, and a hybrid species Phytophthora * serendipita. Evolutionary analyses using the amplified fragment length polymorphism (AFLP) method were carried out on 133 isolates from 19 countries. The AFLP data were complemented by sequence analysis of three genes (ITS region of ribosomal RNA gene, phenolic acid decarboxylase - Pheca I, and Cytochrome oxidase - Cox I), morphometric analysis and cardinal temperature data. The high proportion of clonal genotypes, low gene flow among groups, which was defined by the structure analysis, and low Nei's gene diversity confirms the homothallic life cycle of the groups. On the other hand, the ITS, Cox I and Pheca I sequence data support occasional hybridization between species. The structure K = 5 grouping revealed two groups of hybrid origin (C2 and F). While the C2 group resembles P. * serendipita, the F group includes Finnish isolates characterized by high oogonial abortion rates and slow growth. The morphological characters routinely used in identification of Phytophthora species are not useful for delimitation of species from the P. cactorum complex. Therefore, we discuss the status of P. hedraiandra as a separate species. The epitypification of P. cactorum is proposed. PMID- 27268245 TI - Carbohydrate changes during growth and fruiting in Pleurotus ostreatus. AB - The carbohydrate distribution in mushrooms is reported changing greatly in its different regions during growth and fruiting. In this study, the carbohydrate distribution in the compost and fruiting bodies of Pleurotus ostreatus was analysed. Sugar, polyol, polysaccharide, and chitin content during different growth phases and in different regions of the mushroom were determined. Results indicate that trehalose, mannitol, and glucose were first accumulated in the compost and then decreased during differentiation and growth of fruiting bodies. Meanwhile, trehalose, mannitol, and glucose also accumulated in the fruiting bodies and primarily distributed in the stipe, base, and pileus region, respectively. Polysaccharides mainly accumulated within the pileus and stipe regions, and chitin was mainly observed in the base region. These findings provide insights into carbohydrate function and utilisation during mushroom growth. PMID- 27268246 TI - Influence of plant genotype on the cultivable fungi associated to tomato rhizosphere and roots in different soils. AB - Rhizosphere and root-associated microbiota are crucial in determining plant health and in increasing productivity of agricultural crops. To date, research has mainly focused on the bacterial dimension of the microbiota. However, interest in the mycobiota is increasing, since fungi play a key role in soil ecosystems. We examined the effect of plant genotype, soil, and of Fusarium oxysporum f. sp. lycopersici (Fol) on the cultivable component of rhizosphere and root-associated mycobiota of tomato. Resistant and susceptible varieties were cultivated on two different soils (A and B), under glasshouse conditions. Isolated fungi were identified by morphological and molecular approaches. Differences were found between the rhizosphere and the roots, which in general displayed a lower number of species. The structure of the mycobiota was significantly affected by the soil type in the rhizosphere as well as by the plant genotype within the roots (NPERMANOVA, p < 0.05). The addition of Fol changed the community structure, particularly in soil A, where Penicillium spp. and Fusarium spp. were the dominant responding fungi. Overall, the results indicated that i) soil type and plant genotype affect the fungal communities; ii) plant roots select few species from the rhizosphere; and iii) the fungal community structure is influenced by Fol. PMID- 27268247 TI - Camptothecine production by mixed fermentation of two endophytic fungi from Nothapodytes nimmoniana. AB - Two endophytic fungi isolated from the endangered plant Nothapodytes nimmoniana (Grah.) Mabb. were found to effectively synthesize CPT independent of their host plant under submerged fermentation conditions. Molecular characterization of fungi revealed their identity as Colletotrichum fructicola SUK1 (F1) and Corynespora cassiicola SUK2 (F2). Mixed fermentation experiments were carried out to study the effect of microbial signalling between the two fungal species on camptothecine production. Effect of culture parameters on CPT production was studied for both mono-cultures (F1 and F2) separately as well as for the mixed fermentation (F1 + F2). Further the most influencing ones were optimized statistically using response surface methodology. Statistical model based optimized parameters were whey (70 %), agitation rate (110 rpm), temperature (30 degrees C), and incubation period (7 d) for the mixed fermentation. Monocultures of the two fungal species F1 and F2 yielded CPT up to 33 +/- 1.1 mg l(-1)and 69 +/- 1.1 mg l(-1), respectively; while their mixed fermentation under the optimized conditions yielded up to 146 +/- 0.2 mg l(-1). HPLC and LC-MS/MS techniques were used to analyze the products obtained. PMID- 27268249 TI - Specific Neuron Placement on Gold and Silicon Nitride-Patterned Substrates through a Two-Step Functionalization Method. AB - The control of neuron-substrate adhesion has been always a challenge for fabricating neuron-based cell chips and in particular for multielectrode array (MEA) devices, which warrants the investigation of the electrophysiological activity of neuronal networks. The recent introduction of high-density chips based on the complementary metal oxide semiconductor (CMOS) technology, integrating thousands of electrodes, improved the possibility to sense large networks and raised the challenge to develop newly adapted functionalization techniques to further increase neuron electrode localization to avoid the positioning of cells out of the recording area. Here, we present a simple and straightforward chemical functionalization method that leads to the precise and exclusive positioning of the neural cell bodies onto modified electrodes and inhibits, at the same time, cellular adhesion in the surrounding insulator areas. Different from other approaches, this technique does not require any adhesion molecule as well as complex patterning technique such as MU-contact printing. The functionalization was first optimized on gold (Au) and silicon nitride (Si3N4) patterned surfaces. The procedure consisted of the introduction of a passivating layer of hydrophobic silane molecules (propyltriethoxysilane [PTES]) followed by a treatment of the Au surface using 11-amino-1-undecanethiol hydrochloride (AT). On model substrates, well-ordered neural networks and an optimal coupling between a single neuron and single micrometric functionalized Au surface were achieved. In addition, we presented the preliminary results of this functionalization method directly applied on a CMOS-MEA: the electrical spontaneous spiking and bursting activities of the network recorded for up to 4 weeks demonstrate an excellent and stable neural adhesion and functional behavior comparable with what expected using a standard adhesion factor, such as polylysine or laminin, thus demonstrating that this procedure can be considered a good starting point to develop alternatives to the traditional chip coatings to provide selective and specific neuron-substrate adhesion. PMID- 27268248 TI - Fusarium proliferatum strains change fumonisin biosynthesis and accumulation when exposed to host plant extracts. AB - Fumonisin concentrations in mycelia and media were studied in liquid Fusarium proliferatum cultures supplemented with host plant extracts. Furthermore, the kinetics of fumonisin accumulation in media and mycelia collected before and after extract addition was analysed as well as the changes in the expression of the FUM1 gene. Fumonisin content in culture media increased in almost all F. proliferatum strains shortly after plant extracts were added. The asparagus extract induced the highest FB level increase and the garlic extract was the second most effective inducer. Fumonisin level decreased constantly until 14th day of culturing, though for some strains also at day 8th an elevated FB level was observed. Pineapple extract induced the highest increase of fum1 transcript levels as well as fumonisin synthesis in many strains, and the peas extract inhibited fungal growth and fumonisin biosynthesis. Moreover, fumonisins were accumulated in mycelia of studied strains and in the respective media. PMID- 27268250 TI - Two new dammarane-type triterpenoid saponins from notoginseng medicinal fungal substance. AB - Two new dammarane-type triterpenoid saponins, namely ginsenoside Rk6 (1) and ginsenoside-Rh22 (2), were isolated from notoginseng medicinal fungal substance. The structures of 1 and 2 were established as 3beta,6alpha,12beta,26 tetrahydroxydammar-20(21),24(25)(E)-diene-6-O-beta-D-glucopyranoside and 3beta,6alpha, 20(S)-trihydroxy-12(R),23(R)-expoxy-13(S),17(S)-dammar-24-ene-6-O beta-D-glucopyranoside on the basis of spectroscopic analysis and chemical analysis, respectively. PMID- 27268251 TI - Functions of Polyamines in Mammals. AB - The content of spermidine and spermine in mammalian cells has important roles in protein and nucleic acid synthesis and structure, protection from oxidative damage, activity of ion channels, cell proliferation, differentiation, and apoptosis. Spermidine is essential for viability and acts as the precursor of hypusine, a post-translational addition to eIF5A allowing the translation of mRNAs encoding proteins containing polyproline tracts. Studies with Gy mice and human patients with the very rare X-linked genetic condition Snyder-Robinson syndrome that both lack spermine synthase show clearly that the correct spermine:spermidine ratio is critical for normal growth and development. PMID- 27268252 TI - Polyamines in Eukaryotes, Bacteria, and Archaea. AB - Polyamines are primordial polycations found in most cells and perform different functions in different organisms. Although polyamines are mainly known for their essential roles in cell growth and proliferation, their functions range from a critical role in cellular translation in eukaryotes and archaea, to bacterial biofilm formation and specialized roles in natural product biosynthesis. At first glance, the diversity of polyamine structures in different organisms appears chaotic; however, biosynthetic flexibility and evolutionary and ecological processes largely explain this heterogeneity. In this review, I discuss the biosynthetic, evolutionary, and physiological processes that constrain or expand polyamine structural and functional diversity. PMID- 27268254 TI - Nonrespiratory mortality and cancer incidence in a cohort of Canadian nickel workers. AB - Mortality and cancer incidence were examined for an updated cohort of nonsinter nickel workers in Sudbury and Port Colborne, Ontario, Canada. Abstract results are provided for those with >= 15 years since first exposure. For circulatory disease mortality, significant elevations were observed overall in many Sudbury work areas and in Port Colborne staff. Underground miners, with first exposure before 1960, displayed significant elevations for pneumoconiosis, as well as silicosis and anthrasilicosis, likely due to crystalline silica. Significant elevations in colorectal cancer incidence were observed in Sudbury underground mining, mining maintenance, and maintenance work areas. Given a case-control study is not practical, the next cohort update should include more detailed occupational exposure assessment, including dust exposure, diesel engine emissions, solvents, various metals, silica, and sulphur dioxide. PMID- 27268253 TI - Aryl Hydrocarbon Receptor-interacting Protein-like 1 Is an Obligate Chaperone of Phosphodiesterase 6 and Is Assisted by the gamma-Subunit of Its Client. AB - Phosphodiesterase 6 (PDE6) is the effector enzyme in the phototransduction cascade and is critical for the health of both rod and cone photoreceptors. Its dysfunction, caused by mutations in either the enzyme itself or AIPL1 (aryl hydrocarbon receptor-interacting protein-like 1), leads to retinal diseases culminating in blindness. Progress in research on PDE6 and AIPL1 has been severely hampered by failure to express functional PDE6 in a heterologous expression system. Here, we demonstrated that AIPL1 is an obligate chaperone of PDE6 and that it enables low yield functional folding of cone PDE6C in cultured cells. We further show that the AIPL1-mediated production of folded PDE6C is markedly elevated in the presence of the inhibitory Pgamma-subunit of PDE6. As illustrated in this study, a simple and sensitive system in which AIPL1 and Pgamma are co-expressed with PDE6 represents an effective tool for probing structure-function relationships of AIPL1 and reliably establishing the pathogenicity of its variants. PMID- 27268255 TI - Introduction to Protein Ensembles and Allostery. PMID- 27268257 TI - Effect of Ion Rigidity on Physical Properties of Ionic Liquids Studied by Molecular Dynamics Simulation. AB - In this work, we have performed molecular dynamics (MD) simulations to compare the structural and dynamical properties of three ionic liquids (ILs), 1-ethyl-3 methyl-imidazolium tetrafluorborate ([EMI(+)][BF4(-)]), 1,1'-dimethyl-4,4' bipyridinium bis(tetrafluorborate) ([VIO(2+)][BF4(-)]2), and 1,1'-dimethyl-4,4' bipyridinium bis(trifluoromethylsulfonyl)imide (bistriflimide in short) ([VIO(2+)][Tf2N(-)]2), aiming to discover the influence of ion rigidity on the physical properties of ILs. [VIO(2+)] is more rigid than [EMI(+)], and [BF4(-)] is more rigid than [Tf2N(-)]. [VIO(2+)][BF4(-)]2 has an anion distribution different from the other two by the higher and sharper peaks in the cation-anion radial distribution functions, reflecting a close-packed local structure of anions around cations. [VIO(2+)][BF4(-)]2 and [VIO(2+)][Tf2N(-)]2 have similar dynamics much slower than [EMI(+)][BF4(-)], and [VIO(2+)][Tf2N(-)]2 shows a more isotropic molecular distribution than [VIO(2+)][BF4(-)]2 and [EMI(+)][BF4(-)]. Additionally, we have simulated two modified viologen-based ILs to reinforce our interpretations. We conclude from the above simulation results that the rigidity of anions influences the alignment of cations and that the rigidity of cations shows a large obstacle to their rotational capacity. Moreover, we have observed a slower diffusion of [VIO(2+)][BF4(-)]2 due to the electrostatic correlations, which stabilizes the ion-cage effect. PMID- 27268256 TI - Chromosomal rearrangement-A rare cause of complement factor I associated atypical haemolytic uraemic syndrome. AB - Chromosomal rearrangements affecting the genes encoding complement factor H and the factor H related proteins have been described in aHUS patients. To date such disorders have not been described in other aHUS associated genes. We describe here a heterozygous 875,324bp deletion encompassing the gene (CFI) encoding complement factor I and ten other genes. The index case presented with aHUS and did not recover renal function. No abnormalities were detected on Sanger sequencing of CFI but a low factor I level led to a multiplex ligation-dependent probe amplification assay being undertaken. This showed a complete heterozygous deletion of CFI. The extent of the deletion and the breakpoint was defined. In the Newcastle aHUS cohort we have identified and report here 32 different CFI variants in 56 patients but to date this is the only deletion that we have identified. This finding although rare does suggest that screening for chromosomal rearrangements affecting CFI should be undertaken in all aHUS patients particularly if the factor I level is unexplainably low. PMID- 27268258 TI - Magnetic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol micelles for docetaxel delivery in breast cancer: an in vitro study on two cell lines of breast cancer. AB - The aim of the present study was to load docetaxel (DCT) and Fe3O4 magnetic nanoparticles (MNPs) in polymeric micelles to concentrate them by an external magnetic field in target tissues. Oleic acid (OA) coated MNPs were prepared by hydrothermal method. The micelles were characterized for their zeta potential, particle size, drug loading and release efficacy. Fe loading efficacy was determined by atomic absorption. The magnetic micelles were characterized by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), transmission electron microscopy and vibrating sample magnetometer (VSM). The cytotoxicity of the micelles was studied by MTT assay on L929 fibroblast cells and also on two breast cancer cell lines of MCF-7 and MDA-MB-231. The optimum formulation showed 70% drug loading efficiency, zeta potential of -2.58 mV, particle size of 144.3 nm and drug release efficiency within 24 h of 68.9% at pH 5.5. Fe was loaded in these nanomicelles 290 MUg/100 ml. TGA results confirmed the coating of MNPs with OA and polymeric micelles. The VSM analysis confirmed superparamagnetic property of the micelles. DCT loaded in micelles showed significantly more cytotoxicity compared to free drug on MCF-7 and MDA-MB-231 cells, but blank magnetic micelles had no significant cytotoxicity on normal fibroblast cells. PMID- 27268259 TI - Synchronization of fractional-order complex-valued neural networks with time delay. AB - This paper deals with the problem of synchronization of fractional-order complex valued neural networks with time delays. By means of linear delay feedback control and a fractional-order inequality, sufficient conditions are obtained to guarantee the synchronization of the drive-response systems. Numerical simulations are provided to show the effectiveness of the obtained results. PMID- 27268260 TI - Real-time object tracking based on scale-invariant features employing bio inspired hardware. AB - We developed a vision sensor system that performs a scale-invariant feature transform (SIFT) in real time. To apply the SIFT algorithm efficiently, we focus on a two-fold process performed by the visual system: whole-image parallel filtering and frequency-band parallel processing. The vision sensor system comprises an active pixel sensor, a metal-oxide semiconductor (MOS)-based resistive network, a field-programmable gate array (FPGA), and a digital computer. We employed the MOS-based resistive network for instantaneous spatial filtering and a configurable filter size. The FPGA is used to pipeline process the frequency-band signals. The proposed system was evaluated by tracking the feature points detected on an object in a video. PMID- 27268261 TI - Health nurses' experiences and attitudes regarding collaboration with dental personnel. AB - BACKGROUND: Collaboration between primary care personnel and dental personnel to prevent early childhood caries has been established in several countries. The purpose of this study was, firstly, to describe health nurses' experiences and attitudes regarding collaboration with dental personnel, and secondly, to identify characteristic of health nurses and health centres associated with the collaboration. METHODS: Health nurses working with children answered a questionnaire. In total, 163 of 296 health nurses (55 %) reported demographic information, referral routines, frequency of and reasons for referral of young children to dental personnel, contact with dental personnel and satisfaction with the collaboration. Data were analysed using multivariate logistic regression. RESULTS: The majority of health nurses (83 %) were familiar with referral routines and 31 % reported referring children to dental personnel monthly or more often. The most frequent reasons for referral were clinical caries (52 %), dental discolouration (38 %) and dental trauma (34 %). Few health nurses (18 %) had contact with dental personnel monthly or more often. Two-thirds of health nurses (71 %) reported being satisfied with the collaboration with dental personnel. Results of multivariate analysis showed that health nurses were more likely to refer children when the proportion of immigrant children under care in the health centres was high than when proportion of immigrant children was low (OR 6.4, CI 2.7-14.9). Health nurses working in small health centres were more likely to be satisfied with the collaboration than health nurses working in large health centres (OR 3.2, CI 1.4-7.0). Health nurses 45 years or older were more likely to possess knowledge of referral routines than younger health nurses (OR 2.7, CI 1.1 6.4). CONCLUSIONS: The results indicated that the majority of health nurses possessed knowledge of collaboration routines and were satisfied with the collaboration. The proportion of immigrant children under care in the health centres, the size of the health centres and the age of health nurses were factors influencing the collaboration between primary care personnel and dental personnel. PMID- 27268262 TI - Plutonium(IV) and (V) Sorption to Goethite at Sub-Femtomolar to Micromolar Concentrations: Redox Transformations and Surface Precipitation. AB - Pu(IV) and Pu(V) sorption to goethite was investigated over a concentration range of 10(-15)-10(-5) M at pH 8. Experiments with initial Pu concentrations of 10( 15) - 10(-8) M produced linear Pu sorption isotherms, demonstrating that Pu sorption to goethite is not concentration-dependent across this concentration range. Equivalent Pu(IV) and Pu(V) sorption Kd values obtained at 1 and 2-week sampling time points indicated that Pu(V) is rapidly reduced to Pu(IV) on the goethite surface. Further, it suggested that Pu surface redox transformations are sufficiently rapid to achieve an equilibrium state within 1 week, regardless of the initial Pu oxidation state. At initial concentrations >10(-8) M, both Pu oxidation states exhibited deviations from linear sorption behavior and less Pu was adsorbed than at lower concentrations. NanoSIMS and HRTEM analysis of samples with initial Pu concentrations of 10(-8) - 10(-6) M indicated that Pu surface and/or bulk precipitation was likely responsible for this deviation. In 10(-6) M Pu(IV) and Pu(V) samples, HRTEM analysis showed the formation of a body centered cubic (bcc) Pu4O7 structure on the goethite surface, confirming that reduction of Pu(V) had occurred on the mineral surface and that epitaxial distortion previously observed for Pu(IV) sorption occurs with Pu(V) as well. PMID- 27268263 TI - Comprehensive characterization of programmed death ligand structural rearrangements in B-cell non-Hodgkin lymphomas. AB - Programmed death ligands (PDLs) are immune-regulatory molecules that are frequently affected by chromosomal alterations in B-cell lymphomas. Although PDL copy-number variations are well characterized, a detailed and comprehensive analysis of structural rearrangements (SRs) and associated phenotypic consequences is largely lacking. Here, we used oligonucleotide capture sequencing of 67 formalin-fixed paraffin-embedded tissues derived from primary B-cell lymphomas and 1 cell line to detect and characterize, at base-pair resolution, SRs of the PDL locus (9p24.1; harboring PDL1/CD274 and PDL2/PDCD1LG2). We describe 36 novel PDL SRs, including 17 intrachromosomal events (inversions, duplications, deletions) and 19 translocations involving BZRAP-AS1, CD44, GET4, IL4R, KIAA0226L, MID1, RCC1, PTPN1 and segments of the immunoglobulin loci. Moreover, analysis of the precise chromosomal breakpoints reveals 2 distinct cluster breakpoint regions (CBRs) within either CD274 (CBR1) or PDCD1LG2 (CBR2). To determine the phenotypic consequences of these SRs, we performed immunohistochemistry for CD274 and PDCD1LG2 on primary pretreatment biopsies and found that PDL SRs are significantly associated with PDL protein expression. Finally, stable ectopic expression of wild-type PDCD1LG2 and the PDCD1LG2-IGHV7 81 fusion showed, in coculture, significantly reduced T-cell activation. Taken together, our data demonstrate the complementary utility of fluorescence in situ hybridization and capture sequencing approaches and provide a classification scheme for PDL SRs with implications for future studies using PDL immune checkpoint inhibitors in B-cell lymphomas. PMID- 27268265 TI - White Light Emission from Planar Remote Phosphor Based on NHC Cycloplatinated Complexes. AB - We report on the generation of bright white luminescence through solid-state illumination of remote phosphors based on novel cycloplatinated N-heterocyclic carbene (NHC) compounds. Following a stepwise protocol we got the new NHC compound [{Pt(MU-Cl)(C(?)C*)}2] (4) (HC(?)C*-kappaC* = 1-(4 (ethoxycarbonyl)phenyl)-3-methyl-1H-imidazol-2-ylidene), which was used together with the related ones 4a (HC(?)C*-kappaC*= 1-(4-cyanophenyl)-3-methyl-1H-imidazol 2-ylidene) and 4b (HC(?)C*-kappaC*= 3-methyl-1-(naphthalen-2-yl)-1H-imidazol-2 ylidene) as starting materials for the synthesis of the new ionic derivatives [Pt(R-C(?)C*) (CNR')2]PF6 (R = -COOEt, R' = t-Bu (5), Xyl (6); R = -CN, R' = t-Bu (7), Xyl (8); R(?)C = Naph, R' = t-Bu (9), Xyl (10)). The X-ray structures of 6 and 8-10 have been determined. The photophysical properties of these cationic compounds have been studied and supported by the time-dependent-density functional theory (TD-DFT) calculations. The compounds 5, 8, and 9 have been revealed as the most efficient emitters in the solid state with quantum yields of 41%, 21%, and 40%, respectively. White-light remote-phosphors have been prepared just by stacking different combinations of these compounds and [Pt(bzq) (CN) (CN(t)Bu)] (R1) as blue (5, 8), yellow (9), and red (R1) components onto the same substrate. The CCT (correlated color temperature) and the CRI (color rendering index) of the emitted white-light have been tuned by accurately controlling the individual contributions. PMID- 27268264 TI - Atg7 suppression enhances chemotherapeutic agent sensitivity and overcomes stroma mediated chemoresistance in acute myeloid leukemia. AB - Autophagy is a cellular adaptive mechanism to stress, including that induced by chemotherapeutic agents. Reverse phase protein array suggested that high expression of the essential autophagy-related protein, Atg7, was associated with shorter remission in newly diagnosed acute myeloid leukemia (AML) patient samples, indicating a role in chemoresistance. Knockdown of Atg7 in AML cells using short hairpin RNA markedly increased apoptosis and DNA damage following treatment with cytarabine and idarubicin. Interestingly, coculture of AML cells with stromal cells increased autophagy and chemoresistance in the AML cells exposed to chemotherapeutic agents, and this was reversed following Atg7 knockdown. This effect was further enhanced by concomitant knockdown of Atg7 in both AML and stromal cells. These findings strongly suggest that Atg7, and likely microenvironment autophagy in general, plays an important role in AML chemoresistance. Mechanistic studies revealed that Atg7 knockdown induced a proapoptotic phenotype in AML cells, which was manifested by an increased NOXA expression at the transcriptional level. Finally, in a mouse model of human leukemia, Atg7 knockdown extended overall survival after chemotherapy. Thus, the inhibition of Atg7 appears to be a valid strategy to enhance chemosensitivity, and it could indeed improve outcomes in AML therapy. PMID- 27268266 TI - Antioxidant and antimutagenic potential of Psidium guajava leaf extracts. AB - Fruits, vegetables and medicinal herbs rich in phenolics antioxidants contribute toward reduced risk of age-related diseases and cancer. In this study, Psidium guajava leaf extract was fractionated in various organic solvents viz. petroleum ether, benzene, ethyl acetate, ethanl and methanol and tested for their antioxidant and antimutagenic properties. Methanolic fraction showed maximum antioxidant activity comparable to ascorbic acid and butylated hydroxyl toluene (BHT) as tested by DPPH free radical scavenging, phosphomolybdenum, FRAP (Fe3 + reducing power) and CUPRAC (cupric ions (Cu2+) reducing ability) assays. The fraction was analyzed for antimutagenic activities against sodium azide (NaN3), methylmethane sulfonate (MMS), 2-aminofluorene (2AF) and benzo(a)pyrene (BP) in Ames Salmonella tester strains. The methanol extracted fraction at 80 MUg/ml concentration inhibited above 70% mutagenicity. Further, phytochemical analysis of methanol fraction that was found to be most active revealed the presence of nine major compounds by gas chromatography-mass spectrometry (GC-MS). This data suggests that guava contains high amount of phenolics responsible for broad spectrum antimutagenic and antioxidant properties in vitro and could be potential candidates to be explored as modern phytomedicine. PMID- 27268267 TI - Electron Paramagnetic Resonance Characterization of Three Iron-Sulfur Clusters Present in the Nitrogenase Cofactor Maturase NifB from Methanocaldococcus infernus. AB - NifB utilizes two equivalents of S-adenosyl methionine (SAM) to insert a carbide atom and fuse two substrate [Fe-S] clusters forming the NifB cofactor (NifB-co), which is then passed to NifEN for further modification to form the iron molybdenum cofactor (FeMo-co) of nitrogenase. Here, we demonstrate that NifB from the methanogen Methanocaldococcus infernus is a radical SAM enzyme able to reductively cleave SAM to 5'-deoxyadenosine radical and is competent in FeMo-co maturation. Using electron paramagnetic resonance spectroscopy we have characterized three [4Fe-4S] clusters, one SAM binding cluster, and two auxiliary clusters probably acting as substrates for NifB-co formation. Nitrogen coordination to one or more of the auxiliary clusters in NifB was observed, and its mechanistic implications for NifB-co dissociation from the maturase are discussed. PMID- 27268268 TI - Retinal features in Mulvihill-Smith syndrome. AB - BACKGROUND: Mulvihill-Smith syndrome is a rare progeroid syndrome of sporadic nature. Previously reported ophthalmological findings include astigmatism, myopia, endothelial dystrophy, keratoconus, cataract, band keratopathy, meibomian gland dysfunction, dry eye disease, amblyopia, and allergic conjunctivitis. MATERIALS AND METHODS: The proband, a 25-year-old male subject diagnosed with Mulvihill-Smith syndrome in childhood developed retinal changes with onset of adulthood. The retinal changes were monitored for progression with fundus photography, electrodiagnostic tests, and spectral domain optical coherence tomography. RESULTS: The fundus examination revealed grossly normal looking retina with dull foveal reflex. The optical coherence tomography scan of the retina revealed diffuse thickening, schisis, and folding of retinal layers in both eyes. The structural changes in retina were progressive with wrinkling of inner retinal layers and loss of foveal contour as observed over 3 years. The electrodiagnostic tests revealed normal photoreceptor-retinal pigment epithelial interface. CONCLUSIONS: This is the first report of retinal features in Mulvihill Smith syndrome. These ocular changes coincided with other systemic changes with the onset of adulthood. These changes may indicate the natural history of retinal features in this progeria syndrome with short life span. The detailed analysis and progression of structural changes in retina is possible with optical coherence tomography. PMID- 27268269 TI - Neofiscalin A and fiscalin C are potential novel indole alkaloid alternatives for the treatment of multidrug-resistant Gram-positive bacterial infections. AB - Ten indole alkaloids were obtained from the marine sponge-associated fungus Neosartorya siamensis KUFA 0017. We studied the antimicrobial properties of these and of three other compounds previously isolated from the soil fungus N. siamensis KUFC 6349. Only neofiscalin A showed antimicrobial activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE); with a minimum inhibitory concentration (MIC) of 8 MUg mL(-1) against both strains. Another compound, fiscalin C, presented synergistic activity against MRSA when combined with oxacillin, although alone showed no antibacterial effect. Moreover, neofiscalin A, when present at sub-MICs, hampered the ability of both MRSA and VRE strains to form a biofilm. Additionally, the biofilm inhibitory concentration values of neofiscalin A against the MRSA and VRE isolates were 96 and 80 MUg mL( 1), respectively. At a concentration of 200 MUg mL(-1), neofiscalin A was able to reduce the metabolic activity of the biofilms by ~50%. One important fact is that our results also showed that neofiscalin A had no cytotoxicity against a human brain capillary endothelial cell line. PMID- 27268270 TI - An ABC transporter involved in the control of streptomycin production in Streptomyces griseus. AB - We screened for a gene that inhibits streptomycin production in Streptomyces griseus when it is introduced on a high-copy-number plasmid pIJ702, and obtained a plasmid pKM545. The introduction of pKM545 abolished streptomycin production on all media tested including YMP-sugar and Nutrient broth. S1 protection analysis demonstrated that the introduction of this plasmid downregulated the transcriptional activity of the promoter preceding strR, the pathway-specific transcriptional regulator for streptomycin biosynthesis. The 2.8-kb BamHI fragment cloned onto pKM545 contained two coding sequences SGR_5442 and 5443. These coding sequences and the two downstream ones (SGR_5444 and 5445) constituted a possible operon structure designated to be rspABCD (regulation of streptomycin production). RspB and RspC exhibited a marked similarity with an ATP binding domain and a membrane-associating domain of an ABC-2 type transporter, respectively, suggesting that the Rsp proteins comprise a membrane exporter. The gene cluster consisting of the rsp operon and the upstream divergent small coding sequence (SGR_5441) was widely distributed to Streptomyces genome. An rspB mutant of S. griseus produced 3-fold streptomycin of the parental strain in YMP liquid medium. The evidence implies that the Rsp translocator is involved in the export of a substance that specifies the expression level of streptomycin biosynthesis genes in S. griseus. PMID- 27268271 TI - Biometry and visual function of a healthy cohort in Leipzig, Germany. AB - BACKGROUND: Cross-sectional survey of ocular biometry and visual function in healthy eyes across the life span of a German population aged 20 to 69 years (n = 218). Subject number in percent per age category reflected the percentage within the respective age band of the population of Leipzig, Germany. METHODS: Measurements obtained: subjective and objective refraction, best-corrected visual acuity, accommodation, contrast sensitivity, topography and pachymetry with Scheimpflug camera, axial length with non-contact partial coherence interferometry, and spectral-domain optical coherence tomography of the retina. Pearson correlation coefficients with corresponding p-values were given to present interrelationships between stature, biometric and refractive parameters or their associations with age. Two-sample T-tests were used to calculate gender differences. The area under the logarithmic contrast sensitivity function (AULCSF) was calculated for the analysis of contrast sensitivity as a single figure across a range of spatial frequencies. RESULTS: The results of axial length (AL), anterior chamber depth (ACD) and anterior chamber volume (ACV) differed as a function of the age of the participants (rho (p value): AL -0.19 (0.006), ACD -0.56 (< 0.001), ACV-0.52 (< 0.001)). Longer eyes had deeper ACD (AL:ACD 0.62 (< 0.001), greater ACV (AL:ACV 0.65 (< 0.001) and steeper corneal radii (AL:R1ant; R2ant; R1post; R2post 0.40; 0.35; 0.36; 0.36 (all with (< 0.001)). Spherical equivalent was associated with age (towards hyperopia: 0.34 (< 0.001)), AL (-0.66 (< 0.001)), ACD (-0.52 (< 0.001)) and ACV (-0.46 (< 0.001)). Accommodation was found lower for older subjects (negative association with age, r = -0.82 (< 0.001)) and contrast sensitivity presented with smaller values for older ages (AULCSF -0.38, (< 0.001)), no change of retinal thickness with age. 58 % of the study cohort presented with a change of refractive correction above +/ 0.50 D in one or both eyes (64 % of these were habitual spectacle wearers), need for improvement was present in the young age-group and for older subjects with increasing age. CONCLUSION: Biometrical data of healthy German eyes, stratified by age, gender and refractive status, enabled cross-comparison of all parameters, providing an important reference database for future patient-based research and specific in-depth investigations of biometric data in epidemiological research. TRIAL REGISTRATION: ClinicalTrials.gov # NCT01173614 July 28, 2010. PMID- 27268273 TI - Structural snapshots of the catalytic cycle of the phosphodiesterase Autotaxin. AB - Autotaxin (ATX) is a secreted phosphodiesterase that produces the signalling lipid lysophosphatidic acid (LPA). The bimetallic active site of ATX is structurally related to the alkaline phosphatase superfamily. Here, we present a new crystal structure of ATX in complex with orthovanadate (ATX-VO5), which binds the Ogamma nucleophile of Thr209 and adopts a trigonal bipyramidal conformation, following the nucleophile attack onto the substrate. We have now a portfolio of ATX structures we discuss as intermediates of the catalytic mechanism: the new ATX-VO5 structure; a unique structure where the nucleophile Thr209 is phosphorylated (ATX-pThr). Comparing these to a complex with the LPA product (ATX LPA) and with a complex with a phosphate ion (ATX-PO4), that represent the Michaelis complex of the reaction, we observe movements of Thr209, changes in the relative displacement of the zinc ions, and a water molecule that likely fulfils the second nucleophilic attack. We propose that ATX follows the associative two step in-line displacement mechanism. PMID- 27268274 TI - Bronchoscopic Cryotherapy. Clinical Applications of the Cryoprobe, Cryospray, and Cryoadhesion. AB - Cryotherapy is an evolving therapeutic and diagnostic tool used during bronchoscopy. Through rapid freeze-thaw cycles, cryotherapy causes cell death and tissue necrosis or tissue adherence that can be used via the flexible or rigid bronchoscope. This extreme cold can be used through the working channel of the bronchoscope via a specialized cryoprobe or directly with the use of spray cryotherapy. These properties allow for multiple bronchoscopic techniques, each with its own equipment and procedural, safety, and efficacy considerations. Bronchoscopic cryotherapy can be used in a variety of clinical scenarios, including the treatment of malignant and benign central airway obstruction and low-grade airway malignancy, foreign body removal or cryoextraction, endobronchial biopsy, and transbronchial biopsy. The bulk of the experience with bronchoscopic cryotherapy consists of uncontrolled case series of malignant central airway obstruction. There are also controlled data supporting the use of cryoadhesion for endobronchial biopsies, albeit with an increased risk of controllable bleeding. The use of cryoadhesion for transbronchial biopsies is an active area of investigation with limited controlled data. In addition, there are promising future directions using bronchoscopic cryotherapy, including chemosensitizing malignancy with cryotherapy and capitalizing on the synergy between cryotherapy and radiation. PMID- 27268272 TI - Detection of cases of progressive multifocal leukoencephalopathy associated with new biologicals and targeted cancer therapies from the FDA's adverse event reporting system. AB - OBJECTIVE: To identify and summarize FDA's Adverse Event Reporting System (FAERS) cases of progressive multifocal leukoencephalopathy (PML) associated with biological and targeted cancer therapies (BTCT) that were approved between 2009 and 2015. METHODS: FAERS was searched using each BTCT name as primary or secondary suspect drug and the adverse reaction of PML. Among BTCTs with >2 case reports of PML, proportional reporting ratios (PRR) and 95% confidence intervals (CI) were calculated. RESULTS: Among 49 new BTCTs, 82 cases of PML were found for 16 drugs. Significant PRR signals were found among 7 (14.6%) BTCTs including: brentuximab (24.5, CI:14.8-40.6), ofatumumab (16.3, CI:9.6-27.4), alemtuzumab (9.9, CI:6.0-16.4), obinutuzumab (7.4, CI:2.4-22.8), ibrutinib (5.6 CI:3.0-10.5), belimumab (4.5 CI:2.3-9.0), and idelalisib (4.1, CI:1.3-12.6). Among the 82 cases with significant signals, confirmation of the diagnosis of PML using objective criteria was found in 56% of the cases. A limitation of FAERS data is that missing data are common. CONCLUSIONS: When using BTCTs, clinicians and patients consider the risk of PML versus the therapeutic benefit, particularly when used in combination with other drugs which may cause PML, such as rituximab. It is important to recognize that PML may occur in some conditions, such as chronic lymphocytic leukemia, regardless of drug therapy. PMID- 27268275 TI - Cognitive dysfunction and work productivity in major depressive disorder. AB - INTRODUCTION: Major depressive disorder (MDD) is strongly associated with poor work-related outcomes. Cognitive dysfunction is prevalent in MDD, and research supports a correlation between greater depression severity and more pronounced cognitive deficits, which frequently persist after remission. AREAS COVERED: Given the prevalence of cognitive dysfunction, and the humanistic and economic impact of occupational impairments in individuals with MDD, the relationship between cognitive dysfunction in MDD and work-related outcomes requires characterization. A selective review of the literature was conducted to better understand and further highlight this relationship. Expert commentary: Although current evidence is limited, MDD-related cognitive dysfunction may have a direct negative impact on work productivity. Presenteeism is the key outcome impacted by cognitive deficits in MDD. Additional well-designed prospective observational research may clarify how cognitive dysfunction influences the MDD-work productivity relationship. Use of reliable, valid, and sensitive measures of cognitive functioning and work productivity in MDD is warranted. PMID- 27268276 TI - How compliant are in vitro fertilization member clinics in following embryo transfer guidelines? An analysis of 59,689 fresh first in vitro fertilization autologous cycles from 2011 to 2012. AB - OBJECTIVE: To determine whether IVF clinics are compliant with American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) (ASRM/SART) guidelines and assess the multiple pregnancy outcomes according to the number of embryos transferred. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): Data from 59,689 fresh first autologous IVF cycles from the 2011-2012 SART registry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Percentage of compliant cycles, multiple pregnancy rate (PR). RESULT(S): Between 2011 and 2012, a total of 59,689 fresh first autologous cycles were analyzed. Among cleavage-stage ET cycles, the noncompliance rate ranged from 10%-27.4% depending on the age group. The multiple PR was significantly increased in noncompliant cycles involving patients <35 years (38.1% vs. 28.7%) and 35-37 years (35.4% vs. 24.5%) compared with compliant cycles. Among blastocyst-stage ET cycles, the highest rate of noncompliance was seen in patients <35 years old (71%), which resulted in a statistically higher multiple PR (48.3% vs. 2.8%) compared with compliant cycles. Far fewer cycles were noncompliant in patients 35-40 years of age. In a subanalysis of compliant cycles, transferring two blastocyst embryos in patients 35-37 years and 38-40 years resulted in a higher live birth rate compared with the transfer of one embryo (50.4% vs. 40.9% and 42.1% vs. 30.0%, respectively) but the multiple PR was also significantly higher (40.5% vs. 1.7% and 34.0% vs. 2.0%, respectively). CONCLUSION(S): Most first fresh autologous IVF cycles performed from 2011-2012 were compliant with ASRM/SART guidelines, except those that involved a blastocyst ET in patients <35 years. Despite compliance, cycles that involved the transfer of >1 embryo resulted in a high multiple PR, whereas noncompliant cycles resulted in an even more remarkable multiple PR for both cleavage and blastocyst-stage embryos. Clinics need to be more compliant with ET limits and ASRM/SART need to consider revising their guidelines to limit the number of blastocyst transfer to one in patients <=40 years of age undergoing their first IVF cycle. Furthermore, decreasing the number of cleavage-stage embryos transferred in patients <=40 years of age should also be considered. PMID- 27268277 TI - Retention of Women Faculty in Academia: Ensuring Success. PMID- 27268278 TI - Kicking modality during erratic-dynamic and static condition effects the muscular co-activation of attacker. AB - The purpose of the study was to investigate the effect of different kicking modality, i.e., erratic-dynamic target (EDT) versus static target (ST) on the performance of the roundhouse kick in two groups of taekwondo athletes of different skill level. Three-dimensional analysis and surface electromyography (SEMG) analysis were performed on 12 (Group A: six sub-elite, Group B: six elite) athletes to investigate muscle co-activation pattern under two conditions, i.e., EDT versus ST. In the results, the muscle recruitment ratio of the agonistic muscles was higher for Group A, whereas Group B had higher recruitment ratio for antagonist muscles. Overall, the co-activation index (CI) of hip joints appeared higher in the extensors for Group A, whereas higher CI was observed in flexor muscles for Group B with comparatively higher CI during EDT condition than ST condition. Higher value of CI was observed in flexor muscles of the knee joints among Group A during EDT conditions, in contrast, higher CI in the extensor muscles was observed among Group B during ST conditions. In conclusion, the study confirmed that erratic-dynamic movements of target could change the movement coordination pattern to maintain the joint stability of participants. PMID- 27268280 TI - Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria. AB - Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed. Antidepressants in vivo treatment modified the activities of selected enzymes of different mitochondria, leading to metabolic modifications in the energy metabolism of brain cortex: (a) the enhancement of cytochrome oxidase activity on somatic mitochondria; (b) the decrease of malate, succinate dehydrogenase and glutamate-pyruvate transaminase activities of synaptic mitochondria; (c) the selective effect of fluoxetine on enzymes related to glutamate metabolism. These results overcome the conflicting data so far obtained with antidepressants on brain energy metabolism, because the enzymatic analyses were made on mitochondria with diversified neuronal in vivo localization, i.e. on somatic and synaptic. This research is the first investigation on the pharmacodynamics of antidepressants studied at subcellular level, in the perspective of (i) assessing the role of energy metabolism of cerebral mitochondria in animal models of mood disorders, and (ii) highlighting new therapeutical strategies for antidepressants targeting brain bioenergetics. PMID- 27268279 TI - KAT8 Regulates Androgen Signaling in Prostate Cancer Cells. AB - Androgen receptor (AR) plays pivotal roles in prostate cancer. Upon androgen stimulation, AR recruits the Protein kinase N1 (PKN1), which phosphorylates histone H3 at threonine 11, with subsequent recruitment of tryptophan, aspartic acid (WD) repeat-containing protein 5 (WDR5) and the su(var)3-9, enhancer of zeste, trithorax/mixed-lineage leukemia (SET1/MLL) histone methyltransferase complex to promote AR target gene activation and prostate cancer cell growth. However, the underlying mechanisms of target gene activation and cell growth subsequent to WDR5 recruitment are not well understood. Here, we demonstrate an epigenetic cross talk between histone modifications and AR target gene regulation. We discovered that K(lysine) acetyltransferase 8 (KAT8), a member of the MOZ, YBF2/SAS2, and TIP 60 protein 1 (MYST) family of histone acetyltransferases that catalyzes histone H4 lysine 16 acetylation, colocalized with WDR5 at AR target genes, resulting in hormone-dependent gene activation in prostate cancer cells. PKN1 or WDR5 knockdown severely inhibited KAT8 association with AR target genes and histone H4 lysine 16 acetylation upon androgen treatment. Knockdown of KAT8 significantly decreased AR target gene expression and prostate cancer cell proliferation. Collectively, these data describe a trans histone modification pathway involving PKN1/histone H3 threonine 11 phosphorylation followed by WDR5/MLL histone methyltransferase and KAT8/histone acetyltransferase recruitment to effect androgen-dependent gene activation and prostate cancer cell proliferation. PMID- 27268281 TI - iTRAQ technology-based identification of human peripheral serum proteins associated with depression. AB - Clinical depression is one of the most common and debilitating psychiatric disorders and contributes to increased risks of disability and suicide. Differentially expressed serum proteins may serve as biomarkers for diagnosing depression. In this study, samples from depressed patients are aggregated into a pool (22*100MUL serum was used) and samples from healthy volunteers are aggregated into the other pool (20*100MUL serum was used). Isobaric tag for relative and absolute quantitation (iTRAQ) technology and tandem mass spectrometry were employed to screen for differentially expressed serum protein in two separate pools. We identified 472 proteins in the serum samples, and 154 of these presented differences in abundance between the depression and control groups. Ingenuity pathway analysis (IPA) was employed to identify the highest scoring proteins in signaling pathway networks. Finally, four differentially expressed proteins were validated by enzyme-linked immuno sorbent assay (ELISA). Proteomic studies revealed that levels of c-reaction protein (CRP), inter-alpha trypsin inhibitor heavy chain H4 (ITIH4), serum amyloid A1 (SAA1) and angiopoietin-like 3 (ANGPTL3) were substantially increased in depressed patients compared with the healthy control group. Therefore, these differentially expressed proteins may represent potential markers for the clinical diagnosis of depression. PMID- 27268283 TI - Mobile Health for All: Public-Private Partnerships Can Create a New Mental Health Landscape. AB - Research has already demonstrated that different mHealth approaches are feasible, acceptable, and clinically promising for people with mental health problems. With a robust evidence base just over the horizon, now is the time for policy makers, researchers, and the private sector to partner in preparation for the near future. The Lifeline Assistance Program is a useful model to draw from. Created in 1985 by the U.S. Federal Communications Commission (FCC), Lifeline is a nationwide program designed to help eligible low-income individuals obtain home phone and landline services so they can pursue employment, reach help in case of emergency, and access social services and healthcare. In 2005, recognizing the broad shift towards mobile technology and mobile-cellular infrastructure, the FCC expanded the program to include mobile phones and data plans. The FCC provides a base level of federal support, but individual states are responsible for regional implementation, including engagement of commercial mobile phone carriers. Given the high rates of disability and poverty among people with severe mental illness, many are eligible to benefit from Lifeline and research has shown that a large proportion does in fact use this program to obtain a mobile phone and data plan. In the singular area of mobile phone use, the gap between people with severe mental illness and the general population in the U.S. is vanishing. Strategic multi-partner programs will be able to grant access to mHealth for mental health programs to those who will not be able to afford them-arguably, the people who need them the most. Mobile technology manufacturing costs are dropping. Soon all mobile phones in the marketplace, including the more inexpensive devices that are made available through subsidy programs, will have "smart" capabilities (ie, internet connectivity and the capacity to host apps). Programs like Lifeline could be expanded to include mHealth resources that capitalize on "smart" functions, such as secure/encrypted clinical texting programs and mental health monitoring and illness-management apps. Mobile phone hardware and software development companies could be engaged to add mHealth programs as a standard component in the suite of tools that come installed on their mobile phones; thus, in addition to navigation apps, media players, and games, the new Android or iPhone could come with guided relaxation videos, medication reminder systems, and evidence-based self-monitoring and self-management tools. Telecommunication companies could be encouraged to offer mHealth options with their data plans. Operating system updates pushed out by the mobile carrier companies could come with optional mHealth applications for those who elect to download them. In the same manner in which the Lifeline Assistance Program has helped increase access to fundamental opportunities to so many low-income individuals, innovative multi partner programs have the potential to put mHealth for mental health resources in the hands of millions in the years ahead. PMID- 27268282 TI - Promoting protection against a threat that evokes positive affect: The case of heat waves in the United Kingdom. AB - Heat waves can cause death, illness, and discomfort, and are expected to become more frequent as a result of climate change. Yet, United Kingdom residents have positive feelings about hot summers that may undermine their willingness to protect themselves against heat. We randomly assigned United Kingdom participants to 1 of 3 intervention strategies intended to promote heat protection, or to a control group. The first strategy aimed to build on the availability heuristic by asking participants to remember high summer temperatures, but it elicited thoughts of pleasantly hot summer weather. The second strategy aimed to build on the affect heuristic by evoking negative affect about summer temperatures, but it evoked thoughts of unpleasantly cold summer weather. The third strategy combined these 2 approaches and succeeded in evoking thoughts of unpleasantly hot summer weather. Across 2 experiments, the third (combined) strategy increased participants' expressed intentions to protect against heat compared with the control group, while performing at least as well as the 2 component strategies. We discuss implications for developing interventions about other "pleasant hazards." (PsycINFO Database Record PMID- 27268284 TI - The role of TGF-beta-activated kinase 1 in db/db mice and high glucose-induced macrophage. AB - Accumulating evidence reveals that inflammation plays a vital part in the development of diabetic nephropathy (DN), little information is available about the TGF-beta-activated kinase 1 (TAK1) signal pathway activating inflammatory response in DN. We used bone marrow-derived macrophages (BMMs) and db/db mice to investigate the potential protective effects and mechanisms of TAK1 inhibitor (5Z 7-oxozeaenol) on diabetic kidney disease. The study showed that pretreatment with 5Z-7-oxozeaenol not only remarkably decreased high glucose (HG) stimulated excessive release of MCP-1 and TNF-alpha, but also significantly down-regulated ERK1/2, p38MAPK phosphorylation, and NF-kappaB activation in macrophages. In consistent, 5Z-7-oxozeaenol markedly reduced diabetes-induced albuminuria, histological changes, macrophage infiltration, and renal inflammatory cytokines expression and exerted its function through down-regulating ERK1/2, p38MAPK, NF kappaB activation in the kidneys of db/db mice. Our findings may provide a novel direction to study the molecular mechanism and a perspective intervention to halt the progression of DN. PMID- 27268285 TI - Tumor necrosis factor-alpha modifies the effects of Shiga toxin on glial cells. AB - Shiga toxin (STX) is one of the main factors inducing hemorrhagic colitis and hemolytic-uremic syndrome (HUS) in infections with STX-producing Escherichia coli (STEC). Approximately 62% of patients with HUS showed symptoms of encephalopathy in the 2011 Japanese outbreak of STEC infections. At that time, we reported elevated serum concentrations of tumor necrosis factor (TNF)-alpha in patients with acute encephalopathy during the HUS phase. In the current study, we investigated whether TNF-alpha augments the effects of STX in glial cell lines and primary glial cells. We found that TNF-alpha alone or STX in combination with TNF-alpha activates nuclear factor-kappaB (NF-kappaB) signaling and inhibits growth of glial cells. The magnitude of the NF-kappaB activation and the inhibition of cell growth by the STX and TNF-alpha combination was greater than that obtained with TNF-alpha alone or STX alone. Thus, this in vitro study reveals the role of TNF-alpha in glial cells during STEC infections. PMID- 27268287 TI - From Genetic Mapping to Molecular Breeding: Genomics Have Paved the Highway. PMID- 27268288 TI - Identification of differentially expressed reproductive and metabolic proteins in the female abalone (Haliotis laevigata) gonad following artificial induction of spawning. AB - Inefficient control of temperate abalone spawning prevents pair-wise breeding and production of abalone with highly marketable traits. Traditionally, abalone farmers have used a combination of UV irradiation and application of temperature gradients to the tank water to artificially induce spawning. Proteins are known to regulate crucial processes such as respiration, muscle contraction, feeding, growth and reproduction. Spawning as a pre-requisite of abalone reproduction is likely to be regulated, in part, by endogenous proteins. A first step in elucidating the mechanisms that regulate spawning is to identify which proteins are directly involved during spawning. The present study examined protein expression following traditional spawning induction in the Haliotis laevigata female. Gonads were collected from abalone in the following physiological states: (1) spawning; (2) post-spawning; and (3) failed-to-spawn. Differential protein abundance was initially assessed using two-dimensional difference in-gel electrophoresis coupled with mass spectrometry for protein identification. A number of reproductive proteins such as vitellogenin, vitelline envelope zona pellucida domain 29 and prohibitin, and metabolic proteins such as thioredoxin peroxidase, superoxide dismutase and heat shock proteins were identified. Differences in protein abundance levels between physiological states were further assessed using scheduled multiple reaction monitoring mass spectrometry. Positive associations were observed between the abundance of specific proteins, such as heat shock cognate 70 and peroxiredoxin 6, and the propensity or failure to spawn in abalone. These findings have contributed to better understand both the effects of oxidative and heat stress over abalone physiology and their influence on abalone spawning. PMID- 27268289 TI - Gastrointestinal bleeding secondary to trimethoprim-sulfamethoxazole-induced vitamin K deficiency. AB - There is a well-known association between vitamin K deficiency and haemorrhagic events including gastrointestinal bleeding. There is also a well-known association between both poor dietary intake of vitamin K and chronic antibiotic use and the development of vitamin K deficiency. Although the medical literature notes that cephalosporin antibiotics have a propensity to cause vitamin K deficiency due to the molecular structure of the medications and their ability to suppress the synthesis of clotting factors, there are other antibiotics that have also been implicated in the development of vitamin K deficiency. There are very few reports of trimethoprim/sulfamethoxazole causing vitamin K deficiency and further leading to bleeding episodes. We present such a case and discuss the risk factors leading to such complications. PMID- 27268286 TI - Combinatorial strategies for combating invasive fungal infections. AB - Invasive fungal infections are an important cause of human mortality and morbidity, particularly for immunocompromised populations. However, there remains a paucity of antifungal drug treatments available to combat these fungal pathogens. Further, antifungal compounds are plagued with problems such as host toxicity, fungistatic activity, and the emergence of drug resistance in pathogen populations. A promising therapeutic strategy to increase drug effectiveness and mitigate the emergence of drug resistance is through the use of combination drug therapy. In this review we describe the current arsenal of antifungals in medicine and elaborate on the benefits of combination therapy to expand our current antifungal drug repertoire. We examine those antifungal combinations that have shown potential against fungal pathogens and discuss strategies being employed to discover novel combination therapeutics, in particular combining antifungal agents with non-antifungal bioactive compounds. The findings summarized in this review highlight the promise of combinatorial strategies in combatting invasive mycoses. PMID- 27268290 TI - Limb salvage following iatrogenic arterial injury: complications of cardiac support using intra-aortic balloon pumps. AB - This is a unique case report describing complex limb salvage in a patient who experienced acute limb ischaemia due to a complication of intra-aortic balloon pump (IABP) counterpulsation. This case focuses on a patient who had an IABP counterpulsation device inserted following myocardial infarction, requiring urgent coronary artery bypass grafting for acute coronary syndrome. Postoperatively, the IABP could not be removed, with consequent iliac thrombosis and acute limb ischaemia. Emergency femoral-to-femoral crossover bypass was performed using a polytetrafluoroethylene graft. A portion of the IABP balloon tip was entrapped and retained, however, and became the focus of delayed septicaemia, resulting in graft infection and wound breakdown 6 weeks later. Explantation of the residual balloon tip, ligation of the right external iliac artery and redo femoral-femoral crossover using the great saphenous vein were successfully performed. PMID- 27268291 TI - HTLV-1-associated myelopathy in a solid organ transplant recipient. AB - Human T-cell lymphotropic virus type-1 (HTLV-1) is endemic in Japan, the Caribbean and in South American countries such as Ecuador. This virus is the cause of HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), a myelopathy characterised by chronic progressive paraparesis, spasticity and urinary symptoms. We report the case of a 40-year-old man who received a kidney transplant from a living donor and developed HAM/TSP, 24 months after transplant. The diagnosis was confirmed by detection of HTLV-1 in blood and cerebrospinal fluid by the ELISA and Western Blot tests. For myelopathy, the patient was treated with pulse methylprednisolone, but had poor response to treatment. We recommend that all patients receiving transplants and their donors who come from endemic countries be given a mandatory screening for HTLV-1 through an ELISA test, in an effort to inform candidates for renal transplantation of the potential risk of infection and the development of this disease. PMID- 27268292 TI - Skin rash: a manifestation of early congenital syphilis. PMID- 27268293 TI - Reply to letter to the editor - Mechanical ventilation in idiopathic pulmonary fibrosis: Unresolved dilemma. PMID- 27268294 TI - Hepatitis C reinfection following treatment induced viral clearance among people who have injected drugs. AB - BACKGROUND: Although people who inject drugs (PWID) are an important group to receive Hepatitis C Virus (HCV) antiviral therapy, initiation onto treatment remains low. Concerns over reinfection may make clinicians reluctant to treat this group. We examined the risk of HCV reinfection among a cohort of PWID (encompassing all those reporting a history of injecting drug use) from Scotland who achieved a sustained virological response (SVR). METHODS: Clinical and laboratory data were used to monitor RNA testing among PWID who attained SVR following therapy between 2000 and 2009. Data were linked to morbidity and mortality records. Follow-up began one year after completion of therapy, ending on 31st December, 2012. Frequency of RNA testing during follow-up was calculated and the incidence of HCV reinfection estimated. Cox proportional hazards regression was used to examine factors associated with HCV reinfection. RESULTS: Among 448 PWID with a SVR, 277 (61.8%) were tested during follow-up, median 4.5 years; 191 (69%) received one RNA test and 86 (31%) received at least two RNA tests. There were seven reinfections over 410 person years generating a reinfection rate of 1.7/100py (95% CI 0.7-3.5). For PWID who have been hospitalised for an opiate or injection related cause post SVR (11%), the risk of HCV reinfection was greater [AHR=12.9, 95% CI 2.2-76.0, p=0.002] and the reinfection rate was 5.7/100py (95% CI 1.8-13.3). CONCLUSION: PWID who have been tested, following SVR, for HCV in Scotland appear to be at a low risk of reinfection. Follow-up and monitoring of this population are warranted as treatment is offered more widely. PMID- 27268295 TI - The effect of two levels of hemospermia on stallion fertility. AB - Hemospermia can occur consistently or intermittently in stallion ejaculates and may cause a reduction in the fertility of the affected ejaculate. It is unknown what amount of blood in an ejaculate leads to subfertility. This study investigated the effect of higher and lower levels of hemospermia (50% and 5%, respectively) on fertility using 24 reproductively normal mares inseminated over three consecutive estrous cycles with fresh extended semen. Mares inseminated with a 5% blood-contaminated ejaculate became pregnant at the same rate (75% per cycle; 18 of 24) as the mares inseminated with blood-free (control) semen (75% per cycle; 18 of 24). The ejaculates containing 50% blood were sterile (0% per cycle, 0 of 24). We concluded that it is the amount of blood, not the mere presence of blood, in an ejaculate that impacts fertility. PMID- 27268296 TI - Anti-Mullerian hormone (AMH) receptor type II expression and AMH activity in bovine granulosa cells. AB - Anti-Mullerian hormone (AMH) produced by granulosa cells has previously been proposed to play a role in regulating granulosa cell differentiation and follicle selection. Although AMH receptor type II (AMHR2) dimerizes with a type I receptor to initiate AMH signaling, little is known about the regulation of AMHR2 expression in bovine granulosa cells and the role of AMH in follicle development. The primary objectives of this study were to: (1) characterize AMHR2 expression in granulosa cells during follicle development; (2) identify factors that regulate AMHR2 mRNA expression in granulosa cells; and (3) examine the role of AMH signaling in granulosa cell differentiation and proliferation. Bovine granulosa cells were isolated from 5- to 8-mm follicles before selection and deviation, as well as from 9- to 12-mm and 13- to 24-mm follicles after selection. Analyses revealed that expression of AMHR2 was greater in 5- to 8-mm follicles compared with 13- to 24-mm follicles (P < 0.05). Granulosa cells treated with bone morphogenetic protein 6 (BMP6) or BMP15, but not BMP2, significantly increased AMHR2 expression when compared with control cultured cells (P < 0.05). In addition, expression of AMH was greater in granulosa cells cultured with BMP2, BMP6, or BMP15 when compared with controls (P < 0.05). Finally, treatment with recombinant human AMH, in vitro, inhibited CYP19A1 expression in a dose-related (10-100 ng/mL) fashion, and reduced granulosa cell proliferation at 48 and 72 hours (P < 0.05). Results from these studies indicate that AMH signaling plays a role in both regulating granulosa cell proliferation and preventing granulosa cells from 5- to 8-mm follicles from undergoing premature differentiation before follicle selection. PMID- 27268297 TI - Holding equine oocytes in a commercial embryo-holding medium: New perspective on holding temperature and maturation time. AB - In the present study, we examined the effect of holding equine oocytes in Syngro embryo holding medium (EHM) overnight at either 4 degrees C, 17 degrees C, or 22 degrees C to 25 degrees C, on the time to maturation and developmental competence. We also examined the effect of placing denuded oocyte without extruded polar body back in maturation condition on subsequent maturation rate. In experiment 1, cumulus-oocyte complexes (COCs) were recovered postmortem and placed in EHM at 22 degrees C to 25 degrees C for 18 to 20 hours (OH) or placed directly in maturation (DM). The maturation rate was assessed after 22, 24, or 28 hours of culture. After denuding cumulus cells at 22 or 24 hours, oocytes without obvious polar body were placed back into culture and reassessed at subsequent time points. At 22 hours, a higher proportion of oocytes placed in OH achieved nuclear maturation than those placed in DM (63% and 37%, respectively, P = 0.008). At 24 and 28 hours, no significant differences in the % MII stage oocytes were observed between OH and DM. The nuclear maturation rate for OH oocytes was similar at 22, 24, and 28 hours, indicating that the maximum maturation rate was reached at an earlier time than that in DM. Oocytes fertilized by intracytoplasmic sperm injection resulted in a 7.1% and 6.3% blastocyst rate for OH and DM, respectively. Denuding oocytes after 22 hours or more of culture did not have an adverse effect on the final nuclear maturation rate. After 28 hours of culture, the same nuclear maturation rate (MII) was reached for nondenuded oocytes and oocytes denuded after 22 hours of 24 hours of culture. In experiment 2, COCs were held overnight at room temperature in EHM, then placed in maturation for 20, 22, and 28 hours. Nuclear maturation rate was significantly lower at 20 hours than 22 and 28 hours of culture and was similar at 22 and 28 hours, suggesting that at least 22 hours of culture is required to reach maximal maturation rate for stored oocytes (43%, 62%, and 65% at 20, 22, and 28 hours, respectively. P < 0.001). In experiment 3, COCs were either placed directly in culture or held at 22 degrees C to 25 degrees C, 17 degrees C, or 4 degrees C overnight. After 24 hours of culture, maturation rate was similar for all groups, suggesting that COCs can be stored in conventional 4 degrees C transport condition or 17 degrees C. In preliminary studies, COCs were held at 4 degrees C followed by 24 hours of culture, and mature oocytes were fertilized using intracytoplasmic sperm injection. Twenty-three injected oocytes yielded four blastocysts. In conclusion, we reported that oocytes can be placed in a commercial EHM and stored overnight without a detrimental effect on maturation rates or blastocyst development. Oocytes held in holding medium require less time to reach the MII stage than oocytes placed in culture directly. Removing the cumulus cells from oocytes that have been cultured for at least 22 hours does not seem to alter the final nuclear maturation rate. Finally, we observed no detrimental effect of storing oocytes at 4 degrees C for up to 18 hours, and oocytes appeared to maintain developmental competence and blastocyst potential. PMID- 27268298 TI - Lineage switch with t(6;11)(q27;q23) from T-cell lymphoblastic lymphoma to acute monoblastic leukemia at relapse. AB - We present a patient with T-cell lymphoblastic lymphoma (T-LBL) harboring t(6;11)(q27;q23) that converted to acute monoblastic leukemia at relapse. A 27 year-old man developed T-LBL with a mediastinal mass. He exhibited several recurrences in the central nervous system and marrow. A fifth relapse occurred in the marrow, with 42.8% blasts with CD4, CD5, CD7, CD10, CD33, CD34, HLA-DR and cytoplasmic (cy) CD3. While achieving complete remission with nelarabine, sixth relapse occurred in the marrow with 6.8% blasts, which had characteristics of monoblastic features, 2 months later. Marrow blasts were positive for myeloperoxidase, CD4, CD33, CD56, CD64, and HLA-DR, but were negative for cyCD3, CD5, CD7, CD10, and CD34. Marrow cells at both the 5th lymphoid and 6th myeloid relapses had t(6;11)(q27;q23) and the same MLL-MLLT4 fusion transcript. In addition, the MLL-MLLT4 fusion sequences documented in the initial mediastinal cells were the same as seen in peripheral blood cells at the 6th relapse. The patient continues 7th remission after one course of gemtuzumab ozogamicin therapy followed by cord blood transplantation for more than 3 years. Sequential phenotypic and cytogenetic studies may yield valuable insights into the mechanism of leukemic recurrence and possible implications for treatment selection. PMID- 27268299 TI - Quasi-Racemic X-ray Structures of K27-Linked Ubiquitin Chains Prepared by Total Chemical Synthesis. AB - Quasi-racemic crystallography has been used to determine the X-ray structures of K27-linked ubiquitin (Ub) chains prepared through total chemical synthesis. Crystal structures of K27-linked di- and tri-ubiquitins reveal that the isopeptide linkages are confined in a unique buried conformation, which provides the molecular basis for the distinctive function of K27 linkage compared to the other seven Ub chains. K27-linked di- and triUb were found to adopt different structural conformations in the crystals, one being symmetric whereas the other triangular. Furthermore, bioactivity experiments showed that the ovarian tumor family de-ubiquitinase 2 significantly favors K27-linked triUb than K27-linked diUb. K27-linked triUb represents the so-far largest chemically synthesized protein (228 amino acids) that has been crystallized to afford a high-resolution X-ray structure. PMID- 27268301 TI - Variations in care quality occur across the whole week, not just at weekends. PMID- 27268300 TI - An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK. AB - A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury 'sensor', as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK. PKA is required for the induction of Wnd signaling in injured axons, and DLK is essential for the regenerative effects of cAMP in mammalian DRG neurons. These findings link two important mediators of responses to axonal injury, DLK/Wnd and cAMP/PKA, into a unified and evolutionarily conserved molecular pathway for stimulating the regenerative potential of injured axons. PMID- 27268304 TI - Field and Laboratory Dissipation of the Herbicide Fomesafen in the Southern Atlantic Coastal Plain (USA). AB - To control weeds with evolved resistance to glyphosate, Southeastern (USA) cotton farmers have increased fomesafen (5-(2-chloro-alpha,alpha,alpha-trifluoro-p tolyloxy)-N-mesyl-2-nitrobenzamide) use. To refine fomesafen risk assessments, data are needed that describe its dissipation following application to farm fields. In our study, relatively low runoff rates and transport by lateral subsurface flow, <1.0 and 0.15% of applied respectively, were observed. The low runoff rate was linked to postapplication irrigation incorporation and implementation of a common conservation tillage practice. Moderate soil persistence (t1/2 = 100 days) was indicated in laboratory incubations with surface soil, however, analysis of soil cores from treated plots showed that ~3% of fomesafen applied persisted in subsoil >3 years after application. Findings suggest low potential for fomesafen movement from treated fields, however, the fate of fomesafen that accumulated in subsoil and the identity of degradates are uncertain. Soil and water samples were screened for degradates, but, none were detected. PMID- 27268303 TI - Clinical Features of and Risk Factors for Fatal Ebola Virus Disease, Moyamba District, Sierra Leone, December 2014-February 2015. AB - The 2013-2016 outbreak of Ebola virus disease (EVD) in West Africa infected >28,000 people, including >11,000 who died, and disrupted social life in the region. We retrospectively studied clinical signs and symptoms and risk factors for fatal outcome among 31 Ebola virus-positive patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. We found a higher rate of bleeding manifestations than reported elsewhere during the outbreak. Significant predictors for death were shorter time from symptom onset to admission, male sex, high viral load on initial laboratory testing, severe pain, diarrhea, bloody feces, and development of other bleeding manifestations during hospitalization. These risk factors for death could be used to identify patients in need of more intensive medical support. The lack of fever in as many as one third of EVD cases may have implications for temperature-screening practices and case definitions. PMID- 27268305 TI - Acceptance and efficacy of interventions for family caregivers of elderly persons with a mental disorder: a meta-analysis. AB - BACKGROUND: The aim of the present study was to conduct an extended meta-analysis of the efficacy and acceptance of supportive interventions for alleviating depressive symptoms in family caregivers of elderly relatives with a mental disorder, including dementia. The second aim was to analyze intervention characteristics as potential moderators of the efficacy and acceptance of these interventions. METHODS: We searched electronic databases for randomized controlled trials (RCTs) published between 2005 and 2014. Thirty-three studies were included in the meta-analysis with a total of 5,980 participants. RESULTS: No RCTs that tested interventions for caregivers of elderly patients with mental disorders other than dementia were found. The weighted pooled effect size of the interventions for caregivers of dementia patients was positive but small (standardized mean difference = 0.13; CI0.95 [0.03; 0.23], p = 0.01). Meta regression analysis revealed higher effect sizes for interventions that were individually customized. Intervention discontinuation rates were low (mean 11%, SD = 6.3) and independent of most intervention characteristics. If the intervention was delivered via telecommunication intervention discontinuation rates tended to be higher (r = -0.39, p = 0.07). CONCLUSIONS: Comparative research for caregivers of elderly patients with mental disorders other than dementia is lacking. RCTs of interventions for family caregivers of dementia patients of the last decade show good acceptance among intervention participants, but there is still a need to improve the efficacy of these interventions. Individual customization of intervention components might enhance efficacy. More research is needed on the acceptance of telecommunication interventions for family caregivers. PMID- 27268306 TI - Clinical outcomes of adenoid cystic carcinoma of the head and neck: a single institution 20-year experience. AB - BACKGROUND: This study reports the clinical outcomes of head and neck adenoid cystic carcinoma treatment over a 20-year period. METHODS: The treatment outcome of 51 head and neck adenoid cystic carcinoma patients treated between 1992 and 2013 were analysed. Patients were stratified into radical treatment and disease control groups. RESULTS: A total of 40 patients underwent surgery and post operative radiotherapy. The 10-year disease-specific survival rate was 93 per cent. Eleven patients had tumour recurrence: of these, nine were pulmonary metastases. The 11 patients in the disease control group had a median follow up of 21 months (range, 2-172 months); 5 underwent radical radiotherapy with palliative intent. CONCLUSION: There was late tumour recurrence in over 25 per cent of patients. Adenoid cystic carcinoma has a high tendency to relapse even after radical excision and adjuvant therapy. However, definitive radiotherapy should still be considered on an individual basis because it may provide local control and prolong patient survival. PMID- 27268307 TI - Conjugation of mono and di-GalNAc sugars enhances the potency of antisense oligonucleotides via ASGR mediated delivery to hepatocytes. AB - Antisense oligonucleotides (ASOs) conjugated to trivalent GalNAc ligands show 10 fold enhanced potency for suppressing gene targets expressed in hepatocytes. Trivalent GalNAc is a high affinity ligand for the asialoglycoprotein receptor (ASGR)-a C-type lectin expressed almost exclusively on hepatocytes in the liver. In this communication, we show that conjugation of two and even one GalNAc sugar to single stranded chemically modified ASOs can enhance potency 5-10 fold in mice. Evaluation of the mono- and di-GalNAc ASO conjugates in an ASGR binding assay suggested that chemical features of the ASO enhance binding to the receptor and provide a rationale for the enhanced potency. PMID- 27268308 TI - Synthesis and biological analysis of novel glycoside derivatives of l-AEP, as targeted antibacterial agents. AB - To develop targeted methods for treating bacterial infections, the feasibility of using glycoside derivatives of the antibacterial compound l-R aminoethylphosphonic acid (l-AEP) has been investigated. These derivatives are hypothesized to be taken up by bacterial cells via carbohydrate uptake mechanisms, and then hydrolyzed in situ by bacterial borne glycosidase enzymes, to selectively afford l-AEP. Therefore the synthesis and analysis of ten glycoside derivatives of l-AEP, for selective targeting of specific bacteria, is reported. The ability of these derivatives to inhibit the growth of a panel of Gram-negative bacteria in two different media is discussed. beta-Glycosides (12a) and (12b) that contained l-AEP linked to glucose or galactose via a carbamate linkage inhibited growth of a range of organisms with the best MICs being <0.75mg/ml; for most species the inhibition was closely related to the hydrolysis of the equivalent chromogenic glycosides. This suggests that for (12a) and (12b), release of l-AEP was indeed dependent upon the presence of the respective glycosidase enzyme. PMID- 27268309 TI - Preliminary testing of the Swedish version of the Assessment of Interprofessional Team Collaboration Scale (AITCS-S). AB - Interprofessional collaboration might improve healthcare processes and outcomes; however, it has been found that most instruments that aim to measure collaboration have undergone limited testing. The assessment of interprofessional team collaboration scale (AITCS) is one questionnaire that aims to evaluate collaboration, but it has not yet been extensively tested. The aim of this study was to translate and to cross-culturally adapt the AITCS for use in Sweden, to describe floor and ceiling values, and to investigate the AITCS in terms of reliability, face, and content validity. The study included a total of 349 participants working in team-based pain rehabilitation. The participants were asked to fill in the Swedish version of the AITCS (AITCS-S) at baseline. Of these, 73 participants also completed the AITCS-S two weeks later. The results showed that the content and face validity were good. Internal consistency varied from 0.79 to 0.96 and judged to be acceptable to excellent. Test-retest stability showed excellent stability with intraclass correlation values above 0.75 for all subscales. This study concludes that the Swedish version of the AITCS is a reliable and valid questionnaire. Further psychometric investigations might be undertaken in order to attempt to develop shorter versions of the AITCS-S. PMID- 27268310 TI - Percutaneous Drainage of Chronic Destructive Lumbar Osteomyelitis Abscess Via the Use of Bilateral Transpedicular Trocar Access. AB - BACKGROUND: Pyogenic spondylodiskitis is an infection of intervertebral disks and spinal vertebral bodies. Various minimally invasive approaches to the infected disk spaces/abscesses have been described for management of early stages of the infection. Patients with chronic occurrence present with extensive infection, neurologic deficits, and bone destruction. Such patients commonly have substantial medical comorbidities. Despite the increased risks of complications, they often are treated with open surgical approaches without minimally invasive options. We describe a bilateral transpedicular approach to vertebral body abscess in a chronically infected patient with intraoperative contiguous irrigation. CASE DESCRIPTION: We present 2 cases, a 58-year-old man and a 61-year old man, both with a diagnosis of vertebral osteomyelitis. Images of lumbar spine showed epidural abscess and adjacent vertebral body destruction. Because of their poor clinical condition and chronicity of disease, these patients underwent percutaneous bilateral transpedicular approach. CONCLUSION: Patients in poor health and with chronic vertebral osteomyelitis may benefit from minimally invasive percutaneous transpedicular drainage and irrigation of the abscess, representing a minimally invasive and effective treatment alternative for these patients. PMID- 27268311 TI - Epidural Spinal Cord Stimulation: A Novel Therapy in the Treatment of Restless Legs Syndrome. AB - BACKGROUND: We report a unique finding of a patient whose restless legs syndrome (RLS) symptoms abated after the placement of a spinal cord stimulator for chronic neuropathic pain. RLS is a common disorder, with many patients unable to find sufficient relief from their symptoms. CASE DESCRIPTION: A patient diagnosed with neuropathic pain who also suffered from RLS symptoms despite medication therapy underwent implantation of a spinal cord stimulator after a successful trial. This patient was interviewed formally about his RLS symptoms immediately before his procedure and at 6 weeks, 6 months, and 2.5 years after the procedure. The patient also completed the International Restless Legs Syndrome Scale questionnaire to objectively quantify the severity of his symptoms. Finally, the patient kept a 5-day journal detailing when the stimulator was in use. The patient reported subjective symptomatic improvement in his RLS symptoms with improved sleep quality and quantity, in addition to improvement in his back pain. The patient's score on the International Restless Legs Syndrome Scale improved after implantation from 33 to 0 on a 40-point scale. Moreover, when asked to keep a journal record of his stimulator use, the patient noted that he only used the stimulator before going to bed to help his RLS symptoms and no longer required any medication for his previous RLS symptoms. CONCLUSIONS: Epidural stimulation may be an additional, alternative, or novel therapy in the treatment of RLS. PMID- 27268312 TI - Carotid Endarterectomy on Antiplatelet Agents in the Era of Point-of-Care Testing. AB - OBJECTIVE: The safety of carotid endarterectomy in patients with a response to antiplatelet agents (aspirin and clopidogrel) confirmed by point-of-care testing is unknown. Thus, we sought to determine whether using point-of-care assessment of platelet inhibition reveals risk factors for operative complications or predicts clinical outcomes. METHODS: We reviewed records of carotid endarterectomy patients treated from March 2013 to July 2015 to extract demographics, lesion characteristics, laboratory data, procedural complications, and follow-up. Administration of aspirin, clopidogrel, or therapeutic anticoagulation within 5 days before surgery was recorded. RESULTS: We analyzed 79 patients with 86 lesions (mean age 70.9 +/- 10.0 years). More patients with a P2Y12 reaction unit (PRU) <170 had neck hematomas (4/10, 40.0%) than those with a PRU >=170 (2/9, 22.2%) (P = 0.63). Estimated blood loss >=100 mL was more frequent among patients with PRU <170 (9/10, 90.0%) than among those with PRU >=170 (5/9, 55.6%) (P = 0.09). Clopidogrel use, regardless of response, independently predicted neck hematoma in a logistic regression model, with increased odds of 8.5. Mean postoperative modified Rankin Scale scores did not differ statistically between clopidogrel users and nonusers at a mean follow-up of 108.5 +/- 146.3 days (P = 0.27). CONCLUSIONS: Clopidogrel use within 5 days of carotid endarterectomy independently predicted postoperative neck hematomas, most of which were managed conservatively. Patients with PRU <170 were more likely to have estimated blood loss >=100 mL during surgery and surgery lasting >=3 hours. PMID- 27268313 TI - Subdural Hematoma Mimickers: A Systematic Review. AB - BACKGROUND: A variety of subdural pathologies that may mimic hematomas are reported in the literature. We aimed to identify the atypical clinical and radiologic presentations of subdural masses that may mimic subdural hematomas. METHODS: A systematic review of MEDLINE and Embase was conducted independently by 2 reviewers to identify articles describing subdural hematoma mimickers. We also present a patient from our institution with a subdural pathology mimicking a subdural hematoma. We analyzed patient clinical presentations, underlying pathologies, radiologic findings, and clinical outcomes. RESULTS: We included 43 articles totaling 48 patients. The mean +/- SD patient age was 55.7 +/- 16.8 years. Of the 45 cases describing patient history, 13 patients (27%) had a history of trauma. The underlying pathologies of the 48 subdural collections were 10 metastasis (21%), 14 lymphoma (29%), 7 sarcoma (15%), 4 infectious (8%), 4 autoimmune (8%), and 9 miscellaneous (19%). Findings on computed tomography (CT) scan were 18 hyperdense (41%), 11 hypodense (25%), 9 isodense (20%), 3 isodense/hyperdense (7%), and 3 hypodense/isodense (7%). Thirty-four patients (71%) were treated surgically; among these patients, 65% had symptom resolution. Neither the pathology (P = 0.337) nor the management strategy (P = 0.671) was correlated with improved functional outcomes. CONCLUSIONS: Identification of atypical history and radiologic features should prompt further diagnostic tests, including magnetic resonance imaging (MRI), to elucidate the proper diagnosis, given that certain pathologies may be managed nonsurgically. A subdural collection that is hyperdense on CT scan and hyperintense on T2-weighted MRI, along with a history of progressive headache with no trauma, may raise the suspicion of an atypical subdural pathology. PMID- 27268314 TI - Critical Age Affecting Functional Outcome after Decompressive Hemicraniectomy for Malignant Hemispheric Infarction. AB - OBJECTIVE: Although age already is known as a crucial factor affecting the functional outcome after a hemicraniectomy for malignant hemispheric infarction, previous studies have used arbitrary age cut-offs of 50, 60, or 70 years. Therefore, this study investigated predictors of the functional outcome after a hemicraniectomy and attempted to determine the critical age for an unfavorable functional outcome. METHODS: A total of 38 patients with large hemispheric infarction were treated with a decompressive hemicraniectomy and the corresponding 1-year modified Rankin Scale (mRS) data obtained. An array of clinical variables was then investigated in relation to the functional outcomes. RESULTS: A multivariate analysis that used binary multiple logistic regression revealed that advanced age was a statistically significant predictor of an unfavorable 1-year functional outcome. In a receiver operating characteristic curve analysis for age, a patient age >58 years was determined as an appropriate cut-off value for predicting an unfavorable outcome. The patients aged >58 years showed an 82% positive predictive value (PPV) for an unfavorable outcome with mRS >=4, and a 50% PPV for mRS >=5. Moreover, a patient age cutoff value of >67 years exhibited a 100% PPV for predicting an unfavorable functional outcome with mRS >=4. CONCLUSIONS: Advanced age was identified as a significant predictor of an unfavorable outcome and functional dependency. The PPV of a patient age >58 years and >67 years for predicting an unfavorable outcome with functional dependency was 82% and 100%, respectively. PMID- 27268315 TI - Long-Term Effect of Flow Diversion on Large and Giant Aneurysms: MRI-DSA Clinical Correlation Study. AB - BACKGROUND: The long-term effect of flow diversion (FD) on aneurysms has not been well studied. OBJECTIVE: We aimed to assess the effect of the Pipeline embolization device (Covidien, Irvine, California, USA) on large and giant intracranial aneurysms with magnetic resonance imaging (MRI) and digital subtraction angiography (DSA) and then correlate with clinical follow-up. METHODS: We conducted a retrospective analysis of aneurysms treated solely with Pipeline without adjunctive therapy. The largest aneurysm diameters were compared with pretreatment and post treatment MRI and correlated with DSA and clinical symptoms. RESULTS: Twelve patients harboring large and giant saccular unruptured aneurysms, treated with Pipeline, were included. Mean follow-up times were as follows: MRI 22.8 months (range 1-57), DSA 18.2 months (range 1-33), and clinical 29 months (range 1-48). Ten (83%) of 12 treated aneurysms decreased in size on MRI, which was first seen at an average of 17 months (range 4-57). In 70% of patients the change was noted on MRI <=1 year after treatment, at an average of 9.1 months (range 4-12). MRI reduction was more likely in angiographically occluded aneurysms. Five aneurysms with complete occlusion on early angiogram showed size reduction on MRI only at >=12 months. Mean aneurysm size reduction was 57% (range 19.6-94.2), which correlated well with improvement of cranial neuropathies in 75% and headaches in 100% of patients. CONCLUSION: Most aneurysms treated with Pipeline decreased in size, correlating with clinical improvement. Some aneurysms remained unchanged on MRI until a later time point despite early DSA occlusion. It may be reasonable to eliminate early postprocedural imaging and start follow-up only as late as 1 year after FD treatment in clinically stable, asymptomatic patients. PMID- 27268316 TI - Long Noncoding RNAs and Their Regulatory Network: Potential Therapeutic Targets for Adult Moyamoya Disease. AB - OBJECTIVE: To investigate long noncoding ribonucleic acid (lncRNA) expression patterns in adult moyamoya disease (MMD) patients and explore their possible roles in the pathophysiology of MMD. METHODS: A healthy control group (n = 10) and an MMD group (n = 15) were evaluated. RNA was extracted from peripheral blood samples and hybridized to microarray to get lncRNA expression profiles. Then predicted lncRNA target genes were identified, and bioinformatics analysis was performed to investigate their molecular functions. RESULTS: In the MMD group, 3649 lncRNAs exhibited more than 2-fold expression than their counterparts in the healthy control group; of these, 1494 were upregulated, while 2155 were downregulated. Principal component analysis and Hclust analysis produced completely different clusters between the 2 groups. Gene ontology and KEGG pathway enrichment analysis suggested that the differentially expressed lncRNAs regulate multiple signaling pathways that were related with inflammation and vascular disease, and mitogen-activated protein kinase (MAPK) signaling pathway was the core regulatory pathway. CONCLUSIONS: Long noncoding RNA expression profiles were quite different between MMD and control groups. Multiple signaling pathways that were closely associated with immune response, vasculogenesis, and smooth muscle contraction were indicated to participate in lncRNAs regulatory mechanism; of these, MAPK signaling pathway, which has been well studied for the treatment of many other cardiovascular diseases, was the core of this regulatory network. Our findings could help further understand the pathophysiology of MMD and provide new potential therapeutic targets. PMID- 27268317 TI - Histologic Evidence for Arteriovenous Malformation-Like Vasculature Occurring within an Intracerebral Schwannoma: A Case Report and Review of the Literature. AB - BACKGROUND: The phenomenon of intracerebral schwannoma is exceedingly rare, and its etiology still a matter of debate. No documented cases of intracerebral schwannoma containing vascular elements consistent with those of an arteriovenous malformation (AVM) have been reported. We describe such a case here. CASE DESCRIPTION: A left temporal intraparenchymal lesion was discovered incidentally in a 34-year-old man after he suffered a mild trauma. The lesion was resected and found on histologic examination to be an intracerebral schwannoma with AVM-like vasculature. The patient made a full recovery after resection. CONCLUSIONS: To our knowledge, this is the first case of an intracerebral schwannoma with AVM like characteristics to be reported in the literature. We hypothesize that the co occurrence of this rare pathologic entity is caused by an interrelated etiologic process, with the tumor microenvironment of the schwannoma inciting the development of the vascular malformation. PMID- 27268318 TI - Intraoperative Ultrasound Technology in Neuro-Oncology Practice-Current Role and Future Applications. AB - BACKGROUND: Surgery for cranial and spinal tumors has evolved tremendously over the years. Not only have neuro-oncologists been able to better understand tumor biology and thereby improve multimodality therapy, but advances in surgical techniques have also directly equipped neurosurgeons with the armamentarium necessary to achieve more radical resections safely. Intraoperative imaging tools are one such adjunct. Though intraoperative magnetic resonance (MR) has emerged as the "gold standard" among these, logistical challenges make it difficult to implement across all centers. On the other hand, the use of ultrasound (US) intraoperatively predates the use of MR. Over the past 4 decades, technologic improvements have refined and expanded the scope and application of intraoperative US technology. Strategies to maximize its efficacy and overcome the various limitations have evolved. A large volume of clinical experience has accumulated with respect to its role as an adjunct specifically in tumor surgery. METHODS: We performed a literature review to evaluate the role of IOUS in tumor surgery. This review traces the evolution of intraoperative US over the years and reviews the current scope and applications with respect to neuro-oncologic surgery, as well as potential future applications. RESULTS: IOUS has evolved over the years since its introduction. Advances in technology have provided real-time navigated and 3-D techniques, which overcome many of the limitations of older IOUS techniques. This has shown to be very useful in not only localization of lesions, but also in improving resection rates as well as survival. CONCLUSIONS: IOUS is a powerful and versatile multipurpose intraoperative adjunct in tumor surgery, especially for resection control. The learning curve is relatively easy to climb and future improvements in technology are likely to widen the scope of its use. PMID- 27268319 TI - Thirdhand tobacco smoke: procedures to evaluate cytotoxicity in cell cultures. AB - The risks associated to tobacco smoking are not ceased with smoke extinction. Many toxic compounds remain in the environment after the cigarette is extinguished and accumulated in the air or on surfaces. However, little is known about the risks of this exposure. The aim of this study was to evaluate procedures to collect thirdhand smoke (THS) and prepare the samples to perform three in vitro toxicity tests. Cellulose papers and cotton wipes were used to impregnate with nicotine solution and smoke cigarette in a chamber or in smoker's home. Samples were immersed in methanol or Dulbecco's modified Eagle's medium (DMEM) to expose Hep-2 cells. MTT, neutral red uptake (NRU) and trypan blue assays were performed. The concentration of nicotine in DMEM extract of THS in paper and cotton was similar to those in methanol extract (p > 0.05). Alterations in the mitochondrial and lysosomal functions were found in both paper and cotton samples; however, the cytotoxic effect was not always observed. There was a decrease of 21-31% in MTT assay and 38-56% in NRU assay (p < 0.003). There was a dose-response relationship between the amount of cigarettes and lysosomal viability; the correlation was higher for cotton samples (r = -0.843, p < 0.001). As a dose-response relationship was found only in NRU assay, this test may be a more suitable choice rather than the MTT assay. Paper and wipe sampling can be reliable markers of tobacco smoke contamination. Moreover, these materials, if properly prepared, can be used as substrate providers to perform cellular assays. PMID- 27268320 TI - A Novel Timesaving Method for Hepatobiliary Imaging for Suspected Acute Cholecystitis. AB - OBJECTIVE: To optimize resource utilization of cholescintigraphy for suspected acute cholecystitis with a time-saving method without a loss in diagnostic accuracy. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study. Hepatobiliary imaging data for 81 patients with suspected acute cholecystitis were recalled for modification into 2 summed static images, using only the first and last 5 minutes of the dynamic images, thereby eliminating the middle 50 minutes of imaging data. Two nuclear medicine physicians interpreted the summed images to assess visualization, and those interpretations were compared to the original reports based on using all 60 minutes of dynamic imaging. A third nuclear medicine physician mediated rare inter-reader interpretive disagreements. Comparison of interpretations of time saving and conventional methods and also inter-observer variability was achieved using the Cohen kappa coefficient analysis. RESULTS: Interpretations rendered using the time-saving method showed near-perfect agreement with those based on the full dynamic imaging protocol (Cohen kappa coefficient = 0.92 for both readers). Furthermore, nuclear medicine physician readers agreed with each other (Cohen kappa coefficient = 0.95 between the 2 readers), indicating minimal inter observer variability using this novel optimized technique. CONCLUSION: In the setting of suspected acute cholecystitis, imaging resource utilization may be improved, via reduced gamma camera and technologist time, using a novel time saving method without sacrificing diagnostic accuracy. Multicenter larger trials, however, will be necessary to establish reproducibility. PMID- 27268321 TI - Electrophilic Aromatic Substitution: New Insights into an Old Class of Reactions. AB - The classic SEAr mechanism of electrophilic aromatic substitution (EAS) reactions described in textbooks, monographs, and reviews comprises the obligatory formation of arenium ion intermediates (sigma complexes) in a two-stage process. Our findings from several studies of EAS reactions challenge the generality of this mechanistic paradigm. This Account focuses on recent computational and experimental results for three types of EAS reactions: halogenation with molecular chlorine and bromine, nitration by mixed acid (mixture of nitric and sulfuric acids), and sulfonation with SO3. Our combined computational and experimental investigation of the chlorination of anisole with molecular chlorine in CCl4 found that addition-elimination pathways compete with the direct substitution processes. Detailed NMR investigation of the course of experimental anisole chlorination at varying temperatures revealed the formation of addition byproducts. Moreover, in the absence of Lewis acid catalysis, the direct halogenation processes do not involve arenium ion intermediates but instead proceed via concerted single transition states. We also obtained analogous results for the chlorination and bromination of several arenes in nonpolar solvents. We explored by theoretical computations and experimental spectroscopic studies the classic reaction of benzene nitration by mixed acid. The structure of the first intermediate in this process has been a subject of contradicting views. We have reported clear experimental UV/vis spectroscopic evidence for the formation of the first intermediate in this reaction. Our broader theoretical modeling of the process considers the effects of the medium as a bulk solvent but also the specific interactions of a H2SO4 solvent molecule with intermediates and transition states along the reaction path. In harmony with the obtained spectroscopic data, our computational results reveal that the structure of the initial pi complex precludes the possibility of electronic charge transfer from the benzene pi system to the nitronium unit. In contrast to usual interpretations, our computational results provide compelling evidence that in nonpolar, noncomplexing media and in the absence of catalysts, the mechanism of aromatic sulfonation with sulfur trioxide is concerted and does not involve the conventional sigma-complex (Wheland) intermediates. Stable under such conditions, (SO3)2 dimers react with benzene much more readily than monomeric sulfur trioxide. In polar (complexing) media, the reaction follows the classic two-stage SEAr mechanism. Still, the rate-controlling transition state involves two SO3 molecules. The reactivity and regioselectivity in EAS reactions that follow the classic mechanistic scheme are quantified using a theoretically evaluated quantity, the electrophile affinity (Ealpha), which measures the stabilization energy associated with the formation of arenium ions. Examples of applications are provided. PMID- 27268381 TI - Carbetocin versus syntometrine for prevention of postpartum hemorrhage after cesarean section. AB - OBJECTIVE: To compare effectiveness and tolerability of carbetocin versus syntometrine in prevention of postpartum hemorrhage (PPH) after cesarean section (CS). METHODS: A double-blind randomized study conducted on 300 pregnant subjected randomly either to single 100 MUg IV dose of carbetocin (150 women) or combination of 5 IU oxytocin and 0.2 mg ergometrine (150 women) after fetal extraction and before placental removal. Primary outcome parameter was the occurrence of PPH. Other parameters were hemoglobin and hematocrit changes, the need of additional oxytocic, hemodynamic changes and occurrence of side effects. RESULTS: There was no significant difference between the two study groups regarding hemoglobin and hematocrit at start of CS and after 2 days of surgery and mean blood loss during the operation (p > 0.05). There was a highly significant difference between the two study groups regarding incidence of primary PPH (2.7% versus10%) and the need of additional oxytocic (3.3% versus17.3%). Women in oxytocin group showed a statistically significant lower systolic and diastolic blood pressure at 1, 5 and 30 min than women in carbetocin group. Women in carbetocin group experienced more metallic taste, flushing, headache, dizziness, dyspnea and itching, while women in oxytocin methergine group experienced more palpitations. CONCLUSIONS: Carbetocin is a reasonable effective alternative to syntometrine in prevention of PPH after cesarean delivery. PMID- 27268382 TI - Palladium-Assisted Removal of a Solubilizing Tag from a Cys Side Chain To Facilitate Peptide and Protein Synthesis. AB - Reversible attachment of solubilizing tags to hydrophobic peptides to facilitate their purification and ligation is an essential yet challenging task in chemical protein synthesis. The efficient palladium-assisted removal of the solubilizing tag linked to the Cys side chain is reported. The strategy was applied for the efficient preparation of histone protein H4 from two fragments via one-pot operation of ligation, removal of the solubilizing tag, and desulfurization. PMID- 27268383 TI - The susceptibility of plasma coagulation factor XI to nitration and peroxynitrite action. AB - Coagulation factor XI is present in blood plasma as the zymogen, like other serine proteases of hemostatic system, but as the only coagulation factor forms 140-160kDa homodimers. Its activation is induced by thrombin, and a positive feedback increases the generation of the extra thrombin. Experimental and clinical observations confirm protective roles of factor XI deficiencies in certain types of thromboembolic disorders. Thromboembolism still causes serious problems for modern civilization. Diseases associated with the blood coagulation system are often associated with inflammation and oxidative stress. Peroxynitrite is produced from nitric oxide and superoxide in inflammatory diseases. The aim of the current study is to evaluate effects of nitrative stress triggered by peroxynitrite on coagulation factor XI in human plasma employing biochemical and bioinformatic methods. The amidolytic assay shows increase in factor XI activity triggered by peroxynitrite. Peroxynitrite interferes factor XI by nitration and fragmentation, which is demonstrated by immunoprecipitation followed by western blotting. Nitrated factor XI is even present in control blood plasma. The results suggest possible modifications of factor XI on the molecular level. Computer simulations show tyrosine residues as targets of peroxynitrite action. The modifications induced by peroxynitrite in factor XI might be important in thrombotic disorders. PMID- 27268384 TI - Thermal stability and binding energetics of thymidylate synthase ThyX. AB - The bacterial thymidylate synthase ThyX is a multisubstrate flavoenzyme that takes part in the de novo synthesis of thymidylate in a variety of microorganisms. Herein we study the effect of FAD and dUMP binding on the thermal stability of wild type (WT) ThyX from the mesophilic Paramecium bursaria chlorella virus-1 (PBCV-1) and from the thermophilic bacterium Thermotoga maritima (TmThyX), and from two variants of TmThyX, Y91F and S88W, using differential scanning calorimetry. The energetics underlying these processes was characterized by isothermal titration calorimetry. The PBCV-1 protein is significantly less stable against the thermal challenge than the TmThyX WT. FAD exerted stabilizing effect greater for PBCV-1 than for TmThyX and for both mutants, whereas binding of dUMP to FAD-loaded proteins stabilized further only TmThyX. Different thermodynamic signatures describe the FAD binding to the WT ThyX proteins. While TmThyX binds FAD with a low MUM binding affinity in a process characterized by a favorable entropy change, the assembly of PBCV-1 with FAD is governed by a large enthalpy change opposed by an unfavorable entropy change resulting in a relatively strong nM binding. An enthalpy-driven formation of a high affinity ternary ThyX/FAD/dUMP complex was observed only for TmThyX. PMID- 27268385 TI - Antioxidant and hepatoprotective properties of dried fig against oxidative stress and hepatotoxicity in rats. AB - The aim of this study was to investigate the hepatoprotective effect and antioxidant role of dried fig (DF) (Ficus carica L.) against ethanol-induced oxidative stress. Experiment was designed as normal Control, 20% ethanol, 10% DF and 10% DF+20% ethanol groups. The hepatoprotective and antioxidant role of the dried DF supplementation feed against ethanol induced oxidatif stress were evaluated by liver histopathological changes, measuring liver damage serum enzymes (LDSE), antioxidant defense system (ADS) and malondialdehyde (MDA) content in various tissues of rats following the exposure of experimental for 50days. The biochemical analysis showed a considerable increase the LDSE in the ethanol group as compared to that of control group whereas, decreased in 10% DF+20% ethanol group as compared to that of ethanol group. In addition, the DF supplementation diet restored the ethanol-induced MDA and ADS towards to control. The hepatoprotection of DF is further substantiated by the almost normal histologic findings of liver in 10% DF+20% ethanol group against degenerative changes in ethanol group. The results indicated that the DF could be as important as diet-derived antioxidants and antihepatotoxicity in preventing oxidative damage in the tissues by inhibiting the production of ethanol-induced free radicals and hepatotoxicity in rats. PMID- 27268386 TI - Predictors of Sexual Minority Youth's Reported Suicide Attempts and Mental Health. AB - Lesbian, gay, and bisexual youth (LGBY) report higher rates of mental health concerns compared to heterosexual youth due to minority stressors. This study examined the interpersonal and intrapersonal variables that predict psychological distress and self-reported suicide attempts in a sample of 61 LGBY in the Mid South, which is a highly overlooked regional area for LGBY research. Youth who lost friends when coming out were 29 times more likely to report suicide attempts, and those who experienced psychological maltreatment from caregivers were 9.5 times more likely to report a suicide attempt. Internalized heterosexism, feelings of guilt or shame, and psychological maltreatment from caregivers were significant predictors of depression and anxiety symptoms. This study highlights the importance of creating affirming spaces for LGBY, particularly in areas of the country that experience greater political oppression of sexual minorities, such as the Mid-South. PMID- 27268388 TI - Which Child Will Live or Die in France: Examining Physician Responsibility for Critically Ill Children. AB - There exists some controversy regarding the roles of parents and physicians for life-support decisions for critically ill children. French medical literature asserts that it is inappropriate for parents to bear such responsibilities. Physicians are commonly responsible for these decisions. The aims of this study were to (a) outline how life-support decisions are made for critically ill children in France; (b) examine the cultural context within which these decisional practices have arisen; and (c) analyse the ethical implications of these practices. Data were obtained in 2004 from consultations with relevant experts, relevant French medical guidelines, French print media, empirical research reports and related seminal publications. Specific themes that were identified included: (1) the physician is responsible for medical decision making for children; (2) French physicians caring for critically ill children bear a societal responsibility for preventing severely 'handicapped' survivors; (3) physician authority is rooted in State responsibility for children's welfare; and (4) active euthanasia is sometimes practised to prevent the creation of 'les handicapes'. These findings highlight ethical concerns that can result from assigning some physicians such largely unquestioned societal moral agency. PMID- 27268387 TI - Blu-ray Technology-Based Quantitative Assays for Cardiac Markers: From Disc Activation to Multiplex Detection. AB - Acute myocardial infarction (AMI) is the leading cause of mortality and morbidity globally. To reduce the number of mortalities, reliable and rapid point-of-care (POC) diagnosis of AMI is extremely critical. We herein present a Blu-ray technology-based assay platform for multiplex cardiac biomarker detection; not only off-the-shelf Blu-ray discs (BDs) were adapted as substrates to prepare standard immunoassays and DNA aptamer/antibody hybrid assays for the three key cardiac marker proteins (myoglobin, troponin I, and C-creative protein) but also an unmodified optical drive was directly employed to read the assay results digitally. In particular, we have shown that all three cardiac markers can be quantitated in their respective physiological ranges of interest, and the detection limits achieved are comparable with conventional enzyme-linked immunosorbent assay (ELISA) kits. The Blu-ray assay platform was further validated by measuring real-world samples and establishing a linear correlation with the simultaneously obtained ELISA data. Without the need to modify either the hardware (Blu-ray discs and optical drives) or the software driver, this assay-on-a-BD technique promises to be a low-cost user-friendly quantitative tool for on-site chemical analysis and POC medical diagnosis. PMID- 27268389 TI - Stigma, Gender, and their Impact on Patients with Tuberculosis in Rural Bangladesh. AB - In addition to marginalization by poverty and ethnicity, gender is likely to contribute to vulnerability to TB-related stigma affecting women. Stigma often contributes to psychosocial problems and emotional suffering, and it may hinder help seeking and treatment adherence. TB-related stigma and its gender-specific features have not been carefully studied in Bangladesh, and such research is needed to reduce adverse effects of stigma. This study assessed and compared stigma in women and men, and identified crosscutting and gender-specific features of TB-related stigma. To assess stigma and the context of TB-related illness experience, meaning and help seeking behavior from patients' perspectives, a cultural epidemiological study administered a locally adapted semi-structured EMIC interview to 50 women and 52 men with pulmonary TB in rural Bangladesh. Indicators of TB-related stigma were assessed individually and collectively in a validated index. They were compared by sex, and illness narratives elaborated features of stigma with reference to features of TB. The study showed that six indicators of TB-related stigma were more prominent in accounts of women and two were more prominent in men's interviews. Gender differences appeared somewhat less after adjusting for other sociodemographic variables, and age was most significantly inversely related to stigma. Features of stigma more prominent in the accounts of women included feeling shamed or embarrassed, thinking less of themselves and feeling that others refused to visit or avoided them. Men were less likely to disclose their condition to a confidant, stay away from work or report that their spouse refused sex because of TB. Effective public health information and counselling sensitive to gender-specific features of stigma are needed to protect TB patients from the adverse impact of avoidable stigma. Further research is needed to clarify effects of gender-specific features of felt and enacted stigma on help seeking and treatment adherence. PMID- 27268390 TI - Kal Dristi , Stolen Babies and 'Blocked Uteruses': Poverty and Infertility Anxieties among Married Adolescent Women Living in a Slum in Dhaka, Bangladesh. AB - The paper is about the neglect of infertility and women's interests in the health policy of developing countries, and how this shapes married adolescent women's understandings and practices surrounding infertility. Ethnographic fieldwork among married adolescent girls, aged 15-19, was carried out in a slum in Dhaka, Bangladesh from December 2001 to January 2003, including 50 in-depth interviews and eight case studies from 153 married adolescent girls, and observations and discussions with family and community members. There are newer understandings with the re-labelling of infertility from spirit world afflictions to something that is also attributed to family planning and 'build up of fat' in the uterus and stomach. Corrective practices range from not using or discontinuing a contraceptive method, dilatation and curettage (D&C) and visiting traditional healers. The absence of state services to address infertility concerns has implications for contraceptive use, with unintended pregnancies and unsafe abortions. Local beliefs continue to largely attribute the primary cause of infertility to the spirit world, but the emergence of newer infertility understandings reveal the influence of Western cultural beliefs (family planning campaigns, health practices influenced by biomedicine) and highlight the gender politics in the harsh environment of urban slums. PMID- 27268391 TI - Children, Pregnant Women and the Culture of Malaria in Two Rural Communities of Ghana. AB - The Malaria situation in Ghana is typical of many tropical African countries, where it remains a major cause of morbidity and mortality. Control methods generally emphasize prompt diagnosis and treatment. However, local experiences and meanings continue to influence help-seeking behaviour, which either promotes risk of infections or prevention. The aim of this study was to elicit relevant contemporary ethnographic features of malaria in children and pregnant women in two rural villages in Ghana for intervention. Ethnographic data collection methods such as free listing and rating, participatory mapping, focus group discussions and in-depth interviews were used. Malaria was listed as the most common illness in the study communities. Outside help is sought two to three days after illness onset. Mosquitoes were identified as a major nuisance and a cause of malaria and convulsions. This study highlights sociocultural features of malaria in two rural Ghanaian communities, and it indicates needs for regular re evaluation of community experiences, meanings and behaviour to inform the implementation and effectiveness of control programmes. PMID- 27268392 TI - 'Are We One Body?' Body Boundaries in Telesomatic Experiences. AB - This paper explores the embodiedness of body boundaries in the telesomatic experiences of 20 adult twins. Respondents were recruited through snowball sampling resulting in 16 in-depth face-to-face interviews. Interviews were analysed using an immersion-crystallization approach within a meaning-centred interpretive framework. Respondents often experienced trouble making subject object distinctions between themselves and their co-twins that often resulted in them posing the question, 'Are we (myself and my co-twin) one body?' Their experiences suggest that, sometimes symptoms of one illness are experienced as shared between two people, and their experiences highlight the ethical nature of individualism in western cultures as twins frequently do not view a greater level of attachment to their co-twins as pathological but as something special. We suggest that controversy regarding the ontological status of parapsychological phenomena has resulted in anthropologists being slow to consider these and similar experiences in western cultures as topics worthy of research. PMID- 27268393 TI - A Service Or a Right: Informed Consent for HIV-Positive Latin American Men in Japan. AB - Since April 1996, Japanese health care providers who practise informed consent have been financially rewarded. Although there is no precedent for this financial gain, there are no detailed studies. Focused on a group of Latin American men living with HIV/AIDS, this paper clarifies the actual practices of informed consent at Japanese medical facilities. Twenty HIV-positive men were interviewed in order to investigate how they obtained medical treatment and how they were informed about their physical condition. From April to September 2002 and during August 2003 and 2004, a set of six interviews were conducted with each male, who were 28-37 years old. Participants were acquired through a hospital and a non governmental organization, and by snowball sampling. The interviews showed that most of the informants received information concerning medical treatment, but they were advised neither about alternative treatments nor about the feasibility of seeking a third party's advice. Informed consent and communication between the informants and physicians were obstructed by language and structural, as well as cultural barriers. In conclusion, this paper adds a new dimension to the understanding of informed consent as the authors regard the practice as an educational process for health care providers and patients. PMID- 27268394 TI - The Voice of God. AB - Prayer and verbally answered prayer would seem to offer powerful evidence in relation to the question of human agency. Forty members of an English Pentecostal group completed a questionnaire on prayer: 25 reported an answering voice from God, 15 of them hearing Him aloud. The latter groups were interviewed and characteristics of phenomenology and context elicited. The voice of God cannot be held to be ipso facto pathological and many reported its utility in situations of doubt or difficulty. PMID- 27268397 TI - Insiders and Outsiders and Insider(s) Again in the (In)fertility World. PMID- 27268396 TI - The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection. AB - The aim of this study was to compare cytokine expression on both gene and protein levels in acute and chronic phase of HIV type 1 (HIV-1) infection. Thirty four patients were enrolled for cytokine expression analysis on protein level in acute and chronic stage of HIV-1 infection. Using PCR array technology, expression of 84 cytokine genes was measured in 3 patients in acute and 3 patients in chronic stage of HIV-1 infection. Bead-based cytometry was used to quantify levels of Th1/Th2/Th9/Th17/Th22 cytokines. The results showed statistically significant increase of 13 cytokine gene expression (cd40lg, csf2, ifna5, il12b, il1b, il20, lta, osm, spp1, tgfa, tnfsf 11, 14 and 8) and downregulation of the il12a expression in chronic HIV type 1 infection. Concentrations of IL-10, IL-4 and TNF alpha were increased in the acute HIV type 1 infection when compared to control group. During chronic HIV type 1 infection there was an increase of IL-10, TNF alpha, IL-2, IL-6, IL-13 and IL-22 levels when compared to control group. Comparison of cytokine expression between two stages of infection showed a significant decrease in IL-9 concentration. This study showed changes in cytokine profiles on both gene and protein levels in different stages of HIV-infection. PMID- 27268395 TI - Heads, stalks and everything else: how can antibodies eradicate influenza as a human disease? AB - Current seasonal influenza virus vaccines are effective against infection but they have to be reformulated on a regular basis to counter antigenic variations. The majority of the antibodies induced in response to seasonal vaccination are strain-specific. However, antibodies targeting conserved epitopes on the hemagglutinin protein have been identified and they offer broad protection. Most of these antibodies bind the hemagglutinin stalk domain and are generated from preexisting memory B cells. Broadly protective stalk-biased responses induced by antigenically divergent influenza strains, in concert with prior immunity, are sufficient to eradicate seasonally circulating strains. Future vaccine trials should aim to harness and maintain such a response with the realistic goal of developing a universal influenza vaccine. PMID- 27268398 TI - Slaughter of pregnant cattle in German abattoirs--current situation and prevalence: a cross-sectional study. AB - BACKGROUND: The slaughter of pregnant cattle and the fate of the foetuses are relatively new subjects in the field of animal welfare. The Scientific Committee on Veterinary Measures relating to Public Health (SCVPH), however, does not believe this topic to be a critical issue because of the hitherto supposed rare occurrence of this practice. Some previous studies though, contradict this assessment, emphasising its relevance to animal welfare. With regard to the heterogeneous study design of previous investigations, the objective of this study is to evaluate the current situation concerning the slaughter of pregnant cattle in different German abattoirs. Additionally, the prevalence was assessed semi-quantitatively on the basis of a cross-sectional, voluntary and anonymous survey that was conducted amongst senior veterinary students of the University of Leipzig from 2010 until 2013. RESULTS: Of 255 evaluable questionnaires, 157 (63.6%) mention the slaughter of pregnant cattle, corresponding to 76.9% of all visited abattoirs. Slaughter of pregnant cattle is reported often (>10% of females) in 6 (3.8%), frequently (1-10% of females) in 56 (35.7%), and rarely (<1% of females) in 95 (60.5%) of all cases (n = 157) respectively. About 50% of these animals were reported to be in the second or third stage of gestation. 15 (10.6%) of 142 questionnaires providing information about the foetus, state that the foetus showed visible vital signs after the death of the mother, but in one case the foetus was euthanized subsequently. CONCLUSIONS: The results show that the slaughter of pregnant cattle is a common and widespread practice in German abattoirs. The SCVPH's assumption that pregnant cattle are only slaughtered in rare exceptional cases can no longer be maintained. The high proportion of foetuses in the second and third gestational stage must also be considered. In this context the implementation of suitable studies and detailed analysis of the current situation is indispensable to ensure the high standards in animal welfare in Germany and Europe. PMID- 27268399 TI - DNA Replication in Engineered Escherichia coli Genomes with Extra Replication Origins. AB - The standard outline of bacterial genomes is a single circular chromosome with a single replication origin. From the bioengineering perspective, it appears attractive to extend this basic setup. Bacteria with split chromosomes or multiple replication origins have been successfully constructed in the last few years. The characteristics of these engineered strains will largely depend on the respective DNA replication patterns. However, the DNA replication has not been investigated systematically in engineered bacteria with multiple origins or split replicons. Here we fill this gap by studying a set of strains consisting of (i) E. coli strains with an extra copy of the native replication origin (oriC), (ii) E. coli strains with an extra copy of the replication origin from the secondary chromosome of Vibrio cholerae (oriII), and (iii) a strain in which the E. coli chromosome is split into two linear replicons. A combination of flow cytometry, microarray-based comparative genomic hybridization (CGH), and modeling revealed silencing of extra oriC copies and differential timing of ectopic oriII copies compared to the native oriC. The results were used to derive construction rules for future multiorigin and multireplicon projects. PMID- 27268400 TI - Diagnosing cystic fibrosis-related diabetes: current methods and challenges. AB - INTRODUCTION: Cystic fibrosis-related diabetes (CFRD) is the end-point of a spectrum of glucose abnormalities in cystic fibrosis that begins with early insulin deficiency and ultimately results in accelerated nutritional decline and loss of lung function. Current diagnostic and management regimens are unable to entirely reverse this clinical decline. AREAS COVERED: This review summarises the current understanding of the pathophysiology of CFRD, the issues associated with using oral glucose tolerance tests in CF and the challenges faced in making the diagnosis of CFRD. Medline database searches were conducted using search terms "Cystic Fibrosis Related Diabetes", "Cystic Fibrosis" AND "glucose", "Cystic Fibrosis" AND "insulin", "Cystic Fibrosis" AND "Diabetes". Additionally, reference lists were studied. Expert commentary: Increasing evidence points to early glucose abnormalities being clinically relevant in cystic fibrosis and as such novel diagnostic methods such as continuous glucose monitoring or 30 minute sampled oral glucose tolerance test (OGTT) may play a key role in the future in the screening and diagnosis of early glucose abnormalities in CF. PMID- 27268401 TI - An empirical investigation of incompleteness in a large clinical sample of obsessive compulsive disorder. AB - Obsessive Compulsive Disorder (OCD) is a disorder with heterogeneous clinical presentations. To advance our understanding of this heterogeneity we investigated the prevalence and clinical features associated with incompleteness (INC), a putative underlying core feature of OCD. We predicted INC would be prominent in individuals with OCD and associated with greater severity and impairment. We examined the impact of INC in 307 adults with primary OCD. Participants with clinically significant INC (22.8% of the sample) had significantly greater OCD severity, greater rates of comorbidity, poorer ratings of functioning, lower quality of life, and higher rates of unemployment and disability. Participants with clinically significant INC were also more likely to be diagnosed with OCPD and to endorse symmetry/exactness obsessions and ordering/arranging compulsions than those who reported low INC. Our findings provide evidence that INC is associated with greater severity, comorbidity, and impairment, highlighting the need for improved assessment and treatment of INC in OCD. PMID- 27268402 TI - In Situ Analysis of the Growth and Dielectric Properties of Organic Self Assembled Monolayers: A Way To Tailor Organic Layers for Electronic Applications. AB - Organic nanoscale science and technology relies on the control of phenomena occurring at the molecular level. This is of particular importance for the self assembly of molecular monolayers (SAM) that can be used in various applications ranging from organic electronics to bioelectronic applications. However, the understanding of the elementary nanoscopic processes in molecular film growth is still in its infancy. Here, we developed a novel in situ and extremely sensitive detection method for the analysis of the electronic properties of molecular layer during molecular layer deposition. This low-frequency sensor (1 kHz) is employed to analyze the standard vapor deposition process of SAMs of molecules and, subsequently, it is used to optimize the growth process itself. By combining this method with an ex situ determination of the effective thickness of the resulting layers via ellipsometry, we observe a large difference of the permittivity (1 kHz) of the examined aminosilanes in the liquid state (epsilonliquid = 5.5-8.8) and in SAMs (epsilonSAM = 22-52, electric field in the plane of the layer). We ascribe this difference to either the different orientation and order of the molecules, the different density of molecules, or a combination of both effects. Our novel in situ analyses not only allows monitoring and optimizing the deposition of organic layers but also demonstrates the high potential of organic SAMs as organic high-k layers in electronic devices. PMID- 27268403 TI - Epstein-Barr virus infection is associated to patients with multiple myeloma and monoclonal gammopathy of undetermined significance. PMID- 27268405 TI - Intergenerational variation in sexual health attitudes and beliefs among Sudanese refugee communities in Australia. AB - The aim of this study was to develop intergenerational understanding of the factors perceived to be influencing the sexual health and wellbeing of young Sudanese refugees in Queensland, Australia. Data from 11 semi-structured, face-to face interviews exploring sexual health knowledge, attitudes and behaviours with young people aged 16 to 24 years, and five focus groups with adults from the broader Queensland Sudanese community, were compared and contrasted. Findings indicate that sexual health-related knowledge, attitudes and beliefs, along with patterns of sexual behaviour, are changing post-resettlement and this creates considerable intergenerational discord and family conflict. Study findings provide an understanding of how the interplay between traditional cultural gender, parenting and relationship norms and perceived normative Australian beliefs and patterns of behaviour influence the construction of both young people's and their parents' attitudes to sexual health post-arrival. We suggest that sexuality education programmes adapted to the specific cultural- and age related contexts need to be introduced early within the resettlement process for both young people and their families. PMID- 27268404 TI - Evaluation of Xpert(r) MTB/RIF and Ustar EasyNATTM TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania: a prospective descriptive study. AB - BACKGROUND: Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB endemic setting in Tanzania. METHODS: Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis. RESULTS: Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %. CONCLUSIONS: Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children. PMID- 27268406 TI - A framework for assessing outcomes from newborn screening: on the road to measuring its promise. AB - Newborn screening (NBS) is intended to identify congenital conditions prior to the onset of symptoms in order to provide early intervention that leads to improved outcomes. NBS is a public health success, providing reduction in mortality and improved developmental outcomes for screened conditions. However, it is less clear to what extent newborn screening achieves the long-term goals relating to improved health, growth, development and function. We propose a framework for assessing outcomes for the health and well-being of children identified through NBS programs. The framework proposed here, and this manuscript, were approved for publication by the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC). This framework can be applied to each screened condition within the Recommended Uniform Screening Panel (RUSP), recognizing that the data elements and measures will vary by condition. As an example, we applied the framework to sickle cell disease and phenylketonuria (PKU), two diverse conditions with different outcome measures and potential sources of data. Widespread and consistent application of this framework across state NBS and child health systems is envisioned as useful to standardize approaches to assessment of outcomes and for continuous improvement of the NBS and child health systems. SIGNIFICANCE: Successful interventions for newborn screening conditions have been a driving force for public health newborn screening for over fifty years. Organizing interventions and outcome measures into a standard framework to systematically assess outcomes has not yet come into practice. This paper presents a customizable outcomes framework for organizing measures for newborn screening condition-specific health outcomes, and an approach to identifying sources and challenges to populating those measures. PMID- 27268407 TI - Tracking medical genetic literature through machine learning. AB - There has been remarkable progress in identifying the causes of genetic conditions as well as understanding how changes in specific genes cause disease. Though difficult (and often superficial) to parse, an interesting tension involves emphasis on basic research aimed to dissect normal and abnormal biology versus more clearly clinical and therapeutic investigations. To examine one facet of this question and to better understand progress in Mendelian-related research, we developed an algorithm that classifies medical literature into three categories (Basic, Clinical, and Management) and conducted a retrospective analysis. We built a supervised machine learning classification model using the Azure Machine Learning (ML) Platform and analyzed the literature (1970-2014) from NCBI's Entrez Gene2Pubmed Database (http://www.ncbi.nlm.nih.gov/gene) using genes from the NHGRI's Clinical Genomics Database (http://research.nhgri.nih.gov/CGD/). We applied our model to 376,738 articles: 288,639 (76.6%) were classified as Basic, 54,178 (14.4%) as Clinical, and 24,569 (6.5%) as Management. The average classification accuracy was 92.2%. The rate of Clinical publication was significantly higher than Basic or Management. The rate of publication of article types differed significantly when divided into key eras: Human Genome Project (HGP) planning phase (1984-1990); HGP launch (1990) to publication (2001); following HGP completion to the "Next Generation" advent (2009); the era following 2009. In conclusion, in addition to the findings regarding the pace and focus of genetic progress, our algorithm produced a database that can be used in a variety of contexts including automating the identification of management related literature. PMID- 27268408 TI - Diversity and host specificity of coccidia (Apicomplexa: Eimeriidae) in native and introduced squirrel species. AB - Introduction of alien species into new areas can have detrimental effects on native ecosystems and impact the native species. The present study aims to identify coccidia infecting native and introduced squirrels in Italy, to gain insight into possible transmission patterns and role of monoxenous coccidia in mediating the competition between alien and native hosts. We collected 540 faecal samples of native red squirrels, Sciurus vulgaris, invasive alien grey squirrels, S. carolinensis, and introduced Pallas's squirrels, Callosciurus erythraeus. Total prevalence of Eimeria spp. was 95.6% in S. vulgaris, 95.7% in S. carolinensis and only 4.1% in C. erythraeus. Morphological examination revealed 3 Eimeria morphotypes. Phylogenetic analyses of Eimeria DNA based on 18S, ITS, cox I markers displayed fairly distinct monophyletic clades in the microscopically indistinguishable E2 morphotype, proving indisputable distinction between the isolates from red and grey squirrels. Grey squirrels successfully introduced E. lancasterensis from their native range, but this species does not spill over to native red squirrels. Similarly, there is no evidence for the transmission of E. sciurorum from red to grey squirrels. The possible transmission and the potential role of monoxenous coccidia in mediating the competition between native and invasive squirrels in Italy were not confirmed. PMID- 27268409 TI - National clinical coding of trans-sphenoidal pituitary surgery. PMID- 27268411 TI - A Nanoprinted Model of Interstitial Cancer Migration Reveals a Link between Cell Deformability and Proliferation. AB - Metastatic progression of tumors requires the coordinated dissemination of cancerous cells through interstitial tissues and their replication in distant body locations. Despite their importance in cancer treatment decisions, key factors, such as cell shape adaptation and the role it plays in dense tissue invasion by cancerous cells, are not well understood. Here, we employ a 3D electrohydrodynamic nanoprinting technology to generate vertical arrays of topographical pores that mimic interstitial tissue resistance to the mesenchymal migration of cancerous cells, in order to determine the effect of nuclear size, cell deformability, and cell-to-substrate adhesion on tissue invasion efficiency. The high spatial and temporal resolution of our analysis demonstrates that the ability of cells to deform depends on the cell cycle phase, peaks immediately after mitosis, and is key to the invasion process. Increased pore penetration efficiency by cells in early G1 phase also coincided with their lower nuclear volume and higher cell deformability, compared with the later cell cycle stages. Furthermore, artificial decondensation of chromatin induced an increase in cell and nuclear deformability and improved pore penetration efficiency of cells in G1. Together, these results underline that along the cell cycle cells have different abilities to dynamically remodel their actin cytoskeleton and induce nuclear shape changes, which determines their pore penetration efficiency. Thus, our results support a mechanism in which cell proliferation and pore penetration are functionally linked to favor the interstitial dissemination of metastatic cells. PMID- 27268410 TI - Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence. AB - STUDY QUESTION: Can RNA sequencing of human cumulus cells (CC) reveal molecular pathways involved in the physiology of reproductive aging? STUDY FINDING: Senescent but not young CC activate gene pathways associated with hypoxia and oxidative stress. WHAT IS KNOWN ALREADY: Shifts in socioeconomic norms are resulting in larger numbers of women postponing childbearing. The reproductive potential is sharply decreased with aging, and the reasons are poorly understood. Since CCs play an integral role in oocyte maturation and direct access to human oocytes is limited, we used whole transcriptome analysis of these somatic cells to gain insights into the molecular mechanisms playing a role in follicular senescence. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Twenty CC samples (from a total of 15 patients) were obtained from oocytes of either male factor or egg donor patients. RNA sequencing and bioinformatic tools were used to identify differentially expressed genes between CCs from seven aged and eight young patients (<35 (years old) y.o. vs >40 y.o.). Quantitative-PCR and immunoflourescent staining were used for validation. MAIN RESULTS AND THE ROLE OF CHANCE: RNA sequencing identified 11 572 genes expressed in CC of both age cohorts, 45 of which were differentially expressed. In CC collected from patients >40 y.o., genes involved in the hypoxia stress response (NOS2, RORA and NR4A3), vasculature development (NR2F2, PTHLH), glycolysis (RALGAPA2 and TBC1D4) and cAMP turnover (PDE4D) were significantly overexpressed when compared with CC of patients younger than 35 y.o. LIMITATIONS, REASONS FOR CAUTION: This study focused almost exclusively on assessing the genetic differences in CC transcriptome between young and older women. These genetic findings were not fully correlated with embryonic development and clinical outcome. WIDER IMPLICATIONS OF THE FINDINGS: Our data provide a new hypothesis-follicular hypoxia-as the main mechanism leading to ovarian follicular senescence and suggest a link between cumulus cell aging and oocyte quality decay. If specific molecular findings of hypoxia would be confirmed also in oocytes, genetic platforms could screen CC for hypoxic damage and identify healthier oocytes. Protocols of ovarian stimulation in older patients could also be adjusted to diminish oocyte exposure time to hypoxic follicles. LARGE SCALE DATA: GEO accession number: GSE81579 STUDY FUNDING AND COMPETING INTERESTS: Funded in part by EMD Serono Grant for Fertility Innovation (GFI). PMID- 27268412 TI - Expression and localization of X11 family proteins in neurons. AB - The X11/Mint family of proteins comprises X11/X11alpha/Mint1, X11L/X11beta/Mint2, and X11L2/X11gamma/Mint3. Each of these molecules is an adaptor protein that contains a phosphotyrosine interaction/binding (PI/PTB) and two PDZ domains in its carboxy-terminal region. X11/Mint family members associate with a broad spectrum of membrane proteins, including Alzheimer's beta-amyloid precursor protein (APP), alcadeins, and low density lipoprotein receptor proteins, as well as various cytoplasmic proteins including Arf, kalirin-7, and Munc18. In particular, X11 and X11L are thought to play various roles in the regulation of neural functions in brain. Nevertheless, the protein levels and respective localization of individual family members remain controversial. We analyzed the protein levels of X11 and X11L in the corresponding single- and double-knockout mice. X11 and X11L did not exhibit obvious changes of their protein levels when the other was absent, especially in cerebrum in which they were widely co expressed. In cerebellum, X11 and X11L localized in characteristic patterns in various types of neurons, and X11 protein level increased without an obvious ectopic localization in X11L-knockout mice. Interestingly, only X11L protein existed specifically in brain, whereas, contrary to the accepted view, X11 protein was detected at the highest levels in brain but was also strongly detected in pancreas, testis, and paranephros. Together, our results indicate that both X11 and X11L exert largely in brain neurons, but X11 may also function in peripheral tissues. PMID- 27268414 TI - The accuracy of blood pressure measured by arterial line and non-invasive cuff in critically ill children. AB - BACKGROUND: The accuracy of arterial lines (AL) using the flush test or stopcock test has not been described in children, nor has the difference between invasive arterial blood pressure (IABP) versus non-invasive cuff (NIBP) blood pressure. METHODS: After ethics approval and consent, we performed the flush test and stopcock test on AL (to determine over damping, under damping, and optimal damping), and determined the difference (NIBP-IABP) in systolic, diastolic, and mean blood pressure (DeltaSBP, DeltaDBP, and DeltaMAP). The primary outcome was incidence (95 % CI) of optimally damped AL. Predictors of DeltaBP (effect size (95 % CI)) were determined using multiple linear regression. RESULTS: There were 147 AL tests in 100 enrolled patients with mean age 44.7 (SD 56) months, weight 16.8 (SD 18.3) kg, male 59 %, postoperative-cardiovascular 52 %, peripheral-AL 78 %, inotropes 29 %, vasodilators 15 %, and ventilated 73 %. The flush test performed in 66 patients (45 %) showed optimal damping in 30 (46 %; 95 % CI 34, 57 %), over damping in 25 (38 %) and under damping in 11 patients (17 %). The stopcock test was over-damped in 128/146 patients (88 %), with the same damping as the flush test in 24/64 (38 %). In optimally damped (flush test) AL, DeltaSBP, DeltaDBP, and DeltaMAP were 0.8 (SD 12.2), -5.2 (SD 8.7), and -4.9 (7.6) respectively. A second set of AL tests was done 2 h later on the same day in 62 patients; AL damping often changed (10/28 flush tests) and DeltaBPs correlated poorly (r = 0.31-0.55). Predictors (effect size) of DeltaDBP were vasodilator infusion (15.6 (2.9 to 28.3); p = 0.016) and optimal damping (-7.2 (-12.2 to 2.2); p = 0.005); and of DeltaMAP were vasodilator infusion (10.0 (-0.3 to 20.4); p = 0.057) and optimal damping (-4.0 (-8 to 0.1); p = 0.058). There were no independent predictors of damping category (n = 66 flush tests). CONCLUSIONS: Optimally damped AL occur in half of critically ill children, and this is not predictable. There is much variability in ?BP between NIBP and the gold standard IABP, and this varies even in the same patient on the same day, and is not easily predictable. In critically ill children, NIBP may not be accurate enough to guide management, and more attention to ensuring the AL is optimally damped is needed. PMID- 27268413 TI - Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells. AB - Melatonin is a neurohormone and has high potent of antioxidant that is widely reported to be active against methamphetamine (METH)-induced toxicity to neuron, glial cells, and brain endothelial cells. However, the role of melatonin on the inflammatory responses which are mostly caused by blood-brain barrier (BBB) impairment by METH administration has not been investigated. This study used the primary rat brain microvascular endothelial cells (BMVECs) to determine the protective mechanism of melatonin on METH-induced inflammatory responses in the BBB via nuclear factor-KB (NF-kappaB) and nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Herein, we demonstrated that melatonin reduced the level of the inflammatory mediators, including intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, matrix metallopeptidase (MMP)-9, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) caused by METH. These responses were related to the decrease of the expression and translocation of the NF-kappaB p65 subunit and the activity of NADPH oxidase (NOX)-2. In addition, melatonin promoted the antioxidant processes, modulated the expression and translocation of Nrf2, and also increased the level of heme oxygenase (HO)-1, NAD (P) H: quinone oxidoreductase (NQO)-1, gamma glutamylcysteine synthase (gamma-GCLC), and the activity of superoxide dismutase (SOD) through NOX2 mechanism. In addition, we found that the protective role of melatonin in METH-induced inflammatory responses in the BBB was mediated through melatonin receptors (MT1/2). We concluded that the interaction of melatonin with its receptor prevented METH-induced inflammatory responses by suppressing the NF kappaB signaling and promoting the Nrf2 signaling before BBB impairment. PMID- 27268416 TI - Managing menstruation in the workplace: an overlooked issue in low- and middle income countries. AB - The potential menstrual hygiene management barriers faced by adolescent girls and women in workplace environments in low- and middle-income countries has been under addressed in research, programming and policy. Despite global efforts to reduce poverty among women in such contexts, there has been insufficient attention to the water and sanitation related barriers, specifically in relation to managing monthly menstruation, that may hinder girls' and women's contributions to the workplace, and their health and wellbeing. There is an urgent need to document the specific social and environmental barriers they may be facing in relation to menstrual management, to conduct a costing of the implications of inadequate supportive workplace environments for menstrual hygiene management, and to understand the implications for girls' and women's health and wellbeing. This will provide essential evidence for guiding national policy makers, the private sector, donors and activists focused on advancing girls' and women's rights. PMID- 27268415 TI - Efficacy of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline in Twin Families (VIPP-Twins): Study protocol for a randomized controlled trial. AB - BACKGROUND: Intervention programs with the aim of enhancing parenting quality have been found to be differentially effective in decreasing negative child outcomes such as externalizing behavioral problems, resulting in modest overall effect sizes. Here we present the protocol for a randomized controlled trial to examine the efficacy of the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline for Twin Families (VIPP-Twins) on parenting quality and children's behavioral control and social competence. In addition, we aim to test the differential susceptibility theory; we examine differential efficacy of the intervention based on genetic make-up or temperament for both parents and children. Lastly, we explore neurobiological mechanisms underlying intervention effects on children's developmental outcomes. METHODS/DESIGN: The original VIPP-SD was adapted for use in families with twins. The VIPP-Twins consists of five biweekly sessions in which the families are visited at home, parent-child interactions are videotaped and parents receive positive feedback on selected video fragments. Families (N = 225) with a same sex twin (mean age = 3.6 years) were recruited to participate in the study. The study consists of four assessments. After two baseline assessments in year 1 and year 2, a random 40 % of the sample will receive the VIPP-Twins program. The first post-test assessment will be carried out one month after the intervention and there will be a long term follow-up assessment two years after the intervention. Measures include observational assessments of parenting and children's social competence and behavioral control, and neurobiological assessments (i.e., hormonal functioning and neural (re-)activity). DISCUSSION: Results of the study will provide insights in the efficacy of the VIPP-Twins and reveal moderators and mediators of program efficacy. Overall the randomized controlled trial is an experimental test of the differential susceptibility theory. TRIAL REGISTRATION: Dutch Trial Register: NTR5312 ; Date registered: July 20, 2015. PMID- 27268417 TI - Comparison of panoramic radiography and CBCT to identify maxillary posterior roots invading the maxillary sinus. AB - OBJECTIVES: Given the limitations of panoramic radiography for assessing topographic relationship of maxillary teeth with sinus floor, the purpose of this study was to assess signs on panoramic radiography that could predict root protrusion into the sinus. METHODS: A total of 46 individuals (330 maxillary posterior teeth) who underwent panoramic radiography and CBCT were enrolled. The relationship between the posterior teeth and the maxillary sinus and panoramic radiography signs (projection of the root apices, interruption of the maxillary sinus floor, lamina dura, darkening in the root apices, and superiorly curving sinus floor enveloping the associated tooth root) associated with protrusion of root apices into the sinus were evaluated. RESULTS: There were differences between the imaging modalities about the positioning of the root apices regarding the sinus (p < 0.05). Only the projecting of the root apices and the interruption of the sinus floor on panoramic radiography were predictors for the root protrusion (p < 0.05). No significant association was observed for the other panoramic radiography signs (p > 0.05). CONCLUSIONS: The root projection into the sinus and the interruption of the sinus floor are indicative signs of root protrusion into the sinus on CBCT. PMID- 27268419 TI - The mediating role of general self-efficacy in the association between perceived social support and oral health-related quality of life after initial periodontal therapy. AB - BACKGROUND: Although initial periodontal therapy can ease some physical and psychological discomforts from periodontitis and improve patients' oral health related quality of life (OHRQoL), it is also vital to find positive resources from psychological and social aspects to promote the overall OHRQoL. This study aims to explore the associations of perceived social support (PSS) and general self-efficacy with OHRQoL and the mediating role of general self-efficacy in PSS OHRQoL association after initial periodontal therapy. METHODS: A prospective case series study was conducted among consecutive outpatients with chronic periodontitis during the period of July 2014-April 2015. A total of 145 eligible patients responded to OHRQoL questionnaire and periodontal examination at baseline. About 4 to 5 weeks after initial periodontal therapy, 120 patients completed the second OHRQoL measurement and periodontal examination, along with PSS and general self-efficacy measurement. The Wilcoxon matched-pairs signed-rank test was used to determine the difference between baseline and post-treatment OHRQoL scores and periodontal parameters. Hierarchical linear regression analysis was used to explore the associations of PSS and general self-efficacy with post treatment OHRQoL after adjusting for some demographic and periodontal variables. Asymptotic and resampling strategies were performed to explore the mediating role of general self-efficacy. RESULTS: Initial periodontal therapy resulted in a significant improvement in the mean total score and all domains of OHRQoL and all periodontal parameters measured. In hierarchical linear regression analysis, clinical attachment loss (CAL) was significantly and positively associated with post-treatment OHRQoL score (beta = 0.265, p < 0.01), while PSS (beta = -0.303, p < 0.01) and general self-efficacy (beta = -0.221, p < 0.01) were significantly and negatively associated with post-treatment OHRQL score, respectively. A significant mediating role of general self-efficacy (a*b = -0.139, BCa 95 % CI: 0.298, -0.011) in the association between PSS and post-treatment OHRQoL was revealed, and the proportion of the mediating role of general self-efficacy was 31.4 %. CONCLUSIONS: Initial periodontal therapy could significantly improve all aspects of OHRQoL. PSS and general self-efficacy could be the positive resources for improving OHRQoL after initial periodontal therapy among patients with periodontitis. General self-efficacy partly mediated the association between PSS and post-treatment OHRQoL. PMID- 27268420 TI - Heart failure in elderly patients, a global perspective. PMID- 27268418 TI - Transcriptomic comparison of Drosophila snRNP biogenesis mutants reveals mutant specific changes in pre-mRNA processing: implications for spinal muscular atrophy. AB - Survival motor neuron (SMN) functions in the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs) that catalyze pre-mRNA splicing. Here, we used disruptions in Smn and two additional snRNP biogenesis genes, Phax and Ars2, to classify RNA processing differences as snRNP-dependent or gene-specific in Drosophila Phax and Smn mutants exhibited comparable reductions in snRNAs, and comparison of their transcriptomes uncovered shared sets of RNA processing changes. In contrast, Ars2 mutants displayed only small decreases in snRNA levels, and RNA processing changes in these mutants were generally distinct from those identified in Phax and Smn animals. Instead, RNA processing changes in Ars2 mutants support the known interaction of Ars2 protein with the cap-binding complex, as splicing changes showed a clear bias toward the first intron. Bypassing disruptions in snRNP biogenesis, direct knockdown of spliceosomal proteins caused similar changes in the splicing of snRNP-dependent events. However, these snRNP-dependent events were largely unaltered in three Smn mutants expressing missense mutations that were originally identified in human spinal muscular atrophy (SMA) patients. Hence, findings here clarify the contributions of Phax, Smn, and Ars2 to snRNP biogenesis in Drosophila, and loss-of-function mutants for these proteins reveal differences that help disentangle cause and effect in SMA model flies. PMID- 27268421 TI - Dupilumab therapy provides clinically meaningful improvement in patient-reported outcomes (PROs): A phase IIb, randomized, placebo-controlled, clinical trial in adult patients with moderate to severe atopic dermatitis (AD). AB - BACKGROUND: Moderate to severe atopic dermatitis (AD) is associated with substantial patient burden despite current therapies. OBJECTIVE: We sought to evaluate dupilumab treatment on patient-reported outcomes in adults with moderate to severe AD. METHODS: Adults (N = 380) with moderate to severe AD inadequately controlled by topical medications were randomized to 16 weeks of double-blind, subcutaneous treatment with dupilumab 100 mg every 4 weeks, 200 mg every 2 weeks, 300 mg every 2 weeks, 300 mg once weekly, or placebo. Patient-reported outcomes included pruritus numeric rating scale; patient-reported sleep item on Scoring AD scale; Patient-Oriented Eczema Measure; Hospital Anxiety and Depression Scale; Dermatology Life Quality Index; and 5-dimension 3-level EuroQol. RESULTS: Dupilumab reduced peak itch at 16 weeks relative to placebo by 1.1 to 3.2 points on numeric rating scale (P < .0001 all doses, except 100 mg every 4 weeks P < .05); improved sleep and health-related quality of life on Dermatology Life Quality Index and 5-dimension 3-level EuroQol (P < .05 all doses, except 100 mg every 4 weeks); and reduced anxiety and depression symptoms (P < .05 all doses). Dupilumab's effects appeared early and achieved clinically relevant improvements without significant safety concerns. LIMITATIONS: There are potential cultural differences affecting patient-reported outcome responses. Outcomes were secondary or exploratory end points. CONCLUSION: Dupilumab produced early and sustained patient-reported and clinically relevant improvements in sleep, mental health, and health-related quality of life; the two 300-mg dose regimens resulted in greatest benefits. PMID- 27268423 TI - Surface Nanobubbles Studied by Time-Resolved Fluorescence Microscopy Methods Combined with AFM: The Impact of Surface Treatment on Nanobubble Nucleation. AB - The impact of surface treatment and modification on surface nanobubble nucleation in water has been addressed by a new combination of fluorescence lifetime imaging microscopy (FLIM) and atomic force microscopy (AFM). In this study, rhodamine 6G (Rh6G)-labeled surface nanobubbles nucleated by the ethanol-water exchange were studied on differently cleaned borosilicate glass, silanized glass as well as self-assembled monolayers on transparent gold by combined AFM-FLIM. While the AFM data confirmed earlier reports on surface nanobubble nucleation, size, and apparent contact angles in dependence of the underlying substrate, the colocalization of these elevated features with highly fluorescent features observed in confocal intensity images added new information. By analyzing the characteristic contributions to the excited state lifetime of Rh6G in decay curves obtained from time-correlated single photon counting (TCSPC) experiments, the characteristic short-lived (<600 ps) component of could be associated with an emission at the gas-water interface. Its colocalization with nanobubble-like features in the AFM height images provides evidence for the observation of gas filled surface nanobubbles. While piranha-cleaned glass supported nanobubbles, milder UV-ozone or oxygen plasma treatment afforded glass-water interfaces, where no nanobubbles were observed by combined AFM-FLIM. Finally, the number density of nanobubbles scaled inversely with increasing surface hydrophobicity. PMID- 27268425 TI - New authority to oversee NHS complaints system must be independent, say MPs. PMID- 27268424 TI - Assessing cortical synchronization during transcranial direct current stimulation: A graph-theoretical analysis. AB - Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cortical excitability and modulate behaviour in a polarity dependent way. Despite the widespread use of this method in the neuroscience field, its effects on ongoing local or global (network level) neuronal activity are still not foreseeable. A way to shed light on the neuronal mechanisms underlying the cortical connectivity changes induced by tDCS is provided by the combination of tDCS with electroencephalography (EEG). In this study, twelve healthy subjects underwent online tDCS-EEG recording (i.e., simultaneous), during resting-state, using 19 EEG channels. The protocol involved anodal, cathodal and sham stimulation conditions, with the active and the reference electrodes in the left frontocentral area (FC3) and on the forehead over the right eyebrow, respectively. The data were processed using a network model, based on graph theory and the synchronization likelihood. The resulting graphs were analysed for four frequency bands (theta, alpha, beta and gamma) to evaluate the presence of tDCS-induced differences in synchronization patterns and graph theory measures. The resting state network connectivity resulted altered during tDCS, in a polarity-specific manner for theta and alpha bands. Anodal tDCS weakened synchronization with respect to the baseline over the fronto-central areas in the left hemisphere, for theta band (p<0.05). In contrast, during cathodal tDCS a significant increase in inter-hemispheric synchronization connectivity was observed over the centro-parietal, centro-occipital and parieto-occipital areas for the alpha band (p<0.05). Local graph measures showed a tDCS-induced polarity specific differences that regarded modifications of network activities rather than specific region properties. Our results show that applying tDCS during the resting state modulates local synchronization as well as network properties in slow frequency bands, in a polarity-specific manner. PMID- 27268422 TI - Respiratory and Bronchitic Symptoms Predict Intention to Quit Smoking among Current Smokers with, and at Risk for, Chronic Obstructive Pulmonary Disease. AB - RATIONALE: Smoking cessation is the most important intervention for patients with chronic obstructive pulmonary disease (COPD). What leads smokers with COPD to quit smoking remains unknown. OBJECTIVES: We sought to examine the association between respiratory symptoms and other markers of COPD severity with intention to quit smoking among a cohort of patients with probable COPD. METHODS: We conducted a cross-sectional study of subjects with COPD or fixed airflow obstruction clinically diagnosed on the basis of pulmonary function testing. The subjects were identified in the COPD Outcomes-based Network for Clinical Effectiveness and Research Translation multicenter registry. The primary outcome was the intention to quit smoking within the next 30 days (yes or no), which was examined using model building with multivariable logistic regression, clustered by study site. MEASUREMENTS AND MAIN RESULTS: We identified 338 current smokers with COPD via the registry. Of these subjects, 57.4% (n = 194) had confirmed airflow obstruction based on pulmonary function testing. Nearly one-third (29.2%; n = 99) intended to quit smoking in the next 30 days. In adjusted analyses, compared with subjects without airflow obstruction based on pulmonary function testing, subjects with Global Initiative for Chronic Obstructive Lung Disease stage I/II COPD were more likely to be motivated to quit (odds ratio [OR], 1.85; 95% confidence interval [CI], 1.37-2.49), with no association found for subjects with Global Initiative for Chronic Obstructive Lung Disease stage III/IV disease. Among the entire cohort, frequent phlegm (OR, 2.10; 95% CI, 1.22-3.64), cough (OR, 1.74; 95% CI, 1.01-2.99), wheeze (OR, 1.73; 95% CI, 1.09-3.18), and higher modified Medical Research Council dyspnea score (OR, 1.26 per point; 95% CI, 1.13 1.41) were associated with increased odds of intending to quit smoking. Low self reported health was associated with decreased odds of intending to quit (OR, 0.75; 95% CI, 0.62-0.92). CONCLUSIONS: Frequent cough, phlegm, wheeze, and shortness of breath were associated with intention to quit smoking in the next 30 days, with a less clear relationship for severity of illness graded by pulmonary function testing and self-rated health. These findings can be used to inform the content of tobacco cessation interventions to provide a more tailored approach for patients with respiratory diseases such as COPD. PMID- 27268426 TI - Langmuir-Blodgett Films of the Metal-Organic Framework MIL-101(Cr): Preparation, Characterization, and CO2 Adsorption Study Using a QCM-Based Setup. AB - This work reports the fabrication and characterization of Langmuir-Blodgett films of nanoparticles (size 51 +/- 10 nm) of the metal organic framework MIL-101(Cr). LB film characterization by SEM, UV-vis, GIXRD, and QCM has shown that the addition of 1 wt % of behenic acid to MOF dispersion allows obtaining dense monolayers at the air-water interface that can be deposited onto solid substrates of different nature with transfer ratios close to 1. Moreover, a QCM-based setup has been built and used for the first time to measure CO2 adsorption isotherms at 303 K on MOF LB films, proving that LB films with MOF masses between 1.2 (1 layer) and 2.3 (2 layers) MUg can be used to obtain accurate adsorption values at 100 kPa, similar to those obtained by conventional adsorption methods that require much larger MOF quantities (tens of milligrams). PMID- 27268427 TI - Clinical Practice Guideline for the Treatment of Pediatric Acute Gastroenteritis in the Outpatient Setting. AB - Acute gastroenteritis (AGE) is a common illness in childhood that usually can be treated in the outpatient setting. Inaccurate assessment or delayed treatment of AGE can lead to an increased risk for invasive interventions. A literature search was conducted using PubMed, CINAHL Plus, the Cochrane Library, and Embase. Results of the query were refined to narrow the focus of relevant studies for the provider caring for dehydrated children in the outpatient setting. Use of clinical dehydration scales to assess the level of dehydration and early initiation of oral rehydration therapy promote optimal patient outcomes. Oral rehydration therapy remains the best means of rehydrating, and ondansetron is a safe and effective adjunct to help children with persistent vomiting. The purpose of this practice guideline is to identify best practices for AGE in children older than 6 months with symptoms for less than 7 days who are being cared for in the outpatient setting. PMID- 27268428 TI - An Innate Immunity Pathway in the Moss Physcomitrella patens. AB - MAP kinase (MPK) cascades in Arabidopsis thaliana and other vascular plants are activated by developmental cues, abiotic stress, and pathogen infection. Much less is known of MPK functions in nonvascular land plants such as the moss Physcomitrella patens Here, we provide evidence for a signaling pathway in P. patens required for immunity triggered by pathogen associated molecular patterns (PAMPs). This pathway induces rapid growth inhibition, a novel fluorescence burst, cell wall depositions, and accumulation of defense-related transcripts. Two P. patens MPKs (MPK4a and MPK4b) are phosphorylated and activated in response to PAMPs. This activation in response to the fungal PAMP chitin requires a chitin receptor and one or more MAP kinase kinase kinases and MAP kinase kinases. Knockout lines of MPK4a appear wild type but have increased susceptibility to the pathogenic fungi Botrytis cinerea and Alternaria brassisicola Both PAMPs and osmotic stress activate some of the same MPKs in Arabidopsis. In contrast, abscisic acid treatment or osmotic stress of P. patens does not activate MPK4a or any other MPK, but activates at least one SnRK2 kinase. Signaling via MPK4a may therefore be specific to immunity, and the moss relies on other pathways to respond to osmotic stress. PMID- 27268431 TI - Quantum Chemical Insight into the Interactions and Thermodynamics Present in Choline Chloride Based Deep Eutectic Solvents. AB - We report quantum chemical calculations performed on three popular deep eutectic solvents (DESs) in order to elucidate the molecular interactions, charge transfer interactions, and thermodynamics associated with these systems. The DESs studied comprise 1:2 choline chloride/urea (reline), 1:2 choline chloride/ethylene glycol (ethaline), and 1:1 choline chloride/malonic acid (maloline). The excellent correlation between calculated and experimental vibrational spectra allowed for identification of dominant interactions in the DES systems. The DESs were found to be stabilized by both conventional hydrogen bonds and C-H...O/C-H...pi interactions between the components. The hydrogen-bonding network established in the DES is clearly distinct from that which exists within the neat hydrogen-bond donor dimer. Charge decomposition analysis indicates significant charge transfer from choline and chloride to the hydrogen-bond donor with a higher contribution from the cation, and a density of states analysis confirms the direction of the charge transfer. Consequently, the sum of the bond orders of the choline-Cl(-) interactions in the DESs correlates directly with the melting temperatures of the DESs, a correlation that offers insight into the effect of the tuning of the choline-Cl(-) interactions by the hydrogen-bond donors on the physical properties of the DESs. Finally, the differences in the vibrational entropy changes upon DES formation are consistent with the trend in the overall entropy changes upon DES formation. PMID- 27268430 TI - tRNA-Related Sequences Trigger Systemic mRNA Transport in Plants. AB - In plants, protein-coding mRNAs can move via the phloem vasculature to distant tissues, where they may act as non-cell-autonomous signals. Emerging work has identified many phloem-mobile mRNAs, but little is known regarding RNA motifs triggering mobility, the extent of mRNA transport, and the potential of transported mRNAs to be translated into functional proteins after transport. To address these aspects, we produced reporter transcripts harboring tRNA-like structures (TLSs) that were found to be enriched in the phloem stream and in mRNAs moving over chimeric graft junctions. Phenotypic and enzymatic assays on grafted plants indicated that mRNAs harboring a distinctive TLS can move from transgenic roots into wild-type leaves and from transgenic leaves into wild-type flowers or roots; these mRNAs can also be translated into proteins after transport. In addition, we provide evidence that dicistronic mRNA:tRNA transcripts are frequently produced in Arabidopsis thaliana and are enriched in the population of graft-mobile mRNAs. Our results suggest that tRNA-derived sequences with predicted stem-bulge-stem-loop structures are sufficient to mediate mRNA transport and seem to be necessary for the mobility of a large number of endogenous transcripts that can move through graft junctions. PMID- 27268432 TI - Performance evaluation of a hybrid system for efficient palm oil mill effluent treatment via an air-cathode, tubular upflow microbial fuel cell coupled with a granular activated carbon adsorption. AB - An air-cathode MFC-adsorption hybrid system, made from earthen pot was designed and tested for simultaneous wastewater treatment and energy recovery. Such design had demonstrated superior characteristics of low internal resistance (29.3Omega) and favor to low-cost, efficient wastewater treatment and power generation (55mW/m(3)) with average current of 2.13+/-0.4mA. The performance between MFC adsorption hybrid system was compared to the standalone adsorption system and results had demonstrated great pollutants removals of the integrated system especially for chemical oxygen demand (COD), biochemical oxygen demand (BOD3), total organic carbon (TOC), total volatile solids (TVS), ammoniacal nitrogen (NH3 N) and total nitrogen (TN) because such system combines the advantages of each individual unit. Besides the typical biological and electrochemical processes that happened in an MFC system, an additional physicochemical process from the activated carbon took place simultaneously in the MFC-adsorption hybrid system which would further improved on the wastewater quality. PMID- 27268429 TI - CASEIN KINASE1-LIKE PROTEIN2 Regulates Actin Filament Stability and Stomatal Closure via Phosphorylation of Actin Depolymerizing Factor. AB - The opening and closing of stomata are crucial for plant photosynthesis and transpiration. Actin filaments undergo dynamic reorganization during stomatal closure, but the underlying mechanism for this cytoskeletal reorganization remains largely unclear. In this study, we identified and characterized Arabidopsis thaliana casein kinase 1-like protein 2 (CKL2), which responds to abscisic acid (ABA) treatment and participates in ABA- and drought-induced stomatal closure. Although CKL2 does not bind to actin filaments directly and has no effect on actin assembly in vitro, it colocalizes with and stabilizes actin filaments in guard cells. Further investigation revealed that CKL2 physically interacts with and phosphorylates actin depolymerizing factor 4 (ADF4) and inhibits its activity in actin filament disassembly. During ABA-induced stomatal closure, deletion of CKL2 in Arabidopsis alters actin reorganization in stomata and renders stomatal closure less sensitive to ABA, whereas deletion of ADF4 impairs the disassembly of actin filaments and causes stomatal closure to be more sensitive to ABA Deletion of ADF4 in the ckl2 mutant partially recues its ABA insensitive stomatal closure phenotype. Moreover, Arabidopsis ADFs from subclass I are targets of CKL2 in vitro. Thus, our results suggest that CKL2 regulates actin filament reorganization and stomatal closure mainly through phosphorylation of ADF. PMID- 27268433 TI - Increased loading rates and specific methane yields facilitated by digesting grass silage at thermophilic rather than mesophilic temperatures. AB - This study was conducted to advance the understanding of thermophilic grass digestion. Late harvested grass silage was fermented at thermophilic conditions at increasing organic loading rates (OLR). Stable digestion took place at an OLR between 3 and 4gVSL(-1)d(-1). This enabled specific methane yields (SMY) as high as 405LCH4kgVS(-1). An accumulation of volatile fatty acids (VFA), accompanied by a gradual deterioration of pH, FOS/TAC (ratio of VFA to alkalinity) arose at an OLR between 5 and 7gVSL(-1)d(-1), yet inhibition did not occur. SMY decreased with reduced retention time ranging between 336 and 358LCH4kgVS(-1) at OLR 7 and 5gVSL(-1)d(-1) respectively. The biomethane efficiencies remained high (92-103%) at corresponding retention times. Comparative results indicated a superior performance with respect to higher loading and SMY as compared with mesophilic conditions. PMID- 27268434 TI - Performance evaluation of a full-scale innovative swine waste-to-energy system. AB - Intensive monitoring was carried out to evaluate the performance of a full-scale innovative swine waste-to-energy system at a commercial swine farm with 8640 heads of swine. Detailed mass balances over each unit of the system showed that the system, which includes a 7600m(3) anaerobic digester, a 65-kW microturbine, and a 4200m(3) aeration basin, was able to remove up to 92% of the chemical oxygen demand (COD), 99% of the biological oxygen demand (BOD), 77% of the total nitrogen (TN), and 82% of the total phosphorous (TP) discharged into the system as fresh pig waste. The overall biogas yield based on the COD input was 64% of the maximum theoretical, a value that indicates that even greater environmental benefits could be obtained with process optimization. Overall, the characterization of the materials fluxes in the system provides a greater understanding of the fate of organics and nutrients in large scale animal waste management systems. PMID- 27268435 TI - Overproduction of cellulase by Trichoderma reesei RUT C30 through batch-feeding of synthesized low-cost sugar mixture. AB - Cellulase is a prerequisite for the bioconversion of lignocellulosic biomass, but its high cost presents the biggest challenge. In this article, low-cost mixture was produced from glucose through the transglycosylation reaction catalyzed by beta-glucosidase for cellulase overproduction by Trichodema reesei RUT C30. As a result, cellulase titer of 90.3FPU/mL, which was more than 10 folds of that achieved with lactose as inducer, was achieved at 144h. Meanwhile, cellulase productivity was drastically increased to 627.1FPU/L/h, at least 3-5 folds higher than previously reported by the fungal species. The crude enzyme was further tested by hydrolyzing NaOH-pretreated corn stover with 15% solid loading, and 96.6g/L glucose was released with 92.6% sugar yield at 96h and 44.8g/L ethanol was obtained. PMID- 27268436 TI - Peroxide-assisted microwave activation of pyrolysis char for adsorption of dyes from wastewater. AB - In this study, mesoporous activated biochar with high surface area and controlled pore size was prepared from char obtained as a by-product of pyrolysis of Prosopis juliflora biomass. The activation was carried out by a simple process that involved H2O2 treatment followed by microwave pyrolysis. H2O2 impregnation time and microwave power were optimized to obtain biochar with high specific surface area and high adsorption capacity for commercial dyes such as Remazol Brilliant Blue and Methylene Blue. Adsorption parameters such as initial pH of the dye solution and adsorbent dosage were also optimized. Pore size distribution, surface morphology and elemental composition of activated biochar were thoroughly characterized. H2O2 impregnation time of 24h and microwave power of 600W produced nanostructured biochar with narrow and deep pores of 357m(2)g( 1) specific surface area. Langmuir and Langmuir-Freundlich isotherms described the adsorption equilibrium, while pseudo second order model described the kinetics of adsorption. PMID- 27268437 TI - Magnetite/graphene oxide nano-composite for enhancement of hydrogen production from gelatinaceous wastewater. AB - The effect of substrate to inoculum (So/Xo) ratio and supplementation of magnetite/graphene oxide (MGO) nano-composite material on hydrogen production from gelatinaceous wastewater via dark fermentation process was investigated. Results demonstrated that optimum So/Xo ratio of 1.0gCOD/gVSS achieved maximal hydrogen yield (HY) of 79.2+/-11.9mL H2/gCOD removed. Supplementation of anaerobes with 100mg/L MGO promoted HY up to 112.4+/-10.5mL H2/gCOD removed. Moreover, the degradation efficiency of carbohydrates, proteins and lipids was improved to 80.8+/-7.6, 34.4+/-2.3 and 31.4+/-2.2%, respectively. Acetate (HAc) and butyrate (HBu) concentrations increased from 102+/-6.8 to 125.3+/-6.3 and from 31.1+/-1.5 to 48.8+/-3.5mg/gVSS, respectively. However, propionate (HPr) concentration dropped from 35.9+/-2.7 to 15+/-1.3mg/gVSS. Hydrogenase enzyme activity increased 9-folds and the anaerobes elongated from ca. 1.8-2.9 to ca. 2.5-5.1MUm with MGO addition. Moreover, Proteobacteria, Firmicutes, Clostridia and Bacilli were detected with the batches supplemented with MGO. PMID- 27268438 TI - A bio-anodic filter facilitated entrapment, decomposition and in situ oxidation of algal biomass in wastewater effluent. AB - This study examined for the first time the use of bioelectrochemical systems (BES) to entrap, decompose and oxidise fresh algal biomass from an algae-laden effluent. The experimental process consisted of a photobioreactor for a continuous production of the algal-laden effluent, and a two-chamber BES equipped with anodic graphite granules and carbon-felt to physically remove and oxidise algal biomass from the influent. Results showed that the BES filter could retain ca. 90% of the suspended solids (SS) loaded. A coulombic efficiency (CE) of 36.6% (based on particulate chemical oxygen demand (PCOD) removed) was achieved, which was consistent with the highest CEs of BES studies (operated in microbial fuel cell mode (MFC)) that included additional pre-treatment steps for algae hydrolysis. Overall, this study suggests that a filter type BES anode can effectively entrap, decompose and in situ oxidise algae without the need for a separate pre-treatment step. PMID- 27268439 TI - Improving methane production from digested manure biofibers by mechanical and thermal alkaline pretreatment. AB - Animal manure digestion is associated with limited methane production, due to the high content in fibers, which are hardly degradable lignocellulosic compounds. In this study, different mechanical and thermal alkaline pretreatment methods were applied to partially degradable fibers, separated from the effluent stream of biogas reactors. Batch and continuous experiments were conducted to evaluate the efficiency of these pretreatments. In batch experiments, the mechanical pretreatment improved the degradability up to 45%. Even higher efficiency was shown by applying thermal alkaline pretreatments, enhancing fibers degradability by more than 4-fold. In continuous experiments, the thermal alkaline pretreatment, using 6% NaOH at 55 degrees C was proven to be the most efficient pretreatment method as the methane production was increased by 26%. The findings demonstrated that the methane production of the biogas plants can be increased by further exploiting the fraction of the digested manure fibers which are discarded in the post-storage tank. PMID- 27268440 TI - Oxidation of Tyrosine-Phosphopeptides by Titanium Dioxide Photocatalysis. AB - Protein phosphorylation has a key role in cell regulation. Oxidation of proteins, in turn, is related to many diseases and to aging, but the effects of phosphorylation on the oxidation of proteins and peptides have been rarely studied. The aim of this study was to examine the mechanistic effect of phosphorylation on peptide oxidation induced by titanium dioxide photocatalysis. The effect of phosphorylation was compared between nonphosphorylated and tyrosine phosphorylated peptides using electrospray tandem mass spectrometry. We observed that tyrosine was the most preferentially oxidized amino acid, but the oxidation reaction was significantly inhibited by its phosphorylation. The study also shows that titanium dioxide photocatalysis provides a fast and easy method to study oxidation reactions of biomolecules, such as peptides. PMID- 27268441 TI - Involvement of MAK-1 and MAK-2 MAP kinases in cell wall integrity in Neurospora crassa. AB - Among three MAPK disruptants of Neurospora crassa, Deltamak-1 was sensitive and Deltamak-2 was hypersensitive to micafungin, a beta-1,3-glucan synthase inhibitor, than the wild-type or Deltaos-2 strains. We identified six micafungin inducible genes that are involved in cell wall integrity (CWI) and found that MAK 1 regulated the transcription of non-anchored cell wall protein gene, ncw-1, and the beta-1,3-endoglucanase gene, bgt-2, whereas MAK-2 controlled the expression of the glycosylhydrolase-like protein gene, gh76-5, and the C4-dicarboxylate transporter gene, tdt-1. Western blotting analysis revealed that, in the wild type strain, MAK-1 was constitutively phosphorylated from conidial germination to hyphal development. In contrast, the phosphorylation of MAK-2 was growth phase dependent, and micafungin induced the phosphorylation of unphosphorylated MAK-2. It should be noted that the phosphorylation of MAK-1 was virtually abolished in the Deltamak-2 strain, but was significantly induced by micafungin, suggesting functional cross talk between MAK-1 and MAK-2 signalling pathway in CWI. PMID- 27268442 TI - Limonoids with neuroprotective activity from the stems of Clausena emarginata. AB - Two new limonoids, clauemargines M-N (1-2), together with five known compounds (3 7), were isolated from the stems of Clausena emarginata, and compounds 6 and 7 were gained from this plant for the first time. Their structures were established and elucidated on the basis of comprehensive spectroscopic analysis. The absolute configurations of 1-2 were further determined by the octant rule of saturated cyclic ketone. Compounds 1, 2, 4, and 5 showed moderate neuroprotective effects against L-glutamic acid-induced cellular damage in human neuroblastoma SK-N-SH cells at 10 MUM. PMID- 27268443 TI - [Vaccinations]. PMID- 27268445 TI - [Pneumococcal vaccination for children and adults]. AB - Pneumococci are the leading bacterial causes of respiratory tract infections, bacteremia and meningitis. Pneumococcal conjugate vaccines (PCV) are effective and safe in young children. Their introduction led to significant reductions of invasive pneumococcal disease (IPD), pneumonia, otitis media and antibiotic resistant pneumococcal infections. Beyond these effects in the vaccinated age groups, there is a reduction in nasopharyngeal pneumococcal carriage and therefore in transmission. This in turn led to marked reductions in IPD and pneumonia in non-vaccinated age groups, particularly elderly adults as evidence of herd protection. Recently it was shown that the 13-valent PCV13 is effective and safe in adults leading to the age-independent recommendation of PCV13 in all persons with risk factors. PMID- 27268444 TI - [Influenza - Not innocuous, but preventable]. AB - Influenza is an infectious disease that can be prevented by a vaccine but the readiness to vaccinate against this recurrent infection is weak in the general population. However, influenza is not always a harmless illness as illustrated in our authentic case report. Individuals with an impaired immune response, particularly pregnant women and the elderly are particularly at risk for a complicated course of influenza. But it is precisely this population, which also has an attenuated immune response to the vaccine. The limited efficacy in this target group is a potential "loss of image" for any flu vaccination campaign. This raises the question whether we should not try to motivate healthy individuals to get vaccinated, particularly if they are living or working next to vulnerable individuals. Epidemiologic data but also recent mathematical models indicate that consistent vaccination of (school-)children results in reduced mortality in elderly people. PMID- 27268446 TI - [HPV vaccination]. AB - Human Papilloma Viruses are associated with genital carcinoma (of the cervix, anus, vulva, vagina and the penis) as well as with non-genital carcinoma (oropharyngeal carcinoma) and genital warts. In Switzerland two highly efficient and safe vaccines are available. The safety of these vaccines has been repeatedly subject of controversial discussions, however so far post marketing surveillance has always been able to confirm the safety. In Switzerland girls and young women have been offered the HPV vaccination within cantonal programmes since 2008. 2015 the recommendation for the HPV-vaccination for boys and young men was issued, and starting July 1, 2016 they as well will be offered vaccination free of charge within the cantonal programmes. This article discusses the burden of disease, efficacy and safety of the vaccines and presents facts which are important for vaccinating these young people. Specifically, aspects of the decisional capacity of adolescents to consent to the vaccination are presented. Finally, the future perspective with a focus on a new vaccine with an enlarged spectrum of HPV-types is discussed. PMID- 27268447 TI - [Chickenpox and shingles: one virus, two diseases and current vaccination recommendations in Switzerland]. AB - Adults, pregnant women, premature babies and immunocompromised persons are at increased risk for varicella complications. Therefore the current Swiss vaccination recommendations against varicella include a general recommendation for 11 to 15 year old adolescents with a negative varicella history, as well as a specific recommendation for risk groups. The goal of both recommendations is to reduce varicella complications in persons most at risk. The vaccine is not universally recommended for all toddlers in Switzerland, while this is the case in some countries such as the United States. Pros and cons of different vaccination strategies, as well as possible short- and long-term effects on herpes zoster incidence are taken into account. In the United States, there was a marked decline in incidence and hospitalisations, but an increased herpes zoster incidence in the short term. Finally, public health aspects of herpes zoster, post-herpetic neuralgia and possible vaccination strategies are outlined. PMID- 27268448 TI - [Immunization against tick-borne encephalitis]. AB - Tick-borne encephalitis (TBE) is a viral infection that may cause irreversible damage to the brain and even result in death. No specific therapy exists. Active immunization is of major importance in controlling the infection. Vaccination is recommended to all adults and children > 6 years who live in endemic areas. Two inactivated vaccines are available in Switzerland. The vaccination schedule includes a basic immunization composed of 3 injections followed by boosting every 10 years. The efficacy of the vaccines has never been investigated in controlled studies, however, from indirect evidence, the vaccines are thought to cause good protection and to be safe. Local reactions at the injections site may occur in one third and mild systemic side effects in one fifth of vaccinees. Anaphylactic reactions and severe central nervous side effects are very rare. PMID- 27268449 TI - [Rabbies vaccination]. AB - With very few exceptions, rabies is occurring around the globe. The clinical course of this mammal-transmitted infection is almost universally fatal. Thus, the disease is causing more human deaths than any other zoonosis. Due to the lack of effective therapeutic options, pre- or post-exposure vaccination remains the only effective means to avoid development of fatal disease. Save and highly effective cell culture vaccines which have been available for decades provide long-lasting protection. Various vaccination schedules have been tested and are being recommended. PMID- 27268450 TI - [Which vaccinations for which travel-destination?]. AB - Several vaccinations are recommended to protect international travellers, especially to tropical countries, from diseases in other parts of the world. Firstly, the routine schedule of childhood vaccinations and booster shots according to the Swiss immunisation programme should be checked, updated or even completed. Additional vaccinations against hepatitis A and B, typhoid fever, poliomyelitis, rabies or Japanese encephalitis may be recommended. This will depend on a number of factors including the exact destination and route (developing countries, rural areas), planned activities (backpacker, family visit, business trip), duration of travel, season, age of the traveller and current health status including the current medication and previous vaccinations. Some vaccinations, such as yellow fever, may be required for travellers to certain countries and the international certificate of vaccination may even be required when entering a country from another country where yellow fever is endemic. The international certificate of vaccination (or a letter of exemption when appropriate) is considered valid only if it is administered by an approved vaccination centre. Furthermore, the meningococcal vaccination (A, C, W, Y) is required for pilgrims to Saudi Arabia. It is recommended to start the vaccinations four to six weeks before departure to ensure enough time to administer all the necessary doses for an adequate immune response. All commonly used vaccines can be administered on the same day. The basic health insurance does not usually cover travel vaccines. PMID- 27268451 TI - [Vaccinations in pregnancy - Don't miss the opportunity!]. AB - Pregnant women and neonates are prone to a variety of infections and often suffer from complicated courses of the disease. The growing knowledge on immunology and vaccinations during pregnancy has led to further development of already known strategies in protecting pregnant women and neonates in the most vulnerable moments of their lives. Vaccination during pregnancy against pertussis and influenza is safe and induces high levels of protecting antibodies in the mother. In addition, these specific antibodies are actively transferred to the fetus, protecting the newborn during the first weeks of life, when infections are often severe and associated with high morbidity and mortality. Viral infections like measles, rubella and varicella also may have devastating effects on mother and child when occurring during pregnancy. Available vaccinations (MMR, VZV) are inducing a stable and durable immunity, but are contraindicated during pregnancy, because of being live-vaccines. Therefore, every woman should be immune either by past infection or by vaccination before becoming pregnant. If susceptibility is only detected during pregnancy, vaccination should be started as soon as possible after birth. In conclusion, vaccinations during pregnancy offer a safe and efficient protection against dangerous infections for mother, fetus and newborn. PMID- 27268452 TI - [Vaccinations in patients with autoimmune diseases]. AB - The number of individuals with autoimmune diseases treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and in particular biological therapies is also rising. The autoimmune disease itself as well as the immunosuppressive therapy increases the risk of infection in this population. Particularly the risk of vaccine-preventable infections is elevated. Thus, preventing infections by the means of vaccination is of utmost importance. The Division of Infectious Diseases of the Epidemiology, Biostatistics and Prevention Institute, University of Zurich, performed a literature search on the topic of vaccinations in patients with autoimmune diseases upon request by the Swiss Federal Commission for Vaccination Issues. Overall, data are scarce. The following main points were retrieved from the literature: Inactivated vaccines are safe, but their immunogenicity may be reduced under immunosuppressive therapy. In addition to the generally recommended basic vaccinations, specific vaccinations, such as influenza and pneumococcal vaccination are indicated in these patient groups. Live vaccines are generally contraindicated under immunosuppressive therapy due to safety concerns. However, specific exceptions apply. Furthermore, certain time intervals for the administration of live vaccines after pausing or ceasing an immunosuppressive therapy should be respected. PMID- 27268453 TI - [Vaccinations for immunocompromised hosts - focussing on patients after a hematological stem cell or organ transplantation, with HIV or with functional or anatomical asplenia]. AB - Patients with an acquired immune deficiency, for example due to HIV-infection, after a solid organ or haematological stem cell transplantation or due to functional or anatomical asplenia, have a greater risk to experience severe complications or a chronic course of infection compared to healthy individuals. Vaccinations would pose an ideal primary preventive method. However, their efficacy is reduced if applied during the immunosuppressed period. Therefore, whenever possible, vaccinations should be administered before the period of immunosuppression starts - or caught up later during the period of minimal possible immunosuppression. Nevertheless, the benefit conveyed through vaccines is undisputed, particularly if indications regarding dosing of vaccines (amount and frequency of doses) are optimized according to the given state of immunosuppression. Live attenuated vaccines are contraindicated during severe immunosuppression. Serologies should still be analysed and documented however, since these vulnerable patients require passive immunization through specific or standard intravenous immunoglobulins in case of relevant exposure to the respective antigens. For all patients therefore, careful documentation and communication of previous vaccinations and serologies (protective or not) among the various medical specialties is required to optimize patient management. For all immunosuppressed patients the efficacy of polysaccharide vaccines (such as the pneumococcal and meningococcal vaccines PSV-23 and MPV-ACWY) is strongly reduced compared to the conjugated ones (PCV13 and MCV-ACWY). Therefore, contrary to most other national guidelines, the Swiss guidelines recommend to use only the conjugated versions in primary vaccination series as well as in boosters - this applies strongly for immunosuppressed patients, but is recommended also for the general population in Switzerland. Another common management recommendation specific for transplant patients is the indication to control vaccine efficacy by measuring titers. This is also indicated for hepatitis B in HIV-positive patients, but not required for any vaccine in asplenic patients. In summary, vaccines pose an important opportunity for primary and secondary prevention for vulnerable patients at highest risk of experiencing the worst forms of the diseases to be prevented. PMID- 27268454 TI - [Understanding and Handling Vaccine Hesitancy]. AB - Vaccine hesitancy is a growing concern to experts around the world and could increasingly jeopardize the success of vaccination campaigns. Ambivalence in questions of vaccination is promoted through mistrust of vaccines and providers, furthermore through the plethora of unfiltered and often contradictory information leading to uncertainty as to whom one shall believe. Individuals are also in a dilemma in issues of vaccination, having to decide if they will accept vaccines regarding only their own wellbeing or also as an act of solidarity to maintain a high level of vaccination rates in order to eradicate diseases. Finally vaccine hesitancy is also maintained by the success of vaccination. Vaccine preventable diseases have become so seldom that many individuals perceive them as negligible. The risk of vaccination then surpasses the risk of disease thus leading to the rejection of vaccination. Although those opposing vaccination comprise only a small minority of the population, their arguments seem to be heard disproportionately, influencing vaccine hesitants very strongly. On the other hand family doctors are still highly appreciated as advisors in health related issues. These health providers can play an important role in stimulating vaccine acceptance. Delivering transparent and evidence-based information on vaccination through competent communication skills helps to rebuild the dwindling trust in vaccines. Sufficient time is required for an enriching dialogue. PMID- 27268455 TI - [The benefits prevail - why electronic immunization records are advantageous to the general practitioner and his patients]. AB - Immunization coverage throughout the Swiss population is still not optimal and therefore preventable diseases such as measles have not been eliminated in Switzerland yet. In addition, new vaccination protocols are available and official recommendations are becoming increasingly complex. The website www.myvaccines.ch has been in use since 2011 with the primary goal to increase immunization coverage. This service was established by Vaccinologist Professor Claire-Anne Siegrist from the University of Geneva and is free of charge for all Swiss doctors and pharmacists. It enables general practitioners and pediatricians to document the vaccination history of their patients in a new electronic immunization record. After a simple and quick process, the web-based software proposes up-to-date recommendations of new or follow-up vaccinations following the current Swiss Immunization Plan by the Federal Department of Health. Within this single practice, 1446 files have been recorded within the past three years. As a consequence, a total of 4378 immunizations have been administered, leading to a mean of 3.03 immunizations per patient. After introducing the electronic immunization record, the rates of immunizations have increased dramatically for all antigens (factor 2.1 to 41.5). Overall, patient acceptance was high - the doctor's investment was positively recognized and his approach to patient care was perceived as modern. As a result, the practice has become competent in immunization. In summary, the positive outcome of using the electronic record highly supports the free program www.myvaccines.ch to all general practitioners and pediatricians in Switzerland. PMID- 27268456 TI - Repeated application of Modafinil and Levodopa reveals a drug-independent precise timing of spatial working memory modulation. AB - Cognition enhancing drugs often target the dopaminergic system, which is involved in learning and memory, including working memory that in turn involves mainly the prefrontal cortex and the hippocampus. In most animal models for modulations of working memory animals are pre-trained to a certain criterion and treated then acutely to test drugs effects on working memory. Thus, little is known regarding subchronic or chronic application of cognition enhancing drugs and working memory performance. Therefore we trained male rats over six days in a rewarded alternation test in a T-maze. Rats received daily injections of either modafinil or Levodopa (L-Dopa) at a lower and a higher dose 30min before training. Levodopa but not modafinil increased working memory performance during early training significantly at day 3 when compared to vehicle controls. Both drugs induced dose dependent differences in working memory with significantly better performance at low doses compared to high doses for modafinil, in contrast to L-Dopa where high dose treated rats performed better than low dose rats. Strikingly, these effects appeared only at day 3 for both drugs, followed by a decline in behavioral performance. Thus, a critical drug independent time window for dopaminergic effects upon working memory could be revealed. Evaluating the underlying mechanisms contributes to the understanding of temporal effects of dopamine on working memory performance. PMID- 27268457 TI - Decreasing Stereotypy Using NCR and DRO With Functionally Matched Stimulation: Effects on Targeted and Non-Targeted Stereotypy. AB - We conducted a series of studies on multiple forms of repetitive behavior displayed by four children with autism spectrum disorder. Study 1 showed that each participant's highest probability repetitive behavior persisted in the absence of social consequences, thereby meeting the functional definition of stereotypy. Study 2 showed that preferred, structurally matched stimulation decreased each participant's targeted (highest probability) stereotypy, as well as their non-targeted (lower probability) stereotypy. Study 3 showed that for three participants, non-contingent access to preferred stimulation decreased immediate and, to some extent, subsequent engagement in targeted and non-targeted stereotypy. For the fourth participant, non-contingent access to preferred stimulation decreased immediate engagement in the targeted stereotypy, but increased subsequent engagement in non-targeted stereotypy; this subsequent increase was attenuated by reducing the duration of access to the preferred stimulus. Study 4 showed that a trial-based differential reinforcement of other behavior (DRO) procedure systematically increased the period of time for which the targeted stereotypy was not displayed for three of three participants. In addition, results showed that the participants' non-targeted stereotypy either decreased or was unchanged when DRO was provided for the targeted stereotypy. PMID- 27268458 TI - Sex-Specific Effects of Arsenic Exposure on the Trajectory and Function of the Gut Microbiome. AB - The gut microbiome is deeply involved in numerous aspects of human health; however, it can be readily perturbed by environmental toxicants, such as arsenic. Meanwhile, the interaction among host, gut microbiome, and xenobiotics is a very complex dynamic process. Previously, we have demonstrated that gut microbiome phenotypes driven by host genetics and bacterial infection affect the responses to arsenic exposure. The role of host sex in shaping the gut microbiome raises the question whether sex plays a role in exposure-induced microbiome responses. To examine this, we used 16S rRNA sequencing and metagenomics sequencing to analyze the changes of the gut microbiome and its associated functional metagenome in both female and male C57/BL6 mice. Our results clearly demonstrated that arsenic exposure perturbed the trajectory and function of the gut microbiome in a sex-specific manner. PMID- 27268459 TI - Genetic determinants and stroke in children with sickle cell disease. AB - OBJECTIVE: To verify genetic determinants associated with stroke in children with sickle cell disease (SCD). METHODS: Prospective cohort with 110 children submitted to neonatal screening by the Neonatal Screening Program, between 1998 and 2007, with SCD diagnosis, followed at a regional reference public service for hemoglobinopathies. The analyzed variables were type of hemoglobinopathy, gender, coexistence with alpha thalassemia (alpha-thal), haplotypes of the beta globin chain cluster, and stroke. The final analysis was conducted with 66 children with sickle cell anemia (SCA), using the chi-squared test in the program SPSS(r) version 14.0. RESULTS: Among children with SCD, 60% had SCA. The prevalence of coexistence with alpha-thal was 30.3% and the Bantu haplotype (CAR) was identified in 89.2%. The incidence of stroke was significantly higher in those with SCA (27.3% vs. 2.3%; p=0.001) and males (24.1% vs. 9.6%; p=0.044). The presence of alpha-thal (p=0.196), the CAR haplotype (p=0.543), and socioeconomic factors were not statistically significant in association with the occurrence of stroke. CONCLUSION: There is a high incidence of stroke in male children and in children with SCA. Coexistence with alpha-thal and haplotypes of the beta globin chain cluster did not show any significant association with stroke. The heterogeneity between previously evaluated populations, the non-reproducibility between studies, and the need to identify factors associated with stroke in patients with SCA indicate the necessity of conducting further research to demonstrate the relevance of genetic factors in stroke related to SCD. PMID- 27268460 TI - Intrafamilial heterogeneity of congenital optic disc pit maculopathy. AB - BACKGROUND: Optic disc pit is a very rare clinical entity. The main complication of this condition is the maculopathy. Report of cases: A 40-year-old Caucasian man and his 6-year-old daughter underwent a complete ophthalmological examination. In both cases ophthalmoscopy examination showed a bilateral white yellow oval depression in the optic disc. Optical coherence tomography showed maculopathy with different degrees of severity in the two cases. Microperimetry and multifocal-electroretinography showed different degrees of retinal dysfunction in both cases. Molecular genetic analysis was performed and the possible pathogenic role of the MIR204 gene was excluded. DISCUSSION: The findings of our familial cases support the hypothesis that optic disc pit associated with maculopathy could be a genetic disease with an autosomal dominant inheritance pattern. Optical coherence tomography is the most helpful diagnostic tool to assess maculopathy associated with optic disc pit. Microperimetry and multifocal-electroretinography are useful for the diagnosis of macular dysfunction in the early stages, and for the prognosis and follow-up of optic disc pit-maculopathy which is the main cause of visual impairment in these patients. Furthermore, in consideration of the variable expressivity and disease severity reported in our cases, genetic anticipation may be hypothesized. PMID- 27268461 TI - Dissolution enhancement of tadalafil by liquisolid technique. AB - This study aimed to enhance the dissolution of tadalafil, a poorly water-soluble drug by applying liquisolid technique. The effects of two critical formulation variables, namely drug concentration (17.5% and 35%, w/w) and excipients ratio (10, 15 and 20) on dissolution rates were investigated. Pre-compression tests, including particle size distribution, flowability determination, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and scanning electron microscopy (SEM), were carried out to investigate the mechanism of dissolution enhancement. Tadalafil liquisolid tablets were prepared and their quality control tests, dissolution study, contact angle measurement, Raman mapping, and storage stability test were performed. The results suggested that all the liquisolid tablets exhibited significantly higher dissolution rates than the conventional tablets and pure tadalafil. FT-IR spectrum reflected no drug-excipient interactions. DSC and XRD studies indicated reduction in crystallinity of tadalafil, which was further confirmed by SEM and Raman mapping outcomes. The contact angle measurement demonstrated obvious increase in wetting property. Taken together, the reduction of particle size and crystallinity, and the improvement of wettability were the main mechanisms for the enhanced dissolution rate. No significant changes were observed in drug crystallinity and dissolution behavior after storage based on XRD, SEM and dissolution results. PMID- 27268462 TI - Disintegration of Waste Activated Sludge by Thermally-Activated Persulfates for Enhanced Dewaterability. AB - Oxidation by persulfates at elevated temperatures (thermally activated persulfates) disintegrates bacterial cells and extracellular polymeric substances (EPS) composing waste-activated sludge (WAS), facilitating the subsequent sludge dewatering. The WAS disintegration process by thermally activated persulfates exhibited different behaviors depending on the types of persulfates employed, that is, peroxymonosulfate (PMS) versus peroxydisulfate (PDS). The decomposition of PMS in WAS proceeded via a two-phase reaction, an instantaneous decomposition by the direct reaction with the WAS components followed by a gradual thermal decay. During the PMS treatment, the WAS filterability (measured by capillary suction time) increased in the initial stage but rapidly stagnated and even decreased as the reaction proceeded. In contrast, the decomposition of PDS exhibited pseudo first-order decay during the entire reaction, resulting in the greater and steadier increase in the WAS filterability compared to the case of PMS. The treatment by PMS produced a high portion of true colloidal solids (<1 MUm) and eluted soluble and bound EPS, which is detrimental to the WAS filterability. However, the observations regarding the dissolved organic carbon, ammonium ions, and volatile suspended solids collectively indicated that the treatment by PMS more effectively disintegrated WAS compared to PDS, leading to higher weight (or volume) reduction by postcentrifugation. PMID- 27268463 TI - The effect of different foot and hand set-up positions on backstroke start performance. AB - Foot and hand set-up position effects were analysed on backstroke start performance. Ten swimmers randomly completed 27 starts grouped in trials (n = 3) of each variation, changing foot (totally immersed, partially and totally emerged) and hand (lowest, highest horizontal and vertical) positioning. Fifteen cameras recorded kinematics, and four force plates collected hands and feet kinetics. Standardised mean difference and 95% confidence intervals were used. Variations with feet immersed have shown lower vertical centre of mass (CM) set up position (0.16 m), vertical impulse exerted at the hands, horizontal and vertical impulse exerted at the feet (0.28, 0.41, 0.16 N/BW.s, respectively) than feet emerged with hands horizontal and vertically positioned. Most variations with feet partially emerged exhibited higher and lesser vertical impulse exerted at hands than feet immersed and emerged (e.g. vertical handgrip, 0.13, 0.15 N/BW.s, respectively). Variation with feet emerged and hands on the lowest horizontal handgrip depicted shorter horizontal (0.23, 0.26 m) and vertical CM positioning at flight (0.16, 0.15 m) than the highest horizontal and vertical handgrip, respectively. Start variations have not affected 15-m time. Variations with feet partially or totally emerged depicted advantages, but focusing on the entry and underwater biomechanics is relevant for a shorter start time. PMID- 27268464 TI - Management of complex orbital fractures. AB - The treatment of orbital injuries has evolved considerably over the last two decades. We describe strategies involved in the emergency management of orbital injuries, the use of imaging, preformed and customised materials for reconstruction, and endoscopic techniques. PMID- 27268465 TI - Chronic Inflammation and Premenstrual Syndrome: A Missing Link Found? PMID- 27268466 TI - Conjoint influence of mind-wandering and sleepiness on task performance. AB - Recent research suggests that sleepiness and mind-wandering-the experience of thoughts that are both stimulus-independent and task-unrelated-frequently co occur and are both associated with poorer cognitive functioning. Whether these two phenomena have distinguishable effects on task performance remains unknown, however. To investigate this question, we used the online experience sampling of mind-wandering episodes and subjective sleepiness during a laboratory task (the Sustained Attention to Response Task; SART), and also assessed mind-wandering frequency and sleep-related disturbances in daily life using self-report questionnaires. The results revealed that the tendency to experience mind wandering episodes during the SART and daily life was associated with higher levels of daytime sleepiness and sleep-related disturbances. More important, however, mind-wandering and sleepiness were independent predictors of SART performance at both the within- and between-individuals levels. These findings demonstrate that, although mind-wandering and sleepiness frequently co-occur, these two phenomena have distinguishable and additive effects on task performance. (PsycINFO Database Record PMID- 27268467 TI - Free groin flap for aesthetic and functional donor-site closure of the anterolateral thigh flap. AB - BACKGROUND AND AIM: Better methods for anterolateral thigh flap donor-site reconstruction are desirable in cases when direct closure is impossible. Multiple surgical strategies have been attempted, and each has its shortcomings. The use of a contralateral free groin flap to repair the anterolateral thigh flap donor site is investigated in this report. METHODS: From October 2015 to February 2016, free groin flaps were harvested on six patients for aesthetic and functional donor-site closure of the anterolateral thigh flap, which could not be directly closed. In these cases, the reverse-flow distal portion of the descending branch of the lateral circumflex femoral artery and vein were used as recipient vessels and anastomosed to the superficial circumflex iliac artery and vein, respectively. RESULTS: One flap had presented a few blisters on the distal margin; the other five flaps fully survived without any complications. Patients were highly satisfied with the aesthetic outcomes of both the anterolateral thigh area and the groin site. CONCLUSION: Although with theoretical risks of compromised venous blood flow, free groin flaps are an effective strategy for closure of massive anterolateral donor-site defects and can be safely performed with thoughtful planning and meticulous microsurgical techniques. PMID- 27268468 TI - Low frequency dove coos vary across noise gradients in an urbanized environment. AB - Urbanization poses a challenge to bird communication due to signal masking by ambient noise and reflective surfaces that lead to signal degradation. Bird species (especially oscines) have been shown to alter their singing behaviour to increase signal efficiency in highly urbanized environments. However, few studies on the effects of noise on song structure have included birds with low frequency vocal signals which may be especially vulnerable to noise pollution due to significant frequency overlap of their signals with traffic noise. We compared the perch coos of spotted doves (Streptopelia chinensis), a species with very low frequency vocalizations, in different background noise levels across urban and peri-urban areas in Hong Kong. We documented a 10% upward shift in the minimum frequency of coos of spotted doves across the noise gradient (a relatively small but significant shift), and a reduced maximum frequency in urban habitats with a higher density of built up area. Hong Kong doves had significantly higher minimum and maximum frequencies than doves from throughout their range (from mostly rural sites). Our results indicate that urban species with extremely low sound frequencies such as doves can alter their vocalizations in response to variable urban acoustic environments. PMID- 27268469 TI - Repurposing auranofin as an antifungal: In vitro activity against a variety of medically important fungi. AB - Repositioning old drugs can significantly decrease the time and effort that it takes to develop novel antifungal therapeutics, which represents a pressing and unmet clinical need due to the devastating nature of fungal infections. We have previously described the activity of auranofin, a gold thiol compound used to treat rheumatoid arthritis, against Candida albicans biofilms. Here we evaluate its antifungal spectrum of action and describe its activity against a variety of medically important fungi. PMID- 27268471 TI - Walking as a Contributor to Physical Activity in Healthy Older Adults: 2 Week Longitudinal Study Using Accelerometry and the Doubly Labeled Water Method. AB - BACKGROUND: Physical activity is recommended to promote healthy aging. Defining the importance of activities such as walking in achieving higher levels of physical activity might provide indications for interventions. OBJECTIVE: To describe the importance of walking in achieving higher levels of physical activity in older adults. METHODS: The study included 42 healthy subjects aged between 51 and 84 years (mean body mass index 25.6 kg/m(2) [SD 2.6]). Physical activity, walking, and nonwalking activity were monitored with an accelerometer for 2 weeks. Physical activity was quantified by accelerometer-derived activity counts. An algorithm based on template matching and signal power was developed to classify activity counts into nonwalking counts, short walk counts, and long walk counts. Additionally, in a subgroup of 31 subjects energy expenditure was measured using doubly labeled water to derive physical activity level (PAL). RESULTS: Subjects had a mean PAL of 1.84 (SD 0.19, range 1.43-2.36). About 20% of the activity time (21% [SD 8]) was spent walking, which accounted for about 40% of the total counts (43% [SD 11]). Short bouts composed 83% (SD 9) of walking time, providing 81% (SD 11) of walking counts. A stepwise regression model to predict PAL included nonwalking counts and short walk counts, explaining 58% of the variance of PAL (standard error of the estimate=0.12). Walking activities produced more counts per minute than nonwalking activities (P<.001). Long walks produced more counts per minute than short walks (P=.001). Nonwalking counts were independent of walking counts (r=-.05, P=.38). CONCLUSIONS: Walking activities are a major contributor to physical activity in older adults. Walking activities occur at higher intensities than nonwalking activities, which might prevent individuals from engaging in more walking activity. Finally, subjects who engage in more walking activities do not tend to compensate by limiting nonwalking activities. TRIAL REGISTRATION: ClinicalTrials.gov NCT01609764; https://clinicaltrials.gov/ct2/show/NCT01609764 (Archived by WebCite at http://www.webcitation.org/6grls0wAp). PMID- 27268472 TI - Racial and Ethnic Health Disparities Among People With Intellectual and Developmental Disabilities. AB - Racial and ethnic health disparities are a pervasive public health problem. Emerging research finds similar health disparities among people with intellectual and developmental disabilities (IDD) compared to nondisabled adults. However, few studies have examined racial and ethnic health disparities among adults with IDD. Using national data, we examined racial and ethnic disparities in health status among adults with IDD, and investigated differences in health status between adults with IDD and nondisabled adults within each racial and ethnic group. We found that Latino and Black adults with IDD had worse health outcomes compared to White adults with IDD, and Latino and Black adults with IDD had worse health outcomes than nondisabled adults from the same racial and ethnic group. PMID- 27268470 TI - Cardiovascular effects of anti-diabetes drugs. AB - INTRODUCTION: Cardiovascular disease remains the major contributor to morbidity and mortality in diabetes. From the need to reduce cardiovascular risk in diabetes and to ensure that such risk is not exacerbated by drug treatments, governmental regulators and drug manufacturers have focused on clinical trials evaluating cardiovascular outcomes. AREAS COVERED: Findings from mechanistic and clinical trials of biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors will be reviewed. These drug classes will be compared within the context of available cardiovascular outcomes data. Clinical implications of new study regulations will be examined. EXPERT OPINION: Recent cardiovascular studies provide a more comprehensive evaluation of specific anti-diabetes therapy in individuals with high cardiovascular risk. Long-term effects of anti-hyperglycemic agents in patients with lower cardiovascular risk are still speculative. Historical data supports continued use of metformin as a first-line agent. DPP-4 inhibitors and GLP-1 receptor agonists appear to have neutral effects on cardiovascular outcomes. The significantly decreased cardiovascular risk associated with empagliflozin SGLT-2 inhibitor therapy is impressive and may change how practitioners prescribe add-on therapy to metformin. PMID- 27268474 TI - Development of a Brief Intervention to Improve Knowledge of Autism and Behavioral Strategies Among Parents in Tanzania. AB - Despite the global presence of autism spectrum disorder (ASD), a paucity of treatment services exists in Tanzania and other low- and middle-income countries. The effect of delayed or low-quality treatments is enduring and contributes to lifelong variability in ASD-related functional impairments. Service disparities in Tanzania derive in part from a widespread lack of national ASD knowledge. Historically, in Western countries, parents have played a major role in increasing ASD awareness, advancing research, and encouraging empirically supported treatments. In the absence of established treatment services, parents of children with ASD have also learned to implement behavioral interventions to reduce the widening skills gaps. This article describes the development of an intervention designed to inform parents in Tanzania about ASD and empirically supported behavioral strategies. Preliminary data, collected from a clinical implementation with 29 Tanzanian families of children diagnosed with ASD or general developmental delays, support the initial feasibility and acceptability of this intervention. This brief intervention may help to ameliorate treatment disparities due to insufficient regional knowledge, language barriers, or limited service availability and may help improve functional outcomes among Tanzanian children with ASD. PMID- 27268473 TI - Who Am I? A Life Story Intervention for Persons With Intellectual Disability and Psychiatric Problems. AB - This article describes an innovative intervention based on narrative and life review therapy that is tailored to people with intellectual disability (ID) and psychiatric problems. The current study provides a first evaluation of the intervention. A symptom checklist (SCL-90) was used in a pre- and post-follow-up design, and a qualitative evaluation of the intervention was carried out with 25 participants. Results showed large changes in psychiatric symptoms, in particular on depression, anxiety, obsessive-compulsive disorder, and interpersonal sensitivity. Participants were mainly positive in their general explicit evaluations of the therapy as well as on personal learning points, intervention specific, group-related, and therapist-related aspects. It is concluded that the intervention is promising for the treatment of people with ID and psychiatric complaints. PMID- 27268475 TI - Preparing Tomorrow's Doctors to Care for Patients With Autism Spectrum Disorder. AB - People with autism spectrum disorder (ASD) and other developmental disabilities have poorer health and face unique barriers to health care compared to people without disabilities. These health disparities can be partially attributed to physicians' limited knowledge about caring for patients with developmental disabilities. The purpose of this study was to determine the effectiveness of ASD training for medical students. Our training included a lecture and a panel presentation that featured people with ASD and family members. Students reported improved knowledge, skills, confidence, and comfort in caring for patients with ASD. PMID- 27268476 TI - Creating a SIS-A Annual Review Protocol to Determine the Need for Reassessment. AB - The Supports Intensity Scale - Adult Version (SIS-A) has been widely adopted throughout North America and the world since its publication a little over a decade ago. Many organizations and jurisdictions operate under regulations that require an annual assessment of people who receive services and supports that are financed through public funds. The time and energy devoted to an annual SIS-A reassessment has become a concern in cases where the resulting information is largely redundant with information from a prior assessment. This article presents findings from an investigation of two approaches to creating a protocol to assist SIS-A users in distinguishing situations where there is a high likelihood that support needs have not changed in meaningful ways from situations where there is a reasonable possibility that support needs have changed. The SIS-A Annual Review Protocol was created based on these analyses as well as consideration of conceptual issues associated with support needs assessment. Ways in which this protocol might be used, as well as data that need to be collected to evaluate its usefulness, are discussed. PMID- 27268479 TI - Childhood-onset ATP1A3-related conditions: Report of two new cases of phenotypic spectrum. PMID- 27268481 TI - SNF2H interacts with XRCC1 and is involved in repair of H2O2-induced DNA damage. AB - The protein XRCC1 has no inherent enzymatic activity, and is believed to function in base excision repair as a dedicated scaffold component that coordinates other DNA repair factors. Repair foci clearly represent the recruitment and accumulation of DNA repair factors at sites of damage; however, uncertainties remain regarding their organization in the context of nuclear architecture and their biological significance. Here we identified the chromatin remodeling factor SNF2H/SMARCA5 as a novel binding partner of XRCC1, with their interaction dependent on the casein kinase 2-mediated constitutive phosphorylation of XRCC1. The proficiency of repairing H2O2-induced damage was strongly impaired by SNF2H knock-down, and similar impairment was observed with knock-down of both XRCC1 and SNF2H simultaneously, suggesting their role in a common repair pathway. Most SNF2H exists in the nuclear matrix fraction, forming salt extraction-resistant foci-like structures in unchallenged nuclei. Remarkably, damage-induced formation of both PAR and XRCC1 foci depended on SNF2H, and the PAR and XRCC1 foci co localized with the SNF2H foci. We propose a model in which a base excision repair complex containing damaged chromatin is recruited to specific locations in the nuclear matrix for repair, with this recruitment mediated by XRCC1-SNF2H interaction. PMID- 27268480 TI - Physical equivalency of wild type and galactose alpha 1,3 galactose free porcine pericardium; a new source material for bioprosthetic heart valves. AB - Humans make high levels of antibody to carbohydrates with terminal galactose alpha 1,3 galactose (Gal) modifications. This Gal antigen is widely expressed in other mammals and is present on an array of current animal derived biomedical devices including bioprosthetic heart valves. There is growing interest in using Gal-free animal tissues from Gal knockout pigs (GTKO) as these tissues would not be affected by anti-Gal antibody mediated injury. In this study we compare the composition and biophysical characteristics of glutaraldehyde fixed porcine pericardium from standard and GTKO pigs. We show that with the exception of the Gal antigen which is only present in standard pig tissue both GTKO and standard pig tissue have the same general morphology and collagen content. Moreover uniaxial stress testing and suture retention testing indicate the tissues are equivalent in tensile strength. These studies indicate that genetic disruption of the alpha-galactosyltransferase (GGTA-1) which blocks synthesis of the Gal antigen has no significant impact on the structural integrity of porcine pericardium and suggest that this tissue could be directly substituted for standard pig pericardium in biomedical devices such as bioprosthetic heart valves. STATEMENT OF SIGNIFICANCE: Surgical heart valve replacement is a proven life saving therapy to treat heart valve dysfunction due to birth defects, infection and the effects of aging. Bioprosthetic heart valves (BHV) made from glutaraldehyde fixed animal tissues are an effective durable therapy in older patients (>60years) but exhibit age-dependent structural valve degeneration (SVD) in younger patients (<60years). SVD is principally caused by BHV calcification. Immune injury contributes to age-dependent SVD through the interaction of galactose alpha 1,3 galactose (Gal) a dominant xenogeneic antigen present on commercial BHVs and universally abundant human anti-Gal antibody. This study measures the tissue equivalency between standard pig pericardium and Gal-free pericardium from genetically modified pigs as a first step towards making Gal free BHVs. PMID- 27268482 TI - Biohydrogen and carboxylic acids production from wheat straw hydrolysate. AB - Hydrolyzed wheat straw was converted into carboxylic acids and biohydrogen using digesting bacteria. The fermentations were carried out using both free and membrane-encased thermophilic bacteria (55 degrees C) at various OLRs (4.42 17.95g COD/L.d), in semi-continuous conditions using one or two bioreactors in a series. The highest production of biohydrogen and acetic acid was achieved at an OLR of 4.42g COD/L.d, whilst the highest lactic acid production occurred at an OLR of 9.33g COD/L.d. Furthermore, the bioreactor with both free and membrane encased cells produced 60% more lactic acid compared to the conventional, free cell bioreactor. In addition, an increase of 121% and 100% in the production of acetic and isobutyric acid, respectively, was achieved in the 2nd-stage bioreactor compared to the 1st-stage bioreactor. PMID- 27268483 TI - An ultra-high density genetic linkage map of perennial ryegrass (Lolium perenne) using genotyping by sequencing (GBS) based on a reference shotgun genome assembly. AB - BACKGROUND AND AIMS: High density genetic linkage maps that are extensively anchored to assembled genome sequences of the organism in question are extremely useful in gene discovery. To facilitate this process in perennial ryegrass (Lolium perenne L.), a high density single nucleotide polymorphism (SNP)- and presence/absence variant (PAV)-based genetic linkage map has been developed in an F2 mapping population that has been used as a reference population in numerous studies. To provide a reference sequence to which to align genotyping by sequencing (GBS) reads, a shotgun assembly of one of the grandparents of the population, a tenth-generation inbred line, was created using Illumina-based sequencing. METHODS: The assembly was based on paired-end Illumina reads, scaffolded by mate pair and long jumping distance reads in the range of 3-40 kb, with >200-fold initial genome coverage. A total of 169 individuals from an F2 mapping population were used to construct PstI-based GBS libraries tagged with unique 4-9 nucleotide barcodes, resulting in 284 million reads, with approx. 1.6 million reads per individual. A bioinformatics pipeline was employed to identify both SNPs and PAVs. A core genetic map was generated using high confidence SNPs, to which lower confidence SNPs and PAVs were subsequently fitted in a straightforward binning approach. KEY RESULTS: The assembly comprises 424 750 scaffolds, covering 1.11 Gbp of the 2.5 Gbp perennial ryegrass genome, with a scaffold N50 of 25 212 bp and a contig N50 of 3790 bp. It is available for download, and access to a genome browser has been provided. Comparison of the assembly with available transcript and gene model data sets for perennial ryegrass indicates that approx. 570 Mbp of the gene-rich portion of the genome has been captured. An ultra-high density genetic linkage map with 3092 SNPs and 7260 PAVs was developed, anchoring just over 200 Mb of the reference assembly. CONCLUSIONS: The combined genetic map and assembly, combined with another recently released genome assembly, represent a significant resource for the perennial ryegrass genetics community. PMID- 27268484 TI - Organellar phylogenomics of an emerging model system: Sphagnum (peatmoss). AB - BACKGROUND AND AIMS: Sphagnum-dominated peatlands contain approx. 30 % of the terrestrial carbon pool in the form of partially decomposed plant material (peat), and, as a consequence, Sphagnum is currently a focus of studies on biogeochemistry and control of global climate. Sphagnum species differ in ecologically important traits that scale up to impact ecosystem function, and sequencing of the genome from selected Sphagnum species is currently underway. As an emerging model system, these resources for Sphagnum will facilitate linking nucleotide variation to plant functional traits, and through those traits to ecosystem processes. A solid phylogenetic framework for Sphagnum is crucial to comparative analyses of species-specific traits, but relationships among major clades within Sphagnum have been recalcitrant to resolution because the genus underwent a rapid radiation. Herein a well-supported hypothesis for phylogenetic relationships among major clades within Sphagnum based on organellar genome sequences (plastid, mitochondrial) is provided. METHODS: We obtained nucleotide sequences (273 753 nucleotides in total) from the two organellar genomes from 38 species (including three outgroups). Phylogenetic analyses were conducted using a variety of methods applied to nucleotide and amino acid sequences. The Sphagnum phylogeny was rooted with sequences from the related Sphagnopsida genera, Eosphagnum and Flatbergium KEY RESULTS: Phylogenetic analyses of the data converge on the following subgeneric relationships: (Rigida (((Subsecunda) (Cuspidata)) ((Sphagnum) (Acutifolia))). All relationships were strongly supported. Species in the two major clades (i.e. Subsecunda + Cuspidata and Sphagnum + Acutifolia), which include >90 % of all Sphagnum species, differ in ecological niches and these differences correlate with other functional traits that impact biogeochemical cycling. Mitochondrial intron presence/absence are variable among species and genera of the Sphagnopsida. Two new nomenclatural combinations are made, in the genera Eosphagnum and Flatbergium CONCLUSIONS: Newly resolved relationships now permit phylogenetic analyses of morphological, biochemical and ecological traits among Sphagnum species. The results clarify long-standing disagreements about subgeneric relationships and intrageneric classification. PMID- 27268485 TI - The remarkable stomata of horsetails (Equisetum): patterning, ultrastructure and development. AB - BACKGROUND AND AIMS: The stomata of Equisetum - the sole extant representative of an ancient group of land plants - are unique with respect to both structure and development, yet little is known about details of ultrastructure and patterning, and existing accounts of key developmental stages are conflicting. METHODS: We used light and electron microscopy to examine mature stomata and stomatal development in Equisetum myriochaetum, and compared them with other land plants, including another putative fern relative, Psilotum We reviewed published reports of stomatal development to provide a comprehensive discussion of stomata in more distantly related taxa. KEY RESULTS: Stomatal development in Equisetum is basipetal and sequential in strict linear cell files, in contrast with Psilotum, in which stomatal development occurs acropetally. In Equisetum, cell asymmetry occurs in the axial stomatal cell file, resulting in a meristemoidal mother cell that subsequently undergoes two successive asymmetric mitoses. Each stomatal cell complex is formed from a single precursor meristemoid, and consists of four cells: two guard cells and two mesogene subsidiary cells. Late periclinal divisions occur in the developing intervening cells. CONCLUSIONS: In addition to the unique mature structure, several highly unusual developmental features include a well-defined series of asymmetric and symmetric mitoses in Equisetum, which differs markedly from Psilotum and other land plants. The results contribute to our understanding of the diverse patterns of stomatal development in land plants, including contrasting pathways to paracytic stomata. They add to a considerable catalogue of highly unusual traits of horsetails - one of the most evolutionarily isolated land-plant taxa. PMID- 27268490 TI - Differences in incomes of physicians in the United States by race and sex: observational study. AB - OBJECTIVES: To estimate differences in annual income of physicians in the United States by race and sex adjusted for characteristics of physicians and practices. DESIGN: Cross sectional survey study. SETTING: Nationally representative samples of US physicians. PARTICIPANTS: The 2000-13 American Community Survey (ACS) included 43 213 white male, 1698 black male, 15 164 white female, and 1252 black female physicians. The 2000-08 Center for Studying Health System Change (HSC) physician surveys included 12 843 white male, 518 black male, 3880 white female, and 342 black female physicians. MAIN OUTCOME MEASURES: Annual income adjusted for age, hours worked, time period, and state of residence (from ACS data). Income was adjusted for age, specialty, hours worked, time period, years in practice, practice type, and percentage of revenue from Medicare/Medicaid (from HSC physician surveys). RESULTS: White male physicians had a higher median annual income than black male physicians, whereas race was not consistently associated with median income among female physicians. For example, in 2010-13 in the ACS, white male physicians had an adjusted median annual income of $253 042 (95% confidence interval $248 670 to $257 413) compared with $188 230 ($170 844 to $205 616) for black male physicians (difference $64 812; P<0.001). White female physicians had an adjusted median annual income of $163 234 ($159 912 to 166 557) compared with $152 784 ($137 927 to $167 641) for black female physicians (difference $10 450; P=0.17). $100 000 is currently equivalent to about L69 000 (?89 000). Patterns were unaffected by adjustment for specialty and characteristics of practice in the HSC physician surveys. CONCLUSIONS: White male physicians earn substantially more than black male physicians, after adjustment for characteristics of physicians and practices, while white and black female physicians earn similar incomes to each other, but significantly less than their male counterparts. Whether these differences reflect disparities in job opportunities is important to determine. PMID- 27268491 TI - Acute disseminated encephalomyelitis in a case of autoimmune haemolytic anaemia: a rare association. AB - Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that may occur in a postvaccination condition or as a parainfectious encephalomyelitis. It is almost always monophasic. The underlying pathogenesis of ADEM may include perivascular inflammation, oedema and demyelination in the central nervous system. We present a case of a 15-year-old girl who was diagnosed as having ADEM, as well as detected to be a follow-up case of autoimmune haemolytic anaemia on steroid treatment. She presented with progressive weakness of the right lower limb for the past 4 days. MRI showed multiple subcortical lesions of varying size showing hyperintensities in T2 fluid-attenuated inversion recovery (FLAIR). The patient responded well to steroid therapy. No residual lesion was found on follow up. Very few cases have been found with this rare association in the literature. PMID- 27268492 TI - Atypical eye complication in Takayasu's arteritis. PMID- 27268493 TI - Low back pain after a dental procedure: a case of Streptococcus viridans vertebral osteomyelitis. AB - Vertebral osteomyelitis due to Streptococcus viridans following a dental procedure is a rarely reported phenomenon. We discuss the case of a 67-year-old immunocompetent woman who presented with low back pain of 3 weeks duration associated with subjective fever and chills. On admission, the MRI of the lumbar spine showed L5-S1 vertebral osteomyelitis with associated paravertebral and epidural abscesses. Subsequently, detailed history was retaken and the patient reported having had a maxillary tooth extraction followed by a dental implant 2 months prior to the onset of her symptoms. Blood and abscess fluid cultures grew S. viridans Transthoracic echocardiogram showed no evidence of endocarditis. The patient was started on intravenous ceftriaxone but her treatment course was complicated by agranulocytosis requiring a switch to vancomycin. She required a total of 9 weeks of intravenous antibiotics for complete clinical cure. PMID- 27268494 TI - Treatment Fidelity Among Family Health Promoters Delivering a Physical Activity and Nutrition Intervention to Immigrant and Refugee Families. AB - Lack of treatment fidelity can be an important source of variation affecting the credibility and utility of outcomes from behavioral intervention research. Development and implementation of a well-designed treatment fidelity plan, especially with research involving underserved populations, requires careful conceptualization of study needs in conjunction with what is feasible in the population. The purpose of this article is to review a fidelity-monitoring plan consistent with the National Institutes of Health Behavior Change Consortium guidelines (e.g., design, training, delivery, receipt, and enactment) for an intervention trial designed to improve physical activity and nutrition among immigrant and refugee families. Description of the fidelity monitoring plan is provided and challenges related to monitoring treatment fidelity in a community based participatory intervention for immigrant and refugee families are discussed. PMID- 27268495 TI - What Does It Mean for Something to Be "Scientific"? Community Understandings of Science, Educational Attainment, and Community Representation Among a Sample of 25 CBPR Projects. AB - Community-based participatory research (CBPR) seeks to conduct relevant, sustainable research that is tailored to the needs of the communities with which it is engaged through equitable collaboration between community representatives and professional researchers. Like other participatory approaches to research and planning, CBPR has been criticized for the potential to engage a biased sample of community representatives and, thereby, undermine the fundamental purpose of the approach. Moreover, the varying educational levels and areas of expertise, especially regarding science literacy, among those participating in CBPR has raised concern about the ability for true collaboration to exist within CBPR projects. This article presents findings from a qualitative study of 25 CBPR research projects and explores matters of science literacy, community representation, and the nature of CBPR. Ultimately, it is suggested that those who engage in CBPR should carefully consider the potential for biased community representation and seek to purposely and mindfully avoid any partiality. PMID- 27268496 TI - Surgical anatomy of the spinal accessory nerve: review of the literature and case report of a rare anatomical variant. AB - OBJECTIVE: To evaluate the prevalence of variations in the anatomical route of the spinal accessory nerve from the base of the skull to the point where it enters the trapezius muscle. A case report is used to demonstrate an example of a rare but clinically important anatomical variant of this nerve. METHODS: An independent review of the literature using Medline, PubMed and Q Read databases was performed using combinations of terms including 'spinal accessory nerve', 'anatomy', 'surgical anatomy', 'anatomical variant', 'cranial nerve XI' and 'shoulder syndrome'. RESULTS: Our report demonstrates marked variation in spinal accessory nerve anatomy. At the point of crossing over the internal jugular vein, the spinal accessory nerve passes most commonly laterally (anterior) to the internal jugular vein. The reported incidence of this lateral relationship varies from 67 to 96 per cent. The nerve can also pierce the internal jugular vein, as demonstrated in our case study, with incidence ranging from 0.48 to 3.3 per cent. CONCLUSION: Anatomical variations of the spinal accessory nerve are not uncommon, and it is important for the surgeon to be aware of such variations when undertaking surgery in both the anterior and posterior triangles of the neck. PMID- 27268497 TI - The TOR signaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA. AB - Pseudouridine (Psi) has been identified in various types of RNAs, including mRNA, rRNA, tRNA, snRNA, and many other noncoding RNAs. We have previously shown that RNA pseudouridylation, like DNA and protein modifications, can be induced by stress. For instance, growing yeast cells to saturation induces the formation of Psi93 in U2 snRNA. Here, we further investigate this inducible RNA modification. We show that switching yeast cells from nutrient-rich medium to different nutrient-deprived media (including water) results in the formation of Psi93 in U2 snRNA. Using gene deletion/conditional depletion as well as rapamycin treatment, we further show that the TOR signaling pathway, which controls cell entry into stationary phase, regulates Psi93 formation. The RAS/cAMP signaling pathway, which parallels the TOR pathway, plays no role in this inducible modification. PMID- 27268498 TI - Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits. AB - Although neuronal regeneration is a highly energy-demanding process, axonal mitochondrial transport progressively declines with maturation. Mature neurons typically fail to regenerate after injury, thus raising a fundamental question as to whether mitochondrial transport is necessary to meet enhanced metabolic requirements during regeneration. Here, we reveal that reduced mitochondrial motility and energy deficits in injured axons are intrinsic mechanisms controlling regrowth in mature neurons. Axotomy induces acute mitochondrial depolarization and ATP depletion in injured axons. Thus, mature neuron-associated increases in mitochondria-anchoring protein syntaphilin (SNPH) and decreases in mitochondrial transport cause local energy deficits. Strikingly, enhancing mitochondrial transport via genetic manipulation facilitates regenerative capacity by replenishing healthy mitochondria in injured axons, thereby rescuing energy deficits. An in vivo sciatic nerve crush study further shows that enhanced mitochondrial transport in snph knockout mice accelerates axon regeneration. Understanding deficits in mitochondrial trafficking and energy supply in injured axons of mature neurons benefits development of new strategies to stimulate axon regeneration. PMID- 27268500 TI - The Developmental Basis of Stomatal Density and Flux. PMID- 27268499 TI - The diagnostic validity of clinical airway assessments for predicting difficult laryngoscopy using a grey zone approach. AB - OBJECTIVES: The diagnostic validity of clinical airway assessment tests for predicting difficult laryngoscopy in patients requiring endotracheal intubation were evaluated using receiver operating characteristic (ROC) curve analysis and a grey zone approach. METHODS: In this prospective observational study, patients were evaluated during a pre-anaesthetic visit. Predictive airway assessment tests (i.e. Modified Mallampati [MMT] classification; upper lip bite test [ULBT]; mouth opening; sternomental distance; thyromental distance [TMD]; neck circumference; neck mobility; height to thyromental distance [HT/TMD]; neck circumference-to thyromental distance [NC/TMD]) were performed on each patient and LEMON, Naguib, and MACOCHA scores were also calculated. In addition, laryngeal images were acquired and assessed for percentage of glottic opening (POGO) scores. A POGO score of zero was categorized as difficult laryngoscopy. RESULTS: The incidence of difficult laryngoscopy was 14.4% (35/243). Although seven predictive airway assessments (i.e. MMT classification, ULBT, mouth opening, HT/TMD, NC/TMD, and the LEMON and Naguib models) predicted difficult laryngoscopy by ROC analyses, a grey zone approach showed that the parameters were inconclusive in approximately 70% of patients. From all the tests, the HT/TMD ratio showed the highest sensitivity (80.0%) and ULBT had the highest specificity (95.2%). CONCLUSION: Using the grey zone approach, all predictive airway assessment tests showed large inconclusive zones which may explain previous inconsistent results in the prediction of difficult laryngoscopy. Our results suggest that the usefulness of clinical airway evaluation tests for predicting difficult laryngoscopy remains controversial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01719848). PMID- 27268501 TI - Educating Families of Children Newly Diagnosed With Cancer. AB - Parents/caregivers require specialized education in order to care for their child with a newly diagnosed cancer. Currently, no evidence-based guidelines exist to identify content essential for inclusion in patient/family education prior to a child's initial discharge home; this study used Delphi methodology to obtain multidisciplinary consensus regarding essential content amongst pediatric oncology experts from the Children's Oncology Group. Three questionnaire rounds were employed to identify essential content, evaluate the importance of the educational topics identified, and gain expert consensus regarding the final ranking of topics identified and whether or not each topic was considered mandatory for inclusion in education for newly diagnosed patients. Disease specific topics were also identified for patients with leukemia, solid tumors, and central nervous system tumors. The results of this study provide, for the first time, multidisciplinary expert consensus regarding key content essential for inclusion in discharge education for newly diagnosed pediatric oncology patients. PMID- 27268502 TI - Nursing Implications for the Management of Lymphatic Malformation in Children [Formula: see text]. AB - Lymphatic malformation (LM) is a benign congenital childhood growth that presents primarily at birth, with the remainder becoming evident by age 2 years. LM can cause devastating complications such as respiratory failure, dyspnea, dysphagia, organ compression, and nerve compression. Surgery is the preferred treatment option, although resection is not always an option due to the anatomic location of the malformation. Other treatments that have been tried with success include sclerotherapy, radiofrequency ablation, propranolol, and sirolimus. Nurses have an important role in caring for the child with LM, as with any complex disease. Nurses provide care at the bedside, education to the family, case coordination, and psychosocial support. LM is a rare disease in infancy necessitating pediatric nurses to support families through prolonged treatments and potential complications. PMID- 27268503 TI - Daily Preharvest UV-C Light Maintains the High Stilbenoid Concentration in Grapes. AB - The fact that it is possible to induce stilbenoid synthesis in grapevine (Vitis vinifera) by UV-C light allows the possibility of stimulating grapevine phytoalexin production to increase disease resistance and immunity, and subsequently to limit the use of pesticides in vineyards. UV-C light was applied daily during three days before the harvesting of table grape variety Crimson seedless to study the accumulation of stilbenoid compounds during ripeness. The E resveratrol concentration was monitored during daily preharvest UV-C light application and compared with that after a single application. Daily periodic preharvest UV-C light treatment showed a cumulative effect on grape stilbenoids. An 86-fold stilbenoid level increase (sum of E-resveratrol, E-piceatannol, epsilon-viniferin, E-piceid, isorhapontigenin, omega-viniferin, and Z-piceid) in grapes was achieved. The effects of UV-C light on stilbenoid in grape cane was also addressed for the first time. Stilbenoid oligomers such as hopeaphenol, ampelopsin A, and r-viniferin were quantified in cane samples. Quality grape parameters indicated an acceleration of ripening in UV-C samples. PMID- 27268504 TI - Western Zika Virus in Human Fetal Neural Progenitors Persists Long Term with Partial Cytopathic and Limited Immunogenic Effects. AB - The recent Zika virus (ZIKV) outbreak in the Western hemisphere is associated with severe pathology in newborns, including microcephaly and brain damage. The mechanisms underlying these outcomes are under intense investigation. Here, we show that a 2015 ZIKV isolate replicates in multiple cell types, including primary human fetal neural progenitors (hNPs). In immortalized cells, ZIKV is cytopathic and grossly rearranges endoplasmic reticulum membranes similar to other flaviviruses. In hNPs, ZIKV infection has a partial cytopathic phase characterized by cell rounding, pyknosis, and activation of caspase 3. Despite notable cell death, ZIKV did not activate a cytokine response in hNPs. This lack of cell intrinsic immunity to ZIKV is consistent with our observation that virus replication persists in hNPs for at least 28 days. These findings, supported by published fetal neuropathology, establish a proof-of-concept that neural progenitors in the developing human fetus can be direct targets of detrimental ZIKV-induced pathology. PMID- 27268506 TI - A segmentation and classification scheme for single tooth in MicroCT images based on 3D level set and k-means+. AB - Accurate classification of different anatomical structures of teeth from medical images provides crucial information for the stress analysis in dentistry. Usually, the anatomical structures of teeth are manually labeled by experienced clinical doctors, which is time consuming. However, automatic segmentation and classification is a challenging task because the anatomical structures and surroundings of the tooth in medical images are rather complex. Therefore, in this paper, we propose an effective framework which is designed to segment the tooth with a Selective Binary and Gaussian Filtering Regularized Level Set (GFRLS) method improved by fully utilizing 3 dimensional (3D) information, and classify the tooth by employing unsupervised learning i.e., k-means++ method. In order to evaluate the proposed method, the experiments are conducted on the sufficient and extensive datasets of mandibular molars. The experimental results show that our method can achieve higher accuracy and robustness compared to other three clustering methods. PMID- 27268505 TI - The IFITMs Inhibit Zika Virus Replication. AB - Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses. PMID- 27268507 TI - Pharmacogenetics of nevirapine excretion into breast milk and infants' exposure through breast milk versus postexposure prophylaxis. AB - AIM: The influence of genetic factors on nevirapine (NVP) breast milk pharmacokinetics and breastfed infants' exposure were investigated. PATIENTS & METHODS: Associations between nine SNPs in NVP disposition genes in mothers and its plasma and breast milk concentrations were explored in nursing mother-infant pairs. RESULTS: NVP pharmacokinetics in maternal plasma, breast milk and infant exposure indices were influenced by CYP2B6 516G>T and 983T>C. The median (range) milk-to-plasma area under the curve (AUC0-12) ratio was 0.95 (0.56-1.5). Calculated as percentages of pediatric treatment, infant postexposure prophylaxis and maternal weight-adjusted doses, the maximum exposure indices were 3.64% (1.99 9.88), 26.0% (9.93-79.1) and 13.8% (5.77-27.7), respectively. Infant plasma concentration as a result of exposure through breast milk (n = 93), pre-exposure prophylaxis (n = 10) and both (n = 27) were 660 (104-3090), 1020 (401-3325) and 2720 ng/ml (1360-7290), respectively. CONCLUSION: The clinical significance of the observed differences between routes of infants' exposure warrants further investigation. PMID- 27268508 TI - Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014-2015. AB - Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities. PMID- 27268509 TI - The Task and Relational Dimensions of Online Social Support. AB - Online support groups are attractive to individuals suffering from various types of mental and physical illness due to their accessibility, convenience, and comfort level. Individuals coping with depression, in particular, may seek social support online to avoid the stigma that accompanies face-to-face support groups. We explored how task and relational messages created social support in online depression support groups using Cutrona and Suhr's social support coding scheme and Bales's Interaction Process Analysis coding scheme. A content analysis revealed emotional support as the most common type of social support within the group, although the majority of messages were task rather than relational. Informational support consisted primarily of task messages, whereas network and esteem support were primarily relational messages. Specific types of task and relational messages were associated with different support types. Results indicate task messages dominated online depression support groups, suggesting the individuals who participate in these groups are interested in solving problems but may also experience emotional support when their uncertainty is reduced via task messages. PMID- 27268510 TI - Inappropriate ICD shocks do not induce pro-arrhythmic electrocardiographic changes in men. AB - OBJECTIVES: Longer-term electrocardiographic effects of multiple inappropriate ICD shocks were investigated to study their hypothesized pro-arrhythmic potential. DESIGN: Thirteen male patients with ischemic cardiomyopathy who received >=2 inappropriate shocks within 24 h and for whom 12-lead ECGs were available both before and within 72h after the inappropriate shocks were analyzed. Exclusion criteria included continuous ventricular pacing, underlying AF, events within 6 weeks after lead implantation and concomitant acute medical problems. RESULTS: A total of 149 inappropriate shocks (mean 11 +/- 19) were received. There were no significant differences in any of the measured intervals or morphological indices, nor was there a correlation between the "before-after" differences and the number of shocks received. Non-significant changes showed Percentage of Loop Area increase and relative T-wave Residuum decrease while the opposite changes have previously been associated with arrhythmic risk. CONCLUSIONS: No potentially pro-arrhythmic electrocardiographic changes were found 19 h after multiple inappropriate shocks. PMID- 27268511 TI - Extra five years of aromatase inhibitors increases disease-free survival in breast cancer. PMID- 27268512 TI - Transcriptomics-Guided Design of Synthetic Promoters for a Mammalian System. AB - Despite recent advances in improving titers for therapeutic proteins such as antibodies to the 10 g/L scale, these high yields can only be achieved in select mammalian hosts. Regardless of the host or product, strong promoters are required to obtain high levels of transgene expression. However, the promoters employed to drive this expression are rather limited in variety and are usually either viral derived or screened empirically during vector design. To begin to move away from viral parts, we employed a more systematic approach to identify and design new synthetic promoters using endogenous elements. To do so, we established a workflow to design these elements by (1) analyzing the transcriptomics profile of a specific cell line under a desired, representative cell culture condition, (2) identifying key genetic motifs using bioinformatics that can be used to rationally construct synthetic promoters, (3) building synthetic promoters using conventional DNA synthesis and molecular biology techniques, and (4) evaluating the performance of these synthetic promoters using model proteins. The resulting promoters perform comparably to the hCMV IE promoter variants tested, but with endogenous components. During this design-build-test cycle we also investigated the underlying design rules for transcription factor binding site arrangement in synthetic promoters. Overall, this approach of using an "omics-guided" workflow for designing synthetic promoters facilitates the construction of high expression vectors for immediate use in current production hosts. PMID- 27268513 TI - Effectiveness of an interprofessional workshop on pain management for medical and nursing students. AB - Interprofessional (IP) care is critical for effective pain management, but evidence is lacking about the best way to teach pain management skills to medical and nursing students using IP strategies. In 2013 and 2014, 307 medical and 169 nursing students participated in an IP case-based pain management workshop. The aims of this study were to determine (1) if students who participate in IP case based learning groups will have improved pain management skills compared to students who participate in uniprofessional case-based learning groups, and (2) if students mentored by faculty with IP training will have improved pain management skills compared to students who are not mentored by IP-trained faculty. Student learning was assessed and compared using scored checklists for each group's pain management plans. Findings show that IP mentorship and IP group participation improved medical students' pain management skills but did not have the same effect on nursing student performance. Continued work is needed to develop, refine, and integrate innovative and tailored IP strategies into the curricula of medical and nursing schools to advance the pain management competencies of students before they enter clinical practice. PMID- 27268514 TI - Local resection may be a strong alternative to cesarean hysterectomy in conservative surgical management of placenta percreta: experiences from a tertiary hospital. AB - OBJECTIVE: To evaluate and describe a surgical approach for uterine preservation and management of postpartum hemorrhage in placenta percreta. METHODS: We analyzed the data of patients who were diagnosed with placenta percreta prenatally and subsequently underwent cesarean section in which local resection technique was used to manage postpartum hemorrhage and uterine preservation at our tertiary care center between 2013 and 2016. The technique includes local resection of placental invasion site and suturing the new uterine edges. RESULTS: The technique of local resection described above was successful in preserving the uterus and stopping the bleeding in 8 of 12 cases. The diagnosis of placenta percreta in all cases was confirmed intraoperatively and postoperatively by histological examinations. Four cases were resorted to hysterectomy. The mean number of transfused erythrocyte suspension was 4.8 +/- 2.6. One complication of bladder injury was encountered in which treated conservatively. CONCLUSION: Local resection of percreta site is an effective, safe and fertility preserving approach that can be applied to manage the postpartum hemorrhage and preservation of uterus in patients with placenta percreta. PMID- 27268515 TI - Graphene Oxide-Assisted Liquid Phase Exfoliation of Graphite into Graphene for Highly Conductive Film and Electromechanical Sensors. AB - Here, we report a new method to prepare graphene from graphite by the liquid phase exfoliation process with sonication using graphene oxide (GO) as a dispersant. It was found that GO nanosheets act a as surfactant to the mediated exfoliation of graphite into a GO-adsorbed graphene complex in the aqueous solution, from which graphene was separated by an additional process. The preparation of isolated graphene from a single to a few layers is routinely achieved with an exfoliation yield of up to higher than 40% from the initial graphite material. The prepared graphene sheets showed a high quality (C/O ~ 21.5), low defect (ID/IG ~ 0.12), and high conductivity (6.2 * 10(4) S/m). Moreover, the large lateral size ranging from 5 to 10 MUm of graphene, which is believed to be due to the shielding effect of GO avoiding damage under ultrasonic jets and cavitation formed by the sonication process. The thin graphene film prepared by the spray-coating technique showed a sheet resistance of 668 Omega/sq with a transmittance of 80% at 550 nm after annealing at 350 degrees C for 3 h. The transparent electrode was even greater with the resistance only 66.02 Omega when graphene is deposited on an interdigitated electrode (1 mm gap). Finally, a flexible sensor based on a graphene spray-coating polydimethylsiloxane (PDMS) is demonstrated showing excellent performance working under human touch pressure (<10 kPa). The graphene prepared by this method has some distinct properties showing it as a promising material for applications in electronics including thin film coatings, transparent electrodes, wearable electronics, human monitoring sensors, and RFID tags. PMID- 27268516 TI - Prevalence and Predictors of Metabolic Syndrome in People With Schizophrenia in Inpatient Rehabilitation Wards. AB - BACKGROUND: Atypical antipsychotic medications increase the risk of developing metabolic syndrome (MetS) and cardiovascular diseases in people with schizophrenia. AIM: To explore the prevalence of MetS and the predictors associated with the number of MetS components in people with chronic schizophrenia. METHODS: We recruited 357 participants from 10 rehabilitation wards in northern Taiwan. The Beck Anxiety Inventory, Beck Depression Inventory II, Health-Promoting Lifestyle Profile (HPLP), and modified Baecke physical activity questionnaire were used to evaluate the participants. MetS prevalence was calculated using the modified Adult Treatment Panel III criteria for Asians. RESULTS: The prevalence of MetS in this sample was 37.8%. Multinomial logistic regression revealed that the HPLP-exercise score (odds ratio [OR] = 0.411, p = .002) and depressive symptoms (OR = 0.949, p = .040) were protective factors for >=4 MetS components. The leisure physical activity level (OR = .536, p = .024) was a protective factor for three MetS components. Body mass index >=24 kg/m(2) was the strongest risk factor for two MetS components (OR = 8.057, p < .001), three MetS components (OR = 11.287, p < .001), and >=four MetS components (OR = 15.621, p < .001). Additionally, participants' age >40 (OR = 3.638, p = .012) was a risk factor for >=four MetS components. CONCLUSION: In this study, the prevalence of MetS was higher than that reported for patients utilizing community based services in Taiwan. The important risk factors for MetS were being overweight and older than 40. The protective factors for MetS were a high HPLP exercise score and leisure-based physical activities. PMID- 27268517 TI - Static headspace-gas chromatography-mass spectrometry for the simultaneous determination of trihalomethanes and haloacetic acids in canned vegetables. AB - Canned vegetables appear to be a possible exposure pathway for hazardous disinfection by-products due to the use of sanitizers and treated water by the canning industry in the preparation of these foods. This work reports on two static headspace-gas chromatography-mass spectrometry methods for the simultaneous determination of 10 trihalomethanes (THMs) and 13 haloacetic acids (HAAs) in both solid and liquid phases of the canned vegetables. Both methods carry out the whole process (including the leaching of target analytes from the vegetable), derivatization of HAAs and volatilization of THMs and HAA esters, in a single step within a static headspace unit. The methods proposed provide an efficient and simple tool for the determination of regulated disinfection by products in canned vegetables. Average limits of detection for THMs and HAAs were 0.19 and 0.45MUg/kg, respectively, in the solid phase of canned vegetables, and 0.05 and 0.09MUg/L, respectively, in the liquid phase. Satisfactory recoveries (90-99%) and precision, calculated as relative standard deviations (RSD<=10%), were obtained in both phases of canned vegetables. The methods proposed were applied for the analysis of frequently-used canned vegetables and confirmed the presence of up to 3 THMs and 5 HAAs at microgram per kilogram or liter levels in both phases of the samples. PMID- 27268518 TI - An integrated platform for directly widely-targeted quantitative analysis of feces part I: Platform configuration and method validation. AB - Direct analysis is of great importance to understand the real chemical profile of a given sample, notably biological materials, because either chemical degradation or diverse errors and uncertainties might be resulted from sophisticated protocols. In comparison with biofluids, it is still challenging for direct analysis of solid biological samples using high performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Herein, a new analytical platform was configured by online hyphenating pressurized liquid extraction (PLE), turbulent flow chromatography (TFC), and LC-MS/MS. A facile, but robust PLE module was constructed based on the phenomenon that noticeable back-pressure can be generated during rapid fluid passing through a narrow tube. TFC column that is advantageous at extracting low molecular analytes from rushing fluid was employed to link at the outlet of the PLE module to capture constituents-of interest. An electronic 6-port/2-position valve was introduced between TFC column and LC-MS/MS to fragment each measurement into extraction and elution phases, whereas LC-MS/MS took the charge of analyte separation and monitoring. As a proof of concept, simultaneous determination of 24 endogenous substances including eighteen steroids, five eicosanoids, and one porphyrin in feces was carried out in this paper. Method validation assays demonstrated the analytical platform to be qualified for directly simultaneous measurement of diverse endogenous analytes in fecal matrices. Application of this integrated platform on homolog-focused profiling of feces is discussed in a companion paper. PMID- 27268519 TI - Rationale behind the optimum efficiency of columns packed with new 1.9MUm fully porous particles of narrow particle size distribution. AB - Columns packed with new commercially available 1.9 fully porous particles of narrow particle size distribution (nPSD) are characterized by extremely high efficiency. Under typical reversed phase conditions, these columns are able to generate very high number of theoretical plates (in the order of 300,000plates/m and more). In this paper, we investigate the origin of the high performance of these nPSD columns by performing a series of measurements that include, in addition to the traditional determination of the van Deemter curve, peak parking, pore blocking and inverse size exclusion experiments. Two nPSD columns (both 100*3.0mm) have been considered in this study: the first one, packed with particles of 80A pore size, is commercially available. The second one is a prototype column packed with 1.9 fully porous particles of 120A pore size. The main conclusion of our study is that these nPSD columns are characterized by extremely low eddy dispersion, while longitudinal diffusion and mass transfer kinetics are substantially equivalent to those of other fully porous particles of similar chemistry. PMID- 27268520 TI - Effect of the crosslinker type on the enantioseparation performance of beta cyclodextrin functionalized monoliths prepared by the one-pot approach. AB - Low column efficiency for enantioseparations in capillary liquid chromatography (CLC) is a major problem commonly encountered with beta-cyclodextrin (beta-CD) functionalized polymer-based monoliths. In order to investigate the effect of the crosslinker type on enantioseparation performance, three commonly used crosslinkers, i.e. 1,4-bis(acryloyl)piperazine (PDA), ethylene dimethacrylate (EDMA) and N,N-methylenebisacrylamide (MBA), were copolymerized using the one-pot approach with glycidyl methacrylate-mono-6-amino-6-deoxy-beta-CD (GMA-NH2-beta CD) as functional monomer. The three monolithic columns, including poly(GMA-NH2 beta-CD-co-PDA) and poly(GMA-NH2-beta-CD-co-MBA), as well as the previously reported column poly(GMA-NH2-beta-CD-co-EDMA) were systematically compared with respect to morphology, permeability, beta-CD density, retention mechanism and efficiency. The enantioseparation ability of each column was evaluated using 14 chiral compounds, including mandelic acid derivatives, profens, N-derivatized amino acids, and herbicides, as test substances. The beta-CD-functionalized monolith with MBA as crosslinker was found to exhibit higher polarity, higher column efficiency and better enantioseparation performance than those with PDA or EDMA as crosslinker. PMID- 27268521 TI - Liquid chromatography-quadrupole time of flight tandem mass spectrometry-based targeted metabolomic study for varietal discrimination of grapes according to plant sterols content. AB - Grapevine and derived products are rich in a wide range of compounds and its quality mainly depends on its metabolites, as a result of viticulture practices. Plant sterols, also called phytosterols (PS), are secondary metabolites regarded as bioactive substance present in grape berries and other plant-based food. The present study deals with a metabolomic approach focusing on phytosterols family in six varieties of Rioja grapes (Cabernet Sauvignon, Tempranillo, Graciano, Garnacha, White Garnacha and Viura), in order to find significant differences among them. Liquid chromatography- mass spectrometry with a quadrupole-time of flight mass analyzer (LC-QTOF) was used to find as many metabolites as possible in the different grape berry fractions, and using statistics to help finding significant clustering of the metabolic profile of pulp, peel and seeds in relation to the variety. The best chromatographic and detection conditions were achieved by gas phase ionization via atmospheric pressure chemical ionization (APCI) in positive mode. Furthermore, analysis with electrospray (ESI) is also needed for phytosterol derivatives confirmation. Putative compounds of interest in the analyzed samples were found by an automated compound extraction algorithm (Molecular Feature Extraction, MFE) and an initial differential expression from the data was created with the aid of commercial software. Once the data were collected, the results were filtered, aligned and normalized, and evaluating applying one-way analysis of variance (ANOVA) with a 95% significance level. For sample class prediction, partial least square-discriminant analysis (PLS-DA) is used as a supervised pattern recognition method and excellent separation among the grape varieties is shown. An overall accuracy of 93.3% (pulp samples), 100.0% (peel) or 96.7% (seeds) in discriminating between grape varieties was achieved when comparing the different fractions. In general, 7 PS derivatives were identified with ID scores higher than 84%. PMID- 27268522 TI - Versatile Route to Benzoannulated Medium-Ring Carbocycles via Aryne Insertion into Cyclic 1,3-Diketones: Application to a Synthesis of Radermachol. AB - A general approach involving the insertion of in situ generated aryne into the C C bond of cyclic 1,3-diketones for rapidly assembling functionalized benzo-fused medium ring carbocycles is delineated. The efficacy of the methodology has been demonstrated through a concise total synthesis of pentacyclic natural product radermachol. PMID- 27268523 TI - First-Principles Molecular Dynamics Studies of Organometallic Complexes and Homogeneous Catalytic Processes. AB - Computational chemistry is a valuable aid to complement experimental studies of organometallic systems and their reactivity. It allows probing mechanistic hypotheses and investigating molecular structures, shedding light on the behavior and properties of molecular assemblies at the atomic scale. When approaching a chemical problem, the computational chemist has to decide on the theoretical approach needed to describe electron/nuclear interactions and the composition of the model used to approximate the actual system. Both factors determine the reliability of the modeling study. The community dedicated much effort to developing and improving the performance and accuracy of theoretical approaches for electronic structure calculations, on which the description of (inter)atomic interactions rely. Here, the importance of the model system used in computational studies is highlighted through examples from our recent research focused on organometallic systems and homogeneous catalytic processes. We show how the inclusion of explicit solvent allows the characterization of molecular events that would otherwise not be accessible in reduced model systems (clusters). These include the stabilization of nascent charged fragments via microscopic solvation (notably, hydrogen bonding), transfer of charge (protons) between distant fragments mediated by solvent molecules, and solvent coordination to unsaturated metal centers. Furthermore, when weak interactions are involved, we show how conformational and solvation properties of organometallic complexes are also affected by the explicit inclusion of solvent molecules. Such extended model systems may be treated under periodic boundary conditions, thus removing the cluster/continuum (or vacuum) boundary, and require a statistical mechanics simulation technique to sample the accessible configurational space. First principles molecular dynamics, in which atomic forces are computed from electronic structure calculations (namely, density functional theory), is certainly the technique of choice to investigate chemical events in solution. This methodology is well established and thanks to advances in both algorithms and computational resources simulation times required for the modeling of chemical events are nowadays accessible, though the computational requirements use to be high. Specific applications reviewed here include mechanistic studies of the Shilov and Wacker processes, speciation in Pd chemistry, hydrogen bonding to metal centers, and the dynamics of agostic interactions. PMID- 27268564 TI - Efficacy of Inpatient Rehabilitation After Left Ventricular Assist Device Implantation. AB - BACKGROUND: Left ventricular assist devices (LVADs) have become an increasingly popular and effective means for treating advanced heart failure. LVAD implantation requires extensive surgery and postoperative rehabilitation. The Functional Independence Measure (FIM) has been used to quantify functional gains in numerous patient populations, including those with stroke and spinal cord injury. This study investigated functional improvements in patients undergoing LVAD implantation using the FIM score. OBJECTIVE: To assess functional improvements in patients with advanced heart failure who underwent LVAD implantation. DESIGN: Retrospective. SETTING: Inpatient rehabilitation unit. SUBJECTS: Ninety consecutive patients who received acute inpatient rehabilitation after continuous flow LVAD implantation. METHODS: Demographic, laboratory, and functional outcomes data including inpatient rehabilitation unit (IRU) length of stay (LOS), discharge disposition, and FIM score were collected for all patients. Paired t-tests were used to assess change in functional measures and laboratory data. MAIN OUTCOME MEASURES: Primary outcome measures included FIM gain, FIM efficiency, discharge disposition, rates of readmission after discharge from rehabilitation, and LOS in the rehabilitation unit. RESULTS: The FIM gain was statistically significant at 28.4 +/- 12.3 (P < .001) and compared favorably with benchmarks for mean FIM gains at our facility (26.4), regionally (21.5), and nationally (22.7) for patients admitted to IRUs with a cardiac diagnosis. FIM efficiency (FIM gain/IRU LOS) was 1.9 +/- 1.0 compared with the mean FIM efficiency at our facility (2.2), regionally (2.1), and nationally (2.2). Seventy four percent (n = 67) of patients were discharged directly home after inpatient rehabilitation, 17% (n = 16) were readmitted to the acute hospital service, and 8% (n = 7) required additional rehabilitation at a subacute rehabilitation facility. The IRU LOS was 16.2 +/- 6.9 days. CONCLUSIONS: Our study indicates that most patients with an LVAD achieve clinically meaningful functional gains from acute inpatient rehabilitation, with the majority of patients being discharged home. Further studies need to be performed to analyze clinical outcomes after acute inpatient rehabilitation. LEVEL OF EVIDENCE: IV. PMID- 27268566 TI - Do extraversion and neuroticism moderate the association between bullying victimization and internalizing symptoms? A three-wave longitudinal study. AB - The current study examined the moderating roles of neuroticism and extraversion in victims of bullying. According to a stress-diathesis model, we hypothesized that adolescents with high levels of neuroticism and low levels of extraversion would react to victimization with increased symptoms of depression and social anxiety. A sample of 1440 adolescents (648 girls and 792 boys; ages between 13- and 17-years-old) completed measures of extraversion and neuroticism at time 1, as well as measures of bullying victimization, depressive symptoms and social anxiety symptoms at time 1, time 2, and time 3 (in intervals of six months). The results of multilevel analyses for longitudinal data indicated that there was a weak association between bullying victimization and social anxiety symptoms for the adolescents who scored high on extraversion. In addition, the adolescents with high levels of extraversion presented a greater reduction in depressive symptoms over time than adolescents with low levels. Although neuroticism predicted both depression and social anxiety, no significant interactions were evident between neuroticism and bullying victimization. Regarding gender differences, the association between bullying victimization and social anxiety was stronger for boys than for girls, whereas the association between neuroticism and depression was stronger for girls. PMID- 27268565 TI - Falls and Fear of Falling After Stroke: A Case-Control Study. AB - BACKGROUND: Falls are common after stroke, with potentially serious consequences. Few investigations have included age-matched control participants to directly compare fall characteristics between older adults with and without stroke. Further, fear of falling, a significant psychological consequence of falls, has only been examined to a limited degree as a risk factor for future falls in a stroke population. OBJECTIVE: To compare the fall history between older adults with and without a previous stroke and to identify the determinants of falls and fear of falling in older stroke survivors. DESIGN: Case-control observational study. SETTING: Primary teaching hospital. PARTICIPANTS: Seventy-five patients with stroke (mean age +/- standard deviation, 66 +/- 7 years) and 50 age-matched control participants with no previous stroke were tested. METHODS: Fall history, fear of falling, and physical, cognitive, and psychological function were assessed. A chi2 test was performed to compare characteristics between groups, and logistic regression was performed to determine the risk factors for falls and fear of falling. MAIN OUTCOME MEASURES: Fall events in the past 12 months, Fall Efficacy Scale-International, Berg Balance Scale, Functional Ambulation Category, Fatigue Severity Scale, Montreal Cognitive Assessment, and Patient Healthy Questionnaire-9 were measured for all participants. Fugl-Meyer Motor Assessment was used to quantify severity of stroke motor impairments. RESULTS: Twenty-three patients and 13 control participants reported at least one fall in the past 12 months (P = .58). Nine participants with stroke had recurrent falls (>=2 falls) compared with none of the control participants (P < .01). Participants with stroke reported greater concern for falling than did nonstroke control participants (P < .01). Female gender was associated with falls in the nonstroke group, whereas falls in the stroke group were not significantly associated with any measured outcomes. Fear of falling in the stroke group was associated with functional ambulation level and balance. Functional ambulation level alone explained 22% of variance in fear of falling in the stroke group. CONCLUSIONS: Compared with persons without a stroke, patients with stroke were significantly more likely to experience recurrent falls and fear of falling. Falls in patients with stroke were not explained by any of the outcome measures used, whereas fear of falling was predicted by functional ambulation level. This study has identified potentially modifiable risk factors with which to devise future prevention strategies for falls in patients with stroke. LEVEL OF EVIDENCE: III. PMID- 27268567 TI - Teacher-student relationships and adolescent behavioral engagement and rule breaking behavior: The moderating role of dopaminergic genes. AB - This study examined whether the dopamine transporter DAT1 and the dopamine receptor DRD4 genes moderate the effect of student-reported teacher-student relationship affiliation or dissatisfaction on parent-reported adolescent rule breaking behavior and behavioral engagement. The sample included 1053 adolescents (51% boys, Mage=13.79) from grades 7 to 9. Regression analyses were conducted using Mplus while controlling for multiple testing and nested data. Adolescents who experienced stronger affiliation with their teachers were more engaged in school, whereas greater dissatisfaction predicted more rule-breaking behavior. In addition, a significant gene-environment interaction was found for both genes examined. The link between low teacher-student affiliation and low engagement was more pronounced for DAT1-10R homozygotes. The link between high teacher-student dissatisfaction and more rule-breaking was stronger for DRD4 non-long carriers. Implications for understanding the role of teacher-student relationships in adolescence and suggestions for future research are outlined. PMID- 27268568 TI - Teleconsultation: The use of technology to improve evidence-based practices in rural communities. AB - Problem-solving consultation in schools has been found to be an effective method of service delivery to support teachers who are struggling to address student social-emotional behavioral (SEB) concerns. Despite its benefits, a number of barriers (e.g., lack of time and limited access to trained professionals) restrict the use of consultation within schools, especially in rural settings. The purpose of the study was to examine the impact of teleconsultation designed to improve behavior support to students living in rural communities. Both student outcomes and teacher perceptions were evaluated. Results indicated that (a) student disruptive behaviors improved through the implementation of an individualized behavior support plan developed through teleconsultation, and (b) teachers found the teleconsultation experience acceptable and feasible. As the demands placed on psychologists and the quality of videoconferencing continue to increase, teleconsultation is becoming a viable option for service delivery within rural school settings. PMID- 27268569 TI - Classroom quality as a predictor of first graders' time in non-instructional activities and literacy achievement. AB - This study investigated how quality of the classroom learning environment influenced first grade students' (n=533) time spent in two non-instructional classroom activities (off-task and in transition) and their subsequent literacy outcomes. Hierarchical linear modeling revealed that higher classroom quality was related to higher student performance in reading comprehension and expressive vocabulary. Further, classroom quality predicted the amount of time students spent off-task and in transitions in the classroom, with slopes of change across the year particularly impacted. Mediation effects were detected in the case of expressive vocabulary such that the influence of classroom quality on students' achievement operated through students' time spent in these non-instructional activities. Results highlight the importance of overall classroom quality to how students navigate the classroom environment during learning opportunities, with subsequent literacy achievement impacted. Implications for policy and educational practices are discussed. PMID- 27268570 TI - Does psychotherapy work with school-aged youth? A meta-analytic examination of moderator variables that influence therapeutic outcomes. AB - The present study is a quantitative synthesis of the available literature to investigate the efficacy of psychotherapy for children's mental health outcomes. In particular, this study focuses on potential moderating variables-study design, treatment, client, and therapist characteristics-that may influence therapeutic outcomes for youth but have not been thoroughly accounted for in prior meta analytic studies. An electronic search of relevant databases resulted in 190 unpublished and published studies that met criteria for inclusion in the analysis. Effect sizes differed by study design. Pre-post-test designs resulted in absolute magnitudes of treatment effects ranging from |-0.02| to |-0.76| while treatment versus control group comparison designs resulted in absolute magnitudes of treatment effects ranging from |-0.14| to |-2.39|. Changes in youth outcomes larger than 20% were found, irrespective of study design, for outcomes focused on psychosomatization (29% reduction), school attendance (25% increase), and stress (48% reduction). The magnitude of changes after psychotherapy ranged from 6% (externalizing problems) to 48% (stress). Several moderator variables significantly influenced psychotherapy treatment effect sizes, including frequency and length of treatment as well as treatment format. However, results did not support the superiority of a single type of intervention for most outcomes. Implications for therapy with school-aged youth and future research are discussed. PMID- 27268571 TI - Examining the effects of adult and peer mediated goal setting and feedback interventions for writing: Two studies. AB - The current study investigated the effects of goal setting and performance feedback on Curriculum Based Measurement in Written Expression (CBM-WE). This two study investigation examined the utility of the intervention using two different delivery mechanisms. In Study 1, fourth grade students (n=114) were provided both with (a) feedback from their teachers regarding their performance on CBM-WE probes and (b) new weekly goals or no feedback and goals, once a week for a ten week intervention period. Study 2 examined the effects of this intervention with a sample of fifth grade students (n=106) when feedback and individual goals were provided by peers within their classrooms twice weekly over the course of eight weeks compared to a practice only control condition. Results in both studies indicated that students receiving the goal setting and feedback intervention performed significantly higher on production-dependent writing indices post intervention than control groups (ES=.12-.28). Implications regarding the usefulness of goal setting and feedback utilizing CBM procedures are discussed. PMID- 27268572 TI - Programming generality into a performance feedback writing intervention: A randomized controlled trial. AB - Substantial numbers of students in the United States are performing below grade level expectations in core academic areas, and these deficits are most pronounced in the area of writing. Although performance feedback procedures have been shown to produce promising short-term improvements in elementary-aged students' writing skills, evidence of maintenance and generalization of these intervention effects is limited. The purpose of this study was to examine the immediate, generalized, and sustained effects of incorporating multiple exemplar training into the performance feedback procedures of a writing intervention using a randomized controlled trial (RCT). Results indicated that although the addition of multiple exemplar training did not improve students' writing performance on measures of stimulus and response generalization, it did result in greater maintenance of intervention effects in comparison to students who received performance feedback without generality programming and students who engaged in weekly writing practice alone. PMID- 27268573 TI - The Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016 statement. AB - We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016. As a result of 2 online surveys and a 2-day meeting of experts, the SCRIBE 2016 checklist was developed, which is a set of 26 items that authors need to address when writing about single case research. This article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. We recommend that the SCRIBE 2016 is used by authors preparing manuscripts describing single-case research for publication, as well as journal reviewers and editors who are evaluating such manuscripts. SCIENTIFIC ABSTRACT: Reporting guidelines, such as the Consolidated Standards of Reporting Trials (CONSORT) Statement, improve the reporting of research in the medical literature (Turner et al., 2012). Many such guidelines exist and the CONSORT Extension to Nonpharmacological Trials (Boutron et al., 2008) provides suitable guidance for reporting between-groups intervention studies in the behavioral sciences. The CONSORT Extension for N-of-1 Trials (CENT 2015) was developed for multiple crossover trials with single individuals in the medical sciences (Shamseer et al., 2015; Vohra et al., 2015), but there is no reporting guideline in the CONSORT tradition for single-case research used in the behavioral sciences. We developed the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016 to meet this need. This Statement article describes the methodology of the development of the SCRIBE 2016, along with the outcome of 2 Delphi surveys and a consensus meeting of experts. We present the resulting 26 item SCRIBE 2016 checklist. The article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. Supplemental materials: http://dx.doi.org/10.1037/arc0000026.supp. PMID- 27268574 TI - The modulation of extracellular superoxide dismutase in the specifically enhanced cellular immune response against secondary challenge of Vibrio splendidus in Pacific oyster (Crassostrea gigas). AB - Extracellular superoxide dismutase (EcSOD) is a copper-containing glycoprotein playing an important role in antioxidant defense of living cells exposed to oxidative stress, and also participating in microorganism internalization and cell adhesion in invertebrates. EcSOD from oyster (designated CgEcSOD) had been previously reported to bind lipopolysaccharides (LPS) and act as a bridge molecule in Vibrio splendidus internalization. Its mRNA expression pattern, PAMP binding spectrum and microorganism binding capability were examined in the present study. The mRNA expression of CgEcSOD in hemocytes was significantly up regulated at the initial phase and decreased sharply at 48 h post V. splendidus stimulation. The recombinant CgEcSOD protein (rCgEcSOD) could bind LPS, PGN and poly (I:C), as well as various microorganisms including Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Vibrio anguillarum, V. splendidus, Pastoris pastoris and Yarrowia lipolytica at the presence of divalent metal ions Cu(2+). After the secondary V. splendidus stimulation, the mRNA and protein of CgEcSOD were both down-regulated significantly. The results collectively indicated that CgEcSOD could not only function in the immune recognition, but also might contribute to the immune priming of oyster by inhibiting the foreign microbe invasion through a specific down-regulation. PMID- 27268575 TI - The systematic regulation of oyster CgIL17-1 and CgIL17-5 in response to air exposure. AB - As a proinflammatory cytokine, vertebrate interleukin 17 (IL17) plays a vital role in the balance of inflammation and homeostasis, and is involved in a systemic regulation of glucose homeostasis. In the present study, a remarkable increase of glucose concentration was observed in oyster serum after 2 d air exposure, which was followed by a rapid up-regulation of CgIL17-1 and CgIL17-5. After oysters was received an injection of extra glucose, the mRNA expressions of CgIL17-1 and CgIL17-5 were also significantly up-regulated. The histopathological changes of hepatopancreas were observed after the oysters were treated by the recombinant proteins of CgIL17-1 and CgIL17-5 in vivo or subjected to air exposure. A significant decrease of GSK3beta (Glycogen synthase kinase-3beta) protein was also observed after the injection of CgIL17-1 and CgIL17-5 recombinant proteins in vivo. When the oysters with CgIL17-1 and CgIL17-5 genes knocked down were subjected to air exposure, the decline of GSK3beta concentration was slowed down and it could still be obviously detected after 7 d compared with that in the control. Meanwhile, the expression of CgDefensin and CgDFFA was inhibited, while CgIAP was up-regulated when CgIL17-1 and CgIL17-5 genes were knocked down, and the oysters exhibited higher mortality (p < 0.05) at 3 d, whereas lower at the late stage of air exposure compared with that in the controls. The results collectively suggested that once oysters were exposed to air, the synthesis of proinflammatory cytokines CgIL17-1 and CgIL17-5 was induced by the up-regulated glucose concentration in oyster serum, which would be not only a negative feedback to the high glucose concentration through mediating the regulation of GSK3beta, but also an inducer on tissue damage and immunocompetence as well as the adaptability to stresses. PMID- 27268576 TI - The medial forebrain bundle as a target for deep brain stimulation for obsessive compulsive disorder. AB - Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the medial forebrain bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale-Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico-striato-thalamo-cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease. PMID- 27268589 TI - Quantification of the indirect effects of scallop dredge fisheries on a brown crab fishery. AB - This study aimed to describe the characteristics of the by-catch of Cancer pagurus in king scallop dredges in the Isle of Man, and to determine the damage, immediate mortality and estimated mortality during fishing seasons associated with scallop dredges. Based on dredge surveys, spatial and seasonal variations were observed, with the highest number of crabs found off the west coast of the Isle of Man in the autumn when berried females crabs were most frequently caught. In general, female crabs comprised 84% of the catch. The damage levels of crabs was high with 45% of crabs recorded as crushed or dead or with severe damage, whilst 24% of crabs exhibited missing limbs. Estimates of the potential mortality associated with scallop dredging led to a lower and upper estimate of possible crab by-catch mortality of 15t and 24t respectively which represented 3.0-4.8% of the commercial landings of brown crab for the Isle of Man. Heaviest mortalities of crabs occurred in autumn to the west of the Isle of Man when female berried crabs move offshore into deeper water. The use of a temporary and spatially restricted scallop dredging closure could provide a simple solution to mitigate additional crab mortality in the event that scallop dredging increased beyond current levels in the future. PMID- 27268590 TI - Dogs Identify Agents in Third-Party Interactions on the Basis of the Observed Degree of Contingency. AB - To investigate whether dogs could recognize contingent reactivity as a marker of agents' interaction, we performed an experiment in which dogs were presented with third-party contingent events. In the perfect-contingency condition, dogs were shown an unfamiliar self-propelled agent (SPA) that performed actions corresponding to audio clips of verbal commands played by a computer. In the high but-imperfect-contingency condition, the SPA responded to the verbal commands on only two thirds of the trials; in the low-contingency condition, the SPA responded to the commands on only one third of the trials. In the test phase, the SPA approached one of two tennis balls, and then the dog was allowed to choose one of the balls. The proportion of trials on which a dog chose the object indicated by the SPA increased with the degree of contingency: Dogs chose the target object significantly above chance level only in the perfect-contingency condition. This finding suggests that dogs may use the degree of temporal contingency observed in third-party interactions as a cue to identify agents. PMID- 27268591 TI - Efficacy, safety, and dose adjustment of cyclophosphamide in lymphoma patients requiring hemodialysis. PMID- 27268592 TI - Bacteremia due to ESKAPE pathogens: An emerging problem in cancer patients. AB - BACKGROUND AND AIM: In recent years, a few of the antibiotic-resistant bacteria, known as ESKAPE pathogens, have been found responsible for serious infections. We investigated the risk factors, and impact of ESKAPE pathogens on course of blood stream infections (BSIs) in cancer patients in comparison to coagulase negative Staphylococci (CoNS). PATIENTS AND METHODS: The data of patients with ESKAPE positive blood cultures at National Cancer Institute, Cairo University were analyzed. Identification and antimicrobial susceptibility of isolates were done using Microscan Walk Away 96. RESULTS: In a 6month period, ESKAPE pathogens were isolated from non-duplicate blood cultures in 81 episodes of 72 cases of pediatric cancer patients, while CoNS were isolated from 135 blood cultures of 116 patients. The ESKAPE pathogens isolated were Enterobacter spp., methicillin resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci in 12%, 23%, 37%, 10%, 9%, and 9% of episodes, respectively. Health-care acquired infections constituted 75% of ESKAPE infections. Duration of episodes and overall mortality were significantly higher in ESKAPE BSIs when compared to CoNS (14.5+/-7.6 versus 09.9+/-6.9), and (26% versus 4%); respectively, p value <0.001. CONCLUSIONS: ESKAPE pathogens were significantly associated with higher rates of morbidity and mortality indicating the need for improving the means of prevention of these types of infections within health care premises. Microbiology laboratories have a role in defining more dangerous infections and rapid diagnostics are required in the era of resistance. PMID- 27268593 TI - New Insights into the Mycolate-Containing Compound Biosynthesis and Transport in Mycobacteria. AB - Mycolic acids are extremely-long-chain fatty acids that compose a large family of mycolate-containing compounds, major envelope lipid components and critical pathogenicity factors of Mycobacterium tuberculosis. In recent years there have been major advances in understanding their metabolic pathway. Unknown enzymes of the fatty acid synthase type II elongation system and the condensation system that builds the mycolic acid scaffold were identified. Missing links with the mycolate-containing compound biosynthesis-such as the mechanisms of transfer onto trehalose and of translocation through the inner membrane-were deciphered, while recycling processes have emerged. Beyond the more accurate picture of the biosynthesis and translocation pathways dedicated to these unique molecules, major issues that should be addressed in the future are also discussed. PMID- 27268594 TI - Navigating Identities: Subtle and Public Agency of Bicultural Gay Youth. AB - Young people who discover their sexual attraction to people of the same sex often go through a period of ambivalence or distress, especially when they grow up in an environment that condemns homosexuality. The Dutch sociopolitical context makes the expression of same-sex desires among those with non-Dutch roots even more complicated and risky, as prevailing schemes of interpretation render the two identities incompatible. This study explores the expressions of same-sex desires and identities as well as the different forms of agency of bicultural gay youth. In-depth interviews with 14 young adults reveal how young people negotiate bicultural identities in Dutch society that brings to the fore complexities in managing diverse sexual identities and strong religious and cultural affiliations in tandem. Their strategies have the effect of questioning dominant discourses and transcend the oppositional dichotomy between sexual and ethnic forms of sociocultural otherness. PMID- 27268595 TI - Endotoxin in Size-Separated Metal Working Fluid Aerosol Particles. AB - Patients with airway symptoms working in metal working industries are increasing, despite efforts to improve the environmental air surrounding the machines. Our aim was to analyse the amount of endotoxin in size-separated airborne particles of metal working fluid (MWF) aerosol, by using the personal sampler Sioutas cascade impactor, to compare filter types, and to compare the concentration of airborne endotoxin to that of the corresponding MWFs. In a pilot field study, aerosols were collected in two separate machine halls on totally 10 occasions, using glass fibre and polytetrafluoroethylene (PTFE) filters in parallel at each station. Airborne endotoxin was distributed over all size fractions. While a major part was found in the largest size fraction (72%, 2.5-10 um), up to 8% of the airborne endotoxin was detected in the smallest size fraction (<0.25 um). Comparing the efficiency of the filter types, a significantly higher median endotoxin level was found with glass fibres filters collecting the largest particle-size fraction (1.2-fold) and with PTFE filters collecting the smallest ones (5-fold). The levels of endotoxin in the size-separated airborne particle fractions correlated to those of the MWFs supporting the aerosol-generating machines. Our study indicates that a significant part of inhalable aerosols of MWFs consists of endotoxin-containing particles below the size of intact bacteria, and thus small enough to readily reach the deepest part of the lung. Combined with other chemical irritants of the MWF, exposure to MWF aerosols containing endotoxin pose a risk to respiratory health problems. PMID- 27268596 TI - Possible APJCP Loss of PubMed/MEDLINE Listing. PMID- 27268597 TI - Thailand Consensus on Helicobacter pylori Treatment 2015. AB - Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes. PMID- 27268598 TI - Endoscopic Ultrasound Staging of Upper Gastrointestinal Malignancies. AB - Since 1980, endoscopic ultrasound (EUS) has been used as an important tool for the evaluation of malignant diseases in hollow viscus and bilio-pancreas, as well as sub-epithelial tumors. The high-resolution capacity and low penetration depth of EUS make it possible to obtain highly detailed images of the gastrointestinal wall and immediate surroundings to a depth of 4-5 cm. Thus, over the past 35 years, EUS succeeded to modify management in significant number of cases and is now considered a gold standard tool for many gastrointestinal diseases, especially in the pancreatico-biliary tract, and adjuvant needle insertion now allows access to remote lesions that were difficult to reach in the past. With the growing spectrum of indications, tissue sampling for diagnostic purposes has become common. In this review, we aim to highlight the expanding spectrum of EUS indications and uses in staging of upper gastrointestinal malignancies, especially esophageal, gastric and ampullary tumors. PMID- 27268599 TI - Prognostic Scores for Predicting Recurrence in Patients with Differentiated Thyroid Cancer. AB - BACKGROUND: Differentiated thyroid cancer (DTC) is a cancer group that shares molecular and cellular origin but shows different clinical courses and prognoses. Several prognostic factors have been reported for predicting recurrence for individual patients. This literature review aimed to evaluate prognostic scores for predicting recurrence of DTC. MATERIALS AND METHODS: A search of the MEDLINE database for articles published until December 2015 was carried out using the terms "thyroid neoplasms AND (recurrent OR persistent) AND (score OR model OR nomogram) ". Studies were eligible for review if they indicated the development of prognostic scoring models, derived from a group of independent prognostic factors, in predicting disease recurrence in DTC patients. RESULTS: Of the 308 articles obtained, five were eligible for evaluation. Two scoring models were developed for DTC including both papillary and follicular carcinoma, one for papillary carcinoma, and the other two for papillary microcarcinoma. The number of patients included in the score development cohort ranged from 59 to 1,669. The number of evaluated potential prognostic factors ranged from 4 to 25. Tumor related factors were the most common factors included in the final scores, with cervical lymph node metastases being the most common. Only two studies showed internal validation of the derived score. CONCLUSIONS: There is a paucity of prognostic scores for predicting disease recurrence in patients with DTC, in particular for follicular thyroid carcinoma. Several limitations of the created scores were found. Performance of the scores has not been adequately studied. Comprehensive validation in multiple cohorts is recommended before widespread use. PMID- 27268600 TI - Call for a Computer-Aided Cancer Detection and Classification Research Initiative in Oman. AB - Cancer is a major health problem in Oman. It is reported that cancer incidence in Oman is the second highest after Saudi Arabia among Gulf Cooperation Council countries. Based on GLOBOCAN estimates, Oman is predicted to face an almost two fold increase in cancer incidence in the period 2008-2020. However, cancer research in Oman is still in its infancy. This is due to the fact that medical institutions and infrastructure that play central roles in data collection and analysis are relatively new developments in Oman. We believe the country requires an organized plan and efforts to promote local cancer research. In this paper, we discuss current research progress in cancer diagnosis using machine learning techniques to optimize computer aided cancer detection and classification (CAD). We specifically discuss CAD using two major medical data, i.e., medical imaging and microarray gene expression profiling, because medical imaging like mammography, MRI, and PET have been widely used in Oman for assisting radiologists in early cancer diagnosis and microarray data have been proven to be a reliable source for differential diagnosis. We also discuss future cancer research directions and benefits to Oman economy for entering the cancer research and treatment business as it is a multi-billion dollar industry worldwide. PMID- 27268601 TI - RECK Gene Promoter rs10814325 Polymorphism in Egyptian Patients with Hepatocellular Carcinoma on Top of Chronic Hepatitis C Viral Infection. AB - BACKGROUND: The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene that was linked to several malignancies. OBJECTIVE: To analyze any association between RECK gene rs10814325 single-nucleotide polymorphism (SNP) and HCC susceptibility along with it is association wiht various clinico-pathological and laboratory data. MATERIALS AND METHODS: RECK gene rs10814325 SNP was estimated, using real-time PCR technique, in 30 HCC patients on top of chronic HCV infection, 30 HCV related cirrhotic patients and 30 healthy controls. RESULTS: No special pattern of association could be detected on comparing the RECK gene rs10814325 genotypes(P=0.5), or alleles(P=0.49) among the studied groups. HCC patients with TT genotype had younger age (mean of 54.1+/-6.0 years vs 60.6+/-10.2 years for TC/CC genotypes, P=0.035). Abdominal distension was significantly greater in TT genotype patients (75% vs 30% of TC/CC genotypes, P=0.045). TT genotype was present in 75% of patients with lymph node metastasis. Serum GGT levels were higher in TT genotype patients [80 of (48.5-134.8) vs 40 IU/l (33-87.5) for TC/CCgenotypes], and lower limb edema was observed in 60% of TT vs 20% of TC/CCgenotypes, however, both just failed to reach significance (P=0.05 and P=0.06, respectively). CONCLUSIONS: RECK gene rs10814325 T>C could not be considered a risk factor for HCC development on top of HCV, but may be related to the disease progression and metastasis. PMID- 27268602 TI - Significance of Some Proliferation Markers and Some Prognostic Factors in Patients with Multiple Myeloma and their Impact on the Patients' Survival. AB - BACKGROUND: Multiple myeloma (MM) is influenced by genetic and micro environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6, IL10 are known to influence the growth and survival of the malignant clone. AIM: The objectives of the present study were to investigate the circulating levels of BAFF , IL-10 and IL-6 , correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on the patients' survival. MATERIALS AND METHODS: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups. Survival analysis was performed for all patients. RESULTS: Studied markers were higher in the MM patients compared to the normal control subjects. Patients' survival was improved by high serum BAFF levels. CONCLUSIONS: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM. PMID- 27268603 TI - Interleukin-6-174 Promoter Polymorphism and Susceptibility to Hepatitis B Virus Infection as a Risk Factor for Hepatocellular Carcinoma in Iran. AB - BACKGROUND: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. OBJECTIVE: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. MATERIALS AND METHODS: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. RESULTS: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. CONCLUSIONS: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women. PMID- 27268604 TI - Diverticular Disease and Colorectal Neoplasms: Association between Left Sided Diverticular Disease with Colorectal Cancers and Right Sided with Colonic Polyps. AB - BACKGROUND: Both colorectal cancer (CRC) and diverticular disease (DD) are common in the affluent West, and their prevalence is also increasing in the rest of the world with economic development. Both diseases have common epidemiologic characteristics; increasing incidence, more common with advancing age and related to specific dietary changes. However, studies of associations between the two have generated mixed results with some showing positive correlations, whilst others have shown no or negative links. Most of these studies have been from the West with study populations that were predominantly Caucasians. Here the focus was on DD and colorectal neoplasms, including CRC, in Brunei. MATERIALS AND METHODS: All patients who had undergone complete colonoscopy between 2011 and 2014 were identified and retrospectively reviewed. Patients under the age of 18 years old or had previous colonic surgeries (including previous CRC resection) were excluded. RESULTS: The total number of colonoscopies included in the study was 2,766 (mean age 53.2+/-14.8 years old, male 51.8%), of which DD, CRC and colonic polyps were detected in 17.3%, 4.7% and 28.2% respectively. The proportions of DD, polyps and CRC increased proportionally with age (<30 years, 30-49, 50-69 and >=70). Overall, there was no association between the presence of DD and CRC (3.6% vs. 5.0%, p=0.179) but there was a significant association between CRC and left sided DD (p=0.034 by trend). There were also a significant association between presence of DD and polyps (36.1% vs. 28.2%, p=0.001), in particular with right-sided and pan-DD (p=0.001 for trend). CONCLUSIONS: Our study showed that the prevalence of DD, CRC and polyps increases with age. There were significant associations between presence of left-sided DD with CRC and right-sided or pan-DD with colonic polyps. This suggests shared risk factors. Further studies are required to assess links in other countries of the Asian Pacific region. PMID- 27268605 TI - Virological Response to Conventional Interferon Therapy Combined with Ribavirin against Various HCV Genotypes in Khyber Pakhtunkhwa, Pakistan. AB - BACKGROUND: Response to antiviral therapy has been linked to different genotypes and this impacts on clinical management. Data on general responses to standard interferon (IFN) against HCV infection exists but little is known regarding HCV genotype specific responses. PURPOSE: Therefore, we attempted to determine genotype specific responses of chronic HCV patients, having different HCV genotypes, to standard IFN and ribavirin combination therapy administered for a period of six months in Kybher Pakhtunkhwa province of Pakistan. MATERIALS AND METHODS: HCV genotype was determined for all serum samples. Each patient received standard IFN combination therapy with ribavirin administered at dose of 3 MIU three times a week and 800-1200 mg/ day, respectively, for a period of six months. After completion of this therapy, PCR was performed for all course completed subjects. RESULTS: Out of total 51 selected patients the most abundant genotypes were 3a (49.0%) and 1a (21.6%) followed by 3b (9.8%), 1b (7.84%), 2a (7.84%) and untypable (3.94%). Moast responsive genotypes were 2a followed by 3a, with end of treatment responses of 77.7%, and 72.2%. Responses for 3b, 1b and untypable were 66.7%, 33.3% and 0%, respectively. CONCLUSIONS: IFN response is efficient in case of 2a and 3a genotypes while in case of untypable genotypes, further categorization is required to know about genomic sequences and to adopt some new regimes against these genotypes. PMID- 27268606 TI - Incidence of High Grade Squamous Intraepithelial Lesions in Patients with Atypical Squamous Cells of Undetermined Significance Papanicolaou Smears at Naresuan University Hospital. AB - PURPOSE: To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. MATERIALS AND METHODS: One hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. RESULTS: CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. CONCLUSIONS: Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears. PMID- 27268607 TI - Lack of Association between the CDH1 -160C>A Polymorphism and Risk of Gastrointestinal Cancer - a Meta-Analysis. AB - E-cadherin (CDH1) genetic variations alter gene transcriptional activity of epithelial cells in vitro and may cause susceptibility to various cancers. Associations of CDH1 -160C>A polymorphism with various cancers have been widely reported. However, the results are controversial and inconsistent. To derive a more accurate estimation of the relationship, a meta-analysis was performed with regard to gastrointestinal (GI) cancer risk. Eligible studies were identified through a search of PubMed database until December 2015. Associations between the CDH1 -160C>A polymorphism and GI cancer risk was considered by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 31 studies including 11,606 cases and 12,655 controls were involved in this meta-analysis. Overall, this meta-analysis showed no association between CDH1 -160C>A polymorphism and GI cancer risk (A vs. C: OR = 1.08, 95%CI = 0.98-1.18, P = 0.086;CA vs. CC: OR = 1.09, 95%CI = 0.97- 1.22, P = 0.118; AA vs. CC: OR = 1.10, 95%CI = 0.89-1.35, P = 0.356; AA vs. CC + CA: OR = 1.06, 95%CI = 0.96-1.18, P = 0.207; CA+AA vs. CC: OR = 1.01, 95%CI = 0.84-1.22, P = 0.89). In subgroup analysis, similar results were found. In conclusion, this meta-analysis has demonstrated that there is a lack of association of the CDH1-160C>A polymorphism with GI cancer susceptibility. PMID- 27268608 TI - Detection of Epstein-Barr Virus and Cytomegalovirus in Gastric Cancers in Kerman, Iran. AB - Gastric cancer (GC) is a multifactorial disease with different factors having roles in its genesis. Helicobacter pylori and Epstein-Barr virus (EBV) are known infectious agents that could contribute. In addition, there is evidence of a relationship with cytomegalovirus (CMV). Since data on CMV prevalence in gastric cancer are limited, we here evaluated the frequency of EBV and CMV in Iranian patients. Ninety paraffin blocks of GC tissues from patients in Kerman were evaluated for the presence of EBV and CMV genomes by real-time polymerase chain reaction. EBV was detected in 10 cases (11.1%) and CMV in seven. One out of 17 female patients (5.88%) and nine out of 73 male patients (12.3%) were positive for EBV, while one out of 17 female patients (5.88%) and six out of 73 male patients (8.22%) were positive for CMV. The mean age for EBV-positive patients was 60.5+/-14.9 years and the mean age for CMV-positive patients was 67.9+/ 12.3years. This study shows that the frequency of EBV-associated GC is high in Kerman. It also indicates that further studies of associations between GC and CMV are warranted, covering larger samples and populations from different areas of the world. PMID- 27268609 TI - Increased Serum Endoglin and Transforming Growth Factor beta1 mRNA Expression and Risk of Hepatocellular Carcinoma in Cirrhotic Egyptian Patients. AB - Transforming growth factor-B1 (TGF-beta1 )and its coreceptor endoglin (ENG) have been shown to contribute to hepatocellular tumor development and malignant progression. Our aim was to evaluate the serum expression levels of ENG/ TGF beta1 mRNAs and risk of hepatocellular carcinoma in cirrhotic Egyptian patients. Our study included 77 subjects. Real time polymerase chain reaction was used to evaluate the expression level of ENG and TGF-beta1mRNAs. The relative expression ratio of ENG mRNA was 0.82 (0.1 -3.2), 0.66 (0.15-5.3), 0.38(0.007-2.8) and 0.12 (0.00-0.22) and the relative expression ratio of TGF-beta1mRNA was 1.4 (0.19 6.2), 1.2 (0.22-4.3), 1.0 (0.15-4.4) and 0.6 (0.00-2.2) for cirrhotic HCC cirrhotic, HCC only and healthy control groups respectively. Increased ENG and TGF-beta1 mRNA gene expression was correlated with TNM clinical stage. The expression ratio in TNM stage III-IV 1.1 (0.07-3.2), 1.55 (0.15-6.2) was statistically significantly higher than that in stage I-II 0.47 (0.007-2.8), 1.0 (0.31-4.4) (<0.05). Our data suggested that increased ENG and TGF-beta1 gene expression may participate in hepatocarcinogenesis and increased risk of HCC in individuals with cirrhosis. Early screening for evidence of cirrhosis and consideration of ENG and TGF-beta1 as targets for therapy and treatment strategies are warranted. PMID- 27268610 TI - Lack of Association between the MiR146a Polymorphism and Susceptibility to Thai Childhood Acute Lymphoblastic Leukemia. AB - BACKGROUND: MiRNAs, small non coding RNAs, play a role in the regulation of hematopoiesis, with effects on cell growth, differentiation, and apoptosis. In addition, MiRNAs are thought to play an important role in tumorigenesis. The miR146a G>C polymorphism can lead to alteration of miR146 expression, which appears to be associated with development and progression of several cancers. This study aimed to investigate the association of the miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood acute lymphoblastic leukemia (ALL) and clinical outcomes. MATERIALS AND METHODS: Totals of 100 childhood ALL patients and 200 healthy children were studied for miR146a polymorphisms using polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP). RESULTS: The frequency of the miR146a G allele in controls was 0.40 compared with 0.38 in ALL patients. There was no association between miRNA146a (rs2910164) G>C polymorphism and susceptibility to childhood ALL (OR=1.484, 95%CI=0.712-3.093, p=0.290). Moreover, the frequencies of miR146a (rs2910164) G>C polymorphism were not associated with demographic data and clinical outcomes in ALL cases. CONCLUSIONS: The miRNA146a polymorphism was not significantly associated with susceptibility to Thai childhood ALL or any clinico-pathological variables. PMID- 27268611 TI - Clinico-Epidemiologic Patterns of Laryngeal Cancer: 5-year Results from a Regional Cancer Centre in Northeastern India. AB - PURPOSE: To determine the risk factors, clinical symptoms and patterns of spread in laryngeal cancer. MATERIALS AND METHODS: A cross sectional study was carried out in the Regional Cancer Centre, Imphal, Manipur, India. One hundred and sixteen patients with laryngeal cancer were retrospectively reviewed for epidemiological data and descriptive statistics were reported for various variables. RESULTS: Median age at presentation was 65 years and 32.8% were undernourished at presentation. The male to female ratio was 5.4:1. Heavy smoking and tobacco chewing was associated in 91.4% and 33.6% of patients respectively. Tracheostomy was required in 21.5% leading to diagnosis of laryngeal cancer. Almost all were squamous cell carcinoma with neuroendocrine and verrucous carcinoma accounting for less than 2%. Supraglottic, glottic and trans-glottic tumors were 56.9%, 36.3% and 6.9% respectively. Nodal metastases were seen in 81.8% of supraglottic cancers and 31.6% of glottic cancers with supraglottic involvement. Level II neck nodes were the commonest site followed by level III. Distant metastases (only liver) were apparent in 1.7% at presentation. Including these liver metastases, unresectable cases were limited to 6% of the patients. CONCLUSIONS: Tobacco use is implicated in almost all of the cases and the sex ratio has also decreased due to increased female smokers. The supraglottis remains the commonest site and incidence of nodal metastases is higher than in other countries. There is also a higher requirement for tracheostomy at presentation in this region. PMID- 27268612 TI - Knowledge and Attitudes of Bangkok Metropolitan Women towards HPV and Self Sampled HPV Testing. AB - BACKGROUND: To evaluate knowledge of Bangkok women regarding HPV and self-sampled HPV testing, and their attitudes towards testing. MATERIALS AND METHODS: Thai women who had lived in Bangkok for more than 5 years, aged 25-to-65 years old, were invited to join the study. Participating women were asked to a complete self questionnaire (Thai language), with literate assistance as needed. The questionnaire was divided into 3 parts: (I) demographic data, (II) knowledge and (III) attitudes towards self-sampled HPV testing. Before proceeding to Part III of the questionnaire, a 15-minute educational video of self-sampled HPV testing was presented to all participants. RESULTS: Among 2,810 women who answered the questionnaires, 33.7% reported that they did not know about HPV. The characteristic features of these women were older age (>50 years), lower income (<600 USD/month), unemployed status, and non-attendees at cervical cancer screening. Only small numbers of women (4.6%) responded that they had heard about self-sampled HPV testing. After having information, 59.6% would not use the self sampled HPV testing as a method of cervical cancer screening (non-acceptance). Factors significantly associated with the non-acceptance were older age, lower income, having no knowledge about HPV or self-collected HPV testing, a perception that the testing was unreliable and a concern that they might not be able to perform it correctly. CONCLUSIONS: Nearly half and almost all Bangkok women did not know about HPV and self-sampled HPV testing, respectively. Approximately 60% of Bangkok women refused to do the self-sampled HPV testing. Significant negative attitudes were concerns that the testing would be unreliable and a lack of confidence to perform the procedure correctly. Education about HPV and self sampled HPV testing, ease of the procedure, or the testing models may increase rate of acceptability or positive attitudes. PMID- 27268613 TI - Targeting HSP90 Gene Expression with 17-DMAG Nanoparticles in Breast Cancer Cells. AB - BACKGROUND: Dysregulation of HSP90 gene expression is known to take place in breast cancer. Here we used D,L-lactic-co-glycolic acid-polyethylene glycol-17 dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG to inhibit the expression of HSP90 gene in the T47D breast cancer cell line. The purpose was to determine whether nanoencapsulating 17DMAG improves the anti-cancer effects as compared to free 17DMAG. MATERIALS AND METHODS: The T47D breast cancer cell line was grown in RPMI 1640 supplemented with 10% FBS. Encapsulation of 17DMAG was conducted through a double emulsion method and properties of copolymers were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity was by MTT assay. After treatment of T47D cells with a given amount of drug, RNA was extracted and cDNA was synthesized. In order to assess HSP90 gene expression, real-time PCR was performed. RESULTS: Taking into account drug load, IC50 was significant decreased in nanocapsulated 17DMAG in comparison with free 17DMAG. This finding was associated with decrease of HSP90 gene expression. CONCLUSIONS: PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of HSP90 expression, at the saesm time exerting more potent cytotoxic effects. Therefore, PLGA-PEG could be a superior carrier for this type of hydrophobic agent. PMID- 27268614 TI - Psychosocial Analysis of Cancer Survivors in Rural Australia: Focus on Demographics, Quality of Life and Financial Domains. AB - BACKGROUND: Cancer treatments can have long-term physical, psychological, financial, sexual and cognitive effects that may influence the quality of life. These can vary from urban to rural areas, survival period and according to the type of cancer. We here aimed to describe demographics and psychosocial analysis of cancer survivors three to five years post-treatment in rural Australia and also assess relationships with financial stress and quality of life domains. MATERIALS AND METHODS: In this cross-sectional study, 65 participants visiting the outpatient oncology clinic were given a self-administered questionnaire. The inclusion criteria included three to five years post-treatment. Three domains were investigated using standardised and validated tools such as the Standard Quality of Life in Adult Cancer Survivors Scale (QLACS) and the Personal and Household Finances (HILDA) survey. Included were demographic parameters, quality of life, treatment information and well-being. RESULTS: There was no evidence of associations between any demographic variable and either financial stress or cancer-specific quality of life domains. Financial stress was however significantly associated with the cancer-specific quality of life domains of appearance-related concerns, family related distress, and distress related to recurrence. CONCLUSIONS: This unique study effectively points to psychosocial aspects of cancer survivors in rural regions of Australia. Although the majority of demographic characteristics were not been found to be associated with financial stress, this latter itself is significantly associated with distress related to family and cancer recurrence. This finding may be of assistance in future studies and also considering plans to fulfil unmet needs. PMID- 27268615 TI - Incidence and Mortality of Colorectal Cancer and Relationships with the Human Development Index across the World. AB - BACKGROUND: This study aimed to investigate the standardized incidence and mortality rate of colorectal cancer and its relationship with the human development index (HDI) across the world in 2012. MATERIALS AND METHODS: This ecologic study was conducted for assessment of the correlation between age specific incidence rate (ASIR) and age-specific mortality rate (ASMR) with HDI and its components. Data for SIR and SMR for every country for the year 2012 were obtained from the global cancer project. We used a bivariate method for assessment of the correlation between SIR and SMR and HDI. Statistical significance was assumed at <0.05. Statistical analyses were performed using SPSS (Version 22.0, SPSS Inc.). RESULTS: Countries with the highest SIR of colorectal cancer in the world in 2012, were Republic of Korea, Slovakia, Hungary and countries with the highest SMR were Hungary, Croatia and Slovakia. The correlation between SIR of colorectal cancer and the HDI was 0.712 (P<=0.001), with life expectancy at birth 0.513 (P<=0.001), with mean years of schooling 0.641 (P<=0.001) and with level of income per each person of the population 0.514 (P=0.013). In addition, the correlation between SMR of colorectal cancer and the HDI was 0.628 (P<=0.001), with life expectancy at birth 0.469 (P<=0.001), with mean years of schooling 0.592 (P<=0.001) and with level of income per each person of the population 0.378 (P=0.013). CONCLUSIONS: The highest SIR and SMR of colorectal cancer was in the WHO Europe region. There was a positive correlation between HDI and SIR and SMR of colorectal cancer. PMID- 27268616 TI - Technical Improvement Using a Three-Dimensional Video System for Laparoscopic Partial Nephrectomy. AB - BACKGROUND: Laparoscopic partial nephrectomy is one of the major surgical techniques for small renal masses. However, it is difficult to manage cutting and suturing procedures within acceptable time periods. To overcome this difficulty, we applied a three-dimensional (3D) video system with laparoscopic partial nephrectomy, and evaluated its utility. MATERIALS AND METHODS: We retrospectively enrolled 31 patients who underwent laparoscopic partial nephrectomy between November 2009 and June 2014. A conventional two-dimensional (2D) video system was used in 20 patients, and a 3D video system in 11. Patient characteristics and video system type (2D or 3D) were recorded, and correlations with perioperative outcomes were analyzed. RESULTS: Mean age of the patients was 55.8+/-12.4, mean body mass index was 25.7+/-3.9 kg/m2, mean tumor size was 2.0+/-0.8 cm, mean R.E.N.A.L nephrometry score was 6.9+/-1.9, and clinical stage was T1a in all patients. There were no significant differences in operative time (p=0.348), pneumoperitoneum time (p=0.322), cutting time (p=0.493), estimated blood loss (p=0.335), and Clavien grade of >II complication rate (p=0.719) between the two groups. However, warm ischemic time was significantly shorter in the 3D group than the 2D group (16.1 min vs. 21.2min, p=0.021), which resulted from short suturing time (9.1 min vs. 15.2 min, p=0.008). No open conversion occurred in either group. CONCLUSIONS: A 3D video system allows the shortening of warm ischemic time in laparoscopic partial nephrectomy and thus may be useful in improving the procedure. PMID- 27268617 TI - Knowledge and Awareness of Colorectal Cancer among Undergraduate Students at King Abdulaziz University, Jeddah, Saudi Arabia: a Survey-Based Study. AB - BACKGROUND: This study explored the knowledge and awareness about colorectal cancer (CRC) among undergraduate students of one of the leading universities in Saudi Arabia, along with the mode of information access. MATERIALS AND METHODS: The present cross-sectional study was conducted at the King Abdulaziz University, Jeddah, Saudi Arabia, among students of different faculties. The study questionnaire, containing 28 items, was adapted from surveys identified in the relevant literature. The CRC awareness questionnaire consisted of an awareness section (early CRC signs and symptoms, and risk factors) and a knowledge section. The data were analyzed using the SPSS version 21.0. RESULTS: A total of 525 undergraduate students participated in the study. The majority were females (63.0%) and approximately half (56.8%) were medical students. The majority of the students (82.3%) were aware of CRC, and 68% thought that CRC is a preventable disease. Regarding colorectal cancer screening tests, only one-third of students (33%) had actual knowledge, while the majority of the students (77.0%) thought that there are tests which help in early detection. Only 4% of the participants had a family history of CRC. The majority of the participants (84%) thought that CRC is a disease that can be cured. Almost 50-60% participants had good awareness level regarding risk factors, and signs and symptoms. Regarding knowledge, participant responses varied for family history (52%), age (59%), chronic infection of the colon (72%), obesity and lack of exercise (66%). More than one third of the students had received information material regarding CRC from their curriculum followed by social media (20.4%), and nearly 40% from other sources such as TV, hospital and mass media. Female participants had significantly better awareness in a few questions regarding CRC awareness as compared to their male counterparts. There was a significant difference observed between medical and non medical students (<0.001) in overall score of awareness and knowledge about CRC while no significant difference found in gender-wise comparison. CONCLUSIONS: Knowledge and awareness of students about CRC were not up to the mark. Medical students and female students had better knowledge in a few areas, but the overall situation is dismal. PMID- 27268618 TI - Changes in Hematological Parameters with Pegylated Interferon in Chronic Hepatitis C Virus Infected Patients. AB - The liver is one of the most common sites of cancer in the world, hepatocellular carcinoma (HCC) predominating. HCC is the sixth most common cancer and the third leading cause of cancer related death overall. Hepatitis C is a major risk factor and HCV is a rapid spreading virus which has become a problem globally, including in Pakistan. Interferon alpha therapy is used against HCV disease to regulate cell reproduction and to boost the immune system. In minute amounts interferon alpha is produced naturally by the immune system in HCV patients in response to hepatitis C virus and binds to receptors in the target cells and starts transcription of 20-30 genes due to which it develops an antiviral influence. Interferon is also administered artificially to overcome HCV disease and remove the biological effect of the virus from the infected site. The use of interferon or Peg-IFN plus Ribavirin treatment is also associated with adverse effects on body. For the current study, a convenient sample of 156 HCV positive patients of both males and females were taken. To collect blood CP and ALT, a reduction of level data and other important information were collected from the patients at regular intervals. Findings were 11.4 % in the red blood cells (RBC), 9.64 % in the total leukocyte count (WBC), 8.4 % in the hemoglobin levels (HB), 30.3 % in the platelet (Plt) count in both sexes. There was significant reduction in ALT levels due to Pegylated interferon plus ribavirin therapy. Hence strict haemotological monitoring of blood CP and ALT levels is necessary at regular intervals to reduce severe side effects which may lead to morbidity and mortality. PMID- 27268619 TI - Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India. AB - BACKGROUND: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. OBJECTIVES: To study the predispositions of HLA alleles/haplotypes with cervical cancer. MATERIALS AND METHODS: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. RESULTS: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions beta9 and beta37 and tyrosine-non tyrosine genotype combination increased the risk of cervical cancer. CONCLUSIONS: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India. PMID- 27268620 TI - The first review study on association of DNA methylation with gastric cancer in Iranian population. AB - BACKGROUND: Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Several environmental, genetic and epigenetic factors have been suggested to have a role in GC development. Epigenetic mechanisms like histone changes and promoter hyper-methylation are now being increasingly studied. Associations between methylation of many gene promoters with the risk of gastric cancer have been investigated worldwide. Such aberrant methylation may result in silencing of specific genes related to cell cycling, cell adhesion, apoptosis and DNA repair. Thus this molecular mechanism might have a key role in proliferation and migration of cancerous cells. MATERIALS AND METHODS: In this review article we included studies conducted on DNA methylation and gastric cancer in Iranian populations. Using Science direct, Pubmed/PMC, Springer, Wiley online library and SciELO databases, all published data until 31 January 2016 were gathered. We also searched Science direct data base for similar investigations around the world to make a comparison between Iran and other countries. RESULTS: By searching these databases, we found that the association between methylation of seven gene promoters and gastric cancer had been studied in Iran until 31 January 2016. These genes were p16, hLMH1, E-cadherin, CTLA4, THRbeta, mir9 and APC. Searching in science direct database also showed that 92 articles had been published around the world till January 2016. Our investigation revealed that despite the importance of GC and its high prevalence in Iran, the methylation status of only a few gene promoters has been studied so far. More studies with higher sample numbers are needed to reveal the relation of methylation status of gene promoters to gastric cancer in Iran. CONCLUSIONS: Further studies will be helpful in identifying associations of DNA methylation in candidate genes with gastric cancer risk in Iranian populations. PMID- 27268621 TI - Comparison of Diagnostic Accuracies of Serum HE-4 Levels and 3D Power Doppler Angiography Parameters between Benign Endometrial Pathologies and Endometrial Cancer. AB - PURPOSE: To study the diagnostic accuracies of serum human epididymis protein 4 (HE-4) levels, virtual organ computer-aided analysis (VOCAL) parameters and endometrial volume in endometrial cancer cases. MATERIALS AND METHODS: One hundred and seven patients (37 with endometrial cancer and 70 with benign endometrial pathology) were included in this study. VOCAL parameters and serum HE 4 levels were compared between the groups. RESULTS: Area under the curve (AUC) values were 0.702, 0.658, 0.706 for vascularization index (VI), the flow index (FI) and the vascularization flow index (VFI), respectively. A cut off value of 0.568 for VI demonstrated 70% sensitivity, 72% specificity, 56% positive predictive value (PPV) and a81% negative predictive value (NPV). A cut off value of 25.8 for showed a senitivith of 70% and a specificity of 58% with aPPV of 46% and NPV of 78%, and with a cut off value of 0.12 for VFI 70%, 69%, 54% and 81%, respectively. The area under the curve for HE-4 was 0.814. A cut off value of 458 pmol/L was predictive of malignancy with 86% sensitivity and 63% specificity. CONCLUSIONS: VOCAL parameters and serum HE-4 levels were statistically significantly higher in the endometrial cancer patients. Serum HE-4 levels provided a greater sensitivity compared to power doppler angiography for predicting malignancy or benign endometrial pathology. PMID- 27268622 TI - Incidence Trend for Non-Hodgkin Lymphoma in the North Tunisian Population, 1998 2009. AB - BACKGROUND: In 2008, non-Hodgkin lymphoma ranked tenth among other malignancies worldwide with an incidence of around 5 cases per 100,000 in both genders. The latest available rates in Tunisia are from 2006. MATERIALS AND METHODS: This study aimed to provide an update about NHL incidence for 2009 and its trend between 1998 and 2009 as well as a projection until 2024, using data from the Salah Azaiz Institute hospital registry and the Noth Tunisia cancer registry. RESULTS: In 2009, the NHL incidence in the north of Tunisia was 4.03 cases per 100,000, 4.97 for men and 3.10 for women. Diffuse large B-cell lymphoma (DLBCL) accounted for 63.2% of all NHL subtypes. Between 1998 and 2009, the overall trend showed no significant change. When we compared the trend between two periods (1998-2005 and 2005-2009), joinpoint regression showed a significant decrease of NHL incidence in the first period with an annual percentage change (APC) of -6.7% (95% CI:[-11.2%;-2%]), then the incidence significantly increased from 2005 to 2009 with an APC of 30.5% (95% CI: [16.1%; 46.6%]. The analyses of the different subtype trends showed a significant decrease in DLBCL incidence between 1998 and 2000 (APC:-21.5; 95% CI: [-31.4%;-10.2%]) then the incidence significantly increased between 2004 and 2007 (APC: 18.5; 95% CI: [3,6%;35.5%]). Joint point analysis of the age-period-cohort model projection showed a significant increase between 2002 and 2024 with an APC of 4.5% (%95 CI: [1.5%; 7.5%]). The estimated ASR for 2024 was 4.55/100 000 (95% CI: [3.37; 6.15]). CONCLUSIONS: This study revealed an overall steady trend in the incidence of NHL in northern Tunisia between 1998 and 2009. Projection showed an increase in the incidence in NHL in both genders which draw the attention to the national and worldwide burden of this malignancy. PMID- 27268623 TI - Quality Control Usage in High-Density Microarrays Reveals Differential Gene Expression Profiles in Ovarian Cancer. AB - There are several existing reports of microarray chip use for assessment of altered gene expression in different diseases. In fact, there have been over 1.5 million assays of this kind performed over the last twenty years, which have influenced clinical and translational research studies. The most commonly used DNA microarray platforms are Affymetrix GeneChip and Quality Control Software along with their GeneChip Probe Arrays. These chips are created using several quality controls to confirm the success of each assay, but their actual impact on gene expression profiles had not been previously analyzed until the appearance of several bioinformatics tools for this purpose. We here performed a data mining analysis, in this case specifically focused on ovarian cancer, as well as healthy ovarian tissue and ovarian cell lines, in order to confirm quality control results and associated variation in gene expression profiles. The microarray data used in our research were downloaded from ArrayExpress and Gene Expression Omnibus (GEO) and analyzed with Expression Console Software using RMA, MAS5 and Plier algorithms. The gene expression profiles were obtained using Partek Genomics Suite v6.6 and data were visualized using principal component analysis, heat map, and Venn diagrams. Microarray quality control analysis showed that roughly 40% of the microarray files were false negative, demonstrating over- and under-estimation of expressed genes. Additionally, we confirmed the results performing second analysis using independent samples. About 70% of the significant expressed genes were correlated in both analyses. These results demonstrate the importance of appropriate microarray processing to obtain a reliable gene expression profile. PMID- 27268624 TI - Differential Behaviour of Selenium Analogs against Anticancer Drug Induced Apoptosis of Lymphocytes in Human Peripheral Blood. AB - Sensitising cancer cells and at the same time desensitizing normal cells is a double task in cancer management. Agents which can combat the debilitating side effects of cancer therapeutics and simultaneously synergize with anticancer agents in specifically targeting cancer cells are needed. Selenium, a proven anticarcinogen, gains due importance in terms of its efficacy to combat the side effects of cancer therapy. This study is a comparative analysis of the chemoprotective effects of selenium compounds, methyl selenol (generated from organic selenomethionine (5mmol/L ; METase 40U/L)) and sodium selenite (inorganic form)(30MUM) in peripheral blood human lymphocytes exposed to cisplatin and mitomycin. Biochemical alterations occurring in many cells during apoptosis include loss of plasma membrane phospholipid asymmetry, DNA fragmentation, and activation of caspase-3. The present study demonstrated that the selenium metabolite and selenite are efficient in protecting lymphocytes undergoing DNA damage and exerted their activity by reducing caspase 3 expression. Interestingly organic methylselenol (MeSe) was found to offer more protective effects compared to inorganic selenite (SeL), by reducing the induction of apoptosis by the cytotoxic agents. This suggests that MeSe and to a lesser extent selenite might have potential for assessment in clinical trials and could be considered as strong candidates in pharmacogenomics or in the nutriprotective arena. PMID- 27268625 TI - Correlation between EGFR Expression and Radiosensitivity in Cervical Adenocarcinoma Cases. AB - BACKGROUND: Most of the cervical cancer patients, including those with cervical adenocarcinomas, come at advanced stage in the developing world so its mortality is high. Radiotherapy is one of the treatment modality for advanced stage cervical adenocarcinomas, but its efficacy depends on several prognostic factors such as the stage, histopathology, presence of organ dysfunction and expression of cellular biology markers mainly involve in cell proliferation such as the epidermal growth factor receptor (EGFR). Some research indicates that activation of EGFR in malignancy (including cervical cancer) correlates with aggressive behavior, a poor prognosis and decreasing sensitivity of radiotherapy. However, the combination between targeted therapies and radiotherapy are innovative approaches which may provide a good result. This study aimed to assess any correlation between expression of EGFR and response to radiotherapy in cervical adenocarcinoma cases. MATERIALS AND METHODS: A total of 32 women were registered in a retrospective study period January 2007 and May 2014. Paraffin blocks from these patients were processed by classical histological techniques and for immunohistochemical staining of EGFR, scoring being accomplished according to the immunoreactive scoring (IRS) of Remmele and Stegner. RESULTS: Among the studied molecular factors, there was significant correlation expression of EGFR with poor response to radiotherapy (p=0.0001). CONCLUSIONS: The result of this study showed a significant correlation between expression of EGFR and sensitivity of radiation in cervical adenocarcinoma cases. Further research is n ecessary to obtain information about new therapeutic management. PMID- 27268626 TI - Aggressive Treatment of Performance Status 1 and 2 HCC Patients Significantly Improves Survival - an Egyptian Retrospective Cohort Study of 524 Cases. AB - BACKGROUND: In the Barcelona Clinic Liver Cancer (BCLC) system, only sorafenib is suggested for HCC patients having performance status (PS) 1 or 2 even if they have treatable lesions. In the current study, we aimed to explore the outcome of using aggressive treatment for HCC patients with PS 1 and 2. MATERIALS AND METHODS: Five hundred and twenty four patients with HCC were enrolled in this study and divided into 2 groups: 404 PS 1 and 120 PS 2. Of the included 524 patients, 136 recceived non-aggressive supportive treatment and sorafenib, while 388 patients were offered aggressive treatment in the form of surgical resection, transplantation, percutaneous ablation, trans-arterial chemoembolization and/or chemoperfusion. All the patients were followed up for a period of 2 years to determine their survival. RESULTS: Most HCC patients were CHILD A and B grades (89.4% versus 85.0%, for PS1 and PS2, respectively). Patients with PS1 were significantly younger. Out of the enrolled 524 patients, 388 were offered aggressive treatment, 253 (65.2%) having their lesions fully ablated, 94 (24.2%) undergoing partial ablation and 41 patients with no ablation (10.6%). The median survival of the patients with PS 1 who were offered aggressive treatment was 20 months versus 9 months only for those who were offered supportive treatment and sorafenib (<0.001). Regarding HCC patients with PS 2, the median survivals were similarly 19.7 months versus 8.7 months only (<0.001). CONCLUSIONS: Aggressive treatment of HCC patients with PS 1 and 2 significantly improves their survival. Revising the BCLC guidelines regarding such patients is recommended. PMID- 27268627 TI - Right-Sided and Left-Sided Colon Cancers are Two Distinct Disease Entities: an Analysis of 200 Cases in Pakistan. AB - BACKGROUND: There is growing evidence that there are differences in histological and genetic characteristics along with clinical behavior between right- and left sided colon carcinomas. We have compared various parameters of the two types and assessed associations of the results with prognosis in patients in Pakistan. MATERIALS AND METHODS: We reviewed 200 cases from our institutional database; 100 cases of right-sided and 100 cases of left-sided colon cancer. Parameters including age, gender, TNM stage, histological features and clinical outcome were analyzed. RESULTS: The patients with right-sided colon cancer were significantly older as compared to their counterparts with left-sided cancer. They presented with a lumbar mass rather than symptoms of obstruction and perforation as seen in left-sided colon cancers, and the histology showed higher percentage of poorly differentiated tumors with advanced pT stage. Moreover, Crohn's-like reactions, intra tumoral lymphocyte responses and other poor prognostic factors like lymph vascular invasion and perineural invasion were more common in right-sided cancers. CONCLUSIONS: We found that right- and left-sided colon cancers are different from each other in terms of clinical presentation, histology and clinical behavior. Right-sided colon cancers are more aggressive and are associated with poorer clinical outcome as compared to left sided colon cancers in our population. PMID- 27268628 TI - Mammography Screening Uptake among Female Health Care Workers in Primary Health Care Centers in Palestine - Motivators and Barriers. AB - BACKGROUND: Early detection remains the cornerstone of breast cancer control in terms of outcome and survival. Thus far the only breast cancer screening method proven effective is mammography. The awareness of female health care workers (HCW) about breast cancer prevention is of vital importance, as their beliefs and behavior may have a major impact on other women. This study was designed to assess mammography screening uptake among female healthcare workers at primary healthcare centers, and to identify the primary motivators and barriers that affect uptake results. MATERIALS AND METHODS: A cross sectional study design was used to assess mammography screening by 299 female healthcare workers who completed a self-administered questionnaire that assessed demographics, screening uptake, motivators and barriers. RESULTS: The mean age was 46 years (within age of risk). The majority (95.1%) demonstrated adequate knowledge about breast cancer and mammography screening and 50% of the participants reported having at least one mammogram; however only 21% of them had regularly scheduled mammograms. The most frequent reported motivator was the perceived benefit that early detection of breast cancer is important for its management (89.6%), followed by the belief that mammography can detect breast cancer before its symptoms appear (84.4%). On the other hand, the most frequent barrier reported was being busy (46.7%), followed by the lack of perceived susceptibility (41.5%). CONCLUSIONS: Mammography screening was found to be sub-optimal in a population of HCW's with 50 % stating that they received a mammogram at least once, and a minority reported regular screening. There is a pressing need for educational programs aimed at removing the barriers that limit compliance with recommendations for mammography screening, and to emphasize the importance of early detection in breast cancer treatment. Ensuring the availability and accessibility of screening services, particularly for healthcare workers within their work settings are other important factors that would improve the acceptance and compliance for mammography screening programs. PMID- 27268629 TI - Profile of HER2 +ve Gastric Cancers in Brunei Darussalam. AB - BACKGROUND: Gastric cancer is the second most common gastrointestinal cancer and is still associated with significant morbidity and mortality due to late presentation and diagnosis at advanced stages. Studies have reported that a variable proportion of gastric cancer is positive for the human epidermal growth factor receptor 2 (HER2) and patients with HER2 positive (HER2 +ve) lesions can benefit from targeted therapy. This study was conducted to assess the prevalence of HER2 +ve gastric cancers in Brunei Darussalam, a developing Southeast Asian nation. MATERIALS AND METHODS: Patients were identified from the Department of Pathology registry and retrospectively reviewed. HER2 expression was assessed by immunohistochemistry and only those staining 3+ were considered positive. RESULTS: Our study included 103 cases (66 males and 37 females) with a mean age of 65.1 +/- 14.8 years old. There were 14 cases positive for HER2 (10 males and 4 females) giving a prevalence of 13.6%. The HER2 +ve cases were significantly older (70.6 +/- 19.3 years old) than the negative cases (64.2 +/- 13.8, p=0.041) and had significantly more advanced disease (stages 3 and 4, p=0.026). There were no significant differences in gender distribution, presence of intestinal metaplasia, EBV status, Helicobacter pylori status, tumor location (proximal vs. distal) and degree of tumor differentiation (all p values >0.05). CONCLUSIONS: Our study showed that 13.6% of our gastric cancers are positive for HER2, the affected patients being older and having more advanced disease at diagnosis. PMID- 27268630 TI - Ki-67 Immunostaining and its Correlation with Microvessel Density in Patients with Mutiple Myeloma. AB - PURPOSE: To compare Ki-67 index and microvessel density MVD) in multiple myeloma and non-myeloma patients and their correlation with each other and other prognostic markers. MATERIALS AND METHODS: Forty patients were enrolled in this study between 2011-2013, 30 with multiple myelomas and 10 with non-malignant disease as controls. Proliferative activity was analyzed by Ki-67 and microvessel density (MVC) was assessed by CD34 and compared between two groups. In myeloma patients, correlation between Ki-67, MVD and other prognostic factors was assessed by Pearson correlation coefficient. RESULTS: According to Durie Salmon staging criteria, 13 patients were of stage 1, 5 of stage II and 12 of stage III. Ki-67 expression showed a positive correlation with MVD (r=0.729, <0.001) and was significantly higher (<0.0001) in myeloma patients (range 35-80%, mean 60.1 %) as compared to controls (range 8-25%, mean 18.1%). MVD/mm2 was also significantly (<0.0001) higher in myeloma patients (range 62-237/mm2, mean 178.0/mm2) than controls (range 5.2-50/mm2, mean 18.3/mm2). Ki-67 and MVD, both increased progressively with increasing stage of myeloma. Ki-67 showed significant positive correlation with blood urea and lactate dehydrogenase and a significant negative correlation with serum albumin. MVD showed a significant positive correlation with blood urea, lactate dehydrogenase, serum creatinine, beta2 microglobulin and skeletal lesions. CONCLUSIONS: Ki-67 and MVD are indicators of aggressiveness and poor prognosis having significant correlation with each other and other prognostic markers of multiple myeloma. Routine assessment of these markers may help to identify high risk patients, who may benefit from with more aggressive therapy. PMID- 27268631 TI - Overweight Relation to Liver Fluke Infection among Rural Participants from 4 Districts of Nakhon Ratchasima Province, Thailand. AB - A cross-sectional survey was conducted among 730 participants from 4 rural districts of Nakhon Ratchasima province, Thailand, with a reported high incidence of liver fluke infection. This study was aimed to examine and evaluate the nutritional status in relation to Opisthorchis viverrini infection. Participants were purposive selected from Chum Phuang, Mueang Yang, Bua Yai, and Kaeng Sanam Nang districts. Stool samples were prepared by Kato Katz technique and then assessed by microscopy. Anthropometry was evaluated according to the body mass index from weight and height. Descriptive statistics and Spearman rank correlation coefficients were used to evaluate the association between the nutritional status and O. viverrini infection. Of 1.64% infected with O. viverrini the highest proportions were found in age groups >=61 and 41-50 years old, Mueang Yang district. The majorities of participants had normal weight (32.2%), followed by class II obesity (28.1%), class I obesity (21.8%), underweight (10.3%), and class III obesity (8.63%). Nutritional status with class II obesity (rS=0.639, <0.01) and class I obesity (rS=0.582, <0.05), had moderately statistical significant correlations with O. viverrini infection. Meanwhile, normal weight (rS=0.437, <0.05) and class III obesity (rS=0.384, <0.05) demonstrated lower statistical significance. These findings raise the possibility that infection with O. viverrini may contribute to fat deposition and thereby have long-term consequences on human health. Further studies are needed to better understand whether O. viverrini contributes directly to fat deposition and possible mechanisms. PMID- 27268632 TI - Determining the Optimal Dose Prescription for the Planning Target Volume with Stereotactic Body Radiotherapy for Non- Small Cell Lung Cancer Patients. AB - OBJECTIVE: The aim of this study was to determine a method of dose prescription that minimizes normal tissue irradiation outside the planning target volume (PTV) during stereotactic body radiotherapy (SBRT) for patients with non-small cell lung cancer. METHODS: Previous research and patients with typical T1 lung tumors with peripheral lesions in the lung were selected for analysis. A PTV and several organs at risk (OARs) were constructed for the dose calculated; six treatment plans employing intensity modulated radiotherapy (IMRT) were produced, in which the dose was prescribed to encompass the PTV, with the prescription isodose level (PIL) set at 50, 60, 70, 80, 90 or 95% of the isocenter dose. Additionally, four OARs around the PTV were constructed to evaluate the dose received in adjacent tissues. RESULTS: The use of higher PILs for SBRT resulted in improved sparing of OARs, with the exception of the volume of lung treated with a lower dose. CONCLUSIONS: The use of lower PILs is likely to create significant inhomogeneity of the dose delivered to the target, which may be beneficial for the control of tumors with poor conformity indices. PMID- 27268633 TI - Distribution and Characteristics of Pulmonary Neuroendocrine Tumors: Single Institution Experience in Lebanon. AB - BACKGROUND: Neuroendocrine tumors represent 20% of primary lung neoplasms in some registries. According to the WHO classification of 2004, reconsidered for 2015, these lung tumors are divided into 4 groups: typical and atypical carcinoid, small cell and large cell neuroendocrine carcinomas. We report in this paper, for the first time in Lebanon, the distribution and the population characteristics of these tumors. MATERIALS AND METHODS: This descriptive retrospective study concerned all the pulmonary neuroendocrine tumors (NET) with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, with attention to features like age, gender and subgroup. RESULTS: Of 194 patients with pulmonary NET, 12.4% were typical carcinoid tumors, 3.6% atypical carcinoid, 66.5% small cell lung cancer, 7.7% combined small cell carcinomas and 9.8% large cell neuroendocrine tumors. The mean ages of patients were respectively 51.2 years in typical carcinoid, 64 years in atypical carcinoid, 64.2 years in small cell lung cancers, 67.2 in combined small cell lung cancer and 66.9 in large cells neuroendocrine tumors. The M/F sex ratios were respectively 0.3, 1.3, 1.4, 2.7 and 2.2. CONCLUSIONS: The characteristics of lung neuroendocrine tumors in our Lebanese institution are comparable to those reported in the literature. PMID- 27268634 TI - Thalidomide Combined with Chemotherapy in Treating Patients with Advanced lung Cancer. AB - OBJECTIVES: To evaluate efficacy and toxicity in patients with advanced lung cancer, including non-small cell and small cell variants (NSCLC and SCLC), treated with thalidomide plus chemotherapy. METHODS: Fourteen patients with advanced lung cancer were scheduled to receive chemotherapy combined with thalidomide. All patients in this study received thalidomide (100 mg orally per night before sleeping, produced by Changzhou Pharmaceutical Factory Co.Ltd) after the start of chemotherapy for at least 14 days. Chemotherapy was administered according to the condition of patients. After at least 14 days of treatment, efficacy and toxicity were evaluated. RESULTS: There were 6 female and 8 male patients with advanced lung cancer recruited into this study, including 2 with SCLC and 12 with NSCLC. The median age was 56.7 (44-65) years. Progressive disease was observed in 12 patients (12/14), and stable disease in 2 (2/14). Grade 1 to 2 myelosuppression was observed in 4/14 patients, and Grade 1 to 2 elevation of hepatic enzymes was recorded in 5/14 patients. Adverse effects on the gastrointestinal tract were documented in 2/14 patients, all beingGrade 1. No Grade 3-4 toxicity was recorded. No treatment related deaths occurred. CONCLUSIONS: Our results demonstrate that thalidomide combined with chemotherapy is mildly effective and safe for treating patients with advanced lung cancer. However, further evaluation of this combination is warranted. PMID- 27268635 TI - Sporadic Early Onset Colorectal Cancer in Pakistan: a Case- Control Analysis of Microsatellite Instability. AB - BACKGROUND: Early onset sporadic colorectal cancer (CRC) is a biologically and clinically distinct entity hypothesized to exhibit differences in histological features and microsatellite instability (MSI) as compared to typical onset CRC. This study compared the MSI status, mismatch repair enzyme deficiency and clinicopathological features of early onset (aged <=45 years) with controls (>45 years). MATERIALS AND METHODS: A total of 30 cases and 30 controls were analyzed for MSI status using the Bethesda marker panel. Using antibodies against hMLH1, hMSH2 and hMSH6, mismatch repair protein expression was assessed by immunohistochemistry. Molecular characteristics were correlated with clinicopathological features. RESULTS: The early onset sporadic CRCs were significantly more poorly differentiated tumors, with higher N2 nodal involvement and greater frequency of signet ring phenotype than the typical onset cases. MSI was observed in 18/30 cases, with 12/18 designated as MSI-high (MSI-H) and 6/18 designated as MSI-low (MSI-L). In the control group, 14 patients exhibited MSI, with 7 MSI-H and 7 MSI-L. MSI tumors in both cases and controls exhibited loss of hMLH1, hMSH2 and hMSH6. MSS tumors did not exhibit loss of expression of MMR proteins, except hMLH1 protein in 3 controls. No statistically significant difference was noted in MSI status or expression of MMR proteins in cases versus controls. CONCLUSIONS: Microsatellite status is comparable between early and typical onset sporadic CRC patients in Pakistan suggesting that differences in clinicopathological features between these two subsets are attributable to other molecular mechanisms. PMID- 27268636 TI - Breast Cancer in Men: a Report from the Department of Radiation Oncology in Kermanshah Province, Iran. AB - BACKGROUND: Male breast cancer (MBC) is a rare disease that accounts for less than 1% of all cancers in men and less than 1% of all diagnosed breast cancers. In this study, we retrospectively evaluated the clinicopathological features, treatment options and overall survival in Kurdish MBC cases. MATERIALS AND METHODS: Seventeen MBC were referred to Department of Radiation Oncology in Imam Reza Hospital, Kermanshah, Iran, between 2010 and 2016. Immunohistochemical analysis was performed for ER, PR and Her2 biomarkers and FISH for those with Her2 2+. Median follow-up period was 30 months (2-65 months). We excluded from the study patients who did not have follow-up after initial diagnosis. Treatment methods were chemotherapy, radiotherapy, hormonal therapy, target therapy and palliative care. Survival was estimated by the Kaplan Meier method (Prism 5). RESULTS: The mean age at diagnosis was 49.2 +/- 17 years (range, 24-85 years). Grade II was the most grade in MBC (65%). Fourteen patients (82%) had invasive ductal carcinoma, one (6%) had ductal carcinoma in situ and 2 (12%) had invasive papillary. ER, PR and Her2 were significantly positive in 14/17, 8/17 and 2/17 cases, respectively. The treatment included modified radical mastectomy for most patients. Chemotherapy with TAC and CEF regimens was delivered to 15/17 cases. Tamoxifen therapy was delivered to 14/17 cases. Three stage IV patients received Avestin and two with Her2 3+ were given Trastuzumab (Herceptin). Patients received adjuvant radiotherapy following surgery and chemotherapy. The site of metastasis was the bone in 2 cases, lung in 1 case and liver in 1 case. Zoledronic acid (Zometa) was prescribed for patients with bone metastasis. Five year overall survival rate was 64%. CONCLUSIONS: MBC is rare. Thus, we need larger studies are in collaboration with several research centers in the field of breast cancer. ER positive, grade II of invasive ductal carcinoma, stage II and right side happened more with MBC. Overall survival is similar to other studies. PMID- 27268637 TI - MMP3 in Comparison to CA 125, HE4 and the ROMA Algorithm in Differentiation of Ovarian Tumors. AB - Ovarian cancer is a highly malignant neoplasm with high mortality rates. Research to identify markers facilitating early detection has been pursued for many years. Currently, diagnosis is based on the CA 125 and HE4 markers, as well as the ROMA algorithm. The search continues for new proteins that meet the criteria of good markers A total of 90 patients were included in the present study, allocated into: group 1, ovarian cancer, with 29 patients; group 2, endometrial cysts, with 30s; and group 3, simple ovarian cysts, with 31. Following histopathological verification, the CA 125, HE4, and metalloproteinase 3 (MMP3) levels were determined and the ROMA algorithm was calculated for all patients. The mean concentrations of all determined proteins, CA 125, HE4, and MMP3, as well as the ROMA values, were significantly higher in group 1 (ovarian cancer) compared to group 3 (simple ovarian cysts). The highest significant differences for the CA 125 levels (<0.000001) and ROMA (<0.000001) values were observed in postmenopausal women. For HE4, statistical significance was at the level of p=0.00001 compared to p=0.002 for MMP3. For the differentiation between ovarian cancer and endometrial cysts, the respective AUC ratios were obtained for CA 125, HE4, and MMP3 levels, as well as the ROMA values ( 0,93 / 0,96 / 0,75 / 0,98). After removing the post-menopausal patients, the MMP3 AUC value for ovarian cancer vs. benign ovarian cysts increased to 0.814. For post-menopausal women, the MMP3 AUC value for ovarian cancer vs. endometrial cysts was 0.843. As suggested by the results above, both the CA 125 and HE4 markers, as well as the ROMA algorithm, meet the criteria of a good diagnostic test for ovarian cancer. MMP3 seems to meet the criteria of a good diagnostic test, particularly in postmenopausal women; however, it is not superior to the tests used to date. PMID- 27268638 TI - Robust Reference Intervals for Serum Kappa and Lambda Free Light Chains from a Multi Centre Study Population from Hyderabad, India: Myeloma Diagnostic Implications. AB - The International Myeloma Working Group considers the serum free light chain (SFLC) assay to be an adjunct to traditional tests. Apart from the FLC ratio, the absolute values of individual free light chains also are gaining importance as they appear to be more relevant in certain clinical settings. Automated assays are available for their determination. As laboratories put new test systems into use catering to different disease populations, they are required by accreditation and certification bodies to verify or establish performance specifications, including reference intervals (RIs) representative of their population. Our aim was to establish local RIs for SFLC in a multicentre representative healthy population using a robust method. There was no significant relationship between SFLC levels and age, gender and creatinine levels. The 95% RI for kappaSFLC was 4.81 to 33.86mg/L, for ? SFLC was 5.19 to 23.67mg/L and for kappa/?SFLC was 0.36 to 2.33, significantly higher than the values given by the manufacturer. The kappa/? SFLC ratio at 2.23, covering 100% of the data, showed 72% sensitivity (95% CI=39.0 - 94.0), 100% specificity (95% CI=71.5 - 100.0), 100% PPV (95% CI=21.5 - 100.0), 95% NPV (95% CI=75.4 - 99.9), and 79% accuracy (95% CI=56.0 - 93.0). In the patient group, kit RI for kappa /? SFLC ratio classified 45.5% (n=5) as positive vs 9.1% (n=1) positive by the study RI, while the kit RI for kappa FLC classified 90.9% (n=10) as positive vs 54.5% (n=6) , indicating increased probability of false positive test results with the kit RI when applied to our patient population. Appropriate and specific reference intervals and criteria values result in fewer false-positive and false-negative results which means fewer wrong or missed diagnoses. PMID- 27268639 TI - Prescription, Transcription and Administration Errors in Out- Patient Day Care Unit of a Regional Cancer Centre in South India. AB - BACKGROUND: Medication errors are common but most often preventable events in any health care setup. Studies on medication errors involving chemotherapeutic drugs are limited. OBJECTIVE: We studied three aspects of medication errors - prescription, transcription and administration errors in 500 cancer patients who received ambulatory cancer chemotherapy at a resource limited setting government hospital attached cancer centre in South India. The frequency of medication errors, their types and the possible reasons for their occurrence were analysed. DESIGN AND METHODS: Cross-sectional study using direct observation and chart review in anmbulatory day care unit of a Regional Cancer Centre in South India. Prescription charts of 500 patients during a three month time period were studied and errors analysed. Transcription errors were estimated from the nurses records for these 500 patients who were prescribed anticancer medications or premedication to be administered in the day care centre, direct observations were made during drug administration and administration errors analysed. Medical oncologists prescribing anticancer medications and nurses administering medications also participated. RESULTS: A total of 500 patient observations were made and 41.6% medication errors were detected. Among the total observed errors, 114 (54.8%) were prescription errors, 51(24.5%) were transcribing errors and 43 (20.7%) were administration errors. The majority of the prescription errors were due to missing information (45.5%) and administration errors were mainly due to errors in drug reconstitution (55.8%). There were no life threatening events during the observation period since most of the errors were either intercepted before reaching the patient or were trivial. CONCLUSIONS: A high rate of potentially harmful medication errors were intercepted at the ambulatory day care unit of our regional cancer centre. Suggestions have been made to reduce errors in the future by adoption of computerised prescriptions and periodic sensitisation of the responsible health personnel. PMID- 27268640 TI - Arabic Tools for Assessment of Multidimensions of Pain and Discomfort Related to Cancer. AB - BACKGROUND: Cancer is a worldwide health problem. Arabic countries are also concerned and the burden linked to the pain related to cancer is dsiquieting. The aim of this study is to set the panel of valid tools for assessing the multiple dimensions of pain in arabic speaking countries. MATERIALS AND METHODS: A systematic review on PubMed, Scopus, and Science Direct databases was conducted using as key words cancer, pain and arabic speaking population. The content of 51 articles was studied and nine articles were retained for their relevance for the issue. RESULTS: We founf eight different questionnaires. MSAS-Leb, EORTC-C30, EORTC- BR23, MDASI, FLIC, and COOP/WONCA are dedicated to physical and psychological dimensions of pain. BPI is centered on direct items for measuring pain accurately. ABQ-II is the unique tool focusing on barriers to cancer pain control. All tools are confirmed valid and reliable in the context studied for assessing pain and disconfort linked to cancer. CONCLUSIONS: This panel of questionnaires covers all relevant aims for assessing pain in diferent arabic speaking countries with the recommendation of a cultural adaptation to local arabic languages. PMID- 27268641 TI - No Association of the rs17822931 Polymorphism in ABCC11 with Breast Cancer Risk in Koreans. AB - ABCC11 is reported to be associated with breast cancer. However, whether ABCC11 polymorphisms relate to breast cancer risk remains unclear. This study aimed to evaluate any association of a single nucleotide polymorphism (SNP), rs17822931, in ABCC11 with breast cancer in Koreans. Genomic DNA samples of 170 women with breast cancer and 100 controls were assessed for SNP rs17822931 of ABCC11 by single-strand conformation polymorphism (SSCP) and DNA sequencing. A 27-bp deletion (Delta27) of ABCC11 was analyzed by PCR amplification. The genotype of SNP rs17822931 was confirmed to be AA in all samples from breast cancer patients and Delta27 was found in none of the samples. Our finding indicated that the SNP rs17822931 in ABCC11 is not associated with breast cancer. However, this study does provide information on fundamental genetic aspects of ABCC11 with regard to breast cancer risk in Koreans. PMID- 27268642 TI - Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta analysis of 7,281 Prostate Cancer Cases and 9,082 Healthy Controls. AB - Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34 studies with 7,281 cases and 9,082 controls was analyzed using STATA and MedCalc software. Overall, GSTM1 deletion (OR 3.67; CI 1.39-9.85; P= 0.001) was strongly associated with prostatic cancer. In the sub group analysis GSTM1 null deletion was also significantly associated with prostate cancer among Asians (OR 4.84; CI 1.08 21.5; P= 0.03), Eurasians (OR 17.69; CI 9.87-31.70; <0.001) and Americans (OR 0.11; CI 0.01-1.06; P= 0.05). No association was observed among Europeans (P=0.42) and Africans (P= 0.40). As a whole GSTT1 null deletion (OR 0.85; CI 0.28 2.58; P= 0.77) did not show anyt significant association with prostate cancer risk among different populations. When the data were stratified into different groups, however, Africans demonstrated a significant association of GSTT1 null deletion (OR 1.95; CI 1.57-2.39; <0.001) with prostate cancer, whereas no association was found among Asians (P= 0.90), Americans (P= 0.50), Europeans (P= 0.89) and Eurasians (P= 1.0). In conclusion, both GSTM1 and GSTT1 may contribute to prostate cancer development but GSTM1 may prove to be a stronger candidate risk factor. PMID- 27268643 TI - Combination of Nimbolide and TNF-alpha-Increases Human Colon Adenocarcinoma Cell Death through JNK-mediated DR5 Up- regulation. AB - Tumor necrosis factor (TNF-alpha), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of TNF-alpha are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on TNF-alpha-induced apoptosis in human colon adenocarcinoma (HT-29) cells. Nimbolide from Azadirachta indica was evaluated for cytotoxicity by methyl tetrazolium 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay and phase contrast microscopy. Effects on apoptotic signaling proteins were investigated using Western blot analysis. Nimbolide showed cytotoxicity against HT-29 cells that was significantly different from the control group (<0.01), a concentration of 10 MUM significantly inducing cell death (<0.01). In combination with TNF-alpha, nimbolide significantly enhanced-induced cell death. In apoptotic pathway, nimbolide activated c-Jun N-terminal kinase (JNK) phosphorylation, BH3 interacting-domain death agonist (Bid) and up-regulated the death receptor 5 (DR5) level. In the combination group, nimbolide markedly sensitized TNF-alpha induced JNK, Bid, caspase-3 activation and the up-regulation of DR5. Our findings overall indicate that nimbolide may enhance TNF-alpha-mediated cellular proliferation inhibition through increasing cell apoptosis of HT-29 cells by up reglation of DR5 expression via the JNK pathway. PMID- 27268644 TI - High-Sensitivity C-Reactive Protein and Risks of All-Cause and Cause-Specific Mortality in a Japanese Population. AB - BACKGROUND: High-sensitivity C-reactive protein (hsCRP) levels are lower in Japanese compared with Western subjects. Since it is uncertain whether hsCRP is a potent predictor of mortality at low CRP concentrations, the present study examined associations with all-cause and cause-specific mortality in a large population of Japanese. MATERIALS AND METHODS: Subjects were 4,737 men and 6,343 women aged 49-76 years participating in the baseline survey of an ongoing cohort study of lifestyle-related diseases between February 2004 and July 2006. Hazard ratios for all-cause and cause-specific mortality associated with hsCRP levels were estimated using Cox proportional hazards regression. RESULTS: A total of 436 all-cause deaths occurred during a median follow- up of 8 years. The main cause of death was cancer. In men, hsCRP levels were positively associated with the risk of all-cause mortality as well as deaths from cancer and cardiovascular disease (CVD). All-cause mortality hazards for the 2nd (0.34-0.84 mg/L) and the 3rd (>= 0.85 mg/L) tertiles of hsCRP were 1.27 (95% confidence interval [CI], 0.93-1.73) and 1.75 (1.30-2.37), respectively (p for trend=0.001). In women, increased risk of all- cause and cause-specific mortality associated with elevated hsCRP levels was observed, but the associations were not statistically significant. CONCLUSIONS: HsCRP may be an independent predictor of all-cause, cancer and CVD mortality in apparently healthy Japanese men, but not women. The differential effect of hsCRP in predicting mortality risk by sex warrants further investigation. PMID- 27268645 TI - Prevalence of IDH1/2 Mutations in Different Subtypes of Glioma in the North-East Population of Morocco. AB - BACKGROUND: Genetic alterations in gliomas have increasing importance for classification purposes. Thus, we are especially interested in studying IDH mutations which may feature potential roles in diagnosis, prognosis and response to treatment. Our aim was to investigate IDH mutations in diffuse glioma patients diagnosed in university hospital centre of Fez in Morocco. MATERIALS AND METHODS: IDH1 codon 132 and IDH2 codon 172 were direct-sequenced in 117 diffuse glioma samples diagnosed and treated in University Hospital Hassan II between 2010 and 2014. RESULTS: The R132H IDH1 mutation was identified in 43/117 tumor samples and R172K IDH2 mutation was detected in only one anaplastic oligodendroglioma. IDH mutations were observed in 63.2% of astrocytomas, 73.3% of diffuse oligodendrogliomas and 12.90% of glioblastomas. CONCLUSIONS: Our results confirmed other studies published earlier for other populations with some small discrepancies. PMID- 27268646 TI - Prognostic Factors of Prostate Cancer in Tunisian Men: Immunohistochemical Study. AB - BACKGROUND: Prostate cancer is the second most common male cancer and remains a leading cause of cancer death worldwide. Heterogeneity regarding recurrence, tumor progression and therapeutic response reflects the inadequacy of traditional prognostic factors and underlies interest in new genetic and molecular markers. In this work, we studied the prognostic value of the expression of 9 proteins, Ki 67, p53, Bcl-2, PSA, HER2, E-cadherin, p21WAF1/Cip1, p27Kip1 and p16ink4a in prostate cancer. MATERIALS AND METHODS: We conducted a retrospective study of 50 prostate cancers diagnosed in Pathology Department of Farhet Hached Hospital, Sousse, Tunisia, during a period of 12 months. Clinico-pathological data and survival were investigated. Protein expression was analyzed by immunohistochemistry on archived material. RESULTS: Expression or over-expression of Ki-67, p53, Bcl-2, PSA, HER2, E-Cadherin, p21WAF1/Cip1, p27Kip1 and p16ink4a was observed in 68%, 24%, 32%, 78%, 12%, 90%, 20%, 44% and 56% of cases, respectively. Overall five-year survival was 68%. A statistically significant correlation was observed between death occurrence and advanced age (p=0.018), degree of tumor differentiation (p=0.0001), perineural invasion (p=0.016) and metastasis occurrence (p=0.05). Death occurrence was significantly correlated with the expression of p53 (p=0.007), Bcl-2 (p=0.02), Ki-67 (p=0.05) and p27Kip1 (p=0.04). CONCLUSIONS: The p53, Bcl-2, Ki-67 and p27Kip1 proteins may be useful additional prognostic markers for prostate cancer. The use of these proteins in clinical practice can improve prognosis prediction, disease screening and treatment response of prostatic cancer. PMID- 27268647 TI - Comparative Evaluation of Silibinin Effects on Cell Cycling and Apoptosis in Human Breast Cancer MCF-7 and T47D Cell Lines. AB - Silibinin is a natural polyphenol with high antioxidant and anticancer properties. In this study, its influence on two of the most commonly employed human breast cancer cell lines, MCF-7 and T47D, and one non-malignant MCF-10A cell line, were investigated and compared. Cell viability, the cell cycle distribution and apoptosis induction were analyzed by MTT and flow cytometry, respectively. The effect of silibinin on PTEN, Bcl-2, P21, and P27 mRNAs expression was also investigated by real-time RT-PCR. It was found that silibinin caused G1 cell cycle arrest in MCF-7 and MCF-10A cells but had no effect on the T47D cell cycle. Silibinin induced cytotoxic and apoptotic effects in T47D cells more than the MCF-7 cells and had no cytotoxic effect in MCF-10A cells under the same conditions. Silibinin upregulated PTEN in MCF-7 and caused slightly increased P21 mRNA expression in T47D cells and slightly increased PTEN and P21 expression in MCF-10A cells. Bcl-2 expression decreased in all of the examined cells under silibinin treatment. P27 mRNA expression upregulated in T47D and MCF 10A cells under silibinin treatment. PTEN mRNA in T47D and P21 and P27 mRNAsin MCF-7 were not affected by silibinin. These results suggest that silibinin has mostly different inhibitory effects in breast cancer cells and might be an effective anticancer agent for some cells linked to influence on cell cycle progression. PMID- 27268649 TI - Ultrasound Breast Elastographic Evaluation of Mass-Forming Ductal Carcinoma-in situ with Histological Correlation - New Findings for a Toothpaste Sign. AB - BACKGROUND: It is unclear as to whether the size ratio elastographic technique is useful for assessing ultrasound- detected ductal carcinoma-in-situ (DCIS) masses since they commonly lack a significant desmoplastic reaction. The objectives of this study were to determine the accuracy of this elastographic technique in DCIS and examine if there was any histopathological correlation with the grey-scale strain patterns. MATERIALS AND METHODS: Female patients referred to the radiology department for image-guided breast biopsy were prospectively evaluated by ultrasound elastography prior to biopsy. Histological diagnosis was the gold standard. An elastographic size ratio of more than 1.1 was considered malignant. Elastographic strain patterns were assessed for correlation with the DCIS histological architectural patterns and nuclear grade. RESULTS: There were 30 DCIS cases. Elastographic sensitivity for detection of malignancy was 86.7% (26/30). 10/30 (33.3%) DCIS masses demonstrated predominantly white elastographic strain patterns while 20/30 (66.7%) were predominantly black. There were 3 (10.0%) DCIS masses that showed had a co-existent bull's-eye sign and 7 (23.3%) other masses had a co-existent toothpaste sign, a strain pattern that has never been reported in the literature. Four out of 4/5 comedo DCIS showed a predominantly white strain pattern (p=0.031) while 6/7 cases with the toothpaste sign were papillary DCIS (p=0.031). There was no relationship between the strain pattern and the DCIS nuclear grade. CONCLUSIONS: The size ratio elastographic technique was found to be very sensitive for ultrasound-detected DCIS masses. While the elastographic grey-scale strain pattern should not be used for diagnostic purposes, it correlated well with the DCIS architecture. PMID- 27268648 TI - Distribution of High Risk Human Papillomavirus Types in Western Kazakhstan - Retrospective Analysis of PCR Data. AB - BACKGROUND: Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Cancer of the cervix is the third or even the second most common cancer in women worldwide, more than 85% of the cases occurring in developing countries, such as China and India, including the Republic of Kazakhstan. The purpose was to determine the HPV type distribution to evaluate efficacy of vaccination and adjust cancer prevention strategy in Western Kazakhstan in the future. MATERIALS AND METHODS: A retrospective analysis was conducted of data obtained from PCR laboratories in 4 regional centers for the time period covering 12 months, 2013-2014, using AmpliSens(r) Real-Time PCR kits for HPV testing of 12 genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59). RESULTS: A total of 1,661 persons were HPV tested within 2013-14, but a proprotion examined for 16 and 18 genotypes only (563) was not been included for statistic analysis of distribution and ratio of the most common genotypes. Males accounted for only a small number (N=90 in total). CONCLUSIONS: Total number of the HPV-positive appeared to be 26.0%, or 286 of N=1098. Types distribution was as follows: type 16 (10.7%), 39 (5.83%), 51 (5.27%), 31 (4.85%), 56 (4.58%), 18 (3.61%), 59 (2.64%), 58 (2.22%), 35 (1.94%), 33 (1.25%). Overall the HPV infection was highest in 16-29 years old (62.4%) and decreased with age. Total prevalence of the HR-HPVs amongst male population was 21.4% with top five types 16, 18, 39, 51, 31. Trends forcorrelations between Aktau site and type 33 (Cramer's V 0.2029), between Caucasian ethnicity and type 33 (Cramer's V .1716), and between European ethnicities in Uralsk and type 45 (Cramer's V .1752) were found. Of N 563 tested separately for 16 or 18 types, 13.6% were positive. As a whole, the distribution of 16/18 types had a ratio of 3.53:1. Given the vaccine-targeted type 16 is widely spread amongst this regional population, HPV immunization program of adolescent girls 10-13 years should be implemented appropriately. PMID- 27268650 TI - Digestive Neuroendocrine Tumor Distribution and Characteristics According to the 2010 WHO Classification: a Single Institution Experience in Lebanon. AB - BACKGROUND: Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NEN) are relatively rare tumors, not equally distributed in the gastrointestinal system. In 2010, a revised version of the WHO classification of GEP-NENs was published. This study reports for the first time the distribution and characteristics of GEP NENs in a Lebanese population. MATERIALS AND METHODS: This descriptive retrospective study concerns all the digestive neuroendocrine tumors with their characteristics diagnosed in Hotel Dieu de France in Beirut, Lebanon from 2001 to 2012, all the pathology reports being reanalyzed according to the latest WHO 2010 classification. The characteristics and features of GEP-NEN analyzed in this study were age, gender, grade and site. RESULTS: A total of 89 GEP-NENs were diagnosed, representing 28.2% of all neuroendocrine tumors. The mean age of GEP NEN patients was 58.7 years and the M/F sex ratio was 1.2. The primary localization was as follows: 21.3%(19) pancreatic, 18% (16) gastric, 15.7% (14) duodenal, 11.2% (10) appendix, 10.1% (9) intestinal, 10.1% (9) colorectal (7.9% colonic and 2.2% rectal), 5.6% (4) hepatic, 2.2% (2) ampulla, 1.1% (1) esophageal and 7.9%(5) NOS digestive (metastatic with unknown primary). Of the 89 patients with GEP-NEN, 56.2% (50) were diagnosed as grade I, 11.2% (10) as grade II, 20.2% (18) as grade III and 12.4% (11) were considered as mixed adeno-neuroendocrine carcinomas (MANEC). CONCLUSIONS: This study, one of the rare examples based on the 2010 WHO classification of neuroendocrine tumors in the literature, indicates that in the Lebanese population, all duodenal and appendicular tumors are G1 and the majority of MANEC tumors are gastric and pancreatic tumors. Moreover, more duodenal tumors and fewer rectal tumors were encountered in our study compared to European reports. PMID- 27268651 TI - Combination of Potassium Pentagamavunon-0 and Doxorubicin Induces Apoptosis and Cell Cycle Arrest and Inhibits Metastasis in Breast Cancer Cells. AB - A salt compound of a curcumin analogue, potassium pentagamavunon-0 (K PGV-0) has been synthesized to improve solubility of pentagamavunon-0 which has been proven to have anti-proliferative effects on several cancer cells. The purpose of this study was to investigate cytotoxic activity and metastasis inhibition by K PGV- 0 alone and in combination with achemotherapeutic agent, doxorubicin (dox), in breast cancer cells. Based on MTT assay analysis, K PGV-0 showed cytotoxic activity in T47D and 4T1 cell lines with IC50 values of 94.9 MUM and 49.0+/-0.2 MUM, respectively. In general, K PGV-0+dox demonstrated synergistic effects and decreased cell viability up to 84.7% in T47D cells and 62.6% in 4T1 cells. Cell cycle modulation and apoptosis induction were examined by flow cytometry. K PGV-0 and K PGV-0+dox caused cell accumulation in G2/M phase and apoptosis induction. Regarding cancer metastasis, while K PGV-0 alone did not show any inhibition of 4T1 cell migration, K PGV-0+dox exerted inhibition. K PGV-0 and its combination with dox inhibited the activity of MMP-9 which has a pivotal role in extracellular matrix degradation. These results show that a combination of K PGV 0 and doxorubicin inhibits cancer cell growth through cell cycling, apoptosis induction, and inhibition of cell migration and MMP-9 activity. Therefore, K PGV 0 may have potential for development as a co-chemotherapeutic agent. PMID- 27268652 TI - Knowledge of the General Community in Cordoba, Argentina, on Human Papilloma Virus Infection and its Prevention. AB - BACKGROUND: Most studies of human papilloma virus (HPV) are aimed at the natural history of the infection and its relation to cancer; however, there are few studies to assess knowledge of the general population. Our aim was analyze the degree of knowledge of Argentinians about HPV infection and its prevention. MATERIALS AND METHODS: We conducted a voluntary, anonymous and non-binding survey with 27 multiple-choice items, in twelve private and public establishments, selected to include a broad population in terms of education, age and gender. The survey consisted of three sections: individual characteristics of the volunteer, HPV infection basic knowledge, its prevention and the virus relationship with other cancers. RESULTS: One thousand two hundred ninety seven volunteers aged 18 to 80 participated. The total number of correct answers was 45.1%. The correct answers for relationship HPV and cervical cancer was 62.1%. Almost 55% did not know about types of HPV that the vaccines for protection. Statistical analysis showed that women, single people, workers, the better educated, those who have had a STDs or HPV and receiving information through medical or educational establishments had greater knowledge of the topic. Only 0.2% of participants answered all questions correctly. CONCLUSIONS: Knowledge plays an important role in health care and the deficiency found in our population could influence the success of the measures taken in the fight against cervical cancer. In this regard, we believe it would be appropriate, not only to emphasize early diagnosis and vaccine implementation, but also incorporate new communication strategies, facilitating reception of accurate and precise information by all strata of society. PMID- 27268653 TI - Unique Features of Gastric Cancer in Young Patients: Experience from a General Hospital in Nepal. AB - BACKGROUND: Gastric cancer, the fifth most common malignancy in the world, usually affects older individuals but can occur in younger age groups. In this study we compared the clinicopathological profile of young patients of gastric cancer with that of older patients. MATERIALS AND METHODS: It is a prospective study of gastric cancer patients treated over three year period (January 2012 to December 2014). Data of patients were obtained from the medical record. Clinical and pathological characters of younger patients (age 40 years or less) were compared with older patients (age more than 40 years). RESULTS: There were total of 152 patients treated during the study period. Twenty patients (13.2%) were less than 40 years of age and 132 (86.8%) were older. The male to female ratio in younger patients was 1:1.5 whereas in older patients it was 1:0.6. In the younger age group 14 patients (70%) had poorly differentiated adenocarcinoma in contrast to 45% in the older age group (<0.01). Some 55% of younger and 42% of older patients had stage IV disease at presentation and curative surgery was not possible. Palliative surgery for gastric outlet obstruction or bleeding from the tumor was performed on 25% and 21% respectively. CONCLUSIONS: Gastric cancer in young people aged less than 40 years has unique characters like female predominance, unfavorable tumor biology, and advanced stage at presentation. There should be a high index of suspicion of gastric cancer even in young patients. PMID- 27268654 TI - Serum miRNA Panel in Egyptian Patients with Chronic Hepatitis C Related Hepatocellular Carcinoma. AB - BACKGROUND: Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. MicroRNAs (miRNAs) have great HCC diagnostic potential and circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. AIM: To explore the potential benefit of serum miR-126, miR-129, miR-155, miR-203 and miR-223 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related HCC. MATERIALS AND METHODS: The expression of miRNA was evaluated using real-time quantitative RT-PCR in 78 serum samples (30 treatment-naive chronic HCV, 25 post-HCV compensated cirrhosis and 23 treatment- naive HCC cases). RESULTS: Comparing miRNA fold changes in the HCC group vs the non HCC groups, there was significant fold decrease in miR-126 (P= 0.034), miR 129 (P= 0.006), miR-155 (P= 0.011), miR-203 (<0.001) and miR-223 (P= 0.013). The highest AUC to differentiate HCC patients from non-HCC was 0.76 for miR-203. CONCLUSIONS: Among studied miRNAs, serum miR-203 has the highest potential as a non-invasive biomarker of HCC. PMID- 27268655 TI - Prognostic Value of MAC30 Expression in Human Pure Squamous Cell Carcinomas of the Lung. AB - Recent evidence haas indicated that meningioma-associate protein (MAC30) exhibits different expression patterns in various tumors. However, little is known about the value of MAC30 in human squamous cell carcinoma of lung (SQCLC). The purpose of our study was to investigate the expression of MAC30 and to explore its clinical significance in SQCLC patients. A total of 156 Chinese patients diagnosed with SQCLC were selected for this study. The expression of MAC30 in all tissues was confirmed by immunohistochemical staining. Quantitative real-time PCR was performed to analyze MAC30 mRNA expression in 32 cases of SQCLC patients with corresponding non-tumor lung tissues. We observed enhanced mRNA expression of MAC30 in SQCLC as compared to control samples. Further, elevated MAC30 protein expression was strongly associated with poor tumor differentiation, TNM stage, and lymph node metastasis. In addition, we observed that patients with increased MAC30 expression demonstrated poor overall survival. Multivariate analysis explicated that increased MAC30 expression was a valuable independent predictable factor for poor tumor differentiation and short survival in SQCLC patients. Our present study suggests that MAC30 may serve as a biomarker for poor tumor differentiation and outcomes of patients with SQCLC. PMID- 27268656 TI - The Efficacy of Aspirin in Preventing the Recurrence of Colorectal Adenoma: a Renewed Meta-Analysis of Randomized Trials. AB - BACKGROUND: Through search the possible randomized control trials, we make a renewed meta-analysis in order to assess the impact of aspirin in preventing the recurrence of colorectal adenoma. MATERIALS AND METHODS: The Medicine/PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese biomedical literature service system (SinoMed) databases were searched for the related randomized controlled trials until to the April 2016. Three different authors respectively evaluated the quality of studies and extracted data, and we used the STATA software to analyze, investigate heterogeneity between the data, using the fixed-effects model to calculate and merge data. RESULTS: 7 papers were included the renewed meta- analysis, among these studies, two pairs were identified as representing the same study population, with the only difference being the duration of follow-up. Thus there were only five papers included our meta-analysis, and one Chinese paper were also included the work. Results were categorized by the length of follow-up, different kinds of people, varied dose of oral aspirin. The relative of adenoma in patients taking aspirin vs placebo were 0.73 (95% CI 0.55-0.98, P=0.039) with 1 year follow up; 0.84 (95% CI 0.72-0.98, P=0.484) with greater than 1 year follow up; for the advanced adenoma, the RR 0.68 (95% CI 0.49-0.94, P=0.582),for one year; RR=0.75 (95% CI 0.52-1.07, P=0.552) for greater one year. Furthermore the white population could divided into two subgroups according to the different length of follow-up time. When the length of follow-up time less than 3-year, The RR of two subgroups respective were RR=0.86 (95% CI 0.76-0.98, P=0.332), I2=0%, RR=0.68 (95% CI 0.47-0.98, P=0.552), I2=64.6%, But with the extension of follow-up time greater than 2-year, with the white, oral aspirin without considering dose had no efficacy on preventing the recurrence of any adenoma, the RR was 0.86 (95% CI 0.71-1.05, P=0.302), I2=16.4%. CONCLUSIONS: This meta-analysis indicated that oral aspirin is associated with a remarkable decrease in the recurrence of any adenoma and advanced adenomas in patients follow-up for 1 year without concerning the dose of aspirin, but with the extension of follow-up time for greater than 1 year, oral aspirin can be effective on preventing the recurrence of any adenoma, but for the advanced adenoma, the result indicated that oral aspirin had no efficacy, According to the inclusion of ethnic groups, we also divided relevant papers into two subgroups as the yellow and white group. Then the follow-up time was less than 3 years, oral aspirin without considering the dose, had an significant efficacy on preventing the recurrence of any adenoma. But with the follow-up greater than 2 years, oral aspirin had no effect in the white. PMID- 27268657 TI - Downregulated MicroRNA-133a in Gastric Juice as a Clinicopathological Biomarker for Gastric Cancer Screening. AB - Circulatory miR-133a is a marker shared by several types of cancer. In this study we evaluated the feasibility of using miR-133a levels in gastric juice to screen for gastric cancer. A total of 204 samples of gastric juice and mucosa from gastric cancer, atrophic gastritis, gastric ulcer, superficial gastritis and healthy cases were collected by gastroscopy. The results showed that miR-133a levels in gastric juice and carcinoma tissues of patients with gastric cancer were significantly downregulated and positively correlated. Moreover, miR-133a in gastric juice has high operability, high reliability, high sensitivity, high specificity and relative stability, fit for clinical diagnosis of gastric cancer. PMID- 27268658 TI - Antiproliferative Activity of the Methanolic Extract of Withania Somnifera Leaves from Faifa Mountains, Southwest Saudi Arabia, against Several Human Cancer Cell Lines. AB - Cancer represent one of the most serious health problems and major causes of death around the world. Many anticancer drugs in clinical use today are natural products or derived from natural sources. Withania somnifera (L.) Dunal is a small shrub widely distributed in many parts of the world including Saudi Arabia. The antiproliferative activities of the methanolic extract of W. somnifera leaves collected from Faifa mountains, southwest Saudi Arabia against MCF-7, HCT116 and HepH2 cell lines were investigated. The extract showed a strong antiproliferative activity against all cell lines with IC50 values of 3.35, 2.19 and 1.89 MUg/ml, respectively. Flow cytometry results showed that the extract arrested the cell cycle at S phase, and the increase in the caspase 3 activity suggested that the extract could induce cell apoptosis by a caspase mediated pathway. These results demonstrated that the methanolic extract of W. somnifera leaves collected from Faifa mountains has comparable strong antiproliferative activities to samples collected from different locations. PMID- 27268660 TI - Role of Re-irradiation in Salvage Treatment of Glioblastoma Multiforme. PMID- 27268659 TI - Targeted Bisulfite Sequencing-Based Analysis of MGMT Promoter Methylation in Meningiomas. PMID- 27268661 TI - Mutations in PIK3CA Sensitize Breast Cancer Cells to Physiologic Levels of Aspirin. PMID- 27268662 TI - Accessing the medical devices market in Egypt and Saudi Arabia: a systematic review of policies and regulations. AB - INTRODUCTION: Despite the significant medical devices market size in Egypt and Saudi Arabia, information regarding policies and regulations for medical devices market access is highly deficient. AREAS COVERED: The aim of this paper is to provide a systematic review on market access policies and regulations in both countries, to allow safe and timely access to medical technology. The following databases were searched: PubMed, Science Direct, Scopus, and Al Manhal Arabic database. Additionally, the web portals of regulatory authorities of both countries were searched. There are 34 records included in the qualitative synthesis of this review. Expert commentary: Main findings include; adopted regulatory framework from reference countries, and interim main regulatory documents, In conclusion, the market access schemes are relatively structured. However, some recommendations are put forward to navigate towards a more comprehensive policy framework in both countries. PMID- 27268663 TI - Template Synthesis of Decaphyrin without Meso-Bridges: Cyclo[10]pyrrole. AB - An acenaphthylene-fused cyclo[10]pyrrole 1b was selectively synthesized via an oxidative coupling reaction of the corresponding 2,2'-bipyrrole with the appropriate dianion template, croconate anion. The structure of 1b as the isolated largest cyclo[n]pyrrole was elucidated by X-ray crystallographic analysis. The absorption spectrum exhibited a markedly red-shifted, intensified L band at 1982 nm, which was interpreted by application of Michl's perimeter and Gouterman's 4-orbital models, supported by magnetic circular dichroism (MCD) data and theoretical calculations. PMID- 27268664 TI - Monoterpene glycosides from Paeonia veitchii. AB - The EtOH extract of the roots of Paeonia veitchii afforded two new monoterpene glycosides paeonidanin I (1) and paeonidanin J (2), and a new dimeric monoterpene glycoside paeonidanin K (3). Their structures were elucidated on the basis of spectroscopic means and hydrolysis products. PMID- 27268696 TI - Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties. AB - Several isoxazole-containing series of FXR agonists have been published over the last 15years, subsequent to the prototypical amphiphilic 'hammerhead'-type structure that was originally laid out by GW4064, the first potent synthetic FXR agonist. A set of novel compounds where the hammerhead is connected to the terminal carboxylic acid-bearing aryl or heteroaryl moiety by either a cyclopropyl, a hydroxycyclobutyl or a hydroxyazetidinyl linker was synthesized in order to improve upon the ADME properties of such isoxazoles. The resulting compounds all demonstrated high potencies at the target receptor FXR but with considerable differences in their physicochemical and in vivo profiles. The structure-activity relationships for key chemical features that have a major impact on the in vivo pharmacology of this series are discussed. PMID- 27268697 TI - The chemical synthesis and preliminary biological studies of phosphodiester and phosphorothioate analogues of 2-methoxy-lysophosphatidylethanolamine. AB - The chemical synthesis of phosphorothioate/phosphodiester analogues of 2-methoxy lysophosphatidylethanolamine has been described. For the preparation of phosphorothioate derivatives oxathiaphospholane approach has been employed. The phosphodiester compounds were prepared by OXONE(r) oxidation of corresponding phosphorothioates. Each lysophospholipid analogue was synthesized as a series of four compounds, bearing different fatty acid residues both saturated (14:0, 16:0, 18:0) and unsaturated (18:1). The methylation of glycerol 2-hydroxyl function was applied in order to increase the stability of prepared analogues by preventing 1 >2 acyl migration. The cytotoxicity of newly synthesized 2-methoxy lysophosphatidylethanolamine derivatives was evaluated with resazurin-based method in prostate cancer PC3 cell line. The highest reduction of cell viability was noted for LPE analogues containing myristoyl acyl chain. PMID- 27268698 TI - Synthesis of [(11)C]MK-1064 as a new PET radioligand for imaging of orexin-2 receptor. AB - The reference standard MK-1064 {5"-chloro-N-((5,6-dimethoxypyridin-2-yl)methyl) [2,2':5',3"-terpyridine]-3'-carboxamide} was synthesized from methyl 2-chloro-5 iodonicotinate and 5-(chloropyridin-3-yl)boronic acid in 4 steps with 33% overall chemical yield. The precursor desmethyl-MK-1064 {5"-chloro-N-((5-hydroxy-6 methoxypyridin-2-yl)methyl)-[2,2':5',3"-terpyridine]-3'-carboxamide} for radiolabeling was synthesized from 2-bromopyridin-3-ol and 5"-chloro-[2,2':5',3" terpyridine]-3'-carboxylic acid in 6 steps with 17% overall chemical yield. The target tracer [(11)C]MK-1064 {5"-chloro-N-((5-[(11)C]methoxy-6-methoxypyridin-2 yl)methyl)-[2,2':5',3"-terpyridine]-3'-carboxamide} was prepared by O [(11)C]methylation of its corresponding precursor desmethyl-MK-1064 with [(11)C]CH3OTf under basic condition and isolated by a simplified solid-phase extraction (SPE) method in 50-60% decay corrected radiochemical yields based on [(11)C]CO2 at end of bombardment (EOB). The overall synthesis time from EOB was 23min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-555GBq/MUmol. PMID- 27268700 TI - San Fermin all-seeing. PMID- 27268699 TI - Fabrication of Sealed Nanostraw Microdevices for Oral Drug Delivery. AB - The oral route is preferred for systemic drug administration and provides direct access to diseased tissue of the gastrointestinal (GI) tract. However, many drugs have poor absorption upon oral administration due to damaging enzymatic and pH conditions, mucus and cellular permeation barriers, and limited time for drug dissolution. To overcome these limitations and enhance oral drug absorption, micron-scale devices with planar, asymmetric geometries, termed microdevices, have been designed to adhere to the lining of the GI tract and release drug at high concentrations directly toward GI epithelium. Here we seal microdevices with nanostraw membranes-porous nanostructured biomolecule delivery substrates-to enhance the properties of these devices. We demonstrate that the nanostraws facilitate facile drug loading and tunable drug release, limit the influx of external molecules into the sealed drug reservoir, and increase the adhesion of devices to epithelial tissue. These findings highlight the potential of nanostraw microdevices to enhance the oral absorption of a wide range of therapeutics by binding to the lining of the GI tract, providing prolonged and proximal drug release, and reducing the exposure of their payload to drug-degrading biomolecules. PMID- 27268701 TI - Primary lymphocytic lymphoma of lacrimal gland. AB - CASE REPORT: We report a case of primary small-cell lymphocytic lacrimal gland lymphoma in a male diagnosed with primary antiphospholipid syndrome. These rare lymphomas are usually presented in the clinic as disseminations secondary to chronic lymphocytic leukaemia, and the primary site is rare in the orbit. DISCUSSION: Non-Hodgkin lymphomas are a heterogeneous group of tumours. Although treatment in the IE stage is usually radiotherapy, due to its association with antiphospholipid syndrome, systemic treatment with rituximab was administered. PMID- 27268707 TI - In vitro and in vivo studies on the antimicrobial effect of lactoferrin against Escherichia coli O157:H7. AB - Escherichia coli O157:H7 shed by clinically healthy ruminants has been linked to hemorrhagic colitis and the hemolytic uremic syndrome in humans. The bacteria are spread mainly by contaminated food and water, contact with animals carrying the organisms, and person-to-person contact. Although many intervention strategies have been studied to reduce E. coli O157:H7 carriage in ruminants and its spread into the environment, none of the available methods can completely eliminate the infection. Therefore, there is need for new intervention strategies which will effectively reduce E. coli O157:H7 prevalence. Lactoferrin, a member of the transferrin protein family, is an iron-binding glycoprotein that is found in many exocrine secretions, including milk, tears, saliva, and serum. Lactoferrin has a number of biological functions including antimicrobial and immunomodulatory effects. This review summarizes latest data on the antimicrobial effect of lactoferrin against E. coli O157:H7 in in vitro and in vivo studies. PMID- 27268708 TI - Visible-Light-Enabled Decarboxylative Sulfonylation of Cinnamic Acids with Sulfonylhydrazides under Transition-Metal-Free Conditions. AB - Decarboxylative cross-coupling reactions of cinnamic acids with sulfonylhydrazides were explored using oxygen as the sole terminal oxidant, realizing a conceptually novel technology for vinyl sulfone synthesis under the synergistic interactions of visible light irradiation, organic dye-type photocatalyst eosin Y, KI, and Cs2CO3 at room temperature. PMID- 27268709 TI - Cultured Construction: Global Evidence of the Impact of National Values on Piped to-Premises Water Infrastructure Development. AB - In 2016, the global community undertook the Sustainable Development Goals. One of these goals seeks to achieve universal and equitable access to safe and affordable drinking water for all people by the year 2030. In support of this undertaking, this paper seeks to discover the cultural work done by piped water infrastructure across 33 nations with developed and developing economies that have experienced change in the percentage of population served by piped-to premises water infrastructure at the national level of analysis. To do so, I regressed the 1990-2012 change in piped-to-premises water infrastructure coverage against Hofstede's cultural dimensions, controlling for per capita GDP, the 1990 baseline level of coverage, percent urban population, overall 1990-2012 change in improved sanitation (all technologies), and per capita freshwater resources. Separate analyses were carried out for the urban, rural, and aggregate national contexts. Hofstede's dimensions provide a measure of cross-cultural difference; high or low scores are not in any way intended to represent better or worse but rather serve as a quantitative way to compare aggregate preferences for ways of being and doing. High scores in the cultural dimensions of Power Distance, Individualism-Collectivism, and Uncertainty Avoidance explain increased access to piped-to-premises water infrastructure in the rural context. Higher Power Distance and Uncertainty Avoidance scores are also statistically significant for increased coverage in the urban and national aggregate contexts. These results indicate that, as presently conceived, piped-to-premises water infrastructure fits best with spatial contexts that prefer hierarchy and centralized control. Furthermore, water infrastructure is understood to reduce uncertainty regarding the provision of individually valued benefits. The results of this analysis identify global trends that enable engineers and policy makers to design and manage more culturally appropriate and socially sustainable water infrastructure by better fitting technologies to user preferences. PMID- 27268710 TI - Reduction of Water/Oil Interfacial Tension by Model Asphaltenes: The Governing Role of Surface Concentration. AB - In this work, pendant drop techniques and molecular dynamics (MD) simulations were employed to investigate the effect of asphaltene concentrations on the interfacial tension (IFT) of the oil/water interface. Here, oil and asphaltene were represented by, respectively, common organic solvents and Violanthrone-79, and two types of concentration, i.e., bulk concentration and surface concentration, were examined. Correlations between the IFTs from experiments and MD simulations revealed that surface concentration, rather than the commonly used bulk concentration, determines the reduction of oil/water IFTs. Through analyzing the hydrogen bonding, the underlying mechanism for the IFT reduction was proposed. Our discussions here not only enable the direct comparison between experiments and MD simulations on the IFTs but also help with future interfacial studies using combined experimental and simulation approaches. The methodologies used in this work can be extended to many other oil/water interfaces in the presence of interfacially active compounds. PMID- 27268711 TI - Decreasing prevalence of intestinal parasitic infections among school-aged children in Nepal: a systematic review and meta-analysis. AB - BACKGROUND: In the last two decades there have been several studies describing the prevalence of intestinal parasites in Nepal; however, there is a lack of surveillance data in the country. METHODS: We searched literature in PubMed, MEDLINE, EMBASE, Google Scholar and local peer-reviewed journals published from 1990 to 2015 for studies describing prevalence of intestinal parasites among school-aged children. We conducted meta-regression to understand the trend over time and pooled the prevalence using 'metaprop' command in STATA 12.1. RESULTS: Thirty-one studies examining 12 080 fecal specimens were included. The prevalence of intestinal parasitic infections showed a significantly decreasing trend (OR 0.56; 95% CI 0.43-0.73 for each consecutive 5 years) and was similar in males and females. The pooled prevalence in years 1996-2000, 2001-2005, 2006-2010 and 2011 2015 was 61.1% (95% CI 51.47-70.26), 53.2% (95% CI 20.94-83.99), 32.7% (95% CI 26.57-39.21) and 20.4% (95% CI 15.04-26.25), respectively. The proportion of helminths among total intestinal parasites was higher in rural areas 57.6% (95% CI 43.54-71.61), and proportion of protozoa among total intestinal parasites was higher in urban areas 68.4% (95% CI 63.23-73.62). Poly-parasitism was observed in 7.7% (95% CI 5.57-9.73) of children. CONCLUSION: We observed a significantly decreasing trend in prevalence of intestinal parasitic infections among school aged children in Nepal over the last two decades. PMID- 27268712 TI - Yaws: towards the WHO eradication target. AB - In 2012 WHO declared a target to eradicate yaws by 2020. The cornerstone of this strategy is community mass treatment with azithromycin. Initial studies suggest this is a very effective tool that may be capable of interrupting transmission. Alongside this there has been progress in the development and validation of diagnostic tests for yaws. Several new challenges have also emerged, in particular, evidence that Haemophilus ducreyi can cause phenotypically similar ulcers in yaws endemic communities, and evidence for a possible non-human primate reservoir. The 2020 eradication target remains ambitious and more challenges should be expected on the journey. PMID- 27268713 TI - Decrease of microscopic Plasmodium falciparum infection prevalence during pregnancy following IPTp-SP implementation in urban cities of Gabon. AB - BACKGROUND: Six years after the implementation of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) in Gabon, its impact on placental malaria and pregnancy outcomes remains unknown. METHODS: Age, gestational data, use of IPTp-SP and birth weight were recorded during a hospital based cross-sectional survey performed in 2011 in 387 women at the end of pregnancy. RESULTS: Malaria prevalence was 6.7 and 5.3% in peripheral and placental blood respectively. Overall, 59.0% women took at least two IPTp-SP doses which was associated with 50% reduction of Plasmodium; (P.) falciparum infection in primigravidae. Previous malaria treatment was a risk factor for peripheral P. falciparum infection, while uptake of IPTp-SP was associated with reduced parasitaemia. Anaemia prevalence was 38.0%, low birth weight and prematurity rates were 6.0 and 12.0% respectively. Young age was associated with a higher frequency of malaria, anaemia, low birth weight and preterm delivery (p<0.01). Birth weight significantly rose with increasing age (p<0.01), parity (p=0.03) and number of SP doses (p=0.03). A birth weight reduction of 230 g in case of peripheral parasitaemia (p=0.02) and of 210 g with placental parasitaemia (p=0.13) was observed. CONCLUSIONS: Microscopic P. falciparum prevalence during pregnancy significantly declined between 2005 and 2011, following IPTp-SP implementation in Gabon. Young women and paucigravidae remain the most susceptible to malaria and associated outcomes. PMID- 27268714 TI - The Leishmaniasis East Africa Platform (LEAP): strengthening clinical trial capacity in resource-limited countries to deliver new treatments for visceral leishmaniasis. AB - Visceral leishmaniasis is a neglected tropical disease endemic in East Africa where improved patient-adapted treatments are needed. The Leishmaniasis East Africa Platform (LEAP) was created in 2003 to strengthen clinical research capacity, serve as a base for training, and evaluate and facilitate implementation of new treatments. Major infrastructure upgrades and personnel training have been carried out. A short course of Sodium Stibogluconate and Paramomycin (SSG&PM) was evaluated and is now first-line treatment in the region; alternative treatments have also been assessed. LEAP can serve as a successful model of collaboration between different partners and countries when conducting clinical research in endemic countries to international standards. PMID- 27268715 TI - Testing the monophyly of Aesculus L. and Billia Peyr., woody genera of tribe Hippocastaneae of the Sapindaceae. AB - Hippocastaneae is a well-supported clade in Sapindaceae that comprises 15+ species; 12+ in Aesculus, two in Billia, and one in Handeliodendron Rehder. The monophyly of Aesculus and Billia were widely assumed, but a recent molecular phylogenetic study of Sapindanceae used seven species of Aesculus and one each of Billia and Handeliodendron and showed that Billia and Handeliodendron were nested within Aesculus. Here, we tested the hypothesis that Aesculus and Billia are mutually monophyletic using phylogenetic analyses of seven molecular markers and 31 accessions of Hippocastaneae representing 14 species. We performed phylogenetic analyses using a dataset of concatenated genes as well as with coalescent method for constructing a species tree from individual gene trees. The analysis of seven concatenated markers and the species tree strongly supported the mutual monophyly of Aesculus and Billia. We also recovered support for the traditional arrangement of genera within Hippocastaneae: Aesculus and Billia comprising a clade that is sister to Handeliodendron. However, the relationships among the genera remain incompletely resolved. PMID- 27268716 TI - Audiovestibular function in patients with juvenile idiopathic arthritis (JIA). AB - CONCLUSION: It was found that JIR children had potential sensory neural hearing loss and vestibular affection. Therefore, this study recommends: early complete audiologic evaluation of JIA child followed by regular follow-up, including TOAEs, extended high-frequency audiometry, and VNG. This follow-up is important for preliminary diagnosis and management in order to prevent the negative impact of hearing loss on a child's life. OBJECTIVE: The aim of this study was to assess hearing in children with Juvenile idiopathic arthritis (JIA) and compare them with a healthy control group. In addition to conventional audiometry, extended high-frequency audiometry and Transient otoacoustic emission (TOAEs) were used. This study also tried to investigate the vestibular function in JIR children by videonystagmography (VNG). PATIENTS AND METHODS: The study group comprised of 28 children with JIR and 28 healthy children. All subjects were examined audiologically using basic audiological evaluation, high-frequency audiometry, TOAEs, and VNG. RESULTS: Children with JIR had apparent normal peripheral hearing in conventional audiometry; sub-clinical sensory neural hearing loss was detected. This sub-clinical hearing loss appeared in statistically significant difference between them and normal in high-frequency audiometry and TOAEs. VNG test results showed affected tracking and second tests. PMID- 27268717 TI - Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing. AB - Previous studies showed that cannabinoid 2 (CB2) receptor is expressed in multiple effector cells during skin wound healing. Meanwhile, its functional involvement in inflammation, fibrosis, and cell proliferation in other organs and skin diseases implied CB2 receptor might also regulate skin wound healing. To verify this hypothesis, mice excisional wounds were created and treated with highly selective CB2 receptor agonist GP1a (1-(2,4-dichlorophenyl)-6-methyl- N piperidin-1-yl-4H-indeno[1,2-c]pyrazole-3-carboxamide) and antagonist AM630 ([6 iodo-2- methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-(4-methoxyphenyl)methanone) respectively. The inflammatory infiltration, cytokine expression, fibrogenesis, and wound re-epithelialization were analyzed. After CB2 receptor activation, neutrophil and macrophage infiltrations were reduced, and expressions of monocyte chemotactic protein (MCP)-1, stromal cell-derived factor (SDF)-1, Interleukin (IL)-6, IL-1beta, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1 and vascular endothelial growth factor (VEGF)-A were decreased. Keratinocyte proliferation and migration were enhanced. Wound re epithelialization was accelerated. Fibroblast accumulation and fibroblast-to myofibroblast transformation were attenuated, and expression of pro-collagen I was decreased. Furthermore, HaCaT cells in vitro were treated with GP1a or AM630, which revealed that CB2 receptor activation promoted keratinocyte migration by inducing the epithelial to mesenchymal transition. These results, taken together, indicate that activating CB2 receptor could ameliorate wound healing by reducing inflammation, accelerating re-epithelialization, and attenuating scar formation. Thus, CB2 receptor agonist might be a novel perspective for skin wound therapy. PMID- 27268718 TI - Taurochenodeoxycholic acid induces NR8383 cells apoptosis via PKC/JNK-dependent pathway. AB - Our former studies have suggested that taurochenodeoxycholic acid (TCDCA) as a signaling molecule shows obvious anti-inflammatory and immune regulation properties. In this research, we tentatively explored the potential effects and the possible mechanism that involve in the apoptotic process in NR8383 cells induced by TCDCA. Using flow cytometry analysis, we evaluated the apoptosis rate. Gene expression levels were determined by qPCR. The expressions of protein kinase C (PKC), Jun N-terminal kinase (JNK) and their phosphorylation were measured by Western Blot. We observed the activities of caspase-3 and caspase-8 with Caspase Glo(r) regent. The results demonstrated that TCDCA dramatically improved the apoptosis rate of NR8383 cells in a concentration-dependent manner. In the meantime, PKC mRNA levels and activities were significantly augmented by TCDCA treatments. In addition, JNK, caspase-3 and caspase-8 mRNA expression levels and activities were increased by TCDCA, while they were markedly decreased by specific inhibitors. We conclude that TCDCA contributes to the apoptosis through the activation of the caspase cascade in NR8383 cells, and the PKC/JNK signaling pathway may be involved in this process. These results indicate that TCDCA may be a latent effective pharmaceutical product for apoptosis-related diseases. PMID- 27268719 TI - Morin, a dietary bioflavonol suppresses monosodium urate crystal-induced inflammation in an animal model of acute gouty arthritis with reference to NLRP3 inflammasome, hypo-xanthine phospho-ribosyl transferase, and inflammatory mediators. AB - The anti-inflammatory effect of morin, a dietary bioflavanol was explored on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Morin treatment (30mg/kg b.wt) significantly attenuated the ankle swelling and the levels of lipid peroxidation, nitric oxide, serum pro-inflammatory cytokines (tumor necrosis factor (TNF) -alpha, interleukin (IL)-1beta, and IL-6), monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and articular elastase along with an increased anti-oxidant status (catalase (CAT) and superoxide dismutase (SOD)) in the joint homogenate of MSU crystal-induced rats. Histological assessment revealed that morin limited the diffusion of joint space, synovial hyperplasia, and inflammatory cell infiltrations. The mRNA expression of NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasome, caspase-1, pro-inflammatory cytokines, MCP-1, inflammatory enzymes (inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2)), and nuclear factor-kappa B (NF-kappaB) p65 was found downregulated and HPRT (hypo-xanthine phospho-ribosyl transferase) mRNA expression was upregulated in morin treated MSU crystal-induced rats. In addition, morin treatment reduced the protein expression of NF-kappaB p65, p-NF-kappaB p65, iNOS, COX-2, and TNF-alpha. The results clearly demonstrated that morin exert a potent anti-inflammatory effect on MSU crystal-induced inflammation in rats. PMID- 27268720 TI - Mobile Electronic Medical Records Promote Workflow: Physicians' Perspective From a Survey. AB - BACKGROUND: As a result of demographic changes, physicians are required to deliver needed services with limited resources. Research suggests that tablet PCs with access to patient data may streamline clinical workflow. A recent study found tablets with mobile electronic medical records (EMRs) can facilitate data retrieval and produce time savings across the clinical routine within hospital settings. However, the reasons for these time savings, including details on how tablets were being used, remain unclear. The same applies to physicians' perceptions of this tool within an inpatient setting. OBJECTIVE: This study examined physicians' perception of tablets with EMRs in an inpatient setting. The rationale was to identify both subjective and objective factors that impacted the successful implementation and use of tablets running an EMR. METHODS: We developed a 57-item survey questionnaire designed to examine users' perception of and attitude toward tablets, which was administered to 14 participating physicians following 7 weeks of tablet use. Five participants volunteered to participate in a second study that investigated physicians' patterns of tablet use within the EMR environment by digitally tracking and storing usage behavior. Statistical analyses of questionnaire results included mean values with their bootstrapped 95% confidence intervals and multivariate analysis of variance to identify predictors of tablet use. RESULTS: Physicians reported high degrees of satisfaction with the tablets. There was a general consensus among physicians that tablet use streamlined clinical workflow through optimized data retrieval (rated 0.69, 0.23-1.15 points better than control) and improved communication with patients and other physicians (rated 0.85, 0.54-1.15 and 0.77, 0.38-1.15 points better than control, respectively). Age (F3,11=3.54, P=.04), occupational group (F1,11=7.17, P=.04), and attitude toward novel technologies (F1,11=10.54, P=.02) predicted physicians' satisfaction with the devices and their motivation regarding their further use. Tracking data yielded that only a few of the available functions were used frequently. CONCLUSIONS: Although tablet PCs were consistently perceived as beneficial, several factors contributed to the fact that their full potential was not fully exploited. Training in functionality and providing a reliable infrastructure might foster successful tablet implementation. PMID- 27268721 TI - Photocatalytic Properties of TiO2 Composites Immobilized with Gold Nanoparticle Assemblies Using the Streptavidin-Biotin Interaction. AB - A method using biomolecules to precisely fabricate the morphology of metal nanoparticles immobilized on the surface of a semiconductor using biomolecules is described. A biotin moiety (Biot) is introduced onto the surface of a gold nanoparticle (AuNP) by covalent coupling with alpha-lipoic acid to assemble AuNPs in the presence of streptavidin (STV). The assembly of Biot-AuNP/STV is immobilized on the surface of TiO2 chemically modified with 1-(3 aminopropyl)silatrane (APS) to provide a positively charged surface. The Au content immobilized on the surface of TiO2 is clearly increased to 9.5 wt % (Au) as a result of the STV-biotin interaction and the electrostatic interaction between negatively charged Biot-AuNPs and the positively charged surface of APS/TiO2. Transmission electron microscopy (TEM) analysis reveals that the composite has an ordered surface geometry in which Biot-AuNPs are spread over the composite surface in two dimensions. The photocatalytic activity toward decomposition of methyl orange dye promoted by this composite is 55%, which is higher than that of the other composites. The Biot-AuNP/STV@APS/TiO2 composite efficiently reduces O2 molecules at Eonset = -0.23 V vs Ag|AgCl, which is more positive than that of other composites (Eonset = -0.40 to -0.32 V). The result suggests that an increased number of AuNPs immobilized in close contact with the TiO2 surface facilitates photoinduced charge transfer. This strategy, which takes advantage of the specific interactions provided by biomolecules and the chemical modification on the surface, has remarkable potential for efficient fabrication of metal nanoparticles on the surface of the semiconductor, which accelerates the reduction of oxygen molecules. PMID- 27268722 TI - Stimulation of biofilm formation by oxidative stress in Campylobacter jejuni under aerobic conditions. PMID- 27268723 TI - Analysis of Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome Defined on the Basis of Bronchodilator Response and Degree of Emphysema. AB - RATIONALE: Despite the increasing recognition of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) as a clinical entity, it remains poorly characterized due to a lack of agreement on its definition and diagnostic criteria. OBJECTIVES: The aim of this study was to use spirometry and computed tomography (CT) to help better define ACOS as well as to classify subjects with ACOS based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) letter grade. METHODS: We analyzed 10,192 subjects enrolled in the COPDGene Study. Subjects were non-Hispanic white or African American current or former smokers aged 45-80 years with at least a 10-pack-year smoking history. Subjects were categorized as having either ACOS with a bronchodilator response or chronic obstructive pulmonary disease with emphysema on the basis of spirometry, high resolution CT, and a history of asthma or hay fever. MEASUREMENTS AND MAIN RESULTS: Subjects with ACOS were younger (60.6 vs. 65.9 years old; P < 0.0001), more likely to be African American (26.8% vs. 14.4%; P < 0.0001), had a higher body mass index (29.6 vs. 25.1 kg/m(2); P < 0.0001), and were more likely to be current smokers (50.9% vs. 20.7%; P < 0.0001). The majority of subjects with ACOS were categorized as GOLD grade B. Despite less severe spirometry and CT findings in subjects with ACOS, there was no significant difference in severe or frequent exacerbations. CONCLUSIONS: Bronchodilator responsiveness and degree of emphysema can help define ACOS. When defined on the basis of bronchodilator responsiveness and degree of emphysema, patients with ACOS represent a unique and high-risk group with distinct clinical features. PMID- 27268725 TI - Predictors of sexual behaviour among men and women in New York City area prisons. AB - The USA currently has the highest incarceration rate in the world. Individuals at greatest risk for HIV also tend to be among those at an elevated risk for incarceration. The HIV epidemic is driven by injection drug use and sexual behaviour, and estimates of prison-based sexual behaviour vary widely. This study examined sexual behaviour among 1369 incarcerated men and women in the New York City area. Approximately 13% of the sample (n = 176) reported being sexually active while incarcerated over the previous 6 months. Multiple logistic regression models were used to examine the predictors of prison sexual behaviour. The following variables were associated with increased odds of sexual activity in the previous six months: female gender (OR = 3.28; 95%CI = 1.95,5.51), Black race (OR = 2.26; 95%CI = 1.47,3.46), history of drug use (OR = 1.85; 95%CI = 1.04,3.30), bisexual (OR = 3.19; 95%CI = 1.90,5.38) or homosexual identity (OR = 8.50; 95%CI = 3.92,18.43) and conjugal visitation programme participation (OR = 66.26; 95%CI = 31.42,139.74). Educational programmes regarding sexually transmitted infections and appropriate harm reduction measures are warranted for this population. The expansion of conjugal visitation programmes may also be useful in helping prisoners sustain their relationships with partners from their community and reduce the risk of infectious disease transmission in this environment. PMID- 27268724 TI - Surface-Enhanced Raman Spectroscopy Biosensing: In Vivo Diagnostics and Multimodal Imaging. AB - This perspective presents recent developments in the application of surface enhanced Raman spectroscopy (SERS) to biosensing, with a focus on in vivo diagnostics. We describe the concepts and methodologies developed to date and the target analytes that can be detected. We also discuss how SERS has evolved from a "point-and-shoot" stand-alone technique in an analytical chemistry laboratory to an integrated quantitative analytical tool for multimodal imaging diagnostics. Finally, we offer a guide to the future of SERS in the context of clinical diagnostics. PMID- 27268726 TI - Oncology outcomes in Retroperitoneal sarcomas: Prognostic factors in a Retrospective Cohort study. AB - INTRODUCTION: Retroperitoneal sarcomas are a rare group of malignant soft tissue tumors with a generally poor prognosis. The aim of the study was to define the demographic characteristics and prognostic factors for patients with retroperitoneal sarcomas (RPS) in a Tertiary Referral Center at Mexico. METHODS: A retrospective study of patients with RPS treated from January 2005 to December 2012 at the National Cancer Institute at Mexico. Patient, tumor and treatment variables were analyzed including use of adjuvant therapy and survival status. Survival and local recurrence curves were estimated using the Kaplan-Meier method. RESULTS: Ninety-five patients with a mean age of 47 years with retroperitoneal sarcoma were included. Median follow-up was 25 months (range 1 108 months). The average tumor size was 23.7 cm. Histology, 58 (61.1%) were liposarcoma, 14 (14.7%), leiomyosarcomas and 23 (24.2%) were from other histologies. In 64 (67.4%) patients were high-grade malignancies. The median survival was 51 months for patients with complete resection, 25.1 months for those with incomplete resection, and 4.4 months for those with unresectable tumors. Complete resection (p = 0.0001), and liposarcoma (p = 0.03) were prognostic factors for overall survival. CONCLUSION: In this study of patients with retroperitoneal, complete resection and liposarcoma histology are prognostic factors related to the disease-free and overall survival. Patients approached with curative intent should undergo aggressive attempts at complete surgical resection. PMID- 27268727 TI - Identification and characterization of a chitin deacetylase from a metagenomic library of deep-sea sediments of the Arctic Ocean. AB - BACKGROUND: The chemical and biological compositions of deep-sea sediments are interesting because of the underexplored diversity when it comes to bioprospecting. The special geographical location and climates make Arctic Ocean a unique ocean area containing an abundance of microbial resources. METHODS: A metagenomic library was constructed based on the deep-sea sediments of Arctic Ocean. Part of insertion fragments of this library were sequenced. A chitin deacetylase gene, cdaYJ, was identified and characterized. RESULTS: A metagenomic library with 2750 clones was obtained and ten clones were sequenced. Results revealed several interesting genes, including a chitin deacetylase coding sequence, cdaYJ. The CdaYJ is homologous to some known chitin deacetylases and contains conserved chitin deacetylase active sites. CdaYJ protein exhibits a long N-terminal and a relative short C-terminal. Phylogenetic analysis revealed that CdaYJ showed highest homology to CDAs from Alphaproteobacteria. The cdaYJ gene was subcloned into the pET-28a vector and the recombinant CdaYJ (rCdaYJ) was expressed in Escherichia coli BL21 (DE3). rCdaYJ showed a molecular weight of 43kDa, and exhibited deacetylation activity by using p-nitroacetanilide as substrate. The optimal pH and temperature of rCdaYJ were tested as pH7.4 and 28 degrees C, respectively. CONCLUSIONS: The construction of metagenomic library of the Arctic deep-sea sediments provides us an opportunity to look into the microbial communities and exploiting valuable gene resources. A chitin deacetylase CdaYJ was identified from the library. It showed highest deacetylation activity under slight alkaline and low temperature conditions. CdaYJ might be a candidate chitin deacetylase that possesses industrial and pharmaceutical potentials. PMID- 27268728 TI - LncRNA-uc.167 influences cell proliferation, apoptosis and differentiation of P19 cells by regulating Mef2c. AB - In our previous study we screened thousands of lncRNAs for their relationship with ventricular septal defect. Among these lncRNAs, uc.167 attracted our attention for its high level of conservation and that it was antisense to the Mef2c gene, which encodes myocyte enhancer factor 2C. This study aims to investigate the role of uc.167 during cardiomyocyte maturation in P19 cells induction and possible mechanism. The uc.167 expression level in human heart tissue of ventricular septum defect (VSD) was evaluated by qRT-PCR. The UCSC database was searched to investigate the bioinformatics of uc.167. We constructed overexpression vector of uc.167 and Mef2c. To detect proliferation and apoptosis, we combined cell cycle analysis and CCK8, Hoechst staining, flow cytometry and caspase-3 assays, respectively. The cardiomyogenesis related RNAs (cTnT, GATA4, and Mef2c) and proteins were detected by qRT-PCR and Western blotting. In this study, we found that uc.167 expression was significantly increased in VSD heart tissues. uc.167 is on the opposite strand to the coding gene Mef2c. The expression model of Mef2c and uc.167 showed an opposite correlation in the embryonic development and process of differentiation of P19 cells into cardiomyocytes. Overexpression of uc.167 inhibited proliferation but promoted apoptosis in P19 cells compared with the vector group, and those relative mRNAs and proteins decreased during the differentiation process. Whereas, co-expression of Mef2c and uc.167 can partially reverse the negative effects of uc.167 on proliferation, apoptosis and differentiation. Taken together, our findings suggest that uc.167 contributes to the development potential of VSD and may constitute a potential therapeutic target in this disease. uc.167 influences cell proliferation, apoptosis and differentiation of P19 cell by regulating Mef2c. PMID- 27268729 TI - SPARC (secreted protein acidic and rich in cysteine) of the intestinal nematode Strongyloides ratti is involved in mucosa-associated parasite-host interaction. AB - The secreted protein acidic and rich in cysteine (SPARC), found in the excretory/secretory products of Strongyloides ratti, is most strongly expressed in parasitic females. Since SPARC proteins are involved in the modulation of cell matrix interactions, a role of the secreted S. ratti SPARC (Sr-SPARC) in the manifestation of the parasite in the host's intestine is postulated. The full length cDNA of Sr-SPARC was identified and the protein was recombinantly expressed. The purified protein was biologically active, able to bind calcium, and to attach to mucosa-associated human cells. Addition of Sr-SPARC to an in vitro mucosal three-dimensional-cell culture model led to a time-dependent release of the cytokines TNF-alpha, IL-22, IL-10 and TSLP. Of importance, exposure with Sr-SPARC fostered wound closure in an intestinal epithelial cell model. Here, we demonstrate for the first time that SPARC released from the nematode is a multifunctional protein affecting the mucosal immune system. PMID- 27268730 TI - Heterogeneity of the serine synthetic pathway in Entamoeba species. AB - Phosphoserine phosphatase (PSP) catalyzes the third step of the phosphorylated serine biosynthetic pathway, and occurred multiple times in evolution, while enzymes catalyzing the first and second steps in the pathway have single respective origins. In the present study, we examined the existence of PSP among genus Entamoeba including a human enteric parasite, Entamoeba histolytica. E. histolytica as well as majority of Entamoeba species have the first and second enzymes, but lacks PSP. In contrast, a reptilian enteric parasite, Entamoeba invadens possesses canonical PSP. Thus, there are variations in the existence of the serine biosynthetic ability among Entamoeba species. PMID- 27268731 TI - Enhanced Hydrothermal Stability and Catalytic Performance of HKUST-1 by Incorporating Carboxyl-Functionalized Attapulgite. AB - Much attention has been paid to metal-organic frameworks (MOFs) due to their large surface areas, tunable functionality, and diverse structure. Nevertheless, most reported MOFs show poor hydrothermal stability, which seriously hinders their applications. Here a strategy is adopted to tailor the properties of MOFs by means of incorporating carboxyl-functionalized natural clay attapulgite (ATP) into HKUST-1, a well-known MOF. A new type of hybrid material was thus fabricated from the hybridization of HKUST-1 and ATP. Our results indicated that the hydrothermal stability of the MOFs as well as the catalytic performance was apparently improved. The frameworks of HKUST-1 were severely destroyed after hydrothermal treatment (hot water vapor, 60 degrees C), while that of the hybrid materials was maintained. For the hybrid materials containing 8.4 wt % of ATP, the surface area reached 1302 m(2).g(-1) and was even higher than that of pristine HKUST-1 (1245 m(2).g(-1)). In the ring-opening of styrene oxide, the conversion reached 98.9% at only 20 min under catalysis from the hybrid material, which was obviously higher than that over pristine HKUST-1 (80.9%). Moreover, the hybrid materials showed excellent reusability and the catalytic activity was recoverable without loss after six cycles. Our materials provide promising candidates for heterogeneous catalysis owing to the good catalytic activity and reusability. PMID- 27268732 TI - Investigating the real-world emission characteristics of light-duty gasoline vehicles and their relationship to local socioeconomic conditions in three communities in Los Angeles, California. AB - This paper discusses results from a vehicular emissions research study of over 350 vehicles conducted in three communities in Los Angeles, CA, in 2010 using vehicle chase measurements. The study explores the real-world emission behavior of light-duty gasoline vehicles, characterizes real-world super-emitters in the different regions, and investigates the relationship of on-road vehicle emissions with the socioeconomic status (SES) of the region. The study found that in comparison to a 2007 earlier study in a neighboring community, vehicle emissions for all measured pollutants had experienced a significant reduction over the years, with oxides of nitrogen (NOX) and black carbon (BC) emissions showing the largest reductions. Mean emission factors of the sampled vehicles in low-SES communities were roughly 2-3 times higher for NOX, BC, carbon monoxide, and ultrafine particles, and 4-11 times greater for fine particulate matter (PM2.5) than for vehicles in the high-SES neighborhood. Further analysis indicated that the emission factors of vehicles within a technology group were also higher in low-SES communities compared to similar vehicles in the high-SES community, suggesting that vehicle age alone did not explain the higher vehicular emission in low-SES communities. Evaluation of the emission factor distribution found that emissions from 12% of the sampled vehicles were greater than five times the mean from all of the sampled fleet, and these vehicles were consequently categorized as "real-world super-emitters." Low-SES communities had approximately twice as many super-emitters for most of the pollutants as compared to the high-SES community. Vehicle emissions calculated using model-year-specific average fuel consumption assumptions suggested that approximately 5% of the sampled vehicles accounted for nearly half of the total CO, PM2.5, and UFP emissions, and 15% of the vehicles were responsible for more than half of the total NOX and BC emissions from the vehicles sampled during the study. IMPLICATIONS: This study evaluated the real-world emission behavior and super-emitter distribution of light-duty gasoline vehicles in California, and investigated the relationship of on-road vehicle emissions with local socioeconomic conditions. The study observed a significant reduction in vehicle emissions for all measured pollutants when compared to an earlier study in Wilmington, CA, and found a higher prevalence of high-emitting vehicles in low-socioeconomic-status communities. As overall fleet emissions decrease from stringent vehicle emission regulations, a small fraction of the fleet may contribute to a disproportionate share of the overall on-road vehicle emissions. Therefore, this work will have important implications for improving air quality and public health, especially in low-SES communities. PMID- 27268733 TI - A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy. AB - Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model. PMID- 27268735 TI - Data analytics identify glycated haemoglobin co-markers for type 2 diabetes mellitus diagnosis. AB - Glycated haemoglobin (HbA1c) is being more commonly used as an alternative test for the identification of type 2 diabetes mellitus (T2DM) or to add to fasting blood glucose level and oral glucose tolerance test results, because it is easily obtained using point-of-care technology and represents long-term blood sugar levels. HbA1c cut-off values of 6.5% or above have been recommended for clinical use based on the presence of diabetic comorbidities from population studies. However, outcomes of large trials with a HbA1c of 6.5% as a cut-off have been inconsistent for a diagnosis of T2DM. This suggests that a HbA1c cut-off of 6.5% as a single marker may not be sensitive enough or be too simple and miss individuals at risk or with already overt, undiagnosed diabetes. In this study, data mining algorithms have been applied on a large clinical dataset to identify an optimal cut-off value for HbA1c and to identify whether additional biomarkers can be used together with HbA1c to enhance diagnostic accuracy of T2DM. T2DM classification accuracy increased if 8-hydroxy-2-deoxyguanosine (8-OhdG), an oxidative stress marker, was included in the algorithm from 78.71% for HbA1c at 6.5% to 86.64%. A similar result was obtained when interleukin-6 (IL-6) was included (accuracy=85.63%) but with a lower optimal HbA1c range between 5.73 and 6.22%. The application of data analytics to medical records from the Diabetes Screening programme demonstrates that data analytics, combined with large clinical datasets can be used to identify clinically appropriate cut-off values and identify novel biomarkers that when included improve the accuracy of T2DM diagnosis even when HbA1c levels are below or equal to the current cut-off of 6.5%. PMID- 27268734 TI - Antioxidant-Mediated Modulation of Protein Reactivity for 3,4 Dihydroxyphenylacetaldehyde, a Toxic Dopamine Metabolite. AB - 3,4-Dihydroxyphenylacetaldehyde (DOPAL) is an endogenously produced toxic aldehyde. It is a bifunctional electrophile implicated in the loss of dopaminergic cells concomitant with Parkinson's disease and neurodegeneration. DOPAL is known to react with proteins and amino acids such as N-acetyl lysine (NAL); oxidation of the catechol moiety to the quinone of DOPAL increases this reactivity. Here, we demonstrate the ability of the antioxidants N acetylcysteine, glutathione, and ascorbic acid to mitigate the reactivity of DOPAL with proteins and amino acids in a dose-dependent fashion. Conversely, Trolox did not lessen the observed reactivity with proteins. Interestingly, use of tricine, a buffer and reducing agent, in these systems also decreased the reactivity of DOPAL with amines, yielding tricine-derived free radical species. Modification of amines with aldehydes typically involves Schiff base chemistry; however, the observance of free radicals suggests that an oxidative step is involved in the reaction of DOPAL with lysine. Furthermore, while Schiff base formation is usually optimal at pH 5, the reaction rate of DOPAL with NAL is negligible at pH 5 and is enhanced under basic conditions (e.g., pH 9). Conditions of high pH are also favorable for catechol auto-oxidation, known to occur for DOPAL. The antioxidant-mediated protection demonstrated here suggests that oxidative stress may impart cellular vulnerability to protein modification by DOPAL. Therefore, depleted antioxidants and increased levels of lipid peroxidation products, known to prevent the detoxifying metabolism of DOPAL, may present a survival challenge to dopaminergic cells targeted in Parkinson's disease. PMID- 27268736 TI - Automatic limb identification and sleeping parameters assessment for pressure ulcer prevention. AB - Pressure ulcers (PUs) are common among vulnerable patients such as elderly, bedridden and diabetic. PUs are very painful for patients and costly for hospitals and nursing homes. Assessment of sleeping parameters on at-risk limbs is critical for ulcer prevention. An effective assessment depends on automatic identification and tracking of at-risk limbs. An accurate limb identification can be used to analyze the pressure distribution and assess risk for each limb. In this paper, we propose a graph-based clustering approach to extract the body limbs from the pressure data collected by a commercial pressure map system. A robust signature-based technique is employed to automatically label each limb. Finally, an assessment technique is applied to evaluate the experienced stress by each limb over time. The experimental results indicate high performance and more than 94% average accuracy of the proposed approach. PMID- 27268738 TI - Dhis and Dhat: Evidence of Semen Retention Syndrome Amongst White Britons. AB - The uncritical application of western psychiatric concepts in non-western societies resulting in culturally invalid psychiatric syndromes, have been extensively documented. Such instances are considered 'category errors'. In contrast, 'reverse category errors' although theoretically postulated, have never been empirically demonstrated. Diagnostic criteria of an established South Asian culture specific neurosis, Dhat syndrome, were deployed by a psychiatrist of South Asian origin, amongst 47 white Britons in London, UK, presenting for the first time with a clinic diagnosis of ICD-9 Depressive Neurosis (Dysthymic Disroder, ICD-11). The proceedure yielded a new disorder, Semen Retention Syndrome. Based on narrative accounts and quantitative scores on the Hamilton Depression Rating Scale, the evidence suggests that a significant subset of white British subjects diagnosed with Dysthymic Disorder, may in fact be expressing a psychological variation of a previously unknown local White British somatisation phenomena labelled Semen Retention Syndrome. Anxiety and depressive symptoms presented by this subset of subjects were primarily attributed to a core irrational belief and a cognitive error centered around misunderstood concepts of semen physiology. Consequently, the undue focus on mood idioms by both white British patients and their health professionals, leads to a mistaken diagnosis of Mood Disorder, and results in incorrect treatment. The implications of this ethnocentric mode of reasoning raises concerns about existing concepts in psychiatric phenomenology and for official international diagnostic classificatory systems. The paper concludes by arguing that category errors in both directions are instances of cultural iatrogenesis, and underscore the importance of a culturally valid psychiatry. PMID- 27268737 TI - Implantable and transdermal polymeric drug delivery technologies for the treatment of central nervous system disorders. AB - The complexity of the brain and the membranous blood-brain barrier (BBB) has proved to be a significant limitation to the systemic delivery of pharmaceuticals to the brain rendering them sub-therapeutic and ineffective in the treatment of neurological diseases. Apart from this, lack of innovation in product development to counteract the problem is also a major contributing factor to a poor therapeutic outcome. Various innovative strategies show potential in treating some of the neurological disorders; however, drug delivery remains the most popular. To attain therapeutic drug levels in the central nervous system, large, intolerable systemic doses are generally administered. The major factors responsible for the success maintenance therapy of neurological diseases included controlled and sustained release of neurotherapeutics, reduced frequency of administration, higher bioavailability, and patient compliances. Conventional oral or injectable formulations cannot satisfy all the requirements in many circumstances. This article reviews the therapeutic implantable polymeric and transdermal devices employed in an attempt to effectively achieve therapeutic quantities of drug across the BBB over a prolonged period, to improve patient disease prognosis. PMID- 27268739 TI - Semen Anxiety: Materiality, Agency and the Internet. AB - Semen is a potent cultural symbol of masculinity. The social life of semen is poorly understood because of the intensely personal nature of its being. But the Internet has opened up new avenues for people to explore sensitive issues without disclosing their identity. This paper examines a set of questions submitted anonymously for answering by a medical team over a three month period to a UK based consumer health website. The questions are analysed for emergent themes and these are divided into three groups: those concerning the material quality of semen; semen relating to masturbation; and those that concern semen and potency. It argues that far from being a phenomenon isolated to non-western cultures, semen anxiety is present in the UK in the twenty-first century and is the expression of anxieties surrounding shifting gender roles and masculine identities. PMID- 27268740 TI - Toxic Emissions: The Role of Semen in GWS Narratives. AB - Narratives about Gulf War Syndrome (GWS) contain discussions of sex and reproduction and there is a high level of anxiety about these subjects. Although similar to other medically unexplained conditions, GWS has distinctive features. The most salient of these is its contagious nature, with the main vehicle for contamination being semen. GWS sufferers believe their semen to be affected by their participation in the Gulf War. This paper focuses on a number of specific symptoms described by Gulf veterans including: Burning Semen Syndrome, low libido, impotence and birth defects and aims to interpret why certain symptoms became powerful markers of the condition. Furthermore, the paper looks at the meaning conveyed by such symptom reporting. Data were generated from 14 months ethnographic fieldwork in the UK including participant observation, semi structured interviews and document analysis. Concerns about lack of potency, toxicity and quality suggest that semen itself is a substance in which social concerns are enacted. The paper argues that such a focus on and anxiety about semen suggests that GWS narratives express concerns about masculinity, or, more precisely a loss of masculinity. PMID- 27268741 TI - 'Pass the Cream, Hold the Butter': Meanings of HIV Positive Semen for Bugchasers and Giftgivers. AB - It has been argued by some that sexual health campaigns' ignorance of the richness of meanings associated with semen for gay men has actually led to an increase in the spread of HIV/AIDS(Rofes 1996 ). This paper reviews some of these meanings and their employment among a group of gay men who actively want to be infected with HIV as well as wanting to infect others ('bugchasers' and 'giftgivers'). Based on the analysis of exchanges posted on a website used by bugchasers and giftgivers, this research asks if the attitude towards semen of men who apparently actively seek and spread HIV infection, an extreme act, would be equally extreme. It attempts to show that despite the extreme negativity and apparent sexual transgression engaged in by these men, their conceptions of what semen is and does is quite normative-semen causes pregnancy. These findings illustrate both that semen has the same richness of meaning for gay men as for the heterosexual population. Therefore, semen's meanings cannot be ignored when attempting to educate men about sexual practices. Bugchasing and giftgiving as behaviours and discourse that employ HIV infected semen containing the men's DNA are a way of overcoming the sense of isolation that results from 'cold, sterile', protected sex, despite their initial appearance as abject, transgressive and destructive. PMID- 27268742 TI - Body Praxis and Networks of Power. AB - Departing from what has in medical anthropology been termed the individual body, the social body and body politics, actor-networks in medical pluralism are investigated on the basis of a study of complementary and alternative forms of medicine (CAM) in Denmark, including participant-observation in 12 clinics of reflexology, biopathy and kinesiology, as well as interviews and informal conversations with more than 40 alternative practitioners and 300 patients of CAM clinics. In this study, several actor-networks that connect metaphorical models of the body, clinical technology, social relations and political structures of the Danish society are revealed: a technocrat network, a social-democratic consultancy network and a neo-liberal network. The co-existence of several actor networks has phenomenological as well as structural implications. The implications for patients using several forms of therapy is important insofar as the patients' move between different actor-networks of healing implies switches between different experiences of body and self. Each of the actor-networks at the same time implies different positions in relation to the public healthcare system, and some actor-networks appear to be more compatible than others with the generalized and technical properties of public healthcare. PMID- 27268743 TI - 'Our Families are Killing Us': HIV/AIDS, Witchcraft and Social Tensions in the Caprivi Region, Namibia. AB - The importance of exploring 'indigenous' constructions of illness is vital when explanatory models of ill health differ markedly from dominant biomedical paradigms. In the Caprivi region of Namibia, an upsurge of witchcraft accusations can be seen as a direct reaction to increasing AIDS-related illness and deaths, and to changes in socio-economic attitudes and expectations. The mobilization of witchcraft narratives provides a socially acceptable explanation for illness, and can positively influence decisions regarding the care and identity of the ill person. However, drawing upon data collected at kin and village level, this paper demonstrates that while witchcraft accusations can avert stigma and blame away from the ill person, they can also result in significant disruption to livelihoods, and place considerable tension upon key social capital networks at a time when the household is particularly vulnerable. Such findings have significant implications for the effectiveness of HIV prevention and AIDS mitigation initiatives, and for livelihood security. PMID- 27268744 TI - Hope from Abroad in the International Medical Travel of Yemeni Patients. AB - Studies of care-seeking behaviour have generally focused only on the medical facilities that are available within a country's national boundaries. However, a growing number of patients worldwide are pursuing medical services outside of their own countries. The burgeoning literature on 'medical tourism' tends to offer the perspectives of the treatment destinations, not the experiences of patients. This paper examines the international medical travel of patients from the capital-poor country of Yemen. Families in Yemen often sacrifice greatly to seek the advanced, trustworthy technological medicine that is unavailable locally. The paper draws on interviews conducted with 71 Yemeni medical travellers in India and Jordan, as well as a survey of 205 doctors in Yemen about their disclosure practices regarding terminally ill patients. While perhaps an attractive option in today's global world, the use of medical services abroad affects local perceptions: it perpetuates a lack of trust in local capabilities, invites criticism of the government for not providing care to its citizens and fosters the hope that a cure exists somewhere in the world. PMID- 27268745 TI - Beyond Meaning: Globalization and the Icons of Power. AB - As the nature of symbolic mechanisms has been reconsidered, shared meaning in healing rituals can no longer be unproblematically assumed. Globalization processes challenge the idea of local worlds of meaning as foundational for healing. Discussing two episodes of healing in 'global assemblages', the paper questions the centrality of meaning in the healing encounter. In search for alternatives, it turns to the ethical phenomenology of Levinas. It is suggested that in the core of healing encounter lies 'the healing gesture' of the Other seen as an icon of power. PMID- 27268746 TI - Wrongdoing and Retribution: Children's Conceptions of Illness Causality in a Central Indian Village. AB - This paper is a study of children's conceptions of illness causality. Based on ethnographic research in a central Indian tribal community, it is a response to the lack of systematic attention within mainstream anthropology on children, and within medical anthropology on children's understanding of illness causation. A combination of participant observation and structured interviews was used to examine local distinctions between 'natural' and 'supernatural' illness, which are underpinned by ideas about supernatural retribution. The focus in this paper is on how children learn and reason about such ideas, and on the processes by which they assume culpability for 'supernatural' illnesses. By arguing that children do not simply replicate adult conceptions about illness causality but instead apply their own experience to their understanding and representation of such ideas, this paper challenges taken-for-granted assumptions about the acquisition and reproduction of cultural knowledge. PMID- 27268748 TI - Reply to Rejoinder: Examining the Complex Social Basis of Medical Decision Making. PMID- 27268747 TI - Rejoinder : Which Child will Live or Die in France. PMID- 27268749 TI - Prognostic Impact of Discordance in Hormone Receptor Status Between Primary and Recurrent Sites in Patients With Recurrent Breast Cancer. AB - INTRODUCTION: Recent retrospective studies have reported discordance rate of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) statuses between primary and recurrent tumors and prognostic values of discordance. However, the results of these reports may possibly include analytical error. PATIENTS AND METHODS: We analyzed 153 patients from whom pathological specimens of tumor tissues were available from both primary and recurrent sites. For all specimens, immunohistochemistry was performed for these statuses with a standardized method. Two experienced pathologists evaluated these specimens in a blinded fashion. RESULTS: The discordance rates for estrogen receptor, progesterone receptor, and HER2 were 18%, 26%, and 7%, respectively. Subtype changes based on HR and HER2 status occurred in 21% of patients. Clinical outcome was significantly worse in the patients with the tumors that were primarily HR-positive (HR(+)) converted to HR-negative (HR(-)) at recurrent sites than in the patients with the tumors in which HR status did not change or converted from HR(-) to HR(+) (P = .001). Clinical outcome was also significantly worse in the patients with the primarily HR(+) tumor that converted to triple negative in the recurrence sites than in the patients with a constantly HR(+) tumor (P < .001). By the Cox multivariate analyses, loss of HR expression and conversion to triple negative at the recurrence sites were independent indicators of worse clinical outcome. CONCLUSION: Discordance in HR and HER2 status often occurred between primary and recurrent breast cancer and had independent prognostic impact in the patients with recurrent breast cancer. PMID- 27268751 TI - Intramolecular, Exciplex-Mediated, Proton-Coupled, Charge-Transfer Processes in N,N-Dimethyl-3-(1-pyrenyl)propan-1-ammonium Cations: Influence of Anion, Solvent Polarity, and Temperature. AB - An intramolecular exciplex-mediated, proton-coupled, charge-transfer (PCCT) process has been investigated for a series of N,N-dimethyl-3-(1-pyrenyl)propan-1 ammonium cations with different anions (PyS) in solvents of low to intermediate polarity over a wide temperature range. Solvent mediates both the equilibrium between conformations of the cation that place the pyrenyl and ammonium groups in proximity (conformation C) or far from each other (conformation O) and the ability of the ammonium group to transfer a proton adiabatically in the PyS excited singlet state. Thus, exciplex emission, concurrent with the PCCT process, was observed only in hydrogen-bond accepting solvents of relatively low polarity (tetrahydrofuran, ethyl acetate, and 1,4-dioxane) and not in dichloromethane. From the exciplex emission and other spectroscopic and thermodynamic data, the acidity of the ammonium group in conformation C of the excited singlet state of PyS (pKa*) has been estimated to be ca. -3.4 in tetrahydrofuran. The ratios between the intensities of emission from the exciplex and the locally excited state (IEx/ILE) appear to be much more dependent on the nature of the anion than are the rates of exciplex formation and decay, although the excited state data do not provide a quantitative measure of the anion effect on the C-O equilibrium. The activation energies associated with exciplex formation in THF are calculated to be 0.08 to 0.15 eV lower than for the neutral amine, N,N-dimethyl-3-(1 pyrenyl)propan-1-amine. Decay of the exciplexes formed from the deprotonation of PyS is hypothesized to occur through charge-recombination processes. To our knowledge, this is the first example in which photoacidity and intramolecular exciplex formation (i.e., a PCCT reaction) are coupled. PMID- 27268750 TI - Classification, Treatment Strategy, and Associated Drug Resistance in Breast Cancer. AB - Breast cancer is the second leading cause of cancer death in women, affecting 1.7 million patients every year worldwide. As a result of its heterogeneous nature, the genetic profile and associated clinical feature varies greatly among different breast cancer subtypes. With the advancement of molecular biology, our understanding of breast cancer has improved greatly in recent years. In this review, we examine different types of breast cancer and summarize their clinical features, current treatment schemes, and potential drug resistance profiles in response to treatments. We believe that the understanding of the molecular mechanisms of each treatment and subsequent drug resistance development will eventually lead to the discovery of more effective and efficient second-line therapeutics. PMID- 27268752 TI - Active Components of Essential Oils as Anti-Obesity Potential Drugs Investigated by in Silico Techniques. AB - In this study, for the first time, we have considered essential oils (EOs) as possible resources of carbonic anhydrase inhibitors (CAIs), in particular against the mitochondrial isoform VA that, actually, represents an innovative target for the obesity treatment. In silico structure-based virtual screening was performed in order to speed up the identification of promising antiobesity agents. The potential hit compounds were submitted to in vitro assays and experimental results, corroborated by molecular modeling studies, showed EOs components as a new class of CAIs with a competitive mechanism of action due to the zinc ion coordination within the active sites of these metallo-enzymes. PMID- 27268753 TI - Connexin32 deficiency exacerbates carbon tetrachloride-induced hepatocellular injury and liver fibrosis in mice. AB - OBJECTIVE: Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce. METHODS: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers. RESULTS: More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels. CONCLUSION: These findings could suggest that connexin32 based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis. PMID- 27268754 TI - A new predictive tool for the early risk assessment of gestational diabetes mellitus. AB - AIMS: The Italian National Institute of Health has recently introduced a selective screening based on the risk profile of pregnant women, which while recommending against screening of women at low risk (LR) for GDM, it recommends an early test for women at high risk (HR) for GDM. Herein, we assessed the accuracy and cost-effectiveness of this screening and developed a new index that improves these requirements. METHODS: We retrospectively enrolled 3974 pregnant women. GDM was diagnosed with a 2h 75-g OGTT at 16-18 weeks (early test) or 24-28 weeks of gestation, according to the IADPSG guidelines. RESULTS: 55.6% of HR women had GDM, although only 38.4% underwent early screening. Among 2654 women at medium risk, 20.9% had GDM; paradoxically, among 770 LR women, that would not have been screened, 26.6% received a GDM diagnosis. Based on these unsatisfactory results, we elaborated the Capula's index, that reduced both screening tests (p<0.001) and potentially undetected GDM cases (p<0.001), and corrected the paradoxical prevalence estimates of GDM obtained with the current Italian guidelines. Also, Capula's index improved correlation of GDM risk profile with obstetric and neonatal adverse events. CONCLUSIONS: Capula's index improves accuracy of selective screening for GDM. PMID- 27268755 TI - Development of high-throughput multi-residue method for non-steroidal anti inflammatory drugs monitoring in swine muscle by LC-MS/MS. AB - A reliable and simple method for the detection and quantification of residues of 14 non-steroidal anti-inflammatory drugs and a metamizole metabolite in swine muscle was developed using liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). The samples were extracted with acetonitrile (ACN) in solid-liquid extraction followed by a low-temperature partitioning (LLE LTP) process at -20 +/- 2 degrees C. After evaporation to dryness, the residue was reconstituted with hexane and a mixture of water:acetonitrile (1:1). LC separation was achieved on a reversed-phase (RP18) column with gradient elution using water (phase A) and ACN (phase B) both containing 1 mmol l(-)(1) ammonium acetate (NH4COO) with 0.025% acetic acid. Analysis was carried out on a triple quadrupole tandem mass spectrometer (LC-MS/MS) in multiple reaction monitoring mode using an electrospray interface in negative and positive mode in a single run. Method validation was performed according to the criteria of Commission Decision No. 2002/657/EC. The matrix effect and linearity were evaluated. Decision limit (CCalpha), detection capability (CCbeta), accuracy and repeatability of the method are also reported. The proposed method proved to be simple, easy and adequate for high-throughput analysis and was applied to routine analysis by the Brazilian Ministry of Agriculture, Livestock and Food Supply. PMID- 27268756 TI - Characteristics of bioavailable organic phosphorus in sediment and its contribution to lake eutrophication in China. AB - This study aims to establish the relative importance of sediment organic phosphorus (Po) to the total P and the major classes of organic molecules that contribute to sediment Po, determined by measuring their susceptibility to enzymatic hydrolysis, across a suite of lakes ranging from oligotrophic to eutrophic status. The results showed that Po accounted for 21-60% of total P, and bioavailable Po accounted for 9-34% of Po in the sediments. The bioavailable Po includes mainly labile (H2O-Po) and moderately labile (NaOH-Po) P forms. For H2O Po (accounting for only1.4% of Po), 53% (average) was labile monoester P, 28% was diester P and 17% was phytate-like P. For NaOH-Po (accounting for 9-33% of Po), 32% was labile monoester P, 33% was phytate-like P and 18% was diester P. The composition of bioavailable Po, determined by enzyme assays, was related to the lake nutrient levels, which implies that sediment bioavailable Po could act as an effective indicator for lake eutrophic status. With the increase of lake nutrient levels, bioavailable Po content and alkaline phosphatase activity in the sediment all increased, indicating that Po represents an important and bioavailable source of P that increases with eutrophication, and could contribute to internal loading and resistance of eutrophic lakes to remediation. This implies that eutrophic lakes would maintain long-term eutrophic status and algal bloom phenomena even after the external input of P was controlled and the total P concentration of water has declined. Thus, in order to reduce the release risk of sediment P more efficiently and effectively, sediment P control technique should focus not only on reducing the total P and inorganic P, but should also pay close attention to the removal of bioavailable Po. PMID- 27268757 TI - Pediatric Nerve Biopsy Diagnostic and Treatment Utility in Tertiary Care Referral. AB - BACKGROUND: Pediatric neuropathies are both unique and similar to their adult counterparts, with genetic varieties thought to be more common. The objective of this work was to assess the utility of nerve biopsy in children at a tertiary referral center in light of availability of current genetic testing. METHODS: We retrospectively reviewed the clinical, nerve biopsy, and genetic testing findings of 316 pediatric (age <=18 years) patients. RESULTS: Median age at diagnosis was 9.8 years (4 days to 18 years). Nerve biopsy was nontargeted in 198 (182 whole sural, seven superficial peroneal, and nine other), targeted in 21 (14 fascicular sciatic and seven brachial plexus), and unknown in 97 cases. Prebiopsy localizations and diagnoses were diverse, most commonly with length-dependent localizations (n = 150). Median follow-up was 6 months (0 to 480 months). A distinctive histopathologic diagnosis was made in 106 cases (33%), including inflammatory or immune (n = 30), neoplastic (n = 19), hereditary (n = 41), vasculitis (n = 10), and other (n = 6). Nerve biopsy confirmed the suspected diagnosis in 91 (29%) individuals and changed or refined the initial diagnosis in 182 (58%). Treatment modifications as a result of biopsy occurred in 80 (25%) cases; 59 (19% of the entire cohort) with clinical improvements noted, most commonly by immunotherapy (n = 30). Low diagnostic yield occurred in "hypotonic infants" without nerve conduction abnormalities. Pain at the biopsy site beyond 1 month was rare (n = 3; 1%). Forty-four patients underwent genetic testing. Among demyelinating varieties, mutations were identified in five of 11 (46%) cases compared with only six of 33 (18%) cases of axonal varieties. CONCLUSION: Pediatric nerve biopsy provides diagnostic information that frequently alters treatment recommendations. Furthermore, it leads to clinical improvements, especially in inflammatory immune neuropathies. For suspected inherited varieties, genetic testing has the highest diagnostic yield in demyelinating phenotypes. PMID- 27268759 TI - Telomeric Region of the Spinal Muscular Atrophy Locus Is Susceptible to Structural Variations. AB - BACKGROUND: Most patients with spinal muscular atrophy lack the survival motor neuron 1 gene (SMN1) in the telomeric region of the spinal muscular atrophy locus on chromosome 5q13. On the other hand, the copy number of SMN2, a centromeric homolog of SMN1, is increased in many of these patients. This study aimed to clarify the mechanism underlying these structural variations. METHODS: We determined the copy numbers of telomeric and centromeric genes in the spinal muscular atrophy locus of 86 patients and 22 control subjects using multiplex ligation-dependent probe amplification analysis. Then, we chose 74 patients lacking SMN1 exons 7 and 8, and compared their dataset with that of 22 control subjects retaining SMN1 exons 7 and 8. RESULTS: The SMN2 copy number was shown to vary widely and to correlate with the disease severity of the patients. Interestingly, telomeric NAIP and telomeric GTF2H2 showed similar tendencies. We also noted positive correlations among the copy number of SMN2 and the telomeric genes of the spinal muscular atrophy locus. However, the copy numbers of centromeric NAIP and centromeric GTF2H2 were stable among the patients, with both approximating a value of two. CONCLUSION: Our findings suggested that the telomeric region of the spinal muscular atrophy locus appears to be susceptible to structural variation, whereas the centromeric region is stable. Moreover, according to our results, new SMN2 copies may be generated in the telomeric region of the spinal muscular atrophy locus, supporting the SMN1-to-SMN2 gene conversion theory. PMID- 27268760 TI - A Cross-sectional Survey of Growth and Nutritional Status in Children With Cerebral Palsy in West China. AB - BACKGROUND: We describe the growth and nutritional status of children with cerebral palsy (2 to 18 years old) in West China and to explore the correlation between the nutritional status and age, gender, and gross and fine motor function. METHODS: We performed a cross-sectional survey of children registered as having cerebral palsy in the China Disabled Persons' Federation branch in Chengdu. Growth (height and weight) and nutritional (body mass index) status were recorded. Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) were used to determine gross and fine motor function, respectively. The association between nutritional status and age, GMFCS and MACS levels was evaluated. RESULTS: We enrolled 377 children (53.6% male), among whom 160 (42.4%) were stunting, 48 (12.7%) underweight, 81 (21.5%) thin, and 70 (18.5%) overweight and obese. Thinness was the main nutritional problem in older patients (12 to 18 years), whereas overweight and obesity were the major issues in younger patients (2 to 12 years). Growth deviation and malnutrition were significantly more prevalent in patients with severe motor impairments. A significant negative correlation was found between nutritional status and age, GMFCS and MACS levels, and between growth and GMFCS and MACS levels. CONCLUSIONS: Growth abnormality is common in children with cerebral palsy. Malnutrition and overnutrition both exist in children with cerebral palsy. Characteristics at different age stages and motor functional levels should be taken into consideration in the management of growth and nutrition in this population. PMID- 27268758 TI - Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research. AB - Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine birthmark) of the forehead or upper eyelid which can signal an increased risk of brain and/or eye involvement prior to the onset of specific symptoms. This symptom-free interval represents a time when a targeted intervention could help to minimize the neurological and ophthalmologic manifestations of the disorder. This paper summarizes a 2015 SWS workshop in Bethesda, Maryland that was sponsored by the National Institutes of Health. Meeting attendees included a diverse group of clinical and translational researchers with a goal of establishing research priorities for the next few years. The initial portion of the meeting included a thorough review of the recent genetic discovery and what is known of the pathogenesis of SWS. Breakout sessions related to neurology, dermatology, and ophthalmology aimed to establish SWS research priorities in each field. Key priorities for future development include the need for clinical consensus guidelines, further work to develop a clinical trial network, improvement of tissue banking for research purposes, and the need for multiple animal and cell culture models of SWS. PMID- 27268761 TI - Worsening of Seizures After Asparagine Supplementation in a Child with Asparagine Synthetase Deficiency. AB - OBJECTIVE: Asparagine synthetase deficiency is an autosomal recessive neurometabolic disorder characterized clinically by severe congenital microcephaly, global developmental delay, intractable epilepsy, and motor impairment in the form of spastic quadriparesis. Diagnosis is confirmed by findings of low cerebral spinal fluid or plasma asparagine in addition to a mutation of the subsequently in ASNS gene. There is no documented trial of asparagine as a treatment for this disorder. PATIENT DESCRIPTION: We present a child with asparagine synthetase deficiency whose mental status improved slightly from a vegetative state to a minimally conscious state after starting asparagine supplementation. He subsequently became irritable, developed sleep disturbance, and experienced worsening seizures, requiring discontinuation of the asparagine supplements. CONCLUSIONS: Asparagine supplementation may be not effective in controlling the seizures in asparagine synthetase deficiency, and it is likely to make them worse. PMID- 27268762 TI - Acute Infantile Encephalopathy as Presentation of Succinic Semialdehyde Dehydrogenase Deficiency. AB - BACKGROUND: Succinic semialdehyde dehydrogenase deficiency is a rare neurological disorder resulting from impaired gamma-aminobutyric acid metabolism. The syndrome typically presents as a static encephalopathy with developmental delays, hypotonia, and seizures. METHODS: A six-month-old previously healthy girl developed acute choreoathetosis and severe hypotonia in the setting of influenza A infection. In our database of 112 patients with succinic semialdehyde dehydrogenase deficiency, one additional patient was identified who presented with an acute illness (encephalopathy associated with bronchiolitis at age five months). RESULTS: Urine organic acid and cerebrospinal fluid analyses confirmed elevated 4-hydroxybutyric acid in both cases, verified by enzymatic quantification in lymphocytes in the second patient. Brain magnetic resonance imaging scans in both cases showed bilateral symmetric T2 hyperintensities of globus pallidi. The lesions demonstrated restricted diffusion, consistent with acute symptom onset. CONCLUSIONS: In contrast to most organic acidopathies, succinic semialdehyde dehydrogenase deficiency typically presents with nonprogressive global developmental delays. Here we report that succinic semialdehyde dehydrogenase deficiency can present fulminantly during a febrile illness as well as in the more common static fashion, thereby broadening the spectrum of onset patterns in this disorder. PMID- 27268763 TI - Posterior Reversible Encephalopathy Syndrome Associated With Licorice Consumption: A Case Report in a 10-Year-Old Boy. Pediatric Neurology 2015;52(4):457-459. PMID- 27268764 TI - Rub Evoked Reflex Epilepsy in an Infant With Cerebellar Hypoplasia. PMID- 27268765 TI - Canadian student leaders' perspective on interprofessional education: A consensus statement. AB - The purpose of this article is to report on the outcomes of an interprofessional education (IPE) consensus-building exercise amongst student leaders enrolled in health science-related degree programs. The 12 participants included undergraduate and graduate students from eight different universities situated in five Canadian provinces. Their areas of study spanned a broad range of professions and disciplines including child and youth care, health promotion, nursing, kinesiology, medicine, physical education, psychology, and social work. A consensus statement regarding IPE and, more specifically, "what we know," "what we don't know," and "where do we go from here" is presented. These insights are unique, and a willingness to embrace them may be critical in building the next generation of improved IPE offerings across the country. PMID- 27268766 TI - ABCB1 1199G>A polymorphism (rs2229109) affects the transport of imatinib, nilotinib and dasatinib. AB - AIM: ABCB1 (or P-glycoprotein) is implicated in the multidrug-resistance phenotype, including the resistance toward anticancer drugs such as tyrosine kinase inhibitors (TKIs). The purpose of this study was to evaluate in vitro the influence of the ABCB1 1199G>A SNP on ABCB1 transport activity toward selected TKIs (imatinib, nilotinib and dasatinib) that are currently used in chronic myelogenous leukemia. MATERIAL & METHODS: Two different cell lines, HEK293 and K562, were stably transfected with ABCB1 1199G wild-type or ABCB1 1199A variant allele. The impact of this polymorphism on accumulation and antiproliferative effects of imatinib, nilotinib and dasatinib was evaluated. RESULTS: In K562 models, the expression of Asn400 variant protein was associated with lower antiproliferative effects of imatinib, nilotinib and dasatinib compared with Ser400 wild-type protein. Moreover, in HEK293 cells, imatinib and nilotinib intracellular accumulation were lower in variant compared with wild-type models. CONCLUSION: Imatinib, nilotinib and dasatinib are transported more efficiently by the ABCB1 variant (Asn400) compared with the wild-type (Ser400) protein. The impact of ABCB1 1199G>A SNP on TKI response should be further investigated in chronic myelogenous leukemia patients. PMID- 27268767 TI - Determining the temporal development of dentin-composite bond strength during curing. AB - OBJECTIVES: As composite restorations cure a competition develops between bond formation and shrinkage stress at the composite-dentin interface. Thus, understanding the temporal development of tooth-composite bond strength should enable better assessment of tooth-composite debonding. METHODS: In this study, bond strengths of composite-dentin specimens obtained from tensile test at different curing times were used to determine the bond formation rate. By varying the composite thickness and output from the curing light, their effects on the rate of bond formation for two different materials (a conventional and a bulk fill composite) were also investigated. The proportions of cohesive and adhesive failure were determined by analysis of electron micrographs of the fractured surfaces. RESULTS: The development of dentin-composite bond strength (S) with time (t) can be described by the equation: S=Smax(1-exp(-alphat)), where Smax is the final bond strength (~12MPa for both composites) and alpha the rate of bond formation. Using bulk-fill and thinner specimens gave faster bond formation. In fact, the higher the irradiance at the interface, the higher the rate of bond formation. However, alpha had a maximum value of ~0.6s(-1) and the rule of reciprocity did not hold. A minimum dose of ~2J/cm(2) was required to achieve adequate bond strength. The predominant failure mode changed from cohesive in the composite and adhesive to interfacial at the adhesive-dentin interface, indicating the latter to be the weakest link in the cured dentin-composite assemblies considered. SIGNIFICANCE: When combined with the temporal development of shrinkage stress, the current results will help determine the likelihood of tooth-composite debonding. PMID- 27268769 TI - Morphological and Functional Evaluation of Meibomian Gland Dysfunction in Rosacea Patients. PMID- 27268768 TI - Bystander Attitudes to Prevent Sexual Assault: A Study of College Students in the United States, Japan, India, Vietnam, and China. AB - College women are at a high risk of sexual assault. Although programs that aim to change bystander behaviors have been shown to be potentially effective in preventing sexual assault on campuses in the United States, little is known about bystander behaviors outside of the United States. The purpose of this study was to explore and compare factors affecting bystander behaviors regarding sexual assault intervention and prevention among undergraduate students in the United States, Japan, India, Vietnam, and China. A total of 1,136 students participated in a self-reported survey. Results demonstrate substantial variations across countries. Bystander behaviors are associated with multilevel factors, including gender, knowledge of individuals who have experienced a sexual assault, and knowledge about campus or community organizations. PMID- 27268770 TI - Tunable Electrical Conductivity and Magnetic Property of the Two Dimensional Metal Organic Framework [Cu(TPyP)Cu2(O2CCH3)4]. AB - The coordination chemistry between copper acetate [Cu2(OAc)4] and 5,10,15,20 tetra-4-pyridyl-21H,23H-porphine (porphyrin, H2TPyP) is found to give rise to either a 2D metal-organic framework (MOF) [Cu(TPyP)Cu2(O2CCH3)4] or a 3D MOF [Cu(TPyP)CuCl2].2.5TCE.7H2O], depending on the choice of solvent. The 2D MOF can be made into a film, which was doped with 7,7,8,8-tetracyanoquinodimethane (TCNQ), and the electrical conductivity of the thin film was increased by 3 orders of magnitude with respect to that of the undoped Cu-MOF. The formation of a charge-transfer complex between TCNQ and the 2D Cu-MOF also imparts stronger paramagnetic properties than for the undoped MOF. PMID- 27268776 TI - [Traumatic superior orbital fissure syndrome: Update]. AB - The traumatic superior orbital fissure syndrome is an uncommon complication of craniomaxillofacial trauma. The diagnosis is clinical and associates ophtalmoplegia (constantly at initial clinical examination), ptosis and anaesthesia of the forehead. Young men victim of road traffic accidents are most often affected. CT-scan usually shows facial and/or craniofacial fractures more or less spreading towards the superior orbital fissure. The absence of fracture seen at the X-rays does not eliminate the diagnosis. Initial management should be multidisciplinary (maxillofacial surgeons, ophthalmologists and neurosurgeons) and conducted early if possible. It combines high-dose corticosteroids and decompression surgery if necessary. Abstention may be indicated in cases of delayed diagnosis with spontaneous improvement. Symptoms improve early but follow up should be extended over several months given the recovery time. PMID- 27268777 TI - Microenvironment of macula flava in the human vocal fold as a stem cell niche. AB - BACKGROUND: There is growing evidence that the cells in the maculae flavae are tissue stem cells of the human vocal fold mucosa, and that the maculae flavae are a candidate for a stem cell niche. The role of microenvironment in the maculae flavae of the human vocal fold mucosa was investigated. METHOD: Anterior maculae flavae from six surgical specimens were cultured in a mesenchymal stem cell growth medium or a Dulbecco's modified Eagle's medium. RESULTS: Using mesenchymal stem cell growth medium, the subcultured cells formed a colony-forming unit, and cell division reflected asymmetric self-renewal. This indicates that these cells are mesenchymal stem cells or stromal stem cells in the bone marrow. Using Dulbecco's modified Eagle's medium, the subcultured cells showed symmetric cell division without a colony-forming unit. CONCLUSION: A proper microenvironment in the maculae flavae of the human vocal fold mucosa is necessary to be effective as a stem cell niche that maintains the stemness of the contained tissue stem cells. PMID- 27268778 TI - Extrapolating theoretical efficacy of inactivated influenza A/H5N1 virus vaccine from human immunogenicity studies. AB - Influenza A virus subtype H5N1 has been a public health concern for almost 20years due to its potential ability to become transmissible among humans. Phase I and II clinical trials have assessed safety, reactogenicity and immunogenicity of inactivated influenza A/H5N1 virus vaccines. A shortage of vaccine is likely to occur during the first months of a pandemic. Hence, determining whether to give one dose to more people or two doses to fewer people to best protect the population is essential. We use hemagglutination-inhibition antibody titers as an immune correlate for avian influenza vaccines. Using an established relationship to obtain a theoretical vaccine efficacy from immunogenicity data from thirteen arms of six phase I and phase II clinical trials of inactivated influenza A/H5N1 virus vaccines, we assessed: (1) the proportion of theoretical vaccine efficacy achieved after a single dose (defined as primary response level), and (2) whether theoretical efficacy increases after a second dose, with and without adjuvant. Participants receiving vaccine with AS03 adjuvant had higher primary response levels (range: 0.48-0.57) compared to participants receiving vaccine with MF59 adjuvant (range: 0.32-0.47), with no observed trends in primary response levels by antigen dosage. After the first and second doses, vaccine with AS03 at dosage levels 3.75, 7.5 and 15mcg had the highest estimated theoretical vaccine efficacy: Dose (1) 45% (95% CI: 36-57%), 53% (95% CI: 42-63%) and 55% (95% CI: 44 64%), respectively and Dose (2) 93% (95% CI: 89-96%), 97% (95% CI: 95-98%) and 97% (95% CI: 96-100%), respectively. On average, the estimated theoretical vaccine efficacy of lower dose adjuvanted vaccines (AS03 and MF59) was 17% higher than that of higher dose unadjuvanted vaccines, suggesting that including an adjuvant is dose-sparing. These data indicate adjuvanted inactivated influenza A/H5N1 virus vaccine produces high theoretical efficacy after two doses to protect individuals against a potential avian influenza pandemic. PMID- 27268779 TI - One year in review 2016: novelties in the treatment of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic disease characterised by inflammation of the synovial tissue in joints, which can lead to joint destruction. The primary goal of the treatment is to control pain and inflammation, reduce joint damage and disability, and maintain or improve physical function and quality of life. The present review is aimed at providing a critical analysis of the recent literature on the novelties in the treatment of RA, with a particular focus on the most relevant studies published over the last year. PMID- 27268780 TI - Juvenile eosinophilic fasciitis: three case reports with review of the literature. AB - OBJECTIVES: Eosinophilic fasciitis is an uncommon scleroderma-like disorder characterised by induration and thickening of skin and soft tissue, usually associated with peripheral eosinophilia, poorly characterised in childhood. METHODS: We report 3 paediatric cases of eosinophilic fasciitis showing unusual clinical and histopathological features with a review of the literature. RESULTS: All cases presented progressive motility impairment started from upper limbs with no skin abnormalities. All cases showed systemic inflammatory involvement and 2 patients had acute complications. Two patients developed disabling outcomes despite appropriate treatments. CONCLUSIONS: Eosinophilic fasciitis may present unusual clinical and histopathological features during childhood and requires early recognition in order to prevent acute complications and disabling outcomes. PMID- 27268781 TI - Nickel-Catalyzed Reductive Cross-Coupling of Benzyl Chlorides with Aryl Chlorides/Fluorides: A One-Pot Synthesis of Diarylmethanes. AB - The first nickel-catalyzed, magnesium-mediated reductive cross-coupling between benzyl chlorides and aryl chlorides or fluorides is reported. A variety of diarylmethanes can be prepared in good to excellent yields in a one-pot manner using easy-to-access mixed PPh3/NHC Ni(II) complexes of Ni(PPh3)(NHC)Br2 (NHC = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, IPr, 1a; 1,3-di-tert butylimidazol-2-ylidene, ItBu, 1b) as catalyst precursors. Activation of polychloroarenes or chemoselective cross-coupling based on the difference in catalytic activity between 1a and 1b is used to construct oligo-diarylmethane motifs. PMID- 27268782 TI - Insecticide chlorpyrifos and fungicide carbendazim, common food contaminants mixture, induce hepatic, renal, and splenic oxidative damage in female rats. AB - The fungicide carbendazim (CBZ) and insecticide chlorpyrifos (CPF) are currently applied together by farmers for the control of pests. Here, we investigated the impacts of 7 days oral co-exposure to 10 mg/kg body weight of CPF and 50 mg/kg body weight of CBZ on selected oxidative stress and antioxidant biomarkers in the liver, kidney, and spleen of female rats. The results showed that while the body weight gain and relative organ weights were not significantly affected after separate exposure to CPF and CBZ, there was a significant decrease in the body weight gain with concomitant increases in the relative kidney and spleen weights of rats treated with the mixture. Also, CPF and CBZ co-exposure significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine ( p < 0.05) when compared with the groups treated with CBZ or CPF alone and the control. The significant decreases in both antioxidant enzymes activities and nonenzymatic antioxidant level following individual administration of CPF and CBZ to rats were intensified in the co-exposure group ( p < 0.05). Additionally, the marked increases in the levels of oxidative stress indices in liver, kidney, and spleen of rats treated with CPF or CBZ alone were intensified in the co-exposure group ( p < 0.05). Histopathologically, co-exposure to CPF and CBZ exacerbates their individual effects on the liver, kidney, and spleen. These findings showed that co-exposure to CPF and CBZ in rats elicited more severe oxidative damage on the liver, kidney, and spleen of the rats, indicative of an additive effect compared to CPF or CBZ alone and as such, may pose a greater environmental risk to humans. PMID- 27268783 TI - Electrically Responsive Surfaces: Experimental and Theoretical Investigations. AB - Stimuli-responsive surfaces have sparked considerable interest in recent years, especially in view of their biomimetic nature and widespread biomedical applications. Significant efforts are continuously being directed at developing functional surfaces exhibiting specific property changes triggered by variations in electrical potential, temperature, pH and concentration, irradiation with light, or exposure to a magnetic field. In this respect, electrical stimulus offers several attractive features, including a high level of spatial and temporal controllability, rapid and reverse inducement, and noninvasiveness. In this Account, we discuss how surfaces can be designed and methodologies developed to produce electrically switchable systems, based on research by our groups. We aim to provide fundamental mechanistic and structural features of these dynamic systems, while highlighting their capabilities and potential applications. We begin by briefly describing the current state-of-the-art in integrating electroactive species on surfaces to control the immobilization of diverse biological entities. This premise leads us to portray our electrically switchable surfaces, capable of controlling nonspecific and specific biological interactions by exploiting molecular motions of surface-bound electroswitchable molecules. We demonstrate that our self-assembled monolayer-based electrically switchable surfaces can modulate the interactions of surfaces with proteins, mammalian and bacterial cells. We emphasize how these systems are ubiquitous in both switching biomolecular interactions in highly complex biological conditions while still offering antifouling properties. We also introduce how novel characterization techniques, such as surface sensitive vibrational sum-frequency generation (SFG) spectroscopy, can be used for probing the electrically switchable molecular surfaces in situ. SFG spectroscopy is a technique that not only allowed determining the structural orientation of the surface-tethered molecules under electroinduced switching, but also provided an in-depth characterization of the system reversibility. Furthermore, the unique support from molecular dynamics (MD) simulations is highlighted. MD simulations with polarizable force fields (FFs), which could give proper description of the charge polarization caused by electrical stimulus, have helped not only back many of the experimental observations, but also to rationalize the mechanism of switching behavior. More importantly, this polarizable FF-based approach can efficiently be extended to light or pH stimulated surfaces when integrated with reactive FF methods. The interplay between experimental and theoretical studies has led to a higher level of understanding of the switchable surfaces, and to a more precise interpretation and rationalization of the observed data. The perspectives on the challenges and opportunities for future progress on stimuli-responsive surfaces are also presented. PMID- 27268784 TI - Gating, Regulation, and Structure in K2P K+ Channels: In Varietate Concordia? AB - K2P K(+) channels with two pore domains in tandem associate as dimers to produce so-called background conductances that are regulated by a variety of stimuli. Whereas gating in K2P channels has been poorly understood, recent developments have provided important clues regarding the gating mechanism for this family of proteins. Two modes of gating present in other K(+) channels have been considered. The first is the so-called activation gating that occurs by bundle crossing and the splaying apart of pore-lining helices commanding ion passage. The second mode involves a change in conformation at the selectivity filter (SF), which impedes ion flow at this narrow portion of the conduction pathway and accounts for extracellular pH modulation of several K2P channels. Although some evidence supports the existence of an activation gate in K2P channels, recent results suggest that perhaps all stimuli, even those sensed at a distant location in the protein, are also mediated by SF gating. Recently resolved crystal structures of K2P channels in conductive and nonconductive conformations revealed that the nonconductive state is reached by blockade by a lipid acyl chain that gains access to the channel cavity through intramembrane fenestrations. Here we discuss whether this novel type of gating, proposed so far only for membrane tension gating, might mediate gating in response to other stimuli or whether SF gating is the only type of opening/closing mechanism present in K2P channels. PMID- 27268785 TI - Rare case of stress cardiomyopathy due to intramuscular epinephrine administration. AB - We report a case of a 37-year-old woman who presented to our hospital with retrosternal chest pain following intramuscular administration of epinephrine due to presumed anaphylaxis. On arrival, she was found to have ST segment depression in the anterolateral leads on ECG and elevated cardiac troponins. She was diagnosed with stress cardiomyopathy based on left ventricle dysfunction and angiographically normal coronary arteries on cardiac catheterisation. To the best of our knowledge, this is the third reported case of takotsubo cardiomyopathy following appropriately dosed intramuscular administration of epinephrine for anaphylaxis. This case highlights the importance of considering stress cardiomyopathy in patients presenting with chest pain syndrome following systemic administration of epinephrine. PMID- 27268787 TI - Pedunculated Epibulbar Osseous Choristoma in a Newborn. PMID- 27268786 TI - The Impact of Echocardiographic Screening for Rheumatic Heart Disease on Patient Quality of Life. AB - OBJECTIVE: To assess the impact of rheumatic heart disease (RHD) on child reported health-related quality of life (HRQOL) in the context of a Ugandan school-based echocardiographic screening program. Echocardiography-based screening has emerged as a tool for the early detection of RHD, but little is known about its impact on those screened. STUDY DESIGN: Participants included 358 children from Gulu and 28 children from Kampala Uganda. The Pediatric Quality of Life Inventory Version 4.0 was used to assess HRQOL in 4 groups of children: Gulu prescreen, Gulu postscreen, Gulu previously linked to care, and Kampala previously linked to care. Children in the pre- and postscreen groups were selected from a single school before and after screening occurred and matched by age and sex. Children previously linked to care were recruited from previous screening studies. RESULTS: When the echocardiogram was normal, there was no difference in HRQOL in the prescreen and postscreen groups. In the postscreen group, identification of latent RHD resulted in lower physical (75.3 vs 68.3, P = .03) and emotional (71.7 vs 63.4, P < .01) HRQOL, despite a lack of symptoms. The Kampala group had longer linkage to care (42 months vs 6 months, P < .01) and demonstrated greater HRQOL scores compared with the Gulu-linked group (70.7 vs 77.8, P < .01) and the combined Gulu cohort (77.8 vs 69.4, P = .02). CONCLUSIONS: Echocardiography-based screening for RHD does not diminish HRQOL in Ugandan children; rather, a diminished HRQOL score may be associated with being identified as RHD positive. Further investigation is needed to understand if longer linkage to care may ultimately normalize or improve HRQOL. PMID- 27268788 TI - UK rate of avoidable deaths is higher than EU average. PMID- 27268789 TI - Surgery for obese people with diabetes could save the NHS L100 000 a patient, finds study. PMID- 27268790 TI - Sub-lethal effects and bioconcentration of the human pharmaceutical clotrimazole in rainbow trout (Oncorhynchus mykiss). AB - The aim of this study was to characterize biomarker responses, haematological profiles, structural changes and uptake in juvenile rainbow trout exposed to clotrimazole (CLO) at three concentrations (0.01 - [lowest environmentally relevant concentration], 1.0 [highest environmentally relevant concentration] and 10 MUg L(-1)) in a semi-static system over a period of 42 days. Antioxidant defence enzymes, which responded to CLO exposure, changed the oxidative stress status of cells, but no differences were observed in lipid peroxidation. Clotrimazole triggered a biphasic response of CYP3A-like activity in liver microsomes, which may indicate a detoxification process in the liver. Histopathological alterations were most pronounced in kidneys and testes in the group exposed to 10 MUg L(-1). Structural changes in the kidney included tubulonephrosis and hyaline droplet degeneration in the tubular epithelial cells. The relative proportions of germ cells in testes were changed: The number of spermatozoa was reduced, and the spermatogonia and spermatocytes were increased. The highest CLO concentration was detected in fish liver (3710 ng per gram wet tissue) and kidney (4280 ng per gram wet tissue). Depuration half-life was estimated to be 72, 159, and 682 h in liver, muscle, and kidney, respectively. Taken together, these results provide valuable toxicological data on the effects of CLO on aquatic non-target organisms, which could be useful for further understanding of the potential risks in the real aquatic environment. PMID- 27268791 TI - Removal of phosphate using iron oxide nanoparticles synthesized by eucalyptus leaf extract in the presence of CTAB surfactant. AB - This study investigated the use of cetyltrimethylammonium bromide (CTAB) as a stabilizer in green synthesis to improve the reactivity of iron oxide nanoparticles (IONP). Results show that efficiency in removing phosphate increased from 71.0% to 97.3%. To understand how to improve the reactivity of IONP by CTAB: firstly, characterizations of IONP before and after phosphate removal by SEM, EDS, FTIR, XPS show the adsorption of P onto the IONP; secondly, batch experiments indicate that the adsorption capacity of phosphate increased when temperature or initial phosphate concentration increased and decreased with an increase in both adsorbent dose and pH. Adsorption followed the pseudo-second order kinetics model and the equilibrium data fitted well to the Langmuir isotherm. Thermodynamic data confirmed the spontaneous and endothermic nature of the adsorption process. Finally, it was proposed that the adsorption of phosphate using CTAB-modified IONP was mainly associated with inner-sphere complexing mechanism and electrostatic attraction. PMID- 27268792 TI - Resistance and uptake of cadmium by yeast, Pichia hampshirensis 4Aer, isolated from industrial effluent and its potential use in decontamination of wastewater. AB - Pichia hampshirensis 4Aer is first ever used yeast for the bioremediation of environmental cadmium (Cd(+2)) which could maximally remove 22 mM/g and 28 mM/g Cd(+2) from aqueous medium at lab and large scales, respectively. The biosorption was found to be the function of temperature, pH of solution, initial Cd(+2) concentration and biomass dosage. Competitive biosorption was investigated in binary and multi-metal system which indicated the decrease in Cd(+2) biosorption with increasing the competitive metal ions attributed to their higher electronegativity and larger radius. FTIR analysis revealed the active participation of amide and carbonyl moieties in Cd(+2) adsorption confirmed by EDX analysis. Electron micrographs summoned further surface adsorption and increased cell size due to intracellular Cd(+2) accumulation. Cd(+2) was the causative agent of some metal binding proteins as well as prodigious increase in glutathione and other non-protein thiols levels which is the crucial for the yeast to thrive oxidative stress generated by Cd(+2). Our experimental data were consistent with Langmuir as well as Freundlich isotherm models. The yeast obeyed pseudo second order kinetic model which makes it an effective biosorbent for Cd(+2). High bioremediation potential and spontaneity and feasibility of the process make P. hampshirensis 4Aer an impending foundation for green chemistry to exterminate environmental Cd(+2). PMID- 27268793 TI - Biocatalysis mechanism for p-fluoronitrobenzene degradation in the thermophilic bioelectrocatalysis system: Sequential combination of reduction and oxidation. AB - To verify the potentially synthetic anodic and cathodic biocatalysis mechanism in bioelectrocatalysis systems (BECSs), a single-chamber thermophilic bioelectrocatalysis system (R3) was operated under strictly anaerobic conditions using the biocathode donated dual-chamber (R1) and bioanode donated dual-chamber (R2) BECSs as controls. Direct bioelectrocatalytic oxidation was found to be infeasible while bioelectrocatalytic reduction was the dominant process for p Fluoronitrobenzene (p-FNB) removal, with p-FNB removal of 0.188 mM d(-1) in R1 and 0.182 mM d(-1) in R3. Cyclic voltammetry experiments confirmed that defluorination in the BECSs was an oxidative metabolic process catalyzed by bioanodes following the reductive reaction, which explained the 0.034 mM d(-1) defluorination in R3, but negligible defluorination in controls. Taken together, these results revealed a sequentially combined reduction and oxidation mechanism in the thermophilic BECS for p-FNB removal. Moreover, the enrichment of Betaproteobacteria and uniquely selected Bacilli in R3 were probably functional populations for p-FNB degradation. PMID- 27268794 TI - Enantioselective toxic effects of cyproconazole enantiomers against Chlorella pyrenoidosa. AB - Enantioselectivity in ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to Chlorella pyrenoidosa was studied. The 96h-EC50 values of rac- and the four enantiomers were 9.005, 6.616, 8.311, 4.290 and 9.410 mg/L, respectively. At the concentrations of 8 mg/L and 14 mg/L, the contents of pigments exposed in rac-, enantiomer-2 and 4 were higher than that exposed in enantiomer-1 and 3. The superoxide dismutase (SOD) and catalase (CAT) activity of algae exposed to enantiomer-1 and 3 was higher than that exposed to the rac-, enantiomer-2 and 4 at three levels. In addition, the malondialdehyde (MDA) concentrations in algae disposed with enantiomer-1 and 3 were increased remarkably at three levels. For the digestion experiment, the half-lives of four enantiomers in algae suspension were 28.06, 19.10, 21.13, 15.17 days, respectively. During the uptake experiment, the order of the concentrations of cyproconazole in algae cells was enantiomer-4, 2, 3 and 1. Based on these data, we concluded that ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to C. pyrenoidosa were enantioselective, and such enantiomeric differences must be taken into consideration when assessing the risk of cyproconazole to environment. PMID- 27268850 TI - Numerical assessment of a criterion for the optimal choice of the operative conditions in magnetic nanoparticle hyperthermia on a realistic model of the human head. AB - PURPOSE: This paper presents a numerical study aiming at assessing the effectiveness of a recently proposed optimisation criterion for determining the optimal operative conditions in magnetic nanoparticle hyperthermia applied to the clinically relevant case of brain tumours. MATERIALS AND METHODS: The study is carried out using the Zubal numerical phantom, and performing electromagnetic thermal co-simulations. The Pennes model is used for thermal balance; the dissipation models for the magnetic nanoparticles are those available in the literature. The results concerning the optimal therapeutic concentration of nanoparticles, obtained through the analysis, are validated using experimental data on the specific absorption rate of iron oxide nanoparticles, available in the literature. RESULTS: The numerical estimates obtained by applying the criterion to the treatment of brain tumours shows that the acceptable values for the product between the magnetic field amplitude and frequency may be two to four times larger than the safety threshold of 4.85 * 10(8)A/m/s usually considered. This would allow the reduction of the dosage of nanoparticles required for an effective treatment. In particular, depending on the tumour depth, concentrations of nanoparticles smaller than 10 mg/mL of tumour may be sufficient for heating tumours smaller than 10 mm above 42 degrees C. Moreover, the study of the clinical scalability shows that, whatever the tumour position, lesions larger than 15 mm may be successfully treated with concentrations lower than 10 mg/mL. The criterion also allows the prediction of the temperature rise in healthy tissue, thus assuring safe treatment. CONCLUSIONS: The criterion can represent a helpful tool for planning and optimising an effective hyperthermia treatment. PMID- 27268795 TI - The Ensembl Variant Effect Predictor. AB - The Ensembl Variant Effect Predictor is a powerful toolset for the analysis, annotation, and prioritization of genomic variants in coding and non-coding regions. It provides access to an extensive collection of genomic annotation, with a variety of interfaces to suit different requirements, and simple options for configuring and extending analysis. It is open source, free to use, and supports full reproducibility of results. The Ensembl Variant Effect Predictor can simplify and accelerate variant interpretation in a wide range of study designs. PMID- 27268851 TI - Movement rehabilitation: are the principles of re-learning in the recovery of function the same as those of original learning? AB - This paper addresses the change in movement dynamics in rehabilitation through discussing issues that pertain to the question as to whether the principles of re learning in functional recovery are the same as those of original learning. The many varieties of disease and injury states lead to significant differences in the constraints to action and these impairments in turn influence the pathway of change in re-learning and/or recovery of function. These altered constraints channel the effectiveness of many conditions and strategies of practice that influence learning and performance. Nevertheless, it is proposed that there is a small set of principles for the change in dynamics of motor learning, which drive the continuously evolving stability and instability of movement forms through the lifespan. However, this common set of dynamical principles is realized in individual pathways of change in the movement dynamics of learning, re-learning and recovery of function. The inherent individual differences of humans and environments insure that the coordination, control and skill of movement rehabilitation are challenged in distinct ways by the changing constraints arising from the many manifestations of disease and injury. Implications for rehabilitation The many varieties of disease and injury states lead to significant differences in the constraints to action that in turn influence the pathway of change in re-learning and/or recovery of function, and the effectiveness of the many conditions/strategies of practice to influence learning and performance. There are a small set of principles for the change in dynamics of motor learning that drive the continuously evolving ebb and flow of stability and instability of movement forms through the lifespan. The inherent individual differences of humans and environments insure that the coordination, control and skill of movement rehabilitation are uniquely challenged by the changing constraints arising from the many manifestations of disease and injury. PMID- 27268852 TI - Digit Span Performance in Children with Dystrophinopathy: A Verbal Span or Working Memory Contribution? AB - OBJECTIVES: In a large cohort of boys with dystrophinopathies and their unaffected siblings, we examined whether consistently observed performance on digit span is due primarily to a verbal span or executive deficit. We additionally assessed whether digit span performance contributed to the observed variability in reading performance noted in this population. METHODS: Performance of 170 boys with dystrophinopathy was compared to 95 unaffected sibling controls on measures of verbal function, reading, and digit span. Maximum digit span forward (DSF) and backward (DSB) lengths were converted to Z-scores using normative data. Independent sample t tests, analysis of variance, and hierarchical multiple regression were run (alpha=0.05). RESULTS: Probands performed worse than controls on digit span, even after accounting for differences in general verbal function (p<.0001). Differences were significant for both DSF (p<.005) and DSB (p<.0001) span length, and an interaction effect yielded significantly worse DSB compared with DSF (p=.01). Reading performance was also lower in probands (p<.0001). The contribution of general level of verbal function, and forward and backward span lengths, did not vary between groups. CONCLUSIONS: In boys with dystrophinopathy, decreased performance on digit span appears to be due to both decreased span forward (measuring verbal span only) and backward (measuring verbal span and working memory). The extent to which sibling controls exhibited better performance compared to the probands was significantly greater for backward span when compared with forward span. Thus, immediate verbal memory and executive control are differentially compromised among boys with dystrophinopathy, and both of these abilities independently contribute to reading performance. (JINS, 2016, 22, 777-784). PMID- 27268853 TI - Novel plasmid conferring kanamycin and tetracycline resistance in the turkey derived Campylobacter jejuni strain 11601MD. AB - In Campylobacter spp., resistance to the antimicrobials kanamycin and tetracycline is frequently associated with plasmid-borne genes. However, relatively few plasmids of Campylobacter jejuni have been fully characterized to date. A novel plasmid (p11601MD; 44,095nt) harboring tet(O) was identified in C. jejuni strain 11601MD, which was isolated from the jejunum of a turkey produced conventionally in North Carolina. Analysis of the p11601MD sequence revealed the presence of a high-GC content cassette with four genes that included tet(O) and a putative aminoglycoside transferase gene (aphA-3) highly similar to kanamycin resistance determinants. Several genes putatively involved in conjugative transfer were also identified on the plasmid. These findings will contribute to a better understanding of the distribution of potentially self-mobilizing plasmids harboring antibiotic resistance determinants in Campylobacter spp. from turkeys and other sources. PMID- 27268855 TI - Are maintenance and continuous therapies indicated for every patient with multiple myeloma? AB - Maintenance therapy after autologous stem cell transplantation, as well as continuous regimens for older, transplant ineligible patients, are emerging as an effective strategy to control the minimal residual disease that persists after response to initial treatments and is the main cause of relapse in patients affected by multiple myeloma (MM). However, though such approaches have consistently demonstrated in clinical trials to be able to delay disease recurrence, thus improving progression-free survival and, at least in some studies, overall survival, the use of these long term therapies (LTTs) in the daily clinical practice is not uniformly applied and some questions remains unanswered. This article aims to provide a synthetic discussion of the most consistent data on novel agent-based LTTs in newly diagnosed MM, to recognize the best candidate for these treatments and to describe a landscape of their possible future application. PMID- 27268854 TI - A review of the methods used to define glucocorticoid exposure and risk attribution when investigating the risk of fracture in a rheumatoid arthritis population. AB - BACKGROUND: Glucocorticoid therapy is used widely in patients with rheumatoid arthritis (RA) with good efficacy but concerns about safety including fractures. Estimates of fracture risk for any given patient are complicated by the dynamic pattern of glucocorticoid use, where patients vary in their dose, duration and timing of glucocorticoid use. OBJECTIVE: To investigate which methods are currently used to attribute fractures to glucocorticoid exposure and investigate whether such methods can consider individual treatment patterns. RESULTS: Thirty eight studies used five common definitions of risk attribution to glucocorticoid exposure: "current use", "ever use", "daily dose", "cumulative dose" and "time variant". One study attempted to combine multiple definitions where "cumulative dose" was nested within "daily dose", covering the effects of dose and duration but not timing. The majority of results demonstrated an equivocal or increased risk of fracture with increased exposure, although there was wide variation, with odds ratios, hazard ratios and relative risks ranging from 0.16 to 8.16. Within definitions there was also variability in the results with the smallest range for "time variant", 1.07 to 2.8, and the largest for "cumulative dose", ranging from risk estimates of 0.88 to 8.12. CONCLUSION: Many studies have looked into the effect of glucocorticoids on fracture risk in patients with RA. Despite this, there is no clear consensus about the magnitude of risk. This is a consequence of the varied analysis models and their different assumptions. Moreover, no current analysis method allows consideration of dose, duration and timing of glucocorticoid therapy, preventing a clear understanding of fracture risk for patients and their individual treatment patterns. PMID- 27268856 TI - New concepts in HIV-1 vaccine development. AB - With 2 million people newly infected with HIV-1 in 2014, an effective HIV-1 vaccine remains a major public health priority. HIV-1 vaccine efficacy trials in humans, complemented by active and passive immunization studies in non-human primates, have identified several key vaccine-induced immunological responses that may correlate with protection against HIV-1 infection. Potential correlates of protection in these studies include V2-specific, polyfunctional, and broadly neutralizing antibody responses, as well as effector memory T cell responses. Here we review how these correlates of protection are guiding current approaches to HIV-1 vaccine development. These approaches include improvements on the ALVAC HIV/AIDSVAX B/E vaccine regimen used in the RV144 clinical trial in Thailand, adenovirus serotype 26 vectors with gp140 boosting, intravenous infusions of bNAbs, and replicating viral vectors. PMID- 27268867 TI - Use of formative research and social network theory to develop a group walking intervention: Sumter County on the Move! AB - Although social support is a frequently cited enabler of physical activity, few studies have examined how to harness social support in interventions. This paper describes community-based formative research to design a walking program for mobilizing naturally occurring social networks to support increases in walking behavior. Focus group methods were used to engage community members in discussions about desired walking program features. The research was conducted with underserved communities in Sumter County, South Carolina. The majority of focus group participants were women (76%) and African American (92%). Several important themes emerged from the focus group results regarding attitudes toward walking, facilitators of and barriers to walking, ideal walking program characteristics, and strategies for encouraging community members to walk. Most noteably, the role of existing social networks as a supportive influence on physical activity was a recurring theme in our formative research and a gap in the existing evidence base. The resulting walking program focused on strategies for mobilizing, supporting and reinforcing existing social networks as mechanisms for increasing walking. Our approach to linking theory, empirical evidence and community-based formative research for the development of a walking intervention offers an example for practitioners developing intervention strategies for a wide range of behaviors. PMID- 27268868 TI - Ability to downregulate the level of cyclin-dependent kinase inhibitor p27Kip1 after DNA damage is retained in chronic lymphocytic leukemia cells with functional ATM/p53 signaling pathway. PMID- 27268869 TI - [Effectiveness of an intervention to improve the implementation of a surgical safety check-list in a tertiary hospital]. AB - OBJECTIVE: To determine the percentage of verification of a Surgical Safety Checklist and improvements made. DESIGN: Quasi-experimental study in 28 Clinical Management Units with surgical activity in the University Hospital Virgen del Rocio (HUVR) and University Hospital Virgen Macarena (HUVM). A situation analysis was made to estimate the completing of a Surgical Safety Checklist (SSC), after which a new system of completing the SSC was introduced as an element of improvement, which included a reusable vinyl board. Subsequently, the prevalence over two periods was calculated, to assess the effectiveness of the intervention. RESULTS: A total 1,964 SSC were reviewed in the HUVR-HUVM in June (baseline), and in December 2013 and June 2014. A percentage completion of 65.8%, 86.2%, and 88% was obtained in the HUVR, and 70.9%, 77.2%, and 75% in the HUVM, respectively. Of these SSC, 15.1% (baseline) were completed entirely in the HUVR, increasing to 36.6% (P<.001), and 89.8% (P<.001) in the last measurement. In the HUVM, 15.6% (baseline) were fully completed, increasing to 18.3% (P=.323), and 29.4% (P=.001) in the last measurement. CONCLUSION: The percentage of completion of SSC obtained is around 80%, and is similar to that reported in the literature. The re-design of the SSC procedure, including the use of a vinyl board, the designation of SSC coordinator role, and professional staff training, is effective for improve outcomes in terms of completing the SSC, and quality of the completion. PMID- 27268870 TI - [Development and evolution of a balanced scorecard in primary health care: Lessons learned]. AB - OBJECTIVES: To describe the design, implementation, and monitoring of eSOAP (Primary Health Care Balanced Scorecard) and its role in the deployment of strategic objectives and clinical management, as well as to show the lessons learned during six years of follow-up. METHOD: Descriptive study areas: methodology (conceptual framework, strategic matrix, strategic map, and processes map), technology and standardisation. RESULTS: As of December 2014, 9,046 (78%) professionals are registered in eSOAP. A total of 381 indicators were measured from 16 data sources, of which 36% were of results (EFQM model), 39.1% of clinical management, and 20% were included in the Program Centre Contract. The Balanced Scorecard has enabled to deploy all strategic lines of Primary Health Care, and has enabled the healthcare professionals to evaluate the evolution of results over time, and at patient level (e.g. 16% increase in control of diabetic patients). A total of 295,779 reports were generated and 13,080 professionals were evaluated by goals. CONCLUSIONS: There was an increased use of the eSOAP application by the professionals. The Balanced Scorecard was the key in deploying Primary Health Care strategies. It has helped clinical management and improved relevant indicators (health, patient experience, and costs), such as the management models that we used as references (EFQM Kaplan and Norton), and new emerging scenarios (Triple aim). PMID- 27268871 TI - The Role of Gay Identity Confusion and Outness in Sex-Seeking on Mobile Dating Apps Among Men Who Have Sex With Men: A Conditional Process Analysis. AB - Mobile dating apps are now a popular platform for men who have sex with men (MSM) to connect with others. Based on the uses and gratifications (U&G) theory, this study explores the relationship between sex-seeking and the number of casual sex partners met through MSM-based mobile dating apps (Grindr, Jack'd, and SCRUFF). The conditional process analysis (N = 401) shows that this relationship was significant and was mediated by the intensity of app use. That is, sex-seeking indirectly affected the number of casual sex partners through the intensity of app use. Furthermore, gay identity confusion and outness to the world moderated this indirect effect: it was stronger when the user was either more confused about his sexuality or was less out to the world. This research introduces an alternative way to incorporate psychographics variables into the U&G framework. PMID- 27268906 TI - Chemical probes of quorum sensing: from compound development to biological discovery. AB - Bacteria can utilize chemical signals to coordinate the expression of group beneficial behaviors in a method of cell-cell communication called quorum sensing (QS). The discovery that QS controls the production of virulence factors and biofilm formation in many common pathogens has driven an explosion of research aimed at both deepening our fundamental understanding of these regulatory networks and developing chemical agents that can attenuate QS signaling. The inherently chemical nature of QS makes studying these pathways with small molecule tools a complementary approach to traditional microbiology techniques. Indeed, chemical tools are beginning to yield new insights into QS regulation and provide novel strategies to inhibit QS. Here, we review the most recent advances in the development of chemical probes of QS systems in Gram-negative bacteria, with an emphasis on the opportunistic pathogen Pseudomonas aeruginosa We first describe reports of novel small molecule modulators of QS receptors and QS signal synthases. Next, in several case studies, we showcase how chemical tools have been deployed to reveal new knowledge of QS biology and outline lessons for how researchers might best target QS to combat bacterial virulence. To close, we detail the outstanding challenges in the field and suggest strategies to overcome these issues. PMID- 27268908 TI - Enantioselective Intermolecular [2 + 2] Photocycloaddition Reactions of 2(1H) Quinolones Induced by Visible Light Irradiation. AB - In the presence of a chiral thioxanthone catalyst (10 mol %) the title compounds underwent a clean intermolecular [2 + 2] photocycloaddition with electron deficient olefins at lambda = 419 nm. The reactions not only proceeded with excellent regio- and diastereoselectivity but also delivered the respective cyclobutane products with significant enantiomeric excess (up to 95% ee). Key to the success of the reactions is a two-point hydrogen bonding between quinolone and catalyst enabling efficient energy transfer and high enantioface differentiation. Preliminary work indicated that solar irradiation can be used for this process and that the substrate scope can be further expanded to isoquinolones. PMID- 27268909 TI - Microenvironmental Control of Adipocyte Fate and Function. AB - The properties of tissue-specific microenvironments vary widely in the human body and demonstrably influence the structure and function of many cell types. Adipocytes are no exception, responding to cues in specialized niches to perform vital metabolic and endocrine functions. The adipose microenvironment is remodeled during tissue expansion to maintain the structural and functional integrity of the tissue and disrupted remodeling in obesity contributes to the progression of metabolic syndrome, breast cancer, and other malignancies. The increasing incidence of these obesity-related diseases and the recent focus on improved in vitro models of human tissue biology underscore growing interest in the regulatory role of adipocyte microenvironments in health and disease. PMID- 27268907 TI - Neglected filoviruses. AB - Eight viruses are currently assigned to the family Filoviridae Marburg virus, Sudan virus and, in particular, Ebola virus have received the most attention both by researchers and the public from 1967 to 2013. During this period, natural human filovirus disease outbreaks occurred sporadically in Equatorial Africa and, despite high case-fatality rates, never included more than several dozen to a few hundred infections per outbreak. Research emphasis shifted almost exclusively to Ebola virus in 2014, when this virus was identified as the cause of an outbreak that has thus far involved more than 28 646 people and caused more than 11 323 deaths in Western Africa. Consequently, major efforts are currently underway to develop licensed medical countermeasures against Ebola virus infection. However, the ecology of and mechanisms behind Ebola virus emergence are as little understood as they are for all other filoviruses. Consequently, the possibility of the future occurrence of a large disease outbreak caused by other less characterized filoviruses (i.e. Bundibugyo virus, Lloviu virus, Ravn virus, Reston virus and Tai Forest virus) is impossible to rule out. Yet, for many of these viruses, not even rudimentary research tools are available, let alone medical countermeasures. This review summarizes the current knowledge on these less well-characterized filoviruses. PMID- 27268911 TI - Smoking, hormonal factors and molecular markers in female lung cancer. AB - There has been substantial argumentation about differences in lung cancer occurrence and characteristics between men and women. Lung cancer incidence suggests that gender-related factors may influence lung cancer risk. The carcinogenic effect of tobacco smoke and the use of hormone replacement therapy could result in susceptibility to lung cancer among women. Mutations in EGFR and HER-2/neu genes, and ROS1 gene fusions may also play a role in gender-based survival rate differences. This review summarizes the latest data of disease markers and its usefulness in female lung cancer. PMID- 27268912 TI - Protein synthesis inhibitors of natural origin for CML therapy: semisynthetic homoharringtonine (Omacetaxine mepesuccinate). AB - Omacetaxine mepesuccinate is a drug approved in 2014 by FDA for the use in CML therapy in patients resistant to at least two thymidine kinase inhibitors (TKIs). It possesses unique mechanism of anticancer activity that is principally different from mechanism of activity of TKIs. Omacetaxine mepesuccinate inhibits protein translation through prevention of the initial elongation step of protein synthesis and its use benefits CML patients possessing the BCR-ABL oncogene. Because of the superior activity of Omacetaxine in patients who became resistant to therapy with TKIs, FDA decided on the accelerated approval of this drug taking its consideration not only its activity as such but also a favorable benefit-to risk profile in patients included into clinical studies. PMID- 27268910 TI - Cellular Organization and Cytoskeletal Regulation of the Hippo Signaling Network. AB - The Hippo signaling network integrates diverse upstream signals to control cell fate decisions and regulate organ growth. Recent studies have provided new insights into the cellular organization of Hippo signaling, its relationship to cell-cell junctions, and how the cytoskeleton modulates Hippo signaling. Cell cell junctions serve as platforms for Hippo signaling by localizing scaffolding proteins that interact with core components of the pathway. Interactions of Hippo pathway components with cell-cell junctions and the cytoskeleton also suggest potential mechanisms for the regulation of the pathway by cell contact and cell polarity. As our understanding of the complexity of Hippo signaling increases, a future challenge will be to understand how the diverse inputs into the pathway are integrated and to define their respective contributions in vivo. PMID- 27268913 TI - Malignant melanoma: diagnosis, treatment and cancer stem cells. AB - Malignant melanoma represents a neoplasm stemming from melanocytes or the cells that develop from melanocytes. Melanocytes, pigment-producing cells, arise from the neural crest and migrate to their final destinations in the skin, uveal tract, meninges, and mucosa. Most melanocytes are found at the epidermal-dermal junction of the skin, and the vast majority of melanocytes arise from cutaneous sites. Cancerous growths develop when unrepaired DNA damage to skin cells (most often caused by ultraviolet radiation from sunshine or tanning beds) triggers mutations (genetic defects) that lead the skin cells to multiply rapidly and form malignant tumours. Malignant tumours consist of heterogeneous populations of tumour cells. Cancer stem cells (CSC) represent a population of cells within a tumour with highly tumorigenic and chemoresistant properties. These cells may be identified by the expression of CSC markers and also by functional assays as tumour-initiating properties in vivo, high aldehyde dehydrogenase activity tested by Aldefluor assay. There are several key stem cells markers specified for malignant melanoma: CD20, CD133, ABCB5, CD271 and ALDH1A. The review provides a detailed overview of risk factors, diagnosis, treatment possibilities and specific properties of cancer stem cells in malignant melanoma. PMID- 27268914 TI - DNA from microdissected tissues may be extracted and stored on microscopic slides. AB - With regard to complex structure of tissues, laser capture microdissection represents an important step in analytical workflow streaming to proper molecular characterization of different cell types in examined samples. Therefore the simple method for simultaneous processing of higher numbers of microdissected tissues leading not only to rapid and efficient DNA isolation but allowing also the repeated sampling and easy storage may be useful in the practice of histopathological laboratories. We elaborated such a methodology applicable downstream after the microdissection from formalin-fixed paraffin embedded tissues.The tissues for examination are microdissected directly into the circular areas having the diameter 2 mm and marked on the microscopic slide. In this way, one slide is able to accommodate multiple samples. The DNA extraction is performed in low volume of buffer with Proteinase K in a droplet covered by mineral oil just on the slide. Mineral oil in the quality for molecular biology not only avoids evaporation during DNA extraction, but it helps to position the microdisssected tissue, to control the level of cell lysis microscopically and to protect the DNA sample during subsequent manipulations. We provided the evidence that DNA isolated by our methodology remains in the positions on microscopic slide for months without any changes in the lengths of available fragments and that it may be removed from each position repetitively for different kinds of analysis. The new methodological approach presented by us can be practically applied in broad spectrum of laboratories performing routinely genetic analysis on microdissected tissues. PMID- 27268915 TI - Daidzein exerts anti-tumor activity against bladder cancer cells via inhibition of FGFR3 pathway. AB - Bladder cancer is one of the causes of cancer-related death and has a high mortality rate. Daidzein, a natural isoflavone compound predominantly extracted from soybeans, has been reported to exhibit several bioactivities, including anti tumor. However, the effects of daidzein on bladder cancer remains unrevealed. Here we investigated the effects and molecular mechanisms of daidzein on bladder cancer using multiple in vitro cell lines and in vivo xenograft mice studies. Our results showed that daidzein reduced cell viability in a time- and concentration dependent manner. Daidzein significantly impaired colony formation, caused G1/S cell cycle arrest and induced apoptosis of the bladder cancer cells. We also verified that daidzein efficiently suppressed RT112 cell xenograft tumor growth in nude mice. Mechanism studies indicated that significant down-regulation of the FGFR3 signaling pathway was responsible for the efficacy of daidzein. The phosphorylation levels of FGFR3, Akt and Erk proteins were suppressed in association with the decreasing of some apoptosis-suppressing molecules under the daidzein treatment. Knockdown of endogenous FGFR3 impaired the activity of daidzein against bladder cancer, which suggested that the effect of daidzein was mainly mediated by FGFR3 pathway. In addition, the function model of daidzein was similar with FGFR3 antagonist PD173074 in RT112 cells. Taken together, the results this study demonstrate that daidzein is capable of inhibiting bladder cancer growth and might be a novel effective chemotherapeutic agent for the application to combat bladder carcinoma. PMID- 27268916 TI - Resveratrol inhibits hypoxia-induced glioma cell migration and invasion by the p STAT3/miR-34a axis. AB - Hypoxia promotes aggressiveness, angiogenesis and resistance in glioma. It has been reported that resveratrol has strong anti-tumor ability and can inhibit migration and invasion of varieties of tumor including glioma. However, whether resveratrol inhibits hypoxia-induced migration and invasion of glioma cells is still unknown. In this study, we found glioma U87 and U251 cells migration and invasion was reduced by resveratrol under hypoxia condition and higher doses led to stronger block, while proliferation of U87 and U251 cells was hardly effected. Mechanically, hypoxia-induced upregulation of phosphorylated signal transducer and activator of transcription 3(p-STAT3) was blocked by resveratrol. MicroRNA 34a (miR-34a) is a tumor suppressor whose promoter region has a conserved STAT3 binding site and can be negatively regulated by STAT3. Interestingly, miR-34a was downregulated under hypoxia but upregulated by resveratrol which was perhaps relevant to changes in level of p-STAT3. The effect of resveratrol on p-STAT3 and miR-34a was both time-and dose-dependent. Summarizing, resveratrol inhibits hypoxia-induced migration and invasion possibly via p-STAT3/miR-34a axis and this effect is both time-and dose-dependent. PMID- 27268917 TI - Knockdown of 14-kDa phosphohistidine phosphatase expression suppresses lung cancer cell growth in vivo possibly through inhibition of NF-kappaB signaling pathway. AB - In previous study, we reported that 14-kDa phosphohistidine phosphatase (PHP14) was associated with lung cancer cell migration and invasion. We also found that the expression of PHP14 was markedly increased in a part of human lung cancer tissues. In this study, we investigated the impact of PHP14 knockdown on lung cancer cell tumorigenesis in vitro and in vivo, as well as the regulatory pathway. Depletion of endogenous PHP14 expression in lung cancer cells reduced colony formation activity of lung cancer cells in vitro and inhibited the xenograft tumor growth in vivo. Further experiments revealed that the NF-kappaB signal pathway inhibitor PDTC inhibited the upregulated expression of MMP9 induced by PHP14 overexpression in lung cancer cells. Furthermore, knockdown of PHP14 in lung cancer cells correlated with decreased expression of a subset of NF kappaB-regulated genes, such as BCL-2, COX-2, MCP-1, MMP9 and VEGF-C, which play an important role in tumor progression. Together these data suggest that knockdown of PHP14 in lung cancer cells inhibits lung cancer tumor growth in vivo, possibly via regulating the NF-kappaB pathway. PMID- 27268919 TI - Genes and pathways identified in thyroid carcinoma based on bioinformatics analysis. AB - The objective of this study was to investigate the key genes and pathways associated with thyroid carcinoma. Based on the microarray data of GSE27155, we identified the differentially expressed genes (DEGs) between four types of thyroid carcinoma samples (papillary carcinoma (PTC), oncocytic carcinoma (OTC), follicular carcinoma (FTC) and anaplastic carcinoma (ATC)) and normal controls. With the obtained DEGs, we performed gene functional interaction (FI) network analysis. Then we conducted Venn diagram analysis to identify the intersection and specific DEGs of the four types of thyroid carcinomas. The intersections DEGs were performed by functional enrichment and transcription factor (TF) prediction analyses. These specific DEGs were performed by pathway enrichment analysis. There were respectively 323, 318, 118 and 1005 DEGs identified in PTC, OTC, FTC and ATC. Twelve sub-network modules were extracted based on gene FI network analysis and eight thyroid carcinoma-associated DEGs were involved in the network, such as TIMP1. Based on the Venn diagram analysis, 27 common DEGs were identified, such as HMGB3 which was regulated by TF of NKX3-1. There were 149 PTC specific DEGs (like CLDN1), 160 OTC-specific DEGs, 94 FTC-specific DEGs (like PPARG), and 789 ATC-specific DEGs (like CDK1). They were enriched in some pathways, such as Cell cycle, Citrate cycle, and Oxidative phosphorylation. TIMP1, HMGB3, CLDN1, CDK1 and PPARG as well as pathways of Cell cycle, Citrate cycle, and Oxidative phosphorylation may play important roles in the progression of thyroid carcinoma. PMID- 27268918 TI - Significant prognostic values of nuclear genes encoding mitochondrial complex I subunits in tumor patients. AB - In cancer biology, it remains still open question concerning the oncogenic versus oncosuppressor behavior of metabolic genes, which includes those encoding mitochondrial complex I (CI) subunits. The prognostic value of nuclear genome mRNAs expression of CI subunits is to be evaluated in the tumor patients. We used the Kaplan Meier plotter database, the cBio Cancer Genomics Portal, and the Oncomine in which gene expression data and survival information were from thousands of tumor patients to assess the relevance of nuclear genome mRNAs level of CI subunits to patients' survival, as well as their alterations in gene and expression level in tumors. We presented that the relative expression level of overwhelming majority of the nuclear genes of CI subunits with survival significance (overall survival, relapse free survival, progression free survival, distant metastasis free survival, post progression survival, and first progression), had consistent effects for patients in each type of four tumors separately, including breast cancer, ovarian cancer, lung cancer, and gastric cancer. However, in gene level, frequent cumulative or individual alteration of these genes could not significantly affect patients' survival and the overexpression of the individual gene was not ubiquitous in tumors versus normal tissues. Given that reprogrammed energy metabolism was viewed as an emerging hallmark of tumor, thus tumor patients' survival might potentially to be evaluated by certain threshold for overall expression of CI subunits. Comprehensive understanding of the nuclear genome encoded CI subunits may have guiding significance for the diagnosis and prognosis in tumor patients. PMID- 27268920 TI - Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy. AB - Presented study aimed to prepare A10 aptamer-modified poly (D,L-lactic-co glycolic acid) (PLGA) nanoparticles loaded with triplex forming oligonucleotides(TFO) for targeted prostate cancer therapy. We first synthesized a PLGA-PEG-Apt copolymer. The PLGA-PEG-Apt nanoparticles (NP-Apt) were loaded with TFO using double emulsion solvent evaporation method. Carboxy-fluorescein labeled TFO-NP-Apt, TFO-NP and TFO were prepared for cellular uptake experiments. Cell counting kit-8 (CCK-8) test was used to determine the ability of TFO-NP-Apt to inhibit LNCaP cell proliferation. RT-PCR and Western blot was conducted to analyze AR gene expressing. Then, a mouse model of prostate cancer was used to evaluate the anti-cancer effect of TFO-NP-Apt in vivo. We confirmed that the PLGA PEG-Apt conjugation was successful. The TFO encapsulation efficiency and drug loading percentage were 46.1+/- 3.6% and 40.8+/-5.3%, respectively. TFO-NP-Apt showed a more efficient cellular uptake than TFO-NP or TFO in LNCaP cells. TFO-NP Apt was significantly more cytotoxic than TFO-NP and TFO in the CCK-8 test (p<0.001). TFO-NP-Apt silenced the AR gene better than unconjugated Apt, naked TFO, NP or saline. TFO-NP-Apt were more effective than TFO-NP, naked TFO, NP and saline at inhibiting prostate cancer growth in vivo (p<0.05). Aptamer-modified TFO-loaded PLGA nanoparticles may prove useful in targeted therapy for advanced prostate cancer. PMID- 27268921 TI - Prognostic significance of miR-23b in combination with P-gp, MRP and LRP/MVP expression in non-small cell lung cancer. AB - Recently, miR-23b has emerged as a promising new cancer biomarker but its role in lung cancer has not been established yet. Patients still do not respond well to available treatments, probably due to expression of multidrug resistance (MDR) proteins, such as P-gp, MRP and LRP/MVP. The aim of this study was to determine the role of miR-23b in non-small cell lung cancer (NSCLC) and its relationship to the patient outcome together with MDR transporter proteins. We immunohistochemically evaluated expression of P-gp, MRP and LRP/MVP and quantified the relative levels of miR-23b in 62 NSCLC patients' samples. The prognostic significance of miR-23b and MDR proteins was tested by Kaplan-Meier and Cox-regression analysis. Our results showed that miR-23b is mostly downregulated in NSCLC samples (57/62) and that its upregulation in tumors is connected with longer progression-free survival (PFS; P = 0.065) and overall survival (OS; P = 0.048). The Cox proportional hazard model revealed that the risk of death or relapse in NSCLC patients with miR-23b downregulation increases together with LRP/MVP expression and both risks decrease with miR-23b upregulation (HRPFS = 4.342, PPFS = 0.022; HROS = 4.408, POS = 0.015). Our findings indicate that miR-23b, especially in combination with LRP/MVP expression, might serve as a suitable prognostic biomarker for NSCLC patients. PMID- 27268922 TI - Expression of ER stress markers (GRP78/BiP and PERK) in patients with tongue cancer. AB - The glucose-regulated protein (GRP78/BiP) and PKR-like endoplasmic reticulum kinase (PERK) plays a crucial role in the endoplasmic reticulum (ER) stress response. GRP78/BiP is highly elevated in various human cancers. Our study is to examine the clinicopathological significance of GRP78/BiP and PERK expression in patients with tongue cancer. A total of 85 tongue cancer patients were analyzed, and tumor specimens were stained by immunohistochemistry for GRP78/BiP, PERK, GLUT1, Ki-67 and microvessel density (MVD) determined by CD34.GRP78/BiP and PERK were highly expressed in 47% and 35% of all patients, respectively. GRP78/BiP disclosed a significant relationship with PERK expression, lymphatic permeation, vascular invasion, glucose metabolism and cell proliferation. The expression of GRP78/BiP was significantly higher in metastatic sites than in primary sites (79% vs. 47%, p=0.003). We found that the high expression of GRP78/BiP was proven to be an independent prognostic factor for predicting poor outcome in patients with tongue cancer. In the analysis of PFS, PERK was identified as an independent predictor. The increased GRP78/BiP expression was clarified as an independent prognostic marker for predicting worse outcome. Our study suggests that the expression of GRP78/BiP as ER stress marker is important in the pathogenesis and development of tongue cancer. PMID- 27268923 TI - Prognostic factors to predict outcome of reduced intensity allogeneic haematopoietic cell transplantation for chronic lymphocytic leukemia. AB - Despite advances in immunochemotherapy CLL remains an incurable disease.. Allogeneic haematopoietic cell transplantation (HCT) has proven curative potential with ability to overcome adverse prognostic factors, however due to its toxicity it is generally perceived as the last option. We performed retrospective study to explore the outcomes and possible determinants of survival in the unselected consecutive cohort of 68 CLL patients (median age 59 years) receiving reduced intensity HCT as a part of salvage therapy in 2 Czech centers. The median interval from diagnosis to HCT was 69 months with median 3 of prior regimens, all patients were refractory to purine analogues. 49% of patients were transplanted with advanced (i.e. refractory or progressive disease or CR/PR>3), 38% had high risk cytogenetics. With median follow-up of 35 months the 3-year Kaplan-Meier survival probability for OS and PFS were 39% and 26%, respectively. Altogether 18 patients (26%) have relapsed or progressed. During the follow-up 41 patients died, 32 (78%) of transplant related factors (NRM), the others of relapse or disease progression.Univariate analysis failed to identify any clinical and pre- or post-transplant variables having clear prognostic significance for OS or PFS. The marginal OS advantage favoring HCT performed recently was detected (3-year OS: 31% for HCT until 2006 and 47% thereafter, p=0.0923). In multivariable hazards model only the female donors were associated with shorter OS (HR 2.278, p=0.016) whereas transplanted T-cell> 2.75x108/kg predicted inferior PFS(HR 1.957, p=0.035). No prognostic impact of donor type, age of donor and recipient, HLA mismatch, disease status pre-HCT, number of previous therapy lines, interval from dg. to HCT and number of transplanted hematopoietic cells was found. Our findings support the conclusion that alloHCT is able to overcome well known negative cytogenetic prognostic factors and that preferring male to female donors could be beneficial. PMID- 27268924 TI - Cardiac tamponade - unusual clinical manifestation of undiagnosed malignant neoplasm. AB - Cardiac tamponade may be the first or predominant symptom of some pathologies but its etiology is not uncommonly unknown on admission to hospital. The purpose of this study was to evaluate the predominant causes of cardiac tamponade in previously healthy patients treated emergently in a single cardiac surgical center. The study involved 81 patients with the mean age of 58.1+/-16.0 years who underwent emergent subxyphoid pericardiotomy due to cardiac tamponade. Pericardial effusion was analyzed macro- and microscopically. Examinations done in the cardiac surgical department revealed pericarditis secondary to infection (n=17) or autoimmunologic processes (n=2) and malignancy in 18 patients (predominantly of the lungs (n=11)). Pericardial effusion obtained from patients with viral and autoimmunologic-induced pericarditis was straw-color and odorless while with bacterial infections dark yellow, iridescent and usually malodorous. Additional workup in the regional hospitals enabled to reveal malignant tumors in 29 patients, leukemia or lymphoma in 5 subjects. In all but one of the neoplastic cases, pericardial fluid was turbid and dark red or plummy. In 10 patients etiology of tamponade remained unknown. In conclusion, cardiac tamponade in previously healthy patients may be occasionally the predominant symptom of cancer, especially of the lungs. Macroscopic intraoperative appearance of pericardial fluid may be helpful in identification of causative condition of cardiac tamponade. PMID- 27268925 TI - Efficacy of intra-arterial neoadjuvant chemotherapy through the superior epigastric artery in the treatment of locally advanced triple negative breast cancer. AB - Triple negative breast cancer (TNBC) is associated with aggressive behaviour and poor prognosis, but has limited treatment options. To explore novel and effective therapies against TNBC, we retrospectively analyzed the efficacy of neoadjuvant intra-arterial chemotherapy through the superior epigastric artery in the treatment of locally advanced TNBC. Fifty-one locally advanced TNBC patients who received this neoadjuvant therapy from Mar 2001 to Mar 2012 were included in this study. The superior epigastric artery was selected for cannulation to deliver chemotherapy drugs. The regimen for intra-arterial chemoinfusion consisted of 75 mg/m2 epirubicin and 75 mg/m2 docetaxel. Clinical and pathological tumor responses, disease free survival (DFS), overall survival (OS), and toxicity profiles were recorded and retrospectively analyzed. In 51 patients treated with neoadjuvant intra-arterial chemoinfusion through the superior epigastric artery, the overall response rate (ORR) was 84.3%; 16 patients achieved pathological complete response (pCR). Following surgical treatment and adjuvant chemotherapy, 5-year DFS and OS were 72.4% and 75.9%, respectively, in the study population. In addition, this neoadjuvant approach showed favorable toxicity profiles. Moreover, patients who achieved pCR showed a superior survival outcome compared with those who did not. Cox regression analysis indicated that Ki-67 expression is an independent predictor for DFS and OS. Our results suggest that intra-arterial chemotherapy through the superior epigastric artery has great therapeutic potential for the treatment of locally advanced TNBC. This approach merits further clinical evaluation and may become a novel therapeutic option for locally advanced TNBC. PMID- 27268926 TI - Electroneurography in the evaluation of oxaliplatin-induced neuropathy in colorectal cancer patients. AB - Cold-induced neuropathy is the most observed side effect of oxaliplatin. Presence of neuropathy is routinely assessed by electroneurographical examination. The use of electroneurography has not been a part of typical oncological monitoring and treatment protocols, leading to untreated, irreversible damage to patients' peripheral nerves, undiagnosed for long periods of time. 36 colorectal cancer patients followed FOLFOX4 with/without bevacizumab or XELOX were enrolled between February 2013 and January 2015 in the study at the University Hospital Oncological Department, Krakow, Poland. Electroneurography was performed prior to the first cycle of chemotherapy and after the 4th cycle. 32 out of 36 enrolled patients completed neurological evaluation. Pre-treatment neurographic examination revealed presence of peripheral neuropathy in 10 (31.25%) patients; 6 (18.75%) had sensory neuropathy and 4 (12.5%) had mixed, sensorimotor neuropathy. After treatment examination revealed significant increase in the number of neuropathic patients; presence of peripheral neuropathy was observed in 19 patients (59%), sensory polyneuropathy was diagnosed in10 patients (31.25%) and mixed neuropathy was diagnosed in 9 patients (28.13%). Early electrophysiological monitoring followed by a symptom dependent oxaliplatin regimen would be highly beneficial for patients undergoing oxaliplatin treatment, improving their well being and positively affecting their life quality. PMID- 27268927 TI - Analysis of circulating miRNAs 21 and 375 as potential biomarkers for early diagnosis of prostate cancer. AB - To investigate the diagnostic potential of plasma miR-21 and miR-375 by comparing their levels in prostate cancer (PCa) patients to subjects without cancer in a Chinese population. The study population included 57 PCa patients and 28 benign prostatic hyperplasia (BPH) patients. The plasma levels of miR-21 and miR-375 were quantitated with Taqman based quantitative real-time polymerase chain reaction. In the BPH group, the median relative expression levels of miR-21 and miR-375 were 0.07 and 0.55, respectively; In the PCa group, the median values of miR-21 and miR-375 were 1.32 and 1.74, respectively. Both miR-21 (p=0.014) and miR-375 (p=0.005) plasma levels were significantly higher in PCa group than in BPH group. Using ROC analysis the AUC of miR-21 was 0.799, 95% CI between 0.690 and 0.908 (p=8*10-6); for miR-375, the AUC was 0.757, 95% CI between 0.640-0.874 (p=0.000126). The largest AUC (0.881) was obtained when the data of miR-21, miR 375 and PSA were combined, with a sensitivity of 87.7% and a specificity of 75%. The results of this study showed that circulating miR-21 and miR-375 can discriminate PCa patients from BPH controls at early stages. Combinations of the studied miRNAs and PSA remarkably increased specificity compared with PSA alone. The combination method has the potential to be used as a noninvasive diagnostic cocktail for PCa screening. PMID- 27268928 TI - Genetic variants and risk of prostate cancer using pathway analysis of a genome wide association study. AB - This study explored candidate causal single nucleotide polymorphisms (SNPs) to clarify the biological mechanism of prostate cancer (PCa). Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied using a PCa genome wide association study (GWAS) dataset that included 473,736 SNPs in 1151 cases of PCa and 1156 controls of European ancestry. Five candidate causal SNPs, three candidate causal genes, and two candidate causal pathways were identified using integrating linkage disequilibrium analysis, functional SNP annotation, and pathway-based analysis. The ICSNPathway analysis suggested three hypothetical mechanisms of PCa. The first was rs13112390, rs13112358, rs2048074 to nei-like DNA glycosylase 3 (NEIL3) gene to damaged DNA binding. The second was rs3087386 to REV1, DNA directed polymerase (REV1) gene to damaged DNA binding. The third was rs1063134 to potassium channel, inwardly rectifying subfamily J, member 4 (KCNJ4) gene to inward rectifier potassium channel activity. PMID- 27268929 TI - Indication of pre-surgical radiochemotherapy enhances psychosocial morbidity among patients with resectable locally advanced rectal cancer. AB - Patients with cancer experience stress-determined psychosocial comorbidities and behavioural alterations. Patients expectation to be cured by the first line surgery and their emotional status can be negatively influenced by the decision to include neoadjuvant long-course radiotherapy prior to surgical intervention. From the patient's perspective such treatment algorithmindicates incurability of the disease. The aim of this study was to analyse the extent and dynamics of stress and related psychosocial disturbances among patients with resectable rectal cancer to whom the neoadjuvant radiochemotherapy before surgery has been indicated.Three standardised assessment tools evaluating psychosocial morbidity of rectal cancer patients have been implemented: The EORTC QLQ C30-3, the EORTC QLQ CR29 module and the HADS questionnaires previously tested for internal consistency were answered by patients before and after long-course radiotherapy and after surgery and the scores of clinical and psychosocial values were evaluated by means of the EORTC and HADS manuals. The most profound psychosocial distress was experienced by patients after the decision to apply neoadjuvant radiotherapy and concomitant chemotherapy before surgical intervention. The involvement of pre-surgical radiotherapy into the treatment algorithm increased emotional disturbances (anxiety, feelings of hopelessness) and negatively influenced patient's treatment adherence and positive expectations from the healing process. The negative psychosocial consequences appeared to be more enhanced in female patients. Despite provided information about advances of neoadjuvant radiotherapy onto success of surgical intervention, the emotional and cognitive disorders improved only slightly. The results clearly indicate that addressed communication and targeted psychosocial support has to find place before pre-surgical radiochemotherapy and as a standard part through the trajectory of the entire multimodal rectal cancer treatment. PMID- 27268930 TI - Stage of bladder cancer in Central Europe - Polish perspective. AB - Mortality rate from bladder cancer in Europe is the highest in its Central Region. This study is an attempt to find underlying factors by proper characterisation of large cohort of Polish patients with bladder cancer.This is a multicentre study enrolling 1360 consecutive patients diagnosed with primary urothelial carcinoma of the bladder in years 2012-2013 in Poland. All patients underwent transurethral resection of the bladder tumor. Data on staging and grading of all cancers were collected, as well as several demographic and clinical factors were tested for the association with muscle invasiveness of the cancer.Mean age of the cohort was 69.6 years, male to female ratio was 3:1. Bladder cancer stage Ta, T1 and muscle-invasive (MIBC) was diagnosed in 533 (39.2%), 516 (37.9%) and 296 (21.8%) patients, respectively. Patients with MIBC were older (73 vs. 68 years, p<0.05), had lower body mass index (25.4 vs. 26.5 kg/m2, p<0.05), lower haemoglobin concentration (12.2 vs. 13.4 mg/l, p<0.05), longer history of haematuria (86.2 vs. 74.4 days) and longer time interval from first symptom to diagnosis (118.0 vs. 88.2 days), compared to patients with Ta and T1 tumors.High mortality rate from bladder cancer in Central Europe can result from very high incidence of high-risk T1 tumors and high prevalence of prognostic factors of poor survival. PMID- 27268931 TI - Salmonella enterica isolates from layer farm environments are able to form biofilm on eggshell surfaces. AB - This study examined the eggshell biofilm forming ability of Salmonella enterica isolates recovered from egg farms. Multicellular behaviour and biofilm production were examined at 22 and 37 degrees C by Congo red morphology and the crystal violet staining assay. The results indicated that the biofilm forming behaviour of Salmonella isolates was dependent on temperature and associated with serovars. Significantly greater biofilm production was observed at 22 degrees C compared with 37 degrees C. The number of viable biofilm cells attached to eggshells after incubation for 48 h at 22 degrees C was significantly influenced by serovar. Scanning electron microscopic examination revealed firm attachment of bacterial cells to the eggshell surface. The relative expression of csgD and adrA gene was significantly higher in eggshell biofilm cells of S. Mbandaka and S. Oranienburg. These findings demonstrate that Salmonella isolates are capable of forming biofilm on the eggshell surface and that this behaviour is influenced by temperature and serovar. PMID- 27268932 TI - Centennial Celebration: Endocrine Reviews Past Highlights for June. PMID- 27268935 TI - Modelling the impact of liner shipping network perturbations on container cargo routing: Southeast Asia to Europe application. AB - Understanding how container routing stands to be impacted by different scenarios of liner shipping network perturbations such as natural disasters or new major infrastructure developments is of key importance for decision-making in the liner shipping industry. The variety of actors and processes within modern supply chains and the complexity of their relationships have previously led to the development of simulation-based models, whose application has been largely compromised by their dependency on extensive and often confidential sets of data. This study proposes the application of optimisation techniques less dependent on complex data sets in order to develop a quantitative framework to assess the impacts of disruptive events on liner shipping networks. We provide a categorization of liner network perturbations, differentiating between systemic and external and formulate a container assignment model that minimises routing costs extending previous implementations to allow feasible solutions when routing capacity is reduced below transport demand. We develop a base case network for the Southeast Asia to Europe liner shipping trade and review of accidents related to port disruptions for two scenarios of seismic and political conflict hazards. Numerical results identify alternative routing paths and costs in the aftermath of port disruptions scenarios and suggest higher vulnerability of intra-regional connectivity. PMID- 27268936 TI - [Cost effectiveness and budget impact analysis of inhaled nitric oxide in a neonatal unit from the perspective of the public health system]. AB - : Inhaled nitric oxide (iNO) is currently the first-line therapy in severe hypoxaemic respiratory failure of the newborn. Most of regional neonatal centres in Chile do not have this therapeutic alternative. OBJECTIVE: To determine the cost effectiveness of inhaled nitric oxide in the treatment of respiratory failure associated with pulmonary hypertension of the newborn compared to the usual care, including the transfer to a more complex unit. PATIENTS AND METHOD: A clinical decision tree was designed from the perspective of Chilean Public Health Service. Incremental cost effectiveness rates (ICER) were calculated, deterministic sensitivity analysis was performed, and probabilistic budget impact was estimated using: TreeAge Pro Healthcare 2014 software. RESULTS: The iNO option leads to an increase in mean cost of $ 11.7 million Chilean pesos (?15,000) per patient treated, with an ICER compared with the usual care of $23 million pesos (?30,000) in case of death or ECMO avoided. By sensitising the results by incidence, it was found that from 7 cases and upwards treated annually, inhaled nitric oxide is less costly than the transfer to a more complex unit. CONCLUSIONS: From the perspective of a Chilean regional hospital, incorporating inhaled nitric oxide into the management of neonatal respiratory failure is the optimal alternative in most scenarios. PMID- 27268937 TI - Rh-Catalyzed N-O Bond Cleavage of Anthranil: A C-H Amination Reagent for Simultaneous Incorporation of Amine and a Functional Group. AB - A novel Rh(III)-catalyzed C-H bond amination with the simultaneous release of a formyl group at distal positions is realized employing anthranil as a new type of C-H amination reagent. This chemistry provides an efficient protocol for the synthesis of 2-acyl diarylamines, which are important structural motifs in many bioactive compounds. This new type of C-H amination reagent possesses the advantages of high atom economy, avoids the use of external oxidants, and enables further transformation of the amination products. PMID- 27268938 TI - Honey Bees' Behavior Is Impaired by Chronic Exposure to the Neonicotinoid Thiacloprid in the Field. AB - The decline of pollinators worldwide is of growing concern and has been related to the use of plant-protecting chemicals. Most studies have focused on three neonicotinoid insecticides (clothianidin, imidacloprid, and thiamethoxam) currently subject to a moratorium in the EU. Here, we focus on thiacloprid, a widely used cyano-substituted neonicotinoid thought to be less toxic to honey bees and of which use has increased in the last years. Honey bees (Apis mellifera carnica) were exposed chronically to thiacloprid in the field for several weeks at a sublethal concentration. Foraging behavior, homing success, navigation performance, and social communication were impaired, and thiacloprid residue levels increased both in the foragers and the nest mates over time. The effects observed in the field were not due to a repellent taste of the substance. For the first time, we present the necessary data for the risk evaluation of thiacloprid taken up chronically by honey bees in field conditions. PMID- 27268939 TI - Tocilizumab in recent polymyalgia rheumatica: how can we manage the interleukin-6 blockage? PMID- 27268940 TI - A Snapshot of Coagulopathy After Cardiopulmonary Bypass. AB - Cardiac surgery involving cardiopulmonary bypass (CPB) is often associated with important blood loss, allogeneic blood product usage, morbidity, and mortality. Coagulopathy during CPB is complex, and the current lack of uniformity for triggers and hemostatic agents has led to a wide variability in bleeding treatment. The aim of this review is to provide a simplified picture of the data available on patients' coagulation status at the end of CPB in order to provide relevant information for the development of tailored transfusion algorithms. A nonsystematic literature review was carried out to identify changes in coagulation parameters during CPB. Both prothrombin time and activated partial thromboplastin time increased during CPB, by a median of 33.3% and 17.9%, respectively. However, there was marked variability across the published studies, indicating these tests may be unreliable for guiding hemostatic therapy. Some thrombin generation (TG) parameters were affected, as indicated by a median increase in TG lag time of 55.0%, a decrease in TG peak of 17.5%, and only a slight decrease in endogenous thrombin potential of 7%. The most affected parameters were fibrinogen levels and platelet count/function. Both plasma fibrinogen concentration and FIBTEM maximum clot firmness decreased during CPB (median change of 36.4% and 33.3%, respectively) as did platelet count (44.5%) and platelet component (34.2%). This review provides initial information regarding changes in coagulation parameters during CPB but highlights the variability in the reported results. Further studies are warranted to guide physicians on the parameters most appropriate to guide hemostatic therapy. PMID- 27268941 TI - An Algorithmic Approach to Management of Venous Thromboembolism. AB - Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Factors such as the presence of transient risk factors for VTE, risk of bleeding, and location of deep vein thrombosis (DVT) determine the duration of anticoagulation. Extended anticoagulation is offered to patients with unprovoked pulmonary embolism (PE) or proximal DVT and a low risk of bleeding. Anticoagulation for 3 months is advised in patients with provoked DVT or PE, high risk of bleeding, and isolated distal or upper extremity DVT. In patients with unprovoked PE or proximal DVT and a low risk of bleeding, who want to stop anticoagulation after 3 months, further risk stratification is necessary. Clinical scoring system, and thrombophilia testing otherwise not routinely performed, may be considered to measure risk of annual recurrence in such cases. Short-term anticoagulation may be considered in subsegmental PE and superficial vein thrombosis, particularly if patients are at low risk of bleeding and have persistent risk factors for recurrent VTE. In cases of catheter-associated thrombosis, the catheter need not be removed routinely, and the patient may be anticoagulated for 3 months or longer if the catheter is maintained in patients with cancer. Extensive screening for occult cancer in cases of unprovoked VTE is not beneficial. New oral anticoagulants such as apixaban, rivaroxaban, or dabigatran may be preferred to vitamin K antagonists in patients without cancer or renal failure, more so after the development of reversal agents such as idarucizumab and andexanet alfa. PMID- 27268942 TI - Improved Synthesis of Larger Resorcinarenes. AB - The synthesis of the larger resorcin[5 and 6]arene macrocycles [5](OMe) and [6](OMe) has been realized by a Lewis acid-catalyzed condensation of 1,3 dimethoxy-2-methylbenzene with paraformaldehyde in o-dichlorobenzene as the solvent. The methoxy-resorcin[5 and 6]arenes were quantitatively demethylated by treatment with BBr3 to obtain the corresponding macrocycles with free OH groups. X-ray studies showed that in the solid state both the conformation and the packing of [6](OMe) and [5](OMe) are driven by C-H...O, C-H...pi, and pi...pi interactions. PMID- 27268943 TI - Unloading results in rapid loss of TGFbeta signaling in articular cartilage: role of loading-induced TGFbeta signaling in maintenance of articular chondrocyte phenotype? AB - OBJECTIVE: Recently it was shown that loading of articular cartilage explants activates TGFbeta signaling. Here we investigated if in vivo chondrocytes express permanently high TGFbeta signaling, and the consequence of the loss of compressive loading-mediated TGFbeta signaling on chondrocyte function and phenotype. METHOD: Bovine articular cartilage explants were collected within 10 min post mortem and stained immediately and after 30, 60 and 360 min for phosphorylated-Smad2, indicating active TGFbeta signaling. Explants were unloaded for 48 h and subsequently repeatedly loaded with a compressive load of 3 MPa. In addition, explants were cultured unloaded for 2 weeks and the effect of loading or exogenous TGFbeta on proteoglycan level and chondrocyte phenotype (Col10a1 mRNA expression) was analyzed. RESULTS: Unloading of articular cartilage results in rapid loss of TGFbeta signaling while subsequent compressive loading swiftly restored this. Loading and exogenous TGFbeta enhanced expression of TGFbeta1 and ALK5. Unloading of explants for 2 weeks resulted in proteoglycan loss and increased Col10a1 expression. Both loading and exogenous TGFbeta inhibited elevated Col10a1 expression but not proteoglycan loss. CONCLUSION: Our data might imply that in vivo regular physiological loading of articular cartilage leads to enduring TGFbeta signaling and TGFbeta-induced gene expression. We propose a hypothetical model in which loading activates a self-perpetuating system that prevents hypertrophic differentiation of chondrocytes and is crucial for cartilage homeostasis. PMID- 27268944 TI - Improvement of sound source localization abilities in patients bilaterally supplied with active middle ear implants. AB - CONCLUSIONS: Patients, who are bilaterally supplied with active middle ear implants, perform slightly better in sound localization tasks than when unilaterally aided or unaided. OBJECTIVES: To investigate the impact of bilateral use of active middle ear implants on sound source localization in the horizontal plane in patients with a sloping moderate-to-severe hearing loss. METHODS: Ten adults supplied with Med-EL Vibrant Soundbridge systems (VSB) in both ears participated in the study. Four listening conditions were tested: unaided, aided with VSB on left or right ear and on both sides. In each condition the subjects had to judge the direction of broadband noises delivered randomly across a semicircular array of 11 loudspeakers arranged in an anechoic chamber. RESULTS: When unaided or bilaterally aided, the subjects localized on average 40% of the stimuli correct; when unilaterally aided (left or right), this rate dropped to 20 30% in either condition. Precision of sound localization was highest when bilaterally aided, i.e. the mean RMS angular error was 10 degrees , and lowest when unilaterally aided, i.e. 15 degrees . This is in line with bilateral hearing aid users, who show similar performance in sound localization tasks. PMID- 27268945 TI - Determination of ibuprofen, naproxen and diclofenac in aqueous samples using a multi-template molecularly imprinted polymer as selective adsorbent for solid phase extraction. AB - This study describes the application of multi-template molecularly imprinted polymer (MIP) as selective sorbent in the solid-phase extraction (SPE) of naproxen, ibuprofen and diclofenac from wastewater and river water. MIP was synthesized at 70 degrees C by employing naproxen, ibuprofen and diclofenac as multi-templates, ethylene glycol dimethacrylate, 2-vinyl pyridine and toluene as cross-linker, functional monomer and porogen, respectively. Wastewater and river water samples (pH 2.5) were percolated through SPE cartridge packed with 50mg of the MIP. The cartridge was washed with 2mL of methanol-water 10:90% (v:v) prior to elution with 2mL of acetic acid-acetonitrile 20:80% (v:v). Quantification of eluted compounds was performed with high performance liquid chromatography equipped with photo diode array detection. The detection limits were 0.15, 1.00 and 0.63MUgL(-1) for naproxen, ibuprofen and diclofenac, respectively. Recoveries for naproxen, ibuprofen and diclofenac in deionized water spiked at 5 and 50MUgL( 1) were greater than 80%. Ibuprofen was the most frequently detected compound with maximum concentrations of 221, 67.9 and 11.4MUgL(-1) in wastewater influent, effluent and river water, respectively. PMID- 27268946 TI - Prediction of salt effects on protein phase behavior by HIC retention and thermal stability. AB - In the biopharmaceutical industry it is mandatory to know and ensure the correct protein phase state as a critical quality attribute in every process step. Unwanted protein precipitation or crystallization can lead to column, pipe or filter blocking. In formulation, the formation of aggregates can even be lethal when injected into the patient. The typical methodology to illustrate protein phase states is the generation of protein phase diagrams. Commonly, protein phase behavior is shown in dependence of protein and precipitant concentration. Despite using high-throughput methods for the generation of phase diagrams, the time necessary to reach equilibrium is the bottleneck. Faster methods to predict protein phase behavior are desirable. In this study, hydrophobic interaction chromatography retention times were correlated to crystal size and form. High throughput thermal stability measurements (melting and aggregation temperatures), using an Optim((r))2 system, were successfully correlated to glucose isomerase stability. By using hydrophobic interaction chromatography and thermal stability determinations, glucose isomerase conformational and colloidal stability were successfully predicted for different salts in a specific pH range. PMID- 27268947 TI - Coupling ex vivo electroporation of mouse retinas and luciferase reporter assays to assess rod-specific promoter activity. AB - Ex vivo electroporation of mouse retinas is an established tool to modulate gene expression and to study cell type-specific gene expression. Here we coupled ex vivo electroporation to luciferase reporter assays to facilitate the study of rod photoreceptor-specific gene promoters. The activity of the rod-specific proximal bovine rhodopsin promoter was significantly increased in C57BL/6J wild-type retinas at postnatal days 1 and 7 by 3.4-fold and 8.7-fold respectively. In C57BL/6J Nr2e3(rd7/rd7) retinas, where the rod photoreceptor-specific nuclear receptor Nr2e3 is not expressed, a significant increase by 2.5-fold was only observed at postnatal day 7. Cone-specific S-opsin promoter activity was not modulated in C57BL/6J wild-type and Nr2e3(rd7/rd7) retinas. Taken together, we describe an easily implementable protocol to assess rod-specific promoter activity in a physiological context resembling that of the developing postnatal mouse retina. PMID- 27268948 TI - How to train plastic surgeons of the future. AB - INTRODUCTION: Plastic surgery is a competitive and over-subscribed career choice despite minimal medical school exposure. We quantify factors influencing career interest in plastic surgery, speciality appeal and workforce planning. These findings optimise and refine evidence-based plastic surgery training and postgraduate selection criteria. METHODS: Medical students from two national plastic surgery courses complete a post-course questionnaire. Data categories included past experience and career interest in plastic surgery, sources of exposure, motivational factors, and sub-speciality interest. Data were recorded on modified Likert scales, with linear regression and t-test analyses performed. RESULTS: 175 students completed the questionnaire (81% response). Duration of medical student exposure to plastic surgery was significantly associated with career interest (Linear coefficient 0.12, 95% CI 0.08-0.17, P < 0.0001; r(2) = 0.15). 75 h experience is a significant cut-off to categorise students. Mean (95% CI) career interest is 31 percentage points higher in students with >75 h experience (89.2%, 83.2-95.2) compared to students with <=75 h experience (58.1%, 52.9-63.3) (P < 0.0001). Influential sources included: (1) Operating Room (2) Consultant/Attending interaction (3) Resident interaction. Motivational factors towards a career in plastic surgery included operative satisfaction (91%), improving patient quality of life (89%), and reconstructive surgery (88%). Sub speciality interests included: (1) Hand and Upper Limb (28%); (2) Cleft Lip and Palate (26%); (3) Burns (15%). CONCLUSION: This study identified influential and motivational factors upon a career in plastic surgery. Medical student exposure can be tailored to maximise positive educational exposure to optimise evidence based plastic surgery training and workforce planning. PMID- 27268949 TI - Web Health Monitoring Survey: A New Approach to Enhance the Effectiveness of Telemedicine Systems. AB - BACKGROUND: Aging of the European population and interest in a healthy population in western countries have contributed to an increase in the number of health surveys, where the role of survey design, data collection, and data analysis methodology is clear and recognized by the whole scientific community. Survey methodology has had to couple with the challenges deriving from data collection through information and communications technology (ICT). Telemedicine systems have not used patients as a source of information, often limiting them to collecting only biometric data. A more effective telemonitoring system would be able to collect objective and subjective data (biometric parameters and symptoms reported by the patients themselves), and to control the quality of subjective data collected: this goal be achieved only by using and merging competencies from both survey methodology and health research. OBJECTIVE: The objective of our study was to propose new metrics to control the quality of data, along with the well-known indicators of survey methodology. Web questionnaires administered daily to a group of patients for an extended length of time are a Web health monitoring survey (WHMS) in a telemedicine system. METHODS: We calculated indicators based on paradata collected during a WHMS study involving 12 patients, who signed in to the website daily for 2 months. RESULTS: The patients' involvement was very high: the patients' response rate ranged between 1.00 and 0.82, with an outlier of 0.65. Item nonresponse rate was very low, ranging between 0.0% and 7.4%. We propose adherence to the chosen time to connect to the website as a measure of involvement and cooperation by the patients: the difference from the median time ranged between 11 and 24 minutes, demonstrating very good cooperation and involvement from all patients. To measure habituation to the questionnaire, we also compared nonresponse rates to the items between the first and the second month of the study, and found no significant difference. We computed the time to complete the questionnaire both as a measure of possible burden for patient, and to detect the risk of automatic responses. Neither of these hypothesis was confirmed, and differences in time to completion seemed to depend on health conditions. Focus groups with patients confirmed their appreciation for this "new" active role in a telemonitoring system. CONCLUSIONS: The main and innovative aspect of our proposal is the use of a Web questionnaire to virtually recreate a checkup visit, integrating subjective (patient's information) with objective data (biometric information). Our results, although preliminary and if need of further study, appear promising in proposing more effective telemedicine systems. Survey methodology could have an effective role in this growing field of research and applications. PMID- 27268951 TI - Sodium Atom Emission from Aqueous Surfactant Solutions Exposed to Ultrasound. AB - Emission from electronically excited sodium atoms (Na*) was observed when argon saturated aqueous solutions of the anionic surfactants, sodium dodecyl sulfate, sodium octyl sulfate, sodium 1-pentanesulfonate, and sodium 1-octanesulfonate were sonicated using 358 kHz ultrasound. The same emission band, centered at about 590 nm, was also obtained in aqueous NaCl solutions, although a ~100-fold higher concentration than that used for the surfactant solutions was required to obtain an emission of comparable intensity. The results have been interpreted in terms of the surfactant adsorbing at the gas-solution interface of the bubbles generated by the ultrasound, generating an electrostatic surface potential, and attracting Na+ counterions to the bubble surface. It is reasoned that Na+ ions are simultaneously reduced and electronically excited at the bubble-solution interface during the final stages of the collapse phase of the acoustically driven bubble. It is proposed that sodium ion bound water molecules reduce interfacial Na+ under the extreme, perhaps supercritical, conditions the interface experiences on bubble implosion. PMID- 27268950 TI - Comparison of Antigenic Dominants of VP7 in G9 and G1 Rotavirus Strains Circulating in La Rioja, Argentina, with the Vaccine Strains. AB - A massive vaccination in Argentina was implemented recently. The antigenic dominants of VP7 in G9 and G1 rotavirus strains, circulating in La Rioja, Argentina with strain vaccines were compared. From 2000 to 2010 in several attention centers of La Rioja, at northwestern Argentina, 418 stool samples from children younger than 5 years old were collected. Ninety were positive by immunochromatography and 51 were genotyped by reverse transcriptase-polymerase chain reaction followed by nested-multiplex polymerase chain reaction (PCR) with type-specific primers. Six G9 strains and four G1 strains were sequenced by MACROGEN Korea. The phylogenetic analysis was conducted in MEGA 6.0. The 940 bp were aligned using CLUSTALW and the tree was inferred using the UPGMA method. The antigenic dominants of VP7, 7-1a, 7-1b, and 7-2 were studied using BioEdit, 7.2.5. In the comparison between G9-lineage III d rotavirus (RV) strains circulating in La Rioja with ROTAVAC vaccine strain, three differences were detected corresponding to 100, 211, and 145 positions. In the comparison between G1-Lineage 1 strains and G1 Rotarix and G1 RotaTeq, three differences were observed in 94, 123, and 217 positions. All these positions were important for the escape to neutralization for study with monoclonal antibody. In conclusion, the differences between the G1 strains in La Rioja, Argentina and the G1 components of the RotaTeq and Rotarix vaccine strains are few, but important for the escape immunologic, and need to be monitored for appropriate evaluation of long-term impact of vaccine used in Argentina. Nevertheless, the VP7 antigenic regions of G9 RV strains circulating in La Rioja and ROTAVAC vaccine strains are different to other zones of Argentina and could play an important role in the failure of vaccine response in these regions and Argentina. PMID- 27268953 TI - (Almost) Stationary Isotachophoretic Concentration Boundary in a Nanofluidic Channel Using Charge Inversion. AB - The present work is an experimental study of a new means to induce a quasi stationary boundary for concentration or separation in a nanochannel induced by charge inversion. Instead of using pressure-driven counter-flow to keep the front stationary, we exploit charge inversion by a highly charged electrolyte, Ru(bpy)3Cl2, that changes the sign of the zeta potential in part of the channel from negative to positive. Having a non-charge inverting electrolyte (MgCl2) in the other part of the channel and applying an electric field can create a standing front at the interface between them without added dispersion due to an externally applied pressure-driven counterflow. The resulting slow moving front position can be easily imaged optically since Ru(bpy)3Cl2 is fluorescent. A simple analytical model for the velocity field and front axial position that reproduces the experimental location of the front shows that the location can be tuned by changing the concentration of the electrolytes (and thus local zeta potential). Both of these give the charge inversion-mediated boundary significant advantages over current methods of concentration and separation and the method is, therefore, of particular importance to chemical and biochemical analysis systems such as chromatography and separations and for enhancing the stacking performance of field amplified sample injection and isotachophoresis. By choosing a non-charge inverting electrolyte other than MgCl2, either this electrolyte or the Ru(bpy)3Cl2 solution can be made to be the leading or trailing electrolyte. PMID- 27268952 TI - Intensive Care Unit Structure Variation and Implications for Early Mobilization Practices. An International Survey. AB - RATIONALE: Early mobilization (EM) improves outcomes for mechanically ventilated patients. Variation in structure and organizational characteristics may affect implementation of EM practices. OBJECTIVES: We queried intensive care unit (ICU) environment and standardized ICU practices to evaluate organizational characteristics that enable EM practice. METHODS: We recruited 151 ICUs in France, 150 in Germany, 150 in the United Kingdom, and 500 in the United States by telephone. Survey domains included respondent characteristics, hospital and ICU characteristics, and ICU practices and protocols. MEASUREMENTS AND MAIN RESULTS: We surveyed 1,484 ICU leaders and received a 64% response rate (951 ICUs). Eighty-eight percent of respondents were in nursing leadership roles; the remainder were physiotherapists. Surveyed ICUs were predominantly mixed medical surgical units (67%), and 27% were medical ICUs. ICU staffing models differed significantly (P < 0.001 each) by country for high-intensity staffing, nurse/patient ratios, and dedicated physiotherapists. ICU practices differed by country, with EM practices present in 40% of French ICUs, 59% of German ICUs, 52% of U.K. ICUs, and 45% of U.S. ICUs. Formal written EM protocols were present in 24%, 30%, 20%, and 30%, respectively, of those countries' ICUs. In multivariate analysis, EM practice was associated with multidisciplinary rounds (odds ratio [OR], 1.77; P = 0.001), setting daily goals for patients (OR, 1.62; P = 0.02), presence of a dedicated physiotherapist (OR, 2.48; P < 0.001), and the ICU's being located in Germany (reference, United States; OR, 2.84; P < 0.001). EM practice was also associated with higher nurse staffing levels (1:1 nurse/patient ratio as a reference; 1:2 nurse/patient ratio OR, 0.59; P = 0.05; 1:3 nurse/patient ratio OR, 0.33; P = 0.005; 1:4 or less nurse/patient ratio OR, 0.37; P = 0.005). Those responding rarely cited ambulation of mechanically ventilated patients, use of a bedside cycle, or neuromuscular electrical stimulation as part of their EM practice. Physical therapy initiation, barriers to EM practice, and EM equipment were highly variable among respondents. CONCLUSIONS: International ICU structure and practice is quite heterogeneous, and several factors (multidisciplinary rounds, setting daily goals for patients, presence of a dedicated physiotherapist, country, and nurse/patient staffing ratio) are significantly associated with the practice of EM. Practice and barriers may be far different based upon staffing structure. To achieve successful implementation, whether through trials or quality improvement, ICU staffing and practice patterns must be taken into account. PMID- 27268954 TI - Laparoscopic Gastrostomy Is Superior to Percutaneous Endoscopic Gastrostomy Tube Placement in Children Less Than 5 years of Age. AB - PURPOSE: Minimally invasive procedures for enteral access in children have evolved over the years, resulting in various techniques of gastrostomy tube placement. The two most common techniques are laparoscopic gastrostomy (LG) and percutaneous endoscopic gastrostomy (PEG). Our study compares the outcomes of both procedures exclusively in children under the age of five. METHODS: All procedures relating to enteral access in children <5 years of age were reviewed retrospectively from July 2009 to July of 2014 as approved by our Institutional Review Board. Demographics, techniques, and complications were collected and analyzed. RESULTS: Of 293 patients in our study, 150 patients underwent PEG, 75 LG, and 68 LG with Nissen fundoplication (LNG). The most common indication for enteral tube placement was failure to thrive and feeding intolerance. Operative time was less in the PEG group than in the other two groups (P = .001). Overall complication rate was 60% for LG and LNG and 58% for PEG (P = NS). The major complication rate was 3.3% in the PEG group and 0.7% for the LG and LNG groups. There were two deaths in the PEG group. Sixty-eight patients (45.3%) from the PEG group underwent tube changes under anesthesia, requiring additional trip to the operating room with general anesthesia compared with LG and LNG groups (2%) (P = .001). From the PEG group, 134 patients (89%) required many fluoroscopic interventions for tube dislodgments and conversion to gastrojejunostomy tubes for significant reflux and inability to use the gastrostomy (P = .001). CONCLUSION: PEG tubes had a higher major complication rate than LG tubes with or without fundoplication in children <5 years of age. Despite longer operative time, LG seems to be the procedure of choice for children of this age for enteral access. Elimination of unnecessary tube changes under anesthesia and the fluoroscopic interventions after the PEG would be beneficial. PMID- 27268955 TI - Targeting inflammation in diabetic kidney disease: early clinical trials. AB - INTRODUCTION: The age-standardized death rate from diabetic kidney disease increased by 106% from 1990 to 2013, indicating that novel therapeutic approaches are needed, in addition to the renin-angiotensin system (RAS) blockers currently in use. Clinical trial results of anti-fibrotic therapy have been disappointing. However, promising anti-inflammatory drugs are currently on phase 1 and 2 randomized controlled trials. AREAS COVERED: The authors review the preclinical, phase 1 and 2 clinical trial information of drugs tested for diabetic kidney disease that directly target inflammation as a main or key mode of action. Agents mainly targeting other pathways, such as endothelin receptor or mineralocorticoid receptor blockers and vitamin D receptor activators are not discussed. EXPERT OPINION: Agents targeting inflammation have shown promising results in the treatment of diabetic kidney disease when added on top of RAS blockade. The success of pentoxifylline in open label trials supports the concept of targeting inflammation. In early clinical trials, the pentoxifylline derivative CTP-499, the CCR2 inhibitor CCX140-B, the CCL2 inhibitor emapticap pegol and the JAK1/JAK2 inhibitor baricitinib were the most promising drugs for diabetic kidney disease. The termination of trials testing the anti-IL-1beta antibody gevokizumab in 2015 will postpone the evaluation of therapies targeting inflammatory cytokines. PMID- 27268956 TI - Growth Factor-Mediated Migration of Bone Marrow Progenitor Cells for Accelerated Scaffold Recruitment. AB - Tissue engineering approaches using growth factor-functionalized acellular scaffolds to support and guide repair driven by endogenous cells are thought to require a careful balance between cell recruitment and growth factor release kinetics. The objective of this study was to identify a growth factor combination that accelerates progenitor cell migration into self-assembling peptide hydrogels in the context of cartilage defect repair. A novel 3D gel-to-gel migration assay enabled quantification of the chemotactic impact of platelet-derived growth factor-BB (PDGF-BB), heparin-binding insulin-like growth factor-1 (HB-IGF-1), and transforming growth factor-beta1 (TGF-beta1) on progenitor cells derived from subchondral bovine trabecular bone (bone-marrow progenitor cells, BM-PCs) encapsulated in the peptide hydrogel [KLDL]3. Only the combination of PDGF-BB and TGF-beta1 stimulated significant migration of BM-PCs over a 4-day period, measured by confocal microscopy. Both PDGF-BB and TGF-beta1 were slowly released from the gel, as measured using their (125)I-labeled forms, and they remained significantly present in the gel at 4 days. In the context of augmenting microfracture surgery for cartilage repair, our strategy of delivering chemotactic and proanabolic growth factors in KLD may provide the necessary local stimulus to help increase defect cellularity, providing more cells to generate repair tissue. PMID- 27268957 TI - Species and tissues specific differentiation of processed animal proteins in aquafeeds using proteomics tools. AB - The rapidly growing aquaculture industry drives the search for sustainable protein sources in fish feed. In the European Union (EU) since 2013 non-ruminant processed animal proteins (PAP) are again permitted to be used in aquafeeds. To ensure that commercial fish feeds do not contain PAP from prohibited species, EU reference methods were established. However, due to the heterogeneous and complex nature of PAP complementary methods are required to guarantee the safe use of this fish feed ingredient. In addition, there is a need for tissue specific PAP detection to identify the sources (i.e. bovine carcass, blood, or meat) of illegal PAP use. In the present study, we investigated and compared different protein extraction, solubilisation and digestion protocols on different proteomics platforms for the detection and differentiation of prohibited PAP. In addition, we assessed if tissue specific PAP detection was feasible using proteomics tools. All work was performed independently in two different laboratories. We found that irrespective of sample preparation gel-based proteomics tools were inappropriate when working with PAP. Gel-free shotgun proteomics approaches in combination with direct spectral comparison were able to provide quality species and tissue specific data to complement and refine current methods of PAP detection and identification. SIGNIFICANCE: To guarantee the safe use of processed animal protein (PAP) in aquafeeds efficient PAP detection and monitoring tools are required. The present study investigated and compared various proteomics workflows and shows that the application of shotgun proteomics in combination with direct comparison of spectral libraries provides for the desired species and tissue specific classification of this heat sterilized and pressure treated (>=133 degrees C, at 3bar for 20min) protein feed ingredient. PMID- 27268958 TI - Quantitative proteomics analysis using 2D-PAGE to investigate the effects of cigarette smoke and aerosol of a prototypic modified risk tobacco product on the lung proteome in C57BL/6 mice. AB - Smoking is associated with several serious diseases, such as lung cancer and chronic obstructive pulmonary disease (COPD). Within our systems toxicology framework, we are assessing whether potential modified risk tobacco products (MRTP) can reduce smoking-related health risks compared to conventional cigarettes. In this article, we evaluated to what extent 2D-PAGE/MALDI MS/MS (2D PAGE) can complement the iTRAQ LC-MS/MS results from a previously reported mouse inhalation study, in which we assessed a prototypic MRTP (pMRTP). Selected differentially expressed proteins identified by both LC-MS/MS and 2D-PAGE approaches were further verified using reverse-phase protein microarrays. LC MS/MS captured the effects of cigarette smoke (CS) on the lung proteome more comprehensively than 2D-PAGE. However, an integrated analysis of both proteomics data sets showed that 2D-PAGE data complement the LC-MS/MS results by supporting the overall trend of lower effects of pMRTP aerosol than CS on the lung proteome. Biological effects of CS exposure supported by both methods included increases in immune-related, surfactant metabolism, proteasome, and actin cytoskeleton protein clusters. Overall, while 2D-PAGE has its value, especially as a complementary method for the analysis of effects on intact proteins, LC-MS/MS approaches will likely be the method of choice for proteome analysis in systems toxicology investigations. SIGNIFICANCE: Quantitative proteomics is anticipated to play a growing role within systems toxicology assessment frameworks in the future. To further understand how different proteomics technologies can contribute to toxicity assessment, we conducted a quantitative proteomics analysis using 2D PAGE and isobaric tag-based LC-MS/MS approaches and compared the results produced from the 2 approaches. Using a prototypic modified risk tobacco product (pMRTP) as our test item, we show compared with cigarette smoke, how 2D-PAGE results can complement and support LC-MS/MS data, demonstrating the much lower effects of pMRTP aerosol than cigarette smoke on the mouse lung proteome. The combined analysis of 2D-PAGE and LC-MS/MS data identified an effect of cigarette smoke on the proteasome and actin cytoskeleton in the lung. PMID- 27268959 TI - The WRKY57 Transcription Factor Affects the Expression of Jasmonate ZIM-Domain Genes Transcriptionally to Compromise Botrytis cinerea Resistance. AB - Although necrotrophic pathogens cause many devastating plant diseases, our understanding of the plant defense response to them is limited. Here, we found that loss of function of WRKY57 enhanced the resistance of Arabidopsis (Arabidopsis thaliana) against Botrytis cinerea infection. Further investigation suggested that the negative regulation of WRKY57 against B cinerea depends on the jasmonic acid (JA) signaling pathway. Chromatin immunoprecipitation experiments revealed that WRKY57 directly binds to the promoters of JASMONATE ZIM-DOMAIN1 (JAZ1) and JAZ5, encoding two important repressors of the JA signaling pathway, and activates their transcription. In vivo and in vitro experiments demonstrated that WRKY57 interacts with nuclear-encoded SIGMA FACTOR BINDING PROTEIN1 (SIB1) and SIB2. Further experiments display that the same domain, the VQ motif, of SIB1 and SIB2 interact with WRKY33 and WRKY57. Moreover, transient transcriptional activity assays confirmed that WRKY57 and WRKY33 competitively regulate JAZ1 and JAZ5, SIB1 and SIB2 further enhance these competitions of WRKY57 to WRKY33. Therefore, coordinated regulation of Arabidopsis against B cinerea by transcription activators and repressors would benefit plants by allowing fine regulation of defense. PMID- 27268960 TI - Functional Promiscuity of Two Divergent Paralogs of Type III Plant Polyketide Synthases. AB - Plants effectively defend themselves against biotic and abiotic stresses by synthesizing diverse secondary metabolites, including health-protective flavonoids. These display incredible chemical diversity and ubiquitous occurrence and confer impeccable biological and agricultural applications. Chalcone synthase (CHS), a type III plant polyketide synthase, is critical for flavonoid biosynthesis. It catalyzes acyl-coenzyme A thioesters to synthesize naringenin chalcone through a polyketidic intermediate. The functional divergence among the evolutionarily generated members of a gene family is pivotal in driving the chemical diversity. Against this backdrop, this study was aimed to functionally characterize members of the CHS gene family from Rheum emodi, an endangered and endemic high-altitude medicinal herb of northwestern Himalayas. Two full-length cDNAs (1,179 bp each), ReCHS1 and ReCHS2, encoding unique paralogs were isolated and characterized. Heterologous expression and purification in Escherichia coli, bottom-up proteomic characterization, high-performance liquid chromatography electrospray ionization-tandem mass spectrometry analysis, and enzyme kinetic studies using five different substrates confirmed their catalytic potential. Phylogenetic analysis revealed the existence of higher synonymous mutations in the intronless divergents of ReCHS. ReCHS2 displayed significant enzymatic efficiency (Vmax/Km) with different substrates. There were significant spatial and altitudinal variations in messenger RNA transcript levels of ReCHSs correlating positively with metabolite accumulation. Furthermore, the elicitations in the form of methyl jasmonate, salicylic acid, ultraviolet B light, and wounding, chosen on the basis of identified cis-regulatory promoter elements, presented considerable differences in the transcript profiles of ReCHSs. Taken together, our results demonstrate differential propensities of CHS paralogs in terms of the accumulation of flavonoids and their relative substrate selectivities. PMID- 27268961 TI - Herbaceous Angiosperms Are Not More Vulnerable to Drought-Induced Embolism Than Angiosperm Trees. AB - The water transport pipeline in herbs is assumed to be more vulnerable to drought than in trees due to the formation of frequent embolisms (gas bubbles), which could be removed by the occurrence of root pressure, especially in grasses. Here, we studied hydraulic failure in herbaceous angiosperms by measuring the pressure inducing 50% loss of hydraulic conductance (P50) in stems of 26 species, mainly European grasses (Poaceae). Our measurements show a large range in P50 from -0.5 to -7.5 MPa, which overlaps with 94% of the woody angiosperm species in a worldwide, published data set and which strongly correlates with an aridity index. Moreover, the P50 values obtained were substantially more negative than the midday water potentials for five grass species monitored throughout the entire growing season, suggesting that embolism formation and repair are not routine and mainly occur under water deficits. These results show that both herbs and trees share the ability to withstand very negative water potentials without considerable embolism formation in their xylem conduits during drought stress. In addition, structure-function trade-offs in grass stems reveal that more resistant species are more lignified, which was confirmed for herbaceous and closely related woody species of the daisy group (Asteraceae). Our findings could imply that herbs with more lignified stems will become more abundant in future grasslands under more frequent and severe droughts, potentially resulting in lower forage digestibility. PMID- 27268962 TI - Maize and Arabidopsis ARGOS Proteins Interact with Ethylene Receptor Signaling Complex, Supporting a Regulatory Role for ARGOS in Ethylene Signal Transduction. AB - The phytohormone ethylene regulates plant growth and development as well as plant response to environmental cues. ARGOS genes reduce plant sensitivity to ethylene when overexpressed in transgenic Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). A previous genetic study suggested that the endoplasmic reticulum and Golgi-localized maize ARGOS1 targets the ethylene signal transduction components at or upstream of CONSTITUTIVE TRIPLE RESPONSE1, but the mechanism of ARGOS modulating ethylene signaling is unknown. Here, we demonstrate in Arabidopsis that ZmARGOS1, as well as the Arabidopsis ARGOS homolog ORGAN SIZE RELATED1, physically interacts with Arabidopsis REVERSION-TO-ETHYLENE SENSITIVITY1 (RTE1), an ethylene receptor interacting protein that regulates the activity of ETHYLENE RESPONSE1. The protein-protein interaction was also detected with the yeast split ubiquitin two-hybrid system. Using the same yeast assay, we found that maize RTE1 homolog REVERSION-TO-ETHYLENE SENSITIVITY1 LIKE4 (ZmRTL4) and ZmRTL2 also interact with maize and Arabidopsis ARGOS proteins. Like AtRTE1 in Arabidopsis, ZmRTL4 and ZmRTL2 reduce ethylene responses when overexpressed in maize, indicating a similar mechanism for ARGOS regulating ethylene signaling in maize. A polypeptide fragment derived from ZmARGOS8, consisting of a Pro-rich motif flanked by two transmembrane helices that are conserved among members of the ARGOS family, can interact with AtRTE1 and maize RTL proteins in Arabidopsis. The conserved domain is necessary and sufficient to reduce ethylene sensitivity in Arabidopsis and maize. Overall, these results suggest a physical association between ARGOS and the ethylene receptor signaling complex via AtRTE1 and maize RTL proteins, supporting a role for ARGOS in regulating ethylene perception and the early steps of signal transduction in Arabidopsis and maize. PMID- 27268963 TI - Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid. AB - Potential adverse effects of chemical substances on thyroid function are usually examined by measuring serum levels of thyroid-related hormones. Instead, recent risk assessments for thyroid-active chemicals have focussed on iodine uptake inhibition, an upstream event that by itself is not necessarily adverse. Establishing the extent of uptake inhibition that can be considered de minimis, the chosen benchmark response (BMR), is therefore critical. The BMR values selected by two international advisory bodies were 5% and 50%, a difference that had correspondingly large impacts on the estimated risks and health-based guidance values that were established. Potential treatment-related inhibition of thyroidal iodine uptake is usually determined by comparing thyroidal uptake of radioactive iodine (RAIU) during treatment with a single pre-treatment RAIU value. In the present study it is demonstrated that the physiological intra individual variation in iodine uptake is much larger than 5%. Consequently, in treatment RAIU values, expressed as a percentage of the pre-treatment value, have an inherent variation, that needs to be considered when conducting dose-response analyses. Based on statistical and biological considerations, a BMR of 20% is proposed for benchmark dose analysis of human thyroidal iodine uptake data, to take the inherent variation in relative RAIU data into account. Implications for the tolerated daily intakes for perchlorate and chlorate, recently established by the European Food Safety Authority (EFSA), are discussed. PMID- 27268964 TI - Isoledene from Mesua ferrea oleo-gum resin induces apoptosis in HCT 116 cells through ROS-mediated modulation of multiple proteins in the apoptotic pathways: A mechanistic study. AB - Colorectal cancer (CRC) is one of the most common human malignant tumors worldwide. Arising from the transformation of epithelial cells in the colon and/or rectum into malignant cells, the foundation of CRC pathogenesis lies in the progressive accumulation of mutations in oncogenes and tumor-suppressor genes, such as KRAS and APC. Resistance to apoptosis is one of the key mechanisms in the development of CRC as it is for any other kind of cancer. Natural products have been shown to induce the expression of apoptosis regulators that are blocked in cancer cells. In the present study, a series of in vitro assays were employed to study the apoptosis-inducing attributes of Isoledene rich sub-fraction (IR-SF) collected from the oleo-gum resin of M. ferrea. Data obtained, showed that IR-SF inhibited cell proliferation and induced typical apoptotic changes in the overall morphology of all the CRC cell lines tested. Fluorescent staining assays revealed characteristic nuclear condensation, and marked decrease in mitochondrial outer membrane potential in the treated cells. In addition, an increment in the levels of ROS, caspase-8, -9 and -3 was observed. Proteomic analysis revealed that IR-SF up-regulated the expression of pro-apoptotic proteins, i.e., Bid, Bim and cytochrome c. Cytochrome c in turn activated caspases cascade resulting in the induction of apoptosis. Moreover, IR-SF significantly down-regulated Bcl-2, Bcl w, survivin, xIAP and HSPs pro-survival proteins and induced DNA fragmentation and G0/G1-phase arrest in HCT 116 cells. Chemical characterization of IR-SF by GC MS and HPLC methods identified Isoledene as one of the major compounds. Altogether, results of the present study demonstrate that IR-SF may induce apoptosis in human colorectal carcinoma cells through activation of ROS-mediated apoptotic pathways. PMID- 27268965 TI - Predictive Model for the Design of Zwitterionic Polymer Brushes: A Statistical Design of Experiments Approach. AB - The performance of polymer interfaces in biology is governed by a wide spectrum of interfacial properties. With the ultimate goal of identifying design parameters for stem cell culture coatings, we developed a statistical model that describes the dependence of brush properties on surface-initiated polymerization (SIP) parameters. Employing a design of experiments (DOE) approach, we identified operating boundaries within which four gel architecture regimes can be realized, including a new regime of associated brushes in thin films. Our statistical model can accurately predict the brush thickness and the degree of intermolecular association of poly[{2-(methacryloyloxy) ethyl} dimethyl-(3-sulfopropyl) ammonium hydroxide] (PMEDSAH), a previously reported synthetic substrate for feeder-free and xeno-free culture of human embryonic stem cells. DOE-based multifunctional predictions offer a powerful quantitative framework for designing polymer interfaces. For example, model predictions can be used to decrease the critical thickness at which the wettability transition occurs by simply increasing the catalyst quantity from 1 to 3 mol %. PMID- 27268966 TI - Applicability of two automated disintegration apparatuses for rapidly disintegrating (mini)tablets. AB - OBJECTIVES: Orally disintegrating (mini)tablets (OD(M)Ts) are of interest in the field of pharmaceutics. Their orodispersible character is defined by the disintegration time, which is measured with a basket apparatus according to the European Pharmacopoeia. This method, however, lacks applicability for ODTs and especially ODMTs. New disintegration apparatuses have been described in literature, but a qualification to assess the applicability has not been described. A qualification procedure for two automated disintegration apparatuses, OD-mate and Hermes apparatus, is introduced. METHODS: Aspects of the operational qualification as well as precision and accuracy regarding a performance qualification were evaluated for both apparatuses analog to the ICH guideline Q2. While the OQ study is performed separately for each apparatus, accuracy and precision were performed following the same protocol for both testers. KEY FINDINGS: Small RSDs (16.9% OD-mate; 15.2% Hermes compared to 32.3% for the pharmacopeial method) were found despite very fast disintegration times (1.5 s for both apparatuses). By comparing these RSDs to practical examples, the authors propose threshold values for repeatability depending on the mean disintegration time. Obtained results from the qualification were used to assess the applicability of both apparatuses. PMID- 27268967 TI - Application of life cycle assessment for hospital solid waste management: A case study. AB - This study was meant to determine environmental aspects of hospital waste management scenarios using a life cycle analysis approach. The survey for this study was conducted at the largest hospital in a major city of Pakistan. The hospital was thoroughly analyzed from November 2014 to January 2015 to quantify its wastes by category. The functional unit of the study was selected as 1 tonne of disposable solid hospital waste. System boundaries included transportation of hospital solid waste and its treatment and disposal by landfilling, incineration, composting, and material recycling methods. These methods were evaluated based on their greenhouse gas emissions. Landfilling and incineration turned out to be the worst final disposal alternatives, whereas composting and material recovery displayed savings in emissions. An integrated system (composting, incineration, and material recycling) was found as the best solution among the evaluated scenarios. This study can be used by policymakers for the formulation of an integrated hospital waste management plan. IMPLICATIONS: This study deals with environmental aspects of hospital waste management scenarios. It is an increasing area of concern in many developing and resource-constrained countries of the world. The life cycle analysis (LCA) approach is a useful tool for estimation of greenhouse gas emissions from different waste management activities. There is a shortage of information in existing literature regarding LCA of hospital wastes. To the best knowledge of the authors this work is the first attempt at quantifying the environmental footprint of hospital waste in Pakistan. PMID- 27268968 TI - Evaluation of Presto(plus) assay and LightMix kit Trichomonas vaginalis assay for detection of Trichomonas vaginalis in dry vaginal swabs. AB - This is an evaluation study of the Presto(plus) Assay for T. vaginalis by comparing to the TIB MOLBIOL LightMix Kit Trichomonas vaginalis Assay using 615 dry collected vaginal and rectal swabs. Discordant samples were analyzed by the Qiagen(r) Microbial DNA qPCR for TV Assay. Both assays showed comparable performances (McNemar p>0.05). PMID- 27268969 TI - Identification of Metabolites of the Fungicide Penconazole in Human Urine. AB - Penconazole (PEN) is a fungicide used in agriculture that has been classified as hazardous to humans and the environment. The objective of this work was to identify PEN urinary metabolites in humans and propose a biomarker for PEN exposure. Five urine samples were collected from agricultural workers who worked with and were exposed to PEN. Samples were analyzed by liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry, with the source operating in the electrospray ionization mode. Metabolites previously identified in animal studies were searched as possible metabolites in humans. Candidate metabolites were first identified by multiple reaction monitoring following the protonated molecular ions that generated the protonated triazole moiety, which is expected to be present in all PEN metabolites; second, the isotopic patterns of the molecular ions were checked for consistency with the presence of two chlorine atoms; third, the full mass spectra were evaluated for consistency with the molecular structure. Seven different oxidized metabolites were found, both in the free and glucuronide conjugate forms. The major metabolite was the monohydroxyl-derivative PEN-OH (median molar fraction approximately 0.92 as a sum of free and glucuronide conjugated form). The product of further oxidation was the carboxyl-derivate PEN-COOH (median molar fraction approximately 0.03). After hydrolysis with beta-glucuronidase, the free compounds were quantified in the presence of deuterated PEN as an internal standard; PEN-OH levels ranged from 230 to 460 MUg/L, and PEN-COOH levels ranged from 5.2 to 16.7 MUg/L. We propose a pathway for PEN metabolism in humans and suggest PEN-OH, after hydrolysis of glucuronide conjugates, as a biomarker for monitoring human exposure to PEN. PMID- 27268970 TI - Administrative data measured surgical site infection probability within 30 days of surgery in elderly patients. AB - OBJECTIVES: Elderly patients are inordinately affected by surgical site infections (SSIs). This study derived and internally validated a model that used routinely collected health administrative data to measure the probability of SSI in elderly patients within 30 days of surgery. STUDY DESIGN AND SETTING: All people exceeding 65 years undergoing surgery from two hospitals with known SSI status were linked to population-based administrative data sets in Ontario, Canada. We used bootstrap methods to create a multivariate model that used health administrative data to predict the probability of SSI. RESULTS: Of 3,436 patients, 177 (5.1%) had an SSI. The Elderly SSI Risk Model included six covariates: number of distinct physician fee codes within 30 days of surgery; presence or absence of a postdischarge prescription for an antibiotic; presence or absence of three diagnostic codes; and a previously derived score that gauged SSI risk based on procedure codes. The model was highly explanatory (Nagelkerke's R2, 0.458), strongly discriminative (C statistic, 0.918), and well calibrated (calibration slope, 1). CONCLUSION: Health administrative data can effectively determine 30-day risk of SSI risk in elderly patients undergoing a broad assortment of surgeries. External validation is necessary before this can be routinely used to monitor SSIs in the elderly. PMID- 27268971 TI - The rote administrative approach to death in senior housing: Using the other door. AB - Understanding death in long-term care (LTC) facilities and the preexisting standards and policies pertaining to the death experience in LTC is essential. Qualitative interviews were conducted with 10 administrators of CCRCs and data analyzed through content analysis. Results of the current study reveal that administrators spoke of approaching death in their facility similar to any other procedural task, removal of the residents' bodies varied by community, and coordination responsibilities ranged from maintenance crews to management. Notification practices for residents and staff were also inconsistent. Differences existed in internal cultures on providing forms of respect. These practices were standard for some facilities while others were flexible to accommodate family requests. The majority of the sites did not offer additional training on death and dying for staff members. Findings suggest the need for consistency regarding how senior housing administrators approach the death of a resident and provide support for staff members. PMID- 27268972 TI - Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women. AB - BACKGROUND: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. METHODS: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. RESULTS: In premenopausal women, the urinary cadmium level either expressed in MUg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in MUg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. CONCLUSIONS: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women. PMID- 27268973 TI - Efficient decolorization and detoxification of textile industry effluent by Salvinia molesta in lagoon treatment. AB - Salvinia molesta, an aquatic fern was observed to have a potential of degrading azo dye Rubine GFL up to 97% at a concentration of 100mg/L within 72h using 60+/ 2g of root biomass. Both root as well as stem tissues showed induction in activities of the enzymes such as lignin peroxidase, veratryl alcohol oxidase, laccase, tyrosinase, catalase, DCIP reductase and superoxide dismutase during decolorization of Rubine GFL. FTIR, GC-MS, HPLC and UV-visible spectrophotometric analysis confirmed phytotransformation of the model dye into smaller molecules. Analysis of metabolites revealed breakdown of an azo bond of Rubine GFL by the action of lignin peroxidase and laccase and formation of 2-methyl-4-nitroaniline and N-methylbenzene-1, 4-diamine. Anatomical tracing of dye in the stem of S. molesta confirmed the presence of dye in tissues and subsequent removal after 48h of treatment. The concentration of chlorophyll pigments like chlorophyll a, chlorophyll b and carotenoid was observed during the treatment. Toxicity analysis on seeds of Triticum aestivum and Phaseolus mungo revealed the decreased toxicity of dye metabolites. In situ treatment of a real textile effluent was further monitored in a constructed lagoon of the dimensions of 7m*5m*2m (total surface area 35m(2)) using S. molesta for 192h. This large scale treatment was found to significantly reduce the values of COD, BOD5 and ADMI by 76%, 82% and 81% considering initial values 1185, 1440mg/L and 950 units, respectively. PMID- 27268974 TI - The association between wind-related variables and stroke symptom onset: A case crossover study on Jeju Island. AB - BACKGROUND: Although several studies have investigated the effects of ambient temperature on the risk of stroke, few studies have examined the relationship between other meteorological conditions and stroke. Therefore, the aim of this study was to analyze the association between wind-related variables and stroke symptoms onset. METHODS: Data regarding the onset of stroke symptoms occurring between January 1, 2006, and December 31, 2007 on Jeju Island were collected from the Jeju National University Hospital stroke registry. A fixed-strata case crossover analysis based on time of onset and adjusted for ambient temperature, relative humidity, air pressure, and pollutants was used to analyze the effects of wind speed, the daily wind speed range (DWR), and the wind chill index on stroke symptom onset using varied lag terms. Models examining the modification effects by age, sex, smoking status, season, and type of stroke were also analyzed. RESULTS: A total of 409 stroke events (381 ischemic and 28 hemorrhagic) were registered between 2006 and 2007. The odds ratios (ORs) for wind speed, DWR, and wind chill among the total sample at lag 0-8 were 1.18 (95% confidence interval (CI): 1.06-1.31), 1.08 (95% CI: 1.02-1.14), and 1.22 (95% CI: 1.07-1.39) respectively. The ORs for wind speed, DWR, and wind chill for ischemic stroke patients were slightly greater than for patients in the total sample (OR=1.20, 95% CI: 1.08-1.34; OR=1.09, 95% CI: 1.03-1.15; and OR=1.22, 95% CI: 1.07-1.39, respectively). Statistically significant season-specific effects were found for spring and winter, and various delayed effects were observed. In addition, age, sex, and smoking status modified the effect size of wind speed, DWR, and wind chill. CONCLUSIONS: Our analyses showed that the risk of stroke symptoms onset was associated with wind speed, DWR, and wind chill on Jeju Island. PMID- 27268975 TI - What are Head Cavities? - A History of Studies on Vertebrate Head Segmentation. AB - Motivated by the discovery of segmental epithelial coeloms, or "head cavities," in elasmobranch embryos toward the end of the 19th century, the debate over the presence of mesodermal segments in the vertebrate head became a central problem in comparative embryology. The classical segmental view assumed only one type of metamerism in the vertebrate head, in which each metamere was thought to contain one head somite and one pharyngeal arch, innervated by a set of cranial nerves serially homologous to dorsal and ventral roots of spinal nerves. The non segmental view, on the other hand, rejected the somite-like properties of head cavities. A series of small mesodermal cysts in early Torpedo embryos, which were thought to represent true somite homologs, provided a third possible view on the nature of the vertebrate head. Recent molecular developmental data have shed new light on the vertebrate head problem, explaining that head mesoderm evolved, not by the modification of rostral somites of an amphioxus-like ancestor, but through the polarization of unspecified paraxial mesoderm into head mesoderm anteriorly and trunk somites posteriorly. PMID- 27268976 TI - Evolution of the Vertebrate Cranium: Viewed from Hagfish Developmental Studies. AB - Our knowledge of vertebrate cranium evolution has relied largely on the study of gnathostomes. Recent evolutionary and developmental studies of cyclostomes have shed new light on the history of the vertebrate skull. The recent ability to obtain embryos of the hagfish, Eptatretus burgeri, has enabled new studies which have suggested an embryonic morphological pattern (the "cyclostome pattern") of craniofacial development. This pattern is shared by cyclostomes, but not by modern jawed vertebrates. Because this pattern of embryonic head development is thought to be present in some stem gnathostomes (ostracoderms), it is possible that the cyclostome pattern represents the vertebrate ancestral pattern. The study of cyclostomes may thus lead to an understanding of the most ancestral basis of craniofacial development. In this review, we summarize the development of the hagfish chondrocranium in light of the cyclostome pattern, present an updated comparison of the cyclostome chondrocranium, and discuss several aspects of the evolution and development of the vertebrate skull. PMID- 27268977 TI - Effects of Inertial Power and Inertial Force on Bat Wings. AB - The inertial power and inertial force of wings are important factors in evaluating the flight performance of native bats. Based on measurement data of wing size and motions of Eptesicus fuscus, we present a new computational bat wing model with divided fragments of skeletons and membrane. The motions of the model were verified by comparing the joint and tip trajectories with native bats. The influences of flap, sweep, elbow, wrist and digits motions, the effects of different bones and membrane of bat wing, the components on vertical, spanwise and fore-aft directions of the inertial power and force were analyzed. Our results indicate that the flap, sweep, and elbow motions contribute the main inertial power and force; the membrane occupies an important proportion of the inertial power and force; inertial power on flap direction was larger, while variations of inertial forces on different directions were not evident. These methods and results offer insights into flight dynamics in other flying animals and may contribute to the design of future robotic bats. PMID- 27268978 TI - Ontogeny and Sexual Differences in Swimming Proximity to Conspecifics in Response to Visual Cues in Medaka Fish. AB - Adult medaka fish (Oryzias latipes) exhibit complex social behaviors that depend mainly on visual cues from conspecifics. The ontogeny of visually-mediated social behaviors from larval/juvenile to adult medaka fish, however, is unknown. In the present study, we established a simple behavioral paradigm to evaluate the swimming proximity to conspecifics based on visual cues in an inter-individual interaction of two medaka fish throughout life. When two fish were placed separately in a cylindrical tank with a concentric transparent wall, the two fish maintained close proximity to each other. A normal fish inside the tank maintained proximity to an optic nerve-cut fish outside of the tank, while the converse was not true. This behavioral paradigm enabled us to quantify visually induced motivation of a single fish inside the tank. The proximity was detected from larval/juvenile to adult fish. Larval fish, however, maintained close proximity not only to conspecifics, but also to heterospecifics. As the growth stage increased, the degree of proximity to heterospecifics decreased, suggesting that shoaling preferences toward conspecifics and/or visual ability to recognize conspecifics is refined and established according to the growth stage. Furthermore, the proximity of adult female fish was affected by their reproductive status and social familiarity. Only before spawning, adult females maintained closer proximity to familiar males rather than to unfamiliar males, suggesting that proximity was affected by familiarity in a female-specific manner. This simple behavioral paradigm will contribute to our understanding of the neural basis of the development of visually-mediated social behavior using medaka fish. PMID- 27268979 TI - Environmental Enrichment Accelerates the Ontogeny of Cryptic Behavior in Pharaoh Cuttlefish (Sepia pharaonis). AB - We examined effect of environmental enrichment on cuttlefish, the most neutrally advanced invertebrate, to compare species variation of genetic and environmental influences. Cuttlefish were reared from seven to 117 days in one of three environments, namely, "poor" (artificial bottom without objects), "standard" (sandy bottom), and "enriched" (sandy bottom with objects). In Experiment 1, we explored whether enrichment affects the exhibition of crypsis in the cuttlefish. The cuttlefish in the standard and enriched environments spent most of their time at the bottom, exhibiting the mottled or disruptive pattern starting at 27 days of age. On the contrary, those in the poor environment exhibited uniform pattern starting at 87 days of age. Additionally, they repeatedly attempted to dig from 27 to 87 days of age, and moved around by hovering from 77 to 117 days of age. In Experiment 2, we exposed the cuttlefish to six novel substrates every other month after 53 days of age to verify whether enrichment actually affected the maturation of cryptic ability. Cuttlefish from the poor environment tended not to dig into white sandy bottom at 53-55 days of age. Additionally, they did not clearly exhibit appropriate body patterns in response to the six substrates compared to those from the other two environments at 81-83 days of age. However, at 113-115 days of age, most cuttlefish from the three environments exhibited similar cryptic behaviors in response to novel substrates. We conclude that physical enrichment promotes crypsis and accelerates the maturation of this ability in cuttlefish. PMID- 27268980 TI - Vanadium-Binding Ability of Nucleoside Diphosphate Kinase from the Vanadium-Rich Fan Worm, Pseudopotamilla occelata. AB - Polychaete fan worms and ascidians accumulate high levels of vanadium ions. Several vanadiumbinding proteins, known as vanabins, have been found in ascidians. However, no vanadium-binding factors have been isolated from the fan worm. In the present study, we sought to identify vanadiumbinding proteins in the branchial crown of the fan worm using immobilized metal ion affinity chromatography. A nucleoside diphosphate kinase (NDK) homolog was isolated and determined to be a vanadium-binding protein. Kinase activity of the NDK homologue, PoNDK, was suppressed by the addition of V(IV), but was unaffected by V(V). The effect of V(IV) on PoNDK precedes its activation by Mg(II). This is the first report to describe the relationship between NDK and V(IV). PoNDK is located in the epidermis of the branchial crown, and its distribution is very similar to that of vanadium. These results suggest that PoNDK is associated with vanadium accumulation and metabolism in P. occelata. PMID- 27268981 TI - Evolutionary Changes in the Developmental Origin of Hatching Gland Cells in Basal Ray-Finned Fishes. AB - Hatching gland cells (HGCs) originate from different germ layers between frogs and teleosts, although the hatching enzyme genes are orthologous. Teleostei HGCs differentiate in the mesoendodermal cells at the anterior end of the involved hypoblast layer (known as the polster) in late gastrula embryos. Conversely, frog HGCs differentiate in the epidermal cells at the neural plate border in early neurula embryos. To infer the transition in the developmental origin of HGCs, we studied two basal ray-finned fishes, bichir (Polypterus) and sturgeon. We observed expression patterns of their hatching enzyme (HE) and that of three transcription factors that are critical for HGC differentiation: KLF17 is common to both teleosts and frogs; whereas FoxA3 and Pax3 are specific to teleosts and frogs, respectively. We then inferred the transition in the developmental origin of HGCs. In sturgeon, the KLF17, FoxA3, and HE genes were expressed during the tailbud stage in the cell mass at the anterior region of the body axis, a region corresponding to the polster in teleost embryos. In contrast, the bichir was suggested to possess both teleost- and amphibian-type HGCs, i.e. the KLF17 and FoxA3 genes were expressed in the anterior cell mass corresponding to the polster, and the KLF17, Pax3 and HE genes were expressed in dorsal epidermal layer of the head. The change in developmental origin is thought to have occurred during the evolution of basal ray-finned fish, because bichir has two HGCs, while sturgeon only has the teleost-type. PMID- 27268982 TI - Involvement of JunB Proto-Oncogene in Tail Formation During Early Xenopus Embryogenesis. AB - Integration of signaling pathways is important for the establishment of the body plan during embryogenesis. However, little is known about how the multiple signals interact to regulate morphogenesis. Here, we show that junb is expressed in the posterior neural plate and the caudal fin during Xenopus embryogenesis and that overexpression of wild-type JunB induces small head phenotypes and ectopic tail-like structures. A mutant form of JunB that lacked GSK3 and MAPK phosphorylation sites showed stronger tail-like structure-inducing activity than wild-type JunB. Moreover, the mutant JunB induced expression of tailbud and neural marker genes, but not somite and chordoneural hinge (CNH) marker genes in ectopic tail-like structures. In ectodermal explants of Xenopus embryos, overexpression of JunB increased the expression of tailbud and posterior marker genes including fgf3, xbra (t) and wnt8. These results indicate that JunB is capable of inducing the ectopic formation of tissues similar to the tailbud, and that the tailbud-inducing activity of JunB is likely to be regulated by FGF and Wnt pathways. Overall, our results suggest that JunB is a regulator of tail organization possibly through integration of several morphogen signaling pathways. PMID- 27268983 TI - Generation of Albino Cynops pyrrhogaster by Genomic Editing of the tyrosinase Gene. AB - Albino animals are useful for in situ hybridization experiments that demonstrate gene expression in embryos and organs, for the immunological rejection of skin grafts transplanted to host animals, and to identify tissues with regenerative ability during limbs and retina regeneration processes. Cynops pyrrhogaster has extensive regenerating capacities. To facilitate regenerative research, in the present study, we produced albino C. pyrrhogaster using genomic editing. The DNA fragment containing part of the tyrosinase gene from C. pyrrhogaster was amplified using degenerate primers corresponding to evolutionarily conserved nucleotide sequences among several species, and the nucleotide sequence was determined. We designed a transcription activator-like effector nuclease (TALEN) that targets a candidate of the C. pyrrhogaster tyrosinase gene. Fertilized eggs were injected with TALEN mRNA, and albinos of C. pyrrhogaster were obtained. The results of the present study demonstrated that TALEN can be used effectively for genomic editing in C. pyrrhogaster and that the candidates of the tyrosinase gene that were cloned by us are essential for melanin synthesis. The albino newts created in the present study can be used as versatile experimental material. PMID- 27268984 TI - The Feather Structure of Oriental Honey Buzzards (Pernis ptilorhynchus) and Other Hawk Species in Relation to Their Foraging Behavior. AB - The basic structure of a bird feather may be adapted to suit a variety of functions on different parts of the body and in different species. In Oriental honey buzzards (Pernis ptilorhynchus), a species which often preys on the larvae of bees and wasps, it is thought that the bird's integument may provide protection against the stings of these insects. We investigated the structure of Oriental honey buzzard feathers from the face, head, and neck using light and scanning electron microscopy. The structure and appearance of the feathers were compared with those of two other hawk species which live in similar habitats but have different diets: the grey-faced buzzard (Butastur indicus) and the black kite (Milvus migrans). All feathers of Oriental honey buzzards that were examined were smaller than feathers from the same regions of the body of other species and had a reduced number of plumulaceous barbs; barbs were also closer together at the feather tip and had a high barbule density. The small 'scale feathers' on the face had deep barbules with a curved, armor-like appearance, which may help prevent stings from reaching the skin. A unique filamentous substance was observed on all the honey buzzard feathers, particularly those from around the eye of a male bird. It is possible that this may be related to a chemical defense mechanism to deter bees and wasps. PMID- 27268985 TI - Neo-sex Chromosomes in the Maculipennis Species Group (Dichroplus: Acrididae, Melanoplinae): The Cases of D. maculipennis and D. vittigerum. AB - South American melanopline grasshoppers display a disproportionate number of derived karyotypes, including many cases of neo-sex chromosome systems. This is especially true of the genus Dichroplus and its Maculipennis species group. We analyzed the karyotype and neo-sex chromosomes in mitosis and meiosis of Dichroplus maculipennis and D. vittigerum from Argentina using conventional and fluorescent cytogenetic protocols in order to elucidate the behavior and origin of these neo-XY systems in relation to the current phylogeny of this group. Our results showed that D. maculipennis (2n = 22?/22?; neoXY/neoXX) and D. vittigerum, whose karyotype is described here for the first time (2n = 18?/18?; neoXY/neoXX), show highly evolved neo-XY systems, although with significant differences between them. Furthermore, both species differ for two autosomal fixed Robertsonian fusions present in D. vittigerum. Analysis of karyotypic character state optimization strongly suggests the independent origin and evolution of neo-sex systems within this species group. PMID- 27268986 TI - Multiple Neuropeptide-Coding Genes Involved in Planarian Pharynx Extension. AB - Planarian feeding behavior involves three steps: moving toward food, extending the pharynx from their planarian's ventral side after arriving at the food, and ingesting the food through the pharynx. Although pharynx extension is a remarkable behavior, it remains unknown what neuronal cell types are involved in its regulation. To identify neurons involved in regulating pharynx extension, we quantitatively analyzed pharynx extension and sought to identify these neurons by RNA interference (RNAi) and in situ hybridization. This assay, when performed using planarians with amputation of various body parts, clearly showed that the head portion is indispensable for inducing pharynx extension. We thus tested the effects of knockdown of brain neurons such as serotonergic, GABAergic, and dopaminergic neurons by RNAi, but did not observe any effects on pharynx extension behavior. However, animals with RNAi of the Prohormone Convertase 2 (PC2, a neuropeptide processing enzyme) gene did not perform the pharynx extension behavior, suggesting the possible involvement of neuropeptide(s in the regulation of pharynx extension. We screened 24 neuropeptide-coding genes, analyzed their functions by RNAi using the pharynx extension assay system, and identified at least five neuropeptide genes involved in pharynx extension. These was expressed in different cells or neurons, and some of them were expressed in the brain, suggesting complex regulation of planarian feeding behavior by the nervous system. PMID- 27268987 TI - Gonadal Morphology and Gametogenesis in Japanese Red Coral Corallium japonicum (Octocorallia: Alcyonacea) Collected off Cape Ashizuri, Japan. AB - Colonies of the Japanese red coral Corallium japonicum Kishinouye, 1903 collected off Cape Ashizuri, Japan were gonochoric and produced gonads in siphonozooids annually, mainly during the spring season. Polyp anatomy, gonadal morphology and gametogenesis in this species were revealed by light and electron microscopy. A siphonozooid had a pharynx with a prominent siphonoglyph and eight mesenteries: two sulcal, two asulcal, and four lateral. A rudimentary retractor was found on one side of each mesoglea of these mesenteries. The retractor arrangement in the siphonozooid was reverse of what was described in the autozooids of octocorals. Gonads initiated as small protrusions on the mesenteries, except in the asulcal ones, and even at an incipient stage they were covered with a sac-shaped thin layer of mesoglea, which was continuous with the mesoglea of mesenteries. Gastrodermis enveloped the complete outer surface of the thin layer of mesoglea throughout gametogenesis in both oocytes and sperm cysts. Oocytes produced many microvilli on their cortical surfaces beneath the thin layer of mesoglea concomitantly with the accumulation of lipid globules in the cells, whereas in sperm cysts spermatocytes and spermatids increased in number without microvilli production, followed by synchronous spermiogenesis involving remarkable changes in the shape and position of organelles. Based on the comparison of patterns in gonadal development between octocorals including C. japonicum, hexacorals and scyphozoans, octocoral and stauromedusa species may be characterized by the fact that gametogenesis never occurs in the matrix of mesoglea, but rather exclusively within the thin sac of mesoglea surrounded by gastrodermis. PMID- 27268989 TI - Custom, taste and science: Raising chickens in the Pearl River Delta Region, South China. AB - In this paper, I examine chicken husbandry as practised in an immigrant village located in the north-western sector of Hong Kong's New Territories-the southern extension of the Pearl River Delta. People in South China use whole chickens as offerings in rituals and as banquet food. Demand for fresh, flavourful, whole chickens dominates the ways in which chickens are raised and sold in this region. Chicken farming is a highly competitive industry. The supply of birds from individual farms directly and immediately affects the market price, making neighbouring farms potential competitors with one another. On the other hand, diseases that kill the birds can easily spread from one farm to another, making the farmers inter-dependent in an environmental sense. It is the practice of poultry farmers not to visit their neighbours at home on the farm. Co-operation in respect to husbandry is minimal. This social structure effectively eliminates the spread of infectious diseases, but has contributed to the cellularization of households, fostering a loosely organized local community. The outbreak of avian flu, however, has created threats to and opportunities for chicken production, thus promoting co-operation and division of labour among chicken farmers. PMID- 27268988 TI - Asian flus in ethnographic and political context: A biosocial approach. AB - This collection highlights some of the social, cultural, political and economic factors that must be considered in developing a biosocial approach to pandemic influenza control and prevention. To date, most discussions of the current spread of avian influenza and a predicted human influenza pandemic have lacked rigorous analysis of the local contexts in which flus arise and in which the effects of a pandemic would most strongly be felt. Such local engagement is necessary to the development of an effective and ethical programme of epidemic control. The papers in this special issue take a step towards filling this gap by exploring the local moral worlds associated with avian influenza in China, Indonesia and Thailand. PMID- 27268990 TI - Surviving the crisis: Adaptive wisdom, coping mechanisms and local responses to avian influenza threats in Haining, China. AB - Based on ethnographic research conducted in the summer of 2006, this paper examines local responses to the imminent threat of avian flu in Haining County of Zhejiang Province. During our field investigation, we conducted interviews with officials from local medical institutions (including the hospitals, the animal husbandry and veterinary station, and health clinics), to bureaus of public health and agro-economy. We also visited chicken farms, restaurants and farming households. We address the following factors that commonly structured the perceptions and actions of different social actors in the area of study: The changing mode of information-sharing and communication practices in the local communities; the official drive to professionalize the emergency response management system in the county; and the coping mechanisms that helped the villagers and town residents to weather the storm of avian flu. Our field research suggests that collective survival consciousness was translated into a spirit of voluntarism during the crisis. One important practical lesson we have learned from this study is that the adaptive wisdom embedded in local memories demonstrated its operational worth as a resourceful knowledge base for ordinary farmers to deal with food shortage, famine, plague and future pandemics. PMID- 27268991 TI - Community response to avian flu in Central Java, Indonesia. AB - This pilot study suggests that it is more appropriate to think of avian flu as a bio-social and bio-political challenge for Indonesia than merely an epidemiological challenge involving a disease of zoonotic origin. Our examination of popular perceptions of avian flu in Central Java reveals important differences of opinion about which types of fowl are responsible for avian flu transmission and the degree of risk H5N1 poses to humans. The opinions of backyard farmers and commercial poultry farmers are motivated by different forms of practical logic and are differentially influenced by media accounts, government education programmes, foreign aid and rumours about who stands to profit from the disease. Rumours reflect collective anxieties about globalization, the agenda of big business and the trustworthiness of the national government. We also illustrate how a commodity chain analysis can assist in the identification of different stake-holders in the informal and formal poultry industries. The position of each stake-holder needs to be considered in any comprehensive investigation of avian flu. An economic analysis of the capital investment of stake-holders provides insight into how each responds to government directives about the reporting of dead chickens, vaccinating birds etc. Finally, we call for research on avian flu preparedness attentive to Indonesia's de-centralized form of political rule and the social organization of communities so that clear lines of communication and command can be established and mutual assistance mobilized. PMID- 27268992 TI - Ethnography of epidemiologic transition: Avian flu, global health politics and agro-industrial capitalism in Thailand. AB - This paper situates the ethnography of avian flu within the geo-political context of a new epidemiologic transition. Drawing on anthropological experience and insight, this paper examines areas of enquiry in which an ethnographic approach could contribute to a better implementation of prevention and control measures. Within the context of newly emerging diseases and accelerated globalization, the task of ethnography needs to extend far beyond the local. This paper reveals two major global issues that the ethnography of epidemiologic transition must take into consideration: (1) Global agro-industrial capitalism, and (2) global politics in the context of international health organizations and multi-national drug companies. The case of Thailand poses a question of how the strength of ethnographic practice could be deployed to account for the reality of the global local interface of the new epidemiologic transition. PMID- 27268993 TI - Institutional responses to avian influenza in Thailand: Control of outbreaks in poultry and preparedness in the case of human-to-human transmission. AB - Thailand faced an outbreak of H5N1 avian influenza in poultry and in humans in early 2004. By the end of the same year, more than 62 million birds had died or been culled and 17 human cases, with 12 dead, had been detected. Among the human cases, most people were infected via direct contact with ill or deceased poultry, or when living in households with abnormal poultry deaths. One family cluster with probable human-to-human transmission was identified in September 2004. Recognizing the threat of avian and pandemic influenza, the Thai Government endorsed a three-year national strategic plan for 2005-7 with a total budget of 120 million US dollars. In accordance with the national strategic plan, the institutional response was implemented to improve the bio-security of poultry raising, including active surveillance and rapid control of animal and human outbreaks via grassroots participation. The country also started its minimum stockpiling for essential drugs and supplies, with a surge capacity to care for patients if a pandemic should occur. PMID- 27268994 TI - What to do about antimicrobial resistance. PMID- 27268995 TI - Health Care Ergonomics: Contributions of Thomas Waters. AB - OBJECTIVE: The aim of this study was to assess the contributions of Thomas Waters's work in the field of health care ergonomics and beyond. BACKGROUND: Waters's research of safe patient handling with a focus on reducing musculoskeletal disorders (MSDs) in health care workers contributed to current studies and prevention strategies. He worked with several groups to share his research and assist in developing safe patient handling guidelines and curriculum for nursing students and health care workers. METHODS: The citations of articles that were published by Waters in health care ergonomics were evaluated for quality and themes of conclusions. Quality was assessed using the Mixed Methods Appraisal Tool and centrality to original research rating. Themes were documented by the type of population the citing articles were investigating. RESULTS: In total, 266 articles that referenced the top seven cited articles were evaluated. More than 95% of them were rated either medium or high quality. The important themes of these citing articles were as follows: (a) Safe patient handling is effective in reducing MSDs in health care workers. (b) Shift work has negative impact on nurses. (c) There is no safe way to manually lift a patient. (d) Nurse curriculums should contain safe patient handling. CONCLUSION: The research of Waters has contributed significantly to the health care ergonomics and beyond. His work, in combination with other pioneers in the field, has generated multiple initiatives, such as a standard safe patient-handling curriculum and safe patient handling programs. PMID- 27268996 TI - Leveraging Health Care Simulation Technology for Human Factors Research: Closing the Gap Between Lab and Bedside. AB - OBJECTIVE: We describe health care simulation, designed primarily for training, and provide examples of how human factors experts can collaborate with health care professionals and simulationists-experts in the design and implementation of simulation-to use contemporary simulation to improve health care delivery. BACKGROUND: The need-and the opportunity-to apply human factors expertise in efforts to achieve improved health outcomes has never been greater. Health care is a complex adaptive system, and simulation is an effective and flexible tool that can be used by human factors experts to better understand and improve individual, team, and system performance within health care. METHOD: Expert opinion is presented, based on a panel delivered during the 2014 Human Factors and Ergonomics Society Health Care Symposium. RESULTS: Diverse simulators, physically or virtually representing humans or human organs, and simulation applications in education, research, and systems analysis that may be of use to human factors experts are presented. Examples of simulation designed to improve individual, team, and system performance are provided, as are applications in computational modeling, research, and lifelong learning. CONCLUSION: The adoption or adaptation of current and future training and assessment simulation technologies and facilities provides opportunities for human factors research and engineering, with benefits for health care safety, quality, resilience, and efficiency. APPLICATION: Human factors experts, health care providers, and simulationists can use contemporary simulation equipment and techniques to study and improve health care delivery. PMID- 27268997 TI - A conserved dimorphism-regulating histidine kinase controls the dimorphic switching in Paracoccidioides brasiliensis. AB - Paracoccidioides brasiliensis and P. lutzii, thermally dimorphic fungi, are the causative agents of paracoccidioidomycosis (PCM). Paracoccidioides infection occurs when conidia or mycelium fragments are inhaled by the host, which causes the Paracoccidioides cells to transition to the yeast form. The development of disease requires conidia inside the host alveoli to differentiate into yeast cells in a temperature-dependent manner. We describe the presence of a two component signal transduction system in P. brasiliensis, which we investigated by expression analysis of a hypothetical protein gene (PADG_07579) that showed high similarity with the dimorphism-regulating histidine kinase (DRK1) gene of Blastomyces dermatitidis and Histoplasma capsulatum This gene was sensitive to environmental redox changes, which was demonstrated by a dose-dependent decrease in transcript levels after peroxide stimulation and a subtler decrease in transcript levels after NO stimulation. Furthermore, the higher PbDRK1 levels after treatment with increasing NaCl concentrations suggest that this histidine kinase can play a role as osmosensing. In the mycelium-yeast (M->Y) transition, PbDRK1 mRNA expression increased 14-fold after 24 h incubation at 37 degrees C, consistent with similar observations in other virulent fungi. These results demonstrate that the PbDRK1 gene is differentially expressed during the dimorphic M->Y transition. Finally, when P. brasiliensis mycelium cells were exposed to a histidine kinase inhibitor and incubated at 37 degrees C, there was a delay in the dimorphic M->Y transition, suggesting that histidine kinases could be targets of interest for PCM therapy. PMID- 27268998 TI - Sonography of Gastrointestinal Tract Diseases: Correlation With Computed Tomographic Findings and Endoscopy. AB - Sonographic evaluation of the gastrointestinal (GI) tract may be difficult because of overlying intraluminal bowel gas and gas-related artifacts. However, in the absence of these factors and with the development of high-resolution scanners and the technical experience of radiologists, sonography can become a powerful tool for GI tract assessment. This pictorial essay focuses on sonographic findings of GI tract lesions compared with endoscopic, computed tomographic, and magnetic resonance imaging findings. Neoplastic and non neoplastic diseases and postoperative complications are illustrated, and the distinctive sonographic characteristics of these entities are highlighted. PMID- 27268999 TI - A Survey of Ultrasound Milestone Incorporation Into Emergency Medicine Training Programs. AB - OBJECTIVES: With the introduction of the Emergency Medicine Milestone Project in 2013, residencies now assess emergency ultrasound (US) skills at regular intervals. However, it is unclear how programs are implementing the emergency US milestones and assessing competency. With the use of the milestone tool, a survey was distributed to emergency US educators to determine when programs are providing emergency US education, when residents are expected to attain competency, and whether the milestones reflect their expectations of trainees. METHODS: We conducted a prospective cross-sectional survey study distributed electronically to designated emergency US experts at 169 programs. Participants were queried on education and competency evaluation within the context of the milestones by designating a postgraduate year when the 5 milestone levels were taught and competency was expected. Survey findings were reported as percentages of total respondents from descriptive statistics. RESULTS: Responses were received from 53% of programs, and 99% were familiar with the milestones. Most programs provide level 1 (88%) and 2 (85%) instruction during postgraduate year 1. Most programs expect level 1 competency before residency (61%) and expect mastery of level 2 by the end of postgraduate year 1 (60%). Sixty-two percent believe the milestones do not accurately reflect their expectations, citing insufficient minimum scan numbers, lack of specificity, and unattainable level 5 requirements. CONCLUSIONS: There is substantial variability in the frequency and methods of competency evaluation using the emergency US milestones. However, most responders agree that residents should obtain level 2 competency by postgraduate year 1. Variation exists regarding what year and what skills define level 3 or greater competency. PMID- 27269000 TI - A Simple Rule for Prenatal Diagnosis of Total Anomalous Pulmonary Venous Return. AB - The objective of this series was to describe a simple rule for prenatal diagnosis of total anomalous pulmonary venous return (TAPVR). Fourteen fetuses had a prenatal diagnosis of TAPVR by the simple rule, including the following components: (1) the major criterion, which was the absence of a connection between the pulmonary vein and the left atrium; and (2) at least 1 of the following minor criteria: (a) the presence of a vascular confluence behind the atria, (b) abnormal spectral Doppler waveforms in the pulmonary veins, (c) a smooth posterior wall of the left atrium, (d) increased retroatrial space, (e) a dilated coronary sinus (cardiac type), (f) a dilated superior vena cava or brachiocephalic vein, and (g) an additional vessel on the 3-vessel/3-vessel and trachea view or a vertical descending vein. All were accurately diagnosed, and none were missed by the diagnosis. In summary, the simple rule described is helpful in increasing the number of accurate prenatal diagnoses of TAPVR. PMID- 27269001 TI - Use of Targeted Neonatal Echocardiography and Focused Cardiac Sonography in Tertiary Neonatal Intensive Care Units: Time to Embrace It? AB - Focused cardiac sonography and targeted neonatal echocardiography refer to goal directed cardiac imaging using ultrasound, typically by noncardiologic specialists. Although the former consists of a rapid qualitative assessment of cardiac function, which is usually performed by acute care practitioners, the latter refers to detailed functional echocardiography to obtain quantitative and qualitative indexes of pulmonary and systemic hemodynamics in sick neonates and is typically performed by neonatologists. Although the use of these modalities is increasing, they still remain unavailable in most North American centers providing acute care to neonates, partly because of limited data regarding their direct impact on patient care. Here we present a series of 5 cases from a large perinatal unit in which immediate availability of relevant expertise led to important and arguably life-saving clinical interventions. In 4 of these cases, focused cardiac sonography was sufficient to make the diagnosis, whereas in 1 case, clinical integration of detailed systemic hemodynamics measured on target neonatal echocardiography was required. PMID- 27269002 TI - A Novel Semiautomated Fractional Limb Volume Tool for Rapid and Reproducible Fetal Soft Tissue Assessment. AB - The purpose of this study was to document the reproducibility and efficiency of a semiautomated image analysis tool that rapidly provides fetal fractional limb volume measurements. Fifty pregnant women underwent 3-dimensional sonographic examinations for fractional arm and thigh volumes at a mean menstrual age of 31.3 weeks. Manual and semiautomated fractional limb volume measurements were calculated, with the semiautomated measurements calculated by novel software (5D Limb Vol; Samsung Medison, Seoul, Korea). The software applies an image transformation method based on the major axis length, minor axis length, and limb center coordinates. A transformed image is used to perform a global optimization technique for determination of an optimal limb soft tissue boundary. Bland-Altman analysis defined bias with 95% limits of agreement (LOA) between methods, and timing differences between manual versus automated methods were compared by a paired t test. Bland-Altman analysis indicated an acceptable bias with 95% LOA between the manual and semiautomated methods: mean arm volume +/- SD, 1.7% +/- 4.6% (95% LOA, -7.3% to 10.7%); and mean thigh volume, 0.0% +/- 3.8% (95% LOA, 7.5% to 7.5%). The computer-assisted software completed measurements about 5 times faster compared to manual tracings. In conclusion, semiautomated fractional limb volume measurements are significantly faster to calculate when compared to a manual procedure. These results are reproducible and are likely to reduce operator dependency. The addition of computer-assisted fractional limb volume to standard biometry may improve the precision of estimated fetal weight by adding a soft tissue component to the weight estimation process. PMID- 27269003 TI - Repeatability of Junctional Zone Measurements Using 3-Dimensional Transvaginal Sonography in Healthy Fertile Women. AB - OBJECTIVES: To describe the junctional zone and determine the intraobserver and interobserver repeatability of junctional zone measurements using 3-dimensional (3D) transvaginal sonography in healthy fertile women. METHODS: We examined 82 consecutive women with 3D transvaginal sonography. The maximum and minimum junctional zone thickness was measured in all uterine walls. The difference between maximum and minimum thickness and average measurements (maximum thickness + minimum thickness/2) of the anterior, posterior, fundal, and lateral walls were calculated. Among the first 40 consecutive women, intraobserver and interobserver repeatability was evaluated according to the Bland-Altman method and expressed as a coefficient of repeatability. RESULTS: Using 3D transvaginal sonography, we visualized a thin and regular junctional zone in most women. The posterior uterine wall had the largest median maximum junctional zone thickness value of 5.2 (interquartile range, 3.8-6.5) mm. Ten women (12%) had maximum thickness values of 8.0 to 12.0 mm. The maximum thickness in each uterine wall had intraobserver and interobserver coefficients of repeatability of +/-2.1 to +/-3.4 and +/-2.6 to +/-3.9 mm, respectively, which were reduced by average measurements: +/-1.9 and +/-2.0 mm (anterior and posterior walls) and +/-1.5 mm (fundal and lateral walls) for intraobserver and interobserver values. Correlations between measurements were poor in the narrow range of junctional zone thickness. CONCLUSIONS: The junctional zone has an indistinct outline on 3D transvaginal sonography, resulting in measurement errors within a broad range of +/-2 to +/-4 mm, which were only reduced to some extent by average measurements. The thickness of the junctional zone varied within a narrow range in this healthy fertile population, and reliability measurements of junctional zone thickness have to be evaluated in women with a wider range of thickness. The observer repeatability and reliability of junctional zone measurements need to be further evaluated and refined before applying this method in clinical practice. PMID- 27269004 TI - Effect of captopril and telmisartan on methotrexate-induced hepatotoxicity in rats: impact of oxidative stress, inflammation and apoptosis. AB - Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARgamma) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats. Results of the present study revealed MTX-induced hepatotoxicity as demonstrated by increased level of liver enzymes and confirmed by histopathology. Pretreatment with captopril or telmisartan produced a significant hepatic protection manifested as a significant (p < 0.05) decrease in serum levels of alanine transferase (ALT) and aspartate transferase (AST) and alkaline phosphatase (ALP) enzymes; hepatic malondialdehyde (MDA) and total nitrites and nitrates (NOx) levels; as well as a significant increase in hepatic superoxide dismutase (SOD) activity. In addition, there was a remarkable improvement in the histopathological features and a significant reduction in the expression of COX 2, iNOS and caspase-3 enzymes as compared with the MTX group. We recommend considering captopril/Telmisartan, if tolerated and not contraindicated, as preferable antihypertensive agents in patients receiving MTX in their chemotherapy protocols. PMID- 27269005 TI - Sluggish Cognitive Tempo: Sociodemographic, Behavioral, and Clinical Characteristics in a Population of Catalan School Children. AB - OBJECTIVE: The aims of the present study were to examine the presence of sluggish cognitive tempo (SCT) symptoms in children; associations of the symptoms with sociodemographic characteristics of the children; and relationships between SCT symptoms and symptoms of ADHD, dyslexia, academic performance, and behavioral problems. METHOD: We evaluated Catalan schoolchildren aged 7 to 10 years in Barcelona, 2012-2013. Parents filled out the SCT-Child Behavior Checklist (SCT CBCL), the Strengths and Difficulties Questionnaire (SDQ), and a questionnaire concerning sociodemographic characteristics. Teachers completed the ADHD criteria of Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) (ADHD- DSM-IV), a list of dyslexia symptoms, and evaluated the children's academic performance. SCT symptoms were studied as a continuous and dichotomous variable. RESULTS: In all, 11% of the children in our sample scored above the clinical cut off on the SCT-CBCL scale. We observed a higher rate of SCT symptoms in boys, children whose father was unemployed, those whose maternal educational level was lower, children with a high socioeconomic vulnerability index at home, those who reported maternal smoking during pregnancy and current second-hand smoke exposure at home, and children with an ADHD diagnosis. More SCT symptoms were associated with inattention symptoms, symptoms of dyslexia, academic problems, and emotional and peer relationship problems. CONCLUSION: We observed a higher prevalence of SCT symptoms in our sample than expected in the general population. While girls are less prone to SCT symptoms, some socioeconomic indicators, dyslexia, and inattention symptoms as well as exposure to smoking at home increase the risk of SCT and must be taken into account during assessments. PMID- 27269006 TI - Functioning of Young Adults With ADHD in the Military. AB - OBJECTIVE: To assess the functioning of young adults with ADHD in a military setting. METHOD: In all, 14,655 young adults with ADHD (mean age at first examination 17.8 +/- 0.7) attending mandatory service in the Israeli military were compared with matched controls on several functioning domains. RESULTS: Young adults with ADHD had more sessions with mental health care professionals, physician appointments, sick days, and disqualifications of professions than controls ( p < .001). Young adults with ADHD were also less medically fit for combat service (odds ratio [OR] = 0.75, 95% confidence interval [CI] = [0.72, 0.79]), more medically unfit for military service in general (OR = 1.26, 95% CI = [1.13, 1.40]), and had higher rates of overweight and obesity ( p < .001). In addition, they were more likely to be diagnosed with a personality disorder (OR = 1.29, 95% CI = [1.07, 1.53]) or with minor affective and anxiety disorders (OR = 1.33, 95% CI = [1.06, 1.67]) than matched controls. CONCLUSION: These results support a negative effect of ADHD on the functioning of young adults in a military setting. PMID- 27269007 TI - Rates of Intimate Partner Violence Perpetration and Victimization Among Adults With ADHD. AB - OBJECTIVE: Research has demonstrated an association between ADHD and intimate partner violence (IPV). However, it is unclear whether adults with ADHD persisting from childhood are especially at risk, and whether ADHD is a unique risk factor beyond well-established predictors of IPV. METHOD: Adults with (n = 95) and without childhood histories of ADHD (n = 121) who were recruited from Amazon's Mechanical Turk reported their levels of IPV perpetration and victimization, and provided data on additional risk factors of IPV (e.g., childhood maltreatment, alcohol abuse). RESULTS: While controlling for additional risk factors, adults diagnosed with ADHD as children, particularly those with elevated current ADHD symptoms (ADHD-Persist), reported higher rates of IPV perpetration and victimization than adults with ADHD histories but low current symptoms (ADHD-Desist) and adults who were never diagnosed with ADHD (control). CONCLUSION: Adults with ADHD histories and elevated current symptoms are most likely to report IPV perpetration and victimization. PMID- 27269008 TI - Behavioral Health. PMID- 27269009 TI - Focus On Behavioral Health. AB - Long stigmatized, behavioral health conditions are finally becoming a focal point not just for policy makers but also in public discussions about the well-being of the United States. This is in part because of a rising opioid epidemic; the concentration of people with mental illnesses in prisons and jails; and a greater appreciation of the toll taken by depression and other mental disorders on individuals, families, and the economy. The United States spends more on mental health and addiction than on any other medical condition, including heart disease, trauma, and cancer. Within this spending, there's been a shift toward outpatient and other types of community treatment and away from inpatient care. Meanwhile, the Affordable Care Act has made it possible for more people with serious mental illnesses to obtain care, but treatment rates for racial and ethnic minorities still trail those of whites. PMID- 27269011 TI - US Veterans' Use Of VA Mental Health Services And Disability Compensation Increased From 2001 To 2010. AB - There has been concern about the capacity of the Department of Veterans Affairs (VA) health care system to provide care for veterans returning from war zones in the Middle East and Afghanistan. We used two nationally representative surveys of US veterans in 2001 and 2010 to examine changes in the veteran population and veterans' use of health care services after a decade of war. The population was older and more diverse in 2010 than in 2001. In both years, veterans who served in the World War II era or earlier were more likely to have been exposed to combat-related trauma than veterans of more recent service eras. In 2010 veterans who served in the Persian Gulf War era (1990 through the wars in Iraq and Afghanistan) were more likely to have used VA mental health services and to have received VA disability compensation than veterans of previous service eras. Compared to veterans in 2001, those in 2010 were two times more likely to have used any VA health services and were more likely to have received VA disability compensation. These findings highlight changes in the veteran population over time that are important to consider in planning for future VA services. PMID- 27269010 TI - Insurance Financing Increased For Mental Health Conditions But Not For Substance Use Disorders, 1986-2014. AB - This study updates previous estimates of US spending on mental health and substance use disorders through 2014. The results reveal that the long-term trend of greater insurance financing of mental health care continued in recent years. The share of total mental health treatment expenditures financed by private insurance, Medicare, and Medicaid increased from 44 percent in 1986 to 68 percent in 2014. In contrast, the share of spending for substance use disorder treatment financed by private insurance, Medicare, and Medicaid was 45 percent in 1986 and 46 percent in 2014. From 2004 to 2013, a growing percentage of adults received mental health treatment (12.6 percent and 14.6 percent, respectively), albeit only because of the increased use of psychiatric medications. In the same period, only 1.2-1.3 percent of adults received substance use disorder treatment in inpatient, outpatient, or residential settings, although the use of medications to treat substance use disorders increased rapidly. PMID- 27269012 TI - Rapid Growth Of Antipsychotic Prescriptions For Children Who Are Publicly Insured Has Ceased, But Concerns Remain. AB - The rapid growth of antipsychotic medication use among publicly insured children in the early and mid-2000s spurred new state efforts to monitor and improve prescription behavior. A starting point for many oversight initiatives was the foster care system, where most of the children are insured publicly through Medicaid. To understand the context and the effects of these initiatives, we analyzed patterns and trends in antipsychotic treatment of Medicaid-insured children in foster care and those in Medicaid but not in foster care. We found that the trend of rapidly increasing use of antipsychotics appears to have ceased since 2008. Children in foster care treated with antipsychotic medications are now more likely than other Medicaid-insured children to receive psychosocial interventions and metabolic monitoring for the side effects of the medications. However, challenges persist in increasing safety monitoring and access to psychosocial treatment. Development of specialized managed care plans for children in foster care represents a promising policy opportunity. New national quality measures for safe and judicious antipsychotic medication use are also now available to guide improvement. Oversight policies developed for foster care appear to have potential for adaptation to the broader population of Medicaid covered children. PMID- 27269013 TI - Building The Mental Health Workforce Capacity Needed To Treat Adults With Serious Mental Illnesses. AB - There are widespread shortages of mental health professionals in the United States, especially for the care of adults with serious mental illnesses. Such shortages are aggravated by maldistribution of mental health professionals and attractive practice opportunities treating adults with less severe conditions. The Affordable Care Act (ACA) and legislation extending mental health parity coverage are contributing to an increasing demand for mental health services. I consider four policy recommendations to reinvigorate the mental health workforce to meet the rising mental health care demand by adults with serious mental illnesses: expanding loan repayment programs for mental health professionals to practice in underserved areas; raising Medicaid reimbursement for treating serious mental illness; increasing training opportunities for social workers in relevant evidence-based psychosocial services; and disseminating service models that integrate mental health specialists as consultants in general medical care. Achieving progress in attracting mental health professionals to care for adults with serious mental illnesses will require vigorous policy interventions. PMID- 27269014 TI - Removing Obstacles To Eliminating Racial And Ethnic Disparities In Behavioral Health Care. AB - Despite decades of research, racial and ethnic disparities in behavioral health care persist. The Affordable Care Act expanded access to behavioral health care, but many reform initiatives fail to consider research about racial/ethnic minorities. Mistaken assumptions that underlie the expansion of behavioral health care run the risk of replicating existing service disparities. Based on a review of relevant literature and numerous observational and field studies with minority populations, we identified the following three mistaken assumptions: Improvement in health care access alone will reduce disparities, current service planning addresses minority patients' preferences, and evidence-based interventions are readily available for diverse populations. We propose tailoring the provision of care to remove obstacles that minority patients face in accessing treatment, promoting innovative services that respond to patients' needs and preferences, and allowing flexibility in evidence-based practice and the expansion of the behavioral health workforce. These proposals should help meet the health care needs of a growing racial/ethnic minority population. PMID- 27269015 TI - Quality Measures For Mental Health And Substance Use: Gaps, Opportunities, And Challenges. AB - Following up on its Crossing the Quality Chasm report, in 2006 the Institute of Medicine issued a report that included sweeping recommendations to improve the quality of behavioral health care in the United States. To date, few of those recommendations have been implemented, and there is little evidence that behavioral health care quality has improved significantly over the past ten years. However, the advent of health care reform, parity of insurance coverage, and growing recognition of the impact of behavioral health disorders on population health and health care costs have created new demands and opportunities for expanded and innovative strategies to assess the quality of care for this patient population. We provide an overview of the current state of quality measurement in behavioral health, identify key priorities for measure development, and describe the most important challenges. We recommend a coordinated plan that would boost investment in developing, evaluating, and implementing behavioral health quality measures; conduct research to develop the evidence necessary to support a more robust set of measures; overcome barriers to the improvement and linking of data sources; and expand efforts to build the capacity of the clinical workforce, in partnership with consumers, to improve quality. PMID- 27269016 TI - Federal Parity In The Evolving Mental Health And Addiction Care Landscape. AB - The intent of the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 is to eliminate differences between health insurance coverage of mental health and substance use disorder benefits and coverage of medical or surgical benefits. The Affordable Care Act significantly extended the reach of the Wellstone-Domenici law by applying it to new insurance markets. We summarize the evolution of legislative and regulatory actions to bring about federal insurance parity. We also summarize available evidence on how the Wellstone-Domenici law has contributed to addressing insurance discrimination; rectifying market inefficiencies due to adverse selection; and altering utilization, spending, and health outcomes for people with mental health and substance use disorders. In addition, we highlight important gaps in knowledge about how parity has been implemented, describe the groups still lacking parity level coverage, and make recommendations on steps to improve the likelihood that the Wellstone-Domenici law will fulfill the aims of its architects. PMID- 27269017 TI - Access To Mental Health Care Increased But Not For Substance Use, While Disparities Remain. AB - We assessed whether early implementation of Affordable Care Act (ACA) Medicaid expansion and state health insurance exchanges increased access to mental health and substance use treatment among those in need and whether these changes differed by racial/ethnic group. We found that mental health treatment rates increased significantly but found no evidence of a reduction in the wide racial/ethnic disparities in mental health treatment that preceded ACA expansion from 2005 to 2013. PMID- 27269018 TI - Risk-Adjustment Simulation: Plans May Have Incentives To Distort Mental Health And Substance Use Coverage. AB - Under the Affordable Care Act, the risk-adjustment program is designed to compensate health plans for enrolling people with poorer health status so that plans compete on cost and quality rather than the avoidance of high-cost individuals. This study examined health plan incentives to limit covered services for mental health and substance use disorders under the risk-adjustment system used in the health insurance Marketplaces. Through a simulation of the program on a population constructed to reflect Marketplace enrollees, we analyzed the cost consequences for plans enrolling people with mental health and substance use disorders. Our assessment points to systematic underpayment to plans for people with these diagnoses. We document how Marketplace risk adjustment does not remove incentives for plans to limit coverage for services associated with mental health and substance use disorders. Adding mental health and substance use diagnoses used in Medicare Part D risk adjustment is one potential policy step toward addressing this problem in the Marketplaces. PMID- 27269019 TI - Achieving Mental Health Care Parity Might Require Changes In Payments And Competition. AB - One of the most prominent features of the Affordable Care Act has been the promotion of individual health plans chosen by consumers in the Marketplaces. These plans are subject to regulation and paid by risk-adjusted capitation, a set of policies known as managed competition. Individual health insurance markets, however, are vulnerable to what economists describe as efficiency problems stemming from adverse selection, and Marketplaces are no exception. Health plans have incentives to discriminate against services used by people with certain chronic illnesses, including mental health conditions. Parity regulations, which dictate coverage for mental health benefits on par with medical and surgical benefits, can eliminate discrimination in coverage but redirect discrimination toward hard-to-regulate tactics from managed care such as restrictive network design and provider payment. This article reviews policy options to contend with ongoing selection issues. "Better enforcement" of parity has less chance of success than more fundamental but feasible changes in the way plans are paid or in the way competition among plans is structured. PMID- 27269020 TI - Decline In Public Substance Use Disorder Treatment Centers Most Serious In Counties With High Shares Of Black Residents. AB - Previous research has associated declines in health care resources such as hospitals and trauma centers with communities' racial composition. However, little is known about changes in the substance use disorder treatment infrastructure in recent years and the implications for black communities. We used data for the period 2002-10 from the National Survey of Substance Abuse Treatment Services to describe changes in the supply of public and private outpatient facilities for substance use disorder treatment, and to determine whether these trends had implications for the geographical availability of these facilities in counties with high percentages of black residents. During the study period the number of publicly owned facilities declined 17.2 percent, whereas the number of private for-profit facilities grew 19.1 percent. At baseline, counties with very high percentages of black residents (that is, more than one standard deviation above the mean) were more likely than counties with less than the mean percentage of black residents to be served by public facilities and were thus disproportionately affected by the overall decline in public facilities. Future research should examine the effect of expanding eligibility for Medicaid on the supply of substance use disorder treatment facilities across diverse communities. PMID- 27269022 TI - In Fighting An Opioid Epidemic, Medication-Assisted Treatment Is Effective But Underused. PMID- 27269021 TI - Prescription Drug Monitoring Programs Are Associated With Sustained Reductions In Opioid Prescribing By Physicians. AB - State prescription drug monitoring programs are promising tools to rein in the epidemic of prescription opioid overdose. We used data from a national survey to assess the effects of these programs on the prescribing of opioid analgesics and other pain medications in ambulatory care settings at the point of care in twenty four states from 2001 to 2010. We found that the implementation of a prescription drug monitoring program was associated with more than a 30 percent reduction in the rate of prescribing of Schedule II opioids. This reduction was seen immediately following the launch of the program and was maintained in the second and third years afterward. Effects on overall opioid prescribing and prescribing of non-opioid analgesics were limited. Increased use of these programs and the adoption of new policies and practices governing their use may have contributed to sustained effectiveness. Future studies are needed to evaluate the policies' comparative effectiveness. PMID- 27269023 TI - Justice-Involved Adults With Substance Use Disorders: Coverage Increased But Rates Of Treatment Did Not In 2014. AB - More than one-third of US adults in the criminal justice system have substance use disorders, which contribute to health problems and recidivism. Health insurance and criminal justice reforms initiated in the last decade offer opportunities for increasing treatment access among justice-involved individuals. Using national survey data, we examined trends in treatment of substance use disorders from 2004 to 2014 among adults who reported past-year criminal justice contact and met screening criteria for substance use disorders. We found that the uninsurance rate was relatively unchanged in that population from 2004 to 2013. In 2014, the first year of the Affordable Care Act Medicaid expansion, the uninsurance rate among justice-involved individuals with substance use disorders declined from 38 percent to 28 percent. Although overall treatment rates did not increase in 2014, individuals receiving treatment were more likely to have their care paid for by Medicaid than in the prior decade. Medicaid reimbursement can be a critical lever for improving the quality and continuity of substance use disorder treatment for justice-involved populations. PMID- 27269025 TI - Improving Access To Care And Reducing Involvement In The Criminal Justice System For People With Mental Illness. AB - People with mental illness make up a disproportionate share of the criminal justice-involved population. The passage of critical new reforms affecting health care for vulnerable populations under the Affordable Care Act and the Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 presents unique opportunities to transform systems of care and avert criminal justice involvement. In addition, state and local jurisdictions have implemented a number of strategies to divert people with mental illness from the criminal justice system and reduce recidivism. In this article we summarize current knowledge about the involvement of people with mental illness in the criminal justice system and consider the recent opportunities presented by national and local policies that aim to lower the proportion of such people who are incarcerated. PMID- 27269024 TI - Gun Violence, Mental Illness, And Laws That Prohibit Gun Possession: Evidence From Two Florida Counties. AB - Gun violence kills about ninety people every day in the United States, a toll measured in wasted and ruined lives and with an annual economic price tag exceeding $200 billion. Some policy makers suggest that reforming mental health care systems and improving point-of-purchase background checks to keep guns from mentally disturbed people will address the problem. Epidemiological research shows that serious mental illness contributes little to the risk of interpersonal violence but is a strong factor in suicide, which accounts for most firearm fatalities. Meanwhile, the effectiveness of gun restrictions focused on mental illness remains poorly understood. This article examines gun-related suicide and violent crime in people with serious mental illnesses, and whether legal restrictions on firearm sales to people with a history of mental health adjudication are effective in preventing gun violence. Among the study population in two large Florida counties, we found that 62 percent of violent gun crime arrests and 28 percent of gun suicides involved individuals not legally permitted to have a gun at the time. Suggested policy reforms include enacting risk-based gun removal laws and prohibiting guns from people involuntarily detained in short term psychiatric hospitalizations. PMID- 27269026 TI - Suicide Prevention: An Emerging Priority For Health Care. AB - Suicide is a significant public health problem. It is the tenth leading cause of death in the United States, and the rate has risen in recent years. Many suicide deaths are among people recently seen or currently under care in clinical settings, but suicide prevention has not been a core priority in health care. In recent years, new treatment and management strategies have been developed, tested, and implemented in some organizations, but they are not yet widely used. This article examines the feasibility of improving suicide prevention in health care settings. In particular, we consider Zero Suicide, a model for better identification and treatment of patients at risk for suicide. The approach incorporates new tools for screening, treatment, and support; it has been deployed with promising results in behavioral health programs and primary care settings. Broader adoption of improved suicide prevention care may be an effective strategy for reducing deaths by suicide. PMID- 27269027 TI - The Recovery Movement: Implications For Mental Health Care And Enabling People To Participate Fully In Life. AB - The recovery movement, which broadly recognizes the ability of people with mental illnesses to participate in the mainstream of society, stems from a confluence of factors, including longitudinal data showing that many people eventually recover from serious mental illness. Perhaps as important to the emergence and growth of the recovery movement has been the increasing role that people "in recovery" have played in advocating for person-centered care, greater self-determination for those with mental illnesses, and an enhanced focus on restoring functioning for individuals above and beyond symptom reduction. The Americans with Disabilities Act of 1990 redefined serious forms of mental illness as disabilities, which led to the development of a range of accommodations to enable people with psychiatric disabilities to live in their own homes, work, go to school, and perform other normative adult roles such as parent and parishioner even while suffering symptoms. The Affordable Care Act provides additional levers for expanding the use of peer health navigators and shifting care to a collaborative model in which people can play active roles in their own care. While stigma and discrimination continue to pose formidable obstacles, the foundations have been laid for mental health practice to come closer to resembling health care for other medical conditions. PMID- 27269028 TI - Individual Placement And Support Services Boost Employment For People With Serious Mental Illnesses, But Funding Is Lacking. AB - The majority of people with serious mental illnesses want to work. Individual placement and support services, an evidence-based supported employment intervention, enables about 60 percent of people with serious mental illnesses who receive the services to gain competitive employment and improve their lives, but the approach does not lead to fewer people on government-funded disability rolls. Yet individual placement and support employment services are still unavailable to a large majority of people with serious mental illnesses in the United States. Disability policies and lack of a simple funding mechanism remain the chief barriers. A recent federal emphasis on early-intervention programs may increase access to employment services for people with early psychosis, but whether these interventions will prevent disability over time is unknown. PMID- 27269029 TI - Behavioral Health Information Technology: From Chaos To Clarity. AB - The use of health information technology (IT) in general health care has been shown to have significant potential to facilitate the delivery of safe, high quality, and cost-effective care. However, its application to behavioral health care has been slow, limiting the extent to which consumers seeking care for mental health or substance use disorders can derive its benefits. The goal of this article is to provide an overview of the use of health IT in behavioral health and to describe some unique challenges experienced in that domain. We also highlight current obstacles to, and recommendations for, the use of health IT in improving the quality of behavioral health care. We conclude with recommendations for prioritizing the work that we believe will move the US health care system toward more effective, efficient, and patient-centric care in behavioral health. PMID- 27269030 TI - Global Burden Of Disease Studies: Implications For Mental And Substance Use Disorders. AB - Global Burden of Disease studies have highlighted mental and substance use disorders as the leading cause of disability globally. Using the studies' findings for policy and planning requires an understanding of how estimates are generated, the required epidemiological data are gathered, disability and premature mortality are defined and counted, and comparative risk assessment for risk-factor analysis is undertaken. The high burden of mental and substance use disorders has increased their priority on the global health agenda, but not enough to prompt concerted action by governments and international agencies. Using Global Burden of Disease estimates in health policy and planning requires combining them with other information such as evidence on the cost-effectiveness of interventions designed to reduce the disorders' burden. Concerted action is required by mental health advocates and policy makers to assemble this evidence, taking into account the health, social, and economic challenges facing each country. PMID- 27269032 TI - In Two Maine Towns, Schools Address The Mental Health Of Refugee Children. AB - School-based programs in Auburn and Lewiston help meet the unique health needs of refugees from war-torn Somalia. PMID- 27269031 TI - Trends In News Media Coverage Of Mental Illness In The United States: 1995-2014. AB - The United States is engaged in ongoing dialogue around mental illness. To assess trends in this national discourse, we studied the volume and content of a random sample of 400 news stories about mental illness from the period 1995-2014. Compared to news stories in the first decade of the study period, those in the second decade were more likely to mention mass shootings by people with mental illnesses. The most frequently mentioned topic across the study period was violence (55 percent overall) divided into categories of interpersonal violence or self-directed (suicide) violence, followed by stories about any type of treatment for mental illness (47 percent). Fewer news stories, only 14 percent, described successful treatment for or recovery from mental illness. The news media's continued emphasis on interpersonal violence is highly disproportionate to actual rates of violence among those with mental illnesses. Research suggests that this focus may exacerbate social stigma and decrease support for public policies that benefit people with mental illnesses. PMID- 27269033 TI - Foundation Funding For Behavioral Health Care. PMID- 27269035 TI - Working Together To Help People In China Breathe Better. PMID- 27269041 TI - Internal Consistency and Power When Comparing Total Scores from Two Groups. AB - Researchers now know that when theoretical reliability increases, power can increase, decrease, or stay the same. However, no analytic research has examined the relationship of power to the most commonly used type of reliability-internal consistency-and the most commonly used measures of internal consistency, coefficient alpha and ICC(A,k). We examine the relationship between the power of independent samples t tests and internal consistency. We explicate the mathematical model upon which researchers usually calculate internal consistency, one in which total scores are calculated as the sum of observed scores on K measures. Using this model, we derive a new formula for effect size to show that power and internal consistency are influenced by many of the same parameters but not always in the same direction. Changing an experiment in one way (e.g., lengthening the measure) is likely to influence multiple parameters simultaneously; thus, there are no simple relationships between such changes and internal consistency or power. If researchers revise measures to increase internal consistency, this might not increase power. To increase power, researchers should increase sample size, select measures that assess areas where group differences are largest, and use more powerful statistical procedures (e.g., ANCOVA). PMID- 27269042 TI - Interprofessional Education and Practice Guide No. 6: Developing practice-based interprofessional learning using a short placement model. AB - Offering undergraduate and post-qualified learners opportunities to take part in, and reflect on, the nature of interprofessional working when in practice remains an important goal for interprofessional educators. There are a plethora of opportunities within hospital and community care for learners to actively participate in health and social care delivery where collaborative practice prevails. However, it remains challenging to know how to establish and sustain meaningful interprofessional practice-based learning. This is because profession specific teaching is prioritised and many teams are under-resourced, leaving little time for additional teaching activities. In some instances, practitioners lack the knowledge concerning how to design meaningful interprofessional learning and often feel unprepared for this teaching because of limited interprofessional faculty development. Others are simply unaware of the presence of the different students within their practice area. This guide offers key lessons developed over many years for setting up practice-based interprofessional education. The learning model has been adapted and adopted in different settings and countries and offers a method for engaging clinical front-line practitioners in learning with, and from learners who can help support and in some instances advance care delivery. PMID- 27269043 TI - A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine. AB - AIM: The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP RA), for the acute treatment of migraine. METHODS: This double-blind, placebo controlled study randomized 834 participants to treat one migraine attack with ubrogepant 1 mg, 10 mg, 25 mg, 50 mg, 100 mg, or placebo in a 1:1 ratio. The co primary endpoints were pain freedom and headache response at two hours. The first primary hypothesis tested the dose-response trend for two-hour pain freedom using a logistic regression model. Subsequent hypotheses tested the effects of each dose on the co-primary endpoints, using a closed sequential testing procedure to control for multiplicity. RESULTS: A total of 527 participants received ubrogepant and 113 received placebo. A positive response trend in the proportion of participants achieving two-hour pain freedom was demonstrated (p < 0.001). Ubrogepant 100 mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response. Per the prespecified multiplicity strategy, this nonsignificant result precluded further formal hypothesis testing, although the 50 mg and 25 mg doses demonstrated nominal significance over placebo for two-hour pain freedom (unadjusted p < 0.05). Overall, adverse events were similar between ubrogepant and placebo. CONCLUSION: This trial supports ubrogepant's efficacy and provides further evidence that CGRP RAs are viable options for the acute treatment of migraine. PMID- 27269044 TI - COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients. AB - AIM: We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. PATIENTS & METHODS: We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. RESULTS: Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms. CONCLUSION: Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings. PMID- 27269045 TI - Corrigendum to "Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects" [J. Autoimmun. 47C (2013) 1-16]. PMID- 27269046 TI - Are good intentions putting the vaccination ecosystem at risk? AB - Vaccination is made possible by an interconnected and interdependent ecosystem of vaccine producers, vaccination policy makers and implementers, and vaccine procurers and funders. The future of vaccination depends on the continued health of this ecosystem and its ability to produce, purchase, deliver, and innovate. However, the number of vaccine producers that also do significant research and development has decreased over the last several years. Many of these R&D-based producers have been forced to cease production of critical vaccines, despite global shortages, so that in several cases only one or two producers remain. We discuss the reasons for these changes and what might be done to maintain a healthy vaccination ecosystem. PMID- 27269047 TI - Association of Combined Complement Factor H Y402H and ARMS/LOC387715 A69S Polymorphisms with Age-related Macular Degeneration: A Meta-analysis. AB - PURPOSE: Complement factor H (CFH) Y402H (rs1061170) and age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphisms shown to have significant association with age-related macular degeneration (AMD). In this meta analysis, we pooled the results of the available association studies between combined ARMS2/LOC387715A69S-CFHY402H genotypes and AMD to estimate the possible synergistic or multiplicative effects. METHODS: Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index. To modify the heterogeneity in the variables, we used random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects, we calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V). RESULTS: We included eight studies with 2915 AMD patients and 3505 control subjects. Considering the GGTT genotypes as reference lines, the pooled AMD Odds Ratios for stratified combined genotypes were 2.32 (95% CI 1.64-3.28) for GGnon TT, 2.49 (95% CI 1.72-3.60) for non-GGTT, and 7.82 (95% CI 5.09-12.00) for non GGnon-TT. Pooled synergy analysis revealed RERI = 4.08 (95% CI 3.15-5.27), AP = 0.50 (95% CI 0.42-0.57), S = 2.31 (95% CI 1.9-2.82), and V = 1.21 (95% CI 0.93 1.49). CONCLUSION: This analysis revealed the synergistic and positive multiplicative effect of these two genes indicating that there is a common pathway of ARMS2/LOC387715 and CFH in AMD pathogenesis which may be the complement system pathway. PMID- 27269048 TI - Topological semimetals predicted from first-principles calculations. AB - We have given a summary on our theoretical predictions of three kinds of topological semimetals (TSMs), namely, Dirac semimetal (DSM), Weyl semimetal (WSM) and node-line semimetal (NLSM). TSMs are new states of quantum matter, which are different from topological insulators. They are characterized by the topological stability of the Fermi surface, whether it encloses band crossing points, i.e. Dirac cone-like energy nodes, or not. They are distinguished from each other by the degeneracy and momentum space distribution of the nodal points. To realize these intriguing topological quantum states is quite challenging and crucial to both fundamental science and future application. Na3Bi and Cd3As2 were theoretically predicted to be DSM in 2012 and 2013 respectively. Their experimental verification in 2014 have ignited intensive studies on TSMs. The subsequent theoretical prediction of a nonmagnetic WSM in the TaAs family stimulated a second wave and many experimental works were released out in 2015. In 2014, a kind of three dimensional crystal of carbon was proposed to be an NLSM due to negligible spin-orbit coupling and coexistence of time-reversal and inversion symmetry. Though the final experimental confirmation of NLSM is still missing, there have been several theoretical proposals, including Cu3PdN from us. In the final part, we have summarized the whole family of TSMs and their relationships. PMID- 27269049 TI - Erratum to "Interleukin-10 deficiency aggravates angiotensin II-induced cardiac remodeling in mice"[Life Sci. 146 (2016) 214-221]. PMID- 27269050 TI - Agomelatine affects rat suprachiasmatic nucleus neurons via melatonin and serotonin receptors. AB - AIMS: The hypothalamic suprachiasmatic nucleus (SCN), which functions as a circadian pacemaker in mammals, is influenced by melatonin and serotonin. Agomelatine, which acts as an antidepressant and can synchronize disturbed circadian rhythms, displays a unique mechanism of action involving both melatonergic agonist and 5-HT2C antagonist properties. This study investigated the dose-dependent effects of agomelatine, melatonin and a selective 5-HT2C receptor antagonist, S32006, on SCN neurons in an in vitro slice preparation. MAIN METHODS: Brain slices containing the SCN were prepared from male Wistar rats and maintained in a recording chamber. Changes in firing rates of SCN neurons were recorded after perfusion of drugs. KEY FINDINGS: SCN firing rates were dose dependently suppressed by 19.2-80.9% following perfusion of 0.04-0.32mM agomelatine (p<0.001, IC50=0.14mM). Perfusion with melatonin (0.4-3.2mM) resulted in 16.6-62.5% dose-dependent reductions in firing rates (at least p<0.01, IC50=1.59mM) and of the duration of suppression. A selective melatonin receptor antagonist (S22153 at 0.32mM) and a 5-HT2c receptor agonist (Ro60-0175) reduced the suppressive effects of 0.16mM agomelatine by 35% and 50.2%, respectively. A 5 HT2C receptor antagonist (S32006; 0.03-0.12mM) significantly decreased SCN firing rates (19.6-91.8%; at least p<0.05, IC50=0.05mM). Co-perfusion of S32006 (0.06mM) with a 5-HT2C agonist (Ro60-0175; 0.003mM) reduced suppressions evoked by S32006 alone by ~72.1%. SIGNIFICANCE: These results are consistent with the hypothesis that agomelatine acts directly on the SCN via both agonist effects at melatonergic receptors and antagonist effects at 5-HT2C receptors, which parallel its mechanisms of action as an antidepressant. PMID- 27269051 TI - Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function. AB - Cochlear hair cells convert sound-induced vibration into electrical signals. FAM65B mutations cause hearing loss by an unknown mechanism. Using biochemistry and stochastic optical reconstruction microscopy (STORM), we show here that Fam65b oligomers form a circumferential ring near the basal taper of the mechanically sensitive stereocilia of murine hair cells. Taperin, a second protein near the taper, forms a dense-core-like structure that is disrupted in the absence of Fam65b. Stereocilia of Fam65b-deficient murine hair cells start to develop, but mechanotransduction is affected and stereocilia deteriorate. Yeast two-hybrid screens identify RhoC as a Fam65b binding partner. RhoC co-localizes with Fam65b in stereocilia and regulates Fam65b oligomerization. Binding to RhoC and oligomerization are critical for Fam65b function. Our findings thus reveal a highly organized compartment near the base of stereocilia that is critical for hair cell function and affected in disease. PMID- 27269052 TI - Survey of undeclared egg allergen levels in the most frequently recalled food types (including products bearing precautionary labelling). AB - Since the number of recalls involving undeclared allergens is commonly associated with bakery and snack foods, we aimed to determine the frequency of egg allergens in a large number of these products using two commercial enzyme-linked immunosorbent assay (ELISA) methods. Samples were chosen that either had no egg identified on the product label or which had an egg precautionary statement. Among all samples, egg protein was detected in 5% of products using a Morinaga (MO) kit and 1% of products using a R-Biopharm (RB) kit. For bakery samples, egg protein was detected in 6% of 363 samples with no precautionary labelling (6% by MO and 1% by RB kit) and 12% of 80 samples which had precautionary labelling. For snack samples, egg protein was detected in 2% of 371 samples with no precautionary labelling (2% by MO and < 1% by RB kit) and 5% of 21 samples which had precautionary labelling. The disagreement rates between two methods were 5.2% for bakery products and 2.6% for snack products. The sample repeatability was at an acceptable level for bakery (< 12.5%) and snack foods (< 7.5%) for each method. The relative standard deviation between test kits was high (103.1%) for bakery foods. Four bakery products without precautionary labelling had a higher level of egg protein per serving compared with the eliciting dose (ED10 of 3.7 mg protein) for egg allergic patients. These results highlight the fact that detection methodology plays a vital role for accurate labelling control and mitigation of risk for egg allergic consumers. PMID- 27269053 TI - Electro-hyperthermia up-regulates tumour suppressor Septin 4 to induce apoptotic cell death in hepatocellular carcinoma. AB - PURPOSE: Modulated electro-hyperthermia (mEHT) has been shown to be effective against various types of human tumours, including hepatocellular carcinoma (HCC). Here we aimed to investigate the molecular mechanism underlying the cytotoxic effects of mEHT to HCC cells. MATERIALS AND METHODS: Human liver cancer cell lines, Huh7 and HepG2, were treated with mEHT (42 degrees C/60 min) three times at 2-day intervals. Growth inhibition and apoptotic induction were evaluated using MTS, microscopic analysis, a clonogenic assay, annexin V/PI staining and a ccK18 ELISA. Global changes in gene expression were examined using RNA sequencing to obtain insights into molecular changes in response to mEHT. For in vivo evaluation of mEHT we used HepG2 HCC xenografts grown in nude mice. RESULTS: mEHT suppressed HCC cell proliferation and long-term colony formation through induction of apoptosis. The growth inhibitory effects are induced through a subset of molecular changes. Notably the expression level of septin 4 (SEPT4) (involved in pro-apoptotic activity and growth suppression) was up-regulated, whereas a key regulator of invasiveness G-Protein coupled receptor 64 (GPR64) was repressed. Subsequent Western blotting confirmed that the common increase in tumour suppressor SEPT4 in both Huh7 and HepG2 cells is accompanied by the restoration of cyclin-dependent kinase (CDK) inhibitor p21 and decrease in pro caspase 7 and pro-caspase 3, thereby accelerating apoptotic signalling in HCC cells. Additionally, mEHT significantly inhibited the growth of human HCC xenografts in nude mice. CONCLUSIONS: These findings suggest that apoptotic cell death induced by mEHT is mediated by the up-regulation of tumour suppressor SEPT4 in human HCC cells. PMID- 27269054 TI - Effect of booster doses of poliovirus vaccine in previously vaccinated children, Clinical Trial Results 2013. AB - BACKGROUND: Considering the current polio situation Pakistan needs vaccine combinations to reach maximum population level immunity. The trial assessed whether inactivated poliovirus vaccine (IPV) can be used to rapidly boost immunity among children in Pakistan. METHODS: A five-arm randomized clinical trial was conducted among children (6-24months, 5-6years and 10-11years). Children were randomized in four intervention arms as per the vaccines they received (bOPV, IPV, bOPV+vitamin A, and bOPV+IPV) and a control arm which did not receive any vaccine. Baseline seroprevalence of poliovirus antibodies and serological immune response 28days after intervention were assessed. RESULTS: The baseline seroprevalence was high for all serotypes and the three age groups [PV1: 97%, 100%, 96%, PV2: 86%, 100%, 99%, PV3: 83%, 95%, 87% for the three age groups respectively]. There was significantly higher rate of immune response observed in the study arms which included IPV (95-99%) compared with bOPV only arms (11-43%), [p<0.001]; Vitamin A was not associated with improved immune response. Immune response rates in the IPV only arm and IPV+bOPV arm were similar [p>0.5]. CONCLUSION: IPV has shown the ability to efficiently close existing immunity gaps in a vulnerable population of children in rural Pakistan. PMID- 27269055 TI - Influential factors inducing suboptimal humoral response to vector-based influenza immunisation in Thoroughbred foals. AB - CONTEXT: Numerous equine influenza (EI) epizooties are reported worldwide. EI vaccination is the most efficient methods of prevention. However, not all horses develop protective immunity after immunisation, increasing the risk of infection and transmission. OBJECTIVES: This field study aimed to understand the poor response to primary EI vaccination. STUDY DESIGN: The EI antibody response was measured in 174 Thoroughbred foals set in 3 stud farms (SF#1 to SF#3) over a 2years period. All foals were immunised with a commercial recombinant canarypox based EI vaccine. Sera were tested by single radial haemolysis against the A/equine/Jouars/4/06 EIV strain (H3N8) at the time of the first vaccination (V1), 2weeks and 3months after the second immunisation (V2), 2days and 3months after the third immunisation (V3). RESULTS: The frequency of poor-responders (no detectable antibody titres) was surprisingly elevated after V2 (56.8%), increased to 81.7% at V2+3months and reached 98.6% at V3. The frequency of poor-responder was still 19.2%, 3months after V3. Two independent influential factors were identified. The short (V2+2weeks) and mid-term (V2+3months, V3+3months) antibody levels were positively correlated to the age at V1 (p-value=0.003, 0.031 and 0.0038, respectively). Presence of maternally-derived antibodies (MDA) at V1 was negatively correlated with antibody levels after V3 only (p-value=0.0056). Given that SF#1 antibody response was below clinical protective levels at all-time points studied, the annual boost immunisation (V4) was brought forward by 7.0+/ 1.1months. V1 was delayed by 7weeks the following year, which significantly increased short- and mid-term antibody titres (p-value=9.9e-07 and 2.31e-07, respectively). CONCLUSION: The age and MDA at first immunisation with the canarypox-based IE vaccine play an independent role in the establishment of antibody levels. This study also highlights the benefit provided by serological surveillance to evaluate herd immunity and to implement corrective management/vaccination measures. PMID- 27269056 TI - Assessment of safety and reproductive performance after vaccination with a modified live-virus PRRS genotype 1 vaccine in pregnant sows at various stages of gestation. AB - The objective of the present study was to assess safety and efficacy of a new modified live-virus porcine reproductive and respiratory syndrome (PRRS) genotype 1 vaccine in pregnant sows at various stages of gestation under field conditions. A total of 505 sows and gilts were allocated to two treatment groups and maintained in separate facilities. Animals of group 1 were vaccinated with a commercial modified live genotype 1 PRRSV vaccine (control product, CP), while animals of group 2 were immunized with a new modified live genotype 1 PRRSV vaccine (investigational veterinary product, IVP) (ReproCyc(r) PRRS EU, Boehringer Ingelheim Vetmedica GmbH). Injection site reactions were noted to be significantly less frequent in the IVP group compared to the CP group for pain (p=0.039), redness (p=0.030), heat (p=0.016) and swelling (p=0.002). The mean total number of piglets alive at weaning did not differ significantly between both study groups (10.6 vs. 11.0, p=0.375). However, pre-weaning mortality was significantly higher (p=0.005) in piglets from the CP group (14.1% vs. 10.9%). Analyses of reproductive performance data for both groups did not result in statistically significant differences between CP group and IVP group for number of piglets alive (12.7 and 12.6, respectively), healthy live (11.9 and 11.8), weak (0.7 and 0.5), stillborn (1.0 and 0.8) and mummified piglets (0.3 and 0.2) per litter. No differences were detected between both groups for piglet birth weights, while body weights at weaning (7.2kg vs. 6.6kg, p=0.026) and average daily gain (0.2445kg vs. 0.2211kg, p=0.037) were significantly higher in piglets from the IVP group. In conclusion, the administration of a single dose of ReproCyc(r) PRRS EU to sows and gilts at various stages of gestation confirmed non-inferiority to a commercial PRRS vaccine regarding safety and efficacy parameters under field conditions. PMID- 27269057 TI - Improving the immunogenicity of a trivalent Neisseria meningitidis native outer membrane vesicle vaccine by genetic modification. AB - Trivalent native outer membrane vesicles (nOMVs) derived from three genetically modified Neisseria meningitidis serogroup B strains have been previously evaluated immunologically in mice and rabbits. This nOMV vaccine elicited serum bactericidal activity (SBA) against multiple N. meningitidis serogroup B strains as well as strains from serogroups C, Y, W, and X. In this study, we used trivalent nOMVs isolated from the same vaccine strains and evaluated their immunogenicity in an infant Rhesus macaque (IRM) model whose immune responses to the vaccine are likely to be more predictive of the responses in human infants. IRMs were immunized with trivalent nOMV vaccines and sera were evaluated for exogenous human serum complement-dependent SBA (hSBA). Antibody responses to selected hSBA generating antigens contained within the trivalent nOMVs were also measured and we found that antibody titers against factor H binding protein variant 2 (fHbpv2) were very low in the sera from animals immunized with these original nOMV vaccines. To increase the fHbp content in the nOMVs, the vaccine strains were further genetically altered by addition of another fHbp gene copy into the porB locus. Trivalent nOMVs from the three new vaccine strains had higher fHbp antigen levels and generated higher anti-fHbp antibody responses in immunized mice and IRMs. As expected, fHbp insertion into the porB locus resulted in no PorB expression. Interestingly, higher expression of PorA, an hSBA generating antigen, was observed for all three modified vaccine strains. Compared to the trivalent nOMVs from the original strains, higher PorA levels in the improved nOMVs resulted in higher anti-PorA antibody responses in mice and IRMs. In addition, hSBA titers against other strains with PorA as the only hSBA antigen in common with the vaccine strains also increased. PMID- 27269058 TI - Evaluation of different heterologous prime-boost immunization strategies against Babesia bovis using viral vectored and protein-adjuvant vaccines based on a chimeric multi-antigen. AB - Protection against the intraerythrocytic bovine parasite Babesia bovis requires both humoral and cellular immune responses. Therefore, tailored combinations of immunogens targeted at both arms of the immune system are strategies of choice to pursue sterilizing immunity. In this study, different heterologous prime-boost vaccination schemes were evaluated in mice to compare the immunogenicity induced by a recombinant adenovirus, a modified vaccinia Ankara vector or a subunit vaccine all expressing a chimeric multi-antigen. This multi-antigen includes the immunodominant B and T cell epitopes of three B. bovis proteins: Merozoite Surface Antigen - 2c (MSA-2c), Rhoptry Associated Protein - 1 (RAP-1) and Heat Shock Protein 20 (HSP20). Both priming with the adenovirus or recombinant multi antigen and boosting with the modified vaccinia Ankara vector achieved a high degree of activation of TNFalpha and IFNgamma-secreting CD4(+) and CD8(+) specific T cells 60days after the first immunization. High titers of specific IgG antibodies were also detected at the same time point and lasted up to day 120 of the first immunization. Only the adenovirus - MVA combination triggered a marked isotype skew for the IgG2a antibody subclass meanwhile for the other immune traits analyzed here, both vaccination schemes showed similar performances. The immunological characterization in the murine model of these rationally designed immunogens led us to propose that adenoviruses as well as the bacterially expressed multi-antigen are highly reliable primer candidates to be considered in future experiments in cattle to test protection against bovine babesiosis. PMID- 27269059 TI - The impact of a pneumococcal conjugate vaccination program on the nasopharyngeal carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae among healthy children in Turkey. AB - BACKGROUND: The 7-valent conjugate pneumococcal vaccine (PCV7) was introduced by the Turkey National Immunization Program in 2008 and replaced by the PCV13 in 2011. We assessed the impact of PCV vaccination on the nasopharyngeal (NP) carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae (SP) among healthy Turkish children. METHODS: A prospective surveillance study was performed between September 2011 and September 2013 in Istanbul, Turkey. NP swabs, demographic data, and vaccination statuses were obtained from 2165 healthy children aged 0-18years. Pneumococcal carriage was defined by a positive culture; serotyping was performed via multiplex conventional PCR, and the antibiotic susceptibilities of the isolates were determined based on the minimum inhibitory concentration (MIC) values of the Clinical Laboratory Standards Institute (CLSI). RESULTS: The prevalence of pneumococcal carriage was 6.4%. The carriage rates were 8%, 7%, and 5% in the following age groups: 0-24months, 25-60months, and >60months, respectively. The carriage rate was significantly higher in the 0-24month age group than in the >60months age group (p=0.03). Sixty percent of the children were not vaccinated with any PCV; 4%, 2%, and 4% received at least 1, 2 or 3 doses and 30% children received the full schedule (4 doses) of either PCV7 or PCV13. Among the isolated S. pneumoniae strains, 45% were of the non-vaccine type (NVT) and 55% were of the vaccine type (VT). The children who received at least a single PCV dose had significantly lower odds of colonization via VT serotypes than the non-vaccinated children [odds ratio: 0.61 (95% confidence interval=0.41-0.91), p=0.01]. The percentages of the serotypes covered by PCV7 and PCV13 were 51% and 56%, respectively. The most frequently isolated serotypes were 6A/B/C (n=22, 16.5%), 19F (n=18, 13.5%), 23F (n=15, 11.2%), serotype 9V/A (n=10, 7.5%), 12F (n=5, 4.5%), 15A/F (n=7, 4.5%) and 22 A/F (n=6, 4.5%). Using the meningitis criteria and the MIC, 62% of the isolates were resistant to penicillin and 13% were non sensitive to ceftriaxone. Erythromycin and clindamycin resistance were 43% and 31%, respectively. CONCLUSION: We shown that following nation-wide PCV vaccination, S. pneumoniae NP carriage was decreased. PMID- 27269060 TI - The effect of mass vaccination campaigns against polio on the utilization of routine immunization services: A regression discontinuity design. AB - BACKGROUND: In most low and middle-income countries (LMIC), vaccines are primarily distributed by routine immunization services (RI) at health facilities. Additional opportunities for vaccination are also provided through mass vaccination campaigns, conducted periodically as part of disease-specific initiatives. It is unclear whether these campaigns are detrimental to RI services, or wether they may stimulate the utilization of RI. METHODS: Unobserved confounders and reverse causality have limited existing evaluations of the effects of mass vaccination campaigns on RI services. We explored the use of a regression discontinuity design (RDD) to measure these effects more precisely. This is a quasi-experimental method, which exploits random variations in birth dates to identify the causal effects of vaccination campaigns. We applied RDD to survey data on a nationwide vaccination campaign against Polio conducted in Bangladesh. RESULTS: We compared systematically the children born immediately before vs. after the vaccination campaign. These two groups had similar background characteristics, but differed by their exposure to the vaccination campaign. Contrary to previous studies, exposure to the campaign had positive effects on RI utilization. Children exposed to the campaign received between 0.296 and 0.469 additional doses of DPT vaccine by age 4months than unexposed children. CONCLUSIONS: RDD constitutes a promising tool to assess the effects of mass vaccination campaigns on RI services. It could be tested in additional settings, using larger and more precise datasets. It could also be extended to measure the effects of other disease-specific interventions on the functioning of health systems, in particular those that occur at a discrete point in time and/or include age-related eligibility criteria. PMID- 27269061 TI - Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity. AB - mRNA represents a new platform for the development of therapeutic and prophylactic vaccines with high flexibility with respect to production and application. We have previously shown that our two component self-adjuvanted mRNA based vaccines (termed RNActive(r) vaccines) induce balanced immune responses comprising both humoral and cellular effector as well as memory responses. Here, we evaluated the early events upon intradermal application to gain more detailed insights into the underlying mode of action of our mRNA-based vaccine. We showed that the vaccine is taken up in the skin by both non-leukocytic and leukocytic cells, the latter being mostly represented by antigen presenting cells (APCs). mRNA was then transported to the draining lymph nodes (dLNs) by migratory dendritic cells. Moreover, the encoded protein was expressed and efficiently presented by APCs within the dLNs as shown by T cell proliferation and immune cell activation, followed by the induction of the adaptive immunity. Importantly, the immunostimulation was limited to the injection site and lymphoid organs as no proinflammatory cytokines were detected in the sera of the immunized mice indicating a favorable safety profile of the mRNA-based vaccines. Notably, a substantial boostability of the immune responses was observed, indicating that mRNA can be used effectively in repetitive immunization schedules. The evaluation of the immunostimulation following prime and boost vaccination revealed no signs of exhaustion as demonstrated by comparable levels of cytokine production at the injection site and immune cell activation within dLNs. In summary, our data provide mechanistic insight into the mode of action and a rational for the use of mRNA-based vaccines as a promising immunization platform. PMID- 27269062 TI - Fred Chang: The shape of things to come. PMID- 27269063 TI - Tapping out a mechanical code for T cell triggering. AB - Mechanical forces play increasingly recognized roles in T cell receptor (TCR) signal transduction. Hu and Butte (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201511053) demonstrate that actin is required for T cells to generate forces at the TCR and that exogenous application of force can emulate these cytoskeletal forces and trigger T cell activation. PMID- 27269064 TI - How inhibitory cues can both constrain and promote cell migration. AB - Collective cell migration is a common feature in both embryogenesis and metastasis. By coupling studies of neural crest migration in vivo and in vitro with mathematical modeling, Szabo et al. (2016, J. Cell Biol., http://dx.doi.org/10.1083/jcb.201602083) demonstrate that the proteoglycan versican forms a physical boundary that constrains neural crest cells to discrete streams, in turn facilitating their migration. PMID- 27269066 TI - CFD modeling of the underwash effect of military helmets as a possible mechanism for blast-induced traumatic brain injury. AB - Underwash occurs as the incoming shockwaves enter the helmet subspace and develop a high pressure region at the opposite side of the head. The mechanism leading to the underwash is yet not well understood. To investigate this effect, the turbulent, supersonic flow of compressible air approaching the head-helmet assembly from different directions was studied through computational fluid dynamics simulations. The effects of different incident overpressures and helmet gap size on the underwash incidence were further evaluated. The backflow-induced pressure from the air traveling outside of the helmet on the outflow from the helmet, as well as the momentum change in the backside curve of the helmet were postulated as the main reasons for this effect. Side shockwaves predicted the highest underwash overpressures. The increase rate of the underwash reduced with increasing the incident shockwave intensity. PMID- 27269065 TI - Roles of paxillin family members in adhesion and ECM degradation coupling at invadosomes. AB - Invadosomes are acto-adhesive structures able to both bind the extracellular matrix (ECM) and digest it. Paxillin family members-paxillin, Hic-5, and leupaxin are implicated in mechanosensing and turnover of adhesion sites, but the contribution of each paxillin family protein to invadosome activities is unclear. We use genetic approaches to show that paxillin and Hic-5 have both redundant and distinctive functions in invadosome formation. The essential function of paxillin like activity is based on the coordinated activity of LD motifs and LIM domains, which support invadosome assembly and morphology, respectively. However, paxillin preferentially regulates invadosome assembly, whereas Hic-5 regulates the coupling between ECM degradation and acto-adhesive functions. Mass spectrometry analysis revealed new partners that are important for paxillin and Hic-5 specificities: paxillin regulates the acto-adhesive machinery through janus kinase 1 (JAK1), whereas Hic-5 controls ECM degradation via IQGAP1. Integrating the redundancy and specificities of paxillin and Hic-5 in a functional complex provides insights into the coupling between the acto-adhesive and ECM-degradative machineries in invadosomes. PMID- 27269120 TI - Zinc-Mediated C-3 alpha-Prenylation of Isatins with Prenyl Bromide: Access to 3 Prenyl-3-hydroxy-2-oxindoles and Its Application. AB - A convenient and highly alpha-regioselective strategy for the synthesis of 3 prenyl-3-hydroxy-2-oxindoles has been developed starting from isatins and prenylzinc with good to excellent yields. This protocol provides a straightforward and practical way to introduce an alpha-prenyl moiety into the C 3 position of isatins. The advantages of this reaction are use of the cheap and readily available reagents, operational simplicity, and wide substrate scope. Furthermore, this transformation was applied to the synthesis of several oxindole containing natural products, which further demonstrated the synthetic utility of this methodology. PMID- 27269119 TI - Discriminating Self and Non-Self by RNA: Roles for RNA Structure, Misfolding, and Modification in Regulating the Innate Immune Sensor PKR. AB - Pathogens are recognized by the innate immune system in part via their unique and complex RNA signatures. A key sensor in human innate immunity is the RNA activated protein kinase, protein kinase R (PKR), which has two double-stranded RNA (dsRNA) binding motifs (dsRBMs) at its N-terminus. Early studies described PKR as being activated potently by long stretches of perfect dsRNA, a signature typical of viruses. More recently, we and others have found that PKR is also activated by RNAs having structural defects such as bulges and internal loops. This Account describes advances in our understanding of the ability of PKR to detect diverse foreign RNAs and how that recognition plays significant roles in discriminating self from non-self. The experiments discussed employ a wide range of techniques including activation assays, native polyacrylamide gel electrophoresis (PAGE), protein footprinting, and small-angle X-ray scattering (SAXS). We discuss how misfolding and dimerization of RNA lead to activation of PKR. We also present recent findings on the activation of PKR by varied bacterial functional RNAs including ribozymes and riboswitches, which are among the few structured RNAs known to interact with PKR in a site-specific manner. Molecular models for how these structured RNAs activate PKR are provided. Studies by SAXS revealed that PKR straightens bent RNAs. Most external and internal RNA cellular modifications introduced in vitro and found naturally, such as the m7G cap and m6A group, abrogate activation of PKR, but other modifications, such as 5'-ppp and 2'-fluoro groups, are immunostimulatory and potential anticancer agents. Genome-wide studies of RNA folding in vitro and in vivo have provided fresh insights into general differences in RNA structure among bacteria, viruses, and human. These studies suggest that in vivo, cellular human RNAs are less folded than once thought, unwound by helicases, destabilized by m6A modifications, and often bound up with proteins, all conditions known to abrogate activation of PKR. It thus appears that non-self RNAs are detected as unmodified, naked RNAs with appreciable secondary and tertiary structure. Observation that PKR is activated by structured but otherwise diverse RNAs is consistent both with the broad spectrum nature of innate immunity and the nonspecific recognition of RNA by the dsRBM family. These findings provide a possible explanation for the apparent absence of protein-free structured human RNAs, such as ribozymes and riboswitches. PMID- 27269121 TI - The Interaction of Same-Sex Marriage Access With Sexual Minority Identity on Mental Health and Subjective Wellbeing. AB - Previous psychological and public health research has highlighted the impact of legal recognition of same-sex relationships on individual identity and mental health. Using a sample of U.S. sexual minority (N = 313) and heterosexual (N = 214) adults, participants completed a battery of mental health inventories prior to the nationwide legalization of same-sex marriage. Analyses of covariance (ANCOVAs) examining identity revealed sexual minority participants living in states where same-sex marriage was banned experienced significantly higher levels of internalized homonegativity than sexual minority participants living in states where same-sex marriage was legal, even after controlling for state-level political climate. Mental health ANCOVAs revealed sexual minority participants residing in states without same-sex marriage experienced greater anxiety and lower subjective wellbeing compared to sexual minority participants residing in states with same-sex marriage and heterosexual participants residing in states with or without same-sex marriage. Implications for public policy and future research directions are discussed. PMID- 27269122 TI - Serum and erythrocyte folate status of New Zealand women of childbearing age following a countrywide voluntary programme by the baking industry to fortify bread with folic acid. AB - OBJECTIVE: To estimate the folate status of New Zealand women of childbearing age following the introduction, in 2010, of a new voluntary folic acid fortification of bread programme. DESIGN: The 2011 Folate and Women's Health Survey was a cross sectional survey of women aged 18-44 years carried out in 2011. The survey used a stratified random sampling technique with the Electoral Roll as the sampling frame. Women were asked about consumption of folic-acid-fortified breads and breakfast cereals in a telephone interview. During a clinic visit, blood was collected for serum and erythrocyte folate measurement by microbiological assay. SETTING: A North Island (Wellington) and South Island (Dunedin) city centre in New Zealand. SUBJECTS: Two hundred and eighty-eight women, of whom 278 completed a clinic visit. RESULTS: Geometric mean serum and erythrocyte folate concentrations were 30 nmol/l and 996 nmol/l, respectively. Folate status was 30 40 % higher compared with women of childbearing age sampled as part of a national survey in 2008/09, prior to the introduction of the voluntary folic acid bread fortification programme. In the 2011 Folate and Women's Health Survey, reported consumption of fortified bread and fortified breakfast cereal in the past week was associated with 25 % (P=0.01) and 15 % (P=0.04) higher serum folate concentrations, respectively. CONCLUSIONS: Serum and erythrocyte folate concentrations have increased in New Zealand women of childbearing age since the number of folic-acid-fortified breads was increased voluntarily in 2010. Consumption of fortified breads and breakfast cereals was associated with a higher folate status. PMID- 27269124 TI - Directing Soft Matter in Water Using Electric Fields. AB - Directing the spatial organization of functional supramolecular and polymeric materials at larger length scales is essential for many biological and molecular optoelectronic applications. Although the application of electrical fields is one of the most powerful approaches to induce spatial control, it is rarely applied experimentally in aqueous solutions, since the low susceptibility of soft and biological materials requires the use of high fields, which leads to parasitic heating and electrochemical degradation. In this work, we demonstrate that we can apply electric fields when we use a mineral liquid crystal as a responsive template. Besides aligning and positioning functional soft matter, we show that the concentration of the liquid crystal template controls the morphology of the assembly. As our setup is very easy to operate and our approach lacks specific molecular interactions, we believe it will be applicable for a wide range of (aqueous) materials. PMID- 27269123 TI - Latent-variable modeling of brain gray-matter volume and psychopathy in incarcerated offenders. AB - Advanced statistical modeling has become a prominent feature in psychological science and can be a useful approach for representing the neural architecture linked to psychopathology. Psychopathy, a disorder characterized by dysfunction in interpersonal-affective and impulsive-antisocial domains, is associated with widespread neural abnormalities. Several imaging studies suggest that underlying structural deficits in paralimbic regions are associated with psychopathy. Although these studies are useful, they make assumptions about the organization of the brain and its relevance to individuals displaying psychopathic features. Capitalizing on statistical modeling, in the present study (N = 254), we used latent-variable methods to examine the structure of gray-matter volume in male offenders, and assessed the latent relations between psychopathy and gray-matter factors reflecting paralimbic and nonparalimbic regions. Results revealed good fit for a 4-factor gray-matter paralimbic model and these first-order factors were accounted for by a superordinate paralimbic "system" factor. Moreover, a superordinate psychopathy factor significantly predicted the paralimbic, but not the nonparalimbic factor. The latent-variable paralimbic model, specifically linked with psychopathy, goes beyond understanding single brain regions within the system and provides evidence for psychopathy-related gray-matter volume reductions in the paralimbic system as a whole. (PsycINFO Database Record PMID- 27269125 TI - Influence of Different Defects in Vertically Aligned Carbon Nanotubes on TiO2 Nanoparticle Formation through Atomic Layer Deposition. AB - The chemical inertness of carbon nanotubes (CNT) requires some degree of "defect engineering" for controlled deposition of metal oxides through atomic layer deposition (ALD). The type, quantity, and distribution of such defects rules the deposition rate and defines the growth behavior. In this work, we employed ALD to grow titanium oxide (TiO2) on vertically aligned carbon nanotubes (VACNT). The effects of nitrogen doping and oxygen plasma pretreatment of the CNT on the morphology and total amount of TiO2 were systematically studied using transmission electron microscopy, Raman spectroscopy, and thermogravimetric analysis. The induced chemical changes for each functionalization route were identified by X-ray photoelectron and Raman spectroscopies. The TiO2 mass fraction deposited with the same number of cycles for the pristine CNT, nitrogen doped CNT, and plasma-treated CNT were 8, 47, and 80%, respectively. We demonstrate that TiO2 nucleation is dependent mainly on surface incorporation of heteroatoms and their distribution rather than structural defects that govern the growth behavior. Therefore, selecting the best way to functionalize CNT will allow us to tailor TiO2 distribution and hence fabricate complex heterostructures. PMID- 27269126 TI - Incorporating measurable ('minimal') residual disease-directed treatment strategies to optimize outcomes in adults with acute myeloid leukemia. AB - Curative-intent therapy leads to complete remissions in many adults with acute myeloid leukemia (AML), but relapse remains common. Numerous studies have unequivocally demonstrated that the persistence of measurable ('minimal') residual disease (MRD) at the submicroscopic level during morphologic remission identifies patients at high risk of disease recurrence and short survival. This association has provided the impetus to customize anti-leukemia therapy based on MRD data, a strategy that is now routinely pursued in acute promyelocytic leukemia (APL). While it is currently uncertain whether this approach will improve outcomes in AML other than APL, randomized studies have validated MRD based risk-stratified treatment algorithms in acute lymphoblastic leukemia. Here, we review the available studies examining MRD-directed therapy in AML, appraise their strengths and limitations, and discuss avenues for future investigation. PMID- 27269127 TI - Time-Resolved Magneto-Optical Kerr Effect of Magnetic Thin Films for Ultrafast Thermal Characterization. AB - Thermomagnetic and magneto-optical effects are two fundamental but unique phenomena existing in magnetic materials. In this work, we demonstrate ultrafast time-resolved magneto-optical Kerr effect (TR-MOKE) as an advanced thermal characterization technique by studying the original factors of the MOKE signal from four magnetic transducers, including TbFe, GdFeCo, Co/Pd, and CoFe/Pt. A figure of merit is proposed to evaluate the performance of the transducer layers, corresponding to the degree of the signal-to-noise ratio in TR-MOKE measurements. We observe improved figure of merit for rare-earth transition-metal-based TbFe and GdFeCo transducers and attribute this improvement to their relatively larger temperature-dependent magnetization and the Kerr rotation angle at the saturated magnetization state. Furthermore, an optimal thickness of TbFe is found to be ~18.5 nm to give the best performance. Our findings will facilitate the nanoscale thermal characterization and the device design where the thermo-magneto-optical coupling plays an important role. PMID- 27269128 TI - Synovial sarcoma of the hypopharynx - a case report and literature review. PMID- 27269129 TI - Transoral robotic supraglottic partial laryngectomy: report of the first Brazilian case. PMID- 27269130 TI - New York University medical cadavers found in mass grave. PMID- 27269131 TI - Kaushik Ramaiya: a doctor who makes more than a difference. PMID- 27269132 TI - A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming. AB - Telomere length (TL) has been studied extensively in adults; however, limited information exists regarding maternal influences on TL in utero. The objective of this study was to investigate the relationship between fetal red blood cell (RBC) folate levels, a surrogate measure for maternal folate levels, and TL. We hypothesized that umbilical cord RBC folate concentrations would positively correlate with fetal TL. Data for this analysis were collected as part of a prospective cohort study that recruited pregnant women upon admission into labor and delivery. Cord blood was collected for 96 maternal-fetal dyads, and DNA analysis was performed using quantitative polymerase chain reaction. The telomere to single copy gene ratio method was used to determine TL, and RBC folate levels were measured. Statistical analysis was conducted by incorporating a bootstrapping approach into generalized linear modeling-based analyses. Consistent significant positive correlations were observed between RBC folate and TL (telomere to single copy gene ratio) with 9880 of the 10000 (98.8%) iterations performed having a P value less than .05. Our study shows a positive association between umbilical cord RBC folate and fetal TL at birth. These findings may provide a pathway of understanding and preventing adult-onset disease and mortality through intrauterine reprogramming. PMID- 27269133 TI - Prognostic value of posttreatment neutrophil-lymphocyte ratio in head and neck squamous cell carcinoma treated by chemoradiotherapy. AB - OBJECTIVE: An inflammatory-immunological marker, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), was evaluated as a predictive marker of advanced head and neck cancer patients receiving chemoradiotherapy. METHODS: This study included 104 patients with treatment-naive head and neck cancer who underwent definitive chemoradiotherapy. An inflammatory marker was measured at baseline and after 1 month of treatment. Univariate and multivariate analyses using Cox proportional hazards model were used to identify predictors of progression-free survival (PFS) and overall survival (OS). RESULTS: A univariate analysis revealed that T,N-stage, the pre- and posttreatment NLRs were significant predictors of progression after the chemoradiotherapy. However, the posttreatment NLR remained an independent predictor of PFS in the multivariate analysis (HR=2.23, 95% CI 1.15-2.321; P=0.001). A high posttreatment NLR was significantly associated with an increased risk of death (HR=1.87, 95% CI 0.89 3.31; P=0.037). CONCLUSION: A high posttreatment NLR is associated with poor prognostic factor. An early reduction in the NLR after treatment may indicate survival improvement in the patients. PMID- 27269177 TI - CXC chemokine CXCL12 tissue expression and circulating levels in peptic ulcer patients with Helicobacter pylori infection. AB - Helicobacter pylori (H. pylori) infection is among the most prevalent human infections. CXCL12 is a well-known CXC chemokine involved in inflammation and play major roles in angiogenesis. There is currently very limited data on the role of CXCL12 in peptic ulcer disease. Hence, we aimed to explore whether CXCL12 is involved in the pathogenesis of peptic ulcer induced by H. pylori. In this study, we enrolled 102 H. pylori-infected patients, including 51 with active ulcer (GA) and 51 with healing ulcer (GH). We also recruited 50 healthy subjects as control, which did not show any sign or symptoms of chronic inflammatory diseases, infection, or immune-related disorders. Endoscopy was performed to determine the stage of the disease. ELISA was used for detection of H. pylori infection and CXCL12 measurement. We also employed western blotting to detect CXCL12 in ulcerative lesions of H. pylori. Demographic data were also collected by questionnaire. Our results demonstrated that CXCL12 serum levels in GA group (151.8+/-18.31pg/mL) were significantly higher than those in GH (36.89+/ 6.78pg/mL) and control groups (33.77+/-9.12pg/mL) (P<0.0001). However, we did not observe a significant difference between GH and control groups. Moreover, overexpression of CXCL12 in gastric lesions of patients in GA group was confirmed by Western blot analysis. According to the result of the present study, it could be concluded that CXCL12 is involved in the pathogenesis and healing of H. pylori induced peptic ulcer. CXCL12 serum levels may also be used to distinguish between GA and GH phases of the disease. PMID- 27269134 TI - Monocyclic monoterpenes as penetration enhancers of ligustrazine hydrochloride for dermal delivery. AB - The purpose of this study was to explore the enhancing effects and the mechanism of monocyclic monoterpene penetration enhancers (menthol and menthone) on the transdermal absorption of ligustrazine hydrochloride (LH). Franz-type diffusion cells were used to determine percutaneous parameters of LH in vitro and surface changes of porcine skin were studied by a scanning electron microscope (SEM). The effects of promoters on the biophysical natures of stratum corneum (SC) were researched by Fourier transform-infrared (FT-IR). Penetration parameters of menthol (p < 0.01) and menthone groups (p < 0.05) were greater than those of the control; morphological changes of skin monitored by SEM demonstrated that the menthone group had the most disruption and desquamation of SC flakes, which resulted from extracted lipids. FT-IR measurements showed menthone had the greatest changes in peak shift and peak area, which resulted from C-H stretching vibrations of SC lipids. The results suggest that the penetration mechanism might include disturbing and extracting SC lipids and the hydrogen bond connection. PMID- 27269178 TI - Vitamin D status and its modulatory effect on interferon gamma and interleukin-10 production by peripheral blood mononuclear cells in culture. AB - OBJECTIVES: We aimed to investigate the influence of vitamin D on the production of the pro-inflammatory cytokine, interferon gamma (IFN-gamma), and the anti inflammatory cytokine, interleukin-10 (IL-10), in peripheral blood mononuclear cell (PBMC) cultures. METHODS: Thirty healthy subjects were investigated. Serum levels of calcium, 25(OH) D, and parathyroid hormone (PTH) were assessed. PBMCs were activated in-vitro by phytohemagglutinin (PHA) in the presence and absence of vitamin D3 and then levels of IFN-gamma and IL-10 were determined in culture supernatant using enzyme immunoassay. RESULTS: Serum calcium levels were significantly lower in the vitamin D deficient group while serum PTH levels were significantly higher in the vitamin D deficient group. PTH levels were inversely correlated to both calcium and 25(OH) D levels. In culture, vitamin D inhibited IFN-gamma production and increased IL-10 production by PBMCs. Serum vitamin D status had no influence on the amount of cytokine produced in culture. CONCLUSIONS: This study demonstrates that vitamin D modulates IFN-gamma and IL-10 production and provides a rationale for evaluating vitamin D as an immunomodulatory agent. PMID- 27269179 TI - Persistent elevated bone marrow plasma levels of thrombopoietin in patients with aplastic anemia. AB - Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure syndrome. Plasma thrombopoietin (TPO) levels are elevated in AA patients with reduced blood counts. However, whether elevated TPO can recover to normal level in AA patients in complete remission (CR) after efficient immunosuppressive therapy (IST) is unknown. We measured TPO levels of BM plasma in a large cohort of AA patients with focusing on patients in CR after IST. Our data showed that BM plasma TPO levels were still high in patients who had reached normal blood counts levels for a long time. We speculate that downregulated expression of MPL (TPO receptor) in HSPC (hematopoietic stem and progenitor cells) may be related to the upregulated TPO in AA. PMID- 27269180 TI - Associations between inflammatory cytokines and organ damage in pediatric patients with hemophagocytic lymphohistiocytosis. AB - Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease characterized by overwhelming inflammation response and multiple organ damage. Most of the clinical and laboratory manifestations of HLH are thought to be related to hypercytokinemia and organ infiltration with lymphocytes and histiocytes. The aim of this study was to investigate the associations between cytokines and various manifestations of HLH. A total of 105 patients diagnosed with HLH were enrolled in this retrospective study. The information including the patients' demographic characteristics, clinical and laboratory findings at presentation and cytokine data were collected. The median age at diagnosis was 2.8years, with 74 patients (70.4%) documented Epstein-Barr virus infection. Hepatomegaly (88.6%), splenomegaly (81.9%), cytopenia (68.6%), elevated ferritin level (93.3%), hypofibrinogenemia (61.9%) and hemophagocytosis (77.3%) were found in more than half of the patients. Interleukin (IL)-6, IL-10 and interferon (IFN) gamma were found to be moderately or significantly elevated in most patients. In the correlation analysis, IFN-gamma was closely related to the concentration of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, lactate dehydrase (LDH), triglyceride and fibrinogen, while IL-10 was associated with platelet count. When split the patients into two groups according to the cytokine levels, patients with high IFN-gamma presented higher level of ALT, AST, bilirubin, LDH, triglyceride, and fibrinogen, while patients with high IL-10 presented much lower hemoglobin and platelet count. In conclusion, the present study put forward clinical evidence that hypercytokinemia is related to organ damage in HLH. IFN-gamma may contribute to liver impairment and coagulation disease, while IL-10 is a cytokine related to cytopenias. PMID- 27269181 TI - IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose-dependently activated via IL-36beta and induces CD4+ lymphocyte proliferation. AB - We show that IL-36R is expressed by T (CD4+ and CD8+) and B (CD19+) lymphocytes in human blood and also by CD4+ T lymphocytes in the intestinal lamina propria. IL-36R protein was mostly stored in the cytoplasm of CD4 lymphocytes and B cells, during steady state conditions and the greatest expression of IL-36R mRNA was measured in CD4+ (T helper) lymphocytes. IL-36 beta, which functions via IL-36R induced rapid and significant (P<0.05) proliferation of CD4+ lymphocytes, within 48h. IL-36R expression was also maintained on the surface of circulating CD4+ lymphocytes which enter the intestinal lamina propria. In conclusion our study is the first to show that (1) all human blood lymphocytes express IL-36R; (2) IL-36R expression is maintained by circulating CD4+ lymphocytes which enter the intestinal lamina propria and (3) IL-36R/IL-36 beta induces rapid CD4 lymphocyte proliferation. The possible significance of these results in the context of human disease is discussed. PMID- 27269182 TI - Controlling the Motion of Ferrofluid Droplets Using Surface Tension Gradients and Magnetoviscous Pinning. AB - This work demonstrates the controlled motion and stopping of individual ferrofluid droplets due to a surface tension gradient and a uniform magnetic field. The surface tension gradients are created by patterning hydrophilic aluminum regions, shaped as wedges, on a hydrophobic copper surface. This pattern facilitates the spontaneous motion of water-based ferrofluid droplets down the length of the wedge toward the more hydrophilic aluminum end due to a net capillarity force created by the underlying surface wettability gradient. We observed that applying a magnetic field parallel to the surface tension gradient direction has little or no effect on the droplet's motion, while a moderate perpendicular magnetic field can stop the motion altogether effectively "pinning" the droplet. In the absence of the surface tension gradient, droplets elongate in the presence of a parallel field but do not travel. This control of the motion of individual droplets might lend itself to some biomedical and lab-on-a-chip applications. The directional dependence of the magnetoviscosity observed in this work is believed to be the consequence of the formation of nanoparticle chains in the fluid due to the existence of a minority of relatively larger magnetic particles. PMID- 27269183 TI - A proposal for prospective late outcome analysis of decellularized aortic valves. PMID- 27269184 TI - First case of Perceval S prosthesis early structural valve deterioration: Not an easy reoperation. PMID- 27269186 TI - Thrombotic thrombocytopenic pupura (TTP) dinner symposium proceedings. AB - Answering TTP was established to engage the thrombotic thrombocytopenic purpura (TTP) community to further the common goals of patient support, education of patients and medical professionals, and the funding of research to improve the treatment and care of TTP patients. Answering TTP convened a dinner symposium on 23 June 2015 in Toronto, Canada during the International Society of Thrombosis and Haemostasis (ISTH) Congress to bring TTP clinicians and research together to highlight the key clinical and research questions in the field. These questions are increasingly important given the recent advances and novel therapies that have or will soon enter clinical study for patients with TTP. PMID- 27269185 TI - Contributions of Phase, Sulfur Vacancies, and Edges to the Hydrogen Evolution Reaction Catalytic Activity of Porous Molybdenum Disulfide Nanosheets. AB - Molybdenum disulfide (MoS2) is a promising nonprecious catalyst for the hydrogen evolution reaction (HER) that has been extensively studied due to its excellent performance, but the lack of understanding of the factors that impact its catalytic activity hinders further design and enhancement of MoS2-based electrocatalysts. Here, by using novel porous (holey) metallic 1T phase MoS2 nanosheets synthesized by a liquid-ammonia-assisted lithiation route, we systematically investigated the contributions of crystal structure (phase), edges, and sulfur vacancies (S-vacancies) to the catalytic activity toward HER from five representative MoS2 nanosheet samples, including 2H and 1T phase, porous 2H and 1T phase, and sulfur-compensated porous 2H phase. Superior HER catalytic activity was achieved in the porous 1T phase MoS2 nanosheets that have even more edges and S-vacancies than conventional 1T phase MoS2. A comparative study revealed that the phase serves as the key role in determining the HER performance, as 1T phase MoS2 always outperforms the corresponding 2H phase MoS2 samples, and that both edges and S-vacancies also contribute significantly to the catalytic activity in porous MoS2 samples. Then, using combined defect characterization techniques of electron spin resonance spectroscopy and positron annihilation lifetime spectroscopy to quantify the S-vacancies, the contributions of each factor were individually elucidated. This study presents new insights and opens up new avenues for designing electrocatalysts based on MoS2 or other layered materials with enhanced HER performance. PMID- 27269187 TI - Velusetrag for the treatment of chronic constipation. AB - INTRODUCTION: Chronic constipation is a frequent complaint in daily clinical practice. Notwithstanding the availability of numerous drugs, its treatment it is still unsatisfactory. However, new emerging treatments are in the pipeline and some drugs seem to be promising; among these velusetrag, a selective 5-HT4 receptors agonist. AREAS COVERED: An in depth Medline literature search was performed concerning topics related to the treatment of constipated patients with velusetrag. In addition, abstracts concerning the topic were searched by hand in our libraries. EXPERT OPINION: After analyzing the available data, the authors feel that velusetrag may likely improve symptoms and the quality of life of chronically constipated subjects. However, additional data is needed to fully understand the safety and efficacy of velusetrag, particularly in patients on long-term therapy. Thanks to the once-daily dosing and the pharmacologic properties, velusetrag could be used as a single agent or in association with other drugs. In the future, this drug holds the potential to be an effective adjunct to the therapeutic armamentarium for chronic constipation. PMID- 27269188 TI - Immobilized Multifunctional Polymersomes on Solid Surfaces: Infrared Light Induced Selective Photochemical Reactions, pH Responsive Behavior, and Probing Mechanical Properties under Liquid Phase. AB - Fixing polymersomes onto surfaces is in high demand not only for the characterization with advanced microscopy techniques but also for designing specific compartments in microsystem devices in the scope of nanobiotechnology. For this purpose, this study reports the immobilization of multifunctional, responsive, and photo-cross-linked polymersomes on solid substrates by utilizing strong adamantane-beta-cyclodextrin host-guest interactions. To reduce nonspecific binding and retain better spherical shape, the level of attractive forces acting on the immobilized polymersomes was tuned through poly(ethylene glycol) passivation as well as decreased beta-cyclodextrin content on the corresponding substrates. One significant feature of this system is the pH responsivity of the polymersomes which has been demonstrated by swelling of the immobilized vesicles at acidic condition through in situ AFM measurements. Also, light responsivity has been provided by introducing nitroveratryloxycarbonyl (NVOC) protected amine molecules as photocleavable groups to the polymersome surface before immobilization. The subsequent low-energy femtosecond pulsed laser irradiation resulted in the cleavage of NVOC groups on immobilized polymersomes which in turn led to free amino groups as an additional functionality. The freed amines were further conjugated with a fluorescent dye having an activated ester that illustrates the concept of bio/chemo recognition for a potential binding of biological compounds. In addition to the responsive nature, the mechanical stability of the analyzed polymersomes was supported by computing Young's modulus and bending modulus of the membrane through force curves obtained by atomic force microscopy measurements. Overall, polymersomes with a robust and pH-swellable membrane combined with effective light responsive behavior are promising tools to design smart and stable compartments on surfaces for the development of microsystem devices such as chemo/biosensors. PMID- 27269189 TI - Towards a Mobile-Based Platform for Traceability Control and Hazard Analysis in the Context of Parenteral Nutrition: Description of a Framework and a Prototype App. AB - BACKGROUND: The parenteral nutrient (PN) mixtures may pose great risks of physical, microbiological, and chemical contamination during their preparation, storage, distribution, and administration. These potential hazards must be controlled under high levels of excellence to prevent any serious complications for the patients. As a result, management control and traceability of any of these medications is of utmost relevance for the patient care, along with ensuring treatment continuity and adherence. OBJECTIVE: The aim of this study is to develop a mobile-based platform to support the control procedures and traceability services in the domain of parenteral nutrient (PN) mixtures in an efficient and nonintrusive manner. METHODS: A comprehensive approach combining techniques of software engineering and knowledge engineering was used for the characterization of the framework. Local try-outs for evaluation were performed in a number of application areas, carrying out a test/retest monitoring to detect possible errors or conflicts in different contexts and control processes throughout the entire cycle of PN. From these data, the absolute and relative frequencies (percentages) were calculated. RESULTS: A mobile application for the Android operating system was developed. This application allows reading different types of tags and interacts with the local server according to a proposed model. Also, through an internal caching mechanism, the availability of the system is preserved even in the event of problems with the network connection. A set of 1040 test traces were generated for the assessment of the system under various environments tested. Among those, 102 traces (9.81%) involved conflictive situations that were properly taken care of in this paper by suggesting solutions to overcome them. CONCLUSIONS: A mobile oriented system was generated and tested in order to allow enhanced control and quality management of PN mixtures that is easy to integrate into the daily praxis of health care processes. PMID- 27269190 TI - COLORcation: A new application to phenotype exploratory behavior models of anxiety in mice. AB - BACKGROUND: Behavioral analyses in rodents have successfully delineated the function of many genes and signaling pathways in the brain. Behavioral testing uses highly defined experimental conditions to identify abnormalities in a given mouse strain or genotype. The open field (OF) is widely used to assess both locomotion and anxiety in rodents. In this test, the more a mouse explores and spend time in the center of the arena, the less anxious it is considered to be. However, the simplistic distinction between center and border substantially reduces the information content of the analysis and may fail to detect biologically meaningful differences. NEW METHOD: Here we describe COLORcation, a new application for improved analyses of mouse behavior in the OF. RESULTS: The application analyses animal exploration patterns in detailed spatial resolution (e.g. 10*10 bins) to provide a color-encoded heat map of mouse activity. In addition, COLORcation provides new parameters to track activity and locomotion of the test animals. We demonstrate the use of COLORcation in different experimental paradigms, including pharmacological and restraint-based induction of stress and anxiety. COMPARISON WITH EXISTING METHOD(S): COLORcation is compatible with multiple acquisition systems, giving users the option to make the most of their raw data organized text files containing time and coordinates of animal locations as input. CONCLUSION: These analyses validate the utility of the software and establish its reliability and potential as a new tool to analyze OF data. PMID- 27269191 TI - Stabilization of an axially moving accelerated/decelerated system via an adaptive boundary control. AB - In this study, an adaptive boundary control is developed for vibration suppression of an axially moving accelerated/decelerated belt system. The dynamic model of the belt system is represented by partial-ordinary differential equations with consideration of the high acceleration/deceleration and unknown distributed disturbance. By utilizing adaptive technique and Lyapunov-based back stepping method, an adaptive boundary control is proposed for vibration suppression of the belt system, a disturbance observer is introduced to attenuate the effects of unknown boundary disturbance, the adaptive law is developed to handle parametric uncertainties and the S-curve acceleration/deceleration method is adopted to plan the belt's speed. With the proposed control scheme, the well posedness and stability of the closed-loop system are mathematically demonstrated. Simulations are displayed to illustrate the effectiveness of the proposed control. PMID- 27269192 TI - Cage-rotor induction motor inter-turn short circuit fault detection with and without saturation effect by MEC model. AB - The inter-turn short fault for the Cage-Rotor-Induction-Machine (CRIM) is studied in this paper and its local saturation is taken into account. However, in order to observe the exact behavior of machine, the Magnetic-Equivalent-Circuit (MEC) and nonlinear B-H curve are proposed to provide an insight into the machine model and saturation effect respectively. The electrical machines are generally operated near to their saturation zone due to some design necessities. Hence, when the machine is exposed to a fault such as short circuit or eccentricities, it is operated within its saturation zone and thus, time and space harmonics are integrated and as a result, current and torque harmonics are generated which the phenomenon cannot be explored when saturation is dismissed. Nonetheless, inter turn short circuit may lead to local saturation and this occurrence is studied in this paper using MEC model. In order to achieve the mentioned objectives, two and also four-pole machines are modeled as two samples and the machines performances are analyzed in healthy and faulty cases with and without saturation effect. A novel strategy is proposed to precisely detect inter-turn short circuit fault according to the stator's lines current signatures and the accuracy of the proposed method is verified by experimental results. PMID- 27269193 TI - Novel application of continuously variable transmission system using composite recurrent Laguerre orthogonal polynomials modified PSO NN control system. AB - Because the V-belt continuously variable transmission system spurred by permanent magnet (PM) synchronous motor has much unknown nonlinear and time-varying characteristics, the better control performance design for the linear control design is a time consuming procedure. In order to overcome difficulties for design of the linear controllers, the composite recurrent Laguerre orthogonal polynomials modified particle swarm optimization (PSO) neural network (NN) control system which has online learning capability to come back to the nonlinear and time-varying of system, is developed for controlling PM synchronous motor servo-driven V-belt continuously variable transmission system with the lumped nonlinear load disturbances. The composite recurrent Laguerre orthogonal polynomials NN control system consists of an inspector control, a recurrent Laguerre orthogonal polynomials NN control with adaptation law and a recouped control with estimation law. Moreover, the adaptation law of online parameters in the recurrent Laguerre orthogonal polynomials NN is originated from Lyapunov stability theorem. Additionally, two optimal learning rates of the parameters by means of modified PSO are posed in order to achieve better convergence. At last, comparative studies shown by experimental results are illustrated to demonstrate the control performance of the proposed control scheme. PMID- 27269194 TI - A dual pH/Redox responsive copper-ligand nanoliposome bioactive complex for the treatment of chronic inflammation. AB - A novel dual pH/redox-responsive polymeric nanoliposome system (NLs) loaded with a copper-liganded bioactive complex was prepared and designed as a controlled delivery system for the management of inflammation. The NLs were synthesised after preparation of the copper-glyglycine-prednisolone succinate] ([(Cu(glygly)(PS)]) complex, and the dual pH/redox responsive biopolymer respectively. The methodology undertaken for the development of the drug delivery system involved coordination of the bioactive to Copper (II), preparation of dual pH/redox responsive biopolymer, and the synthesis of dual pH/redox nanoliposomes. Characterisations of the prepared copper-liganded bioactive [Copper-glyglycine prednisolone succinate] ([(Cu(glygly)(PS)]) complex, dual pH/redox responsive biopolymer (Eudragit E100-cystamine) and [(Cu(glygly)(PS)]-loaded NLs were carried out using spectroscopic and physicochemical techniques. Results indicated a high inflammatory/oxidant inhibitory activity of [Cu(glygly)(PS)] in comparison to the free PS drug. The [Cu(glygly)(PS)] complex exhibited a significant free radical-scavenging activity (60.1+/-1.2%) and lipoxygenase (LOX-5) inhibitory activity (36.6+/-1.3%) in comparison to PS which resulted in activity of 4.4+/ 1.4% and inhibition of 6.1+/-2.6% respectively. The [Cu(glygly)(PS)] loaded NLs demonstrated low release profiles of 22.9+/-5.4% in 6h at pH 7.4, in comparison to a significant accelerated release at pH 5 in a reducing environment of 75.9+/ 3.7% over 6h duration. Results suggest that the novel copper-liganded bioactive delivery system with controlled drug release mechanism could serve as a potential drug delivery system candidate in the management of inflammation. PMID- 27269195 TI - Risk factors for advanced resuscitation in term and near-term infants: a case control study. AB - OBJECTIVE: (1) To determine which antepartum and/or intrapartum factors are associated with the need for advanced neonatal resuscitation (ANR) at birth in infants with gestational age (GA) >=34 weeks. (2) To develop a risk score for the need for ANR in neonates with GA >=34 weeks. DESIGN: Prospective multicentre, case-control study. In total, 16 centres participated in this study: 10 in Argentina, 1 in Chile, 3 in Brazil and 2 in the USA. RESULTS: A case-control study conducted from December 2011 to April 2013. Of a total of 61 593 births, 58 429 were reported as an GA >=34 weeks, and of these, only 219 (0.37%) received ANR. After excluding 23 cases, 196 cases and 784 consecutive birth controls were included in the analysis. The final model was generated with three antepartum and seven intrapartum factors, which correctly classified 88.9% of the observations. The area under the receiver operating characteristic (AROC) performed to evaluate discrimination was 0.88, 95% CI 0.62 to 0.91. The AROC performed for external validity testing of the model in the validation sample was 0.87 with 95% CI 0.58 to 0.92. CONCLUSIONS: We identified 10 risk factors significantly associated with the need for ANR in newborns >=34 weeks. We developed a validated risk score that allows the identification of newborns at higher risk of need for ANR. Using this tool, the presence of specialised personnel in the delivery room may be designated more appropriately. PMID- 27269196 TI - A Single-Center Pilot Prospective Study of Topical Application of Platelet Derived Eye Drops for Patients with Ocular Chronic Graft-versus-Host Disease. AB - Ocular involvement of chronic graft-versus-host disease (cGVHD) is a complication that occurs in up to 60% of patients after allogeneic hematopoietic stem cell transplantation. Conventional therapeutic options include medical and surgical procedures that are administered depending on the severity of the condition, but most of them have provided unsatisfactory results and, to date, there is no consensus about treatment. We considered that topical application of a platelet lysate, administered as eye drops, might be considered an alternative worthwhile of investigation to treat ocular surface disorders in patients suffering from cGVHD. Therefore, we conducted a single-center prospective pilot study to assess the efficacy and safety of using eye drops made from reconstituted lysed platelet concentrate. Twenty-six patients with ocular cGVHD were eligible for the study; all but 2 completed their scheduled 1-year treatment and complied with the hematologic and ophthalmic regimen. At their first assessment interviews, after 30 days of treatment, 91% of patients reported an improvement in their symptoms and for 32%, substantive objective differences were measured. Remission of corneal damage was seen for 86% of our cohort, and improved National Institutes of Health scores for 73%, of whom 8% achieved the best score of 0 (ie, non-dry eye). Similar results were seen at later time points. Comparing outcomes for our patient cohort to those determined retrospectively for patients in our institutional database revealed a 5-year overall survival (OS) of 65%. This OS is comparable to patients with limited cGVHD (75%) and is superior to that of patients with nonocular extensive cGVHD or without cGVHD (30% and 59%, respectively) (P = .013). Our results suggest that platelet-derived eye drops are a safe, practical, and well-tolerated therapeutic option that offers substantial benefits for most patients affected by ocular cGVHD at onset. The favorable OS of our patient cohort suggests that this topical therapy, rather than systemic immunosuppression, may be the treatment of choice. PMID- 27269197 TI - Swallowing disorders in Parkinson's disease. AB - INTRODUCTION: Parkinson's disease is a type of chronic neurodegenerative pathology with a typical movement pattern, as well as different, less studied symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonias. The aim of this study was identifying and analyzing swallowing disorders in Parkinson's disease. SUBJECTS AND METHODS: The initial sample consisted of 52 subjects with Parkinson's disease to whom the specific test for dysphagia SDQ was applied. Nineteen participants (36.5%) with some degree of dysphagia in the SDQ test were selected to be evaluated by volume-viscosity clinical exploration method and fiberoptic endoscopic evaluation of swallowing. RESULTS: Disorders in swallowing efficiency and safety were detected in 94.7% of the selected sample. With regards to efficiency, disorders were found in food transport (89.5%), insufficient labial closing (68.4%) and oral residues (47.4%), relating to duration of ingestion. Alterations in security were also observed: pharynx residues (52.7%), coughing (47.4%), penetration (31.64%), aspiration and decrease of SaO2 (5.3%), relating to the diagnosis of respiratory pathology in the previous year. CONCLUSION: The SDQ test detected swallowing disorders in 36.5% of the subjects with Parkinson's disease. Disorders in swallowing efficiency and safety were demonstrated in 94.7% of this subset. Disorders of efficiency were more frequent than those of safety, establishing a relationship with greater time in ingestion and the appearance of respiratory pathology and pneumonias. PMID- 27269198 TI - Bacterial Peptide deformylase inhibition of cyano substituted biaryl analogs: Synthesis, in vitro biological evaluation, molecular docking study and in silico ADME prediction. AB - Herein, we report the synthesis and screening of cyano substituted biaryl analogs 5(a-m) as Peptide deformylase (PDF) enzyme inhibitors. The compounds 5a (IC50 value=13.16MUM), 5d (IC50 value=15.66MUM) and 5j (IC50 value=19.16MUM) had shown good PDF inhibition activity. The compounds 5a (MIC range=11.00-15.83MUg/mL), 5b (MIC range=23.75-28.50MUg/mL) and 5j (MIC range=7.66-16.91MUg/mL) had also shown potent antibacterial activity when compared with ciprofloxacin (MIC range=25 50MUg/mL). Thus, the active derivatives were not only potent PDF inhibitors but also efficient antibacterial agents. In order to gain more insight on the binding mode of the compounds with PDF, the synthesized compounds 5(a-m) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates. PMID- 27269199 TI - Low serotonin1B receptor binding potential in the anterior cingulate cortex in drug-free patients with recurrent major depressive disorder. AB - The pathophysiology of major depressive disorder (MDD) is not fully understood and the diagnosis is largely based on history and clinical examination. So far, several lines of preclinical data and a single imaging study implicate a role for the serotonin1B (5-HT1B) receptor subtype. We sought to study 5-HT1B receptor binding in brain regions of reported relevance in patients with MDD. Subjects were examined at the Karolinska Institutet PET centre using positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369. Ten drug-free patients with recurrent MDD and ten control subjects matched for age and sex were examined. The main outcome measure was [(11)C]AZ10419369 binding in brain regions of reported relevance in the pathophysiology of MDD. The [(11)C]AZ10419369 binding potential was significantly lower in the MDD group compared with the healthy control group in the anterior cingulate cortex (20% between-group difference), the subgenual prefrontal cortex (17% between-group difference), and in the hippocampus (32% between-group difference). The low anterior cingulate [(11)C]AZ10419369 binding potential in patients with recurrent MDD positions 5-HT1B receptor binding in this region as a putative biomarker for MDD and corroborate a role of the anterior cingulate cortex and associated areas in the pathophysiology of recurrent MDD. PMID- 27269200 TI - Children in clinical trials: towards evidence-based pediatric pharmacotherapy using pharmacokinetic-pharmacodynamic modeling. AB - INTRODUCTION: In pediatric pharmacotherapy, many drugs are still used off-label, and their efficacy and safety is not well characterized. Different efficacy and safety profiles in children of varying ages may be anticipated, due to developmental changes occurring across pediatric life. AREAS COVERED: Beside pharmacokinetic (PK) studies, pharmacodynamic (PD) studies are urgently needed. Validated PKPD models can be used to derive optimal dosing regimens for children of different ages, which can be evaluated in a prospective study before implementation in clinical practice. Strategies should be developed to ensure that formularies update their drug dosing guidelines regularly according to the most recent advances in research, allowing for clinicians to integrate these guidelines in daily practice. Expert commentary: We anticipate a trend towards a systems-level approach in pediatric modeling to optimally use the information gained in pediatric trials. For this approach, properly designed clinical PKPD studies will remain the backbone of pediatric research. PMID- 27269201 TI - Match play demands of 11 versus 11 professional football using Global Positioning System tracking: Variations across common playing formations. AB - This study aimed to examine Global Positioning System (GPS) determined movement patterns across the 5 most common playing formations (4-4-2; 4-3-3; 3-5-2; 3-4-3; 4-2-3-1) employed in 11 versus 11 football match play in England. Elite male footballers (n=46) were monitored over the course of a season; total distance (TD), high speed running (HSR), high metabolic load distance (HMLD), high speed accelerations (Acc) and decelerations (Dec) data was collected for analysis. It was found that 3-5-2 formation elicited higher TD (10528+/-565m, p=0.05), HSR (642+/-215m, p=0.001), and HMLD (2025+/-304m, p=0.001) than all other formations and above average Acc and Dec (34+/-7, p=0.036 and 57+/-10, p=0.006), with 4-2-3 1 eliciting the highest Acc and Dec (38+/-8 and 61+/-12). Positional data showed that CM in 4-3-3 covered >11% TD than in 4-4-2 (p=0.012). FW in 3-5-2 covered >45% HSR than in 4-2-3-1 (p=0.004). CM in 4-3-3 covered >14% HMLD than in 4-4-2 (p=0.367). FW in 4-3-3 performed >49% accelerations than in 4-2-3-1 (p=0.293). WD in 3-5-2 performed >20% more decelerations than in 4-4-2 (p=0.161). This study is important for coaches understanding, that positional physical characteristics are influenced by the demands of playing in different formations during match play. PMID- 27269202 TI - Veterinary clinical nutrition: success stories: an overview. AB - In this overview of success stories in veterinary clinical nutrition topics in cats and dogs reviewed include the dietary management of chronic kidney disease, dissolution of urinary tract uroliths by dietary modification, the recognition that taurine and L-carnitine deficiencies can cause dilated cardiomyopathy; that clinical signs associated with feline hyperthyroidism (caused by a benign adenoma) can be controlled by a low-iodine diet alone; that dietary management of canine osteoarthritis can also reduce non-steroidal anti-inflammatory drug doses; and that disease-free intervals and survival times can be statistically longer in dogs with Stage III lymphoma managed with diet. As we discover more about nutrigenetics and nutrigenomics, and as we expand our basic understanding of idiopathic diseases we are bound to identify more nutritionally related causes, and be able to develop novel dietary strategies to manage disease processes, including the formulation of diets designed to alter gene expression to obtain beneficial clinical outcomes. PMID- 27269203 TI - Elucidating the influence of praziquantel nanosuspensions on the in vivo metabolism of Taenia crassiceps cysticerci. AB - The aim of this work was to develop nanosuspensions of praziquantel (PZQ) and to evaluate their influence on the energetic metabolism of cysticerci inoculated in BALB/c mice. We analyzed metabolic alterations of glycolytic pathways and the tricarboxylic acid cycle in the parasite. The nanosuspensions were prepared by precipitation and polyvinyl alcohol (PVA), poloxamer 188 (P188) and poloxamer 407 (P407) were used as stabilizers. Nanosuspension prepared with PVA had a particle size of 100nm, while P188- and P407-based nanosuspensions had particle sizes of 74nm and 285nm, respectively. The zeta potential was -8.1, -8.6, and -13.2 for the formulations stabilized with PVA, P188 and P407, respectively. Treatments of T. crassiceps cysticerci-infected mice resulted in an increase in glycolysis organic acids, and enhanced the partial reversion of the tricarboxylic acid cycle, the urea cycle and the production of ketonic bodies in the parasites when compared to the groups treated with conventional PZQ. These data suggest that PZQ nanosuspensions greatly modified the energetic metabolism of cysticerci in vivo. Moreover, the remarkable metabolic alterations produced by the stabilizers indicate that further studies on nanoformulations are required to find potentially suitable nanomedicines. PMID- 27269204 TI - Hybrid Biomaterial with Conjugated Growth Factors and Mesenchymal Stem Cells for Ectopic Bone Formation. AB - Bone is a highly vascularized tissue and efficient bone regeneration requires neovascularization, especially for critical-sized bone defects. We developed a novel hybrid biomaterial comprising nanocalcium sulfate (nCS) and fibrin hydrogel to deliver mesenchymal stem cells (MSCs) and angiogenic factors, vascular endothelial growth factor (VEGF) and fibroblast growth factor 9 (FGF9), to promote neovascularization and bone formation. MSC and growth factor(s)-loaded scaffolds were implanted subcutaneously into mice to examine their angiogenic and osteogenic potential. Micro CT, alkaline phosphatase activity assay, and histological analysis were used to evaluate bone formation, while immunohistochemistry was employed to assess neovessel formation. The presence of fibrin preserved the nCS scaffold structure and promoted de novo bone formation. In addition, the presence of bone morphogenic protein 2-expressing MSC in nCS and fibrin hydrogels improved bone regeneration significantly. While FGF9 alone had no significant effect, the combination FGF9 and VEGF conjugated in fibrin enhanced neovascularization and bone formation more than 4-fold compared to nCS with MSC. Overall, our results suggested that the combination of nCS (to support bone formation) with a fibrin-based VEGF/FGF9 release system (support vascular formation) is an innovative and effective strategy that significantly enhanced ectopic bone formation in vivo. PMID- 27269205 TI - Unilateral and bilateral MRI-targeted repetitive transcranial magnetic stimulation for treatment-resistant depression: a randomized controlled study. AB - BACKGROUND: Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to cortex distance). METHODS: We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. RESULTS: A total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups. LIMITATIONS: The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation. CONCLUSION: Our findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates. PMID- 27269206 TI - Long-term fatigue after perimesencephalic subarachnoid haemorrhage in relation to cognitive functioning, mood and comorbidity. AB - PURPOSE: To study relationships between fatigue and objective and subjective cognitive functioning, mood and comorbidity in the long term after perimesencephalic subarachnoid haemorrhage (PM-SAH). METHODS: Cross-sectional study. Objective cognitive functioning was measured with: Trail Making Test; Symbol Substitution; D2; Verbal and Semantic Fluency; Tower Test; Digit Span; 15 Words Test; Rey Complex Figure. Subjective cognitive functioning: Cognitive Failure Questionnaire. Fatigue: Fatigue Severity Scale. Mood: Hospital Anxiety and Depression Scale. RESULTS: Forty-six patients, mean age 50.4 (SD = 9.4), mean time after PM-SAH 4.7 (SD = 1.6) years participated. Patients with fatigue (33%) had significantly lower scores than patients without fatigue on most objective cognitive functioning tests (p < 0.05). Fatigue score was significantly associated with subjective and objective cognitive functioning, mood and comorbidity. After adjustment for mood and comorbidity, fatigue remained associated with attention and executive functioning. CONCLUSIONS: This study supports our previous findings that a third of patients with PM-SAH experience fatigue and problems of cognitive functioning, also in the long term. Future research should investigate whether these patients would benefit from long-term follow-up and/or cognitive rehabilitation programmes. Implications for Rehabilitation Consequences for patients with PM-SAH are underestimated. One in every three patients suffered from fatigue in the long term after onset of PM SAH. Patients with PM-SAH should be screened for problems of cognitive functioning, fatigue and mood in outpatient clinic just as patients with aneurysmal SAH. PMID- 27269207 TI - First Experience with Three-Dimensional Thoracolaparoscopy in Esophageal Cancer Surgery. AB - INTRODUCTION: Endoscopic techniques are rapidly gaining interest in esophageal cancer surgery due to lower pulmonary complication rates and faster postoperative recovery. Conventional two-dimensional endoscopic surgery has two main limitations: lack of depth perception and limited dexterity due to the use of rigid instruments. Theoretically, three-dimensional (3D) endoscopy can overcome these limitations, but to date, its use has not been reported in the context of esophageal cancer surgery. We studied our first series of 3D thoracolaparoscopic esophagectomies to document the safety and feasibility of implementing this technique. METHODS: Patients who underwent a thoracolaparoscopic esophagectomy using a glasses-based 3D system with a 100 degrees angulating camera tip were included. Continuity of the digestive tract was restored with gastric tube reconstruction and a cervical anastomosis. RESULTS: All 13 resections were completed thoracolaparoscopically. Median duration of surgery was 360 minutes (range: 245-590 minutes), and median blood loss was 170 mL (range: 50-230 mL). A median of 20 lymph nodes was resected, and all resections were microscopically radical. Median hospital stay was 9 days. Two patients developed pneumonia (15%), and three patients experienced an anastomotic leakage (23%). All postoperative complications were managed on the ward. CONCLUSION: In this series, the newest generation glasses-based 3D systems proved safe and useful for the thoracolaparoscopic resection of esophageal cancer. Besides better visualization, dexterity seemed to be improved using the 100 degrees flexible 3D camera. Implementation was without significant problems, and the first results are promising. PMID- 27269212 TI - What Do All the Numbers Mean? PMID- 27269211 TI - Track-Density Imaging of the Human Brainstem for Anatomic Localization of Fiber Tracts and Nerve Nuclei in Vivo: Initial Experience with 3-T Magnetic Resonance Imaging. AB - BACKGROUND: The brainstem comprises a large variety of fiber tracts and nerve nuclei and is unarguably one of the most crucial parts of the brain. Reliable noninvasive visualization of its anatomy may help relate normal and pathological anatomic variations to neurologic/psychiatric disorders. In this study, we explored the potential of direction-encoded track-density imaging (TDI) for depicting the intricate anatomy of the brainstem. METHODS: A total of 18 healthy volunteers (10 females, 8 males; median age, 34.5 years; interquartile range, 31 44.5 years) were examined on a 3-T MRI system. Diffusion tensor imaging data were processed using MRtrix to generate TDI images. These images were then compared with anatomic atlases to identify nerve nuclei and fiber tracts. The ability of TDI to delineate anatomic structures in the mesencephalon, pons, and medulla oblongata was evaluated using a 6-point Likert scale (5, excellent; 4, good; 3, moderate; 2, poor; 1, no adequate differentiation; 0, evaluation not possible). RESULTS: All generated TDI images were evaluable without limitations. In the mesencephalon, delineation of the substantia nigra, crus cerebri, and red nucleus was rated as excellent, that of the medial lemniscus was rated as good, and that of the inferior colliculus was rated as poor. Delineation of all anatomic structures in the pons was rated as excellent. In the medulla oblongata, delineation of the pyramid was rated as excellent and that of the medial lemniscus as moderate, whereas delineation of the inferior olive was not possible. CONCLUSIONS: TDI images provide optimal delineation of nerve nuclei and fibers in the upper brainstem, but have more difficulty identifying more caudal structures. PMID- 27269210 TI - Invasive Giant Cell Tumor of the Lateral Skull Base: A Systematic Review, Meta Analysis, and Case Illustration. AB - BACKGROUND: The current literature regarding cranial giant cell tumor (GCT) management includes scattered case reports and small case series. We present a comprehensive literature review and meta-analysis on this subject, along with a case report describing our management of a patient with temporal GCT. METHODS: A systematic literature review of all reports on GCTs of the skull was performed, followed by a meta-analysis examining the effect of radiation and degree of resection on tumor recurrence. RESULTS: Fifty-nine abstracts published between 1945 and 2015, reporting 110 cases of GCT, were reviewed. After exclusions were applied, 31 reports, covering 67 patients, were selected for meta-analysis. Average patient age was 33.7 years, and the male:female ratio was roughly 1:1. Tumor locations were temporal in 37 patients, sphenoid in 20 patients, occipital in 6 patients, frontal in 2 patients, and the temporomandibular joint in 2 patients. Treatments were surgery plus radiation in 25 patients, surgery alone in 41 patients, and radiation alone in 1 patient. In the 66 patients who underwent surgery, the degree of resection was gross total resection (GTR) in 34 patients, subtotal resection (STR) in 31 patients, and not recorded in 1 patient. The mean follow-up time was 36 months. Recurrence occurred in 8.8% of patients in the GTR group and in 32.3% of those in the STR group (odds ratio, 0.203; 95% confidence interval, 0.033-0.937; P = 0.018). The odds ratio for STR alone compared with STR plus radiation was 14.01 (P = 0.0038). CONCLUSION: GCTs of the skull commonly affect young adults, with an equal sex distribution, and are most often centered in temporal bone. GTR is associated with the lowest recurrence rate and should be the goal of treatment. If GTR cannot be achieved, the combination of STR and radiation results in a similar recurrence rate. With the advent of denosumab, there is now a role for chemotherapy in the treatment of GCTs. PMID- 27269213 TI - [Not Available]. PMID- 27269214 TI - [Not Available]. AB - El cancer es un problema sanitario de primera magnitud a escala mundial. Su tratamiento es uno de los mayores campos de innovacion y desarrollo en medicina. La vision del cancer como una enfermedad sistemica, heterogenea y de una elevada complejidad hace que los enfermos deban recibir una atencion oncologica de calidad, proporcionada por equipos multidisciplinares altamente cualificados. Ademas de la gran incidencia de malnutricion en estos pacientes, la intervencion nutricional precoz puede mejorar su pronostico, aumentar la calidad de vida y disminuir la tasa de complicaciones de la enfermedad. Por ello, es necesaria una estrecha colaboracion entre el oncologo y el experto en nutricion. PMID- 27269215 TI - [Not Available]. AB - El sindrome de caquexia cancerosa es responsable de la muerte de un numero significativo de pacientes con cancer. Se caracteriza por la presencia de una ingesta reducida, con inflamacion sistemica y un metabolismo alterado. Los enfermos presentan caracteristicamente una progresiva perdida de peso y de masa muscular, junto a deterioro funcional. La perdida muscular se debe a la combinacion de reduccion de la sintesis proteica con aumento de su degradacion. Ello conduce tanto a un acortamiento como a una reduccion en el area de la fibra muscular. Asimismo, existen datos que apoyan que selectivamente algunos de los tipos de fibra muscular se ven mas afectados. Es necesario definir bien los valores de corte de sarcopenia para diagnosticar la perdida muscular y existen diferentes metodos. El sistema de la ubiquitina-proteasoma parece desempenar un papel predominante en la degradacion de la proteina miofibrilar. La tendencia a perder masa muscular en los pacientes con caquexia cancerosa parece estar asociada a la activacion de senales catabolicas por citoquinas proinflamatorias, asi como por productos tumorales del tipo factor inductor de proteolisis. En referencia a los factores pronosticos, el riesgo de muerte esta bien documentado en pacientes con sarcopenia y, especialmente, en aquellos con obesidad asociada a la sarcopenia. Asimismo, se ha establecido una relacion directa entre la perdida intensa de masa muscular y la supervivencia en pacientes con diferentes tipos de tumores del tipo de cancer de pancreas, pulmon, tracto biliar o cancer colorrectal. Respecto de la terapia en el sindrome de caquexia cancerosa, es factible que requiera tratamiento con varios grupos combinados que incluyan, junto al soporte nutricional, farmacos orexigenos, con efecto anabolico y antinflamatorio, asociados a intervenciones que estimulen el ejercicio fisico. PMID- 27269216 TI - [Not Available]. AB - La atencion nutricional en el paciente oncohematologico debe formar parte del tratamiento global del paciente. Las alteraciones debidas a la localizacion de la neoplasia y los efectos secundarios del tratamiento oncoespecifico muchas veces dificultan o impiden la alimentacion oral. Esto puede dar lugar a una desnutricion y es de gran importancia su deteccion, valoracion e intervencion temprana. El primer paso en la intervencion nutricional es el consejo dietetico. Este articulo muestra que aspectos deben tenerse en cuenta para poder elaborar un consejo dietetico y la importancia de que este sea individualizado. Se describen como ejemplo cuatro situaciones especiales, donde es necesario trasladar las recomendaciones nutricionales a un plan dietetico. Tambien se incide en el uso de los probioticos en pacientes inmunocomprometidos. PMID- 27269217 TI - [Not Available]. AB - Cada vez es mayor el numero de ancianos con diagnostico de cancer que acuden a las consultas de Oncologia Medica. El proceso del envejecimiento y la gran variabilidad existente en la poblacion geriatrica implican que, para hacer un abordaje adecuado del paciente, se deba considerar la edad fisiologica del anciano, y no su edad biologica. Para ello, es preciso hacer una evaluacion somera, especifica e individualizada a cada uno de los ancianos con diagnostico de cancer que acudan a nuestra consulta. La valoracion geriatrica integral (VGI) es la herramienta clave que permite evaluarlos de forma adecuada, e incluso orienta la toma de decisiones "personalizada" en los ancianos con diagnostico de cancer. Dado que la VGI consume mucho tiempo en la consulta diaria, se estan desarrollando distintas herramientas de cribado que permitan acortar la atencion al paciente, al seleccionar aquellos ancianos que deban someterse a una VGI y aquellos en los que esta no sea necesaria. Se han publicado distintos modelos de VGI en la Oncogeriatria y se han desarrollado distintas herramientas de cribado de fragilidad; los mas conocidos son el cuestionario Vulnerable Elders Survey-13 (VES-13) y el cuestionario G-8. En este articulo se hace una revision acerca de la evidencia cientifica existente en cuanto a la atencion y valoracion del anciano oncologico, asi como los distintos parametros de los que se disponen para la toma de decisiones definitiva. Dichos datos reflejan el papel de la Oncogeriatria como la via para ofrecer una atencion global optima a este grupo poblacional. PMID- 27269218 TI - [Not Available]. AB - En la actualidad existe una alta variabilidad en la practica clinica en nutricion que podria afectar al estado nutricional de los pacientes oncologicos. La implementacion de guias de practica clinica de adecuada calidad puede ayudarnos a disminuir esta variabilidad y minimizar los efectos deletereos de la malnutricion en los pacientes oncologicos. Las guias suelen estar basadas en la evidencia, formulando las recomendaciones a partir de la mejor informacion disponible. No obstante, es importante tener en cuenta la calidad metodologica en la elaboracion de las guias y valorar si existen conflictos de interes. Los principales problemas de las guias actuales suelen ser que existe limitada evidencia de alta calidad, y que las recomendaciones basadas exclusivamente en la evidencia pueden no ser utiles en la practica clinica diaria, ya que no tienen en cuenta la aplicabilidad que es fundamental para su implementacion. Por otro lado, las guias clinicas hasta la actualidad han sido inconsistentes en la forma de evaluar la calidad de la evidencia y el grado de recomendacion. Como resultado, los usuarios se enfrentan al desafio de comprender los mensajes que los diferentes sistemas de grados de evidencia tratan de comunicar. En esta revision se realiza un resumen de las recomendaciones de las principales guias clinicas sobre valoracion y/o soporte nutricional en pacientes oncohematologicos desarrolladas en los ultimos 10 anos, incluyendo algunas guias de calidad de sociedades cientificas que no son accesibles a traves de las bases de datos comunmente usadas como PubMed. PMID- 27269219 TI - [Not Available]. AB - Durante la ultima decada, el conocimiento de nuevos mecanismos implicados en el desarrollo del cancer ha permitido el diseno de nuevos farmacos para su tratamiento y la mayor parte de ellos son farmacos que se administran por via oral. Uno de los principales problemas de los pacientes oncohematologicos es la desnutricion, que suele tener causas multifactoriales (de la propia enfermedad, de los pacientes y de los diferentes tratamientos administrados). Para minimizar el impacto de la desnutricion es necesaria una intervencion nutricional, ya sea adaptando la dieta o mediante la instauracion de soporte nutricional artificial, en funcion de la gravedad de cada caso. En cualquier paciente que este recibiendo un tratamiento oncologico hay que evaluar las posibles interacciones que pueden existir con el soporte nutricional instaurado, ya sea dieta oral, suplementacion oral o nutricion enteral. Estas interacciones pueden disminuir la eficacia, aumentar la toxicidad de los tratamientos o producir deficits nutricionales. Se detallan las principales interacciones que se pueden producir, las interacciones entre los tratamientos oncologicos y el soporte nutricional. PMID- 27269220 TI - [Not Available]. AB - Los datos del estudio PREDYCES(r) nos revelaron que en Espana la desnutricion relacionada con la enfermedad (DRE) afecta a uno de cada cuatro pacientes hospitalizados. Esta cifra aumenta hasta el 36,8% en los pacientes hematologicos. Se calcula que un 20% de los pacientes oncologicos muere por complicaciones relacionadas con la DRE. Nuestro grupo se planteo en 2011 comenzar la implantacion de un cribado nutricional en los servicios con mayor riesgo de DRE. La presente revision trata de describir todo el proceso que hemos seguido para mejorar la situacion nutricional en los pacientes ingresados en el Servicio de Hematologia del Complejo Asistencial Universitario de Leon (CAULE), mayoritariamente con diagnostico de neoplasias hematologicas. En un primer estudio piloto, detectamos una alta prevalencia de desnutricion, que tendio a aumentar durante la hospitalizacion. Ademas, solo el 8,3% los enfermos valorados recibieron algun tipo de soporte nutricional y no se estaban cubriendo sus necesidades ni caloricas ni proteicas, lo que se asociaba a un peor pronostico. Por este motivo, nos decidimos a implantar de manera sistematica un cribado y una intervencion nutricional adecuada, que comenzo en 2011 y que ha recibido el reconocimiento como Buena Practica del Sistema Nacional de Salud. PMID- 27269221 TI - Three-dimensional evaluation of the alar cinch suture after Le Fort I osteotomy. AB - Orthognathic surgery has an influence on the overlying soft tissues of the translated bony maxillomandibular complex. Improvements in both function and facial appearance are the goals of surgery. However, unwanted changes to the soft tissues, especially in the nose region, frequently occur. The most common secondary change in the nasolabial region is widening of the alar base. Various surgical techniques have been developed to minimize this effect. The purpose of this study was to evaluate the changes in the nasal region due to orthognathic surgery, especially the alar width and nasal volume, using combined cone beam computed tomography (CBCT) and three-dimensional (3D) stereophotogrammetry datasets. Twenty-six patients who underwent a Le Fort I advancement osteotomy between 2006 and 2013 were included. From 2006 to 2010, no alar base cinch sutures were performed. From 2010 onwards, alar base cinch sutures were used. Preoperative and postoperative documentation consisted of 3D stereophotogrammetry and CBCT scans. 3D measurements were performed on the combined datasets, and the alar base width and nose volume were analyzed. No difference in alar base width or nose volume was observed between patients who had undergone an alar cinch and those who had not. Postoperatively the nose widened and the volume increased in both groups. PMID- 27269223 TI - Editorial note on journal style. PMID- 27269222 TI - Three-dimensional virtual simulation of alar width changes following bimaxillary osteotomies. AB - The aim of this study was to evaluate the accuracy of three-dimensional (3D) soft tissue simulation of nose width changes following bimaxillary osteotomies and to identify patient- and surgery-related factors that may affect the accuracy of simulation. Sixty patients (mean age 26 years) who underwent bimaxillary osteotomies participated in this study. Cone beam computed tomography scans were acquired preoperatively and at 1-year postoperative. The 3D hard and soft tissue rendered preoperative and postoperative virtual head models were superimposed, after which the maxilla and mandible were segmented and aligned to the postoperative position. The postoperative changes in alar width were simulated using a mass tensor model (MTM)-based algorithm and compared with the postoperative outcome. 3D cephalometric analyses were used to quantify the simulation error. The postoperative alar width was increased by 1.6+/-1.1mm and the mean error between the 3D simulation and the actual postoperative alar width was 1.0+/-0.9mm. The predictability was not correlated to factors such as age, sex, alar cinch suture, VY closure, maxillary advancement, or a history of surgically assisted rapid maxillary expansion. The MTM-based simulation model of postoperative alar width change was found to be reasonably accurate, although there is room for further improvement. PMID- 27269224 TI - When the field is a ward or a clinic: Hospital ethnography. PMID- 27269225 TI - Negotiated interactive observation: Doing fieldwork in hospital settings. AB - In this paper I discuss the possibilities and limitations of the ethnographer participating in the different on-going activities and events in highly specialised healthcare systems. The concept of participant observation is based on a number of assumptions, particularly that the ethnographer will become one of 'them' to be able to follow the steps belonging to the accepted ethnographic research practice of doing fieldwork. The character of fieldwork in highly specialised healthcare systems does not fit well with this assumption. I suggest that we need to rethink the concept of participant observation and I propose negotiated interactive observation as a more appropriate way to describe ethnographic fieldwork in a setting such as the hospital or the clinic. PMID- 27269226 TI - 'Untangling the web of critical incidents': Ethnography in a paediatric setting. AB - Critical incidents (CIs) are the elements that bring about an alert or wake up call for clinicians in hospital wards. They are considered critical because the safety of patients, staff or visitors is at risk. Not all CIs result in dire consequences, nor do they require Root Cause Analysis (RCA). Nonetheless, incidents affect patients and involve clinicians' interactions with each other. This paper describes the complexities embedded in two CIs in a major paediatric hospital in Australia. An anthropological ethnographic research approach enabled the researcher to observe, document, interpret and make sense of the activities of clinicians in two different clinical areas of the hospital, i.e., the Rehabilitation Unit and the Neonatal Unit (NU). Ethnographic research significantly exposes and highlights hospital dramas and shows the effects on clinicians' everyday lives. We suggest that CIs have two dimensions: a medical and a social. The medical dimension encompasses factors in the treatment and care of the patient. The social dimension encompasses the social relationships and the socio-affectivity (emotional responses and labour) of treating clinicians. Our main argument is that foregrounding of the socio-cultural dimensions of CIs informs and impacts on the medical dimensions. Our conclusions demonstrate that the social dimensions of CIs have important ramifications for clinical interactions in everyday practices and these impact on the positive learning of clinicians after a CI has occurred. PMID- 27269227 TI - What's in a rehab? Ethnographic evaluation research in Indigenous Australian residential alcohol and drug rehabilitation centres. AB - Residential rehabilitation centres are a popular form of treatment for Indigenous Australians suffering from alcohol and drug misuse; however, there has been very little substantive research and evaluation in this area. Based on long-term ethnographic research, this study examines the informal aspects of a treatment programme in an Indigenous residential alcohol and drug rehabilitation service. Evaluation of such services often focuses on treatment length and/or treatment level obtained as key indicators of success. This study suggests that 'treatment' may be more complex and layered with multiple levels of meaning, which may not necessarily be captured in some evaluation designs. For the residential rehabilitation centre discussed in this paper, oscillating periods of mutual support and discipline have an important therapeutic function. Standard measures of treatment length and level obtained are meaningless without incorporating understanding of this process. This paper presents some of the ethnographic findings, alongside some of the evaluation implications of doing this kind of research. PMID- 27269228 TI - Patients' perspectives on hospitalisation: Experiences from a cancer ward in Kenya. AB - This paper explores how adult cancer in-patients feel about and make sense of their condition and therapy. Data was collected through observation and informal conversations with patients and hospital staff, over a period of 12 months, on a cancer ward in a teaching hospital in Kenya. I held in-depth conversations on multiple occasions with 42 patients. Most of them expected to recover quite fully, despite having postponed seeking medical help, and delays in referral. Long periods of suffering, prolonged diagnosis and treatment, and socio-economic difficulties shape the patients' perspectives on hospitalisation. The low position of patients in the social and medical hierarchy, and inadequate hospital resources, hamper their capacity to negotiate their care. The needs of the cancer patients can better be met when their experiences during hospitalisation are understood. This can foster co-operation between patients and hospital staff to facilitate coping with chronic illness. The patients' views highlight both material and non-material needs in cancer management in a developing country. PMID- 27269229 TI - Death dwells in spaces: Bodies in the hospital mortuary. AB - This paper explores the idea of death spaces, in particular the ways that diverse, at times disruptive, meanings about the dead are inscribed in mortuary spaces. The author draws upon data from an ethnographic study based in a hospital's Department of Anatomical Pathology to introduce the concept of three co-constructed spaces: that of sentiment, science and spirit. The author explores the daily interactions between the living and the materially dead through description of perceptions and practices that form the discursive space of the mortuary. PMID- 27269231 TI - Determining the Solar Inactivation Rate of BK Polyomavirus by Molecular Beacon. AB - The application of molecular beacons (MB) that bind to precise sequences of mRNA provides a near-universal approach in detecting evidence of viral replication. Here, we demonstrate the detection of BK Polyomavirus (BKPyV), an emerging indicator of microbiological water quality, by a quantum dot-based MB. The MB allowed us to rapidly characterize the inactivation rate of BKPyV following exposure to a solar simulator (kobs = 0.578 +/- 0.024 h(-1), R(2) = 0.92). Results were validated through a traditional cell-culture assay with immunofluorescence detection (kobs = 0.568 +/- 0.011 h(-1), R(2) = 0.97), which exhibited a strong correlation to MB data (R(2) = 0.93). Obtaining solar inactivation rates for BKPyV demonstrates the first use of a MB in characterizing a microbiological inactivation profile and helps assess the appropriateness of adopting BKPyV as an indicator organism for water quality. PMID- 27269232 TI - Survival and Prognostic Factors of Colorectal Liver Metastases After Surgical and Nonsurgical Treatment. AB - OBJECTIVE: Colorectal cancer is one leading cause of cancer-related death worldwide, and distant metastases determine an unfavorable prognosis. Surgical resection of colorectal liver metastases (CRLM) improves survival and provides the chance for cure. The aim of this study was to prospectively analyze the outcome of patients with CRLM in a population-based manner, and thereby, to compare the prognosis of patients undergoing resection with those receiving nonsurgical treatment. Moreover, we set out to identify and confirm important prognostic factors after resection of CRLM. PATIENTS AND METHODS: We analyzed the outcome of 506 patients diagnosed with CRLM in our institution from 1996 to 2011. Survival and the impact of clinical and pathologic factors were analyzed by univariate analysis. Important independent prognostic factors were analyzed by multivariate analysis. RESULTS: The 5-year overall survival rate (5y-OSR) for patients receiving resection of CRLM (n = 152) was 46% (95% confidence interval (CI), 37%-54%) compared with a 5y-OSR of 6% (95% CI, 4%-9%) for patients treated nonsurgically (n = 354). There was no perioperative mortality. Multivariate analysis revealed, among other factors, good performance status of the patient (low American Society of Anesthesiologists score), the absence of extrahepatic metastases, < 5 metastatic lesions, and a tumor-free resection margin (R0) as important, independent prognostic factors. Importantly, repeated hepatic resections of CRLM performed in 13 patients were associated with an excellent outcome (5y-OSR, 47%; 95% CI, 17%-72%). CONCLUSION: Surgical resection, which can be performed with tolerable site-effects, is the first choice for patients diagnosed with metachronous and synchronous CRLM. Of note, repeated resections should be advised in recurrent intrahepatic colorectal cancer whenever possible. PMID- 27269233 TI - Attitudes towards interprofessional collaboration among primary care physicians and nurses in Singapore. AB - Interprofessional collaboration (IPC) has been shown to improve patient outcomes, cost efficiency, and health professional satisfaction, and enhance healthy workplaces. We determined the attitudes of primary care physicians and nurses towards IPC and factors facilitating IPC using a cross-sectional study design in Singapore. A self-administered anonymous questionnaire, based on the Jefferson Scale of Attitudes toward Physician-Nurse Collaboration (JSAPNC), was distributed to primary healthcare physicians and nurses working in National Healthcare Group Polyclinics (N = 455). We found that the mean JSAPNC score for physicians was poorer than that for nurses (50.39 [SD = 4.67] vs. 51.61 [SD = 4.19], respectively, mean difference, MD = 1.22, CI = 0.35-2.09, p = .006). Nurses with advanced education had better mean JSAPNC score than nurses with basic education (52.28 [SD = 4.22] vs. 51.12 [SD = 4.11], respectively, MD = 1.16, CI = 0.12 2.20, p = .029). Male participants had poorer mean JSAPNC score compared to females (50.27 [SD = 5.02] vs. 51.38 [SD = 4.22], respectively MD = 1.11, CI = 0.07-2.14, p = .036). With regression analysis, only educational qualification among nurses was independently and positively associated with JSAPNC scores (p = .018). In conclusion, primary care nurses in Singapore had more positive attitudes towards IPC than physicians. Among nurses, those with advanced education had more positive attitudes than those with basic education. Greater emphasis on IPC education in training of physicians and nurses could help improve attitudes further. PMID- 27269235 TI - Tightening a loose loop of suture in a continuous laparoscopic suture line. PMID- 27269234 TI - Adverse impact of intermittent portal clamping on long-term postoperative outcomes in hepatocellular carcinoma. AB - Introduction To evaluate the impact of intermittent portal clamping (IPC) on long term postoperative outcomes in patients with hepatocellular carcinoma (HCC). Methods Clinical records of 355 patients underwent curative liver resection for HCC in January 2007 to December 2010 were retrospectively reviewed. According to how portal clamping was performed, patients were grouped as: IPC, n=113; other portal clamping (OPC), n=190; and no portal clamping (NPC), n=52. Results Median recurrence-free survival (RFS) was statistically significantly shorter in the IPC (39.4 months) than OPC (47.3 months, p=0.010) and NPC groups (51.4 months, p=0.008). Median overall survival (OS) was also significantly shorter with IPC (46.3 months), versus 52.9 months with OPC (p=0.022) and 56.2 months with NPC (p=0.015). Kaplan-Meier survival analysis revealed that 5-year cumulative RFS was much lower in the IPC (42.5%) than OPC (50.9%, p=0.014) and NPC groups (49.6%, p=0.013). Five-year cumulative OS was also much lower in the IPC (44.9%) than OPC (58.0%, p=0.020) and NPC groups (57.7%, p=0.025). On univariate analysis, tumour grade, size and number, TNM stage, blood transfusion, vascular invasion and IPC were significantly inversely correlated with RFS and OS. On multivariate analysis, tumour size and number, blood transfusion, vascular invasion and IPC remained significant. Conclusions Our study suggests that IPC is an independent risk factor for poor long-term postoperative outcomes in patients with HCC. PMID- 27269236 TI - The use of unicondylar cement spacers as a bone preserving measure in two-stage revision knee arthroplasty. PMID- 27269237 TI - A comparative audit of gunshot wounds and stab wounds to the neck in a South African metropolitan trauma service. AB - Introduction The aim of this comparative study of gunshot wounds (GSWs) and stab wounds (SWs) to the neck was to quantify the impact of the mechanism of injury on the outcome and management of penetrating neck injury (PNI). Methods A prospective trauma registry was interrogated retrospectively. Data were analysed pertaining to demographics and injury severity score (ISS), physiology on presentation, anatomical site of wounds and injuries sustained, investigations, management, outcome and complications. Results There were 452 SW and 58 GSW cases over the 46 months of the study. Patients with GSWs were more likely to have extracervical injuries than those with SWs (69% vs 63%). The incidence of a 'significant cervical injury' was almost twice as high in the GSW cohort (55% vs 31%). For patients with transcervical GSWs, this increased to 80%. The mean ISS was 17 for GSW and 11 for SW patients. Those in the GSW cohort presented with threatened airways and a requirement for an emergency airway three times as often as patients with SWs (24% vs 7% and 14% vs 5% respectively). The incidence among GSW and SW patients respectively was 5% and 6% for airway injuries, 12% and 8% for injuries to the digestive tract, 21% and 16% for vascular injuries, 59% and 10% for associated cervical injuries, 36% and 14% for maxillofacial injuries, 16% and 9% for injuries to the head, and 35% and 45% for injuries to the chest. In the GSW group, 91% underwent computed tomography angiography (CTA), with 23% of these being positive for a vascular injury. For SWs, 74% of patients underwent CTA, with 17% positive for a vascular injury. Slightly more patients with GSWs required operative intervention than those with SWs (29% vs 26%). Conclusions Patients with GSWs to the neck have a worse outcome than those with injuries secondary to SWs. However, the proportion of neck injuries actually requiring direct surgical intervention is not increased and most cases with PNI secondary to GSWs can be managed conservatively with a good outcome. Imaging should be performed for all GSWs to the neck. PMID- 27269238 TI - Avoiding fluid loss from an unused portal during hip arthroscopy. PMID- 27269239 TI - Surgery in the older person: Training needs for the provision of multidisciplinary care. AB - Introduction Many older surgical patients are exposed to high risks of morbidity and mortality when undergoing both elective and emergency surgery. Methods We provide an overview of perioperative care teams and the educational opportunities available to surgeons who undertake surgery in the older person. Findings The number of older people undergoing surgery is increasing at a rate faster than the proportion of older people in the overall population. Management of the older surgical patient throughout the surgical pathway forms part of the Specialty Training Curriculum for Geriatric Medicine. While 'surgery in childhood' continues to form part of the general surgical higher training syllabus, surgery in the later years of life does not. There are limited postgraduate courses and training opportunities currently available to surgeons in this field. There is clear societal need to address perioperative care for older surgical patients, which has proved successful in some centers. Moreover, surgical trainees support the inclusion of geriatric medicine issues into their training. Conclusions The ageing population requires a multidisciplinary perioperative approach, with dedicated and appropriately trained clinicians and allied health care professionals to improve outcomes. PMID- 27269240 TI - Hybrid tracheostomy. PMID- 27269241 TI - Modular emergency general surgery training: A pilot study of a novel programme. AB - Introduction Pan-speciality consensus guidance advocates mandatory emergency general surgery (EGS) training modules for specialist registrars (StRs). This pilot study evaluated the impact of EGS modules aimed at StRs over 1 year. Methods Eleven StRs were allocated a focused 4-week EGS module, in addition to the standard 1:12 on-call duty rota, in a tertiary surgical centre. Primary outcome measures included the number of indicative emergency operations and validated Procedure Based Assessments (PBAs) performed, both during the EGS module and over the training year. Results StRs performed a median of 11 (range 5 15) laparotomies during the EGS module versus 31 (range 9-49) over the whole training year. StRs attended 43.7% of available laparotomies during the module (range 24.1-63.7%). EGS modules provided more than one-third of the total emergency laparotomy experience, and a quarter of the emergency colectomy, appendicectomy and Hartmann's procedure experience. There were no differences in EGS module-related outcomes between junior and senior StRs. Significantly more PBAs related to laparotomy and segmental colectomy were completed during EGS modules than the on-call duty rota, at 32% versus 14% (p<0.001) and 48% versus 22% (p=0.019), respectively. Performance levels were maintained following module completion. Conclusions These findings provide an important baseline when considering future modular EGS training. PMID- 27269242 TI - A report on an acute, in-hours, outpatient review clinic with ultrasonography facilities for the early evaluation of general surgical patients. AB - Introduction In 2013 our hospital introduced an in-hours, consultant-led, outpatient acute surgical clinic (ASC) for emergency general surgical patients. In 2014 this clinic was equipped with a dedicated ultrasonography service. This prospective cohort study evaluated this service before and after the introduction of ultrasonography facilities. Methods Data were recorded prospectively for all patients attending the clinic during 2013 and 2014. The primary outcome was patient destination (whether there was follow-up/admission) after clinic attendance. Results The ASC reviewed patients with a wide age range and array of general surgical complaints. In 2013, 186 patients attended the ASC. After the introduction of the ultrasonography service in 2014, 304 patients attended. In 2014, there was a reduction in the proportion of patients admitted to hospital from the clinic (18.3% vs 8.9%, p=0.002). However, the proportion of patients discharged after ASC review remained comparable with 2013 (30.1% in 2013 vs 38.8% in 2014, p=0.051). The proportion of patients undergoing computed tomography (CT) scans also fell (14.0% vs 4.9%, p<0.001). Conclusions The ASC assessed a wide array of general surgical complaints. Only a small proportion required hospital admission. The introduction of an ultrasonography service was associated with a further reduction in admission rates and computed tomography. PMID- 27269243 TI - General paediatric surgery for patients aged under 5 years: a 5-year experience at a district general hospital. AB - Introduction The gradual shift of general paediatric surgery (GPS) provision from district general hospitals (DGH) to specialised units is well recognised in the UK. The consequences of centralisation include a reduction in exposure to GPS for current surgical trainees. The GPS practice of a DGH is examined here. Methods All operations performed on children aged under 5 years over a 5-year period were identified using the local electronic operation database. Electronic hospital records and clinic letters were accessed to collect data on demographics, operations performed and outcome measures. Results 472 GPS operations were performed on children between the age of 22 days and 5 years between 2009 and 2014, of which 43 were on an emergency basis and 105 were performed on patients aged less than 1 year. Three patients were admitted following day case surgery. Six patients were readmitted within 30 days. Complication rates for all procedures and the four most common procedures were similar to those found in published literature. Conclusions GPS for patients aged less than 5 years is comparatively safe in the DGH setting. The training opportunities available at DGHs are invaluable to surgical trainees and vital for sustaining the future provision of GPS by such hospitals. PMID- 27269244 TI - Multispectral Optoacoustic Tomography in Crohn's Disease: Noninvasive Imaging of Disease Activity. PMID- 27269246 TI - Common genetic variants in platelet surface receptors and its association with ischemic stroke. AB - Ischemic stroke has been named one of the leading causes of death worldwide. Whereas numerous biological mechanisms and molecules were found to be associated with stroke, platelets are particularly contributive to its pathogenesis. Recent data indicate considerable variability in platelet phenotype which accounts for differences in platelet surface receptor function, count and reactivity. These features collectively influence both the events leading to a disease and effectiveness of antiplatelet therapies. Consequently, genetic variants predisposing to cerebrovascular diseases can be sequenced using a wide array of techniques and become a useful tool in clinical setting. In this review, we provide an outline of common platelet polymorphisms that impose risk on ischemic stroke development and should be evaluated as targets to improve treatment. As study results are often inconsistent, partly due to differences in demographic characteristics between study populations and the fact that the functional impact of these variants has been relatively small, we conclude that both rare, low frequency and common variants might account for genetic contribution on abnormal platelet response to antiplatelet drugs. PMID- 27269247 TI - The Budget Impact of Increased Use of Febuxostat in the Management of Gout: A US Health Plan Managed Care Pharmacy and Medical Costs Perspective. AB - PURPOSE: Gout is a chronic disease characterized by the deposition of urate crystals in the joints and throughout the body, caused by an excess burden of serum uric acid (sUA). The study estimates pharmacy and medical cost budgetary impacts of wider adoption by US payers of febuxostat, a urate-lowering therapy (ULT) for the treatment of gout. METHODS: A US payer-perspective budget impact model followed ULT patients from a 1,000,000-member plan over 3 years. The current market share scenario, febuxostat (6%) and ULT allopurinol (94%), was compared with an 18% febuxostat market share. Data were implemented from randomized controlled trials, census and epidemiologic studies, and real-world database analyses. An innovation was the inclusion of gout-related chronic kidney disease costs. Cost results were estimated as annual and cumulative incremental costs, expressed as total costs, cost per member per month, and cost per treated member per month. Clinical results were also estimated. FINDINGS: Increasing the febuxostat market share resulted in a 6.3% increase in patients achieving the sUA target level of <6.0 mg/dL and a 1.4% reduction in gout flares during the 3-year period. Total cost increased 1.4%, with a 49.9% increase in ULT costs, a 1.4% reduction in flare costs, a 1.2% reduction in chronic kidney disease costs, and a 2.8% reduction in gout care costs. The cumulative incremental costs were $1,307,425 in the first year, $1,939,016 through the second year, and $2,092,744 through the third year. By the third year, savings in medical costs offset most of the increase in treatment costs. Impacts on cumulative cost per member per month and cumulative cost per treated member per month followed the same pattern, with the highest impact in the first year and cumulative impacts declining during the 3-year period. The cumulative cost per member per month impact was estimated as $0.109, $0.081, and $0.058 and the cumulative cost per treated member per month impact was estimated as $12.416, $9.207, and $6.625 in the first year, through the second year, and through the third year, respectively. IMPLICATIONS: Expanding the febuxostat market share would result in improved clinical outcomes, but with an overall increase in costs over 3 years due to higher costs of treatment. By the third year, savings in medical costs, primarily in chronic kidney disease costs, would offset most of the increase in treatment costs. Expanded use of febuxostat in the treatment of all gout patients, independent of renal impairment status, should be considered based on improved clinical outcomes and longer-term medical cost savings associated with these improved outcomes. PMID- 27269248 TI - A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development. AB - The modern drug discovery process involves multiple sources of high-dimensional data. This imposes the challenge of data integration. A typical example is the integration of chemical structure (fingerprint features), phenotypic bioactivity (bioassay read-outs) data for targets of interest, and transcriptomic (gene expression) data in early drug discovery to better understand the chemical and biological mechanisms of candidate drugs, and to facilitate early detection of safety issues prior to later and expensive phases of drug development cycles. In this paper, we discuss a joint model for the transcriptomic and the phenotypic variables conditioned on the chemical structure. This modeling approach can be used to uncover, for a given set of compounds, the association between gene expression and biological activity taking into account the influence of the chemical structure of the compound on both variables. The model allows to detect genes that are associated with the bioactivity data facilitating the identification of potential genomic biomarkers for compounds efficacy. In addition, the effect of every structural feature on both genes and pIC50 and their associations can be simultaneously investigated. Two oncology projects are used to illustrate the applicability and usefulness of the joint model to integrate multi-source high-dimensional information to aid drug discovery. PMID- 27269245 TI - Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer. AB - BACKGROUND & AIMS: The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects. METHODS: We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks. RESULTS: Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P < .001 and 1986-1992 vs 1984-1986; P < .002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC. CONCLUSIONS: Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer. PMID- 27269249 TI - Synthesis of a novel slow-release potassium fertilizer from modified Pidgeon magnesium slag by potassium carbonate. AB - A novel slow-release potassium fertilizer (SPF) was synthesized using Pidgeon magnesium slag (PMS) and potassium carbonate, which could minimize fertilizer nutrient loss and PMS disposal problems. Orthogonal experiments were conducted to determine the optimum conditions for synthesis. The potassium (K)-bearing compounds of SPF existed mainly in the form of crystalline phases Ca1.197K0.166SiO4, K2MgSiO4, and K4CaSi3O9, and in the noncrystalline phase. The active silicon content of SPF was 2.09 times as much as that of magnesium slag, and the slow-release character of SPF met the requirement for partly slow-release fertilizer in the national standard (GB/T23348-2009). The best models for describing the K release kinetics in water and 2% citric acid were the Elovich model and the first-order model, respectively. The heavy metal contents of SPF conformed to the national standard for organic-inorganic compound fertilizers, and the leaching mass concentrations of heavy metals and Fluorine were far lower than the limit values of the identification standard for hazardous waste identification for extraction toxicity (GB5085.3-2007), and also met the class II quality standard for ground water. The environmental risk of SPF is therefore very low, but because SPF is alkaline, its effect on soil pH should be taken into account. IMPLICATIONS: PMS is the solid waste resulting from the production of magnesium metal by Pidgeon's reduction process. Utilization of PMS in the high technology and high-value areas may promote the high-efficiency development of worldwide collection metallic magnesium industry and contribute to the reduction of emissions of fine dust to air. This paper presents one of the new techniques in the use of PMS as a slow-release fertilizer by adding K2CO3. The product can serve as a very cost-effective and reliable artificial fertilizer. PMID- 27269250 TI - De novo sequencing and transcriptome analysis of a low temperature tolerant Saccharum spontaneum clone IND 00-1037. AB - Saccharum spontaneum L., a wild relative of sugarcane, is known for its adaptability to environmental stresses, particularly cold stress. In the present study, an attempt was made for transcriptome profiling of the low temperature (10 degrees C) tolerant S. spontaneum clone IND 00-1037 collected from high altitude regions of Arunachal Pradesh, North Eastern India. The Illumina Nextseq500 platform yielded a total of 47.63 and 48.18 million reads corresponding to 4.7 and 4.8 gigabase pairs (Gb) of processed reads for control and cold stressed (10 degrees C for 24h) samples, respectively. These reads were de novo assembled into 214,611 unigenes with an average length of 801bp. Further, all unigenes were aligned to GO, KEGG and COG databases in order to identify novel genes and pathways responsive upon low temperature conditions. The differential gene expression analysis revealed that about 2583 genes were upregulated and 3302 genes were down regulated during the stress. This is perhaps the comprehensive transcriptome data of a low temperature tolerant clone of S. spontaneum. This study would aid in identifying novel genes and also in future genomic studies pertaining to sugarcane and its wild relatives. PMID- 27269251 TI - A Water-Soluble Cyclotriveratrylene-Based Supra-amphiphile: Synthesis, pH Responsive Self-Assembly in Water, and Its Application in Controlled Drug Release. AB - A new water-soluble cyclotriveratrylene (WCTV) was designed and synthesized, and benzyldimethyldodecylammonium chloride (G) was chosen as the guest molecule to construct a supra-amphiphile by the host-guest interaction between WCTV and G in water, which is pH responsive. The supra-amphiphiles self-assembled into vesicles in water. When the pH of the solution was below 7.0, the supra-amphiphile disassociated, and the vesicles collapsed. Then, the pH-responsive self-assembly system was utilized for controlled drug release. PMID- 27269252 TI - Esmolol attenuates lung injury and inflammation in severe acute pancreatitis rats. AB - BACKGROUND: Recent studies suggest that beta-adrenergic blockers attenuate systemic inflammation and improve survival in sepsis. We investigated whether esmolol can reduce lung injury and modulate inflammatory response in a rat model of severe acute pancreatitis (SAP). METHODS: A taurocholate-induced SAP was used, with or without continuously intravenous pumping of esmolol (15 mg/kg/h). Heart rate and arterial pressure were monitored. Nine hrs after esmolol administration, blood was drawn for blood gas analyses and cytokine (interleukin(IL)-6, tumor necrosis factor (TNF)-alpha) detections, lungs and pancreata were isolated for measurements of myeloperoxidase (MPO) activity and histological damage. In an additional 20 animals, rats were randomized into SAP or SAP + esmolol groups to assess effects of esmolol on survival time. RESULTS: Treatment with esmolol was associated with improved survival time (11.1 +/- 1.6 h vs. 9.2 +/- 2.0 h, p = 0.044) and less severe disease, as assessed by lung and pancreas histology. Blood gas analyses were ameliorated in esmolol group. Arterial PO2 increased (109.7 +/- 12.4 mmHg vs 93.9 +/- 4.1 mmHg, p = 0.008) while lactate levels (2.1 +/- 0.5 vs 3.1 +/- 0.7 mmol/L, p = 0.001) decreased in SAP + esmolol group as compared with SAP group. Esmolol treatment also abated the increase in bronchoalveolar lavage fluid protein and proinflammatory cytokines. Furthermore, esmolol reduced SAP induced plasma amylase activity (p = 0.02), blunted the expression of TNF-alpha (p = 0.003) and IL-6 (p < 0.001), and decreased pancreas/lung MPO activities. CONCLUSIONS: Continuous infusion of esmolol, a selective beta-1 adrenergic blocker, improves outcome, reduces inflammatory responses and also offers lung and pancreas protective effects in SAP rats. This may offer novel therapeutic strategies in treating patients suffering from SAP. PMID- 27269254 TI - Keratosis obturans complicated with facial nerve palsy: a diagnostic dilemma. PMID- 27269253 TI - Bilateral same-day endoscopic transcanal cartilage tympanoplasty: initial results. AB - INTRODUCTION: Same-day closure of bilateral tympanic membrane perforations is a quick and more comfortable procedure for the patients. However, conventional bilateral same-day tympanoplasty or myringoplasty has been rarely performed because of the theoretical risk of postoperative complications. OBJECTIVE: To evaluate the advantages and outcomes of bilateral simultaneous endoscopic cartilage tympanoplasty in patients with bilateral tympanic membrane perforations. METHODS: From February 2012 to March 2013, patients with bilateral dry tympanic membrane perforations who had some degree of hearing loss corresponding to the size and location of the perforation entered the study. There was no suspicion to disrupted ossicular chain, mastoid involvement or other middle or inner ear pathology. Endoscopic transcanal cartilage tympanoplasty was done using the underlay (medial) technique. The graft was harvested from cymba cartilage in just one ear with preservation of perichondrium in one side. A 1.5cm*1.5cm cartilage seemed to be enough for tympanoplasty in both sides. RESULTS: Nine patients (4 males and 5 females) with the mean age of 37.9 years underwent bilateral transcanal cartilage tympanoplasty in a same-day surgery. The mean duration of follow up was 15.8 months. There were detected no complications including hearing loss, otorrhea and wound complication with no retraction pocket or displaced graft during follow-up period. The grafts take rate was 94.44% (only one case of unilateral incomplete closure). The mean of air-bone gap overall improved from 13.88dB preoperatively to 9.16dB postoperatively (p<0.05). CONCLUSION: Bilateral endoscopic transcanal cartilage tympanoplasty can be considered as a safe minimally invasive procedure that can be performed in a same day surgery. It reduces the costs and operation time and is practical with a low rate of postoperative complications. PMID- 27269255 TI - The first investigative science-based evidence of Morgellons psychogenesis. AB - Morgellons disease is an infrequent syndromic condition, that typically affects middle-aged white women, characterized by crawling sensations on and under the skin, associated with itchy rashes, stinging sores, fiber-like filaments emerging from the sores, severe fatigue, concentrating difficulty, and memory loss. The scientific community is prone to believe that Morgellons is the manifestation of various psychiatric syndromes (Munchausen, Munchausen by proxy, Ekbom, Wittmaack Ekbom). Up until now, no investigative science-based evidence about its psychogenesis has ever been provided. In order to close this gap, we have analyzed the filaments extracted from the skin lesions of a 49-year-old Caucasian female patient, by using a Field Emission Gun-Environmental Electron Scanning Microscope equipped with an X-ray microprobe, for the chemico-elemental characterization of the filaments, comparing them with those collected during a detailed indoor investigation, with careful air monitoring, in her apartment. Our results prove the self-introduction under the epidermis of environmental filaments. For the first time in the literature, we have scientifically demonstrated the self-induced nature of Morgellons disease, thereby wiping out fanciful theories about its etiopathogenesis. PMID- 27269256 TI - Distinguishing the C3 vs SH4 Mass Split by Comprehensive Two-Dimensional Gas Chromatography-High Resolution Time-of-Flight Mass Spectrometry. AB - The C3 vs SH4 (0.0034 Da) mass split is considered to be one of the most critical mass splits in petroleomics and is relevant because of the regulatory requirements for sulfur in petroleum fractions. To date, there are two ways to resolve mass splits such as C3 vs SH4: (a) ultrahigh resolution Fourier transform mass spectrometry (FT-MS); (b) high-resolution chromatography such as comprehensive two-dimensional gas chromatography (GC*GC). High-resolution chromatography minimizes the mass spectral resolution required to distinguish these key chemical constituents and provides additional sample characterization via isomer separation. High resolution mass spectrometry enables unambiguous chemical formulas determination and structural elucidation. In this paper, we demonstrate the combination of high resolution GC*GC with high resolution time-of flight mass spectrometry to distinguish the C3 vs SH4 mass split and other common mass splits in a crude oil sample. PMID- 27269257 TI - Corrigendum to "Inhibition of serotonin reuptake in the prepubertal rat ovary by fluoxetine and effects on ovarian functions" [Reprod. Toxicol. 59 (2016) 80-88]. PMID- 27269258 TI - Introduction: Reappraising Paul Feyerabend. AB - This volume is devoted to a reappraisal of the philosophy of Paul Feyerabend. It has four aims. The first is to reassess his already well-known work from the 1960s and 1970s in light of contemporary developments in the history and philosophy of science. The second is to explore themes in his neglected later work, including recently published and previously unavailable writings. The third is to assess the contributions that Feyerabend can make to contemporary debate, on topics such as perspectivism, realism, and political philosophy of science. The fourth and final aim is to reconsider Feyerabend's place within the history of philosophy of science in the light of new scholarship. PMID- 27269259 TI - Historical antecedents to the philosophy of Paul Feyerabend. AB - Paul Feyerabend has been considered a very radical philosopher of science for proposing that we may advance hypotheses contrary to well-confirmed experimental results, that observations make theoretical assumptions, that all methodological rules have exceptions, that ordinary citizens may challenge the judgment of experts, and that human happiness should be a key value for science. As radical as these theses may sound, they all have historical antecedents. In defending the Copernican view, Galileo exemplified the first two; Mill, Aristotle and Machiavelli all argued for pluralism; Aristotle gave commonsense reasons for why ordinary citizens may be able to judge the work of experts; and a combination of Plato's and Aristotle's views can offer strong support for the connection between science and happiness. PMID- 27269260 TI - Rediscovering Einstein's legacy: How Einstein anticipates Kuhn and Feyerabend on the nature of science. AB - Thomas Kuhn and Paul Feyerabend promote incommensurability as a central component of their conflicting accounts of the nature of science. This paper argues that in so doing, they both develop Albert Einstein's views, albeit in different directions. Einstein describes scientific revolutions as conceptual replacements, not mere revisions, endorsing 'Kant-on-wheels' metaphysics in light of 'world change'. Einstein emphasizes underdetermination of theory by evidence, rational disagreement in theory choice, and the non-neutrality of empirical evidence. Einstein even uses the term 'incommensurable' specifically to apply to challenges posed to comparatively evaluating scientific theories in 1949, more than a decade before Kuhn and Feyerabend. This analysis shows how Einstein anticipates substantial components of Kuhn and Feyerabend's views, and suggests that there are strong reasons to suspect that Kuhn and Feyerabend were directly inspired by Einstein's use of the term 'incommensurable', as well as his more general methodological and philosophical reflections. PMID- 27269261 TI - Was Feyerabend a Popperian? Methodological issues in the History of the Philosophy of Science. AB - For more than three decades, there has been significant debate about the relation between Feyerabend and Popper. The discussion has been nurtured and complicated by the rift that opened up between the two and by the later Feyerabend's controversial portrayal of his earlier self. The first part of the paper provides an overview of the accounts of the relation that have been proposed over the years, disentangles the problems they deal with, and analyses the evidence supporting their conclusions as well as the methodological approaches used to process that evidence. Rather than advancing a further speculative account of the relation based on Feyerabend's philosophical work or autobiographical recollections, the second part of the paper strives to clarify the problems at issue by making use of a wider range of evidence. It outlines a historical reconstruction of the social context within which Feyerabend's intellectual trajectory developed, putting a special emphasis on the interplay between the perceived intellectual identity of Feyerabend, Feyerabend's own intellectual self concept, and the peculiar features of the evolving Popperian research group. PMID- 27269262 TI - Feyerabend's 'The concept of intelligibility in modern physics' (1948). AB - This essay introduces the transcription and translation of Paul Feyerabend's Der Begriff der Verstandlichkeit in der modernen Physik [The concept of intelligibility in modern physics] (1948), which is an early essay written by Paul Feyerabend in 1948 on the topic of intelligibility (Verstandlichkeit) and visualizability (Anschaulichkeit) of physical theories. The existence of such essay was likely. It is listed in his bibliography as his first publication. Yet the content of the essay was unknown, as no original or copy is extant in Feyerabend's Nachlass and no known published version was available to the community-until now. The essay has both historical and philosophical interest: it is, as far as our current knowledge goes, Feyerabend's earliest extant publication. It documents Feyerabend's philosophical interest as a physicist-to be, in what he himself called his "positivist" phase; and it gives a rare if fragmentary insight into the early discussions of the 'Third Vienna Circle' and, more generally, the philosophical culture of discussion in Vienna. PMID- 27269263 TI - The concept of intelligibility in modern physics (1948). AB - This is an English translation of Paul Feyerabend's earliest extant essay "Der Begriff der Verstandlichkeit in der modernen Physik" (1948). In it, Feyerabend defends positivism as a progressive framework for scientific research in certain stages of scientific development. He argues that in physics visualizability (Anschaulichkeit) and intelligibility (Verstandlichkeit) are time-conditioned concepts: what is deemed visualizable in the development of physical theories is relative to a specific historical context and changes over time. He concludes that from time to time the abandonment of visualizability is crucial for progress in physics, as it is conducive to major theory change, illustrating the point on the basis of advances in atomic theory. PMID- 27269264 TI - Der Begriff der Verstandlichkeit in der modernen Physik (1948). AB - This is a critical transcription of Paul Feyerabend's earliest extant essay "Der Begriff der Verstandlichkeit in der modernen Physik" (1948) recovered from the European Forum Alpbach archives. In it, Feyerabend defends positivism as a progressive framework for scientific research in certain stages of scientific development. He argues that in physics visualizability (Anschaulichkeit) and intelligibility (Verstandlichkeit) are time-conditioned concepts: what is deemed visualizable in the development of physical theories is relative to a specific historical context and changes over time. He concludes that from time to time the abandonment of visualizability is crucial for progress in physics, as it is conducive to major theory change, illustrating the point on the basis of advances in atomic theory. PMID- 27269265 TI - Reasons for relativism: Feyerabend on the 'Rise of Rationalism' in ancient Greece. AB - This paper argues that essential features of Feyerabend's philosophy, namely his radicalization of critical rationalism and his turn to relativism, could be understood better in the light of his engagement with early Greek thought. In contrast to his earlier, Popperian views he came to see the Homeric worldview as a genuine alternative, which was not falsified by the Presocratics. Unlike socio psychological and externalist accounts my reading of his published and unpublished material suggests that his alternative reconstruction of the ancient beginnings of the Western scientific tradition motivate and justify his moderate Protagorean relativism. PMID- 27269266 TI - The rise of western rationalism: Paul Feyerabend's story. AB - I summarize certain aspects of Paul Feyerabend's account of the development of Western rationalism, show the ways in which that account is supposed to run up against an alternative, that of Karl Popper, and then try to give a preliminary comparison of the two. My interest is primarily in whether what Feyerabend called his 'story' constitutes a possible history of our epistemic concepts and their trajectory. I express some grave reservations about that story, and about Feyerabend's framework, finding Popper's views less problematic here. However, I also suggest that one important aspect of Feyerabend's material, his treatment of religious belief, can be given an interpretation which makes it tenable, and perhaps preferable to a Popperian approach. PMID- 27269267 TI - Feyerabend, truth, and relativisms: Footnotes to the Italian debate. AB - There is a substantial literature on Feyerabend's relativism-including a few papers in this collection-but fewer specific studies of the ways that his writings and ideas have been taken up among the non-academic public. This is odd, given his obvious interest in the lives and concerns of persons who were not 'intellectuals'-a term that, for him, had a pejorative ring to it. It is also odd, given the abundance of evidence of how Feyerabend's relativism played a role in a specific national and cultural context-namely, contemporary Italian debates about relativism. This paper offers a study of how Feyerabend's ideas have been deployed by Italian intellectuals and cultural commentators-including the current Pope-and critically assesses them. PMID- 27269268 TI - Between relativism and pluralism: Philosophical and political relativism in Feyerabend's late work. AB - Relativism is one of the most problematic terms associated with philosophical discourse, with Feyerabend considered among the most important twentieth century theorists subscribing to it. This paper provides a detailed overview of relativist positions advanced in Feyerabend's mid-to-late work and investigates the associated epistemic and political applications. Emphasis is placed on how Feyerabend supported certain aspects of relativism, and at what stage he rejected others. It is noted that Feyerabend had already imposed limitations on relativism in Farewell to Reason, in which he entertained the possibility of epistemic definition within stable contexts, and advanced the notion that opportunities and equality associated with political and cultural units could only be valid within a democratic system. In Conquest of Abundance, political relativism is largely discarded, while epistemological relativism is increasingly treated as an appeal for diversity in all areas. In this re-reading of his work, it becomes clear that Feyerabend was already advocating a moderate form of epistemic and political relativism in the middle of his career, which he subsequently developed in the direction of "ontological pluralism" in his later work. This paper thus shows that Feyerabend's relativism should not be completely rejected, but rather that it continues to offer interesting food for thought. PMID- 27269269 TI - Relativism in Feyerabend's later writings. AB - This paper reconstructs, and distinguishes between, Feyerabend's different forms of relativism in his later writings. Science in a Free Society remains close to familiar forms of relativism, while, at the same time, developing an original but under-argued form of political relativism, and rejecting "conversion" models of cultural exchange. Farewell to Reason moves away from common renderings of relativism, and develops a range of different new forms. Central here are links between relativism, skepticism and infallibilism. In the last six years of his life, Feyerabend often criticizes a peculiar radical form of relativism that arguably no-one has ever proposed or defended. In the same context, Feyerabend sketches an "ontological" form of relativism. It combines "Kantian humility", metaphysical pluralism and constructivism. PMID- 27269270 TI - Challenging Expertise: Paul Feyerabend vs. Harry Collins & Robert Evans on democracy, public participation and scientific authority: Paul Feyerabend vs. Harry Collins & Robert Evans on scientific authority and public participation. AB - This paper compares Feyerabend's arguments in Science in a Free Society to the controversial theory of expertise proposed by Harry Collins and Robert Evans as a Third Wave of Science Studies. Is the legitimacy of democratic decisions threatened by the unquestioned authority of scientific advice? Or does, on the contrary, science need protection from too much democratic participation in technical decisions? Where Feyerabend's political relativism envisions democratic society as inherently pluralist and demands equal contribution of all traditions and worldviews to public decision-making, Collins and Evans hold a conception of elective modernism, defending the reality and value of technical expertise and arguing that science deserves a privileged status in modern democracies, because scientific values are also democratic values. I will argue that Feyerabend's political relativism provides a valuable framework for the evaluation of Collins' and Evans' theory of expertise. By constructing a dialog between Feyerabend and this more recent approach in Science and Technology Studies, the aim of this article is not only to show where the two positions differ and in what way they might be reconciled, but also how Feyerabend's philosophy provides substantial input to contemporary debate. PMID- 27269271 TI - Feyerabend on politics, education, and scientific culture. AB - The purpose of this paper is to offer a sympathetic reconstruction of the political thought of Paul Feyerabend. Using a critical discussion of the idea of the 'free society' it is suggested that his political thought is best understood in terms of three thematic concerns-liberation, hegemony, and the authority of science-and that the political significance of those claims become clear when they are considered in the context of his educational views. It emerges that Feyerabend is best understood as calling for the grounding of cognitive and cultural authorities-like the sciences-in informed deliberation, rather than the uncritical embrace of prevailing convictions. It therefore emerges that a free society is best understood as one of epistemically responsible citizenship rather than epistemically anarchistic relativism of the 'anything goes' sort-a striking anticipation of current debates about philosophy of science in society. PMID- 27269272 TI - Late Feyerabend on materialism, mysticism, and religion. AB - Feyerabend's interests in religion and mysticism grew through his career. In his later writings, Feyerabend's numerous critiques of scientific materialism are often accompanied by purported advantages of religious orientations and temperaments. These recommendations do not simply follow from his tolerant theoretical pluralism; they are more positive attempts to articulate distinctive aspects of human life satisfied by religion, but not by scientific materialism. Elevating the human need for mystery, reverence, and love, he contrasts these goods with the deliverances of monistic conceptions of science and reason. I bring attention to some of the common themes in these remarks to argue that they were integral with other parts of his philosophical project and that they could serve as helpful rejoinders to contemporary exhortations to science-based secularism from philosophers of science. PMID- 27269273 TI - Feyerabend's perspectivism. AB - Although, Feyerabend himself seems never to have used the term 'perspectivism' to designate a philosophical position, I think his views about science are very well characterized as perspectival. In fact, his later writings contain much that contributes to current thinking about perspectivism. I would like, therefore, to distinguish my own perspectivism from Feyerabend's. In the end, I will argue, his perspectivism is lacking enough of the critical bite that the younger Feyerabend found so attractive in Popper's philosophy. PMID- 27269274 TI - The abundant world: Paul Feyerabend's metaphysics of science. AB - The goal of this paper is to provide an interpretation of Feyerabend's metaphysics of science as found in late works like Conquest of Abundance and Tyranny of Science. Feyerabend's late metaphysics consists of an attempt to criticize and provide a systematic alternative to traditional scientific realism, a package of views he sometimes referred to as "scientific materialism." Scientific materialism is objectionable not only on metaphysical grounds, nor because it provides a poor ground for understanding science, but because it implies problematic claims about the epistemic and cultural authority of science, claims incompatible with situating science properly in democratic societies. I show how Feyerabend's metaphysical view, which I call "the abundant world" or "abundant realism," constitute a sophisticated and challenging form of ontological pluralism that makes interesting connections with contemporary philosophy of science and issues of the political and policy role of science in a democratic society. PMID- 27269275 TI - Acceptance of technology-based tools in a sample of Parkinson's patients. AB - Objectives Parkinson's disease is the second most common neurodegenerative movement disorder in the United States. Patients' opinions of technology-based tools for education and communication as related to Parkinson's disease are unclear with little documented research addressing the issue. The goal of this research was to investigate patient opinions about technology-based tools with a focus on differences between patients of different age groups. Methods A cross sectional survey was used to assess views on using multiple different electronic methods for receiving instructions and communicating with healthcare providers in 109 Parkinson's disease patients. Results Approximately 28% (n = 28) of the subjects reported having unmet needs related to Parkinson's disease. Those 65 and over were less likely to believe that using technology to communicate with the healthcare center would result in themselves having a better understanding of their care (odds ratio = 0.36, 95% confidence interval: 0.14, 0.95). Those over 75 had a lower odds of being willing to use electronic methods (odds ratio = 0.33, 95% confidence interval: 0.14, 0.79), a lower odds of believing that technology would result in better self-understanding of medical needs (odds ratio = 0.27, 95% confidence interval: 0.12, 0.63) and a lower odds of believing that technology would result in their healthcare providers better understanding their needs (odds ratio = 0.32, 95% confidence interval: 0.14, 0.73). Discussion The results of this study indicate that older Parkinson's disease patients report a less favorable view regarding the role of technology in communicating with healthcare providers and for understanding their care. PMID- 27269276 TI - Lisinopril-Induced Alopecia: A Case Report. AB - The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines consider angiotensin-converting enzyme (ACE) inhibitors as one of the mainstay therapies in the management of heart failure. The widespread use of ACE inhibitors has been associated with several notable adverse effects such as hyperkalemia and an increased serum creatinine. There are no previous reports of alopecia associated with lisinopril use; however, a few previous cases of alopecia associated with other ACE inhibitors exist. This report discusses a case of lisinopril-induced alopecia of a 53-year-old male presenting to our outpatient heart failure clinic with a chief complaint of a new onset of alopecia. Upon evaluation, it was suspected that the patient's alopecia was likely medication induced by lisinopril; therefore, lisinopril was discontinued and switched to an angiotensin receptor blocker (ARB), losartan potassium. Alopecia resolved in 4 weeks after the therapeutic intervention. Our report suggests that the patient likely experienced a medication-induced alopecia, which was successfully resolved through proper identification and removal of the causative agent. Causality assessment between lisinopril and alopecia was determined using the Naranjo Adverse Drug Reaction Probability Scale-a total score of 6 was achieved and thus identified the adverse drug reaction as probable. Clinicians should be aware of the possibility that lisinopril may be an offending agent in a patient with unexplained alopecia. PMID- 27269277 TI - Use of the My Health Record by people with communication disability in Australia: A review to inform the design and direction of future research. AB - BACKGROUND: People with communication disability often struggle to convey their health information to multiple service providers and are at increased risk of adverse health outcomes related to the poor exchange of health information. OBJECTIVE: The purpose of this article was to (a) review the literature informing future research on the Australian personally controlled electronic health record, 'My Health Record' (MyHR), specifically to include people with communication disability and their family members or service providers, and (b) to propose a range of suitable methodologies that might be applied in research to inform training, policy and practice in relation to supporting people with communication disability and their representatives to engage in using MyHR. METHOD: The authors reviewed the literature and, with a cross-disciplinary perspective, considered ways to apply sociotechnical, health informatics, and inclusive methodologies to research on MyHR use by adults with communication disability. RESEARCH OUTCOMES: This article outlines a range of research methods suitable for investigating the use of MyHR by people who have communication disability associated with a range of acquired or lifelong health conditions, and their family members, and direct support workers. CONCLUSION: In planning the allocation of funds towards the health and well-being of adults with disabilities, both disability and health service providers must consider the supports needed for people with communication disability to use MyHR. There is an urgent need to focus research efforts on MyHR in populations with communication disability, who struggle to communicate their health information across multiple health and disability service providers. The design of studies and priorities for future research should be set in consultation with people with communication disability and their representatives. PMID- 27269278 TI - Modeling Clustered Data with Very Few Clusters. AB - Small-sample inference with clustered data has received increased attention recently in the methodological literature, with several simulation studies being presented on the small-sample behavior of many methods. However, nearly all previous studies focus on a single class of methods (e.g., only multilevel models, only corrections to sandwich estimators), and the differential performance of various methods that can be implemented to accommodate clustered data with very few clusters is largely unknown, potentially due to the rigid disciplinary preferences. Furthermore, a majority of these studies focus on scenarios with 15 or more clusters and feature unrealistically simple data generation models with very few predictors. This article, motivated by an applied educational psychology cluster randomized trial, presents a simulation study that simultaneously addresses the extreme small sample and differential performance (estimation bias, Type I error rates, and relative power) of 12 methods to account for clustered data with a model that features a more realistic number of predictors. The motivating data are then modeled with each method, and results are compared. Results show that generalized estimating equations perform poorly; the choice of Bayesian prior distributions affects performance; and fixed effect models perform quite well. Limitations and implications for applications are also discussed. PMID- 27269280 TI - Aneuploidies level in sperm nuclei in patients with infertility. AB - Male infertility is a relevant social and medical problem. Male infertility is mostly caused by genetic disorders. The purpose of the study was to analyze the correlation of chromosome aberrations, as well as DNA fragmentation and various manifestations of spermatogenesis disorder. Sperm samples of 58 males with infertility and 23 conditionally healthy males were studied. All patients diagnosed with asthenozoospermia, teratozoospermia, oligoasthenozoospermia and oligoteratozoospermia underwent subsequent analysis of sperm DNA fragmentation. Sperm DNA fragmentation was examined with sperm chromatin dispersion test (sperm chromatin dispersion, Spermprocessor, India) with an Axioscope 40 fluorescent microscope. Fluorescence in situ hybridization with fluorescent probes (Vysis Multi Vysion PGT, Abbot Molecular) was used to study chromosome abnormalities in sperm nuclei with regard to X and Y chromosomes, as well as to chromosomes 18 and 21. It was found that the development of pathospermia was characterized by genetic discontinuity, which manifests as DNA fragmentation and disjunction of chromosomes in meiosis with spermatogenesis. It was also found that the prevailing type of pathospermia in men with infertility was oligozoospermia. In addition, this group also had the highest rate of numerical chromosome abnormalities. This was caused by the degeneration of spermatozoids with aneuploidies in chromosomes. PMID- 27269279 TI - Efficacy of Bevacizumab Compared to Mitomycin C Modulated Trabeculectomy in Primary Open Angle Glaucoma: A One-Year Prospective Randomized Controlled Study. AB - PURPOSE: To compare the efficacy of bevacizumab over mitomycin C (MMC) modulated trabeculectomy in cases of primary open angle glaucoma (POAG). METHOD: In this prospective randomized controlled study, 80 eyes of 80 patients with uncontrolled POAG or intolerant to antiglaucoma medications were randomized to two groups: Group 1 (n = 40) patients underwent trabeculectomy modulated with MMC (0.2 mg/ml), whereas Group 2 (n = 40) patients underwent trabeculectomy modulated with bevacizumab (1.25 mg/0.05 ml). The outcome measures were best corrected visual acuity (BCVA), intraocular pressure (IOP), number of glaucoma medications and bleb morphological features based on Moorfields Bleb Grading System (MBGS). All patients were followed up for one year post trabeculectomy. RESULTS: The mean preoperative IOP in the bevacizumab group improved from 22.41 +/-1.08 mm Hg with 3.2 +/- 0.9 glaucoma medications to 13.68 +/- 0.79 mm Hg with 0.11 +/- 0.32 glaucoma medications at one year (P < 0.001). The mean preoperative IOP in the MMC group improved from 22.64 +/- 0.90 mm Hg with 3.1 +/- 0.8 glaucoma medications to 13.84 +/- 0.73 mm Hg with 0.17 +/- 0.38 glaucoma medications at one year (P < 0.001). IOP was comparable between two groups at one year (P = 0.43). No significant differences were found in bleb morphological features based on MBGS regarding central bleb area, peripheral bleb area, height and central vascularity between the two groups at six months and one year. However, there was a statistically significant difference in peripheral bleb vascularity and peripheral non-bleb vascularity with bevacizumab group exhibiting a low degree of vascularity at one year (P = 0.029 and 0.004, respectively). CONCLUSION: Adjunctive bevacizumab in trabeculectomy is effective and comparable to MMC for controlling IOP in POAG patients for the first year. PMID- 27269281 TI - Detection of Chlamydiales DNA in questing ticks. PMID- 27269282 TI - Factors that affect stabilisation times of canine spontaneous hypoadrenocorticism. AB - The objective of this retrospective study was to examine factors that may have affected the stabilisation times of 50 dogs with spontaneous hypoadrenocorticism that were being treated with fludrocortisone acetate, with particular emphasis on dosing frequency and the concurrent use of prednisolone. Stabilisation was defined as an absence of clinical signs with a sodium:potassium ratio >27:1 and both electrolyte concentrations within a laboratory reference range. It was found that the median time till stabilisation was three months. The frequency of fludrocortisone treatment (once, twice or changed from once to twice a day) had no effect on the stabilisation time. The two groups of dogs that were started and stabilised on once a day or twice a day dosing had a median stabilisation time of two months. However, dogs that failed to stabilise on once a day dosing of fludrocortisone and were then changed onto twice a day dosing then stabilised a median of one month later. Concurrent use of prednisolone resulted in significantly faster stabilisation times. It was concluded that dogs with hypoadrenocorticism should be continued on prednisolone therapy until they are stabilised. If a dog is failing to stabilise on once a day fludrocortisone acetate, a change to twice a day administration could be considered. PMID- 27269283 TI - Pentagone internalises glypicans to fine-tune multiple signalling pathways. AB - Tight regulation of signalling activity is crucial for proper tissue patterning and growth. Here we investigate the function of Pentagone (Pent), a secreted protein that acts in a regulatory feedback during establishment and maintenance of BMP/Dpp morphogen signalling during Drosophila wing development. We show that Pent internalises the Dpp co-receptors, the glypicans Dally and Dally-like protein (Dlp), and propose that this internalisation is important in the establishment of a long range Dpp gradient. Pent-induced endocytosis and degradation of glypicans requires dynamin- and Rab5, but not clathrin or active BMP signalling. Thus, Pent modifies the ability of cells to trap and transduce BMP by fine-tuning the levels of the BMP reception system at the plasma membrane. In addition, and in accordance with the role of glypicans in multiple signalling pathways, we establish a requirement of Pent for Wg signalling. Our data propose a novel mechanism by which morphogen signalling is regulated. PMID- 27269284 TI - Nucleosome disassembly during human non-homologous end joining followed by concerted HIRA- and CAF-1-dependent reassembly. AB - The cell achieves DNA double-strand break (DSB) repair in the context of chromatin structure. However, the mechanisms used to expose DSBs to the repair machinery and to restore the chromatin organization after repair remain elusive. Here we show that induction of a DSB in human cells causes local nucleosome disassembly, apparently independently from DNA end resection. This efficient removal of histone H3 from the genome during non-homologous end joining was promoted by both ATM and the ATP-dependent nucleosome remodeler INO80. Chromatin reassembly during DSB repair was dependent on the HIRA histone chaperone that is specific to the replication-independent histone variant H3.3 and on CAF-1 that is specific to the replication-dependent canonical histones H3.1/H3.2. Our data suggest that the epigenetic information is re-established after DSB repair by the concerted and interdependent action of replication-independent and replication dependent chromatin assembly pathways. PMID- 27269285 TI - Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice. AB - We discovered that optical stimulation of the mystacial pad in Emx1-Cre;Ai27D transgenic mice induces whisker movements due to activation of ChR2 expressed in muscles controlling retraction and protraction. Using high-speed videography in anesthetized mice, we characterize the amplitude of whisker protractions evoked by varying the intensity, duration, and frequency of optogenetic stimulation. Recordings from primary somatosensory cortex (S1) in anesthetized mice indicated that optogenetic whisker pad stimulation evokes robust yet longer latency responses than mechanical whisker stimulation. In head-fixed mice trained to report optogenetic whisker pad stimulation, psychometric curves showed similar dependence on stimulus duration as evoked whisker movements and S1 activity. Furthermore, optogenetic stimulation of S1 in expert mice was sufficient to substitute for peripheral stimulation. We conclude that whisker protractions evoked by optogenetic activation of whisker pad muscles results in cortical activity and sensory perception, consistent with the coding of evoked whisker movements by reafferent sensory input. PMID- 27269288 TI - "Their Today Is Our Future": Direct Carers' Work Experience and Formal Caring Relationships in a Community-Based Eldercare Program in Shanghai. AB - The purpose of this study is to explore direct carers' work experience and formal caring relationships with older adults in a community-based eldercare program in Shanghai. Existing evidence has primarily focused on direct carers' work experience in residential care settings. However, direct carers' experiences of caring older adults in the community also deserve exploration. This qualitative study purposively sampled direct carers who worked in government-sponsored programs. Carers participated in semi-structured, in-depth interviews ( N = 37). Results reveal that despite occasional frustration, direct carers undertook demanding workloads and fostered strong emotional attachments with older adult clients. "Karma" was a critical cultural factor pertaining to their work ethic and motivated their care provision to benefit their future elderly selves. This study recognizes the cultural aspects of caring relationships that contribute to the quality of care of the community-based older adults in urban China. PMID- 27269286 TI - Golgi self-correction generates bioequivalent glycans to preserve cellular homeostasis. AB - Essential biological systems employ self-correcting mechanisms to maintain cellular homeostasis. Mammalian cell function is dynamically regulated by the interaction of cell surface galectins with branched N-glycans. Here we report that N-glycan branching deficiency triggers the Golgi to generate bioequivalent N glycans that preserve galectin-glycoprotein interactions and cellular homeostasis. Galectins bind N-acetyllactosamine (LacNAc) units within N-glycans initiated from UDP-GlcNAc by the medial-Golgi branching enzymes as well as the trans-Golgi poly-LacNAc extension enzyme beta1,3-N-acetylglucosaminyltransferase (B3GNT). Marginally reducing LacNAc content by limiting N-glycans to three branches results in T-cell hyperactivity and autoimmunity; yet further restricting branching does not produce a more hyperactive state. Rather, new poly LacNAc extension by B3GNT maintains galectin binding and immune homeostasis. Poly LacNAc extension is triggered by redistribution of unused UDP-GlcNAc from the medial to trans-Golgi via inter-cisternal tubules. These data demonstrate the functional equivalency of structurally dissimilar N-glycans and suggest a self correcting feature of the Golgi that sustains cellular homeostasis. PMID- 27269289 TI - Perceived Benefits, Barriers, and Drivers of Telemedicine From the Perspective of Skilled Nursing Facility Administrative Staff Stakeholders. AB - Potentially avoidable hospitalizations (PAHs) of skilled nursing facility (SNF) patients are common and costly. Telemedicine represents a unique approach to manage and potentially reduce PAHs in SNFs, having been used in a variety of settings to improve coordination of care and enhance access to providers. Nonetheless, broad implementation and use of telemedicine lags in SNFs relative to other health care settings. To understand why, we surveyed SNF administrative staff attending a 1-day telemedicine summit. Participants saw the highest value of telemedicine in improving the quality of care and reducing readmissions. They identified hospital and managed care telemedicine requirements as primary drivers of adoption. The most significant barrier to adoption was the initial investment required. A joint research-policy effort to improve the evidence base around telemedicine in SNFs and introduce incentives may improve adoption and continued use of telemedicine in this setting. PMID- 27269290 TI - Comparing Effects of Intrinsic and Extrinsic Social Values Between Younger and Older Employees. AB - Socioemotional selectivity theory proposes that older adults emphasize emotional goals and interpersonal closeness to a greater extent than do younger adults, suggesting that holding social work-related values (SWVs) may be beneficial to older employees. This project aimed at examining two dimensions of SWVs, intrinsic and extrinsic SWVs, and tested whether age and work situation would moderate their effects on self-rated job performance. A cross-sectional survey (Study 1, N = 357) and a 14-day experience sampling study (Study 2, N = 77) were conducted among Chinese managerial employees. Study 1 showed that the direct effect of intrinsic SWVs on self-rated job performance was stronger in older employees than in younger employees. Study 2 demonstrated that older employees who valued intrinsic SWVs while being in social situations performed much better than when they did not value intrinsic SWVs but being in social situations; however such positive effect was not shown in younger employees. Findings of this project reveal that the effect of SWVs varies across locus of effect (intrinsic versus extrinsic), age, and work situation. Among older employees, the positive effect of intrinsic SWVs is more crucial than that of extrinsic SWVs on self rated job performance. Findings of this project imply that intrinsically rewarding incentives would be more effective in motivating older employees to reach peak performance. PMID- 27269287 TI - Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling. AB - Integrin dependent regulation of growth factor signalling confers anchorage dependence that is deregulated in cancers. Downstream of integrins and oncogenic Ras the small GTPase Ral is a vital mediator of adhesion dependent trafficking and signalling. This study identifies a novel regulatory crosstalk between Ral and Arf6 that controls Ral function in cells. In re-adherent mouse fibroblasts (MEFs) integrin dependent activation of RalA drives Arf6 activation. Independent of adhesion constitutively active RalA and RalB could both however activate Arf6. This is further conserved in oncogenic H-Ras containing bladder cancer T24 cells, which express anchorage independent active Ral that supports Arf6 activation. Arf6 mediates active Ral-exocyst dependent delivery of raft microdomains to the plasma membrane that supports anchorage independent growth signalling. Accordingly in T24 cells the RalB-Arf6 crosstalk is seen to preferentially regulate anchorage independent Erk signalling. Active Ral we further find uses a Ral-RalBP1-ARNO-Arf6 pathway to mediate Arf6 activation. This study hence identifies Arf6, through this regulatory crosstalk, to be a key downstream mediator of Ral isoform function along adhesion dependent pathways in normal and cancer cells. PMID- 27269291 TI - Impulsivity, working memory, and impaired control over alcohol: A latent variable analysis. AB - Impaired control over alcohol is an important risk factor for heavy drinking among young adults and may mediate, in part, the association between personality risk and alcohol problems. Research suggests that trait impulsivity is associated with impaired control over alcohol; however, few studies of this association have included a range of impulsivity facets. The purpose of this study was to examine specific pathways from higher order impulsivity factors to alcohol problems mediated via impaired control over alcohol. We also examined the moderating role of working memory in these associations. Young heavy drinkers (N = 300) completed 2 multidimensional impulsivity measures along with self-report measures of impaired control over alcohol, alcohol use, and alcohol problems. Working memory was assessed using a computerized digit span task. Results showed that the impulsivity facets loaded onto 2 higher order factors that were labeled Response and Reflection Impulsivity. Response impulsivity predicted unique variance in self-reported impaired control and alcohol problems, whereas reflection impulsivity predicted unique variance in heavy drinking frequency only. Further, significant indirect associations were observed from response and reflection impulsivity to alcohol problems mediated via impaired control and heavy drinking frequency, respectively. Working memory and sensation seeking were not uniquely associated with the alcohol variables, and no support was found for the moderating role of working memory. The results help to clarify associations among impulsivity, impaired control, and alcohol problems, suggesting that impaired control may play a specific role in the pathway to alcohol problems from response impulsivity but not from reflection impulsivity. (PsycINFO Database Record PMID- 27269292 TI - Contextual influences on early drinking: Characteristics of drinking and nondrinking days. AB - Research characterizing the adolescent drinking context is limited, often relies on samples of current drinkers reporting on recent/last or typical drinking experiences, and provides little information about the context of very early use. The present study uses repeated monthly assessments to describe the context of drinking days and matched nondrinking days to determine the unique risk associated with different drinking-related characteristics. Additionally, we used latent class analysis to empirically identify key configurations of drinking related characteristics and both family- and nonfamily-related environmental characteristics (social context, physical location, source of alcohol). Data included 688 days (344 drinking days, 344 nondrinking days) from 164 middle school students enrolled in a prospective study on drinking initiation and progression (62% female; 26% non-White, 11% Hispanic). Results supported 4 patterns: (a) heavier drinking occurring in a peer context, lighter drinking occurring in (b) a family context or (c) a peer context, and (d) drinking alcohol obtained at home without permission. Latent classes varied as a function of gender, age, peer norms, and parenting behaviors as well as alcohol type and perceived alcohol availability. Findings indicated that highly endorsed contexts were not necessarily the riskiest ones, and simply targeting an oft-reported source of alcohol, physical location, or social context may not be an effective strategy for reducing underage drinking. Additionally, although greater monitoring and anticipated parent reaction to drinking are typically protective against adolescent drinking, we found they were associated with parent-sanctioned drinking, suggesting the role of parenting practices must be considered in the context of drinking pattern. (PsycINFO Database Record PMID- 27269293 TI - A population-based study of help seeking and self-medication among trauma-exposed individuals. AB - Epidemiologic studies of trauma highlight the imbalance between prevalence of psychiatric diagnoses and help seeking. We investigated prevalence and correlates of help seeking and self-medication in Norwegian adults with trauma history with a focus on common posttrauma outcomes of posttraumatic stress disorder (PTSD) and substance use disorders (alcohol or drug). Participants reporting at least 1 PTSD symptom (n = 307) were asked if they consulted with a doctor/another professional (help seeking) or used drugs/alcohol (self-medication) for trauma-related problems. PTSD, alcohol abuse or dependence (AUD), and drug use or dependence (DUD) were assessed via structured diagnostic interviews. Help seeking and self medication were endorsed by 37.4% and 10.4% of the sample, respectively. As compared to the full sample, help seeking was endorsed at a greater rate in individuals with PTSD (chi2 = 8.59, p = .005) and at a lower rate in those with AUD (chi2 = 7.34, p < .004). Self-medication was more likely to be endorsed by individuals with PTSD than without PTSD (chi2 = 25.68, p < .001). In regression analyses, PTSD was associated with increased likelihood of self-medication (odds ratio [OR] = 4.56) and help seeking (OR = 2.29), while AUD was associated with decreased likelihood of help-seeking (OR = .29). When self-medication was included as a predictor, PTSD was no longer associated with help seeking, although AUD remained inversely associated. PTSD and AUDs have a nuanced relationship with formal help seeking as well as the use of substances to cope. Trauma-exposed individuals are likely engaging in adaptive and maladaptive coping strategies, the latter of which may be compounding distress. (PsycINFO Database Record PMID- 27269294 TI - Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. AB - OBJECTIVES: To evaluate the safety and tolerability of the intravenous administration of Cx611, a preparation of allogeneic expanded adipose-derived stem cells (eASCs), in patients with refractory rheumatoid arthritis (RA), as well as to obtain preliminary clinical efficacy data in this population. METHODS: It is a multicentre, dose escalation, randomised, single-blind (double-blind for efficacy), placebo-controlled, phase Ib/IIa clinical trial. Patients with active refractory RA (failure to at least two biologicals) were randomised to receive three intravenous infusions of Cx611: 1 million/kg (cohort A), 2 million/kg (cohort B), 4 million/kg (cohort C) or placebo, on days 1, 8 and 15, and they were followed for therapy assessment for 24 weeks. RESULTS: Fifty-three patients were treated (20 in cohort A, 20 in cohort B, 6 in cohort C and 7 in placebo group). A total of 141 adverse events (AEs) were reported. Seventeen patients from the group A (85%), 15 from the group B (75%), 6 from the group C (100%) and 4 from the placebo group (57%) experienced at least one AE.Eight AEs from 6 patients were grade 3 in intensity (severe), 5 in cohort A (lacunar infarction, diarrhoea, tendon rupture, rheumatoid nodule and arthritis), 2 in cohort B (sciatica and RA) and 1 in the placebo group (asthenia). Only one of the grade 3 AEs was serious (the lacunar infarction). American College of Rheumatology 20 responses for cohorts A, B, C and placebo were 45%, 20%, 33% and 29%, respectively, at month 1, and 25%, 15%, 17% and 0%, respectively, at month 3. CONCLUSIONS: The intravenous infusion of Cx611 was in general well tolerated, without evidence of dose-related toxicity at the dose range and time period studied. In addition, a trend for clinical efficacy was observed. These data, in our opinion, justify further investigation of this innovative therapy in patients with RA. TRIAL REGISTRATION NUMBERS: EudraCT: 2010-021602-37; NCT01663116; Results. PMID- 27269295 TI - Canakinumab treatment for patients with active recurrent or chronic TNF receptor associated periodic syndrome (TRAPS): an open-label, phase II study. AB - OBJECTIVE: To evaluate the efficacy of canakinumab, a high-affinity human monoclonal anti-interleukin-1beta antibody, in inducing complete or almost complete responses in patients with active tumour necrosis factor receptor associated periodic syndrome (TRAPS). METHODS: Twenty patients (aged 7-78 years) with active recurrent or chronic TRAPS were treated with canakinumab 150 mg every 4 weeks for 4 months (2 mg/kg for those <=40 kg) in this open-label, proof-of concept, phase II study. Canakinumab was then withdrawn for up to 5 months, with reintroduction on relapse, and 4 weekly administration (subsequently increased to every 8 weeks) for 24 months. The primary efficacy variable was the proportion of patients achieving complete or almost complete response at day 15, defined as clinical remission (Physician's Global Assessment score <=1) and full or partial serological remission. RESULTS: Nineteen patients (19/20, 95%; 95% CI 75.1% to 99.9%) achieved the primary efficacy variable. Responses to canakinumab occurred rapidly; median time to clinical remission 4 days (95% CI 3 to 8 days). All patients relapsed after canakinumab was withdrawn; median time to relapse 91.5 days (95% CI 65 to 117 days). On reintroduction of canakinumab, clinical and serological responses were similar to those seen during the first phase, and were sustained throughout treatment. Canakinumab was well tolerated and clinical responses were accompanied by rapid and sustained improvement in health-related quality of life. Weight normalised pharmacokinetics of canakinumab, although limited, appeared to be consistent with historical canakinumab data. CONCLUSIONS: Canakinumab induces rapid disease control in patients with active TRAPS, and clinical benefits are sustained during long-term treatment. TRIAL REGISTRATION NUMBER: NCT01242813; Results. PMID- 27269297 TI - High soluble IL-7 receptor expression in Sjogren's syndrome identifies patients with increased immunopathology and dryness. PMID- 27269296 TI - Disease activity is associated with reduced left ventricular systolic myocardial function in patients with rheumatoid arthritis. AB - OBJECTIVES: Disease activity has emerged as a new, independent risk factor for cardiovascular disease in patients with rheumatoid arthritis (RA). We tested if disease activity in RA was associated with lower left ventricular (LV) systolic function independent of traditional cardiovascular risk factors. METHODS: Echocardiographic assessment was performed in 78 patients with RA having low, moderate or high disease activity (Simplified Disease Activity Index (SDAI) >3.3), 41 patients in remission (SDAI <=3.3) and 46 controls, all without known cardiac disease. LV systolic function was assessed by biplane Simpson ejection fraction, stress-corrected midwall shortening (scMWS) and global longitudinal strain (GLS). RESULTS: Patients with active RA had higher prevalence of hypertension and diabetes compared with patients in remission and controls (both p<0.05). LV ejection fraction (endocardial function) was normal in all three groups, while mean scMWS and GLS (myocardial function) were reduced in patients with RA with active disease compared with patients with RA in remission (95+/-18% vs 105+/-17% and -18.9+/-3.1% vs -20.6+/-3.5%, respectively, both p<0.01). Patients with RA in remission had similar scMWS and GLS as the controls. In multivariable analyses, having active RA was associated with lower GLS (beta=0.21) and scMWS (beta=-0.22, both p<0.05), both reflecting lower LV systolic myocardial function, independent of cardiovascular risk factors and LV ejection fraction. Classification of RA disease activity by other disease activity composite scores yielded similar results. CONCLUSIONS: Active RA is associated with lower LV systolic myocardial function despite normal ejection fraction and independent of traditional cardiovascular risk factors. PMID- 27269299 TI - Local collective motion analysis for multi-probe dynamic imaging and microrheology. AB - Dynamical artifacts, such as mechanical drift, advection, and hydrodynamic flow, can adversely affect multi-probe dynamic imaging and passive particle-tracking microrheology experiments. Alternatively, active driving by molecular motors can cause interesting non-Brownian motion of probes in local regions. Existing drift correction techniques, which require large ensembles of probes or fast temporal sampling, are inadequate for handling complex spatio-temporal drifts and non Brownian motion of localized domains containing relatively few probes. Here, we report an analytical method based on local collective motion (LCM) analysis of as few as two probes for detecting the presence of non-Brownian motion and for accurately eliminating it to reveal the underlying Brownian motion. By calculating an ensemble-average, time-dependent, LCM mean square displacement (MSD) of two or more localized probes and comparing this MSD to constituent single-probe MSDs, we can identify temporal regimes during which either thermal or athermal motion dominates. Single-probe motion, when referenced relative to the moving frame attached to the multi-probe LCM trajectory, provides a true Brownian MSD after scaling by an appropriate correction factor that depends on the number of probes used in LCM analysis. We show that LCM analysis can be used to correct many different dynamical artifacts, including spatially varying drifts, gradient flows, cell motion, time-dependent drift, and temporally varying oscillatory advection, thereby offering a significant improvement over existing approaches. PMID- 27269298 TI - Physical impairment and body weight history in postmenopausal women: the Women's Health Initiative. AB - OBJECTIVE: To examine whether weight history and weight transitions over adult lifespan contribute to physical impairment among postmenopausal women. DESIGN: BMI categories were calculated among postmenopausal women who reported their weight and height at age 18 years. Multiple-variable logistic regression was used to determine the association between BMI at age 18 years and BMI transitions over adulthood on severe physical impairment (SPI), defined as scoring <60 on the Physical Functioning subscale of the Rand thirty-six-item Short-Form Health Survey. SETTING: Participants were part of the Women's Health Initiative Observational Study (WHI OS), where participants' health was followed over time via questionnaires and clinical assessments. SUBJECTS: Postmenopausal women (n 76 016; mean age 63.5 (sd 7.3) years). RESULTS: Women with overweight (BMI=25.0-29.9 kg/m2) or obesity (BMI>=30.0 kg/m2) at 18 years had greater odds (OR (95 % CI)) of SPI (1.51 (1.35, 1.69) and 2.14 (1.72, 2.65), respectively) than normal-weight (BMI=18.5-24.9 kg/m2) counterparts. Transitions from normal weight to overweight/obese or to underweight (BMI<18.5 kg/m2) were associated with greater odds of SPI (1.97 (1.84, 2.11) and 1.35 (1.06, 1.71), respectively) compared with weight stability. Shifting from underweight to overweight/obese also had increased odds of SPI (1.52 (1.11, 2.09)). Overweight/obese to normal BMI transitions resulted in a reduced SPI odds (0.52 (0.39, 0.71)). CONCLUSIONS: Higher weight history and transitions into higher weight classes were associated with higher likelihood of SPI, while transitioning into lower weight classes for those with overweight/obesity was protective among postmenopausal women. PMID- 27269301 TI - Parathyroidectomy: Complex Decisions about a Complex Procedure. PMID- 27269300 TI - Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States. AB - BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism is common among patients with ESRD. Although medical therapy for secondary hyperparathyroidism has changed dramatically over the last decade, rates of parathyroidectomy for secondary hyperparathyroidism across the United States population are unknown. We examined temporal trends in rates of parathyroidectomy, in-hospital mortality, length of hospital stay, and costs of hospitalization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample, a representative national database on hospital stay regardless of age and payer in the United States, we identified parathyroidectomies for secondary hyperparathyroidism from 2002 to 2011. Data from the US Renal Data System reports were used to calculate the rate of parathyroidectomy. RESULTS: We identified 32,971 parathyroidectomies for secondary hyperparathyroidism between 2002 and 2011. The overall rate of parathyroidectomy was approximately 5.4/1000 patients (95% confidence interval [95% CI], 5.0/1000 to 6.0/1000). The rate decreased from 2003 (7.9/1000 patients; 95% CI, 6.2/1000 to 9.6/1000), reached a nadir in 2005 (3.3/1000 patients; 95% CI, 2.6/1000 to 4.0/1000), increased again through 2006 (5.4/1000 patients; 95% CI, 4.4/1000 to 6.4/1000), and remained stable since that time. Rates of in-hospital mortality decreased from 1.7% (95% CI, 0.8% to 2.6%) in 2002 to 0.8% (95% CI, 0.1% to 1.6%) in 2011 (P for trend <0.001). In-hospital mortality rates were significantly higher in patients with heart failure (odds ratio [OR], 4.23; 95% CI, 2.59 to 6.91) and peripheral vascular disease (OR, 4.59; 95% CI, 2.75 to 7.65) and lower among patients with prior kidney transplantation (OR, 0.20; 95% CI, 0.06 to 0.65). CONCLUSIONS: Despite the use of multiple medical therapies, rates of parathyroidectomy of secondary hyperparathyroidism have not declined in recent years. PMID- 27269303 TI - Damage criteria for cerebral cortex cells subjected to hyperthermia. AB - Temperatures above the normal physiological threshold may cause damage to cells and tissue. In this study, the response of a culture of dissociated cerebral cortex cells exposed to laser-induced temperature gradients was examined. The cellular response was evaluated using a fluorescent dye indicating metabolic activity. Furthermore, by using a finite element model of the heating during the pulsed laser application, threshold temperatures could be extracted for the cellular response at different laser pulse lengths. These threshold temperatures were used in an Arrhenius model to extract the kinetic parameters, i.e. the activation energy (Ea), and the frequency factor (Ac), for the system. A damage signal ratio was defined and calculated to 5% for the cells to increase their metabolism as a response to the heat. Furthermore, efficient stimulation with 20 ms long laser pulses did not evoke changes in metabolism. Thus, 20 ms could be a potential pulse length for functional stimulation of neural cells. PMID- 27269302 TI - Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences. AB - BACKGROUND AND OBJECTIVES: Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this single-center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls. RESULTS: Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3-62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0-65.8 days versus 27.5; IQR, 23.0-35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8-60.5 months versus 55.8; IQR, 40.4-71.2 months; P=0.02). Technique failure occurred in 11.5% and 10.6% of patients in the PTP and control groups, respectively. CONCLUSIONS: S. aureus is the most common causative organism of PTP. Nutritional interventions in patients who are hypoalbuminemic before catheter insertion deserve additional study. PMID- 27269304 TI - Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations. AB - We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive targeted tailored delivery system enhanced toxic responses can be attained. PMID- 27269305 TI - Fertility concerns among child and adolescent cancer survivors and their parents: A qualitative analysis. AB - Cancer diagnoses and treatment may have long-term effects on fertility. Semistructured interviews were administered to young cancer survivors (<20 years) and their parents (n = 97). Fertility related concerns were reported by 45 participants (46.4%). Themes included: distress regarding potential infertility; the effect of infertility on future relationships, self-esteem, and miscommunications/confusion about fertility status; access to fertility testing; and preservation options. Parents also reported challenges regarding how and when it was developmentally appropriate to talk to their children about fertility. The development of comprehensive consumer-driven approaches to managing the fertility concerns of young survivors and their families is essential. PMID- 27269306 TI - Inhalation of 50% Oxygen Does Not Impair Respiratory Depression During Midazolam Sedation. AB - PURPOSE: To investigate how inhalation of 50% oxygen during intravenous midazolam sedation affects respiratory variables and thus the availability of oxygen. MATERIALS AND METHODS: Study subjects were 21 healthy adult volunteers (American Society of Anesthesiologists physical status I). They were allocated to undergo midazolam sedation during high-concentration oxygen inhalation (group H) or during normal air inhalation (group N) in a single-blinded randomized crossover design, with an interval of at least 3 days between the 2 sedation sessions. In each experiment, midazolam 0.05 mg/kg was administered, after which the following variables were measured for 40 minutes: oxygen saturation by pulse oximetry (SpO2), end-tidal carbon dioxide partial pressure (ETCO2), respiration rate (RR), tidal volume (VT), and minute volume (MV). Subsequently, flumazenil 0.5 mg was administered, and the same variables were measured for 10 minutes. RESULTS: SpO2 decreased after midazolam administration in the 2 groups. SpO2 in group H was higher than that in group N at all time points. RR increased and VT decreased after midazolam administration in the 2 groups; however, in contrast to SpO2, the levels of these parameters did not meaningfully differ between groups at any time point. MV remained unchanged in the 2 groups. ETCO2 decreased similarly after midazolam administration in the 2 groups. CONCLUSION: Inhalation of 50% oxygen during midazolam sedation did not enhance respiratory depression by midazolam. This suggests that high-concentration oxygen inhalation during midazolam sedation could prevent hypoxia. PMID- 27269307 TI - Benzylic C(sp(3))-H Functionalization for C-N and C-O Bond Formation via Visible Light Photoredox Catalysis. AB - A visible light mediated highly selective benzylic C-H bond functionalization for intermolecular C-N and C-O bond formation is reported. This cross-dehydrogenative coupling reaction demonstrates a straightforward protocol for incorporating the heteroaromatics to the benzylic position. Benzylic oxidation of various alkyl aryls to corresponding carbonyl compounds has also been reported. PMID- 27269308 TI - Computational geometry assessment for morphometric analysis of the mandible. AB - This paper presents a fully automated algorithm for geometry assessment of the mandible. Anatomical landmarks could be reliably detected and distances were statistically evaluated with principal component analysis. The method allows for the first time to generate a mean mandible shape with statistically valid geometrical variations based on a large set of 497 CT-scans of human mandibles. The data may be used in bioengineering for designing novel oral implants, for planning of computer-guided surgery, and for the improvement of biomechanical models, as it is shown that commercially available mandible replicas differ significantly from the mean of the investigated population. PMID- 27269360 TI - Getting to the Heart of the Story: Using Talanoa to Explore Pacific Mental Health. AB - Talanoa is an established format for generating discussion about complex topics used throughout the Pacific. Pacific researchers use talanoa to gather data with migrant Pacific Island populations, in countries such as the United States of America, Australia, and Aotearoa/New Zealand (A/NZ). Using talanoa in this way, changes the way that the approach is used as, on the one hand it is out of its original context, and on the other hand, extends its use to gather data with Pacific Islanders. In this article, we discuss the implementation of talanoa in an explorative qualitative research project, and discuss its effectiveness and usefulness for getting to the heart of the story about Tongan interpretations of mental illness and distress. PMID- 27269361 TI - FeF3@Thin Nickel Ammine Nitrate Matrix: Smart Configurations and Applications as Superior Cathodes for Li-Ion Batteries. AB - Iron fluorides (FeFx) for Li-ion battery cathodes are still in the stage of intensive research due to their low delivery capacity and limited lifetime. One critical reason for cathode degradation is the severe aggregation of FeFx nanocrystals upon long-term cycling. To maximize the capacity and cyclability of these cathodes, we propose herein a novel and applicable method using a thin layered nickel ammine nitrate (NAN) matrix as a feasible encapsulation material to disperse the FeF3 nanoparticles. Such core-shell hybrids with smart configurations are constructed via a green, scalable, in situ encapsulation approach. The outer thin-film NAN matrix with prominent electrochemical stability can keep the FeF3 nanoactives encapsulated throughout the cyclic testing, protecting them from adverse aggregation into bulk crystals and thus leading to drastic improvements of electrode behaviors (e.g., high electrode capacity up to ~423 mA h g(-1), greatly prolonged cyclic period, and promoted rate capabilities). This present work may set up a new and general platform to develop intriguing core-shell hybrid cathodes for Li-ion batteries, not only for FeFx but also for a wide spectrum of other cathode materials. PMID- 27269362 TI - Direct Growth of Graphene Films on 3D Grating Structural Quartz Substrates for High-Performance Pressure-Sensitive Sensors. AB - Conformal graphene films have directly been synthesized on the surface of grating microstructured quartz substrates by a simple chemical vapor deposition process. The wonderful conformality and relatively high quality of the as-prepared graphene on the three-dimensional substrate have been verified by scanning electron microscopy and Raman spectra. This conformal graphene film possesses excellent electrical and optical properties with a sheet resistance of <2000 Omega.sq(-1) and a transmittance of >80% (at 550 nm), which can be attached with a flat graphene film on a poly(dimethylsiloxane) substrate, and then could work as a pressure-sensitive sensor. This device possesses a high-pressure sensitivity of -6.524 kPa(-1) in a low-pressure range of 0-200 Pa. Meanwhile, this pressure sensitive sensor exhibits super-reliability (>=5000 cycles) and an ultrafast response time (<=4 ms). Owing to these features, this pressure-sensitive sensor based on 3D conformal graphene is adequately introduced to test wind pressure, expressing higher accuracy and a lower background noise level than a market anemometer. PMID- 27269363 TI - Microscopic Mechanism and Kinetics of Ice Formation at Complex Interfaces: Zooming in on Kaolinite. AB - Most ice in nature forms because of impurities which boost the exceedingly low nucleation rate of pure supercooled water. However, the microscopic details of ice nucleation on these substances remain largely unknown. Here, we have unraveled the molecular mechanism and the kinetics of ice formation on kaolinite, a clay mineral playing a key role in climate science. We find that the formation of ice at strong supercooling in the presence of this clay is about 20 orders of magnitude faster than homogeneous freezing. The critical nucleus is substantially smaller than that found for homogeneous nucleation and, in contrast to the predictions of classical nucleation theory (CNT), it has a strong two-dimensional character. Nonetheless, we show that CNT describes correctly the formation of ice at this complex interface. Kaolinite also promotes the exclusive nucleation of hexagonal ice, as opposed to homogeneous freezing where a mixture of cubic and hexagonal polytypes is observed. PMID- 27269364 TI - Stop stalling and make PrEP for HIV available now. PMID- 27269365 TI - Birth of Four Chimeric Plastid Gene Clusters in Japanese Umbrella Pine. AB - Many genes in the plastid genomes (plastomes) of plants are organized as gene clusters, in which genes are co-transcribed, resembling bacterial operons. These plastid operons are highly conserved, even among conifers, whose plastomes are highly rearranged relative to other seed plants. We have determined the complete plastome sequence of Sciadopitys verticillata (Japanese umbrella pine), the sole member of Sciadopityaceae. The Sciadopitys plastome is characterized by extensive inversions, pseudogenization of four tRNA genes after tandem duplications, and a unique pair of 370-bp inverted repeats involved in the formation of isomeric plastomes. We showed that plastomic inversions in Sciadopitys have led to shuffling of the remote conserved operons, resulting in the birth of four chimeric gene clusters. Our data also demonstrated that the relocated genes can be co-transcribed in these chimeric gene clusters. The plastome of Sciadopitys advances our current understanding of how the conifer plastomes have evolved toward increased diversity and complexity. PMID- 27269366 TI - Short sleep duration and obesity among children: A systematic review and meta analysis of prospective studies. AB - OBJECTIVE: Previous epidemiology studies have demonstrated that short sleep duration may be associated with the development of obesity, although the effects remain controversial. This study aimed to assess epidemiologic evidence systematically on the relation between sleep duration and obesity in children. DESIGN AND METHODS: We searched the Medline, Cochrane Library, EMBASE and Science Citation Index databases and reference lists of the included articles. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using a random effects model. RESULTS: Fifty cohorts from thirteen studies were included in the pooled analysis. They included 35,540 participants from around the world. In children/adolescents the pooled OR was 1.71 (1.36-2.14; I2=91.3%), the positive association was consistent after omitting any of the studies. In subgroup analyses, the results indicated that the heterogeneity of effect may due to differences in geographical location, cut-off for short sleep duration and definition of obesity/overweight. The publication bias tests indicated a no evidence of publication bias. CONCLUSION: This meta-analysis provides evidence that short sleep duration in children is associated with a significantly increased risk of obesity. Enough sleep duration is potentially important for the prevention of obesity among children. PMID- 27269367 TI - Mediterranean diet adherence and body composition among Southern Italian adolescents. AB - INTRODUCTION: Adherence to the traditional Mediterranean diet has been associated with health benefits in young populations. The aim of this study was to evaluate the association between adherence to the Mediterranean diet and cardio-metabolic parameters in adolescents living in Sicily, Southern Italy. METHODS: A cross sectional study was conducted during two school years (2012-2013 and 2013-2014) on 1643 adolescents of 11-16 years attending 15 secondary schools. Socio demographic, dietary, lifestyle, and anthropometric data were collected. The KIDMED score was used to evaluate the adherence to the Mediterranean diet. Linear and logistic regression models were used to test the association between the variable of interest and the outcomes. RESULTS: A higher percentage of boys compared with girls was overweight (30.8% vs. 25.4%) and obese (28.7% vs. 18.5%) and only 9.1% had high adherence to the Mediterranean diet. Vegetable intake was negatively associated with being overweight/obese whereas higher intake of sweets, sugar-sweetened beverages, and fast foods was associated with overweight and obesity. A good adherence to the Mediterranean diet resulted in 30% decreased odds of being overweight or obese (odd ratio 0.70, 95% confidence interval: 0.56 0.87) in both boys and girls. An inverse correlation was found between KIDMED score and BMI, waist circumference and fat mass. No relation with blood pressure was found. CONCLUSIONS: Mediterranean dietary pattern resulted significantly associated with weight status in adolescents. These results underline the importance of providing lifestyle and dietary habits education to prevent overweight and obesity in adolescent. PMID- 27269369 TI - Surface-Charge Anisotropy of Scheelite Crystals. AB - Atomic force microscopy was employed to measure the colloidal interactions between silicon nitride cantilever tips and scheelite crystal surfaces in 1 mM KCl solutions of varying pH. By fitting the Derjguin-Landau-Verwey-Overbeek (DLVO) theoretical model to the recorded force-distance curves, the surface charge density and surface-potential values were calculated for three crystallographic surfaces including {112}, {101}, and {001}. The calculated surface-potential values were negative in both acidic and basic solutions and varied among crystallographic surfaces. The determined surface-potential values were within zeta-potential values reported in the literature for powdered scheelite minerals. The surface {101} was the most negatively charged surface, followed by {112} and {001}. The surface potential for {001} was only slightly affected by pH, whereas the surface potential for both {112} and {101} increased with increasing pH. Anisotropy in surface-charge density was analyzed in relation to the surface density of active oxygen atoms, that is, the density of oxygen atoms with one or two broken bond(s) within tungstate ions located in the topmost surface layer. On a surface with a higher surface density of active oxygen atoms, a larger number of OH(-) are expected to adsorb through hydrogen bonding, leading to a more negatively charged surface. PMID- 27269368 TI - Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans. AB - BACKGROUND: A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. METHODS: Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30mg/70kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. RESULTS: The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. CONCLUSIONS: These coordinated studies successfully established drug versus non drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID- 27269370 TI - Pharmacokinetics of 16-dehydropregnenolone hydroxypropyl-beta-cyclodextrin inclusion complex following peroral administration. AB - 16-Dehydropregnenolone (16-DHP) is an active compound with an unsatisfied in vivo behavior and poor water-solubility, which limits its clinical application. To improve its in vivo behavior and water-solubility, a Hydroxypropyl-beta Cyclodextrin (HP-beta-CD) inclusion complex of 16-DHP was prepared in this paper. Pharmacokinetic studies after oral administration of 16-DHP-HP-beta-CD at doses of 37.5, 75, 150 mg/kg were carried out to investigate its dose proportionality in rats. The relative bioavailability was researched by comparing the area under the plasma concentration-time curve of 16-DHP-HP-beta-CD and free 16-DHP after oral administration in rats at the dose of 75 mg/kg. At the same time, tissue distribution of 16-DHP-HP-beta-CD after oral administration at the dose of 240 mg/kg in mice was also investigated. Consequently, 16-DHP-HP-beta-CD appeared to be a linear pharmacokinetic character after peroral administration to the rat at the doses tested. Compared to free 16-DHP, inclusion complex could significantly improve the relative bioavailability (467%). Tissue distribution studies indicated that 16-DHP-HP-beta-CD tended to distribute into stomach, intestine, lung, brain and liver. PMID- 27269371 TI - Autologous stem cell transplantation in HIV-positive patients affected by relapsed/partially responding lymphoma: let it be. PMID- 27269373 TI - Fusion of the endoplasmic reticulum by membrane-bound GTPases. AB - The endoplasmic reticulum (ER) membrane forms an elaborate network of tubules and sheets that is continuously remodeled. This dynamic behavior requires membrane fusion that is mediated by dynamin-like GTPases: the atlastins in metazoans and Sey1p and related proteins in yeast and plants. Crystal structures of the cytosolic domains of these membrane proteins and biochemical experiments can now be integrated into a model that explains many aspects of the molecular mechanism by which these membrane-bound GTPases mediate membrane fusion. PMID- 27269372 TI - Contextual signaling in cancer. AB - The formation and maintenance of an organism are highly dependent on the orderly control of cell growth, differentiation, death, and migration. These processes are tightly regulated by signaling cascades in which a limited number of molecules dictate these cellular events. While these signaling pathways are highly conserved across species and cell types, the functional outcomes that result from their engagement are specified by the context in which they are activated. Using the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome as an illustrative platform, we discuss how NF1/RAS signaling can create functional diversity at multiple levels (molecular, cellular, tissue, and genetic/genomic). As such, the ability of related molecules (e.g., K-RAS, H-RAS) to activate distinct effectors, as well as cell type- and tissue-specific differences in molecular composition and effector engagement, generate numerous unique functional effects. These variations, coupled with a multitude of extracellular cues and genomic/genetic changes that each modify the innate signaling properties of the cell, enable precise control of cellular physiology in both health and disease. Understanding these contextual influences is important when trying to dissect the underlying pathogenic mechanisms of cancer relevant to molecularly-targeted therapeutics. PMID- 27269374 TI - Computational models of airway branching morphogenesis. AB - The bronchial network of the mammalian lung consists of millions of dichotomous branches arranged in a highly complex, space-filling tree. Recent computational models of branching morphogenesis in the lung have helped uncover the biological mechanisms that construct this ramified architecture. In this review, we focus on three different theoretical approaches - geometric modeling, reaction-diffusion modeling, and continuum mechanical modeling - and discuss how, taken together, these models have identified the geometric principles necessary to build an efficient bronchial network, as well as the patterning mechanisms that specify airway geometry in the developing embryo. We emphasize models that are integrated with biological experiments and suggest how recent progress in computational modeling has advanced our understanding of airway branching morphogenesis. PMID- 27269375 TI - Human monocytes and macrophages undergo M1-type inflammatory polarization in response to high levels of glucose. AB - Emerging data suggest that elevated glucose may promote inflammatory activation of monocytic lineage cells with the ability to injure vascular endothelial tissue of diabetic patients, however evidence in primary human monocytes and macrophages is still insufficient. We investigated the effect of high glucose concentration on the inflammatory capacity of human macrophages in vitro and examined whether similar responses were detectable in circulating monocytes from prediabetic patients. Primary monocytes were isolated from healthy blood donors and differentiated into macrophages. Differentiated macrophages were exposed to normal levels of glucose (NG), high glucose (HG) or high mannitol as osmotic pressure control (OP) for three days. Using PCR, ELISA and flow cytometry, we found that HG macrophages showed overexpression of CD11c and inducible nitric oxide synthase as well as down-regulation of arginase-1 and interleukin (IL)-10 with respect to NG and OP macrophages. Consistent with in vitro results, circulating monocytes from hyperglycemic patients exhibited higher levels of CD11c and lower expression of CD206 than monocytes from normoglycemic controls. In subjects with hyperglycemia, elevation in CD11c(+) monocytes was associated with increased obesity, insulin resistance, and triglyceridemia as well as low serum IL-10. Our data suggest that human monocytes and macrophages undergo M1 like inflammatory polarization when exposed to high levels of glucose on in vitro culture conditions and in patients with hyperglycemia. These results demonstrate that excess glucose has direct effects on macrophage activation though the molecular mechanisms mediating such a response remain to be elucidated. PMID- 27269376 TI - How dental team members describe adverse events. AB - BACKGROUND: Although some patients experience adverse events (AEs) resulting in harm caused by treatments in dentistry, few published reports have detailed how dental providers describe these events. Understanding how dental treatment professionals view AEs is essential to building a safer environment in dental practice. METHODS: The authors interviewed dental professionals and domain experts through focus groups and in-depth interviews and asked them to identify the types of AEs that may occur in dental settings. RESULTS: The initial interview and focus group findings yielded 1,514 items that included both causes and AEs. In total, 632 causes were coded into 1 of the 8 categories of the Eindhoven classification, and 882 AEs were coded into 12 categories of a newly developed dental AE classification. Interrater reliability was moderate among coders. The list was reanalyzed, and duplicate items were removed leaving a total of 747 unique AEs and 540 causes. The most frequently identified AE types were "aspiration and ingestion" at 14% (n = 142), "wrong-site, wrong-procedure, wrong patient errors" at 13%, "hard-tissue damage" at 13%, and "soft-tissue damage" at 12%. CONCLUSIONS: Dental providers identified a large and diverse list of AEs. These events ranged from "death due to cardiac arrest" to "jaw fatigue from lengthy procedures." PRACTICAL IMPLICATIONS: Identifying threats to patient safety is a key element of improving dental patient safety. An inventory of dental AEs underpins efforts to track, prevent, and mitigate these events. PMID- 27269378 TI - Why Australasian vertebrate animals are so unique - A palaeontological perspective. AB - Australasia has a unique fauna of living vertebrates, which include the oldest known species on the planet (the lungfish Neoceratodus) as well as many diverse, highly endemic families of fish, amphibians, reptiles, birds and mammals. The origin of most of the Australian vertebrate fauna has developed from two phases. Firstly, when Australia was subsumed within the greater Gondwana landmass, migration of animals from one region to another was possible by a land connection. Many of our most primitive forms of reptiles and mammals probably entered the country at this time, such as varanids, madtsooid snakes, monotremes and basal marsupials. Secondly, following the breakup of Gondwana, the isolation of Australia for its last 40 million years and subsequent changing climatic conditions drove the radiation of marsupial, reptile and amphibian families within the continent. The gradual aridification of central Australia further divided the landmass into discrete regional areas characterised by rainfall, vegetation, and climatic zones. PMID- 27269377 TI - Hop (Humulus lupulus L.) Extract and 6-Prenylnaringenin Induce P450 1A1 Catalyzed Estrogen 2-Hydroxylation. AB - Humulus lupulus L. (hops) is a popular botanical dietary supplement used by women as a sleep aid and for postmenopausal symptom relief. In addition to its efficacy for menopausal symptoms, hops can also modulate the chemical estrogen carcinogenesis pathway and potentially protect women from breast cancer. In the present study, an enriched hop extract and the key bioactive compounds [6 prenylnarigenin (6-PN), 8-prenylnarigenin (8-PN), isoxanthohumol (IX), and xanthohumol (XH)] were tested for their effects on estrogen metabolism in breast cells (MCF-10A and MCF-7). The methoxyestrones (2-/4-MeOE1) were analyzed as biomarkers for the nontoxic P450 1A1 catalyzed 2-hydroxylation and the genotoxic P450 1B1 catalyzed 4-hydroxylation pathways, respectively. The results indicated that the hop extract and 6-PN preferentially induced the 2-hydroxylation pathway in both cell lines. 8-PN only showed slight up-regulation of metabolism in MCF-7 cells, whereas IX and XH did not have significant effects in either cell line. To further explore the influence of hops and its bioactive marker compounds on P450 1A1/1B1, mRNA expression and ethoxyresorufin O-dealkylase (EROD) activity were measured. The results correlated with the metabolism data and showed that hop extract and 6-PN preferentially enhanced P450 1A1 mRNA expression and increased P450 1A1/1B1 activity. The aryl hydrocarbon receptor (AhR) activation by the isolated compounds was tested using xenobiotic response element (XRE) luciferase construct transfected cells. 6-PN was found to be an AhR agonist that significantly induced XRE activation and inhibited 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD) induced XRE activity. 6-PN mediated induction of EROD activity was also inhibited by the AhR antagonist CH223191. These data show that the hop extract and 6-PN preferentially enhance the nontoxic estrogen 2-hydroxylation pathway through AhR mediated up-regulation of P450 1A1, which further emphasizes the importance of standardization of botanical extracts to multiple chemical markers for both safety and desired bioactivity. PMID- 27269381 TI - Symbiont abundance is more important than pre-infection partner choice in a Rhizobium - legume mutualism. AB - It is known that the genetic diversity of conspecific rhizobia present in root nodules differs greatly among populations of a legume species, which has led to the suggestion that both dispersal limitation and the local environment affect rhizobial genotypic composition. However, it remains unclear whether rhizobial genotypes residing in root nodules are representative of the entire population of compatible symbiotic rhizobia. Since symbiotic preferences differ among legume populations, the genetic composition of rhizobia found within nodules may reflect the preferences of the local hosts, rather than the full diversity of potential nodulating rhizobia present in the soil. Here, we assessed whether Vicia cracca legume hosts of different provenances select different Rhizobium leguminosarum genotypes than sympatric V. cracca hosts, when presented a natural soil rhizobial population. Through combining V. cracca plants and rhizobia from adjacent and more distant populations, we found that V. cracca hosts are relatively randomly associated with rhizobial genotypes. This indicates that pre-infection partner choice is relatively weak in certain legume hosts when faced with a natural population of rhizobia. PMID- 27269382 TI - Developing an Evidence-Based Epilepsy Risk Assessment eHealth Solution: From Concept to Market. AB - INTRODUCTION: Sudden unexpected death in epilepsy (SUDEP) is possibly the most common cause of death as a result of complications from epilepsy. The need to educate and regularly review risk for all patients with epilepsy is paramount, but rarely delivered in actual clinical practice. Evidence suggests that education around SUDEP and modifiable risk variables translate into better self management of epilepsy. OBJECTIVE: We aimed to develop and implement an eHealth solution to support education and self-management of risks, in epilepsy. METHODS: We undertook an innovation pathways approach, including problem identification, feasibility assessment, design, implementation, and marketing. People with epilepsy were provided a smartphone-based app (Epilepsy Self-Monitor, EpSMon), which translates the clinical risk assessment tool into an educational and self monitoring platform, for the self-management of epilepsy. RESULTS: Results include the success of the marketing campaign, and in what areas, with an estimated reach of approximately 38 million people. EpSMon has proved a success in academic and clinical circles, attracting awards and nominations for awards. The number of users of EpSMon, after 3 months, turned out to be lower than expected (N=221). A 4-month trial of the app in use in the United Kingdom, and the success of the marketing strategy, point to necessary changes to the model of delivery and marketing, summarized in this paper. These include the marketing message, user cost model, and need for the availability of an Android version. CONCLUSIONS: EpSMon has proven a success in respect to its reception by academics, clinicians, stakeholder groups, and the patients who use it. There is work needed to promote the model and increase its acceptability/attractiveness, including broadening the marketing message, increasing its availability, and reducing its cost. Future development and promotion of the tool will hopefully inform iterative design of its core features for a receptive audience and lead to increased uptake as it is launched worldwide in 2016. PMID- 27269383 TI - Spatial distribution and pollution assessment of heavy metals in the surface sediments of the Bohai and Yellow Seas. AB - A total of 141 surface sediments were collected and analyzed for their geochemistry, total organic carbon, and grain size to assess the heavy metal pollution in the Bohai and Yellow Seas. The enrichment factor (EF) and geoaccumulation index (Igeo) of Cu, Pb, Zn, Cr, Cd, Ni, As, and Hg were calculated to assess anthropogenic contamination, and the results suggest that moderate Pb, Cd, and As contamination occurs in the study area. Sediment quality guidelines were applied to assess the adverse biological effects of these metals. The spatial distribution of the mean Effects Range-Median quotient for the vast majority of the study area is between 0.1 and 0.5, indicating low impact and potential negative biological effects. Multivariate analysis indicates that Cu, Pb, Zn, Cr, and Ni resulted primarily from lithogenic sources, whereas As, Cd, and Hg were mainly attributed to anthropogenic sources. PMID- 27269384 TI - Seasonal variation in diffusive exchange of polycyclic aromatic hydrocarbons across the air-seawater interface in coastal urban area. AB - Concentrations of 15 polycyclic aromatic hydrocarbons (PAHs) in air-seawater interface were measured over 1year in the coastal region of Incheon, South Korea. Most individual PAHs and total PAHs in air displayed statistically significant negative correlations with temperature, but not significant in seawater. Less hydrophobic compounds with three rings were at or near equilibrium in summer, while PAHs with four to six rings were in disequilibrium in all seasons, with higher fugacity gradients in colder seasons and for more hydrophobic compounds. Differently from fugacity gradients, the highest net fluxes occurred for some three- and four-ring PAHs showing the highest atmospheric concentrations. Net gaseous exchange, which was higher in winter, occurred from air to seawater with an annual cumulative flux of 2075MUg/m(2)/year (for Sigma15PAHs), indicating that atmospheric PAHs in this region, originating from coal/biomass combustion, can deteriorate the quality of seawater and sediment. PMID- 27269385 TI - Growth effects of shading and sedimentation in two tropical seagrass species: Implications for port management and impact assessment. AB - Seagrass meadows in many parts of the globe are threatened by a range of processes including port development, dredging and land clearing in coastal catchments, which can reduce water clarity and increase sedimentation pressure. As rates of seagrass loss increase, there is an urgent need to understand the potential impacts of development on these critical species. This research compares the effects of shading and burial by fine sand on two seagrass species Zostera muelleri and Halophila ovalis in Port Curtis Bay, an industrial harbour located on the continental margin adjacent to the Great Barrier Reef Heritage Area, Australia. The research finds that shading in combination with burial causes a significant decline in growth rates in both species, but that burial >=10mm reduces growth rates to a greater extent than shading. The paper concludes by discussing the implications of these findings for port management and impact assessment. PMID- 27269386 TI - Impacts of crab bioturbation and local pollution on sulfate reduction, Hg distribution and methylation in mangrove sediments, Rio de Janeiro, Brazil. AB - Mercury (Hg) and methylmercury (MeHg) are highly toxic and poorly studied in mangroves. Burrowing Uca crabs change sediment topography and biogeochemistry and thus may affect Hg distribution and MeHg formation. We studied added (203)Hg distribution, Me(203)Hg formation and sulfate reduction rates (SRR) in sediment aquariums containing Uca leptodactyla; and analyzed profiles of Me(203)Hg formation and SRR in sediment cores from two mangroves with distinct environmental impacts. MeHg formation and SRR were higher in the top (<=6cm) sediment and there was no significant difference in Hg methylation in more or less impacted mangroves. In aquariums, crab bioturbation favored Hg retention in the sediment. In the treatment without crabs, Hg volatilization and water Hg concentrations were higher. Hg methylation was higher in bioturbated aquariums but SRR were similar in both treatments. These findings suggest that bioturbating activity favors Hg retention in sediment but also promotes MeHg formation near the surface. PMID- 27269387 TI - A diffusional kurtosis imaging study of idiopathic generalized epilepsy with unilateral interictal epileptiform discharges in children. AB - BACKGROUND AND PURPOSE: To investigate brain abnormalities in children with a clinical diagnosis of idiopathic generalized epilepsy (IGE) and unilateral interictal epileptiform discharges (IED) demonstrated on electroencephalography (EEG) by diffusional kurtosis imaging (DKI). MATERIALS AND METHODS: DKI images were obtained from 18 patients (n=9 each in the left and right hemispheres). Fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) maps were estimated through voxel-based analyses, and compared with 18 normal controls matched for age and sex. RESULTS: In the left side group, the significant differences of FA were in the left fusiform gyrus and occipital lobe of the white matter (WM). The significant differences of MD were in the left pons. The significant differences of MK were in the anterior cingulate gyrus, limbic lobe, gray matter (GM) and WM of the right cerebrum. In the right side group, the significant differences of FA were in the WM of the left cerebrum. MD identified differences in the frontal, temporal, occipital, and parietal lobes of both hemispheres, especially in the limbic system, fusiform gyrus, uncus, and parahippocampal gyrus. The significant differences of MK were in the GM of the right cerebrum, particularly in the rolandic operculum and frontal lobe. CONCLUSIONS: DKI is sensitive for the detection of diffusion abnormalities in both WM and GM of IGE in children. Secondary brain abnormalities may exist in regions outside the unilateral epileptogenic zone through the limbic epileptic network, and can be detected by DKI indices FA, MD and MK. PMID- 27269389 TI - Potential drug therapies for the treatment of fibromyalgia. AB - INTRODUCTION: Fibromyalgia (FM) is a common, complex chronic widespread pain condition is characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and non pharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use. AREAS COVERED: A systemic database search has identified 26 molecular entities as potential emerging drug therapies. Advances in the understanding of the pathophysiology of FM provides clues to targets for new medications. Investigation of bioamine modulation and alpha2delta ligands and novel targets such as dopamine receptors, NMDA receptors, cannabinoid receptors, melatonin receptors and potassium channels has identified potential drug therapies. EXPERT OPINION: Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms. PMID- 27269388 TI - Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds? AB - Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success. PMID- 27269391 TI - Medicinal plants used for ophthalmological problems in Navarra (Spain). AB - ETHNOPHARMACOLOGICAL RELEVANCE: Several plants have been found to have effective against number of ophthalmological problems in Navarra. MATERIAL AND METHODS: Information was collected using semi-structured ethnobotanical interviews with 686 informants in 267 locations. In order to confirm the pharmacological application of the uses more cited by the informants, a literature review was conducted. RESULTS: A total of 57 pharmaceutical uses were reported, for 19 plants and 13 families, mainly represented by Asteraceae. The most frequently used parts were inflorescences, flowers, aerial parts, leaves and flowered aerial parts. The related affections fell into eleven categories: bloodshot eyes, watery eyes and wounds, improve vision, irrited eyelids, rheums and styes, tired eyes, conjunctivitis, eyewash, ocular problems in general. The most cited plants were: Chamaemelum nobile (L.) All., Santolina chamaecyparissus L. ssp. squarrosa (DC.) Nyman, Sambucus nigra L. ssp. nigra, Rosa agrestis Savi and Calendula officinalis L. None of them have been pharmacologically validated by Official International Organisms. From the therapeutic point of view, Allium sativum L., Foeniculum vulgare Mill., C. officinalis, and S. chamaecyparissus ssp. squarrosa deserve special attention, because ethnobotanical and pharmacological studies suggest that these medicinal plants are effective for ophthalmological problems. CONCLUSIONS: The present study constitutes a good basis for further phytochemical and pharmacological research of these four plants, which could be of interest in the design of new inexpensive, effective and safe drugs. The remaining plants are needed to be screened through standard pharmacological and clinical procedures for their activities. PMID- 27269390 TI - Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Plants from genus Lavandula have been used as anti-inflammatory drugs in Mediterranean traditional medicine. Nowadays, there is a growing interest for complementary medicine, including herbal remedies, to treat inflammatory bowel disease (IBD). AIM OF THE STUDY: To test the anti inflammatory properties of Lavandula dentata and Lavandula stoechas extracts in two inflammatory experimental models: TNBS model of rat colitis and the carrageenan-induced paw edema in mice, in order to mimic the intestinal conditions and the extra-intestinal manifestations of human IBD, respectively. MATERIAL AND METHODS: The extracts were characterized through the qualitative HPLC analysis. Then, they were assayed in vitro and in vivo. In vitro studies were performed in BMDMs and CMT-93 epithelial cells with different concentrations of the extracts (ranging from 0.1 to 100ug/ml). The extracts were tested in vivo in the TNBS model of rat colitis (10 and 25mg/kg) and in the carrageenan-induced paw edema in mice (10, 25 and 100mg/kg). RESULTS: L. dentata and L. stoechas extracts displayed immunomodulatory properties in vitro down-regulating different mediators of inflammation like cytokines and nitric oxide. They also showed anti inflammatory effects in the TNBS model of colitis as evidenced by reduced myeloperoxidase activity and increased total glutathione content, indicating a decrease of neutrophil infiltration and an improvement of the oxidative state. Besides, both extracts modulated the expression of pro-inflammatory cytokines and chemokines, and ameliorated the altered epithelial barrier function. They also displayed anti-inflammatory effects in the carrageenan-induced paw edema in mice, since a significant reduction of the paw thickness was observed. This was associated with a down-regulation of the expression of different inducible enzymes like MMP-9, iNOS and COX-2 and pro-inflammatory cytokines, all involved in the maintenance of the inflammatory condition. CONCLUSION: L. dentata and L. stoechas extracts showed intestinal anti-inflammatory effect, confirming their potential use as herbal remedies in gastrointestinal disorders. In addition, their anti-inflammatory effect was also observed in other locations, thus suggesting a possible use for the treatment of the extra-intestinal symptoms of IBD. PMID- 27269392 TI - The effect of Astragalus as an adjuvant treatment in type 2 diabetes mellitus: A (preliminary) meta-analysis. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus is a traditional Chinese medicine that is widely used for tonifying Qi (Qi mainly means life energy) to treat diabetes mellitus and its complications. AIM OF THE STUDY: We performed a meta-analysis to evaluate the effect of Astragalus in adjuvant treatment of type 2 diabetes mellitus (T2DM), and to provide novel information to improve clinical decision making. MATERIALS AND METHODS: We conducted an exhaustive database search (PubMed, EMbase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI), Wanfang data and SinoMed) of studies associated with "Astragalus" and "type 2 diabetes mellitus" until December 2015. Following quality assessment of study eligibility, the extracted data were statistically analyzed using STATA, ver. 12.0 (Stata Corp.). RESULTS: A total of 13 studies with 1054 participants were included in this meta-analysis. Two subgroups were identified, based on Astragalus dosing regimens: control group vs. Astragalus injection (AI); control group vs. Astragalus aqueous decoction (AAD). The pooled results showed that, in comparison with control group, Astragalus administration significantly reduced fasting plasma glucose (FPG) in both the AI group (WMD=-0.28, 95% CI=-0.46 to 0.10, P=0.002, I(2)=18.5%) and the AAD group (WMD=-0.83, 95% CI=-1.07 to -0.58, P=0.000, I(2)=0.0%); postprandial plasma glucose (PPG) was also significantly reduced in the AI group (WMD=-0.47, 95% CI=-0.77 to -0.17, P=0.002, I(2)=46.8%) and the AAD group (WMD=-1.19, 95% CI=-1.63 to -0.75, P=0.000, I(2)=49.3%). Fasting insulin (Fins) was significantly reduced only in the AAD treatment group (SMD=-0.33, 95% CI=-0.55 to -0.10, P=0.005, I(2)=1.0%) as was the homeostasis model assessment insulin resistance index (HOMA-IRI) levels (SMD=-1.66, 95% CI= 3.24 to -0.09, P=0.038, I(2)=94.0%). Although AAD treatment significantly reduced levels of glycated hemoglobin A1c (HbA1c) (WMD=-1.77, 95% CI=-3.06 to -0.47, P=0.007, I(2)=90.8%), AI treatment failed to show significant efficacy (WMD= 0.28, 95% CI=-0.63 to 0.06, P=0.102, I(2)=83.8%). Sensitivity analysis failed to detect outliers in all studies while Egger's linear regression test revealed a lack of publication bias in this meta-analysis (P=0.771, 95%CI =-3.51 to 4.56). CONCLUSIONS: Astragalus may be beneficial as an adjuvant therapy in the treatment of type 2 diabetes. However, due to the limited quality of existing studies, further high-quality studies are warranted before definitive conclusions may be reached. PMID- 27269393 TI - Estimating the most efficient allocation of interventions to achieve reductions in Plasmodium falciparum malaria burden and transmission in Africa: a modelling study. AB - BACKGROUND: Reducing the burden of malaria is a global priority, but financial constraints mean that available resources must be allocated rationally to maximise their effect. We aimed to develop a model to estimate the most efficient (ie, minimum cost) ordering of interventions to reduce malaria burden and transmission. We also aimed to estimate the efficiency of different spatial scales of implementation. METHODS: We combined a dynamic model capturing heterogeneity in malaria transmission across Africa with financial unit cost data for key malaria interventions. We combined estimates of patterns of malaria endemicity, seasonality in rainfall, and mosquito composition to map optimum packages of these interventions across Africa. Using non-linear optimisation methods, we examined how these optimum packages vary when control measures are deployed and assessed at national, subnational first administrative (provincial), or fine-scale (5 km(2) pixel) spatial scales. FINDINGS: The most efficient package in a given setting varies depending on whether disease reduction or elimination is the target. Long-lasting insecticide-treated nets are generally the most cost-effective first intervention to achieve either goal, with seasonal malaria chemoprevention or indoor residual spraying added second depending on seasonality and vector species. These interventions are estimated to reduce malaria transmission to less than one case per 1000 people per year in 43.4% (95% CI 40.0-49.0) of the population at risk in Africa. Adding three rounds of mass drug administration per year is estimated to increase this proportion to 90.9% (95% CI 86.9-94.6). Further optimisation can be achieved by targeting policies at the provincial level, achieving an estimated 32.1% (95% CI 29.6-34.5) cost saving relative to adopting country-wide policies. Nevertheless, we predict that only 26 (95% CI 22-29) of 41 countries could reduce transmission to these levels with these approaches. INTERPRETATION: These results highlight the cost-benefits of carefully tailoring malaria interventions to the ecological landscape of different areas. However, novel interventions are necessary if malaria eradication is to be achieved. FUNDING: Bill & Melinda Gates Foundation, UK Medical Research Council. PMID- 27269410 TI - Comparison of intravenous ferrous sucrose and oral ferrous sulphate in treatment of postpartum iron deficiency anemia. AB - OBJECTIVE: The objective of the study was to evaluate the efficacy, safety and tolerability of intravenous ferrous sucrose, compared to oral ferrous sulphate in women with postpartum iron deficiency anemia (IDA). METHODS: In a single center, randomized, controlled study, 352 patients with hemoglobin 9 gm/dl or less and serum ferritin of <15 MUg/l two days after delivery were equally randomized to receive intravenous ferrous sucrose (up to three calculated replacement doses) or oral ferrous sulphate (150 mg twice daily for six weeks). Primary measures were to assess the rise in hemoglobin (Hb) and serum ferritin. RESULTS: By day 5, the Hb level in women treated with intravenous ferrous sucrose had rised from 8.48 +/ 0.47 to 9.4 +/- 0.56 gm/dl. Women treated with intravenous ferrous sucrose had significantly higher Hb levels on day 5, day 14 and day 40 (p < 0.01) than those treated with oral ferrous sulphate. Throughout the study, ferritin level rose rapidly in those treated with intravenous iron and remained significantly higher than in those treated with oral iron (p < 0.001). CONCLUSION: Intravenous ferrous sucrose increases Hb level more rapidly than ferrous sulphate in women with postpartum IDA. It also replenishes iron stores more rapidly with better tolerability. PMID- 27269411 TI - Self-Driven Desalination and Advanced Treatment of Wastewater in a Modularized Filtration Air Cathode Microbial Desalination Cell. AB - Microbial desalination cells (MDCs) extract organic energy from wastewater for in situ desalination of saline water. However, to desalinate salt water, traditional MDCs often require an anolyte (wastewater) and a catholyte (other synthetic water) to produce electricity. Correspondingly, the traditional MDCs also produced anode effluent and cathode effluent, and may produce a concentrate solution, resulting in a low production of diluate. In this study, nitrogen-doped carbon nanotube membranes and Pt carbon cloths were utilized as filtration material and cathode to fabricate a modularized filtration air cathode MDC (F MDC). With real wastewater flowing from anode to cathode, and finally to the middle membrane stack, the diluate volume production reached 82.4%, with the removal efficiency of salinity and chemical oxygen demand (COD) reached 93.6% and 97.3% respectively. The final diluate conductivity was 68 +/- 12 MUS/cm, and the turbidity was 0.41 NTU, which were sufficient for boiler supplementary or industrial cooling. The concentrate production was only 17.6%, and almost all the phosphorus and salt, and most of the nitrogen were recovered, potentially allowing the recovery of nutrients and other chemicals. These results show the potential utility of the modularized F-MDC in the application of municipal wastewater advanced treatment and self-driven desalination. PMID- 27269412 TI - Surgical treatment of class II dento-facial deformity during adolescence: Long term follow-up. AB - PURPOSE: The purpose of this study is to evaluate the long-term stability of patients operated during adolescence on the base of clinical measurements and cephalometric analysis. Although, the potential benefits of early orthognathic surgery are known to be a reduction in treatment times and a greater healing potential leading to a better adaptation and stability of the occlusion, muscles, bones and joints, no consensus can be found in literature on the minimum age for surgical correction. MATERIALS AND METHODS: In this study, thirty patients (age <= 15) with a class II dento-skeletal malocclusion were selected, of which 11 having a hyperdivergent (II,1) and 19 a hypodivergent (II,2) growth pattern, representing 2 distinct groups with a different treatment plan and long-term behavior. RESULTS AND CONCLUSION: Observing the performance of all parameters over-time, it is seen that subjects belonging to division II,2 have a modification of the growth vectors maintaining the harmonious development between the jaws and the facial aesthetics. Less predictable is the trend in hyperdivergent patients, which are more prone to relapse in the long-term. Early surgery in these patients should be considered in the light of the degree of deformity and its influence felt by the patient on his development of self-image and interpersonal relationship. PMID- 27269413 TI - Incidence and predictors of bleeding complications after percutaneous coronary intervention. AB - BACKGROUND: Bleeding complications remain one of the most important challenges in percutaneous coronary intervention (PCI), particularly in Asians who are known to be vulnerable to the use of antiplatelets or anticoagulants. However, the incidence and predictors of bleeding complications after PCI have not been thoroughly investigated in Japan. METHODS: We studied 13,075 consecutive patients in a Japanese multicenter PCI registry (Japan Cardiovascular Database - Keio interhospital Cardiovascular Study: JCD-KiCS) from September 2008 to March 2014. Multivariate logistic regression analysis was performed to investigate independent predictors of bleeding complications, and to create three risk prediction models for bleeding events. Model 1 included patients' characteristics alone. In model 2, we added patients' clinical presentation. Model 3 included covariates in model 2 along with angiographic and technical factors. Model discrimination was assessed using the area under the receiver operating curve (AUC). RESULTS: Overall, bleeding complications, according to the pre-specified US National Cardiovascular Data Registry criteria, were observed in 402 patients (3.1%). Independent predictors of bleeding complications included age, female gender, previous PCI, previous heart failure, hemodialysis (variables included in model 1), ST-elevation and non-ST-elevation myocardial infarction, cardiogenic shock (added in model 2), transradial intervention, use of intra-aortic balloon pumping or a rotablator, and PCI for chronic total occlusion (added in model 3). Above all, previous PCI and transradial intervention were inverse predictors of bleeding. The predictability of the risk models improved as the number of variables increased, with AUC of 0.667, 0.747, and 0.791 for models 1, 2, and 3, respectively. CONCLUSIONS: The incidence of bleeding complications among Japanese PCI patients was approximately 3% in standard nomenclature, which is equivalent to that of other international registries. Patients' characteristics, clinical presentation, and angiographic and technical factors all independently contributed to its prediction. PMID- 27269415 TI - Gene- and Stem Cell-Based Approaches to Regulate Hypertrophic Differentiation in Articular Cartilage Disorders. AB - Hypertrophy is a key component of endochondral ossification, the process controlling skeletal (cartilage, bone) development by differentiation of mesenchymal stem cells. Hypertrophic events also occur on cartilage injury such as during osteoarthritis (OA) and to a certain extent in focal lesions that may lead to OA if let untreated. Strategies based on the delivery on therapeutic genes and progenitor cells (the cells mostly recruited in spontaneous and guided repair) offer potential tools to delay or even prevent such undesirable events in sites of cartilage damage. The goal of this review is to revisit the mechanisms of hypertrophy during skeletal development and diseases and to provide an overview of the most recent advances in gene and stem cell therapy in the field of cartilage repair. PMID- 27269414 TI - Use of Hes1-GFP reporter mice to assess activity of the Hes1 promoter in bone cells under chronic inflammation. AB - Notch signaling plays a critical role in maintaining bone homeostasis partially by controlling the formation of osteoblasts from mesenchymal stem cells (MSCs). We reported that TNF activates Notch signaling in MSCs which inhibits osteoblast differentiation in TNF transgenic (TNF-Tg) mice, a mouse model of chronic inflammatory arthritis. In the current study, we used Hes1-GFP and Hes1-GFP/TNF Tg mice to study the distribution and dynamic change of Notch active cells in normal and inflammatory bone loss and mechanisms mediating their enhanced proliferation. We found that Hes1-GFP+ cells are composed of cells expressing mesenchymal, hematopoietic and endothelial surface markers. CD45-/Hes1-GFP+ cells express high levels of mesenchymal markers and form CFU-F and CFU-ALP colonies. Expansion of CFU-F colonies is associated with a rapid increase in Hes1-GFP+ cell numbers and their GFP intensity. The GFP signal is lost when a CFU-F colony differentiates into an ALP+ osteoblast colony. TNF increases the numbers of CD45 /Hes1-GFP+ cells, which are stained negatively for osteoblast marker osteocalcin and localized adjacent to endosteal and trabecular bone surfaces. CD45-/Hes1-GFP+ cells in Hes1-GFP/TNF-Tg mice have increased BrdU incorporation and PDGFRbeta levels. TNF increases the number of proliferating Hes1-GFP+ cells, which is prevented by a specific PDGFRbeta inhibitor. Notch inhibition blocks TNF-mediated PDGFRbeta expression and cell proliferation. Thus, TNF-induced MSC proliferation is mediated by PDGFRbeta signal, which works at downstream of Notch. Hes1-GFP mice can be used to assess the activation status of Notch in bone cells. PMID- 27269416 TI - Randomized, controlled trial of povidone-iodine to reduce simple traumatic wound infections in the emergency department. AB - INTRODUCTION: Povidone Iodine (PVI) has been used to prevent wound infection for a long time, yet the merits and effectiveness of this agent in reducing the rates of infection in simple traumatic wounds have been debated. The aim of this study is determine the effect of PVI as skin disinfectant in preventing simple traumatic wound infection after repair in emergency departments. METHODS: This study is a single-blind, randomized, controlled trial, conducted at the emergency departments of two university hospitals. In this trial, those collecting and analyzing data were unaware of the assigned treatment. Participants included ED patients with simple traumatic wounds, randomly assigned to either experiment or control groups. Wounds were similarly irrigated with normal saline in both groups. But the skin around the wounds of patients in the experiment group was cleansed by PVI solution. The patients were followed till their next ED visit for stitch removal. The presence or absence of wound infection was considered as the primary outcome and assessed by an ED physician. RESULTS: In total, 444 patients were screened and included in the study. The patients were statistically similar according to their baseline characteristics. Men constituted 85% of the study participants. The highest numbers of reported wound sites belonged to head (30%), lower limbs (24%) and upper limbs (19%) accordingly. The rates of infections in the experiment and control groups were similar (p=0.231) but a significant association was observed between the rate of infections and wound location. Lower limbs (OR=9.23, p<0.0001) and upper limbs (OR=5.47, p=0.011) indicated the highest risks of wound infections among other locations. CONCLUSION: Our study showed that using PVI in the management of traumatic wounds did not reduced rate of infections. PMID- 27269417 TI - Analysis of relevant proteins from bone graft harvested using the reamer irrigator and aspirator system (RIA) versus iliac crest (IC) bone graft and RIA waste water. AB - PURPOSE: Femoral reaming using a Reamer Irrigator Aspirator (RIA) can produce greater than three liters of waste water per procedure, which contains cells and proteins that could promote bone healing. This purpose of this study was to determine the protein profile of RIA waste water and compare protein synthesis by cells harvested via RIA versus iliac crest (IC) bone graft. METHOD: Bone graft was collected from 30 patients-15 using RIA from the femur and 15 harvested from the iliac crest. Waste water collected during the RIA procedure was analyzed in 12 patients. Cells from each graft were cultured in monolayer using growth media for 14days and inductive media for the next 14days. Media samples were collected on days 14, 21, and 28. Proteins for analysis were chosen based on their potential in bone healing, pro-inflammatory, and anti-inflammatory processes. RESULTS: Proteins present in RIA waste water indicate the potential for clinical use of this filtrate as an adjunct for enhancing bone production, healing, and remodeling. Similarly, cells cultured from RIA bone graft harvests compared favorably to those from iliac crest bone grafts with respect to their potential to aid in bone healing. CONCLUSION: RIA waste water has potential to serve as an autogenic and allogenic enhancer for bone healing. Continued development of processing protocols for viable commercial use of the waste water and pre clinical studies designed to evaluate RIA waste water products for bone healing are ongoing. PMID- 27269418 TI - Fixation of displaced femoral neck fractures in young adults: Fixed-angle devices or Pauwel screws? AB - BACKGROUND: We sought to compare the incidence of complications after fixation of displaced femoral neck fractures in young adults treated with fixed-angle devices versus multiple cancellous screws and a trochanteric lag screw (Pauwel screw). METHODS: We conducted a retrospective cohort study at a level I trauma centre. Sixty-two skeletally mature patients (age range, 16-60 years) with displaced femoral neck fractures were included in the study. Forty-seven were treated with a fixed-angle device (sliding hip plate with screw or helical blade) and 15 with multiple cancellous screws placed in a Pauwel configuration. The main outcome measure was postoperative complication of osteonecrosis or nonunion treated with a surgical procedure. RESULTS: Significantly fewer failures occurred in the fixed angle group (21%) than in the screws group (60%) (p=0.008). Osteonecrosis was rare in the fixed-angle group, occurring in 2% of cases versus 33% of cases in the screws group (p=0.002). Consistent with previous studies, good to excellent reductions were associated with a failure rate of 25% and fair to poor reductions were associated with a failure rate of 55% (p=0.07). The best-case scenario of a good to excellent reduction stabilised with a fixed-angle device yielded a success rate of 85%. CONCLUSION: In young patients with displaced high-energy femoral neck fractures, fixed-angle devices resulted in fewer treatment failures than did Pauwel screws. PMID- 27269419 TI - Pharmacogenomics of multifactorial diseases: a focus on psoriatic arthritis. AB - This review will outline the current pharmacogenomics knowledge about psoriatic arthritis with a special attention to the perspectives and the challenges for its implementation in the clinical practice. To date, different drugs have been developed to contrast the symptoms and the progression of psoriatic arthritis. However, patients have shown high variability of drug response in relation to their genetic makeup. In this context, the advances made in the knowledge and the potentialities of genome-drugs associations paved the path for the development of a precision medicine. In fact, these associations may be successfully combined with the environment information to provide new strategies able to prevent and improve the disease management as well as to enhance the patients quality of life. PMID- 27269420 TI - Expanding the bounds of military psychiatry: three clinical encounters. AB - This paper deals with clinical situations frequently encountered in military psychiatry. Using three narratives of soldiers assessed at the Israeli Defence Forces (IDF) during a period of marked conflict between Israel and the Palestinian Authority, the author portrays ethical dilemmas generated during assessments for fitness to go to combat. When the focus of the assessment is the soldier's refusal to serve in the army, particularly during periods of increased conflict, the psychiatrist faces a dilemma because of double loyalties, to the army of which he is a part, and to the soldier and his right to live. Based on previous literature and experience, some cases of refusal to serve may be understood going beyond the boundaries imposed by the medical model. The author discusses these issues in the context of Israeli society. In Israel, conscription is universal, and the army is not professional. However, given the lack of social legitimacy in Israel for refusal to serve in the IDF due to conscientious objection, soldiers who are otherwise aware of the ethical dilemmas imposed upon them by the harsh Israeli reality are left with no option other than to get exempted from military duties on psychiatric grounds. The author discusses how social and historical factors contribute to the construction of psychiatric and psychological symptoms. PMID- 27269421 TI - Meaning of 9/11 for two Pakistani communities: from external intruders to the internalisation of a negative self-image. AB - Since September 11, the increase in international tensions and the subsequent wars in Afghanistan and Iraq have created turmoil and fears in immigrant communities, fanned by the media in the context of the war against terrorism. This paper aims to compare the meaning systems evoked around 9/11 within two Pakistani groups-an immigrant community in Montreal and a group in Karachi. It also intends to examine the representation of themselves and of the 'Other' within these two groups. Results suggest that both Karachi and Montreal Pakistani respondents favour a conspiracy scenario which protects the Muslim community from the responsibility of 9/11 events. They refer to an argumentation process based on 'proofs', thus mirroring the political rhetoric used by the US government and its allies to justify the military intervention in Iraq. In the Montreal group, the pervasive feeling of fear and the bleak image that the community has of itself support the hypothesis of an immigrant internalisation of the negative representations of Muslim and South Asian identities in the North American context. The negative self-image observed in these minority groups indicates that more effort than ever should be dedicated to understanding the impact of the present international context on minority-majority relations in multi-ethnic societies. It is as if America is sitting right here in the living room with us ... We have to ask them permission to breathe. (Parveen, Karachi). PMID- 27269422 TI - The paediatric clinic as negotiated social space. AB - Contemporary urban diversity combined with increasing specialisation in tertiary care, technological innovations, and complexity of pathologies, render patient physician relations challenging for both patients and practitioners. Based on ongoing research in a university paediatric hospital in Montreal, this paper examines how patient-physician relations are played out in the space of the clinic in which a set of social, cultural, structural and asymmetrical relations intertwine. Through an ethnographic approach, which includes the observation of multi-disciplinary clinical settings as well as interviews with clinicians and families (migrants and non-migrants), the paper examines how the 'images' of both the patient (his family) and the physician play an active role in the clinical encounter. Interpretations of parental attitudes by practitioners are linked to their perceived background within the local and institutional configuration of norms and values, including the notion of a 'good parent'. This research problematises the concept of culture as it is engaged by clinicians (by excluding their own) and promotes reflection on an anthropologically informed clinical practice. PMID- 27269423 TI - Trichinellosis: a possible link between human infection and the traditional earth oven or 'mumu' method of cooking in Morehead District, Western Province, Papua New Guinea. AB - OBJECTIVE: To investigate if the traditional method of cooking pig meat in an earth-oven or mumu, as practiced by people in Morehead District, Western Province, Papua New Guinea (PNG), could be a source of infection with Trichinella papuae and of the disease trichinellosis. PROCEDURE: As the locality lacks suitable river stones normally used in a mumu in PNG, people use various substitute materials, such as pieces of termite mounds, balls of dried clay and small rough stones. Samples of these were tested and compared with conventional mumu stones in their capacity to retain heat. RESULTS: None of the substitute materials tested was as efficient in retaining heat as the conventional mumu stones. CONCLUSIONS: Cooking pig meat in a mumu in Morehead District has the potential to be a source of infection with T. papuae. Loss of heat in a Morehead mumu is accelerated probably as the mumu is prepared on the surface of the ground and not in a shallow pit or depression as is the custom elsewhere in the country. PMID- 27269424 TI - Perspectives on access to personal health information in New Zealand/Aotearoa. AB - This study used group interviews to explore Maori and European New Zealander (Pakeha) perspectives on access to personal health information. Two predominant themes emerged: the tension between the individual and society, and differences inherent in the use of formal and informal moral codes. Maori and Pakeha differed in their concept of autonomy and relied on distinct moral codes when considering questions of access; Western values and moral codes were notably less relevant to Maori who described distinct, collectivist means of ensuring social care of the sick and dying. Pakeha but not Maori participants often used hypothetical situations to reach an abstract determination of 'who should know'; the latter instead used personal experience to decide case-by-case. Generational differences were also evident, particularly in the Maori groups. In conclusion, culture should be considered in access to personal health information in New Zealand. Similar cultural variation is likely to be found in other countries; recognition of such differences will help ensure that access to sensitive information is appropriate, inclusive, and ethical. PMID- 27269425 TI - 'A routine thing': clinician strategies for implementing HIV testing for at-risk patients in a busy healthcare organisation (and implications for implementation of other new practice recommendations). AB - Increasing HIV testing is a necessary step toward control of the disease. Many experts suggest routinely offering HIV testing to specific population segments. We explore provider discourse regarding an HIV test implementation project with the aim of illuminating a structurally emergent clinician strategy for promoting testing and the socio-cultural factors underlying it. Twenty US Veterans Affairs Healthcare System clinical care providers were interviewed. Using standard anthropological text analysis techniques, themes, their relationships, and the significance of these for increasing appropriately targeted HIV test offers were established. Presenting the HIV test offer to their patients as if routine ('routinisation') supported providers' desire to do no harm by lessening the test's potential stigma. Offering the test helped providers maintain professional integrity: it empowered veterans to realise access to care and fit with providers' sense of honour and duty. Routinising HIV testing also helped providers to manage scarce time effectively. Findings can be leveraged to support routine screening's successful roll-out. The carefully managed introduction of routine HIV test offering policies will formalise and legitimise productive strategies of destigmatisation already being enacted by some front-line providers. The fact that routinisation strategies are in use although HIV testing is not actually routine attests to the potential power routinisation has to reduce HIV's stigma, increase HIV test uptake, and thereby improve access to care. What I've learned about tough questions is: The more routine you make them, the easier it is to get the questions answered, the less destructive it is to the relationship and that's the sort of paradigm I've come to believe in and will use now into the future. (Marvin K, MD). PMID- 27269426 TI - Metaphors to cure by: Tojolab'al Maya midwifery and cognition. AB - The southern Mexican state of Chiapas has the highest concentration of indigenous peoples in Mexico and ranks first among all states for the percentage of births attended by nurses or midwives. Efforts to improve maternal and child health in this region, therefore, must engage indigenous midwives and healers in a meaningful way, which presupposes an understanding and respect for the area's rich ethnomedical traditions. To this end, the present paper synthesises findings of in-depth ethnographic fieldwork by the author among Tojolab'al Mayan midwives. Several cultural themes underlying cognitive models of reproductive health are presented. Results indicate that several prominent metaphors relating to natural cycles of agricultural growth, death and regeneration form a bridge that links human fertility and illness to a living, dynamic cosmology. As suggested by quantitative analyses presented here, these 'metaphors to cure by' provide clues that are likely to prove central to the translation of public health programmes and clinician-patient communication in this population. PMID- 27269427 TI - Tairyoku as a belief system of health and illness: a study of cancer patients in Japan. AB - The aim of this paper is to investigate the concept of tairyoku (body power) within the context of palliative care in contemporary Japan, and to explore its use by cancer patients at palliative care units (PCUs). Tairyoku is thought to be vital energy, analogous to qi in Chinese Medicine. In this paper it is shown that tairyoku is used to monitor bodily condition by patients and that it plays an important role in treatment decision-making for them. Medical professionals also use the word tairyoku; however, they do not agree with the patients' idea of increasing tairyoku in order to cure cancer. This situation causes disagreement about treatment between patients and medical staff at PCUs; however, this paper will show that tairyoku is the important concept to help patients manage their illness and sustain their autonomy, and finally accept imminent death. PMID- 27269428 TI - Stress as an idiom for resilience: health and migration among sub-Saharan Africans in Switzerland. AB - Most research on migrants examines what makes them ill. Inspired by Antonovsky's salutogenic approach, this study shifts the perspective and asks why migrants stay healthy. At the centre of interest are sub-Saharan Africans living in Switzerland who consider themselves and/or are considered by others as mastering problems affecting their health. The mixed Swiss-African research team explored meanings of health and resilience in 20 case studies in Zurich and Basel and five group discussions in Bern, Biel and Geneva. The data show that migrants with resilient trajectories have a dynamic and multi-dimensional understanding of health. Moreover, they have learnt to interpret difficulties as 'stress': a popular illness concept in Switzerland and Europe but less known in their home countries. The paper argues that resilience is closely related with the appropriation of 'stress' as an illness concept: it not only gives meaning and helps to explain diffuse symptoms of ill-health, it also offers an agenda for action and contributes to their feeling of social belonging in the host country. These findings have important implications for policy and practice in the rapidly changing field of migration and health. PMID- 27269429 TI - Keeping the feet of the gods and the saints warm: mundane pragmatics in times of suffering and uncertainty. AB - In this article the author writes about mundane pragmatics, or everyday deeds, in times of suffering and uncertainty. Such pragmatics differ from cultural practices such as biomedical therapies or individual health-seeking behaviour patterns. Medical anthropologists and others working in the field of health and illness often overlook such pragmatics. However, these actions are of great social value and express the connectedness and bonds between people. They also express our deep beliefs, hopes, powerlessness and vulnerability. PMID- 27269432 TI - Breastfeeding Associated with Reduced Mortality in Women with Breast Cancer. AB - OBJECTIVE: To study whether breastfeeding affects survival from breast cancer. BACKGROUND: There are few studies on the relationship between breastfeeding, reproductive health, and breast cancer survival. This study is a follow-up of an earlier study showing no convincing associations between breastfeeding and breast cancer prognostic parameters. METHODS: From a cohort of 629 women with primary breast cancer having undergone surgery between 1988 and 1992, 341 were traced and consequently studied 20 years later regarding breastfeeding and reproductive variables, as well as for prognostic parameters such as the Nottingham histological grade, tumor size, lymph node status, and vascular invasion (VI). Multivariate Cox regression analyses were used. RESULTS: Increased breast cancer mortality was associated with the Nottingham prognostic index (hazard rate ratio (HR) 4.47; 95% confidence interval (CI) 2.04-9.79), VI (HR 3.44; CI 2.03-5.82), fewer pregnancies (three categories; >2, 1-2, 0) (HR per category 2.04; CI 1.34 3.11), and breastfeeding <=6 months (HR 2.74; CI 1.41-5.35). The HRs for overall mortality were, as expected, lower for the Nottingham prognostic index (HR 1.28; CI 0.89-1.85) and VI (HR 2.09; CI 1.38-3.17), and they were slightly lower for the number of pregnancies (HR 1.61; CI 1.48-4.59), but notably similar for breastfeeding (HR 3.01;CI 1.92-4.73). CONCLUSION: A total breastfeeding history >6 months and pregnancy are associated with both greater overall and breast cancer-specific survival for women diagnosed with breast cancer, having lived long enough for other causes of death to contribute substantially to mortality. PMID- 27269431 TI - Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus. AB - To determine if a hypersensitive-type lung pathology might occur when mice were given an inactivated MERS-CoV vaccine and challenged with infectious virus as was seen with SARS-CoV vaccines, we prepared and vaccinated mice with an inactivated MERS-CoV vaccine. Neutralizing antibody was induced by vaccine with and without adjuvant and lung virus was reduced in vaccinated mice after challenge. Lung mononuclear infiltrates occurred in all groups after virus challenge but with increased infiltrates that contained eosinophils and increases in the eosinophil promoting IL-5 and IL-13 cytokines only in the vaccine groups. Inactivated MERS CoV vaccine appears to carry a hypersensitive-type lung pathology risk from MERS CoV infection that is similar to that found with inactivated SARS-CoV vaccines from SARS-CoV infection. PMID- 27269433 TI - Appendiceal mucocoele with midgut malrotation. AB - Introduction Malrotation of the midgut and appendiceal mucocoele are both extremely rare pathological conditions in adults. To our knowledge, there are only two reported cases in the English literature with a combination of both conditions. Case History A 65-year-old man presented with a 10-day history of upper abdominal pain associated with abdominal bloating and weight loss. He was otherwise fit and healthy with no significant past medical history. On examination, his abdomen was soft with tenderness and palpable fullness over the left upper quadrant. The initial blood test, chest x-ray and abdominal x-ray demonstrated no significant abnormality. Computed tomography showed a 17cm x 8cm x 6cm elongated cystic mass with possible malrotation of the intestines. Histopathology showed a low grade mucinous tumour of the appendix. At 12 months following surgery, there was no evidence of recurrence or postoperative complications and the patient was discharged from the care of the colorectal team. Conclusions We report a patient with a combination of two rare conditions. This case illustrates how a combination of pathologies can present a challenge to the unwary general surgeon. PMID- 27269434 TI - Schwannoma of the biliary tract resembling cholangiocarcinoma: A case report and review. AB - Schwannomas are benign tumours derived from Schwann cells and are extremely rare in the biliary tract. We present the case of a 62-year-old patient with a common bile duct schwannoma that resembled a cholangiocarcinoma. We also review all 17 previously published cases of schwannoma of the biliary tract and discuss the challenges of preoperative diagnosis. PMID- 27269435 TI - Right iliac fossa pain from a grossly enlarged and torted appendix in a patient with known colitis. AB - A 27-year-old man with a background of well controlled colitis presented with a 12-hour history of central abdominal pain, nausea, vomiting and fever. A diagnostic laparoscopy revealed an extremely large, gangrenous appendix, which had descended into the pelvis posterior to adhesions in the right iliac fossa and was torted 720 degrees . The decision was taken to convert to a lower midline laparotomy and as the base appeared healthy, a standard appendicectomy was performed. The patient recovered well and was discharged after two days. The appendix measured 104mm x 53mm x 51mm. Histology revealed acute haemorrhagic and necrotising appendicitis with foci of impending perforation. There was no malignancy or mucocoele. Acute torsion (or volvulus) of the appendix is an unusual cause of this common general surgical emergency. PMID- 27269436 TI - Towards an evidence-based management of right iliac fossa pain in the over 50 year-old patient. AB - Introduction Right iliac fossa pain is a common presenting complaint to general surgery. The differential diagnosis is wide, particularly in the elderly. Computed tomography (CT) is often used in the 'older' population, as they have a higher prevalence of acute colonic diverticulitis and colonic neoplasia, both of which should be identified prior to surgery. There is, however, no published evidence to support this practice. Methods We retrospectively reviewed the records of all patients aged over 50 years who presented with right iliac fossa (RIF) pain to a district general hospital. We determined whether tenderness was predominantly right- or left-sided and whether systemic inflammatory response syndrome (SIRS) was present on admission. The use of imaging modalities, their results and, if performed, operative findings were recorded. Results Of 3160 patients identified, 89 met the inclusion criteria. Diagnoses included appendicitis (27%), neoplasia (15%), non-specific abdominal pain (15%) and acute colonic diverticulitis (10%). CT was performed in 82% of patients, with a sensitivity of 97% based on operative findings. Six patients underwent surgery without a scan, two of whom required a change in the planned procedure due to unexpected findings. Conclusions Unless contraindicated, CT scanning should be mandatory in patients aged over 50 years presenting with signs of peritonism in the RIF or lower abdomen. PMID- 27269437 TI - Type 4 appendiceal diverticulum within a de Garengeot hernia. AB - A de Garengeot hernia is defined as an incarcerated femoral hernia containing the vermiform appendix. We describe the case of a patient with a type 4 appendiceal diverticulum within a de Garengeot hernia and delineate valuable learning points. A 76-year-old woman presented with a 2-week history of a non-reducible painless femoral mass. Outpatient ultrasonography demonstrated a 36mm * 20mm smooth walled, multiloculated, partially cystic lesion anterior to the right inguinal ligament in keeping with an incarcerated femoral hernia. Intraoperatively, the appendix was found to be incarcerated in the sac of the femoral hernia and appendicectomy was performed. Histopathology demonstrated no evidence of inflammation in the appendix. However, an incidental appendiceal diverticulum was identified. It is widely recognised that a de Garengeot hernia may present with concomitant appendicitis, secondary to raised intraluminal pressure in the incarcerated appendix. Appendiceal diverticulosis is also believed to develop in response to raised pressure in the appendix and may therefore develop secondary to incarceration in a de Garengeot hernia. To our knowledge, only one such case has been described in the literature. A de Garengeot hernia is a rare entity, which poses significant diagnostic challenges. A high index of clinical suspicion is necessary as these hernias are at particularly high risk of perforation and so prompt surgical management is paramount. PMID- 27269438 TI - Portobiliary fistula following laparoscopic cholecystectomy. AB - The laparoscopic approach has replaced open surgery as the gold standard for cholecystectomy. This technique is, however, associated with a greater incidence of bile duct injuries (BDIs). We report a case of portobiliary fistula (PBF), a rare complication of BDI, occurring post laparoscopic cholecystectomy (LC). PBF has been reported after procedures such as endoscopic retrograde cholangiopancreatography and pathologies such as liver abscesses, but only once previously in the setting of LC. We discuss the management of this patient with apparent dual pathology, and summarise other aetiologies that may give rise to this condition. PMID- 27269439 TI - Prophylactic mesh use during primary stoma formation to prevent parastomal hernia. AB - Introduction Parastomal hernia (PSH) is a common problem following stoma formation. The optimal technique for stoma formation is unknown although recent studies have focused on whether placement of prophylactic mesh at stoma formation can reduce PSH rates. The aim of this study was to systematically review use of prophylactic mesh versus no mesh with regard to occurrence of PSH and peristomal complications. Methods A systematic search was performed using PubMed, EmbaseTM and the Cochrane Library to identify randomised controlled trials that analysed placement of prophylactic mesh versus no mesh at time of initial surgery. Meta analysis was performed using random effects methods. Results A total of 506 studies were identified by our search strategy. Of these, 8 studies were included, involving 430 patients (217 mesh vs 213 no mesh). Prophylactic mesh placement resulted in a significantly lower rate of PSH formation (42/217 [19.4%] vs 92/213 [43.2%]) with a combined risk ratio of 0.40 (95% confidence interval [CI]: 0.21-0.75, p=0.004). Placement of prophylactic mesh did not result in increased peristomal complications (15/218 [6.9%] vs 16/227 [7.0%]) with a combined risk ratio of 1.0 (95% CI: 0.49-2.01, p=0.990). Conclusions Prophylactic placement of mesh at primary stoma formation may reduce the incidence of PSH, without an increase in peristomal complications. However, the overall quality of the randomised controlled trials included in the meta-analysis was poor, and should prompt caution regarding the applicability of the findings of the individual studies and the meta-analysis to everyday practice. PMID- 27269440 TI - Parents' experience of undertaking an intensive cognitive orientation to daily occupational performance (CO-OP) group for children with cerebral palsy. AB - PURPOSE: The purpose of this study was to explore the experience of parents of children with cerebral palsy (CP) who participated in an intensive cognitive orientation to daily occupational performance (CO-OP) group program addressing child chosen goals. METHOD: Participants were six parents of children with CP who participated in a CO-OP upper limb task-specific training program. Parents participated in semi-structured interviews conducted via phone. A grounded theory approach was used. Interviews were transcribed verbatim and coded to identify categories and overarching themes of the parent experience of CO-OP. RESULTS: The theory of CO-OP for children with CP was one of offering a unique and motivating learning experience for both the child and the parent, differing from other therapeutic approaches that families had previously been involved in. Five categories were identified: the unique benefits of CO-OP; the importance of intensity; the child's motivation; challenging the parent role; and the benefits and challenges of therapy within a group context. CONCLUSION: Parents felt that CO-OP was a worthwhile intervention that leads to achievement of goals involving upper limb function and had the capacity to be transferred to future goals. Intensity of therapy and a child's motivation were identified as important factors in improvements. Further studies using quantitative research methods are warranted to investigate the benefits of CO-OP for children with neurological conditions. Implications for rehabilitation The cognitive orientation to daily occupational performance (CO-OP) is a promising upper limb cognitive motor training intervention for children with cerebral palsy. In a small sample, parents perceived that CO-OP leads to achievement of upper limb goals. Intensity of therapy, the child's motivation and the parents' ability to "step-back" were identified as important to the success of CO-OP. PMID- 27269441 TI - Measuring the impact of clinically relevant interprofessional education on undergraduate medical and nursing student competencies: A longitudinal mixed methods approach. AB - Interprofessional education (IPE) to improve collaborative competencies is essential for delivering high-quality care. Yet creating clinically relevant IPE and linking it to improvements in behaviours remains challenging, and few objective measurement instruments are available. We developed a process for creating IPE and objective observational tools through collaborative care best practice models (CCBPMs). These models describe the professional and interprofessional behaviours needed for specific patient populations, illnesses, and care settings. Four IPE workshops based on CCBPMs were implemented for all medical and nursing students during their clinical/clerkships years. Students in Cohort 1 completed two IPE workshops: rapid response and end-of-life. For Cohort 2, students completed four IPE workshops, adding chronic paediatric illness and transitions for the cognitively impaired. Valid and reliable collaborative behaviors observational assessment tools (CBOATs) derived from CCBPMs for the rapid response and end-of-life workshops were developed. CBOATs were used in the longitudinal assessment of student learning for both cohorts during two Interprofessional Teamwork Objective Structured Clinical Examinations (ITOSCEs) conducted before and after the students completed the IPE workshops. Over a 2 year period, 457 students completed the IPE simulations and ITOSCEs. Both medical and nursing students demonstrated significant improvement in CBOAT scores. Comparisons between the cohorts showed that participation in four versus two IPE experiences did not significantly improve most CBOAT scores. We conclude that undergraduate IPE simulation experiences based on CCBPMs result in measurable improvements in learner behaviours necessary for effective collaborative and team based practice in specific care areas. PMID- 27269442 TI - Managing the comorbidity of schizophrenia and ADHD. PMID- 27269443 TI - Ni-Catalyzed Carboxylation of Unactivated Alkyl Chlorides with CO2. AB - A catalytic carboxylation of unactivated primary, secondary, and tertiary alkyl chlorides with CO2 at atmospheric pressure is described. This protocol represents the first intermolecular cross-electrophile coupling of unactivated alkyl chlorides, thus leading to new knowledge in the cross-coupling arena. PMID- 27269447 TI - Copper-Catalyzed Trifluoromethylation of Alkenes with Redox-Neutral Remote Amidation of Aldehydes. AB - A room-temperature and one-pot synthesis of epsilon-CF3-substituted amides via the copper-catalyzed trifluoromethylation of alkenes with redox-neutral remote amidation of aldehydes is described. This reaction is featured by an unprecedented 1,5-H atom abstraction from aldehydic C-H bonds by alpha-CF3-alkyl radicals resulting from the radical trifluoromethylation of alkenes, thus enabling a new possibility of the trifluoromethylation-initiated remote sp(2) C-H functionalization. PMID- 27269448 TI - The Aarhus convention in the nuclear sector-right to information versus nonproliferation? AB - Nuclear events and problems in siting procedures of nuclear plants poses problems of timely information and the question of proper and trustful information. This paper is divided into three parts. In the first part, the right to information and the Aarhus convention are analysed. The basic rights of the public in the field of environmental matters are presented and discussed. Such rights are also examined through the case law of the European Court of Human Rights. The second part deals with the problem of possible conflicts between the right to information (and environmental information) and obligations from NPT. The third part proposes some solutions to provide a balance between the obligation of giving information and the obligation of protecting certain information under the NPT. PMID- 27269449 TI - Single-Cell-Arrayed Agarose Chip for in Situ Analysis of Cytotoxicity and Genotoxicity of DNA Cross-Linking Agents. AB - Development of approach or device to allow continuous multiple measurements, such as integrating cytotoxic and genotoxic analysis, is quite appealing for study of the drug's activity and mechanism of action or resistance. In this study, a single-cell-arrayed agarose chip system was developed to combine cell cultivation with subsequent in situ analysis of cytotoxicity and genotoxicity of the chemotherapeutic agent. The modified alkaline comet assay coupled with the Live/Dead assay was used to monitor the interstrand cross-links (ICLs) formation and the cytotoxic effects in different glioma cell lines. In addition, the ICL induced double strand breaks (DSBs) was measured on the chip to reflect the level of ICLs indirectly. Compared with the traditional methods, the microarray agarose device offers higher throughput, reproducibility, and robustness, exhibiting good potential for high-content drug screening. PMID- 27269450 TI - Evolutionary considerations in the development of chronic pelvic pain. AB - Chronic pelvic pain is common among women of reproductive age and is associated with significant morbidity and comorbidities. In this Viewpoint, we explore the evolutionary cause of pelvic pain and summarize evidence that supports a menstruation-related evolutionary cause of chronic visceral pelvic pain: (1) lifetime menstruation has increased; (2) severe dysmenorrhea is common in the chronic pelvic pain population, particularly among those with pain sensitization; and (3) a potential biological mechanism can be identified. Thus, chronic pelvic pain may arise from the mismatch between the slow pace of biological evolution in our bodies and the relatively rapid pace of cultural changes that have resulted in increased menstrual frequency due to earlier menarche, later mortality, and lower fecundity. One possible mechanism that explains the development of persistent pain from repeated episodes of intermittent pain is hyperalgesic priming, a physiological process defined as a long-lasting latent hyperresponsiveness of nociceptors to inflammatory mediators after an inflammatory or neuropathic insult. The repetitive severely painful menstrual episodes may play such a role. From an evolutionary perspective the relatively rapid increase in lifetime menstruation experience in contemporary society may contribute to a mismatch between lifetime menstruation and the physiological pain processes, leading to a maladaptive state of chronic visceral pelvic pain. Our current physiology does not conform to current human needs. PMID- 27269471 TI - Clinicians' views on parental involvement in the treatment of adolescent anorexia nervosa. AB - A questionnaire and in-depth interviews with 20 allied health clinicians generated data on key aspects of family-based treatment for adolescent anorexia nervosa that enhance recovery, processes that engage parents in treatment, and how and why clinicians modify or adapt the manualized Maudsley Family Based Treatment model. Findings indicate that clinicians support key principles in the Maudsley model, but that the approach is not implemented in the full, manualized form. Rather, aspects are integrated with clinicians' own clinical judgements based on assessment of the needs and capacities of families, cultural appropriateness, impact on family dynamics, and gains during early treatment. PMID- 27269473 TI - Refractory angina: new drugs on the block. PMID- 27269472 TI - Subcellular localisation of Theiler's murine encephalomyelitis virus (TMEV) capsid subunit VP1 vis-a-vis host protein Hsp90. AB - The VP1 subunit of the picornavirus capsid is the major antigenic determinant and mediates host cell attachment and virus entry. To investigate the localisation of Theiler's murine encephalomyelitis virus (TMEV) VP1 during infection, a bioinformatics approach was used to predict a surface-exposed, linear epitope region of the protein for subsequent expression and purification. This region, comprising the N-terminal 112 amino acids of the protein, was then used for rabbit immunisation, and the resultant polyclonal antibodies were able to recognise full length VP1 in infected cell lysates by Western blot. Following optimisation, the antibodies were used to investigate the localisation of VP1 in relation to Hsp90 in infected cells by indirect immunofluorescence and confocal microscopy. At 5h post infection, VP1 was distributed diffusely in the cytoplasm with strong perinuclear staining but was absent from the nucleus of all cells analysed. Dual-label immunofluorescence using anti-TMEV VP1 and anti-Hsp90 antibodies indicated that the distribution of both proteins colocalised in the cytoplasm and perinuclear region of infected cells. This is the first report describing the localisation of TMEV VP1 in infected cells, and the antibodies produced provide a valuable tool for investigating the poorly understood mechanisms underlying the early steps of picornavirus assembly. PMID- 27269474 TI - The Influence of On-pump Versus Off-pump Surgery on Short- and Medium-term Postoperative Coronary Flow Reserve After Coronary Artery Bypass Grafting. AB - BACKGROUND: Although several clinical trials have compared surgical outcomes between off-pump and on-pump coronary artery bypass grafting (CABG), whether there is a difference in the early- and medium-term postoperative coronary microvascular functions is not fully understood. We compared short- and medium term coronary microvascular function after off-pump and on-pump CABG. METHODS: A prospective study of patients undergoing off-pump and on-pump CABG. Eighty-two patients scheduled for CABG were recruited: 38 underwent off-pump surgery and 44 on-pump surgery. Each participant's coronary flow reserve (CFR) and diastolic function were measured with transthoracic Doppler echocardiography six and 12 months after surgery. RESULTS: Baseline and hyperaemic diastolic peak flow velocity in the left anterior descending artery were similar in both groups, as was CFR (2.22+/-0.66) in the off-pump group compared with (2.13+/-0.61) in the on pump group, (P=0.54). Coronary flow reserve was significantly and inversely correlated with high sensitivity C-reactive protein concentration (r=-0.416; P<0.001) and positively correlated with mitral E/A-wave velocity ratio (r=0.247; P=0.02). Stepwise linear regression analysis revealed that only high sensitivity C-reactive protein concentration was independently correlated with CFR (beta= 0.272, P=0.02). CONCLUSIONS: Heart-lung bypass technique had no medium-term influence on the coronary microcirculation, despite a possible initial unfavourable effect. Serum hs-CRP concentration was an independent predictor of medium-term coronary microvascular dysfunction. PMID- 27269475 TI - The Aortic Root Replacement Procedure: 12-year Experience from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Database. AB - BACKGROUND: The aortic root replacement procedure (ARR), is often considered the gold standard in the management of aortic root and ascending aorta aneurysms. Our aim was to review the Australian experience with this procedure to ascertain early and late outcomes of mortality and morbidity. METHODS: We reviewed the Australian and New Zealand Society of Cardiac and Thoracic Surgeons' (ANZSCTS) database for patients undergoing ARR. Preoperative, intraoperative and postoperative variables were analysed. Multiple regression was performed to determine independent predictors of 30-day mortality and permanent stroke, and predictors of late death. Survival estimates were obtained by cross-linking the ANZSCTS database with the Australian Institute of Health and Welfare's National Death Index database. RESULTS: Between January 2001 and December 2011, 954 patients underwent ARR with a mean age of 56+/-15.2 years. The overall 30-day mortality was 5.9% (n=56) with a permanent stroke rate of 2.3% (n=21). The elective surgery mortality was 3.6%. Long-term survival was estimated as 84.4% and 68.7% at 5 and 10 years, respectively. CONCLUSIONS: Aortic root replacement surgery reveals acceptable early mortality, low postoperative stroke rates, and acceptable long-term survival. PMID- 27269476 TI - TDDFT screening auxiliary withdrawing group and design the novel D-A-pi-A organic dyes based on indoline dye for highly efficient dye-sensitized solar cells. AB - Based on the experimentally synthesized dye JZ145, we designed a series of novel D-A-pi-A dyes SPL201-SPL211 with different pi-conjugated bridges and a new auxiliary withdrawing group for highly efficient dye-sensitized solar cells (DSSCs) using density functional theory (DFT) and time-dependent DFT(TDDFT). The molecular structures, energy levels, absorption spectra, light-harvesting efficiency (LHE), driving force of injection(DeltaGinj) and regeneration(DeltaGreg), electron dipole moment (MUnormal) and lifetime of the first excited state(tau) were all scrutinized in details. Results reveal that the additional withdrawing group A2 and the pi-conjugated group di-eta-hexyl substituted cyclopentadithiophene (CPDT) are more promising functional groups for the organic dyes with D-A-pi-A structure. We further designed SPL212 and SPL213 by employing indoline group as donor, the above screened functional groups as pi conjugated bridge and additional withdrawing group, biscarbodithiolic acid and dicyanovinyl sulfonic acid groups as acceptor group. We found that SPL212 exhibits not only a higher molar extinction coefficient with an increment of 30.8%, larger excited state lifetime and an obvious redshift of 201nm but also a broader absorption spectrum covering the entire visible range even up to near-IR of 1200nm compared to JZ145. So, SPL212 can be used as a promising candidate for DSSCs. In addition, the results also prove that biscarbodithiolic acid may be more favorable than dicyanovinylsulfonic acid as acceptor group in DSSCs. PMID- 27269477 TI - Ethanol and Water Adsorption on Transition-Metal 13-Atom Clusters: A Density Functional Theory Investigation within van der Waals Corrections. AB - Transition-metal (TM) nanoparticles supported on oxides or carbon black have attracted much attention as potential catalysts for ethanol steam reforming reactions for hydrogen production. To improve the performance of nanocatalysts, a fundamental understanding of the interaction mechanism between water and ethanol with finite TM particles is required. In this article, we employed first principles density functional theory with van der Waals (vdW) corrections to investigate the interaction of ethanol and water with TM13 clusters, where TM = Ni, Cu, Pd, Ag, Pt, and Au. We found that both water and ethanol bind via the anionic O atom to onefold TM sites, while at higher-energy structures, ethanol binds also via the H atom from the CH2 group to the TM sites, which can play an important role at real catalysts. The putative global minimum TM13 configurations are only slightly affected upon the adsorption of water or ethanol; however, for few systems, the compact higher-energy icosahedron structure changes its configuration upon ethanol or water adsorption. That is, those configurations are only shallow local minimums in the phase space. Except few deviations, we found similar trends for the magnitude of the adsorption energies of water and ethanol, that is, Ni13 > Pt13 > Pd13 and Cu13 > Au13 > Ag13, which is enhanced by the addition of the vdW correction (i.e., from 4% to 62%); however, the trend is the same. We found that the magnitude of the adsorption energy increases by shifting the center of gravity of the d-states toward the highest occupied molecular orbital. On the basis of the Mulliken and Hirshfeld charge analysis, as well as electron density differences, we identified the location of the charge redistribution and a tiny charge transfer (from 0.01 e to 0.19 e) from the molecules to the TM13 clusters. Our vibrational analysis indicates the red shifts in the OH modes upon binding of both water and ethanol molecules to the TM13 clusters, suggesting a weakening of the O-H bonding. PMID- 27269478 TI - Cortical thickness and surface area correlates with cognitive dysfunction among first-episode psychosis patients. AB - BACKGROUND: In studies using magnetic resonance imaging (MRI), some have reported specific brain structure-function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS). METHOD: Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by vertex whole-brain MRI analysis of 63 FEP patients and 30 CS. RESULTS: Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS. CONCLUSIONS: Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure-function relationship in FEP patients compared with CS. PMID- 27269479 TI - Low methylation rates of dopamine receptor D2 gene promoter sites in Japanese schizophrenia subjects. AB - OBJECTIVES: According to the dopamine hypothesis, several studies on the gene for the dopamine receptor D2 (DRD2) have been conducted. However, no trait biomarkers on DRD2 are available. We examined whether the methylation rates in the upstream region of DRD2 in leukocytes are different in schizophrenia (SCZ) subjects compared to control subjects. METHODS: We selected seven CpG sites in the upstream region of DRD2 that may theoretically bind major transcription factors. The methylation rates in these regions of 50 medicated and 18 drug-naive SCZ subjects were compared with those of age-matched control subjects. RESULTS: The methylation rates were significantly lower in medicated (CpG2, P < 0.0001; CpG4, P = 0.013; CpG7, P < 0.0001; and average: 12.9 +/- 1.8 vs. 14.1 +/- 2.2, P = 0.005) and drug-naive SCZ subjects (CpG1, P = 0.006; CpG2, P = 0.001; CpG3, P = 0.001; CpG5, P = 0.02; CpG6, P = 0.015; CpG7, P = 0.027; and average: 9.86 +/- 0.9 vs. 11.2 +/- 1.3, P = 0.002). CONCLUSIONS: We confirmed low methylation rates in the upstream region of DRD2 in both medicated and drug-naive SCZ subjects. Low methylation rates of DRD2 in leukocytes may be a trait biomarker for SCZ. PMID- 27269480 TI - The role of surgery in recurrent endometrial cancer. AB - INTRODUCTION: Endometrial cancer is a common gynecologic malignancy in the United States, and the recurrence rate depends on the disease stage at diagnosis. Recurrence can affect several areas and follow different patterns. AREAS COVERED: The role of surgery at the time of recurrence is not clearly defined. In this review, we fully describe the current evidence available. In particular, we describe how surgical treatment might be recommended for 1) vaginal or pelvic recurrences; 2) retroperitoneal or localized intra-abdominal recurrence, when a maximal cytoreductive effort is more likely to be successful; or 3) isolated distant recurrences when microscopically tumor-free margins can be achieved. Expert commentary: Cases should be evaluated individually, considering factors such as comorbidities, risks of intervention, and impact of treatment on quality of life. PMID- 27269481 TI - Evolution of prostate biopsy techniques. Looking back on a meaningful journey. AB - BACKGROUND: The technique of prostate biopsy has evolved a long way since its inception to being a safe diagnostic procedure. The principles of the biopsy technique continue to improvise with the knowledge about prostate cancer and availability of newer treatment options like active surveillance and focal therapy. Currently, we depend on accurate cancer information from the biopsy more than ever for deciding the ideal treatment option. AIM: The aim of this review is to present the major milestones in prostate biopsy technique evolutions and its impact on the prostate cancer management. ACQUISITION OF EVIDENCE: We performed a detailed non-systematic literature review to present the historical facts on the transformations in prostate biopsy techniques and also the direction of present research to improve accurate cancer detection. SUMMARY OF EVIDENCE: There is a clear change in trend in biopsy technique before and after the introduction of transrectal ultrasound and prostate specific antigen. In the earlier era, the biopsies were aimed at palpable nodules and obtaining adequate prostatic tissue for diagnosis while the later era has moved towards detection of non-palpable and early prostate cancer. Recently, there is an increasing trend towards image guided targeted biopsies to extract maximum cancer information from minimum biopsy cores. CONCLUSION: Prostate biopsy techniques have seen major changes since its inception and have a major impact on prostate cancer management. There is a great potential for research which can further support the newer treatment options like focal therapy. PMID- 27269482 TI - Joint Modeling of Ability and Differential Speed Using Responses and Response Times. AB - With computerized testing, it is possible to record both the responses of test takers to test questions (i.e., items) and the amount of time spent by a test taker in responding to each question. Various models have been proposed that take into account both test-taker ability and working speed, with the many models assuming a constant working speed throughout the test. The constant working speed assumption may be inappropriate for various reasons. For example, a test taker may need to adjust the pace due to time mismanagement, or a test taker who started out working too fast may reduce the working speed to improve accuracy. A model is proposed here that allows for variable working speed. An illustration of the model using the Amsterdam Chess Test data is provided. PMID- 27269486 TI - Racial Difference in Response to Vitamin D Supplementation. AB - This manuscript is the result of work supported by the use of resources and facilities at the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, specifically, the Geriatric Research Education and Clinical Center (GRECC). BACKGROUND: Deficiency in 25-hydroxyvitamin D (25[OH]D) is common, especially in the elderly and African Americans (AA). While 25(OH) D deficiency is associated with multiple negative health outcomes, current recommendations for supplementation of this deficiency may be insufficient. OBJECTIVE: To determine the prevalence of 25(OH)D deficiency, the extent of vitamin D supplementation, and the effect of supplementation on 25(OH) D levels in an elderly Veteran population. The study also focused specifically on the role of race in the risk for 25(OH)D deficiency and in the response to vitamin D supplementation. METHODS: A retrospective chart review was conducted of information including 25(OH)D serum levels pre and post-supplementation, race, and vitamin D supplementation. Subjects were community-dwelling Veterans (>=60years) followed by a VA geriatric clinic. A total of 234 charts were reviewed (124 Caucasian, 78 AA, 32 other/unknown race). Information collected through the chart review was analyzed by comparing the means of 25(OH)D levels pre and post-supplementation across races and across times. RESULTS: At Baseline 206 subjects (88%) were 25(OH)D deficient (<32ng/ml). While 80.6% of them were supplemented, only 10.24% (17 of 166) achieved normal 25(OH)D serum levels. AAs (n=78) had significantly lower Baseline levels compared to Caucasians (n=124) and differences were consistent across time. Fewer AAs than Caucasians increased to normal (AA:6.3%; Caucasian:12.8%). CONCLUSIONS: Conservative oral vitamin D supplementation is largely ineffective at achieving therapeutic serum levels, especially for AAs. Future research is needed to focus on individualized supplementation strategies and targeted risk factors such as race. PMID- 27269485 TI - Patient- and Family-Centered Care as an approach to reducing disparities in asthma outcomes in urban African American children: A review of the literature. AB - We thank Cathy Eames (Director, Library Services, Detroit Medical Center) for valuable input and assistance with the search strategy. Funding for this research was supported by a grant from Children's Hospital of Michigan Research Foundation (Principal Investigator: Terrance L. Albrecht, Ph.D.). BACKGROUND: Patient- and family-centered care (PFCC) has the potential to address disparities in access and quality of healthcare for African American pediatric asthma patients by accommodating and responding to the individual needs of patients and families. STUDY OBJECTIVES: To identify and evaluate research on the impact of family provider interventions that reflect elements of PFCC on reducing disparities in the provision, access, quality, and use of healthcare services for African American pediatric asthma patients. METHODS: Electronic searches were conducted using PubMed, CINAHL, and Psyclnfo databases. Inclusion criteria were peer reviewed, English-language articles on family-provider interventions that (a) reflected one or more elements of PFCC and (b) addressed healthcare disparities in urban African American pediatric asthma patients (<=18years). RESULTS: Thirteen interventions or programs were identified and reviewed. Designs included randomized clinical trials, controlled clinical trials, pre- and post interventions, and program evaluations. CONCLUSIONS: Few interventions were identified as explicitly providing PFCC in a pediatric asthma context, possibly because of a lack of consensus on what constitutes PFCC in practice. Some studies have demonstrated that PFCC improves satisfaction and communication during clinical interactions. More empirical research is needed to understand whether PFCC interventions reduce care disparities and improve the provision, access, and quality of asthma healthcare for urban African American children. ELECTRONIC DATABASES USED: PubMed, CINAHL, and Psyclnfo ABBREVIATIONS: AA-African American: CCT-Controlled clinical trial; ED-Emergency Department; ETS-Environmental tobacco smoke; FCC- Family Centered Care; PFCC-Patient and Family Centered Care; RCT- Randomized, controlled trial. PMID- 27269487 TI - Cultural and Cognitive Determinants of Personal Control in Older African Americans with Diabetes. AB - ACKNOWLEDGEMENTS: The study was funded by Pennsylvania Department of Health's Commonwealth Universal Research Enhancement (CURE) Program (SAP#4100051727). OBJECTIVE: To describe the determinants of personal control over diabetes complications in older African Americans (N=123) with type 2 diabetes. METHODS: We administered structured instruments to assess perceptions of personal control, time orientation, religiosity, depression, and cognition in this cross-sectional study. RESULTS: More years of education (p <= .001), better Clock Drawing (p <= .001), higher levels of Religiosity (p <= .04), and lower Present Time Orientation (p <= .01 ) were independent predictors of higher levels of Personal Control. DISCUSSION: Risk perceptions of control over diabetes complications vary among older African Americans according to cultural constructs, executive function, and education. This finding highlights the cultural diversity in this population and the potential impact of culturally-determined views and cognitive function on health behaviors. Cognitive screening of older persons with diabetes and interventions that incorporate perceptions of time and religion to increase rates of eye examinations are needed. PMID- 27269488 TI - Prostate Cancer Screening and Mortality in Blacks and Whites: A Hospital-based Case-Control Study. AB - BACKGROUND: Prostate cancer incidence and mortality are substantially higher in Black than in white men. Prostate cancer screening remains controversial. This study was conducted to assess the impact of, and racial differences in, prostate cancer screening on prostate cancer mortality. METHODS: This was a case-control study of Black and White men in eight hospitals. Cases were deaths related to prostate cancer; controls were hospital-based subjects that were frequency matched to cases based on age and race. Multivariable logistic regression was used to test the association between screening and prostate cancer mortality. RESULTS: Cases had fewer PSA (prostate-specific antigen) tests than controls (1.73 vs. 3.98, p<0.001). White controls had higher rates of PSA tests than other sub-groups. There was no difference in PSA testing between Black cases and controls. Mean co-morbidity was 10.3 in cases and 2.63 in controls. Prostate cancer mortality was 55 to 57% lower among the screened persons. Individuals who died of prostate cancer related causes were less likely to have received PSA testing (OR=0.65; 95% Cl 0.56-0.75). CONCLUSIONS: The odds of dying from prostate cancer were lower among white men receiving screening tests. Having less co morbidity was associated with lower odds of mortality in both races. This study raises the possibility that screening for prostate cancer with the PSA test may be more effective in white than in Black men. PMID- 27269489 TI - Headache in African Americans: An Overlooked Disparity. AB - PURPOSE: The persistence of health disparities in the U.S. has necessitated additional research on race-related health disparities among Americans. Remarkably little research has examined race differences in persons with headache disorders, even though 45 million Americans experience episodic or chronic headaches annually. This review paper examined peer-reviewed publication to examine potential race differences in persons with headache disorders in the areas of headache epidemiology, headache characteristics, psychiatric comorbidity, treatment utilization, and treatment outcomes. PROCEDURES: A multi database search (PubMed, Web of Science, PsychlNFO) identified U.S. studies that enrolled racially diverse samples of persons with headache disorders and qualitatively examined potential race-related disparities. MAIN FINDINGS: Compared to their Caucasian counterparts, African American headache patients are more likely to (i) be diagnosed with comorbid depressive disorders; (ii) report headaches that are more frequent and severe in nature, (iii) have their headaches under-diagnosed and/or undertreated; and (iv) discontinue treatment prematurely, regardless of socioeconomic status. PRINCIPAL CONCLUSIONS: State of the science treatments for chronic headaches are efficacious; unfortunately, race-related disparities prevent African American headache patients from benefiting from these treatments. Research is needed that enables African Americans with severe headaches to access current headache treatments to alleviate headache burden on the African American community. PMID- 27269490 TI - Access matters: Improved detection of premalignant polyps with a screening colonoscopy program for the uninsured. AB - BACKGROUND: Colonoscopy is an effective screening modality for the early detection of colonic polyps and cancer, but screening rates are low particularly among minorities and the uninsured. In 2008, Capital Health obtained a clinical grant from the American Cancer Society to perform screening colonoscopies for patients without insurance who were established at the hospital's primary care clinic. The aim of this study is to evaluate the grant program with respect to endoscopic findings and changes in the demographics of patients undergoing colonoscopy. METHODS: A retrospective review was performed on all patients registered for colonoscopy at the endoscopy suite of Capital Health Regional Medical Center. A pre- and postimplementation analysis was designed to compare 3 groups: 1) all colonoscopies performed in the twenty four months prior to the program's start (pre-program group) 2) all screening colonoscopies performed on uninsured patients in the program during twenty four months period (program group) and 3) all other colonoscopies performed in the same suite during the time of the program (parallel group). A descriptive analysis of demographics, ethnicity and insurance status was performed. RESULTS: There were a total of 4004 colonoscopies performed during this 52month period, 53 (1.3%) were excluded because the data was incomplete. The pre-program group had 1892 colonoscopies of which 375 were screening colonoscopies, the program group had 363 screening colonoscopies, and the parallel group had 1750 colonoscopies of which 343 were screening colonoscopies. Implementation of the grant program resulted in nearly double the screening colonoscopies performed as compared to the pre-program period (375 vs 705). There was no change in the number of the reimbursed procedures performed in the same suite after initiation of the grant program. The proportion of minority patients undergoing a screening procedure in the program group was significantly increased compared to the other groups and this increase was largely accounted for by a higher proportion of Hispanic patients. The number of patients with polyps was higher in the program group compared with the preprogram and parallel group (42%, 36.8%, and 33.9%, respectively). CONCLUSIONS: A grant-funded program offering screening colonoscopies to uninsured patients demonstrated a high number of premalignant polyps that might otherwise have been undetected. Our experience suggests that targeting health care disparities by insurance status can increase access to preventive services and detect a high number of premalignant lesions. PMID- 27269491 TI - Psychiatric Medication, African Americans and the Paradox of Mistrust. AB - OBJECTIVES: To examine race differences in how generalized mistrust, mistrust in physicians, and mistrust in psychiatric medication shape the willingness to utilize psychiatric medication. METHODS: Data was used from two waves (1998 and 2006) of the U.S. General Social Survey a representative sample of non institutionalized Americans. We analyzed data for 343 African American and 1,920 white adults, ages 18-89. The data included measures of the respondents' willingness to utilize psychiatric medication as well as measures of generalized mistrust, mistrust in physicians, and mistrust in psychiatric medication. We employed ordinary least squares regression to test whether these three forms of mistrust reduce the black-white gap in psychiatric drug usage and whether race moderates the association between any type of mistrust and the willingness to endorse psychiatric medication utilization. RESULTS: Mistrust in physicians and psychiatric medication is related to less willingness to utilize psychiatric medicines for both African Americans and whites; however, paradoxically, these forms of mistrust decrease psychiatric drug usage more steeply for whites. CONCLUSIONS: The pattern of findings in this study suggests that trust or low levels of mistrust, rather than high levels of mistrust, actually maintains the black-white difference in the use of psychiatric medication. PMID- 27269492 TI - They Cannot Hear, Talk, and See in Sensible Ways: The Impact of Personality Disorders on HIV and other Sexually Transmitted Infections. PMID- 27269493 TI - Parent & Family Influences on Adopting Healthy Weight-Related Behaviors: Views and Perceptions of Obese African-American Female Adolescents. AB - RTI International is acknowledged for supporting the time of Susan McRitchie, Keeley Pratt and Susan Sumner to participate in the design, execution, or analysis of this study. East Carolina University would like to acknowledge Brittney France for being a triangulated investigator for the qualitative analysis and to the Pitt Memorial Hospital Foundation for financial support of the healthy lifestyles camp. Our purpose was to evaluate the views of obese African-American (AA) female adolescents concerning parent and family factors relating to obesity and a healthy lifestyle. Obese AA female adolescents enrolled in a residential healthy lifestyle program completed inventories measuring family functioning and perceptions of parenting styles, and participated in focus groups to identify themes regarding parent and family involvement in healthy lifestyle change. The majority of participants' mothers were scored as "inductive/authoritative" and fathers were "indulgent". Mothers reportedly were seen as more likely to encourage dieting to control weight than fathers. Common themes of the focus groups included a desire for family involvement, identification of family behaviors that were supportive as well as those which were perceived as unhelpful. Though generalizability of these results is limited by a homogenous small sample size, our results suggest that obese adolescents seeking weight loss treatment desire significant family involvement in their efforts. PMID- 27269494 TI - Factors Associated with Human Papillomavirus Vaccine Acceptance Among Haitian and African-American parents of Adolescent Sons. AB - ACKNOWLEDGEMENTS: The authors would like to thank Cecilia Marquez, Justine Lavoye, Elaine Shu and Hailey Tipton for their efforts with participant recruitment and data collection. OBJECTIVE: To assess knowledge, attitudes, beliefs and practices related to HPV vaccination among African-Americans and Haitian immigrant parents, and to compare vaccination rates of their sons. STUDY DESIGN: We performed semi-structured interviews with parents of boys aged 11-17 who had not yet received the HPV vaccine. We used validated surveys of HPV knowledge, trust in physicians, and intention to vaccinate. We probed participants' thought processes about HPV vaccination, and examined parental attitudes, beliefs, and practices toward HPV vaccination using open-ended questions. We then reviewed medical records to determine whether sons were subsequently vaccinated. RESULTS: 25 African-American and 30 Haitian immigrant parents and legal guardians participated in the study. Haitian immigrants were more likely to be married and to practice a religion than African-Americans. Both groups had limited knowledge of HPV (32% of questions were answered correctly by Haitian immigrants vs. 31% by African-Americans). Sixty-four percent of African Americans and 79% of Haitians intended to vaccinate their sons, however only 24% of African-American and 20% of Haitian sons received vaccination within 12 months of the interview. Open-ended questions revealed that most African-Americans felt that vaccination fell within the parental role, while some Haitian immigrants felt uncomfortable vaccinating against sexually transmitted infections because they felt children should not be having sex. Both groups wanted more information about HPV vaccines. CONCLUSIONS: Improving HPV vaccine rates in Haitian and African-American boys may require culturally competent approaches that address ethnic-specific barriers among their parents. PMID- 27269495 TI - The Association of Clinician Characteristics with their Attitudes Toward Patients with Sickle Cell Disease: Secondary Analyses of a Randomized Controlled Trial. AB - BACKGROUND: A high level of evidence exists to suggest that negative attitudes held by clinicians toward persons with sickle cell disease serve as important barriers to the delivery of high quality care to this patient population. Little is known, though, about the characteristics of clinicians that may be predictive of these negative attitudes. METHODS: During spring and summer 2009, we conducted a randomized controlled trial to test an intervention to improve clinician attitudes toward persons with sickle cell disease. Participating clinicians completed questionnaires regarding their demographic characteristics and their attitudes toward sickle cell patients. Principal clinician characteristics of interest included their race, professional discipline (nurse/physician), and the amount of their recent exposure to sickle cell patients in pain. Secondary analyses from this trial are presented here. MAIN FINDINGS: Asian clinicians reported more negative attitudes towards these patients than did Black or White clinicians, nurses reported more negative attitudes than physicians, and clinicians with the greatest levels of recent exposure to sickle cell patients in pain reported more negative attitudes than did clinicians with lower levels of recent exposure. CONCLUSIONS: Our findings could facilitate the development of tailored educational resources needed to improve the quality of care delivered to persons with sickle cell disease, a national priority for sickle cell efforts. PMID- 27269496 TI - Combining Community-Based Participatory Research (CBPR) with a Random-Sample Survey to Assess Smoking Prevalence in an Under-Served Community. AB - ACKNOWLEDGMENTS: The authors would like to thank Laura McClure for her help with the manuscript submission, the Liberty City Community Health Advisory Board for its collaboration on this study, as well as the survey interviewers, and the survey participants. INTRODUCTION: Underserved communities might lag behind Healthy People 2010 objectives of smoking reduction because of smoking behavior disparities. This possibility was investigated through a random-sample survey conducted in a disenfranchised community in Miami-Dade County, Florida, using a Community-Based Participatory Research (CBPR) framework. The survey was triggered by our finding that this community had higher than expected incidence of tobacco associated cancers. METHODS: Survey methods, resulting from a dialog between the Community Advisory Board and academic researchers, included: (a) surveying adult residents of a public housing complex located within the community; (b) probability sampling; (c) face-to-face interviews administered by trained community residents. 250 households were sampled from 750 addresses provided by the county Public Housing Agency. The completed surveys were reviewed by the academic team, yielding 204 questionnaires for the current analysis. RESULTS: Of the 204 respondents, 38% were current smokers. They estimated the percentages of smokers in their household and among their five best friends at 33% and 42%, respectively, and among adults and youth in the community at 72% and 53%, respectively. CONCLUSIONS: A mix of state-of-art methodology with CBPR principles is seldom encountered in the current literature. It allowed the research team to find a high smoking prevalence in an underserved community, twice the statewide and nationwide estimates. Similar or higher levels of smoking were perceived in respondent's entourage. Such disparity in smoking behavior, unlikely to result from self-selection bias because of our rigorous methodology, calls for community specific tobacco control efforts commensurate to the magnitude of the problem. PMID- 27269497 TI - Hydroxyurea therapy in sickle cell disease: An alternative approach to preoperative red cell transfusion. PMID- 27269498 TI - Insurance Eligibility of Adult Emergency Department Patients. AB - ACKNOWLEDGMENTS: This study was supported by a grant from the Maryland Emergency Medicine Network. The manuscript was copyedited by Linda J. Kesselring, M.S., ELS, the technical editor/writer in the Department of Emergency Medicine at the University of Maryland School of Medicine. PURPOSE: To determine if uninsured patients seeking care in an inner-city emergency department (ED) were eligible for any of the three government-sponsored insurance programs that were available to them at the time this study was conducted. METHODS: In June and July 2012 (before implementation of the Affordable Care Act), a medical student and two social work students trained in insurance eligibility approached a convenience sample of uninsured adult ED patients (age >=19years) whose conditions warranted discharge after treatment. The students administered a survey that collected information (age, marital status, income, family size, number of dependents, and pregnancy status) that was used to determine if the patient was eligible for medical insurance. Patients who were acutely ill, confused, under the influence of substances, acutely psychotic, non-English speaking, unable to give consent, under arrest, or being admitted or transferred were deemed ineligible for this study. RESULTS: Of the 132 patients who participated in the study, 114 (86.4%) were eligible for insurance. The difference between the median incomes for those who were eligible for insurance and those who were not ($2,300 vs $17,388) was statistically significant (p<0.0001). CONCLUSION: EDs have a valuable opportunity to identify patients who are eligible for government-backed medical insurance programs. Identifying these individuals, and assisting them with the application process, has the potential to enhance the indigent population's access to medical care and to give hospitals a means of billing for reimbursement for services provided. PMID- 27269499 TI - Misdiagnosis in a 12 Year-Old Female with Right Aberrant Subclavian Artery and Difficult Swallowing. AB - ACKNOWLEDGEMENTS: Steven Do, Portia Daniels, David T. Nelson, UCLA Radiology Media Center. PMID- 27269500 TI - Inauguration Address of Wayne A. I. Frederick, 17th President of Howard University, March 6, 2015. PMID- 27269502 TI - Ocular syphilis in patients with Human Immunodeficiency Virus infection. AB - As Acquired Immunodeficiency Disease (AIDS) turns thirty-years old, much progress has been made. 56,000 new cases of the Human Immunodeficiency Virus (HIV) infection are expected in Americans this year. At least half or more will be in African Americans. Reports of the association between syphilis and HIV infection are well documented. We present a case of bilateral optic neuritis and panuveitis as the initial presentation in a previously undiagnosed patient with human immunodeficiency virus (HIV) and syphilis. PMID- 27269503 TI - Protective Role of Hinokitiol Against H2O2-Induced Injury in Human Corneal Epithelium. AB - PURPOSE: We recently found that hinokitiol has anti-inflammatory activity in human corneal epithelial (HCE) cells. Herein, we investigated the protective role of hinokitiol against H2O2-induced injury in HCE cells and the mechanisms that underlie its action. METHODS: HCE cells were incubated with different concentrations of hinokitiol or dimethylsulfoxide (DMSO), which served as a vehicle control, before H2O2 stimulus. The cell viability was evaluated using a cell counting kit-8 (CCK-8) assay. TUNEL, phosphorylated histone gammaH2A.X, cleaved caspase-3 expression analyses, and location of cytochrome c were conducted to detect cell injury and apoptosis. Reactive oxygen species (ROS), catalase (CAT), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), and total antioxidative capacity (T-AOC) were used to determine oxidative stress. Bcl-2 and Bax protein expressions were measured by western blotting. RESULTS: Hinokitiol significantly improved the cell viability, decreased the apoptosis rate, inhibited DNA damage, and reduced cleaved caspase-3 expression and the leakage of cytochrome c from mimitochondrion to cytoplasm of HCE cells against the oxidative stress induced by H2O2. Generation of ROS and MDA and decreased activity of CAT, SOD, and T-AOC were also ameliorated by hinokitiol administration. Moreover, Bcl-2 expression was down-regulated while Bax was up regulated by H2O2 stimulus, which were reversed by hinokitiol application. CONCLUSION: Hinokitiol protects HCE cells against H2O2-induced injury likely by its antioxidant activity and modulating the Bcl-2 signaling pathway. PMID- 27269504 TI - Physicochemical characterisation and antimicrobial phototoxicity of an anionic porphyrin in natural deep eutectic solvents. AB - Natural deep eutectic solvents (NADES) are a newly discovered group of eutectics which has shown promise as a solvent in antimicrobial photodynamic therapy (aPDT). The purpose of this study was to investigate preparations of an anionic porphyrin, meso-tetra-(4-carboxyphenyl)-porphine (TCPP), solubilised in NADES, with regard to their physicochemical and antibacterial properties. The NADES CS (pH~0), ChX (pH~4) and MFG (pH~1) solubilised TCPP with absorption maximum ~443nm and emission maximum ~678nm, indicating formation of the TCPP dication. Dilution of TCPP-NADES>1:1 (water) reduced the physical stability of the preparations. The photostability half-lives of TCPP in methanol, MFG, and CS were ~9h, 6.9h and 3.2h, respectively. Nanomolar concentrations of TCPP solubilised in diluted MFG combined with ?27J/cm(2) blue light increased Gram-positive and Gram-negative bacterial phototoxicity, >99.98% and 96% bacterial reduction, respectively, compared to TCPP in PBS/ethanol under equivalent treatment conditions. TCPP solubilised in diluted CS was toxic to bacteria both in the absence (36-72% reduction) and presence of light. TCPP in CS, and in the CS component citric acid, induced a TCPP-concentration dependent increase in Gram-negative phototoxicity relative to controls, which was most pronounced for TCPP-CS. The mechanism behind the increased toxicity is unknown. PMID- 27269505 TI - RNA-stable isotope probing: from carbon flow within key microbiota to targeted transcriptomes. AB - Stable isotope probing of RNA has enthused researchers right from its first introduction in 2002. The concept of a labelling-based detection of process targeted microbes independent of cellular replication or growth has allowed for a much more direct handle on functionally relevant microbiota than by labelling of other biomarkers. This has led to a widespread application of the technology, and breakthroughs in our understanding of carbon flow in natural microbiomes, autotrophic and heterotrophic physiologies, microbial food webs, host-microbe interactions and environmental biotechnology. Recent studies detecting labelled mRNA demonstrate that RNA-SIP is not limited to the analysis of rRNA, but is currently developing towards an approach for accessing targeted transcriptomes. In combination with next-generation sequencing and other methodological advances, RNA-SIP will continue to deliver invaluable insights into the functioning of microbial communities. PMID- 27269506 TI - Attachment in medical care: A review of the interpersonal model in chronic disease management. AB - Objective Patient-physician interaction is continually examined in an era prioritizing patient-centered approaches, yet elaboration beyond aspects of communication and empathy is lacking. Major chronic conditions would benefit tremendously from understanding interpersonal aspects of patient-physician encounters. This review intends to provide a concise introduction to the interpersonal model of attachment theory and how it informs both the patient physician interaction and medical outcomes in chronic care. Methods A narrative review of the theoretical, neurobiological, epidemiological, investigational, and clinical literature on attachment theory and its impact on medical outcomes was conducted, utilizing a variety of key words as searched on PubMed database. Studies and reviews included were of a variety of sources, including textbooks and peer-reviewed journals. Reports in languages other than English were excluded. Results Measurable, discrete attachment styles and behavioral patterns correlate with poor medical outcomes, including nonadherence in insecure dismissing attachment and care overutilization in insecure preoccupied attachment. Furthermore, insecure dismissing attachment is associated with significant mortality. These variables can be easily assessed, and their effects are reversible, as evidenced by collaborative care outcome data. Discussion Attachment theory is useful a model with application in clinical and investigational aspects of chronic illness care. Implications and guidelines are explored. PMID- 27269507 TI - Intimacy Behaviors and Relationship Satisfaction for Cohabitors: Intimate Sacrifices Are Not Always Beneficial. AB - Guided by interdependence theory, the authors examined how relationship satisfaction is explained by intimate behavior sacrifices in a sample of cohabitors (N = 200). Specifically, it was predicted that characteristics of intimate behavior sacrifices, such as ease and partner appreciation should alter the association of sacrifice frequency and relationship satisfaction. The pattern that emerged demonstrates lower satisfaction for cohabitors when they frequently made intimate sacrifices and their partners were less appreciative of the sacrifices. When making frequent, but less appreciated, intimacy sacrifices for their partner, cohabitors may struggle with intimacy behaviors that are partner oriented. PMID- 27269508 TI - Biracial perception in black and white: How Black and White perceivers respond to phenotype and racial identity cues. AB - OBJECTIVES: This study investigates how racial identity and phenotypicality (i.e., racial ambiguity) shape the perception of biracial individuals in both White and Black perceivers. We investigated complex racial categorization and its downstream consequences, such as perceptions of discrimination. METHOD: We manipulated racial phenotypicality (Black or racially ambiguous) and racial identity (Black or biracial) to test these cues' influence on Black and White race categorizations in a sample of both White (n = 145) and Black (n = 152) identified individuals. RESULTS: Though racial identity and phenotypicality information influenced deliberate racial categorization, White and Black participants used the cues in different ways. For White perceivers, racial identity and phenotypicality additively influenced Black categorization. For Black perceivers, however, racial identity was only used in Black categorization when racial ambiguity was high. Perceived discrimination was related to White (but not Black) perceivers' distribution of minority resources to targets, however Black categorization related to perceived discrimination for Black perceivers only. CONCLUSION: By demonstrating how Black and White individuals use identity and phenotype information in race perceptions, we provide a more complete view of the complexities of racial categorization and its downstream consequences. (PsycINFO Database Record PMID- 27269510 TI - Action of Multiple Cell Wall-Degrading Enzymes Is Required for Elicitation of Innate Immune Responses During Xanthomonas oryzae pv. oryzae Infection in Rice. AB - Xanthomonas oryzae pv. oryzae secretes a number of plant cell wall-degrading enzymes (CWDEs) whose purified preparations induce defense responses in rice. These defense responses are suppressed by X. oryzae pv. oryzae using type 3 secretion system (T3SS) effectors and a type 3 secretion system mutant (T3SS(-)) of X. oryzae pv. oryzae is an inducer of rice defense responses. We assessed the role of individual CWDEs in induction of rice defense responses during infection, by mutating them in the genetic background of a T3SS(-). We mutated the genes for five different plant CWDEs secreted by X. oryzae pv. oryzae, including two cellulases (clsA and cbsA), one xylanase (xyn), one pectinase (pglA), and an esterase (lipA), singly in a T3SS(-) background. We have demonstrated that, as compared with a T3SS(-) of X. oryzae pv. oryzae, a cbsA(-)T3SS(-), a clsA(-)T3SS( ), and a xyn(-)T3SS(-) are deficient in induction of rice immune responses such as callose deposits and programmed cell death. In comparison, a lipA(-) T3SS(-) and a pglA(-)T3SS(-) is as efficient in induction of host defense responses as a T3SS(-). Overall, these results indicate that the collective action of X. oryzae pv. oryzae-secreted ClsA, CbsA, and Xyn proteins is required for induction of rice defense responses during infection. PMID- 27269509 TI - Arabidopsis Proline Dehydrogenase Contributes to Flagellin-Mediated PAMP Triggered Immunity by Affecting RBOHD. AB - Plants activate different defense systems to counteract the attack of microbial pathogens. Among them, the recognition of conserved microbial- or pathogen associated molecular patterns (MAMPs or PAMPs) by pattern-recognition receptors stimulates MAMP- or PAMP-triggered immunity (PTI). In recent years, the elicitors, receptors, and signaling pathways leading to PTI have been extensively studied. However, the contribution of organelles to this program deserves further characterization. Here, we studied how processes altering the mitochondrial electron transport chain (mETC) influence PTI establishment. With particular emphasis, we evaluated the effect of proline dehydrogenase (ProDH), an enzyme that can load electrons into the mETC and regulate the cellular redox state. We found that mETC uncouplers (antimycin or rotenone) and manganese superoxide dismutase deficiency impair flg22-induced responses such as accumulation of reactive oxygen species (ROS) and bacterial growth limitation. ProDH mutants also reduce these defenses, decreasing callose deposition as well. Using ProDH inhibitors and ProDH inducers (exogenous Pro treatment), we showed that this enzyme modulates the generation of ROS by the plasma membrane respiratory burst NADPH oxidase homolog D. In this way, we contribute to the understanding of mitochondrial activities influencing early and late PTI responses and the coordination of the redox-associated mitochondrial enzyme ProDH with defense events initiated at the plasma membrane. PMID- 27269511 TI - Symbiotic Burkholderia Species Show Diverse Arrangements of nif/fix and nod Genes and Lack Typical High-Affinity Cytochrome cbb3 Oxidase Genes. AB - Genome analysis of fourteen mimosoid and four papilionoid beta-rhizobia together with fourteen reference alpha-rhizobia for both nodulation (nod) and nitrogen fixing (nif/fix) genes has shown phylogenetic congruence between 16S rRNA/MLSA (combined 16S rRNA gene sequencing and multilocus sequence analysis) and nif/fix genes, indicating a free-living diazotrophic ancestry of the beta-rhizobia. However, deeper genomic analysis revealed a complex symbiosis acquisition history in the beta-rhizobia that clearly separates the mimosoid and papilionoid nodulating groups. Mimosoid-nodulating beta-rhizobia have nod genes tightly clustered in the nodBCIJHASU operon, whereas papilionoid-nodulating Burkholderia have nodUSDABC and nodIJ genes, although their arrangement is not canonical because the nod genes are subdivided by the insertion of nif and other genes. Furthermore, the papilionoid Burkholderia spp. contain duplications of several nod and nif genes. The Burkholderia nifHDKEN and fixABC genes are very closely related to those found in free-living diazotrophs. In contrast, nifA is highly divergent between both groups, but the papilionoid species nifA is more similar to alpha-rhizobia nifA than to other groups. Surprisingly, for all Burkholderia, the fixNOQP and fixGHIS genes required for cbb3 cytochrome oxidase production and assembly are missing. In contrast, symbiotic Cupriavidus strains have fixNOQPGHIS genes, revealing a divergence in the evolution of two distinct electron transport chains required for nitrogen fixation within the beta-rhizobia. PMID- 27269512 TI - The Feasibility of Collecting School Nurse Data. AB - School nurses cite barriers to collecting comprehensive data on the care they provide. This study evaluated the feasibility of collecting school nurse data on selected child health and education outcomes. Outcome variables included school health office visits; health provider, parent, and staff communication; early dismissal; and medications administered. On an average day, the school nurses cared for 43.5 students, administered 14 medications, and averaged of 17 daily communications. Day 1 data collection times averaged 15 min or less. By Day 5, 6.6 min was needed to complete the survey. Data collection was feasible for 76% of those who elected to participate. Feasibility is enhanced by limiting the number of data points and the number of days for data collection using a data collection web interface. Data collection across large numbers of nurses and a wide range of school nurse delivery models is necessary to measure the impact of school nurse presence and interventions on child health and education outcomes. PMID- 27269513 TI - Nurse perspectives on the implementation of routine telemonitoring for high-risk diabetes patients in a primary care setting. AB - : Aims The purpose of this qualitative evaluation was to explore the experience of implementing routine telemonitoring (TM) in real-world primary care settings from the perspective of those delivering the intervention; namely the TM staff, and report on lessons learned that could inform future projects of this type. BACKGROUND: Routine TM for high-risk patients within primary care practices may help improve chronic disease control and reduce complications, including unnecessary hospital admissions. However, little is known about how to integrate routine TM in busy primary care practices. A TM pilot for diabetic patients was attempted in six primary care practices as part of the Beacon Community in Western New York. METHODS: Semi-structured interviews were conducted with representatives of three TM agencies (n=8) participating in the pilot. Interviews were conducted over the phone or in person and lasted ~30 min. Interviews were audio-taped and transcribed. Analysis was conducted using immersion crystallization to identify themes. Findings TM staff revealed several themes related to the experience of delivering TM in real-world primary care: (1) the nurse-patient relationship is central to a successful TM experience, (2) TM is a useful tool for understanding socio-economic context and its impact on patients' health, (3) TM staff anecdotally report important potential impacts on patient health, and (4) integrating TM into primary care practices needs to be planned carefully. CONCLUSIONS: This qualitative study identified challenges and unexpected benefits that might inform future efforts. Communication and integration between the TM agency and the practice, including the designation of a point person within the office to coordinate TM and help address the broader contextual needs of patients, are important considerations for future implementation. The role of the TM nurse in developing trust with patients and uncovering the social and economic context within which patients manage their diabetes was an unexpected benefit. PMID- 27269514 TI - Insight into structural phase transitions from the decoupled anharmonic mode approximation. AB - We develop a formalism (decoupled anharmonic mode approximation, DAMA) that allows calculation of the vibrational free energy using density functional theory even for materials which exhibit negative curvature of the potential energy surface with respect to atomic displacements. We investigate vibrational modes beyond the harmonic approximation and approximate the potential energy surface with the superposition of the accurate potential along each normal mode. We show that the free energy can stabilize crystal structures at finite temperatures which appear dynamically unstable at T = 0. The DAMA formalism is computationally fast because it avoids statistical sampling through molecular dynamics calculations, and is in principle completely ab initio. It is free of statistical uncertainties and independent of model parameters, but can give insight into the mechanism of a structural phase transition. We apply the formalism to the perovskite cryolite, and investigate the temperature-driven phase transition from the P21/n to the Immm space group. We calculate a phase transition temperature between 710 and 950 K, in fair agreement with the experimental value of 885 K. This can be related to the underestimation of the interaction of the vibrational states. We also calculate the main axes of the thermal ellipsoid and can explain the experimentally observed increase of its volume for the fluorine by 200-300% throughout the phase transition. Our calculations suggest the appearance of tunneling states in the high temperature phase. The convergence of the vibrational DOS and of the critical temperature with respect of reciprocal space sampling is investigated using the polarizable ion model. PMID- 27269515 TI - Isolated limb perfusion as a treatment option for rare types of tumours. AB - BACKGROUND: Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. METHODS: Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively. RESULTS: The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%). CONCLUSIONS: These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed. PMID- 27269516 TI - Affinity Induced Surface Functionalization of Liposomes Using Cu-Free Click Chemistry. AB - Functionalization of nanoparticles is a key element for improving specificity of drug delivery systems toward diseased tissue or cells. In the current study we report a highly efficient and chemoselective method for post-functionalization of liposomes with biomacromolecules, which equally well can be used for functionalization of other nanoparticles or solid surfaces. The method exploits a synergistic effect of having both affinity and covalent anchoring tags on the surface of the liposome. This was achieved by synthesizing a peptide linker system that uses Cu-free strain-promoted click chemistry in combination with histidine affinity tags. The investigation of post-functionalization of PEGylated liposomes was performed with a cyclic RGDfE peptide. By exploring both affinity and covalent tags a 98 +/- 2.0% coupling efficiency was achieved, even a diluted system showed a coupling efficiency of 87 +/- 0.2%. The reaction kinetics and overall yield were quantified by HPLC. The results presented here open new possibilities for constructing complex nanostructures and functionalized surfaces. PMID- 27269517 TI - A Metal-Free Protocol for Aminofunctionalization of Olefins Using TsNBr2. AB - N,N-Dibromo-p-toluene sulfonamide (TsNBr2) has been found to be an effective reagent for various aminofunctionalization reactions. This reagent behaves both as an electrophilic bromine source as well as amine to react with olefins under different conditions to yield aminoether, imidazoline, diamine and amino bromine. The reaction proceeds rapidly under mild conditions with high regioselectivity. Olefins react with TsNBr2 in moist THF to form delta-amino ether at room temperature. Treatment of TsNBr2 with olefin in MeCN at room temperature produced imidazoline in high yield. Further modification of the reaction condition resulted in the development of a one-step procedure for the synthesis of N acetyl,N'-tosyl diamine derivatives directly from olefin. When the olefin was treated with 2.4 mol equiv of TsNBr2 in the presence of K2CO3, N,N'-ditosyl diamine derivative was obtained in moderate yield. Instantaneous formation of aminobromine was observed when an olefin was treated with the reagent in dry CH2Cl2 at room temperature. PMID- 27269518 TI - Estimation of conditions evoking fracture in finger bones under pinch loading based on finite element analysis. AB - A finger finite element (FE) model was created from CT images of a Japanese male in order to obtain a shape-biofidelic model. Material properties and articulation characteristics of the model were taken from the literature. To predict bone fracture and realistically represent the fracture pattern under various loading conditions, the ESI-Wilkins-Kamoulakos rupture model in PAM-CRASH (ESI Group S.A., Paris, France) was utilized in this study with parameter values of the rupture model determined by compression testing and simulation of porcine fibula. A finger pinch simulation was then conducted to validate the finger FE model. The force-displacement curve and fracture load from the pinch simulation was compared to the result of finger pinch test using cadavers. Simulation results are coincident with the test result, indicating that the finger FE model can be used in an analysis of finger bone fracture during pinch accident. With this model, several pinch simulations were conducted with different pinching object's stiffness and pinching energy. Conditions for evoking finger bone fracture under pinch loading were then estimated based on these results. This study offers a novel method to predict possible hazards of manufactured goods during the design process, thus finger injury due to pinch loading can be avoided. PMID- 27269519 TI - The Timed Depolarization of Morning and Evening Oscillators Phase Shifts the Circadian Clock of Drosophila. AB - Phase response curves (PRCs) for light or temperature stimuli have been shown to be most valuable in understanding how circadian clocks are entrained to daily environmental cycles. Nowadays, PRC experiments in which clock neurons are manipulated in a temporally restricted manner by thermogenetic or optogenetic tools are also useful to comprehend clock network properties. Here, we temporally depolarized specific clock neurons of Drosophila melanogaster by activating temperature-sensitive dTrpA1 channels to unravel their role in phase shifting the flies' activity rhythm. The depolarization of all clock neurons caused a PRC resembling the flies' light PRC, with strong phase delays in the first half of the subjective night and modest phase advances in its second half. However, the activation of the flies' pigment-dispersing factor (PDF)-positive morning (M) neurons (s-LNvs) only induced phase advances, and these reached into the subjective day, where the light PRC has its dead zone. This indicates that the M neurons are very potent in accelerating the clock, which is in line with previous observations. In contrast, the evening (E) neurons together with the PDF-positive l-LNvs appear to mediate phase delays. Most interestingly, the molecular clock (Period protein cycling) of the depolarized clock neurons was shifted in parallel to the behavior, and this shift was already visible within the first cycle after the temperature pulse. We identified cAMP response element binding protein B (CREB) as a putative link between membrane depolarization and the molecular clock. PMID- 27269520 TI - Ethanol Induced Brain Lipid Changes in Mice Assessed by Mass Spectrometry. AB - Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell membranes, are involved in cell signaling, signal transduction, and energy storage. In this study, we analyzed lipid composition of chronically ethanol exposed mouse brains. Juvenile (JUV) and adult (ADU) mice were placed on a daily limited-access ethanol intake model for 52 days. After euthanasia, brains were harvested, and total lipids were extracted from brain homogenates. Samples were analyzed using high resolution mass spectrometry and processed by multivariate and univariate statistical analysis. Significant lipid changes were observed in different classes including sphingolipids, fatty acids, lysophosphatidylcholines, and other glycerophospholipids. PMID- 27269577 TI - Trimethylsilyl Chloride-Modified Li Anode for Enhanced Performance of Li-S Cells. AB - A facile and effective method to modify Li anode for Li-S cells by exposing Li foils to tetrahydrofuran (THF) solvent, oxygen atmosphere and trimethylsilyl chloride ((CH3)3SiCl) liquid in sequence is proposed. The results of SEM and XPS show the formation of a homogeneous and dense film with a thickness of 84 nm on Li metal surface. AC impedance and polarization test results show the improved interfacial stability. The interfacial resistances as well as polarization potential difference have obviously decreased as compared with that of a pristine Li anode. CV and charge-discharge test results demonstrate that more reversible discharge capacity and higher Coulombic efficiency can be achieved. Specific capacity of 760 mAh g(-1) and an average Coulombic efficiency of 98% are retained after 100 cycles at 0.5C without LiNO3 additive. Additionally, the Li-S cell with a modified Li anode displays a greatly improved rate performance with ~425 mAh g( 1) at 5C, making it more attractive and competitive in the applications of high power supply. PMID- 27269578 TI - Facilitating Goodwill in Workplace Relationships: The Benefits and Challenges. PMID- 27269580 TI - Enhanced Promiscuity of Lipase-Inorganic Nanocrystal Composites in the Epoxidation of Fatty Acids in Organic Media. AB - In the present study, Candida antarctica lipase B (CALB) was encapsulated in inorganic nanocrystal composites with flower-like shapes, retaining 92% of its catalytic activity compared to that of native lipase. Surprisingly, CALB inorganic crystal nanoflowers exhibited promiscuous activity at levels 25- and 4 fold higher than those of native lipase and the commercial immobilized lipase Novozym 435, respectively, as demonstrated by the chemoenzymatic epoxidation of fatty acids conducted in organic media. To the best of our knowledge, we showed for the first time that the promiscuity of enzymes can be significantly improved by enzyme immobilization, suggesting that the enzyme-inorganic nanocrystal composites are a very promising type of immobilized enzyme that can be used to address the challenge of the extremely low efficiency of enzymatic promiscuity. PMID- 27269579 TI - Unmet needs and relationship challenges of head and neck cancer patients and their spouses. AB - In head and neck cancer (HNC), couple-based interventions may be useful for facilitating treatment completion, patient rehabilitation, and improving both partners' quality of life. With the goal of identifying targets for future interventions, we conducted a qualitative study to understand patient and spouse unmet needs and relationship challenges during curative radiotherapy for HNC. Semistructured interviews were conducted with six HNC patients (83% male) and six spouses (83% female) within 6 months of completing treatment. Interviews were audiotaped and transcribed using grounded theory analysis. Patients and spouses identified several unmet needs including better preparation regarding the severity of physical side effects, a clearer timeline for recovery, and strategies for dealing with their own and each other's emotional reactions. Caregiver's unmet needs included balancing competing roles/responsibilities, making time for self-care, and finding effective strategies for encouraging patient's self-care. Eighty-three percent of spouses and all patients reported increased conflict during treatment. Other relationship challenges included changes in intimacy and social/leisure activities. Findings suggest that couple based interventions that emphasize the importance of managing physical and psychological symptoms through the regular practice of self-care routines may be beneficial for both patients and spouses. Likewise, programs that teach spouses ways to effectively motivate and encourage patients' self-care may help minimize conflict and help couples navigate HNC treatment and recovery together as a team. PMID- 27269581 TI - Complementary-addressed site-directed spin labeling of long natural RNAs. AB - Nanoscale distance measurements by pulse dipolar Electron paramagnetic resonance (EPR) spectroscopy allow new insights into the structure and dynamics of complex biopolymers. EPR detection requires site directed spin labeling (SDSL) of biomolecule(s), which remained challenging for long RNAs up-to-date. Here, we demonstrate that novel complementary-addressed SDSL approach allows efficient spin labeling and following structural EPR studies of long RNAs. We succeeded to spin-label Hepatitis C Virus RNA internal ribosome entry site consisting of ~330 nucleotides and having a complicated spatial structure. Application of pulsed double electron-electron resonance provided spin-spin distance distribution, which agrees well with the results of molecular dynamics (MD) calculations. Thus, novel SDSL approach in conjunction with EPR and MD allows structural studies of long natural RNAs with nanometer resolution and can be applied to systems of biological and biomedical significance. PMID- 27269583 TI - Searching the literature for proteins facilitates the identification of biological processes, if advanced methods of analysis are linked: a case study on microgravity-caused changes in cells. AB - BACKGROUND: More than one hundred reports were published about the characterization of cells from malignant and healthy tissues, as well as of endothelial cells and stem cells exposed to microgravity conditions. METHODS: We retrieved publications about microgravity related studies on each type of cells, extracted the proteins mentioned therein and analyzed them aiming to identify biological processes affected by microgravity culture conditions. RESULTS: The analysis revealed 66 different biological processes, 19 of them were always detected when papers about the four types of cells were analyzed. CONCLUSION: Since a response to the removal of gravity is common to the different cell types, some of the 19 biological processes could play a role in cellular adaption to microgravity. Applying computer programs, to extract and analyze proteins and genes mentioned in publications becomes essential for scientists interested to get an overview of the rapidly growing fields of gravitational biology and space medicine. PMID- 27269582 TI - How far from the SNP may the causative genes be? AB - While GWAS identify many disease-associated SNPs, using them to decipher disease mechanisms is hindered by the difficulty in mapping SNPs to genes. Most SNPs are in non-coding regions and it is often hard to identify the genes they implicate. To explore how far the SNP may be from the affected genes we used a pathway-based approach. We found that affected genes are often up to 2 Mbps away from the associated SNP, and are not necessarily the closest genes to the SNP. Existing approaches for mapping SNPs to genes leave many SNPs unmapped to genes and reveal only 86 significant phenotype-pathway associations for all known GWAS hits combined. Using the pathway-based approach we propose here allows mapping of virtually all SNPs to genes and reveals 435 statistically significant phenotype pathway associations. In search for mechanisms that may explain the relationships between SNPs and distant genes, we found that SNPs that are mapped to distant genes have significantly more large insertions/deletions around them than other SNPs, suggesting that these SNPs may sometimes be markers for large insertions/deletions that may affect large genomic regions. PMID- 27269584 TI - Effect of B-Type Natriuretic Peptide Level on Long-Term Outcome in Patients With End-Stage Heart Failure. AB - Previous studies have demonstrated elevated B-type natriuretic peptide (BNP) level indicates a poor outcome in patients with heart failure (HF). However, some patients with end-stage HF presented with low BNP level and the impact of the nearly "normal" BNP level on long-term outcome is not well understood. Our study aimed to evaluate the association of BNP level with long-term outcome in 218 consecutive patients with dilated cardiomyopathy and end-stage HF. Sixty-two patients (28%) presented with admission BNP level <=400 pg/ml. During a median follow-up period of 20 months (4 to 26 months), the all-cause mortality rate in patients with BNP <=400 pg/ml was higher than in patients with BNP >400 pg/ml (76% vs 48%, p <0.001). Patients were then divided into 5 groups according to the BNP level (<=400, 401 to 1,000, 1,001 to 2,000, 2,001 to 3,000, and >3,000 pg/ml), the all-cause mortality were 76%, 41%, 40%, 49%, and 75%, respectively (p <0.001). After multivariate adjustment, both BNP <=400 and >3,000 pg/ml were independently associated with increased risk of all-cause mortality (hazard ratios 1.87, 95% CI 1.02 to 3.42, p = 0.043 and hazard ratio 2.31, 95% CI 1.16 to 4.60, p = 0.018, respectively). In conclusion, our present study demonstrated a "U-like" shape between BNP level and all-cause mortality in end-stage HF, and the seemingly "normal" BNP level might also be a risk factor for poor outcome. Low BNP level may be a reflection of impaired neurohormonal response or altered metabolism of BNP and is associated with increased risk of poor outcome. PMID- 27269585 TI - Gender Differences in In-Hospital Outcomes After Coronary Artery Bypass Grafting. AB - Women historically have a greater risk of operative mortality than men after coronary artery bypass grafting (CABG). There is paucity of contemporary data in gender outcomes of surgical revascularization and understanding modifiable factors that contribute to gender differences are critical for quality improvement and practice change. We, therefore, sought to examine whether the gender gap in CABG outcomes is closing in the contemporary era by conducting a retrospective analysis from the Nationwide Inpatient Sample database from 2003 to 2012. We included all patients who underwent isolated CABG surgery (n = 2,272,998; female n = 623,423 [27.4%]; male n = 1,649,575 [72.6%]). The annual rate of CABG surgeries decreased by 53.7% in men and 57.8% in women over the 10 year study period. Although internal mammary artery use in women was less frequent than in men in 2003 (77.4% vs 81.9%, p <0.001), a significant uptrend closed this gap by 2012 (86.2% vs 87.0%, ptrend 0.003). Overall, unadjusted in hospital mortality was greater in women (3.2% vs 1.8%, p <0.001). Female gender remained an independent predictor of mortality after multivariate adjustment (odds ratio 1.40, 95% CI 1.36 to 1.43, p <0.001) across all age groups. However, in-hospital mortality decreased at a faster rate in women (3.8% to 2.7%, RR 29.1%, ptrend 0.002) than in men (2.2% to 1.6%, RR -25.7%, ptrend <0.001) from 2003 to 2012. In conclusion, CABG rates in the United States are decreasing over time, yet in-hospital mortality continues to improve. Women have worse in hospital outcomes than men; however, the gender gap is slowly closing. PMID- 27269586 TI - Syncope and Dyspnea and Pulmonary Embolism. AB - Failure to recognize ECG features consistent with acute cor pulmonale in a man with new onset syncope and dyspnea resulted in death from undiagnosed pulmonary emboli. PMID- 27269587 TI - Response to "the Use of Mechanical Support Devices in Percutaneous Coronary Interventions: the Controversy?" PMID- 27269588 TI - Removal of nuclease contamination during purification of recombinant prototype foamy virus integrase. AB - Retroviral infection requires integration of the viral genome into the host genome. Recombinant integrase proteins may be purified following bacterial expression. A bulk biochemical assay of integrase function relies on the conversion of supercoiled plasmids to linear or relaxed circles. Single molecule molecular tweezer assays of integrase also evaluate the conversion of supercoiled DNA to nicked and broken species. A bacterial nuclease that co-purifies with retroviral integrase may affect the quantitation of integration activity in bulk or single molecule assays. During purification of retroviral integrase from bacteria, fractions may be screened for contaminating nuclease activity. In order to efficiently separate the nuclease from integrase, the binding affinities of each protein must differ. We find that a co-purifying nuclease may be efficiently separated from integrase based on heparin affinity, but not ionic affinity. PMID- 27269589 TI - Model-based metabolic engineering enables high yield itaconic acid production by Escherichia coli. AB - Itaconic acid is a high potential platform chemical which is currently industrially produced by Aspergillus terreus. Heterologous production of itaconic acid with Escherichia coli could help to overcome limitations of A. terreus regarding slow growth and high sensitivity to oxygen supply. However, the performance achieved so far with E. coli strains is still low. We introduced a plasmid (pCadCS) carrying genes for itaconic acid production into E. coli and applied a model-based approach to construct a high yield production strain. Based on the concept of minimal cut sets, we identified intervention strategies that guarantee high itaconic acid yield while still allowing growth. One cut set was selected and the corresponding genes were iteratively knocked-out. As a conceptual novelty, we pursued an adaptive approach allowing changes in the model and initially calculated intervention strategy if a genetic modification induces changes in byproduct formation. Using this approach, we iteratively implemented five interventions leading to high yield itaconic acid production in minimal medium with glucose as substrate supplemented with small amounts of glutamic acid. The derived E. coli strain (ita23: MG1655 ?aceA ?sucCD ?pykA ?pykF ?pta ?Picd::cam_BBa_J23115 pCadCS) synthesized 2.27g/l itaconic acid with an excellent yield of 0.77mol/(mol glucose). In a fed-batch cultivation, this strain produced 32g/l itaconic acid with an overall yield of 0.68mol/(mol glucose) and a peak productivity of 0.45g/l/h. These values are by far the highest that have ever been achieved for heterologous itaconic acid production and indicate that realistic applications come into reach. PMID- 27269590 TI - Free Carriers versus Excitons in CH3NH3PbI3 Perovskite Thin Films at Low Temperatures: Charge Transfer from the Orthorhombic Phase to the Tetragonal Phase. AB - We have investigated the dynamic optical properties of CH3NH3PbI3 (MAPbI3) perovskite thin films at low temperatures using time-resolved photoluminescence, optical transient absorption (TA), and THz TA spectroscopy. Optical spectroscopic results indicate that the high-temperature tetragonal phase still remains in the MAPbI3 thin films at low temperatures in addition to the major orthorhombic phase. The fast charge transfer from the orthorhombic phase to the tetragonal phase is likely to suppress the formation of excitons in the orthorhombic phase. Consequently, the near-band-edge optical responses of the photocarriers in both the tetragonal and orthorhombic phases of the MAPbI3 thin films are more accurately described by a free-carrier model, rather than an excitonic model even at low temperatures. PMID- 27269591 TI - Pregnant women's preference for cesarean section and subsequent mode of birth - a six-country cohort study. AB - INTRODUCTION: The rate of cesarean section (CS) for non-medical reasons has risen and it is a concern for health care. Women's preferences may vary across countries for psychosocial or obstetric reasons. METHODS: A prospective cohort study of 6549 women in routine antenatal care giving birth in Belgium, Iceland, Denmark, Estonia, Norway or Sweden. Preference for mode of birth was self reported in mid-pregnancy. Birth outcome data were collected from hospital records. RESULTS: A CS was preferred by 3.5% of primiparous women and 8.7% of the multiparous women. Preference for CS was associated with severe fear of childbirth (FOC), with a negative birth experience in multiparous women and with depressive symptoms in the primiparous. Women were somewhat more prone to prefer a cesarean in Iceland, odd ratio (OR) 1.70 (1.02-2.83), adjusted for age, education, depression, FOC, history of abuse, previous cesarean and negative birth experience. Out of the 404 women who preferred CS during pregnancy, 286 (70.8%) delivered by CS, mostly for a medical indication. A total of 9% of the cesareans in the cohort had a non-medical indication only. CONCLUSIONS: Women's preference for CS often seems to be due to health concerns. Both medical and psychological factors need to be addressed in antenatal counseling. Obstetricians need to convey accurately to women the risks and benefits of CS in her specific case. Maternity professionals should identify and explore psychosocial reasons for women's preferences. PMID- 27269594 TI - Is the UK spending more than we thought on healthcare (and much less on social care)? PMID- 27269595 TI - Vision in our three-dimensional world. AB - Many aspects of our perceptual experience are dominated by the fact that our two eyes point forward. Whilst the location of our eyes leaves the environment behind our head inaccessible to vision, co-ordinated use of our two eyes gives us direct access to the three-dimensional structure of the scene in front of us, through the mechanism of stereoscopic vision. Scientific understanding of the different brain regions involved in stereoscopic vision and three-dimensional spatial cognition is changing rapidly, with consequent influences on fields as diverse as clinical practice in ophthalmology and the technology of virtual reality devices.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269596 TI - Stereoscopic depth constancy. AB - Depth constancy is the ability to perceive a fixed depth interval in the world as constant despite changes in viewing distance and the spatial scale of depth variation. It is well known that the spatial frequency of depth variation has a large effect on threshold. In the first experiment, we determined that the visual system compensates for this differential sensitivity when the change in disparity is suprathreshold, thereby attaining constancy similar to contrast constancy in the luminance domain. In a second experiment, we examined the ability to perceive constant depth when the spatial frequency and viewing distance both changed. To attain constancy in this situation, the visual system has to estimate distance. We investigated this ability when vergence, accommodation and vertical disparity are all presented accurately and therefore provided veridical information about viewing distance. We found that constancy is nearly complete across changes in viewing distance. Depth constancy is most complete when the scale of the depth relief is constant in the world rather than when it is constant in angular units at the retina. These results bear on the efficacy of algorithms for creating stereo content.This article is part of the themed issue 'Vision in our three dimensional world'. PMID- 27269597 TI - Effects of cortical damage on binocular depth perception. AB - Stereoscopic depth perception requires considerable neural computation, including the initial correspondence of the two retinal images, comparison across the local regions of the visual field and integration with other cues to depth. The most common cause for loss of stereoscopic vision is amblyopia, in which one eye has failed to form an adequate input to the visual cortex, usually due to strabismus (deviating eye) or anisometropia. However, the significant cortical processing required to produce the percept of depth means that, even when the retinal input is intact from both eyes, brain damage or dysfunction can interfere with stereoscopic vision. In this review, I examine the evidence for impairment of binocular vision and depth perception that can result from insults to the brain, including both discrete damage, temporal lobectomy and more systemic diseases such as posterior cortical atrophy.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269598 TI - Disparity processing in primary visual cortex. AB - The first step in binocular stereopsis is to match features on the left retina with the correct features on the right retina, discarding 'false' matches. The physiological processing of these signals starts in the primary visual cortex, where the binocular energy model has been a powerful framework for understanding the underlying computation. For this reason, it is often used when thinking about how binocular matching might be performed beyond striate cortex. But this step depends critically on the accuracy of the model, and real V1 neurons show several properties that suggest they may be less sensitive to false matches than the energy model predicts. Several recent studies provide empirical support for an extended version of the energy model, in which the same principles are used, but the responses of single neurons are described as the sum of several subunits, each of which follows the principles of the energy model. These studies have significantly improved our understanding of the role played by striate cortex in the stereo correspondence problem.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269599 TI - The neural basis of depth perception from motion parallax. AB - In addition to depth cues afforded by binocular vision, the brain processes relative motion signals to perceive depth. When an observer translates relative to their visual environment, the relative motion of objects at different distances (motion parallax) provides a powerful cue to three-dimensional scene structure. Although perception of depth based on motion parallax has been studied extensively in humans, relatively little is known regarding the neural basis of this visual capability. We review recent advances in elucidating the neural mechanisms for representing depth-sign (near versus far) from motion parallax. We examine a potential neural substrate in the middle temporal visual area for depth perception based on motion parallax, and we explore the nature of the signals that provide critical inputs for disambiguating depth-sign.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269600 TI - Weighted parallel contributions of binocular correlation and match signals to conscious perception of depth. AB - Binocular disparity is detected in the primary visual cortex by a process similar to calculation of local cross-correlation between left and right retinal images. As a consequence, correlation-based neural signals convey information about false disparities as well as the true disparity. The false responses in the initial disparity detectors are eliminated at later stages in order to encode only disparities of the features correctly matched between the two eyes. For a simple stimulus configuration, a feed-forward nonlinear process can transform the correlation signal into the match signal. For human observers, depth judgement is determined by a weighted sum of the correlation and match signals rather than depending solely on the latter. The relative weight changes with spatial and temporal parameters of the stimuli, allowing adaptive recruitment of the two computations under different visual circumstances. A full transformation from correlation-based to match-based representation occurs at the neuronal population level in cortical area V4 and manifests in single-neuron responses of inferior temporal and posterior parietal cortices. Neurons in area V5/MT represent disparity in a manner intermediate between the correlation and match signals. We propose that the correlation and match signals in these areas contribute to depth perception in a weighted, parallel manner.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269601 TI - Depth perception in disparity-defined objects: finding the balance between averaging and segregation. AB - Deciding what constitutes an object, and what background, is an essential task for the visual system. This presents a conundrum: averaging over the visual scene is required to obtain a precise signal for object segregation, but segregation is required to define the region over which averaging should take place. Depth, obtained via binocular disparity (the differences between two eyes' views), could help with segregation by enabling identification of object and background via differences in depth. Here, we explore depth perception in disparity-defined objects. We show that a simple object segregation rule, followed by averaging over that segregated area, can account for depth estimation errors. To do this, we compared objects with smoothly varying depth edges to those with sharp depth edges, and found that perceived peak depth was reduced for the former. A computational model used a rule based on object shape to segregate and average over a central portion of the object, and was able to emulate the reduction in perceived depth. We also demonstrated that the segregated area is not predefined but is dependent on the object shape. We discuss how this segregation strategy could be employed by animals seeking to deter binocular predators.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269603 TI - Defining the V5/MT neuronal pool for perceptual decisions in a visual stereo motion task. AB - In the primate visual cortex, neurons signal differences in the appearance of objects with high precision. However, not all activated neurons contribute directly to perception. We defined the perceptual pool in extrastriate visual area V5/MT for a stereo-motion task, based on trial-by-trial co-variation between perceptual decisions and neuronal firing (choice probability (CP)). Macaque monkeys were trained to discriminate the direction of rotation of a cylinder, using the binocular depth between the moving dots that form its front and rear surfaces. We manipulated the activity of single neurons trial-to-trial by introducing task-irrelevant stimulus changes: dot motion in cylinders was aligned with neuronal preference on only half the trials, so that neurons were strongly activated with high firing rates on some trials and considerably less activated on others. We show that single neurons maintain high neurometric sensitivity for binocular depth in the face of substantial changes in firing rate. CP was correlated with neurometric sensitivity, not level of activation. In contrast, for individual neurons, the correlation between perceptual choice and neuronal activity may be fundamentally different when responding to different stimulus versions. Therefore, neuronal pools supporting sensory discrimination must be structured flexibly and independently for each stimulus configuration to be discriminated.This article is part of the themed issue 'Vision in our three dimensional world'. PMID- 27269602 TI - Binocular depth processing in the ventral visual pathway. AB - One of the most powerful forms of depth perception capitalizes on the small relative displacements, or binocular disparities, in the images projected onto each eye. The brain employs these disparities to facilitate various computations, including sensori-motor transformations (reaching, grasping), scene segmentation and object recognition. In accordance with these different functions, disparity activates a large number of regions in the brain of both humans and monkeys. Here, we review how disparity processing evolves along different regions of the ventral visual pathway of macaques, emphasizing research based on both correlational and causal techniques. We will discuss the progression in the ventral pathway from a basic absolute disparity representation to a more complex three-dimensional shape code. We will show that, in the course of this evolution, the underlying neuronal activity becomes progressively more bound to the global perceptual experience. We argue that these observations most probably extend beyond disparity processing per se, and pertain to object processing in the ventral pathway in general. We conclude by posing some important unresolved questions whose answers may significantly advance the field, and broaden its scope.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269604 TI - Neural architectures for stereo vision. AB - Stereoscopic vision delivers a sense of depth based on binocular information but additionally acts as a mechanism for achieving correspondence between patterns arriving at the left and right eyes. We analyse quantitatively the cortical architecture for stereoscopic vision in two areas of macaque visual cortex. For primary visual cortex V1, the result is consistent with a module that is isotropic in cortical space with a diameter of at least 3 mm in surface extent. This implies that the module for stereo is larger than the repeat distance between ocular dominance columns in V1. By contrast, in the extrastriate cortical area V5/MT, which has a specialized architecture for stereo depth, the module for representation of stereo is about 1 mm in surface extent, so the representation of stereo in V5/MT is more compressed than V1 in terms of neural wiring of the neocortex. The surface extent estimated for stereo in V5/MT is consistent with measurements of its specialized domains for binocular disparity. Within V1, we suggest that long-range horizontal, anatomical connections form functional modules that serve both binocular and monocular pattern recognition: this common function may explain the distortion and disruption of monocular pattern vision observed in amblyopia.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269605 TI - Small or far away? Size and distance perception in the praying mantis. AB - Stereo or '3D' vision is an important but costly process seen in several evolutionarily distinct lineages including primates, birds and insects. Many selective advantages could have led to the evolution of stereo vision, including range finding, camouflage breaking and estimation of object size. In this paper, we investigate the possibility that stereo vision enables praying mantises to estimate the size of prey by using a combination of disparity cues and angular size cues. We used a recently developed insect 3D cinema paradigm to present mantises with virtual prey having differing disparity and angular size cues. We predicted that if they were able to use these cues to gauge the absolute size of objects, we should see evidence for size constancy where they would strike preferentially at prey of a particular physical size, across a range of simulated distances. We found that mantises struck most often when disparity cues implied a prey distance of 2.5 cm; increasing the implied distance caused a significant reduction in the number of strikes. We, however, found no evidence for size constancy. There was a significant interaction effect of the simulated distance and angular size on the number of strikes made by the mantis but this was not in the direction predicted by size constancy. This indicates that mantises do not use their stereo vision to estimate object size. We conclude that other selective advantages, not size constancy, have driven the evolution of stereo vision in the praying mantis.This article is part of the themed issue 'Vision in our three dimensional world'. PMID- 27269606 TI - Lesions to right posterior parietal cortex impair visual depth perception from disparity but not motion cues. AB - The posterior parietal cortex (PPC) is understood to be active when observers perceive three-dimensional (3D) structure. However, it is not clear how central this activity is in the construction of 3D spatial representations. Here, we examine whether PPC is essential for two aspects of visual depth perception by testing patients with lesions affecting this region. First, we measured subjects' ability to discriminate depth structure in various 3D surfaces and objects using binocular disparity. Patients with lesions to right PPC (N = 3) exhibited marked perceptual deficits on these tasks, whereas those with left hemisphere lesions (N = 2) were able to reliably discriminate depth as accurately as control subjects. Second, we presented an ambiguous 3D stimulus defined by structure from motion to determine whether PPC lesions influence the rate of bistable perceptual alternations. Patients' percept durations for the 3D stimulus were generally within a normal range, although the two patients with bilateral PPC lesions showed the fastest perceptual alternation rates in our sample. Intermittent stimulus presentation reduced the reversal rate similarly across subjects. Together, the results suggest that PPC plays a causal role in both inferring and maintaining the perception of 3D structure with stereopsis supported primarily by the right hemisphere, but do not lend support to the view that PPC is a critical contributor to bistable perceptual alternations.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269607 TI - Recovering stereo vision by squashing virtual bugs in a virtual reality environment. AB - Stereopsis is the rich impression of three-dimensionality, based on binocular disparity-the differences between the two retinal images of the same world. However, a substantial proportion of the population is stereo-deficient, and relies mostly on monocular cues to judge the relative depth or distance of objects in the environment. Here we trained adults who were stereo blind or stereo-deficient owing to strabismus and/or amblyopia in a natural visuomotor task-a 'bug squashing' game-in a virtual reality environment. The subjects' task was to squash a virtual dichoptic bug on a slanted surface, by hitting it with a physical cylinder they held in their hand. The perceived surface slant was determined by monocular texture and stereoscopic cues, with these cues being either consistent or in conflict, allowing us to track the relative weighting of monocular versus stereoscopic cues as training in the task progressed. Following training most participants showed greater reliance on stereoscopic cues, reduced suppression and improved stereoacuity. Importantly, the training-induced changes in relative stereo weights were significant predictors of the improvements in stereoacuity. We conclude that some adults deprived of normal binocular vision and insensitive to the disparity information can, with appropriate experience, recover access to more reliable stereoscopic information.This article is part of the themed issue 'Vision in our three-dimensional world'. PMID- 27269608 TI - A moving observer in a three-dimensional world. AB - For many tasks such as retrieving a previously viewed object, an observer must form a representation of the world at one location and use it at another. A world based three-dimensional reconstruction of the scene built up from visual information would fulfil this requirement, something computer vision now achieves with great speed and accuracy. However, I argue that it is neither easy nor necessary for the brain to do this. I discuss biologically plausible alternatives, including the possibility of avoiding three-dimensional coordinate frames such as ego-centric and world-based representations. For example, the distance, slant and local shape of surfaces dictate the propensity of visual features to move in the image with respect to one another as the observer's perspective changes (through movement or binocular viewing). Such propensities can be stored without the need for three-dimensional reference frames. The problem of representing a stable scene in the face of continual head and eye movements is an appropriate starting place for understanding the goal of three dimensional vision, more so, I argue, than the case of a static binocular observer.This article is part of the themed issue 'Vision in our three dimensional world'. PMID- 27269609 TI - Effects of generalized pooling on binocular disparity selectivity of neurons in the early visual cortex. AB - The key problem of stereoscopic vision is traditionally defined as accurately finding the positional shifts of corresponding object features between left and right images. Here, we demonstrate that the problem must be considered in a four dimensional parameter space; with respect not only to shifts in space (X, Y), but also spatial frequency (SF) and orientation (OR). The proposed model sums outputs of binocular energy units linearly over the multi-dimensional V1 parameter space (X, Y, SF, OR). Theoretical analyses and physiological experiments show that many binocular neurons achieve sharp binocular tuning properties by pooling the output of multiple neurons with relatively broad tuning. Pooling in the space domain sharpens disparity-selective responses in the SF domain so that the responses to combinations of unmatched left-right SFs are attenuated. Conversely, pooling in the SF domain sharpens disparity selectivity in the space domain, reducing the possibility of false matches. Analogous effects are observed for the OR domain in that the spatial pooling sharpens the binocular tuning in the OR domain. Such neurons become selective to relative OR disparity. Therefore, pooling allows the visual system to refine binocular information into a form more desirable for stereopsis.This article is part of the themed issue 'Vision in our three dimensional world'. PMID- 27269610 TI - T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS. AB - BACKGROUND AND OBJECTIVES: Rituximab is used with variable success in difficult FSGS. Because B cell depletion significantly affects T cell function, we characterized T cell subsets in patients with FSGS to determine if an immunologic signature predictive of favorable response to rituximab could be identified. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-two consecutive patients with FSGS (median age =14.4 years old; range =6.2-25.0 years old) and age of onset of nephrotic syndrome 1-18 years old receiving rituximab for clinical indications between October of 2009 and February of 2014 were studied. Indications for rituximab were lack of sustained remission despite calcineurin inhibitors (CNIs) and mycophenolate in steroid-resistant patients and lack of steroid-sparing effect with cyclophosphamide and CNI or CNI toxicity in steroid dependent patients. Exclusion criteria were infantile onset, known genetic mutations, and secondary causes. Rituximab (375 mg/m(2)) was given fortnightly up to a maximum of four doses. Immunologic subset monitoring was performed at baseline and regular intervals until relapse. Median follow-up duration postrituximab was 26.7 months (range =6.5-66.5 months). Baseline immunologic subsets were examined for association with rituximab response defined as resolution of proteinuria with discontinuation of prednisolone and CNI 3 months postrituximab. RESULTS: Twelve patients (54.5%) responded to rituximab. Mitogen stimulated CD154(+)CD4(+)CD3(+) subset before rituximab was significantly lower in FSGS responders compared with nonresponders (54.9%+/-28.1% versus 78.9%+/ 16.4%; P=0.03). IFN-gamma(+)CD3(+) and IL-2(+)CD3(+) were similarly decreased in responders compared with nonresponders (0.6%+/-0.8% versus 7.5%+/-6.1%; P=0.003 and 0.2%+/-0.5% versus 4.0%+/-4.7%; P<0.01, respectively). Recovery of all three activation subsets occurred 6 months postrituximab treatment (CD154(+)CD4(+)CD3(+), 74.8%+/-17.2%; IFN-gamma(+)CD3(+), 7.1%+/-7.7%; and IL 2(+)CD3(+), 7.9%+/-10.9%; P<0.01). Receiver-operating characteristic analysis using optimal cutoff values showed that activated CD154(+)CD4(+)CD3(+) <83.3% (area under the curve [AUC], 0.81; 95% confidence interval [95% CI], 0.61 to 1.00), IFN-gamma(+)CD3(+)<2.5% (AUC, 0.90; 95% CI, 0.75 to 1.00), and IL 2(+)CD3(+)<0.3% (AUC, 0.78; 95% CI, 0.57 to 0.98) were good predictors of rituximab response. CONCLUSIONS: We have identified prognostic markers that define a subset of patients with FSGS bearing an immunologic signature representing hyporesponsiveness to T cell stimulation and therefore, who respond better to rituximab. PMID- 27269611 TI - Geovariation in Fracture Risk among Patients Receiving Hemodialysis. AB - BACKGROUND AND OBJECTIVES: Fractures are a major source of morbidity and mortality in patients receiving dialysis. We sought to determine whether rates of fractures and tendon ruptures vary geographically. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the US Renal Data System were used to create four yearly cohorts, 2007-2010, including all eligible prevalent patients on hemodialysis in the United States on January 1 of each year. A secondary analysis comprising patients in a large dialysis organization conducted over the same period permitted inclusion of patient-level markers of mineral metabolism. Patients were grouped into 10 regions designated by the Centers for Medicare and Medicaid Services and divided by latitude into one of three bands: south, <35 degrees ; middle, 35 degrees to <40 degrees ; and north, >=40 degrees . Poisson regression was used to calculate unadjusted and adjusted region-level rate ratios for events. RESULTS: Overall, 327,615 patients on hemodialysis were included. Mean (SD) age was 61.8 (15.0) years old, 52.7% were white, and 55.0% were men. During 716,962 person-years of follow-up, 44,014 fractures and tendon ruptures occurred, the latter being only 0.3% of overall events. Event rates ranged from 5.36 to 7.83 per 100 person-years, a 1.5-fold rate difference across regions. Unadjusted region-level rate ratios varied from 0.83 (95% confidence interval, 0.81 to 0.85) to 1.20 (95% confidence interval, 1.18 to 1.23), a 1.45-fold rate difference. After adjustment for a wide range of case mix variables, a 1.33-fold variation in rates remained. Rates were higher in north and middle bands than the south (north rate ratio, 1.18; 95% confidence interval, 1.13 to 1.23; middle rate ratio, 1.13; 95% confidence interval, 1.10 to 1.17). Latitude explained 11% of variation, independent of region. A complementary analysis of 87,013 patients from a large dialysis organization further adjusted for circulating mineral metabolic parameters and protein energy wasting yielded similar results. CONCLUSIONS: Rates of fractures vary geographically in the United States dialysis population, even after adjustment for known patient characteristics. Latitude seems to contribute to this phenomenon, but additional analyses exploring whether other factors might influence variation are warranted. PMID- 27269613 TI - Assessment of the quality of cervical mucus among users of the levonorgestrel releasing intrauterine system at different times of use. AB - BACKGROUND AND OBJECTIVES: The quality of cervical mucus (CM) among the levonorgestrel-releasing intrauterine system (LNG-IUS) users is controversial. The objectives were to assess CM compared to the levels of oestradiol (E2) and the frequency of cycles with luteal activity among users of the LNG-IUS. MATERIALS AND METHODS: In total, 224 LNG-IUS users for between two months and five years were recruited at a Brazilian family planning clinic. For the cross sectional part of the study, we enrolled 175 LNG-IUS users at 2, 6 12, 24, 36, 48, and 60 months after insertion (25 women in each group), and we performed one evaluation. For the prospective part of the study, we enrolled 49 LNG-IUS users at the same lengths of use after insertion (7 women in each group), and we evaluated these women once a week for five consecutive weeks. . RESULTS: Mean (+/ SEM) CM scores of all evaluations among women with single and weekly evaluations were between 3.3 +/- 0.9 and 8.5 +/- 0.3, respectively independently of the length of use of the LNG-IUS. Mean E2 values ranged from 45.5 +/- 6.8 to 472.5 +/ 34.7 pg/ml and the maximum ovarian follicle diameter on the days of evaluation varied from 14.0 +/- 1.3 to 31.2 +/- 0.4 mm. CONCLUSIONS: The mean CM score of all evaluations, independent of the length of use of the LNG-IUS and normal levels of serum E2, was below 10 was according to the WHO is inadequate for sperm penetration. PMID- 27269614 TI - The spatio-temporal partitioning of sperm by males of the prospermatogenic parasitoid Nasonia vitripennis is in line with its gregarious lifestyle. AB - Male fitness depends on the number of lifetime progeny of their mates and could be constrained by the chance of finding a mate, lifespan and temporal patterns of sperm production and allocation. Here, we used the parasitic wasp Nasonia vitripennis with a two-week lifespan and a gregarious lifestyle, to analyze how the reproductive system is organized to allocate spermatozoa over consecutive matings. Results show that spermatogenesis is synchronized and completed one day before emergence so that males emerge with a full sperm complement. We also found a regulation of spermatozoa transfer between testis and seminal vesicles that allows males to partition small ejaculates over multiple matings. Overall, this study shows that for N. vitripennis, male fertilization potential is determined (1) at the pupal stage, when spermatogenesis takes place to generate a complete life-long stock, (2) on emergence, when transport of spermatozoa from testes to seminal vesicles is initiated and (3) in adulthood, during which spermatozoa are partitioned over successive copulations. Such life history-traits are consistent with the gregarious lifestyle of N. vitripennis. PMID- 27269612 TI - Achieving Procedural Competence during Nephrology Fellowship Training: Current Requirements and Educational Research. AB - Concerns have previously been raised as to whether training programs are ensuring that nephrology fellows achieve competence in the procedural skills required for independent practice. We sought to review the current requirements for procedural training as well as educational research pertaining to achieving competence in the core nephrology procedures of nontunneled (temporary) hemodialysis catheter insertion and percutaneous kidney biopsy. At this time, there is no universal approach to procedural training and assessment during nephrology fellowship. Nonetheless, simulation-based mastery learning programs have been shown to be effective in improving fellows' skills in nontunneled (temporary) hemodialysis catheter insertion and should be provided by all nephrology training programs. For percutaneous kidney biopsy, the development and evaluation of inexpensive simulators are a promising starting point for future study. Current practice with respect to procedural training during nephrology fellowship remains imperfect; however, the ongoing shift toward competency-based evaluation provides opportunities to refocus on improvement. PMID- 27269631 TI - Biofabrication of 3D Alginate-Based Hydrogel for Cancer Research: Comparison of Cell Spreading, Viability, and Adhesion Characteristics of Colorectal HCT116 Tumor Cells. AB - Hydrogels are an important class of biomaterials as they could mimic the extracellular matrix (ECM). Among the naturally occurring biopolymers, alginate and gelatin are extensively used for many biomedical applications. For developing biofabrication constructs as three-dimensional (3D) cell culture models, realistic imaging of cell spreading and proliferation inside the hydrogels represents a major challenge. Therefore, we aimed to establish a system that can mimic the structural architecture, composition, and biological functions of the ECM for cancer research approaches. For this, we compared the cell behavior of human colon cancer HCT116 cells in two biofabricated hydrogels as follows: pure alginate and cross-linked alginate-gelatin (ADA-GEL) matrixes. Our data indicate that cells from the ADA-GEL matrix showed highest proliferation and cellular networks through the material. Analyzing the mRNA expression of several integrins of cells cultured inside of the matrix, we showed that mRNA expression of integrin subunits differed based on the cell focal adhesion characteristics. Furthermore, we showed that recultured ADA-GEL immobilized cells do not differ from parental HCT116 cells regarding migration and proliferation capabilities. Comparing adhesion and other phenotypic characteristics of HCT116 tumor cells, we suggest that ADA-GEL hydrogel is a more suitable 3D system than pure alginate and seems to optimally mimic the physiological behavior of the tumor microenvironment. For the first time, we present a functional 3D hydrogel construct for colon cancer cells, which are supporting their physiological cell attachment, spreading, and viability. We strongly believe that it will be applicable as a suitable in vitro 3D tumor model to study different aspects of tumor cell behavior. PMID- 27269632 TI - The Sandwich Generation Diner: Development of a Web-Based Health Intervention for Intergenerational Caregivers. AB - BACKGROUND: Women are disproportionately likely to assist aging family members; approximately 53 million in the United States are involved with the health care of aging parents, in-laws, or other relatives. The busy schedules of "sandwich generation" women who care for older relatives require accessible and flexible health education, including Web-based approaches. OBJECTIVE: This paper describes the development and implementation of a Web-based health education intervention, The Sandwich Generation Diner, as a tool for intergenerational caregivers of older adults with physical and cognitive impairments. METHODS: We used Bartholomew's Intervention Mapping (IM) process to develop our theory-based health education program. Bandura's (1997) self-efficacy theory provided the overarching theoretical model. RESULTS: The Sandwich Generation Diner website features four modules that address specific health care concerns. Our research involves randomly assigning caregiver participants to one of two experimental conditions that are identical in the type of information provided, but vary significantly in the presentation. In addition to structured Web-based assessments, specific website usage data are recorded. CONCLUSIONS: The Sandwich Generation Diner was developed to address some of the informational and self efficacy needs of intergenerational female caregivers. The next step is to demonstrate that this intervention is: (1) attractive and effective with families assisting older adults, and (2) feasible to embed within routine home health services for older adults. PMID- 27269633 TI - The Cumbria Rural Health Forum: initiating change and moving forward with technology. AB - INTRODUCTION: The Cumbria Rural Health Forum was formed by a number of public, private and voluntary sector organisations to collaboratively work on rural health and social care in the county of Cumbria, England. The aim of the forum is to improve health and social care delivery for rural communities, and share practical ideas and evidence-based best practice that can be implemented in Cumbria. The forum currently consists of approximately 50 organisations interested in and responsible for delivery of health and social care in Cumbria. An exploration of digital technologies for health and care was recognised as an initial priority. This article describes a hands-on approach undertaken within the forum, including its current progress and development. METHODS: The forum used a modified Delphi technique to facilitate its work on discussing ideas and reaching consensus to formulate the Cumbria Strategy for Digital Technologies in Health and Social Care. The group communication process took place over meetings and workshops held at various locations in the county. RESULTS: A roadmap for the implementation of digital technologies into health and social care was developed. The roadmap recommends the following: (i) to improve the health outcomes for targeted groups, within a unit, department or care pathway; (ii) to explain, clarify, share good (and bad) practice, assess impact and value through information sharing through conferences and events, influencing and advocacy for Cumbria; and (iii) to develop a digital-health-ready workforce where health and social care professionals can be supported to use digital technologies, and enhance recruitment and retention of staff. CONCLUSIONS: The forum experienced issues consistent with those in other Delphi studies, such as the repetition of ideas. Attendance was variable due to the unavailability of key people at times. Although the forum facilitated collective effort to address rural health issues, its power is limited to influencing and supporting implementation of change. Within the implementation phase, the forum has engaged in advising and facilitating policy change at all levels. Thus, the forum has become a voice to influence change towards the advancement of health and social care through digital technologies. The forum continues to serve as a think tank and influencer for change in rural health and social care issues in Cumbria. The forum has increased awareness of digital health and social care solutions, mapped best practice and developed a digital strategy for health and social care in Cumbria. PMID- 27269635 TI - Analyzing the Evolution of Membrane Fouling via a Novel Method Based on 3D Optical Coherence Tomography Imaging. AB - The development of novel tools for studying the fouling behavior during membrane processes is critical. This work explored optical coherence tomography (OCT) to quantitatively interpret the formation of a cake layer during a membrane process; the quantitative analysis was based on a novel image processing method that was able to precisely resolve the 3D structure of the cake layer on a micrometer scale. Fouling experiments were carried out with foulants having different physicochemical characteristics (silica nanoparticles and bentonite particles). The cake layers formed at a series of times were digitalized using the OCT-based characterization. The specific deposit (cake volume/membrane surface area) and surface coverage were evaluated as a function of time, which for the first time provided direct experimental evidence for the transition of various fouling mechanisms. Axial stripes were observed in the grayscale plots showing the deposit distribution in the scanned area; this interesting observation was in agreement with the instability analysis that correlated the polarized particle groups with the small disturbances in the boundary layer. This work confirms that the OCT-based characterization is able to provide deep insights into membrane fouling processes and offers a powerful tool for exploring membrane processes with enhanced performance. PMID- 27269634 TI - Simulated Microgravity Disrupts Cytoskeleton Organization and Increases Apoptosis of Rat Neural Crest Stem Cells Via Upregulating CXCR4 Expression and RhoA-ROCK1 p38 MAPK-p53 Signaling. AB - Neural crest stem cells (NCSCs) are a population of multipotent stem cells that are distributed broadly in many tissues and organs and are capable of differentiating into a variety of cell types that are dispersed throughout three germ layers. We are interested in studying the effects of simulated microgravity on the survival and self-renewal of NCSCs. NCSCs extracted from the hair follicle bulge region of the rat whisker pad were cultured in vitro, respectively, in a 2D adherent environment and a 3D suspension environment using the rotatory cell culture system (RCCS) to simulate microgravity. We found that rat NCSCs (rNCSCs) cultured in the RCCS for 24 h showed disrupted organization of filamentous actin, increased globular actin level, formation of plasma membrane blebbing and neurite like artifact, as well as decreased levels of cortactin and vimentin. Interestingly, ~70% of RCCS-cultured rNCSCs co-expressed cleaved (active) caspase 3 and neuronal markers microtubule-associated protein 2 (MAP2) and Tuj1 instead of NCSC markers, suggesting stress-induced formation of neurite-like artifact in rNCSCs. In addition, rNCSCs showed increased C-X-C chemokine receptor 4 (CXCR4) expression, RhoA GTPase activation, Rho-associated kinase 1 (ROCK1) and p38 mitogen-activated protein kinase (MAPK) phosphorylation, and p53 expression in the nucleus. Incubation of rNCSCs with the Galpha protein inhibitor pertussis toxin or CXCR4 siRNA during RCCS-culturing prevented cytoskeleton disorganization and plasma membrane blebbing, and it suppressed apoptosis of rNCSCs. Taken together, we demonstrate for the first time that simulated microgravity disrupts cytoskeleton organization and increases apoptosis of rNCSCs via upregulating CXCR4 expression and the RhoA-ROCK1-p38 MAPK-p53 signaling pathway. PMID- 27269636 TI - Efflux transporter variants as predictors of drug toxicity in lung cancer patients: systematic review and meta-analysis. AB - Chemotherapeutic drugs are underutilized in lung cancer management due in part to serious adverse drug reactions (ADRs). AIM: With studies revealing an association between interindividual patient ADR variation and efflux transporter variants, we carried out a meta-analysis and systemic review, in order to highlight current knowledge regarding the strength of association between efflux transporter SNPs variants and chemotherapeutic-drug induced ADRs. MATERIALS & METHODS: Papers were sourced from MEDLINE, Cochrane Library, CINHL, EMBASE, Web of Knowledge, Scopus. The Cochrane Collaboration Risk of Bias Tool v13 was used to evaluate six types of bias domains for each of the publications reviewed. RESULTS: Twenty-five publications comprising three randomised control trials, two retrospective case controls and 20 clinical observation studies, totalling 3578 patients, were deemed eligible for review. Of the known efflux drug transporters, we report findings on the ABC members ABCB1, ABCC1, ABCC2, ABCG2, ABCA1, ABCC4 and ABCC5. Meta-analysis showed an decreased risk of irinotecan-induced neutropenia in patients expressing ABCB1 2677G>T/G (odds ratio [OR]: 0.24; 95% CI: 0.1-0.59; p = 0.002) but increased risk for ABCC2 3972T>T (OR: 1.67; 95% CI: 1.01-2.74; p = 0.04). ABCG2 34G>A was associated with a threefold increased risk of irinotecan induced diarrhea (95% CI: 1.00-6.24; p = 0.05). CONCLUSION: The majority of studies have identified a role for variants in effluxdrug transporters in contributing to lung cancer treatment-associated ADRs. However, for implementation of use of these transporter genetic variants as prognostic markers for ADR risk, future studies must incorporate larger patient numbers. PMID- 27269637 TI - Of butterflies and wolves: enacting lupus transformations on the Internet. AB - This article explores how women with lupus use the Internet to construct discourses about illness and transformation. The textual and symbolic content of Internet websites and message boards offers unique perspectives on the relationship between embodied experience and textual construction, and demonstrates the ways in which women use their participation on the Internet to communicate about themselves. Using common search engines, an array of lupus websites were identified, including message boards and personal pages, and the textual and symbolic content was analysed for reoccurring themes. Three distinct types of transformational discourses were identified: adjustment narratives; expert narratives; and transformations of personhood. These transformations are achieved and given renewed value through online participation. The article suggests that online communication provides a unique opportunity to understand embodiment but also that transformational discourses may ultimately be limiting. PMID- 27269638 TI - The concept of 'mental trauma' and its transcultural application. AB - Impaired 'traumatic' memory of disaster-affected populations has come to the forefront of humanitarian work. In this article, the application of the notion of 'mental trauma' by psychosocial intervention programmes, relating to the tsunami disaster, will be critically examined. It will be shown in which type of theoretical structure the guidelines' notion of 'mental trauma' is rooted, presenting 'traumatic' experience as a division of the self, which is defined through agency and coherence. It will be argued that this entails a certain subjectivity of representation, which may not have transcultural validity. It is concluded that rehabilitation and development programmes after disasters have to integrate and address multiple levels, including community-level interventions, drawing on local coping strategies and resources. PMID- 27269639 TI - Eloquent bodies: conflict and ritual in northern Sri Lanka. AB - It is increasingly apparent that hostilities continue in the aftermath of war and conflict, where presuppositions of peace and safety are rarely reflected on the ground. In Sri Lanka, the 2002 ceasefire agreement between the Sri Lankan government and the Liberation Tigers of Tamil Eelam (LTTE) has recently collapsed. This collapse developed slowly over a period of several years, beginning with cautious optimism before descending into deep pessimism with increasingly high levels of violence brought about by the absence of any real progress. Efforts to rebuild and reintegrate both rural and urban communities in the north of the country have had to take place within an atmosphere of silence, suspicion and a marked escalation towards the renewed outbreak of war. This article, following sixteen months of fieldwork in the northern Jaffna peninsula, examines how Tamil youths - many of whom were imprisoned and tortured during the war - have transformed a well-known ritual that has seen a dramatic increase since occupation of the far north by government troops in 1996. The ritual, previously an act of devotion to a popular Tamil god, Murugan, has transformed into a demonstration of strength and youthful challenge. This article examines how toleration of ritual pain can be contrasted with the pain and suffering of war, and articulated not only for the self, but also for the entire community. PMID- 27269640 TI - Structural violence and emotional health: a message from Easington, a former mining community in northern England. AB - This discussion paper, written by a UK general practitioner and graduate student of anthropology, explores the uncomfortable relationship between institutionalised inequalities of wealth and opportunities, and emotional health, in a disadvantaged community in the north-east of England. The author begins by locating the thesis in the corpus of anthropological literature which acknowledges human suffering and refuses to adopt a position of cultural relativism. The complex and elusive phenomenon of structural violence is unpacked, followed by a description of the setting and the author's methodology. Clinical observations are presented as contextualised narratives located around three themes: alcohol misuse; gendered violence; and inter-generational violence. The vignettes portray how the consequences of institutionalised inequalities are manifest in the embodied and emotional lives of many who live in economically marginalised communities. The author concludes with a discussion of the dilemma at the heart of a morally engaged practitioner's clinical practice as one who eschews the dominant ideology of individual responsibility for health and recognises that agency is compromised by structural violence. PMID- 27269641 TI - Problems in the Latina paradox: measuring social support for pregnant immigrant women from Mexico. AB - Women who have immigrated to the United States from Mexico have better than expected birth outcomes. Part of this apparent health 'paradox' has been explained by high levels of social support which are thought to offset known risk factors for low birth weight. Yet common measures of social support during pregnancy suffer from presumptions of cultural homogeneity and a-priori definitions of meaningful social support. Analysis of qualitative data from ethnographic research with 28 low-income immigrant women from Mexico living in south Texas demonstrates that preferences for certain kinds of social support vary considerably, based on how each woman makes meaning of being pregnant. This diversity is one more piece of evidence that minority cultures cannot be essentialised in health disparities research. By not measuring the diversity of desire for different kinds of support, existing correlations between social support and birth outcomes may obscure other important psychosocial mediators, such as pregnancy-related social status, that could impact birth outcomes. Moreover, a measure of pregnancy-related status may offer a more thorough explanation of the 'protective effect' that could be explored independent of immigrant status. PMID- 27269642 TI - The anti-politics of health reform: household power relations and child health in rural Senegal. AB - This article employs ethnographic evidence from rural Senegal to explore two dimensions of health sector reform. First, it makes the case that health reforms intersect with and exacerbate existing social, political, and economic inequalities. Current equity analysis draws attention to the ways that liberal and utilitarian frameworks for health reform fail to achieve distributive justice. The author's data suggest that horizontal power relations within households and small communities are equally important for understanding health disparities and the effects of health reform. Second, the article explores how liberal discourses of health reform, particularly calls for 'state-citizen partnerships' and 'responsiblization', promote depoliticised understandings of health. Discourses associated with health reform paradoxically highlight individual responsibility for health while masking the ways that individual health practice is constrained by structural inequalities. PMID- 27269643 TI - Local perceptions of dengue fever in northeast Thailand and their implications for adherence to prevention campaigns. AB - The government of Thailand has invested heavily in community-based dengue fever prevention campaigns, yet community participation has been inadequate to prevent transmission. This ethnographic study explored local understandings of dengue in rural northeast Thailand, and their implications for adherence to government initiated prevention measures centred around mosquito control. While community members recognised the most severe manifestation of the disease - dengue haemorrhagic fever (DHF) - as life threatening, they were unaware of the existence of the milder form of dengue fever (DF) that makes up the majority of cases. Consequently, milder fevers were believed to be something other than dengue, such that dengue was perceived as a rare illness, hindering participation in prevention. Furthermore, a local illness category, khai mak mai ('fruit fever') complicated the diagnosis, treatment and prevention of dengue fever, as people viewed it as both difficult to distinguish from dengue, and untreatable by biomedicine. PMID- 27269644 TI - Mapping the body: tracing the personal and the political dimensions of HIV/AIDS in Khayelitsha, South Africa. AB - This article offers an analysis of the body-mapping dimension of the 'treatment literacy' initiatives of the Treatment Action Campaign (TAC), an HIV/AIDS-focused social movement in South Africa. It situates body mapping within the politics of HIV/AIDS activism in South Africa. The alliance between activists and biomedical practitioners is explored and the emphasis on the 'science of HIV' in TAC treatment literacy considered alongside the foregrounding of social realities, such as poverty and inequality. The article argues that the education activities of the TAC illustrate 'context-sensitive' science, rather than following a linear model of 'public understanding of science'. The personal accounts published alongside the first body maps are explored to illustrate an evident re socialisation of biological organs and an emphasis on the relationality of bodies. The bounded bodies and the activist emphasis on body politics become ways to counteract fears of the virulence of the illness. PMID- 27269646 TI - Does small for gestational age worsen outcomes in gestational diabetics? AB - OBJECTIVE: Our goal was to determine whether pregnancy outcomes are worse in gestational diabetics with small for gestational age (SGA) than those without. METHODS: This was a retrospective cohort study of 114 199 pregnancies with gestational diabetes mellitus (GDM) in California, 6446 of which were complicated by SGA. SGA was defined as birth weight < 10th percentile. Predictors included the presence or absence of SGA. Outcomes included respiratory distress syndrome (RDS), neonatal demise (NND), intrauterine fetal demise (IUFD), hypoglycemia and jaundice. The data were also stratified by gestational age looking at 32 + 0-36 + 6 weeks and 37 + 0-41 + 6 weeks. Univariate and multivariate analyses were performed. RESULTS: In the term 37 + 0 to 41 + 6 week GDM cohort the risk of RDS increased from 0.4% to 1.3%, the risk of neonatal demise from 0.02% to 0.09%, the risk of IUFD from 0.1% to 0.4%, the risk of hypoglycemia from 0.4% to 1.0% and the risk of jaundice from 18.0% to 23.3% (p < 0.001 for all). Similar relationships were seen in the 32 + 0 to 36 + 6 week group. The findings remained significant in multivariate analyses. CONCLUSIONS: The presence of SGA in a patient with gestational diabetes is associated with significantly increased risks of adverse outcomes compared to gestational diabetics without SGA including increased risks of RDS, neonatal demise, IUFD, hypoglycemia and jaundice. PMID- 27269645 TI - Applications and limitations of radiomics. AB - Radiomics is an emerging field in quantitative imaging that uses advanced imaging features to objectively and quantitatively describe tumour phenotypes. Radiomic features have recently drawn considerable interest due to its potential predictive power for treatment outcomes and cancer genetics, which may have important applications in personalized medicine. In this technical review, we describe applications and challenges of the radiomic field. We will review radiomic application areas and technical issues, as well as proper practices for the designs of radiomic studies. PMID- 27269647 TI - Recent progress for the selective pharmaceutical analyses using molecularly imprinted adsorbents and their related techniques: A review. AB - A well-organized molecularly imprinted polymer (MIP) provides the amazing selective molecular recognition ability, which have been close to natural enzymes and antibodies. One of the most efficient applications of MIPs is a selective separation and detection of pharmaceutical compounds in biological and/or environmental samples. MIP-based solid phase extraction now capacitates the selective concentration of the targeting compound from real samples. Also, many of the attractive methodological approaches and applications regarding the analysis of pharmaceutical samples using molecular imprinting technologies (MITs) have been reported in recent years. In this review, we summarize a part of the recent these works related to a new preparation concept of the adsorption adsorbents, sensitive sensor techniques, cell/bacteria separation, and drug delivery system. We believe that our concise summary will be of assistance to additional methodological MITs and highly selective separations/detections. PMID- 27269648 TI - Association of Rho-kinase Gene Polymorphisms with Respiratory Distress Syndrome in Preterm Neonates. AB - BACKGROUND: Respiratory distress syndrome (RDS) of the newborn is one of the most common causes of morbidity and mortality in preterm infants. Our objective was to determine the association between Rho-kinase (ROCK1 and ROCK2) gene polymorphisms and RDS in preterm neonates. METHODS: A total of 193 preterm infants with RDS and 186 preterm infants without respiratory problems were included in this study. Polymorphisms were analyzed in genomic DNA using a BioMark 96.96 dynamic array system. RESULTS: We observed that ROCK1 gene rs2271255 (Lys222Glu) and rs35996865 polymorphisms, and ROCK2 gene rs726843, rs2290156, rs10178332, and rs35768389 (Asp601Val) polymorphisms were associated with RDS. However, no associations were found with rs73963110, rs1515219, rs965665, rs2230774 (Thr431Asn), rs6755196, and rs10929732 polymorphisms. Additionally, 12 haplotypes (6 in ROCK1 and 6 in ROCK2) were found to be markedly associated with RDS. CONCLUSION: This is the first study to examine the involvement of ROCK gene variation in the risk of incident RDS. The results strongly suggest that ROCK gene polymorphisms may modify individual susceptibility to RDS in the Turkish population. PMID- 27269649 TI - The changing face of septic arthritis complicating rheumatoid arthritis in the era of biotherapies. Retrospective single-center study over 35years. AB - OBJECTIVES: To see whether the frequency and features of septic arthritis (SA) complicating rheumatoid arthritis (RA) have changed over the last 35years. METHODS: This retrospective single-center study included all patients hospitalized at the rheumatology department for SA bacteriologically documented by synovial fluid and/or blood culture samples. The periods 1979-2002 (before biotherapies) and 2003-2013 (the era of biotherapies) were compared. RESULTS: Between 1979 and 2013, 64/514 (12.5%) SA presented with a RA - 21/157 (13.4%) in the 2003-2013 period and 43/357 (12.0%) in the 1979-2002 period. Over the past decade, median age of RA SA patients increased (61 vs. 68 years; P<0.02) and predominant gender became males (52% vs. 40%). The features of the RA remained unchanged: history (18 vs. 16years), rheumatoid factor (95% vs. 87%), and corticosteroids (91% vs. 81%). Over the last decade 24% (vs. 0; P<0.003) of the patients received a biologic DMARD: etanercept (n=2), adalimumab (n=1), rituximab (n=1), tocilizumab (n=1). Proportion of polyarticular infection had decreased strongly (9.5% vs. 37%; P<0.02). Proportion of Staphyloccus aureus infections remained stable, but there was a higher incidence of MRSA infections (31 vs. 6%; P<0.05). Blood cultures less often tested positive (29% vs. 47%; NS). Case fatality rate had fallen slightly in RA SA (5% vs. 9%; NS), but not in non-RA SA cases (7% vs. 6%; NS). CONCLUSION: This study brings reassuring findings - in the era of biotherapies, the rate of septic arthritis amongst patients with RA has not increased, and the most severe septic polyarticular forms are on the decline. PMID- 27269650 TI - Comparison of the Big Five personality traits in fibromyalgia and other rheumatic diseases. AB - INTRODUCTION: The personality of patients with fibromyalgia is still under debate. Some studies found high neuroticism associated with low extraversion, while others found that these traits do not differ from the normal population. Personality factors intervene in the emotional regulation and modulation of pain. The aim of the study was to determine the personality traits of patients with fibromyalgia compared to other rheumatic diseases. METHODS: In a multicentric study, women with fibromyalgia, rheumatoid arthritis, spondyloarthritis or Sjogren's syndrome were asked to complete the Big Five Inventory, which encompasses five main personality dimensions, namely (1) extraversion vs. introversion, (2) agreeableness vs. antagonism, (3) conscientiousness vs. impulsivity, (4) neuroticism vs. emotional stability, and (5) openness vs. closed mindedness. Variance analysis (Student's t-test and ANOVA with post-hoc comparisons or Bonferroni correction) was performed. We also conducted hierarchical and non-hierarchical cluster analyses. RESULTS AND DISCUSSION: Participants were 163 women with fibromyalgia (n=48), rheumatoid arthritis (n=46), spondyloarthritis (n=46) and Sjogren's syndrome (n=23). The mean age was 47.18years (+/-10.81years, range 21 to 65). Patients with fibromyalgia had higher scores on agreeableness (F(3, 159)=3.39, P<0.05), neuroticism (F(3, 159)=3.79, P<0.05) and openness (F(3, 159)=4.32, P<0.01) than those with other rheumatic diseases. This study highlights the specificity of personality in fibromyalgia. It also underlines the protective role of personality traits: in the fibromyalgia group, high neuroticism and low conscientiousness (high impulsivity) were associated with a high level of chronic pain. PMID- 27269651 TI - Early treatment of reactive arthritis with etanercept and 2 years follow-up. PMID- 27269652 TI - A unilateral erosive arthritis in a patient with systemic lupus erythematosus. PMID- 27269653 TI - Varicella-Zoster virus hip arthritis in a rheumatoid arthritis patient. PMID- 27269654 TI - Use of FRAX((r)) in men. PMID- 27269655 TI - Raynaud's phenomenon of the tongue. PMID- 27269656 TI - "Puffy hand syndrome". AB - Intravenous drug addiction is responsible for many complications, especially cutaneous and infectious. There is a syndrome, rarely observed in rheumatology, resulting in "puffy hands": the puffy hand syndrome. We report two cases of this condition from our rheumatologic consultation. Our two patients had intravenous drug addiction. They presented with an edema of the hands, bilateral, painless, no pitting, occurring in one of our patient during heroin intoxication, and in the other 2 years after stopping injections. In our two patients, additional investigations (biological, radiological, ultrasound) were unremarkable, which helped us, in the context, to put the diagnosis of puffy hand syndrome. The pathophysiology, still unclear, is based in part on a lymphatic toxicity of drugs and their excipients. There is no etiological treatment but elastic compression by night has improved edema of the hands in one of our patients. PMID- 27269657 TI - Meeting the mental health needs of people with multiple sclerosis: a qualitative study of patients and professionals. AB - PURPOSE: To explore perspectives and experiences of people with multiple sclerosis (MS) and health care professionals of mental health support for MS in the UK. METHOD: 24 people with MS, 13 practice nurses, 12 general practitioners (GPs) and 9 MS specialist nurses were recruited through community groups and primary care practices across North West England. Semi-structured interviews were conducted, and data analyzed thematically using constant comparative analysis within and across the data sets. The theoretical framework of candidacy was used to interrogate data. RESULTS: Four themes were identified: candidates for care, management choices, defining roles, and permeability and responsiveness. DISCUSSION: Candidacy for care, and symptom management, depended on the framing of symptoms through a social or medical model of depression. Normalizing symptoms could prevent help-seeking by patients. Reported referral behavior varied by professional group, based on perceived remit, competency and training needs. GPs were perceived by patients and other professionals as central for management of mental health needs in MS, but may not perceive this role themselves, suggesting a need for increased knowledge, training, and improved access to specialist care. Implications for Rehabilitation Anxiety and depression are common in people with MS. Management of mental health needs in people with MS relies on complex decisions made by both people with MS and health care professionals. General practitioners may play a key role in the ongoing management of mental health needs of people with MS. PMID- 27269658 TI - Towards Leanness by 'Feeding' a Novel Thermogenic Pathway? AB - Upon activation, brown and beige adipocytes help to fight excessive fat in rodents, and their oxidative properties can be induced by cooling, capsinoids, and fish oil. New research now suggests that synergistic anti-obesity effects can be achieved by combining such strategies, and that a novel pathway mediates part of the effect. PMID- 27269659 TI - Newcastle disease virus infection induces activation of the NLRP3 inflammasome. AB - Inflammatory responses are important aspects of the innate immune system during virus infection. We found that Newcastle disease virus can induce inflammasome activation in the human macrophage-like cell line THP-1. Viral replication was required for inflammasome activation, and small hairpin RNA knockdown experiments indicated that IL-1beta secretion was mediated by the NLRP3 inflammasome. We also verified the results in LPS-primed bone marrow-derived macrophages (BMDMs) from NLRP3-deficient and wild type mice. NDV is considered to be a promising oncolytic virus. Stimulating the immune system has been proposed as a key mechanism of oncolytic specificity, and the inflammasome appears to be an important mechanism by which NDV is controlled. Knockdown of inflammasome components or chemical inhibition of caspase-1 activity shows that cell survival was augmented and benefited NDV replication. This study shows that NLRP3 inflammasome activation is an innate cellular response to NDV infection and offers insights into the oncolytic specificity of NDV. PMID- 27269660 TI - OBSTRUCTIVE SLEEP APNEA AND OFFICE-BASED SURGERY. PMID- 27269661 TI - Clinical Comparison: Fast-Acting and Traditional Topical Dental Anesthetic. AB - A randomized, nonblinded clinical trial compared the effectiveness of an application method of a fast-acting refrigerant topical agent to a 20% benzocaine gel topical. In a split-mouth design, right and left anterior middle superior alveolar injections (N = 30) were administered with a 27-gauge needle at least 24 hours apart with preinjection topicals. Using a cotton-tipped applicator, a refrigerant topical was applied for 5 seconds and 20% benzocaine gel for 2 minutes on opposite sides at 2 separate appointments. Subjects self-reported pain perception after each injection using a visual analog scale (VAS). The mean VAS ratings demonstrated no significant difference between the 5-second application of the refrigerant (M = 16.2, SD = 17.7) and the 2-minute application of 20% benzocaine topical gel anesthetic (M = 17.9, SD = 18.2). Fifty-seven percent of the subjects reported greater pain reduction with the refrigerant, 33% reported greater pain reduction with 20% benzocaine, and 10% reported no difference. Results suggest the described method of application of a refrigerant as an oral topical anesthetic has a faster onset and provides similar benefit in pain reduction compared with 20% benzocaine gel. The refrigerant was easy to accomplish and well received by subjects, indicating potential for routine use in dentistry. PMID- 27269662 TI - Rapid Deterioration of Basic Life Support Skills in Dentists With Basic Life Support Healthcare Provider. AB - The aim of this study was to investigate the correlation between basic life support skills in dentists who had completed the American Heart Association's Basic Life Support (BLS) Healthcare Provider qualification and time since course completion. Thirty-six dentists who had completed the 2005 BLS Healthcare Provider course participated in the study. We asked participants to perform 2 cycles of cardiopulmonary resuscitation on a mannequin and evaluated basic life support skills. Dentists who had previously completed the BLS Healthcare Provider course displayed both prolonged reaction times, and the quality of their basic life support skills deteriorated rapidly. There were no correlations between basic life support skills and time since course completion. Our results suggest that basic life support skills deteriorate rapidly for dentists who have completed the BLS Healthcare Provider. Newer guidelines stressing chest compressions over ventilation may help improve performance over time, allowing better cardiopulmonary resuscitation in dental office emergencies. Moreover, it may be effective to provide a more specialized version of the life support course to train the dentists, stressing issues that may be more likely to occur in the dental office. PMID- 27269663 TI - Female Patients Require a Higher Propofol Infusion Rate for Sedation. AB - Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery. PMID- 27269664 TI - Epinephrine Affects Pharmacokinetics of Ropivacaine Infiltrated Into Palate. AB - Pulpal anesthesia success rates for ropivacaine following maxillary infiltration anesthesia seem to be low. We investigated the hypothesis that the addition of epinephrine would affect the pharmacokinetics of ropivacaine by retaining ropivacaine in the mucosa of the injected area through the time-dependent distribution of ropivacaine in the rat maxilla and serum following maxillary infiltration anesthesia using (3)H-labeled ropivacaine. We then examined the vasoactivity of ropivacaine with or without epinephrine on local peripheral blood flow. The addition of epinephrine to ropivacaine increased ropivacaine concentrations in the palatal mucosa and adjacent maxilla by more than 3 times that of plain ropivacaine at 20 minutes. By observing the autoradiogram of (3)H ropivacaine, plain ropivacaine in the maxilla was remarkably reduced 20 minutes after injection. However, it was definitely retained in the palatal mucosa, hard palate, adjacent maxilla, and maxillary nerve after the administration with epinephrine. Ropivacaine with epinephrine significantly decreased labial blood flow. This study suggests that 10 MUg/mL epinephrine added to 0.5% ropivacaine could improve anesthetic efficacy and duration for maxillary infiltration anesthesia over plain ropivacaine. PMID- 27269665 TI - Anesthetic Management of a Patient With Charcot-Marie-Tooth Disease. AB - Charcot-Marie-Tooth disease (CMTD) is a hereditary peripheral neuropathy and is characterized by progressive muscle atrophy and motor-sensory disorders in all 4 limbs. Most reports have indicated that major challenges with general anesthetic administration in CMTD patients are the appropriate use of nondepolarizing muscle relaxants and preparation for malignant hyperthermia in neuromuscular disease. Moderate sedation may be associated with the same complications as those of general anesthesia, as well as dysfunction of the autonomic nervous system, reduced perioperative respiratory function, difficulty in positioning, and sensitivity to intravenous anesthetic agents. We decided to use intravenous sedation in a CMTD patient and administered midazolam initially and propofol continuously, with total doses of 1.5 mg and 300 mg, respectively. Anesthesia was completed in 3 hours and 30 minutes without adverse events. We suggest that dental anesthetic treatment with propofol and midazolam may be effective for patients with CMTD. PMID- 27269666 TI - Variant Inferior Alveolar Nerves and Implications for Local Anesthesia. AB - A sound knowledge of anatomical variations that could be encountered during surgical procedures is helpful in avoiding surgical complications. The current article details anomalous morphology of inferior alveolar nerves encountered during routine dissection of the craniofacial region in the Gross Anatomy laboratory. We also report variations of the lingual nerves, associated with the inferior alveolar nerves. The variations were documented and a thorough review of literature was carried out. We focus on the variations themselves, and the clinical implications that these variations present. Thorough understanding of variant anatomy of the lingual and inferior alveolar nerves may determine the success of procedural anesthesia, the etiology of pathologic processes, and the avoidance of surgical misadventure. PMID- 27269667 TI - General Anesthesia for a Patient With Pelizaeus-Merzbacher Disease. AB - We report the successful management of general anesthesia for a patient with Pelizaeus-Merzbacher disease (PMD). PMD is one of a group of progressive, degenerative disorders of the cerebral white matter. The typical clinical manifestations of PMD include psychomotor retardation, nystagmus, abnormal muscle tone, seizures, and cognitive impairment. General anesthesia for a patient with PMD may be difficult mainly because of seizures and airway complications related to poor pharyngeal muscle control. In addition, the possibility of exacerbation of spasticity should be considered. A 20-year-old man with PMD required removal of impacted wisdom teeth under general anesthesia. General anesthesia was induced with thiamylal, fentanyl, and desflurane. Anesthesia was maintained with desflurane and continuous intravenous remifentanil under bispectral index and train-of-4 monitoring. Anesthesia lasted 1 hour 20 minutes and was completed uneventfully. Airway complications, seizures, and exacerbation of spasticity did not occur postoperatively. Preoperatively, our patient had no history of epilepsy attacks or aspiration pneumonia, and no clinical symptoms of gastroesophageal reflux disease. Therefore, exacerbation of spasticity was one of the most likely potential complications. Identification of these associated conditions and evaluation of risk factors during preoperative examination is important for performing safe anesthesia in these patients. PMID- 27269668 TI - Management of Patients With Cardiovascular Implantable Electronic Devices in Dental, Oral, and Maxillofacial Surgery. AB - The prevalence of cardiovascular implantable electronic devices as life prolonging and life-saving devices has evolved from a treatment of last resort to a first-line therapy for an increasing number of patients. As these devices become more and more popular in the general population, dental providers utilizing instruments and medications should be aware of dental equipment and medications that may affect these devices and understand the management of patients with these devices. This review article will discuss the various types and indications for pacemakers and implantable cardioverter-defibrillators, common drugs and instruments affecting these devices, and management of patients with these devices implanted for cardiac dysrhythmias. PMID- 27269669 TI - Promoting interprofessional collaboration in oncology through a teamwork skills simulation programme. AB - Outcomes in clinical oncology can be improved when care is delivered by high performance teams. The purpose of the initiative described in this article was to develop interprofessional team training opportunities using simulated cancer care scenarios to enhance collaborative practice skills within clinical oncology. Scenarios were developed based on internal needs assessment and review of patient safety data. Paired teams of haematology-oncology nurses and fellows completed the patient management scenarios, followed by debriefing and performance feedback. Research design consisted of an observational case study and questionnaire of participants in a cross-sectional analysis. Twenty-three learners participated in two separate sessions. All participants responded with scores of 4-5 on a 5-point Likert scale regarding the perceived value of the training programme and its effectiveness in developing skills in teamwork and communication. Simulation-based team training scenarios were successfully implemented into an interprofessional curriculum for haematology-oncology nurses and fellows. Participants valued the experience and indicated that they acquired new knowledge, skills, and attitudes to enhance interprofessional collaboration in cancer care. These types of training programmes have the potential to transform cancer care by creating high-performing teams resulting in improved patient outcomes, enhanced clinical effectiveness, and higher levels of satisfaction among patients, families, and healthcare providers. PMID- 27269671 TI - Genetic modification of plant cell walls to enhance biomass yield and biofuel production in bioenergy crops. AB - Plant cell walls represent an enormous biomass resource for the generation of biofuels and chemicals. As lignocellulose property principally determines biomass recalcitrance, the genetic modification of plant cell walls has been posed as a powerful solution. Here, we review recent progress in understanding the effects of distinct cell wall polymers (cellulose, hemicelluloses, lignin, pectin, wall proteins) on the enzymatic digestibility of biomass under various physical and chemical pretreatments in herbaceous grasses, major agronomic crops and fast growing trees. We also compare the main factors of wall polymer features, including cellulose crystallinity (CrI), hemicellulosic Xyl/Ara ratio, monolignol proportion and uronic acid level. Furthermore, the review presents the main gene candidates, such as CesA, GH9, GH10, GT61, GT43 etc., for potential genetic cell wall modification towards enhancing both biomass yield and enzymatic saccharification in genetic mutants and transgenic plants. Regarding cell wall modification, it proposes a novel groove-like cell wall model that highlights to increase amorphous regions (density and depth) of the native cellulose microfibrils, providing a general strategy for bioenergy crop breeding and biofuel processing technology. PMID- 27269672 TI - Solution-Processed, Ultrathin Solar Cells from CdCl3(-)-Capped CdTe Nanocrystals: The Multiple Roles of CdCl3(-) Ligands. AB - Solution-processed CdTe solar cells using CdTe nanocrystal (NC) ink may offer an economically viable route for large-scale manufacturing. Here we design a new CdCl3(-)-capped CdTe NC ink by taking advantage of novel surface chemistry. In this ink, CdCl3(-) ligands act as surface ligands, sintering promoters, and dopants. Our solution chemistry allows obtaining very thin continuous layers of high-quality CdTe which is challenging for traditional vapor transport methods. Using benign solvents, in air, and without additional CdCl2 treatment, we obtain a well-sintered CdTe absorber layer from the new ink and demonstrate thin-film solar cells with power conversion efficiency over 10%, a record efficiency for sub-400 nm thick CdTe absorber layer. PMID- 27269670 TI - Reduced sleep spindle activity point to a TRN-MD thalamus-PFC circuit dysfunction in schizophrenia. AB - Sleep disturbances have been reliably reported in patients with schizophrenia, thus suggesting that abnormal sleep may represent a core feature of this disorder. Traditional electroencephalographic studies investigating sleep architecture have found reduced deep non-rapid eye movement (NREM) sleep, or slow wave sleep (SWS), and increased REM density. However, these findings have been inconsistently observed, and have not survived meta-analysis. By contrast, several recent EEG studies exploring brain activity during sleep have established marked deficits in sleep spindles in schizophrenia, including first-episode and early-onset patients, compared to both healthy and psychiatric comparison subjects. Spindles are waxing and waning, 12-16Hz NREM sleep oscillations that are generated within the thalamus by the thalamic reticular nucleus (TRN), and are then synchronized and sustained in the cortex. While the functional role of sleep spindles still needs to be fully established, increasing evidence has shown that sleep spindles are implicated in learning and memory, including sleep dependent memory consolidation, and spindle parameters have been associated to general cognitive ability and IQ. In this article we will review the EEG studies demonstrating sleep spindle deficits in patients with schizophrenia, and show that spindle deficits can predict their reduced cognitive performance. We will then present data indicating that spindle impairments point to a TRN-MD thalamus prefrontal cortex circuit deficit, and discuss about the possible molecular mechanisms underlying thalamo-cortical sleep spindle abnormalities in schizophrenia. PMID- 27269673 TI - Corrigendum to: "Is suicide an option?: The impact of disability on suicide acceptability in the context of depression, suicidality, and demographic factors" [J. Affect. Disord. 189 (2016) 25-35]. PMID- 27269674 TI - Differential CTX-M Expression from a Conserved Promoter: Role of Promoter Associated Spacer Sequences Downstream of the blaCTX-M Regulon. AB - AIMS: The aim of this project was to explore the different CTX-M expression levels occurring from a single conserved promoter with different spacer sequences, the variation of which is hypothesized to be a key factor in fluctuating levels of CTX-M. METHODS: The blaCTX-M promoter fragments with five different spacer sequences were amplified, sequenced and cloned into the pUA66 expression vector carrying the green fluorescent protein (GFP) gene. The expression of blaCTX-M in the transconjugants was analyzed using fluorescence microscopy, flow cytometry and qRT-PCR. RESULTS: The promoters of all the blaCTX M genes were provided by ISEcp1 and were extremely conserved. The promoter associated spacer sequences varied from 42 to 127 bp and variations in GFP expression in the five transconjugants were observed. A nucleic acid deletion and point mutation were detected in the spacer sequences by variations in which the expression of blaCTX-M was influenced. CONCLUSION: The different spacer sequences have a significant impact on the activity of the conserved promoter. The shorter spacer sequence between the conserved promoter and the blaCTX-M gene does not specifically enhance the expression of blaCTX-M, contrary to previous reports. The expression of blaCTX-M may be regulated by changes in promoter activity caused by diverse spacer sequences. PMID- 27269705 TI - Role of nanomaterials in plants under challenging environments. AB - The application of nanostructured materials, designed for sustainable crop production, reduces nutrient losses, suppresses disease and enhances the yields. Nanomaterials (NMs), with a particle size less than 100 nm, influence key life events of the plants that include seed germination, seedling vigor, root initiation, growth and photosynthesis to flowering. Additionally, NMs have been implicated in the protection of plants against oxidative stress as they mimic the role of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX). However, besides their beneficial effects on plants, applications of NMs have been proved to be phytotoxic too as they enhance the generation of reactive oxygen species (ROS). The elevated level of ROS may damage the cellular membranes, proteins and nucleic acids. Therefore, in such a conflicting and ambiguous nature of NMs in plants, it is necessary to decipher the mechanism of cellular, biochemical and molecular protection render by NMs under stressful environmental conditions. This review systematically summarizes the role of NMs in plants under abiotic stresses such as drought, salt, temperature, metal, UV-B radiation and flooding. Furthermore, suitable strategies adopted by plants in presence of NMs under challenging environments are also being presented. PMID- 27269708 TI - Is vaccenic acid (18:1t n-7) associated with an increased incidence of hip fracture? An explanation for the calcium paradox. AB - High calcium intake may increase hip fracture (HF) incidence. This phenomenon, known as the calcium paradox, might be explained by vaccenic acid (18:1t n-7, VA), the highly specific trans fatty acid (TFA) present in dairy products. First, we ecologically investigated the relationship between 18:1 TFA intake and HF incidence using data from 12 to 13 European countries collected before 2000; then we measured the effects of VA and elaidic acid (18:1t n-9, EA) on osteoblasts from goldfish scales (tissues very similar to mammalian bone), with alkaline phosphatase as a marker; and finally we measured the effect of VA on mRNA expression in the scales for the major bone proteins type I collagen and osteocalcin. HF incidence was significantly correlated with 18:1 TFA intake in men (r=0.57) and women (r=0.65). Incubation with 1MUmol/L VA and EA for 48h significantly decreased alkaline phosphatase activity by 25% and 21%, respectively. Incubation of scales with 10MUmol/L VA for 48h significantly decreased mRNA expression for type I collagen and osteocalcin (by about 50%). In conclusion, VA may be causatively related to HF and could explain the calcium paradox. It may be prudent to reduce 18:1 TFA intake, irrespective of trans positions, to prevent HF. PMID- 27269707 TI - A prospective, randomized, double blind, placebo-controlled evaluation of the effects of eicosapentaenoic acid and docosahexaenoic acid on the clinical signs and erythrocyte membrane polyunsaturated fatty acid concentrations in dogs with osteoarthritis. AB - BACKGROUND: Osteoarthritis (OA) in dogs is a prevalent and serious condition. The most common treatment for the clinical signs of OA in dogs is the administration of nonsteroidal antiiflammatory pharmaceuticals. Omega-3 (n-3) fatty acids have been shown to reduce the clinical signs of osteoarthritis in dogs. OBJECTIVE: The primary goals of this study were 1) to determine the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the clinical signs of OA in dogs, 2) to evaluate the effects of supplementation on the arachadonic acid (ARA)/ (EPA+DHA) algorithm and 3) to correlate alterations in the ARA/(EPA+DHA) with changes in the clinical signs of canine OA. METHODS: Seventy-eight client owned dogs were enrolled in a prospective, randomized, double-blind, placebo controlled clinical trial. Dogs were randomized to placebo oil or triglyceride n-3 oil (providing an average dose of 69mg EPA+DHA/kg/day). Orthopedic examinations and blood analyses were performed at baseline, day 42, and day 84. A single investigator confirmed a diagnosis of OA of the coxofemoral joints and/or stifle joints in all dogs. RESULTS: Seventy-four dogs completed the trial. All clinical outcomes for measuring discomfort, lameness, and joint severity at day 84 and all blood metrics at day 42 and day 84 significantly (p<0.05) improved compared with placebo. No major side effects were observed. CONCLUSION AND CLINICAL RELEVANCE: This study demonstrated that the daily supplementation of a dogs diet with EPA and DHA shifts the blood fatty acid concentrations correlating to relief of clinical signs associated with OA in dogs. PMID- 27269706 TI - Association Between Time to Rehabilitation and Outcomes After Traumatic Spinal Cord Injury. AB - OBJECTIVE: To examine the relations between time to rehabilitation after spinal cord injury (SCI) and rehabilitation outcomes at discharge and 1-year postinjury. DESIGN: Retrospective cohort study. SETTING: Facilities designated as Spinal Cord Injury Model Systems. PARTICIPANTS: Patients (N=3937) experiencing traumatic SCI between 2000 and 2014, who were 18 years or older, and who were admitted to a model system within 24 hours of injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch-transformed FIM motor score at discharge and 1-year postinjury, discharge to a private residence, and the Craig Handicap Assessment and Reporting Technique (CHART) Physical Independence and Mobility scores at 1 year postinjury. RESULTS: After accounting for health status, a 10% increase in time to rehabilitation was associated with a 1.50 lower FIM motor score at discharge (95% confidence interval [CI], -2.43 to -0.58; P=.001) and a 3.92 lower CHART Physical Independence score at 1-year postinjury (95% CI, -7.66 to -0.19; P=.04). Compared to the mean FIM motor score (37.5) and mean CHART Physical Independence score (74.7), the above-mentioned values represent relative declines of 4.0% and 5.3%, respectively. There was no association between time to rehabilitation and discharge to a private residence, 1-year FIM motor score, or the CHART mobility score. CONCLUSIONS: Earlier rehabilitation after traumatic SCI may improve patients' functional status at discharge. PMID- 27269709 TI - Dietary fat intake and red blood cell fatty acid composition of children and women from three different geographical areas in South Africa. AB - Dietary fat intake, particularly the type of fat, is reflected in the red blood cell (RBC) fatty acid (FA) profile and is vital in growth, development and health maintenance. The FA profile (%wt/wt) of RBC membrane phospholipids (as determined by gas chromatography) and dietary intake (as determined by 24h recall) was assessed in 2-6y old South African children and their caregivers randomly selected from three communities, i.e. an urban Northern Cape community (urban-NC; n=104), an urban coastal Western Cape community (urban-WC; n=93) and a rural Limpopo Province community (rural-LP; n=102). Mean RBC FA values across groups were compared using ANOVA and Bonferroni post-hoc test while controlling for age and gender (children); median dietary intake values were compared using a Kruskal Wallis test. Dietary intakes for total fat, saturated FAs and polyunsaturated FAs were higher in the two urban areas compared to the rural area. Total fat intake in rural-LP, and omega-3 FA dietary intake in all three areas were lower than the South African adopted guidelines. Dietary SFA intake in both urban areas was higher than recommended by South African guidelines; this was reflected in the RBC membrane FA profile. Rural-LP children had the lowest intake of omega-3 and omega-6 FAs yet presented with the highest RBC docosahexaenoic acid (DHA) profile and highest arachidonic acid percentage. Although differences observed in dietary fat intake between the two urban and the rural area were reflected in the RBC membrane total phospholipid FA profile, the lowest total fat and alpha-linolenic acid (ALA) intake by rural children that presented with the highest RBC DHA profile warrants further investigation. PMID- 27269710 TI - Higher omega-3 index and DHA status in pregnant women compared to lactating women - Results from a German nation-wide cross-sectional study. AB - INTRODUCTION: During pregnancy and lactation, there is a high need of long-chain (LC) omega-3 fatty acids (n-3 PUFA), especially docosahexaenoic acid (DHA), for fetus and infant. Also, a low LC n-3 PUFA status during pregnancy is associated with postpartum depression. The aim of this cross-sectional study was to analyze the LC n-3 PUFA status in German women during pregnancy and lactation. MATERIAL AND METHODS: As a part of a nationwide cross-sectional study in which the nutrient status of women in different stages of life was determined, 213 pregnant (>=27th week of gestation) and 127 lactating women between 18 and 44 years were evaluated regarding their LC n-3 PUFA status by measuring the omega-3 index (relative eicosapentaenoic acid (EPA) and DHA concentration in erythrocyte fatty acid). RESULTS: The mean omega-3 index of the total study population was 6.23+/ 1.48%. Pregnant women showed significant (p<=0.001) higher omega-3 index values (6.40+/-1.31%) and DHA concentrations (5.91+/-1.23%) than lactating women (omega 3 index: 5.50+/-1.34%; DHA: 4.79+/-1.27%). Woman with LC n-3 PUFA supplementation showed higher omega-3 index values (7.73+/-1.28%) vs. women without supplementation (6.04+/-1.39%, p<=0.001). Week of pregnancy, month of lactation as well as smoking were negatively associated with the omega-3 index. CONCLUSION: Comprehensive data on the long-term LC n-3 PUFA status of German women during pregnancy and lactation are presented. To evaluate an optimal maternal omega-3 index in view of the fetal and infant development further studies are needed. PMID- 27269711 TI - Dairy fat blend improves brain DHA and neuroplasticity and regulates corticosterone in mice. AB - Mimicking the breast milk lipid composition appears to be necessary for infant formula to cover the brain's needs in n-3 PUFA. In this study, we evaluated the impact of partial replacement of vegetable oil (VL) in infant formula by dairy fat (DL) on docosahexaenoic acid (DHA) brain level, neuroplasticity and corticosterone in mice. Mice were fed with balanced VL or balanced DL diets enriched or not in DHA and arachidonic acid (ARA) from the first day of gestation. Brain DHA level, microglia number, neurogenesis, corticosterone and glucocorticoid receptor expression were measured in the offsprings. DL diet increased DHA and neuroplasticity in the brain of mice at postnatal day (PND) 14 and at adulthood compared to VL. At PND14, ARA and DHA supplementation increased DHA in VL but not in DL mice brain. Importantly, DHA and ARA supplementation further improved neurogenesis and decreased corticosterone level in DL mice at adulthood. In conclusion, dairy lipids improve brain DHA level and neuroplasticity. PMID- 27269712 TI - Differential modulation of the lipid metabolism as a model for cellular resistance to fumonisin B1-induced cytotoxic effects in vitro. AB - Differential sensitivity of primary hepatocytes and Chang cells to the cancer promoter fumonisin B1 (FB1)-induced cytotoxic effects were investigated in relation to changes in membrane lipid distribution. In contrast to primary hepatocytes, Chang cells were resistant to FB1-induced cytotoxic effects. This was associated with a high cholesterol (Chol) and sphingomyelin (SM) and low phosphatidylcholine (PC) content, resulting in a significant (P<0.05) decrease in phosphatidylethanolamine (PE)/PC ratio, increased Chol/total phosphoglyceride (TPG) ratios and low total polyunsaturated fatty acids (PUFA) content in PC and PE, suggesting a more rigid membrane structure. High levels of C18:1 and reduced polyunsaturated fatty acid (PUFA) levels are likely to provide selective resistance to FB1-induced oxidative stress. FB1-associated lipid changes included decreases in SM and Chol, increases in sphinganine (Sa) and PE with the increases in key saturated, monounsaturated, and PUFAs in PE as key role players in the differential responses to FB1-induced cell growth responses in cells. PMID- 27269714 TI - Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells. AB - Previous studies have demonstrated that exposure to a maternal cafeteria diet during the lactation period alone produces detrimental effects to offspring metabolic health comparable to exposure during the entire perinatal period. The present study used a rodent model to assess the effect of a maternal cafeteria diet on the fat content and fatty acid composition of the dams' milk, and to determine the degree to which this was related to the fatty acid status of offspring on postnatal day 1 (PND1), weaning and 3 weeks post-weaning onto a standard rodent diet. As expected, omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) content of both the milk and pup red blood cells (RBCs) was lower in the cafeteria (CAF) group on PND1. At 2 weeks post-partum, milk produced by CAF dams had a higher total fat, saturated fat and n-6 PUFA content, however these differences were modest in comparison with the differences in maternal intake between groups. Offspring suckled by CAF dams had a lower n-3 LCPUFA and n-6 PUFA status at weaning and higher trans fatty acid levels at both weaning and 6 weeks of age. These findings indicate that the fat content and fatty acid composition of the dam's milk is altered by exposure to a cafeteria diet. While it appears that the dam has a significant capacity to buffer the transfer of most dietary lipids into the milk, the trans fatty acids in particular appear to be readily transferred, resulting in persistent increases in trans fatty acid status of the offspring after weaning. The potential physiological implications of this warrants further examination. PMID- 27269713 TI - Long-chain polyunsaturated fatty acid status in children, adolescents and adults with phenylketonuria. AB - BACKGROUND: Patients with phenylketonuria have been reported to be deficient in long-chain polyunsaturated fatty acids (LCPUFAs). It has been postulated that good compliance with the dietary regimen negatively influences LCPUFA status. METHODS: In 36 patients with phenylketonuria and 18 age-matched healthy control subjects LCPUFA-levels in plasma phospholipids and cholesteryl esters, erythrocyte phosphatidylcholine and phosphatidylethanolamine were evaluated. RESULTS: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels did not differ significantly between patients and control subjects in plasma and erythrocyte fractions. There was a significant negative correlation between SDS (standard deviation) scores of DHA-levels in erythrocyte parameters from the respective age-matched control group and patients' concurrent and long-term phenylalanine levels for erythrocyte phosphatidylethanolamine and erythrocyte phosphatidylcholine. Patients with lower (higher) phenylalanine levels had positive (negative) DHA-SDS. CONCLUSION: In contrast to previous reports we did not find lower LCPUFA-levels in patients with phenylketonuria compared to age matched healthy control subjects. Good dietary control was associated with better LCPUFA status. PMID- 27269715 TI - Association of polyunsaturated fatty acids in breast milk with fatty acid desaturase gene polymorphisms among Chinese lactating mothers. AB - BACKGROUND: The fatty acid desaturase (FADS) controls polyunsaturated fatty acid (PUFA) synthesis in human tissues and breast milk. DESIGN: Evaluate the influence of 10 single nucleotide polymorphisms (SNPs) and various haplotypes in the FADS gene cluster (FADS1, FADS2, FADS3) on PUFA concentration in the breast milk of 209 healthy Chinese women. PUFA concentrations were measured in breast milk using gas chromatography and genotyping was performed using the Sequenom Mass Array system. RESULTS: A SNP (rs1535) and 2-locus haplotypes (rs3834458-rs1535, rs1535 rs174575) in the FADS2 gene were associated with concentrations of gamma-linoleic acid (GLA) and arachidonic acid (AA) in breast milk. Likewise, in the FADS1 gene, a 2-locus constructed haplotype (rs174547-rs174553) also affected GLA and AA concentration (P<0.05 for all). Minor allele carriers of the SNP and haplotypes described above had lower concentrations of GLA and AA. In the FADS2 gene, the 3 locus haplotype rs3834458-rs1535-rs174575, significantly affected concentrations of GLA but not AA. Pairwise comparison showed that individuals major homozygous for the SNP rs1000778 in the FADS3 gene had lower concentrations of ALA and linoleic acid (LA) in their breast milk. CONCLUSION: Polymorphisms in the FADS gene cluster influence PUFA concentrations in the breast milk of Chinese Han lactating women. PMID- 27269717 TI - Fossil pigments. AB - Johan Lindgren introduces fossil pigments. PMID- 27269716 TI - Synchrotron-Based Infrared Microanalysis of Biological Redox Processes under Electrochemical Control. AB - We describe a method for addressing redox enzymes adsorbed on a carbon electrode using synchrotron infrared microspectroscopy combined with protein film electrochemistry. Redox enzymes have high turnover frequencies, typically 10-1000 s(-1), and therefore, fast experimental triggers are needed in order to study subturnover kinetics and identify the involvement of transient species important to their catalytic mechanism. In an electrochemical experiment, this equates to the use of microelectrodes to lower the electrochemical cell constant and enable changes in potential to be applied very rapidly. We use a biological cofactor, flavin mononucleotide, to demonstrate the power of synchrotron infrared microspectroscopy relative to conventional infrared methods and show that vibrational spectra with good signal-to-noise ratios can be collected for adsorbed species with low surface coverages on microelectrodes with a geometric area of 25 * 25 MUm(2). We then demonstrate the applicability of synchrotron infrared microspectroscopy to adsorbed proteins by reporting potential-induced changes in the flavin mononucleotide active site of a flavoenzyme. The method we describe will allow time-resolved spectroscopic studies of chemical and structural changes at redox sites within a variety of proteins under precise electrochemical control. PMID- 27269718 TI - The insect central complex. AB - Hordes of tourists flock to Washington, D.C. every spring to see the cherry trees blossom. Once in the city, they must find their way to the Tidal Basin where the Japanese trees grow. Fortunately, a number of visual landmarks can help them to navigate. In 1910, the United States Congress passed The Height of Buildings Act, limiting the elevation of commercial and residential structures in D.C. to 130 feet. Thus, the 555-foot-tall Washington Monument often looms large against the horizon, serving as an anchor point to help set the tourists' sense of direction. Once their heading is set, they can lose sight of the monument behind buildings or groups of tall Scandinavian visitors and still use their internal compass to navigate to the Basin. This compass keeps track of their paces and turns and updates their sense of where they are and where they need to go. Yet while their heading informs their actions, it does not dictate them. Tourists who have been to D.C. in the past can, for example, use remembered views to alter their routes to avoid crowds. On an even finer scale, their leg movements also depend on their current state - they might increase the frequency and length of their strides if hunger pangs compete with their desire to see cherry blossoms, for example. The way in which these disparate cues and motivations influence exploration is a neuroscience mystery across creatures large and small. PMID- 27269719 TI - Dendrogramma is a siphonophore. AB - Dendrogramma was the iconic deep-sea animal of 2014, voted among the top-ten new species described that year [1]. The two species described are mushroom shaped animals, diploblastic, with an apparent gastrovascular system that extends from the base of the stalk to bifurcating canals that radiate through the flat disc [2]. The authors could not assign the new genus to any known animal group with certainty, leading to numerous media reports that it belonged to an entirely new phylum. Here we use phylogenomic data from newly collected specimens to show that Dendrogramma is a cnidarian, specifically a benthic siphonophore in the family Rhodaliidae. Although an entire Dendrogramma colony has not been found, we hypothesise that the mushroom-like bodies are bracts, possibly used to aid buoyancy or as defensive appendages to protect feeding gastrozooids or gonads. PMID- 27269720 TI - Time dilates after spontaneous blinking. AB - Accumulating evidence from pharmacology, neuroimaging, and genetics indicates that striatal dopamine influences time perception [1-5]. Despite these converging results, it is not known whether endogenous variations in dopamine underlie transient fluctuations in our perception of time. Here, we exploited the finding that striatal dopamine release is associated with an increase in spontaneous eye blink rate [6-8] to examine the relationship between intra-individual fluctuations in dopamine and interval timing. In two studies, participants overestimated visual subsecond and suprasecond and auditory subsecond intervals if they had blinked on the previous trial. These results are consistent with the hypothesis that transient fluctuations in striatal dopamine contribute to intra individual variability in time perception. PMID- 27269721 TI - Insect Orientation: The Travails of Going Straight. AB - A study of dung beetles rolling dung balls to safety reveals unexpected facets of the beetle's acquisition and use of celestial information for keeping to a straight path. PMID- 27269722 TI - Gradient Sensing: Engineering the Yeast Love Affair. AB - A new study in fission yeasts promotes the notion that transient polarity patches that wander the cell surface at the onset of mating are discrete agents of gradient sensing. This concept unexpectedly bridges the modes of gradient sensing in eukaryotes and prokaryotes. PMID- 27269723 TI - Palaeobiology: Born and Gone in Global Warming. AB - Why ichthyosaurs - marine Mesozoic reptiles - disappeared before the dinosaur extinction has remained a mystery. New research suggests they may have gone extinct stepwise, during one of the most extreme greenhouse periods in the history of complex life-forms. PMID- 27269724 TI - Myelination: Both Mindful and Mindless? AB - The amount of myelin that forms on individual axons can vary considerably. Recent work, including a new study, indicates that myelin profiles on distinct subclasses of axons might be determined by diverse mechanisms. PMID- 27269725 TI - Neuroendocrinology: Electromagnetogenetic Control over Feeding and Glucose Metabolism. AB - Cutting-edge experiments show a new means to control the activity of specifically genetically targeted neurons in the hypothalamus using electromagnetic force. At the flip of a switch, the system bidirectionally regulates feeding behavior and glucose homeostasis, demonstrating wireless control over deep brain regions and their strong influence over energy balance. PMID- 27269726 TI - Cell Biology: ERADicating Survival with BOK. AB - Mechanistic insights into the function of the pro-apoptotic BCL-2 family member BOK have remained elusive. A recent study shows that healthy cells constitutively degrade BOK via the ER-associated degradation and ubiquitin-proteasome pathways; following proteasome inhibition, BOK is stabilized to initiate a unique pro apoptotic death program. PMID- 27269727 TI - Sex Allocation: L'Enfer C'est les Autres? AB - Brine shrimp produce a maladaptive excess of sons when co-occurring with females from a related parthenogenetic species. Still, this sex ratio may be adaptive if, by mating with females of the other species, males miss out on mating with their own. PMID- 27269728 TI - Parental Care: When the Sex Has to Stop. AB - How is sexual conflict during reproduction resolved when parents collaborate to rear offspring? A new study shows that female burying beetles communicate their hormonal status to their male partners to avoid costly superfluous mating, using an anti-aphrodisiac pheromone. PMID- 27269729 TI - Pre-administration of PepFect6-microRNA-146a nanocomplexes inhibits inflammatory responses in keratinocytes and in a mouse model of irritant contact dermatitis. AB - The skin is a difficult to access tissue for efficient delivery of large and/or charged macromolecules, including therapeutic DNA and RNA oligonucleotides. Cell penetrating peptide PepFect6 (PF6) has been shown to be suitable transport vehicle for siRNAs in cell culture and systemically in vivo in mice. MiR-146a is known as anti-inflammatory miRNA that inhibits multiple factors from the nuclear factor (NF)-kappaB pathway in various cell types, including keratinocytes. In this study, PF6 was shown to form unimodal nanocomplexes with miR-146a mimic that entered into human primary keratinocytes, where miR-146a inhibited the expression of its direct targets from the NF-kappaB pathway and the genes known to be activated by NF-kappaB, C-C motif ligand (CCL)5 and interleukin (IL)-8. The transfection of miR-146a mimic with PF6 was more efficient in sub-confluent keratinocyte cultures, affected keratinocyte proliferation less and had similar effect on cell viability when compared with a lipid based agent. Subcutaneous pre administration of PF6-miR-146a nanocomplexes attenuated ear-swelling and reduced the expression of pro-inflammatory cytokines and chemokines IL-6, CCL11, CCL24 and C-X-C motif ligand 1 (CXCL1) in a mouse model of irritant contact dermatitis. Our data demonstrates that PF6-miR-146a nanoparticles might have potential in the development of therapeutics to target inflammatory skin diseases. PMID- 27269730 TI - MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson's disease. AB - Modulation of the subventricular zone (SVZ) neurogenic niche can enhance brain repair in several disorders including Parkinson's disease (PD). Herein, we used biocompatible and traceable polymeric nanoparticles (NPs) containing perfluoro 1,5-crown ether (PFCE) and coated with protamine sulfate to complex microRNA-124 (miR-124), a neuronal fate determinant. The ability of NPs to efficiently deliver miR-124 and prompt SVZ neurogenesis and brain repair in PD was evaluated. In vitro, miR-124 NPs were efficiently internalized by neural stem/progenitors cells and neuroblasts and promoted their neuronal commitment and maturation. The expression of Sox9 and Jagged1, two miR-124 targets and stemness-related genes, were also decreased upon miR-124 NP treatment. In vivo, the intracerebral administration of miR-124 NPs increased the number of migrating neuroblasts that reached the granule cell layer of the olfactory bulb, both in healthy and in a 6 hydroxydopamine (6-OHDA) mouse model for PD. MiR-124 NPs were also able to induce migration of neurons into the lesioned striatum of 6-OHDA-treated mice. Most importantly, miR-124 NPs proved to ameliorate motor symptoms of 6-OHDA mice, monitored by the apomorphine-induced rotation test. Altogether, we provide clear evidences to support the use of miR-124 NPs as a new therapeutic approach to boost endogenous brain repair mechanisms in a setting of neurodegeneration. PMID- 27269732 TI - Mitochondrial functions in stem cells. AB - Mitochondria fulfill multiple cellular functions beyond ATP production, including several functions that are specialized for distinct tissue types (thermogenesis, steroidogenesis). Recent evidence indicates that mitochondrial activities are regulated within cell lineages, and through incompletely understood mechanisms, are important for specification of cell fate. Stem cells represent the apex of cell lineages, capable of self-renewal and multi-potential differentiation into cells with limited proliferative capacity, and are of intense interest in regenerative medicine. Examples of stem cells include embryonic stem cells and adult somatic stem cells. Tumor-initiating cells are also often described as cancer stem cells. For all of these cell types, the association of mitochondrial bioenergetic function or other mitochondrial phenotypes raises interesting questions about the regulation of 'stemness'. PMID- 27269731 TI - Mitochondrial pyruvate carrier function and cancer metabolism. AB - Metabolic reprogramming in cancer supports the increased biosynthesis required for unchecked proliferation. Increased glucose utilization is a defining feature of many cancers that is accompanied by altered pyruvate partitioning and mitochondrial metabolism. Cancer cells also require mitochondrial tricarboxylic acid cycle activity and electron transport chain function for biosynthetic competency and proliferation. Recent evidence demonstrates that mitochondrial pyruvate carrier (MPC) function is abnormal in some cancers and that increasing MPC activity may decrease cancer proliferation. Here we examine recent findings on MPC function and cancer metabolism. Special emphasis is placed on the compartmentalization of pyruvate metabolism and the alternative routes of metabolism that maintain the cellular biosynthetic pools required for unrestrained proliferation in cancer. PMID- 27269733 TI - Childhood Victimization, Internalizing Symptoms, and Substance Use Among Women Who Identify as Mostly Heterosexual. AB - PURPOSE: The current article examines substance use behavior and associated factors that contribute to risk of substance misuse, such as history of childhood victimization and reports of internalizing symptoms among women from various sexual identity subgroups. METHODS: We recruited a convenience sample of 332 community and university student women (M age = 20.88). Approximately 61.1% of the sample (n = 203) identified as exclusively heterosexual (or "straight"; EH) at the time of the survey, whereas 21.4% (n = 71) identified as primarily heterosexual (or "mostly heterosexual"), 6.6% (n = 22) as bisexual (or "equally gay/lesbian and heterosexual"), 3.0% (n = 10) as primarily gay/lesbian (or "mostly gay/lesbian") and 7.8% (n = 26) as exclusively gay/lesbian. RESULTS: Mostly heterosexual women were more likely than EH women to report childhood physical abuse and lifetime tobacco and marijuana use. Mostly heterosexual women also had higher levels of past-year alcohol use disorder symptomology, recent tobacco and marijuana use, and depressive symptoms. Mostly heterosexual women were more likely than bisexual women to have ever tried marijuana, although, among lifetime users, bisexual women reported more frequent recent use. CONCLUSION: Mostly heterosexual women reported levels of pathological alcohol use, lifetime rates of tobacco and marijuana use, and recent depressive symptoms that were higher than EH women and relatively similar to lesbian and mostly lesbian women. Bisexual women reported heavier current use of marijuana and were more likely than mostly heterosexual women to report childhood sexual abuse. Implications for mental health services for clients who identify as non-EH are discussed. PMID- 27269734 TI - Mapping and ablation procedures for the treatment of ventricular tachycardia. AB - INTRODUCTION: Ventricular tachycardia (VT) may occur in the presence or absence of structural heart disease. Given that the management of VT hinges on the presence of symptoms and risk of sudden cardiac death (SCD), the main treatment goals are elimination of symptoms (including frequent implantable cardioverter defibrillator [ICD] therapies) and prevention of SCD. Unfortunately, medical management is suboptimal in a significant proportion of patients. As such, ablative therapy plays a prominent role in the treatment of ventricular tachycardia. AREAS COVERED: In this review, we will discuss various VT disorders that are encountered in patients with and without structural heart disease. Further, we will highlight salient features regarding mapping and ablation of the various VT syndromes. Finally, we will discuss what lies on the horizon for VT ablation. Expert commentary: Meticulous mapping should aim to find the region that is most likely to be successful and least likely to result in a complication. Although recognition of the various mechanisms of VT, familiarity with different methods to mapping and ablation, and awareness of potential limitations of current approaches is critical, a thorough understanding of the fundamental principles and nuances of each facet within EP is required to ensure optimal outcomes for our patients. PMID- 27269736 TI - The radiology informed consent form: recommendations from the European Society of Cardiology position paper. AB - Every radiological and nuclear medicine examination confers a definite long-term risk of cancer, but most patients undergoing such examinations receive no or inaccurate information about radiation dose and corresponding risk related to the dose received. Informed consent is a procedure to support (not substitute) the physician/patient dialogue and relationship, facilitating a free, informed and aware expression of the patient's will in the principle of patient autonomy. Physicians are responsible for providing patients with all the information on risks, benefits and alternatives useful to the patient to make the decision. In current radiological practice the information on the radiation dose and long-term cancer risks is difficult to find and not easy to understand. The form using plain language should spell-out the type of examination, the effective dose (mSv), the effective dose expressed in number of chest radiographs and the risk of cancer. The current practice clashes against the guidelines and the law. PMID- 27269737 TI - Copper-Catalyzed Aerobic Enantioselective Cross-Dehydrogenative Coupling of N Aryl Glycine Esters with Terminal Alkynes. AB - A copper-catalyzed enantioselective cross-coupling of a Csp3-H moiety (N-aryl glycine ester) with a Csp-H component (terminal alkyne) using molecular oxygen as the terminal oxidant is described for the first time. The sustainable method provides an efficient and environmentally friendly approach to rapidly prepare a diverse array of optically active non-natural alpha-amino acids. PMID- 27269738 TI - Chemical Reactivity Perspective into the Group 2B Metals Halides. AB - Chemical reactivity descriptors within the conceptual density functional theory can be used to understand the nature of the interactions between two monomers of the Group 2B metal halides. This information might be valuable in the development of adequate force law parameters for simulations in the liquid state. In this study, MX2 monomers and dimers, where M = Zn, Cd, Hg and X = F, Cl, Br, I, were investigated in terms of chemical reactivity descriptors. Relativistic effects were taken into account using the effective core potential (ECP) approach. Correlations were produced between global and local reactivity descriptors and dimerization energies. Results presented in this work represent the first systematic investigation of Group 2B metal halides in the literature from a combined point of view of both relativistic effects and chemical reactivity descriptors. Steric effects were found to be responsible for the deviation from the chemical reactivity principles. They were introduced into the chemical reactivity descriptors such as local softness. PMID- 27269735 TI - Engineered matrices for skeletal muscle satellite cell engraftment and function. AB - Regeneration of traumatically injured skeletal muscles is severely limited. Moreover, the regenerative capacity of skeletal muscle declines with aging, further exacerbating the problem. Recent evidence supports that delivery of muscle satellite cells to the injured muscles enhances muscle regeneration and reverses features of aging, including reduction in muscle mass and regenerative capacity. However, direct delivery of satellite cells presents a challenge at a translational level due to inflammation and donor cell death, motivating the need to develop engineered matrices for muscle satellite cell delivery. This review will highlight important aspects of satellite cell and their niche biology in the context of muscle regeneration, and examine recent progresses in the development of engineered cell delivery matrices designed for skeletal muscle regeneration. Understanding the interactions of muscle satellite cells and their niche in both native and engineered systems is crucial to developing muscle pathology-specific cell- and biomaterial-based therapies. PMID- 27269739 TI - Immunotherapy for small-cell lung cancer. PMID- 27269740 TI - Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial. AB - BACKGROUND: Concurrent administration of the immune checkpoint inhibitors nivolumab and ipilimumab has shown greater efficacy than either agent alone in patients with advanced melanoma, albeit with more high-grade adverse events. We assessed whether sequential administration of nivolumab followed by ipilimumab, or the reverse sequence, could improve safety without compromising efficacy. METHODS: We did this randomised, open-label, phase 2 study at nine academic medical centres in the USA. Eligible patients (aged >=18 years) with unresectable stage III or IV melanoma (treatment-naive or who had progressed after no more than one previous systemic therapy, with an Eastern Cooperative Oncology Group performance status of 0 or 1) were randomly assigned (1:1) to induction with intravenous nivolumab 3 mg/kg every 2 weeks for six doses followed by a planned switch to intravenous ipilimumab 3 mg/kg every 3 weeks for four doses, or the reverse sequence. Randomisation was done by an independent interactive voice response system with a permuted block schedule (block size four) without stratification factors. After induction, both groups received intravenous nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. The primary endpoint was treatment-related grade 3-5 adverse events until the end of the induction period (week 25), analysed in the as-treated population. Secondary endpoints were the proportion of patients who achieved a response at week 25 and disease progression at weeks 13 and 25. Overall survival was a prespecified exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT01783938, and is ongoing but no longer enrolling patients. FINDINGS: Between April 30, 2013, and July 21, 2014, 140 patients were enrolled and randomly assigned to nivolumab followed by ipilimumab (n=70) or to the reverse sequence of ipilimumab followed by nivolumab (n=70), of whom 68 and 70 patients, respectively, received at least one dose of study drug and were included in the analyses. The frequencies of treatment-related grade 3-5 adverse events up to week 25 were similar in the nivolumab followed by ipilimumab group (34 [50%; 95% CI 37.6-62.4] of 68 patients) and in the ipilimumab followed by nivolumab group (30 [43%; 31.1-55.3] of 70 patients). The most common treatment-related grade 3-4 adverse events during the whole study period were colitis (ten [15%]) in the nivolumab followed by ipilimumab group vs 14 [20%] in the reverse sequence group), increased lipase (ten [15%] vs 12 [17%]), and diarrhoea (eight [12%] vs five [7%]). No treatment-related deaths occurred. The proportion of patients with a response at week 25 was higher with nivolumab followed by ipilimumab than with the reverse sequence (28 [41%; 95% CI 29.4-53.8] vs 14 [20%; 11.4-31.3]). Progression was reported in 26 (38%; 95% CI 26.7-50.8) patients in the nivolumab followed by ipilimumab group and 43 (61%; 49.0-72.8) patients in the reverse sequence group at week 13 and in 26 (38%; 26.7-50.8) and 42 (60%; 47.6-71.5) patients at week 25, respectively. After a median follow-up of 19.8 months (IQR 12.8-25.7), median overall survival was not reached in the nivolumab followed by ipilimumab group (95% CI 23.7-not reached), whereas over a median follow-up of 14.7 months (IQR 5.6-23.9) in the ipilimumab followed by nivolumab group, median overall survival was 16.9 months (95% CI 9.2-26.5; HR 0.48 [95% CI 0.29-0.80]). A higher proportion of patients in the nivolumab followed by ipilimumab group achieved 12-month overall survival than in the ipilimumab followed by nivolumab group (76%; 95% CI 64-85 vs 54%; 42-65). INTERPRETATION: Nivolumab followed by ipilimumab appears to be a more clinically beneficial option compared with the reverse sequence, albeit with a higher frequency of adverse events. FUNDING: Bristol-Myers Squibb. PMID- 27269742 TI - Sequential immunotherapy regimens-expect the unexpected. PMID- 27269741 TI - Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. AB - BACKGROUND: Treatments for small-cell lung cancer (SCLC) after failure of platinum-based chemotherapy are limited. We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens. METHODS: The SCLC cohort of this phase 1/2 multicentre, multi-arm, open-label trial was conducted at 23 sites (academic centres and hospitals) in six countries. Eligible patients were 18 years of age or older, had limited-stage or extensive-stage SCLC, and had disease progression after at least one previous platinum-containing regimen. Patients received nivolumab (3 mg/kg bodyweight intravenously) every 2 weeks (given until disease progression or unacceptable toxicity), or nivolumab plus ipilimumab (1 mg/kg plus 1 mg/kg, 1 mg/kg plus 3 mg/kg, or 3 mg/kg plus 1 mg/kg, intravenously) every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks. Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg. Depending on tolerability, patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. The primary endpoint was objective response by investigator assessment. All analyses included patients who were enrolled at least 90 days before database lock. This trial is ongoing; here, we report an interim analysis of the SCLC cohort. This study is registered with ClinicalTrials.gov, number NCT01928394. FINDINGS: Between Nov 18, 2013, and July 28, 2015, 216 patients were enrolled and treated (98 with nivolumab 3 mg/kg, three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg). At database lock on Nov 6, 2015, median follow up for patients continuing in the study (including those who had died or discontinued treatment) was 198.5 days (IQR 163.0-464.0) for nivolumab 3 mg/kg, 302 days (IQR not calculable) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 361.0 days (273.0-470.0) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 260.5 days (248.0-288.0) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. An objective response was achieved in ten (10%) of 98 patients receiving nivolumab 3 mg/kg, one (33%) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 14 (23%) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and ten (19%) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. Grade 3 or 4 treatment related adverse events occurred in 13 (13%) patients in the nivolumab 3 mg/kg cohort, 18 (30%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort, and ten (19%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase (none vs 5 [8%] vs none) and diarrhoea (none vs 3 [5%] vs 1 [2%]). No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment related adverse event. Six (6%) patients in the nivolumab 3 mg/kg group, seven (11%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group, and four (7%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events. Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events (myasthenia gravis and worsening of renal failure), and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis. INTERPRETATION: Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC. These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 randomised controlled trials in SCLC. FUNDING: Bristol-Myers Squibb. PMID- 27269743 TI - Transcriptional profiling of mitochondria associated genes in prefrontal cortex of subjects with major depressive disorder. AB - OBJECTIVES: Recent evidences suggest that mitochondrial dysfunction maybe involved in the pathophysiology of major depressive disorder (MDD); however, the role of mitochondrial genes in this disorder has not been studied systematically. In the present study, we profiled expression of mitochondrial genes in dorsolateral prefrontal cortex (dlPFC) of MDD and non-psychiatric control subjects. METHODS: Human mitochondrial RT2 profile PCR array plates were used to examine differentially expressed genes in dlPFC of 11 MDD and 11 control subjects. Differentially expressed genes were validated independently by qRT-PCR. Biological relevance of differentially expressed genes was analysed by gene ontology (GO) and ingenuity pathways analysis (IPA). RESULTS: We found that 16 genes were differentially expressed in the MDD group compared with control group. Among them, three genes were downregulated and 13 genes upregulated. None of these genes were affected by confounding variables, such as age, post-mortem interval, brain pH, and antidepressant toxicology. Seven differentially expressed genes were successfully validated in MDD subjects. GO and IPA analyses identified several new regulatory networks associated with mitochondrial dysfunctions in MDD. CONCLUSIONS: Our findings suggest abnormal mitochondrial systems in the brain of MDD subjects which could be involved in the etiopathogenesis of this disorder. PMID- 27269744 TI - Harnessing the power of networks: the future of perioperative research. PMID- 27269745 TI - Improving the care of patients with gastrointestinal bleeding. PMID- 27269747 TI - The role of plastic surgery in reconstruction after oncological surgery. AB - One in three people is affected by cancer in their lifetime. Surgical treatment commonly has the greatest impact on long-term survival, so a large proportion of patients undergo major oncological resection. This is the first in a symposium of four articles describing plastic surgical reconstruction after oncological resection. PMID- 27269748 TI - Breast reconstruction: options post-mastectomy. AB - Breast cancer is the most common cancer affecting women in the UK. Breast reconstruction after resection of breast cancers increases patients' quality of life and psychosocial functioning. This article introduces this field and explores the options available to patients with breast cancer. PMID- 27269749 TI - Head and neck reconstruction. AB - Head and neck cancers are among the rarer types of cancer presenting in the UK. However, oncological resection can cause significant morbidity in these patients, so reconstruction has a crucial role in the management of such patients to improve their postoperative quality of life. PMID- 27269750 TI - Overview of gynaecological and colorectal reconstruction. AB - Plastic surgeons are often required to reconstruct defects following radical pelvic surgery for advanced or recurrent anorectal and gynaecological malignancies. This article describes the most commonly used flaps for reconstruction following radical pelvic surgery and provides a treatment algorithm to facilitate decision making. PMID- 27269751 TI - Changes to the law on consent following Montgomery vs Lanarkshire Health Board. AB - The Supreme Court's determination on Montgomery (AP) (Appellant) v Lanarkshire Health Board (Respondent) (Scotland) [2015] clarified UK law on consent. It is for the informed patient to determine which intervention, if any, they will undergo. All doctors must meet this standard and may need to reassess their practice to do so. PMID- 27269752 TI - Contemporary interpretation of informed consent: autonomy and paternalism. AB - The Supreme Court's decision in the Montgomery case has questioned what is meant by 'informed consent'. Clinicians must establish who is a reasonable patient and exactly what they want to know. Obtaining informed consent requires a relationship to be built between patient and clinician and must respect patient autonomy. PMID- 27269753 TI - The interplay between heart failure, metabolism and body composition. AB - A complex interplay exists between heart failure, metabolic status and body composition. The idiosyncrasies of these relationships are poorly understood, but they offer prognostic value and potential clinical utility. Current understanding of this relationship and known clinical value are discussed in this article. PMID- 27269754 TI - Artifact simulating supracondylar femoral fracture on computed tomography. PMID- 27269755 TI - Dominique Jean Larrey: Napoleon's surgeon. PMID- 27269756 TI - In the footsteps of Dominique Larrey. PMID- 27269757 TI - Odd turns in adult life: voltage-gated potassium channel antibody syndrome. PMID- 27269758 TI - Congenital absence of inferior vena cava: an overlooked cause of deep vein thrombosis. PMID- 27269759 TI - Autoimmune haemolytic anaemia is a rare association with primary biliary cirrhosis. PMID- 27269760 TI - Skin lesions in calciphylaxis. PMID- 27269761 TI - Diagnostic capacity of tests used for knee examinations. PMID- 27269763 TI - Should neuromuscular blockers be used for every paediatric intubation? PMID- 27269764 TI - Whipple's disease. PMID- 27269765 TI - Percutaneous gastrostomy: troubleshooting complications. PMID- 27269766 TI - What is HFE haemochromatosis? PMID- 27269767 TI - Visual Discomfort While Viewing Three-dimensional Television as a Screening Tool for Pediatric Eye Diseases in Children. AB - PURPOSE: To investigate the efficacy of evaluating 3D asthenopia and 3D perception difficulty for screening of binocular vision abnormalities in children. METHODS: Patients aged 6-12 years with abnormal binocularity, including strabismus, amblyopia, and anisometropia, were included. Age-matched normal subjects without any ophthalmologic abnormality other than a refractive error were also recruited. The best-corrected visual acuity, refractive error, angle of strabismus, and stereopsis were measured. Presenting visual acuity (PVA) was measured as the uncorrected visual acuity for subjects without glasses and spectacle-corrected visual acuity for those with glasses. After watching 3D TV for 30 min, a survey was administered to evaluate the 3D perception and 3D asthenopia. Receiver operation characteristic (ROC) curve analysis was conducted to evaluate the efficacy of the survey for detecting abnormal binocularity and poor PVA. RESULTS: One hundred subjects were enrolled in this study. Among them, 59 had abnormal binocularity (strabismus, anisometropia, or amblyopia), and 41 were normal control. Among the entire subjects, the number of subjects with a PVA of 20/40 or worse in one or both eyes was 24 (7 from the normal control and 17 with abnormal binocularity). ROC curve analysis revealed that the survey did not effectively detect strabismus, anisometropia, or amblyopia. However, for detection of PVA 20/40 or worse in the subjects with abnormal binocularity, the total score of the survey yielded an area of 0.714 under the ROC curve (p = 0.010). The sensitivity was 88.2% and specificity was 61.9% with a cutoff at 0.50. CONCLUSION: The degree of 3D asthenopia and 3D perception while watching 3D TV were not effective for screening of abnormal binocularity. However, evaluation of the severity of 3D asthenopia and the quality of 3D perception can help screen of decrease in PVA that requires correction. PMID- 27269768 TI - Symptoms, functioning and coping strategies in individuals with schizophrenia spectrum disorders who do not take antipsychotic medication: a comparative interview study. AB - BACKGROUND: A considerable proportion of people with schizophrenia spectrum disorders do not take antipsychotic medication but seem to be functioning well. However, little is known about this group. To test the assumption that absence of medication is compensated for by more effective coping and increased social support, this study compared symptoms, functioning, coping strategies and social support in non-medicated and medicated individuals with schizophrenia spectrum disorders. METHOD: In all, 48 participants with a DSM-IV schizophrenia spectrum disorder who were taking (n = 25) or not taking antipsychotic medication (n = 23) were included. Assessment consisted of self-ratings of symptoms, symptom-related distress and social support combined with a semi-structured interview that assessed general and social functioning, subjective evaluation of symptoms and coping strategies. RESULTS: Symptom severity and distress did not differ between the groups. However, the non-medicated participants had significantly higher levels of general functioning than medicated participants and a longer duration of being non-medicated was significantly associated with a higher level of general functioning. In contrast to the hypotheses, not taking medication was not associated with more effective coping strategies or with higher levels of social support. Medicated participants more frequently reported the use of professional help as a coping strategy. CONCLUSIONS: Our results corroborate previous studies finding improved functioning in individuals with schizophrenia spectrum disorders who do not take medication compared with those who take medication, but do not support the notion that this difference is explicable by better coping or higher levels of social support. Alternative explanations and avenues for research are discussed. PMID- 27269769 TI - Single-step simple ROC curve fitting via PCA. AB - A simple approach to fitting curves to receiver operating characteristic rating data is presented. It is based on the first principal component of the covariance space of the inverse normal integral of the cumulative rating data of the targets and distractors. It provides for 2 new associated d' estimates, dp' and dYNp'. A Monte Carlo simulation demonstrated that the parameter estimates are unbiased and produce estimates comparable to the iterative, maximum likelihood approach. The corresponding computational and plotting functions in the R programming language are also provided. (PsycINFO Database Record PMID- 27269770 TI - [Ultrasound as a part of the student curriculum]. PMID- 27269771 TI - [Bites of venomous snakes in Switzerland]. AB - Although snake bites are rare in Europe, there are a constant number of snake bites in Switzerland. There are two domestic venomous snakes in Switzerland: the aspic viper (Vipera aspis) and the common European adder (Vipera berus). Bites from venomous snakes are caused either by one of the two domestic venomous snakes or by an exotic venomous snake kept in a terrarium. Snake- bites can cause both a local and/or a systemic envenoming. Potentially fatal systemic complications are related to disturbances of the hemostatic- and cardiovascular system as well as the central or peripheral nervous system. Beside a symptomatic therapy the administration of antivenom is the only causal therapy to neutralize the venomous toxins. PMID- 27269773 TI - [Ultrasound training in the medical curriculum at the Bern University - a pilot project]. PMID- 27269774 TI - [Zurich Sono4You]. PMID- 27269775 TI - [Dyspepsia, Ulcer Disease - Helicobacter pylori, Gastroesophageal Reflux Disease]. AB - Prevalence of H. pylori (HP) is declining, whereas reflux disease and the proportion of non-steroidal antiinflammatory drugs (NSAR) to HP-induced ulcers increase. Eradication heals HP-ulcer disease, interrupts cancerous progression and can improve dyspeptic symptoms. NSAR-ulcers heal under proton pump inhibitor (PPI) therapy but tend to recur after reexposition. Anticoagulants and antiplatlet agents increase the risk additionally. PPI reduces NSAR-ulcer recurrence. Reflux patients with severe inflammation and complications often need long-term therapy. Barrett's esophagus patients are at risk of esophageal adenocarcinoma. PMID- 27269776 TI - [Management of Type 2 Diabetes: a Practical Approach]. AB - Over the last years, the therapeutic aims for patients with type 2 diabetes have changed and several novel drugs have been introduced. In this Mini-Review we discuss these aims and how to achieve them. PMID- 27269777 TI - [Unusual Migraine Manifestations]. AB - Migraine is a complex neurologic disorder by which several systems of the central nervous system (autonomous system, affective, cognitive, sensoric and motoric system) may be affected on different levels. Around a fourth of the patients have migraine aura. The most common aura is the visual aura, followed by sensoric aura. But motoric deficits as well as deficits of higher cortical centers (disorders of thinking, orientation, coherence or concentration) may occur as well. In analogy with a headache calendar, an aura calendar can deliver important help in the diagnostic process of rare migraine manifestations and prevent underdiagnosis of unusual migraine manifestations. Complex migraine manifestations are diagnoses of exlusion, and a broad diagnostic work-up is warranted in order to exclude dangerous neurologic pathologies. There are no specific therapeutic recommendations, as there is a lack of randomized controlled studies. PMID- 27269778 TI - [Dysphagia and Sonography: what Association?]. AB - Achalasia is a primary esophageal motility disorder characterized by dysphagia, chest pain, and drug-resistant reflux symptoms. A detailed anamnesis and esophageal manometry are essential tools for a correct diagnosis. We present a case of a 31 years old woman with typical achalasia symptoms misdiagnosed for many years due to a complex background picture. Despite the evolution in medical sciences, this clinical case underlines the cornerstones of medical profession: patient-physician relation and bedside clinical approach. At the same time, it confirms the increasing role of ultrasonography as a simple but essential tool for a complete general-internal medicine evaluation. PMID- 27269780 TI - [Mindfulness-based stress reduction is effective in patients with chronic lumbar backache]. PMID- 27269779 TI - [Goodpasture Syndrome: a Rare Cause of Acute Anuric Renal Failure]. AB - We report a case of a 68 year old male who presented with an acute onset of anuric renal failure. Investigations revealed a histologically confirmed "double positive" anti-GBM disease with initially undetectably high antibody values. An induction therapy with plasma exchange, cyclophosphamide and initially high dose steroids and further maintenance therapy for three months was initiated. The patient remained dialysis-dependent despite partial recovering of renal function. Without pulmonary involvement there were no clues for Goodpasture's disease. Renal prognosis is unfavourable. PMID- 27269781 TI - [Months of antibiotic therapy in persistent symptoms of Lyme disease without effect]. PMID- 27269783 TI - [CME-EKG: Stress induced presyncopes]. PMID- 27269787 TI - Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca). AB - Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify "insults" and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL 17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The immunologic knowledge derived from longitudinal immunologic studies in killer whales, as was the target of the present study, has the potential to improve diagnostics and health related decision making for this and other domestic and free-ranging cetacean species. PMID- 27269788 TI - An ELISA for quantifying quail IgY and characterizing maternal IgY transfer to egg yolk in several quail strains. AB - In avian species, maternal blood immunoglobulin Y (IgY) is transferred to the egg yolks of maturing oocytes, but the mechanism underlying this transfer is unknown. To gain insight into the mechanism of maternal IgY transfer in quail, we established an enzyme-linked immunosorbent assay (ELISA) for the quantitation of quail IgY. We characterized strain differences in blood and egg yolk IgY concentrations and exogenously injected IgY-Fc uptakes into egg yolks. A specific rabbit polyclonal antibody to quail IgY was raised for the ELISA. Blood and egg yolk IgY concentrations were determined in six quail strains (one inbred strain, L; four closed population strains, AWE, DB, PS, WE; one commercial strain, Commercial). The birds were also injected with digoxigenin-labeled quail IgY-Fc, and its uptakes into laid eggs were compared. The strain difference in blood and egg yolk IgY concentrations was at most 2.5-fold, between PS and AWE. The rank order of IgY concentrations was AWE, Commercial, DB, L>=WE>=PS. A significant positive correlation (|R|=0.786) between individual blood IgY and egg yolk IgY and the concentrated egg yolk IgY (1.5-2-fold) against blood IgY was observed. Interestingly, there was a significant inverse correlation (|R|=0.452) between injected IgY-Fc uptakes and the blood IgY concentration, implying competition of the injected IgY-Fc and blood IgY in the process of IgY uptake into egg yolks. In conclusion, we successfully determined blood and egg yolk IgY concentrations in various quail strains by a quail IgY-specific ELISA. The concentrated egg yolk IgY against the blood IgY and the inverse relationship of exogenous IgY-Fc uptake against the blood IgY supports the existence of a selective IgY transport mechanism in avian maturing oocytes. PMID- 27269786 TI - NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene. AB - We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor cell lines, PANC-1 and A375-SM, survived after injection into these SCID pigs, but, as we demonstrate here, these cells, as well as K562 tumor cells, can be lysed in vitro by NK cells from SCID and non-SCID pigs. NK cells from both SCID and non-SCID pigs required activation in vitro with either recombinant human IL-2 or the combination of recombinant porcine IL-12 and IL-18 to kill tumor targets. We also showed that SCID NK cells could be activated to produce perforin, and perforin production was greatly enhanced in NK cells from both SCID and non-SCID pigs after IL-2 cytokine treatment. While CD16+, CD172- NK cells constituted an average of only 4% in non-SCID pigs, NK cells averaged 27% of the peripheral blood mononuclear cell population in SCID pigs. We found no significant differences in killing activity per NK cell between SCID and non-SCID pigs. We conclude that survival of human cancer cells in these SCID pigs is not due to an intrinsic defect in NK cell killing ability. PMID- 27269789 TI - Genome-wide association study for host response to bovine leukemia virus in Holstein cows. AB - The mechanisms of leukemogenesis induced by bovine leukemia virus (BLV) and the processes underlying the phenomenon of differential host response to BLV infection still remain poorly understood. The aim of the study was to screen the entire cattle genome to identify markers and candidate genes that might be involved in host response to bovine leukemia virus infection. A genome-wide association study was performed using Holstein cows naturally infected by BLV. A data set included 43 cows (BLV positive) and 30 cows (BLV negative) genotyped for 54,609 SNP markers (Illumina Bovine SNP50 BeadChip). The BLV status of cows was determined by serum ELISA, nested-PCR and hematological counts. Linear Regression Analysis with a False Discovery Rate and kinship matrix (computed on the autosomal SNPs) was calculated to find out which SNP markers significantly differentiate BLV-positive and BLV-negative cows. Nine markers reached genome wide significance. The most significant SNPs were located on chromosomes 23 (rs41583098), 3 (rs109405425, rs110785500) and 8 (rs43564499) in close vicinity of a patatin-like phospholipase domain containing 1 (PNPLA1); adaptor-related protein complex 4, beta 1 subunit (AP4B1); tripartite motif-containing 45 (TRIM45) and cell division cycle associated 2 (CDCA2) genes, respectively. Furthermore, a list of 41 candidate genes was composed based on their proximity to significant markers (within a distance of ca. 1 Mb) and functional involvement in processes potentially underlying BLV-induced pathogenesis. In conclusion, it was demonstrated that host response to BLV infection involves nine sub-regions of the cattle genome (represented by 9 SNP markers), containing many genes which, based on the literature, could be involved to enzootic bovine leukemia progression. New group of promising candidate genes associated with the host response to BLV infection were identified and could therefore be a target for future studies. The functions of candidate genes surrounding significant SNP markers imply that there is no single regulatory process that is solely targeted by BLV infection, but rather the network of interrelated pathways is deregulated, leading to the disruption of the control of B-cell proliferation and programmed cell death. PMID- 27269790 TI - A chimeric protein comprising the immunogenic domains of Mannheimia haemolytica leukotoxin and outer membrane protein PlpE induces antibodies against leukotoxin and PlpE. AB - Mannheimia haemolytica is a very important pathogen of pneumonia in ruminants. Bighorn sheep (BHS, Ovis canadensis) are highly susceptible to M. haemolytica caused pneumonia which has significantly contributed to the drastic decline of bighorn sheep population in North America. Pneumonia outbreaks in wild BHS can cause mortality as high as 90%. Leukotoxin is the critical virulence factor of M. haemolytica. In a 'proof of concept' study, an experimental vaccine containing leukotoxin and surface antigens of M. haemolytica developed by us induced 100% protection of BHS, but required multiple booster injections. Vaccination of wild BHS is difficult. But they can be vaccinated at the time of transplantation into a new habitat. Administration of booster doses, however, is impossible. Therefore, a vaccine that does not require booster doses is necessary to immunize BHS against M. haemolytica pneumonia. Herpesviruses are ideal vectors for development of such a vaccine because of their ability to undergo latency with subsequent reactivation. As the first step towards developing a herpesvirus vectored vaccine, we constructed a chimeric protein comprising the leukotoxin neutralizing epitopes and the immuno-dominant epitopes of the outer membrane protein PlpE. The chimeric protein was efficiently expressed in primary BHS lung cells. The immunogenicity of the chimeric protein was evaluated in mice before inoculating BHS. Mice immunized with the chimeric protein developed antibodies against M. haemolytica leukotoxin and PlpE. More importantly, the anti-leukotoxin antibodies effectively neutralized leukotoxin-induced cytotoxicity. Taken together, these results represent the successful completion of the first step towards developing a herpesvirus-vectored vaccine for controlling M. haemolytica pneumonia in BHS, and possibly other ruminants. PMID- 27269791 TI - Impact of oral meloxicam and long-distance transport on cell-mediated and humoral immune responses in feedlot steers receiving modified live BVDV booster vaccination on arrival. AB - The objective of this study was to investigate the impact of oral meloxicam (MEL) and long-distance transportation on cell-mediated immunity (CMI) in preconditioned steers receiving a booster vaccination on arrival. We hypothesized that steers treated with MEL at 1mg/kg body weight, 6h before night-time transport, would be less immunocompromised on arrival (day 0) and after 7days, and that CMI following vaccination with a modified live bovine viral diarrhea virus (BVDV) recall antigen would be increased. Brahman crossbreed steers, 13-17 months of age (n=87), were randomly assigned to one of four treatment groups: MEL, transported (MTR) (n=22), MEL, non-transported (MNT) (n=22), lactose placebo, transported (CTR) (n=21), and lactose placebo, non-transported (CNT) (n=22). MTR and CTR steers were transported for approximately 16h non-stop on a truck from Mississippi to Iowa (approximately 1300km), whereas steers in the MNT and CNT groups remained in Mississippi as non-transported controls. Body weight was measured and jugular blood was collected at -1, 0, and 7days from all steers at the same time, regardless of location. Multi-parameter flow cytometry (MP-FCM) was used to identify T-cell subsets and detect the expression of three activation markers (CD25 [interleukin (IL)-2 receptor], intracellular interferon-gamma [IFNgamma], and IL-4) after in vitro stimulation with BVDV recall antigen. Plasma cortisol concentration was measured on day -1, 0, and 7 as a marker of transport associated stress. Serum antibody titer to BVDV was assessed on day -1 and day 7 post-booster vaccination. Whole-blood samples were analyzed using MP-FCM on days 0 and 7. Results were log transformed and analyzed using repeated measures of analysis of variance. Compared with non-transported controls, transport led to an increase in BVDV-induced expression of CD25, IFNgamma, and IL-4 in CD4(+), CD8(+), and gammadelta(+) T-cell subsets (P<0.05). MEL treatment mitigated the transportation-associated increase in CD25 expression by peripheral blood mononuclear cells (PBMCs), CD4(+), and gammadelta(+) T cells. CMI outputs for the MTR group were less than those of the CTR group (P<0.05); however, the MTR and NT groups did not differ (P>0.10). A treatment*transport interaction was noted for the increase in IL-4 expression by CD8(+) T cells after transport, with a significant difference between the CTR and MTR groups at day 7. In conclusion, the use of oral MEL prior to transport appears to have inhibitory or homeostatic effects, but further research is needed to validate the effect of MEL treatment on specific T-cell subsets in transported cattle. PMID- 27269792 TI - In situ hybridization to detect and localize signature cytokines of T-helper (Th) 1 and Th2 immune responses in chicken tissues. AB - The avian immune system has been shown to possess a repertoire of cytokines directing T-helper (Th) 1 and Th2 types of immune responses similar to that in mammals. The objective of this study was to establish in situ hybridization (ISH) for the localization of mRNA of selected signal cytokines, chicken interferon gamma (ChIFN-gamma), chicken interleukin (ChIL)-4 and ChIL-13 in fixed tissues. RNA probes were generated to hybridize to 488, 318, and 417bp of the respective target mRNA. Probe concentrations ranging from 100ng/ml to 400ng/ml were shown to be suitable to label cells that expressed these cytokines. The specificity of every probe was verified using the respective sense probe. ChIFN-gamma, ChIL-4 and ChIL-13 positive cells were observed in the lymphocytic infiltrations of liver and in the periarteriolar lymphatic sheaths of spleen collected from specific-pathogen-free chickens. ISH of these cytokines in a severely inflamed liver due to infiltration with the parasite Histomonas meleagridis revealed the expression of both ChIFN-gamma and ChIL-13 mRNA in the mononuclear infiltrates. In conclusion, ChIFN-gamma, ChIL-4 and ChIL-13 mRNA were efficiently localized by ISH, which supplies a valid technique to characterize immune responses in fixed tissues. PMID- 27269793 TI - Response of immune response genes to adjuvants poly [di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP), CpG oligodeoxynucleotide and emulsigen at intradermal injection site in pigs. AB - Understanding the mechanisms by which adjuvants mediate their effects provide critical information on how innate immunity influences the development of adaptive immunity. Despite being a critical vaccine component, the mechanisms by which adjuvants mediate their effects are not fully understood and this is especially true when they are used in large animals. This lack of understanding limits our ability to design effective vaccines. In the present study, we administered polyphosphazene (PCEP), CpG oligodeoxynucleotides (CpG), emulsigen or saline via an intradermal injection into pigs and assessed the impact on the expression of reported 'adjuvant response genes' over time. CpG induced a strong upregulation of the chemokine CXL10 several 'Interferon Response Genes', as well as TNFalpha, and IL-10, and a down-regulation of IL-17 genes. Emulsigen upregulated expression of chemokines CCL2 and CCL5, proinflammatory cytokines IL 6 and TNFalpha, as well as TLR9, and several IFN response genes. PCEP induced the expression of chemokine CCL2 and proinflammatory cytokine IL-6. These results suggest that emulsigen and CpG may promote recruitment of innate immune cells and Th1 type cytokine production but that PCEP may promote a Th-2 type immune response through the induction of IL-6, an inducer of B cell activity and differentiation. PMID- 27269794 TI - Expectancy Effect in Three Mind-Body Clinical Trials. AB - Expectancy, arguably the prime component of the placebo effect, has been shown to significantly modify the effects of many treatments. Furthermore, various forms of mind-body interventions have demonstrated effective improvements in outcomes. The aim of this study was to examine the relationship between pretreatment expectations and symptom reduction in a secondary analysis of 3 mind-body intervention programs. An adjusted correlation and regression analysis compared data from a 6-question expectancy questionnaire to a self-reported clinical impression of change score. Only 1 of the 6 expectancy questions in 1 of the 3 studies reached significance (B = 0.087; P = .025). The combined data from all 3 studies did not reveal significant expectancy effects. The positive effects of mindfulness meditation appear to be independent of an expectancy effect. PMID- 27269795 TI - Remote home management for chronic kidney disease: A systematic review. AB - Background Remote home management is a new healthcare model that uses information technology to enhance patients' self-management of disease in a home setting. This study is designed to identify the effects of remote home management on patients with chronic kidney disease (CKD). Methods A comprehensive search of PubMed, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was performed in January 2015. The reference listings of the included articles in this review were also manually examined. Randomized controlled trials (RCTs) designed to evaluate the effects of remote home management on patients with CKD were included. Results Eight trials were identified. The results of this study suggest that the quality of life (QOL) enabled by remote home management was higher than typical care in certain dimensions. However, the effects of remote home management on blood pressure (BP) remain inconclusive. The studies that assessed health service utilization demonstrated a significant decrease in hospital readmission, emergency room visits, and number of days in the hospital. Another favorable result of this study is that regardless of their gender, age or nationality, patients tend to comply with remote home management programs and the use of related technologies. Conclusions The available data indicate that remote home management may be a novel and effective disease management strategy for improving CKD patients' QOL and influencing their attitudes and behaviors. And, relatively little is known about BP and cost-effectiveness, so future research should focus on these two aspects for the entire population of patients with CKD. PMID- 27269808 TI - An Effective Virtual Screening Protocol To Identify Promising p53-MDM2 Inhibitors. AB - The p53-MDM2 interaction is a well-known protein-protein contact, and its disruption is a key event for p53 activation and induction of its oncosuppressor response. The design of small molecules that can block the p53-MDM2 interaction and reactivate the p53 function is a promising strategy for cancer therapy. To date, several compounds have been identified as p53-MDM2 inhibitors, and X-ray structures of MDM2 complexed with several ligands are available in the Brookhaven Protein Data Bank. These data have been exploited to compile a hierarchical virtual screening protocol. The first steps were aimed at selecting a focused library, which was submitted in parallel to docking and pharmacophore model alignment. Selected compounds were subjected to inhibition assays of both cellular vitality (MTT) and p53-MDM2 interaction (ELISA and co immunoprecipitation), disclosing four nanomolar inhibitors. PMID- 27269809 TI - Quantitative description of short-range order and its influence on the electronic structure in Ag-Pd alloys. AB - We investigate the effect of short-range order (SRO) on the electronic structure in alloys from the theoretical point of view using density of states (DOS) data. In particular, the interaction between the atoms at different lattice sites is affected by chemical disorder, which in turn is reflected in the fine structure of the DOS and, hence, in the outcome of spectroscopic measurements. We aim at quantifying the degree of potential SRO with a proper parameter. The theoretical modeling is done with the Korringa-Kohn-Rostoker Green's function method. Therein, the extended multi-sublattice non-local coherent potential approximation is used to include SRO. As a model system, we use the binary solid solution Ag c Pd1-c at three representative concentrations c = 0.25, 0.5 and 0.75. The degree of SRO is varied from local ordering to local segregation through an intermediate completely uncorrelated state. We observe some pronounced features, which change over the whole energy range of the valence bands as a function of SRO in the alloy. These spectral variations should be traceable in modern photoemission experiments. PMID- 27269810 TI - Successful treatment of Panton-Valentine leukocidin-positive methicillin resistant Staphylococcus aureus pneumonia with high doses of linezolid administered in continuous infusion. PMID- 27269811 TI - Construction of a Defined Biomimetic Matrix for Long-Term Maintenance of Mouse Induced Pluripotent Stem Cells. AB - The existing in vitro culture systems often use undefined and animal-derived components for the culture of pluripotent stem cells. Artificial bioengineered peptides have the potential to become alternatives to these components of extracellular matrix (ECM). Integrins and cadherins are two cell adhesion proteins important for stem cell self-renewal, differentiation, and phenotype stability. In the present study, we sought to mimic the physico-biochemical properties of natural ECMs that allow self-renewal of mouse induced pluripotent stem cells (iPSCs). We develop a genetically engineered ECM protein (ERE-CBP) that contains (i) an integrin binding peptide sequence (RGD/R), (ii) an E-/N cadherin binding peptide sequence (SWELYYPLRANL/CBP), and (iii) 12 repeats of APGVGV elastin-like polypeptides (ELPs/E).While ELPs allow efficient coating by binding to nontreated hydrophobic tissue culture plates, RGD/R and CBP support integrin- and cadherin-dependent cell attachment, respectively. Mouse iPSCs on this composite matrix exhibit a more compact phenotype compared to cells on control gelatin substrate. We also demonstrated that the ERE-CBP supports proliferation and long-term self-renewal of mouse iPSCs for up to 17 passages without GSK3beta (CHIR99021) and Erk (PD0325901) inhibitors. Overall, our engineered ECM protein, which is cost-effective to produce in prokaryotic origin and flexible to modify with other cell adhesion peptides or growth factors, provides a novel approach for expansion of mouse iPSCs in vitro. PMID- 27269812 TI - A Platform to Enable the Pharmacological Profiling of Small Molecules in Gel Based Electrophoretic Mobility Shift Assays. AB - We describe a polyacrylamide gel casting cassette that overcomes limitations of commercially available gel electrophoresis equipment. This apparatus molds a single polyacrylamide gel that can evaluate more than 200 samples in parallel, is loaded with a multichannel pipettor, and is flexible with respect to composition of the separating matrix. We demonstrate its use to characterize inhibitors of enzymes that modify protein and nucleic acid substrates. Throughputs of greater than 1000 samples per day were achieved when this system was paired with a quantitative laser-based imaging system, yielding data of remarkable quality. PMID- 27269813 TI - The role of rational and experiential processing in influencing the framing effect. AB - Research on individual differences and the framing effect has focused primarily on how variability in rational processing influences choice. However, we propose that measuring only rational processing presents an incomplete picture of how participants are responding to framed options, as orthogonal individual differences in experiential processing might be relevant. In two studies, we utilize the Rational Experiential Inventory, which captures individual differences in rational and experiential processing, to investigate how both processing types influence decisions. Our results show that differences in experiential processing, but not rational processing, moderated the effect of frame on choice. We suggest that future research should more closely examine the influence of experiential processing on making decisions, to gain a broader understanding of the conditions that contribute to the framing effect. PMID- 27269814 TI - "Uberizing" home care in Ontario. AB - This article looks at home care in Ontario and its role as a foundation for a sustainable healthcare system in the future. Beginning with the history and evolution of the service delivery model, it examines current challenges and opportunities to unleash the potential of home care within a more integrated model for patient-centred care for the future. An in-depth look at how to better coordinate, integrate, and fund care for patients is highlighted. PMID- 27269815 TI - "We Should Talk"-Moving knowledge into action by learning to engage patients, families, and healthcare staff to communicate for patient safety. AB - Innovation in patient engagement and empowerment has been identified as a priority area in the Canadian healthcare system. This article describes the development and implementation of the We Should Talk campaign at an academic pediatric hospital. Through the use of a guiding theoretical framework and a multidisciplinary project team, a multimedia campaign was designed to inspire staff, patients and families to effectively communicate to improve patient safety. The We Should Talk campaign provides a case study for how an organization can foster frontline improvement through the engagement of patient, families, and healthcare providers. PMID- 27269816 TI - Contrast-enhanced ultrasound-guided percutaneous microwave ablation of renal cell carcinoma that is inconspicuous on conventional ultrasound. AB - PURPOSE: This study was designed to determine the safety, effectiveness and feasibility of contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma (RCC) that is inconspicuous on conventional ultrasound (US). MATERIALS AND METHODS: A total of 32 RCC nodules in 29 patients (23 men and 6 women) were treated with CEUS-guided percutaneous MWA between January 2010 and September 2014. The median maximum diameter of the nodules was 2.4 cm (interquartile range: 1.8-2.9 cm). The US contrast agent was SonoVue, a second-generation contrast agent. CEUS was applied before the needle was inserted into the tumour, and percutaneous MWA was performed under CEUS guidance. RESULTS: In total 31 tumours were successfully visualised via CEUS using 1-2 (1.0-2.0 mL) contrast agent injections, and percutaneous MWA was performed under CEUS-guidance. The technical success rate of CEUS-guided percutaneous MWA of RCC was 96.9% (31/32). The mean number of sessions of CEUS guided percutaneous MWA for each tumour was 1.2 +/- 0.4. The mean duration of energy application for each tumour was 7.3 +/- 2.7 min. All patients were followed up for 3-71 months (median 17 months) to observe the therapeutic effects and complications. The therapeutic effects were assessed at follow-up with computed tomography (CT) or magnetic resonance imaging (MRI) and CEUS. There was no local tumour progression and the technique effectiveness rate was 100% (31/31). The complications rate was 6.5% and the major complications rate was 3.2%. We observed one case of pleural effusion and one case of renal subcapsular haemorrhage after the percutaneous MWA procedures. CONCLUSION: CEUS-guided percutaneous MWA is a safe, efficient and feasible therapy for patients with RCCs inconspicuous on conventional US. PMID- 27269817 TI - Need for Specialized Support Services for Nurse Victims of Physical Assault by Psychiatric Patients. AB - Assault of nurses in the psychiatric setting is an ongoing global concern. In a prior study by these authors, many nurses reported concern about the lack of supportive interventions offered to nurses after the assault event. These nurses reported ongoing psychosocial and emotional disturbance consistent with symptoms of post-traumatic stress disorder. A follow-up study was done to investigate the perceived need of assaulted nurses for specialized support groups to assist them in dealing with the experience. A quantitative, cross sectional survey descriptive research design was done to assess assaulted nurses' perceived need for specialized support groups. The survey also gathered data relating to the reporting of the assault. A qualitative narrative section was added to gather data that might have been missed in the quantitative segment. The sample consisted of 57 previously assaulted nurses currently working at multiple acute care sites. Study findings showed that if specialized support groups were available, 57% of the nurses might be interested in attending these, and 41% would be interested in attending these. These nurses also reported multiple signs and symptoms of post-traumatic stress disorder. Considering the serious negative impact of assault on nurses and their desire for follow-up support, there is a need for the availability of supportive services. PMID- 27269818 TI - Developing and implementing a social prescribing initiative in primary care: insights into the possibility of normalisation and sustainability from a UK case study. AB - : Aim To conduct a process-based evaluation of the inception and early implementation of a social prescribing initiative (Healthy Connections Stewartry) in two UK General Practices. BACKGROUND: Prescribing a range of social, cultural, arts and educational activities to clients in primary care (known as 'social prescribing' or 'community linking schemes') as a means of addressing long-term physical health conditions and promoting mental health and well-being is becoming increasingly prominent and popular. However, concerns exist over a lack of evidence of effectiveness and formalised insights into how such initiatives may be optimally implemented. METHODS: Within a case study design and using 1-1 semi structured interviews, three related data sets were developed over a 12-month period from 30 purposively sampled informants: the project steering group; the wider primary care team; and various community groups. Data analysis drew on various theoretical resources, particularly those pertaining to nurturing sufficient capacity for the organisational 'normalisation' of this practice and understanding the dynamic flows and linkages between potential clients, 'prescribing' primary care staff and the available community resources. Findings The inception and implementation of the initiative had been broadly successful and that more generally, there were grounds to suggest that these practices were becoming 'normalised' into the day-to-day cultures and routines of the primary care organisations. A series of procedural features are considered significant in achieving such ends. Some specific barriers to change are identified and ultimately in the context of potential 'transferability', a wider reflection is undertaken of the potential for such innovative practice to become established in less advantageous organisational circumstances. Fundamental difficulties are recognised and thus the need for formally implemented 'change' processes. Furthermore, for social prescribing to become a pervasive feature of health-care provision, the need for necessary capacity and resources is stressed. PMID- 27269820 TI - Visible Light Photoredox-Catalyzed O-Sialylation Using Thiosialoside Donors. AB - An efficient protocol for the O-sialylation using thiosialoside donors under visible light photocatalysis was developed. Thiosialosides were activated under the irradiation with blue light in the presence of Ru(bpy)3(PF6)2 as photocatalyst, Umemoto's reagent as CF3 radical source and Cu(OTf)2 as an additive in acetonitrile/dichloromethane at -30 degrees C, and the subsequent reaction with glycosyl acceptors generally produced the desired sialosides in good to excellent yields with the satisfactory alpha-selectivity. PMID- 27269819 TI - Hepatitis C virus antibody titers associated with cognitive dysfunction in an asymptomatic community-based sample. AB - BACKGROUND: Hepatitis C virus (HCV) infection is associated with cognitive dysfunction in clinic-based studies. The risk could be attributed to factors such as antiviral medications, substance abuse, or coincidental infection. AIM: The aim was to evaluate cognitive function in relation to HCV antibody titers in a community-based sample of asymptomatic individuals at low risk for substance abuse. METHOD: Adults were ascertained from a community in Mansoura, Egypt, where HCV is endemic (n = 258). Cognitive performance was evaluated using the Arabic version of the Penn Computerized Neurocognitive Battery. Substance abuse and psychopathology were also assessed. Antibodies to HCV and Toxoplasma gondii (TOX), a common protozoan that can affect cognition, were estimated using serological IgG assays. RESULTS: The prevalence of HCV and TOX infection was 17.6% and 52.9%, respectively. HCV antibody titers were significantly associated with worse function in four cognitive tests for accuracy and three tests for speed, after adjusting for covariates (p < .05, beta coefficients, 2.1-3.2). TOX antibody titers were associated with impaired accuracy in one test. CONCLUSIONS: The association between HCV antibody titers and cognitive impairment is not mediated by antiviral treatment or substance abuse in this sample. Whether HCV has a causal role in the cognitive dysfunction should be investigated. PMID- 27269821 TI - Mimicking Form and Function of Native Small Diameter Vascular Conduits Using Mulberry and Non-mulberry Patterned Silk Films. AB - Autologous graft replacement as a strategy to treat diseased peripheral small diameter (<=6 mm) blood vessel is often challenged by prior vein harvesting. To address this issue, we fabricated native-tissue mimicking multilayered small diameter vascular graft (SDVG) using mulberry (Bombyx mori) and Indian endemic non-mulberry (Antheraea assama and Philosamia ricini) silk. Patterned silk films were fabricated on microgrooved PDMS mold, casted by soft lithography. The biodegradable patterned film templates with aligned cell sheets were rolled onto an inert mandrel to mimic vascular conduit. The hemocompatible and mechanically strong non-mulberry films with RGD motif supported ~1.2 folds greater proliferation of vascular cells with aligned anchorage. Elicitation of minimal immune response on subcutaneous implantation of the films in mice was complemented by ~45% lower TNF alpha secretion by in vitro macrophage culture post 7 days. Pattern-induced alignment favored the functional contractile phenotype of smooth muscle cells (SMCs), expressing the signature markers calponin, alpha-smooth muscle actin (alpha-SMA), and smooth muscle myosin heavy chain (SM-MHC). Endothelial cells (ECs) exhibited a typical punctuated pattern of von Willebrand factor (vWF). Deposition of collagen and elastin by the SMCs substantiated the aptness of the graft with desired biomechanical attributes. Furthermore, the burst strength of the fabricated conduit was in the range of ~915-1260 mmHg, a prerequisite to withstand physiological pressure. This novel fabrication approach may eliminate the need of maturation in a pulsatile bioreactor for obtaining functional cellular phenotype. This work is thereby an attestation to the immense prospects of exploring non-mulberry silk for bioengineering a multilayered vascular conduit similar to a native vessel in "form and function", befitting for in vivo transplantation. PMID- 27269867 TI - Anxiety disorders in breast cancer: Prevalence, types, and determinants. AB - The coexistence of anxiety disorders among women with breast cancer has been linked with delay in diagnosis, treatment abandonment, and poor quality of life. This study investigated anxiety disorders with their determinants among 200 participants with histological diagnosis of breast cancer. A questionnaire was designed to elicit sociodemographic and clinical factors, while the schedule for clinical assessment in neuropsychiatry (SCAN) was used to ascertain the presence of anxiety disorders. The mean age of participants was 49.6 years (SD = 11.2) and more than half (54%) presented with advanced cancers (stages 3 and 4). Anxiety disorder was observed in 38 (19%) of the participants. Low income, absence of previous history of breast cancer, and early stage of breast cancer were the significant determinants of anxiety disorders (p < 0.05). However, only absence of previous history of breast cancer (odds ratio [OR] = 3.460, 95% confidence interval [CI] = 1.200-6.960) and early stage of breast cancer (OR = 1.560, 95% CI = 1.120-2.174) were the determinants of anxiety disorders following logistic regression. We advocate for public awareness to promote early screening. Similarly, there is need to improve access to care and integrate culturally appropriate psychosocial intervention into breast cancer care using the available knowledge on vulnerability factors. Further study on anxiety disorders in breast cancer is indicated. PMID- 27269868 TI - Graphene Meets Microbubbles: A Superior Contrast Agent for Photoacoustic Imaging. AB - Coupling graphene with a soft polymer surface offers the possibility to build hybrid constructs with new electrical, optical, and mechanical properties. However, the low reactivity of graphene is a hurdle in the synthesis of such systems which is often bypassed by oxidizing its carbon planar structure. However, the defects introduced with this process jeopardize the properties of graphene. In this paper we present a different approach, applicable to many different polymer surfaces, which uses surfactant assisted ultrasonication to exfoliate, and simultaneously suspend, graphene in water in its intact form. Tethering pristine graphene sheets to the surfaces is accomplished by using suitable reactive functional groups of the surfactant scaffold. We focused on applying this approach to the fabrication of a hybrid system, made of pristine graphene tethered to poly(vinyl alcohol) based microbubbles (PVA MBs), designed for enhancing photoacoustic signals. Photoacoustic imaging (PAI) is a powerful preclinical diagnostic tool which provides real time images at a resolution of 40 MUm. The leap toward clinical imaging has so far been hindered by the limited tissues penetration of near-infrared (NIR) pulsed laser radiation. Many academic and industrial research laboratories have met this challenge by designing devices, each with pros and cons, to enhance the photoacoustic (PA) signal. The major advantages of the hybrid graphene/PVA MBs construct, however, are (i) the preservation of graphene properties, (ii) biocompatibility, a consequence of the robust anchoring of pristine graphene to the bioinert surface of the PVA bubble, and (iii) a very good enhancement in a NIR spectral region of the PA signal, which does not overlap with the signals of PA active endogenous molecules such as hemoglobin. PMID- 27269866 TI - 6beta-N-Heterocyclic Substituted Naltrexamine Derivative BNAP: A Peripherally Selective Mixed MOR/KOR Ligand. AB - The 6beta-N-heterocyclic naltrexamine derivative, NAP, has been demonstrated to be a peripherally selective mu opioid receptor modulator. To further improve peripheral selectivity of this highly potent ligand, its pyridal ring was quaterinized with benzyl bromide to produce BNAP. In radioligand binding assay, the Ki of BNAP for MOR was 0.76 +/- 0.09 nM and was >900-fold more selective for MOR than DOR. The Ki for KOR was 3.46 +/- 0.05 nM. In [(35)S]GTPgammaS ligand stimulated assay, BNAP showed low agonist efficacy with 14.6% of the maximum response of DAMGO with an EC50 of 4.84 +/- 0.6 nM. However, unlike its parent compound NAP, BNAP displayed partial agonist activity at KOR with % maximum response at 45.9 +/- 1.7% of U50,488H. BNAP did not reverse morphine-induced antinociception when administered subcutaneously but did antagonize when administered intracerebroventricularly. BNAP antagonized morphine-induced contractions of the circular muscle in mice colon. BNAP inhibition of field stimulated contractions in longitudinal muscle strips for the guinea-pig ileum were also blocked by nor-BNI, a kappa opioid receptor antagonist. BNAP induced inhibition of acetic acid induced abdominal stretching in chronic morphine treated mice. These findings suggest that BNAP is a dual MOR antagonist/KOR agonist and may have functional use in irritable bowel patients. PMID- 27269879 TI - Release of levetiracetam from extended-release tablets that appear intact in patient stool. PMID- 27269869 TI - Alcohol intake alters immune responses and promotes CNS viral persistence in mice. AB - Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. PMID- 27269880 TI - Cholesterol induces proliferation of chicken primordial germ cells. AB - Primordial germ cells (PGCs) are the precursors of sperm and eggs and may serve as suitable cells for use in research in developmental biology and transgenic animals. However, the long-term propagation of PGCs in vitro has so far been plagued by the loss of their germ cell characteristics. This is largely because of the scarcity of knowledge concerning cell division and proliferation in these cells and the poor optimization of the culture medium. The sonic hedgehog (SHH) signaling pathway is involved in proliferation of many types of cells, but little is known about its role in chicken PGCs. The results of the current study indicate that the proliferation of chicken PGCs increases significantly when cholesterol, a molecule that facilitates the trafficking of HH ligands, is supplemented in the culture medium. This effect was attenuated when an SHH antagonist, cyclopamine was added, suggesting the involvement of SHH signaling in this process. The characterization of PGCs treated with cholesterol has shown that these cells express germ-cell-related markers and retain their capability to colonize the embryonic gonad after re-introduction to vasculature of stage-15 HH embryos, indicating that proliferation of PGCs induced by cholesterol does not alter the germ cell characteristics of these cells. PMID- 27269881 TI - Distribution of hypothalamic vasoactive intestinal peptide immunoreactive neurons in the male native Thai chicken. AB - Avian prolactin (PRL) secretion is under stimulatory control by the PRL-releasing factor (PRF), vasoactive intestinal peptide (VIP). The neuroendocrine regulation of the avian reproductive system has been extensively studied in females. However, there are limited data in males. The aim of this study was to elucidate the VIPergic system and its relationship to PRL and testosterone (T) in the male native Thai chicken. The distributions of VIP-immunoreactive (-ir) neurons and fibers were determined by immunohistochemistry. Changes in VIP-ir neurons within the nucleus inferioris hypothalami (IH) and nucleus infundibuli hypothalami (IN) areas were compared across the reproductive stages. Plasma levels of PRL and T were determined by enzyme-linked immunosorbent assay and then compared across the reproductive stages. The results revealed that the highest accumulations of VIP ir neurons were concentrated only within the IH-IN, and VIP-ir neurons were not detected within other hypothalamic nuclei. Within the IH-IN, VIP-ir neurons were low in premature and aging males and markedly increased in mature males. Changes in VIP-ir neurons within the IH-IN were directly mirrored with changes in PRL and T levels across the reproductive stages. These results suggested that VIP neurons in the IH-IN play a regulatory role in year-round reproductive activity in males. The present study also provides additional evidence that VIP is the PRF in non seasonal, continuously breeding equatorial species. PMID- 27269882 TI - Impact of chronic kidney disease on patients with unprotected left main coronary artery disease treated with coronary artery bypass grafting or drug-eluting stents. AB - OBJECTIVES: This study aimed to evaluate clinical outcomes after percutaneous coronary intervention with drug-eluting stents (DESs) or coronary artery bypass grafting (CABG) in unprotected left main coronary artery (ULMCA) disease patients with and without chronic kidney disease. BACKGROUND: The optimal coronary revascularization strategy for ULMCA disease patients with chronic kidney disease remains uncertain. METHODS: The sample included 818 ULMCA disease patients who received DESs (n=358) or underwent CABG (n=460). We retrospectively compared clinical parameters and outcomes between different endogenous creatinine clearance rates [estimated glomerular filtration rates (eGFRs), ml/min*1.73 m]. RESULTS: The incidences of major adverse cardiocerebral events, all-cause death, cardiac death, and stroke were not significantly different between the DES and the CABG groups. The DES group had significantly higher risks of myocardial infarction (MI) and target vessel revascularization than the CABG group. Compared with the CABG group, the hazard ratios for target vessel revascularization were 3.965 [95% confidence interval (CI): 1.743-9.023, P=0.001] in the eGFR of at least 60 group and 46.463 (95% CI: 4.558-473.639, P=0.001) in the eGFR 45-59 group. The rate of MI was higher in patients treated with DESs in the eGFR of less than 45 group (hazard ratio: 14.098, 95% CI: 1.123-176.988, P=0.040). CONCLUSION: For patients with ULMCA disease at risk of higher repeat revascularization with normal renal function or eGFR of at least 45 ml/min*1.73 m, DESs are a safe alternative to CABG. However, for patients with severely reduced kidney function (eGFR<45 ml/min*1.73 m), DESs should be selected after careful evaluation of MI risk. PMID- 27269883 TI - Parent-reported symptoms, impairment, helpfulness of treatment, and unmet service needs in a follow-up of outpatient children with attention-deficit/hyperactivity disorder. AB - BACKGROUND: Limited information exists regarding the associations between impairment, symptoms, helpfulness of treatments, and service needs after initial treatment of children with attention-deficit/hyperactivity disorder (ADHD). AIMS: The aims of this study were to examine persistence rates and associations between parent-reported symptoms, impairment, helpfulness of treatments, and service needs in a retrospective follow-up study of children with ADHD. METHODS: Parents of 214 children with a mean age of 12.6 years (SD = 2.1) who were diagnosed with ADHD at five child and adolescent mental health clinics (CAMHS) completed questionnaires 1-10 years (mean = 3.7 years, SD = 2.2) after baseline assessment. The response rate was 43.4%. A community comparison group (n = 110) was recruited from the same area. RESULTS: Approximately two-thirds (60.3%) of the sample fulfilled the DSM-IV symptom criteria of ADHD at follow-up, 84.3% were functionally impaired, and most children (84.7%) were on medication. Inattentive and emotional symptoms were the strongest predictors of impairment across impairment areas. Perceived helpfulness of different treatments varied from 71.8 88.7%, and no significant difference was found between the ADHD sub-groups regarding reported helpfulness. 'Adjustment of the school situation' was the most frequent service need, and approximately half of the parents reported needs for care co-ordination. Children fulfilling the symptom criteria of the ADHD Combined sub-group were most impaired and had most service needs. CONCLUSIONS: At follow up, children were highly symptomatic and impaired, despite a high rate of persistent medication treatment. The findings underline the need for more tailored treatment and co-ordinated care over time. PMID- 27269885 TI - Effect of "heat shock" treatments on QPX disease and stress response in the hard clam, Mercenaria mercenaria. AB - The hard clam, Mercenaria mercenaria, is one of the most valuable commercial mollusk species along the eastern coast of the United States. Throughout the past 2 decades, the hard clam industry in the Northeast was significantly impacted by disease outbreaks caused by a lethal protistan parasite known as Quahog Parasite Unknown (QPX). QPX is an opportunistic pathogen and the infection has been shown to be a cold water disease, where warmer conditions (above 21 degrees C) lead to disease reduction and clam healing. In vitro studies also showed a sharp reduction in parasite growth and survivorship at temperatures exceeding 27 degrees C. In this study, we evaluated the effect of short-term exposures to high temperatures on QPX disease dynamic and clam recovery. Infected clams were collected from an enzootic site and subsequently submitted to one of ten "heat shock" treatments involving a gradient of temperatures and exposure times. QPX prevalence was compared before and 10weeks after heat shock to assess the effect of each treatment on disease progress. Expression of several stress-related genes was measured 1 and 7days after heat shock using qPCR to evaluate the effect of each treatment on clam physiology. Anti-QPX activity in clam plasma was also measured in an attempt to link changes in defense factors to thermal stress and disease progress. Our results suggest that brief exposures to moderate high temperatures promote the greatest remission while imposing the mildest stress to clams. These results are discussed with the aim of providing the industry with possible strategies to mitigate QPX disease. PMID- 27269884 TI - Skin microbiota is the main reservoir of Roseomonas mucosa, an emerging opportunistic pathogen so far assumed to be environmental. AB - Roseomonas spp. are increasingly involved in human infectious diseases. The environmental source for infection is generally admitted in published cases owing to the origin of most Roseomonas species and to their affiliation to the family Acetobacteraceae in Rhodospirillales, which mainly groups environmental bacteria. For a better delineation of Roseomonas habitat and infectious reservoir, we related phenotype, phylotype (16S rRNA gene), genomotype (pulsed-field gel electrophoresis) and origin of 33 strains isolated from humans, hospital environment and natural environment. Genetic and metagenomic databases were also surveyed. The population structure of the genus showed clades associated with humans, whereas others grouped environmental strains only. Roseomonas mucosa is the main human-associated species and the study supported the idea that opportunistic infections due to this species are related to the patient skin microbiota rather than to the environment. In contrast, some strains belonging to other species isolated from patients with cystic fibrosis were related to environmental clades, suggesting an exogenous source for patient colonization. Accurate knowledge about the reservoirs of opportunistic pathogens that have long been considered of environmental origin is still needed and would be helpful to improve infection control and epidemiological survey of emerging human pathogens. PMID- 27269886 TI - Treatment of warts and molluscum: what does the evidence show? AB - PURPOSE OF REVIEW: Warts and molluscum contagiosum are very common viral skin infections, usually presenting in childhood. Despite the large number of people affected by them, high-quality trials of treatment are few and treatment is often chosen on the basis of cost, convenience and tradition. RECENT FINDINGS: Over recent years, two further trials of the most commonly used treatments for warts, salicylic acid and cryotherapy, have been performed and for molluscum contagiosum, there is growing evidence for the use of irritants. For both infections, there are new evaluations of immunological approaches to therapy. SUMMARY: Strong, high-quality evidence for treatments used very frequently for warts or molluscum is still lacking, but recent publications have helped to strengthen or weaken belief in commonly used therapies and to add weight to the immunological approach to management. PMID- 27269888 TI - Prevalence and health care seeking behaviour for sexually transmitted infections among in-school adolescents in Ado-Ekiti, South-Western Nigeria. AB - BACKGROUND: In Nigeria, adolescents are highly vulnerable to sexually transmitted infections (STIs) which have the potential of jeopardising their future reproductive lives if poorly treated. OBJECTIVE: To determine the prevalence and health care seeking behaviour for STIs among secondary school adolescents in Ado, South-Western Nigeria. SUBJECTS: Male and female adolescents aged 10-19 years. METHODS: The study employed a descriptive cross-sectional design. A pre-tested, self-administered, semi-structured questionnaire was used to elicit information from 560 adolescents selected from public and private secondary schools in Ado Local Government Area (LGA) of Ekiti State, using a multistage sampling technique. The data were analyzed using descriptive and inferential statistics. Analyzed data were presented in the form of tables and charts. RESULTS: Two hundred and fifty-one (47.1%) respondents had previous symptoms of STIs. The commonest symptoms among the males were penile discharge (30.5%), painful micturition (30.5%) and stomach pain with swollen testes (25.4%). The commonest symptoms among the females were genital itching (27.6%), genital sores (14.1%) and painful micturition (13.1%). Only 26.7% sought treatment from a health facility; 37.0% did nothing; 15.9% went to patent medicine stores, 10.0% used herbs; the rest did self-medication or prayed. CONCLUSION: The prevalence of STI symptoms among adolescents in Ado-Ekiti is high but their health care seeking behaviour is poor. Health education about the dangers of untreated STI and the importance of seeking treatment early, targeted at adolescents, should be intensified. PMID- 27269887 TI - IL-17A synergistically stimulates TNF-alpha-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation. AB - BACKGROUND: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. MATERIALS AND METHODS: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) alpha on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF kappaB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol. RESULTS: IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-alpha showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1beta and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-alpha and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-alpha-induced IL-8 production. CONCLUSIONS: IL-17A in the combination with TNF-alpha or IL-1beta showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells. PMID- 27269889 TI - Long-term positive and negative psychosocial outcomes in young childhood cancer survivors, type 1 diabetics and their healthy peers. AB - OBJECTIVE: This study examined posttraumatic growth (PTG) in young childhood cancer survivors (CCS) and type 1 diabetics (DM), with physically healthy peers as the control group (CG). Anxiety and depression as negative mental outcomes in the three groups, as well as fear of progression in DM and CCS were examined. METHODS: A total of 107 participants with ages ranging from 18 to 35 years were examined: CCS (n=33), type 1 diabetics (n=39) and peers without a history of chronic disease (n=35). PTG and negative psychosocial outcomes were assessed with self-report questionnaires. RESULTS: There was a significant difference between the groups regarding PTG. On a subscale level DM reported higher appreciation of life (p=0.024), higher personal strength (p=0.010), and more new possibilities (p=0.010) compared to CG. CCS experienced higher spiritual changes than DM (p=0.050). DM reported higher levels of anxiety compared to CCS (p=0.026) and CG (p=0.049). Depression was higher in DM compared to CG (p=0.003). Fear of progression was higher in DM compared to CCS (p<0.001). CONCLUSION: These findings show that psychological growth was experienced by young CCS and participants with DM. Furthermore, these findings highlight that adolescents with a significant health diagnosis in childhood or youth can undergo a similar or even more positive psychosocial development as peers without a history of chronic disease. However, young type 1 diabetics seem to be a more vulnerable group in terms of anxiety, depression and fear of progression. PMID- 27269890 TI - Both high and low testosterone levels may play a role in suicidal behavior in adolescent, young, middle-age, and older men: a hypothesis. AB - Many studies suggest that testosterone plays a role in the regulation of mood and behavior. Most but not all investigations of the relationship between testosterone and suicidality found relations between testosterone and suicidal behavior. The balance of evidence is in favor of the view that testosterone is involved in the pathophysiology of suicidality. The author has previously proposed that suicidal behavior in adolescents and young adults is associated with high testosterone levels, whereas suicidality in older men is associated with decreased testosterone levels. However, both high and low testosterone levels can be observed in adolescent, young, middle-aged and older men. In this article, the author proposes that both high and low testosterone levels may play a role in suicidal behavior in men of any age. PMID- 27269892 TI - GCK mutations in Chinese MODY2 patients: a family pedigree report and review of Chinese literature. AB - BACKGROUND: Maturity-onset diabetes of the young type 2 (MODY2) is caused by mutations in the glucokinase (GCK) gene and is rare in the Chinese population. We report three Chinese families with MODY2 and the sequencing of the GCK gene. METHODS: Three unrelated Chinese families with MODY2 and their pedigrees were investigated. In Family 1, the proband was a 7-year-old girl with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Her mother and maternal grandfather had IFG. In Family 2, the proband was a boy who had diabetes mellitus at 11 years. His sister had IFG. His father and grandmother had diabetes mellitus at 22 and 25 years, respectively. In Family 3, the proband was a boy who had IFG and IGT at 12 years. His sister had diabetes mellitus at 8 years. His father and grandfather had IFG and/or IGT. The GCK gene was directly sequenced. RESULTS: Diabetes mellitus or IFG/IGT was found among three consecutive generations in three families. One novel nonsense heterozygous mutation in exon 5 (c.556 C>T, p.Arg 186 stop) was detected in Family 1. Another novel frameshift mutation in exon 4 (c.367-374dupTTCGACTA, p.Ile 126 fs) was found in Family 2. A previously reported, a missense heterozygous mutation in exon 5 (c.571 C>T, p.Arg 191Trp) was detected in Family 3. CONCLUSIONS: The thorough investigation of three Chinese families with MODY2 revealed two novel mutations and one known mutation. GCK gene sequencing helps in MODY2, especially when there is uncertain IFG or IGT. PMID- 27269891 TI - Cystinosis in Eastern Turkey. AB - BACKGROUND: This study was conducted to investigate CTNS (cystinosin, lysosomal cystine transporter) gene mutations and the clinical spectrum of nephropathic cystinosis among patients diagnosed with the disease in a single center in Turkey. METHODS: Patients' clinical and laboratory data were extracted from an electronic health registry. Molecular CTNS gene analysis was performed using either next-generation sequencing or Sanger sequencing. RESULTS: Eleven patients (age range: 1.5-12 years) from nine families were identified. The presenting complaint was growth retardation in seven patients; polydipsia and polyuria in three patients; and vomiting in two patients. At presentation, electrolyte loss was noted in all patients, of which eight patients presented with metabolic acidosis, and three patients presented with metabolic alkalosis. All patients also presented with proteinuria and glucosuria, and four patients developed varying degrees of renal insufficiency, for which peritoneal dialysis was initiated in one patient. Cystine crystals were detected via ocular examination in one patient at presentation. No cystine crystals were detected among patients who underwent bone marrow aspiration. In the CTNS gene, a p.T7FX7 (c.18-21del4bp) mutation was detected in three patients, whereas a p.E227E (c.681 G>A) (homozygous) mutation was detected in eight patients. CONCLUSIONS: We detected two distinct mutations, p.T7FX7 (c.18-21del4bp) and p.E227E (c.681 G>A) (homozygous), in the CTNS gene in 11 patients with cystinosis from the East Anatolian region of Turkey. Patients with a homozygous c.681 G>A (p.E227E) mutation are more likely to develop chronic renal failure and should be monitored closely, whereas patients with a p.T7FX7 (c.18-21del4bp) mutation have a milder phenotype. Additionally, metabolic alkalosis does not exclude cystinosis, although cystinosis is a cause of proximal renal tubular acidosis. PMID- 27269893 TI - Ghrelin, insulin-like growth factor I and adipocytokines concentrations in born small for gestational age prepubertal children after the catch-up growth. AB - BACKGROUND: In children born small for gestational age (SGA) with catch-up growth, a higher risk of insulin resistance (IR) and cardiovascular diseases is noted. Ghrelin stimulates a growth hormone (GH) secretion and regulates lipid and carbohydrate metabolism. We assessed gherlin's influence on achieving normal height and the occurrence of metabolic complications in SGA children. METHODS: Ghrelin, insulin-like growth factor type I (IGF-I), leptin, adiponectin, resistin, glucose, insulin and lipid concentrations were analysed in 134 prepubertal children in four groups: normal-height SGA, short SGA, normal-height born appropriate for gestational age (AGA) and short AGA. RESULTS: Ghrelin and IGF-I concentrations were significantly higher while adiponectin - lower in normal-height SGA comparing to others. CONCLUSIONS: The increased production of ghrelin and IGF-I seems to be an adaptive mechanism to achieve normal growth in SGA children. The significance of high ghrelin and low adiponectin concentrations, observed in normal-height prepubertal SGA children, requires elucidation, with reference to the development of metabolic complications. PMID- 27269895 TI - Pseudohyperkalemia due to severe leukocytosis: case presentation. PMID- 27269894 TI - Orofacial antinociceptive effect of the ethanolic extract of Annona vepretorum Mart. (Annonaceae). AB - Annona vepretorum Mart. (Annonaceae) is a species popularly known in Brazil as "araticum" and "pinha da Caatinga". We have evaluated the antinociceptive effects of A. vepretorum in formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice. Male Swiss mice were pretreated with either saline (p.o.), A. vepretorum ethanol extract (Av-EtOH 25, 50 and 100 mg/kg, p.o.), or morphine (10 mg/kg, i.p.), before formalin, capsaicin, or glutamate was injected into the right upper lip. Pre-treatment with Av-EtOH at all doses produced a reduction in face-rubbing behavior induced by formalin in both phases, and these pre treatments also produced a significant antinociceptive effect in the capsaicin and glutamate tests. Pre-treatment with naloxone (1.5 mg/kg, i.p.) did not reverse the antinociceptive activity of the extract at the dose of 100 mg/kg in the first phase of this test. Our results suggest that Av-EtOH might be useful in the treatment of orofacial pain. PMID- 27269896 TI - The evolution of genomic stability to a mechanism in reproduction and psychiatry. AB - There are two forms of immune defense, the specific or adaptive immune defense and the unspecific innate immune defense. Vaccination is utilized against specific bacteria via the adaptive immune system. The innate immunity DNA stress defense is a non-toxic mechanism developed in yeasts and conserved in mammals and in plants. Although the steroidal hormone cascade has overtaken the stress response and allows superfast response via non-genomic receptors, the old innate immunity response is still mediated via the steroidal hormones cascade. The classical drug/receptor model has provided for many solutions, however, in antibiotics, cancer, and in severe mental diseases this model reaches to certain limits. The NIH/Department of Mental Health has developed a new model that shows severe mental diseases may be immune diseases that can be treated by replacing old diseased nerve cells by new healthy nerve cells, where the old innate immunity may be exploited. This means that severe mental diseases are physical diseases. A newly developed model, where modifications of the steroidal hormone cascade help to understand bipolarity, schizophrenia, and PTSD in men and women can be transferred to gynecological hormone modifications in women, where innate immunity is mediated via the same steroidal hormone cascade. Treatment via immune response via the DNA cascade should be developed in cancer, infections and severe mental disease, because foreign cells or diseased cells may be removed by the unspecific innate immunity. PMID- 27269897 TI - LandScape: a simple method to aggregate p-values and other stochastic variables without a priori grouping. AB - In many areas of science it is custom to perform many, potentially millions, of tests simultaneously. To gain statistical power it is common to group tests based on a priori criteria such as predefined regions or by sliding windows. However, it is not straightforward to choose grouping criteria and the results might depend on the chosen criteria. Methods that summarize, or aggregate, test statistics or p-values, without relying on a priori criteria, are therefore desirable. We present a simple method to aggregate a sequence of stochastic variables, such as test statistics or p-values, into fewer variables without assuming a priori defined groups. We provide different ways to evaluate the significance of the aggregated variables based on theoretical considerations and resampling techniques, and show that under certain assumptions the FWER is controlled in the strong sense. Validity of the method was demonstrated using simulations and real data analyses. Our method may be a useful supplement to standard procedures relying on evaluation of test statistics individually. Moreover, by being agnostic and not relying on predefined selected regions, it might be a practical alternative to conventionally used methods of aggregation of p-values over regions. The method is implemented in Python and freely available online (through GitHub, see the Supplementary information). PMID- 27269898 TI - The integration and interpretation of pharmacogenomics - a comparative study between the United States of America and Europe: towards better health care. AB - The study of pharmacogenomics has, by harnessing sequence information from human genomes, the potential to lead to novel approaches in drug discovery, an individualized application of drug therapy, and new insights into disease prevention. For this potential to be realized results need to be interpreted to the prescriber into a format which dictates an action. This mini review briefly describes the history, the regulatory environment, opinions towards, and implementation, integration and interpretation of pharmacogenomics in the United States of America and Europe. The article discusses also how interpretation of pharmacogenomics could move forward to better implementation in health care. PMID- 27269899 TI - A Call for Synthesis of Water Research to Achieve the Sustainable Development Goals by 2030. PMID- 27269900 TI - Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study. PMID- 27269901 TI - Report: impact of inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), 2 conditions characterized by chronic inflammation. Approximately 1.17 million people in the United States are affected by these 2 conditions. It is theorized that a genetic susceptibility coupled with environmental factors, such as smoking, antibiotics, oral contraceptives, appendectomy, or diet, may influence the development of IBD. Patients with UC and CD may exhibit similar symptoms, and the conditions are often misclassified, as there is a lack of standard criteria for diagnosing IBD. Therefore, it is important for clinicians to rule out any diarrhea-related conditions for an accurate diagnosis. UC and CD typically manifest in early adulthood, and the chronic nature of these conditions greatly impacts a patient's perception, body image, and quality of life. The inability to participate in social activities due to UC and CD impacts not only patients, but also those with whom they have close relationships. PMID- 27269902 TI - Report: pharmacotherapy for moderate to severe inflammatory bowel disease: evolving strategies. AB - Moderate to severe disease causes substantial morbidity in inflammatory bowel disease (IBD). The approach to pharmacotherapy for patients with moderate to severe ulcerative colitis and Crohn's disease is undergoing a fundamental transformation to change the course of disease in these patients. Disease severity is being redefined to consider the impact on the patient, its inflammatory burden, and the disease course. Prevention of disease progression and complications are replacing symptomatic remission as the goal of therapy. To achieve these goals, the treatment approach is evolving from a stepwise to a treat-to-target approach, with patients stratified to treatment according to their risk of disease progression or complications. The primary drug classes for induction and maintenance of remission in moderate to severe IBD are corticosteroids, thiopurines, tumor necrosis factor antagonists, and vedolizumab. Use of these drug classes is changing as IBD management evolves. This article reviews the efficacy, adverse effects, drug interactions, and special issues for each class. The role for each class is formulated based on results of key clinical trials and meta-analyses, as well as clinical practice guideline recommendations. PMID- 27269904 TI - Environmental Nanotoxicology. PMID- 27269903 TI - Report: economic implications of inflammatory bowel disease and its management. AB - Crohn's disease and ulcerative colitis, the 2 most common inflammatory bowel diseases (IBDs), are chronic conditions with periods of exacerbation and remission. Patients with IBD experience clinical gastrointestinal (GI) symptoms, as well as the emotional burden that accompanies chronic conditions characterized by reduced quality of life and ability to work. With estimates of direct and indirect costs ranging between $14.6 and $31.6 billion in 2014, there is a significant healthcare burden associated with IBD. Although treatment expenses make up a significant portion of the cost of IBD, studies show that inappropriate treatment, lack of adherence to therapeutic regimens, or suboptimal treatment increase the cost burden. Costs for IBD include hospitalizations, the eventual need for surgery due to disease complications, and physician visits. The staggering economic burden of IBD makes early diagnosis, coupled with effective treatment at onset, imperative. Therefore, management of IBD must evolve beyond symptom control and toward sustained control of GI inflammation as measured by endoscopic, radiologic, and laboratory parameters.Treatment advances have made deep remission a realistic target for some people with IBD. However, achieving deep remission requires a shift in the management paradigm of IBD, encouraging individualized treatment with biologics that focuses less on treating symptoms and more on preventing potential disease progression. Although expensive at onset, this management strategy may ultimately lead to decreased rates of surgeries and hospitalizations, potentially yielding lower long-term costs for treatment. PMID- 27269906 TI - The wife of God. AB - The case was presented of an ultra-orthodox Jewish woman who believed that she is the wife of God. Such a belief may be normative in some religions, but not in Judaism, where closeness to God is understood as a metaphor. Although the patient's beliefs are not acceptable within ultra-orthodox beliefs, there are examples of such ideas within the history of religious Judaism. The deviance of her delusions from the religious norm would appear to be deceptively minor. The similarities in content and underlying factors with possession states such as dybbuk and maggid are considered. Being the wife of God may be understood in terms of her disappointments and represent gaining control over the uncontrollable in her life and society. The details of the case management are presented to demonstrate the importance of discussing her ideas with her and working with community authority figures while respecting their status and rulings. PMID- 27269907 TI - Functionalists and zombis: Sorcery as spandrel and social rescue. AB - At one level, anthropologists remain functionalists in that they generally see acts and institutions as contributing to a greater social whole only through which they make sense. Thus, sorcery accusations have been traditionally interpreted in terms of maintaining social harmony and cohesion. In the case of Haitian zombification, the zombi seems a locally misidentified victim who is frequently mentally ill. As a hapless non-agent, the zombi cannot initiate the sorcery accusations, so how do we understand the recognition and rescue of the zombi, either in terms of social function or social action? PMID- 27269905 TI - African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction. AB - AIM: This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. PATIENTS & METHODS: The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. RESULTS: Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1. CONCLUSION: Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers. PMID- 27269908 TI - From social liminality to cultural negotiation: Transformative processes in immigrant mental wellbeing. AB - The underlying psychosocial processes that produce immigrant mental wellbeing are understudied in anthropology and medicine. This paper provides insights into these processes by describing culturally diverse immigrants' perceptions of mental health and adaptation strategies. Qualitative data were collected from 21 focus groups as part of a large, multidisciplinary, participatory action research project about mental health with five ethnolinguistic groups (Mandarin-speaking Chinese, Polish, Punjabi Sikh, Somali and Spanish-speaking Latin American) in Ontario, Canada. In framing the analysis, transformative concepts are applied to address dimensions of power and culture - social liminality and cultural negotiation - to the ongoing psychosocial processes of coping with mental distress. 'Social liminality' describes how immigrants perceive themselves to be in a psychologically stressful, transitional state, whereas 'cultural negotiation' describes how they actively cope with cultural tensions and respond to mental health challenges. Study findings show that while social liminality and cultural negotiation are stressful, they also have the potential to help individuals adapt by producing a positive synthesis of ideas about mental health in new social and cultural contexts. The study contributes to the shift from problem identification using a biomedical model of mental illness to a more psychosocial and ecological approach that reveals the potential for resolving some mental health problems experienced in immigrant communities. Describing active psychosocial process of adaptation also reinforces the therapeutic and educational value of partnerships between practitioners and clients and immigrant communities and mental health systems. PMID- 27269909 TI - Practitioners, postnatal depression, and translation: An investigation into the representation of Bangladeshi mothers in the East End. AB - This paper is based on research that investigated the personal, localised and institutional representations of the emotional experiences of Bangladeshi mothers in Tower Hamlets, London. The research was conducted during 2003 and 2004. Whilst the London borough of Tower Hamlets is not deprived by global standards, within the UK the borough ranks very low on certain socio-economic indicators. Simultaneously, the 'East End' can still conjure up images of heart-warming kinship and of a place that welcomes migrants. These, and other contradictory depictions, are used by the people who both live and work in the borough. Through the investigation of the narratives of those who work with Bangladeshi mothers, this paper explores the role of culture as presented in both self-conscious and implicit terms. Further to this, it examines what claims are based on these conceptions. This analysis demonstrates that institutions are not neutral spaces in which identities and representations of experience are produced, but in fact shape the very nature of these identities and representations. As focal points this paper chooses health and motherhood as loci where personal experience, social institutions and notions of 'culture' all intersect. To stress only that the experience of motherhood is undeniably a feature of shared humanity would be to ignore the fact that reproduction is also culturally mediated and reconstructed. Through discussions such as those concerning the nature of 'postnatal depression', depicted as having both universal and culturally specific elements, debates around ethnicity and class are also brought into sharper focus. PMID- 27269910 TI - 'A person of two countries'. Life and health in exile: Somali refugees in Sweden. AB - Meeting and treating patients from other countries and cultures constitutes a challenge for health care. The number of immigrants and refugees has seen a rapid increase in recent years in Sweden. Expectations and experiences of health and illness often differ among these immigrant groups compared with the inhabitants of the majority society. This paper examines the situation of Somali refugees living in a multicultural suburban area of a large city in southern Sweden, and the aim was to illuminate and document their thoughts and experiences in relation to health and illness. Thirteen interviews with Somalis of different sexes and ages were conducted in the informant's homes. A hermeneutic-phenomenological approach was used in the analysis. The findings revealed an essential theme - a life in exile - that permeated every subject that was discussed and talked about. This was expressed in the following aspects: longing for the homeland, pain - a companion in exile, prejudice and discrimination, family - comfort and trouble, religion and beliefs in Jinns. Complex feelings of bi-nationality and of being uprooted were expressed. Prior knowledge about the hardships involved in a life as a refugee may allow and increase the possibilities for better communication, increased trust and mutual respect in order to achieve a meaningful encounter with health care personnel. PMID- 27269911 TI - Cultural interpretations of the efficacy and side effects of antimalarials in Tanzania. AB - This paper examines the cultural interpretations and the perceived efficacy and side effects of antimalarials in Tanzania. Interviews with 56 mothers of children diagnosed with malaria revealed that they were nostalgic about chloroquine, a banned antimalarial. Additional findings indicated that a majority of the mothers had an overall negative disposition toward sulfadoxine-pyrimethamine (SP), the first-line antimalarial. Mothers considered the persistence of fever as the primary undesirable side effect of SP, while also mentioning a range of other side effects. Mothers who could not afford an alternative to SP, rationalized the drug's side effects as indicative of disease egress. It is argued that ethnographic studies of cultural perceptions of malaria and antimalarials provide useful perspectives on how people negotiate the identity of a febrile illness, and how they understand and interpret the efficacy of existing antimalarials. In acknowledging the intra-cultural variability in perceptions of malaria and antimalarials, health policy makers must be cautious when implementing a 'one drug fits all' approach to malaria control. PMID- 27269912 TI - Translating malaria as sumaya: Justified convention or inappropriateness? AB - In exchanges between health professionals and consultants in the West African context, the word malaria is often replaced by its equivalent in the local dialect. In the Nouna health district of Burkina Faso the term malaria is regularly translated as sumaya. Acknowledging that there may be important epistemological differences between malaria, a term issued from the biomedical epistemology, and sumaya, which is borrowed from traditional medicine epistemology, the possible mismatches between these two terms have been assessed to anticipate problems that may result from their translation by different health stakeholders. By consulting various traditional healers and other members of the communities about the local meaning of the term sumaya, it has been possible to compare the conceptualisation of sumaya to the biomedical conceptualisation of malaria and assess the gap between them. An investigation based on a sample of 13 traditional healers and over 450 individuals from Nouna's health district was conducted to document the meaning of the term sumaya. This paper demonstrates that the generally accepted translation of the word malaria as sumaya is a mistake when one looks at the different systems of belief and representations given to each of these two terms. PMID- 27269913 TI - The moment of sale: Treating malaria in Abidjan, Cote d'Ivoire. AB - Beyond home care without active treatment, the first step of home-based management of malaria (HMM) is the health provider-customer interactions that often lead to the purchase of drugs or herbs to treat symptoms. In Abidjan, Cote d'Ivoire, the quality and content of such interactions in pharmacies where antimalarials are sold officially, with illegal drug vendors and with herbal medicine sellers, vary considerably. Commercial encounters associated with adult illness episodes of locally identified malaria, observed in 2004-5, illustrate that customers present to sales points, on behalf of people who are ill, with a pre-established diagnosis and the intent of purchasing medication with which they have prior familiarity. Customers sought neither diagnosis nor clarification, and communication between vendor and customer was limited to minimal enquiries or suggestions. These findings have important implications related to the need for vendor training to support HMM and so ensure prompt and appropriate treatment outside clinical settings. PMID- 27269914 TI - The power of place: geography, destiny, and globalization's rough landscape, by Harm de Blij. PMID- 27269915 TI - Impotent Warriors: Gulf War Syndrome, Vulnerability and Masculinity, by Susie Kilshaw. PMID- 27269916 TI - Els van Dongen (1946-2009), Editor, Anthropology & Medicine. PMID- 27269917 TI - Obesity indices for prediction of chronic kidney disease: ?a cross-sectional study in 26 655 Chinese adults. AB - OBJECTIVE: To investigate the associations between chronic kidney disease (CKD) and body mass index (BMI), waist circumference(WC), waist-to-height ratio (WheiR) in Chinese adults.? METHODS: A total of 26 655 participants, who voluntarily attended annual health examination at the Health Management Center in the Third Xiangya Hospital of Central South University from June 2013 to February 2014, were enrolled for this study. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed.? RESULTS: The prevalence rate of CKD was 9.6% and 3.1% in male and female subjects, respectively. Multivariate logistic regression analysis showed that BMI, WC and WheiR were independent risk factors for CKD in diabetic male and hypertensive male subjects (P<0.01). However, no association between these obesity indices and CKD was found in women after multivariate adjustment. In diabetic male subjects, when BMI>=28.7 kg/m(2), WC=90.7 cm and WheiR=0.56, the sensitivity and specificity prediction for CKD was 24.8%, 58.5%, 45.5% and 83.3%, 54.4%, 69.6%, respectively. In hypertensive male subjects, when the optimum cut-off points for BMI, WC and WheiR were >=?27.0 kg/m(2), 91.2 cm and 0.54, the sensibility prediction for CKD were 41.0%, 47.0% and 50.1%, respectively, while the specificity prediction were 68.0%, 63.0% and 61.4%, respectively. The area under the ROC curve of BMI, WC, WheiR for CKD prediction were 0.56, 0.57, 0.59 in diabetic male subjects and 0.54, 0.56, 0.57 in hypertensive male subjects, respectively.? CONCLUSION: BMI, WC and WheiR are associated with the increased risk for CKD in diabetic or hypertensive male subjects. However, the value for these obesity indices is limited in screening CKD. PMID- 27269918 TI - [Construction and identification of a lentiviral vector for RNA interference of human GLUT3 gene]. AB - OBJECTIVE: To construct an effective lentiviral vector for RNA interference (RNAi) with human glucose transporter 3 (GLUT3)gene.? METHODS: Four pairs of shRNA sequences against different parts of GLUT3-mRNA were separately cloned into the RNAi plasmid vector pLV-shRNA by recombinant DNA technology to construct shRNA expression vectors pLV-shRNA-GLUT3-1, pLV-shRNA-GLUT3-2, pLV-shRNA-GLUT3-3, and pLV-shRNA-GLUT3-4. The vectors were transfected into HeLa cells to detect the effectiveness of GLUT3 gene silencing. One of effective vectors was selected and co-transfected into 293T cells with lentivirus packaging plasmids to obtain packaged lentivirus particles LV-GLUT3. After viral titer determination, U251 glioblastoma cells were infected with LV-GLUT3 at a multiplicity of infection (MOI) of 10. Finally, the expression of GLUT3 protein was detected by Western blot. ? RESULTS: DNA sequencing demonstrated that the shRNA sequences were successfully inserted into the pLV-shRNA vectors. In HeLa cells, the expression of GLUT3-mRNA was significantly down-regulated by the recombinant vectors compared with negative control. The recombinant lentivirus LV-GLUT3 harvested from 293T cells had a titer of 1.5*10(9) TU/mL. After infection with LV-GLUT3, the expression of GLUT3 protein in U251 glioblastoma cells was down-regulated. ? CONCLUSION: An effective lentiviral shRNA expression vector targeting the GLUT3 gene is successfully constructed and can be used for further study on the functions of GLUT3 gene. PMID- 27269919 TI - [Effects of 7-difluoromethy-5, 4'-dimethoxygenistein on proliferation and apoptosis of human cervical cancer cells and its mechanism]. AB - OBJECTIVE: To investigate the effects of 7-difluoromethy-5, 4'- dimethoxygenistein (DFMG) on inhibiting proliferation and inducing apoptosis of human cervical cancer HeLa cells and its possible molecular mechanism in vitro.? METHODS: HeLa cells were cultured in vitro. The effect of DFMG on inhibiting proliferation was determined using MTT assay. The effects of DFMG on inducing apoptosis were assessed using flow cytometry with AV-PI staining, AO/EB staining, and agarose gel electrophoresis. Multiple molecular techniques, such as RT-PCR, Western blot, siRNA transfection, and cDNA transfection, were used to explore its possible molecular mechanism.? RESULTS: DFMG presented with dramatically inhibiting proliferation effect of HeLa cells in a time-and dose-dependent manner ranging from 0.25 to 64 MUg/mL and from 24 to 72 h in vitro, and its IC(50) was 4.62 MUg/mL for 48 h. The cells treated with DFMG for 48 h showed typical morphological change of apoptosis, typical DNA ladder of agarose gel electrophoresis, and the sub-G(1) population increased in a dose-dependent manner. Simultaneously the expressions of c-myc mRNA, c-myc protein and its downstream genes, such as bax, cyto-c and caspase-9, were up-regulated, while bcl 2 protein was down-regulated. Down-regulation of c-myc by siRNA attenuated DFMG induced cell proliferation inhibition and inducing apoptosis. Up-regulation expression of c-myc by cDNA transfection could enhance the effects of DFMG induced cell proliferation inhibition and inducing apoptosis.? CONCLUSION: DFMG could inhibit the proliferation and induce the apoptosis of human cervical cancer HeLa cells in vitro, and its mechanism may be closely related to regulate c-myc and its down-stream gene expression. PMID- 27269920 TI - [Correlation between cyclin-dependent kinase inhibitor p27kip1 and trastuzumab resistance in gastric cancer]. AB - OBJECTIVE: To investigate the correlation between cyclin-dependent kinase inhibitor p27kip1 and trastuzumab-resistance in gastric cancer.? METHODS: We selected HER2-overexpressed human gastric cancer cell line NCI-N87 to establish trastuzumab-resistant NCI-N87/TR cell line by stepwise exposure to different doses of trastuzumab. The 50% inhibitory concentration (IC(50)) of trastuzumab and resistance index (RI) were calculated or analyzed by MTT assay. The expression levels of cdk2 and p27kip1 were detected by Western blot. After the treatment with cdk2 inhibitor (Purvalanol A), the expression levels of relevant proteins in NCI-N87/TR cells were detected by Western blot, and the sensitivity to trastuzumab was analyzed by MTT assay. ? RESULTS: Compared with NCI-N87 cells, the expression of cdk2 was significantly increased in NCI-N87/TR cells (P<0.001), while the expression of p27kip1 showed a significant decrease (P<0.001). Restoration of the p27kip1 protein expression by cdk2 inhibitor (Purvalanol A) increased the sensitivity of NCI-N87/TR to trastuzumab.? CONCLUSION: Down regulation of p27kip1 might be a mechanism for triggering trastuzumab resistance to gastric cancer cell line NCI-N87. PMID- 27269921 TI - [Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells]. AB - OBJECTIVE: To evaluate whether dexmedetomidine hydrochloride, an alpha(2) adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.? METHODS: H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-alpha in the culture medium were assessed by corresponding kits.? RESULTS: Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-alpha release in the culture supernatant. Yohimbine, an alpha(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.? CONCLUSION: Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of alpha(2)-adrenergic receptors. PMID- 27269922 TI - [Expression of cyclophilin A/CD147 in carotid atherosclerotic plaque and the intervention of atorvastatin]. AB - OBJECTIVE: To explore the expression of CyPA and CD147 in rabbit models of vulnerable carotid atherosclerotic plaque and the therapeutic effect of atorvastatin.? METHODS: Twenty-four male New Zealand rabbits were randomly divided into 3 groups. Eight rabbits were served as a normal diet group (Group A), and the remaining 16 rabbits underwent balloon-induced endothelial injury in the right carotid artery and thereafter were fed on high-cholesterol diet (1% cholesterol) for 12 weeks, then they were divided into 2 groups: a AS group (Group B), an atorvastatin group [Group C, 2.5 mg/(kg.d)]. 4 weeks later, plaque disrupture was triggered by China Russell's viper venom and histamine. Serum levels of TC, TG, LDL-C and HDL-C were measured at different timepoint. The damaged carotid arteries were collected to undergo pathological examination. The macrophage, expression of CyPA and CD147 were detected by immuno-histochemical analysis, and the mRNA levels of CyPA and CD147 were examined by reverse transcription polymerase chain reaction (RT-PCR).? RESULTS: Compared with the Group A, the serum levels of TC and LDL-c in the Group B and Group C were significantly increased (all P<0.01). Compared with the Group B, the serum levels of TC and LDL-c in the Group C were reduced significantly after atorvastatin intervention for 4 weeks (all P<0.01). The plaques disruption and thrombosis occurred in 4 out of the 6 rabbits in the Group B, while only 1 rabbit demonstrated plaques disruption and thrombosis in the Group C. Compared with the Group B, the levels of CyPA, CD147 and macrophage in carotid atherosclerotic plaque in the Group C were decreased significantly (all P<0.01).? CONCLUSION: The up-regulation of CyPA and CD147 may be involved in pathogenesis of vulnerable carotid atherosclerotic plaque. Atorvastatin could stabilize the plaque through inhibiting the CyPA and CD147 expression. PMID- 27269923 TI - [Effect of bone marrow mesenchymal stem cells? on angiogenesis in rats after brain injury]. AB - OBJECTIVE: To explore the effect of bone marrow mesenchymal stem cells (BM-MSCs) on angiogenesis in rats after brain injury. ? METHODS: Brain injury model of rats was established with freely fall method. A total of 50 Sprague-Dawley (SD) rats were randomly divided into a transplanted group and a control group (n=25 in each group). BM-MSCs were injected in lateral ventricle in the transplanted group, and normal saline was injected in the control group. Modified method for neurological deficit scores (mNSS) was performed at the 1, 3, 7, 21, 14 d after the operation. Flow cytometry were performed to detect CD34 and CD133 double-labeled peripheral blood cells in preoperative or 3, 6, 12, 24 h, and 3, 7 d after the operation. Expression of neuron-specific enolase (NSE) and CD31 in the brain tissues near injury area was detected by immunohistochemical SP method. ? RESULTS: There was significant difference in the MNSS scores between the 2 groups (F=5.997, P<0.05), and the difference at the different time points in each group was significant (F=37.106, P<0.01). The mNSS scores in the control group were higher than those in the transplanted group at the 7, 14, 21 d after the operation (P<0.05). The CD34 and CDl33 double positive cells (DPCs) were present in rats' peripheral blood. DPCs's numbers in peripheral blood in the control group were declined at 3 h after the sugery, they were increased and reached the highest point at 6 h after the surgery, and decreased gradually and reached normal levels at 24 h after the surgery. The same tendency was achieved in the transplanted group, and the DPCs's numbers were increased until 24 h after the surgery, which were significantly higher in the transplanted group than those in the control group at 24 h after the surgery (P<0.05). The NSE expression in the transplanted group was significantly greater than that in the control group in 7 and 14 d after the surgery (P<0.05). The expression of CD31 in the transplanted group was significantly higher than that in the control group in 3 and 7 d after the surgery (P<0.05).? CONCLUSION: BM-MSCs transplantation can increase the number of peripheral blood endothelial progenitor cells after traumatic brain injury in rats and sustain for 24 h, which in turn up-regulate the angiogenesis and neuronal marker, and improve the neurological function. PMID- 27269925 TI - [Level of serum phosphorus and adult type 2 ?diabetes mellitus]. AB - OBJECTIVE: To determine effects of the serum levels of phosphorus, calcium and magnesium on patients with type 2 diabetes mellitus.? METHODS: A total of 244 hospitalized patients were enrolled from 2014 to 2015, and they were assigned into a type 2 diabetic group (n=162) and control group (n=82). The serum levels of phosphorus, calcium and magnesium were determined. The correlations between blood levels of glucose and the serum levels of phosphorus, calcium or magnesium were analyzed. ? RESULTS: The serum level of phosphate in type 2 diabetic group was significantly lower than that in the control group (P<0.05). There was no significant difference in the level of serum calcium and magnesium between the two groups. In the type 2 diabetic group, there was no significant correlation between the level of blood glucose and the serum level of phosphorus, calcium or magnesium. In the control group, the blood glucose and serum levels of phosphorus were positively correlated (r=0.226, P=0.042), but there was no significant correlation between the level of blood glucose and the serum level of calcium or magnesium.? CONCLUSION: Serum level of phosphorus is obviously decreased in type 2 diabetes patients, indicating that they may have a disorder in phosphorus metabolism. PMID- 27269924 TI - [Effects of hydrogen sulfide on contraction capacity of diaphragm from type 1 diabetic rats]. AB - OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on contraction capacity of diaphragm in type 1 diabetic rats.? METHODS: Thirty-two male SD rats were randomly divided into a normal group (NC), a diabetic group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8). Intraperitoneal injection of streptozotocin was utilized to establish diabetic rat model. After the modeling, the rats in the DM+NaHS and the NaHS groups were intraperitoneally injected with 28 MUmol/kg NaHS solution. 8 weeks later, the diaphragm contractility was assessed by isolated draphragm strips perfusion. The peak twitch tension (Pt), maximum tetanic tension (Po) and maximal rates of contraction/relaxation (+/-dT/dtmax) were determined. The alterations in diaphragm ultrastructure were observed under electron microscopy. The diaphragm weight/body weight (DW/BW) was measured. The activities of succinic dehydrogenase (SDH), lactate dehydrogenase (LDH) and sarcoplasmic reticulum Ca2+ ATPase (SERCA) were analyzed by spectrophotometric method. The mRNA levels of SERCA and prospholamban (PLB) in diaphragm were detected by RT-PCR.? RESULTS: Compared with the NC group, there was no significant change in all measured index in the NaHS group (P>0.05), while Pt, Po and +/-dT/dtmax were significantly decreased in the DM group (P<0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the diaphragm. The DW/BW ratio and the activities of SDH, LDH and SERCA were decreased. The SERCA mRNA was decreased, while PLB mRNA was increased. Compared with the DM group, the diaphragm contractility and ultrastructure damage were improved in the DM+NaHS group. The DW/BW ratio and the activities of SDH, LDH and SERCA were increased. The SERCA mRNA was increased, while PLB mRNA was decreased (all P<0.05).? CONCLUSION: H(2)S can enhance the contraction capacity of diaphragm in type 1 diabetic rats, which is involved in regulating the activities of biological enzymes and the gene expressions of calcium regulatory proteins. PMID- 27269927 TI - [Effect of pre-transplant donor specific antibody on antibody-mediated rejection and graft dysfunction]. AB - OBJECTIVE: To explore the effect of pre-transplant donor specific antibody (DSA) on antibody-mediated rejection (AMR) and function of transplanted kidney.? METHODS: A total of 88 cases of renal transplant recipients were selected. Before surgery, DSA was examined by Luminex liquid phase chip in renal transplant recipients. The recipients were divided into a DSA positive group (n=20) and a DSA negative group (n=68). The follow-up time was 2 years. After the operation, the pathologic morphology of the transplanted kidney was evaluated and classified according to the Banff 2005 standard. The situation for the transplanted kidney was evaluated.? RESULTS: The incidence of AMR in the DSA positive group and negative group was 20% and 1.5%, respectively, with significant difference between them (P<0.01). The incidence of graft loss in the DSA positive group and negative group was 15% and 1.5%, respectively, with significant difference between them (P<0.05). The pre-transplant DSA associated with AMR at multiple mean fluorescence intensity (MFI) was obvious different from that without AMR (P<0.01). Receiver operating characteristic (ROC) curves showed that the maximal MFI threshold for recipients with AMR was 7909.5 after renal transplantation. There was no significant difference in the delayed recovery of renal graft function (DGF) between the 2 groups (P>0.05).? CONCLUSION: The detection of DSA level before renal transplantation can predict the risk of AMR and the function of transplanted kidney. The MFI intercept point of the highest DSA (MFI>?7909.5) can be used to predict the risk of AMR. PMID- 27269926 TI - [Effect of epidermal growth factor and testosterone on androgen receptor activation in urethral plate fibroblasts in hypospadias]. AB - OBJECTIVE: To investigate androgen receptor (AR) expression and the effect of epidermal growth factor (EGF) and testosterone on AR expression level.? METHODS: EGF or different concentrations of testosterone were incubated with the primary urethral plate fibroblasts from patients with hypospadias. The levels of AR expression in the fibroblasts were detected by immunocytochemical assays and graphical analysis.? RESULTS: There was no significant difference in AR activation under physiological concentrations (3*10(-8) mol/L) of testosterone between the control and the distal hypospadias group (P>0.05). However, there was a significant decrease in AR activation in the proximal hypospadias group compared to that in the control group (P<0.001). Under the concentration of 3*10( 6) mol/L, the effects of testosterone on AR activation were dramatically different in the three groups (control group>distal hypospadias group>proximal hypospadias group, P<0.001). AR activation level in the group of proximal hypospadias was improved most obviously when EGF and physiological concentration of testosterone were employed in the urethral plate fibroblasts from hypospadias patients (P<0.001), and it was improved more in the distal hypospadias group than that in the control group (P=0.02).? CONCLUSION: AR expression and activation in the urethral plate fibroblasts from hypospadias patients are abnormal. EGF can be used to improve AR activation in fibroblasts from different types of hypospadias, especially in the proximal type. PMID- 27269928 TI - [Study on out-of-pocket expenditure and related factors among cancer inpatients with Hunan Provincial Urban Employee Basic Medical Insurance]. AB - OBJECTIVE: To explore the level and influential factors for out-of-pocket (OOP) expenditure regarding Hunan Provincial Urban Employee Basic Medical Insurance (UEBMI) and to provide evidence for improvement of medical insurance payment system.? METHODS: Stratified random sampling method was used to obtain 10 527 records of cancer inpatients from January 2011 to December 2014. Social demographic and expenditure information were collected from UEBMI information system. The proportion of OOP expenditure for inpatient and each part of the cost was described. Multiple linear regression was used to analyze main related factors of OOP expenditure.? RESULTS: The median proportion of OOP for inpatients costs was 20.11%, and remained stable from 2011 to 2014. The main related factors for OOP expenditure were age, civil servant, retirment status, hospital level, cost of hospitalization, hospitalization duration, medicine cost, proportion of general medical service charges, treatment cost, expenses of examination and laboratory test, and cancer type.? CONCLUSION: OOP expenditure among UEBMI cancer inpatients was under control and stable. The level can well reflect the policy preferences. It could be further improved through the control of related factors, particularly the hospital level. PMID- 27269929 TI - [Meta analysis for interventional effect on unexpected injury among children and adolescents in China]. AB - OBJECTIVE: To comprehensively evaluate the interventional effect on unexpected injury among children and adolescents in China, and to provide scientific basis for the injury control strategy.? METHODS: Meta analysis was utilized to analyze the selected literatures. After heterogeneity test of the data, a relevant model was chosen to estimate the combined effect values relative risk (RR) and the corresponding 95% confidence interval (95% CI). Subgroup analysis were performed based on the intervention measures, objects and places. Sensitivity and publication bias were analyzed.? RESULTS: A total of 18 papers were included in the Meta analysis with a sample size of 32 599. The combined RR value was 0.54 (95% CI 0.44 to 0.68). Subgroup analysis showed that the RR value of health education and comprehensive intervention were 0.59 and 0.50, respectively, with no significant difference between them (P>0.05). The RR values of the interventions in school alone, in school and community or in community alone were 0.51, 0.78 or 0.63. The RR values on children alone, children and parents or parents alone were 0.53, 0.65 or 0.35. The differences were significant when the interventions were performed among different places or objects (P<0.05). Sensitivity analysis revealed that meta-analysis results were relatively stable.? CONCLUSION: The targeted interventions were significant in the prevention of unexpected injuries among children and adolescents. It is worth further promoting and spreading. PMID- 27269930 TI - [Study on the situation regarding endoscope cleaning and disinfection in the department of otolaryngology in Hunan hospitals]. AB - OBJECTIVE: To investigate the situation regarding the cleaning and sterilization of endonasal endoscopes in department of otolaryngology in Hunan Province, and to provide strategy for improving the level of sterilization and management of endonasal endoscopes.? METHODS: A total of 100 medical institutions were investigated by spot assessment, check and sampling. Data was analyzed by multivariate analysis.? RESULTS: The qualified rate of rules and regulations for endoscopy was 28.8% in the second-class hospitals and 45% in the top-class hospitals. The qualified rate of environment for endoscopy cleaning and sterilization was 36.3% in the second-class hospitals and 85% in the top-class hospitals. The main problems include lack of independent disinfection room, the space not large enough, and/or lack of ventilation system. The qualified rate of bacterial detection for post-sterilized endoscopes and biopsy forceps was 93.8% in the second-class hospitals and 95.0% in the top-class hospitals, and the main pathogenic bacteria was gram-positive cocci and gram-negative bacilli. The multivariate analysis showed that the influencial factors for endoscope cleaning and disinfection are as follows: staffs responsible for the cleaning and sterilization of otolaryngology endoscopes, the standard for cleaning and disinfection process, and the frequency of endoscope use.? CONCLUSION: The present situation of cleaning and sterilization for otolaryngology endoscopes is better in the top-class hospitals than that in the second-class hospitals. The sterilization and management of otolaryngology endoscopy are needed to be improved, and the staff training is needed, especially in the primary hospitals. PMID- 27269931 TI - [Treatment of cryptococcal meningitis by use of shunting and review in literature]. AB - OBJECTIVE: To evaluate the time and effect of shunt operation on cryptococcal meningitis.? METHODS: A total 7 patients received shunt operation for the therapy of cryptococcal meningitis patients and the data was retrospectively analyzed.? RESULTS: Intracranial hypertension-caused symptoms were resolved immediately. There was no complication, no infection dissemination and no recrudescence of cryptococcal meningitis. ? CONCLUSION: Shunt operation is effective for intracranial hypertension caused by cryptococcal meningitis. It does not affect the antifungal treatment. PMID- 27269932 TI - [A case of retroperitoneal Castleman's disease with paraneoplastic pemphigus]. AB - Paraneoplastic pemphigus is a rare autoimmune bullous dermatosis, which is caused by potential neoplasm, especially the Castleman's disease. Castleman's disease associated with paraneoplastic pemphigus is misdiagnosed frequently and easily in clinical practices. Furthermore, it is reported that the mortality rate for this disease is very high. Bronchiolitis obliterans is the most common complication and the most important cause of death. There was a female patient presenting recalcitrant mucocutaneous erosions, ulcers and scattered erythemas in the body. The patient was diagnosed and treated for pemphigus vulgaris with little success in Xiangya Hospital, Central South University in January 2015. Further investigations confirmed the diagnosis of paraneoplastic pemphigus with retroperitoneal tumor. Subsequently, the patient was treated with tumor resection in combination with intravenous immunoglobulin and corticosteroids. The pathology revealed that it was the Castleman's disease. Her mucocutaneous performance recovered obviously and the bronchiolitis obliteran did not appear in the follow up. Castleman's disease associated with paraneoplastic pemphigus should be considered when mucosal and skin lesions showing no improvement under corticosteroids. Early and complete removal of the tumor together with immunotherapy could be beneficial to the patient's prognosis. PMID- 27269933 TI - Heartbeat: Go with the flow in aortic stenosis? PMID- 27269934 TI - Abnormal screening chest radiograph in a 21-year-old male. AB - CLINICAL INTRODUCTION: A 21-year-old male with a medical history of scoliosis was referred for an abnormal chest radiograph performed on screening (figure 1). He was asymptomatic with good exercise tolerance. Blood pressure and heart rate were normal. The heart sounds were normal. The pulmonary examination was unremarkable. A treadmill test performed 3 years prior for atypical chest pain was normal. An ECG performed was also normal. QUESTION: What abnormality is present in the chest radiograph? DextrocardiaEnlarged right heart borderMediastinal massProminent pulmonary vasculatureSitus inversus. PMID- 27269935 TI - Erratum: Development of the atrial septum. PMID- 27269936 TI - Dyspnoea in a 36-year-old woman. PMID- 27269938 TI - Regarding Beau. PMID- 27269937 TI - Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. AB - PURPOSE: To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), and the role of PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC). METHODS: A phase 1/2 multicenter, open-label study is being conducted in patients with inoperable or metastatic solid tumors. We report here the results from the UBC expansion cohort. Durvalumab (MEDI4736, 10 mg/kg every 2 weeks) was administered intravenously for up to 12 months. The primary end point was safety, and objective response rate (ORR, confirmed) was a key secondary end point. An exploratory analysis of pretreatment tumor biopsies led to defining PD L1-positive as >= 25% of tumor cells or tumor-infiltrating immune cells expressing membrane PD-L1. RESULTS: A total of 61 patients (40 PD-L1-positive, 21 PD-L1-negative), 93.4% of whom received one or more prior therapies for advanced disease, were treated (median duration of follow-up, 4.3 months). The most common treatment-related adverse events (AEs) of any grade were fatigue (13.1%), diarrhea (9.8%), and decreased appetite (8.2%). Grade 3 treatment-related AEs occurred in three patients (4.9%); there were no treatment-related grade 4 or 5 AEs. One treatment-related AE (acute kidney injury) resulted in treatment discontinuation. The ORR was 31.0% (95% CI, 17.6 to 47.1) in 42 response evaluable patients, 46.4% (95% CI, 27.5 to 66.1) in the PD-L1-positive subgroup, and 0% (95% CI, 0.0 to 23.2) in the PD-L1-negative subgroup. Responses are ongoing in 12 of 13 responding patients, with median duration of response not yet reached (range, 4.1+ to 49.3+ weeks). CONCLUSION: Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1 positive patients with UBC, many of whom were heavily pretreated. PMID- 27269939 TI - Comparative Effectiveness of Treatment Strategies for Bladder Cancer With Clinical Evidence of Regional Lymph Node Involvement. AB - PURPOSE: Patients with bladder cancer with clinical lymph node involvement (cN+) are at high risk for distant metastases, but are potentially curable. Such patients are excluded from neoadjuvant chemotherapy trials and pooled with patients with distant metastases in first-line chemotherapy trials not suited to define the role of combined-modality therapy. To address this evidence void, we performed a comparative effectiveness analysis. METHODS: We included cTanyN1-3M0 bladder cancer patients from the National Cancer Data Base (2003-2012) treated with chemotherapy and/or cystectomy. We used multistate survival analysis, allowing for delayed entry, to assess overall survival (OS) according to various treatment strategies. Effectiveness was estimated with multivariable adjustment for tumor-, patient-, and facility-level characteristics. RESULTS: Among 1,739 patients (cN1, 48%; cN2, 45%; cN3, 7%), 1,104 underwent cystectomy and 635 were treated with chemotherapy alone. Of the cystectomy patients, 363 received preoperative and 328 received adjuvant chemotherapy. The crude 5-year OS for chemotherapy alone, cystectomy alone, preoperative chemotherapy followed by cystectomy, and cystectomy followed by adjuvant chemotherapy was 14% (95% CI, 11% to 17%), 19% (95% CI, 15% to 24%), 31% (95% CI, 25% to 38%), and 26% (95% CI, 21% to 34%), respectively. Compared with cystectomy alone, preoperative chemotherapy was associated with a significant improvement in OS (hazard ratio, 0.80; 95% CI, 0.66 to 0.97). Adjuvant chemotherapy was also associated with a significant improvement in survival compared with cystectomy alone. The survival of patients treated with chemotherapy alone was worse than those treated with cystectomy alone. CONCLUSION: A subset of patients with cN+ bladder cancer achieves long term survival. Combined-modality therapy, with chemotherapy and cystectomy, is associated with the best outcomes. PMID- 27269940 TI - T-Cell Therapy Using Interleukin-21-Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression. AB - Purpose Peripheral blood-derived antigen-specific cytotoxic T cells (CTLs) provide a readily available source of effector cells that can be administered with minimal toxicity in an outpatient setting. In metastatic melanoma, this approach results in measurable albeit modest clinical responses in patients resistant to conventional therapy. We reasoned that concurrent cytotoxic T-cell lymphocyte antigen-4 (CTLA-4) checkpoint blockade might enhance the antitumor activity of adoptively transferred CTLs. Patients and Methods Autologous MART1 specific CTLs were generated by priming with peptide-pulsed dendritic cells in the presence of interleukin-21 and enriched by peptide-major histocompatibility complex multimer-guided cell sorting. This expeditiously yielded polyclonal CTL lines uniformly expressing markers associated with an enhanced survival potential. In this first-in-human strategy, 10 patients with stage IV melanoma received the MART1-specific CTLs followed by a standard course of anti-CTLA-4 (ipilimumab). Results The toxicity profile of the combined treatment was comparable to that of ipilimumab monotherapy. Evaluation of best responses at 12 weeks yielded two continuous complete remissions, one partial response (PR) using RECIST criteria (two PRs using immune-related response criteria), and three instances of stable disease. Infused CTLs persisted with frequencies up to 2.9% of CD8+ T cells for as long as the patients were monitored (up to 40 weeks). In patients who experienced complete remissions, PRs, or stable disease, the persisting CTLs acquired phenotypic and functional characteristics of long-lived memory cells. Moreover, these patients also developed responses to nontargeted tumor antigens (epitope spreading). Conclusion We demonstrate that combining antigen-specific CTLs with CTLA-4 blockade is safe and produces durable clinical responses, likely reflecting both enhanced activity of transferred cells and improved recruitment of new responses, highlighting the promise of this strategy. PMID- 27269941 TI - Chemotherapy Pharmacodynamics and Neuroimaging and Neurocognitive Outcomes in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia. AB - PURPOSE: To examine associations among methotrexate pharmacodynamics, neuroimaging, and neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on a contemporary chemotherapy-only protocol. PATIENTS AND METHODS: This longitudinal study linked pharmacokinetic assays collected during therapy to neurocognitive and brain imaging outcomes during long-term follow-up. A total of 218 (72.2%) of 302 eligible long-term survivors were recruited for outcome studies when they were more than 5 years post-diagnosis and older than 8 years of age. At long-term follow-up, survivors were an average of 13.8 years old and 7.7 years from diagnosis, and 51% were male. Neurocognitive testing, functional magnetic resonance imaging (MRI) during an executive function task, and structural MRI with diffusion tensor imaging were conducted. Generalized linear models were developed to identify predictors, and models were adjusted for age at diagnosis, sex, and parent education. RESULTS: Intelligence was within normal limits (mean, 98; standard deviation, 14) compared with population expectations (mean, 100; standard deviation, 15), though measures of executive function, processing speed, and memory were less than population means (all P < .02 after correction for false discovery rates). Higher plasma concentration of methotrexate was associated with a poorer executive function score (P < .02). Higher plasma methotrexate was also associated with higher functional MRI activity, with thicker cortices in dorsolateral prefrontal brain regions, and with white matter microstructure in the frontostriatal tact. Neurocognitive impairment was associated with these imaging findings as well. Associations did not change after adjustment for age or dose of leucovorin rescue. CONCLUSION: Survivors of childhood acute lymphoblastic leukemia treated on contemporary chemotherapy-only protocols demonstrate executive dysfunction. A higher plasma concentration of methotrexate was associated with executive dysfunction as well as with a thicker cortex and higher activity in frontal brain regions, regions often associated with executive function. PMID- 27269942 TI - Double-Blind, Placebo-Controlled, Randomized Phase III Trial Evaluating Pertuzumab Combined With Chemotherapy for Low Tumor Human Epidermal Growth Factor Receptor 3 mRNA-Expressing Platinum-Resistant Ovarian Cancer (PENELOPE). AB - PURPOSE: The AGO-OVAR 2.29/ENGOT-ov14/PENELOPE prospectively randomized phase III trial evaluated the addition of pertuzumab to chemotherapy in patients with platinum-resistant ovarian carcinoma with low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression. We report the results of the primary efficacy analysis. PATIENTS AND METHODS: Eligible patients had ovarian carcinoma that progressed during or within 6 months of completing four or more platinum cycles, centrally tested low tumor HER3 mRNA expression (concentration ratio <= 2.81 by quantitative reverse transcriptase polymerase chain reaction on cobas z480 [Roche Molecular Diagnostics, Pleasanton, CA]), and no more than two prior lines of chemotherapy. After investigators' selection of the chemotherapy backbone (single agent topotecan, weekly paclitaxel, or gemcitabine), patients were randomly assigned to also receive either placebo or pertuzumab (840-mg loading dose followed by 420 mg every 3 weeks). Stratification factors were selected chemotherapy, prior antiangiogenic therapy, and platinum-free interval. The primary end point was independent review committee-assessed progression-free survival (PFS). Additional end points included overall survival, investigator assessed PFS, objective response rate, safety, patient-reported outcomes, and translational research. RESULTS: Overall, 156 patients were randomly assigned. Adding pertuzumab to chemotherapy did not significantly improve independent review committee-assessed PFS for the primary analysis (stratified hazard ratio, 0.74; 95% CI, 0.50 to 1.11; P = .14; median PFS, 4.3 months for pertuzumab plus chemotherapy v 2.6 months for placebo plus chemotherapy). Sensitivity analyses and secondary efficacy end point results were consistent with the primary analysis. The effect on PFS favoring pertuzumab was more pronounced in the gemcitabine and paclitaxel cohorts. No new safety signals were seen. CONCLUSION: Although the primary objective was not met, subgroup analyses showed trends in PFS favoring pertuzumab in the gemcitabine and paclitaxel cohorts, meriting further exploration of pertuzumab in ovarian cancer. PMID- 27269944 TI - Efficacy of High-Intensity Local Treatment for Metastatic Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Analysis From the National Cancer Data Base. AB - Purpose Evidence from studies of other malignancies has indicated that aggressive local treatment (LT), even in the presence of metastatic disease, is beneficial. Against a backdrop of stagnant mortality rates for metastatic urothelial carcinoma of the bladder (mUCB) at presentation, we hypothesized that high intensity LT of primary tumor burden, defined as the receipt of radical cystectomy or >= 50 Gy of radiation therapy delivered to the bladder, affects overall survival (OS). Patients and Methods We identified 3,753 patients within the National Cancer Data Base who received multiagent systemic chemotherapy combined with high-intensity versus conservative LT for primary mUCB. Patients who received no LT, transurethral resection of the bladder tumor alone, or < 50 Gy of radiation therapy delivered to the bladder were included in the conservative LT group. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients who received high-intensity versus conservative LT. Results Overall, 297 (7.91%) and 3,456 (92.09%) patients with mUCB received high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer in the high-intensity LT group than in the conservative LT group (14.92 [interquartile range, 9.82 to 30.72] v 9.95 [interquartile range, 5.29 to 17.08] months, respectively; P < .001). Furthermore, in IPTW-adjusted Cox regression analysis, high-intensity LT was associated with a significant OS benefit (hazard ratio, 0.56; 95% CI, 0.48 to 0.65; P < .001). Conclusion We report an OS benefit for individuals with mUCB treated with high-intensity versus conservative LT. Although the findings are subject to the usual biases related to the observational study design, these preliminary data warrant further consideration in randomized controlled trials, particularly given the poor prognosis associated with mUCB. PMID- 27269945 TI - Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial. AB - PURPOSE: Although nonpharmacologic anti-infective measures are widely used in children treated for acute myeloid leukemia (AML), there is little evidence of their effectiveness. PATIENTS AND METHODS: We analyzed infectious complications in children during intensive treatment of AML according to the AML-BFM 2004 trial and surveyed sites on institutional standards regarding recommended restrictions of social contacts (six items), pets (five items), and food (eight items). A scoring system was developed with a restriction score for each item. Multivariable Poisson regression adjusted for sex, age, weight group, risk stratification, and prophylactic antibiotics was used to estimate the impact of the restrictions on the incidence ratios of fever of unknown origin, bacteremia, pneumonia, and gastroenteritis. RESULTS: Data on recommendations of nonpharmacologic anti-infective measures and infectious complications were available in 339 patients treated in 37 institutions. Analyses did not demonstrate a significant benefit of any of the restrictions regarding food, social contacts, and pets on the risk of fever, bacteremia, pneumonia, and gastroenteritis. In contrast, age, weight group, risk stratification, and nonabsorbable antibiotics had some influence on infections complications. CONCLUSION: The lack of effectiveness of dietary restrictions and restrictions regarding social contacts and pets should result in reconsideration of anti infective policies. PMID- 27269943 TI - Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis. AB - PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence. PMID- 27269946 TI - Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. AB - PURPOSE: ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor-positive advanced breast cancer. MATERIALS AND METHODS: In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. RESULTS: In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). CONCLUSION: ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required. PMID- 27269947 TI - Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. AB - PURPOSE: Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies. METHODS: In this phase I, open-label, dose escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression. RESULTS: Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks. CONCLUSION: Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing. PMID- 27269949 TI - Evaluation of the Risk of Relapse in Classical Hodgkin Lymphoma at Event-Free Survival Time Points and Survival Comparison With the General Population in British Columbia. AB - PURPOSE: Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC). METHODS: The BC Cancer Agency Lymphoid Cancer Database was screened to identify all patients age 16 to 69 years diagnosed with cHL between 1989 and 2012 treated with the chemotherapy regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (or equivalent). We compared the observed mortality to the general population using age-, sex-, and calendar period-generated expected mortality rates from BC life-tables. Relative survival was calculated using a conditional approach and expressed as a standardized mortality ratio of observed-to-expected deaths. RESULTS: One thousand four hundred two patients were identified; 749 patients were male (53%), the median age was 32 years, and 68% had advanced-stage disease. The median follow-up time was 8.4 years. Seventy-two percent of relapses occurred within the first 2 years of diagnosis. For all patients, the 5-year risk of relapse from diagnosis was 18.1% but diminished to 5.6% for patients remaining event free at 2 years. For advanced-stage patients who were event free at 2 years, the 5-year risk of relapse was only 7.6%, and for those who were event free at 3 years, it was comparable to that of limited-stage patients (4.1% v 2.5%, respectively; P = .07). Furthermore, international prognostic score >= 4 and bulky disease were no longer prognostic in patients who were event free at 1 year. Although the relative survival improved as patients remained in remission, it did not normalize compared with the general population. CONCLUSION: Patients with cHL who are event free at 2 years have an excellent outcome regardless of baseline prognostic factors. All patients with cHL had an enduring increased risk of death compared with the general population. PMID- 27269950 TI - Successful Therapy Reduction and Intensification for Childhood Acute Lymphoblastic Leukemia Based on Minimal Residual Disease Monitoring: Study ALL10 From the Dutch Childhood Oncology Group. AB - PURPOSE: Outcome of childhood acute lymphoblastic leukemia (ALL) improved greatly by intensifying chemotherapy for all patients. Minimal residual disease (MRD) levels during the first months predict outcome and may select patients for therapy reduction or intensification. METHODS: Patients 1 to 18 years old with ALL were stratified on the basis of MRD levels after the first and second course of chemotherapy. Thereafter, therapy was substantially reduced in patients with undetectable MRD (standard risk) and intensified in patients with intermediate (medium risk) and high (high risk) levels of MRD. Seven hundred seventy-eight consecutive patients were enrolled. The method of analysis was intention-to treat. Outcome was compared with historical controls. RESULTS: In MRD-based standard-risk patients, the 5-year event-free survival (EFS) rate was 93% (SE 2%), the 5-year survival rate was 99% (SE 1%), and the 5-year cumulative incidence of relapse rate was 6% (SE 2%). The safety upper limit of number of observation years was reached and therapy reduction was declared safe.MRD-based medium-risk patients had a significantly higher 5-year EFS rate (88%, SE 2%) with therapy intensification (including 30 weeks of asparaginase exposure and dexamethasone/vincristine pulses) compared with historical controls (76%, SE 6%). Intensive chemotherapy and stem cell transplantation in MRD-based high-risk patients resulted in a significantly better 5-year EFS rate (78%, SE 8% v 16%, SE 8% in controls). Overall outcome improved significantly (5-year EFS rate 87%, 5 year survival rate 92%, and 5-year cumulative incidence of relapse rate 8%) compared with preceding Dutch Childhood Oncology Group protocols. CONCLUSION: Chemotherapy was substantially reduced safely in one-quarter of children with ALL who were selected on the basis of undetectable MRD levels, without jeopardizing the survival rate. Outcomes of patients with intermediate and high levels of MRD improved with therapy intensification. PMID- 27269952 TI - Ultrasound-guided peripheral vein cannulation. PMID- 27269951 TI - Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis. AB - PURPOSE: Related donor haploidentical hematopoietic cell transplantation (Haplo HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. MATERIALS AND METHODS: We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor-based GVHD prophylaxis. RESULTS: Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). CONCLUSION: Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD HCT, with a significantly lower risk of chronic GVHD. PMID- 27269953 TI - Cerebral edema induced by hyperammonemia: a case report. PMID- 27269948 TI - Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. AB - PURPOSE: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. PATIENTS AND METHODS: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. RESULTS: Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center-based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 * 10(-20)). The OR was higher for estrogen receptor (ER)-positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 * 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 * 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom. CONCLUSION: These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models and into guidelines for intensified screening and follow-up. PMID- 27269954 TI - Risk of transfusion-related acute lung injury after blood products transfusions. PMID- 27269955 TI - High immunoglobulin E values at admission predict mortality in ED patients with sepsis. AB - OBJECTIVES: Gamma immunoglobulin E (IgE) is associated with allergic reactions but has not been described as being activated after sepsis. This study aimed at detecting the prognostic value of plasma IgE level in sepsis progression in the emergency department (ED). METHODS: Plasma IgE and related cytokines levels were measured on enrollment, and the Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, and Mortality in Emergency Department Sepsis score were calculated on ED admission. A 28-day follow-up was performed for all patients. RESULTS: A total of 480 patients were consecutively enrolled in this study. The results revealed that nonsurvivors were in a more severe critical state, with reflected by higher IgE level and higher scoring systems (P<.001). Multivariate logistic regression analysis showed that IgE level was independent predictor of severe sepsis (odds ratio, 1.034; 95% confidence interval, 1.023-1.044; P<.001) and 28-day mortality (odds ratio, 1.038; 95% confidence interval, 1.027-1.053; P<.001). The areas under the receiver operating characteristic curve (AUC) analysis showed that IgE was a useful parameter in prognosis of severe sepsis (AUC was 0.830; cutoff value was 303.08MUg/L) and 28 day mortality (AUC was 0.700; cutoff value was 299.96MUg/L), Importantly, the AUC of combination of IgE and Mortality in Emergency Department Sepsis score performed for the most significant prognostic ability than each parameter, respectively, in this cohort (P<.001). CONCLUSIONS: The results of this study indicate that septic patients with higher IgE level present with higher risk of mortality, and a combination of IgE level with scoring systems significantly increased the predictive accuracy for severe sepsis and 28-day mortality. PMID- 27269957 TI - Pharmacogenetic Tests in Psychiatry: From Fear to Failure to Hype. PMID- 27269956 TI - Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment. AB - BACKGROUND: Methamphetamine dependence is a significant public health concern without any approved medications for treatment. We evaluated ibudilast, a nonselective phosphodiesterase inhibitor, to assess the safety and tolerability during intravenous methamphetamine administration. We conducted a randomized, double-blind, placebo-controlled, within-subjects crossover clinical trial. METHODS: Participants received ibudilast (20 mg twice daily followed by 50 mg twice daily) and placebo, with order determined by randomization, and then underwent intravenous methamphetamine challenges (15 and 30 mg). We monitored cardiovascular effects, methamphetamine pharmacokinetics, and reported adverse events. RESULTS: Ibudilast treatment had similar rates of adverse events compared with placebo, and there was no significant augmentation of cardiovascular effects of methamphetamine. Pharmacokinetic analysis revealed no clinically significant change in maximum concentration or half-life of methamphetamine with ibudilast. CONCLUSIONS: Methamphetamine administration during ibudilast treatment was well tolerated without additive cardiovascular effects or serious adverse events, providing initial safety data to pursue ibudilast's effectiveness for the treatment of methamphetamine dependence. PMID- 27269958 TI - Paliperidone Palmitate-Associated Severe Refractory Tardive Dyskinesia With Tardive Dystonia: Management and Six-Months Follow-Up. PMID- 27269959 TI - Antidepressant Use and Subclinical Measures of Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: Antidepressants are commonly prescribed medications used in primary care. The cardiovascular safety profile of antidepressant medications, in terms of subclinical atherosclerosis, is underexamined. METHODS: A total of 6814 participants in the Multi-Ethnic Study of Atherosclerosis were examined. At baseline, the mean age was 62 years with 4 race/ethnic groups represented: European Americans (38%), Hispanic Americans (23%), African Americans (28%), and Chinese Americans (11%). Antidepressants were subgrouped as serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and "other" (bupropion, nefazodone, trazodone, mirtazapine). After adjusting for potential confounders, we estimated the association between antidepressant use and the following measures of subclinical atherosclerosis: coronary artery calcium (CAC), the ankle-brachial index, and carotid intima-media thickness, both cross-sectionally and prospectively. RESULTS: A total of 324 participants were exposed to SSRIs, 88 to TCAs, 41 to SNRIs, and 123 to other antidepressants. For CAC incidence, the fully adjusted longitudinal analyses revealed no consistent associations with SSRIs (relative risk [RR], 0.99; 95% confidence interval [CI], 0.71-1.37), SNRIs (RR, 0.49; 95% CI, 0.13-1.86), TCAs (RR, 0.94; 95% CI, 0.50-1.77), other antidepressant (RR, 0.87; 95% CI, 0.73-1.03) exposure, and subclinical disease. Similar null results were obtained in the cross-sectional and longitudinal exposure to antidepressants with changes in baseline CAC greater than 0, ankle-brachial index, and carotid intima-media thickness. CONCLUSIONS: The results of the current study do not support an association between antidepressants and subclinical atherosclerosis. PMID- 27269960 TI - Learning a New Selection Rule in Visual and Frontal Cortex. AB - How do you make a decision if you do not know the rules of the game? Models of sensory decision-making suggest that choices are slow if evidence is weak, but they may only apply if the subject knows the task rules. Here, we asked how the learning of a new rule influences neuronal activity in the visual (area V1) and frontal cortex (area FEF) of monkeys. We devised a new icon-selection task. On each day, the monkeys saw 2 new icons (small pictures) and learned which one was relevant. We rewarded eye movements to a saccade target connected to the relevant icon with a curve. Neurons in visual and frontal cortex coded the monkey's choice, because the representation of the selected curve was enhanced. Learning delayed the neuronal selection signals and we uncovered the cause of this delay in V1, where learning to select the relevant icon caused an early suppression of surrounding image elements. These results demonstrate that the learning of a new rule causes a transition from fast and random decisions to a more considerate strategy that takes additional time and they reveal the contribution of visual and frontal cortex to the learning process. PMID- 27269962 TI - Newborn Brain Function Is Affected by Fetal Exposure to Maternal Serotonin Reuptake Inhibitors. AB - Recent experimental animal studies have shown that fetal exposure to serotonin reuptake inhibitors (SRIs) affects brain development. Modern recording methods and advanced computational analyses of scalp electroencephalography (EEG) have opened a possibility to study if comparable changes are also observed in the human neonatal brain. We recruited mothers using SRI during pregnancy (n = 22) and controls (n = 62). Mood and anxiety of mothers, newborn neurology, and newborn cortical function (EEG) were assessed. The EEG parameters were compared between newborns exposed to drugs versus controls, followed by comparisons of newborn EEG features with maternal psychiatric assessments. Neurological assessment showed subtle abnormalities in the SRI-exposed newborns. The computational EEG analyses disclosed a reduced interhemispheric connectivity, lower cross-frequency integration, as well as reduced frontal activity at low frequency oscillations. These effects were not related to maternal depression or anxiety. Our results suggest that antenatal serotonergic treatment might change newborn brain function in a manner compatible with the recent experimental studies. The present EEG findings suggest links at the level of neuronal activity between human studies and animal experiments. These links will also enable bidirectional translation in future studies on the neuronal mechanisms and long term neurodevelopmental effects of early SRI exposure. PMID- 27269964 TI - Addendum. PMID- 27269961 TI - Distinct Functional Groups Emerge from the Intrinsic Properties of Molecularly Identified Entorhinal Interneurons and Principal Cells. AB - Inhibitory interneurons are an important source of synaptic inputs that may contribute to network mechanisms for coding of spatial location by entorhinal cortex (EC). The intrinsic properties of inhibitory interneurons in the EC of the mouse are mostly undescribed. Intrinsic properties were recorded from known cell types, such as, stellate and pyramidal cells and 6 classes of molecularly identified interneurons (regulator of calcineurin 2, somatostatin, serotonin receptor 3a, neuropeptide Y neurogliaform (NGF), neuropeptide Y non-NGF, and vasoactive intestinal protein) in acute brain slices. We report a broad physiological diversity between and within cell classes. We also found differences in the ability to produce postinhibitory rebound spikes and in the frequency and amplitude of incoming EPSPs. To understand the source of this intrinsic variability we applied hierarchical cluster analysis to functionally classify neurons. These analyses revealed physiologically derived cell types in EC that mostly corresponded to the lines identified by biomarkers with a few unexpected and important differences. Finally, we reduced the complex multidimensional space of intrinsic properties to the most salient five that predicted the cellular biomolecular identity with 81.4% accuracy. These results provide a framework for the classification of functional subtypes of cortical neurons by their intrinsic membrane properties. PMID- 27269963 TI - Epidemiology of community-acquired pneumonia and implications for vaccination of children living in developing and newly industrialized countries: A systematic literature review. AB - This systematic review evaluated the epidemiology of community-acquired pneumonia in children <6 y of age within 90 developing and newly industrialized countries. Literature searches (1990-2011), based on MEDLINE, EMBASE, Cochrane, CAB Global Health, WHO, UNICEF, country-specific websites, conferences, health-technology assessment agencies, and the reference lists of included studies, yielded 8,734 records; 62 of 340 studies were included in this review. The highest incidence rate among included studies was 0.51 episodes/child-year, for children <5 y of age in Bangladesh. The highest prevalence was in Chinese children <6 months of age (37.88%). The main bacterial pathogens were Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae and the main viral pathogens were respiratory syncytial virus, adenovirus and rhinovirus. Community-acquired pneumonia remains associated with high rates of morbidity and mortality. Improved and efficient surveillance and documentation of the epidemiology and burden of community-acquired pneumonia across various geographical regions is warranted. PMID- 27269965 TI - Mutational scanning of the CHCHD2 gene in Han Chinese patients with Parkinson's disease and meta-analysis of the literature. AB - BACKGOUND: Building on recent evidence linking the CHCHD2 gene to both familial and sporadic Parkinson's disease (PD), we carried out a case-control study to examine possible associations between the CHCHD2 gene and PD. METHOD: We sequenced all four coding regions, exon-intron boundaries, untranslated regions and flanking regions of CHCHD2 in 30 patients with familial disease, 554 patients with sporadic disease and 594 healthy controls. All subjects were Han Chinese from western China. RESULTS: We detected the exonic variants p.Pro2Leu, p.Arg18Gln and p.Arg145Gln in six patients with sporadic PD respectively. The p.Pro2Leu variant was more frequent in patients than in controls, but the difference was not significant (OR 2.149, 95%CI 0.393 to 11.753, p = 0.366). Meta analysis of our data with studies in the literature showed that p.Pro2Leu variants were associated with sporadic PD (OR 2.51, 95%CI 1.53 to 4.11, p = 0.0002), especially in Asian populations (OR 2.92, 95%CI 1.68 to 5.07, p = 0.0001). CONCLUSION: Our results suggest that CHCHD2 exonic variants are rare among Chinese patients with PD. Meta-analysis of the literature, however, suggests that p.Pro2Leu variants are associated with sporadic disease, particularly in Asian populations. PMID- 27269966 TI - Genetic risk of Parkinson's disease in the general population. AB - INTRODUCTION: We investigated whether a risk score based on genetic risk variants for Parkinson's disease (PD) is associated with the risk and improves prediction of incident PD, and whether the risk score is associated with basic activities of daily living (BADL) in healthy individuals. METHODS: Within the population-based Rotterdam Study, we genotyped 26 independent risk variants for PD and constructed a genetic risk score in 7167 participants who were free of parkinsonism and dementia at baseline (1990 or 2000). Participants were followed for a maximum of twenty years for the onset of parkinsonism, dementia or death until January 1, 2011 (median follow-up 12.1 years). We studied the relationship between the genetic risk score and incident PD with adjustment for age, sex, smoking and parental history. In an independent sample of 2997 persons free of parkinsonism and dementia, we studied whether the PD risk score was associated with impaired BADL. RESULTS: During follow-up (median 12.1 years), 99 persons were diagnosed with incident PD. The genetic risk score was associated with incident PD (hazard ratio per standard deviation risk 1.25 [95% confidence interval = 1.02; 1.55]), but did not substantially improve prediction (change in C-statistic 0.687 [0.628; 0.745] to 0.698 [0.635; 0.760], DeltaC = 0.011 [-0.011; 0.033]). The genetic risk score was associated with a higher probability of any impairment in BADL (odds ratio = 1.11 [1.00; 1.23]). CONCLUSION: Genetic variants for PD are associated with the risk of incident PD in the general population and with impairment in daily functioning in individuals without clinical parkinsonism, but do not improve the clinical prediction of PD. However, we were probably underpowered to detect a small improvement in PD prediction. PMID- 27269967 TI - Interoception in Autism Spectrum Disorder: A review. AB - PURPOSE: This review article summarizes original scientific research published to date on interoception in individuals with Autism Spectrum Disorder (ASD). Sensory processing has been shown to be atypical in ASD, yet physiological processing and subjective experience of internal sensation processing, namely interoception, has not been reported sufficiently in research or clinical settings. BACKGROUND: There is a small but growing body of scientific research on interoception in ASD, which is relevant to understanding the behavioral and cognitive characteristics inherent in this condition, and may provide a foundation for clinical interventions such as biofeedback, pain management, and brain stimulation techniques. METHODS: A literature review of original research was performed using major scientific databases. RESULTS: Interoception, which occurs due to multisensory connections and integration of internal afferents in cortical and subcortical areas, is atypical in ASD, but the degree and directionality of this abnormality is not yet clear due to the heterogeneity of the condition. Between group interoceptive differences in individuals with and without ASD have been repeatedly demonstrated, with a slight tendency towards hyporeactivity in interoceptive awareness in individuals with ASD. SIGNIFICANCE: Multidimensional research combining neuroimaging with psychophysiological and self-report measures guided by a clear theoretical model is necessary to understand how interoceptive differences link to the behavioral and cognitive characteristics of ASD. Sensory processing models and autism theory should also be updated to incorporate these recent findings. PMID- 27269968 TI - Live liver donors' information needs: A qualitative study of practical implications for informed consent. AB - BACKGROUND: As live donor liver transplantation is increasingly used to expand the donor pool, concerns remain regarding how best to obtain live liver donors' informed consent. This study assessed donors' information preferences and their perceptions of informed consent. METHODS: Cognitive interviews were conducted with donors by telephone about how knowledge items in a new survey instrument were material to informed consent, between November 2011 and April 2012. Thematic analysis was used to analyze qualitative data until reaching saturation. RESULTS: Twenty-nine liver donors participated (85% participation). Donors commonly reported being unable to understand or retain much information disclosed during education. Donors preferred information about major donation risks, eg, death and minor risks that would likely affect their daily lives, eg, wound infection. Donors expressed less interest in information about their rights, confidentiality, or the medical procedure itself. Donors' preferences varied regarding statistical information. Many perceived the disclosure of risk information to be excessive, and rationalized risks they believed to be uncommon or not serious. Donors were disappointed by the brevity of the postdonation hospital stay. CONCLUSION: Our findings suggest that the complexity and volume of disclosed information during evaluation were difficult for donors to adequately comprehend. Donors' lack of appreciation for the seriousness of complications may undermine their ability to provide informed consent. Future research should develop effective methods of information delivery to enhance informed consent. PMID- 27269969 TI - Features of liver tissue remodeling in intestinal failure during and after weaning off parenteral nutrition. AB - BACKGROUND: Intestinal failure is associated frequently with liver injury, which persists after weaning off parenteral nutrition. We compared features of liver remodeling in intestinal failure during and after weaning off parenteral nutrition. METHODS: Liver biopsies and serum samples were obtained from 25 intestinal failure patients at a median age of 9.7 years (interquartile range: 4.6-18) and from age-matched control patients. Seven patients had been receiving parenteral nutrition for 53 months (22-160), and 18 patients had been weaned off parenteral nutrition 6.3 years (2.4-17) earlier, after having received parenteral nutrition for 10 months (3.3-34). Expression of alpha-smooth muscle actin, collagen 1, proinflammatory cytokines, growth factors, and matrix metalloproteinases (MMPs) was measured. RESULTS: Significant increases in immunohistochemical expression of alpha-smooth muscle actin and collagen 1 were observed predominantly in portal areas and were similar to increases seen in patients currently receiving parenteral nutrition and in patients weaned off parenteral nutrition. Gene and protein expressions of alpha-smooth muscle actin and collagen were interrelated. Gene expression of ACTA2, encoding alpha-smooth muscle actin, was increased only in patients who were receiving parenteral nutrition currently. Comparable upregulation of interleukin-1 (alpha and beta), epidermal growth factor, integrin-beta6, and MMP9 gene expression was observed in both patient groups, irrespective of whether they were receiving parenteral nutrition currently. Liver expression and serum levels of TIMP1 and MMP7 were increased only in the patients on parenteral nutrition currently but were not increased after weaning off parenteral nutrition. CONCLUSION: Intestinal failure is characterized by abnormal activation of hepatic myofibroblast and accumulation of collagen both during and after weaning off parenteral nutrition. Persistent transcriptional upregulation of proinflammatory and fibrogenic cytokines after weaning off parenteral nutrition suggests that factors other than parenteral nutrition may contribute to intestinal failure-associated liver disease. PMID- 27269970 TI - Mitochondrial STAT3: Powering up a potent factor. AB - The JAK-STAT3 signaling pathway is engaged by many cytokines and growth factor stimuli to control diverse biological processes including proliferation, angiogenesis, survival, immune modulation, and metabolism. For over two decades it has been accepted that STAT3-dependent biology is due to its potency as a transcription factor capable of regulating the expression of many hundreds of genes. However, recent evidence of non-canonical and non-genomic activities of STAT3 has emerged. The most exciting of these activities is its capacity to translocate into the mitochondria where it regulates the activity of the electron transport chain and the opening of the mitochondrial permeability transition pore. These have broad consequences including cell survival and the production of reactive oxygen species and ATP in both normal tissue and under pathological conditions. Despite these fascinating observations there are many key unanswered questions about the mechanism of STAT mitochondrial activity. PMID- 27269971 TI - Forecasting the Value of Podiatric Medical Care in Newly Insured Diabetic Patients During Implementation of the Affordable Care Act in California. AB - BACKGROUND: Because value-based care is critical to the Affordable Care Act success, we forecasted inpatient costs and the potential impact of podiatric medical care on savings in the diabetic population through improved care quality and decreased resource use during implementation of the health reform initiatives in California. METHODS: We forecasted enrollment of diabetic adults into Medicaid and subsidized health benefit exchange programs using the California Simulation of Insurance Markets (CalSIM) base model. Amputations and admissions per 1,000 diabetic patients and inpatient costs were based on the California Office of Statewide Health Planning and Development 2009-2011 inpatient discharge files. We evaluated cost in three categories: uncomplicated admissions, amputations during admissions, and discharges to a skilled nursing facility. Total costs and projected savings were calculated by applying the metrics and cost to the projected enrollment. RESULTS: Diabetic patients accounted for 6.6% of those newly eligible for Medicaid or health benefit exchange subsidies, with a 60.8% take-up rate. We project costs to be $24.2 million in the diabetic take-up population from 2014 to 2019. Inpatient costs were 94.3% higher when amputations occurred during the admission and 46.7% higher when discharged to a skilled nursing facility. Meanwhile, 61.0% of costs were attributed to uncomplicated admissions. Podiatric medical services saved 4.1% with a 10% reduction in admissions and amputations and an additional 1% for every 10% improvement in access to podiatric medical care. CONCLUSIONS: When implementing the Affordable Care Act, inclusion of podiatric medical services on multidisciplinary teams and in chronic-care models featuring prevention helps shift care to ambulatory settings to realize the greatest cost savings. PMID- 27269972 TI - Radiographic Measurements of the Affected and Unaffected Feet in Patients with Unilateral Hallux Limitus A Case-Control Pilot Study. AB - BACKGROUND: Controversy exists regarding the structural and functional causes of hallux limitus, including metatarsus primus elevatus, a long first metatarsal, first-ray hypermobility, the shape of the first metatarsal head, and the presence of hallux interphalangeus. Some articles have reported on the radiographic evaluation of these measurements in feet affected by hallux limitus, but no study has directly compared the affected and unaffected feet in patients with unilateral hallux limitus. This case-control pilot study aimed to establish whether any such differences exist. METHODS: Dorsoplantar and lateral weightbearing radiographs of both feet in 30 patients with unilateral hallux limitus were assessed for grade of disease, lateral intermetatarsal angle, metatarsal protrusion distance, plantar gapping at the first metatarsocuneiform joint, metatarsal head shape, and hallux abductus interphalangeus angle. Data analysis was performed using a statistical software program. RESULTS: Mean radiographic measurements for affected and unaffected feet demonstrated that metatarsus primus elevatus, a short first metatarsal, first-ray hypermobility, a flat metatarsal head shape, and hallux interphalangeus were prevalent in both feet. There was no statistically significant difference between feet for any of the radiographic parameters measured (Mann-Whitney U tests, independent-samples t tests, and Pearson chi(2) tests: P > .05). CONCLUSIONS: No significant differences exist in the presence of the structural risk factors examined between affected and unaffected feet in patients with unilateral hallux limitus. The influence of other intrinsic factors, including footedness and family history, should be investigated further. PMID- 27269973 TI - Surgical Management of Gout in the Foot and Ankle A Systematic Review. AB - BACKGROUND: The surgical management of tophaceous gout has been well documented in the literature, including its effect on foot pain and disability. To date, there have been no systematic reviews assessing the quality of the literature relating to the operative management of tophaceous gout and the outcomes in the foot and ankle. METHODS: The following electronic databases were searched (1980 2014): Allied and Complementary Medicine, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Scopus, and the Cochrane Library. The articles identified were published in English and included adult participants (age >=18 years) with diagnosed gout and surgical intervention to the foot and ankle. The Downs and Black Quality Index was modified to assess the quality of the articles being reviewed. RESULTS: Six articles were reviewed and were of moderate quality (mean quality score of 71%). Surgical management was conducted on men (88%) with a mean age of 52 years. There was wide variation in the types of surgical procedures performed, with 28% of studies reporting surgery to the first metatarsophalangeal joint. Most studies were retrospective. A wide range of outcome measures were reported: foot pain, function, preoperative and postoperative activity levels, monitoring of uric acid levels, and patient satisfaction after surgery. CONCLUSIONS: The review demonstrated a limited number of good-quality studies. Several surgical procedures for the foot and ankle in people with chronic tophaceous gout were reported. Future studies should include prospective observational studies using validated and reliable patient-reported outcome measures. PMID- 27269974 TI - Range of Motion and Plantar Pressure Evaluation for the Effects of Self-Care Foot Exercises on Diabetic Patients with and Without Neuropathy. AB - BACKGROUND: We aimed to investigate whether a home exercise for self-care program that consists of range of motion (ROM), stretching, and strengthening exercises could improve ROM for foot joints and plantar pressure distribution during walking in diabetic patients to prevent diabetic foot complications. METHODS: Seventy-six diabetic patients were recruited (38 with neuropathy and 38 without neuropathy). Neuropathy and nonneuropathy groups were randomly divided into a home exercise group (n = 19) and a control group (n = 19). Exercise groups performed their own respective training programs for 4 weeks, whereas no training was done in the control group. Total contact area and plantar pressure under six foot areas before and after the exercise program were measured. Ankle and first metatarsophalangeal joint ROM were measured before and after the exercise program. RESULTS: In the exercise group, there were significant improvements in ROM for the ankle and first metatarsophalangeal joints (P < .001); static pedobarographic values showed significant reduction in right forefoot-medial pressure (P = .010); and significant decreases were seen in dynamic pedobarographic values of peak plantar pressure at the left forefoot medial (P = .007), right forefoot lateral (P = .018), left midfoot (P < .001), and right hindfoot (P = .021) after exercise. No significant positive or negative correlation was found between the neuropathy and nonneuropathy groups (P > .05). CONCLUSIONS: A home exercise program could be an effective preventive method for improving ROM for foot joints and plantar pressure distribution in diabetic patients independent of the presence of neuropathy. PMID- 27269975 TI - Foot Pressure Pattern During Walking in Individuals with Anterior Cruciate Ligament Injury. AB - BACKGROUND: We evaluated foot pressure distribution during walking in individuals with anterior cruciate ligament (ACL) injury. METHODS: Our study included 24 ACL deficient patients and 22 healthy young adults as controls. The former group was divided into the dominant-side ACL-deficient group (n = 17) and the nondominant side ACL-deficient group (n = 7). The following parameters were calculated from the path of the center of pressure (COP) on a foot pressure distribution system: percentage of COP (%COP; the ratio of anteroposterior COP path length to foot length), percentage of COP locus area (%CLA; the ratio of the area encompassed by the COP path and a line between the start and end points of the COP path to foot area), and the value of maximum amplitude of COP (MACOP; the maximum perpendicular length from the COP path to a line between the start and end points of the COP). RESULTS: In the nondominant-side ACL-deficient group, %COP (P = .026), %CLA (P = .001), and MACOP (P =.012) on the injured side were significantly lower than those in the nondominant leg side of the control group. No significant differences were found between the dominant-side ACL-deficient group and the control group. CONCLUSIONS: Shortening of the COP trace in the nondominant-side ACL-deficient group may be associated with knee flexion during walking at heel contact. Because the parameters used herein can be obtained easily, repetitively, and quantitatively, they should be used in evaluating the gait of patients with ACL-deficient knees. PMID- 27269976 TI - Reliability and Validity of the Footprint Assessment Method Using Photoshop CS5 Software in Young People with Down Syndrome. AB - BACKGROUND: People with Down syndrome present skeletal abnormalities in their feet that can be analyzed by commonly used gold standard indices (the Hernandez Corvo index, the Chippaux-Smirak index, the Staheli arch index, and the Clarke angle) based on footprint measurements. The use of Photoshop CS5 software (Adobe Systems Software Ireland Ltd, Dublin, Ireland) to measure footprints has been validated in the general population. The present study aimed to assess the reliability and validity of this footprint assessment technique in the population with Down syndrome. METHODS: Using optical podography and photography, 44 footprints from 22 patients with Down syndrome (11 men [mean +/- SD age, 23.82 +/ 3.12 years] and 11 women [mean +/- SD age, 24.82 +/- 6.81 years]) were recorded in a static bipedal standing position. A blinded observer performed the measurements using a validated manual method three times during the 4-month study, with 2 months between measurements. Test-retest was used to check the reliability of the Photoshop CS5 software measurements. Validity and reliability were obtained by intraclass correlation coefficient (ICC). RESULTS: The reliability test for all of the indices showed very good values for the Photoshop CS5 method (ICC, 0.982-0.995). Validity testing also found no differences between the techniques (ICC, 0.988-0.999). CONCLUSIONS: The Photoshop CS5 software method is reliable and valid for the study of footprints in young people with Down syndrome. PMID- 27269977 TI - Relationship Between Academic Performance and Student Self-Assessment of Clinical Performance in the College of Podiatric Medicine and Surgery. AB - BACKGROUND: Student self-assessment is viewed as an important tool in medical education. We sought to identify the relationship between student academic performance and third-year clinical performance self-assessment. No such study exists in podiatric medical education. METHODS: Third-year podiatric medical students from the classes of 2012 through 2014 completed a self-assessment of their performance for each of five broad clinical podiatric medical domains (Professionalism, Medicine, Radiology, Surgery, and Biomechanics/Orthopedics). The assessment was completed after students finished the first 12 weeks of their third-year clinical rotations (PRE) and a second time at the conclusion of the third year (POST). The mean self-assessment score for PRE and POST surveys for all combined domains was determined for each student. This mean was compared with the student's 3-year cumulative grade point average (GPA). Students' clinical experiences for the year were essentially identical. RESULTS: No statistically significant correlation was identified between cumulative GPA and the PRE and POST clinical self-assessments or with the change between PRE and POST assessments based on the Pearson correlation test for each class separately or on the pooled data. CONCLUSIONS: Published studies in allopathic medical education have shown that students with lower GPAs tend to rate their clinical performance higher in initial clinical performance self-assessment. Our results show that student academic performance was not correlated with clinical performance self assessment. These findings may be due to the explicit description of successful clinical competency completion, the orientation students receive before the start of clinical training, and the continuous feedback received from clinical preceptors. PMID- 27269978 TI - Talar Osteochondroma Fracture Presenting as Posterior Ankle Impingement. AB - Osteochondromas are the most common benign bone tumors. They are usually asymptomatic and found incidentally. When symptomatic, the symptoms are usually due to its location and size. Fracture of an osteochondroma presenting as posterior ankle impingement is a rare condition. We describe a 22-year-old man with solitary exostosis who presented with a posterior ankle mass and posterior ankle impingement with 2 years of follow-up. Surgical intervention was the treatment of choice in this patient, and histologic examination revealed a benign osteochondroma. Osteochondromas found in the posterior aspect of the talus can be complicated by fracture due to persistent motion of the ankle. Talar osteochondroma should be included in the differential diagnosis of posterior ankle impingement causes. Posterior talar osteochondromas, especially when a stalk is present, should be treated surgically before it is more complicated by a fracture and posterior ankle impingement. PMID- 27269979 TI - Neurectomy for Bilateral Morton's Neuroma A Case Report of a Male Patient. AB - Morton's neuroma is a common condition that mainly affects middle-aged women, and many articles have addressed the surgical treatment of this condition. Previous reports have described bilateral neuroma excision in women but not in men. We report a rare case of bilateral neuromas in a male patient treated with simultaneous neurectomy. PMID- 27269980 TI - Plantar Molluscum Contagiosum in an Adult Patient. AB - Molluscum contagiosum is a viral infection of the skin. It may occur anywhere on the skin surface but is most common in skinfolds, on the face, and in the genital region. Atypical presentations are usually seen in conditions with altered immunity, but they may occur in immunocompetent patients as well. We present a case of an unusual presentation of molluscum contagiosum lesions (multiple normal and one giant) on the plantar area of the foot in an adult. PMID- 27269981 TI - Solitary Eccrine Syringofibroadenoma and Successful Treatment with Cryotherapy. AB - First described in 1963, eccrine syringofibroadenoma (ESFA) is a rare benign tumor that proliferates with differentiation toward ductal eccrine structures. There are many clinical presentations, including plaques, papules, verrucous plaques, keratotic tumors, and solitary tumors. The age of onset varies, with presentation between 16 and 80 years; however, solitary lesions are seen most commonly in the seventh and eighth decades. Here, we present the case of a 72 year-old woman referred to our outpatient clinic with a nodule on her leg. The histopathology result was ESFA. The lesion regressed after six cryotherapy sessions. Physicians should consider the possibility of ESFA and must remember its malignant potential in elderly patients. PMID- 27269982 TI - Letter to the Editor. PMID- 27269983 TI - Acceptance Address: APMA House of Delegates, Washington, DC, March 20, 2016. PMID- 27269988 TI - Ligand-Enabled, Copper-Catalyzed Regio- and Stereoselective Synthesis of Trialkylsubstituted Alkenylboronates from Unactivated Internal Alkynes. AB - We report the first copper-catalyzed regio- and stereoselective borylalkylation of dialkylsubstituted internal alkynes with bis(pinacolato)diboron and alkyl halides. A catalytically generated borylcopper species containing a novel pi accepting N-heterocyclic carbene ligand chemoselectively reacted with unactivated internal alkynes over alkyl halides. The intermediate alkenylcopper species subsequently reacted with alkyl halides, affording the desired products. The copper catalyst differentiated steric demands between the two aliphatic substituents on the C=C triple bond of the alkyne substrates to exhibit high regioselectivity from a wide range of alkyne/alkyl halide combinations. This method is useful for the straightforward synthesis of trialkylsubstituted alkenylboronates, i.e., versatile precursors for tetrasubstituted alkenes containing three or four different alkylsubstituents, which are difficult to synthesize by other methods. PMID- 27269990 TI - Interatrial Block to Guide the Thromboembolic Prevention Strategy: Should It be the Next Step? PMID- 27269989 TI - Comparison of Standard Catheters Versus Radial Artery-Specific Catheter in Patients Who Underwent Coronary Angiography Through Transradial Access. AB - In this prospective, randomized controlled study, we aim to compare the performance outcomes of standard catheters with the radial artery-specific catheter. Over the past decade, transradial cardiac catheterization has gained widespread popularity because of its low complication rates compared with transfemoral access. Operators have the choice of using either standard catheters (used for both transfemoral and transradial approach, with need for separate catheter use for either right or left coronary artery engagement) or a dedicated radial artery catheter, which is specifically designed to engage both coronary arteries through radial artery access. A total of 110 consecutive patients who underwent coronary angiography at our institution from March 2015 to April 2015 were prospectively randomized to either radial artery-specific Tiger catheter (5Fr; Terumo Interventional Systems, Somerset, New Jersey) versus standard Judkins left and right catheters (5Fr R4, L4; Cordis Corporation, Miami, Florida). The end points of the study included fluoroscopy time, dose-area product, contrast volume used, and total procedure time for the coronary angiography. A total of 57 patients (52%) were randomized to radial artery specific catheter and 53 (48%) to the standard catheter. Tiger catheter was associated with significantly lower fluoroscopy time (184 +/- 91 vs 238 +/- 131 seconds, p = 0.015), which was statistically significant. Other outcome measures such as dose-area product (2,882.4 +/- 1,471.2 vs 3,524.6 +/- 2,111.7 Gy.cm(2), p = 0.07), total contrast volume (48.1 +/- 16.1 vs 53.4 +/- 18.5 ml, p = 0.114), and total procedure time (337 +/- 382 vs 434 +/- 137 seconds, p = 0.085) were also lower in single-catheter group, but it did not reach statistical significance. A total of 8 patients (14%) were crossed over from radial-specific catheter arm to standard catheter arm because of substandard image quality and difficulty in coronary engagement. Six patients had to be switched to femoral access (3 in each group) secondary to radial artery spasm. In conclusion, the radial artery-specific catheter was shown to have significantly lower fluoroscopy times but higher failure rates compared with the standard catheters. PMID- 27269991 TI - Novel strategies for the treatment of grass pollen-induced allergic rhinitis. AB - INTRODUCTION: Allergic rhinitis (AR) affects over 20% of the population of Europe and the United States. Allergen immunotherapy (AIT) is currently the only form of treatment that affects symptoms and modifies the progression of disease. Established forms of AIT include subcutaneous (SCIT) and sublingual (SLIT) immunotherapy and are widely effective, yet only 2-9% of eligible patients undergo therapy, likely due to the long duration of treatment. As a result, novel, faster forms of AIT are currently under development. AREAS COVERED: This article provides an overview of AR and summarises the efficacy and mechanisms of established forms of AIT, highlighting the current drawbacks. We discuss novel strategies of AIT that have been developed in an attempt to tackle these limitations, including epicutaneous, intradermal and intralymphatic immunotherapy (ILIT), focusing on ILIT, the treatment that has been most comprehensively assessed. EXPERT OPINION: Current strategies to treat AR suffer from a poor safety profile and, importantly, lack of adherence. ILIT is a faster and safer form of AIT, with a treatment regime of only 12 weeks. Further validation is required, but ILIT, with its short and comparatively inexpensive protocol, has the potential to offer disease-modifying therapy to a larger number of patients. PMID- 27269992 TI - Trace element concentrations in the moss Hypnum cupressiforme growing in a presumably unpolluted area. AB - In this study we determined the concentrations of As, Cd, Hg, Ni and Pb in samples of the moss Hypnum cupressiforme collected during 5 different sampling surveys (2006-2014) in a presumably unpolluted area in northern Spain (25 sampling sites). We then applied factor analysis (FA) to the data to explore the factors underlying the spatial and temporal variability in the concentrations. The percentage of variance explained by the FA ranged between 34 and 98%, and was usually higher than 70%. The FA yielded 5 factors that explained the variance in the concentrations of Cd, As, Hg and Pb in all sampling surveys and also a single factor that explained the variance in Hg and Pb concentrations in 2006. Although the lack of obvious sources of pollution in the study region (at least for the elements considered) suggests that most elements (except perhaps Ni) probably originated from long-range atmospheric transport, this would not explain the results of the FA. We suggest that rather than being due to the origin of the pollutants (as frequently assumed), the spatio-temporal variability in the concentrations of these elements is probably determined by a series of other factors: the physicochemical characteristics of the pollutants and of the moss binding surfaces, physiological processes (e.g. moss growth), and the characteristics of the sampling sites (e.g. vegetation cover, elevation, slope, aspect). We therefore conclude that the assumption that variations in element concentrations in moss tissues are due to the origin of the pollutants is an oversimplification that leads to erroneous interpretation of the results of biomonitoring studies with terrestrial mosses. PMID- 27269993 TI - Persulfate activation during exertion of total oxidant demand. AB - Total oxidant demand (TOD) is a parameter that is often measured during in situ chemical oxidation (ISCO) treatability studies. The importance of TOD is based on the concept that the oxidant demand created by soil organic matter and other reduced species must be overcome before contaminant oxidation can proceed. TOD testing was originally designed for permanganate ISCO, but has also recently been applied to activated persulfate ISCO. Recent studies have documented that phenoxides activate persulfate; because soil organic matter is rich in phenolic moieties, it may activate persulfate rather than simply exerting TOD. Therefore, the generation of reactive oxygen species was investigated in three soil horizons of varied soil organic carbon content over 5-day TOD testing. Hydroxyl radical may have been generated during TOD exertion, but was likely scavenged by soil organic matter. A high flux of reductants + nucleophiles (e.g. alkyl radicals + superoxide) was generated as TOD was exerted, resulting in the rapid destruction of the probe compound hexachloroethane and the common groundwater contaminant trichloroethylene (TCE). The results of this research document that, unlike permanganate TOD, contaminant destruction does occur as TOD is exerted in persulfate ISCO systems and is promoted by the activation of persulfate by soil organic matter. Future treatability studies for persulfate ISCO should consider contaminant destruction as TOD is exerted, and the potential for persulfate activation by soil organic matter. PMID- 27269995 TI - Editorial. PMID- 27269994 TI - The mixture toxicity of environmental contaminants containing sulfonamides and other antibiotics in Escherichia coli: Differences in both the special target proteins of individual chemicals and their effective combined concentration. AB - Organisms in the environment are exposed to mixtures of multiple contaminants, leading to serious environmental harm. These mixtures pose an ecological risk and have attracted an increasing amount of attention; however there has been little in-depth research the toxicity of mixtures, such as antibiotics. To determine how different mixtures of antibiotics affect organisms, the individual and mixture toxicity of sulfonamides and several antibiotics were determined using Escherichia coli as a target organism in our study. The results show that additive effects occur between sulfonamides and quinolones or with a portion of beta-lactams, synergistic effects appear between sulfonamides and their potentiators or cefotaxime sodium, and antagonistic effects arise between sulfonamides and tetracyclines or penicillin V potassium salt. In addition, the toxicity mechanism of binary mixtures is further discussed and the results reveal that the joint effect differences depend not only the target proteins of individual chemicals but also on their effective combined concentration based on the approach of Quantitative Structure Activity Relationships (QSARs) and molecular docking. This study introduces the concept of the "effective concentration" to provide insight into understanding the mechanism of binary mixtures, which will be beneficial for evaluating the ecological risk of antibiotics. PMID- 27269996 TI - Introducing the individual Teamwork Observation and Feedback Tool (iTOFT): Development and description of a new interprofessional teamwork measure. AB - The individual Teamwork Observation and Feedback Tool (iTOFT) was devised by a consortium of seven universities in recognition of the need for a means of observing and giving feedback to individual learners undertaking an interprofessional teamwork task. It was developed through a literature review of the existing teamwork assessment tools, a discussion of accreditation standards for the health professions, Delphi consultation and field-testing with an emphasis on its feasibility and acceptability for formative assessment. There are two versions: the Basic tool is for use with students who have little clinical teamwork experience and lists 11 observable behaviours under two headings: 'shared decision making' and 'working in a team'. The Advanced version is for senior students and junior health professionals and has 10 observable behaviours under four headings: 'shared decision making', 'working in a team', 'leadership', and 'patient safety'. Both versions include a comprehensive scale and item descriptors. Further testing is required to focus on its validity and educational impact. PMID- 27269997 TI - When the social discourse on violation behaviours is challenged by the perception of everyday life experiences: Effects of non-accident experiences on offending attitudes and habits. AB - The aim of this article is to introduce the concept of the Non-Accident Experience (NAE) with regard to violations of traffic safety regulations. An NAE refers to the fact of not having been involved in an accident following the adoption of a behaviour socially recognised as promoting its occurrence. We hypothesise that this type of experiences has a strong effect on attitudes (valence and strength) and habits with regard to traffic offences such as speeding and drink-drive. An empirical study was conducted to test the relevance of this set of hypotheses. 543 French drivers participated to a survey designed to measure all these theoretical constructs. As expected, the results showed that the more frequently NAEs were experienced the more individuals had a favourable and weak (less certain, less important, more ambivalent) attitude towards violations, as well as strong habits. In addition, the more numerous NAEs experienced by others were perceived to be, the more ambivalent was the attitude. The discussion firstly concerns the methodological limitations of this study (e.g. use of cross-sectional design) as well as the integration of this concept into current research, especially in relation to the attitude strength concept and the theory of planned behaviour. Then, we discuss its practical implications (use of the experience based analysis technique, with consideration of both accident and non-accident experiences). PMID- 27269998 TI - Social costs of road crashes: An international analysis. AB - This paper provides an international overview of the most recent estimates of the social costs of road crashes: total costs, value per casualty and breakdown in cost components. The analysis is based on publications about the national costs of road crashes of 17 countries, of which ten high income countries (HICs) and seven low and middle income countries (LMICs). Costs are expressed as a proportion of the gross domestic product (GDP). Differences between countries are described and explained. These are partly a consequence of differences in the road safety level, but there are also methodological explanations. Countries may or may not correct for underreporting of road crashes, they may or may not use the internationally recommended willingness to pay (WTP)-method for estimating human costs, and there are methodological differences regarding the calculation of some other cost components. The analysis shows that the social costs of road crashes in HICs range from 0.5% to 6.0% of the GDP with an average of 2.7%. Excluding countries that do not use a WTP- method for estimating human costs and countries that do not correct for underreporting, results in average costs of 3.3% of GDP. For LMICs that do correct for underreporting the share in GDP ranges from 1.1% to 2.9%. However, none of the LMICs included has performed a WTP study of the human costs. A major part of the costs is related to injuries: an average share of 50% for both HICs and LMICs. The average share of fatalities in the costs is 23% and 30% respectively. Prevention of injuries is thus important to bring down the socio-economic burden of road crashes. The paper shows that there are methodological differences between countries regarding cost components that are taken into account and regarding the methods used to estimate specific cost components. In order to be able to make sound comparisons of the costs of road crashes across countries, (further) harmonization of cost studies is recommended. This can be achieved by updating and improving international guidelines and applying them in future cost studies. The information regarding some cost components, particularly human costs and property damage, is poor and more research into these cost components is recommended. PMID- 27269999 TI - Strategies for improving safety performance in construction firms. AB - Over the years many prevention management practices have been implemented to prevent and mitigate accidents at the construction site. However, there is little evidence of the effectiveness of individual or combined practices used by companies to manage occupational health and safety issues. The authors selected a sample of 1180 construction firms and 221 individual practices applied in these companies to analyze their effectiveness reducing injury rates over a period of four years in Chile. Different methods were used to study this massive database including: visual analyses of graphical information, statistical analyses and classification techniques. Results showed that practices related to safety incentives and rewards are the most effective from the accident rate viewpoint, even though they are seldom used by companies; on the other hand, practices related to accidents and incidents investigation had a slight negative impact on the accident rate because they are frequently used as a reactive measure. In general, the higher the percentage of prevention practices implemented in a strategy, the lower the accident rate. However, the analysis of the combined effect of prevention practices indicated that the choice of the right combination of practices was more important than just the number of practices implemented. PMID- 27270004 TI - Single-Molecule Reaction Chemistry in Patterned Nanowells. AB - A new approach to synthetic chemistry is performed in ultraminiaturized, nanofabricated reaction chambers. Using lithographically defined nanowells, we achieve single-point covalent chemistry on hundreds of individual carbon nanotube transistors, providing robust statistics and unprecedented spatial resolution in adduct position. Each device acts as a sensor to detect, in real-time and through quantized changes in conductance, single-point functionalization of the nanotube as well as consecutive chemical reactions, molecular interactions, and molecular conformational changes occurring on the resulting single-molecule probe. In particular, we use a set of sequential bioconjugation reactions to tether a single-strand of DNA to the device and record its repeated, reversible folding into a G-quadruplex structure. The stable covalent tether allows us to measure the same molecule in different solutions, revealing the characteristic increased stability of the G-quadruplex structure in the presence of potassium ions (K(+)) versus sodium ions (Na(+)). Nanowell-confined reaction chemistry on carbon nanotube devices offers a versatile method to isolate and monitor individual molecules during successive chemical reactions over an extended period of time. PMID- 27270028 TI - Metastatic solid tumors to the jaw and oral soft tissue: A retrospective clinical analysis of 44 patients from a single institution. AB - PURPOSE: Metastatic solid tumors to the oral cavity are rare, frequently indicative of an end-stage disease process, and associated with poor survival rates. We performed a 20-year retrospective clinical analysis of our institution's cases of solid metastases to the oral cavity, and investigated these patients' clinical outcomes. MATERIAL AND METHODS: A retrospective study of patients with metastatic solid tumors to the oral cavity over a 20-year period (October 1996 to September 2015) was conducted at Memorial Sloan Kettering Cancer Center. Patients were selected if they had a histopathologically confirmed diagnosis. Demographic, pathologic, and clinical information were reviewed to identify patient outcomes. RESULTS: A total of 44 patients with metastatic non melanocytic non-hematopoietic tumor to the oral cavity were identified: 24 males and 20 females (39 adults and 5 children) with a mean age of 54.3 years. In all, 24 cases involved the jaw and 20 cases involved the oral soft tissue. Eight patients (18.2%) had oral cavity metastases as the first indication of an occult malignancy. In adult patients, the common primary sites were the lungs (n = 9, 20%), kidney (n = 7, 16%), breast (n = 5, 11%), and colon (n = 4, 9%); and in pediatric patients the adrenal gland (3/5) was the most common site. Of the adult patients, 33 (84.6%) died of disease. From the time of metastasis diagnosis, patients with jaw metastases had a median and mean survival of 12 months and 27.7 months, respectively. In comparison, patients with oral soft tissue metastases had a median survival time of 5 months, and mean of 8 months. One pediatric patient (20%) died of disease 8 months after metastasis diagnosis. CONCLUSION: Metastatic solid tumors to the oral cavity can be the first sign of a malignancy. Pediatric patients with oral cavity metastases have a better prognosis compared to adult patients. In this series, adults with oral soft tissue involvement had shorter survival times compared to patients with jaw involvement. PMID- 27270029 TI - Incorporation of Phosphonate into Benzonaphthyridine Toll-like Receptor 7 Agonists for Adsorption to Aluminum Hydroxide. AB - Small molecule Toll-like receptor 7 (TLR7) agonists have been used as vaccine adjuvants by enhancing innate immune activation to afford better adaptive response. Localized TLR7 agonists without systemic exposure can afford good adjuvanticity, suggesting peripheral innate activation (non-antigen-specific) is not required for immune priming. To enhance colocalization of antigen and adjuvant, benzonaphthyridine (BZN) TLR7 agonists are chemically modified with phosphonates to allow adsorption onto aluminum hydroxide (alum), a formulation commonly used in vaccines for antigen stabilization and injection site deposition. The adsorption process is facilitated by enhancing aqueous solubility of BZN analogs to avoid physical mixture of two insoluble particulates. These BZN phosphonates are highly adsorbed onto alum, which significantly reduced systemic exposure and increased local retention post injection. This report demonstrates a novel approach in vaccine adjuvant design using phosphonate modification to afford adsorption of small molecule immune potentiator (SMIP) onto alum, thereby enhancing co-delivery with antigen. PMID- 27270030 TI - Syndecan-2 enhances E-cadherin shedding and fibroblast-like morphological changes by inducing MMP-7 expression in colon cancer cells. AB - E-cadherin plays a mechanical role in mediating cell-cell interactions and maintaining epithelial tissue integrity, and the loss of E-cadherin function has been implicated in cancer progression and metastasis. Syndecan-2, a cell-surface heparan sulfate proteoglycan, is upregulated during the development of colon cancer. Here, we assessed the functional relationship between E-cadherin and syndecan-2. We found that stable overexpression of syndecan-2 in a human colorectal adenocarcinoma cell line (HT29) enhanced the proteolytic shedding of E cadherin to conditioned-media. Either knockdown of matrix metalloproteinase 7 (MMP-7) or inhibition of MMP-7 activity using GM6001 significantly reduced the extracellular shedding of E-cadherin, suggesting that syndecan-2 mediates E cadherin shedding via MMP-7. Consistent with this notion, enhancement of MMP-7 expression by interleukin-1alpha treatment increased the shedding of E-cadherin. Conversely, the specific reduction of either syndecan-2 or MMP-7 reduced the shedding of E-cadherin. HT29 cells overexpressing syndecan-2 showed significantly lower cell-surface expression of E-cadherin, decreased cell-cell contact, a more fibroblastic cell morphology, and increased expression levels of ZEB-1. Taken together, these data suggest that syndecan-2 induces extracellular shedding of E cadherin and supports the acquisition of a fibroblast-like morphology by regulating MMP-7 expression in a colon cancer cell line. PMID- 27270031 TI - Increased fatty acid synthesis inhibits nitrogen starvation-induced autophagy in lipid droplet-deficient yeast. AB - Macroautophagy is a degradative pathway whereby cells encapsulate and degrade cytoplasmic material within endogenously-built membranes. Previous studies have suggested that autophagosome membranes originate from lipid droplets. However, it was recently shown that rapamycin could induce autophagy in cells lacking these organelles. Here we show that lipid droplet-deprived cells are unable to perform autophagy in response to nitrogen-starvation because of an accelerated lipid synthesis that is not observed with rapamycin. Using cerulenin, a potent inhibitor of fatty acid synthase, and exogenous addition of palmitic acid we could restore nitrogen-starvation induced autophagy in the absence of lipid droplets. PMID- 27270032 TI - Tetrandrine induces lipid accumulation through blockade of autophagy in a hepatic stellate cell line. AB - Macroautophagy, or autophagy, is a cellular response in which unnecessary cytoplasmic components, including lipids and organelles, are self-degraded. Recent studies closely related autophagy to activation of hepatic stellate cells (HSCs), a process critical in the pathogenesis of liver fibrosis. During HSC activation, cytoplasmic lipid droplets (LDs) are degraded as autophagic cargo, and then cells express fibrogenic genes. Thus, inhibition of autophagy in HSCs is a potential therapeutic approach for attenuating liver fibrosis. We found that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra, induced lipid accumulation, a phenotype associated with quiescent HSCs, through blockade of autophagy in the rat-derived HSC line HSC-T6. Tetrandrine inhibited autophagic flux without affecting lysosomal function. A phenotypic comparison using siRNA knockdown suggested that tetrandrine may target regulators, involved in fusion between autophagosomes and lysosomes (e.g., syntaxin 17). Moreover, perilipin 1, an LD-coated protein, co-localized specifically with LC3, a marker protein for autophagosomes, in tetrandrine-treated HSC-T6 cells. This suggests a potential role for perilipin 1 in autophagy-mediated LD degradation in HSCs. Our results identified tetrandrine as a potential tool for prevention and treatment of HSC activation. PMID- 27270034 TI - DePFth Perception in Clathrin-Mediated Endocytosis. AB - The earliest stages of clathrin-coated structure (CCS) assembly involve the recruitment and stabilization of clathrin-binding adaptor proteins and the clathrin coat. In this issue of Developmental Cell, Ma et al. (2016) now identify transient protein interactions that form the basis of AP-2 adaptor complex stabilization, key to initiating CCS formation. PMID- 27270033 TI - Multiplexed Western Blotting Using Microchip Electrophoresis. AB - Western blotting is a commonly used protein assay that combines the selectivity of electrophoretic separation and immunoassay. The technique is limited by long time, manual operation with mediocre reproducibility, and large sample consumption, typically 10-20 MUg per assay. Western blots are also usually used to measure only one protein per assay with an additional housekeeping protein for normalization. Measurement of multiple proteins is possible; however, it requires stripping membranes of antibody and then reprobing with a second antibody. Miniaturized alternatives to Western blot based on microfluidic or capillary electrophoresis have been developed that enable higher-throughput, automation, and greater mass sensitivity. In one approach, proteins are separated by electrophoresis on a microchip that is dragged along a polyvinylidene fluoride membrane so that as proteins exit the chip they are captured on the membrane for immunoassay. In this work, we improve this method to allow multiplexed protein detection. Multiple injections made from the same sample can be deposited in separate tracks so that each is probed with a different antibody. To further enhance multiplexing capability, the electrophoresis channel dimensions were optimized for resolution while keeping separation and blotting times to less than 8 min. Using a 15 MUm deep * 50 MUm wide * 8.6 cm long channel, it is possible to achieve baseline resolution of proteins that differ by 5% in molecular weight, e.g., ERK1 (44 kDa) from ERK2 (42 kDa). This resolution allows similar proteins detected by cross-reactive antibodies in a single track. We demonstrate detection of 11 proteins from 9 injections from a single Jurkat cell lysate sample consisting of 400 ng of total protein using this procedure. Thus, multiplexed Western blots are possible without cumbersome stripping and reprobing steps. PMID- 27270035 TI - The KAT's Out of the Bag: Histone Acetylation Promotes Centromere Assembly. AB - Heterochromatin is incompatible with centromeric chromatin assembly and propagation. In this issue of Developmental Cell, Ohzeki et al. (2016) reveal that a critical role of the Mis18 complex is to transiently recruit the lysine acetyltransferase KAT7 to centromeres to facilitate the removal of H3K9me3 and the deposition of CENP-A. PMID- 27270036 TI - Custom-Made Quorum Sensing for a Eukaryote. AB - Quorum-sensing systems, common in prokaryotes, enable bacteria to coordinately regulate behavior with population density. Reporting recently in Cell Host & Microbe, Homer et al. (2016) characterize an elegant eukaryotic quorum-sensing pathway in the human pathogenic fungus Cryptococcus neoformans. PMID- 27270037 TI - Size Regulation: Big Insights from Little Cells. AB - Reporting in Cell, Harris and Theriot (2016) use modeling and quantitative imaging to analyze bacterial cell growth and division. By manipulating surface and volume growth rates, the authors provide insight into bacterial cell size regulation and propose that a threshold level of unincorporated cell wall material specifies when cells divide. PMID- 27270038 TI - Cilia Train Spotting. AB - Cilium formation depends on intraflagellar transport trains that move bidirectionally along ciliary microtubules. Reporting in Science, Stepanek and Pigino (2016) employ correlative light and electron microscopy in algae to determine the ultrastructure of anterograde and retrograde trains and discover that these trains avoid collision by running on B- and A-tubules, respectively. PMID- 27270039 TI - Small but Mighty: Nanoparticles Probe Cellular Signaling Pathways. AB - Mechanical forces play key roles in regulating cellular pathways but are challenging to study using standard biological approaches. In a recent issue of Cell, Seo et al. (2016) present a platform for in vivo single-molecule manipulation, using magnetoplasmonic nanoparticles capable of imaging, localizing, and force-loading receptor proteins at high spatiotemporal resolution. PMID- 27270040 TI - KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1 Mediated Centromere Inactivation. AB - Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long alpha-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads into adjacent chromatin and represses gene expression, and it can antagonize centromere function or CENP-A assembly. Here, we demonstrate an interaction between CENP-A assembly factor M18BP1 and acetyltransferase KAT7/HBO1/MYST2. Knocking out KAT7 in HeLa cells reduced centromeric CENP-A assembly. Mitotic chromosome misalignment and micronuclei formation increased in the knockout cells and were enhanced when the histone H3-K9 trimethylase Suv39h1 was overproduced. Tethering KAT7 to an ectopic alphoid DNA integration site removed heterochromatic H3K9me3 modification and was sufficient to stimulate new CENP-A or histone H3.3 assembly. Thus, KAT7-containing acetyltransferases associating with the Mis18 complex provides competence for histone turnover/exchange activity on alphoid DNA and prevents Suv39h1-mediated heterochromatin invasion into centromeres. PMID- 27270042 TI - Annexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport. AB - Membrane contact sites between the ER and multivesicular endosomes/bodies (MVBs) play important roles in endosome positioning and fission and in neurite outgrowth. ER-MVB contacts additionally function in epidermal growth factor receptor (EGFR) tyrosine kinase downregulation by providing sites where the ER localized phosphatase, PTP1B, interacts with endocytosed EGFR before the receptor is sorted onto intraluminal vesicles (ILVs). Here we show that these contacts are tethered by annexin A1 and its Ca(2+)-dependent ligand, S100A11, and form a subpopulation of differentially regulated contact sites between the ER and endocytic organelles. Annexin A1-regulated contacts function in the transfer of ER-derived cholesterol to the MVB when low-density lipoprotein-cholesterol in endosomes is low. This sterol traffic depends on interaction between ER-localized VAP and endosomal oxysterol-binding protein ORP1L, and is required for the formation of ILVs within the MVB and thus for the spatial regulation of EGFR signaling. PMID- 27270043 TI - Aiming for cure in HBV and HDV infection. AB - Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide. Currently available antiviral treatment options for chronic hepatitis B include pegylated interferon alpha2a (PegIFN) or nucleos(t)ide analogues (NAs). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of sustained on-treatment response to therapy. The advantages of PegIFN include a finite course of treatment, the absence of drug resistance, and an opportunity to obtain a durable post-treatment response to therapy. Furthermore, PegIFN is the only approved agent known to be active against hepatitis D virus (HDV). The use of these two antiviral agents with different mechanisms of action in combination against hepatitis B is theoretically an attractive approach for treatment. Although several studies have confirmed certain virological advantages of combination therapies, data supporting a long-term clinical benefit for patients are lacking and monotherapy with PegIFN or NAs remains the therapy of choice. Moreover, with the current treatment approaches, only a limited number of patients achieve hepatitis B surface antigen (HBsAg) loss. HBsAg loss is considered a "functional cure", but does not mean viral eradication. There is a need for novel therapeutic approaches that enable not only suppression of viral replication, but resolution of HBV infection. A key challenge is to target covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. The recent development and availability of innovative in vitro and in vivo systems and sensitive molecular techniques has opened new possibilities to study the complex network of interactions that HBV establishes with the host in the course of infection and to define new targets for antiviral strategies. Several new antiviral or immunomodulatory compounds have reached preclinical or clinical testing with the aim of silencing or eradicating cccDNA to achieve functional cure. Many of these strategies may also be effective for the treatment of HDV, which is dependent on HBsAg for its life cycle. This Clinical Trial Watch summarizes the most recent therapeutic strategies designed to directly target the viruses B and D or to improve immune responses during chronic HBV infection. PMID- 27270044 TI - Predicting Solvation Free Energies Using Parameter-Free Solvent Models. AB - We present a new approach for predicting solvation free energies in nonaqueous solvents. Utilizing the corresponding states principle, we estimate solvent Lennard-Jones parameters directly from their critical points. Combined with atomic solutes and the pressure corrected three-dimensional reference interaction site model (3D-RISM/PC+), the model gives accurate predictions for a wide range of nonpolar solvents, including olive oil. The results, obtained without electrostatic interactions and with a very coarse-grained solvent, provide an interesting alternative to widely used and heavily parametrized models. PMID- 27270045 TI - Modelling the Cost-Effectiveness of Delaying End-Stage Renal Disease. AB - BACKGROUND: As the incidence of end-stage renal disease (ESRD) is on the rise, new therapies are being developed for delaying ESRD. This study is aimed at constructing a generic model for estimating the cost-effectiveness of delaying ESRD in 7 European countries: the Netherlands, United Kingdom, Germany, Italy, Spain, Finland and Hungary. The use of this model is illustrated by assessing 2 fictitious, but realistic therapy options. METHODS: Quality-adjusted life years (QALYs) and societal costs were estimated using a state-transition model. Age dependent survival after renal replacement therapy was estimated using data from the Dutch Renal Registry. Healthcare costs and utilities were obtained from published reports. Country-specific differences regarding access to transplantation and value of productivity were factored. RESULTS: A 1-year delay of ESRD rendered an estimated gain of 0.6 QALYs and 0.3 years in productivity. Access to transplantation had a minimal impact, whereas savings on productivity had a significant impact. For a 1-year delay free of charge, societal savings would range from ?8,000 in the United Kingdom to ?17,000 in Germany. Applying thresholds of ?20,000-?40,000 per QALY gained, one-time cell-based therapy would be economically acceptable if it delayed ESRD by 0.2-0.5 years. It would be cost saving for a delay in excess of 0.5 years. Continuous use of medication is unlikely to be cost-effective for prices higher than ?30,000 per year. CONCLUSION: This study provides evidence for the economic potential of new therapies delaying ESRD. The constructed model provides users with information about the market success rates of treatment options at an early stage. PMID- 27270041 TI - Proliferation of Double-Strand Break-Resistant Polyploid Cells Requires Drosophila FANCD2. AB - Conserved DNA-damage responses (DDRs) sense genome damage and prevent mitosis of broken chromosomes. How cells lacking DDRs cope with broken chromosomes during mitosis is poorly understood. DDRs are frequently inactivated in cells with extra genomes (polyploidy), suggesting that study of polyploidy can reveal how cells with impaired DDRs/genome damage continue dividing. Here, we show that continued division and normal organ development occurs in polyploid, DDR-impaired Drosophila papillar cells. As papillar cells become polyploid, they naturally accumulate broken acentric chromosomes but do not apoptose/arrest the cell cycle. To survive mitosis with acentric chromosomes, papillar cells require Fanconi anemia proteins FANCD2 and FANCI, as well as Blm helicase, but not canonical DDR signaling. FANCD2 acts independently of previous S phases to promote alignment and segregation of acentric DNA produced by double-strand breaks, thus avoiding micronuclei and organ malformation. Because polyploidy and impaired DDRs can promote cancer, our findings provide insight into disease-relevant DNA-damage tolerance mechanisms. PMID- 27270046 TI - Cardamine hirsuta: a comparative view. AB - Current advances in developmental genetics are increasingly underpinned by comparative approaches as more powerful experimental tools become available in non-model organisms. Cardamine hirsuta is related to the model plant Arabidopsis thaliana and comparisons between these two experimentally tractable species have advanced our understanding of development and diversity. The power of forward genetics to uncover new biology was evident in the isolation of REDUCED COMPLEXITY, a gene which is present in C. hirsuta but lost in A. thaliana, and shapes crucifer leaf diversity. Transferring two Knotted1-like homeobox genes between C. hirsuta and A. thaliana revealed a constraint imposed by pleiotropy on the evolutionary potential of cis regulatory change to modify leaf shape. FLOWERING LOCUS C was identified as a heterochronic gene that underlies natural leaf shape variation in C. hirsuta. PMID- 27270048 TI - Ethical challenges in social media engagement and research: considerations for code of engagement practices. AB - Social media have great potential for effectively communicating about public health risks so people make healthier and safer choices. If used appropriately, social media can strengthen trust between the public and the institution. If used inappropriately, it may also create distrust. This note addresses some of the ethical challenges in using social media for communication and research. It reflects on opportunities in social media risk communication based on experience from the World Health Organization (WHO) and suggests a code of engagement be included in corporate social media policies that contain guidance as to what conduct is or is not appropriate with a view to maintaining public trust in the institution. The note concludes with considerations about the ethical use of social media in research, which is particularly relevant for entities communicating about ionizing radiation, including during emergency situations. PMID- 27270049 TI - Decarboxylative Cascade Reactions of Dihydroxyfumaric Acid: A Preparative Approach to the Glyoxylate Scenario. AB - An operationally simple protocol is reported to generate an alpha-hydroxyacyl anion by the decarboxylation of dihydroxyfumaric acid. To date, the "missing" utilization of the hydroxyacyl anion in highly chemo- and stereoselective cascade reactions enables short and direct construction of carbohydrates. PMID- 27270047 TI - Antioxidants as therapeutics in the intensive care unit: Have we ticked the redox boxes? AB - Critically ill patients are under oxidative stress and antioxidant administration reasonably emerged as a promising approach to combat the aberrant redox homeostasis in this patient cohort. However, the results of the antioxidant treatments in the intensive care unit are conflicting and inconclusive. The main objective of the present review is to highlight some inherent, yet widely overlooked redox-related issues about the equivocal effectiveness of antioxidants in the intensive care unit, beyond methodological considerations. In particular, the discrepancy in the literature partially stems from: (1) the largely unspecified role of reactive species in disease onset and progression, (2) our fragmentary understanding on the interplay between inflammation and oxidative stress, (3) the complex spatiotemporal specificity of in vivo redox biology, (4) the pleiotropic effects of antioxidants and (5) the divergent effects of antioxidants according to the temporal administration pattern. In addition, two novel and sophisticated practices with promising pre-clinical results are presented: (1) the selective neutralization of reactive species in key organelles after they are formed (i.e., in mitochondria) and (2) the targeted complete inhibition of dominant reactive species sources (i.e., NADPH oxidases). Finally, the reductive potential of NADPH as a key pharmacological target for redox therapies is rationalized. In light of the above, the recontextualization of knowledge from basic redox biology to translational medicine seems imperative to perform more realistic in vivo studies in the fast-growing field of critical care pharmacology. PMID- 27270051 TI - In This Issue * June 15, 2016. PMID- 27270050 TI - Unstable repeat expansion in major psychiatric disorders: two decades on, is dynamic DNA back on the menu? AB - For a period in the mid-1990s, soon after the discovery of the involvement of trinucleotide repeat expansions in fragile-X syndrome (both A and E), Huntington's disease, myotonic dystrophy, and a number of hereditary ataxias, there was a clear sense that this new disease mechanism might provide answers for psychiatric disorders. Given the then failures to replicate initial genetic linkage findings for schizophrenia (SCZ) and bipolar disorder (BD), a greater emphasis was placed on the role of complex and non-Mendelian mechanisms, and repeat instability appeared to have the potential to provide adequate explanations for numerous apparently non-Mendelian features such as anticipation, incomplete penetrance, sporadic occurrence, and nonconcordance of monozygotic twins. Initial molecular studies using a ligation-based amplification method (repeat expansion detection) appeared to support the involvement of CAG*CTG repeat expansion in SCZ and BD. However, subsequent studies that dissected the large repeats responsible for much of the positive signal showed that there were three main loci where CAG*CTG repeat expansion was occurring (on 13q21.33, 17q21.33-q22, and 18q21.2). None of the expansions at these loci appeared to segregate with SCZ or BD, and research into repeat expansions in psychiatric illness petered out in the early 2000s. The 13q expansion occurs within a noncoding RNA and appears to be associated with spinocerebellar ataxia 8 (SCA8), but with a still unexplained dichotomy in penetrance - either very high or very low. The 17q expansion occurs within an intron of the carbonic anhydrase-like gene, CA10. The 18q expansion is located within an intron of the TCF4 gene. Mutations in TCF4 are a known cause of Pitt-Hopkins syndrome. Also, pertinently, genome-wide association studies have shown a well-replicated association between TCF4 and SCZ. Two decades on, in 2016, it appears to be an appropriate juncture to reflect on what we have learned, and, with the arrival of newer technologies, whether there is any mileage to be made in revisiting the unstable DNA hypothesis for psychiatric illness. PMID- 27270053 TI - Letters to the Editor. PMID- 27270054 TI - What Is Your Diagnosis? PMID- 27270055 TI - Diagnostic Imaging in Veterinary Dental Practice. PMID- 27270056 TI - Pathology in Practice. PMID- 27270057 TI - Pathology in Practice. PMID- 27270059 TI - Comparison of tensile strength among simple interrupted, cruciate, intradermal, and subdermal suture patterns for incision closure in ex vivo canine skin specimens. AB - OBJECTIVE To compare suture placement time, tension at skin separation and suture line failure, and mode of failure among 4 suture patterns. DESIGN Randomized trial. SAMPLE 60 skin specimens from the pelvic limbs of 30 purpose-bred Beagles. PROCEDURES Skin specimens were harvested within 2 hours after euthanasia and tested within 6 hours after harvest. An 8-cm incision was made in each specimen and sutured with 1 of 4 randomly assigned suture patterns (simple interrupted, cruciate, intradermal, or subdermal). Suture placement time and percentage of skin apposition were evaluated. Specimens were mounted in a calibrated material testing machine and distracted until suture line failure. Tensile strength at skin-edge separation and suture-line failure and mode of failure were compared among the 4 patterns. RESULTS Mean suture placement time for the cruciate pattern was significantly less than that for other patterns. Percentage of skin apposition did not differ among the 4 patterns. Mean tensile strength at skin edge separation and suture-line failure for the simple interrupted and cruciate patterns were significantly higher than those for the intradermal and subdermal patterns. Mean tensile strength at skin-edge separation and suture-line failure did not differ significantly between the intradermal and subdermal patterns or the simple interrupted and cruciate patterns. The primary mode of failure for the simple interrupted pattern was suture breakage, whereas that for the cruciate, intradermal, and subdermal patterns was tissue failure. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested external skin sutures may be preferred for closure of incisions under tension to reduce risk of dehiscence. PMID- 27270060 TI - Risk factors for diskospondylitis in dogs after spinal decompression surgery for intervertebral disk herniation. AB - OBJECTIVE To determine the incidence of and risk factors for development of postoperative diskospondylitis (POD) in dogs that underwent spinal decompression surgery for intervertebral disk herniation (IVDH). DESIGN Retrospective single cohort study. ANIMALS 372 dogs that underwent spinal decompression surgery for IVDH between January 2007 and January 2011. PROCEDURES Medical records of dogs were retrospectively reviewed. Data regarding signalment, type and anatomic site of IVDH, severity of neurologic signs, type of surgery, duration of anesthesia, esophageal temperature during surgery, and use of corticosteroid drugs were analyzed for associations with POD. RESULTS POD developed in 8 of 372 (2.2%) dogs. Univariate analysis revealed that German Shepherd Dogs had 9.8 times the odds of POD, compared with the odds for other breeds. In addition, dogs > 8.8 years of age, weighing > 20 kg (44 lb), or having disk protrusions were at higher risk of developing POD than were other dogs. The only factor that retained a significant association with POD after controlling for other factors in multivariate analysis was body weight > 20 kg. CONCLUSIONS AND CLINICAL RELEVANCE Factors identified in this study may be useful for prediction of POD, an apparently uncommon outcome, in dogs undergoing spinal decompression surgery for IVDH. Dogs at higher risk than others, particularly those weighing > 20 kg, should be monitored carefully in the immediate postoperative period, and signs of worsening neurologic condition after initial improvement should be promptly investigated. PMID- 27270061 TI - New Veterinary Biologic Products. PMID- 27270062 TI - Sensitivity, specificity, and interobserver variability of survey thoracic radiography for the detection of heart base masses in dogs. AB - OBJECTIVE To determine the sensitivity, specificity, and interobserver variability of survey thoracic radiography (STR) for the detection of heart base masses (HBMs) in dogs. DESIGN Retrospective case-control study. ANIMALS 30 dogs with an HBM and 120 breed-matched control dogs (60 healthy dogs and 60 dogs with heart disease and no HBM). PROCEDURES In a blinded manner, 2 observers (designated as A and B) evaluated STR views from each dog for a mass-like opacity cranial to the heart, tracheal deviation, cardiomegaly, findings suggestive of pericardial effusion or right-sided congestive heart failure, and soft tissue opacities suggestive of pulmonary metastases. Investigators subsequently provided a final interpretation of each dog's HBM status (definitely affected, equivocal, or definitely not affected). RESULTS Considering equivocal interpretation as negative or positive for an HBM, the sensitivity of STR for diagnosis of an HBM was 40.0% (95% confidence interval [CI], 22.5% to 57.5%) and 56.7% (95% CI, 38.9% to 74.4%), respectively, for observer A and 63% (95% CI, 46.1% to 80.6%) and 80.0% (95% CI, 65.7% to 94.3%), respectively, for observer B. The corresponding specificity was 96.7% (95% CI, 93.5% to 99.9%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer A and 99.2% (95% CI, 97.5% to 100%) and 92.5% (95% CI, 87.8% to 97.2%), respectively, for observer B. The presence of a mass like opacity cranial to the heart or tracheal deviation, or both, was significantly associated with a true diagnosis of HBM. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that STR is a highly specific but not a highly sensitive predictor of HBM in dogs. PMID- 27270063 TI - Clinical diagnosis and surgical management of diaphragmatic retroperitoneal perirenal fat and kidney herniation in a pet rabbit. AB - CASE DESCRIPTION A 6-year-old 2.08-kg (4.58-lb) neutered male Lionhead-mix pet rabbit (Oryctolagus cuniculus) was examined because of sneezing and increased respiratory effort. CLINICAL FINDINGS On the basis of the rabbit's radiographic findings, a diagnosis of diaphragmatic retroperitoneal perirenal fat and kidney herniation was made. Nine months later, physical examination revealed increased respiratory rate and effort and slightly decreased body weight. Thoracic radiography revealed decreased lung aeration and further craniomedial displacement of the right kidney, compared with the initial evaluation findings, suggesting progressive herniation of the retroperitoneal perirenal fat. TREATMENT AND OUTCOME During exploratory celiotomy, a tear in the right dorsal tendinous portion of the diaphragm was noted. The right kidney and perirenal fat were found to be displaced into the thorax. Diaphragmatic herniorrhaphy was performed after replacement of the right kidney and the perirenal fat in the retroperitoneal space. The rabbit recovered uneventfully from anesthesia and surgery. Clinical signs did not recur during the following 16 months. CLINICAL RELEVANCE For rabbits with increased respiratory effort, diaphragmatic retroperitoneal perirenal fat and kidney herniation should be included as a differential diagnosis. As illustrated by the case described in this report, appropriate surgical management can provide a successful outcome for affected pet rabbits. PMID- 27270064 TI - Risk profiling of cattle farms as a potential tool in risk-based surveillance for Mycobacterium bovis infection among cattle in tuberculosis-free areas. AB - OBJECTIVE To develop a cattle herd risk-profiling system that could potentially inform risk-based surveillance strategies for Mycobacterium bovis infection in cattle and provide information that could be used to help direct resource allocation by a state agency for this purpose. DESIGN Cross-sectional study. SAMPLE Records for any size movement (importation) of cattle into Minnesota from other US states during 2009 (n = 7,185) and 2011 (8,107). PROCEDURES Data from certificates of veterinary inspection were entered into a spreadsheet. Movement data were summarized at premises and county levels, and for each level, the distribution of cattle moved and number of movements were evaluated. Risk profiling (assessment and categorization of risk for disease introduction) for each import movement was performed on the basis of known risk factors. Latent class analysis was used to assign movements to risk classifications with adjustment on the basis of expert opinions from personnel knowledgeable about bovine tuberculosis; these data were used to classify premises as very high, high, medium, or low risk for disease introduction. RESULTS In each year, approximately 1,500 premises imported cattle, typically beef and feeder types, with the peak of import movements during the fall season. The risk model identified 4 risk classes for cattle movements. Approximately 500 of the estimated 27,406 (2%) cattle premises in Minnesota were in the very high or high risk groups for either year; greatest density of these premises was in the southeast and southwest regions of the state. CONCLUSIONS AND CLINICAL RELEVANCE A risk-profiling approach was developed that can be applied in targeted surveillance efforts for bovine tuberculosis, particularly in disease-free areas. PMID- 27270065 TI - Association of gender and specialty interest with video-gaming, three-dimensional spatial analysis, and entry-level laparoscopic skills in third-year veterinary students. AB - OBJECTIVE To determine whether gender or interest in pursuing specialty certification in internal medicine or surgery was associated with video-gaming, 3 D spatial analysis, or entry-level laparoscopic skills in third-year veterinary students. DESIGN Cross-sectional study. SAMPLE A convenience sample of 68 (42 female and 26 male) third-year veterinary students. PROCEDURES Participants completed a survey asking about their interest in pursuing specialty certification in internal medicine or surgery. Subsequently, participants' entry level laparoscopic skills were assessed with 3 procedures performed in box trainers, their video-gaming skills were tested with 3 video games, and their 3-D spatial analysis skills were evaluated with the Purdue University Visualization of Rotations Spatial Test. Scores were assigned for laparoscopic, video-gaming, and 3-D spatial analysis skills. RESULTS Significantly more female than male students were interested in pursuing specialty certification in internal medicine (23/42 vs 7/26), and significantly more male than female students were interested in pursuing specialty certification in surgery (19/26 vs 19/42). Males had significantly higher video-gaming skills scores than did females, but spatial analysis and laparoscopic skills scores did not differ between males and females. Students interested in pursuing specialty certification in surgery had higher video-gaming and spatial analysis skills scores than did students interested in pursuing specialty certification in internal medicine, but laparoscopic skills scores did not differ between these 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE For this group of students, neither gender nor interest in specialty certification in internal medicine versus surgery was associated with entry-level laparoscopy skills. PMID- 27270066 TI - Assessment of pediatric Malone antegrade continence enema (MACE) complications: Effects of variations in technique. AB - OBJECTIVE: The Malone antegrade continence enema (MACE) procedure is performed for patients with fecal incontinence and constipation who do not respond to medical therapy. The MACE procedure provides antegrade catheter access to the right colon and allows administration of enemas to help evacuate the bowel regularly. The objective of this study was to identify risk factors for surgical complications in children who undergo the MACE procedure. METHOD: Records from 97 pediatric patients who underwent MACE procedure were reviewed retrospectively. Data collected included age, sex, weight (obese/not obese), stomal location, presence of a permanent button/catheter in the stoma, open vs. laparoscopic surgery, and etiology of fecal incontinence/constipation. The complications reviewed included stomal stenosis, leakage, and stomal site infection. The relationships between the independent variables and complications were assessed using chi-square tests and Fisher's exact test. Statistical significance was set at p < 0.05. RESULTS: Overall, 66 (68%) patients had at least one complication. Twenty-three (23.7%) patients developed stomal stenosis, and 27 (27.8%) patients had significant stomal leakage. Insertion of a stomal button/catheter device was associated with an increased risk of developing stomal leakage and stomal infection. The presence of a stomal button/catheter was also associated with a decreased risk of stomal stenosis (Figure). The non-intubated, imbricated sub population, preteen patients (<12 years old) experienced more stomal leakage than teenage patients. In this subgroup, patients with umbilical stomas also experienced more leakage than patients with right lower quadrant (RLQ) stomas. CONCLUSION: The prevalence rates of stomal complications in our study were consistent with previously reported series. In our study, however, stomal leakage had a higher prevalence in comparison with stomal stenosis. This seems to be related to the heterogeneity of the study group, which contained two variants of the MACE procedure; non-imbricated, intubated MACE and imbricated, non-intubated MACE. The use of stomal buttons in conjunction with MACE has previously been reported without changes in complication rates. We found the use of stomal buttons/catheters to be associated with changes in the prevalence of stomal complications. Stomal complications are common in the MACE procedure. The use of a permanent stomal button/catheter is associated with changes in the rates of stomal complications. While many find an umbilical stomal site is more cosmetically appealing, there is an increased risk of leakage with imbricated, non-intubated stomas. In the non-intubated, imbricated sub-population, the MACE procedure results in a higher risk of stomal leakage in preteen patients in comparison with teenage patients. PMID- 27270067 TI - What is the impact of simple ligation on patent processus vaginalis? PMID- 27270068 TI - Does endoscopy of difficult to catheterize channels spare some patients from formal open revision? AB - INTRODUCTION: Patients with continent catheterizable channels (CCC) may develop difficulty catheterizing postoperatively. In complex cases, endoscopic evaluation with indwelling catheter placement may be indicated, but the risk factors for subsequent formal channel revision are not well defined. The purpose of this study was to determine the risk factors for formal channel revision after attempted endoscopic management of difficulty catheterizing. MATERIALS AND METHODS: We performed an IRB-approved retrospective review of pediatric (<21 years old) patients undergoing CCC construction at our institution from 1999 to 2014 to identify patients who underwent endoscopy for difficulty catheterizing. Fisher's Exact test was used for categorical data and Mann-Whitney U test for continuous variables to examine the association between endoscopic intervention and subsequent formal revision. RESULTS: Sixty-three of 434 patients (14.5%) underwent at least one endoscopy for reported difficulty catheterizing their CCC, with 77.8% of these requiring additional intervention during endoscopy (catheter placement, dilation, etc.). Of these, almost half with functioning channels (43.5%, 27/62) were managed successfully with endoscopy without formal revision; six (22.2%) of whom underwent more than one endoscopy. These 27 patients continued to catheterize well at a median follow-up of 3.2 years (interquartile range 2.0-6.0). Patients requiring revision had a median of 1.7 years between CCC creation and first endoscopy, versus 1.6 years in those who were not revised (p = 0.60). There was no statistically significant difference between revised and non revised channels in terms of patient age at CCC creation, underlying patient diagnosis, status of bladder neck, stomal location, or channel type (p >= 0.05) (see Table). CONCLUSION: Approximately half of our patients did not require a formal channel revision after endoscopic management. We did not identify any specific risk factors for subsequent formal revision of a CCC. We recommend performing at least one endoscopic evaluation for those with difficulty catheterizing prior to proceeding with formal open revision. PMID- 27270069 TI - Standardized process to improve patient flow from the Emergency Room to the Operating Room for pediatric patients with testicular torsion. AB - BACKGROUND: Testicular torsion (TT) remains one of the most common urological emergencies. The length of time from onset of symptoms to detorsion and degree of spermatic cord twisting are usually the most important factors for testicular damage. Therefore early presentation, accurate diagnosis, and prompt treatment are important factors for optimizing the testicular salvage rate. While delay in seeking medical attention is a common cause of testicular loss in pediatric patients with testicular torsion, delays in diagnosis and treatment can be preventable causes of testicular loss. OBJECTIVE: In this study, we aimed to develop a standardized process to improve the patient flow from the Emergency Room (ER) to Operating Room (OR) for TT patients in an academic children's hospital. STUDY DESIGN: Thirty consecutive pediatric patients with acute testicular torsion between November 2013 and July 2014 served as the control group. A scrotal pain checklist was implemented in July 2014, and 30 consecutive patients from July 2014 until April 2015 served as the study group. Perioperative parameters including times, ultrasound (US) findings, and surgical results were reviewed. RESULTS: The mean ages of the control group and the study group were similar (12.3 +/- 4.9 years and 11.5 +/- 5 years, respectively) (p = 0.575). ER arrival to OR time, triage completion to OR time, and scrotal US to OR time were significantly decreased in the study group (p < 0.001) (Table). Although triage time and ER arrival to scrotal US times were decreased in the study group, the differences were not significant (p = 0.071, p = 0.112, respectively). DISCUSSION: Utilizing scoring tools during the triage of patients with scrotal pain can help identify high-risk patients earlier and prevent unnecessary use of resources in an ER serving a large pediatric population. Limitations of this pilot study include the limited number of patients and the potential for the Hawthorne effect (staff awareness of the study). Additionally, we did not examine scrotal pain checklist scores for other acute scrotal diseases. This study focused on a quality improvement process for TT patients, in order to reduce ER to OR times. CONCLUSION: A standardized process with use of a scrotal pain checklist and prompt communication between the ER, Urology, and Radiology teams led to significantly reduced times from the ER to the OR. Standardized processes for pediatric patients with testicular torsion may help to improve testicular survival rates. PMID- 27270070 TI - Barriers to transition in young adults with neurogenic bladder. AB - INTRODUCTION: 'Transition' not only involves finding an adult healthcare provider, but also includes the process of developing the patient's ability to care for him/herself. Recent literature states that 40% of young adults with special healthcare needs are receiving the tools needed for transition. Pediatric urologists treating patients with complex anomalies, such as spina bifida, often anticipate poor outcomes for patients who are ill equipped for transition to adult care. The goal of this study was to identify potential barriers for young adults with neurogenic bladder when transitioning to independent care. STUDY DESIGN: A prospective IRB-approved study was performed on all patients with neurogenic bladder referred to the transitional urology clinic. Reasons for missed appointments were tracked, and all patients were asked to complete the Transition Readiness Assessment Questionnaire (TRAQ) in private prior to an appointment. The TRAQ responses are scaled 1-5, with higher numbers corresponding to higher transition readiness of each individual skill. The mean score for each question was calculated across all patients, and the mean TRAQ score was calculated across all questions for each patient. To assess if certain subgroups were more prepared for transition, mean scores were compared between sexes, patients aged <19 and >=19 years old, and between ambulatory and full-time wheelchair users with unpaired t-tests. RESULTS: A total of 73% (58/79) of patients referred to the transitional clinic came to their appointment. The most common reason for missed clinic appointments was related to health insurance coverage (47%). A total of 42 patients completed the TRAQ at a mean age of 19.5 years old; 90% (38/42) had spina bifida. Females, ambulatory patients, and those >=19 years old had higher overall mean TRAQ scores, but these differences were not statistically significant. The highest TRAQ scores were related to taking and ordering medications, utilization of medical supplies, communication with healthcare providers, and assisting with household duties. The majority of the patients indicated 'I am learning to do this'. The lowest scores were in response to questions about health insurance coverage, payments for medications or medical equipment, financial help, and utilization of community services. Most patients responded 'I do not know how but I want to learn'. CONCLUSIONS: Young adults with neurogenic bladder needed the most guidance during transition to independent care, with management of health insurance and finances. Based on these findings, dedicated social work and nurse visits have been included into the transition process. PMID- 27270071 TI - The effect of gender equality on happiness: Statistical modeling and analysis. AB - In this article, the researcher presents linear regression models that describe how five gender-equality indexes affect individuals' perceptions of well-being and happiness, controlling for their economic income and weighed by the population of the countries that contribute to the models. The logical premise of this study is that gender equality is not only favorable for women, but it is also conducive to fostering the greatest level of happiness for all people. The researcher believes that most findings confirmed this assumption and the opinion of John Stuart Mill regarding gender equality, while two exceptions are explained by social quality theory and the male breadwinner model. PMID- 27270072 TI - Hospital Disaster Preparedness in Italy: a preliminary study utilizing the World Health Organization Hospital Emergency Response Evaluation Toolkit. AB - BACKGROUND: Natural and human-initiated disasters are occurring with greater devastating consequences and increased frequency. During these events, hospitals have the burden to care for acutely ill and injured patients. The aim of this study was to evaluate the level of disaster preparedness of Italian hospitals. METHODS: Site visits were conducted from January, 2014 to December, 2014. The hospital emergency response checklist, developed by the WHO, was used as an evaluation toolkit. It consists of 92 items classified as 9 key components, such as command and control, triage, and critical services. The status of each component was determined by consensus of 3 independent evaluators. RESULTS: The study selected 15 hospitals from different areas in Italy. Out of the 15 hospitals, 12 were considered to be at insufficients level of preparedness, only 3 were considered to have an effective level of preparedness. The average preparedness of all components were lower than the optimal level suggested by the WHO checklist. CONCLUSIONS: The study revealed that a large majority of Italian hospitals evaluated are not well prepared to manage potential disasters. Also, all important elements of hospital preparedness, such as the command system, surge capacity, and safety, were insufficiently implemented. Nationwide standards, guidelines and procedures are required to improve hospital disaster preparedness in Italy. PMID- 27270073 TI - Transesophageal echocardiography: what the anesthesiologist has to know. AB - Transesophageal echocardiography (TEE) is a very powerful intraoperative monitoring tool. It allows precise assessment of cardiac anatomy together with dynamic quantification of myocardial performance and flows through the heart chambers. With a high safety profile TEE counts few absolute contraindications. Performance of TEE requires dedicated training. Certification pathways are offered in Europe and North America. Focused, basic and advanced scanning protocols have been lately described for intraoperative and emergent use. Many specific TEE applications have been described in non-cardiac surgery most of which only supported by a limited number of studies. Advanced TEE allows quantitative assessment of left and right ventricular function but its application has not become standard of care outside the cardiac operative room partially due to lack of scientific evidence. TEE can provide quantification of left ad right ventricular cardiac output and diastolic function. It may also identify fluid responsiveness. TEE is more sensitive than ECG in identifying myocardial ischemia but it requires advanced training. Basic TEE can identify common causes of hemodynamic instability such as hypovolemia, pulmonary embolism and tamponade. Unexplained hemodynamic instability is the only strong indication in non-cardiac surgery. Qualitative assessment based on a simplified protocol seams to adequately address the clinical needs in this specific scenario. More studies are required to support the use of TEE outside of cardiac surgery at its full potential. PMID- 27270074 TI - Posterior reversible encephalopathy syndrome in acute pancreatitis. PMID- 27270075 TI - The Incidence of and Factors Associated with Vitamin D Deficiency in Newly Diagnosed Children with Cancer. AB - This retrospective chart review study aimed to assess vitamin D status and identify risk factors associated with vitamin D deficiency and bone parameters in children with cancer at admission. The data of 86 (50 males and 36 females) patients between April 2013 and June 2015 were analyzed. Calcium, phosphorus, alkaline phosphatase (ALP), 25(OH)D, age, gender, diagnostic category, body mass index, duration of complaints, and season of blood sampling were recorded. Median age was 7.17 years (range 0.31-17.40) in 29 hematological malignancy and 57 solid tumor patients. According to cut-off level of 20 ng/ml, 63% of children with cancer had vitamin D deficiency at diagnosis with a median 25(OH)D of 16.75 ng/ml. The mean vitamin D value of children >10 years was significantly low in comparison to that observed in younger children [11.83, 95% confidence interval (CI) = = 8.85-14.81 ng/ml vs. 19.81, 95% CI = = 17.02-22.60 ng/ml]. Vitamin D measurement between November and May was a risk factor for vitamin D deficiency (P < 0.05). The frequency of hypocalcemia and hypophosphatemia was not different between two groups of vitamin D. Further longitudinal studies are needed to investigate whether monitoring vitamin D status and supplementation in children with cancer might prevent future complications related to vitamin D deficiency. PMID- 27270076 TI - Multi-informant perspective on psychological distress among Ghanaian orphans and vulnerable children within the context of HIV/AIDS. AB - BACKGROUND: There is little knowledge about the psychosocial distress of children affected by human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) in Ghana, to aid the planning of services. This study investigated mental health problems among children affected by HIV/AIDS, compared with control groups of children orphaned by other causes, and non-orphans. METHOD: The study employed a cross-sectional survey that interviewed 291 children and their caregivers. Both children and caregivers completed the Strengths and Difficulties Questionnaire that measured children's psychosocial wellbeing. Verbal autopsy was used to identify whether children lost one or both parents from AIDS. RESULTS: The results indicated that controlling for relevant sociodemographic factors, both children's self-reports and caregivers' reports indicate that both children living with HIV/AIDS-infected caregivers and children orphaned by AIDS were at heightened risk for mental health problems than both children orphaned by other causes and non-orphans. The findings further indicated that a significant proportion of orphaned and vulnerable children exhibited symptoms for depression and other psychiatric disorders (approximately 63%) compared with 7% among the non-orphaned group. Caregivers gave higher ratings for children on externalizing problems and lower on internalizing problems, and vice versa when the children's self-reports were analysed. CONCLUSIONS: The findings suggest that both children and their informants have diverse yet complementary perspectives on psychological outcomes. The study discusses the theoretical and practical implications of these findings and urgently calls for necessary intervention programmes that target all children affected by HIV/AIDS to effectively alleviate psychological distress and enhance the mental health of these children. PMID- 27270077 TI - Cultural modes of expressing emotions influence how emotions are experienced. AB - The brain's mapping of bodily responses during emotion contributes to emotional experiences, or feelings. Culture influences emotional expressiveness, that is, the magnitude of individuals' bodily responses during emotion. So, are cultural influences on behavioral expressiveness associated with differences in how individuals experience emotion? Chinese and American young adults reported how strongly admiration- and compassion-inducing stories made them feel, first in a private interview and then during functional magnetic resonance imaging (fMRI). As expected, Americans were more expressive in the interview. Although expressiveness did not predict stronger reported feelings or neural responses during fMRI, in both cultural groups more-expressive people showed tighter trial by-trial correlations between their experienced strength of emotion and activations in visceral-somatosensory cortex, even after controlling for individuals' overall strength of reactions (neural and felt). Moreover, expressiveness mediated a previously described cultural effect in which activations in visceral-somatosensory cortex correlated with feeling strength among Americans but not among Chinese. Post hoc supplementary analyses revealed that more-expressive individuals reached peak activation of visceral somatosensory cortex later in the emotion process and took longer to decide how strongly they felt. The results together suggest that differences in expressiveness correspond to differences in how somatosensory mechanisms contribute to constructing conscious feelings. By influencing expressiveness, culture may therefore influence how individuals know how strongly they feel, what conscious feelings are based on, or possibly what strong versus weak emotions "feel like." (PsycINFO Database Record PMID- 27270078 TI - Parthenolide ameliorates Concanavalin A-induced acute hepatitis in mice and modulates the macrophages to an anti-inflammatory state. AB - Parthenolide, the principal sesquiterpene lactone present in medicinal plants such as feverfew, has anti-microbial, anti-inflammatory and anticancer activities. In the present study, we investigated the protective role of parthenolide against acute hepatitis in mice. Mice acute hepatitis were induced by Concanavalin A and treated by parthenolide in vivo. Results shown that parthenolide remarkably reduced the congestion and necroinflammation of the mice livers with Concanavalin A-induced acute hepatitis. Meanwhile, parthenolide treatment recover the liver function which indicated by decreased the serum alanine transaminase and alkaline phosphatase activities and promoted the expression of Ki67 in the livers of these mice. In addition, parthenolide administration suppressed the Concanavalin A-induced immune reaction, as indicated by the number of F4/80, CD49b and CD4 cells present in the liver. Furthermore, parthenolide also significantly reduced the expression of pro inflammatory cytokines such as IFN-gamma, TNF-alpha, IL-17A, IL-1beta and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in vitro. Moreover, parthenolide exposure decreased the phosphorylation of STAT3 and p38, and promoted the phosphorylation of p53 in RAW264.7 cells in vitro. In conclusion, parthenolide represents a drug candidate to protect the liver against Concanavalin A-induced acute hepatitis. The possible molecular mechanism involves the anti-inflammatory effects of parthenolide may by suppressing the STAT3/p38 signals and enhanced the p53 signals. PMID- 27270079 TI - FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing. AB - Allele-specific copy number analysis (ASCN) from next generation sequencing (NGS) data can greatly extend the utility of NGS beyond the identification of mutations to precisely annotate the genome for the detection of homozygous/heterozygous deletions, copy-neutral loss-of-heterozygosity (LOH), allele-specific gains/amplifications. In addition, as targeted gene panels are increasingly used in clinical sequencing studies for the detection of 'actionable' mutations and copy number alterations to guide treatment decisions, accurate, tumor purity-, ploidy- and clonal heterogeneity-adjusted integer copy number calls are greatly needed to more reliably interpret NGS-based cancer gene copy number data in the context of clinical sequencing. We developed FACETS, an ASCN tool and open-source software with a broad application to whole genome, whole-exome, as well as targeted panel sequencing platforms. It is a fully integrated stand-alone pipeline that includes sequencing BAM file post-processing, joint segmentation of total- and allele-specific read counts, and integer copy number calls corrected for tumor purity, ploidy and clonal heterogeneity, with comprehensive output and integrated visualization. We demonstrate the application of FACETS using The Cancer Genome Atlas (TCGA) whole-exome sequencing of lung adenocarcinoma samples. We also demonstrate its application to a clinical sequencing platform based on a targeted gene panel. PMID- 27270080 TI - Differential sensitivity to methylated DNA by ETS-family transcription factors is intrinsically encoded in their DNA-binding domains. AB - Transactivation by the ETS family of transcription factors, whose members share structurally conserved DNA-binding domains, is variably sensitive to methylation of their target genes. The mechanism by which DNA methylation controls ETS proteins remains poorly understood. Uncertainly also pervades the effects of hemi methylated DNA, which occurs following DNA replication and in response to hypomethylating agents, on site recognition by ETS proteins. To address these questions, we measured the affinities of two sequence-divergent ETS homologs, PU.1 and Ets-1, to DNA sites harboring a hemi- and fully methylated CpG dinucleotide. While the two proteins bound unmethylated DNA with indistinguishable affinity, their affinities to methylated DNA are markedly heterogeneous and exhibit major energetic coupling between the two CpG methylcytosines. Analysis of simulated DNA and existing co-crystal structures revealed that hemi-methylation induced non-local backbone and groove geometries that were not conserved in the fully methylated state. Indirect readout of these perturbations was differentially achieved by the two ETS homologs, with the distinctive interfacial hydration in PU.1/DNA binding moderating the inhibitory effects of DNA methylation on binding. This data established a biophysical basis for the pioneering properties associated with PU.1, which robustly bound fully methylated DNA, but not Ets-1, which was substantially inhibited. PMID- 27270082 TI - Type II restriction endonucleases - a historical perspective and more. PMID- 27270081 TI - Conformational selection and dynamic adaptation upon linker histone binding to the nucleosome. AB - Linker histones are essential for DNA compaction in chromatin. They bind to nucleosomes in a 1:1 ratio forming chromatosomes. Alternative configurations have been proposed in which the globular domain of the linker histone H5 (gH5) is positioned either on- or off-dyad between the nucleosomal and linker DNAs. However, the dynamic pathways of chromatosome assembly remain elusive. Here, we studied the conformational plasticity of gH5 in unbound and off-dyad nucleosome bound forms with classical and accelerated molecular dynamics simulations. We find that the unbound gH5 converts between open and closed conformations, preferring the closed form. However, the open gH5 contributes to a more rigid chromatosome and restricts the motion of the nearby linker DNA through hydrophobic interactions with thymidines. Moreover, the closed gH5 opens and reorients in accelerated simulations of the chromatosome. Brownian dynamics simulations of chromatosome assembly, accounting for a range of amplitudes of nucleosome opening and different nucleosome DNA sequences, support the existence of both on- and off-dyad binding modes of gH5 and reveal alternative, sequence and conformation-dependent chromatosome configurations. Taken together, these findings suggest that the conformational dynamics of linker histones and nucleosomes facilitate alternative chromatosome configurations through an interplay between induced fit and conformational selection. PMID- 27270084 TI - Finite-size scaling in a 2D disordered electron gas with spectral nodes. AB - We study the DC conductivity of a weakly disordered 2D electron gas with two bands and spectral nodes, employing the field theoretical version of the Kubo Greenwood conductivity formula. Disorder scattering is treated within the standard perturbation theory by summing up ladder and maximally crossed diagrams. The emergent gapless (diffusion) modes determine the behavior of the conductivity on large scales. We find a finite conductivity with an intermediate logarithmic finite-size scaling towards smaller conductivities but do not obtain the logarithmic divergence of the weak-localization approach. Our results agree with the experimentally observed logarithmic scaling of the conductivity in graphene with the formation of a plateau near [Formula: see text]. PMID- 27270083 TI - Multiplexed miRNA northern blots via hybridization chain reaction. AB - Northern blots enable detection of a target RNA of interest in a biological sample using standard benchtop equipment. miRNAs are the most challenging targets as they must be detected with a single short nucleic acid probe. With existing approaches, it is cumbersome to perform multiplexed blots in which several RNAs are detected simultaneously, impeding the study of interacting regulatory elements. Here, we address this shortcoming by demonstrating multiplexed northern blotting based on the mechanism of hybridization chain reaction (HCR). With this approach, nucleic acid probes complementary to RNA targets trigger chain reactions in which fluorophore-labeled DNA hairpins self-assemble into tethered fluorescent amplification polymers. The programmability of HCR allows multiple amplifiers to operate simultaneously and independently within a blot, enabling straightforward multiplexing. We demonstrate simultaneous detection of three endogenous miRNAs in total RNA extracted from 293T and HeLa cells. For a given target, HCR signal scales linearly with target abundance, enabling relative and absolute quantitation. Using non-radioactive HCR, sensitive and selective miRNA detection is achieved using 2'OMe-RNA probes. The HCR northern blot protocol takes ~1.5 days independent of the number of target RNAs. PMID- 27270085 TI - Simultaneous optical and electrical in vivo analysis of the enteric nervous system. AB - The enteric nervous system (ENS) is a major division of the nervous system and vital to the gastrointestinal (GI) tract and its communication with the rest of the body. Unlike the brain and spinal cord, relatively little is known about the ENS in part because of the inability to directly monitor its activity in live animals. Here, we integrate a transparent graphene sensor with a customized abdominal window for simultaneous optical and electrical recording of the ENS in vivo. The implanted device captures ENS responses to neurotransmitters, drugs and optogenetic manipulation in real time. PMID- 27270086 TI - Jejunal diverticulosis: A rare cause of intestinal obstruction. PMID- 27270097 TI - [(18)F]Fluoroethyl Triazole Substituted PSMA Inhibitor Exhibiting Rapid Normal Organ Clearance. AB - Prostate-specific membrane antigen (PSMA) is overexpressed in the epithelium of prostate cancer and nonprostate solid tumor neovasculature. PSMA is increasingly utilized as a target for cancer imaging and therapy. Here, we report the synthesis and in vivo biodistribution of a low-molecular-weight PSMA-based imaging agent, 2-[3-(1-carboxy-5-{3-[1-(2-[(18)F]fluoroethyl)-1H-1,2,3-triazol yl]propanamido}pentyl)ureido]pentanedioic acid ([(18)F]YC-88), containing an [(18)F]fluoroethyl triazole moiety. [(18)F]YC-88 was synthesized from 2 [(18)F]fluoroethyl azide and the corresponding alkyne precursor in two steps using either a one- or two-pot procedure. Biodistribution and positron emission tomography (PET) imaging were performed in immunocompromised mice using isogenic PSMA(+) PC3 PIP and PSMA(-) PC3 flu xenografts. YC-88 exhibited high affinity for PSMA as evidenced by a Ki value of 12.9 nM. The non-decay corrected radiochemical yields of [(18)F]YC-88 averaged 14 +/- 1% (n = 5). Specific radioactivities ranged from 320 to 2,460 Ci/mmol (12-91 GBq/MUmol) with an average of 940 Ci/mmol (35 GBq/MUmol, n = 5). In an immunocompromised mouse model, [(18)F]YC-88 clearly delineated PSMA(+) PC3 PIP prostate tumor xenografts on imaging with PET. At 1 h postinjection, 47.58 +/- 5.19% injected dose per gram of tissue (% ID/g) was evident within the PSMA(+) PC3 PIP tumor, with a ratio of 170:1 of uptake within PSMA(+) PC3 PIP to PSMA(-) PC3 flu tumor placed in the opposite flank. The tumor to-kidney ratio at 2 h postinjection was 4:1. At or after 30 min postinjection, minimal nontarget tissue uptake of [(18)F]YC-88 was observed. Compared to [(18)F]DCFPyL, which is currently in clinical trials, the uptake of [(18)F]YC-88 within the kidney, liver, and spleen was significantly lower at all time-points studied. At 30 min and 1 h postinjection, salivary gland uptake of [(18)F]YC-88 was significantly less than that of [(18)F]DCFPyL. [(18)F]YC-88 is a new PSMA targeted PET agent synthesized utilizing click chemistry that demonstrates high PSMA(+) tumor uptake in a xenograft model. Because of its low uptake in the kidney, rapid clearance from nontarget organs, and relatively simple one-pot, two step radiosynthesis, [(18)F]YC-88 is a viable new PET radiotracer for imaging PSMA-expressing lesions. PMID- 27270098 TI - Digital Dermoscopy Photographs Outperform Handheld Dermoscopy in Melanoma Diagnosis. AB - BACKGROUND: Pigmented lesion clinics (PLCs) that use technology such as digital dermoscopy and total-body photography are thought to confer a clinical advantage for patients at high risk of developing melanoma over general dermatology clinics (GDCs) with regular dermoscopy. OBJECTIVE: To examine the difference between depths of melanomas diagnosed in a PLC and a GDC. METHODS: Medical records from 257 patients at the PLC at The Ottawa Hospital and 441 patients from a GDC were reviewed. RESULTS: Invasive melanoma was less frequent than in situ melanoma at the PLC (7.14% vs 38.27%; P = .02). The average Breslow depth for melanomas at the PLC was also smaller compared with the GDC (0.0371 vs 0.3450 mm; P = .02). CONCLUSIONS: The use of digital dermoscopy and total-body photography together in a PLC appears to be an effective way to monitor patients at high risk of melanoma. PMID- 27270099 TI - Characterization of Kinetic Binding Properties of Unlabeled Ligands via a Preincubation Endpoint Binding Approach. AB - The dissociation rates of unlabeled drugs have been well studied by kinetic binding analyses. Since kinetic assays are laborious, we developed a simple method to determine the kinetic binding parameters of unlabeled competitors by a preincubation endpoint assay. The probe binding after preincubation of a competitor can be described by a single equation as a function of time. Simulations using the equation revealed the degree of IC50 change induced by preincubation of a competitor depended on the dissociation rate koff of the competitor but not on the association rate kon To validate the model, an in vitro binding assay was performed using a smoothened receptor (SMO) and [(3)H]TAK-441, a SMO antagonist. The equilibrium dissociation constants (KI) and koff of SMO antagonists determined by globally fitting the model to the concentration response curves obtained with and without 24 h preincubation correlated well with those determined by other methods. This approach could be useful for early-stage optimization of drug candidates by enabling determination of binding kinetics in a high-throughput manner because it does not require kinetic measurements, an intermediate washout step during the reaction, or prior determination of competitors' KI values. PMID- 27270100 TI - Analysis of beta2-agonists in cattle hair samples using a rapid UHPLC-ESI-MS/MS method. AB - A simple and efficient method was developed for simultaneous analysis of five illegal residual beta2-agonists in cattle hair. beta2-Agonists were quantified by ultra high performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry operating in positive multiple-reaction monitoring mode. The method was validated as quantitative confirmatory method according to the EU Decision 2002/657/EC: instrumental linearity, specificity, precision, recovery, decision limit (CCalpha) and detection capability (CCbeta) were evaluated. The recovery were greater than 90% and the method appeared suitable for the control of these beta2-agonists in cattle hair samples with LOQ values between 4.9 and 5.5 MUg/kg. This method could represent a simple and cheap approach to confirm beta2-agonists contamination of cattle for feeding in a not invasive way and before slaughter operations. PMID- 27270101 TI - Electrocautery effect on intestinal vascularisation in a murine model. AB - BACKGROUND: The use of electrocautery devices is associated with complications such as perforation or fistulisation when used near intestinal structures. This is likely due to its effect on vascularisation of the bowel wall. To test this hypothesis we established a murine model to quantify the effect of electrocautery injury on the intestinal microvascularisation. METHODS: Sprague-Dawley rats were subjected to five electrocautery injuries on the small bowel in coagulation mode (30 W intensity) and in cut mode (40 W, 80 W and 200 W intensities) for durations of 1, 2 and 5 s. 5 mg/kg of fluorescein was injected intravenously, the injured bowel segments harvested and the rat sacrificed. The segments were analysed to measure the fluorescence of injured bowel compared to adjacent unharmed tissue. RESULTS: A significant decrease in bowel wall microvascularisation occurred with increasing intensity (coag 30 W/cut 40 W versus cut 200 W 1 s: p < 0.05) and duration of electrocautery injury (cut 40 W 1/2 s versus 5 s: p < 0.05). There was a 40% perforation rate when decreased bowel wall microvascularisation was 25% or more. Despite similar electrocautery injury, a significantly greater microvascularisation decrease was observed in jejunum compared to ileum (p < 0.05). CONCLUSION: We successfully established a murine model to quantify the decrease of bowel wall microvascularisation associated with electrocautery use. Unsurprisingly, the decrease in microvascularisation is greater with higher intensity and duration of electrocautery and is associated with more perforations in the experimental model. The jejunum seems more vulnerable to electrocautery injury than the ileum. These observations support caution when using electrocautery devices near intestinal structures. PMID- 27270102 TI - Rate of skill acquisition in the use of a robotic laparoscope holder (FreeHand((r))). AB - BACKGROUND: Robotic equipment can greatly add to the ergonomics of a surgical procedure and pre-operative simulation can provide risk-free training of the surgeon leading to precision surgery and less trauma to the patient. Freehand((r)) is a second-generation robotic camera-holding device, which has recently become available to laparoscopic surgeons. It is controlled by the operator selecting a direction using head movement followed by activation with a foot pedal. The purpose of this study was to assess the rate of skill acquisition in the use of the FreeHand((r)) robotic laparoscope holder by a group of laparoscopic surgeons by enrolling them into a programme of training modules at The ICENI Centre, Colchester Hospital University, UK. MATERIAL AND METHODS: Twenty surgical registrars performed a series of exercises, escalating in difficulty, to test their skill in controlling the FreeHand((r)) robot. Subjective and objective assessments were evaluated by an observer and by tracking analysis software created for this trial. RESULTS: The observed number of head movements showed a Percentage Performance Score (PPS) of 98% by the end of the third repetition of all exercises, the mean Total Head Movements Score (HMS) reached a plateau of performance at 72%. Fifty per cent of the participants selected 'Effective control of movements without difficulty' in the subjective evaluation by the end of the third repetition of exercises, while 35% selected 'competent intuitive movements'. CONCLUSION: The FreeHand((r)) robotic laparoscope holder is a useful device, which is easy to operate and requires a very short course of training to achieve competence in its use. PMID- 27270103 TI - Two-stage screening for early dementia in primary care. AB - OBJECTIVE: The objective was to compare two screening strategies for dementia in an urban primary care clinic, serving a low-education, minority community composed largely of Latino and African American patients. METHOD: Two hundred and fifty-seven patients underwent two-stage patient-based screening (PBS) and informant-based screening (IBS) followed by a diagnostic evaluation. In the first stage, PBS included brief tests of episodic memory (Memory Impairment Screen), semantic memory (Animal Fluency), and executive function (Reciting Months Backwards). For IBS, the first stage consisted of the short Informant Questionnaire on Cognitive Decline in the Elderly, administered to a family member or friend. Patients who screened positive in the first stage of either strategy underwent testing with the picture version of the Free and Cued Selective Reminding Test with Immediate Recall to identify memory impairment. Sensitivity, specificity, and positive and negative predictive values were computed for various cutoffs of each test and combination of tests. Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria without access to the screening test results. RESULTS: We identified 66 patients (25.7%) with previously undiagnosed dementia. Sensitivity was the same (77%) for both strategies but specificity was higher for IBS than for PBS (92% versus 83%). IBS's higher specificity makes it the preferred strategy if a knowledgeable informant is available. CONCLUSION: Unrecognized dementia is common in primary care. Case-finding can be improved using either PBS or IBS two-stage screening strategies. PMID- 27270104 TI - Protein undernutrition during development and oxidative impairment in the central nervous system (CNS): potential factors in the occurrence of metabolic syndrome and CNS disease. AB - Mitochondria play a regulatory role in several essential cell processes including cell metabolism, calcium balance and cell viability. In recent years, it has been postulated that mitochondria participate in the pathogenesis of a number of chronic diseases, including central nervous system disorders. Thus, the concept of mitochondrial function now extends far beyond the common view of this organelle as the 'powerhouse' of the cell to a new appreciation of the mitochondrion as a transducer of early metabolic insult into chronic disease in later life. In this review, we have attempted to describe some of the associations between nutritional status and mitochondrial function (and dysfunction) during embryonic development with the occurrence of neural oxidative imbalance and neurogenic disease in adulthood. PMID- 27270105 TI - Haplotype estimation for biobank-scale data sets. AB - The UK Biobank (UKB) has recently released genotypes on 152,328 individuals together with extensive phenotypic and lifestyle information. We present a new phasing method, SHAPEIT3, that can handle such biobank-scale data sets and results in switch error rates as low as ~0.3%. The method exhibits O(NlogN) scaling with sample size N, enabling fast and accurate phasing of even larger cohorts. PMID- 27270106 TI - Selfish drive can trump function when animal mitochondrial genomes compete. AB - Mitochondrial genomes compete for transmission from mother to progeny. We explored this competition by introducing a second genome into Drosophila melanogaster to follow transmission. Competitions between closely related genomes favored those functional in electron transport, resulting in a host-beneficial purifying selection. In contrast, matchups between distantly related genomes often favored those with negligible, negative or lethal consequences, indicating selfish selection. Exhibiting powerful selfish selection, a genome carrying a detrimental mutation displaced a complementing genome, leading to population death after several generations. In a different pairing, opposing selfish and purifying selection counterbalanced to give stable transmission of two genomes. Sequencing of recombinant mitochondrial genomes showed that the noncoding region, containing origins of replication, governs selfish transmission. Uniparental inheritance prevents encounters between distantly related genomes. Nonetheless, in each maternal lineage, constant competition among sibling genomes selects for super-replicators. We suggest that this relentless competition drives positive selection, promoting change in the sequences influencing transmission. PMID- 27270107 TI - Clonal evolution of glioblastoma under therapy. AB - Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors present hypermutation at relapse in highly expressed genes, with a clear mutational signature. We find that 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-beta. Silencing LTBP4 in GBM cells leads to suppression of TGF-beta activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-beta pathway as a potential therapeutic target in GBM. PMID- 27270109 TI - Fast and accurate long-range phasing in a UK Biobank cohort. AB - Recent work has leveraged the extensive genotyping of the Icelandic population to perform long-range phasing (LRP), enabling accurate imputation and association analysis of rare variants in target samples typed on genotyping arrays. Here we develop a fast and accurate LRP method, Eagle, that extends this paradigm to populations with much smaller proportions of genotyped samples by harnessing long (>4-cM) identical-by-descent (IBD) tracts shared among distantly related individuals. We applied Eagle to N ~ 150,000 samples (0.2% of the British population) from the UK Biobank, and we determined that it is 1-2 orders of magnitude faster than existing methods while achieving similar or better phasing accuracy (switch error rate ~ 0.3%, corresponding to perfect phase in a majority of 10-Mb segments). We also observed that, when used within an imputation pipeline, Eagle prephasing improved downstream imputation accuracy in comparison to prephasing in batches using existing methods, as necessary to achieve comparable computational cost. PMID- 27270108 TI - Identification of TMEM230 mutations in familial Parkinson's disease. AB - Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders. The pathogenesis of Parkinson's disease remains largely elusive. Here we report a locus for autosomal dominant, clinically typical and Lewy body-confirmed Parkinson's disease on the short arm of chromosome 20 (20pter p12) and identify TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. Disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, with implications for understanding the pathogenic mechanism of Parkinson's disease and for developing rational therapies. PMID- 27270110 TI - Plasma concentrations of coffee polyphenols and plasma biomarkers of diabetes risk in healthy Japanese women. AB - Coffee consumption has been reported to reduce the risk of type 2 diabetes in experimental and epidemiological studies. This anti-diabetic effect of coffee may be attributed to its high content in polyphenols especially caffeic acid and chlorogenic acid. However, the association between plasma coffee polyphenols and diabetic risks has never been investigated in the literature. In this study, fasting plasma samples were collected from 57 generally healthy females aged 38 73 (mean 52, s.d. 8) years recruited in Himeji, Japan. The concentrations of plasma coffee polyphenols were determined by liquid chromatography coupled with mass tandem spectrometer. Diabetes biomarkers in the plasma/serum samples were analysed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman's correlation coefficients. The results showed that plasma chlorogenic acid exhibited negative associations with fasting blood glucose, glycated hemoglobin and C-reactive protein, whereas plasma total coffee polyphenol and plasma caffeic acid were weakly associated with these biomarkers. Our preliminary data support previous findings that coffee polyphenols have anti diabetic effects but further replications with large samples of both genders are recommended. PMID- 27270111 TI - Predictive validity of a brief outpatient neuropsychological battery in individuals 1-25 years post traumatic brain injury. AB - OBJECTIVE: The purpose of this research was to examine the predictive validity of a brief, outpatient neuropsychological battery relative to concurrent functional outcomes 1-25 years post traumatic brain injury. METHOD: A cross-sectional analysis from an archival database. Participants were 377 persons aged 16-85, 1 25 years post mild-complicated to severe traumatic brain injury. Neuropsychological testing and outcome assessment were completed as part of a routine follow-up associated with enrollment in the Southeastern Michigan Traumatic Brain Injury System project, which is a longitudinal research project. Neuropsychological measures included trail making test, California verbal learning test-II (CVLT-II), word generation, Wisconsin card sort testing - 64 card version, digit vigilance test, and Wechsler test of adult reading (WTAR). Outcome measures included the disability rating scale, Glasgow outcome scale extended, supervisor rating scale, and employment. RESULTS: Multiple regression analyses revealed that although demographic and injury characteristics were predictive of level of disability, level of supervision, and employment, neuropsychological test scores including CVLT-II total score for learning trials 1-5; Trails B, and the WTAR represented independent predictors across all outcome measures. CONCLUSIONS: These findings demonstrate the utility of a brief, outpatient battery in prediction of concurrent outcomes up to 25 years post injury. Given the difficulty in receiving full reimbursement for neuropsychological assessment services, the data provide needed empirical support for use of more economical and efficient testing. PMID- 27270112 TI - Handling Regional Variation in Health State Preferences within a Country. AB - BACKGROUND: Health state preferences vary among countries, and country-specific value sets are important in health care reimbursement decisions. When decisions are made at the regional level, regional variation in health state preferences may be important. We propose that shrinkage analysis and Bland-Altman plots can be a helpful way to investigate regional variation. METHODS: The presence of regional variation can be investigated by introducing interactions between regions and the regression coefficients in the scoring algorithm. When variation is present, regional scoring algorithms can be derived through shrinkage analysis. The impact of using regional algorithms in place of the national algorithm can be investigated using simulation and illustrated using Bland-Altman plots. We applied this methodological approach to the Canadian EQ-5D-5L valuation study, which used time-tradeoff (TTO) tasks to elicit health state preferences from 1073 participants from 4 regions (Alberta, British Columbia, Ontario, and Quebec). RESULTS: There were statistically significant interactions between the fixed effects of the scoring algorithm and region. On computing regional scoring algorithms and applying them to the EQ-5D-5L health states reported by our population, the mean utility using the Canada-wide scoring algorithm was 0.87 (standard error, 0.0013), compared to 0.85 (0.0013) on using the algorithm for Alberta, 0.80 (0.0013) on using the algorithm for British Columbia, 0.91 (0.0013) for Ontario, and 0.89 (0.0014) for Quebec. CONCLUSIONS: When health care falls under regional jurisdiction, shrinkage estimators can be used to generate regional scoring algorithms for the EQ-5D-5L and Bland-Altman plots used to assess the importance of regional variation in health state preferences. Our results suggest that mean health state preferences vary among Canada's regions and make a sizable impact on estimates of population mean utility. PMID- 27270113 TI - Accuracy of the Surgeons' Clinical Prediction of Postoperative Major Complications Using a Visual Analog Scale. AB - BACKGROUND: Although the risk factors that contribute to postoperative complications are well recognized, prediction in the context of a particular patient is more difficult. We were interested in using a visual analog scale (VAS) to capture surgeons' prediction of the risk of a major complication and to examine whether this could be improved. METHODS: The study was performed in 3 stages. In phase I, the surgeon assessed the risk of a major complication on a 100-mm VAS immediately before and after surgery. A quality control questionnaire was designed to check if the VAS was being scored as a linear scale. In phase II, a VAS with 6 subscales for different areas of clinical risk was introduced. In phase III, predictions were completed following the presentation of detailed feedback on the accuracy of prediction of complications. RESULTS: In total, 1295 predictions were made by 58 surgeons in 859 patients. Eight surgeons did not use a linear scale (6 logarithmic, 2 used 4 categories of risk). Surgeons made a meaningful prediction of major complications (preoperative median score 40 mm for complications v. 22 mm for no complication, P < 0.001; postoperative 46 mm v. 21 mm, P < 0.001). In phase I, the discrimination of prediction for preoperative (0.778), postoperative (0.810), and POSSUM (Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity) morbidity (0.750) prediction was similar. Although there was no improvement in prediction with a multidimensional VAS, there was a significant improvement in the discrimination of prediction after feedback (preoperative, 0.895; postoperative, 0.918). CONCLUSION: Awareness of different ways a VAS is scored is important when designing and interpreting studies. Clinical assessment of major complications by the surgeon was initially comparable to the prediction of the POSSUM morbidity score and improved significantly following the presentation of clinically relevant feedback. PMID- 27270114 TI - Client engagement in home and community care services: The client and care coordinator perspective. AB - A recent study of two Community Care Access Centres in Ontario was conducted to look at how clients can be involved in their own care while, at the same time, enhance their experience overall. This article describes that study and looks at ways of developing a new client engagement strategy moving forward. PMID- 27270115 TI - Evolution in models of primary care. PMID- 27270116 TI - Myotonic dystrophy type 1. PMID- 27270117 TI - Back pain in a 59-year-old woman with rheumatoid arthritis. PMID- 27270118 TI - Indigenous leaders call for control of health care. PMID- 27270120 TI - Canada's support lags for research on Zika. PMID- 27270119 TI - Electroacupuncture and splinting versus splinting alone to treat carpal tunnel syndrome: a randomized controlled trial. AB - BACKGROUND: The effectiveness of acupuncture for managing carpal tunnel syndrome is uncertain, particularly in patients already receiving conventional treatments (e.g., splinting). We aimed to assess the effects of electroacupuncture combined with splinting. METHODS: We conducted a randomized parallel-group assessor blinded 2-arm trial on patients with clinically diagnosed primary carpal tunnel syndrome. The treatment group was offered 13 sessions of electroacupuncture over 17 weeks. The treatment and control groups both received continuous nocturnal wrist splinting. RESULTS: Of 181 participants randomly assigned to electroacupuncture combined with splinting (n = 90) or splinting alone (n = 91), 174 (96.1%) completed all follow-up. The electroacupuncture group showed greater improvements at 17 weeks in symptoms (primary outcome of Symptom Severity Scale score mean difference [MD] -0.20, 95% confidence interval [CI] -0.36 to -0.03), disability (Disability of Arm, Shoulder and Hand Questionnaire score MD -6.72, 95% CI -10.9 to -2.57), function (Functional Status Scale score MD -0.22, 95% CI 0.38 to -0.05), dexterity (time to complete blinded pick-up test MD -6.13 seconds, 95% CI -10.6 to -1.63) and maximal tip pinch strength (MD 1.17 lb, 95% CI 0.48 to 1.86). Differences between groups were small and clinically unimportant for reduction in pain (numerical rating scale -0.70, 95% CI -1.34 to 0.06), and not significant for sensation (first finger monofilament test -0.08 mm, 95% CI -0.22 to 0.06). INTERPRETATION: For patients with primary carpal tunnel syndrome, chronic mild to moderate symptoms and no indication for surgery, electroacupuncture produces small changes in symptoms, disability, function, dexterity and pinch strength when added to nocturnal splinting. TRIAL REGISTRATION: Chinese Clinical Trial Register no. ChiCTR-TRC-11001655 (www.chictr.org.cn/showprojen.aspx?proj=7890); subsequently deposited in the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch/Trial2.aspx?TrialID=ChiCTR-TRC-11001655). PMID- 27270121 TI - Curbing transplant tourism: Canadian physicians and the law. PMID- 27270122 TI - Gene Expression-Based Screen for Parkinson's Disease Identifies GW8510 as a Neuroprotective Agent. AB - We carried out a gene expression-based in silico screen in order to identify small molecules with gene-expression profiles that are anticorrelated with a gene expression profile for Parkinson's disease (PD). We identified the cyclin dependent kinase 2/5 (CDK2/5) inhibitor GW8510 as our most significant hit and characterized its effects in rodent MN9D cells and in human neuronal cells derived from induced pluripotent stem cells. GW8510 demonstrated neuroprotective ability in MN9D cells in the presence of 1-methyl-4-phenylpyridium (MPP(+)), a widely used neurotoxin model for Parkinson's disease. In order to delineate the nature and extent of GW8510's neuroprotective properties, we studied GW8510 in human neuronal cells in the context of various mechanisms of cellular stress. We found that GW8510 was protective against small-molecule mitochondrial and endoplasmic reticulum stressors. Our findings illustrate an approach to using small-molecule gene expression libraries to identify compounds with therapeutic potential in human diseases. PMID- 27270123 TI - Culture as a mediator of gene-environment interaction: Cultural consonance, childhood adversity, a 2A serotonin receptor polymorphism, and depression in urban Brazil. AB - Research on gene-environment interaction was facilitated by breakthroughs in molecular biology in the late 20th century, especially in the study of mental health. There is a reliable interaction between candidate genes for depression and childhood adversity in relation to mental health outcomes. The aim of this paper is to explore the role of culture in this process in an urban community in Brazil. The specific cultural factor examined is cultural consonance, or the degree to which individuals are able to successfully incorporate salient cultural models into their own beliefs and behaviors. It was hypothesized that cultural consonance in family life would mediate the interaction of genotype and childhood adversity. In a study of 402 adult Brazilians from diverse socioeconomic backgrounds, conducted from 2011 to 2014, the interaction of reported childhood adversity and a polymorphism in the 2A serotonin receptor was associated with higher depressive symptoms. Further analysis showed that the gene-environment interaction was mediated by cultural consonance in family life, and that these effects were more pronounced in lower social class neighborhoods. The findings reinforce the role of the serotonergic system in the regulation of stress response and learning and memory, and how these processes in turn interact with environmental events and circumstances. Furthermore, these results suggest that gene-environment interaction models should incorporate a wider range of environmental experience and more complex pathways to better understand how genes and the environment combine to influence mental health outcomes. PMID- 27270124 TI - Core-Shell Structured o-LiMnO2@Li2CO3 Nanosheet Array Cathode for High Performance, Wide-Temperature-Tolerance Lithium-Ion Batteries. AB - To develop a high-capacity, high-rate, cycle-stable cathode material has long been the focus for lithium-ion battery (LIB) research. Recently, layer-structured orthorhombic-LiMnO2 (o-LMO) has attracted extensive interest owing to its large discharge capacities. However, poor cycle performance greatly hinders its practical application, especially at high temperatures. Conventional strategies to address this issue often lead to sacrificed rate performance and mostly work at low temperatures. Herein, we report a novel core-shell structured, o LiMnO2@Li2CO3 (o-LMO@Li2CO3) nanosheet array cathode, where the Li2CO3 shell improves cycle performance by preventing o-LMO dissolution in the electrolyte (even at an elevated temperature), the o-LMO core provides high capacities and the nanosheet array architecture ensures rate performance (to the best of our knowledge, this o-LMO nanosheet array architecture is reported for the first time). The above features work synergistically to give well-balanced cycle performance (79% capacity retention at 60 degrees C, 400 cycles), capacity (207 mAh g(-1) at 0.5C) and rate performance (128 mAh g(-1) at 5C) of the o-LMO@ Li2CO3 cathode as well as remarkable full-cell performance (~67% capacity retention for 400 cycles at ~2C, 60 degrees C). Our work demonstrates that the synergistic effect between the o-LMO core, Li2CO3 coating and the nanoarray structure is an effective strategy for developing high-energy/power density, high stability LIB cathodes. PMID- 27270125 TI - Transcriptome sequencing of maraena whitefish (Coregonus maraena). AB - Maraena whitefish (Coregonus maraena, Bloch, 1779) is a high-quality food fish belonging to the family Salmonidae with considerable economic relevance in the Baltic area. Aquaculture of this species is fundamental for its successful conservation and thus sustainable fisheries. Robust fishes obtained from breeding lines build the basis for effective aquaculture. Doubtless, the utilization of transcriptome sequencing and identification of genetic markers contribute to this aim. 454 FLX Titanium Sequencing provided 1.31 million sequence reads representing a first insight into the C. maraena transcriptome. The 454 Newbler Assembly arranged 29,094 contigs with an average length of 798bp. We found a whole series of transcripts highly probably resulting from ancient genome duplication and annotated 2887 different transcripts with an average length of 812bp. Functional annotation obtained a transcript composition predominantly comprising enzyme-coding genes. PMID- 27270126 TI - A transcriptome resource for pharaoh cuttlefish (Sepia pharaonis) after ink ejection by brief pressing. AB - Ink ejection is one of the most important defense mechanisms against external stimuli for pharaoh cuttlefish (Sepia pharaonis). The molecular changes during this process remain unknown. To understand the transcriptome changes after ink ejection by brief pressing, two cDNA libraries of pharaoh cuttlefish, from the inkjet group and control group were sequenced using Illumina HiSeqTM 2000. A total of 9,255,502,440nt bases were obtained and by de novo assembly, 73,298 unigenes were generated, which first provided numerous expressed sequence tags from pharaoh cuttlefish. By comparing the expression levels between the two groups, we identified 7064 up-regulated and 2024 down-regulated genes after ink ejection. These differentially-expressed genes included genes related to immunity, cancer, and blood coagulation, which indicated the various effects after ink ejection by brief pressing. These results provide new valuable resources for functional genomic and genetic studies on pharaoh cuttlefish. PMID- 27270127 TI - Cyclovirus Vietnam DNA in immunodeficient patients. AB - BACKGROUND: Cyclovirus Vietnam (CyCV-VN) is a CyCV detected in 2013 from cerebrospinal fluid (CSF) samples of patients with neurological disorders. Information on prevalence, pathogenesis and disease association of CyCV-VN is still very patchy. OBJECTIVES AND STUDY DESIGN: In this study, we have used a PCR assay targeting the Rep gene to investigate the prevalence of CyCV-VN infection in blood and CSF samples of 346 Italian subjects. RESULTS: Overall, 7% of blood samples were positive for CyCV-VN while the virus was not detected in any of the CSF samples. The prevalence of CyCV-VN was relatively high in HIV positive patients (21%), modest in patients with HBV or HCV infection (6%), and low in transplant recipient patients (2%). Positive patients showed low levels of CyCV VN viremia. The virus was not detected in serum samples from healthy individuals. Longitudinal analysis of serum samples obtained from selected patients showed a stable or transient presence of circulating CyCV-VN. CONCLUSIONS: The present study is the first to demonstrate CyCV-VN DNA circulation in Italy and to cast light on some biological aspects of this novel virus of men. PMID- 27270128 TI - Nonstructural protein (NS1) of human parvovirus B19 stimulates host innate immunity and blunts the exogenous type I interferon signaling in vitro. AB - B19 virus is a non-enveloped DNA virus and belongs to the family of parvoviridae. There are two large open reading frames (ORFs), nonstructural protein (NS1) and two capsid proteins (VP1 and VP2). Host innate immune responses form the first line of defense against many pathogen invasion. How B19 virus, especially its encoded viral proteins interacts with host innate immune system remains unknown. In this study we aim to investigate the effect of NS1 on the host innate immune response and exogenous type I IFN signaling. Here we found that the type I IFN can be stimulated by NS1. Interestingly, NS1 also plays an important role in inhibiting the exogenous type I IFN signaling at p-STAT1, ISRE and ISGs levels. We concluded that NS1 may play pivotal role in evading the host immune surveillance. Our data shed novel light on the pathogenesis of B19 viral infection and virus evasion strategies. PMID- 27270129 TI - Porcine deltacoronavirus: Overview of infection dynamics, diagnostic methods, prevalence and genetic evolution. AB - Porcine deltacoronavirus (PDCoV) was first reported in Hong Kong, China in 2012 and reported in United States swine in February 2014. PDCoV has subsequently been detected in South Korea, mainland China, and Thailand. PDCoV has been experimentally confirmed to cause diarrhea in inoculated pigs and need to be differentially diagnosed from porcine epidemic diarrhea virus and transmissible gastroenteritis virus in the field. Rapid diagnosis is critical for the implementation of efficient control strategies against PDCoV. Developing high quality diagnostic methods and understanding PDCoV infection dynamics to collect appropriate specimens at the appropriate time window are important to obtain reliable diagnostic results. Among the virological methods, PDCoV-specific RT-PCR remains the method of choice for the detection of PDCoV; immunohistochemistry combined with hematoxylin and eosin staining has also been commonly used to examine histopathological lesions caused by PDCoV. Serological assays can provide information about previous exposure to PDCoV and also determine antibody responses to infection or vaccination. Prevalence of PDCoV is lower compared to that of PEDV. However, among PDCoV-positive samples, co-infection with other enteric pathogen e.g. PEDV is common. It is also important to understand molecular epidemiology of PDCoV and genetic relationships of global PDCoVs. This review discusses PDCoV infection dynamics and appropriate sample collection for diagnostic testing, the commonly used virological and serological methods for PDCoV diagnosis, prevalence and genetic evolution of PDCoVs. PMID- 27270136 TI - Breznakia blatticola gen. nov. sp. nov. and Breznakia pachnodae sp. nov., two fermenting bacteria isolated from insect guts, and emended description of the family Erysipelotrichaceae. AB - Two novel, obligately anaerobic Firmicutes from the family Erysipelotrichaceae were isolated from the intestinal tracts of a cockroach (strain ErySL, Shelfordella lateralis) and a scarab beetle larva (strain Pei061, Pachnoda ephippiata). Phylogenetic analysis indicated that the strains belong to a monophyletic group of hitherto uncultured bacteria from insect guts that are only distantly related to any described species (<90% 16S rRNA gene sequence similarity). Ultrastructural analysis revealed a Gram-positive cell envelope and, in the case of strain ErySL, a wide electron-lucent space between the cytoplasmic membrane and cell wall. In older cultures, cells formed pleomorphic rods with a thicker peptidoglycan layer. Both strains were obligately anaerobic and fermented glucose to formate, ethanol, and acetate as major products, but strain Pei061 tolerated up to 1% oxygen in the headspace. The same type of metabolism was observed with Erysipelothrix inopinata, except that the latter grew, albeit poorly, even under air. However, previous claims of a microaerophilic or facultatively anaerobic metabolism in the genus Erysipelothrix could not be substantiated. Based on phenotypic and phylogenetic evidence, we propose to classify the isolates as members of a new genus, Breznakia blatticola gen. nov. sp. nov. and Breznakia pachnodae sp. nov., with strain ErySL(T) (=DSM 28867(T)=JCM 30190(T)) and strain Pei061(T) (=DSM 16784(T)=JCM 30191(T)) as type strains, and provide an emended description of the family Erysipelotrichaceae. PMID- 27270137 TI - Cost effectiveness of meniscal allograft for torn discoid lateral meniscus in young women. AB - OBJECTIVE: A discoid meniscus is more prone to tears than a normal meniscus. Patients with a torn discoid lateral meniscus are at increased risk for early onset osteoarthritis requiring total knee arthroplasty (TKA). Optimal management for this condition is controversial given the up-front cost difference between the two treatment options: the more expensive meniscal allograft transplantation compared with standard partial meniscectomy. We hypothesize that meniscal allograft transplantation following excision of a torn discoid lateral meniscus is more cost-effective compared with partial meniscectomy alone because allografts will extend the time to TKA. METHODS: A decision analytic Markov model was created to compare the cost effectiveness of two treatments for symptomatic, torn discoid lateral meniscus: meniscal allograft and partial meniscectomy. Probability estimates and event rates were derived from the scientific literature, and costs and benefits were discounted by 3%. One-way sensitivity analyses were performed to test model robustness. RESULTS: Over 25 years, the partial meniscectomy strategy cost $10,430, whereas meniscal allograft cost on average $4040 more, at $14,470. Partial meniscectomy postponed TKA an average of 12.5 years, compared with 17.30 years for meniscal allograft, an increase of 4.8 years. Allograft cost $842 per-year-gained in time to TKA. CONCLUSION: Meniscal allografts have been shown to reduce pain and improve function in patients with discoid lateral meniscus tears. Though more costly, meniscal allografts may be more effective than partial meniscectomy in delaying TKA in this model. Additional future long term clinical studies will provide more insight into optimal surgical options. PMID- 27270138 TI - Sexually acquired hepatitis C virus infection: a review. AB - Sexually acquired hepatitis C virus (HCV) infection remains a public health problem, with significant disease burden primarily in HIV-positive men who have sex with men (MSM). Over the past decades, the epidemic of sexually transmitted HCV infection has continued to expand and the epidemiology of HCV in HIV has changed significantly. In the post-combination antiretroviral therapy era, sexual network characteristics within the specific core group of MSM with increased sexual risk behaviours, including serosorting on the basis of HIV-positive status and intense mucosally traumatic sexual practices, confer increased HCV acquisition and transmission. This review summarizes the current epidemiology of sexually acquired HCV infection and the clinical and immunological contexts of acute HCV infection, and describes the biological, social, and behavioural factors that have facilitated permucosal transmission of HCV in MSM. While the advent of direct-acting antivirals has improved treatment responses significantly, sexually transmitted HCV reinfections occur in a substantial proportion of HIV-positive MSM following clearance of a primary infection. Effective strategies and preventive interventions that are tailored to the MSM communities to facilitate the control of sexually acquired HCV infection cannot be overemphasized. PMID- 27270139 TI - Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems. AB - Sorption is a key factor in determining the persistence, attenuation and bioavailability of sediment-associated contaminants. However, our understanding of the sorption behaviour of pharmaceuticals in sediments is poor. In this study, we investigated the sorption behaviour of a diverse set of pharmaceuticals in a range sediment types. Sorption affinity of pharmaceuticals for all sediments was found to increase in the order mefenamic acid9 showed relatively good outcomes. We performed the operations safely in patients who were on antithrombotic therapy or had a systemic bleeding tendency pre-injury. Endoscopic hematoma evacuation via a small craniotomy is a safe and minimally invasive procedure in patients older than 65 years with comorbidities. PMID- 27270140 TI - Horizontal gene transfer events reshape the global landscape of arm race between viruses and homo sapiens. AB - Horizontal gene transfer (HGT) drives the evolution of recipient organism particularly if it provides a novel function which enhances the fitness or its adaption to the environment. Virus-host co-evolution is attractive for studying co-evolutionary processes, since viruses strictly replicate inside of the host cells and thus their evolution is inexorably tangled with host biology. HGT, as a mechanism of co-evolution between human and viruses, has been widely documented, however, the roles HGT play during the interaction between human and viruses are still in their infancy. In this study, we performed a comprehensive analysis on the genes horizontally transferred between viruses and their corresponding human hosts. Our study suggests that the HGT genes in human are predominantly enriched in immune related GO terms while viral HGT genes are tend to be encoded by viruses which promote the invasion of immune system of hosts. Based on our results, it gives us a hint about the evolution trajectory of HGT events. Overall, our study suggests that the HGT between human and viruses are highly relevant to immune interaction and probably reshaped the arm race between hosts and viruses. PMID- 27270141 TI - High-throughput screening of filamentous fungi using nanoliter-range droplet based microfluidics. AB - Filamentous fungi are an extremely important source of industrial enzymes because of their capacity to secrete large quantities of proteins. Currently, functional screening of fungi is associated with low throughput and high costs, which severely limits the discovery of novel enzymatic activities and better production strains. Here, we describe a nanoliter-range droplet-based microfluidic system specially adapted for the high-throughput sceening (HTS) of large filamentous fungi libraries for secreted enzyme activities. The platform allowed (i) compartmentalization of single spores in ~10 nl droplets, (ii) germination and mycelium growth and (iii) high-throughput sorting of fungi based on enzymatic activity. A 10(4) clone UV-mutated library of Aspergillus niger was screened based on alpha-amylase activity in just 90 minutes. Active clones were enriched 196-fold after a single round of microfluidic HTS. The platform is a powerful tool for the development of new production strains with low cost, space and time footprint and should bring enormous benefit for improving the viability of biotechnological processes. PMID- 27270144 TI - [A Case of ECA-MCA Double Anastomoses for Hemorrhagic Type of Twig-Like MCA]. AB - Herein, we describe the case of a superficial temporal artery(STA)- and occipital artery (OA)-middle cerebral artery (MCA) double anastomoses that we performed to treat a hemorrhagic twig-like MCA. A 55-year-old man presented to our hospital for investigation of an incidentally identified left MCA occlusion. Left cerebral angiography revealed a twig-like MCA. The (123)I-IMP-single photon emission computed tomography( SPECT) demonstrated no reduction in the cerebral blood flow (CBF), so the patient was initially observed with no treatment. Three months later, he was readmitted with a disturbance of consciousness. The cranial computed tomography revealed a subcortical hemorrhage in the left frontotemporal region and a subdural hematoma. The hematoma was removed via emergency craniotomy. The abnormal vessels were identified and resected, but the parietal branch of the STA was damaged during the skin incision. The histological examination did not reveal the marked fibrous thickening of the intima or wavy internal elastic lamina typically seen with Moyamoya disease. Six months after the initial surgery, a STA-MCA bypass surgery was planned to prevent a future hemorrhage by reducing the hemodynamic overload of the twig-like MCA and improving the cerebral ischemia in the MCA territory that was detected on the preoperative SPECT. However, the parietal branch of the left STA had been injured during the first operation, so we performed a double anastomoses to the MCA using the frontal branch of the STA and the OA. The patient's postoperative course was uneventful and he was discharged 2 weeks after surgery. The follow-up study performed 1 year postoperatively demonstrated no evidence of cerebral infarction and revealed an improvement in the resting CBF and vascular reactivity in the left cerebral hemisphere. No subsequent cerebrovascular events have occurred in this patient during the 7 years since the double anastomoses surgery. Direct bypass for flow conversion from the internal carotid artery to the external carotid artery can be an indispensable treatment for patients with a hemorrhagic twig-like MCA. PMID- 27270145 TI - [A Case of an Adrenocorticotropic Hormone-Producing Pituitary Adenoma Removed via Electromagnetic-Guided Neuroendoscopy]. AB - The use of navigation systems is safe and reliable for neurological surgery. We performed endoscopic transsphenoidal surgery to totally resect an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma associated with oculomotor nerve palsy. A 70-year-old woman developed right ptosis 4 months before admission. She developed anisocoria 2 months later and was referred to the department of neurology from clinic. Brain magnetic resonance imaging(MRI)showed an intrasellar tumor that partially invaded the right cavernous sinus, and she was then referred to our department. She exhibited a round face ("moon face") and central obesity. Laboratory test results showed a high urinary cortisol level and high serum ACTH level, and neither the serum cortisol nor ACTH level was suppressed by a low-dose dexamethasone test. We performed transsphenoidal surgery using high-dimensional endoscopy under electromagnetic navigation. The tumor invading the cavernous sinus was visualized via endoscopy and confirmed on navigation using a flexible needle probe. Postoperative MRI showed total removal of the tumor, and the serum ACTH level recovered to the normal range. The patient's right oculomotor palsy resolved within 1 week postoperatively. In summary, electromagnetic navigation was useful for total resection of a pituitary tumor invading the cavernous sinus, contributing to normalization of the ACTH level and improvement in neurological symptoms. PMID- 27270146 TI - [Pineal Parenchymal Tumor with Marked Cytologic Pleomorphism: Is there a Correlation with the Malignancy Grade?]. AB - INTRODUCTION: In benign pineal parenchymal tumors (PPTs), namely, pineocytoma(PC)and PPT of intermediate differentiation (PPTID), cytologic pleomorphism has occasionally been found;however, it is controversial as to whether the presence of pleomorphic cells leads to upgrading of tumors. We experienced a rare case of pleomorphic PPT in an elderly woman and compared it with a retrospective series of 12 PPTs (PC:3, PPTID:6, pineoblastoma[PB]:3)to evaluate the correlation between pleomorphism and the malignancy grade. CASE AND MATERIALS: A 76-year-old woman presented with gradual cognitive deterioration and gait disturbance. Gadolinium-enhanced magnetic resonance imaging(Gd-MRI)revealed a small, enhanced tumor in the pineal gland with marked hydrocephalus. Endoscopic tumor biopsy and third ventriculostomy were performed simultaneously. The tumor was soft, pinkish, and slightly hemorrhagic. After the biopsy, the patient underwent gamma knife radiosurgery. PATHOLOGICAL FINDINGS: The PPT presented with areas of tumor cells forming pineocytomatous rosettes and areas of giant and multinucleated cells with hyperchromatic nuclei. Neither mitosis nor necrosis was observed. The tumor cells were positive for synaptophysin(SYN)and neurofilament(NF), but negative for glial fibrillary acidic protein(GFAP)and oligodendrocyte lineage transcription factor 2 (Olig2). The MIB-1 labeling index(LI)was 8.1%. There was no difference in the MIB-1 LI between pleomorphic and non-pleomorphic areas. All the 12 PPTs were immunopositive for the neuronal markers SYN and NF. The MIB-1 LI was 0% in PC, 3.5% in PPTID, and 10.5% in PB. The proliferative potential was correlated with the WHO grade. From these findings, the final diagnosis of this pleomorphic case was PPTID grade II, not PC, because the MIB-1 LI was relatively high, even though some tumor cells were forming pineocytomatous rosettes. CONCLUSION: Although cytologic pleomorphism in PPTs is generally considered not to be correlated with the malignancy grade, the final pathological diagnosis should be determined while considering the proliferative potential. PMID- 27270147 TI - [A Case of Carotid Free-Floating Thrombus Treated by Carotid Ultrasonography Guided Endovascular Approach]. AB - We experienced a case of carotid free-floating thrombus treated by carotid ultrasonography-guided endovascular approach. A 63-year-old man was brought to our hospital with the chief complaint of sudden onset left hemiplegia. MRI revealed acute infarction of the right MCA territory due to the right M1 occlusion. Carotid ultrasonography showed a pedunculated, polypoid mobile plaque floating with the cardiac beat. We attempted ultrasonography-guided endovascular treatment. Under proximal balloon protection, the floating plaque was successfully aspirated into the Penumbra aspiration catheter. Carotid stent was also placed to stabilize the residual pedicle of the plaque. Aspirated plaque was identified as fresh thrombus by pathological examination. Carotid ultrasonography guided endovascular approach was effective for getting the picture of real-time dynamics of the carotid FFT. PMID- 27270148 TI - [A Dumbbell-Type Thoracic Spinal Lipoma: A Case Report]. AB - Spinal lipomas are rare, accounting for less than 1% of all spinal tumors. Most are associated with spinal dysraphism. Spinal lipomas without spinal dysraphism are uncommon;they are typically subpial tumors. Some tumors are located both inside and outside the dura mater (so-called "dumbbell-type"). Herein, we report a patient with a dumbbell-type thoracic spinal lipoma. A man in his 50's complained of progressive gait disturbance, dysesthesia in his left leg, and hyperesthesia in his right leg. His symptoms were worsened by exercise. CT and MRI revealed a thoracic spinal lipoma extending from the spinal cord to the intervertebral foramen at the Th 6-8 level. He underwent partial tumor removal and untethering. Postoperatively he reported gradual symptom abatement. Dumbbell type spinal lipomas are very rare. Besides partial removal of the tumor, untethering should be considered when symptoms are associated with tethering of the spinal cord. PMID- 27270149 TI - [Successful Treatment of Repeated Bilateral Middle Cerebral Artery Occlusion by Performing Mechanical Thrombectomy in a Patient with Trousseau Syndrome]. AB - We report a patient with Trousseau syndrome who presented with repeated acute middle cerebral artery (MCA) occlusion, which was successfully treated by performing mechanical thrombectomy. A 66-year-old man with a lung lesion and abdominal lymph node swelling experienced a sudden onset of left hemiparesis. Magnetic resonance angiography (MRA) revealed a right MCA occlusion. Perfusion weighted imaging revealed reduced cerebral blood flow in the right MCA territory. Complete recanalization of the occluded vessel was achieved by performing mechanical thrombectomy, and his symptoms remarkably disappeared. Twenty days after the procedure, he experienced right hemiparesis and total aphasia. MRA revealed a left MCA occlusion, which was located on the contralateral side of the first occlusion. The second mechanical thrombectomy was successfully performed, and complete recanalization was successfully achieved. Right hemiparesis improved after the procedure. Histological examination of the retrieved clots revealed coagulated fibrin and platelets. Cytodiagnosis of pleural effusion revealed adenocarcinoma, and he was diagnosed with lung adenocarcinoma and cancerous pleurisy. Trousseau syndrome was the presumed primary cause of the patient's tendency for thrombogenesis. To the best of our knowledge, there were no reports regarding the repeated use of mechanical thrombectomy for patients with bilateral MCA occlusion caused by Trousseau syndrome. Neuroendovascular therapy can offer good neurological outcomes even in patients with malignant lesions. PMID- 27270150 TI - [Unilateral Posterior Reversible Encephalopathy Syndrome after Ventriculo Peritoneal Shunt for Normal Pressure Hydrocephalus Following Subarachnoid Hemorrhage: A Case Report]. AB - The patient, a 79-year-old man, experienced a Hunt & Kosnik grade IV subarachnoid hemorrhage, presenting with sudden-onset coma and severe left hemiplegia. We performed cranial clipping surgery for a ruptured aneurysm on the right middle cerebral artery the same day. Post-operative recovery proceeded smoothly, with gradual improvements in disturbed consciousness and left hemiplegia. Three weeks post-operation, CT revealed low-density areas in the right frontal and temporal lobe, believed to be due to subarachnoid hemorrhage, as well as hydrocephaly. We then performed a lumbo-peritoneal (L-P) shunt for the hydrocephaly. Two months later, the patient experienced shunt occlusion, and we performed a ventriculo peritoneal (V-P) shunt revision (pressure: 6 cm H(2)O). Headaches, severe decline in cognitive function, and worsened left hemiplegia were observed seven weeks post-shunt revision. Cranial CT revealed widespread low-density areas in right posterior cerebral white matter. We suspected unilateral posterior reversible encephalopathy syndrome (PRES) after performing cranial MRI and cerebral angiography. Increasing the set pressure of the shunt improved the symptoms and radiographic findings. PRES is typically bilateral, and unilateral incidents are rare. This is the first report of unilateral PRES secondary to shunt operation. Its unilaterality appears to have been caused by unilateral brain damage or adhesions to the brain surface from the subarachnoid cerebral hemorrhage. Overdrainage post-shunt can also induce PRES. Diagnosis of PRES is more difficult in unilateral cases;practitioners must keep PRES in mind as a rare complication post-shunt operation. PMID- 27270151 TI - [A Case of Ruptured Internal Carotid-Posterior Communicating Artery Aneurysm Associated with Acute Subdural Hematoma, Extending from the Interhemispheric Space to the Posterior Fossa]. AB - A 69-year-old woman was admitted to our hospital because of a sudden severe headache without a history of head trauma. CT and MRI revealed an acute subdural hematoma (ASDH) extending from the right interhemispheric space to the posterior fossa bilaterally, with a small amount of subarachnoid hemorrhage that was predominantly localized to the left side of the basal cistern. CT angiogram demonstrated a long protruding ruptured aneurysm at the junction of the right internal carotid and posterior communicating arteries (IC/PC AN) with a posteroinferior projection, associated with a small bleb located near the tentorial edge close to the ipsilateral posterior clinoid process, for which she received clipping surgery. Though rare, IC/PC AN could cause pure or nearly pure ASDH in the above-mentioned distribution. Therefore, in patients with such ASDH, especially without a history of head injury or precise information regarding the situation at the time of onset, urgent imaging evaluation and early intervention are essential to prevent devastating re-rupture events. PMID- 27270152 TI - Tailoring the Microstructure of a Solid Oxide Fuel Cell Anode Support by Calcination and Milling of YSZ. AB - In this study, the effects of calcination and milling of 8YSZ (8 mol% yttria stabilized zirconia) used in the nickel-YSZ anode on the performance of anode supported tubular fuel cells were investigated. For this purpose, two different types of cells were prepared based on a Ni-YSZ/YSZ/Nd2NiO4+delta-YSZ configuration. For the anode preparation, a suspension was prepared by mixing NiO and YSZ in a ratio of 65:35 wt% (Ni:YSZ 50:50 vol.%) with 30 vol.% graphite as the pore former. As received Tosoh YSZ or its calcined form (heated at 1500 degrees C for 3 hours) was used in the anode support as the YSZ source. Electrochemical results showed that optimization of the fuel electrode microstructure is essential for the optimal distribution of gas within the support of the cell, especially under electrolysis operation where the performance for an optimized cell (calcined YSZ) was enhanced by a factor of two. In comparison with a standard cell (containing as received YSZ), at 1.5 V and 800 degrees C the measured current density was -1380 mA cm(-2) and -690 mA cm(-2) for the cells containing calcined and as received YSZ, respectively. The present study suggests that the anode porosity for improved cell performance under SOEC is more critical than SOFC mode due to more complex gas diffusion under electrolysis mode where large amount of steam needs to be transfered into the cell. PMID- 27270154 TI - National Psoriasis Foundation: a patient-centric approach to improve access to psoriatic disease treatment. AB - Psoriasis and psoriatic arthritis are serious autoimmune diseases requiring lifelong management and support. Uncontrolled psoriatic disease wields a significant impact on the lives of those affected, resulting in lowered quality of life, disability, depression, increased risk of related illnesses (eg, heart disease, diabetes), and early mortality. In National Psoriasis Foundation (NPF) surveys, roughly two-thirds of patients with psoriasis and/or psoriatic arthritis said their disease made them feel angry, frustrated, and/or helpless, and more than half said psoriasis interfered with their ability to enjoy life. The economic burden of psoriasis is equally daunting, and NPF surveys consistently report cost to be a significant barrier to treatment. This challenge is one of many reasons the NPF launched an aggressive strategic plan in 2014 intended to: 1) cut in half the number of patients who report that their condition is a problem in everyday life, 2) increase by 50% the number of patients receiving the right treatment, and 3) double the number of healthcare providers effectively managing patients with psoriasis and psoriatic arthritis. The NPF has launched several large-scale projects-including the development and implementation of solutions that reduce high out-of-pocket costs-intended to significantly increase the number of people with psoriatic disease who are effectively managing their condition. PMID- 27270155 TI - Accessing the cure: helping patients with hepatitis C overcome barriers to care. AB - Hepatitis C virus (HCV) is an illustrative example of the dilemma faced by patients in the American healthcare landscape: HCV is a chronic, progressive disease for which a cure exists, but at such high prices that cost-sharing innovations create significant barriers to care, treatment, and cure. Previous HCV treatments were ineffective and had a wide range of severe side effects, so much so, that both patients and their providers chose to wait for newer and more effective options. Yet, once these options became available, cost-sharing mechanisms, such as plan premiums, deductibles, co-payments, and coinsurance, created barriers to treatment, producing a large pool of patients infected with HCV who are willing but unable to access a cure. In response, advocacy organizations like the National Viral Hepatitis Roundtable and Project Inform have developed innovative strategies to improve access to HCV care and treatment. PMID- 27270156 TI - An introduction to the Patient Access Network Foundation and AJMC collaborative supplement. PMID- 27270157 TI - High cost sharing and specialty drug initiation under Medicare Part D: a case study in patients with newly diagnosed chronic myeloid leukemia. AB - OBJECTIVES: Specialty drugs often offer medical advances but are frequently subject to high cost sharing. This is particularly true with Medicare Part D, where after meeting a deductible, patients without low-income subsidies (non-LIS) typically face 25% to 33% coinsurance (initial coverage phase with "specialty tier" cost sharing), followed by ~50% coinsurance (coverage gap phase), and then 5% coinsurance (catastrophic phase). Yet, no studies have examined the impact of such high cost sharing on specialty drug initiation under Part D. Oral tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it an apt case study. STUDY DESIGN: A retrospective claims based analysis utilizing 2011 to 2013 100% Medicare claims. METHODS: TKI initiation rates and time to initiation were compared between fee-for-service non LIS Part D patients newly diagnosed with CML and their LIS counterparts who faced nominal cost sharing of <= $5. RESULTS: The first 30-day TKI fill "straddled" benefit phases, for a mean out-of-pocket cost of $2600 or more for non-LIS patients. Non-LIS patients were less likely than LIS patients to have a TKI claim within 6 months of diagnosis (45.3% vs 66.9%; P < .001) and those initiating a TKI took twice as long to fill it (mean = 50.9 vs 23.7 days; P < .001). Cox regressions controlling for sociodemographic, clinical, and plan characteristics confirmed descriptive findings (hazard ratio, 0.59; 95% CI, 0.45-0.76). Extensive sensitivity analyses confirmed the robustness of our findings. CONCLUSIONS: High cost sharing was associated with reduced and/or delayed initiation of TKIs. We discuss policy strategies to reduce current financial barriers that adversely impact access to critical therapies under Medicare Part D. PMID- 27270158 TI - The redesign of consumer cost sharing for specialty drugs at the California Health Insurance Exchange. AB - This paper describes the redesign of health benefits at Covered California-the nation's largest health insurance exchange, which covers 1.3 million individuals, and its benefit designs extending to hundreds of thousands more enrollees through insurance products sold outside the exchange-with respect to specialty drugs for the 2016 enrollment year. The catalyst for benefit redesign came from advocacy organizations representing patients suffering from HIV, multiple sclerosis, epilepsy, hepatitis C, and other chronic conditions. The first component of the benefit redesign creates a separate deductible for pharmaceutical expenditures, with a commensurate reduction in the deductible for other (medical) expenditures. The second component requires health plans to assign at least 1 specialty drug for each therapeutic class to a nonspecialty tier, offering patients a treatment option for which they are not exposed to coinsurance. The third component imposes a monthly payment limit of $250 for each specialty drug prescription, thereby buffering patients using these drugs against the $6250 individual, or $13,500 family, annual medical payment limit. The pharmacy deductible and monthly out-of pocket payment limit are substantially lower for low-income enrollees in the subsidized silver-tier products. The Covered California redesign indicates that patients can be shielded from the most onerous cost-sharing burdens while keeping premiums affordable for the entire enrolled population; however, sustainable access to care requires reductions in the underlying cost of new clinical technologies. PMID- 27270159 TI - Practical solutions when facing cost sharing: the American Cancer Society's Health Insurance Assistance Service. AB - The American Cancer Society (ACS) has been a leading voice for healthcare reform and an informed advocate for effective health insurance reforms. Since the implementation of the Affordable Care Act (ACA), the ACS has observed a shift in inquiries to its Health Insurance Assistance Service (HIAS) from individuals seeking coverage, to a growing problem of individuals presenting issues from being underinsured. Underinsured patients with cancer face serious financial challenges due to large co-pays and coinsurance costs. HIAS was created to help these patients identify potential options for insurance coverage while tracking patient trends. The types of calls received by HIAS have been captured as part of an internal database that allows for the analysis of trends and emerging issues. By evaluating several case studies that illustrate common issues faced by underinsured individuals, we identified solutions ranging from exploring financial assistance programs, such as co-pay relief and providing appeal information, to searching for more adequate or affordable insurance options. Additionally, the ACS has worked to find strong partnerships with other nonprofit organizations to aid in cost relief. Although the ACA has made plans available to many patients and their families, the maximum for an individual's in-network out of-pocket costs are still too high for many individuals. New approaches are needed to improve the cost protection of health plans. By documenting access problems faced by patients with cancer, the ACS is better positioned to tell policy makers about the concerns of real patients and work toward policy solutions. PMID- 27270160 TI - The MS Center of Saint Louis: a practice perspective of the impacts of high cost sharing. AB - As treatment for multiple sclerosis (MS) has become increasingly expensive, patients have had to shoulder a greater cost-sharing burden. This case study follows a fictitious patient as she encounters the common cost-related barriers to treatment that have been observed by providers at the MS Center of Saint Louis. Medications, tests to monitor patient safety on medications, physical therapy, occupational therapy, medical equipment, mental health counseling, transportation, and modifications to house or vehicles are all common needs of MS patients that increase their cost burden. The MS Center of Saint Louis provides care management and education to help patients budget for expected expenses and navigate resources for assistance. However, this will ultimately be an unsustainable solution without substantial policy change. PMID- 27270161 TI - In-office dispensing of oral oncolytics: a continuity of care and cost mitigation model for cancer patients. AB - The high cost of cancer therapies continues to lead to questions of affordability for the healthcare system and to patients. Ensuring patient access to oral cancer drugs presents a unique set of challenges due to the significant cost of these novel agents, healthcare/payer policies, and established distribution practices. The National Community Oncology Dispensing Association, Inc (NCODA) is a grassroots, nonprofit organization established by pharmacists who are directly involved at the community practice level in assisting patients with the acquisition of their oral cancer drugs. Community oncology practices that embrace the NCODA Quality Standards are able to provide exceptional patient care by providing direct access to oral cancer drugs through the in-practice dispensary. Patient continuity of care is ensured by allowing practice staff to manage all aspects of drug therapy-from initial dispense to completion of therapy-and in practice dispensing allows for improved patient convenience, safety, and compliance. Practice staff in the dispensary area work directly with patients to address the insurance coverage limitations and financial toxicity of procuring these drugs. Medicare patients are not eligible to take advantage of patient assistance and/or co-pay programs that have been established by pharmaceutical companies. Foundations such as the Patient Access Network Foundation have been established to provide assistance to Medicare patients. This case report focuses on a new dispensary in a moderately sized oncology community practice that prescribes to the NCODA Quality Standards and outlines the processes developed to assist Medicare patients in accessing their oral cancer medications. PMID- 27270162 TI - Programmable DNA Nanosystem for Molecular Interrogation. AB - We describe a self-assembling DNA-based nanosystem for interrogating molecular interactions. The nanosystem contains a rigid supporting dumbbell-shaped frame, a cylindrical central core, and a mobile ring that is coaxial with the core. Motion of the ring is influenced by several control elements whose force-generating capability is based on the transition of single-stranded DNA to double-stranded DNA. These forces can be directed to act in opposition to adhesive forces between the ring and the frame thereby providing a mechanism for molecular detection and interrogation at the ring-frame interface. As proof of principle we use this system to evaluate base stacking adhesion and demonstrate detection of a soluble nucleic acid viral genome mimic. PMID- 27270165 TI - THE CANON - 1. PMID- 27270163 TI - Platelet-Monocyte Aggregates and C-Reactive Protein are Associated with VTE in Older Surgical Patients. AB - Emerging evidence implicates platelets as key mediators of venous thromboembolism (VTE). Nevertheless, the pathways by which platelets and circulating procoagulant proteins synergistically orchestrate VTE remain incompletely understood. We prospectively determined whether activated platelets and systemic procoagulant factors were associated with VTE in 32 older orthopedic surgery patients. Circulating platelet-monocyte aggregates (PMAs), p-selectin expression (P-SEL), and integrin alphaIIbbeta3 activation (PAC-1 binding) were assessed pre operatively and 24 hours post-operatively. The proinflammatory and procoagulant molecule C-reactive protein (CRP), which induces PMA formation in vitro, along with plasma d-dimer and fibrinogen levels were also measured. The primary outcome was VTE occurring within 30 days post-operatively. Overall, 40.6% of patients developed VTE. Patients with VTE had a significant increase in circulating PMAs and CRP post-operatively, compared to those without VTE. Changes in PMA and CRP in VTE patients were significantly correlated (r(2) = 0.536, p = 0.004). In contrast, P-SEL expression and PAC-1 binding, fibrinogen levels, and d-dimers were not associated with VTE. This is the first study to identify that increased circulating PMAs and CRP levels are early markers associated with post-surgical VTE. Our findings also provide new clinical evidence supporting the interplay between PMAs and CRP in patients with VTE. PMID- 27270164 TI - MTHFR gene polymorphisms and methotrexate toxicity in adult patients with hematological malignancies: a meta-analysis. AB - BACKGROUND: MTHFR gene polymorphisms has been shown to be associated with methotrexate (MTX) toxicity in adult hematological malignancies; however, the results remain inconclusive. MATERIALS & METHODS: To examine the role of common MTHFR variants in MTX toxicity prediction, we performed a meta-analysis via identifying relevant studies for quantitative data pooling. RESULTS: Our results showed a significant association between MTHFR C677T polymorphism and increased risk of MTX-induced all-grade (grade 1-4) and severe (grade 3-4) hepatic and gastrointestinal toxicities in Caucasian independent of MTX dosage. MTHFR 677T allele increased risk of severe mucositis and all-grade hematological toxicity. MTHFR A1298C polymorphism was not significantly associated with hepatic and hematological toxicity, whereas perhaps having a protective effect on mucositis and gastrointestinal toxicity. CONCLUSION: MTHFR C677T polymorphism may be a good predictor for MTX toxicity in adult hematological malignancies. PMID- 27270166 TI - The end of stigma? Changes in the social experience of long-term illness, by Gill Green. PMID- 27270167 TI - Anthropology & Medicine. PMID- 27270168 TI - Would Brexit stop the flow of doctors and patients between EU countries? PMID- 27270169 TI - Stimulated infrared thermography applied to differentiate scar tissue from peri scar tissue: a preliminary study. AB - Every human injury leads to a scar formation. The healing process leads to the formation of new tissue: the scar, which is different from the original tissue. This process is influenced by mechanical strength and the local vasculature is modified. The purpose of this study is to show that there are various temperatures between the scar and the peri-scar area associated with the healing process that can be estimated using the thermal infrared camera. In the study, 12 scars were stimulated by cold. Several changes of temperature were observed between scar and peri-scar area for 10 min. Scars appeared significantly colder with a Wilcoxon test (p = 0.01). Results showed that stimulated infrared thermography can be used to monitor the temperature difference between the scar and peri-scar tissue. PMID- 27270170 TI - Soluble fms-like tyrosine kinase 1 promotes angiotensin II sensitivity in preeclampsia. AB - Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and is associated with substantial morbidity for the mother and fetus. Enhanced vasoconstrictor sensitivity and elevations in soluble fms-like tyrosine kinase 1 (sFLT1), a circulating antiangiogenic protein, precede clinical signs and symptoms of preeclampsia. Here, we report that overexpression of sFlt1 in pregnant mice induced angiotensin II sensitivity and hypertension by impairing endothelial nitric oxide synthase (eNOS) phosphorylation and promoting oxidative stress in the vasculature. Administration of the NOS inhibitor l-NAME to pregnant mice recapitulated the angiotensin sensitivity and oxidative stress observed with sFlt1 overexpression. Sildenafil, an FDA-approved phosphodiesterase 5 inhibitor that enhances NO signaling, reversed sFlt1-induced hypertension and angiotensin II sensitivity in the preeclampsia mouse model. Sildenafil treatment also improved uterine blood flow, decreased uterine vascular resistance, and improved fetal weights in comparison with untreated sFlt1-expressing mice. Finally, sFLT1 protein expression inversely correlated with reductions in eNOS phosphorylation in placental tissue of human preeclampsia patients. These data support the concept that endothelial dysfunction due to high circulating sFLT1 may be the primary event leading to enhanced vasoconstrictor sensitivity that is characteristic of preeclampsia and suggest that targeting sFLT1-induced pathways may be an avenue for treating preeclampsia and improving fetal outcomes. PMID- 27270171 TI - Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. AB - BACKGROUND: In some active multiple sclerosis (MS) lesions, a strong immune reaction at the lesion edge may contain growth and thereby isolate the lesion from the surrounding parenchyma. Our previous studies suggest that this process involves opening of the blood-brain barrier in capillaries at the lesion edge, seen on MRI as centripetal contrast enhancement and a colocalized phase rim. We hypothesized that using these features to characterize early lesion evolution will allow in vivo tracking of tissue degeneration and/or repair, thus improving the evaluation of potential therapies for chronic active lesions. METHODS: Centripetally and centrifugally enhancing lesions were studied in 17 patients with MS using 7-tesla MRI. High-resolution, susceptibility-weighted, T1-weighted (before/after gadolinium), and dynamic contrast-enhanced scans were acquired at baseline and months 1, 3, 6, and 12. For each lesion, time evolution of the phase rim, lesion volume, and T1 hypointensity were assessed. In autopsies of 3 progressive MS cases, the histopathology of the phase rim was determined. RESULTS: In centripetal lesions, a phase rim colocalized with initial contrast enhancement. In 12 of 22, this phase rim persisted after enhancement resolved. Compared with centripetal lesions with transient rim, those with persistent rim had less volume shrinkage and became more T1 hypointense between months 3 and 12. No centrifugal lesions developed phase rims at any time point. Pathologically, persistent rims corresponded to an iron-laden inflammatory myeloid cell population at the edge of chronic demyelinated lesions. CONCLUSION: In early lesion evolution, a persistent phase rim in lesions that shrink least and become more T1 hypointense over time suggests that the rim might mark failure of early lesion repair and/or irreversible tissue damage. In later stages of MS, phase rim lesions continue to smolder, exerting detrimental effects on affected brain tissue. TRIAL REGISTRATION: NCT00001248. FUNDING: The Intramural Research Program of NINDS supported this study. PMID- 27270172 TI - GABA interneurons mediate the rapid antidepressant-like effects of scopolamine. AB - Major depressive disorder (MDD) is a recurring psychiatric illness that causes substantial health and socioeconomic burdens. Clinical reports have revealed that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, produces rapid antidepressant effects in individuals with MDD. Preclinical models suggest that these rapid antidepressant effects can be recapitulated with blockade of M1-type muscarinic acetylcholine receptors (M1-AChR); however, the cellular mechanisms underlying activity-dependent synaptic and behavioral responses to scopolamine have not been determined. Here, we demonstrate that the antidepressant-like effects of scopolamine are mediated by GABA interneurons in the medial prefrontal cortex (mPFC). Both GABAergic (GAD67+) interneurons and glutamatergic (CaMKII+) interneurons in the mPFC expressed M1-AChR. In mice, viral-mediated knockdown of M1-AChR specifically in GABAergic neurons, but not glutamatergic neurons, in the mPFC attenuated the antidepressant-like effects of scopolamine. Immunohistology and electrophysiology showed that somatostatin (SST) interneurons in the mPFC express M1-AChR at higher levels than parvalbumin interneurons. Moreover, knockdown of M1-AChR in SST interneurons in the mPFC demonstrated that M1-AChR expression in these neurons is required for the rapid antidepressant-like effects of scopolamine. These data indicate that SST interneurons in the mPFC are a promising pharmacological target for developing rapid-acting antidepressant therapies. PMID- 27270173 TI - Eulogy for the clinical research center. AB - The extramural General Clinical Research Center (GCRC) program has been funded for more than 50 years, first by the National Center for Research Resources, NIH, and more recently as part of the Clinical Translational Science Award (CTSA) program through the newly formed National Center for Advancing Translation Sciences (NCATS). The GCRCs represent the federally funded laboratories that employ a highly trained cadre of research nurses, dietitians, and other support staff and in which generations of clinical investigators trained and performed groundbreaking human studies that advanced medical science and improved clinical care. Without the opportunity for adequate discussion, NCATS has now stopped funding these Research Centers. In this "eulogy," we review the origins and history of the GCRCs, their contributions to the advancement of medicine, and the recent events that have essentially defunded them. We mourn their loss. PMID- 27270174 TI - Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity. AB - Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms involved in the etiology of these defects have not been fully characterized. Previously, we observed PCG-like phenotypes in transgenic mice that lack functional angiopoietin TEK signaling. Herein, we identified rare TEK variants in 10 of 189 unrelated PCG families and demonstrated that each mutation results in haploinsufficiency due to protein loss of function. Multiple cellular mechanisms were responsible for the loss of protein function resulting from individual TEK variants, including an absence of normal protein production, protein aggregate formation, enhanced proteasomal degradation, altered subcellular localization, and reduced responsiveness to ligand stimulation. Further, in mice, hemizygosity for Tek led to the formation of severely hypomorphic Schlemm's canal and trabecular meshwork, as well as elevated IOP, demonstrating that anterior chamber vascular development is sensitive to Tek gene dosage and the resulting decrease in angiopoietin-TEK signaling. Collectively, these results identify TEK mutations in patients with PCG that likely underlie disease and are transmitted in an autosomal dominant pattern with variable expressivity. PMID- 27270175 TI - Phosphorylation state-dependent modulation of spinal glycine receptors alleviates inflammatory pain. AB - Diminished inhibitory neurotransmission in the superficial dorsal horn of the spinal cord is thought to contribute to chronic pain. In inflammatory pain, reductions in synaptic inhibition occur partially through prostaglandin E2- (PGE2 ) and PKA-dependent phosphorylation of a specific subtype of glycine receptors (GlyRs) that contain alpha3 subunits. Here, we demonstrated that 2,6-di-tert butylphenol (2,6-DTBP), a nonanesthetic propofol derivative, reverses inflammation-mediated disinhibition through a specific interaction with heteromeric alphabetaGlyRs containing phosphorylated alpha3 subunits. We expressed mutant GlyRs in HEK293T cells, and electrophysiological analyses of these receptors showed that 2,6-DTBP interacted with a conserved phenylalanine residue in the membrane-associated stretch between transmembrane regions 3 and 4 of the GlyR alpha3 subunit. In native murine spinal cord tissue, 2,6-DTBP modulated synaptic, presumably alphabeta heteromeric, GlyRs only after priming with PGE2. This observation is consistent with results obtained from molecular modeling of the alpha-beta subunit interface and suggests that in alpha3betaGlyRs, the binding site is accessible to 2,6-DTBP only after PKA dependent phosphorylation. In murine models of inflammatory pain, 2,6-DTBP reduced inflammatory hyperalgesia in an alpha3GlyR-dependent manner. Together, our data thus establish that selective potentiation of GlyR function is a promising strategy against chronic inflammatory pain and that, to our knowledge, 2,6-DTBP has a unique pharmacological profile that favors an interaction with GlyRs that have been primed by peripheral inflammation. PMID- 27270177 TI - Clinical responses with T lymphocytes targeting malignancy-associated kappa light chains. AB - BACKGROUND: Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor (CAR) shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan-B cell marker, also depletes normal B cells and causes severe hypogammaglobulinemia. Here, we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction. We generated a CAR that is specific for the kappa light chain (kappa.CAR) and therefore recognizes kappa restricted cells and spares the normal B cells expressing the nontargeted lambda light chain, thus potentially minimizing humoral immunity impairment. METHODS: We conducted a phase 1 clinical trial and treated 16 patients with relapsed or refractory kappa+ non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) or multiple myeloma (MM) with autologous T cells genetically modified to express kappa.CAR (kappa.CARTs). Other treatments were discontinued in 11 of the 16 patients at least 4 weeks prior to T cell infusion. Six patients without lymphopenia received 12.5 mg/kg cyclophosphamide 4 days before kappa.CART infusion (0.2 * 108 to 2 * 108 kappa.CARTs/m2). No other lymphodepletion was used. RESULTS: kappa.CART expansion peaked 1-2 weeks after infusion, and cells remained detectable for more than 6 weeks. Of 9 patients with relapsed NHL or CLL, 2 entered complete remission after 2 and 3 infusions of kappa.CARTs, and 1 had a partial response. Of 7 patients with MM, 4 had stable disease lasting 2-17 months. No toxicities attributable to kappa.CARTs were observed. CONCLUSION: kappa.CART infusion is feasible and safe and can lead to complete clinical responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00881920. FUNDING: National Cancer Institute (NCI) grants 3P50CA126752 and 5P30CA125123 and Leukemia and Lymphoma Society (LLS) Specialized Centers of Research (SCOR) grant 7018. PMID- 27270178 TI - Enhanced Visualization of Optimal Cerebral Perfusion Pressure Over Time to Support Clinical Decision Making. AB - OBJECTIVE: Cerebrovascular reactivity can provide a continuously updated individualized target for management of cerebral perfusion pressure, termed optimal cerebral perfusion pressure. The objective of this project was to find a way of improving the optimal cerebral perfusion pressure methodology by introducing a new visualization method. DATA SOURCES: Four severe traumatic brain injury patients with intracranial pressure monitoring. DATA EXTRACTION: Data were collected and pre-processed using ICM+ software. DATA SYNTHESIS: Sequential optimal cerebral perfusion pressure curves were used to create a color-coded maps of autoregulation - cerebral perfusion pressure relationship evolution over time. CONCLUSIONS: The visualization method addresses some of the main drawbacks of the original methodology and might bring the potential for its clinical application closer. PMID- 27270176 TI - p66Shc regulates renal vascular tone in hypertension-induced nephropathy. AB - Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic Ca2+ influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy. PMID- 27270179 TI - Combining Prognostic and Predictive Enrichment Strategies to Identify Children With Septic Shock Responsive to Corticosteroids. AB - OBJECTIVES: Prognostic and predictive enrichment strategies are fundamental tools of precision medicine. Identifying children with septic shock who may benefit from corticosteroids remains a challenge. We combined prognostic and predictive strategies to identify a pediatric septic shock subgroup responsive to corticosteroids. DESIGN: We conducted a secondary analysis of 288 previously published pediatric subjects with septic shock. For prognostic enrichment, each study subject was assigned a baseline mortality probability using the pediatric sepsis biomarker risk model. For predictive enrichment, each study subject was allocated to one of two septic shock endotypes, based on a 100-gene signature reflecting adaptive immunity and glucocorticoid receptor signaling. The primary study endpoint was complicated course, defined as the persistence of two or more organ failures at day 7 of septic shock or 28-day mortality. We used logistic regression to test for an association between corticosteroids and complicated course within endotype. MEASUREMENTS AND MAIN RESULTS: Among endotype B subjects at intermediate to high pediatric sepsis biomarker risk model-based risk of mortality, corticosteroids were independently associated with more than a 10-fold reduction in the risk of a complicated course (relative risk, 0.09; 95% CI, 0.01 0.54; p = 0.007). CONCLUSIONS: A combination of prognostic and predictive strategies based on serum protein and messenger RNA biomarkers can identify a subgroup of children with septic shock who may be more likely to benefit from corticosteroids. Prospective validation of these strategies and the existence of this subgroup are warranted. PMID- 27270180 TI - 4-Aminopyridine, A Blocker of Voltage-Dependent K+ Channels, Restores Blood Pressure and Improves Survival in the Wistar Rat Model of Anaphylactic Shock. AB - OBJECTIVES: Anaphylactic shock is associated with severe hypotension. Potassium channel blockers, such as 4-aminopyridine, induce vasoconstriction. The objective of this study was to test the ability of 4-aminopyridine to restore blood pressure and increase survival in anaphylactic shock. DESIGN: Experimental study. SETTING: Physiology laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Rats were sensitized with ovalbumin (1 mg SC), and anaphylactic shock was induced by IV injection of ovalbumin (1 mg). Experimental groups included non-allergic rats (NA) (n = 6); allergic rats (Controls) (n = 6); allergic rats treated with 4 aminopyridine (4-aminopyridine) (1 mg/kg) (n = 6); and allergic rats treated with epinephrine (EPI) (10 ug/kg) (n = 6). Treatments were administered 1 minute after induction of anaphylactic shock. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure, heart rate, and survival were measured for 60 minutes. Plasma levels of histamine, leukotriene B4, prostaglandin E2, prostaglandin F2, pH, and HCO3 were measured. Mean arterial blood pressure was normal in the NA group; severe hypotension and high mortality were observed in controls; normalization of mean arterial blood pressure, heart rate, and increased survival were observed in 4-aminopyridine and EPI groups. All allergic 4-aminopyridine-treated rats survived after the induction of anaphylactic shock. Histamine level was higher in controls and the 4-aminopyridine group but reduced in the EPI group. Prostaglandin E2 increased in controls and EPI group and decreased in 4 aminopyridine group; prostaglandin F2 increased in controls but decreased in 4 aminopyridine and EPI groups. Leukotriene B4 decreased in 4-aminopyridine and EPI groups. Metabolic acidosis was prevented in the 4-aminopyridine group. CONCLUSIONS: Our data suggest that voltage-dependent K+ channel inhibition with 4 aminopyridine treatment restores blood pressure and increases survival in the Wistar rat model of anaphylactic shock. 4-aminopyridine or related voltage dependent K channel blockers could be a useful additional therapeutic approach to treatment of refractory anaphylactic shock. PMID- 27270181 TI - Imaging in vascular diseases of the lung. AB - PURPOSE OF REVIEW: The present review focuses on the recent developments in the field of pulmonary angiography and perfusion by means of computed tomography and magnetic resonance imaging. RECENT FINDINGS: Computed tomography allows for a detailed analysis of large and small pulmonary vascular pathologies and simultaneously allows for evaluation of the lung parenchyma. Magnetic resonance imaging allows for large and small vessel evaluation as well as noninvasive pressure assessment. Furthermore, recently non-breath-hold contrast-enhanced and noncontrast-enhanced techniques have been developed making magnetic resonance imaging an ideal tool for comprehensive thoracic imaging, even in challenging patients. SUMMARY: Noninvasive imaging using computed tomography and magnetic resonance imaging further increases their value in daily clinical practice when it comes to assessment of large and small pulmonary artery disease. As computed tomography is more easy to use and widely available, it remains the diagnostic modality of choice. However, magnetic resonance imaging is the modality of choice when a comprehensive angiographic and functional assessment is deemed necessary. PMID- 27270182 TI - Does exercise pulmonary hypertension exist? AB - PURPOSE OF REVIEW: The exercise definition of pulmonary hypertension using a mean pulmonary artery pressure threshold of greater than 30 mmHg was abandoned following the 4th World Pulmonary Hypertension Symposium in 2008, as this definition was not supported by evidence and healthy individuals frequently exceed this threshold. Meanwhile, the clinical value of exercise pulmonary hemodynamic testing has also been questioned. RECENT FINDINGS: Recent data support the notion that an abnormal pulmonary hemodynamic response during exercise (or exercise pulmonary hypertension) is associated with symptoms and exercise limitation. Pathophysiologic mechanisms accounting for the development of exercise pulmonary hypertension include increased vascular resistance, excessive elevation in left atrial pressure and/or increased volume of trapped air during exercise, resulting in a steep rise in pulmonary artery pressure relative to cardiac output. Recent evidence suggests that exercise pulmonary hypertension may be defined by a mean pulmonary artery pressure surpassing 30 mmHg together with a simultaneous total pulmonary resistance exceeding 3 WU. SUMMARY: Exercise pulmonary hypertension is a clinically relevant entity and an improved definition has been suggested based on new evidence. Exercise pulmonary hemodynamics may help unmask early or latent disease, particularly in populations that are at high risk for the development of pulmonary hypertension. PMID- 27270183 TI - Impact of non-clinical community-based promotional campaigns on bowel cancer screening engagement: An integrative literature review. AB - OBJECTIVE: This paper reviewed the relationship between non-clinical, client oriented promotional campaigns to raise bowel cancer awareness and screening engagement. METHOD: An integrative literature review using predefined search terms was conducted to summarise the accumulated knowledge. Data was analysed by coding and categorising, then synthesized through development of themes. RESULTS: Eighteen of 116 studies met inclusion criteria. Promotional campaigns had varying impact on screening uptake for bowel cancer. Mass media was found to moderately increase screening, predominately amongst "worried well". Small media used in conjunction with other promotional activities, thus its effect on screening behaviours was unclear. One-on-one education was less effective and less feasible than group education in increasing intention to screen. Financial support was ineffective in increasing screening rates when compared to other promotional activities. Screening engagement increased because of special events and celebrity endorsement. CONCLUSION: Non-clinical promotional campaigns did impact uptake of bowel cancer screening engagement. However, little is evident on the effect of single types of promotion and most research is based on clinician directed campaigns. PRACTICE IMPLICATIONS: Cancer awareness and screening promotions should be implemented at community and clinical level to maximize effectiveness. Such an approach will ensure promotional activities are targeting consumers, thus strengthening screening engagement. PMID- 27270184 TI - Design of Hydrogen Storage Alloys/Nanoporous Metals Hybrid Electrodes for Nickel Metal Hydride Batteries. AB - Nickel metal hydride (Ni-MH) batteries have demonstrated key technology advantages for applications in new-energy vehicles, which play an important role in reducing greenhouse gas emissions and the world's dependence on fossil fuels. However, the poor high-rate dischargeability of the negative electrode materials hydrogen storage alloys (HSAs) limits applications of Ni-MH batteries in high power fields due to large polarization. Here we design a hybrid electrode by integrating HSAs with a current collector of three-dimensional bicontinuous nanoporous Ni. The electrode shows enhanced high-rate dischargeability with the capacity retention rate reaching 44.6% at a discharge current density of 3000 mA g(-1), which is 2.4 times that of bare HSAs (18.8%). Such a unique hybrid architecture not only enhances charge transfer between nanoporous Ni and HSAs, but also facilitates rapid diffusion of hydrogen atoms in HSAs. The developed HSAs/nanoporous metals hybrid structures exhibit great potential to be candidates as electrodes in high-performance Ni-MH batteries towards applications in new energy vehicles. PMID- 27270185 TI - Cannabis use and blood pressure levels: United States National Health and Nutrition Examination Survey, 2005-2012. AB - OBJECTIVE: Preclinical studies have reported acute cardiovascular effects of cannabis, including a dose-dependent increase in blood pressure (BP), whereas orthostatic hypotension may follow as a result of decreased vascular resistance. In case reports, evidence links cannabis with acute cardiovascular events in young and middle-aged adults. Here, we offer epidemiologic estimates on cannabis use and BP levels association from the US National Health and Nutrition Examination Surveys 2005-2012 (n = 12 426). METHODS: Computer-assisted self interviews assessed cannabis use. BP was determined by an average of up to four measurements taken during a single examination. Regression modeling was used to examine cannabis use and BP association. RESULTS: Recently active cannabis use was associated with increase in SBP (beta = 1.6; 95% confidence interval: 0.6, 2.7) in the age-sex-adjusted model. Additional covariate adjustment did not affect the positive association. No association between cannabis use and DBP was detected. CONCLUSION: A modest association between recent cannabis use and SBP was detected among a relatively large nationally representative sample of US adults. With the legalization of cannabis, there is a need for preclinical, clinical and prospective population-based research on the cardiovascular effects of cannabis use. PMID- 27270186 TI - Why in 2016 are patients with hypertension not 100% controlled? A call to action. AB - The objective is to consider the problem of high blood pressure (BP), a leading global risk factor, associated with substantial morbidity and mortality. Despite the availability of treatment guidelines and a wide range of therapies, BP control is suboptimal in many countries. Recent data indicate that only around 40% of patients manage to achieve an adequate level of BP control. A group of international experts in the field of hypertension met in 2008 to consider this problem. The resulting white paper delivered an urgent call to action and identified six key issues for improving BP control. In 2015, a working group of investigators spontaneously undertook an action with the primary aim of considering the current hypertension management situation in Europe, to discuss whether the situation had changed since 2008 and to determine what can be learnt from the projects in other continents, such as the Canadian Hypertension Education Program, which has shown that higher levels of BP control can be achieved across a general population. The working group identified the main challenges affecting the improvement of BP control today and suggests five key actions: identify the BP treatment target of less than 140/90 mmHg for the majority of patients, simplify treatment strategies and encourage pill reduction, decrease therapeutic inertia, improve patient empowerment, and involve healthcare systems and reduce the prevailing focus on drug costs in many healthcare systems. Implementing key actions identified by the working group may help to improve achievement of better BP control across Europe. PMID- 27270187 TI - Alpha-1 antitrypsin deficiency: a novel cause of isolated systolic resistant hypertension? PMID- 27270188 TI - Management of hypertension and diabetes mellitus by cardiovascular and endocrine physicians: a China registry. AB - OBJECTIVE: We investigated hypertension and diabetes mellitus in two management settings, namely cardiology and endocrinology, and their associations with albuminuria while accounting for the management of these two diseases. METHODS: Our multicentre registry included patients (>=20 years) seen for hypertension in cardiology or for diabetes mellitus in endocrinology. We administered a questionnaire and measured blood pressure, glycosylated haemoglobin A1c and albuminuria. RESULTS: Presence of both hypertension and diabetes was observed in 32.9% of hypertensive patients in cardiology (n = 1291) and 58.9% of diabetic patients in endocrinology (n = 1168). When both diseases were present, the use of combination antihypertensive therapy [odds ratio (OR) 0.31, P < 0.0001] and inhibitors of the renin-angiotensin system (OR 0.66, P = 0.0009) was less frequent in endocrinology than cardiology, and the use of combination antidiabetic therapy (OR 0.16, P < 0.0001) was less frequent in cardiology than endocrinology. The control of hypertension and diabetes, however, was not different between the two management settings (P >= 0.21), regardless of the therapeutic target (SBP/DBP < 140/90 or 130/80 mmHg and glycosylated haemoglobin A1c <7.0 or 6.5%). The prevalence of albuminuria was higher (P <= 0.02) in the presence of both diseases (23.3%) than those with either hypertension (12.6%) or diabetes alone (15.9%). CONCLUSION: Hypertension and diabetes mellitus were often jointly present, especially in the setting of endocrinology. The management was insufficient on the use of combination antihypertensive therapy and inhibitors of the renin-angiotensin system in endocrinology and for combination antidiabetic therapy in cardiology, indicating a need for more intensive management and better control of both clinical conditions. PMID- 27270189 TI - Strategies to meet the need for long-term data. AB - Chronic diseases afflict patients for many years, often to the end of life, and there is increasing need for estimating lifelong risk and for evaluating the effects of treatment in the long term. Yet recommendations for lifelong treatment are most frequently based on findings from randomized clinical trials lasting only a few years. There is therefore a clear need for much longer term data, and here we present the advantages and disadvantages of many strategies, including the use of long-term posttrial follow-up, of long-term prospective cohort studies, registry databases, and of administrative databases. We also emphasize the need for long-term cost-effectiveness studies. One of the most promising strategies comes from linkage of data gathered through the ever-expanding pool of administrative databases worldwide with data from other sources, including randomized trials and the many forms of observational study. PMID- 27270190 TI - Prevalence of Anaplasma phagocytophilum in small rodents in France. AB - Anaplasma phagocytophilum is an emerging zoonotic tick-borne pathogen affecting a wide range of mammals. Rodents are suspected to be natural reservoirs for this bacterium, but their role in the epidemiologic cycles affecting domestic animals and wild ungulates has not been demonstrated. This study aimed to improve our knowledge on A. phagocytophilum prevalence in Apodemus sylvaticus, A. flavicollis and Myodes glareolus using data collected in 2010 in one area in eastern France and in 2012-2013 in two others areas in western France. Rodents were captured in each site and infection was tested using qualitative real-time PCR assays on either blood or spleen samples. Prevalence showed high variability among sites. The highest prevalence was observed in the most eastern site (with an average infection rate of 22.8% across all species), whereas no rodent was found to be PCR positive in the south-west site and only 6.6% were positive in the north-west of France. Finally, a significant increase in prevalence was observed in autumn samples compared to spring samples in the north-west, but no change was found in the other two sites. PMID- 27270191 TI - [Trauma-focused Cognitive-behavioral Therapy with children and adolescents: Practice, evidence base, and future directions]. AB - Trauma-focused cognitive behavioral therapy (Tf-CBT) is an evidence-based trauma therapy for children and adolescents aged 3-17 years with posttraumatic stress disorder (PTSD). One supportive caregiver is regularly included in the therapeutic process. Tf-CBT consists of eight components and can be summarized by the acronym P.R.A.C.T.I.C.E: Psychoeducation and Parenting skills, Relaxation skills, Affective modulation skills, Cognitive coping skills, Trauma narrative and cognitive processing of the traumatic event(s), In vivo mastery of trauma reminders, Conjoint child-parent sessions, and Enhancing safety and future developmental trajectory. Based on a total of 13 randomized controlled trials, several meta-analyses and systematic reviews confirm the efficacy of Tf-CBT, which received evidence level Ia in several international guidelines and is therefore recommended as first-line treatment for children and adolescents with PTSD. PMID- 27270193 TI - Combatting loneliness in the community. PMID- 27270194 TI - Management of eczema and psoriasis in the community. PMID- 27270192 TI - Trust, but verify. The errors and misinterpretations in the Cochrane analysis by O. J. Storebo and colleagues on the efficacy and safety of methylphenidate for the treatment of children and adolescents with ADHD. AB - Objective: A recent Cochrane review published by O. J. Storebo and colleagues (2015) raised substantial doubts about the benefit from stimulant medication with methylphenidate in the treatment of childhood ADHD due to the overall poor quality of studies. The systematic review thus contradicts all previous reviews and meta-analyses. Method: We here detail various examples of errors, inconsistencies, and misinterpretations in the review which led to false results and inadequate conclusions. Results: We demonstrate that the study selection is flawed and undertaken without sufficient scientific justification resulting in an underestimation of effect sizes, which, furthermore, are inadmissibly clinically interpreted. The methodology of the assessment of bias and quality is not objective and cannot be substantiated by the data. Conclusions: Cochrane reviews lay claim to a high scientific quality and substantial relevance for evidence based clinical decisions. The systematic review by Storebo and colleagues (2015) illustrates that, despite adhering to strict standards and high-quality protocols, even Cochrane works should be critically read and verified, sometimes with surprising results. PMID- 27270195 TI - Making maintaining dignity a top priority: caring for older people with a stoma in the community. PMID- 27270196 TI - Improving quality of care and reducing unnecessary hospital admissions: a literature review. AB - As the UK population lives to older ages, with more complex health and social care needs, there comes a time when going to live in a care home might be essential for a frail, older person. Residents and their families expect high quality care in return for the costs of their placements, but often find this is not the case ( Help the Aged, 2006 ). In order to improve quality in care homes, the Lincolnshire Community Health Services NHS Trust are piloting a care home support team. The new service aims to provide education and training to an unpredictable workforce, with the addition of regular ward rounds in care homes to ensure more proactive care for residents, in order to reduce unnecessary hospital admissions and improve the quality of care offered. This article looks at the literature relating to education and training for staff in care homes to support this service. It also aims to use the reviewed articles to identify specific training and education needed to improve quality of care for residents and reduce avoidable hospital admissions. PMID- 27270197 TI - The role of the intermediate care team in detecting and responding to loneliness in older clients. AB - The intermediate care team supports patients in their own homes to manage complex needs. They are ideally placed in the community to identify older adults at risk of loneliness. However, little is known about how intermediate care team professionals perceive, detect or respond to loneliness in their clients. This study explores intermediate care team professionals' attitudes to loneliness in the context of perceived service priorities and their experiences of managing loneliness in their clients. Eight professionals (n=2 physiotherapists, n=3 occupational therapists, n=3 nurses) took part in semi-structured interviews. Data were analysed thematically using framework analysis, applying the theory of planned behaviour as an interpretive framework. Intermediate care team professionals see loneliness as a significant issue for many of their older clients but a low priority for intermediate care team services. They believe that loneliness often goes undetected because it is difficult to measure objectively. Barriers to managing loneliness included high workloads, unsatisfactory referral systems and lack of close working with social care and independent sector services. Brief but reliable loneliness assessments into routine practice, receiving training on detecting and managing loneliness, and improving working relationships with social care and independent sector services were highlighted as strategies that could improve the detection and management of loneliness in intermediate care team clients. PMID- 27270198 TI - In whose best interests? A case study of a family affected by dementia. AB - Many people with dementia are cared for by family members. Family carers often feel bound to support the person with dementia at the expense of their own needs, which can be neglected. They often experience distress when making decisions, especially over ethical dilemmas when their own interests and those of the person being cared for conflict. This paper presents a case study approach to consider best interests decision making for families affected by dementia. In the case study, a carer is supporting his father to remain living at home although he feels this unsafe and the demands of this cause tension with his family and affect his performance at work. PMID- 27270199 TI - Considering the benefits of egg consumption for older people at risk of sarcopenia. AB - Sarcopenia is an important health issue for older people. It is closely linked with frailty and malnutrition and can significantly reduce both health and quality of life for those affected. Sarcopenic decline in muscle mass can start as early as the fourth and fifth decade of life, so the maintenance of muscle mass throughout adulthood, through regular physical activity and a balanced diet, should be an important consideration in reducing the risk of sarcopenia in older age. Maintaining regular exercise throughout older age remains key to the treatment of sarcopenia, as does an adequate intake of nutrients, including high quality protein and vitamin D. A significant proportion of older people fail to meet the recommended requirements for protein; it has also been suggested that the requirements in existing recommendations could be higher. Evidence is emerging that an adequate intake of protein at each meal may be required to optimise muscle synthesis in older people. Eggs are an inexpensive, widely available and easily digestible source of high-quality protein and contain a significant proportion of leucine, an amino acid that is important for muscle synthesis, as well as many other nutrients of significance for older people, including vitamin D and omega-3 fatty acids. For many older people, eggs are a familiar and acceptable protein food at breakfast and other meals. Encouraging both those approaching older age and older people to include eggs more frequently, as part of a healthy, balanced diet and in addition to physical activity, could help them maintain their muscle strength and function, thereby preserving their functional capacity and reducing morbidity, mortality and healthcare costs associated with sarcopenia. PMID- 27270200 TI - The changing nature of the district nurse patient relationship. AB - In this article Richard Griffith considers three recent developments in policy and law that have changed the nature of the relationship between district nurses and their patients. The traditional, often paternalistic, professional knows best approach must now give way to a patient focused partnership. PMID- 27270201 TI - A look at assessing Achilles tendinopathy in the community. PMID- 27270202 TI - Achieving quality of life against all the odds. PMID- 27270203 TI - Identifying hearing loss in older people. PMID- 27270204 TI - Academic careers: what do early career researchers think? PMID- 27270205 TI - Quantitative Determination of Four Azo Dyes in Rat Plasma with Solid-Phase Extraction and UFLC-MS-MS Analysis: Application to a Pharmacokinetic Study. AB - A rapid and sensitive ultra-fast liquid chromatography tandem mass spectrometry method, followed by simple protein precipitation and solid-phase extraction, has been developed and validated for the quantitative determination of four azo dyes (Para red, Solvent yellow 2, Solvent red 1 and Sudan red 7B) in rat plasma using D5-Sudan I as the internal standard. The optimal separation was accomplished on an Agilent Eclipse Plus C18 column (100 * 2.1 mm, 1.8 MUm) with gradient elution using the mobile phase including acetonitrile and water (containing 0.1% formic acid). The flow rate was 0.45 mL/min. The detection was conducted by means of electrospray ionization mass spectrometry in positive ion mode with multiple reaction monitoring. The calibration curves showed good linearity, with correlation coefficients >0.998 for all of the analytes within the concentration range. The lower limits of quantification (LLOQs) of Para red, Solvent yellow 2, Solvent red 1 and Sudan red 7B in rat plasma were 1.0, 0.1, 0.1 and 0.1 MUg/L, respectively. The intra- and interday relative standard deviations were <=9.6 and <=12.4%, respectively, and the accuracy was in the range of -5.8 to -9.5%. The average recoveries were between 81.49 and 118.65%, and the matrix effects were satisfactory in the biological matrices. The fully validated method has been successfully applied in measuring levels of the four azo dyes in rat plasma following oral administration of 20.0 mg/kg of analytes in rats, which was suitable for the pharmacokinetic studies of the azo dyes. PMID- 27270206 TI - Dissolved oxygen content prediction in crab culture using a hybrid intelligent method. AB - A precise predictive model is needed to obtain a clear understanding of the changing dissolved oxygen content in outdoor crab ponds, to assess how to reduce risk and to optimize water quality management. The uncertainties in the data from multiple sensors are a significant factor when building a dissolved oxygen content prediction model. To increase prediction accuracy, a new hybrid dissolved oxygen content forecasting model based on the radial basis function neural networks (RBFNN) data fusion method and a least squares support vector machine (LSSVM) with an optimal improved particle swarm optimization(IPSO) is developed. In the modelling process, the RBFNN data fusion method is used to improve information accuracy and provide more trustworthy training samples for the IPSO LSSVM prediction model. The LSSVM is a powerful tool for achieving nonlinear dissolved oxygen content forecasting. In addition, an improved particle swarm optimization algorithm is developed to determine the optimal parameters for the LSSVM with high accuracy and generalizability. In this study, the comparison of the prediction results of different traditional models validates the effectiveness and accuracy of the proposed hybrid RBFNN-IPSO-LSSVM model for dissolved oxygen content prediction in outdoor crab ponds. PMID- 27270207 TI - Automated finite element modeling of the lumbar spine: Using a statistical shape model to generate a virtual population of models. AB - Population-based modeling of the lumbar spine has the potential to be a powerful clinical tool. However, developing a fully parameterized model of the lumbar spine with accurate geometry has remained a challenge. The current study used automated methods for landmark identification to create a statistical shape model of the lumbar spine. The shape model was evaluated using compactness, generalization ability, and specificity. The primary shape modes were analyzed visually, quantitatively, and biomechanically. The biomechanical analysis was performed by using the statistical shape model with an automated method for finite element model generation to create a fully parameterized finite element model of the lumbar spine. Functional finite element models of the mean shape and the extreme shapes (+/-3 standard deviations) of all 17 shape modes were created demonstrating the robust nature of the methods. This study represents an advancement in finite element modeling of the lumbar spine and will allow population-based modeling in the future. PMID- 27270208 TI - Efavirenz and ritonavir-boosted lopinavir use exhibited elevated markers of atherosclerosis across age groups in people living with HIV in Ethiopia. AB - BACKGROUND: HIV patients on highly-active antiretroviral therapy (HAART) have shown elevated incidence of dyslipidemia, lipodystrophy, and markers of cardiovascular disease. Evidence is beginning to emerge that implicates efavirenz (EFV) as a potential mediator of early on-set cardiovascular disease. METHODS: Pediatric and adult HIV-infected HAART-naive, EFV-treated, nevirapine (NVP) treated, and ritonavir-boosted lopinavir (LPV/r)-treated subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Pulse wave velocity (PWV), carotid intima-media thickness (cIMT), carotid arterial stiffness, brachial artery flow-mediated dilation (FMD), body mass index, waist-to-hip circumference ratio, and skinfold thickness were measured. CD4+ cell count, fasting glucose, lipoprotein profiles and triglycerides were also determined. Results were segmented into pediatric (6-17 years of age), young adults (25-39 years old) and older adults (40-60 years old). RESULTS: PWV was generally elevated in EFV- and LPV/r-treated subjects compared to NVP-treated subjects across age groups. cIMT was elevated in EFV- and LPV/r-treated compared to NVP-treated older adults and in EFV-treated compared to HAART-naive older adults. FMD was impaired in EFV- and LPV/r-treated compared to HAART-naive younger adults, in EFV-treated compared to NVP-treated young and older adults, and in LPV/r-treated compared to NVP-treated older adults. Differences in lipoprotein profiles and skinfold thickness with HAART regimen were observed in pediatric and young adults, but less so in older adults. CONCLUSIONS: Whereas LPV/r and other protease inhibitors have long been recognized as mediators of HIV/HAART-associated atherosclerosis, this report supports the emerging evidence that EFV may also mediate cardiovascular disease in people living with HIV on HAART. PMID- 27270211 TI - Harnessing mesenchymal stem cell homing as an anticancer therapy. AB - INTRODUCTION: Mesenchymal stromal cells (MSCs) are non-hematopoietic progenitor cells that have been exploited as vehicles for cell-based cancer therapy. The general approach is based on the innate potential of adoptively applied MSC to undergo facilitated recruitment to malignant tissue. MSC from different tissue sources have been engineered using a variety of therapy genes that have shown efficacy in solid tumor models. AREAS COVERED: In this review we will focus on the current developments of MSC-based gene therapy, in particular the diverse approaches that have been used for MSCs-targeted tumor therapy. We also discuss some outstanding issues and general prospects for their clinical application. EXPERT OPINION: The use of modified mesenchymal stem cells as therapy vehicles for the treatment of solid tumors has progressed to the first generation of clinical trials, but the general field is still in its infancy. There are many questions that need to be addressed if this very complex therapy approach is widely applied in clinical settings. More must be understood about the mechanisms underlying tumor tropism and we need to identify the optimal source of the cells used. Outstanding issues also include the therapy transgenes used, and which tumor types represent viable targets for this therapy. PMID- 27270209 TI - Modulation of oxidative stress and subsequent induction of apoptosis and endoplasmic reticulum stress allows citral to decrease cancer cell proliferation. AB - The monoterpenoid, citral, when delivered through PEG-b-PCL nanoparticles inhibits in vivo growth of 4T1 breast tumors. Here, we show that citral inhibits proliferation of multiple human cancer cell lines. In p53 expressing ECC-1 and OVCAR-3 but not in p53-deficient SKOV-3 cells, citral induces G1/S cell cycle arrest and apoptosis as determined by Annexin V staining and increased cleaved caspase3 and Bax and decreased Bcl-2. In SKOV-3 cells, citral induces the ER stress markers CHOP, GADD45, EDEM, ATF4, Hsp90, ATG5, and phospho-eIF2alpha. The molecular chaperone 4-phenylbutyric acid attenuates citral activity in SKOV-3 but not in ECC-1 and OVCAR-3 cells. In p53-expressing cells, citral increases phosphorylation of serine-15 of p53. Activation of p53 increases Bax, PUMA, and NOXA expression. Inhibition of p53 by pifithrin-alpha, attenuates citral-mediated apoptosis. Citral increases intracellular oxygen radicals and this leads to activation of p53. Inhibition of glutathione synthesis by L-buthionine sulfoxamine increases potency of citral. Pretreatment with N-acetylcysteine decreases phosphorylation of p53 in citral-treated ECC-1 and OVCAR-3. These results define a p53-dependent, and in the absence of p53, ER stress-dependent mode of action of citral. This study indicates that citral in PEG-b-PCL nanoparticle formulation should be considered for treatment of breast and other tumors. PMID- 27270210 TI - Evaluation of the ability of three physical activity monitors to predict weight change and estimate energy expenditure. AB - Activity monitors such as the Actical accelerometer, the Sensewear armband, and the Intelligent Device for Energy Expenditure and Activity (IDEEA) are commonly validated against gold standards (e.g., doubly labeled water, or DLW) to determine whether they accurately measure total daily energy expenditure (TEE) or activity energy expenditure (AEE). However, little research has assessed whether these parameters or others (e.g., posture allocation) predict body weight change over time. The aims of this study were to (i) test whether estimated energy expenditure or posture allocation from the devices was associated with weight change during and following a low-calorie diet (LCD) and (ii) compare free-living TEE and AEE predictions from the devices against DLW before weight change. Eighty seven participants from 2 clinical trials wore 2 of the 3 devices simultaneously for 1 week of a 2-week DLW period. Participants then completed an 8-week LCD and were weighed at the start and end of the LCD and 6 and 12 months after the LCD. More time spent walking at baseline, measured by the IDEEA, significantly predicted greater weight loss during the 8-week LCD. Measures of posture allocation demonstrated medium effect sizes in their relationships with weight change. Bland-Altman analyses indicated that the Sensewear and the IDEEA accurately estimated TEE, and the IDEEA accurately measured AEE. The results suggest that the ability of energy expenditure and posture allocation to predict weight change is limited, and the accuracy of TEE and AEE measurements varies across activity monitoring devices, with multi-sensor monitors demonstrating stronger validity. PMID- 27270212 TI - Intracellularly survived Staphylococcus aureus after phagocytosis are more virulent in inducing cytotoxicity in fresh murine peritoneal macrophages utilizing TLR-2 as a possible target. AB - Staphylococcus aureus with high virulence potential is contributing to a current public health crisis in both hospital and community settings. TLR-2 and generation of reactive oxygen species (ROS) by phagocytic cells is thought to be an important component of the host's immunity against S. aureus infection. However, response of S. aureus against modulation of host-derived ROS in absence of TLR-2 during acute staphylococcal infection is still remains unclear. Peritoneal macrophages were pretreated with either inhibitors of superoxide dismutase (SOD) or catalase in presence or absence of anti TLR-2 antibody and were infected with S. aureus strain AG-789. Bacteria were recovered after time dependent phagocytosis; intracellular killing, level and expression of SOD and catalase were measured. Phagocytosed bacteria from respective groups were further used for infection to fresh peritoneal macrophages as well as for in vivo infection. Levels of ROS, cytokine, lysozyme, antioxidant enzymes activity and TLR-2 expression were measured. Results revealed that more bacteria were escaped killing in SOD and catalase inhibitor pretreated TLR-2 neutralized macrophages, found to express more catalase and are antibiotic resistant. Infection of fresh macrophages with S. aureus, recovered from SOD and catalase inhibited TLR-2 neutralized macrophages induced lower ROS, lysozyme and cytokine production and caused increased bacterial count. Furthermore, bacterial antioxidants by modulating host-derived ROS could regulate the cell surface TLR-2 expression in murine peritoneal macrophages. So, in the early phase of infection, TLR-2 participates in the innate immune response and targeting bacterial antioxidants might be useful in the alleviation of Staphylococcus aureus infection. PMID- 27270213 TI - Single-Molecule Patch-Clamp FRET Anisotropy Microscopy Studies of NMDA Receptor Ion Channel Activation and Deactivation under Agonist Ligand Binding in Living Cells. AB - N-methyl-d-aspartate (NMDA) receptor ion channel is activated by the binding of two pairs of glycine and glutamate along with the application of action potential. Binding and unbinding of ligands changes its conformation that plays a critical role in the open-close activities of NMDA receptor. Conformation states and their dynamics due to ligand binding are extremely difficult to characterize either by conventional ensemble experiments or single-channel electrophysiology method. Here we report the development of a new correlated technical approach, single-molecule patch-clamp FRET anisotropy imaging and demonstrate by probing the dynamics of NMDA receptor ion channel and kinetics of glycine binding with its ligand binding domain. Experimentally determined kinetics of ligand binding with receptor is further verified by computational modeling. Single-channel patch clamp and four-channel fluorescence measurement are recorded simultaneously to get correlation among electrical on and off states, optically determined conformational open and closed states by FRET, and binding-unbinding states of the glycine ligand by anisotropy measurement at the ligand binding domain of GluN1 subunit. This method has the ability to detect the intermediate states in addition to electrical on and off states. Based on our experimental results, we have proposed that NMDA receptor gating goes through at least one electrically intermediate off state, a desensitized state, when ligands remain bound at the ligand binding domain with the conformation similar to the fully open state. PMID- 27270214 TI - Sympathetic innervation of the kidney in health and disease: Emphasis on the role of purinergic cotransmission. AB - There is introductory information about non-synaptic transmission at sympathetic neuroeffector junctions and sympathetic nerve cotransmission utilizing noradrenaline and ATP as cotransmitters. Then the organzation and location of sympathetic nerves in different sites in the kidney are described, including renal arteries, juxtaglomerular arterioles and renal tubules. Sympathetic nervous control of glomerular filtration rate and of renin secretion are discussed. Evidence, obtained largely from experiments on animals, for sympathetic nerve modulation of the transport of water, sodium and other ions in the collecting duct of the nephron is described. Finally, there is coverage of the roles of sympathetic nerves in renal diseases, including hypertension, diabetes, hypothyroidism and ischaemia. PMID- 27270215 TI - Distinct Global Brain Dynamics and Spatiotemporal Organization of the Salience Network. AB - One of the most fundamental features of the human brain is its ability to detect and attend to salient goal-relevant events in a flexible manner. The salience network (SN), anchored in the anterior insula and the dorsal anterior cingulate cortex, plays a crucial role in this process through rapid detection of goal relevant events and facilitation of access to appropriate cognitive resources. Here, we leverage the subsecond resolution of large multisession fMRI datasets from the Human Connectome Project and apply novel graph-theoretical techniques to investigate the dynamic spatiotemporal organization of the SN. We show that the large-scale brain dynamics of the SN are characterized by several distinctive and robust properties. First, the SN demonstrated the highest levels of flexibility in time-varying connectivity with other brain networks, including the frontoparietal network (FPN), the cingulate-opercular network (CON), and the ventral and dorsal attention networks (VAN and DAN). Second, dynamic functional interactions of the SN were among the most spatially varied in the brain. Third, SN nodes maintained a consistently high level of network centrality over time, indicating that this network is a hub for facilitating flexible cross-network interactions. Fourth, time-varying connectivity profiles of the SN were distinct from all other prefrontal control systems. Fifth, temporal flexibility of the SN uniquely predicted individual differences in cognitive flexibility. Importantly, each of these results was also observed in a second retest dataset, demonstrating the robustness of our findings. Our study provides fundamental new insights into the distinct dynamic functional architecture of the SN and demonstrates how this network is uniquely positioned to facilitate interactions with multiple functional systems and thereby support a wide range of cognitive processes in the human brain. PMID- 27270216 TI - Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation. AB - Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury, and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis. Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1beta, transforming growth factor-beta (TGF-beta), drosophila mothers against DPP homolog (Smad) 2/3 phosphorylation and Smad4 were increased in animal and H9c2 cell models. These pathological processes were further evaluated in ox LDL or fructose-exposed H9c2 cells pretreated with ROS scavenger and CD36 specific inhibitor, or IRAK1/4 inhibitor, and transfected with CD36, NLRP3, or IRAK4/1 siRNA, demonstrating that NLPR3 inflammasome activation through CD36 mediated TLR4/6-IRAK4/1 signaling may promote cardiac inflammation and fibrosis. Cinnamaldehyde and allopurinol reduced cardiac oxidative stress to suppress NLPR3 inflammasome activation and TGF-beta/Smads signaling by inhibiting CD36-mediated TLR4/6-IRAK4/1 signaling under fructose induction. These results suggest that the blockage of CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation by cinnamaldehyde and allopurinol may protect against fructose-induced cardiac inflammation and fibrosis. PMID- 27270217 TI - Inter-pregnancy Weight Change and Risks of Severe Birth-Asphyxia-Related Outcomes in Singleton Infants Born at Term: A Nationwide Swedish Cohort Study. AB - BACKGROUND: Maternal overweight and obesity are associated with increased risks of birth-asphyxia-related outcomes, but the mechanisms are unclear. If a change of exposure (i.e., maternal body mass index [BMI]) over time influences risks, this would be consistent with a causal relationship between maternal BMI and offspring risks. Our objective was to investigate associations between changes in maternal BMI between consecutive pregnancies and risks of birth-asphyxia-related outcomes in the second offspring born at term. METHODS AND FINDINGS: This study was a prospective population-based cohort study that included 526,435 second-born term (>=37 wk) infants of mothers with two consecutive live singleton term births in Sweden between January 1992 and December 2012. We estimated associations between the difference in maternal BMI between the first and second pregnancy and risks of low Apgar score (0-6) at 5 min, neonatal seizures, and meconium aspiration in the second-born offspring. Odds ratios (ORs) were adjusted for BMI at first pregnancy, maternal height, maternal age at second delivery, smoking, education, mother's country of birth, inter-pregnancy interval, and year of second delivery. Analyses were also stratified by BMI (<25 versus >=25 kg/m2) in the first pregnancy. Risks of low Apgar score, neonatal seizures, and meconium aspiration increased with inter-pregnancy weight gain. Compared with offspring of mothers with stable weight (BMI change of -1 to <1 kg/m2), the adjusted OR for a low Apgar score in the offspring of mothers with a BMI change of 4 kg/m2 or more was 1.33 (95% CI 1.12-1.58). The corresponding risks for neonatal seizures and meconium aspiration were 1.42 (95% CI 1.00-2.02) and 1.78 (95% CI 1.19-2.68), respectively. The increased risk of neonatal seizures related to weight gain appeared to be restricted to mothers with BMI < 25 kg/m2 in the first pregnancy. A study limitation was the lack of data on the effects of obstetric interventions and neonatal resuscitation efforts. CONCLUSIONS: Risks of birth-asphyxia-related outcomes increased with maternal weight gain between pregnancies. Preventing weight gain before and in between pregnancies may improve neonatal health. PMID- 27270218 TI - The impact of new-onset cancer among veterans who are receiving warfarin for atrial fibrillation and venous thromboembolism. AB - BACKGROUND: A new cancer diagnosis adds significant complexity and uncertainty to the management of pre-existing warfarin therapy. OBJECTIVES: To determine how new onset cancer affects anticoagulation control and outcomes among patients who had been receiving warfarin for atrial fibrillation (AF) compared to patients who had been receiving warfarin for venous thromboembolism (VTE) prior to cancer diagnosis. PATIENTS/METHODS: This cohort study started with 122,875 veterans who had been receiving warfarin for at least six months from a VA Medical Center between 10/1/06 and 9/30/08. We identified patients with incident cancer during this interval, and excluded those with a prior cancer history. We analyzed percent time in therapeutic range (TTR) at 6 and 12-month intervals after cancer diagnosis compared to pre-cancer baseline, as well as crude rates of warfarin relevant outcomes (stroke, major bleeding, mortality) between patients with AF and VTE. RESULTS: Among patients with new-onset cancer, patients anticoagulated for AF outnumbered those anticoagulated for VTE more than 2.5-fold. There were no significant differences in TTR by indication for warfarin in months 0-6 or 7-12 following cancer diagnosis, but TTR decreased significantly compared to the pre cancer baseline for both groups in months 0-6. As expected, cancer patients with VTE had significantly worse mortality at six months and one year compared to cancer patients with AF. CONCLUSION: Patients receiving chronic warfarin therapy who are newly diagnosed with cancer experience a significant decrease in TTR in the first 6months after diagnosis, regardless of indication for anticoagulation. This effect appears to attenuate in months 7-12. PMID- 27270219 TI - Age at cancer diagnosis, non-O blood group and asparaginase therapy are independently associated with deep venous thrombosis in pediatric oncology patients: A risk model. AB - INTRODUCTION: Pediatric oncology patients are at increased risk for deep venous thrombosis (DVT). Determining the sub-population of children at increased DVT risk is critical for optimum clinical management. Therefore, the aim of the current study was to identify clinical risk factors for DVT which are easily identifiable at cancer diagnosis. MATERIALS AND METHODS: A Canadian multicenter case control study in survivors of childhood cancer. Survivors who had DVT (Cases) while being treated for pediatric cancer where matched by center with a minimum of two survivors who did not experience DVT (Controls). Clinical information including age at diagnosis, type of cancer and chemotherapy were collected. Genotyping of blood group was done by single nucleotide polymorphisms analysis. RESULTS: 218 subjects were recruited at 4 Canadian pediatric centers. Multivariable analysis demonstrated 3 significant variables (reported as Odds Ratio (OR), (95% CI), p value): age at diagnosis p<0.001, non-O blood group OR 2.6 (1.3-5.2) p=0.005 and asparaginase treatment OR 2.4 (1.2-4.8) p=0.011. In order to optimise clinical utility, we reanalysed the study data with age at diagnosis categorised into four subgroups 0-<=2years, >2-<=7years, >7<=10years, >10years. A significant association with DVT were seen in children 0-<=2years (OR 3.1 (1.1-8.3) p=0.026) and >10years (OR 3.8, 1.7-8.5 p=0.001). Significant associations with DVT remained for non-O blood group, OR 2.2 (1.2-4.4) p=0.016 and asparaginase treatment, OR 2.1 (1.1-4.0) p=0.027. The value for the clinical risk model receiver operating characteristics curve was 0.67. CONCLUSIONS: We have shown 3 independent risk factors for DVT in childhood cancer. PMID- 27270220 TI - Effects of mineralocorticoid receptor antagonists on the risk of thrombosis, bleeding and mortality: A systematic review and meta-analysis of randomized controlled trials. PMID- 27270221 TI - (+/-)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum. AB - Two pairs of new enantiomers with unusual 5,5-spiroketal cores, termed (+/-) japonones A and B [(+/-)-1 and (+/-)-2], were obtained from Hypericum japonicum Thunb. The absolute configurations of (+/-)-1 and (+/-)-2 were characterized by extensive analyses of spectroscopic data and calculated electronic circular dichroism (ECD) spectra, the application of modified Mosher's methods, and the assistance of quantum chemical predictions (QCP) of (13)C NMR chemical shifts. Among these metabolites, (+)-1 exhibited some inhibitory activity on Kaposi's sarcoma associated herpesvirus (KSHV). Virtual screening of (+/-)-1 and (+/-)-2 were conducted using the Surflex-Dock module in the Sybyl software, and (+)-1 exhibited ability to bind with ERK to form key interactions with residues Lys52, Pro56, Ile101, Asp165, Gly167 and Val99. PMID- 27270222 TI - An Analysis of Costs and Health Co-Benefits for a U.S. Power Plant Carbon Standard. AB - Reducing carbon dioxide (CO2) emissions from power plants can have important "co benefits" for public health by reducing emissions of air pollutants. Here, we examine the costs and health co-benefits, in monetary terms, for a policy that resembles the U.S. Environmental Protection Agency's Clean Power Plan. We then examine the spatial distribution of the co-benefits and costs, and the implications of a range of cost assumptions in the implementation year of 2020. Nationwide, the total health co-benefits were $29 billion 2010 USD (95% CI: $2.3 to $68 billion), and net co-benefits under our central cost case were $12 billion (95% CI: -$15 billion to $51 billion). Net co-benefits for this case in the implementation year were positive in 10 of the 14 regions studied. The results for our central case suggest that all but one region should experience positive net benefits within 5 years after implementation. PMID- 27270223 TI - Differential effects of male nutrient balance on pre- and post-copulatory traits, and consequences for female reproduction in Drosophila melanogaster. AB - Male fitness depends on the expression of costly traits involved in obtaining mates (pre-copulatory) and fertilization (post-copulatory). However, very little is known about the nutrient requirements for these traits and whether males compromise their diet to maximize one trait at the expense of another. Here we used Nutritional Geometry to investigate macronutrient requirements for pre- and post-copulatory traits in Drosophila, when males were the first or second to mate with females. We found no significant effects of male diet on sperm competitiveness. However, although males self-regulate their macronutrient intake at a protein-to-carbohydrate ratio ("P:C ratio") of 1:1.5, this ratio does not coincide with their optima for several key reproductive traits: both the short term (~24 hr) rate of offspring production after a female's first mating, as well as the total offspring number sired when males were second to mate were maximized at a P:C ratio of 1:9, whereas male attractiveness (latency to mate), were maximised at a P:C ratio of 1:1. These results suggest a compromised optimum diet, and no single diet that simultaneously maximizes all male reproductive traits. The protein intake of first males also negatively affected female offspring production following remating, suggesting a long-term intersexual effect of male nutrition. PMID- 27270224 TI - Apoptosis-associated protein expression in human salivary gland morphogenesis. AB - OBJECTIVE: Salivary gland (SG) development is based on branching morphogenesis, in which programmed cell death has been proposed to play a role in cell signalling and organ shaping. In the mouse salivary gland apoptosis has been suggested to play a key role in lumen formation, removing the central cells of the epithelial stalks. Here we analyse the expression of several anti- and pro regulators of apoptosis during human SG development in a range of developmental stages. DESIGN: Foetal SGs obtained from the University of Sao Paulo were analysed by immunohistochemistry to assess the expression of apoptosis-associated proteins: caspases (caspase-6, -7, -9 and cleaved caspase-3), Bcl-2 family members (Bax, Bak, Bad, Bid, Bcl-2, Bcl-x and Bcl-xL), Survivin (BIRC5), Cytochrome C and Apaf-1. RESULTS: Nuclear expression of Bax and Bak was identified in presumptive luminal areas at initial stages, while Bcl-xL showed the most relevant anti-apoptotic activity. Caspase-6, -7 and -9 were expressed during all stages, while interestingly cleaved caspase-3 showed no prominent expression, indicating that caspase-7 is the main effector. Apoptosome complex components Apaf-1 and Cytochrome C, as well as survivin were all positive in developing glands. CONCLUSIONS: The particular expression pattern of several apoptotic regulators in human SG development suggests the existence of a fundamental role for apoptosis during duct formation. The absence of Bad and Bid expressions indicates that the instrinsic pathway is more active then the extrinsic during human gland formation. The subcellular localisation of intrinsic apoptosis proteins correlated with apoptotic activity, but also suggested additional non-apoptotic functions. PMID- 27270225 TI - Monocyte chemotactic protein-1, RANTES and macrophage migration inhibitory factor levels in gingival crevicular fluid of metabolic syndrome patients with gingivitis. AB - OBJECTIVE: The aim of the present study was to determine gingival crevicular fluid (GCF) levels of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted protein (RANTES) and macrophage migration inhibitory factor (MIF) in metabolic syndrome patients with gingivitis. DESIGN: Twenty metabolic syndrome patients with gingivitis (MSG), 20 MetS patients with clinically healthy periodontium (MSH), 20 systemically healthy subjects with gingivitis and 20 subjects who were both systemically and periodontally healthy were included. Periodontal and systemical parameters were recorded. GCF MCP-1, RANTES and MIF levels were assayed by enzyme-linked immunosorbent assay method. RESULTS: MSG and MSH groups had elevated blood pressure, triglyceride, waist circumference and fasting glucose values in comparison to gingivitis and healthy groups (P<0.0001). Clinical periodontal parameters were higher in MSG and gingivitis groups when compared to those of the MSH and healthy groups (P<0.0001). MCP-1 and RANTES levels (ng/mg total protein) of MSG group were higher than those of the MSH groups (P=0.005, P=0.0001, respectively). Also gingivitis group had higher MCP-1, RANTES and MIF levels compared to the healthy group (P=0.011, P=0.0001, P=0.011 respectively). The RANTES level of MSG group was significantly higher than those of the gingivitis group (P=0.01), but MCP-1 and MIF levels were similar in the MSG and gingivitis groups (P>0.05). CONCLUSION: Elevated levels of GCF RANTES in MetS patients with gingivitis might associate with the presence of increased gingival inflammation by MetS. Low-grade systemic inflammation associated with MetS and adipose tissue derived RANTES might lead to altered GCF RANTES levels in the presence of gingival inflammation. PMID- 27270226 TI - Hematocrit-Independent Quantitation of Stimulants in Dried Blood Spots: Pipet versus Microfluidic-Based Volumetric Sampling Coupled with Automated Flow-Through Desorption and Online Solid Phase Extraction-LC-MS/MS Bioanalysis. AB - A workflow overcoming microsample collection issues and hematocrit (HCT)-related bias would facilitate more widespread use of dried blood spots (DBS). This report describes comparative results between the use of a pipet and a microfluidic-based sampling device for the creation of volumetric DBS. Both approaches were successfully coupled to HCT-independent, fully automated sample preparation and online liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis allowing detection of five stimulants in finger prick blood. Reproducible, selective, accurate, and precise responses meeting generally accepted regulated bioanalysis guidelines were observed over the range of 5-1000 ng/mL whole blood. The applied heated flow-through solvent desorption of the entire spot and online solid phase extraction (SPE) procedure were unaffected by the blood's HCT value within the tested range of 28.0-61.5% HCT. Enhanced stability for mephedrone on DBS compared to liquid whole blood was observed. Finger prick blood samples were collected using both volumetric sampling approaches over a time course of 25 h after intake of a single oral dose of phentermine. A pharmacokinetic curve for the incurred phentermine was successfully produced using the described validated method. These results suggest that either volumetric sample collection method may be amenable to field-use followed by fully automated, HCT-independent DBS-SPE-LC-MS/MS bioanalysis for the quantitation of these representative controlled substances. Analytical data from DBS prepared with a pipet and microfluidic-based sampling devices were comparable, but the latter is easier to operate, making this approach more suitable for sample collection by unskilled persons. PMID- 27270227 TI - Gist in time: Scene semantics and structure enhance recall of searched objects. AB - Previous work has shown that recall of objects that are incidentally encountered as targets in visual search is better than recall of objects that have been intentionally memorized (Draschkow, Wolfe, & Vo, 2014). However, this counter intuitive result is not seen when these tasks are performed with non-scene stimuli. The goal of the current paper is to determine what features of search in a scene contribute to higher recall rates when compared to a memorization task. In each of four experiments, we compare the free recall rate for target objects following a search to the rate following a memorization task. Across the experiments, the stimuli include progressively more scene-related information. Experiment 1 provides the spatial relations between objects. Experiment 2 adds relative size and depth of objects. Experiments 3 and 4 include scene layout and semantic information. We find that search leads to better recall than explicit memorization in cases where scene layout and semantic information are present, as long as the participant has ample time (2500ms) to integrate this information with knowledge about the target object (Exp. 4). These results suggest that the integration of scene and target information not only leads to more efficient search, but can also contribute to stronger memory representations than intentional memorization. PMID- 27270228 TI - Practicing more retrieval routes leads to greater memory retention. AB - A wealth of research has shown that retrieval practice plays a significant role in improving memory retention. The current study focused on one simple yet rarely examined question: would repeated retrieval using two different retrieval routes or using the same retrieval route twice lead to greater long-term memory retention? Participants elaborately learned 22 Japanese-Chinese translation word pairs using two different mediators. Half an hour after the initial study phase, the participants completed two retrieval sessions using either one mediator (Tm1Tm1) or two different mediators (Tm1Tm2). On the final test, which was performed 1week after the retrieval practice phase, the participants received only the cue with a request to report the mediator (M1 or M2) followed by the target (Experiment 1) or only the mediator (M1 or M2) with a request to report the target (Experiment 2). The results of Experiment 1 indicated that the participants who practiced under the Tm1Tm2 condition exhibited greater target retention than those who practiced under the Tm1Tm1 condition. This difference in performance was due to the significant disadvantage in mediator retrieval and decoding of the unpracticed mediator under the Tm1Tm1 condition. Although mediators were provided to participants on the final test in Experiment 2, decoding of the unpracticed mediators remained less effective than decoding of the practiced mediators. We conclude that practicing multiple retrieval routes leads to greater memory retention than focusing on a single retrieval route. Thus, increasing retrieval variability during repeated retrieval practice indeed significantly improves long-term retention in a delay test. PMID- 27270229 TI - Use of a Tissue Engineered Human Skin Model to Investigate the Effects of Wounding and of an Anti-Inflammatory on Melanoma Cell Invasion. AB - An increasing number of studies suggest inflammation stimulates tumour invasion. In melanoma, despite recent advances in targeted therapy and immunomodulatory therapies, this cancer remains difficult to treat. Our previous studies show melanoma cells interact with skin cells in their invasion into tissue engineered skin and suggest inflammation stimulates invasion. The aim of this study was to investigate the use of an anti-inflammatory on melanoma invasion. To do this we developed a wounded and inflamed in vitro 3D melanoma model in which to investigate the use of an anti-inflammatory on melanoma invasion. The tissue engineered skin model was based on human de-epidermised acellular dermis to which keratinocytes, fibroblasts and three different melanoma cell lines were added in various combinations. A simple incisional wound was made in the model and TNF alpha and fibrin were added to simulate conditions of inflammation. Topical ibuprofen in a hydrogel was added and the extent of melanoma invasion into the dermis was assessed under the various conditions. The results showed that penetration of two of the cell lines (HBL and A375SM) into the tissue engineered skin was exacerbated by wounding and ibuprofen significantly decreased invasion of A375SM cells and slightly reduced invasion of HBL cells. A third cell line, C8161, was aggressively invasive under all conditions to an extent that was not influenced by wounding, TNF-alpha or the addition of ibuprofen. In summary, the results for one these cell lines (and a trend for a second cell line) support the hypothesis that a wound environment is conducive to melanoma invasion but the local addition of an anti-inflammatory drug such as ibuprofen may attenuate invasion. PMID- 27270230 TI - Mitochondria-Mediated Anticancer Effects of Non-Thermal Atmospheric Plasma. AB - Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS) since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention. PMID- 27270233 TI - P300 amplitude alterations during inhibitory control in persons with Mild Cognitive Impairment. AB - Deficits in executive function are highly noticeable in Alzheimer's disease, and recent behavioral studies have shown that such deficits - particularly during inhibitory control - can also be found in persons with Mild Cognitive Impairment (MCI). Thus, the objective of this study was to investigate behavioral and electrophysiological correlates of inhibitory control in persons with MCI. A group of persons with MCI and a group healthy older adults performed a Go/NoGo task while electroencephalogram was recorded. Our results revealed that persons with MCI performed less accurately than healthy controls during the Go and NoGo conditions. In addition, we found reduced P300 amplitudes during Go and NoGo conditions relative to healthy older adults. Our results suggest that neurocognitive mechanisms associated with target detection and evaluation (Go P300) and response inhibition (NoGo P300) are compromised in persons with MCI. PMID- 27270234 TI - Antidepressant-like activity of liposomal formulation containing nimodipine treatment in the tail suspension test, forced swim test and MAOB activity in mice. AB - Previous studies have shown that intracellular calcium ion dysfunction may be an etiological factor in affective illness. Nimodipine (NMD) is a Ca(2+) channel blocker that has been extensively investigated for therapy of central nervous system (CNS) disorders. In this work, we have evaluated the antidepressant-like activity of nimodipine encapsulated into liposomes (NMD-Lipo) in mice through tail suspension and forced swim assays, as well as MAOB activity. During the tail suspension test, the administration of NMD-Lipo at 0.1, 1 and 10mg/kg was able to promote a reduction in the immobility time of animals greater than the positive control (imipramine). In the forced swim test, the immobility time of mice treated with NMD-Lipo was reduced. This reduction was significantly greater than that found in the animals treated with imipramine and paroxetine. This may suggest that NMD-Lipo provides more antidepressant-like activity than in positive controls. The groups that received a combination of liposomal NMD and antidepressant drugs showed lower immobility time than the groups, which were treated only with imipramine or paroxetine. The mice treated with the combination of NMD-Lipo and reserpine presented an increase in the time of immobility compared with animals treated only with NMD-Lipo. There was a significant decrease in MAOB activity in animals treated with NMD-Lipo compared with untreated animals. The results of the tail suspension test, forced swim test and MAOB activity suggested that the antidepressant activity of NMD-Lipo may be related to an increase in the cerebral monoamine concentrations. PMID- 27270235 TI - Identification and Analysis of Immunodominant Antigens for ELISA-Based Detection of Theileria annulata. AB - Tropical or Mediterranean theileriosis, caused by the protozoan parasite Theileria annulata, remains an economically important bovine disease in North Africa, Southern Europe, India, the Middle East and Asia. The disease affects mainly exotic cattle and imposes serious constraints upon livestock production and breed improvement programmes. While microscopic and molecular methods exist which are capable of detecting T. annulata during acute infection, the identification of animals in the carrier state is more challenging. Serological tests, which detect antibodies that react against parasite-encoded antigens, should ideally have the potential to identify carrier animals with very high levels of sensitivity and specificity. However, assays developed to date have suffered from a lack of sensitivity and/or specificity and it is, therefore, necessary to identify novel parasite antigens, which can be developed for this purpose. In the present study, genes encoding predicted antigens were bioinformatically identified in the T. annulata genome. These proteins, together with a panel of previously described antigens, were assessed by western blot analysis for immunoreactivity, and this revealed that four novel candidates and five previously described antigens were recognised by immune bovine serum. Using a combination of immunoprecipitation and mass spectrophotometric analysis, an immunodominant protein (encoded by TA15705) was identified as Ta9, a previously defined T cell antigen. Western blotting revealed another of the five proteins in the Ta9 family, TA15710, also to be an immunodominant protein. However, validation by Enzyme-Linked Immunosorbent Assay indicated that due to either allelic polymorphism or differential immune responses of individual hosts, none of the novel candidates can be considered ideal for routine detection of T. annulata-infected/carrier animals. PMID- 27270236 TI - Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis. AB - Platelets play an essential role in hemostasis and wound healing by facilitating thrombus formation at sites of injury. Platelets also mediate inflammation and contain several pro-inflammatory molecules including cytokines and chemokines that mediate leukocyte recruitment and activation. Not surprisingly, platelet dysfunction is known to contribute to several inflammatory disorders. Antiplatelet therapies, such as aspirin, adenosine diphosphate (ADP) antagonists, glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, and anticoagulants such as warfarin, dampen platelet activity at the risk of unwarranted bleeding. Thus, the development of drugs that reduce platelet-mediated inflammation without interfering with thrombus formation is of importance to combat platelet associated disorders. We have shown here for the first time that the tetracycline antibiotic, minocycline, administered to HIV-infected individuals reduces plasma levels of soluble CD40L and platelet factor 4 levels, host molecules predominately released by platelets. Minocycline reduced the activation of isolated platelets in the presence of the potent platelet activator, thrombin, as measured by ELISA and flow cytometry. Platelet degranulation was reduced upon exposure to minocycline as shown by mepacrine retention and flow cytometry. However, minocycline had no effect on spreading, aggregation, GPIIb/IIIa activation, or in vivo thrombus formation. Lastly, immunoblot analysis suggests that the antiplatelet activity of minocycline is likely mediated by inhibition of mixed lineage kinase 3 (MLK3)-p38 MAPK signaling axis and loss of p38 activity. Our findings provide a better understanding of platelet biology and a novel repurposing of an established antibiotic, minocycline, to specifically reduce platelet granule release without affecting thrombosis, which may yield insights in generating novel, specific antiplatelet therapies. PMID- 27270237 TI - Denosumab or Zoledronic Acid in Postmenopausal Women With Osteoporosis Previously Treated With Oral Bisphosphonates. AB - CONTEXT: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. OBJECTIVE: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. DESIGN AND SETTING: This was an international, multicenter, randomized, double-blind trial. PARTICIPANTS: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. INTERVENTIONS: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. MAIN OUTCOME MEASURES: Changes in BMD and bone turnover markers were measured. RESULTS: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). CONCLUSIONS: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL. PMID- 27270238 TI - Ezetimibe-Simvastatin Therapy Reduce Recurrent Ischemic Stroke Risks in Type 2 Diabetic Patients. AB - CONTEXT: Statin is the main lipid-lowering therapy for type 2 diabetes mellitus patients. Recent evidence suggested the cardiovascular protective effects of ezetimibe-simvastatin in acute coronary syndrome patients. OBJECTIVE: To investigate the effect of ezetimibe-simvastatin combination therapy on stroke prevention among diabetic stroke patients. Design, Setting, Participants, and Outcome Measures: This is a retrospective cohort study. Between March 1, 2009 and December 31, 2011, all patients with type 2 diabetes mellitus in Taiwan's National Health Insurance Research Database were screened. Those admitted for ischemic stroke (IS) were recruited and divided into 10-mg ezetimibe-20-mg simvastatin (EZ-SIM), 40-mg atorvastatin (ATOR), and 20-mg simvastatin (SIM) groups for further analyses. The primary outcomes were IS, myocardial infarction, and death from any cause. Patients were followed from index hospitalization to the date of death, loss of follow-up, or study termination. RESULTS: During the 34-month follow-up period, the risk of recurrent IS in the SIM group was higher than that of the ATOR (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.46-2.82) and EZ-SIM (HR, 1.69; 95% CI, 1.14-2.50) groups. The risk of recurrent IS was not significantly lower in the EZ-SIM compared with the ATOR group (HR, 1.20; 95% CI, 0.85-1.69). The incidence of composite endpoint was highest in the SIM group (28.2%), followed by the ATOR (16.1%) and EZ-SIM (15.4%) groups. The multivariate adjusted survival curve showed lower trends of recurrent IS in the EZ-SIM and ATOR groups compared with the SIM group. CONCLUSIONS: High-potency lipid-lowering therapy effectively reduces the risk of recurrent IS in diabetic patients regardless of ATOR or EZ-SIM combination therapy. PMID- 27270239 TI - Transport protein evolution deduced from analysis of sequence, topology and structure. AB - The vast majority of well studied transmembrane channels, secondary carriers, primary active transporters and group translocators are believed to have arisen vis intragenic duplication events from simple channel-forming peptides with just 1-3 transmembrane alpha-helical segments, found ubiquitously in nature. Only a few established channel-forming proteins appear to have evolved via other pathways. The proposed pathway for the evolutionary appearance of the five types of transport proteins involved intragenic duplication of transmembrane pore forming peptide-encoding genes, giving rise to channel proteins. These gave rise to single protein secondary carriers which upon superimposition of addition protein domains and proteins, including energy-coupling proteins and extracytoplasmic receptors, gave rise to multidomain, multicomponent carriers, primary active transporters and group translocators. Some of the largest and best characterized superfamilies of these transmembrane transport proteins are discussed from topological and evolutionary standpoints. PMID- 27270240 TI - Using natural sequences and modularity to design common and novel protein topologies. AB - Protein design is still a challenging undertaking, often requiring multiple attempts or iterations for success. Typically, the source of failure is unclear, and scoring metrics appear similar between successful and failed cases. Nevertheless, the use of sequence statistics, modularity and symmetry from natural proteins, combined with computational design both at the coarse-grained and atomistic levels is propelling a new wave of design efforts to success. Here we highlight recent examples of design, showing how the wealth of natural protein sequence and topology data may be leveraged to reduce the search space and increase the likelihood of achieving desired outcomes. PMID- 27270241 TI - An algorithm for estimation and correction of anisotropic magnification distortion of cryo-EM images without need of pre-calibration. AB - Anisotropic magnification distortion of TEM images (mainly the elliptic distortion) has been recently found as a potential resolution-limiting factor in single particle 3-D reconstruction. Elliptic distortions of ~1-3% have been reported for multiple microscopes under low magnification settings (e.g., 18,000*), which significantly limited the achievable resolution of single particle 3-D reconstruction, especially for large particles. Here we report a generic algorithm that formulates the distortion correction problem as a generalized 2-D alignment task and estimates the distortion parameters directly from the particle images. Unlike the present pre-calibration methods, our computational method is applicable to all datasets collected at a broad range of magnifications using any microscope without need of additional experimental measurements. Moreover, the per-micrograph and/or per-particle level elliptic distortion estimation in our method could resolve potential distortion variations within a cryo-EM dataset, and further improve the 3-D reconstructions relative to constant-value correction by the pre-calibration methods. With successful applications to multiple datasets and cross-validation with the pre-calibration method, we have demonstrated the validity and robustness of our algorithm in estimating the distortion; correction of the elliptic distortion significantly improved the achievable resolutions by ~1-3 folds and enabled 3-D reconstructions of multiple viral structures at 2.4-2.6A resolutions. The resolution limits with elliptic distortion and the amounts of resolution improvements with distortion correction were found to strongly correlate with the product of the particle size and the amount of distortion, which can help assess if elliptic distortion is a major resolution limiting factor for single particle cryo-EM projects. PMID- 27270242 TI - Back to Basics: Is There a Good Reason to Not Systematically Measure Urine Creatinine in Acute Kidney Injury Monitoring? AB - Regardless of the recent advancements in the understanding of the pathophysiology of acute kidney injury (AKI), its diagnosis remains fundamentally dependent on the serum creatinine (sCr) level and urine output (UO), both of which are considered late markers of AKI, offering only a vague idea of the actual creatinine clearance (CrCl). Although not ideal, CrCl is still the most common alternative of the glomerular filtration rate (GFR) in clinical practice. It is generally accepted that early diagnosis of AKI must reveal kidney impairment before sCr increases. Much effort has been made to find tubular and glomerular markers of injury which increase (in blood and/or in urine) before the 'official' diagnosis of AKI. Most of these markers are expensive and not widely available, especially in developing countries. Urine creatinine (CrU), the major link between sCr and UO, has been systematically ignored and clinicians are usually unaware of its value. The reasons for this are unclear, but it may be related to the lack of a reference range, dependence of its concentration value on the urine flow (which in turn is only adequately assessed with an indwelling urinary catheter) and the clinical unavailability of its counterbalance part - creatinine production. Changes in urine tend to precede changes in blood in the course of AKI development and recovery. Hence, it is important to bear in mind that changes in sCr signal renal dysfunction with a significant delay. The search for a more dynamic, 'real-time' but pragmatic assessment of renal function, especially in patients at risk of abrupt decrease in GFR is certainly one of the most relevant focus of research in the field of AKI monitoring. Systematic CrU assessment may be highly relevant in this case. PMID- 27270243 TI - A review of the Generic Design Assessment (GDA) Public Dialogue Pilot (2015) for new nuclear build in the UK: lessons for engagement theory and practice. AB - We have discussed previously that a community-based, asset-based approach is required to achieve any sense of how social sustainability can be defined in a community setting within the context of energy developments. Our approach aims to initiate a lasting change within 'energy' communities through building social capital; focusing on community assets not deficits to define their social priorities. Through deliberation, we develop an understanding of social sustainability so that a community is well placed to enter discussions with government and industry regarding large energy developments that will directly affect them. We review the 2015 Generic Design Assessment (GDA) Public Dialogue Pilot process for potential new nuclear reactors in the UK. We examine the aims of the dialogue, giving particular attention to a comparison between the national sampling of citizens for the GDA and the local community-based, deliberative approach we have proposed previously. We find an ongoing tension between 'national' engagement processes (such as the GDA Public Dialogue Pilot process) and the specific requirements of those energy communities that live adjacent or close to energy infrastructure, manifested here by a conflict between the requirements of the convenor and those of participants regarding priority issues for discussion. We also reveal a paradox; despite participant preference for a remote, internet-based engagement process, they agreed that face to face contact is a priority to encourage trust building between participants and the convenor of the process-a desired outcome of the process. The GDA Public Dialogue Pilot process has demonstrated that stakeholders are willing to engage with and be more directly involved in local energy-related decisions that affect them directly, provided there is opportunity to discuss locally-relevant and site-specific issues in addition to those of a broader nature. There exists a disparity and conflict between 'national' engagement processes and the 'local' priorities of those energy communities that are adjacent or close to energy infrastructure. In this process and others, we have seen an imbalance between the requirements of the convenor and those of participants regarding priority issues for discussion. This continues to be a persistent challenge for those convening stakeholder engagement events where the scope and context is not primarily site-specific. However, it is encouraging that convenors and participants alike continue to be willing to work towards resolving this. PMID- 27270245 TI - Inflammatory Response Using Different Lipid Parenteral Nutrition Formulas in Children After Hematopoietic Stem Cell Transplantation. AB - Nutritional support is an integral part of the supportive care of hematopoietic stem cell transplantation (HSCT) patients. Omega-3 fatty acids (n-3 FA) emulsions in parenteral nutrition (PN) may modify the inflammatory response. The purpose of this study is to compare plasma cytokine levels in children after HSCT using an n 3 FA-containing lipid emulsion (LE) and a soybean oil-based formulation in PN. A randomized double-blind controlled trial was conducted on 14 children following HSCT. Children were randomized to receive either a fish oil or a soybean oil LE. Blood samples were drawn at baseline, on Day 10 and after completion of PN to analyze plasma interleukin 1 beta (IL-1beta), 2 (IL-2), 6 (IL-6), 8 (IL-8), 10 (IL-10), and tumor necrosis factor alpha (TNF-alpha). After 10 days of PN, there were no significant changes in interleukins levels when comparing the two groups or time points (baseline vs. Day 10 of PN). In children requiring PN >21 days, IL 10 and TNF-alpha levels (P <= 0.05) were lower in the fish-oil-containing LE group. Fish oil- and soybean oil-supplemented PN administered for at least 10 days does not cause inflammatory changes. Prolonged PN based on fish oil LE may modulate the inflammatory response. PMID- 27270246 TI - Association between omentin and echo parameters in patients with chronic heart failure. AB - BACKGROUND: Adipose-derived adipokines have been demonstrated to be associated with the development of experimental heart disease through chronic inflammation and cardiac cell apoptosis. Omentin is to be one of the novel adipokines. The aim of this study is to investigate the relationship between circulating omentin and cardiac dysfunction in patients with chronic heart failure (CHF). METHODS: A total of 189 CHF patients were studied, determining serum omentin and echocardiographic parameters. All participants were divided into two experimental groups: the 111 patients who had a left ventricular ejection fraction (EF) >=40% (EF-H) and the 78 patients exhibiting EF values <40% (EF-L). RESULTS: The EF-L group showed significantly higher circulating omentin levels compared to the EF-H group (210.8+/-67.2 vs. 155.3+/-45.3, P<0.001; Student's t-test). Overall, the data of the linear regression analysis revealed that serum omentin levels correlated positively with left atrial diameters (r=0.31, P=0.006), left ventricular end-systolic dimensions (r=0.42, P<0.001), and left ventricular end diastolic dimensions (r=0.38, P=0.002) and negatively with left ventricular EF (r=-0.45, P=0.001; Spearmen's rank correlations coefficients for each). The multiple regression model included all variables at p<0.1 by the univariate analysis. A multiple logistic regression analysis demonstrated that high levels of patients' serum omentin were associated with cardiac dysfunction in patients with CHF (OR=1.22; 95% CI: 0.91-1.58; P=0.009). CONCLUSIONS: These findings suggested that elevated serum omentin levels were only very mildly related to the changes in cardiac volume and function in CHF patients. Further studies are then needed to assess the real clinical value of omentin in this setting. PMID- 27270247 TI - In search of a perennial philosophy for behavioral health integration in primary care. AB - The "perennial philosophy," a concept religious scholars have studied for centuries, represents a search for the values, themes, and constructs that transcend individual religions. Can we who develop and disseminate behavioral health integration in primary care step back from individual models to identify our perennial philosophy? If so, what are the components? What does the evidence tell us? What do we need to learn? Four case examples are presented which represent many patients seen by both of us-a family therapist and a family physician-over our combined 55 years of collaborative practice within integrated primary care settings. Can these patients be cared for in a primary care setting? Our experience provides a simple answer-yes. However, providing care for this range of patients requires variability in team configurations, frequency of visits, lengths of relationships, and interventional strategies. Is there a perennial philosophy of how to design and implement the integration of behavioral health in primary care? We think there should be. we highlight a recent publication from the Eugene S. Farley, Jr. Health Policy Center, entitled "Core Competencies For Behavioral Health Providers Working In Primary Care." The authors purposefully transcend models in delineating eight core competencies. Embedded within these competencies are common or perennial factors. These factors may guide our field going forward, helping us avoid "religious" divisions, seek to understand diverse designs, and embrace integration of models to meet the needs of the populations and teams we serve. (PsycINFO Database Record PMID- 27270248 TI - Simulation-based learning: From theory to practice. AB - Comments on the article, ""Stimulating Reflective Practice Using Collaborative Reflective Training in Breaking Bad News Simulations," by Kim, Hernandez, Lavery, and Denmark (see record 2016-18380-001). Kim et al. are applauded for engaging and supporting the development of simulation-based education, and for their efforts to create an interprofessional learning environment. However, we hope further work on alternate methods of debriefing leverage the already inherent activation of learners that builds on previous experience, fosters reflection and builds skills. What is needed is the transference of learning theories into our educational research efforts that measure the effectiveness, validation, and reliability of behavior based performance change. The majority of breaking bad news (BBN) curricula limit program evaluations to reports of learner satisfaction, confidence and self-efficacy, rather than determining the successful translation of effective and humanistic interpersonal skills into long term clinical practice (Rosenbaum et al., 2004). Research is needed to investigate how educational programs affect provider-patient-family interaction, and ultimately patient and family understanding, to better inform our teaching BBN skills. (PsycINFO Database Record PMID- 27270249 TI - Electronic health records: Context matters! AB - Comments on the article by Kotay, Huang, Jordan, and Korin (see record 2016-22430 001). They tackle how to document patients' social histories in a way that is useful in real-time clinical practice-and explore the implementation of a new electronic health record (EHR) template specifically built to support their residency practice's commitment to addressing the social dimensions of patients' lives. For all of us convinced that the simultaneous integration of the biological, social, psychological, and existential dimensions of care is key to the practice of primary care, there are many questions to explore in relation to using EHRs. How are we going to do this in an environment that preferentially supports particularized data over an engaged awareness of context? How are we going to convince those with the technological expertise and administrative power that the transmission of information alone is not a substitute for insight, meaning, and relationships (Ventres & Frankel, 2010)? And ultimately, how are we going to make sure the EHR works for us instead of against us? Kotay and her colleagues have not answered all these questions in their study-such a task is beyond the abilities of one person or group of researchers- but along with others they have begun to illuminate a way forward (Cifuentes et al., 2015; Glowa Kollisch et al., 2014). May we all now strive to continue the work that these authors have started. (PsycINFO Database Record PMID- 27270250 TI - Locating legacy in illness. AB - The author, a licensed marriage and family therapist, describes her work with Sofia, an eight-year-old Puerto Rican female with chronic and persistent abdominal pain and leg paralysis with no known organic cause. Sofia's mother, Ana, was also seen by the author. Over the course of several weeks, the family shared stories of painful medical procedures and extreme dietary plans prescribed to them by doctors to identify the etiology of Sofia's illness. Ana described her simultaneous relief and frustration when each test result indicated that there was no organic cause for Sofia's debilitating pain. They talked about the push and pull Ana's family experienced as they prayed simultaneously for abnormal and normal test results. The author told Sofia's pediatrician that she would begin to create a community genogram with the family in their next meeting. She explained that the purpose of the community genogram was to illustrate the social and historical contexts of families' lives. They learned that a seminal narrative in Sofia's family legacy connected deep understanding of others with embodiment of their immediate experience. Sofia's illness became one part of her and her family's legacy and cultural tapestry. Ana described the renewed connections that she and Sofia shared with their family members. As Sofia and Ana spoke with their family members more often, Sofia's leg paralysis and stomach pains decreased. Sofia began attending school regularly and visiting less with her pediatrician. (PsycINFO Database Record PMID- 27270251 TI - Hour 25: Neuro ICU. AB - This short story focuses on two patients in a neuro intensive care unit. (PsycINFO Database Record PMID- 27270252 TI - An ode to my uterus. AB - The author of this short story writes about undergoing five surgeries over twenty years to remove endometriosis. She has two children, but without a uterus she wonders if she still is a woman. She is thankful for no more debilitating pain and the freedom to love with creativity and abandon. (PsycINFO Database Record PMID- 27270253 TI - Refugee patients. AB - This short story focuses on refugee patients. Family members talk about the horrific struggles of civil war, refugee camps, and promises of US resettlement. Their harsh reception into a brutal world includes unemployment, food scarcity, and isolation. (PsycINFO Database Record PMID- 27270254 TI - Our stories of illness. AB - In this poem, the author describes three types of stories after healing from his illness: restitution, quest, and chaos. (PsycINFO Database Record PMID- 27270255 TI - On the palliative care unit. AB - As a physician working in palliative care, the author is often privileged to share special moments with patients and their families at the end of life. This haiku poem recalls one such moment in that precious space between life and death, as an elderly woman, surrounded by her adult daughters, takes her last breath. (PsycINFO Database Record PMID- 27270256 TI - Hearts in rhythm. AB - This poem focuses on the author's experience of pregnancy and giving birth, including her first contraction and seeing her baby's heartbeat on the monitor. (PsycINFO Database Record PMID- 27270257 TI - Review of Integrated Psychological Services in Primary Care. AB - Reviews the book, Integrated Psychological Services in Primary Care edited by William Scott Craig (see record 2016-01850-000). This book opens with an article by the editor, in which he outlines the behavioral health needs of primary care patients and the rationale behind integrating mental health services in primary care settings. Subsequent chapters address basic and practical information for a variety of practice locations, such as Patient Centered Medical Home clinics, the Veteran's Administration medical centers, and primary care settings where the concept of integrated health is new. This is an excellent primer for anyone planning to implement an integrated care program or for those considering moving from an independent practice, agency, or traditional health care/hospital environment into an integrated primary care environment. The authors' writing styles made difficult concepts easy to understand and their knowledge of the utility of integration was evident. (PsycINFO Database Record PMID- 27270258 TI - Review of Two Minute Talks to Improve Psychological and Behavioral Health. AB - Reviews the book, Two Minute Talks to Improve Psychological and Behavioral Health by John F. Clabby (see record 2013-13851-002). In this book, the author presents a clear guide to evidence-based brief interventions to improve psychological and behavioral health. Throughout the book the author provides practical tips on brief interventions that are useful for students, beginning practitioners, and seasoned professionals. (PsycINFO Database Record PMID- 27270259 TI - The fourth aim: How do we care for our healthcare workforce? AB - In this column, the president of the Collaborative Family Healthcare Association (CFHA) addresses the question of what the CFHA is doing to create and maintain an engaged, motivated, and satisfied workforce, in the midst of its transformational goals and inherent challenges. The president focuses on three strategies that have the potential to sustain and nurture the people who deliver healthcare. (PsycINFO Database Record PMID- 27270260 TI - Leveraging ultraviolet photodissociation and spectroscopy to investigate peptide and protein three-dimensional structure with mass spectrometry. AB - Recent advances in mass spectrometry and lasers have facilitated the development of novel experiments combining the benefits of both technologies. This minireview focuses on the coupling of visible/ultraviolet photons with mass spectrometry for analysis of peptide and protein three-dimensional structure. Practical aspects of instrument design and the relationship between experiment and theory are discussed. Experiments utilizing spectroscopy, action spectroscopy, excitation energy transfer, photodissociation, and photoactivated radical chemistry are described. The strengths and weaknesses of each approach are discussed in relation to the type of information typically obtained. A significant body of data suggests that under appropriate source conditions, kinetically trapped structures are observed in these experiments rather than true gas phase minima, suggesting retention of solution phase structural features is possible. Further refinement and exploration of these methods promises to accelerate protein structure discovery in the near future. PMID- 27270261 TI - Optimized ultra performance liquid chromatography tandem high resolution mass spectrometry method for the quantification of paraquat in plasma and urine. AB - A simple, sensitive and specific ultra performance liquid chromatography coupled to electrospray tandem high resolution mass spectrometry (UPLC-ESI-HRMS/MS) method has been developed and validated for quantification of paraquat in plasma and urine. The sample preparation was carried out by one-step protein precipitation with acetonitrile. The paraquat was separated with a HILIC column in 10min. Detection was performed using Q Exactive Orbitrap mass spectrometer by Targeted-MS/MS scan mode. Methodological parameters, such as ammonium formate concentration, formic acid concentration, spray voltage, capillary temperature, heater temperature and normalized collision energy were optimized to achieve the highest sensitivity. The calibration curve was linear over the concentration range of LOQ-1000ng/mL. LOD was 0.1 and 0.3ng/mL, LOQ was 0.3 and 0.8ng/mL for urine and plasma, respectively. The intra- and inter-day precisions were <7.97% and 4.78% for plasma and urine. The accuracies were within the range 93.51 100.90%. The plasma and urine matrices had negligible relative matrix effect in this study. This method was successfully applied to determine paraquat concentration in plasma samples with hemoperfusion from 5 suspected paraquat poisoning patients. PMID- 27270262 TI - A simple LC-ESI-MS/MS method for quantification of bacopaside I in rat plasma and its application to a pharmacokinetic study. AB - Bacopaside I is one of the main pseudojujubogenin glycosides isolated from Bacopa monniera. In the present study, a rapid and robust LC-ESI-MS/MS method was developed and validated to quantify bacopaside I in rat plasma. After plasma samples were deproteinized by methanol, the post-treatment samples were analyzed on a Zorbax Eclipse Plus C18 (2.1*50mm, 1.8MUm) column using a mobile phase of acetonitrile and water (65:35, v/v). Detection was performed on a triple quadrupole tandem mass spectrometer with selected reaction monitoring (SRM) mode via electrospray ionization source. This method covered a linearity range of 10 2000ng/mL with the lower limit of quantification of 10ng/mL. The intra- and inter day precisions of analysis were less than 10.2%, and the accuracies were between 11.1% and 8.4% at the concentrations of 25, 150 and 1800ng/mL. The total run time was 6.0min. This method was successfully applied to the preclinical pharmacokinetic study of bacopaside I following intravenous or oral administration to rats. PMID- 27270264 TI - Virtual crystal description of III-V semiconductor alloys in the tight binding approach. AB - We propose a simple and effective approach to construct the empirical tight binding parameters of ternary alloys in the virtual crystal approximation. This combines a new, compact formulation of the strain parameters and a linear interpolation of the Hamiltonians of binary materials strained to the alloy equilibrium lattice parameter. We show that it is possible to obtain a perfect description of the bandgap bowing of ternary alloys in the InGaAsSb family of materials. Furthermore, this approach is in a good agreement with supercell calculations using the same set of parameters. This scheme opens a way for atomistic modeling of alloy-based quantum wells and quantum wires without extensive supercell calculations. PMID- 27270263 TI - A Worthy Finding: Decrease in Total Cholesterol and Low-Density Lipoprotein Cholesterol in Treated Mild Subclinical Hypothyroidism. AB - BACKGROUND: Mild subclinical hypothyroidism (SCH) affects a large number of people and is known to be a risk factor for dyslipidemia. However, whether mild SCH patients should be treated with L-thyroxine to improve lipid profiles remains controversial. In addition, it is also unclear whether all mild SCH patients can benefit from L-thyroxine treatment, regardless of basal thyrotropin or lipid levels. This study aimed to assess the effects of L-thyroxine replacement therapy on the lipid profiles of mild SCH patients. METHODS: This open-label randomized controlled trial was performed in Ningyang County, Shandong Province, China. A total of 378 mild SCH patients with diagnoses confirmed by two thyroid function tests were randomly assigned to either the intervention group (L-thyroxine replacement therapy) or the control group (no treatment). The primary outcome was a change in serum total cholesterol (TC) concentration. RESULTS: In all, 369 participants completed the 15-month follow-up period. Reduced TC concentrations were more prominent in the intervention group than they were in the control group (-0.41 mmol/L vs. -0.17 mmol/L; p = 0.012), and changes in low-density lipoprotein cholesterol levels exhibited the same trend. Subgroup analyses were performed to assess the effects of L-thyroxine in patients with different thyrotropin or TC levels. When the study population was stratified according to basal thyrotropin concentration, all patients who had received L-thyroxine showed reduced TC levels (p < 0.001). The treatment was similarly beneficial for all patients, regardless of basal TC level. Even for subjects with TC levels <5.18 mmol/L, serum TC concentrations remained unchanged in the intervention group (p = 0.936) but increased by 0.35 mmol/L in the control group (p = 0.004). CONCLUSIONS: The findings suggest that mild SCH patients could benefit from L thyroxine treatment to improve lipid profiles, regardless of basal thyrotropin or TC concentrations. PMID- 27270265 TI - [GeSIDA quality care indicators associated with mortality and hospital admission for the care of persons infected by HIV/AIDS]. AB - INTRODUCTION: In 2010, the AIDS Study Group (Grupo de Estudio del SIDA [GESIDA]) developed 66 quality care indicators. The aim of this study is to determine which of these indicators are associated with mortality and hospital admission, and to perform a preliminary assessment of a prediction rule for mortality and hospital admission in patients on treatment and follow-up. METHODS: A retrospective cohort study was conducted in the Hospital Universitario Son Espases (Palma de Mallorca, Spain). Eligible participants were patients with human immunodeficiency syndrome>=18 years old who began follow-up in the Infectious Disease Section between 1 January 2000 and 31 December 2012. A descriptive analysis was performed to evaluate anthropometric variables, and a logistic regression analysis to assess the association between GESIDA indicators and mortality/admission. The mortality probability model was built using logistic regression. RESULTS: A total of 1,944 adults were eligible (median age: 37 years old, 78.8% male). In the multivariate analysis, the quality of care indicators associated with mortality in the follow-up patient group were the items 7, 16 and 20, and in the group of patients on treatment were 7, 16, 20, 35, and 38. The quality of care indicators associated with hospital admissions in the follow-up patients group were the same as those in the mortality analysis, plus number 31. In the treatment group the associated quality of care indicators were items 7, 16, 20, 35, 38, and 40. CONCLUSIONS: Some GeSIDA quality of care indicators were associated with mortality and/or hospital admissions. These indicators are associated with delayed diagnosis, regular monitoring, prevention of infections, and control of comorbidities. PMID- 27270267 TI - Enhanced polysulphide redox reaction using a RuO2 nanoparticle-decorated mesoporous carbon as functional separator coating for advanced lithium-sulphur batteries. AB - A multi-functional RuO2 nanoparticle-embedded mesoporous carbon-coated separator is used as an electrocatalytic and adsorbing polysulphide-net to enhance the redox reaction of migrating polysulphides, to improve active material utilization and boost the electrochemical performance of lithium-sulphur batteries. PMID- 27270266 TI - Comparison of cerebral blood flow and structural penumbras in relation to white matter hyperintensities: A multi-modal magnetic resonance imaging study. AB - Normal-appearing white matter (NAWM) surrounding WMHs is associated with decreased structural integrity and perfusion, increased risk of WMH growth, and is referred to as the WMH penumbra. Studies comparing structural and cerebral blood flow (CBF) penumbras within the same individuals are lacking, however, and would facilitate our understanding of mechanisms resulting in WM damage. This study aimed to compare both CBF and structural WMH penumbras in non-demented aging. Eighty-two elderly volunteers underwent 3T-MRI including fluid attenuated inversion recovery (FLAIR), pulsed arterial spin labeling and diffusion tensor imaging (DTI). A NAWM layer mask was generated for periventricular and deep WMHs. Mean CBF, DTI-fractional anisotropy (DTI-FA), DTI-mean diffusivity (DTI-MD) and FLAIR intensity for WMHs and its corresponding NAWM layer masks were computed and compared against its mean within total brain NAWM using mixed effects models. For both periventricular and deep WMHs, DTI-FA, DTI-MD and FLAIR intensity changes extended 2-9 mm surrounding WMHs (p <= 0.05), while CBF changes extended 13-14 mm (p <= 0.05). The CBF penumbra is more extensive than structural penumbras in relation to WMHs and includes WM tissue both with and without microstructural changes. Findings implicate CBF as a potential target for the prevention of both micro and macro structural WM damage. PMID- 27270268 TI - Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine. AB - BACKGROUND: Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. RESULTS: Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP-EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP-EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. CONCLUSIONS: Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway. PMID- 27270269 TI - Asthma in Children With Comorbid Obesity: Intervention Development in a High-Risk Urban Community. AB - This article describes formative work conducted to inform design of an intervention targeting asthma control in overweight/obese children. Using a PRECEDE-PROCEED framework and a community-based participatory research approach, investigators conducted key informant interviews and focus groups in a low-income urban community. Key informants (N = 18) represented schools and community agencies. Focus groups were conducted with caregivers (4 groups, N = 31) and children (3 groups, N = 30). Focus group participants were low-income and African American, Puerto Rican, or Mexican. Children were age 5 to 12 years and overweight or obese with a diagnosis of asthma; caregivers had a child meeting these criteria. A range of issues competed with families' day-to-day prioritization and management of asthma, with social limitations reported as the most important issue. Many school-level and individual-level barriers were described. Caregivers and children drew strong connections between asthma and obesity and described their need to comanage these conditions. The connection between the diseases was not as obvious for the key informants, many of whom control the services families receive. These results led to an understanding of key targets and components that are needed for a multilevel community-based intervention to be relevant and appropriate in low-income children with both asthma and obesity. PMID- 27270270 TI - Consumers' role in mental health care: a research perspective. PMID- 27270272 TI - MicroRNA-137 Affects Proliferation and Migration of Placenta Trophoblast Cells in Preeclampsia by Targeting ERRalpha. AB - OBJECTIVE: To investigate the effects of microRNA-137 (miRNA-137) in proliferation and migration of placenta trophoblast cells of preeclampsia and the targeting gene of miRNA-137. METHODS: A total of 134 cases of puerperants were divided into normal pregnancy (n = 50), mild preeclampsia (n = 38), and severe preeclampsia groups (n = 46). MiRNA-137, estrogen-related receptor alpha (ERRalpha), and wingless INT (WNT)11 messenger RNAs (mRNAs) were measured in placental tissue and trophoblast cells after transfection, and ERRalpha protein in placental tissues was detected by immunohistochemistry. The target genes of miRNA-137, trophoblast cell proliferation, migration, and invasion abilities were detected. Both ERRalpha and WNT11 proteins in the trophoblast cells were measured after transfection. RESULT: Relative expressions of miRNA-137 were higher, and positive expression rates and relative expression levels of ERRalpha protein were lower in mild and severe preeclampsia and early- and late-onset preeclampsia than in normal pregnancy group (all P < .05). MiRNA-137 in the placental tissues was negatively correlated with ERRalpha protein ( P < .05). Luciferase reporter gene assay analysis showed that ERRalpha was a direct target gene of miRNA-137. Absorbance values, relative scratch-covered areas, cell membrane permeable rate, ERRalpha, and WNT11 mRNA and protein relative expressions were significantly lower, while cells at G1/G0 phase were higher in miRNA-137 mimic group than those in the blank, negative control, and miRNA-137 inhibitor group. CONCLUSION: MiRNA 137 significantly reduced the proliferation and migration of placenta trophoblast cells of preeclampsia by targeting ERRalpha, which might be a potential target for gene therapy. PMID- 27270271 TI - Computerized assessment of goal-directed behavior in Parkinson's disease. AB - INTRODUCTION: Apathy is a syndrome characterized by a reduction in goal-directed behavior. Neurodegenerative diseases frequently exhibit apathy. However, we lack an objective measure of apathy. The Philadelphia Apathy Computerized Task (PACT) measures impairments in goal-directed behavior that contribute to apathy, including initiation, planning, and motivation. We sought to examine these mechanisms in Parkinson's disease (PD) patients. METHOD: PD patients and healthy controls with a caregiver were recruited for the study. Participants were administered the PACT, a novel computerized assessment of goal-directed behavior based on reaction times, and the Starkstein Apathy Scale (AS). Care partners completed the Neuropsychiatric Inventory (NPI). Baseline demographic characteristics of PD and control participants were compared using t tests and Wilcoxon rank sum tests. Linear regressions were used to compare PD patients to controls on each of the three PACT subtasks (initiation, planning, and motivation) while controlling for motor slowing. We then compared performance on each PACT subtask between PD subjects defined as apathetic using the NPI and Starkstein Apathy Scale and controls. RESULTS: We included 30 PD and 15 control participants in the analysis. When controlling for motor slowing, both all PD and PD apathetic subjects were significantly slower than controls on the planning task and on the initiation task. There were no significant differences between PD patients and controls on the motivation tasks. CONCLUSIONS: PD patients showed specific initiation and planning deficits compared to control participants. After using traditional scales to define apathy, PD apathetic patients still exhibited impaired initiation and planning behaviors. These results suggest that the PACT measures aspects of impaired goal-directed behavior that may contribute to apathy in PD. PMID- 27270273 TI - Truncated type IV pilin PilA(108) activates the intramembrane protease AlgW to cleave MucA and PilA(108) itself in vitro. AB - For alginate production in Pseudomonas aeruginosa, the intramembrane protease AlgW must be activated to cleave the periplasmic domain of anti-sigma factor MucA for release of the sequestered ECF sigma factor AlgU. Previously, we reported that three tandem point mutations in the pilA gene, resulting in a truncated type IV pilin termed PilA(108) with a C-terminal motif of phenylalanine-threonine phenylalanine (FTF), induced mucoidy in strain PAO579. In this study, we purified PilA(108) protein and synthesized a peptide 'SGAGDITFTF' corresponding to C terminus of PilA(108) and found they both caused the degradation of MucA by AlgW. Interestingly, AlgW could also cleave PilA(108) between alanine(62) and glycine(63) residues. Overexpression of the recombinant FTF motif-bearing MucE protein, originally a small periplasmic polypeptide with the C-terminal motif WVF, could induce mucoid conversion in the PAO1 strain. In all, our results provided a model of activation of AlgW by another protein ending with proper motifs. Our data suggest that in addition to MucA cleavage, AlgW may cleave other substrates. PMID- 27270274 TI - Relationship between Fosfomycin Exposure and Amplification of Escherichia coli Subpopulations with Reduced Susceptibility in a Hollow-Fiber Infection Model. AB - Understanding the relationship between antibiotic exposure and amplification of bacterial subpopulations with reduced drug susceptibility over time is important for evaluating the adequacy of dosing regimens. We utilized a hollow-fiber infection model to identify the fosfomycin intravenous dosing regimens that prevented the amplification of Escherichia coli bacterial subpopulations with reduced fosfomycin susceptibility. The challenge isolate was E. coli ATCC 25922 (agar MIC with glucose-6-phosphate, 1 mg/liter; agar MIC without glucose-6 phosphate, 32 mg/liter). The fosfomycin dosing regimens studied were 1 to 12 g every 8 h for 10 days to approximate that planned for clinical use. The studies included a no-treatment control regimen. Two bacterial subpopulations were identified, one with reduced susceptibility with agar MIC values ranging from 32 to 128 mg/liter and the other resistant with agar MIC values of 256 to >1,024 mg/liter on plates containing 5* and 256* the baseline MIC value, respectively. An inverted-U-shaped function best described the relationship between the amplification of the two bacterial subpopulations and drug exposure. The lowest fosfomycin dosing regimen that did not amplify a bacterial subpopulation with reduced susceptibility was 4 g administered every 8 h. Nearly immediate amplification of bacterial subpopulations with reduced susceptibility was observed with fosfomycin dosing regimens consisting of 1 to 2 g every 8 h. These data will be useful to support the selection of fosfomycin dosing regimens that minimize the potential for on-therapy amplification of bacterial subpopulations with reduced susceptibility. PMID- 27270275 TI - Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients. AB - The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults. PMID- 27270276 TI - Revisiting the Concept of Targeting Only Bacillus anthracis Toxins as a Treatment for Anthrax. AB - Protective antigen (PA)-based vaccines are effective in preventing the development of fatal anthrax disease both in humans and in relevant animal models. The Bacillus anthracis toxins lethal toxin (lethal factor [LF] plus PA) and edema toxin (edema factor [EF] plus PA) are essential for the establishment of the infection, as inactivation of these toxins results in attenuation of the pathogen. Since the toxins reach high toxemia levels at the bacteremic stages of the disease, the CDC's recommendations include combining antibiotic treatment with antitoxin (anti-PA) immunotherapy. We demonstrate here that while treatment with a highly potent neutralizing monoclonal antibody was highly efficient as postexposure prophylaxis treatment, it failed to protect rabbits with any detectable bacteremia (>=10 CFU/ml). In addition, we show that while PA vaccination was effective against a subcutaneous spore challenge, it failed to protect rabbits against systemic challenges (intravenous injection of vegetative bacteria) with the wild-type Vollum strain or a toxin-deficient mutant. To test the possibility that additional proteins, which are secreted by the bacteria under pathogenicity-stimulating conditions in vitro, may contribute to the vaccine's potency, we immunized rabbits with a secreted protein fraction from a toxin-null mutant. The antiserum raised against the secreted fraction reacts with the bacteria in an immunofluorescence assay. Immunization with the secreted protein fraction did not protect the rabbits against a systemic challenge with the fully pathogenic bacteria. Full protection was obtained only by a combined vaccination with PA and the secreted protein fraction. Therefore, these results indicate that an effective antiserum treatment in advanced stages of anthrax must include toxin-neutralizing antibodies in combination with antibodies against bacterial cell targets. PMID- 27270277 TI - Antimalarial Benzoxaboroles Target Plasmodium falciparum Leucyl-tRNA Synthetase. AB - There is a need for new antimalarials, ideally with novel mechanisms of action. Benzoxaboroles have been shown to be active against bacteria, fungi, and trypanosomes. Therefore, we investigated the antimalarial activity and mechanism of action of 3-aminomethyl benzoxaboroles against Plasmodium falciparum Two 3 aminomethyl compounds, AN6426 and AN8432, demonstrated good potency against cultured multidrug-resistant (W2 strain) P. falciparum (50% inhibitory concentration [IC50] of 310 nM and 490 nM, respectively) and efficacy against murine Plasmodium berghei infection when administered orally once daily for 4 days (90% effective dose [ED90], 7.4 and 16.2 mg/kg of body weight, respectively). To characterize mechanisms of action, we selected parasites with decreased drug sensitivity by culturing with stepwise increases in concentration of AN6426. Resistant clones were characterized by whole-genome sequencing. Three generations of resistant parasites had polymorphisms in the predicted editing domain of the gene encoding a P. falciparum leucyl-tRNA synthetase (LeuRS; PF3D7_0622800) and in another gene (PF3D7_1218100), which encodes a protein of unknown function. Solution of the structure of the P. falciparum LeuRS editing domain suggested key roles for mutated residues in LeuRS editing. Short incubations with AN6426 and AN8432, unlike artemisinin, caused dose-dependent inhibition of [(14)C]leucine incorporation by cultured wild-type, but not resistant, parasites. The growth of resistant, but not wild-type, parasites was impaired in the presence of the unnatural amino acid norvaline, consistent with a loss of LeuRS editing activity in resistant parasites. In summary, the benzoxaboroles AN6426 and AN8432 offer effective antimalarial activity and act, at least in part, against a novel target, the editing domain of P. falciparum LeuRS. PMID- 27270278 TI - Detection of Colistin Resistance Gene mcr-1 in Hypervirulent Klebsiella pneumoniae and Escherichia coli Isolates from an Infant with Diarrhea in China. PMID- 27270279 TI - Influence of Renal Replacement Modalities on Amikacin Population Pharmacokinetics in Critically Ill Patients on Continuous Renal Replacement Therapy. AB - The objective of this study was to describe amikacin pharmacokinetics (PK) in critically ill patients receiving equal doses (30 ml/kg of body weight/h) of continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF). Patients receiving amikacin and undergoing CVVH or CVVHDF were eligible. Population pharmacokinetic analysis and Monte Carlo simulation were undertaken using the Pmetrics software package for R. Sixteen patients (9 undergoing CVVH, 11 undergoing CVVHDF) and 20 sampling intervals were analyzed. A two-compartment linear model best described the data. Patient weight was the only covariate that was associated with drug clearance. The mean +/- standard deviation parameter estimates were 25.2 +/- 17.3 liters for the central volume, 0.89 +/- 1.17 h(-1) for the rate constant for the drug distribution from the central to the peripheral compartment, 2.38 +/- 6.60 h(-1) for the rate constant for the drug distribution from the peripheral to the central compartment, 4.45 +/- 2.35 liters/h for hemodiafiltration clearance, and 4.69 +/- 2.42 liters/h for hemofiltration clearance. Dosing simulations for amikacin supported the use of high dosing regimens (>=25 mg/kg) and extended intervals (36 to 48 h) for most patients when considering PK/pharmacodynamic (PD) targets of a maximum concentration in plasma (Cmax)/MIC ratio of >=8 and a minimal concentration of <=2.5 mg/liter at the end of the dosing interval. The mean clearance of amikacin was 1.8 +/- 1.3 liters/h by CVVHDF and 1.3 +/- 1 liters/h by CVVH. On the basis of simulations, a strategy of an extended-interval high loading dose of amikacin (25 mg/kg every 48 h) associated with therapeutic drug monitoring (TDM) should be the preferred approach for aminoglycoside treatment in critically ill patients receiving continuous renal replacement therapy (CRRT). (This study is a substudy of a trial registered at ClinicalTrials.gov under number NCT01403220.). PMID- 27270280 TI - In Vitro Activity of Fusidic Acid-Containing Combinations against Carbapenem Resistant Acinetobacter baumannii Clinical Strains. PMID- 27270281 TI - Development and Evaluation of a Gentamicin Pharmacokinetic Model That Facilitates Opportunistic Gentamicin Therapeutic Drug Monitoring in Neonates and Infants. AB - Trough gentamicin therapeutic drug monitoring (TDM) is time-consuming, disruptive to neonatal clinical care, and a patient safety issue. Bayesian models could allow TDM to be performed opportunistically at the time of routine blood tests. This study aimed to develop and prospectively evaluate a new gentamicin model and a novel Bayesian computer tool (neoGent) for TDM use in neonatal intensive care. We also evaluated model performance for predicting peak concentrations and the area under the concentration-time curve from time 0 h to time t h (AUC0- t). A pharmacokinetic meta-analysis was performed on pooled data from three studies (1,325 concentrations from 205 patients). A 3-compartment model was used with the following covariates: allometric weight scaling, postmenstrual and postnatal age, and serum creatinine concentration. Final parameter estimates (standard errors) were as follows: clearance, 6.2 (0.3) liters/h/70 kg of body weight; central volume (V), 26.5 (0.6) liters/70 kg; intercompartmental disposition (Q), 2.2 (0.3) liters/h/70 kg; peripheral volume V2, 21.2 (1.5) liters/70 kg; intercompartmental disposition (Q2), 0.3 (0.05) liters/h/70 kg; peripheral volume V3, 148 (52.0) liters/70 kg. The model's ability to predict trough concentrations from an opportunistic sample was evaluated in a prospective observational cohort study that included data from 163 patients and 483 concentrations collected in five hospitals. Unbiased trough predictions were obtained; the median (95% confidence interval [CI]) prediction error was 0.0004 (-1.07, 0.84) mg/liter. Results also showed that peaks and AUC0- t values could be predicted (from one randomly selected sample) with little bias but relative imprecision, with median (95% CI) prediction errors being 0.16 (-4.76, 5.01) mg/liter and 10.8 (-24.9, 62.2) mg . h/liter, respectively. neoGent was implemented in R/NONMEM and in the freely available TDMx software. PMID- 27270283 TI - Validation and Application of a Dried Blood Spot Assay for Biofilm-Active Antibiotics Commonly Used for Treatment of Prosthetic Implant Infections. AB - Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des RIF, CIP, and FUS in DBS were 15 MUg/liter, 14 MUg/liter, 25 MUg/liter, and 153 MUg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4 degrees C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections. PMID- 27270282 TI - Substrate Inhibition of VanA by d-Alanine Reduces Vancomycin Resistance in a VanX Dependent Manner. AB - The increasing resistance of clinical pathogens against the glycopeptide antibiotic vancomycin, a last-resort drug against infections with Gram-positive pathogens, is a major problem in the nosocomial environment. Vancomycin inhibits peptidoglycan synthesis by binding to the d-Ala-d-Ala terminal dipeptide moiety of the cell wall precursor lipid II. Plasmid-transferable resistance is conferred by modification of the terminal dipeptide into the vancomycin-insensitive variant d-Ala-d-Lac, which is produced by VanA. Here we show that exogenous d-Ala competes with d-Lac as a substrate for VanA, increasing the ratio of wild-type to mutant dipeptide, an effect that was augmented by several orders of magnitude in the absence of the d-Ala-d-Ala peptidase VanX. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that high concentrations of d-Ala led to the production of a significant amount of wild-type cell wall precursors, while vanX null mutants produced primarily wild-type precursors. This enhanced the efficacy of vancomycin in the vancomycin-resistant model organism Streptomyces coelicolor, and the susceptibility of vancomycin-resistant clinical isolates of Enterococcus faecium (VRE) increased by up to 100-fold. The enhanced vancomycin sensitivity of S. coelicolor cells correlated directly to increased binding of the antibiotic to the cell wall. Our work offers new perspectives for the treatment of diseases associated with vancomycin-resistant pathogens and for the development of drugs that target vancomycin resistance. PMID- 27270284 TI - Physiologically Based Pharmacokinetic Model of Rifapentine and 25-Desacetyl Rifapentine Disposition in Humans. AB - Rifapentine (RPT) is a rifamycin antimycobacterial and, as part of a combination therapy, is indicated for the treatment of pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis Although the results from a number of studies indicate that rifapentine has the potential to shorten treatment duration and enhance completion rates compared to other rifamycin agents utilized in antituberculosis drug regimens (i.e., regimens 1 to 4), its optimal dose and exposure in humans are unknown. To help inform such an optimization, a physiologically based pharmacokinetic (PBPK) model was developed to predict time course, tissue specific concentrations of RPT and its active metabolite, 25-desacetyl rifapentine (dRPT), in humans after specified administration schedules for RPT. Starting with the development and verification of a PBPK model for rats, the model was extrapolated and then tested using human pharmacokinetic data. Testing and verification of the models included comparisons of predictions to experimental data in several rat tissues and time course RPT and dRPT plasma concentrations in humans from several single- and repeated-dosing studies. Finally, the model was used to predict RPT concentrations in the lung during the intensive and continuation phases of a current recommended TB treatment regimen. Based on these results, it is anticipated that the PBPK model developed in this study will be useful in evaluating dosing regimens for RPT and for characterizing tissue-level doses that could be predictors of problems related to efficacy or safety. PMID- 27270285 TI - Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria. AB - Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV. PMID- 27270286 TI - Serum Albumin and Ca2+ Are Natural Competence Inducers in the Human Pathogen Acinetobacter baumannii. AB - The increasing frequency of bacteria showing antimicrobial resistance (AMR) raises the menace of entering into a postantibiotic era. Horizontal gene transfer (HGT) is one of the prime reasons for AMR acquisition. Acinetobacter baumannii is a nosocomial pathogen with outstanding abilities to survive in the hospital environment and to acquire resistance determinants. Its capacity to incorporate exogenous DNA is a major source of AMR genes; however, few studies have addressed this subject. The transformation machinery as well as the factors that induce natural competence in A. baumannii are unknown. In this study, we demonstrate that naturally competent strain A118 increases its natural transformation frequency upon the addition of Ca(2+)or albumin. We show that comEA and pilQ are involved in this process since their expression levels are increased upon the addition of these compounds. An unspecific protein, like casein, does not reproduce this effect, showing that albumin's effect is specific. Our work describes the first specific inducers of natural competence in A. baumannii Overall, our results suggest that the main protein in blood enhances HGT in A. baumannii, contributing to the increase of AMR in this threatening human pathogen. PMID- 27270287 TI - Pyrazinamide Is Active against Mycobacterium tuberculosis Cultures at Neutral pH and Low Temperature. AB - For the past decades, an acidic pH has been used to render Mycobacterium tuberculosis susceptible to pyrazinamide for in vitro testing. Here, we show that at the standard breakpoint concentration and reduced culture temperatures, pyrazinamide (PZA) is active against tuberculosis (TB) at neutral pH. This finding should help unravel the mechanism of action of PZA and allow drug susceptibility testing (DST) methods to be optimized. PMID- 27270288 TI - Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii. AB - LpxC inhibitors have generally shown poor in vitro activity against Acinetobacter baumannii We show that the LpxC inhibitor PF-5081090 inhibits lipid A biosynthesis, as determined by silver staining and measurements of endotoxin levels, and significantly increases cell permeability. The presence of PF-5081090 at 32 mg/liter increased susceptibility to rifampin, vancomycin, azithromycin, imipenem, and amikacin but had no effect on susceptibility to ciprofloxacin and tigecycline. Potentiating existing antibiotics with LpxC inhibitors may represent an alternative treatment strategy for multidrug-resistant A. baumannii. PMID- 27270290 TI - In Vitro Characterization of Human Cytomegalovirus-Targeting Therapeutic Monoclonal Antibodies LJP538 and LJP539. AB - Human cytomegalovirus (HCMV) infection is usually benign in healthy individuals but can cause life-threatening disease in those with compromised immune systems. Approved drugs available to treat HCMV disease, including ganciclovir, cidofovir, and foscarnet, have significant toxicities that limit their use in certain patient populations. LJP538 and LJP539 are human monoclonal antibodies that are being evaluated as immunoglobulin therapeutics. The antibodies target glycoproteins gB and the gH/gL/UL128/UL130/UL131a pentameric complex, respectively. Here we present an in vitro characterization of these antibodies. We show that LJP538 and LJP539 are more potent than a marketed immunoglobulin at inhibiting HCMV infection of various cell lines relevant to pathogenesis. We find that LJP538 and LJP539 are active against a panel of clinical isolates in vitro and demonstrate minor-to-moderate synergy in combination. Passage of HCMV in the presence of LJP538 or LJP539 alone resulted in resistance-associated mutations that mapped to the target genes. However, no loss of susceptibility to the combination of antibodies was observed for >400 days in culture. Finally, the binding regions of LJP538 and LJP539 are conserved among clinical isolates. Taken together, these data support the use of LJP538 and LJP539 in combination for clinical trials in HCMV patients. PMID- 27270289 TI - Horizontal Transfer of Carbapenemase-Encoding Plasmids and Comparison with Hospital Epidemiology Data. AB - Carbapenemase-producing organisms have spread worldwide, and infections with these bacteria cause significant morbidity. Horizontal transfer of plasmids carrying genes that encode carbapenemases plays an important role in the spread of multidrug-resistant Gram-negative bacteria. Here we investigate parameters regulating conjugation using an Escherichia coli laboratory strain that lacks plasmids or restriction enzyme modification systems as a recipient and also using patient isolates as donors and recipients. Because conjugation is tightly regulated, we performed a systematic analysis of the transfer of Klebsiella pneumoniae carbapenemase (blaKPC)-encoding plasmids into multiple strains under different environmental conditions to investigate critical variables. We used four blaKPC-carrying plasmids isolated from patient strains obtained from two hospitals: pKpQIL and pKPC-47e from the National Institutes of Health, and pKPC_UVA01 and pKPC_UVA02 from the University of Virginia. Plasmid transfer frequency differed substantially between different donor and recipient pairs, and the frequency was influenced by plasmid content, temperature, and substrate, in addition to donor and recipient strain. pKPC-47e was attenuated in conjugation efficiency across all conditions tested. Despite its presence in multiple clinical species, pKPC_UVA01 had lower conjugation efficiencies than pKpQIL into recipient strains. The conjugation frequency of these plasmids into K. pneumoniae and E. coli patient isolates ranged widely without a clear correlation with clinical epidemiological data. Our results highlight the importance of each variable examined in these controlled experiments. The in vitro models did not reliably predict plasmid mobilization observed in a patient population, indicating that further studies are needed to understand the most important variables affecting horizontal transfer in vivo. PMID- 27270291 TI - Outcome of childhood-onset full-house nephropathy. AB - Background: Patients with full-house nephropathy (FHN) present renal lesions that are indistinguishable from those of lupus nephritis (LN) but lack the systemic features necessary to meet diagnostic criteria for systemic lupus erithematosus (SLE). Some have been reported to develop a delayed SLE with time. The clinical outcome of children having FHN without SLE has never been reported. Methods: Children with biopsy-proven FHN were selected after excluding SLE cases by the absence of America College of Rheumatology criteria. The proportion of patients with complete (proteinuria <0.5 g/day) or partial remission (proteinuria <=50% from baseline), relapse (estimated glomerular filtration rate <25% and/or proteinuria >=50% from baseline) and progression to Stage III chronic kidney disease (CKD) was described according to age and gender groups with the Kaplan Meier curve and compared with the Log-rank test. Entity of treatment was summarized by a score at induction (0-6 months) and maintenance (6-18 months). Cox-regression model was performed to test predictors of remission, relapse and progression to CKD. Results: Among 42 patients (28 pre-pubertal) who met the inclusion criteria, 39 (92.9%) achieved partial and 32 (76.2%) complete remission of nephropathy over 2.78 and 7.51 months of follow-up. At 10 years, the probability of progressing to CKD was 4.8%. Of those achieving remission, 18% had a renal flare mainly within 4 years after remission. Pre-pubertal males achieved complete remission more frequently than other patients but often relapsed; pre pubertal females were treated more aggressively. Cox-regression analysis did not find independent predictors of remission or relapse. Conclusions: The outcome of the patients with FHN we investigated was encouraging. Recurrences are limited to the first 4 years following diagnosis, allowing progressive withdrawal of immunosuppression in patients achieving remission. Evaluation of risk factors for adverse outcome is necessary especially in pre-pubertal children. PMID- 27270292 TI - Association between changes in quality of life and mortality in hemodialysis patients: results from the DOPPS. AB - Background: Cross-sectional health-related quality of life (HR-QOL) measures are associated with mortality in hemodialysis (HD) patients. The impact of changes in HR-QOL on outcomes remains unclear. We describe the association of prior changes in HR-QOL with subsequent mortality among HD patients. Methods: A total of 13 784 patients in the Dialysis Outcomes and Practice Patterns Study had more than one measurement of HR-QOL. The impact of changes between two measurements of the physical (PCS) and mental (MCS) component summary scores of the SF-12 on mortality was estimated with Cox regression. Results: Mean age was 62 years (standard deviation: 14 years); 59% were male and 32% diabetic. Median time between HR-QOL measurements was 12 months [interquartile range (IQR): 11, 14]. Median initial PCS and MCS scores were 37.5 (IQR: 29.4, 46.2) and 46.4 (IQR: 37.2, 54.9); median changes in PCS and MCS scores were -0.2 (IQR: -5.5, 4.7) and 0.1 (IQR: -6.8, 5.9), respectively. The adjusted hazard ratio (HR) for a 5-point decline in HR-QOL score was 1.09 [95% confidence interval (CI): 1.06-1.12] for PCS and 1.05 (95% CI: 1.03-1.08) for MCS. Adjusting for the second QOL score, the change was not associated with mortality: HR = 1.01 (95% CI: 0.98-1.05) for delta PCS and 1.01 (95% CI: 0.98-1.03) for delta MCS. Categorizing the first and second scores as predictors, only the second PCS or MCS score was associated with mortality. Conclusions: In our study, only the most recent HR-QOL score was associated with mortality. Hence, the predictive power of a measurement of HR-QOL is not affected by changes in HR-QOL prior to that measurement; more frequent HR QOL measurements are needed to improve the prediction of outcomes in HD. Further studies are needed to determine the optimal frequency and appropriate instrument to be used for serial measurements. PMID- 27270294 TI - Analysis of self-assembly of S-layer protein slp-B53 from Lysinibacillus sphaericus. AB - The formation of stable and functional surface layers (S-layers) via self assembly of surface-layer proteins on the cell surface is a dynamic and complex process. S-layers facilitate a number of important biological functions, e.g., providing protection and mediating selective exchange of molecules and thereby functioning as molecular sieves. Furthermore, S-layers selectively bind several metal ions including uranium, palladium, gold, and europium, some of them with high affinity. Most current research on surface layers focuses on investigating crystalline arrays of protein subunits in Archaea and bacteria. In this work, several complementary analytical techniques and methods have been applied to examine structure-function relationships and dynamics for assembly of S-layer protein slp-B53 from Lysinibacillus sphaericus: (1) The secondary structure of the S-layer protein was analyzed by circular dichroism spectroscopy; (2) Small angle X-ray scattering was applied to gain insights into the three-dimensional structure in solution; (3) The interaction with bivalent cations was followed by differential scanning calorimetry; (4) The dynamics and time-dependent assembly of S-layers were followed by applying dynamic light scattering; (5) The two dimensional structure of the paracrystalline S-layer lattice was examined by atomic force microscopy. The data obtained provide essential structural insights into the mechanism of S-layer self-assembly, particularly with respect to binding of bivalent cations, i.e., Mg2+ and Ca2+. Furthermore, the results obtained highlight potential applications of S-layers in the fields of micromaterials and nanobiotechnology by providing engineered or individual symmetric thin protein layers, e.g., for protective, antimicrobial, or otherwise functionalized surfaces. PMID- 27270295 TI - Percutaneous internal ring suturing as a first choice laparoscopic inguinal hernia repair method in girls: a single-center study in 148 patients. AB - INTRODUCTION: We sought to retrospectively assess the operative findings and clinical outcomes of 148 girls who underwent laparoscopic inguinal hernia repair with the percutaneous internal ring suturing (PIRS) technique. METHODS: Between 2010 and 2014, girls with inguinal hernia underwent surgery using the laparoscopic PIRS technique described by Patkowski. Demographic and perioperative findings, complications, and recurrences were evaluated. RESULTS: A total of 205 inguinal hernia repairs were performed in 148 children with a mean age of 5.83 years (1 month-16 years). In 57 girls (38.5 %), the hernias were bilaterally repaired, while in 91 girls (61.5 %) hernias were unilaterally repaired. The mean follow-up time was 3.6 years (range 2.5-6.1 years). No serious complications or recurrence were noted. Granuloma occurred in one patient. CONCLUSION: The PIRS technique is a safe, simple and effective procedure for girls. Excellent cosmetic results and reduced recurrence rates are associated with this method. This procedure is particularly suitable for girls because they lack a spermatic cord and vascular structures that can cause complications with this technique in boys. Based on our experience and others in the literature, we suggest that the PIRS procedure might be considered a gold standard for inguinal hernia operations in girls. PMID- 27270293 TI - Relationship of proximal tubular injury to chronic kidney disease as assessed by urinary kidney injury molecule-1 in five cohort studies. AB - BACKGROUND: The primary biomarkers used to define CKD are serum creatinine and albuminuria. These biomarkers have directed focus on the filtration and barrier functions of the kidney glomerulus even though albuminuria results from tubule dysfunction as well. Given that proximal tubules make up ~90% of kidney cortical mass, we evaluated whether a sensitive and specific marker of proximal tubule injury, urinary kidney injury molecule-1 (KIM-1), is elevated in individuals with CKD or with risk factors for CKD. METHODS: We measured urinary KIM-1 in participants of five cohort studies from the USA and Sweden. Participants had a wide range of kidney function and were racially and ethnically diverse. Multivariable linear regression models were used to test the association of urinary KIM-1 with demographic, clinical and laboratory values. RESULTS: In pooled, multivariable-adjusted analyses, log-transformed, creatinine-normalized urinary KIM-1 levels were higher in those with lower eGFR {beta = -0.03 per 10 mL/min/1.73 m(2) [95% confidence interval (CI) -0.05 to -0.02]} and greater albuminuria [beta = 0.16 per unit of log albumin:creatinine ratio (95% CI 0.15 0.17)]. Urinary KIM-1 levels were higher in current smokers, lower in blacks than nonblacks and lower in users versus nonusers of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. CONCLUSION: Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD. PMID- 27270296 TI - Synthetic Morphogenesis. AB - Throughout biology, function is intimately linked with form. Across scales ranging from subcellular to multiorganismal, the identity and organization of a biological structure's subunits dictate its properties. The field of molecular morphogenesis has traditionally been concerned with describing these links, decoding the molecular mechanisms that give rise to the shape and structure of cells, tissues, organs, and organisms. Recent advances in synthetic biology promise unprecedented control over these molecular mechanisms; this opens the path to not just probing morphogenesis but directing it. This review explores several frontiers in the nascent field of synthetic morphogenesis, including programmable tissues and organs, synthetic biomaterials and programmable matter, and engineering complex morphogenic systems de novo. We will discuss each frontier's objectives, current approaches, constraints and challenges, and future potential. PMID- 27270297 TI - Building Spatial Synthetic Biology with Compartments, Scaffolds, and Communities. AB - Traditional views of synthetic biology often treat the cell as an unstructured container in which biological reactions proceed uniformly. In reality, the organization of biological molecules has profound effects on cellular function: not only metabolic, but also physical and mechanical. Here, we discuss a variety of perturbations available to biologists in controlling protein, nucleotide, and membrane localization. These range from simple tags, fusions, and scaffolds to heterologous expression of compartments and other structures that confer unique physical properties to cells. Next, we relate these principles to those guiding the spatial environments outside of cells such as the extracellular matrix. Finally, we discuss new directions in building intercellular organizations to create novel symbioses. PMID- 27270298 TI - Phylogenetic analysis and pathogenicity of H3 subtype avian influenza viruses isolated from live poultry markets in China. AB - H3 subtype influenza A virus is one of the main subtypes that threats both public and animal health. However, the evolution and pathogenicity of H3 avian influenza virus (AIV) circulating in domestic birds in China remain largely unclear. In this study, seven H3 AIVs (four H3N2 and three H3N8) were isolated from poultry in live poultry market (LPM) in China. Phylogenetic analyses of full genomes showed that all viruses were clustered into Eurasian lineage, except N8 genes of two H3N8 isolates fell into North American lineage. Intriguingly, the N8 gene of one H3N8 and PB2, PB1, NP and NS of two H3N2 isolates have close relationship with those of the highly pathogenic H5N8 viruses circulating in Korea and United States, suggesting that the H3-like AIV may contribute internal genes to the highly pathogenic H5N8 viruses. Phylogenetic tree of HA gene and antigenic cross reactivity results indicated that two antigenically different H3 viruses are circulating in LPM in China. Most of the H3 viruses replicated in mice lung and nasal turbinate without prior adaptation, and the representative H3 viruses infected chickens without causing clinical signs. The reassortment of H3 subtype influenza viruses warrants continuous surveillance in LPM in China. PMID- 27270299 TI - Stereotactic radiosurgery as a feasible treatment for intramedullary spinal arteriovenous malformations: a single-center observation. AB - Spinal cord intramedullary arteriovenous malformations are rare. For patients suffering from either hemorrhage or myelopathy, surgical or endovascular interventions are indicated. However, complete eradication of the nidus is often difficult because of its intramedullary location and complex angioarchitecture. In this report, we evaluate the feasibility and safety of stereotactic radiosurgery as a treatment modality for intramedullary spinal arteriovenous malformations (AVMs). Between 2010 and 2014, we performed stereotactic radiosurgery to treat four patients with intramedullary AVM and one with spinal arteriovenous metameric syndrome (one woman and four men; age range, 31-66 years). Three patients presented with myelopathy, and two suffered hemorrhages. Nidi were located in the cervical (three cases) and thoracic (two cases) spinal cord regions. Based on the angioarchitecture, surgery and endovascular embolization were indicated. When both modalities were deemed hazardous, radiosurgery using CyberKnifeTM was offered. Radiation using marginal doses of 18 Gy was administered in three fractions. The mean follow-up period was 37.2 months (range, 16-62 months). After treatment, two of the three patients with myelopathy experienced either improvement or stabilization of their symptoms and one experienced worsening of dysesthesia. In two patients with hemorrhage, symptoms improved in one and remained stable in the other. No further hemorrhagic episodes were evident during follow-up. Follow-up angiograms showed marked shrinkage of the nidus located in the thoracic spinal cord in one case and angiographic stabilization in the others. As a treatment modality for intramedullary AVMs, CyberKnifeTM is safe and can be considered when surgery or endovascular therapy is not indicated. To determine optimum radiation doses and protocols for treating spinal AVMs, further studies with more patients and long-term follow-up are required. PMID- 27270301 TI - Non-anaplastic peripheral T cell lymphoma in children and adolescents-an international review of 143 cases. AB - Peripheral T cell lymphomas (PTCL) are rare in children and adolescents, and data about outcome and treatment results are scarce. The present study is a joint, international, retrospective analysis of 143 reported cases of non-anaplastic PTCL in patients <19 years of age, with a focus on treatment and outcome features. One hundred forty-three patients, between 0.3 and 18.7 years old, diagnosed between 2000 and 2015 were included in the study. PTCL not otherwise specified was the largest subgroup, followed by extranodal NK/T cell lymphoma, hepatosplenic T cell lymphoma (HS TCL), and subcutaneous panniculitis-like T cell lymphoma (SP TCL). Probability of overall survival (pOS) at 5 years for the whole group was 0.56 +/- 0.05, and probability of event-free survival was (pEFS) 0.45 +/- 0.05. Patients with SP TCL had a good outcome with 5-year pOS of 0.78 +/- 0.1 while patients with HS TCL were reported with 5-year pOS of only 0.13 +/- 0.12. Twenty-five percent of the patients were reported to have a pre-existing condition, and this group had a dismal outcome with 5-year pOS of 0.29 +/- 0.09. The distribution of non-anaplastic PTCL subtypes in pediatric and adolescent patients differs from what is reported in adult patients. Overall outcome depends on the subtype with some doing better than others. Pre-existing conditions are frequent and associated with poor outcomes. There is a clear need for subtype based treatment recommendations for children and adolescents with PTCL. PMID- 27270302 TI - RK-144171, a new benadrostin derivative produced by Streptomyces sp. RK88-1441. PMID- 27270300 TI - SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury. AB - Ischemia reperfusion (IR) injury is harmful to skeletal muscles and causes mitochondrial oxidative stress. Pterostilbene (PTE), an analogue of resveratrol, has organic protective effects against oxidative stress. However, no studies have investigated whether PTE can protect against IR-related skeletal muscular injury. In this study, we sought to evaluate the protective effect of PTE against IR related skeletal muscle injury and to determine the mechanisms in this process. Male Sprague-Dawley rats were pretreated with PTE for a week and then underwent limb IR surgery. The IR injury induced segmental necrosis and apoptosis, myofilament disintegration, thicker interstitial spaces, and inflammatory cell infiltration. Furthermore, mitochondrial respiratory chain activity in the muscular tissue was inhibited, methane dicarboxylic aldehyde concentration and myeloperoxidase activity were up-regulated, and superoxide dismutase was down regulated after IR. However, these effects were significantly inhibited by PTE in a dose-dependent manner. The mechanism underlying IR injury is attributed to the down-regulation of silent information regulator 1 (SIRT1)-FOXO1/p53 pathway and the increase of the Bax/Bcl2 ratio, Cleaved poly ADP-ribose polymerase 1, Cleaved Caspase 3, which can be reversed with PTE. Furthermore, EX527, an SIRT1 inhibitor, counteracted the protective effects of PTE on IR-related muscle injury. In conclusion, PTE has protective properties against IR injury of the skeletal muscles. The mechanism of this protective effect depends on the activation of the SIRT1-FOXO1/p53 signaling pathway and the decrease of the apoptotic ratio in skeletal muscle cells. PMID- 27270303 TI - Impact of Staphylococcus aureus accessory gene regulator (agr) system on linezolid efficacy by profiling pharmacodynamics and RNAIII expression. PMID- 27270304 TI - Chemical and biological studies of reveromycin A. AB - The research on antibiotics requires the integration of broad areas, such as microbiology, organic chemistry, biochemistry and pharmacology. It is similar to the field of chemical biology that is recently popular as an approach for drug discovery. When we isolate a new compound from a microorganism, we can pursue the interesting research on chemistry and biology. In this review, I would like to introduce our achievements in relation to reveromycin A. PMID- 27270305 TI - Structure-property relationships of photoresponsive inhibitors of the kinesin motor. AB - Recently we demonstrated the photoregulation of the activity of kinesin-1 using an azobenzene-tethered peptide (azo-peptide: Azo-Ile-Pro-Lys-Ala-Ile-Gln-Ala-Ser His-Gly-Arg-OH). To understand the mechanism behind this photoswitchable inhibition, here we studied the structure-property relationships of a range of azo-peptides through systematic variations in the structures of the peptide and azobenzene units. The vital peptide sequence for kinesin inhibition-mediated through electrostatic, hydrophobic and C-Hpi interactions-was the same as that for the self-inhibition of kinesin. We also identified substituents on the azobenzene capable of enhancing the photoswitchability of inhibition. As a result, we developed a new inhibitor featuring a relatively short peptide unit ( Arg-Ile-Pro-Lys-Ala-Ile-Arg-OH) and an azobenzene unit bearing a para-OMe group. In the trans form of its azobenzene unit, this finely tuned inhibitor stopped the kinesin-driven gliding motility of microtubules completely at a relatively low concentration, yet allowed gliding motility with a relatively high velocity in the cis form obtained after UV irradiation. PMID- 27270307 TI - A prognostic model combining CD4/CD8 ratio and N stage predicts the risk of distant metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy. AB - This study aimed to evaluate the correlation between circulating lymphocyte subsets and clinical variables, and design an effective prognostic model for distant metastasis-free survival (DMFS) in NPC. In this study, subsets of circulating lymphocytes were determined in 719 non-metastatic NPC patients before treatment. Overall survival and DMFS was monitored. Significant prognostic factors were identified using univariate and multivariate analyses. Results showed that the percentage of CD19+ lymphocytes correlated negatively with TNM stage (r = -0.082, P = 0.028). Patients with higher CD4/CD8 ratios (>= 1.77) showed better 5-year DMFS than patients with lower ratios (91.9% vs. 85.4%, P < 0.001). Multivariate analysis revealed that CD4/CD8 ratio (HR, 0.450; 95% confidence interval [CI], 0.266-0.760; P = 0.003) and N classification (HR, 2.294; 95% CI, 1.370-3.839; P = 0.002) were independently prognostic factors for DMFS. The prognostic N-R model was developed and divided patients into three groups: (1) low-risk (early N stage and CD4/CD8 ratio >= 1.77); (2) intermediate risk (advanced N stage or CD4/CD8 ratio < 1.77) and (3) high-risk (advanced N stage and CD4/CD8 ratio < 1.77) of distant metastasis. In conclusion our prognostic model, based on clinical N stage and CD4/CD8 ratio, may predict the risk of distant metastasis, allowing individualized treatment for NPC. PMID- 27270306 TI - Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection. AB - Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells-with T-cell help-undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge. PMID- 27270308 TI - IRE1alpha inhibition by natural compound genipin on tumour associated macrophages reduces growth of hepatocellular carcinoma. AB - Accumulating evidences postulated the influential roles of macrophages in mediating hepatocellular carcinoma (HCC) initiation and progression. In this study, we demonstrate that a small molecule, genipin reduced HCC growth through suppressing IRE1alpha-mediated infiltration and priming of tumour associated macrophages (TAMs). Oral administration of genipin (30mg/kg/2days) suppressed orthotopic HCC tumour growth without challenging the viability and proliferation of HCC cells. Genipin reduced infiltration of inflammatory monocytes into liver and tumour thereby suppressed TAMs presence in HCC microenvironment. Suppression of HCC growth was diminished in HCC-implanted mice with depletion of TAMs by liposome clodronate. Genipin inhibited the TAMs migration, and reduced expression of TAMs-derived inflammatory cytokines that favors HCC proliferation. This is revealed by the in vivo deletion of IRE1alpha on TAMs in genipin-treated HCC implanted mice. Diminishing IRE1alpha neutralised the inhibitory effect of genipin on TAMs. Silencing the expression of IRE1alpha greatly reduced TAMs migration and expression of inflammatory cytokines that prime HCC proliferation. Suppression of IRE1alpha led to reduced XBP-1 splicing and NF-kappaB activation. The reduced association of IRE1alpha with TRAF2 and IKK complex may be responsible for the genipin-mediated inactivation of NF-kappaB. The findings show the important role of TAMs in inhibitory effect of genipin on HCC, and TAMs expressing IRE1alpha as a promising target for disrupting the tumour environment that favor of HCC development. PMID- 27270309 TI - Aberrant methylation-mediated silencing of microRNAs contributes to HPV-induced anchorage independence. AB - Cervical cancer and a subset of anogenital and head-and-neck carcinomas are caused by high-risk types of the human papillomavirus (hrHPV). During hrHPV induced malignant transformation keratinocytes become able to grow anchorage independently, a tumorigenic trait at least partly associated with inactivation of tumor suppressor genes. We used hrHPV-containing keratinocytes to investigate the role of DNA methylation-mediated silencing of microRNAs (miRNAs) in the acquisition of anchorage independence.Anchorage dependent (n=11) and independent passages (n=19) of 4 hrHPV-immortalized keratinocyte cell lines were treated with 2'-deoxy-5-azacytidine (DAC). Genome-wide miRNA expression profiles before and after treatment were compared to identify miRNAs silenced by methylation. Bisulfite sequencing and methylation-specific PCR showed increased methylation of hsa-mir-129-2/-137/-935/-3663/-3665 and -4281 in anchorage independent HPV transformed keratinocytes and cervical cancer cell lines. Mature miRNAs derived from hsa-mir-129-2/-137/-3663 and -3665 showed functional relevance as they decreased anchorage independence in cervical cancer cell lines. Cervical (pre)cancerous lesions demonstrated increased methylation of hsa-mir-129-2/-935/ 3663/-3665 and -4281, underlining the clinical relevance of our findings.In conclusion, methylation-mediated silencing of tumor suppressive miRNAs contributes to acquisition of an anchorage independent phenotype. This study further substantiates the importance of miRNAs during early stages of carcinogenesis and underlines their potential as both disease markers and therapeutic targets. PMID- 27270310 TI - Long noncoding RNA RP11-838N2.4 enhances the cytotoxic effects of temozolomide by inhibiting the functions of miR-10a in glioblastoma cell lines. AB - Resistance to temolozomide (TMZ), the standard chemotherapy agent for treating glioblastomas (GBM), is a major clinical problem for patients with GBM. Recently, long noncoding RNAs (lncRNAs) have been implicated in chemotherapy resistance in various cancers. In this study, we found that the level of the lncRNA RP11 838N2.4 was lower in TMZ-resistant GBM cells (U87TR, U251TR) compared to the parental, non-resistant GBM cells (U87, U251). In GBM patients, the decreased level of lncRNA RP11-838N2.4 correlated with higher risk of GBM relapse, as well as shorter postoperative survival times. We further found that lncRNA RP11 838N2.4 could enhances the cytotoxic effects of temozolomide to GBM cells both in vivo and in vitro. Moreover, lncRNA RP11-838N2.4 acts as an endogenous sponge, suppressing the function of miR-10a through conserved sequences and increasing the expression of EphA8 that enhanced the rate of cell apoptosis, thereby intensified sensitivity of GBM cells to TMZ. Additionally, lncRNA RP11-838N2.4 inhibited the activity of transforming growth factor-beta (TGF-beta) independent of miR-10a. Finally, Characterization of lncRNA RP11-838N2.4 could contribute to strategies for enhancing the efficacy of TMZ. PMID- 27270311 TI - Direct contact with perivascular tumor cells enhances integrin alphavbeta3 signaling and migration of endothelial cells. AB - The secretion of soluble pro-angiogenic factors by tumor cells and stromal cells in the perivascular niche promotes the aggressive angiogenesis that is typical of glioblastoma (GBM). Here, we show that angiogenesis also can be promoted by a direct interaction between brain tumor cells, including tumor cells with cancer stem-like properties (CSCs), and endothelial cells (ECs). As shown in vitro, this direct interaction is mediated by binding of integrin alphavbeta3 expressed on ECs to the RGD-peptide in L1CAM expressed on CSCs. It promotes both EC network formation and enhances directed migration toward basic fibroblast growth factor. Activation of alphavbeta3 and bone marrow tyrosine kinase on chromosome X (BMX) is required for migration stimulated by direct binding but not for migration stimulated by soluble factors. RGD-peptide treatment of mice with established intracerebral GBM xenografts significantly reduced the percentage of Sox2 positive tumor cells and CSCs in close proximity to ECs, decreased integrin alphavbeta3 and BMX activation and p130CAS phosphorylation in the ECs, and reduced the vessel surface area. These results reveal a previously unrecognized aspect of the regulation of angiogenesis in GBM that can impact therapeutic anti angiogenic targeting. PMID- 27270312 TI - Quantitative proteomics reveals that distant recurrence-associated protein R-Ras and Transgelin predict post-surgical survival in patients with Stage III colorectal cancer. AB - Surgical resection supplemented with adjuvant chemotherapy is the current preferred treatment for Stage III colorectal cancer (CRC). However, as many as 48% of patients who undergo curative resection eventually suffer from incurable distant recurrence. To investigate the molecular mechanisms involved in Stage III CRC post-surgical distant recurrence, we identified a total of 146 differentially expressed proteins (DEPs) associated with distant recurrence in Stage III CRC using TMT-based quantitative mass spectrometry. Among these DEPs, the altered expressions of R-Ras and Transgelin were then validated in 192 individual specimens using immunohistochemistry (IHC). Furthermore, Kaplan-Meier analysis revealed that the levels of R-Ras and Transgelin were significantly associated with 5-year overall survival (OS) and disease-free survival (DFS), and multivariate Cox-regression analyses revealed that R-Ras and Transgelin were independent prognostic factors for OS and DFS, respectively. In conclusion, this study identified potential biochemical players involved in distant recurrence and indicates that R-Ras and Transgelin are potential post-surgical prognostic biomarkers for Stage III CRC. This proteomics data have been submitted to Proteome Xchange under accession number PXD002903. PMID- 27270313 TI - The impact of intermittent versus continuous exposure to EGFR tyrosine kinase inhibitor on selection of EGFR T790M-mutant drug-resistant clones in a lung cancer cell line carrying activating EGFR mutation. AB - Drug-resistant cell lines are essential tools for investigating the mechanisms of resistance to molecular-targeted anti-cancer drugs. However, little is known about how to establish clinically relevant drug-resistant cell lines. Our study examined the impact of a drug-free period on the establishment of a cell line with clinically relevant resistance to molecular-targeted drugs. We used PC9 cells, a lung cancer cell line carrying EGFR mutation, because this is a validated target for EGFR tyrosine kinase inhibitors (TKI). PC9 cells were intermittently or continuously exposed to increasing concentrations of gefitinib (0.01 MUM to 1.0 MUM) and the emergence of the most common acquired resistance mutation in EGFR, T790M, was determined. T790M was detected at a 25-fold lower drug concentration in cells continuously exposed to gefitinib (PC9/GRc) than in cells intermittently exposed to gefitinib (PC9/GRi) (0.04 MUM vs 1.0 MUM, respectively). The mutation frequencies at those drug concentrations were 19.8% and 8.0% in PC9/GRc and PC9/GRi cells, respectively. After drug-free culture for 8 weeks, resistance to gefitinib decreased in the PC9/GRi cells but not in the PC9/GRc cells. In the PC9/GRc cells, the frequency of the T790M mutation was consistently about 20% from 0.04 MUM to 1.0 MUM of gefitinib. In the PC9/GRc cells, the T790M mutation was detected in all single-cell clones, at frequencies ranging from 7.0% to 37.0%, with a median of 19.5% (95% confidence interval, 17.3%-20.9%). In conclusion, compared with intermittent drug exposure, continuous exposure might select better minor drug-resistant clones when creating cell lines resistant to molecular-targeted drugs. PMID- 27270314 TI - Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: A preliminary study. AB - Peritoneal metastasis occurs in more than half of patients with unresectable or recurrent gastric cancer and is associated with the worst prognosis. The associated genomic events and pathogenesis remain ambiguous. The aim of the present study was to characterize the mutation spectrum of gastric cancer with peritoneal metastasis and provide a basis for the identification of new biomarkers and treatment targets. Matched pairs of normal gastric mucosa and peritoneal tissue and matched pairs of primary tumor and peritoneal metastasis were collected from one patient for whole-exome sequencing (WES); Sanger sequencing was employed to confirm the somatic mutations. G>A and C>T mutations were the two most frequent transversions among the somatic mutations. We confirmed 48somatic mutations in the primary site and 49 in the peritoneal site. Additionally, 25 non-synonymous somatic variations (single-nucleotide variants, SNVs) and 2 somatic insertions/deletions (INDELs) were confirmed in the primary tumor, and 30 SNVs and 5 INDELs were verified in the peritoneal metastasis. Approximately 59% of the somatic mutations were shared between the primary and metastatic site. Five genes (TP53, BAI1, THSD1, ARID2, and KIAA2022) verified in our study were also mutated at a frequency greater than 5%in the COSMIC database. We also identified 9genes (ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16, and NCAM1) that were only mutated in metastasis and are expected to become treatment targets. In conclusion, we observed that the majority of the somatic mutations in the primary site persisted in metastasis, whereas several single nucleotide polymorphisms occurred de novo at the second site. PMID- 27270315 TI - Characteristics of human papillomaviruses infection in men with genital warts in Shanghai. AB - Human papillomaviruses (HPV) infected men causes continued transmission of HPV to women. The prevalence of 15 high-risk HPV strains (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68) and 6 low-risk HPV strains (HPV6, 11, 42, 43, 44 and CP8304) were evaluated in 935 males with genital warts. Of the 447 (447/935, 47.8%) HPV DNA positive subjects, 230 (24.6%), 356 (38.1%) and 139 (14.9%) were infected by high-risk, low-risk and both high and low-risk HPV respectively. Of the 356 low-risk HPV infected subjects, 333(93.5%) were infected by single HPV strain; 203 (57.0%), 147 (41.3%), 24 (6.7%) and 5 (1.4%) were infected with HPV genotype 6, 11, CP8304 and 44 respectively; population with age <= 20 showed the highest infection rate. High-risk HPV are also highly prevalent in our patients, genotype 16, 58, 51, 39, 52 and 53 are the top five prevalent genotypes with infection rates of 27.4%, 18.7%, 14.3%, 13.9%, 12.6% and 12.6% respectively; only 68.3% subjects were sole infection; subjects with 41 <= age <= 50 showed the highest infection rate. Both high and low-risk HPV are highly prevalent in men with genital warts, its impact on women HPV control and prevention need further evaluation. PMID- 27270316 TI - 14,15-EET induces the infiltration and tumor-promoting function of neutrophils to trigger the growth of minimal dormant metastases. AB - Infiltrating neutrophils are known to promote in the development of tumor. However, it is unclear whether and how neutrophils are involved in triggering the growth of dormant metastases. Here we show that 14,15-epoxyeicosatrienoic acid (14,15-EET) can trigger the growth of dormant micrometastases by inducing neutrophilic infiltration and converting neutrophil function. 14,15-EET triggered neutrophil infiltration in metastatic lesions by activating STAT3 and JNK pathways to induce the expression of human IL-8 and murine CXCL15 in corresponding tumor cells. The continuous expression of hIL-8/mCXCL15 was maintained by the sustained and enhanced activation of JNK pathway. 14,15-EET up regulated miR-155 expression by activating STAT3 and JNK pathways. miR-155 in turn down-regulated the expression of SHIP1 and DET1, thus augmenting the activation of JNK and c-Jun. Moreover, the function of neutrophils was converted from tumor-suppressing to tumor-promoting by 14,15-EET in vivo. By inducing the production of G-CSF/IL-6 in vivo, 14,15-EET induced the enhancement of STAT3 activation in neutrophils to increase MMP-9 expression and decrease TRAIL expression. Neutrophil-derived MMP-9 was required for 14,15-EET to induce angiogenesis during the growth of dormant micrometastases. Depleting neutrophils or inhibiting hIL-8/mCXCL15 up-regulation resulted in the failure of 14,15-EET to promote the development of micrometastases. These findings reveal a mechanism through which the infiltration and tumor-promoting function of neutrophils could be induced to trigger the growth of dormant metastases, which might be a driving force for the tumor recurrence based on dormant metastases. PMID- 27270317 TI - NEAT1 upregulates EGCG-induced CTR1 to enhance cisplatin sensitivity in lung cancer cells. AB - Platinum-based drugs are the firstline of treatment for non-small cell lung cancer (NSCLC), but resistance to these drugs is a major obstacle to effective chemotherapy. Our previous study revealed that the green tea polyphenol, EGCG, induced cisplatin transporter CTR1 (copper transporter 1) and enhanced cisplatin sensitivity in ovarian cancer. In this study, we found that EGCG upregulated CTR1 and increased platinum accumulation in NSCLC (A549, H460 and H1299) cells, cDDP resistant A549 cells and a nude mouse xenograft model. Cisplatin-induced inhibition of cell growth was enhanced by EGCG treatment in vitro and in vivo. MicroRNA hsa-mir-98-5p appears to suppress CTR1 gene expression, while long non coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) appears to enhance it. Bioinformatics analysis showed that hsa-mir-98-5p has specific complementary binding sites for NEAT1. In addition, hsa-mir-98-5p was predicted to be a putative CTR1 target. NEAT1 may act as a competing endogenous lncRNA to upregulate EGCG-induced CTR1 by sponging hsa-mir-98-5p in NSCLC. Our findings reveal a novel mechanism how NEAT1 upregulates EGCG-induced CTR1 and enhances cisplatin sensitivity in vitro and in vivo, and suggest EGCG could serve as an effective adjuvant chemotherapeutic in lung cancer treatment. PMID- 27270318 TI - Anti-tax interacting protein-1 (TIP-1) monoclonal antibody targets human cancers. AB - Radiation-inducible neo-antigens are proteins expressed on cancer cell surface after exposure to ionizing radiation (IR). These neo-antigens provide opportunities to specifically target cancers while sparing normal tissues. Tax interacting protein-1 (TIP-1) is induced by irradiation and is translocated to the surface of cancer cells. We have developed a monoclonal antibody, 2C6F3, against TIP-1.Epitope mapping revealed that 2C6F3 binds to the QPVTAVVQRV epitope of the TIP-1 protein. 2C6F3 binds to the surface of lung cancer (A549, LLC) and glioma (D54, GL261) cell lines. 2C6F3 binds specifically to TIP-1 and ELISA analysis showed that unconjugated 2C6F3 efficiently blocked binding of radiolabeled 2C6F3 to purified TIP-1 protein. To study in vivo tumor binding, we injected near infrared (NIR) fluorochrome-conjugated 2C6F3 via tail vein in mice bearing subcutaneous LLC and GL261 heterotopic tumors. The NIR images indicated that 2C6F3 bound specifically to irradiated LLC and GL261 tumors, with little or no binding in un-irradiated tumors.We also determined the specificity of 2C6F3 to bind tumors in vivo using SPECT/CT imaging. 2C6F3 was conjugated with diethylene triamine penta acetic acid (DTPA) chelator and radiolabeled with 111Indium (111In). SPECT/CT imaging revealed that 111In-2C6F3 bound more to the irradiated LLC tumors compared to un-irradiated tumors. Furthermore, injection of DTPA-2C6F3 labeled with the therapeutic radioisotope, 90Y, (90Y-DTPA-2C6F3) significantly delayed LLC tumor growth. 2C6F3 mediated antibody dependent cell-mediated cytotoxicity (ADCC) and antibody dependent cell-mediated phagocytosis (ADCP) in vitro.In conclusion, the monoclonal antibody 2C6F3 binds specifically to TIP-1 on cancer and radio-immunoconjugated 2C6F3 improves tumor control. PMID- 27270319 TI - E-cadherin re-expression shows in vivo evidence for mesenchymal to epithelial transition in clonal metastatic breast tumor cells. AB - Substantial experimental evidence has shown that dedifferentiation from an epithelial state to a mesenchymal-like state (EMT) drives tumor cell metastasis. This transition facilitates tumor cells to acquire motility and invasive features. Intriguingly, tumor cells at the metastatic site are primarily epithelial, and it is believed that they differentiate back to an epithelial state by a process called mesenchymal to epithelial transition (MET). However, there is little in vivo evidence to support the MET process. To investigate EMT and MET in vivo, we generated two epithelial (E) and two mesenchymal (M) primary clonal cell lines from a spontaneous mouse mammary tumor (Tg MMTV/neu). These cells were labeled with reporters (GFP and luciferase), and tracked in vivo during primary tumor growth and subsequent secondary metastasis. Once E cells were implanted into the mammary fat pad, E-cadherin expression progressively decreased and continued to decrease as the primary tumor enlarged over time. A greater percentage of E tumor cells expressed E-cadherin at the secondary metastatic site as compared to the corresponding primary tumor site. Collectively, these data provide direct in vivo evidence that epithelial tumor cells have metastatic potential, undergo EMT at the primary tumor site, and MET at the metastatic site. PMID- 27270320 TI - PIK3C2A mRNA functions as a miR-124 sponge to facilitate CD151 expression and enhance malignancy of hepatocellular carcinoma cells. AB - Competing endogenous RNAs (ceRNAs) are RNA transcripts that can crosstalk with each other by competing for shared microRNAs (miRNAs) through miRNA response elements (MREs). Involved in ceRNA networks, the RNA transcripts may be in a balance, disruption of which could lead to tumorigenesis. Here we reveal a ceRNA interaction between PIK3C2A and CD151 mRNAs in hepatocellular carcinoma (HCC) cells. PIK3C2A is a candidate ceRNA of CD151 because mRNA 3' untranslated regions (3'UTRs) of these two genes contain miR-124 binding sites. miR-124 is downregulated, while PIK3C2A and CD151 are upregulated in HCC cells compared with normal hepatocytes. Direct and negative regulation of PIK3C2A and CD151 by miR 124 was confirmed in HCC cells. miR-124 and the two potential ceRNAs are all recruited to the RNA-induced silencing complex (RISC). In HCC cell lines QGY- 7703 and SMMC-7721, and normal hepatic cell line HL-7702, miR-124 plays a tumor suppressor role by targeting PIK3C2A and CD151. The MREs within PIK3C2A 3'UTR can independently stimulate CD151 expression level by acting as miR-124 decoys. PIK3C2A MREs enhance HCC cell malignancy by absorbing endogenous miR-124 and activating CD151 in HCC cells. We conclude that PIK3C2A 3'UTR functions as a trans activator to stimulate CD151 by competing for miR-124 binding in HCC cells. The collaboration of PIK3C2A and CD151 through ceRNA mechanism may be implicated in HCC initiation and development. PMID- 27270321 TI - Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia. AB - Sirt3, a mitochondrial deacetylase, participates in the regulation of multiple cellular processes through its effect on protein acetylation. The objective of this study was to explore the role of Sirt3 in the mitochondrial autophagy (mitophagy), a process of the specific autophagic elimination of damaged mitochondria. We found that silencing of Sirt3 expression in human glioma cells by RNA interference blunted the hypoxia-induced the localization of LC3 on the mitochondria, and the degradation of mitochondria. These results suggest an important involvement of this protein deacetylase in the induction of mitophagy in cancer cells subjected to hypoxia. Further, we demonstrated that Sirt3 activated the hypoxia-induced mitophagy by increasing the interaction of VDAC1 with Parkin. In the cells subjected to hypoxia, inhibition of Sirt3-mediated mitophagy further decreased the mitochondrial membrane potential, and increased the accumulation of ROS that triggers the degradation of anti-apoptotic proteins Mcl-1 and survivin through the proteasomal pathway. Silencing of Sirt3 expression also promoted apoptosis, and enhanced the sensitivity of cancer cells to hypoxia. The regulatory role of Sirt3 in autophagy and apoptosis was also observed in human breast cancer cells. The results of the current study reveal Sirt3 as a novel regulator coupling mitophagy and apoptosis, two important cellular processes that determine cellular survival and death. PMID- 27270322 TI - KCNN4 and S100A14 act as predictors of recurrence in optimally debulked patients with serous ovarian cancer. AB - Approximately 50-75% of patients with serous ovarian carcinoma (SOC) experience recurrence within 18 months after first-line treatment. Current clinical indicators are inadequate for predicting the risk of recurrence. In this study, we used 7 publicly available microarray datasets to identify gene signatures related to recurrence in optimally debulked SOC patients, and validated their expressions in an independent clinic cohort of 127 patients using immunohistochemistry (IHC). We identified a two-gene signature including KCNN4 and S100A14 which was related to recurrence in optimally debulked SOC patients. Their mRNA expression levels were positively correlated and regulated by DNA copy number alterations (CNA) (KCNN4: p=1.918e-05) and DNA promotermethylation (KCNN4: p=0.0179; S100A14: p=2.787e-13). Recurrence prediction models built in the TCGA dataset based on KCNN4 and S100A14 individually and in combination showed good prediction performance in the other 6 datasets (AUC:0.5442-0.9524). The independent cohort supported the expression difference between SOC recurrences. Also, a KCNN4 and S100A14-centered protein interaction subnetwork was built from the STRING database, and the shortest regulation path between them, called the KCNN4-UBA52-KLF4-S100A14 axis, was identified. This discovery might facilitate individualized treatment of SOC. PMID- 27270323 TI - Ellagitannin-rich cloudberry inhibits hepatocyte growth factor induced cell migration and phosphatidylinositol 3-kinase/AKT activation in colon carcinoma cells and tumors in Min mice. AB - Berries have been found to inhibit colon carcinogenesis in animal models, and thus represent a potential source of compounds for prevention and treatment of colorectal cancer. The mechanistic basis for their effects is not well understood. We used human colon carcinoma cells and Min mice to investigate the effects of ellagitannin-rich cloudberry (Rubus chamaemorus) extract on cancer cell migration and underlying cell signaling. Intrinsic and hepatocyte growth factor (HGF) -induced cell motility in human HT29 and HCA7 colon carcinoma cells was assessed carrying out cell scattering and scratch wound healing assays using time-lapse microscopy. Activation of Met, AKT, and ERK in cell lines and tumors of cloudberry-fed Min mice were determined using immunoprecipitation, Western blot and immunohistochemical analyses. Cloudberry extract significantly inhibited particularly HGF-induced cancer cell migration in both cell lines. Cloudberry extract inhibited the Met receptor tyrosine phosphorylation by HGF and strongly suppressed HGF-induced AKT and ERK activation in both HT29 and HCA7 cells. Consistently, cloudberry feeding (10% w/w freeze-dried berries in diet for 10 weeks) reduced the level of active AKT and prevented phosphoMet localization at the edges in tumors of Min mice. These results indicate that cloudberry reduces tumor growth and cancer cell motility by inhibiting Met signaling and consequent activation of phosphatidylinositol 3-kinase/AKT in vitro and in tumors in vivo. As the Met receptor is recognized to be a major target in cancer treatment, our results suggest that dietary phytochemicals may have therapeutic value in reducing cancer progression and metastasis. PMID- 27270324 TI - Eukaryotic translation initiation factor 3B accelerates the progression of esophageal squamous cell carcinoma by activating beta-catenin signaling pathway. AB - INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors. Eukaryotic translation initiation factors 3B (EIF3B) is considered to influence tumor proliferation, invasion, apoptosis and cell cycle, which act together to promote the progression of tumors. However, the role of EIF3B in ESCC is unknown. This study aims to explore the clinical and biological role of EIF3B in ESCC. RESULTS: EIF3B expressions were up-regulated in both ESCC tissues and cell lines. Overexpression of EIF3B was associated with tumor depth, lymph node metastasis and advanced TNM stage. Importantly, patients with high EIF3B expression suffered shorter overall and disease-free survival. Knockdown of EIF3B could inhibit cell proliferation and invasion, promote cell apoptosis, and interfere the cell cycle in vitro. EIF3B-knockdown cells could form smaller subcutaneous tumors in vivo. Finally, we demonstrated EIF3B could activate beta-catenin signaling pathway. METHODS: Immunohistochemical staining and Western blot were performed to detect the EIF3B expression in ESCC patient tissues and cell lines. The association between EIF3B expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Then, CCK-8, colony formation, Transwell and wound-healing assay were performed to compare the bio functional change after knockdown of EIF3B. Flow cytometry was applied to analyze the change of cell apoptosis and cycle induced by EIF3B knockdown. Tumor xenograft assay was done to verify the in-vitro results. CONCLUSIONS: EIF3B might serve as a novel marker for predicting prognosis of ESCC patients and as a potential therapeutic target, individually or together with other subunits of EIF3 complex. PMID- 27270325 TI - Cell-free DNA mutations as biomarkers in breast cancer patients receiving tamoxifen. AB - The aim was to identify mutations in serum cell-free DNA (cfDNA) associated with disease progression on tamoxifen treatment in metastatic breast cancer (MBC). Sera available at start of therapy, during therapy and at disease progression were selected from 10 estrogen receptor (ER)-positive breast cancer patients. DNA from primary tumor and normal tissue and cfDNA from minute amounts of sera were analyzed by targeted next generation sequencing (NGS) of 45 genes (1,242 exons). At disease progression, stop-gain single nucleotide variants (SNVs) for CREBBP (1 patient) and SMAD4 (1 patient) and non-synonymous SNVs for AKAP9 (1 patient), PIK3CA (2 patients) and TP53 (2 patients) were found. Mutations in CREBBP and SMAD4 have only been occasionally reported in breast cancer. All mutations, except for AKAP9, were also present in the primary tumor but not detected in all blood specimens preceding progression. More sensitive detection by deeper re sequencing and digital PCR confirmed the occurrence of circulating tumor DNA (ctDNA) and these biomarkers in blood specimens. PMID- 27270326 TI - Loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CDC28 protein kinase regulatory subunit 1B. AB - Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients' survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B . Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC. PMID- 27270329 TI - Margaret McCartney: Bring high street pharmacists into the NHS. PMID- 27270327 TI - Tetraspanin-8 promotes hepatocellular carcinoma metastasis by increasing ADAM12m expression. AB - Recent evidence indicates that tetraspanin-8 (TSPAN8) promotes tumor progression and metastasis. In this study, we explored the effects of TSPAN8 and the molecular mechanisms underlying hepatocellular carcinoma (HCC) metastasis using various HCC cell lines, tissues from 149 HCC patients, and animal models of HCC progression. We showed that elevated expression of TSPAN8 promoted HCC invasion in vitro and metastasis in vivo, but did not influence HCC cell proliferation in vitro. Increased TSPAN8 expression in human HCC was predictive of poor survival, and multivariate analyses indicated TSPAN8 expression to be an independent predictor for both postoperative overall survival and relapse-free survival. Importantly, TSPAN8 enhanced HCC invasion and metastasis by increasing ADAM12m expression. We therefore conclude that TSPAN8 and ADAM12m may be useful therapeutic targets for the prevention of HCC progression and metastasis. PMID- 27270328 TI - MC1R is dispensable for the proteinuria reducing and glomerular protective effect of melanocortin therapy. AB - Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of [Nle(4), D-Phe(7)]-alpha-melanocyte stimulating hormone (NDP MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms. PMID- 27270330 TI - The C-terminal region of Trypanosoma cruzi MASPs is antigenic and secreted via exovesicles. AB - Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and emerging tropical disease, endemic to South America and present in non-endemic regions due to human migration. The MASP multigene family is specific to T. cruzi, accounting for 6% of the parasite's genome and plays a key role in immune evasion. A common feature of MASPs is the presence of two conserved regions: an N terminal region codifying for signal peptide and a C-terminal (C-term) region, which potentially acts as GPI-addition signal peptide. Our aim was the analysis of the presence of an immune response against the MASP C-term region. We found that this region is highly conserved, released via exovesicles (EVs) and has an associated immune response as revealed by epitope affinity mapping, IFA and inhibition of the complement lysis assays. We also demonstrate the presence of a fast IgM response in Balb/c mice infected with T. cruzi. Our results reveal the presence of non-canonical secreted peptides in EVs, which can subsequently be exposed to the immune system with a potential role in evading immune system targets in the parasite. PMID- 27270331 TI - Spatio-temporal morphology changes in and quenching effects on the 2D spreading dynamics of cell colonies in both plain and methylcellulose-containing culture media. AB - To deal with complex systems, microscopic and global approaches become of particular interest. Our previous results from the dynamics of large cell colonies indicated that their 2D front roughness dynamics is compatible with the standard Kardar-Parisi-Zhang (KPZ) or the quenched KPZ equations either in plain or methylcellulose (MC)-containing gel culture media, respectively. In both cases, the influence of a non-uniform distribution of the colony constituents was significant. These results encouraged us to investigate the overall dynamics of those systems considering the morphology and size, the duplication rate, and the motility of single cells. For this purpose, colonies with different cell populations (N) exhibiting quasi-circular and quasi-linear growth fronts in plain and MC-containing culture media are investigated. For small N, the average radial front velocity and its change with time depend on MC concentration. MC in the medium interferes with cell mitosis, contributes to the local enlargement of cells, and increases the distribution of spatio-temporal cell density heterogeneities. Colony spreading in MC-containing media proceeds under two main quenching effects, I and II; the former mainly depending on the culture medium composition and structure and the latter caused by the distribution of enlarged local cell domains. For large N, colony spreading occurs at constant velocity. The characteristics of cell motility, assessed by measuring their trajectories and the corresponding velocity field, reflect the effect of enlarged, slow-moving cells and the structure of the medium. Local average cell size distribution and individual cell motility data from plain and MC-containing media are qualitatively consistent with the predictions of both the extended cellular Potts models and the observed transition of the front roughness dynamics from a standard KPZ to a quenched KPZ. In this case, quenching effects I and II cooperate and give rise to the quenched-KPZ equation. Seemingly, these results show a possible way of linking the cellular Potts models and the 2D colony front roughness dynamics. PMID- 27270332 TI - Expression and inactivation of osteopontin-degrading PHEX enzyme in squamous cell carcinoma. AB - Proteolytic enzymes mediate the activation or inactivation of many physiologic and pathologic processes. The PHEX gene (Phosphate-regulating gene with homologies to endopeptidase on the X chromosome) encodes a metallopeptidase, which is mutated in patients with a prevalent form (1:20,000) of inherited rickets-X-linked hypophosphatemia (XLH). XLH shows growth retardation, hypophosphatemia, osteomalacia, and defective renal phosphate reabsorption and metabolism of vitamin D. Most PHEX studies have focused on bone, and recently we identified osteopontin (OPN) as the first protein substrate for PHEX, demonstrating in the murine model of XLH (Hyp mice) an increase in OPN that contributes to the osteomalacia. Besides its role in bone mineralization, OPN is expressed in many tissues, and therein has different functions. In tumor biology, OPN is known to be associated with metastasis. Here, we extend our PHEX-OPN studies to investigate PHEX expression in a squamous cell carcinoma (SCC) cell line and its possible involvement in modulating OPN function. Real-time PCR showed PHEX-OPN co-expression in SCC cells, with sequencing of the 22 exons showing no mutation of the PHEX gene. Although recombinant PHEX hydrolyze SCC-OPN fragments, unlike in bone cells, SCC-PHEX protein was not predominantly at the plasma membrane. Enzymatic activity assays, FACs and immunoblotting analyses demonstrated that membrane PHEX is degraded by cysteine proteases and the decreased PHEX activity could contribute to inappropriate OPN regulation. These results highlight for the first time PHEX in tumor biology. PMID- 27270333 TI - Dimer conformation of soluble PECAM-1, an endothelial marker. AB - Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a cell surface receptor widely distributed on endothelium and hematopoietic-derived cells, and maintain the integrity of the blood vessels. PECAM-1 is widely recognized as an endothelial cell marker. The homophilic interaction through its extracellular domain of PECAM-1 (soluble PECAM-1, or sPECAM-1) is important to its functions. However, structural details for such dimerization are not fully understood. Here we report the production of recombinant sPECAM-1 in large quantity by Drosophila expression system and the small-angle X-ray diffraction (SAXS) study. The recombinant sPECAM-1 was found to form one population of dimer, but not oligomer, and was able to bind to heparin immobilized on a chip in surface plasmon resonance imaging (SPRi) binding experiments. The results of SAXS demonstrated that sPECAM-1 formed a symmetric homodimer of Omega-shape in solution, and each protomer adopted an extended conformation. The dimer is mediated through the intermolecular interactions through the first N-terminal domain (D1) of sPECAM-1. This model provides new structural information for its homophilic interaction mechanism. PMID- 27270334 TI - Detachment of secondary dendrite arm in a directionally solidified Sn-Ni peritectic alloy under deceleration growth condition. AB - In order to better understand the detachment mechanism of secondary dendrite arm during peritectic solidification, the detachment of secondary dendrite arm from the primary dendrite arms in directionally solidified Sn-36at.%Ni peritectic alloys is investigated at different deceleration rates. Extensive detachment of secondary dendrite arms from primary stem is observed below peritectic reaction temperature TP. And an analytical model is established to characterize the detachment process in terms of the secondary dendrite arm spacing lambda2, the root radius of detached arms and the specific surface area (SV) of dendrites. It is found that the detachment mechanism is caused by not only curvature difference between the tips and roots of secondary branches, but also that between the thicker secondary branches and the thinner ones. Besides, this detachment process is significantly accelerated by the temperature gradient zone melting (TGZM) effect during peritectic solidification. It is demonstrated that the reaction constant (f) which is used to characterize the kinetics of peritectic reaction is crucial for the determination of the detachment process. The value of f not only changes with growth rate but also with solidification time at a given deceleration rate. In conclusion, these findings help the better understanding of the detachment mechanism. PMID- 27270335 TI - Phytochromes: More Than Meets the Eye. AB - Phytochromes play a key role in the regulation of plant growth and development. Phytochrome-related proteins also occur in some bacteria, fungi, and algae. We highlight recent findings on the evolution of phytochromes and discuss novel hypotheses on the function of phytochromes in diatoms, a group of mainly pelagic algae. PMID- 27270336 TI - The Yin-Yang of Cytokinin Homeostasis and Drought Acclimation/Adaptation. AB - Increasing evidence has shown that cytokinins (CKs) regulate plant drought acclimation/adaptation through a multistep phosphorelay pathway. Recent progress has allowed us to suggest a yin-and-yang-type relationship between CK homeostasis and acclimation/adaptation responses that modulates plant fitness and yields stability under drought through a complex network involving crosstalk with abscisic acid (ABA). PMID- 27270337 TI - Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma. AB - Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID- 27270338 TI - Regeneration of rat corpora cavernosa tissue by transplantation of CD133+ cells derived from human bone marrow and placement of biodegradable gel sponge sheet. AB - The objective is to develop an easier technique for regenerating corpora cavernosa tissue through transplantation of human bone marrow-derived CD133 + cells into a rat corpora cavernosa defect model. We excised 2 mm * 2 mm squares of the right corpora cavernosa of twenty-three 8-week-old male nude rats. Alginate gel sponge sheets supplemented with 1 * 10 4 CD133 + cells were then placed over the excised area of nine rats. Functional and histological evaluations were carried out 8 weeks later. The mean intracavernous pressure/mean arterial pressure ratio for the nine rats (0.34258 +/- 0.0831) was significantly higher than that for eight rats with only the excision (0.0580 +/- 0.0831, P = 0.0238) and similar to that for five rats for which the penis was exposed, and there was no excision (0.37228 +/- 0.1051, P = 0.8266). Immunohistochemical analysis revealed that the nine fully treated rats had venous sinus-like structures and quantitative reverse transcription polymerase chain reaction analysis of extracts from their alginate gel sponge sheets revealed that the amounts of mRNA encoding the nerve growth factor (NGF), and vascular endothelial growth factor (VEGF) were significantly higher than those for rats treated with alginate gel sheets without cell supplementation (NGF: P = 0.0309; VEGF: P < 0.0001). These findings show that transplantation of CD133 + cells accelerates functional and histological recovery in the corpora cavernosa defect model. PMID- 27270339 TI - Understanding prostate-specific antigen dynamics in monitoring metastatic castration-resistant prostate cancer: implications for clinical practice. AB - Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC) has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen (PSA). However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC. PMID- 27270340 TI - Induction of ultra-morphological features of apoptosis in mature and immature sperm. AB - There is a fundamental body of evidence suggesting that activated apoptosis signaling in ejaculated human sperm negatively influences their fertilization potential. However, it is still controversial whether this apoptotic signaling is a relic of an abortive apoptosis related to spermatogenesis or if it should be regarded as a functional preformed pathway in mature sperm leading to stereotypical morphological changes reflecting nuclear disassembly. To address this question, apoptosis was induced using betulinic acid in mature and immature ejaculated human sperm enriched by density gradient centrifugation. Execution of apoptosis was monitored by observing ultra-morphological changes via transmission electron microscopy. Typical morphological signs of apoptosis in somatic cells include plasma membrane blebbing with the formation of apoptotic bodies, impaired mitochondrial integrity, defects of the nuclear envelope, and nuclear fragmentation; these morphologies have also been observed in human sperm. In addition, these apoptotic characteristics were more frequent in immature sperm compared to mature sperm. Following betulinic acid treatment, apoptosis-related morphological changes were induced in mature sperm from healthy donors. This effect was much less pronounced in immature sperm. Moreover, in both fractions, the betulinic acid treatment increased the percentage of acrosome-reacted sperm. The results of our ultra-morphological study prove the functional competence of apoptosis in mature ejaculated human sperm. The theory of a sole abortive process may be valid only for immature sperm. The induction of the acrosome reaction by stimulating apoptosis might shed light on the biological relevance of sperm apoptosis. PMID- 27270341 TI - Genetic factors contributing to human primary ciliary dyskinesia and male infertility. AB - Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder resulting from the loss of normal ciliary function. Symptoms include neonatal respiratory distress, chronic sinusitis, bronchiectasis, situs inversus, and infertility. However, only 15 PCD-associated genes have been identified to cause male infertility to date. Owing to the genetic heterogeneity of PCD, comprehensive molecular genetic testing is not considered the standard of care. Here, we provide an update of the progress on the identification of genetic factors related to PCD associated with male infertility, summarizing the underlying molecular mechanisms, and discuss the clinical implications of these findings. Further research in this field will impact the diagnostic strategy for male infertility, enabling clinicians to provide patients with informed genetic counseling, and help to adopt the best course of treatment for developing directly targeted personalized medicine. PMID- 27270342 TI - Chloride channels are involved in sperm motility and are downregulated in spermatozoa from patients with asthenozoospermia. AB - Human spermatozoa encounter an osmotic decrease from 330 to 290 mOsm l-1 when passing through the female reproductive tract. We aimed to evaluate the role of chloride channels in volume regulation and sperm motility from patients with asthenozoospermia. Spermatozoa were purified using Percoll density gradients. Sperm volume was measured as the forward scatter signal using flow cytometry. Sperm motility was analyzed using computer-aided sperm analysis (CASA). When transferred from an isotonic solution (330 mOsm l-1 ) to a hypotonic solution (290 mOsm l-1 ), cell volume was not changed in spermatozoa from normozoospermic men; but increased in those from asthenozoospermic samples. The addition of the chloride channel blockers, 4,4'-diisothiocyanatostilbene-2,2'- isulfonic acid (DIDS) or 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) to the hypotonic solution caused the normal spermatozoa to swell but did not increase the volume of those from the asthenozoospermic semen. DIDS and NPPB decreased sperm motility in both sets of semen samples. The inhibitory effect of NPPB on normal sperm motility was much stronger than on spermatozoa from the asthenozoospermic samples. Both sperm types expressed ClC-3 chloride channels, but the expression levels in the asthenozoospermic samples were much lower, especially in the neck and mid-piece areas. Spermatozoa from men with asthenozoospermia demonstrated lower volume regulating capacity, mobility, and ClC-3 expression levels (especially in the neck) than did normal spermatozoa. Thus, chloride channels play important roles in the regulation of sperm volume and motility and are downregulated in cases of asthenozoospermia. PMID- 27270343 TI - Prostate-associated gene 4 (PAGE4), an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer. AB - Prostate-associated gene 4 (PAGE4) is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein (IDP) that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c Jun. c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer (PCa). Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease. PMID- 27270344 TI - Translation of genomics and epigenomics in prostate cancer: progress and promising directions. PMID- 27270346 TI - The ultrastructure of rabbit sclera after scleral crosslinking with riboflavin and blue light of different intensities. AB - PURPOSE: We aimed to determine the ultrastructural changes of collagen fibrils and cells in the rabbit sclera after scleral crosslinking using riboflavin and blue light of different intensities. Scleral crosslinking is known to increase scleral stiffness and may inhibit the axial elongation of progressive myopic eyes. METHODS: The equatorial parts of the sclera of one eye of six adult albino rabbits were treated with topical riboflavin solution (0.5 %) followed by irradiation with blue light (200, 400, 650 mW/cm(2)) for 20 min. After 3 weeks, the ultrastructure of scleral cells and the abundance of small- (10-100 nm) and large-diameter (>100 nm) collagen fibrils in fibril bundles of different scleral layers were examined with electron microscopy. RESULTS: In the scleral stroma of control eyes, the thickness of collagen fibrils showed a bimodal distribution. The abundance of small-diameter collagen fibrils decreased from the inner towards the outer sclera, while the amount of large-diameter fibrils and the scleral collagen content did not differ between different stroma layers. Treatment with riboflavin and blue light at 200 mW/cm(2) did not induce ultrastructural changes of cells and collagen fibrils in the scleral stroma. Treatment with blue light of higher intensities induced scleral cell activation in a scleral layer-dependent manner. In addition, outer scleral layers contained phagocytes that engulfed collagen fibrils and erythrocytes. Blue light of the highest intensity induced a reduction of the scleral collagen content, a decreased abundance of large diameter collagen fibrils, and an increased amount of small-diameter fibrils in the whole scleral stroma. CONCLUSIONS: The data indicate that in rabbits, scleral crosslinking with riboflavin and blue light of 200 mW/cm(2) for 20 min is relatively safe and does not induce ultrastructural alterations of scleral cells and of the collagen composition of the scleral stroma. Irradiation with blue light of intensities between 200 and 400 mW/cm(2) induces scleral cell activation, which may contribute to scleral scarring and stiffening. Higher intensities cause scleritis. PMID- 27270347 TI - Intravitreal bevacizumab injections combined with laser photocoagulation for adult-onset Coats' disease. PMID- 27270345 TI - Cutaneous lupus erythematosus: updates on pathogenesis and associations with systemic lupus. AB - PURPOSE OF REVIEW: Cutaneous lupus erythematosus (CLE) is a common manifestation among systemic lupus patients. There are no U.S. Food and Drug Administration approved therapies for CLE, and these lesions are frequently disfiguring and refractory to treatment. The present review will cover the recent inroads made into understanding the mechanisms behind CLE lesions and discuss promising therapeutic developments. RECENT FINDINGS: The definition of cutaneous lupus is being refined to facilitate diagnostic and research protocols. Research into the pathogenesis of CLE is accelerating, and discoveries are now identifying genetic and epigenetic changes which may predispose to particular disease manifestations. Furthermore, unique features of disease subtypes are being defined. Murine work supports a connection between cutaneous inflammation and systemic lupus disease activity. Importantly, human trials of type I interferon blockade hold promise for improving our treatment armamentarium for refractory CLE lesions. SUMMARY: Continued research to understand the mechanisms driving CLE will provide new methods for prevention and treatment of cutaneous lesions. These improvements may also have important effects on systemic disease activity, and thus, efforts to understand this link should be supported. PMID- 27270349 TI - Myofascial Trigger Point Release Massage Therapy Relieves Tension-Type Headaches. PMID- 27270350 TI - Spinal Manipulation Unable to Demonstrate Improved Sensorimotor Function. PMID- 27270351 TI - Using Osteopathic Manipulative Therapy to Influence Autonomic Nervous System Activity. PMID- 27270348 TI - Clinical Outcome From Oxaliplatin Treatment in Stage II/III Colon Cancer According to Intrinsic Subtypes: Secondary Analysis of NSABP C-07/NRG Oncology Randomized Clinical Trial. AB - IMPORTANCE: Oxaliplatin added to fluorouracil plus leucovorin therapy for patients with colon cancer has been shown to provide significant but modest absolute benefit for disease-free survival. However, acute and chronic neurotoxic effects from this regimen underscore the need for markers that predict oxaliplatin benefit. OBJECTIVE: To test our hypothesis that molecular subtypes of colon cancer would be associated with differential prognosis and benefit from oxaliplatin added to fluorouracil plus leucovorin therapy. DESIGN, SETTING, AND PARTICIPANTS: Participants in the NSABP C-07 trial were divided into discovery (n = 848) and validation (n = 881) cohorts based on the order of tissue block submission. A reestimated centroid using 72 genes was used to determine Colorectal Cancer Assigner subtypes and their association with oxaliplatin benefit in the discovery cohort. The validation cohort was examined with a locked down algorithm for subtype classification and statistical analysis plan. Post hoc analysis included examination of the entire cohort with Colorectal Cancer Assigner, Colorectal Cancer Subtype (CCS), and Consensus Molecular Subtype (CMS) methods. INTERVENTIONS: Fluorouracil plus leucovorin with or without oxaliplatin. MAIN OUTCOMES AND MEASURES: Percent recurrence-free survival. RESULTS: Among 1729 patients, 744 (43%) were female and mean (SD) age was 58 (11) years. Although C 07 participants with stage III disease with an enterocyte subtype showed a statistically significant benefit from oxaliplatin in the discovery cohort (hazard ratio, 0.22 [95% CI, 0.09-0.56]; P = .001 [N = 65]), no statistically significant benefit was observed in the validation cohort (hazard ratio, 0.53 [95% CI, 0.22-1.24]; P = .14 [N = 70]). The stemlike subtype was associated with poor prognosis and lack of benefit from oxaliplatin treatment (HR, 0.99 [95% CI, 0.73-1.34]; P = .96 [N = 367]). Examination of the different subtyping methods shows that all 3 methods robustly identified patients with poor prognosis (stemlike, CCS-3, and CMS-4) in both stage II and III. CONCLUSIONS AND RELEVANCE: Patients with stemlike tumors may be appropriate for clinical trials testing experimental therapies because stemlike tumors were robustly identified and associated with a poor prognosis regardless of stage or chemotherapy regimen. The clinical utility of using subtyping for the identification of patients for treatment with oxaliplatin requires validation in independent clinical trial cohorts. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00004931. PMID- 27270352 TI - Muscle Energy Technique Improves Chronic Lateral Epicondylitis. PMID- 27270353 TI - As the Twig Is Bent, so Grows the Tree-Part 5: In a Single Hospital, OMTh Shortens Length of Stay in the Neonatal Intensive Care Unit. PMID- 27270354 TI - As the Twig Is Bent, so Grows the Tree-Part 6: In a Multicenter Study, OMTh Shortens Length of Stay in the Neonatal Intensive Care Unit. PMID- 27270355 TI - As the Twig Is Bent, so Grows the Tree-Part 7: Severe Temporal Bone Restriction in Children Is Risk Factor for Acute Otitis Media. PMID- 27270356 TI - Highly transparent, low-haze, hybrid cellulose nanopaper as electrodes for flexible electronics. AB - Paper is an excellent candidate to replace plastics as a substrate for flexible electronics due to its low cost, renewability and flexibility. Cellulose nanopaper (CNP), a new type of paper made of nanosized cellulose fibers, is a promising substrate material for transparent and flexible electrodes due to its potentially high transparency and high mechanical strength. Although CNP substrates can achieve high transparency, they are still characterized by high diffuse transmittance and small direct transmittance, resulting in high optical haze of the substrates. In this study, we proposed a simple methodology for large scale production of high-transparency, low-haze CNP comprising both long cellulose nanofibrils (CNFs) and short cellulose nanocrystals (CNCs). By varying the CNC/CNF ratio in the hybrid CNP, we could tailor its total transmittance, direct transmittance and diffuse transmittance. By increasing the CNC content, the optical haze of the hybrid CNP could be decreased and its transparency could be increased. The direct transmittance and optical haze of the CNP were 75.1% and 10.0%, respectively, greatly improved from the values of previously reported CNP (31.1% and 62.0%, respectively). Transparent, flexible electrodes were fabricated by coating the hybrid CNP with silver nanowires (AgNWs). The electrodes showed a low sheet resistance (minimum 1.2 Omega sq(-1)) and a high total transmittance (maximum of 82.5%). The electrodes were used to make a light emitting diode (LED) assembly to demonstrate their potential use in flexible displays. PMID- 27270357 TI - Retraction Note to: Fibroblast growth factor receptor 4 polymorphisms and coronary artery disease: a case control study. PMID- 27270358 TI - Retraction Note to: Fibroblast growth factor receptor 4 polymorphisms and the prognosis of non-Hodgkin lymphoma. PMID- 27270359 TI - Tissue expression analysis, cloning and characterization of the 5'-regulatory region of the bovine FABP3 gene. AB - Fatty acid binding protein 3 (FABP3) is a member of the FABP family which bind fatty acids and have an important role in fatty acid metabolism. A large number of studies have shown that the genetic polymorphisms of FABP3 are positively correlated with intramuscular fat (IMF) content in domestic animals, however, the function and transcriptional characteristics of FABP3 in cattle remain unclear. Real-time PCR analysis revealed that bovine FABP3 was highly expressed in cardiac tissue. The 5'-regulatory region of bovine FABP3 was cloned and its transcription initiation sites were identified. Sequence analysis showed that many transcriptional factor binding sites including TATA-box and CCAAT-box were present on the 5'-flanking region of bovine FABP3, and four CpG islands were found on nucleotides from -891 to +118. Seven serial deletion constructs of the 5'-regulatory region evaluated in dual-luciferase reporter assay indicated that its core promoter was 384 base pairs upstream from the transcription initiation site. The transcriptional factor binding sites RXRalpha, KLF15, CREB and Sp1 were conserved in the core promoter of cattle, sheep, pigs and dogs. These results provide further understanding of the function and regulation mechanism of bovine FABP3. PMID- 27270360 TI - Educating the Primary Care Clinician on Preexposure Prophylaxis for Human Immunodeficiency Virus: A Teachable Moment. PMID- 27270361 TI - Rabies vaccination at a virus-inoculated site as an alternative option to rabies immunoglobulin. AB - Combined active and passive immunization has been established to be an optimal strategy for rabies post-exposure prophylaxis (PEP). Prompt administration of vaccine and rabies immunoglobulin (RIG) can reliably prevent the disease. However, RIG is unavailable and unaffordable in the majority of cases. On the basis of a model experiment using hamsters, we demonstrated that vaccine injection at the wound site in the same manner as administration of RIG provided protective efficacy that was not inferior to the current optimal PEP, a combination of vaccination and RIG. Further study is needed to determine whether it can replace the use of RIG. PMID- 27270362 TI - Significant decrease in peripheral regulatory B cells is an immunopathogenic feature of dermatomyositis. AB - Regulatory B cells (Bregs) are critical in maintaining self-tolerance. Their role in dermatomyositis (DM), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. In the current study, we performed flow cytometry analysis of studied CD19(+) CD24(high)CD38(high) Breg subpopulations in blood samples from 30 patients with DM, 37 diseased controls and 23 healthy controls. A significant decrease was observed in the frequency of Bregs in DM patients compared to that in diseased controls (p < 0.0001) and in healthy controls (p < 0.0001). And the prevalence of Bregs deficiency (defined as Bregs/B cells < 0.50% in this study) in DM patients went as high as 73.3%. Furthermore, DM patients with positive myositis specific autoantibody often had lower Bregs levels than negative patients (p = 0.036), and lower level of Bregs was also found in DM patients with interstitial lung disease than in DM patients without (p = 0.041). In a follow-up study, seven DM patients were considered to be in remission stage, and their Breg levels were found to have significantly increased after treatment (p = 0.022). Our research revealed that Breg deficiency is an immunopathogenic feature of DM and provided insights into the design of new immunotherapy target for DM clinical interventions. PMID- 27270363 TI - Reply. PMID- 27270364 TI - Conversion to Aflibercept After Prior Anti-VEGF Therapy for Persistent Diabetic Macular Edema. PMID- 27270381 TI - Advanced and flexible multi-carrier receiver architecture for high-count multi core fiber based space division multiplexed applications. AB - Space division multiplexing (SDM), incorporating multi-core fibers (MCFs), has been demonstrated for effectively maximizing the data capacity in an impending capacity crunch. To achieve high spectral-density through multi-carrier encoding while simultaneously maintaining transmission reach, benefits from inter-core crosstalk (XT) and non-linear compensation must be utilized. In this report, we propose a proof-of-concept unified receiver architecture that jointly compensates optical Kerr effects, intra- and inter-core XT in MCFs. The architecture is analysed in multi-channel 512 Gbit/s dual-carrier DP-16QAM system over 800 km 19 core MCF to validate the digital compensation of inter-core XT. Through this architecture: (a) we efficiently compensates the inter-core XT improving Q-factor by 4.82 dB and (b) achieve a momentous gain in transmission reach, increasing the maximum achievable distance from 480 km to 1208 km, via analytical analysis. Simulation results confirm that inter-core XT distortions are more relentless for cores fabricated around the central axis of cladding. Predominantly, XT induced Q penalty can be suppressed to be less than 1 dB up-to -11.56 dB of inter-core XT over 800 km MCF, offering flexibility to fabricate dense core structures with same cladding diameter. Moreover, this report outlines the relationship between core pitch and forward-error correction (FEC). PMID- 27270382 TI - Induction of protective immunity against experimental Eimeria tenella infection using serum exosomes. AB - Avian coccidiosis is caused by Eimeria, a unicellular, apicomplexan protist which primarily infects intestinal epithelia resulting in nutrient malabsorption and reduced growth of commercial poultry. Vaccination of chickens with exosomes isolated from antigen presenting cells containing parasite antigens (Ags) represents a promising alternative strategy to control avian coccidiosis, but is restricted in its commercial application due to limitations on production scale up for mass immunization programs. Here, we report the biochemical and physiologic characteristics of exosomes derived from serum of Eimeria tenella infected chickens and their feasibility for inducing protective immunity to experimental coccidiosis. Exosomes isolated from the serum of E. tenella-infected chickens contained a subset of protein Ags found in the intact parasite. Serum derived exosomes containing these E. tenella Ags localized to the intestine and spleen following intramuscular injection into naive chickens. In vitro ELISPOT assays revealed increased numbers of IL-2-, IL-4-, IL-6-, and IFN-gamma-secreting cells in the intestine and spleen of exosome-administered chickens, compared with vehicle controls. Pre-immunization of chickens with serum exosomes from E. tenella-infected chickens increased both body weight gain and feed conversion efficiency, and reduced both fecal parasite shedding and gut lesion scores following parasite infection, compared with vehicle controls. Finally, immunization with CD80(+) serum exosomes stimulated greater numbers of cytokine producing cells, and higher levels of protective immunity to E. tenella infection, compared with CD80(-) exosomes. These results suggest the possibility of producing an effective, parasite-free vaccine against avian coccidiosis under field conditions using serum-derived CD80(+) exosomes containing parasite Ags. PMID- 27270383 TI - Prevalence of vector-borne pathogens in dogs from Haiti. AB - Canine vector-borne pathogens are common on some Caribbean islands, but survey data in Haiti are lacking. To determine the prevalence of selected vector-borne pathogens in dogs from Haiti, we tested blood samples collected from 210 owned dogs, 28 (13.3%) of which were infested with Rhipicephalus sanguineus ticks at the time of blood collection. No other tick species were identified on these dogs. A commercially available ELISA identified antibodies to Ehrlichia spp. in 69 (32.9%), antibodies to Anaplasma spp. in 37 (17.6%), and antigen of Dirofilaria immitis in 55 (26.2%); antibodies to Borrelia burgdorferi were not detected in any sample. Molecular assays of whole blood from 207 of the dogs confirmed infection with Ehrlichia canis (15; 7.2%), Anaplasma platys (13; 6.3%), D. immitis (46; 22.2%), Wolbachia spp. (45; 21.7%), Babesia vogeli (16; 7.7%), and Hepatozoon canis (40; 19.3%), but Anaplasma phagocytophilum, Babesia canis, Babesia rossi, Babesia gibsoni, Ehrlichia chaffeensis, Ehrlichia ewingii, or Hepatozoon americanum were not detected. Co-infection with two or more vector borne pathogens was detected by serology in 42 (20.0%) dogs and by molecular assays in 22 (10.6%) dogs; one dog was co-infected with B. vogeli and E. canis as detected by PCR with D. immitis detected by serology (antigen). Overall, evidence of past or current infection with at least one vector-borne pathogen was identified in 142/210 (67.6%) dogs in this study, underscoring the common nature of these pathogens, some of which are zoonotic, in Haiti. PMID- 27270384 TI - Immunization with Fasciola hepatica thioredoxin glutathione reductase failed to confer protection against fasciolosis in cattle. AB - The liver fluke Fasciola hepatica remains an important agent of food-borne trematode disease producing great economic losses due to its negative effect on productivity of livestock grazing in temperate areas. The prevailing control strategy based on anthelmintic drugs is unsustainable due to widespread resistance hence vaccination appears as an attractive option to pursue. In this study we evaluate the effect of vaccination in calves with a functional recombinant thioredoxin glutathione reductase (rFhTGR) from liver fluke, a critical antioxidant enzyme at the crossroads of the thioredoxin and glutathione metabolism in flatworms. The recombinant enzyme produced in Escherichia coli was tested in two vaccination experiments; in the first trial rFhTGR was administered in combination with Freunds Incomplete Adjuvant (FIA) in a three-inoculation scheme on weeks 0, 4 and 8; in the second trial rFhTGR was given mixed with Adyuvac 50 or Alum as adjuvants on weeks 0 and 4. In both cases calves were challenged with metacercariae (400 in the first and 500 in the second trial) 2 weeks after the last inoculation. Our results demonstrate that two or three doses of the vaccine induced a non-significant reduction in worm counts of 8.2% (FIA), 3.8% (Adyuvac 50) and 23.0% (Alum) compared to adjuvant controls indicating that rFhTGR failed to induce a protective immunity in challenged calves. All vaccine formulations induced a mixed IgG1/IgG2 response but no booster was observed after challenge. No correlations between antibody titres and worm burdens were found. PMID- 27270385 TI - Population genetic analysis of Theileria parva isolated in cattle and buffaloes in Tanzania using minisatellite and microsatellite markers. AB - A population genetic study of Theileria parva was conducted on 103 cattle and 30 buffalo isolates from Kibaha, Lushoto, Njombe Districts and selected National parks in Tanzania. Bovine blood samples were collected from these study areas and categorized into 5 populations; Buffalo, Cattle which graze close to buffalo, Kibaha, Lushoto and Njombe. Samples were tested by nested PCR for T. parva DNA and positives were compared for genetic diversity to the T. parva Muguga vaccine reference strain, using 3micro and 11 minisatellite markers selected from all 4 chromosomes of the parasite genome. The diversity across populations was determined by the mean number of different alleles, mean number of effective alleles, mean number of private allele and expected heterozygosity. The mean number of allele unique to populations for Cattle close to buffalo, Muguga, Njombe, Kibaha, Lushoto and Buffalo populations were 0.18, 0.24, 0.63, 0.71, 1.63 and 3.37, respectively. The mean number of different alleles ranged from 6.97 (Buffalo) to 0.07 (Muguga). Mean number of effective alleles ranged from 4.49 (Buffalo) to 0.29 (Muguga). The mean expected heterozygosity were 0.07 0.29, 0.45, 0.48, 0.59 and 0.64 for Muguga, cattle close to buffalo, Kibaha, Njombe, Lushoto and Buffalo populations, respectively. The Buffalo and Lushoto isolates possessed a close degree of diversity in terms of mean number of different alleles, effective alleles, private alleles and expected heterozygosity. The study revealed more diversity in buffalo isolates and further studies are recommended to establish if there is sharing of parasites between cattle and buffaloes which may affect the effectiveness of the control methods currently in use. PMID- 27270386 TI - Pasture is a risk factor for Toxoplasma gondii infection in fattening pigs. AB - As consumer awareness of animal welfare increases throughout Europe, housing of pigs in more animal-friendly systems is becoming more common. There is concern that these free-range and organic management systems increase the prevalence of zoonotic meat-borne pathogens, such as Toxoplasma gondii. In this study we compared the seroprevalence of T. gondii between commercial fattening pigs raised on conventional and on organic farms in Sweden. Furthermore, potential associations between presence of T. gondii antibodies and type of production, access to pasture, and geographical region were analysed. A significant difference in T. gondii seroprevalence was found between conventional (1%) and organic pigs (8%). The higher odds of seropositivity in organic production was attributed to pasture access specifically (OR=1.8 for a one-month increase in length of pasture exposure). This study shows that the prevalence of T. gondii in Swedish conventional pigs is low. However, as pigs with access to pasture are at higher risk of infection and because the demand for animal-friendly production systems is increasing, there is an obvious need to practically manage the higher T. gondii presence in products from pigs raised in organic systems with outdoor access. PMID- 27270387 TI - The in vitro effect of prolactin on the growth, motility and expression of prolactin receptors in larvae of Toxocara canis. AB - The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3+/-0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species. PMID- 27270388 TI - Acaricidal activity of the organic extracts of thirteen South African plants against Rhipicephalus (Boophilus) decoloratus (Acari: Ixodidae). AB - The African blue tick, Rhipicephalus (Boophilus) decoloratus, is a common tick species found in South Africa and affects cattle production as well as vectoring pathogens in regions of Africa and Asia. In an attempt to develop a non-toxic, lower cost and environmentally friendly tick control method, twenty-six plant extracts were prepared from thirteen plant species using 99.5% acetone and 99% ethanol. The adapted Shaw Larval Immersion Test (SLIT) was used to test the efficacy of the extracts. A 1% solution of each of the plant extracts was prepared for efficacy testing and the ethanol extracts were found to have better acaricidal activity than the acetone extracts. The ethanol extract from the leaves and flowers of Calpurnia aurea had the best activity [corrected mortality (CM)=82.9%] which was followed by the stem extract of Cissus quadrangularis (CM=80.4%). The plant species were screened against Vero cells and were found to have low toxicity. From this study it is apparent that there is potential for the development of botanicals as natural acaricides against R. (B.) decoloratus. PMID- 27270389 TI - Vector-borne pathogens in dogs and red foxes from the federal state of Brandenburg, Germany. AB - Dirofilaria repens is endemic in eastern and southern European regions but was recently found in Germany in dogs, mosquitoes and one human patient. Since some of the positive dog and mosquito samples were collected in Brandenburg, it was aimed to systematically assess the prevalence of D. repens and other canine vector-borne pathogens in Brandenburg. Dog owners also received a questionnaire and were asked to provide more information about the dogs including travel history. In total, 1023 dog blood samples as well as 195 fox spleen and 179 fox blood samples were collected. DNA was analysed by PCR for the presence of filariae, piroplasms, anaplasmataceae and Rickettsia spp. Filariae were detected in six dogs (0.6%), two were positive for DNA from D. repens, two from Dirofilaria immitis and two from Acanthocheilonema reconditum. One of the D. repens positive dogs originated from an animal shelter in Brandenburg, but the origin of the other one remained unknown. Interestingly, both D. repens ITS-1 sequences showed 100% identity to a D. repens sample obtained from a Japanese woman that travelled in Europe and were 97% identical to a newly proposed species Dirofilaria sp. 'hongkongensis' described from Hong Kong. However, identity to other D. repens sequences from Thailand was considerably lower (81%). Identity of 12S rRNA and cytochrome oxidase I to D. repens samples from southern Europe was 99%. Due to the low number of Dirofilaria spp. positive dogs and since the origin of these was unknown, endemic occurrence of Dirofilaria in Brandenburg could not be confirmed. Anaplasma phagocytophilum was found in 15 dogs (1.5%), Candidatus Neoehrlichia mikurensis in three dogs (0.3%) and E. canis in one dog (0.1%), which was co-infected with D. repens. Rickettsia spp. were detected in 8 dogs (0.8%), seven were Rickettsia raoultii and one was Rickettsia felis. To the author's knowledge, R. raoultii DNA was detected for the first time in dogs in Germany in this study and Candidatus N. mikurensis for the second time. In spleen samples of red foxes with 47.5% a high prevalence of piroplasms was found. Sequencing of 11 samples identified 10 as Theileria annae. Despite the high prevalence of this pathogen in its reservoir host, it was absent in dog samples. In one dog (0.1%), Babesia canis was detected but there was no further information about the dog's origin. Evaluation of the questionnaire identified a high proportion of dogs (74.2%, n=233) which was not protected by ectoparasiticides. Moreover, 21.2% (n=236) of the dogs originated from inland or abroad shelters, and therefore might potentially come from areas endemic for dirofilariosis or babesiosis. PMID- 27270390 TI - Toxoplasma gondii: Pig seroprevalence, associated risk factors and viability in fresh pork meat. AB - This study was conducted on 161 fattening pig farms located in Aragon (Northeast Spain). Serum samples from 1200 pigs were tested for antibodies against T. gondii by indirect immunofluorescence assay (IFA). Antibodies to T. gondii (>=1:20) were detected in 301 pigs (24.52%). The seroprevalence observed in the present study indicates a widespread exposure to T. gondii, as seropositive pigs were found in 96.67% of the farms studied although low pig titers were determined. Risk factors associated with T. gondii seroprevalence were presence of cats in or around the farms, presence of dogs around the facilities, low number of animals in the farms, poor hygiene and bad maintenance of the farms. Finally, it was observed that where rodent baits were used, Toxoplasma prevalence was lower. Risk management measures including control of cats and rodents on the farms, among others, could help to reduce the observed prevalence levels. By mouse bioassay, T. gondii was detected in 73.7% and isolated from 42.1% of seropositive pigs and a significant relation between the titers of pigs and the presence and viability of T. gondii in the tissues was found. The detection of T. gondii is not possible by currently practiced meat inspection. Nevertheless, the increased probability of detecting viable forms of T. gondii in tissues of pigs with titers >=1: 80 could be used as the cutoff for discriminating higher risk animals, and could be used as an effective control tool for the industry of cured meat products. In practical terms, we propose that this value could be used as a critical limit in the HACCP system. PMID- 27270391 TI - First report of parasitism by Hexametra boddaertii (Nematoda: Ascaridae) in Oxyrhopus guibei (Serpentes: Colubridae). AB - The current study summarizes the postmortem examination of a specimen of Oxyrhopus guibei (Serpentes, Colubridae) collected in Iguazu National Park (Argentina), and found deceased a week following arrival to the serpentarium of the National Institute of Tropical Medicine (Argentina). Although the snake appeared to be in good health, a necropsy performed following its death identified the presence of a large number of roundworms in the coelomic cavity, with indications of peritonitis and serosal adherence. Additional observations from the necropsy revealed small calcifications in the mesothelium of the coelomic cavity; solid and expressive content in the gallbladder; massive gastrointestinal obstruction due to nematodes; and lung edema and congestion. Histopathological analyses of lung sections also showed proliferative heterophilic and histiocytic pneumonia. Parasites isolated from both the intestine and coelomic cavity were identified as Hexametra boddaertii by a combination of light and scanning electron microscopic examination. Results from this necropsy identify O. guibei as a new host for H. boddaertii, and is the first report of a natural infection by Hexametra in Argentina. Since Hexametra parasites may contribute to several pathological conditions in humans, and with the recent availability of O. guibei specimens through the illegal pet trade, it is necessary to consider the possibility of zoonotic helminth transmission of Hexametra from snake to human. PMID- 27270392 TI - Standardization and application of the tetraprimer ARMS-PCR technique for screening of the E198A SNP in the beta-tubulin gene of hookworm populations in Brazil. AB - The tetraprimer ARMS-PCR technique is efficient for SNP detection and can be used to search for polymorphisms associated with drug resistance. However, the establishment of this methodology is not always straightforward because of the constraints on primer design due to the restrictions of the polymorphic regions. Here, we describe the standardization of the tetraprimer ARMS-PCR methodology for the detection of a SNP at codon 198 of the Ancylostoma caninum beta-tubulin gene. This SNP is associated with resistance to albendazole in various nematodes. The methodology was used to screen 327 individuals from 6 different locations. No mutation was found in any of the samples. This methodology will be useful for screening for the E198A SNP in the beta-tubulin gene of canine hookworms in a broader population to determine whether this SNP is associated with benzimidazole resistance in this species. The method could also be adapted for the analysis of other SNPs in other nematode species. PMID- 27270393 TI - Primary screen for potential sheep scab control agents. AB - The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole). PMID- 27270394 TI - Evaluation of ionophore sensitivity of Eimeria acervulina and Eimeria maxima isolated from the Algerian to Jijel province poultry farms. AB - The present study represents the first description of ionophore resistance in recovered from commercial Algerian (Jijel-Algeria) broiler farms. Microscopy and intervening transcribed sequence 1 PCR (ITS1 PCR) revealed only 2 Eimeria species present in litter from these farms- namely Eimeria acervulina and Eimeria maxima. A pool of these isolates were evaluated in broiler chickens (Cobb 500) for sensitivity to 5 anticoccidial compounds-diclazuril (1ppm), lasalocid (125ppm), monensin (125ppm), narasin (70ppm) and salinomycin (60ppm). As indicated by anticoccidial sensitivity profiles based on lesion scores and anticoccidial index (ACI), complete resistance to monensin and narasin, partial resistance to salinomycin and lasalocid, and complete sensitivity to diclazuril was observed. While lack of sensitivity to monensin is not surprising given its use for years as the sole anticoccidial compound, the resistance to monoether (narasin) and polyether (lasalocid) ionophores suggests that cross-resistance has developed in a segment of the Eimeria population. The fairly uniform Eimeria species composition among all poultry farms suggests that E. acervulina and E. maxima more rapidly develop resistance to ionophore drugs. PMID- 27270395 TI - Predicting the potential environmental suitability for Theileria orientalis transmission in New Zealand cattle using maximum entropy niche modelling. AB - The tick-borne haemoparasite Theileria orientalis is the most important infectious cause of anaemia in New Zealand cattle. Since 2012 a previously unrecorded type, T. orientalis type 2 (Ikeda), has been associated with disease outbreaks of anaemia, lethargy, jaundice and deaths on over 1000 New Zealand cattle farms, with most of the affected farms found in the upper North Island. The aim of this study was to model the relative environmental suitability for T. orientalis transmission throughout New Zealand, to predict the proportion of cattle farms potentially suitable for active T. orientalis infection by region, island and the whole of New Zealand and to estimate the average relative environmental suitability per farm by region, island and the whole of New Zealand. The relative environmental suitability for T. orientalis transmission was estimated using the Maxent (maximum entropy) modelling program. The Maxent model predicted that 99% of North Island cattle farms (n=36,257), 64% South Island cattle farms (n=15,542) and 89% of New Zealand cattle farms overall (n=51,799) could potentially be suitable for T. orientalis transmission. The average relative environmental suitability of T. orientalis transmission at the farm level was 0.34 in the North Island, 0.02 in the South Island and 0.24 overall. The study showed that the potential spatial distribution of T. orientalis environmental suitability was much greater than presumed in the early part of the Theileria associated bovine anaemia (TABA) epidemic. Maximum entropy offers a computer efficient method of modelling the probability of habitat suitability for an arthropod vectored disease. This model could help estimate the boundaries of the endemically stable and endemically unstable areas for T. orientalis transmission within New Zealand and be of considerable value in informing practitioner and farmer biosecurity decisions in these respective areas. PMID- 27270396 TI - Atypical Toxoplasma gondii genotype in feral cats from the Fernando de Noronha Island, northeastern Brazil. AB - Toxoplasma gondii isolates from Brazil have a different phenotypic and genotypic pattern, with predominance of virulent isolates and recombinant genotypes, compared to the North Hemisphere. Considering that a new T. gondii genotype, non pathogenic to mice, was previously identified from free-range chickens from the Fernando de Noronha Island, Brazil, this study aimed to identify genotypes of this parasite in tissue samples of feral cats (Felis catus) from this Brazilian Island. Anti-T. gondii IgG antibodies were detected in 18/31 (58%) feral cats. Two non-virulent T. gondii isolates were obtained by mouse bioassay. Genotyping was performed by PCR-RFLP using 10 genetic markers (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, PK1, L358 and Apico) and an atypical strain of T. gondii (ToxoDB #146) was identified. This is the first report of this genotype in feral cats. PMID- 27270397 TI - Transcriptional profiling of the ovine abomasal lymph node reveals a role for timing of the immune response in gastrointestinal nematode resistance. AB - Gastrointestinal nematodes are a serious cause of morbidity and mortality in grazing ruminants. The major ovine defence mechanism is acquired immunity, with protective immunity developing over time in response to infection. Nematode resistance varies both within and between breeds and is moderately heritable. A detailed understanding of the genes and mechanisms involved in protective immunity, and the factors that regulate this response, is required to aid both future breeding strategies and the development of effective and sustainable nematode control methods. The aim of this study was to compare the abomasal lymph node transcriptome of resistant and susceptible lambs in order to determine biological processes differentially expressed between resistant and susceptible individuals. Scottish Blackface lambs, with divergent phenotypes for resistance, were challenged with 30,000 Teladorsagia circumcincta larvae (L3), and abomasal lymph nodes recovered at 7 and 14days post-infection (dpi). High-throughput sequencing of cDNA from the abomasal lymph node was used to quantitatively sample the transcriptome with an average of 32 million reads per sample. A total of 194 and 144 genes were differentially expressed between resistant and susceptible lambs at 7 and 14 dpi respectively. Differentially expressed networks and biological processes were identified using Ingenuity Pathway Analysis. Genes involved in the inflammatory response, attraction of T lymphocytes and binding of leukocytes were more highly expressed in resistant animals at 7 dpi and in susceptible animals at 14 dpi indicating that resistant animals respond to infection earlier than susceptible animals. Twenty-four Single Nucleotide Polymorphisms (SNP) within 11 differentially expressed genes, were tested for association with gastrointestinal nematode resistance in the Scottish Blackface lambs. Four SNP, in 2 genes (SLC30A2 and ALB), were suggestively associated with faecal egg count. In conclusion, a large number of genes were differentially expressed in the abomasal lymph node of resistant and susceptible lambs responding to gastrointestinal nematode challenge. Resistant Scottish Blackface lambs appear to generate an earlier immune response to T. circumcincta. In susceptible lambs this response appears to be delayed. SNP in 2 differentially expressed genes were suggestively associated with faecal egg count indicating that differentially expressed genes may be considered candidate loci for mediating nematode resistance. PMID- 27270398 TI - Process and kinetics of azo dye decolourization in bioelectrochemical systems: effect of several key factors. AB - This study explored the influence of several key factors on the process and kinetics of azo dye decolourization in bioelectrochemical systems (BESs), including cathode potential, dissolved oxygen (DO) concentration of catholyte and biofilm formed on the cathode. The results show that azo dye methyl orange (MO) decolourization in the BES could be well described with the pseudo first-order kinetics. The MO decolourization efficiency increased from 0 to 94.90 +/- 0.01% and correspondingly the reaction rate constant increased from 0 to 0.503 +/- 0.001 h(-1) with the decrease in cathodic electrode potential from -0.2 to -0.8 V vs Ag/AgCl. On the contrary, DO concentration of the catholyte had a negative impact on MO decolourization in the BES. When DO concentration increased from zero to 5.80 mg L(-1), the MO decolourization efficiency decreased from 87.19 +/- 4.73% to 27.77 +/- 0.06% and correspondingly the reaction rate constant reduced from 0.207 +/- 0.042 to 0.033 +/- 0.007 h(-1). Additionally, the results suggest that the biofilm formed on the cathode could led to an adverse rather than a positive effect on azo dye decolourization in the BES in terms of efficiency and kinetics. PMID- 27270399 TI - Risk of Early Rehospitalization for Non-Behavioral Health Conditions Among Adult Medicaid Beneficiaries with Severe Mental Illness or Substance Use Disorders. AB - The goal was to examine risk factors and expenditures for early rehospitalization (within 30 days of discharge) for non-behavioral health conditions among Medicaid enrolled Floridians over 8 years. There were 1,689,797 hospitalization episodes with 19% (N = 314,742) resulting in early rehospitalization. Total gross charges for early rehospitalization were over 13 billion dollars. In Cox proportional hazards regression adjusted for demographic and health covariates, drug use disorder was associated with 50% increased risk of early rehospitalization. Having major depressive disorder increased risk by 17%; psychotic disorder, bipolar disorder, and alcohol use disorder increased risk of early rehospitalization slightly by 10, 6, and 6% respectively. The effect of dementia on risk was minimal at 2%. Risk of early rehospitalization decreased by 3.5% per year over the 8 years of the study. Attention to mental health problems, especially drug use disorder, may help further reduce rates of early readmission for non-behavioral health conditions. PMID- 27270400 TI - Control of the innate immune response by the mevalonate pathway. AB - Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110delta. Macrophages that were deficient in GGTase I or p110delta exhibited constitutive release of interleukin 1beta that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome. PMID- 27270401 TI - Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS. AB - Mutations in the genes encoding pyrin and mevalonate kinase (MVK) cause distinct interleukin-1beta (IL-1beta)-mediated autoinflammatory diseases: familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS). Pyrin forms an inflammasome when mutant or in response to bacterial modification of the GTPase RhoA. We found that RhoA activated the serine-threonine kinases PKN1 and PKN2 that bind and phosphorylate pyrin. Phosphorylated pyrin bound to 14-3-3 proteins, regulatory proteins that in turn blocked the pyrin inflammasome. The binding of 14-3-3 and PKN proteins to FMF-associated mutant pyrin was substantially decreased, and the constitutive IL-1beta release from peripheral blood mononuclear cells of patients with FMF or HIDS was attenuated by activation of PKN1 and PKN2. Defects in prenylation, seen in HIDS, led to RhoA inactivation and consequent pyrin inflammasome activation. These data suggest a previously unsuspected fundamental molecular connection between two seemingly distinct autoinflammatory disorders. PMID- 27270402 TI - Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses. AB - The number of naive T cells decreases and susceptibility to new microbial infections increases with age. Here we describe a previously unknown subset of phenotypically naive human CD8(+) T cells that rapidly secreted multiple cytokines in response to persistent viral antigens but differed transcriptionally from memory and effector T cells. The frequency of these CD8(+) T cells, called 'memory T cells with a naive phenotype' (TMNP cells), increased with age and after severe acute infection and inversely correlated with the residual capacity of the immune system to respond to new infections with age. CD8(+) TMNP cells represent a potential new target for the immunotherapy of persistent infections and should be accounted for and subtracted from the naive pool if truly naive T cells are needed to respond to antigens. PMID- 27270406 TI - Compensation effects and relation between the activation energy of spin transition and the hysteresis loop width for an iron(ii) complex. AB - The enthalpy-entropy compensation was observed for the cooperative -> spin transition (the phase is a mononuclear complex [FeL2](BF4)2, L is 4-(3,5-dimethyl 1H-pyrazol-1-yl)-2-(pyridin-2-yl)-6-methylpyrimidine). The physical origin of this effect is the fact that the -> spin transition is the first order phase transition accompanied by noticeable variations in the Tonset?, DeltaH and DeltaS values. Higher DeltaH and DeltaS values are correlated with higher Tonset? values. The higher the enthalpy and entropy of the spin transition, the wider the hysteresis loop. The kinetic compensation effect, i.e. a linear relationship between ln A and Ea, was observed for the -> spin transition. Moreover, an isokinetic relationship was detected in this system: the Arrhenius lines (ln k vs. 1/T) obtained from magnetochemical data for different samples of the phase undergoing the -> transition show a common point of intersection (Tiso = 490 +/- 2 K, ln kiso = -6.0 +/- 0.2). The validity of this conclusion was confirmed by the Exner-Linert statistical method. This means that the isokinetic relationship and the kinetic compensation effect (ln A vs. Ea) in this system are true ones. The existence of a true kinetic compensation effect is supported independently by the fact that the hysteresis loop width for the cooperative spin transition <-> increases with increasing activation barrier height. Estimating the energy of excitations for the phase with Tiso ~ 490 K yields wavenumbers of ca. 340 cm(-1) corresponding to the frequencies of the stretching vibrations of the Fe(LS)-N bonds, i.e. the bonds directly involved in the mechanism of the spin transition. This is the first observation of the kinetic compensation effect (ln A vs. Ea) and the isokinetic relationship for a cooperative spin crossover system showing thermal hysteresis. Our results provide the first experimental evidence that the higher the activation barrier for the spin transition, the wider the hysteresis loop for a series of related spin crossover systems. PMID- 27270403 TI - Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model. AB - Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0-450 kPa (0-800 Pa?s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146-220 kPa and 221-290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0-145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85-145 kPa. PMID- 27270405 TI - Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARalpha and SREBP-1c in L-02 Cells. AB - Excessive fat accumulation and increased oxidative stress contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the development of steatosis are not entirely understood. The present study was undertaken to establish an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the effects of oxidative stress could be studied in L-02 cells. We investigated the effects of free fatty acids (FFA) (palmitate:oleate, 1:2) on lipid accumulation and oxidative stress and their possible mechanisms in L-02 cells. High concentrations of fatty acids significantly induced excessive lipid accumulation and oxidative stress in L-02 cells, which could only be reversed with 50 MUMU WY14643 (the PPARalpha agonist). Immunoblotting and qPCR analyses revealed that FFA downregulated the expression of proliferator-activated receptor alpha (PPARalpha), which contributed to the increased activation of sterol regulatory element binding protein-1c (SREBP-1c). These results suggest that FFA induce lipid accumulation and oxidative stress in L-02 cells by upregulating SREBP-1c expression through the suppression of PPARalpha. PMID- 27270404 TI - Low Dietary c9t11-Conjugated Linoleic Acid Intake from Dairy Fat or Supplements Reduces Inflammation in Collagen-Induced Arthritis. AB - Dietary cis-9,trans-11 (c9t11) conjugated linoleic acid (CLA) fed at 0.5 % w/w was previously shown to attenuate inflammation in the murine collagen-induced (CA) arthritis model, and growing evidence implicates c9t11-CLA as a major anti inflammatory component of dairy fat. To understand c9t11-CLA's contribution to dairy fat's anti-inflammatory action, the minimum amount of dietary c9t11-CLA needed to reduce inflammation must be determined. This study had two objectives: (1) determine the minimum dietary anti-inflammatory c9t11-CLA intake level in the CA model, and (2) compare this to anti-inflammatory effects of dairy fat (non enriched, naturally c9t11-CLA-enriched, or c9t11-CLA-supplemented). Mice received the following dietary fat treatments (w/w) post arthritis onset: corn oil (6 % CO), 0.125, 0.25, 0.375, and 0.5 % c9t11-CLA, control butter (6 % CB), c9t11 enriched butter (6 % EB), or c9t11-CLA-supplemented butter (6 % SB, containing 0.2 % c9t11-CLA). Paw arthritic severity and pad swelling were scored and measured, respectively, over an 84-day study period. All c9t11-CLA and butter diets decreased the arthritic score (25-51 %, P < 0.01) and paw swelling (8-11 %, P < 0.01). Throughout the study, plasma tumor necrosis factor (TNFalpha) was elevated in CO-fed arthritic mice compared to non-arthritic (NA) mice but was reduced in 0.5 % c9t11-CLA- and EB-fed mice. Interleukin-1beta and IL-6 were increased in arthritic CO-fed mice compared to NA mice but were reduced in 0.5 % c9t11-CLA- and EB-fed mice through day 42. In conclusion, 0.125 % c9t11-CLA reduced clinical arthritis as effectively as higher doses, and decreased arthritis in CB-fed mice suggested that the minimal anti-inflammatory levels of c9t11-CLA might be below 0.125 %. PMID- 27270407 TI - SGLT2 inhibitors in the management of type 2 diabetes. AB - The glucose-lowering pharmacopeia continues to grow for patients with type 2 diabetes. The latest drug category, the SGLT2 inhibitors reduce glycated hemoglobin concentrations by increasing urinary excretion of glucose. They are used mainly in combination with metformin and other antihyperglycemic agents, including insulin. Their glucose-lowering potency is modest. Advantages include lack of hypoglycemia as a side effect, and mild reduction in blood pressure and body weight. Side effects include increased urinary frequency, owing to their mild diuretic action, symptoms of hypovolemia, genitourinary infections. There are also recent reports of rare cases of diabetic ketoacidosis occurring in insulin-treated patients. Recently, a large cardiovascular outcome trial reported that a specific SGLT2 inhibitor, empagliflozin, led to a reduction in the primary endpoint of major cardiovascular events. This effect was mainly the result of a surprising 38 % reduction in cardiovascular death, and the drug was also associated with nearly as large a reduction in heart failure hospitalization. These findings were notable because most drugs used in type 2 diabetes have not been shown to improve cardiovascular outcomes. Accordingly, there is growing interest in empagliflozin and the entire SGLT2 inhibitor class as drugs that could potentially change the manner in which we approach the management of hyperglycemia in patients with type 2 diabetes. PMID- 27270409 TI - Dynamic Kinetic Resolution Enabled by Intramolecular Benzoin Reaction: Synthetic Applications and Mechanistic Insights. AB - The highly enantio-, diastereo-, and regioselective dynamic kinetic resolution of beta-ketoesters and 1,3-diketones was achieved via a chiral N-heterocyclic carbene catalyzed intramolecular cross-benzoin reaction. A variety of tetralone derivatives bearing two contiguous stereocenters and multiple functionalities were liberated in moderate to excellent yields and with high levels of stereoselectivity (>95% ee and >20:1 dr in most cases). In addition, the excellent regioselectivity control for aryl/alkyl 1,3-diketones, and the superior electronic differentiation of 1,3-diarylketones were highlighted. Moreover, a set of new mechanistic rationale that differs with the currently widely accepted understanding of intramolecular benzoin reactions was established to demonstrate the superior preference of benzoin over aldol transformation: (1) A coexistence of competitive aldol and benzoin reactions was detected, but a retro-aldol irreversible benzoin process performs a vital role in the generation of predominant benzoin products. (2) The most essential role of an N-electron withdrawing substituent in triazolium catalysts was revealed to be accelerating the rate of the benzoin transformation, rather than suppressing the aldol process through reducing the inherent basicity of the catalyst. PMID- 27270408 TI - [Molecular and immunohistochemical diagnostics in melanoma]. AB - To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed. PMID- 27270411 TI - Major abdominal surgery in octogenarians: should high age affect surgical decision-making? AB - BACKGROUND: Over the last decades longevity has increased significantly, with more octogenarians undergoing surgery. Here, we assess surgical outcomes after major abdominal surgery in octogenarians. METHODS: Observational cohort of 874 patients undergoing major abdominal elective surgery between January 2009 and March 2014. Seventy-six octogenarians were propensity matched to 76 younger patients, corrected for sex, body mass index, American Society of Anesthesiologists classification, comorbidity, indication, and type of surgery. RESULTS: Minor complications were more prevalent in octogenarians (P = .01) and consisted mainly of respiratory complications; progressing to respiratory insufficiency requiring intubation in 28.6%. Preoperative weight loss (odds ratio 3 [1.1 to 8.3]) and upper gastrointestinal surgery (odds ratio 11 [2 to 60]) were associated with minor complications. CONCLUSIONS: Octogenarians are at increased risk of minor complications after major abdominal surgery. Major complication rates were similar, indicating the importance of preoperative assessment and standardized surgical techniques. Taking into account preoperative morbidities and type of surgery and techniques. Implementation of quality control algorithms may further improve outcomes in octogenarians. PMID- 27270413 TI - iPSC-derived LewisX+CXCR4+beta1-integrin+ neural stem cells improve the amyotrophic lateral sclerosis phenotype by preserving motor neurons and muscle innervation in human and rodent models. AB - Amyotrophic lateral sclerosis (ALS) is a fatal incurable neurodegenerative disease characterized by progressive degeneration of motor neurons (MNs), leading to relentless muscle paralysis. In the early stage of the disease, MN loss and consequent muscle denervation are compensated by axonal sprouting and reinnervation by the remaining MNs, but this mechanism is insufficient in the long term. Here, we demonstrate that induced pluripotent stem cell-derived neural stem cells (NSCs), in particular the subpopulation positive for LewisX-CXCR4 beta1-integrin, enhance neuronal survival and axonal growth of human ALS-derived MNs co-cultured with toxic ALS astrocytes, acting on both autonomous and non autonomous ALS disease features. Transplantation of this NSC fraction into transgenic SOD1G93A ALS mice protects MNs in vivo, promoting their ability to maintain neuromuscular junction integrity, inducing novel axonal sprouting and reducing macro- and microgliosis. These effects result in a significant increase in survival and an improved neuromuscular phenotype in transplanted SOD1G93A mice. Our findings suggest that effective protection of MN functional innervation can be achieved by modulation of multiple dysregulated cellular and molecular pathways in both MNs and glial cells. These pathways must be considered in designing therapeutic strategies for ALS patients. PMID- 27270412 TI - The associations between lifestyles and mental health using the General Health Questionnaire 12-items are different dependently on age and sex: a population based cross-sectional study in Kanazawa, Japan. AB - OBJECTIVES: The aim of this study was to examine potential differences of the associations between mental health and lifestyle factors across a wide range of age. METHODS: In August/September 2011, data were collected from 4693 males (age 51.6 +/- 19.5) and 5678 females (age 52.4 +/- 19.4) living in Kanazawa, Japan. A cross-sectional community-based survey was conducted with self-administered questionnaire including the General Health Questionnaire (GHQ) 12-item version, sociodemographic, and lifestyle factors. Associations between the GHQ scores and other variables were examined using two-way analysis of variance (ANOVA) followed by multiple comparisons and logistic regression stratified by age and gender. RESULTS: Multiple comparisons indicated that people aged 20-39 or 40-64 had higher GHQ scores than older aged. The two-way ANOVA revealed significant interaction between body mass index and age group, and between exercise and age group. Overweight or underweight males aged 40-64 had poorer mental health than those at normal weight. In the elderly, being underweight was significantly associated with poor mental health. There were no significant effects of exercise on mental health for young adults. The logistic regression showed significant negative effects of short-time sleep in adults. CONCLUSIONS: The associations between mental health and lifestyles differ across age groups. Further study is needed to reveal effects of aging on lifestyle and mental health with a longitudinal design. PMID- 27270414 TI - The unconventional secretion of ARMS2. AB - Age-related maculopathy susceptibility 2 (ARMS2) is a small (11 kDa), primate specific protein found in the extracellular matrix of the choroid layer in the eye. Variants in the corresponding genetic locus are highly associated with age related macular degeneration, a leading cause of blindness in the elderly. So far, the physiological function of ARMS2 has remained enigmatic. It has been demonstrated that ARMS2 is a genuine secreted protein devoid of an N-terminal leader sequence, yet the mechanism how it exits the cells and enters the choroidal matrix is not understood. Here, we show that ARMS2 efficiently recruits lectin chaperones from the cytosol and colocalizes with calnexin-positive and protein disulfide isomerase-negative vesicle-like structures. Site-directed mutagenesis revealed critical elements for this interaction. Mutant forms proving unable to interact with the calnexin/calreticulin system failed secretion. On the other hand, blocking the endoplasmic reticulum to Golgi transport with brefeldin A had no effect on ARMS2 secretion. As we found ARMS2 colocalizing with GRASP65, a marker for unconventional protein secretion, autophagic factors are likely to be key in its export. Interleukin-1beta (IL-1beta) is the most established example of secretory autophagy. Co-expression experiments, however, suggest that the transport of ARMS2 is different from that of IL-1beta. In conclusion, in this work we show that ARMS2 is externalized via an unconventional pathway bypassing Golgi. Its intracellular separation from the classical secretion pathway suggests that the maturation of the protein requires a specific biochemical niche and/or may be needed to impede the premature formation of unwanted protein-protein interactions. PMID- 27270416 TI - Determination of Arbutin in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study After Oral Administration of the Extract of Vaccinium vitis-idaea. AB - A rapid and sensitive bioassay based on liquid chromatography-tandem mass spectrometry (LC-MS-MS) has been developed and validated to measure arbutin in rat plasma. Sample preparation of plasma after the addition of indapamide as internal standard (IS) involved solid-phase extraction (SPE) on C18 cartridges. Reversed-phase chromatography using acetonitrile and 0.5% formic acid solution (pH 2.56) was used for separation in a run time of 4.0 min. The analytes were detected in the negative ion mode using selective reaction monitoring (SRM) of the transitions at m/z 271.2 -> 107.8 for arbutin and 364.3 -> 189.0 for indapamide. The method has the following performance characteristics: a reliable response range of 7.5-5250.0 ng/mL with correlation coefficients (r) of >0.995. The lower limit of quantitation (LLOQ) was 7.5 ng/mL. The intra- and inter-day precision and accuracy of the quality control (QC) samples at low, medium and high concentration levels showed <=8.79% relative standard deviation (RSD) and 1.15 to 1.49% relative error (RE). The method was successfully applied to a pharmacokinetic study to measure arbutin in rats after extracts of Vaccinium vitis-idaea was orally administered. PMID- 27270417 TI - Development and Validation of a New Stability-Indicating RP-UPLC Method for the Quantitative Determination of Bromfenac Sodium and Its Impurities in an Ophthalmic Dosage Form. AB - A new rapid stability-indicating reversed-phase UPLC method was developed and validated for the determination of Bromfenac sodium and its impurities in Bromfenac ophthalmic solution. During literature search, only a few publications were found about Bromfenac sodium. There is no official monograph in the pharmacopoeias about Bromfenac sodium. Chromatographic separation has been achieved on a polar-embedded Waters Acquity BEH Shield RP18 (100 mm * 2.1 mm, 1.7 MUm) column under gradient elution by using a binary mixture of potassium dihydrogen phosphate (0.01 M, pH 3.3) and acetonitrile (ACN) at a flow rate of 0.5 mL/min. Chromatogram was monitored at 265 nm using a photodiode array detector (PDA). The drug and its related impurities are eluted within 13 min. Resolution of Bromfenac sodium and all eight potential impurities have been achieved greater than 4.0 for all pairs of compounds. To prove the stability indicating power of the method, the drug was subjected to hydrolytic (acid, alkaline and water), oxidative, photolytic and thermal stress, and the major degradation products were identified based on LC-MS analysis. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, precision, accuracy and robustness. PMID- 27270415 TI - Neuronal deficiency of ARV1 causes an autosomal recessive epileptic encephalopathy. AB - We report an individual who presented with severe neurodevelopmental delay and an intractable infantile-onset seizure disorder. Exome sequencing identified a homozygous single nucleotide change that abolishes a splice donor site in the ARV1 gene (c.294 + 1G > A homozygous). This variant completely prevented splicing in minigene assays, and resulted in exon skipping and an in-frame deletion of 40 amino acids in primary human fibroblasts (NP_073623.1: p.(Lys59_Asn98del). The p.(Lys59_Asn98del) and previously reported p.(Gly189Arg) ARV1 variants were evaluated for protein expression and function. The p.(Gly189Arg) variant partially rescued the temperature-dependent growth defect in arv1Delta yeast, while p.(Lys59-Asn98del) completely failed to rescue at restrictive temperature. In contrast to wild type human ARV1, neither variant expressed detectable levels of protein in mammalian cells. Mice with a neuronal deletion of Arv1 recapitulated the human phenotype, exhibiting seizures and a severe survival defect in adulthood. Our data support ARV1 deficiency as a cause of autosomal recessive epileptic encephalopathy. PMID- 27270418 TI - General medium for the autotrophic cultivation of acetogens. AB - Syngas fermentation, a microbial process in which synthesis gas serves as a substrate for acetogens, has attracted increasing interest in the last few years. For the purposeful selection of acetogens for various applications, it would be useful to characterize and compare the process performances of as many autotrophic strains as possible under identical process conditions. Unfortunately, all the media compositions so far recommended for syngas fermentation differ considerably with respect to each individual strain. Therefore, a general medium for syngas fermentation was designed. The suitability of this new general-acetogen medium (GA-medium) was proven based on the autotrophic batch cultivation of Acetobacterium fimetarium, Acetobacterium wieringae, Blautia hydrogenotrophica, Clostridium magnum, Eubacterium aggregans, Sporomusa acidovorans, Sporomusa ovata and Terrisporobacter mayombei in anaerobic flasks with an initial gas phase of H2:CO2 (66:34) (P = 200 kPa). A comparison of the autotrophic batch processes with this medium revealed T. mayombei as the bacterium with the highest maximum growth rate of 5.77 day(-1) which was more than 10 times higher than the lowest identified maximum growth rate of A. fimetarium. The maximum growth rates of A. wieringae, C. magnum and S. acidovorans were all in the same order of magnitude around 1.7 day(-1). The newly designed GA-medium offers the possibility to compare autotrophic process performances of different acetogens under similar conditions absent the effects of various media compositions. PMID- 27270419 TI - "Don't eat so much:" how parent comments relate to female weight satisfaction. AB - PURPOSE: How will the words of a parent influence the adult weight of their daughter? This retrospective study evaluates how the recalled comments of parents made about the weight or eating habits of a daughter related to her adult BMI and satisfaction with her weight. METHOD: A nationwide cross-sectional survey was conducted with 501 young women ranging in age from 20 to 35 (age 26.8, SD 3.1; BMI 25.96, SD 6.2), who were asked to indicate their weight satisfaction, eating habits, and BMI along with their recall of the extent to which they recalled their parents making weight-related or eating-related comments about them as a young girl. Linear regression analyses were run to examine the relationship between parental comments and women's weight satisfaction and BMI. RESULTS: A woman's dissatisfaction with her adult weight was only related to the extent she remembered her parents making any comments about her weight (p < 0.01), but not about how much she ate (p < 0.05)-even though both were positively related to her BMI (p < 0.001 and p < 0.01). Even among normal-weight young women with similar weights, those who recalled their parents commenting about their weight were more dissatisfied with their body weight (p < 0.01). DISCUSSION: In this retrospective study, a parent's comments about her childhood weight were related to her weight and body dissatisfaction as an adult. In contrast, comments about her eating habits were not significantly related to weight dissatisfaction. PMID- 27270420 TI - Prognostic Factors and Multidisciplinary Postoperative Chemoradiotherapy for Clinical T4a Tongue Cancer. AB - OBJECTIVE: The prognosis of patients with locally advanced squamous cell carcinoma (SCC) of the tongue is poor. Postoperative chemoradiotherapy (CRT) improves locoregional control and survival in high-risk patients. We investigated the prognostic factors for clinical T4a tongue SCC, and elucidated whether postoperative CRT has a benefit for patients with poor prognosis in terms of survival. METHODS: We performed a retrospective analysis of 61 patients with stage T4a SCC of the tongue who underwent primary resection and neck dissection. RESULTS: The median follow-up was 53.8 months. Multivariate analysis revealed a 4.26* relative risk of death for patients with the involvement of >=5 regional lymph nodes (pN >=5) compared with those with pN 0-4 (p = 0.002). In Kaplan-Meier analysis, patients with pN >=5 who received CRT had longer overall survival rates than those who did not (hazard ratio = 0.31; p = 0.041). CONCLUSIONS: pN >=5 is the most powerful prognostic factor for clinical T4a SCC of the tongue. Postoperative CRT is recommended in patients with pN >=5. PMID- 27270421 TI - Integrated genomic analysis of colorectal cancer progression reveals activation of EGFR through demethylation of the EREG promoter. AB - Key molecular drivers that underlie transformation of colonic epithelium into colorectal adenocarcinoma (CRC) are well described. However, the mechanisms through which clinically targeted pathways are activated during CRC progression have yet to be elucidated. Here, we used an integrative genomics approach to examine CRC progression. We used laser capture microdissection to isolate colonic crypt cells, differentiated surface epithelium, adenomas, carcinomas and metastases, and used gene expression profiling to identify pathways that were differentially expressed between the different cell types. We identified a number of potentially important transcriptional changes in developmental and oncogenic pathways, and noted a marked upregulation of EREG in primary and metastatic cancer cells. We confirmed this pattern of gene expression by in situ hybridization and observed staining consistent with autocrine expression in the tumor cells. Upregulation of EREG during the adenoma-carcinoma transition was associated with demethylation of two key sites within its promoter, and this was accompanied by an increase in the levels of epidermal growth factor receptor (EGFR) phosphorylation, as assessed by reverse-phase protein analysis. In CRC cell lines, we demonstrated that EREG demethylation led to its transcriptional upregulation, higher levels of EGFR phosphorylation, and sensitization to EGFR inhibitors. Low levels of EREG methylation in patients who received cetuximab as part of a phase II study were associated with high expression of the ligand and a favorable response to therapy. Conversely, high levels of promoter methylation and low levels of EREG expression were observed in tumors that progressed after treatment. We also noted an inverse correlation between EREG methylation and expression levels in several other cancers, including those of the head and neck, lung and bladder. Therefore, we propose that upregulation of EREG expression through promoter demethylation might be an important means of activating the EGFR pathway during the genesis of CRC and potentially other cancers. PMID- 27270422 TI - MiR-26a inhibits stem cell-like phenotype and tumor growth of osteosarcoma by targeting Jagged1. AB - MicroRNAs (miRNAs) are important epigenetic regulators of gene expression. Although several miRNAs have been implicated in osteosarcoma, their role in regulation of osteosarcoma cancer stem cells (CSCs) remains unknown. Here we demonstrated that miR-26a is downregulated in osteosarcoma CSCs when derived by either sarcosphere generation, chemodrug or aldehyde dehydrogenase (ALDH) activity selection. Lentiviral overexpression of miR-26a in ZOS and 143B osteosarcoma cells decreases the expression of stem cell markers and suppresses sarcosphere formation, as well as ALDH activity. Moreover, miR-26a overexpression inhibits the tumor cell growth both in vitro and in vivo. We further demonstrate that miR-26a directly target Jagged1, one of the Notch ligand, and that its tumor suppressive effects are mediated through inhibition of Jagged1/Notch signaling. Importantly, reduced miR-26a expression, as determined by in situ hybridization in patient tumors (n=92), is associated with lung metastasis and poor overall survival of osteosarcoma patients. Together, these data suggest the essential role of miR-26a/Jagged1/Notch pathway in regulating the stem cell-like traits of osteosarcoma cells and provide a potential target for osteosarcoma therapy. PMID- 27270423 TI - miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop modulated by PDCD4 suppresses cell growth, metastasis, and sensitizes nasopharyngeal carcinoma to cisplatin. AB - miR-374a has been reported to function as an oncogene during tumor pathogenesis. In this study, miR-374a is observed to reduce nasopharyngeal carcinoma (NPC) cell proliferation, migration, invasion, metastasis and cisplatin (DDP) resistance in vitro and in vivo. Mechanistic analyses indicate that miR-374a directly targets CCND1 to inactivate pPI3K/pAKT/c-JUN forming a negative feedback loop, as well as suppressing downstream signals related to cell cycle progression and epithelial mesenchymal transition (EMT). Interestingly, we also observed that miR-374a direct targeting of CCND1 is modulated by tumor suppressor PDCD4 via suppressing pPI3K/pAKT/c-JUN signaling. In clinical specimens, miR-374a was positively and negatively correlated with expression of PDCD4 and CCND1, respectively. Our studies are the first to demonstrate that the miR-374a-CCND1-pPI3K/AKT-c-JUN feedback loop induced by PDCD4 supresses NPC cell growth, metastasis and chemotherapy resistance. PMID- 27270425 TI - SENP1-modulated sumoylation regulates retinoblastoma protein (RB) and Lamin A/C interaction and stabilization. AB - The retinoblastoma tumor suppressor protein (RB) plays a critical role in cell proliferation and differentiation and its inactivation is a frequent underlying factor in tumorigenesis. While the regulation of RB function by phosphorylation is well studied, proteasome-mediated RB protein degradation is emerging as an important regulatory mechanism. Although our understanding of RB turnover is currently limited, there is evidence that the nuclear lamina filament protein Lamin A/C protects RB from proteasomal degradation. Here we show that SUMO1 conjugation of RB and Lamin A/C is modulated by the SUMO protease SENP1 and that sumoylation of both proteins is required for their interaction. Importantly, this SUMO1-dependent complex protects both RB and Lamin A/C from proteasomal turnover. PMID- 27270424 TI - The FEN1 L209P mutation interferes with long-patch base excision repair and induces cellular transformation. AB - Flap endonuclease-1 (FEN1) is a multifunctional, structure-specific nuclease that has a critical role in maintaining human genome stability. FEN1 mutations have been detected in human cancer specimens and have been suggested to cause genomic instability and cancer predisposition. However, the exact relationship between FEN1 deficiency and cancer susceptibility remains unclear. In the current work, we report a novel colorectal cancer-associated FEN1 mutation, L209P. This mutant protein lacks the FEN, exonuclease (EXO) and gap endonuclease (GEN) activities of FEN1 but retains DNA-binding affinity. The L209P FEN1 variant interferes with the function of the wild-type FEN1 enzyme in a dominant-negative manner and impairs long-patch base excision repair in vitro and in vivo. Expression of L209P FEN1 sensitizes cells to DNA damage, resulting in endogenous genomic instability and cellular transformation, as well as tumor growth in a mouse xenograft model. These data indicate that human cancer-associated genetic alterations in the FEN1 gene can contribute substantially to cancer development. PMID- 27270426 TI - The ERK-ZEB1 pathway mediates epithelial-mesenchymal transition in pemetrexed resistant lung cancer cells with suppression by vinca alkaloids. AB - High thymidylate synthase (TS) level in cancer tissue is considered to result in resistance to pemetrexed therapy for advanced stages of nonsquamous non-small cell lung cancers. To further investigate the mechanism of pemetrexed resistance and potential prognostic outcomes in lung cancer, we established pemetrexed resistant lung adenocarcinoma cell sublines from CL1 harboring a mutated TP53 gene (R248W) and A549 harboring wild-type TP53. We found the TS expression is upregulated in both pemetrexed-resistant sublines and the reduced TS level achieved through shRNA inhibition resulted in higher pemetrexed sensitivity. We also demonstrated that the acquisitions of pemetrexed resistance enhances epithelial-mesenchymal transition (EMT) in vivo with a mice animal model and in vitro with CL1 and A549 sublines, which was associated with upregulation of ZEB1 which, in turn, downregulates E-cadherin and upregulates fibronectin. When ERK1/2 phosphorylation was reduced by an inhibitor (U0126) or siRNA inhibition, both pemetrexed-resistant sublines reduced their migration and invasion abilities. Therefore, the ERK-mediated pathways induce apoptosis with pemetrexed treatment, and may in turn mediate EMT when cancer cells are resistant to pemetrexed. We further demonstrated that the growth of pemetrexed-resistant tumors could be inhibited by vinblastine in vivo and vincristine in vitro. Our data indicate that pemetrexed resistance could be relieved by non-cross-resistant chemotherapeutic drugs such as vinca alkaloids and might be independent to TP53 status. Furthermore, the phosphorylation of ERK was reduced by vincristine. This finding provides a new insight for overcoming pemetrexed resistance and metastasis by application of vinca alkaloids. PMID- 27270427 TI - Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-beta responses. AB - Smad proteins are central mediators in the canonical transforming growth factor beta (TGF-beta) signaling pathway in mammalian cells. We report here that bromodomain-containing protein 7 (BRD7) functions as a novel transcription coactivator for Smads in TGF-beta signaling. BRD7 forms a TGF-beta inducible complex with Smad3/4 through its N-terminal Smad-binding domain. BRD7 simultaneously binds to acetylated histones to promote Smad-chromatin association, and associates with histone acetyltransferase p300 to enhance Smad transcriptional activity. Ectopic expression of BRD7, but not its mutants defective in Smad binding, enhances TGF-beta transcriptional, tumor-suppressing and epithelial-mesenchymal transition responses. Conversely, depletion of BRD7 inhibits TGF-beta responses. Thus, our study provides compelling evidence for a new function of BRD7 in fine-tuning TGF-beta physiological responses. PMID- 27270428 TI - WNT5A: a motility-promoting factor in Hodgkin lymphoma. AB - Classical Hodgkin lymphoma (cHL) has a typical clinical manifestation, with dissemination involving functionally neighboring lymph nodes. The factors involved in the spread of lymphoma cells are poorly understood. Here we show that cHL cell lines migrate with higher rates compared with non-Hodgkin lymphoma cell lines. cHL cell migration, invasion and adhesion depend on autocrine WNT signaling as revealed by the inhibition of WNT secretion with the porcupine inhibitors Wnt-C59/IWP-2, but did not affect cell proliferation. While application of recombinant WNT5A or WNT5A overexpression stimulates HL cell migration, neither WNT10A, WNT10B nor WNT16 did so. Time-lapse studies revealed an amoeboid type of cell migration modulated by WNT5A. Reduced migration distances and velocity of cHL cells, as well as altered movement patterns, were observed using porcupine inhibitor or WNT5A antagonist. Knockdown of Frizzled5 and Dishevelled3 disrupted the WNT5A-mediated RHOA activation and cell migration. Overexpression of DVL3-K435M or inhibition of ROCK (Rho-associated protein kinase) by Y-27632/H1152P disrupted cHL cell migration. In addition to these mechanistic insights into the role of WNT5A in vitro, global gene expression data revealed an increased WNT5A expression in primary HL cells in comparison with normal B-cell subsets and other lymphomas. Furthermore, the activity of both porcupine and WNT5A in cHL cells had an impact on lymphoma development in the chick chorionallantoic membrane assay. Massive bleeding of these lymphomas was significantly reduced after inhibition of WNT secretion by Wnt-C59. Therefore, a model is proposed where WNT signaling has an important role in regulating tumor promoting processes. PMID- 27270429 TI - Targeting 6-phosphogluconate dehydrogenase in the oxidative PPP sensitizes leukemia cells to antimalarial agent dihydroartemisinin. AB - The oxidative pentose phosphate pathway (PPP) is crucial for cancer cell metabolism and tumor growth. We recently reported that targeting a key oxidative PPP enzyme, 6-phosphogluconate dehydrogenase (6PGD), using our novel small molecule 6PGD inhibitors Physcion and its derivative S3, shows anticancer effects. Notably, humans with genetic deficiency of either 6PGD or another oxidative PPP enzyme, glucose-6-phosphate dehydrogenase, exhibit non-immune hemolytic anemia upon exposure to aspirin and various antimalarial drugs. Inspired by these clinical observations, we examined the anticancer potential of combined treatment with 6PGD inhibitors and antimalarial drugs. We found that stable knockdown of 6PGD sensitizes leukemia cells to antimalarial agent dihydroartemisinin (DHA). Combined treatment with DHA and Physcion activates AMP activated protein kinase, leading to synergistic inhibition of human leukemia cell viability. Moreover, our combined therapy synergistically attenuates tumor growth in xenograft nude mice injected with human K562 leukemia cells and cell viability of primary leukemia cells from human patients, but shows minimal toxicity to normal hematopoietic cells in mice as well as red blood cells and mononucleocytes from healthy human donors. Our findings reveal the potential for combined therapy using optimized doses of Physcion and DHA as a novel antileukemia treatment without inducing hemolysis. PMID- 27270430 TI - Base changes in tumour DNA have the power to reveal the causes and evolution of cancer. AB - Next-generation sequencing (NGS) technology has demonstrated that the cancer genomes are peppered with mutations. Although most somatic tumour mutations are unlikely to have any role in the cancer process per se, the spectra of DNA sequence changes in tumour mutation catalogues have the potential to identify the mutagens, and to reveal the mutagenic processes responsible for human cancer. Very recently, a novel approach for data mining of the vast compilations of tumour NGS data succeeded in separating and precisely defining at least 30 distinct patterns of sequence change hidden in mutation databases. At least half of these mutational signatures can be readily assigned to known human carcinogenic exposures or endogenous mechanisms of mutagenesis. A quantum leap in our knowledge of mutagenesis in human cancers has resulted, stimulating a flurry of research activity. We trace here the major findings leading first to the hypothesis that carcinogenic insults leave characteristic imprints on the DNA sequence of tumours, and culminating in empirical evidence from NGS data that well-defined carcinogen mutational signatures are indeed present in tumour genomic DNA from a variety of cancer types. The notion that tumour DNAs can divulge environmental sources of mutation is now a well-accepted fact. This approach to cancer aetiology has also incriminated various endogenous, enzyme driven processes that increase the somatic mutation load in sporadic cancers. The tasks now confronting the field of molecular epidemiology are to assign mutagenic processes to orphan and newly discovered tumour mutation patterns, and to determine whether avoidable cancer risk factors influence signatures produced by endogenous enzymatic mechanisms. Innovative research with experimental models and exploitation of the geographical heterogeneity in cancer incidence can address these challenges. PMID- 27270431 TI - Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma. AB - As a transcription factor, localization to the nucleus and the recruitment of cofactors to regulate gene transcription is essential. Nuclear localization and nucleosome remodeling and histone deacetylase (NuRD) complex binding are required for the zinc-finger transcription factor CASZ1 to function as a neuroblastoma (NB) tumor suppressor. However, the critical amino acids (AAs) that are required for CASZ1 interaction with NuRD complex and the regulation of CASZ1 subcellular localization have not been characterized. Through alanine scanning, immunofluorescence cell staining and co-immunoprecipitation, we define a critical region at the CASZ1 N terminus (AAs 23-40) that mediates the CASZ1b nuclear localization and NuRD interaction. Furthermore, we identified a nuclear export signal (NES) at the N terminus (AAs 176-192) that contributes to CASZ1 nuclear cytoplasmic shuttling in a chromosomal maintenance 1-dependent manner. An analysis of CASZ1 protein expression in a primary NB tissue microarray shows that high nuclear CASZ1 staining is detected in tumor samples from NB patients with good prognosis. In contrast, cytoplasmic-restricted CASZ1 staining or low nuclear CASZ1 staining is found in tumor samples from patients with poor prognosis. These findings provide insight into mechanisms by which CASZ1 regulates transcription, and suggests that regulation of CASZ1 subcellular localization may impact its function in normal development and pathologic conditions such as NB tumorigenesis. PMID- 27270432 TI - VEGF-ablation therapy reduces drug delivery and therapeutic response in ECM-dense tumors. AB - The inadequate transport of drugs into the tumor tissue caused by its abnormal vasculature is a major obstacle to the treatment of cancer. Anti-vascular endothelial growth factor (anti-VEGF) drugs can cause phenotypic alteration and maturation of the tumor's vasculature. However, whether this consistently improves delivery and subsequent response to therapy is still controversial. Clinical results indicate that not all patients benefit from antiangiogenic treatment, necessitating the development of criteria to predict the effect of these agents in individual tumors. We demonstrate that, in anti-VEGF-refractory murine tumors, vascular changes after VEGF ablation result in reduced delivery leading to therapeutic failure. In these tumors, the impaired response after anti VEGF treatment is directly linked to strong deposition of fibrillar extracellular matrix (ECM) components and high expression of lysyl oxidases. The resulting condensed, highly crosslinked ECM impeded drug permeation, protecting tumor cells from exposure to small-molecule drugs. The reduced vascular density after anti VEGF treatment further decreased delivery in these tumors, an effect not compensated by the improved vessel quality. Pharmacological inhibition of lysyl oxidases improved drug delivery in various tumor models and reversed the negative effect of VEGF ablation on drug delivery and therapeutic response in anti-VEGF resistant tumors. In conclusion, the vascular changes after anti-VEGF therapy can have a context-dependent negative impact on overall therapeutic efficacy. A determining factor is the tumor ECM, which strongly influences the effect of anti VEGF therapy. Our results reveal the prospect to revert a possible negative effect and to potentiate responsiveness to antiangiogenic therapy by concomitantly targeting ECM-modifying enzymes. PMID- 27270433 TI - A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer. AB - MicroRNA-375 (miR-375) is frequently elevated in prostate tumors and cell-free fractions of patient blood, but its role in genesis and progression of prostate cancer is poorly understood. In this study, we demonstrated that miR-375 is inversely correlated with epithelial-mesenchymal transition signatures (EMT) in clinical samples and can drive mesenchymal-epithelial transition (MET) in model systems. Indeed, miR-375 potently inhibited invasion and migration of multiple prostate cancer lines. The transcription factor YAP1 was found to be a direct target of miR-375 in prostate cancer. Knockdown of YAP1 phenocopied miR-375 overexpression, and overexpression of YAP1 rescued anti-invasive effects mediated by miR-375. Furthermore, transcription of the miR-375 gene was shown to be directly repressed by the EMT transcription factor, ZEB1. Analysis of multiple patient cohorts provided evidence for this ZEB1-miR-375-YAP1 regulatory circuit in clinical samples. Despite its anti-invasive and anti-EMT capacities, plasma miR-375 was found to be correlated with circulating tumor cells in men with metastatic disease. Collectively, this study provides new insight into the function of miR-375 in prostate cancer, and more broadly identifies a novel pathway controlling epithelial plasticity and tumor cell invasion in this disease. PMID- 27270434 TI - Metabolic rewiring in melanoma. AB - Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate. Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring. However, tissue of origin as well as specific genetic and epigenetic changes determines gene expression profiles underlying these metabolic alterations in specific cancers. In melanoma, activation of the mitogen-activated protein kinase (MAPK) pathway driven by mutant BRAF or NRAS is a primary cause of malignant transformation. Activity of the MAPK pathway, as well as other factors, such as HIF1alpha, Myc and MITF, are among those that control the balance between non-oxidative and oxidative branches of central carbon metabolism. Here, we discuss the nature of metabolic alterations that underlie melanoma development and affect its response to therapy. PMID- 27270435 TI - Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary. AB - R-spondin1 is a secreted regulator of WNT signaling, involved in both embryonic development and homeostasis of adult organs. It can have a dual role, acting either as a mitogen or as a tumor suppressor. During ovarian development, Rspo1 is a key factor required for sex determination and differentiation of the follicular cell progenitors, but is downregulated after birth. In human, increased RSPO1 expression is associated with ovarian carcinomas, but it is not clear whether it is a cause or a consequence of the tumorigenic process. To address the role of Rspo1 expression in adult ovaries, we generated an Rspo1 gain of-function mouse model. Females were hypofertile and exhibited various ovarian defects, ranging from cysts to ovarian tumors. Detailed phenotypical characterization showed anomalies in the ovulation process. Although follicles responded to initial follicle-stimulating hormone stimulation and developed normally until the pre-ovulatory stage, they did not progress any further. Although non-ovulated oocytes degenerated, the surrounding follicular cells did not begin atresia. RSPO1-induced expression not only promotes canonical WNT signaling but also alters granulosa cell fate decisions by maintaining epithelial like traits in these cells. This prevents follicle cells from undergoing apoptosis, leading to the accumulation of granulosa cell tumors that reactivates the epithelial program from their progenitors. Taken together, our data demonstrate that activation of RSPO1 is sufficient in promoting ovarian tumors and thus supports a direct involvement of this gene in the commencement of ovarian cancers. PMID- 27270436 TI - Targeting Oct1 genomic function inhibits androgen receptor signaling and castration-resistant prostate cancer growth. AB - Androgen receptor (AR) functions as a ligand-dependent transcription factor to regulate its downstream signaling for prostate cancer progression. AR complex formation by multiple transcription factors is important for enhancer activity and transcriptional regulation. However, the significance of such collaborative transcription factors has not been fully understood. In this study, we show that Oct1, an AR collaborative factor, coordinates genome-wide AR signaling for prostate cancer growth. Using global analysis by chromatin immunoprecipitation sequencing (ChIP-seq), we found that Oct1 is recruited to AR-binding enhancer/promoter regions and facilitates androgen signaling. Moreover, a major target of AR/Oct1 complex, acyl-CoA synthetase 3 (ACSL3), contributes to tumor growth in nude mice, and its high expression is associated with poor prognosis in prostate cancer patients. Next, we examined the therapeutic effects of pyrrole imidazole polyamides that target the Oct1-binding sequence identified in the center of the ACSL3 AR-binding site. We observed that treatment with Oct1 polyamide severely blocked the Oct1 binding at the ACSL3 enhancer responsible for its transcriptional activity and ACSL3 induction. In addition, Oct1 polyamides suppressed castration-resistant tumor growth and specifically repressed global Oct1 chromatin association and androgen signaling in prostate cancer cells, with few nonspecific effects on basal promoter activity. Thus, targeting Oct1 binding could be a novel therapeutic strategy for AR-activated castration-resistant prostate cancer. PMID- 27270438 TI - p27Kip1 represses the Pitx2-mediated expression of p21Cip1 and regulates DNA replication during cell cycle progression. AB - The tumor suppressor p21 regulates cell cycle progression and peaks at mid/late G1. However, the mechanisms regulating its expression during cell cycle are poorly understood. We found that embryonic fibroblasts from p27 null mice at early passages progress slowly through the cell cycle. These cells present an elevated basal expression of p21 suggesting that p27 participates to its repression. Mechanistically, we found that p27 represses the expression of Pitx2 (an activator of p21 expression) by associating with the ASE-regulatory region of this gene together with an E2F4 repressive complex. Furthermore, we found that Pitx2 binds to the p21 promoter and induces its transcription. Finally, silencing Pitx2 or p21 in proliferating cells accelerates DNA replication and cell cycle progression. Collectively, these results demonstrate an unprecedented connection between p27, Pitx2 and p21 relevant for the regulation of cell cycle progression and cancer and for understanding human pathologies associated with p27 germline mutations. PMID- 27270437 TI - Myeloid translocation genes differentially regulate colorectal cancer programs. AB - Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1-/- mice have progressive depletion of all intestinal secretory cells, and Mtg16-/- mice have a decrease in goblet cells. Furthermore, both Mtgr1-/- and Mtg16-/- mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1-/- mice, but not Mtg16-/- mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of chromatin immunoprecipitation sequencing data sets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1-/- tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context-dependent effect on intestinal tumorigenesis. PMID- 27270439 TI - Lysine demethylase KDM3A regulates breast cancer cell invasion and apoptosis by targeting histone and the non-histone protein p53. AB - Invasive growth and apoptosis resistance of breast cancer cells are associated with metastasis and disease relapse. Here we identified that the lysine-specific demethylase KDM3A played a dual role in breast cancer cell invasion and apoptosis by demethylating histone and the non-histone protein p53, respectively. While inducing pro-invasive genes by erasing repressive histone H3 lysine 9 methylation, KDM3A promotes chemoresistance by demethylating p53. KDM3A suppressed pro-apoptotic functions of p53 by erasing p53-K372me1, as this methylation is crucial for the stability of chromatin-bound p53. Unexpectedly, depletion of KDM3A was capable of reactivating mutated p53 to induce the expression of pro-apoptotic genes in breast cancer with mutant p53. Moreover, KDM3A knockdown also potently inhibited tumorigenic potentials of breast cancer stem-like cells and rendered them sensitive to apoptosis induced by chemotherapeutic drugs. Taken together, our results suggest that KDM3A might be a potential therapeutic target for human breast cancer treatment and prevention. PMID- 27270440 TI - A TGFbeta-PRMT5-MEP50 axis regulates cancer cell invasion through histone H3 and H4 arginine methylation coupled transcriptional activation and repression. AB - Protein arginine methyltransferase 5 (PRMT5) complexed with MEP50/WDR77 catalyzes arginine methylation on histones and other proteins. PRMT5-MEP50 activity is elevated in cancer cells and its expression is highly correlated with poor prognosis in many human tumors. We demonstrate that PRMT5-MEP50 is essential for transcriptional regulation promoting cancer cell invasive phenotypes in lung adenocarcinoma, lung squamous cell carcinoma and breast carcinoma cancer cells. RNA-Seq transcriptome analysis demonstrated that PRMT5 and MEP50 are required to maintain expression of metastasis and Epithelial-to-mesenchymal transition (EMT) markers and to potentiate an epigenetic mechanism of the TGFbeta response. We show that PRMT5-MEP50 activity both positively and negatively regulates expression of a wide range of genes. Exogenous TGFbeta promotes EMT in a unique pathway of PRMT5-MEP50 catalyzed histone mono- and dimethylation of chromatin at key metastasis suppressor and EMT genes, defining a new mechanism regulating cancer invasivity. PRMT5 methylation of histone H3R2me1 induced transcriptional activation by recruitment of WDR5 and concomitant H3K4 methylation at targeted genes. In parallel, PRMT5 methylation of histone H4R3me2s suppressed transcription at distinct genomic loci. Our decoding of histone methylarginine at key genes supports a critical role for complementary PRMT5-MEP50 transcriptional activation and repression in cancer invasion pathways and in response to TGFbeta stimulation and therefore orients future chemotherapeutic opportunities. PMID- 27270441 TI - Molecular analysis of urothelial cancer cell lines for modeling tumor biology and drug response. AB - The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes. Non-silent sequence alterations were confirmed in 76 cancer-associated genes, including mutations that likely activate oncogenes TERT and PIK3CA, and alter chromatin-associated proteins (MLL3, ARID1A, CHD6 and KDM6A) and established BCa genes (TP53, RB1, CDKN2A and TSC1). We identified alterations in signaling pathways and proteins with related functions, including the PI3K/mTOR pathway, altered in 60% of lines; BRCA DNA repair, 44%; and SYNE1-SYNE2, 60%. Homozygous deletions of chromosome 9p21 are known to target the cell cycle regulators CDKN2A and CDKN2B. This loci was commonly lost in BCa cell lines and we show the deletions extended to the polyamine enzyme methylthioadenosine (MTA) phosphorylase (MTAP) in 36% of lines, transcription factor DMRTA1 (27%) and antiviral interferon epsilon (IFNE, 19%). Overall, the BCa cell line genomic aberrations were concordant with those found in BCa patient tumors. We used gene expression and copy number data to infer pathway activities for cell lines, then used the inferred pathway activities to build a predictive model of cisplatin response. When applied to platinum-treated patients gathered from TCGA, the model predicted treatment-specific response. Together, these data and analysis represent a valuable community resource to model basic tumor biology and to study the pharmacogenomics of BCa. PMID- 27270443 TI - HEMO Revisited: Why Kt/Vurea Only Tells Part of the Story. PMID- 27270444 TI - Intra-cage dynamics of molecular hydrogen confined in cages of two different dimensions of clathrate hydrates. AB - In porous materials the molecular confinement is often realized by means of weak Van der Waals interactions between the molecule and the pore surface. The understanding of the mechanism of such interactions is important for a number of applications. In order to establish the role of the confinement size we have studied the microscopic dynamics of molecular hydrogen stored in the nanocages of clathrate hydrates of two different dimensions. We have found that by varying the size of the pore the diffusive mobility of confined hydrogen can be modified in both directions, i.e. reduced or enhanced compared to that in the bulk solid at the same temperatures. In the small cages with a mean crystallographic radius of 3.95 A the confinement reduces diffusive mobility by orders of magnitude. In contrast, in large cages with a mean radius of 4.75 A hydrogen molecules displays diffusive jump motion between different equilibrium sites inside the cages, visible at temperatures where bulk H2 is solid. The localization of H2 molecules observed in small cages can promote improved functional properties valuable for hydrogen storage applications. PMID- 27270442 TI - MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer. AB - MicroRNA-101, a tumor suppressor microRNA (miR), is often downregulated in cancer and is known to target multiple oncogenes. Some of the genes that are negatively regulated by miR-101 expression include histone methyltransferase EZH2 (enhancer of zeste homolog 2), COX2 (cyclooxygenase-2), POMP (proteasome maturation protein), CERS6, STMN1, MCL-1 and ROCK2, among others. In the present study, we show that miR-101 targets transcriptional coactivator SUB1 homolog (Saccharomyces cerevisiae)/PC4 (positive cofactor 4) and regulates its expression. SUB1 is known to have diverse role in vital cell processes such as DNA replication, repair and heterochromatinization. SUB1 is known to modulate transcription and acts as a mediator between the upstream activators and general transcription machinery. Expression profiling in several cancers revealed SUB1 overexpression, suggesting a potential role in tumorigenesis. However, detailed regulation and function of SUB1 has not been elucidated. In this study, we show elevated expression of SUB1 in aggressive prostate cancer. Knockdown of SUB1 in prostate cancer cells resulted in reduced cell proliferation, invasion and migration in vitro, and tumor growth and metastasis in vivo. Gene expression analyses coupled with chromatin immunoprecipitation revealed that SUB1 binds to the promoter regions of several oncogenes such as PLK1 (Polo-like kinase 1), C-MYC, serine-threonine kinase BUB1B and regulates their expression. Additionally, we observed SUB1 downregulated CDKN1B expression. PLK1 knockdown or use of PLK1 inhibitor can mitigate oncogenic function of SUB1 in benign prostate cancer cells. Thus, our study suggests that miR-101 loss results in increased SUB1 expression and subsequent activation of known oncogenes driving prostate cancer progression and metastasis. This study therefore demonstrates functional role of SUB1 in prostate cancer, and identifies its regulation and potential downstream therapeutic targets of SUB1 in prostate cancer. PMID- 27270445 TI - Shifts in Aboveground Biomass Allocation Patterns of Dominant Shrub Species across a Strong Environmental Gradient. AB - Most plant biomass allocation studies have focused on allocation to shoots versus roots, and little is known about drivers of allocation for aboveground plant organs. We explored the drivers of within-and between-species variation of aboveground biomass allocation across a strong environmental resource gradient, i.e., a long-term chronosequence of 30 forested islands in northern Sweden across which soil fertility and plant productivity declines while light availability increases. For each of the three coexisting dominant understory dwarf shrub species on each island, we estimated the fraction of the total aboveground biomass produced year of sampling that was allocated to sexual reproduction (i.e., fruits), leaves and stems for each of two growing seasons, to determine how biomass allocation responded to the chronosequence at both the within-species and whole community levels. Against expectations, within-species allocation to fruits was least on less fertile islands, and allocation to leaves at the whole community level was greatest on intermediate islands. Consistent with expectations, different coexisting species showed contrasting allocation patterns, with the species that was best adapted for more fertile conditions allocating the most to vegetative organs, and with its allocation pattern showing the strongest response to the gradient. Our study suggests that co-existing dominant plant species can display highly contrasting biomass allocations to different aboveground organs within and across species in response to limiting environmental resources within the same plant community. Such knowledge is important for understanding how community assembly, trait spectra, and ecological processes driven by the plant community vary across environmental gradients and among contrasting ecosystems. PMID- 27270447 TI - Role of trap-induced scales in non-equilibrium dynamics of strongly interacting trapped bosons. AB - We use a time-dependent hopping expansion technique to study the non-equilibrium dynamics of strongly interacting bosons in an optical lattice in the presence of a harmonic trap characterized by a force constant K. We show that after a sudden quench of the hopping amplitude J across the superfluid (SF)-Mott insulator (MI) transition, the SF order parameter [Formula: see text] and the local density fluctuation [Formula: see text] exhibit sudden decoherence beyond a trap-induced time scale [Formula: see text]. We also show that after a slow linear ramp down of J, [Formula: see text] and the boson defect density [Formula: see text] display a novel non-monotonic spatial profile. Both these phenomena can be explained as consequences of trap-induced time and length scales affecting the dynamics and can be tested by concrete experiments. PMID- 27270446 TI - Cl- channels in apoptosis. AB - A remarkable feature of apoptosis is the initial massive cell shrinkage, which requires opening of ion channels to allow release of K+, Cl-, and organic osmolytes to drive osmotic water movement and cell shrinkage. This article focuses on the role of the Cl- channels LRRC8, TMEM16/anoctamin, and cystic fibrosis transmembrane conductance regulator (CFTR) in cellular apoptosis. LRRC8A E has been identified as a volume-regulated anion channel expressed in many cell types. It was shown to be required for regulatory and apoptotic volume decrease (RVD, AVD) in cultured cell lines. Its presence also determines sensitivity towards cytostatic drugs such as cisplatin. Recent data point to a molecular and functional relationship of LRRC8A and anoctamins (ANOs). ANO6, 9, and 10 (TMEM16F, J, and K) augment apoptotic Cl- currents and AVD, but it remains unclear whether these anoctamins operate as Cl- channels or as regulators of other apoptotic Cl- channels, such as LRRC8. CFTR has been known for its proapoptotic effects for some time, and this effect may be based on glutathione release from the cell and increase in cytosolic reactive oxygen species (ROS). Although we find that CFTR is activated by cell swelling, it is possible that CFTR serves RVD/AVD through accumulation of ROS and activation of independent membrane channels such as ANO6. Thus activation of ANO6 will support cell shrinkage and induce additional apoptotic events, such as membrane phospholipid scrambling. PMID- 27270448 TI - Studies on the cytotoxicity of diamond nanoparticles against human cancer cells and lymphocytes. AB - Detonation nanodiamonds (DND) are a widely studied group of carbon nanomaterials. They have the ability to adsorb a variety of biomolecules and drugs onto their surfaces, and additionally their surfaces may be subjected to chemical functionalization by covalent bonds. We present a procedure for the purification and surface oxidation of diamond nanoparticles, which were then tested by spectroscopic analysis such as ATR-FTIR, Raman spectroscopy, and thermogravimetric analysis. We also examined the zeta potential of the tested material. Analysis of the cytotoxic effect of nanodiamonds against normal lymphocytes derived from human peripheral blood, the non-small cell lung cancer cell line (A549) and the human colorectal adenocarcinoma cell line (HT29) was performed using MTT colorimetric assay. Evaluation of cell viability was performed after 1-h and 24-h treatment with the tested nanoparticles applied at concentrations ranging from 1 MUg/ml to 100 MUg/ml. We found that the survival of the examined cells was strongly associated with the presence of serum proteins in the growth medium. The incubation of cells with nanodiamonds in the presence of serum did not exert a significant effect on cell survival, while the cell treatment in a serum-free medium resulted in a decrease in cell survival compared to the negative control. The role of purification and functionalization of nanodiamonds on their cytotoxicity was also demonstrated. PMID- 27270449 TI - Transition metal oxide nanoparticles are effective in inhibiting lung cancer cell survival in the hypoxic tumor microenvironment. AB - BACKGROUND: The transition metal oxide nanoparticles are in focus for their anti cancer potential. In this study we have synthesized and characterized CuO, NiO and Fe2O3 nanoparticles and, investigated their cytotoxic potential in the heterogeneous tumour microenvironment. METHODS: Nanoparticles were synthesized by aqueous precipitation method and characterized with UV-Visible spectrophotometer, Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and X-ray diffraction (XRD). Cell viability of lung cancer cells (A549) grown in normoxia (18%O2) and hypoxia (1%O2) was determined for all nanoparticles. The mechanism of cell death was assessed by nuclear morphological analysis, flow cytometry analysis and western blotting. Generation of intracellular ROS in treated cells and its contribution to cell viability was determined. RESULTS: The synthesized metal oxide nanoparticles were successfully characterized with SEM, spectroscopy and X-ray diffraction patterns. Cell viability of lung cancer cells was compromised in both normoxia and hypoxia. ROS generation was shown to contribute to cellular toxicity in CuO, but not NiO and Fe2O3. CONCLUSION: We have shown the therapeutic potential of CuO, NiO and Fe2O3 nanoparticles in non small cell lung cancer cells cultured in hypoxia, a relevant feature of solid tumors along with normoxia. The newly synthesized nanoparticles showed efficacy in both conditions. GENERAL SIGNIFICANCE: Hypoxia drives metabolic alterations and epigenetic modifications in the tumor microenvironment. By using conditions that mimic tumour microenvironment, this study expands the possibility of using metal oxide nanoparticles as a therapeutic agent for lung cancer treatment. PMID- 27270450 TI - Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. AB - Recent evidences highlighted that histone deacetylases (HDACs) can deacetylate the histone, various transcription factors and regulatory proteins, which directly or indirectly affect glucose metabolism. The present study aimed to evaluate the comparative effects of sodium butyrate (NaB) and metformin on the glucose homeostasis, insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet (HFD) and low dose streptozotocin (STZ, 35 mg/kg). NaB at the doses of 200 and 400 mg/kg twice daily as well as metformin (as a positive control) 150 mg/kg twice daily for 10 consecutive weeks were administered by i.p. and oral route, respectively. NaB treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, dyslipidemia and gluconeogenesis, which are comparable to metformin treatment. Further, NaB treatment ameliorated the micro- and macro-vesicular steatosis in liver and fat deposition in brown adipose tissue, white adipose tissue (adipocytes hypertrophy) as well as pancreatic beta-cell damage. In the present study, both NaB and metformin inhibited the diabetes-associated increased HDACs activity, thereby increased the acetylation of histone H3 in liver. The present findings demonstrated that NaB and metformin reduced insulin-resistance, dyslipidemia, fat accumulation and gluconeogenesis thereby improved the glucose homeostasis in rat. Thus, NaB might be a promising molecule for the prevention and treatment of type 2 diabetes and dyslipidemia. PMID- 27270451 TI - Sesamol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways. AB - Sesamol is a phenolic lignan found in sesame seeds (Sesamum indicum L.) and sesame oil. The anticancer effects and molecular mechanisms underlying its apoptosis-inducing effect were investigated in human lung adenocarcinoma (SK-LU 1) cells. Sesamol inhibited SK-LU-1 cell growth with an IC50 value of 2.7 mM and exhibited less toxicity toward normal Vero cells after 48 h of treatment (Selective index = 3). Apoptotic bodies-the hallmark of apoptosis-were observed in sesamol-treated SK-LU-1 cells, stained with DAPI. Sesamol increased the activity of caspase 8, 9, and 3/7, indicating that apoptotic cell death occurred through both extrinsic and intrinsic pathways. Sesamol caused the loss of mitochondrial transmembrane potential signifying intrinsic apoptosis induction. Decreasing Bid expression revealed crosstalk between the intrinsic and extrinsic apoptotic pathways; demonstrating clearly that sesamol induces apoptosis through both pathways in human lung adenocarcinoma (SK-LU-1) cells. PMID- 27270452 TI - Bromobenzene-induced lethal toxicity in mouse is prevented by pretreatment with zinc sulfate. AB - In the current study, we evaluated the protective effect of zinc (Zn) against bromobenzene (BB) -induced lethal toxicity. We used Zn because this element is known to be an inducer of metallothionein (MT), which is in turn known to serve as an endogenous scavenger of free radicals. We administered Zn (as ZnSO4) at 50 mg/kg subcutaneously once-daily for 3 successive days prior to a single intraperitoneal administration of 1.2 g/kg BB in male ddY mice. Our results showed that pretreatment with Zn completely abolished the BB-induced mortality of mice until 48 h. We also found that pretreatment of mice with Zn significantly decreased the functional marker levels and reduced the histological damage both in liver and kidney as assessed at 18 h post-BB. We also showed that pretreatment with Zn enhanced antioxidative activity, resulting in decreased lipid peroxidation in both liver and kidney. Moreover, BB-induced calcium levels were downregulated by pretreatment with Zn. In addition, Zn-induced MT was decreased in Zn + BB-treated animals, implying that MT was consumed by BB-induced radicals. These findings suggest that prophylaxis with Zn protects mice from BB-induced lethal toxicity by decreasing oxidative stress in liver and kidney, presumably by induction of MT, which scavenges radicals induced by BB exposure. PMID- 27270453 TI - Combining in vitro and in silico approaches to evaluate the multifunctional profile of rosmarinic acid from Blechnum brasiliense on targets related to neurodegeneration. AB - Natural products are important sources of chemical diversity leading to unique scaffolds that can be exploited in the discovery of new drug candidates or chemical probes. In this context, chemical and biological investigation of ferns and lycophytes occurring in Brazil is an approach adopted by our research group aiming at discovering bioactive molecules acting on neurodegeneration targets. In the present study, rosmarinic acid (RA) isolated from Blechnum brasiliense showed an in vitro multifunctional profile characterized by antioxidant effects, and monoamine oxidases (MAO-A and MAO-B) and catechol-O-methyl transferase (COMT) inhibition. RA showed antioxidant effects against hydroxyl (HO(*)) and nitric oxide (NO) radicals (IC50 of 29.4 and 140 MUM, respectively), and inhibition of lipid peroxidation (IC50 of 19.6 MUM). In addition, RA inhibited MAO-A, MAO-B and COMT enzymes with IC50 values of 50.1, 184.6 and 26.7 MUM, respectively. The MAO A modulation showed a non-time-dependent profile, suggesting a reversible mechanism of inhibition. Structural insights on RA interactions with MAO-A and COMT were investigated by molecular docking. Finally, RA (up to 5 mM) demonstrated no cytotoxicity on polymorphonuclear rat cells. Taken together, our results suggest that RA may be exploited as a template for the development of new antioxidant molecules possessing additional MAO and COMT inhibition effects to be further investigated on in vitro and in vivo models of neurodegenerative diseases. PMID- 27270454 TI - MicroRNAs related to androgen metabolism and polycystic ovary syndrome. AB - Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women. PCOS is associated with altered features of androgen metabolism, increased insulin resistance and impaired fertility. Furthermore, PCOS, being a syndrome diagnosis, is heterogeneous and characterized by polycystic ovaries, chronic anovulation and evidence of hyperandrogenism, as well as being associated with chronic low-grade inflammation and an increased life time risk of type 2 diabetes. A number of androgen species contribute to the symptoms of increased androgen exposure seen in many, though not all, cases of PCOS: Testosterone, androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), where the quantitatively highest amount of androgen is found as DHEAS. The sulfation of DHEA to DHEAS depends on a number of enzymes, and altered sulfate metabolism may be associated with and contribute to the pathogenesis of PCOS. MicroRNAs (miRNAs) are small, non-coding RNAs that are able to regulate gene expression at the post transcriptional level. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that these might serve as potential biomarkers and a new approach for the diagnosis of PCOS. In this review, recent work on miRNAs with respect to PCOS will be summarized. Our understanding of miRNAs, particularly in relation to PCOS, is currently at a very early stage, and additional studies will yield important insight into the molecular mechanisms behind this complex and heterogenic syndrome. PMID- 27270455 TI - Indirect Fitness Benefits Enable the Spread of Host Genes Promoting Costly Transfer of Beneficial Plasmids. AB - Bacterial genes that confer crucial phenotypes, such as antibiotic resistance, can spread horizontally by residing on mobile genetic elements (MGEs). Although many mobile genes provide strong benefits to their hosts, the fitness consequences of the process of transfer itself are less clear. In previous studies, transfer has been interpreted as a parasitic trait of the MGEs because of its costs to the host but also as a trait benefiting host populations through the sharing of a common gene pool. Here, we show that costly donation is an altruistic act when it spreads beneficial MGEs favoured when it increases the inclusive fitness of donor ability alleles. We show mathematically that donor ability can be selected when relatedness at the locus modulating transfer is sufficiently high between donor and recipients, ensuring high frequency of transfer between cells sharing donor alleles. We further experimentally demonstrate that either population structure or discrimination in transfer can increase relatedness to a level selecting for chromosomal transfer alleles. Both mechanisms are likely to occur in natural environments. The simple process of strong dilution can create sufficient population structure to select for donor ability. Another mechanism observed in natural isolates, discrimination in transfer, can emerge through coselection of transfer and discrimination alleles. Our work shows that horizontal gene transfer in bacteria can be promoted by bacterial hosts themselves and not only by MGEs. In the longer term, the success of cells bearing beneficial MGEs combined with biased transfer leads to an association between high donor ability, discrimination, and mobile beneficial genes. However, in conditions that do not select for altruism, host bacteria promoting transfer are outcompeted by hosts with lower transfer rate, an aspect that could be relevant in the fight against the spread of antibiotic resistance. PMID- 27270456 TI - No Evidence for Threat-Induced Spatial Prioritization of Somatosensory Stimulation during Pain Control Using a Synchrony Judgment Paradigm. AB - Topical research efforts on attention to pain often take a critical look at the modulatory role of top-down factors. For instance, it has been shown that the fearful expectation of pain at a location of the body directs attention towards that body part. In addition, motivated attempts to control this pain were found to modulate this prioritization effect. Such studies have often used a temporal order judgment task, requiring participants to judge the order in which two stimuli are presented by indicating which one they perceived first. As this constitutes a forced-choice response format, such studies may be subject to response bias. The aim of the current study was to address this concern. We used a ternary synchrony judgment paradigm, in which participants judged the order in which two somatosensory stimuli occurred. Critically, participants now also had the option to give a 'simultaneous' response when they did not perceive a difference. This way we eliminated the need for guessing, and thus reduced the risk of response bias. One location was threatened with the possibility of pain in half of the trials, as predicted by an auditory cue. Additionally, half of the participants (pain control group) were encouraged to avoid pain stimuli by executing a quick button press. The other half (comparison group) performed a similar action, albeit unrelated to the occurrence of pain. Our data did not support threat-induced spatial prioritization, nor did we find evidence that pain control attempts influenced attention in any way. PMID- 27270457 TI - ABRAXAS (FAM175A) and Breast Cancer Susceptibility: No Evidence of Association in the Breast Cancer Family Registry. AB - Approximately half of the familial aggregation of breast cancer remains unexplained. This proportion is less for early-onset disease where familial aggregation is greater, suggesting that other susceptibility genes remain to be discovered. The majority of known breast cancer susceptibility genes are involved in the DNA double-strand break repair pathway. ABRAXAS is involved in this pathway and mutations in this gene impair BRCA1 recruitment to DNA damage foci and increase cell sensitivity to ionizing radiation. Moreover, a recurrent germline mutation was reported in Finnish high-risk breast cancer families. To determine if ABRAXAS could be a breast cancer susceptibility gene in other populations, we conducted a population-based case-control mutation screening study of the coding exons and exon/intron boundaries of ABRAXAS in the Breast Cancer Family Registry. In addition to the common variant p.Asp373Asn, sixteen distinct rare variants were identified. Although no significant difference in allele frequencies between cases and controls was observed for the identified variants, two variants, p.Gly39Val and p.Thr141Ile, were shown to diminish phosphorylation of gamma-H2AX in MCF7 human breast adenocarcinoma cells, an important biomarker of DNA double-strand breaks. Overall, likely damaging or neutral variants were evenly represented among cases and controls suggesting that rare variants in ABRAXAS may explain only a small proportion of hereditary breast cancer. PMID- 27270458 TI - Flow Cytometric Quantification of Peripheral Blood Cell beta-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension. AB - Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although beta-adrenergic receptor (betaAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of betaAR density on circulating white blood cells (WBC) and Ec MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated beta-blocker alprenolol was synthesized and validated as a betaAR specific probe that was combined with immunophenotyping to quantify betaAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that betaAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell betaAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID- 27270459 TI - Trait Hostility and Acute Inflammatory Responses to Stress in the Laboratory. AB - Hostility has been associated with higher basal levels of inflammation. The present study evaluated the association of hostility with acute stress-induced changes in inflammatory activity. One hundred and ninety-nine healthy men and women, aged 19-64 years, were exposed to a stress protocol involving four interpersonal stressors. Participants completed the Cook-Medley Hostility questionnaire and provided two blood samples for the measurement of inflammatory biomarkers (CRP, Il-6, MPO, TNF-alpha, MCP-1, Il-8, Il-10, and Il-18), prior to and following exposure to a standardized stress protocol. In univariate analyses, hostility was associated with significantly higher TNF-alpha, but lower Il-8 and Il-18 values post-stress, though only Il-8 remained significant after controlling for baseline differences. In multivariate analyses, a significant Age by Hostility interaction emerged for Il-6, while sex moderated the relation between hostility and Il-10 reactivity. Following stress, hostility was associated with greater pro-inflammatory Il-6 activity among younger individuals and to decreased anti-inflammatory Il-10 activity in women. Future research is needed to replicate these findings and to evaluate their implication for disease. PMID- 27270460 TI - Chronomodulated oxaliplatin plus Capecitabine (XELOX) as a first line chemotherapy in metastatic colorectal cancer: A Phase II Brunch regimen study. AB - PURPOSE: The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first line XELOX chemotherapy in patients with metastatic colorectal cancer. METHODS: A total of 30 treatment-naive colorectal cancer patients with metastatic disease were included. Oxaliplatin 130 mg/m(2) on day 1 plus chronomodulated oral capecitabine 2000 mg/m(2) per day were administered (50 % dose at 8:00 a.m. and 50 % dose at 12:00 noon on days 1-14, every 21 days). All adverse events, treatment responses and survival were evaluated. In addition, pharmacokinetic profile of capecitabine was examined in a subset of 5 patients. RESULTS: Median age was 57.1 years (range 32-77 years). Median follow-up was 19 months (range 3 36 months). Three patients (10 %) had complete response, 13 patients (43.3 %) had partial response and 4 patients (13.3 %) had stabile disease. Ten patients had progressive disease at their first evaluation (33.3 %). The median progression free survival (PFS) was 10 months (range 2-36 months). There were no grade 4 toxicities. One patient (3.3 %) had grade 3 neutropenia. Hand-foot syndrome developed in three patients (10 %): 6.6 %, grade 1 and 3.3 %, grade 2. CONCLUSIONS: Chronomodulated XELOX seems to represent a promising therapeutic option in the first-line treatment of metastatic colorectal carcinoma due to good tumor control and favorable toxicity profile. Phase III randomized trials are required to assess the actual clinical efficacy and side effect profile of this regimen. PMID- 27270462 TI - Advanced uracil DNA glycosylase-supplemented real-time reverse transcription loop mediated isothermal amplification (UDG-rRT-LAMP) method for universal and specific detection of Tembusu virus. AB - Tembusu virus (TMUV) is a mosquito-borne flavivirus which threatens both poultry production and public health. In this study we developed a complete open reading frame alignment-based rRT-LAMP method for the universal detection of TUMV. To prevent false-positive results, the reaction was supplemented with uracil DNA glycosylase (UDG) to eliminate carryover contamination. The detection limit of the newly developed UDG-rRT-LAMP for TMUV was as low as 100 copies/reaction of viral RNA and 1 * 10(0.89) - 1 * 10(1.55) tissue culture infectious dose/100 MUL of viruses. There were no cross-reactions with other viruses, and the reproducibility of the assay was confirmed by intra- and inter-assay tests with variability ranging from 0.22-3.33%. The new UDG-rRT-LAMP method for TMUV produced the same results as viral isolation combined with RT-PCR as the "gold standard" in 96.88% of cases for 81 clinical samples from subjects with suspected TMUV infection. The addition of UDG can eliminate as much as 1 * 10(-16) g/reaction of contaminants, which can significantly reduce the likelihood of false-positive results during the rRT-LAMP reaction. Our result indicated that our UDG-rRT-LAMP is a rapid, sensitive, specific, and reliable method that can effectively prevent carryover contamination in the detection of TMUV. PMID- 27270463 TI - Genome mining of lipolytic exoenzymes from Bacillus safensis S9 and Pseudomonas alcaliphila ED1 isolated from a dairy wastewater lagoon. AB - Dairy production plants produce highly polluted wastewaters rich in organic molecules such as lactose, proteins and fats. Fats generally lead to low overall performance of the treatment system. In this study, a wastewater dairy lagoon was used as microbial source and different screening strategies were conducted to select 58 lipolytic microorganisms. Exoenzymes and RAPD analyses revealed genetic and phenotypic diversity among isolates. Bacillus safensis, Pseudomonas alcaliphila and the potential pathogens, B. cereus, Aeromonas and Acinetobacter were identified by 16S-rRNA, gyrA, oprI and/or oprL sequence analyses. Five out of 10 selected isolates produced lipolytic enzymes and grew in dairy wastewater. Based on these abilities and their safety, B. safensis S9 and P. alcaliphila ED1 were selected and their genome sequences determined. The genome of strain S9 and ED1 consisted of 3,794,315 and 5,239,535 bp and encoded for 3990 and 4844 genes, respectively. Putative extracellular enzymes with lipolytic (12 and 16), proteolytic (20) or hydrolytic (10 and 15) activity were identified for S9 and ED1 strains, respectively. These bacteria also encoded other technological relevant proteins such as amylases, proteases, glucanases, xylanases and pectate lyases. PMID- 27270464 TI - Loop-mediated isothermal amplification assay targeting the mpb70 gene for rapid differential detection of Mycobacterium bovis. AB - Loop-mediated isothermal amplification (LAMP) is a highly sensitive, rapid, cost effective nucleic acid amplification method. Tuberculosis (TB) is widely popular in the world and it is difficult to cure. The fundamental treatment is to clear the types of TB pathogens such as Mycobacterium bovis (M. bovis), Mycobacterium tuberculosis (M. tuberculosis). In order to detect and diagnose TB early, we constructed the differential diagnostic method of TB. In this study, we used LAMP for detection of M. bovis, based on amplification of the mpb70 gene which is a unique gene in M. bovis strain. The LAMP assay was able to detect only seven copies of the gene per reaction, whereas for the conventional PCR, it was 70 copies. The LAMP was evaluated for its specificity using six strains of five Mycobacterium species and 18 related non-Mycobacterium microorganism strains as controls. The target three Mycobacterium strains were all amplified, and no cross reaction was found with 18 non-Mycobacterium microorganism strains. TB was detected by two methods, LAMP and conventional PCR (based on mpb70 gene); the positive rates of the two methods were 9.55 and 7.01 %, respectively. Our results indicate that the LAMP method should be a potential tool with high convenience, rapidity, sensitivity and specificity for the diagnosis of TB caused by M. bovis. Most importance is that the use of LAMP as diagnostic method in association with diagnostic tests based on mpb70 gene would allow the differentiation between M. bovis and other Mycobacterium in humans or animals. The LAMP method is actually in order to detect human TB, and it can be used for differential diagnosis in this paper. PMID- 27270465 TI - Twisting in the wind: intracorporeal ileocolic anastomosis. PMID- 27270466 TI - Impact of the first 5 years of a national abdominal aortic aneurysm screening programme. AB - BACKGROUND: The Abdominal Aortic Aneurysm (AAA) Screening Programme was introduced by the National Health Service (NHS) in England to reduce the rate of death from ruptured AAA in men. The programme commenced in 2009 and was implemented completely across the country in April 2013. The aim was to review the first 5 years of the programme, looking specifically at compliance and early outcome. METHODS: Men aged 65 years were invited for a single abdominal ultrasound scan. Data were entered into a bespoke database (AAA SMaRT). This was a planned analysis after the first 5 years of the programme. RESULTS: The summation analysis involved the first 700 000 men screened, and the first 1000 men with a large AAA referred for possible treatment. The prevalence of AAA (aortic diameter larger than 2.9 cm) in 65-year-old men was 1.34 per cent. Mean uptake was 78.1 per cent, but varied from 61.7 to 85.8 per cent across the country. Based on the Index of Multiple Deprivation, uptake was 65.1 per cent in the most deprived versus 84.1 per cent in the least deprived areas. Of the first 1000 men referred for possible treatment of a large AAA (greater than 5.4 cm), the false-positive rate was 3.2 per cent. Some 870 men underwent a planned AAA intervention (non-intervention rate 9.2 per cent), with seven deaths (perioperative mortality rate 0.8 per cent). CONCLUSION: The processes in the NHS AAA Screening Programme are effective in detecting and treating men with AAA. PMID- 27270467 TI - Early Childhood Developmental Status in Low- and Middle-Income Countries: National, Regional, and Global Prevalence Estimates Using Predictive Modeling. AB - BACKGROUND: The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs) are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development. METHODS AND FINDINGS: The present paper uses Early Childhood Development Index (ECDI) data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS) and Demographic and Health Surveys (DHS) programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI) and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million) in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y), followed by South Asia (27.7 million; 37.7%) and the East Asia and Pacific region (15.1 million; 25.9%). Positive associations were found between low development scores and stunting, poverty, male sex, rural residence, and lack of cognitive stimulation. Additional research using more detailed developmental assessments across a larger number of LMICs is needed to address the limitations of the present study. CONCLUSIONS: The number of children globally failing to reach their developmental potential remains large. Additional research is needed to identify the specific causes of poor developmental outcomes in diverse settings, as well as potential context-specific interventions that might promote children's early cognitive and socioemotional well-being. PMID- 27270468 TI - Cytokine and Chemokine Expression in CSF May Differentiate Viral and Autoimmune NMDAR Encephalitis in Children. AB - Childhood encephalitis is a potentially devastating condition with significant morbidity and mortality. Researchers currently lack biomarkers for differentiating infectious encephalitis from those with autoimmune causes which may delay adequate treatment. The authors studied the possibility of using cerebrospinal fluid cytokine and chemokine levels for this purpose. Children admitted to hospital care fulfilling criteria for encephalitis were prospectively included. Children who underwent lumbar puncture but were not classified as central nervous system infections served as controls. Cytokine and chemokine levels in the cerebrospinal fluid obtained upon initial presentation were analyzed using Luminex technology. In children with infectious encephalitis (n = 13), the cerebrospinal fluid displayed markedly elevated mean levels of IL6, IL7, and IL13 as compared to N-methyl-D-aspartate receptor (NMDAR) encephalitis (n = 4) and controls (n = 13). The expression of IL6 appeared to precede that of IL13. Analysis of selected cerebrospinal fluid cytokines may thus allow differential diagnosis of infectious and NMDAR encephalitis already at the initial lumbar puncture and enable immediate therapy. PMID- 27270469 TI - Peripheral Vascular Restenosis: A Retrospective Study on the Use of Drug-Eluting Balloons in Native Arteries, Vein Grafts and Dialysis Accesses. AB - BACKGROUND AND AIMS: The objective of this study is to analyze outcomes of the first experiences with drug-eluting balloons in native arteries, vein grafts, and vascular accesses. The study is also a pilot for our future prospective, randomized, and controlled studies regarding the use of drug-eluting balloons in the treatment of the stenosis in bypass vein graft and dialysis access. MATERIALS AND METHODS: A total of 93 consecutive patients were retrospectively analyzed and in the end 81 were included in the study. Inclusion criteria included at least one previous percutaneous angioplasty to the same lesion. Patients were divided into three groups according to the anatomical site of the lesion: native lower limb artery, vein bypass graft, or vascular access. Time from the previous percutaneous angioplasty to the drug-eluting balloon was compared to the time from the drug-eluting balloon to endpoint in the same patient. Endpoints included any new revascularization of the target lesion, major amputation, or new vascular access. RESULTS: The median time from the drug-eluting balloon to endpoint was significantly longer than the median time from the preceding percutaneous angioplasty to drug-eluting balloon in all three groups. This difference was clearest in native arteries and vein grafts, whereas the difference was smaller from the beginning and disappeared over time in the vascular access group. No significant differences were seen between the groups with regard to smoking, antiplatelet regime, diabetes, Rutherford classification, or sex. CONCLUSION: Although the setup of this study has several limitations, the results suggest that there could be benefit from drug-eluting balloons in peripheral lesions. Very little data have been published on the use of drug-eluting balloons in vein grafts and vascular accesses, and randomized and controlled prospective studies are needed to further investigate this field. PMID- 27270470 TI - Effects of high-speed power training on muscle strength and power in patients with multiple sclerosis. AB - This study examined the effects of a high-speed power training program in peak muscle power and maximal voluntary isometric contraction (MVIC) of knee extensors in patients with relapsing-remitting multiple sclerosis (MS). Forty patients, 20 women (age 42.8 +/- 10.3 yr) and 20 men (age 44.0 +/- 8.7 yr) diagnosed with relapsing-remitting MS were randomly assigned, with respect to sex, to either an exercise group or a control group. Participants from the exercise group performed 12 wk of supervised muscle power training of knee extensors. All subjects were tested for MVIC and peak muscle power at baseline and after the training intervention. A strain gauge was used to measure the MVIC, and peak muscle power was assessed with a linear encoder at five relative loads. The training-related effects were assessed using a t-test. The results showed no significant changes in the control group from baseline to postintervention evaluation. In contrast, the exercise group significantly increased MVIC (10.8%; p < 0.05) and muscle power at 40, 50, 60, 70, and 80% of the MVIC by 21.8, 14.5, 17.3, 19.4, and 22.3%, respectively (p < 0.01), after the training. These findings suggest that 12 wk of high-speed power training improve both MVIC and muscle power at five different loads in patients with relapsing-remitting MS. PMID- 27270471 TI - The Brand's PREACH Model: Predicting Readiness to Engage African American Churches in Health. AB - Despite many attempts to reduce health disparities, health professionals face obstacles in improving poor health outcomes within the African American (AA) community. To promote change for improved health measures, it is important to implement culturally tailored programming through a trusted institution, such as the AA church. While churches have the potential to play an important role in positively impacting health among AAs, it is unclear what attributes are necessary to predict success or failure for health promotion within these institutions. The purpose of this study was to create a model, the Brand's PREACH ( Predicting Readiness to Engage African American Churches in Health) Model, to predict the readiness of AA churches to engage in health promotion programming. Thirty-six semistructured key informant interviews were conducted with 12 pastors, 12 health leaders, and 12 congregants to gain information on the relationship between church infrastructure (physical structure, personnel, funding, and social/cultural support), readiness, and health promotion programming. The findings revealed that church infrastructure has an association with and will predict the readiness of a church to engage in health promotion programming. The ability to identify readiness early on will be useful for developing, implementing, and evaluating faith-based interventions, in partnership with churches, which is a key factor for sustainable and effective programs. PMID- 27270472 TI - Systemic lupus erythematosus associated with myasthenia gravis, pemphigus foliaceus and chronic thyroiditis after thymectomy. AB - A 65-year-old woman had undergone a thymectomy for thymoma and 1 year after surgery she developed scattered erosive erythema with scaling and crusting. Examination findings exhibited the elevation of anti-dsDNA antibody, anti desmoglein 1 antibody, anti-acetylcholine receptor antibody and anti thyroglobulin antibody. A skin biopsy showed intraepidermal blisters containing neutrophils and acantholytic keratinocytes and direct immunofluorescence revealed the deposition of immunoglobulin G in the epidermis and on the basement membrane. These findings indicated the presence of systemic lupus erythematosus (SLE), myasthenia gravis, pemphigus foliaceus and chronic thyroiditis. Only 1% of SLE patients have three other autoimmune diseases according to previous publications. Our case is rare because she suffered four autoimmune diseases after the thymectomy. PMID- 27270473 TI - Thyroid Function and the Risk of Nonalcoholic Fatty Liver Disease: The Rotterdam Study. AB - CONTEXT: Although thyroid function is associated with several risk factors of nonalcoholic fatty liver disease (NAFLD), its role in NAFLD development remains unclear. OBJECTIVE: We aimed to prospectively investigate the association between variations in thyroid function and NAFLD. DESIGN AND SETTING: The Rotterdam Study, a large population-based, prospective cohort study. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants with thyroid function measurements at baseline and NAFLD data (ie, at baseline fatty liver index/at follow-up ultrasound) were eligible. Transient elastography was performed to assess the presence of fibrosis in patients with NAFLD, using the liver stiffness measurements more than or equal to 8 kPa as cutoff for clinically relevant fibrosis. The association between thyroid parameters and incident NAFLD was explored by using logistic regression models. RESULTS: A total of 9419 participants (mean age, 64.75 y) were included. The median follow-up time was 10.04 years (interquartile range, 5.70-10.88 y). After adjusting for age, sex, cohort, follow-up time, use of hypolipidemic drugs, and cardiovascular risk factors, higher free T4 levels were associated with a decreased risk of NAFLD (odds ratio, 0.42; 95% confidence interval [CI], 0.28 0.63). In line, higher TSH levels were associated with an increased risk of having clinically relevant fibrosis in NAFLD (odds ratio, 1.49; CI, 1.04-2.15). Compared with euthyroidism, hypothyroidism was associated with a 1.24-fold higher NAFLD risk (CI, 1.01-1.53). Moreover, NAFLD risk decreased gradually from hypothyroidism to hyperthyroidism (P for trend = .003). CONCLUSION: Lower thyroid function is associated with an increased NAFLD risk. These findings may lead to new avenues regarding NAFLD prevention and treatment. PMID- 27270474 TI - Lipoprotein (a), the Metabolic Syndrome and Vascular Risk in Angiographied Coronary Patients. AB - BACKGROUND: Lipoprotein (a) [Lp(a)] especially in young individuals, is an important cardiovascular risk factor. However, data on the vascular risk conferred by Lp(a) in patients with the metabolic syndrome (MetS) are not available. METHODS: Lp(a) was measured in a cohort of 593 consecutive patients undergoing coronary angiography for the evaluation of stable coronary artery disease. MetS was diagnosed according to International Diabetes Federation criteria. Vascular events were recorded over 10 years. RESULTS: Median Lp(a) was significantly lower in patients with the MetS (n = 307) than in subjects who did not have the MetS (12 [interquartile range, 0-35] mg/dl vs 17 [0-57] mg/dl; P = .004). Prospectively, 34% of our patients suffered vascular events. Lp(a) proved to be a strong and independent predictor of vascular events in subjects without the MetS (standardized adjusted hazard ratio [HR], 1.20 [1.05-1.38]; P = .006) but not in patients who had the MetS (HR, 0.96 [0.77-1.20]; P = .713). An interaction term MetS * Lp(a) was significant (P = .029), indicating that Lp(a) was a significantly stronger predictor of vascular events in subjects without the MetS than in patients with the MetS. CONCLUSIONS: Lp(a) in patients with the MetS is low and is not associated with the incidence of vascular events. The power of Lp(a) as a predictor of cardiovascular events is significantly modulated by the presence of the MetS. PMID- 27270475 TI - Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes. AB - CONTEXT: Bile acids regulate lipid and carbohydrate metabolism by interaction with membrane or intracellular proteins including the nuclear farnesoid X receptor (FXR). Postprandial activation of ileal FXR leads to secretion of fibroblast growth factor 19 (FGF-19), a gut hormone that may be implicated in postprandial glucose metabolism. OBJECTIVE: To describe postprandial plasma concentrations of 12 individual bile acids and FGF-19 in patients with type 2 diabetes (T2D) and healthy controls. DESIGN AND SETTING: Descriptive study, performed at the Center for Diabetes Research, Gentofte Hospital, Hellerup, Denmark. PARTICIPANTS: Fifteen patients with T2D and 15 healthy matched controls with normal glucose tolerance. INTERVENTIONS: A 75-g oral glucose tolerance test and three isocaloric and isovolemic liquid meals with low, medium, and high fat content, respectively. MAIN OUTCOME MEASURES: Bile acid and FGF-19 concentrations. RESULTS: Postprandial total bile acid concentrations increased with increasing meal fat content (P < .05), peaked after 1-2 hours, and were higher in T2D patients vs controls (oral glucose tolerance test, low and medium fat meals, P < .05; high fat meal, P = .30). Differences reflected mainly unconjugated and glycine-conjugated forms of deoxycholic acid (DCA) and to a lesser extent cholic acid (CA) and ursodeoxycholic acid (UDCA), whereas chenodeoxycholic acid (CDCA) concentrations were comparable in the two groups. FGF-19 concentrations tended to be lower in T2D patients vs controls, but differences were not statistically significant due to considerable variation. CONCLUSION: Postprandial plasma patterns of bile acids with FXR agonistic properties (CDCA, DCA, and CA) and FXR antagonistic properties (UDCA) in T2D patients support the notion of a "T2D-bile acid-FGF-19" phenotype with possible pathophysiological implications. PMID- 27270476 TI - Genetic Variations in FSH Action Affect Sex Hormone Levels and Breast Tissue Size in Infant Girls: A Pilot Study. AB - CONTEXT: Single nucleotide polymorphisms altering FSH action (FSHB -211G>T, FSHR 29G>A, and FSHR 2039A>G) are associated with peripubertal and adult levels of reproductive hormones and age at pubertal onset in girls. OBJECTIVE: To investigate whether genetic polymorphisms altering FSH action affect serum levels of female reproductive hormones and breast development as early as during minipuberty. DESIGN: Longitudinal study. SETTING: Population-based cohort study. PARTICIPANTS: A total of 402 healthy girls at 3 months of age. MAIN OUTCOME MEASURES: Analyses of single nucleotide polymorphisms by PCR using Kompetitive Allele Specific PCR genotyping assays; identification of glandular breast tissue by palpation and measurement of the diameter. Serum levels of anti-Mullerian hormone, FSH, LH, estradiol, inhibin B, and sex hormone-binding globulin were assessed by immunoassays. RESULTS: FSHR -29G>A was associated with both FSH and anti-Mullerian hormone levels with an A allele effect size of -0.8 IU/L (P = .005) and 1.4 nmol/L (P = .003), respectively. FSHR 2039A>G correlated with breast tissue size with a negative additive effect of minor alleles (P = .021), whereas the effect on estradiol levels was only present in homozygotes. FSHB 211T carriers had smaller breast tissue size than girls who without a minor allele; GT+TT 10.5 (confidence interval 9.4-11.5) mm vs GG 12.1 (confidence interval 11.4-12.8) mm, P = .014. CONCLUSIONS: Our study indicates that 3 genetic polymorphisms altering FSH action, especially FSHR -29G>A and FSHR 2039A>G, affect female hormone profile and glandular breast tissue development already during minipuberty. Thus, genetic variations of FSH signaling appear to determine the individual set point of the hypothalamic-pituitary-gonadal axis already early in life. PMID- 27270477 TI - PRKACA Somatic Mutations Are Rare Findings in Aldosterone-Producing Adenomas. AB - CONTEXT: Somatic mutations have been found causative for endocrine autonomy in aldosterone-producing adenomas (APAs). Whereas mutations of PRKACA (catalytic subunit of protein kinase A) have been identified in cortisol-producing adenomas, the presence of PRKACA variants in APAs is unknown, especially in those that display cosecretion of cortisol. OBJECTIVE: The objective of the study was to investigate PRKACA somatic variants identified in APA cases. DESIGN: Identification of PRKACA somatic variants in APAs by whole-exome sequencing followed by in vitro analysis of the enzymatic activity of PRKACA variants and functional characterization by double immunofluorescence of CYP11B2 and CYP11B1 expression in the corresponding tumor tissues. SETTING AND PATIENTS: APA tissues were collected from 122 patients who underwent unilateral adrenalectomy for primary aldosteronism between 2005 and 2015 at a single institution. RESULTS: PRKACA somatic mutations were identified in two APA cases (1.6%). One APA carried a newly identified p.His88Asp variant, whereas in a second case, a p.Leu206Arg mutation was found, previously described only in cortisol-producing adenomas with overt Cushing's syndrome. Functional analysis showed that the p.His88Asp variant was not associated with gain of function. Although CYP11B2 was strongly expressed in the p.His88Asp-mutated APA, the p.Leu206Arg carrying APA predominantly expressed CYP11B1. Accordingly, biochemical Cushing's syndrome was present only in the patient with the p.Leu206Arg mutation. After adrenalectomy, both patients improved with a reduced number of antihypertensive medications and normalized serum potassium levels. CONCLUSIONS: We describe for the first time PRKACA mutations as rare findings associated with unilateral primary aldosteronism. As cortisol cosecretion occurs in a subgroup of APAs, other molecular mechanisms are likely to exist. PMID- 27270478 TI - Efficacy and Safety of Panobinostat in Relapsed or/and Refractory Multiple Myeloma: Meta Analyses of Clinical Trials and Systematic Review. AB - During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer relapsing. Thus, novel therapeutic agents are needed. We aimed to assess the efficacy and safety of a novel agent panobinostat for patients with relapsed or/and refractory MM. A systematic literature review identified studies for clinical trials about panobinostat in patients with relapsed or/and refractory MM. We searched studies published between January 2000 and December 2015 in Pubmed, Ovid, EBSCO and the Cochrane library. Random-effect pooled estimates were calculated for overall response rate and rates of common adverse effects. The results showed 11 clinical trials including 700 patients with relapsed or/and refractory MM treated with panobinostat were identified. The ORR varied between 0.08 and 0.67. Pooled analyses showed the results that the ORR was 0.45 (95% CI: 0.31-0.59, I(2) = 90.5%, P = 0.000) for panobinostat combined with any other kind of drugs. The most common Grade3/4 adverse effects were thrombocytopenia, neutropenia, lymphopenia, anemia, diarrhea, fatigue, nausea and so on. In conclusion, based on our analyses, the regimen of panobinostat combining with other agents seems to be well tolerated and efficacious in patients with relapsed or/and refractory MM. PMID- 27270479 TI - Management of postoperative bleeding after laparoscopic left colectomy. AB - BACKGROUND: Lower gastrointestinal bleeding after left colectomy is an uncommon complication that can lead to critical situation. Diagnostic and therapeutic manoeuvres should be performed in emergency with step-by-step strategy in order to avoid reoperation. This study aims to identify bleeding risks factors and describe a management strategy. METHODS: This is a retrospective study of patients who underwent left colectomy with primary anastomosis, from May 2004 to December 2013. We studied their demographic characteristics, surgical procedures and postoperative courses, more specifically hemorrhagic complications, management of bleeding and outcomes. RESULTS: Hemorrhagic anastomotic complication occurred in 47 of the 729 (6.4 %) patients after left colectomy. Neither anticoagulant nor antiaggregant treatment was associated with postoperative bleeding. Among the 47 patients with bleeding, endoscopy was performed in 37 (78.7 %). At the time of endoscopy, the bleeding was spontaneously stopped in nine (24.3 %). Therapeutic strategy used clips in 10 (27.0 %) cases, mucosal sclerosis in 11 (29.7 %) and both in 7 (18.9 %) cases. Four (8.5 %) patients required blood transfusion for treatment of this gastrointestinal bleeding. Five (10.6 %) patients with bleeding were reoperated in this group because early endoscopy showed associated anastomotic leakage. Based on a multivariate analysis, stapled anastomosis and diverticular disease were independent factors associated with anastomotic bleeding. CONCLUSIONS: Postoperative anastomotic bleeding is not so uncommon after left colectomy. This complication should be particularly dreaded in patients who underwent stapled colorectal anastomosis for diverticular disease. With the use of clip or mucosal sclerosis, early endoscopy is a safe and efficient treatment. PMID- 27270480 TI - Erectile and urinary function in men with rectal cancer treated by neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy alone: a randomized trial report. AB - OBJECTIVE: The aim was to evaluate erectile and urinary function of male patients with rectal cancer treated by neoadjuvant (NA) chemoradiotherapy (CRT) or NA chemotherapy only. METHODS: In this prospective randomized trial (ClinicalTrials.gov NCT01211210; "FOWARC"), we included 102 men who received NA therapy for stage II-III rectal cancer between January 2011 and June 2013. Before surgery, patients received either NA mFOLFOX6 chemotherapy with radiation (RCS group, n = 54) or NA mFOLFOX6 chemotherapy alone (CS group, n = 48). Erectile and urinary dysfunctions were assessed with the five-item International Index of Erectile Function (IIEF-5) scale and the International Prostatic Symptom Score (IPSS), respectively. Questionnaires were completed at baseline and at 3, 6, and 12 months (t0-t3, respectively) after surgery. RESULTS: At t3, mean IIEF-5 score was significant higher in the CS group (15.3 +/- 5.5) than in the RCS group (12.6 +/- 5.7; P < 0.05). And score difference was statistically higher in RCS group compared with CS group at t2 and t3, especially t3 (9.3 +/- 5.5 vs. 6.1 +/- 5.1, P < 0.01). Univariate analysis of the RCS group's IIEF-5 scores associated age, stoma, location, and tumor size to erectile dysfunction. However, mean IPSS scores did not differ between the two groups at any point. CONCLUSIONS: Compared with the CS group, erectile and urinary functions were significantly affected by NA CRT. Age, stoma, tumor location, and tumor size were also correlated with erectile dysfunction in the RCS group. PMID- 27270481 TI - Monitoring urban growth by using segmentation-classification of multispectral Landsat images in Izmit, Turkey. AB - Assessing the spatial land use and land cover (LULC) information is essential for decision making and management of landscapes. In fact, LULC information has been changed dramatically in fast-growing cities. This results in wrong land use problems due to unplanned and uncontrolled urbanization. The planning and evaluating of limited natural resources under the pressure of a growing population can be possible when a precise land use management plan is established. Therefore, it is imperative to monitor continuous LULC changes for future planning. Remote sensing (RS) technique is used for determining changes in LULC in urban areas. In this study, we have focused on Izmit, which is one of a growing number of metropolitan cities where the impact of the spatial growing period on LULC has been assessed over the past 30 years by using RS data. We have utilized the segmentation process and supervised classification of Landsat satellite images for four different dates (1985, 1995, 2005, and 2015). The outcome of this research can be summarized by significant changes in the shares of urban areas and farmland LULC classes. The overall observed increase in urban area class is up to 2177 ha between 1985 and 2015 period and this dramatic change has resulted in the decline of 1211 ha of farmland. Another conclusion is that the new residential areas have been created to the north, south and east of Izmit during this period. PMID- 27270482 TI - Effects of dredging at Aratu port in All Saints Bay, Brazil: monitoring the metal content in water and sediments. AB - This work reports the chemical monitoring of saline water and sediments at Aratu port, All Saints Bay, Brazil, when subjected to a deep dragging process (DDP) over a 2-year period (2010-2012). The aim of this work was to detect which metals had possible deleterious effects on the biota. It analyzed percentage of silt + clay and TOC and metal concentrations (As, Cd, Cu, Cr, Ni, Pb, and Zn) before, during, and after the DDP. The determination of metal concentration in sediments used the following techniques: atomic absorption spectrometer with flame, also with hydrate generation, and cold vapor spectrophotometry. The DDP disturbed the concentrations of metals in sediments and water, but 15 months after the DDP, only Cu and Zn were detectable on the bottom saline water, and 20 months after the DDP, only Zn was detectable in water. This fact indicates that these metals were longer available for absorption by the marine biota with probable deleterious effect. Indeed, studies by others during the DDP in Aratu port, indicated the decrease from 50 to 40 of the number of microalgae species identified. On the other hand, in the sediments, 20 months after the DDP, the concentrations of As, Cr, Cu, Pb, and Hg, returned to the original values, but Ni and Zn did not return to their original values. Comparison with studies by others indicated that the sediments from dredging were inappropriate for disposal at sea. This work indicated that the metals Cu, Ni, and Zn are the most deleterious elements to the marine environment. PMID- 27270483 TI - Sources and seasonal variation of coliform bacteria abundance in groundwater around the slopes of Mount Meru, Arusha, Tanzania. AB - The quality of the groundwater along the slopes of Mount Meru, Tanzania, is poorly understood. Water access and sanitation practices may pose health risks to communities. This study was undertaken to assess the sources, abundance and seasonal variation of coliform bacteria in groundwater and factors contributing to such variations along slopes of Mount Meru, Tanzania. Water samples collected from 67 randomly selected water sources (springs, shallow wells which ranged from 4 to 35 m deep and Boreholes above 40 m deep) during dry and wet seasons were analysed for total coliform (TC), faecal coliform (FC), Escherichia coli (E. coli) and faecal streptococci (FS), using the membrane filtration method. The fraction of springs and shallow wells contaminated was generally higher compared to the fraction of boreholes. The highest TC, FC, E. coli and FS counts were significantly higher (p < 0.05) during the wet than the dry season owing to rising of water table and leaching during rainy season. Water sources that were located within 10 m of pit latrines had the highest coliform counts relative to those located beyond 10 m. Similarly, the highest coliform counts were observed in all shallow wells that (i) had low well head above the ground, (ii) were not covered, (iii) had casing materials which were not concrete and (iv) utilised traditional pumping (bucket/pulley) systems. This was due to contaminated storm water access, inoculation of microbes by exposed buckets and inefficiency of the casing material. Furthermore, the counts decreased with depths of boreholes and shallow wells during the two seasons probably due to retention and die-off. It is recommended that groundwater in this area be treated against coliform contamination prior to utilisation as portable water. PMID- 27270484 TI - Detecting the environmental impact of off-road vehicles on Rawdat Al Shams in central Saudi Arabia by remote sensing. AB - Off-road vehicles can have a devastating impact on vegetation and soil. Here, we sought to quantify, through a combination of field vegetation, bulk soil, and image analyses, the impact of off-road vehicles on the vegetation and soils of Rawdat Al Shams, which is located in central Saudi Arabia. Soil compaction density was measured in the field, and 27 soil samples were collected for bulk density analysis in the lab to quantify the impacts of off-road vehicles. High spatial resolution images, such as those obtained by the satellites GeoEye-1 and IKONOS-2, were used for surveying the damage to vegetation cover and soil compaction caused by these vehicles. Vegetation cover was mapped using the Normalized Difference Vegetation Index (NDVI) technique based on high-resolution images taken at different times of the year. Vehicle trails were derived from satellite data via visual analysis. All damaged areas were determined from high resolution image data. In this study, we conducted quantitative analyses of vegetation cover change, the impacts of vehicle trails (hereafter "trail impacts"), and a bulk soil analysis. Image data showed that both vegetation cover and trail impacts increased from 2008 to 2015, with the average percentage of trail impacts nearly equal to that of the percentage of vegetation cover during this period. Forty-six species of plants were found to be present in the study area, consisting of all types of life forms, yet trees were represented by a single species, Acacia gerrardii. Herbs composed the largest share of plant life, with 29 species, followed by perennial herbs (12 species), grasses (5 species), and shrubs (3 species). Analysis of soil bulk density for Rawdat Al Shams showed that off-road driving greatly impacts soil density. Twenty-two plant species were observed on the trails, the majority of which were ephemerals. Notoceras bicorne was the most common, with a frequency rate of 93.33 %, an abundance value of 78.47 %, and a density of 0.1 in transect 1, followed by Plantago ovata. PMID- 27270485 TI - Spatial assessment and source identification of trace metal pollution in stream sediments of Oued El Maadene basin, northern Tunisia. AB - An extensive spatial survey was conducted on trace metal content in stream sediments from Oued El Maadene basin, northern Tunisia. Our objectives were to evaluate the level of trace metal pollution and associated ecological risk and identify the major sources of metal pollution. A total of 116 stream sediment samples were collected and analysed for total As, Cd, Cr, Cu, Ni, Pb, V, Zn, and Zr concentrations. The results showed that concentrations of Cr, Ni, V, and Zr were close to natural levels. In contrast, As, Cd, Cu, Pb, and Zn had elevated concentrations and enrichment factors compared to other contaminated regions in northern Tunisia. Ecological risk to aquatic ecosystems was highlighted in most areas. Principal component analysis showed that Cr, Ni, V, and Zr mainly derived from local soil and bedrock weathering, whilst As, Cd, Pb, and Zn originated from mining wastes. Trace metals could be dispersed downstream of tailings, possibly due to surface runoff during the short rainy season. Surprisingly, Cu, and to a lesser extent As, originated from agricultural activities, related to application of Cu-based fungicides in former vineyards and orchards. This study showed that, despite the complete cessation of mining activities several decades ago, metal pollution still impacts the local environment. This large pollution, however, did not mask other additional sources, such as local agricultural applications of fungicides. PMID- 27270486 TI - Nitrogen Chemistry and Coke Transformation of FCC Coked Catalyst during the Regeneration Process. AB - Regeneration of the coked catalyst is an important process of fluid catalytic cracking (FCC) in petroleum refining, however, this process will emit environmentally harmful gases such as nitrogen and carbon oxides. Transformation of N and C containing compounds in industrial FCC coke under thermal decomposition was investigated via TPD and TPO to examine the evolved gaseous species and TGA, NMR and XPS to analyse the residual coke fraction. Two distinct regions of gas evolution are observed during TPD for the first time, and they arise from decomposition of aliphatic carbons and aromatic carbons. Three types of N species, pyrrolic N, pyridinic N and quaternary N are identified in the FCC coke, the former one is unstable and tends to be decomposed into pyridinic and quaternary N. Mechanisms of NO, CO and CO2 evolution during TPD are proposed and lattice oxygen is suggested to be an important oxygen resource. Regeneration process indicates that coke-C tends to preferentially oxidise compared with coke N. Hence, new technology for promoting nitrogen-containing compounds conversion will benefit the in-situ reduction of NO by CO during FCC regeneration. PMID- 27270487 TI - Sex differences in response to miRNA-34a therapy in mouse models of cardiac disease: identification of sex-, disease- and treatment-regulated miRNAs. AB - KEY POINTS: MicroRNA (miRNA)-based therapies are in development for numerous diseases, including heart disease. Currently, very limited basic information is available on the regulation of specific miRNAs in male and female hearts in settings of disease. The identification of sex-specific miRNA signatures has implications for translation into the clinic and suggests the need for customised therapy. In the present study, we found that a miRNA-based treatment inhibiting miRNA-34a (miR-34a) was more effective in females in a setting of moderate dilated cardiomyopathy than in males. Furthermore, the treatment showed little benefit for either sex in a setting of more severe dilated cardiomyopathy associated with atrial fibrillation. The results highlight the importance of understanding the effect of miRNA-based therapies in cardiac disease settings in males and females. ABSTRACT: MicroRNA (miRNA)-34a (miR-34a) is elevated in the diseased heart in mice and humans. Previous studies have shown that inhibiting miR-34a in male mice in settings of pathological cardiac hypertrophy or ischaemia protects the heart against progression to heart failure. Whether inhibition of miR-34a protects the female heart is unknown. Furthermore, the therapeutic potential of silencing miR-34a in settings of dilated cardiomyopathy (DCM) and atrial fibrillation (AF) has not been assessed previously. In the present study, we examined the effect of silencing miR-34a in males and females in (1) a model of moderate DCM and (2) a model of severe DCM with AF. The cardiac disease models were administered with a locked nucleic acid-modified oligonucleotide (LNA antimiR-34a) at 6-7 weeks of age when the models display cardiac dysfunction and conduction abnormalities. Cardiac function and morphology were measured 6 weeks after treatment. In the present study, we show that inhibition of miR-34a provides more protection in the DCM model in females than males. Disease prevention in LNA-antimiR-34a treated DCM female mice was characterized by attenuated heart enlargement and lung congestion, lower expression of cardiac stress genes (B-type natriuretic peptide, collagen gene expression), less cardiac fibrosis and better cardiac function. There was no evidence of significant protection in the severe DCM and AF model in either sex. Sex- and treatment dependent regulation of miRNAs was also identified in the diseased heart, and may explain the differential response of males and females. These studies highlight the importance of examining the impact of miRNA-based drugs in both sexes and under different disease conditions. PMID- 27270489 TI - The limits of public communication coordination in a nuclear emergency: lessons from media reporting on the Fukushima case. AB - Coordination of public communication has become a key issue in management of complex emergencies, and is a matter of debate between nuclear emergency management professionals. A particular problem is when inconsistent information is sent to the media and public by official sources from different levels, which has led to calls for a more coordinated approach. The IAEA created guidelines recommending a one-voice communication approach that provides clear, consistent and coordinated information by relevant stakeholders. The reviewed theory on the emergency communication coordination and the empirical results in this paper demonstrate some challenges regarding the feasibility of the above stated goal. This paper explores the communication process in the two-month period of the Fukushima nuclear emergency by using a quantitative comparative content and discourse analysis of 1340 printed media articles on the Fukushima nuclear disaster from two major newspapers in Spain ('El Pais' and 'El Mundo'), Italy ('Corriere della Sera' and 'La Repubblica'), Norway ('Aftenposten' and 'Dagsavisen'), Slovenia ('Delo' and 'Vecer'), Belgium ('Le Soir' and 'De Standaard') and Russia ('Komsomolskaya Pravda' and 'Izvestiya'). The results show that it will be difficult to achieve a truly coordinated approach and one-voice communication in severe nuclear and radiological emergency due to the communication difficulties created by the dispersion of information sources, a broad and dispersed focus of the reported information, partially subjective and conflicting media reporting. The paper suggests ways to improve public communication coordination in nuclear and radiological disasters. PMID- 27270490 TI - Anatomic variations of brachial and lumbosacral plexus models in different rat strains. AB - PURPOSE: Selection of an appropriate model for preclinical assessment of new methods of peripheral nerve injury management is crucial. This report presents anatomic variations within brachial and lumbosacral plexuses in three selected rat strains Sprague Dawley (Hsd:Sprague Dawley SD), Lewis (LEW/SsNHsd), and Athymic Nude (Hsd:RH-Foxn1rnu ) rats. METHODS: Based on their strain eighteen rats were divided into three groups. A total of 90 brachial plexus nerves (axillary, musculocutaneous, median, ulnar, and radial nerves) and 72 lumbosacral plexus nerves (sciatic, tibial, common peroneal, and sural nerves) were analyzed for the length, diameter and correlation with the body weight. A detailed anatomic course of each nerve within the brachial and lumbosacral plexuses was outlined. RESULTS: The sural nerve was the longest nerve in all studied rat strains, whereas the sciatic nerve had the largest diameter. Comparison of all the nerves' length demonstrated that the Lewis rat sciatic and sural nerves were significantly shorter (P < 0.05). No significant differences in nerve diameters were found among the analyzed rat strain groups. Significant correlation was revealed between the length of sciatic nerve and the rats' weight, which is irrelevant to the rats' genetic background. CONCLUSIONS: This study confirmed that nerves' length within rat's brachial and lumbosacral plexus depends on the inter-individual variations within the rat strains rather than on the differences in the peripheral nerve development, which is inherent to the specific rat strain. Correlation between the nerve length and body weight, suggests that bigger rats should be considered for studies requiring access to the long nerves. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:327-333, 2017. PMID- 27270491 TI - IRAK regulates macrophage foam cell formation by modulating genes involved in cholesterol uptake and efflux. AB - Interleukin-1 receptor-associated kinase-1 (IRAK1) is linked to the pathogenesis of atherosclerosis; however, its role in macrophage foam cell formation is not known. Therefore, the present study investigated the role of IRAK1 in lipid uptake, biosynthesis, and efflux in THP-1 derived macrophages and human monocyte derived macrophages (HMDMs). Ox-LDL (40 MUg/mL, 15 minutes-48 hours) treatment induced time-dependent increase in IRAK1, IRAK4, and Stat1 activation in THP-1 derived macrophages. IRAK1/4 inhibitor (INH) or IRAK1 siRNA significantly attenuated cholesterol accumulation, DiI-Ox-LDL binding, and uptake while cholesterol efflux to apoAI and HDL was enhanced in THP-1 derived macrophages and HMDMs. Ox-LDL treatment significantly increased the mRNA expression of CD36, LOX 1, SR-A, ABCA1, ABCG1, Caveolin-1, CYP27A1 while that of SR-BI was decreased. IRAK1/4 inhibition or IRAK1 knockdown, however, attenuated Ox-LDL-induced CD36 expression; augmented ABCA1 and ABCG1 expression while expression of others was unaffected in THP-1 derived macrophages and HMDMs. Moreover, IRAK1/4 inhibition had no significant effect on genes involved in lipid biosynthesis. In IRAK1/4 INH pre-treated THP-1 derived macrophages Ox-LDL-induced Stat1 phosphorylation and its binding to CD36 promoter was significantly attenuated while LXRalpha expression and its binding to the ABCA1/ABCG1 locus, NFATc2 activation and its binding to ABCA1 locus was enhanced. The present study thus demonstrates that IRAK regulates lipid accumulation by modulating CD36-mediated uptake and ABCA1-, ABCG1-dependent cholesterol efflux. Therefore, IRAK1 can be a potential target for preventing macrophage foam cell formation. PMID- 27270488 TI - SCN8A encephalopathy: Research progress and prospects. AB - On April 21, 2015, the first SCN8A Encephalopathy Research Group convened in Washington, DC, to assess current research into clinical and pathogenic features of the disorder and prepare an agenda for future research collaborations. The group comprised clinical and basic scientists and representatives of patient advocacy groups. SCN8A encephalopathy is a rare disorder caused by de novo missense mutations of the sodium channel gene SCN8A, which encodes the neuronal sodium channel Nav 1.6. Since the initial description in 2012, approximately 140 affected individuals have been reported in publications or by SCN8A family groups. As a result, an understanding of the severe impact of SCN8A mutations is beginning to emerge. Defining a genetic epilepsy syndrome goes beyond identification of molecular etiology. Topics discussed at this meeting included (1) comparison between mutations of SCN8A and the SCN1A mutations in Dravet syndrome, (2) biophysical properties of the Nav 1.6 channel, (3) electrophysiologic effects of patient mutations on channel properties, (4) cell and animal models of SCN8A encephalopathy, (5) drug screening strategies, (6) the phenotypic spectrum of SCN8A encephalopathy, and (7) efforts to develop a bioregistry. A panel discussion of gaps in bioregistry, biobanking, and clinical outcomes data was followed by a planning session for improved integration of clinical and basic science research. Although SCN8A encephalopathy was identified only recently, there has been rapid progress in functional analysis and phenotypic classification. The focus is now shifting from identification of the underlying molecular cause to the development of strategies for drug screening and prioritized patient care. PMID- 27270492 TI - Erratum to: Mutant SOD1 protein increases Nav1.3 channel excitability. PMID- 27270493 TI - Reply. PMID- 27270494 TI - The effectiveness of family-based treatment for full and partial adolescent anorexia nervosa in an independent private practice setting: Clinical outcomes. AB - OBJECTIVE: Anorexia nervosa (AN) is a severe psychiatric illness with little evidence supporting treatment in adults. Among adolescents with AN, family-based treatment (FBT) is considered first-line outpatient approach, with a growing evidence base. However, research on FBT has stemmed from specialist services in research/public health settings. This study investigated the effectiveness of FBT in a case series of adolescent AN treated in a private practice setting. METHOD: Thirty-four adolescents with full or partial AN, diagnosed according to DSM-IV criteria, participated, and were assessed at pretreatment and post-treatment. Assessments included change in % expected body weight, mood, and eating pathology. RESULTS: Significant weight gain was observed from pretreatment to post-treatment. 45.9% of the sample demonstrated full weight restoration and a further 43.2% achieved partial weight-based remission. Missing data precluded an examination of change in mood and ED psychopathology. DISCUSSION: Effective dissemination across different service types is important to the wider availability of evidence-based treatments. These weight restoration data lend preliminary support to the implementation of FBT in real world treatment settings. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1023-1026). PMID- 27270495 TI - Isolation and characterization of primary bone marrow mesenchymal stromal cells. AB - Bone marrow (BM) contains a rare population of mesenchymal stromal cells (MSCs), which have been characterized as nonhematopoietic skeletal progenitor cells with central importance for the hematopoietic microenvironment. Classically, MSCs are isolated by plastic adherence and subsequent culture. However, as cultured stromal cells differ from their in vivo progenitors, it is important to identify the phenotype of the primary MSCs to study these cells in more detail. In the past years, several surface markers have been reported to be suitable for effective enrichment of BM-MSCs, and recent data indicate that the putative MSC stem/progenitor cell population in human adult BM is highly enriched in Lin(-) CD45(-) CD271(+) CD140a (PDGFRalpha)(low/-) cells. Moreover, surface marker combinations have been described for the isolation of MSCs from murine BM. On the basis of these findings, the role of primary MSCs can now be studied in normal and, importantly, diseased BM. Furthermore, genetically engineered mouse models have been developed as powerful tools to investigate well-defined BM stromal cell populations in vivo. Our discussion aims to provide a concise overview of the current state of the art in BM-MSC isolation in humans and briefly present murine MSC isolation approaches and genetic models. PMID- 27270496 TI - Role of CSF3R mutations in the pathomechanism of congenital neutropenia and secondary acute myeloid leukemia. AB - Acquired mutations in the intracellular part of CSF3R (colony stimulating factor 3 receptor, granulocyte) have been detected with a frequency of more than 30% in severe congenital neutropenia (CN) patients. CN is a preleukemic syndrome with a risk of approximately 20% to develop leukemia. More than 80% of CN patients who develop acute myeloid leukemia or myelodysplastic syndrome reveal CSF3R mutations, suggesting that they are involved in leukemogenesis. Using deep sequencing technology, we were able to analyze large cohorts of CN patients for the entire CSF3R sequence as well as to identify cell clones carrying mutations in the intracellular part of CSF3R with very high sensitivity. Acquisition of CSF3R mutations is a CN-specific phenomenon and is associated with inherited mutations causing CN or cyclic neutropenia, such as ELANE mutations. In the group of CN patients negative for known germ-line mutations, biallelic CSF3R mutations were identified. In addition, CSF3R mutant clones are highly dynamic and may disappear and reappear during continuous granulocyte colony-stimulating factor (G CSF) therapy. The time between the first detection of CSF3R mutations and overt leukemia is highly variable. PMID- 27270498 TI - Observational data: Understanding the real MS world. AB - Randomised clinical trials are the primary source of evidence, guiding the use of disease-modifying drugs in multiple sclerosis. However, the spectrum of questions that can be answered in the trial setting is relatively narrow. 'Real-world' observational data analysis has always been the major source of evidence for epidemiology, aetiology, outcomes and prognostics, but is now also increasingly used to study treatment effectiveness. While analyses of observational cohorts typically offer superior power, generalisability and duration of follow-up relative to prospective randomised trials, they are also subject to multiple biases. It is the role of researchers to mitigate bias and to ensure the results of observational studies are robust and valid. In this review of observational data research, we provide an overview of the inherent biases, the available mitigation strategies, and the state and direction of contemporary treatment outcomes research. The review will help clinicians critically appraise published results of observational studies. PMID- 27270497 TI - Altered intestinal permeability in patients with relapsing-remitting multiple sclerosis: A pilot study. AB - BACKGROUND: Alterations of intestinal permeability (IP) may contribute to the pathophysiology of immune-mediated diseases. OBJECTIVE: We investigated the possible association between IP changes and multiple sclerosis (MS). METHODS: We studied 22 patients with relapsing-remitting multiple sclerosis (RRMS) and 18 age and sex-matched healthy donors (HDs), including five twin pairs (one concordant, and four discordant for disease). Measurement of lactulose (L) and mannitol (M; two non-metabolized sugars) levels in urine samples, after an oral load, allowed to quantify gut dysfunction. RESULTS: The proportion of participants with increased IP was significantly higher in patients than in HDs (16/22 (73%) versus 5/18 (28%); p = 0.001). Accordingly, the L/M urinary ratio showed significantly higher values in patients than in controls ( p = 0.0284). Urinary mannitol concentration was significantly lower in patients than in controls ( p = 0.022), suggesting a deficit of absorption from intestinal lumen. Such changes did not appear related to patients' clinical-radiological features. CONCLUSION: The relatively high proportion of IP changes in RR-MS patients seems to confirm our work hypothesis and warrants more work to confirm the result on a larger sample, and to understand the implications for related immunological disturbances and intestinal microbiota alterations. Our finding may also have relevance for oral treatments, recently introduced in clinical practice. PMID- 27270500 TI - Bariatric surgery as an option for diabetes mellitus prevention and treatment in obese persons. AB - Bariatric surgery has been found to be very useful in treating established type-2 diabetes in obese persons, as well as in borderline diabetics, besides giving a good weight loss. Various modifications of the primary bariatric procedures have been introduced, with differ advantages and better efficacy. Good incretin responses from the distal gut give the best results and combining medical treatment are helping patients to get very good glycemic control over a longer term. PMID- 27270499 TI - Effect of Metoclopramide on the Incidence of Early Postoperative Aspiration Pneumonia in Dogs with Acquired Idiopathic Laryngeal Paralysis. AB - OBJECTIVE: Evaluate the effect of a perioperative intravenous continuous rate infusion (CRI) of metoclopramide on the incidence of aspiration pneumonia in the short term postoperative period in dogs undergoing unilateral arytenoid lateralization. STUDY DESIGN: Prospective, randomized, multi-center clinical trial. ANIMALS: 61 client-owned dogs with idiopathic laryngeal paralysis and normal preoperative thoracic radiographs. METHODS: All dogs underwent unilateral arytenoid lateralization with a uniform anesthetic, analgesic, and management protocol. Dogs in the treatment group received an intravenous CRI of metoclopramide for 24 hours perioperative. All dogs were assessed for clinical signs of aspiration pneumonia based on the results of physical examination and owner interview up to the point of suture removal (10-14 days postoperative). Any dog with suspected aspiration pneumonia had thoracic radiographs performed. RESULTS: Six dogs developed aspiration pneumonia in the short term postoperative period (2/28 control dogs and 4/33 treated dogs), accounting for an overall frequency of 10% with no significant difference between control and treated dogs. No variables measured in the study were significantly different between control and treated dogs. CONCLUSIONS: Perioperative metoclopramide, at the doses used in this study, did not affect the incidence of aspiration pneumonia in the short term postoperative period in dogs with idiopathic laryngeal paralysis undergoing unilateral arytenoid lateralization. PMID- 27270501 TI - Association of leptin with orthostatic blood pressure changes in Parkinson's disease. AB - INTRODUCTION: Leptin is involved in the regulation of blood pressure; however, no studies have evaluated the role of leptin in blood pressure changes during orthostatic stress in PD patients. The aim of this study was to determine whether plasma leptin levels influence orthostatic blood pressure changes in PD patients. METHODS: We enrolled 55 patients and 25 age-matched healthy controls in this study. Associations between head-up tilt test measurements and leptin levels were evaluated. RESULTS: Systolic blood pressure changes during the head-up tilt tests were strongly correlated with leptin levels at baseline and at a 60-degree head up tilt in PD patients, but not in control subjects. Multiple regression analysis also demonstrated that leptin levels were associated with orthostatic blood pressure changes. CONCLUSION: These observations suggest that low leptin levels may be associated with orthostatic hypotension during the head-up tilt test in patients with PD. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27270503 TI - Acinetobacter baumannii: biology and drug resistance - role of carbapenemases. AB - Acinetobacter baumannii is a Gram-negative, glucose-non-fermenting, oxidase negative coccobacillus, most commonly associated with the hospital settings. The ability to survive in adverse environmental conditions as well as high level of natural and acquired antimicrobial resistance make A. baumannii one of the most important nosocomial pathogens. While carbapenems have long been considered as antimicrobials of last-resort, the rates of clinical A. baumannii strains resistant to these antibiotics are increasing worldwide. Carbapenem resistance among A. baumannii is conferred by coexisting mechanisms including: decrease in permeability of the outer membrane, efflux pumps, production of beta-lactamases, and modification of penicillin-binding proteins. The most prevalent mechanism of carbapenem resistance among A. baumannii is associated with carbapenem-hydro lysing enzymes that belong to Ambler class D and B beta-lactamases. In addition, there have also been reports of resistance mediated by selected Ambler class A carbapenemases among A. baumannii strains. Resistance determinants in A. baumannii are located on chromosome and plasmids, while acquisition of new mechanisms can be mediated by insertion sequences, integrons, transposons, and plasmids. Clinical relevance of carbapen-em resistance among strains isolated from infected patients, carriers and hospital environment underlines the need for carbapenemase screening. Currently available methods vary in principle, accuracy and efficiency. The techniques that deserve particular attention belong to both easily accessible unsophisticated methods as well as advanced techniques based on mass spectrometry or molecular biology. While carbapenemases limit the therapeutic options in A. baumannii infections, studies concerning novel beta lactamase inhibitors offer a new insight into effective therapy. PMID- 27270502 TI - Kif14 overexpression accelerates murine retinoblastoma development. AB - The mitotic kinesin KIF14 has an essential role in the recruitment of proteins required for the final stages of cytokinesis. Genomic gain and/or overexpression of KIF14 has been documented in retinoblastoma and a number of other cancers, such as breast, lung and ovarian carcinomas, strongly suggesting its role as an oncogene. Despite evidence of oncogenic properties in vitro and in xenografts, Kif14's role in tumor progression has not previously been studied in a transgenic cancer model. Using a novel Kif14 overexpressing, simian virus 40 large T-antigen retinoblastoma (TAg-RB) double transgenic mouse model, we aimed to determine Kif14's role in promoting retinal tumor formation. Tumor initiation and development in double transgenics and control TAg-RB littermates were documented in vivo over a time course by optical coherence tomography, with subsequent ex vivo quantification of tumor burden. Kif14 overexpression led to an accelerated initiation of tumor formation in the TAg-RB model and a significantly decreased tumor doubling time (1.8 vs. 2.9 weeks). Moreover, overall percentage tumor burden was also increased by Kif14 overexpression. These data provide the first evidence that Kif14 can promote tumor formation in susceptible cells in vivo. PMID- 27270504 TI - The influence of anti-TNF therapy on CD31 and VEGF expression in colonic mucosa of Crohn's disease patients in relation to mucosal healing. AB - INTRODUCTION: Immune-mediated angiogenesis may play an important role in the pathogenesis of inflammatory lesions in Crohn's disease (CD). The study aimed to assess the influence of anti-tumour necrosis factor (anti-TNF) therapy on the angiogenesis in relation to microscopic and endoscopic healing in CD patients. MATERIAL AND METHODS: Colonic tissue samples from 17 CD patients were taken during colonoscopy before and after anti-TNF therapy. Endoscopic and microscopic severities were estimated using validated scores. Immunohistochemical expression of CD31 and vascular endothelial growth factor (VEGF) were assessed in parallel. RESULTS: The expression of CD31 and VEGF decreased significantly after the anti TNF therapy in parallel to endoscopic improvement; however, the microscopic activity did not change significantly. There was a correlation between the change in CD31 and VEGF expression (p = 0.01; r = 0.6), as well as endoscopic healing (p = 0.04; r = 0.4). CD31 immunoexpression correlated with the number of poly- and mononuclear cells in the infiltrates in the mucosal lamina propria before the therapy (p = 0.02; r = 0.5). CONCLUSIONS: We suggest that modulation of vascular proliferation can be a novel option to increase the efficacy of biological therapy in CD. PMID- 27270505 TI - In vitro culture of primary human myoblasts by using the dextran microcarriers Cytodex3(r). AB - INTRODUCTION: Primary cells in vitro culture scale-up is a crucial issue in cell based tissue and organ regeneration therapy. Reducing costs and space occupied by the cells cultured in vitro has been an important target. Cells cultured in vitro with the use of bioreactor with dextran microcarriers (Cytodex(r)) have potentially a chance to meet many of the cell therapy requirements. MATERIAL AND METHODS: We used collagen-coated carriers (Cytodex3(r)) and a spinner flask bioreactor to develop environment suitable for human myoblast proliferation. In parallel, standard adherent in vitro culture conditions for myoblasts propagation (T-flask) were conducted. Cell cycle characterization, senescence, myogenic gene ex-pression and cell apoptosis were evaluated in order to find differences between two culture systems under study. RESULTS: The number of cells obtained in bioreactor per 106 of starting cells population was approximately ten times lower in comparison with T-flask culture system. The microcarriers cultured adult myoblasts in compari-son with the regular T-flask culture showed faster and more advanced replicative aging and lower proliferative potential. Moreover, the percentage of the cells that entailed an irreversible cell arrest (G0 phase) was also significantly (p < 0.0001) increased. CONCLUSIONS: Our results suggest that population of primary human myoblasts obtained from adult individuals and propagated on dextran microcarriers did not meet the requirements of the regenerative medicine regarding quantity and quality of the cells obtained. Nonetheless, further optimization of the cell scaling up process including both microcarriers and/or bioreactor program is still an important option. PMID- 27270506 TI - Anticipatory Manoeuvres in Bird Flight. AB - It is essential for birds to be agile and aware of their immediate environment, especially when flying through dense foliage. To investigate the type of visual signals and strategies used by birds while negotiating cluttered environments, we presented budgerigars with vertically oriented apertures of different widths. We find that, when flying through narrow apertures, birds execute their maneuvers in an anticipatory fashion, with wing closures, if necessary, occurring well in advance of the aperture. When passing through an aperture that is narrower than the wingspan, the birds close their wings at a specific, constant distance before the aperture, which is independent of aperture width. In these cases, the birds also fly significantly higher, possibly pre-compensating for the drop in altitude. The speed of approach is largely constant, and independent of the width of the aperture. The constancy of the approach speed suggests a simple means by which optic flow can be used to gauge the distance and width of the aperture, and guide wing closure. PMID- 27270508 TI - Management of a new pregnancy in a woman with chronic hypertension. PMID- 27270507 TI - Genetic variations associated with six-white-point coat pigmentation in Diannan small-ear pigs. AB - A common phenotypic difference among domestic animals is variation in coat color. Six-white-point is a pigmentation pattern observed in varying pig breeds, which seems to have evolved through several different mechanistic pathways. Herein, we re-sequenced whole genomes of 31 Diannan small-ear pigs from China and found that the six-white-point coat color in Diannan small-ear pigs is likely regulated by polygenic loci, rather than by the MC1R locus. Strong associations were observed at three loci (EDNRB, CNTLN, and PINK1), which explain about 20 percent of the total coat color variance in the Diannan small-ear pigs. We found a mutation that is highly differentiated between six-white-point and black Diannan small-ear pigs, which is located in a conserved noncoding sequence upstream of the EDNRB gene and is a putative binding site of the CEBPB protein. This study advances our understanding of coat color evolution in Diannan small-ear pigs and expands our traditional knowledge of coat color being a monogenic trait. PMID- 27270509 TI - Development of the American Society of Colon and Rectal Surgeons' Rectal Cancer Surgery Checklist. PMID- 27270510 TI - Clinical Practice Guidelines for Colon Volvulus and Acute Colonic Pseudo Obstruction. PMID- 27270511 TI - Development of The American Society of Colon and Rectal Surgeons' Rectal Cancer Surgery Checklist. AB - BACKGROUND: There is excellent evidence that surgical safety checklists contribute to decreased morbidity and mortality. OBJECTIVE: The purpose of this study was to develop a surgical checklist composed of the key phases of care for patients with rectal cancer. DESIGN: A consensus-oriented decision-making model involving iterative input from subject matter experts under the auspices of The American Society of Colon and Rectal Surgeons was designed. SETTINGS: The study was conducted through meetings and discussion to consensus. PATIENTS: Patient data were extracted from an initial literature review. MAIN OUTCOME MEASURES: The checklist was measured by its ability to improve care in complex rectal surgery cases by reducing the possibility of omission through the division of treatment into 3 distinct phases. RESULTS: The process generated a 25-item checklist covering the spectrum of care for patients with rectal cancer who were undergoing surgery. LIMITATIONS: The study was limited by its lack of prospective validation. CONCLUSIONS: The American Society of Colon and Rectal Surgeons rectal cancer surgery checklist is composed of the essential elements of preoperative, intraoperative, and postoperative care that must be addressed during the surgical treatment of patients with rectal cancer. PMID- 27270512 TI - Robot-Assisted Abdominoperineal Resection: Clinical, Pathologic, and Oncologic Outcomes. AB - BACKGROUND: The extralevator approach to abdominoperineal resection is associated with a decreased incidence of rectal perforation and circumferential resection margin positivity translating to lower recurrence rates. The abdominoperineal resection, as such, is an operation associated with poorer outcomes in comparison with low anterior resections, and any improvements in short-term outcomes are likely to be related to surgical technique. Robot assistance in extralevator abdominoperineal resection has shown improvement in these pathologic outcomes. Because these are surrogate markers for local recurrence and disease-free survival, long-term survival data are needed to assess the efficacy of this robot assisted technique, exclusively in a dedicated abdominoperineal resection cohort. OBJECTIVE: We assessed the perioperative, pathologic, and oncologic outcomes of the robot-assisted extralevator abdominoperineal resection for rectal cancer. DESIGN: This study was a review of a prospective database of patients over a 5 year period. SETTING: Procedures were performed in the colorectal division of a tertiary hospital from April 2007 to July 2012. PATIENTS: Patients with rectal cancer were operated on robotically. Indications for abdominoperineal resection were low rectal cancers invading the sphincter complex or location in the anal canal precluding anastomosis. INTERVENTIONS: All patients received a robot assisted extralevator abdominoperineal resection. MAIN OUTCOME MEASURES: Operative and perioperative measures, pathologic outcomes, and disease-free survival and overall survival were documented and assessed. RESULTS: Twenty-two patients (15 men) with a mean age of 65.5 years and mean BMI of 28.6 kg/m underwent robotic abdominoperineal resection. Circumferential resection margin was positive in 13.6%. There was 1 tumor/rectal perforation. At a mean follow-up of 33.9 months, overall survival was 81.8% with a disease-free survival of 72.7%. Local recurrence was 4.5%. LIMITATIONS: This was a single-institution study with no comparative open or laparoscopic group. CONCLUSION: Robot-assisted abdominoperineal resection is safe, feasible, and oncologically sound with short term and long-term outcomes comparable to open and laparoscopic surgery. PMID- 27270513 TI - Intraperitoneal-Free Cancer Cells Represent a Major Prognostic Factor in Colorectal Peritoneal Carcinomatosis. AB - BACKGROUND: Intraperitoneal-free cancer cells are considered as an important prognostic tool in gastric and ovarian cancer. However, their significance in colorectal cancer remains more controversial. OBJECTIVE: This study aimed to determine the role of intraperitoneal-free cancer cells as a prognostic tool in the outcome in colorectal peritoneal carcinomatosis treated with curative intent by complete cytoreductive surgery. DESIGN: This study is an analysis of a prospectively maintained database. PATIENTS: Between 1991 and 2012, all patients treated in a single institution for colorectal peritoneal carcinomatosis by complete cytoreductive surgery with peritoneal cytology available were evaluated. Peritoneal cytology was stained in the conventional way (May Grumwald Giemsa). RESULTS: Among a population of 162 patients treated for colorectal peritoneal carcinomatosis by complete cytoreductive surgery, 38 presented positive intraperitoneal-free cancer cells (23.5%). Systemic chemotherapy was administered to 135 patients (85%) during the preoperative course. Median follow-up was 34.5 months. Median overall survival was 19 and 44 months for positive and negative intraperitoneal-free cancer cells (p = 0.018). In multivariate analysis, Peritoneal Carcinomatosis Index and positive intraperitoneal-free cancer cells were significant prognostic factors of overall survival (HR, 2.3 (1.18-4.52), p = 0.014; HR, 1.9 (1.08-3.38), p = 0.027). LIMITATIONS: Retrospective analysis and the long period were limitations of study. CONCLUSION: Along with the Peritoneal Carcinomatosis Index, intraperitoneal-free cancer cells are a strong prognostic factor for patients treated with curative intent for colorectal peritoneal carcinomatosis by complete cytoreductive surgery. The presence of intraperitoneal free cancer cells should lead to the consideration of different treatment strategies such as extensive intraperitoneal lavage, targeted intraperitoneal therapies, or repeated intraperitoneal chemotherapy. PMID- 27270514 TI - National Early Rectal Cancer Treatment Revisited. AB - BACKGROUND: Treatment of early stage rectal cancer has excellent oncological results. To reduce treatment-related mortality and morbidity and improve functional results, a focus on local resections is increasingly important. OBJECTIVE: The purpose of this study was to compare outcomes after transanal endoscopic microsurgery and total mesorectal excision for early stage rectal cancer (T1 + T2) in Norway. DESIGN: This was an observational study based on prospective data from the Norwegian Colorectal Cancer Registry. SETTINGS: The study was conducted as a national, population-based study. PATIENTS: All 543 patients with T1 and 1593 patients with T2 rectal cancer without distant metastases that was treated by transanal endoscopic microsurgery or total mesorectal excision without radiochemotherapy during 2000-2009 were included. MAIN OUTCOME MEASURES: The primary outcomes were 5-year relative survival and 5 year local recurrence rate. RESULTS: Among 543 patients with T1 cancer, the 5 year overall survival rate was 65.3% after transanal endoscopic microsurgery versus 81.5% after total mesorectal excision (p = 0.012). Adjusted for age and sex there was no excess mortality for transanal endoscopic microsurgery (HR = 1.28 (95% CI, 0.8-1.9); p = 0.22). The 5-year relative survival rate was 96.8% after transanal endoscopic microsurgery versus 98.2% after total mesorectal excision (p = 0.603), and the 5-year local recurrence rate was 14.5% versus 1.4% (p < 0.001). Among 1593 patients with T2 cancer, 5-year overall survival was 42.1% versus 76.1% (p < 0.001), 5-year relative survival was 65.4% versus 93.9% (p < 0.001), and 5 year local recurrence rate was 11.4% versus 4.4% in the 2 groups. LIMITATIONS: The study is limited by its observational design and that the 2 groups were different according to patient and tumor characteristics. Another limitation was the low number of transanal endoscopic microsurgery procedures. CONCLUSIONS: Transanal endoscopic microsurgery had comparable 5-year relative survival to total mesorectal excision in T1 rectal cancer but inferior 5 year relative survival in T2 rectal cancer. Transanal endoscopic microsurgery was associated with higher local recurrence rates for both T1 and T2 tumors. PMID- 27270515 TI - Operative Method for Transverse Colon Carcinoma: Transverse Colectomy Versus Extended Colectomy. AB - BACKGROUND: The type of surgery performed for primary transverse colon cancer varies based on tumor characteristics and surgeon perspective. The optimal oncological outcome following different surgical options has not been clearly established, and transverse colectomy has shown oncological equivalence only in small cohort studies. OBJECTIVE: Our aim was to compare long-term oncological outcomes after transverse colectomy versus extended resection for transverse colon cancer. DESIGN: This study is a retrospective review of prospectively collected data. SETTING: This study was conducted at a tertiary care hospital. METHOD: All patients treated for transverse colon cancer at the Samsung Medical Center between 1995 and 2013 were included. MAIN OUTCOME MEASURES: Oncological outcomes were compared between 2 groups of patients: a transverse colectomy group and an extended colectomy group (which included extended right hemicolectomy and left hemicolectomy). RESULTS: A total of 1066 patients were included, of whom 750 (70.4%) underwent extended right hemicolectomy, 127 (11.9%) underwent transverse colectomy, and 189 (17.7%) underwent left hemicolectomy. According to univariate analysis, surgical approach, histological type, tumor morphology, cancer T and N stage, cancer size, and lymphovascular invasion were significant factors contributing to disease-free survival (DFS). However, as seen in multivariate analysis, only node-positive disease (HR = 2.035 (1.188-3.484)), tumors with ulcerative morphology (HR = 3.643 (1.132-11.725)), and the presence of vascular invasion (HR = 2.569 (1.455-4.538)) were significant factors for DFS. Further analysis with a propensity-matched cohort between the transverse and extended colectomy groups demonstrated no significant differences in DFS and overall survival. LIMITATIONS: This study was limited because it was performed at a single institution and it was retrospective in nature. CONCLUSION: In terms of perioperative and oncological outcomes, transverse colectomy and extended colectomy did not differ despite a shorter specimen length and fewer lymph nodes harvested in the transverse colectomy group. Independent prognostic factors for DFS were node-positive disease, the presence of vascular invasion, and ulcerative morphology. PMID- 27270516 TI - Dual-Energy CT of Rectal Cancer Specimens: A CT-based Method for Mesorectal Lymph Node Characterization. AB - BACKGROUND: An accurate method to assess malignant lymph nodes in the mesorectum is needed. Dual-energy CT scans simultaneously with 2 levels of energy and thereby provides information about tissue composition based on the known effective Z value of different tissues. Each point investigated is represented by a certain effective Z value, which allows for information on its composition. OBJECTIVE: We wanted to standardize a method for dual-energy scanning of rectal specimens to evaluate the sensitivity and specificity of benign versus malignant lymph node differentiation. Histopathological evaluation of the nodes was our reference. DESIGN: This was a descriptive and prospective study. SETTINGS: Seventeen rectal specimens were examined in 2 series. The first series was conducted with 3 specimens from patients who were not given perioperative contrast; 3 had iodine-based contrast and 3 had gadolinium-based contrast. We concluded that iodine was the contrast agent of choice and therefore included 8 more patients in a second series, given iodine-based contrast, for further analysis. PATIENTS: Quantitative imaging data were collected from 197 individual lymph nodes from 17 specimens, from patients with rectal cancer. MAIN OUTCOME MEASURES: We measured accuracy of differentiating benign from malignant lymph nodes by investigating the following: 1) gadolinium, iodine, and water concentrations in lymph nodes; 2) dual-energy ratio; 3) dual-energy index; and 4) effective Z value. RESULTS: Optimal discriminations between benign and malignant lymph nodes were obtained using the following cutoff values: 1) effective Z at 7.58 (sensitivity, 100%; specificity, 90%; and accuracy, 93%), 2) dual-energy ratio at 1.0 * 10 (sensitivity, 96%; specificity, 87%; and accuracy, 90%), 3) dual-energy index at 0.03 (sensitivity, 97%; specificity, 88%; and accuracy, 91%), and 4) iodine concentration at 2.58 MUg/mL (sensitivity, 86%; specificity, 92%; and accuracy, 89%). LIMITATIONS: The investigation is conducted on isolated surgical specimens from rectal cancer operations. CONCLUSIONS: Dual-energy CT can be performed on rectal specimens. The discrimination between benign and malignant nodes seems promising when using iodine as contrast. PMID- 27270517 TI - Diverticular Abscess Managed With Long-term Definitive Nonoperative Intent Is Safe. AB - BACKGROUND: Initial nonoperative management of diverticular abscess has become the standard of care; however, the need for elective resection after this index episode is unclear. OBJECTIVE: The purpose of this study was to assess the long term outcomes of expectant management after initial nonoperative treatment of diverticular abscess. DESIGN: This was a retrospective chart review with prospective telephone follow-up of patients. SETTINGS: The study was conducted at a large tertiary academic colorectal surgery practice in Canada. PATIENTS: Adult patients with CT-documented acute sigmoid diverticulitis complicated by abscess managed nonoperatively from 2000 to 2013 were included. INTERVENTIONS: Long-term definitive nonoperative management of diverticular abscess. MAIN OUTCOME MEASURES: The primary outcome was emergency sigmoidectomy or death from recurrent diverticulitis. Secondary outcomes were recurrent diverticulitis and elective sigmoidectomy for diverticulitis. RESULTS: Of 135 patients with acute diverticulitis complicated by abscess, a total of 73 patients were managed with nonoperative intent and long-term expectant management. The median follow-up was 62 (Q1 to Q3: 28-98) months. After resolution of the index episode, 22 patients [30.1% (95% CI, 19.6%-40.6%)] experienced a recurrent episode of diverticulitis at a median of 23 (range, 9-40) months. Two patients [2.7% (95% CI, -1.0% to 6.4%)] had a recurrent episode with peritonitis that required sigmoidectomy with stoma at 6 and 64 months. Both patients underwent reversal after 4 and 8 months. Seven [9.6% (95% CI, 2.8%-16.4%)] patients experienced a complicated recurrence and underwent an elective sigmoidectomy [median time to colectomy, 33 (range, 16 56) months]. Thirteen patients [17.8% (95% CI, 9.0%-26.6%)] experienced an uncomplicated recurrence, all of whom were managed with continued nonoperative intent [median follow-up, 81 (range, 34-115) months]. No mortality occurred. On multivariate logistic regression, female gender (p = 0.048) and a previous episode of uncomplicated diverticulitis before the index diverticular abscess (p = 0.020) were associated with a recurrent episode. LIMITATIONS: This study was limited by its retrospective design and modest sample size. CONCLUSIONS: After initial successful nonoperative management of diverticulitis with abscess, expectant management with nonoperative intent is a safe long-term option with low rates of surgery, especially in the emergency setting. See Video, Supplemental Digital Content 1, on the nonoperative management of diverticular abscess at http://links.lww.com/DCR/A234. PMID- 27270518 TI - Do Appendicitis and Diverticulitis Share a Common Pathological Link? AB - OBJECTIVE: The aim of this study was to determine whether there is an association between appendicitis and diverticulitis. DESIGN: This study is a retrospective cohort analysis. SETTING: This study was conducted in a subspecialty practice at a tertiary care facility. PATIENTS: We examined the rate of appendectomy among 4 cohorts of patients: 1) patients with incidentally identified diverticulosis on screening colonoscopy, 2) inpatients with medically treated diverticulitis, 3) patients who underwent left-sided colectomy for diverticulitis, and 4) patients who underwent colectomy for left-sided colorectal cancer. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: The primary outcome measured was the appendectomy rate. RESULTS: We studied a total of 928 patients in this study. There were no differences in the patient characteristics of smoking status, nonsteroidal use, or history of irritable bowel syndrome across the 4 study groups. Patients with surgically treated diverticulitis had significantly more episodes of diverticulitis (2.8 +/- 1.9) than the medically treated group (1.4 +/ 0.8) (p < 0.0001). The rate of appendectomy was 8.2% for the diverticulosis control group, 13.5% in the cancer group, 23.5% in the medically treated diverticulitis group, and 24.5% in the surgically treated diverticulitis group (p < 0.0001). After adjusting for demographics and other clinical risk factors, patients with diverticulitis had 2.8 times higher odds of previous appendectomy (p < 0.001) than the control groups. LIMITATIONS: The retrospective study design is associated with selection, documentation, and recall bias. CONCLUSIONS: Our data reveal significantly higher appendectomy rates in patients with a diagnosis of diverticulitis, medically or surgically managed, in comparison with patients with incidentally identified diverticulosis. Therefore, we propose that appendicitis and diverticulitis share similar risk factors and potentially a common pathological link. PMID- 27270519 TI - Colorectal Surgery Outcomes in Chronic Dialysis Patients: An American College of Surgeons National Surgical Quality Improvement Program Study. AB - BACKGROUND: More than 450,000 US patients with end-stage renal disease currently dialyze. The risk of morbidity and mortality for these patients after colorectal surgery has been incompletely described. OBJECTIVE: We analyzed the 30-day morbidity and mortality rates of chronic dialysis patients who underwent colorectal surgery. DESIGN: This was a retrospective analysis. SETTINGS: Hospitals that participate in the American College of Surgeons National Surgical Quality Improvement Program were included. PATIENTS: The study included adult patients who underwent emergency or elective colon or rectal resection between 2009 and 2014. MAIN OUTCOME MEASURES: Baseline characteristics were compared by dialysis status. The impact of chronic dialysis on 30-day mortality and serious postoperative morbidity was examined using multivariate logistic regression. RESULTS: We identified 128,757 patients who underwent colorectal surgery in the American College of Surgeons National Surgical Quality Improvement Program database. Chronic dialysis patients accounted for 1% (n = 1285) and were more likely to be older (65.4 vs 63.2 years; p < 0.0001), black (27.2% vs 8.7%; p < 0.0001), preoperatively septic (22.1% vs 7.1%; p < 0.0001), require emergency surgery (52.0% vs 14.7%; p < 0.0001), have ischemic bowel (15.7% vs 1.6%; p < 0.0001), or have perforation/peritonitis (15.5% vs 4.2%; p < 0.0001). Chronic dialysis patients were also less likely to have a laparoscopic procedure (17.3% vs 45.0%; p < 0.0001). Chronic dialysis patients had higher unadjusted mortality (22.4% vs 3.3%; p < 0.0001), serious postoperative morbidity (47.9% vs 18.8%; p < 0.0001), and median length of stay (9 vs 6 days; p < 0.0001). In emergent cases (n = 19,375), multivariate logistic regression models demonstrated a higher risk of mortality for dialysis patients (OR = 1.73 (95% CI, 1.38-2.16)) but not for serious morbidity. Models for elective surgery demonstrated a similar effect on mortality (OR = 2.47 (95% CI, 1.75-3.50)) but also demonstrated a higher risk of serious morbidity (OR = 1.28 (95% CI, 1.04-1.56)). LIMITATIONS: The postoperative 30-day window may underestimate the true incidence of serious morbidity and mortality. CONCLUSIONS: Chronic dialysis patients undergoing elective or emergent colorectal procedures have a higher risk-adjusted mortality. PMID- 27270521 TI - Patient Comorbidity and Serious Adverse Events after Outpatient Colonoscopy: Population-based Study From Three States, 2006 to 2009. AB - BACKGROUND AND OBJECTIVE: Serious GI adverse events in the outpatient setting were examined for patients with a full spectrum of comorbid conditions and combinations of multiple comorbidities. DESIGN: This is a retrospective follow-up study. SETTING: Ambulatory surgery and hospital discharge data sets from California, Florida, and New York, 2006 to 2009, were used. PATIENTS: The outpatient colonoscopies of 4,234,084 adults aged 19 to 85 and over and payers were examined. MAIN OUTCOME: Thirty-day hospitalizations due to colonic perforations and GI bleeding, measured as cumulative outcomes, were investigated. RESULTS: About 24% of patients undergoing outpatient colonoscopy had a comorbid condition. In comparison with patients without comorbidities, the adjusted risks of adverse events were greater for patients with several single comorbidities and combinations of multiple comorbid conditions. Elderly patients and those treated in freestanding Ambulatory Surgery Centers had higher odds of colonic perforations and GI bleeding than younger patients and patients treated in hospital outpatient departments. LIMITATION: The study was constrained by limitations inherent in administrative data. CONCLUSIONS: Given the large number of outpatient colonoscopies performed in the United States, these procedures should be provided with caution to patients with chronic and multiple comorbidities and the elderly, because these populations are associated with higher rates of colonic perforations and GI bleeding. PMID- 27270520 TI - Should Immunomodulation Therapy Alter the Surgical Management in Patients With Rectovaginal Fistula and Crohn's Disease? AB - BACKGROUND: Rectovaginal fistula in Crohn's disease is challenging for both healthcare providers and patients. The impact of immunomodulation therapy on healing after surgery is unclear. OBJECTIVE: The purpose of this study was to examine whether immunomodulation therapy impacts healing after surgery for rectovaginal fistula in Crohn's disease. DESIGN: This was a retrospective analysis with a follow-up telephone survey. SETTINGS: The study was conducted at two major tertiary referral centers. PATIENTS: All of the patients who underwent rectovaginal fistula repair from 1997 to 2013 at our centers were included. MAIN OUTCOME MEASURES: A chi test and logistical regression analysis were used to study treatment outcomes according to type of procedure, recent use of immunosuppressives, and number of previous attempted repairs. Age, BMI, smoking, comorbidities, previous vaginal delivery/obstetric injury, use of probiotics, diverting stoma, and use of seton were also analyzed. RESULTS: A total of 120 (62%) patients were contacted, and 99 (51%) of them agreed to participate in the study. Mean follow-up after surgical repair was 39 months. Procedures included advancement flap (n = 59), transvaginal repair (n = 14), muscle interposition (n = 14), episioproctotomy (n = 6), sphincteroplasty (n = 3), and other (n = 3); overall, 63% of patients experienced healing. Sixty-eight patients underwent recent immunomodulation therapy but did not exhibit statistical significance in outcome after surgical repair. In the subset of patients with fistula related to obstetric injury, a 74% (n = 26) healing rate after surgical repair was observed. Age, BMI, diabetes mellitus, use of steroids, probiotics, seton before repair, fecal diversion, and number of repairs did not affect healing. LIMITATIONS: This was a retrospective analysis; the high volume tertiary referral inflammatory bowel disease centers studied may not be reflective of rectovaginal fistula presentation, treatment, or results in all patients, and the 3-year follow-up may not be sufficiently long. CONCLUSIONS: Despite a relatively low success rate (63%) in healing after surgical repair of a rectovaginal fistula, the recent use of immunomodulation therapy did not negatively impact healing. However, tissue interposition techniques had the highest success rates. PMID- 27270522 TI - Systematic Review and Meta-Analysis of Extraperitoneal Versus Transperitoneal Colostomy for Preventing Parastomal Hernia. AB - BACKGROUND: Parastomal hernia remains a frequent problem after constructing a colostomy. Current research mainly focuses on prophylactic mesh placement as an addition to transperitoneal colostomies. However, for constructing a colostomy, either an extraperitoneal or transperitoneal route can be chosen. OBJECTIVE: The aim of this meta-analysis was to investigate which technique results in lower parastomal hernia rates in patients undergoing end colostomy. DATA SOURCES: A meta-analysis was conducted according to Preferred Items for Reporting of Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Embase, MEDLINE, Web of Science, Scopus, Cumulative Index to Nursing and Allied Health Literature, Cochrane, PubMed, and Google Scholar databases were searched. The study protocol was registered in the International Prospective Register of Systematic Reviews database. STUDY SELECTION: Studies comparing extraperitoneal and transperitoneal colostomies were included. Only studies written in English were included. The quality of studies and risk of bias were assessed using the Cochrane risk-of-bias tool. The quality of nonrandomized studies was assessed using the Newcastle-Ottawa Scale. INTERVENTION: The intervention was colostomy formation. MAIN OUTCOME MEASURES: The main outcome measure was parastomal hernia incidence. Secondary outcome measures were stoma prolapse, stoma necrosis, and operating time. RESULTS: Of 401 articles found, a meta-analysis was conducted of 10 studies (2 randomized controlled trials and 8 retrospective studies) composed of 1048 patients (347 extraperitoneal and 701 transperitoneal). Extraperitoneal colostomy led to significantly lower parastomal hernia rates (22 of 347 (6.3%) for extraperitoneal versus 125 of 701 (17.8%) for transperitoneal; risk ratio = 0.36 (95% CI, 0.21 0.62); I = 26%; p < 0.001) and significantly lower stoma prolapse rates (2 of 185 (1.1%) for extraperitoneal versus 13 of 179 (7.3%) for transperitoneal; risk ratio = 0.21 (95% CI, 0.06-0.73); I = 0%; p = 0.01). Differences in stoma necrosis were not significant. Operating time data were insufficient to analyze. LIMITATIONS: Most of the studies were nonrandomized, and some were not recent publications. CONCLUSIONS: Although the majority of studies included were retrospective, extraperitoneal colostomy was observed to lead to a lower rate of parastomal hernia and stoma prolapse. PMID- 27270523 TI - Postdefecation Cleansing Methods: Tissue Paper or Water? An Analytical Review. PMID- 27270524 TI - Fluorescence Imaging in Anorectal Advancement Flaps. PMID- 27270525 TI - Real-Time Indocyanine Green Fluorescence Imaging-Guided Complete Mesocolic Excision in Laparoscopic Flexural Colon Cancer Surgery. AB - INTRODUCTION: Laparoscopic surgery for colon cancer located in the hepatic flexure or splenic flexure is not standardized, because lymphatic drainage at this site may vary and the precise site of lymphatic dissection is uncertain. TECHNIQUE: Indocyanine green was injected into the submucosal layer around the tumor at 2 points with a 23-gauge localized injection before lymph node dissection and the lymph flow was observed using a near-infrared camera system 30 minutes after injection. In addition, a complete mesocolic excision with central vascular ligation guided the region where the lymph flow was fluorescently observed. RESULTS: A total of 20 consecutive patients (hepatic flexure, 10 patients; splenic flexure, 10 patients) were enrolled in this study. All of the procedures were safely performed without any complications. The lymph flow was visualized in 19 patients (95%) intraoperatively. Modification of the operative methods was required for 5 patients (modification in the separation line of the mesocolon and vessel selection for central vascular ligation) because the area of lymph flow observed during surgery differed from that of the preoperative diagnosis. CONCLUSION: Intraoperative real-time visualization of the lymph flow using indocyanine green fluorescence imaging during laparoscopic colon cancer surgery, especially flexural colon cancer surgery, is feasible and a helpful technique for identifying appropriate central vessels to be dissected and for determining an appropriate separation line of the mesentery. PMID- 27270526 TI - Requiem on the Deep Postanal Space and Supralevator Abscesses. PMID- 27270527 TI - Asymptomatic Radiologic Recurrence of Rectoanal Intussusception After Laparoscopic Ventral Rectopexy: Is it Relevant? PMID- 27270528 TI - Transanal Total Mesorectal Excision: Save the Nerves and Urethra. PMID- 27270531 TI - Determinants and Equity Evaluation for Health Expenditure Among Patients with Rare Diseases in China. AB - BACKGROUND: China has not established social security system for rare diseases. Rare diseases could easily impoverish patients and their families. Little research has studied the equity and accessibility of health services for patients with rare diseases in China. This study aimed to explore the factors that influence health expenditure of rare diseases and evaluate its equity. METHODS: Questionnaire survey about living conditions and cost burden of patients with rare diseases was conducted. Individual and family information, health expenditure and reimbursement in 2014 of 982 patients were collected. The impact of medical insurance, individual sociodemographic characteristics, family characteristics, and healthcare need on total and out-of-pocket (OOP) health expenditures was analyzed through the generalized linear model. Equity of health expenditure was evaluated by both concentration index and Lorenz curve. RESULTS: Of all the surveyed patients, 11.41% had no medical insurance and 92.10% spent money to seek medical treatment in 2014. It was suggested female (P = 0.048), over 50 years of age (P = 0.062), high-income group (P = 0.021), hospitalization (P = 0.000), and reimbursement ratio (RR) (P = 0.000) were positively correlated with total health expenditure. Diseases not needing long-term treatment (P = 0.000) was negatively correlated with total health expenditure. Over 50 years of age (P = 0.065), high-income group (P = 0.018), hospitalization (P = 0.000) and having Urban Employee Basic Medical Insurance (UEBMI) (P = 0.022) were positively correlated with OOP health expenditure. Patient or the head of the household having received higher education (P = 0.044 and P = 0.081) and reimbursement ratio (P = 0.078) were negatively correlated with OOP health expenditure. The equity evaluation found concentration indexes of health expenditure before and after reimbursement were 0.0550 and 0.0539, respectively. CONCLUSIONS: OOP health expenditure of patients with UEBMI was significantly more than that of patients without medical insurance. However, for any other medical insurance, there was no difference between OOP health expenditure of the insured patients and patients without insurance. The current reimbursement policies have increased the equity of health expenditure, but are biased toward high-income people. PMID- 27270532 TI - Overlap between Headache, Depression, and Anxiety in General Neurological Clinics: A Cross-sectional Study. AB - BACKGROUND: Many studies have reported that depression and anxiety have bidirectional relationship with headache. However, few researches investigated the roles of depression or anxiety in patients with headache. We surveyed the prevalence of depression and anxiety as a complication or cause of headache among outpatients with a chief complaint of headache at neurology clinics in general hospitals. Additional risk factors for depression and anxiety were also analyzed. METHODS: A cross-sectional study was conducted at 11 general neurological clinics. All consecutive patients with a chief complaint of headache were enrolled. Diagnoses of depression and anxiety were made using the Chinese version of the Mini International Neuropsychiatric Interview, and those for headache were made according to the International Classification of Headache Disorders, 2nd Edition. The headache impact test and an 11-point verbal rating scale were applied to assess headache severity and intensity. Logistic regression was used to analyze risk factors of patients with headache for depression or anxiety. RESULTS: A total of 749 outpatients with headache were included. Among them, 148 (19.7%) were diagnosed with depression and 103 (13.7%) with anxiety. Further analysis showed that 114 (15.2%) patients complaining headache due to somatic symptoms of psychiatric disorders and 82 (10.9%) had a depression or anxiety comorbidity with headache. Most patients with depression or anxiety manifested mild to moderate headaches. Poor sleep and severe headache-related disabilities were predictors for either depression or anxiety. CONCLUSION: Clinicians must identify the etiology of headache and recognize the effects of depression or anxiety on headache to develop specific treatments. PMID- 27270533 TI - Efficacy of Intra-aortic Balloon Pump before versus after Primary Percutaneous Coronary Intervention in Patients with Cardiogenic Shock from ST-elevation Myocardial Infarction. AB - BACKGROUND: Previous studies showed that patients with cardiogenic shock (CS) from ST-elevation acute myocardial infarction (STEMI) supported by intra-aortic balloon pump (IABP) before primary percutaneous coronary intervention (PCI) decreased the risk of in-hospital mortality than patients who received IABP after PCI. However, little evidence is available on the optimal order of IABP insertion and primary PCI. The aim of this study was to investigate the impact of the sequence of IABP support and PCI and its association with major adverse cardiac and cerebrovascular events (MACCEs). METHODS: Data were obtained from 218 consecutive patients with CS due to STEMI in Beijing Anzhen Hospital between 2008 and 2014, who were treated with IABP and PCI. The patients were divided into two groups: Group A in whom IABP received before PCI (n = 106) and Group B in whom IABP received after PCI (n = 112). We evaluated the myocardial perfusion using myocardial blush grade and resolution of ST-segment elevation. The primary endpoint was 12-month risk of MACCE. RESULTS: Most baseline characteristics were similar in patients between the two groups. However, patients received IABP before PCI were associated with a delay of door-to-balloon time (DBT) and higher troponin I level (P < 0.05). However, myocardial perfusion was significantly improved in patients treated with IABP before PCI (P < 0.05). Overall, IABP support before PCI was not associated with significantly lower risk of MACCE (P > 0.05). In addition, risk of all-cause mortality, bleeding, and acute kidney injury (AKI) was similar between two groups (P > 0.05). Multivariate analysis showed that DBT (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.1-4.8, P = 0.04), IABP support after PCI (OR 5.7, 95% CI 2.7-8.4, P = 0.01), and AKI (OR 7.4, 95% CI 4.9-10.8, P = 0.01) were the independent predictors of mortality at 12-month follow-up. CONCLUSIONS: Early IABP insertion before primary PCI is associated with improved myocardial perfusion although DBT increases. IABP support before PCI does not confer a 12-month clinical benefit when used for STEMI with CS. PMID- 27270534 TI - MiR-106b-5p Inhibits Tumor Necrosis Factor-alpha-induced Apoptosis by Targeting Phosphatase and Tensin Homolog Deleted on Chromosome 10 in Vascular Endothelial Cells. AB - BACKGROUND: Apoptosis of endothelial cells (ECs) plays a key role in the development of atherosclerosis and there are also evidence indicated that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a viable target in therapeutic approaches to prevent vascular ECs apoptosis. Aberrant miR-106b-5p expression has been reported in the plasma of patients with unstable atherosclerotic plaques. However, the role and underlying mechanism of miR-106-5p in the genesis of atherosclerosis have not been addressed. In this study, we explored the anti-apoptotic role of miR-106-5p by regulating PTEN expression in vascular ECs. METHODS: Real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the expression levels of miR-106b-5p in human atherosclerotic plaques and normal vascular tissues. Human umbilical vein endothelial cells (HUVEC) were transfected with miR-106b-5p mimic or negative control mimic, and apoptosis was induced by serum starvation and tumor necrosis factor-alpha (TNF-alpha) treat. Western blotting and real-time RT-PCR experiments were used to detect PTEN expression levels and TNF-alpha-induced apoptosis was evaluated by the activation of caspase-3 and cell DNA fragmentation levels in HUVEC. RESULTS: The expression of miR-106b-5p was significantly downregulated in plaques than in normal vascular tissues. TNF-alpha significantly downregulated miR-106b-5p expression levels and upregulated activation of caspase-3 and cell DNA fragmentation levels in HUVEC. Overexpression of miR-106b-5p with miR-106b-5p mimic inhibited PTEN expression and TNF-alpha-induced apoptosis in HUVEC. Luciferase reporter assays confirmed that miR-106b-5p binds to PTEN mRNA 3' untranslated region site. CONCLUSION: MiR-106b-5p could inhibit the expression of PTEN in vascular ECs, which could block TNF-alpha-induced activation of caspase 3, thus prevent ECs apoptosis in atherosclerosis diseases. PMID- 27270535 TI - Association between Carotid Intima-media Thickness and Aldehyde Dehydrogenase 2 Glu504Lys Polymorphism in Chinese Han with Essential Hypertension. AB - BACKGROUND: Aldehyde dehydrogenase 2 (ALDH2) is involved in the pathophysiological processes of cardiovascular diseases. Recent studies showed that mutant ALDH2 could increase oxidative stress and is a susceptible factor for hypertension. In addition, wild-type ALDH2 could improve the endothelial functions, therefore reducing the risk of developing atherosclerosis. The aim of the present study was to explore the frequency of the Glu504Lys polymorphism of the ALDH2 gene and its relation to carotid intima-media thickness (CIMT) in a group of patients with essential hypertension (EH) and to investigate the association between the Glu504Lys polymorphism and CIMT in Chinese Han patients with EH. METHODS: In this study, 410 Chinese Han patients with EH who received physical examinations at the People's Hospital of Sichuan Province (China) were selected. DNA microarray chip was used for the genotyping of the Glu504Lys polymorphism of the ALDH2 gene. The differences in CIMT among patients with different Glu504Lys ALDH2 genotypes were analyzed. RESULTS: The mean CIMT of the patients carrying AA/AG and GG genotypes was 1.02 +/- 0.31 mm and 0.78 +/- 0.28 mm, respectively. One-way ANOVA showed that the CIMT of the patients carrying the AA/AG genotype was significantly higher than in the ones carrying the GG genotype (P < 0.001). Multivariate logistic regression showed that the Glu504Lys AA/AG genotype of the ALDH2 gene was one of the major factors influencing the CIMT in patients with EH (odds ratio = 3.731, 95% confidence interval = 1.589-8.124, P = 0.001). CONCLUSIONS: The Glu504Lys polymorphism of the ALDH2 gene is associated with the CIMT of Chinese Han patients with EH in Sichuan, China. PMID- 27270536 TI - Clinical and Brain Magnetic Resonance Imaging Features in a Cohort of Chinese Patients with Kearns-Sayre Syndrome. AB - BACKGROUND: Kearns-Sayre syndrome (KSS) is a mitochondrial DNA (mtDNA) deletion disorder characterized by a triad of onset before 20 years of age, ophthalmoplegia, and pigmentary retinopathy. The heart and central nervous system are commonly involved. We summarized clinical and brain magnetic resonance imaging (MRI) features of a cohort of Chinese KSS patients. METHODS: Nineteen patients confirmed by muscle biopsy and mtDNA analysis were enrolled. We examined clinical profiles, mainly focusing on changes in electrocardiogram (ECG) and brain MRI. The correlation between genotype and phenotype was statistically analyzed. RESULTS: The mean age of onset was 9.6 +/- 4.3 years, with all developing the classic triad at the time of diagnosis. Heart conduction block was detected in 63.2%, with four initially presenting as bundle branch block and developing into complete atrioventricular block over 3-72 months. Brain MRI showed symmetric high-T2 signals in 100% of cerebral and cerebellar white matter, as well as brainstem, 46.7% of basal ganglia, and 53.3% of thalamus. There were two patterns of cerebral white matter involvements, one with selective subcortical U-fibers and the other with periventricular white matter. The size of mtDNA deletion did not significantly correlate with age of onset or percentage of ragged blue fibers on muscle pathology. CONCLUSIONS: The clinical features of KSS evolve dynamically, affecting the cardiac conduction system predominantly, highlighting the significance of ECG monitoring. Brain MRI showed changes involving both the white matter and deep gray nuclei. Clinical presentation or severity of muscle pathological changes is not related to the size of mtDNA deletions. PMID- 27270537 TI - Skeletal Muscle Magnetic Resonance Imaging of the Lower Limbs in Late-onset Lipid Storage Myopathy with Electron Transfer Flavoprotein Dehydrogenase Gene Mutations. AB - BACKGROUND: Lipid storage myopathy (LSM) is a genetically heterogeneous group with variable clinical phenotypes. Late-onset multiple acyl-coenzyme A dehydrogenation deficiency (MADD) is a rather common form of LSM in China. Diagnosis and clinical management of it remain challenging, especially without robust muscle biopsy result and genetic detection. As the noninvasion and convenience, muscle magnetic resonance imaging (MRI) is a helpful assistant, diagnostic tool for neuromuscular disorders. However, the disease-specific MRI patterns of muscle involved and its diagnostic value in late-onset MADD have not been systematic analyzed. METHODS: We assessed the MRI pattern and fat infiltration degree of the lower limb muscles in 28 late-onset MADD patients, combined with detailed clinical features and gene spectrum. Fat infiltration degree of the thigh muscle was scored while that of gluteus was described as obvious or not. Associated muscular atrophy was defined as obvious muscle bulk reduction. RESULTS: The mean scores were significantly different among the anterior, medial, and posterior thigh muscle groups. The mean of fat infiltration scores on posterior thigh muscle group was significantly higher than either anterior or medial thigh muscle group (P < 0.001). Moreover, the mean score on medial thigh muscle group was significantly higher than that of anterior thigh muscle group (P < 0.01). About half of the patients displayed fat infiltration and atrophy in gluteus muscles. Of 28 patients, 12 exhibited atrophy in medial and/or posterior thigh muscle groups, especially in posterior thigh muscle group. Muscle edema pattern was not found in all the patients. CONCLUSIONS: Late-onset MADD patients show a typical muscular imaging pattern of fat infiltration and atrophy on anterior, posterior, and medial thigh muscle groups, with major involvement of posterior thigh muscle group and gluteus muscles and a sparing involvement of anterior thigh compartment. Our findings also suggest that muscle MRI of lower limbs is a helpful tool in guiding clinical evaluation on late-onset MADD. PMID- 27270538 TI - Evaluation of the Prostate Imaging Reporting and Data System for Magnetic Resonance Imaging Diagnosis of Prostate Cancer in Patients with Prostate-specific Antigen <20 ng/ml. AB - BACKGROUND: The European Society of Urogenital Radiology has built the Prostate Imaging Reporting and Data System (PI-RADS) for standardizing the diagnosis of prostate cancer (PCa). This study evaluated the PI-RADS diagnosis method in patients with prostate-specific antigen (PSA) <20 ng/ml. METHODS: A total of 133 patients with PSA <20 ng/ml were prospectively recruited. T2-weighted (T2WI) and diffusion-weighted (DWI) magnetic resonance images of the prostate were acquired before a 12-core transrectal prostate biopsy. Each patient's peripheral zone was divided into six regions on the images; each region corresponded to two of the 12 biopsy cores. T2WI, DWI, and T2WI + DWI scores were computed according to PI RADS. The diagnostic accuracy of the PI-RADS score was evaluated using histopathology of prostate biopsies as the reference standard. RESULTS: PCa was histologically diagnosed in 169 (21.2%) regions. Increased PI-RADS score correlated positively with increased cancer detection rate. The cancer detection rate for scores 1 to 5 was 2.8%, 15.0%, 34.6%, 52.6%, and 88.9%, respectively, using T2WI and 12.0%, 20.2%, 48.0%, 85.7%, and 93.3%, respectively, using DWI. For T2WI + DWI, the cancer detection rate was 1.5% (score 2), 13.5% (scores 3-4), 41.3% (scores 5-6), 75.9% (scores 7-8), and 92.3% (scores 9-10). The area under the curve for cancer detection was 0.700 (T2WI), 0.735 (DWI) and 0.749 (T2WI + DWI). The sensitivity and specificity were 53.8% and 89.2%, respectively, when using scores 5-6 as the cutoff value for T2WI + DWI. CONCLUSIONS: The PI-RADS score correlates with the PCa detection rate in patients with PSA <20 ng/ml. The summed score of T2WI + DWI has the highest accuracy in detection of PCa. However, the sensitivity should be further improved. PMID- 27270539 TI - Restoration of Brain Acid Soluble Protein 1 Inhibits Proliferation and Migration of Thyroid Cancer Cells. AB - BACKGROUND: Brain acid soluble protein 1 (BASP1) is identified as a novel potential tumor suppressor in several cancers. However, its role in thyroid cancer has not been investigated yet. In the present study, the antitumor activities of BASP1 against the growth and migration of thyroid cancer cells were evaluated. METHODS: BASP1 expression in thyroid cancer tissues and normal tissues were examined by immunohistochemical staining and the association between its expression and prognosis was analyzed. pcDNA-BASP1 carrying full length of BASP1 cDNA was constructed to restore the expression of BASP1 in thyroid cancer cell lines (BHT-101 and KMH-2). The cell proliferation in vitro and in vivo was evaluated by WST-1 assay and xenograft tumor models, respectively. Cell cycle distribution after transfection was analyzed using flow cytometry. Cell apoptosis after transfection was examined by annexin V/propidium iodide assay. The migration was examined using transwell assay. RESULTS: BASP1 expression was abundant in normal tissues while it is significantly decreased in cancer tissues (P = 0.000). pcDNA-BASP1 restored the expression of BASP1 and significantly inhibited the growth of BHT-101 and KMH-2 cells as well as xenograft tumors in nude mice (P = 0.000). pcDNA-BASP1 induced G1 arrest and apoptosis in BHT-101 and KMH-2 cells. In addition, pcDNA-BASP1 significantly inhibited the cell migration. CONCLUSIONS: Downregulation of BASP1 expression may play a role in the tumorigenesis of thyroid cancer. Restoration of BASP1 expression exerted extensive antitumor activities against growth and migration of thyroid cancer cells, which suggested that BASP1 gene might act as a potential therapeutic agent for the treatment of thyroid cancer. PMID- 27270540 TI - A Dosimetric Comparison between Conventional Fractionated and Hypofractionated Image-guided Radiation Therapies for Localized Prostate Cancer. AB - BACKGROUND: Image-guided radiation therapy (IGRT) is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. IGRT using cone-beam computed tomography (CBCT) in combination with volumetric-modulated arc therapy (VMAT) potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dosimetric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy (IMRT) and hypofractionated IGRT using VMAT for patients with localized prostate cancer. METHODS: We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT (n = 12) or VMAT (n = 12) for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography (CT) images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. RESULTS: Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume (PTV) D95% (7663.17 +/- 69.57 cGy vs. 7789.17 +/- 131.76 cGy, P < 0.001). VMAT reduced the rectal D25 (P < 0.001), D35 (P < 0.001), and D50 (P < 0.001), bladder V50 (P < 0.001), D25 (P = 0.002), D35 (P = 0.028), and D50 (P = 0.029). However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT (25.02 +/- 5.54% vs. 27.43 +/- 8.79%, P = 0.087). CONCLUSIONS: To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation delivered to adjacent normal tissues comparing to 7-field, step and-shoot IMRT. Daily online image-guidance and better management of bladder and rectum could make a more precise treatment delivery. PMID- 27270541 TI - Relationship between Intrauterine Bacterial Infection and Early Embryonic Developmental Arrest. AB - BACKGROUND: Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy. The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear. This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest. METHODS: Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion (control group) and from 45 patients who displayed early embryonic developmental arrest (trial group). RESULTS: Intrauterine bacterial infection was discovered in both groups. The infection rate was 24.44% (11/45) in the early embryonic developmental arrest group and 9.09% (3/33) in the artificial abortion group. Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33% (6/45), and none was detected in the artificial abortion group. M. luteus infection was significantly different between the groups (P < 0.05 as shown by Fisher's exact test). In addition, no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest. CONCLUSIONS: M. luteus infection is related to early embryonic developmental arrest and might be one of its causative factors. PMID- 27270543 TI - Corrigendum: Effects of the Combination of Mask Preconditioning with Idazolam Pretreatment on Anxiety and Mask Acceptance during Pediatric Inhalational Induction and Postoperative Mask Fear in Children. PMID- 27270542 TI - Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions. AB - BACKGROUND: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. METHODS: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. RESULTS: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. CONCLUSIONS: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions. PMID- 27270544 TI - Accuracy Assessment of Three-dimensional Surface Reconstructions of In vivo Teeth from Cone-beam Computed Tomography. AB - BACKGROUND: The accuracy of three-dimensional (3D) reconstructions from cone-beam computed tomography (CBCT) has been particularly important in dentistry, which will affect the effectiveness of diagnosis, treatment plan, and outcome in clinical practice. The aims of this study were to assess the linear, volumetric, and geometric accuracy of 3D reconstructions from CBCT and to investigate the influence of voxel size and CBCT system on the reconstructions results. METHODS: Fifty teeth from 18 orthodontic patients were assigned to three groups as NewTom VG 0.15 mm group (NewTom VG; voxel size: 0.15 mm; n = 17), NewTom VG 0.30 mm group (NewTom VG; voxel size: 0.30 mm; n = 16), and VATECH DCTPRO 0.30 mm group (VATECH DCTPRO; voxel size: 0.30 mm; n = 17). The 3D reconstruction models of the teeth were segmented from CBCT data manually using Mimics 18.0 (Materialise Dental, Leuven, Belgium), and the extracted teeth were scanned by 3Shape optical scanner (3Shape A/S, Denmark). Linear and volumetric deviations were separately assessed by comparing the length and volume of the 3D reconstruction model with physical measurement by paired t- test. Geometric deviations were assessed by the root mean square value of the imposed 3D reconstruction and optical models by one sample t-test. To assess the influence of voxel size and CBCT system on 3D reconstruction, analysis of variance (ANOVA) was used (MU = 0.05). RESULTS: The linear, volumetric, and geometric deviations were -0.03 +/- 0.48 mm, -5.4 +/- 2.8%, and 0.117 +/- 0.018 mm for NewTom VG 0.15 mm group; -0.45 +/- 0.42 mm, -4.5 +/- 3.4%, and 0.116 +/- 0.014 mm for NewTom VG 0.30 mm group; and -0.93 +/- 0.40 mm, -4.8 +/- 5.1%, and 0.194 +/- 0.117 mm for VATECH DCTPRO 0.30 mm group, respectively. There were statistically significant differences between groups in terms of linear measurement (P < 0.001), but no significant difference in terms of volumetric measurement (P = 0.774). No statistically significant difference were found on geometric measurement between NewTom VG 0.15 mm and NewTom VG 0.30 mm groups (P = 0.999) while a significant difference was found between VATECH DCTPRO 0.30 mm and NewTom VG 0.30 mm groups (P = 0.006). CONCLUSIONS: The 3D reconstruction from CBCT data can achieve a high linear, volumetric, and geometric accuracy. Increasing voxel resolution from 0.30 to 0.15 mm does not result in increased accuracy of 3D tooth reconstruction while different systems can affect the accuracy. PMID- 27270545 TI - Possible Mechanism of Therapeutic Effect of 3-Methyl-1-phenyl-2-pyrazolin-5-one and Bone Marrow Stromal Cells Combination Treatment in Rat Ischemic Stroke Model. AB - BACKGROUND: The functional improvement following bone marrow stromal cells (BMSCs) transplantation after stroke is directly related to the number of engrafted cells and neurogenesis in the injured brain. Here, we tried to evaluate whether 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), a free radical scavenger, might influence BMSCs migration to ischemic brain, which could promote neurogenesis and thereby enhance treatment effects after stroke. METHODS: Rat transient middle cerebral artery occlusion (MCAO) model was established. Two separate MCAO groups were administered with either MCI-186 or phosphate-buffered saline (PBS) solution to evaluate the expression of stromal cell-derived factor-1 (SDF-1) in ischemic brain, and compared to that in sham group (n = 5/ group/time point[at 1, 3, and 7 days after operation]). The content of chemokine receptor-4 (CXCR4, a main receptor of SDF-1) at 7 days after operation was also observed on cultured BMSCs. Another four MCAO groups were intravenously administered with either PBS, MCI-186, BMSCs (2 * 106), or a combination of MCI-186 and BMSCs (n = 10/group). 5-bromo-2-deoxyuridine (BrdU) and Nestin double-immunofluorescence staining was performed to identify the engrafted BMSCs and neuronal differentiation. Adhesive-removal test and foot-fault evaluation were used to test the neurological outcome. RESULTS: MCI-186 upregulated the expression of SDF 1 in ischemic brain and CXCR4 content in BMSCs was enhanced after hypoxic stimulation. When MCAO rats were treated with either MCI-186, BMSCs, or a combination of MCI-186 and BMSCs, the neurologic function was obviously recovered as compared to PBS control group (P < 0.01 or 0.05, respectively). Combination therapy represented a further restoration, increased the number of BMSCs and Nestin+ cells in ischemic brain as compared with BMSCs monotherapy (P < 0.01). The number of engrafted-BMSCs was correlated with the density of neuronal cells in ischemic brain (r = 0.72 , P < 0.01) and the improvement of foot-fault (r = 0.70, P < 0.01). CONCLUSION: MCI-186 might promote BMSCs migration to the ischemic brain, amplify the neurogenesis, and improve the effects of cell therapy. PMID- 27270546 TI - Sepsis Strengthens Antagonistic Actions of Neostigmine on Rocuronium in a Rat Model of Cecal Ligation and Puncture. AB - BACKGROUND: The antagonistic actions of anticholinesterase drugs on non depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP). METHODS: A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 MUmol/L of neostigmine on Roc (10 MUmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction. RESULTS: Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 MUmol/L; P = 0.009 for 0.5 MUmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 +/- 0.045 vs. 1.047 +/- 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET). CONCLUSIONS: Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ. PMID- 27270548 TI - Novel Insights into the Pathogenesis of Hirschsprung's-associated Enterocolitis. AB - OBJECTIVE: To systematically summary the updated results about the pathogenesis of Hirschsprung's-associated enterocolitis (HAEC). Besides, we discussed the research key and direction based on these results. DATA SOURCES: Our data cited in this review were obtained mainly from PubMed from 1975 to 2015, with keywords "Hirschsprung enterocolitis", "Hirschsprung's enterocolitis", "Hirschsprung's associated enterocolitis", "Hirschsprung-associated enterocolitis", "HAEC", and "EC". STUDY SELECTION: Articles regarding the pathogenesis of HAEC were selected, and the articles mainly regarding the diagnosis, surgical approach, treatment, and follow-up were excluded. RESULTS: Several factors, mainly including mucus barrier, intestinal microbiota, and immune function, as well as some other factors such as genetic variations and surgical reasons, have been found to be related to the pathogenesis of HAEC. Changed quantity and barrier property of mucus, different composition of microbiota, and an abnormal immune state work together or separately trigger HAEC. CONCLUSIONS: The maintenance of intestinal homeostasis is due to a well cooperation of microbiota, mucus barrier, and immune system. If any part presents abnormal, intestinal homeostasis will be broken. Meanwhile, for patients with Hirschsprung's disease or HAEC, dysfunction of these parts has been found. Thus, the happening of HAEC may be mainly attributed to the disorders of intestinal microbiota, mucus barrier, and immune system. PMID- 27270547 TI - Topical Tetracycline Improves MC903-induced Atopic Dermatitis in Mice through Inhibition of Inflammatory Cytokines and Thymic Stromal Lymphopoietin Expression. AB - BACKGROUND: Tetracycline (TET) has been found to have both antibiotic and anti inflammatory properties. The anti-inflammatory effect of topical TET on atopic dermatitis (AD) has not been reported. The purpose of this study was to explore the potential role of topical TET and its anti-inflammatory effects in a mouse model of AD. METHODS: The 2% TET was applied topically to ears of MC903-induced AD-like BALB/c mice once a day. AD-like symptoms and severity were evaluated by assessing skin scoring of dermatitis, ear thickness, and frequency of scratching. Serum IgE and thymic stromal lymphopoietin (TSLP) levels were measured by enzyme linked immunosorbent assay. Western blot was used for analyzing the expressions of TSLP, protease-activated receptor 2 (PAR2), and nuclear factor-kappa B (NF kappaB) in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of TSLP and inflammatory cytokines including interleukin (IL)-4, IL-13, tumor necrosis factor (TNF)-alpha, and IL-1beta in skin lesions. RESULTS: Scoring of dermatitis (9.00 +/- 0.63 vs. 6.67 +/- 1.03, P = 0.001), ear thickness (0.44 +/- 0.02 mm vs. 0.40 +/- 0.03 mm, P = 0.018), and serum IgE level (421.06 +/- 212.13 pg/ml vs. 244.15 +/- 121.39 pg/ml, P = 0.047) were all improved in the 2% TET treatment group compared with AD group. Topical TET significantly reduced the serum level of TSLP (119.04 +/- 38.92 pg/ml vs. 65.95 +/- 54.61 pg/ml, P = 0.011) and both mRNA and protein expressions of TSLP in skin lesions compared with AD group (P = 0.003 and 0.011, respectively), and NF-kappaB and PAR2 expression in skin lesions were also suppressed (P = 0.016 and 0.040, respectively). Furthermore, expressions of inflammatory cytokines IL-4, IL-13, and TNF-alpha in skin lesions were down-regulated in 2% TET group compared with AD group (P = 0.035, 0.008, and 0.044, respectively). CONCLUSIONS: Topical TET exerted anti-inflammatory effects through suppression of TSLP and inflammatory cytokines in AD mouse model, suggesting TET as a potential agent for the topical treatment of AD in the future. PMID- 27270549 TI - Filaggrin Gene Mutation c.3321delA is Associated with Dry Phenotypes of Atopic Dermatitis in the Chinese Han Population. PMID- 27270550 TI - A Case Report on Paraneoplastic Pemphigus Associated Colonic Carcinoma. PMID- 27270552 TI - Pheochromocytoma with Ventricular Tachycardia as the Presenting Symptom. PMID- 27270551 TI - Resolution of Pseudoptosis after Anti-inflammatory Treatment of the Contralateral Eye in Thyroid-associated Ophthalmopathy. PMID- 27270553 TI - AZD9291-induced Acute Interstitial Lung Disease. PMID- 27270554 TI - An Electrode-preserved Patient after Bilateral Intracranial Hematoma Induced by Deep Brain Stimulation. PMID- 27270555 TI - Multiple Intussusceptions in Peutz-Jeghers Syndrome: Detection through Multidetector Computerized Tomography Enterography. PMID- 27270556 TI - NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation. AB - Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood-brain barrier, conventional CD11b(+)CD27(+) NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. By in vivo recruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment, and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation. PMID- 27270557 TI - Overfishing and nutrient pollution interact with temperature to disrupt coral reefs down to microbial scales. AB - Losses of corals worldwide emphasize the need to understand what drives reef decline. Stressors such as overfishing and nutrient pollution may reduce resilience of coral reefs by increasing coral-algal competition and reducing coral recruitment, growth and survivorship. Such effects may themselves develop via several mechanisms, including disruption of coral microbiomes. Here we report the results of a 3-year field experiment simulating overfishing and nutrient pollution. These stressors increase turf and macroalgal cover, destabilizing microbiomes, elevating putative pathogen loads, increasing disease more than twofold and increasing mortality up to eightfold. Above-average temperatures exacerbate these effects, further disrupting microbiomes of unhealthy corals and concentrating 80% of mortality in the warmest seasons. Surprisingly, nutrients also increase bacterial opportunism and mortality in corals bitten by parrotfish, turning normal trophic interactions deadly for corals. Thus, overfishing and nutrient pollution impact reefs down to microbial scales, killing corals by sensitizing them to predation, above-average temperatures and bacterial opportunism. PMID- 27270558 TI - The Prion-Like Properties of Amyloid-beta Assemblies: Implications for Alzheimer's Disease. AB - Since the discovery that prion diseases can be transmitted to experimental animals by inoculation with afflicted brain matter, researchers have speculated that the brains of patients suffering from other neurodegenerative diseases might also harbor causative agents with transmissible properties. Foremost among these disorders is Alzheimer's disease (AD), the most common cause of dementia in the elderly. A growing body of research supports the concept that the pathogenesis of AD is initiated and sustained by the endogenous, seeded misfolding and aggregation of the protein fragment amyloid-beta (Abeta). At the molecular level, this mechanism of nucleated protein self-assembly is virtually identical to that of prions consisting of the prion protein (PrP). The formation, propagation, and spread of Abeta seeds within the brain can thus be considered a fundamental feature of AD pathogenesis. PMID- 27270561 TI - From racemic precursors to fully stereocontrolled products: one-pot synthesis of chiral alpha-amino lactones and lactams. AB - Substituted racemic lactols or cyclic hemiaminals were directly used as nucleophiles in enamine-based asymmetric amination reactions to access enantioenriched alpha-amino lactones or lactams via a one-pot sequence. The desired products, which are very important building blocks in organic synthesis but difficult to be prepared in the optically enriched form, could be afforded with two stereogenic centers in high yields with excellent enantioselectivities. Moreover, starting from the racemic precursors and catalyzed by the enantiomeric pair of the catalyst, all possible stereoisomeric products were discretely provided only after simple column chromatography. Additionally, this protocol provides facile access to several novel bicyclic carbamates, and such drug-like heterocyclic compounds should be potentially useful in medicinal chemistry. PMID- 27270560 TI - Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours. AB - AIMS: Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the extent of intratumoral heterogeneity of Ki67 expression. Our aim was to study the intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with clinicopathological features, such as oestrogen receptor (ER) status, grade and histological subtype. METHODS AND RESULTS: The Ki67-labelling index (Ki67-LI) was assessed in hot, cold and intermediate spots of 233 invasive breast cancers by counting a total of 1020 cells, according to a protocol of the International Ki67 in Breast Cancer Working Group. Differences between the spots per tumour were analysed further for clinicopathological subgroups defined by ER status, grade and histological subtype. All clinicopathological subgroups showed significant differences in Ki67 LI between hot, intermediate and cold spots (P < 0.0001). The coefficient of variance (CV) between the spots was higher in ER-positive than in ER-negative cancers (72.6 versus 49.2%, P < 0.0001), and was highest in grade 3 (96.12%), grade 1 (87.27%) and invasive lobular tumours (83.59%) and lowest in medullary (26.48%) cancers. Nested analysis of variance indicated that in both ER-positive and ER-negative cancers, variance in Ki67-LI within tumours contributed more to the total variance (56% for ER-positive, 60% for ER-negative cancers) than the variance between tumours. CONCLUSION: Intratumoral heterogeneity in Ki67-LI is a ubiquitous phenomenon across various pathological subgroups of breast cancer that may impact assessment of Ki67 levels for clinical decision-making, and sheds new light on recommended cut-offs. PMID- 27270562 TI - Highly fluorescent extended 2-(2'-hydroxyphenyl)benzazole dyes: synthesis, optical properties and first-principle calculations. AB - The investigation of the optical properties of extended 2-(2 hydroxyphenyl)benzazole dyes showed a complete frustration of the excited-state intramolecular proton transfer (ESIPT) process leading to a novel family of highly fluorescent fluorophores. In the case of a benzothiazole ring, restoration of ESIPT can be observed in acidic medium leading to ratiometric sensing. These experimental results have been rationalised by first-principle calculations. PMID- 27270559 TI - Rifamycins, Alone and in Combination. AB - Rifamycins inhibit RNA polymerase of most bacterial genera. Rifampicin remains part of combination therapy for treating tuberculosis (TB), and for treating Gram positive prosthetic joint and valve infections, in which biofilms are prominent. Rifabutin has use for AIDS patients in treating mycobacterial infections TB and Mycobacterium avium complex (MAC), having fewer drug-drug interactions that interfere with AIDS medications. Rifabutin is occasionally used in combination to eradicate Helicobacter pylori (peptic ulcer disease). Rifapentine has yet to fulfill its potential in reducing time of treatment for TB. Rifaximin is a monotherapeutic agent to treat gastrointestinal (GI) disorders, such as hepatic encephalopathy, irritable bowel syndrome, and travelers' diarrhea. Rifaximin is confined to the GI tract because it is not systemically absorbed on oral dosing, achieving high local concentrations, and showing anti-inflammatory properties in addition to its antibacterial activity. Resistance issues are unavoidable with all the rifamycins when the bioburden is high, because of mutations that modify RNA polymerase. PMID- 27270563 TI - Microfluidics 3D gel-island chip for single cell isolation and lineage-dependent drug responses study. AB - 3D cell culture in the extracellular matrix (ECM), which not only provides structural support to cellular constituents, but also initiates regulatory biochemical cues for a variety of important cell functions in tissue, has become more and more important in understanding cancer pathology and drug testing. Although the ECM-gel has been used in cell culture both in bulk and on-chip, previous studies focused on collective cell behavior rather than single-cell heterogeneity. To track the behavior of each individual cell, we have developed a gel-island chip, which can form thousands of islands containing single cells encapsulated by the desired ECM. Optimized by Poisson's distribution, the device can attain 34% single cell capture efficiency of the exact number of single cells per island. A good culture media exchange rate and high cell viability can be achieved in the gel-islands. The cells in the islands can be automatically counted for high-throughput analysis. As a proof of concept, we monitored the proliferation and differentiation of single Notch+ (stem-like) T47D breast cancer cells. The 3D collagen gel environment was found to be favorable for the stem like phenotype through better self-renewal and de-differentiation (Notch- to Notch+ transition). More interestingly, we found that the Notch- de differentiated cells were more resistant to doxorubicin and cisplatin than the Notch+ cells. Combining the 3D ECM culture and single cell resolution, the presented platform can automatically analyze the individual cell behaviors of hundreds of cells using a small amount of drug and reagents. PMID- 27270564 TI - Gene-environment interaction between the MMP9 C-1562T promoter variant and cigarette smoke in the pathogenesis of chronic obstructive pulmonary disease. AB - The aetiology of chronic obstructive pulmonary disease (COPD) is complex. While cigarette smoking is a well-established cause of COPD, a myriad of assessed genetic factors has given conflicting data. Since gene-environment interactions are thought to be implicated in aetiopathogenesis of COPD, we aimed to examine the matrix metalloproteinase (MMP) 9 C-1562T (rs3918242) functional variant and cigarette smoke in the pathogenesis of this disease. The distribution of the MMP9 C-1562T variant was analyzed in COPD patients and controls with normal pulmonary function from Serbia. Interaction between the C-1562T genetic variant and cigarette smoking was assessed using a case-control model. The response of the C 1562T promoter variant to cigarette smoke condensate (CSC) exposure was examined using a dual luciferase reporter assay. The frequency of T allele carriers was higher in the COPD group than in smoker controls (38.4% vs. 20%; OR = 2.7, P = 0.027). Interaction between the T allele and cigarette smoking was identified in COPD occurrence (OR = 4.38, P = 0.005) and severity (P = 0.001). A functional analysis of the C-1562T variant demonstrated a dose-dependent and allele-specific response (P < 0.01) to CSC. Significantly higher MMP9 promoter activity following CSC exposure was found for the promoter harboring the T allele compared to the promoter harboring the C allele (P < 0.05). Our study is the first to reveal an interaction between the MMP9-1562T allele and cigarette smoke in COPD, emphasising gene-environment interactions as a possible cause of lung damage in the pathogenesis of COPD. Environ. Mol. Mutagen. 57:447-454, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27270565 TI - Evaluation of cutaneous surface parameters in psoriatic patients. AB - PURPOSE: The purpose of this study was to compare cutaneous surface parameters in lesional and non-lesional skin of psoriatic patients and in corresponding areas of control subjects. METHODS: Sixty-six psoriatic patients (of any grade of severity, with or without arthritis, without any therapy other than systemic biologic drugs) and 28 healthy controls were enrolled in this observational, case control study. Exclusion criteria were current or past sebo-psoriasis and seborrheic dermatitis, pustular or erithrodermic psoriasis; treatment with immune suppressive agents, retinoids, or ultraviolet phototherapy in the last 6 months; topical treatment in the last 2 weeks. Corneometry, sebumetry, and pHmetry were evaluated on non-lesional skin of forehead, cheek, chin and volar region of forearm, and on a psoriatic plaque (on elbow or neighboring areas); in controls, the same areas were considered. RESULTS: Corneometry values were significantly lower in psoriatic plaques vs. elbows of controls. Sebumetry showed significantly higher values in non-lesional forearm skin and plaques of psoriatic patients vs. corresponding areas of controls. pH was significantly lower in all areas in psoriasis. No differences were found between patients treated or not with biologics and with or without arthritis. CONCLUSION: Evaluating surface skin parameters in psoriasis is useful to better understand the etiopathogenic mechanism and could suggest new therapeutic approaches. PMID- 27270567 TI - Injectable shear-thinning nanoengineered hydrogels for stem cell delivery. AB - Injectable hydrogels are investigated for cell encapsulation and delivery as they can shield cells from high shear forces. One of the approaches to obtain injectable hydrogels is to reinforce polymeric networks with high aspect ratio nanoparticles such as two-dimensional (2D) nanomaterials. 2D nanomaterials are an emerging class of ultrathin materials with a high degree of anisotropy and they strongly interact with polymers resulting in the formation of shear-thinning hydrogels. Here, we present 2D nanosilicate reinforced kappa-carrageenan (kappaCA) hydrogels for cellular delivery. kappaCA is a natural polysaccharide that resembles native glycosaminoglycans and can form brittle hydrogels via ionic crosslinking. The chemical modification of kappaCA with photocrosslinkable methacrylate groups renders the formation of a covalently crosslinked network (MkappaCA). Reinforcing the MkappaCA with 2D nanosilicates results in shear thinning characteristics, and enhanced mechanical stiffness, elastomeric properties, and physiological stability. The shear-thinning characteristics of nanocomposite hydrogels are investigated for human mesenchymal stem cell (hMSC) delivery. The hMSCs showed high cell viability after injection and encapsulated cells showed a circular morphology. The proposed shear-thinning nanoengineered hydrogels can be used for cell delivery for cartilage tissue regeneration and 3D bioprinting. PMID- 27270568 TI - Hydration and Thermal Expansion in Anatase Nanoparticles. AB - A tunable thermal expansion is reported in nanosized anatase by taking advantage of surface hydration. The coefficient of thermal expansion of 4 nm TiO2 along a axis is negative with a hydrated surface and is positive without a hydrated surface. High-energy synchrotron X-ray pair distribution function analysis combined with ab initio calculations on the specific hydrated surface are carried out to reveal the local structure distortion that is responsible for the unusual negative thermal expansion. PMID- 27270566 TI - The diameter response of retinal arterioles in diabetic maculopathy is reduced during hypoxia and is unaffected by the inhibition of cyclo-oxygenase and nitric oxide synthesis. AB - PURPOSE: Diabetic retinopathy is accompanied with changes in the diameter regulation and oxygenation of retinal vessels. Previous studies have shown that in normal persons and in diabetic patients without retinopathy hypoxia-induced vasodilatation is mediated by cyclo-oxygenase (COX) products and nitric oxide (NO). The purpose of the present study was to study whether these effects can be reproduced in patients with diabetic maculopathy. METHODS: Eighteen patients with diabetic maculopathy aged 29-57 years were examined using the Dynamic Vessel Analyzer. The resting diameter and the diameter changes of retinal arterioles during isometric exercise and flicker stimulation were studied before and during breathing a hypoxic gas mixture. The examinations were also performed before and during intravenous infusion of the NOS inhibitor L-NMMA, and were repeated on a second day after topical administration of the COX-inhibitor diclofenac. RESULTS: The diameter of retinal arterioles showed no significant change during hypoxia or L-NMMA infusion, or after topical application of diclofenac (p > 0.25 for all comparisons). The resting diameter of the venules was significantly increased during hypoxia (p = 0.003) and decreased during L-NMMA infusion (p < 0.0001). The diameter of retinal venules during isometric exercise increased significantly during hypoxia (p = 0.01). Flicker stimulation induced significant dilatation of the venules, which was significantly reduced during hypoxia and increased during L-NMMA infusion (p < 0.0001 for all comparisons). CONCLUSION: Hypoxia-induced dilatation of retinal arterioles is severely reduced in patients with diabetic maculopathy. Future intervention studies aimed at normalizing the diameter regulation of retinal arterioles in diabetic patients should preferentially be conducted in the early stages of the disease where the potential for changing the vessel diameter is preserved. ClinicalTrials.gov identifier: NCT01689090. PMID- 27270569 TI - 2D layered transport properties from topological insulator Bi2Se3 single crystals and micro flakes. AB - Low-field magnetotransport measurements of topological insulators such as Bi2Se3 are important for revealing the nature of topological surface states by quantum corrections to the conductivity, such as weak-antilocalization. Recently, a rich variety of high-field magnetotransport properties in the regime of high electron densities (~10(19) cm(-3)) were reported, which can be related to additional two dimensional layered conductivity, hampering the identification of the topological surface states. Here, we report that quantum corrections to the electronic conduction are dominated by the surface states for a semiconducting case, which can be analyzed by the Hikami-Larkin-Nagaoka model for two coupled surfaces in the case of strong spin-orbit interaction. However, in the metallic-like case this analysis fails and additional two-dimensional contributions need to be accounted for. Shubnikov-de Haas oscillations and quantized Hall resistance prove as strong indications for the two-dimensional layered metallic behavior. Temperature-dependent magnetotransport properties of high-quality Bi2Se3 single crystalline exfoliated macro and micro flakes are combined with high resolution transmission electron microscopy and energy-dispersive x-ray spectroscopy, confirming the structure and stoichiometry. Angle-resolved photoemission spectroscopy proves a single-Dirac-cone surface state and a well-defined bulk band gap in topological insulating state. Spatially resolved core-level photoelectron microscopy demonstrates the surface stability. PMID- 27270570 TI - Quantitative Real-Time PCR and Platelia Galactomannan Assay for the Diagnosis of Invasive Pulmonary Aspergillosis: Bronchoalveolar Lavage Fluid Performs Better Than Serum in Non-neutropaenic Patients. AB - The diagnosis of invasive pulmonary aspergillosis (IPA) is still in challenge in clinical practice, particularly for those patients without an obvious neutropaenia. In this study, a well-validated qPCR method and Platelia galactomannan (GM) assay were compared for their diagnostic performance using paired samples of bronchoalveolar lavage (BAL) fluid and serum from predominantly non-neutropaenic patients. In the serum samples, qPCR showed a comparable performance with GM assay in terms of sensitivity and specificity. In the BAL samples, qPCR and GM assay both demonstrated a good sensitivity (90 vs. 90 %); however, the specificity of qPCR was higher than that of GM assay (92.5 vs. 68.8 %, P < 0.001) in these samples. A better sensitivity was obtained with BAL compared with serum samples for both GM assay (90 vs. 50 %) and qPCR (90 vs. 60 %). In conclusion, in non-neutropaenic patients, BAL appears to provide improved sensitivity for both GM and qPCR assays. BAL qPCR offers a better diagnostic value for IPA compared with BAL GM assay, significantly increasing the specificity without affecting the sensitivity. PMID- 27270572 TI - Characterisation of non-coding genetic variation in histamine receptors using AnNCR-SNP. AB - Almost 90 % of disease-associated genetic variants found using genome wide association studies (GWAS) are located in non-coding regions of the genome. Such variants can affect phenotype by altering important regulatory elements such as promoters, enhancers or repressors, leading to changes in gene expression and consequently disease, such as thyroid cancer and allergic diseases. A number of allergy and atopy related diseases such as asthma and atopic dermatitis are related to histamine receptors; however, these diseases are not fully characterized at the molecular level. Moreover, candidate gene based studies of common variants known as single nucleotide polymorphism (SNPs) located in the coding regions of these receptors have given mixed results. It is important to complement these approaches by identifying and characterising non-coding variants in order to further elucidate the role of these receptors in disease. Here we present an analysis of histamine receptor genes using the tool AnNCR-SNP to characterise variants in non-coding genomic regions. AnNCR-SNP combines bioinformatics and experimental data sets from various sources to predict the effects of genetic variation on gene expression regulation. We find many SNPs located in areas of open chromatin, overlapping with transcription factor binding sites and associated with changes in gene expression in expression quantitative trait loci (eQTL) experiments. Here we present the results as a catalogue of non coding variation in histamine receptor genes to aid histamine researchers in identifying putative functional SNPs found in GWAS for further validation, and to help select variants for candidate gene studies. PMID- 27270571 TI - In vitro and in vivo evaluation of BMAP-derived peptides for the treatment of cystic fibrosis-related pulmonary infections. AB - Patients with cystic fibrosis require pharmacological treatment against chronic lung infections. The alpha-helical antimicrobial peptides BMAP-27 and BMAP-28 have shown to be highly active in vitro against planktonic and sessile forms of multidrug-resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Stenotrophomonas maltophilia cystic fibrosis strains. To develop small antibacterial peptides for therapeutic use, we tested shortened/modified BMAP fragments, and selected the one with the highest in vitro antibacterial activity and lowest in vivo acute pulmonary toxicity. All the new peptides have shown to roughly maintain their antibacterial activity in vitro. The 1-18 N-terminal fragment of BMAP-27, showing MIC90 of 16 ug/ml against P. aeruginosa isolates and strain-dependent anti-biofilm effects, showed the lowest pulmonary toxicity in mice. However, when tested in a murine model of acute lung infection by P. aeruginosa, BMAP-27(1-18) did not show any curative effect. If exposed to murine broncho-alveolar lavage fluid BMAP-27(1-18) was degraded within 10 min, suggesting it is not stable in pulmonary environment, probably due to murine proteases. Our results indicate that shortened BMAP peptides could represent a starting point for antibacterial drugs, but they also indicate that they need a further optimization for effective in vivo use. PMID- 27270573 TI - Role of tissue transglutaminase-2 (TG2)-mediated aminylation in biological processes. AB - Post-translational modification (PTM) is an important mechanism in modulating a protein's structure and can lead to substantial diversity in biological function. Compared to other forms of PTMs such as phosphorylation, acetylation and glycosylation, the physiological significance of aminylation is limited. Aminylation refers to the covalent incorporation of biogenic/polyamines into target protein by calcium-dependent transglutaminases (TGs). The development of novel and more sensitive techniques has led to more proteins identified as tissue transglutaminase (TG2) substrates and potential targets for aminylation. Many of these substrate proteins play a role in cell signaling, cytoskeleton organization, muscle contraction, and inflammation. TG2 is well studied and widely expressed in a variety of tissues and will be the primary focus of this review on recent advance in transglutaminase-mediated aminylation. PMID- 27270574 TI - Physical Control of Spider Mites Using Ultraviolet-B With Light Reflection Sheets in Greenhouse Strawberries. AB - Development of spider mite management technology other than chemical control is desired because of the serious development of acaricide resistance worldwide. Recent studies have evidenced the lethal effects of ultraviolet-B (UVB) radiation on spider mites. To develop the technology on how to use UVB irradiation for spider mite control, we tested whether UVB lamp-light reflection sheet (LRS) combinations suppressed the population size of Tetranychus urticae Koch on strawberry in a greenhouse from December to May (2012-2013, 2013-2014) in Japan. We designed four combinations of UVB lamps and LRSs: 1) neither UVB lamps nor LRSs (UV-LRS-); 2) a UVB lamp without an LRS (UV+LRS-; 2012-2013 only); 3) a UVB lamp and a mulch-type LRS (UV+LRSm); and 4) a UVB lamp and a wing-type LRS (UV+LRSw). The number of adult females peaked at 438.0 and 222.0 per plant in UV LRS- of 2012-2013 and 2013-2014, respectively, and peaked at 191.6 females in UV+LRS- of 2012-2013. In contrast, the peak abundance was 20.9-98.0 females in UV+LRSm, and fewer than 15 females were noted in UV+LRSw over either experimental period. UVB irradiance on lower leaf surfaces was higher in UV+LRSm and UV+LRSw than UV-LRS- and UV+LRS-, and the mite densities were significantly correlated with UVB irradiance on lower leaf surfaces. Consequently, we conclude that the combinations of UVB lamp-LRS have an excellent capacity to control T. urticae on greenhouse strawberry, and that the LRS was an essential component in this technological approach. PMID- 27270575 TI - Effects of Periodically Repeated Heat Events on Reproduction and Ovary Development of Agasicles hygrophila (Coleoptera: Chrysomelidae). AB - Insect development occurs within a specific temperature range. Constant temperature studies may produce misleading information on the eco-physiological impacts of temperature on the population dynamics of an insect species, as in most natural environments, temperature usually undergoes daily variation. In China, field surveys showed that the decline in the Agasicles hygrophila (Selman & Vogt) (Coleoptera: Chrysomelidae) population from early August to late September in summer resulted in difficulties in effectively controlling the population of Alternanthera philoxeroides (Mart.) Griseb (Amaranthaceae). Previous studies have largely ignored more natural, fluctuating conditions. In our study, we first investigated the impacts of different temperature conditions (25 degrees C constant temperature for 20 h with a 4-h period of a high temperature of either 30 degrees C, 33 degrees C, 36 degrees C, or 39 degrees C) on adult reproduction and longevity, egg development time, egg hatch rate, female ovarian development, and oogenesis of A. hygrophila. Our results indicated that high temperatures of 30 degrees C and 33 degrees C did not affect the female ovarian development and oogenesis of A. hygrophila Contrarily, high temperatures of 36 degrees C and 39 degrees C negatively affected the population development of A. hygrophila. At 36 degrees C and 39 degrees C, the egg hatch rates were very low, and the egg development times significantly lengthened. The frequency of abnormal ovaries significantly rose at 39 degrees C. We concluded that the decline in the A. hygrophila population during August and September may be related to the extreme high temperatures that frequently occur in summer. These results help provide a better understanding of A. hygrophila population dynamics under natural conditions. PMID- 27270576 TI - Contact Toxicity of Deltamethrin Against Tribolium castaneum (Coleoptera: Tenebrionidae), Sitophilus oryzae (Coleoptera: Curculionidae), and Rhyzopertha dominica (Coleoptera: Bostrichidae) Adults. AB - This study was conducted at Oklahoma State University, Stillwater, OK, to evaluate the response to deltamethrin concentrations for adults of three stored product insects, Tribolium castaneum (Herbst), Sitophilus oryzae (L.), and Rhyzopertha dominica (F.). In insect toxicological studies, knockdown is the state of intoxication and partial paralysis as a result of exposure to an insecticide. Deltamethrin concentrations ranging from 0.48 to 140 mg/m(2) (1 to 3,000 ppm) were sprayed on glass Petri dishes. After the dishes dried, 20 adult insects of each species were placed on the treated dishes to determine the contact toxicity of deltamethrin. Assessments for knockdown were made at 15-min intervals for up to 8 h after initial exposure and then again after 24 or 48 h. Insects were then transferred to clean untreated Petri dishes with diet and observed from 0.5 to 72 h. Mortality was assessed 72 h after transfer to untreated dishes with food material. Deltamethrin was highly effective against all three species tested and achieved 99% knockdown of insects of all species within 4 h after exposure at concentrations >=1.2 mg/m(2) Although some insects recovered from initial knockdown at concentrations <=48 mg/m(2), nearly all the insects were killed at 140 mg/m(2) when exposed for 48 h. LC95 values for all species tested, for the 48-h exposure period, were <140 mg/m(2), the concentration of deltamethrin that could potentially be present in new ZeroFly Storage Bag fabric. ZeroFly bags are used for stored-product insect pest control. PMID- 27270577 TI - Diagnosis of Lobesia botrana (Lepidoptera: Tortricidae) Using Real-Time PCR. AB - A real-time PCR assay is reported for identification of Lobesia botrana (Denis and Schiffermuller) collected in California. This assay multiplexes two independent TaqMan probe systems in a single reaction tube to reduce handling time and sample exposure to environmental contaminants. One probe system targets a segment of DNA located in the internal transcribed spacer region 2 (ITS2) that is present in the L. botrana genome but absent in native North American Tortricidae. The second probe system serves as a control for DNA quality by targeting a segment of the 18S rDNA gene that is conserved in L. botrana and all of the tested nontarget species. The assay successfully diagnosed 70 Lobesia botrana specimens and 95 nontarget specimens. No false-positive or false-negative results were observed supporting its application for identification of this pest in California. PMID- 27270578 TI - Effectiveness of vesicoamniotic shunt in fetuses with congenital lower urinary tract obstruction: an updated systematic review and meta-analysis. AB - OBJECTIVE: To evaluate the effect on perinatal and postnatal survival of vesicoamniotic shunt (VAS) as treatment for fetal lower urinary tract obstruction (LUTO). METHODS: An electronic search of Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews and Scopus using relevant search terms was conducted from inception to June 2015 to identify studies comparing outcomes of VAS vs conservative management for treatment of LUTO. Cohort studies and clinical trials were considered eligible. Single-arm studies and studies that did not report survival were excluded. Sample size and language were not criteria for exclusion. Two reviewers extracted independently data in a standardized form, including study characteristics and results. Primary outcomes were perinatal and postnatal survival. Secondary outcome was postnatal renal function. Data on fetal survival were expressed as odds ratio (OR) and 95% CI. RESULTS: Of the 423 abstracts retrieved, nine studies were eligible for inclusion. These studies included 112 fetuses treated with VAS and 134 that were managed conservatively. There was heterogeneity in study design. Although the data demonstrated a difference in effect estimates between the study arms in terms of perinatal survival (OR, 2.54 (95% CI, 1.14-5.67)), there was no difference in 6-12-month survival (OR, 1.77 (95% CI, 0.25-12.71)) or 2-year survival (OR, 1.81 (95% CI, 0.09-38.03)). In addition, there was no difference in effect on postnatal renal function between fetuses that underwent intervention and those that did not (OR, 2.09 (95% CI, 0.74-5.94)). CONCLUSIONS: Available data seem to support an advantage for perinatal survival in fetuses treated with VAS compared with conservative management. However, 1-2-year survival and outcome of renal function after VAS procedure remain uncertain. Further studies are necessary to evaluate the effectiveness of fetal intervention for LUTO based on different severity of the disease, due to the very low quality of the studies according to GRADE guidelines. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27270579 TI - Increased telocytes involved in the proliferation of vascular smooth muscle cells in rat carotid artery balloon injury. AB - Telocytes (TCs) are a novel type of interstitial cells that are thought to be involved in tissue regeneration and repair. However, the possible roles of TCs in vascular diseases remain unclear. In this study, we used a rat model of carotid artery balloon injury (CABI) to study the changes and potential roles of vascular TCs after vascular injury. Transmission electron microscopy (TEM) and CD34/vimentin immunolabeling were used to identify and quantify TCs in normal and injured carotid arteries. Quantitative immunofluorescence analysis revealed that, compared with the sham group, the number of TCs in the CABI group increased from 7.2+/-1.0 to an average of 20.4+/-1.8 per 1-mm(2) vascular area. The expression level of miR-24 in TCs was three times higher than in vascular smooth muscle cells (VSMCs). The percentage of VSMCs in S phase and G2/M phase increased by approximately 5% when VSMCs were incubated with the supernatant of TCs. The antagomir of miR-24 in TCs reduced the ratio of VSMCs in S phase and G2/M phase. This study illuminates the function of TCs in the proliferation of VSMCs. PMID- 27270580 TI - Screening and identification of human ZnT8-specific single-chain variable fragment (scFv) from type 1 diabetes phage display library. AB - Zinc transporter 8 (ZnT8) is a major autoantigen and a predictive marker in type 1 diabetes (T1D). To investigate ZnT8-specific antibodies, a phage display library from T1D was constructed and single-chain antibodies against ZnT8 were screened and identified. Human T1D single-chain variable fragment (scFv) phage display library consists of approximately 1*10(8) clones. After four rounds of bio-panning, seven unique clones were positive by phage ELISA. Among them, C27 and C22, which demonstrated the highest affinity to ZnT8, were expressed in Escherichia coli Top10F' and then purified by affinity chromatography. C27 and C22 specifically bound ZnT8 N/C fusion protein and ZnT8 C terminal dimer with one Arg325Trp mutation. The specificity to human islet cells of these scFvs were further confirmed by immunohistochemistry. In conclusion, we have successfully constructed a T1D phage display antibody library and identified two ZnT8-specific scFv clones, C27 and C22. These ZnT8-specific scFvs are potential agents in immunodiagnostic and immunotherapy of T1D. PMID- 27270581 TI - Current status of the implantable LVAD. AB - With the ongoing shortage of available organs for heart transplantation, mechanical circulatory support devices have been increasingly utilized for managing acute and chronic heart failure that is refractory to medical therapy. In particular, the introduction of the left ventricular assist devices (LVAD) has revolutionized the field. In this review, we will discuss a brief history of the LVAD, available devices, current indications, patient selection, complications, and outcomes. In addition, we will discuss recent outcomes and advancements in the field of noncardiac surgery in the LVAD patient. Finally, we will discuss several topics for surgical consideration during LVAD implantation. PMID- 27270582 TI - Perceived learning needs according to patients who have undergone major coronary interventions and their nurses. AB - AIMS AND OBJECTIVES: The aim of this study was to identify the differences in perceived learning needs between cardiac patients who have undergone major coronary interventions and their nurses. BACKGROUND: The decrease in length of stay after cardiac interventions has signalled an urgent need to provide effective in-hospital health education. Therefore, the content of health education should bridge the gap between nurses' and patients' views of what information is important for ensuring patients' optimum recovery. DESIGN: A descriptive comparative design was employed. METHODS: Patients were invited to participate if they had undergone angioplasty or bypass surgery and were ready for discharge within 24-48 hours. A convenience sample of 365 cardiac patients and 166 cardiac nurses participated in this study. Baseline data on patients' and nurses' sociodemographics, clinical history and experience were collected through personal interviews. Then, participants completed the Patient Learning Needs Scale to identify their perceptions of the learning needs after cardiac interventions. RESULTS: The top-priority learning needs according to both patients and cardiac nurses was information on wound care and medication. In contrast, the lowest-priority learning need was physical activity. Nurses perceived information about physical activity as most needed to patients, whereas patients perceived information about medications, postintervention complications and postintervention concerns as mostly needed. CONCLUSION: The disparity between perceptions of patient and nurses on the essential content to be learned highlights the importance of considering both of these parties when establishing health education programmes. In addition, nurses should focus more on information related to the recovery period and immediate needs after discharge. RELEVANCE TO CLINICAL PRACTICE: Information about wound care, medication and potential complications should be the core of predischarge education programmes. In addition, nurses should focus on improve patients' awareness of secondary prevention and lifestyle modification, as patients pay less attention to these vital topics. PMID- 27270583 TI - [Primary cutaneous cribriform apocrine carcinoma : An underdiagnosed entity?]. AB - Primary cutaneous cribriform apocrine carcinoma is a distinctive but little known variant of cutaneous apocrine carcinoma with indolent biological behaviour. It should not be mistaken for a cutaneous metastasis of a visceral carcinoma, an adenoid cystic basal cell carcinoma or a primary cutaneous adenoid cystic carcinoma. PMID- 27270585 TI - A retrospective comparison of helicopter transport versus ground transport in patients with severe sepsis and septic shock. AB - BACKGROUND: Helicopter emergency medical services (HEMS) extend the reach of a tertiary care center significantly. However, its role in septic patients is unclear. Our study was performed to clarify the role of HEMS in severe sepsis and septic shock. METHODS: This is a single-center retrospective cohort study. This study was performed at Mayo Clinic, Rochester, MN, in years 2007-2009. This study included a total of 181 consecutive adult patients admitted to the medical intensive care unit meeting criteria for severe sepsis or septic shock within 24 h of admission and transported from an acute care facility by a helicopter or ground ambulance. The primary predictive variable was the mode of transport. Multiple demographic, clinical, and treatment variables were collected and analyzed with univariate analysis followed by multivariate analysis. RESULTS: The patients transported by HEMS had a significantly faster median transport time (1.3 versus 1.7 h, p < 0.01), faster time to meeting criteria for severe sepsis or septic shock (1.2 versus 2.9 h, p < 0.01), a higher SOFA score (9 versus 7, p < 0.01), higher incidence of acute respiratory distress syndrome (38 versus 18 %, p = 0.013), higher need for invasive mechanical ventilation (60 versus 41 % p = 0.014), higher ICU mortality (13.3 versus 4.1 %, p = 0.024), and an increased hospital mortality (17 versus 30 %, p = 0.04) when compared to those transported by ground. Distance traveled was not an independent predictor of hospital mortality on multivariate analysis. CONCLUSIONS: HEMS transport is associated with faster transport time, carries sicker patients, and is associated with higher hospital mortality compared with ground ambulance services for patients with severe sepsis or septic shock. PMID- 27270584 TI - HDAC inhibition promotes both initial consolidation and reconsolidation of spatial memory in mice. AB - Accumulating evidence suggests a critical role for epigenetic regulations in long term memory (LTM) formation. Among them, post-translational modifications of proteins, as histone acetylation, are an important regulator of chromatin remodelling and gene transcription. While the implication of histone acetylation in memory consolidation is widely accepted, less is known about its role in memory reconsolidation i.e. during memory restabilization after its reactivation. In the present study, we investigated the role of histone acetylation during the initial consolidation and the reconsolidation of spatial memory, using a weak massed learning procedure in the Morris water maze paradigm in mice. Usually a weak learning is sufficient for short term memory (STM) formation, but insufficient to upgrade STM to LTM. We found that promoting histone acetylation through intra-hippocampal infusion of a class I selective histone deacetylase (HDAC) inhibitor immediately after a subthreshold spatial learning improved LTM but not STM retention. More importantly, inhibiting HDAC activity after the reactivation of a weak memory promoted specifically LTM reconsolidation without affecting post-reactivation STM. These findings argue in favour of an important role for histone acetylation in memory consolidation, and more particularly during the reconsolidation of spatial memory in mice. PMID- 27270586 TI - Chemotherapy-Induced Neurotoxicity: Evidence of a Protective Role of CC Homozygosis in the Interleukin-1beta Gene-511 C>T Polymorphism. AB - We hypothesized that the IL-1beta-511 C>T polymorphism could be associated with the development of neurotoxicity and that it could be a possible biomarker to rate the risk of occurrence of neurotoxicity in cancer patients. Genomic DNA was extracted from 85 cancer patients: 49 received systemic chemotherapeutic treatment (CHT) and 36 patients did not receive it (No-CHT). All subjects were genotyped for the functionally active polymorphisms of IL-1beta-511 C>T. We estimated neurotoxicity with the evaluation of neurological deficits. CHT patients showed erythrocytopenia, neurological deficit and a slight lowering of cognitive performance. The subgroup of patients carrying the CC genotype of the IL-1beta-511 C>T gene showed lesser neurological deficits. In the context of cancer treatment, we suggested the potential value of IL-1beta-511 C>T as genetic biomarkers to identify patients with higher risk to develop neurological deficits. PMID- 27270590 TI - Structure of cobalt protoporphyrin chloride and its dimer, observation and DFT modeling. AB - In this article we present a joint study by time-of-flight mass spectroscopy and density functional theory of cobalt protoporphyrin dimer complexes. The main novelty of the experimental part is to reveal the formation of porphyrin dimers that eventually include a chlorine atom. Density functional theory calculations have been performed to shed light on the structural and electronic properties of monomers and dimers that may be formed experimentally. Various geometries of the monomers are analyzed in the two lowest spin states. The electronic structures are examined by means of population analysis relying on the iterative Hirshfeld scheme and the topological analyses of the electron localization function. It is shown that the cobalt ligand bond is purely ionic in the triplet states but shows a noticeable covalent character in the singlet state. Ionization potential of Co protoporphyrin and binding energies of the chlorine ligand are also reported. Concerning the dimers, several association patterns are investigated for the chlorinated and non-chlorinated complexes. It is found that the structures of the most stable complexes involve four hydrogen bonds between the carboxylic acid moieties of the protoporphyrins. However other association modes are likely to be possible in the experiments. PMID- 27270587 TI - Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness. AB - The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst; also known as rhodanese) as a candidate obesity resistance gene with selectively increased expression in adipocytes. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Tst-deficient mice showed markedly exacerbated diabetes, whereas pharmacological activation of TST ameliorated diabetes in mice. Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, TST mRNA expression in adipose tissue correlated positively with insulin sensitivity in adipose tissue and negatively with fat mass. Thus, the genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for individuals with type 2 diabetes. PMID- 27270591 TI - Changes in biological productivity associated with Ningaloo Nino/Nina events in the southern subtropical Indian Oceanin recent decades. AB - Using observations and long term simulations of an ocean-biogeochemical coupled model, we investigate the biological response in the southern subtropical Indian Ocean (SIO) associated with Ningaloo Nino and Nina events. Ningaloo events have large impact on sea surface temperature (SST) with positive SST anomalies (SSTA) seen off the west coast of Australia in southern SIO during Ningaloo Nino and negative anomalies during Nina events. Our results indicate that during the developing period of Ningaloo Nino, low chlorophyll anomaly appears near the southwest Australian coast concurrently with high SSTA and vice-versa during Nina, which alter the seasonal cycle of biological productivity. The difference in the spatiotemporal response of chlorophyll is due to the southward advection of Leeuwin current during these events. Increased frequency of Ningaloo Nino events associated with cold phase of Pacific Decadal Oscillation (PDO) resulted in anomalous decrease in productivity during Austral summer in the SIO in the recent decades. PMID- 27270588 TI - Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. AB - Brain metastases represent the greatest clinical challenge in treating HER2 positive breast cancer. We report the development of orthotopic patient-derived xenografts (PDXs) of HER2-expressing breast cancer brain metastases (BCBM), and their use for the identification of targeted combination therapies. Combined inhibition of PI3K and mTOR resulted in durable tumor regressions in three of five PDXs, and therapeutic response was correlated with a reduction in the phosphorylation of 4EBP1, an mTORC1 effector. The two nonresponding PDXs showed hypermutated genomes with enrichment of mutations in DNA-repair genes, which suggests an association of genomic instability with therapeutic resistance. These findings suggest that a biomarker-driven clinical trial of PI3K inhibitor in combination with an mTOR inhibitor should be conducted for patients with HER2 positive BCBM. PMID- 27270592 TI - Nimbolide Inhibits Nuclear Factor-KB Pathway in Intestinal Epithelial Cells and Macrophages and Alleviates Experimental Colitis in Mice. AB - Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The effect of nimbolide on the nuclear factor-kappa B (NF-kappaB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models was investigated. The IEC COLO 205, the murine macrophage cell line RAW 264.7, and peritoneal macrophages from interleukin-10-deficient (IL 10-/- ) mice were preconditioned with nimbolide and then stimulated with tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide. Dextran sulfate sodium induced acute colitis model and chronic colitis model in IL-10-/- mice were used for in vivo experiments. Nimbolide significantly suppressed the expression of inflammatory cytokines (IL-6, IL-8, IL-12, and TNF-alpha) and inhibited the phosphorylation of IkappaBalpha and the DNA-binding affinity of NF-kappaB in IECs and macrophages. Nimbolide ameliorated weight loss, colon shortening, disease activity index score, and histologic scores in dextran sulfate sodium colitis. It also improved histopathologic scores in the chronic colitis of IL-10-/- mice. Staining for phosphorylated IkappaBalpha was significantly decreased in the colon tissue after treatment with nimbolide in both models. Nimbolide inhibits NF kappaB signaling in IECs and macrophages and ameliorates experimental colitis in mice. These results suggest nimbolide could be a potentially new treatment for inflammatory bowel disease. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270593 TI - Project 6 Summit: SAGES telementoring initiative. AB - BACKGROUND: Advances in telecommunications technology have facilitated telementoring initiatives that virtually link a mentor and mentee in the operating room and have shown significant promise in conferring high rates of safe procedure adoption. Recognizing that telementoring has the potential to be one solution to the global demand for what is sure to be a constant need for surgical retraining and safe incorporation of new technologies, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) convened the Project 6 Summit. METHODS: Content experts in minimally invasive surgery, surgical mentoring and telementoring, surgical education, business development, healthcare innovation, and regulation were invited to attend a two-day summit to outline the current state of surgical telementoring and chart the challenges and opportunities going forward. RESULTS: Five opportunity buckets consisting of: Legal and Regulatory, Business Development and Proving Value, Effective Communication and Education Requirements, Technology Requirements and Logistics were the subject of focused working groups and subsequent review and consensus by summit attendees. The current state-of-the-art and guiding principles are presented herein. CONCLUSION: Telementoring activities are poised for exponential growth but will require a coordinated effort by stakeholders working through and around a healthcare system not yet suited for this paradigm shift. PMID- 27270589 TI - Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes. AB - Humans with obesity differ in their susceptibility to developing insulin resistance and type 2 diabetes (T2D). This variation may relate to the extent of adipose tissue (AT) inflammation that develops as their obesity progresses. The state of macrophage activation has a central role in determining the degree of AT inflammation and thus its dysfunction, and these states are driven by epigenomic alterations linked to gene expression. The underlying mechanisms that regulate these alterations, however, are poorly defined. Here we demonstrate that a co repressor complex containing G protein pathway suppressor 2 (GPS2) crucially controls the macrophage epigenome during activation by metabolic stress. The study of AT from humans with and without obesity revealed correlations between reduced GPS2 expression in macrophages, elevated systemic and AT inflammation, and diabetic status. The causality of this relationship was confirmed by using macrophage-specific Gps2-knockout (KO) mice, in which inappropriate co-repressor complex function caused enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals. By contrast, transplantation of GPS2-overexpressing bone marrow into two mouse models of obesity (ob/ob and diet induced obesity) reduced inflammation and improved insulin sensitivity. Thus, our data reveal a potentially reversible disease mechanism that links co-repressor dependent epigenomic alterations in macrophages to AT inflammation and the development of T2D. PMID- 27270594 TI - Towards Safer Rocket Fuels: Hypergolic Imidazolylidene-Borane Compounds as Replacements for Hydrazine Derivatives. AB - Currently, toxic and volatile hydrazine derivatives are still the main fuel choices for liquid bipropellants, especially in some traditional rocket propulsion systems. Therefore, the search for safer hypergolic fuels as replacements for hydrazine derivatives has been one of the most challenging tasks. In this study, six imidazolylidene-borane compounds with zwitterionic structure have been synthesized and characterized, and their hypergolic reactivity has been studied. As expected, these compounds exhibited fast spontaneous combustion upon contact with white fuming nitric acid (WFNA). Among them, compound 5 showed excellent integrated properties including wide liquid operating range (-70-160 degrees C), superior loading density (0.99 g cm(-3) ), ultrafast ignition delay times with WFNA (15 ms), and high specific impulse (303.5 s), suggesting promising application potential as safer hypergolic fuels in liquid bipropellant formulations. PMID- 27270595 TI - How do magnitude and frequency of monetary reward guide visual search? AB - How does reward guide spatial attention during visual search? In the present study, we examine whether and how two types of reward information-magnitude and frequency-guide search behavior. Observers were asked to find a target among distractors in a search display to earn points. We manipulated multiple levels of value across the search display quadrants in two ways: For reward magnitude, targets appeared equally often in each quadrant, and the value of each quadrant was determined by the average points earned per target; for reward frequency, we varied how often the target appeared in each quadrant but held the average points earned per target constant across the quadrants. In Experiment 1, we found that observers were highly sensitive to the reward frequency information, and prioritized their search accordingly, whereas we did not find much prioritization based on magnitude information. In Experiment 2, we found that magnitude information for a nonspatial feature (color) could bias search performance, showing that the relative insensitivity to magnitude information during visual search is not generalized across all types of information. In Experiment 3, we replicated the negligible use of spatial magnitude information even when we used limited-exposure displays to incentivize the expression of learning. In Experiment 4, we found participants used the spatial magnitude information during a modified choice task-but again not during search. Taken together, these findings suggest that the visual search apparatus does not equally exploit all potential sources of spatial value information; instead, it favors spatial reward frequency information over spatial reward magnitude information. PMID- 27270596 TI - Where's Icarus? Stigma based on weight that no one wants to see. A candid answer to "A candid discussion of obesity". PMID- 27270597 TI - Ranibizumab in Myopic Choroidal Neovascularization: A Subgroup Analysis by Ethnicity, Age, and Ocular Characteristics in RADIANCE. AB - PURPOSE: To assess the impact of ethnicity, age, and ocular characteristics on ranibizumab efficacy in myopic choroidal neovascularization (CNV). METHODS: In this post hoc subgroup analysis from the phase III RADIANCE study, best-corrected visual acuity (BCVA) outcomes and treatment exposure were analyzed in 105 patients treated with ranibizumab 0.5 mg. Baseline categories included ethnicity, age, baseline BCVA, lesion area, CNV lesion area, refraction sphere, axial length, subretinal fluid, and location of CNV. RESULTS: At month 12, the mean change in BCVA was numerically higher in East-Asians than in Caucasians (17.0 vs. 14.1 letters). The median number of injections varied with ethnicity (East-Asians vs. Caucasians: 2 vs. 3), baseline BCVA (highest vs. lowest: 1 vs. 4), CNV lesion area and lesion area (largest vs. smallest: 5 vs. 1 and 5 vs. 2). CONCLUSIONS: East-Asians showed numerically higher BCVA gains than Caucasians. The number of injections varied across subgroups, emphasizing the need for individualized treatment. PMID- 27270598 TI - Suppression of the motor deficit in a mucolipidosis type IV mouse model by bone marrow transplantation. AB - Mucolipidosis IV (MLIV) is a severe lysosomal storage disorder, which results from loss of the TRPML1 channel. MLIV causes multiple impairments in young children, including severe motor deficits. Currently, there is no effective treatment. Using a Drosophila MLIV model, we showed previously that introduction of trpml+ in phagocytic glia rescued the locomotor deficit by removing early dying neurons, thereby preventing amplification of neuronal death from cytotoxicity. Because microglia, which are phagocytic cells in the mammalian brain, are bone marrow derived, and cross the blood-brain barrier, we used a mouse MLIV model to test the efficacy of bone marrow transplantation (BMT). We found that BMT suppressed the reduced myelination and the increased caspase-3 activity due to loss of TRPML1. Using a rotarod test, we demonstrated that early BMT greatly delayed the motor impairment in the mutant mice. These data offer the possibility that BMT might provide the first therapy for MLIV. PMID- 27270599 TI - Impact of sludge retention time on the fine composition of the microbial community and extracellular polymeric substances in a membrane bioreactor. AB - Membrane bioreactors (MBRs) are an advanced technology for wastewater treatment whose wide application has been hindered by rapid fouling of the membranes. MBRs can be operated with long sludge retention time (SRT), a crucial parameter impacting microbial selection in the reactor. This also affects filtration performance, since a major fouling agent are the extracellular polymeric substances (EPS). In this study, the impact of the SRT on the ecophysiology of the MBRs and, consequently, on membrane fouling was evaluated. A MBR was operated under a SRT of 60 days followed by a SRT of 20 days. A comprehensive analysis of the microbial community structure and EPS proteins and polysaccharide profiles of the mixed liquor and cake layer was carried out throughout both operation periods. The results of this study showed that the imposition of a shorter SRT led to a shift in the dominant bacterial populations. The mixed liquor and cake layer communities were very different, with Actinomycetales order standing out in the cake layer at SRT of 20 days. Overall, higher EPS concentrations (particularly proteins) were found at this SRT. Furthermore, EPS profiles were clearly affected by the SRT: it was possible to correlate a group of soluble EPS proteins with the SRT of 60 days, and a lower sludge age led to a lower diversity of polysaccharide sugar monomers, with an increase of glucose and galactose in the cake layer. This study improves our knowledge regarding the molecular reasons for fouling, which may contribute to improve MBR design and operation. PMID- 27270600 TI - Analysis of coenzyme A activated compounds in actinomycetes. AB - Acyl-CoAs are crucial compounds involved in essential metabolic pathways such as the Krebs cycle and lipid, carbohydrate, and amino acid metabolisms, and they are also key signal molecules involved in the transcriptional regulation of lipid biosynthesis in many organisms. In this study, we took advantage of the high selectivity of mass spectrometry and developed an ion-pairing reverse-phase high pressure liquid chromatography electrospray ionization high-resolution mass spectrometry (IP-RP-HPLC/ESI-HRMS) method to carry on a comprehensive analytical determination of the wide range of fatty acyl-CoAs present in actinomycetes. The advantage of using a QTOF spectrometer resides in the excellent mass accuracy over a wide dynamic range and measurements of the true isotope pattern that can be used for molecular formula elucidation of unknown analytes. As a proof of concept, we used this assay to determine the composition of the fatty acyl-CoA pools in Mycobacterium, Streptomyces, and Corynebacterium species, revealing an extraordinary difference in fatty acyl-CoA amounts and species distribution between the three genera and between the two species of mycobacteria analyzed, including the presence of different chain-length carboxy-acyl-CoAs, key substrates of mycolic acid biosynthesis. The method was also used to analyze the impact of two fatty acid synthase inhibitors on the acyl-CoA profile of Mycobacterium smegmatis, which showed some unexpected low levels of C24 acyl-CoAs in the isoniazid-treated cells. This robust, sensitive, and reliable method should be broadly applicable in the studies of the wide range of bacteria metabolisms in which acyl-CoA molecules participate. PMID- 27270601 TI - The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells. AB - The transcription factor Glis-similar 3 (Glis3) has been implicated in the development of neonatal, type 1 and type 2 diabetes. In this study, we examined the spatiotemporal expression of Glis3 protein during embryonic and neonatal pancreas development as well as its function in PP cells. To obtain greater insights into the functions of Glis3 in pancreas development, we examined the spatiotemporal expression of Glis3 protein in a knockin mouse strain expressing a Glis3-EGFP fusion protein. Immunohistochemistry showed that Glis3-EGFP was not detectable during early pancreatic development (E11.5 and E12.5) and at E13.5 and 15.5 was not expressed in Ptf1a+ cells in the tip domains indicating that Glis3 is not expressed in multipotent pancreatic progenitors. Glis3 was first detectable at E13.5 in the nucleus of bipotent progenitors in the trunk domains, where it co-localized with Sox9, Hnf6, and Pdx1. It remained expressed in preductal and Ngn3+ endocrine progenitors and at later stages becomes restricted to the nucleus of pancreatic beta and PP cells as well as ductal cells. Glis3 deficiency greatly reduced, whereas exogenous Glis3, induced Ppy expression, as reported for insulin. Collectively, our study demonstrates that Glis3 protein exhibits a temporal and cell type-specific pattern of expression during embryonic and neonatal pancreas development that is consistent with a regulatory role for Glis3 in promoting endocrine progenitor generation, regulating insulin and Ppy expression in beta and PP cells, respectively, and duct morphogenesis. PMID- 27270602 TI - The topology of large Open Connectome networks for the human brain. AB - The structural human connectome (i.e. the network of fiber connections in the brain) can be analyzed at ever finer spatial resolution thanks to advances in neuroimaging. Here we analyze several large data sets for the human brain network made available by the Open Connectome Project. We apply statistical model selection to characterize the degree distributions of graphs containing up to nodes and edges. A three-parameter generalized Weibull (also known as a stretched exponential) distribution is a good fit to most of the observed degree distributions. For almost all networks, simple power laws cannot fit the data, but in some cases there is statistical support for power laws with an exponential cutoff. We also calculate the topological (graph) dimension D and the small-world coefficient sigma of these networks. While sigma suggests a small-world topology, we found that D < 4 showing that long-distance connections provide only a small correction to the topology of the embedding three-dimensional space. PMID- 27270603 TI - Deficient Mechanical Activation of Anabolic Transcripts and Post-Traumatic Cartilage Degeneration in Matrilin-1 Knockout Mice. AB - Matrilin-1 (Matn1), a cartilage-specific peri-cellular and extracellular matrix (ECM) protein, has been hypothesized to regulate ECM interactions and transmit mechanical signals in cartilage. Since Matn1 knock-out (Matn1-/-) mice exhibit a normal skeleton, its function in vivo is unclear. In this study, we found that the anabolic Acan and Col2a transcript levels were significantly higher in wildtype (Matn1+/+) mouse cartilage than that of MATN1-/- mice in vivo. However, such difference was not observed between Matn1+/+ and MATN1-/- chondrocytes cultured under stationary conditions in vitro. Cyclic loading significantly stimulated Acan and Col2a transcript levels in Matn1+/+ but not in MATN1-/- chondrocytes. This suggests that, while Matn1+/+ chondrocytes increase their anabolic gene expression in response to mechanical loading, the MATN1-/- chondrocytes fail to do so because of the deficiency in mechanotransduction. We also found that altered elastic modulus of cartilage matrix in Matn1-/- mice, suggesting the mechanotransduction has changed due to the deficiency of Matn1. To understand the impact of such deficiency on joint disease, mechanical loading was altered in vivo by destabilization of medial meniscus. While Matn1+/+ mice exhibited superficial fissures and clefts consistent with mechanical damage to the articular joint, Matn1-/- mice presented more severe cartilage lesions characterized by proteoglycan loss and disorganization of cells and ECM. This suggests that Matn1 deficiency affects pathogenesis of post-traumatic osteoarthritis by failing to up-regulate anabolic gene expression. This is the first demonstration of Matn1 function in vivo, which suggests its protective role in cartilage degeneration under altered mechanical environment. PMID- 27270605 TI - Correction: How Many Parameters Does It Take to Describe Disease Tolerance? AB - [This corrects the article DOI: 10.1371/journal.pbio.1002435.]. PMID- 27270604 TI - Holistic Practice in Traumatic Brain Injury Rehabilitation: Perspectives of Health Practitioners. AB - Given that the literature suggests there are various (and often contradictory) interpretations of holistic practice in brain injury rehabilitation and multiple complexities in its implementation (including complex setting, discipline, and client-base factors), this study aimed to examine the experiences of practitioners in their conceptualization and delivery of holistic practice in their respective settings. Nineteen health practitioners purposively sampled from an extensive Brain Injury Network in Queensland, Australia participated in individual interviews. A systematic text analysis process using Leximancer qualitative analysis program was undertaken, followed by manual thematic analysis to develop overarching themes. The findings from this study have identified several items for future inter-professional development that will not only benefit the practitioners working in brain injury rehabilitation settings, but the patients and their families as well. PMID- 27270606 TI - Folic acid advisories: a public health challenge? AB - Neural tube defects are neurological conditions affecting one in 1000 fetuses in France each year. If a fetus is affected, there is a 90% chance that the pregnancy will be terminated. Increasing folic acid intake to 400MUg per day 2months before and 2months after conception reduces prevalence rates by at least 40%. In 2005, France introduced a social marketing campaign seeking to increase the intake of folic acid by to-be-pregnant and pregnant women through information provision. This paper sets up a quasi-experimental setting to measure the impact of the French social marketing campaign on availability and preferences for folic acid. I combine detailed scanner data on grocery purchases with a dataset on macronutrients and micronutrients. The identification strategy exploits the variation in the usefulness of folic acid information between households: households that are pregnant or want to conceive a child use it, while those that are not pregnant do not. Results suggest evidence of a positive impact of the information campaign on folic acid household availability and preferences. A value per statistical neural tube defects case is found to be of at least 12 million. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270609 TI - Collective and convective effects compete in patterns of dissolving surface droplets. AB - The effects of neighboring droplets on the dissolution of a sessile droplet, i.e. collective effects, are investigated both experimentally and numerically. On the experimental side small approximately 20 nL mono-disperse surface droplets arranged in an ordered pattern were dissolved and their size evolution is studied optically. The droplet dissolution time was studied for various droplet patterns. On the numerical side, lattice-Boltzmann simulations were performed. Both simulations and experiments show that the dissolution time of a droplet placed in the center of a pattern can increase by as much as 60% as compared to a single, isolated droplet, due to the shielding effect of the neighboring droplets. However, the experiments also show that neighboring droplets enhance the buoyancy driven convective flow of the bulk, increasing the mass exchange and counteracting collective effects. We show that this enhanced convection can reduce the dissolution time of droplets at the edges of the pattern to values below that of a single, isolated droplet. PMID- 27270610 TI - Drainage of a complicated high perianal abscess: a bilateral ilioinguinal approach. PMID- 27270607 TI - Hypoxia-inducible factor-targeting prodrug TOP3 combined with gemcitabine or TS-1 improves pancreatic cancer survival in an orthotopic model. AB - Pancreatic cancer is one of the most lethal digestive system cancers with a 5 year survival rate of 4-7%. Despite extensive efforts, recent chemotherapeutic regimens have provided only limited benefits to pancreatic cancer patients. Gemcitabine and TS-1, the current standard-of-care chemotherapeutic drugs for treatment of this severe cancer, have a low response rate. Hypoxia is one of the factors contributing to treatment resistance. Specifically, overexpression of hypoxia-inducible factor, a master transcriptional regulator of cell adaption to hypoxia, is strongly correlated with poor prognosis in many human cancers. TAT ODD-procaspase-3 (TOP3) is a protein prodrug that is specifically processed and activated in hypoxia-inducible factor-active cells in cancers, leading to cell death. Here, we report combination therapies in which TOP3 was combined with gemcitabine or TS-1. As monotherapy, gemcitabine and TS-1 showed a limited effect on hypoxic and starved pancreatic cancer cells, whereas co-treatment with TOP3 successfully overcame this limitation in vitro. Furthermore, combination therapies of TOP3 with these drugs resulted in a significant improvement in survival of orthotopic pancreatic cancer models involving the human pancreatic cancer cell line SUIT-2. Overall, our study indicates that the combination of TOP3 with current chemotherapeutic drugs can significantly improve treatment outcome, offering a promising new therapeutic option for patients with pancreatic cancer. PMID- 27270612 TI - Pneumonia in Children Presenting to the Emergency Department With an Asthma Exacerbation. PMID- 27270613 TI - NIK regulates MT1-MMP activity and promotes glioma cell invasion independently of the canonical NF-kappaB pathway. AB - A growing body of evidence implicates the noncanonical NF-kappaB pathway as a key driver of glioma invasiveness and a major factor underlying poor patient prognoses. Here, we show that NF-kappaB-inducing kinase (NIK/MAP3K14), a critical upstream regulator of the noncanonical NF-kappaB pathway, is both necessary and sufficient for cell-intrinsic invasion, as well as invasion induced by the cytokine TWEAK, which is strongly associated with tumor pathogenicity. NIK promotes dramatic alterations in glioma cell morphology that are characterized by extensive membrane branching and elongated pseudopodial protrusions. Correspondingly, NIK increases the phosphorylation, enzymatic activity and pseudopodial localization of membrane type-1 matrix metalloproteinase (MT1 MMP/MMP14), which is associated with enhanced tumor cell invasion of three dimensional collagen matrices. Moreover, NIK regulates MT1-MMP activity in cells lacking the canonical NF-kappaB p65 and cRel proteins. Finally, increased expression of NIK is associated with elevated MT1-MMP phosphorylation in orthotopic xenografts and co-expression of NIK and MT1-MMP in human tumors is associated with poor glioma patient survival. These data reveal a novel role of NIK to enhance pseudopodia formation, MT1-MMP enzymatic activity and tumor cell invasion independently of p65. Collectively, our findings underscore the therapeutic potential of approaches targeting NIK in highly invasive tumors. PMID- 27270616 TI - Internal electric fields in small water clusters [(H2O)n; n = 2-6]. AB - The electric field experienced by a water molecule within a water cluster depends on its position relative to the rest of the water molecules. The stabilization energies and the red-shifts in the donor O-H stretching vibrations in the water clusters increase with the cluster size concomitant with the increase in the electric field experienced by the donor O-H of a particular water molecule due to the hydrogen bonding network. The red-shifts in O-H stretching frequencies show a spread of about +/-100 cm(-1) against the corresponding electric fields. Deviations from linearity were marked in the region of 100-160 MV cm(-1), which can be attributed to the strain in the hydrogen bonding network, especially for structures with DDAA and DDA motifs. The linear Stark effect holds up to 200 MV cm(-1) of internal electric field for the average red-shifts in the O-H stretching frequencies, with a Stark tuning rate of 2.4 cm(-1) (MV cm(-1))(-1), suggesting the validity of the classical model in small water clusters. PMID- 27270615 TI - Early Mortality Was Highly and Strongly Associated with Functional Status in Incident Japanese Hemodialysis Patients: A Cohort Study of the Large National Dialysis Registry. AB - BACKGROUND: Although dialysis is typically started in an effort to prolong survival, mortality is reportedly high in the first few months. However, it remains unclear whether this is true in Japanese patients who tend to have a better prognosis than other ethnicities, and if health conditions such as functional status (FS) at initiation of dialysis influence prognosis. METHODS: We investigated the epidemiology of early death and its association with FS using Japanese national registry data in 2007, which included 35,415 patients on incident dialysis and 7,664 with FS data. The main outcome was early death, defined as death within 3 months after initiation of hemodialysis (HD). The main predictor was FS at initiation of HD. Levels of functional disability were categorized as follows: severe (bedridden), moderate (overt difficulties in exerting basic activities of daily living), or mild/none (none or some functional disabilities). RESULTS: Early death remained relatively common, especially among elderly patients (overall: 7.1%; those aged >=80 years: 15.8%). Severely and even only a moderately impaired FS were significantly associated with early death after starting dialysis (adjusted risk ratios: 3.93 and 2.38, respectively). The incidence of early death in those with impaired FS increased with age (36.5% in those with severely impaired FS and aged >=80 years). CONCLUSIONS: Early death after starting dialysis was relatively common, especially among the elderly, even in Japanese patients. Further, early death was significantly associated with impaired FS at initiation of HD. PMID- 27270614 TI - PPAR-delta promotes survival of breast cancer cells in harsh metabolic conditions. AB - Expression of the nuclear receptor peroxisome proliferator activated receptor delta (PPARdelta) in breast cancer cells is negatively associated with patient survival, but the underlying mechanisms are not clear. High PPARdelta protein levels in rat breast adenocarcinomas were found to be associated with increased growth in soft agar and mice. Transgenic expression of PPARdelta increased the ability of human breast cancer cell lines to migrate in vitro and form lung metastases in mice. PPARdelta also conferred the ability to grow in exhausted tissue culture media and survive in low-glucose and other endoplasmic reticulum stress conditions such as hypoxia. Upregulation of PPARdelta by glucocorticoids or synthetic agonists also protected human breast cancer cells from low glucose. Survival in low glucose was related to increased antioxidant defenses mediated in part by catalase and also to late AKT phosphorylation, which is associated with the prolonged glucose-deprivation response. Synthetic antagonists reversed the survival benefits conferred by PPARdelta in vitro. These findings suggest that PPARdelta conditions breast cancer cells to survive in harsh microenvironmental conditions by reducing oxidative stress and enhancing survival signaling responses. Drugs that target PPARdelta may have a role in the treatment of breast cancer. PMID- 27270617 TI - Evaluation of Pancreatic Cancer Clinical Trials and Benchmarks for Clinically Meaningful Future Trials: A Systematic Review. AB - IMPORTANCE: Progress in the treatment of pancreatic adenocarcinoma has been minimal; it remains the only major cancer type with a 5-year survival rate of less than 10%. OBJECTIVE: To explore why a large proportion of advanced pancreatic cancer clinical trials executed over the past 25 years have had negative results and to identify benchmarks that could have predicted success. EVIDENCE REVIEW: Phase 3 studies of patients with advanced pancreatic cancer were identified by searching clinicaltrials.gov and the scientific literature. FINDINGS: Thirty-two phase 3 studies in 13 675 chemotherapy-naive patients resulted in 3 agents or combinations being considered clinically meaningful. Nineteen agents or combinations (70%) were tested in phase 2 trials preceding the phase 3 trial. In cases with paired phase 2 and 3 results, meeting the primary end point of the phase 2 trial predicted the outcome of the phase 3 trial 76% of the time but proceeded despite phase 2 negative results in 10 cases. We applied criteria for a clinically meaningful result identified by the American Society of Clinical Oncology (ASCO) Cancer Research Committee to these historical cases. Overall, progression-free and 1-year survival of experimental arms was compared with time period-controlled median values of control arms to normalize for the observed increase in response to gemcitabine over time. CONCLUSIONS AND RELEVANCE: Applying the benchmark of a 50% improvement in overall survival as the primary end point to phase 2 data, or secondary end points of a 90% increase in 1 year survival or an 80% to 100% increase in progression-free survival, showed the greatest ability to predict a clinically meaningful phase 3 trial. Had these criteria been applied to these trials over the past 25 years, more than 11 571 patients enrolled in phase 3 trials that did not meet the primary end point could theoretically have been diverted to earlier-stage trials in an attempt to more rapidly advance the field. PMID- 27270628 TI - Use of Electronic Medication Administration Records to Reduce Perceived Stress and Risk of Medication Errors in Nursing Homes. AB - Concerns have been raised about the effects of current medication administration processes on the safety of many of the aspects of medication administration. Keeping electronic medication administration records could decrease many of these problems. Unfortunately, there has not been much research on this topic, especially in nursing homes. A prospective case-control survey was consequently performed at two nursing homes; the electronic record system was introduced in one, whereas the other continued to use paper records. The personnel were asked to fill in a questionnaire of their perceptions of stress and risk of medication errors at baseline (n = 66) and 20 weeks after the intervention group had started recording medication administration electronically (n = 59). There were statistically significant decreases in the perceived risk of omitting a medication, of medication errors occurring because of communication problems, and of medication errors occurring because of inaccurate medication administration records in the intervention group (all P < .01 vs the control group). The perceived overall daily stress levels were also reduced in the intervention group (P < .05). These results indicate that the utilization of electronic medication administration records will reduce many of the concerns regarding the medication administration process. PMID- 27270629 TI - Use of Data Mining to Predict the Risk Factors Associated With Osteoporosis and Osteopenia in Women. AB - Osteoporosis has recently been acknowledged as a major public health issue in developed countries because of the decrease in the quality of life of the affected person and the increase in public costs due to complete or partial physical disability. The aim of this study was to use the J48 algorithm as a classification task for data from women exhibiting changes in bone densitometry. The study population included all patients treated at the diagnostic center for bone densitometry since 2010. Census sample data collection was conducted as all elements of the population were included in the sample. The service in question provides care to patients via the Brazilian Unified Health System and private plans. The results of the classification task were analyzed using the J48 algorithm, and among the dichotomized variables associated with a diagnosis of osteoporosis, the mean accuracy was 74.0 (95% confidence interval [CI], 61.0 68.0) and the mean area under the curve of the receiver operating characteristic (ROC) curve was 0.65 (95% CI, 0.64-0.66), with a mean sensitivity of 76.0 (95% CI, 76.0-76.0) and a mean specificity of 48.0 (95% CI, 46.0-49.0). The analyzed results showed higher values of sensitivity, accuracy, and curve of the ROC area in experiments conducted with individuals with osteoporosis. Most of the generated rules were consistent with the literature, and the few differences might serve as hypotheses for further studies. PMID- 27270627 TI - Genome-Wide Association Study of Anthracnose Resistance in Andean Beans (Phaseolus vulgaris). AB - Anthracnose is a seed-borne disease of common bean (Phaseolus vulgaris L.) caused by the fungus Colletotrichum lindemuthianum, and the pathogen is cosmopolitan in distribution. The objectives of this study were to identify new sources of anthracnose resistance in a diverse panel of 230 Andean beans comprised of multiple seed types and market classes from the Americas, Africa, and Europe, and explore the genetic basis of this resistance using genome-wide association mapping analysis (GWAS). Twenty-eight of the 230 lines tested were resistant to six out of the eight races screened, but only one cultivar Uyole98 was resistant to all eight races (7, 39, 55, 65, 73, 109, 2047, and 3481) included in the study. Outputs from the GWAS indicated major quantitative trait loci (QTL) for resistance on chromosomes, Pv01, Pv02, and Pv04 and two minor QTL on Pv10 and Pv11. Candidate genes associated with the significant SNPs were detected on all five chromosomes. An independent QTL study was conducted to confirm the physical location of the Co-1 locus identified on Pv01 in an F4:6 recombinant inbred line (RIL) population. Resistance was determined to be conditioned by the single dominant gene Co-1 that mapped between 50.16 and 50.30 Mb on Pv01, and an InDel marker (NDSU_IND_1_50.2219) tightly linked to the gene was developed. The information reported will provide breeders with new and diverse sources of resistance and genomic regions to target in the development of anthracnose resistance in Andean beans. PMID- 27270630 TI - Designing Computerized Provider Order Entry Software in Iran: The Nurses' and Physicians' Viewpoints. AB - This study aimed to identify the functional requirements of computerized provider order entry software and design this software in Iran. This study was conducted using review documentation, interview, and focus group discussions in Shiraz University of Medical Sciences, as the medical pole in Iran, in 2013-2015. The study sample consisted of physicians (n = 12) and nurses (n = 2) in the largest hospital in the southern part of Iran and information technology experts (n = 5) in Shiraz University of Medical Sciences. Functional requirements of the computerized provider order entry system were examined in three phases. Finally, the functional requirements were distributed in four levels, and accordingly, the computerized provider order entry software was designed. The software had seven main dimensions: (1) data entry, (2) drug interaction management system, (3) warning system, (4) treatment services, (5) ability to write in software, (6) reporting from all sections of the software, and (7) technical capabilities of the software. The nurses and physicians emphasized quick access to the computerized provider order entry software, order prescription section, and applicability of the software. The software had some items that had not been mentioned in other studies. Ultimately, the software was designed by a company specializing in hospital information systems in Iran. This study was the first specific investigation of computerized provider order entry software design in Iran. Based on the results, it is suggested that this software be implemented in hospitals. PMID- 27270631 TI - Midwives and the Computerization of Perinatal Data Entry: The Theory of Beneficial Engagement. AB - Theory building in nursing and midwifery both to explain and inform practice is important to advance these professions via provision of a theoretical foundation. This research explored the process of perinatal data entry undertaken by midwives to explore the impact of the movement from paper to computer collection of data. Use of grounded theory methodology enabled theory building, leading to a theoretical understanding of the phenomenon and development of the Theory of Beneficial Engagement grounded in the data. Methods involved in-depth semistructured interviews with 15 users of perinatal data systems. Participants were recruited from 12 different healthcare locations and were utilizing three different electronic systems for data entry. The research question that guided the study focused on examining the influences of using the computer for perinatal data entry. Findings indicated that qualities particular to some midwives denoted engagement with perinatal data entry, suggesting a strong desire to enter complete, timely, and accurate data. The Theory of Beneficial Engagement provides a model of user engagement with systems for perinatal data entry consistent with other theories of engagement. The theory developed describes this phenomenon in a simple, elegant manner that can be applied to other areas where mandatory data entry is undertaken. PMID- 27270632 TI - A Formative Program Evaluation of Electronic Clinical Tracking System Documentation to Meet National Core Competencies. AB - Electronic clinical tracking systems are used in many educational institutions of higher learning to document advanced practice registered nursing students' clinical experiences. Students' clinical experiences are constructed according to the National Organization of Nurse Practitioner Faculties core competencies. These competencies form a basis for evaluation of advanced practice registered nursing programs. However, no previous studies have evaluated the use of electronic clinical tracking systems to validate students' clinical experiences in meeting national core competencies. Medatrax, an electronic clinical tracking system, is evaluated using a formative program evaluation approach to determine if students' clinical documentations meet Family/Across the Lifespan Nurse Practitioner Competencies in a midsouthern family nurse practitioner program. This formative program evaluation supports the use of an electronic clinical tracking system in facilitating accreditation and program outcome goals. The significance of this study is that it provides novel evidence to support the use of an electronic clinical tracking system to assist a midsouthern school of nursing in meeting national core competencies. PMID- 27270633 TI - NiCo nanoalloy encapsulated in graphene layers for improving hydrogen storage properties of LiAlH4. AB - NiCo nanoalloy (4-6 nm) encapsulated in grapheme layers (NiCo@G) has been prepared by thermolysis of a 3D bimetallic complex CoCo[Ni(EDTA)]2.4H2O and successfully employed as a catalyst to improve the dehydrogenation performances of LiAlH4 by solid ball-milling. NiCo@G presents a superior catalytic effect on the dehydrogenation of LiAlH4. For LiAlH4 doped with 1 wt% NiCo@G (LiAlH4-1 wt% NiCo@G), the onset dehydrogenation temperature of LiAlH4 is as low as 43 degrees C, which is 109 degrees C lower than that of pristine LiAlH4. 7.3 wt% of hydrogen can be released from LiAlH4-1 wt% NiCo@G at 150 degrees C within 60 min. The activation energies of LiAlH4 dehydrogenation are extremely reduced by 1 wt% NiCo@G doping. PMID- 27270634 TI - Monolithically, widely tunable quantum cascade lasers based on a heterogeneous active region design. AB - Quantum cascade lasers (QCLs) have become important laser sources for accessing the mid-infrared (mid-IR) spectral range, achieving watt-level continuous wave operation in a compact package at room temperature. However, up to now, wavelength tuning, which is desirable for most applications, has relied on external cavity feedback or exhibited a limited monolithic tuning range. Here we demonstrate a widely tunable QCL source over the 6.2 to 9.1 MUm wavelength range with a single emitting aperture by integrating an eight-laser sampled grating distributed feedback laser array with an on-chip beam combiner. The laser gain medium is based on a five-core heterogeneous QCL wafer. A compact tunable laser system was built to drive the individual lasers within the array and produce any desired wavelength within the available spectral range. A rapid, broadband spectral measurement (520 cm(-1)) of methane using the tunable laser source shows excellent agreement to a measurement made using a standard low-speed infrared spectrometer. This monolithic, widely tunable laser technology is compact, with no moving parts, and will open new opportunities for MIR spectroscopy and chemical sensing. PMID- 27270635 TI - Gender Dysphoria in a 62-Year-Old Genetic Female With Congenital Adrenal Hyperplasia. AB - We report a case of gender dysphoria (GD) in a 62-year-old genetic female patient, raising the pros and cons of performing corrective surgery later in life. This 46,XX DSD patient was registered and reared as a girl; CAH was diagnosed late in childhood. Poor adherence to treatment and lack of proper psychological management contributed to evident GD. Living for years as a male, the patient applied for a legitimate male identification document in his late 50s; thereafter, he requested a sex-reassignment surgery "to disguise his female body upon his death." We informed the patient and family about surgery hazards, while analytical therapy allowed the group to evaluate the actual wish for surgery. When the wish was brought up, the role of death urged the group to rethink the course of treatment. During the process, it became clear that the patient's desire for surgery, more than a wish for changing the genitalia, expressed an impulse related to issues of endorsement and acceptance of his male identity. This report raises interesting questions about sexuality in a social context and prompts the idea that sexuality is broader than sex itself, raising new questions on the psychological risks faced when considering a body change after years of living with a disorder of sex development. PMID- 27270637 TI - Macrophage Inhibition Factor-Mediated CD74 Signal Modulate Inflammation and Matrix Metabolism in the Degenerated Cartilage Endplate Chondrocytes by Activating Extracellular Signal Regulated Kinase 1/2. AB - STUDY DESIGN: The macrophage inhibition factor (MIF)-mediated CD74 dependent extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were associated with inflammatory activity and matrix metabolism in human degenerated cartilage endplate (CEP). Anabolic/catabolic factors in pathogenesis of CEP degeneration were evaluated. OBJECTIVE: To study the effect of MIF-mediated CD74 dependent ERK1/2 activation on the CEP degeneration. SUMMARY OF BACKGROUND DATA: MIF-CD74 signal is closely related to the CEP degeneration by inducing the secretion of inflammatory cytokines. ERK1/2-mediated inflammatory pathway also plays a crucial role in the intervertebral disc degeneration. The role of the ERK1/2 pathway in CEP chondrocytes response to MIF-CD74 signal has, however, not been fully elucidated. METHODS: Chondrocytes were exposed to MIF, with or without ERK1/2 inhibition; CD74 interfered chondrocytes were also exposed to MIF, with or without ERK inhibition. mRNAs were isolated for real-time polymerase chain reaction measurement of gene expression. Western blotting was carried out to analyze the protein expression. RESULTS: ERK1/2 expression was significantly increased by MIF. MIF modulates metabolism in CEP chondrocytes and decreased by its inhibitor PD98059. ERK1/2 expression was significantly decreased by CD74siRNA. Inflammatory cytokines expression was significantly increased by MIF induced ERK1/2 activation and significantly suppressed by PD98059. On the contrary, matrix expression was significantly decreased by MIF-induced ERK1/2 activation and reversed by PD98059. CD74siRNA decreased the CD74 expression in chondrocytes. Inflammatory cytokines and matrix expression were not induced by MIF in CD74 interfered chondrocytes. CONCLUSION: These results show that MIF-CD74 signal elicits an imbalance between anabolic and catabolic metabolism in CEP chondrocytes via ERK signal pathway. ERK inhibition could exert therapeutic effect against the harmful effects of MIF-CD74 signal in CEP degeneration. LEVEL OF EVIDENCE: N/A. PMID- 27270638 TI - Patient-Induced Reaction Forces and Moments Are Influenced by Variations in Spinal Manipulative Technique. AB - STUDY DESIGN: An in vivo biomechanical study. OBJECTIVE: The aim of the present study was to quantify and compare the reaction loads for two spinal manipulation therapy (SMT) procedures commonly used for low back pain using a biomechanical computer model. SUMMARY OF BACKGROUND DATA: Contemporary computer-driven rigid linked-segment models (LSMs) have made it feasible to analyze low back kinetics and kinematics during various activities including SMT procedures. Currently, a comprehensive biomechanical model analyzing actual differences in loading effects between different SMT procedures is lacking. METHODS: Twenty-four healthy/asymptomatic participants received a total of six SMT applications, representing all combinations of two similar SMT procedures within three patient hip flexion angles. All contact forces, patient torso kinematics, and inertial properties were entered into a dynamic three-dimensional LSM to calculate lumbar reaction forces and moments. Peak net applied force along with the maximums, minimums, and ranges for each component of the three-dimensional reaction force and moment vectors during each SMT procedure was analyzed. RESULTS: One specific SMT technique (lumbar spinous pull) produced greater maximum anterior-posterior reaction force and both lateral bending and axial twisting reaction moments compared to the other technique (lumbar push procedure [all P <= 0.034]). SMT trials without hip flexion had lower maximum medial-lateral reaction force and range compared to those with 45 and 90 degrees of hip flexion (all P <= 0.041). There were no interactions between procedure and hip angle for any of the dependent measurements. CONCLUSION: The technique used to apply SMT and the participant's initial hip orientation induced significantly different actions on the low back. These findings and future research can improve patient outcomes and safety by informing clinicians on how to best use SMT given specific types of low back pain. LEVEL OF EVIDENCE: 2. PMID- 27270639 TI - Spinal Epidural Hematoma Due To Tyre-Blast Injury: A Case Report. AB - STUDY DESIGN: A retrospective case report. OBJECTIVE: The objective of this article is to report a spinal epidural hematoma (SEH) due to shock wave. SUMMARY OF BACKGROUND DATA: SEH is an infrequent condition. Most of SEH's are spontaneous. We have reported an SEH traumatic case without bone lesions due to exploding truck tire. A different category of blast injuries is the one related with exploding tyres. Shock waves are the main mechanism that is responsible for blast injuries. We are presenting the first report of acute SEH due to shock wave. METHODS: A 33-year-old man was brought to the emergency department with complaints of weakness and numbness of the upper extremities. There was an epidural high-signal density without osseous lesion in computerized tomography from the level of C2 to C5, and there was a T2-weighted hyperintense lesion in magnetic resonance imaging from the level of C2 to C5 with compression of the spinal cord the anterior and posterior which proved to be an SEH. RESULTS: The patient was discharged from the hospital with complete neurologic recovery. CONCLUSION: SEH should be considered possible in the blast injury. SEH condition carries a significant risk of morbidity and mortality without early recognition and rapid management. LEVEL OF EVIDENCE: 5. PMID- 27270640 TI - Risk Factors of Adjacent Segment Disease After Transforaminal Inter-Body Fusion for Degenerative Lumbar Disease. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study was to determine the incidence and risk factors of adjacent segment disease (ASD) after transforaminal inter-body fusion (TLIF) for degenerative lumbar disease. SUMMARY OF BACKGROUND DATA: ASD is a major complication after spinal fusion. Many reports have been published concerning the risk factors for ASD after TLIF. A number of quantitative relationships to spino-pelvic parameters have been established. A retrospective cohort study was carried out to investigate spino-pelvic alignment in patients with ASD after TLIF. METHODS: This study evaluated 263 subjects (150 subjects undergoing floating fusion (FF group), and 113 patients undergoing lumbosacral fusion (LF group)) who underwent TLIF from 2009 to 2012. The mean follow-up period was 37.6 months. Several parameters were measured using pre- and postoperative full-length free-standing radiographs, including lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), and PI-LL. Multivariate logistic regression analysis was performed to evaluate these parameters as potential risk factors of early onset radiographic ASD. RESULTS: Radiographic ASD was found in 65 cases (43.3%) in the FF group, and 49 cases (43.3%) in the LF group. LL improved by 7.5 degrees and 3.9 degrees in each group respectively after TLIF. However, PT worsened by 6.4 degrees in the LF group. When comparing with ASD positive cases and ASD negative cases, a significant difference in preoperative PT was observed in both FF (P = 0.001) and LF groups (P = 0.0001). Logistic regression analysis and receiver operating characteristic analysis revealed that preoperative PT of more than 22.5 degrees was a significant risk factor of the incidence of ASD after TLIF (P = 0.02; odds ratio: 5.1, 95% CI: 1.62-9.03). CONCLUSION: Patients with preoperative sagittal imbalance have a statistically significant increased risk of ASD. The risk of ASD incidence was 5.1 times greater in subjects with preoperative PT of more than 22.5 degrees . PMID- 27270636 TI - Up-regulation of Siah1 by ethanol triggers apoptosis in neural crest cells through p38 MAPK-mediated activation of p53 signaling pathway. AB - Seven in absentia homolog 1 (Siah1) is one of the E3 ubiquitin ligases and plays a key role in regulating target protein degradation. This study was designed to test the hypothesis that Siah1 mediates ethanol-induced apoptosis in NCCs through p38 MAPK-mediated activation of the p53 signaling pathway. We found that exposure of NCCs to ethanol resulted in the increases in the total protein levels of p53 and the phosphorylation of p53 at serine 15. Ethanol exposure also resulted in a significant increase in the phosphorylation of p38 MAPK. Knock-down of Siah1 dramatically reduced the ethanol-induced increase in the phosphorylation of p38 MAPK. Knock-down of Siah1 by siRNA or down-regulation of p38 MAPK by either siRNA or inhibitor significantly diminished ethanol-induced accumulations of p53 and the phosphorylation of p53. In addition, ethanol exposure resulted in a significant increase in the expression of p53 downstream targets and apoptosis in NCCs, which can be significantly diminished by down-regulation of Siah1 with siRNA. Knock-down of p38 MAPK by siRNA also dramatically reduced the ethanol induced apoptosis. These results demonstrate that Siah1 plays a crucial role in ethanol-induced apoptosis in NCCs, and that the up-regulation of Siah1 by ethanol can trigger apoptosis through p38 MAPK-mediated activation of the p53 signaling pathway. PMID- 27270641 TI - Cost-Effectiveness of Primary Care Management With or Without Early Physical Therapy for Acute Low Back Pain: Economic Evaluation of a Randomized Clinical Trial. AB - STUDY DESIGN: Economic evaluation of a randomized clinical trial. OBJECTIVE: Compare costs and cost-effectiveness of usual primary care management for patients with acute low back pain (LBP) with or without the addition of early physical therapy. SUMMARY OF BACKGROUND DATA: Low back pain is among the most common and costly conditions encountered in primary care. Early physical therapy after a new primary care consultation for acute LBP results in small clinical improvement but cost-effectiveness of a strategy of early physical therapy is unknown. METHODS: Economic evaluation was conducted alongside a randomized clinical trial of patients with acute, nonspecific LBP consulting a primary care provider. All patients received usual primary care management and education, and were randomly assigned to receive four sessions of physical therapy or usual care of delaying referral consideration to permit spontaneous recovery. Data were collected in a randomized trial involving 220 participants age 18 to 60 with LBP <16 days duration without red flags or signs of nerve root compression. The EuroQoL EQ-5D health states were collected at baseline and after 1-year and used to compute the quality adjusted life year (QALY) gained. Direct (health care utilization) and indirect (work absence or reduced productivity) costs related to LBP were collected monthly and valued using standard costs. The incremental cost effectiveness ratio was computed as incremental total costs divided by incremental QALYs. RESULTS: Early physical therapy resulted in higher total 1 year costs (mean difference in adjusted total costs = $580, 95% CI: $175, $984, P = 0.005) and better quality of life (mean difference in QALYs = 0.02, 95% CI: 0.005, 0.35, P = 0.008) after 1-year. The incremental cost-effectiveness ratio was $32,058 (95% CI: $10,629, $151,161) per QALY. CONCLUSION: Our results support early physical therapy as cost-effective relative to usual primary care after 1 year for patients with acute, nonspecific LBP. LEVEL OF EVIDENCE: 2. PMID- 27270643 TI - Early Signs of End-Organ Damage in Retinal Arterioles in Patients with Type 2 Diabetes Compared to Hypertensive Patients. AB - BACKGROUND: Eutrophic and hypertrophic remodeling are major vascular hallmarks for hypertension and diabetes-associated microvascular end-organ damage in peripheral arterioles. The aim of this study is to compare retinal arterioles of diabetic, hypertensive, and healthy individuals. METHODS: Retinal parameters were assessed in 99 patients with T2DM, 158 hypertensive, and 149 healthy individuals. WT and CA of retinal arterioles (80-140 MUm) were measured noninvasively and in vivo by scanning laser Doppler flowmetry (Heidelberg Engineering, Germany). RESULTS: After adjustment for values differing between the groups (age, BMI, gender, HDL cholesterol and serum creatinine, systolic office BP), patients with T2DM showed no significant difference in WT (14.2 +/- 3), and CA (4199 +/- 1107) in comparison with hypertensive patients (WT = 13.3 +/- 4, p = 0.18, CA = 3862 +/ 1546, p = 0.10) and healthy individuals (WT = 13.1 +/- 3, p = 0.55, CA = 3864 +/ 1216, p = 0.86). However, the subgroup of patients with diabetes duration of more than 60 months showed greater WT (14.9 +/- 4, p = 0.04) and CA (4557 +/- 1137, p = 0.02) than the hypertensive group and greater WT (p = 0.04) and CA (p = 0.03) than the healthy group, which is consistent with hypertrophic remodeling. CONCLUSION: In the early stage of T2DM no hypertrophic remodeling was seen in retinal arterioles. However, hypertrophic remodeling was found in diabetic patients with more than 60 months duration of disease. PMID- 27270644 TI - Cost-utility analysis of magnetoencephalography used to inform intracranial electrode placement in patients with drug resistant epilepsy: a model based analysis. AB - OBJECTIVES: We estimated the cost-effectiveness of adding magnetoencephalography to a standard assessment for epilepsy surgery consisting of neuropsychology, magnetic resonance imagining, scalp electroencephalography, video electroencephalography and intracranial electroencephalography, in the capacity of informing intracranial electroencephalography electrode placement. METHODS: We used Microsoft Excel (2007) to construct a decision model. Discounted costs and quality adjusted life years are aggregated to calculate incremental cost effectiveness ratios. Sensitivity analyses are conducted to assess robustness of findings. RESULTS: Our base case analysis yielded a result of $14 300 per quality adjusted life year gained. A total of 82.7% of probabilistic sensitivity analysis iterations resulted in incremental cost-effectiveness ratios below $100 000 in 2014 Canadian dollars. CONCLUSIONS: Our findings demonstrate that the inclusion of Magnetoencephalography in the assessment for epilepsy surgery in the capacity of informing intracranial electroencephalography electrode placement is likely not cost saving but does represent a reasonable allocation of resources from a value for money perspective. PMID- 27270645 TI - Enhanced vocational rehabilitation for Veterans with mild traumatic brain injury and mental illness: Pilot study. AB - Work plays a significant role in how people identify themselves, and successful return to work is associated with significant psychological and rehabilitative benefits. Unfortunately, despite the many benefits of employment, Veterans who experience mild traumatic brain injury and have mental health issues often have significant difficulty getting their vocational needs met. Considering that a consistent relationship between cognitive dysfunction and difficulties with employability has been firmly established, cognitive rehabilitation may enhance engagement in vocational rehabilitation and return to work outcomes. In this pilot study, we evaluated a 12 wk cognitive rehabilitation intervention embedded within vocational rehabilitation services. Eighteen Veterans were randomly assigned to receive either the embedded cognitive rehabilitation intervention (n = 10) or a control condition offering supportive client-centered therapy that did not focus on employment or cognitive rehabilitation (n = 8); all Veterans (intervention and control groups) received vocational rehabilitation services. This pilot feasibility study demonstrated efficient implementation of an embedded cognitive rehabilitation intervention within vocational rehabilitation. The current pilot data revealed small to moderate effect sizes on employment outcomes. Given these preliminary findings, a larger outcome study is warranted. PMID- 27270646 TI - Lymphatic endothelial cells attenuate inflammation via suppression of dendritic cell maturation. AB - Vascular endothelial growth factor-C (VEGF-C)-induced lymphangiogenesis and increased tissue drainage have been reported to inhibit acute and chronic inflammation, and an activated lymphatic endothelium might mediate peripheral tolerance. Using transgenic mice overexpressing VEGF-C in the skin, we found that under inflammatory conditions, VEGF-C-mediated expansion of the cutaneous lymphatic network establishes an immune-inhibitory microenvironment characterised by increased regulatory T (Treg) cells, immature CD11c+CD11b+ dendritic cells (DCs) and CD8+ cells exhibiting decreased effector function. Strikingly, lymphatic endothelial cell (LEC)-conditioned media (CM) potently suppress DC maturation with reduced expression of MHCII, CD40, and IL-6, and increased IL-10 and CCL2 expression. We identify an imbalance in prostaglandin synthase expression after LEC activation, favoring anti-inflammatory prostacyclin synthesis. Importantly, blockade of LEC prostaglandin synthesis partially restores DC maturity. LECs also produce TGF-beta1, contributing to the immune inhibitory microenvironment. This study identifies novel mechanisms by which the lymphatic endothelium modulates cellular immune responses to limit inflammation. PMID- 27270649 TI - Targeting microenvironment in cancer therapeutics. AB - During development of a novel treatment for cancer patients, the tumor microenvironment and its interaction with the tumor cells must be considered. Aspects such as the extracellular matrix (ECM), the epithelial-mesenchymal transition (EMT), secreted factors, cancer-associated fibroblasts (CAFs), the host immune response, and tumor-associated microphages (TAM) are critical for cancer progression and metastasis. Additionally, signaling pathways such as the nuclear factor kappaB (NF-kappaB), transforming growth factor beta (TGFbeta), and tumor necrosis factor alpha (TNFalpha) can promote further cytokine release in the tumor environment, and impact tumor progression greatly. Importantly, cytokine overexpression has been linked to drug resistance in cancers and is therefore an attractive target for combinational therapies. Specific inhibitors of cytokines involved in signaling between tumor cells and the microenvironment have not been studied in depth and have great potential for use in personalized medicines. Together, the interactions between the microenvironment and tumors are critical for tumor growth and promotion and should be taken into serious consideration for future novel therapeutic approaches. PMID- 27270650 TI - TCF21 genetic polymorphisms and breast cancer risk in Chinese women. AB - Transcription factor 21 (TCF21) functions as a tumor suppressor and is inactivated in several types of cancer. The purpose of this study is to investigate whether TCF21 genetic polymorphisms(rs2327429 T>C, rs2327430 T>C, rs2327433 A>G, rs12190287 C>G, rs7766238 G>A, rs4896011 T>A) are associated with the risk of breast cancer in Chinese women. Logistic regression analyses showed that TCF21 rs12190287 polymorphism was significantly associated with the reduced risk of breast cancer. Stratified analyses based on pathological type indicated that TCF21 rs12190287 polymorphism was only associated with the reduced risk of infiltrative ductal carcinoma. Real-time quantitative PCR analyses revealed that compared with those carrying rs12190287 CC genotype, subjects with GG genotype had higher expression levels of TCF21 mRNA in normal breast tissues. Furthermore, luciferase activity assay showed that the rs12190287 G allele weakened the binding affinity of hsa-miR-224 to TCF21 3' UTR. These findings suggest that TCF21 rs12190287 polymorphism can regulate TCF21 expression and may serve as a potential marker for genetic susceptibility to breast cancer. PMID- 27270648 TI - Intrinsic resistance to PIM kinase inhibition in AML through p38alpha-mediated feedback activation of mTOR signaling. AB - Although conventional therapies for acute myeloid leukemia (AML) and diffuse large B-cell lymphoma (DLBCL) are effective in inducing remission, many patients relapse upon treatment. Hence, there is an urgent need for novel therapies. PIM kinases are often overexpressed in AML and DLBCL and are therefore an attractive therapeutic target. However, in vitro experiments have demonstrated that intrinsic resistance to PIM inhibition is common. It is therefore likely that only a minority of patients will benefit from single agent PIM inhibitor treatment. In this study, we performed an shRNA-based genetic screen to identify kinases whose suppression is synergistic with PIM inhibition. Here, we report that suppression of p38alpha (MAPK14) is synthetic lethal with the PIM kinase inhibitor AZD1208. PIM inhibition elevates reactive oxygen species (ROS) levels, which subsequently activates p38alpha and downstream AKT/mTOR signaling. We found that p38alpha inhibitors sensitize hematological tumor cell lines to AZD1208 treatment in vitro and in vivo. These results were validated in ex vivo patient derived AML cells. Our findings provide mechanistic and translational evidence supporting the rationale to test a combination of p38alpha and PIM inhibitors in clinical trials for AML and DLBCL. PMID- 27270651 TI - Age-related increase of thromboxane B2 and risk of cardiovascular disease in atrial fibrillation. AB - Aging is strictly associated with an increased incidence of cardiovascular events (CVEs) in the general population. Mechanisms underlying the risk of CVEs are still unclear. Platelet activation contributes to the onset of cardiovascular complications. The incidence of atrial fibrillation (AF) increases with age, and the natural history of AF is often complicated by CVEs. We prospectively investigated the relationship between age, urinary thromboxane (Tx) B2, which reflects platelet activation, and CVEs in 833 AF patients. Median TxB2 level was 120 [66-200] ng/mg of urinary creatinine. At multivariable linear regression analysis, age (B: 0.097, p=0.005) and previous MI/CHD (B: 0.069, p=0.047) were associated with log-TxB2 levels. When we divided our population into age classes (i.e. < 60, 60-69, 70-79, >= 80 years), we found a significant difference in TxB2 levels across classes (p=0.005), with a significant elevation at 74.6 years. During a mean follow-up of 40.9 months, 128 CVEs occurred; the rate of CVEs significantly increased with age classes (Log-rank test, p < 0.001). TxB2 levels were higher in patients with, compared to those without, CVEs in patients aged 70 79 (p < 0.001) and >= 80 (p = 0.020) years. In conclusion, TxB2 levels enhance by increasing age, suggesting that platelet activation contributes to CVEs in elderly patients with AF. PMID- 27270652 TI - Loss of TGFbeta signaling promotes colon cancer progression and tumor-associated inflammation. AB - TGFbeta has both tumor suppressive and tumor promoting effects in colon cancer. Also, TGFbeta can affect the extent and composition of inflammatory cells present in tumors, contextually promoting and inhibiting inflammation. While colon tumors display intratumoral inflammation, the contributions of TGFbeta to this process are poorly understood. In human patients, we found that epithelial loss of TGFbeta signaling was associated with increased inflammatory burden; yet overexpression of TGFbeta was also associated with increased inflammation. These findings were recapitulated in mutant APC models of murine tumorigenesis, where epithelial truncation of TGFBR2 led to lethal inflammatory disease and invasive colon cancer, mediated by IL8 and TGFbeta1. Interestingly, mutant APC mice with global suppression of TGFbeta signals displayed an intermediate phenotype, presenting with an overall increase in IL8-mediated inflammation and accelerated tumor formation, yet with a longer latency to the onset of disease observed in mice with epithelial TGFBR-deficiency. These results suggest that the loss of TGFbeta signaling, particularly in colon epithelial cells, elicits a strong inflammatory response and promotes tumor progression. This implies that treating colon cancer patients with TGFbeta inhibitors may result in a worse outcome by enhancing inflammatory responses. PMID- 27270653 TI - Association of FCGR2A rs1801274 polymorphism with susceptibility to autoimmune diseases: A meta-analysis. AB - OBJECTIVES: The aim of this meta-analysis was to estimate the association between the FCGR2A rs1801274 polymorphism and the susceptibility to autoimmune diseases more precisely. METHODS: A meta-analysis was conducted on the association between the FCGR2A gene variants and ADs by allelic contrast, homozygote contrast, the recessive model, and the dominant model. RESULTS: A total of 17 studies with 30 comparisons in different populations and genotype-methods were available for this meta-analysis, including 10 Kawasaki disease (KD), 7 Ulcerative colitis (UC), 6 Crohn's disease (CD), 3 Rheumatoid arthritis (RA), 2 Systemic lupus erythematosus (SLE), 1 Autoimmune thyroid disease (ATD) and 1 diabetes mellitus type 1 (T1D). A significant association between FCGR2A rs1801274 polymorphism were found in KD (OR = 1.409, P < 0.001) and UC (OR = 1.237, P < 0.001). A overall meta-analysis increased risk of AD significant association between FCGR2A rs1801274 gene polymorphism and ADs under allelic (OR = 1.378, P=0.000), homozygous (OR: 1.866, P=0.001), dominant (OR = 1.667, P = 0.000) and recessive (OR = 1.434, P=0.000) in Asian population. Meanwhile, a decreased risk of AD was detected in the allelic (OR= 0.882, P = 0.011), homozygous (OR = 0.777, P = 0.013), dominant (OR = 0.850, P = 0.032) and recessive (OR = 0.840, P = 0.048) in African-American population. CONCLUSIONS: This meta-analysis demonstrates that the FCGR2A rs1801274 G-allele confers susceptibility to KD and UC. Data also suggests that the FCGR2A rs1801274 polymorphism may be associated with the susceptibility of multiple ADs in Asian and African-American populations. PMID- 27270647 TI - Mitochondrial dysfunction and oxidative stress in aging and cancer. AB - Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype. PMID- 27270655 TI - Meta-analysis of the efficacy of the pretreatment neutrophil-to-lymphocyte ratio as a predictor of prognosis in renal carcinoma patients receiving tyrosine kinase inhibitors. AB - The data on the impact of the neutrophil-to-lymphocyte ratio (NLR) in metastatic renal cell carcinoma (mRCC) patients receiving tyrosine kinase inhibitors (TKIs) are inconsistent. We therefore performed a meta-analysis to assess the prognostic value of pretreatment NLR in patients treated with TKIs for mRCC. We searched the Embase, Medline, PubMed, Cochrane and ISI Web of Knowledge to identify clinical studies that had evaluated the association between the pretreatment NLR and prognosis in mRCC patients. Prognostic outcomes included overall survival (OS) and progression-free survival (PFS). Nine studies encompassing a total of 1091 participants were included. We found that a high NLR was an effective prognostic marker of both OS (pooled HR: 1.93, 95% CI: 1.35-2.77; P = 0.0003) and PFS (pooled HR: 2.12, 95% CI: 1.42-3.17; P = 0.0002). Subgroup analysis revealed that studies reporting a NLR >= 3 showed a more significant effect of NLR on both OS (pooled HR: 2.50, 95% CI: 1.99-3.14; P = 0.0003) and PFS (pooled HR: 2.17, 95% CI: 1.26-3.75). This meta-analysis suggests that high pretreatment NLR is associated with a poor prognosis in mRCC patients receiving TKI treatment. PMID- 27270656 TI - The prognostic value of lymph nodes count on survival of patients with node negative gastric cancer. AB - The retrieved lymph node (LN) count has been validated as a prognostic factor in various cancers. However, the interaction between LN counts and patients' prognosis in gastric cancer with negative-LN metastasis is not fully studied. Surveillance, Epidemiology, and End Results Program (SEER)-registered gastric cancer patients were used for analysis in this study. Patients operated on for gastric cancer at N0 stage between 2004 and 2012 were identified from the SEER database. The association between the LN counts and survival was assessed using the Cox proportional hazards model. Patients were stratified into 1-4, 5-13, and > 13 subgroups according to LN count cut-off values determined by X-tile program, with the 5-year cause specific survival (CSS) rate of 64.8%, 72.5%, and 79.4%, respectively. LN count was also validated as an independently prognostic factor in multivariate Cox analysis (P < 0.001). In addition, nomograms including LN counts on CSS were established according to all significant factors, and the c index was 0.703 (95% CI: 0.672-0.734). Further study indicated that patients with no LN metastasis had a decreased risk of death for each patient with LN examined up to approximately 14 LNs. Collectively, our study firmly demonstrated that the number of the retrieved LNs count was an independent prognostic factor for gastric cancer with no LN metastasis. The higher the LN count, the better the survival would be; the best CSS was observed on the LN count more than 14. PMID- 27270654 TI - Crosstalk between osteoprotegerin (OPG), fatty acid synthase (FASN) and, cycloxygenase-2 (COX-2) in breast cancer: implications in carcinogenesis. AB - The crosstalk between malignant and nonmalignant cells in the tumor microenvironment, as maneuvered by cytokines/chemokines, drives breast cancer progression. In our previous study, we discovered Osteoprotegerin (OPG) as one of the cytokines heavily secreted by breast cancer cells. We demonstrated that OPG is expressed and secreted at very high levels from the highly invasive breast cancer cell lines SUM149PT and SUM1315MO2 as compared to normal human mammary epithelial HMEC cells. OPG was involved in modulating aneuploidy, cell proliferation, and angiogenesis in breast cancer. Mass spectrometry analysis performed in this study revealed OPG interacts with fatty acid synthase (FASN), which is a key enzyme of the fatty acid biosynthetic pathway in breast cancer cells. Further, electron microscopy, immunofluorescence, and fluorescence quantitation assays highlighted the presence of a large number of lipid bodies (lipid droplets) in SUM149PT and SUM1315MO2 cells in comparison to HMEC. We recently showed upregulation of the COX-2 inflammatory pathway and its metabolite PGE2 secretion in SUM149PT and SUM1315MO2 breast cancer cells. Interestingly, human breast cancer tissue samples displayed high expression of OPG, PGE2 and fatty acid synthase (FASN). FASN is a multifunctional enzyme involved in lipid biosynthesis. Immunofluorescence staining revealed the co-existence of COX-2 and FASN in the lipid bodies of breast cancer cells. We reasoned that there might be crosstalk between OPG, FASN, and COX-2 that sustains the inflammatory pathways in breast cancer. Interestingly, knocking down OPG by CRISPR/Cas9 gene editing in breast cancer cells decreased FASN expression at the protein level. Here, we identified cis-acting elements involved in the transcriptional regulation of COX 2 and FASN by recombinant human OPG (rhOPG). Treatment with FASN inhibitor C75 and COX-2 inhibitor celecoxib individually decreased the number of lipid bodies/cell, downregulated phosphorylation of ERK, GSK3beta, and induced apoptosis by caspase-3/7 and caspase-9 activation. But a more efficient and effective decrease in lipid bodies/cell and survival kinase signaling was observed upon combining the drug treatments for the aggressive cancer cells. Collectively, the novel biological crosstalk between OPG, FASN, and COX-2 advocates for combinatorial drug treatment to block these players of carcinogenesis as a promising therapeutic target to treat highly invasive breast cancer. PMID- 27270658 TI - Tinnitus. PMID- 27270659 TI - Should We Treat for Subclinical Hypothyroidism?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center. AB - In May 2015, the U.S. Preventive Services Task Force issued a guideline on screening for thyroid disease that included a systematic evidence review and an update of its 2004 recommendations. The review assessed the effect of treating screen-detected subclinical thyroid dysfunction on health outcomes. It found adequate evidence that treating subclinical hypothyroidism does not provide clinically meaningful improvements in blood pressure, body mass index, bone mineral density, lipid levels, or quality-of-life measures. The review also concluded that evidence was inadequate to determine whether screening for thyroid dysfunction reduced cardiovascular disease or related morbidity and mortality. In separate guidelines, the American Association of Clinical Endocrinologists and American Thyroid Association advocated aggressive case-finding and recommended screening persons with certain clinical conditions or characteristics rather than the general population. These societies argue that subclinical hypothyroidism adversely affects cardiovascular outcomes and thus merits case-finding. Here, 2 experts discuss their perspectives on whether treating subclinical hypothyroidism reduces morbidity and mortality, whether there are harms of treatment, and how they would balance the benefits and harms of treatment both in general and for a specific patient. PMID- 27270661 TI - Breast Cancer Screening and Prevention. AB - This issue provides a clinical overview of breast cancer screening and prevention, focusing on risk assessment, screening, prevention, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers. PMID- 27270657 TI - HIF2alpha/EFEMP1 cascade mediates hypoxic effects on breast cancer stem cell hierarchy. AB - Breast cancer stem cells (BCSCs) have been shown to contribute to tumor growth, metastasis, and recurrence. They are also markedly resistant to conventional cancer treatments, such as chemotherapy and radiation. Recent studies have suggested that hypoxia is one of the prominent micro-environmental factors that increase the self-renewal ability of BCSCs, partially by enhancing CSC phenotypes. Thus, the identification and development of new therapeutic approaches based on targeting the hypoxia-dependent responses in BCSCs is urgent. Through various in vitro studies, we found that hypoxia specifically up-regulates BCSC sphere formation and a subset of CD44+/CD24-/low CSCs. Hypoxia inducible factors 2alpha (HIF2alpha) depletion suppressed CSC-like phenotypes and CSC mediated drug resistance in breast cancer. Furthermore, the stimulatory effects of hypoxia-induced HIF2alpha on BCSC sphere formation were successfully attenuated by epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) knockdown. Taken together, these data suggest that HIF2alpha mediates hypoxia-induced cancer growth/metastasis and that EFEMP1 is a downstream effector of hypoxia-induced HIF2alpha during breast tumorigenesis. PMID- 27270662 TI - Web Exclusives. Annals Graphic Medicine - A Brief Anatomy of My Anxiety: The OCD Variety. PMID- 27270663 TI - Impact Evaluation of a System-Wide Chronic Disease Management Program on Health Service Utilisation: A Propensity-Matched Cohort Study. AB - BACKGROUND: The New South Wales Health (NSW Health) Chronic Disease Management Program (CDMP) delivers interventions to adults at risk of hospitalisation for five target chronic conditions that respond well to ambulatory care: diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, and coronary artery disease. The intervention consists of two main components: (1) care coordination across sectors (acute, ambulatory, and community care from both public and private sectors) and clinical specialties, facilitated by program care coordinators, and (2) health coaching including management of lifestyle risk factors and medications and self-management. These components were broadly prescribed by the head office of NSW Health, which funded the program, and were implemented by regional health services (local health districts) in ways that best suited their own history, environment, workforce, and patient need. We used a propensity-matched cohort study to evaluate health service utilisation after enrolment in the CDMP. METHODS AND FINDINGS: The evaluation cohort included 41,303 CDMP participants enrolled between 1 January 2011 and 31 December 2013 who experienced at least one hospital admission or emergency department (ED) presentation for a target condition in the 12 mo preceding enrolment. Potential controls were selected from patients not enrolled in the CDMP but experiencing at least one hospital admission or ED presentation over the same period. Each CDMP patient in the evaluation cohort was matched to one control using 1:1 propensity score matching. The primary outcome was avoidable hospitalisations. Secondary outcomes included avoidable readmissions, avoidable bed days, unplanned hospitalisations, unplanned readmissions, unplanned bed days, ED presentations, and all-cause death. The primary analysis consisted of 30,057 CDMP participants and 30,057 matched controls with a median follow-up of 15 mo. Of those, 25,638 (85.3%) and 25,597 (85.2%) were alive by the end of follow-up in the CDMP and control groups, respectively. Baseline characteristics (including history of health service utilisation) were well balanced between the matched groups. In both groups, utilisation peaked just before the time of enrolment/matching, declined sharply immediately following enrolment, and then continued to decrease more gradually; however, after enrolment, avoidable and unplanned health service utilisation remained higher for CDMP participants compared to controls. The adjusted yearly rate of avoidable hospital admissions was 0.57 (95% CI 0.52 to 0.62) in the CDMP group versus 0.33 (95% CI 0.31 to 0.37) in the control group (adjusted rate ratio 1.70, 95% CI 1.62 to 1.79, p < 0.001). Significant increases in service utilisation were also observed for unplanned hospitalisations (1.42, 95% CI 1.37 to 1.47, p < 0.001) and ED presentations (1.37, 95% CI 1.32 to 1.42, p < 0.001) as well as avoidable (2.00, 95% CI 1.80 to 2.22, p < 0.001) and unplanned (1.51, 95% CI 1.40 to 1.62, p < 0.001) readmissions and avoidable (1.70, 95% CI 1.59 to 1.82, p < 0.001) and unplanned (1.43, 95% CI 1.36 to 1.49, p < 0.001) bed days. No evidence of a difference was seen for all-cause death (adjusted risk ratio 0.96, 95% CI 0.96 to 1.01, p = 0.10) or non-avoidable hospitalisations (all hospitalisations minus avoidable hospitalisations; adjusted rate ratio 1.03, 95% CI 0.97 to 1.10, p = 0.26). Despite the robustness of these results to sensitivity analyses, in the absence of a randomised control group, one cannot exclude the possibility of residual or unmeasured confounding that was not controlled for by the matching process and multivariable analyses. CONCLUSIONS: Participation in the CDMP was associated with an increase in avoidable hospital admissions compared to matched controls but no difference in the rate of other types of hospitalisation or death. A possible explanation is that the program identified conditions that required participants to be hospitalised. Service utilisation decreased sharply following its peak for both groups. This finding reflects the natural tendency for high-risk patients to show reductions in use following intense phases of service utilisation and highlights that, despite the additional complexity, a carefully selected control group is essential when assessing the effectiveness of interventions on hospital use. PMID- 27270664 TI - Self-Assembly of Measles Virus Nucleocapsid-like Particles: Kinetics and RNA Sequence Dependence. AB - Measles virus RNA genomes are packaged into helical nucleocapsids (NCs), comprising thousands of nucleo-proteins (N) that bind the entire genome. N-RNA provides the template for replication and transcription by the viral polymerase and is a promising target for viral inhibition. Elucidation of mechanisms regulating this process has been severely hampered by the inability to controllably assemble NCs. Here, we demonstrate self-organization of N into NC like particles in vitro upon addition of RNA, providing a simple and versatile tool for investigating assembly. Real-time NMR and fluorescence spectroscopy reveals biphasic assembly kinetics. Remarkably, assembly depends strongly on the RNA-sequence, with the genomic 5' end and poly-Adenine sequences assembling efficiently, while sequences such as poly-Uracil are incompetent for NC formation. This observation has important consequences for understanding the assembly process. PMID- 27270665 TI - Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study. AB - Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) increase atherosclerotic cardiovascular disease risk. Cholesterol efflux capacity (CEC) is a key metric of the anti-atherosclerotic functionality of high-density lipoproteins (HDL). The present study aimed to delineate if T2DM and MetS cross sectionally associate with altered CEC in a large high cardiometabolic risk population. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma from 552 subjects of the CODAM cohort (288 controls, 126 impaired glucose metabolism [IGM], 138 T2DM). MetS was present in 297 participants. CEC was not different between different glucose tolerance categories but was lower in MetS (P < 0.001), at least partly attributable to lower HDL cholesterol (HDL-C) and apoA-I levels (P < 0.001 for each). Low grade inflammation was increased in IGM, T2DM and MetS as determined by a score comprising 8 different biomarkers (P < 0.05-< 0.001; n = 547). CEC inversely associated with low-grade inflammation taking account of HDL-C or apoA-I in MetS (P < 0.02), but not in subjects without MetS (interaction: P = 0.015). This study demonstrates that IGM and T2DM do not impact the HDL CEC function, while efflux is lower in MetS, partly dependent on plasma HDL-C levels. Enhanced low-grade inflammation in MetS may conceivably impair CEC even independent of HDL-C and apoA-I. PMID- 27270666 TI - Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States. AB - Neutrophils exit the vasculature and swarm to sites of inflammation and infection. However, these cells are abundant in the healthy, inflammation-free human oral environment, suggesting a unique immune surveillance role within the periodontium. We hypothesize that neutrophils in the healthy oral cavity occur in an intermediary parainflammatory state that allows them to interact with and contain the oral microflora without eliciting a marked inflammatory response. Based on a high-throughput screen of neutrophil CD (cluster of differentiation) marker expression and a thorough literature review, we developed multicolor flow cytometry panels to determine the surface marker signatures of oral neutrophil subsets in periodontal health and disease. We define here 3 distinct neutrophil subsets: resting/naive circulatory neutrophils, parainflammatory neutrophils found in the healthy oral cavity, and proinflammatory neutrophils found in the oral cavity during chronic periodontal disease. Furthermore, parainflammatory neutrophils manifest as 2 distinct subpopulations-based on size, granularity, and expression of specific CD markers-and exhibit intermediate levels of activation as compared with the proinflammatory oral neutrophils. These intermediately activated parainflammatory populations occur in equal proportions in the healthy oral cavity, with a shift to one highly activated proinflammatory neutrophil population in chronic periodontal disease. This work is the first to identify and characterize oral parainflammatory neutrophils that interact with commensal biofilms without inducing an inflammatory response, thereby demonstrating that not all neutrophils trafficking through periodontal tissues are fully activated. In addition to establishing possible diagnostic and treatment monitoring biomarkers, this oral neutrophil phenotype model builds on existing literature suggesting that the healthy periodontium may be in a parainflammatory state. PMID- 27270667 TI - The ghost sex-life of the paedogenetic beetle Micromalthus debilis. AB - Genetic and sexual systems can be evolutionarily dynamic within and among clades. However, identifying the processes responsible for switches between, for instance, sexual and asexual reproduction, or cyclic and non-cyclic life histories remains challenging. When animals evolve parthenogenetic reproduction, information about the sexual mating system becomes lost. Here we report an extraordinary case where we have been able to resurrect sexual adults in a species of beetle that reproduces by parthenogenetic paedogenesis, without the production of adults. Via heat treatment, we were able to artificially induce adult beetles of Micromalthus debilis in order to describe its pre-paedogenetic mating system. Adults showed a highly female biased sex ratio, out-breeding behaviour, and sex-role reversal. Paedogenetic larvae of Micromalthus are infected with the endosymbiotic bacteria Rickettsia and Wolbachia. Clear signs of vestigialization in adults are concurrent with the loss of adults. Our data suggest an ancient female sex ratio bias that predates the loss of adults, perhaps associated with endosymbionts. We propose a model for the transition from a haplodiploid cyclical parthenogenetic life history to parthenogenetic paedogenesis. Paedogenetic development induces a new mechanism of sex ratio bias in midges, wasps and beetles. PMID- 27270668 TI - How did media present the radiation risks after the Fukushima accident: a content analysis of newspapers in Europe. AB - Any activity that might result in exposure of a population to contaminants requires communication of the associated risks. This communication is complicated by several factors including public perceptions, distrust, uncertainties in risk assessment and news media. These factors are especially prominent in communication of risks from ionizing radiation. A number of guidelines about the communication of risks related to radiation exposures have been made by national and international authorities and other stakeholders. The present paper investigates whether those guidelines were followed and evaluates how the radiation risk related information was presented in European newspapers and Russia in the aftermath of the Fukushima accident. It examines the use of measurement units and risk comparisons, the quality of the statements on radiation risk related issues and the use of visual materials in 1340 newspaper articles from Belgium, Italy, Norway, Russia, Slovenia and Spain. Our results indicated several misinterpretations and misrepresentations of radiological risks in the newspaper articles. We also show an inconsistency in the information that was reported with advice provided to risk communicators (e.g. authorities and experts) in the guidelines. The results suggest that risk communicators should improve their communication practices regarding radiological risks, in order to improve emergency management response. PMID- 27270669 TI - Multifunctional in vivo imaging of pancreatic islets during diabetes development. AB - Pancreatic islet dysfunction leading to insufficient glucose-stimulated insulin secretion triggers the clinical onset of diabetes. How islet dysfunction develops is not well understood at the cellular level, partly owing to the lack of approaches to study single islets longitudinally in vivo Here, we present a noninvasive, high-resolution system to quantitatively image real-time glucose metabolism from single islets in vivo, currently not available with any other method. In addition, this multifunctional system simultaneously reports islet function, proliferation, vasculature and macrophage infiltration in vivo from the same set of images. Applying our method to a longitudinal high-fat diet study revealed changes in islet function as well as alternations in islet microenvironment. More importantly, this label-free system enabled us to image real-time glucose metabolism directly from single human islets in vivo for the first time, opening the door to noninvasive longitudinal in vivo studies of healthy and diabetic human islets. PMID- 27270670 TI - Signaling pathways controlling activity-dependent local translation of BDNF and their localization in dendritic arbors. AB - Brain-derived neurotrophic factor (BDNF) is encoded by multiple mRNA variants whose differential subcellular distribution constitutes a 'spatial code' for local translation of BDNF and selective morphological remodeling of dendrites. Here, we investigated where BDNF translation takes place and what are the signaling pathways involved. Cultured hippocampal neurons treated with KCl showed increased BDNF in the soma, proximal and distal dendrites, even in quaternary branches. This activity-dependent increase of BDNF was abolished by cycloheximide, suggesting local translation, and required activation of glutamate and Trk receptors. Our data showed that BDNF translation was regulated by multiple signaling cascades including RAS-Erk and mTOR pathways, and CaMKII CPEB1, Aurora-A-CPEB1 and Src-ZBP1 pathways. Aurora-A, CPEB1, ZBP1 (also known as IGF2BP1), eiF4E, S6 (also known as rpS6) were present throughout the dendritic arbor. Neuronal activity increased the levels of Aurora-A, CPEB1 and ZBP1 in distal dendrites whereas those of eiF4E and S6 were unaffected. BDNF-6, the main dendritic BDNF transcript, was translated in the same subcellular domains and in response to the same pathways as total BDNF. In conclusion, we identified the signaling cascades controlling BDNF translation and we describe how the translational machinery localization is modulated in response to electrical activity. PMID- 27270671 TI - Driving the Way to Tuberculosis Elimination: The Essential Role of Fundamental Research. AB - Tuberculosis has impacted human health for millennia. The World Health Organization estimated that, in 2014, 9.6 million people developed tuberculosis and 1.5 million people died from the disease. In May 2014, the World Health Assembly endorsed the new "End TB Strategy" that presents a pathway to tuberculosis elimination. The strategy outlines 3 areas of emphasis, one of which is intensified research and innovation. In this article we highlight the essential role for fundamental tuberculosis research in the future of tuberculosis diagnostics, treatment, and prevention. To maximize the impact of fundamental research, we must foster collaboration among all stakeholders engaged in tuberculosis research and control to facilitate open dialogue to assure that critical gaps in outcome-oriented science are identified and addressed. We present here a framework for future discussions among scientists, physicians, research and development specialists, and public health managers for the reinforcement of national and international strategies toward tuberculosis elimination. PMID- 27270672 TI - Longer ovarian stimulation reduces embryo number and clinical pregnancy rate in long GnRH agonist cycles. AB - BACKGROUND: The aim of this study was to analyze whether the length of controlled ovarian stimulation affects in vitro fertilization (IVF) cycle outcomes. METHODS: This retrospective cohort study was performed at a private, university-affiliated fertility centre. We reviewed 1522 IVF cycles, comprising 979 long gonadotropin releasing hormone (GnRH) agonist and 543 GnRH antagonist protocols. All subjects underwent controlled ovarian stimulation followed by fresh embryo transfer. Logistic regression analysis was used to examine the relationship between trigger day and the following cycle outcomes: normal fertilization rate (FR), proportion of mature oocytes, proportion of cycles with embryos for cryopreservation, and clinical pregnancy rate (CPR). RESULTS: In long agonist cycles, having more days of stimulation was associated with a lower clinical pregnancy rate (OR=0.87, 95% CI=0.80-0.96, P=0.01). Longer stimulation also resulted in fewer cycles with supernumerary embryos for cryopreservation (OR=0.84, 95% CI=0.77-0.92, P=0.0005), despite a having greater number of mature oocytes retreived (OR=1.05, 95% CI=1.01 1.10, P=0.04). For each additional day of stimulation in a long agonist protocol, the odds of achieving a clinical pregnancy were reduced by 13% and of achieving cryopreservation by 16%. In the antagonist protocol group, the length of ovarian stimulation did not have an effect on the clinical pregnancy and cryopreservation rates. CONCLUSIONS: Longer duration of ovarian stimulation appears to reduce clinical pregnancy and embryo cryopreservation rates in subjects undergoing long GnRH agonist cycles. The number of days of stimulation does not appear to affect those using the GnRH antagonist protocol. PMID- 27270673 TI - [A message from the new Editor of the Revista de Neurologia]. PMID- 27270674 TI - [Peripheral nerve stimulation effectiveness in the upper limb function recovery of patients with a stroke sequel: systematic review and meta-analysis]. AB - INTRODUCTION: In 30-66% of the cases, people who survive a stroke suffer from an affected non functional upper limb. Somatosensory stimulation might positively influence the muscular activity of patients with motor deficiencies caused by a stroke. AIM: To carry out a systematic review and a meta-analysis of the effectiveness of peripheral nerve stimulation (PNS) use in the improvement of the plegic/paretic upper limb function in patients with a stroke sequel. SUBJECTS AND METHODS: Randomized and non randomized clinically controlled tests and crossover studies published until November 2014 in Medline electronic database, Cochrane Central Register of Controlled Trials, LILACS, SciELO and Open Grey were included. Studies at high risk of bias were excluded. Two independent researchers assessed the studies' eligibility criteria and retrieved and analyzed all data. RESULTS: A total of 1,967 studies were found, five of them were included for data retrieval and analysis, using a risk of bias fashion of 6/10 at the PEDro scale. 224 patients were included, 95 of them received PNS in multiple modalities and 129 received other interventions as a control group. CONCLUSION: The analyzed data suggest that the function of the plegic/paretic upper limb improves after the application of PNS either with or without functional training. On the other hand, the meta-analysis result indicates that there is still insufficient evidence to guarantee the effectiveness of PNS use for the recovery of the plegic/paretic upper limb function in patients with a stroke sequel. PMID- 27270675 TI - [Impact of acquired brain injury towards the community integration: employment outcome, disability and dependence two years after injury]. AB - AIMS: To analyze the impact of acquired brain injury towards the community integration (professional career, disability, and dependence) in a sample of people affected by vascular, traumatic and tumor etiology acquired brain damage, over a two year time period after the original injury, and also to examine what sociodemographic variables, premorbid and injury related clinical data can predict the level of the person's integration into the community. PATIENTS AND METHODS: 106 adults sample suffering from acquired brain injury who were attended by the Neuropsychology and Neuropsychiatry Department at Hospital of Navarra (Spain) affected by memory deficit as their main sequel. Differences among groups have been analyzed by using t by Student, chi squared and U by Mann-Whitney tests. RESULTS: 19% and 29% of the participants who were actively working before the injury got back their previous status within one and two years time respectively. 45% of the total sample were recognized disabled and 17% dependant. No relationship between sociodemographic and clinical variables and functional parameters observed were found. CONCLUSIONS: Acquired brain damage presents a high intensity impact on affected person's life trajectory. Nevertheless, in Spain, its consequences at sociolaboral adjustment over the the two years following the damage through functional parameters analyzed with official governmental means over a vascular, traumatic and tumor etiology sample had never been studied before. PMID- 27270676 TI - [Study of the diagnostic agreement on headaches between neurology and primary care]. AB - INTRODUCTION: Headache as a symptom is a very common disease and one of the main reasons for consultation in primary care. AIM: To analyze the characteristics of patients referred from primary care to general neurology whose chief complaint was headache and/or neuralgia and diagnostic agreement. PATIENTS AND METHODS: Cross-sectional study of all patients referred from primary care; demographic/clinical variables were collected and diagnostic hypothesis by primary care and general neurology were compared by determining their agreement. RESULTS: 2,514 were referred from primary care patients (588 of them on a preferential basis); in 378 cases the reason for consultation was headache and/or neuralgia (average 42.46 years; 77.8% female). In 139 patients it was established only a semiological diagnostic and other episodic migraine predominated (49.79%), chronic tension headache (18.41%) and trigeminal neuralgia (12.13%). Since general neurology, the most common diagnoses were, respectively, 33.86%, 24.05% and 18.67%. A compatible kappa coefficient of 0.543 (p < 0.05) with a moderate agreement when considering only those patients referred from primary care to a specific diagnosis was obtained. CONCLUSIONS: Headaches are a very common reason for consultation in primary care (15%). The diagnostic agreement is moderate in our health sector so it is necessary to design training programs to help outline the criteria for referral to specialists and improve care for our patients. PMID- 27270677 TI - [Bilateral cerebellopontine arachnoid cyst]. AB - INTRODUCTION: Bilateral cerebellopontine arachnoid cysts are very rare, and only three cases have been previously reported. CASE REPORT: A 14-year-old previously healthy girl presented to our outpatient clinic with a 6-weeks history of frontal headache. They typically would start in the occipital region and then radiate bifrontally. The neurological examination was unremarkable. Magnetic resonance imaging revealed an extra-axial bilateral lesion in bilateral cerebellopontine angle, larger on left side. The lesions were homogeneously hypointenese on T1 weighted imaging and hyperintense on T2-weighted imaging without evidence of contrast enhancement and without evidence of restriction on diffusion-weighted imaging. No surgical treatment was indicated. CONCLUSIONS: Bilateral arachnoid cysts of the cerebellopontine angle are very infrequent and the main indication for surgery is the existence of clinical symptoms or neurological deficit coincident with the locations of the cysts. PMID- 27270679 TI - [Halo sign in the facial artery. An aid in the diagnosis of giant-cell arteritis]. PMID- 27270678 TI - Review of the novelties from the 31st ECTRIMS Congress, 2015, presented at the 8th Post-ECTRIMS meeting. AB - Renowned national specialists in multiple sclerosis (MS) met, for the eighth year in a row, to give details of the latest novelties presented at the last ECTRIMS Congress 2015, which are included in this review. One of the highlights at this Congress was the new classification of the phenotypes of MS. Both the diagnostic criteria of the neuromyelitis optica spectrum and the problems involved in the differential diagnosis derived from the lack of definition of the radiological spectrum were reviewed. The microbiota comes to the fore as a possible factor determining the disease, together with extrinsic factors such as tobacco, salt ingestion or vitamin D deficiency. Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica. Certain antibiotics and vitamins could also play a role in the treatment of MS. In this edition of the Congress special attention was paid to personalised therapy. To date, 11 drugs have been approved for use in Europe. There is a need for therapeutic algorithms that help us to choose the best treatment for each patient. Likewise, we need to be able to identify, in the early stages of the disease, the risk of developing disability, so as to be able to design therapeutic strategies. To do so, molecular biomarkers and other predictive tools are required. The problems that still exist in software technology in magnetic resonance hinder its application in daily clinical practice. PMID- 27270680 TI - [Infection by the hepatitis E virus as a precipitating factor of Parsonage-Turner syndrome]. PMID- 27270681 TI - [Spanish neuroscience in times of Don Quixote]. PMID- 27270682 TI - [Spanish neuroscience in times of Don Quixote]. PMID- 27270683 TI - Making one-sided exercise decisions: The influence of exercise-related cognitive errors. AB - Exercise-related cognitive errors reflect biased processing of exercise-relevant information. The purpose of this study was to examine whether differences existed between individuals reporting low and high exercise-related cognitive errors on information processed about a relevant exercise decision-making situation. In all, 138 adults completed an online questionnaire. The high exercise-related cognitive error group primarily focused on negative content about the situation compared to the low exercise-related cognitive error group who focused on both positive and negative content. The high exercise-related cognitive error group displayed biased processing of exercise information, as suggested by the cognitive errors model. Future research should examine whether biasing information processing caused by exercise-related cognitive errors can be modified and attenuated. PMID- 27270684 TI - How do women with secondary breast cancer experience telling their adolescent children about their diagnosis? AB - This study investigated how women with secondary breast cancer experience telling their adolescent children. Semi-structured interviews were conducted with women who had been diagnosed with secondary breast cancer at least 1 year prior to the interview. Seven women, who had at least one child between 12 and 19 years old living at home at the time of diagnosis, were interviewed. The interviews were analysed using interpretative phenomenological analysis for an in-depth understanding of women's experiences. Women found that it was easier to tell their children of their secondary breast cancer diagnosis compared to their primary cancer. However, they talked about the impact the diagnosis had on their family. PMID- 27270685 TI - Distinct characteristics of asymmetric magnetic reconnections: Observational results from the exhaust region at the dayside magnetopause. AB - Magnetic reconnection plays a key role in the conversion of magnetic energy into the thermal and kinetic energy of plasma. On either side of the diffusion region in space plasma, the conditions for the occurrence of reconnections are usually not symmetric. Previous theoretical studies have predicted that reconnections under asymmetric conditions will bear different features compared with those of symmetric reconnections, and numerical simulations have verified these distinct features. However, to date, the features of asymmetric reconnections have not been thoroughly investigated using in situ observations; thus, some results from theoretical studies and simulations have not been tested with observations sufficiently well. Here, spacecraft observations are used in a statistical investigation of asymmetric magnetic reconnection exhaust at the dayside magnetopause. The resulting observational features are consistent with the theoretical predictions. The results presented here advance our understanding of the development of reconnections under asymmetric conditions. PMID- 27270686 TI - Biomarkers: stepping stones to firmer end points. PMID- 27270688 TI - Rate dependent of strength in metallic glasses at different temperatures. AB - The correlation between the strength at the macroscale and the elastic deformation as well as shear cracking behavior at the microscale of bulk metallic glasses (BMGs) is investigated. The temperatures of 298 K and 77 K as well as the strain rate ranging from 10(-6) s(-1) to 10(-2) s(-1) are applied to the BMGs, in which the mechanical responses of the BMGs are profiled through the compression tests. The yield strength is associated with the activation of the elementary deformation unit, which is insensitive to the strain rate. The maximum compressive strength is linked to the crack propagation during shear fracture process, which is influenced by the strain rate. The cryogenic temperature of 77 K significantly improves the yield strength and the maximum compressive strength of the BMGs. PMID- 27270687 TI - Does advancing male age influence the expression levels and localisation patterns of phospholipase C zeta (PLCzeta) in human sperm? AB - Socio-economic factors have led to an increasing trend for couples to delay parenthood. However, advancing age exerts detrimental effects upon gametes which can have serious consequences upon embryo viability. While such effects are well documented for the oocyte, relatively little is known with regard to the sperm. One fundamental role of sperm is to activate the oocyte at fertilisation, a process initiated by phospholipase C zeta (PLCzeta), a sperm-specific protein. While PLCzeta deficiency can lead to oocyte activation deficiency and infertility, it is currently unknown whether the expression or function of PLCzeta is compromised by advancing male age. Here, we evaluate sperm motility and the proportion of sperm expressing PLCzeta in 71 males (22-54 years; 44 fertile controls and 27 infertile patients), along with total levels and localisation patterns of PLCzeta within the sperm head. Three different statistical approaches were deployed with male age considered both as a categorical and a continuous factor. While progressive motility was negatively correlated with male age, all three statistical models concurred that no PLCzeta related parameter was associated with male age, suggesting that advancing male age is unlikely to cause problems in terms of the sperm's fundamental ability to activate an oocyte. PMID- 27270689 TI - Relief of Protracted Catatonic Symptoms with Prolonged Electroconvulsive Therapy. PMID- 27270690 TI - Effective Removal of kappa-Free Light Chains with Hemodialysis Using Fresenius Ultraflux(r) EMiC(r)2 Dialyser in a Patient with Myeloma Cast Nephropathy, with Associated Cost Savings. PMID- 27270691 TI - What women want: social characteristics, gender-based violence and social support preferences in a cohort of women living with HIV. AB - A total of 229 women attend Chalmers Centre (a city-centre integrated sexual health centre in Edinburgh, Scotland) for their HIV care and treatment. Local third-sector agencies provide peer support, but anecdotally, it is not well utilised and some demographic groups are under-represented. The aim of this study was to gain better understanding of the background social characteristics of these women, to ascertain what issues they are affected by, and to better identify what support is required and how it should be provided/facilitated. An anonymous self-completion questionnaire was developed, and all women attending HIV clinics between July and November 2015 were given the opportunity to participate. Additional data were accessed from the National Sexual Health database on cohort size and gender-based violence enquiries. Forty-four women living with HIV completed the questionnaire. 25% are unemployed. 84.6% had a combined household income of less than L30,000 per annum. 16.7% do not know anyone else, and 59.5% know only one other person, who is living with HIV. 32.6% would like to meet other/more women living with HIV, and 25.5% were unsure if they did or not. Of those who would, 42.9% would prefer a one-to-one setting, 42.9% would prefer a group setting, and 14.3% did not mind. 64.3% would prefer to meet off NHS premises. 26.8% were interested in discussion groups on women's issues, and 31.7% were unsure. The most popular suggestions for discussion group topics were stress/anxiety (nine women), HIV disclosure (eight women), diet and nutrition (seven women), and pregnancy and childbirth (six women). 26.8% were interested in attending a "women clinic" staffed by female staff, the same number were unsure if they would utilise this service or not. 50% of women had, at some point, experienced gender-based violence, 13.5% were currently experiencing gender-based violence, and four of these women have children living with them. From National Sexual Health records, only 15.7% of the cohort had ever been asked about gender-based violence. Respondents were demographically representative of our whole cohort. 75% are in employment but it appears that the majority of these women are likely to be earning lower than the national average income. To improve holistic support for these women and facilitate peer support, we need to be flexible in our approach. Gender-based violence appears to be disproportionately affecting women living with HIV in Lothian and, as a team, we are failing to routinely enquire about it. Robust referral/signposting pathways should be developed for women after gender-based violence disclosure. PMID- 27270692 TI - Acute onset myopericarditis as unusual presentation of primary HIV infection. AB - A 30-year-old man was admitted to hospital after complaining of a retrosternal burning pain, radiating to the jugular region, and to both upper limbs. An electrocardiography examination showed a ST segment elevation involving the lower lateral leads. A trans-thoracic ultrasonography showed findings compatible with an acute myopericarditis. All performed serological testings excluded other recent infections with cardiac tropism. Among screening tests, a peripheral lymphocyte subset analysis was performed and an inversion of the CD4/CD8 ratio was found. Therefore, HIV testing was performed and proved positive for HIV-1 antibodies. The discovery of a primary HIV infection with involvement of a vital organ led us to start HAART. On day 20, our patient underwent a right heart catheterization and endomyocardial biopsy. During the following days, the clinical conditions of our patient improved, and a further heart ultrasonography documented a mild pericardial thickening as a result of the recent myopericarditis. Also the evolving changes of ECG were compatible with a benign evolution of myopericarditis. The histopathologic studies revealed a mild fibrosis of the myocardial right ventricular tissue, and inflammatory findings compatible with a recent myocarditis. At the real-time PCR analysis on bioptic sample, only HHV6 DNA and HIV-DNA were reactive. An immunofluorescence staining was performed to highlight the HIV p24 protein and a positive signal was detected in myocardial tissue. Considering the low avidity level of the anti-HIV IgG antibodies and the positivity of HIV-DNA in the endomyocardial tissue, we believe that the clinical manifestation presented can be referred to the recent primary HIV-infection. PMID- 27270693 TI - Joshua Lederberg on Bacterial Recombination. PMID- 27270694 TI - Curt Stern on Somatic Crossing Over. PMID- 27270695 TI - Massively Parallel Genetics. AB - Human genetics has historically depended on the identification of individuals whose natural genetic variation underlies an observable trait or disease risk. Here we argue that new technologies now augment this historical approach by allowing the use of massively parallel assays in model systems to measure the functional effects of genetic variation in many human genes. These studies will help establish the disease risk of both observed and potential genetic variants and to overcome the problem of "variants of uncertain significance." PMID- 27270696 TI - A Brief History of Schizosaccharomyces pombe Research: A Perspective Over the Past 70 Years. AB - Since its humble start as a model organism in two European laboratories in the 1940s and 1950s, the fission yeast Schizosaccharomyces pombe has grown to become one of the best-studied eukaryotes today. This article outlines the way in which interest in S. pombe developed and spread from Europe to Japan, North America, and elsewhere from its beginnings up to the first International Meeting devoted to this yeast in 1999. We describe the expansion of S. pombe research during this period with an emphasis on many of the individual researchers involved and their interactions that resulted in the development of today's vibrant community. PMID- 27270697 TI - Learning and Doing: An Interview with Bill Wood. AB - THE Genetics Society of America's Elizabeth W. Jones Award for Excellence in Education recognizes significant and sustained impact on genetics education. As well as having made major contributions to biochemistry and developmental genetics, the 2016 awardee William B. Wood has been a pioneer in the reform of science teaching. Wood's leadership has been crucial in several national initiatives and programs, including the development of the influential National Academies Summer institutes on Undergraduate Education in Biology. He has also catalyzed change in education through his service as Editor-in-Chief of CBE-Life Sciences Education, a peer-reviewed journal published by the American Society for Cell Biology, in editorial partnership with the GSA. PMID- 27270700 TI - Corrigendum. PMID- 27270701 TI - Corrigendum. PMID- 27270698 TI - Tools for Predicting the Functional Impact of Nonsynonymous Genetic Variation. AB - As personal genome sequencing becomes a reality, understanding the effects of genetic variants on phenotype-particularly the impact of germline variants on disease risk and the impact of somatic variants on cancer development and treatment-continues to increase in importance. Because of their clear potential for affecting phenotype, nonsynonymous genetic variants (variants that cause a change in the amino acid sequence of a protein encoded by a gene) have long been the target of efforts to predict the effects of genetic variation. Whole-genome sequencing is identifying large numbers of nonsynonymous variants in each genome, intensifying the need for computational methods that accurately predict which of these are likely to impact disease phenotypes. This review focuses on nonsynonymous variant prediction with two aims in mind: (1) to review the prioritization methods that have been developed to date and the principles on which they are based and (2) to discuss the challenges to further improving these methods. PMID- 27270703 TI - Erratum: Correspondence: Enhancing a phase measurement by sequentially probing a solid-state system. PMID- 27270704 TI - The quest for the holy volume therapy. PMID- 27270705 TI - Confinement of water droplets on rectangular micro/nano-arrayed surfaces. AB - Micro-patterned surfaces with alternate hydrophilic and hydrophobic rectangular areas effectively confine water droplets down to attolitre volumes. The contact angle, volume, and geometry of the confined droplets as a function of the geometry and physico-chemical properties of the confining surfaces have been determined by phenomenological simulations, validated by atomic force microscopy measurements. The combination between experiments and simulations can be used for the purposeful design of arrays with surface-addressable hydrophobicity employed in digital microfluidics and high-throughput screening nanoarrays. PMID- 27270699 TI - Tetrahymena as a Unicellular Model Eukaryote: Genetic and Genomic Tools. AB - Tetrahymena thermophila is a ciliate model organism whose study has led to important discoveries and insights into both conserved and divergent biological processes. In this review, we describe the tools for the use of Tetrahymena as a model eukaryote, including an overview of its life cycle, orientation to its evolutionary roots, and methodological approaches to forward and reverse genetics. Recent genomic tools have expanded Tetrahymena's utility as a genetic model system. With the unique advantages that Tetrahymena provide, we argue that it will continue to be a model organism of choice. PMID- 27270706 TI - Exercise training comprising of single 20-s cycle sprints does not provide a sufficient stimulus for improving maximal aerobic capacity in sedentary individuals. AB - PURPOSE: Sprint interval training (SIT) provides a potent stimulus for improving maximal aerobic capacity ([Formula: see text]), which is among the strongest markers for future cardiovascular health and premature mortality. Cycling-based SIT protocols involving six or more 'all-out' 30-s Wingate sprints per training session improve [Formula: see text], but we have recently demonstrated that similar improvements in [Formula: see text] can be achieved with as few as two 20 s sprints. This suggests that the volume of sprint exercise has limited influence on subsequent training adaptations. Therefore, the aim of the present study was to examine whether a single 20-s cycle sprint per training session can provide a sufficient stimulus for improving [Formula: see text]. METHODS: Thirty sedentary or recreationally active participants (10 men/20 women; mean +/- SD age: 24 +/- 6 years, BMI: 22.6 +/- 4.0 kg m(-2), [Formula: see text]: 33 +/- 7 mL kg(-1) min( 1)) were randomised to a training group or a no-intervention control group. Training involved three exercise sessions per week for 4 weeks, consisting of a single 20-s Wingate sprint (no warm-up or cool-down). [Formula: see text] was determined prior to training and 3 days following the final training session. RESULTS: Mean [Formula: see text] did not significantly change in the training group (2.15 +/- 0.62 vs. 2.22 +/- 0.64 L min(-1)) or the control group (2.07 +/- 0.69 vs. 2.08 +/- 0.68 L min(-1); effect of time: P = 0.17; group * time interaction effect: P = 0.26). CONCLUSION: Although we have previously demonstrated that regularly performing two repeated 20-s 'all-out' cycle sprints provides a sufficient training stimulus for a robust increase in [Formula: see text], our present study suggests that this is not the case when training sessions are limited to a single sprint. PMID- 27270707 TI - Metal free TBHP-promoted intramolecular carbonylation of arenes via radical cross dehydrogenative coupling: synthesis of indenoquinolinones, 4-azafluorenones and fluorenones. AB - A metal-free, TBHP-promoted economical route is developed via the sp(2) C-H bond functionalization strategy for the synthesis of indenoquinolinones, 4 azafluorenones and fluorenones. Reactions provided excellent yield of the products under mild conditions. We have successfully synthesized 11H-indeno[1,2 b]quinolin-11-one, an antibacterial agent, in excellent yields. PMID- 27270708 TI - Cytochrome c peroxidase activity of heme bound amyloid beta peptides. AB - Heme bound amyloid beta (Abeta) peptides, which have been associated with Alzheimer's disease (AD), can catalytically oxidize ferrocytochrome c (Cyt c(II)) in the presence of hydrogen peroxide (H2O2). The rate of catalytic oxidation of Cyt(II) c has been found to be dependent on several factors, such as concentration of heme(III)-Abeta, Cyt(II) c, H2O2, pH, ionic strength of the solution, and peptide chain length of Abeta. The above features resemble the naturally occurring enzyme cytochrome c peroxidase (CCP) which is known to catalytically oxidize Cyt(II) c in the presence of H2O2. In the absence of heme(III)-Abeta, the oxidation of Cyt(II) c is not catalytic. Thus, heme-Abeta complex behaves as CCP. PMID- 27270710 TI - Rapidly Progressing Primary Extrahepatic Bile Duct Signet-Ring Cell Carcinoma in a Caucasian Woman. PMID- 27270709 TI - De novo malignancy after lung transplantation in Japan. AB - OBJECTIVE: Lung transplant recipients have an increased de novo cancer risk due to long-term immunosuppression and several oncogenic viral infections. In Japan, to date, there have been no national surveys of the incidence of de novo malignancy after lung transplantation. METHODS: This national survey was conducted by the Japanese Society for Transplantation. The questionnaire was distributed to lung transplant institutions, asking about several clinical factors related to de novo malignancy patients transplanted from 2001 to 2010. RESULTS: 179 cases of lung transplantation were performed by seven institutions in Japan between 2001 and 2010. De novo malignancies occurred in 18 patients (10.1 %). The most common malignancy was a lymphoproliferative malignancy (12 cases, including 1 double de novo cancer after tongue cancer), followed by cervical cancer (4 cases), breast cancer (2 cases), and tongue cancer (1 case). The mean time of occurrence after transplantation was 37.8 (range 4-148) months. Reduction and/or withdrawal of immunosuppression for the treatment of malignancy was seen in 14 cases. Death due to cancer occurred in 6 cases. The overall 5-year survival of 18 patients was 58.9 %. The 5-year survival of post-transplant lymphoproliferative disorder was not significantly different from that of other malignancies (47.6 and 62.5 %, respectively; p = 0.33). CONCLUSIONS: This is the first national survey of the incidence of de novo malignancy after lung transplantation in Japan. The incidence was 10.1 % and post-transplant lymphoproliferative disorder was the most common malignancy. PMID- 27270711 TI - New Approaches in Locoregional Therapies for Hepatocellular Carcinoma. AB - PURPOSE: Hepatocellular carcinoma (HCC) represent actually the fifth most common cancer worldwide, with liver transplantation and hepatic resection who represent the standard of care of curative treatment. Unfortunately, not all patient could benefit of curative treatment. For such patients, locoregional or systemic therapies represent a valid option in order to achieve the best survival possible. METHODS: A review of most interesting paper actually present in literature on locoregional treatment for nonresectable nontransplantable HCC was performed. RESULTS: A detailed description on each different approach has been detailed in each chapter. CONCLUSION: In case of nontransplantable and nonresectable HCC, locoregional treatment represent a valid alternative in management of this patients. PMID- 27270712 TI - A Review on Dietary and Non-Dietary Risk Factors Associated with Gastrointestinal Cancer. AB - INTRODUCTION: Cancer is a complex disease involving neoplasm of abnormal cells leading to development of tumor cells. Gene mutations result in aberrant gene expression, which is the major cause observed in all the cancers. The GLOBOCAN 2012 reported the highest age-standardized rates for cancer of the colorectum followed by stomach, liver, and esophagus, which are gastrointestinal cancers, and the new cases also followed the same order across the globe. Various risk factors are associated with different types of cancer which can be classified as dietary and non-dietary risk factors. The dietary risk factors include diet, alcohol, and nutrient deficiencies, whereas the non-dietary risk factors of cancers are tobacco, lifestyle choices, certain infections, occupational exposures, and environmental factors. PURPOSE: The aim of this review is to focus on the dietary and non-dietary risk factors linked to gastrointestinal cancers, which could be beneficial in clinical decision-making. PMID- 27270713 TI - HITSZ_CDR: an end-to-end chemical and disease relation extraction system for BioCreative V. AB - In this article, an end-to-end system was proposed for the challenge task of disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction in BioCreative V, where DNER includes disease mention recognition (DMR) and normalization (DN). Evaluation on the challenge corpus showed that our system achieved the highest F1-scores 86.93% on DMR, 84.11% on DN, 43.04% on CID relation extraction, respectively. The F1-score on DMR is higher than our previous one reported by the challenge organizers (86.76%), the highest F1-score of the challenge.Database URL: http://database.oxfordjournals.org/content/2016/baw077. PMID- 27270714 TI - ANItools web: a web tool for fast genome comparison within multiple bacterial strains. AB - BACKGROUND: Early classification of prokaryotes was based solely on phenotypic similarities, but modern prokaryote characterization has been strongly influenced by advances in genetic methods. With the fast development of the sequencing technology, the ever increasing number of genomic sequences per species offers the possibility for developing distance determinations based on whole-genome information. The average nucleotide identity (ANI), calculated from pair-wise comparisons of all sequences shared between two given strains, has been proposed as the new metrics for bacterial species definition and classification. RESULTS: In this study, we developed the web version of ANItools (http://ani.mypathogen.cn/), which helps users directly get ANI values from online sources. A database covering ANI values of any two strains in a genus was also included (2773 strains, 1487 species and 668 genera). Importantly, ANItools web can automatically run genome comparison between the input genomic sequence and data sequences (Genus and Species levels), and generate a graphical report for ANI calculation results. CONCLUSION: ANItools web is useful for defining the relationship between bacterial strains, further contributing to the classification and identification of bacterial species using genome data.Database URL: http://ani.mypathogen.cn/. PMID- 27270715 TI - Gene regulation knowledge commons: community action takes care of DNA binding transcription factors. AB - A large gap remains between the amount of knowledge in scientific literature and the fraction that gets curated into standardized databases, despite many curation initiatives. Yet the availability of comprehensive knowledge in databases is crucial for exploiting existing background knowledge, both for designing follow up experiments and for interpreting new experimental data. Structured resources also underpin the computational integration and modeling of regulatory pathways, which further aids our understanding of regulatory dynamics. We argue how cooperation between the scientific community and professional curators can increase the capacity of capturing precise knowledge from literature. We demonstrate this with a project in which we mobilize biological domain experts who curate large amounts of DNA binding transcription factors, and show that they, although new to the field of curation, can make valuable contributions by harvesting reported knowledge from scientific papers. Such community curation can enhance the scientific epistemic process.Database URL: http://www.tfcheckpoint.org. PMID- 27270717 TI - [The new second opinion process]. PMID- 27270716 TI - [A rare case of conductive hearing loss : Isolated fracture of the manubrium mallei as a consequence of digital manipulation in the external auditory meatus]. AB - Isolated fracture of the handle of the malleus is a rare cause of conductive hearing loss and represents a challenge for the otolaryngologist in terms of past medical history, diagnostics, and therapy. PMID- 27270718 TI - Erratum to: Transfersomal Nanoparticles for Enhanced Transdermal Delivery of Clindamycin. PMID- 27270719 TI - Erratum to: Superselective intraarterial cerebral infusion of cetuximab after osmotic blood/brain barrier disruption for recurrent malignant glioma: phase I study. PMID- 27270721 TI - Neonatal extracorporeal renal replacement therapy-a routine renal support modality? AB - Peritoneal dialysis (PD) is generally considered the preferred extracorporeal therapy for neonates with acute kidney injury (AKI). However, there are situations when PD is not suitable, such as in patients with previous abdominal surgery, hyperammonemia and significant ascites or anasarca. Additionally, with a need to start PD soon after catheter placement, there is increased risk of PD catheter leak and infection. Extracorporeal continuous renal replacement therapy (CRRT) is challenging in severely ill neonates as it requires obtaining adequately sized central venous access to accommodate adequate blood flow rates and also adaptation of a CRRT machine meant for older children and adults. In addition, ultrafiltration often cannot be set in sufficiently small increments to be suitable for neonates. Although CRRT practices can be modified to fit the needs of infants and neonates, there is a need for a device designed specifically for this population. Until that becomes available, providing the highest level of care for neonates with AKI is dependent on the shared experiences of members of the pediatric nephrology community. PMID- 27270720 TI - Perspectives on Dual Targeting Delivery Systems for Brain Tumors. AB - Brain tumor remains one of the most serious threats to human beings. Different from peripheral tumors, drug delivery to brain tumor is largely restricted by the blood brain barrier (BBB). To fully conquer this barrier and specifically deliver drugs to brain tumor, dual targeting delivery systems were explored, which are functionalized with two active targeting ligands: one to the BBB and the other to the brain tumor. The development of dual targeting delivery system is still in its early stage, and attentions need to be paid to issues and concerns that remain unresolved in future studies. PMID- 27270722 TI - Desensitization protocols for prospective pediatric renal transplant recipients. AB - Desensitization protocols should be considered for children with positive crossmatches awaiting renal transplantation. Children are sensitized usually due to previous renal (and/or other solid-organ) transplants but can be from administration of blood and/or platelet transfusions, infections, and immunizations (as sensitization from pregnancy is a rare occurrence in pediatric patients). However, the definition of HLA-incompatible (HLAi) renal transplantation in the literature varies and is best considered only when there is a positive cross-match (positive baseline flow cytometric cross-match or positive complement-dependent cytotoxic cross-match). Renal transplantation where the recipient has donor-specific antibodies (DSA) but a negative cross-match should not fall into this category, although they are higher risk. PMID- 27270723 TI - Knowledge, Perceptions and Attitudes toward Chronic Pain and Its Management: A Cross-Sectional Survey of Frontline Pharmacists in Ontario, Canada. AB - The treatment of chronic pain consumes a significant share of primary care. Community and family health team pharmacists frequently see patients with chronic pain, thus have the opportunity to improve their care. To assess the knowledge, perceptions, and attitudes of Ontario pharmacists, we invited 5,324 Ontario pharmacists, to participate in an online survey we developed using Qualtrics. The 31-question survey gathered demographic information, assessed pharmacists' knowledge of three chronic pain conditions; chronic lower back pain (CLBP, eight true/false statements); chronic headache disorder (CHD, eight true/false statements) and painful diabetic neuropathy (PDN, seven true/false statements), and their attitudes toward and perceptions of patients with these conditions, and knowledge, attitudes, and perceptions of opioids in pain management. We received 688 responses (12.9%) and 392 pharmacists completed the survey. The mean age of respondents was 48.5 years and 48.5% were male. More than 50% of respondents were in practice for more than 20 years and 58.7% worked 25-40 hours per week. The mean knowledge scores were 4.5/8, 5.5/8, and 5.3/8 for CBLP, CHD, and PDN respectively. While 95% of respondents were aware of the increasing death rates due to opioid use, only half were familiar with the Canadian guideline for safe opioid prescribing for non-cancer use. Responses were compared based on gender, time in practice and location of practice. Pharmacists with more than ten years of experience scored significantly higher than those with less experience. Fewer differences were found in comparisons of gender and location of practice. Safe and effective care of chronic pain patients, particularly with opioids, will require additional pharmacist education. PMID- 27270724 TI - Impact of tumor location on lymph node metastasis in T1 colorectal cancer. AB - PURPOSE: Data evaluating the risk of lymph node metastasis depending upon the location of the primary tumor are limited in patients with T1 colorectal cancer. We aimed to evaluate the impact of tumor location on lymph node metastasis in T1 colorectal cancer. METHODS: Patients who underwent an oncologic resection with curative intent for T1 adenocarcinoma of the colon and rectum between January 1997 and October 2014 were assessed. Exclusion criteria were distant organ metastases, previous or concurrent cancer, past history of surgical or medical cancer treatment, preoperative chemoradiation, and patients with inflammatory bowel disease or polyposis syndromes. RESULTS: Out of 232 (56 % male) patients fulfilling the study criteria, 24 (10 %) had lymph node metastasis. Age (65 vs 61 years, p = 0.1), gender (55 vs 63 % male, p = 0.5), tumor size (2 vs 2 cm, p = 0.49), and lymphovascular invasion (5 vs 8 %, p = 0.46) were not associated with lymph node metastasis. While there was no statistical significance (p = 0.2), lymph node positivity was higher in rectal cancer (14 %, n = 11/79) compared to colon cancer (9 %, n = 13/153). CONCLUSIONS: Although it was not statistically significant, lymph node positivity varies based on tumor location of T1 colorectal adenocarcinoma regardless of fundamental tumor characteristics including size, differentiation, and lymphovascular invasion. PMID- 27270725 TI - The Influence of Smoking on Pulmonary Tuberculosis in Diabetic and Non-Diabetic Patients. AB - BACKGROUND: Both smoking and diabetes can increase the risk and influence the manifestations and outcomes of tuberculosis (TB). It is not clear whether the influence of smoking on pulmonary TB differs between non-diabetic and diabetic patients. Herein, we assessed the manifestations and outcomes of TB in relation to smoking in both diabetic and non-diabetic TB patients. METHODOLOGY/PRINCIPAL FINDINGS: All diabetic culture-positive pulmonary TB patients notified from 2005 2010 at three teaching hospitals in Taiwan were enrolled. A culture-positive pulmonary TB patient without DM who was notified to the health authority immediately prior to each diabetic TB patient was selected for comparison. The 972 patients in this study cohort included 365 (37.6%) non-diabetic non-smokers, 149 (15.3%) non-diabetic smokers, 284 (29.2%) diabetic non-smokers, and 174 (17.9%) diabetic smokers. The adjusted relative risk of a pretreatment positive smear for a smoker compared with a non-smoker was 2.19 (95% CI 1.38-3.47) in non diabetic patients and 2.23 (95% CI 1.29-3.87) in diabetic culture-positive pulmonary TB patients. The adjusted relative risk for a positive smear among diabetic smokers was 5.61 (95% CI 3.35-9.41) compared with non-diabetic non smokers. Smoking was significantly associated with an increased frequency of bilateral lung parenchyma involvement (AdjOR 1.84, 95% CI 1.16-2.93), far advanced pulmonary TB (AdjOR 1.91, 95% CI 1.04-3.50), cavitary lesions (AdjOR 2.03, 95% CI 1.29-3.20), and unfavorable outcomes of TB (AdjOR 2.35, 95% CI 1.02 5.41) in non-diabetic patients. However, smoking was not associated with cavitary lung parenchyma lesions regarding the location, number or size of the cavity in diabetic TB patients. CONCLUSIONS/SIGNIFICANCE: Smoking and diabetes have joint effects on a pretreatment positive smear. Diabetic smokers had more than a 5-fold increased risk of a pretreatment positive smear than did non-diabetic non smokers, indicating remarkable joint effects of diabetes and smoking on the risk of TB transmission. PMID- 27270727 TI - Correction: Transgenerational Epigenetic Contributions to Stress Responses: Fact or Fiction? AB - [This corrects the article DOI: 10.1371/journal.pbio.1002426.]. PMID- 27270728 TI - Erratum to: Reach and representativeness of ethnic minority women in the Health Is Power Study: a longitudinal analysis. PMID- 27270726 TI - Ion Flux in Roots of Chinese Fir (Cunninghamia lanceolata (Lamb.) Hook) under Aluminum Stress. AB - Chinese fir is a tall, fast-growing species that is unique to southern China. In Chinese fir plantations, successive plantings have led to a decline in soil fertility, and aluminum toxicity is thought to be one of the main reasons for this decline. In this study, Non-invasive Micro-test Technology was used to study the effect of aluminum stress on the absorption of 4 different ions in the roots of the Chinese fir clone FS01. The results are as follows: with increased aluminum concentration and longer periods of aluminum stress, the H+ ion flow gradually changed from influx into efflux; there was a large variation in the K+ efflux, which gradually decreased with increasing duration of aluminum stress; and 1 h of aluminum stress uniformly resulted in Ca2+ influx, but it changed from influx to efflux after a longer period of aluminum stress. Changes in the different concentrations of aluminum had the largest influence on Mg2+. PMID- 27270729 TI - Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study. AB - The aim of this study is to assess the long-term safety of allogeneic umbilical cord mesenchymal stem cells (UC MSCs) transplantation for patients with refractory systemic lupus erythematosus (SLE). Nine SLE patients, who were refractory to steroid and immunosuppressive drugs treatment and underwent MSCs transplantation in 2009, were enrolled. One million allogeneic UC MSCs per kilogram of body weight were infused intravenously at days 0 and 7. The possible adverse events, including immediately after MSCs infusions, as well as the long term safety profiles were observed. Blood and urine routine test, liver function, electrocardiogram, chest radiography and serum levels of tumor markers, including alpha fetal protein (AFP), cancer embryo antigen (CEA), carbohydrate antigen 155 (CA155) and CA199, were assayed before and 1, 2, 4 and 6 years after MSCs transplantation. All the patients completed two times of MSCs infusions. One patient had mild dizzy and warm sensation 5 min after MSCs infusion, and the symptoms disappeared quickly. No other adverse event, including fluster, headache, nausea or vomit, was observed. There was no change in peripheral white blood cell count, red blood cell count and platelet number in these patients after followed up for 6 years. Liver functional analysis showed that serum alanine aminotransferase, glutamic-oxalacetic transaminase, total bilirubin and direct bilirubin remained in normal range after MSCs infusions. No newly onset abnormality was detected on electrocardiogram and chest radiography. Moreover, we found no rise of serum tumor markers, including AFP, CEA, CA125 and CA199, before and 6 years after MSCs infusions. Our long-term observational study demonstrated a good safety profile of allogeneic UC MSCs in SLE patients. PMID- 27270730 TI - Low, but Not High, Doses of Cisplatin Damage Cochlear Hair Cells in C57 Mouse Organotypic Cultures. AB - AIMS: The purpose of this study was to investigate the characteristics of cisplatin-induced C57 mouse cochlear hair cell damage in vitro. METHODS: Forty seven cochleae harvested from 2- to 4-day-old C57 mice were used. Forty specimens were treated with different concentrations of cisplatin (10, 25, 50, 100, 400, and 1,000 MUmol/l) for 48 h. The remaining seven specimens were used as a control group. RESULTS: The rate of hair cell loss increased from 14.5 to 78.4% over cisplatin concentrations of 10 to 100 MUmol/l, whereas hair cell loss decreased to 48.8 and 8.77% at concentrations of 400 and 1,000 MUmol/l, respectively. Apoptosis was detected by DAPI staining in the areas of hair cell damage. Hair cell loss rates differed significantly among the cisplatin-treated groups. Linear regression analysis of cisplatin dose versus hair cell number showed a significant negative correlation for cisplatin doses up to 100 MUmol/l and a positive correlation with further increases up to 1,000 MUmol/l. CONCLUSIONS: We conclude that cisplatin-induced hair cell damage was concentration dependent only up to a certain dose and that injury resistance may occur in cochlear cells treated with higher doses of cisplatin. PMID- 27270731 TI - Dnmt2/Trdmt1 as Mediator of RNA Polymerase II Transcriptional Activity in Cardiac Growth. AB - Dnmt2/Trdmt1 is a methyltransferase, which has been shown to methylate tRNAs. Deficient mutants were reported to exhibit various, seemingly unrelated, defects in development and RNA-mediated epigenetic heredity. Here we report a role in a distinct developmental regulation effected by a noncoding RNA. We show that Dnmt2 deficiency in mice results in cardiac hypertrophy. Echocardiographic measurements revealed that cardiac function is preserved notwithstanding the increased dimensions of the organ due to cardiomyocyte enlargement. Mechanistically, activation of the P-TEFb complex, a critical step for cardiac growth, results from increased dissociation of the negatively regulating Rn7sk non-coding RNA component in Dnmt2-deficient cells. Our data suggest that Dnmt2 plays an unexpected role for regulation of cardiac growth by modulating activity of the P TEFb complex. PMID- 27270733 TI - Use of In Vitro Transcription System for Analysis of Corynebacterium glutamicum Promoters Recognized by Two Sigma Factors. AB - Promoter activities in Corynebacterium glutamicum strains with deletions of genes encoding sigma factors of RNA polymerase suggested that transcription from some promoters is controlled by two sigma factors. To prove that different sigma factors are involved in the recognition of selected Corynebacterium glutamicum promoters, in vitro transcription system was applied. It was found that a typical housekeeping promoter Pper interacts with the alternative sigma factor sigma(B) in addition to the primary sigma factor sigma(A). On the other way round, the sigma(B)-dependent promoter of the pqo gene that is expressed mainly in the stationary growth phase was active also with sigma(A). Some promoters of genes involved in stress responses (P1clgR, P2dnaK, and P2dnaJ2) were found to be recognized by two stress-responding sigma factors, sigma(H) and sigma(E). In vitro transcription system thus proved to be a useful direct technique for demonstrating the overlap of different sigma factors in recognition of individual promoters in C. glutamicum. PMID- 27270732 TI - Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study. AB - AIM: To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity) over time. METHODS: A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linkoping at age 8, and the same 107 children from Linkoping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the general Swedish child population, and on an average lean. RESULTS: High physical activity was related to lower C-peptide at age 8 and 12. This correlation was especially pronounced in boys, who also were more physically active than girls at both time points. The association seen at 8 years of age was similar at age 12 in most children. Children with higher BMI Z-Score had a higher fasting C-peptide (age 12) but linear regression showed that children with more steps per day were less likely to have a higher fasting C-peptide irrespective of BMI. Longitudinal follow-up showed that a decrease in physical activity increased insulin resistance and beta-cell load. CONCLUSIONS: Already in young children, physical activity improves insulin sensitivity and decreases the need of C peptide over time. This seems to become even more pronounced with increasing age when children are followed longitudinally. Low physical activity increases the load on insulin producing beta-cells, might increase the risk for both type 1- and 2 diabetes. PMID- 27270734 TI - Prevalence and Associated Factors of Erectile Dysfunction in Patients With Moderate to Severe Psoriasis and Healthy Population: A Comparative Study Considering Physical and Psychological Factors. AB - Recent studies have shown that psoriasis is associated with an increased prevalence of erectile dysfunction. To our knowledge, no comparative study has considered simultaneously the role of organic factors and psychological factors in this process. We performed a prospective case series study matched by age to explore the prevalence of erectile dysfunction in psoriasis patients compared to a healthy population and to investigate the role of anxiety, depression, and cardiovascular risk factors in the relationship between psoriasis and erectile dysfunction. The healthy group was matched by frequency to cases by age. Seventy nine patients with moderate to severe psoriasis and 79 healthy controls participated in the study. Participants completed the Massachusetts General Hospital Sexual Functioning Questionnaire and the Hospital Anxiety and Depression Scale. Psoriasis patients had an increased prevalence of erectile dysfunction in comparison to controls, 34.2 vs. 17.7 % (p < .05). Multivariate analysis showed a significant association between erectile dysfunction and age, smoking and anxiety/depression, but not with psoriasis per se. In conclusion, the higher prevalence of smoking and anxiety/depression among patients with moderate to severe psoriasis probably explains the higher prevalence of erectile dysfunction in this population. PMID- 27270735 TI - Group-level differences in visual search asymmetry. AB - East Asians and Westerners differ in various aspects of perception and cognition. For example, visual memory for East Asians is believed to be more influenced by the contextual aspects of a scene than is the case for Westerners (Masuda & Nisbett in Journal of Personality and Social Psychology, 81, 922-934, 2001). There are also differences in visual search: For Westerners, search is faster for a long line among short ones than for a short line among long ones, whereas this difference does not appear to hold for East Asians (Ueda et al., 2016). However, it is unclear how these group-level differences originate. To investigate the extent to which they depend upon environment, we tested visual search and visual memory in East Asian immigrants who had lived in Canada for different amounts of time. Recent immigrants were found to exhibit no search asymmetry, unlike Westerners who had spent their lives in Canada. However, immigrants who had lived in Canada for more than 2 years showed performance comparable to that of Westerners. These differences could not be explained by the general analytic/holistic processing distinction believed to differentiate Westerners and East Asians, since all observers showed a strong holistic tendency for visual recognition. The results instead support the suggestion that exposure to a new environment can significantly affect the particular processes used to perceive a given stimulus. PMID- 27270736 TI - Stroking me softly: Body-related effects in effect-based action control. AB - Empirical investigations of ideomotor effect anticipations have mainly focused on action effects in the environment. By contrast, action effects that apply to the agent's body have rarely been put to the test in corresponding experimental paradigms. We present a series of experiments using the response-effect compatibility paradigm, in which we studied the impacts of to-be-produced tactile action effects on action selection, initiation, and execution. The results showed a robust and reliable impact if these tactile action effects were rendered task relevant (Exp. 1), but not when they were task-irrelevant (Exps. 2a and 2b). We further showed that anticipations of tactile action effects follow the same time course as anticipations of environment-related effects (Exps. 3 and 4). These findings demonstrate that body-related action effects affect action control much as environment-related effects do, and therefore support the theoretical assumption of the functional equivalence of all types of action effects. PMID- 27270737 TI - Opportunities and Challenges of Global Mental Health. PMID- 27270738 TI - The 2013 Canadian Forces Mental Health Survey: Background and Methods. AB - OBJECTIVE: The 2013 Canadian Forces Mental Health Survey (CFMHS) collected detailed information on mental health problems, their impacts, occupational and nonoccupational determinants of mental health, and the use of mental health services from a random sample of 8200 serving personnel. The objective of this article is to provide a firm scientific foundation for understanding and interpreting the CFMHS findings. METHODS: This narrative review first provides a snapshot of the Canadian Armed Forces (CAF), focusing on 2 key determinants of mental health: the deployment of more than 40,000 personnel in support of the mission in Afghanistan and the extensive renewal of the CAF mental health system. The findings of recent population-based CAF mental health research are reviewed, with a focus on findings from the very similar mental health survey done in 2002. Finally, key aspects of the methods of the 2013 CFMHS are presented. RESULTS: The findings of 20 peer-reviewed publications using the 2002 mental health survey data are reviewed, along with those of 25 publications from other major CAF mental health research projects executed over the past decade. CONCLUSIONS: More than a decade of population-based mental health research in the CAF has provided a detailed picture of its mental health and use of mental health services. This knowledge base and the homology of the 2013 survey with the 2002 CAF survey and general population surveys in 2002 and 2012 will provide an unusual opportunity to use the CFMHS to situate mental health in the CAF in a historical and societal perspective. PMID- 27270740 TI - Perceived Need for and Perceived Sufficiency of Mental Health Care in the Canadian Armed Forces: Changes in the Past Decade and Comparisons to the General Population. AB - OBJECTIVES: Failure to perceive need for care (PNC) is the leading barrier to accessing mental health care. After accessing care, many individuals perceive that their needs were unmet or only partially met, an additional problem related to perceived sufficiency of care (PSC). The Canadian Armed Forces (CAF) invested heavily in workplace mental health in the past decade to improve PNC/PSC; yet, the impact of these investments remains unknown. To assess the impact of these investments, this study 1) captures changes in PNC/PSC over the past decade in the CAF and 2) compares current PNC/PSC between the CAF and civilians. METHODS: Data were drawn from the 2013 and 2002 CAF surveys and the 2012 civilian mental health survey (total N = ~40 000), conducted by Statistics Canada using similar methodology. Exclusions were applied to the civilian sample to make them comparable to the military sample. Prevalence rates for No need, Need met, Need partially met, and Need unmet categories across service types (Information, Medication, Counselling and therapy, Any services) were calculated and compared between 1) the 2 CAF surveys and 2) the 2013 CAF and 2012 civilian surveys after sample matching. RESULTS: Reports of Any need and Need met were higher in the CAF in 2013 than in 2002 by approximately 6% to 8% and 2% to 8%, respectively, and higher in the CAF than in civilians by 3% to 10% and 2% to 8%, respectively. CONCLUSIONS: These results suggest that investments in workplace mental health, such as those implemented in the CAF, can lead to improvements in recognizing the need for care (PNC) and subsequently getting those needs met (PSC). PMID- 27270739 TI - Prevalence of Past-Year Mental Disorders in the Canadian Armed Forces, 2002-2013. AB - OBJECTIVE: More than 40,000 Canadian Armed Forces (CAF) personnel have deployed in support of the mission in Afghanistan since 2002. Over the same period, the CAF strengthened its mental health system. This article explores the effect of these events on the prevalence of past-year mental disorders over the period 2002 2013. METHOD: The data sources were 2 highly comparable population-based mental health surveys of CAF Regular Force personnel done in 2002 and 2013 (n = 5155 and 6996, respectively). Data were collected via in-person interviews with Statistics Canada personnel using the World Health Organization's Composite International Diagnostic Interview to assess past-year disorders. RESULTS: In 2013, 16.5% had 1 or more of the 6 past-year disorders assessed in the survey, with the most common conditions being major depressive episode (MDE), posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD), which affected 8.0%, 5.3%, and 4.7%, respectively. The prevalence of PTSD, GAD, and panic disorder has increased significantly since 2002 (adjusted odds ratios from logistic regression models = 2.1, 3.0, and 1.9, respectively), while no change was seen for MDE. The comorbidity of mood and anxiety disorders increased significantly over time, being seen in 27.4% and 41.0% of those with mental disorders in 2002 and 2013, respectively. CONCLUSION: There has been an increase in the prevalence of PTSD and other anxiety disorders and of the extent of comorbidity of mood and anxiety disorders in CAF personnel over the period 2002-2013. PMID- 27270741 TI - Prevalence Comparison of Past-year Mental Disorders and Suicidal Behaviours in the Canadian Armed Forces and the Canadian General Population. AB - OBJECTIVE: Military personnel in Canada and elsewhere have been found to have higher rates of certain mental disorders relative to their corresponding general populations. However, published Canadian data have only adjusted for age and sex differences between the populations. Additional differences in the sociodemographic composition, labour force characteristics, and childhood trauma exposure in the populations could be driving these prevalence differences. Our objective is to compare the prevalence of past-year mental disorders and suicidal behaviours in the Canadian Armed Forces Regular Force with the rates in a representative, matched sample of Canadians in the general population (CGP). METHODS: Data sources were the 2013 Canadian Forces Mental Health Survey and the 2012 Canadian Community Health Survey-Mental Health. CGP sample was restricted to match the age range, employment status, and history of chronic conditions of Regular Force personnel. An iterative proportional fitting method was used to approximate the marginal distribution of sociodemographic and childhood trauma variables in both samples. RESULTS: Relative to the matched CGP, Regular Force personnel had significantly higher rates of past-year major depressive episode, generalized anxiety disorder, and suicide ideation. However, lower rates of alcohol use disorder were seen in Regular Force personnel relative to the matched CGP sample. CONCLUSIONS: Factors other than differences in sociodemographic composition and history of childhood trauma account for the excess burden of mental disorders and suicidal behaviours in the Canadian Armed Forces. Explanations to explore in future research include occupational trauma, selection effects, and differences in the context of administration of the 2 surveys. PMID- 27270742 TI - Mental Health in the Canadian Armed Forces: New Data, New Answers, and New Questions. PMID- 27270744 TI - Contribution of the Mission in Afghanistan to the Burden of Past-Year Mental Disorders in Canadian Armed Forces Personnel, 2013. AB - OBJECTIVE: The purpose of this study was to estimate the contribution of the mission in Afghanistan to the burden of mental health problems in the Canadian Armed Forces (CAF). METHODS: Data were obtained from the 2013 Canadian Forces Mental Health Survey, which assessed mental disorders using the World Health Organization's Composite International Diagnostic Interview. The sample consisted of 6696 Regular Force (RegF) personnel, 3384 of whom had deployed in support of the mission. We estimated the association of past-year mental health problems with Afghanistan deployment status, adjusting for covariates using logistic regression; population attributable fractions (PAFs) were also calculated. RESULTS: Indication of a past-year mental disorder was identified in 18.4% (95% confidence interval [CI], 17.0% to 19.7%) of Afghanistan deployers compared with 14.6% (95% CI, 13.3% to 15.8%) in others. Afghanistan-related deployments contributed to the burden of a past-year disorder (PAF = 8.7%; 95% CI, 3.0% to 14.2%), with the highest PAFs being seen for panic disorder (34.7%) and posttraumatic stress disorder (32.1%). The PAFs for individual alcohol use disorders and suicide ideation were not different from zero. Child abuse, however, had a much greater PAF for any past-year disorder (28.7%; 95% CI, 23.4% to 33.7%) than did the Afghanistan mission. CONCLUSIONS: The mission in Afghanistan contributed significantly to the burden of mental disorders in the CAF RegF in 2013. However, the much stronger contribution of child abuse highlights the need for strong military mental health systems, even in peacetime, and the need to target the full range of determinants of mental health in prevention and control efforts. PMID- 27270743 TI - Disability and Mental Disorders in the Canadian Armed Forces. AB - OBJECTIVES: The initial goal was to validate the use of a self-report measure of disability in the Canadian Armed Forces (CAF). The main goal was to document the extent of disability in personnel with and without mental disorders. METHODS: Data were obtained from the 2013 Canadian Forces Mental Health Survey; the sample included 6700 Regular Forces personnel. Disability was measured with the 12-item version of the World Health Organization Disability Assessment Schedule (WHODAS 2); established cut points were used to demarcate severe, moderate, minimal, and no disability. The following recent (past-year) and remote (lifetime but not past year) disorders were assessed with diagnostic interviews: posttraumatic stress disorder, major depressive episode, generalized anxiety disorder, panic disorder, and alcohol use disorder. RESULTS: The WHODAS-2 showed good internal consistency (alpha = 0.89) and a 1-factor structure. Most personnel had no disability (59.2%) or minimal disability (30.8%). However, an important minority had moderate or severe disability (8.4% and 1.6%, respectively). Individuals with recent disorders reported greater disability than those without lifetime disorders, although many had minimal or no disability (41.2% and 24.7%, respectively). Disability increased with the number of recent disorders. Relative to those without lifetime disorders, individuals with remote disorders showed slightly greater disability, but most had no disabilty (57.1%) or minimal disability (35.0%). CONCLUSIONS: The 12-item WHODAS-2 is a valid measure of disability in the CAF. Mental disorders may be important drivers of disability in this population, although limited residual disability is seen in individuals with remote disorders. PMID- 27270745 TI - Accountability for the Psychological Costs of Military Service: A Benchmark Set by the Canadian Armed Forces. PMID- 27270746 TI - Electron transfer pathways of formate-driven H2 production in Desulfovibrio. AB - The potential of sulfate-reducing bacteria (SRB) as biocatalysts for H2 production from formate was recently demonstrated, but the electron transfer pathways involved were not described. In the present work, we analyzed the H2 production capacity of five Desulfovibrio strains: Desulfovibrio vulgaris, Desulfovibrio desulfuricans, Desulfovibrio alaskensis, Desulfovibrio fructosivorans, and Desulfovibrio gigas. D. vulgaris showed the highest H2 productivity (865 mL Lmedium (-1)), and D. gigas the lowest one (374 mL Lmedium ( 1) of H2). The electron transfer pathways involved in formate-driven H2 production by these two organisms were further investigated through the study of deletion mutants of hydrogenases (Hases) and formate dehydrogenases (Fdhs). In D. vulgaris, the periplasmic FdhAB is the key enzyme for formate oxidation and two pathways are apparently involved in the production of H2 from formate: a direct one only involving periplasmic enzymes and a second one that involves transmembrane electron transfer and may allow energy conservation. In the presence of selenium, the Hys [NiFeSe] Hase is the main periplasmic enzyme responsible for H2 production, and the cytoplasmic Coo Hase is apparently involved in the ability of D. vulgaris to grow by converting formate to H2, in sparging conditions. Contrary to D. vulgaris, H2 production in D. gigas occurs exclusively by the direct periplasmic route and does not involve the single cytoplasmic Hase, Ech. This is the first report of the metabolic pathways involved in formate metabolism in the absence of sulfate in SRB, revealing that the electron transfer pathways are species-specific. PMID- 27270747 TI - Evaluating Nursery Phototherapy Use and Discharge Practices After the Creation of a Weekend Newborn Clinic. PMID- 27270748 TI - Comprehensive review of vascularized lymph node transfers for lymphedema: Outcomes and complications. AB - INTRODUCTION: Lymphedema remains a challenging clinical problem. A new field of lymphatic surgery using micro and super microsurgery techniques is a rapidly advancing field aimed to treat recalcitrant cases. The objective of this study was to evaluate outcomes and complications of vascularized lymph node transfer (VLNT). Several early preliminary studies have reported promising outcomes, but they are limited by small numbers, short follow-up, and are inconsistent in addressing the origin and recipient site of the transferred lymph nodes as well as the donor site morbidity. METHODS: A review of literature was conducted using PubMed-MEDLINE, EMBASE for key words vascularized lymph node transfer (also autologous, lymph node transplant). Only human studies were included. RESULTS: A total 24 studies encompassing 271 vascularized lymph node transfers were included. The inguinal nodes were the most commonly used donor site followed by the lateral thoracic lymph nodes. The lateral thoracic lymph nodes were the least effective and had the highest complication rates (27.5%) compared to other lymph node donor sites (inguinal: 10.3% and supraclavicular: 5.6%). Upper extremity lymphedema responded better compared to lower extremity (74.2 vs. 53.2%), but there was no difference in placing the lymph nodes more proximally versus distally on the extremity (proximal: 76.9% vs. distal: 80.4%). CONCLUSION: Vascularized lymph node transfer for lymphedema treatment is a promising operative technique showing beneficial results in early but also in advanced stage lymphedema. This physiologic surgical procedure should be included in a modern reconstructive concept for lymphedema treatment. (c) 2016 Wiley Periodicals, Inc. Microsurgery 38:222-229, 2018. PMID- 27270749 TI - Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut): An Extension of the STROBE Statement. AB - BACKGROUND: Concerns have been raised about the quality of reporting in nutritional epidemiology. Research reporting guidelines such as the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement can improve quality of reporting in observational studies. Herein, we propose recommendations for reporting nutritional epidemiology and dietary assessment research by extending the STROBE statement into Strengthening the Reporting of Observational Studies in Epidemiology-Nutritional Epidemiology (STROBE-nut). METHODS AND FINDINGS: Recommendations for the reporting of nutritional epidemiology and dietary assessment research were developed following a systematic and consultative process, coordinated by a multidisciplinary group of 21 experts. Consensus on reporting guidelines was reached through a three-round Delphi consultation process with 53 external experts. In total, 24 recommendations for nutritional epidemiology were added to the STROBE checklist. CONCLUSION: When used appropriately, reporting guidelines for nutritional epidemiology can contribute to improve reporting of observational studies with a focus on diet and health. PMID- 27270751 TI - Energetic aminated-azole assemblies from intramolecular and intermolecular N-HO and N-HN hydrogen bonds. AB - Compounds with adjacent C-NO2, C-NH2 and N-NH2 groups were designed and synthesized via amination. Their structures were characterized by infrared, and multinuclear NMR spectroscopy, elemental analysis, and X-ray single crystal diffraction. The effect of intramolecular and intermolecular N-HO and N-HN hydrogen bonds is discussed. Detonation properties were calculated by EXPLO 5 software based on calculated HOFs and experimental densities. PMID- 27270750 TI - SNX27, a protein involved in down syndrome, regulates GPR17 trafficking and oligodendrocyte differentiation. AB - The G protein-coupled receptor 17 (GPR17) plays crucial roles in myelination. It is highly expressed during transition of oligodendrocyte progenitor cells to immature oligodendrocytes, but, after this stage, it must be down-regulated to allow generation of mature myelinating cells. After endocytosis, GPR17 is sorted into lysosomes for degradation or recycled to the plasma membrane. Balance between degradation and recycling is important for modulation of receptor levels at the cell surface and thus for the silencing/activation of GPR17-signaling pathways that, in turn, affect oligodendrocyte differentiation. The molecular mechanisms at the basis of these processes are still partially unknown and their characterization will allow a better understanding of myelination and provide cues to interpret the consequences of GPR17 dysfunction in diseases. Here, we demonstrate that the endocytic trafficking of GPR17 is mediated by the interaction of a type I PDZ-binding motif located at the C-terminus of the receptor and SNX27, a recently identified protein of the endosome-associated retromer complex and whose functions in oligodendrocytes have never been studied. SNX27 knock-down significantly reduces GPR17 plasma membrane recycling in differentiating oligodendrocytes while accelerating cells' terminal maturation. Interestingly, trisomy-linked down-regulation of SNX27 expression in the brain of Ts65Dn mice, a model of Down syndrome, correlates with a decrease in GPR17(+) cells and an increase in mature oligodendrocytes, which, however, fail in reaching full maturation, eventually leading to hypomyelination. Our data demonstrate that SNX27 modulates GPR17 plasma membrane recycling and stability, and that disruption of the SNX27/GPR17 interaction might contribute to pathological oligodendrocyte differentiation defects. GLIA 2016. GLIA 2016;64:1437-1460. PMID- 27270752 TI - Effects of Curcuminoid Pyrazoles on Cancer Cells and on the Expression of Telomerase Related Genes. AB - A group of 13 curcuminoid pyrazoles was investigated for their cytotoxicity on three tumoral cell lines (HT-29, MCF-7, and HeLa) and one non-tumoral human cell line (HEK-293). The values obtained were compared with those of curcumin. A subset of selected derivatives was also studied for their ability to downregulate expression of the hTERT and c-Myc genes, which are both involved in telomerase activity. PMID- 27270753 TI - The use of Ocimum americanum essential oil against the pathogens Aeromonas hydrophila and Gyrodactylus sp. in silver catfish (Rhamdia quelen). AB - The bactericidal activity (minimum inhibitory concentration (MIC)-test) of Ocimum americanum (inflorescences) essential oil (OAEO) against Aeromonas hydrophila was determined in this study. Also investigated was the potential of OAEO and the main compound found in the oil (linalool) at subinhibitory concentrations to be inhibitors of haemolysis caused by Aer. hydrophila in fish erythrocytes. An in vivo experiment was conducted to evaluate the survival of fish (Rhamdia quelen) experimentally infected with Aer. hydrophila and exposed to OAEO. A second experiment was conducted to evaluate the in vitro and in vivo activity of OAEO (mix from inflorescences and leaves) against the parasite Gyrodactylus sp. The OAEO showed weak in vitro activity against Aer. hydrophila (6400 MUg ml(-1) ). Subinhibitory concentrations of OAEO (100 MUg ml(-1) ) inhibited haemolysis (90%) caused by Aer. hydrophila in fish erythrocytes, however, linalool did not inhibit haemolysis activity. At the low concentrations (10 and 20 mg l(-1) ) added to the water, OAEO promoted the survival of fish experimentally infected with Aer. hydrophila. Lastly, the OAEO mix (50 mg l(-1) ) was effective against Gyrodactylus sp., significantly reducing (60%) the number of parasites in the fish. SIGNIFICANCE AND IMPACT OF THE STUDY: Phytochemicals, such as essential oils (EOs) are a great source of new molecules and have shown potential to be used in aquaculture systems. However, additional studies focused on the in vivo efficacy, mode of action and identification of the active compounds are needed. This study determined the potential of Ocimum americanum EO for use against two important fish pathogens, Aeromonas hydrophila and Gyrodactylus sp., as well as providing preliminary information about the role of the main EO compound (linalool) against Aer. hydrophila virulence. PMID- 27270754 TI - Sex differences in neural and behavioral signatures of cooperation revealed by fNIRS hyperscanning. AB - Researchers from multiple fields have sought to understand how sex moderates human social behavior. While over 50 years of research has revealed differences in cooperation behavior of males and females, the underlying neural correlates of these sex differences have not been explained. A missing and fundamental element of this puzzle is an understanding of how the sex composition of an interacting dyad influences the brain and behavior during cooperation. Using fNIRS-based hyperscanning in 111 same- and mixed-sex dyads, we identified significant behavioral and neural sex-related differences in association with a computer based cooperation task. Dyads containing at least one male demonstrated significantly higher behavioral performance than female/female dyads. Individual males and females showed significant activation in the right frontopolar and right inferior prefrontal cortices, although this activation was greater in females compared to males. Female/female dyad's exhibited significant inter-brain coherence within the right temporal cortex, while significant coherence in male/male dyads occurred in the right inferior prefrontal cortex. Significant coherence was not observed in mixed-sex dyads. Finally, for same-sex dyads only, task-related inter-brain coherence was positively correlated with cooperation task performance. Our results highlight multiple important and previously undetected influences of sex on concurrent neural and behavioral signatures of cooperation. PMID- 27270755 TI - Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health. AB - Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host-microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting from microbiome-host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host-microbe interactions may be novel targets for interventions aimed at improving nutrition and human health. PMID- 27270756 TI - Clinicopathological characteristics predict lymph node metastases in ypT0-2 rectal cancer after chemoradiotherapy. AB - AIMS: Changes in rectal cancer treatment include increasing emphasis on organ preservation. Local excision after chemoradiotherapy (CRT) for rectal cancer with excellent clinical response reduces morbidity and mortality compared to total mesorectal excision, although residual lymph node metastases (LNM) may cause local recurrence. Our aim is to identify clinicopathological factors predicting the presence of residual LNM in rectal cancer patients with ypT0-2 tumours after neoadjuvant CRT. These risk factors may help to select patients who can be spared radical surgery without compromising oncological outcomes. METHODS AND RESULTS: Rectal cancer patients with ypT0-2 tumours after CRT and radical resection from five centres treated between June 1999 and February 2012 were included. Histopathology was reviewed extensively. Clinicopathological characteristics and their association with residual LNM were investigated. Of 657 consecutive CRT treated rectal cancer patients 210 with ypT0-2 disease were included. Residual nodal disease was found in 44 cases (21.0%). Independent predictors of LNM were clinical nodal involvement (cN+ ) [odds ratio (OR): 2.79, 95% confidence interval (CI): 1.04-7.48, P = 0.042], high-grade histopathology assessed in the post-CRT resection specimen (OR: 6.46, 95% CI: 1.23-34.02, P = 0.028) and residual tumour diameter (RTD) >=10 mm (OR: 2.54, 95% CI: 1.06-6.09, P = 0.036). An algorithm combining these factors stratified patients adequately according to LNM risk, independently of ypT category. CONCLUSIONS: Clinical nodal involvement, high grade histopathology and RTD >=10 mm are strong and independent predictors of residual nodal disease in rectal cancer patients with ypT0-2 tumours after CRT. Risk stratification based on these factors may help to identify patients suitable for organ preserving therapy and should be validated in appropriately selected populations. PMID- 27270757 TI - Reassortment compatibility between PB1, PB2, and HA genes of the two influenza B virus lineages in mammalian cells. AB - In addition to influenza A subtypes, two distinct lineages of influenza B virus also cause seasonal epidemics to humans. Recently, Dudas et al. have done evolutionary analyses of reassortment patterns of the virus and suggested genetic lineage relationship between PB1, PB2, and HA genes. Using genetic plasmids and reassortant viruses, we here demonstrate that a homologous lineage PB1-PB2 pair exhibits better compatibility than a heterologous one and that the lineage relationship between PB1 and HA is more important for viral replication than that between PB2 and HA. However, co-adaptation of PB1-PB2-HA genes appears to be affected by complete gene constellation. PMID- 27270758 TI - Low occurrence of ventricular arrhythmias after alcohol septal ablation in high risk patients with hypertrophic obstructive cardiomyopathy. AB - INTRODUCTION: Percutaneous alcohol septal ablation (PTSMA) is an established treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). However, there is concern of a higher risk for ventricular tachyarrhythmias and sudden death due to the myocardial scar created after PTSMA. We investigated the possibility of increased ventricular arrhythmias and risk of sudden death after PTSMA in a subgroup of patients with an already implanted ICD. METHODS AND RESULTS: Between 2009 and 2012, 239 PTSMAs were performed in 212 patients with HOCM. In 32 of those an ICD had already been implanted before PTSMA for primary (31 patients) or secondary (1 patient) prevention of sudden death. The maximum left ventricular outflow tract gradient (LVOTG) was reduced from 114 +/- 39 mmHg before PTSMA to 23 +/- 19 mmHg (P < 0.0001). Among clinical risk factors for sudden death, nonsustained ventricular tachycardia (VT), syncope and family history for sudden death were most common. After a median follow-up of 5.3 (IQR 4.3-5.7) years after PTSMA only one patient had ICD shocks (annual ICD discharge 0.6 %). In another 3 patients, with already documented nonsustained VTs as risk factor before ICD implantation, VT episodes that activated antitachycardic pacing were recorded. The annual appropriate ICD intervention including all events was 2.5 % and involved only patients with a very high estimated 5-year sudden death risk before PTSMA (>14.3 %). CONCLUSIONS: In a selected high-risk patient cohort with HOCM ominous arrhythmic events seem to be rare and predominantly occur in patients with a very high estimated risk of sudden death before PTSMA. PMID- 27270759 TI - Clinical characteristics and treatment of renal artery fibromuscular dysplasia with percutaneous transluminal angioplasty: a long-term follow-up study. AB - BACKGROUND: Renal artery fibromuscular dysplasia (RAFMD) is a non-atherosclerotic cause of renal artery stenosis often affecting the young. Percutaneous transluminal renal angioplasty (PTRA) is the treatment of choice but there are few studies of the outcome of the procedure. METHODS: This retrospective analysis included 64 patients (56.2 % female; mean age at diagnosis, 28.0 years) with RAFMD who underwent PTRA between November 2003 and August 2015. Technical and clinical success rates and restenosis rates were evaluated. RESULTS: Seventy-six procedures were performed on 64 RAFMD patients. Technical success was 96.9 %, as defined by <30 % residual stenosis, with stent placement required in 11 patients (17.2 %). In the short term (1 month), the majority (79.7 %) had an immediate clinical benefit, with cure of hypertension in 35.9 %, and improvement in hypertension and a lower requirement for antihypertensive medications in 43.8 %. In the long term (mean, 47.5 months; range, 5-141 months), the survival rate was 96.9 %, freedom from restenosis was 84.4 %, and 76.6 % of patients showed a sustained clinical benefit (cure rate 40.6 %, improvement rate 35.9 %). Eight patients were treated with a second procedure and two had a third procedure, with half of these patients showing an improvement in hypertension. CONCLUSION: PTRA for symptomatic RAFMD is safe and clinically successful. More than half of patients experience an immediate clinical benefit with sustained long-term effects. For patients with restenosis, there was a good response to a second PTRA. PMID- 27270760 TI - Diagnostic value of speckle-tracking echocardiography in confirmed cardiac sarcoidosis. PMID- 27270762 TI - CT dose reduction: approaches, strategies and results from a province-wide program in Quebec. AB - Many studies have shown a statistically significant increase of life-time risk of radiation-induced cancer from CT examinations. In this context, in Canada, the Quebec's provincial clinical center of expertise in radiation safety (CECR) has led a province-wide tour of 180 CT installations in order to: (i) evaluate the technical and functional performance of CT scanners, (ii) evaluate and improve radiation safety practices and (iii) initiate, with local teams, a CT dose optimization process. The CT tour consisted of a two day visit of CT installations by a CECR multidisciplinary team of medical physicists, engineers and medical imaging technologists (MITs) carried out in close collaboration with local teams composed of MITs, radiologists, physicists, engineers and managers. The CECR has evaluated 112 CT scanners since 2011. Optimization of CT protocols was performed in all centers visited. The average dose reduction obtained from optimization was [Formula: see text], [Formula: see text] and [Formula: see text] for adult head, thorax and abdomen-pelvis, respectively. The main recommendations often made by the CECR experts were: (1) the implementation of low-dose protocols for the follow-up of pulmonary nodules and for renal calculi, (2) the compliance to the prescribed scan range as defined by local guidelines, (3) the correct positioning of patients and (4) the use of bismuth shielding to reduce the dose to radiosensitive organs. The CECR approach to optimize CT doses to patients is based on the active participation of local stakeholders and takes into account the performance of CT scanners. The clinical requirements as expressed by radiologists remain at the core of the optimization process. PMID- 27270761 TI - Carotid Artery Stenting With Proximal Embolic Protection via a Transradial or Transbrachial Approach: Pushing the Boundaries of the Technique While Maintaining Safety and Efficacy. AB - PURPOSE: To compare the feasibility and safety of proximal cerebral protection to a distal filter during carotid artery stenting (CAS) via a transbrachial (TB) or transradial (TR) approach. METHODS: Among 856 patients who underwent CAS between January 2007 and July 2015, 214 (25%) patients (mean age 72+/-8 years; 154 men) had the procedure via a TR (n=154) or TB (n=60) approach with either Mo.MA proximal protection (n=61) or distal filter protection (n=153). The Mo.MA group (mean age 73+/-7 years; 54 men) had significantly more men and more severe stenosis than the filter group (mean age 71+/-8 years; 100 men). Stent type and CAS technique were left to operator discretion. Heparin and a dedicated closure device or bivalirudin and manual compression were used in TR and TB accesses, respectively. Technical and procedure success, crossover to femoral artery, 30 day major adverse cardiovascular/cerebrovascular events (MACCE; death, all strokes, and myocardial infarction), vascular complications, and radiation exposure were compared between groups. RESULTS: Crossover to a femoral approach was required in 1/61 (1.6%) Mo.MA patient vs 11/153 (7.1%) filter patients mainly due to technical difficulty in engaging the target vessel. Five Mo.MA patients developed acute intolerance to proximal occlusion; 4 were successfully shifted to filter protection. A TR patient was shifted to filter because the Mo.MA system was too short. CAS was technically successful in the remaining 55 (90%) Mo.MA patients and 142 (93%) filter patients. The MACCE rate was 0% in the Mo.MA patients and 2.8% in the filter group (p=0.18). Radiation exposure was similar between groups. Major vascular complications occurred in 1/61 (1.6%) and in 3/153 (1.96%) patients in the Mo.MA and filter groups (p=0.18), respectively, and were confined to the TB approach in the early part of the learning curve. Chronic radial artery occlusion was detected by Doppler ultrasound in 2/30 (6.6%) Mo.MA patients and in 4/124 (3.2%) filter patients by clinical assessment (p=0.25) at 8.1+/-7.5-month follow-up. CONCLUSION: CAS with proximal protection via a TR or TB approach is a feasible, safe, and effective technique with a low rate of vascular complications. PMID- 27270763 TI - Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system. AB - Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. (c) 2016 American Cancer Society. PMID- 27270764 TI - Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines. AB - Monoclonal antibody YHD-06 generated by immunization with GM2 reacted with gangliosides with GM2-determinant, i.e., GM2, GalNAc-GM1b and GalNAc-GD1a, among which GalNAc-GD1a was characterized as an antigen of autoimmune peripheral neuropathies including Guillain-Barre syndrome. When glycolipids were examined by TLC-immunostaining with YHD-06 in seven human cervical carcinoma-derived cell lines, GM2 was found in all cell lines, amounting to 15.5 % to 57.5 % of total gangliosides. Whereas GalNAc-GD1a was present in three cell lines, amounting to 5.4-17.5 % of total gangliosides, and GalNAc-GM1b in four cell lines in amounts of less than 2 %. The elevated amounts of gangliosides with GM2 determinant were closely correlated with the relative intensities of gene expression of GalNAc transferase, this being characteristic of cervical carcinoma-derived cells. However, in tissues from patients with several histological types of cervical carcinomas, GM3 was ubiquitously expressed in amounts of more than 66 % of total gangliosides, GM2 was expressed in only five of 15 tissues, and both GalNAc-GM1b and GalNAc-GD1a were not even detected in trace amounts. Since GM1 was detected in all tissues in amounts of less than 0.06 MUg/mg dried tissue, all cervical carcinoma tissues were revealed to exhibit GM2 synthesis, indicating that enhanced synthesis of gangliosides with GM2 determinant is a characteristic of cultivated cells in vitro. Similarly, although I(3)SO3-GalCer was not present in the squamous cell carcinoma (SCC) tissues, SCC-derived cells selectively expressed II(3)SO3-LacCer. Since enhanced synthesis of GM2 has been reported in SV-40 virus-transfected fibroblasts, papilloma virus might be involved in the expression of GM2 in cervical carcinoma-derived cells. PMID- 27270767 TI - Delegation paves way for US-Cuba research collaborations. PMID- 27270765 TI - RAGE and glyoxalase in kidney disease. AB - Glycation is an important reaction in the regulation of physiological state. When poorly controlled, however, glycation can also result in the accumulation of glycated proteins (advanced glycation endproducts; AGEs) in the body. This AGE accumulation is termed glycative stress, and is an established pathological factor: to date, glycative stress has been closely associated with not only kidney diseases, but also kidney aging. Accumulating evidence demonstrates that the progression of renal tubular damage and tubular aging are often correlated with activation of the receptor for the AGE (RAGE)-AGE pathway or decreased activity of glyoxalase 1, which is an anti-glycation enzyme to lower glycative stress. Further, glycative stress exacerbates the derangement of protein homeostasis: the posttranslationally modified proteins by glycation often lose or gain their functions. Such deranged protein homeostasis leads to endoplasmic reticulum (ER) stress, a state of ER dysfunction in which the quality control of proteins is defective, as well as to induction of its stress signal, the unfolded protein response (UPR), in the kidney. The lowering of glycative stress via modulation of RAGE-AGE axis or glyoxalase 1 activity is beneficial for tubular homeostasis and the subsequent prevention and treatment of kidney disease, suggesting the possibility of novel therapeutic approaches which target glycative stress. In this review, we focused on the impact of glycative stress in the kidney, especially the role of RAGE and glyoxalase 1. Further we also discuss the crosstalk between glycative stress and ER stress in their effect on protein homeostasis. PMID- 27270768 TI - New efforts to design better tools to track autism therapy response. PMID- 27270766 TI - Diabetic kidney disease: a role for advanced glycation end-product receptor 1 (AGE-R1)? AB - Diabetic patients are postulated to be in a perpetual state of oxidative stress and inflammation at sites where chronic complications occur. The accumulation of AGEs derived from both endogenous and exogenous sources (such as the diet) have been implicated in the development and progression of diabetic complications, particularly nephropathy. There has been some interest in investigating the potential for reducing the AGE burden in chronic disease, through the action of AGE "clearance" receptors, such as the advanced glycation end-product receptor 1 (AGE-R1). Reducing the burden of AGEs has been linked to attenuation of inflammation, slower progression of diabetic complications (in particular vascular and renal complications) and has been shown to extend lifespan. To date, however, there have been no direct investigations into whether AGE-R1 has any role in modulating normal kidney function, or specifically during the development and progression of diabetes. This mini-review will focus on the recent advances in knowledge around the mechanistic function of AGE-R1 and the implications of this for the pathogenesis of diabetic kidney disease. PMID- 27270769 TI - Overtime under the microscope: Universities prep for impact of new labor rule on labs. PMID- 27270771 TI - Use the Bayh-Dole Act to lower drug prices for government healthcare programs. PMID- 27270772 TI - Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status. PMID- 27270773 TI - Reply to "Uveal melanoma cells are resistant to EZH2 inhibition regardless of BAP1 status". PMID- 27270774 TI - HIV-1 immune evasion-a threat to effective vaccines? PMID- 27270775 TI - Regulating inflammation with microbial metabolites. PMID- 27270776 TI - From schizophrenia risk locus to schizophrenia genes. PMID- 27270777 TI - Fatty acid metabolism-the first trigger for cachexia? PMID- 27270778 TI - Corrigendum: Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1. PMID- 27270779 TI - Erratum: Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins. PMID- 27270780 TI - Corrigendum: ROR-gamma drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. PMID- 27270782 TI - Interdisciplinary perspectives on dose limits in radioactive waste management. A research paper developed within the ENTRIA project. AB - Within the ENTRIA project, an interdisciplinary group of scientists developed a research paper3 aiming at a synthesis of the technical, sociology of knowledge, legal, societal, and political aspects of dose limits within the field of radioactive waste management. In this paper, the ENTRIA project is briefly introduced and the work on dose limits is put into the perspective of this much larger project. Selected aspects of the ENTRIA work on dose limits related to the different roles such limits play for different actors as well as to the specific case of nuclear waste disposal are presented. The work recognizes that such limits are indispensable for technological developments and legal security but, at the same time, depend on country and project specific circumstances. This may result in serious conflicts and concerns in public debates as well as in the political realm. In order to better understand the interaction and interdependencies of these various contexts in which debates about dose limits play out, future interdisciplinary research is needed. This research should contribute to an open discourse on dose limits which reflects underlying values, objectives, actors and procedures that have defined present dose limit regimes. Additionally, this research should indicate paths for potential alternatives and complements to these established regimes. PMID- 27270781 TI - Corrigendum: Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. PMID- 27270783 TI - Madura foot caused by Gordonia terrae misdiagnosed as Nocardia. AB - Actinomycetomas are soft tissue bacterial infections that are in the differential for unusual masses of the extremities. Typical infectious agents include Actinomyces and Nocardia and are treated with long-term antibiotics. We report a rare case of Gordonia actinomycetoma that was misdiagnosed as Nocardia and subsequently required surgical excision in addition to antibiotic therapy. PMID- 27270785 TI - Comparison of minute distribution frequency for anesthesia start and end times from an anesthesia information management system and paper records. AB - Use of an anesthesia information management system (AIMS) has been reported to improve accuracy of recorded information. We tested the hypothesis that analyzing the distribution of times charted on paper and computerized records could reveal possible rounding errors, and that this effect could be modulated by differences in the user interface for documenting certain event times with an AIMS. We compared the frequency distribution of start and end times for anesthesia cases completed with paper records and an AIMS. Paper anesthesia records had significantly more times ending with "0" and "5" compared to those from the AIMS (p < 0.001). For case start times, AIMS still exhibited end-digit preference, with times whose last digits had significantly higher frequencies of "0" and "5" than other integers. This effect, however, was attenuated compared to that for paper anesthesia records. For case end times, the distribution of minutes recorded with AIMS was almost evenly distributed, unlike those from paper records that still showed significant end-digit preference. The accuracy of anesthesia case start times and case end times, as inferred by statistical analysis of the distribution of the times, is enhanced with the use of an AIMS. Furthermore, the differences in AIMS user interface for documenting case start and case end times likely affects the degree of end-digit preference, and likely accuracy, of those times. PMID- 27270784 TI - Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with ABCB1 polymorphism. AB - Crizotinib is a standard treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC). We undertook this study to investigate the pharmacokinetics of crizotinib and clinical and pharmacogenomic factors that may increase the risk of adverse events (AEs). We defined clinically significant AEs as grade 4 hematological toxicity, grade >=3 non-hematological toxicity, and any grade of interstitial lung disease. Eight subjects with ALK-positive NSCLC scheduled to receive crizotinib 250 mg twice daily were studied. Six patients were female and two were male, and most of the patients had low body weight with a median body weight of 46.8 kg (range, 42.4-61.0 kg). All patients developed AEs, five developing six clinically significant AEs. Six patients required dose reduction. In pharmacokinetic analysis, blood samples were obtained on days 1 and 15. The mean area under the plasma concentration-time curve from 0-12 h (AUC0-12 ) on day 15 was significantly increased in patients with clinically significant AEs (n = 5) compared with those without (n = 3) (P = 0.04). Genetic polymorphisms of ABCB1 were analyzed. One patient with the ABCB1 1236TT-2677TT-3435TT genotype was an outlier, with an AUC0-12 and peak concentrations on day 15 of 2.84* and 2.61* the mean, respectively, compared with those with other genotypes. Our results suggest that some Japanese NSCLC patients treated with crizotinib developed clinically significant toxicities that were related to altered pharmacokinetics parameters due to genotype and body weight factors. PMID- 27270787 TI - Severe Polyethylene Wear Requiring Revision Total Hip Arthroplasty in Three Dogs. AB - OBJECTIVE: To describe the occurrence of severe polyethylene wear of the acetabular component in 3 dogs that ultimately led to implant failure, and to report the outcome of revision of total hip arthroplasty (THA) in these cases. STUDY DESIGN: Case report ANIMALS: Dogs (n=3). RESULTS: Three dogs with hip dysplasia underwent routine THA before 2 years of age. All dogs became acutely lame 4-5 years after THA. Radiographs revealed acetabular cup wear in all cases, shell fragmentation in 2 cases, and additional stem failure in 1 case. All dogs underwent successful revision surgery, during which severe polyethylene wear and metallosis was observed. Revision surgery provided an excellent clinical outcome in all dogs from 10 months to 4 years post revision. CONCLUSION: Polyethylene wear and implant failure may be a significant long-term complication of THA not previously recognized, which may be especially true when placed at an early age in a large breed, active dog, or in a dog with significant morbidity associated with other limbs. A successful revision was achieved in all 3 dogs. Additional investigation is warranted to document the risk factors associated with severe polyethylene wear in canine THA. PMID- 27270786 TI - TP53 mutations are early events in chronic lymphocytic leukemia disease progression and precede evolution to complex karyotypes. AB - TP53 abnormalities lead to resistance to purine analogues and are found in over 40% of patients with refractory chronic lymphocytic leukemia (CLL). At diagnosis, no more than 5% of patients carry the 17p deletion, most cases harbour mutations within the other TP53 allele. The incidence of a TP53 mutation as the only alteration is approximately 5%, but this depends on the sensitivity of the technique. Recently, having a complex karyotype has been considered a strong adverse prognostic factor. However, there are no longitudinal studies simultaneously examining the presence of the 17p deletion, TP53 mutations and karyotype abnormalities. We conducted a retrospective longitudinal study of 31 relapsed/refractory CLL patients. Two to six blood samples per patient were analyzed, with a median follow-up of 8 years. In this report, we assessed the sequence of events of TP53 clonal evolution and correlated the presence of TP53 abnormalities to genetic instability during progression and treatment. Next generation sequencing allowed the early detection of TP53 mutated clones and was able to be performed on a routine basis, demonstrating an excellent correlation between the Illumina and Ion Torrent technologies. We concluded that TP53 mutations are early events and precede clonal evolution to complex karyotypes. We strongly recommend the early and iterated detection of TP53 mutations in progressive cases. PMID- 27270789 TI - Are the basal ganglia actually controlling movement or quite the opposite? PMID- 27270788 TI - Cascade degradation of organic matters in brewery wastewater using a continuous stirred microbial electrochemical reactor and analysis of microbial communities. AB - A continuous stirred microbial electrochemical reactor (CSMER), comprising of a complete mixing zone (CMZ) and microbial electrochemical zone (MEZ), was used for brewery wastewater treatment. The system realized 75.4 +/- 5.7% of TCOD and 64.9 +/- 4.9% of TSS when fed with brewery wastewater concomitantly achieving an average maximum power density of 304 +/- 31 m W m(-2). Cascade utilization of organic matters made the CSMER remove a wider range of substrates compared with a continuous stirred tank reactor (CSTR), in which process 79.1 +/- 5.6% of soluble protein and 86.6 +/- 2.2% of soluble carbohydrates were degraded by anaerobic digestion in the CMZ and short-chain volatile fatty acids were further decomposed and generated current in the MEZ. Co-existence of fermentative bacteria (Clostridium and Bacteroides, 19.7% and 5.0%), acetogenic bacteria (Syntrophobacter, 20.8%), methanogenic archaea (Methanosaeta and Methanobacterium, 40.3% and 38.4%) and exoelectrogens (Geobacter, 12.4%) as well as a clear spatial distribution and syntrophic interaction among them contributed to the cascade degradation process in CSMER. The CSMER shows great promise for practical wastewater treatment application due to high pre-hydrolysis and acidification rate, high energy recovery and low capital cost. PMID- 27270816 TI - Two-point particle tracking microrheology of nematic complex fluids. AB - Many biological and technological complex fluids exhibit tight microstructural alignment that confers them nematic mechanical properties. Among these we count liquid crystals and biopolymer networks, which are often available in microscopic amounts. However, current microrheological methods cannot measure the directional viscoelastic coefficients that appear in the constitutive relation of nematic complex fluids. This article presents directional two-point particle-tracking microrheology (D2PTM) - a novel microrheology technique to determine these coefficients. We establish the theoretical foundation for D2PTM by analyzing the motion of a probing microscopic particle embedded in a nematic complex fluid, and the mutual hydrodynamic interactions between pairs of distant particles. From this analysis, we generalize the formulation of two-point particle tracking microrheology for nematic complex fluids, and demonstrate that the new formulation provides sufficient information to fully characterize the anisotropic viscoelastic coefficients of such materials. We test D2PTM by simulating the Brownian motion of particles in nematic viscoelastic fluids with prescribed directional frequency-dependent shear moduli, showing that D2PTM accurately recovers the prescribed shear moduli. Furthermore, we experimentally validate D2PTM by applying it to a lyotropic nematic liquid crystal, and demonstrate that this new microrheology method provides results in agreement with dynamic light scattering measurements. Lastly, we illustrate the experimental application of the new technique to characterize nematic F-actin solutions. These experiments constitute the first microrheological measurement of the directional viscoelastic coefficients of an anisotropic soft material. PMID- 27270790 TI - The morphogen Decapentaplegic employs a two-tier mechanism to activate target retinal determining genes during ectopic eye formation in Drosophila. AB - Understanding the role of morphogen in activating its target genes, otherwise epigenetically repressed, during change in cell fate specification is a very fascinating yet relatively unexplored domain. Our in vivo loss-of-function genetic analyses reveal that specifically during ectopic eye formation, the morphogen Decapentaplegic (Dpp), in conjunction with the canonical signaling responsible for transcriptional activation of retinal determining (RD) genes, triggers another signaling cascade. Involving dTak1 and JNK, this pathway down regulates the expression of polycomb group of genes to do away with their repressive role on RD genes. Upon genetic inactivation of members of this newly identified pathway, the canonical Dpp signaling fails to trigger RD gene expression beyond a threshold, critical for ectopic photoreceptor differentiation. Moreover, the drop in ectopic RD gene expression and subsequent reduction in ectopic photoreceptor differentiation resulting from inactivation of dTak1 can be rescued by down-regulating the expression of polycomb group of genes. Our results unravel an otherwise unknown role of morphogen in coordinating simultaneous transcriptional activation and de-repression of target genes implicating its importance in cellular plasticity. PMID- 27270827 TI - Cartilage-hair hypoplasia associated with isolated hypoganglionosis: A case report. AB - Cartilage-hair hypoplasia is a rare metaphyseal chondrodysplasia characterized by diverse clinical manifestations and a high incidence of Hirschsprung disease. We present a male patient with cartilage-hair hypoplasia associated with severe intestinal obstruction. Genetic analysis of ribonuclease mitochondrial RNA processing complex gene identified compound heterozygous mutations consisted with previously reported mutations: n.-14_3dupGAAGCTGAGGACGTGGT and n.183G > T. First, we considered that intestinal obstruction was due to an extensive type of Hirschsprung disease, but it was later confirmed as isolated hypoganglionosis. Isolated hypoganglionosis is rare and its therapeutic strategies are not well established. In cases of cartilage-hair hypoplasia associated with severe intestinal obstruction, the differential diagnosis of not only Hirschsprung disease, but also isolated hypoganglionosis, should be considered. PMID- 27270828 TI - Interaction of Target Oxygen Saturation, Bronchopulmonary Dysplasia, and Pulmonary Hypertension in Small for Gestational Age Preterm Neonates. PMID- 27270829 TI - Development of an advance care planning paradigm for advanced cancer: person centered oncologic care and choices (P-COCC). PMID- 27270830 TI - Ripples on rolandic spikes: A marker of epilepsy severity. AB - OBJECTIVE: Children with rolandic spikes may or may not have seizures, ranging from benign rolandic epilepsy to severe atypical rolandic epilepsy. We investigated whether ripples (80-250 Hz), superimposed on rolandic spikes in surface electroencephalography (EEG), can differentiate between different entities. METHODS: In this cohort study we analyzed the EEG studies of children with rolandic spikes without other EEG or magnetic resonance imaging (MRI) abnormalities. They were divided into the following three groups: (1) rolandic spikes but no epilepsy, (2) typical rolandic epilepsy, and (3) atypical and symptomatic rolandic epilepsy. Ripples superimposed on rolandic spikes were marked in 10 minutes of EEG, and compared to the number of seizures before the EEG. Receiver operating characteristic (ROC) curves were constructed to determine the predictive value of ripples and spikes for having epilepsy (groups 2 and 3) and for differentiating benign courses (groups 1 or 2) from atypical and symptomatic epilepsy (group 3). Ripples were also marked in the time frequency spectrum of averaged rolandic spikes. RESULTS: Ripples were found in 13 of 22 children. Children without epilepsy showed no ripples, except for a single child with only one ripple. The number of ripples showed a significant positive correlation with the number of seizures (rho = 0.70, p = 0.001), whereas spikes had a borderline significant correlation (rho = 0.43, p = 0.05). Presence of more than two ripples was a predictor for having seizures (area under the curve [AUC] 0.84), whereas spikes could not predict having seizures (AUC 0.53). More than five ripples predicted the difference between benign courses and atypical and symptomatic epilepsy (AUC 0.91, sensitivity 63%, specificity 100%). Ripples in the time frequency spectra appeared in all children and were not related to seizures. SIGNIFICANCE: Absence of ripples on top of rolandic spikes predicts a relative benign clinical entity, whereas in the presence of several ripples, the child is likely to have more seizures than classical rolandic epilepsy, and pharmacologic treatment might be needed. PMID- 27270831 TI - Evaluation of Clinical Pharmacists' Interventions in the Czech Republic. AB - STUDY OBJECTIVES: To determine the frequency of interventions, categorized by type of intervention and therapeutic class, made by a team of four clinical pharmacists over a 1-year period, and to assess the potential economic impact of these interventions. DESIGN: Prospective analysis. SETTING: Large medical center in Prague, Czech Republic. PATIENTS: A total of 9153 adults who were admitted to the general surgery, infectious diseases, oncology, orthopedics, and thoracic surgery and respiratory medicine services between January 1, 2014, and December 31, 2014. INTERVENTION: Four clinical pharmacists reviewed patients' medication profiles, participated in medical and surgical rounds, and made drug therapy related recommendations to physicians. MEASUREMENTS AND MAIN RESULTS: Clinical pharmacists' interventions were categorized by therapeutic class and divided into eight types: introduction of a drug, discontinuation of a drug, dosage change, route of administration change, recommendation to continue therapy, recommendation to perform further evaluation (e.g., laboratory assessment), reintroduction of a missing medication, and therapeutic drug monitoring (request to measure a drug concentration and provide its interpretation). All interventions accepted by the attending physicians were recorded by using a software application. For the evaluation of the economic impact of the interventions, published statistical data were used from the Institute of Health Information and Statistics of the Czech Republic. During the 1-year period, the clinical pharmacists performed 1916 interventions. The most frequent intervention was drug discontinuation (27.9% of all interventions), and the drug category with the highest frequency of interventions was central nervous system drugs (25.1%). All interventions were accepted by the physicians. For the evaluation of potential economic impact, a select group of drugs was used, representing 14.4% of the interventions. The benefit:cost ratio was 3:1. CONCLUSION: All interventions made by clinical pharmacists were accepted by the physicians. Drug discontinuation was the most frequent intervention. The analysis of potential economic savings showed the positive impact of these interventions, with a benefit:cost ratio of 3:1. PMID- 27270834 TI - Association of androgen with gender difference in serum adipocyte fatty acid binding protein levels. AB - Clinical investigations have indicated women have higher levels of adipocyte fatty acid binding protein (A-FABP) than men. The present study aimed to identify factors related to gender difference in serum A-FABP levels. A total of 507 participants (194 men, 132 premenopausal women, and 181 postmenopausal women) were enrolled in the present study. Serum A-FABP levels increased in the order from men to premenopausal women to postmenopausal women in both body mass index categories (<25.0 and >=25.0 kg/m(2); all P < 0.05). Multiple stepwise regression analyses showed that after adjustment for factors related to serum A-FABP levels, the trunk fat mass was an independent and positive factor of serum A-FABP levels. For men, total testosterone was associated independently and inversely with serum A-FABP levels. For pre- and postmenopausal women, bioavailable testosterone and total testosterone were independent and positive factors associated with serum A FABP levels, respectively. The present study demonstrated that the androgen was correlated with the serum A-FABP levels negatively in men, but positively in women. With these effects on the fat content, especially trunk fat, androgen might contribute to the gender difference in serum A-FABP levels. PMID- 27270836 TI - Biomimetic heterogeneous multiple ion channels: a honeycomb structure composite film generated by breath figures. AB - We design a novel type of artificial multiple nanochannel system with remarkable ion rectification behavior via a facile breath figure (BF) method. Notably, even though the charge polarity in the channel wall reverses under different pH values, this nanofluidic device displays the same ionic rectification direction. Compared with traditional nanochannels, this composite multiple ion channel device can be more easily obtained and has directional ionic rectification advantages, which can be applied in many fields. PMID- 27270835 TI - CdGAP/ARHGAP31, a Cdc42/Rac1 GTPase regulator, is critical for vascular development and VEGF-mediated angiogenesis. AB - Mutations in the CdGAP/ARHGAP31 gene, which encodes a GTPase-activating protein for Rac1 and Cdc42, have been reported causative in the Adams-Oliver developmental syndrome often associated with vascular defects. However, despite its abundant expression in endothelial cells, CdGAP function in the vasculature remains unknown. Here, we show that vascular development is impaired in CdGAP deficient mouse embryos at E15.5. This is associated with superficial vessel defects and subcutaneous edema, resulting in 44% embryonic/perinatal lethality. VEGF-driven angiogenesis is defective in CdGAP(-/-) mice, showing reduced capillary sprouting from aortic ring explants. Similarly, VEGF-dependent endothelial cell migration and capillary formation are inhibited upon CdGAP knockdown. Mechanistically, CdGAP associates with VEGF receptor-2 and controls VEGF-dependent signaling. Consequently, CdGAP depletion results in impaired VEGF mediated Rac1 activation and reduced phosphorylation of critical intracellular mediators including Gab1, Akt, PLCgamma and SHP2. These findings are the first to demonstrate the importance of CdGAP in embryonic vascular development and VEGF induced signaling, and highlight CdGAP as a potential therapeutic target to treat pathological angiogenesis and vascular dysfunction. PMID- 27270837 TI - Unexpected mitochondrial matrix localization of Parkinson's disease-related DJ-1 mutants but not wild-type DJ-1. AB - DJ-1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ-1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ-1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ-1 is still controversial. Here, we show the mitochondrial matrix localization of various pathogenic and artificial DJ-1 mutants by multiple independent experimental approaches including cellular fractionation, proteinase K protection assays, and specific immunocytochemistry. Localization of various DJ-1 mutants to the matrix is dependent on the membrane potential and translocase activity in both the outer and the inner membranes. Nevertheless, DJ-1 possesses neither an amino-terminal alpha-helix nor a predictable matrix-targeting signal, and a post-translocation processing-derived molecular weight change is not observed. In fact, wild-type DJ-1 does not show any evidence of mitochondrial localization at all. Such a mode of matrix localization of DJ-1 is difficult to explain by conventional mechanisms and implies a unique matrix import mechanism for DJ-1 mutants. PMID- 27270839 TI - Mechanisms of hyperventilation-induced lung injuries in neonatal rats. AB - BACKGROUND: The aim of this study was to investigate the mechanism of early inflammatory injury in neonatal ventilator-induced lung injuries (VILI). METHODS: Newborn rats were randomly assigned to groups and administrated mechanical ventilation with different tidal volumes. Morphological changes in lung tissues were observed, and the levels of interleukin-6 (IL-6), cysteinyl leukotriene mRNA (CysLT1 mRNA), and nuclear factor-kappaB mRNA (NF-kappaBp65 mRNA) in lung tissues were analyzed. RESULTS: The ventilation groups exhibited different degrees of inflammatory cell infiltration, which was aggravated as the tidal volume and ventilation time increased. The IL-6 levels of the hyperventilation 5H, conventional ventilation 5H, hyperventilation 3H, control, and normal lung-tissue group were 785.33 +/- 39.06, 701.6 +/- 33.65, 686.65 +/- 46.85, 637.63 +/- 40.55, and 635.02 +/- 65.78 pg/g, respectively. Hyperventilation increased the levels of IL-6 and NF-kappaBp65 mRNAas the ventilation time increased, and IL-6 was positively correlated with NF-kappaBp65 mRNA levels (r = 0.72, P < 0.01). Longer hyperventilation periods upregulate the level of CysLT1 mRNA. CysLT1 mRNA/GAPDH of the hyperventilation 5H group was 2.14 +/- 1.45 (P < 0.01). CONCLUSIONS: Mechanical ventilation with a large tidal volume can cause VILI, characterized at an early stage by inflammatory responses and particularly by the increased secretion and invasion of inflammatory cytokines and inflammatory cells. The activation of the NF-kappaB-IL-6 signaling pathway was an important mechanism for the initiation of VILI. Additionally, CysLT1 was involved in the inflammatory VILI damage, and its upregulation occurred later than that of IL-6. PMID- 27270838 TI - Association of the AURKA and AURKC gene polymorphisms with an increased risk of gastric cancer. AB - Single nucleotide polymorphisms (SNPs) in mitotic checkpoint genes can contribute to susceptibility of human cancer, including gastric cancer (GC). We aimed to investigate the effects of Aurora kinase A (AURKA), Aurora kinase B (AURKB), and Aurora kinase C (AURKC) gene polymorphisms on GC risk in Slovenian population. We genotyped four SNPs in AURKA (rs2273535 and rs1047972), AURKB (rs2241909), and AURKC (rs758099) in a total of 128 GC patients and 372 healthy controls using TaqMan allelic discrimination assays to evaluate their effects on GC risk. Our results showed that genotype frequencies between cases and controls were significantly different for rs1047972 and rs758099 (P < 0.05). Our study demonstrated that AURKA rs1047972 TT and (CC + CT) genotypes were significantly associated with an increased risk of gastric cancer. Our results additionally revealed that AURKC rs758099 TT and (CC + CT) genotypes were also associated with increased GC risk. In stratified analysis, genotypes TT and (CC + CT) of AURKA rs1047972 SNP were associated with increased risk of both, intestinal and diffuse, types of GC. In addition, AURKC rs758099 TT and (CC + CT) genotypes were positively associated with increased intestinal type GC risk, but not with an increased diffuse type GC risk. Based on these results, we can conclude that AURKA rs1047972 and AURKC rs758099 polymorphisms could affect the risk of GC development. Further larger studies are needed to confirm these findings. (c) 2016 IUBMB Life, 68(8):634-644, 2016. PMID- 27270840 TI - Formation of a Double Diamond Cubic Phase by Thermotropic Liquid Crystalline Self Assembly of Bundled Bolaamphiphiles. AB - A quaternary amphiphile with swallow-tail side groups displays a new bicontinuous thermotropic cubic phase with symmetry Pn3? m and formed by two interpenetrating networks where cylindrical segments are linked by H bonds at tetrahedral junctions. Each network segment contains two bundles, each containing 12 rod-like mesogens, lying along the segment axis. This assembly leads to the first thermotropic structure of the "double diamond" type. A quantitative geometric model is proposed to explain the occurrence of this rare phase. PMID- 27270842 TI - Sustaining Health Care Interventions to Achieve Quality Care: What We Can Learn From Rapid Response Teams. AB - Rapid response team (RRT) adoption and implementation are associated with improved quality of care of patients who experience an unanticipated medical emergency. The sustainability of RRTs is vital to achieve long-term benefits of these teams for patients, staff, and hospitals. Factors required to achieve RRT sustainability remain unclear. This study examined the relationship between sustainability elements and RRT sustainability in hospitals that have previously implemented RRTs. PMID- 27270841 TI - Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans. AB - KEY POINTS: A recent 30 year prospective study showed that lifelong sauna use reduces cardiovascular-related and all-cause mortality; however, the specific cardiovascular adaptations that cause this chronic protection are currently unknown. We investigated the effects of 8 weeks of repeated hot water immersion ('heat therapy') on various biomarkers of cardiovascular health in young, sedentary humans. We showed that, relative to a sham group which participated in thermoneutral water immersion, heat therapy increased flow-mediated dilatation, reduced arterial stiffness, reduced mean arterial and diastolic blood pressure, and reduced carotid intima media thickness, with changes all on par or greater than what is typically observed in sedentary subjects with exercise training. Our results show for the first time that heat therapy has widespread and robust effects on vascular function, and as such, could be a viable treatment option for improving cardiovascular health in a variety of patient populations, particularly those with limited exercise tolerance and/or capabilities. ABSTRACT: The majority of cardiovascular diseases are characterized by disorders of the arteries, predominantly caused by endothelial dysfunction and arterial stiffening. Intermittent hot water immersion ('heat therapy') results in elevations in core temperature and changes in cardiovascular haemodynamics, such as cardiac output and vascular shear stress, that are similar to exercise, and thus may provide an alternative means of improving health which could be utilized by patients with low exercise tolerance and/or capabilities. We sought to comprehensively assess the effects of 8 weeks of heat therapy on biomarkers of vascular function in young, sedentary subjects. Twenty young, sedentary subjects were assigned to participate in 8 weeks (4-5 times per week) of heat therapy (n = 10; immersion in a 40.5 degrees C bath sufficient to maintain rectal temperature >= 38.5 degrees C for 60 min per session) or thermoneutral water immersion (n = 10; sham). Eight weeks of heat therapy increased flow-mediated dilatation from 5.6 +/- 0.3 to 10.9 +/- 1.0% (P < 0.01) and superficial femoral dynamic arterial compliance from 0.06 +/- 0.01 to 0.09 +/-0.01 mm(2) mmHg(-1) (P = 0.03), and reduced (i.e. improved) aortic pulse wave velocity from 7.1 +/- 0.3 to 6.1 +/- 0.3 m s(-1) (P = 0.03), carotid intima media thickness from 0.43 +/- 0.01 to 0.37 +/- 0.01 mm (P < 0.001), and mean arterial blood pressure from 83 +/- 1 to 78 +/- 2 mmHg (P = 0.02). No changes were observed in the sham group or for carotid arterial compliance, superficial femoral intima media thickness or endothelium-independent dilatation. Heat therapy improved endothelium-dependent dilatation, arterial stiffness, intima media thickness and blood pressure, indicating improved cardiovascular health. These data suggest heat therapy may provide a simple and effective tool for improving cardiovascular health in various populations. PMID- 27270843 TI - Predicting Sepsis Risk Using the "Sniffer" Algorithm in the Electronic Medical Record. AB - The Sepsis "Sniffer" Algorithm (SSA) has merit as a digital sepsis alert but should be considered an adjunct to versus an alternative for the Nurse Screening Tool (NST), given lower specificity and positive predictive value. The SSA reduced the risk of incorrectly categorizing patients at low risk for sepsis, detected sepsis high risk in half the time, and reduced redundant NST screens by 70% and manual screening hours by 64% to 72%. Preserving nurse hours expended on manual sepsis alerts may translate into time directed toward other patient priorities. PMID- 27270845 TI - CMS Nonpayment Policy, Quality Improvement, and Hospital-Acquired Conditions: An Integrative Review. AB - This integrative review synthesized evidence on the consequences of the Centers for Medicare & Medicaid Services (CMS) nonpayment policy on quality improvement initiatives and hospital-acquired conditions. Fourteen articles were included. This review presents strong evidence that the CMS policy has spurred quality improvement initiatives; however, the relationships between the CMS policy and hospital-acquired conditions are inconclusive. In future research, a comprehensive model of implementation of the CMS nonpayment policy would help us understand the effectiveness of this policy. PMID- 27270844 TI - Critical Access Hospital Use of TeamSTEPPS to Implement Shift-Change Handoff Communication. AB - Implementation of handoff as part of TeamSTEPPS initiatives for improving shift change communication is examined via qualitative analysis of on-site interviews and process observations in 8 critical access hospitals. Comparing implementation attributes and handoff performance across hospitals shows that the purpose of implementation did not differentiate between high and low performance, but facilitators and barriers did. Staff involvement and being part of the "big picture" were important facilitators to change management and buy-in. PMID- 27270846 TI - Patients' Perceptions of Bedside Handoff: Further Evidence to Support a Culture of Always. AB - Patients' perceptions of satisfaction, understanding, participation, and feelings of safety were significantly correlated with the frequency of bedside handoff. Mean responses to survey items in these areas were significantly higher for patients who "always" experienced bedside handoff than for those who experienced it sporadically. Quality improvement strategies were effective in increasing the frequency of bedside handoff. PMID- 27270848 TI - Time-Out and Checklists: A Survey of Rural and Urban Operating Room Personnel. AB - Surgical safety checklists were introduced to improve patient safety. Urban and rural hospitals are influenced by differing factors, but how these factors affect patient care is unknown. This study examined time-out and checklist processes in rural and urban operating rooms and found that although checklist use has been adopted in many organizations, use is inconsistent across both settings. An understanding of these variations is needed to improve utilization. PMID- 27270847 TI - Evaluation of the Multimodal Strategy for Improvement of Hand Hygiene as Proposed by the World Health Organization. AB - Hand hygiene has the biggest impact and is the least expensive way to prevent and control health care-associated infections. In this study, we assessed the effectiveness of the multimodal strategy of the World Health Organization to improve health care-associated infection rates, hand hygiene compliance, and the related knowledge of health care professionals in a Brazilian university hospital. We observed the necessity for an alternative approach in hospitals with high staff turnover and low attendance of educational sessions. PMID- 27270849 TI - Staff perceptions of barriers to physical restraint-reduction in long-term care: a meta-synthesis. AB - AIMS AND OBJECTIVES: To critically review the existing qualitative studies to identify, from the perspective of staff, the barriers to physical restraint reduction in long-term geriatric care facilities. BACKGROUND: Despite the adverse physical and psychosocial effects, physical restraints are still used frequently in many geriatric long-term care facilities around the world. There is, however, no study that synthesises the existing qualitative literature regarding the barriers to the restraint reduction from the perspective of facility staff. DESIGN/METHODS: The metastudy research process guided this qualitative synthesis. Five electronic databases were searched, and ten studies were included in this metastudy. RESULTS: Five themes were identified through metasynthesis of the findings: concern about and responsibility for safety, unclear and inconsistent definitions of restraint and restraint-free care, difficulties in the transition from acceptance to removal, noninvolvement in decision-making to remove restraint and insufficient resources and education. CONCLUSION: A concept analysis of physical restraint is sorely needed, and future studies should explore the prevalence of restraint, the effects of education for staff and family on restraint reduction, and success stories related to restraint-free care. More research is needed regarding the restraint reduction effectiveness and cost issues. RELEVANCE TO CLINICAL PRACTICE: Physical restraints, commonly used in many geriatric long-term care facilities, result in many negative effects and ethical issues. To achieve success in reducing physical restraint use, governmental policies and long-term care institutions should underpin staff efforts with legal, educational and practical support. PMID- 27270850 TI - Health status and treatment-seeking stigma in older adults with trauma and posttraumatic stress disorder. AB - This study compared health status across four trauma/posttraumatic stress disorder (PTSD) groups of older adults with depression, anxiety, and/or at-risk drinking who attended primary care appointments (N = 1,199; mean age = 73.5 yr), mostly at Department of Veterans Affairs hospitals. The trauma and PTSD categories were PTSD (n = 81), partial PTSD (n = 127), trauma only (n = 323), and no trauma (n = 668). Physical and mental health-related quality of life (HQL), indices of social and economic impairment and stigma regarding treatment-seeking were compared among groups. Group differences were found for several indicators of functional impairment; the PTSD group had fewer close friends and higher treatment-seeking stigma beliefs related to having a disorder. Linear mixed modeling examined associations between trauma/PTSD group and HQL. After accounting for covariates, the trauma/PTSD groups differed across the Medical Outcome Study Short Form-36 scales and component scores (indicated by significant group by scale interaction). Differences among groups were confined to mental health measures; those with PTSD had worse HQL. Post hoc analyses examined the number of comorbid psychiatric diagnoses by trauma/PTSD group. Overall, findings indicate that mental HQL varies among older adults with trauma and PTSD and that although treatment-related stigma does not differ among groups, it does affect HQL. PMID- 27270851 TI - RE: The AAST AORTA registry and data on REBOA. PMID- 27270852 TI - The AAST AORTA registry and data on REBOA. PMID- 27270853 TI - Home safe home: Evaluation of a childhood home safety program. AB - BACKGROUND: The London Health Sciences Centre Home Safety Program (HSP) provides safety devices, education, a safety video, and home safety checklist to all first time parents for the reduction of childhood home injuries. The objective of this study was to evaluate the HSP for the prevention of home injuries in children up to 2 years of age. METHODS: A program evaluation was performed with follow-up survey, along with an interrupted time series analysis of emergency department (ED) visits for home injuries 5 years before (2007-2013) and 2 years after (2013 2015) implementation. Spatial analysis of ED visits was undertaken to assess differences in home injury rates by dissemination areas controlling differences in socioeconomic status (i.e., income, education, and lone-parent status) at the neighborhood level. RESULTS: A total of 3,458 first-time parents participated in the HSP (a 74% compliance rate). Of these, 20% (n = 696) of parents responded to our questionnaire, with 94% reporting the program to be useful (median, 6; interquartile range, 2 on a 7-point Likert scale) and 81% learning new strategies for preventing home injuries. The median age of the respondent's babies were 12 months (interquartile range, 1). The home safety check list was used by 87% of respondents to identify hazards in their home, with 95% taking action to minimize the risk. The time series analysis demonstrated a significant decline in ED visits for home injuries in toddlers younger than2 years of age after HSP implementation. The declines in ED visits for home injuries remained significant over and above each socioeconomic status covariate. CONCLUSION: Removing hazards, supervision, and installing safety devices are key facilitators in the reduction of home injuries. Parents found the HSP useful to identify hazards, learn new strategies, build confidence, and provide safety products. Initial finding suggests that the program is effective in reducing home injuries in children up to 2 years of age. LEVEL OF EVIDENCE: Therapeutic/care management study, level V. PMID- 27270854 TI - Posterior paramedian subrhomboidal analgesia versus thoracic epidural analgesia for pain control in patients with multiple rib fractures. AB - BACKGROUND: Rib fractures are common in trauma admissions and are associated with an increased risk of pulmonary complications, intensive care unit admissions, and mortality. Providing adequate pain control in patients with multiple rib fractures decreases the risk of adverse events. Thoracic epidural analgesia is currently the preferred method for pain control. This study compared outcomes in patients with multiple acute rib fractures treated with posterior paramedian subrhomboidal (PoPS) analgesia versus thoracic epidural analgesia (TEA). METHODS: This prospective study included 30 patients with three or more acute rib fractures admitted to a Level I trauma center. Thoracic epidural analgesia or PoPS catheters were placed, and local anesthesia was infused. Data were collected including patients' pain level, adjunct morphine equivalent use, adverse events, length of stay, lung volumes, and discharge disposition. Nonparametric tests were used and two-sided p < 0.05 were considered statistically significant. RESULTS: Nineteen (63%) of 30 patients received TEA and 11 (37%) of 30 patients received PoPS. Pain rating was lower in the PoPS group (2.5 vs. 5; p = 0.03) after initial placement. Overall, there was no other statistically significant difference in pain control or use of oral morphine adjuncts between the groups. Hypotension occurred in eight patients, 75% with TEA and only 25% with PoPS. No difference was found in adverse events, length of stay, lung volumes, or discharge disposition. CONCLUSION: In patients with rib fractures, PoPS analgesia may provide pain control equivalent to TEA while being less invasive and more readily placed by a variety of hospital staff. This pilot study is limited by its small sample size, and therefore additional studies are needed to prove equivalence of PoPS compared to TEA. LEVEL OF EVIDENCE: Therapeutic study, level IV. PMID- 27270855 TI - Design of a cost-effective, hemodynamically adjustable model for resuscitative endovascular balloon occlusion of the aorta (REBOA) simulation. AB - Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct technique for salvaging patients with noncompressible torso hemorrhage. Current REBOA training paradigms require large animals, virtual reality simulators, or human cadavers for acquisition of skills. These training strategies are expensive and resource intensive, which may prevent widespread dissemination of REBOA. We have developed a low-cost, near-physiologic, pulsatile REBOA simulator by connecting an anatomic vascular circuit constructed out of latex and polyvinyl chloride tubing to a commercially available pump. This pulsatile simulator is capable of generating cardiac outputs ranging from 1.7 to 6.8 L/min with corresponding arterial blood pressures of 54 to 226/14 to 121 mmHg. The simulator accommodates a 12 French introducer sheath and a CODA balloon catheter. Upon balloon inflation, the arterial waveform distal to the occlusion flattens, distal pulsation within the simulator is lost, and systolic blood pressures proximal to the balloon catheter increase by up to 62 mmHg. Further development and validation of this simulator will allow for refinement, reduction, and replacement of large animal models, costly virtual reality simulators, and perfused cadavers for training purposes. This will ultimately facilitate the low cost, high-fidelity REBOA simulation needed for the widespread dissemination of this life-saving technique. PMID- 27270856 TI - Defining the cervical spine clearance algorithm: A single-institution prospective study of more than 9,000 patients. AB - BACKGROUND: Variability exists in the approach to cervical spine (c-spine) clearance after significant trauma. Using concurrently gathered data on more than 9,000 such patients, the current study develops an evidence-based and readily adoptable algorithm for c-spine clearance aimed at timely removal of collar, optimal use of imaging, and appropriate spine consultations. METHODS: Prospective study of adult blunt trauma team alert (TTA) patients presenting at a Level I trauma center who underwent screening computed tomography (CT) to diagnose/rule out c-spine injury (January 2008 to May 2014). Regression analysis comparing patients with and without c-spine injury-fracture and/or ligament-was used to identify significant predictors of injury. The predictors with the highest odds ratio were used to develop the algorithm. RESULTS: Among 9,227 patients meeting inclusion criteria, c-spine injury was identified in 553 patients (5.99%). All 553 patients had a c-spine fracture, and of these, 57 patients (0.6% of entire population and 10.31% of patients with injury) also had a ligamentous injury. No patient with a normal CT result was found to have an injury. The five greatest predictors of ligament injury that follow were used to develop the algorithm: (1) CT evidence of ligament injury; (2) fracture pattern "not" isolated transverse/spinous process; (3) neurologic symptoms; (4) midline tenderness; and (5) Glasgow Coma Scale score <15. CONCLUSION: TTA patients should undergo screening c-spine CT to rule out injury. Most patients will have a negative CT and can have their collars removed. A select group of patients will require collars and spine consultation and a smaller subset of magnetic resonance imaging to rule out ligament injury. LEVEL OF EVEDINCE: Therapeutic study, level III. PMID- 27270857 TI - Evaluation of respiratory volume monitoring (RVM) to detect respiratory compromise in advance of pulse oximetry and help minimize false desaturation alarms. AB - BACKGROUND: Monitoring respiratory function is important. By continuously monitoring respiratory volumes, respiratory depression could be identified before hypoxemia and drive earlier intervention. Here, we evaluate the temporal relationship of respiratory volume monitoring (providing real-time minute ventilation [MV], tidal volume, and respiratory rate in nonintubated patients) to hypoxemic episodes and its potential to help classify true vs false desaturations (related to patient movement/probe dislodgement). METHODS: Respiratory volume monitoring data, oxygen saturation (SpO2), oxygen supplementation, and opioid use were analyzed in 259 patients following orthopedic surgery. Detection of "low MV" (<40% of predicted MV) in advance of low SpO2 (<90%) was used to classify true and false desaturations. Patients were also stratified based on opioid use and development of low MV. Patient's length of stay (LOS) and number of SpO2 alarms were compared across groups (+/- opioids; +/- low MV). RESULTS: The electronic health records reported 113 SpO2 alarms; 105 (93%) not preceded by low MV and considered false. Low MV preceded the eight true desaturations by 12.8 +/- 2.8 minutes. One hundred ninety-eight patients (76%) of 259 experienced one or more low MV events. Patients with low MV had significantly longer postanesthesia care unit (PACU) LOS than those maintaining "adequate MV": 2.8 +/- 0.1 hours vs. 2.4 +/- 0.1 hours (p < 0.001). Patients receiving opioids had increased likelihood of low MV (69% vs. 80%; p < 0.05) and had significantly longer PACU LOS than those without opioids (2.9 +/- 0.1 hours vs. 2.3 +/- 0.1 hours; p < 0.001). In the opioid group, PACU LOS was 75% longer in patients developing low MV versus maintaining adequate MV (3.0 +/- 0.1 hours vs. 1.7 +/- 0.2 hours; p < 0.001). CONCLUSION: Respiratory volume monitoring can provide advanced warning of impending oxygen desaturation and potentially reduce the number of false SpO2 alarms. Opioid administration increased low MV events correlating with increased LOS. Respiratory volume monitoring can help clinicians individualize patient care, decrease false alarms, adjust opioid dosing, and increase PACU throughput. Similar benefits may translate to the general care floor and prehospital and posthospital environments. LEVEL OF EVIDENCE: Diagnostic study, level II. PMID- 27270859 TI - Middle-Upper Pleistocene climate changes shaped the divergence and demography of Cycas guizhouensis (Cycadaceae): Evidence from DNA sequences and microsatellite markers. AB - Climatic oscillations in the Pleistocene have had profound effects on the demography and genetic diversity of many extant species. Cycas guizhouensis Lan &R.F. Zou is an endemic and endangered species in Southwest China that is primarily distributed along the valleys of the Nanpan River. In this study, we used four chloroplast DNAs (cpDNA), three nuclear genes (nDNA) and 13 microsatellite (SSR) loci to investigate the genetic structure, divergence time and demographic history of 11 populations of C. guizhouensis. High genetic diversity and high levels of genetic differentiation among the populations were observed. Two evolutionary units were revealed based on network and Structure analysis. The divergence time estimations suggested that haplotypes of C. guizhouensis were diverged during the Middle-Upper Pleistocene. Additionally, the demographic histories deduced from different DNA sequences were discordant, but overall indicated that C. guizhouensis had experienced a recent population expansion during the post-glacial period. Microsatellite data revealed that there was a contraction in effective population size in the past. These genetic features allow conservation measures to be taken to ensure the protection of this endangered species from extinction. PMID- 27270860 TI - Redox-Active Tetraruthenium Macrocycles Built from 1,4-Divinylphenylene-Bridged Diruthenium Complexes. AB - Metallamacrocylic tetraruthenium complexes were generated by treatment of 1,4 divinylphenylene-bridged diruthenium complexes with functionalized 1,3-benzene dicarboxylic acids and characterized by HR ESI-MS and multinuclear NMR spectroscopy. Every divinylphenylene diruthenium subunit is oxidized in two consecutive one-electron steps with half-wave potential splittings in the range of 250 to 330 mV. Additional, smaller redox-splittings between the +/2+ and 0/+ and the 3+/4+ and 2+/3+ redox processes, corresponding to the first and the second oxidations of every divinylphenylene diruthenium entity, are due to electrostatic effects. The lack of electronic coupling through bond or through space is explained by the nodal properties of the relevant molecular orbitals and the lateral side-by-side arrangement of the divinylphenylene linkers. The polyelectrochromic behavior of the divinylphenylene diruthenium precursors is retained and even amplified in these metallamacrocyclic structures. EPR studies down to T=4 K indicate that the dications 1-H(2+) and 1-OBu(2+) are paramagnetic. The dications and the tetracation of macrocycle 3-H display intense (dications) or weak (3-H(4+) ) EPR signals. Quantum chemical calculations indicate that the four most stable conformers of the macrocycles are largely devoid of strain. Bond parameters, energies as well as charge and spin density distributions of model macrocycle 5-H(Me) were calculated for the different charge and spin states. PMID- 27270858 TI - Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder. AB - Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naive patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-alpha, transforming growth factor [TGF]-beta1, interleukin [IL]-6, IL-8 and IL-1beta) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P < 0.001) declined in both groups, the SBP group had significantly lower levels of BDNF (P = 0.005) and TGF beta1 (P = 0.02). Patients with SBP and BP-II respond similarly to treatment, but SBP patients may have different neuroinflammation marker expression. PMID- 27270861 TI - Cryopreservation (-20 degrees C) of feline corneoscleral tissue: histologic, microbiologic, and ultrastructural study. AB - OBJECTIVE: To evaluate microbiological, histologic, and ultrastructural characteristics of short-term cryopreserved (STC) feline corneoscleral tissue (<1 year) and to compare it with long-term cryopreserved (LTC) tissue (>7 years). ANIMALS STUDIED: Twenty healthy feline globes were obtained from 2003 to 2013. PROCEDURE: After a decontamination protocol, globes were enucleated and stored at -20 degrees C in broad-spectrum antibiotics. Corneoscleral tissue was evaluated at different storage periods: <1 year (10 eyes) and >7 years (8 eyes). Two eyes were used as controls. Microbiologic study included direct (blood, McConkey, and Sabouraud agars) and enrichment (brain-heart infusion broth) cultures. Cryopreservation artifacts were evaluated by hematoxylin-eosin. Corneoscleral collagen organization and number of normal and dead keratocytes were established by transmission electron microscopy. RESULTS: Although microbiologic cultures were positive only in STC [direct (20.8%); enrichment (37.5%)], significant differences between periods were only found in enrichment cultures (P = 0.006). Cryopreservation artifacts were most commonly observed in LTC tissues (P < 0.001). Normal keratocytes were predominant in STC corneas (STC 58.3%, LTC 12.5%) and apoptotic ones in LTC (STC 41.7%, LTC 75%), whereas necrotic keratocytes were only seen in LTC (LTC 12.5%) (P = 0.046). No structural differences were detected in collagen organization between STC and LTC (Pcornea = 0.147; Psclera = 0.362). CONCLUSIONS: Cryopreservation of feline corneoscleral tissue seems to reduce bacterial contamination over time. Apoptosis is the main cause of death of cryopreserved feline keratocytes. Based on the lack of significant structural differences between STC and LTC samples, these cryopreserved tissues could potentially be used for tectonic support for at least 10 years without structural or microbiological impediment. PMID- 27270862 TI - Remembering John Herbert Beynon 29th December 1923 to 24th August 2015. PMID- 27270863 TI - Super-atmospheric pressure ionization mass spectrometry and its application to ultrafast online protein digestion analysis. AB - Ion source pressure plays a significant role in the process of ionization and the subsequent ion transmission inside a mass spectrometer. Pressurizing the ion source to a gas pressure greater than atmospheric pressure is a relatively new approach that aims to further improve the performance of atmospheric pressure ionization sources. For example, under a super-atmospheric pressure environment, a stable electrospray can be sustained for liquid with high surface tension such as pure water, because of the suppression of electric discharge. Even for nano electrospray ionization (nano-ESI), which is known to work with aqueous solution, its stability and sensitivity can also be enhanced, particularly in the negative mode when the ion source is pressurized. A brief review on the development of super-atmospheric pressure ion sources, including high-pressure electrospray, field desorption and superheated ESI, and the strategies to interface these ion sources to a mass spectrometer will be given. Using a recent ESI prototype with an operating temperature at 220 degrees C under 27 atm, we also demonstrate that it is possible to achieve an online Asp-specific protein digestion analysis in which the whole processes of digestion, ionization and MS acquisition could be completed on the order of a few seconds. This method is fast, and the reaction can even be monitored on a near-real-time basis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270864 TI - Mapping Dicorynia guianensis Amsh. wood constituents by submicron resolution cluster-TOF-SIMS imaging. AB - The preparation of tropical wood surface sections for time-of-flight secondary ion mass spectrometry imaging is described, and the use of delayed extraction of secondary ions and its interest for the analysis of vegetal surface are shown. The method has been applied to the study by time-of-flight secondary ion mass spectrometry imaging with a resolution of less than one micron of a tropical wood species, Dicorynia guianensis, which is one of the most exploited wood in French Guiana for its durable heartwood. The heartwood of this species exhibits an economical importance, but its production is not controlled in forestry. Results show an increase of tryptamine from the transition zone and a concomitant decrease of inorganic ions and starch fragment ions. These experiments lead to a better understanding of the heartwood formation and the origin of the natural durability of D. guianensis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270865 TI - Surface acoustic wave nebulization device with dual interdigitated transducers improves SAWN-MS performance. AB - We compared mass spectrometric (MS) performance of surface acoustic wave nebulization (SAWN) generated by a single interdigitated transducer (IDT) designed to produce a progressive wave (PW) to one with a dual IDT that can in theory generate standing waves (SW). Given that devices using dual IDTs had been shown to produce fewer large size droplets on average, we hypothesized they would improve MS performance by improving the efficiency of desolvation. Indeed, the SW SAWN chip provided an improved limit of detection of 1 femtomole of peptide placed on chip making it 100* more sensitive than the PW design. However, as measured by high-speed image recording and phase Doppler particle analyzer measurements, there was only a 26% increase in the small diameter (1-10 um) droplets produced from the new device, precluding a conclusion that the decrease in droplet size was solely responsible for the improvement in MS signal/noise. Given that the dual IDT design produced a more instantaneous plume than the PW design, the more likely contributor to improved MS signal/noise was concluded to be a higher ion flux entering the mass spectrometer for the dual IDT designs. Notably, the dual IDT device allowed production of much higher quality protein mass spectra up to about 20 kDa, compared with the single IDT device. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270866 TI - The investigation of the bitumen from ancient Greek amphora using FT ICR MS, H/D exchange and novel spectrum reduction approach. AB - Recently Russian archeologists have discovered on Taman peninsula an ancient (V B.C.) Greek amphora full of dense bitumen. This is the oldest amphora in the world that contains bitumen. We report the investigation of this bitumen using ultrahigh resolution Fourier transform mass spectrometry. Also we used recently developed in-ESI source Hydrogen/Deuterium exchange approach for the structural characterization of the individual molecules and estimation of the biodegradation of the bitumen. The increase of number of the labile hydrogens compared to the non-degraded oil can serve as an additional evidence of the degradation of bitumen via oxidation. For the facilitation of the spectrum processing we have developed the special iterative spectrum reduction approach. It was observed that molecules that have only oxygen heteroatoms possess two -OH groups what is unusual for the petroleum. Based on this we suggested that the bitumen degraded during its being in amphora for 2500 years. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270867 TI - Mass spectrometric approaches for the identification of anthracycline analogs produced by actinobacteria. AB - Anthracyclines are a well-known chemical class produced by actinobacteria used effectively in cancer treatment; however, these compounds are usually produced in few amounts because of being toxic against their producers. In this work, we successfully explored the mass spectrometry versatility to detect 18 anthracyclines in microbial crude extract. From collision-induced dissociation and nuclear magnetic resonance spectra, we proposed structures for five new and identified three more anthracyclines already described in the literature, nocardicyclins A and B and nothramicin. One new compound 8 (4-[4-(dimethylamino) 5-hydroxy-4,6-dimethyloxan-2-yl]oxy-2,5,7,12-tetrahydroxy-3,10-dimethoxy-2-methyl 3,4-dihydrotetracene-1,6,11-trione) was isolated and had its structure confirmed by (1) H nuclear magnetic resonance. The anthracyclines identified in this work show an interesting aminoglycoside, poorly found in natural products, 3-methyl rhodosamine and derivatives. This fact encouraged to develop a focused method to identify compounds with aminoglycosides (rhodosamine, m/z 158; 3-methyl rhodosamine, m/z 172; 4'-O-acethyl-3-C-methyl-rhodosamine, m/z 214). This method allowed the detection of four more anthracyclines. This focused method can also be applied in the search of these aminoglycosides in other microbial crude extracts. Additionally, it was observed that nocardicyclin A, nothramicin and compound 8 were able to interact to DNA through a DNA-binding study by mass spectrometry, showing its potential as anticancer drugs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270868 TI - Nitrogen incorporation in saturated aliphatic C6-C8 hydrocarbons and ethanol in low-pressure nitrogen plasma generated by a hollow cathode discharge ion source. AB - Ion/molecule reactions of saturated hydrocarbons (n-hexane, cyclohexane, n heptane, n-octane and isooctane) in 28-Torr N2 plasma generated by a hollow cathode discharge ion source were investigated using an Orbitrap mass spectrometer. It was found that the ions with [M+14](+) were observed as the major ions (M: sample molecule). The exact mass analysis revealed that the ions are nitrogenated molecules, [M+N](+) formed by the reactions of N3 (+) with M. The reaction, N3 (+) + M -> [M+N](+) + N2 , were examined by the density functional theory calculations. It was found that N3 (+) abstracts the H atom from hydrocarbon molecules leading to the formation of protonated imines in the forms of R'R"C?NH2 (+) (i.e. C-H bond nitrogenation). This result is in accord with the fact that elimination of NH3 is the major channel for MS/MS of [M+N](+) . That is, nitrogen is incorporated in the C-H bonds of saturated hydrocarbons. No nitrogenation was observed for benzene and acetone, which was ascribed to the formation of stable charge-transfer complexes benzene????N3 (+) and acetone????N3 (+) revealed by density functional theory calculations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270869 TI - Simplification of electrospray mass spectra of Polysorbate 80 via cation transfer to carborane anions. AB - Mass spectrometric analysis of polymer mixtures via electrospray ionization can be complicated due the presence of multiple ion types, multiple charge states and multiple oligomeric distributions that complicate the detection and identification of mixture components. Polysorbate 80 (commercially known as Tween((r)) 80) provides an example of this type, where the presence of polyoxyethylene sorbitan monooleate (PSO) byproducts gives rise to overlapping polymer distributions. It is desirable to simplify the spectrum in order to identify each component of what is inherently a complex mixture of fatty esters bound to different head groups. In this work, we show that gas-phase ion/ion reactions with carborane anions allow for the charge reduction of Tween((r)) 80 peaks by selectively removing metal adducts bound to the synthetic polymer. The resulting singly charged spectrum reduces overlapping distributions and thus simplifies the identification of the components found in a Tween((r)) 80 sample. The overall approach described here would likely lead to similar benefits in the analysis of other polymers that tend to ionize via metal ion adduction. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270870 TI - Comment on: MALDI ionization mechanisms investigated by comparison of isomers of dihydroxybenzoic acid. AB - Ionization mechanism of matrix-assisted laser desorption/ionization was recently investigated by Kirmess et al. (J. Mass Spectrom. 2016, 51, 79). The authors compared the ion yields of dihydroxybenzoic acid isomers between experimental measurements and theoretical models and claimed that the predictions of chemical and physical dynamics model are in good agreement with experimental data, but the predictions of thermal model are not. Here, we show that wrong S1-S1 energy pooling rate constants and absorption cross sections were used in the aforementioned article. In addition, we suggest the authors to list the values of many parameters used in their calculations and describe how they obtained these values because these values are completely unknown. PMID- 27270871 TI - Super-atmospheric pressure ionization mass spectrometry and its application to ultrafast online protein digestion analysis. AB - Pressure is a key parameter for an ionization source. In this Special Feature article, Lee Chuin Chen and colleagues review super-atmospheric pressure ionization MS with electrospray, corona-discharge-based chemical ionization, and field desorption. They routinely run their mass spectrometer with ion source pressures ranging from several to several tens of atmospheres. A number of strategies have been used to preserve the high vacuum of the instrument while working with a high-pressure (HP) ion source. A recent prototype uses a booster pump with variable pumping speed added to the first pumping stage of the mass spectrometer to regulate a constant vacuum pressure. Further, a new HP-ESI source allowing rapid (a few seconds) online protein digestion MS is also reported. Dr. Lee Chuin Chen is Associate Professor in the Department of Interdisciplinary Research at the University of Yamanashi (Yamanashi, Japan). His main research interest is the development of novel mass spectrometric methods for in-situ medical diagnosis. PMID- 27270872 TI - Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial. AB - Non-alcoholic fatty liver disease (NAFLD) is a global health problem. Although many aspects of NAFLD pathogenesis have been understood, there is a paucity of effective treatments to be used as the second line when lifestyle modification is insufficient. Curcumin, a natural polyphenol from turmeric, has been shown to be effective against development of hepatic steatosis and its progression to steatohepatitis, yet these beneficial effects have not been explored in clinical practice. The aim of this study is to investigate the effects of curcumin on hepatic fat content as well as biochemical and anthropometric features of patients with NAFLD. In this randomized double-blind placebo-controlled trial, patients with ultrasonographic evidence of NAFLD were randomly assigned to receive an amorphous dispersion curcumin formulation (500 mg/day equivalent to 70 mg curcumin) or matched placebo for a period of 8 weeks. Liver fat content (assessed through ultrasonography), glycemic and lipid profile, transaminase levels, and anthropometric indices were evaluated at baseline and at the end of follow-up period. The clinical trial protocol was registered under the Iranian Registry of Clinical Trials ID: IRCT2014110511763N18. Compared with placebo, curcumin was associated with a significant reduction in liver fat content (78.9% improvement in the curcumin vs 27.5% improvement in the placebo group). There were also significant reductions in body mass index and serum levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glucose, and glycated hemoglobin compared with the placebo group. Curcumin was safe and well tolerated during the course of trial. Findings of the present proof-of-concept trial suggested improvement of different features of NAFLD after a short-term supplementation with curcumin. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270873 TI - Chemoenzymatic synthesis and utilization of a SAM analog with an isomorphic nucleobase. AB - SalL, an enzyme that catalyzes the synthesis of SAM from l-methionine and 5' chloro-5'-deoxyoadenosine, is shown to accept 5'-chloro-5'-deoxythienoadenosine as a substrate and facilitate the synthesis of a synthetic SAM analog with an unnatural nucleobase. This synthetic cofactor is demonstrated to replace SAM in the DNA methylation reaction with M.TaqI. PMID- 27270874 TI - Cannabis and alcohol use, affect and impulsivity in psychiatric out-patients' daily lives. AB - BACKGROUND AND AIMS: Cannabis and alcohol are the most commonly used (il)licit drugs world-wide. We compared the effects of cannabis and alcohol use on within person changes in impulsivity, hostility and positive affect at the momentary and daily levels, as they occurred in daily life. DESIGN: Observational study involving ecological momentary assessments collected via electronic diaries six random times a day for 28 consecutive days. SETTING: Out-patients' everyday life contexts in Columbia, MO, USA. PARTICIPANTS: Ninety-three adult psychiatric out patients (85% female; mean = 30.9 years old) with borderline personality or depressive disorders, who reported using only cannabis (n = 3), only alcohol (n = 58) or both (n = 32) at least once during the study period. MEASUREMENTS: Real time, standard self-report measures of impulsivity, hostility and positive affect, as impacted by momentary reports of cannabis and alcohol use. FINDINGS: Cannabis use was associated with elevated feelings of impulsivity at the day level [b = 0.83, 95% confidence interval (CI) = 0.17-1.49] and increased hostility at the momentary (b = 0.07, 95% CI = 0.01-0.12) and person (b = 0.81, 95% CI = 0.15-1.47) level. Alcohol use was associated with elevated feelings of impulsivity at the momentary (b = 0.42, 95% CI = 0.13-0.71) and day levels (b = 0.82, 95% CI = 0.22-1.41) and increased positive affect at the momentary (b = 0.12, 95% CI = 0.06-0.18) and day (b = 0.33, 95% CI = 0.16-0.49) levels. CONCLUSIONS: Cannabis and alcohol use are associated with increases in impulsivity (both), hostility (cannabis) and positive affect (alcohol) in daily life, and these effects are part of separate processes that operate on different time-scales (i.e. momentary versus daily). PMID- 27270876 TI - Single-Fiber Recordings of Nociceptive Fibers in Patients With HSAN Type V With Congenital Insensitivity to Pain. AB - OBJECTIVES: Nerve growth factor (NGF) is a protein important for growth and survival, but also for modulation of sensitivity of nociceptors and sympathetic neurons. The purpose of the present study was to investigate the effects of reduced NGF signaling in patients with hereditary sensory and autonomic neuropathies type V, congenital insensitivity to pain, caused by a mutation of the NGFbeta gene, including a characterization of single nociceptive fibers using microneurography (MNG). MATERIALS AND METHODS: One homozygote and 2 heterozygote patients with this mutation were examined with electromyography/neurography, thermal testing, quantitative sudomotor axon reflex test, and electrically induced axon reflex erythema in addition to MNG. RESULTS: Low quantitative sudomotor axon reflex test measurements of 0.02 (left foot) and 0.03 (right foot) MUL/cm and elevated thermal thresholds for warmth and cold detection testing showed clear impairment of small nerve fibers, both sudomotor efferent and somatic afferent fibers, in the patient homozygote for the mutation. MNG from one of the heterozygote patients revealed changes in the small nociceptive fibers in skin, including abnormally low conduction velocity, spontaneous activity in A delta fibers and C-nociceptors and abnormal or lacking response to heat. DISCUSSION: The findings of grossly intact pain thresholds compared with anamnestic insensitivity of pain in deep somatic tissue such as bone suggest a gradient of impairment dependent on different NGF availability in various tissues. Even though these patients in some aspects report insensitivity to pain, they also report chronic spontaneous pain as their main symptom, strikingly highlighting differential mechanisms of insensitivity to evoked pain versus spontaneous pain. PMID- 27270875 TI - Establishment and characterization of a new human myxoid liposarcoma cell line (DL-221) with the FUS-DDIT3 translocation. AB - Myxoid liposarcoma has the pathognomonic fusion oncogene FUS-DDIT3 encoding a chimeric transcription factor. Metastatic risk is higher with an increased round cell component and has been linked to aberrations involving the IGFR/PI3K/AKT pathway. These molecular insights have yet to translate to targeted therapies, and the lack of experimental models is a major hindrance. We describe the initial in-depth characterization of a new cell line (DL-221) and establishment of a mouse xenograft model. The cell line DL-221 was derived from a metastatic pleural lesion showing myxoid and round cell histology. This newly established cell line was characterized for phenotypic properties and molecular cytogenetic profile, using PCR, COBRA-FISH, and western blot. Next-generation whole-exome sequencing was performed to further characterize the cell line and the parent tumor. NOD SCID-IL2R gamma knockout mice were xenograft hosts. DL-221 cells grew an adhering monolayer and COBRA-FISH showed an aneuploid karyotype with t(12;16)(q13;p11) and several other rearrangements; RT-PCR demonstrated a FUS-DDIT3 fusion transcript type 1. Both the cell line and the original tumor harbored a TP53 compound heterozygous mutation in exon 4 and 7, and were wild-type for PIK3CA. Moreover, among the 1254 variants called by whole-exome sequencing, there was 77% concordance between the cell line and parent tumor. The recently described hotspot mutation in the TERT promoter region in myxoid liposarcomas was also found at C228T in DL-221. Xenografts suitable for additional preclinical studies were successfully established in mice after subcutaneous injection. The established DL-221 cell line is the only published available myxoid liposarcoma cell line that underwent spontaneous immortalization, without requiring SV40 transformation. The cell line and its xenograft model are unique and helpful tools to study the biology and novel potential-targeted treatment approaches for myxoid liposarcoma. PMID- 27270877 TI - Hierarchical Manipulation of Block Copolymer Patterns on 3D Topographic Substrates: Beyond Graphoepitaxy. AB - Templates of complex nanopatterns in a form of hierarchically sequenced dots and stripes can be generated in block copolymer films on lithography-free 3D topographic substrates. The approach exploits thickness- and swelling-responsive morphological behavior of block copolymers, and demonstrates novel possibilities of topography-guided registration of nanopatterns due to periodic confinement and spontaneous orthogonal flow-fields. PMID- 27270878 TI - Early prediction of twin-to-twin transfusion syndrome: systematic review and meta analysis. AB - OBJECTIVE: To assess the role of first- and early second-trimester markers in the prediction of twin-to-twin transfusion syndrome (TTTS) in monochorionic twin pregnancies. METHODS: Electronic databases MEDLINE, EMBASE and ClinicalTrials.gov were searched from inception to April 2014, using the MeSH term 'fetofetal transfusion' in combination with phrases 'predictive value', 'sensitivity', 'specificity', 'false positive', 'false negative', 'screening', 'accuracy' and 'ROC'. Study quality was assessed using the PRISMA guidelines and QUADAS-2 tool. A meta-analysis was planned for the following predictive factors: intertwin nuchal translucency (NT) discrepancy; NT > 95th percentile in at least one twin; intertwin crown-rump length (CRL) discrepancy as a percentage of the larger CRL; abnormal ductus venosus (DV) flow in at least one twin. The outcome assessed was TTTS, defined according to the presence of a twin oligohydramnios-polyhydramnios sequence. The diagnostic performance of the predictive factors was evaluated for each included study. RESULTS: The electronic search identified 152 records, of which 23 were assessed in full for eligibility. We identified 13 eligible studies that reported the predictive accuracy of ultrasound parameters, measured before 16 weeks, for the development of TTTS, including a total of 1991 pregnancies, of which 323 developed TTTS. An increased risk of TTTS was associated with: intertwin NT discrepancy (positive likelihood ratio (LR+), 1.92 (95% CI, 1.25 2.96); negative likelihood ratio (LR-), 0.65 (95% CI, 0.50-0.84)); NT > 95th percentile (LR+, 2.63 (95% CI, 1.51-4.58); LR-, 0.85 (95% CI, 0.75-0.96)); CRL discrepancy > 10% (LR+, 1.80 (95% CI, 1.05-3.07); LR-, 0.92 (95% CI, 0.81-1.05)); abnormal DV flow (LR+, 4.77 (95% CI, 1.33-17.04; LR-, 0.49 (95% CI, 0.17-1.41)). The highest sensitivities were observed for intertwin NT discrepancy (52.8% (95% CI, 43.8-61.7%)) and abnormal DV flow (50.0% (95% CI, 33.4-66.6%)). CONCLUSION: Monochorionic twin pregnancies with intertwin NT discrepancy, NT > 95th percentile, intertwin CRL discrepancy > 10% or abnormal DV flow on first trimester ultrasound examination are at significantly increased risk of developing TTTS. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27270879 TI - Subtilisin-like protease-1 secreted through type IV secretion system contributes to high virulence of Streptococcus suis 2. AB - Streptococcus suis serotype 2 is an emerging zoonotic pathogen that triggered two outbreaks of streptococcal toxic shock syndrome (STSS) in China. Our previous research demonstrated that a type IV secretion system (T4SS) harbored in the 89K pathogenicity island contributes to the pathogenicity of S. suis 2. In the present study, a shotgun proteomics approach was employed to identify the effectors secreted by T4SS in S. suis 2, and surface-associated subtilisin-like protease-1 (SspA-1) was identified as a potential virulence effector. Western blot analysis and pull-down assay revealed that SspA-1 secretion depends on T4SS. Knockout mutations affecting sspA-1 attenuated S. suis 2 and impaired the pathogen's ability to trigger inflammatory response in mice. And purified SspA-1 induced the secretion of IL-6, TNF-alpha, and IL-12p70 in THP-1 cells directly. SspA-1 is the first T4SS virulence effector reported in Gram-positive bacteria. Overall, these findings allow us to gain further insights into the pathogenesis of T4SS and STSS. PMID- 27270880 TI - Gating of the two-pore cation channel AtTPC1 in the plant vacuole is based on a single voltage-sensing domain. AB - The two-pore cation channel TPC1 operates as a dimeric channel in animal and plant endomembranes. Each subunit consists of two homologous Shaker-like halves, with 12 transmembrane domains in total (S1-S6, S7-S12). In plants, TPC1 channels reside in the vacuolar membrane, and upon voltage stimulation, give rise to the well-known slow-activating SV currents. Here, we combined bioinformatics, structure modelling, site-directed mutagenesis, and in planta patch clamp studies to elucidate the molecular mechanisms of voltage-dependent channel gating in TPC1 in its native plant background. Structure-function analysis of the Arabidopsis TPC1 channel in planta confirmed that helix S10 operates as the major voltage sensing site, with Glu450 and Glu478 identified as possible ion-pair partners for voltage-sensing Arg537. The contribution of helix S4 to voltage sensing was found to be negligible. Several conserved negative residues on the luminal site contribute to calcium binding, stabilizing the closed channel. During evolution of plant TPC1s from two separate Shaker-like domains, the voltage-sensing function in the N-terminal Shaker-unit (S1-S4) vanished. PMID- 27270881 TI - Antithrombin controls tumor migration, invasion and angiogenesis by inhibition of enteropeptidase. AB - Antithrombin is a key inhibitor of the coagulation cascade, but it may also function as an anti-inflammatory, anti-angiogenic, anti-viral and anti-apoptotic protein. Here, we report a novel function of antithrombin as a modulator of tumor cell migration and invasion. Antithrombin inhibited enteropeptidase on the membrane surface of HT-29, A549 and U-87 MG cells. The inhibitory process required the activation of antithrombin by heparin, and the reactive center loop and the heparin binding domain were essential. Surprisingly, antithrombin non covalently inhibited enteropeptidase, revealing a novel mechanism of inhibition for this serpin. Moreover, as a consequence of this inhibition, antithrombin was cleaved, resulting in a molecule with anti-angiogenic properties that reduced vessel-like formation of endothelial cells. The addition of antithrombin and heparin to U-87 MG and A549 cells reduced motility in wound healing assays, inhibited the invasion in transwell assays and the degradation of a gelatin matrix mediated by invadopodia. These processes were controlled by enteropeptidase, as demonstrated by RNA interference experiments. Carcinoma cell xenografts in nude mice showed in vivo co-localization of enteropeptidase and antithrombin. Finally, treatment with heparin reduced experimental metastasis induced by HT29 cells in vivo. In conclusion, the inhibition of enteropeptidase by antithrombin may have a double anti-tumor effect through inhibiting a protease involved in metastasis and generating an anti-angiogenic molecule. PMID- 27270883 TI - Validation of a prediction model for post-discharge nausea and vomiting after general anaesthesia in a cohort of Swedish ambulatory surgery patients. AB - BACKGROUND: In ambulatory surgery, post-discharge nausea and vomiting (PDNV) has been identified as a significant problem occurring in more than one-third of patients. OBJECTIVE: To validate a simplified PDNV score in a Swedish population. DESIGN: Prospective observational study. SETTING: Two county hospitals in Sweden: Sundsvall from June 2012 to May 2013 and Sunderbyn from January to October 2014. PATIENTS: Adult patients undergoing ambulatory surgery under general anaesthesia. MAIN OUTCOME MEASURES: Postoperative outcomes with a focus on nausea and vomiting were collected at 2, 4, and 6 h after surgery and on the first three postoperative days. The simplified PDNV score, calculated before discharge, included the factors: female sex, age less than 50 years, history of postoperative nausea and vomiting, postoperative nausea and opioids given postoperatively. The prediction performance of the simplified PDNV score was evaluated in terms of discrimination (area under receiver-operating characteristics curve) and calibration plots and was compared with that of the original development study. RESULTS: A total of 559 patients were asked to participate, of which 431 were included in the final study cohort. The overall risk of postoperative nausea and vomiting and PDNV were 18.8 [95% confidence interval (CI), 15.4-22.8]% and 28.1 (95% CI, 24.0-32.5)%, respectively. The discrimination capacity of the simplified PDNV score in our study was similar to that of the original dataset [area under the curve 0.693 (95% CI, 0.638-0.748) vs. 0.706 (0.681-0.731), absolute difference 0.013]. The slope of the calibration curve was 0.893, with a constant of 0.021 (R-square 0.884). CONCLUSION: In a Swedish cohort of patients, the simplified PDNV score performs well in discriminating between patients who will experience post-discharge nausea and/or vomiting after ambulatory surgery. Our results indicate that the simplified PDNV score is as valid in other cohorts as it was in the original development cohort. PMID- 27270884 TI - Transforming the learning outcomes of anaesthesiology training into entrustable professional activities: A Delphi study. AB - BACKGROUND: True competency-based medical education should produce graduates meeting fixed standards of competence. Current postgraduate programmes are usually based on a pre-determined length of time in training making them poorly suited for an individual approach. The concept of entrustable professional activities (EPAs) enables a more flexible, personalised and less time-dependent approach to training programmes. An EPA is a unit of professional practice, to be entrusted to a trainee to execute without supervision once they demonstrate sufficient competence. As EPAs relate competencies to clinical practice, they structure training and assessment more logically according to the way clinicians actually work. A first step in building an EPA-based curriculum is to identify the core EPAs of the profession. OBJECTIVES: The aim of this study was to identify EPAs for postgraduate training in anaesthesiology and to provide an example of how an existing curriculum can be transformed into an EPA-based curriculum. DESIGN: A modified Delphi method was used as a consensus approach applying three Delphi rounds. SETTING: Postgraduate specialty training in anaesthesiology in the Netherlands. PARTICIPANTS: All programme directors in anaesthesiology in the Netherlands except for a single programme director who was involved as a researcher in this study and could not participate. MAIN OUTCOME MEASURES: Agreement among participants on a list of EPAs. Agreement was specified as a consensus rate of more than 80%. RESULTS: In this study, 27 programme directors (69% overall response rate) reached consensus on a set of 45 EPAs that describe a curriculum in anaesthesiology for the Netherlands. CONCLUSION: This study is a first step toward a more contemporary curriculum in competency-based postgraduate anaesthesiology training. PMID- 27270885 TI - Survival after long-term isoflurane sedation in critically ill surgical patients. PMID- 27270887 TI - Worsening Stroke Symptoms in an 80-Year-Old Man. PMID- 27270889 TI - Influence of TMAO and urea on the structure of water studied by inelastic X-ray scattering. AB - We present a study on the influence of the naturally occurring organic osmolytes tri-methylamine N-oxide (TMAO) and urea on the bulk structure of water using X ray Raman scattering spectroscopy. Addition of TMAO is known to stabilize proteins in otherwise destabilizing aqueous urea solutions. The experimental X ray Raman scattering spectra change systematically with increasing solute concentration revealing different effects on the structure of water due to the presence of the two osmolytes. Although these effects are distinct for both molecular species, they have mutually compensating influences on the spectra of the ternary water-TMAO-urea mixtures. This compensation effect seen in the spectra vanishes only at the highest studied ternary concentration of 4 M : 4 M (TMAO : urea). Our experiment shows that the hydrogen-bonding structure of water remains rather intact in the presence of the aforementioned osmolytes if both of them are present. PMID- 27270890 TI - Psychosocial presentation of female bariatric surgery patients after multiple revisional surgeries: A qualitative study. AB - Bariatric surgery is currently the most viable and cost-effective treatment for obesity. This study aimed to understand, from a female patient's perspective, what contributed to not achieving or maintaining excess weight loss from a primary laparoscopic adjustable gastric band surgery, leading to subsequent multiple revisional bariatric surgeries. The purposive sample of participants ( N = 17 females) were over 18 years, had a primary failed laparoscopic adjustable gastric band and had more than three revisional procedures. Participants were individually interviewed and data were analysed from a grounded theory methodology to build a causal model with the core category of unrealistic expectations of bariatric surgery and other important conceptual categories. PMID- 27270888 TI - The ORF3 Protein of Genotype 1 Hepatitis E Virus Suppresses TLR3-induced NF kappaB Signaling via TRADD and RIP1. AB - Hepatitis E virus (HEV) genotype 1 infection is common and can emerge as outbreaks in developing areas, thus posing a threat to public health. However, due to the absence of feasible animal models, the mechanism of HE pathogenesis remains obscure. The HEV pathogenic mechanism has been suggested to be mediated by the immune system and not by direct viral duplication. We firstly discovered that the open reading frame 3 (ORF3) protein of genotype 1 HEV downregulates TLR3 mediated NF-kappaB signaling in Human A549 Lung Epithelial Cells (A549 cells) which were exposed to different TLR agonists associated with viral nucleic acids. Additionally, we identified the P2 domain of ORF3 as being responsible for this inhibition. Intriguingly, tumor necrosis factor receptor 1-associated death domain protein (TRADD) expression and receptor-interacting protein kinase 1 (RIP1) K63-ubiquitination were reduced in the presence of both ORF3 and Poly(I:C). Furthermore, we found that Lys377 of RIP1 acts as the functional ubiquitination site for ORF3-associated inhibition. Overall, we found that ORF3 protein downregulates TLR3-mediated NF-kappaB signaling via TRADD and RIP1. Our findings provide a new perspective on the cellular response in HEV infection and expand our understanding of the molecular mechanisms of HEV pathogenesis in innate immunity. PMID- 27270891 TI - Erratum: Correspondence: Reply to 'Enhancing a phase measurement by sequentially probing a solid-state system'. PMID- 27270893 TI - Anti-TNF drives regulatory T cell expansion by paradoxically promoting membrane TNF-TNF-RII binding in rheumatoid arthritis. AB - The interplay between inflammatory and regulatory pathways orchestrates an effective immune response that provides protection from pathogens while limiting injury to host tissue. Tumor necrosis factor (TNF) is a pivotal inflammatory cytokine, but there is conflicting evidence as to whether it boosts or inhibits regulatory T cells (T reg cells). In this study, we show that the therapeutic anti-TNF antibody adalimumab, but not the soluble TNF receptor etanercept, paradoxically promoted the interaction between monocytes and T reg cells isolated from patients with rheumatoid arthritis (RA). Adalimumab bound to monocyte membrane TNF from RA patients and unexpectedly enhanced its expression and its binding to TNF-RII expressed on T reg cells. As a consequence, adalimumab expanded functional Foxp3(+) T reg cells equipped to suppress Th17 cells through an IL-2/STAT5-dependent mechanism. Our data not only highlight the beneficial effect of membrane TNF on T reg cell numbers during chronic inflammation, but in addition reveal how a therapeutic antibody that is thought to act by simply blocking its target can enhance the regulatory properties of this proinflammatory cytokine. PMID- 27270892 TI - Live cell imaging to understand monocyte, macrophage, and dendritic cell function in atherosclerosis. AB - Intravital imaging is an invaluable tool for understanding the function of cells in healthy and diseased tissues. It provides a window into dynamic processes that cannot be studied by other techniques. This review will cover the benefits and limitations of various techniques for labeling and imaging myeloid cells, with a special focus on imaging cells in atherosclerotic arteries. Although intravital imaging is a powerful tool for understanding cell function, it alone does not provide a complete picture of the cell. Other techniques, such as flow cytometry and transcriptomics, must be combined with intravital imaging to fully understand a cell's phenotype, lineage, and function. PMID- 27270895 TI - Impedimetric detection and lumped element modelling of a hemagglutination assay in microdroplets. AB - Droplet-based microfluidic systems offer tremendous benefits for high throughput biochemical assays. Despite the wide use of electrical detection for microfluidic systems, application of impedimetric sensing for droplet systems is very limited. This is mainly due to the insulating oil-based continuous phase used for most aqueous samples of interest. We present modelling and experimental verification of impedimetric detection of hemagglutination in microdroplets. We have detected agglutinated red blood cells in microdroplets and screened whole blood samples for multiple antibody sera using conventional microelectrodes. We were able to form antibody and whole blood microdroplets in PDMS microchannels without any tedious chemical surface treatment. Following the injection of a blood sample into antibody droplets, we have detected the agglutination-positive and negative droplets in an automated manner. In order to understand the characteristics of impedimetric detection inside microdroplets, we have developed the lumped electrical circuit equivalent of an impedimetric droplet content detection system. The empirical lumped element values are in accordance with similar models developed for single phase electrical impedance spectroscopy systems. The presented approach is of interest for label-free, quantitative analysis of droplets. In addition, the standard electronic equipment used for detection allows miniaturized detection circuitries that can be integrated with a fluidic system for a quantitative microdroplet-based hemagglutination assay that is conventionally performed in well plates. PMID- 27270896 TI - pH-Dependent membrane lysis by using melittin-inspired designed peptides. AB - We developed a membrane-lytic peptide (LP) having 26 amino acid residues composed of a helix-promoting hydrophobic segment (Leu-Ala repetitive sequence) and a cationic segment from melittin. In the presence of liposomes, LP interacts with liposomal surfaces to form a hydrophobic helix in the lipid bilayer in a wide pH range. In order to provide LP with a weakly acidic (endosomal) pH-controlled membrane-lytic activity, we have designed an LPE peptide series (a typical peptide, LPE3-1) with a hydrophobic segment in which Leu (L) residues are replaced by acidic Glu (E) residues. To analyze the pH-selective membrane-lytic activity of the designed peptides, both calcein leakage and membrane accessibility assays were performed. In the case of membrane disruption induced by the active pore formation, the incorporated calcein would leak from the liposomes and simultaneously the aqueous solution in the membrane surrounding would be accessible to the liposome interior at pH 5.0. The assays in the presence of LPE3-1 indicated no significant leakage or accessibility at pH 7.4, but a typical leakage and some accessibility to liposomes were positively observed at pH 5.0. In order to estimate whether the weakly acidic pH-controlled lytic activity is due to a secondary structural change of the hydrophobic segment of LPE3-1 in the liposome membrane, we have measured circular dichroism spectra. In the presence of liposomes, the minimum showing the characteristic helical structure was observed at 222 nm only under weakly acidic conditions. This pH dependence is in good agreement with the results from the leakage and accessibility assays. The pH-dependent membrane disruption properties of LPE3-1 may open a new avenue to gain insight into the interaction between peptides and lipids for the development of efficient drug/gene delivery systems. PMID- 27270894 TI - Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone. AB - Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ 334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis. PMID- 27270897 TI - Nerve abscess in Hansen's disease as part of immune reconstitution inflammatory syndrome: a case report. AB - Immune reconstitution inflammatory syndrome is an inflammatory reaction in HIV infected patients after initiation of antiretroviral therapy resulting from restored immunity to specific infectious or non-infectious antigens. A 36-year old male patient on highly active antiretroviral therapy of six months duration, presented with reddish, tender lesions over medial aspect of arm and a single, anaesthetic patch. Tender fluctuant swellings were seen on the medial aspect of left forearm. A few of them had ruptured spontaneously discharging pus. A skin biopsy from the anaesthetic patch showed caseating epitheloid granulomas. A diagnosis of Hansen's disease borderline tuberculoid in type 1 reversal reaction, with formation of nerve abscess due to Immune Reconstitution Inflammatory Syndrome was made. The patient was started on multibacillary multidrug therapy as per WHO guidelines and highly active antiretroviral therapy was continued. PMID- 27270898 TI - Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia. AB - This study aimed to investigate whether nitric oxide participates in the cardiovascular function and haemodynamic adaptation to acute haemorrhage in animals with thyroid disorders. Sprague-Dawley rats aged 2months old treated with T3 (hyper, 20MUg/100g body weight) or 0.02% methimazole (hypo, w/v) during 28days were pre-treated with N(G) nitro-l-arginine methyl ester (L-NAME) and submitted to 20% blood loss. Heart function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase activity and protein levels were performed. We found that hypo decreased fractional shortening and ejection fraction and increased left ventricle internal diameter. Hyper decreased ventricle diameter and no changes in cardiac contractility. Haemorrhage elicited a hypotension of similar magnitude within 10min. Then, this parameter was stabilized at about 30-40min and maintained until finalized, 120min. L-NAME rats showed that the immediate hypotension would be independent of nitric oxide. Nitric oxide synthase inhibition blunted the changes of heart rate induced by blood loss. Hyper and hypo had lower atrial enzyme activity associated with a decreased enzyme isoform in hypo. In ventricle, hyper and hypo had a higher enzyme activity, which was not correlated with changes in protein levels. Haemorrhage induced an increased heart nitric oxide production. We concluded that thyroid disorders were associated with hypertrophic remodelling which impacted differently on cardiac function and its adaptation to a hypovolemia. Hypovolemia triggered a nitric oxide synthase activation modulating the heart function to maintain haemodynamic homeostasis. This involvement depends on a specific enzyme isoform, cardiac chamber and thyroid state. PMID- 27270899 TI - Naringin protects cardiomyocytes against hyperglycemia-induced injuries in vitro and in vivo. AB - We previously reported that naringin (NRG) protects cardiomyocytes against high glucose (HG)-induced injuries by inhibiting the MAPK pathway. The aim of this study was to test the hypothesis that NRG prevents cardiomyocytes from hyperglycemia-induced insult through the inhibition of the nuclear factor kappa B (NF-kappaB) pathway and the upregulation of ATP-sensitive K(+) (KATP) channels. Our results showed that exposure of cardiomyocytes to HG for 24h markedly induced injuries, as evidenced by a decrease in cell viability and oxidative stress, and increases in apoptotic cells as well as the dissipation of mitochondrial membrane potential (MMP). These injuries were markedly attenuated by the pretreatment of cells with either NRG or pyrrolidine dithiocarbamate (PDTC) before exposure to HG. Furthermore, in streptozotocin (STZ)-induced diabetic rats and in HG-induced cardiomyocytes, the expression levels of caspase-3, bax and phosphorylated (p)-NF kappaB p65 were increased. The increased protein levels were ameliorated by pretreatment with both NRG and PDTC. However, the expression levels of bcl-2 and KATP and superoxide dismutase (SOD) activity were decreased by hyperglycemia; the expression level of Nox4 and the ADP/ATP ratio were increased by hyperglycemia. These hyperglycemia-induced indexes were inhibited by the pretreatment of cardiomyocytes with NRG or PDTC. In addition, in STZ-induced diabetic rats, we also observed that NRG or PDTC contributed to protecting mitochondrial injury and myocardium damage. This study demonstrated that NRG protects cardiomyocytes against hyperglycemia-induced injury by upregulating KATP channels in vitro and inhibiting the NF-kappaB pathway in vivo and in vitro. PMID- 27270900 TI - Acute muscle and joint mechanical responses following a high-intensity stretching protocol. AB - PURPOSE: A previous study observed a joint passive torque increase above baseline ~30 min after a high-intensity stretching. This study examined the effect of a high-intensity stretching on ankle dorsiflexion passive torque, medial gastrocnemius (MG) shear modulus, and plantar flexors maximal voluntary isometric force (MVIC). METHOD: Participants (n = 11, age 27.2 +/- 6.5 years, height 172.0 +/- 10.0 cm, weight 69.5 +/- 10.4 kg) underwent two stretching sessions with plantar flexors isometric contractions performed: (1) 5 min before, 1 min after, and every 10 min after stretching (MVC session); (2) 5 min before, and 60 min after the stretching (no-MVC session). RESULTS: In both sessions, no changes were observed for MG shear modulus (p > 0.109). In the no-MVC session, passive torque decreased 1 min after stretching (-7.5 +/- 8.4 %, p = 0.015), but increased above baseline 30 min after stretching (+6.3 +/- 9.3 %, p = 0.049). In the MVC session, passive torque decreased at 1 min (-10.1 +/- 6.3 %, p < 0.001), 10 min (-6.3 +/- 8.2 %, p = 0.03), 20 min (-8.0 +/- 9.2 %, p = 0.017), and 60 min (-9.2 +/- 12.4 %, p = 0.034) after the stretching, whereas the MVIC decreased at 1 min (-5.0 +/- 9.3 %, p = 0.04) and 10 min (-6.7 +/- 8.7 %, p = 0.02) after stretching. CONCLUSION: The ankle passive torque increase 30 min following the stretch was not due to the MG shear modulus response; consequently, response may be due to changes in surrounding connective tissue mechanical properties. PMID- 27270901 TI - Comparison of KRAS mutation status between primary tumor and metastasis in Chinese colorectal cancer patients. AB - Detection of KRAS mutation status is a routine clinical procedure for predicting response to anti-EGFR therapy in colorectal cancer (CRC) patients. Previous studies showed high concordance of KRAS mutation status in primary lesion and corresponding metastatic sites in CRC. However, the data were mostly from Caucasians. The aim of this study is to compare KRAS mutation and other molecules mutation status between primary tumor and corresponding metastatic lesion in Chinese patients with CRC. In this retrospective study, Chinese CRC patients with paired samples of primary tumor and metastatic site were detected for KRAS codon 12 and 13 with quantitative real-time PCR, or detected for OncoCartaTM panel of 19 genes with MassARRAY((r)) technique, including KRAS, BRAF, NRAS and PIK3CA et al. Forty-eight paired CRC samples were analyzed for KRAS codon 12 and 13 using quantitative real-time PCR. Ten paired samples were analyzed by 19 genes OncoCartaTM Panel with MassARRAY((r)) technique. KRAS mutation was found in 15 (25.9 %) primary tumors and 18 (31.0 %) metastases. The discordance of KRAS was observed in 11 (19.0 %) patients. Alteration of mutation points in primary site with mutant KRAS was not observed. In the 10 patients with multiple gene detection, PIK3CA mutation showed concordant mutation status in primary tumor and metastatic site, whereas discordance in BRAF, NRAS and AKT1 was detected. A concordance rate of 81.0 % was detected in KRAS mutation between primary tumor and metastatic lesion in Chinese patients with CRC. Discordance of BRAF, NRAS and AKT1 mutation status in primary tumor and metastases was observed. PMID- 27270902 TI - Microbial complexes levels in conventional and self-ligating brackets. AB - OBJECTIVES: The aims were to evaluate the levels of bacterial species in saliva and in situ and to assess whether the design of brackets influences the risk of developing periodontal disease. MATERIALS AND METHODS: Twenty patients (13.3 mean age) were bonded with self-ligating brackets and a conventional bracket. Saliva was collected before bonding and 30 and 60 days after bonding. One sample of each bracket was removed 30 and 60 days after bonding. The analysis was determined by checkerboard DNA-DNA hybridization. The data was evaluated by the non-parametric test. RESULTS: A significant increase in the levels of bacterial species in the saliva occurred in 15 of the 22 analyzed species. The self-ligating brackets presented the highest incidence percentages for the orange and red complexes 60 days after bonding. In situ analyses showed different patterns according to the bracket design. The levels of Campylobacter rectus showed significant differences (p = 0.011) 60 days after bonding among the three brackets; the highest values were observed in the In-Ovation(r)R bracket. CONCLUSIONS: The bracket design seems to influence the levels of bacterial species involved in periodontal disease. Considering the wide variety of bacterial species, additional studies are needed to aid in the establishment of effective protocols to prevent the development of periodontal disease during orthodontic treatment. CLINICAL RELEVANCE: A dynamic alteration in the oral microbiota may lead to inflammatory reactions in the supporting soft and hard tissues. The different types of brackets interfere with bacterial adherence. Bracket design should be considered in orthodontic treatment. PMID- 27270903 TI - Comparison of periodontal ligament and gingiva-derived mesenchymal stem cells for regenerative therapies. AB - OBJECTIVES: Tissue-engineering therapies using undifferentiated mesenchymal cells (MSCs) from intra-oral origin have been tested in experimental animals. This experimental study compared the characteristics of undifferentiated mesenchymal stem cells from either periodontal ligament or gingival origin, aiming to establish the basis for the future use of these cells on regenerative therapies. MATERIALS AND METHODS: Gingiva-derived mesenchymal stem cells (GMSCs) were obtained from de-epithelialized gingival biopsies, enzymatically digested and expanded in conditions of exponential growth. Their growth characteristics, phenotype, and differentiation ability were compared with those of periodontal ligament-derived mesenchymal stem cells (PDLMSCs). RESULTS: Both periodontal ligament- and gingiva-derived cells displayed a MSC-like phenotype and were able to differentiate into osteoblasts, chondroblasts, and adipocytes. These cells were genetically stable following in vitro expansion and did not generate tumors when implanted in immunocompromised mice. Furthermore, under suboptimal growth conditions, GMSCs proliferated with higher rates than PDLMSCs. CONCLUSIONS: Stem cells derived from gingival biopsies represent bona fide MSCs and have demonstrated genetic stability and lack of tumorigenicity. CLINICAL RELEVANCE: Gingiva-derived MSCs may represent an accessible source of messenchymal stem cells to be used in future periodontal regenerative therapies. PMID- 27270904 TI - Gustatory function and taste perception in patients with oral lichen planus and tongue involvement. AB - OBJECTIVES: The aim of the study was to evaluate if patients with oral lichen planus (OLP) and tongue involvement have impaired taste function and if there is an association to the perception of pain. MATERIAL AND METHODS: The test group included patients with OLP and involvement of the tongue without treatment (n = 20). Control subjects had no mucosal or systemic disease affecting taste function and were matched for age and gender (n = 20). Patients' intraoral pain and subjective perception of taste were recorded on a visual analog scale. Taste function was assessed by means of the "taste strips." RESULTS: Measured taste function was slightly but significantly decreased in OLP patients compared to control subjects (p = 0.01). Self-rated taste perception did not differ in both groups (p = 0.8). Post hoc analysis showed that particularly the taste quality "sour" was most affected by the OLP status (p = 0.01). There were no correlations between pain and subjective/objective taste perception. CONCLUSION: Untreated OLP subjects have lower gustatory function, which they are not aware of. CLINICAL RELEVANCE: Impaired gustatory function in patients with OLP may affect patient's quality of life. Further studies on larger samples sizes are requested. PMID- 27270905 TI - Paediatric Drug Development and Formulation Design-a European Perspective. AB - The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize "better" medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the "Guideline on the Pharmaceutical Development of Medicines for Paediatric Use." Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions. PMID- 27270906 TI - Routine radiographs at time of pin removal after closed reduction and percutaneous pinning for type 2 supracondylar humerus fractures do not change management: a retrospective cohort study. AB - PURPOSE: Radiographs are usually taken on day of pin removal for children treated with closed reduction and percutaneous pinning (CRPP) of type 2 supracondylar humerus fractures. The purpose of this study was to determine whether radiographs taken at time of pin removal for patients recovering uneventfully alter management. METHODS: After IRB approval, billing records identified 1213 patients aged 1-10 years who underwent elbow surgery between 2007 and 2013 at our institution for a supracondylar humerus fracture. Of these patients, 389 met inclusion criteria. Clinical charts were reviewed for demographics, operative details, and clinical follow-up, focusing on clinical symptoms present at pin removal. Radiographs taken at time of pin removal and subsequent visits were assessed for healing and fracture alignment. RESULTS: In no case was pin removal delayed based on radiographs. One hundred and nineteen (31 %) patients had radiographs taken following pin removal; in no case was loss of reduction found among these patients. No cases of neurologic or vascular injury, re-fracture, or loss of reduction occurred. Infection occurred in 12 patients (3 %). Pins were kept in place for 23.8 +/- 4.4 days. Eighty-six patients (22 %) had additional intervention after pin removal (cast application in all cases). Of 389 patients, 75 (19 %) had no documented reason for extended casting, four (1 %) were extended based on physician evaluation of radiographs, and seven (2 %) were extended for other reasons. CONCLUSIONS: Elimination of radiographs at time of pin removal should be considered. If continuing to obtain radiographs at pin removal, we recommend removing pins before taking radiographs to reduce patient fear and anxiety from visualizing percutaneous pins. PMID- 27270907 TI - [Bone metastases : New aspects of pathogenesis and systemic therapy]. AB - The occurrence of bone metastases, in particular secondary to breast and prostate cancer, represents a complex medical condition that is debilitating for affected patients. In order to provide an efficient and personalized therapy, an interdisciplinary treatment approach is mandatory; therefore, systemic pharmacological therapy represents a core element of the overall treatment concept. In terms of pathophysiology, the cancer cells cause a massive disturbance of the local bone microenvironment, which as a rule leads to activation of bone resorbing osteoclasts. In addition to bisphosphonates, which can be considered classical antiresorptive agents, the monoclonal receptor activator of nuclear factor-kappa B ligand (RANKL) antibody denosumab has been in use in clinical practice since 2011. The alpha-emitting radioisotope Alpharadin was also recently approved for the treatment of metastatic prostate cancer. This article provides a summary of the most recent knowledge on the pathogenesis of how cancer cells alter the bone microenvironment as well as a review of established and future systemic treatment options. PMID- 27270908 TI - Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma. AB - IDH1 mutated glioblastoma (GB) has a better prognosis than IDH1 wildtype GB. However, it remains unknown whether patients (pts) with IDH1 mutated GB have a higher 6-month progression free survival (PFS6) or radiographic response (RR) rate on clinical trials for recurrence. Retrospective review of GB pts at MDACC between 2006 and 2012 identified 330 patients in recurrent GB trials. 93 patients (28 %) had either PFS6 or a complete/partial RR per RANO criteria. 49/93 (53 %) patients with PFS6 or a complete/partial RR had tumor tissue for IDH1 testing. A matched cohort of 49 patients on recurrent GB clinical trials that failed to achieve PFS6 or RR (also with tissue for IDH1 testing) was identified for comparison. IDH1 status was obtained in 92/98 (94 %) patients of which 17 (18 %) had an IDH1 mutation. PFS6 was seen in 26/49 (53 %) patients. IDH status was unknown in two of these patients. 5/24 (21 %) were IDH1 mutated compared to 5/24 (21 %) of their matched cohort without PFS6. RR was found in 47/49 (94 %) patients. IDH status was unknown in four of these patients. IDH1 mutation was present in 7/43 (16 %) patients with RR compared to 10/43 (23 %) in the matched cohort without RR (p = 0.48). Median OS for trials at first recurrence was 9.8 months for IDH1 wildtype GB vs. 19.32 months for IDH1 mutated GB (p = 0.14). IDH1 mutation status was not predictive of PFS6 or RR in recurrent GB trials for this data set. However, further examination in larger randomized prospective studies is needed. PMID- 27270909 TI - Kidney transplantation from deceased donors with elevated serum creatinine. AB - BACKGROUND: Elevated donor serum creatinine has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of elevated donor serum creatinine on short and long-term outcomes and to determine possible ways to optimize the use of these organs. METHODS: All kidney transplants from 01-2000 to 12-2012 with donor creatinine >= 2 mg/dl were considered. Risk factors for delayed graft function (DGF) were explored with uni- and multivariate regression analyses. Donor and recipient data were analyzed with uni- and multivariate cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. RESULTS: Seventy-eight patients were considered. Median recipient age and waiting time on dialysis were 53 years and 5.1 years, respectively. After a median follow-up of 6.2 years, 63 patients are alive. 1, 3, and 5-year graft and patient survival rates were 92, 89, and 89 % and 96, 93, and 89 %, respectively. Serum creatinine level at procurement and recipient's dialysis time prior to KT were predictors of DGF in multivariate analysis (p = 0.0164 and p = 0.0101, respectively). Charlson comorbidity score retained statistical significance by multivariate regression analysis for graft survival (p = 0.0321). Recipient age (p = 0.0035) was predictive of patient survival by multivariate analysis. CONCLUSIONS: Satisfactory long-term kidney transplant outcomes in the setting of elevated donor serum creatinine >=2 mg/dl can be achieved when donor creatinine is <3.5 mg/dl, and the recipient has low comorbidities, is under 56 years of age, and remains in dialysis prior to KT for <6.8 years. PMID- 27270910 TI - A rare cause of pyrexia in a transplant patient: Questions. PMID- 27270911 TI - A rare cause of pyrexia in a transplant patient: Answers. PMID- 27270912 TI - Impacting Health Disparities in Urban Communities: Preparing Future Healthcare Providers for "Neighborhood-Engaged Care" Through a Community Engagement Course Intervention. AB - It is well known that health disparities exist and that a significant majority of patients who suffer disproportionately from them are lower income, non-white residents of dense, and diverse urban neighborhoods. It is our belief that factors hindering the reduction of health disparities in these neighborhoods are a lack of a framework and preparation needed to engage these communities in identifying specific health care needs. This paper describes one curricular intervention, a graduate level community engagement course, developed within an academic medical center located in an urban setting, that demonstrates promise in effecting change in the extent to which clinicians are able to engage communities and practice "neighborhood-engaged care" with the central goal of mitigating disparities. PMID- 27270913 TI - Use of self-monitoring tools in a clinic sample of adults with type 2 diabetes. AB - Self-monitoring is an effective strategy for chronic disease management; many readily available mobile applications allow tracking of diabetes-related health behaviors but their use has not yet been integrated into routine clinical care. How patients engage with these applications in the real world is not well understood. The specific aim of this study is to survey adults with type 2 diabetes (T2D) regarding self-monitoring behaviors, including mobile application use. In 2015, we surveyed an adult diabetes clinic population (n = 96) regarding self-monitoring behaviors: diet, physical activity, weight, and blood glucose. Self-monitoring with any method ranged from 20-90 %. About half of the participants owned smartphones; few had mobile applications. The most common app tracked behavior was physical activity, then weight and diet. Despite numerous available mobile health-tracking applications, few T2D adults from our sample used them, though many reported self-monitoring with other methods. PMID- 27270914 TI - Correction: Which New Health Technologies Do We Need to Achieve an End to HIV/AIDS? AB - [This corrects the article DOI: 10.1371/journal.pbio.1002372.]. PMID- 27270915 TI - Perceptions of a Specific Family Communication Application among Grandparents and Grandchildren: An Extension of the Technology Acceptance Model. AB - Many studies have noted that the use of social networks sites (SNSs) can enhance social interaction among the elderly and that the motivation for the elderly to use SNSs is to keep in contact with remote friends and family or the younger generation. Memotree is designed to promote intergenerational family communication. The system incorporates the Family Tree design concept and provides family communication mechanisms based on the Family Communication Scale. In addition, the system optimizes hardware and interface use to conform to the specific needs of older and substantially younger individuals. Regarding the impact of variables on SNS with respect to the interaction of usability variables in the construction of a cross-generational communication platform, we adopted the TAM model and Chung et al.'s suggestions to promote user acceptance of the proposed Memotree system. A total of 39 grandchildren and 39 grandparents met the criteria and were included in the study. The elderly and young respondents revealed substantial willingness to use and/or satisfaction with using the Memotree system. Empirical results indicate that technology affordances and perceived ease of use have a positive impact on perceived usefulness, while perceived ease of use is affected by technology affordances. Internet self efficacy and perceived usefulness have a positive impact on the user's behavioral intention toward the system. In addition, this study investigated age as a moderating variable in the model. The results indicate that grandchildren have a larger significant effect on the path between perceived usefulness and behavioral intention than grandparents. This study proposes a more complete framework for investigating the user's behavioral intention and provides a more appropriate explanation of related services for cross-generational interaction with SNS services. PMID- 27270916 TI - Cav1.4 L-Type Calcium Channels Contribute to Calpain Activation in Degenerating Photoreceptors of rd1 Mice. AB - Retinitis pigmentosa is an inherited blinding disorder characterized by progressive degeneration and loss of photoreceptors. The exact mechanism of degeneration and cell death of photoreceptors is not known, but is thought to involve disturbed Ca2+-signaling. Ca2+ can enter the photoreceptor cell via outer segment cyclic nucleotide-gated (CNG) channels or synaptic Cav1.4 L-type voltage gated calcium channels (VGCC). Previously, we have shown that genetic ablation of the Cngb1 gene encoding the B subunit of the rod CNG channel delays the fast progressing degeneration in the rd1 mutant mouse model of retinitis pigmentosa. In this study, we crossbred rd1 mice with the Cacna1f-deficient mouse lacking the Cav1.4 alpha1 subunit of the L-type VGCC. Longitudinal in vivo examinations of photoreceptor layer thickness by optical coherence tomography revealed a significant, but not sustained delay of retinal degeneration in Cacna1f x rd1 double mutant mice compared to rd1 mice. This was accompanied by a reduction of TUNEL positive cells in the early phase of rod degeneration. Remarkably, Cacna1f x rd1 double mutant mice displayed a strong decrease in the activation of the Ca2+-dependent protease calpain during photoreceptor loss. Our results show that genetic deletion of the synaptic Cav1.4 L-type VGCCs impairs calpain activation and leads to a short-term preservation of photoreceptors in the rd1 mouse. PMID- 27270918 TI - OFFl Models: Novel Schema for Dynamical Modeling of Biological Systems. AB - Flow diagrams are a common tool used to help build and interpret models of dynamical systems, often in biological contexts such as consumer-resource models and similar compartmental models. Typically, their usage is intuitive and informal. Here, we present a formalized version of flow diagrams as a kind of weighted directed graph which follow a strict grammar, which translate into a system of ordinary differential equations (ODEs) by a single unambiguous rule, and which have an equivalent representation as a relational database. (We abbreviate this schema of "ODEs and formalized flow diagrams" as OFFL.) Drawing a diagram within this strict grammar encourages a mental discipline on the part of the modeler in which all dynamical processes of a system are thought of as interactions between dynamical species that draw parcels from one or more source species and deposit them into target species according to a set of transformation rules. From these rules, the net rate of change for each species can be derived. The modeling schema can therefore be understood as both an epistemic and practical heuristic for modeling, serving both as an organizational framework for the model building process and as a mechanism for deriving ODEs. All steps of the schema beyond the initial scientific (intuitive, creative) abstraction of natural observations into model variables are algorithmic and easily carried out by a computer, thus enabling the future development of a dedicated software implementation. Such tools would empower the modeler to consider significantly more complex models than practical limitations might have otherwise proscribed, since the modeling framework itself manages that complexity on the modeler's behalf. In this report, we describe the chief motivations for OFFL, carefully outline its implementation, and utilize a range of classic examples from ecology and epidemiology to showcase its features. PMID- 27270917 TI - Directed Evolution of FLS2 towards Novel Flagellin Peptide Recognition. AB - Microbe-associated molecular patterns (MAMPs) are molecules, or domains within molecules, that are conserved across microbial taxa and can be recognized by a plant or animal immune system. Although MAMP receptors have evolved to recognize conserved epitopes, the MAMPs in some microbial species or strains have diverged sufficiently to render them unrecognizable by some host immune systems. In this study, we carried out in vitro evolution of the Arabidopsis thaliana flagellin receptor FLAGELLIN-SENSING 2 (FLS2) to isolate derivatives that recognize one or more flagellin peptides from bacteria for which the wild-type Arabidopsis FLS2 confers little or no response. A targeted approach generated amino acid variation at FLS2 residues in a region previously implicated in flagellin recognition. The primary screen tested for elevated response to the canonical flagellin peptide from Pseudomonas aeruginosa, flg22. From this pool, we then identified five alleles of FLS2 that confer modest (quantitatively partial) recognition of an Erwinia amylovora flagellin peptide. Use of this Erwinia-based flagellin peptide to stimulate Arabidopsis plants expressing the resulting FLS2 alleles did not lead to a detectable reduction of virulent P. syringae pv. tomato growth. However, combination of two identified mutations into a single allele further increased FLS2-mediated responses to the E. amylovora flagellin peptide. These studies demonstrate the potential to raise the sensitivity of MAMP receptors toward particular targets. PMID- 27270919 TI - In-Office Hyaluronate Injection Laryngoplasty as Palliative Treatment for Unilateral Vocal Fold Paralysis. AB - BACKGROUND: Voice and swallowing impairments can impact on both quality of life and survival. Unilateral vocal fold paralysis (UVFP) as a result of distant metastasis can cause breathy voice and aspiration. The purpose of this study is to develop and evaluate a less invasive and effective alternative therapy for UVFP. METHODS: This was a retrospective review of prospectively enrolled patients at a tertiary referral center in Taiwan. Among a cohort of 177 patients who received intracordal hyaluronate injections, 2 had UVFP from distant metastasis and met the inclusion criteria. Vocal cord motion was recorded by videostroboscopy, and the normalized glottal gap area was measured. Voice quality, defined by speech language pathologists, and swallowing status were compared, and immediate complications after the injection were investigated. RESULTS: Two patients with UVFP with M1 lesions (both lung) accepted the procedure. The glottal gap area was significantly improved 1 month after in office hyaluronate injection. Voice quality and aspiration were also improved. No immediate complications were noted in either patient. CONCLUSIONS: In-office intracordal hyaluronate injection is a safe and effective treatment for UVFP, providing a palliative method to help maintain the patient's voice and quality of life. PMID- 27270920 TI - Performance of clear vacuum-formed thermoplastic retainers depending on retention protocol: a systematic review. AB - We aimed at comparing the performance of vacuum-formed thermoplastic retainers (VFR) worn either full-time or part-time, in maintaining orthodontic treatment results in terms of tooth alignment, arch form and occlusion. We reviewed randomized and prospective controlled clinical trials comparing VFR wearing protocols and searched databases, without restrictions, for published and unpublished literature. The risk of bias was assessed using the Cochrane Risk of Bias tool and the overall level of certainty in the evidence following ADA methodology. 184 studies were initially identified and reduced to the 3 randomized controlled trials included in the systematic review by means of specific criteria. One study followed patients 1 year into retention, and the other two for 6 months. Little's Irregularity Index, intermolar and intercanine width, arch length, overjet and PAR score did not differ significantly between the patients wearing their retainers part time or full time. We observed a slight increase in the overbite in the part-time group in only one trial. With a moderate level of certainty, we found that during the observation period, full time VFR wear is not superior to part-time, bearing in mind the potential implications for health burden, retainer longevity and cost-effectiveness, as well as patient satisfaction and compliance. PMID- 27270921 TI - Parturition pit: the bony imprint of vaginal birth. AB - PURPOSE: To retrospectively evaluate for pits along the dorsum of the pubic body in females and compare the presence/absence of these pits to vaginal birth data. MATERIALS AND METHODS: We retrospectively reviewed females with vaginal birth data who underwent pelvic CT. The presence of pits along the dorsum of the pubic body, pit grade (0 = not present; 1 = faintly imperceptible; 2 = present; 3 = prominent), and the presence of osteitis condensans ilii, preauricular sulcus, and sacroiliac joint vacuum phenomenon were assessed on imaging. Musculoskeletal radiologists who were blinded to the birth data evaluated the CTs. 48 males were also evaluated for the presence of pits. RESULTS: 482 female patients underwent CT pelvis and 171 were excluded due to lack of vaginal birth data. Of the 311 study patients, 262 had prior vaginal birth(s) and 194 had pits on CT. Only 7 of the 49 patients without prior vaginal birth had pits. There was a statistically significant association between vaginal birth and presence of pits (p < 0.0001). Patients with more prominent pits (grades 2/3) had a greater number of vaginal births. As vaginal deliveries increased, the odds of having parturition pits greatly increased, adjusting for age and race at CT (p < 0.0001). No males had pits. CONCLUSION: Our study indicates that parturition pits are associated with prior vaginal birth and should be considered a characteristic of the female pelvis. The lytic appearance of prominent pits on imaging can simulate disease and create a diagnostic dilemma for interpreting radiologists. PMID- 27270922 TI - Acute vertebral fracture after spinal fusion: a case report illustrating the added value of single-source dual-energy computed tomography to magnetic resonance imaging in a patient with spinal Instrumentation. AB - Magnetic resonance imaging (MRI) is degraded by metal-implant-induced artifacts when used for the diagnostic assessment of vertebral compression fractures in patients with instrumented spinal fusion. Dual-energy computed tomography (DECT) offers a promising supplementary imaging tool in these patients. This case report describes an 85-year-old woman who presented with a suspected acute vertebral fracture after long posterior lumbar interbody fusion. This is the first report of a vertebral fracture that showed bone marrow edema on DECT; however, edema was missed by an MRI STIR sequence owing to metal artifacts. Bone marrow assessment using DECT is less susceptible to metal artifacts than MRI, resulting in improved visualization of vertebral edema in the vicinity of fused vertebral bodies. PMID- 27270923 TI - Unskilled and unaware in the classroom: College students' desired grades predict their biased grade predictions. AB - People tend to be overconfident when predicting their performance on a variety of physical and mental tasks (i.e., they predict they will perform better than they actually do). Such a pattern is commonly found in educational settings, in which many students greatly overestimate how well they will perform on exams. In particular, the lowest-performing students tend to show the greatest overconfidence (i.e., the "unskilled-and-unaware" effect). Such overconfidence can have deleterious effects on the efficacy of students' short-term study behaviors (i.e., underpreparing for exams) and long-term academic decisions (i.e., changing one's academic major to an "easier" topic or dropping out of school completely). To help understand why students' grade predictions are often overconfident, we examined the hypothesis that students' grade predictions are biased by their desired levels of performance, which are often much higher than their actual levels of performance. Across three studies in which actual students made predictions about their exam performance in their courses, we demonstrated that students' grade predictions are highly biased by their desired grades on those exams. We obtained this result when students predicted their exam grades over a week before the exam (Study 1), immediately after taking the exam (Study 2), and across the four course exams in a single semester (Study 3). These results are informative for understanding why the "unskilled-and-unaware" pattern of performance predictions occurs, and why people in general tend to be overconfident when making both physical and mental performance predictions. PMID- 27270924 TI - More Questions than Answers: Continued Critical Reanalysis of Fredrickson et al.'s Studies of Genomics and Well-Being. AB - We critically re-examine Fredrickson et al.'s renewed claims concerning the differential relationship between hedonic and eudaimonic forms of well-being and gene expression, namely that people who experience a preponderance of eudaimonic well-being have gene expression profiles that are associated with more favorable health outcomes. By means of an extensive reanalysis of their data, we identify several discrepancies between what these authors claimed and what their data support; we further show that their different analysis models produce mutually contradictory results. We then show how Fredrickson et al.'s most recent article on this topic not only fails to adequately address our previously published concerns about their earlier related work, but also introduces significant further problems, including inconsistency in their hypotheses. Additionally, we demonstrate that regardless of which statistical model is used to analyze their data, Fredrickson et al.'s method can be highly sensitive to the inclusion (or exclusion) of data from a single subject. We reiterate our previous conclusions, namely that there is no evidence that Fredrickson et al. have established a reliable empirical distinction between their two delineated forms of well-being, nor that eudaimonic well-being provides any overall health benefits over hedonic well-being. PMID- 27270925 TI - Combined Racial and Gender Differences in the Long-Term Predictive Role of Education on Depressive Symptoms and Chronic Medical Conditions. AB - BACKGROUND: Despite a well-established literature on the protective effect of education on health, less is known about group differences in the mechanisms underlying this association. Using a life course approach and cumulative advantage theory, this study compared Black men, Black women, White men, and White women to assess the long-term gradient (education as a continuous measure) and threshold (>12 years) effects of baseline education on change in chronic medical conditions (CMC) and depressive symptoms (DS) from baseline to 25 years later. METHODS: Data came from the Americans' Changing Lives Study, 1986-2011. The study followed Black and White respondents for up to 25 years, among whom 1271 individuals who had survived and were under follow-up were interviewed in 2011 and reported their number of chronic medical conditions and depressive symptoms (Center for Epidemiological Studies-Depression; CES-D 11). Multi-group structural equation modeling was used to compare gradient and threshold effects of education on change in chronic medical conditions and depressive symptoms from baseline (1986) to 25 years later (2011) among Black men, Black women, White men, and White women. RESULTS: There were group differences in the long-term association between education measured as a gradient and the change in depressive symptoms and chronic medical conditions during the follow-up, and in the association between education measured at the threshold of 12 years on change in depressive symptoms from baseline to follow-up. However, the association between education measured at this threshold and change in chronic medical conditions did not differ across race-gender groups. With the exception of Black men, who showed a gradient protective effect for baseline education against increase in the number of chronic medical associations (threshold or gradient) with change in chronic medical conditions. Among White men and White women, education had a threshold protective effect against increase in depressive symptoms from baseline to 25 years later. Black men and women showed a gradient protective effect of baseline education against an increase in depressive symptoms over the 25-year follow-up period, but unexpectedly, a threshold effect of education was also found to be associated with an increase in depressive symptoms over the follow-up period among Black men. This finding suggests that although Black men benefit from each incremental increase in education, those who graduated from high school were at an additional risk of depressive symptoms over a 25-year period. CONCLUSION: Findings suggest that the intersection of race and gender influences how education is associated with long-term changes in physical and mental health of individuals from baseline to 25 years later. As the shape of the association between education and health depends on the intersection of race and gender, these groups may vary for operant mechanisms by which education operates as a main social determinant of health. PMID- 27270927 TI - Modification of the Catalytic Properties of Erythrocyte Aldehyde Dehydrogenase in Rats after Nitric Oxide Inhalation. AB - We studied aldehyde dehydrogenase activity in erythrocytes from healthy rats and animals with thermal trauma after NO inhalation. NO had an activating effect on catalytic properties of aldehyde dehydrogenase in healthy rats and burned animals. The effect of NO was more pronounced during burn disease. PMID- 27270926 TI - Anxiolytic, Psychostimulant, and Analgesic Effects of Various Volumes of Ethanol Solution in Different Concentrations, but in the Same Dose. AB - We studied the effect of ethanol (dose 2 g/kg) in various concentrations (5, 13, and 40%) and different volumes (40, 15.5, and 5 ml/kg) on the level of anxiety, locomotor activity, and pain sensitivity in rats. Administration of 40 ml/kg water to animals was followed by a significant increase in the time spent in the open arms of the elevated plus maze. Administration of water in a volume of 5 or 15.5 ml/kg had little effect on the level of anxiety. The greater was the volume of intragastrically administered ethanol, the stronger was the anxiolytic effect. The psychostimulant and analgesic effects of ethanol were more pronounced after administration of medium volumes and intermediate concentrations of ethanol containing solutions. Since administration of these solutions cannot produce maximum blood concentration of ethanol, we believe that the observed effects are mainly related to the direct effect of ethanol on the stomach tissue. PMID- 27270928 TI - Effects of Deep Cooling and Re-Warming on Ionotropic Glutamatergic Receptors In Vitro. AB - We studied the effects of cooling to -10 degrees C and re-warming to 37 degrees C on slices of rat olfactory cortex. The amplitudes of action potential in the lateral olfactory tract and excitatory postsynaptic potential activated by AMPA recovered during slow cooling/re-warming (0.1 degrees C/min), while during rapid cooling/re-warming (9 degrees C/min), they surpassed the control values. NMDA receptor-dependent mechanism was blocked in both cooling/re-warming modes. Swelling of the brain slices was observed during re-warming, especially during rapid cooling/re-warming. Nerve fibers of the lateral olfactory tract and AMPA related processes survived deep cooling/re-warming, while NMDA-related processes were irreversibly blocked. PMID- 27270929 TI - Histoenzymological Characteristics of Smooth Muscle Cells in Myocardial Vessels: A Comparative Study under Conditions of Increased Left or Right Ventricular Afterload. AB - Histoenzymological methods were used to study metabolism of smooth muscle cells of intramural myocardial arteries during experimental aortic or pulmonary artery stenosis. Aortic stenosis was accompanied by changes in smooth muscles of the left ventricle manifested by deceleration of tricarboxylic acid cycle, inhibition of oxidation of free fatty acids and their metabolites, flux redistribution in the glycolytic cascade, and inhibition of shuttle systems and biosynthetic processes. Similar metabolic alterations were observed in vessels of the ventricular septum, but they were not revealed in vessels of the right ventricle (except glycolysis stimulation). Under conditions of pulmonary artery stenosis, histoenzymological alterations in vascular smooth muscle of both ventricles and ventricular septum were similar, which attested to acceleration of tricarboxylic acid cycle, stimulation of oxidation of the free fatty acids with their metabolites, acceleration of glycolysis, and activation of the shuttle systems and biosynthetic processes. Comparative analysis of histoenzymological alterations revealed substantial differences in the character of metabolic changes under conditions of increased left and right ventricular afterload, which can be caused by peculiarities in myocardial blood flow, severity of circulatory disorders, severity of hypoxia, and intensity of processes maintaining ionic homeostasis in vascular smooth muscles and transport across the histohematic barriers. The data attest to important metabolic role of glycolysis in vascular smooth muscles of the myocardium, especially under conditions of enhanced afterload of the right ventricle. PMID- 27270930 TI - Cell Composition of Central and Peripheral Lymphoid Organs of Wistar Rats Treated with a Biomedical Cell Product. AB - We studied the effect of a biomedical cell product (bone marrow multipotent mesenchymal stromal cells and products secreted by these cells in conditioned medium) on subpopulation composition of lymphoid cells of central and peripheral lymphoid organs of Wistar rats under normal conditions. Changes in the subpopulation composition of lymphoid organs depended on the route of administration of biomedical cell product. PMID- 27270931 TI - Analysis of the Relationship between Antioxidant Enzyme Gene Polymorphisms and Their Activity in Post-Traumatic Gonarthrosis. AB - Analysis of polymorphisms of genes encoding antioxidant enzymes SOD1 (G7958A), SOD2 (T58C), CAT (C-262T), and GSTP1 (Ile105Val) in 93 patients with post traumatic gonarthrosis showed that GSTP1 Ile105Val polymorphism is often associated with heterozygous mutation in catalase gene CAT C-262T. In gonarthrosis, catalase activity in peripheral blood mononuclear cells in patients with CT genotype of the C-262T locus of CAT gene more than 2-fold surpassed that in CC genotype and more than 50% surpassed the normal. Changes in the balance of activity of antioxidant enzymes can affect viability of mononuclear cells. PMID- 27270932 TI - Association of the HindIII Lipoprotein Lipase Gene Polymorphism with the Development of the Non-Biliary Acute Pancreatitis: a Pilot Study. AB - We studied the relationship between lipoprotein lipase (LPL) gene HindIII polymorphism and the development of acute pancreatitis in the Russian population. Whole blood samples were collected from 145 patients with acute non-biliary pancreatitis and 191 healthy individuals. Genotyping of LPL gene HindIII (rs320) polymorphism was performed by PCR with TaqMan assay. It was found that allele H+ (OR=0.63, 95%CI 0.41-0.96, p=0.03) and genotype H+/H+ (OR=1.79, 95%CI 1.06-3.04, p=0.03) were associated with the risk of acute non-biliary pancreatitis only in males. In this study, the relationship between HindIII polymorphism of LPL gene with the risk of acute non-biliary pancreatitis was revealed. PMID- 27270934 TI - Application of Laser Correlation Spectroscopy for Measuring Virus Size. AB - Dynamic light scattering method or laser correlation spectroscopy was applied to evaluation of the size of viruses. We measured correlation functions of the light scattered by human immunodeficiency viruses (HIV) and hepatitis A viruses (HAV) and found that size of HIV-1 (subtype A and B) and HAV virions were 104 nm and 28 nm, respectively. Comparison of these findings with electron microscopy data for fixed samples of the same viruses showed good agreement of the results. PMID- 27270933 TI - New Genetic Constructs for Generation of Stable Therapeutic Antibodies to Organophosphorus Toxins in Methylotrophic Yeasts Pichia Pastoris. AB - We propose a new method of obtaining of stable Fab-fragments of antibodies in Pichia pastoris expression system. Recently, we obtained Fab-fragments of antibodies neutralizing organophosphorus toxins. However, high yield of the target products was not attained because of high level of proteolytic degradation. In the present study, we identified sites of proteolytic degradation in Fab-fragments and endogenous proteases performing degradation, which allowed obtaining optimized genetic constructs for expression of antibody heavy chains (IgGgamma1) and kappa and lambda isotypes of light chains. Co-transformation of these vectors allowed obtaining Fab-fragments of antibodies to organophosphorus toxins without proteolytic degradation of the product. PMID- 27270935 TI - Age-Related Changes in the System Metalloproteinases/Tissue Metalloproteinase Inhibitors and Proteoglycan Components in Mouse Organs. AB - Activity of MMP and content of TIMP and some proteoglycan components were measured in the liver, lungs, and spleen of BALB/c mice aging 2, 6, and 12 months. The increase in the content of proteoglycan components in mouse organs was associated with age-related changes in MMP activity and TIMP-1 and TIMP-2 levels. The ratio between MMP activity and content of TIMP-1 and TIMP-2 differed in the studied organs. The levels of TIMP-1 and TIMP-2 in mouse blood serum and their concentration in studied organs changed asynchronously with age. They are important regulators that determine MMP activity in the analyzed age periods in mice, which can be determined as periods of growth, development, and ageing. PMID- 27270936 TI - Studying the Effect of a Composition of the Cluster Core in High-Radiopacity Cluster Complexes of Rhenium on Their Acute Toxicity In Vivo. AB - An in vivo study was performed to evaluate the dependence of acute toxicity of high-radiopacity and luminescent octahedral cluster complexes of rhenium after intravenous injection on a composition of the cluster core. Changes in mouse body weight, water and food consumption, degree of intoxication, and morphological changes in the visceral organs were studied after intravenous injection of the following cluster complexes with various internal ligands (S, Se, or Te): Na4[{Re 6 Te 8 }(CN)6], Na4[{Re 6 Se 8 }(CN)6], and Na4[{Re 6 S 8 }(CN)6]. The Na4[{Re 6 S 8 } (CN)6] cluster complex was shown to be the safest for animals. PMID- 27270937 TI - Quantitative Evaluation of Primordial Follicles in Rat Ovaries during the Early and Delayed Terms after Different Cytostatic Exposures. AB - Experiments on female Wistar rats showed that cytostatic agents (farmorubicin, platidiam, carboplatin, and etoposide) induce an initial significant decrease in the number of primordial follicles. Over the next 2-3 estrous cycles after administration of farmorubicin, platidiam, and carboplatin, this index practically did not differ from the control. The number of primordial follicles in the third and fourth estrous cycles after farmorubicin administration, as well as in the second and sixth estrous cycles after etoposide administration was much higher than the follicular reserve after cytostatic treatment (first estrous cycle). The ovarian reserve was exhausted in the delayed period after the start of the experiment. This dynamics of the pool of primordial follicles suggests that the ovary of rats in the postnatal period of life contains a limited number of female germline stem cells. PMID- 27270938 TI - Peptidyl Aldehyde Specifically Interacts with Immunosubunit beta1i Proteasome: In Vitro and In Vivo Effects. AB - We studied the effect of beta1i-specific peptidyl aldehyde IPSI-001 on proteasome from mammalian cells. In concentrations <1 MUM, this agent effectively suppressed immunoproteasome, but only slightly reduced chymotrypsin-like activity of constitutive proteasome. Intraperitoneal administration of this inhibitor to C3H/He mice in a dose of 100 mg/kg induced no significant physiological or behavioral changes, which attested to its considerable therapeutic potential in the treatment of autoimmune neurodegenerative pathologies. PMID- 27270939 TI - Study of Fibronectin Type III-Like Domains Role in Activation of gp130 Receptor. AB - Chimeric gp130 receptors were produced to study the role of three fibronectin type III-like domains in activation of gp130 receptor machinery. The ligand induced dimerization of gp130 was sufficient to trigger STAT3 signaling pathway. These findings can be used as the basis in designing novel therapeutic gp130 inhibitors. PMID- 27270940 TI - Relationships between Mechanical Nociceptive Threshold and Activity of Antioxidant Enzymes in Male Rats with Experimental Type I Diabetes Mellitus. AB - We analyzed the dynamics of neuropathic pain development and changes in catalase and superoxide dismutase (SOD) activities in the brain, liver, and skeletal muscles of male Wistar rats with 1-month streptozotocin-induced diabetes mellitus. A decrease in mechanical nociceptive threshold was revealed that progressed during the disease progress. Insulin treatment restored nociceptive threshold in diabetic animals to the control values. Catalase activity in the liver and skeletal muscles of diabetic rats increased by 1.5 and 2 times, respectively, in comparison with the control, while insulin treatment reduced enzyme activity to the control level. In the brain, catalase activity was reduced by 1.5 times and insulin therapy did affect this parameter. SOD activity in the studied tissues remained unchanged during diabetes and was not affected by insulin therapy. A strong negative correlation between nociceptive threshold in rats and catalase activity in their liver and skeletal muscles was found. PMID- 27270941 TI - Ketamine-Midazolam Anesthesia Induces Total Inhibition of Cortical Activity in the Brain of Newborn Rats. AB - The effects of general anesthetics ketamine and midazolam, the drugs that cause neuroapoptosis at the early stages of CNS development, on electrical activity of the somatosensory cortex in newborn rats were studied using extracellular recording of local field potentials and action potentials of cortical neurons. Combined administration of ketamine (40 mg/kg) and midazolam (9 mg/kg) induced surgical coma and almost completely suppressed early oscillatory patterns and neuronal firing. These effects persisted over 3 h after injection of the anesthetics. We concluded that general anesthesia induced by combined administration of ketamine and midazolam profoundly suppressed cortical activity in newborn rats, which can trigger neuroapoptosis in the developing brain. PMID- 27270942 TI - Role of beta-Adrenoceptors and L-Type Ca(2+)-Channels in the Mechanism of Reperfusion-Induced Heart Injury. AB - We studied the effects of beta-adrenoceptor antagonists propranolol and nadolol and L-type Ca(2+)-channel blocker verapamil on cardiac reperfusion injury developed after 45-min coronary occlusion. The substances were injected intravenously 5 min before reperfusion. The results indicate that activation of beta-adrenoceptors and opening of L-type Ca(2+)-channels promote the development of cardiac reperfusion injury, while blockage of beta-adrenoceptors and/or L-type Ca(2+)-channels prevents reoxygenation-induced myocardial injury. Propranolol, nadolol, and verapamil can produce infraction-limiting effects after onset of ischemic heart injury. PMID- 27270943 TI - Induction of the Adaptive Response in Mice Exposed to He-Ne Laser and X-Ray Radiation. AB - We studied the dose-dependent induction of in vivo adaptive response in the bone marrow and blood of mice exposed to low-intensity radiation of He-Ne laser (633 nm) and X-ray radiation by the severity of cytogenetic injury and intensity of ROS production, respectively. Induction of the adaptive response in mice preexposed to He-Ne laser and X-ray radiation depended on the adaptive dose and the interval between the adaptive and main doses and correlated with changes in ROS generation. The adaptive response after exposure to low-intensity ionizing and non-ionizing radiation was observed in the same dose range, which attests to similar mechanisms of its induction. PMID- 27270944 TI - Influence of Reduced Graphene Oxide on Effective Absorption Bandwidth Shift of Hybrid Absorbers. AB - The magnetic nanoparticle composite NiFe2O4 has traditionally been studied for high-frequency microwave absorption with marginal performance towards low frequency radar bands (particularly L and S bands). Here, NiFe2O4 nanoparticles and nanohybrids using large-diameter graphene oxide (GO) sheets are prepared via solvothermal synthesis for low-frequency wide bandwidth shielding (L and S radar bands). The synthesized materials were characterized using XRD, SEM, FTIR and microwave magneto dielectric spectroscopy. The dimension of these solvothermally synthesized pristine particles and hybrids lies within 30-58 nm. Microwave magneto-dielectric spectroscopy was performed in the low-frequency region in the 1 MHz-3 GHz spectrum. The as-synthesized pristine nanoparticles and hybrids were found to be highly absorbing for microwaves throughout the L and S radar bands (< -10 dB from 1 MHz to 3 GHz). This excellent microwave absorbing property induced by graphene sheet coupling shows application of these materials with absorption bandwidth which is tailored such that these could be used for low frequency. Previously, these were used for high frequency absorptions (typically > 4 GHz) with limited selective bandwidth. PMID- 27270945 TI - Characterization and Complete Genome Sequences of Three N4-Like Roseobacter Phages Isolated from the South China Sea. AB - Three bacteriophages (RD-1410W1-01, RD-1410Ws-07, and DS-1410Ws-06) were isolated from the surface water of Sanya Bay, northern South China Sea, on two marine bacteria type strains of the Roseobacter lineage. These phages have an isometric head and a short tail, morphologically belonging to the Podoviridae family. Two of these phages can infect four of seven marine roseobacter strains tested and the other one can infect three of them, showing relatively broader host ranges compared to known N4-like roseophages. One-step growth curves showed that these phages have similar short latent periods (1-2 h) but highly variable burst sizes (27-341 pfu cell(-1)). Their complete genomes show high level of similarities to known N4-like roseophages in terms of genome size, G + C content, gene content, and arrangement. The morphological and genomic features of these phages indicate that they belong to the N4likevirus genus. Moreover, comparative genomic analysis based on 43 N4-like phages (10 roseobacter phages and 33 phages infecting other lineages of bacteria) revealed a core genome of 18 genes shared by all the 43 phages and 38 genes shared by all the ten roseophages. The 38 core genes of N4 like roseophages nearly make up 70 % of each genome in length. Phylogenetic analysis based on the concatenated core gene products showed that our phage isolates represent two new phyletic branches, suggesting the broad genetic diversity of marine N4-like roseophages remains. PMID- 27270946 TI - Internal mammary artery perforator propeller flap for contralateral mastectomy defect: A case report. AB - The internal mammary artery perforator (IMAP) flap can be used as either loco regional or free flap, and provides thin flexible coverage for defects of the chest wall and cervical regions. In this report, we present a bilateral mastectomy case in which the left mastectomy defect was closed with an IMAP propeller flap harvested from the right breast. Our patient with a history of left breast conservation therapy was diagnosed invasive ductal carcinoma in her left breast 14 years later. On physical examination, the patient's left breast displayed the stigmata of radiotherapy including dark discoloration and firmness to palpation, compared to contralateral pendulous breast. After bilateral mastectomy, an IMAP flap with a size of 26 cm * 11 cm was harvested from right chest and was transposed 180 degrees clockwise in a propeller fashion to the left mastectomy defect without any tension. The flap survived without any complication and the patient was free of recurrence or metastases during the follow-up of 18 months. The patient was satisfied with the outcome. IMAP propeller flap could be harvested safely to the anterior axillary fold in the subcutaneous fat plane. It may provide a large skin paddle especially in large breasted women. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:507-510, 2016. PMID- 27270947 TI - Papillary carcinoma of the breast: diagnostic agreement and management implications. AB - AIMS: Papillary carcinoma (PC), which is a rare type of breast cancer, comprises a heterogeneous group of tumours. The diagnostic categorization of PC as in-situ and invasive disease remains a matter of debate with respect to interpretation of its overlapping histological features, and with respect to the uncertainty in clinical behaviour that this dilemma raises. The aim of this study was to assess the diagnostic agreement regarding PC among reporting breast pathologists. METHODS AND RESULTS: Six cases of PC included in the UK National Health Service Breast Screening Programme breast pathology interpretive external quality assurance scheme in the last 10 years were reviewed. In this scheme, one representative haematoxylin and eosin-stained slide from each case is circulated to an average of 600 participants. Data on diagnostic categories were collected and slides were reviewed according to the World Health Organization (WHO) diagnostic criteria. The number of final diagnoses of malignancy (in situ or invasive) was highest for invasive PC (99% of the participants diagnosed it as malignant), followed by solid PC (94% and 95%, respectively), encapsulated PC (92% and 92%, respectively), and papillary ductal carcinoma in situ (DCIS) (88%). Most cases of papillary DCIS were correctly classified as in-situ disease (77%), but 28% of the participants classified invasive PC cases as in-situ disease. Of the participants, 24% reported encapsulated PC as invasive disease. Of the two solid PC cases, one showed some features consistent with the WHO description of invasive solid PC, whereas the other showed features of classic (non-invasive) solid PC. Both cases were reported as invasive by 75% and 77% of participants, respectively. Breast specialists more frequently classified PC as an in-situ carcinoma than did non-specialist participants, and the difference was significant (P = 0.013). CONCLUSIONS: Recognition of PC as a malignant entity (in situ or invasive) is high, but concordance of its classification into in-situ and invasive disease is low. Histological features that can define invasion in PC should be better defined. These rare lesions require additional diagnostic work up, and difficult cases should trigger consensus opinion or expert referral. PMID- 27270949 TI - "Morphology's intention is to portray rather than explain". PMID- 27270948 TI - Caffeine, a common active adulterant of cocaine, enhances the reinforcing effect of cocaine and its motivational value. AB - RATIONALE: Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. OBJECTIVES: We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. METHODS: In naive rats, we assessed (1) the ability of the cocaine (0.250-0.125 mg/kg/infusion) and caffeine (0.125-0.0625 mg/kg/infusion) combination to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine or caffeine alone and (2) the effect of caffeine (0.0625 mg/kg/infusion) in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. RESULTS: Cocaine combined with caffeine and cocaine alone was self administered on FR and PR schedules of reinforcement. Interestingly, the breaking point determined for the cocaine + caffeine group was significantly higher than the cocaine group. Moreover, caffeine, that by itself did not maintain self administration behavior in naive rats, maintained drug-seeking behavior of rats previously exposed to combinations of cocaine + caffeine. CONCLUSIONS: Caffeine enhances the reinforcing effects of cocaine and its motivational value. Our results highlight the role of active adulterants commonly used in cocaine-based illicit street drugs. PMID- 27270950 TI - Comparisons of pharmacokinetics and NO-releasing of nitrofibriate and fenofibrate after oral administration in rats. AB - Nitrofibriate, a new compound of hypolipidemic, is modified based on fenofibrate. Both of them are used for prevention and treatment of cardiovascular diseases. In this study, an accurate and sensitive analytical method of reversed-phase high performance liquid chromatography was developed to determine fenofibric acid, which is an active metabolite of both nitrofibriate and fenofibrate in rat plasma. This method was validated and successfully applied to pharmacokinetic study of nitrofibriate and fenofibrate after oral administration. The results suggested that the pharmacokinetic behavior of nitrofibriate followed a nonlinear process, while fenofibrate was linear, demonstrating that the two drugs were different in pharmacokinetic behaviors. Moreover, the effect of fenofibrate and nitrofibriate on releasing NO in rat serum was explored. This study showed that nitrofibriate, as a nitric oxide donor, could slowly release nitric oxide in vivo. This study provided a biopharmaceutical basis for further study of nitrofibriate. PMID- 27270952 TI - Silver(i) complexes with 1'-(diphenylphosphino)-1-cyanoferrocene: the art of improvisation in coordination. AB - 1'-(Diphenylphosphino)-1-cyanoferrocene () reacts with silver(i) halides at a 1 : 1 metal-to-ligand ratio to afford the heterocubane complexes [Ag(MU3-X)( kappaP)]4, where X = Cl (), Br (), and I (). In addition, the reaction with AgCl with 2 equiv. of leads to chloride-bridged dimer [(MU-Cl)2{Ag(-kappaP)2}2] () and, presumably, also to [(MU(P,N)-){AgCl(-kappaP)}]2 (). While similar reactions with AgCN furnished only the insoluble coordination polymer [( kappaP)2Ag(NC)Ag(CN)]n (), those with AgSCN afforded the heterocubane [Ag( kappaP)(MU-SCN-S,S,N)]4 () and the thiocyanato-bridged disilver(i) complex [Ag( kappaP)2(MU-SCN-S,N)]2 (), thereby resembling reactions in the AgCl- system. Attempted reactions with AgF led to ill-defined products, among which [Ag( kappaP)2(MU-HF2)]2 () and [(MU-SiF6){Ag(-kappaP)2}2] () could be identified. The latter compound was prepared also from Ag2[SiF6] and . Reactions between and AgClO4 or Ag[BF4] afforded disilver complexes [(MU(P,N)-)Ag(ClO4-kappaO)]2 () and [(MU(P,N)-)Ag(BF4-kappaF)]2 () featuring pseudolinear Ag(i) centers that are weakly coordinated by the counter anions. A similar reaction with Ag[SbF6] followed by crystallization from ethyl acetate produced an analogous complex, albeit with coordinated solvent, [(MU(P,N)-)Ag(AcOEt-kappaO)]2[SbF6]2 (). Ultimately, a compound devoid of any additional ligands at the Ag(i) centers, [(MU(P,N)-)Ag]2[B(C6H3(CF3)2-3,5)4]2 (), was obtained from the reaction of with silver(i) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. The reaction of Ag[BF4] with two equivalents of produced unique coordination polymer [Ag(-kappaP)(MU(P,N) )]n[BF4]n (), the structure of which contained one of the phosphinoferrocene ligands coordinated as a P,N-chelate and the other forming a bridge to an adjacent Ag(i) center. All of these compounds were structurally characterized by single-crystal X-ray crystallography, revealing that the lengths of the bonds between silver and its anionic ligand(s) typically exceed the sum of the respective covalent radii, which is in line with the results of theoretical calculations at the density-functional theory (DFT) level, suggesting that standard covalent dative bonds are formed between silver and phosphorus (soft acid/soft base interactions) while the interactions between silver and the ligand's nitrile group (if coordinated) or the supporting anion are of predominantly electrostatic nature. PMID- 27270951 TI - Molecular distributions and compound-specific stable carbon isotopic compositions of lipids in wintertime aerosols from Beijing. AB - Molecular distributions and stable carbon isotopic compositions (delta(13)C) of n alkanes, fatty acids and n-alcohols were investigated in urban aerosols from Beijing, northern China to better understand the sources and long-range atmospheric transport of terrestrial organic matter during polluted and clear days in winter. n-Alkanes (C19-C36), fatty acids (C8-C32) and n-alcohols (C16 C32) detected in Beijing aerosols are characterized by the predominance of C23, C16 and C28, respectively. Carbon preference index (CPI) values of n-alkanes, the ratios of the sum of odd-numbered n-alkanes to the sum of even-numbered n alkanes, are close to 1, indicating a heavy influence of fossil fuel combustion. Relatively higher ratios of C(18:0+16:0)/C(18:n+16:1) (fatty acids) on clear days than polluted days indicate that long-distance transport and/or photochemical aging are more significant during clear days. delta(13)C values of n-alkanes and low molecular weight fatty acids (C16:0, C18:0) ranged from -34.1 to -24.7% and 26.9 to -24.6%, respectively, which are generally heavier on polluted days than those on clear days. Such a wide range suggests that atmospheric lipids in Beijing aerosols originate from multiple sources and encounter complicated atmospheric processes during long-range transport in North China. PMID- 27270954 TI - [Improvement of the diagnostic accuracy in patients with suspected rheumatic disease by preselection in the early arthritis clinic : An alternative to the appointment service point model of the Healthcare Improvement Act]. AB - The diagnosis and treatment of inflammatory rheumatic diseases can be delayed by a long waiting period for an appointment with a rheumatologist. This study investigated whether preselection of patients in an early arthritis clinic is a suitable tool to improve this situation. In 2006 an early arthritis clinic was founded by the Collaborating Center of Rheumatology in Halle (Saale). General practitioners refer patients by using a special registration form that helps to identify patients with an early joint swelling or inflammatory back pain. Patients are then allocated to a pool of participating rheumatologists and are seen by one of them within 2 weeks. For our scientific evaluation the data of 248 patients from the early arthritis clinic and data of 187 regular patients were gathered by means of an additional questionnaire for rheumatologists and patients. In the early arthritis clinic 40.3 % of patients received the diagnosis of an inflammatory rheumatic disease compared with 19.3 % in the control group. In the latter group 51 % were diagnosed as having degenerative joint or spine disorders compared with 22 % in patients from the early arthritis clinic; however, 61 % of patients who were referred to the early arthritis clinic did not fulfill the criteria of the registration form. On the other hand, patients in this group fulfilling these criteria had an inflammatory rheumatic disease in 68.1 % of the cases. The mean duration of symptoms at the time of first rheumatological consultation was significantly shorter in the early arthritis clinic than in the control group (6 vs. 39 months). Our data demonstrate that the preselection of patients can serve as a useful instrument to guide the referral of patients to rheumatologists. The high percentage of patients who did not fulfil the criteria of the registration form indicates that a further improvement of this form is necessary and stresses the need for intensive communication between rheumatologists and general practitioners. Early arthritis clinics may be an alternative to the current efforts of the legislative authorities to improve specialist care by centralized distribution of specialist appointments. PMID- 27270955 TI - [Not Available]. PMID- 27270956 TI - Using low-energy near infrared light and upconverting nanoparticles to trigger photoreactions within supramolecular assemblies. AB - This overview highlights how the high-energy ultraviolet or visible light required to drive photochemical reactions can be overcome by integrating the chromophores into supramolecular structures containing upconverting nanoparticles with trivalent lanthanide dopants (such as Tm(3+) and Er(3+)). These nanoparticles are particularly interesting systems because they absorb multiple photons of near infrared light and convert them into higher-energy light which is emitted in the ultraviolet and visible regions of the electromagnetic spectrum. The upconverting nanoparticles effectively act as nanoscopic 'light bulbs', and in this way, less damaging near infrared light can be used to trigger photochemical reactions for use in imaging and small molecule release. Several examples of how this phenomenon is being used in photochemistry will be presented with the focus being on self-assembled supramolecular systems, some of which are being used in cells and small animals. PMID- 27270953 TI - STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells. AB - Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS. PMID- 27270957 TI - Improving the performance of surgery-based clinical pathways: a simulation optimization approach. AB - This paper aims to improve the performance of clinical processes using clinical pathways (CPs). The specific goal of this research is to develop a decision support tool, based on a simulation-optimization approach, which identify the proper adjustment and alignment of resources to achieve better performance for both the patients and the health-care facility. When multiple perspectives are present in a decision problem, critical issues arise and often require the balancing of goals. In our approach, meeting patients' clinical needs in a timely manner, and to avoid worsening of clinical conditions, we assess the level of appropriate resources. The simulation-optimization model seeks and evaluates alternative resource configurations aimed at balancing the two main objectives meeting patient needs and optimal utilization of beds and operating rooms.Using primary data collected at a Department of Surgery of a public hospital located in Genoa, Italy. The simulation-optimization modelling approach in this study has been applied to evaluate the thyroid surgical treatment together with the other surgery-based CPs. The low rate of bed utilization and the long elective waiting lists of the specialty under study indicates that the wards were oversized while the operating room capacity was the bottleneck of the system. The model enables hospital managers determine which objective has to be given priority, as well as the corresponding opportunity costs. PMID- 27270958 TI - Adapting clinical gamma cameras for body monitoring in the event of a large-scale radiological incident. AB - After a release of radionuclides, accidental or otherwise, there will be an urgent need to identify members of the general public who have received a significant intake of radioactive material, sufficient to require medical treatment or further investigation. A large number of people could be contaminated in such an incident. For gamma-ray emitting radionuclides this screening could be carried out using gamma camera medical imaging systems, such as those that are present in many large UK hospital sites. By making a number of simple reversible changes such as removal of collimators, these cameras could be employed as useful additional screening instruments as well as an aid in contamination control. A study was carried out to investigate which systems were present in sufficient number to offer wide scale coverage of UK population centres. Nine gamma cameras (eight dual head and one single head) were assessed using point source and bottle mannequin (BOMAB) phantom measurements so that a mathematical model could be developed for use with the MCNPX Monte Carlo radiation transport code. The gamma camera models were assessed for practical seated and supine geometries to give calibration factors for a list of target radionuclides that could be released in a radiological incident. The minimum detectable activities (MDAs) that were achieved for a five minute measurement demonstrated that these systems are sufficiently sensitive to be used for screening of the general public and are comparable to other body monitoring facilities. While gamma cameras have on-board software that are designed for imaging and provide for a gamma-ray energy range suitable for radionuclides for diagnostic imaging (such as 99mTc), they are not as versatile as custom-built body monitoring systems. PMID- 27270959 TI - Edible Cannabis Products: It Is Time for FDA Oversight. PMID- 27270961 TI - Prevalence of Artificial Food Colors in Grocery Store Products Marketed to Children. AB - Artificial food colors (AFCs) in foods and beverages may be harmful to children. This study assesses the percentage of grocery store products marketed to children that contain AFCs, by category and company. The research team collected product and food-color information about 810 products in one grocery store in North Carolina in 2014. Overall, 350 products (43.2%) contained AFCs. The most common AFCs were Red 40 (29.8% of products), Blue 1 (24.2%), Yellow 5 (20.5%), and Yellow 6 (19.5%). Produce was the only category that did not have any AFCs. The highest percentage of products with AFCs was found in candies (96.3%), fruit flavored snacks (94%), and drink mixes/powders (89.7%). Forty-one of the 66 companies marketed products containing AFCs. Given concerns about health effects of AFCs and high proportions of high-AFC categories, clinicians, parents, food companies, and the government can take steps to support children's healthy eating and development by reducing AFCs in children's diets. PMID- 27270960 TI - Gingival Toll-like receptor and cytokine messenger RNA levels in equine periodontitis and oral health. AB - REASONS FOR PERFORMING STUDY: Equine periodontitis is a common and painful condition. However, the disease often goes unnoticed by owners and is thus a major welfare concern. The aetiopathogenesis of the condition remains poorly understood and has been investigated in few studies. The innate immune system is known to play an important role in human periodontitis, but its role in equine periodontitis has not been examined. OBJECTIVES: To quantify the messenger (m)RNA levels of Toll-like receptors (TLRs) and cytokines in gingival tissue from orally healthy horses and those affected by periodontitis. STUDY DESIGN: Observational study. METHODS: Gingival tissue samples were taken post-mortem from 13 horses with no clinical signs of oral disease and 20 horses with periodontitis. mRNA levels of TLR2, TLR4 and TLR9 and cytokines interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), IL-4, IL-6, IL-10, IL-12, IL-17 and interferon gamma (IFN-gamma) were determined using quantitative real-time PCR. The statistical significance of results was assessed using appropriate t tests. RESULTS: mRNA levels of all TLRs and cytokines were upregulated in equine periodontitis. Significant increases in mRNA levels of TLR2, TLR9, IL-4, IL-10, IL-12 (P<=0.05) and IFN-gamma (P<=0.01) were observed for both unweighted and age weighted analyses of diseased gingival tissue samples compared with healthy gingival samples. In comparisons of samples of periodontitis lesions with healthy gingival control samples from the same horse, significant increases in mRNA levels of TLR4, TLR9, IL-10, IFN-gamma (P<=0.05), TLR2, IL-1beta and IL-12p35 (P<=0.01) were observed. CONCLUSIONS: This study has provided an initial insight into the involvement of the immune system in equine periodontitis. Increased mRNA levels of TLR2, TLR4 and TLR9 indicate substantial microbial challenge in diseased gingival tissue. A mixed Th1/Th2/Th17 cytokine response is produced in equine periodontitis. Further studies are required to more fully characterise the role of the innate immune system in this disease. PMID- 27270962 TI - Including Youth Violence Screening on Previsit Questionnaires and the Effect on Other Health Risk Behavior Discussions. PMID- 27270963 TI - Acoustic sensor versus electrocardiographically derived respiratory rate in unstable trauma patients. AB - Respiratory rate (RR) is important in many patient care settings; however, direct observation of RR is cumbersome and often inaccurate, and electrocardiogram derived RR (RRECG) is unreliable. We asked how data derived from the first 15 min of RR recording after trauma center admission using a novel acoustic sensor (RRa) would compare to RRECG and to end-tidal carbon dioxide-based RR ([Formula: see text]) from intubated patients, the "gold standard" in predicting life-saving interventions in unstable trauma patients. In a convenience sample subset of trauma patients admitted to our Level 1 trauma center, enrolled in the ONPOINT study, and monitored with RRECG, some of whom also had [Formula: see text] data, we collected RRa using an adhesive sensor with an integrated acoustic transducer (Masimo RRaTM). Using Bland-Altman analysis of area under the receiver operating characteristic (AUROC) curves, we compared the first 15 min of continuous RRa and RRECG to [Formula: see text] and assessed the performance of these three parameters compared to the Revised Trauma Score (RTS) in predicting blood transfusion 3, 6, and 12 h after admission. Of the 1200 patients enrolled in ONPOINT from December 2011 to May 2013, 1191 had RRECG data recorded in the first 15 min, 358 had acoustic monitoring, and 14 of the latter also had [Formula: see text]. The three groups did not differ demographically or in mechanism of injury. RRa showed less bias (0.8 vs. 6.9) and better agreement than RRECG when compared to [Formula: see text]. At [Formula: see text] 10-29 breaths per minute, RRa was more likely to be the same as [Formula: see text] and assign the same RTS. In predicting transfusion, features derived from RRa and RRECG gave AUROCs 0.59-0.66 but with true positive rate 0.70-0.89. RRa monitoring is a non-invasive option to glean valid RR data to assist clinical decision making and could contribute to prediction models in non-intubated unstable trauma patients. PMID- 27270964 TI - Tuning the energetics and tailoring the optical properties of silver clusters confined in zeolites. AB - The integration of metal atoms and clusters in well-defined dielectric cavities is a powerful strategy to impart new properties to them that depend on the size and geometry of the confined space as well as on metal-host electrostatic interactions. Here, we unravel the dependence of the electronic properties of metal clusters on space confinement by studying the ionization potential of silver clusters embedded in four different zeolite environments over a range of silver concentrations. Extensive characterization reveals a strong influence of silver loading and host environment on the cluster ionization potential, which is also correlated to the cluster's optical and structural properties. Through fine tuning of the zeolite host environment, we demonstrate photoluminescence quantum yields approaching unity. This work extends our understanding of structure property relationships of small metal clusters and applies this understanding to develop highly photoluminescent materials with potential applications in optoelectronics and bioimaging. PMID- 27270965 TI - Safecast: successful citizen-science for radiation measurement and communication after Fukushima. AB - The Fukushima Daichi Nuclear Power Plant disaster, which began on 11 March 2011, provided a crucial opportunity to evaluate the state of preparation on the part the powerplant operator (TEPCO), relevant Japanese government agencies, and international oversight bodies, to gather necessary information on radiation risks quickly and to share it with those tasked with emergency response as well as with the general public. The inadequacy of this preparation and the chaotic nature of inter-agency and inter-governmental communication has been well noted in several official reports on the disaster. In response, Safecast, an international, volunteer-based organization devoted to monitoring and openly sharing information on environmental radiation and other pollutants, was initiated on 12 March 2011, one day following the start of the accident. Since then the group has implemented participatory, open-source, citizen-science centered radiation mapping solutions developed through a process of collaborative open innovation. The information Safecast provided has proven useful to experts, to policy makers, and to the public. This paper briefly describes the methodology and toolsets Safecast has developed and deployed, as well as organizational and social aspects, and summarizes key results obtained to date. In addition, it discusses appropriate criteria for evaluating the success of citizen-science efforts like Safecast, and places it in context with other non-governmental radiation monitoring efforts. PMID- 27270966 TI - Periostin Deficiency Causes Severe and Lethal Lung Injury in Mice With Bleomycin Administration. AB - Pulmonary capillary leakage followed by influx of blood fluid into the air space of lung alveoli is a crucial step in the progression of acute lung injury (ALI). This influx is due to increased permeability of the alveolar-capillary barrier. The extracellular matrix (ECM) between the capillary and the epithelium would be expected to be involved in prevention of the influx; however, the role of the ECM remains to be addressed. Here, we show that the ECM architecture organized by periostin, a matricellular protein, plays a pivotal role in the survival of bleomycin-exposed mice. Periostin was localized in the alveolar walls. Although periostin-null mice displayed no significant difference in lung histology and air blood permeability, they exhibited early lethality in a model of bleomycin induced lung injury, compared with their wild-type counterparts. This early lethality may have been due to increased pulmonary leakage of blood fluid into the air space in the bleomycin-exposed periostin-null mice. These results suggest that periostin in the ECM architecture prevents pulmonary leakage of blood fluid, thus increasing the survival rate in mice with ALI. Thus, this study provides an evidence for the protective role of the ECM architecture in the lung alveoli. PMID- 27270967 TI - Cell and Tissue Display: An Alternative Multipurpose Tool for Microscopy. AB - We developed a method, termed Cell and Tissue Display (CTD), for embedding 16 or more different tissue samples in multi-compartment agarose blocks. The CTD generated blocks allow uniform multiplexing of cell lines and small tissue fragments within a single histologic block. The distribution of individual cells within the CTD blocks is improved, likely because the individual agarose compartments are small and uniform. The composition of each CTD block can be customized based on intended use. Some potential uses of CTD histologic blocks include improved sectioning of small tissue fragments, such as needle biopsy specimens or punch biopsies; multiplexing of tissue fragments within a single block; and the generation of control slides for laboratory proficiency testing. . PMID- 27270968 TI - Prucalopride induces high-amplitude propagating contractions in the colon of patients with chronic constipation: a randomized study. AB - BACKGROUND: This study compared prucalopride, a selective, prokinetic, 5-HT4 receptor agonist, with polyethylene glycol 3350 + electrolytes (PEG3350), an osmotic laxative, on colonic motility parameters, primarily high-amplitude propagating contractions (HAPCs) in patients with chronic constipation. METHODS: This randomized, cross-over, reader-blinded study was conducted at a single site in the USA. The study was open to men and women aged 18-75 years who met study inclusion criteria. Colonic manometry catheters were inserted the day before investigation. On the investigation days, patients received oral 2 mg prucalopride or 2 * 13.8 g PEG3350 in solution. The primary endpoint was HAPC count (threshold: mean amplitude >=100 mmHg, propagation >=20 cm [HAPC1 ]) in the 12 h after treatment administration. Analyses were also conducted at two co primary thresholds: mean amplitude >=75 mmHg, propagation >=20 cm (HAPC2 ); and mean amplitude >=75 mmHg, propagation >=10 cm (HAPC3 ). Secondary endpoints included HAPC area under the curve (AUC), contraction force, amplitude, duration, and propagation velocity. KEY RESULTS: Thirteen women were enrolled, with 12 completing the study. Significantly more HAPC1 (8.7 +/- 2.06 vs 2.9 +/- 2.06; p = 0.012) and HAPC2 (9.0 +/- 2.11 vs 3.3 +/- 2.11; p = 0.017) were observed in the 12-h periods with prucalopride than with PEG3350. Prucalopride significantly increased mean propagation distance and velocity (HAPC2 ) and mean AUC, force, and amplitude (HAPC3 ) compared with PEG3350. Adverse events were mild or moderate. CONCLUSIONS & INFERENCES: Prucalopride was superior to PEG3350 in inducing HAPCs in patients with chronic constipation. ClinicalTrials.gov number NCT01707667. PMID- 27270969 TI - Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring. AB - Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies. PMID- 27270971 TI - Nuclear and mitochondrial DNA in blastocoele fluid and embryo culture medium: evidence and potential clinical use. AB - The ability to screen embryos for aneuploidy or inherited disorders in a minimally invasive manner may represent a major advancement for the future of embryo viability assessment. Recent studies have demonstrated that both blastocoele fluid and embryo culture medium contain genetic material, which can be isolated and subjected to downstream genetic analysis. The blastocoele fluid may represent an alternative source of nuclear DNA for aneuploidy testing, although the degree to which the isolated genetic material is solely representative of the developing embryo is currently unclear. In addition to nuclear DNA, mitochondrial DNA (mtDNA) can be detected in the embryo culture medium. Currently, the origin of this nuclear and mtDNA has not been fully evaluated and there are several potential sources of contamination that may contribute to the genetic material detected in the culture medium. There is however evidence that the mtDNA content of the culture medium is related to embryo fragmentation levels and its presence is predictive of blastulation, indicating that embryo development may influence the levels of genetic material detected. If the levels of genetic material are strongly related to aspects of embryo quality, then this may be a novel biomarker of embryo viability. If the genetic material does have an embryo origin, the mechanisms by which DNA may be released into the blastocoele fluid and embryo culture medium are unknown, although apoptosis may play a role. While the presence of this genetic material is an exciting discovery, the DNA in the blastocoele fluid and embryo culture medium appears to be of low yield and integrity, which makes it challenging to study. Further research aimed at assessing the methodologies used for both isolating and analysing this genetic material, as well as tracing its origin, are needed in order to evaluate its potential for clinical use. Should such methodologies prove to be routinely successful and the DNA recovered demonstrated to be embryonic in origin, then they may be used in a minimally invasive and less technical methodology for genetic analysis and embryo viability assessment than those currently available. PMID- 27270970 TI - Regulation of Airway Inflammation by G-protein Regulatory Motif Peptides of AGS3 protein. AB - Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and lung infections have critical consequences on mortality and morbidity in humans. The aims of the present study were to examine the mechanisms by which CXCL12 affects MUC1 transcription and airway inflammation, which depend on activator of G-protein signaling (AGS) 3 and to identify specific molecules that suppress CXCL12-induced airway inflammation by acting on G-protein-coupled receptors. Herein, AGS3 suppresses CXCL12-mediated upregulation of MUC1 and TNFalpha by regulating Galphai. We found that the G-protein regulatory (GPR) motif peptide in AGS3 binds to Galphai and downregulates MUC1 expression; in contrast, this motif upregulates TNFalpha expression. Mutated GPR Q34A peptide increased the expression of MUC1 and TGFbeta but decreased the expression of TNFalpha and IL-6. Moreover, CXCR4-induced dendritic extensions in 2D and 3D matrix cultures were inhibited by the GPR Q34A peptide compared with a wild-type GPR peptide. The GPR Q34A peptide also inhibited CXCL12-induced morphological changes and inflammatory cell infiltration in the mouse lung, and production of inflammatory cytokines in bronchoalveolar lavage (BAL) fluid and the lungs. Our data indicate that the GPR motif of AGS3 is critical for regulating MUC1/Muc1 expression and cytokine production in the inflammatory microenvironment. PMID- 27270972 TI - Pregnancy and birth outcomes following fresh or vitrified embryo transfer according to blastocyst morphology and expansion stage, and culturing strategy for delayed development. AB - STUDY QUESTION: How do live birth rates (LBRs), following fresh and vitrified/warmed embryo transfer, compare according to morphological grade, developmental stage and culturing strategy of human blastocysts in vitro? SUMMARY ANSWER: Equivalent LBRs were obtained after fresh embryo transfer and after vitrified/warmed embryo transfer of blastocysts of top or non-top quality, while vitrification after prolonged embryo culture of blastocysts with delayed development had a positive impact on LBR. WHAT IS KNOWN ALREADY: Blastocyst morphology correlates with clinical outcome; however, few data are available on vitrified/warmed embryo transfer using non-top quality blastocysts. The aim of this study was to determine clinical outcomes of non-top quality blastocysts and blastocysts with delayed development that underwent vitrified/warmed embryo transfer. STUDY DESIGN, SIZE, DURATION: This retrospective, single-centre study (conducted January 2009 to June 2013) compared 1010 fresh embryo transfer and 1270 vitrified/warmed embryo transfer of blastocysts originating from the same stimulation cycle. Furthermore, 636 fresh embryo transfers and 304 vitrified/warmed embryo transfer after delayed expansion or blastulation in the same period were also analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clinical outcomes after fresh and vitrified/warmed embryo transfer according to blastocyst morphology were compared in both groups. MAIN RESULTS AND THE ROLE OF CHANCE: Similar LBRs after fresh embryo transfer or after vitrified/warmed embryo transfer of top or non-top quality blastocysts were observed. A statistically significant improvement in clinical outcomes was obtained after vitrified/warmed embryo transfer of Day 5 embryos with delayed expansion or blastulation when applying prolonged culture. Our study suggests that vitrification of non-top quality blastocysts as well as delayed cavitating and blastulating Day 5 embryos should be considered in autologous IVF cycles. LIMITATIONS AND REASONS FOR CAUTION: Given that the present retrospective study used aseptic vitrification of blastocysts, the results, particularly the survival rates, may not be fully applicable to other vitrification protocols. The retrospective nature of the study has to be mentioned. WIDER IMPLICATIONS OF THE FINDINGS: Restriction of vitrification to top quality blastocysts may result in discarding potentially viable embryos. STUDY FUNDING AND COMPETING INTERESTS: This study was not externally funded. There are no conflicts of interest to declare. PMID- 27270974 TI - Molecular and mesoscale mechanism for hierarchical self-assembly of dipeptide and porphyrin light-harvesting system. AB - A multi-scale theoretical investigation of dipeptide-porphyrin co-assembly systems has been carried out to establish such understanding, where two different types of the dipeptides, dilysine (KK(3+)) and diphenylalanine (FF(+)) are compared on tuning the porphyrin organization. Density functional theory results reveal that the electrostatic attraction between different functional groups has significantly strengthened the hydrogen bonds between them, which are considered as the driving force of the self-assembly at the molecular level. All-atom molecular dynamics (MD) simulation further indicates that the formation of the core-shell nanorods is driven and stabilized by the hydrophobic interaction between dipeptides and negatively charged porphyrin (H2TPPS(2-)), where the packed porphyrins stay inside as the core of the nanorods and the hydrophilic groups (amino- and carboxyl-groups) as the shell. With stronger hydrophobicity, FF(+) is more likely to insert into the porphyrin aggregates and build crosslinks than KK(3+). Moreover, dissipative particle dynamics (DPD) simulation suggests equilibrium morphologies with different dipeptides, where KK(3+)-H2TPPS(2-) assembled in fiber bundles, whereas FF(+)-H2TPPS(2-) assembled as microspheres, corresponding to the different packing behavior in MD simulations. The consistency of these results at different scales is discussed. The method used in this work could be extended for studying similar issues in hierarchical self assembly of building blocks such biomaterials. PMID- 27270973 TI - Self-reported onset of puberty and subsequent semen quality and reproductive hormones in healthy young men. AB - STUDY QUESTION: Is there an association between pubertal onset and subsequent reproductive health in young men? SUMMARY ANSWER: Self-reported later onset of puberty was associated with reduced semen quality and altered serum levels of reproductive hormones among 1068 healthy, young Danish men. WHAT IS KNOWN ALREADY: The long-term effects of variations in the onset of male puberty on subsequent reproduction remain largely unstudied. STUDY DESIGN, SIZE, DURATION: In a cross-sectional study, young healthy Danish men were approached when they attended a compulsory medical examination to determine their fitness for military service from 2008 to 2012. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: A total of 1068 healthy, young Danish men (mean age 19 years) participated. They were asked to assess whether onset of penile and testicular growth, development of pubic hair and voice break occurred earlier, at the same time as or later than their peers. Their semen quality (semen volume, sperm concentration, total sperm count and percentages of motile and morphologically normal spermatozoa) and serum concentrations of sex hormones (LH, FSH, total testosterone, SHBG, inhibin B) and testicular size were determined. MAIN RESULTS AND THE ROLE OF CHANCE: The response rate was 29%. Of the 1068 men who then participated, 652 answered the questions about penile growth and pubic hair development and were therefore included in the analysis. Self-reported later onset of puberty was associated with a 25% reduction in sperm concentration (95% CI -41%; -4%), a 40% reduction in total sperm count (-55%; -21%), a 1.6% age point reduction in morphological normal spermatozoa (-2.9; -0.3) and a 1.6 ml reduction in testicular size (-2.4 and -0.8 ml), after adjustment for confounders. Self-reported later onset of puberty was also associated with a 9% (3%; 15%) reduction in free testosterone and a 16% (2%; 31%) increase in FSH, after adjustment for confounders. LIMITATIONS, REASON FOR CAUTION: Our study was cross-sectional and reverse causality cannot be ruled out. In addition, we cannot rule out the possibility that the men with late puberty onset had not yet fully matured although most were in Tanner stage 5. WIDER IMPLICATIONS OF THE FINDINGS: Approximately 15% of young Danish men have self-reported later onset of puberty than their peers. We found poorer testicular function in young men with a history of later pubertal development, suggesting that timing of pubertal onset may be a fundamental marker of male reproductive health. However, we cannot exclude the possibility that these men had not fully matured at the time of examination and therefore their semen quality may yet improve, which makes follow-up important. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (project number 2101-08-0058), Rigshospitalet (grants 961506336 and R42-A1326), European Union, DEER (grant agreement no 212844), the Danish Ministry of Health and the Danish Environmental Protection Agency and Kirsten and Freddy Johansens Foundation (grant 95-103-72087). There are no competing interests. PMID- 27270985 TI - Reply to letter to the editor "tDCS effect on cognitive performance in Parkinson's disease" by Biundo et al. PMID- 27270986 TI - Relevance of the test content of the Korean Nursing Licensing Examination to nursing job. AB - PURPOSE: This study aimed at identifying if there is a relevance of content of the Korean Nursing Licensing Examination (KNLE) revised in 2014 to nursing job. It will be able to provide the validity of revised content of the KNLE. METHODS: From October 13 to November 13, 2015, print version of 8 duties with 49-tasks, 155-job item questionnaires were distributed to 1,305 hospital nurses and 202 nursing faculties in Korea. Results were treated by descriptive statistics and comparison analysis. There were responses from 946 nurses or professors (72.5%). RESULTS: The relevance of test content of KNLE to nursing job was shown to be valid with over 3 points out of 4 point Likert scale in all items: from 3.23 at lowest to 3.64 at top. CONCLUSION: Above results showed that the revised version of KNLE in 2014 was valid to test the nursing students' knowledge for job performance. PMID- 27270987 TI - The job analysis of Korean nurses as a strategy to improve the Korean Nursing Licensing Examination. AB - PURPOSE: This study aimed at characterizing Korean nurses' occupational responsibilities to apply the results for improvement of the Korean Nursing Licensing Examination. METHODS: First, the contents of nursing job were defined based on a focus group interview of 15 nurses. Developing a Curriculum (DACOM) method was used to examine those results and produce the questionnaire by 13 experts. After that, the questionnaire survey to 5,065 hospital nurses was done. RESULTS: The occupational responsibilities of nurses were characterized as involving 8 duties, 49 tasks, and 303 task elements. Those 8 duties are nursing management and professional development, safety and infection control, the management of potential risk factors, basic nursing and caring, the maintenance of physiological integrity, medication and parenteral treatments, socio psychological integrity, and the maintenance and improvement of health. CONCLUSION: The content of Korean Nursing Licensing Examination should be improved based on 8 duties and 49 tasks of the occupational responsibilities of Korean nurses. PMID- 27270988 TI - Remodelling after an Infarct: Crosstalk between Life and Death. PMID- 27270989 TI - Diagnosis and Treatment of Dyssynergic Defecation. AB - Dyssynergic defecation is common and affects up to one half of patients with chronic constipation. This acquired behavioral problem is due to the inability to coordinate the abdominal and pelvic floor muscles to evacuate stools. A detailed history, prospective stool diaries, and a careful digital rectal examination will not only identify the nature of bowel dysfunction, but also raise the index of suspicion for this evacuation disorder. Anorectal physiology tests and balloon expulsion test are essential for a diagnosis. Newer techniques such as high resolution manometry and magnetic resonance defecography can provide mechanistic insights. Recently, randomized controlled trials have shown that biofeedback therapy is more effective than laxatives and other modalities, both in the short term and long term, without side effects. Also, symptom improvements correlated with changes in underlying pathophysiology. Biofeedback therapy has been recommended as the first-line of treatment for dyssynergic defecation. Here, we provide an overview of the burden of illness and pathophysiology of dyssynergic defecation, and how to diagnose and treat this condition with biofeedback therapy. PMID- 27270991 TI - Minimally Invasive Surgery. PMID- 27270992 TI - Cytotoxicity Effects and Apoptosis Induction by Bisbenzylisoquinoline Alkaloids from Triclisia subcordata. AB - Triclisia subcordata Oliv (Menispermeaceae) is a medicinal plant traditionally used for the treatment of various diseases in West Africa. The ethanol extract of T. subcordata and its fractions were screened for in vitro anti-ovarian cancer activities using the Sulforhodamine B assay. The crude alkaloids showed the strongest activity in cell growth assays on Ovcar-8 and A2780 cell lines (IC50 < 2.4 ug/mL). A bisbenzylisoquinoline alkaloid-cycleanine was isolated using HPLC and identified by mass spectrometry and nuclear magnetic resonance analyses. The IC50 values of cycleanine and tetrandrine (an alkaloid previously reported from this plant) ranged from 7 to 14 MUM on Ovcar-8, A2780, Ovcar-4, and Igrov-1 ovarian cancer cell lines. The IC50 of cycleanine on human normal ovarian surface epithelial cells was 35 +/- 1 MUM, hinting at modest selectivity toward cancer cells. Both cycleanine and tetrandrine caused apoptosis as shown by activation of caspases 3/7 and cleavage of poly(ADP-ribose) polymerase to form poly(ADP-ribose) polymerase-1 by using western blot analysis. Flow cytometry analyses showed that the percentages of apoptotic cells and cells in subG1 phase increased after exposure of cycleanine and tetrandrine to Ovcar-8 cells for 48 h compared with control. Cycleanine, like its isomer tetrandrine isolated from T. subcordata, could be a potential new anti-ovarian cancer agent acting through the apoptosis pathway. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27270990 TI - Inhibition of microtubule dynamics impedes repair of kidney ischemia/reperfusion injury and increases fibrosis. AB - The microtubule cytoskeleton is composed of alpha-tubulin and beta-tubulin heterodimers, and it serves to regulate the shape, motility, and division of a cell. Post-translational modifications including acetylation are closely associated with the functional aspects of the microtubule, involving in a number of pathological diseases. However, the role of microtubule acetylation in acute kidney injury (AKI) and progression of AKI to chronic kidney disease have yet to be understood. In this study, ischemia/reperfusion (I/R), a major cause of AKI, resulted in deacetylation of the microtubules with a decrease in alpha-tubulin acetyltransferase 1 (alpha-TAT1). Paclitaxel (taxol), an agent that stabilizes microtubules by tubulin acetylation, treatment during the recovery phase following I/R injury inhibited tubular cell proliferation, impaired renal functional recovery, and worsened fibrosis. Taxol induced alpha-tubulin acetylation and post-I/R cell cycle arrest. Taxol aggregated the microtubule in the cytoplasm, resulting in suppression of microtubule dynamics. Our studies have demonstrated for the first time that I/R induced deacetylation of the microtubules, and that inhibition of microtubule dynamics retarded repair of injured tubular epithelial cells leading to an acceleration of fibrosis. This suggests that microtubule dynamics plays an important role in the processes of repair and fibrosis after AKI. PMID- 27270993 TI - Neuropathic pain in patients with chronic leg ulcers. AB - BACKGROUND: Leg ulcers are a frequent and often painful disorder. This pain is not always correctly evaluated and relieved. OBJECTIVES: The aim of this prospective study is to assess the contribution of neuropathic pain in leg ulcers. METHODS: A visual analog scale and the DN4 questionnaire were fulfilled by 81 patients with leg ulcers. RESULTS: Of the patients with leg ulcers, 58% (n = 47) had a positive DN4 score. No predictive factor leading to neuropathic pain was found. The aetiology of the ulcers did not influence the DN4 score. CONCLUSIONS: This high prevalence of neuropathic pain in leg ulcers might be explained by an impairment of peripheral nerves due to ischaemia. This study also highlights the difficulty to relieve pain in chronic wounds; 16 patients had an analogous visual scale above 7. These results should encourage practitioners to regularly screen for neuropathic pain and to initiate appropriate treatment if necessary. PMID- 27270997 TI - Wettability modified nanoporous ceramic membrane for simultaneous residual heat and condensate recovery. AB - Recovery of both latent heat and condensate from boiler flue gas is significant for improving boiler efficiency and water conservation. The condensation experiments are carried out to investigate the simultaneous heat and mass transfer across the nanoporous ceramic membranes (NPCMs) which are treated to be hydrophilic and hydrophobic surfaces using the semicontinuous supercritical reactions. The effects of typical parameters including coolant flow rate, vapor/nitrogen gas mixture temperature, water vapor volume fraction and transmembrane pressure on heat and mass transfer performance are studied. The experimental results show that the hydrophilic NPCM exhibits higher performances of condensation heat transfer and condensate recovery. However, the hydrophobic modification results in remarkable degradation of heat and condensate recovery from the mixture. Molecular dynamics simulations are conducted to establish a hydrophilic/hydrophobic nanopore/water liquid system, and the infiltration characteristics of the single hydrophilic/hydrophobic nanopore is revealed. PMID- 27270998 TI - A SnOx-brookite TiO2 bilayer electron collector for hysteresis-less high efficiency plastic perovskite solar cells fabricated at low process temperature. AB - Thin plastic film-based CH3NH3PbI3-xClx perovskite solar cells were fabricated at low process temperature using a bilayer comprising an amorphous SnOx and mesoporous brookite TiO2 as electron collectors. Void-less high quality heterojunction structures achieve hysteresis-less photovoltaic performance with a power conversion efficiency as high as 13.4% and mechanical stability against cyclic bending. PMID- 27270999 TI - An evolutionary perspective of AMPK-TOR signaling in the three domains of life. AB - AMPK and TOR protein kinases are the major control points of energy signaling in eukaryotic cells and organisms. They form the core of a complex regulatory network to co-ordinate metabolic activities in the cytosol with those in the mitochondria and plastids. Despite its relevance, it is still unclear when and how this regulatory pathway was formed during evolution, and to what extent its representations in the major eukaryotic lineages resemble each other. Here we have traced 153 essential proteins forming the human AMPK-TOR pathways across 412 species representing all three domains of life-prokaryotes (bacteria, archaea) and eukaryotes-and reconstructed their evolutionary history. The resulting phylogenetic profiles indicate the presence of primordial core pathways including seven proto-kinases in the last eukaryotic common ancestor. The evolutionary origins of the oldest components of the AMPK pathway, however, extend into the pre-eukaryotic era, and descendants of these ancient proteins can still be found in contemporary prokaryotes. The TOR complex in turn appears as a eukaryotic invention, possibly to aid in retrograde signaling between the mitochondria and the remainder of the cell. Within the eukaryotes, AMPK/TOR showed both a highly conserved core structure and a considerable plasticity. Most notably, KING1, a protein originally assigned as the gamma subunit of AMPK in plants, is more closely related to the yeast SDS23 gene family than to the gamma subunits in animals or fungi. This suggests its functional difference from a canonical AMPK gamma subunit. PMID- 27271001 TI - [Telemedicine-assisted treatment of a 76-year-old man with heart failure]. AB - The case of a patient with dilated cardiomyopathy and severely impaired left ventricular function is reported. With existing complete left bundle branch block and the patient being on optimal medical therapy, a cardiac resynchronization device with an integrated defibrillator was implanted and the patient was included in our telemonitoring program. During monitoring, an increase in ventricular premature beats with a decrease in biventricular pacing percentage was noticed. Consequently, radiofrequency ablation of the ventricular premature beats which originated in the left ventricle was performed. After ablation we could demonstrate a significant increase in biventricular pacing percentage. This case shows the importance of telemedicine and the complexity in the rhythmological treatment of heart failure patients. PMID- 27271000 TI - A 2-Cys peroxiredoxin in response to oxidative stress in the pine wood nematode, Bursaphelenchus xylophilus. AB - The pine wood nematode, Bursaphelenchus xylophilus, is the causal agent of pine wilt disease that has devastated pine forests in Asia. Parasitic nematodes are known to have evolved antioxidant stress responses that defend against host plant defenses. In this study, the infestation of whitebark pine, Pinus bungean, with B. xylophilus led to a significant increase in plant hydrogen peroxide (H2O2) and salicylic acid levels. Correspondingly, the expression of an antioxidative enzyme, 2-Cysteine peroxiredoxin (BxPrx), was elevated in B. xylophilus following the H2O2 treatments. Recombinant BxPrx, a thermal stabile and pH tolerant enzyme, exhibited high level of antioxidant activity against H2O2, suggesting that it is capable of protecting cells from free radical attacks. Immunohistochemical localization study showed that BxPrx was broadly expressed across different tissues and could be secreted outside the nematode. Finally, the number of BxPrx homologs in both dauer-like and fungi-feeding B. xylophilus were comparable based on bioinformatics analysis of existing EST libraries, indicating a potential role of BxPrx in both propagative and dispersal nematodes. These combined results suggest that BxPrx is a key genetic factor facilitating the infestation and distribution of B. xylophilus within pine hosts, and consequently the spread of pine wilt disease. PMID- 27271002 TI - Theory of mind and Verstehen (understanding) methodology. AB - Theory of mind is a prominent, but highly controversial, field in psychology, psychiatry, and philosophy of mind. Simulation theory, theory-theory and other views have been presented in recent decades, none of which are monolithic. In this article, various views on theory of mind are reviewed, and methodological problems within each view are investigated. The relationship between simulation theory and Verstehen (understanding) methodology in traditional human sciences is an intriguing issue, although the latter is not a direct ancestor of the former. From that perspective, lessons for current clinical psychiatry are drawn. PMID- 27271003 TI - Development of the Modified Four Square Step Test and its reliability and validity in people with stroke. AB - Adults with stroke have difficulty avoiding obstacles when walking, especially when a time constraint is imposed. The Four Square Step Test (FSST) evaluates dynamic balance by requiring individuals to step over canes in multiple directions while being timed, but many people with stroke are unable to complete it. The purposes of this study were to (1) modify the FSST by replacing the canes with tape so that more persons with stroke could successfully complete the test and (2) examine the reliability and validity of the modified version. Fifty-five subjects completed the Modified FSST (mFSST) by stepping over tape in all four directions while being timed. The mFSST resulted in significantly greater numbers of subjects completing the test than the FSST (39/55 [71%] and 33/55 [60%], respectively) (p < 0.04). The test-retest, intrarater, and interrater reliability of the mFSST were excellent (intraclass correlation coefficient ranges: 0.81 0.99). Construct and concurrent validity of the mFSST were also established. The minimal detectable change was 6.73 s. The mFSST, an ideal measure of dynamic balance, can identify progress in people with stroke in varied settings and can be completed by a wide range of people with stroke in approximately 5 min with the use of minimal equipment (tape, stop watch). PMID- 27271004 TI - Correction: Excitation of vibrational soft modes in disordered systems using active oscillation. AB - Correction for 'Excitation of vibrational soft modes in disordered systems using active oscillation' by Elsen Tjhung et al., Soft Matter, 2016, DOI: . PMID- 27271005 TI - Peptide protected gold clusters: chemical synthesis and biomedical applications. AB - Bridging the gap between atoms and nanoparticles, noble metal clusters with atomic precision continue to attract considerable attention due to their important applications in catalysis, energy transformation, biosensing and biomedicine. Greatly different to common chemical synthesis, a one-step biomimetic synthesis of peptide-conjugated metal clusters has been developed to meet the demand of emerging bioapplications. Under mild conditions, multifunctional peptides containing metal capturing, reactive and targeting groups are rationally designed and elaborately synthesized to fabricate atomically precise peptide protected metal clusters. Among them, peptide protected Au Cs (peptide-Au Cs) possess a great deal of exceptional advantages such as nanometer dimensions, high photostability, good biocompatibility, accurate chemical formula and specific protein targeting capacity. In this review article, we focus on the recent advances in potential theranostic fields by introducing the rising progress of peptide-Au Cs for biological imaging, biological analysis and therapeutic applications. The interactions between Au Cs and biological systems as well as potential mechanisms are also our concerned theme. We expect that the rapidly growing interest in Au Cs-based theranostic applications will attract broader concerns across various disciplines. PMID- 27271007 TI - Efficient treatment allocation in 2 * 2 cluster randomized trials, when costs and variances are heterogeneous. AB - Typically, clusters and individuals in cluster randomized trials are allocated across treatment conditions in a balanced fashion. This is optimal under homogeneous costs and outcome variances. However, both the costs and the variances may be heterogeneous. Then, an unbalanced allocation is more efficient but impractical as the outcome variance is unknown in the design stage of a study. A practical alternative to the balanced design could be a design optimal for known and possibly heterogeneous costs and homogeneous variances. However, when costs and variances are heterogeneous, both designs suffer from loss of efficiency, compared with the optimal design. Focusing on cluster randomized trials with a 2 * 2 design, the relative efficiency of the balanced design and of the design optimal for heterogeneous costs and homogeneous variances is evaluated, relative to the optimal design. We consider two heterogeneous scenarios (two treatment arms with small, and two with large, costs or variances, or one small, two intermediate, and one large costs or variances) at each design level (cluster, individual, and both). Within these scenarios, we compute the relative efficiency of the two designs as a function of the extents of heterogeneity of the costs and variances, and the congruence (the cheapest treatment has the smallest variance) and incongruence (the cheapest treatment has the largest variance) between costs and variances. We find that the design optimal for heterogeneous costs and homogeneous variances is generally more efficient than the balanced design and we illustrate this theory on a trial that examines methods to reduce radiological referrals from general practices. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271006 TI - Thermodynamics, Disequilibrium, Evolution: Far-From-Equilibrium Geological and Chemical Considerations for Origin-Of-Life Research. PMID- 27271008 TI - It is complicated: gender and sexual orientation identity in LGBTQ youth. AB - AIMS AND OBJECTIVES: To explore the variations of sexual orientation and gender identity as well as the intersections of those identities in a sample of lesbian, gay, bisexual, transgender, queer, and questioning youth. BACKGROUND: Identity development is a key task of adolescence. Among the multiple identities that young people navigate are sexual orientation and gender identity. Challenges with solidifying and integrating aspects of one's identity can contribute to poor physical and mental health outcomes. DESIGN: Cross-sectional descriptive survey. METHODS: A convenience sample was recruited via collaborations with community organisations and Internet groups who provide information and services for LGBTQ youth under the age of 25. RESULTS: Of the 175 respondents, one-third of the sample reported a gender identity that was not congruent with their sex assigned at birth. Those assigned female sex at birth reported noncongruent gender identities as well as fluid and nonbinary identities such as genderqueer and agender more frequently that respondents assigned male at birth. Individuals with noncongruent gender identities were more likely to identify with a sexual orientation other than lesbian, gay or bisexual than individuals with gender identities congruent with their sex assigned at birth. CONCLUSIONS: Adolescent sexual orientation and gender identity are complex and nuanced. Nurse scientists and clinical nurses can contribute to understanding of these identities, their meaning to the young person and the unique health implications by regularly inquiring about sexual orientation and gender identity in their practice. RELEVANCE TO CLINICAL PRACTICE: Nurses in clinical practice need to be aware of the sometimes complicated nature of adolescent identity and its related terminology so that they can ask relevant questions and provide culturally safe care. PMID- 27271009 TI - M2-polarized macrophages contribute to neovasculogenesis, leading to relapse of oral cancer following radiation. AB - Despite the fact that radiation is one of the standard therapies in the treatment of patients with oral cancer, tumours can recur even in the early stages of the disease, negatively impacting prognosis and quality of life. We previously found that CD11b(+) bone marrow-derived cells (BMDCs) were recruited into human glioblastoma multiforme (GBM), leading to re-organization of the vasculature and tumour regrowth. However, it is not yet known how these cells contribute to tumour vascularization. In the present study, we investigated the role of infiltrating CD11b(+) myeloid cells in the vascularization and recurrence of oral squamous cell carcinoma (OSCC). In a xenograft mouse model, local irradiation caused vascular damage and hypoxia in the tumour and increased infiltration of CD11b(+) myeloid cells. These infiltrating cells showed characteristics of M2 macrophages (M2Mphis) and are associated with the promotion of vascularization. M2Mphis promoted tumour progression in recurrence after irradiation compared to non-irradiated tumours. In addition, we found that CD11b(+) myeloid cells, as well as CD206(+) M2Mphis, are increased during recurrence after radiotherapy in human OSCC specimens. Our findings may lead to the development of potential clinical biomarkers or treatment targets in irradiated OSCC patients. PMID- 27271010 TI - Impact of South Carolina's Medicaid fluoride varnish reimbursement policy on children's receipt of fluoride varnish in medical and dental settings. AB - OBJECTIVE: We estimated the effect of South Carolina's (SC) Medicaid fluoride varnish (FV) reimbursement policy on children's receipt of fluoride varnish in medical (MFV) and dental (DFV) settings. METHODS: We obtained data from SC Medicaid enrollment and claims files for children <= 47 months of age across State Fiscal Years (SFY) 2008-2013 and created a panel dataset of 52,841 children representing 126,464 child-years of observation. Pooled multivariate logistic regression models were estimated to identify factors associated with a higher likelihood of a child receiving one or more MFV or DFV treatments. RESULTS: The FV rates per child-year were 1 percent for physicians and 23 percent for dentists, respectively. The child-year rate for receipt of FV from both a physician and a dentist was less than one-third of one percent. CONCLUSIONS: A policy designed to increase access to FV treatments from physicians and dentists for children up to forty-seven months of age was not successful for physicians; however, the positive findings for dentists were promising. PMID- 27271012 TI - Thermoset Shape-Memory Polyurethane with Intrinsic Plasticity Enabled by Transcarbamoylation. AB - Thermoset polymers are known for their superior thermomechanical properties, but the chemical crosslinking typically leads to intractability. This is reflected in the great differences between thermoset and thermoplastic shape-memory polymers; the former exhibit a robust shape memory but are not capable of redefining the permanent shape. Contrary to current knowledge, we reveal here that a classical thermoset shape-memory polyurethane is readily capable of permanent reshaping (plasticity) after a topological network rearrangement that is induced by transcarbamoylation. By employing the Jianzhi technique (also known as kirigami), unexpected shape-shifting versatility was observed for this otherwise classical material. As the essential carbamate moiety in polyurethanes is one of the most common polymer building units, we anticipate that our finding will have significant benefits beyond shape shifting. PMID- 27271011 TI - Inhibition of inflammatory reactions in 2,4-Dinitrochlorobenzene induced Nc/Nga atopic dermatitis mice by non-thermal plasma. AB - Non-thermal plasma (NTP) has recently been introduced and reported as a novel tool with a range of medicinal and biological roles. Although many studies using NTP have been performed, none has investigated the direct relationship between NTP and immune responses yet. Especially, the effects of NTP on atopic dermatitis (AD) were not been explored. Here, NTP was tested whether it controls immune reactions of AD. NTP treatment was administered to pro-inflammatory cytokine stimulated keratinocytes and DNCB (2,4-Dinitrochlorobenzene)-induced atopic dermatitis mice, then the immune reactions of cells and skin tissues were monitored. Cells treated with NTP showed decreased expression levels of CCL11, CCL13, and CCL17 along with down-regulation of NF-kappaB activity. Repeated administration of NTP to AD-induced mice reduced the numbers of mast cells and eosinophils, IgE, CCL17, IFNgamma levels, and inhibited NF-kappaB activity in the skin lesion. Furthermore, combined treatment with NTP and 1% hydrocortisone cream significantly decreased the immune responses of AD than that with either of these two treatments individually. Overall, this study revealed that NTP significantly inhibits several immune reactions of AD by regulating NF-kappaB activity. Therefore, NTP could be useful to suppress the exaggerated immune reactions in severe skin inflammatory diseases such as AD. PMID- 27271013 TI - Novel TetR family transcriptional factor regulates expression of multiple transport-related genes and affects rifampicin resistance in Mycobacterium smegmatis. AB - Transport-related genes significantly affect bacterial antibiotic resistance. However, the effects of these genes and their regulation of bacterial drug resistance in several mycobacterial species, including the fast-growing Mycobacterium smegmatis, the pathogen M. tuberculosis and M. avium have not been clearly characterized. We identified Ms4022 (MSMEG_4022) as a novel TetR family regulator that activates the expression of seven transport-related genes and affects drug resistance in M. smegmatis. Overexpression of Ms4022 inhibited M. smegmatis growth and enhanced mycobacterial resistance to the anti-tuberculosis drug rifampicin (RIF). By contrast, the Ms4022-deleted mycobacterial strain has shown sensitive to RIF. Ms4022 recognized three 19 bp non-palindromic motifs containing a 9 bp conserved region at their 5' end and it directly regulated seven transport-related genes, which affects mycobacterial resistance to RIF. Overexpression of three of seven transport-related genes (Ms1448, Ms1613, and Ms5278) inhibited the growth of M. smegmatis. This study improves our understanding of the function of mycobacterial transport-related genes and their regulation of bacterial drug resistance. PMID- 27271016 TI - US132 Cyclodextrin Glucanotransferase Engineering by Random Mutagenesis for an Anti-Staling Purpose. AB - The use of the cyclodextrin glucanotransferase (CGTase) of the US132 strain, which is an effective anti-staling agent, has been hampered by its high cyclization activity. Since that random mutagenesis using error-prone PCR is nowadays a method of choice for enzymes engineering, we have optimized this method by adjusting manganese concentration in order to obtain a high percentage of active CGTase mutants. Therefore, the amplification of the gene encoding the US132 CGTase was performed using a MnCl2 concentration ranging between 0 and 0.5 mM. The finding showed that a manganese concentration of 0.04 mM allowed for 90 % of active mutants. A simple method to rapidly screen the obtained mutants was also developed. After the examination of a small library (of less than 1000 clones), the active mutant named MJ13 was selected for a significant decrease in the cyclization activity, thereby showing a remarkable change in the enzyme specificity towards starch dextrinizing. Sequence analysis showed that MJ13 is a triple mutant with two mutations in the catalytic domain (K47E and S382P) and one substitution in the starch binding domain (N655S). PMID- 27271017 TI - A Single-Cell-Type Real-Time PCR Method Based on a Modified Patch-Pipette Cell Harvesting System. AB - Real-time PCR is a powerful tool for quantifying nucleic acid expression. Real time PCR is conventionally performed at the tissue level to guarantee an abundance of nucleic acid for detection. The precision and reliability of this method, however, is limited by usually being composed of a mixture of different cell types. Single-cell PCR, in contrast, eliminates the purity problem of the cell source. However, use of this method is usually impeded by difficulties in cell harvesting and stringent requirements for processing of very small quantities of nucleic acids. In this study, we combined the advantages of the high purity of selected cells in single-cell PCR with the greater nucleic acid quantities and thus greater ease of tissue-level PCR. The key aspect of our method is to use a modified patch-clamp pipette to harvest several selected cells of the same type. This method is therefore especially useful for cells that can be morphologically or histologically identified such as primary sensory neurons, striated muscle fibers and cells labeled with fluorescent makers. PMID- 27271018 TI - Biopsychosocial problem-related distress in cancer: examining the role of sex and age. AB - BACKGROUND: The current study explores how sex and age relate to biopsychosocial distress by applying a large-scale analysis among individuals diagnosed with a variety of cancers. METHODS: A retrospective study was conducted involving 6462 patients treated for cancer at a National Cancer Institute-designated comprehensive cancer center between 2009 and 2014. Patients were asked to complete the biopsychosocial problem-related distress touchscreen instrument prior to starting treatment as part of their routine clinical care. RESULTS: There was a significant interaction of age and sex on the total number of problems rated as high distress and the total number of problems that prompted a request to talk with a member of the team. Male patients between 18 and 39 reported significantly more problems as high distress than female patients in the same age group (mean = 5.34 and mean = 4.92, respectively; p = 0.005). A similar trend was found where male patients between 18-39 and 40-64 requested to talk with a member of the team significantly more often than female patients in these same age groups (mean = 3.25 and mean = 3.22 vs. mean = 2.70 and mean = 3.07, respectively; p = 0.016). CONCLUSIONS: The results of the current study serve to refute generalizations regarding age or gender demographics and support preferences and thus reinforce the need to offer services in the context of cancer in flexible and varied ways. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271020 TI - Access to Silylated Pyrazole Derivatives by Palladium-Catalyzed C-H Activation of a TMS group. AB - A simple and efficient approach to new silylated heterocycles of potential interest in medicinal chemistry is presented. A set of bromophenyl trimethylsilyl pyrazole intermediates can be transformed by direct organometallic routes into two families of regioisomeric iodoaryl substrates; using either arylzinc or aryllithium chemistry, the TMS group remains on the pyrazole ring or translocates to the aryl moiety. These two families can then be efficiently transformed into benzo silino pyrazoles thanks to a single-step cyclization relying on the Pd catalyzed activation of a non-activated C(sp(3) )-H bond alpha to a silicon atom. The experimental conditions used, which are fully compatible with the pyrazole ring, suggest that this reaction evolves through a concerted metalation deprotonation (CMD) mechanism. PMID- 27271019 TI - Assisted care as a baseline patient risk characteristic affecting the outcome of transcatheter aortic valve insertion. AB - BACKGROUND: Objective measures of frailty have not been well defined as risk factors for a poor outcome after transcatheter aortic valve insertion. We hypothesized that assisted care as a baseline patient characteristic was a simple objective measure of frailty. We reviewed our experience to assess for an association between assisted care and outcome of operation. METHODS: We retrospectively reviewed the records of 597 patients operated with transcatheter aortic valve insertion from November 2008 through July 2015. The study cohort included patients with a dichotomous baseline characteristic of receiving assisted care (AC group, n = 60, 10.1%) or not receiving assisted care (NC group, n = 537, 89.9%). The endpoints of the study were operative stroke/death and 1 year survival. RESULTS: The age of the patients was 80.6 +/- 9.0 years, male sex was present in 349 (58.5%), and STS predicted risk of mortality was 9.2 +/- 6.2%. Alternate access was used in 26 (43.3%) patients in the AC care group and in 220 (41.0%) in the NC group (P = 0.724). Operative stroke/death occurred in 4 (6.7%) patients in the AC group and in 25 (4.7%) in the NC group (P = 0.492). Mortality at 1 year in the AC group was 14.8 +/- 5.2% and in the NC group was 12.9 +/- 1.7%; (P = 0. 250). CONCLUSIONS: Assisted care as a baseline patient characteristic does not result in increased operative stroke/death or 1-year mortality in patients following transcatheter aortic valve insertion. Assisted care should not by itself preclude operation. (c) 2016 Wiley Periodicals, Inc. PMID- 27271021 TI - Job satisfaction and burnout among paediatric nurses. AB - PURPOSE: This study aims to determine factors of job satisfaction and burnout levels of paediatric nurses. METHODS: A total of 165 nurses working in paediatric clinics completed the Minnesota job satisfaction scale and the Maslach burnout scale. FINDINGS: Average scores of the emotional exhaustion and depersonalisation score were low, while personal accomplishment scores were high. A high level of job satisfaction, being married, increased age and a decreased number of assigned patients were significantly associated with a low level of burnout. CONCLUSIONS: Paediatric nurses experience burnout at significant levels. The most important variable that affected job satisfaction was income. IMPLICATIONS FOR NURSING PRACTICE: The results of the study could guide development of strategies that might prevent or alleviate burnout of paediatric nurses. PMID- 27271022 TI - Spectrum of genomic alterations in FGFR3: current appraisal of the potential role of FGFR3 in advanced urothelial carcinoma. AB - Molecular analysis has identified subsets of urothelial carcinoma (UC) expressing distinct genetic signatures. Genomic alterations in the oncogenic fibroblast growth factor receptor 3 (FGFR3) pathway are among the most well described in UC and have led to extensive and ongoing investigation of FGFR3-targeted therapies in this disease, although no new drugs have yet been approved. Given the unmet need for effective treatments in advanced and metastatic UC, a better understanding of the known molecular alterations of FGFR3 and of the previous and ongoing clinical investigations of this promising target in UC deserves attention. The objective of the present review is to describe the landscape of alterations and biology of FGFR3 in UC, comprehensively summarize the current state of UC clinical trials of FGFR3 inhibitors, and discuss future therapeutic applications. Using the Pubmed and Clinicaltrials.gov databases, articles describing the spectrum and biological activity of FGFR3 genomic alterations and trials of FGFR3 inhibitors in UC were identified. Search terms included 'FGFR3 genomic alterations' and 'urothelial cancer' or 'bladder cancer'. Genomic alterations, including translocations and activating mutations, are increasingly described in advanced and metastatic UC. The majority of clinical trials have been performed in unselected populations; however, recent studies have reported encouraging preliminary data. We argue that routine use of molecular genomic tumour analysis in UC may inform selection of patients for appropriate trials and we further investigate the potential of FGFR3 as a meaningful clinical target for this difficult disease. PMID- 27271025 TI - Responsive Fluorescent PNA Analogue as a Tool for Detecting G-quadruplex Motifs of Oncogenes and Activity of Toxic Ribosome-Inactivating Proteins. AB - Fluorescent oligomers that are resistant to enzymatic degradation and report their binding to target oligonucleotides (ONs) by changes in fluorescence properties are highly useful in developing nucleic-acid-based diagnostic tools and therapeutic strategies. Here, we describe the synthesis and photophysical characterization of fluorescent peptide nucleic acid (PNA) building blocks made of microenvironment-sensitive 5-(benzofuran-2-yl)- and 5-(benzothiophen-2-yl) uracil cores. The emissive monomers, when incorporated into PNA oligomers and hybridized to complementary ONs, are minimally perturbing and are highly sensitive to their neighboring base environment. In particular, benzothiophene modified PNA reports the hybridization process with significant enhancement in fluorescence intensity, even when placed in the vicinity of guanine residues, which often quench fluorescence. This feature was used in the turn-on detection of G-quadruplex-forming promoter DNA sequences of human proto-oncogenes (c-myc and c-kit). Furthermore, the ability of benzothiophene-modified PNA oligomer to report the presence of an abasic site in RNA enabled us to develop a simple fluorescence hybridization assay to detect and estimate the depurination activity of ribosome-inactivating protein toxins. Our results demonstrate that this approach with responsive PNA probes will provide new opportunities to develop robust tools to study nucleic acids. PMID- 27271024 TI - Effectiveness of very early workplace interventions to reduce sickness absence: a systematic review of the literature and meta-analysis. AB - OBJECTIVE: The aim of this review was to investigate the effectiveness of workplace return-to-work (RTW) interventions delivered at very early stages (<15 days) of sickness absence (SA). METHODS: A systematic literature search was conducted in PubMed, Health Management Information Consortium (HMIC), Cochrane library database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsychInfo and Embase. Using pre-established criteria, independent pairs of researchers carried out the study selection, quality appraisal and data extraction. Workplace interventions before day 15 of SA, were included. Primary outcome measures included rates of and time until RTW, productivity loss, and recurrences of SA. RESULTS: We found limited available evidence on the benefits of "very early" workplace interventions in terms of RTW after a SA episode compared to usual care. Only three randomized controlled trials classed as high or intermediate quality were identified. Early part-time sick leave together with appropriate job modifications led to a reduction in the duration and recurrence of SA. There is evidence of benefit of intervening during the first two weeks of SA for musculoskeletal disorders. CONCLUSION: Our review has identified a lack of evidence from the literature at this time point to support "very early" intervention compared to usual care. The methodological design of the studies, notably the extent and timing of usual care provided and variable compliance/crossover between groups could however explain the lack of demonstrated benefit. Consensus is required on the definition of "early" and "very early" interventions, and further research is recommended to improve understanding of the factors influencing when and how best to intervene for maximum gain. PMID- 27271026 TI - Factors Associated with Pregnancy among Incarcerated African American Adolescent Girls. AB - The purpose of this study was to examine the social and behavioral factors associated with pregnancy history among a sample of African American adolescent girls recruited from a short-term juvenile detention center in order to better understand the needs of this vulnerable population. Data were collected from a sample of 188 detained African American, 13-17-year-old girls in Atlanta, Georgia, who participated in a larger HIV prevention study. An audio computer assisted self-interviewing survey was completed by participants to obtain information on socioecological factors to include individual, parental/familial, sexual risk, psychosocial, and substance use factors. Among the 188 participants, 25.5 % reported a history of pregnancy. A multivariable logistic regression model showed that girls with a history of pregnancy were more likely to live in a household receiving government aid, use hormonal contraceptives at last sex, participate in sex trading, have casual sex partners, have condomless sex in the past 90 days, and have a history of physical abuse. Girls with no history of pregnancy were more likely to have been incarcerated at least twice and to have previously used alcohol. Detention-based interventions and pregnancy prevention programs for this vulnerable population may benefit by addressing factors related to sexual behavior and development, substance use, individual background, and psychosocial health. PMID- 27271027 TI - Informal caregiving in head and neck cancer: caregiving activities and psychological well-being. AB - The purpose of this study was to quantify the general cancer support activities that long-term carers of head and neck cancer (HNC) survivors engage in; and the relationships between these care activities and psychological well-being. Respondents answered a survey detailing their caring activities, the amount of time that they spent on those activities and how comfortable they felt engaging in them. Psychological well-being was assessed by the Depression Anxiety Stress Scales-21. A total of 197 carers took part in the study. The majority (76%) were women, mean age 57.4. Mean time since diagnosis was 6.2 years. In the past month, 45% of carers did not spend any extra time per week helping their relative/friend with general caring activities such as cleaning the house; 31% spent 1-19 hr/week and 23% spent 20 or more hours/week doing so. Most carers were comfortable assisting their relative/friend, though more carers felt uncomfortable assisting with HNC-specific support tasks (31% uncomfortable helping with medication) compared with general support tasks (7% uncomfortable helping with appointments). Feeling uncomfortable with head and neck-specific care tasks was a significant predictor of experiencing depression and anxiety. PMID- 27271028 TI - Interaction of Target Oxygen Saturation, Bronchopulmonary Dysplasia, and Pulmonary Hypertension in Small for Gestational Age Preterm Neonates-Reply. PMID- 27271030 TI - Synthesis of beta,beta-diaryl propiophenones via palladium-catalyzed domino arylboronation, elimination and enone hydroarylation of enaminones. AB - The syntheses of beta,beta-diaryl aryl propiophenones have been realized via palladium-catalyzed domino reactions of dimethyl amino functionalized enaminones and aryl boronic acids. This is the first example of transition metal-catalyzed enaminone C-N bond conversion for the generation of a new C-C(aryl) structure. PMID- 27271031 TI - Impact of a new sampling buffer on faecal haemoglobin stability in a colorectal cancer screening programme by the faecal immunochemical test. AB - Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25 degrees C, range 22-28 degrees C) and up to 60% at outside temperature (29 degrees C, range 16-39 degrees C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 ug Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting. PMID- 27271032 TI - The Evolution of Recommended Naloxone Dosing for Opioid Overdose by Medical Specialty. AB - INTRODUCTION: Opioid abuse and opioid overdose deaths have increased significantly over the past decade. Naloxone is a potentially life-saving medication that can reverse opioid-induced respiratory depression, though precipitated opioid withdrawal can pose acute risks to the patient and medical personnel. The optimal naloxone dose is unclear and few studies address this question. METHODS: A convenience sample of commonly available references were queried for the recommended IV naloxone dose. When dosing recommendations were different for opioid-tolerant patients these were also recorded. RESULTS: Twenty five references were located. 48% recommended a starting dose <= 0.05 mg while 36% recommend a dose ten-fold higher. More than half of medical toxicology and general medical sources recommended a low-dose strategy with a starting dose lower than 0.05 mg IV. CONCLUSION: There are variations in the recommended doses for naloxone with ranges spanning an order of magnitude. Further exploration is needed to determine the dose that balances reversal of respiratory depression with mitigation of withdrawal. PMID- 27271034 TI - Correction: Ret and Etv4 Promote Directed Movements of Progenitor Cells during Renal Branching Morphogenesis. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002382.]. PMID- 27271033 TI - Prolonged respiratory disorder predicts adverse prognosis in infants with end stage kidney disease. AB - BACKGROUND: Among comorbidities, pulmonary hypoplasia (PH) is known as a significant risk factor for mortality in infants with end-stage kidney disease (ESKD). However, the final outcomes of infants with both ESKD and PH are still not well defined, as the diagnosis modality, and definition of PH severity remain ambiguous. METHODS: Children initiating peritoneal dialysis during infancy from 1990 to 2015 were followed until death, date of last contact, or the end of 2015. We examined the long-term outcome of children with congenital pulmonary disorders by studying infants with prolonged respiratory disorders of greater than 28 days duration after birth and evaluated risk factors for mortality. RESULTS: Forty-six children were followed (median follow-up, 9.23 years), and classified as children without (n = 38; Group A) or with (n = 8; Group B) a prolonged respiratory disorder. Overall actuarial 5 year survival rate in this cohort was 79.5 %. The survival curve in Group B showed a significant decline compared with Group A. Prolonged respiratory disorder was significantly associated with mortality by multivariate analysis (hazard ratio, 8.32). CONCLUSIONS: Infants who initiate peritoneal dialysis complicated by prolonged respiratory disorders have increased adverse risk factors for mortality; therefore, withholding aggressive treatment should be considered. PMID- 27271035 TI - D1- and D2-like dopamine receptors within the nucleus accumbens contribute to stress-induced analgesia in formalin-related pain behaviours in rats. AB - BACKGROUND: Stressful experiences can produce analgesia, termed stress-induced analgesia (SIA). Meanwhile, it has been widely established that the mesolimbic dopamine pathway and nucleus accumbens (NAc) have a profound role in pain modulation. In this study, we examined the role of accumbal dopamine receptors in antinociception caused by forced swim stress (FSS) in order to understand more about the function of these receptors within the NAc in FSS-induced analgesia. METHOD: Stereotaxic surgery was unilaterally performed on adult male Wistar rats weighing 230-250 g (some on the left and some on the right side of the midline). Two supergroups were microinjected into the NAc with a D1-like dopamine receptor antagonist, SCH-23390, at doses of 0.25, 1 and 4 MUg/0.5 MUl saline per rat or Sulpiride as a D2-like dopamine receptor antagonist at the same doses [0.25, 1 and 4 MUg/0.5 MUl dimethyl sulfoxide (DMSO) per rat]; while their controls just received intra-accumbal saline or DMSO at 0.5 MUl, respectively. The formalin test was performed after rats were subjected to FSS (6 min, 25 +/- 1 degrees C) to assess pain-related behaviours. RESULTS: The results demonstrated that intra accumbal infusions of SCH-23390 and Sulpiride dose-dependently reduced FSS induced antinociception in both phases of the formalin test. However, the percentage decrease in area under the curve (AUC) values calculated for treatment groups compared to formalin-control group was more significant in the late phase than the early phase. CONCLUSION: Our findings suggest that D1- and D2-like dopamine receptors in the NAc are involved in stress-induced antinociceptive behaviours in the formalin test as an animal model of persistent inflammatory pain. WHAT DOES THIS STUDY ADD: Forced swim stress (FSS) induces the antinociception in both phases of formalin test. Blockade of accumbal dopamine receptors attenuate the antinociception induced by FSS. Stress-induced analgesia is dose-dependently reduced by dopamine receptor antagonists in both phases, although it is more prominent during the late phase. PMID- 27271036 TI - Epigenetic Dysregulation Observed in Monosomy Blastocysts Further Compromises Developmental Potential. AB - Epigenetic mechanisms such as DNA methylation regulate genomic imprinting and account for the distinct non-equivalence of the parental genomes in the embryo. Chromosomal aneuploidy, a major cause of infertility, distorts this highly regulated disparity by the presence or absence of chromosomes. The implantation potential of monosomy embryos is negligible compared to their trisomy counterparts, yet the cause for this is unknown. This study investigated the impact of chromosomal aneuploidy on strict epigenetically regulated domains, specifically imprinting control regions present on aneuploid chromosomes. Donated cryopreserved human IVF blastocysts of transferable quality, including trisomy 15, trisomy 11, monosomy 15, monosomy 11, and donor oocyte control blastocysts were examined individually for DNA methylation profiles by bisulfite mutagenesis and sequencing analysis of two maternally methylated imprinting control regions (ICRs), SNRPN (15q11.2) and KCNQ1OT1 (11p15.5), and one paternally methylated imprinting control region, H19 (11p15.5). Imprinted genes within the regions were also evaluated for transcript abundance by RT-qPCR. Overall, statistically significant hypermethylated and hypomethylated ICRs were found in both the trisomy and monosomy blastocysts compared to controls, restricted only to the chromosome affected by the aneuploidy. Increased expression was observed for maternally-expressed imprinted genes in trisomy blastocysts, while a decreased expression was observed for both maternally- and paternally-expressed imprinted genes in monosomy blastocysts. This epigenetic dysregulation and altered monoallelic expression observed at imprinting control regions in aneuploid IVF embryos supports euploid embryo transfer during infertility treatments, and may specifically highlight an explanation for the compromised implantation potential in monosomy embryos. PMID- 27271038 TI - Energy drinks consumption in Italian adolescents: preliminary data of social, psychological and behavioral features. AB - BACKGROUND: To investigate the prevalence of energy drink (ED) consumption and the associations with social, psychological and behavioral features among an Italian adolescent sample. METHODS: A cross-sectional prevalence study of 450 Italian adolescents attending middle school was conducted. The Italian versions of the European Food Safety Authority's adolescent Energy Drinks Questionnaire and of the Depression and Anxiety in Youth Scale (DAYS) were administered to evaluate ED use and its psychological correlates. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using a logistic model to estimate the associations between ED consumption and socio-demographic characteristics, psychological factors and risky behaviors. RESULTS: The prevalence of ED consumers was 57%, of whom 49% used alcohol mixed with ED. A total of 9% exhibited high chronic consumption, 31% average chronic consumption and 8% high acute consumption. Males were significantly more likely to use ED (OR:2.7, 95%CI: 1.8-4.0, p=0.00) and to engage in high acute consumption (OR:4.0, 95%CI: 1.1 13.8, p=0.03). Regular smoking was associated with ED use (OR:3.4, 95%CI: 1.2 9.1, p=0.02). No relationship was observed between ED use and depression (OR:1.6, 95%CI: 0.9-3.0, p=0.10) and anxiety (OR:0.8, 95%CI: 0.5-1.4, p=0.44), although those who were depressed with a suggestive but not statistically significant increased risk of acute ED use (OR: 2.7, 95%CI: 1.0-7.4, p=0.06). CONCLUSIONS: The prevalence of ED consumption among middle school Italian students was high and it was associated with another risky behavior, smoking, but not with anxiety or depression. About half of ED consumers used alcohol mixed with ED. PMID- 27271037 TI - The Antsy Social Network: Determinants of Nest Structure and Arrangement in Asian Weaver Ants. AB - Asian weaver ants (Oecophylla smaragdina) are arboreal ants that are known to form mutualistic complexes with their host trees. They are eusocial ants that build elaborate nests in the canopy in tropical areas. A colony comprises of multiple nests, usually on multiple trees, and the boundaries of the colony may be difficult to identify. However, they provide the ideal model for studying group living in invertebrates since there are a definite number of nests for a given substrate, the tree. Here, we briefly examine the structure of the nests and the processes involved in the construction and maintenance of these nests. We have described the spatial arrangement of weaver ant nests on trees in two distinct tropical clusters, a few hundred kilometres apart in India. Measurements were made for 13 trees with a total of 71 nests in the two field sites. We have considered a host of biotic and abiotic factors that may be crucial in determining the location of the nesting site by Asian weaver ants. Our results indicate that tree characteristics and architecture followed by leaf features help determine nest location in Asian weaver ants. While environmental factors may not be as influential to nest arrangement, they seem to be important determinants of nest structure. The parameters that may be considered in establishing the nests could be crucial in picking the evolutionary drivers for colonial living in social organisms. PMID- 27271039 TI - Clinical factors associated with prehospital exacerbation of anaphylaxis in children. AB - BACKGROUND: The severity of anaphylaxis often varies with time. Because prehospital intervention and initial treatment at hospital are affected by changing symptoms, the aim of this study was to determine the clinical factors associated with prehospital remission and exacerbation in the course of anaphylaxis in children. METHODS: Data from medical records on anaphylactic children who were treated for 3 years at Kobe Children's Primary Emergency Medical Center were retrospectively analyzed. Severity of symptoms was evaluated using Sampson's grade (S-G). Patients with increased S-G at the hospital visit from disease onset (worsened group) were compared with those with decreased S-G at the visit (improved group). Uni- and multivariate analyses were performed to identify clinical differences between the groups, with P<0.05 considered statistically significant. RESULTS: Among 115 anaphylactic children who showed S G changes from onset to hospital visit, 43 were assigned to the worsened group and 72 to the improved group. Univariate analysis showed no significant differences in age, sex, history of asthma, prehospital treatment, type of antigen, or period from symptom onset to hospital visit between the groups. However, the time from antigen exposure to symptom onset was significantly longer, and S-G at onset was significantly lower in the worsened group than in the improved group. Multivariate analysis identified time from antigen exposure to symptom onset (odds ratio: 3.89, P<0.01) and S-G at onset (odds ratio: 0.06, P<0.001) as independent predictors of exacerbation. CONCLUSIONS: Anaphylactic children with slower and milder symptoms at onset are more likely to show deterioration. PMID- 27271040 TI - Usefulness of the most popular neurodevelopmental tests in preschool assessment of children born with very low birth weight. AB - BACKGROUND: The aim of our study was multifaceted neurodevelopmental examination of children born prematurely with very low birth weight (VLBW) in order to evaluate the usefulness of popularly used tests. The second aim of the study was exploration of risk and protective factors of neurodevelopmental impairment. METHODS: Eighty-nine VLBW patients were evaluated at the age of 50 months. All children underwent anthropometric measurements and psychomotor tests: functional independence measure scale (WeeFIM), Gross Motor Function Measurement (GMFM), non verbal psychometric evaluation (Leiter test), Developmental Test of Visual Perception (DTVP-2), temperament questionnaire (EAS-C) and children vocabulary test (TSD). RESULTS: Most severe deficits in ex-preterms' neurodevelopment were associated with verbal abilities, visual perception and temper abnormalities. WeeFIM, DTVP-2, Leiter and vocabulary tests' results correlated with each other. The lowest percent of children with deficits in WeeFIM test indicates, that it seems to be the most valuable tool for identification of the most seriously impaired children. Due to the highest percent of children with visual perception deficits, DTVP test seems to be good second choice in assessment of children born prematurely. In motor assessment GMFM appears to be more adequate than cerebral palsy (CP) diagnosis. Almost one fifth of VLBW did not reach 85% in Gross Motor Function Measurement, although only 9% of children had CP. CONCLUSION: Children born with VLBW had deficits in every part of psychometric evaluation. We believe that the most useful tests in assessment VLBW patients are WeeFIM, GMFM and DTVP. Children with severe prematurity complications could require more precise evaluation. PMID- 27271041 TI - Evaluation of knowledge regarding Shaken Baby Syndrome among parents and medical staff. AB - BACKGROUND: Shaken Baby Syndrome (SBS), currently functioning as Abusive Head Trauma (AHT), is a form of violence against children mainly under 2 years of age. The number of SBS might be underestimated, as many cases of violence remain unreported. The aim of the study was evaluation of the state of knowledge of the SBS phenomenon, its scale and diagnostic methods among parents, medical staff and medical students. METHODS: 639 people were examined: 39% of parents, 32,5% medical staff members and 28,5% of medical students. 82% were women. The average age was 34,9 years (SD=9,78). 70% of them had children. The research tool was an anonymous survey. The 34 questions concerned numerous aspects of violence against children as well as knowledge about SBS. RESULTS: According to 90% of the interviewees shaking a baby may be dangerous but 43% have ever heard about shaken baby syndrome. 'SBS is a form of violence' said 88% of respondents but 57% realize that one-time shaking can lead to death and only 19% indicated men as aggressors. 16% of medical staff members did not know how long it takes for the consequences of shaking a baby to be revealed. CONCLUSIONS: Majority of the medical staff members working with children have never heard about SBS. Only half of the surveyed understands the connection of shaking with vision loss or child's death. Among the long-term consequences of shaking a baby the greatest knowledge concerns emotional consequences of shaking. PMID- 27271042 TI - The association of SHANK3 gene polymorphism and autism. AB - BACKGROUND: Autism spectrum disorder (ASD) and Autism are both general terms for a group of complex disorders of brain development. These disorders are characterized by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. Many genes have been shown to be involved in Autism. SHANK3 (SH3 and multiple ankyrin repeat domain 3) is a member of the highly conserved Shank/ProSAP family of synaptic scaffolding proteins. SHANK3 is suggested as a strong candidate gene for the pathogenesis of Autism and its loss results in disruption of synaptic function. The rs9616915 SNP, which directly affects SHANK3 gene function of splicing regulation and protein structure damage, is a non- synonymous SNP (T>C) that found in exon 6, leads to substitution of Isoleucine to Threonine. The present study was aimed to evaluate whether rs9616915 polymorphism of SHANK3 are related with the susceptibility to Autism. METHODS: Samples were obtained from 90 patients diagnosed with Autism and 100 controls subjects and genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The results of this study showed that there is a significant association in genotype distribution between cases and controls (P= 0.0001). RESULTS: Our findings revealed that individuals with TC genotypes were associated with increased risk of Autism disorder (OR=4.35, 95% CI=2.15 - 8.80, P=0.0001) but no significant differences were found in allele distributions (P= 0.1). CONCLUSIONS: In conclusion, our results indicated that the SHANK3 rs9616915 polymorphism is associated with increased risk of Autism. Larger studies with more patients and controls are needed to confirm the results. PMID- 27271043 TI - CXCL10 Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study. AB - Chemokines are involved in the remodeling of the heart; however, their significance as biomarkers in heart failure is unknown. We observed that circulating CXCR3 receptor chemokines CXCL9 and CXCL10 in a rat model of heart failure were increased 1 week after myocardial infarction. CXCL10 was also increased in both remote and infarcted regions of the heart and remained elevated at 16 weeks; CXCL9 was elevated in the remote area at 1 week. In humans, hierarchical clustering and principal component analysis revealed that circulating CXCL10, MIP-1alpha, and CD40 ligand were the best indicators for differentiating healthy and heart failure subjects. Serum CXCL10 levels were increased in patients with symptomatic heart failure as indexed by NYHA classification II through IV. The presence of CXCL10, MIP-1alpha, and CD40 ligand appears to be dominant in patients with advanced heart failure. These findings identify a distinct profile of inflammatory mediators in heart failure patients. PMID- 27271045 TI - Modulate Organic-Metal Oxide Heterojunction via [1,6] Azafulleroid for Highly Efficient Organic Solar Cells. AB - By creating an effective pi-orbital hybridization between the fullerene cage and the aromatic anchor (addend), the azafulleroid interfacial modifiers exhibit enhanced electronic coupling to the underneath metal oxides. High power conversion efficiency of 10.3% can be achieved in organic solar cells using open cage phenyl C61 butyric acid methyl ester (PCBM)-modified zinc oxide layer. PMID- 27271046 TI - Highly Efficient Transfer of Chromosomes to a Broad Range of Target Cells Using Chinese Hamster Ovary Cells Expressing Murine Leukemia Virus-Derived Envelope Proteins. AB - Microcell-mediated chromosome transfer (MMCT) is an essential step for introducing chromosomes from donor cells to recipient cells. MMCT allows not only for genetic/epigenetic analysis of specific chromosomes, but also for utilization of human and mouse artificial chromosomes (HACs/MACs) as gene delivery vectors. Although the scientific demand for genome scale analyses is increasing, the poor transfer efficiency of the current method has hampered the application of chromosome engineering technology. Here, we developed a highly efficient chromosome transfer method, called retro-MMCT, which is based on Chinese hamster ovary cells expressing envelope proteins derived from ecotropic or amphotropic murine leukemia viruses. Using this method, we transferred MACs to NIH3T3 cells with 26.5 times greater efficiency than that obtained using the conventional MMCT method. Retro-MMCT was applicable to a variety of recipient cells, including embryonic stem cells. Moreover, retro-MMCT enabled efficient transfer of MAC to recipient cells derived from humans, monkeys, mice, rats, and rabbits. These results demonstrate the utility of retro-MMCT for the efficient transfer of chromosomes to various types of target cell. PMID- 27271044 TI - G protein-coupled estrogen receptor inhibits the P2Y receptor-mediated Ca(2+) signaling pathway in human airway epithelia. AB - P2Y receptor activation causes the release of inflammatory cytokines in the bronchial epithelium, whereas G protein-coupled estrogen receptor (GPER), a novel estrogen (E2) receptor, may play an anti-inflammatory role in this process. We investigated the cellular mechanisms underlying the inhibitory effect of GPER activation on the P2Y receptor-mediated Ca(2+) signaling pathway and cytokine production in airway epithelia. Expression of GPER in primary human bronchial epithelial (HBE) or 16HBE14o- cells was confirmed on both the mRNA and protein levels. Stimulation of HBE or 16HBE14o- cells with E2 or G1, a specific agonist of GPER, attenuated the nucleotide-evoked increases in [Ca(2+)]i, whereas this effect was reversed by G15, a GPER-specific antagonist. G1 inhibited the secretion of two proinflammatory cytokines, interleukin (IL)-6 and IL-8, in cells stimulated by adenosine 5'-(gamma-thio)triphosphate (ATPgammaS). G1 stimulated a real-time increase in cAMP levels in 16HBE14o- cells, which could be inhibited by adenylyl cyclase inhibitors. The inhibitory effects of E2 or G1 on P2Y receptor induced increases in Ca(2+) were reversed by treating the cells with a protein kinase A (PKA) inhibitor. These results demonstrated that the inhibitory effects of G1 or E2 on P2Y receptor-mediated Ca(2+) mobilization and cytokine secretion were due to GPER-mediated activation of a cAMP-dependent PKA pathway. This study has reported, for the first time, the expression and function of GPER as an anti inflammatory component in human bronchial epithelia, which may mediate through its opposing effects on the pro-inflammatory pathway activated by the P2Y receptors in inflamed airway epithelia. PMID- 27271047 TI - Pediatric forearm fractures with in situ intramedullary implants. AB - PURPOSE: The purpose of this investigation is to present our institutional experience with fractures of the pediatric forearm with in situ intramedullary nails. METHODS: Six patients treated at our institution for forearm fracture with in situ intramedullary implants between 2004 and 2013 were reviewed. Patient demographics, injury and radiographic characteristics, method of treatment, time to union, and complications were collected from the medical record. RESULTS: 485 patients with forearm fractures were treated with intramedullary implants and six patients presented with a fracture with in situ implants (1.2 %). Fractures in all six patients resulted from a second traumatic event after radiographic healing but before implant removal at a mean of 13.0 months from the initial procedure. One patient had an adequately aligned fracture and was treated with casting without reduction. The remaining five patients (83 %) returned to the operating room for treatment. Two patients underwent rod removal and placement of new intramedullary implants, and two patients were treated with rod removal and plating without attempt at closed reduction. One patient underwent closed reduction in the operating room with successful re-bending of the radial implant and replacement of the ulna implant. All patients went on to uncomplicated radiographic union at a mean 3.6 months. CONCLUSIONS: The incidence of fracture of pediatric forearm with in situ intramedullary implants is low. This rare complication can be treated by several different methods, including revision TENS placement, revision to plate fixation, or in situ bending of rods, with the expectation for successful uncomplicated union. PMID- 27271049 TI - Anesthesia and Long-term Major Adverse Cognitive Effects: P-Values and Confidence Intervals Based on Nonrandom Samples Cannot Justify Acceptance of Null Hypotheses. PMID- 27271048 TI - Lactonic Sophorolipids Increase Tumor Burden in Apcmin+/- Mice. AB - Sophorolipids (SL) are amphiphilic biosurfactant molecules consisting of a disaccharide sophorose with one fatty acid at the C1 position and optional acetylation at the C6'and C6" positions. They exist in a closed ring lactonic (LSL) or open acidic (ASL) structure Sophorolipids are produced in crude mixtures in economically viable amounts by the yeast Starmerella bombicola and used in a variety of consumer products. Varying levels of anti- proliferative and anti cancer activity of crude sophorolipid mixtures are described in a number of tumor cell lines in vitro. However, significant inter-study variation exists in the composition of sophorolipid species as well as other biologically active compounds in these mixtures, which makes interpretation of in vitro and in vivo studies difficult. We produced a 96% pure C18:1 lactonic sophorolipid that dose dependently reduces the viability of colorectal cancer, as well as normal human colonic and lung cell lines in vitro. Oral administration of vehicle-only; or lactonic sophorolipids (50 mg/kg for 70 days), to Apcmin+/- mice resulted in an increase in the number (55.5 +/- 3.3 vs 70.50 +/- 7.8: p < 0.05) and size (modal size 2mm vs 4mm) of intestinal polyps. Lactonic administration resulted in a systematic effect via reduced hematocrit (49.5 +/- 1.0 vs 28.2 +/- 2.0 vs: p<0.03) and splenomegaly (0.56 +/- 0.03g vs 0.71 +/- 0.04g; p<0.01) confirming exacerbation of disease progression in this model. PMID- 27271050 TI - Midlife Risk Factors for Impaired Physical and Cognitive Functioning at Older Ages: A Cohort Study. AB - BACKGROUND: Previous studies examined midlife risk factors separately for old-age impaired physical and cognitive functioning. We determined the overlap of risk factors for both domains of functioning within the same setting. METHODS: Biological and behavioral risk factors at age 50 years and cognitive and physical functioning were assessed 18 (SD = 5) years later in the Whitehall II study (N = 6,316). Impaired physical functioning was defined as >=1 limitation on the activities of daily living scale. Impaired cognitive functioning was defined as Mini-Mental State Examination score <27. Two statistical analyses were employed: minimally adjusted analysis (for age, sex, and ethnicity) and mutually adjusted analysis (including all risk factors). Missing data on risk factors were imputed. RESULTS: After confounder adjustment, impaired physical and cognitive functioning at older ages were predicted by hypertension (odds ratios [ORs] 1.80 95% confidence interval [CI] 1.39-2.33 and 1.57 95% CI 1.07-2.31, respectively), poor lung function (1.51 95% CI 1.28-1.78 and 1.31 95% CI 1.08-1.59), and physical inactivity, marginally in the case of cognitive function (1.50 95% CI 1.19-1.90 and 1.27 95% CI 0.99-1.62) at age 50 years. Impaired physical functioning but not cognitive functioning was additionally predicted by depression and higher body mass index (1.72 95% CI 1.46-2.03 and 1.29 95% CI 1.16-1.44, respectively). CONCLUSIONS: Several midlife risk factors are associated with impaired physical and cognitive functioning in old age, supporting a unified prevention policy. Analysis of 12 risk factors at age 50 suggests that strategies targeting physical inactivity, hypertension, and poor lung function will reduce impairments in both cognitive and physical functioning in old age. PMID- 27271052 TI - Lions, tigers, and bears, oh sh!t: Semantics versus tabooness in speech production. AB - While both semantic and highly emotional (i.e., taboo) words can interfere with speech production, different theoretical mechanisms have been proposed to explain why interference occurs. Two experiments investigated these theoretical approaches by comparing the magnitude of these two types of interference and the stages at which they occur during picture naming. Participants named target pictures superimposed with semantic, taboo, or unrelated distractor words that were presented at three different stimulus-onset asynchronies (SOA): -150 ms, 0 ms, or +150 ms. In addition, the duration of distractor presentation was manipulated across experiments, with distractors appearing for the duration of the picture (Experiment 1) or for 350 ms (Experiment 2). Taboo distractors interfered more than semantic distractors, i.e., slowed target naming times, at all SOAs. While distractor duration had no effect on type of interference at -150 or 0 SOAs, briefly presented distractors eliminated semantic interference but not taboo interference at +150 SOA. Discussion focuses on how existing speech production theories can explain interference from emotional distractors and the unique role that attention may play in taboo interference. PMID- 27271051 TI - Characterization of PET/CT images using texture analysis: the past, the present... any future? AB - After seminal papers over the period 2009 - 2011, the use of texture analysis of PET/CT images for quantification of intratumour uptake heterogeneity has received increasing attention in the last 4 years. Results are difficult to compare due to the heterogeneity of studies and lack of standardization. There are also numerous challenges to address. In this review we provide critical insights into the recent development of texture analysis for quantifying the heterogeneity in PET/CT images, identify issues and challenges, and offer recommendations for the use of texture analysis in clinical research. Numerous potentially confounding issues have been identified, related to the complex workflow for the calculation of textural features, and the dependency of features on various factors such as acquisition, image reconstruction, preprocessing, functional volume segmentation, and methods of establishing and quantifying correspondences with genomic and clinical metrics of interest. A lack of understanding of what the features may represent in terms of the underlying pathophysiological processes and the variability of technical implementation practices makes comparing results in the literature challenging, if not impossible. Since progress as a field requires pooling results, there is an urgent need for standardization and recommendations/guidelines to enable the field to move forward. We provide a list of correct formulae for usual features and recommendations regarding implementation. Studies on larger cohorts with robust statistical analysis and machine learning approaches are promising directions to evaluate the potential of this approach. PMID- 27271053 TI - Detailed heart rate variability analysis in athletes. AB - OBJECTIVE: Heart rate variability (HRV) analysis has been used to evaluate patients with various cardiovascular diseases. While the vast majority of HRV studies have focused on pathological states, our study focuses on the less explored area of HRV analysis across different training intensity and sports. We aimed to measure HRV in healthy elite and masters athletes and compare to healthy, but non-athletic controls. METHODS: Time-domain HRV analysis was applied in 138 athletes (male 110, age 28.4 +/- 8.3) and 100 controls (male 56, age 28.3 +/- 6.9) during Holter monitoring (21.3 +/- 3.0 h). RESULTS: All studied parameters were higher in elite athletes compared to controls [SDNN (CI) 225.3 (216.2-234.5) vs 158.6 (150.2-167.1) ms; SDNN Index (CI) 99.6 (95.6-103.7) vs 72.4 (68.7-76.2) ms; pNN50 (CI) 24.2 (22.2-26.3) vs 14.4 (12.7-16.3) %; RMSSD (CI) 71.8 (67.6-76.2) vs 50.8 (46.9-54.8) ms; p < 0.001]. Masters had higher HRV values than controls, but no significant differences were found between elite athletes and masters athletes. Some parameters were higher in canoeists-kayakers and bicyclists than runners. Lower cut-off values in elite athletes were SDNN: 147.4 ms, SDNN Index: 66.6 ms, pNN50: 9.7 %, RMSSD: 37.9 ms. INTERPRETATION: Autonomic regulation in elite athletes described with HRV is significantly different than in healthy controls. Sports modality and level of performance, but not age- or sex-influenced HRV. Our study provides athletic normal HRV values. Further investigations are needed to determine its role in risk stratification, optimization of training, or identifying overtraining. PMID- 27271054 TI - Thrombotic risk correlates with mutational status in true essential thrombocythemia. AB - BACKGROUND: True essential thrombocythemia (ET) may carry one of the known driver mutations (JAK2, MPL and CALR) or none of them [in triple-negative (3NEG) cases]. The patients' mutational status seems to delineate the clinical manifestations of ET. MATERIALS AND METHODS: We report the data of 183 patients diagnosed with ET strictly according to the WHO 2008 criteria and with a full molecular diagnosis, including the following: 114 patients (62.3%) with JAK2V617F; 25 (13.7%) with CALR type 1 and 19 (10.4%) with CALR type 2; 3 (1.6%) with MPL; 22 (12%) who were 3NEG. Thrombotic risk was assessed by means of the IPSET-thrombosis score (IPSET T). RESULTS: CALR and 3NEG patients had lower haemoglobin levels and leucocyte count than JAK2 patients. CALR patients, and those with type 2 in particular, had higher mean platelet counts and had extreme thrombocytosis more often than any of the other groups. Based on their IPSET-T stratification, 3NEG- and CALR-mutated patients belonged more frequently to the low-risk group and had a significant more favourable thrombosis-free survival rate than those with JAK2 mutation. CONCLUSION: These findings indicate that the three different molecular markers have a significant impact on the clinical course of true ET, giving rise to different phenotypes of the same disease. PMID- 27271055 TI - Ovarian proteomic study reveals the possible molecular mechanism for hyperprolificacy of Small Tail Han sheep. AB - Small Tail Han sheep is a widely bred farm animal in China which has attracted lots of attention due to their high prolificacy and year-round estrus. However, the molecular mechanism of its fecundity remains unrevealed. The FecB gene polymorphism has been found to be associated with the ovulation rate and litter size of sheep. In the present study, we constructed an iTRAQ-based quantitative proteomics analysis to compare the ovarian proteomes of FecB+FecB+ genotype Small Tail Han sheep ewes (Han ++), FecB(B)FecB(B) Han ewes (Han BB) and Dorset ewes (Dorset). Hundreds of differentially expressed proteins between each two groups were identified; GO and KEGG pathway analysis indicated that the expressions of those proteins involved in ribosome assembly, protein translation and mTOR pathway between Dorset and both Han groups were highly different. Between Han ++ and Han BB groups, higher level of protein expressions were related to mitochondrial oxidation functions such as oxidoreductase activity, cytochrome-c oxidase activity and electron carrier activity. This was identified in Han BB group, which may contribute to the elevated ovulation rate of Han BB ewes. In conclusion, our work provided a prospective understanding of the molecular mechanism for high prolificacy of Small Tail Han sheep. PMID- 27271056 TI - Combination inhaled steroid and long-acting beta2-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease. AB - BACKGROUND: The long-acting bronchodilator tiotropium and single-inhaler combination therapy of inhaled corticosteroids and long-acting beta2-agonists (ICS/LABA) are commonly used for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than administering the individual components. OBJECTIVES: To assess relative effects of the following treatments on markers of exacerbations, symptoms, quality of life and lung function in patients with COPD.* Tiotropium plus LABA/ICS versus tiotropium.* Tiotropium plus LABA/ICS versus LABA/ICS. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of Trials (April 2015), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal and reference lists of relevant articles. SELECTION CRITERIA: We included parallel, randomised controlled trials (RCTs) lasting three months or longer conducted to compare ICS and LABA combination therapy in addition to inhaled tiotropium versus tiotropium alone or combination therapy alone. DATA COLLECTION AND ANALYSIS: We independently assessed trials for inclusion, then extracted data on trial quality and outcome results. We contacted study authors to ask for additional information. We collected trial information on adverse effects. MAIN RESULTS: Tiotropium plus LABA/ICS versus tiotropiumWe included six studies (1902 participants) with low risk of bias that compared tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy versus tiotropium alone. Investigators found no statistically significant differences in mortality between treatments (odds ratio (OR) 1.80, 95% confidence interval (CI) 0.55 to 5.91; two studies; 961 participants), a reduction in all cause hospitalisations with the use of combined therapy (tiotropium + LABA/ICS) (OR 0.61, 95% CI 0.40 to 0.92; two studies; 961 participants; number needed to treat for an additional beneficial outcome (NNTB) 19.7, 95% CI 10.75 to 123.41). The effect on exacerbations was heterogeneous among trials and was not meta analysed. Health-related quality of life measured by St. George's Respiratory Questionnaire (SGRQ) showed a statistically significant improvement in total scores with use of tiotropium + LABA/ICS compared with tiotropium alone (mean difference (MD) -3.46, 95% CI -5.05 to -1.87; four studies; 1446 participants). Lung function was significantly different in the combined therapy (tiotropium + LABA/ICS) group, although average benefit with this therapy was small. None of the included studies included exercise tolerance as an outcome.A pooled estimate of these studies did not show a statistically significant difference in adverse events (OR 1.16, 95% CI 0.92 to 1.47; four studies; 1363 participants), serious adverse events (OR 0.86, 95% CI 0.57 to 1.30; four studies; 1758 participants) and pneumonia (Peto OR 1.62, 95% CI 0.54 to 4.82; four studies; 1758 participants). Tiotropium plus LABA/ICS versus LABA/ICSOne of the six studies (60 participants) also compared combined therapy (tiotropium + LABA/ICS) versus LABA/ICS therapy alone. This study was affected by lack of power; therefore results did not allow us to draw conclusions for this comparison. AUTHORS' CONCLUSIONS: In this update, we found new moderate-quality evidence that combined tiotropium + LABA/ICS therapy compared with tiotropium plus placebo decreases hospital admission. Low-quality evidence suggests an improvement in disease specific quality of life with combined therapy. However, evidence is insufficient to support the benefit of tiotropium + LABA/ICS for mortality and exacerbations (moderate- and low-quality evidence, respectively). Of note, not all participants enrolled in the included studies would be candidates for triple therapy according to current international guidance.Compared with the use of tiotropium plus placebo, tiotropium + LABA/ICS-based therapy does not increase undesirable effects such as adverse events or serious non-fatal adverse events. PMID- 27271057 TI - Biodegradable Mg-Cu alloys with enhanced osteogenesis, angiogenesis, and long lasting antibacterial effects. AB - A series of biodegradable Mg-Cu alloys is designed to induce osteogenesis, stimulate angiogenesis, and provide long-lasting antibacterial performance at the same time. The Mg-Cu alloys with precipitated Mg2Cu intermetallic phases exhibit accelerated degradation in the physiological environment due to galvanic corrosion and the alkaline environment combined with Cu release endows the Mg-Cu alloys with prolonged antibacterial effects. In addition to no cytotoxicity towards HUVECs and MC3T3-E1 cells, the Mg-Cu alloys, particularly Mg-0.03Cu, enhance the cell viability, alkaline phosphatase activity, matrix mineralization, collagen secretion, osteogenesis-related gene and protein expressions of MC3T3-E1 cells, cell proliferation, migration, endothelial tubule forming, angiogenesis related gene, and protein expressions of HUVECs compared to pure Mg. The favorable osteogenesis and angiogenesis are believed to arise from the release of bioactive Mg and Cu ions into the biological environment and the biodegradable Mg Cu alloys with osteogenesis, angiogenesis, and long-term antibacterial ability are very promising in orthopedic applications. PMID- 27271059 TI - Racial Disparities in Low Birthweight Risk: an Examination of Stress Predictors. AB - OBJECTIVE: This paper describes racial disparities in low birthweight (LBW) risk between Black women and White women and examines the relationship between race and stressors such as socioeconomic factors, access to health care, and social and health characteristics. METHODS: We analyzed data from the National Survey of Family Growth dataset collected in the USA between 2006 and 2010 (N = 1516). Multivariate logistic regression models were performed. RESULTS: Prevalence of LBW was 5.6 % for pregnancies among White women and 12.2 % among Black women. Black women who had a LBW baby had a lower socioeconomic status (e.g., received assistance to pay for delivery of the baby and public assistance in the prior year). Black women who had a LBW baby were more likely to have reported having good health compared with White women (67.8 vs. 45.1 %, p < .10). Pregnancies of Black women were 2.6 times more likely (odds ratio (OR) = 2.33; 95 % confidence interval (CI), 1.12-6.04) to result in a LBW baby than pregnancies among White women. Pregnancies of women in the income group of 300 % or higher than the poverty level were less likely to be associated with a LBW baby than those among women in the 150-299 % income group (p < .10). Obese women were less likely to have LBW children than those who were underweight or normal weight (p < .10). Among pregnancies of White mothers (n = 943), the only significant variable was self-reported health status. White women who reported having poorer health were 3.7 times more likely to have LBW than those who reported having better health (p < .10). Among Black mothers, the only predictor that was negatively associated with an increased likelihood of having a LBW baby was the SES stressor related to receiving public assistance. CONCLUSION: Racial differences between Black and White women were observed in LBW risk based on socioeconomic factors. We analyzed a large number of stressors, but racial differences remained even after taking these stressors into account. Future policies and research should continually address these differences to decrease LBW risk within and across racial groups. PMID- 27271058 TI - Academic-Community Partnership to Develop a Patient-Centered Breast Cancer Risk Reduction Program for Latina Primary Care Patients. AB - This collaborative study sought to address Latina breast cancer (BC) disparities by increasing health literacy (HL) in a community health center situated on the US-Mexico border region of San Diego County. An academic-community partnership conducted formative research to develop a culturally tailored promotora-based intervention with 109 individuals. The Spanish language program, entitled Nuestra Cocina: Mesa Buena, Vida Sana (Our Kitchen: Good Table, Healthy Life), included six sessions targeting HL, women's health, BC risk reduction, and patient provider communication; sessions include cooking demonstrations of recipes with cancer-risk-reducing ingredients. A pilot study with 47 community health center Latina patients was conducted to examine the program's acceptability, feasibility, and ability to impact knowledge and skills. Pre- and post-analyses demonstrated that participants improved their self-reported cancer screening, BC knowledge, daily fruit and vegetable intake, and ability to read a nutrition label (p < 0.05). Results of the pilot study demonstrate the importance of utilizing patient-centered culturally appropriate noninvasive means to educate and empower Latina patients. PMID- 27271060 TI - Diabetes Health Literacy Among Somali Patients with Diabetes Mellitus in a US Primary Care Setting. AB - PURPOSE: The purpose of this study was to describe diabetes literacy among Somali immigrants with diabetes and its association with diabetes outcomes. Among Somali immigrants in North America, the prevalence of diabetes exceeds that of the general population, and their measures of diabetes control are suboptimal when compared with non-Somali patients. Diabetes literacy is an important mediator of diabetes outcomes in general populations that has not been previously described among Somali immigrants and refugees. METHODS: Diabetes literacy was measured using a translated version of the spoken knowledge in low literacy in diabetes (SKILLD) scale among Somali immigrants and refugees with type 2 diabetes. Diabetes outcome measures, including hemoglobin A1C, low-density lipoprotein (LDL) cholesterol, and blood pressure, were obtained for each patient. Multivariate logistic regression was used to assess associations between diabetes literacy and diabetes outcomes. RESULTS: Among 50 Somali patients with diabetes who completed the survey, the mean SKILLD score was low (42.2 %). The diabetes outcome measures showed a mean hemoglobin A1C of 8 %, LDL cholesterol of 99.17 mg/dL (2.57 mmol/L), systolic blood pressure of 130.9 mmHg, and diastolic blood pressure of 70.2 mmHg. There was no association between diabetes literacy scores and diabetes outcome measures. DISCUSSION: Somali patients with diabetes mellitus had low diabetes literacy and suboptimal measures of diabetes disease control. However, we found no association between diabetes literacy and diabetes outcomes. Future work aimed at reduction of diabetes-related health disparities among Somali immigrants and refugees to high-income countries should go beyond traditional means of patient education for low-literacy populations. PMID- 27271061 TI - Patient-Provider Social Concordance and Health Outcomes in Patients with Type 2 Diabetes: a Retrospective Study from a Large Federally Qualified Health Center in Connecticut. AB - OBJECTIVE: This study was conducted to better understand the relationship between patient-provider social concordance and cardiovascular risk factor control in patients with type 2 diabetes. METHODS: A retrospective study was conducted on adult patients with type 2 diabetes receiving care at Community Health Center, Inc. between July 1, 2012, and June 30, 2013. We utilized a composite score comprised of four social dimensions-age, gender, language, and race/ethnicity-to determine patient-provider social concordance (SC) and used binary logistic regression to relate SC and other potentially influential covariates with cardiovascular outcomes of interest (HgA1c, LDL, BP control). RESULTS: Patients were more likely to have uncontrolled BP if they were in low or medium SC dyads with their providers (OR = 0.689, 95 % CI = 0.480, 0.989; OR = 0.673, 95 % CI 0.486, 0.931), and they were more likely to have controlled BP and LDL in the setting of care continuity with a regular provider (OR = 1.069, 95 % CI 1.005, 1.136; OR = 1.113, 95 % CI 1.048, 1.182). CONCLUSIONS: Certain health outcomes may be susceptible to patient-provider social concordance or discordance. Continuity of care may serve a protective role in offsetting effects of patient provider social mismatching. PMID- 27271062 TI - SEALS: an Innovative Pipeline Program Targeting Obstacles to Diversity in the Physician Workforce. AB - OBJECTIVE: Medical schools may find implementing pipeline programs for minority pre-medical students prohibitive due to a number of factors including the lack of well-described programs in the literature, the limited evidence for program development, and institutional financial barriers. Our goals were to (1) design a pipeline program based on educational theory; (2) deliver the program in a low cost, sustainable manner; and (3) evaluate intermediate outcomes of the program. METHODS: SEALS is a 6-week program based on an asset bundles model designed to promote: (1) socialization and professionalism, (2) education in science learning tools, (3) acquisition of finance literacy, (4) the leveraging of mentorship and networks, and (5) social expectations and resilience, among minority pre-medical students. This is a prospective mixed methods study. Students completed survey instruments pre-program, post-program, and 6 months post-program, establishing intermediate outcome measures. RESULTS: Thirteen students matriculated to SEALS. The SEALS cohort rated themselves as improved or significantly improved when asked to rate their familiarity with MCAT components (p < 0.01), ability to ask for a letter of recommendation (p = 0.04), and importance of interview skills (p = 0.04) compared with before the program. Over 90 % of students referenced the health disparities lecture series as an inspiration to advocate for minority health. Six-month surveys suggested that SEALS students acquired and applied four of the five assets at their college campuses. CONCLUSIONS: This low-cost, high quality, program can be undertaken by medical schools interested in promoting a diverse workforce that may ultimately begin to address and reduce health care disparities. PMID- 27271063 TI - Disparity in Breast Cancer Late Stage at Diagnosis in Missouri: Does Rural Versus Urban Residence Matter? AB - INTRODUCTION: Despite the fact that black women have a lower incidence of breast cancer compared to white women, black women experience higher death rates than any other group. We examined the stage of breast cancer presentation by race and geographic region using population-based breast cancer incidence in all 115 counties in the state of Missouri. METHODS: We used 2003-2008 breast cancer incidence data from Missouri Cancer Registry and Research Center. County of residence was categorized as urban or rural using the rural-urban continuum code. We computed the conditional proportion of stage at diagnosis by race and metropolitan status and also used Pearson's chi-squared test with Yates' continuity correction to determine statistical significance of association. RESULTS: Results of the study indicate that a greater proportion of black women (38.8 %) compared to white women (30.2 %) were diagnosed with more advanced breast metastasis. Our results further suggest that stage at diagnosis depended on county of residence or metropolitan status (p = .04). Women living in non metropolitan counties were slightly more likely to have late-stage breast cancer than their metropolitan counterparts (32.0 vs 30.7 %). Overall, black women had 1.5-fold increased odds of late-stage breast cancer diagnosis compared to their white counterparts (OR = 1.50; 95 % CI, 1.39, 1.63; p < 0.0001). While the odds of late diagnosis among women living in non-metropolitan or rural counties was over 11 % higher compared with their metropolitan or urban counterpart. CONCLUSION: The current study corroborates previous findings that the risk of late-stage breast cancer diagnosis was higher among women residing in non metropolitan rural counties. PMID- 27271064 TI - The Relationships of Demographic Characteristics with Diabetes Biomarkers and Physical Activity Adherence in African American Adults. AB - OBJECTIVE: The objective of this study was to examine the relationships of demographic characteristics with diabetes biomarkers and physical activity adherence in African American adults with type 2 diabetes mellitus. METHODS: Data for this secondary analysis were collected in a controlled trial conducted at an ambulatory internal medicine clinic located in a mid-sized metropolitan area in the southeastern USA. Demographic information was obtained at baseline for all participants receiving a motivational interviewing intervention. Diabetes biomarkers and physical activity adherence were measured at baseline and 3-month follow-up. RESULTS: Being female, older, and having a higher education significantly predicted a decrease in serum glucose over time. Being female and older significantly predicted a slower decrease in body mass index over time. Being younger and more educated significantly predicted probability of improved physical activity adherence. CONCLUSION: Although older African American women had a significant decrease in serum glucose over time, they experienced a slower decrease in their body mass indices and were less likely to adhere to physical activity recommendations. Specific attention should be paid to the demographic characteristics of African Americans with type 2 diabetes mellitus in order to promote optimal clinical outcomes in this vulnerable population. This approach to treatment planning opens a window into the micro-level processes by which social determinants lead to a better response to treatment. PMID- 27271065 TI - Medical Students' Experiences and Perspectives on Interpreting for LEP Patients at Two US Medical Schools. AB - THEORY: Language concordance between patient and provider has been shown to improve health outcomes for Limited English Proficiency (LEP) patients. However, health care teams often use available ad hoc interpreters without knowing whether their language skills are adequate. Little is known about the role of medical students working as ad hoc interpreters. HYPOTHESIS: Bilingual medical students are engaged as interpreters in the care of LEP patients and may serve as a potential resource for health care teams caring for LEP patients. METHOD: We conducted a multi-institutional online survey of graduating medical students at the University of Illinois and the University of Chicago in 2011 and 2012, containing both qualitative and quantitative questions regarding their experiences as interpreters for LEP patients. RESULTS: Half (216/430) of contacted students completed the survey; 40 % (87/216) of responding students reported being bilingual. Of these students, the vast majority, 84 % (73/87), had been asked to interpret for patients in the clinical setting. Only 12 % (10/87) of students reported having felt uncomfortable interpreting for patients "often" or "very often." Over half (53 %, 46/87) described incidents during which they felt uncomfortable interpreting. Seventeen (17/46, 37 %) students described those incidents as high-stakes clinical settings. CONCLUSIONS: Medical schools and health care institutions should establish guidelines for students who identify as fluent in another language and are interested in interpreting for LEP patients in clinical settings, to protect both students and patients when language poses a barrier to quality care. PMID- 27271066 TI - Racial Identity and Mental Well-Being: The Experience of African American Medical Students, A Report from the Medical Student CHANGE Study. AB - PURPOSE: Diversification of the physician workforce continues to be a national priority; however, a paucity of knowledge about the medical school experience for African American medical students limits our ability to achieve this goal. Previous studies document that African American medical students are at greater risk for depression and anxiety. This study moves beyond these findings to explore the role of racial identity (the extent to which a person normatively defines her/himself with regard to race) and its relationship to well-being for African American medical students in their first year of training. METHODS: This study used baseline data from the Medical Student Cognitive Habits and Growth Evaluation (CHANGE) Study; a large national longitudinal cohort study of 4732 medical students at 49 medical schools in the US racial identity for African American students (n = 301) was assessed using the centrality sub-scale of the Multidimensional Inventory of Black Identity. Generalized linear regression models with a Poisson regression family distribution were used to estimate the relative risks of depression, anxiety, and perceived stress. RESULTS: First year African American medical students who had lower levels of racial identity were less likely to experience depressive and anxiety symptoms in their first year of medical school. After controlling for other important social predictors of poor mental health (gender and SES), this finding remained significant. CONCLUSIONS: Results increase knowledge about the role of race as a core part of an individual's self-concept. These findings provide new insight into the relationship between racial identity and psychological distress, particularly with respect to a group of high-achieving young adults. PMID- 27271067 TI - Persisting Racial Disparities in Total Shoulder Arthroplasty Utilization and Outcomes. AB - OBJECTIVE: The purpose was to study whether racial disparities in total shoulder arthroplasty (TSA) utilization and outcomes have declined over time. METHODS: We used the US Nationwide Inpatient Sample from 1998 to 2011. We used chi-squared test to compare characteristics, Cochran-Armitage test to compare utilization rates, and Cochran-Armitage test and logistic regression to compare time-trends in outcomes by race. RESULTS: From 1998 to 2011, 176,141 Whites and 7694 Blacks underwent TSA. Compared to Whites, Blacks who underwent TSA were younger (69.1 vs. 64.2 years; p < 0.0001), more likely to be female (54.9 vs. 71.0 %; p < 0.0001), and have rheumatoid arthritis or avascular necrosis as the underlying diagnosis (1.7 vs. 3.0 % and 1.7 vs. 6.1 %; p < 0.0001 for both) and a Deyo Charlson index of 2 or higher (8.5 vs. 16.7 %; p < 0.0001). Compared to Whites, Blacks had much lower TSA utilization rate/100,000 in 1998 (2.97 vs. 0.83; p < 0.0001) and in 2011 (12.27 vs. 3.33; p < 0.0001); racial disparities increased from 1998 to 2011 (p < 0.0001). A higher proportion of Blacks than Whites had a hospital stay greater than median in 1998-2000, 62 vs. 51.4 % (p = 0.02), and in 2009-2011, 34.4 vs. 27.3 % (p < 0.0001); disparities did not change over time (p = 0.31). These disparities in utilization were borderline significant in adjusted analyses. There were no racial differences in proportion discharged to inpatient medical facility in 1998-2000, 15.2 vs. 15.0 % (p = 0.95), and in 2009-2011, 12.3 vs. 11.1 % (p = 0.37), respectively. CONCLUSIONS: We found increasing racial disparities in TSA utilization. Some disparities in outcomes exist as well. Patients, surgeons, and policy-makes should be aware of these findings and take action to reduce racial disparities. PMID- 27271068 TI - Considerations of Methodological Approaches in the Recruitment and Retention of Immigrant Participants. AB - OBJECTIVE: This study aims to identify effective strategies related to recruitment and retention of immigrant survey participants. METHODOLOGY: The study used a multi-mode approach in, first, conducting a literature review of recent articles on surveys that either targeted immigrants or included large numbers of immigrants in their samples. Next, six surveys were reviewed that either targeted or included large numbers of immigrants. Finally, expert opinions on immigration were gathered regarding recruitment and retention of immigrant survey participants. RESULTS: Although immigrants may be difficult to recruit due to limited English proficiency, mistrust of strangers, and/or high mobility, many of these challenges can be overcome by adopting the same strategies used when surveying ethnically diverse populations (e.g., snowballing versus advertisement, establishing a personal connection with data collectors). Nonetheless, a few practices were identified as most relevant for recruitment and retention of immigrant populations, including involving local community organizations relevant to immigrants, translation of materials tailored to the vernacular language of the various ethnicities, and customizing non-monetary incentives to the specific ethnicity. CONCLUSIONS: Based on the reviews and expert interviews, multiple strategies have been shown to be effective in recruiting and retaining immigrant participants. PMID- 27271070 TI - The Social Environment and Childbearing Expectations: Implications for Strength Based Sexual Health Interventions for Latino Youth. AB - In the United States, adolescent childbearing is disproportionately higher among Latino youth, a growing population facing substantial social exclusion. Exploring the relationship between the social environment and sexual health outcomes among Latino youth may offer insights into the development of novel interventions. In this study, Latino youth in partnerships were recruited from neighborhood venues in San Francisco and completed in-depth interviews. Youth reported a desire to complete higher education goals prior to starting a family to improve future opportunities and further personal development. Youth stated that social network members, family and partners, were supportive of their individual childbearing expectations. Social environment barriers tied to poverty, immigration status, and gang violence hindered educational attainment. Some differences were noted by gender and immigrant generation. Building on protective social ties and creating avenues in poor, urban neighborhoods for Latino youth to fully access educational opportunities may counter early childbearing and improve sexual health. PMID- 27271069 TI - Factors Associated with HPV Vaccine Awareness in a Population-Based Sample of Hispanic Women in Puerto Rico. AB - OBJECTIVES: The objective of this study was to investigate the factors associated with HPV awareness among women aged 16 to 64 years, among underserved minority Hispanic women living in Puerto Rico. METHODS: A population-based, cross sectional sample of 566 women, ages 16 to 64 years, living in the San Juan metropolitan area were surveyed regarding sexual behavior, HPV knowledge, and HPV vaccine uptake. Data was analyzed using descriptive statistics and multivariate logistic regression. RESULTS: Overall, 64.8 % of the women in the sample had heard about the HPV vaccine. Among those in the recommended catch-up vaccination age range (16-26 years, n = 86), 4.7 % had received at least one dose of the HPV vaccine. Of those aware of the availability of the HPV vaccine, most had learned about it through the media, whereas, only 39.6 % had learned about it from a physician. Multivariate logistic regression analysis showed that HPV awareness (OR 8.6; 95 % CI 5.0-14.8) and having had an abnormal Pap smear (OR 2.0; 95 % CI 1.2-3.4) were associated with HPV vaccine awareness (p < 0.05). CONCLUSION: HPV vaccine awareness among Hispanic women in the San Juan metropolitan area of Puerto Rico continues to be low. Strong recommendations from physicians and participation in HPV vaccine educational efforts are essential if the rate of HPV vaccination is to increase in the targeted population. Compared to the USA, and to their US Hispanic counterparts, a health disparity with regard to HPV vaccine awareness and coverage is evident in Puerto Rico; targeted action to deal with this disparity is urgently needed. PMID- 27271071 TI - Disparities in Health, Health Care Access, and Life Experience Between American Indian and White Adults in South Dakota. AB - OBJECTIVES: The objective of this study is to investigate the factors associated with depressive symptoms and chronic illnesses in American Indians compared with White adults born in the post-World War II period, 1946 to 1964, and living in South Dakota. DESIGN: A cross-sectional design of American Indian and White adults aged 50 and older in South Dakota (Brookings, Vermillion, Sioux Falls, and all others areas of South Dakota) between January 2013 and May 2013 was used. American Indian and White adults (born between 1946 and 1964; N = 349). Data included sociodemographic factors and measures of chronic physical health condition, health care access, adverse childhood experiences, body mass index (BMI), Alcohol Use Disorders Identification Test, Technology Acceptance Model, and Multidimensional Scale of Perceived Social Support and Depressive Symptoms. RESULTS: American Indian adults reported more chronic diseases and conditions, a lower self-perceived physical health, were more likely to be overweight or obese, had more adverse childhood experience (ACE), and reported a lower level of alcohol intake compared to White adults. BMI was significantly associated with an increased number of chronic conditions for both groups, and American Indians' better perception of their physical health was significantly associated with lower total number of chronic conditions. Self-perceived mental health, a better level of access to health care, and a higher degree of social support were significantly inversely associated with the number of depressive symptoms for American Indian adults, while a greater level of ACE was significantly associated with an increased number of depressive symptoms for this group. CONCLUSION: The current study not only support previous studies but also contributes to understanding the disparities in and risk factors potentially impacting American Indians' physical and mental health. Our findings highlight the need to investigate the American Indians' perceptions and knowledge about health care accessibility including availability as well as perceived barriers including social sensitivity and trust. Health professionals might need to pay attention to BMI, ACE, and social relationship among American Indian adults to improve physical and mental health. PMID- 27271072 TI - Racial/Ethnic Differences in the Use of Primary Care Providers and Preventive Health Services at a Midwestern University. AB - Many universities seek to improve the health and wellbeing of their faculty and staff through employer wellness programs but racial/ethnic disparities in health care use may still persist. The purpose of this research was to identify racial/ethnic disparities in the use of preventive health services at a Midwestern university. A record review was conducted of self-reported health data from University employees, examining the use of primary care and common screening procedures collected in a Personal Health Assessment conducted by the University's wellness program. Results show that there were significant racial/ethnic differences in the use of primary care and participation in screening. Notably, Asian employees in this sample were less likely to have a primary care provider and participate in routine cancer screenings. The observed racial/ethnic differences in screening behavior were mediated by the use of primary care. Together, these data show that despite equal access to care, racial and ethnic disparities in screening persist and that having a primary care provider is an important predictor of screening behavior. Results suggest that health communications designed to increase screening among specific racial/ethnic minority groups should target primary care use. PMID- 27271073 TI - African-American Parents' Knowledge and Perceptions About BMI Measurements, School-Based BMI Screening Programs, and BMI Report Cards: Results from a Qualitative Investigation and Implications for School-to-Parent Communication. AB - School-based body mass index (BMI) screenings can help parents make informed decisions about their child's health, but schools have questioned parents' understanding and attitudes about BMI measures and report cards. Although researchers have investigated minority parents' perceptions of their child's weight, no research has explored minority parents' knowledge and perceptions related to BMI measurements, school-based BMI screening programs, and BMI report cards. To address this gap, focus groups were conducted (n = 20) with female Black or African-American parents/guardians from a large urban school district. Participants were asked to share their perceptions before and after receiving education about BMI measurements and screening programs. Pre-education: Many participants had heard of BMI, thought it was similar to body fat, believed screenings were intended to track students' weights and monitor eating habits, and were concerned that screenings could cause their child embarrassment. Post education: Most participants did not object to screenings, but said they would have without education about why and how BMI measurements are taken. They also voiced concerns about lack of prior notice, confidentiality, and the need for schools to serve healthier food. Some of these findings support those of other qualitative studies of parents' concerns about BMI screenings, but no previous studies have compared parents' perceptions of screening programs pre-/post education. The results reinforce that schools' efforts to explain what BMI measurements are as well as why and how they are taken can increase parents' confidence in the schools and level of comfort with BMI screening programs and report cards. PMID- 27271074 TI - Two Worlds of Obesity: Ethnic Differences in Child Overweight/Obesity Prevalence and Trajectories. AB - OBJECTIVES: Research on childhood obesity has examined the prevalence of overweight and obesity during childhood and developmental trajectories. This study focuses on the extent to which Hispanic and non-Hispanic white elementary students differ in prevalence of overweight and obesity by grade level, time, gender, and school setting. It also focuses on comparison of the trajectories in weight status for the Hispanic and non-Hispanic white students. METHODS: BMI values were examined both using standard scores (z-scores) and as categorical variables. Cross-sectional data from 4 years were used to examine prevalence, and panel data across 2-year periods examined trajectories. Descriptive statistics and mixed models, controlling for school setting, were used. RESULTS: Hispanic students began first grade with higher prevalence of obesity and overweight, and the differences were larger in higher grades and later years. The majority of students had stable weight status over the 2-year periods of the trajectory analysis, but Hispanic students began the panel with higher BMI-Z values and were more likely to increase and less likely to decrease BMI-Z. CONCLUSIONS: The findings suggest that the degree of childhood overweight/obesity, especially among Hispanics, is substantial and will likely have profound impacts on adult obesity and other associated health issues in the future. Findings confirm the need for early childhood interventions to influence BMI. PMID- 27271075 TI - Health Care Access, Utilization, and Management in Adult Chinese, Koreans, and Vietnamese with Cardiovascular Disease and Hypertension. AB - BACKGROUND: Asians are often pooled together when evaluating disparities in health care indicators (access, utilization, and management), though substantial variation may exist across different Asian ethnicities. OBJECTIVE: The aim of this study was to compare health care indicators among Chinese, Korean, Vietnamese, and non-Hispanic white (NHW) adults with cardiovascular disease and hypertension (CVD/HTN). METHODS: We analyzed health care indicators using multivariable logistic regression in a sample of Asians and NHWs with CVD/HTN from the 2011-2012 California Health Interview Survey (CHIS). RESULTS: Koreans had the lowest utilization of emergency room (ER) or inpatient hospital services; Vietnamese had the lowest access to a personal doctor; Chinese had the lowest adjusted odds of having seen a doctor in the prior 12 months; and all Asians received fewer written heart disease care plans compared to NHWs. Even when utilization of ER for heart disease appeared to be similar, lack of access to a doctor was a more common reason noted by Asians versus NHWs. However, a lower proportion of Asians reported delays in receiving prescription or care. Accounting for differences across groups did not diminish these disparities. CONCLUSION: Health care indicators varied by race and across Asian ethnicities even after controlling for sociodemographic factors, insurance coverage, and health status. Future studies should consider oversampling other Asian ethnicities and assessing more in depth the potential impact of ethnicity-related factors on disparities in health care indicators. PMID- 27271076 TI - Association Between Stressful Life Events and Depression; Intersection of Race and Gender. AB - BACKGROUND: Although stressful life events (SLEs) and depression are associated, we do not know if the intersection of race and gender modifies the magnitude of this link. Using a nationally representative sample of adults in the USA, we tested if the association between SLE and major depressive episode (MDE) depends on the intersection of race and gender. METHODS: Data came from the National Survey of American Life (NSAL), 2003, a cross-sectional survey that enrolled 5899 adults including 5008 Blacks (African-Americans or Caribbean Blacks), and 891 Non Hispanic Whites. Logistic regression was used for data analysis. Stressful life events (past 30 days) was the independent variable, 12-month MDE was the dependent variable, and age, educational level, marital status, employment, and region of country were controls. RESULTS: In the pooled sample, SLE was associated with MDE above and beyond all covariates, without the SLE * race interaction term being significant. Among men, the SLE * race interaction was significant, suggesting a stronger association between SLE and MDE among White men compared to Black men. Such interaction between SLE * race could not be found among women. CONCLUSIONS: The association between SLE and depression may be stronger for White men than Black men; however, this link does not differ between White and Black women. More research is needed to better understand the mechanism behind race by gender variation in the stress-depression link. PMID- 27271077 TI - Infant Mortality and SIDS Perceptions Among Key Healthcare Professional Informants in Sedgwick County, KS. AB - INTRODUCTION: Sedgwick County, KS, has one of the highest infant mortality rates (IMR) in the USA, of which sudden infant death syndrome (SIDS) is a large component. The purpose of this study was to assess local key informants' awareness of the high IMR overall, their knowledge and beliefs about SIDS risk factors specifically, and their recommendations for ways to increase physician and community awareness of SIDS within Sedgwick County, KS. METHODS: Structured interviews were conducted with key informants from Sedgwick County, KS. RESULTS: Four themes emerged from key informant interviews: low level of awareness of infant mortality and SIDS, target population most at risk for SIDS/infant mortality, and barriers to and importance of SIDS education. Key informants were in consensus that there was a lack of general community awareness surrounding the high IMR in Sedgwick County. Strategies were identified to address this issue, including consistent SIDS education of medical providers and parents, social support to moms, use of social media, and involving the faith community in educating target populations about risk factors. CONCLUSIONS: Health and public health key informants provided an overall view of their perception of the SIDS problem in Sedgwick County, KS. Based on collected interviews, the consensus was there are significant problems within Sedgwick County around the issue of SIDS awareness (severity of the problem), SIDS risk, and barriers to increasing SIDS education among professional and community members. African-Americans were identified as the population with the highest infant mortality and SIDS rates in Sedgwick County by health and public health key informant participants. A concerted, educational approach was recommended as the best way forward to reduce SIDS risk within this community. PMID- 27271078 TI - The Impact of Race on Intensity of Care Provided to Older Adults in the Medical Intensive Care Unit. AB - BACKGROUND: African-Americans and Hispanics receive disproportionately less aggressive non-critical treatment for chronic diseases than their Caucasian counterparts. However, when it comes to end-of-life care, minority races are purportedly treated more aggressively in Medical Intensive Care Units (MICU) and are more likely to die there. OBJECTIVE: We sought to determine the impact of race on the intensity of care provided to older adults in the Medical Intensive Care Unit (MICU) using the Therapeutic Intervention Scoring System-28 (TISS-28) and other MICU interventions. METHODS: This is a prospective study of a cohort of 309 patients aged 60 years and older in the MICU. Interventions such as mechanical ventilation, vasopressors, new onset dialysis, feeding tubes, and pulmonary artery catheterization were recorded. Primary outcomes were TISS-28 scores and MICU interventions. RESULTS: Non-white patients were younger and had more dementia and delirium although there was no difference in ICU mortality. The amount of critical care delivered to non-white and white patients were equivalent at p <= 0.05 based on their respective TISS-28 scores. Non-white patients received more renal replacement therapy than white patients. CONCLUSIONS: Our study adds to the growing body of literature demonstrating that the relationship between race, patient preference, and the intensity of care provided in MICUs is multifaceted. Although prior studies have reported that non-white populations often opt for more aggressive care, the similar proportions of non-white and white "full code" patients in this study suggests that this idea is overly simplistic. PMID- 27271080 TI - The role of the environment in the ion induced fragmentation of uracil. AB - The fragmentation of uracil molecules and pure and nano-hydrated uracil clusters by (12)C(4+) ion impact is investigated. This work focuses on the fragmentation behavior of complex systems and the effect of the environment. On the one hand, it is found that the environment in the form of surrounding uracil or water molecules has a significant influence on the fragmentation dynamics, providing an overall 'protective' effect, while on the other hand we observe the opening of specific fragmentation channels. In particular, we report on the first observation of a series of hydrated fragments. This indicates a strong interaction between uracil and water molecules, holding the water clusters bound to the observed molecular fragments. PMID- 27271079 TI - The Ethno-linguistic Community and Premature Death: a Register-Based Study of Working-Aged Men in Finland. AB - One of the most striking features of premature death in Finland is the ethno linguistic mortality gradient in working-aged men. Finnish speakers have a notably higher mortality risk than Swedish speakers. The underlying reasons are not fully clear, but one suggested explanation has been that the level of social integration is lower in the Finnish-speaking community than that in the Swedish speaking one, as people in the former are geographically less rooted at the local level. In this paper, we derive a proxy for the influence of the ethno-linguistic community as a contextual factor on the Finnish-Swedish mortality gradient. The strategy is based on a unique setup that makes it possible to identify people not only by their ethno-linguistic background and ethno-linguistic affiliation, but we indirectly know also in which community a person has been raised. Results of multivariate regressions provide poor support for this contextual hypothesis, however, and rather suggest that some latent individual characteristics might be important, hence illuminating the complexity behind the excess mortality of Finnish speakers. PMID- 27271081 TI - Immigration Rates during Population Density Reduction in a Coral Reef Fish. AB - Although the importance of density-dependent dispersal has been recognized in theory, few empirical studies have examined how immigration changes over a wide range of densities. In a replicated experiment using a novel approach allowing within-site comparison, we examined changes in immigration rate following the gradual removal of territorial damselfish from a limited area within a much larger patch of continuous habitat. In all sites, immigration occurred at intermediate densities but did not occur before the start of removals and only rarely as density approached zero. In the combined data and in 5 of 7 sites, the number of immigrants was a hump-shaped function of density. This is the first experimental evidence for hump-shaped, density-dependent immigration. This pattern may be more widespread than previously recognized because studies over more limited density ranges have identified positive density dependence at low densities and negative density dependence at high densities. Positive density dependence at low density can arise from limits to the number of potential immigrants and from behavioral preferences for settling near conspecifics. Negative density dependence at high density can arise from competition for resources, especially high quality territories. The potential for non-linear effects of local density on immigration needs to be recognized for robust predictions of conservation reserve function, harvest impacts, pest control, and the dynamics of fragmented populations. PMID- 27271082 TI - Corrigendum: Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4. PMID- 27271083 TI - Time to HAART Initiation after Diagnosis and Treatment of Opportunistic Infections in Patients with AIDS in Latin America. AB - BACKGROUND: Since 2009, earlier initiation of highly active antiretroviral therapy (HAART) after an opportunistic infection (OI) has been recommended based on lower risks of death and AIDS-related progression found in clinical trials. Delay in HAART initiation after OIs may be an important barrier for successful outcomes in patients with advanced disease. Timing of HAART initiation after an OI in "real life" settings in Latin America has not been evaluated. METHODS: Patients in the Caribbean, Central and South America network for HIV Epidemiology (CCASAnet) >=18 years of age at enrolment, from 2001-2012 who had an OI before HAART initiation were included. Patients were divided in an early HAART (EH) group (those initiating within 4 weeks of an OI) and a delayed HAART (DH) group (those initiating more than 4 weeks after an OI). All patients with an AIDS defining OI were included. In patients with more than one OI the first event reported was considered. Calendar trends in the proportion of patients in the EH group (before and after 2009) were estimated by site and for the whole cohort. Factors associated with EH were estimated using multivariable logistic regression models. RESULTS: A total of 1457 patients had an OI before HAART initiation and were included in the analysis: 213 from Argentina, 686 from Brazil, 283 from Chile, 119 from Honduras and 156 from Mexico. Most prevalent OI were Tuberculosis (31%), followed by Pneumocystis pneumonia (24%), Invasive Candidiasis (16%) and Toxoplasmosis (9%). Median time from OI to HAART initiation decreased significantly from 5.7 (interquartile range [IQR] 2.8-12.1) weeks before 2009 to 4.3 (IQR 2.0-7.1) after 2009 (p<0.01). Factors associated with starting HAART within 4 weeks of OI diagnosis were lower CD4 count at enrolment (p-<0.001), having a non-tuberculosis OI (p<0.001), study site (p<0.001), and more recent years of OI diagnosis (p<0.001). DISCUSSION: The time from diagnosis of an OI to HAART initiation has decreased in Latin America coinciding with the publication of evidence of its benefit. We found important heterogeneity between sites which may reflect differences in clinical practices, local guidelines, and access to HAART. The impact of the timing of HAART initiation after OI on patient survival in this "real life" context needs further evaluation. PMID- 27271084 TI - Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency. AB - Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients. PMID- 27271085 TI - Variable-Internal-Stores models of microbial growth and metabolism with dynamic allocation of cellular resources. AB - Variable-Internal-Stores models of microbial metabolism and growth have proven to be invaluable in accounting for changes in cellular composition as microbial cells adapt to varying conditions of nutrient availability. Here, such a model is extended with explicit allocation of molecular building blocks among various types of catalytic machinery. Such an extension allows a reconstruction of the regulatory rules employed by the cell as it adapts its physiology to changing environmental conditions. Moreover, the extension proposed here creates a link between classic models of microbial growth and analyses based on detailed transcriptomics and proteomics data sets. We ascertain the compatibility between the extended Variable-Internal-Stores model and the classic models, demonstrate its behaviour by means of simulations, and provide a detailed treatment of the uniqueness and the stability of its equilibrium point as a function of the availabilities of the various nutrients. PMID- 27271086 TI - Cerebral Microbleeds, Cognition, and Therapeutic Implications. PMID- 27271087 TI - Efficacy and safety of asenapine in Asian patients with an acute exacerbation of schizophrenia: a multicentre, randomized, double-blind, 6-week, placebo controlled study. AB - RATIONALE: Asenapine is a second generation anti-psychotic approved in the USA in 2009 for the treatment of schizophrenia, but its efficacy has not been proven in Asian patients. OBJECTIVES: The objectives of this study are to evaluate the efficacy and tolerability of asenapine in Asian patients experiencing an acute exacerbation of schizophrenia. METHODS: In this prospective, double-blind study, patients in Japan, Korea, and Taiwan were randomized (1:1:1) to asenapine 5 mg twice daily (bid), 10 mg bid or placebo for 6 weeks after a 3- to 7-day washout/screening period. The primary endpoint was the mean change in the positive and negative syndrome scale (PANSS) total score from baseline to day 42/treatment end. RESULTS: Of the 532 participants randomized, 530 received treatment. The primary endpoint was significantly greater with asenapine 5 and 10 mg bid than with placebo (-12.24 and -14.17 vs. -0.95; p < 0.0001). The results of secondary endpoints including PANSS negative subscale scores and PANSS responders at the end of treatment supported the results of the primary endpoint. There were no significant differences in the incidence of treatment-emergent adverse events reported with asenapine 5 and 10 mg bid and placebo (84.6, 80.7, and 81.6 %). There was a mean (+/- standard deviation) change in weight of -1.76 +/- 2.45 kg for placebo, +0.42 +/- 2.65 kg for asenapine 5 mg bid, and +0.81 +/- 2.89 kg for asenapine 10 mg bid group. CONCLUSIONS: Asenapine was effective and generally well tolerated when used for the treatment of acute exacerbations of schizophrenia in Asian patients. PMID- 27271088 TI - Medulloblastoma in adults: they're not just big kids. PMID- 27271089 TI - Performance of 18F-FET-PET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: inherent bias in meta-analysis not revealed by quality metrics. PMID- 27271090 TI - Response to: Performance of 18F-FET-PET versus 18F-FDG-PET for the diagnosis and grading of brain tumors: inherent bias in meta-analysis not revealed by quality metrics. PMID- 27271092 TI - Superficial fibular nerve variations of fascial piercing: A meta-analysis and clinical consideration. AB - The superficial fibular (peroneal) nerve (SFN) is one of the successive branches of the common fibular (peroneal) nerve and goes on to bifurcate into the medial dorsal cutaneous (MDN) and intermediate dorsal cutaneous (IDN) nerves. The SFN is a main contributor to sensory innervation of the foot and lower leg. It varies widely in its penetrance of the deep (crural) fascia, and differences in its subsequent course can result in iatrogenic injuries. Articles on the prevalence of this anatomical variation were identified by a comprehensive database search. The data collected were extracted and pooled into a meta-analysis. A total of 14 articles (n = 665 lower limbs) were included on the meta-analysis of SFN variations in fascial piercing. The normal Type 1 variation, where the SFN pierces the deep fascia as a single entity and later bifurcates into the MDN and IDN, had a pooled prevalence of 82.7% (95%CI: 74.0-89.4). The Type 2 variant, where the SFN bifurcates early and then pierces the fascial layer separately as the MDN and IDN, had a pooled prevalence of 15.6% (95%CI: 8.9-23.6). Type 3, when the SFN penetrates the deep fascia and courses similar to the MDN with absent IDN was noted in 1.8% (95%CI: 0.0-4.9) of cases. A substantial portion of the population has a pattern of SFN piercing that deviates from the normal Type 1 anatomy. It is recommended that possible SFN variants in patients should be addressed thoroughly to help prevent iatrogenic injuries and postoperative complications. Clin. Anat. 30:120-125, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27271093 TI - CBX7 deficiency plays a positive role in dentin and alveolar bone development. AB - To clarify the role of CBX7 deficiency in dentin and alveolar bone development, the dental and mandibular phenotypes of homozygous CBX7-knockout (CBX7(-/-)) mice were compared with their wild-type (WT) counterparts at 3 weeks age. In contrast to WT littermates, dental volume and dentin sialoprotein-positive area were significantly increased, whereas the area ratio of predentin to dentin was decreased markedly in CBX7(-/-) mice. Mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive area, osteoblast number and activity, protein expression and mRNA level of Runt-related transcription factor 2 (Runx2), alkaline phosphatase, osteocalcin, osteopontin and bone morphogenetic protein 2 (BMP2) were all remarkably increased, while osteoclast number and activity, and mRNA expression ratio of NF-kappaB ligand (RANKL) to osteoprotegerin (opg) were all decreased significantly in the alveolar bone of CBX7(-/-) mice compared with their WT counterparts. Moreover, proliferating cell nuclear antigen (PCNA)-positive cells were found more in Hertwig' s epithelial root sheath of CBX7(-/-) mice, and their protein level of cyclin E1, cyclin-dependent kinase 2 (CDK2) were correspondingly increased in contrast to WT mice. Taken together, these results of this study suggest that CBX7 deficiency plays a positive role in dentin and alveolar bone formation. PMID- 27271095 TI - Synthesis and characterization of five-coordinate, 16-electron RuII complexes supported by tridentate bis(phosphino)silyl ligation. AB - The synthesis of 16-electron complexes of the type (Cy-PSiP)RuX(L) (Cy-PSiP = kappa3-(2-Cy2PC6H4)2SiMe) is reported. Treatment of (Cy-PSiP)H with one equiv. RuCl2(PPh3)3 in the presence of Et3N afforded a mixture of (Cy-PSiP)RuCl(PPh3) (1) and [(Cy-PSiP)RuCl]2 (2), which exists in a temperature-dependent equilibrium process involving reversible dissociation of PPh3 from 1 to form 2. While treatment of this equilibrium mixture with PMe3 afforded (Cy-PSiP)RuCl(PMe3) (3) cleanly, this product was more straightforwardly prepared by the addition of PMe3 to 2 (97% yield). Attempts to form an alkyl complex of the type (Cy PSiP)RuMe(PMe3) via treatment of 3 with MeMgBr led to the dehydrogenation and cyclometalation of a cyclohexyl phosphino group to give the isolable 18-electron complex [MeSi(C6H4PCy2)(C6H4PCy(eta3-C6H8))]RuPMe3 (4, 78% yield). The hydrido complex (Cy-PSiP)RuH(PMe3) (5) was identified as a minor by-product in this dehydrogenative process. Whereas simple 16-electron alkyl complexes of the type (Cy-PSiP)RuR(PMe3) remained elusive, the isolable allyl complex (Cy-PSiP)Ru(eta3 C3H5) (9) was successfully prepared from 2 and (C3H5)MgCl (79% yield). Treatment of 3 with Me3SiN3 or NaN3 did not generate a five-coordinate azido species. However, the putative dinuclear complex [(Cy-PSiP)RuN3]2 (10) was observed to react with one equiv. of PMe3 to afford the isolable five-coordinate azido complex (Cy-PSiP)Ru(N3)(PMe3) (11; 94% yield). Crystallographic data for 3, 4, 5, 9 and 11 are presented. PMID- 27271094 TI - The interaction between ApoA2 -265T>C polymorphism and dietary fatty acids intake on oxidative stress in patients with type 2 diabetes mellitus. AB - INTRODUCTION: Apolipoprotein A2 (APOA2) -265T>C polymorphism has been studied in relation to oxidative stress and various dietary fatty acids. Since the interaction between APOA2 polymorphism and dietary fatty acids on oxidative stress has not yet discussed, we aimed to investigate the interaction on oxidative stress in type 2 diabetes mellitus (T2DM) patients. METHODS: The subjects were 180 T2DM patients with known APOA2 genotype, either TT, TC or CC. Superoxide dismutase (SOD) activity was determined by colorimetric method. Total antioxidant capacity (TAC) and serum level of 8-isoprostane F2alpha were measured by spectrophotometry and ELISA, respectively. Dietary intake was collected through a food frequency questionnaire. Based on the median intake, fatty acids intake was dichotomized into high or low groups. The interaction between APOA2 polymorphism and dietary fatty acids intake was analyzed by ANCOVA multivariate interaction model. RESULTS: Higher than median intake of omega-6 polyunsaturated fatty acids (n-6 PUFA) was associated with increased serum level of 8-isoprostane F2alpha in subjects with TT/TC genotype (p = 0.004), and higher than median intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) was associated with increased serum SOD activity in CC genotype (p < 0.001). There was a statistically significant interaction between APOA2 polymorphism and n-6 PUFA intake on 8-isoprostane F2alpha concentration as well as n-3 PUFA intake on serum SOD activity (p-interaction = 0.04 and 0.02, respectively). CONCLUSIONS: The current study shows the interaction between APOA2 polymorphism and dietary fatty acids intake on oxidative stress. More investigations on different populations are required to confirm the interaction. PMID- 27271096 TI - HER2 gene copy number and breast cancer-specific survival. AB - AIMS: HER2 amplification occurs in 10-15% of breast cancers. It is associated with poor breast cancer-specific survival (BCSS) and is an important prognostic and predictive marker. While it has been accepted that the HER2:chromosome 17 centromere (CEP17) ratio determines HER2 status, recent guidelines acknowledge the significance of HER2 copy number alone. The aims of this study were to assess BCSS according to mean HER2 copy number and HER2 status expressed as a HER2:CEP17 ratio with and without increased CEP17 copy number. METHODS AND RESULTS: The study population comprised breast cancer patients treated with surgery only and with long-term follow-up. In situ hybridization for HER2:CEP17 was performed on tissue microarrays and was successful in 679 cases. These were included in the study. Kaplan-Meier methods were used to estimate BCSS. A total of 47 cases had >=4 < 6 HER2 copies; 16 were HER2+ and 31 were HER2- by ratio. Eighty-five cases had >=6 copies of HER2 and only two of these were HER2- by ratio. The risk of death from breast cancer was increased among those with >=6 HER2 compared to cases with 0-3.9 HER2 signals [hazard ratio (HR): 2.05; confidence interval (CI): 1.49-2.82 (unadjusted)]. After adjusting for stage, there was increased risk of death from breast cancer during the first 5 years after diagnosis in cases that were HER2- by ratio but with >=4 < 6 HER2 (HR: 2.38; CI: 1.23-4.60). CONCLUSIONS: Increased copy number of HER2 may confer an increased risk of death from breast cancer despite negative HER2 status by ratio. PMID- 27271097 TI - Maternal and fetal outcomes in oocyte donation pregnancies. AB - BACKGROUND: Since the first successful use of donated oocytes in 1984, the number of oocyte donation cycles in Europe and the USA has dramatically increased. Consequently, there has been increasing interest in the impact of oocyte donation on maternal and fetal outcomes. OBJECTIVE AND RATIONALE: The aim of this review was to summarize the literature regarding maternal and fetal outcomes from pregnancies conceived through oocyte donation. SEARCH METHODS: Identification of relevant publications was through research within the Embase Medline and PubMed databases, the Google-indexed scientific literature and periodic specialized magazines from the on-line Library Service of the University of Milan. OUTCOMES: Oocyte donation seems to be independently associated with a higher rate of pregnancy-induced hypertension and pre-eclampsia. An explanatory hypothesis is that an immunological maladaptation causes placenta-mediated disorders in oocyte donation pregnancies. The risks are even higher in twin pregnancies. Oocyte donation also seems to be associated with lower fetal birthweight. However, after adjusting for obstetric complications, most studies report less pronounced differences in birthweight or no dissimilarities. The incidence of cesarean section is increased without clear clinical indications. WIDER IMPLICATIONS: Oocyte donation pregnancies are associated with a higher rate of placental disorders of pregnancy, such as gestational hypertension and pre-eclampsia. The risk of poorer neonatal outcomes is increased in oocyte donation pregnancies compared to other in-vitro fertilization pregnancies. Poorer outcomes have been demonstrated especially for twin pregnancies and in association with previous chronic pathologies or the development of obstetrics complications. PMID- 27271098 TI - Screening for obstructive sleep apnoea in cardiac rehabilitation: A position statement from the Australian Centre for Heart Health and the Australian Cardiovascular Health and Rehabilitation Association. AB - Obstructive sleep apnoea is highly prevalent in acute coronary syndrome patients eligible for enrolment in cardiac rehabilitation programmes. This condition is an independent predictor of increased morbidity and comorbid conditions in the general population and can lead to an increase in major adverse cardiac events such as revascularization, heart failure and hospital readmission in cardiac patients. There is convincing evidence that treatments such as continuous positive airway pressure or mandibular advancement devices can successfully treat obstructive sleep apnoea and these conditions can be improved or negated resulting in improved cardiac rehabilitation outcomes and improved health related quality of life. Given the potential benefits of obstructive sleep apnoea treatment it would make sense to screen for this condition upon entry to out patient cardiac rehabilitation programmes. A two-stage approach to screening is recommended, where patients are initially evaluated for the probability of having obstructive sleep apnoea using a brief questionnaire (The STOP-Bang) and then followed up with objective evaluation (portable home monitor or polysomnography) where necessary. Potential barriers to further referral and treatment could be partly mitigated by the training of cardiac rehabilitation staff in sleep disorders and screening. PMID- 27271100 TI - Paediatric and Perinatal Epidemiology: Changes in Leadership. PMID- 27271099 TI - Matrix Metalloproteinase-9 as a Marker for Plaque Rupture and a Predictor of Adverse Clinical Outcome in Patients with Acute Coronary Syndrome: An Optical Coherence Tomography Study. AB - OBJECTIVES: The present study sought to clarify the relationship between matrix metalloproteinase-9 (MMP-9) levels and plaque morphology demonstrated by optical coherence tomography (OCT), and to examine their prognostic impacts in patients with acute coronary syndrome (ACS). METHODS: MMP-9 levels were measured for patients with ACS (n = 249). Among 249 patients, 120 with evaluable OCT images were categorized into patients with ruptured plaques (n = 65) and those with nonruptured plaques (n = 55) on the basis of culprit lesion plaque morphology demonstrated by OCT. RESULTS: MMP-9 levels on admission were significantly higher in the rupture group than in the nonrupture group (p = 0.029). Although creatine kinase-MB (CK-MB) on admission was comparable between the groups, peak CK-MB was higher in the rupture group than in the nonrupture group (p < 0.001). By receiver operating characteristic curve analysis, the optimal cut-off value of MMP-9 to detect ruptured plaques was 65.5 ng/ml (p = 0.029). There was a nonstatistically significant trend toward increased cardiac death at 2 years (5.9 vs. 1.0%, p = 0.059) in patients with high MMP-9 (>=65.5 ng/ml) compared to those with low MMP 9 (<65.5 ng/ml). CONCLUSIONS: MMP-9 can differentiate ACS with ruptured plaques from nonruptured plaques, and MMP-9 may be a valuable predictor of long-term cardiac mortality in patients with ACS reflecting plaque rupture. PMID- 27271101 TI - Maternal and Neonatal Markers of the Homocysteine Pathway and Fetal Growth: The Generation R Study. AB - BACKGROUND: Suboptimal dietary intake during pregnancy may have long-term health implications in children. These effects may be mediated by fetal growth. We investigated the associations of early pregnancy and umbilical cord total homocysteine (tHcy), folate, and total and active vitamin B12 concentrations with fetal growth parameters repeatedly measured in pregnancy and at birth. METHODS: This study was performed in 5890 pregnant women, participating in a population based prospective cohort study. Blood samples were obtained from women in early pregnancy and from the umbilical vein at delivery. Fetal size parameters were repeatedly measured by ultrasound. Information about birth anthropometrics was retrieved from medical records. RESULTS: High early pregnancy maternal tHcy (>=8.31 MUmol/L), as compared with low maternal homocysteine (<=5.80 MUmol/L), and low early pregnancy maternal folate (<=9.10 nmol/L), as compared with high maternal folate (>=25.81 nmol/L) concentrations, were associated with reduced weight growth patterns throughout pregnancy, resulting in birthweight differences of -102.3 g (95% CI -139.6, -65.0) and -113.0 g (95% CI -159.6, -66.3), respectively. Low umbilical cord folate concentrations (<=15.20 nmol/L) as compared with high umbilical cord folate concentrations (>=28.41 nmol/L) were also associated with a lower birthweight and birth length (P < 0.001). Interestingly, compared with higher umbilical cord vitamin B12 , lower vitamin B12 concentrations were associated with a higher weight, length, and head circumference at birth (P < 0.01). CONCLUSION: Early pregnancy maternal and umbilical cord markers of the homocysteine pathway are significantly associated with fetal growth patterns. These differences arise from mid-pregnancy onwards. PMID- 27271103 TI - [Not Available]. PMID- 27271104 TI - [Not Available]. PMID- 27271102 TI - Can Bias Evaluation Provide Protection Against False-Negative Results in QT Studies Without a Positive Control Using Exposure-Response Analysis? AB - The revised ICH E14 document allows the use of exposure-response analysis to exclude a small QT effect of a drug. If plasma concentrations exceeding clinically relevant levels is achieved, a positive control is not required. In cases when this cannot be achieved, there may be a need for metrics to protect against false-negative results. The objectives of this study were to create bias in electrocardiogram laboratory QT-interval measurements and define a metric that can be used to detect bias severe enough to cause false-negative results using exposure-response analysis. Data from the IQ-CSRC study, which evaluated the QT effect of 5 QT-prolonging drugs, were used. Negative bias using 3 deterministic and 2 random methods was introduced into the reported QTc values and compared with fully automated data from the underlying electrocardiogram algorithm (COMPAS). The slope estimate of the Bland-Altman plot was used as a bias metric. With the deterministic bias methods, negative bias, measured between electrocardiogram laboratory values and COMPAS, had to be larger than approximately -20 milliseconds over a QTcF range of 100 milliseconds to cause failures to predict the QT effect of ondansetron, quinine, dolasetron, moxifloxacin, and dofetilide. With the random methods, the rate of false negatives was <=5% with bias severity < -10 milliseconds for all 5 drugs when plasma levels exceeded those of interest. Severe and therefore detectable bias has to be introduced into reported QTc values to cause false-negative predictions with exposure-response analysis. PMID- 27271105 TI - [Not Available]. PMID- 27271106 TI - Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity. AB - Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF kappaB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-kappaB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese. PMID- 27271107 TI - Enantioselective Collision-Activated Dissociation of Gas-Phase Tryptophan Induced by Chiral Recognition of Protonated L-Alanine Peptides. AB - Enantioselective dissociation in the gas phase is important for enantiomeric enrichment and chiral transmission processes in molecular clouds regarding the origin of homochirality in biomolecules. Enantioselective collision-activated dissociation (CAD) of tryptophan (Trp) and the chiral recognition ability of L alanine peptides (L-Ala n ; n = 2-4) were examined using a linear ion trap mass spectrometer. CAD spectra of gas-phase heterochiral H+(D-Trp)(L-Ala n ) and homochiral H+(L-Trp)(L-Ala n ) noncovalent complexes were obtained as a function of the peptide size n. The H2O-elimination product was observed in CAD spectra of both heterochiral and homochiral complexes for n = 2 and 4, and in homochiral H+(L-Trp)(L-Ala3), indicating that the proton is attached to the L-alanine peptide, and H2O loss occurs from H+(L-Ala n ) in the noncovalent complexes. H2O loss did not occur in heterochiral H+(D-Trp)(L-Ala3), where NH3 loss and (H2O + CO) loss were the primary dissociation pathways. In heterochiral H+(D-Trp)(L Ala3), the protonation site is the amino group of D-Trp, and NH3 loss and (H2O + CO) loss occur from H+(D-Trp). L-Ala peptides recognize D-Trp through protonation of the amino group for peptide size n = 3. NH3 loss and (H2O + CO) loss from H+(D Trp) proceeds via enantioselective CAD in gas-phase heterochiral H+(D-Trp)(L Ala3) at room temperature, whereas L-Trp dissociation was not observed in homochiral H+(L-Trp)(L-Ala3). These results suggest that enantioselective dissociation induced by chiral recognition of L-Ala peptides through protonation could play an important role in enantiomeric enrichment and chiral transmission processes of amino acids. PMID- 27271108 TI - Aquaporin 1 Is an Independent Marker of Poor Prognosis in Lung Adenocarcinoma. AB - BACKGROUND: Aquaporin 1 (AQP1) overexpression has been shown to be associated with uncontrolled cell replication, invasion, migration, and tumor metastasis. We aimed to evaluate AQP1 expression in lung adenocarcinomas and to examine its association with clinicopathological features and prognostic significance. We also investigated the association between AQP1 overexpression and epithelial mesenchymal transition (EMT) markers. METHODS: We examined AQP1 expression in 505 cases of surgically resected lung adenocarcinomas acquired at the Seoul National University Bundang Hospital from 2003 to 2012. Expression of AQP1 and EMT-related markers, including Ecadherin and vimentin, were analyzed by immunohistochemistry and tissue microarray. RESULTS: AQP1 overexpression was associated with several aggressive pathological parameters, including venous invasion, lymphatic invasion, and tumor recurrence. AQP1 overexpression tended to be associated with higher histological grade, advanced pathological stage, and anaplastic lymphoma kinase (ALK) translocation; however, these differences were not statistically significant. In addition, AQP1 overexpression positively correlated with loss of E-cadherin expression and acquired expression of vimentin. Lung adenocarcinoma patients with AQP1 overexpression showed shorter progression-free survival (PFS, 46.1 months vs. 56.2 months) compared to patients without AQP1 overexpression. Multivariate analysis confirmed that AQP1 overexpression was significantly associated with shorter PFS (hazard ratio, 1.429; 95% confidence interval, 1.033 to 1.977; p=.031). CONCLUSIONS: AQP1 overexpression was thereby concluded to be an independent factor of poor prognosis associated with shorter PFS in lung adenocarcinoma. These results suggested that AQP1 overexpression might be considered as a prognostic biomarker of lung adenocarcinoma. PMID- 27271109 TI - Detection of Tumor Multifocality Is Important for Prediction of Tumor Recurrence in Papillary Thyroid Microcarcinoma: A Retrospective Study and Meta-Analysis. AB - BACKGROUND: The clinicopathological characteristics and conclusive treatment modality for multifocal papillary thyroid microcarcinoma (mPTMC) have not been fully established. METHODS: A retrospective study, systematic review, and meta analysis were conducted to elucidate the clinicopathological significance of mPTMC. We investigated the multiplicity of 383 classical papillary thyroid microcarcinomas (PTMCs) and the clinicopathological significance of incidental mPTMCs. Correlation between tumor recurrence and multifocality in PTMCs was evaluated through a systematic review and meta-analysis. RESULTS: Tumor multifocality was identified in 103 of 383 PTMCs (26.9%). On linear regression analysis, primary tumor diameter was significantly correlated with tumor number (R(2)=0.014, p=.021) and supplemental tumor diameter (R(2)=0.117, p=.023). Of 103 mPTMCs, 61 (59.2%) were non-incidental, with tumor detected on preoperative ultrasonography, and 42 (40.8%) were diagnosed (incidental mPTMCs) on pathological examination. Lymph node metastasis and higher tumor stage were significantly correlated with tumor multifocality. However, there was no difference in nodal metastasis or tumor stage between incidental and non incidental mPTMCs. On meta-analysis, tumor multifocality was significantly correlated with tumor recurrence in PTMCs (odds ratio, 2.002; 95% confidence interval, 1.475 to 2.719, p<.001). CONCLUSIONS: Our results show that tumor multifocality in PTMC, regardless of manner of detection, is significantly correlated with aggressive tumor behavior. PMID- 27271110 TI - Heterotopic Ossification in the Gallbladder. PMID- 27271113 TI - Usability evaluation of the digital anger thermometer app. AB - The digital anger thermometer is a prototype for a mobile application (app) for use with adults in anger management treatment. The digital anger thermometer incorporates standards of software development in addition to anger management resources from the Substance Abuse and Mental Health Services Administration. The digital anger thermometer underwent a usability study conducted by five expert reviewers. The results indicate that it is easy to learn, efficient, and ergonomically sound. However, it does not offer support features or user-error tolerance. The digital anger thermometer prototype requires additional usability studies and comparative research in order for it to become an actual mental health app. PMID- 27271111 TI - Mammary-Type Myofibroblastoma: A Report of Two Cases. AB - Mammary-type myofibroblastoma (MFB) is a rare, benign spindle cell neoplasm occurring along the milkline, with extension from the mid-axilla to the medial groin. It is histologically and immunohistochemically identical to MFB of the breast and is part of a spectrum of lesions that includes spindle cell lipoma and cellular angiofibroma. Recently, we experienced two cases of mammary-type MFB involving male patients aged 30 and 58 years, respectively. The tumors were located in the right scrotal sac and in the right axilla. Wide excisions were performed. Microscopically, the masses were composed of haphazardly arranged, variably sized fascicles of bland spindle cells and were admixed with mature fat tissue. The spindle cells in both cases showed immunopositivity for desmin and CD34 and negativity for smooth muscle actin. Loss of retinoblastoma (RB)/13q14 loci is a characteristic genetic alteration of mammary-type MFB, and we identified loss of RB protein expression by immunohistochemical staining. We emphasize the importance of awareness of this rare neoplasm when a spindle cell neoplasm is accompanied by desmin immunopositivity. The second patient was alive without recurrence for 20 months, and the first patient had not been followed. PMID- 27271114 TI - Extracting and analyzing ejection fraction values from electronic echocardiography reports in a large health maintenance organization. AB - The left ventricular ejection fraction value is an important prognostic indicator of cardiovascular outcomes including morbidity and mortality and is often used clinically to indicate severity of heart disease. However, it is usually reported in free-text echocardiography reports. We developed and validated a computerized algorithm to extract ejection fraction values from echocardiography reports and applied the algorithm to a large volume of unstructured echocardiography reports between 1995 and 2011 in a large health maintenance organization. A total of 621,856 echocardiography reports with a description of ejection fraction values or systolic functions were identified, of which 70 percent contained numeric ejection fraction values and the rest (30%) were text descriptions explicitly indicating the systolic left ventricular function. The 12.1 percent (16.0% for male and 8.4% for female) of these extracted ejection fraction values are <45 percent. Validation conducted based on a random sample of 200 reports yielded 95.0 percent sensitivity and 96.9 percent positive predictive value. PMID- 27271115 TI - Genetic Diversity and Divergence in Populations of the Threatened Grassland Perennial Vincetoxicum atratum (Apocynaceae-Asclepiadoideae) in Japan. AB - We examined the genetic diversity and structure in populations of the endangered grassland herb Vincetoxicum atratum using 11 polymorphic microsatellite loci. Although the populations were small and disconnected, our molecular data indicated that the species maintains relatively high levels of genetic diversity and connectivity among populations. Population clustering analyses detected 2 to 3 clusters and most of the populations of V. atratum comprised admixture of these genetic clusters. These admixtures likely formed during the process of colonizing habitats that had been disturbed by human activities. However, STRUCTURE clustering detected low-admixtures in populations occurring in rocky maritime sites, which may not be suitable for agriculture/rangeland activities. High genetic diversity and population connectivity suggested that loss of the remaining populations by grassland reduction might be an immediate threat for this species. Small grasslands populations managed by local farmers need appropriate conservation practices. Although our results showed genetic diversity and gene flow among populations of V. atratum were high, it is possible that this resulted from the historical continuous distribution of the species. To examine this hypothesis, further periodical monitoring of the genetic diversity and the genetic differentiation for the species is needed for a conservation action of the species. PMID- 27271116 TI - Type, intensity and duration of daily physical activities performed by adults with spinal cord injury. AB - STUDY DESIGN: Secondary analysis of cross-sectional data. OBJECTIVES: To describe and compare (1) self-reported intensities and durations of specific types of daily physical activities and (2) minutes per day spent on daily physical activities across key demographic groups. SETTING: Community (Ontario, Canada). METHODS: Participants were 695 adults with spinal cord injury (SCI; 76% male, Mage=46.81+/-13.41 years, Myears post injury=15.19+/-11.10 years). Daily activities were assessed over the telephone using the Physical Activity Recall Assessment for People with SCI. Multivariate analyses of variance (MANOVA) were computed to test for differences in intensities and durations of different daily activities (objective 1) and between-group differences in minutes per day of daily activities (objective 2). RESULTS: Overall, participants reported 127.92+/ 142.79 min per day of daily physical activities with significantly more time spent in mild intensity (78.93+/-104.62 min per day) than moderate- (40.23+/ 68.71 min per day) or heavy-intensity activities (8.75+/-24.53 min per day). Four patterns emerged with respect to type, duration and intensity, with some activities being typically performed at lighter or heavier intensities than others. There were significant differences in minutes per day of activity intensity and duration between groups based on education, injury severity and mode of mobility (P<0.05). CONCLUSION: Given that some groups were more likely to engage in moderate-heavy-intensity activities, and some activities were more likely to be performed at moderate-heavy intensities, interventions that target key groups to increase certain daily activities may be one strategy to enhance overall physical activity participation among people with SCI. PMID- 27271117 TI - The differential effects of norepinephrine and dopamine on cerebrospinal fluid pressure and spinal cord perfusion pressure after acute human spinal cord injury. AB - STUDY DESIGN: Prospective vasopressor cross-over interventional studyObjectives:To examine how two vasopressors used in acute traumatic spinal cord injury (SCI) affect intrathecal cerebrospinal fluid pressure and the corresponding spinal cord perfusion pressure (SCPP). SETTING: Vancouver, British Columbia, Canada. METHODS: Acute SCI patients over the age of 17 with cervical or thoracic ASIA Impairment Scale (AIS). A, B or C injuries were enrolled in this study. Two vasopressors, norepinephrine and dopamine, were evaluated in a 'crossover procedure' to directly compare their effect on the intrathecal pressure (ITP). The vasopressor cross-over procedures were performed in the intensive care unit where ITP, mean arterial pressure (MAP) and heart rate were being continuously measured. The SCPP was calculated as the difference between MAP and ITP. RESULTS: A total of 11 patients were enrolled and included in our analysis. There were 6 patients with AIS A, 3 with AIS B and 2 with AIS C injuries at baseline. We performed 24 cross-over interventions in these 11 patients. There was no difference in MAP with the use of norepinephrine versus dopamine (84+/-1 mm Hg for both; P=0.33). Conversely, ITP was significantly lower with the use of norepinephrine than with dopamine (17+/-1 mm Hg vs 20+/-1 mm Hg, respectively, P<0.001). This decrease in ITP with norepinephrine resulted in an increased SCPP during the norepinephrine infusion when compared with dopamine (67+/-1 mm Hg vs 65+/-1 mm Hg respectively, P=0.0049). CONCLUSION: Norepinephrine was able to maintain MAP with a lower ITP and a correspondingly higher SCPP as compared with dopamine in this study. These results suggest that norepinephrine may be preferable to dopamine if vasopressor support is required post SCI to maintain elevated MAPs in accordance with published guidelines. PMID- 27271119 TI - Characterization of La1-xSrxMnO3 perovskite catalysts for hydrogen peroxide reduction. AB - We investigated the crystalline phase and electronic structure of perovskite-type La1-xSrxMnO3 (0.0 <= x <= 1.0) (LSMx) catalysts synthesized via the citric sol gel route, for H2O2 reduction. The resulting materials were characterized by XRD, XANES, TR-XANES, and TPO and, after calcination, consisted of cubic perovskite for 0.0 <= x <= 0.8 and hexagonal perovskite for x = 1.0. Mn species in the precalcined catalysts were oxidized to Mn(3+) for x = 0.0 to 0.6 and to Mn(2+) for x = 0.8 and 1.0. After calcination, Mn species were present in a mixed oxidation state of Mn(3+)/Mn(4+), while Sr(2+) and La(3+) were not altered. TR XANES and TPO showed that Mn species were oxidized at 210-220 degrees C and formed active perovskites LSM0.4 and LSM0.0 at 580 degrees C and 640 degrees C. This shows that Sr doping can reduce the oxidation temperature of LSMx with 0.2 <= x <= 0.4. However, the concentration of Mn(4+) in LSMx is increased which is useful for enhancing their catalytic activity and stability. When tested in an alkaline electrolyte, LSM0.6 containing the optimum Mn(4+)/Mn(3+) ratio promoted the formation of hydroxyl via the oxygen intercalation reaction and exhibited low polarization resistance and the highest catalytic activity for H2O2 reduction. PMID- 27271118 TI - Truncated Variants of Gaussia Luciferase with Tyrosine Linker for Site-Specific Bioconjugate Applications. AB - Gaussia luciferase (Gluc)-with its many favorable traits such as small size, bright emission, and exceptional stability-has become a prominent reporter protein for a wide range of bioluminescence-based detection applications. The ten internal cysteine residues crucial to functional structure formation, however, make expression of high quantities of soluble protein in bacterial systems difficult. In addition to this challenge, the current lack of structural data further complicates the use of Gluc for in vitro applications, such as biosensors, or cellular delivery, both of which rely heavily on robust and reproducible bioconjugation techniques. While Gluc is already appreciably small for a luciferase, a reduction in size that still retains significant bioluminescent activity, in conjunction with a more reproducible bioorthogonal method of chemical modification and facile expression in bacteria, would be very beneficial in biosensor design and cellular transport studies. We have developed truncated variants of Gluc, which maintain attractive bioluminescent features, and have characterized their spectral and kinetic properties. These variants were purified in high quantities from a bacterial system. Additionally, a C-terminal linker has been incorporated into these variants that can be used for reliable, specific modification through tyrosine-based bioconjugation techniques, which leave the sensitive network of cysteine residues undisturbed. PMID- 27271120 TI - Convergence Properties of Posttranslationally Modified Protein-Protein Switching Networks with Fast Decay Rates. AB - A significant conceptual difficulty in the use of switching systems to model regulatory networks is the presence of so-called "black walls," co-dimension 1 regions of phase space with a vector field pointing inward on both sides of the hyperplane. Black walls result from the existence of direct negative self regulation in the system. One biologically inspired way of removing black walls is the introduction of intermediate variables that mediate the negative self regulation. In this paper, we study such a perturbation. We replace a switching system with a higher-dimensional switching system with rapidly decaying intermediate proteins, and compare the dynamics between the two systems. We find that the while the individual solutions of the original system can be approximated for a finite time by solutions of a sufficiently close perturbed system, there are always solutions that are not well approximated for any fixed perturbation. We also study a particular example, where global basins of attraction of the perturbed system have a strikingly different form than those of the original system. We perform this analysis using techniques that are adapted to dealing with non-smooth systems. PMID- 27271121 TI - Mathematical Modeling of the Role of Survivin on Dedifferentiation and Radioresistance in Cancer. AB - We use a mathematical model to investigate cancer resistance to radiation, based on dedifferentiation of non-stem cancer cells into cancer stem cells. Experimental studies by Iwasa 2008, using human non-small cell lung cancer (NSCLC) cell lines in mice, have implicated the inhibitor of apoptosis protein survivin in cancer resistance to radiation. A marked increase in radio sensitivity was observed, after inhibiting survivin expression with a specific survivin inhibitor YM155 (sepantronium bromide). It was suggested that these observations are due to survivin-dependent dedifferentiation of non-stem cancer cells into cancer stem cells. Here, we confirm this hypothesis with a mathematical model, which we fit to Iwasa's data on NSCLC in mice. We investigate the timing of combination therapies of YM155 administration and radiation. We find an interesting dichotomy. Sometimes it is best to hit a cancer with a large radiation dose right at the beginning of the YM155 treatment, while in other cases, it appears advantageous to wait a few days until most cancer cells are sensitized and then radiate. The optimal strategy depends on the nature of the cancer and the dose of radiation administered. PMID- 27271123 TI - New computerized staging method to analyze mink testicular tissue in environmental research. AB - Histopathology of testicular tissue is considered to be the most sensitive tool to detect adverse effects on male reproduction. When assessing tissue damage, seminiferous epithelium needs to be classified into different stages to detect certain cell damages; but stage identification is a demanding task. The authors present a method to identify the 12 stages in mink testicular tissue. The staging system uses Gata-4 immunohistochemistry to visualize acrosome development and proved to be both intraobserver-reproducible and interobserver-reproducible with a substantial agreement of 83.6% (kappa = 0.81) and 70.5% (kappa = 0.67), respectively. To further advance and objectify this method, they present a computerized staging system that identifies these 12 stages. This program has an agreement of 52.8% (kappa 0.47) with the consensus staging by 2 investigators. The authors propose a pooling of the stages into 5 groups based on morphology, stage transition, and toxicologically important endpoints. The computerized program then reached a substantial agreement of 76.7% (kappa = 0.69). The computerized staging tool uses local ternary patterns to describe the texture of the tubules and a support vector machine classifier to learn which textures correspond to which stages. The results have the potential to modernize the tedious staging process required in toxicological evaluation of testicular tissue, especially if combined with whole-slide imaging and automated tubular segmentation. Environ Toxicol Chem 2017;36:156-164. (c) 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC. PMID- 27271122 TI - Asymptotic Analysis of a Target-Mediated Drug Disposition Model: Algorithmic and Traditional Approaches. AB - A detailed analysis is reported on a multiscale pharmacokinetic model, simulating the interaction of a drug with its target, the binding of the compounds and the outcome of their interaction. The analysis is based on the algorithmic computational singular perturbation (CSP) methodology. Among others, the analysis concludes that the partial equilibrium approximation and the quasi-steady-state approximation (PEA and QSSA) are valid in two distinct stages in the evolution of the process. Similar conclusions are reached from the algorithmic criteria for the validity of the QSSA and PEA. The reactions in the pharmacokinetic model that (i) generate the fast time scales, (ii) generate the constraints in which the system evolves and (iii) drive the system at various phases are identified, with the use of algorithmic CSP tools. These identifications are very important for the improvement of the model and for the identification of ways to control the evolution of the process. Regarding the qualitative understanding of the process, the present analysis systematises the findings in the literature and provides some new insights. PMID- 27271126 TI - Quality of Life: A Ubiquitous Phenomenon. PMID- 27271127 TI - Riptide. AB - In this article the author describes her experience of being diagnosed with breast cancer as a riptide experience. The ocean and many of its characteristics, such as the riptide, are used to describe the powering necessary to prevail during a cancer diagnosis and treatment. Five themes or currents within this riptide experience are identified: a shattered sense of well-being; feelings of anxiety, fear and uncertainty; learning to live one day at a time; the loving attention of family and friends; and,swimming with the turbulent sea. Concepts of powering uncovered in nursing research studies along with other theoretical concepts are presented to develop further these currents. PMID- 27271125 TI - The Interaction of Mitochondrial Biogenesis and Fission/Fusion Mediated by PGC 1alpha Regulates Rotenone-Induced Dopaminergic Neurotoxicity. AB - Parkinson's disease is a common neurodegenerative disease in the elderly, and mitochondrial defects underlie the pathogenesis of PD. Impairment of mitochondrial homeostasis results in reactive oxygen species formation, which in turn can potentiate the accumulation of dysfunctional mitochondria, forming a vicious cycle in the neuron. Mitochondrial fission/fusion and biogenesis play important roles in maintaining mitochondrial homeostasis. It has been reported that PGC-1alpha is a powerful transcription factor that is widely involved in the regulation of mitochondrial biogenesis, oxidative stress, and other processes. Therefore, we explored mitochondrial biogenesis, mitochondrial fission/fusion, and especially PGC-1alpha as the key point in the signaling mechanism of their interaction in rotenone-induced dopamine neurotoxicity. The results showed that mitochondrial number and mass were reduced significantly, accompanied by alterations in proteins known to regulate mitochondrial fission/fusion (MFN2, OPA1, Drp1, and Fis1) and mitochondrial biogenesis (PGC-1alpha and mtTFA). Further experiments proved that inhibition of mitochondrial fission or promotion of mitochondrial fusion has protective effects in rotenone-induced neurotoxicity and also promotes mitochondrial biogenesis. By establishing cell models of PGC 1alpha overexpression and reduced expression, we found that PGC-1alpha can regulate MFN2 and Drp1 protein expression and phosphorylation to influence mitochondrial fission/fusion. In summary, it can be concluded that PGC-1alpha mediated cross talk between mitochondrial biogenesis and fission/fusion contributes to rotenone-induced dopaminergic neurodegeneration. PMID- 27271128 TI - Power Relations: Their Embodiment in Research. AB - The purpose of this column is to consider the notion of power in research. To that end, the idea of power is considered from the perspective of philosophy and then linked to a nursing concept analysis that compares the differences between power over and power to. Then, the nature of power relations is compared and contrasted between quantitative and qualitative methodologies. PMID- 27271124 TI - Apolipoprotein D Overexpression Protects Against Kainate-Induced Neurotoxicity in Mice. AB - Excitotoxicity due to the excessive activation of glutamatergic receptors leads to neuronal dysfunction and death. Excitotoxicity has been implicated in the pathogenesis of a myriad of neurodegenerative diseases with distinct etiologies such as Alzheimer's and Parkinson's. Numerous studies link apolipoprotein D (apoD), a secreted glycoprotein highly expressed in the central nervous system (CNS), to maintain and protect neurons in various mouse models of acute stress and neurodegeneration. Here, we used a mouse model overexpressing human apoD in neurons (H-apoD Tg) to test the neuroprotective effects of apoD in the kainic acid (KA)-lesioned hippocampus. Our results show that apoD overexpression in H apoD Tg mice induces an increased resistance to KA-induced seizures, significantly attenuates inflammatory responses and confers protection against KA induced cell apoptosis in the hippocampus. The apoD-mediated protection against KA-induced toxicity is imputable in part to increased plasma membrane Ca2+ ATPase type 2 expression (1.7-fold), decreased N-methyl-D-aspartate receptor (NMDAR) subunit NR2B levels (30 %) and lipid metabolism alterations. Indeed, we demonstrate that apoD can attenuate intracellular cholesterol content in primary hippocampal neurons and in brain of H-apoD Tg mice. In addition, apoD can be internalised by neurons and this internalisation is accentuated in ageing and injury conditions. Our results provide additional mechanistic information on the apoD-mediated neuroprotection in neurodegenerative conditions. PMID- 27271129 TI - Ancient Ethical Practices of Dualism and Ethical Implications for Future Paradigms in Nursing. AB - Paradigms contain theoretical structures to guide scientific disciplines. Since ancient times, Cartesian dualism has been a prominent philosophy incorporated in the practice of medicine. The discipline of nursing has continued the body-mind emphasis with similar paradigmatic thinking and theories of nursing that separate body and mind. Future trends for paradigm and nursing theory development are harkening to former ways of thinking. In this article the author discusses the origins of Cartesian dualism and implications for its current usage. The author shall illuminate what it potentially means to engage in dualism in nursing and discuss possible ethical implications for future paradigm and theory development in nursing. PMID- 27271130 TI - Power's Presence in Nurse Education. AB - The notion of power has long been discussed in literature. There continues to exist a vast number of ideas as to what power really is and means. The author here discusses some early notions of power from the philosophical literature where there is debate as to whether power is innate or earned and bestowed upon persons. The potential for power as well as powers need for support from others is then examined in light of the nursing educational arena. Parse's humanbecoming school of thought also enlightens beliefs on power through the teaching-learning model as well as within the third principle of humanbecoming. These humanbecoming aspects are discussed regarding their presence or role in nursing academia. The column concludes with the notion that possibly the most important power possessed by all is the power to choose. PMID- 27271131 TI - Power in Practice: Moments of Reflection. AB - Power in practice reveals itself in many ways. There are many definitions of power but in nursing care it could be said that the power is within the patient. Nurses facilitate patients power by engaging them in dialogical engagements. This helps patients to decide how to utilize the power of living their quality. PMID- 27271132 TI - A Model for Peaceful Practice and Leadership. PMID- 27271133 TI - Dialogue on Peace and Power. AB - An analysis of how Peace and Power have evolved over time is described in this dialogue between Pamela Clarke and Peggy Chinn. PMID- 27271134 TI - Integrative Review on the Use of Newman Praxis Relationship in Chronic Illness. AB - Over the past 20 years, many Newman scholars across the globe have investigated health as expanding consciousness with persons living with chronic illness. This integrative review examines the use of the concept, relationship, and its seven dimensions-health, caring, consciousness, mutual process, patterning, presence, and meaning with persons with chronic illness when engaged in health as expanding consciousness praxis. A regular and sustained pattern of publication of studies that included the seven dimensions was found. Relationships among the dimensions of a Newman praxis relationship, chronic illness, and health as expanding consciousness are discussed. PMID- 27271135 TI - Healing and Transcendence: A Roy Adaptation Model-Guided Comparison. AB - Healing and transcendence are concepts of considerable interest to nurses who engage in holistic nursing practice. The two concepts are often used within the context of adaptation to describe the processes experienced by individuals who experience suffering and distress from various life events. Despite their intuitive significance to the human experience, the similarities and differences between the two concepts remains unclear. The purpose of this paper is to present the results of a Roy adaptation model-guided comparison of the two concepts that addresses their shared and distinct characteristics. PMID- 27271136 TI - Effects of a Meditation Program on Nurses' Power and Quality of Life. AB - This study evaluated the effects of meditation programs on nurses' power and quality of life. In this study, Barrett's power theory derived from Rogers' unitary human being science was used as a theoretical framework. A randomized controlled design with 50 recruited and randomly allocated participants was used. The results demonstrated that the eight-week meditation program significantly improved nurses' power and quality of life. These results suggest that meditation has positive effects on power and quality of life. PMID- 27271137 TI - Light in the Darkness. AB - The story of an El Salvadorian women made pregnant by a rape while immigrating to the United States is discussed from a humanbecoming paradigm perspective. Nursing practice from such a paradigm is seen as the opposite of such a violent crime and injustice, because it seeks to tenderly respect and provide for the dignity and freedom of all people. PMID- 27271138 TI - Penetrating the Fog: The Experience of Being Pregnant in Taiwan. AB - The purpose of this column is to explore the experience of being pregnant as talked about by women in Taiwan. In nursing and healthcare in general, there is a tendency to objectify the experience from a biomedical view, focusing on physiological changes and symptoms. A human science approach is here applied to help understand the themes that were evident in the comments of 23 pregnant Taiwanese women, about what being pregnant was like for them. The perspective used for the explanation was Parse's humanbecoming paradigm. Being pregnant is seen by the author as a chosen way of becoming visible-invisible becoming in the world which involves; being oneself, but not oneself, doubling up, and living with the mystery of the other. PMID- 27271139 TI - Epistemic Authority in Nursing Practice vs. Doctors' Orders. AB - The practice policy of doctors' orders is still deeply embedded in 21st century professional nurse practice, despite its profound incongruence with nursing's perspective, standards of practice, and advanced knowledge. The author in this article elaborates on the doctors' orders policy in relation to nursing's disciplinary perspective and epistemic authority in professional practice. PMID- 27271140 TI - The Two Nursing Disciplinary Scientific Revolutions: Florence Nightingale and Martha E. Rogers. AB - The purpose of this essay is to share Kan Koffi's ideas about scientific revolutions in the discipline of nursing. Koffi has proposed that the works of Florence Nightingale and Martha E. Rogers represent two scientific revolutions in nursing as a learned discipline. The outcome of these two scientific revolutions is a catalyst for critical disciplinary and paradigmatic debate about the universal conceptualization of nursing's distinctive professional and scientific knowledge. PMID- 27271141 TI - Are You Encouraging Nurses to Obtain a Doctorate? PMID- 27271144 TI - ANNUAL SPECIAL ISSUE "Biomechanical Engineering-Year in Review". PMID- 27271147 TI - Journal of Biomechanical Engineering: Legacy Paper 2016. PMID- 27271146 TI - 2015 Editors' Choice Papers. PMID- 27271148 TI - Society Awards 2015. PMID- 27271149 TI - 2015 Summer Biomechanics, Bioengineering, and Biotransport Conference Student Paper Competition. PMID- 27271151 TI - Portuguese Adaptation of a Faux Pas Test and a Theory of Mind Picture Stories Task. AB - BACKGROUND: Developmental concepts of 'Theory of Mind' (ToM) suggest that this cognitive domain is an innate human capacity requiring input from the social environment to mature. Research suggests substantial individual differences in ToM, depending on childhood experiences, genetics, and the presence or absence of a neuropsychiatric disorder. None of the existing ToM tests for adult populations have been made available in Portuguese. Accordingly, the main objective of this study was to evaluate the psychometric properties of the Portuguese versions of the Faux Pas (FP) Recognition Test and the ToM Picture Stories Task. SAMPLING AND METHODS: Both tests were given to a sample of 200 Portuguese adults (125 women and 75 men) aged between 18 and 60 years. RESULTS AND CONCLUSIONS: The psychometric analyses of the results indicate that the Portuguese version of the FP Recognition Test is appropriate for use in research and clinical settings, providing a composite score that reliably measures the ability to infer the thoughts and feelings of others in a 'faux pas' situation (Cronbach's alpha = 0.82). However, the ToM Picture Stories Task did not show acceptable psychometric qualities. PMID- 27271152 TI - ICT and Intellectual Disability: A Survey of Organizational Support at the Municipal Level in Sweden. AB - BACKGROUND: Young adults today have grown up in a society where information and communication technology (ICT) support empowerment and social participation. Young adults with mild-to-moderate intellectual disability are at risk for marginalization by the digital divide. The aim was to map and describe how municipal organizations in Sweden organize support in terms of policy and strategies to enable the use of ICT in social care for adults with a mild-to moderate intellectual disability. METHODS: A quantitative, cross-sectional survey including all municipalities in Sweden (n = 290) was conducted (response rate: 51%, n = 147). Descriptive statistics were used. RESULTS: Findings indicate a lack of organizational support for staff as well as for young adults with mild-to moderate intellectual disability. CONCLUSION: Municipalities request more knowledge about strategies for making ICT available. Despite the lack of comprehensive strategies for ICT, some Swedish municipalities have taken the initiative in this area. PMID- 27271153 TI - Breast Cancer Knowledge and Screening Practice and Barriers Among Women in Madinah, Saudi Arabia. AB - A breast screening program may help to reduce cancer mortality rates among women. However, the use of the screening program by women in Madinah city is low, and studies examining its practice and barriers of low uptake are sparse. To identify breast cancer knowledge, practice and screening barriers among women attending primary health centers (PHC) in Madinah, Saudi Arabia. A primary health center based cross-sectional study was performed in Madinah city in 2015. A multistage stratified cluster sample was obtained and included 465 women (15 years and older) from five PHC. Data concerning socio-demographics, knowledge about breast cancer, and practice and barriers of mammography use were collected using a structured questionnaire. The mean age of the studied 465 women was 34.9 +/- 12.2 years. Of these women, 27.7 and 38.5 % received mammography and performed breast self-examination, respectively. A high level of poor knowledge about breast cancer was detected in the overall studied women and those who never received a mammography, particularly knowledge related to the risk factors of breast cancer. The most important predictors of the barriers to mammography were incorrect beliefs about mammography and its procedures. A belief that mammography is painful was significantly associated with a 56 % reduction in its use (OR = 0.44; 95 % CI = 0.22-0.88). The high levels of poor knowledge about cancer breast observed in this study reflect the need for greater efforts to increase breast awareness education. PMID- 27271154 TI - [Spinal catheter-associated cerebrospinal fluid leak]. AB - Cerebrospinal fluid leak, with its typical postdural puncture headache, occurs in 8-25 % of patients after insertion of a spinal catheter for treatment with an intrathecal pain pump. Symptoms are usually self-limiting; only rarely is an epidural blood patch used. In this case of a 49-year-old woman, we assumed a postdural puncture headache after replacement of the spinal catheter. Because of the persistence of symptoms and serous wound secretion around the paravertebral incision, we decided to test the catheter under radiological control with a contrast agent. Leakage could be seen within the spinal catheter, which was responsible for the symptoms. Because of an ongoing infection accompanied by meningitis the whole system had to be removed. PMID- 27271155 TI - [Knowledge, attitude and opinion of patients regarding the new German legislation on advance care planning : Results of a survey in a department of general internal medicine]. AB - BACKGROUND: In September 2009 a new legislation for advance care planning was introduced in Germany with the important characteristics of bindingness and unlimited validity for individual directives. Knowledge regarding this act and the attitude towards its characteristics among patients is unclear. AIM OF THIS STUDY: Analysis of knowledge, attitude and opinion of patients in a general internal medical department regarding advance care planning in general and the recent German legislation. METHODS: A total of 200 consecutive patients in an internal medicine ward were interviewed with the help of a questionnaire regarding their attitude to and knowledge on advance care planning in general and the current legislation. RESULTS: Approximately 40 % of the patients had issued some form of directive (either advance care directive or health care proxy) and only 7.5 % were advised by their physicians to make an advance directive. Patients with no directive were not willing to deal with dying and death, were not well-informed about directives or assumed that relatives or physicians would make an appropriate decision. Characteristics of the new legislation were controversially assessed; only 21 % of the patients wished to have a literal implementation of their directive. Regarding the content of an advance directive, more than 80 % of the patients voted for pain control in the palliative setting. CONCLUSION: The proportion of patients with a directive regarding advance care planning is only slowly increasing. Many patients are not well-informed, do not want to deal with dying or would like to delegate decisions to relatives and physicians. The present characteristics of the German legislation are controversially assessed and often do not represent the wishes of the patients. PMID- 27271156 TI - [The Munster Charter : Implementation of high-quality pain therapy]. PMID- 27271157 TI - A Movement Monitor Based on Magneto-Inertial Sensors for Non-Ambulant Patients with Duchenne Muscular Dystrophy: A Pilot Study in Controlled Environment. AB - Measurement of muscle strength and activity of upper limbs of non-ambulant patients with neuromuscular diseases is a major challenge. ActiMyo(r) is an innovative device that uses magneto-inertial sensors to record angular velocities and linear accelerations that can be used over long periods of time in the home environment. The device was designed to insure long-term stability and good signal to noise ratio, even for very weak movements. In order to determine relevant and pertinent clinical variables with potential for use as outcome measures in clinical trials or to guide therapy decisions, we performed a pilot study in non-ambulant neuromuscular patients. We report here data from seven Duchenne Muscular Dystrophy (DMD) patients (mean age 18.5 +/- 5.5 years) collected in a clinical setting. Patients were assessed while wearing the device during performance of validated tasks (MoviPlate, Box and Block test and Minnesota test) and tasks mimicking daily living. The ActiMyo(r) sensors were placed on the wrists during all the tests. Software designed for use with the device computed several variables to qualify and quantify muscular activity in the non-ambulant subjects. Four variables representative of upper limb activity were studied: the rotation rate, the ratio of the vertical component in the overall acceleration, the hand elevation rate, and an estimate of the power of the upper limb. The correlations between clinical data and physical activity and the ActiMyo(r) movement parameters were analyzed. The mean of the rotation rate and mean of the elevation rate appeared promising since these variables had the best reliability scores and correlations with task scores. Parameters could be computed even in a patient with a Brooke functional score of 6. The variables chosen are good candidates as potential outcome measures in non-ambulant patients with Duchenne Muscular Dystrophy and use of the ActiMyo(r) is currently being explored in home environment. TRIAL REGISTRATION: ClinicalTrials.gov NCT01611597. PMID- 27271159 TI - Prognostic value of C-reactive protein in cirrhosis: external validation from the CANONIC cohort. AB - BACKGROUND/AIMS: The variations in C-reactive protein (CRP) levels have been reported to have prognostic significance in decompensated cirrhotic patients. We aimed to provide an external validation of a prognostic model combining model for end-stage liver disease (MELD) and 'sustained high CRP levels' as main variables and to optimize the model to the context of liver transplantation by focusing on 3-month mortality with no consideration of severe chronic extrahepatic diseases. PATIENTS AND METHODS: Data from cirrhotic patients enrolled in the CANONIC study were collected. Multivariate analyses used the competing risk model. The prognostic performance [area under receiver operating characteristic curve (AUROC)] of the model incorporating CRP variations within 15 days was compared with that of the MELD score alone. RESULTS: 583 decompensated cirrhotic patients with Child-Pugh more than B7 and serial CRP measures available were included. Of these, 111 patients had baseline CRP at least 29 mg/l and 60 still had CRP at least 29 mg/l at day 15+/-6 (group A). Multivariate analysis (competing risk) identified three predictors of 3-month mortality: high MELD score [hazard ratio (HR)=1.14; 95% confidence intervals (CI): 1.11-1.17, P<0.001], age (HR=1.04; 95% CI: 1.02-1.06, P<0.001), and group A (HR=1.69; 95% CI: 1.01-2.81, P=0.046). The performance of the three variables taken together for predicting 3-month mortality was 0.796 (AUROC), which was significantly higher than that of the MELD score (AUROC=0.769; P=0.019). CONCLUSION: In Child-Pugh higher than B7 cirrhotic patients with decompensation, prognostic models incorporating variations in CRP within 15 days and age predict 3-month mortality better than the MELD score alone. Such models would improve the ranking of candidates for liver transplantation by differentiating the severe patients with persistent systemic inflammation and intermediate MELD scores. PMID- 27271158 TI - An Algorithm to Identify Target-Selective Ligands - A Case Study of 5-HT7/5-HT1A Receptor Selectivity. AB - A computational procedure to search for selective ligands for structurally related protein targets was developed and verified for serotonergic 5-HT7/5-HT1A receptor ligands. Starting from a set of compounds with annotated activity at both targets (grouped into four classes according to their activity: selective toward each target, not-selective and not-selective but active) and with an additional set of decoys (prepared using DUD methodology), the SVM (Support Vector Machines) models were constructed using a selective subset as positive examples and four remaining classes as negative training examples. Based on these four component models, the consensus classifier was then constructed using a data fusion approach. The combination of two approaches of data representation (molecular fingerprints vs. structural interaction fingerprints), different training set sizes and selection of the best SVM component models for consensus model generation, were evaluated to determine the optimal settings for the developed algorithm. The results showed that consensus models with molecular fingerprints, a larger training set and the selection of component models based on MCC maximization provided the best predictive performance. PMID- 27271160 TI - The prevalence and co-occurrence of hematological complications at the time of diagnosis of chronic hepatitis C in Poland: a cross-sectional study. AB - OBJECTIVES: To evaluate the frequency, co-occurrence, and risk factors for hematological complications at the time of diagnosis of chronic hepatitis C (CHC). METHODS: This study included 1237 patients with CHC aged 18-88 years diagnosed in the years 1998-2010 in the Pomeranian region of Poland. Clinical data, cell blood count, liver biopsy, and biochemistry results were obtained retrospectively. RESULTS: Hematological complications were found in 31% of patients. The most frequent complication was thrombocytopenia (23.8%). The multivariate analysis showed a 5.1-fold increased risk (P<0.05) of at least one additional hematological complication in patients with thrombocytopenia. The greatest increase in risk (7.3) was related to leukopenia and cryoglobulinemia (2.3). The risk of leukopenia was correlated with the severity of thrombocytopenia. The risk of leukopenia and thrombocytopenia increased significantly from, respectively, stages 3 and 2 of liver fibrosis compared with patients without fibrosis. CONCLUSION: In patients with CHC, decreases in cell blood count occur quite frequently. The most often is mild and solitary thrombocytopenia, but if severe, it may be accompanied by leukopenia, especially in women. The presence of thrombocytopenia and leukopenia in patients with CHC may indicate advanced liver fibrosis or its final stage: cirrhosis. PMID- 27271162 TI - DFT-B3LYP study of interactions between host biphenyl-1-aza-18-crown-6 ether derivatives and guest Cd(2+): NBO, NEDA, and QTAIM analyses. AB - This report present the results of natural energy decomposition analysis (NEDA), natural bond orbital (NBO), and quantum theory of atoms in molecules (QTAIM) calculations of three derivatives of biphenyl-1-aza-18-crown-6 ether and their 1:1 complexes with Cd(2+). All calculations used the B3LYP density functional theory in combination with the 6-311G and WTBS basis sets for ligands and Cd(2+) ion, respectively. Ligands 1 and 3 have a single 1-aza-18-crown-6, substituent; ligand 2 has two such substituents. The results show that, in the optimized geometries of the complexes, the distance between N and Cd(2+) is greater than the distance between O and Cd(2+). NBO and QTAIM data confirm these results. There was no stabilization energy or bond critical point for N . . . Cd(2+) in NBO or QTAIM, respectively. Data show that the O . . . Cd(2+) interaction is a kind of closed shell interaction. The trend of the calculated stabilization energy was similar to the experimental data. Different contributions of interaction energies for complex formation were analyzed by NEDA, and the results show that the main component of the interactions is accounted for by polarization. PMID- 27271161 TI - Iron Overload or Oxidative Stress? Insight into a Mechanism of Early Cardiac Manifestations of Asymptomatic Hereditary Hemochromatosis Subjects with C282Y Homozygosity. AB - Hereditary hemochromatosis (HH) is a genetic disorder which affects the heart due to systemic iron overload and concomitant elevated oxidative stress. Increasing numbers of patients are diagnosed at an asymptomatic stage due to genetic testing. Subclinical abnormal left ventricular diastolic function (LVDF) and increased arrhythmias are noted in this population; however, the mechanism leading to these observances has not been well understood. In this study, we assessed the relationship between arrhythmia activity and biomarkers of oxidative stress and iron overload in order to elucidate the role of oxidative stress in this population since we observed a significant association with LVDF previously. A significant correlation between plasma malondialdehyde, a biomarker of oxidative stress, and supraventricular arrhythmia activity without a significant association with iron overload was identified (n = 22). Our findings further highlight a possible role of oxidative stress in early cardiac manifestations of HH. Further investigation is warranted to assess this role. PMID- 27271163 TI - Theoretical investigation of the addition reaction of the aluminum chlorosilylenoid H(2)SiAlCl(3) with ethylene. AB - The addition reaction of the aluminum chlorosilylenoid H2SiAlCl3 with ethylene was investigated using the M06-2X and QCISD methods for the first time. The calculated results demonstrate that the addition reaction proceeds via two pathways: path I involves just one transition state, while path II involves two transition states. Path I is more feasible dynamically, as it has a lower barrier height than path II. The effect of the solvent CH2Cl2 was taken into consideration using the PCM model. The results indicated that the addition reaction is less likely to occur in CH2Cl2 solvent than in vacuum. This work has therefore highlighted a new pathway for the synthesis of silicon heterocyclic compounds. Graphical Abstract Relative energies (in kJ.mol(-1)) of the stationary points along the potential energy surfaces of the addition reaction of H2SiAlCl3 with C2H4 (values in parentheses were calculated in CH2Cl2 solvent). PMID- 27271164 TI - Fumaric acid esters for psoriasis: a systematic review. AB - BACKGROUND: Psoriasis is a chronic skin disease associated with increased morbidity and mortality. Effective and safe long term treatment options are required to manage the illness successfully. A number of systemic agents are available, however, each of them has potentially significant side effects. Fumaric acid esters (FAE) are used first line in Germany for the management of moderate to severe psoriasis, however, their use in Ireland is on an unlicensed basis (Clinical and Experimental Dermatology 37:786-801, 2012). OBJECTIVES: The purpose of this literature review is to evaluate the efficacy and safety of FAEs in the management of moderate to severe psoriasis in adult patients. The reviewer intends to systematically review all available literature on the efficacy and/or safety of fumaric acid esters in the management of moderate to severe psoriasis in adult patients. METHODS: A systematic review of the literature was performed by one reviewer. The PubMed, TRIP, Embase, and Cochrane Collaboration databases were systematically interrogated to include randomised controlled trials, cohort studies and case studies evaluating the efficacy and/or safety of FAEs in the management of moderate to severe psoriasis in adult patients. Inclusion criteria were studies which included adults over 18 years of age, with a diagnosis of moderate to severe chronic plaque psoriasis, who were treated with FAEs and no other systemic anti-psoriatic agents concurrently. Exclusion criteria were studies involving children, mild psoriasis, studies which did not include patients with chronic plaque psoriasis, the use of FAE for the management of illnesses other than psoriasis, and patients treated with more than one systemic anti-psoriatic agent concurrently. RESULTS: In total 19 articles were selected for review including 2 randomised placebo controlled trials, 1 non-randomised comparative study, 7 retrospective cohort studies, 2 prospective cohort studies and 7 case studies. The findings suggest that FAEs are a safe and effective treatment option for the management of moderate to severe psoriasis in adult patients. Gastrointestinal side effects may occur on treatment initiation and may be minimised by slow dose titration. Lymphocytopenia and eosinophilia are common, however, they are rarely of significance and there is no high level of evidence available to suggest a resultant increased risk of infection or malignancy. Rarely alterations of renal and hepatic function may occur, however, these are largely reversible on treatment withdrawal. CONCLUSION: In conclusion, the use of FAE in the management of moderate to severe psoriasis is a promising treatment option, especially for those patients intolerant of, or unresponsive to other agents. If blood parameters are closely monitored during treatment as per the European Medicine Agencies guidelines (European Medicines Agency, 'Updated recommendations to minimise the risk of the rare brain infection PML with Tecfidera', http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2015/10/WC5001 6017.pdf , 2015) they may be safely used in practice. The licensing of FAEs in Ireland for the treatment of moderate to severe psoriasis would be desirable, increasing available treatment options. PMID- 27271166 TI - Correction: Signal Transduction at the Domain Interface of Prokaryotic Pentameric Ligand-Gated Ion Channels. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002393.]. PMID- 27271165 TI - The use of ultrasonography and digital mammography in women under 40 years with symptomatic breast cancer: a 7-year Irish experience. AB - BACKGROUND: Breast cancer in women under 40 years of age is rare and typically presents symptomatically. The optimal imaging modality for this patient group is controversial. Most women undergo ultrasonography with/without mammography. Young women typically have dense breasts, which can obscure the features of malignancy on film mammography, however, initial studies have suggested that digital mammography may have a more accurate diagnostic performance in younger women. Ultrasound generally performs well in this age group, although it is poor at detecting carcinoma in situ (DCIS). AIMS: To evaluate the comparative diagnostic performance of ultrasonography and digital mammography in the initial diagnostic evaluation of women under 40 years of age with symptomatic breast cancer. METHODS: Retrospective review of all women under the age of 40 years managed at our symptomatic breast cancer unit from January 2009 to December 2015. RESULTS: There were 120 patients that met the inclusion criteria for this study. The sensitivity of ultrasonography and digital mammography for breast cancer in this patient group was 95.8 and 87.5 %, respectively. The patients with a false negative mammographic examination were more likely to have dense breasts (p < 0.01). Five patients had a false negative ultrasonographic examination, withal of whom were diagnosed with DCIS detected by mammography. CONCLUSION: This study demonstrates the superior sensitivity of ultrasound for breast cancer in women under the age of 40 years, however, the results show that digital mammography has an important complimentary role in the comprehensive assessment of these patients, particularly in the diagnosis of DCIS. PMID- 27271176 TI - Impact on Life Expectancy of Withdrawing Thiopurines in Patients with Crohn's Disease in Sustained Clinical Remission: A Lifetime Risk-Benefit Analysis. AB - OBJECTIVE: Long-term treatment with thiopurines is associated with a decreased risk of Crohn's disease (CD) flare but an increased risk of various cancers depending on gender, age, and presence of extensive colitis. We evaluated risks and benefits of withdrawing thiopurines in patients with CD in prolonged remission. METHODS: We developed a Markov model assessing risks and benefits of withdrawing thiopurines compared to continuing thiopurines in a lifetime horizon. The model was stratified by age (35 and 65 years old at thiopurine withdrawal), gender and presence of extensive colitis. Parameter estimates were taken from French cohorts and hospital databases, cancer and death national registries and published literature. Life expectancy, rates of relapse, serious adverse events, and causes-of-death were evaluated. RESULTS: In patients without extensive colitis, continuing thiopurines increased life expectancy up to 0.03 years for 35 year-old men and women but decreased life expectancy down to 0.07 years for 65 year-old men and women. Withdrawal strategy became the preferred strategy at 40.6 years for men, and 45.7 years for women without extensive colitis. In patients with extensive colitis, continuation strategy was the preferred strategy regardless of age. Risk-benefit analysis was not modified by duration of CD activity. CONCLUSIONS: Factors determining life expectancy associated with withdrawal or continuation of thiopurines in patients with CD and in sustained clinical remission vary substantially according to gender, age and presence of extensive colitis. Individual decisions to continue or withdraw thiopurines in patients with CD in sustained remission should take into account these parameters. PMID- 27271178 TI - Regional inequalities in child malnutrition in Egypt, Jordan, and Yemen: a Blinder-Oaxaca decomposition analysis. AB - There is substantial evidence that on average, urban children have better health outcomes than rural children. This paper investigates the underlying factors that account for the regional disparities in child malnutrition in three Arab countries, namely; Egypt, Jordan, and Yemen. We use data on a nationally representative sample from the most recent rounds of the Demographic and Health Survey. A Blinder-Oaxaca decomposition analysis is conducted to decompose the rural-urban differences in child nutrition outcomes into two components; one that is explained by regional differences in the level of the determinants (covariate effects), and another component that is explained by differences in the effect of the determinants on the child nutritional status (coefficient effects). Results show that the under-five stunting rates are 20 % in Egypt, 46.5 % in Yemen, and 7.7 % in Jordan. The rural- urban gap in child malnutrition was minor in the case of Egypt (2.3 %) and Jordan (1.5 %), while the regional gap was significant in the case of Yemen (17.7 %). Results of the Blinder-Oaxaca decomposition show that the covariate effect is dominant in the case of Yemen while the coefficients effect dominates in the case of Jordan. Income inequality between urban and rural households explains most of the malnutrition gap. Results were robust to the different decomposition weighting schemes. By identifying the underlying factors behind the rural- urban health disparities, the findings of this paper help in designing effective intervention measures aimed at reducing regional inequalities and improving population health outcomes. PMID- 27271177 TI - Efficiency of Ontario primary care physicians across payment models: a stochastic frontier analysis. AB - OBJECTIVE: The study examines the relationship between the primary care model that a physician belongs to and the efficiency of the primary care physician in Ontario, Canada. METHODS: Survey data were collected from 183 self-selected physicians and linked to administrative databases to capture the provision of services to the patients served for the 12 month period ending June 30, 2013, and the characteristics of the patients at the beginning of the study period. Two stochastic frontier regression models were used to estimate efficiency scores and parameters for two separate outputs: the number of distinct patients seen and the number of visits. RESULTS: Because of missing data, only 165 physicians were included in the analyses. The average efficiency was 0.72 for both outputs with scores varying from 4 % to 93 % for the visits and 5 % to 94 % for the number of patients seen. We observed that there were both very low and very high efficiency scores within each model. These variations were larger than variations in average scores across models. PMID- 27271179 TI - Knowledge sharing behaviour and intensive care nurse innovation: the moderating role of control of care quality. AB - AIMS: This study investigates the influence of intensive care unit nurses' knowledge sharing behaviour on nurse innovation, given different conditions of care quality control. BACKGROUND: Health-care organisations face an increasing pressure to innovate while controlling care quality. We have little insight on how the control of care quality interacts with the knowledge sharing behaviour of intensive care nurses to affect their innovative behaviours. METHODS: We developed a multi-source survey study of more than 200 intensive care nurses at 22 intensive care units of 17 Danish hospitals. Two versions of the questionnaire were used - one designed for nurse employees and the other for the managing nurse(s). An ordinary least squares regression analysis was used to test the hypotheses. RESULTS: Different aspects of knowledge sharing affect innovation differently, depending on the strength of the control of care quality within the unit. CONCLUSIONS: The increasing pressures to implement the control of care quality and innovate may be conflicting, unless handled properly. IMPLICATIONS FOR NURSING MANAGEMENT: Process control at intensive care units should be loosened, when personal interaction between intensive care nurses is encouraged to stimulate nurse innovations. Alternatively, managers may develop a climate where helping others, especially with younger colleagues, offsets the negative effects of strong process control. PMID- 27271181 TI - Metformin Therapy and Circulating NT-proBNP Levels: The CAMERA Trial. PMID- 27271180 TI - Vitamin D Supplementation Reduces Intimal Hyperplasia and Restenosis following Coronary Intervention in Atherosclerotic Swine. AB - Vitamin D is a fat-soluble steroid hormone that activates vitamin D receptor to regulate multiple downstream signaling pathways and transcription of various target genes. There is an association between vitamin D deficiency and increased risk for cardiovascular disease. However, most of the studies are observational and associative in nature with limited data on clinical application. Thus, there is a need for more prospective randomized controlled studies to determine whether or not vitamin D supplementation provides cardiovascular protection. In this study, we examined the effects of the deficiency and supplementation of vitamin D on coronary restenosis following coronary intervention in atherosclerotic Yucatan microswine. Twelve Yucatan microswine were fed vitamin D-deficient (n = 4) or sufficient (n = 8) high cholesterol diet for 6-months followed by coronary intervention. Post-intervention, swine in the vitamin D-sufficient high cholesterol diet group received daily oral supplementation of either 1,000 IU (n = 4) or 3,000 IU (n = 4) vitamin D3. Six months later, optical coherence tomography (OCT) was performed to monitor the development of intimal hyperplasia and restenosis. Animals were euthanized to isolate arteries for histomorphometric and immunohistochemical studies. Animals had graded levels of serum 25(OH)D; vitamin D-deficient (15.33 +/- 1.45 ng/ml), vitamin D-sufficient + 1,000 IU oral vitamin D post-intervention (32.27 +/- 1.20 ng/ml), and vitamin D-sufficient + 3,000 IU oral vitamin D post-intervention (51.00 +/- 3.47 ng/ml). Findings from the OCT and histomorphometric studies showed a decrease in intimal hyperplasia and restenosis in vitamin D-supplemented compared to vitamin D-deficient swine. Vitamin D supplementation significantly decreased serum levels of TNF-alpha and IFN-gamma, upregulated serum levels of IL-10, and had no effect on serum IL-6 levels. These findings suggest that vitamin D supplementation limits neointimal formation following coronary intervention in atherosclerotic swine and provide the support for vitamin D supplementation to protect against the development of coronary restenosis. PMID- 27271182 TI - Day-and-Night Closed-Loop Control Using the Unified Safety System in Adolescents With Type 1 Diabetes at Camp. PMID- 27271183 TI - Antisense-Mediated Lowering of Plasma Apolipoprotein C-III by Volanesorsen Improves Dyslipidemia and Insulin Sensitivity in Type 2 Diabetes. AB - OBJECTIVE: To determine the effects of volanesorsen (ISIS 304801), a second generation 2'-O-methoxyethyl chimeric antisense inhibitor of apolipoprotein (apo)C-III, on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized, double-blind, placebo controlled trial was performed in 15 adult patients with type 2 diabetes (HbA1c >7.5% [58 mmol/mol]) and hypertriglyceridemia (TG >200 and <500 mg/dL). Patients were randomized 2:1 to receive volanesorsen 300 mg or placebo for a total of 15 subcutaneous weekly doses. Glucose handling and insulin sensitivity were measured before and after treatment using a two-step hyperinsulinemic-euglycemic clamp procedure. RESULTS: Treatment with volanesorsen significantly reduced plasma apoC III (-88%, P = 0.02) and TG (-69%, P = 0.02) levels and raised HDL cholesterol (HDL-C) (42%, P = 0.03) compared with placebo. These changes were accompanied by a 57% improvement in whole-body insulin sensitivity (P < 0.001). Importantly, we found a strong relationship between enhanced insulin sensitivity and both plasma apoC-III (r = -0.61, P = 0.03) and TG (r = -0.68, P = 0.01) suppression. Improved insulin sensitivity was sufficient to significantly lower glycated albumin ( 1.7%, P = 0.034) and fructosamine (-38.7 MUmol/L, P = 0.045) at the end of dosing and HbA1c (-0.44% [-4.9 mmol/mol], P = 0.025) 3 months postdosing. CONCLUSIONS: Volanesorsen reduced plasma apoC-III and TG while raising HDL-C levels. Importantly, glucose disposal, insulin sensitivity, and integrative markers of diabetes also improved in these patients after short-term treatment. PMID- 27271184 TI - CYP2C8 and SLCO1B1 Variants and Therapeutic Response to Thiazolidinediones in Patients With Type 2 Diabetes. AB - OBJECTIVE: Thiazolidinediones (TZDs) are putatively transported into the liver by OATP1B1 (encoded by SLCO1B1) and metabolized by CYP450 2C8 enzyme (encoded by CYP2C8). While CYP2C8*3 has been shown to alter TZD pharmacokinetics, it has not been shown to alter efficacy. RESEARCH DESIGN AND METHODS: We genotyped 833 Scottish patients with type 2 diabetes treated with pioglitazone or rosiglitazone and jointly investigated association of variants in these two genes with therapeutic outcome. RESULTS: The CYP2C8*3 variant was associated with reduced glycemic response to rosiglitazone (P = 0.01) and less weight gain (P = 0.02). The SLCO1B1 521T>C variant was associated with enhanced glycemic response to rosiglitazone (P = 0.04). The super responders defined by combined genotypes at CYP2C8 and SLCO1B1 had a 0.39% (4 mmol/mol) greater HbA1c reduction (P = 0.006) than the poor responders. Neither of the variants had a significant impact on pioglitazone response. CONCLUSIONS: These results show that variants in CYP2C8 and SLCO1B1 have a large clinical impact on the therapeutic response to rosiglitazone and highlight the importance of studying transporter and metabolizing genes together in pharmacogenetics. PMID- 27271185 TI - Role and Determinants of Adherence to Off-loading in Diabetic Foot Ulcer Healing: A Prospective Investigation. AB - OBJECTIVE: Studies indicate that off-loading adherence is low in patients with diabetic foot ulcers (DFUs), which may subsequently delay healing. However, there is little empirical evidence for this relationship or the factors that influence adherence. RESEARCH DESIGN AND METHODS: This prospective, multicenter, international study of 79 (46 from the U.K. and 33 the U.S.) persons with type 2 diabetes and plantar DFUs assessed the association between off-loading adherence and DFU healing over a 6-week period. Additionally, potential demographic, disease, and psychological determinants of adherence were examined. DFUs were off loaded with a removable device (77% a removable cast walker). Off-loading adherence was assessed objectively by activity monitors. Patient-reported measures included Hospital Anxiety and Depression Scale (HADS), Neuropathy and Foot Ulcer Quality of Life (NeuroQoL) instrument, and Revised Illness Perception Questionnaire (IPQ-R). RESULTS: Off-loading adherence was monitored for 35 +/- 10 days, and devices were used during 59 +/- 22% of subjects' activity. In multivariate analyses, smaller baseline DFU size, U.K. study site, and better off loading adherence predicted smaller DFU size at 6 weeks (P < 0.05). Better off loading adherence was, in turn, predicted by larger and more severe baseline DFUs, more severe neuropathy, and NeuroQoL foot pain (P < 0.05). In contrast, greater NeuroQoL postural instability predicted worse off-loading adherence (P < 0.001). HADS and IPQ-R measures were not significantly associated with off loading adherence. CONCLUSIONS: Off-loading adherence is associated with the amount of DFU healing that occurs, while postural instability is a powerful predictor of nonadherence. Clinicians should take this neuropathic symptom into consideration when selecting an off-loading device, as off-loading-induced postural instability may further contribute to nonadherence. PMID- 27271186 TI - Celiac Disease Negatively Influences Lipid Profiles in Young Children With Type 1 Diabetes: Effect of the Gluten-Free Diet. PMID- 27271187 TI - Does beta-Cell Autoimmunity Play a Role in Cystic Fibrosis-Related Diabetes? Analysis Based on the German/Austrian Diabetes Patienten Verlaufsdokumentation Registry. AB - OBJECTIVE: Research on beta-cell autoimmunity in cystic fibrosis (CF)-related diabetes (CFRD) is still rare. We aimed to analyze the frequency of beta-cell autoimmunity and the influence on age at diabetes onset, insulin requirement, type of insulin therapy, and hypoglycemic or ketoacidotic events in patients with CFRD compared with antibody-negative patients with CFRD in the Diabetes Patienten Verlaufsdokumentation (DPV) registry. RESEARCH DESIGN AND METHODS: We analyzed data of 837 patients with CFRD in the German/Austrian DPV database by multivariable mixed-regression modeling. RESULTS: In our cohort, 8.5% of patients with CFRD (n = 72) were found to be beta-cell antibody positive. There was a female preponderance in this patient group: 65.3 vs. 57.6%. Diabetes onset (median [interquartile range]) was earlier (14.00 [10.15-15.90] vs. 16.10 [13.50 21.20] years; P < 0.005), and insulin dose/kg body weight was higher (0.95 [0.61 1.15] vs. 0.67 [0.33-1.04] IU/kg; P < 0.05). There were also differences in the type of insulin treatment. Insulin pump therapy was used significantly more often in patients with CFRD with beta-cell autoimmunity (18.2 vs. 6.4%; P < 0.05). The differences for multiple daily injections (ICT) and conventional therapy (CT) were not significant (ICT: 67.7 vs. 79.0%; CT: 15.2 vs. 14.6). Oral antidiabetic agents were rarely used in both groups. Rate of severe hypoglycemia with coma and rate of ketoacidosis were higher in antibody-positive patients (hypoglycemia with coma: 8.0 vs. 1.4, P < 0.05; ketoacidosis: 9.3 vs. 0.9, P < 0.05). CONCLUSIONS: Presence of beta-cell autoantibodies in our cohort of patients with CFRD (8.5%) appeared to be greater than in the general population and was associated with female sex, earlier onset of diabetes, and higher insulin requirement. Insulin pump therapy was used significantly more often in patients with beta-cell antibodies. Severe hypoglycemia and ketoacidosis were significantly more frequent in CFRD with beta-cell autoimmunity compared with beta-cell antibody-negative patients with CFRD. PMID- 27271188 TI - Management of Diabetic Ketoacidosis in Severe Insulin Resistance. PMID- 27271189 TI - Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population With Monogenic Diabetes. AB - OBJECTIVE: Monogenic diabetes is rare but is an important diagnosis in pediatric diabetes clinics. These patients are often not identified as this relies on the recognition of key clinical features by an alert clinician. Biomarkers (islet autoantibodies and C-peptide) can assist in the exclusion of patients with type 1 diabetes and allow systematic testing that does not rely on clinical recognition. Our study aimed to establish the prevalence of monogenic diabetes in U.K. pediatric clinics using a systematic approach of biomarker screening and targeted genetic testing. RESEARCH DESIGN AND METHODS: We studied 808 patients (79.5% of the eligible population) <20 years of age with diabetes who were attending six pediatric clinics in South West England and Tayside, Scotland. Endogenous insulin production was measured using the urinary C-peptide creatinine ratio (UCPCR). C peptide-positive patients (UCPCR >=0.2 nmol/mmol) underwent islet autoantibody (GAD and IA2) testing, with patients who were autoantibody negative undergoing genetic testing for all 29 identified causes of monogenic diabetes. RESULTS: A total of 2.5% of patients (20 of 808 patients) (95% CI 1.6-3.9%) had monogenic diabetes (8 GCK, 5 HNF1A, 4 HNF4A, 1 HNF1B, 1 ABCC8, 1 INSR). The majority (17 of 20 patients) were managed without insulin treatment. A similar proportion of the population had type 2 diabetes (3.3%, 27 of 808 patients). CONCLUSIONS: This large systematic study confirms a prevalence of 2.5% of patients with monogenic diabetes who were <20 years of age in six U.K. clinics. This figure suggests that ~50% of the estimated 875 U.K. pediatric patients with monogenic diabetes have still not received a genetic diagnosis. This biomarker screening pathway is a practical approach that can be used to identify pediatric patients who are most appropriate for genetic testing. PMID- 27271190 TI - Association of Weight Loss Maintenance and Weight Regain on 4-Year Changes in CVD Risk Factors: the Action for Health in Diabetes (Look AHEAD) Clinical Trial. AB - OBJECTIVE: Short-term weight loss improves cardiovascular disease (CVD) risk factors. We sought to determine the longer-term effects of maintaining weight loss or, conversely, regaining weight. RESEARCH DESIGN AND METHODS: We used data from Action for Health in Diabetes (Look AHEAD), a randomized trial of intensive lifestyle intervention (ILI) compared to a control condition in overweight/obese individuals with type 2 diabetes. ILI participants were grouped according to weight change patterns, as follows: 1) no weight loss (+/-3% at years 1 and 4); 2) moderate weight loss (3-8% at years 1 and 4); 3) large weight loss (8-20% at years 1 and 4); 4) moderate loss/full regain (3-8% at year 1/+/-3% at year 4); 5) large loss/full regain (8-20% at year 1/+/- 3% year 4); and 6) large loss/partial regain (8-20% at year 1/3-8% at year 4) and changes in CVD risk factors were compared. RESULTS: Adjusting for baseline differences and medication use, larger weight losses produced greater improvements in HbA1c, systolic blood pressure, HDL cholesterol, and triglycerides at years 1 and 4 (all P <= 0.02). Despite maintenance of weight loss, HbA1c levels worsened between years 1 and 4, and remained below baseline only in those with large weight losses. We found no negative associations of losing and regaining weight relative to not having lost weight. Moreover, those who had large initial weight loss but full regain of weight had greater improvements in HbA1c levels at year 4 than those with smaller or no initial weight loss. CONCLUSIONS: Larger initial weight loss should be encouraged in individuals with type 2 diabetes, despite the possibility of regain. PMID- 27271191 TI - Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study). AB - OBJECTIVE: Exposure to maternal diabetes in utero may have a negative impact on the developing brain. The objective was to examine long-term cognitive consequences of intrauterine hyperglycemia in adolescent offspring of women with type 1 diabetes and to ascertain a possible association with maternal HbA1c. RESEARCH DESIGN AND METHODS: Offspring of a prospectively followed cohort of women with type 1 diabetes (n = 277) participated in a follow-up examination at the age of 13-19 years. A control group from the background population was identified (n = 301). Cognitive function was evaluated using Reynolds Intellectual Assessment Scales and classified into indices of composite intelligence, verbal and nonverbal intelligence, and composite memory. Frequencies of reading and writing problems and attendance to classes for children with learning difficulties were assessed. RESULTS: Offspring of women with type 1 diabetes scored lower in all normalized and standardized intelligence indices compared with controls: composite intelligence (95.7 vs. 100, P = 0.001), verbal intelligence (96.2 vs. 100, P = 0.004), nonverbal intelligence (96.4 vs. 100, P = 0.008), and composite memory (95.7 vs. 100, P = 0.001). A higher frequency of diabetes-exposed offspring had parent-reported learning difficulties in primary school. Differences between groups remained after adjustment for confounders and potential mediators. We found no direct association between maternal HbA1c and offspring cognitive function in the exposed group. CONCLUSIONS: Adolescent offspring of women with type 1 diabetes had lower cognitive function compared with a control group, also after adjustment for confounders and potential mediators. These differences may reflect direct harmful effects of maternal diabetes on neurodevelopment in the offspring. PMID- 27271193 TI - Further Conceptualizing Ethnic and Racial Identity Research: The Social Identity Approach and Its Dynamic Model. AB - This article proposes a further conceptualization of ethnic and racial identity (ERI) as a fundamental topic in developmental research. Adding to important recent efforts to conceptually integrate and synthesize this field, it is argued that ERI research will be enhanced by more fully considering the implications of the social identity approach. These implications include (a) the conceptualization of social identity, (b) the importance of identity motives, (c) systematic ways for theorizing and examining the critical role of situational and societal contexts, and (d) a dynamic model of the relation between ERI and context. These implications have not been fully considered in the developmental literature but offer important possibilities for moving the field forward in new directions. PMID- 27271192 TI - Long-term Microvascular Disease Outcomes in Patients With Type 2 Diabetes After Bariatric Surgery: Evidence for the Legacy Effect of Surgery. AB - OBJECTIVE: To identify and quantify any legacy effect of bariatric surgery on risk of incident microvascular disease in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective observational cohort study (n = 4,683; 40% racial/ethnic minority) of patients with type 2 diabetes who underwent bariatric surgery from 2001 through 2011. The primary outcome measure was incident microvascular disease defined as a composite indicator of the first occurrence of retinopathy, neuropathy, and/or nephropathy. The Cox proportional hazards framework was used to investigate the associations between type 2 diabetes remission/relapse status and time to microvascular disease. RESULTS: Covariate-adjusted analyses showed that patients who experienced type 2 diabetes remission had 29% lower risk of incident microvascular disease compared with patients who never remitted (hazard ratio [HR] 0.71 [95% CI 0.60, 0.85]). Among patients who experienced a relapse after remission, the length of time spent in remission was inversely related to the risk of incident microvascular disease; for every additional year of time spent in remission prior to relapse, the risk of microvascular disease was reduced by 19% (HR 0.81 [95% CI 0.67, 0.99]) compared with patients who never remitted. CONCLUSIONS: Our results indicate that remission of type 2 diabetes after bariatric surgery confers benefits for risk of incident microvascular disease even if patients eventually experience a relapse of their type 2 diabetes. This provides support for a legacy effect of bariatric surgery, where even a transient period of surgically induced type 2 diabetes remission is associated with lower long-term microvascular disease risk. PMID- 27271194 TI - Rapid Synthesis of Thin and Long Mo17O47 Nanowire-Arrays in an Oxygen Deficient Flame. AB - Mo17O47 nanowire-arrays are promising active materials and electrically conductive supports for batteries and other devices. While high surface area resulting from long, thin, densely packed nanowires generally leads to improved performance in a wide variety of applications, the Mo17O47 nanowire-arrays synthesized previously by electrically-heated chemical vapor deposition under vacuum conditions were relatively thick and short. Here, we demonstrate a method to grow significantly thinner and longer, densely packed, high-purity Mo17O47 nanowire-arrays with diameters of 20-60 nm and lengths of 4-6 MUm on metal foil substrates using rapid atmospheric flame vapor deposition without any chamber or walls. The atmospheric pressure and 1000 degrees C evaporation temperature resulted in smaller diameters, longer lengths and order-of-magnitude faster growth rate than previously demonstrated. As explained by kinetic and thermodynamic calculations, the selective synthesis of high-purity Mo17O47 nanowires is achieved due to low oxygen partial pressure in the flame products as a result of the high ratio of fuel to oxidizer supplied to the flame, which enables the correct ratio of MoO2 and MoO3 vapor concentrations for the growth of Mo17O47. This flame synthesis method is therefore a promising route for the growth of composition-controlled one-dimensional metal oxide nanomaterials for many applications. PMID- 27271195 TI - Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a Phase 3 study. AB - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. Psoriasis impacts on physical and psychological well being; improvements in health-related quality of life (HRQoL) with etanercept in psoriasis are well documented. OBJECTIVE: To evaluate HRQoL with tofacitinib, vs. placebo or etanercept, in the Phase 3, randomized, placebo-controlled, non inferiority, Oral-treatment Psoriasis Trial (OPT) Compare Study (NCT01241591). METHODS: Adults with moderate to severe chronic plaque psoriasis were randomized 3:3:3:1 to tofacitinib 10 or 5 mg twice daily (BID), etanercept 50 mg twice weekly or placebo, for 12 weeks. Patient-reported outcomes (PROs) included Dermatology Life Quality Index (DLQI), Itch Severity Item and Patient Global Assessment of psoriasis. RESULTS: At baseline, 83.4% (911/1092) of patients had a DLQI score ranging between 6 and 30, indicating a substantial burden of disease. By Week 12, 47.3%, 43.6% and 30.9% of patients in the tofacitinib 10 mg BID, etanercept and tofacitinib 5 mg BID groups, respectively, had a DLQI score of 0 or 1 (no effect of psoriasis on QoL) vs. 7.8% for placebo (all P < 0.0001). Tofacitinib significantly reduced itch vs. placebo (P < 0.05 both doses) and etanercept (P < 0.0001 both doses) within 1 day of starting treatment. Furthermore, reductions in itch were greater with tofacitinib 10 mg BID, vs. etanercept, at Weeks 2-12 (all time points P < 0.05). At Week 2, an Itch Severity Item score of 'little or no itch' was more frequent with tofacitinib 10 mg (68.6%) vs. etanercept (57.4%) and placebo (12.2%), and the PtGA response rate was significantly greater with tofacitinib 10 mg vs. placebo (P < 0.05). CONCLUSION: Oral tofacitinib provided significant improvements across multiple PROs by Week 12. Improvements with tofacitinib 10 mg BID were comparable to etanercept, and improvements in itch were greater and more rapid with tofacitinib 10 mg BID. PMID- 27271196 TI - An E3-ligase-based method for ablating inhibitory synapses. AB - Although neuronal activity can be modulated using a variety of techniques, there are currently few methods for controlling neuronal connectivity. We introduce a tool (GFE3) that mediates the fast, specific and reversible elimination of inhibitory synaptic inputs onto genetically determined neurons. GFE3 is a fusion between an E3 ligase, which mediates the ubiquitination and rapid degradation of proteins, and a recombinant, antibody-like protein (FingR) that binds to gephyrin. Expression of GFE3 leads to a strong and specific reduction of gephyrin in culture or in vivo and to a substantial decrease in phasic inhibition onto cells that express GFE3. By temporarily expressing GFE3 we showed that inhibitory synapses regrow following ablation. Thus, we have created a simple, reversible method for modulating inhibitory synaptic input onto genetically determined cells. PMID- 27271197 TI - Quantitative detection of low-abundance somatic structural variants in normal cells by high-throughput sequencing. AB - The detection and quantification of low-abundance somatic DNA mutations by high throughput sequencing is challenging because of the difficulty of distinguishing errors from true mutations. There are several approaches available for analyzing somatic point mutations and small insertions or deletions, but an accurate genome wide assessment of somatic structural variants (somSVs) in bulk DNA is still not possible. Here we present Structural Variant Search (SVS), a method to accurately detect rare somSVs by low-coverage sequencing. We demonstrate direct quantitative assessment of elevated somSV frequencies induced by known clastogenic compounds in human primary cells. PMID- 27271199 TI - Usability evaluation of low-cost virtual reality hand and arm rehabilitation games. AB - The emergence of lower-cost motion tracking devices enables home-based virtual reality rehabilitation activities and increased accessibility to patients. Currently, little documentation on patients' expectations for virtual reality rehabilitation is available. This study surveyed 10 people with stroke for their expectations of virtual reality rehabilitation games. This study also evaluated the usability of three lower-cost virtual reality rehabilitation games using a survey and House of Quality analysis. The games (kitchen, archery, and puzzle) were developed in the laboratory to encourage coordinated finger and arm movements. Lower-cost motion tracking devices, the P5 Glove and Microsoft Kinect, were used to record the movements. People with stroke were found to desire motivating and easy-to-use games with clinical insights and encouragement from therapists. The House of Quality analysis revealed that the games should be improved by obtaining evidence for clinical effectiveness, including clinical feedback regarding improving functional abilities, adapting the games to the user's changing functional ability, and improving usability of the motion tracking devices. This study reports the expectations of people with stroke for rehabilitation games and usability analysis that can help guide development of future games. PMID- 27271198 TI - Dense transcript profiling in single cells by image correlation decoding. AB - Sequential barcoded fluorescent in situ hybridization (seqFISH) allows large numbers of molecular species to be accurately detected in single cells, but multiplexing is limited by the density of barcoded objects. We present correlation FISH (corrFISH), a method to resolve dense temporal barcodes in sequential hybridization experiments. Using corrFISH, we quantified highly expressed ribosomal protein genes in single cultured cells and mouse thymus sections, revealing cell-type-specific gene expression. PMID- 27271200 TI - International prescribing practices in obsessive-compulsive disorder (OCD). AB - OBJECTIVES: To assess rates of psychotropic medication use in patients with obsessive-compulsive disorder (OCD) in seven different countries on five continents and to compare these with international treatment guidelines. METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their patients with OCD and on their incidence of psychotropic use. Consistency of summary statistics across countries was evaluated. RESULTS: The data came from Brazil (n = 955), Italy (n = 750), South Africa (n = 555), Japan (n = 382), Australia (n = 213), India (n = 202) and Spain (n = 82). The majority (77.9%; n = 2445) of the total sample of 3139 participants received a psychotropic medication. Consistent with international guidelines, selective serotonin reuptake inhibitors (SSRIs) were most commonly used (73.5%, n = 1796), but their use ranged from 59% in Australia to 96% in Japan. Clomipramine use varied from 5% in Japan and South Africa to 26% in India and Italy. Atypical antipsychotic use ranged from 12% in South Africa to 50% in Japan. CONCLUSIONS: Pharmacotherapy for OCD varied significantly across sites. Prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that may play a role in the variation in prescribing practices internationally and whether these variations influence treatment outcomes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271202 TI - Non-classical Helices with cis Carbon-Carbon Double Bonds in the Backbone: Structural Features of alpha,gamma-Hybrid Peptide Foldamers. AB - The impact of geometrically constrained cis alpha,beta-unsaturated gamma-amino acids on the folding of alpha,gamma-hybrid peptides was investigated. Structure analysis in single crystals and in solution revealed that the cis carbon-carbon double bonds can be accommodated into the 12-helix without deviation from the overall helical conformation. The helical structures are stabilized by 4->1 hydrogen bonding in a similar manner to the 12-helices of beta-peptides and the 310 helices of alpha-peptides. These results show that functional cis carbon carbon double bonds can be accommodated into the backbone of helical peptides. PMID- 27271203 TI - Anisotropic thermal transport in Weyl semimetal TaAs: a first principles calculation. AB - A fundamental understanding of the phonon transport property is crucial to predict the thermal management performance in micro/nano-electronic devices. By combining first principle calculations and Boltzmann phonon transport equation, we investigate thermal transport in TaAs-a typical Weyl semimetal. The lattice thermal conductivity of TaAs at room temperature was found to be 39.26 W mK(-1) and 24.78 W mK(-1) along the a(b) and c crystal axis, respectively, showing obvious anisotropy. Detailed analyses of the mode level phonon properties further revealed that the three acoustic phonon modes dominate the overall thermal transport and the major phonon scattering channels in this typical Weyl semimetal were TA1/TA2/LA + O <-> O and A + A <-> O. The representative phonon mean free path of TaAs was also calculated in this paper, which provide helpful guidance for the thermal management of TaAs-based electronic devices. PMID- 27271201 TI - Prolonged esophageal acid exposures induce synaptic downscaling of cortical membrane AMPA receptor subunits in rats. AB - BACKGROUND: We recently reported the involvement of AMPA (alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid) receptor subunit upregulation and phosphorylation in the rostral cingulate cortex (rCC) as the underlying mechanism of acute esophageal acid-induced cortical sensitization. Based on these findings, we proposed to investigate whether prolonged esophageal acid exposures in rats exhibit homeostatic synaptic scaling through downregulation of AMPA receptor expression in rCC neurons. We intended to study further whether this compensatory mechanism is impaired when rats are pre-exposed to repeated esophageal acid exposures neonatally during neuronal development. METHODS: Two different esophageal acid exposure protocols in rats were used. Since AMPA receptor trafficking and channel conductance depend on CaMKIIalpha-mediated phosphorylation of AMPA receptor subunits, we examined the effect of esophageal acid on CaMKIIalpha activation and AMPA receptor expression in synaptoneurosomes and membrane preparations from rCCs. KEY RESULTS: In cortical membrane preparations, GluA1 and pGluA1Ser(831) expression were significantly downregulated following prolonged acid exposures in adult rats; this was accompanied by the significant downregulation of cortical membrane pCaMKIIalpha expression. No change in GluA1 and pGluA1Ser(831) expression was observed in rCC membrane preparations in rats pre-exposed to acid neonatally followed by adult rechallenge. CONCLUSIONS & INFERENCES: This study along with our previous findings suggests that synaptic AMPA receptor subunits expression and phosphorylation may be involved bidirectionally in both esophageal acid-induced neuronal sensitization and acid-dependent homeostatic plasticity in cortical neurons. The impairment of homeostatic compensatory mechanism as observed following early-in-life acid exposure could be the underlying mechanism of heightening cortical sensitization and esophageal hypersensitivity in patients with gastroesophageal reflux disease. PMID- 27271204 TI - Hiding effort to gain a competitive advantage: Evidence from China. AB - : Previous studies with Western populations have shown that adolescents' tendency to downplay their academic effort is affected by two kinds of motives: ability related motives (e.g., to appear competent) and social approval motives (e.g., to be popular). In this research, we test for the presence of additional competition related motives in China, a culture placing strong emphasis on academic competition. Study 1 (N = 150) showed that, in response to a scenario in which a hard-working high-school junior hid effort from classmates, the most highly endorsed explanation was "to influence others to work less hard to maintain a competitive advantage." Study 2 (N = 174) revealed that competition-related explanations were endorsed relatively more often when the speaker and audience had similar academic rankings. This tendency was most evident when both speaker and audience were top performers, and when this was the case, participants' desire to demonstrate superiority over others was a positive predictor of endorsement of competition-related motives. Study 3 (N = 137) verified that competition-related motives were more strongly endorsed among Chinese participants than U.S. PARTICIPANTS: These results suggest that at least in cultures that emphasize academic competition and in contexts where competition is salient, hiding effort is often about attempting to gain strategic advantage. PMID- 27271205 TI - Second bioluminescence-activating component in the luminous fungus Mycena chlorophos. AB - Mycena chlorophos is an oxygen-dependent bioluminescent fungus. The mechanisms underlying its light emission are unknown. A component that increased the bioluminescence intensity of the immature living gills of M. chlorophos was isolated from mature M. chlorophos gills and chemically characterized. The bioluminescence-activating component was found to be trans-3,4-dihydroxycinnamic acid and its bioluminescence activation was highly structure-specific. 13 C- and 18 O-labelling studies using the immature living gills showed that trans-3,4 dihydroxycinnamic acid was synthesized from trans-4-hydroxycinnamic acid in the gills by hydroxylation with molecular oxygen as well as by the general metabolism, and trans-3,4-dihydroxycinnamic acid did not produce hispidin (detection-limit concentration: 10 pmol/1 g wet gill). Addition of 0.01 mM hispidin to the immature living gills generated no bioluminescence activation. These results suggested that the prompt bioluminescence activation resulting from addition of trans-3,4-dihydroxycinnamic acid could not be attributed to the generation of hispidin. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271207 TI - Networks of plants: how to measure similarity in vegetable species. AB - Despite the common misconception of nearly static organisms, plants do interact continuously with the environment and with each other. It is fair to assume that during their evolution they developed particular features to overcome similar problems and to exploit possibilities from environment. In this paper we introduce various quantitative measures based on recent advancements in complex network theory that allow to measure the effective similarities of various species. By using this approach on the similarity in fruit-typology ecological traits we obtain a clear plant classification in a way similar to traditional taxonomic classification. This result is not trivial, since a similar analysis done on the basis of diaspore morphological properties do not provide any clear parameter to classify plants species. Complex network theory can then be used in order to determine which feature amongst many can be used to distinguish scope and possibly evolution of plants. Future uses of this approach range from functional classification to quantitative determination of plant communities in nature. PMID- 27271208 TI - Accessible bioprinting: adaptation of a low-cost 3D-printer for precise cell placement and stem cell differentiation. AB - The precision and repeatability offered by computer-aided design and computer numerically controlled techniques in biofabrication processes is quickly becoming an industry standard. However, many hurdles still exist before these techniques can be used in research laboratories for cellular and molecular biology applications. Extrusion-based bioprinting systems have been characterized by high development costs, injector clogging, difficulty achieving small cell number deposits, decreased cell viability, and altered cell function post-printing. To circumvent the high-price barrier to entry of conventional bioprinters, we designed and 3D printed components for the adaptation of an inexpensive 'off-the shelf' commercially available 3D printer. We also demonstrate via goal based computer simulations that the needle geometries of conventional commercially standardized, 'luer-lock' syringe-needle systems cause many of the issues plaguing conventional bioprinters. To address these performance limitations we optimized flow within several microneedle geometries, which revealed a short tapered injector design with minimal cylindrical needle length was ideal to minimize cell strain and accretion. We then experimentally quantified these geometries using pulled glass microcapillary pipettes and our modified, low-cost 3D printer. This systems performance validated our models exhibiting: reduced clogging, single cell print resolution, and maintenance of cell viability without the use of a sacrificial vehicle. Using this system we show the successful printing of human induced pluripotent stem cells (hiPSCs) into Geltrex and note their retention of a pluripotent state 7 d post printing. We also show embryoid body differentiation of hiPSC by injection into differentiation conducive environments, wherein we observed continuous growth, emergence of various evaginations, and post-printing gene expression indicative of the presence of all three germ layers. These data demonstrate an accessible open-source 3D bioprinter capable of serving the needs of any laboratory interested in 3D cellular interactions and tissue engineering. PMID- 27271209 TI - An Insight into a Blockbuster Phytomedicine; Marrubium vulgare L. Herb. More of a Myth than a Reality? AB - Aerial parts and the root of Marrubium vulgare L. (white horehound) have been traditionally used in Europe and in southern and eastern Mediterranean countries. During colonization, the plant was introduced in America to great levels of popularity because of the simplicity of its growing; it was especially popular in Mexico and Brazil, where it has been known as 'maromba', 'marroio' or 'marroio branco'. Ethnopharmacological uses of M. vulgare include treating respiratory diseases such as acute or chronic bronchitis, colds and asthma. The plant is also used in cases where there is a lack of appetite or dyspepsia and for diagnosed type II diabetes. It has even been used for antihypertensive therapy. For decades, scientists have carried out extensive research trying to explain these and other pharmacologic actions. It is time to systematize and critically analyse the quality of results found to date. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271210 TI - Collagen-like antimicrobial peptides. AB - Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016. PMID- 27271211 TI - Pain hypersensitivity in congenital blindness is associated with faster central processing of C-fibre input. AB - BACKGROUND: We have recently shown that visual deprivation from birth exacerbates responses to painful thermal stimuli. However, the mechanisms underlying pain hypersensitivity in congenital blindness are unclear. METHODS: To study the contribution of Adelta- and C-fibres in pain perception, we measured thresholds and response times to selective C- and Adelta-fibre activation in congenitally blind, late blind and normally sighted participants. Ultrafast constant temperature heat pulses were delivered to the hand with a CO2 laser using an interleaved adaptive double staircase procedure. Participants were instructed to respond as quickly as possible when detecting a laser-induced sensation. We used a 650 ms cut-off criterion to distinguish fast Adelta- from slow C-fibre-mediated sensations. RESULTS: Congenitally blind participants showed significantly faster reaction times to C- but not to Adelta-fibre-mediated sensations. In contrast, thresholds for Adelta- and C-fibre stimulation did not differ between groups. Late blind individuals did not differ from sighted controls in any aspect. A follow-up experiment using only suprathreshold stimuli for Adelta- and C-fibre activation confirmed these findings and further showed that congenitally blind individuals detected significantly more C-fibre-mediated stimuli than sighted controls. A decomposition analysis of the reaction times indicated that the faster response times in the congenitally blind are due to more efficient central processing of C-fibre-mediated sensations. CONCLUSION: The increased sensitivity to painful thermal stimulation in congenital blindness may be due to more efficient central processing of C-fibre-mediated input, which may help to avoid impending dangerous encounters with stimuli that threaten the bodily integrity. WHAT DOES THIS STUDY ADD?: Hypersensitivity to heat pain in congenital blindness is associated with faster responses to C-fibre activation, likely caused by more efficient central processing of C-fibre-mediated input. PMID- 27271212 TI - Cell death triggering and effector recognition by Sw-5 SD-CNL proteins from resistant and susceptible tomato isolines to Tomato spotted wilt virus. AB - Only a limited number of dominant resistance genes acting against plant viruses have been cloned, and further functional studies of these have been almost entirely limited to the resistance genes Rx against Potato virus X (PVX) and N against Tobacco mosaic virus (TMV). Recently, the cell-to-cell movement protein (NSM ) of Tomato spotted wilt virus (TSWV) has been identified as the avirulence determinant (Avr) of Sw-5b-mediated resistance, a dominant resistance gene which belongs to the class of SD-CC-NB-LRR (Solanaceae domain-coiled coil-nucleotide binding-leucine-rich repeat, SD-CNL) resistance genes. On transient expression of the NSM protein in tomato and transgenic Nicotiana benthamiana harbouring the Sw 5b gene, a hypersensitive cell death response (HR) is triggered. Here, it is shown that high accumulation of the Sw-5b protein in N. benthamiana leaves, achieved by co-expression of the Sw-5b protein with RNA silencing suppressors (RSSs), leads to auto-activity in the absence of NSM . In a similar approach, Sw 5a, the highest conserved paralogue of Sw-5b from Solanum peruvianum, also triggered HR by auto-activation, whereas the highest conserved orthologue from susceptible S. lycopersicum, named Sw-5aS , did not. However, neither of the last two homologues was able to trigger an NSM -dependent HR. Truncated and mutated versions of these Sw-5 proteins revealed that the NB-ARC [nucleotide-binding adaptor shared by Apaf-1 (from humans), R proteins and CED-4 (from nematodes)] domain is sufficient for the triggering of HR and seems to be suppressed by the SD-CC domain. Furthermore, a single mutation was sufficient to restore auto activity within the NB-ARC domain of Sw-5aS . When the latter domain was fused to the Sw-5b LRR domain, NSM -dependent HR triggering was regained, but not in the presence of its own Sw-5aS LRR domain. Expression analysis in planta revealed a nucleocytoplasmic localization pattern of Sw-5b, in which the SD-CC domain seems to be required for nuclear translocation. Although the Sw-5 N-terminal CC domain, in contrast with Rx, contains an additional SD, most findings from this study support a conserved role of domains within NB-LRR (NLR) proteins against plant viruses. PMID- 27271213 TI - Predictors of psychological distress in advanced cancer patients under palliative treatments. AB - This work aims to investigate the factors associated with psychological distress in advanced cancer patients under palliative treatment. We comprehensively assessed the demographic, psychosocial and health factors of 158 advanced cancer patients. Patients with high and low distress, according to the Hospital Anxiety and Depression Scale, were compared. A regression analysis was built to identify the best predictors of distress. Patients with high psychological distress (81%) were more likely to have lung cancer, suicidal ideation, hopelessness, low quality of life and poor body image than those without. In the multivariate model, only poor emotional functioning (OR = .89; 95% CI = .83-.95; p <= .001), hopelessness (OR = .86; 95% CI = .78-.94; p <= .001) and body image distortions (OR = .77; 95% CI = .68-.85; p = .005) were retained. High levels of hopelessness, impaired emotional functioning and body image distortions are the main factors associated with psychological distress in patients with advanced cancer. Potential interventions to modify these factors in palliative units are discussed. PMID- 27271214 TI - Band Engineering by Controlling vdW Epitaxy Growth Mode in 2D Gallium Chalcogenides. AB - Atomically thin quasi-2D GaSe flakes are synthesized via van der Waals (vdW) epitaxy on a polar Si (111) surface. The bandgap is continuously tuned from its commonly accepted value at 620 down to the 700 nm range, only attained previously by alloying Te into GaSe (GaSex Te1- x ). This is accomplished by manipulating various vdW epitaxy kinetic factors, which allows the choice bet ween screw dislocation-driven and layer-bylayer growth, and the design of different morphologies with different material-substrate interaction (strain) energies. PMID- 27271215 TI - Toward Fluorescence-Based High-Throughput Screening for Enantiomeric Excess in Amines and Amino Acid Derivatives. AB - A highly accurate and reliable screening method for enantiomeric excess of amine derivatives in the presence of water is reported. The fluorescence-based screening system has been realized by self-assembly of chiral diol-type dyes (BINOL, VANOL and VAPOL), 2-formylphenylboronic acid, and chiral amines forming iminoboronate esters. The structure and chirality of the amine analytes determine the stability of the diastereomeric iminoboronate esters, which in turn display differential fluorescence. The fluorescence signal reflects the enantiomeric purity of the chiral amines and was utilized in high-throughput arrays. The arrays were able to recognize enantiomeric excess of amines, amino esters, and amino alcohols. In addition to qualitative analysis, quantitative experiments were successfully performed. Studies of the role of additives such as water or citrate were carried out to gain insight into the stability of the iminoboronate esters. It is shown that the above additives destabilize less stable esters while the stable esters remain unchanged. Thus, the presence of water and citrate leads to increased difference between the diastereomeric iminoboronates and contributes to the enantiodiscrimination of the chiral amines. PMID- 27271217 TI - The gamut of primary retroperitoneal masses: multimodality evaluation with pathologic correlation. AB - The retroperitoneum is a large space where primary and metastatic tumors grow silently before clinical signs appear. Neoplastic retroperitoneal diseases may be solid or cystic, primary or secondary and range from benign to aggressive in behavior. Retroperitoneal neoplasms are notable for their widely disparate histologies. The solid primary retroperitoneal neoplasms are extremely uncommon and can be classified based on their tissue of origin into three main categories: mesodermal tumors, neurogenic tumors, and extragonadal germ cell tumors. These tumors can grow to a large size before clinical symptoms occur or become palpable. When symptoms do occur, they are nonspecific. The majority of these masses are malignant and imaging plays a pivotal role in the detection, staging, and pre-operative planning. Benign and malignant masses should be distinguished whenever possible to avoid unnecessary surgical procedures. Macroscopic fat, calcification, necrosis, vascularity, and neural foraminal widening are common imaging features helping for tumor differentiation. Meticulous cross-sectional imaging can triage the patient to the most appropriate therapy. Tumor morphology dictates imaging character, and biologic activity is reflected by positron emission tomography (PET). Complete surgical excision with tumor free margins is essential for long-term survival. Biopsy should be performed in consultation with surgical oncology to avoid complicating curative surgery. This pictorial essay illustrates the spectrum of multidetector computed tomography (MDCT) imaging findings in common and uncommon primary retroperitoneal masses, with an emphasis on cross-sectional imaging features for an adequate tumor characterization and staging. PMID- 27271216 TI - Design of an alpha-helical antimicrobial peptide with improved cell-selective and potent anti-biofilm activity. AB - AR-23 is a melittin-related peptide with 23 residues. Like melittin, its high alpha-helical amphipathic structure results in strong bactericidal activity and cytotoxicity. In this study, a series of AR-23 analogues with low amphipathicity were designed by substitution of Ala1, Ala8 and Ile17 with positively charged residues (Arg or Lys) to study the effect of positively charged residue distribution on the biological viability of the antimicrobial peptide. Substitution of Ile17 on the nonpolar face with positively charged Lys dramatically altered the hydrophobicity, amphipathicity, helicity and the membrane-penetrating activity against human cells as well as the haemolytic activity of the peptide. However, substitution on the polar face only slightly affected the peptide biophysical properties and biological activity. The results indicate that the position rather than the number of positively charged residue affects the biophysical properties and selectivity of the peptide. Of all the analogues, A(A1R, A8R, I17K), a peptide with Ala1-Arg, Ala8-Arg and Ile17-Lys substitutions, exhibited similar bactericidal activity and anti-biofilm activity to AR-23 but had much lower haemolytic activity and cytotoxicity against mammalian cells compared with AR-23. Therefore, the findings reported here provide a rationalization for peptide design and optimization, which will be useful for the future development of antimicrobial agents. PMID- 27271218 TI - Diagnostic performance of diffusion-weighted magnetic resonance imaging in differentiating human renal lesions (benignity or malignancy): a meta-analysis. AB - PURPOSE: This study aims to quantitatively evaluate the potential of diffusion weighted magnetic resonance imaging (DW-MRI) for differentiating malignant and benign human renal lesions. MATERIALS AND METHODS: A systematic literature was performed to identify previous research related to the diagnostic performance of DW-MRI for determining whether human renal lesions were benign or malignant. ADC values were extracted from normal renal tissue and different lesion types. Data were extracted to assess the diagnostic performance of DW-MRI for differentiating malignant and benign human renal lesions, as well as running threshold effect and heterogeneity. RESULTS: Nine publications with 11 subsets were eligible for data extraction and diagnostic performance calculation. A total of 988 apparent diffusion coefficient (ADC) measurements were included. The differences in ADC values between benign lesions (2.47 +/- 0.81 * 10(-3) mm(2)/s) and malignant lesions (1.81 +/- 0.41 * 10(-3) mm(2)/s) were statistically significant (P < 0.001). The diagnostic odds ratio, the overall positive, negative likelihood ratios, pooled weighted sensitivity and specificity with 95% CI were 20.05 (95% CI 12.56-32.02), 3.32 (95% CI 2.13-5.18), 0.20 (95% CI 0.15-0.27), 88% (95% CI 0.84-0.91) and 72% (95% CI 0.67-0.76), respectively. The area under the curve of the summary receiver operating characteristic was 0.90. CONCLUSIONS: This meta analysis indicated that DW-MRI had a relatively good diagnostic accuracy in differentiating malignant and benign human renal lesions. We preliminarily recommend that DW-MRI is performed with a maximum b value ranging from 800 to 1000 s/mm(2) at 3.0 T for imaging protocol, and that DW-MRI should be used with caution when the study population includes children. PMID- 27271219 TI - Does hepatobiliary phase sequence qualitatively outperform unenhanced T1-weighted imaging in assessment of the ablation margin 24 hours after thermal ablation of hepatocellular carcinomas? AB - PURPOSE: To retrospectively determine whether hepatobiliary phase (HBP) sequence outperforms unenhanced T1-weighted imaging (uT1wI) in distinguishing the ablation margin (AM) from hepatocellular carcinoma (HCC) 24 h after thermoablation. MATERIAL AND METHODS: Ninety-one patients [mean age, 65.7 years; 68 M/23F] with 138 HCCs (>6 months follow-up) underwent pre- and postablation gadoxetate disodium-enhanced MRI. AM showed a hyperintense middle zone (MZ) surrounding central hypo- or hyperintense HCCs on uT1wI, and an intermediate-intense MZ encompassing central hypo- or hyperintense HCCs during HBP. The visible AM was defined as persistent MZ around HCCs, which were demarcated from MZ, or peripherally band encompassing MZ, which were not demarcated from HCC. The indefinite AM was defined as no demarcating HCCs from MZ. The ability to distinguish AM from HCC was classified as visible or indefinite on axial (ax) uT1wI, ax-HBP, coronal (cor)-HBP, and combined all images. To investigate the AM visibility during HBP, significance of differences upon comparison of ax-uT1wI with combined images was analyzed. Preablation liver-tumor contrast ratio (LTCR) on ax-uT1wI and ax-HBP sequence is compared between the visible and indefinite AM. RESULTS: The McNemar test demonstrated a significant increase (p < 0.05) in visible AM from ax-uT1wI (60), to ax-HBP (70), cor-HBP (79), and combined images (83). TLCR with visible AM was significantly higher than that with indefinite AM on ax-uT1wI (0.4 vs. 0.2, p = 0.001) and ax-HBP sequence (0.9 vs. 0.6, p = 0.004). CONCLUSIONS: HBP sequence might have higher feasibility to distinguish AM from tumor than ax-uT1wI. The TLCR value in visible AM was higher than that in indefinite AM on both ax-uT1wI and ax-HBP sequences. PMID- 27271222 TI - Metabolic programming in chronically stimulated T cells: Lessons from cancer and viral infections. AB - T-cell metabolism is central to the shaping of a successful immune response. However, there are pathological situations where T cells are rendered dysfunctional and incapable of eliminating infected or transformed cells. Here, we review the current knowledge on T-cell metabolism and how persistent antigenic stimulation, in the form of cancer and chronic viral infection, modifies both metabolic and functional pathways in T cells. PMID- 27271225 TI - Proteolytic disassembly of peptide-mediated graphene oxide assemblies for turn-on fluorescence sensing of proteases. AB - Molecule-induced assembly of nanomaterials can alter their unique chemical and physical properties, which can be a promising approach for sensing. Herein, we demonstrate an optical 'turn-on' biosensor for the detection of matrix metalloproteinase-2 (MMP-2), fabricated by means of a peptide-induced assembly of fluorescent graphene oxide (GO). Functionalization of GO with a peptide substrate for MMP-2 bearing a thiol group leads to its self-assembly via disulfide bonding, accompanied by self-quenching of GO's strong fluorescence. This peptide-induced GO assembly is then disassembled by proteolytic cleavage in the presence of MMP 2, thereby restoring the level of self-quenched GO fluorescence. With this approach, we are able to detect MMP-2 and to investigate the kinetic parameters of MMP-2 activity. The GO-peptide assembly is successfully applied to the selective and sensitive detection of MMP-2 secreted by living cells, human hepatocytes HepG2, at a concentration of 2 ng mL(-1). PMID- 27271223 TI - Summer diapause induced by high temperatures in the oriental tobacco budworm: ecological adaptation to hot summers. AB - Summer diapause in Helicoverpa assulta (Hubner), which prolongs the pupal stage, particularly in males, is induced by high temperatures. In the laboratory, 3(rd) , 4(th)-, 6(th)-instar and prepupal larvae were exposed to high temperatures - 33 and 35 degrees C with a photoperiod of LD16:8 - until pupation to induce summer diapause. The results showed that the incidence of summer diapause was influenced by temperature, stage exposed, and sex. The higher the temperature, the more often summer diapause was attained. Sixth-instar and prepupal larvae were the sensitive stages for summer diapause induction. H. assulta summer-diapausing pupae needed diapause development to resume development when temperatures became favorable. Furthermore, both body mass and energy storage capacity (lipid and glycogen) were significantly affected by diapause rather than sex, and were significantly higher in summer-diapausing pupae than in non-diapausing pupae. In addition, the body mass loss and respiration rate showed that the rate of metabolism in the summer-diapausing pupae was consistently lower than in non diapausing pupae, which were significantly affected by diapause and pupal age. We conclude that summer diapause in H. assulta is a true diapause, and H. assulta has evolved mechanisms to accumulate energy storage and to lower its metabolism to adapt to hot summers. PMID- 27271226 TI - A parent-directed intervention for addressing academic risk in Latino survivors of childhood leukemia: results of a pilot study. PMID- 27271227 TI - Overexpression of FLT3-ITD driven by spi-1 results in expanded myelopoiesis with leukemic phenotype in zebrafish. PMID- 27271229 TI - Bladder cancer: working towards better outcomes. PMID- 27271228 TI - Smad4 in osteoblasts exerts a differential impact on HSC fate depending on osteoblast maturation stage. AB - Osteoblasts (OBs) are indispensable for the maintenance of hematopoietic stem cells (HSCs) in the bone marrow microenvironment. Here we investigated how Smad4 modulates HSC fate at distinct stages of OB development. For this, we conditionally knocked out Smad4 in cells expressing type I collagen (Col1a1) and osteocalcin (OC), respectively. Col1a1-expressing OBs were widely present in both the trabecular and cortical compartment, whereas OC-expressing OBs were predominantly located in the cortical compartment. HSCs from Col1a1 mutants displayed senescence-associated phenotypes. OC mutants did not exhibit HSC senescence-related phenotypes, but instead showed preferential HSC death. Of note, stromal cell-derived factor 1 expression was lower in Col1a1 mutants than control littermates, suggesting potential impairment of CXCR4-CXCL12-mediated HSC retention. Disruption of the CXCR4-CXCL12 axis by AMD3100 administration led to an increase in the senescence-associated beta-galactosidase activity and low competitive potential. Collectively, our findings indicate that deletion of Smad4 in OBs differentially modulates HSC fate in a stage-dependent manner. PMID- 27271230 TI - Update on novel imaging techniques for the detection of lymph node metastases in bladder cancer. AB - Staging of muscle-invasive bladder cancer (MIBC) remains a challenge. It is generally acknowledged that the most commonly used imaging techniques have a trend to either upstage or downstage the disease. The aim of this review article is to evaluate the currently available scientific evidence for the use of imaging modalities in preoperative bladder cancer staging with special attention to the detection of lymph node metastasis (LNM). A non-systematic literature search utilizing PubMed database with terms MIBC and LN and MRI or PET or CT was performed with the search limited to articles published between 2010 and 2015. Magnetic resonance imaging (MRI) has shown potential for local tumor detection and staging in multiple studies, but the accuracy for LNM detection remains disappointingly low. The LN staging accuracy is improved with the use of ultra small super-paramagnetic particles of iron oxide (USPIO). This experimental method, however, is not commercially available at the moment. Positron emission tomography (PET), a functional imaging technique most commonly accompanied with computed tomography (PET-CT), may also have a role in the detection of bladder cancer LNM in the future. According to the currently available scientific evidence, the following could be recommended for MIBC staging: 1. use of pelvic MRI for primary tumor evaluation and local LNM detection acknowledging limited nodal imaging accuracy; 2. pelvic/abdominal/chest CT for evaluation of distant metastasis. The scientific evidence does not support the routine use of PET-CT (18F-FDG, 18F/11C-choline, 11C-acetate) in bladder cancer staging or in LNM detection. PMID- 27271231 TI - Self-catheterization activity in women with quadriplegia: occupational therapy and achievement of independence. PMID- 27271232 TI - The Effect of Position on PaCO2 and PETCO2 in Patients Undergoing Cervical Spine Surgery in Supine and Prone Position. AB - BACKGROUND: As per American Society of Anesthesiologists guidelines, continuous monitoring of end tidal carbon dioxide (PETCO2) is recommended as standard II basics of anesthetic monitoring especially to ensure adequate ventilation during all anesthetics. Continuous monitoring of PETCO2 can also be used as a guide to maintain the partial pressure of carbon dioxide in arterial blood (PaCO2) to desired level during the surgery. AIMS AND OBJECTIVES: To study the effect of position on PaCO2 and PETCO2 during cervical spine surgery in prone position. MATERIALS AND METHODS: Following institutional ethical committee approval and written informed consent, a prospective study was conducted in 40 patients of 18 to 60 years and of American Society of Anesthesiologists I and II scheduled for cervical spine surgery in prone position. In operating room, the patient is connected to standard monitoring and intravenous access was secured. A 20 G arterial cannula was placed. General anesthesia administered and oral endotracheal intubation done. Baseline values of systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, temperature, SpO2, Ppeak, Pmean, and Pplateau were measured in supine position. For each patient the capnometer was calibrated before use. The P(a-ET)CO2 was calculated in supine position (S1). The PaCO2 and ETCO2 were measured after prone positioning P1, at each subsequent hour (P2, P3, P4), and on completion of the procedure in supine position (S2). The mean values were used for further analysis. RESULTS: The PETCO2 and PaCO2 decreased significantly in cervical spine surgery patients with change of position from supine to prone with no significant change in arterial to end tidal CO2 gradient (P(a-ET)CO2). CONCLUSIONS: PETCO2 can be used as a reliable guide to estimate PaCO2 during cervical spine procedures in prone position. PMID- 27271233 TI - Obscure Retropharyngeal Mucocutaneous Masses Associated With Acoustic Neurofibromatosis: A Source of Difficult Airway Management. PMID- 27271234 TI - The Power of Raw Data. PMID- 27271235 TI - Cerebral Oxygenation Under General Anesthesia Can Be Safely Preserved in Patients in Prone Position: A Prospective Observational Study. AB - BACKGROUND: The effects of prone position (PP) on cerebral tissue metabolism are not well known. The aim of this investigation was to evaluate regional cerebral oxygen desaturation in patients undergoing lumbar spine surgery in PP during routine anesthesia management. MATERIALS AND METHODS: Between July 2013 and October 2013, 50 consecutive patients undergoing lumbar spine surgery under general anesthesia in PP were enrolled. The anesthetic technique was standardized. Using near-infrared spectroscopy, bilateral regional cerebrovascular oxygen saturation was recorded during the surgery. RESULTS: After 30 and 60 minutes of prone repositioning, significant decreases in bilateral regional cerebral oxygen saturation were observed compared with the values in the supine position (from 76.24% to 73.18% at 30 min and 72.76% at 60 min on the right side and from 77.06% to 73.76% at 30 min and 72.92% at 60 min on the left side; P<0.05). These changes were not clinically important and returned to supine values after 90 minutes of prone positioning. Decreases in cerebral oxygen saturation were accompanied by reductions in heart rate and mean arterial pressure (P<0.05). Older age and higher perioperative risk had a significant effect on the reduction of cerebral oxygen values (P<0.05). CONCLUSIONS: The results of our study show that margin of safety against impaired cerebral oxygenation can be maintained in PP. Preventing bradycardia and arterial hypotension is crucial. Older patients and those at higher perioperative risk need more meticulous attention. PMID- 27271236 TI - Anesthetic Challenges in the Management of Distal Posterior Cerebral Artery Aneurysm for Surgical Clipping: A Report of 2 Cases. PMID- 27271237 TI - The Trigemino-cardiac Reflex: Is Treatment With Atropine Still Justified? PMID- 27271238 TI - Nanoparticles and capillary electrophoresis: A marriage with environmental impact. AB - The impact of nanomaterials in the environment and human health is a cause of big concern and even though intensive studies are currently being carried out, there is still a lot to elucidate. The development of validated methods for the characterization and quantification of nanomaterials and their impact on the environment should be encouraged to achieve a proper, safe, and sustainable use of nanoparticles (NPs). Recently, CE emerged as a well-adapted technique for the analysis of environmental samples. This review presents the application of NPs together with CE systems for environmental pollutants analysis, as well as the application of CE techniques for the analysis of various types of NPs. PMID- 27271239 TI - Cryosurgery would be An Effective Option for Clinically Localized Prostate Cancer: A Meta-analysis and Systematic Review. AB - Cryosurgery (CS) has been used on patients with clinically localized PCa for more than 10 years. However, clinical studies evaluating its effectiveness and safety have reported conflicting results. This systematic assessment was performed to obtain comprehensive evidence regarding the potential benefits and safety of CS compared with those of radiotherapy (RT) and radical prostatectomy (RP), respectively. All controlled trials comparing CS with RT or RP and single-arm studies reporting results of CS therapy were identified through comprehensive searches of PubMed, the Cochrane Library and Embase. Ten publications from seven trials, with totally 1252 patients, were included in the meta-analysis, which revealed no significant differences in comparisons of CS vs RT and CS vs RP for overall survival and disease specific survival. However, a significantly lower disease-free survival could be observed for CS than RP. Moreover, a systematic review of literature focusing on comparative data of databases and materials of single-arm trials revealed satisfactory survival results in both primary and salvage CS. Our results showed that cryosurgery would be a relatively effective method for clinically localized prostate cancer with survival results comparable to radiotherapy and radical prostatectomy. However, the large percentage of complications caused by cryosurgery should be carefully monitored. PMID- 27271240 TI - Long-term Cognitive and Health Outcomes of School-Aged Children Who Were Born Late-Term vs Full-Term. AB - IMPORTANCE: Late-term gestation (defined as the 41st week of pregnancy) is associated with increased risk of perinatal health complications. It is not known to what extent late-term gestation is associated with long-term cognitive and physical outcomes. Information about long-term outcomes may influence physician and patient decisions regarding optimal pregnancy length. OBJECTIVE: To compare the cognitive and physical outcomes of school-aged children who were born full term or late term. DESIGN, SETTING, AND PARTICIPANTS: We analyzed Florida birth certificates from 1994 to 2002 linked to Florida public school records from 1998 to 2013 and found 1 442 590 singleton births with 37 to 41 weeks' gestation in the Florida Bureau of Vital Statistics. Of these, 1 153 716 children (80.0%) were subsequently located in Florida public schools. Linear and logistic regression models were used to assess the association of gestational age with cognitive and physical outcomes at school age. Data analysis took place between April 2013 and January 2016. EXPOSURES: Late-term (born at 41 weeks) vs full-term (born at 39 or 40 weeks) gestation. MAIN OUTCOMES AND MEASURES: There were a number of measures used, including the average Florida Comprehensive Assessment Test mathematics and reading scores at ages 8 through 15 years; whether a child was classified as gifted, defined as a student with superior intellectual development and capable of high performance; poor cognitive outcome, defined as a child scoring in the fifth percentile of test takers or having a disability that exempted him or her from taking the Florida Comprehensive Assessment Test; and Exceptional Student Education placement owing to orthopedic, speech, or sensory impairment or being hospitalbound or homebound. RESULTS: Of 1 536 482 children born in Florida from singleton births from 1994 to 2002 with complete demographic information, 787 105 (51.2%) were male; 338 894 (22.1%) of mothers were black and 999 684 (65.1%) were married at time of birth, and the mean (SD) age for mothers at time of birth was 27.2 (6.2) years. Late-term infants had 0.7% of an SD (95% CI, 0.001-0.013; P = .02) higher average test scores in elementary and middle school, 2.8% (95% CI, 0.4-5.2; P = .02) higher probability of being gifted, and 3.1% (95% CI, 0.0-6.1; P = .05) reduced probability of poor cognitive outcomes compared with full-term infants. These cognitive benefits appeared strongest for children with disadvantaged family background characteristics. Late-term infants were also 2.1% (95% CI, -0.3 to 4.5; P = .08) more likely to be physically impaired. CONCLUSIONS AND RELEVANCE: There appears to be a tradeoff between cognitive and physical outcomes associated with late-term gestation. Children born late-term performed better on 3 measures of school-based cognitive functioning but worse on 1 measure of physical functioning relative to children born full term. Our findings provide longer-run information for expectant parents and physicians who are considering delivery at full term vs late term. These findings are most relevant to uncomplicated, low-risk pregnancies. PMID- 27271241 TI - To RCT or not to RCT: evidence on effectiveness of return-to-work interventions. PMID- 27271242 TI - Intimate partner violence and pregnant and parenting adolescents in out-of-home care: reflections on a data set and implications for intervention. AB - AIMS AND OBJECTIVES: To present the findings from a data set reflecting intimate partner violence among adolescents who are pregnant and parenting and living in out-of-home care and to analyse these findings in order to generate potential interventions to address this significant issue. BACKGROUND: Because of their developmental stage, coupled with the stress of pregnancy and new parenthood, adolescent women who are pregnant or postpartum are often at a high risk of abuse. Violence may include physical, emotional/psychological, verbal and sexual abuse, along with birth control sabotage and pregnancy coercion. Adolescent mothers in out-of-home care such as foster care, juvenile detention facilities, kinship care or living in complex family circumstances may be at an even higher risk of intimate partner violence related to the increase in stress, conflict and tenuous situations. DESIGN: This descriptive study was designed, using baseline self-report and demographic data, to examine the relationship of pregnancy or parenting among adolescents with a fear of or reported involvement in intimate partner violence. METHODS: A total of 151 sexually active, urban, system-involved youths in out-of-home care were assessed between 2012-2015 with a survey questionnaire assessment of sexual reproductive health behaviours, areas of risk and protective factors. RESULTS: The findings indicated a significant association between ever having been pregnant and fear of intimate partner violence. CONCLUSIONS: In this population, fear of intimate partner violence was prevalent among adolescent mothers, adding to the complexity of an already difficult family situation. Due to the small sample size and the potential correlation between intimate partner violence and adolescent motherhood, future longitudinal studies with larger samples of adolescents residing in out-of-home care are needed to better understand how this relationship impacts adolescent mothers, their children and families. PMID- 27271244 TI - Multi-centre retrospective study of long-term outcomes following traumatic elbow luxation in 37 dogs. AB - OBJECTIVES: Limited guidelines exist regarding the optimal treatment of traumatic canine elbow luxation, and there is a lack of information on long-term functional outcome. Here we report reduction and stabilisation techniques for a series of traumatic elbow luxations and describe clinical outcome plus long-term questionnaire-based follow-up. METHODS: Retrospective review of canine traumatic elbow luxations (2006 to 2013) treated at five referral centres. Data recorded included signalment, luxation aetiology, time to reduction, reduction technique, surgical procedure, post-reduction care and complications. Questionnaire follow up was attempted for all cases with owners completing the Canine Brief Pain Inventory. RESULTS: Thirty-seven dogs were included. The most frequent cause of luxation was road traffic accident (n=22). Twenty cases were treated surgically. Seven dogs suffered major postoperative complications: reluxation (n=6), infection requiring implant removal (n=1). Four of the six reluxations occurred in dogs that had other orthopaedic injuries. Twenty-two owners completed the Canine Brief Pain Inventory questionnaire: there were 13 excellent, 6 very good, 1 good and 2 fair outcomes. Outcome was not associated with the reduction technique. CLINICAL SIGNIFICANCE: Initial closed reduction, followed by surgical stabilisation if unsuccessful, results in good-to-excellent outcomes in the majority of traumatic canine elbow luxations. Reluxation was the most common major complication and there was a higher incidence of reluxation in patients with multiple orthopaedic injuries. PMID- 27271245 TI - Hot carrier multiplication on graphene/TiO2 Schottky nanodiodes. AB - Carrier multiplication (i.e. generation of multiple electron-hole pairs from a single high-energy electron, CM) in graphene has been extensively studied both theoretically and experimentally, but direct application of hot carrier multiplication in graphene has not been reported. Here, taking advantage of efficient CM in graphene, we fabricated graphene/TiO2 Schottky nanodiodes and found CM-driven enhancement of quantum efficiency. The unusual photocurrent behavior was observed and directly compared with Fowler's law for photoemission on metals. The Fowler's law exponent for the graphene-based nanodiode is almost twice that of a thin gold film based diode; the graphene-based nanodiode also has a weak dependence on light intensity-both are significant evidence for CM in graphene. Furthermore, doping in graphene significantly modifies the quantum efficiency by changing the Schottky barrier. The CM phenomenon observed on the graphene/TiO2 nanodiodes can lead to intriguing applications of viable graphene based light harvesting. PMID- 27271246 TI - PCE dechlorination by non-Dehalococcoides in a microbial electrochemical system. AB - The bioremediation of tetrachloroethene (perchloroethene; PCE) contaminated sites generally requires a supply of some fermentable organic substrates as an electron donor. On the other hand, organic substrates can induce the massive growth of microorganisms around the injection wells, which can foul the contaminated subsurface environment. In this study, PCE dechlorination to ethene was performed in a microbial electrochemical system (MES) using the electrode (a cathode polarized at -500 mV vs. standard hydrogen electrode) as the electron donor. Denaturing gel gradient electrophoresis and pyrosequencing revealed a variety of non-Dehalococcoides bacteria dominant in MES, such as Acinetobacter sp. (25.7 % for AS1 in suspension of M3), Rhodopseudomonas sp. (10.5 % for AE1 and 10.1 % for AE2 in anodic biofilm of M3), Pseudomonas aeruginosa (22.4 % for BS1 in suspension of M4), and Enterobacter sp. (21.7 % for BE1 in anodic biofilm of M4) which are capable of electron transfer, hydrogen production and dechlorination. The Dehalococcoides group, however, was not detected in this system. Therefore, these results suggest that a range of bacterial species outside the Dehalococcoides can play an important role in the microbial electrochemical dechlorination process, which may lead to innovative bioremediation technology. PMID- 27271247 TI - High Spatial Resolution Imaging of Endogenous Hydrogen Peroxide in Living Cells by Solid-State Fluorescence. AB - Herein, we describe selective imaging of hydrogen peroxide using a precipitating dye conjugated to a boronic acid-based immolative linker. We achieved visualization of endogenous hydrogen peroxide in phagosomes by solid-state two photon fluorescence imaging in living cells with exceptionally high spatial resolution. PMID- 27271248 TI - Left ventricular function during porcine-resuscitated septic shock with pre existing atherosclerosis. AB - BACKGROUND: Reversible, depressed cardiac function is frequently encountered during septic shock and commonly called septic cardiomyopathy. Previous studies demonstrated reduced ejection fraction and left ventricular dilatation in both humans and animal models. However, the majority of the studies in humans excluded pre-existing cardiac disease and animal studies were performed on healthy specimen and/or without vasopressor support during sepsis. In order to more closely mimic the actual patients' conditions on intensive care units and to assess the influence of both cardiac comorbidity and vasopressor support on septic cardiomyopathy, we evaluated the left ventricular function in a porcine model of resuscitated septic shock with pre-existing atherosclerosis. METHODS: Hypercholesterolaemic, atherosclerotic pigs due to homozygous low-density lipoprotein receptor mutation and high-fat diet were anaesthetised and surgically instrumented. Faecal peritonitis was induced by inoculation of autologous faeces into the peritoneal cavity in n = 8 animals; n = 5 pigs underwent sham procedure. Sepsis resuscitation included administration of fluids and noradrenaline. Left ventricular function was analysed via pressure-conductance catheters before, 12 and 24 h after the induction of sepsis. RESULTS: The main findings were impaired ventricular dilatation (no significant change in the left ventricular end diastolic volume) and unchanged ejection fraction in septic pigs with pre existing atherosclerosis. The relaxation time constant tau decreased while dp/dtmax increased. Cardiac nitrotyrosine formation increased while expression of the endogenous hydrogen sulphide (H2S)-producing enzyme cystathionine gamma-lyase (CSE) decreased. CONCLUSIONS: The data of the present study are in conflict with previously published data from healthy animal models, most likely as a result of ongoing resuscitation including noradrenaline treatment or intrinsic pathophysiologic processes of the pre-existing atherosclerosis. Moreover, increased nitrotyrosine formation and decreased expression of CSE suggest the implication of augmented oxidative/nitrosative stress and/or reduced bioavailability of nitric oxide as well as diminished endogenous H2S release in the pathophysiology of septic cardiomyopathy. PMID- 27271249 TI - Tensile Forces Originating from Cancer Spheroids Facilitate Tumor Invasion. AB - The mechanical properties of tumors and the tumor environment provide important information for the progression and characterization of cancer. Tumors are surrounded by an extracellular matrix (ECM) dominated by collagen I. The geometrical and mechanical properties of the ECM play an important role for the initial step in the formation of metastasis, presented by the migration of malignant cells towards new settlements as well as the vascular and lymphatic system. The extent of this cell invasion into the ECM is a key medical marker for cancer prognosis. In vivo studies reveal an increased stiffness and different architecture of tumor tissue when compared to its healthy counterparts. The observed parallel collagen organization on the tumor border and radial arrangement at the invasion zone has raised the question about the mechanisms organizing these structures. Here we study the effect of contractile forces originated from model tumor spheroids embedded in a biomimetic collagen I matrix. We show that contractile forces act immediately after seeding and deform the ECM, thus leading to tensile radial forces within the matrix. Relaxation of this tension via cutting the collagen does reduce invasion, showing a mechanical relation between the tensile state of the ECM and invasion. In turn, these results suggest that tensile forces in the ECM facilitate invasion. Furthermore, simultaneous contraction of the ECM and tumor growth leads to the condensation and reorientation of the collagen at the spheroid's surface. We propose a tension based model to explain the collagen organization and the onset of invasion by forces originating from the tumor. PMID- 27271250 TI - Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma. AB - Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a first-line agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the Kaplan-Meier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The log-logistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval <1 from 10 months). The initial probability of cabozantinib conferring superior OS was 54%, falling to 41.5% by month 24. Numerical differences in study-adjusted OS estimates between the two treatments remained small. This study evidences that HR for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in the first months of treatment but nivolumab afterwards, a possible indication that patients with poor prognosis benefit more from cabozantinib in terms of survival, nivolumab benefiting patients with better prognosis. More evidence, including real-world observational data, is needed to compare effectiveness between cabozantinib and nivolumab. PMID- 27271251 TI - Oxidized tea polyphenols prevent lipid accumulation in liver and visceral white adipose tissue in rats. AB - BACKGROUND: Tea polyphenols are the prominent component in tea. After the fermentation process, tea polyphenols are oxidized by polyphenol oxidase to form oxidized tea polyphenols (OTPs). OTPs contain a significant amount of hydrophobic phenyl groups that can bind with non-aqueous materials. Here, we determined whether OTPs can bind with lipids and reduce fat uptake and assessed the effect of OTPs on decreasing obesity and alleviating hyperlipidaemia and other metabolic syndromes. METHODS: Rats were divided into three groups: control, high-fat diet (HFD) and OTP groups. The control and HFD groups were fed a chow diet and a high fat diet, respectively, for 12 weeks; the OTP group was fed a high-fat diet for 6 weeks and then a high-fat diet containing 2 % OTP for 6 weeks. The serum and excrement triglyceride (TAG) and total cholesterol (CHOL) concentrations were determined, and liver tissue and white adipose tissue were collected to detect the expression levels of genes involved in lipid metabolism. RESULTS: Our results revealed that OTPs failed to decrease the serum concentrations of TAG and CHOL. OTPs alleviated the accumulation of lipids in the liver tissue and changed the expression levels of the regulators of lipid metabolism, i.e., peroxisome proliferation-activated receptors (ppars), compared with the rats fed a high-fat diet alone. We also observed a significantly decreased reduction of weight in the visceral white adipose, enhanced regulation of fatty acid beta-oxidation by PPARalpha and enhanced biosynthesis of mitochondria in the visceral white adipose of the OTP rats compared with the HFD rats. Additionally, OTPs promoted the excretion of lipids. CONCLUSION: Our results suggest that OTPs alleviate the accumulation of lipids in liver and visceral white adipose tissue and promote lipid excretion in rats in vivo. PMID- 27271252 TI - Anti-senescence and Anti-inflammatory Effects of the C-terminal Moiety of PTHrP Peptides in OA Osteoblasts. AB - Osteoarthritis (OA) is characterized by degenerative changes in the whole joint leading to physical disability in the elderly population. This condition is associated with altered bone metabolism in subchondral areas suggesting that therapeutic strategies aimed at modifying bone cell metabolism may be of interest. We have investigated the effects of several parathyroid hormone-related protein (PTHrP)-derived peptides (1-37): (N-terminal), (107-111) and (107-139) (C terminal) on senescence features induced by inflammatory stress in human OA osteoblasts. Incubation of these primary cells with interleukin(IL)-1beta led to an increased expression of senescence markers senescence-associated-beta galactosidase activity, gammaH2AX foci, p16, p21, p53, and caveolin-1. PTHrP (107 111) and PTHrP (107-139) significantly reduced all these parameters. Both peptides decreased the production of IL-6 and prostaglandin E2 which was the consequence of cyclo-oxygenase-2 downregulation. PTHrP (107-139) also reduced tumor necrosis factor-alpha release. These anti-inflammatory effects would be related to the reduction of nuclear factor-kappaB activation by both peptides and activator protein-1 by PTHrP (107-139). The three PTHrP peptides favored osteoblastic function although the C-terminal domain of PTHrP was more efficient than its N-terminal domain. Our data support an anti-senescence and anti inflammatory role for the C-terminal moiety of PTHrP with potential applications in chronic inflammatory conditions such as OA. PMID- 27271254 TI - Erratum to: Western Pine Beetle Populations in Arizona and California Differ in the Composition of Their Aggregation Pheromones. PMID- 27271253 TI - Metabolic Rate and Perceived Exertion of Walking in Older Adults With Idiopathic Chronic Fatigue. AB - BACKGROUND: Fatigue is a common complaint in older adults, often not associated with underlying medical conditions. The purpose of this study was to investigate metabolic rate (MR) of walking, walking performance, and perception-based exertion during walking in older adults with and without idiopathic chronic fatigue (ICF). METHODS: 20 older adults (aged 70.8+/-4.9 years), reporting 2 SD above normative values of the Functional Assessment of Chronic Illness Therapy Fatigue scale and without overt health conditions that explained their symptoms, were compared with 25 age-matched older adults (73.2+/-5.1 years) without fatigue symptoms. Participants walked 400 m at a rapid pace on a 20-m course. On a separate visit, oxygen consumption was measured during treadmill test at standard (40.2 m/min), preferred paces (40-83 m/min) and peak capacity. Ratings of perceived exertion (RPE) were measured at each treadmill stage and after each lap of the 400-m walk test. RESULTS: During the 400-m walk test, individuals with ICF showed lower overall walking speed and reported a steady increase in RPE with no change observed in non-fatigued group (1.63+/-1.72 vs 0.27+/-0.68, p < .01). Similar findings on RPE were noted on treadmill test. Gross MR, mass-specific MR, mass-specific net MR, and MR as a percent of peak oxygen consumption of walking were similar between groups during standard, preferred paces and peak capacity on treadmill. CONCLUSIONS: This study suggests that ICF in older adults is not related to elevated metabolic cost of walking. Higher RPE without concomitant decreases in performance indicate a potential disconnect between metabolic output and sensations during movement. PMID- 27271255 TI - Retraction Note to: Involvement of a Specific Chemosensory Protein from Bactrocera dorsalis in Perceiving Host Plant Volatiles. PMID- 27271259 TI - [Not Available]. PMID- 27271256 TI - A retinoic acid receptor beta2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease. AB - : Hepatic stellate cells (HSCs) are an important cellular target for the development of novel pharmacological therapies to prevent and treat nonalcoholic fatty liver diseases (NAFLD). Using a high fat diet (HFD) model of NAFLD, we sought to determine if synthetic selective agonists for retinoic acid receptor beta2 (RARbeta2) and RARgamma can mitigate HSC activation and HSC relevant signaling pathways during early stages of NAFLD, before the onset of liver injury. We demonstrate that the highly selective RARbeta2 agonist, AC261066, can reduce the activation of HSCs, marked by decreased HSC expression of alpha-smooth muscle actin (alpha-SMA), in mice with HFD-induced NAFLD. Livers of HFD-fed mice treated with AC261066 exhibited reduced steatosis, oxidative stress, and expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFalpha), interleukin 1beta (IL-1beta), and monocyte chemotactic protein-1 (MCP 1). Kupffer cell (macrophage) expression of transforming growth factor-beta1 (TGF beta1), which plays a critical role in early HSC activation, was markedly reduced in AC261066-treated, HFD-fed mice. In contrast, HFD-fed mice treated with an RARgamma agonist (CD1530) showed no decreases in steatosis, HSC activation, or Kupffer cell TGF-beta1 levels. In conclusion, our data demonstrate that RARbeta2 is an attractive target for development of NAFLD therapies. KEY MESSAGES: * Hepatic stellate cells (HSCs) are an important pharmacological target for the prevention of nonalcoholic fatty liver diseases (NAFLD). * Retinoids and retinoic acid receptors (RARs) possess favorable metabolic modulating properties. * We show that an agonist for retinoic acid receptor-beta2 (RARbeta2), but not RARgamma, mitigates HSC activation and NAFLD. PMID- 27271257 TI - [Sarcoma of the spleen with MDM2 expression]. AB - Primary sarcomas and sarcoma metastases are a rarity in the spleen. We report on the case of a 69-year-old male patient presenting with unclear abdominal symptoms and computed tomography (CT) revealed a tumor mass in the spleen. Histologically the tumor mass predominantly showed features of a spindle cell sarcoma with lymphoid infiltrates. The expression and amplification of MDM2 could be demonstrated by means of immunohistochemistry and fluorescence in situ hybridization (FISH). Furthermore, staging examinations did not reveal indications of any other primary tumors. These preliminary findings were suggestive of a dedifferentiated liposarcoma; however, in the further diagnostic work-up the tumor showed strong expression of CD21 and CD23 and was ultimately diagnosed as a follicular dendritic cell sarcoma (FDCS). The case emphasizes that MDM2 expression represents a possible pitfall in the diagnosis of spindle cell tumors. The differential diagnostic distinction between FDCS and a dedifferentiated liposarcoma is discussed. PMID- 27271260 TI - [Not Available]. PMID- 27271258 TI - [The WHO/ISUP grading system for renal carcinoma]. AB - Histological tumor grading is an accepted prognostic parameter of renal cell carcinoma (RCC). In 2012, the International Society of Urologic Pathologists (ISUP) proposed a novel grading system for RCC, mainly based on the evaluation of nucleoli: grade 1 tumors have nucleoli that are inconspicuous and basophilic at *400 magnification; grade 2 tumors have nucleoli that are clearly visible at *400 magnification and eosinophilic; grade 3 tumors have clearly visible nucleoli at *100 magnification; and grade 4 tumors have extreme pleomorphism or rhabdoid and/or sarcomatoid morphology. This grading system was validated for clear cell renal cell carcinoma and papillary renal cell carcinoma. At the same time, the ISUP proposed not grading chromophobe renal cell carcinomas according to this system. At a consensus conference in Zurich the World Health Organization (WHO) recommended the ISUP grading system; thus, the WHO/ISUP grading system is now going to be implemented internationally. The ISUP/WHO grading system has not been validated as a prognostic parameter for other tumor subtypes, but can be used for descriptive purposes. PMID- 27271261 TI - Direct determination of phosphate sugars in biological material by (1)H high resolution magic-angle-spinning NMR spectroscopy. AB - The study aim was to unambiguously assign nucleotide sugars, mainly UDP-X that are known to be important in glycosylation processes as sugar donors, and glucose phosphates that are important intermediate metabolites for storage and transfer of energy directly in spectra of intact cells, as well as in skeletal muscle biopsies by (1)H high-resolution magic-angle-spinning (HR-MAS) NMR. The results demonstrate that sugar phosphates can be determined quickly and non-destructively in cells and biopsies by HR-MAS, which may prove valuable considering the importance of phosphate sugars in cell metabolism for nucleic acid synthesis. As proof of principle, an example of phosphate-sugar reaction and degradation kinetics after unfreezing the sample is shown for a cardiac muscle, suggesting the possibility to follow by HR-MAS NMR some metabolic pathways. Graphical abstract Glucose-phosphate sugars (Glc-1P and Glc-6P) detected in muscle by 1H HR MAS NMR. PMID- 27271262 TI - Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt. AB - Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase P1 (GSTP1) genes are involved in the metabolism of many carcinogens. Polymorphisms in these genes with altered enzyme activity have been reported. The present study evaluated the synergistic effect between CYP1A1 and GSTP1 gene polymorphisms and smoking on development of HCV-related liver disease and hepatocellular carcinoma (HCC). The patients group comprised 40 patients with HCC and 40 patients with liver cirrhosis. The control group comprised 40 healthy subjects having no history of malignancy. The genetic polymorphisms were studied using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) technique on blood samples. The number of current or former smoker among HCC and cirrhotic patients as well as the median Pack/year of cigarette smoked were significantly higher in HCC and liver cirrhotic patients than in control group. Subjects with CYP1A1 gene variants (m1 and m3) had no significant risk to develop cirrhosis or HCC compared to control group. Individuals carrying the Ile/Val genotype of GSTP1 had a significant increased risk of HCC (OR of 2.2, 95 % CI 1.143-4.261) and had larger tumor size. No significant risk was observed on combining both genes variants or on combining smoking with variants of both genes. In conclusion, the GSTP1 Ile/Val genotype and Val allele are associated with an increased risk of HCC. CYP1A1 and GSTP1 genes variants interaction did not increase the risk of HCC. PMID- 27271263 TI - Therapeutic Coronary Reperfusion and Reperfusion Injury: An Introduction. PMID- 27271264 TI - Muscle electrical stimulation improves neurovascular control and exercise tolerance in hospitalised advanced heart failure patients. AB - BACKGROUND: We investigated the effects of muscle functional electrical stimulation on muscle sympathetic nerve activity and muscle blood flow, and, in addition, exercise tolerance in hospitalised patients for stabilisation of heart failure. METHODS: Thirty patients hospitalised for treatment of decompensated heart failure, class IV New York Heart Association and ejection fraction <= 30% were consecutively randomly assigned into two groups: functional electrical stimulation (n = 15; 54 +/- 2 years) and control (n = 15; 49 +/- 2 years). Muscle sympathetic nerve activity was directly recorded via microneurography and blood flow by venous occlusion plethysmography. Heart rate and blood pressure were evaluated on a beat-to-beat basis (Finometer), exercise tolerance by 6-minute walk test, quadriceps muscle strength by a dynamometer and quality of life by Minnesota questionnaire. Functional electrical stimulation consisted of stimulating the lower limbs at 10 Hz frequency, 150 ms pulse width and 70 mA intensity for 60 minutes/day for 8-10 consecutive days. The control group underwent electrical stimulation at an intensity of < 20 mA. RESULTS: Baseline characteristics were similar between groups, except age that was higher and C reactive protein and forearm blood flow that were smaller in the functional electrical stimulation group. Functional electrical stimulation significantly decreased muscle sympathetic nerve activity and increased muscle blood flow and muscle strength. No changes were found in the control group. Walking distance and quality of life increased in both groups. However, these changes were greater in the functional electrical stimulation group. CONCLUSION: Functional electrical stimulation improves muscle sympathetic nerve activity and vasoconstriction and increases exercise tolerance, muscle strength and quality of life in hospitalised heart failure patients. These findings suggest that functional electrical stimulation may be useful to hospitalised patients with decompensated chronic heart failure. PMID- 27271265 TI - Children with Dry Skin and Atopic Predisposition: Outcome Measurement with Validated Scores for Atopic Dermatitis. AB - BACKGROUND: Dry skin is a common skin condition in childhood. Few studies exist investigating the influence of daily skin care on dry skin in infants at risk of developing atopic dermatitis (AD). We aimed to assess the effect of skin care on dry skin in this special cohort using validated scores for AD and analysis of skin microtopography. METHODS: 43 children were randomized to group 1 (G1) and group 2 (G2) and 22 infants to group 3 (G3). During 16 weeks, G1 and G3 applied daily a plant-based emollient and G2 a petrolatum-based emollient. The core outcome was assessed by Severity Scoring of Atopic Dermatitis (SCORAD) and Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD). The influence on the parents' life was evaluated by a questionnaire and microtopography by Visioscan(r) VC 98. RESULTS: The SCORAD index declined significantly until week (W) 16 in all groups (p <= 0.041). The sleeplessness score analyzed by PO-SCORAD was highly reduced after W12 in G1 and after W16 in G2 (p <= 0.030). The influence on the parents' anxiety was reduced in G3 at W12 and W16 (p = 0.016). The Visioscan parameter scaliness strongly diminished at W4 (p <= 0.049) and W16 (p <= 0.013) in all groups. CONCLUSIONS: This trial demonstrates improved skin conditions and sleep following daily emollient application in infants and children having dry skin and being at risk of AD. Especially parents of infants showed a reduced fear that their children might develop AD. Further studies are required to investigate the preventive effect of daily emollient therapy in this special cohort evaluating the outcome measures used in this trial. PMID- 27271266 TI - Intraoperative Frozen Section in "Suspicious for Papillary Thyroid Carcinoma" after Adoption of the Bethesda System. AB - OBJECTIVE: To evaluate the accuracy and utility of intraoperative frozen section examination (iFSE) in patients with a preoperative fine-needle aspiration (FNA) cytology of "suspicious for malignancy" (SFM)-Bethesda V, after the adoption of the Bethesda System for Reporting Thyroid Cytopathology. STUDY DESIGN: Case series with chart review. SETTING: Tertiary medical center. SUBJECTS AND METHODS: All patients with SFM-Bethesda V who underwent thyroid surgery with iFSE between 2010 and 2015 were included. In cases where the iFSE was reported to be malignant, a total thyroidectomy was performed; otherwise, thyroid lobectomy (hemithyroidectomy) was performed. RESULTS: The current series included 47 patients diagnosed preoperatively with FNA cytology of SFM-Bethesda V. The malignancy rate was 74.5% (35 of 47). Twenty-four patients with nonmalignant iFSE results underwent lobectomy during their initial surgery: 12 were subsequently found with benign final histology and did not undergo completion thyroidectomy; the other 12 patients had malignant results on final histology, but only 4 of them underwent completion thyroidectomy. iFSE resulted in a sensitivity and specificity of 65.7% and 100%, respectively, with a positive predictive value of 100% (23 of 23) and a negative predictive value of 50% (12 of 24). Accuracy of the iFSE methodology was 74.5% (35 of 47). CONCLUSIONS: With no significant preoperative clinical or sonographic predictors for thyroid malignancy and given the high specificity of iFSE, our results support the use of iFSE for patients with preoperative FNA cytology of SFM-Bethesda V who are undergoing thyroid surgery, to determine the extent of required surgery. PMID- 27271268 TI - Making Cancer Health Text on the Internet Easier to Read for Deaf People Who Use American Sign Language. AB - People with relatively limited English language proficiency find the Internet's cancer and health information difficult to access and understand. The presence of unfamiliar words and complex grammar make this particularly difficult for Deaf people. Unfortunately, current technology does not support low-cost, accurate translations of online materials into American Sign Language. However, current technology is relatively more advanced in allowing text simplification, while retaining content. This research team developed a two-step approach for simplifying cancer and other health text. They then tested the approach, using a crossover design with a sample of 36 deaf and 38 hearing college students. Results indicated that hearing college students did well on both the original and simplified text versions. Deaf college students' comprehension, in contrast, significantly benefitted from the simplified text. This two-step translation process offers a strategy that may improve the accessibility of Internet information for Deaf, as well as other low-literacy individuals. PMID- 27271267 TI - Forced rather than voluntary exercise entrains peripheral clocks via a corticosterone/noradrenaline increase in PER2::LUC mice. AB - Exercise during the inactive period can entrain locomotor activity and peripheral circadian clock rhythm in mice; however, mechanisms underlying this entrainment are yet to be elucidated. Here, we showed that the bioluminescence rhythm of peripheral clocks in PER2::LUC mice was strongly entrained by forced treadmill and forced wheel-running exercise rather than by voluntary wheel-running exercise at middle time during the inactivity period. Exercise-induced entrainment was accompanied by increased levels of serum corticosterone and norepinephrine in peripheral tissues, similar to the physical stress-induced response. Adrenalectomy with norepinephrine receptor blockers completely blocked the treadmill exercise-induced entrainment. The entrainment of the peripheral clock by exercise is independent of the suprachiasmatic nucleus clock, the main oscillator in mammals. The present results suggest that the response of forced exercise, but not voluntary exercise, may be similar to that of stress, and possesses the entrainment ability of peripheral clocks through the activation of the adrenal gland and the sympathetic nervous system. PMID- 27271269 TI - In vitro and in vivo evaluation of the mechanisms of citalopram-induced hepatotoxicity. AB - Even though citalopram is commonly used in psychiatry, there are several reports on its toxic effects. So, the current study was designed to elucidate the mechanisms of cytotoxic effects of in vitro and in vivo citalopram treatment on liver and the following cytolethal events. For in vitro experiments, freshly isolated rat hepatocytes were exposed to citalopram along with/without various agents. To do in vivo studies liver function enzyme assays and histological examination were performed. In the in vitro experiments, citalopram (500 uM) exposure demonstrated cell death, a marked elevation in ROS formation, mitochondrial potential collapse, lysosomal membrane leakiness, glutathione (GSH) depletion and lipid peroxidation. In vivo biochemistry panel assays for liver enzymes function (AST, ALT and GGTP) and histological examination confirmed citalopram (20 mg/kg)-induced damage. citalopram-induced oxidative stress cytotoxicity markers were significantly prevented by antioxidants, ROS scavengers, MPT pore sealing agents, endocytosis inhibitors, ATP generators and CYP inhibitors. Either enzyme induction or GSH depletion were concomitant with augmented citalopram-induced damage both in vivo and in vitro which were considerably ameliorated with antioxidants and CYP inhibitors. In conclusion, it is suggested that citalopram hepatotoxicity might be a result of oxidative hazard leading to mitochondrial/lysosomal toxic connection and disorders in biochemical markers which were supported by histomorphological studies. PMID- 27271271 TI - Correction: Reinventing Biostatistics Education for Basic Scientists. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002430.]. PMID- 27271270 TI - Clinicopathological differences between variants of the NAB2-STAT6 fusion gene in solitary fibrous tumors of the meninges and extra-central nervous system. AB - Investigations on the NAB2-STAT6 fusion gene in solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) have increased since its discovery in 2013. Although several SFTs reported without NAB2-STAT6 fusion gene analysis, we reviewed 546 SFTs/HPCs with NAB2-STAT6 fusion gene analysis in this study and investigated differences between the gene variants. In total, 452 cases tested positive for the NAB2-STAT6 fusion gene, with more than 40 variants being detected. The most frequent of these were NAB2 exon 6-STAT6 exon 16/17/18 and NAB2 exon 4-STAT6 exon 2/3, with the former occurring most frequently in SFTs in meninges, soft tissues, and head and neck; the latter predominated in SFTs in the pleura and lung. There was no difference between the histology of SFTs and fusion gene variants. A follow-up analysis of SFTs showed that 51 of 202 cases had a recurrence, with 18 of 53 meningeal SFTs having a local recurrence and/or metastasis within 0-19 years. In meninges and soft tissue, SFTs with the NAB2 exon 6-STAT6 exon 16/17/18 tended to recur more frequently than SFTs with the NAB2 exon 4-STAT6 exon 2/3. Clinicopathological data, including yearly follow ups, are required for meningeal SFTs/HPCs to define the correlation of variants of NAB2-STAT6 fusion gene. PMID- 27271272 TI - Kinetics of Clobetasol-17-Propionate in Psoriatic Lesional and Non-Lesional Skin Assessed by Dermal Open Flow Microperfusion with Time and Space Resolution. AB - PURPOSE: To evaluate the kinetics of topically applied clobetasol-17-propionate (CP-17) in lesional and non-lesional psoriatic skin when released from a commercially available low-strength cream using in vivo dermal open-flow microperfusion (dOFM). METHODS: Twelve patients received Dermovate(r) cream (CP 17, 0.05%) on small lesional and non-lesional skin test sites for 14 days, once daily. On day 1 and 14, dOFM samples were continuously taken in the dermis for 24 h post-dose and analyzed by LC-MS/MS. Probe depths were assessed by 50 MHz ultrasound scanning. RESULTS: Mixed-effects modelling identified skin condition, treatment duration and probe-depth as kinetics determining variables. The time- and depth-resolved intradermal data revealed (i) slower penetration of CP-17 into lesional than into non-lesional skin, (ii) normalized (faster) skin penetration after repeated dosing, and (iii) no CP-17 accumulation within the dermis independently of the skin condition. CONCLUSIONS: Intradermal investigation of a highly lipophilic drug released from low-strength cream was successfully performed by using dOFM and timely and spatially, i.e., probe-depth dependent, resolved kinetic data were delivered. These data support the assumption that the thickened psoriatic stratum corneum might act as trap compartment which lowers the skin penetration rate for lipophilic topical drugs. PMID- 27271273 TI - Grape seed proanthocyanidin extract ameliorates murine autoimmune arthritis through regulation of TLR4/MyD88/NF-kappaB signaling pathway. AB - BACKGROUND/AIMS: Grape seed proanthocyanidin extract (GSPE) has been reported to have a beneficial effect on regulating inf lammation. However, the anti inflammatory mechanism of GSPE remains unclear. The aim of this study was to verify the influence of GSPE on the Toll-like receptor 4 (TLR4)-mediated signaling pathway in the regulation of murine autoimmune arthritis. METHODS: Collagen-induced arthritis (CIA) was induced in dilute brown non-agouti (DBA)/1J mice. The mice were treated with GSPE (0 or 100 mg/kg) intraperitoneally. The severity of arthritis was assessed clinically, biochemically, and histologically. Immunostaining for TLR4 was performed. The expressions of TLR4 and downstream signaling molecules were analyzed by Western blot. The effect of GSPE on lipopolysaccharide (LPS)-induced TLR4 activation was also evaluated using RAW264.7 cells and fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis and from those with osteoarthritis. RESULTS: GSPE attenuated the clinical severity of arthritis and decreased histological damage. GSPE treatment reduced the number of TLR4-stained cells in the synovium of mice with CIA. GSPE also downregulated the expression of TLR4, myeloid differentiation factor 88 (MyD88) and phosphorylated IkappaBalpha synovial protein in CIA mice. Concurrently, GSPE inhibited the nuclear translocation of nuclear factor-kappaB (NF-kappaB) subunits (p65 and p50). LPS-induced TLR4 activation was suppressed by GSPE in human FLS as well as in murine macrophages in vitro. CONCLUSIONS: Our results demonstrated that GSPE ameliorated CIA by regulating the TLR4-MyD88-NF kappaB signaling pathway. PMID- 27271275 TI - For staining of ALK protein, the novel D5F3 antibody demonstrates superior overall performance in terms of intensity and extent of staining in comparison to the currently used ALK1 antibody. AB - Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm. Approximately 50 % of IMTs show an anaplastic lymphoma kinase (ALK) gene fusion resulting in ALK overexpression on immunohistochemistry (IHC). A novel anti-ALK monoclonal antibody (D5F3) has been suggested to be of superior sensitivity to the ALK1 antibody which is currently used. We compared the performance of D5F3 in detecting ALK protein expression in IMTs from various anatomic sites compared to the currently utilized ALK1. We selected 25 IMTs from our surgical pathology files (2005-2015). The novel rabbit monoclonal anti-human CD246 (clone D5F3) and the currently used mouse monoclonal anti-human CD246 (clone ALK1) were used for immunohistochemical staining (IHC) in an automated slide stainer. The percentage of immunoreactive tumor cells (0, <5 %, 5-50 %, >50 %) and cytoplasmic staining intensity (graded 0-3) were assessed and compared between the two antibodies. Fluorescence in situ hybridization (FISH) studies for ALK gene rearrangement were performed on 11 tumors. D5F3 antibody stained 76 % and ALK1 antibody stained 72 % of IMTs (p = 0.747). Compared to staining with ALK1, D5F3 stained a higher proportion of cases extensively (>50 % cells) (76 vs. 28 %, p < 0.001) and with high intensity (grade 3 76 % vs 0; p < 0.001). FISH and IHC findings (for both antibodies) were concordant in 9/10 (90 %) IMTs, in which results were informative. The novel anti-ALK rabbit monoclonal antibody (D5F3 clone) demonstrates superior overall performance in term of intensity and extent of staining of ALK protein in IMT. We found IHC staining with both antibody clones to correlate equally well with FISH results for detection of ALK rearrangement. PMID- 27271276 TI - Informal Human Milk Sharing: A Qualitative Exploration of the Attitudes and Experiences of Mothers. AB - BACKGROUND: Little is known about women's participation or likely participation in informal human milk (HM) sharing. The US Food and Drug Administration recommends against feeding infants shared HM acquired directly from individuals or through the Internet. OBJECTIVE: This study explored the experiences of and attitudes toward HM sharing among mothers with experience of HM feeding and breast pump use, regardless of whether or not they had participated in HM sharing. METHODS: We conducted qualitative, semistructured, in-depth interviews with 41 mothers from 4 counties in upstate New York, asking about their attitudes toward HM sharing. Interviews were transcribed and analyzed inductively. RESULTS: Most women were aware of informal HM sharing and some had personal experience with sharing. Many mothers reported a willingness to provide their own HM if they had extra and their own child had enough. Mothers were less trusting about receiving HM, voicing concerns about the dietary intake or disease status of potential providers. Mothers felt that whether or not they participated in HM sharing would depend on the situation; they were most amenable to sharing with a family member or close friend. A novel finding was the involvement of lactation consultants and midwives, who coordinated HM exchanges for mothers in this sample. CONCLUSION: Awareness of HM sharing was high in this sample. Depending on the situation, mothers may consider participating in informal HM sharing and they may be facilitated by health professionals. Future research is required to establish the benefits and risks associated with informal HM sharing. PMID- 27271274 TI - Neuron-specific enolase as a novel biomarker reflecting tuberculosis activity and treatment response. AB - BACKGROUND/AIMS: It is not clear which tests are indicative of the activity and severity of tuberculosis (TB). This study aimed to investigate the predictive value of neuron-specific enolase (NSE) and to determine the origin of NSE in TB patients. METHODS: A single-center retrospective analysis was conducted on newly diagnosed TB patients between January and December 2010. Patients were categorized into one of two disease groups (focal segmental or extensive) based on chest X-ray. Pre- and post-treatment NSE concentrations were evaluated. To determine the origin of serum NSE concentration, NSE staining was compared with macrophage-specific CD68 staining in lung tissues and with a tissue microarray using immunohistochemistry and immunofluorescence. RESULTS: A total of 60 newly diagnosed TB patients were analyzed. In TB patients, NSE serum concentration was significantly increased and NSE level decreased after treatment (p < 0.001). In proportion to serum high-sensitivity C-reactive protein concentration, the mean serum concentration of NSE in the extensive group (25.12 ng/mL) was significantly higher than that in the focal segmental group (20.23 ng/mL, p = 0.04). Immunohistochemical staining revealed a large number of macrophages that stained positively for both NSE and CD68 in TB tissues. In addition, NSE signals mostly co-localized with CD68 signals in the tissue microarray of TB patients. CONCLUSIONS: Our results suggest that NSE may be a practical parameter that can be used to monitor TB activity and treatment response. Elevated serum NSE level originates, at least in part, from macrophages in granulomatous lesions. PMID- 27271277 TI - Video capsule endoscopy: is bowel preparation necessary? AB - There is no standardized protocol for bowel preparation prior to video capsule endoscopy, although one is strongly recommended. The purpose of our study was to see if there was a statistical significance between small bowel mucosal visualization rates for those who received bowel preparation and those who did not. We retrospectively analyzed all patients who had a video capsule endoscopy from August 2014 to January 2016 at a tertiary care center. All patients fasted prior to the procedure. Bowel preparation when used consisted of polyethylene glycol. A long fast consisted of 12 or more hours. The grading system used to assess the small bowel was adapted from a previously validated system from Esaki et al Statistical analyses were performed using Fisher's exact test or Welch's 2 sample t-test and statistical significance was present if the p value was <=0.05. 76 patients were carried forward for analysis. Small bowel mucosal visualization rates were similar between those who received bowel preparation and those who did not (92.5% vs 88.9%, p=0.44). Small bowel mucosal visualization rates were significantly better in those patients who had a long fast compared with those who had a short fast (97.7% vs 81.3%, p=0.019). Our study demonstrates that the addition of bowel preparation prior to video capsule endoscopy does not significantly improve small bowel mucosal visualization rates and, in addition, there is a statistically significant relationship between increased fasting time and improved small bowel mucosal visualization. A prolonged fast without bowel preparation might be satisfactory for an adequate small bowel visualization but further randomized, prospective studies are necessary to confirm these findings. PMID- 27271278 TI - Evidence for a Notch1-mediated transition during olfactory ensheathing cell development. AB - Olfactory ensheathing cells (OECs) are a unique glial population found in both the peripheral and central nervous system: they ensheath bundles of unmyelinated olfactory axons from their peripheral origin in the olfactory epithelium to their central synaptic targets in the glomerular layer of the olfactory bulb. Like all other peripheral glia (Schwann cells, satellite glia, enteric glia), OECs are derived from the embryonic neural crest. However, in contrast to Schwann cells, whose development has been extensively characterised, relatively little is known about their normal development in vivo. In the Schwann cell lineage, the transition from multipotent Schwann cell precursor to immature Schwann cell is promoted by canonical Notch signalling. Here, in situ hybridisation and immunohistochemistry data from chicken, mouse and human embryos are presented that suggest a canonical Notch-mediated transition also occurs during OEC development. PMID- 27271279 TI - Relationship between diverse patient body size- and image acquisition-related factors, and quantitative and qualitative image quality in coronary computed tomography angiography: a multicenter observational study. AB - PURPOSE: We investigated the effects of patient- and image acquisition-related factors on the image quality in coronary CT angiography (CCTA). MATERIALS AND METHODS: We enrolled 1197 patients (728 men; 65 +/- 12 years). All underwent CCTA under the routine scan protocol in 23 participating hospitals. The subjective image quality (3-point Likert scale: excellent, good, and poor) and the attenuation of the left and right coronary artery (LCA, RCA) were recorded; the effects of patient and image acquisition-related factors on vascular attenuation were then compared. RESULTS: The mean LCA attenuation was 515.2 +/- 65.8 (excellent), 401.4 +/- 63.4 (good), and 319.5 +/- 47.6 HU (poor). The corresponding RCA attenuation was 496.6 +/- 67.6, 390.5 +/- 58.5, and 308.5 +/- 50.7 HU, respectively. Univariate analysis revealed significant associations between sufficient coronary attenuation (> 400 HU) and the age, gender, body surface area (BSA), number of detectors, contrast synchronization, scan mode, and the fractional contrast dose. Multivariate analysis revealed that the bolus tracking method, prospective electrocardiogram gating, and fractional contrast dose were significantly associated with sufficient coronary enhancement. CONCLUSION: BSA and fractional contrast dose are the most important patient- and image acquisition-related factors for sufficient coronary attenuation in CCTA. PMID- 27271280 TI - Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1. AB - Bisphenol A (BPA) is a ubiquitous compound emerging as a possible toxicant during embryonic development. Human embryonic stem cell (hESC) promises a valuable model for evaluating the effects of environmental chemicals on human prenatal development. In our study, 1 MUM BPA were applied to hESC-derived embryoid bodies (hEBs) and effects of BPA on neural cell differentiation were investigated. The expression level of insulin-like growth factor 1 (IGF-1) and marker genes for ectoderm, neuron progenitor cells, and dopaminergic (DA) neurons were all repressed upon BPA exposure. The population of hESC-derived neural precursor cells (NPCs) and DA neurons were decreased. Furthermore, yield of DA neuron secreted tyrosine hydroxylase (TH) and dopamine were also reduced. When recombinant IGF-1 supplied, BPA-caused repressions were partially or completely relieved. Our further methylation microarray analysis indicated that there was a higher methylation level on the promoter of SRY-related HMG-box 5 (SOX5), a possible enhancer of IGF-1. Consistently, next quantitative polymerase chain reaction (qPCR) results confirmed that SOX5 expression was downregulated. Our investigation suggests that BPA represses DA neuron differentiation mainly through downregulating IGF-1 expression, which may attribute to the altered methylation level on the promoter of IGF-1 upstream genes. Our findings first elaborate the mechanism of IGF-1-mediated BPA effects on neuronal differentiation, which is helpful to illuminate the unique mechanism of BPA toxicity on prenatal neurodevelopment. PMID- 27271283 TI - Corrigendum: Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway. PMID- 27271284 TI - Fiber-based photon-pair source capable of hybrid entanglement in frequency and transverse mode, controllably scalable to higher dimensions. AB - We have designed and implemented a photon-pair source, based on the spontaneous four wave mixing (SFWM) process in a few-mode fiber, in a geometry which permits multiple, simultaneous SFWM processes, each associated with a distinct combination of transverse modes for the four participating waves. In our source: i) each process is group-velocity-matched so that it is, by design, nearly factorable, and ii) the spectral separation between neighboring processes is greater than the marginal spectral width of each process. Consequently, there is a direct correspondence between the joint amplitude of each process and each of the Schmidt mode pairs of the overall two-photon state. Our approach permits hybrid entanglement in discrete frequency and in transverse mode, whereby control of the number of supported fiber transverse modes allows scalability to higher dimensions while spectral filtering may be used for straightforward Schmidt mode discrimination. PMID- 27271281 TI - Bioinformatics resources for pollen. AB - KEY MESSAGE: Bioinformatics for Pollen. Pollen plays a key role in crop production, and its development is the most delicate phase in reproduction. Different metabolic pathways are involved in pollen development, and changes in the level of some metabolites, as well as responses to stress, are correlated with the reduction in pollen viability, leading consequently to a decrease in the fruit production. However, studies on pollen may be hard because gamete development and fertilization are complex processes that occur during a short window of time. The rise of the so-called -omics sciences provided key strategies to promote molecular research in pollen tissues, starting from model organisms and moving to increasing number of species. An integrated multi-level approach based on investigations from genomics, transcriptomics, proteomics and metabolomics appears now feasible to clarify key molecular processes in pollen development and viability. To this aim, bioinformatics has a fundamental role for data production and analysis, contributing varied and ad hoc methodologies, endowed with different sensitivity and specificity, necessary for extracting added-value information from the large amount of molecular data achievable. Bioinformatics is also essential for data management, organization, distribution and integration in suitable resources. This is necessary to catch the biological features of the pollen tissues and to design effective approaches to identifying structural or functional properties, enabling the modeling of the major involved processes in normal or in stress conditions. In this review, we provide an overview of the available bioinformatics resources for pollen, ranging from raw data collections to complete databases or platforms, when available, which include data and/or results from -omics efforts on the male gametophyte. Perspectives in the fields will also be described. PMID- 27271282 TI - Pollen proteomics: from stress physiology to developmental priming. AB - KEY MESSAGE: Pollen development and stress. In angiosperms, pollen or pollen grain (male gametophyte) is a highly reduced two- or three-cell structure which plays a decisive role in plant reproduction. Male gametophyte development takes place in anther locules where diploid sporophytic cells undergo meiotic division followed by two consecutive mitotic processes. A desiccated and metabolically quiescent form of mature pollen is released from the anther which lands on the stigma. Pollen tube growth takes place followed by double fertilization. Apart from its importance in sexual reproduction, pollen is also an interesting model system which integrates fundamental cellular processes like cell division, differentiation, fate determination, polar establishment, cell to cell recognition and communication. Recently, pollen functionality has been studied by multidisciplinary approaches which also include OMICS analyses like transcriptomics, proteomics and metabolomics. Here, we review recent advances in proteomics of pollen development and propose the process of developmental priming playing a key role to guard highly sensitive developmental processes. PMID- 27271285 TI - Value of diffusion-weighted MR imaging in the diagnosis of lymph node metastases in patients with cholangiocarcinoma. AB - PURPOSE: To evaluate diffusion-weighted MR imaging (DWI) in the diagnosis of lymph node metastases in patients with cholangiocarcinoma. METHODS: In 24 patients with cholangiocarcinoma, MR imaging of the upper abdomen was performed prior to surgery at 1.5 T using a respiratory-triggered single-shot echo-planar imaging (SSEPI) sequence (b values: 50, 300, and 600 s/mm(2)). ADC (apparent diffusion coefficient) values and diameters of regional lymph nodes (LN) were determined. Subsequently, in all patients, surgical exploration and/or resection of the primary tumor and regional LN dissection were performed. Imaging results were correlated with results of histopathologic analysis. ADC values and diameters of benign and malignant LN were compared using the Mann-Whitney U test. In addition, a ROC (receiver operating characteristic curve) analysis was performed. RESULTS: The mean ADC value (*10(-3) mm(2)/s) of metastatic LN (1.21 +/- 0.15) was significantly lower than that of benign LN (1.62 +/- 0.33, p < 0.001) while there was no significant difference in the mean diameter of malignant (16.8 +/- 5.4 mm) and benign LN (14.1 +/- 4.0 mm; p = 0.09). Using an ADC value of 1.25 * 10(-3) mm(2)/s as threshold, 91.4% of LN were correctly classified as benign or malignant with a sensitivity/specificity of 83.3%/92.8% and a positive/negative predictive value of 66.7%/96.7%. The area under the ROC curve was 0.93. CONCLUSION: DWI using a respiratory-triggered SSEPI sequence, according to our preliminary experience, is a promising imaging modality in the differentiation of benign and malignant LN in patients with cholangiocarcinoma. PMID- 27271286 TI - MRI evaluation of complex renal cysts using the Bosniak classification: a comparison to CT. AB - PURPOSE: The purpose of this study was to compare the ability of magnetic resonance imaging (MRI) and computed tomography (CT) to discriminate between benign and malignant cystic renal lesions utilizing the Bosniak classification. MATERIALS AND METHODS: We retrospectively searched our Radiological Information System using renal/kidney cysts as entries. The search retrieved 2929 patients and 525 complex renal cysts. After exclusions, 42 complex cysts, from 37 patients, with CT and MRI, up to six months apart, were included. Surgery and pathology report and follow-up of at least 24 months were used as a standard of reference. RESULTS: The mean age of patients was 51.4 years, ranging from 11 to 82 years old. Twenty-nine lesions were classified as Bosniak I, II or II-F by CT and/or MRI and 13 as Bosniak III or IV, by one of the methods. The interobserver agreement for Bosniak classification for CT was 0.87 and 0.93 for MRI. Fifteen lesions had higher Bosniak categories on MRI, included six with change in management. Only two lesions had a higher category on CT, one with change in management. The frequency of malignancy for Bosniak III was 50 % (2/4) for CT and 20% for MRI (1/5), as Bosniak upgrades by MRI resulted in surgery for benign lesions. Both methods had 100 % frequency of malignancy for category 4. CONCLUSION: MRI led to category migration and management change of complex renal cysts in a significant proportion of cases, likely due to its superior soft tissue and contrast resolution. The impact of MRI on detection and outcomes of malignant complex renal cysts still requires further investigation. PMID- 27271287 TI - Type II SOCS as a feedback repressor for GH-induced Igf1 expression in carp hepatocytes. AB - Type II suppressor of cytokine signaling (SOCS) serve as feedback repressors for cytokines and are known to inhibit growth hormone (GH) actions. However, direct evidence for SOCS modulation of GH-induced insulin-like growth factor 1 (Igf1) expression is lacking, and the post-receptor signaling for SOCS expression at the hepatic level is still unclear. To shed light on the comparative aspects of SOCS in GH functions, grass carp was used as a model to study the role of type II SOCS in GH-induced Igf1 expression. Structural identity of type II SOCS, Socs1-3 and cytokine-inducible SH2-containing protein (Cish), was established in grass carp by 5'/3'-RACE, and their expression at both transcript and protein levels were confirmed in the liver by RT-PCR and LC/MS/MS respectively. In carp hepatocytes, GH treatment induced rapid phosphorylation of JAK2, STATs, MAPK, PI3K, and protein kinase B (Akt) with parallel rises in socs1-3 and cish mRNA levels, and these stimulatory effects on type II SOCS were shown to occur before the gradual loss of igf1 gene expression caused by prolonged exposure of GH. Furthermore, GH induced type II SOCS gene expression could be negated by inhibiting JAK2, STATs, MEK1/2, P38 (MAPK), PI3K, and/or Akt respectively. In CHO cells transfected with carp GH receptor, over-expression of these newly cloned type II SOCS not only suppressed JAK2/STAT5 signaling with GH treatment but also inhibited GH-induced grass carp Igf1 promoter activity. These results, taken together, suggest that type II SOCS could be induced by GH in the carp liver via JAK2/STATs, MAPK, and PI3K/Akt cascades and serve as feedback repressors for GH signaling and induction of igf1 gene expression. PMID- 27271288 TI - Bilateral vestibular hypofunction and Lyme disease: a causal link? PMID- 27271289 TI - Malignant transformation of low-grade gliomas in patients undergoing adjuvant therapy. AB - Low-grade gliomas (LGG) comprise nearly 15-20 % of all central nervous system glial tumors. Several factors have been recognized as playing role in LGG malignant transformation (MT). A breakthrough analysis of a multidisciplinary group pointed that temozolomide may play a role in MT of LGGs. We analyzed the prevalence of MT in LGG patients submitted to adjuvant therapy (AT). We analyzed the medical charts of 43 patients with LGG submitted to surgery or biopsy and attending at Hospital do Servidor Publico Estadual de Sao Paulo (Sao Paulo, Brazil), consecutively diagnosed from 1995 to 2013. 43 patients (24 women and 19 men) were evaluated, with mean age of 45.3 years. According to histology, 30 were astrocytomas (70 %), 12 (27 %) were oligodendrogliomas, and 1 (3 %) were mixed glioma. Mean follow-up time was 4.2 years with the standard deviation of 2.1. Twenty-eight patients did not receive adjuvant therapy and 15 received adjuvant therapy. From 43 patients with complete follow-up, 21 (48 %) experienced malignant transformation. Among such patients, nine were users of AT. Forty-eight percent of patients presented MT, being 60 % in the AT group and 42.8 % without AT. Our analysis revealed a high prevalence of MT in patients undergoing AT, higher than in patients without AT. PMID- 27271291 TI - Co-culture of outgrowth endothelial cells with human mesenchymal stem cells in silk fibroin hydrogels promotes angiogenesis. AB - Sufficient vascularization of the implant construct is required for tissue regeneration to ensure the supply of oxygen and nutrients. In our previous work, we established sonication-induced silk fibroin hydrogel to load neural stem cells for brain tissue engineering applications. In this study, we explored the application of silk fibroin as an injectable hydrogel for vascularization of soft tissues. We investigated the ability of outgrowth endothelial cells (OECs) in mono-culture or in co-culture with human bone marrow-derived mesenchymal stem cells (BM-MSCs) to form capillary networks in silk fibroin hydrogels. Furthermore, the silk fibroin hydrogel was modified with IKVAV peptide revealing a sequence derived from the extracellular matrix component laminin-1 to test its effects on angiogenesis, using unmodified and VVIAK modified silk fibroin hydrogel as controls. In monocultures of OECs, no angiogenic structures were observed in silk fibroin hydrogels. In contrast, vascular structures were abundant and increased in co-culture, as confirmed by immunocytochemistry and scanning electron microscopy (SEM) over 10 d of culture in silk fibroin-based hydrogels. Although no significant differences in angiogenic activity seem to be caused by the IKVAV peptide in our experimental settings, these results indicate that sonication-induced silk fibroin-based hydrogels support the formation of functional endothelial tubes and vascularization networks in the presence of mesenchymal cells supporting the vascular sprouting of endothelial cells. PMID- 27271290 TI - Limited Genetic Diversity of Hepatitis B Virus in the General Population of the Offin River Valley in Ghana. AB - Hepatitis B virus (HBV) infections account for approximately 780,000 deaths per year, most of which occur in the developing world. Co-infection with HBV and hepatitis delta virus (HDV) may lead to the most severe form of viral hepatitis. In Ghana, knowledge on the prevalence of HBV and HDV in the general population is scanty and the few genetic analyses of the prevailing HBV genotypes are dating back more than a decade. In the present study, 1,323 serum samples from individuals living in a rural area (Offin river valley) of Ghana were analyzed for the presence of the hepatitis B surface antigen (HBsAg). Positive sera were subsequently tested for the presence of anti-HDV antibodies. A total of 107 (8%) sera were HBsAg positive with an 8.4% prevalence of anti-HDV antibodies among the HBsAg positives. Phylogenetic analysis based on HBV pre-S/S sequences, attributed all 52 typable samples to genotype E. All belonged to serotype ayw4. While 19 sequences clustered with those from a number of African countries, the other 33 formed a separate cluster distinguished by an intergroup mean distance of 1.5% from the pan-African HBV/E cluster. Successful implementation of HBV vaccination in the region was reflected by the low HBsAg carrier rate of 1.8% among children <=11 years. PMID- 27271292 TI - Pulseq: A rapid and hardware-independent pulse sequence prototyping framework. AB - PURPOSE: Implementing new magnetic resonance experiments, or sequences, often involves extensive programming on vendor-specific platforms, which can be time consuming and costly. This situation is exacerbated when research sequences need to be implemented on several platforms simultaneously, for example, at different field strengths. This work presents an alternative programming environment that is hardware-independent, open-source, and promotes rapid sequence prototyping. METHODS: A novel file format is described to efficiently store the hardware events and timing information required for an MR pulse sequence. Platform dependent interpreter modules convert the file to appropriate instructions to run the sequence on MR hardware. Sequences can be designed in high-level languages, such as MATLAB, or with a graphical interface. Spin physics simulation tools are incorporated into the framework, allowing for comparison between real and virtual experiments. RESULTS: Minimal effort is required to implement relatively advanced sequences using the tools provided. Sequences are executed on three different MR platforms, demonstrating the flexibility of the approach. CONCLUSION: A high level, flexible and hardware-independent approach to sequence programming is ideal for the rapid development of new sequences. The framework is currently not suitable for large patient studies or routine scanning although this would be possible with deeper integration into existing workflows. Magn Reson Med 77:1544 1552, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27271293 TI - A Retrospective Analysis of the Effectiveness of the Longevity Protocol for Assessing the Risk of Implant Failure. AB - BACKGROUND: A new, computerized diagnostic tool, called the Longevity Protocol, was recently developed to predict implant failure. The present retrospective analysis was undertaken to assess the prognostic validity of this protocol. MATERIALS AND METHODS: A selected group of patients who had been treated with implants over the past 10 years at six dental clinics and experienced implant failure were included in the analysis. Another group of patients with similar characteristics, not experiencing implant failure, was used as control. In April of 2015, data about each of the patients was entered into the Longevity Protocol database. For each patient, the risk assessment produced by the protocol was compared to whether the implants eventually failed. The implant failure predictions and actual implant failures were compared. RESULTS: The Longevity Protocol analyzed the possible failure of 595 implants placed in 221 patients (323 implants placed in 138 patients classified as low risk, 180 implants placed in 55 patients classified as moderate risk, and 92 implants placed in 28 patients classified as high risk). The actual percentage of implant failure in the three groups was 10%, 15%, and 22%, respectively. The differences between the groups were statistically significant. The sensitivity and specificity of the Longevity Protocol was 84.9% and 11.90% in the high/moderate risk group and 47.17% and 32.74% in the low risk group, respectively. CONCLUSIONS: Statistically significant results were obtained. The Longevity Protocol reliably identified patients who risked implant failure. The protocol appears to be an important tool for prognosis assessment. PMID- 27271294 TI - Staged-informed Consent in the Cohort Multiple Randomized Controlled Trial Design: Erratum. PMID- 27271296 TI - Transcript Profile of Flowering Regulatory Genes in VcFT-Overexpressing Blueberry Plants. AB - In order to identify genetic components in flowering pathways of highbush blueberry (Vaccinium corymbosum L.), a transcriptome reference composed of 254,396 transcripts and 179,853 gene contigs was developed by assembly of 72.7 million reads using Trinity. Using this transcriptome reference and a query of flowering pathway genes of herbaceous plants, we identified potential flowering pathway genes/transcripts of blueberry. Transcriptome analysis of flowering pathway genes was then conducted on leaf tissue samples of transgenic blueberry cv. Aurora ('VcFT-Aurora'), which overexpresses a blueberry FLOWERING LOCUS T like gene (VcFT). Sixty-one blueberry transcripts of 40 genes showed high similarities to 33 known flowering-related genes of herbaceous plants, of which 17 down-regulated and 16 up-regulated genes were identified in 'VcFT-Aurora'. All down-regulated genes encoded transcription factors/enzymes upstream in the signaling pathway containing VcFT. A blueberry CONSTANS-LIKE 5-like (VcCOL5) gene was down-regulated and associated with five other differentially expressed (DE) genes in the photoperiod-mediated flowering pathway. Three down-regulated genes, i.e., a MADS-AFFECTING FLOWERING 2-like gene (VcMAF2), a MADS-AFFECTING FLOWERING 5-like gene (VcMAF5), and a VERNALIZATION1-like gene (VcVRN1), may function as integrators in place of FLOWERING LOCUS C (FLC) in the vernalization pathway. Because no CONSTAN1-like or FLOWERING LOCUS C-like genes were found in blueberry, VcCOL5 and VcMAF2/VcMAF5 or VRN1 might be the major integrator(s) in the photoperiod- and vernalization-mediated flowering pathway, respectively. The major down-stream genes of VcFT, i.e., SUPPRESSOR of Overexpression of Constans 1 like (VcSOC1), LEAFY-like (VcLFY), APETALA1-like (VcAP1), CAULIFLOWER 1-like (VcCAL1), and FRUITFULL-like (VcFUL) genes were present and showed high similarity to their orthologues in herbaceous plants. Moreover, overexpression of VcFT promoted expression of all of these VcFT downstream genes. These results suggest that VcFT's down-stream genes appear conserved in blueberry. PMID- 27271295 TI - Extensive sequencing of seven human genomes to characterize benchmark reference materials. AB - The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry. The data come from 12 technologies: BioNano Genomics, Complete Genomics paired-end and LFR, Ion Proton exome, Oxford Nanopore, Pacific Biosciences, SOLiD, 10X Genomics GemCode WGS, and Illumina exome and WGS paired-end, mate-pair, and synthetic long reads. Cell lines, DNA, and data from these individuals are publicly available. Therefore, we expect these data to be useful for revealing novel information about the human genome and improving sequencing technologies, SNP, indel, and structural variant calling, and de novo assembly. PMID- 27271297 TI - Interlaboratory evaluation of the assessment of arsenic bioaccumulation from field collected sediments using Hexagenia spp. AB - Standardized bioaccumulation testing of aquatic organisms is essential to understanding the impact of historical contamination on the quality of water and sediment. A standardized 28-d laboratory bioaccumulation method with a freshwater burrowing mayfly, Hexagenia spp., has been developed and internally validated by the Ontario Ministry of the Environment and Climate Change (MOECC). An interlaboratory comparison was conducted to assess the precision of this method. Field-collected sediment contaminated with arsenic was chosen for the present study. Control and test sediments were subsampled and sent to 6 laboratories to perform the bioaccumulation test. One laboratory failed to meet the control survival criterion of >=80%. When results of this laboratory are removed from the arsenic accumulation assessment, the mean interlaboratory variability (expressed as coefficient of variation) of the arsenic whole-body concentration is reduced from 44% to 24% in the test sediment-exposed Hexagenia spp. There was no significant interlaboratory difference between the Hexagenia spp. arsenic accumulations. While improved culturing and organism holding guidance may increase laboratory success, the MOECC Hexagenia spp. bioaccumulation test method has tight biological method precision when the control survival criterion is met. Environ Toxicol Chem 2016;35:2448-2455. (c) 2016 SETAC. PMID- 27271298 TI - USP6 gene rearrangement in nodular fasciitis and histological mimics. AB - AIMS: Nodular fasciitis is known to be a benign mimic of sarcoma, both clinically and histologically. Accurate diagnosis, particularly on small biopsies, remains a challenge, as the morphology can be varied and the immunophenotype is essentially non-specific. Recently, rearrangement of the ubiquitin-specific protease 6 (USP6) gene has been reported as a recurrent and specific finding in nodular fasciitis. The aim of this this study was to evaluate the diagnostic utility of USP6 fluorescence in-situ hybridization (FISH) analysis in a subset of spindle-cell proliferations in which nodular fasciitis enters into the differential diagnosis. METHODS AND RESULTS: A database search was performed at the Middlemore Hospital Histopathology Department. All in-house cases diagnosed between 2002 and March 2014 in which nodular fasciitis was considered as a differential diagnosis were retrospectively identified. Twenty cases were retrieved, reviewed and categorized as 'definite', 'possible' or 'definitely not' nodular fasciitis by consensus morphological opinion of three experienced pathologists. FISH analysis for USP6 rearrangement was performed in each case, with a commercially available break apart probe. Of seven cases that were morphologically categorized as 'definite' nodular fasciitis, six were FISH-positive and one was FISH-negative. Of four cases categorized as 'possible' nodular fasciitis, one was FISH-positive and three were FISH-negative. Nine cases categorized as 'definitely not' nodular fasciitis were all FISH-negative. In the morphologically definitive cases, FISH analysis for USP6 had a sensitivity of 86% and specificity of 100% for a diagnosis of nodular fasciitis. The positive predictive value was 100%, and the negative predictive value 90%. CONCLUSIONS: USP6 FISH is a useful ancillary test in cases where nodular fasciitis is a potential diagnostic consideration. PMID- 27271299 TI - Neurologic Immune-Related Adverse Events in Oncology Care. PMID- 27271300 TI - Correction: Escherichia coli DnaE Polymerase Couples Pyrophosphatase Activity to DNA Replication. AB - [This corrects the article DOI: 10.1371/journal.pone.0152915.]. PMID- 27271301 TI - Dry Olive Leaf Extract in Combination with Methotrexate Reduces Cell Damage in Early Rheumatoid Arthritis Patients-A Pilot Study. AB - The effects of co-administration of dry olive leaf extract (DOLE) with standard methotrexate (MTX) therapy on the parameters of cell damage and inflammation in patients with early and long-term rheumatoid arthritis (RA) were evaluated at baseline, 3 and 6 weeks. Patients were assigned to groups: the early phase RA group on MTX monotherapy (E MTX), and the two RA groups that received co treatment with DOLE and MTX: early (E MTX + DOLE) and long-term phase patients (L t MTX+ DOLE). Baseline values indicated increased parameters of cell damage and disruption of redox balance in all groups. After three weeks the E MTX + DOLE group maintained high catalase activity, exhibited decrease of lipid peroxidation and protein damage indicators-thiols and nitrites, while levels of DNA damage and pro-inflammatory interleukin-6 were significantly reduced. In E MTX group catalase activity remained unaltered while significant lipid peroxidation and DNA damage reductions were seen only after six weeks. L-t MTX + DOLE group showed only modest alterations of cell damage parameters during six weeks. Combined administration of DOLE with MTX contributes to faster reduction of cell damage, restores oxidative balance and improves interleukin-6 suppression during high disease activity in early phase RA, but not in long term patients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271303 TI - Primate genotyping via high resolution melt analysis: rapid and reliable identification of color vision status in wild lemurs. AB - Analyses of genetic polymorphisms can aid our understanding of intra- and interspecific variation in primate sociality, ecology, and behavior. Studies of primate opsin genes are prime examples of this, as single nucleotide variants (SNVs) in the X-linked opsin gene underlie variation in color vision. For primate species with polymorphic trichromacy, genotyping opsin SNVs can generally indicate whether individual primates are red-green color-blind (denoted homozygous M or homozygous L) or have full trichromatic color vision (heterozygous ML). Given the potential influence of color vision on behavior and fitness, characterizing the color vision status of study subjects is becoming commonplace for many primate field projects. Such studies traditionally involve a multi-step sequencing-based method that can be costly and time-consuming. Here we present a new reliable, rapid, and relatively inexpensive method for characterizing color vision in primate populations using high resolution melt analysis (HRMA). Using lemurs as a case study, we characterized variation at exons 3 and/or 5 of the X-linked opsin gene for 87 individuals representing nine species. We scored opsin genotypes and color vision status using both traditional sequencing-based methods as well as our novel melting-curve based HRMA protocol. For each species, the melting curves of varying genotypes (homozygous M, homozygous L, heterozygous ML) differed in melting temperature and/or shape. Melting curves for each sample were consistent across replicates, and genotype specific melting curves were consistent across DNA sources (blood vs. feces). We show that opsin genotypes can be quickly and reliably scored using HRMA once lab specific reference curves have been developed based on known genotypes. Although the protocol presented here focuses on genotyping lemur opsin loci, we also consider the larger potential for applying this approach to various types of genetic studies of primate populations. PMID- 27271304 TI - Physics of pure and non-pure positron emitters for PET: a review and a discussion. AB - With the increased interest in new PET tracers, gene-targeted therapy, immunoPET, and theranostics, other radioisotopes will be increasingly used in clinical PET scanners, in addition to (18)F. Some of the most interesting radioisotopes with prospective use in the new fields are not pure short-range beta(+) emitters but can be associated with gamma emissions in coincidence with the annihilation radiation (prompt gamma), gamma-gamma cascades, intense Bremsstrahlung radiation, high-energy positrons that may escape out of the patient skin, and high-energy gamma rays that result in some e (+)/e (-) pair production. The high level of sophistication in data correction and excellent quantitative accuracy that has been reached for (18)F in recent years can be questioned by these effects. In this work, we review the physics and the scientific literature and evaluate the effect of these additional phenomena on the PET data for each of a series of radioisotopes: (11)C, (13)N, (15)O, (18)F, (64)Cu, (68)Ga, (76)Br, (82)Rb, (86)Y, (89)Zr, (90)Y, and (124)I. In particular, we discuss the present complications arising from the prompt gammas, and we review the scientific literature on prompt gamma correction. For some of the radioisotopes considered in this work, prompt gamma correction is definitely needed to assure acceptable image quality, and several approaches have been proposed in recent years. Bremsstrahlung photons and (176)Lu background were also evaluated. PMID- 27271305 TI - Single-Nucleotide Polymorphisms and Markers of Oxidative Stress in Healthy Women. AB - PURPOSE: There is accumulating evidence that oxidative stress is an important contributor to carcinogenesis. We hypothesized that genetic variation in genes involved in maintaining antioxidant/oxidant balance would be associated with overall oxidative stress. METHODS: We examined associations between single nucleotide polymorphisms (SNPs) in MnSOD, GSTP1, GSTM1, GPX1, GPX3, and CAT genes and thiobarbituric acid-reactive substances (TBARS), a blood biomarker of oxidative damage, in healthy white women randomly selected from Western New York (n = 1402). We used general linear models to calculate age-adjusted geometric means of TBARS across the variants. We also examined the associations within strata of menopausal status. RESULTS: For MnSOD, being heterozygous was associated with lower geometric means of TBARS (less oxidative stress), 1.28 mg/dL, compared to homozygous T-allele or homozygous C-allele,1.35 mg/dL, and 1.31 mg/dL correspondingly (p for trend = 0.01). This difference remained among postmenopausal women, 1.40 mg/dL for TT, 1.32 mg/dL for TC, and 1.34mg/dL for CC (p for trend 0.015); it was attenuated among premenopausal women. SNPs in the other genes examined (GSTP1, GSTM1, GPX1, GPX3, and CAT) were not associated with TBARS. CONCLUSIONS: Our findings suggest that genetic variation in MnSOD gene may be associated with oxidative status, particularly among postmenopausal women. PMID- 27271307 TI - Mind the Vein. PMID- 27271306 TI - Alcohol consumption is associated with DXA measurement of adiposity: the Pro Saude Study, Brazil. AB - PURPOSE: Evaluate the association between alcohol consumption and body adiposity. METHODS: We analyzed cross-sectional data from a longitudinal investigation (Pro Saude Study), comprising a sample of 514 civil servants of both sexes (35-64 years). Daily alcohol consumption (wine, beer, and other alcoholic drinks) over the previous 6 months was assessed via food frequency questionnaire and categorized as no doses, up to 1 dose, and >=1 dose. The total body mass, total fat mass (TFM), android fat mass (AFM), and gynoid fat mass (GFM) were measured via dual-energy X-ray absorptiometry. AFM (AFM%) and GFM (GFM%) were expressed as percentages relative to TFM. The ratio of AFM% and GFM% was calculated. Multiple linear regression analyses were performed after adjusting for age, calories not originating from alcohol, leisure-time physical activity and education. RESULTS: Among nondrinkers, 59 % were women, and the age range between 45 and 54 years was predominant (44.3 %); 63.7 % of the nondrinkers were overweight/obese. Among drinkers of 1 dose or more/day, 67 % were males aged between 45 and 54 years (43.7 %); 69.1 % were overweight/obese. Among men, the daily consumption of >=1 alcohol dose (13 g) was associated with an approximately 2 % (beta = 2.2, IC = 0.077; 4.303) adjusted for age, calories not originated from alcohol, leisure time physical activity and education, increase in TFM, compared to those who reported no alcohol consumption during the previous 6 months. This association was not observed among women. In both sexes, no associations were observed between alcohol consumption and the other evaluated parameters of adiposity. CONCLUSION: Among men only, daily consumption of >=1 alcohol dose was associated with increased adiposity, despite the relatively low average alcohol consumption in this study population. PMID- 27271308 TI - Adverse Impact of Sleep Restriction and Circadian Misalignment on Autonomic Function in Healthy Young Adults. AB - Insufficient sleep and circadian rhythm disturbances have been each associated with adverse cardiovascular outcomes in epidemiological studies, but experimental evidence for a causal link is scarce. The present study compares the impact of circadian misalignment (CM) to circadian alignment (CA) on human autonomic function using a nonrandomized parallel group design to achieve the same total sleep time in both conditions. After baseline assessments (3 days with 10-hour bedtimes), 26 healthy young adults were assigned to sleep restriction (SR; eight 5-hour bedtimes) with either fixed nocturnal bedtimes (CA; n=13) or bedtimes delayed by 8.5 hours on 4 of the 8 days (CM; n=13). Daytime ambulatory blood pressure and heart rate (HR; CA, n=11; CM, n=10) and 24-hour urinary norepinephrine levels (CA, n=13; CM, n=13) were assessed at baseline and the end of SR. Nocturnal HR and HR variability were analyzed during sleep at baseline and during the fourth and seventh nights of SR (CA, n=8; CM, n=12). SR resulted in a significant increase in daytime HR in both groups, without changes in blood pressure. SR increased 24-hour urinary norepinephrine in the CM group (30+/-4 versus 21+/-2 MUg), but not in the circadian alignment group (group*condition, P=0.005). In contrast to the lack of detectable impact of CM on daytime autonomic function, SR with CM elicited greater increases in nocturnal HR, as well as greater reductions in vagal indices of HR variability, than SR without CM (group*condition, P<0.05). In conclusion, SR and CM both result in impaired autonomic function that could lead, under chronic conditions, to enhanced cardiovascular risk. PMID- 27271311 TI - Preface. PMID- 27271309 TI - Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study. AB - We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00*10(-4)) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13*10(-9)). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90*10(-12)) and LOC105369882 rs11104632 (P=4.51*10(-8)) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11*10(-22)) and mean arterial pressure (P=2.86*10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70*10( 7)), C2orf80 (P<1.00*10(-12)), EPHA6 (P=2.88*10(-7)), SCOC-AS1 (P=4.35*10(-14)), SCOC (P=6.46*10(-11)), CLGN (P=3.68*10(-13)), MGAT4D (P=4.73*10(-11)), ARHGAP42 (P<=1.00*10(-12)), CASP4 (P=1.31*10(-8)), and LINC01478 (P=6.75*10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium. PMID- 27271313 TI - Imaging fluorescence correlation spectroscopy studies of dye diffusion in self assembled organic nanotubes. AB - The rate and mechanism of diffusion by anionic sulforhodamine B (SRB) dye molecules within organic nanotubes self-assembled from bolaamphiphile surfactants were investigated by imaging fluorescence correlation spectroscopy (imaging-FCS). The inner and outer surfaces of the nanotubes are terminated with amine and glucose groups, respectively; the former allow for pH-dependent manipulation of nanotube surface charge while the latter enhance their biocompatibility. Wide field fluorescence video microscopy was used to locate and image dye-doped nanotubes dispersed on a glass surface. Imaging-FCS was then used to spatially resolve the SRB transport dynamics. Mobilization of the dye molecules was achieved by immersion of the nanotubes in buffer solution. Experiments were performed in pH 6.4, 7.4 and 8.4 buffers, at ionic strengths ranging from 1.73 mM to 520 mM. The results show that coulombic interactions between cationic ammonium ions on the inner nanotube surface and the anionic SRB molecules play a critical role in governing mass transport of the dye. The apparent dye diffusion coefficient, D, was found to generally increase with increasing ionic strength and with increasing pH. The D values obtained were found to be invariant along the nanotube length. Mass transport of the SRB molecules within the nanotubes is concluded to occur by a desorption-mediated Fickian diffusion mechanism in which dye motion is slowed by its coulombic interactions with the inner surfaces of the nanotubes. The results of these studies afford information essential to the use of organic nanotubes in controlled drug release applications. PMID- 27271310 TI - Efficacy of Servo-Controlled Splanchnic Venous Compression in the Treatment of Orthostatic Hypotension: A Randomized Comparison With Midodrine. AB - Splanchnic venous pooling is a major hemodynamic determinant of orthostatic hypotension, but is not specifically targeted by pressor agents, the mainstay of treatment. We developed an automated inflatable abdominal binder that provides sustained servo-controlled venous compression (40 mm Hg) and can be activated only on standing. We tested the efficacy of this device against placebo and compared it to midodrine in 19 autonomic failure patients randomized to receive either placebo, midodrine (2.5-10 mg), or placebo combined with binder on separate days in a single-blind, crossover study. Systolic blood pressure (SBP) was measured seated and standing before and 1-hour post medication; the binder was inflated immediately before standing. Only midodrine increased seated SBP (31+/-5 versus 9+/-4 placebo and 7+/-5 binder, P=0.003), whereas orthostatic tolerance (defined as area under the curve of upright SBP [AUCSBP]) improved similarly with binder and midodrine (AUCSBP, 195+/-35 and 197+/-41 versus 19+/-38 mm Hg*minute for placebo; P=0.003). Orthostatic symptom burden decreased with the binder (from 21.9+/-3.6 to 16.3+/-3.1, P=0.032) and midodrine (from 25.6+/-3.4 to 14.2+/-3.3, P<0.001), but not with placebo (from 19.6+/-3.5 to 20.1+/-3.3, P=0.756). We also compared the combination of midodrine and binder with midodrine alone. The combination produced a greater increase in orthostatic tolerance (AUCSBP, 326+/-65 versus 140+/-53 mm Hg*minute for midodrine alone; P=0.028, n=21) and decreased orthostatic symptoms (from 21.8+/-3.2 to 12.9+/-2.9, P<0.001). In conclusion, servo-controlled abdominal venous compression with an automated inflatable binder is as effective as midodrine, the standard of care, in the management of orthostatic hypotension. Combining both therapies produces greater improvement in orthostatic tolerance. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00223691. PMID- 27271312 TI - Mega clinical trials which have shaped the RAS intervention clinical practice. AB - Following extensive clinical research, drugs affecting the renin-angiotensin system have been used for the treatment of patients with congestive heart failure, myocardial infarction, hypertension, diabetic nephropathy, chronic renal failure and for reducing the risk of developing major cardiovascular (CV) events. This review examines all mega trials (those involving >1000 patients) and smaller pivotal trials involving angiotensin-converting enzyme inhibitors (ACE-Is; 25 mega trials) and angiotensin receptor blockers (ARBs; 27 mega trials) to provide perspective on the huge database of evidence that has accumulated on the use of these drugs. Our review demonstrates that ACE-Is and ARBs are generally as effective as conventional therapies in the treatment of hypertension, but offer additional cardioprotective benefits in patients with heart failure, and in those who have experienced myocardial infarction. Also, both ACE-Is and ARBs are capable of renal protection in addition to their blood-pressure-lowering effects. Although ACE-Is and ARBs provide major benefits to CV patients, doubts remain over the concept of blood-pressure-independent CV protection offered by both classes of drugs. ACE-Is and ARBs appear to be equally effective with respect to morbidity and mortality endpoints, but ARBs are better tolerated. Considering the available evidence, the combined use of an ACE-I and ARB should be avoided and full doses of either ACE-I or ARB should be aimed for as evidence suggests they provide a greater prognostic benefit. PMID- 27271315 TI - [Not Available]. PMID- 27271314 TI - Biologic interventions for fatigue in rheumatoid arthritis. AB - BACKGROUND: Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage. OBJECTIVES: To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis. SEARCH METHODS: We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors. SELECTION CRITERIA: We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure. DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model. MAIN RESULTS: We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti interferon gamma monoclonal antibody). All but two of the studies were double blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and 4682 participants in the control groups. Overall, quality of randomised controlled trials was moderate with a low to unclear risk of bias in the reporting of the outcome of fatigue. We downgraded the quality of the studies from high to moderate because of potential reporting bias (studies included post hoc analyses favouring reporting of positive result and did not always include all randomised individuals). Some studies recruited only participants with early disease. The studies used five different instruments to assess fatigue in these studies: the Functional Assessment of Chronic Illness Therapy Fatigue Domain (FACIT-F), Short Form-36 Vitality Domain (SF-36 VT), Visual Analogue Scale (VAS) (0 to 100 or 0 to 10) and the Numerical Rating Scale (NRS). We calculated standard mean differences for pooled data in meta-analyses. Overall treatment by biologic agents led to statistically significant reduction in fatigue with a standardised mean difference of -0.43 (95% confidence interval (CI) -0.38 to -0.49). This equates to a difference of 6.45 units (95% CI 5.7 to 7.35) of FACIT-F score (range 0 to 52). Both types of biologic agents achieved a similar level of improvement: for anti-TNF agents, this stood at -0.42 (95% CI 0.35 to -0.49), equivalent to 6.3 units (95% CI 5.3 to 7.4) on the FACIT-F score; and for non-anti-TNF agents, it was -0.46 (95% CI -0.39 to -0.53), equivalent to 6.9 units (95% CI 5.85 to 7.95) on the FACIT-F score. In most studies, the double blind period was 24 weeks or less. No study assessed long-term changes in fatigue. AUTHORS' CONCLUSIONS: Treatment with biologic interventions in patients with active RA can lead to a small to moderate improvement in fatigue. The magnitude of improvement is similar for anti-TNF and non-anti-TNF biologics. However, it is unclear whether the improvement results from a direct action of the biologics on fatigue or indirectly through reduction in inflammation, disease activity or some other mechanism. PMID- 27271316 TI - Composition and dynamics of the uterine NK cell KIR repertoire in menstrual blood. AB - Uterine natural killer (NK) cells are abundantly present in endometrium and decidua. Their function is governed by interactions between killer cell immunoglobulin-like receptors (KIRs) and cognate human leukocyte antigen (HLA) class I ligands. These interactions have implications for reproductive success. Whereas most uterine NK cells are known to express KIRs, little information is available about KIR repertoire formation and stability over time. This is primarily due to inherent difficulties in gaining access to human uterine tissue. As endometrial immune cells are shed during menstruation, menstrual blood may serve as a source for studies of KIRs on uterine NK cells. Here, we performed a combined assessment of six inhibitory and activating KIRs on uterine NK cells from paired menstrual and peripheral blood. Menstrual blood contained a high frequency of uterine NK cells expressing KIRs. The uterine NK cell KIR repertoires were markedly different from those in peripheral blood NK cells, biased toward KIR2D-receptor expression, and formed independently of selection conferred by cognate HLA class I molecules. Moreover, uterine NKG2C+self-KIR+ NK cell expansions were detected. Finally, the distinct KIR repertoires of uterine NK cells were stable over multiple menstrual cycles. Our results provide novel insight into KIR repertoire formation on human uterine NK cells. PMID- 27271317 TI - Vasoactive intestinal peptide dampens formyl-peptide-induced ROS production and inflammation by targeting a MAPK-p47phox phosphorylation pathway in monocytes. AB - Reactive oxygen species (ROS) produced by the phagocyte NADPH oxidase (NOX2) are required for microbial clearance; however, when produced in excess they exacerbate inflammatory response and injure surrounding tissues. NOX2 is a multicomponent enzyme composed of membrane-associated cytochrome b588 and cytosolic components p47phox, p67phox, p40phox, and rac1/2. We investigated whether vasoactive intestinal peptide (VIP), an endogenous immune-modulatory peptide, could affect ROS production by NOX2 in primary human phagocytes. VIP did not modulate basal ROS production by phagocytes, but it inhibited monocyte and not neutrophil ROS production in response to the bacterial peptide N-formyl methionyl-leucyl-phenylalanine (fMLF). The action of VIP was essentially mediated by high-affinity G-protein coupled receptors VPAC1 as its specific agonist, [ALA11,22,28]VIP, mimicked VIP-inhibitory effect, whereas the specific VPAC1 antagonist, PG97-269, blunted VIP action. Further, we showed that VIP inhibited fMLF-induced phosphorylation of ERK1/2 (extracellular signal-regulated kinase 1/2), p38MAPK (p38 mitogen-activated protein kinase) pathways, and phosphorylation of p47phox on Ser345 residue. Also, VIP exerted an anti inflammatory effect in a model of carrageenan-induced inflammation in rats. We thus found that VIP exerts anti-inflammatory effects by inhibiting the "MAPK p47phox phosphorylation-NOX2 activation" axis. These data suggest that VIP acts as a natural anti-inflammatory agent of the mucosal system and its analogs could be novel anti-inflammatory molecules. PMID- 27271318 TI - Gold nanoparticle-conjugated pepsin for efficient solution-like heterogeneous biocatalysis in analytical sample preparation protocols. AB - Immobilization of enzymes on mesoporous microparticulate carriers has traditionally been accompanied by reduction in enzyme activity. Herein, we document that immobilization of pepsin via amide coupling on gold nanoparticles (GNPs) with a carboxy-terminated hydrophilic PEG7 shell resulted in a heterogeneous nanobiocatalyst with essentially equivalent turnover rates, k cat (90 %), and enhanced catalytic efficiencies, k cat/K M (107 %), compared to homogeneous catalysis with pepsin in free solution for cytochrome C as model substrate. This heterogeneous catalyst showed further at least equivalent bioactivity in a digestion reaction of a protein mixture consisting of cytochrome C, bovine serum albumin, and myoglobin. UHPLC-ESI-QTOF-MS/MS analysis of the digests with subsequent Mascot database search allowed unequivocal identification of all proteins with high score and good sequence coverage. The functionalized nanoparticles were further characterized by Vis spectroscopy in terms of the surface plasmon resonance (SPR) band, by dynamic light scattering (DLS) with regard to hydrodynamic diameters, and in view of their zeta potentials at each step of synthesis and surface modification. These measurements also revealed that the pepsin-functionalized GNPs were sufficiently stable over at least 1 month; thus providing a satisfactory shelf life to the heterogeneous catalyst. Advantageously, the pepsin-GNP bioconjugate can be conveniently removed after reaction by simple centrifugation steps which makes them a useful tool for analysis of therapeutic peptides and proteins, including monoclonal antibodies. The practical utility of the nanobiocatalyst was documented by digestion of a monoclonal antibody which yielded the F(ab')2 fragment with a mass of 97,619.4 Da. Graphical Abstract Pepsin conjugated to pegylated gold nanoparticles exhibit properties of homogeneous catalysis such as enzyme activity like pepsin in solution and ability to pipette the stable colloidal suspension whereas one can take benefit from easy removal by centrifugation and re-use which are characteristics of heterogeneous catalysis. PMID- 27271319 TI - Development of an on-site rapid real-time polymerase chain reaction system and the characterization of suitable DNA polymerases for TaqMan probe technology. AB - On-site quantitative analyses of microorganisms (including viruses) by the polymerase chain reaction (PCR) system are significantly influencing medical and biological research. We have developed a remarkably rapid and portable real-time PCR system that is based on microfluidic approaches. Real-time PCR using TaqMan probes consists of a complex reaction. Therefore, in a rapid real-time PCR, the optimum DNA polymerase must be estimated by using actual real-time PCR conditions. In this study, we compared the performance of three DNA polymerases in actual PCR conditions using our rapid real-time PCR system. Although KAPA2G Fast HS DNA Polymerase has the highest enzymatic activity among them, SpeedSTAR HS DNA Polymerase exhibited better performance to rapidly increase the fluorescence signal in an actual real-time PCR using TaqMan probes. Furthermore, we achieved rapid detection of Escherichia coli in 7 min by using SpeedSTAR HS DNA Polymerase with the same sensitivity as that of a conventional thermal cycler. PMID- 27271320 TI - Effect of temperature (5-25 degrees C) on epiphytic lactic acid bacteria populations and fermentation of whole-plant corn silage. AB - AIMS: The objective of this study was to investigate the effect of temperature (5 25 degrees C) on epiphytic lactic acid bacteria (LAB) populations during 60 days of fermentation of whole-plant corn silage. METHODS AND RESULTS: Vacuum bag mini silos of chopped whole-plant corn were incubated at five different temperatures (5, 10, 15, 20 and 25 degrees C), according to a completely randomized design with four repetitions. The silos were opened and sampled on day 0, 1, 2, 3, 7, 28 and 60. At 20 and 25 degrees C, Lactobacillus plantarum- and Pediococcus pentosaceus-related operational taxonomic units (OTU) dominated the fermentation within 1 day. After 7 days, the OTU related to the heterofermentative species Lactobacillus buchneri began to appear and it eventually dominated silages incubated at these temperatures. Population dynamic of LAB at 5 and 10 degrees C was different. At these temperatures, Leuconostoc citreum OTU was identified at the beginning of the fermentation. Thereafter, Lactobacillus sakei- and Lactobacillus curvatus-related OTU appeared and quickly prevailed. Corn silage at 15 degrees C acted as a transition between 20-25 degrees C and 5-10 degrees C, in terms of LAB diversity and succession. CONCLUSION: The conditions of silage incubation temperature affect species diversity of LAB population with notable difference along the temperature gradient. Colder temperature conditions (5 and 10 degrees C) have led to the identification of LAB species never observed in corn silage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the impact of temperature gradient on the diversity and some important population shift of lactic acid bacteria communities during fermentation of corn silage. PMID- 27271322 TI - Dispensable chromosomes in Fusarium oxysporum f. sp. lycopersici. AB - The genomes of many filamentous fungi consist of a 'core' part containing conserved genes essential for normal development as well as conditionally dispensable (CD) or lineage-specific (LS) chromosomes. In the plant-pathogenic fungus Fusarium oxysporum f. sp. lycopersici, one LS chromosome harbours effector genes that contribute to pathogenicity. We employed flow cytometry to select for events of spontaneous (partial) loss of either the two smallest LS chromosomes or two different core chromosomes. We determined the rate of spontaneous loss of the 'effector' LS chromosome in vitro at around 1 in 35 000 spores. In addition, a viable strain was obtained lacking chromosome 12, which is considered to be a part of the core genome. We also isolated strains carrying approximately 1-Mb deletions in the LS chromosomes and in the dispensable core chromosome. The large core chromosome 1 was never observed to sustain deletions over 200 kb. Whole genome sequencing revealed that some of the sites at which the deletions occurred were the same in several independent strains obtained for the two chromosomes tested, indicating the existence of deletion hotspots. For the core chromosome, this deletion hotspot was the site of insertion of the marker used to select for loss events. Loss of the core chromosome did not affect pathogenicity, whereas loss of the effector chromosome led to a complete loss of pathogenicity. PMID- 27271321 TI - Integrated Computational Solution for Predicting Skin Sensitization Potential of Molecules. AB - INTRODUCTION: Skin sensitization forms a major toxicological endpoint for dermatology and cosmetic products. Recent ban on animal testing for cosmetics demands for alternative methods. We developed an integrated computational solution (SkinSense) that offers a robust solution and addresses the limitations of existing computational tools i.e. high false positive rate and/or limited coverage. RESULTS: The key components of our solution include: QSAR models selected from a combinatorial set, similarity information and literature-derived sub-structure patterns of known skin protein reactive groups. Its prediction performance on a challenge set of molecules showed accuracy = 75.32%, CCR = 74.36%, sensitivity = 70.00% and specificity = 78.72%, which is better than several existing tools including VEGA (accuracy = 45.00% and CCR = 54.17% with 'High' reliability scoring), DEREK (accuracy = 72.73% and CCR = 71.44%) and TOPKAT (accuracy = 60.00% and CCR = 61.67%). Although, TIMES-SS showed higher predictive power (accuracy = 90.00% and CCR = 92.86%), the coverage was very low (only 10 out of 77 molecules were predicted reliably). CONCLUSIONS: Owing to improved prediction performance and coverage, our solution can serve as a useful expert system towards Integrated Approaches to Testing and Assessment for skin sensitization. It would be invaluable to cosmetic/ dermatology industry for pre screening their molecules, and reducing time, cost and animal testing. PMID- 27271324 TI - Chiral HPLC Separation, Absolute Structural Elucidation, and Determination of Stereochemical Stability of trans-Bis[2-(2-pyridinyl)aminophenolato] Cyclotriphosphazene. AB - Chiral high-performance liquid chromatography (HPLC) separation of trans-bis[2-(2 pyridyl)aminophenolato] dichlorocyclotriphosphazene was achieved and the absolute configuration of was assigned to be S,S by single-crystal X-ray structural analysis. The optically pure 1,2-diphenyl-1,2-ethanediolate derivatives (+)- and (-)- were synthesized by the reactions of and with (R,R)-hydrobenzoin, respectively, in refluxing toluene in the presence of an excess amount of triethylamine and a catalytic amount of 4-(dimethylamino)pyridine. The racemization of the enantiomers of and the epimerization of diastereomers of 2 were not observed in refluxing toluene neither under acidic nor basic conditions. The stereochemistry of was confirmed by the crystal structure of (+)- and bis[(4 methyl-2-pyridyl)oxy]cyclotriphosphazene derived from . Chirality 28:556-561, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27271323 TI - Melatonin Inhibits CXCL10 and MMP-1 Production in IL-1beta-Stimulated Human Periodontal Ligament Cells. AB - Melatonin is a hormone that is mainly secreted by the pineal gland and exhibits a wide spectrum of activities, including antioxidant functions. Melatonin has been detected in gingival crevicular fluid. However, the role of melatonin in periodontal tissue is still uncertain. The aim of this study was to examine the effects of melatonin on inflammatory mediator expression in human periodontal ligament cells (HPDLC). Interleukin (IL)-1beta induced CXC chemokine ligand (CXCL)10, matrix metalloproteinase (MMP)-1, and tissue inhibitors of metalloproteinase (TIMP)-1 production in HPDLC. Melatonin decreased CXCL10 and MMP-1 production and increased TIMP-1 production in IL-1beta-stimulated HPDLC. Western blot analysis showed that melatonin inhibited p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK) phosphorylation, and IkB alpha degradation and phosphorylation in IL-1beta-stimulated HPDLC. These results suggest that melatonin might inhibit Th1 cell migration by reducing CXCL10 production. Moreover, melatonin might inhibit soft tissue destruction by decreasing MMP-1 production in periodontal lesions. PMID- 27271325 TI - [Percutaneous sclerotherapy with polidocanol : Successful relapse therapy of infantile aneurysmal bone cyst]. AB - The aneurysmal bone cyst (ABC) is well-known for its local expansile growth form and for the high risk of recurrence after treatment. We present the case of a 6 year-old patient with a large ABC in the metaphysis of the proximal tibia, which showed recurrence only five months after treatment with curettage and autologous bone graft. By using six percutaneous intralesional injections of polidocanol the patient was successfully treated with no recurrence. After 18 months, a mild genu valgum was clinically noted. PMID- 27271326 TI - [Outcome in traumatic brain injury : Considered from a neurological viewpoint]. AB - BACKGROUND: There are many studies on the prognosis and mortality for the acute care of traumatic brain injury (TBI) during the first year. Prediction of the long-term outcome after TBI is more difficult, and can be ascribed to indistinct methods and the necessity of taking into account multiple influencing factors. OBJECTIVE: The main factors that determine the long-term outcome of TBI are described. MATERIALS AND METHODES: A summary of the relevant literature and experience of the reintegration of TBI patients are presented. RESULTS: The major factors predicting the long-term outcome of TBI are well-known. They can be measured by International Classification of Functioning, Disability and Health (ICF) of the World Health Organization and self-reported quality of life, which are important for the prognosis. Returning to work has a particularly positive effect on the quality of life. CONCLUSIONS: Environmental factors are most predictive of long-term TBI outcome. The awareness of the interaction of all these factors requires a individualized long-term rehabilitation. PMID- 27271328 TI - PCI-24781 can improve in vitro and in vivo developmental capacity of pig somatic cell nuclear transfer embryos. AB - OBJECTIVE: To examine the effect of PCI-24781 (abexinostat) on the blastocyst formation rate in pig somatic cell nuclear transferred (SCNT) embryos and acetylation levels of the histone H3 lysine 9 and histone H4 lysine 12. RESULTS: Treatment with 0.5 nM PCI-24781 for 6 h significantly improved the development of cloned embryos, in comparison to the control group (25.3 vs. 10.5 %, P < 0.05). Furthermore, PCI-24781 treatment led to elevated acetylation of H3K9 and H4K12. TUNEL assay and Hoechst 33342 staining revealed that the percentage of apoptotic cells in blastocysts was significantly lower in PCI-24781-treated SCNT embryos than in untreated embryos. Also, PCI-24781-treated embryos were transferred into three surrogate sows, one of whom became pregnant and two fetuses developed. CONCLUSION: PCI-24781 improves nuclear reprogramming and the developmental potential of pig SCNT embryos. PMID- 27271327 TI - Vitamin C alleviates aging defects in a stem cell model for Werner syndrome. AB - Werner syndrome (WS) is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, telomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN-deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS. PMID- 27271329 TI - Risk Factors for Local Recurrence of Large, Flat Colorectal Polyps after Endoscopic Mucosal Resection. AB - AIMS: Removal of large, flat colorectal polyps by endoscopic mucosal resection (EMR) is effective, but local recurrences occur regularly. This study investigated risk factors for local recurrence. METHOD: Cases of EMR of flat colorectal polyps >=20 mm at an academic center from 2004 to 2011 were retrospectively analyzed for polyp features, resection technique, complications and local recurrences. Behavioral risk factors were retrospectively determined by self-administered questionnaires. RESULTS: Data were collected for 129 patients (57.3% male, mean age at time of EMR: 65.0 years). Mean polyp size was 37.2 mm. Polyps were mostly adenoma with low-grade dysplasia (58.1%) and predominantly located in the right colon (62%). En bloc resection was performed in 31.8%. The median follow-up time was 40 months. Local recurrence occurred in 26.3% of patients, with 87% being recurrence-free after 1 year (95% CI 81-93%). A history of smoking was reported by 51.6% of patients and 88.4% reported regular alcohol consumption. Univariate analysis showed that polyp size and piecemeal resection were associated with risk of local recurrence. In multivariate analysis, only polyp size was predictive for local recurrence. No association was found for behavioral risk factors. CONCLUSION: Polyp size is the main predictor of local recurrence after EMR of large, flat colorectal polyps. PMID- 27271330 TI - Numerical research on the anisotropic transport of thermal neutron in heterogeneous porous media with micron X-ray computed tomography. AB - The anisotropic transport of thermal neutron in heterogeneous porous media is of great research interests in many fields. In this paper, it is the first time that a new model based on micron X-ray computed tomography (CT) has been proposed to simultaneously consider both the separation of matrix and pore and the distribution of mineral components. We apply the Monte Carlo method to simulate thermal neutrons transporting through the model along different directions, and meanwhile detect those unreacted thermal neutrons by an array detector on the other side of the model. Therefore, the anisotropy of pore structure can be imaged by the amount of received thermal neutrons, due to the difference of rock matrix and pore-filling fluids in the macroscopic reaction cross section (MRCS). The new model has been verified by the consistent between the simulated data and the pore distribution from X-ray CT. The results show that the evaluation of porosity can be affected by the anisotropy of media. Based on the research, a new formula is developed to describe the correlation between the resolution of array detectors and the quality of imaging. The formula can be further used to analyze the critical resolution and the suitable number of thermal neutrons emitted in each simulation. Unconventionally, we find that a higher resolution cannot always lead to a better image. PMID- 27271332 TI - Letter to the Editor: A discussion on the benefits of radiological food guidelines under normal conditions. PMID- 27271331 TI - DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional alpha thalassaemia. AB - Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional alpha-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable alpha-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-alpha(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Pakse (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional alpha-thalassaemia mutations. Duplex-PCR was used to confirm Hb Pakse and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (alpha(codon 59)alpha/alpha(CS)alpha) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Pakse for the first time in a Malaysian patient (alpha(codon 59)alpha/alpha(Pakse)alpha) after nine years of being misdiagnosis with Hb Adana and HbCS (alpha(codon 59)alpha/alpha(CS)alpha). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations. PMID- 27271333 TI - Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells. AB - Betulin, an abundant natural compound, significantly inhibited the cell viability of advanced human gastric cancer SGC7901 cells. Mechanism study demonstrated that betulin induced apoptosis through mitochondrial Bax and Bak accumulation-mediated intrinsic apoptosis pathway. Downregulation of the anti-apoptosis proteins Bcl-2 and XIAP was involved during betulin-induced cell apoptosis. Reactive oxygen species (ROS) was generated in cells after betulin treatment in a time- and dose dependent manner. Addition of antioxidant N-acetyl-L-cysteine (NAC) significantly attenuated betulin-induced ROS generation as well as Bcl-2 and XIAP downregulation. The mitochondrial accumulation of Bax and Bak, as well as caspase activity, was also remarkably inhibited by NAC treatment, indicating that ROS are important signaling intermediates that lead to betulin-induced apoptosis by modulating multiple apoptosis-regulating proteins in SGC7901 cells. PMID- 27271334 TI - Timosaponin AIII induces apoptosis and autophagy in human melanoma A375-S2 cells. AB - Timosaponin AIII (AIII), a steroidal saponin isolated from Anemarrhena asphodeloides Bge. Our study showed that AIII induced both apoptosis and autophagy, and autophagy inhibited apoptosis in A375S2 cells. Furtherly, this study was carried out to investigate what kind of cytokines plays an important role in this process. The results revealed that AIII induced apoptosis through activating c-Jun N-terminal protein kinase (JNK) or extracellular signal related kinase (ERK) signaling pathway and generating NO. However, JNK or ERK inhibited autophagy, while NO had no effect on autophagy. Therefore, JNK, ERK or NO regulates two programmed death processes in different ways. AIII did not show obvious cytotoxic effect on human peripheral blood mononuclear cells, which indicated that AIII has less side effects on normal cells, and could be considered as a leading compound for developing novel anticancer drug. PMID- 27271336 TI - Correction: Time Slices: What Is the Duration of a Percept? AB - [This corrects the article DOI: 10.1371/journal.pbio.1002433.]. PMID- 27271335 TI - The Mystery of Antibodies Against Polyethylene Glycol (PEG) - What do we Know? AB - PURPOSE: Recent findings demonstrated anti-PEG antibody formation in some healthy individuals and patients who have not received PEGylated biotherapeutics. Some of these findings evoked criticism because of shortcomings in the antibody assays used. To better understand this topic, we established robust antibody analytics and screened two cohorts of healthy individuals and one cohort of hemophilia patients for the expression of anti-PEG antibodies. METHODS: A flow cytometry approach and a fully validated ELISA platform were established to detect specific anti-PEG antibodies. Immunohistochemistry was used to test for potential binding of anti-PEG antibodies to human tissues. RESULTS: IgM and/or IgG anti-PEG antibodies are expressed by some healthy individuals and by some patients with hemophilia who have not received PEGylated biotherapeutics. These antibodies can be either transient or persistent and recognize PEGs of different sizes with or without terminal methoxy groups. Age and location of healthy individuals influence the prevalence of IgG but not of IgM antibodies. Anti-PEG antibodies do not cross-react with human tissues supporting the safety of the antibodies. CONCLUSION: We confirm that some healthy individuals and some patients with hemophilia express specific antibodies against PEG which are not associated with any pathology and do not bind to human tissues. PMID- 27271337 TI - Diels-Alder attachment of a planar organic molecule to a dangling bond dimer on a hydrogenated semiconductor surface. AB - Construction of single-molecule electronic devices requires the controlled manipulation of organic molecules and their properties. This could be achieved by tuning the interaction between the molecule and individual atoms by local "on surface" chemistry, i.e., the controlled formation of chemical bonds between the species. We demonstrate here the reversible attachment of a planar conjugated polyaromatic molecule to a pair of unpassivated dangling bonds on a hydrogenated Ge(001):H surface via a Diels-Alder [4+2] addition using the tip of a scanning tunneling microscope (STM). Due to the small stability difference between the covalently bonded and a nearly undistorted structure attached to the dangling bond dimer by long-range dispersive forces, we show that at cryogenic temperatures the molecule can be switched between both configurations. The reversibility of this covalent bond forming reaction may be applied in the construction of complex circuits containing organic molecules with tunable properties. PMID- 27271338 TI - LCD Monitors as an Alternative for Precision Demanding Visual Psychophysical Experiments. AB - Precise timing and presentation of stimuli is critical in vision research, still, the limiting factor in successful recognition is often the monitor itself that is used to present the stimuli. The most widespread method is the use of monitors controlled by personal computers. Traditionally, most experiments used cathode ray tubes but they are more and more difficult to access, and instead, liquid crystal displays are getting more and more popular. The two types have fundamentally different working principles and limitations in displaying the stimulus.In our experiments, the temporal precision of the stimulus presentation was in focus. We investigated whether liquid-crystal displays, which are not considered to be fit to display fast successive stimuli, can represent an alternative choice for cathode-ray tubes. We used the double flash and the flicker illusion to compare the technical capabilities of the two monitor types. These illusions not only do require a precise timing but also a very short exposure to the stimuli. At the same time, the interstimulus interval is also of extreme importance. In addition, these illusions require peripheral stimulation of the retina, which is more sensitive to the temporal aspects of the visual stimulus. On the basis of previous studies and our own psychophysical results, we suggest that liquid-crystal displays might be a good alternative for precise, frame-to-frame stimulus presentation even if parts of the stimuli are projected on the peripheral retina. PMID- 27271339 TI - A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia. AB - Episodic ataxia type 1 (EA1) is an autosomal dominant channelopathy caused by mutations in KCNA1, which encodes the voltage-gated potassium channel, Kv1.1. Eleven members of an EA family were evaluated with molecular and functional studies. A novel c.746T>G (p.Phe249Cys) missense mutation of KCNA1 segregated in the family members with episodic ataxia, myokymia, and malignant hyperthermia susceptibility. No mutations were found in the known malignant hyperthermia genes RYR1 or CACNA1S. The Phe249Cys-Kv1.1 channels did not show any currents upon functional expression, confirming a pathogenic role of the mutation. Malignant hyperthermia may be a presentation of KCNA1 mutations, which has significant implications for the clinical care of these patients and illustrates the phenotypic heterogeneity of KCNA1 mutations. PMID- 27271340 TI - Advanced Glycation End Product (AGE) Accumulation in the Skin is Associated with Depression: The Maastricht Study. AB - BACKGROUND: Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression. METHODS: Cross-sectional data were used from the Maastricht Study (N = 862, mean age 59.8 +/- 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein bound pentosidine were measured with high-performance liquid chromatography and fluorescence detection. Nepsilon-(carboxymethyl)lysine (CML) and Nepsilon (carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine-item Patient Health Questionnaire and the Mini International Neuropsychiatric Interview. RESULTS: Higher SAF was associated with depressive symptoms (beta = 0.42, 95% CI 0.12-0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04-1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder. CONCLUSIONS: This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression. PMID- 27271341 TI - Cerebral function monitoring on a general paediatric ward: feasibility and potential. AB - Cerebral function monitoring is widely used in neonatal intensive care, but its potential role in assessment of older infants is scarcely reported. We reviewed the use of cerebral function monitoring on a general paediatric ward in a series of young infants admitted with abnormal movements. Review of the amplitude integrated EEG obtained by cerebral function monitoring revealed electrographic seizures in four of seven infants monitored. We also surveyed general paediatric wards in hospitals in our region of the UK to ask about current use of cerebral function monitoring and local availability of formal electroencephalography services. Cerebral function monitoring was not being used in the 16 other paediatric departments surveyed, and there was very limited provision for obtaining a full-array electroencephalogram out-of-hours. CONCLUSION: With adequate training and education, it is feasible to undertake cerebral function monitoring on a general paediatric ward. Continuous cerebral function monitoring is a tool that has potential use for detecting clinical seizures and augmenting clinical neuro-observations of young children admitted to a general paediatric ward. WHAT IS KNOWN: * In intensive care settings, cerebral function monitoring (CFM) has long been used for the continuous bedside monitoring of brain function in critically ill neonates, children and adults. * Very few studies have looked at the use of CFM outside of the intensive care setting, and it is presently unclear if CFM is used in the general paediatric ward. What is new: * CFM is presently not widely used in the general paediatric setting. * With appropriate training and support, CFM can be successfully introduced to the general paediatric ward with the potential to enhance the clinical monitoring of young infants admitted with abnormal movements. PMID- 27271342 TI - Social Support and Exclusive Breast feeding among Canadian Women. AB - BACKGROUND: The World Health Organization recommendation for exclusive breast feeding for 6 months has been endorsed by Health Canada, the Canadian Pediatric Society, Dietitians of Canada, and the Breastfeeding Committee for Canada as of 2012. This study examines whether social support is associated with exclusive breast feeding up to 6 months among Canadian mothers. METHODS: We utilised data from the Canadian Community Health Survey and limited our sample to mothers who gave birth in the 5 years prior to the 2009-2010 survey (n = 2133). Multivariable logistic regression was used to examine the relationship between exclusive breast feeding and four dimensions of social support: (i) tangible, (ii) affectionate, (iii) positive social interaction, and (iv) emotional and informational, based on the Medical Outcomes Study Social Support Scale. Absolute and relative differences in the probability of breast feeding exclusively and their 95% confidence intervals were calculated. RESULTS: In adjusted models, differences in the probability of exclusive breast feeding for 6 months were not different among women with high vs. low social support. The association between social support and breastfeeding exclusively was modified by education level, with significantly higher probability of breast feeding exclusively among women with lower education and high vs. low levels of tangible and affectionate support. CONCLUSIONS: Among women with education below a high school level, high tangible and affectionate support significantly increased probability of exclusive breast feeding for 6 months in this study. Efforts to encourage exclusive breast feeding need to address social support for mothers, especially those with lower education. PMID- 27271343 TI - AGIA Tag System Based on a High Affinity Rabbit Monoclonal Antibody against Human Dopamine Receptor D1 for Protein Analysis. AB - Polypeptide tag technology is widely used for protein detection and affinity purification. It consists of two fundamental elements: a peptide sequence and a binder which specifically binds to the peptide tag. In many tag systems, antibodies have been used as binder due to their high affinity and specificity. Recently, we obtained clone Ra48, a high-affinity rabbit monoclonal antibody (mAb) against dopamine receptor D1 (DRD1). Here, we report a novel tag system composed of Ra48 antibody and its epitope sequence. Using a deletion assay, we identified EEAAGIARP in the C-terminal region of DRD1 as the minimal epitope of Ra48 mAb, and we named this sequence the "AGIA" tag, based on its central sequence. The tag sequence does not include the four amino acids, Ser, Thr, Tyr, or Lys, which are susceptible to post-translational modification. We demonstrated performance of this new tag system in biochemical and cell biology applications. SPR analysis demonstrated that the affinity of the Ra48 mAb to the AGIA tag was 4.90 * 10-9 M. AGIA tag showed remarkably high sensitivity and specificity in immunoblotting. A number of AGIA-fused proteins overexpressed in animal and plant cells were detected by anti-AGIA antibody in immunoblotting and immunostaining with low background, and were immunoprecipitated efficiently. Furthermore, a single amino acid substitution of the second Glu to Asp (AGIA/E2D) enabled competitive dissociation of AGIA/E2D-tagged protein by adding wild-type AGIA peptide. It enabled one-step purification of AGIA/E2D-tagged recombinant proteins by peptide competition under physiological conditions. The sensitivity and specificity of the AGIA system makes it suitable for use in multiple methods for protein analysis. PMID- 27271345 TI - Specific affinity-labeling of the nociceptin ORL1 receptor using a thiol activated Cys(Npys)-containing peptide ligand. AB - We previously showed that an antagonist-based peptide ligand, H-Cys(Npys)-Arg-Tyr Tyr-Arg- Ile-Lys-NH2 , captures the free thiol groups in the ligand-binding site of the nociceptin receptor ORL1. However, the exact receptor sites of this thiol disulfide exchange reaction have not been uncovered, although such identification would help to clarify the ligand recognition site. Since the Cys->Ala substitution prevents the reaction, we performed the so-called Ala scanning for all the Cys residues in the transmembrane (TM) domains of the ORL1 receptor. Seven different mutant receptors were soundly expressed in the COS-7 cells and examined for their specific affinity labeling by a competitive binding assay using nociceptin and [(3) H]nociceptin. The results of in vitro Ala scanning analyses revealed that the labeled residues were Cys59 in TM1, Cys215 and Cys231 in TM5, and Cys310 in TM7. The present study has provided a novel method of Cys(Npys)-affinity labeling for identification of the ligand-binding sites in the ORL1 receptor. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 460 469, 2016. PMID- 27271344 TI - Activation of the Renin-Angiotensin System Promotes Colitis Development. AB - The renin-angiotensin system (RAS) plays pathogenic roles in renal and cardiovascular disorders, but whether it is involved in colitis is unclear. Here we show that RenTgMK mice that overexpress active renin from the liver developed more severe colitis than wild-type controls. More than 50% RenTgMK mice died whereas all wild-type mice recovered. RenTgMK mice exhibited more robust mucosal TH17 and TH1/TH17 responses and more profound colonic epithelial cell apoptosis compared to wild-type controls. Treatment with aliskiren (a renin inhibitor), but not hydralazine (a smooth muscle relaxant), ameliorated colitis in RenTgMK mice, although both drugs normalized blood pressure. Chronic infusion of angiotensin II into wild-type mice mimicked the severe colitic phenotype of RenTgMK mice, and treatment with losartan [an angiotensin type 1 receptor blocker (ARB)] ameliorated colitis in wild-type mice, confirming a colitogenic role for the endogenous RAS. In human biopsies, pro-inflammatory cytokines were suppressed in patients with inflammatory bowel disease who were on ARB therapy compared to patients not receiving ARB therapy. These observations demonstrate that activation of the RAS promotes colitis in a blood pressure independent manner. Angiotensin II appears to drive colonic mucosal inflammation by promoting intestinal epithelial cell apoptosis and mucosal TH17 responses in colitis development. PMID- 27271347 TI - Enhancing magnetoresistance in tetrathiafulvalene carboxylate modified iron oxide nanoparticle assemblies. AB - We report a facile approach to stabilize Fe3O4 nanoparticles (NPs) by using tetrathiafulvalene carboxylate (TTF-COO(-)) and to control electron transport with an enhanced magnetoresistance (MR) effect in TTF-COO-Fe3O4 NP assemblies. This TTF-COO-coating is advantageous over other conventional organic coatings, making it possible to develop stable Fe3O4 NP arrays for sensitive spintronics applications. PMID- 27271349 TI - The use of the terrestrial snails of the genera Megalobulimus and Thaumastus as representatives of the atmospheric carbon reservoir. AB - In Brazilian archaeological shellmounds, many species of land snails are found abundantly distributed throughout the occupational layers, forming a contextualized set of samples within the sites and offering a potential alternative to the use of charcoal for radiocarbon dating analyses. In order to confirm the effectiveness of this alternative, one needs to prove that the mollusk shells reflect the atmospheric carbon isotopic concentration in the same way charcoal does. In this study, 18 terrestrial mollusk shells with known collection dates from 1948 to 2004 AD, around the nuclear bombs period, were radiocarbon dated. The obtained dates fit the SH1-2 bomb curve within less than 15 years range, showing that certain species from the Thaumastus and Megalobulimus genera are reliable representatives of the atmospheric carbon isotopic ratio and can, therefore, be used to date archaeological sites in South America. PMID- 27271350 TI - Supramolecular protection from the enzymatic tyrosine phosphorylation in a polypeptide. AB - Here we report two new artificial pseudopeptidic cages that bind the EYE peptide epitope in pure water at physiological pH (as studied by fluorescence and NMR spectroscopies). The supramolecular complexation of the Tyr residues efficiently precludes their subsequent PTK-catalysed phosphorylation. Our results show a supramolecular modulation of the PTK activity by competitive substrate caging. PMID- 27271348 TI - Of the multiple mechanisms leading to type 1 diabetes, T cell receptor revision may play a prominent role (is type 1 diabetes more than a single disease?). AB - A single determinant factor for autoimmunity does not exist; disease development probably involves contributions from genetics, the environment and immune dysfunction. Type 1 diabetes is no exception. Genomewide-associated studies (GWAS) analysis in T1D has proved disappointing in revealing contributors to disease prediction; the only reliable marker has been human leucocyte antigen (HLA). Specific HLAs include DR3/DR4/DQ2/DQ8, for example. Because HLA molecules present antigen to T cells, it is reasonable that certain HLA molecules have a higher affinity to present self-antigen. Recent studies have shown that additional polymorphisms in HLA that are restricted to autoimmune conditions are further contributory. A caveat is that not all individuals with the appropriate 'pro-autoimmune' HLA develop an autoimmune disease. Another crucial component is autoaggressive T cells. Finding a biomarker to discriminate autoaggressive T cells has been elusive. However, a subset of CD4 helper cells that express the CD40 receptor have been described as becoming pathogenic. An interesting function of CD40 on T cells is to induce the recombination-activating gene (RAG)1/RAG2 T cell receptor recombination machinery. This observation is contrary to immunology paradigms that changes in TCR molecules cannot take place outside the thymic microenvironment. Alteration in TCR, called TCR revision, not only occurs, but may help to account for the development of autoaggressive T cells. Another interesting facet is that type 1 diabetes (T1D) may be more than a single disease; that is, multiple cellular components contribute uniquely, but result ultimately in the same clinical outcome, T1D. This review considers the process of T cell maturation and how that could favor auto-aggressive T cell development in T1D. The potential contribution of TCR revision to autoimmunity is also considered. PMID- 27271351 TI - Poor glycemic control is associated with the risk of subclinical hypothyroidism in patients with type 2 diabetes mellitus. AB - BACKGROUND/AIMS: Overt hypothyroidism is frequently found in patients with type 2 diabetes mellitus (T2DM), but it remains unknown the relationship between subclinical hypothyroidism (SCH) and T2DM. We attempt to evaluate the difference in prevalence of SCH between patients with T2DM and general population, and the association between SCH and glycemic control status ofdiabetic patients. METHODS: This was cross-sectional study. Total 8,528 subjects who visited for health check up were recruited. SCH was defined as an elevated level of serum thyroid stimulating hormone (> 4.0 mIU/L) with a normal level of free thyroxine. T2DM group was categorized into three groups by glycosylated hemoglobin (HbA1c): < 7% (reference), >= 7% and < 9%, >= 9%. RESULTS: Finally, 7,966 subjects were included. The prevalence of SCH was not different between healthy controls and subjects with T2DM (8.1% vs. 7.4%, p = 0.533; in men, 5.7% vs. 5.1%, p = 0.573; in women, 10.9% vs. 11.7%, p = 0.712), but it was increased with highest HbA1c group more than well controlled group, especially in women. The risk of SCH was increased by group with poorer glycemic control; the odds ratio for HbA1c >= 9% compared to < 7% was 2.52 (95% confidence interval [CI], 1.09 to 5.86; p = 0.031), and 4.58 (95% CI, 1.41 to 14.87; p = 0.011) in women, but not significant in men. CONCLUSIONS: The prevalence of SCH was similar between T2DM and healthy group. Poor glycemic control in T2DM was obviously associated with the risk of SCH, especially in elderly women. These results suggest SCH as comorbidity may be considered in elderly women with poor glycemic control. PMID- 27271352 TI - Collective electronic excitations in the ultra violet regime in 2-D and 1-D carbon nanostructures achieved by the addition of foreign atoms. AB - Plasmons in the visible/UV energy regime have attracted great attention, especially in nano-materials, with regards to applications in opto-electronics and light harvesting; tailored enhancement of such plasmons is of particular interest for prospects in nano-plasmonics. This work demonstrates that it is possible, by adequate doping, to create excitations in the visible/UV regime in nano-carbon materials, i.e., carbon nanotubes and graphene, with choice of suitable ad-atoms and dopants, which are introduced directly into the lattice by low energy ion implantation or added via deposition by evaporation. Investigations as to whether these excitations are of collective nature, i.e., have plasmonic character, are carried out via DFT calculations and experiment based extraction of the dielectric function. They give evidence of collective excitation behaviour for a number of the introduced impurity species, including K, Ag, B, N, and Pd. It is furthermore demonstrated that such excitations can be concentrated at nano-features, e.g., along nano-holes in graphene through metal atoms adhering to the edges of these holes. PMID- 27271354 TI - Palliative care needs at different phases in the illness trajectory: a survey study in patients with cancer. AB - Despite the growing consensus on the benefits of initiating palliative care early in the disease trajectory, it remains unclear at what point palliative care needs emerge. This study investigates quality of life and unmet palliative care needs at three phases in the cancer trajectory, curative, life-prolonging and most advanced (prognosis <6 months/no further disease-modifying treatment). We collected self-reported data from 620 patients with cancer in the University Hospital of Ghent, Belgium. They completed a questionnaire on quality of life (using the EORTC QLQ-C30) and unmet care needs within the domains of palliative care. We used European reference values of the EORTC QLQ-C30 to compare the mean scores with a norm group. The groups further on in the cancer trajectory reported statistically and clinically poorer functioning compared with earlier phases, also when controlled for the effects of sex, age or type of cancer. Higher symptom burdens for fatigue, pain, dyspnoea and appetite loss were found in groups further into the trajectory, p < .001. Patients in the curative phase experienced physical symptoms and had clinically worse functioning than a European reference group. This paper demonstrates the ongoing need for oncologists to address the broader palliative care needs of patients from diagnosis onwards. PMID- 27271353 TI - Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders. AB - PSD-95 associated PSD proteins play a critical role in regulating the density and activity of glutamate receptors. Numerous previous studies have shown an association between the genes that encode these proteins and schizophrenia (SZ) and autism spectrum disorders (ASD), which share a substantial portion of genetic risks. We sequenced the protein-encoding regions of DLG1, DLG2, DLG4, DLGAP1, DLGAP2, and SynGAP in 562 cases (370 SZ and 192 ASD patients) on the Ion PGM platform. We detected 26 rare (minor allele frequency <1%), non-synonymous mutations, and conducted silico functional analysis and pedigree analysis when possible. Three variants, G344R in DLG1, G241S in DLG4, and R604C in DLGAP2, were selected for association analysis in an independent sample set of 1315 SZ patients, 382 ASD patients, and 1793 healthy controls. Neither DLG4-G241S nor DLGAP2-R604C was detected in any samples in case or control sets, whereas one additional SZ patient was found that carried DLG1-G344R. Our results suggest that rare missense mutations in the candidate PSD genes may increase susceptibility to SZ and/or ASD. These findings may strengthen the theory that rare, non-synonymous variants confer substantial genetic risks for these disorders. PMID- 27271355 TI - Mycobacterium bovis Bacillus Calmette-Guerin vaccination-associated osteomyelitis, arthritis, and tenosynovitis on the thumb of a 2-year-old boy. PMID- 27271358 TI - May-Thurner syndrome: MDCT findings and clinical correlates. AB - May-Thurner syndrome (MTS) is a venous compression syndrome in which the left common iliac vein is compressed between the lower lumbar spine and the right common iliac artery. While asymptomatic compression is very common, the process can lead to morbidity in selected individuals, most commonly deep venous thrombosis (DVT) and the sequelae thereof. Radiologists must recognize the diagnosis because of the unique management, which differs from DVT without iliac vein compression. The current pictorial essay will review the pathophysiology, imaging, and treatment of MTS. PMID- 27271357 TI - Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China. AB - BACKGROUND: Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. METHODS: Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. RESULTS: In the base-case analysis, the lowest lifetime cost and the best cost effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 * gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. CONCLUSIONS: For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained. PMID- 27271359 TI - Synthesis and reactivity of Li and TaMe3 complexes supported by N,N'-bis(2,6 diisopropylphenyl)-o-phenylenediamido ligands. AB - The dilithium complex of N,N'-bis(2,6-diisopropylphenyl)-o-phenylenediamide, [Li2L(thf)3], reacts with TaMe3Cl2 in THF/Et2O to yield [Li(Et2O)(thf)LTaMe3Cl] in which the phenylene backbone of (2-) is bound eta(4) to the Ta centre. This dinuclear species reacts with MeLi to yield the tetramethyltantalum complex [Li(Et2O)(thf)LTaMe4]. Double deprotonation of N,N'-bis(2,6 diisopropylphenyl)(4,5-dimethyl)-o-phenylenediamine (H2L') in Et2O yielded the dilithium complex [Li2L'(OEt2)2]. The two additional methyl groups on L'(2-) change the observed reactivity towards TaMe3Cl2: rather than bridging between Ta and Li, ligand oxidation occurs to afford mononuclear [LiL'(OEt2)]. This monolithium radical species, which was characterized by EPR spectroscopy, can also be synthesized using the more conventional oxidant AgBF4. Double deprotonation of H2L with KCH2Ph in toluene followed by reaction with TaMe3Cl2 furnished [TaLMe3]. Preliminary reactivity studies show [TaLMe3] reacts with unsaturated substrates N,N'-dicyclohexylcarbodiimide and mesityl azide to undergo migratory insertion into one of the Ta-C bonds: the corresponding amidinate and triazenido ligands are generated. When subjected to UV irradiation, [TaLMe3] undergoes reduction accompanied by loss of a methyl group to yield the dimeric species [TaLMe2]2. PMID- 27271356 TI - Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers around the globe and third most fatal malignancy. Chronic liver disorders such as chronic hepatitis and liver cirrhosis often lead to the development of HCC. Accumulation of genetic and epigenetic alterations are involved in the development of HCC. Genetic research sparked by recent developments in next generation sequencing has identified the frequency of genetic alterations that occur in HCC and has led to the identification of genetic hotspots. Emerging evidence suggests that epigenetic aberrations are strongly associated with the initiation and development of HCC. Various important genes encoding tumor suppressors including P16, RASSF1A, DLC-1, RUNX3 and SOCS-1 are targets of epigenetic dysregulation during the development of HCC. The present review discusses the importance of epigenetic regulations including DNA methylation, histone modification and microRNA mediated regulation of gene expression during tumorigenesis and their use as disease biomarkers. Furthermore, these epigenetic alterations have been discussed in relationship with promising therapeutic perspectives for HCC and related cancers. PMID- 27271360 TI - Perception of barriers to postoperative pain management in elderly patients in Polish hospitals - a multicentre study. AB - AIM: The purpose of the paper was to compare the prevalence of barriers to optimum postoperative pain management in elderly patients, observed by nurses in a clinical, provincial and municipal hospital in Poland. BACKGROUND: It is currently estimated that the lack of adequate pain management affects 80% of the global population and the phenomenon poses a serious problem in more than 150 countries. METHODS: A questionnaire-based study of 1602 nurses working at clinical, provincial and municipal hospitals. RESULTS: In the clinical hospitals barriers more often related to a poorly organised systems of care and obstacles in discussing pain management within the team. In provincial and municipal hospitals lack of uninform pain measurement was more evident. CONCLUSIONS: Despite the availability of effective pain treatments in hospitals difficulties continue with communication, poorly organised care and limited access to clinical guidelines. IMPLICATIONS FOR NURSING MANAGEMENT: Although there are possibilities of pain relief after surgery, they are still used insufficiently. Postoperative pain management in Poland needs considerable improvement. This study can contribute to the improvement of pain management quality by supporting and developing practical guidelines or management algorithms for nurses, facilitating the effective implementation of new pain management practices. PMID- 27271361 TI - Polymorphism in promoter region of growth hormone receptor is associated with potential production capacity of insulin-like growth factor-1 in pre-pubertal Holstein heifers. AB - Insulin-like growth factor-1 (IGF-1) is one of the important factors for growth, milk production and reproductive functions and mainly released from the liver in response to growth hormone (GH) via GH receptor (GHR) in cattle. Recently, some single nucleotide polymorphisms (SNPs) were identified in the bovine GHR gene. Some GHR-SNPs were shown to be related to plasma IGF-1 concentration in cattle. Hence, the capacity to IGF-1 production in the liver might be affected by GHR-SNP and associated with performance in the future. This study examined whether GHR SNP is associated with IGF-1 production in the liver of pre-pubertal heifers. In 71 Holstein calves, blood samples for genomic DNA extraction were obtained immediately after birth. To genotype the GHR-SNPs in the promoter region, polymerase chain reaction (PCR) products were digested with restriction enzyme NsiI (cutting sites: AA, AG and GG). All heifers at 4 months of age were intramuscularly injected with 0.4 mg oestradiol benzoate. Blood samples were obtained from the jugular vein just before (0 h) and 24 h after injection. The number of AA, AG and GG at the NsiI site was 0, 17 and 54 respectively. In AG and GG, plasma GH concentrations were higher pre-injection than 24 h post-injection (p < 0.01). Moreover, plasma GH concentrations in AG post-injection were higher than in GG (p < 0.05). In contrast, the GG genotype exhibited higher plasma IGF-1 concentrations in pre-injection than post-injection (p < 0.01), although oestradiol did not change IGF-1 concentration in the AG genotype. We conclude that the GG polymorphism in the promoter region of GHR is associated with a higher potential capacity of IGF-1 production in the liver of cattle. PMID- 27271363 TI - Differential activation of afferent neuronal and inflammatory pathways during small bowel obstruction (SBO). AB - BACKGROUND: Small bowel obstruction (SBO) is a potentially life-threatening condition which may be caused by a variety of pathologies such as postoperative adhesions or malignant diseases. Little is known on alterations in gut physiology during SBO, although its comprehension is essential to improve treatment which may help to prevent subsequent organ failure prior to surgical resolution. We aimed to investigate afferent nerve sensitivity and intestinal inflammatory response during SBO to identify possible targets of treatment. METHODS: C57Bl6 mice were anesthetized, and a midline laparotomy was performed. A small bowel loop was ligated 5 cm proximal to ileo-cecal valve to induce SBO. Control animals received a sham midline laparotomy. SBO animals and controls were sacrificed after 3, 9, or 24 h (each n = 6). A dilated segment of small intestine located 1.5 cm oral to the ligature was prepared for multi-unit mesenteric afferent nerve recordings in vitro. Histological assessment of leukocyte infiltration was performed by myeloperoxidase (MPO). Pro-inflammatory cytokine expression was quantified by RT-PCR. Data are mean +/- SEM. KEY RESULTS: Afferent firing to serosal 5-HT (500 MUM) peaked at 3.9 +/- 0.2 impulse/s 24 h after induction of SBO compared to 2.4 +/- 0.1 impulse/s in sham controls (p < 0.05). Serosal bradykinin (0.5 MUM) led to an increase in peak afferent firing of 5.3 +/- 0.5 impulse/s in 24 h SBO animals compared to 3.5 +/- 0.2 impulse/s in sham controls (p < 0.05). No differences in 5-HT and BK sensitivity were observed in 3 and 9 h SBO animals compared to controls. Continuous mechanical ramp distension of the intestinal loop was followed by a pressure-dependent rise in afferent nerve discharge that was reduced in 3 h SBO animals compared to sham controls (p < 0.05). MPO stains showed a rise in leukocyte infiltration of the intestine in SBO animals at 9 and 24 h (p < 0.05). Il-6 but not TNF-a gene expression was increased at 9 and 24 h in SBO animals compared to sham controls (p < 0.05). CONCLUSIONS & INFERENCES: Afferent nerve sensitivity is increased 24 h after induction of SBO. SBO led to a delayed onset intestinal inflammatory response. Inflammatory mediators released during this inflammatory response may be responsible for a later increase in afferent sensitivity. Agents with anti inflammatory action may, therefore, have a beneficial effect during SBO and may subsequently help to prevent possible organ dysfunction. PMID- 27271362 TI - The evolution of mating type switching. AB - Predictions about the evolution of sex determination mechanisms have mainly focused on animals and plants, whereas unicellular eukaryotes such as fungi and ciliates have received little attention. Many taxa within the latter groups can stochastically switch their mating type identity during vegetative growth. Here, we investigate the hypothesis that mating type switching overcomes distortions in the distribution of mating types due to drift during asexual growth. Using a computational model, we show that smaller population size, longer vegetative periods and more mating types lead to greater distortions in the distribution of mating types. However, the impact of these parameters on optimal switching rates is not straightforward. We find that longer vegetative periods cause reductions and considerable fluctuations in the switching rate over time. Smaller population size increases the strength of selection for switching but has little impact on the switching rate itself. The number of mating types decreases switching rates when gametes can freely sample each other, but increases switching rates when there is selection for speedy mating. We discuss our results in light of empirical work and propose new experiments that could further our understanding of sexuality in isogamous eukaryotes. PMID- 27271364 TI - Climacostol reduces tumour progression in a mouse model of melanoma via the p53 dependent intrinsic apoptotic programme. AB - Climacostol, a compound produced by the ciliated protozoan Climacostomum virens, displayed cytotoxic properties in vitro. This study demonstrates that it has anti tumour potential. Climacostol caused a reduction of viability/proliferation of B16-F10 mouse melanoma cells, a rapidly occurring DNA damage, and induced the intrinsic apoptotic pathway characterised by the dissipation of the mitochondrial membrane potential, the translocation of Bax to the mitochondria, the release of Cytochrome c from the mitochondria, and the activation of Caspase 9-dependent cleavage of Caspase 3. The apoptotic mechanism of climacostol was found to rely on the up-regulation of p53 and its targets Noxa and Puma. In vivo analysis of B16-F10 allografts revealed a persistent inhibition of tumour growth rate when melanomas were treated with intra-tumoural injections of climacostol. In addition, it significantly improved the survival of transplanted mice, decreased tumour weight, induced a remarkable reduction of viable cells inside the tumour, activated apoptosis and up-regulated the p53 signalling network. Importantly, climacostol toxicity was more selective against tumour than non-tumour cells. The anti-tumour properties of climacostol and the molecular events associated with its action indicate that it is a powerful agent that may be considered for the design of pro-apoptotic drugs for melanoma therapy. PMID- 27271365 TI - Cognitive Representation of Treatment-Related Symptoms in Older Adults With Cancer. AB - BACKGROUND: Adults, 65 years or older, are the most common age group diagnosed with cancer. However, little is known about their beliefs (representations) regarding treatment-related symptoms or how they make decisions to manage those symptoms at home. OBJECTIVE: The aim of this study is to explore symptom representation of treatment-related symptoms in older adults with cancer. METHODS: A total of 100 older adults in treatment for cancer completed a standardized measure of symptom representation. Demographic and other patient variables were also collected. Analysis of variance, t tests, and Pearson correlations were used for analysis. RESULTS: Fatigue was both the most common and most noted symptom; however, several most noted symptoms were not common. Overall, older adults believed symptoms were caused by either their cancer or treatment and were unsure if symptoms would last a long time. They were able to recognize symptom consequences but were unsure about their ability to control symptoms. Adults who reported more comorbid illnesses and a higher number of symptoms believed that treatment-related symptoms had higher consequences. CONCLUSIONS: Findings suggest that older adults experience symptom-related consequences but question the impact that their actions will have on symptom severity. This may contribute to older adult's lack of active symptom self management. IMPLICATIONS FOR PRACTICE: Patient education strategies need to address these representations and new interventions may need to be developed to reinforce symptom consequences and empower older adults to self-manage symptoms. PMID- 27271366 TI - A Prevalence Study of Psychosocial Distress in Adolescents and Young Adults With Cancer. AB - BACKGROUND: Psychosocial distress is common among cancer patients. Significant associations between coping and social support with distress and quality of life in adult cancer patients have been identified before, but little is known about the interrelationships between distress, medical coping, and social support in adolescents and young adults (AYAs). OBJECTIVE: The aims of this study are to investigate the prevalence of psychological distress in Chinese AYAs with cancer and examine the associations among distress, anxiety and depression, medical coping, and social support in the same population. METHODS: A total of 610 AYA patients were recruited for this study; 551 patients completed the Chinese version of the National Comprehensive Cancer Network Distress Thermometer (DT), the Hospital Anxiety and Depression Scale, the Medical Coping Modes Questionnaire, and the Social Support Rating Scale. RESULTS: The prevalence of psychological distress was 89.1% in Chinese AYAs with cancer. The DT scores were the highest in the 21- to 25-year-old patients; the DT scores were positively correlated with anxiety and depression (P < .01) but negatively correlated with medical coping and social support (P < .01). CONCLUSION: The prevalence of psychological distress in AYA cancer patients was higher than that in the general cancer population. Medical coping and social support can lower the prevalence of psychological distress in AYA cancer patients. IMPLICATIONS FOR PRACTICE: Findings suggest the need for evidence-based intervention strategies to enhance medical coping and social support in AYA cancer patients. Nurses are crucial to implementing psychological interventions in AYA cancer patients. PMID- 27271367 TI - "I Had a Little Bit of a Bloke Meltdown...But the Next Day, I Was Up": Understanding Cancer Experiences Among Aboriginal Men. AB - BACKGROUND: Although cancer in indigenous populations is receiving increased research attention, there is a gap in understanding the particular experiences of Aboriginal men. OBJECTIVE: The aim of this study is to integrate a range of primary and secondary accounts of the experiences of Aboriginal men in engaging with a cancer diagnosis and treatment in Australia. METHODS: Secondary analysis of qualitative interviews (n = 54) conducted between 2008 and 2011 revealed recurrent themes regarding the cancer experiences of Aboriginal men in a subset of participant interviews (n = 23). The analysis reports themes that spanned the accounts of Aboriginal men with cancer (n = 6) and those of their carers (n = 12) and clinicians (n = 5). RESULTS: Recurrent beliefs about the cancer experiences of Aboriginal men included that they "avoid seeking help" for health matters, including cancer symptoms, and to "get on with it," "not talk about it," and "manage without fuss" after a cancer diagnosis. Although some men described having to "accept vulnerability," emphasis was placed on appreciating men's desire to "protect cultural roles" and "connect with family and culture" throughout care and treatment, including through humor. CONCLUSIONS: Men's accounts of the experiences of cancer diagnosis and care reveal more than simply individual challenge, extending to encompass the very real social and economic implications of illness and vulnerability for Aboriginal men today. IMPLICATIONS FOR PRACTICE: Aboriginal men could be better engaged with cancer diagnosis and treatment if greater attention was paid to recognizing preferred approaches, including pragmatism and humor, and supporting connections to family and culture throughout the cancer journey. PMID- 27271368 TI - Application of Osmotic Pumps for Sustained Release of 1-Aminobenzotriazole and Inhibition of Cytochrome P450 Enzymes in Mice: Model Comparison with the Hepatic P450 Reductase Null Mouse. AB - The effectiveness of controlled release 1-aminobenzotriazole (ABT) administration to inhibit cytochrome P450 (P450) enzymes has been evaluated in mice. To maximize the duration of P450 inhibition in vivo, ABT was administered via an osmotic pump. The degree of P450 inhibition was compared with that achieved with a single bolus dose of ABT. Two-hour prior subcutaneous treatment of mice with ABT (50 mg/kg) inhibited antipyrine clearance by 88%. A less pronounced inhibitory effect (29% reduction in clearance) was observed when ABT was administered 24-hours before antipyrine administration, indicating partial restoration of P450 activity during this longer pretreatment time. The duration of ABT in mice was very short (mean residence time = 1.7 hours) after subcutaneous bolus administration. When the inhibitor was delivered by an osmotic pump, maximum blood concentrations of the inhibitor were observed 24 hours after device implantation and were maintained at steady state for 6 days. Inhibition of P450 activity, as measured by antipyrine clearance, was confirmed at 24 hours and 120 hours after pump implantation, highlighting the utility of this method as a longer-term model for P450 inhibition in mice. The magnitude of P450 inhibition in ABT-treated mice was compared with that in hepatic P450 reductase null mice and both models were comparable. In vivo ABT administration by an osmotic pump offers an effective approach for longer-term P450 inhibition in mice and avoids the necessity for multiple dosing of the inhibitor. PMID- 27271370 TI - Impact of Experimental Conditions on the Evaluation of Interactions between Multidrug and Toxin Extrusion Proteins and Candidate Drugs. AB - Multidrug and toxin extrusion transporters (MATEs) have a determining influence on the pharmacokinetic profiles of many drugs and are involved in several clinical drug-drug interactions (DDIs). Cellular uptake assays with recombinant cells expressing human MATE1 or MATE2-K are widely used to investigate MATE mediated transport for DDI assessment; however, the experimental conditions and used test substrates vary among laboratories. We therefore initially examined the impact of three assay conditions that have been applied for MATE substrate and inhibitor profiling in the literature. One of the tested conditions resulted in significantly higher uptake rates of the three test substrates, [(14)C]metformin, [(3)H]thiamine, and [(3)H]1-methyl-4-phenylpyridinium (MPP(+)), but IC50 values of four tested MATE inhibitors varied only slightly among the three conditions (<2.5-fold difference). Subsequently, we investigated the uptake characteristics of the five MATE substrates: [(14)C]metformin, [(3)H]thiamine, [(3)H]MPP(+), [(3)H]estrone-3-sulfate (E3S), and rhodamine 123, as well as the impact of the used test substrate on the inhibition profiles of 10 MATE inhibitors at one selected assay condition. [(3)H]E3S showed atypical uptake characteristics compared with those observed with the other four substrates. IC50 values of the tested inhibitors were in a similar range (<4-fold difference) when [(14)C]metformin, [(3)H]thiamine, [(3)H]MPP(+), or [(3)H]E3S were used as substrates but were considerably higher with rhodamine 123 (9.8-fold and 4.1-fold differences compared with [(14)C]metformin with MATE1 and MATE2-K, respectively). This study demonstrated for the first time that the impact of assay conditions on IC50 determination is negligible, that kinetic characteristics differ among used test substrates, and that substrate-dependent inhibition exists for MATE1 and MATE2-K, giving valuable insight into the assessment of clinically relevant MATE mediated DDIs in vitro. PMID- 27271369 TI - Use of Human Plasma Samples to Identify Circulating Drug Metabolites that Inhibit Cytochrome P450 Enzymes. AB - Drug interactions elicited through inhibition of cytochrome P450 (P450) enzymes are important in pharmacotherapy. Recently, greater attention has been focused on not only parent drugs inhibiting P450 enzymes but also on possible inhibition of these enzymes by circulating metabolites. In this report, an ex vivo method whereby the potential for circulating metabolites to be inhibitors of P450 enzymes is described. To test this method, seven drugs and their known plasma metabolites were added to control human plasma at concentrations previously reported to occur in humans after administration of the parent drug. A volume of plasma for each drug based on the known inhibitory potency and time-averaged concentration of the parent drug was extracted and fractionated by high-pressure liquid chromatography-mass spectrometry, and the fractions were tested for inhibition of six human P450 enzyme activities (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). Observation of inhibition in fractions that correspond to the retention times of metabolites indicates that the metabolite has the potential to contribute to P450 inhibition in vivo. Using this approach, norfluoxetine, hydroxyitraconazole, desmethyldiltiazem, desacetyldiltiazem, desethylamiodarone, hydroxybupropion, erythro-dihydrobupropion, and threo dihydrobupropion were identified as circulating metabolites that inhibit P450 activities at a similar or greater extent as the parent drug. A decision tree is presented outlining how this method can be used to determine when a deeper investigation of the P450 inhibition properties of a drug metabolite is warranted. PMID- 27271371 TI - Correlation of Cytochrome P450 Oxidoreductase Expression with the Expression of 10 Isoforms of Cytochrome P450 in Human Liver. AB - Human cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (P450s) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 12.8-fold, from 12.59 to 160.97 pmol/mg, with a median value of 67.99 pmol/mg; POR mRNA expression varied by 26.4-fold. POR activity was less variable with a median value of 56.05 nmol/min per milligram. Cigarette smoking and alcohol consumption clearly influenced POR activity. Liver samples with a 2286822 TT genotype had significantly higher POR mRNA expression than samples with CT genotype. Homozygous carriers of POR2286822C>T, 2286823G>A, and 3823884A>C had significantly lower POR protein levels compared with the corresponding heterozygous carriers. Liver samples from individuals homozygous at 286823G>A, 1135612A>G, and 10954732G>A generally had lower POR activity levels than those from heterozygous or wild-type samples, whereas the common variant POR*28 significantly increased POR activity. There was a strong association between POR and the expression of P450 isoforms at the mRNA and protein level, whereas the relationship at the activity level, as well as the effect of POR protein content on P450 activity, was less pronounced. POR transcription was strongly correlated with both hepatocyte nuclear factor 4 alpha and pregnane X receptor mRNA levels. In conclusion, we have elucidated some potentially important correlations between POR single-nucleotide polymorphisms and POR expression in the Chinese population and have developed a database that correlates POR expression with the expression and activity of 10 P450s important in drug metabolism. PMID- 27271372 TI - Effects of Chronic Renal Failure on Brain Cytochrome P450 in Rats. AB - Chronic renal failure (CRF) impedes renal excretion of drugs and their metabolism by reducing the expression of liver cytochrome P450 (P450). Uremic serum contains factors, such as parathyroid hormone (PTH), that decrease liver P450s. The P450s are also involved in the metabolism of xenobiotics in the brain. This study investigates: 1) the effects of CRF on rat brain P450, 2) the role of PTH in the downregulation of brain P450s in CRF rats, and 3) the effects of PTH on P450s in astrocytes. Protein and mRNA expression of P450s were assessed in the brain of CRF and control (CTL) rats, as well as from CTL or CRF rats that underwent parathyroidectomy (PTX) 1 week before nephrectomy. CYP3A activity was measured using 3-[(3, 4-difluorobenzyl) oxy]-5, 5-dimethyl-4-[4-methylsulfonyl) phenyl] furan-2(5H)-1 metabolism in brain microsomal preparation. CYP3A protein expression was assessed in primary cultured astrocytes incubated with serum obtained from CRF or CTL rats or with PTH. Significant downregulations (>=40%) of CYP1A, CYP2C11, and CYP3A proteins were observed in microsomes from CRF rat brains. CYP3A activity reduction was also observed. CYP3A expression and activity were unaffected in PTX-pretreated CRF rats. Serum of PTX-treated CRF rats had no impact on CYP3A levels in astrocytes compared with that of untreated CRF rats. Finally, PTH addition to normal calf serum induced a reduction in CYP3A protein similar to CRF serum, suggesting that CRF-induced hyperparathyroidism is associated with a significant decrease in P450 drug-metabolizing enzymes in the brain, which may have implications in drug response. PMID- 27271373 TI - Respiratory muscle strength training and neuromuscular electrical stimulation in subacute dysphagic stroke patients: a randomized controlled trial. AB - OBJECTIVE: To evaluate the effectiveness of inspiratory/expiratory muscle training (IEMT) and neuromuscular electrical stimulation (NMES) to improve dysphagia in stroke. DESIGN: Prospective, single-blind, randomized-controlled trial. SETTING: Tertiary public hospital. SUBJECTS: Sixty-two patients with dysphagia were randomly assigned to standard swallow therapy (SST) (Group I, controls, n=21), SST+ IEMT (Group II, n=21) or SST+ sham IEMT+ NMES (Group III, n=20). INTERVENTIONS: All patients followed a 3-week standard multidisciplinary rehabilitation program of SST and speech therapy. The SST+IEMT group's muscle training consisted of 5 sets/10 repetitions, twice-daily, 5 days/week. Group III's sham IEMT required no effort; NMES consisted of 40-minute sessions, 5 days/week, at 80Hz. MAIN OUTCOMES: Dysphagia severity, assessed by Penetration Aspiration Scale, and respiratory muscle strength (maximal inspiratory and expiratory pressures) at the end of intervention and 3-month follow-up. RESULTS: Maximal respiratory pressures were most improved in Group II: treatment effect was 12.9 (95% confidence interval 4.5-21.2) and 19.3 (95% confidence interval 8.5 30.3) for maximal inspiratory and expiratory pressures, respectively. Swallowing security signs were improved in Groups II and III at the end of intervention. No differences in Penetration-Aspiration Scale or respiratory complications were detected between the 3 groups at 3-month follow-up. CONCLUSION: Adding IEMT to SST was an effective, feasible, and safe approach that improved respiratory muscle strength. Both IEMT and NMES were associated with improvement in pharyngeal swallowing security signs at the end of the intervention, but the effect did not persist at 3-month follow-up and no differences in respiratory complications were detected between treatment groups and controls. PMID- 27271374 TI - Randomized controlled trial of web-based multimodal therapy for children with acquired brain injury to improve gross motor capacity and performance. AB - OBJECTIVE: To compare efficacy of a web-based multimodal training programme, 'Move it to improve it' (MitiiTM), to usual care on gross motor capacity and performance for children with an acquired brain injury. DESIGN: Randomized waitlist controlled trial. SETTING: Home environment. PARTICIPANTS: A total of 60 independently ambulant children (30 in each group), minimum 12 months post acquired brain injury were recruited and randomly allocated to receive either 20 weeks of MitiiTM training (30 minutes/day, six days/week, total 60 hours) immediately, or waitlisted (usual care control group) for 20 weeks. A total of 58 children completed baseline assessments (32 males; age 11 years 11 months +/- 2 years 6 months; Gross Motor Function Classification System equivalent I = 29, II = 29). INTERVENTION: The MitiiTM program comprised of gross motor, upper limb and visual perception/cognitive activities. MAIN MEASURES: The primary outcome was 30 second, repetition maximum functional strength tests for the lower limb (sit-to stand, step-ups, half-kneel to stand). Secondary outcomes were the 6-minute walk test, High-level Mobility Assessment Tool, Timed Up and Go Test and habitual physical activity as captured by four-day accelerometry. RESULTS: Groups were equivalent at baseline on demographic and clinical measures. The MitiiTM group demonstrated significantly greater improvements on combined score of functional strength tests (mean difference 10.19 repetitions; 95% confidence interval, 3.26 17.11; p = 0.006) compared with the control group. There were no other between group differences on secondary outcomes. CONCLUSION: Although the MitiiTM programme demonstrated statistically significant improvements in the functional strength tests of the lower limb, results did not exceed the minimum detectable change and cannot be considered clinically relevant for children with an acquired brain injury. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registration Number, ANZCTR12613000403730. PMID- 27271375 TI - Determination of the inhibitor dissociation constant of an individual unmodified enzyme molecule in free solution. AB - Single enzyme molecule assays on E. coli beta-galactosidase were performed using a capillary electrophoresis-based method. Three types of assays were performed. The catalytic rate of 20 individual molecules was assayed in duplicate in the presence of 50 MUM substrate. The ratio of rates for the second incubation relative to the first was 0.96 +/- 0.03, showing the reproducibility of the method. In the second assay, the rates were determined in the absence and presence of 210 MUM L-ribose, a competitive inhibitor. The ratio of the rate in the presence of inhibitor to that in its absence for 19 individual molecules was 0.44 +/- 0.23. This large relative standard deviation suggests that each individual enzyme molecule was affected to a different extent by the presence of the inhibitor, which is consistent with KI being heterogeneous. To estimate KI for individual molecules, a third assay was performed. Each molecule was incubated in the presence of 30 and 50 MUM substrate and then in the presence of 50 MUM substrate plus 210 MUM inhibitor. Comparison of the rates in the two substrate concentrations allowed for the determination of the individual Km of each molecule. From this value and the difference in rates in the presence and absence of inhibitor, the individual molecule KI values were determined. This value was found to differ between individual molecules and was found to increase with an increase in Km . Modeling showed that a heterogeneity in KI results in an alteration in the Michaelis-Menten curve for a population of enzymes in the presence of a competitive inhibitor. PMID- 27271378 TI - [Cognitive deficits in young snorers]. PMID- 27271380 TI - [What is causing the pain and hematomas?]. PMID- 27271376 TI - Pd@Ag Nanosheets in Combination with Amphotericin B Exert a Potent Anti Cryptococcal Fungicidal Effect. AB - Silver nanoparticles have received considerable interest as new "nanoantibiotics" with the potential to kill drug-resistant microorganisms. Recently, a class of new core-shell nanostructures, Pd@Ag nanosheets (Pd@Ag NSs), were created using deposition techniques and demonstrated excellent inhibitory effects on various bacteria in vitro. In this study, we evaluated the antifungal activity of Pd@Ag NSs against common invasive fungal pathogens. Among these organisms, Cryptococcus neoformans complex species was most susceptible to Pd@Ag NSs, which exhibited potent antifungal activity against various molecular types or sources of cryptococcal strains including fluconazole-resistant isolates. The anticryptococcal activity of Pd@Ag NSs was significantly greater than fluconazole and similar to that of amphotericin B (AmB). At relatively high concentrations, Pd@Ag NSs exhibited fungicidal activity against Cryptococcus spp., which can likely be attributed to the disruption of cell integrity, intracellular protein synthesis, and energy metabolism. Intriguingly, Pd@Ag NSs also exhibited strong synergistic anti-cryptococcal fungicidal effects at low concentrations in combination with AmB but exhibited much better safety in erythrocytes than AmB, even at the minimal fungicidal concentration. Therefore, Pd@Ag NSs may be a promising adjunctive agent for treating cryptococcosis, and further investigation for clinical applications is required. PMID- 27271381 TI - [Psoriasis nails need motivation and patience]. PMID- 27271385 TI - [Medicine in soccer boots]. PMID- 27271386 TI - [Targeted strengthening of hamstring weak areas]. PMID- 27271387 TI - [What do the guidelines say?]. PMID- 27271388 TI - [Dual bronchodilators becomes the first choice combination]. PMID- 27271389 TI - [Lung disease patient on the aircraft: what to consider?]. PMID- 27271390 TI - [Vitamin D deficiency also frequent among the young]. PMID- 27271391 TI - [Brittle bones caused by antidepressants?]. PMID- 27271392 TI - [Regarding elderly men and new procedures]. PMID- 27271393 TI - [First check adherence]. PMID- 27271394 TI - [Should one rather smoke or become fat?]. PMID- 27271395 TI - [New remedies guideline decreases risk of regress starting 1 January 2017]. PMID- 27271397 TI - [Appointment with a somewhat different urologist]. PMID- 27271398 TI - [At least the eggs are intact]. PMID- 27271399 TI - [Letting them wander through their individual reality]. PMID- 27271400 TI - [Usually no sick leave pay during preventative cures]. PMID- 27271401 TI - [Can general practitioners bill local anesthesia?]. PMID- 27271402 TI - [In Number 15 private insurance is responsible]. PMID- 27271403 TI - [Is your practice open to everyone?]. PMID- 27271404 TI - [We promote career chances - also with baby!]. PMID- 27271405 TI - [Not Available]. PMID- 27271407 TI - [Not Available]. PMID- 27271406 TI - [An amalgam tattoo under the tongue]. PMID- 27271408 TI - [A silvery sign in the toilet]. PMID- 27271409 TI - [Not Available]. PMID- 27271410 TI - [Not Available]. PMID- 27271411 TI - [The rewarding alcohol effects are not diminished even in high intake]. PMID- 27271412 TI - [Not Available]. PMID- 27271413 TI - [Knowing avoidable mistakes--well-prepared for postmortem examinations]. PMID- 27271414 TI - [External postmortem examination--choosing between natural and unnatural causes of death]. PMID- 27271415 TI - [Bad mistakes in external examination: avoiding legal consequences]. PMID- 27271416 TI - [Medication review--seven steps to improve pharmacotherapy in elderly adults]. PMID- 27271417 TI - [Good Prognosis! Breast Cancer Update 2016]. PMID- 27271418 TI - [Emergency checklist: Acute lymphangitis]. PMID- 27271419 TI - [Hypoglycemia--simply annoying or dangerous?]. PMID- 27271421 TI - [The first antidote is available]. PMID- 27271422 TI - [Ways to healthy sleep]. PMID- 27271423 TI - [Importance of inhaled corticosteroids under discussion]. PMID- 27271425 TI - [Alginate improves symptom control]. PMID- 27271426 TI - [Early combination therapy pays off]. PMID- 27271427 TI - [New therapies turn oral steroids into reserve agents]. PMID- 27271428 TI - [Early building up of vaccination protection]. PMID- 27271429 TI - [Continuing therapy also in summer]. PMID- 27271430 TI - [Empagliflozin also protects high risk patients]. PMID- 27271431 TI - Homozygous deletion of exons 2 and 3 of NPC2 associated with Niemann-Pick disease type C. PMID- 27271432 TI - Diagnostic Accuracy of Lateral Flow Urine LAM Assay for TB Screening of Adults with Advanced Immunosuppression Attending Routine HIV Care in South Africa. AB - BACKGROUND: We assessed the diagnostic accuracy of Determine TB-LAM (LF-LAM) to screen for tuberculosis among ambulatory adults established in HIV care in South Africa. METHODS: A systematic sample of adults attending for HIV care, regardless of symptomatology, were enrolled in the XPHACTOR study, which tested a novel algorithm for prioritising investigation with Xpert MTB/RIF. In this substudy, restricted to participants with enrolment CD4<200x106/l, urine was stored at enrolment for later testing with LF-LAM. Sputum was sent for immediate Xpert MTB/RIF if any of: current cough, fever >=3 weeks, body mass index (BMI)<18.5kg/m2, CD4<100x106/l (or <200x106/l if pre-ART), weight loss >=10% or strong clinical suspicion were present; otherwise, sputum was stored for Xpert testing at study completion. Participants were reviewed monthly, with reinvestigation if indicated, to 3 months, when sputum and blood were taken for mycobacterial culture. We defined tuberculosis as "confirmed" if Xpert, line probe assay or culture for M. tuberculosis within six months of enrolment were positive, and "clinical" if tuberculosis treatment started without microbiological confirmation. RESULTS: Amongst 424 participants, 61% were female and 57% were taking ART (median duration 22 months); median age, CD4 and BMI were 39 years, 111x106/l, and 23 kg/m2. 56/424 (13%) participants had tuberculosis (40 confirmed, 16 clinical). 24/424 (5.7%) vs. 8/424 (1.9%) were LAM-positive using grade 1 vs. grade 2 cut-off. Using grade 1 cut-off, sensitivity for confirmed TB (all clinical TB excluded) was 12.5% (95% CI 4.2%, 26.8%) and in CD4<100x106/l vs. CD4 >=100x106/l was 16.7% (95% CI 4.7%, 37.4%) vs. 6.3% (95% CI 0.2%, 30.2%). Specificity was >95% irrespective of diagnostic reference standard, CD4 stratum, or whether grade 1 or grade 2 cut-off was used. CONCLUSION: Sensitivity of LF-LAM is too low to recommend as part of intensified case finding in ambulatory patients established in HIV care. PMID- 27271433 TI - Correction: Locked Nucleic Acid Probe-Based Real-Time PCR Assay for the Rapid Detection of Rifampin-Resistant Mycobacterium tuberculosis. AB - [This corrects the article DOI: 10.1371/journal.pone.0143444.]. PMID- 27271434 TI - Increase of forage dryness induces differentiated anatomical response in the sheep rumen compartments. AB - The aim of this study was to investigate how the Surface Enlargement Factor (SEF) and the epithelial keratinization degree of sheep rumen change in response to phytomass production, and to forage fiber and water content during the pasture vegetative cycle. The study used eighteen sheep nourished with dry hay and cereals during the winter season and with fresh hay during the pasture vegetative cycle. We collected samples from rumen indicative regions for two consecutive years characterized by different rainfall and pasture productivity values. We evaluated the densities (D) of rumen papillae to estimate the rumen SEF, and the keratinization percentage of the epithelial lining; these parameters showed differentiated modifications in the four ruminal analyzed compartments in response to pasture seasonal conditions. In addition, we performed Canonical Redundancy Analysis (RDA) on the "keratinization and SEF" matrix constrained by phytomass, water, and crude fiber contents of pasture at different time in the two considered years to highlight how rumen features answer to pasture conditions. Atrium (A) and ventral sac (VS) keratinization showed a strict positive correlation to crude fiber, while SEF of VS was positively related to phytomass and forage water content. The degree of keratinization of the rumen VS epithelium proved to be a useful parameter for evaluating anatomical variations in the short term period related to pasture features; in addition, its monitoring could be carried out through biopsy, thus avoiding the killing of animals. The study also leads to the application of the 3Rs (Replacement; Reduction; and Refinement). Microsc. Res. Tech. 79:738-743, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27271435 TI - Origin of Shear Stability and Compressive Ductility Enhancement of Metallic Glasses by Metal Coating. AB - Metallic glasses (MGs) are notorious for the poor macroscopic ductility and to overcome the weakness various intrinsic and extrinsic strategies have been proposed in past decades. Among them, the metal coating is regarded as a flexible and facile approach, yet the physical origin is poorly understood due to the complex nature of shear banding process. Here, we studied the origin of ductile enhancement in the Cu-coating both experimentally and theoretically. By examining serrated shear events and their stability of MGs, we revealed that the thin coating layer plays a key role in stopping the final catastrophic failure of MGs by slowing down shear band dynamics and thus retarding its attainment to a critical instable state. The mechanical analysis on interplay between the coating layer and shear banding process showed the enhanced shear stability mainly comes from the lateral tension of coating layer induced by the surface shear step and the bonding between the coating layer and MGs rather than the layer thickness is found to play a key role in contributing to the shear stability. PMID- 27271437 TI - [Not Available]. PMID- 27271438 TI - [Not Available]. PMID- 27271439 TI - [Not Available]. PMID- 27271440 TI - [Not Available]. PMID- 27271441 TI - [Not Available]. PMID- 27271442 TI - [Not Available]. PMID- 27271444 TI - [Not Available]. PMID- 27271443 TI - [Not Available]. PMID- 27271445 TI - [Not Available]. PMID- 27271446 TI - [Not Available]. PMID- 27271447 TI - [Not Available]. PMID- 27271448 TI - [Not Available]. PMID- 27271449 TI - [Not Available]. PMID- 27271450 TI - [Prevention of Catheter-Associated Urinary Tract Infections]. AB - With a share of 22.4%, nosocomial urinary tract infections (nUTIs) are among the most frequent infections acquired in hospitals, along with surgical site infections (24.7%), pneumonia (21.5%), clostridium difficile infections (6.6%) and primary sepsis (6%) 1. 80% of all nUTIs are associated with indwelling urinary catheters, with 12-16% of all hospitalised patients and up to 81.8% of all intensive care patients receiving an indwelling urinary catheter during their hospital stay 2 3. Therefore, profound knowledge about the basics of catheter associated nUTIs and the correct management of urinary catheters are of utmost individual and socio-economic importance 4 5. It is estimated that up to 70% of all nUTIs occurring in Germany may be avoided by using appropriate preventative measures 6 7.In 2012, the authors Conway and Larson compared 8 recommendations in English language for the prevention of UTIs and noticed that they have been largely consistent over a period of 30 years 8. Special issues have rarely been addressed in valid studies, and study results are rather heterogeneous. For example, the 2008 SHEA (Society of Hospital Epidemiologists of America) guideline contains only 3 recommendations and 4 prohibitions which are based on more than one randomised controlled clinical study 9 10 11.The confirmed recommendations on the prevention of UTIs are consistent in the following aspects 12 13 14 15 16 17: . Every insertion of a urinary catheter must be based on a well-founded medical indication.. . Well-founded medical indications include acute urinary retention, interventions lasting several hours with a high fluid turnover, surgery involving the urinary tract, the necessity to record fluid turnover especially in critically ill patients, comfort for the dying, facilitating wound healing in the external genitals in the presence of urinary incontinence. Examples of unnecessary use of urinary catheters include prescriptions based on urinary incontinence alone and prolongation of use, e. g. after surgical procedures or after intensive care monitoring/recording has been completed.. . The insertion technique as well as catheter care and the detection of catheter-associated complications must be trained continuously.. . Catheterisation must be performed under sterile precautions.. . Only sterile and closed urinary drainage systems may be used.. . Catheters must be removed as early as possible.. PMID- 27271451 TI - [Not Available]. PMID- 27271452 TI - Markers of calcium and phosphate metabolism and osteopenic syndrome in patients with coronary artery disease. AB - BACKGROUND: The aim of the present study is to assess the level of specific markers of calcium and phosphate metabolism in the development of coronary atherosclerosis in patients with stable coronary artery disease, depending on the severity of osteopenic syndrome. METHODS? In the study 112 male patients aged from 49 to 73 years with verified coronary artery disease were included in the study. Calcium Score was measured using the Agatston Score. Besides, all of them were tested on the serum level of parathyroid hormone, calcitonin, osteocalcin, bone-specific alkaline phosphatase, osteoprotegerin, osteopontin, cathepsin K, estradiol and testosterone. RESULTS? The distribution of patients according to the severity of coronary atherosclerosis using the Syntax Score suggested that the levels of the studied markers did not differ significantly among the patients, despite significant differences in the severity of coronary artery disease. The levels of osteoprotegerin in patients with mild, moderate and severe calcification were significantly lower compared to patients with a zero calcium score. There were no clinical manifestations of osteopenic syndrome in all patients. However, they underwent osteodensitometry with measurement of bone mineral density at the lumbar spine and femoral neck to determine pre-clinical symptoms of bone destruction. Significant increase (P=0.03) in serum levels of osteocalcin was found in patients with radiological evidence of osteoporosis while the other markers did no differ significantly. CONCLUSIONS? We suppose that there is a reciprocal interaction of regulatory vectors with increased calcium deposition in the arterial wall and resorption of bone tissue. PMID- 27271453 TI - Direct analysis in real time-Mass spectrometry (DART-MS) in forensic and security applications. AB - Over the last decade, direct analysis in real time (DART) has emerged as a viable method for fast, easy, and reliable "ambient ionization" for forensic analysis. The ability of DART to generate ions from chemicals that might be present at the scene of a criminal activity, whether they are in the gas, liquid, or solid phase, with limited sample preparation has made the technology a useful analytical tool in numerous forensic applications. This review paper summarizes many of those applications, ranging from the analysis of trace evidence to security applications, with a focus on providing the forensic scientist with a resource for developing their own applications. The most common uses for DART in forensics are in studying seized drugs, drugs of abuse and their metabolites, bulk and detonated explosives, toxic chemicals, chemical warfare agents, inks and dyes, and commercial plant and animal products that have been adulterated for economic gain. This review is meant to complement recent reviews that have described the fundamentals of the ionization mechanism and the general use of DART. We describe a wide range of forensic applications beyond the field of analyzing drugs of abuse, which dominates the literature, including common experimental and data analysis methods. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:171-187, 2018. PMID- 27271454 TI - Serum C-reactive protein and S100A12 concentrations in dogs with hepatic disease. AB - OBJECTIVES: To describe serum C-reactive protein and S100A12 concentrations in dogs with hepatic disease and to determine whether there is a relationship between the concentration of either and the severity of hepatic necroinflammation. METHODS: Serum C-reactive protein and S100A12 concentrations were measured in 46 dogs undergoing hepatic biopsy. Dogs were divided into three groups: congenital portosystemic shunts, chronic hepatitis and hepatic neoplasia. The histological severity of hepatic necroinflammation was scored. RESULTS: C reactive protein and S100A12 concentrations were greater than the upper limit of the reference intervals in 39 and 26% of dogs, respectively. There was no association of disease group with C-reactive protein (P=0.1733) or S100A12 (P=0.1513) concentrations. There was a positive correlation between serum C reactive protein concentration and hepatic necroinflammatory activity (rs =0.428, P=0.006). CLINICAL SIGNIFICANCE: Increased serum C-reactive protein and S100A12 concentrations were observed in a subpopulation of dogs with various types of hepatic diseases, suggesting acute-phase inflammation and activation of phagocytic cells, respectively. Dogs with higher hepatic necroinflammatory activity scores tended to have higher serum C-reactive protein concentrations. Further studies are needed to confirm this finding in a larger group of dogs. PMID- 27271456 TI - The Structure of LiuC, a 3-Hydroxy-3-Methylglutaconyl CoA Dehydratase Involved in Isovaleryl-CoA Biosynthesis in Myxococcus xanthus, Reveals Insights into Specificity and Catalysis. AB - Myxobacteria are able to produce the important metabolite isovaleryl coenzyme A by a route other than leucine degradation. The first step into this pathway is mediated by LiuC, a member of the 3-methylglutaconyl CoA hydratases (MGCH). Here we present crystal structures refined to 2.05 and 1.1 A of LiuC in the apo form and bound to coenzyme A, respectively. By using simulated annealing we modeled the enzyme substrate complex and identified residues potentially involved in substrate binding, specificity, and catalysis. The dehydration of 3-hydroxy-3 methylglutaconyl CoA to 3-methylglutaconyl CoA catalyzed by LiuC involves Glu112 and Glu132 and likely employs the typical crotonase acid-base mechanism. In this, Tyr231 and Arg69 are key players in positioning the substrate to enable catalysis. Surprisingly, LiuC shows higher sequence and structural similarity to human MGCH than to bacterial forms, although they convert the same substrate. This study provides structural insights into the alternative isovaleryl coenzyme A biosynthesis pathway and might open a path for biofuel research, as isovaleryl CoA is a source for isobutene, a precursor for renewable fuels and chemicals. PMID- 27271457 TI - Erratum: Observation of an evolving magnetic flux rope before and during a solar eruption. PMID- 27271455 TI - Effect of the INSIGHT Responsive Parenting Intervention on Rapid Infant Weight Gain and Overweight Status at Age 1 Year: A Randomized Clinical Trial. AB - IMPORTANCE: Rapid infant weight gain is associated with later obesity, but interventions to prevent rapid infant growth and reduce risk for overweight status in infancy are lacking. OBJECTIVE: To examine the effect of a responsive parenting (RP) intervention on infant weight gain between birth and 28 weeks and overweight status at age 1 year. DESIGN, SETTING, AND PARTICIPANTS: The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) study is an ongoing randomized clinical trial comparing an RP intervention designed to prevent childhood obesity with a safety control. The study includes primiparous mother-newborn dyads (n = 291) and was conducted at the Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, in addition to home visits. Enrollment was initiated in January 2012, and evaluable population analyses for this study were conducted between April 2015 and November 2015. INTERVENTIONS: At 2 weeks post partum, initial intervention materials appropriate to the assigned treatment group were mailed to the participant's home. Research nurses conducted home visits at 3 weeks, 16 weeks, 28 weeks, and 40 weeks, and a research center visit occurred at 1 year. The Intervention Nurses Start Infants Growing on Healthy Trajectories curriculum included messages about infant feeding, sleep hygiene, active social play, emotion regulation, and growth record education. The control group received a developmentally appropriate home safety intervention also delivered by nurse home visitors. MAIN OUTCOMES AND MEASURES: Conditional weight gain from birth to 28 weeks was calculated. General linear models examined intervention effect on conditional weight gain. The intervention's effect on infant weight-for-length percentiles was tested using analysis of variance. Logistic regression compared the odds of overweight status (weight for length >=95th percentile) at 1 year as a function of conditional weight gain. RESULTS: Of the mothers included in the study, 246 were white (88%), 260 were non-Hispanic (93%), 210 were married (75%), and 201 were working full time (72%) at time of enrollment. The mean conditional weight gain score was lower among infants in the RP group compared with the control group (-0.18; 95% CI, -0.36 to -0.001), reflecting that the RP infants gained weight more slowly than control group infants (0.18; 95% CI, 0.02-0.34); this effect did not differ by feeding mode (predominantly fed breast milk or not). Infants in the RP group also had lower mean weight-for-length percentiles at 1 year than infants in the control group (57.5%; 95% CI, 52.56%-62.37% vs 64.4%; 95% CI, 59.94%-69.26%; P = .04) and were less likely to be overweight at age 1 year (5.5% vs 12.7%; P = .05). CONCLUSIONS AND RELEVANCE: An RP intervention is associated with reduced rapid weight gain during the first 6 months after birth and overweight status at age 1 year. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01167270. PMID- 27271460 TI - Ring-Shaped Phosphinoamido-Magnesium-Hydride Complexes: Syntheses, Structures, Reactivity, and Catalysis. AB - A series of magnesium(II) complexes bearing the sterically demanding phosphinoamide ligand, L(-) =Ph2 PNDip(-) , Dip=2,6-diisopropylphenyl, including heteroleptic magnesium alkyl and hydride complexes are described. The ligand geometry enforces various novel ring and cluster geometries for the heteroleptic compounds. We have studied the stoichiometric reactivity of [(LMgH)4 ] towards unsaturated substrates, and investigated catalytic hydroborations and hydrosilylations of ketones and pyridines. We found that hydroborations of two ketones with pinacolborane using various Mg precatalysts is very rapid at room temperature with very low catalyst loadings, and ketone hydrosilylation using phenylsilane is rapid at 70 degrees C. Our studies point to an insertion/sigma bond metathesis catalytic cycle of an in situ formed "MgH2 " active species. PMID- 27271458 TI - Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes. AB - Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution. We thus propose a new graph theory approach that focuses on the correlation influence between selected brain regions, entitled Dependency Network Analysis (DEPNA). Partial correlations are used to quantify the level of influence of each node during task performance. As a proof of concept, we conducted the DEPNA on simulated datasets and on two empirical motor and working memory fMRI tasks. The simulations revealed that the DEPNA correctly captures the network's hierarchy of influence. Applying DEPNA to the functional tasks reveals the dynamics between specific nodes as would be expected from prior knowledge. To conclude, we demonstrate that DEPNA can capture the most influencing nodes in the network, as they emerge during specific cognitive processes. This ability opens a new horizon for example in delineating critical nodes for specific clinical interventions. PMID- 27271462 TI - Organizational stress management interventions: Is it the singer not the song? PMID- 27271461 TI - Freehand three-dimensional ultrasound to assess semitendinosus muscle morphology. AB - In several neurological disorders and muscle injuries, morphological changes of the m. semitendinosus (ST) are presumed to contribute to movement limitations around the knee. Freehand three-dimensional (3D) ultrasound (US), using position tracking of two-dimensional US images to reconstruct a 3D voxel array, can be used to assess muscle morphology in vivo. The aims of this study were: (i) to introduce a newly developed 3D US protocol for ST; and (ii) provide a first comparison of morphological characteristics determined by 3D US with those measured on dissected cadaveric muscles. Morphological characteristics of ST (e.g. muscle belly length, tendon length, fascicle length and whole muscle volume, and volumes of both compartments) were assessed in six cadavers using a 3D US protocol. Subsequently, ST muscles were removed from the body to measure the same morphological characteristics. Mean differences between morphological characteristics measured by 3D US and after dissection were smaller than 10%. Intra-class correlation coefficients (ICCs) were higher than 0.75 for all variables except for the lengths of proximal fascicles (ICC = 0.58). Measurement of the volume of proximal compartment by 3D US was not feasible, due to low US image quality proximally. We conclude that the presented 3D US protocol allows for reasonably accurate measurements of key morphological characteristics of ST muscle. PMID- 27271463 TI - Enhanced Singlet Oxygen Generation in Oxidized Graphitic Carbon Nitride for Organic Synthesis. AB - Experimental data reveal that the incorporation of carbonyl groups into polymer matrix can significantly enhance singlet oxygen ((1) O2 ) generation and suppress production of other reactive oxygen species. Excitonic processes investigated by phosphorescence spectroscopy reveal enhanced triplet-exciton generation in the modified g-C3 N4 , which facilitate (1) O2 generation through an energy transfer process. Benefiting from this, the modified g-C3 N4 shows excellent conversion and selectivity in organic synthesis. PMID- 27271464 TI - Erratum to: Predation of a squirrel monkey (Saimiri sciureus) by an Amazon tree boa (Corallus hortulanus): even small boids may be a potential threat to small bodied platyrrhines. PMID- 27271465 TI - Enhancement of toughness and wear resistance in boron nitride nanoplatelet (BNNP) reinforced Si3N4 nanocomposites. AB - Ceramics have superior hardness, strength and corrosion resistance, but are also associated with poor toughness. Here, we propose the boron nitride nanoplatelet (BNNP) as a novel toughening reinforcement component to ceramics with outstanding mechanical properties and high-temperature stability. We used a planetary ball milling process to exfoliate BNNPs in a scalable manner and functionalizes them with polystyrene sulfonate. Non-covalently functionalized BNNPs were homogeneously dispersed with Si3N4 powders using a surfactant and then consolidated by hot pressing. The fracture toughness of the BNNP/Si3N4 nanocomposite increased by as much as 24.7% with 2 vol.% of BNNPs. Furthermore, BNNPs enhanced strength (9.4%) and the tribological properties (26.7%) of the ceramic matrix. Microstructural analyzes have shown that the toughening mechanisms are combinations of the pull-out, crack bridging, branching and blunting mechanisms. PMID- 27271466 TI - Synthesis of alpha-MoC1-x Nanoparticles with a Surface-Modified SBA-15 Hard Template: Determination of Structure-Function Relationships in Acetic Acid Deoxygenation. AB - Surface modification of mesoporous SBA-15 silica generated a hydrophobic environment for a molybdenum diamine (Mo-diamine) precursor solution, enabling direct growth of isolated 1.9+/-0.4 nm alpha-MoC1-x nanoparticles (NPs) inside the pores of the support. The resulting NP catalysts are bifunctional, and compared to bulk alpha-MoC1-x and beta-Mo2 C, the NPs exhibit a greater acid site:H-site ratio and a fraction of stronger acid sites. The greater acid-site:H site ratio results in higher decarbonylation (DCO) selectivity during acetic acid hydrodeoxygenation (HDO) reactions, and the stronger acid sites lead to higher activity and ketonization (KET) selectivity at high temperatures. The hard templating synthetic method could be a versatile route toward carbide NPs of varying size, composition, and phase, on a range of mesoporous oxide supports. PMID- 27271468 TI - Contribution of iron and protein contents from rat brain subcellular fractions to MR phase imaging. AB - PURPOSE: Investigation of magnetic susceptibility and chemical exchange as sources of MRI phase contrast between gray and white matter resulting from protein and iron content from subcellular fractions. METHODS: This study analyzes the iron and macromolecule content of different subcellular fractions from rat brain and their relation to the water-resonance frequency by NMR spectroscopy. Additionally, the contributions of susceptibility and exchange were determined with different NMR reference substances. RESULTS: Only weak correlations between iron (r = 0.4318, P = 0.76) or protein content (r = 0.4704, P = 0.70) and frequency shift were observed. After membrane depletion, the correlation for iron increased to r = -0.9006 (P = 0.0009), whereas the shift relative to protein content increased much less (r = -0.4982, P = 0.64). Exchange-driven frequency shifts were 1.283 ppb/(mg/ml) for myelin and 0.775 ppb/(mg/ml) for synaptosomes; susceptibility-driven shifts were -1.209 ppb/(mg/ml) for myelin and -0.368 ppb/(mg/ml) for synaptosomes. The ratios between susceptibility and exchange differ significantly from simple protein solutions. CONCLUSIONS: As a result of counteracting susceptibility and exchange and increased relative shifts in membrane-depleted fractions, we conclude that tissue microstructure accounts more for the in vivo phase contrast than in the situation of homogenized tissue. Thus, membranes may generate much of the in vivo MR phase contrast resulting from anisotropy. Magn Reson Med 77:2028-2039, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 27271469 TI - Laparoscopic repair of irreducible femoral hernia containing the fallopian tube alone: a case report. AB - BACKGROUND: We offer the first report of laparoscopic repair of an irreducible femoral hernia containing the fallopian tube alone. CASE PRESENTATION: An 84-year old woman presented with a 2-week history of a right groin mass with no abdominal symptoms. The mass was located below the inguinal ligament but showed no redness or tenderness. Abdominal computed tomography demonstrated a 4 * 3-cm cystic mass and enhanced cord-like structure in the right groin area. Hernia contents were considered potentially associated with the appendix, and right femoral hernia incarceration was diagnosed. We performed emergency surgery using a laparoscopic approach, revealing an irreducible femoral hernia containing the right fallopian tube, which was reduced laparoscopically. The reduced fallopian tube showed no ischemic changes, obviating the need for resection. No other abdominal organs such as the ovary, fimbriae of the fallopian tube, or appendix were incarcerated. We repaired the femoral hernia laparoscopically using a transabdominal preperitoneal approach with a mesh. CONCLUSIONS: A laparoscopic approach offers ready and accurate confirmation of incarcerated or irreducible organs, rapid recovery, and favorable cosmesis and should therefore be considered for the treatment of incarcerated or irreducible femoral hernia. PMID- 27271467 TI - Influence of Age on Ocular Biomechanical Properties in a Canine Glaucoma Model with ADAMTS10 Mutation. AB - Soft tissue often displays marked age-associated stiffening. This study aims to investigate how age affects scleral biomechanical properties in a canine glaucoma model with ADAMTS10 mutation, whose extracellular matrix is concomitantly influenced by the mutation and an increased mechanical load from an early age. Biomechanical data was acquired from ADAMTS10-mutant dogs (n = 10, 21 to 131 months) and normal dogs (n = 5, 69 to 113 months). Infusion testing was first performed in the whole globes to measure ocular rigidity. After infusion experiments, the corneas were immediately trephined to prepare scleral shells that were mounted on a pressurization chamber to measure strains in the posterior sclera using an inflation testing protocol. Dynamic viscoelastic mechanical testing was then performed on dissected posterior scleral strips and the data were combined with those reported earlier by our group from the same animal model (Palko et al, IOVS 2013). The association between age and scleral biomechanical properties was evaluated using multivariate linear regression. The relationships between scleral properties and the mean and last measured intraocular pressure (IOP) were also evaluated. Our results showed that age was positively associated with complex modulus (p<0.001) and negatively associated with loss tangent (p<0.001) in both the affected and the normal groups, suggesting an increased stiffness and decreased mechanical damping with age. The regression slopes were not different between the groups, although the complex modulus was significantly lower in the affected group (p = 0.041). The posterior circumferential tangential strain was negatively correlated with complex modulus (R = -0.744, p = 0.006) showing consistent mechanical evaluation between the testing methods. Normalized ocular rigidity was negatively correlated with the last IOP in the affected group (p = 0.003). Despite a mutation that affects the extracellular matrix and a chronic IOP elevation in the affected dogs, age-associated scleral stiffening and loss of mechanical damping were still prominent and had a similar rate of change as in the normal dogs. PMID- 27271470 TI - Early gastric cancer metastasizing to the rectum, possibly via a hematogenous route: a case report and review of literature. AB - BACKGROUND: The most common pattern of recurrence of gastric cancer (GC) is peritoneal dissemination. However, rectal metastasis via hematogenous or lymphatic spread is exceedingly rare. We present a case of a 65-year-old man with an intramucosal GC who developed a rectal recurrence, possibly via a hematogenous route. CASE PRESENTATION: A 65-year-old man underwent curative endoscopic submucosal dissections for the intramucosal GCs at the anterior wall of the fornix twice. The third GC at the similar location was treated by radical laparoscopic proximal gastrectomy; microscopic examination revealed well differentiated tubular adenocarcinoma confined to the lamina propria mucosae (T1aN0M0, stage IA). Follow-up colonoscopy revealed a 30-mm submucosal mass in the rectal wall 2 years later, and a metastasis of gastric origin was suspected histopathologically. After a staging laparoscopy confirmed the absence of findings suggestive of serosal involvement or peritoneal dissemination, including negative peritoneal washing cytology, a laparoscopic low anterior resection with lymph node dissection was performed. Microscopically, the tumor was found to mainly be located in the submucosal layer and showed features of moderately differentiated tubular adenocarcinoma. The serosal surface was free of disseminated tumor. Lymph node metastases were identified. Immunohistochemically, there were foci of carcinoma cells that were positive for cytokeratin 20; however, they were negative for cytokeratin 7. Negative staining for caudal-type homeobox 2, a transcription factor indicating goblet cell differentiation, combined with absence of intramucosal carcinoma in the rectal mucosa, suggested a diagnosis of metastatic adenocarcinoma of gastric origin. The absence of evidence of peritoneal dissemination suggested hematogenous or lymphatic spread. CONCLUSION: Although rectal metastasis from GC, particularly when attributable to hematologic or lymphatic metastasis, is very rare, metastatic gastric adenocarcinoma should be considered as a differential diagnosis for patients who present with a rectal tumor and a past history of GC, even if it is an early GC. PMID- 27271471 TI - An injectable extracellular matrix for the reconstruction of epidural fat and the prevention of epidural fibrosis. AB - Extensive epidural fibrosis is a common complication following spinal surgery and can cause pain and limited mobility. In the present study, a novel biomimetic approach was developed to prevent postsurgical adhesion of the dura. We aimed to reconstruct epidural fat, which prevents scar-tissue adhesion, through the development of an injectable decellularized adipose matrix (DAM)-containing hyaluronic acid (HA) hydrogel loaded with adipose stromal cells (ASCs). Injectable DAM was prepared from porcine adipose tissue by four freeze-thaw cycles with subsequent pepsin digestion. Residual analyses confirmed the efficacy of detergent-free decellularization, while most sulfated glycosaminoglycans and collagen were preserved. The Transwell migration assay demonstrated the anti infiltrative property of the DAM-containing HA hydrogel. After 14 d of 3D culture, the DAM-containing HA hydrogel showed inductive potential in the adipogenic differentiation of ASCs. For an in vivo study, the ASC-loaded DAM containing HA hydrogel (DAM/ASC-incorporated HA hydrogel) was injected into adult laminectomized male rats, and the results were assessed by microscopic histological examination. The in vivo data indicated that HA hydrogel, DAM, and ASCs were all required for the ability of the engineered fat tissue to block the invasion of the fibrous tissue. Our results suggested that this injectable DAM/ASC-incorporated HA hydrogel has potential applications in minimally invasive surgery for soft-tissue reconstruction and epidural fibrosis prevention. PMID- 27271472 TI - Validation of the RisingSun RS-651 Blood Pressure Monitor Based on Auscultation in Adults According to the ANSI/AAMI/ISO 81060-2:2013 Standard. AB - This study validated the RisingSun RS-651 blood pressure (BP) monitor based on auscultation in adults according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2:2013 standard. The RS-651 device was evaluated in a study of 97 participants. The same arm simultaneous method, as defined in the ANSI/AAMI/ISO standard, was used. The mean differences+/-standard deviation for criterion 1 were 0.8+/-2.3 mm Hg for systolic BP (SBP) and -0.1+/-2.9 mm Hg for diastolic BP (DBP). Analysis for criterion 2 resulted in values of 0.8+/-1.5 mm Hg for SBP and -0.1+/-2.1 mm Hg for DBP. All of the data fulfilled the ANSI/AAMI/ISO 81060 2:2013 standard requirements to pass the validation. The RisingSun RS-651 device can be recommended for both clinical and self/home use in adults according to the ANSI/AAMI/ISO 81060-2:2013 standard. PMID- 27271473 TI - Chemerin is not associated with subclinical atherosclerosis markers in prediabetes and diabetes. AB - OBJECTIVE: Chemerin is a novel adipokine that is correlated with adipocyte differentiation, glucose metabolism, and inflammation. We aimed to investigate the relation between serum chemerin level and subclinical atherosclerosis markers as exemplified by brachial artery pulse wave velocity (baPWV), carotid intima media thickness (CIMT), epicardial fat thickness (EFT), and carotid plaque presence in diabetes and prediabetes. METHODS: Age-, body mass index (BMI)-, and gender-matched patients with type 2 DM (n=30), prediabetes (n=25), and normal glucose tolerance (n=25) were included in this cross-sectional study. Serum chemerin level, lipid parameters, glucose metabolism marker, baPWV, CIMT, EFT, and anthropometric were recorded. The independent risk factors for atherosclerosis markers were determined by linear and/or multiple logistic regression analysis. RESULTS: baPWV and carotid plaque presence were higher in the diabetes group than in prediabetes and control groups (p=0.039 and p=0.035 respectively), whereas serum chemerin levels were similar among groups (p=0.338). Chemerin levels were not correlated with PWV, CIMT, and epicardial fat thickness overall or in the subgroups. Overall and in the diabetes group, chemerin levels were positively correlated with the key components of metabolic syndrome as BMI, total body fat percentage, waist circumference, triglyceride, and systolic and diastolic blood pressure (BP). After adjusting for age, gender, and BMI, only the association between chemerin and systolic BP remained significant. Chemerin was not found as an independent risk factor for predicting atherosclerosis in diabetes and prediabetes. CONCLUSION: Chemerin is not a predictive marker for atherosclerosis in diabetes and prediabetes, but correlates well with key aspects of the metabolic syndrome particularly in diabetes. PMID- 27271474 TI - Echocardiographic assessment of right ventricular functions in healthy subjects who migrated from the sea level to a moderate altitude. AB - OBJECTIVE: The aim of this study was to evaluate right ventricle (RV) functions using echocardiography in healthy subjects who migrated from the sea level to moderate altitude (1890 m). METHODS: The prospective observational in this study population consisted of 33 healthy subjects (23 men; mean age 20.4+/-3.2 years) who migrated from the sea level to a moderate altitude (Erzurum city centre, 1890 m above sea level) for long-term stay. Subjects underwent echocardiographic evaluation within the first 48 h of exposure to the moderate altitude and at the sixth month of arrival. Conventional echocardiographic parameters such as RV sizes and areas, systolic, and diastolic functional indices [fractional area change (FAC), tricuspid flow velocities, myocardial performance index (MPI), and tricuspid annular plane systolic excursion (TAPSE)] were obtained. Systolic (S) and diastolic (E', A') velocities were acquired from the apical fourchamber view using tissue Doppler imaging. Kolmogorov-Smirnov test, student's t-test, Wilcoxon test, and chi-square test were used in this study. RESULTS: There were no significant changes in RV size, FAC, MPI, TAPSE, inferior inspiratory vena cava collapse, tricuspid E velocity, and tricuspid annulus E' velocity. Compared with the baseline, there was a significant increase in mean pulmonary artery pressure (p=0.001); RV end systolic area (p=0.014); right atrial end diastolic area (p=0.021); tricuspid A velocity (p=0.013); tricuspid annulus S and A' velocity (p=0.031 and p=0.006, respectively); and RV free wall S, E', and A' velocity (p=0.007, p<0.001, and p=0.007 respectively) at the sixth month. Also, there was a significant decrease in tricuspid E/A ratio (1.61+/-0.3 vs. 1.45+/-0.2, p=0.038) and tricuspid annulus E'/A' ratio (1.52+/-0.5 vs. 1.23+/-0.4, p=0.002) at the sixth month. CONCLUSION: Our study revealed that right ventricular diastolic function was altered while the systolic function was preserved in healthy subjects who migrated from the sea level to a moderate altitude. PMID- 27271475 TI - Age and gender differences in Framingham risk score and metabolic syndrome in psoriasis patients: A cross-sectional study in the Turkish population. AB - OBJECTIVE: Psoriasis is associated with an increased frequency of cardiovascular risk factors. Metabolic syndrome (MS) and the Framingham risk score (FRS) are two different algorithms for evaluating cardiovascular risk. They include different features: waist circumference measurement is included in the MS criteria, whereas smoking, age, and gender are questioned in FRS. This study aimed to evaluate the frequency of MS and FRS in psoriasis patients compared with a control group and investigate the differences between MS and FRS. METHODS: This was a cross sectional study involving 300 psoriasis patients and 177 controls. MS, FRS, and disease severity were evaluated. RESULTS: The frequency of MS was higher in females with psoriasis than in those in the control group (p=0.019). Females in the psoriasis group were more obese than those in the control group (p=0.036). FRS significantly differed between the patients and controls of age >60 years (p=0.006). The risk of hypertension in current and past smokers was higher in the psoriasis patients (OR=2.07 and 2.32-2.48, respectively) than in the control group. There was no statistically significant relationship among MS, FRS, and psoriasis severity (p>0.05). CONCLUSION: The results of this study support the evaluation of cardiovascular risk assessment in female psoriasis patients with MS and in male and elderly psoriasis patients with FRS. PMID- 27271476 TI - The first six-month clinical outcomes and risk factors associated with high on treatment platelet reactivity of clopidogrel in patients undergoing coronary interventions. AB - OBJECTIVE: This study attempted to fill the gaps in evidence related to response to clopidogrel treatment in the Turkish population. The study aimed to determine the prevalence, associated risk factors, and clinical outcomes of high on treatment platelet reactivity (HTPR) of clopidogrel in patients undergoing percutaneous coronary intervention (PCI) in a tertiary cardiovascular hospital in Turkey. METHODS: In this prospective studied a total of 1.238 patients undergoing PCI were included in the present study. Blood samples were analyzed using a Multiplate analyzer. All patients were examined in the outpatient clinics at the end of the first and sixth months for recording drug therapy compliance and study endpoints. RESULTS: Among the study population, 324 (30.2%) patients were found to have HTPR (mean age 58.03+/-11.88 years, 71.7% men). The incidence of HTPR was higher amongst females than amongst males (38.3% vs. 27%, p=0.010). Hypertension and diabetes mellitus were more frequently observed in the HTPR group (57.7% vs. 48.7%, p=0.004; 35% vs. 29.1%, p=0.040, respectively). When the recorded data were analyzed using multinomial regression analysis, hypertension, hemoglobin level, platelet, lymphocyte, and eosinophil count were independently associated with HTPR. CONCLUSION: On the basis of the results obtained from our study, we conclude that 30.2% of the Turkish population has HTPR. Our results also led us to believe that hypertension is an associated risk factor and decreased hemoglobin level as well as increased platelet counts are laboratory parameters that are strongly associated with the presence of HTPR. However, no differences were observed with regard to cardiovascular mortality and stent thrombosis. PMID- 27271478 TI - Determinants of prevalence, awareness, treatment and control of high LDL-C in Turkey. AB - OBJECTIVE: High blood cholesterol is one of the main modifiable risk factors for cardiovascular diseases (CVDs). The aim of the study is to determine the factors associated with the prevalence, awareness, treatment, and control of high "low density lipoprotein-cholesterol" (LDL-C) among adults aged >=20 years in Turkey. METHODS: We used data from Chronic Diseases and Risk Factors Survey conducted in 2011-2012. The presence of high LDL-C, lipid-lowering treatment eligibility, and achievement of target LDL-C were defined according to the third Adult Treatment Panel guidelines on treatment of high cholesterol. Multivariate logistic regression analyses were performed to determine the associations between participant characteristics and high LDL-C prevalence, awareness, treatment, and control. RESULTS: Framingham risk score categorization was performed for 13121 individuals aged >=20 years. Approximately, 28% of the participants presented with high LDL-C. Among those with high LDL-C, 55.8% were aware of their situation; among those aware of high LDL-C, 46.9% were receiving lipidlowering medication, and 50.6% of individuals who were receiving treatment achieved target LDL-C levels on the basis of their coronary heart disease (CHD) risk. Control of high LDL-C was negatively associated with the presence of diabetes mellitus (odds ratio: 0.36, 95% CI:0.27-0.49, p<0.001). CONCLUSION: Despite the high awareness rates, there was a high proportion of adults who did not receive treatment or achieve recommended levels of LDL-C during treatment. The low treatment and control levels among individuals based on their CHD risk levels call for a better application of recommendations regarding personal preventive measures and treatments in Turkey. PMID- 27271477 TI - Assessment of 25-OH vitamin D levels and abnormal blood pressure response in female patients with cardiac syndrome X. AB - OBJECTIVE: Vitamin D deficiency is associated with coronary artery disease, hypertension, heart failure, endothelial dysfunction, and metabolic syndrome. The pathophysiology of cardiac syndrome X (CSX) involves many pathways that are influenced by vitamin D levels. This study aimed to investigate the relationship between vitamin D deficiency and abnormal blood pressure response to exercise in patients with CSX. METHODS: This was a cross-sectional and observational study. Fifty females with normal epicardial coronary arteries who presented with typical symptoms of rest or effort angina and 41 healthy age-matched female controls, were included. Patients with cardiomyopathy, severe valvular disease, congenital heart disease, and left ventricular hypertrophy were excluded. All patients underwent stress electrocardiography examination and 25-hydroxy (OH) vitamin D level measurements. RESULTS: Levels of 25-OH vitamin D were significantly lower in CSX patients (9.8+/-7.3 ng/mL vs. 18.1+/-7.9 ng/mL; p<0.001). Systolic blood pressure (SBP) (188+/-15 mm Hg vs. 179+/-17 mm Hg; p=0.013) and diastolic blood pressure (DBP) (98+/-9 mm Hg vs. 88+/-9 mm Hg; p<0.001) during peak exercise were higher in CSX patients. Levels of 25-OH vitamin D were negatively correlated with peak SBP (r=-0.310, p=0.004) and peak DBP (r=-0.535, p<0.001) during exercise. To discard the multicollinearity problem, two different models were used for multivariate analyses. In the first model, metabolic equivalents (METs) (p=0.003) and 25-OH vitamin D levels (p=0.001) were independent predictors. METs (p=0.007), 25-OH vitamin D levels (p=0.008), and peak DBP were determined as independent predictors in the second multivariate model. CONCLUSION: In patients with CSX, 25 OH vitamin D levels were lower than those in controls; moreover, 25-OH vitamin D deficiency was also associated with higher levels of peak DBP during exercise. PMID- 27271480 TI - Hypertonic salt solution for peri-operative fluid management. AB - BACKGROUND: Fluid excess may place people undergoing surgery at risk for various complications. Hypertonic salt solution (HS) maintains intravascular volume with less intravenous fluid than isotonic salt (IS) solutions, but may increase serum sodium. This review was published in 2010 and updated in 2016. OBJECTIVES: To determine the benefits and harms of HS versus IS solutions administered for fluid resuscitation to people undergoing surgery. SEARCH METHODS: In this updated review we have searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2016); MEDLINE (January 1966 to April 2016); EMBASE (January 1980 to April 2016); LILACS (January 1982 to April 2016) and CINAHL (January 1982 to April 2016) without language restrictions. We conducted the original search on April 30th, 2007, and reran it on April 8th, 2016. SELECTION CRITERIA: We have included randomized clinical trials (RCTs) comparing HS to IS in people undergoing surgery, irrespective of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS: Two independent review authors read studies that met our selection criteria. We collected study information and data using a data collection sheet with predefined parameters. We have assessed the impact of HS administration on mortality, organ failure, fluid balance, serum sodium, serum osmolarity, diuresis and physiologic measures of cardiovascular function. We have pooled the data using the mean difference (MD) for continuous outcomes. We evaluated heterogeneity between studies by I2 percentage. We consider studies with an I2 of 0% to 30% to have no or little heterogeneity, 30% to 60% as having moderate heterogeneity, and more than 60% as having high heterogeneity. In studies with low heterogeneity we have used a fixed-effect model, and a random effects model for studies with moderate to high heterogeneity. MAIN RESULTS: We have included 18 studies with 1087 participants of whom 545 received HS compared to 542 who received IS. All participants were over 18 years of age and all trials excluded high-risk patients (ASA IV). All trials assessed haematological parameters peri-operatively and up to three days post-operatively.There were three (< 1%) deaths reported in the IS group and four (< 1%) in the HS group, as assessed at 90 days in one study. There were no reports of serious adverse events. Most participants were in a positive fluid balance postoperatively (4.4 L IS and 2.5 L HS), with the excess significantly less in HS participants (MD -1.92 L, 95% confidence interval (CI) -2.61 to -1.22 L; P < 0.00001). IS participants received a mean volume of 2.4 L and HS participants received 1.49 L, significantly less fluid than IS-treated participants (MD -0.91 L, 95% CI -1.24 to -0.59 L; P < 0.00001). The maximum average serum sodium ranged between 138.5 and 159 in HS groups compared to between 136 and 143 meq/L in the IS groups. The maximum serum sodium was significantly higher in HS participants (MD 7.73, 95% CI 5.84 to 9.62; P < 0.00001), although the level remained within normal limits (136 to 146 meq/L).A high degree of heterogeneity appeared to be related to considerable differences in the dose of HS between studies. The quality of the evidence for the outcomes reported ranged from high to very low. The risk of bias for many of the studies could not be determined for performance and detection bias, criteria that we assess as likely to impact the study outcomes. AUTHORS' CONCLUSIONS: HS reduces the volume of intravenous fluid required to maintain people undergoing surgery but transiently increases serum sodium. It is not known if HS affects survival and morbidity, but this should be examined in randomized controlled trials that are designed and powered to test these outcomes. PMID- 27271479 TI - Heterogeneous Nuclear Ribonucleoprotein L is required for the survival and functional integrity of murine hematopoietic stem cells. AB - The proliferation and survival of hematopoietic stem cells (HSCs) has to be strictly coordinated to ensure the timely production of all blood cells. Here we report that the splice factor and RNA binding protein hnRNP L (heterogeneous nuclear ribonucleoprotein L) is required for hematopoiesis, since its genetic ablation in mice reduces almost all blood cell lineages and causes premature death of the animals. In agreement with this, we observed that hnRNP L deficient HSCs lack both the ability to self-renew and foster hematopoietic differentiation in transplanted hosts. They also display mitochondrial dysfunction, elevated levels of gammaH2AX, are Annexin V positive and incorporate propidium iodide indicating that they undergo cell death. Lin(-)c-Kit(+) fetal liver cells from hnRNP L deficient mice show high p53 protein levels and up-regulation of p53 target genes. In addition, cells lacking hnRNP L up-regulated the expression of the death receptors TrailR2 and CD95/Fas and show Caspase-3, Caspase-8 and Parp cleavage. Treatment with the pan-caspase inhibitor Z-VAD-fmk, but not the deletion of p53, restored cell survival in hnRNP L deficient cells. Our data suggest that hnRNP L is critical for the survival and functional integrity of HSCs by restricting the activation of caspase-dependent death receptor pathways. PMID- 27271481 TI - Spatializing 6,000 years of global urbanization from 3700 BC to AD 2000. AB - How were cities distributed globally in the past? How many people lived in these cities? How did cities influence their local and regional environments? In order to understand the current era of urbanization, we must understand long-term historical urbanization trends and patterns. However, to date there is no comprehensive record of spatially explicit, historic, city-level population data at the global scale. Here, we developed the first spatially explicit dataset of urban settlements from 3700 BC to AD 2000, by digitizing, transcribing, and geocoding historical, archaeological, and census-based urban population data previously published in tabular form by Chandler and Modelski. The dataset creation process also required data cleaning and harmonization procedures to make the data internally consistent. Additionally, we created a reliability ranking for each geocoded location to assess the geographic uncertainty of each data point. The dataset provides the first spatially explicit archive of the location and size of urban populations over the last 6,000 years and can contribute to an improved understanding of contemporary and historical urbanization trends. PMID- 27271482 TI - Efficacy and safety of erythrocytapheresis and low-dose erythropoietin for treatment of hemochromatosis. AB - BACKGROUND: The aim of this study was to determine retrospectively the efficacy of combined therapy using erythropoietin (EPO) and erythrocytapheresis (EA) in patients with hereditary hemochromatosis (HH) who did not tolerate phlebotomy. PATIENTS AND METHODS: Twenty patients (age range, 43-74 years) with genetically confirmed HH had received low-dose EPO (4,000 IU) in accordance to the patient's hemoglobin levels between each EA session. Laboratory parameters including hemoglobin, ferritin, transferrin, and iron were measured at regular intervals. RESULTS: Anemia did not occur in a single patient and no serious side effects were observed. Combined treatment with EPO and EA was well tolerated, and all 18 patients who suffered from fatigue prior to therapy recovered. Median ferritin values were 678.5 ng/L before treatment and 145 ng/L after treatment. CONCLUSION: EA in combination with EPO is safe and effective in treating patients with HH. Prospective studies comparing this therapeutic option to phlebotomy are warranted. J. Clin. Apheresis 32:170-174, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27271483 TI - Seroma-associated anaplastic large-cell lymphoma arising on the background of subcutaneous calcinosis: beyond breast implants. PMID- 27271484 TI - Assessing the transport rate of hyperpolarized pyruvate and lactate from the intra- to the extracellular space. AB - The use of [1-(13) C]pyruvate hyperpolarized by means of dynamic nuclear polarization provides a direct way to track the metabolic transformations of this metabolite in vivo and in cell cultures. The identification of the intra- and extracellular contributions to the (13) C NMR resonances is not straightforward. In order to obtain information about the rate of pyruvate and lactate transport through the cellular membrane, we set up a method that relies on the sudden 'quenching' of the extracellular metabolites' signal. The paramagnetic Gd tetraazacyclododecane triacetic acid (Gd-DO3A) complex was used to dramatically decrease the longitudinal relaxation time constants of the (13) C-carboxylate resonances of both pyruvate and lactate. When Gd-DO3A was added to an MCF-7 cellular culture, which had previously received a dose of hyperpolarized [1-(13) C]pyruvate, the contributions of the extracellular pyruvate and lactate signals were deleted. From the analysis of the decay curves of the (13) C-carboxylate resonances of pyruvate and lactate it was possible to extract information about the exchange rate of the two metabolites across the cellular membrane. In particular, it was found that, in the reported experimental conditions, the lactate transport from the intra- to the extracellular space is not much lower than the rate of lactate formation. The method reported herein is non-destructive and it could be translated to in vivo studies. It opens a route for the use of hyperpolarized pyruvate to assess altered activity of carboxylate transporter proteins that may occur in pathological conditions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271485 TI - High-pressure phase transitions in rubidium and caesium hydroxides. AB - A computational investigation of the high-pressure phase sequence of the heaviest alkali hydroxides, RbOH and CsOH, shows that the phase diagram of both compounds is richer than hitherto thought. First-principles calculations suggest, based on energetics and comparisons to experimental diffraction and spectroscopy signatures, that the high-pressure phase RbOH-VI, stable above 6 GPa in experiment, should be assigned the KOH-VI structure type, and features localised hydrogen-bonded (OH)4 units. Meanwhile, a new high-pressure phase CsOH-VII is predicted to be stable above 10 GPa in an isosymmetric phase transition that, like RbOH-VI, marks the transition from layered to three-dimensional network structures under increased compression. Both new phases highlight an unexpected flexibility of hydrogen bond network formation in a series of compounds that seemingly only vary in the cation size, and potential consequences for similar systems, such as water-carrying minerals, are discussed briefly. PMID- 27271486 TI - Chronic Traumatic Encephalopathy in a 25-Year-Old Athlete-Distribution of Lesions. PMID- 27271487 TI - Understanding Work Experiences of People with Inflammatory Bowel Disease. AB - BACKGROUND: People with inflammatory bowel disease (IBD) are at increased risk for unemployment and work absenteeism over the course of their adult lives. However, little is known about the firsthand experiences of people living with the disease regarding perceived barriers, facilitators, and strategies for navigating work roles. METHODS: In this qualitative study, participants were purposefully recruited from 2 existing IBD cohort study samples. Recruitment strategies aimed for diversity in age, sex, and disease type, duration, and symptom activity. In-depth interviews sought perspectives of living with IBD. Data were analyzed using inductive qualitative methods. RESULTS: Forty-five people currently or previously in the workforce participated; 51% were female. The mean age was 45.4 years (SD = 16.1; range = 21-73 years). Mean IBD duration was 10.9 years (SD = 6.3). Participants had a broad range of experiences in adapting to work roles. IBD symptoms and treatments interacted with other personal and environmental factors to shape the experiences of work. Experiences were shaped by: (1) personal health and well-being, (2) personal values, beliefs, and knowledge, (3) job characteristics, (4) workplace physical environment, (5) workplace culture, and (6) financial factors. Participants identified personal strategies and environmental supports that assisted them to navigate their work roles. CONCLUSIONS: The perspectives of people with IBD provided in-depth understanding of contextual factors that influence work roles. They identified personal strategies to manage health and choices about work, environmental supports that promote timely workplace accommodations, and appropriate social insurance benefits as facilitators of work retention for people with IBD. PMID- 27271488 TI - Long-term Safety and Efficacy of Low-dose Azathioprine and Allopurinol Cotherapy in Inflammatory Bowel Disease: A Large Observational Study. AB - BACKGROUND: Low-dose azathioprine with allopurinol (LDAA) has been proposed as a potent therapy in inflammatory bowel disease (IBD) with the benefit of overcoming side effects regularly associated with thiopurine monotherapy and poor responses. Concerns regarding safety remain, while a layer of complexity has been added by the trend toward treatment directed by red cell thioguanine nucleotide (TGN) profiling. We report on the clinical efficacy and safety of LDAA use in IBD undirected by metabolite profiling. METHODS: Observational study of clinical practice from a single IBD center. Patient outcomes were defined clinically based on established activity scores and corticosteroid withdrawal. Red cell TGN was monitored only for suspected nonadherence. RESULTS: Overall, 113/164 (69%) patients with Crohn's disease and 83/136 (61%) patients with ulcerative/unclassified colitis had a clinical response by the end of follow-up (median 19 months), while 85 (52%) patients with Crohn's disease and 74 (54%) patients with ulcerative/unclassified colitis were in clinical remission. Clinical response was seen in 45/57 (79%) patients with Crohn's disease and 34/53 (64%) patients with ulcerative/unclassified colitis who were thiopurine naive, had active IBD, and received LDAA as the first line immunomodulator, while in 35 (61%) and 28 (53%), respectively, remission was achieved. LDAA was stopped in 20/300 (7%) patients because of side effects, all of which resolved on drug cessation. CONCLUSIONS: This is the largest cohort supporting the favorable safety profile and high efficacy of LDAA in IBD. It presents 2 advances in therapy: prescribing LDAA for thiopurine-naive patients, and bypassing TGN monitoring in favor of clinical monitoring (blood counts, etc.), which will make it more accessible for clinics without access to TGN assays. PMID- 27271489 TI - Effect of Early Versus Late Azathioprine Therapy in Pediatric Ulcerative Colitis. AB - BACKGROUND: We aimed at describing the efficacy of azathioprine (AZA) in pediatric ulcerative colitis, comparing the outcomes of early (0-6 months) versus late (6-24 months) initiation of therapy. METHODS: Children with ulcerative colitis treated with AZA within 24 months of diagnosis were included. Corticosteroid (CS)-free remission and mucosal healing (MH), assessed by endoscopy or fecal calprotectin, at 12 months were the primary outcomes. Patients were also compared for CS-free remission and MH, need for treatment escalation or surgery, number of hospitalizations, and adverse events during a 24-month follow up. RESULTS: A total of 121 children entered the study (median age 10.5 +/- 4.0 years, 59% girls). Seventy-six (63%) started AZA between 0 and 6 months (early group) and 45 (37%) started between 6 and 24 months (late group). Seventy-five percent and 53% of patients in the early and late group, respectively, received CS at the diagnosis (P = 0.01). CS-free remission at 1 year was achieved by 30 (50%) of the early and 23 (57%) of the late patients (P = 0.54). MH occurred in 37 (37%) patients at 1 year, with no difference between the 2 groups (33% early, 42% late; P = 0.56). No difference was found for the other outcomes. CONCLUSIONS: Introduction of AZA within 6 months of diagnosis seems not more effective than later treatment to achieve CS-free remission in pediatric ulcerative colitis. MH does not depend on the timing of AZA initiation; however, because of the incomplete comparability of the 2 groups at the diagnosis and the use of fecal calprotectin as a surrogate marker of MH, our results should be further confirmed by prospective studies. PMID- 27271490 TI - Histamine Receptor 2 is Required to Suppress Innate Immune Responses to Bacterial Ligands in Patients with Inflammatory Bowel Disease. AB - BACKGROUND: Histamine is a key immunoregulatory mediator in immediate-type hypersensitivity reactions and chronic inflammatory responses, in particular histamine suppresses proinflammatory responses to bacterial ligands, through histamine receptor 2 (H2R). The aim of this study was to investigate the effects of histamine and H2R on bacteria-induced inflammatory responses in patients with IBD. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from patients with Crohn's disease, patients with ulcerative colitis, and healthy controls. PBMC histamine receptor expression was evaluated by flow cytometry. Cytokine secretion following Toll-like receptor (TLR)-2, TLR-4, TLR-5, or TLR-9 stimulation in the presence or absence of histamine or famotidine (H2R antagonist) was quantified. Biopsy histamine receptor gene expression was evaluated using reverse transcription-polymerase chain reaction. The in vivo role of H2R was evaluated in the T-cell transfer murine colitis model. RESULTS: The percentage of circulating H2R monocytes was significantly reduced in patients with IBD. Histamine effectively suppressed TLR-induced cytokine secretion from healthy volunteer PBMCs but not for PBMCs from patients with IBD. Famotidine reversed this suppressive effect. H1R, H2R, and H4R gene expression was increased in inflamed gastrointestinal mucosa compared with noninflamed mucosa from the same patient and expression levels correlated with proinflammatory cytokine gene expression. Mice receiving lymphocytes from H2R donors, or treated with famotidine, displayed more severe weight loss, higher disease scores and increased numbers of mucosal IFN-gamma and IL-17 T cells. CONCLUSION: Patients with IBD display dysregulated expression of histamine receptors, with diminished anti-inflammatory effects associated with H2R signaling. Deliberate manipulation of H2R signaling may suppress excessive TLR responses to bacteria within the gut. PMID- 27271491 TI - Mucosa-Associated Ileal Microbiota in New-Onset Pediatric Crohn's Disease. AB - BACKGROUND: The composition of the intestinal microbiome seems relevant to the pathogenesis of Crohn's disease (CD), with differences in both diversity and composition of the gut microbiota in patients with CD compared with healthy individuals. However, there are still conflicting reports on the importance of various bacterial taxa in the pathogenesis of CD. The aim of this study was to characterize the composition of mucosa-associated intestinal microbiota in newly diagnosed pediatric patients with CD. METHODS: Mucosa-associated bacteria were identified from ileal biopsy specimens obtained at colonoscopy of 10 patients with either ileal or ileocolonic new-onset CD and 15 controls without mucosal inflammation. Microbial composition was performed by profiling the 16S rDNA V6 region using Illumina sequencing. Samples were analyzed for differences in alpha/beta diversity and also for differentially abundant taxa. RESULTS: Alpha diversity did not differ between the controls and CD cases or between CD subjects with localized ileal disease compared with those with more extensive disease. Controls also did not clearly separate from patients with CD by principal coordinate analyses; however, 117 operational taxonomic units were found to be differentially abundant between the two groups. In particular, numerous operational taxonomic units associated with Faecalibacterium prausnitzii species were increased in children with CD. CONCLUSIONS: These findings contribute to emerging evidence regarding dysbiosis in pediatric CD, and provide additional evidence challenging the protective role of F. prausnitzii in CD. PMID- 27271492 TI - Crohn's Disease with Orofacial Granulomatosis Is a Distinct Disease Subtype, or Is It? PMID- 27271493 TI - Rectal Therapy in Ulcerative Colitis: Science and Sensitivity. PMID- 27271494 TI - What Proportion of Patients With Inflammatory Bowel Disease Want to Stop Infliximab Therapy? PMID- 27271495 TI - Preventing Overheating: Tight Control of Gut Innate Immunity in Health and Disease. AB - Innate immune responses are key to maintain adequate host-microbial interactions. However, those signals are needed to efficiently trigger rapid and targeted antimicrobial responses in case of pathogen encounter. Several molecules have evolved to regulate intensity and coordinate signaling to avoid detrimental consequences to the host. Regulation can occur at the cell surface, within the cytoplasm, and at the transcriptional level. Innate immune regulation seems to be equally important than stimulation, as disruption of immunoregulatory molecules modulates the risk for several diseases. This is the case for colitis and inflammatory bowel disease but also colorectal cancer and intestinal infections. In this review, we recapitulate the molecular mechanisms underlying regulation of innate immune signals and mention their implications in several disease states including inflammatory bowel disease. PMID- 27271496 TI - Different Cutoff Levels of Fecal Calprotectin to Predict Clinical Relapse in Ulcerative Colitis. PMID- 27271497 TI - Luminal Extracellular Vesicles (EVs) in Inflammatory Bowel Disease (IBD) Exhibit Proinflammatory Effects on Epithelial Cells and Macrophages. AB - BACKGROUND: Extracellular vesicles (EVs) are membrane-enclosed particles released by cells as a means of intercellular communication. They are potential novel biomarkers, as they are readily isolated from body fluids, and their composition reflects disease pathways. Whether these particles are released from sites of intestinal inflammation in inflammatory bowel disease (IBD) has not previously been determined. METHODS: EVs were isolated by ultracentrifugation of colonic luminal fluid aspirates and characterized according to surface proteins, and constituent mRNA and proteins. The effects of EVs on colonic epithelial cells and macrophages in culture were assessed at the transcriptional, translational, and functional levels. RESULTS: Intestinal luminal aspirates contained abundant EVs, at a mean concentration of 4.3 * 10 particles/mL and with a mean diameter of 146 nm. EVs from patients with IBD with a high endoscopic score (>=1) contained significantly higher mRNA and protein levels of interleukin 6 (IL-6), IL-8, IL 10, and tumor necrosis factor alpha than EVs from healthy controls. EVs were absorbed by cultured colonic epithelial cells, leading to an increased translation of IL-8 protein by recipient cells when treated with EVs from patients with IBD. EVs and EV-treated epithelial cells induced migration of a significantly greater number of macrophages than epithelial cells alone. CONCLUSIONS: EVs shed from sites of intestinal inflammation in patients with IBD have a distinct mRNA and protein profile from those of healthy individuals. These EVs have proinflammatory effects on the colonic epithelium, in vitro. Their stability in luminal samples and their mRNA and protein content identify them as a potential fecal biomarker that reflects mucosal inflammatory pathways. PMID- 27271498 TI - Reply. PMID- 27271500 TI - Randomized clinical trial: the use of SpeechEasy(r) in stuttering treatment. AB - BACKGROUND: Numerous studies have demonstrated the benefit of devices delivering altered auditory feedback (AAF) as a therapeutic alternative for those who stutter. AIMS: The effectiveness of a device delivering AAF (SpeechEasy(r)) was compared with behavioural techniques in the treatment of stuttering in a randomized clinical trial. METHODS & PROCEDURES: Two groups of adults who stutter participated: group 1 consisted of 10 men and one woman aged 21-42 years (mean = 30.0). Group 2 consisted of six men and one woman aged 20-50 years (mean = 35.6). Participants in group 1 were fit with a SpeechEasy(r) device and were not given any additional training (i.e., supplementary fluency enhancing techniques). Participants used the device daily for 6 months. Participants in group 2 received treatment in the form of a 12-week fluency promotion protocol with techniques based on both fluency shaping and stuttering modification. OUTCOMES & RESULTS: There were no statistically significant differences (p > .05) between groups in participants' stuttered syllables following treatment. That is, both therapeutic protocols achieved approximately 40% reduction in number of stuttered syllables from baseline measures, with no significant relapse after 3 or 6 months post treatment. CONCLUSIONS & IMPLICATIONS: The results suggest that the SpeechEasy(r) device can be a viable option for the treatment of stuttering. PMID- 27271499 TI - Postmortem evidence of cerebral inflammation in schizophrenia: a systematic review. AB - Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia patients. The objective of this study was to conduct a systematic search of the literature on neuroinflammation in postmortem brains of schizophrenia patients indexed in MEDLINE, Embase and PsycINFO. Databases were searched up until 20th March 2016 for articles published on postmortem brains in schizophrenia evaluating microglia, astrocytes, glia, cytokines, the arachidonic cascade, substance P and other markers of neuroinflammation. Two independent reviewers extracted the data. Out of 5385 articles yielded by the search, 119 articles were identified that measured neuroinflammatory markers in schizophrenic postmortem brains. Glial fibrillary acidic protein expression was elevated, lower or unchanged in 6, 6 and 21 studies, respectively, and similar results were obtained for glial cell densities. On the other hand, microglial markers were increased, lower or unchanged in schizophrenia in 11, 3 and 8 studies, respectively. Results were variable across all other markers, but SERPINA3 and IFITM were consistently increased in 4 and 5 studies, respectively. Despite the variability, some studies evaluating neuroinflammation in postmortem brains in schizophrenia suggest an increase in microglial activity and other markers such as SERPINA3 and IFITM. Variability across studies is partially explained by multiple factors including brain region evaluated, source of the brain, diagnosis, age at time of death, age of onset and the presence of suicide victims in the cohort. PMID- 27271503 TI - A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder. AB - BACKGROUND: The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear. METHODS: We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history. RESULTS: The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone. CONCLUSIONS: Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM 'connectivity'. PMID- 27271504 TI - Age- and Parkinson's disease-related evaluation of gait by General Tau Theory. AB - The degeneration of postural control in the elderly and patients with Parkinson's disease (PD) can be debilitating and may lead to increased fall risk. This study evaluated the changes in postural control during gait affected by PD and aging using a new method based on the General Tau Theory. Fifteen patients with PD, 11 healthy old adults (HOs), and 15 healthy young adults (HYs) were recruited. Foot trajectories of each participant were monitored during walking by a three-camera Optotrak Certus((r)) motion capture system. The anteroposterior direction of foot movement during stepping was analyzed by tau-G and tau-J guidance strategies. Two linear regression analyses suggested that the tau of the step-gap was strongly coupled onto the tau-J guidance during walking. The regression slope K could estimate the coupling ratio in the tau-coupling equation which reflects the performance of postural control during gait. The mean K value for the PD group, which was highest among the three groups, was approximately 0.5. Therefore, participants in the PD group walked with the poorest postural control and exhibited a relatively hard contact with the endpoint during stepping when compared with those in the HO and HY groups. The HY and HO groups obtained mean K values significantly lower than 0.5, which indicated that the gait was well controlled and ended at low speed with low deceleration. However, the HO group showed a decreased tendency for postural control, in which the mean K value was significantly higher than that of the HY group. The K value was moderately positively correlated with the double support time and negatively correlated with the stride length and walking speed. The tau-J coupling ratio can provide additional insight into gait disturbances and may serve as a reliable, objective, and quantitative tool to evaluate dynamic postural control during walking. PMID- 27271502 TI - Anti-citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review. AB - Anti-citrullinated peptide antibodies (ACPAs) play an important pathogenic role both at the onset and during the disease course. These antibodies precede the clinical appearance of rheumatoid arthritis (RA) and are associated with a less favorable prognosis, both clinically and radiologically. The objective of this work was to conduct a comprehensive review of studies published through September 2015 of ACPAs' role as a predictor of the therapeutic response to the biological agents in RA patients. The review also includes summary of the biology and detection of ACPAs as well as ACPAs in relation to joint disease and CV disease and the possible role of seroconversion. The reviews of studies examining TNF inhibitors and tocilizumab yielded negative results. In the case of rituximab, the data indicated a greater probability of clinical benefit in ACPA(+) patients versus ACPA(-) patients, as has been previously described for rheumatoid factor. Nonetheless, the effect is discreet and heterogeneous. Another drug that may have greater effectiveness in ACPA(+) patients is abatacept. Some studies have suggested that the drug is more efficient in ACPA(+) patients and that those patients show greater drug retention. In a subanalysis of the AMPLE trial, patients with very high ACPA titers who were treated with abatacept had a statistically significant response compared to patients with lower titers. In summary, the available studies suggest that the presence of or high titers of ACPA may predict a better response to rituximab and/or abatacept. Evidence regarding TNFi and tocilizumab is lacking. However, there is a lack of studies with appropriate designs to demonstrate that some drugs are superior to others for ACPA(+) patients. PMID- 27271506 TI - Screening for Pancreatic Adenocarcinoma Using Signals From Web Search Logs: Feasibility Study and Results. AB - INTRODUCTION: People's online activities can yield clues about their emerging health conditions. We performed an intensive study to explore the feasibility of using anonymized Web query logs to screen for the emergence of pancreatic adenocarcinoma. The methods used statistical analyses of large-scale anonymized search logs considering the symptom queries from millions of people, with the potential application of warning individual searchers about the value of seeking attention from health care professionals. METHODS: We identified searchers in logs of online search activity who issued special queries that are suggestive of a recent diagnosis of pancreatic adenocarcinoma. We then went back many months before these landmark queries were made, to examine patterns of symptoms, which were expressed as searches about concerning symptoms. We built statistical classifiers that predicted the future appearance of the landmark queries based on patterns of signals seen in search logs. RESULTS: We found that signals about patterns of queries in search logs can predict the future appearance of queries that are highly suggestive of a diagnosis of pancreatic adenocarcinoma. We showed specifically that we can identify 5% to 15% of cases, while preserving extremely low false-positive rates (0.00001 to 0.0001). CONCLUSION: Signals in search logs show the possibilities of predicting a forthcoming diagnosis of pancreatic adenocarcinoma from combinations of subtle temporal signals revealed in the queries of searchers. PMID- 27271505 TI - Financial incentives enhance adaptation to a sensorimotor transformation. AB - Adaptation to sensorimotor transformations has received much attention in recent years. However, the role of motivation and its relation to the implicit and explicit processes underlying adaptation has been neglected thus far. Here, we examine the influence of extrinsic motivation on adaptation to a visuomotor rotation by way of providing financial incentives for accurate movements. Participants in the experimental group "bonus" received a defined amount of money for high end-point accuracy in a visuomotor rotation task; participants in the control group "no bonus" did not receive a financial incentive. Results showed better overall adaptation to the visuomotor transformation in participants who were extrinsically motivated. However, there was no beneficial effect of financial incentives on the implicit component, as assessed by the after-effects, and on separately assessed explicit knowledge. These findings suggest that the positive influence of financial incentives on adaptation is due to a component which cannot be measured by after-effects or by our test of explicit knowledge. A likely candidate is model-free learning based on reward-prediction errors, which could be enhanced by the financial bonuses. PMID- 27271507 TI - Variations in Oncologist Recommendations for Chemotherapy for Stage IV Lung Cancer: What Is the Role of Performance Status? AB - PURPOSE: Chemotherapy prolongs survival in patients with advanced non-small-cell lung cancer. However, few studies have included patients with poor performance status. This study examined rates of oncologists' recommendations for chemotherapy by patient performance status and symptoms and how physician characteristics influence chemotherapy recommendations. METHODS: We surveyed medical oncologists involved in the care of a population-based cohort of patients with lung cancer from the CanCORS (Cancer Care Outcomes Research and Surveillance) study. Physicians were queried about their likelihood to recommend chemotherapy to patients with stage IV lung cancer with varying performance status (Eastern Cooperative Oncology Group performance status 0 [good] v 3 [poor]) and presence or absence of tumor-related pain. Repeated measures logistic regression was used to estimate the independent associations of patients' performance status and symptoms and physicians' demographic and practice characteristics with chemotherapy recommendations. RESULTS: Nearly all physicians (adjusted rate, 97% to 99%) recommended chemotherapy for patients with good performance status, and approximately half (adjusted rate, 38% to 53%) recommended chemotherapy for patients with poor performance status (P < .001). Compared with patient factors, physician and practice characteristics were less strongly associated with chemotherapy recommendations in adjusted analyses. CONCLUSION: Strong consensus among oncologists exists for chemotherapy in patients with advanced non-small-cell lung cancer and good performance status. However, the relatively high rate of chemotherapy recommendations for patients with poor performance status despite the unfavorable risk-benefit profile highlights the need for ongoing work to define high-value care in oncology and to implement and evaluate strategies to align incentives for such care. PMID- 27271509 TI - Cross-sectional imaging of complicated urinary infections affecting the lower tract and male genital organs. AB - Complicated urinary tract infections (C-UTIs) are those associated with structural or functional genitourinary abnormalities or with conditions that impair the host defence mechanisms, leading to an increased risk of acquiring infection or failing therapy. C-UTIs occur in patients with risk factors such as neurogenic dysfunction, bladder outlet obstruction, obstructive uropathy, bladder catheterisation, urologic instrumentation or indwelling stent, urinary tract post surgical modifications, chemotherapy- or radiation-induced damage, renal impairment, diabetes and immunodeficiency.Multidetector CT and MRI allow comprehensive investigation of C-UTIs and systemic infection from an unknown source. Based upon personal experience at a tertiary care hospital focused on the treatment of infectious illnesses, this pictorial essay reviews with examples the clinical features and cross-sectional imaging findings of C-UTIs affecting the lower urinary tract and male genital organs. The disorders presented include acute infectious cystitis, bladder mural abscesses, infections of the prostate and seminal vesicles, acute urethritis and related perineal abscesses, funiculitis, epididymo-orchitis and scrotal abscesses. Emphasis is placed on the possible differential diagnoses of lower C-UTIs.The aim is to provide radiologists greater familiarity with these potentially severe disorders which frequently require intensive in-hospital antibiotic therapy, percutaneous drainage or surgery. Teaching Points * Complicated urinary tract infections occur in patients with structural or functional risk factors.* CT and MRI comprehensively investigate complicated urinary infections and sepsis from unknown sources.* Infections of the urinary bladder, prostate, seminal vesicles, urethra and scrotum are presented.* Emphasis is placed on differential diagnoses of complicated lower urogenital infections.* Unsuspected urinary infections may be detected on CT performed for other clinical reasons. PMID- 27271508 TI - Thyroid computed tomography imaging: pictorial review of variable pathologies. AB - Focal and diffuse thyroid abnormalities are commonly encountered during the interpretation of computed tomography (CT) exams performed for various clinical purposes. These findings can often lead to a diagnostic dilemma, as the CT reflects the nonspecific appearances. Ultrasound (US) examination has a superior spatial resolution and is considered the modality of choice for thyroid evaluation. Nevertheless, CT detects incidental thyroid nodules (ITNs) and plays an important role in the evaluation of thyroid cancer. In this pictorial review, we cover a wide spectrum of common and uncommon, incidental and non-incidental thyroid findings from CT scans. We also discuss the most common incidental thyroid findings, best practices for their evaluation, and recommendations for their management. In addition, we explore the role of imaging in the assessment of thyroid carcinoma (before and after treatment) and preoperative thyroid goiter, as well as localization of ectopic and congenital thyroid tissue. TEACHING POINTS: * Thyroid disorders tend to have non-specific CT appearances. * ITNs are common on neck CT. * ITN management depends on nodule size, age, health status, lymphadenopathy, and invasion. * CT is used in assessment of cancer extension, mass effect, invasion, and recurrence. * CT plays a role in preoperative planning in patients with symptomatic goiter. PMID- 27271510 TI - The clothes maketh the sign. AB - Pattern recognition is a key tool that enables radiologists to evoke certain diagnoses based on a radiologic appearance. In Shakespeare's Hamlet, Polonius tells his son Laertes to dress well because "apparel oft proclaims the man"; this phrase is now expressed in modern parlance as "the clothes maketh the man". Similarly in radiology, appearances are everything, and in the case of radiologic signs, occasionally "the clothes maketh the sign". The radiologic signs described in this pictorial review resemble items of clothing, fabric types, headwear, or accessories and are found in the musculoskeletal, pulmonary, gastrointestinal, and genitourinary systems. These "clothing signs" serve as a useful visual trigger to help radiologists to identify particular disease entities. TEACHING POINTS: * Pattern recognition enables radiologists to evoke a diagnosis based on radiologic appearance. * The radiologic signs described in this review resemble clothing, fabric, or accessories. * These "clothing signs" serve as visual triggers that evoke particular disease entities. PMID- 27271511 TI - Lipopolysaccharide-Activated Leukocytes Enhance Thymic Stromal Lymphopoietin Production in a Mouse Air-Pouch-Type Inflammation Model. AB - Thymic stromal lymphopoietin (TSLP) is a key cytokine that exacerbates allergic and fibrotic reactions. Several microbes and virus components have been shown to induce TSLP production, mainly in epithelial cells. TLR4 activators, such as lipopolysaccharide (LPS), induce TSLP production in vivo, although the underlying mechanisms remain unclear. In this study, we investigated the contribution of LPS activated leukocytes to the production of TSLP in a mouse air-pouch-type inflammation model. LPS induced the production of TSLP in this model but not in the mouse keratinocyte cell line PAM212. Transfer of the infiltrated leukocytes collected from an LPS-injected air pouch to the air pouch of another mouse enhanced TSLP production. Further, the LPS-activated leukocytes produced tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta); a deficiency in these cytokines attenuated the LPS-induced production of TSLP. TSLP production was induced by TNF-alpha and enhanced by IL-1beta and LPS in the PAM212 cells. These results demonstrated that TNF-alpha and IL-1beta, which are partly produced by LPS-activated leukocytes, contribute to TSLP production via TLR4 activation in vivo. PMID- 27271512 TI - Anti-inflammatory Evaluation and Toxicological Analysis of Campomanesia xanthocarpa Berg. AB - Campomanesia xanthocarpa (Myrtaceae) is used in Brazilian traditional medicine against fever, diabetes, hypercholesteremic, obesity, and urinary diseases. In the present study, the compounds 2',6'-dihydroxy-3'-methyl-4'-metoxychalcone and 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone were identified for the first time in leaves of the C. xanthocarpa. These compounds and the hydroethanolic extract (HECX) significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. No toxicity was detected by HECX in an acute toxicity test. PMID- 27271513 TI - Enhanced p62 Is Responsible for Mitochondrial Pathway-Dependent Apoptosis and Interleukin-1beta Production at the Early Phase by Monosodium Urate Crystals in Murine Macrophage. AB - The aim of this study was to clarify the role of p62-dependent mitochondrial apoptosis in the initiation of monosodium urate (MSU) crystal-induced inflammation in macrophages. The induction of mitochondrial apoptosis in RAW 264.7 murine macrophages by MSU crystals was measured using western blotting and quantitative real-time polymerase chain reaction for Bax, caspase-3, caspase-9, or PARP1, and by flow cytometric analysis. Immunoprecipitation and western blotting was applied to detect ubiquitination of p62, TRAF6, and caspase-9. Mitochondrial apoptosis, reactive oxygen species (ROS) generation, and cell proliferation were assessed in cells transfected with p62 small interfering RNA (siRNA). Treatment of RAW 264.7 cells with MSU crystals induced activation of Bax, caspase-3, caspase-9, and PARP1 at the early phase, in addition to enhancing IL-1beta expression, but these findings were attenuated at the late phase. MSU crystals induced ubiquitination of p62, followed by ubiquitination of TRAF6 and caspase-9, which were significantly reversed by ascorbic acid. RAW 264.7 cells transfected with p62 siRNA showed attenuated expression of Bax, caspase-3, caspase-9, and PARP1, decreased ROS and IL-1beta production, and increased cell proliferation, compared to controls. The antioxidant ascorbic acid inhibited p62, caspase-9, and IL-1beta expression increased by MSU crystals. p62 may be a crucial mediator for the mitochondrial apoptosis pathway in MSU crystal-induced inflammation, which is linked to the acute inflammatory response during the early phase of gout. PMID- 27271514 TI - [Neurological podcasting : A project by students for students]. AB - BACKGROUND: Podcasts are a very popular learning material among medical students. Currently only a few neurological podcasts exist, which do not include relevant neurological diseases or neuroanatomical contents. OBJECTIVE: The primary objective of this project was to help medical students understand neurological topics and to integrate them into the educational program. MATERIAL AND METHODS: The project started in 2014. The podcasts were written and produced by medical students. So far ten podcasts about neuroanatomy and clinical neurology have been created. The podcasts were published in summer 2015 at the University of Witten Herdecke followed by an internal evaluation. In addition to questions about the listening experience and intelligibility, the students were asked to give an individual evaluation of the different topics and to express their opinion in a free text field. RESULTS: A total of 100 medical students participated. They listened to the podcasts in particular to prepare themselves for medical examinations (47.4 %) and because of a special interest in neurology (26.3 %). The different podcasts were mainly evaluated as "good" or "very good". Of the students 76.8 % wanted to listen to the podcasts again and 93 % planned to recommend the podcasts to friends. Only the length of some of the podcasts as well as technical faults were criticized and should be improved. CONCLUSION: The neurological podcasts of the University of Witten-Herdecke are a very successful and well-received project. The results of the survey will help to improve the next podcasts and integrate new topics. More than 15 new podcasts are being edited at the moment. The release date for the new podcasts will be in spring 2016. PMID- 27271515 TI - [Perampanel as a therapy option in patients with epilepsy]. AB - BACKGROUND: This article describes a monocentric retrospective analysis of clinical experience with the latest antiepileptic drug perampanel with non competitive modulation of postsynaptic AMPA receptors. MATERIAL AND METHODS: Evaluation of electronic medical charts of patients newly treated with perampanel between 2012 and 2014 at the epilepsy center of the University Hospital Freiburg regarding effectiveness and tolerability. RESULTS: A total of 85 patients (45 male, mean age 37.4 years, range 14-80 years) with therapy resistance to an average of 6 antiepileptic medications were newly treated with add-on perampanel. Of the patients 35 % experienced a relevant reduction in seizures. The most commonly reported side effects were tiredness (32.5 %), dizziness (24.5 %) and irritability (10.5 %). The dosages resulting in a significant reduction in seizures which varied between patients from 4 to 12 mg/day. Even multidrug resistant patients who had not benefited from vagus nerve and deep brain stimulation, profited from add-on treatment with perampanel. CONCLUSION: In this cohort, even epilepsy patients who did not respond to multiple previous antiepileptic treatment profited from add-on therapy with the new mode of action of perampanel. PMID- 27271516 TI - [Guideline-adherent inpatient psychiatric psychotherapeutic treatment of borderline personality disorder : Normative definition of personnel requirements]. AB - BACKGROUND: Borderline personality disorders (BPD) are severe mental diseases which place high pressure on the psychiatric healthcare system. Nowadays, well tested, disorder-specific treatment concepts are available also for inpatient treatment in Germany. These show very good and long-term improvements in the psychopathology as well as posttreatment social participation; however, prerequisites for the implementation of these evidence-based inpatient psychotherapy programs are well-trained treatment teams and appropriate financing of resource expenditure. OBJECTIVE: The aim was to formulate a definition of normative needs for treatment duration and intensity for a guideline-conform, empirically proven and effective inpatient treatment of borderline personality disorder as well as the derived personnel requirements in comparison to the currently available resources within the framework of the Psychiatry Personnel Act (Psych-PV). MATERIAL AND METHODS: The resource requirements were established based on evaluated hospital ward models, the recommendations of the S2 guidelines and the criteria of specialist societies and compared with the personnel stipulations according to the Psych-PV. RESULTS: The results for a normatively established treatment program showed a pronounced deficit in the financing of the evaluated resource requirements, even when the stipulations laid down in the Psych-PV were implemented to 100 %. DISCUSSION: Disorder-specific inpatient treatment programs for borderline personality disorder have been scientifically proven to be highly effective; however, resource analyses show that the personnel requirements necessary for effective implementation of these programs are much higher than those allocated by the funding according to the Pysch-PV. The current underfunding leads to inadequate treatment outcomes with high readmission rates and as a result high direct and indirect costs of illness. PMID- 27271518 TI - Erratum. PMID- 27271517 TI - [Implementation of the recommendations for psychotherapy after psychiatric inpatient treatment : Results of the PAKT study Part II]. AB - BACKGROUND: Waiting periods for inpatient or outpatient psychotherapeutic treatment are generally considerable. For patients treated in a psychiatric day clinic or hospital, implementation of a recommended subsequent psychotherapeutic treatment might be difficult. OBJECTIVES: In part II of the psychotherapy after hospital or day clinic (PAKT) study, we examined how the recommendation for psychotherapy can be implemented after psychiatric treatment. MATERIALS AND METHODS: Three months after discharge from one of four psychiatric hospitals in southern Germany, we interviewed 306 patients who received a recommendation for psychotherapeutic treatment after their hospital stays if the recommendation was implemented successfully. RESULTS: Only about 12 % of the patients in the follow up group were unable to implement the general recommendation for psychotherapy after psychiatric stay despite motivation for psychotherapeutic treatment. In the case of recommendation for outpatient psychotherapy, 20 % were unsuccessful. Predictors for successful implementation were education and employment, whereas variables like age, gender, diagnosis, or severity of disorder did not play a significant role. CONCLUSIONS: The relatively small percentage of unimplemented psychotherapeutic treatment is surprising at a first glance. However, the proportion recommended for psychotherapy after psychiatric stay was less than 10 %, as shown in the first part of the study (see PAKT Study Part I, doi:s00115-016 0107-z). PMID- 27271519 TI - Site-specific integration of CAR gene into Jurkat T cells with a linear close ended AAV-based DNA vector for CAR-T engineering. AB - OBJECTIVES: To develop a site-specific integration strategy for CAR-T engineering by using a non-viral vector dependent on adeno-associated viral (AAV) genome, which tends to be integrated into AAVS1 site with the help of its Rep proteins. RESULTS: AAV-dependent vectors were produced in Sf9 cells. Structural analyses revealed the vector as covalently close-ended, linear duplex molecules, which was termed "CELiD" DNA. A plasmid CMV-Rep was constructed to express the integrases Rep78 and Rep68. Jurkat cells were co-electroporated with "CELiD" DNA and plasmid CMV-Rep in order to specifically integrate CAR gene into AAVS1 site. We examined 71 stably transfected Jurkat clones by nested PCR, sequencing and southern blotting, of which 30 clones bore CAR gene within AAVS1 site. The site-specific integration efficiency was nearly 42.2 %. CONCLUSIONS: The AAV-dependent vector preferentially integrated CAR into AAVS1 site, which could be further used in human T cell modification and enhance the security of CAR-T therapy. PMID- 27271520 TI - Extending the linker region increases the activity of the Bacillus subtilis cellulase CelI15. AB - OBJECTIVES: To investigate the effect of the linker region (LR) on the enzymatic activity, stability, and flexibility of Bacillus subtilis cellulase CelI15, six mutants were constructed that contained increasing numbers of the LR. RESULTS: The CelI15 mutant with three copies of the LR (approx. 57 amino acids) showed the highest activity, which was almost 20 % greater than that of wild type CelI15. The stability of the mutant enzymes increased as the copy number of the LR decreased. However, the substrate affinity of the mutant enzymes increased as the LR copy number increased, and the mutant with four copies of the LR exhibited the highest substrate affinity. Additionally, the flexibility of the CelI15 mutants increased as the LR copy number increased from zero to four copies, although it decreased sharply for the mutant with five copies of the LR. CONCLUSION: The activity of CelI15 was increased by increasing the LR copy number, which could be a potential way to improve its enzymatic properties. PMID- 27271521 TI - Versatility of chitosan/BmNPV bacmid DNA nanocomplex as transfection reagent of recombinant protein expression in silkworm larvae. AB - OBJECTIVE: To examine the feasibility of chitosan as an alternative transfection reagent candidate for protein expression in Bm5 cells and silkworm larvae using recombinant BmNPV bacmid DNA. RESULT: Chitosan 100 and recombinant Bombyx mori nucleopolyhedrovirus (BmNPV) bacmid DNA, in amino group/phosphate group (N/P) ratios of 0.1-10, were used for formation of chitosan/DNA nanocomplexes. The chitosan/BmNPV bacmid DNA nanocomplexes showed higher specific activity of GFPuv beta1,3-N-acetylglucosaminyltransferase 2 (beta3GnT2) fusion protein (GGT2) expressed in silkworm larvae than DMRIE-C, a conventional silkworm transfection reagent. In particular, the composition of chitosan and BmNPV bacmid DNA nanocomplexes formed by an N/P ratio of 8 or 10, respectively, showed the highest specific activity of beta3GnT2 in the silkworm larvae hemolymph. In addition, three different proteins were expressed in silkworm larvae to the same extent using chitosan as that using DMRIE-C. CONCLUSION: This is the first finding that chitosan/BmNPV bacmid DNA nanocomplexes can rival the performance of commercially available transfection reagents for the expression of recombinant proteins in Bm5 cells and silkworm larvae. PMID- 27271522 TI - Biodegradation of ketoprofen using a microalgal-bacterial consortium. AB - OBJECTIVE: To test the toxicity of ketoprofen (a commonly-used NSAIDs) using two microalgal strains and Artemia sp. following the isolation of bacterial and microalgal strains and testing their ability to biodegrade and tolerate ketoprofen. RESULTS: Chlorella sp. was the most resistant to ketoprofen. A defined bacterial consortium (K2) degraded 5 mM ketoprofen as a sole carbon source both in the dark or continuous illumination. Ketoprofen did not undergo photodegradation. In the dark, biodegradation was faster with a lag phase of 10 h, 41% COD removal and 82 % reduction in toxicity. The consortium degraded up to 16 mM ketoprofen. The consortium was composed of four bacterial isolates that were identified. MS/MS analysis suggested a ketoprofen biodegradation pathway that has not been previously reported. Combining Chlorella sp. and the K2 consortium, ketoprofen was degraded within 7 days under a diurnal cycle of 12 h light/12 h dark. CONCLUSION: The feasibility of using a microalgal-bacterial system to treat pharmaceutical wastewater is promising for the reduction of the process cost and providing a safer technology for pharmaceutical wastewater treatment. PMID- 27271523 TI - Neonatal Benzo[a]pyrene Exposure Induces Oxidative Stress and DNA Damage Causing Neurobehavioural Changes during the Early Adolescence Period in Rats. AB - Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) by ingestion of contaminated food and water. Prenatal exposure to benzo[a]pyrene (B[a]P) like PAHs through the placental barrier and neonatal exposure by breast milk and the environment may affect early brain development. In the present study, single intracisternal administration of B[a]P (0.2 and 2.0 ug/kg body weight) to male Wistar rat pups at postnatal day 5 (PND5) was carried out to study its specific effect on neonatal brain development and its consequences at PND30. B[a]P administration showed a significant increase in exploratory and anxiolytic-like behaviour with elevated hippocampal lipid peroxidation and protein oxidation at PND30. Further, DNA damage was estimated in vitro (Neuro2a and C6 cell lines) by the comet assay, and oxidative DNA damage of hippocampal sections was measured in vivo following exposure to B[a]P. DNA strand breaks (single and double) significantly increased due to B[a]P at PND30 in hippocampal neurons and increased the nuclear tail moment in Neuro2a cells. Hippocampal 8-oxo-2' deoxyguanosine production was significantly elevated showing expression of more TUNEL-positive cells in both doses of B[a]P. Histological studies also revealed a significant reduction in mean area and perimeter of hippocampal neurons in rats treated with B[a]P 2.0 MUg/kg, when compared to naive and control rats. B[a]P significantly increased anxiolytic-like behaviour and oxidative DNA damage in the hippocampus causing apoptosis that may lead to neurodegeneration in adolescence. The findings of the present study address the potential role of B[a]P in inducing oxidative stress-mediated neurodegeneration in the hippocampus through oxidative DNA damage in the early adolescence period of rats. PMID- 27271525 TI - Human Milk in Feeding Premature Infants: From Tradition to Bioengineering: Erratum. PMID- 27271524 TI - Coupling of attention and saccades when viewing scenes with central and peripheral degradation. AB - Degrading real-world scenes in the central or the peripheral visual field yields a characteristic pattern: Mean saccade amplitudes increase with central and decrease with peripheral degradation. Does this pattern reflect corresponding modulations of selective attention? If so, the observed saccade amplitude pattern should reflect more focused attention in the central region with peripheral degradation and an attentional bias toward the periphery with central degradation. To investigate this hypothesis, we measured the detectability of peripheral (Experiment 1) or central targets (Experiment 2) during scene viewing when low or high spatial frequencies were gaze-contingently filtered in the central or the peripheral visual field. Relative to an unfiltered control condition, peripheral filtering induced a decrease of the detection probability for peripheral but not for central targets (tunnel vision). Central filtering decreased the detectability of central but not of peripheral targets. Additional post hoc analyses are compatible with the interpretation that saccade amplitudes and direction are computed in partial independence. Our experimental results indicate that task-induced modulations of saccade amplitudes reflect attentional modulations. PMID- 27271526 TI - Three-dimensional core-shell ferromagnetic nanowires grown by focused electron beam induced deposition. AB - Functional nanostructured materials often rely on the combination of more than one material to confer the desired functionality or an enhanced performance of the device. Here we report the procedure to create nanoscale heterostructured materials in the form of core-shell nanowires by focused electron beam induced deposition (FEBID) technologies. In our case, three-dimensional (3D) nanowires (<100 nm in diameter) with metallic ferromagnetic cores of Co- and Fe-FEBID have been grown and coated with a protective Pt-FEBID shell (ranging 10-20 nm in thickness) aimed to minimize the degradation of magnetic properties caused by the surface oxidation of the core to a non-ferromagnetic material. The structure, chemistry and magnetism of nanowire cores of Co and Fe have been characterized in Pt-coated and uncoated nanostructures to demonstrate that the morphology of the shell is conserved during Pt coating, the surface oxidation is suppressed or confined to the Pt layer, and the average magnetization of the core is strengthened up to 30%. The proposed approach paves the way to the fabrication of 3D FEBID nanostructures based on the smart alternate deposition of two or more materials combining different physical properties or added functionalities. PMID- 27271527 TI - Skin disease symptoms and related risk factors among young workers in high-risk jobs. AB - BACKGROUND: Occupational skin diseases are the one of the most frequent diseases in many industrialized countries. The studies about skin disease (SD) on young workers were limited. OBJECTIVES: In this study, we aim to evaluate the prevalence of SD symptoms and related risk factors among young workers in high risk occupations. METHODS: This cross-sectional study was undertaken between 2011 and 2012 in two vocational training centres. We included 455 young workers who were working as hairdressers, jewellers, or car mechanics. Data were collected with the Nordic Occupational Skin Questionnaire, which was adapted to Turkish for young workers. RESULTS: The average age of the young workers was 17.9 +/- 1.7 years. Of the 455 young workers, 52.7% were female and 47.3% were male. During the previous 12 months, the prevalences of the total SD symptoms, hand/forearm eczema symptoms and urticaria symptoms were 49.7%, 44.4%, and 13.4%, respectively. Those who worked as car mechanics were 5.8 times more likely [odds ratio (OR) 5.81, 95%CI: 2.58-13.10) to have a dry skin type, 2.9 times more likely (OR 2.86, 95%CI: 1.72-4.75) to work for >12 h daily, 2.6 times more likely (OR 2.59, 95%CI: 1.25-5.35) to have worked for >5 years, and 3.0 times more likely (OR 3.05, 95%CI: 1.14-8.14) to have SD symptoms. CONCLUSION: The results indicate that young workers in high-risk jobs have a high frequency of skin symptoms. These results could provide a basis for occupational health professionals to plan prevention programmes for young workers. PMID- 27271528 TI - An Introduction to Programming for Bioscientists: A Python-Based Primer. AB - Computing has revolutionized the biological sciences over the past several decades, such that virtually all contemporary research in molecular biology, biochemistry, and other biosciences utilizes computer programs. The computational advances have come on many fronts, spurred by fundamental developments in hardware, software, and algorithms. These advances have influenced, and even engendered, a phenomenal array of bioscience fields, including molecular evolution and bioinformatics; genome-, proteome-, transcriptome- and metabolome wide experimental studies; structural genomics; and atomistic simulations of cellular-scale molecular assemblies as large as ribosomes and intact viruses. In short, much of post-genomic biology is increasingly becoming a form of computational biology. The ability to design and write computer programs is among the most indispensable skills that a modern researcher can cultivate. Python has become a popular programming language in the biosciences, largely because (i) its straightforward semantics and clean syntax make it a readily accessible first language; (ii) it is expressive and well-suited to object-oriented programming, as well as other modern paradigms; and (iii) the many available libraries and third-party toolkits extend the functionality of the core language into virtually every biological domain (sequence and structure analyses, phylogenomics, workflow management systems, etc.). This primer offers a basic introduction to coding, via Python, and it includes concrete examples and exercises to illustrate the language's usage and capabilities; the main text culminates with a final project in structural bioinformatics. A suite of Supplemental Chapters is also provided. Starting with basic concepts, such as that of a "variable," the Chapters methodically advance the reader to the point of writing a graphical user interface to compute the Hamming distance between two DNA sequences. PMID- 27271530 TI - OLA1 gene sequencing in patients with BRCA1/2 mutation-negative suspected hereditary breast and ovarian cancer. AB - BACKGROUND: Of individuals with suspected hereditary breast and ovarian cancer (HBOC), approximately 30-70 % do not harbor mutations in either BRCA1 or BRCA2 gene, which suggests that these individuals have other genetic or epigenetic alterations that could lead to the onset of this hereditary disease. We have recently identified OLA1 as a novel BRCA1/BARD1-interacting protein. In the present study, we aimed to elucidate whether any genetic mutations in OLA1 are detected among patients with suspected HBOC without BRCA1 or BRCA2 mutations. METHODS: Among 53 patients with suspected HBOC enrolled at Hoshi General Hospital, 23 patients without any BRCA1 or BRCA2 mutations were analyzed for OLA1 mutations. Genomic DNA was extracted from the peripheral blood samples. PCR and Sanger sequencing were performed to elucidate whether there were any mutations in any of the ten exons and flanking introns of the OLA1 gene. RESULTS: No germline sequence variation was detected in the OLA1 gene among the 23 patients enrolled in this study. CONCLUSIONS: No germline mutations were found in the OLA1 gene among the cohort of patients with suspected HBOC without BRCA1 or BRCA2 mutations. Further studies are needed to clarify whether other mutations/epigenetic alterations are involved in the pathogenesis of BRCA1 or BRCA2 mutation-negative inherited disease with breast or ovarian cancer. PMID- 27271529 TI - Racial/Ethnic Differences in Contemporaneous Use of Mental Health and Substance Use Treatment Among Individuals Experiencing Both Mental Illness and Substance Use Disorders. AB - This study examined whether the well-established racial/ethnic differences in mental health service utilization among individuals with mental illness are reflected in the treatment utilization patterns of individuals experiencing both mental illness and substance use disorders, particularly in regards to the use of contemporaneous mental health and substance abuse treatment. Using pooled data from the National Survey on Drug Use and Health (2009-2013), the patterns of mental health and substance use treatment utilization of 8748 White, Black, or Latino individuals experiencing both mental illness and substance use disorders were analyzed. Multinomial logistic regression was conducted to test the relationships among racial/ethnic groups and the receipt of contemporaneous treatment, mental health treatment alone, and substance use treatment alone as compared with no treatment utilization. Results indicated that Black and Latino respondents were less likely to receive contemporaneous treatment than Whites respondents. Also, significantly associated with outcomes were several interactions between race/ethnicity and predisposing, need and enabling factors known to be associated with service utilization. The findings suggest that an underlying mechanism of racial/ethnic differences among individuals with co occurring mental illness and substance use disorders in the treatment utilization may differ by the specific types of treatment and between Blacks and Latinos. Therefore, efforts to reduce these disparities should consider specialty in each treatment settings and heterogeneity within diverse racial/ethnic groups. PMID- 27271531 TI - Cumulative trauma and partner conflict predict post-traumatic stress disorder in postpartum African-American women. AB - AIM AND OBJECTIVE: To describe relationships between cumulative trauma, partner conflict and post-traumatic stress in African-American postpartum women. BACKGROUND: Cumulative trauma exposure estimates for women in the USA range from 51-69%. During pregnancy, most trauma research has focused on physical injury to the mother. Post-traumatic stress disorder (PTSD) is associated with trauma and more prevalent in African-American women than women of other groups. Knowledge about both the rate and impact of cumulative trauma on pregnancy may contribute to our understanding of women seeking prenatal care, and disparities in infant morbidity and mortality. DESIGN: This retrospective, correlational, cross sectional study took place on postpartum units of two Detroit hospitals. Participants were 150 African-American women aged between 18-45 who had given birth. METHODS: Mothers completed the Cumulative Trauma Scale, Conflict Tactics Scale, Clinician Administered Post-traumatic Stress Scale, Edinburgh Postnatal Depression Scale and a Demographic Data form. Descriptive statistics, correlations and multiple regressions were used for data analysis. RESULTS: All participants reported at least one traumatic event in their lifetime. Cumulative trauma and partner conflict predicted PTSD, with the trauma of a life-threatening event for a loved one reported by 60% of the sample. Nearly, one-fourth of the women screened were at risk for PTSD. Increased cumulative trauma, increased partner conflict and lower level of education were related to higher rates of PTSD symptoms. CONCLUSION: Both cumulative trauma and partner conflict in the past year predict PTSD. Reasoning was used most often for partner conflict resolution. RELEVANCE TO CLINICAL PRACTICE: The results of this study offer additional knowledge regarding relationships between cumulative trauma, partner conflict and PTSD in African-American women. Healthcare providers need to be sensitive to patient life-threatening events, personal failures, abuse and other types of trauma. Current evidence supports the need to assess for post-traumatic stress symptoms during pregnancy. PMID- 27271532 TI - Differences in cardiovascular manifestations between ankylosing spondylitis patients with and without kyphosis. AB - The objective of this study is to evaluate the differences in cardiovascular manifestations between ankylosing spondylitis (AS) patients with and without kyphosis. A retrospective review of consecutive AS patients treated at our hospital between June 2013 and June 2015 was performed. There were 122 patients who met all of the inclusion and exclusion criteria. Among these patients, there were 57 (ASK group) patients with global kyphosis (GK) > 40 degrees and 65 (AS group) patients with GK < 40 degrees . General information, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), electrocardiography, and echocardiography were record. ESR and CRP levels in the ASK group were significantly higher than the AS group (P < 0.05). Fifteen patients in ASK group but 3 patients in AS group suffered from a left ventricular high voltage (P < 0.05). Heart rate in ASK group was 83.91 +/- 13.68 beats/min, and it was 73.88 +/ 13.04 beats/min in AS group (P < 0.05). The E/A ratio was 1.13 +/- 0.38 in ASK group and 1.32 +/- 0.49 in AS group (P < 0.05). The mitral E-wave deceleration time and isovolumetric relaxation time were, respectively, 236.25 +/- 34.26 ms and 101.86 +/- 17.57 ms in ASK group, which were shorter in AS group (P < 0.05). This study showed that AS patients with kyphosis had a statistically increased incidence of cardiovascular complications including a more rapid heart rate, left ventricular high voltage, and left ventricular diastolic dysfunction. PMID- 27271533 TI - Proposition of a Classification of Adult Patients with Hemiparesis in Chronic Phase. AB - BACKGROUND: Patients who have developed hemiparesis as a result of a central nervous system lesion, often experience reduced walking capacity and worse gait quality. Although clinically, similar gait patterns have been observed, presently, no clinically driven classification has been validated to group these patients' gait abnormalities at the level of the hip, knee and ankle joints. This study has thus intended to put forward a new gait classification for adult patients with hemiparesis in chronic phase, and to validate its discriminatory capacity. METHODS AND FINDINGS: Twenty-six patients with hemiparesis were included in this observational study. Following a clinical examination, a clinical gait analysis, complemented by a video analysis, was performed whereby participants were requested to walk spontaneously on a 10m walkway. A patient's classification was established from clinical examination data and video analysis. This classification was made up of three groups, including two sub-groups, defined with key abnormalities observed whilst walking. Statistical analysis was achieved on the basis of 25 parameters resulting from the clinical gait analysis in order to assess the discriminatory characteristic of the classification as displayed by the walking speed and kinematic parameters. Results revealed that the parameters related to the discriminant criteria of the proposed classification were all significantly different between groups and subgroups. More generally, nearly two thirds of the 25 parameters showed significant differences (p<0.05) between the groups and sub-groups. However, prior to being fully validated, this classification must still be tested on a larger number of patients, and the repeatability of inter-operator measures must be assessed. CONCLUSIONS: This classification enables patients to be grouped on the basis of key abnormalities observed whilst walking and has the advantage of being able to be used in clinical routines without necessitating complex apparatus. In the midterm, this classification may allow a decision-tree of therapies to be developed on the basis of the group in which the patient has been categorised. PMID- 27271535 TI - Informal processing of electronic waste at Agbogbloshie, Ghana: workers' knowledge about associated health hazards and alternative livelihoods. AB - AIMS: This study was conducted to investigate the electronic waste workers' knowledge about the potential health hazards associated with their work as well as the livelihood alternatives that they would prefer if they were given the opportunity. METHODS: A qualitative cross-sectional study was conducted to gather empirical information on e-waste workers' knowledge about the potential hazards associated with their work and the livelihood alternatives to e-waste recycling with a sample consisting of twenty all-male electronic waste workers at the Agbogbloshie scrap metal yard in Accra, Ghana. RESULTS: Electronic waste workers at Agbogbloshie were found to be exposed to a variety of injuries and illnesses. The workers' knowledge of the association between their health status and their work was generally poor. Apart from the physical injuries, they did not believe their work played any negative role in their health conditions. They preferred occupations such as farming or professional driving located in the northern region of Ghana to be closer to their families. CONCLUSIONS: The study concludes that the low knowledge level of the workers on the hazards that are associated with their work has implications for them accepting technologies to protect them and the natural environment from contamination. It is therefore imperative for any intervention to consider the current low level of knowledge and actively educate the workers to raise their awareness level, taking into account the provision of opportunities for workers to acquire applicable skills for future employment in other fields. PMID- 27271534 TI - Metagenomic discovery of novel enzymes and biosurfactants in a slaughterhouse biofilm microbial community. AB - DNA derived from environmental samples is a rich source of novel bioactive molecules. The choice of the habitat to be sampled predefines the properties of the biomolecules to be discovered due to the physiological adaptation of the microbial community to the prevailing environmental conditions. We have constructed a metagenomic library in Escherichia coli DH10b with environmental DNA (eDNA) isolated from the microbial community of a slaughterhouse drain biofilm consisting mainly of species from the family Flavobacteriaceae. By functional screening of this library we have identified several lipases, proteases and two clones (SA343 and SA354) with biosurfactant and hemolytic activities. Sequence analysis of the respective eDNA fragments and subsequent structure homology modelling identified genes encoding putative N-acyl amino acid synthases with a unique two-domain organisation. The produced biosurfactants were identified by NMR spectroscopy as N-acyltyrosines with N-myristoyltyrosine as the predominant species. Critical micelle concentration and reduction of surface tension were similar to those of chemically synthesised N-myristoyltyrosine. Furthermore, we showed that the newly isolated N-acyltyrosines exhibit antibiotic activity against various bacteria. This is the first report describing the successful application of functional high-throughput screening assays for the identification of biosurfactant producing clones within a metagenomic library. PMID- 27271536 TI - Risk for Patient Harm in Canadian Genetic Counseling Practice: It's Time to Consider Regulation. AB - With the increasing awareness of genetic contributions to disease in Canada, the availability of and demand for genetic testing has soared. Genetic counseling is becoming a recognized and rapidly growing (yet unregulated) health profession in Canada. We hypothesized that the potential risk for harm to the public posed by genetic counseling practice in the province of Ontario is sufficient to consider regulation. The Ontario Ministry of Health and Long-Term Care (MOHTLC) sets criteria (both primary and secondary) to identify health professional bodies that meet the threshold for regulation in the province. We developed a survey based on the MOHTLC criteria to determine if genetic counselors meet the primary criteria to be considered for health professions regulation in Ontario. We surveyed 120 Ontario genetic counselors about their clinical practice and perceptions of risk for harm to the public. Results indicate that Ontario genetic counselors are highly independent in their clinical practice and are involved in patient care activities, clinical judgement and decision-making that have the potential to harm patients. In particular, cancer genetic counselors were identified as a cohort that practices with relatively high autonomy and low supervision. In summary, our study indicates that genetic counseling practice in Ontario meets the primary criteria to be considered for regulation. PMID- 27271537 TI - Midterm outcomes of catheter-directed interventions for the treatment of acute pulmonary embolism. AB - Objective The hemodynamic benefits of catheter-directed thrombolysis for acute pulmonary embolism have not been clearly defined beyond the periprocedural period. The objective of this study is to report midterm outcomes of catheter directed thrombolysis for treatment of acute pulmonary embolism. Methods Records of all patients undergoing catheter-directed thrombolysis for high- or intermediate-risk pulmonary embolism were retrospectively reviewed. Endpoints were clinical success, procedure-related complications, mortality, and longitudinal echocardiographic parameter improvement. Results A total of 69 patients underwent catheter-directed thrombolysis (mean age 59 +/- 15 y, 56% male). Eleven had high-risk and 58 intermediate-risk pulmonary embolism. Baseline characteristics did not differ by pulmonary embolism subtype. Fifty-two percent of patients underwent ultrasound-assisted thrombolysis, 39% standard catheter directed thrombolysis, and 9% other interventional therapy; 89.9% had bilateral treatment. Average treatment time was 17.7 +/- 11.3 h with average t-Pa dose of 28.5 +/- 19.6 mg. The rate of clinical success was 88%. There were two major (3%) and six minor (9%) periprocedural bleeding complications with no strokes. All echocardiographic parameters demonstrated significant improvement at one-year follow-up. Pulmonary embolism-related in-hospital mortality was 3.3%, and estimated survival was 81.2% at one year. Conclusions Catheter-directed thrombolysis is safe and effective for treatment of acute pulmonary embolism, with sustained hemodynamic improvement at one year. Further prospective large scale studies are needed to determine comparative effectiveness of interventions for acute pulmonary embolism. PMID- 27271539 TI - The high price of public fear of low-dose radiation. PMID- 27271538 TI - Purification of Nanoparticles by Size and Shape. AB - Producing monodisperse nanoparticles is essential to ensure consistency in biological experiments and to enable a smooth translation into the clinic. Purification of samples into discrete sizes and shapes may not only improve sample quality, but also provide us with the tools to understand which physical properties of nanoparticles are beneficial for a drug delivery vector. In this study, using polymersomes as a model system, we explore four techniques for purifying pre-formed nanoparticles into discrete fractions based on their size, shape or density. We show that these techniques can successfully separate polymersomes into monodisperse fractions. PMID- 27271540 TI - How I Do It: Hybrid Laparoscopic and Robotic Pancreaticoduodenectomy. AB - Minimally invasive pancreatic resections remain technically challenging. Distal pancreatectomy has been embraced at multiple centers as an acceptable minimally invasive technique in selected patients. In contrast, minimally invasive pancreaticoduodenectomy has not achieved broad acceptance, partly due to technical challenges. We detail a minimally invasive technique that utilizes both laparoscopic and robotic approaches which capitalizes on the advantages of each. Our early results have encouraged the continued development of this minimally invasive pancreatic surgery program. This hybrid technique may be an approach that is useful for surgeons striving to adopt the advantages of minimally invasive surgery for their patients. PMID- 27271541 TI - Esophageal Apoplexy. AB - Oesophageal apoplexy or intramural haematoma of the oesophagus (IHE) is a rare condition with a pattern of presentation that can mimic sinister pathologies. Diagnosis requires a high index of suspicion, and the exclusion of an oesophageal perforation or oesophageal malignancy is important. Investigations include computer topography (CT) and contrast swallow studies as well as a gastroscopy. Management is mainly supportive with resolution of symptoms typically occurring rapidly. We present two cases of this rare condition, with accompanying images. PMID- 27271542 TI - Narrating positive versus negative memories of illness: does narrating influence the emotional tone of memories? AB - Psychoncological studies have recognised a reduced autobiographical memory in cancer patients, furthermore cognitive studies have found that narrative is an effective instrument to re-elaborate memories. However, it is still unclear whether narrating positive versus negative events can have a different impact on autobiographical memory. The present study aims to explore the emotional experience of autobiographical memory before and after having narrated negative or positive events related to the illness. Of 63 oncological patients, 35 were selected for the present study. Participants completed a Memory Fluency Task twice, before and after having selected and narrated a positive (PN group) or a negative (NN group) memory of illness. They also had to attribute one or more emotions to each memory and to the narrative. The number of emotions and the percentage of emotional tones in both narrated and non-narrated memories were assessed. Narrated memories were more emotionally re-elaborated than non-narrated ones. Negative group participants, more than positive group ones, decreased negative emotions and increased complex ones. Authors discuss these results claiming that narrating works as a rehearsal of autobiographical memories in oncological patients and narrating negative memories eases the emotional re elaboration of illness. PMID- 27271543 TI - Neuropeptide derivatives to regulate the reproductive axis: Kisspeptin receptor (KISS1R) ligands and neurokinin-3 receptor (NK3R) ligands. AB - Recent research has indicated pivotal roles for neuropeptides and their cognate receptors in reproductive physiology. Kisspeptins are RF-amide neuropeptides that stimulate gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. Neurokinin B (NKB) is a member of the tachykinin family of neuropeptides and positively regulates pulsatile GnRH secretion. These peptides are coexpressed in kisspeptin/NKB/Dyn (KNDy) neurons of the arcuate nucleus, where they contribute to the regulation of puberty onset and other reproductive functions. In this review, the design of peptide ligands for the kisspeptin (KISS1R) and neurokinin 3 (NK3R) receptors are described. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 588-597, 2016. PMID- 27271544 TI - Posttraumatic Stress Disorder after Vaginal Delivery at Primiparous Women. AB - Although severe gynaecological pathology during delivery and negative outcome have been shown to be related with posttraumatic stress disorder (PTSD) little is known about traumatic experiences following regular delivery, at the expected time and with a healthy child. The objective of our study was to determine the prevalence of PTSD during postpartum period after vaginal delivery and its risk factors. The sample included 126 primiparous women. Monthly, for the next three months, the women were assessed for PTSD using the gold standard interview for PTSD, Clinician-Administered PTSD Scale (CAPS). Risk factors were assessed including sociodemographic variables, personal medical history and clinical variables. After the first month, 2.4% women had acute full PTSD and another 9.5% had clinically significant level of PTSD symptoms. Following the second and the third month, partial PTSD was found in 5.9% and 1.3% of the women, respectively, and none of participants had full PTSD. Obstetrical interventions were the only significant risk factor for the development of PTSD. Symptoms of postpartum PTSD are not rare after a traumatic delivery, and associated with specific obstetrical risk factors. Awareness of these risk factors may stimulate interventions to prevent this important and neglected postpartum disorder. PMID- 27271546 TI - Hereditary angioedema with normal C1 inhibitor and factor XII mutation: a series of 57 patients from the French National Center of Reference for Angioedema. AB - Hereditary angioedema (HAE) is a rare disease associated with either a quantitative or qualitative deficiency in C1-inhibitor (C1-INH) or normal C1-INH. HAE with normal C1-INH is associated in 20% of cases with mutations in the gene for factor XII (FXII) or FXII-HAE. A recent review described 41 families, including 14 German and 15 Spanish families. We have constructed a register of French patients and their characteristics. A national survey was launched through the French National Center of Reference for Angioedema (CREAK) to study the clinical, biological and therapeutic characteristics of patients with HAE linked to a mutation of FXII gene. Fifty-seven patients were identified from 24 different families. In most cases they were young women (mean age at diagnosis: 31 years, mean age at first symptom: 21 years, female/male ratio: 76%). Twenty one per cent of the patients experienced angioedema attacks only during pregnancy or when on oestrogen contraception. Sixty-three per cent had attacks at all times, but they were more severe during these same periods. Male carriers of the mutation were more frequently asymptomatic than females (P = 0.003). C1-INH concentrate and icatibant were both effective for treating attacks. The prophylactic use of tranexamic acid led to a 64% decrease in the number of attacks. This is one of the largest series reported of HAE patients with FXII mutation. The therapeutic management appeared to be identical to that of HAE with C1-INH deficiency. PMID- 27271548 TI - Low Blood Arterial Oxygenation During Venovenous Extracorporeal Membrane Oxygenation: Proposal for a Rational Algorithm-Based Management. AB - PURPOSE: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapeutic option in the management of the most severe forms of acute respiratory distress syndrome. Oxygenation during VV-ECMO depends on many parameters, and its management is complex. The management of ECMO is still not completely codified. The aim of this study was to rationalize the management of hypoxemia during VV-ECMO. METHODS: To build a comprehensive flow diagram for management of hypoxemia during VV-ECMO, we considered (1) relationship between O2 arterial saturation and its determinants; (2) analysis of physiopathology of oxygenation under VV-ECMO; and (3) main guidelines and recommendations recapitulated in troubleshooting charts. RESULTS: We propose a stepwise approach that could guide specific intervention to improve oxygenation during VV-ECMO. The first step is to obtain adequate pump flow, the main determinant of oxygenation, by eliminating a mechanical problem or inadequate venous drainage. Second, if hypoxemia persists, algorithm considers multiple reasons for inadequate oxygenation, namely: (1) excessive recirculation, (2) excessive cardiac output (decrease of ratio pump flow/cardiac output), (3) decrease in SvO2 (oxygen saturation in mixed venous blood), (4) malfunction of oxygenator, and (5) deterioration of residual lung function. Finally, for each modification of oxygenation parameters, specific measures are proposed to restore an adequate oxygenation by extracorporeal membrane oxygenation. CONCLUSION: If hypoxemia occurs during VV-ECMO, collecting oxygenation parameters and a clear step-by-step algorithm could guide specific intervention to improve oxygenation. This flow diagram is in accordance with current recommendations recapitulated in guidelines or troubleshooting chart but more accurate and complete. Although rational and appealing, it remains to be tested together with a number of still unsolved issues. PMID- 27271547 TI - Carotenoid intake and adipose tissue carotenoid levels in relation to prostate cancer aggressiveness among African-American and European-American men in the North Carolina-Louisiana prostate cancer project (PCaP). AB - BACKGROUND: Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness. METHODS: Data on African-American (AA, n = 1,023) and European American (EA, n = 1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed-food frequency questionnaire (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. RESULTS: Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher beta-cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR = 0.55, 95%CI: 0.34-0.89, Ptrend = 0.02), while an inverse association was observed between dietary beta-cryptoxanthin intake and high aggressive CaP among AAs (OR = 0.56, 95%CI: 0.36-0.87, Ptrend = 0.01). Adipose tissue alpha-carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose alpha-carotene (Ptrend = 0.07) and lycopene (Ptrend = 0.11), and CaP aggressiveness among EAs only. CONCLUSIONS: These results suggest that diets high in lycopene and beta-cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the observed racial differences in associations. Prostate 76:1053-1066, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27271550 TI - Immunotherapy after hematopoietic stem cell transplantation using umbilical cord blood-derived products. AB - Umbilical cord blood (UCB) is being increasingly used as a source of hematopoietic stem cells (HSC) for transplantation. UCB transplantation (UCBT) has some advantages such as less stringent HLA-matching requirements, fast availability of the graft and reduced incidence and severity of graft-versus-host disease. However, UCBT is also associated with a higher incidence of infection, graft failure, slow engraftment and slow immune reconstitution. UCB is mainly used as a source of HSC; however, it is also rich in immune cells that could be used to treat some of the main complications post-UCBT as well as other diseases, thus implicating the use of UCB for immunotherapy. Here, we aim to describe some of the therapies currently developed that use UCB as a cell source, focusing in particular on regulatory T cells and natural killer cells. PMID- 27271549 TI - Uncoupling protein 2 regulates metabolic reprogramming and fate of antigen stimulated CD8+ T cells. AB - Adoptive cell therapy (ACT) employing ex vivo-generated tumor antigen-specific CD8+ T cells shows tumor efficacy when the transferred cells possess both effector and memory functions. New strategies based on understanding of mechanisms that balance CD8+ T cell differentiation toward effector and memory responses are highly desirable. Emerging information confirms a central role for antigen-induced metabolic reprogramming in CD8+ T cell differentiation and clonal expansion. The mitochondrial protein uncoupling protein 2 (UCP2) is induced by antigen stimulation of CD8+ T cells; however, its role in metabolic reprogramming underlying differentiation and clonal expansion has not been reported. Employing genetic (siRNA) and pharmacologic (Genipin) approaches, we note that antigen induced UCP2 expression reduces glycolysis, fatty acid synthesis and production of reactive oxygen species to balance differentiation with survival of effector CD8+ T cells. Inhibition of UCP2 promotes CD8+ T cell terminal differentiation into short-lived effector cells (CD62L(lo)KLRG1(Hi)IFNgamma(Hi)) that undergo clonal contraction. These findings are the first to reveal a role for antigen induced UCP2 expression in balancing CD8+ T cell differentiation and survival. Targeting UCP2 to regulate metabolic reprogramming of CD8+ T cells is an attractive new approach to augment efficacy of tumor therapy by ACT. PMID- 27271551 TI - Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection. AB - Interactions between pancreatic cancer cells and inflammatory cells play crucial roles in the biological behavior of pancreatic cancer. Abundant infiltration of immunoglobulin G4 (IgG4)-positive plasma cells in the pancreas is the most significant feature of autoimmune pancreatitis; however, the clinical significance of IgG4-positive plasma cell infiltration in pancreatic cancer has not previously been reported. Herein, we analyzed intratumoral and peritumoral infiltrations of IgG4-positive plasma cells in 95 pancreatic cancer cases after curative resection. The correlations between IgG4-positive plasma cell infiltration and the clinicopathologic traits and overall survival of pancreatic cancer were investigated. IgG4-positive plasma cells were found in 86 % of tumor tissue samples compared with 69 % of peritumoral tissue samples (P = 0.0063). The high-level infiltration of intratumoral IgG4-positive plasma cells was positively correlated with poor histological grade (P = 0.017). The high-level infiltration of intratumoral IgG4-positive plasma cells was significantly correlated with worse prognosis (P = 0.01) in multivariate analysis. We further found that intratumoral M2-polarized tumor-associated macrophages (TAMs) were positively, linearly correlated with IgG4-positive plasma cells. In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells. PMID- 27271553 TI - Esophageal squamous papillomatosis. PMID- 27271552 TI - Update on the role of molecular factors and fibroblasts in the pathogenesis of Dupuytren's disease. AB - The mechanism by which the fibroblast is able to trigger palmar fibromatosis is still not yet fully understood. It would appear certain that the "abnormal" fibroblasts continuously synthesise profibrotic cytokines which are able to determine the activation to myofibroblasts, to stimulate them to the further proliferation and synthesis of other cytokines, to modify the cells' differentiation and ultrastructural characteristics, as well as the production of matrix and other proteins. Several fibroblast growth factors have been suggested to be responsible of an abnormal cell activation with an aberrantly elevated collagen synthesis and extracellular deposition in Dupuytren's disease, as TGF Beta, TNF-Alfa, PDGF, GM-CSF, free radicals, metalloproteinases, sex hormones, gene modified expression, mechanical stimulation. The Authors review the current state of knowledge in the field, by analyzing the role of these cytokines in the palmar fibromatosis. PMID- 27271554 TI - Radiofrequency catheter ablation versus balloon cryoablation of atrial fibrillation: markers of myocardial damage, inflammation, and thrombogenesis. AB - BACKGROUND: Evidence from animal and human studies suggests that cryoablation might be associated with a lesser inflammatory response and activation of coagulation compared with radiofrequency ablation. The study was aimed at comparing the effect of cryoballoon and radiofrequency catheter ablation of paroxysmal atrial fibrillation on markers of myocardial damage, inflammation, and activation of coagulation. METHODS: Forty-one patients received either cryoballoon (n = 23) or radiofrequency (n = 18) ablation of atrial fibrillation. We measured troponin I, high-sensitivity CRP, and interleukin 6 at baseline from the cubital vein, and from the right and left atrium before and after ablation, and from the cubital vein the following day. Prothrombin fragments 1 + 2, soluble P-selectin, and D-dimer were measured before and after ablation from both atria. RESULTS: We observed higher troponin I release in the cryoballoon than in the radiofrequency group (7.01 mcg/l (interquartile range [IQR]: 5.30-9.09) vs 2.32 mcg/l (IQR: 1.45-2.98), p < 0.001). The levels of inflammatory markers (high sensitivity CRP and interleukin 6) in the two groups were comparable, as were the levels of markers of coagulation activation. Procedure duration, fluoroscopy times, and mid-term success (23 months, IQR 7-32) of the two groups were also comparable. CONCLUSIONS: Cryoballoon ablation of atrial fibrillation causes more significant myocardial damage, that is, more extensive ablation lesions, compared with radiofrequency catheter ablation. However, no major differences between these two ablation techniques with regard to the inflammatory response and activation of the coagulation system were observed. PMID- 27271555 TI - Exploring substrate scope and stereoselectivity of P450 peroxygenase OleTJE in olefin-forming oxidative decarboxylation. AB - As recently reported, the olefin-forming oxidative decarboxylation of straight chain C4-C22 carboxylic acids catalyzed by P450 peroxygenase OleTJE constitutes a mild alkene synthesis. The present study shows that structurally different carboxylic acids are also accepted, including those that generate di-substituted olefins. Exploratory mutational experiments lead to increased trans-selectivity. PMID- 27271557 TI - Rapid identification of fruit length loci in cucumber (Cucumis sativus L.) using next-generation sequencing (NGS)-based QTL analysis. AB - The cucumber (Cucumis sativus L.) exhibits extensive variations in fruit size and shape. Fruit length is an important agronomic and domesticated trait controlled by quantitative trait loci (QTLs). Nonetheless, the underlying molecular and genetic mechanisms that determine cucumber fruit length remain unclear. QTL-seq is an efficient strategy for QTL identification that takes advantage of bulked segregant analysis (BSA) and next-generation sequencing (NGS). In the present study, we conducted QTL mapping and QTL-seq of cucumber fruit length. QTL mapping identified 8 QTLs for immature and mature fruit length. A major-effect QTL fl3.2, which explained a maximum of 38.87% of the phenotypic variation, was detected. A genome-wide comparison of SNP profiles between two DNA bulks identified 6 QTLs for ovary length. QTLs ovl3.1 and ovl3.2 both had major effects on ovary length with a ? (SNP-index) of 0.80 (P < 0.01) and 0.74 (P < 0.01), respectively. Quantitative RT-PCR of fruit size-related homologous genes localized in the consensus QTL FL3.2 was conducted. Four candidate genes exhibited increased expression levels in long fruit genotypes. Our results demonstrated the power of the QTL-seq method in rapid QTL detection and provided reliable QTL regions for fine mapping of fruit length-related loci and for identifying candidate genes. PMID- 27271558 TI - 2016 New talent Americas across academia and the U.S. National Laboratories. PMID- 27271556 TI - Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury. AB - Acute kidney injury (AKI) is an abrupt reduction in kidney function caused by different pathological processes. It is associated with a significant morbidity and mortality in the acute phase and an increased risk of developing End Stage Renal Disease. Despite the progress in the management of the disease, mortality rates in the last five decades remain unchanged at around 50%. Therefore there is an urgent need to find new therapeutic strategies to treat AKI. Lysosomal proteases, particularly Cathepsin D (CtsD), play multiple roles in apoptosis however, their role in AKI is still unknown. Here we describe a novel role for CtsD in AKI. CtsD expression was upregulated in damaged tubular cells in nephrotoxic and ischemia reperfusion (IRI) induced AKI. CtsD inhibition using Pepstatin A led to an improvement in kidney function, a reduction in apoptosis and a decrease in tubular cell damage in kidneys with nephrotoxic or IRI induced AKI. Pepstatin A treatment slowed interstitial fibrosis progression following IRI induced AKI. Renal transplant biopsies with acute tubular necrosis demonstrated high levels of CtsD in damaged tubular cells. These results support a role for CtsD in apoptosis during AKI opening new avenues for the treatment of AKI by targeting lysosomal proteases. PMID- 27271560 TI - Asn47 and Phe114 modulate the inner sphere reorganization energies of type zero copper proteins. AB - The geometric structures and electron transfer properties of type 1 Cu proteins are reasonably understood at the molecular level (E. I. Solomon and R. G. Hadt, Coord. Chem. Rev., 2011, 255, 774-789, J. J. Warren, K. M. Lancaster, J. H. Richards and H. B. Gray, J. Inorg. Biochem., 2012, 115, 119-126). Much understanding of type 1 copper electron transfer reactivity has come from site directed mutagenesis studies. For example, artificial "type zero" Cu-centres constructed in cupredoxin-azurin have showcased the capacity of outer-sphere hydrogen bonding networks to enhance Cu II/I electron transfer reactivity. In this paper, we have elaborated on earlier kinetics and electronic structural studies of type zero Cu by calculating the inner sphere reorganization energies of type 1, type 2, and type zero Cu proteins using density functional theory (DFT). Although the choice of density functionals for copper systems is not straightforward, we have benchmarked the density functionals against the recently reported ESI-PES data for two synthetic copper models (S. Niu, D.-L. Huang, P. D. Dau, H.-T. Liu, L.-S. Wang and T. J. Ichiye, Chem. Theory Comput., 2014, 10, 1283). For the Cu proteins, our calculations predict that changes in the coordination number upon metal reduction lead to large inner sphere reorganization energies for type 2 Cu sites, whereas retention in the coordination number is observed for type zero Cu sites. These variations in the coordination number are modulated by the outer-sphere coordinating residues Asn47 and Phe114, which are involved in hydrogen bonding with the Asp112 side chain. PMID- 27271559 TI - Cholera Toxin Promotes Th17 Cell Differentiation by Modulating Expression of Polarizing Cytokines and the Antigen-Presenting Potential of Dendritic Cells. AB - Cholera toxin (CT), an exotoxin produced by Vibrio cholera, acts as a mucosal adjuvant. In a previous study, we showed that CT skews differentiation of CD4 T cells to IL-17-producing Th17 cells. Here, we found that intranasal administration of CT induced migration of migratory dendritic cell (DC) populations, CD103+ DCs and CD11bhi DCs, to the lung draining mediastinal lymph nodes (medLN). Among those DC subsets, CD11bhi DCs that were relatively immature had a major role in Th17 cell differentiation after administration of CT. CT treated BMDCs showed reduced expression of MHC class II and CD86, similar to CD11bhi DCs in medLN, and these BMDCs promoted Th17 cell differentiation more potently than other BMDCs expressing higher levels of MHC class II and CD86. By analyzing the expression of activation markers such as CD25 and CD69, proliferation and IL-2 production, we determined that CT-treated BMDCs showed diminished antigen-presenting potential to CD4+ T cells compared with normal BMDCs. We also found that CT-stimulated BMDCs promote activin A expression as well as IL-6 and IL-1beta, and activin A had a synergic role with TGF-beta1 in CT mediated Th17 cell differentiation. Taken together, our results suggest that CT stimulated DCs promote Th17 cell differentiation by not only modulating antigen presenting potential but also inducing Th polarizing cytokines. PMID- 27271561 TI - Correction: Adipose Tissue-Derived Mesenchymal Stem Cells in Long-Term Dialysis Patients Display Downregulation of PCAF Expression and Poor Angiogenesis Activation. AB - [This corrects the article DOI: 10.1371/journal.pone.0102311.]. PMID- 27271562 TI - Emergency care. PMID- 27271564 TI - Neprilysin Inhibition as a PARADIGM Shift in Heart Failure Therapy. AB - Heart failure is a growing global public health problem. With the aging population, increased risk factors for heart failure development, and better survival after myocardial infarction, the prevalence is only expected to increase in the coming years. Although existing therapies have improved the clinical course of heart failure patients, new approaches are urgently needed to enhance quality of life and reduce morbidity and mortality. However, there has been little progress in the treatment of chronic heart failure in the past decade with only two new drugs approved by the US FDA over this time. Better understanding of the neurohormonal axis of heart failure has lead to the development of LCZ696, a first-in-class novel agent that acts as an angiotensin receptor blocker and neprilysin inhibitor. In the PARADIGM-HF study, LCZ696 was superior to an angiotensin-converting enzyme inhibitor in reducing mortality and HF hospitalizations and improving quality of life across a broad spectrum of symptomatic patients with heart failure with reduced ejection fraction. While evaluation of long-term effects is still needed, the completed trials on LCZ696 demonstrate that the drug is generally well-tolerated with a safe side effect profile. LCZ696 should be strongly considered as a favorable alternative to angiotensin converting enzyme inhibitors and angiotensin receptor blockers in appropriate heart failure patients. PMID- 27271563 TI - Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure. AB - Heart failure (HF) patients suffer from exercise intolerance that diminishes their ability to perform normal activities of daily living and hence compromises their quality of life. This is due largely to detrimental changes in skeletal muscle mass, structure, metabolism, and function. This includes an impairment of muscle contractile performance, i.e., a decline in the maximal force, speed, and power of muscle shortening. Although numerous mechanisms underlie this reduction in contractility, one contributing factor may be a decrease in nitric oxide (NO) bioavailability. Consistent with this, recent data demonstrate that acute ingestion of NO3 (-)-rich beetroot juice, a source of NO via the NO synthase independent enterosalivary pathway, markedly increases maximal muscle speed and power in HF patients. This review discusses the role of muscle contractile dysfunction in the exercise intolerance characteristic of HF, and the evidence that dietary NO3 (-) supplementation may represent a novel and simple therapy for this currently underappreciated problem. PMID- 27271566 TI - Plasticity of Th17 Cells in Autoimmune Kidney Diseases. AB - The ability of CD4(+) T cells to differentiate into pathogenic Th1 and Th17 or protective T regulatory cells plays a pivotal role in the pathogenesis of autoimmune diseases. Recent data suggest that CD4(+) T cell subsets display a considerable plasticity. This plasticity seems to be a critical factor for their pathogenicity, but also for the potential transition of pathogenic effector T cells toward a more tolerogenic phenotype. The aim of the current study was to analyze the plasticity of Th17 cells in a mouse model of acute crescentic glomerulonephritis and in a mouse chronic model of lupus nephritis. By transferring in vitro generated, highly purified Th17 cells and by using IL-17A fate reporter mice, we demonstrate that Th17 cells fail to acquire substantial expression of the Th1 and Th2 signature cytokines IFN-gamma and IL-13, respectively, or the T regulatory transcription factor Foxp3 throughout the course of renal inflammation. In an attempt to therapeutically break the stability of the Th17 phenotype in acute glomerulonephritis, we subjected nephritic mice to CD3-specific Ab treatment. Indeed, this treatment induced an immunoregulatory phenotype in Th17 cells, which was marked by high expression of IL-10 and attenuated renal tissue damage in acute glomerulonephritis. In summary, we show that Th17 cells display a minimum of plasticity in acute and chronic experimental glomerulonephritis and introduce anti-CD3 treatment as a tool to induce a regulatory phenotype in Th17 cells in the kidney that may be therapeutically exploited. PMID- 27271565 TI - Inverse Correlation between IL-10 and HIF-1alpha in Macrophages Infected with Histoplasma capsulatum. AB - Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that regulates metabolic and immune response genes in the setting of low oxygen tension and inflammation. We investigated the function of HIF-1alpha in the host response to Histoplasma capsulatum because granulomas induced by this pathogenic fungus develop hypoxic microenvironments during the early adaptive immune response. In this study, we demonstrated that myeloid HIF-1alpha-deficient mice exhibited elevated fungal burden during the innate immune response (prior to 7 d postinfection) as well as decreased survival in response to a sublethal inoculum of H. capsulatum The absence of myeloid HIF-1alpha did not alter immune cell recruitment to the lungs of infected animals but was associated with an elevation of the anti-inflammatory cytokine IL-10. Treatment with mAb to IL-10 restored protective immunity to the mutant mice. Macrophages (Mphis) constituted most IL 10-producing cells. Deletion of HIF-1alpha in neutrophils or dendritic cells did not alter fungal burden, thus implicating Mphis as the pivotal cell in host resistance. HIF-1alpha was stabilized in Mphis following infection. Increased activity of the transcription factor CREB in HIF-1alpha-deficient Mphis drove IL 10 production in response to H. capsulatum IL-10 inhibited Mphi control of fungal growth in response to the activating cytokine IFN-gamma. Thus, we identified a critical function for Mphi HIF-1alpha in tempering IL-10 production following infection. We established that transcriptional regulation of IL-10 by HIF-1alpha and CREB is critical for activation of Mphis by IFN-gamma and effective handling of H. capsulatum. PMID- 27271568 TI - Surfactant Protein A Prevents IFN-gamma/IFN-gamma Receptor Interaction and Attenuates Classical Activation of Human Alveolar Macrophages. AB - Lung surfactant protein A (SP-A) plays an important function in modulating inflammation in the lung. However, the exact role of SP-A and the mechanism by which SP-A affects IFN-gamma-induced activation of alveolar macrophages (aMphis) remains unknown. To address these questions, we studied the effect of human SP-A on rat and human aMphis stimulated with IFN-gamma, LPS, and combinations thereof and measured the induction of proinflammatory mediators as well as SP-A's ability to bind to IFN-gamma or IFN-gammaR1. We found that SP-A inhibited (IFN-gamma + LPS)-induced TNF-alpha, iNOS, and CXCL10 production by rat aMphis. When rat macrophages were stimulated with LPS and IFN-gamma separately, SP-A inhibited both LPS-induced signaling and IFN-gamma-elicited STAT1 phosphorylation. SP-A also decreased TNF-alpha and CXCL10 secretion by ex vivo-cultured human aMphis and M-CSF-derived macrophages stimulated by either LPS or IFN-gamma or both. Hence, SP-A inhibited upregulation of IFN-gamma-inducible genes (CXCL10, RARRES3, and ETV7) as well as STAT1 phosphorylation in human M-CSF-derived macrophages. In addition, we found that SP-A bound to human IFN-gamma (KD = 11 +/- 0.5 nM) in a Ca(2+)-dependent manner and prevented IFN-gamma interaction with IFN-gammaR1 on human aMphis. We conclude that SP-A inhibition of (IFN-gamma + LPS) stimulation is due to SP-A attenuation of both inflammatory agents and that the binding of SP A to IFN-gamma abrogates IFN-gamma effects on human macrophages, suppressing their classical activation and subsequent inflammatory response. PMID- 27271567 TI - HMBPP Analog Prodrugs Bypass Energy-Dependent Uptake To Promote Efficient BTN3A1 Mediated Malignant Cell Lysis by Vgamma9Vdelta2 T Lymphocyte Effectors. AB - Vgamma9Vdelta2 effector T cells lyse cells in response to phosphorus-containing small molecules, providing primates a unique route to remove infected or malignant cells. Yet, the triggering mechanisms remain ill defined. We examined lysis mediated by human Vgamma9Vdelta2 effector T cells in response to the naturally occurring (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) or a synthetic cell-permeable prodrug, bis (pivaloyloxymethyl) (E)-4-hydroxy-3-methyl but-2-enyl phosphonate. CD27(+)/CD45RA(-) Th1-like effector cells killed K562 target cells through a mechanism that could be enhanced by either compound or TCR Ab and blocked by Src inhibition or butyrophilin 3 isoform A1 (BTN3A1) disruption. Pretreatment at 4 degrees : C decreased HMBPP-induced lysis but did not reduce lysis induced by bis (pivaloyloxymethyl) (E)-4-hydroxy-3-methyl-but-2 enyl phosphonate. Together, our results show that internalization of HMBPP into target cells is required for BTN3A1-dependent lysis by Vgamma9Vdelta2 effector T cells. The enhanced activity of the prodrug analog is due to its ability to bypass the pathways required for entry of HMBPP. These findings support an inside out model of T cell triggering driven by small-molecule induction of BTN3A1. PMID- 27271571 TI - Medical students' use of Facebook for educational purposes. AB - Medical students use Facebook to interact with one another both socially and educationally. This study investigates how medical students in a UK medical school use Facebook to support their learning. In particular, it identifies the nature of their educational activities, and details their experiences of using an educational Facebook group. Twenty-four medical students who self-identified as being Facebook users were invited to focus groups to attain a general overview of Facebook use within an educational context. A textual analysis was then conducted on a small group of intercalating medical students who used a self-created Facebook group to supplement their learning. Five of these students participated in semi-structured interviews. Six common themes were generated. These included 'collaborative learning', 'strategic uses for the preparation for assessment', 'sharing experiences and providing support', 'creating and maintaining connections', 'personal planning and practical organization' and 'sharing and evaluating educational resources'. Evidence from this study shows that medical students are using Facebook informally to enhance their learning and undergraduate lives. Facebook has enabled students to create a supportive learning community amongst their peers. Medical educators wishing to capitalize on Facebook, as a platform for formal educational initiatives, should remain cautious of intruding on this peer online learning community. PMID- 27271569 TI - Constitutive Lck Activity Drives Sensitivity Differences between CD8+ Memory T Cell Subsets. AB - CD8(+) T cells develop increased sensitivity following Ag experience, and differences in sensitivity exist between T cell memory subsets. How differential TCR signaling between memory subsets contributes to sensitivity differences is unclear. We show in mouse effector memory T cells (TEM) that >50% of lymphocyte specific protein tyrosine kinase (Lck) exists in a constitutively active conformation, compared with <20% in central memory T cells (TCM). Immediately proximal to Lck signaling, we observed enhanced Zap-70 phosphorylation in TEM following TCR ligation compared with TCM Furthermore, we observed superior cytotoxic effector function in TEM compared with TCM, and we provide evidence that this results from a lower probability of TCM reaching threshold signaling owing to the decreased magnitude of TCR-proximal signaling. We provide evidence that the differences in Lck constitutive activity between CD8(+) TCM and TEM are due to differential regulation by SH2 domain-containing phosphatase-1 (Shp-1) and C-terminal Src kinase, and we use modeling of early TCR signaling to reveal the significance of these differences. We show that inhibition of Shp-1 results in increased constitutive Lck activity in TCM to levels similar to TEM, as well as increased cytotoxic effector function in TCM Collectively, this work demonstrates a role for constitutive Lck activity in controlling Ag sensitivity, and it suggests that differential activities of TCR-proximal signaling components may contribute to establishing the divergent effector properties of TCM and TEM. This work also identifies Shp-1 as a potential target to improve the cytotoxic effector functions of TCM for adoptive cell therapy applications. PMID- 27271570 TI - Transcriptional Profiling of Th2 Cells Identifies Pathogenic Features Associated with Asthma. AB - Allergic asthma and rhinitis are two common chronic allergic diseases that affect the lungs and nose, respectively. Both diseases share clinical and pathological features characteristic of excessive allergen-induced type 2 inflammation, orchestrated by memory CD4(+) T cells that produce type 2 cytokines (Th2 cells). However, a large majority of subjects with allergic rhinitis do not develop asthma, suggesting divergence in disease mechanisms. Because Th2 cells play a pathogenic role in both these diseases and are also present in healthy nonallergic subjects, we performed global transcriptional profiling to determine whether there are qualitative differences in Th2 cells from subjects with allergic asthma, rhinitis, and healthy controls. Th2 cells from asthmatic subjects expressed higher levels of several genes that promote their survival as well as alter their metabolic pathways to favor persistence at sites of allergic inflammation. In addition, genes that enhanced Th2 polarization and Th2 cytokine production were also upregulated in asthma. Several genes that oppose T cell activation were downregulated in asthma, suggesting enhanced activation potential of Th2 cells from asthmatic subjects. Many novel genes with poorly defined functions were also differentially expressed in asthma. Thus, our transcriptomic analysis of circulating Th2 cells has identified several molecules that are likely to confer pathogenic features to Th2 cells that are either unique or common to both asthma and rhinitis. PMID- 27271573 TI - Biomarkers Guided Treatment Strategies in Adult Patients with Asthma: Ready for the Clinical Field? AB - Asthma is a chronic inflammatory airways disorder mainly characterized by heterogeneity. In the more severe forms, a discordance often exists between symptoms and inflammation. Difficulty in managing asthma derives partly from the multiple phenotypes existing and our inability to recognize them. The use of non invasive, with main representative the fraction of exhaled nitric oxide, or semi invasive techniques such as induced sputum are effective tools that can help us to guide asthma treatment. In the latest years, several serum biomarkers related to asthmatic inflammation have been used for the better recognition of asthma sub phenotypes to achieve optimization of therapy and disease outcome. In patients with mild-moderate asthma, as well as patients with more severe asthma, the use of blood eosinophils revealed an acceptable accuracy for the prediction of airway eosinophilia indicating that in future studies may facilitate both individualized treatment and management of asthma. None of the above techniques have been incorporated in clinical practice although sputum eosinophils can be used in patients with severe asthma particularly in specialized centers with great experience. Of great interest are blood eosinophils since current data support their role either as tool for treatment selections or/and as a biomarker of airway eosinophilia. PMID- 27271572 TI - MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer. AB - Mucinous adenocarcinoma (MAC) represents a distinct histopathological entity of colorectal cancer (CRC), which is associated with disease progression and poor prognosis. Here, we found that expression levels of miR-205 and miR-373 were specifically upregulated only in patients with mucinous colon cancers, but not in CRC that lack mucinous components. To investigate the effects of miR-205 and miR 373 on intestinal epithelial cell (IEC) biology by gain- and loss-of-function experiments in a proof-of-concept approach, we chose previously established in vitro human Caco-2-based models of differentiated, non-invasive (expressing TLR4 wild-type; termed Caco-2[WT]) versus undifferentiated, invasive (expressing TLR4 mutant D299G; termed Caco-2[D299G]) IEC. Enterocyte-like Caco-2[WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in colorectal carcinoma-like Caco-2[D299G], thus resembling the miRNA expression pattern of paired normal versus tumor samples from MAC patients. Using stable transfection, we generated miR-205- or miR-373-expressing and miR-205- or miR-373-inhibiting subclones of these IEC lines. We found that introduction of miR-205 into Caco-2[WT] led to expansion of mucus-secreting goblet cell-like cells, which was associated with induction of KLF4, MUC2 and TGFbeta1 expression. Activation of miR-205 in Caco-2[WT] induced chemoresistance, while inhibition of miR-205 in Caco-2[D299G] promoted chemosensitivity. Caco-2[WT] overexpressing miR 373 showed mitotic abnormalities and underwent morphologic changes (loss of epithelial polarity, cytoskeletal reorganization, and junctional disruption) associated with epithelial-mesenchymal transition and progression to inflammation associated colonic carcinoma, which correlated with induction of phosphorylated STAT3 and N-CADHERIN expression. Functionally, introduction of miR-373 into Caco 2[WT] mediated loss of cell-cell adhesion and increased proliferation and invasion. Reversely, inhibition of miR-373 allowed mesenchymal IEC to regain epithelial properties, which correlated with absence of neoplastic progression. Using xenografts in mice demonstrated miR-373-mediated acceleration of malignant intestinal tumor growth. In conclusion, our results provide first evidence that miR-205 and miR-373 may differentially contribute to the aggressive phenotype of MAC in CRC. PMID- 27271574 TI - Improved PCR Amplification of Broad Spectrum GC DNA Templates. AB - Many applications in molecular biology can benefit from improved PCR amplification of DNA segments containing a wide range of GC content. Conventional PCR amplification of DNA sequences with regions of GC less than 30%, or higher than 70%, is complex due to secondary structures that block the DNA polymerase as well as mispriming and mis-annealing of the DNA. This complexity will often generate incomplete or nonspecific products that hamper downstream applications. In this study, we address multiplexed PCR amplification of DNA segments containing a wide range of GC content. In order to mitigate amplification complications due to high or low GC regions, we tested a combination of different PCR cycling conditions and chemical additives. To assess the fate of specific oligonucleotide (oligo) species with varying GC content in a multiplexed PCR, we developed a novel method of sequence analysis. Here we show that subcycling during the amplification process significantly improved amplification of short template pools (~200 bp), particularly when the template contained a low percent of GC. Furthermore, the combination of subcycling and 7-deaza-dGTP achieved efficient amplification of short templates ranging from 10-90% GC composition. Moreover, we found that 7-deaza-dGTP improved the amplification of longer products (~1000 bp). These methods provide an updated approach for PCR amplification of DNA segments containing a broad range of GC content. PMID- 27271575 TI - A rapidly progressive dementia case with pathological diagnosis of FTLD-UPS. PMID- 27271577 TI - Eriobotrya japonica Water Extract Characterization: An Inducer of Interferon Gamma Production Mainly by the JAK-STAT Pathway. AB - Eriobotrya japonica (Thunb.) Lindl. (Loquat) (EJ) has been used as a medicinal plant to treat chronic bronchitis, coughs, phlegm, high fever and gastro-enteric disorders. Since the traditional use of EJ is related to modulating inflammation processes, our earlier studies on EJ leaves were performed on the water extract to investigate specific cytokines' modulation. These earlier studies, however, have shown that EJ leaf water extract (WE) and the water phase (WP) induce cytokines' production in in vitro and in vivo models. Therefore, the aim of this study was to specify the group(s) of compounds in EJ leaves that have this immunomodulatory activity and their mechanism of action. WE was obtained from boiling the leaves followed by butanol extraction, yielding a butanol-water phase (WP). WP was then subjected to methanol:acetone fractionation, yielding upper (MAU) and lower (MAL) phases. For further fractionation, MAU was subjected to column chromatography followed by elution with ethanol:water (EW), methanol:ethanol (ME) and, lastly, acetone:water (AW), respectively, to reveal three sub-fractions; MAU-EW, MAU-ME and MAU-AW. MAU-AW significantly increased IFN-gamma production from unstimulated and stimulated mouse spleen cells, as well as CD3+ T cells and natural killer cells. Furthermore, the fold increase of IFN gamma production by MAU-AW was concentration dependent, higher than the parent extract or any of the other sub-fractions, and such an IFN-gamma increase was reversed by two JAK-STAT inhibitors. In addition, MALDI-TOF-MS analysis of the extracts and sub-fractions showed compounds with molecular weights of >500 Daltons. The MAU-AW sub-fraction contained more polar compounds, such as flavonol and caffeic glycosides. In conclusion, these polar compounds in the EJ extract are responsible for inducing IFN-gamma production. Further chemical elucidation is warranted to lead to a specific IFN-gamma inducer and an immunomodulator in polarizing immune cells and balancing immune responses in certain diseases. PMID- 27271578 TI - Poly (l-gamma-glutamylglutamine) Polymer Enhances Doxorubicin Accumulation in Multidrug Resistant Breast Cancer Cells. AB - BACKGROUND: Drug resistance is one of the bottlenecks of cancer chemotherapy in the clinic. Polymeric nanomedicine is one of the most promising strategies for overcoming poor chemotherapy responses due to the multidrug resistance (MDR). METHODS: In this study, a new polymer-based drug delivery system, poly (l-gamma glutamylglutamine)-doxorubicin (PGG-Dox) conjugate, was studied in both drug induced resistant human breast cancer MDA-MB-231/MDR cells and their parent human breast cancer MDA-MB-231 cells. The effect of PGG on facilitating the growth inhibition of Dox against multidrug resistant cells were investigated by evaluating the cytotoxicity of PGG-Dox conjugate, PGG/Dox unconjugated complex and free Dox on both cells. The underlying mechanisms in resistant cells were further studied via the intracellular traffic studies. RESULTS: Both conjugated and unconjugated PGG significantly increased Dox uptake, prolonged Dox retention and reduced Dox efflux in the MDA-MB-231/MDR cells. The PGG-Dox conjugate is taken up by tumor cells mainly by pinocytosis pathway, in which PGG-Dox conjugate containing vesicles are formed and enter the cells. CONCLUSIONS: This study indicated that both polymer-drug conjugate and unconjugated complex are promising strategies of overcoming resistance of anti-tumor drugs. PMID- 27271576 TI - Inside out: the role of nucleocytoplasmic transport in ALS and FTLD. AB - Neurodegenerative diseases are characterized by the presence of protein inclusions with a different protein content depending on the type of disease. Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are no exceptions to this common theme. In most ALS and FTLD cases, the predominant pathological species are RNA-binding proteins. Interestingly, these proteins are both depleted from their normal nuclear localization and aggregated in the cytoplasm. This key pathological feature has suggested a potential dual mechanism with both nuclear loss of function and cytoplasmic gain of function being at play. Yet, why and how this pathological cascade is initiated in most patients, and especially sporadic cases, is currently unresolved. Recent breakthroughs in C9orf72 ALS/FTLD disease models point at a pivotal role for the nuclear transport system in toxicity. To address whether defects in nuclear transport are indeed implicated in the disease, we reviewed two decades of ALS/FTLD literature and combined this with bioinformatic analyses. We find that both RNA-binding proteins and nuclear transport factors are key players in ALS/FTLD pathology. Moreover, our analyses suggest that disturbances in nucleocytoplasmic transport play a crucial initiating role in the disease, by bridging both nuclear loss and cytoplasmic gain of functions. These findings highlight this process as a novel and promising therapeutic target for ALS and FTLD. PMID- 27271579 TI - Aza-Henry Reactions on C-Alkyl Substituted Aldimines. AB - The reactivity of C-CH3 substituted N-protected aldimines in aza-Henry addition reactions was compared with that of the analogous trifluoromethylated compounds. C-Alkyl aldimines easily reacted with nitro alkanes under solvent-free conditions and in the absence of catalyst, despite being worse electrophiles than C-CF3 aldimines, they gave the aza-Henry addition only when ZrCl4 was added. The presence of a bulky group on the imine carbon deeply influenced the reactivity. PMID- 27271580 TI - Polyphenols from Erythrina crista-galli: Structures, Molecular Docking and Phytoestrogenic Activity. AB - OBJECTIVES: The current study aimed at exploring the secondary metabolites content of Erythrina crista-galli aqueous methanol extract and assessing its phytoestrogenic and cytoprotective activities. METHODS: Isolation of the compounds was carried out using conventional chromatographic techniques. The structures of the isolated compounds were elucidated based on the UV, NMR spectral data along with their mass-spectrometric analyses. The phytoestrogenic activity was evaluated in-silico and in vitro using the Arabidopsis thaliana pER8: GUS reporter assay and the proliferation-enhancing activity of MCF-7 cells. KEY FINDINGS: Phytochemical investigation of E. crista-galli aqueous methanol extract resulted in the isolation and identification of five flavonoids. The plant extract and its fractions showed significant estrogenic activities compared to controls. CONCLUSION: Five flavonoids were identified from E. crista-galli aqueous methanol extract. To the best of our knowledge, among these flavonoids, apigenin-7-O-rhamnosyl-6-C-glucoside was isolated for the first time from nature. Moreover, luteolin-6-C-glucoside was isolated for the first time from this plant. The plant revealed promising phytoestrogenic activities. This gives rationale to some of its pharmacological properties and suggests additional phytoestrogenic effects, which have not been reported yet. PMID- 27271581 TI - Effect of Steam Blanching and Drying on Phenolic Compounds of Litchi Pericarp. AB - The effects of different treatment methods on the stability and antioxidant capacity of the bioactive phenolic compounds of litchi pericarps were investigated. Fresh litchi pericarps were open air-dried, steam-blanched for 3 min in combination with hot air oven drying at 60 and 80 degrees C, and unblanched pericarps were dried in a hot air oven at 40, 60, 70 and 80 degrees C until equilibrium weight was reached. The total phenolic compounds, flavonoids, anthocyanins, proanthocyanidins and individual procyanidins, and antioxidant activity were analyzed. The combination of blanching and drying at 60 degrees C significantly (p < 0.05) improved the release of phenolic compounds, individual procyanidins, and the extracts' antioxidant capacity compared with the unblanched hot air oven-dried and open air-dried pericarps. Drying of fresh unblanched litchi pericarps in either open air or a hot air oven caused significant losses (p < 0.05) in phenolic compounds and individual procyanidins, leading to a reduction in the antioxidant activity. A similar increase, retention or reduction was reflected in flavonoids, proanthocyanidins and anthocyanins because they are sub-groups of phenolic compounds. Ferric reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryldydrazyl (DPPH) radical-scavenging capacity of the treated pericarps were significantly correlated (r >= 0.927, p < 0.01) with the total phenolic compounds. Thus, the combination of steam blanching and drying treatments of fresh litchi pericarps could produce a stable and dry litchi pericarp that maintains phenolic compounds and antioxidant capacity as a raw material for further recovery of the phytochemicals. PMID- 27271582 TI - Synthesis of Novel UV Absorbers Bisindolylmethanes and Investigation of Their Applications on Cotton-Based Textile Materials. AB - Nowadays modified textiles, especially UV-protective, antibacterial and antimicrobial ones, have become the focus of great interest. In this study, several new UV absorbers, bis(indolyl)methane derivatives, were synthesized and grafted onto polyvinyl alcohol polymer (PVA). Their application properties on cotton-based textile materials were determined; the UV protection factor values of the modified fabrics were measured (UPF); and the antibacterial features of the fabrics were tested. PMID- 27271583 TI - Aqueous Extract of Paris polyphylla (AEPP) Inhibits Ovarian Cancer via Suppression of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator (PGC) 1alpha. AB - Chemotherapy, a major approach was used in carcinoma treatment, always involves the development of drug resistance as well as side-effects that affect the quality of patients' lives. An association between epithelial-mesenchymal transition (EMT) and chemotherapy resistance was established recently. We demonstrate in this paper that the aqueous extract of Paris polyphylla (AEPP)-a traditional Chinese medicine-can be used in various cancer types for suppression of carcinogenesis. We evaluated the suppressions of EMT and mitochondrial activity by AEPP treatment in a high-glucose (HG) induced-human ovarian carcinoma cell line (OVCAR-3 cells). The mitochondrial morphology was investigated using MitoTracker Deep Red FM staining. Our results indicated that AEPP reduced the viability of OVCAR-3 cells considerably through induction of apoptosis. However, this inhibitory potential of AEPP was attenuated by HG induction in OVCAR-3 cells. The levels of estrogen-related receptor (ERR)-alpha activator and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha were elevated by HG induction, but were suppressed by AEPP treatment. Down-regulations of cell survival and EMT were oberved in OVCAR-3 cells through suppression of PGC 1alpha by AEPP treatment. These results were confirmed through PGC-1alpha knockdown and overexpression in OVCAR-3 cells. Thus, AEPP can be beneficial for treating ovarian cancer and has potential for development of an integrative cancer therapy against ovarian cancer proliferation, metastasis, and migration. PMID- 27271584 TI - Four New Monoterpenoid Glycosides from the Flower Buds of Magnolia biondii. AB - Four new monoterpenoid glycosides 1-4, named magnoliaterpenoid A-D, were isolated from a 50% aqueous acetone extract of flower buds of Magnolia biondii, along with one known compound, (1'R,3'S,5'R,8'S,2Z,4E)-dihydrophaseic acid 3-O-beta-d glucopyranoside (5). Their structures and relative configuration were identified by extensive spectroscopic analysis (IR, UV, MS, 1D and 2D NMR). The aglycones of these four new compounds possess seven-membered rings systems, which are very rare. A plausible biosynthetic route for the four new compounds was proposed via the biogenetic isoprene rule. Compounds 1, 2, 3, and 4 showed no antimicrobial activity at the concentration range of 1.95-250 ug/mL. PMID- 27271585 TI - Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines. AB - A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2 carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4 (2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3 dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5 amine using the B3LYP/6-31 G(d, p) method were found to agree well with their X ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications. PMID- 27271586 TI - Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress Induced Oxidative Stress in Escherichia coli. AB - Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs) have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH) and adenosine triphosphate (ATP) significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH), glutathione S-transferase (GST), super oxide dismutase (SOD), and catalase (CAT). These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and heat stress-induced oxidative damage in E. coli. Our results indicate that AuNPs may be effective antioxidants. However, further studies are needed to confirm the role of AuNPs as antioxidative agents, as well as their mechanism of action. PMID- 27271587 TI - Dioscin Induces Apoptosis in Human Cervical Carcinoma HeLa and SiHa Cells through ROS-Mediated DNA Damage and the Mitochondrial Signaling Pathway. AB - Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca(2+) levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS mediated DNA damage and the mitochondrial signaling pathway. PMID- 27271588 TI - Capsaicin Inhibited Aggressive Phenotypes through Downregulation of Tumor Associated NADH Oxidase (tNOX) by POU Domain Transcription Factor POU3F2. AB - Capsaicin has been reported to preferentially inhibit the activity of tumor associated NADH oxidase (tNOX), which belongs to a family of growth-related plasma membrane hydroquinone oxidases in cancer/transformed cells. The inhibitory effect of capsaicin on tNOX is associated with cell growth attenuation and apoptosis. However, no previous study has examined the transcriptional regulation of tNOX protein expression. Bioinformatic analysis has indicated that the tNOX promoter sequence harbors a binding motif for POU3F2, which is thought to play important roles in neuronal differentiation, melanocytes growth/differentiation and tumorigenesis. In this study, we found that capsaicin-mediated tNOX downregulation and cell migration inhibition were through POU3F2. The protein expression levels of POU3F2 and tNOX are positively correlated, and that overexpression of POU3F2 (and the corresponding upregulation of tNOX) enhanced the proliferation, migration and invasion in AGS (human gastric carcinoma) cells. In contrast, knockdown of POU3F2 downregulates tNOX, and the cancer phenotypes are affected. These findings not only shed light on the molecular mechanism of the anticancer properties of capsaicin, but also the transcription regulation of tNOX expression that may potentially explain how POU3F2 is associated with tumorigenesis. PMID- 27271589 TI - Solid Phase Formylation of N-Terminus Peptides. AB - Formylation of amino groups is a critical reaction involved in several biological processes including post-translational modification of histones. The addition of a formyl group (CHO) to the N-terminal end of a peptide chain generates biologically active molecules. N-formyl-peptides can be produced by different methods. We performed the N-formylation of two chemotactic hexapetides, Met1-Leu2 Lys3-Leu4-Ile5-Val6 and Met1-Met2-Tyr3-Ala4-Leu5-Phe6, carrying out the reaction directly on peptidyl-resin following pre-activation of formic acid with N,N dicyclohexylcarbodiimmide (DCC) in liquid phase. The overnight incubation at 4 degrees C resulted in a significant increase in production yields of formylated peptides compared to the reaction performed at room temperature. The method is consistently effective, rapid, and inexpensive. Moreover, the synthetic strategy can be applied for the formylation of all primary amines at N-terminus of peptide chains or amino groups of lysine side-chains in solid phase. PMID- 27271590 TI - New 30-Noroleanane Triterpenoid Saponins from Holboellia coriacea Diels. AB - Three new 30-noroleanane triterpenoid saponins, akebonoic acid 28-O-beta-d glucopyranosyl-(1''->6')-beta-d-glucopyranosyl ester (1), akebonoic acid 28-O (6''-O-caffeoyl)-beta-d-glucopyranosyl-(1''->6')-beta-d-glucopyranosyl ester (Holboelliside A, 2) and 3beta,20alpha,24-trihydroxy-29-norolean-12-en-28-oic acid 3-O-(6'-O-caffeoyl)-beta-d-glucopyranoside (Holboelliside B, 3) were isolated from the stems of Holboellia coriacea Diels, together with five known compounds, eupteleasaponin VIII (4), 3alpha-akebonoic acid (5), quinatic acid (6), 3beta-hydroxy-30-norhederagenin (7) and quinatoside A (8). The structures of these compounds were determined on the basis of spectral and chemical evidence. Compounds 1-5 were evaluated for their inhibitory activity against three human tumors HepG2, HCT116 and SGC-7901 cell lines in vitro. PMID- 27271591 TI - Melanoma Cells Can Adopt the Phenotype of Stromal Fibroblasts and Macrophages by Spontaneous Cell Fusion in Vitro. AB - After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells' nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments. PMID- 27271592 TI - Host Plants Identification for Adult Agrotis ipsilon, a Long-Distance Migratory Insect. AB - In this study, we determined the host relationship of Agrotis ipsilon moths by identifying pollen species adhering them during their long-distance migration. Pollen carried by A. ipsilon moths was collected from 2012 to 2014 on a small island in the center of the Bohai Strait, which is a seasonal migration pathway of this pest species. Genomic DNA of single pollen grains was amplified by using whole genome amplification technology, and a portion of the chloroplast rbcL sequence was then amplified from this material. Pollen species were identified by a combination of DNA barcoding and pollen morphology. We found 28 species of pollen from 18 families on the tested moths, mainly from Angiosperm, Dicotyledoneae. From this, we were able to determine that these moths visit woody plants more than herbaceous plants that they carry more pollen in the early and late stages of the migration season, and that the amounts of pollen transportation were related to moth sex, moth body part, and plant species. In general, 31% of female and 26% of male moths were found to be carrying pollen. Amounts of pollen on the proboscis was higher for female than male moths, while the reverse was true for pollen loads on the antennae. This work provides a new approach to study the interactions between noctuid moth and their host plants. Identification of plant hosts for adult moths furthers understanding of the coevolution processes between moths and their host plants. PMID- 27271594 TI - Toxicity of Pekinenin C from Euphorbia Pekinensis Radix on Rat Small Intestinal Crypt Epithelial Cell and Its Apoptotic Mechanism. AB - Pekinenin C is a casbane diterpenoid separated from the root of the traditional Chinese medicine, Euphorbia pekinensis Rupr., which is used as drug for the treatment of edema, ascites, and hydrothorax. Whereas pekinenin C exhibits severe cytotoxicity, the exact toxicity mechanism is unclear. In this study, the effects of pekinenin C on cell inhibition, cell cycle, and cell apoptosis were examined to explain its toxic mechanism. The proliferation of IEC-6 cells was accessed via MTT colorimetric assay after incubated with different concentrations of pekinenin C. Pekinenin C-treated IEC-6 cells labeled with RNase/PI and Annexin V/PI were analyzed by flow cytometric analyses for evaluation of cell cycle distribution and cell apoptosis, respectively. The apoptosis mechanism of pekinenin C on IEC-6 was investigated through assaying the activities of caspase-3, 8, 9 by enzyme linked immunosorbent assay (ELISA), protein expression of Bax, Bcl-2, apoptosis inducing factor (AIF), Apaf-1, Fas-associated death domain (FADD) and type 1 associated death domain (TRADD) by Western-blot, mRNA expression of Fas receptor (FasR), Fas ligand (FasL), tumor necrosis factor receptor (TNFR1) and NF-kappaB by RT-PCR. The results showed that pekinenin C has exhibited obvious IEC-6 cells toxicity and the IC50 value was 2.1 MUg.mL(-1). Typical apoptosis characteristics were observed under a transmission electron microscopy, and it was found that pekinenin C could cause G0/G1 phase arrest in IEC-6 cells in a dose-dependent manner and induce apoptosis of IEC-6 cells. Additionally, pekinenin C could increase the expressions of Bax, AIF, Apaf-1, FasR, FasL, TNFR1 and NF-kappaB, suppress the expression of Bcl-2, FADD and TRADD, then activate caspase-3, 8, 9 cascades, and at last result in apoptosis. These results demonstrated that pekinenin C effectively promoted cell apoptosis, and induced IEC-6 cells apoptosis through both the mitochondrial and death receptor pathways. PMID- 27271595 TI - PAMP Activity of Cerato-Platanin during Plant Interaction: An -Omic Approach. AB - Cerato-platanin (CP) is the founder of a fungal protein family consisting in non catalytic secreted proteins, which work as virulence factors and/or as elicitors of defense responses and systemic resistance, thus acting as PAMPs (pathogen associated molecular patterns). Moreover, CP has been defined an expansin-like protein showing the ability to weaken cellulose aggregates, like the canonical plant expansins do. Here, we deepen the knowledge on CP PAMP activity by the use of a multi-disciplinary approach: proteomic analysis, VOC (volatile organic compound) measurements, and gas exchange determination. The treatment of Arabidopsis with CP induces a differential profile either in protein expression or in VOC emission, as well changes in photosynthetic activity. In agreement with its role of defense activator, CP treatment induces down-expression of enzymes related to primary metabolism, such as RuBisCO, triosephosphate isomerase, and ATP-synthase, and reduces the photosynthesis rate. Conversely, CP increases expression of defense-related proteins and emission of some VOCs. Interestingly, CP exposure triggered the increase in enzymes involved in GSH metabolism and redox homeostasis (glutathione S-transferase, thioredoxin, Cys-peroxiredoxin, catalase) and in enzymes related to the "glucosinolate-myrosinase" system, which are the premise for synthesis of defence compounds, such as camalexin and some VOCs, respectively. The presented results are in agreement with the accepted role of CP as a PAMP and greatly increase the knowledge of plant primary defences induced by a purified fungal elicitor. PMID- 27271593 TI - Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis. AB - Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6-37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91-4.77), p < 0.001, n = 11 studies). Meta regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required. PMID- 27271596 TI - A 'High Risk' Lifestyle Pattern Is Associated with Metabolic Syndrome among Qatari Women of Reproductive Age: A Cross-Sectional National Study. AB - This study investigated the effect of lifestyle patterns, as a combination of diet, physical activity and smoking, on Metabolic Syndrome (MetS) among Qatari women of childbearing age (n = 418), a population group particularly vulnerable to the health sequela of this syndrome. Using data from the National WHO STEPwise survey conducted in Qatar in 2012, Principal Component Factor Analysis was performed to derive lifestyle patterns with survey variables related to the frequency of consumption of 13 foods/food groups, physical activity levels, and smoking status. MetS was diagnosed using ATPIII criteria. Three lifestyle patterns were identified: 'High Risk' pattern, characterized by intakes of fast foods, sweets and sugar sweetened beverages, in addition to lower levels of physical activity and higher smoking prevalence; 'Prudent' pattern, driven mainly by higher intakes of fruits, vegetables, fish, and whole grains; and 'Traditional' pattern which included beans, meat, dairy products, and a low prevalence of smoking. Among these three lifestyle patterns, only the 'High Risk' was associated with MetS, whereby subjects belonging to the third tertile of this pattern's score had 2.5 times the odds of MetS compared to those belonging to the first tertile. The findings of this study demonstrated the synergy among high risk behaviors among Qatari women in increasing the odds of MetS; the latter being a major risk factor for cardiovascular diseases. PMID- 27271597 TI - Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond. AB - Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the 'Warburg effect'. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases. PMID- 27271598 TI - Biochemical Engineering Approaches for Increasing Viability and Functionality of Probiotic Bacteria. AB - The literature presents a growing body of evidence demonstrating the positive effect of probiotics on health. Probiotic consumption levels are rising quickly in the world despite the fluctuation of their viability and functionality. Technological methods aiming at improving probiotic characteristics are thus highly wanted. However, microbial metabolic engineering toolbox is not available for this kind of application. On the other hand, basic microbiology teaches us that bacteria are able to exhibit adaptation to external stresses. It is known that adequately applied sub-lethal stress, i.e., controlled in amplitude and frequency at a given stage of the culture, is able to enhance microbial robustness. This property could be potentially used to improve the viability of probiotic bacteria, but some technical challenges still need to be overcome before any industrial implementation. This review paper investigates the different technical tools that can be used in order to define the proper condition for improving viability of probiotic bacteria and their implementation at the industrial scale. Based on the example of Bifidobacterium bifidum, potentialities for simultaneously improving viability, but also functionality of probiotics will be described. PMID- 27271599 TI - High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer. AB - Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four groups according to their DRC level: High (>3.8%) and low (<3.8%). The four groups consisted of BC patients with high (n = 35) and low (n = 43) DRC and controls with high (n = 39) and low (n = 36) DRC. Epidemiologic data were collected at initial BC diagnosis and almost five years after diagnosis. A significant difference in Let-7b expression was found in BC patients with high DRC versus the remaining groups (p < 0.001). Thus, our data reveal a possible role of Let-7b on DRC during breast carcinogenesis. Our study is innovative because it provides the first evidence that Let-7b may play role in DRC regulation (through the NER repair pathway) in BC. PMID- 27271600 TI - Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. AB - Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases with an extensive range of substrate specificities. Collectively, these enzymes are able to degrade various components of extracellular matrix (ECM) proteins. Based on their structure and substrate specificity, they can be categorized into five main subgroups, namely (1) collagenases (MMP-1, MMP-8 and MMP-13); (2) gelatinases (MMP-2 and MMP-9); (3) stromelysins (MMP-3, MMP-10 and MMP-11); (4) matrilysins (MMP-7 and MMP-26); and (5) membrane-type (MT) MMPs (MMP-14, MMP-15, and MMP-16). The alterations made to the ECM by MMPs might contribute in skin wrinkling, a characteristic of premature skin aging. In photocarcinogenesis, degradation of ECM is the initial step towards tumor cell invasion, to invade both the basement membrane and the surrounding stroma that mainly comprises fibrillar collagens. Additionally, MMPs are involved in angiogenesis, which promotes cancer cell growth and migration. In this review, we focus on the present knowledge about premature skin aging and skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, with our main focus on members of the MMP family and their functions. PMID- 27271602 TI - v-Src Causes Chromosome Bridges in a Caffeine-Sensitive Manner by Generating DNA Damage. AB - An increase in Src activity is commonly observed in epithelial cancers. Aberrant activation of the kinase activity is associated with malignant progression. However, the mechanisms that underlie the Src-induced malignant progression of cancer are not completely understood. We show here that v-Src, an oncogene that was first identified from a Rous sarcoma virus and a mutant variant of c-Src, leads to an increase in the number of anaphase and telophase cells having chromosome bridges. v-Src increases the number of gammaH2AX foci, and this increase is inhibited by treatment with PP2, a Src kinase inhibitor. v-Src induces the phosphorylation of KAP1 at Ser824, Chk2 at Thr68, and Chk1 at Ser345, suggesting the activation of the ATM/ATR pathway. Caffeine decreases the number of cells having chromosome bridges at a concentration incapable of inhibiting Chk1 phosphorylation at Ser345. These results suggest that v-Src induces chromosome bridges via generation of DNA damage and the subsequent DNA damage response, possibly by homologous recombination. A chromosome bridge gives rise to the accumulation of DNA damage directly through chromosome breakage and indirectly through cytokinesis failure-induced multinucleation. We propose that v Src-induced chromosome bridge formation is one of the causes of the v-Src-induced malignant progression of cancer cells. PMID- 27271603 TI - Dehydroeburicoic Acid from Antrodia camphorata Prevents the Diabetic and Dyslipidemic State via Modulation of Glucose Transporter 4, Peroxisome Proliferator-Activated Receptor alpha Expression and AMP-Activated Protein Kinase Phosphorylation in High-Fat-Fed Mice. AB - This study investigated the potential effects of dehydroeburicoic acid (TT), a triterpenoid compound from Antrodia camphorata, in vitro and examined the effects and mechanisms of TT on glucose and lipid homeostasis in high-fat-diet (HFD)-fed mice. The in vitro study examined the effects of a MeOH crude extract (CruE) of A. camphorata and Antcin K (AnK; the main constituent of fruiting body of this mushroom) on membrane glucose transporter 4 (GLUT4) and phospho-Akt in C2C12 myoblasts cells. The in vitro study demonstrated that treatment with CruE, AnK and TT increased the membrane levels of glucose transporter 4 (GLUT4) and phospho Akt at different concentrations. The animal experiments were performed for 12 weeks. Diabetic mice were randomly divided into six groups after 8 weeks of HFD induction and treated with daily oral gavage doses of TT (at three dose levels), fenofibrate (Feno) (at 0.25 g/kg body weight), metformin (Metf) (at 0.3 g/kg body weight) or vehicle for another 4 weeks while on an HFD diet. HFD-fed mice exhibited increased blood glucose levels. TT treatment dramatically lowered blood glucose levels by 34.2%~43.4%, which was comparable to the antidiabetic agent Metf (36.5%). TT-treated mice reduced the HFD-induced hyperglycemia, hypertriglyceridemia, hyperinsulinemia, hyperleptinemia, and hypercholesterolemia. Membrane levels of GLUT4 were significantly higher in CruE treated groups in vitro. Skeletal muscle membrane levels of GLUT4 were significantly higher in TT-treated mice. These groups of mice also displayed lower mRNA levels of glucose-6-phosphatase (G6 Pase), an inhibitor of hepatic glucose production. The combination of these agents produced a net hypoglycemic effect in TT-treated mice. TT treatment enhanced the expressions of hepatic and skeletal muscle AMP-activated protein kinase (AMPK) phosphorylation in mice. TT treated mice exhibited enhanced expression of hepatic fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor alpha (PPARalpha) and increased mRNA levels of carnitine palmitoyl transferase Ia (CPT-1a). These mice also exhibited decreased expression levels of lipogenic fatty acid synthase (FAS) in liver and adipose tissue and reduced mRNA levels of hepatic adipocyte fatty acid binding protein 2 (aP2) and glycerol-3-phosphate acyltransferase (GPAT). These alterations resulted in a reduction in fat stores within the liver and lower triglyceride levels in blood. Our results demonstrate that TT is an excellent therapeutic approach for the treatment of type 2 diabetes and hypertriglyceridemia. PMID- 27271601 TI - Mechanism of Action and Applications of Interleukin 24 in Immunotherapy. AB - Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24's signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL 20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in cytokine-mediated activities. After exogenous addition of IL-24, apoptosis is induced in tumor cells independently of the JAK/STAT pathway. We have shown that IL-24 binds to Sigma 1 Receptor and this event induces endoplasmic reticulum stress, calcium mobilization, reactive oxygen species generation, p38MAPK activity, and ceramide production. Here we review IL-24's role in autoimmunity, infectious disease response, wound repair, and vascular disease. Detailed understanding of the pleiotropic roles of IL-24 signaling can assist in the selection of more accurate therapeutic approaches, as well as targeting of appropriate cell types in treatment strategy development, and ultimately achieve desired therapeutic effects. PMID- 27271604 TI - Synthesis of New Hydrated Geranylphenols and in Vitro Antifungal Activity against Botrytis cinerea. AB - Geranylated hydroquinones and other geranylated compounds isolated from Aplydium species have shown interesting biological activities. This fact has prompted a number of studies where geranylated phenol derivatives have been synthesized in order to assay their bioactivities. In this work, we report the synthesis of a series of new hydrated geranylphenols using two different synthetic approaches and their inhibitory effects on the mycelial growth of Botrytis cinerea. Five new hydrated geranylphenols were obtained by direct coupling reaction between geraniol and phenol in dioxane/water and using BF3.Et2O as the catalyst or by the reaction of a geranylated phenol with BF3.Et2O. Two new geranylated quinones were also obtained. The synthesis and structural elucidation of all new compounds is presented. All hydrated geranylphenols efficiently inhibit the mycelial growth of B. cinerea. Their activity is higher than that observed for non-hydrated compounds. These results indicate that structural modification on the geranyl chain brings about an enhancement of the inhibition effect of geranylated phenol derivatives. PMID- 27271605 TI - Ras-Related Nuclear Protein Ran3B Gene Is Involved in Hormone Responses in the Embryogenic Callus of Dimocarpus longan Lour. AB - Ras-related guanosine triphosphate (GTP)-binding nuclear protein (Ran) GTPases function as molecular switches and regulate diverse cellular events in eukaryotes. Our previous work suggested that DlRan3B is active during longan (Dimocarpus longan Lour.) somatic embryogenesis (SE) processes. Herein, subcellular localization of DlRan3B was found to be localized in the nucleus and expression profiling of DlRan3B was performed during longan SE and after exposure to plant hormones (indoleacetic acid (IAA), gibberellin A3 (GA3), salicylic acid (SA), methyl jasmonte (MeJA), and abscisic acid (ABA)). We cloned and sequenced 1569 bp of 5'-flanking sequence of DlRan3B (GenBank: JQ279697). Bioinformatic analysis indicated that the promoter contained plant hormone-related regulatory elements. Deletion analysis and responses to hormones identified stimulative and repressive regulatory elements in the DlRan3B promoter. The key elements included those responding to auxin, gibberellin, SA, MeJA, and ABA. DlRan3B was located in the nucleus and accumulated in the late stage of longan SE. The expression of DlRan3B was significantly induced by IAA, GA3, and ABA, but suppressed by SA and MeJA. Promoter transcription was induced by IAA and GA3, but suppressed by SA. Thus, DlRan3B might participate in auxin, gibberellin, and ABA responses during longan late SE, and DlRan3B is involved in phytohormone responsiveness. PMID- 27271606 TI - The MicroRNA-21 in Autoimmune Diseases. AB - MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR 21 in treating patients with autoimmune disease. PMID- 27271607 TI - Involvement and Clinical Aspects of MicroRNA in Osteosarcoma. AB - Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents, but its pathogenesis has been difficult to establish because of its well-known heterogeneous nature. OS has been associated with genetic and cytogenetic abnormalities, which include function-impairing mutations in tumor suppressors and the activation of oncogenes. OS tumorigenesis has been linked to alterations of several genes characterized by a high level of genetic instability and recurrent DNA amplifications and deletions. MicroRNAs (miRNAs), 18-25 nucleotide noncoding RNAs, are critical for various biological processes like differentiation, cell growth and cell death. Dysregulation of miRNA expression leads to phenotypic and genotypic changes in cells, which leads to cancer. Studies on miRNAs have initiated a significant effect in both diagnosis and treatment of cancer. This review focuses on the current knowledge of clinical applications of miRNAs for the better diagnosis and management of OS. PMID- 27271608 TI - An Efficient, Versatile, and Safe Access to Supported Metallic Nanoparticles on Porous Silicon with Ionic Liquids. AB - The metallization of porous silicon (PSi) is generally realized through physical vapor deposition (PVD) or electrochemical processes using aqueous solutions. The former uses a strong vacuum and does not allow for a conformal deposition into the pores. In the latter, the water used as solvent causes oxidation of the silicon during the reduction of the salt precursors. Moreover, as PSi is hydrophobic, the metal penetration into the pores is restricted to the near surface region. Using a solution of organometallic (OM) precursors in ionic liquid (IL), we have developed an easy and efficient way to fully metallize the pores throughout the several-um-thick porous Si. This process affords supported metallic nanoparticles characterized by a narrow size distribution. This process is demonstrated for different metals (Pt, Pd, Cu, and Ru) and can probably be extended to other metals. Moreover, as no reducing agent is necessary (the decomposition in an argon atmosphere at 50 degrees C is fostered by surface silicon hydride groups borne by PSi), the safety and the cost of the process are improved. PMID- 27271609 TI - MicroRNA-31 Emerges as a Predictive Biomarker of Pathological Response and Outcome in Locally Advanced Rectal Cancer. AB - Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision has emerged as the standard treatment for locally advanced rectal cancer (LARC) patients. However, many cases do not respond to neoadjuvant CRT, suffering unnecessary toxicities and surgery delays. Thus, identification of predictive biomarkers for neoadjuvant CRT is a current clinical need. In the present study, microRNA-31 expression was measured in formalin-fixed paraffin-embedded (FFPE) biopsies from 78 patients diagnosed with LARC who were treated with neoadjuvant CRT. Then, the obtained results were correlated with clinical and pathological characteristics and outcome. High microRNA-31 (miR-31) levels were found overexpressed in 34.2% of cases. Its overexpression significantly predicted poor pathological response (p = 0.018) and worse overall survival (OS) (p = 0.008). The odds ratio for no pathological response among patients with miR-31 overexpression was 0.18 (Confidence Interval = 0.06 to 0.57; p = 0.003). Multivariate analysis corroborated the clinical impact of miR-31 in determining pathological response to neoadjuvant CRT as well as OS. Altogether, miR-31 quantification emerges as a novel valuable clinical tool to predict both pathological response and outcome in LARC patients. PMID- 27271610 TI - Hypoxia Inducible Factor 1 (HIF-1) Recruits Macrophage to Activate Pancreatic Stellate Cells in Pancreatic Ductal Adenocarcinoma. AB - Hypoxia inducible factor 1 (HIF-1) is a transcription factor composed of two subunits, namely, HIF-1alpha and HIF-1beta, in which HIF-1beta is constitutively expressed. HIF-1 upregulates several hypoxia-responsive proteins, including angiogenesis factors, glycolysis solution enzymes, and cell survival proteins. HIF-1 is also associated with the degree of inflammation in the tumor region, but the exact mechanism remains unclear. This study aims to identify the molecular mechanism of recruiting monocytes/macrophages by HIF-1alpha in pancreatic ductal adenocarcinoma (PDAC) and the effects of macrophages on pancreatic stellate cells (PSCs). Immunohistochemistry (IHC) was performed for cluster of differentiation 68 (CD68), HIF-1alpha, and chemical chemokines 2 (CCL2). Western blot, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), chromatin immunoprecipitation assay, and The Cancer Genome Atlas (TCGA) were used to verify the correlation between HIF-1alpha and CCL2 at protein and nucleic acid levels. Monocytes/macrophages were co-cultured with PSCs to observe their interaction. Samples showed significant correlation between CD68 and HIF-1alpha (t-test, p < 0.05). HIF-1alpha recruited monocytes/macrophages by promoting CCL2 secretion. Moreover, macrophages could accelerate the activation of PSCs. HIF-1alpha might promote inflammation and fibrosis of PDAC through CCL2 secretion, which may provide a novel target to treat PDAC patients. PMID- 27271611 TI - Inhaled Cadmium Oxide Nanoparticles: Their in Vivo Fate and Effect on Target Organs. AB - The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria and they also accumulated in the cytoplasmic vesicles. In livers, inhalation caused periportal inflammation and local hepatic necrosis. Only minor changes such as diffusely thickened filtration membrane with intramembranous electron dense deposits were observed in kidney. Taken together, inhaled CdO nanoparticles not only accumulated in lungs but they were also transported to other organs causing serious damage at tissue as well as cellular level. PMID- 27271613 TI - Transcriptional Profiling and miRNA-Target Network Analysis Identify Potential Biomarkers for Efficacy Evaluation of Fuzheng-Huayu Formula-Treated Hepatitis B Caused Liver Cirrhosis. AB - Fuzheng-Huayu (FZHY) formula has been found to have a satisfactory effect on hepatitis B-caused cirrhosis (HBC) treatment. However, the efficacy evaluation of FZHY is often challenging. In this study, a randomized, double-blind and placebo controlled trial was used to evaluate the therapeutic efficacy of FZHY in HBC treatment. In the trial, 35 medical indexes were detected, and 14 indexes had a statistically-significant difference before compared to after the trial. Importantly, the Child-Pugh score also demonstrated FZHY having therapeutic efficacy. Furthermore, the microRNA (miRNA) profiles of 12 serum samples were detected in FZHY groups, and 112 differential-expressed (DE) miRNAs were determined. Using predicted miRNA targets, 13 kernel miRNAs were identified from the established miRNA-target network. Subsequently, quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to validate the expression level of 13 identified miRNAs in the trials. The results showed that nine miRNAs have a statistically-significant difference before compared to after FZHY treatment. By means of a logistic regression model, a miRNA panel with hsa-miR-18a-5p, -326, 1182 and -193b-5p was established, and it can clearly improve the accuracy of the efficacy evaluation of FZHY. This study suggested that the particular miRNAs can act as potential biomarkers and obviously increase the diagnostic accuracy for drug evaluation in HBC treatment progression. PMID- 27271612 TI - Preventive Effects of Rhodiola rosea L. on Bleomycin-Induced Pulmonary Fibrosis in Rats. AB - Rhodiola rosea L. (RRL) possesses a wide range of pharmacological properties, including lung-protective activity, and has been utilized in folk medicine for several 100 years. However, the lung-protective mechanism remains unclear. This study investigated the possible lung-protective activity mechanism of RRL in a pulmonary fibrosis (PF) rat model. Lung fibrotic injury was induced in Sprague Dawley rats by single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg). The rats were administered 125, 250, or 500 mg/kg of a 95% ethanol extract of RRL for 28 days. The animals were killed to detect changes in body weight, serum levels of glutathione (GSH) and total superoxide dismutase (T SOD), as well as lung tissue hydroxyproline (HYP) content. Tumor necrosis factor alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), and interleukin 6 (IL-6) levels were measured in bronchoalveolar lavage fluid (BALF) by enzyme linked immunosorbent assay. Hematoxylin and eosin, Masson's trichrome, and immunohistochemical staining were performed to observe the histopathological changes in lung tissues. Additionally, target-related proteins were measured by Western blotting. RRL alleviated the loss of body weight induced by instilling BLM in PF rats, particularly at the 500 mg/kg per day dose. RRL reduced HYP (p < 0.01) and increased GSH and T-SOD contents. BALF levels of TNF-alpha, TGF-beta1, and IL-6 decreased significantly in the RRL-treated groups. Expression levels of matrix metalloproteinase-9 (MMP-9) and alpha-smooth muscle actin decreased significantly in a dose-dependent manner in response to RRL. Moreover, the levels of TGF-beta1 and tissue inhibitor of metalloproteinase-1 in lung tissues also decreased in the RRL-treated groups. RRL alleviated BLM-induced PF in rats. Our results reveal that the protective effects of RRL against fibrotic lung injury in rats are correlated with its anti-inflammatory, antioxidative, and anti-fibrotic properties. MMP-9 may play important roles in BLM-induced PF. PMID- 27271614 TI - Molecular Characterization of the Complete Genome of Three Basal-BR Isolates of Turnip mosaic virus Infecting Raphanus sativus in China. AB - Turnip mosaic virus (TuMV) infects crops of plant species in the family Brassicaceae worldwide. TuMV isolates were clustered to five lineages corresponding to basal-B, basal-BR, Asian-BR, world-B and OMs. Here, we determined the complete genome sequences of three TuMV basal-BR isolates infecting radish from Shandong and Jilin Provinces in China. Their genomes were all composed of 9833 nucleotides, excluding the 3'-terminal poly(A) tail. They contained two open reading frames (ORFs), with the large one encoding a polyprotein of 3164 amino acids and the small overlapping ORF encoding a PIPO protein of 61 amino acids, which contained the typically conserved motifs found in members of the genus Potyvirus. In pairwise comparison with 30 other TuMV genome sequences, these three isolates shared their highest identities with isolates from Eurasian countries (Germany, Italy, Turkey and China). Recombination analysis showed that the three isolates in this study had no "clear" recombination. The analyses of conserved amino acids changed between groups showed that the codons in the TuMV out group (OGp) and OMs group were the same at three codon sites (852, 1006, 1548), and the other TuMV groups (basal-B, basal-BR, Asian-BR, world-B) were different. This pattern suggests that the codon in the OMs progenitor did not change but that in the other TuMV groups the progenitor sequence did change at divergence. Genetic diversity analyses indicate that the PIPO gene was under the highest selection pressure and the selection pressure on P3N-PIPO and P3 was almost the same. It suggests that most of the selection pressure on P3 was probably imposed through P3N-PIPO. PMID- 27271615 TI - Development of EST Intron-Targeting SNP Markers for Panax ginseng and Their Application to Cultivar Authentication. AB - Panax ginseng is one of the most valuable medicinal plants in the Orient. The low level of genetic variation has limited the application of molecular markers for cultivar authentication and marker-assisted selection in cultivated ginseng. To exploit DNA polymorphism within ginseng cultivars, ginseng expressed sequence tags (ESTs) were searched against the potential intron polymorphism (PIP) database to predict the positions of introns. Intron-flanking primers were then designed in conserved exon regions and used to amplify across the more variable introns. Sequencing results showed that single nucleotide polymorphisms (SNPs), as well as indels, were detected in four EST-derived introns, and SNP markers specific to "Gopoong" and "K-1" were first reported in this study. Based on cultivar-specific SNP sites, allele-specific polymerase chain reaction (PCR) was conducted and proved to be effective for the authentication of ginseng cultivars. Additionally, the combination of a simple NaOH-Tris DNA isolation method and real time allele-specific PCR assay enabled the high throughput selection of cultivars from ginseng fields. The established real-time allele-specific PCR assay should be applied to molecular authentication and marker assisted selection of P. ginseng cultivars, and the EST intron-targeting strategy will provide a potential approach for marker development in species without whole genomic DNA sequence information. PMID- 27271617 TI - A Nonlinear Model for Gene-Based Gene-Environment Interaction. AB - A vast amount of literature has confirmed the role of gene-environment (G*E) interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP) and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects) are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR) model to understand the gene-based G*E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC) model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR) model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G*E interaction. PMID- 27271616 TI - Tetrapyrroles as Endogenous TSPO Ligands in Eukaryotes and Prokaryotes: Comparisons with Synthetic Ligands. AB - The 18 kDa translocator protein (TSPO) is highly 0conserved in eukaryotes and prokaryotes. Since its discovery in 1977, numerous studies established the TSPO's importance for life essential functions. For these studies, synthetic TSPO ligands typically are applied. Tetrapyrroles present endogenous ligands for the TSPO. Tetrapyrroles are also evolutionarily conserved and regulate multiple functions. TSPO and tetrapyrroles regulate each other. In animals TSPO tetrapyrrole interactions range from effects on embryonic development to metabolism, programmed cell death, response to stress, injury and disease, and even to life span extension. In animals TSPOs are primarily located in mitochondria. In plants TSPOs are also present in plastids, the nuclear fraction, the endoplasmic reticulum, and Golgi stacks. This may contribute to translocation of tetrapyrrole intermediates across organelles' membranes. As in animals, plant TSPO binds heme and protoporphyrin IX. TSPO-tetrapyrrole interactions in plants appear to relate to development as well as stress conditions, including salt tolerance, abscisic acid-induced stress, reactive oxygen species homeostasis, and finally cell death regulation. In bacteria, TSPO is important for switching from aerobic to anaerobic metabolism, including the regulation of photosynthesis. As in mitochondria, in bacteria TSPO is located in the outer membrane. TSPO tetrapyrrole interactions may be part of the establishment of the bacterial eukaryote relationships, i.e., mitochondrial-eukaryote and plastid-plant endosymbiotic relationships. PMID- 27271618 TI - Regulation of Small RNAs and Corresponding Targets in Nod Factor-Induced Phaseolus vulgaris Root Hair Cells. AB - A genome-wide analysis identified the set of small RNAs (sRNAs) from the agronomical important legume Phaseolus vulgaris (common bean), including novel P. vulgaris-specific microRNAs (miRNAs) potentially important for the regulation of the rhizobia-symbiotic process. Generally, novel miRNAs are difficult to identify and study because they are very lowly expressed in a tissue- or cell-specific manner. In this work, we aimed to analyze sRNAs from common bean root hairs (RH), a single-cell model, induced with pure Rhizobium etli nodulation factors (NF), a unique type of signal molecule. The sequence analysis of samples from NF-induced and control libraries led to the identity of 132 mature miRNAs, including 63 novel miRNAs and 1984 phasiRNAs. From these, six miRNAs were significantly differentially expressed during NF induction, including one novel miRNA: miR RH82. A parallel degradome analysis of the same samples revealed 29 targets potentially cleaved by novel miRNAs specifically in NF-induced RH samples; however, these novel miRNAs were not differentially accumulated in this tissue. This study reveals Phaseolus vulgaris-specific novel miRNA candidates and their corresponding targets that meet all criteria to be involved in the regulation of the early nodulation events, thus setting the basis for exploring miRNA-mediated improvement of the common bean-rhizobia symbiosis. PMID- 27271619 TI - A Wireless Pressure Sensor Integrated with a Biodegradable Polymer Stent for Biomedical Applications. AB - This paper describes the fabrication and characterization of a wireless pressure sensor for smart stent applications. The micromachined pressure sensor has an area of 3.13 * 3.16 mm2 and is fabricated with a photosensitive SU-8 polymer. The wireless pressure sensor comprises a resonant circuit and can be used without the use of an internal power source. The capacitance variations caused by changes in the intravascular pressure shift the resonance frequency of the sensor. This change can be detected using an external antenna, thus enabling the measurement of the pressure changes inside a tube with a simple external circuit. The wireless pressure sensor is capable of measuring pressure from 0 mmHg to 230 mmHg, with a sensitivity of 0.043 MHz/mmHg. The biocompatibility of the pressure sensor was evaluated using cardiac cells isolated from neonatal rat ventricular myocytes. After inserting a metal stent integrated with the pressure sensor into a cardiovascular vessel of an animal, medical systems such as X-ray were employed to consistently monitor the condition of the blood vessel. No abnormality was found in the animal blood vessel for approximately one month. Furthermore, a biodegradable polymer (polycaprolactone) stent was fabricated with a 3D printer. The polymer stent exhibits better sensitivity degradation of the pressure sensor compared to the metal stent. PMID- 27271620 TI - A Novel Location-Centric IoT-Cloud Based On-Street Car Parking Violation Management System in Smart Cities. AB - Nowadays, in big cities, parking management is a critical issue from both the driver's side and the city government's side. From the driver's side, how to find an available parking lot in a city is a considerable concern. As a result, smart parking systems recently have received great interest, both in academia and industry. From the city government's side, how to manage and distribute such a limited public parking resource efficiently to give every visitor a fair chance of finding an on-street parking lot is also a considerable concern. However, existing studies of smart parking management focus only on assisting the driver's side to find available parking spaces. This study aims to raise a new perspective on such smart parking management and to propose a novel location-centric IoT cloud-based parking violation management system. The system is designed to assist authoritative officers in finding parking violations easily and recommends the least cost path for officers so that officers can achieve their highest productivity in finding parking violations and issuing parking tickets. Experimental results show that the system not only improves the productivity of officers in finding parking violations and issuing tickets, but also helps reduce the traveling cost of officers and to reduce the average violation period of violating cars considerably. PMID- 27271621 TI - A Synergy-Based Optimally Designed Sensing Glove for Functional Grasp Recognition. AB - Achieving accurate and reliable kinematic hand pose reconstructions represents a challenging task. The main reason for this is the complexity of hand biomechanics, where several degrees of freedom are distributed along a continuous deformable structure. Wearable sensing can represent a viable solution to tackle this issue, since it enables a more natural kinematic monitoring. However, the intrinsic accuracy (as well as the number of sensing elements) of wearable hand pose reconstruction (HPR) systems can be severely limited by ergonomics and cost considerations. In this paper, we combined the theoretical foundations of the optimal design of HPR devices based on hand synergy information, i.e., the inter joint covariation patterns, with textile goniometers based on knitted piezoresistive fabrics (KPF) technology, to develop, for the first time, an optimally-designed under-sensed glove for measuring hand kinematics. We used only five sensors optimally placed on the hand and completed hand pose reconstruction (described according to a kinematic model with 19 degrees of freedom) leveraging upon synergistic information. The reconstructions we obtained from five different subjects were used to implement an unsupervised method for the recognition of eight functional grasps, showing a high degree of accuracy and robustness. PMID- 27271622 TI - Integrated Toolset for WSN Application Planning, Development, Commissioning and Maintenance: The WSN-DPCM ARTEMIS-JU Project. AB - In this article we present the main results obtained in the ARTEMIS-JU WSN-DPCM project between October 2011 and September 2015. The first objective of the project was the development of an integrated toolset for Wireless sensor networks (WSN) application planning, development, commissioning and maintenance, which aims to support application domain experts, with limited WSN expertise, to efficiently develop WSN applications from planning to lifetime maintenance. The toolset is made of three main tools: one for planning, one for application development and simulation (which can include hardware nodes), and one for network commissioning and lifetime maintenance. The tools are integrated in a single platform which promotes software reuse by automatically selecting suitable library components for application synthesis and the abstraction of the underlying architecture through the use of a middleware layer. The second objective of the project was to test the effectiveness of the toolset for the development of two case studies in different domains, one for detecting the occupancy state of parking lots and one for monitoring air concentration of harmful gasses near an industrial site. PMID- 27271623 TI - Investigating the Impact of Possession-Way of a Smartphone on Action Recognition. AB - For the past few decades, action recognition has been attracting many researchers due to its wide use in a variety of applications. Especially with the increasing number of smartphone users, many studies have been conducted using sensors within a smartphone. However, a lot of these studies assume that the users carry the device in specific ways such as by hand, in a pocket, in a bag, etc. This paper investigates the impact of providing an action recognition system with the information of the possession-way of a smartphone, and vice versa. The experimental dataset consists of five possession-ways (hand, backpack, upper pocket, lower-pocket, and shoulder-bag) and two actions (walking and running) gathered by seven users separately. Various machine learning models including recurrent neural network architectures are employed to explore the relationship between the action recognition and the possession-way recognition. The experimental results show that the assumption of possession-ways of smartphones do affect the performance of action recognition, and vice versa. The results also reveal that a good performance is achieved when both actions and possession-ways are recognized simultaneously. PMID- 27271624 TI - An Optical Fiber Lateral Displacement Measurement Method and Experiments Based on Reflective Grating Panel. AB - An optical fiber sensing method based on a reflective grating panel is demonstrated for lateral displacement measurement. The reflective panel is a homemade grating with a periodic variation of its refractive index, which is used to modulate the reflected light intensity. The system structure and operation principle are illustrated in detail. The intensity calculation and simulation of the optical path are carried out to theoretically analyze the measurement performance. A distinctive fiber optic grating ruler with a special fiber optic measuring probe and reflective grating panel is set up. Experiments with different grating pitches are conducted, and long-distance measurements are executed to accomplish the functions of counting optical signals, subdivision, and discerning direction. Experimental results show that the proposed measurement method can be used to detect lateral displacement, especially for applications in working environments with high temperatures. PMID- 27271625 TI - Two Capacitive Micro-Machined Ultrasonic Transducers for Wind Speed Measurement. AB - This paper presents a new wind speed measurement method using a single capacitive micro-machined ultrasonic transducer (CMUT). The CMUT was arranged perpendicular to the direction of the wind flow, and a reflector was set up a short distance away, facing the CMUT. To reduce the size, weight, cost, and power consumption of conventional ultrasonic anemometers this study proposes two CMUT designs for the measurement of wind speed using either the amplitude of the signal or the time of flight (TOF). Each CMUT with a double array element design can transmit and receive signals in five different operation modes. Experiments showed that the two CMUT designs utilizing the TOF were better than those utilizing the amplitude of the signal for wind speed measurements ranging from 1 m/s to 10 m/s, providing a measurement error of less than 0.2 m/s. These results indicate that the sensitivity of the TOF is independent of the five operation modes. PMID- 27271626 TI - Segmentized Clear Channel Assessment for IEEE 802.15.4 Networks. AB - This paper proposed segmentized clear channel assessment (CCA) which increases the performance of IEEE 802.15.4 networks by improving carrier sense multiple access with collision avoidance (CSMA/CA). Improving CSMA/CA is important because the low-power consumption feature and throughput performance of IEEE 802.15.4 are greatly affected by CSMA/CA behavior. To improve the performance of CSMA/CA, this paper focused on increasing the chance to transmit a packet by assessing precise channel status. The previous method used in CCA, which is employed by CSMA/CA, assesses the channel by measuring the energy level of the channel. However, this method shows limited channel assessing behavior, which comes from simple threshold dependent channel busy evaluation. The proposed method solves this limited channel decision problem by dividing CCA into two groups. Two groups of CCA compare their energy levels to get precise channel status. To evaluate the performance of the segmentized CCA method, a Markov chain model has been developed. The validation of analytic results is confirmed by comparing them with simulation results. Additionally, simulation results show the proposed method is improving a maximum 8.76% of throughput and decreasing a maximum 3.9% of the average number of CCAs per packet transmission than the IEEE 802.15.4 CCA method. PMID- 27271627 TI - Street Viewer: An Autonomous Vision Based Traffic Tracking System. AB - The development of intelligent transportation systems requires the availability of both accurate traffic information in real time and a cost-effective solution. In this paper, we describe Street Viewer, a system capable of analyzing the traffic behavior in different scenarios from images taken with an off-the-shelf optical camera. Street Viewer operates in real time on embedded hardware architectures with limited computational resources. The system features a pipelined architecture that, on one side, allows one to exploit multi-threading intensively and, on the other side, allows one to improve the overall accuracy and robustness of the system, since each layer is aimed at refining for the following layers the information it receives as input. Another relevant feature of our approach is that it is self-adaptive. During an initial setup, the application runs in learning mode to build a model of the flow patterns in the observed area. Once the model is stable, the system switches to the on-line mode where the flow model is used to count vehicles traveling on each lane and to produce a traffic information summary. If changes in the flow model are detected, the system switches back autonomously to the learning mode. The accuracy and the robustness of the system are analyzed in the paper through experimental results obtained on several different scenarios and running the system for long periods of time. PMID- 27271628 TI - Power Performance Verification of a Wind Farm Using the Friedman's Test. AB - In this paper, a method of verification of the power performance of a wind farm is presented. This method is based on the Friedman's test, which is a nonparametric statistical inference technique, and it uses the information that is collected by the SCADA system from the sensors embedded in the wind turbines in order to carry out the power performance verification of a wind farm. Here, the guaranteed power curve of the wind turbines is used as one more wind turbine of the wind farm under assessment, and a multiple comparison method is used to investigate differences between pairs of wind turbines with respect to their power performance. The proposed method says whether the power performance of the specific wind farm under assessment differs significantly from what would be expected, and it also allows wind farm owners to know whether their wind farm has either a perfect power performance or an acceptable power performance. Finally, the power performance verification of an actual wind farm is carried out. The results of the application of the proposed method showed that the power performance of the specific wind farm under assessment was acceptable. PMID- 27271629 TI - A Novel Monopulse Angle Estimation Method for Wideband LFM Radars. AB - Traditional monopulse angle estimations are mainly based on phase comparison and amplitude comparison methods, which are commonly adopted in narrowband radars. In modern radar systems, wideband radars are becoming more and more important, while the angle estimation for wideband signals is little studied in previous works. As noise in wideband radars has larger bandwidth than narrowband radars, the challenge lies in the accumulation of energy from the high resolution range profile (HRRP) of monopulse. In wideband radars, linear frequency modulated (LFM) signals are frequently utilized. In this paper, we investigate the monopulse angle estimation problem for wideband LFM signals. To accumulate the energy of the received echo signals from different scatterers of a target, we propose utilizing a cross-correlation operation, which can achieve a good performance in low signal-to-noise ratio (SNR) conditions. In the proposed algorithm, the problem of angle estimation is converted to estimating the frequency of the cross correlation function (CCF). Experimental results demonstrate the similar performance of the proposed algorithm compared with the traditional amplitude comparison method. It means that the proposed method for angle estimation can be adopted. When adopting the proposed method, future radars may only need wideband signals for both tracking and imaging, which can greatly increase the data rate and strengthen the capability of anti-jamming. More importantly, the estimated angle will not become ambiguous under an arbitrary angle, which can significantly extend the estimated angle range in wideband radars. PMID- 27271630 TI - Experimental Identification of Smartphones Using Fingerprints of Built-In Micro Electro Mechanical Systems (MEMS). AB - The correct identification of smartphones has various applications in the field of security or the fight against counterfeiting. As the level of sophistication in counterfeit electronics increases, detection procedures must become more accurate but also not destructive for the smartphone under testing. Some components of the smartphone are more likely to reveal their authenticity even without a physical inspection, since they are characterized by hardware fingerprints detectable by simply examining the data they provide. This is the case of MEMS (Micro Electro-Mechanical Systems) components like accelerometers and gyroscopes, where tiny differences and imprecisions in the manufacturing process determine unique patterns in the data output. In this paper, we present the experimental evaluation of the identification of smartphones through their built-in MEMS components. In our study, three different phones of the same model are subject to repeatable movements (composing a repeatable scenario) using an high precision robotic arm. The measurements from MEMS for each repeatable scenario are collected and analyzed. The identification algorithm is based on the extraction of the statistical features of the collected data for each scenario. The features are used in a support vector machine (SVM) classifier to identify the smartphone. The results of the evaluation are presented for different combinations of features and Inertial Measurement Unit (IMU) outputs, which show that detection accuracy of higher than 90% is achievable. PMID- 27271631 TI - Flexible Piezoelectric Tactile Sensor Array for Dynamic Three-Axis Force Measurement. AB - A new flexible piezoelectric tactile sensor array based on polyvinylidene fluoride (PVDF) film is proposed for measuring three-axis dynamic contact force distribution. The array consists of six tactile units arranged as a 3 * 2 matrix with spacing 8 mm between neighbor units. In each unit, a PVDF film is sandwiched between four square-shaped upper electrodes and one square-shaped lower electrode, forming four piezoelectric capacitors. A truncated pyramid bump is located above the four piezoelectric capacitors to improve force transmission. A three-axis contact force transmitted from the top of the bump will lead to the four piezoelectric capacitors underneath undergoing different charge changes, from which the normal and shear components of the force can be calculated. A series of dynamic tests have been carried out by exerting sinusoidal forces with amplitudes ranging from 0 to 0.5 N in the x-axis, 0 to 0.5 N in the y-axis, and 0 to 1.5 N in the z-axis, separately. The tactile units show good sensitivities with 14.93, 14.92, and 6.62 pC/N in the x-, y-, and z-axes, respectively. They can work with good linearity, relatively low coupling effect, high repeatability, and acceptable frequency response in the range of 5-400 Hz to both normal and shear load. In addition, dynamic three-axis force measurement has been conducted for all of the tactile units. The average errors between the applied and calculated forces are 10.68% +/- 6.84%. Furthermore, the sensor array can be easily integrated onto a curved surface, such as robotic and prosthetic hands, due to its excellent flexibility. PMID- 27271632 TI - Abnormal Activity Detection Using Pyroelectric Infrared Sensors. AB - Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process. PMID- 27271633 TI - Point Cloud Based Relative Pose Estimation of a Satellite in Close Range. AB - Determination of the relative pose of satellites is essential in space rendezvous operations and on-orbit servicing missions. The key problems are the adoption of suitable sensor on board of a chaser and efficient techniques for pose estimation. This paper aims to estimate the pose of a target satellite in close range on the basis of its known model by using point cloud data generated by a flash LIDAR sensor. A novel model based pose estimation method is proposed; it includes a fast and reliable pose initial acquisition method based on global optimal searching by processing the dense point cloud data directly, and a pose tracking method based on Iterative Closest Point algorithm. Also, a simulation system is presented in this paper in order to evaluate the performance of the sensor and generate simulated sensor point cloud data. It also provides truth pose of the test target so that the pose estimation error can be quantified. To investigate the effectiveness of the proposed approach and achievable pose accuracy, numerical simulation experiments are performed; results demonstrate algorithm capability of operating with point cloud directly and large pose variations. Also, a field testing experiment is conducted and results show that the proposed method is effective. PMID- 27271634 TI - Stride Counting in Human Walking and Walking Distance Estimation Using Insole Sensors. AB - This paper proposes a novel method of estimating walking distance based on a precise counting of walking strides using insole sensors. We use an inertial triaxial accelerometer and eight pressure sensors installed in the insole of a shoe to record walkers' movement data. The data is then transmitted to a smartphone to filter out noise and determine stance and swing phases. Based on phase information, we count the number of strides traveled and estimate the movement distance. To evaluate the accuracy of the proposed method, we created two walking databases on seven healthy participants and tested the proposed method. The first database, which is called the short distance database, consists of collected data from all seven healthy subjects walking on a 16 m distance. The second one, named the long distance database, is constructed from walking data of three healthy subjects who have participated in the short database for an 89 m distance. The experimental results show that the proposed method performs walking distance estimation accurately with the mean error rates of 4.8% and 3.1% for the short and long distance databases, respectively. Moreover, the maximum difference of the swing phase determination with respect to time is 0.08 s and 0.06 s for starting and stopping points of swing phases, respectively. Therefore, the stride counting method provides a highly precise result when subjects walk. PMID- 27271635 TI - Pedestrian Detection at Day/Night Time with Visible and FIR Cameras: A Comparison. AB - Despite all the significant advances in pedestrian detection brought by computer vision for driving assistance, it is still a challenging problem. One reason is the extremely varying lighting conditions under which such a detector should operate, namely day and nighttime. Recent research has shown that the combination of visible and non-visible imaging modalities may increase detection accuracy, where the infrared spectrum plays a critical role. The goal of this paper is to assess the accuracy gain of different pedestrian models (holistic, part-based, patch-based) when training with images in the far infrared spectrum. Specifically, we want to compare detection accuracy on test images recorded at day and nighttime if trained (and tested) using (a) plain color images; (b) just infrared images; and (c) both of them. In order to obtain results for the last item, we propose an early fusion approach to combine features from both modalities. We base the evaluation on a new dataset that we have built for this purpose as well as on the publicly available KAIST multispectral dataset. PMID- 27271636 TI - Local Strategy Combined with a Wavelength Selection Method for Multivariate Calibration. AB - One of the essential factors influencing the prediction accuracy of multivariate calibration models is the quality of the calibration data. A local regression strategy, together with a wavelength selection approach, is proposed to build the multivariate calibration models based on partial least squares regression. The local algorithm is applied to create a calibration set of spectra similar to the spectrum of an unknown sample; the synthetic degree of grey relation coefficient is used to evaluate the similarity. A wavelength selection method based on simple to-use interactive self-modeling mixture analysis minimizes the influence of noisy variables, and the most informative variables of the most similar samples are selected to build the multivariate calibration model based on partial least squares regression. To validate the performance of the proposed method, ultraviolet-visible absorbance spectra of mixed solutions of food coloring analytes in a concentration range of 20-200 ug/mL is measured. Experimental results show that the proposed method can not only enhance the prediction accuracy of the calibration model, but also greatly reduce its complexity. PMID- 27271637 TI - Determination of Specific Losses in the Limbs of an Epstein Frame Using a Three Epstein Frame Methodology Applied to Grain Oriented Electrical Steels. AB - An experimental method to characterize the magnetic properties of Grain Oriented Electrical Steel in the rolling direction is proposed in this paper. It relies on the use of three 25 cm Epstein frames combined to generate three test-frames of different lengths. This enables the identification of the effective specific losses of the electrical steel when magnetization is applied along the rolling direction. As a consequence, it evidences the deviation of the loss figures obtained using the standardised Epstein test. The difference in losses is explained by the fact that the described method gives "only" the losses attached to the straight parts. The concept of the magnetic path length as defined by the standard is discussed. PMID- 27271638 TI - Accurate Vehicle Location System Using RFID, an Internet of Things Approach. AB - Modern infrastructure, such as dense urban areas and underground tunnels, can effectively block all GPS signals, which implies that effective position triangulation will not be achieved. The main problem that is addressed in this project is the design and implementation of an accurate vehicle location system using radio-frequency identification (RFID) technology in combination with GPS and the Global system for Mobile communication (GSM) technology, in order to provide a solution to the limitation discussed above. In essence, autonomous vehicle tracking will be facilitated with the use of RFID technology where GPS signals are non-existent. The design of the system and the results are reflected in this paper. An extensive literature study was done on the field known as the Internet of Things, as well as various topics that covered the integration of independent technology in order to address a specific challenge. The proposed system is then designed and implemented. An RFID transponder was successfully designed and a read range of approximately 31 cm was obtained in the low frequency communication range (125 kHz to 134 kHz). The proposed system was designed, implemented, and field tested and it was found that a vehicle could be accurately located and tracked. It is also found that the antenna size of both the RFID reader unit and RFID transponder plays a critical role in the maximum communication range that can be achieved. PMID- 27271639 TI - Identification of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Enzymatic Hydrolysates of Razor Clam Sinonovacula constricta. AB - Angiotensin I-converting enzyme (ACE) inhibitory activity of razor clam hydrolysates produced using five proteases, namely, pepsin, trypsin, alcalase, flavourzyme and proteases from Actinomucor elegans T3 was investigated. Flavourzyme hydrolysate showed the highest level of degree of hydrolysis (DH) (45.87%) followed by A. elegans T3 proteases hydrolysate (37.84%) and alcalase (30.55%). The A. elegans T3 proteases was observed to be more effective in generating small peptides with ACE-inhibitory activity. The 3 kDa membrane permeate of A. elegans T3 proteases hydrolysate showed the highest ACE-inhibitory activity with an IC50 of 0.79 mg/mL. After chromatographic separation by Sephadex G-15 gel filtration and reverse phase-high performance liquid chromatography, the potent fraction was subjected to MALDI/TOF-TOF MS/MS for identification. A novel ACE-inhibitory peptide (VQY) was identified exhibiting an IC50 of 9.8 MUM. The inhibitory kinetics investigation by Lineweaver-Burk plots demonstrated that the peptide acts as a competitive ACE inhibitor. The razor clam hydrolysate obtained by A. elegans T3 proteases could serve as a source of functional peptides with ACE-inhibitory activity for physiological benefits. PMID- 27271640 TI - Cembranoids from a Chinese Collection of the Soft Coral Lobophytum crassum. AB - Ten new cembrane-based diterpenes, locrassumins A-G (1-7), (-)-laevigatol B (8), (-)-isosarcophine (9), and (-)-7R,8S-dihydroxydeepoxysarcophytoxide (10), were isolated from a South China Sea collection of the soft coral Lobophytum crassum, together with eight known analogues (11-18). The structures of the new compounds were determined by extensive spectroscopic analysis and by comparison with previously reported data. Locrassumin C (3) possesses an unprecedented tetradecahydrobenzo[3,4]cyclobuta[1,2][8]annulene ring system. Compounds 1, 7, 12, 13, and 17 exhibited moderate inhibition against lipopolysaccharide (LPS) induced nitric oxide (NO) production with IC50 values of 8-24 MUM. PMID- 27271641 TI - Coral Carbonic Anhydrases: Regulation by Ocean Acidification. AB - Global change is a major threat to the oceans, as it implies temperature increase and acidification. Ocean acidification (OA) involving decreasing pH and changes in seawater carbonate chemistry challenges the capacity of corals to form their skeletons. Despite the large number of studies that have investigated how rates of calcification respond to ocean acidification scenarios, comparatively few studies tackle how ocean acidification impacts the physiological mechanisms that drive calcification itself. The aim of our paper was to determine how the carbonic anhydrases, which play a major role in calcification, are potentially regulated by ocean acidification. For this we measured the effect of pH on enzyme activity of two carbonic anhydrase isoforms that have been previously characterized in the scleractinian coral Stylophora pistillata. In addition we looked at gene expression of these enzymes in vivo. For both isoforms, our results show (1) a change in gene expression under OA (2) an effect of OA and temperature on carbonic anhydrase activity. We suggest that temperature increase could counterbalance the effect of OA on enzyme activity. Finally we point out that caution must, thus, be taken when interpreting transcriptomic data on carbonic anhydrases in ocean acidification and temperature stress experiments, as the effect of these stressors on the physiological function of CA will depend both on gene expression and enzyme activity. PMID- 27271642 TI - Empirical Model for Evaluating PM10 Concentration Caused by River Dust Episodes. AB - Around the estuary of the Zhuo-Shui River in Taiwan, the waters recede during the winter, causing an increase in bare land area and exposing a large amount of fine earth and sand particles that were deposited on the riverbed. Observations at the site revealed that when northeastern monsoons blow over bare land without vegetation or water cover, the fine particles are readily lifted by the wind, forming river dust, which greatly endangers the health of nearby residents. Therefore, determining which factors affect river dust and constructing a model to predict river dust concentration are extremely important in the research and development of a prototype warning system for areas at risk of river dust emissions. In this study, the region around the estuary of the Zhuo-Shui River (from the Zi-Qiang Bridge to the Xi-Bin Bridge) was selected as the research area. Data from a nearby air quality monitoring station were used to screen for days with river dust episodes. The relationships between PM10 concentration and meteorological factors or bare land area were analyzed at different temporal scales to explore the factors that affect river dust emissions. Study results showed that no single factor alone had adequate power to explain daily average or daily maximum PM10 concentration. Stepwise regression analysis of multiple factors showed that the model could not effectively predict daily average PM10 concentration, but daily maximum PM10 concentration could be predicted by a combination of wind velocity, temperature, and bare land area; the coefficient of determination for this model was 0.67. It was inferred that river dust episodes are caused by the combined effect of multiple factors. In addition, research data also showed a time lag effect between meteorological factors and hourly PM10 concentration. This characteristic was applied to the construction of a prediction model, and can be used in an early warning system for local residents. PMID- 27271643 TI - Development and Validation of an Instrument Measuring Theory-Based Determinants of Monitoring Obesogenic Behaviors of Pre-Schoolers among Hispanic Mothers. AB - Public health interventions are greatly needed for obesity prevention, and planning for such strategies should include community participation. The study's purpose was to develop and validate a theory-based instrument with low-income, Hispanic mothers of preschoolers, to assess theory-based determinants of maternal monitoring of child's consumption of fruits and vegetables and sugar-sweetened beverages (SSB). Nine focus groups with mothers were conducted to determine nutrition-related behaviors that mothers found as most obesogenic for their children. Next, behaviors were operationally defined and rated for importance and changeability. Two behaviors were selected for investigation (fruits and vegetable and SSB). Twenty semi-structured interviews with mothers were conducted next to develop culturally appropriate items for the instrument. Afterwards, face and content validity were established using a panel of six experts. Finally, the instrument was tested with a sample of 238 mothers. Psychometric properties evaluated included construct validity (using the maximum likelihood extraction method of factor analysis), and internal consistency reliability (Cronbach's alpha). Results suggested that all scales on the instrument were valid and reliable, except for the autonomy scales. Researchers and community planners working with Hispanic families can use this instrument to measure theory-based determinants of parenting behaviors related to preschoolers' consumption of fruits and vegetables, and SSB. PMID- 27271644 TI - A Diffusive Gradient-in-Thin-Film Technique for Evaluation of the Bioavailability of Cd in Soil Contaminated with Cd and Pb. AB - Management of heavy metal contamination requires accurate information about the distribution of bioavailable fractions, and about exchange between the solid and solution phases. In this study, we employed diffusive gradients in thin-films (DGT) and traditional chemical extraction methods (soil solution, HOAc, EDTA, CaCl2, and NaOAc) to determine the Cd bioavailability in Cd-contaminated soil with the addition of Pb. Two typical terrestrial species (wheat, Bainong AK58; maize, Zhengdan 958) were selected as the accumulation plants. The results showed that the added Pb may enhance the efficiency of Cd phytoextraction which is indicated by the increasing concentration of Cd accumulating in the plant tissues. The DGT-measured Cd concentrations and all the selected traditional extractants measured Cd concentrations all increased with increasing concentration of the addition Pb which were similar to the change trends of the accumulated Cd concentrations in plant tissues. Moreover, the Pearson regression coefficients between the different indicators obtained Cd concentrations and plants uptake Cd concentrations were further indicated significant correlations (p < 0.01). However, the values of Pearson regression coefficients showed the merits of DGT, CaCl2, and Csol over the other three methods. Consequently, the in situ measurement of DGT and the ex situ traditional methods could all reflect the inhibition effects between Cd and Pb. Due to the feature of dynamic measurements of DGT, it could be a robust tool to predict Cd bioavaiability in complex contaminated soil. PMID- 27271645 TI - Identifying Hot-Spots of Metal Contamination in Campus Dust of Xi'an, China. AB - The concentrations of heavy metals (As, Ba, Co, Cr, Cu, Mn, Ni, Pb, V, and Zn) in campus dust from kindergartens, elementary schools, middle schools, and universities in the city of Xi'an, China, were determined by X-ray fluorescence spectrometry. The pollution levels and hotspots of metals were analyzed using a geoaccumulation index and Local Moran's I, an indicator of spatial association, respectively. The dust samples from the campuses had metal concentrations higher than background levels, especially for Pb, Zn, Co, Cu, Cr, and Ba. The pollution assessment indicated that the campus dusts were not contaminated with As, Mn, Ni, or V, were moderately or not contaminated with Ba and Cr and were moderately to strongly contaminated with Co, Cu, Pb, and Zn. Local Moran's I analysis detected the locations of spatial clusters and outliers and indicated that the pollution with these 10 metals occurred in significant high-high spatial clusters, low high, or even high-low spatial outliers. As, Cu, Mn, Ni, Pb, V, and Zn had important high-high patterns in the center of Xi'an. The western and southwestern regions of the study area, i.e., areas of old and high-tech industries, have strongly contributed to the Co content in the campus dust. PMID- 27271646 TI - Individual Monitoring and Occupational Dose Record Management in China: History, Current Status and Perspectives. AB - This review paper presents an overview of individual monitoring, as well as the national dose register and dose record management of radiation workers in China. Progress has recently been made on the individual monitoring of radiation workers. A critical analysis of current status and problems in individual monitoring is also presented and necessary future research on individual monitoring, such as the monitoring technology in the form of the ring dosimeters and eye lens dosimeters, is suggested. PMID- 27271647 TI - Increased Risk of Respiratory Mortality Associated with the High-Tech Manufacturing Industry: A 26-Year Study. AB - Global high-tech manufacturers are mainly located in newly industrialized countries, raising concerns about adverse health consequences from industrial pollution for people living nearby. We investigated the ecological association between respiratory mortality and the development of Taiwan's high-tech manufacturing, taking into account industrialization and socioeconomic development, for 19 cities and counties-6 in the science park group and 13 in the control group-from 1982 to 2007. We applied a linear mixed-effects model to analyze how science park development over time is associated with age-adjusted and sex-specific mortality rates for asthma and chronic obstructive pulmonary disease (COPD). Asthma and female COPD mortality rates decreased in both groups, but they decreased 9%-16% slower in the science park group. Male COPD mortality rates increased in both groups, but the rate increased 10% faster in the science park group. Science park development over time was a significant predictor of death from asthma (p <= 0.0001) and COPD (p = 0.0212). The long-term development of clustered high-tech manufacturing may negatively affect nearby populations, constraining health advantages that were anticipated, given overall progress in living standards, knowledge, and health services. National governments should incorporate the long-term health effects on local populations into environmental impact assessments. PMID- 27271648 TI - Incidence and Mortality Risks of Cancer in Patients with Type 2 Diabetes: A Retrospective Study in Shanghai, China. AB - BACKGROUND: Evidence from epidemiologic investigation indicates that people with type 2 diabetes (T2DM) are at a significantly higher risk of many types of cancer and mortality. The aim of this study was to investigate the incidence and mortality risks of cancer in patients with T2DM compared with the general population in Shanghai, China. METHODS: Based on the Shanghai Diabetes Registry (SDR) database linking to the Shanghai Cancer Registry and Surveillance System (SCRSS), a total of 12,276 T2DM patients without cancer were defined and followed up from 1 December 2001 to 31 July 2011. Standardized incidence ratio (SIR) and standardized mortality ratio (SMR) with 95% confidence interval (CI) were calculated using the whole gender and age-matched general population of Shanghai as a reference during the same period. RESULTS: The overall cancer risk was found higher in both males and females T2DM patients, with the SIR of 3.14 (95% CI 2.73 3.56) and 4.29 (95% CI 3.64-4.94), respectively. The overall mortality risk of cancer also significantly increased with the SMR of 2.27 (95% CI 1.86-2.68) and 1.86 (95% CI 1.46-2.26), respectively. Pancreatic cancer was with the highest SIR and SMR in both genders. CONCLUSIONS: Compared with the general population, patients with T2DM were associated with higher incidence and mortality risks of cancer, especially pancreatic cancer. PMID- 27271649 TI - An Evaluation of Voluntary Varicella Vaccination Coverage in Zhejiang Province, East China. AB - BACKGROUND: In 2014 a 2-doses varicella vaccine (VarV) schedule was recommended by the Zhejiang Provincial Center for Disease Control and Prevention. We aimed to assess the coverage of the 1st dose of VarV (VarV1) and the 2nd dose of VarV (VarV2) among children aged 2-6 years through the Zhejiang Provincial Immunization Information System (ZJIIS) and to explore the determinants associated with the VarV coverage. METHODS: Children aged 2-6 years (born from 1 January 2009 to 31 December 2013) registered in ZJIIS were enrolled. Anonymized individual records of target children were extracted from the ZJIIS database on 1 January 2016, including their VarV and (measles-containing vaccine) MCV vaccination information. The VarV1 and VarV2 coverage rates were evaluated for each birth cohorts. The coverage of VarV also was estimated among strata defined by cities, gender and immigration status. We also evaluated the difference in coverage between VarV and MCV. RESULTS: A total of 3,028,222 children aged 2-6 years were enrolled. The coverage of VarV1 ranged from 84.8% to 87.9% in the 2009 2013 birth cohorts, while the coverage of VarV2 increased from 31.8% for the 2009 birth cohort to 48.7% for the 2011 birth cohort. Higher coverage rates for both VarV1 and VarV2 were observed among resident children in relevant birth cohorts. The coverage rates of VarV1 and VarV2 were lower than those for the 1st and 2nd dose of MCV, which were above 95%. The proportion of children who were vaccinated with VarV1 at the recommended age increased from 34.6% for the 2009 birth cohort to 75.2% for the 2013 birth cohort, while the proportion of children who were vaccinated with VarV2 at the recommended age increased from 19.7% for the 2009 birth cohort to 48.7% for the 2011 birth cohort. CONCLUSIONS: Our study showed a rapid increasing VarV2 coverage of children, indicating a growing acceptance of the 2-doses VarV schedule among children's caregivers and physicians after the new recommendation released. We highlighted the necessity for a 2-doses VarV vaccination school-entry requirement to achieve the high coverage of >90% and to eliminate disparities in coverage among sub-populations. We also recommended continuous monitoring of the VarV coverage via ZJIIS over time. PMID- 27271650 TI - Genetic Variation in POU4F3 and GRHL2 Associated with Noise-Induced Hearing Loss in Chinese Population: A Case-Control Study. AB - Noise-induced hearing loss (NIHL) is an important occupational disease worldwide resulting from interactions between genetic and environmental factors. The purpose of this study was to examine whether genetic variations in POU4F3 and GRHL2 may influence susceptibility to NIHL in the Chinese population. A matched case-control study was carried out among 293 hearing loss individuals and 293 normal hearing workers drawn from a population of 3790 noise-exposed workers. Ten single-nucleotide polymorphisms (SNPs) in POU4F3 and GRHL2 were selected and genotyped. Logistic regression was performed to analyze the main effects of SNPs and the interactions between noise exposure and SNPs. Moreover, the interactions between predictor haplotypes and noise exposure were also analyzed. Analysis revealed that the CC genotype of rs1981361 in the GRHL2 gene was associated with a higher risk of NIHL (adjusted OR = 1.59; 95% CI: 1.08-2.32, p = 0.018). Additionally, the GG genotype of rs3735715 in the GRHL2 gene was also a risk genotype (adjusted OR = 1.48; 95% CI: 1.01-2.19, p = 0.046). Significant interactions were found between rs3735715, rs1981361 (GRHL2), rs1368402 as well as rs891969 (POU4F3) and noise exposure in the high-level exposure groups. Furthermore, the protective haplotype CA in the POU4F3 gene and the risk haplotype GCCG in the GRHL2 gene were identified combined with noise exposure. These results indicated that GRHL2 might be an NIHL susceptibility gene, but the effect of POU4F3 on NIHL could only be detected when taking noise exposure into account, and their effects were enhanced by higher levels of noise exposure. However, the differences were not significant after the Bonferroni correction was applied. These results should be seen as suggestive. PMID- 27271652 TI - Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method. AB - Health-care waste (HCW) management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM) issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS) for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS) can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively. PMID- 27271651 TI - Hand- and Object-Mouthing of Rural Bangladeshi Children 3-18 Months Old. AB - Children are exposed to environmental contaminants by placing contaminated hands or objects in their mouths. We quantified hand- and object-mouthing frequencies of Bangladeshi children and determined if they differ from those of U.S. children to evaluate the appropriateness of applying U.S. exposure models in other socio cultural contexts. We conducted a five-hour structured observation of the mouthing behaviors of 148 rural Bangladeshi children aged 3-18 months. We modeled mouthing frequencies using 2-parameter Weibull distributions to compare the modeled medians with those of U.S. children. In Bangladesh the median frequency of hand-mouthing was 37.3 contacts/h for children 3-6 months old, 34.4 contacts/h for children 6-12 months old, and 29.7 contacts/h for children 12-18 months old. The median frequency of object-mouthing was 23.1 contacts/h for children 3-6 months old, 29.6 contacts/h for children 6-12 months old, and 15.2 contacts/h for children 12-18 months old. At all ages both hand- and object-mouthing frequencies were higher than those of U.S. children. Mouthing frequencies were not associated with child location (indoor/outdoor). Using hand- and object-mouthing exposure models from U.S. and other high-income countries might not accurately estimate children's exposure to environmental contaminants via mouthing in low- and middle income countries. PMID- 27271653 TI - A Tale of Two RNAs during Viral Infection: How Viruses Antagonize mRNAs and Small Non-Coding RNAs in The Host Cell. AB - Viral infection initiates an array of changes in host gene expression. Many viruses dampen host protein expression and attempt to evade the host anti-viral defense machinery. Host gene expression is suppressed at several stages of host messenger RNA (mRNA) formation including selective degradation of translationally competent messenger RNAs. Besides mRNAs, host cells also express a variety of noncoding RNAs, including small RNAs, that may also be subject to inhibition upon viral infection. In this review we focused on different ways viruses antagonize coding and noncoding RNAs in the host cell to its advantage. PMID- 27271655 TI - Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin. AB - Influenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We and others have combined high-throughput mutagenesis with deep sequencing to estimate the effects of large numbers of mutations to influenza genes. However, these measurements have suffered from substantial experimental noise due to a variety of technical problems, the most prominent of which is bottlenecking during the generation of mutant viruses from plasmids. Here we describe advances that ameliorate these problems, enabling us to measure with greatly improved accuracy and reproducibility the effects of all amino-acid mutations to an H1 influenza hemagglutinin on viral replication in cell culture. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm at much higher resolution the results of previous studies suggesting that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. We also show that other regions of hemagglutinin-including the stalk epitopes targeted by broadly neutralizing antibodies-have a much lower inherent capacity to tolerate point mutations. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution. PMID- 27271656 TI - Malignant Mesothelioma and Delivery of Polyphenols. AB - Malignant Mesothelioma (MM) is a rare form of cancer that affects the thin cell wall lining of the body's internal organs and structures.[...]. PMID- 27271657 TI - Effect of Immune-Enhancing Enteral Nutrition Enriched with or without Beta-Glucan on Immunomodulation in Critically Ill Patients. AB - We investigated whether high-protein enteral nutrition with immune-modulating nutrients (IMHP) enriched with beta-glucan stimulates immune function in critically ill patients. In a randomized double-blind placebo-controlled study, 30 patients consumed one of three types of enteral nutrition: a control or IMHP with and without beta-glucan. The IMHP with beta-glucan group showed increases in natural killer (NK) cell activities relative to the baseline, and greater increases were observed in NK cell activities relative to the control group after adjusting for age and gender. The IMHP groups with and without beta-glucan had greater increases in serum prealbumin and decreases in high-sensitivity C reactive protein (hs-CRP) than the control group. The control group had a greater decrease in peripheral blood mononuclear cell (PBMC) interleukin (IL)-12 production than the IMHP with and without beta-glucan groups. In all patients, the change (Delta) in hs-CRP was correlated with Delta prealbumin and Delta PBMC IL-12, which were correlated with DeltaNK cell activity and Delta prealbumin. This study showed beneficial effects of a combination treatment of beta-glucan and IMHP on NK cell activity. Additionally, strong correlations among changes in NK cell activity, PBMC IL-12, and hs-CRP suggested that beta-glucan could be an attractive candidate for stimulating protective immunity without enhanced inflammation (ClinicalTrials.gov: NCT02569203). PMID- 27271654 TI - The Role of microRNAs in the Pathogenesis of Herpesvirus Infection. AB - MicroRNAs (miRNAs) are small non-coding RNAs important in gene regulation. They are able to regulate mRNA translation through base-pair complementarity. Cellular miRNAs have been involved in the regulation of nearly all cellular pathways, and their deregulation has been associated with several diseases such as cancer. Given the importance of microRNAs to cell homeostasis, it is no surprise that viruses have evolved to take advantage of this cellular pathway. Viruses have been reported to be able to encode and express functional viral microRNAs that target both viral and cellular transcripts. Moreover, viral inhibition of key proteins from the microRNA pathway and important changes in cellular microRNA pool have been reported upon viral infection. In addition, viruses have developed multiple mechanisms to avoid being targeted by cellular microRNAs. This complex interaction between host and viruses to control the microRNA pathway usually favors viral infection and persistence by either reducing immune detection, avoiding apoptosis, promoting cell growth, or promoting lytic or latent infection. One of the best examples of this virus-host-microRNA interplay emanates from members of the Herperviridae family, namely the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2), human cytomegalovirus (HCMV), human herpesvirus 8 (HHV-8), and the Epstein-Barr virus (EBV). In this review, we will focus on the general functions of microRNAs and the interactions between herpesviruses, human hosts, and microRNAs and will delve into the related mechanisms that contribute to infection and pathogenesis. PMID- 27271658 TI - Comparison of Intradialytic Parenteral Nutrition with Glucose or Amino Acid Mixtures in Maintenance Hemodialysis Patients. AB - Many long-term maintenance hemodialysis patients have symptoms of protein-energy wasting caused by malnutrition. Each session of hemodialysis removes about 10 to 12 g of amino acids and 200 to 480 kcal of energy. Patients receiving hemodialysis for chronic kidney disease may be undernourished for energy, protein consumption, or both. Non-diabetic hemodialysis patients were randomized to three treatment groups: oral supplementation, oral supplementation plus high concentration glucose solution (250 mL containing 50% glucose) and these two interventions plus 8.5% amino acids solution. The post-treatment energy status of the glucose group was significantly higher than its baseline level, whereas the control group's status was significantly lower. The glucose group had significantly higher concentrations of asparagine, glutamine, glycine, alanine, and lysine after treatment. All treatment groups had significantly increased hemoglobin levels but significantly decreased transferrin levels after treatment compared to baseline. After treatment, the amino acid group had significantly higher albumin level compared to the glucose group (p = 0.001) and significantly higher prealbumin level compared to the control group (p = 0.017). In conclusion, long-term intervention with high-concentration glucose solution at each hemodialysis session is a simple and cheap method that replenished energy stores lost during hemodialysis of non-diabetic patients. PMID- 27271659 TI - The Distribution of Obesity Phenotypes in HIV-Infected African Population. AB - The distribution of body size phenotypes in people with human immunodeficiency virus (HIV) infection has yet to be characterized. We assessed the distribution of body size phenotypes overall, and according to antiretroviral therapy (ART), diagnosed duration of the infection and CD4 count in a sample of HIV infected people recruited across primary care facilities in the Western Cape Province, South Africa. Adults aged >= 18 years were consecutively recruited using random sampling procedures, and their cardio-metabolic profile were assessed during March 2014 and February 2015. They were classified across body mass index (BMI) categories as normal-weight (BMI < 25 kg/m2), overweight (25 <= BMI < 30 kg/m2), and obese (BMI >= 30 kg/m2), and further classified according to their metabolic status as "metabolically healthy" vs. "metabolically abnormal" if they had less than two vs. two or more of the following abnormalities: high blood glucose, raised blood pressure, raised triglycerides, and low HDL-cholesterol. Their cross classification gave the following six phenotypes: normal-weight metabolically healthy (NWMH), normal-weight metabolically abnormal (NWMA), overweight metabolically healthy (OvMH), overweight metabolically abnormal (OvMA), obese metabolically healthy (OMH), and obese metabolically abnormal (OMA). Among the 748 participants included (median age 38 years (25th-75th percentiles: 32-44)), 79% were women. The median diagnosed duration of HIV was five years; the median CD4 count was 392 cells/mm3 and most participants were on ART. The overall distribution of body size phenotypes was the following: 31.7% (NWMH), 11.7% (NWMA), 13.4% (OvMH), 9.5% (OvMA), 18.6% (OMH), and 15.1% (OMA). The distribution of metabolic phenotypes across BMI levels did not differ significantly in men vs. women (p = 0.062), in participants below vs. those at or above median diagnosed duration of HIV infection (p = 0.897), in participants below vs. those at or above median CD4 count (p = 0.447), and by ART regimens (p = 0.205). In this relatively young sample of HIV-infected individuals, metabolically abnormal phenotypes are frequent across BMI categories. This highlights the importance of general measures targeting an overall improvement in cardiometabolic risk profile across the spectrum of BMI distribution in all adults with HIV. PMID- 27271662 TI - On the Importance of Processing Conditions for the Nutritional Characteristics of Homogenized Composite Meals Intended for Infants. AB - The nutritional quality of infant food is an important consideration in the effort to prevent a further increase in the rate of childhood obesity. We hypothesized that the canning of composite infant meals would lead to elevated contents of carboxymethyl-lysine (CML) and favor high glycemic and insulinemic responses compared with milder heat treatment conditions. We have compared composite infant pasta Bolognese meals that were either conventionally canned (CANPBol), or prepared by microwave cooking (MWPBol). A meal where the pasta and Bolognese sauce were separate during microwave cooking (MWP_CANBol) was also included. The infant meals were tested at breakfast in healthy adults using white wheat bread (WWB) as reference. A standardized lunch meal was served at 240 min and blood was collected from fasting to 360 min after breakfast. The 2-h glucose response (iAUC) was lower following the test meals than with WWB. The insulin response was lower after the MWP_CANBol (-47%, p = 0.0000) but markedly higher after CANPBol (+40%, p = 0.0019), compared with WWB. A combined measure of the glucose and insulin responses (ISIcomposite) revealed that MWP_CANBol resulted in 94% better insulin sensitivity than CANPBol. Additionally, the separate processing of the meal components in MWP_CANBol resulted in 39% lower CML levels than the CANPBol. It was therefore concluded that intake of commercially canned composite infant meals leads to reduced postprandial insulin sensitivity and increased exposure to oxidative stress promoting agents. PMID- 27271660 TI - Biomarkers of Aging: From Function to Molecular Biology. AB - Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products. PMID- 27271661 TI - Effects of Whey, Caseinate, or Milk Protein Ingestion on Muscle Protein Synthesis after Exercise. AB - Whey protein (WP) is characterized as a "fast" protein and caseinate (CA) as a "slow" protein according to their digestion and absorption rates. We hypothesized that co-ingestion of milk proteins (WP and CA) may be effective for prolonging the muscle protein synthesis response compared to either protein alone. We therefore compared the effect of ingesting milk protein (MP) to either WP or CA alone on muscle protein synthesis after exercise in rats. We also compared the effects of these milk-derived proteins to a control, soy protein (SP). Male Sprague-Dawley rats swam for two hours. Immediately after exercise, one of the following four solutions was administered: WP, CA, MP, or SP. Individual rats were euthanized at designated postprandial time points and triceps muscle samples collected for measurement of the protein fractional synthesis rate (FSR). FSR tended to increase in all groups post-ingestion, although the initial peaks of FSR occurred at different times (WP, peak time = 60 min, FSR = 7.76%/day; MP, peak time = 90 min, FSR = 8.34%/day; CA, peak time = 120 min, FSR = 7.85%/day). Milk-derived proteins caused significantly greater increases (p < 0.05) in FSR compared with SP at different times (WP, 60 min; MP, 90 and 120 min; CA, 120 min). Although statistical analysis could not be performed, the calculated the area under the curve (AUC) values for FSR following this trend were: MP, 534.61; CA, 498.22; WP, 473.46; and SP, 406.18. We conclude that ingestion of MP, CA or WP causes the initial peak time in muscle protein synthesis to occur at different times (WP, fast; MP, intermediate; CA, slow) and the dairy proteins have a superior effect on muscle protein synthesis after exercise compared with SP. PMID- 27271663 TI - Marginal Ascorbate Status (Hypovitaminosis C) Results in an Attenuated Response to Vitamin C Supplementation. AB - Inadequate dietary intake of vitamin C results in hypovitaminosis C, defined as a plasma ascorbate concentration <=23 MUmol/L. Our objective was to carry out a retrospective analysis of two vitamin C supplementation studies to determine whether supplementation with 50 mg/day vitamin C is sufficient to restore adequate ascorbate status (>=50 MUmol/L) in individuals with hypovitaminosis C. Plasma ascorbate data from 70 young adult males, supplemented with 50 or 200 mg/day vitamin C for up to six weeks, was analyzed. Hypovitaminosis C status was identified based on plasma ascorbate being <=23 MUmol/L and the response of these individuals to vitamin C supplementation was examined. Of the participants consuming 50 mg/day vitamin C for up to six weeks, those with hypovitaminosis C at baseline achieved plasma concentrations of only ~30 MUmol/L, whereas the remainder reached ~50 MUmol/L. Participants who consumed 200 mg/day vitamin C typically reached saturating concentrations (>65 MUmol/L) within one week, while those with hypovitaminosis C required two weeks to reach saturation. Regression modelling indicated that the participants' initial ascorbate status and body weight explained ~30% of the variability in the final ascorbate concentration. Overall, our analysis revealed that supplementation with 50 mg/day vitamin C, which resulted in a total dietary vitamin C intake of 75 mg/day, was insufficient to achieve adequate plasma ascorbate concentrations in individuals with hypovitaminosis C. Furthermore, increased body weight had a negative impact on ascorbate status. PMID- 27271664 TI - The Effects of an Olive Fruit Polyphenol-Enriched Yogurt on Body Composition, Blood Redox Status, Physiological and Metabolic Parameters and Yogurt Microflora. AB - In the present study we investigated the effects of an olive polyphenol-enriched yogurt on yogurt microflora, as well as hematological, physiological and metabolic parameters, blood redox status and body composition. In a randomized double-blind, crossover design, 16 (6 men, 10 women) nonsmoking volunteers with non-declared pathology consumed either 400 g of olive fruit polyphenol-enriched yogurt with 50 mg of encapsulated olive polyphenols (experimental condition-EC) or 400 g of plain yogurt (control condition-CC) every day for two weeks. Physiological measurements and blood collection were performed before and after two weeks of each condition. The results showed that body weight, body mass index, hip circumference and systolic blood pressure decreased significantly (p < 0.05) following the two-week consumption of yogurt regardless of condition. A tendency towards significance for decreased levels of low density lipoprotein (LDL) cholesterol (p = 0.06) and thiobarbituric acid reactive substances (p < 0.05) following two weeks of polyphenol-enriched yogurt consumption was observed. The population of lactic acid bacteria (LAB) and production of lactate in yogurt were significantly enhanced after addition of olive polyphenols, contrary to the population of yeasts and molds. The results indicate that consumption of the polyphenol-enriched yogurt may help individuals with non-declared pathology reduce body weight, blood pressure, LDL cholesterol levels and lipid peroxidation, and promote growth of beneficial LAB. PMID- 27271665 TI - Vitamin D in Fibromyalgia: A Causative or Confounding Biological Interplay? AB - Fibromyalgia (FM) is a chronic syndrome with an increasing prevalence, characterized by widespread musculoskeletal pain in combination with a variety of cognitive symptoms and fatigue. A plethora of scientific evidence that has accumulated during the last decades, resulted in a significant improvement of the understanding of the pathophysiology of the disease. However, current therapeutic approaches in patients with FM remains a multidimensional approach including patient education, behavioral therapy, exercise, pain management, and relief of chronic symptoms, rather than the use drug therapies, based on the mechanisms of disease development. Vitamin D, a fat-soluble vitamin derived mainly from skin synthesis through ultraviolet radiation, has been recognized to manifest a plethora of extraskeletal actions, apart from its fundamental role in skeletal and calcium homeostasis, including modulation of cell growth, neuromuscular actions, and potential anti-inflammatory properties. Recent findings indicate that hypovitaminosis D to be highly prevalent in patients with FM. Supplementation studies are limited so far, indicating potential beneficial effects on pain and severity of the disease, however specific recommendations are lacking. This review aims to summarize and critically appraise data regarding the pathophysiological interplay between vitamin D and FM, available results from observational and supplementation studies so far, with a clinical discourse on current knowledge gaps and future research agenda. PMID- 27271666 TI - Nutrition in Pregnancy: Optimising Maternal Diet and Fetal Adaptations to Altered Nutrient Supply. PMID- 27271667 TI - A Systematic Investigation into the Environmental Fate of Microcystins and The Potential Risk: Study in Lake Taihu. AB - A systematic investigation was conducted in Lake Taihu in autumn of 2013 and 2014, in order to understand the environmental fate of microcystins (MCs) and evaluate the health risk from MCs. Samples of water, algal cells, macrophytes, shrimps and fish were taken to detect MCs by HPLC-MS/MS after solid phase extraction. Widespread MC contamination in water, algal cells, macrophytes, shrimps and fish was found in Lake Taihu. The ubiquitous presence of MCs in water, algal cells and biota was found in 100% of samples. MC accumulation was in the order of primary producer > tertiary consumer > secondary consumer > primary consumer. The highest levels of MCs in macrophytes, shrimps and fish tissue were found in Potamogeton maackianus, Exopalaemon modestus, and Hyporhamphus intermedius, respectively. The MCs level in shrimps and the tissues of three fish species, Neosalanx tangkahkeii taihuensis, Coilia ectenes and silver carp, was closely linked to their dietary exposure. Ceratophyllum demersum L. was an ideal plant for introduction into lakes to protect against Microcystis blooms and MCs, due to its ability to absorb nutrients, accumulate large amounts of MCs and tolerate these toxins compared to other macrophytes. The average daily intakes (ADIs) of MCs for Exopalaemon modestus and three fish species, Coilia ectenes, Hyporhamphus intermedius and Carassius carassius, were all above the tolerable daily intakes (TDI) set by the World Health Organization (WHO), implying there existed potential threats to human health. PMID- 27271668 TI - Effects of Zinc Chelators on Aflatoxin Production in Aspergillus parasiticus. AB - Zinc concentrations strongly influence aflatoxin accumulation in laboratory media and in food and feed crops. The presence of zinc stimulates aflatoxin production, and the absence of zinc impedes toxin production. Initial studies that suggested a link between zinc and aflatoxin biosynthesis were presented in the 1970s. In the present study, we utilized two zinc chelators, N,N,N',N'-tetrakis (2 pyridylmethyl) ethane-1,2-diamine (TPEN) and 2,3-dimercapto-1-propanesulfonic acid (DMPS) to explore the effect of zinc limitation on aflatoxin synthesis in Aspergillus parasiticus. TPEN but not DMPS decreased aflatoxin biosynthesis up to six-fold depending on whether A. parasiticus was grown on rich or minimal medium. Although we observed significant inhibition of aflatoxin production by TPEN, no detectable changes were observed in expression levels of the aflatoxin pathway gene ver-1 and the zinc binuclear cluster transcription factor, AflR. Treatment of growing A. parasiticus solid culture with a fluorescent zinc probe demonstrated an increase in intracellular zinc levels assessed by increases in fluorescent intensity of cultures treated with TPEN compared to controls. These data suggest that TPEN binds to cytoplasmic zinc therefore limiting fungal access to zinc. To investigate the efficacy of TPEN on food and feed crops, we found that TPEN effectively decreases aflatoxin accumulation on peanut medium but not in a sunflower seeds-derived medium. From an application perspective, these data provide the basis for biological differences that exist in the efficacy of different zinc chelators in various food and feed crops frequently contaminated by aflatoxin. PMID- 27271670 TI - AAU-Specific RNA Cleavage Mediated by MazF Toxin Endoribonuclease Conserved in Nitrosomonas europaea. AB - Nitrosomonas europaea carries numerous toxin-antitoxin systems. However, despite the abundant representation in its chromosome, studies have not surveyed the underlying molecular functions in detail, and their biological roles remain enigmatic. In the present study, we found that a chromosomally-encoded MazF family member, predicted at the locus NE1181, is a functional toxin endoribonuclease, and constitutes a toxin-antitoxin system, together with its cognate antitoxin, MazE. Massive parallel sequencing provided strong evidence that this toxin endoribonuclease exhibits RNA cleavage activity, primarily against the AAU triplet. This sequence-specificity was supported by the results of fluorometric assays. Our results indicate that N. europaea alters the translation profile and regulates its growth using the MazF family of endoribonuclease under certain stressful conditions. PMID- 27271671 TI - A Multi-Step miRNA-mRNA Regulatory Network Construction Approach Identifies Gene Signatures Associated with Endometrioid Endometrial Carcinoma. AB - We aimed to identify endometrioid endometrial carcinoma (EEC)-related gene signatures using a multi-step miRNA-mRNA regulatory network construction approach. Pathway analysis showed that 61 genes were enriched on many carcinoma related pathways. Among the 14 highest scoring gene signatures, six genes had been previously shown to be endometrial carcinoma. By qRT-PCR and next generation sequencing, we found that a gene signature (CPEB1) was significantly down regulated in EEC tissues, which may be caused by hsa-miR-183-5p up-regulation. In addition, our literature surveys suggested that CPEB1 may play an important role in EEC pathogenesis by regulating the EMT/p53 pathway. The miRNA-mRNA network is worthy of further investigation with respect to the regulatory mechanisms of miRNAs in EEC. CPEB1 appeared to be a tumor suppressor in EEC. Our results provided valuable guidance for the functional study at the cellular level, as well as the EEC mouse models. PMID- 27271673 TI - Contrasting Foraging Patterns: Testing Resource-Concentration and Dilution Effects with Pollinators and Seed Predators. AB - Resource concentration effects occur when high resource density patches attract and support more foragers than low density patches. In contrast, resource dilution effects can occur if high density patches support fewer consumers. In this study, we examined the foraging rates of pollinators and seed predators on two perennial plant species (Rudbeckia triloba and Verbena stricta) as functions of resource density. Specifically, we examined whether resource-dense patches (densities of flower and seeds on individual plants) resulted in greater visitation and seed removal rates, respectively. We also examined whether foraging rates were context-dependent by conducting the study in two sites that varied in resource densities. For pollinators, we found negative relationships between the density of flowers per plant and visitation rates, suggesting dilution effects. For seed predators, we found positive relationships consistent with concentration effects. Saturation effects and differences in foraging behaviors might explain the opposite relationships; most of the seed predators were ants (recruitment-based foragers), and pollinators were mostly solitary foragers. We also found that foraging rates were site-dependent, possibly due to site-level differences in resource abundance and consumer densities. These results suggest that these two plant species may benefit from producing as many flowers as possible, given high levels of pollination and low seed predation. PMID- 27271672 TI - Field Method for Testing Repellency of an Icaridin-Containing Skin Lotion against Vespid Wasps. AB - Vespid wasps are ecologically beneficial predators of insects but their stings also pose a human health risk. Current control methods based on killing vespids are suboptimal. Here, the repellent effect against Vespula vulgaris of a 20% icaridin skin lotion was evaluated under field conditions. An experimental setup was designed in which six artificial skin pieces (10 * 10 cm) were video-recorded for 1 h, to count each min the numbers of flying and feeding vespids. Prior to monitoring, five pieces were successively smeared with 2 mg of cream per cm2, in 30 min intervals, from t = -120 min to 0. The sixth sheet remained untreated to serve as a control. One milliliter of an attractant, fruit jam, was deposited on each of the six surfaces at t = 0. The control surface was free of any flying or feeding vespid during an average period of 25 min, whereas the other five surfaces (treated at t = -120, -90, -60, -30, and 0 min) remained vespid-free for 39, 40, 45, 49, and 51 min, respectively. The skin lotion remained significantly active for at least 2 h. The experimental methodology is adjustable and allows the study of repellents against vespids in semi-natural conditions. PMID- 27271674 TI - Physiological Effects of Ergot Alkaloid and Indole-Diterpene Consumption on Sheep under Hot and Thermoneutral Ambient Temperature Conditions. AB - A controlled feeding study was undertaken to determine the physiological and production effects of consuming perennial ryegrass alkaloids (fed via seed) under extreme heat in sheep. Twenty-four Merino ewe weaners (6 months; initial BW 30.8 +/- 1.0 kg) were selected and the treatment period lasted 21 days following a 14 day acclimatisation period. Two levels of two factors were used. The first factor was alkaloid, fed at a nil (NilAlk) or moderate level (Alk; 80 MUg/kg LW ergovaline and 20.5 MUg/kg.LW lolitrem B). The second factor was ambient temperature applied at two levels; thermoneutral (TN; constant 21-22 degrees C) or heat (Heat; 9:00 AM-5:00 PM at 38 degrees C; 5:00 PM-9:00 AM at 21-22 degrees C), resulting in four treatments, NilAlk TN, NilAlk Heat, Alk TN and Alk Heat. Alkaloid consumption reduced dry matter intake ( p = 0.008), and tended to reduce liveweight ( p = 0.07). Rectal temperature and respiration rate were increased by both alkaloid and heat ( p < 0.05 for all). Respiration rate increased to severe levels when alkaloid and heat were combined, indicating the short term effects which may be occurring in perennial ryegrass toxicosis (PRGT) areas during severe weather conditions, a novel finding. When alkaloid ingestion and heat were administered separately, similar physiological responses occurred, indicating alkaloid ingestion causes a similar heat stress response to 38 degrees C heat. PMID- 27271669 TI - An Overview of Helicobacter pylori VacA Toxin Biology. AB - The VacA toxin secreted by Helicobacter pylori enhances the ability of the bacteria to colonize the stomach and contributes to the pathogenesis of gastric adenocarcinoma and peptic ulcer disease. The amino acid sequence and structure of VacA are unrelated to corresponding features of other known bacterial toxins. VacA is classified as a pore-forming toxin, and many of its effects on host cells are attributed to formation of channels in intracellular sites. The most extensively studied VacA activity is its capacity to stimulate vacuole formation, but the toxin has many additional effects on host cells. Multiple cell types are susceptible to VacA, including gastric epithelial cells, parietal cells, T cells, and other types of immune cells. This review focuses on the wide range of VacA actions that are detectable in vitro, as well as actions of VacA in vivo that are relevant for H. pylori colonization of the stomach and development of gastric disease. PMID- 27271675 TI - Characterization of Tensile Mechanical Behavior of MSCs/PLCL Hybrid Layered Sheet. AB - A layered construct was developed by combining a porous polymer sheet and a cell sheet as a tissue engineered vascular patch. The primary objective of this study is to investigate the influence of mesenchymal stem cells (MSCs) sheet on the tensile mechanical properties of porous poly-(l-lactide-co-epsilon-caprolactone) (PLCL) sheet. The porous PLCL sheet was fabricated by the solid-liquid phase separation method and the following freeze-drying method. The MSCs sheet, prepared by the temperature-responsive dish, was then layered on the top of the PLCL sheet and cultured for 2 weeks. During the in vitro study, cellular properties such as cell infiltration, spreading and proliferation were evaluated. Tensile test of the layered construct was performed periodically to characterize the tensile mechanical behavior. The tensile properties were then correlated with the cellular properties to understand the effect of MSCs sheet on the variation of the mechanical behavior during the in vitro study. It was found that MSCs from the cell sheet were able to migrate into the PLCL sheet and actively proliferated into the porous structure then formed a new layer of MSCs on the opposite surface of the PLCL sheet. Mechanical evaluation revealed that the PLCL sheet with MSCs showed enhancement of tensile strength and strain energy density at the first week of culture which is characterized as the effect of MSCs proliferation and its infiltration into the porous structure of the PLCL sheet. New technique was presented to develop tissue engineered patch by combining MSCs sheet and porous PLCL sheet, and it is expected that the layered patch may prolong biomechanical stability when implanted in vivo. PMID- 27271677 TI - Abiotic Deposition of Fe Complexes onto Leptothrix Sheaths. AB - Bacteria classified in species of the genus Leptothrix produce extracellular, microtubular, Fe-encrusted sheaths. The encrustation has been previously linked to bacterial Fe oxidases, which oxidize Fe(II) to Fe(III) and/or active groups of bacterial exopolymers within sheaths to attract and bind aqueous-phase inorganics. When L. cholodnii SP-6 cells were cultured in media amended with high Fe(II) concentrations, Fe(III) precipitates visibly formed immediately after addition of Fe(II) to the medium, suggesting prompt abiotic oxidation of Fe(II) to Fe(III). Intriguingly, these precipitates were deposited onto the sheath surface of bacterial cells as the population was actively growing. When Fe(III) was added to the medium, similar precipitates formed in the medium first and were abiotically deposited onto the sheath surfaces. The precipitates in the Fe(II) medium were composed of assemblies of globular, amorphous particles (ca. 50 nm diameter), while those in the Fe(III) medium were composed of large, aggregated particles (>=3 um diameter) with a similar amorphous structure. These precipitates also adhered to cell-free sheaths. We thus concluded that direct abiotic deposition of Fe complexes onto the sheath surface occurs independently of cellular activity in liquid media containing Fe salts, although it remains unclear how this deposition is associated with the previously proposed mechanisms (oxidation enzyme- and/or active group of organic components-involved) of Fe encrustation of the Leptothrix sheaths. PMID- 27271678 TI - Aspergillus Biofilms in Human Disease. AB - The biofilm phenotype of Aspergillus species is an important and accepted clinical entity. While industrially these biofilms have been used extensively in important biofermentations, their role in clinical infection is less well defined. A recent flurry of activity has demonstrated that these interesting filamentous moulds have the capacity to form biofilms both in vitro and in vivo, and through various investigations have shown that these are exquisitely resistant to antifungal therapies through a range of adaptive resistance mechanisms independent of defined genetic changes. This review will explore the clinical importance of these biofilms and provide contemporary information with respect to their clinical management. PMID- 27271676 TI - Chloramphenicol Derivatives as Antibacterial and Anticancer Agents: Historic Problems and Current Solutions. AB - Chloramphenicol (CAM) is the D-threo isomer of a small molecule, consisting of a p-nitrobenzene ring connected to a dichloroacetyl tail through a 2-amino-1,3 propanediol moiety. CAM displays a broad-spectrum bacteriostatic activity by specifically inhibiting the bacterial protein synthesis. In certain but important cases, it also exhibits bactericidal activity, namely against the three most common causes of meningitis, Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Resistance to CAM has been frequently reported and ascribed to a variety of mechanisms. However, the most important concerns that limit its clinical utility relate to side effects such as neurotoxicity and hematologic disorders. In this review, we present previous and current efforts to synthesize CAM derivatives with improved pharmacological properties. In addition, we highlight potentially broader roles of these derivatives in investigating the plasticity of the ribosomal catalytic center, the main target of CAM. PMID- 27271679 TI - Disinfectants to Fight Oral Candida Biofilms. AB - Oral biofilms, especially those caused by oral mycobiota, which include Candida species, are very difficult to eradicate, due to their complex structure and recalcitrance. Moreover, the mouth is prone to be colonized since it presents different types of surfaces, especially biomaterials and dental implants, often associated with a high rate of infections. Therefore, although disinfection of the oral cavity is of major importance, the number of commercially available disinfectants is not high. However, new solutions, as silver nanoparticles are being developed to help oral biofilms' eradication. PMID- 27271680 TI - The Extracellular Matrix of Fungal Biofilms. AB - A key feature of biofilms is their production of an extracellular matrix. This material covers the biofilm cells, providing a protective barrier to the surrounding environment. During an infection setting, this can include such offenses as host cells and products of the immune system as well as drugs used for treatment. Studies over the past two decades have revealed the matrix from different biofilm species to be as diverse as the microbes themselves. This chapter will review the composition and roles of matrix from fungal biofilms, with primary focus on Candida species, Saccharomyces cerevisiae, Aspergillus fumigatus, and Cryptococcus neoformans. Additional coverage will be provided on the antifungal resistance proffered by the Candida albicans matrix, which has been studied in the most depth. A brief section on the matrix produced by bacterial biofilms will be provided for comparison. Current tools for studying the matrix will also be discussed, as well as suggestions for areas of future study in this field. PMID- 27271681 TI - Candida albicans in Multispecies Oral Communities; A Keystone Commensal? AB - The complexity of the oral cavity, in which many hundreds of microbial species interact represents a challenge for modern microbiologists. What are all these species doing there? And why do we accept so many opportunistic pathogens to be part of our health (commensal) microflora? While the role of bacteria are often being studied, the role of fungi in the interactions within the oral cavity are understudied. This is partly because fungi in the oral cavity are generally considered as pathogens and related to diseases. In this chapter we will explore mechanisms of interaction between bacteria and fungi in the oral cavity that are involved in maintenance of oral health. We will argue that fungi in general and C. albicans specifically, should be regarded a keystone commensal in the oral cavity. PMID- 27271682 TI - Quantifying over-estimation in early stopped clinical trials and the "freezing effect" on subsequent research. AB - BACKGROUND: Despite the wide use of the design with statistical stopping guidelines to stop a randomized clinical trial early for efficacy, there are unsettled debates of potential harmful consequences of such designs. These concerns include the possible over-estimation of treatment effects in early stopped trials and a newer argument of a "freezing effect" that will halt future randomized clinical trials on the same comparison since an early stopped trial represents an effective declaration that randomization to the unfavored arm is unethical. The purpose of this study is to determine the degree of bias in designs that allow for early stopping and to assess the impact on estimation if indeed future experimentation is "frozen" by an early stopped trial. METHODS: We perform simulations to study the effect of early stopping. We simulate a collection of trials and contrast the treatment-effect estimates (risk differences and ratios) with the simulation truth. Simulations consider various scenarios of between-study variation, including an empirically derived distribution of effects from the clinical literature. RESULTS: Across the trials whose true effects are sampled from a uniform distribution, estimates from trials that stop early for efficacy deviate minimally from the simulation truth (median bias of the estimate of risk difference is 0.005). Over-estimation becomes appreciable only when the true effect is close to the null value 0 (median bias of the risk difference estimate is 0.04) or when stopping happens with 40% information or less; however, stopping under these situations is rare. We also find slight reverse bias of the estimated treatment effect (median bias of the risk difference estimate is -0.002) among trials that do not cross the early stopping boundaries but continue to the final analysis. Similar results occur with relative risk estimates. In contrast, Bayesian estimation of the treatment effect shrinks the estimate from trials stopping early and pulls back under estimation from completed trials, largely rectifying any over-estimation among trials that terminate early. Regarding the so-called freezing effect, the pooled effects from meta-analyses that include truncated randomized clinical trials show an unimportant deviation from the true value, even when no subsequent trials are conducted after a truncated randomized clinical trial. CONCLUSION: Group sequential designs with stopping rules seek to minimize exposure of patients to a disfavored therapy and speed dissemination of results, and such designs do not lead to materially biased estimates. The likelihood and magnitude of a "freezing effect" is minimal. Superiority demonstrated in a randomized clinical trial stopping early and designed with appropriate statistical stopping rules is likely a valid inference, even if the estimate may be slightly inflated. PMID- 27271683 TI - Fidelity to a behavioral intervention to improve goals of care decisions for nursing home residents with advanced dementia. AB - BACKGROUND/AIMS: Ensuring fidelity to a behavioral intervention implemented in nursing homes requires awareness of the unique considerations of this setting for research. The purpose of this article is to describe the goals of care cluster randomized trial and the methods used to monitor and promote fidelity to a goals of care decision aid intervention delivered in nursing homes. METHODS: The cluster randomized trial tested whether a decision aid for goals of care in advanced dementia could improve (1) the quality of communication and decision making, (2) the quality of palliative care, and (3) the quality of dying for nursing home residents with advanced dementia. In 11 intervention nursing homes, family decision-makers for residents with advanced dementia received a two component intervention: viewing a video decision aid about goals of care choices and then participating in a structured decision-making discussion with the nursing home care plan team, ideally within 3 months after the decision aid was viewed. Following guidelines from the National Institutes of Health Behavior Change Consortium, fidelity was assessed in study design, in nursing home staff training for intervention implementation, and in monitoring and receipt of the intervention. We also monitored the content and timing of goals of care discussions. RESULTS: Investigators enrolled 151 family decision-maker/resident dyads in intervention sites; of those, 136 (90%) received both components of the intervention, and 92%-99% of discussions addressed each of four recommended content areas-health status, goals of care, choice of a goal, and treatment planning. A total of 94 (69%) of the discussions between family decision-makers and the nursing home care team were completed within 3 months. CONCLUSION: The methods we used for intervention fidelity allowed nursing home staff to implement a goals of care decision aid intervention for advanced dementia. Key supports for implementation included design features that aligned with nursing home practice, efficient staff training, and a structured guide for goals of care discussions between family decision-makers and staff. These approaches may be used to promote fidelity to behavioral interventions in future clinical trials. PMID- 27271684 TI - Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1. AB - One of the main hallmarks of Alzheimer's disease includes the neurofibrillary tangles formation produced by hyperphosphorylation of the Tau protein, whose expression is putatively regulated by the ovarian hormones estradiol and progesterone. Hippocampus is a brain region that participates in many functions related to learning and memory; in addition, it is abundant in both estradiol and progesterone receptors. In this study, we explore the expression of Tau hyperphosphorylation at hippocampus and the performance of rats in an autoshaping learning task at 5, 10 and 15 months after the ovaries removal. In these animals, ovariectomy was performed at 3 months of age. These data were compared with those derived from intact rats at 8, 13 and 18 months old. A clear decrease in the number of conditioned responses of both intact and ovariectomized rats in the autoshaping learning task was observed. The interaction of both factors confirms that, in this test, learning varies depending on aging and the presence or absence of ovaries. A progressive increase in hippocampal Tau phosphorylation at Ser-396 was observed in either intact or ovariectomized rats. Interestingly, an interaction between the analyzed factors shows that such hyperphosphorylation was potentiated by the absence of ovaries. These results emphasize the importance of aging and the lack of ovarian hormones for an associative learning test and for the expression of one of the most important hallmarks of Alzheimer's disease. PMID- 27271685 TI - Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer. AB - Expansion of the polyglutamine (polyQ) track of the Huntingtin (HTT) protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD). Although there is general agreement that HTT toxicity resides primarily in N terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS) to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the reaction profile in the context of emerging cellular distress. The data provide some new candidates for the toxic species and some new reservations about more well-established candidates. Compared to other known markers of HTT toxicity, nuclear DNA damage appears to be a relatively early pathological event. PMID- 27271686 TI - Next-generation precision genome engineering and plant biotechnology. PMID- 27271687 TI - Dose-dependent effects of higher methionine levels on the transcriptome and metabolome of transgenic Arabidopsis seeds. AB - KEY MESSAGE: Higher methionine levels in transgenic Arabidopsis seeds trigger the accumulation of stress-related transcripts and primary metabolites. These responses depend on the levels of methionine within seeds. Methionine, a sulfur containing amino acid, is a key metabolite in plant cells. To reveal the regulatory role of the Arabidopsis thaliana CYSTATHIONINE gamma-SYNTHASE (AtCGS), methionine main regulatory enzyme, in the synthesis of methionine in seeds, we generated transgenic RNAi seeds with targeted repression of AtCGS during late developmental stages of seeds. Unexpectedly, these seeds accumulated 2.5-fold more methionine than wild-type seeds. To study the nature of these seeds, transcriptomic and primary metabolite profiling were employed using Affymetrix ATH1 microarray and gas chromatography-mass spectrometry analyses, respectively. The results were compared to transgenic Arabidopsis seeds expressing a feedback insensitive form of AtCGS (named SSE-AtD-CGS) that were previously showed to accumulate up to sixfold more soluble methionine than wild-type seeds. Statistical assessments showed that the nature of transcriptomic and metabolic changes that occurred in RNAi::AtCGS seeds were relatively similar, but to lesser extents, to those previously reported for SSE-AtD-CGS seeds, and linked to the induction of global transcriptomic and metabolic responses associated with stronger desiccation stress. As transgenic seeds obtained by both manipulations exhibited higher, but different methionine levels, the data strongly suggest that these changes depend on the absolute amounts of methionine within seeds and much less to the expression level of AtCGS. PMID- 27271688 TI - Postmeiotic development of pollen surface layers requires two Arabidopsis ABCG type transporters. AB - KEY MESSAGE: Two Arabidopsis ABC transporters, ABCG1 and ABCG16, are expressed in the tapetal layer, specifically after postmeiotic microspore release, and play important roles in pollen surface development. The male gametophytic cells of terrestrial plants, the pollen grains, travel far before fertilization, and thus require strong protective layers, which take the form of a pollen coat and a pollen wall. The protective surface structures are generated by the tapetum, the tissue surrounding the developing gametophytes. Many ABC transporters, including Arabidopsis thaliana ABCG1 and ABCG16, have been shown to play essential roles in the development of such protective layers. However, the details of the mechanism of their function remain to be clarified. In this study, we show that ABCG1 and ABCG16 are localized at the plasma membrane of tapetal cells, specifically after postmeiotic microspore release, and play critical roles in the postmeiotic stages of male gametophyte development. Consistent with this stage-specific expression, the abcg1 abcg16 double knockout mutant exhibited defects in pollen development after postmeiotic microspore release; their microspores lacked intact nexine and intine layers, exhibited defects in pollen mitosis I, displayed ectopic deposits of arabinogalactan proteins, failed to complete cytokinesis, and lacked sperm cells. Interestingly, the double mutant exhibited abnormalities in the internal structures of tapetal cells, too; the storage organelles of tapetal cells, tapetosomes and elaioplasts, were morphologically altered. Thus, this work reveals that the lack of ABCG1 and ABCG16 at the tapetal cell membrane causes a broad range of defects in pollen, as well as in tapetal cells themselves. Furthermore, these results suggest that normal pollen surface development is necessary for normal development of the pollen cytoplasm. PMID- 27271689 TI - Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model. AB - OBJECTIVES: Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ induced lung damage in a rat experimental model. METHODS: Female Sprague-Dawley rats (n = 24) were allocated into three groups: sham, PQ and PQ + 3 aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15 mg/kg PQ intraperitoneally in PQ and PQ + 3 AB groups. 3-AB (10 mg/kg twice per day) was administered to the PQ + 3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis. RESULTS: Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-beta) levels and histological injury scores in the PQ + 3-AB group were significantly lower than in the PQ group (P < 0.05, PQ vs. PQ + 3-AB). Total antioxidant capacity in the PQ + 3-AB group was significantly higher than in the PQ group (P < 0.05, PQ + 3-AB vs. PQ). CONCLUSION: Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity. PMID- 27271690 TI - Exogenous orienting of attention in hearing: a virtual reality paradigm to assess auditory attention in neglect patients. AB - While mechanisms of orienting attention in unilateral spatial neglect (USN) have frequently been studied in the visual domain, these mechanisms remain relatively unexplored in the auditory domain. Our first goal was to replicate Spence and Driver's (J Exp Psychol Hum 22:1005-1030, 1994) results with a virtual reality paradigm. This paradigm simulated a 3-dimensional auditory space with headphones. Our second aim was to study auditory profiles of orienting attention in USN. In a first experiment, 18 healthy participants performed an auditory cueing spatial paradigm (either a target-detection task or a target-lateralization task). In a second experiment, 14 right-stroke patients (10 with USN and 4 without USN) performed these two same tasks. As in Spence and Driver's (J Exp Psychol Hum 22:1005-1030, 1994), our first experiment showed that spatial representations are not utilized for the detection of auditory stimuli. However, during the lateralization task, participants were quicker to detect targets preceded by a spatially congruent cue, which suggests that our paradigm could be suitable for studying orienting attention in hearing. Our second experiment found that patients with USN also needed an explicit spatial task to be sensitive to auditory spatial cueing. In the target-lateralization task, they showed effects lateralized only to one side of space, whereas patients without USN did not. Although our paradigm needs replications to better understand orienting attention impairments in hearing in USN, this study could have implications for the development of clinical tasks that could assess auditory spatial attention in USN syndrome. PMID- 27271691 TI - [Not Available]. PMID- 27271692 TI - [Not Available]. PMID- 27271693 TI - [Not Available]. PMID- 27271695 TI - Metabolite amyloids: a new paradigm for inborn error of metabolism disorders. AB - The formation of ordered amyloid assemblies is associated with major human degenerative disorders, including Alzheimer's disease, Parkinson's disease, and type 2 diabetes. Amyloid fibrils are elongated nanoscale structures that bind to specific dyes (including thioflavin T and Congo red). Amyloid fibrillar assemblies or their early intermediates are known to induce apoptotic cytotoxic effect. Until recently, amyloid fiber formation was observed only with proteins and peptides. We reported in 2012 that a single amino acid, phenylalanine, could also form typical amyloid fibrils with the same morphology, dye-binding specificity, and electron diffraction pattern as protein amyloids. X-ray crystallography demonstrated the formation of supramolecular beta-sheet-like organization by phenylalanine at its zwitterionic form. Metabolite amyloids had pronounced cytotoxicity that could be depleted by treatment with antibodies raised against the phenylalanine structures. We suggested that the observed amyloid formation could explain some of the symptoms observed in phenylketonuria (PKU) upon the accumulation of phenylalanine. Follow-up studies by other groups revealed the ability of phenylalanine amyloids to bind to membranes, as observed with protein amyloids. Furthermore, the doxycycline amyloid formation inhibitor was shown to also affect the formation of phenylalanine amyloids. In 2015, it was reported that other metabolites involved in metabolic disorders, including adenine, uracil, tyrosine, and orotic acid, could form amyloid-like assemblies. It was further demonstrated that the assemblies induce apoptotic cell death. Taken together, we suggest a new hypothesis to understand the etiology of degenerative processes observed in inborn error of metabolism disorders and indicate new avenues for treatment. PMID- 27271694 TI - Riboflavin transport and metabolism in humans. AB - Recent studies elucidated how riboflavin transporters and FAD forming enzymes work in humans and create a coordinated flavin network ensuring the maintenance of cellular flavoproteome. Alteration of this network may be causative of severe metabolic disorders such as multiple acyl-CoA dehydrogenase deficiency (MADD) or Brown-Vialetto-van Laere syndrome. A crucial step in the maintenance of FAD homeostasis is riboflavin uptake by plasma and mitochondrial membranes. Therefore, studies on recently identified human plasma membrane riboflavin transporters are presented, together with those in which still unidentified mitochondrial riboflavin transporter(s) have been described. A main goal of future research is to fill the gaps still existing as for some transcriptional, functional and structural details of human FAD synthases (FADS) encoded by FLAD1 gene, a novel "redox sensing" enzyme. In the frame of the hypothesis that FADS, acting as a "FAD chaperone", could play a crucial role in the biogenesis of mitochondrial flavo-proteome, several basic functional aspects of flavin cofactor delivery to cognate apo-flavoenzyme are also briefly dealt with. The establishment of model organisms performing altered FAD homeostasis will improve the molecular description of human pathologies. The molecular and functional studies of transporters and enzymes herereported, provide guidelines for improving therapies which may have beneficial effects on the altered metabolism. PMID- 27271696 TI - Tyrosinemia type I and not treatment with NTBC causes slower learning and altered behavior in mice. AB - Tyrosinemia type I is a recessive inborn error of metabolism caused by mutations in the fumarylacetoacetate hydrolase (FAH) gene, coding for the final enzyme in the metabolism of tyrosine. This renders FAH nonfunctional and without treatment, toxic metabolites accumulate causing liver and kidney damage. Introduction of the drug NTBC in 2002 offered a treatment which inhibits an upstream enzyme, preventing the production of the toxic metabolites. There is now a long-term survival rate of greater than 90 % in children, but there are reports of lower cognitive function and IQ as well as schooling and behavioral problems in these children. We studied a mouse model of tyrosinemia type I to gain insight into the effects of tyrosinemia type I and treatment with NTBC on mouse learning, memory, and behavior. In the Barnes maze, visual and spatial cues can be used by mice to remember the location of a dark escape box. The primary time, distance, and strategy taken by the mice to locate the escape box is a measure of learning and memory. Our findings show that mice with tyrosinemia type I were slower to learn than wild-type mice treated with NTBC and made more mistakes, but were capable of learning and storing long-term memory. After learning the location of the target hole, mice with tyrosinemia type I respond differently to a change in location and were less flexible in learning the new target hole location. Our findings suggest that this slower learning and cognitive difference is caused by tyrosinemia type I and not by the treatment with NTBC. PMID- 27271697 TI - Optimal Timing for Venous Systemic Oxygen Persufflation Supplemented with Nitric Oxide Gas in Cold-Stored, Warm Ischemia-Damaged Experimental Liver Grafts. AB - BACKGROUND/AIM: Worldwide shortage of donor organs has increased the use of donation after cardiac death (DCD). The aim of this study was to analyze the best time point for venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the 1st and 24th hour of cold storage (CS) in warm ischemia (WI)-damaged experimental liver grafts. MATERIALS AND METHODS: Liver grafts (n = 5) were retrieved after 30 min of WI induced by cardiac arrest and CS in histidine-tryptophan-ketoglutarate solution at 4 degrees C. The 1st hour group was immediately persufflated with a VSOP plus NO (VSOP+NO) mixture for 1 h followed by 23 h of static CS (DCD+NO 1st hour). The 24th hour group entailed CS for 23 h followed by 1 h of VSOP+NO persufflation (DCD+NO 24th hour). CS livers without WI but with VSOP served as controls. CS livers with WI represented the fourth group (DCD). Viability of the liver grafts was assessed by normothermic isolated reperfusion for 45 min with oxygenated Krebs-Henseleit buffer. RESULTS: Data are presented as mean +/- SEM (control vs. DCD vs. DCD+NO 1st hour vs. DCD+NO 24th hour). After 45 min of reperfusion, the DCD+NO 1st hour group showed significantly lower aspartate aminotransferase (13.4 +/- 5.3, 63.2 +/- 17.3, 25.6 +/- 3.9, and 82.8 +/- 27.3 U/l) and lactate dehydrogenase levels (289.4 +/- 41.2, 2,139.4 +/- 542.7, 577.2 +/- 117.2, and 2,429 +/- 221.6 U/l). Malondialdehyde levels were significantly abrogated (1.0 +/- 0.3, 2.7 +/- 1, 1.0 +/- 0, and 3.9 +/- 1.2 nmol/ml). Significantly higher levels of portal venous pressure were recorded in the DCD+NO 24th hour group (12.0 +/- 1, 21.2 +/- 3.1, 16.1 +/- 1, and 23.2 +/- 3.5 mm Hg). NO levels were recorded after 5 min of reperfusion (1.42 +/- 0.17, 1.8 +/- 0.2, 2.7 +/- 0.2, and 2.6 +/- 0.1 MUmol/l). Bile production levels showed no statistical significance (23.2 +/- 3.8, 27.3 +/- 1.8, 43.5 +/- 18, and 31 +/- 2.5 MUl/45 min). CONCLUSION: Our results present the beneficial effects of NO combined with VSOP during the 1st hour of CS of WI-damaged experimental liver grafts. PMID- 27271698 TI - Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data. AB - The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies. PMID- 27271699 TI - Patient-reported outcomes and surgical triage: A gap in patient-centered care? AB - PURPOSE: To help address wait times for elective surgery, British Columbia has implemented a triaging system that assigns priority levels to patients based on their diagnoses. The extent to which these priority levels concords with patients' assessment of their health status is not known. The purpose of this study was to measure the association between the priority levels assigned to patients and their patient-reported outcomes data collected at the time of being enrolled on the surgical wait list. METHODS: Patients waiting for elective surgery in the Vancouver Coastal Health Authority were sampled. Participants completed a set of generic and condition-specific patient-reported outcome instruments, including: the EQ-5D(3L) (general health), PEG (pain), and the PHQ-9 (depression). A multivariate ordered logistic model was used to regress patient reported outcome values on the priority level assigned at the time of wait list registration. RESULTS: A total of 2725 participants completed the survey package (response rate 49 %). Using the EQ-5D(3L), 63 % reported having problems with pain or discomfort, 41 % problems performing usual activities, 36 % problems with depression or anxiety, 28 % problems with mobility, and 8 % a problem with self care. The results from the ordered logistic model indicated very little association between the patient-reported outcomes and wait list priority levels, when adjusted for patient factors. CONCLUSIONS: This study observed no relationship between patients' self-reported health status and their assigned priority level for elective surgery. A more patient-centered approach to triaging patients for surgical treatment would incorporate patients' perspective in surgical wait list prioritization systems. PMID- 27271700 TI - Thrombin generation assay in untreated whole human blood. AB - Present coagulation assays fail to detect mild coagulation disorders, while thrombin-generation (TG) assays solve this problem. However, most of them only work with threated blood samples, which makes them labor intensive, time consuming, unreliable, and expensive. We have developed a TG electrophoretic assay that uses a thrombin specific charge-changing fluorescent peptide substrate, electrophoretic separation, and requires a drop of blood. The limit of detection of the assay was 1.97 nM in phosphate buffer saline and 6.82 nM in citrated whole blood. The assay was used to determine the TG in whole blood from healthy volunteers (n = 6, one aspirin user), over 30 min, after the blood was drawn; the TG increased from a baseline level of 2 * 10(6) RFU to 1.2 * 10(13) RFU. The lag time between the blood draw and initial burst of TG was 6 min for the volunteers (n = 5) and 15 min for the aspirin user. Specificity of the assay was evaluated by reacting our substrate with the heparinized blood samples and other proteases. The TG electrophoretic assay was designed and tested in the whole human blood, requiring no sample preparation, 5 MUL of blood, 45 min, and it detected differences in coagulation patterns between a volunteer taking aspirin and non-aspirin users. PMID- 27271701 TI - Association between primary Sjogren's syndrome and pregnancy complications: a systematic review and meta-analysis. AB - Systemic autoimmune disorders may interfere with normal reproductive function resulting in negative outcome of pregnancy. Primary Sjogren's syndrome (pSS) is a common rheumatic disease that mostly affects females. There are many reports that this condition may increase risk of pregnancy complications and fetal loss. However, data regarding these adverse outcomes are scarce and inconclusive. We performed a systematic review and meta-analysis of available articles that assess the association between pSS and adverse pregnancy outcome. We comprehensively searched the databases of MEDLINE and EMBASE from their dates of inception to March 2016 and reviewed papers with validity criteria. A random-effects model was used to evaluate pregnancy complications in patients with pSS and healthy controls. From 20 full-text articles, 7 studies involving 544 patients and 1586 pregnancies were included in the meta-analysis. Fetal complications included spontaneous abortion, stillbirth, neonatal deaths, and intrauterine growth retardation. Compared with healthy pregnancy, patients with pSS had significantly higher chance of neonatal deaths (pooled odds ratio (OR) = 1.77, 95 % confidence interval (CI) 1.28 to 1.46, p = 0.01). However, there were no significant associations between pSS and premature birth (OR = 2.10, 95 % CI 0.59-7.46, p = 0.25), spontaneous abortion (OR = 1.46, 95 % CI 0.72-2.93, p = 0.29), artificial abortion (OR = 1.12, 95 % CI 0.52-2.61, p = 0.71), or stillbirth (OR = 1.05, 95 % CI 0.38-2.97, p = 0.92). There is an increased risk of fetal loss in pregnant patients with pSS. The presented evidence further supports multidisciplinary care for these patients to prevent complications during pregnancy. PMID- 27271702 TI - A combination of liver fluke infection and traditional northeastern Thai foods associated with cholangiocarcinoma development. AB - Opisthorchis viverrini infection is one of the risk factors for cholangiocarcinoma (CCA) in northeast Thailand, a region with one of the highest reported incidence rates of CCA. The traditional practice of eating raw fish, repeated exposure to liver flukes, and consumption of nitrosamine-contaminated food are major risk factors for CCA. So far, there have been no reports about which northeastern traditional dishes may be involved in CCA development. The present study, thus, investigated the effects of traditional foods. It focused specifically on the consumption of fermented foods in combination with O. viverrini infection in hamsters. Syrian hamsters were divided into six groups: (i) normal hamsters, (ii) O. viverrini infection only and (iii)-(vi) O. viverrini infection plus fermented foods (pla som-fish fermented for 1 day), som wua fermented beef, som phag-fermented vegetables, and pla ra-fish fermented for 6 months. Syrian hamster livers were used for analysis of histopathological changes through hematoxylin and eosin; Sirius Red; and immunohistostaining for cytokeratin-19, proliferating cell nuclear antigen, and CA19-9. Hamster sera were used for liver and kidney function tests. Results of all O. viverrini-infected groups and fermented food groups showed that histopathological changes consisted primarily of aggregations of inflammatory cells surrounding the hepatic bile duct, especially at the hilar region. However, there was a difference in virulence. Interestingly, aggregations of inflammatory cells, new bile duct formation, and fibrosis were observed in subcapsular hepatic tissue, which correlated to positive immunohistochemical staining and increased liver function test. The present study suggests that fermented food consumption can exacerbate cholangitis and cholangiofibrosis, which are risk factors for cholangiocarcinoma associated opisthorchiasis. PMID- 27271704 TI - Multiplex Assay for Simultaneous Detection of Mycoplasma genitalium and Macrolide Resistance Using PlexZyme and PlexPrime Technology. AB - Mycoplasma genitalium is a cause of non-gonoccocal urethritis (NGU) in men and cervicitis and pelvic inflammatory disease in women. Recent international data also indicated that the first line treatment, 1 gram stat azithromycin therapy, for M. genitalium is becoming less effective, with the corresponding emergence of macrolide resistant strains. Increasing failure rates of azithromycin for M. genitalium has significant implications for the presumptive treatment of NGU and international clinical treatment guidelines. Assays able to predict macrolide resistance along with detection of M. genitalium will be useful to enable appropriate selection of antimicrobials to which the organism is susceptible and facilitate high levels of rapid cure. One such assay recently developed is the MG 23S assay, which employs novel PlexZymeTM and PlexPrimeTM technology. It is a multiplex assay for detection of M. genitalium and 5 mutations associated with macrolide resistance. The assay was evaluated in 400 samples from 254 (186 males and 68 females) consecutively infected participants, undergoing tests of cure. Using the MG 23S assay, 83% (331/440) of samples were positive, with 56% of positives carrying a macrolide resistance mutation. Comparison of the MG 23S assay to a reference qPCR method for M. genitalium detection and high resolution melt analysis (HRMA) and sequencing for detection of macrolide resistance mutations, resulted in a sensitivity and specificity for M. genitalium detection and for macrolide resistance of 99.1/98.5% and 97.4/100%, respectively. The MG 23S assay provides a considerable advantage in clinical settings through combined diagnosis and detection of macrolide resistance. PMID- 27271707 TI - Core Concept: Quantum dots. PMID- 27271705 TI - Family Communication in Inherited Cardiovascular Conditions in Ireland. AB - Over 100,000 individuals living in Ireland carry a mutated gene for an inherited cardiac condition (ICC), most of which demonstrate an autosomal dominant pattern of inheritance. First-degree relatives of individuals with these mutations are at a 50 % risk of being a carrier: disclosing genetic information to family members can be complex. This study explored how families living in Ireland communicate genetic information about ICCs and looked at the challenges of communicating information, factors that may affect communication and what influence this had on family relationships. Face to face interviews were conducted with nine participants using an approved topic guide and results analysed using thematic analysis. The participants disclosed that responsibility to future generations, gender, proximity and lack of contact all played a role in family communication. The media was cited as a source of information about genetic information and knowledge of genetic information tended to have a positive effect on families. Results from this study indicate that individuals are willing to inform family members, particularly when there are children and grandchildren at risk, and different strategies are utilised. Furthermore, understanding of genetics is partially regulated not only by their families, but by the way society handles information. Therefore, genetic health professionals should take into account the familial influence on individuals and their decision to attend genetic services, and also that of the media. PMID- 27271709 TI - Diarrhea in Critically Ill Patients: The Role of Enteral Feeding. AB - This tutorial presents a systematic approach to the management of diarrhea in the critical care setting. Diarrhea is a common and prevalent problem in critically ill patients. Despite the high prevalence, its management is far from simple. Professionals are confronted with a myriad of definitions based on frequency, consistency, and volume. The causes are complex and multifactorial, yet enteral tube feeding formula is believed to be the perpetrator. Potential causes for diarrhea are discussed, and 3 case reports provide context to examine the treatment from a nutrition perspective. Each scenario is comprehensively addressed discussing potential causes and providing specific clinical strategies contributing to improved bowel function in this patient group. The approach used for diarrhea management is based on a complete understanding of enteral tube formula, their composition, and their impact in the presence of gut dysfunction. Choosing the right feeding formula may positively influence bowel function and contribute to improved nutrition. PMID- 27271712 TI - Ovalbumin expression in the oviduct magnum of hens is related to the rate of egg laying and shows distinct stress-type-specific responses. AB - Three trials were performed to evaluate the association of ovalbumin (OVA) abundance in the oviduct magnum with egg production and the underlying regulatory mechanism by glucocorticoids. In trial 1, twenty Hy-Line Brown layers (56-60 weeks of age) with different combinations (n = 5/combination) of laying rate (high or low) and egg weight (high or low) were selected from an initial group of 300. An upregulated expression of magnum OVA was observed (p < 0.05) in hens with higher laying rate, regardless of egg weight. In trial 2, eighty Hy-Line Brown layers (80-90 weeks of age) were subjected to the forced moulting (n = 8). The abundance of OVA transcript and protein in the magnum was significantly decreased during moulting (p < 0.01), and the same was true for laying rate (p < 0.01) and serum oestrogen (p < 0.05). In trial 3, forty-five 56-week-old Hy-Line Brown layers were kept individually (n = 15) in the following conditions for 10 days: constant optimal ambient temperature at 23 degrees C and ad libitum feeding, high ambient temperature at 32 degrees C for 6 h/day (10:00-16:00) and ad libitum feeding (32AL), and constant optimal ambient temperature at 23 degrees C and pair-fed to the 32AL hens. In spite of elevated corticosterone in circulation, OVA synthesis, blood oestrogen and laying rate were not affected by heat exposure (p > 0.05). These results allow concluding that OVA expression in the oviduct magnum of hens is related to the rate of egg laying and shows distinct stress-type-specific responses. PMID- 27271710 TI - Exploration and Identification of Cortico-Cerebellar-Brainstem Closed Loop During a Motivational-Motor Task: an fMRI Study. AB - The cerebellum is involved not only in motor coordination, training, and memory, but also in cognition and emotion. Lobule VI in particular belongs to sensorimotor, salience, and executive cerebellar networks. This study aims to determine whether lobule VI would constitute an integrative interface between motor and cognitive/emotional circuits during a motor task with verbal encouragement, likely in conjunction with the basal ganglia (reward and motivational system). We used fMRI to identify specific recruitment of cerebellar and striatal systems during physical performance using two motor tasks with and without encouragement. We found that: (i) Force results were higher during verbal encouragement than during basal condition in all participants. (ii) The anterior part of the right lobule VI was activated by motor execution in both tasks, while its posterior part was specifically activated by verbal encouragement. (iii) The closed-connectivity loop maintained motivation induced by verbal encouragement between cerebral and cerebellar through the red nucleus and striatal network. Therefore, right lobule VI is a hub-controlling sensorimotor and motivates aspects of motor performance in relation with the red nucleus and the ventral striatum. These results could have important implications for extrapyramidal and multisystem degenerative diseases. PMID- 27271713 TI - [Aortic valve replacement with stentless bioprosthesis]. AB - AIM: To evaluate prospectively the hemodynamic performance of "BioLAB Mono" stentless bioprosthesis implanted into aortic position. MATERIAL AND METHODS: Twenty seven patients (mean age 71 (67; 73); 17 women) with severe aortic stenosis underwent aortic valve replacement with "BioLAB Mono" stentless bioprosthesis from 2012 to 2014. The valves were implanted into supra-annular position using continuous polypropylene suture. RESULTS: In the early postoperative period 1 patient (3.7%) died for acute heart failure. The mean aortic cross-clamping time was 81 (75; 90) min. Echocardiographic peak pressure gradient were 18 (16; 23) mmHg (postoperative). There were no cases of valve dysfunction in early postoperative period. Level of thrombocytes recovered after 10 days postoperatively. CONCLUSION: "BioLAB Mono" aortic bioprosthesis implantation is easy and reproducible. The valve has excellent hemodynamic performance in early postoperative period. PMID- 27271711 TI - Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks. AB - Hereditary spastic paraplegia comprises a wide and heterogeneous group of inherited neurodegenerative and neurodevelopmental disorders resulting from primary retrograde dysfunction of the long descending fibers of the corticospinal tract. Although spastic paraparesis and urinary dysfunction represent the most common clinical presentation, a complex group of different neurological and systemic compromise has been recognized recently and a growing number of new genetic subtypes were described in the last decade. Clinical characterization of individual and familial history represents the main step during diagnostic workup; however, frequently, few and unspecific data allows a low rate of definite diagnosis based solely in clinical and neuroimaging basis. Likewise, a wide group of neurological acquired and inherited disorders should be included in the differential diagnosis and properly excluded after a complete laboratorial, neuroimaging, and genetic evaluation. The aim of this review article is to provide an extensive overview regarding the main clinical and genetic features of the classical and recently described subtypes of hereditary spastic paraplegia (HSP). PMID- 27271714 TI - [Reconstructive surgery of aortic arch interruption in adults]. AB - AIM: To evaluate surgical results in adults with aortic arch interruption. MATERIAL AND METHODS: Seven patients with aortic arch interruption were operated. Two of them (28.6%) underwent aortic arch repair using allograft, 4 (57.21%) - distal arch and proximal descending aortic replacement, 1 (14.3%) - supra coronary ascending aortic, aortic arch and proximal descending aortic replacement. All operations were performed under moderate hypothermia (25 degrees S), circulatory arrest with unilateral cerabral perfusion 8-10 ml/kg/min via innominate artery and pressure 69.6+/-14.7 mm Hg in arterial. RESULTS: Cardiopulmonary bypass (CPB) time was 242+/-36.1 min, aortic cross-clamping - 110.7+/-40.4 min, circulatory arrest - 58.6+/-17.9 min. There were no cases of renal insufficiency, vascular lesion of brain and spinal cord, cardiac events. Resternotomy for bleeding was performed in 1 (14.3%) case. Sufficient descending aortic lumen was achieved in 100% according to CT postoperatively. Peak descending aortic pressure gradient after repair with allograft was 29+/-1.4 mm Hg, after aortic replaement - 10+/-4.2 mm Hg. Postoperative and in-hospital 30 day mortality was absent. CONCLUSION: Reconstructive surgery for aortic arch interruption in adults is effective approach with good clinical and hemodynamic results. PMID- 27271715 TI - [Evolution of diagnostic methods for cicatrical tracheal stenosis and tracheomalacia]. AB - AIM: To analyze the role of ray functional computerized diagnostic technologies in assessment of the state of tracheal wall in cicatricial stenosis. MATERIAL AND METHODS: We examined 45 patients with cicatricial tracheal stenosis during August 2013 -- March 2015. Fibrobronchoscopy, multislice computerized tomography, magnetic resonance imaging and lungs function examination were performed. For the first time dynamic (functional) CT and MRI were included in research algorithm. These techniques have not been used for cicatricial stenosis and tracheomalacia in our country until this moment. Circular resection with anastomosis was made in 38 patients and stage reconstructions were preferred in 7 cases. Last ones had advanced tracheomalacia on the background of cicatrical stenosis that forced to abandon from tracheal resection. So time to treatment and incidence of complications and recurrences were reduced and the results were improved. CONCLUSION: Endoscopy remains the main method of diagnosis of tracheal stenosis despite its invasiveness. Data of cicatrical transformation of tracheal wall per se can be obtained non-invasively using dynamic CT and MRI. These techniques help to identify or exclude tracheomalacia. They potentially complement fibrobronchoscopy and may be preferable to assess perioperative intramural pathological changes of the trachea. PMID- 27271716 TI - [Hyperthermic intraperitoneal chemotherapy combined with cytoreductive procedure in patients with peritoneal pseudomyxoma]. AB - AIM: To study the results of intraperitoneal chemoperfusion combined with cytoreductive procedure in patients with peritoneal pseudomyxoma. MATERIAL AND METHODS: For the period 2006--2015 seven patients with peritoneal pseudomyxoma underwent aggressive treatment using hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure at the Department of General Oncology of N.N. Petrov Research Institute of Oncology. RESULTS: Two patients had postoperative complications. One of them died after 12 days postoperatively. Features of postoperative complications were predominantly determined by volume of cytoreduction. Advanced tumoral process caused death in 2 patients additionally. Other patients are still alive during 4--28 months after surgery. CONCLUSION: Hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure is advisable for peritoneal pseudomyxoma to improve survival. Optimal cytoreduction should be developed in researches with large number of patients to decrease incidence of complications. PMID- 27271717 TI - [Efficiency of local cement reinforcing antibacterial implants in surgical treatment of long bones chronic osteomyelitis]. AB - AIM: To present the results of treatment of long bones chronic osteomyelitis using local cement reinforcing antibacterial implant. MATERIAL AND METHODS: The implant is made intraoperatively using polymethylmethacrylate. It was used in main group (n=30), while conventional treatment was applied in comparison group (n=30). RESULTS: Better early and remote outcomes were shown in main group including more effective and earlier suppression of infectious process, more than 2-fold decrease of recurrent infection incidence, minimization of risk of pathological fracture due to internal reinforcement, early recovery of extremity's function, creation of favorable conditions for bone structures restoration, substitution of post-resection bone defect and following organotypic reorganization of bone tissue. PMID- 27271718 TI - [Total mesorectal excision in rectal cancer management: laparoscopic or transanal?]. AB - AIM: To evaluate and compare intraoperative features, early surgical outcomes, quality of excised specimen after laparoscopic and transanal total mesorectal excision (LA-TME and TA-TME). MATERIAL AND METHODS: Prospective randomized study included 45 patients with confirmed rectal adenocarcinoma (cT2-4N0-2M0) since October 2013. LA-TME and TA-TME groups consisted of 23 and 22 patients respectively. Inclusion criteria were patients with primary-operable rectal cancer and satisfactory response after neoadjuvant chemo- and radiotherapy. Both groups were comparable in stages of cancer, age and body mass index (BMI). Median length from anal edge was 6.5 cm and 7 cm in TA-TME and LA-TME groups respectively. There was significantly greater number of patients after chemo- and radiotherapy in TA-TME group (86% vs. 48%, p=0.006). RESULTS: Surgery time was 305 and 320 minutes in LA-TME and TA-TME groups recpectively, median blood loss - less than 100 ml. Mean hospital-stay was 8.0 days in both groups. Each group had 1 conversion including laparoscopic procedure in TA-TME group. Transanal extraction of specimen was performed in 86% vs. 48% in TA-TME and LA-TME groups respectively (p=0.021). Complications (Clavien-Dindo sclale) were observed in 27% and 26% in TA-TME and LA-TME groups respectively without statistically significance. Complications IIIb, IVb and V degrees were not diagnosed in TA-TME group. Also in this group "good", "satisfactory" and "unsatisfactory" quality of TME was obtained in 68%, 14% and 18% of cases. At the same time in LA-TME group these values were 74%, 9% and 17% respectively (p=0.859). One of operated patients had "positive" lateral edge (TA-TME). Median distal edge of resection was 21 mm and 23 mm in TA-TME and LA-TME groups respectively. CONCLUSION: Preliminary data show comparable early outcomes after transanal and laparoscopic techniques. Laparotomy and associated compications are avoided in case of transanal extraction of specimen. Further researches are necessary to study functional and long-term results. PMID- 27271719 TI - [Types of infectious complications exciters in recipients of related kidneys]. AB - AIM: To investigate the nature of microflora causing an infectious-inflammatory complications in recipients of related kidney in the early postoperative period and to substantiate the effectiveness of antibiotic prophylaxis and antibiotic therapy depending on pathogen type with the determination of its sensitivity to antimicrobial agents. MATERIAL AND METHODS: The medical records of 255 patients who underwent kidney transplantation from a living related donor from 2007 to 2014 were analyzed. Foci of infection were sanitized preoperatively to prevent infectious complications in post-transplantation period. Immunosuppression induction was achieved using 2-fold administration of Kempas or Simulect. Corticosteroids, ciclosporin, prograf, advagraf, myfortic, neoral, sertican were used for routine immunosuppression. Complications after kidney transplantation were detected in 65 (25.5%) patients including 38 (14.9%) infectious and 27 (10.6%) non-infectious complications. The material for microbiological examination included blood, urine, sputum, wound discharge, bronchial lavage. Extraction and identification of microorganisms were carried out according to conventional techniques as well as using automatic Vitec-2 Compact analizer ("BioMeriex", France). Sensitivity to antibiotics was determined using Vitek-2 Compact analyzer. The functional aspects of transplanted kidney were studied in 255 patients. Normal and decreased function of kidney was observed in 221 (86.6%) and 30 (11.8%) cases respectively. Transplantant did not function in 4 (1.57%) patients. RESULTS: The probability of infection is highest in the early postoperative period. Risk factors were inadequate and prolonged antibiotic therapy, unrecognized infection postoperatively. The main problem in renal transplant recipients is urinary tract infection (90% of patients). PMID- 27271720 TI - [Integrated approach to correction enteral insufficiency in early postoperative period]. AB - AIM: The purpose of the research was to study the effectiveness of enteral insufficiency correction at an acute peritonitis by applying minimally invasive techniques, electrical stimulation and rehabilitation of the bowel and abdominal intestine using Remaxol drug. MATERIAL AND METHODS: The analysis of the results of clinical and laboratory examination and treatment of 110 patients with acute diffuse peritonitis. In the comparison group (62 patients) in the early postoperative period applied standardized treatment, including software reorganization of the abdominal cavity, in the study group (48 patients) -- a comprehensive treatment that includes software laparoscopic sanation abdominal electrical stimulation of the duodenum, and intra-abdominal (single dose, 200 ml), and intracolonic (200 ml, 2 times daily) administration Remaxol. It was noted a significant improvement in treatment outcomes, including reduced mortality by 2.3 times, the shortening of hospital stay by 1.3 times. RESULTS: The major component of the positive effect of the developed scheme of therapy is its ability to promptly arrest the effects of enteral insufficiency, maintain the functional status of the liver. The relatively rapid recovery of motor and intestinal barrier function leads to a lowering of enteral insufficiency syndrome, which along with increased liver detoxification ability underlies the significant reduction of endogenous intoxication in three days. An important contribution to the effectiveness of the treatment makes intra and intracolonic administration Remaxol. The drug, possessing antioxidant, antihypoxic, hepatoprotective effects, contributes to the relatively rapid improvement of the barrier function of the peritoneum and intestines, detoxification ability of the liver recovery that significantly contributes to the relief of endogenous intoxication. PMID- 27271721 TI - [Substantiation of the system of thrombus formation prevention in treatment of patients with hip joint pathology against the background of arterial insufficiency of the lower extremities]. AB - AIM: To evaluate effectiveness of electroneurostimulation of the shin muscles as a constituent part of the prevention of TEC in the hip joint pathology at the hospital stage of treatment. MATERIAL AND METHODS: With this purpose, there was conducted the extended comparative analysis of the parameters of the blood coagulation system in 27 patients with pathology of the hip joints and the stated concomitant vascular insufficiency. The comparison group comprised 50 patients with uncomplicated pathology of the hip joint who underwent hip joint replacement surgery. In the patients of both groups the product dabigatran etexilate in the standard dosage (220 mg/day) was used for specific prevention. RESULTS: The authors managed to confirm qualitatively and quantitatively the effectiveness of the new variant of non-specific prevention in patients with a high risk of TEC development. Similar changes of the parameters of blood coagulation system were obtained at the use of electroneurostimulation of the shin muscles against the background of the use of the direct anticoagulant dabigatran etexilate. The numbers of thromboses in the group of patients with degenerative and dystrophic diseases of the hip joint with and without arterial insufficiency of the lower extremities are quite comparable (3.7 and 6%). Recanalization of the veins of the lower extremities in every individual case was achieved at the use of therapeutic doses of dabigatran etexilate (300 mg/day). The use of dabigatran etexilate permitted to minimize the risk of deep venous thrombosis (DVT) at hip interventions and contributed to recanalization of veins in recent thromboses in the postoperative period. PMID- 27271722 TI - Penicimenolides A-F, Resorcylic Acid Lactones from Penicillium sp., isolated from the Rhizosphere Soil of Panax notoginseng. AB - Five new 12-membered resorcylic acid lactone derivatives, penicimenolides A-E (1 5), one new ring-opened resorcylic acid lactone derivative penicimenolide F (6), and six known biogenetically related derivatives (7-12) were isolated from the culture broth of a strain of Penicillium sp. (NO. SYP-F-7919), a fungus obtained from the rhizosphere soil of Panax notoginseng collected from the Yunnan province of China. Their structures were elucidated by extensive NMR analyses, a modified Mosher's method, chemical derivatization and single crystal X-ray diffraction analysis. Compounds 2-4 exhibited potent cytotoxicity against the U937 and MCF-7 tumour cell lines and showed moderate cytotoxic activity against the SH-SY5Y and SW480 tumour cell lines. The substitution of an acetyloxy or 2 hydroxypropionyloxy group at C-7 significantly increased the cytotoxic activity of the resorcylic acid lactone derivatives. Subsequently, the possible mechanism of compound 2 against MCF-7 cells was preliminarily investigated by in silico analysis and experimental validation, indicating compound 2 may act as a potential MEK/ERK inhibitor. Moreover, proteomics analysis was performed to explore compound 2-regulated concrete mechanism underlying MEK/ERK pathway, which is still need further study in the future. In addition, compounds 2-4 and 7 exhibited a significant inhibitory effect on NO production induced by LPS. PMID- 27271723 TI - Radiographic templating of total hip arthroplasty for femoral neck fractures. AB - PURPOSE: The purpose of this study was to evaluate the use of pre-operative digital templating to minimize complications including limb length discrepancy (LLD), intraoperative fractures and early dislocations in patients with intracapsular femoral neck fractures. METHODS: We retrospectively compared 23 patients undergoing total hip arthroplasty (THA) for intracapsular femoral fractures with pre-operative digital templating and 48 patients without templating. RESULTS: The mean post-operative LLD was significantly lower in patients who had pre-operative templating than in the control group (6.7 vs. 11.5 mm, p = 0.023). Only three patients (13 %) with templating had LLD greater than 1.5 cm, compared to the 15 patients (31 %) without templating (p = 0.17). In eight cases the final femoral stem size matched the templated size, while 19 patients were within two size increments. Complications included one dislocation and one intra-operative fracture in the control group. CONCLUSION: The present study demonstrated that careful pre-operative planning may reduce LLD in patients undergoing THA due to intracapsular hip fractures. PMID- 27271724 TI - Outcomes of radical debridement versus no debridement for the treatment of thoracic and lumbar spinal tuberculosis. AB - PURPOSE: Whether radical debridement is necessary for the treatment of thoracic and lumbar tuberculosis is still questionable. The objective of this prospective randomized study was to compare the outcomes of radical debridement versus no debridement for the treatment of thoracic and lumbar tuberculosis. METHODS: Seventy-four thoracic and lumbar tuberculosis patients with a neurological function of grade D and E underwent surgery and received the same chemotherapy regiment from January 2009 to October 2014. All patients were divided into group A and B by taking the drawing of lots. In group A, radical debridement, bone graft, and instrumentation were performed. Isolated posterior instrumentation without debridement were performed in group B. The operative time, blood loss, visual analogue score (VAS), erythrocyte sedimentation rate (ESR), kyphotic angle, Frankel grading, fusion rate, and complications were evaluated. RESULTS: Group B had a better clinical outcome with regard to the operative time, blood loss, VAS score first week post-operatively, and the ESR value in the third and sixth month post-operatively than group A, and the differences between the two groups about those values all presented a significant difference (P < 0.05). However, no difference was observed between the two groups for the kyphotic angle (P = 0.088) and fusion rate (P = 0.164) at the final follow-up. Neurological function of all cases exhibited normal neurological function in the two groups at the final follow-up. Two cases of pulmonary infection and four cases of wound infection in group A. No serious complications were observed in group B. CONCLUSIONS: Isolated posterior instrumentation without debridement is a suitable treatment for selected patients because of minor surgical trauma, fewer complications, and spontaneous fusion. PMID- 27271725 TI - The effect of pentosanase on the solubilisation and degradation of arabinoxylan extracted from whole and refined wheat flour. AB - BACKGROUND: The quality improvement capability of pentosanase (Pn) for whole wheat Chinese steamed bread (CSB) is not as efficient as that for refined CSB. However, the underlying mechanism remains to be elucidated. In this work, water extractable arabinoxylan (WEAX) and water-unextractable solids (WUS) were extracted from whole and refined wheat flour, and then treated with Pn under the conditions similar to CSB-making. Solubilisation and degradation of arabinoxylan (AX) caused by Pn treatment were determined. RESULTS: WEAX from whole flour exhibited higher molecular weight than that from refined flour before and after the treatment with equivalent Pn. Compared with WUS from refined flour, WUS from whole flour had a much lower dissolution degree but the degradation of AX released from the WUS was more efficiently. Moreover, AX released from WUS for refined flour showed a higher Ara/Xyl ratio and the percentage of residual ferulic acid in WUS decreased more significantly. CONCLUSION: The difference in quality improvement degree for Pn in whole-wheat and refined CSB might be mainly explained by its effect on WUS. That is, Pn contributed much more to the solubilisation of WUS from refined flour but provoked degradation predominantly on AX solubilised from WUS isolated from whole flour. (c) 2016 Society of Chemical Industry. PMID- 27271726 TI - Cytotoxic effects of extract of Acmella oleraceae (Jambu) in Rhipicephalus microplus females ticks. AB - The present study analyzed the effects of different concentrations of the hexane extract of A. oleraceae (HEAO) (Jambu) on the germ cells of semi-engorged Rhipicephalus microplus female ticks, through a morpho-histological study, evaluating the effectiveness of the extract in the genesis of the individuals. To perform this analysis, 100 semi-engorged females were divided into five groups with 20 individuals each: groups I and II, respectively constituted by distilled water control and 50% ethanol + 1% DMSO, and groups III, IV, and V constituted by treatment with HEAO in the concentrations of 12.5, 25.0 and 50.0 mg/mL, respectively. All the ticks were immersed in the different concentrations of the extract or in distilled water for 5 minutes, dried and conditioned in BOD incubator for 7 days. The individuals of the treatment groups revealed the action of this extract showing alterations in the germ cells of the females from the different groups when compared with those from the groups I and II (control groups). These alterations were mainly related to the size and shape of the oocytes; number of yolk granules; presence, number, size and location of vacuoles in the cytoplasm of all the germ cells; and the presence of nuclear alterations in these cells as well. Thus, it was demonstrated that the concentrations of HEAO affected the germ cells of R. microplus ticks. The effects of the extract are similar to those caused by renowned and efficient chemical products used to control these ticks. Microsc. Res. Tech. 79:744-753, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27271727 TI - Silicone Breast Implant Rupture in a 70-year-old Woman Presenting with Multiple Superficial Nodules. PMID- 27271728 TI - Integrated Care for Older Adults Improves Perceived Quality of Care: Results of a Randomized Controlled Trial of Embrace. AB - BACKGROUND: All community-living older adults might benefit from integrated care, but evidence is lacking on the effectiveness of such services for perceived quality of care. OBJECTIVE: To examine the impact of Embrace, a community-based integrated primary care service, on perceived quality of care. DESIGN: Stratified randomized controlled trial. PARTICIPANTS: Integrated care and support according to the "Embrace" model was provided by 15 general practitioners in the Netherlands. Based on self-reported levels of case complexity and frailty, a total of 1456 community-living older adults were stratified into non-disease specific risk profiles ("Robust," "Frail," and "Complex care needs"), and randomized to Embrace or control groups. INTERVENTION: Embrace provides integrated, person-centered primary care and support to all older adults living in the community, with intensity of care dependent on risk profile. MEASUREMENTS: Primary outcome was quality of care as reported by older adults on the Patient Assessment of Integrated Elderly Care (PAIEC). Effects were assessed using mixed model techniques for the total sample and per risk profile. Professionals' perceived level of implementation of integrated care was evaluated within the Embrace condition using the Assessment of Integrated Elderly Care. KEY RESULTS: Older adults in the Embrace group reported a higher level of perceived quality of care than those in the control group (B = 0.33, 95 % CI = 0.15-0.51, ES d = 0.19). The advantages of Embrace were most evident in the "Frail" and "Complex care needs" risk profiles. We found no significant advantages for the "Robust" risk profile. Participating professionals reported a significant increase in the perceived level of implementation of integrated care (ES r = 0.71). CONCLUSIONS: This study shows that providing a population-based integrated care service to community-living older adults improved the quality of care as perceived by older adults and participating professionals. PMID- 27271729 TI - Describing Failure in a Clinical Clerkship: Implications for Identification, Assessment and Remediation for Struggling Learners. AB - BACKGROUND: In addition to training future members of the profession, medical schools perform the critical role of identifying students who are failing to meet minimum standards in core competencies. OBJECTIVE: To better understand reasons for failure in an internal medicine clerkship. DESIGN: A qualitative content analysis of letters describing reasons for students' failure. PARTICIPANTS: Forty three students (31 men) who failed the internal medicine clerkship at the University of Minnesota Medical School, 2002-2013. APPROACH: We conducted a qualitative content analysis of the 43 letters describing reasons for students' failure. We coded critical deficiencies and mapped them to the Physician Competency Reference Set (PCRS) competency domains and classified them into two categories: conduct (unprofessional behaviors) and knowledge and skills specific to the practice of medicine. We then calculated the frequency of each critical deficiency. We statistically tested for relationships between gender and critical deficiencies in each of the competency domains. KEY RESULTS: We coded 50 critical deficiencies with all codes mapping to a PCRS competency domain. The most frequently cited deficiencies were "insufficient knowledge" (79 % of students) and "inadequate patient presentation skills" (74 %). Students exhibited critical deficiencies in all eight competency domains, with the highest concentrations in Knowledge for Practice (98 %) and Interpersonal and Communication Skills (91 %). All students demonstrated deficiencies in multiple competencies, with 98 % having deficiencies in three or more. All 43 students demonstrated deficits in the knowledge and skills category, and 81 % had concurrent conduct issues. There were no statistically significant relationships between gender and critical deficiencies in any competency domain. CONCLUSIONS: This study highlights both the diversity and commonality of reasons that students fail a clinical clerkship. Knowing the range of areas where students struggle, as well as the most likely areas of difficulty, may aid faculty in identifying students who are failing and in developing remediation strategies. PMID- 27271730 TI - The Development and Evaluation of an Online Healthcare Toolkit for Autistic Adults and their Primary Care Providers. AB - BACKGROUND: The healthcare system is ill-equipped to meet the needs of adults on the autism spectrum. OBJECTIVE: Our goal was to use a community-based participatory research (CBPR) approach to develop and evaluate tools to facilitate the primary healthcare of autistic adults. DESIGN: Toolkit development included cognitive interviewing and test-retest reliability studies. Evaluation consisted of a mixed-methods, single-arm pre/post-intervention comparison. PARTICIPANTS: A total of 259 autistic adults and 51 primary care providers (PCPs) residing in the United States. INTERVENTIONS: The AASPIRE Healthcare toolkit includes the Autism Healthcare Accommodations Tool (AHAT)-a tool that allows patients to create a personalized accommodations report for their PCP-and general healthcare- and autism-related information, worksheets, checklists, and resources for patients and healthcare providers. MAIN MEASURES: Satisfaction with patient provider communication, healthcare self-efficacy, barriers to healthcare, and satisfaction with the toolkit's usability and utility; responses to open-ended questions. KEY RESULTS: Preliminary testing of the AHAT demonstrated strong content validity and adequate test-retest stability. Almost all patient participants (>94 %) felt that the AHAT and the toolkit were easy to use, important, and useful. In pre/post-intervention comparisons, the mean number of barriers decreased (from 4.07 to 2.82, p < 0.0001), healthcare self-efficacy increased (from 37.9 to 39.4, p = 0.02), and satisfaction with PCP communication improved (from 30.9 to 32.6, p = 0.03). Patients stated that the toolkit helped clarify their needs, enabled them to self-advocate and prepare for visits more effectively, and positively influenced provider behavior. Most of the PCPs surveyed read the AHAT (97 %), rated it as moderately or very useful (82 %), and would recommend it to other patients (87 %). CONCLUSIONS: The CBPR process resulted in a reliable healthcare accommodation tool and a highly accessible healthcare toolkit. Patients and providers indicated that the tools positively impacted healthcare interactions. The toolkit has the potential to reduce barriers to healthcare and improve healthcare self-efficacy and patient-provider communication. PMID- 27271731 TI - Correction: Atlantic Bluefin Tuna (Thunnus thynnus) Biometrics and Condition. AB - [This corrects the article DOI: 10.1371/journal.pone.0141478.]. PMID- 27271733 TI - Veranstaltungen. PMID- 27271732 TI - Male-female genotype interactions maintain variation in traits important for sexual interactions and reproductive isolation. AB - Prezygotic reproductive isolation can evolve quickly when sexual selection drives divergence in traits important for sexual interactions between populations. It has been hypothesized that standing variation for male/female traits and preferences facilitates this rapid evolution and that variation in these traits is maintained by male-female genotype interactions in which specific female genotypes prefer specific male traits. This hypothesis can also explain patterns of speciation when ecological divergence is lacking, but this remains untested because it requires information about sexual interactions in ancestral lineages. Using a set of ancestral genotypes that previously had been identified as evolving reproductive isolation, we specifically asked whether there is segregating variation in female preference and whether segregating variation in sexual interactions is a product of male-female genotype interactions. Our results provide evidence for segregating variation in female preference and further that male-female genotype interactions are important for maintaining variation that selection can act on and that can lead to reproductive isolation. PMID- 27271734 TI - Horizontal ECG in acute anterolateral myocardial infarction. AB - BACKGROUND: The present study aims to compare the amount of ST segment changes recorded by horizontal electrocardiography (hECG) with standard ECG (sECG) in patients with acute anterior and/or lateral ST segment elevation myocardial infarction (STEMI). METHODS: Consecutive eligible patients (n = 58) who were diagnosed with acute anterior and/or lateral STEMI were included in the study. After recording simultaneous sECG and hECG by placing precordial leads (V3-6) horizontally on the left 4th intercostal space, ST segment changes were compared. RESULTS: The mean ST segment changes (mV) on hECG were significantly higher than sECG in V4 (0.27 +/- 0.2 vs. 0.21 +/- 0.21, p = 0.001), V5 (0.21 +/- 0.17 vs. 0.12 +/- 0.16, p < 0.001) and V6 (0.09 +/- 0.1 vs. 0.04 +/- 0.12, p < 0.001), respectively. When hECG and sECG were compared in patients with BMI < 30 kg/m(2), mean ST segment changes (mV) on hECG were significantly higher than sECG in V4 (0.29 +/- 0.21 vs. 0.21 +/- 0.24, p = 0.004), V5 (0.22 +/- 0.19 vs. 0.13 +/- 0.17, p < 0.001) and V6 (0.11 +/- 0.11 vs. 0.04 +/- 0.11, p < 0.001), respectively. CONCLUSIONS: Mean ST segment changes in patients with anterior and/or lateral STEMI were significantly higher and easily detectable on hECG compared with sECG. We suggest that hECG be used in conjunction with sECG to diagnose anterior and lateral wall STEMI in cases of diagnostic doubt. PMID- 27271735 TI - Reducing Anemia Prevalence in Afghanistan: Socioeconomic Correlates and the Particular Role of Agricultural Assets. AB - This research aims to examine the socio-economic correlates of anemia in women, and potential sources of iron in household diets in Afghanistan. It also examines whether ownership of agricultural (particularly livestock) assets and their use in food production has a role in alleviating anaemia, especially where local markets may be inadequate. We analyse data from the 2010/11 Afghanistan Multiple Indicator Cluster Survey, estimating a logistic regression to examine how anemia status of women is associated with socio-economic covariates. A key result found is that sheep ownership has a protective effect in reducing anemia (prevalence odds ratio of sheep ownership on anemia of 0.83, 95% confidence interval (CI): 0.73-0.94) after controlling for wealth and other covariates. This association is found to be robust to alternative model specifications. Given the central role of red meat in heme iron provision and absorption of non-heme iron, we hypothesise that sheep ownership promotes mutton consumption from own-production in a setting where market-sourced provision of nutritious food is a challenge. We then use the 2011/12 National Risk and Vulnerability Assessment household data to understand the Afghan diet from the perspective of dietary iron provision, and to understand interactions between own-production, market sourcing and mutton consumption. Sheep ownership is found to increase the likelihood that a household consumed mutton (odds ratio of 1.27, 95% CI: 1.15-1.42), the number of days in the week that mutton was consumed (prevalence rate ratio of 1.24. 95% CI: 1.12-1.37) and the quantity of mutton consumed (7 grams/person/week). In the subsample of mutton consumers, households sourcing mutton mostly from own production consumed mutton 1.5 days more frequently on average than households relying on market purchase, resulting in 100 grams per person per week higher mutton intake. Thus this analysis lends support to the notion that the linkage between sheep ownership and anemia risk is at least partly due to consumption arising from own-production in the presence of market incompleteness. PMID- 27271736 TI - Medication Therapy Management Service for Patients with Parkinson's Disease: A Before-and-After Study. AB - BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease characterized by motor manifestations, autonomic and neurological disorders and sensorial symptoms. Medication therapy management (MTM) consists of a service undertaken by pharmacists to optimize pharmacological therapy results. This way, the pharmacist monitors the treatment prescribed by the doctor and formulates a healthcare plan to guarantee the treatment's effectiveness, safety and convenience, thereby improving the patient's quality of life (QoL). OBJECTIVE: To analyze the effect of MTM upon medicine-related problems, motor symptoms, autonomic disorders and QoL of patients with Parkinson's disease, and describe the pharmaceutical interventions. METHODS: Quasi-experimental uncontrolled before-and-after study carried out between September 2012 and March 2013 in a community pharmacy. Pharmacotherapy data were collected from medical prescriptions, patient diaries, medical charts and all the medicines (over-the-counter and prescription) brought by the patients to the appointment with the pharmacist. The medicine-related problems were classified as indication, effectiveness, safety and adherence. Adherence was measured through clinical interviews and the Morisky questionnaire. PD symptoms were assessed according to the patients' and/or caregivers' perceptions about the On/Off state of the motor symptoms and relief of the nonmotor symptoms. QoL was assessed using the PDQ-39 scores. The interventions were targeted to patients/caregivers and/or doctors, with pharmacological and non pharmacological measures. RESULTS: Seventy patients were followed up, showing a decrease in medicine-related problems (1.67 +/- 1.34 to 0.8 +/- 0.9 (p < 0.001), positive impact on adherence (from 37 to 10 non-adherent patients, p < 0.001), QoL improvement related to emotional wellbeing (p = 0.012) and autonomic disorder. Most interventions were performed directly with the patients (73.8%), including non-pharmacological guidance (28.5%), pharmacological guidance (24.3%) and rescheduling (13.6%). CONCLUSIONS: To carry out MTM with PD patients, the pharmacist's expertise needs to transcend the technical knowledge about the PD pharmacological treatment. The study showed a positive effect with a decrease in the medicine-related problems after the interventions, especially improving adherence and patients' QoL. PMID- 27271737 TI - Peptide aromatic interactions modulated by fluorinated residues: Synthesis, structure and biological activity of Somatostatin analogs containing 3 (3',5'difluorophenyl)-alanine. AB - Somatostatin is a 14-residue peptide hormone that regulates the endocrine system by binding to five G-protein-coupled receptors (SSTR1-5). We have designed six new Somatostatin analogs with L-3-(3',5'-difluorophenyl)-alanine (Dfp) as a substitute of Phe and studied the effect of an electron-poor aromatic ring in the network of aromatic interactions present in Somatostatin. Replacement of each of the Phe residues (positions 6, 7 and 11) by Dfp and use of a D-Trp8 yielded peptides whose main conformations could be characterized in aqueous solution by NMR. Receptor binding studies revealed that the analog with Dfp at position 7 displayed a remarkable affinity to SSTR2 and SSTR3. Analogs with Dfp at positions 6 or 11 displayed a pi-pi interaction with the Phe present at 11 or 6, respectively. Interestingly, these analogs, particularly [D-Trp8,L-Dfp11]-SRIF, showed high selectivity towards SSTR2, with a higher value than that of Octreotide and a similar one to that of native Somatostatin. PMID- 27271738 TI - Supporting Regularized Logistic Regression Privately and Efficiently. AB - As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc. PMID- 27271739 TI - Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders. AB - Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei DeltatonB Deltahcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain. PMID- 27271740 TI - Role of Iron Uptake Systems in Pseudomonas aeruginosa Virulence and Airway Infection. AB - Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and chronic lung infections in cystic fibrosis patients. Iron is essential for bacterial growth, and P. aeruginosa expresses multiple iron uptake systems, whose role in lung infection deserves further investigation. P. aeruginosa Fe(3+) uptake systems include the pyoverdine and pyochelin siderophores and two systems for heme uptake, all of which are dependent on the TonB energy transducer. P. aeruginosa also has the FeoB transporter for Fe(2+) acquisition. To assess the roles of individual iron uptake systems in P. aeruginosa lung infection, single and double deletion mutants were generated in P. aeruginosa PAO1 and characterized in vitro, using iron-poor media and human serum, and in vivo, using a mouse model of lung infection. The iron uptake-null mutant (tonB1 feoB) and the Fe(3+) transport mutant (tonB1) did not grow aerobically under low-iron conditions and were avirulent in the mouse model. Conversely, the wild type and the feoB, hasR phuR (heme uptake), and pchD (pyochelin) mutants grew in vitro and caused 60 to 90% mortality in mice. The pyoverdine mutant (pvdA) and the siderophore-null mutant (pvdA pchD) grew aerobically in iron-poor media but not in human serum, and they caused low mortality in mice (10 to 20%). To differentiate the roles of pyoverdine in iron uptake and virulence regulation, a pvdA fpvR double mutant defective in pyoverdine production but expressing wild type levels of pyoverdine-regulated virulence factors was generated. Deletion of fpvR in the pvdA background partially restored the lethal phenotype, indicating that pyoverdine contributes to the pathogenesis of P. aeruginosa lung infection by combining iron transport and virulence-inducing capabilities. PMID- 27271741 TI - Investigating the Relatedness of Enteroinvasive Escherichia coli to Other E. coli and Shigella Isolates by Using Comparative Genomics. AB - Enteroinvasive Escherichia coli (EIEC) is a unique pathovar that has a pathogenic mechanism nearly indistinguishable from that of Shigella species. In contrast to isolates of the four Shigella species, which are widespread and can be frequent causes of human illness, EIEC causes far fewer reported illnesses each year. In this study, we analyzed the genome sequences of 20 EIEC isolates, including 14 first described in this study. Phylogenomic analysis of the EIEC genomes demonstrated that 17 of the isolates are present in three distinct lineages that contained only EIEC genomes, compared to reference genomes from each of the E. coli pathovars and Shigella species. Comparative genomic analysis identified genes that were unique to each of the three identified EIEC lineages. While many of the EIEC lineage-specific genes have unknown functions, those with predicted functions included a colicin and putative proteins involved in transcriptional regulation or carbohydrate metabolism. In silico detection of the Shigella virulence plasmid (pINV), which is essential for the invasion of host cells, demonstrated that a form of pINV was present in nearly all EIEC genomes, but the Mxi-Spa-Ipa region of the plasmid that encodes the invasion-associated proteins was absent from several of the EIEC isolates. The comparative genomic findings in this study support the hypothesis that multiple EIEC lineages have evolved independently from multiple distinct lineages of E. coli via the acquisition of the Shigella virulence plasmid and, in some cases, the Shigella pathogenicity islands. PMID- 27271742 TI - Chelation of Membrane-Bound Cations by Extracellular DNA Activates the Type VI Secretion System in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa employs its type VI secretion system (T6SS) as a highly effective and tightly regulated weapon to deliver toxic molecules to target cells. T6SS-secreted proteins of P. aeruginosa can be detected in the sputum of cystic fibrosis (CF) patients, who typically present a chronic and polymicrobial lung infection. However, the mechanism of T6SS activation in the CF lung is not fully understood. Here we demonstrate that extracellular DNA (eDNA), abundant within the CF airways, stimulates the dynamics of the H1-T6SS cluster apparatus in Pseudomonas aeruginosa PAO1. Addition of Mg(2+) or DNase with eDNA abolished such activation, while treatment with EDTA mimicked the eDNA effect, suggesting that the eDNA-mediated effect is due to chelation of outer membrane-bound cations. DNA-activated H1-T6SS enables P. aeruginosa to nonselectively attack neighboring species regardless of whether or not it was provoked. Because of the importance of the T6SS in interspecies interactions and the prevalence of eDNA in the environments that P. aeruginosa inhabits, our report reveals an important adaptation strategy that likely contributes to the competitive fitness of P. aeruginosa in polymicrobial communities. PMID- 27271743 TI - EseE of Edwardsiella tarda Augments Secretion of Translocon Protein EseC and Expression of the escC-eseE Operon. AB - Edwardsiella tarda is an important Gram-negative pathogen that employs a type III secretion system (T3SS) to deliver effectors into host cells to facilitate bacterial survival and replication. These effectors are translocated into host cells through a translocon complex composed of three secreted proteins, namely, EseB, EseC, and EseD. The secretion of EseB and EseD requires a chaperone protein called EscC, whereas the secretion of EseC requires the chaperone EscA. In this study, we identified a novel protein (EseE) that also regulates the secretion of EseC. An eseE deletion mutant secreted much less EseC into supernatants, accompanied by increased EseC levels within bacterial cells. We also demonstrated that EseE interacted directly with EseC in a pulldown assay. Interestingly, EseC, EseE, and EscA were able to form a ternary complex, as revealed by pulldown and gel filtration assays. Of particular importance, the deletion of eseE resulted in decreased levels of EseB and EseD proteins in both the bacterial pellet and supernatant fraction. Furthermore, real-time PCR assays showed that EseE positively regulated the transcription of the translocon operon escC-eseE, comprising escC, eseB, escA, eseC, eseD, and eseE These effects of EseE on the translocon components/operon appeared to have a functional consequence, since the DeltaeseE strain was outcompeted by wild-type E. tarda in a mixed infection in blue gourami fish. Collectively, our results demonstrate that EseE not only functions as a chaperone for EseC but also acts as a positive regulator controlling the expression of the translocon operon escC-eseE, thus contributing to the pathogenesis of E. tarda in fish. PMID- 27271744 TI - Intravenous Inoculation with Chlamydia muridarum Leads to a Long-Lasting Infection Restricted to the Gastrointestinal Tract. AB - Chlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, it remains unclear whether the chlamydial organisms can be introduced into the gastrointestinal tract via pathways independent of the oral and anal routes. We have recently shown that Chlamydia muridarum spreads from the genital tract to the gastrointestinal tract potentially via the circulatory system. To test whether hematogenous C. muridarum can spread to and establish a long-lasting colonization in the mouse gastrointestinal tract, we inoculated mice intravenously with a luciferase-expressing C. muridarum strain and monitored its distribution. After tail vein inoculation, most luciferase-generated bioluminescence signals were detected in the mouse abdominal area throughout the experiment. The ex vivo imaging revealed that the abdominal signals came from the gastrointestinal tract tissues. Simultaneous monitoring of chlamydial organisms in individual organs or tissues revealed an initial stage of systemic spreading followed by a long-lasting infection in the gastrointestinal tract. A retro orbital vein inoculation of the C. muridarum organisms at a lower dose in a different mouse strain also led to colonization of the gastrointestinal tract. We have demonstrated that intravenous C. muridarum inoculation can result in colonization of the gastrointestinal tract, suggesting that the chlamydial organisms may use the sexual behavior-independent circulation pathway to infect the gastrointestinal tract. PMID- 27271745 TI - HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts. AB - High-temperature requirement protease A (HtrA) represents a family of serine proteases that play important roles in microbial biology. Unlike the genomes of most organisms, that of Borrelia burgdorferi notably encodes a single HtrA gene product, termed BbHtrA. Previous studies identified a few substrates of BbHtrA; however, their physiological relevance could not be ascertained, as targeted deletion of the gene has not been successful. Here we show that BbhtrA transcripts are induced during spirochete growth either in the stationary phase or at elevated temperature. Successful generation of a BbhtrA deletion mutant and restoration by genetic complementation suggest a nonessential role for this protease in microbial viability; however, its remarkable growth, morphological, and structural defects during cultivation at 37 degrees C confirm a high temperature requirement for protease activation and function. The BbhtrA deficient spirochetes were unable to establish infection of mice, as evidenced by assessment of culture, PCR, and serology. We show that transcript abundance as well as proteolytic processing of a borrelial protein required for cell fission and infectivity, BB0323, is impaired in BbhtrA mutants grown at 37 degrees C, which likely contributed to their inability to survive in a mammalian host. Together, these results demonstrate the physiological relevance of a unique temperature-regulated borrelial protease, BbHtrA, which further enlightens our knowledge of intriguing aspects of spirochete biology and infectivity. PMID- 27271746 TI - Interleukin-17 Pathophysiology and Therapeutic Intervention in Cystic Fibrosis Lung Infection and Inflammation. AB - Cystic fibrosis (CF) is characterized by an excessive neutrophilic inflammatory response within the airway as a result of defective cystic fibrosis transmembrane receptor (CFTR) expression and function. Interleukin-17A induces airway neutrophilia and mucin production associated with Pseudomonas aeruginosa colonization, which is associated with the pathophysiology of cystic fibrosis. The objectives of this study were to use the preclinical murine model of cystic fibrosis lung infection and inflammation to investigate the role of IL-17 in CF lung pathophysiology and explore therapeutic intervention with a focus on IL-17. Cftr-deficient mice (CF mice) and wild-type mice (WT mice) infected with P. aeruginosa had robust IL-17 production early in the infection associated with a persistent elevated inflammatory response. Intratracheal administration of IL-17 provoked a neutrophilic response in the airways of WT and CF animals which was similar to that observed with P. aeruginosa infection. The neutralization of IL 17 prior to infection significantly improved the outcomes in the CF mice, suggesting that IL-17 may be a therapeutic target. We demonstrate in this report that the pathophysiological contribution of IL-17 may be due to the induction of chemokines from the epithelium which is augmented by a deficiency of Cftr and ongoing inflammation. These studies demonstrate the in vivo contribution of IL-17 in cystic fibrosis lung disease and the therapeutic validity of attenuating IL-17 activity in cystic fibrosis. PMID- 27271747 TI - Glucosylation Drives the Innate Inflammatory Response to Clostridium difficile Toxin A. AB - Clostridium difficile is a major, life-threatening hospital-acquired pathogen that causes mild to severe colitis in infected individuals. The tissue destruction and inflammation which characterize C. difficile infection (CDI) are primarily due to the Rho-glucosylating toxins A and B. These toxins cause epithelial cell death and induce robust inflammatory signaling by activating the transcription factor NF-kappaB, leading to chemokine and cytokine secretion. The toxins also activate the inflammasome complex, which leads to secretion of the pyrogenic cytokine IL-1beta. In this study, we utilized glucosylation-deficient toxin A to show that activation of the inflammasome by this toxin is dependent on Rho glucosylation, confirming similar findings reported for toxin B. We also demonstrated that tissue destruction and in vivo inflammatory cytokine production are critically dependent on the enzymatic activity of toxin A, suggesting that inhibiting toxin glucosyltransferase activity may be effective in combating this refractory disease. PMID- 27271748 TI - Paediatric Multiple Sclerosis: Update on Diagnostic Criteria, Imaging, Histopathology and Treatment Choices. AB - Paediatric multiple sclerosis (MS) represents less than 5 % of the MS population, but patients with paediatric-onset disease reach permanent disability at a younger age than adult-onset patients. Accurate diagnosis at presentation and optimal long-term treatment are vital to mitigate ongoing neuroinflammation and irreversible neurodegeneration. However, it may be difficult to early differentiate paediatric MS from acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD), as they often have atypical presentation that differs from that of adult-onset MS. The purpose of this review is to summarize the updated views on diagnostic criteria, imaging, histopathology and treatment choices. PMID- 27271749 TI - Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer. AB - BACKGROUND: To assess the role of radiation dose intensification with simultaneous integrated boost guided by 18-FDG-PET/CT in pre-operative chemo radiotherapy (ChT-RT) for locally advanced rectal cancer. METHODS: A prospective study was approved by the Internal Review Board. Inclusion criteria were: age >18 years old, World Health Organization performance status of 0-1, locally advanced histologically proven adenocarcinoma of the rectum within 10 cm of the anal verge, signed specific informed consent. High-dose volumes were defined including the hyper-metabolic areas of 18-FDG-PET/CT of primary tumor and the corresponding mesorectum and/or pelvic nodes with at least a standardized uptake values (SUV) of 5. A dose of 60 Gy/30 fractions was delivered. A total dose of 54 Gy/30 fractions was delivered to prophylactic areas. Capecitabine was administered concomitantly with RT for a dose of 825 mg/mq twice daily for 5 days/every week. RESULTS: Between September 2011 and July 2015 fortypatients were recruited. At the time of the analysis, median follow up was 20 months (range 5-51). The median interval from the end of ChT-RT to surgery was 9 weeks (range 8-12). Thirty-seven patients (92.5 %) were submitted to sphincter preservation. Tumor Regression Grade (Mandard scale) was recorded as follows: grade 1 in 7 (17.5 %), grade 2 in 17 (42.5 %), grade 3 in 15 (37.5 %) and grade 4 in 1 (2.5 %). Post-surgical circumferential resection margin was negative in all patients. A tumor downstaging was reported in 62.5 % (95 % CI: 0.78-0.47). A nodes downstaging was registered in 85 % (95 % CI: 0.55-0.25). 18-FDG-PET/CT was not able to predict pCR. No correlation was found between pre-treatment SUV-max values and pCR. A metabolic tumor volume >127 cc was related to ypT >=2 (p 0.01). Patients with TRG >2 had higher tumor lesion glycolysis values (p 0.05). CONCLUSION: Preliminary results did not confirm some advantages in terms of primary tumor downstaging/downsizing compared to conventional schedules reported in historical series. The role of 18-FDG-PET/CT in neoadjuvant rectal cancer management needs to be confirmed in further investigations. Long terms results are necessary. PMID- 27271750 TI - A Novel ICU Hand-Over Tool: The Glass Door of the Patient Room. AB - BACKGROUND: Poor communication among health-care providers is cited as the most common cause of sentinel events involving patients. Patient care in the critical care setting is incredibly complex. A consistent care plan is necessary between day/night shift teams and among bedside intensive care unit (ICU) nurses, consultants, and physicians. Our goal was to create a novel, easily accessible communication device to improve ICU patient care. METHODS: This communication improvement project was done at an academic tertiary surgical/trauma/mixed 36-bed ICU with an average of 214 admissions per month. We created a glass door template embossed on the glass that included 3 columns for daily goals to be written: "day team," "night team," and "surgery/consultant team." Assigned areas for tracking "lines," "antibiotics," "ventilator weaning," and "Deep vein thrombosis (DVT) screening" were included. These doors are filled out/updated throughout the day by all of the ICU providers. All services can review current plans/active issues while evaluating the patient at the bedside. Patient-identifying data are not included. We retrospectively reviewed all ICU safety reported events over a 4 year period (2 years prior/2 years after glass door implementation) for specific handover communication-related errors and compared the 2 cohorts. RESULTS: Information on the glass doors is entered daily on rounds by all services. Prior to implementation, 7.96% of reported errors were related to patient handover communication errors. The post glass-door era had 4.26% of reported errors related to patient handover communication errors with a relative risk reduction of 46.5%. Due to its usefulness, this method of communication was quickly adopted by the other critical care services (cardiothoracic, medical, neurology/neurosurgery, cardiology) at our institution and is now used for over 150 ICU beds. CONCLUSIONS: Our glass door patient handover tool is an easily adaptable intervention that has improved communication leading to an overall decrease in the number of handover communication errors. PMID- 27271752 TI - Novel nuclear hENT2 isoforms regulate cell cycle progression via controlling nucleoside transport and nuclear reservoir. AB - Nucleosides participate in many cellular processes and are the fundamental building blocks of nucleic acids. Nucleoside transporters translocate nucleosides across plasma membranes although the mechanism by which nucleos(t)ides are translocated into the nucleus during DNA replication is unknown. Here, we identify two novel functional splice variants of equilibrative nucleoside transporter 2 (ENT2), which are present at the nuclear envelope. Under proliferative conditions, these splice variants are up-regulated and recruit wild type ENT2 to the nuclear envelope to translocate nucleosides into the nucleus for incorporation into DNA during replication. Reduced presence of hENT2 splice variants resulted in a dramatic decrease in cell proliferation and dysregulation of cell cycle due to a lower incorporation of nucleotides into DNA. Our findings support a novel model of nucleoside compartmentalisation at the nuclear envelope and translocation into the nucleus through hENT2 and its variants, which are essential for effective DNA synthesis and cell proliferation. PMID- 27271754 TI - Posterior cruciate-substituting total knee replacement recovers the flexion arc faster in the early postoperative period in knees with high varus deformity: a prospective randomized study. AB - INTRODUCTION: Posterior cruciate retention (CR) and substitution (PS) has been controversial in knee replacement surgery. Satisfactory medium and long-term results have been reported in knees with and without deformity but there are limited studies about early functional comparison in terms of recovery of flexion arc, stair activity, walking ability and straight leg raising, especially, in early postoperative period in knees with deformity. Therefore, we aimed to compare the flexion arc in CR and PS knees in postoperative first year including early postoperative days prospectively. METHODS: Consecutive patients with a deformity of >10 degrees were included and allocated to CR and PS groups randomly. KSS and Feller-patella scores were recorded both preoperatively and postoperatively (1st, 2nd, 3rd and 12th months). Flexion and extension were measured both preoperatively and postoperatively (1st, 2nd, 3rd day and discharge day as well as 1st, 2nd, 3rd and 12th months). Visual analog scale (VAS) was recorded postoperatively at the 1st, 2nd, 3rd and discharge day and at 1st, 2nd, 3rd and 12th months. The walking ability, stair activity and straight leg raising were recorded. Patients were also examined at the last visit with minimum 7-year follow-up with KSS, Feller-patella and VAS scores. Their mean flexion arcs were measured and recorded. RESULTS: There were 61 TKR evaluated. KSS knee and function scores at the 3rd month and KSS Knee Score at 1st year were superior in PS knees (p = 0.029, p = 0.046, p = 0.026). Flexion arc was found larger on day 1, 2, 3 and discharge day, and at 1st, 2nd, 3rd and 12th month in PS group (p = 0.048, p = 0.002, p = 0.027, p = 0.043, p = 0.014, p = 0.003, p = 0.002, p = 0.018). Walking and stair activity showed no difference but straight leg raising was better in CR knees (p = 0.02). Mean flexion arc was larger in PS knees at the last visit after 7 years (119.0 degrees +/- 7.5 degrees in PS and 113.8 degrees +/- 8.7 degrees in CR, p = 0.02). There was no revision required in that time interval. The other parameters were similar between groups. CONCLUSIONS: PS knees gained active flexion arc faster and larger. But straight leg raising activity recovered early in CR knees. Both types of prosthesis produced satisfactory outcome. PS and CR TKRs can be performed with the same performance in osteoarthritic knees even with high varus deformity. LEVEL OF EVIDENCE: Prospective Randomized Controlled Trial, Level II. PMID- 27271755 TI - A treatment strategy to avoid iatrogenic Pipkin type III femoral head fracture dislocations. AB - INTRODUCTION: Reduction is urgently required in cases of traumatic hip dislocation to decrease the risk of avascular necrosis of the femoral head. However, successful reduction may not always be feasible for hip dislocations associated with femoral head fractures. This irreducibility may provoke further incidental fractures of the femoral neck with resultant Pipkin type III injuries. The purpose of this study was to describe an appropriate treatment strategy for irreducible femoral head fracture-dislocations. MATERIALS AND METHODS: We treated nine patients with irreducible hip dislocations with femoral head fractures (eight Pipkin type II and one type IV) for which reduction failed in the emergency room or operating theater. All of these cases required operative management. RESULTS: Five of the nine patients experienced femoral neck fractures after closed reduction were attempted. These five cases underwent joint replacement at the time of injury or after developing avascular necrosis of the femoral head. Analysis of radiographs and computed tomography (CT) scans revealed that the fractured femoral head was perched on the sharp angle of the posterior wall of the acetabulum in the irreducible hips. After recognizing the irreducibility, the other four cases underwent immediate open reduction without further attempts at closed reduction, which saved the natural hip joint without neck fracture or avascular necrosis. CONCLUSIONS: Repeated or forceful closed reduction of irreducible femoral head fracture-dislocation injuries may result in iatrogenic femoral neck fractures with Pipkin type III injuries. Before attempting reduction, careful examination of plain radiographs and CT images may be helpful for determining the safest treatment strategy. PMID- 27271753 TI - Cytokine responses and epithelial function in the intestinal mucosa. AB - Inflammatory diseases of mucosal organs are significantly influenced by the microenvironment in which they reside. Cytokines found within this microenvironment contribute significantly to endpoint functions of the mucosa. Studies dating back to the 1990s have revealed that epithelial cells are both a source as well as a target for numerous cytokines and that such signaling can substantially influence the outcome of mucosal disease, such as inflammatory bowel disease. Here, we will review literature regarding intestinal epithelial cells as sources and responders to cytokines found in the intestinal milieu. These studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation. PMID- 27271756 TI - Preliminary results of a new surgical technique in total knee arthroplasty (TKA) using the native ligament tension for femoral implant positioning in varus osteoarthritis. AB - PURPOSE: Individual implant alignment in total knee arthroplasty (TKA) has seen growing interest over the past years. This study therefore aimed to develop a surgical technique for implant alignment based on native ligament tension, and to present the results obtained using this technique. METHODS: 25 patients were included in this prospective study. Patient-specific instrumentation (PSI) was used for the resection of the extension gap. Ligament tension was measured after the removal of all accessible osteophytes. In the event of asymmetry, the distal femur resection was adjusted up to 2.5 degrees using an adjustable cutting block. The aim was to achieve a symmetrical extension gap without release, not a neutral leg axis. Femoral rotation was aligned on the basis of ligament tension. Patients were followed up to 3 months postoperatively. RESULTS: The postoperative whole-leg axis was 2.8 degrees +/- 1.6 degrees varus. Patients achieved a flexion of 118 degrees +/- 9 degrees , a Knee Score of 91.5 +/- 3.2 and a Function Score of 86.8 +/- 8.3 points. CONCLUSION: For the first time, the new surgical technique described here permits a ligament tension based femoral implant alignment together with PSI. It was shown to be safe, with encouraging clinical and radiological results. LEVEL OF EVIDENCE: Therapeutic study level IV. PMID- 27271758 TI - Size-dependent crystalline fluctuation and growth mechanism of bismuth nanoparticles under electron beam irradiation. AB - Advanced nanofabrication requires accurate tailoring of various nanostructures with the assistance of electron or ion beam irradiation. However, evolution of the nanostructures under the beam irradiation significantly affects the fabrication process. It is thus of paramount importance to study the evolution behaviors and growth mechanism of the nanostructures. In this study, bismuth nanoparticles were selected to investigate crystalline fluctuation under electron beam irradiation via transmission electron microscopy. The results disclose size dependent crystalline fluctuation of the nanoparticles. The particles exhibit crystalline and non-crystalline features for sizes of above 15 and below 4 nm, respectively, while a mixture of the two states is observed with sizes in between. The crystalline fluctuation facilitates the growth process of the particles when a crystalline particle is in contact with another non-crystalline one. This is promising for applications in nanofabrication where high quality interfaces are desired between two joining parts. PMID- 27271757 TI - A Novel Truncated Form of Serum Amyloid A in Kawasaki Disease. AB - BACKGROUND: Kawasaki disease (KD) is an acute vasculitis in children that can cause coronary artery abnormalities. Its diagnosis is challenging, and many cytokines, chemokines, acute phase reactants, and growth factors have failed evaluation as specific biomarkers to distinguish KD from other febrile illnesses. We performed protein profiling, comparing plasma from children with KD with febrile control (FC) subjects to determine if there were specific proteins or peptides that could distinguish the two clinical states. MATERIALS AND METHODS: Plasma from three independent cohorts from the blood of 68 KD and 61 FC subjects was fractionated by anion exchange chromatography, followed by surface-enhanced laser desorption ionization (SELDI) mass spectrometry of the fractions. The mass spectra of KD and FC plasma samples were analyzed for peaks that were statistically significantly different. RESULTS: A mass spectrometry peak with a mass of 7,860 Da had high intensity in acute KD subjects compared to subacute KD (p = 0.0003) and FC (p = 7.9 x 10-10) subjects. We identified this peak as a novel truncated form of serum amyloid A with N-terminal at Lys-34 of the circulating form and validated its identity using a hybrid mass spectrum immunoassay technique. The truncated form of serum amyloid A was present in plasma of KD subjects when blood was collected in tubes containing protease inhibitors. This peak disappeared when the patients were examined after their symptoms resolved. Intensities of this peptide did not correlate with KD associated laboratory values or with other mass spectrum peaks from the plasma of these KD subjects. CONCLUSIONS: Using SELDI mass spectrometry, we have discovered a novel truncated form of serum amyloid A that is elevated in the plasma of KD when compared with FC subjects. Future studies will evaluate its relevance as a diagnostic biomarker and its potential role in the pathophysiology of KD. PMID- 27271751 TI - Striated muscle function, regeneration, and repair. AB - As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native skeletal and cardiac muscles, mechanisms underlying striated muscle dysfunction, and bioengineering strategies to treat muscle disorders. We focus on different sources for cellular therapy, biomaterials to augment the endogenous regenerative response, and progress in engineering and application of mature striated muscle tissues in vitro and in vivo. Finally, we discuss the challenges and perspectives in translating muscle bioengineering strategies to clinical practice. PMID- 27271759 TI - Airway Evaluation with Multidetector Computed Tomography Post-Processing Methods in Asthmatic Patients. AB - Asthma is a chronic inflammatory obstructive airways disease. The disease occurs regardless of age and manifests with cough, attacks of breathlessness, and tightness in the chest. The pathophysiology of asthma is complex and still not fully understood. It is essential to find answers concerning the role of each part of the bronchial tree in asthma, especially the role of small bronchioles. With the development of newer generations of multidetector computed tomography (MDCT) and advanced post-processing methods it is possible to obtain more detailed images and gain insight into further aspects of asthma. MDCT post processing methods can be divided into two-dimensional (2D) and three-dimensional (3D). In 2D projections, visualized hypodense regions correspond to the airway flow limitations. With the more advanced methods, such as multi planar reconstructions (MPR), images in different planes (axial, coronal, or sagittal) can be created. In the MPR technique only the voxels which are adjacent to each other in the predetermined plane can be extracted from the data set. Using the minimal/maximal intensity projections and shaded surface display, the volume of interest (VOI) can be extracted. High resolution CT scans can be used to create a more advanced imaging tool - the virtual bronchoscopy (VB). Using the VB makes it possible to visualize regions of obturation in the bronchi of up to the 5-8th generation. The MDCT with advanced post-processing methods is likely to assume an important role in the differential diagnosis of asthma, particularly when the diagnosis is dubious or hard to settle due to accompanying other lung diseases. PMID- 27271760 TI - Phosphate starvation promoted the accumulation of phenolic acids by inducing the key enzyme genes in Salvia miltiorrhiza hairy roots. AB - KEY MESSAGE: Phosphate starvation increased the production of phenolic acids by inducing the key enzyme genes in a positive feedback pathway in Saliva miltiorrhiza hairy roots. SPX may be involved in this process. Salvia miltiorrhiza is a wildly popular traditional Chinese medicine used for the treatment of coronary heart diseases and inflammation. Phosphate is an essential plant macronutrient that is often deficient, thereby limiting crop yield. In this study, we investigated the effects of phosphate concentration on the biomass and accumulation of phenolic acid in S. miltiorrhiza. Results show that 0.124 mM phosphate was favorable for plant growth. Moreover, 0.0124 mM phosphate was beneficial for the accumulation of phenolic acids, wherein the contents of danshensu, caffeic acid, rosmarinic acid, and salvianolic acid B were, respectively, 2.33-, 1.02-, 1.68-, and 2.17-fold higher than that of the control. By contrast, 12.4 mM phosphate inhibited the accumulation of phenolic acids. The key enzyme genes in the phenolic acid biosynthesis pathway were investigated to elucidate the mechanism of phosphate starvation-induced increase of phenolic acids. The results suggest that phosphate starvation induced the gene expression from the downstream pathway to the upstream pathway, i.e., a feedback phenomenon. In addition, phosphate starvation response gene SPX (SYG1, Pho81, and XPR1) was promoted by phosphate deficiency (0.0124 mM). We inferred that SPX responded to phosphate starvation, which then affected the expression of later responsive key enzyme genes in phenolic acid biosynthesis, resulting in the accumulation of phenolic acids. Our findings provide a resource-saving and environmental protection strategy to increase the yield of active substance in herbal preparations. The relationship between SPX and key enzyme genes and the role they play in phenolic acid biosynthesis during phosphate deficiency need further studies. PMID- 27271761 TI - Rescue effects of intravenous immunoglobulin on optic nerve degeneration in a rat model of neuromyelitis optica. AB - PURPOSE: Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that predominantly attacks the optic nerve and spinal cord. This study evaluated the effect of administration of human IgG (hIgG) into the caudal vein on optic nerve degeneration in a rodent model of NMO. METHODS: The optic nerves were exposed to AQP4-Ab-positive sera, and the administration of intravenous immunoglobulin (IVIG) was performed immediately, at 7 days (cohort A) or at 7 days and 10 days (cohort B) after exposure to the sera. A reference group, similarly exposed to the serum, was treated with saline. Retinal ganglion cells (RGCs) labeled by the injection of Fluoro-Gold into the superior colliculus were counted in whole mounted retina. RGCs labeled by the injection of Fluoro-Gold into the superior colliculus were counted in the whole-mounted retina. RESULTS: The number of RGCs 14 days after optic nerve exposure to sera from patients with NMO was 1455 +/- 192/mm(2) (n = 7) in cohort A, 1657 +/- 192/mm(2) (n = 4) in cohort B, and 981 +/ 182/mm(2) (n = 10) in the saline-treated reference group (p < 0.001). Western blotting revealed that the content of neurofilament in the optic nerve of the hIgG-treated group in cohort A was significantly greater than that in the reference group (p = 0.037). CONCLUSIONS: IVIG administration reduced optic nerve degeneration in a rat model of NMO-optic neuritis. IVIG could be used as a treatment in the acute phase of NMO. PMID- 27271762 TI - Changes in visual field defects during 10-year follow-up for indocyanine green assisted macular hole surgery. AB - PURPOSE: To determine whether the visual field defects detected within 3 months of indocyanine green (ICG)-assisted inner-limiting membrane (ILM) peeling continue to worsen over longer periods. METHODS: This was a retrospective observational case series. Four eyes with visual field defects that developed within 3 years of ICG-assisted ILM peeling for a macular hole (MH) were examined yearly for 10 years. The main outcome measures were the degree of mean deviation (MD) determined by Humphrey perimetry with the 30-2 SITA-Fast program and the best-corrected visual acuity (BCVA). RESULTS: Four patients were examined yearly for more than 10 years, with a mean duration of follow-up of 139.5 months (11.6 years) and a range of follow-up of 137-156 months (11.4-13 years). The mean (+/ standard deviation) preoperative MD value was -4.99 +/- 3.26 dB, and the mean postoperative MD values were -12.9 +/- 1.29 dB after 1 year, -14.1 +/- 0.75 dB after 3 years, and -12.73 +/- 2.65 dB after 10 years. The mean preoperative BCVA was 0.65 +/- 0.26 logarithm of the minimal angle of resolution (logMAR) units, and the postoperative BCVA was 0.21 +/- 0.07 logMAR units at 1 year, 0.28 +/- 0.21 logMAR units at 3 years, and 0.14 +/- 0.06 dB logMAR units at 10 years. CONCLUSIONS: The visual field defects detected soon after ICG-assisted ILM peeling continued to worsen for 3 years, but not thereafter. PMID- 27271763 TI - Comparison of keratometric measurements obtained by the Verion Image Guided System with optical biometry and auto-keratorefractometer. AB - The aim of this study was to compare the keratometric measurements of Verion Image Guided System with an optical biometer (Zeiss IOLMaster 500, Carl Zeiss Meditec, Jena, Germany) and an automated keratorefractometer (AKR) (Topcon KR 8900, Topcon, Japan). In this prospective clinical trial, the right eyes of 52 patients with cataract were examined (mean age 62.25 +/- 12.16 years). The measurements were taken by the three systems in a random order. Keratometric data, magnitude of astigmatism, and astigmatic axis measurements from all three instruments were compared. The results were evaluated using, intraclass correlation coefficients (ICC), Bland-Altman plots, and paired samples t tests. The mean flat/steep K of Verion, IOLMaster, and AKR were 43.22 +/- 1.38D/44.23 +/ 1.46D, 43.07 +/- 1.26D/44.05 +/- 1.34D, and 43.07 +/- 1.31D/43.89 +/- 1.42D, respectively. Flat K readings of Verion were higher than IOLMaster and AKR (p < 0.05 for both). Steep K readings were different for all three (p < 0.05). The magnitude of astigmatism by Verion and IOLMaster were 0.98 +/- 0.65D and 0.98 +/- 0.59D (p = 0.88). The mean astigmatism measured by the AKR was 0.82 +/- 0.62D, less than the other two instruments (p < 0.001). Astigmatic axis measurements of Verion and AKR differed <10 degrees in 38, between 10 degrees and 20 degrees in 5, and >20 degrees in 9 eyes; the same difference was 30, 11, and 11 eyes, respectively, between Verion and IOLMaster. Although, keratometric and astigmatic results obtained from Verion were not completely interchangeable with IOLMaster and AKR, especially the agreement between Verion and IOLMaster was excellent with ICCs close to one. However, there were pronounced astigmatic axis measurement differences between three instruments. PMID- 27271765 TI - Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis. AB - Few contemporary data are available that compare incidence and survival of metastatic breast cancer between ductal and lobular carcinomas. Using the Surveillance, Epidemiology, and End Results-9 registries, we identified 10,639 patients with de novo metastatic breast cancer diagnosed from 1990 to 2011. Annual age-adjusted incidence rates and annual percent changes (APCs) were analyzed. Multivariable Cox regression models were used to investigate the impact of year of diagnosis and histology on overall survival. 9250 (86.9 %) patients had ductal and 1389 (13.1 %) had lobular carcinomas. Metastatic breast cancer incidence increased slightly over time for ductal (APC = +1.7, 95 % confidence interval (CI) = +1.0 to +2.4) and lobular carcinomas (APC = +3.0, 95 % CI = +1.8 to +4.3). Median overall survival was 22 months among the whole cohort. More recent year of diagnosis was associated with better overall survival only for patients with ductal carcinomas (interaction p value = 0.006), with an adjusted hazard ratio of death for every five-year increment in the date of diagnosis of 0.93 (95 % CI = 0.91-0.95) among ductal carcinomas, compared with 1.05 (95 % CI = 0.95-1.10) among lobular carcinomas. Overall survival was longer for lobular versus ductal carcinomas (28 versus 21 months, respectively; adjusted hazard ratio of death = 0.93, 95 % CI = 0.87-0.99), but the magnitude of this effect was attenuated among the cohort restricted to hormone receptor-positive tumors. In this population-based analysis, incidence rates of metastatic breast cancer at presentation increased slightly over time for both histologies, and particularly for lobular tumors. A modest improvement in metastatic breast cancer median overall survival was observed, but was apparently limited to ductal carcinomas. PMID- 27271766 TI - Associations between metabolic syndrome, breast cancer recurrence, and the 21 gene recurrence score assay. AB - The 21-gene recurrence score (RS) assay is prognostic in estrogen receptor positive (HR+), HER2-negative, node-negative breast cancer (BC). The interaction between RS and host factors including metabolic syndrome (MS) is unclear. MS conditions such as obesity have been associated with worse BC prognosis. The aim of this study was to identify associations between presence of MS conditions and RS group or breast cancer recurrence. Demographic, pathologic, and treatment data, MS criteria, and menopausal status were abstracted from medical records of women with stage I-II, HR+, HER2-negative BC evaluated with the RS assay at a single institution since 2005. MS was defined as presence of >=3 of the following within 2 years of diagnosis: body mass index >=27.7 kg/m(2); hypertension; impaired fasting glucose; HDL <50 mg/dL; hypertriglyceridemia. Of 533 eligible women, 22 % had MS. MS was more common in post- vs premenopausal women (30 vs 9 %; P < 0.0001). There was no significant association between RS group and overall MS status or any individual criterion, controlling for stage, and no association after stratification by menopausal status. Postmenopausal status was associated with higher RS group (P = 0.039), independent of stage. With 4.2-year median follow-up, no association between disease recurrence and MS was identified. Although MS has been associated with worse BC outcomes, we were unable to identify associations between RS group and MS criteria. Identification of prognostic factors other than RS that underlie this higher risk will be important for optimizing breast cancer treatment decision-making in patients with MS. PMID- 27271768 TI - Interplay between Graph Topology and Correlations of Third Order in Spiking Neuronal Networks. AB - The study of processes evolving on networks has recently become a very popular research field, not only because of the rich mathematical theory that underpins it, but also because of its many possible applications, a number of them in the field of biology. Indeed, molecular signaling pathways, gene regulation, predator prey interactions and the communication between neurons in the brain can be seen as examples of networks with complex dynamics. The properties of such dynamics depend largely on the topology of the underlying network graph. In this work, we want to answer the following question: Knowing network connectivity, what can be said about the level of third-order correlations that will characterize the network dynamics? We consider a linear point process as a model for pulse-coded, or spiking activity in a neuronal network. Using recent results from theory of such processes, we study third-order correlations between spike trains in such a system and explain which features of the network graph (i.e. which topological motifs) are responsible for their emergence. Comparing two different models of network topology-random networks of Erdos-Renyi type and networks with highly interconnected hubs-we find that, in random networks, the average measure of third-order correlations does not depend on the local connectivity properties, but rather on global parameters, such as the connection probability. This, however, ceases to be the case in networks with a geometric out-degree distribution, where topological specificities have a strong impact on average correlations. PMID- 27271769 TI - Epinephrine auto-injector needle length: what is the ideal length? AB - PURPOSE OF REVIEW: The purpose of this manuscript is to review the literature on the clinical effects of the needle length of epinephrine (adrenaline) auto injectors. RECENT FINDINGS: Epinephrine has maximal pharmacodynamic effect within 10 min of intramuscular administration into the thigh. Prefilled epinephrine auto injectors are designed for simplicity of use and safety. Auto-injectors are primarily used by patients in an unsupervised setting in cases of anaphylaxis. There are weight-appropriate doses of epinephrine available with auto-injectors that are prefilled, to prevent dosing errors, with 0.15, 0.30, and 0.50 mg amounts. In addition, needle lengths vary from 1.17 to 2.50 cm. The recommended needle lengths differ between adults and pediatric patients. In addition, the needle lengths differ between devices as well. There are concerns that the needle length may be too short in select obese patients. Yet, there are also concerns that the needle length may be too long in some patients. Factors that affect the depth of the injection, and therefore the pharmacokinetics of the drug, include not only the needle length but also the BMI, obesity, compression of soft tissue, and propulsion. SUMMARY: Epinephrine auto-injectors have different needle lengths. Using the right device with appropriate needle length based on BMI, obesity, and employing the proper technique can improve the outcome in an anaphylactic event. PMID- 27271767 TI - Long-term cardiovascular outcomes and overall survival of early-stage breast cancer patients with early discontinuation of trastuzumab: a population-based study. AB - We critically examined long-term cardiovascular (CV) outcomes and overall survival (OS) of breast cancer (BC) patients who had cardiotoxicity during adjuvant trastuzumab treatment requiring discontinuation in a population-based sample. This was a retrospective cohort of early-stage BC patients diagnosed before 2010 and treated with trastuzumab in Ontario. Patients were stratified based on trastuzumab doses received: 1-8, 9-15, >=16 (therapy completion). Time dependent multivariable Cox models were used to analyze primary endpoint OS, and the following composite endpoints: hospitalization/emergency room visit for heart failure (HF) or death; non-HF CV (myocardial infarction, stroke) or death; and clinically significant relapse (palliative systemic therapy initiation >90 days after last trastuzumab dose) or death. Of the 3134 women, 6, 10, and 85 % received 1-8, 9-15, and >=16 doses, respectively. Over 5-year median follow-up, early trastuzumab discontinuation was associated with more HF/death [1-8 doses hazard ratio (HR) 4.0, 95 % confidence interval (CI) 2.7-6.0; 9-15 doses HR 2.97, 95 % CI 2.1-4.3], non-HF/death (1-8 doses HR 4.3, 95 % CI 3.0-6.1; 9-15 doses HR 3.1, 95 % CI 2.2-4.4), clinically significant relapse/death (1-8 doses HR 3.1, 95 % CI 2.2-4.4; 9-15 doses HR 2.4, 95 % CI 1.8-3.3), and importantly lower OS (77, 80, 93 %; P < 0.001). Early discontinuation (1-8 doses HR 2.41, 95 % CI 1.5-3.8; 9-15 doses HR 2.9, 95 % CI 2.0-4.1) and clinically significant relapse (HR 34.0, 95 % CI 24.9-46.6) were both independent predictors of mortality. Of note, early discontinuation remained a critical independent predictor of OS even after adjusting for incident HF. Early trastuzumab discontinuation is a powerful independent predictor of cardiac events and clinically significant relapse, and both may contribute to poor survival. Both adequate cancer control and optimal CV management are required to improve long-term outcomes. PMID- 27271770 TI - Interleukin-1beta induced Stress Granules Sequester COX-2 mRNA and Regulates its Stability and Translation in Human OA Chondrocytes. AB - Enhanced and immediate expression of cyclooxygenase-2 (COX-2) mRNA is observed in IL-1beta-stimulated OA chondrocytes but the synthesis of protein found significantly delayed. Here we investigated the role of stress granules (SGs), ribonucleoprotein complexes that regulate mRNA translation, in the delayed translation of COX-2 mRNAs in IL-1beta-stimulated OA chondrocytes. Stimulation of human chondrocytes with IL-1beta activated the stress response genes and the phosphorylation of eIF2alpha that triggered the assembly of SGs. Using combined immunofluorescence staining of SGs markers and COX-2 protein, RNA fluorescence in situ hybridization and RNA immunoprecipitation, the COX-2 mRNAs were found sequestered in SGs in IL-1beta-stimulated OA chondrocytes. No increase in COX-2 protein expression was observed during the persistence of SGs but enhanced expression of COX-2 protein was noted upon clearance of the SGs. Inhibition of SGs clearance blocked COX-2 mRNA translation whereas blocking the assembly of SGs by TIA-1 depletion resulted in rapid and increased production of COX-2 and PGE2. Our findings show for the first time assembly of SGs and sequestration of COX-2 mRNAs in human OA chondrocytes under pathological conditions. Post transcriptional regulation of COX-2 mRNAs translation by SGs indicates a role in IL-1beta-mediated catabolic response that could be therapeutically targeted in OA. PMID- 27271771 TI - A Raloxifene Withdrawal Response: Translational Research, Definitions, and Clinical Applications. PMID- 27271772 TI - High resolution, week-long, locomotion time series from Japanese quail in a home box environment. AB - Temporal and spatial patterns of locomotion reflect both resting periods and the movement from one place to another to satisfy physiological and behavioural needs. Locomotion is studied in diverse areas of biology such as chronobiology and physiology, as well as in biomathematics. Herein, the locomotion of 24 visually-isolated Japanese quails in their home-box environment was recorded continuously over a 6.5 days at a 0.5 s sampling rate. Three time series are presented for each bird: (1) locomotor activity, (2) distance ambulated, and (3) zone of the box where the bird is located. These high resolution, week-long, time series consisting of 1.07*10(6) data points represent, to our knowledge, a unique data set in animal behavior, and are publically available on FigShare. The data obtained can be used for analyzing dynamic changes of daily or several day locomotion patterns, or for comparison with existing or future data sets or mathematical models across different taxa. PMID- 27271773 TI - Mild and Low-Pressure fac-Ir(ppy)3 -Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis. AB - A novel, mild and facile preparation of alkyl amides from unactivated alkyl iodides employing a fac-Ir(ppy)3 -catalyzed radical aminocarbonylation protocol has been developed. Using a two-chambered system, alkyl iodides, fac-Ir(ppy)3 , amines, reductants, and CO gas (released ex situ from Mo(CO)6 ), were combined and subjected to an initial radical reductive dehalogenation generating alkyl radicals, and a subsequent aminocarbonylation with amines affording a wide range of alkyl amides in moderate to excellent yields. PMID- 27271774 TI - Age-based discrimination of rival males in western bluebirds. AB - Adaptive social behavior frequently involves discriminating between classes of individuals such as relatives versus non-relatives, older versus younger individuals, or individuals of different status. In the absence of spatial cues, this discrimination may be based on signals that correlate with fitness-related traits (e.g., older or high-status males may sing higher performance songs) or with identity, for example, when receivers distinguish and classify signalers based on their unique signal structure. Here, we examine vocal age-based discrimination in western bluebirds (Sialia mexicana), a North American songbird in which older males have a significant advantage in obtaining extra-pair fertilizations, and therefore pose a significantly higher threat to paternity than younger males. We asked whether western bluebird males showed a higher response to playback of songs of older males compared to younger males relative to their own age. We prepared song stimuli by removing three potential signals of age that have been identified as important in other species: (1) note consistency (which was achieved by playing a single instance of each note repeatedly), (2) note repertoire size, and (3) singing rate (the latter two were equalized across conditions). Even in the absence of these potential signals of age, young males responded more strongly to playback of older males' songs than to young males' songs, suggesting that they are able to discriminate between age classes relative to the threat they pose. Further research is required to determine whether this discrimination is based on individual recognition or signal features that are correlated with age. PMID- 27271775 TI - Effect of target animacy on hand preference in Sichuan snub-nosed monkeys (Rhinopithecus roxellana). AB - Twenty-eight captive Sichuan snub-nosed monkeys (Rhinopithecus roxellana) were involved in the current study. Many individuals showed handedness, with a modest tendency toward left-hand use especially for animate targets, although no group level handedness was found. There was no significant gender difference in the direction and strength of hand preference for both targets. Females showed a significantly higher overall rate of actions toward animate targets than inanimate targets for both hands, whereas males displayed almost the reversed pattern. There were no significant interactions between lateral hand use and target animacy for either males or females. Most individuals showed rightward or leftward laterality shift trends between inanimate and animate targets. These findings to some extent support the existence of a potential trend concerning a categorical neural distinction between targets demanding functional manipulation (inanimate objects) and those demanding social manipulation (animate objects), even though specialized hand preference based on target animacy has not been fully established in this arboreal Old World monkey species. PMID- 27271776 TI - Aberrant Expression of Anaplastic Lymphoma Kinase in Ovarian Carcinoma Independent of Gene Rearrangement. AB - Ovarian carcinoma is the leading cause of death from gynecologic malignancies. The oncogenic role of anaplastic lymphoma kinase (ALK) is well characterized in many hematopoietic and solid tumors. ALK expression in ovarian carcinoma has been reported but the exact status of ALK protein and its association with clinicopathologic features requires further investigation. ALK expression was determined by immunohistochemistry in 110 primary ovarian carcinomas, including 85 cases of serous carcinoma and 25 cases of mucinous carcinoma. Fluorescence in situ hybridization (FISH) and real-time reverse transcription polymerase chain reaction (RT-PCR) were used for evaluating ALK translocation in ALK-positive ovarian carcinomas. Among 110 ovarian carcinomas, 23 (20.9%) cases were ALK positive by immunohistochemistry. All ALK-positive cases were ovarian high-grade serous carcinoma. ALK expression was detected in 23/85 (27.1%) ovarian serous carcinoma and 0/25 (0%) in ovarian mucinous carcinoma. None of the 23 ALK IHC positive cases harbored ALK gene translocations by FISH or RT-PCR. ALK protein expression was associated with patient age, tumor stage, and histologic type. Specifically, the probability of ALK protein expression was significantly higher in high-grade serous carcinomas in older patients (above 50 y) with advanced disease (FIGO stage III and IV) compared with the low-grade serous and mucinous carcinomas in younger patients with relatively early disease. In conclusion, aberrant ALK expression is observed in ovarian serous carcinoma but not in mucinous carcinoma, is independent of gene translocation, and might be associated with progression and prognosis. PMID- 27271777 TI - When the Perpetrator Is a Partner: Arrest and Charging Decisions in Intimate Partner Sexual Assault Cases-A Focal Concerns Analysis. AB - Law enforcement officials and prosecutors have been called "gatekeepers" of the criminal justice system, as their discretionary decisions determine case outcomes. Using the focal concerns perspective as our theoretical foundation, we explore the factors that influence arrest and charging decisions in intimate partner sexual assaults (IPSA) reported to Los Angeles law enforcement in 2008. Quantitative findings are supplemented with qualitative examples from Los Angeles Police Department (LAPD) detectives interviewed in 2010 and charge evaluation sheets from complaints referred to Los Angeles prosecution in 2008. Attempting to expand its theoretical relevance, we develop an alternative conceptualization and operationalization of the focal concerns perspective that is more appropriate to IPSA cases. Findings suggest that arrest decisions are motivated by suspect blameworthiness, community protection, and practical constraints and organizational consequences. In addition, charging decisions are influenced by community protection and practical constraints. Extralegal factors did not influence decision making. Directions for future research are discussed. PMID- 27271778 TI - The Researcher-Practitioner Partnership Study (RPPS): Experiences From Criminal Justice System Collaborations Studying Violence Against Women. AB - The benefits of researcher-practitioner (R-P) collaborations focused on violence against women (VAW) are many. Such projects support researchers and practitioners working together to create uniquely comprehensive projects that have the potential to change practices, policies, and services. Extant literature is limited in that it has (a) focused on the experiences of a very limited number of collaborations, (b) ignored collaborations conducted in the context of the criminal justice system, and (c) excluded as a focus the products that result from the collaborations and their dissemination. Therefore, the goal of this qualitative study is to identify the essential elements to consider for successful R-P collaborations on VAW research in the criminal justice system. PMID- 27271779 TI - "I Wasn't a Priority, I Wasn't a Victim": Challenges in Help Seeking for Transgender Survivors of Intimate Partner Violence. AB - Among the crucial advancements in the study of intimate partner violence (IPV) is an understanding of the distinct help-seeking barriers that gay and lesbian victims face. Despite these additions to the literature, transgender IPV victimization remains under-researched. The current study utilized semi structured interviews and open-ended questionnaires of 18 trans-identified survivors of IPV. Working through a modified grounded analytic approach, two major themes emerged in the help-seeking process: "walking the gender tightrope" in which participants first struggled with gendered notions of victimization that made it difficult to identify abuse, and second, the challenges of "navigating genderist resources." PMID- 27271780 TI - Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites. AB - BACKGROUND: We have previously shown that meal ingestion induces cognitive perception (sensations) with a hedonic dimension (well-being) that depends on the characteristics of the meal and the appropriateness of the digestive response. The aim of the present study is to identify metabolomic biomarkers of the cognitive response to meal ingestion. METHODS: In 18 healthy subjects, the response to a test meal (Edanec, 1 kcal/mL) ingested until maximum satiation (50 mL/min) was assessed. Perception measurements and blood samples were taken before, at the end of the meal, and 20 min after ingestion. The cognitive response and the hedonic dimension were measured on 10 cm scales. Metabolomic analysis was performed using nuclear magnetic resonance (NMR) spectroscopy and values of triglycerides, insulin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were determined using conventional laboratory techniques. KEY RESULTS: Ingestion up to maximum satiation induced sensation of fullness and decreased digestive well-being. The total amount ingested by each subject correlated with the basal sensation of hunger, but not with other sensations or blood metabolite levels. Immediately after ingestion, satiation correlated with an increase in glucose (R = 0.49; p = 0.038) and valine levels (R = 0.48; p = 0.043). Twenty minutes after finalizing ingestion, triglyceride levels had significantly increased which correlated with the recovery in well-being (R = 0.48; p = 0.046) and the decrease in desire to eat a food of choice (R = -0.56; p = 0.016). The increase in lipids inversely correlated with abdominal discomfort (R = -0.51; p = 0.032). CONCLUSIONS & INFERENCES: Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites, which may serve as objective biomarkers of perception. PMID- 27271781 TI - Genome-Assisted Prediction of Quantitative Traits Using the R Package sommer. AB - Most traits of agronomic importance are quantitative in nature, and genetic markers have been used for decades to dissect such traits. Recently, genomic selection has earned attention as next generation sequencing technologies became feasible for major and minor crops. Mixed models have become a key tool for fitting genomic selection models, but most current genomic selection software can only include a single variance component other than the error, making hybrid prediction using additive, dominance and epistatic effects unfeasible for species displaying heterotic effects. Moreover, Likelihood-based software for fitting mixed models with multiple random effects that allows the user to specify the variance-covariance structure of random effects has not been fully exploited. A new open-source R package called sommer is presented to facilitate the use of mixed models for genomic selection and hybrid prediction purposes using more than one variance component and allowing specification of covariance structures. The use of sommer for genomic prediction is demonstrated through several examples using maize and wheat genotypic and phenotypic data. At its core, the program contains three algorithms for estimating variance components: Average information (AI), Expectation-Maximization (EM) and Efficient Mixed Model Association (EMMA). Kernels for calculating the additive, dominance and epistatic relationship matrices are included, along with other useful functions for genomic analysis. Results from sommer were comparable to other software, but the analysis was faster than Bayesian counterparts in the magnitude of hours to days. In addition, ability to deal with missing data, combined with greater flexibility and speed than other REML-based software was achieved by putting together some of the most efficient algorithms to fit models in a gentle environment such as R. PMID- 27271783 TI - Differences in Child Passenger Safety Counseling Frequency and Attitudes by Health Care Provider Specialty. AB - Many children are not being properly restrained in motor vehicles, resulting in unnecessary injury and fatalities. Health care provider (HCP) education is effective at increasing proper child restraint within vehicles. However, differences exist by HCP specialty in regards to frequency of child passenger safety (CPS) counseling. This study of a sample of 255 HCPs examined differences in CPS counseling by HCP specialty (pediatric vs. non-pediatric). HCPs from several upper Midwest states were surveyed about how frequently they provide CPS counseling in their practice by patient age and their attitudes toward CPS related issues. Pediatric HCPs were twice as likely as non-pediatric HCPs to always provide CPS counseling to parents/guardians of children aged 5 or older. Non-pediatric HCPs were more likely than pediatric HCPs to feel that counseling is ineffective at increasing child seat/booster (p = 0.001) or seat belt use (p = 0.006). Non-pediatric HCPs were more likely than pediatric HCPs to feel there is inadequate time to provide CPS counseling in their practice setting (p = 0.001), and were less likely to know where to refer patients if they have questions regarding CPS issues (0.0291). The differences in HCP attitudes toward CPS counseling provision and the resulting differences in counseling frequency by patient age may contribute to disparities for patients who have limited or no access to pediatric HCPs. Additional research is needed to investigate the rationale for counseling differences seen by HCP specialty and patient age, and the potential effect on child motor vehicle injuries and fatalities. PMID- 27271784 TI - Attitudes towards poverty, organizations, ethics and morals: Israeli social workers' shared decision making. AB - OBJECTIVE: Partnerships between service users and social workers are complex in nature and can be driven by both personal and contextual circumstances. This study sought to explore the relationship between social workers' involvement in shared decision making with service users, their attitudes towards service users in poverty, moral standards and health and social care organizations' policies towards shared decision making. METHODS: Based on the responses of 225 licensed social workers from health and social care agencies in the public, private and third sectors in Israel, path analysis was used to test a hypothesized model. RESULTS: Structural attributions for poverty contributed to attitudes towards people who live in poverty, which led to shared decision making. Also, organizational support in shared decision making, and professional moral identity, contributed to ethical behaviour which led to shared decision making. CONCLUSION: The results of this analysis revealed that shared decision making may be a scion of branched roots planted in the relationship between ethics, organizations and Stigma. PMID- 27271786 TI - Using degrees of rate control to improve selective n-butane oxidation over model MOF-encapsulated catalysts: sterically-constrained Ag3Pd(111). AB - Metal nanoparticles encapsulated within metal organic frameworks (MOFs) offer steric restrictions near the catalytic metal that can improve selectivity, much like in enzymes. A microkinetic model is developed for the regio-selective oxidation of n-butane to 1-butanol with O2 over a model for MOF-encapsulated bimetallic nanoparticles. The model consists of a Ag3Pd(111) surface decorated with a 2-atom-thick ring of (immobile) helium atoms which creates an artificial pore of similar size to that in common MOFs, which sterically constrains the adsorbed reaction intermediates. The kinetic parameters are based on energies calculated using density functional theory (DFT). The microkinetic model was analysed at 423 K to determine the dominant pathways and which species (adsorbed intermediates and transition states in the reaction mechanism) have energies that most sensitively affect the reaction rates to the different products, using degree-of-rate-control (DRC) analysis. This analysis revealed that activation of the C-H bond is assisted by adsorbed oxygen atoms, O*. Unfortunately, O* also abstracts H from adsorbed 1-butanol and butoxy as well, leading to butanal as the only significant product. This suggested to (1) add water to produce more OH*, thus inhibiting these undesired steps which produce OH*, and (2) eliminate most of the O2 pressure to reduce the O* coverage, thus also inhibiting these steps. Combined with increasing butane pressure, this dramatically improved the 1 butanol selectivity (from 0 to 95%) and the rate (to 2 molecules per site per s). Moreover, 40% less O2 was consumed per oxygen atom in the products. Under these conditions, a terminal H in butane is directly eliminated to the Pd site, and the resulting adsorbed butyl combines with OH* to give the desired 1-butanol. These results demonstrate that DRC analysis provides a powerful approach for optimizing catalytic process conditions, and that highly selectivity oxidation can sometimes be achieved by using a mixture of O2 and H2O as the oxidant. This was further demonstrated by DRC analysis of a second microkinetic model based on a related but hypothetical catalyst, where the activation energies for two of the steps were modified. PMID- 27271785 TI - Association of Cerebral Microbleeds With Cognitive Decline and Dementia. AB - IMPORTANCE: Cerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear. OBJECTIVE: To determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population. DESIGN, SETTING, AND PARTICIPANTS: The Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards. EXPOSURES: Cerebral microbleed presence, location, and number. MAIN OUTCOMES AND MEASURES: Cognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15 word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia. RESULTS: In total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference in z score, -0.44; 95% CI, -0.65 to -0.22; P < .001), and memory function (mean difference in z score, -0.34; 95% CI, -0.64 to -0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, -0.61; 95% CI, -1.05 to -0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64). CONCLUSIONS AND RELEVANCE: In the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage. PMID- 27271787 TI - Is one diagnosis the whole story? patients with double diagnoses. AB - One of the goals of evaluating a patient in the genetics clinic is to find the diagnosis that would explain his or her clinical presentation. Sometimes the patient's diagnosis remains undefined or does not explain all of the clinical findings. As clinicians are often guided by a "single disorder" paradigm, diagnosing multiple genetic conditions in the same patient requires a heightened sense of awareness. Over the last few years, we evaluated several patients (n = 14) who were found to have more than one genetic diagnosis. In this paper, we will describe their natural history and diagnoses, and draw on the lessons learned from this phenomenon, which we expect to grow in this era of next generation diagnostic technologies. To our knowledge, this is by far the largest series of patients with double diagnoses. Based on our findings, we strongly recommend that physicians question every diagnosis to determine whether it indeed explains all of the patients' symptoms, and consider whether they should continue the diagnostic evaluation to look for a more accurate and complete set of diagnoses. (c) 2016 Wiley Periodicals, Inc. PMID- 27271788 TI - The care needs and experiences with the use of services of people with young onset dementia and their caregivers: a systematic review. AB - OBJECTIVE: In this review, the care needs and experiences with the use of available services of individuals with young-onset dementia (YOD) and their caregivers were investigated. This knowledge is an important prerequisite for the development of appropriate interventions and personalized care to address their specific needs and problems. DESIGN: A systematic literature search was performed in PubMed, Psycinfo and Cinahl. A quality checklist for observational and qualitative studies was used to appraise the methodological quality of the studies. RESULTS: Twenty-seven studies were included, and a synthesis of the literature revealed six themes. The first theme concerned problems in the diagnostic period. Early recognition and referral was reported as an essential area that required improvement in order to obtain appropriate help in time. The second theme discussed the need for information about YOD and the availability of care throughout the caregiving trajectory. The third theme described barriers in access to care that hindered caregivers in finding the right services. The fourth theme showed the availability of appropriate services and specific unmet needs. The fifth theme illustrated that behavioural and personality changes pose a significant challenge for caregivers and other family members. The last theme showed the profound impact of YOD on caregivers. CONCLUSIONS: The literature indicates that people with YOD and their caregivers face a wide range of difficulties during the disease process. The reviewed studies provide an important foundation for knowledge and awareness about the specific care needs and experiences of people with YOD and their caregivers. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271789 TI - Paracetamol for low back pain. AB - BACKGROUND: Analgesic medication is the most frequently prescribed treatment for low back pain (LBP), of which paracetamol (acetaminophen) is recommended as the first choice medication. However, there is uncertainty about the efficacy of paracetamol for LBP. OBJECTIVES: To investigate the efficacy and safety of paracetamol for non-specific LBP. SEARCH METHODS: We conducted searches on the Cochrane Central Register of Controlled Trials (CENTRAL, which includes the Back and Neck Review Group trials register), MEDLINE, EMBASE, CINAHL, AMED, Web of Science, LILACS, and IPA from their inception to 7 August 2015. We also searched the reference lists of eligible papers and trial registry websites (WHO ICTRP and ClinicalTrials.gov). SELECTION CRITERIA: We only considered randomised trials comparing the efficacy of paracetamol with placebo for non-specific LBP. The primary outcomes were pain and disability. We also investigated quality of life, function, adverse effects, global impression of recovery, sleep quality, patient adherence, and use of rescue medication as secondary outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently performed the data extraction and assessed risk of bias in the included studies. We also evaluated the quality of evidence using the GRADE approach. We converted scales for pain intensity to a common 0 to 100 scale. We quantified treatment effects using mean difference for continuous outcomes and risk ratios for dichotomous outcomes. We used effect sizes and 95% confidence intervals as a measure of treatment effect for the primary outcomes. When the treatment effects were smaller than 9 points on a 0 to 100 scale, we considered the effect as small and not clinically important. MAIN RESULTS: Our searches retrieved 4449 records, of which three trials were included in the review (n = 1825 participants), and two trials were included in the meta analysis. For acute LBP, there is high-quality evidence for no difference between paracetamol (4 g per day) and placebo at 1 week (immediate term), 2 weeks, 4 weeks, and 12 weeks (short term) for the primary outcomes. There is high-quality evidence that paracetamol has no effect on quality of life, function, global impression of recovery, and sleep quality for all included time periods. There were also no significant differences between paracetamol and placebo for adverse events, patient adherence, or use of rescue medication. For chronic LBP, there is very low-quality evidence (based on a trial that has been retracted) for no effect of paracetamol (1 g single intravenous dose) on immediate pain reduction. Finally, no trials were identified evaluating patients with subacute LBP. AUTHORS' CONCLUSIONS: We found that paracetamol does not produce better outcomes than placebo for people with acute LBP, and it is uncertain if it has any effect on chronic LBP. PMID- 27271790 TI - Diagnosis and treatment of microscopic colitis. AB - Microscopic colitis (MC) designates two types of chronic diarrhea diseases, which are lymphocytic colitis and collagenous colitis. The prevalence of microscopic colitis is increasing in both Western and Eastern countries, possibly due to the high incidence of colonoscopic survey in chronic diarrhea patients. Although the overall prognosis of MC patients is mostly good, it should be noted that appropriate diagnosis and choice of treatment is required to assure a good clinical outcome for MC patients. Also, a certain population of MC patients may take a severe and refractory clinical course, and thus require advanced clinical care using medications supported by less evidence. In this review, we would like to feature the essential points regarding the diagnosis of MC, and also describe the current standard of treatments for MC patients. In addition, we would like to add some findings from the national survey and research carried out in Japan, to compare those data with the western countries. PMID- 27271791 TI - Response surface methodology applied to the generation of casein hydrolysates with antioxidant and dipeptidyl peptidase IV inhibitory properties. AB - BACKGROUND: Hydrolysis parameters affecting the release of dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant peptides from milk proteins have not been extensively studied. Therefore, a multifactorial (i.e. pH, temperature and hydrolysis time) composite design was used to optimise the release of bioactive peptides (BAPs) with DPP-IV inhibitory and antioxidant [oxygen radical absorbance capacity (ORAC)] properties from sodium caseinate. RESULTS: Fifteen sodium caseinate hydrolysates (H1-H15) were generated with ProtamexTM , a bacillus proteinase activity. Hydrolysis time (1 to 5 h) had the highest influence on both DPP-IV inhibitory properties and ORAC activity (P < 0.05). Alteration of incubation temperature (40 to 60 degrees C) and pH (6.5 to 8.0) had an effect on the DPP-IV inhibitory properties but not the ORAC activity of the Protamex sodium caseinate hydrolysates. A multi-functional hydrolysate, H12, was identified having DPP-IV inhibitory (actual: 0.82 +/- 0.24 vs. predicted optimum: 0.68 mg mL 1 ) and ORAC (actual: 639 +/- 66 vs. predicted optimum: 639 umol TE g-1 ) activity of the same order (P > 0.05) as the response surface methodology (RSM) predicted optimum bioactivities. CONCLUSION: Generation of milk protein hydrolysates through multifactorial design approaches may aid in the optimal enzymatic release of BAPs with serum glucose lowering and antioxidant properties. (c) 2016 Society of Chemical Industry. PMID- 27271792 TI - Real-time device-scale imaging of conducting filament dynamics in resistive switching materials. AB - ReRAM is a compelling candidate for next-generation non-volatile memory owing to its various advantages. However, fluctuation of operation parameters are critical weakness occurring failures in 'reading' and 'writing' operations. To enhance the stability, it is important to understand the mechanism of the devices. Although numerous studies have been conducted using AFM or TEM, the understanding of the device operation is still limited due to the destructive nature and/or limited imaging range of the previous methods. Here, we propose a new hybrid device composed of ReRAM and LED enabling us to monitor the conducting filament (CF) configuration on the device scale during resistive switching. We directly observe the change in CF configuration across the whole device area through light emission from our hybrid device. In contrast to former studies, we found that minor CFs were formed earlier than major CF contributing to the resistive switching. Moreover, we investigated the substitution of a stressed major CF with a fresh minor CF when large fluctuation of operation voltage appeared after more than 50 times of resistive switching in atmospheric condition. Our results present an advancement in the understanding of ReRAM operation mechanism, and a step toward stabilizing the fluctuations in ReRAM switching parameters. PMID- 27271793 TI - Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-kappaB/GR signaling pathways in combined radiation and burn injury in rats. AB - The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) alpha polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) kappaB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-alpha, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-kappaB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-alpha level, which may have contributed to the inactivation of p65NF-kappaB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-alpha or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-kappaB/GR signaling pathways. PMID- 27271795 TI - Characterization of fibroblast-free CWR-R1ca castration-recurrent prostate cancer cell line. AB - BACKGROUND: The previously established CWR-R1 cell line has been used as an in vitro model representing castration-recurrent prostate cancer. Microscopic observation of subconfluent cells demonstrated two distinct cellular morphologies: polygonal closely aggregated epithelial cells surrounded by bipolar fibroblastic cells with long processes. This study sought to establish and characterize a fibroblast-free derivative of the CWR-R1 cell line. METHODS: The CWR-R1ca cell line was established from CWR-R1 cells by removing fibroblasts using multiple cycles of short-term trypsinization, cloning, and pooling single cell colonies. Authentication of fibroblast-free CWR-R1ca cells was demonstrated by analyzing the expression of cytodifferentiation and prostate-associated markers, DNA and cytogenetic profiling, and growth pattern in the absence or presence of androgen. RESULTS: CWR-R1ca is an androgen-sensitive cell line that expresses the androgen receptor (AR) and its splice variant 7 and the luminal epithelia markers, CK-8, CK-18, and c-Met. CWR-R1fb fibroblasts isolated from CWR R1 cells express AR, hepatocyte growth factor-alpha, and mouse beta-actin but not AR-V7 or epithelial markers. Cytogenetic analysis of CWR-R1ca cells revealed a hyperdiploid male with numerical gains in chromosomes 1, 7, 8, 10, 11, and 12, deletion of one chromosome 2 allele, structural abnormalities that include der(1)t(1:4), der(4)t(2:4), der(10)t(4:10), and an unbalanced reciprocal translocation between chromosome 6 and 14. DNA-profiling revealed that CWR-R1ca cells had significant short-tandem repeat marker homology with CWR22Pc and CWR22Rv1 cell lines, which indicated lineage derivation from CWR22 prostate cancer xenografts. CWR-R1ca cells were responsive to the growth stimulatory effects of dihydrotestosterone (DHT) in the femtomolar range. CONCLUSION: This study establishes CWR-R1ca cells as a fibroblast-free derivative of the castration-recurrent CWR-R1 cell line. Prostate 76:1067-1077, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27271796 TI - Appropriate selection of dose coefficients in radiological assessments: C-14 and Cl-36: response to the letter of G Smith and M Thorne (2015 J. Radiol. Prot. 35 737-40). PMID- 27271794 TI - Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification. AB - ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane. PMID- 27271798 TI - Cell polarity reversal in ovarian low-grade serous carcinomas and micropapillary serous borderline tumours: immunohistochemical observations. PMID- 27271797 TI - Stereospecific Effects of Oxygen-to-Sulfur Substitution in DNA Phosphate on Ion Pair Dynamics and Protein-DNA Affinity. AB - Oxygen-to-sulfur substitutions in DNA phosphate often enhance affinity for DNA binding proteins. Our previous studies have suggested that this effect of sulfur substitution of both OP1 and OP2 atoms is due to an entropic gain associated with enhanced ion pair dynamics. In this work, we studied stereospecific effects of single sulfur substitution of either the OP1 or OP2 atom in DNA phosphate at the Lys57 interaction site of the Antennapedia homeodomain-DNA complex. Using crystallography, we obtained structural information on the RP and SP diastereomers of the phosphoromonothioate and their interaction with Lys57. Using fluorescence-based assays, we found significant affinity enhancement upon sulfur substitution of the OP2 atom. Using NMR spectroscopy, we found significant mobilization of the Lys57 side-chain NH3 (+) group upon sulfur substitution of the OP2 atom. These data provide further mechanistic insights into the affinity enhancement by oxygen-to-sulfur substitution in DNA phosphate. PMID- 27271799 TI - Generative rules of Drosophila locomotor behavior as a candidate homology across phyla. AB - The discovery of shared behavioral processes across phyla is a significant step in the establishment of a comparative study of behavior. We use immobility as an origin and reference for the measurement of fly locomotor behavior; speed, walking direction and trunk orientation as the degrees of freedom shaping this behavior; and cocaine as the parameter inducing progressive transitions in and out of immobility. We characterize and quantify the generative rules that shape Drosophila locomotor behavior, bringing about a gradual buildup of kinematic degrees of freedom during the transition from immobility to normal behavior, and the opposite narrowing down into immobility. Transitions into immobility unfold via sequential enhancement and then elimination of translation, curvature and finally rotation. Transitions out of immobility unfold by progressive addition of these degrees of freedom in the opposite order. The same generative rules have been found in vertebrate locomotor behavior in several contexts (pharmacological manipulations, ontogeny, social interactions) involving transitions in-and-out of immobility. Recent claims for deep homology between arthropod central complex and vertebrate basal ganglia provide an opportunity to examine whether the rules we report also share common descent. Our approach prompts the discovery of behavioral homologies, contributing to the elusive problem of behavioral evolution. PMID- 27271800 TI - A proton therapy system in Nagoya Proton Therapy Center. AB - The purpose of this paper is to describe an outline of a proton therapy system in Nagoya Proton Therapy Center (NPTC). The NPTC has a synchrotron with a linac injector and three treatment rooms: two rooms are equipped with a gantry and the other one is equipped with a fixed horizontal beamline. One gantry treatment room has a pencil beam scanning treatment delivery nozzle. The other two treatment rooms have a passive scattering treatment delivery nozzle. In the scanning treatment delivery nozzle, an energy absorber and an aperture system to treat head and neck cancer have been equipped. In the passive treatment delivery nozzle, a multi-leaf collimator is equipped. We employ respiratory gating to treat lung and liver cancers for passive irradiation. The proton therapy system passed all acceptance tests. The first patient was treated on February 25, 2013, using passive scattering fixed beams. Respiratory gating is commonly used to treat lung and liver cancers in the passive scattering system. The MLCs are our first choice to limit the irradiation field. The use of the aperture for scanning irradiation reduced the lateral fall off by half or less. The energy absorber and aperture system in scanning delivery is beneficial to treat head and neck cancer. PMID- 27271801 TI - Structural and biochemical characterization of the cell fate determining nucleotidyltransferase fold protein MAB21L1. AB - The exceptionally conserved metazoan MAB21 proteins are implicated in cell fate decisions and share considerable sequence homology with the cyclic GMP-AMP synthase. cGAS is the major innate immune sensor for cytosolic DNA and produces the second messenger 2'-5', 3'-5' cyclic GMP-AMP. Little is known about the structure and biochemical function of other proteins of the cGAS-MAB21 subfamily, such as MAB21L1, MAB21L2 and MAB21L3. We have determined the crystal structure of human full-length MAB21L1. Our analysis reveals high structural conservation between MAB21L1 and cGAS but also uncovers important differences. Although monomeric in solution, MAB21L1 forms a highly symmetric double-pentameric oligomer in the crystal, raising the possibility that oligomerization could be a feature of MAB21L1. In the crystal, MAB21L1 is in an inactive conformation requiring a conformational change - similar to cGAS - to develop any nucleotidyltransferase activity. Co-crystallization with NTP identified a putative ligand binding site of MAB21 proteins that corresponds to the DNA binding site of cGAS. Finally, we offer a structure-based explanation for the effects of MAB21L2 mutations in patients with eye malformations. The underlying residues participate in fold-stabilizing interaction networks and mutations destabilize the protein. In summary, we provide a first structural framework for MAB21 proteins. PMID- 27271802 TI - Intrusion Detection System Using Deep Neural Network for In-Vehicle Network Security. AB - A novel intrusion detection system (IDS) using a deep neural network (DNN) is proposed to enhance the security of in-vehicular network. The parameters building the DNN structure are trained with probability-based feature vectors that are extracted from the in-vehicular network packets. For a given packet, the DNN provides the probability of each class discriminating normal and attack packets, and, thus the sensor can identify any malicious attack to the vehicle. As compared to the traditional artificial neural network applied to the IDS, the proposed technique adopts recent advances in deep learning studies such as initializing the parameters through the unsupervised pre-training of deep belief networks (DBN), therefore improving the detection accuracy. It is demonstrated with experimental results that the proposed technique can provide a real-time response to the attack with a significantly improved detection ratio in controller area network (CAN) bus. PMID- 27271804 TI - Using data redundancy gained by patch overlaps to reduce truncation artifacts in magnetic particle imaging. AB - The imaging technology magnetic particle imaging allows the detection of magnetic material, in particular superparamagnetic nanoparticles, by remagnetization of the material via magnetic fields. The application is aimed at medical imaging where the particles are applied as tracer directly into the blood stream. Medical safety considerations such as peripheral nerve stimulation limit the maximal amplitude of the magnetic fields and in turn the field of view size. To handle this constraint the concept of patches was introduced, which allows a shift of a field of view to different positions in order to enlarge the imaging area. If this is done statically an overlap of patches can be used to reduce truncation artifacts occurring at the adjacent edges. In this contribution, a differentiation of two different kinds of patch overlaps, i.e. a trajectory and a system matrix overlap, is made. Further, different concepts to combine the resulting redundant information are investigated with respect to the reduction of truncation artifacts. The methods are analyzed in detail in a simulation study and validated on experimental data. PMID- 27271803 TI - Comparative Effect of Quercetin and Quercetin-3-O-beta-d-Glucoside on Fibrin Polymers, Blood Clots, and in Rodent Models. AB - The present study evaluates the in vitro, in vivo, and ex vivo antithrombotic and anticoagulant effect of two flavonoids: quercetin and quercetin-3-O-beta-d glucoside (isoquercetin). The present results have shown that quercetin and isoquercetin inhibit the enzymatic activity of thrombin and FXa and suppress fibrin clot formation and blood clotting. The prolongation effect of quercetin and isoquercetin against epinephrine and collagen-induced platelet activation may have been caused by intervention in intracellular signaling pathways including coagulation cascade and aggregation response on platelets and blood. The in vivo and ex vivo anticoagulant efficacy of quercetin and isoquercetin was evaluated in thrombin-induced acute thromboembolism model and in ICR mice. Our findings showed that in vitro and in vivo inhibitory effects of quercetin were slightly higher than that of quercetin glucoside, whereas in vitro and ex vivo anticoagulant effects of quercetin were weaker than that of quercetin glucoside because of their structural characteristics. PMID- 27271806 TI - System gamma as a function of image- and monitor-dynamic range. AB - System gamma is the end-to-end exponent that describes the relationship between the relative luminance values at capture and the reproduced image. The system gamma preferred by subjects is known to vary with the background luminance condition and the image in question. We confirm the previous two findings using an image database with both high and low dynamic range images (from 102 to 107), but also find that the preferred system gamma varies with the dynamic range of the monitor (CRT, LCD, or OLED). We find that the preferred system gamma can be predicted in all conditions and for all images by a simple model that searches for the value that best flattens the lightness distribution, where lightness is modeled as a power law of onscreen luminance. To account for the data, the exponent must vary with the viewing conditions. The method presented allows the inference of lightness perception in natural scenes without direct measurement and makes testable predictions for how lightness perception varies with the viewing condition and the distribution of luminance values in a scene. The data from this paper has been made available online. PMID- 27271805 TI - [Stress fractures]. AB - Bone stress injuries are due to repetitive mechanical overuse of the skeleton and occur as a result of microscopic lesions sustained when bone is subjected to repeated submaximal stress. Over time accumulation of such injuries can lead to bone failure and fractures. Stress-related bone injuries are relatively common among otherwise healthy persons who have recently started new or intensified forms of physical training activities. Stress injuries lead to typical findings on radiography, bone scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) and need to be discriminated from other conditions, in particular infections and neoplasms. Stress fractures must be differentiated from insufficiency fractures that occur in bones with reduced mechanical resistance or disturbed structure. PMID- 27271807 TI - Perceived depth from shading boundaries. AB - Shading is well known to provide information the visual system uses to recover the three-dimensional shape of objects. We examined conditions under which patterns in shading promote the experience of a change in depth at contour boundaries, rather than a change in reflectance. In Experiment 1, we used image manipulation to illuminate different regions of a smooth surface from different directions. This manipulation imposed local differences in shading direction across edge contours (delta shading). We found that increasing the angle of delta shading, from 0 degrees to 180 degrees , monotonically increased perceived depth across the edge. Experiment 2 found that the perceptual splitting of shading into separate foreground and background surfaces depended on an assumed light source from above prior. Image regions perceived as foreground structures in upright images appeared farther in depth when the same images were inverted. We also found that the experienced break in surface continuity could promote the experience of amodal completion of colored contours that were ambiguous as to their depth order (Experiment 3). These findings suggest that the visual system can identify occlusion relationships based on monocular variations in local shading direction, but interprets this information according to a light source from above prior of midlevel visual processing. PMID- 27271808 TI - Highlight shapes and perception of gloss for real and photographed objects. AB - Gloss perception strongly depends on the three-dimensional shape and the illumination of the object under consideration. In this study we investigated the influence of the spatial structure of the illumination on gloss perception. A diffuse light box in combination with differently shaped masks was used to produce a set of six simple and complex highlight shapes. The geometry of the simple highlight shapes was inspired by conventional artistic practice (e.g., ring flash for photography, window shape for painting and disk or square for cartoons). In the box we placed spherical stimuli that were painted in six degrees of glossiness. This resulted in a stimulus set of six highlight shapes and six gloss levels, a total of 36 stimuli. We performed three experiments of which two took place using digital photographs on a computer monitor and one with the real spheres in the light box. The observers had to perform a comparison task in which they chose which of two stimuli was glossiest and a rating task in which they rated the glossiness. The results show that, perhaps surprisingly, more complex highlight shapes were perceived to produce a less glossy appearance than simple highlight shapes such as a disk or square. These findings were confirmed for both viewing conditions, on a computer display and in a real setting. The results show that variations in the spatial structure of "rather simple" illumination of the "extended source" type highlight influences perceived glossiness. PMID- 27271809 TI - Exploring the individual patterns of spiritual well-being in people newly diagnosed with advanced cancer: a cluster analysis. AB - PURPOSE: Research shows that spiritual well-being correlates positively with quality of life (QOL) for people with cancer, whereas contradictory findings are frequently reported with respect to the differentiated associations between dimensions of spiritual well-being, namely peace, meaning and faith, and QOL. This study aimed to examine individual patterns of spiritual well-being among patients newly diagnosed with advanced cancer. METHODS: Cluster analysis was based on the twelve items of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale at Time 1. A combination of hierarchical and k means (non-hierarchical) clustering methods was employed to jointly determine the number of clusters. Self-rated health, depressive symptoms, peace, meaning and faith, and overall QOL were compared at Time 1 and Time 2. RESULTS: Hierarchical and k-means clustering methods both suggested four clusters. Comparison of the four clusters supported statistically significant and clinically meaningful differences in QOL outcomes among clusters while revealing contrasting relations of faith with QOL. Cluster 1, Cluster 3, and Cluster 4 represented high, medium, and low levels of overall QOL, respectively, with correspondingly high, medium, and low levels of peace, meaning, and faith. Cluster 2 was distinguished from other clusters by its medium levels of overall QOL, peace, and meaning and low level of faith. CONCLUSIONS: This study provides empirical support for individual difference in response to a newly diagnosed cancer and brings into focus conceptual and methodological challenges associated with the measure of spiritual well-being, which may partly contribute to the attenuated relation between faith and QOL. PMID- 27271810 TI - Aggressive Metastatic Inflammatory Myofibroblastic Tumor After Allogeneic Stem Cell Transplant With Fatal Pulmonary Toxicity From Crizotinib. AB - Inflammatory myofibroblastic tumors (IMTs) are rare tumors with an intermediate spectrum of biological behavior. IMTs are uncommon secondary malignancies after hematopoietic stem cell transplant. The presence of anaplastic lymphoma kinase rearrangements in 50% of IMTs has led to therapeutic trials with crizotinib, although limited experience remains with crizotinib use in children. We describe the first reported case of a highly aggressive and metastatic IMT (secondary malignancy) in an 8-year-old girl following umbilical cord blood transplant. Although tumor response was demonstrated with anaplastic lymphoma kinase inhibition, she later developed fatal pulmonary toxicity from diffuse alveolar damage, a feature felt most likely to be due to crizotinib. PMID- 27271811 TI - Liver Transplantation in LCH: Risk Reactivation or Wait Till Decompensation? PMID- 27271812 TI - Predominant Neurologic Manifestations Seen in a Patient With a Biallelic Perforin1 Mutation (PRF1; p.R225W). AB - Neurological manifestations in familial hemophagocytic lymphohistiocytosis (FHL) are common, seen in up to 73% of patients in their course of disease. However, in majority of the cases central nervous system manifestations are associated with other clinical and laboratory parameters of hemophagocytic lymphohistiocytosis. We report here a case with FHL2 in whom hemophagocytic lymphohistiocytosis was a presenting manifestation which responded to specific therapy, however, there was isolated central nervous system relapse while patient was in remission and off therapy. FHL2 was confirmed on the basis of reduced perforin expression and homozygous mutation in PRF1at codon 637 in exon 3 (c.673C>T p.Arg225Trp). PMID- 27271813 TI - Oral Pyogenic Granuloma After Bone Marrow Transplant in the Pediatric/Adolescent Population: Report of 5 Cases. AB - Pyogenic granuloma (PG) is a benign, neoplastic, soft tissue growth of granulation and fibrous tissue that may rarely occur in the mouth of patients after hematopoietic cell transplant (HCT). This case series describes 5 pediatric/adolescent patients who developed oral PG after HCT for acute lymphoblastic leukemia, Fanconi anemia, nodular sclerosis Hodgkin's lymphoma, or junctional epidermolysis bullosa. The underlying mechanism for the appearance of oral PG after HCT is unknown, but it is suggested that calcineurin inhibitors used for graft versus host disease (GVHD) may play a role, as all patients were on cyclosporine A or tacrolimus at the time of development of oral PG. Three of the patients were being treated for chronic GVHD, and 1 other treated for acute GVHD. Overall, this report illustrates that PG should be considered in the differential diagnoses when encountering oral lesions in pediatric/adolescent patients after undergoing HCT, especially in the context of chronic GVHD and calcineurin inhibitors use. PMID- 27271814 TI - Subcortical DNET in a Patient With an Enzymatic Deficiency: A Rare Case and Review of the Literature. AB - PURPOSE: This case report describes a toddler with a medical history of biotinidase deficiency who presented with atypical seizures due to a brain tumor. METHODS: This is a case report. RESULTS: Electroencephalogram revealed a frontal lobe mass, with magnetic resonance imaging confirmation of a mass extending from the frontal lobe into the genu and anterior corpus callosum. She underwent a near total resection, and pathology identified a dysembryoplastic neuroepithelial tumor. The patient is now seizure free and clinically doing well. CONCLUSIONS: Children with biotinidase deficiency and atypical seizures should receive a full electroencephalogram evaluation, as brain tumors continue to be on the differential for seizures in this patient population. PMID- 27271815 TI - Ontogenetic shifts in fishes between vegetated and unvegetated tidepools: assessing the effect of physical structure on fish habitat selection. AB - The aim of this study of tidepool fishes was analyse variation in their use of intertidal habitats (rocky shore, mangrove and salt marsh). Specimens were collected during wet and dry periods from 18 tidepools in the three habitats. A total of 7690 specimens, belonging to 19 families and 30 species, was captured. The fish assemblage in rocky shore pools was clearly distinct from that of vegetated habitats (mangrove and salt marshes). The rocky shore fauna was dominated by permanent resident species, whereas pools in mangrove and salt marsh habitats were inhabited primarily by opportunistic and transient species. Habitat segregation by ontogenetic stage (e.g. smaller individuals in mangroves, intermediate size classes in salt marsh and sub-adults/adults on rocky shores) indicates age-related migration in response to the physical structure of these habitats and to the natural history of each fish species. These findings are important for the development of effective conservation and management plans for intertidal fishes. PMID- 27271816 TI - Effect of amino acid substitution in the hydrophobic face of amphiphilic peptides on membrane curvature and perturbation: N-terminal helix derived from adenovirus internal protein VI as a model. AB - The N-terminal amphipathic helical segment of adenovirus internal protein VI (AdVpVI) plays a critical role in viral infection. Here, we report that the peptide segment corresponding to AdVpVI (positions 33-55) can induce positive membrane curvature together with membrane perturbation. The enhanced perturbation ability of the peptide was observed for membranes containing negatively charged phospholipids. Based on the liposome leakage assay, substitution of leucine at position 40 to other aliphatic (isoleucine) and aromatic (phenylalanine and tryptophan) residues yielded a similar degree of membrane perturbation by the peptides, which was considerably diminished by the substitution to glutamine. Further studies using the wild-type AdVpVI (33-55) (WT) and phenylalanine substituted peptides (L40F) demonstrated that both peptides have positive membrane-curvature-inducing ability. These peptides showed higher binding affinity to 50-nm large unilamellar vesicles (LUVs) than to 200-nm LUVs. However, no enhanced perturbation by these peptides was observed for 50-nm LUVs compared to 200-nm LUVs, suggesting that both the original membrane curvature and the additional strain due to peptide insertion affect the membrane perturbation ability of these peptides. In the case of L40F, this peptide rather had a lower membrane perturbation ability for 50-nm LUVs than for 200-nm LUVs, which can be attributed to possible shallower binding of L40F on membranes. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 430-439, 2016. PMID- 27271817 TI - A Miniaturized Therapeutic Chromophore for Multiple Metal Pollutant Sensing, Pathological Metal Diagnosis and Logical Computing. AB - The efficacy of a miniaturized unimolecular analytic system is illustrated. The easily accessible therapeutic chromophore "temoporfin", which responds differentially to bound metals at multiple wavelengths of Q-band absorption using chemometric analysis, expeditiously detects and discriminates a wide range of metals regarded as priority pollutants in water and hence may also be used for diagnosis of medically relevant metals in human urine. The molecule was further investigated as an electronic logic device, e.g. keypad lock device, to authorize multiple highly secure chemical passwords for information protection. PMID- 27271819 TI - Pencil it in: pencil drawn electrochemical sensing platforms. AB - Inspired by recent reports concerning the utilisation of hand drawn pencil macroelectrodes (PDEs), we report the fabrication, characterisation (physicochemical and electrochemical) and implementation (electrochemical sensing) of various PDEs drawn upon a flexible polyester substrate. Electrochemical characterisation reveals that there are no quantifiable electrochemical responses upon utilising these PDEs with an electroactive analyte that requires an electrochemical oxidation step first, therefore the PDEs have been examined towards the electroactive redox probes hexaammineruthenium(iii) chloride, potassium ferricyanide and ammonium iron(ii) sulfate. For the first time, characterisation of the number of drawn pencil layers and the grade of pencil are examined; these parameters are commonly overlooked when utilising PDEs. It is demonstrated that a PDE drawn ten times with a 6B pencil presented the most advantageous electrochemical platform, in terms of electrochemical reversibility and peak height/analytical signal. In consideration of the aforementioned limitation, analytes requiring an electrochemical reduction as the first process were solely analysed. We demonstrate the beneficial electroanalytical capabilities of these PDEs towards p-benzoquinone and the simultaneous detection of heavy metals, namely lead(ii) and cadmium(ii), all of which are explored for the first time utilising PDEs. Initially, the detection limits of this system were higher than desired for electroanalytical platforms, however upon implementation of the PDEs in a back-to-back configuration (in which two PDEs are placed back-to-back sharing a single connection to the potentiostat), the detection limits for lead(ii) and cadmium(ii) correspond to 10 MUg L(-1) and 98 MUg L(-1) respectively within model aqueous (0.1 M HCl) solutions. PMID- 27271818 TI - The immunology of the vermiform appendix: a review of the literature. AB - This literature review assesses the current knowledge about the immunological aspects of the vermiform appendix in health and disease. An essential part of its immunological function is the interaction with the intestinal bacteria, a trait shown to be preserved during its evolution. The existence of the appendiceal biofilm in particular has proved to have a beneficial effect for the entire gut. In assessing the influence of acute appendicitis and the importance of a normally functioning gut flora, however, multiple immunological aspects point towards the appendix as a priming site for ulcerative colitis. Describing the immunological and microbiotical changes in the appendix during acute and chronic inflammation of the appendix, this review suggests that this association becomes increasingly plausible. Sustained by the distinct composition of cells, molecules and microbiota, as well as by the ever more likely negative correlation between the appendix and ulcerative colitis, the idea of the appendix being a vestigial organ should therefore be discarded. PMID- 27271820 TI - Recovery from hybrid breakdown in a marine invertebrate is faster, stronger and more repeatable under environmental stress. AB - Understanding how environmental stress alters the consequences of hybridization is important, because the rate of hybridization and the likelihood of hybrid speciation both appear elevated in harsh, disturbed or marginal habitats. We assessed fitness, morphometrics and molecular genetic composition over 14 generations of hybridization between two highly divergent populations of the marine copepod Tigriopus californicus. Replicated, experimental hybrid populations in both control and high-salinity conditions showed a decline in fitness, followed by a recovery. Recovery was faster in the salinity stress treatment, returning to parental levels up to two generations earlier than in the control. This recovery was stable in the high-salinity treatment, whereas in the control treatment, fitness dropped back below parental levels at the final time point. Recovery in the high-salinity treatment was also stronger in terms of competitive fitness and heat-shock tolerance. Finally, consequences of hybridization were more repeatable under salinity stress, where among-replicate variance for survivorship and molecular genetic composition was lower than in the control treatment. In a system with low effective population sizes (estimates ranged from 17 to 63), where genetic drift might be expected to be the predominate force, strong selection under harsh environmental conditions apparently promoted faster, stronger and more repeatable recovery from depressed hybrid fitness. PMID- 27271821 TI - Wheat (Triticum aestivum L.)-based intercropping systems for biological pest control. AB - Wheat (Triticum aestivum L.) is one of the most cultivated crops in temperate climates. As its pests are mainly controlled with insecticides that are harmful to the environment and human health, alternative practices such as intercropping have been studied for their potential to promote biological control. Based on the published literature, this study aimed to review the effect of wheat-based intercropping systems on insect pests and their natural enemies. Fifty original research papers were obtained from a systematic search of the peer-reviewed literature. Results from a vote-counting analysis indicated that, in the majority of studies, pest abundance was significantly reduced in intercropping systems compared with pure stands. However, the occurrence of their natural enemies as well as predation and parasitism rates were not significantly increased. The country where the studies took place, the type of intercropping and the crop that was studied in the association had significant effects on these results. These findings show that intercropping is a viable practice to reduce insecticide use in wheat production systems. Nevertheless, other practices could be combined with intercropping to favour natural enemies and enhance pest control. (c) 2016 Society of Chemical Industry. PMID- 27271822 TI - iNuc-STNC: a sequence-based predictor for identification of nucleosome positioning in genomes by extending the concept of SAAC and Chou's PseAAC. AB - The nucleosome is the fundamental unit of eukaryotic chromatin, which participates in regulating different cellular processes. Owing to the huge exploration of new DNA primary sequences, it is indispensable to develop an automated model. However, identification of novel protein sequences using conventional methods is difficult or sometimes impossible because of vague motifs and the intricate structure of DNA. In this regard, an effective and high throughput automated model "iNuc-STNC" has been proposed in order to identify accurately and reliably nucleosome positioning in genomes. In this proposed model, DNA sequences are expressed into three distinct feature extraction strategies containing dinucleotide composition, trinucleotide composition and split trinucleotide composition (STNC). Various statistical models were utilized as learner hypotheses. Jackknife test was employed to evaluate the success rates of the proposed model. The experiential results expressed that SVM, in combination with STNC, has obtained an outstanding performance on all benchmark datasets. The predicted outcomes of the proposed model "iNuc-STNC" is higher than current state of the art methods in the literature so far. It is ascertained that the "iNuc-STNC" model will provide a rudimentary framework for the pharmaceutical industry in the development of drug design. PMID- 27271823 TI - Critical Influence of 5-Hydroxymethylfurfural Aging and Decomposition on the Utility of Biomass Conversion in Organic Synthesis. AB - Spectral studies revealed the presence of a specific arrangement of 5 hydroxymethylfurfural (5-HMF) molecules in solution as a result of a hydrogen bonding network, and this arrangement readily facilitates the aging of 5-HMF. Deterioration of the quality of this platform chemical limits its practical applications, especially in synthesis/pharma areas. The model drug Ranitidine (Zantac(r)) was synthesized with only 15 % yield starting from 5-HMF which was isolated and stored as an oil after a biomass conversion process. In contrast, a much higher yield of 65 % was obtained by using 5-HMF isolated in crystalline state from an optimized biomass conversion process. The molecular mechanisms responsible for 5-HMF decomposition in solution were established by NMR and ESI MS studies. A highly selective synthesis of a 5-HMF derivative from glucose was achieved using a protecting group at O(6) position. PMID- 27271826 TI - [The psychodiagnostic aspects of the compliance with treatment in the course of medical rehabilitation]. AB - The objective of the present study was to elucidate the possibility of using psycho-diagnostic tools for the preventive diagnostics of the patients' adherence to the treatment in the course of medical rehabilitation. The article presents the overview of the available literature concerning the problem of interest. It is shown that the important factors of preventive diagnostics of the compliance include the peculiar steady-state and dynamic features of the individual patients presenting with chronic pathology, their current emotional state, intellectual and motivational preparedness for the active and meaningful participation in the rehabilitation process. The psychometric characteristics of the main methodological techniques that can be used for diagnostics of these parameters are described. Also reported are the data illustrating the necessity of the neuropsychological studies of the higher mental functions as well as formal standard testing and clinical interviewing of the patients by health providers for the purpose of determining the patient's preparedness for the efficient engagement in the process of rehabilitation. PMID- 27271825 TI - Hybrid kappa?lambda antibody is a new serological marker to diagnose autoimmune pancreatitis and differentiate it from pancreatic cancer. AB - The only generally accepted serological marker currently used for the diagnosis of autoimmune pancreatitis (AIP) is IgG4. Our aim was mainly to determine whether hybrid kappa?lambda antibody can help to diagnose AIP and to differentiate it from pancreatic cancer. We established an enzyme-linked immunosorbent assay (ELISA) system to measure the levels of hybrid kappa?lambda antibodies in human sera. Sera were obtained from 338 patients, including 61 with AIP, 74 with pancreatic cancer, 50 with acute pancreatitis, 40 with ordinary chronic pancreatitis, 15 with miscellaneous pancreatic diseases, and 98 with normal pancreas. Our study showed levels of hybrid kappa?lambda antibodies in the AIP group were significantly higher than in the non-AIP group (P < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of AIP were 80.3%, 91%, 66.2% and 95.5% respectively. Furthermore, the combined measurement of serum hybrid kappa?lambda antibody and IgG4 tended to increase the sensitivity although the difference was not statistically significant (90.2% vs. 78.7%, P = 0.08), compared to measurement of IgG4 alone. Our findings suggest that hybrid kappa?lambda antibody could be a new serological marker to diagnose AIP and differentiate it from pancreatic cancer. PMID- 27271827 TI - [The results of rehabilitation of the patients presenting with arterial hypertension: the types of adaptation, the vegetative status, and intracardial hemodynamics]. AB - AIM: The objective the present work was to study the changes of the types of adaptation in the patients presenting with arterial hypertension under the influence of the spa and health resort-based rehabilitative treatment. MATERIAL AND METHODS: The study included 50 patients with essential hypertension at the age from 54.0 to 62.0 (mean 58.0) years given a course of the spa and health resort-based rehabilitative treatment. All the patients underwent electrocardiographic and echocardiographic examination for the assessment of the systolic and diastolic left ventricular functions. Cardiointervalography with the use of the ORTO Expert diagnostic system was performed in the patients at rest and during the active orthostatic test (AOT); the types of the adaptation were evaluated. The patients were divided into 2 groups depending on the results of repeated AOT obtained after rehabilitation. Group 1 was comprised of the patients showing the improvement of adaptation (n=24), group 2 consisted of the patients in whom the level of adaptation remained unaltered (n=26). RESULTS: The structural characteristics of echocardiography estimated in both groups were not significantly different. The number of patients in group 1 showing the satisfactory level of adaptation intensity in the absence of its failures increased significantly. In group 2, a significant decrease of the following AOT parameters was documented: the tension index of the regulatory system (p=0.02), the standard deviation of NN-intervals (SDNN) (p=0.03), and root mean square of successive differences (RMSSD) (p=0.02). The multiple logistic regression analysis showed that the factors associated with the positive effect of rehabilitation were the normal and low degree of regulatory system tension (p=0.01) and the initially adequate or reduced response in the orthostatic test (p=0.04). CONCLUSION: The improvement of rehabilitation of the adaptive capacity was documented in as many as 48% of the patients who had undergone the spa and health resort-based rehabilitative treatment. The absence of positive dynamics or deterioration of adaptation were associated with the increase of the sympathetic activity at rest and in response to the AOT. The beneficial effect of rehabilitation was observed in the patients with the initially normal or low tension of regulatory systems and with the adequate or reduced baseline response in AOT. PMID- 27271828 TI - [The investigation into dynamics of depression level and the quality of life in the patients after myocardial infarction under the influence of the program of physical rehabilitation]. AB - The evaluation of the psychological condition of the patients who survived myocardial infarction and its correction taking into consideration the peculiar features of the individual reaction to the disease are the indispensable components of physical rehabilitation. The present article was designed to report the results of the study on the influence of the authors' physical rehabilitation program on the prevalence of depression and the life quality characteristics of the patients treated after myocardial infarction during the follow-up period. MATERIAL AND METHODS: The patients of the main group (n=30) were enrolled in the original physical rehabilitation program. Those comprising the group of comparison (n=30) were given a course of rehabilitation in accordance with the scheme that had been recommended by the leading scientists and generally accepted in the Ukraine for the patients recovering after myocardial infarction under conditions of the out-patient clinics, spa and health resort facilities or convalescent centers. RESULTS AND DISCUSSION: The study has demonstrated that the patients of both groups exhibited positive dynamics of their clinical condition (e.g. the decrease in the number of depressed subjects); however, this tendency was more pronounced in the main group where the number of the patients experiencing depression decreased by 61% at the end of the observation period (r<0,05). The analysis of the causes of anxiety associated with this pathology in the individual patients has demonstrated that the main factors responsible for the deterioration of the quality of life were the necessity of treatment, the limitations on the everyday physical activity, and the feeling of emotional tension. Moreover, the positive dynamics of the characteristics being evaluated was documented in the patients of the main group which gives reason to conclude that the program of physical rehabilitation proposed by the authors for the treatment of the patients after myocardial infarction is highly efficient during the follow-up period. Suffice it to say that 23 (76,7%) patients of the main group did not consider their lives as of poor quality by the end of the study period (r<0,01). There were only 18 such patients in the control group (r<0,05). CONCLUSION: The results of the present study provide a basis for recommending the proposed authors' program of physical rehabilitation for the patients treated after myocardial infarction with the emphasis on the necessity to do special dynamic exercises for the cervical and thoraco-cervical spine segments to be supplemented by the relevant educational program. PMID- 27271830 TI - [The possibilities for the correction of the co-morbid anxiety and depressive disorders in the patients suffering from chronic obstructive pulmonary disease by the methods of climatic therapy]. AB - The present study included 142 patients presenting with grade I-III chronic obstructive pulmonary disease (COPD) treated based at a spa and health resort (SHR) facility located on the southern coast of the Crimea. The psycho-diagnostic testing was performed with the use of the Hamilton Rating Scale for Depression (HDRS) and the Ch.D. Spielberger - Yu.L. Khanin scale for reactive (situational) and personal anxiety. The anxiety-depressive disorders were diagnosed in 59,2% of the patients; their intensity correlated with the severity of COPD. The questionnaire study based at the Spilberger-Khanin made it possible to document the presence of moderate and severe anxiety in 68,3% of the patients. It was shown that a course of the spa and health resort-based treatment produced beneficial effect on the psycho-functional status of the patients with COPD that was especially well apparent in those with the mild form of COPD. PMID- 27271829 TI - [The state of receptor-dependent signal pathways in the agranulocytes from the peripheral blood of the reconvalescent patients following community-acquired pneumonia under the influence of microwave radiation]. AB - The present article reports the study of the influence of low-intensity microwave radiation on the state of the JAK/STAT-signaling pathways in the mononuclear cells and the intercellular levels of the molecules maintaining the functioning of this pathway. The experiments on the model of intercellular interactions in the whole blood cell culture obtained during the convalescence phase of community acquired bacterial pneumonia were designed to elucidate the effects of the cell cell interactions in the culture exposed to electromagnetic radiation with a frequency of 1000 MHz and power flux density 0.1 mcW/cm2 on the intracellular levels of total and phosphorylated species of JAK-kinases, STAT-factors and SOCS proteins. It is concluded that sensitivity of intracellular signaling systems to the effects of low-intensity microwave radiation manifests itself in the form of increased intracellular concentrations of Janus kinases and SOCS proteins with a simultaneous decrease in the level of STAT factors. PMID- 27271831 TI - [Correction of the functional state of the autonomous nervous system in the women presenting with the postmastectomy syndrome at the stationary stage of the rehabilitative treatment]. AB - A frequent consequence of the treatment of breast cancer is the postmastectomy syndrome that combines psycho-emotional and functional disorders in various body systems. AIM: The objective of the present study was to evaluate the influence of the program of differential physical rehabilitation on the functional state of the autonomic nervous system in the women with the postmastectomy syndrome at the stationary stage of the rehabilitative treatment. MATERIAL AND METHODS: The study included 50 presenting with the postmastectomy syndrome following radical mastectomy as described by J.L. Madden. The patients were randomly divided into two groups comprised of 25 patients each. The main group consisted of the women at the mean age of 55,44+/-1,06 years, the group of comparison (2) was composed of the women at the mean age of 55,60+/-1,14 years. The program of the rehabilitative treatment of the patients in group 1 envisaged the use of the physical therapeutic modalities chosen on an individual basis in agreement with the basic principles of medical gymnastics including the differential selection of static and dynamic respiratory maneuvers with due regard for the type of vegetative regulation in a given patient, post-isometric relaxation, Vodder's manual lymphatic drainage and autotraining as described by J.H. Suhultz. The patients comprising the group of comparison performed therapeutic physical exercises as described by T.I. Grushina. The analysis of the literature and empirical data was combined with that of the heart rate variability was measured twice: within days 2-3 after the surgical intervention and on days 19-20 of the hospital stay. The methods of mathematical statistics were employed to treat the data obtained. RESULTS: The study has demonstrated reduced reserves of vegetative support, the overall decrease of the heart rate variability, and enhanced tension of the adaptive mechanisms in this group of women. Moreover, it showed the positive outcome of the physical rehabilitation program designed to correct most of the time-related and spectral parameters of the heart rate variability and gave evidence of the significant improvement of the total activity of the regulatory systems due to the enhancement of the high-frequency, low-frequency and very low-frequency components of the spectrum. The values of the stress index and the mode amplitude were reduced whereas the adaptive capabilities of the autonomic nervous system in women of the main group were extended. CONCLUSION: The proposed program of differential physical rehabilitation can be employed in the practical work of the specialized healthcare facilities for the correction of the functional state of the autonomic nervous system in the women with the postmastectomy syndrome. PMID- 27271832 TI - [The isokinetic evaluation of the knee joint function following the autoplastic correction of its anterior cross-shaped ligament]. AB - The flexors/extensors imbalance can be a cause knee instability and therefore lead to progression of osteoarthritis. The isokinetic evaluation of the strength of flexors after the autoplastic reconstruction the anterior cross-shaped (cruciate) ligament (ACL) is of primary importance bearing in mind that certain authors have reported a persistent deficiency in flexor strength after surgery. AIM: The purpose of the present study was to objectively evaluate the isokinetic function of the knee during each treatment stage and estimate the influence of harvesting semitendinosus/gracilis tendon (SGT) on the knee flexion. MATERIAL AND METHODS: During the period from 2012 to 2014, a total of 44 patients (20 women and 24 men) presenting with ACL rupture were available for the examination. All the patients underwent the isokinetic evaluation of the knee function before operation, 6-8 weeks and 3-4 months after the arthroscopic ACL reconstruction with the use of the SGT graft. The patients were divided into two groups. The first group was comprised of 22 subjects who were treated in accordance with the standard protocol of therapeutic physical exercises starting from week 6 after the initiation of the physiotherapeutic rehabilitative measures. The second group consisted of 22 patients who had to perform the isokinetic training within 6-8 weeks after surgery. RESULTS: The results of the study indicate that all the patients suffering injuries to the anterior cross-shaped ligaments had well apparent flexor/extensor imbalance. In those of the first group, the flexor imbalance amounted to 25-35% while the extensor imbalance was 10-15% within 3-4 months after the surgery. The second group showed a 10-15% flexor imbalance and 2 5% extensor imbalance after 3-4 months. CONCLUSION: The isokinetic testing provides a tool for the objective evaluation of the knee function. It helps to reveal the high effectiveness of isokinetic rehabilitation protocol leading to the recovery of the patients within 3-4 months after the surgery. It can be assumed based on the results of the present study that harvesting of the semitendinosus/gracilis tendon does not exert any negative influence on the knee flexion strength given the rehabilitation program includes the isotonic training protocol. PMID- 27271833 TI - [The clinical effectiveness of the application of interferential currents for the combined treatment of onychopathies associated with psoriasis and eczema]. AB - The frequency of the development of clinically significant changes in the nail plates was estimated in the present study that included 454 patients presenting with psoriasis and 140 patients with eczema characterized by the localization of the pathological process on the skin of the wrists and/or feet. The changes in the nail plates were shown to occur in 56,2% of the patients with psoriasis and in 90,7% of those suffering from eczema. The capillaroscopy of the microvessels feeding the affected nails was carried out to determine the type of the capillaroscopic picture. The patients with onychopathies were largely characterized by the spastic-atonic type of the changes in the microcirculatory bed. The changes of this type were documented in 86,5% of the patients with psoriatic onychopathy and in 83,9% of those presenting with onychodystrophy associated with eczema. The effectiveness of the combined treatment including the application of interferential currents was estimated in comparison with that of standard therapy. It was shown that the use of interferential currents for the treatment of the patients with psoriasis results in a decrease of the severity index of nail damage by 47,8% in comparison with 18,1% in the case of standard medicamentous therapy. Similarly, a 77,2 and 51,3% decrease of the index of severity was documented in the patients with eczema after their treatment with the use of interferential currents and standard medicamentous therapy, respectively. PMID- 27271834 TI - [The influence of low-frequency pulsed electric and magnetic signals or their combination on the normal and modified fibroblasts (an experimental study)]. AB - The results of clinical studies give evidence of the beneficial preventive and therapeutic effects of the "Tiline-EM" physiotherapeutic device designed for the combined specific treatment of the skin regions onto which both discomfort and pain sensations are directly projected, reflectively active sites and zones, as well as trigger zones with the use of low-frequency pulsed electric current and magnetic field. The efficient application of the device requires the understanding of the general mechanisms underlying such action on the living systems including those operating at the cellular and subcellular levels. The objective of the present study was the investigation of the specific and complex effects produced by the low-frequency pulses of electric current and magnetic field generated in the physiotherapeutic device "Tiline-EM" on the viability, proliferative activity, and morphofunctional characteristics of normal skin fibroblasts and the transformed fibroblast line K-22. It has been demonstrated that the biological effects of the electric and magnetic signals vary depending on the type of the cell culture and the mode of impact. The transformed fibroblasts proved to be more sensitive to the specific and complex effects of electric and magnetic pulses than the normal skin fibroblasts. The combined action of the electric and magnetic signals was shown to have the greatest influence on both varieties of fibroblasts. It manifests itself in the form of enhanced viability, elevated proliferative and synthetic activity in the cultures of transformed fibroblasts and as the acceleration of cell differentiation in the cultures of normal fibroblasts. The effect of stimulation of dermal fibroblast differentiation in response to the combined treatment by the electric and magnetic signals is of interest from the standpoint of the physiotherapeutic use of the "Tiline-EM" device for the purpose of obtaining fibroblasts cultures to be employed in regenerative therapy and the treatment of skin injuries in cosmetology, aesthetic and regenerative medicine. PMID- 27271835 TI - [Modern approaches to the use of neurotropic physical therapy in arterial hypertension]. AB - The development and introduction into clinical practice of non-pharmacological methods for the prevention and treatment of arterial hypertension is a primary objective of modern physical therapy, especially as regards the neurotropic influences. This article was designed to report the results of the investigation into the hypotensive effect of transcerebral magnetic therapy obtained during the treatment of 60 patients presenting with arterial hypertension. The study included the comparative examination of two randomly formed groups containing 30 patients each. The patients of the main group received transcerebral magnetic therapy (to the frontal region) while those in the group of comparison were given magnetotherapy at the collar region. The study has demonstrated that transcerebral magnetic therapy given to the patients of the main group was a more efficient treatment than magnetotherapy at the collar region since it produced a more pronounced hypotensive effect irrespective of the initial hemodynamic type. PMID- 27271836 TI - [The application of climatic therapy in the health resorts of the Black Sea coast of the Caucasus: the current state-of-the-art and the prospects for the further development]. AB - The present review summarizes the data published in the domestic and foreign literature concerning the history of climatic therapy, the current concepts of the mechanisms of action of the climatic and weather factors on the human body, the modern therapeutic modalities and technologies for health promotion. We consider not only the achievements but also the problems arising from insufficient knowledge of the impacts of current climate and extreme weather conditions on the state of human health and some disputable issues of the new methods and technologies of climatic therapy. IN CONCLUSION: the promising areas of further research and developments pertaining to climatic therapy as practiced under conditions of the Black Sea coast resorts. PMID- 27271837 TI - [The spa-health resort and touristic-recreational facilities of the region: the methodological aspects of their development]. AB - The correction and optimization of the motor activity of the patients are currently the main priorities of all rehabilitative and recreational activities based at the spa and health resort facilities. The forms of such activities include walking tours and excursion trips. In other words, the excursion potential is one of the very important attributes of the recreational recourses. Under the current conditions characterized by the rapid socio-economic changes, the studies concerning the structural and functional transformation of spa and health resorts, recreational and tourist facilities acquire special importance, both from the humanitarian and economic points of view. The results of these studies may greatly contribute to the organization and the further development of rehabilitative and recreational activities based at the spa and health resort facilities, recreational and tourist centers taking into consideration their evolution. MATERIAL AND METHODS: The objective of the present article is to analyze the structure and functions of the recreation and tourist centres as well as the modes of their cooperation with the spa and health resort facilities. In other words, these structures and their functions are both the object and the subject of the present study. The methodology of the study is based on the logical analysis of the development of the recreational and tourist systems in the framework of the evolutionary approach. RESULTS: (1) the notions of "tourist destination" and "recreation" have been substantiated; (2) the results of the studies carried out at the Institute of Physical Culture, Sports and Tourism and the Petrozavodsk State University have been used to elaborate the affiliate international Master Degree program "Project management in the tourism industry". The main emphasis in this program is placed on the necessity and methods of the improvement of recreational activities and more efficacious utilization of the climatic factors and the health resort infrastructure as well as personnel training for the sake of improvement of services to the visitors. CONCLUSION: The analysis of various aspects of recreation and tourism development has demonstrated that the services provided by the recreational and tourist systems in cooperation with the health resort infrastructure open up new employment opportunities and thus reduce the risk of social tension. The prospects for the continuation of investigations along these lines are associated with the extension of the recreational and touristic activities over the rural and countryside localities with special reference to the trans-border interactions as well as specific features of the tourist and recreational resources of the given regions and territories. PMID- 27271838 TI - Effects of dietary supplementation of bacteriophages against enterotoxigenic Escherichia coli (ETEC) K88 on clinical symptoms of post-weaning pigs challenged with the ETEC pathogen. AB - The present study was performed to investigate the effects of dietary supplementation of bacteriophages (phages) against enterotoxigenic Escherichia coli (ETEC) K88 as a therapy against the ETEC infection in post-weaning pigs. Two groups of post-weaning pigs aged 35 days, eight animals per group, were challenged with 3.0 * 1010 colony forming units of ETEC K88, a third group given the vehicle. The unchallenged group and one challenged group were fed a basal nursery diet for 14 days while the remaining challenged group was fed the basal diet supplemented with 1.0 * 107 plaque forming units of the phage per kg. Average daily gain (ADG), goblet cell density and villous height:crypt depth (VH:CD) ratio in the intestine were less in the challenged group than in the unchallenged group within the animals fed the basal diet (p < 0.05); the reverse was true for rectal temperature, faecal consistency score (FCS), E. coli adhesion score (EAS) in the intestine, serum interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations and digesta pH in the stomach, caecum and colon. The ETEC infection symptom within the challenged animals was alleviated by the dietary phage supplementation (p < 0.05) in ADG, FCS, EAS in the jejunum, serum TNF-alpha concentration, digesta pH in the colon, goblet cell density in the ileum and colon and VH:CD ratio in the ileum. Moreover, the infection symptom tended to be alleviated (p < 0.10) by the phage supplementation in rectal temperature, EAS in the ileum and caecum, and VH:CD ratio in the duodenum and jejunum. However, EAS in the colon, digesta pH in the stomach and caecum, and goblet cell density in the jejunum did not change due to the dietary phage. Overall, results indicate that the phage therapy is effective for alleviation of acute ETEC K88 infection in post-weaning pigs. PMID- 27271840 TI - Virtual Planning, Control, and Machining for a Modular-Based Automated Factory Operation in an Augmented Reality Environment. AB - This study presents a modular-based implementation of augmented reality to provide an immersive experience in learning or teaching the planning phase, control system, and machining parameters of a fully automated work cell. The architecture of the system consists of three code modules that can operate independently or combined to create a complete system that is able to guide engineers from the layout planning phase to the prototyping of the final product. The layout planning module determines the best possible arrangement in a layout for the placement of various machines, in this case a conveyor belt for transportation, a robot arm for pick-and-place operations, and a computer numerical control milling machine to generate the final prototype. The robotic arm module simulates the pick-and-place operation offline from the conveyor belt to a computer numerical control (CNC) machine utilising collision detection and inverse kinematics. Finally, the CNC module performs virtual machining based on the Uniform Space Decomposition method and axis aligned bounding box collision detection. The conducted case study revealed that given the situation, a semi circle shaped arrangement is desirable, whereas the pick-and-place system and the final generated G-code produced the highest deviation of 3.83 mm and 5.8 mm respectively. PMID- 27271839 TI - The Prevalence of Tuberous/Constricted Breast Deformity in Population and in Breast Augmentation and Reduction Mammaplasty Patients. AB - BACKGROUND: The exact prevalence of tuberous breast deformity (TBD) has not been properly investigated and still remains undetermined. We report our data about TBD prevalence with the aim of demonstrating its high prevalence. MATERIALS AND METHODS: A retrospective analysis was performed on preoperative photographs of 1600 Caucasian female patients admitted to our department from January 2009 to July 2014 for augmentation or reduction mammaplasty and other breast clinical conditions. The main features of TBD included a contracted skin envelope, a reduction in breast parenchyma of the lower medial and lateral quadrants, a constricted breast base, abnormal elevation of the inframammary fold, herniation of the breast into the areola with a constricted breast base, and nipple areola complex herniation with a normal breast base. Patients were classified into three groups: breast augmentation group (AUG group), breast reduction group (RED group), and general population group (POP group). RESULTS: Four hundred patients were analyzed for each group (AUG and RED group); 194 patients (48.5 %) and 189 cases (47.3 %), respectively, demonstrated at least one tuberous breast deformity; in 800 patients of the POP group, we found 221 patients (27.6 %) with at least one tuberous breast deformity. CONCLUSIONS: Retrospective analysis reveals a high prevalence of TBD in the general population and in particular in women seeking breast augmentation or breast reduction (about 50 %). TBD is characterized by a wide range of clinical features with a spectrum of degrees. Preoperative evaluation is crucial to achieve an optimum outcome and patient satisfaction. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . PMID- 27271842 TI - Management of a Damaged Implant for Retention of an Overdenture Prosthesis and Fixed Single Crown: Clinical Reports. AB - This article demonstrates a method to salvage an implant that has been damaged or is no longer usable because of a fractured screw that cannot be removed. In the first situation the patient had a Locator abutment that fractured during torqueing of the abutment. Despite the attempt to remove the fractured screw, it was not retrievable, and the internal threads of the implant were damaged in the attempt to remove the screw. Rather than removing the implant or covering it and sleeping the implant, a custom cast post was used to restore the implant to function. A second example describes a patient with a fixed implant crown. The implant was damaged during attempts to remove the fractured screw. A custom post was fabricated and cemented, and a new crown was fabricated. PMID- 27271841 TI - Predicting optimal transmission investment in malaria parasites. AB - In vertebrate hosts, malaria parasites face a tradeoff between replicating and the production of transmission stages that can be passed onto mosquitoes. This tradeoff is analogous to growth-reproduction tradeoffs in multicellular organisms. We use a mathematical model tailored to the life cycle and dynamics of malaria parasites to identify allocation strategies that maximize cumulative transmission potential to mosquitoes. We show that plastic strategies can substantially outperform fixed allocation because parasites can achieve greater fitness by investing in proliferation early and delaying the production of transmission stages. Parasites should further benefit from restraining transmission investment later in infection, because such a strategy can help maintain parasite numbers in the face of resource depletion. Early allocation decisions are predicted to have the greatest impact on parasite fitness. If the immune response saturates as parasite numbers increase, parasites should benefit from even longer delays prior to transmission investment. The presence of a competing strain selects for consistently lower levels of transmission investment and dramatically increased exploitation of the red blood cell resource. While we provide a detailed analysis of tradeoffs pertaining to malaria life history, our approach for identifying optimal plastic allocation strategies may be broadly applicable. PMID- 27271843 TI - Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review. AB - Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with considerable heterogeneity reflected in the 2008 World Health Organization classification. In recent years, genome-wide assessment of genetic and epigenetic alterations has shed light upon distinct molecular subsets linked to dysregulation of specific genes or pathways. Besides fostering our knowledge regarding the molecular complexity of DLBCL types, these studies have unraveled previously unappreciated genetic lesions, which may be exploited for prognostic and therapeutic purposes. Following the last World Health Organization classification, we have witnessed the emergence of new variants of specific DLBCL entities, such as CD30 DLBCL, human immunodeficiency virus-related and age-related variants of plasmablastic lymphoma, and EBV DLBCL arising in young patients. In this review, we will present an update on the clinical, pathologic, and molecular features of DLBCL incorporating recently gained information with respect to their pathobiology and prognosis. We will emphasize the distinctive features of newly described or emerging variants and highlight advances in our understanding of entities presenting a diagnostic challenge, such as T-cell/histiocyte-rich large B-cell lmphoma and unclassifiable large B-cell lymphomas. Furthermore, we will discuss recent advances in the genomic characterization of DLBCL, as they may relate to prognostication and tailored therapeutic intervention. The information presented in this review derives from English language publications appearing in PubMed throughout December 2015. For a complete outline of this paper, please visit: http://links.lww.com/PAP/A12. PMID- 27271844 TI - New Generation Blood Glucose Monitoring System Exceeds International Accuracy Standards. PMID- 27271845 TI - Boluses in Insulin Therapy. AB - Giving a bolus is one major part in multiple dose insulin therapy (MDI) along with basal insulin substitution. To adjust the bolus optimally, different factors like carbohydrate content and composition of the meal, correction factors, and timing have to be considered. Advances in technologies like bolus advisors can assist the patients but still there a several open questions and technical challenges regarding boluses. This commentary provides an opportunity to address several of the above-mentioned factors influencing the result of bolusing. It shall draw attention to those factors and address the current opportunities, for example, continuous subcutaneous insulin infusion (CSII), as well as the need for further studies which can help to improve diabetes insulin therapy by means of the correct use of boluses. PMID- 27271846 TI - Systematic characterization of basophil anergy. AB - BACKGROUND: Cohort studies indicated that in certain individuals the basophils do not respond toward allergens due to a desensitization of their Fc epsilon receptor pathway. Cause and functional role as well as the implications on allergic reactions, however, are not clear yet. METHODS: A cross-sectional study was carried out in the tropical urban environment of Singapore, where the allergic response is dominated by a single allergen (house dust mite; HDM). Blood samples were collected from 476 individuals and analyzed comprehensively to correlate the functional state of their basophils with the clinical state as well as the composition of the cellular and soluble plasma components. RESULTS: Inactivation of basophils ('basophil anergy') was observed in about 10% of the cohort. It was associated with a downregulation of basophil Syk and an apparent reduction in the incidence of allergic rhinitis. Correlations on the cohort level suggest that it represents a transitional state to be passed through during the interconversion of responder and nonresponder state. CONCLUSIONS: Basophil anergy thus seems to function as activation barrier to prevent unwanted reactions against minor allergens. It may therefore be relevant for diagnostic purposes or therapeutic interventions of allergic diseases. PMID- 27271847 TI - Functional diversity of family 3 beta-glucosidases from thermophilic cellulolytic fungus Humicola insolens Y1. AB - The fungus Humicola insolens is one of the most powerful decomposers of crystalline cellulose. However, studies on the beta-glucosidases from this fungus remain insufficient, especially on glycosyl hydrolase family 3 enzymes. In the present study, we analyzed the functional diversity of three distant family 3 beta-glucosidases from Humicola insolens strain Y1, which belonged to different evolutionary clades, by heterogeneous expression in Pichia pastoris strain GS115. The recombinant enzymes shared similar enzymatic properties including thermophilic and neutral optima (50-60 degrees C and pH 5.5-6.0) and high glucose tolerance, but differed in substrate specificities and kinetics. HiBgl3B was solely active towards aryl beta-glucosides while HiBgl3A and HiBgl3C showed broad substrate specificities including both disaccharides and aryl beta glucosides. Of the three enzymes, HiBgl3C exhibited the highest specific activity (158.8 U/mg on pNPG and 56.4 U/mg on cellobiose) and catalytic efficiency and had the capacity to promote cellulose degradation. Substitutions of three key residues Ile48, Ile278 and Thr484 of HiBgl3B to the corresponding residues of HiBgl3A conferred the enzyme activity towards sophorose, and vice versa. This study reveals the functional diversity of GH3 beta-glucosidases as well as the key residues in recognizing +1 subsite of different substrates. PMID- 27271848 TI - Understanding burden in caregivers of colorectal cancer survivors: what role do patient and caregiver factors play? AB - This study investigated how both caregiver and patient factors predict different aspects of burden in colorectal cancer caregivers. One hundred and fifty-three caregiver-survivor dyads separately provided information on patient disease and treatment-related factors, and perceived global health status (EORTC QLQ30), along with caregiver socio-demographic factors, health and care-related activities. Four multiple regression analyses were conducted to assess the influence of caregiver characteristics, patient characteristics and care-related activities on four dimensions of burden from the Caregiver Reaction Assessment scale. Caregiver characteristics significantly predicted health and financial burden (11%-13% of explained variance) with comorbidity and younger age increasing this risk. Patient health, in particular global health status and the presence of a stoma, predicted all burden scores, explaining 14%-22% of variance. Care-related activities was also a significant predictor of all burden scores, explaining an additional 5%-11% of variance, with time involved in caring the most consistent predictor. Results highlight that a combination of factors influence caregiver burden. These results may be used to identify those most at risk, allowing practitioners to deliver tailored effective support. In particular, efforts to alleviate the burden of caring on caregiver schedule may be merited, given that this was the domain in which the burden was greatest. PMID- 27271849 TI - Synthesis, electrochemical properties, and crystal packing of perfluororubrene. AB - A synthesis of perfluorinated rubrene is reported. Electrochemical analysis revealed the significantly increased electron affinity of perfluororubrene compared with non-modified rubrene. Crystallographic investigation revealed two polymorphs and a solvate, each displaying twisted backbone conformations of perfluororubrene. Taken together, these results suggest perfluororubrene will find applications as a new n-type semiconductor. PMID- 27271850 TI - Head and Tibial Acceleration as a Function of Stride Frequency and Visual Feedback during Running. AB - Individuals regulate the transmission of shock to the head during running at different stride frequencies although the consequences of this on head-gaze stability remain unclear. The purpose of this study was to examine if providing individuals with visual feedback of their head-gaze orientation impacts tibial and head accelerations, shock attenuation and head-gaze motion during preferred speed running at different stride frequencies. Fifteen strides from twelve recreational runners running on a treadmill at their preferred speed were collected during five stride frequencies (preferred, +/-10% and +/-20% of preferred) in two visual task conditions (with and without real-time visual feedback of head-gaze orientation). The main outcome measures were tibial and head peak accelerations assessed in the time and frequency domains, shock attenuation from tibia to head, and the magnitude and velocity of head-gaze motion. Decreasing stride frequency resulted in greater vertical accelerations of the tibia (p<0.01) during early stance and at the head (p<0.01) during early and late stance; however, for the impact portion the increase in head acceleration was only observed for the slowest stride frequency condition. Visual feedback resulted in reduced head acceleration magnitude (p<0.01) and integrated power spectral density in the frequency domain (p<0.01) in late stance, as well as overall of head-gaze motion (p<0.01). When running at preferred speed individuals were able to stabilize head acceleration within a wide range of stride frequencies; only at a stride frequency 20% below preferred did head acceleration increase. Furthermore, impact accelerations of the head and tibia appear to be solely a function of stride frequency as no differences were observed between feedback conditions. Increased visual task demands through head gaze feedback resulted in reductions in head accelerations in the active portion of stance and increased head-gaze stability. PMID- 27271852 TI - Anomalous electronic structure and magnetoresistance in TaAs2. AB - The change in resistance of a material in a magnetic field reflects its electronic state. In metals with weakly- or non-interacting electrons, the resistance typically increases upon the application of a magnetic field. In contrast, negative magnetoresistance may appear under some circumstances, e.g., in metals with anisotropic Fermi surfaces or with spin-disorder scattering and semimetals with Dirac or Weyl electronic structures. Here we show that the non magnetic semimetal TaAs2 possesses a very large negative magnetoresistance, with an unknown scattering mechanism. Density functional calculations find that TaAs2 is a new topological semimetal [Z2 invariant (0;111)] without Dirac dispersion, demonstrating that a negative magnetoresistance in non-magnetic semimetals cannot be attributed uniquely to the Adler-Bell-Jackiw chiral anomaly of bulk Dirac/Weyl fermions. PMID- 27271853 TI - Human CIK Cells Loaded with Au Nanorods as a Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immunotherapy and Photothermal Therapy. AB - How to realize targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer has become a great challenge. Herein, we reported for the first time that human cytokine-induced killer cells (CIK) loaded with gold nanorods were used for targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer. Silica-modified gold nanorods were prepared; then incubated with human cytokine-induced killer cells (CIK), resultant human CIK cells loaded with Au nanorods were evaluated for their cytotoxicity, targeted ability of gastric cancer in vitro and in vivo, immunotherapy, and photothermal therapy efficacy. In vitro cell experiment shows that human CIK cells labeled with gold nanorods actively target gastric cancer MGC803 cells, inhibit growth of MGC803 cells by inducing cell apoptosis, and kill MGC803 cells under low power density near-infrared (NIR) laser treatment (808-nm continuous wave laser, 1.5 W/cm(2), 3 min). In vivo experiment results showed that human CIK cells labeled with gold nanorods could target actively and image subcutaneous gastric cancer vessels via photoacoustic imaging at 4 h post injection, could enhance immunotherapy efficacy by up-regulating cytokines such as IL-1, IL-12, IL-2, IL-4, IL-17, and IFN-gamma, and kill gastric cancer tissues by photothermal therapy via direct injection into tumor site under near-infrared (NIR) laser irradiation. High-performance human CIK cells labeled with Au nanorods are a good novel theranostic platform to exhibit great potential in applications such as tumor-targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy in the near future. PMID- 27271854 TI - The kinetic model for slow photoinduced electron transport in the reaction centers of purple bacteria. AB - The present work is related to the investigation of slow kinetics of electron transport in the reaction centers (RCs) of Rhodobacter sphaeroides. Experimental data on the absorption kinetics of aqueous solutions of reaction centers at different modes of photoexcitation are given. It is shown that the kinetics of oxidation and reduction of RCs are well described by the sum of three exponential functions. This allows to suggest a two-level kinetic model for electron transport in the RC as a system of four electron-conformational states which correspond to three balance differential equations combined with state equation. The solution of inverse problem made it possible to obtain the rate constant values in kinetic equations for different times and intensities of exciting light. Analysis of rate constant values in different modes of RC excitation allowed to suggest that two mechanisms of structural changes are involved in RC photo-oxidation. One mechanism leads to the increment of the rate of electron return, another one-to its drop. Structural changes were found out to occur in the RCs under incident light. After light was turned off, the reduction of RCs was determined by the second mechanism. PMID- 27271855 TI - Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism. AB - Recent studies support the idea that abnormalities of the reward system contribute to onset and maintenance of anorexia nervosa (AN). Next to cues coding for overweight, other research suggest cues triggering the proposed starvation dependence to be pivotally involved in the AN pathogenesis. We assessed the characteristics of the cognitive, emotional and physiologic response toward disease-specific pictures of female body shapes, in adult AN patients compared with healthy control (HC) women. Frequency and amplitude of skin conductance response (SCR) in 71 patients with AN and 20 HC were registered during processing of stimuli of three weight categories (over-, under- and normal weight). We then assessed the role of the Val66Met BDNF polymorphism as a potential intermediate factor. AN patients reported more positive feelings during processing of underweight stimuli and more negative feelings for normal- and overweight stimuli. The SCR showed a group effect (P=0.007), AN patients showing overall higher frequency of the response. SCR within patients was more frequent during processing of underweight stimuli compared with normal- and overweight stimuli. The Met allele of the BDNF gene was not more frequent in patients compared with controls, but was associated to an increased frequency of SCR (P=0.008) in response to cues for starvation. A higher positive value of starvation, rather than more negative one of overweight, might more accurately define females with AN. The Met allele of the BDNF gene could partly mediate the higher reward value of starvation observed in AN. PMID- 27271856 TI - Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1. AB - Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6-43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 * 10( 5)). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes. PMID- 27271858 TI - Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex. AB - Electroconvulsive therapy (ECT) is a highly effective and rapidly acting treatment for severe depression. To understand the biological bases of therapeutic response, we examined variations in cortical thickness from magnetic resonance imaging (MRI) data in 29 patients scanned at three time points during an ECT treatment index series and in 29 controls at two time points. Changes in thickness across time and with symptom improvement were evaluated at high spatial resolution across the cortex and within discrete cortical regions of interest. Patients showed increased thickness over the course of ECT in the bilateral anterior cingulate cortex (ACC), inferior and superior temporal, parahippocampal, entorhinal and fusiform cortex and in distributed prefrontal areas. No changes across time occurred in controls. In temporal and fusiform regions showing significant ECT effects, thickness differed between patients and controls at baseline and change in thickness related to therapeutic response in patients. In the ACC, these relationships occurred in treatment responders only, and thickness measured soon after treatment initiation predicted the overall ECT response. ECT leads to widespread neuroplasticity in neocortical, limbic and paralimbic regions and changes relate to the extent of antidepressant response. Variations in ACC thickness, which discriminate treatment responders and predict response early in the course of ECT, may represent a biomarker of overall clinical outcome. Because post-mortem studies show focal reductions in glial density and neuronal size in patients with severe depression, ECT-related increases in thickness may be attributable to neuroplastic processes affecting the size and/or density of neurons and glia and their connections. PMID- 27271857 TI - CACNA1C hypermethylation is associated with bipolar disorder. AB - The CACNA1C gene, encoding a subunit of the L-type voltage-gated calcium channel is one of the best-supported susceptibility genes for bipolar disorder (BD). Genome-wide association studies have identified a cluster of non-coding single nucleotide polymorphisms (SNPs) in intron 3 to be highly associated with BD and schizophrenia. The mechanism by which these SNPs confer risk of BD appears to be through an altered regulation of CACNA1C expression. The role of CACNA1C DNA methylation in BD has not yet been addressed. The aim of this study was to investigate if CACNA1C DNA methylation is altered in BD. First, the methylation status of five CpG islands (CGIs) across CACNA1C in blood from BD subjects (n=40) and healthy controls (n=38) was determined. Four islands were almost completely methylated or completely unmethylated, while one island (CGI 3) in intron 3 displayed intermediate methylation levels. In the main analysis, the methylation status of CGI 3 was analyzed in a larger sample of BD subjects (n=582) and control individuals (n=319). Out of six CpG sites that were investigated, five sites showed significant hypermethylation in cases (lowest P=1.16 * 10(-7) for CpG35). Nearby SNPs were found to influence the methylation level, and we identified rs2238056 in intron 3 as the strongest methylation quantitative trait locus (P=2.6 * 10(-7)) for CpG35. In addition, we found an increased methylation in females, and no difference between bipolar I and II. In conclusion, we find that CACNA1C methylation is associated with BD and suggest that the regulatory effect of the non-coding risk variants involves a shift in DNA methylation. PMID- 27271859 TI - Anxiety-potentiated amygdala-medial frontal coupling and attentional control. AB - Anxiety disorders can be treated both pharmacologically and psychologically, but many individuals either fail to respond to treatment or relapse. Improving outcomes is difficult, in part because we have incomplete understanding of the neurobiological mechanisms underlying current treatments. In a sequence of studies, we have identified 'affective bias-related' amygdala-medial cortical coupling as a candidate substrate underlying adaptive anxiety (that is, anxiety elicited by threat of shock in healthy individuals) and shown that it is also chronically engaged in maladaptive anxiety disorders. We have provided evidence that this circuit can be modulated pharmacologically, but whether this mechanism can be shifted by simple psychological instruction is unknown. In this functional magnetic resonance imaging study, we extend a previously used translational anxiety induction (threat of shock) in healthy subjects (N=43) and cognitive task to include an element of instructed attentional control. Replicating our previous findings, we show that induced anxiety engages 'affective bias-related' amygdala dorsal medial frontal coupling during the processing of emotional faces. By contrast, instructing subjects to attend to neutral shapes (and ignore faces) disengages this circuitry and increases putative 'attentional control-related' coupling between the amygdala and a more rostral prefrontal region. These neural coupling changes are accompanied by corresponding modulation of behavioural performance. Taken together, these findings serve to further highlight the potential role of amygdala-medial frontal coupling in the pathogenesis of anxiety and highlight a mechanism by which it can be modulated via psychological instructions. This, in turn, generates hypotheses for future work exploring the mechanisms underlying psychological therapeutic interventions for anxiety. PMID- 27271860 TI - A mega-analysis of fixed-dose trials reveals dose-dependency and a rapid onset of action for the antidepressant effect of three selective serotonin reuptake inhibitors. AB - The possible dose-dependency for the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) remains controversial. We believe we have conducted the first comprehensive patient-level mega-analysis exploring this issue, one incentive being to address the possibility that inclusion of low-dose arms in previous meta-analyses may have caused an underestimation of the efficacy of these drugs. All company-sponsored, acute-phase, placebo-controlled, fixed-dose trials using the Hamilton Depression Rating Scale (HDRS) and conducted to evaluate the effect of citalopram, paroxetine or sertraline in adult major depression were included (11 trials, n=2859 patients). The single-item depressed mood, which has proven a more sensitive measure to detect an antidepressant signal than the sum score of all HDRS items, was designated the primary effect parameter. Doses below or at the lower end of the usually recommended dose range (citalopram: 10-20 mg, paroxetine: 10 mg; sertraline: 50 mg) were superior to placebo but inferior to higher doses, hence confirming a dose-dependency to be at hand. In contrast, among doses above these, there was no indication of a dose response relationship. The effect size (ES) after exclusion of suboptimal doses was of a more respectable magnitude (0.5) than that usually attributed to the antidepressant effect of the SSRIs. In conclusion, the observation that low doses are less effective than higher ones challenges the oft-cited view that the effect of the SSRIs is not dose-dependent and hence not caused by a specific, pharmacological antidepressant action. Moreover, we suggest that inclusion of suboptimal doses in previous meta-analyses has led to an underestimation of the efficacy of these drugs. PMID- 27271862 TI - Persistence of Neonatal Brachial Plexus Palsy Associated with Maternally Reported Route of Delivery: Review of 387 Cases (Podcast). PMID- 27271861 TI - Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder. AB - Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white matter networks compared with MDD patients without suicidal ideation. Participants consisted of 24 patients with MDD and suicidal ideation, 25 age- and gender-matched MDD patients without suicidal ideation and 31 healthy subjects. A network-based statistics (NBS) and a graph theoretical analysis were performed to assess differences in the inter-regional connectivity. Diffusion tensor imaging (DTI) was performed to assess topological changes according to suicidal ideation in MDD patients. The Scale for Suicide Ideation (SSI) and the Korean version of the Barrett Impulsiveness Scale (BIS) were used to assess the severity of suicidal ideation and impulsivity, respectively. Reduced structural connectivity in a characterized subnetwork was found in patients with MDD and suicidal ideation by utilizing NBS analysis. The subnetwork included the regions of the frontosubcortical circuits and the regions involved in executive function in the left hemisphere (rostral middle frontal, pallidum, superior parietal, frontal pole, caudate, putamen and thalamus). The graph theoretical analysis demonstrated that network measures of the left rostral middle frontal had a significant positive correlation with severity of SSI (r=0.59, P=0.02) and BIS (r=0.59, P=0.01). The total edge strength that was significantly associated with suicidal ideation did not differ between MDD patients without suicidal ideation and healthy subjects. Our findings suggest that the reduced frontosubcortical circuit of structural connectivity, which includes regions associated with executive function and impulsivity, appears to have a role in the emergence of suicidal ideation in MDD patients. PMID- 27271863 TI - The improved biological response of shark tooth bioapatites in a comparative in vitro study with synthetic and bovine bone grafts. AB - Autologous bone is considered to be the gold standard for bone tissue regeneration, providing more highly efficient functional responses compared to synthetic materials, and avoiding the rejection risks of allogenic grafts. However, it presents limitations for certain types of surgery due to its high resorption levels and donor site morbidity. Different biphasic synthetic composites, based onnon-apatitic calcium phosphates enriched with apatitic phases such as hydroxyapatite, and bioderived bone grafts of bovine and porcine origin are proposed as lower resorption materials due to their higher crystalline structure. The present work proposes two new sources of bioapatites for bone filler applications obtained from the dentine and enameloid of shark teeth, respectively. These bioapatites each present a characteristic apatite-based composition and additional enrichments of specific trace elements, such as magnesium and fluorine, with proven roles in bone metabolism. Their processing and physicochemical characterization (SEM, FT-Raman and XRD) is presented, together with an in vitro evaluation of osteogenic activity compared to a commercial bovine mineralized matrix and synthetic HA/beta TCP grafts. The results proved the globular morphology (0.5-1.5 MUm) and porosity (~50 MUm and ~0.5-1 MUm) of shark dentine bioapatites with biphasic composition: apatitic (hydroxyapatite and apatite-(CaF)), non-apatitic (whitlockite), and an apatitic phase (fluorapatite), organized in oriented crystals in enameloid bioapatites. An evaluation of the pre-osteoblast MC3T3-E1 morphology revealed the colonization of pores in dentine bioapatites and an aligned cell growth in the oriented enameloid crystals. A higher proliferation (p < 0.01) was detected at up to 21 d in both the shark bioapatites and synthetic biphasic graft with respect to the bovine mineralized matrix. Finally, the great potential of porous biphasic dentine bioapatites enriched with Mg and the aligned fluorapatite crystals of enameloid bioapatites in promoting greater osteogenic activity was confirmed with a significantly increased ALP synthesis (p < 0.01) compared to the commercial grafts. PMID- 27271864 TI - Synthesis of eucalyptus/tea tree oil absorbed biphasic calcium phosphate-PVDF polymer nanocomposite films: a surface active antimicrobial system for biomedical application. AB - A biocompatible poly(vinylidene) difluoride (PVDF) based film has been prepared by in situ precipitation of calcium phosphate precursors. Such films were surface absorbed with two essential oils namely eucalyptus and tea tree oil. Physico chemical characterization of the composite film revealed excellent stability of the film with 10% loading of oils in the PVDF matrix. XRD, FTIR and FESEM measurements confirmed the presence of hydroxyapatite and octacalcium phosphate in the PVDF matrix which showed predominantly beta phase. Strong bactericidal activity was observed with very low minimum bactericidal concentration (MBC) values on both E. coli and S. aureus. The composite films also resisted biofilm formation as observed by FESEM. The release of essential oils from the film showed an initial burst followed by a very slow release over a period of 24 hours. Antibacterial action of the film was found to be primarily due to the action of essential oils which resulted in leakage of vital fluids from the microorganisms. Both necrotic and apoptotic morphologies were observed in bacterial cells. Biocompatibility studies with the composite films showed negligible cytotoxicity to mouse mesenchymal and myoblast cells at MBC concentration. PMID- 27271865 TI - Effects of extremely low frequency magnetic field on production of mannatide by alpha-hemolytic Streptococcus. AB - The effect of the extremely low frequency magnetic field (ELF-MF) on biomass and mannatide production by alpha-hemolytic Streptococcus in liquid-state fermentation culture medium was studied during shake flask culture. Magnetic field (MF) inductions, exposure times, and exposure periods varied in a range of 0-1.5 mT, 0-16 h, and six periods of incubation time, respectively. Results showed both biomass and mannatide production increased significantly at MF induction 0.4, 0.6, and 0.9 mT and decreased at both 1.2 and 1.5 mT. Biomass increased by exposure for initial and middle stages of fermentation. Mannatide production increased significantly at 4-8, 8-12, and 17-21 h. Peak yield of biomass and mannatide production increased by 10.7% and 14.0% at 25 and 27 h of incubation at 0.6 mT MF induction and exposure to 8-12 h of incubation time, compared with the control experiment, respectively. ELF-MF could also enhance the growth rate and mannatide production rate of alpha-hemolytic Streptococcus. However, ELF-MF did not alter alpha-hemolytic Streptococcus cell growth and mannatide metabolizing regulation or fermentation pattern. Mannatide production was not associated with cellular growth but rather only partially associated. Bioelectromagnetics. 37:331-337, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27271866 TI - Understanding the full breadth of cancer-related patient costs in Ontario: a qualitative exploration. AB - OBJECTIVE: This research informs existing work by examining the full scope of out of-pocket costs and lost income, patients' private insurance behaviors, and their overall management of finances during their cancer treatment. The intent was to gain a deeper understanding of patient circumstances and the related costs. METHODS: Participant qualitative interviews were conducted in person during outpatient clinic visits or by telephone and were recorded between June 2011 and July 2012. Interviews were transcribed verbatim and subjected to a descriptive qualitative analysis. The research team collaborated early in the process (after three subjects were enrolled) to develop a preliminary coding framework. The coding framework was modified to incorporate additional emerging content until saturation of data was evident. Transcripts were coded using the qualitative software NVivo version 9.0. RESULTS: Fifteen patients agreed to participate in the study and 14 completed the interview (seven breast, three colorectal, two lung, and two prostate). Consistent with existing published work, participants expressed concerns regarding expenses related to medications, complementary/alternative medicines, devices, parking and travel. These concerns were exacerbated if patients did not have insurance or lost insurance coverage due to loss of work. Although many acknowledged in hindsight that additional insurance would have helped, they also recognized that at the time of their diagnoses, it was not a viable option. Previously unidentified categorical costs identified in this study included modifications to housing arrangements or renovations, special clothing, fitness costs and the impact of an altered diet. CONCLUSION: We confirmed the results of earlier Canadian quantitative work. Additionally, cost categories not previously explored were identified, which will facilitate the development of an improved and more comprehensive quantitative questionnaire for future research. Many patients indicated that supplemental health insurance would have made their cancer journey less stressful, highlighting existing gaps in the government funded health care system. PMID- 27271867 TI - Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ). AB - BACKGROUND: In malignant glioma (MG) patients undergoing radiation therapy (RT) with concomitant temozolomide, chemoradiation-induced nausea and vomiting (cRINV) degrades quality of life (QoL) and reduces treatment adherence, which thereby potentially compromises cancer control. METHODS: We conducted a 6-week phase II single-arm trial of PAL, a second-generation 5-HT3RA antiemetic, for cRINV prevention in MG patients receiving radiation therapy (RT; 54-60 Gy) and concomitant daily temozolomide (TMZ; 75 mg/m(2)/dX42d). Each week before radiation, patients received single-dose palonosetron (PAL) 0.25 mg IV (total = 6 doses). With safety/tolerability as the primary endpoint, the study was designed to differentiate between toxicity rates of 25 % (unacceptable) and 10 % (acceptable) toxicity rates. Secondary endpoints included the percentage of patients achieving cRINV complete response (CR: no emesis or rescue antiemetic) and QoL. Patients reported adverse effects in Common Toxicity Criteria for Adverse Events diaries; recorded vomiting, nausea, and rescue medication use in diaries (which were used to assess cRINV-CR); and reported QoL 4 days/week using the Modified Functional Living Index-Emesis (M-FLIE) and Osoba nausea and vomiting/retching modules. RESULTS: We enrolled 38 patients (mean age 59 years, 55 % female, 95 % white, 68 % used oral corticosteroids, 76 % reported low alcohol use). Four patients (10.5 %) experienced unacceptable treatment-related toxicity, defined as any grade 3, 4, or 5 non-hematologic toxicity. M-FLIE and Osoba scores showed no evidence of treatment impact on QoL. Overall, cRINV-CR rates for 6 weeks ranged from 67-79 %. CONCLUSION: Single-dose weekly PAL is a safe and tolerable antiemetic for cRINV prevention in MG patients receiving standard RT and concomitant TMZ. PMID- 27271868 TI - Prevalence and risk factors associated with pain 21 months following surgery for breast cancer. AB - PURPOSE: This study investigated (1) the prevalence of pain following breast cancer treatment including moderate-to-severe persistent pain and (2) the association of risk factors, present 1 month following surgery, with pain at 21 months following surgery. This information may aid the development of clinical guidelines for early pain assessment and intervention in this population. METHODS: This study was a retrospective analysis of core and breast modules of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire from 121 participants with early breast cancer. The relationships between potential risk factors (subscales derived from the EORTC), measured within 1 month following surgery, and pain at 21 months following surgery were analysed using univariable and multi-variable logistic regression. RESULTS: At 21 months following surgery, 46.3 % of participants reported pain, with 24 % categorised as having moderate or severe pain. Prevalence of pain was similar between those who underwent axillary lymph node dissection versus biopsy. Univariate logistic regression identified baseline pain (odds ratio (95 % CI): 2.7 (1.1 to 6.4)); baseline arm symptoms (11.2 (1.4 to 89.8)); emotional function (0.4 (0.1 to 0.8)) and insomnia (2.3 (1.1 to 4.7) as significantly associated with pain at 21 months. In multi-variable analysis, two factors were independently associated with pain at 21 months-baseline arm symptoms and emotional subscale scores. CONCLUSION: Pain is a significant problem following breast cancer treatment in both the early post-operative period and months following surgery. Risk factors for pain at long-term follow-up included arm symptoms and higher emotional subscale scores at baseline. PMID- 27271869 TI - Spectroscopic Raman characterization of rutherfordine: a combined DFT and experimental study. AB - A rutherfordine mineral was studied by means of Raman spectroscopy combined with first principle calculations based on the density functional theory (DFT) method. The pseudopotential of a uranium atom was generated and its performance was evaluated for a series of uranium-containing minerals. The structure of rutherfordine was determined for two symmetries (Pmmn and Imm2) and the resulting lattice parameters, bond lengths, bond angles, and X-ray powder diffractogram were found to be in very good agreement with experimental values. The Raman spectrum was experimentally determined in the range 0-1700 cm(-1) and calculated using density functional perturbation theory. The non-scaled theoretical wavenumbers also agreed with the experimental values, and therefore a detailed interpretation of the theoretical spectra allowed us to assign the Raman bands found in the experimental spectrum. PMID- 27271870 TI - Retention of the spacing effect with mental practice in hemiparetic stroke. AB - Mental practice (MP) is a promising adjuvant to physical practice that involves many of the same mechanisms and takes on many of the same properties as physical practice. This study compared efficacy of a "massed" MP regimen versus a "distributed" MP regimen on upper extremity (UE) motor impairment and functional limitation. Twenty-seven chronic stroke survivors were administered the UE section of the Fugl-Meyer (FM) and Action Research Arm Test (ARAT), followed by standardized physical practice and MP regimens. One group was administered "massed" MP (60 min of MP during a single daily session) and a second group administered distributed MP (20 min of MP occurring three times/day). After intervention, changes in FM and ARAT scores of subjects in the distributed condition were significantly higher than those of subjects in the massed condition (FM 3.65, 95 % CI 0.82-6.49, p value = 0.01; ARAT 3.95, 95 % CI 1.24 6.67, p value = 0.006). Likewise, at POST 3, subjects in the distributed group showed significantly higher change in ARAT scores (ARAT 4.90, 95 % CI 0.57-9.22, p value = 0.03); the change in FM scores at POST 3 was 3.18 points higher among subjects in the distributed condition, but only approached significance (95 % CI 1.27 to 7.63, p value = 0.15). Results suggest that a distributed MP schedule is more efficacious in bringing about paretic UE changes than a massed practice schedule, especially in terms of reducing UE functional limitation. PMID- 27271871 TI - The buzz-lag effect. AB - In the flash-lag illusion, a brief visual flash and a moving object presented at the same location appear to be offset with the flash trailing the moving object. A considerable amount of studies investigated the visual flash-lag effect, and flash-lag-like effects have also been observed in audition, and cross-modally between vision and audition. In the present study, we investigate whether a similar effect can also be observed when using only haptic stimuli. A fast vibration (or buzz, lasting less than 20 ms) was applied to the moving finger of the observers and employed as a "haptic flash." Participants performed a two alternative forced-choice (2AFC) task where they had to judge whether the moving finger was located to the right or to the left of the stationary finger at the time of the buzz. We used two different movement velocities (Slow and Fast conditions). We found that the moving finger was systematically misperceived to be ahead of the stationary finger when the two were physically aligned. This result can be interpreted as a purely haptic analogue of the flash-lag effect, which we refer to as "buzz-lag effect." The buzz-lag effect can be well accounted for by the temporal-sampling explanation of flash-lag-like effects. PMID- 27271872 TI - Effects of Treatment of Asymptomatic Hyperuricemia on Graft Survival and Mortality in Kidney Transplant Recipients. AB - BACKGROUND Hyperuricemia is very common after renal transplantation. It is associated with an increased risk of cardiovascular events and graft loss. To date, however, treatment is only recommended in symptomatic disease. MATERIAL AND METHODS We included 503 adult patients who underwent kidney transplantation at the Charite-Universitatsmedizin Berlin in this retrospective study. Patients were followed up for up to 120 months. All-cause mortality, graft survival, changes in level of serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were analyzed. RESULTS At 12 months post-transplantation, 225 patients had a serum uric acid (SUA) level >7 mg/dl: 52 patients were treated with allopurinol, 37 with benzbromarone, and 136 patients received no medication for hyperuricemia (control). At 12 months, eGFR did not differ between groups (p=0.15) but treated patients had higher SUA levels (p<0.001) compared to the control group. SUA lowering treatment was associated with a lower risk of all-cause mortality (p=0.013) and graft loss (p=0.014) compared to controls. At 120 months, patients in the treatment group had lower SUA levels (p=0.001) and higher eGFR (p<0.001) compared to the control group. CONCLUSIONS Treatment of asymptomatic hyperuricemia was associated with a substantial benefit in patient and graft survival. PMID- 27271873 TI - Editorial. PMID- 27271874 TI - Erratum. PMID- 27271875 TI - An NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles for tumor targeted drug delivery in vitro and in vivo. AB - The synthesis and characterization of an NAD(P)H: quinone oxidoreductase 1 (NQO1) enzyme responsive nanocarrier based on mesoporous silica nanoparticles (MSNPs) for on-command delivery applications has been described in this paper. Gatekeeping of MSNPs is achieved by the integration of mechanically interlocked rotaxane nanovalves on the surface of MSNPs. The rotaxane nanovalve system is composed of a linear stalk anchoring on the surface of MSNPs, an alpha cyclodextrin ring that encircles it and locks the payload "cargo" molecules in the mesopores, and a benzoquinone stopper incorporated at the end of the stalk. The gate opening and controlled release of the cargo are triggered by cleavage of the benzoquinone stopper using an endogenous NQO1 enzyme. In addition to having efficient drug loading and controlled release mechanisms, this smart biocompatible carrier system showed obvious uptake and consequent release of the drug in tumor cells, could selectively induce the tumor cell death and enhance the capability of inhibition of tumor growth in vivo. The controlled drug delivery system demonstrated its use as a potential theranostic material. PMID- 27271876 TI - A Functionally Superior Second-Generation Vector Expressing an Aurora Kinase-A Specific T-Cell Receptor for Anti-Leukaemia Adoptive Immunotherapy. AB - Aurora Kinase A is a cancer-associated protein normally involved in the regulation of mitosis. Being over-expressed in a range of cancers, it is a suitable target for cell-based immunotherapy. Gene transfer of T-cell receptor sequences cognisant of HLA-A*0201-restricted Aurora Kinase A antigen has previously been shown to transfer specific immunoreactivity against the target peptide in a Human Lymphocyte Antigen-restricted manner. While T cell receptor gene-transfer has great potential in overcoming the difficulties of isolating and expanding tumour-reactive lymphocytes from a patient's own cells, one hurdle is potential mispairing and competition between exogenous and endogenous T cell receptor chains. We have used a retroviral vector design bearing a short interfering RNA that downregulates endogenous T cell receptor chains, without affecting expression of the transgenic T cell receptor sequences. The T cell receptor expression cassette also includes a 2A self-cleaving peptide, resulting in equimolar expression of the T cell receptor alpha and beta chains, further enhancing formation of the desired T cell receptor. Via a simple, modular cloning method, we have cloned the alpha and beta chains of the anti-Aurora Kinase A reactive T cell receptor into this 'siTCR' vector. We then compared the activity of this vector against the original, 'conventional' vector across a panel of assays. T cell receptors expressed from the siTCR-vector retained the cytotoxic functionality of the original vector, with evidence of reduced off-target reactivity. The rate of expression of correctly-formed T cell receptors was superior using the siTCR design, and this was achieved at lower vector copy numbers. Maintaining T cell receptor efficacy with a reduced vector copy number reduces the risk of genotoxicity. The siTCR design also reduces the risk of mispairing and cross-reactivity, while increasing the functional titre. Such improvements in the safety of T cell receptor gene-transfer will be crucial for clinical applications of this technology. PMID- 27271877 TI - Organizing empyema induced in mice by Streptococcus pneumoniae: effects of plasminogen activator inhibitor-1 deficiency. AB - BACKGROUND: Pleural infection affects about 65,000 patients annually in the US and UK. In this and other forms of pleural injury, mesothelial cells (PMCs) undergo a process called mesothelial (Meso) mesenchymal transition (MT), by which PMCs acquire a profibrogenic phenotype with increased expression of alpha-smooth muscle actin (alpha-SMA) and matrix proteins. MesoMT thereby contributes to pleural organization with fibrosis and lung restriction. Current murine empyema models are characterized by early mortality, limiting analysis of the pathogenesis of pleural organization and mechanisms that promote MesoMT after infection. METHODS: A new murine empyema model was generated in C57BL/6 J mice by intrapleural delivery of Streptococcus pneumoniae (D39, 3 * 10(7)-5 * 10(9) cfu) to enable use of genetically manipulated animals. CT-scanning and pulmonary function tests were used to characterize the physiologic consequences of organizing empyema. Histology, immunohistochemistry, and immunofluorescence were used to assess pleural injury. ELISA, cytokine array and western analyses were used to assess pleural fluid mediators and markers of MesoMT in primary PMCs. RESULTS: Induction of empyema was done through intranasal or intrapleural delivery of S. pneumoniae. Intranasal delivery impaired lung compliance (p < 0.05) and reduced lung volume (p < 0.05) by 7 days, but failed to reliably induce empyema and was characterized by unacceptable mortality. Intrapleural delivery of S. pneumoniae induced empyema by 24 h with lung restriction and development of pleural fibrosis which persisted for up to 14 days. Markers of MesoMT were increased in the visceral pleura of S. pneumoniae infected mice. KC, IL-17A, MIP 1beta, MCP-1, PGE2 and plasmin activity were increased in pleural lavage of infected mice at 7 days. PAI-1(-/-) mice died within 4 days, had increased pleural inflammation and higher PGE2 levels than WT mice. PGE2 was induced in primary PMCs by uPA and plasmin and induced markers of MesoMT. CONCLUSION: To our knowledge, this is the first murine model of subacute, organizing empyema. The model can be used to identify factors that, like PAI-1 deficiency, alter outcomes and dissect their contribution to pleural organization, rind formation and lung restriction. PMID- 27271879 TI - Building the basis for proteomics in personalized medicine for targeted treatment. PMID- 27271878 TI - Diagnostic yield of array CGH in patients with autism spectrum disorder in Hong Kong. AB - BACKGROUND: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNV) and it is advocated to be the first tier genetic testing for patients with autism spectrum disorder (ASD). In this regard, diagnostic yield of array comparative genomic hybridization (CGH) for ASD patients is determined in a cohort of Chinese patients in Hong Kong. METHODS: A combined adult and paediatric cohort of 68 Chinese ASD patients (41 patients in adult group and 27 patients in paediatric group). The genomic DNA extracted from blood samples were analysed by array CGH using NimbleGen CGX-135K oligonucleotide array. RESULTS: We identified 15 CNV and eight of them were clinically significant. The overall diagnostic yield was 11.8 %. Five clinically significant CNV were detected in the adult group and three were in the paediatric group, providing diagnostic yields of 12.2 and 11.1 % respectively. The most frequently detected CNV was 16p13.11 duplications which were present in 4 patients (5.9 % of the cohort). CONCLUSIONS: In this study, a satisfactory diagnostic yield of array CGH was demonstrated in a Chinese ASD patient cohort which supported the clinical usefulness of array CGH as the first line testing of ASD in Hong Kong. PMID- 27271881 TI - It's Harder to Break a Relationship When you Commit Long. AB - Past research has produced evidence that parsing commitments strengthen over the processing of additional linguistic elements that are consistent with the commitments and undoing strong commitments takes more time than undoing weak commitments. It remains unclear, however, whether this so-called digging-in effect is exclusively due to the length of an ambiguous region or at least partly to the extra cost of processing these additional phrases. The current study addressed this issue by testing Japanese relative clause structure, where lexical content and sentence meaning were controlled for. The results showed evidence for a digging-in effect reflecting the strengthened commitment to an incorrect analysis caused by the processing of additional adjuncts. Our study provides strong support for the dynamical, self-organizing models of sentence processing but poses a problem for other models including serial two-stage models as well as frequency-based probabilistic models such as the surprisal theory. PMID- 27271882 TI - "The Talk:" Discussing Hospice Care. AB - Referral of advanced cancer patients for hospice care is of growing importance for oncologists. Hospice care is high quality and high value care that can benefit the patient and family's experience of living and dying with terminal cancer. We are challenged to become a part of the shift from hospice meaning "giving up" to hospice meaning "giving more, but differently." The purpose of this report is to frame a communication approach that any oncologist can incorporate into his or her practice that will facilitate the timely referral of appropriate patients for hospice care. Combining the strengths of oncology, palliative, and hospice providers in a complementary fashion allows us to serve patients and their families in the most meaningful way. PMID- 27271883 TI - Pancreatitis in Children. AB - Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune]. PMID- 27271884 TI - Scrub Typhus Causing Unilateral Optic Neuritis. PMID- 27271885 TI - Tattoos, Beer, and Bow Ties: The Limits of Professionalism in Medicine. PMID- 27271886 TI - Rotatable Small Permanent Magnet Array for Ultra-Low Field Nuclear Magnetic Resonance Instrumentation: A Concept Study. AB - OBJECT: We studied the feasibility of generating the variable magnetic fields required for ultra-low field nuclear magnetic resonance relaxometry with dynamically adjustable permanent magnets. Our motivation was to substitute traditional electromagnets by distributed permanent magnets, increasing system portability. MATERIALS AND METHODS: The finite element method (COMSOL(r)) was employed for the numerical study of a small permanent magnet array to calculate achievable magnetic field strength, homogeneity, switching time and magnetic forces. A manually operated prototype was simulated and constructed to validate the numerical approach and to verify the generated magnetic field. RESULTS: A concentric small permanent magnet array can be used to generate strong sample pre polarisation and variable measurement fields for ultra-low field relaxometry via simple prescribed magnet rotations. Using the array, it is possible to achieve a pre-polarisation field strength above 100 mT and variable measurement fields ranging from 20-50 MUT with 200 ppm absolute field homogeneity within a field-of view of 5 x 5 x 5 cubic centimetres. CONCLUSIONS: A dynamic small permanent magnet array can generate multiple highly homogeneous magnetic fields required in ultra-low field nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) instruments. This design can significantly reduce the volume and energy requirements of traditional systems based on electromagnets, improving portability considerably. PMID- 27271887 TI - Inserting and holding the Bakri balloon in the uterus in a patient with cervical cerclage already placed: some techniques. PMID- 27271888 TI - Organocatalytic asymmetric addition of alcohols to cyclic trifluoromethyl ketimines: highly enantioselective synthesis of chiral N,O-ketals. AB - A highly enantioselective addition of alcohols to cyclic trifluoromethyl ketimines is developed catalyzed by quinine-thiourea, giving biologically interesting N,O-ketals in up to 99% yield and 96% ee. PMID- 27271889 TI - Study of a simple model for the transition between the ballistic and the diffusive regimes in diffusive media. AB - A Monte Carlo simulation was utilized to investigate a simple model for the transition between the ballistic and the diffusive regimes in diffusive media. The simulation focuses on the propagation of visible and near-infrared light in biological tissues. This research has mainly two findings: (1) the transition can be described, as was found experimentally, with good accuracy by only two terms (ballistic and diffusive). (2) The model can be utilized for cases where the absorption coefficient is not negligible compared to the scattering coefficient by adding a power-law prefactor to the diffusive term. PMID- 27271890 TI - In Situ Assays of Chemotropism During Yeast Mating. AB - Virtually all eukaryotic cells can grow in a polarized fashion in response to external signals. Cells can respond to gradients of chemoattractants or chemorepellents by directional growth, a process referred to as chemotropism. The budding yeast Saccharomyces cerevisiae undergoes chemotropic growth during mating, in which two haploid cells of opposite mating type grow towards one another. Mating pheromone gradients are essential for efficient mating in yeast and different yeast mutants are defective in chemotropism. Two methods of assessing the ability of yeast strains to respond to pheromone gradients are presented here. PMID- 27271891 TI - Imaging Polarization in Budding Yeast. AB - We describe methods for live-cell imaging of yeast cells that we have exploited to image yeast polarity establishment. As a rare event occurring on a fast time scale, imaging polarization involves a trade-off between spatiotemporal resolution and long-term imaging without excessive phototoxicity. By synchronizing cells in a way that increases resistance to photodamage, we discovered unexpected aspects of polarization including transient intermediates with more than one polarity cluster, oscillatory clustering of polarity factors, and mobile "wandering" polarity sites. PMID- 27271892 TI - Migration of Dictyostelium discoideum to the Chemoattractant Folic Acid. AB - Dictyostelium discoideum can be grown axenically in a cultured media or in the presence of a natural food source, such as the bacterium Klebsiella aerogenes (KA). Here we describe the advantages and methods for growing D. discoideum on a bacterial lawn for several processes studied using this model system. When grown on a bacterial lawn, D. discoideum show positive chemotaxis towards folic acid (FA). While these vegetative cells are highly unpolarized, it has been shown that the signaling and cytoskeletal molecules regulating the directed migration of these cells are homologous to those seen in the motility of polarized cells in response to the chemoattractant cyclic adenosine monophosphate (cAMP). Growing D. discoideum on KA stimulates chemotactic responsiveness to FA. A major advantage of performing FA-mediated chemotaxis is that it does not require expression of the cAMP developmental program and therefore has the potential to identify mutants that are purely unresponsive to chemoattractant gradients. The cAMP mediated chemotaxis can appear to fail when cells are developmentally delayed or do not up-regulate genes needed for cAMP-mediated migration. In addition to providing robust chemotaxis to FA, cells grown on bacterial lawns are highly resistant to light damage during fluorescence microscopy. This resistance to light damage could be exploited to better understand other biological processes such as phagocytosis or cytokinesis. The cell cycle is also shortened when cells are grown in the presence of KA, so the chances of seeing a mitotic event increases. PMID- 27271893 TI - Mitochondrial Stress Tests Using Seahorse Respirometry on Intact Dictyostelium discoideum Cells. AB - Mitochondria not only play a critical and central role in providing metabolic energy to the cell but are also integral to the other cellular processes such as modulation of various signaling pathways. These pathways affect many aspects of cell physiology, including cell movement, growth, division, differentiation, and death. Mitochondrial dysfunction which affects mitochondrial bioenergetics and causes oxidative phosphorylation defects can thus lead to altered cellular physiology and manifest in disease. The assessment of the mitochondrial bioenergetics can thus provide valuable insights into the physiological state, and the alterations to the state of the cells. Here, we describe a method to successfully use the Seahorse XF(e)24 Extracellular Flux Analyzer to assess the mitochondrial respirometry of the cellular slime mold Dictyostelium discoideum. PMID- 27271894 TI - Studying Chemoattractant Signal Transduction Dynamics in Dictyostelium by BRET. AB - Understanding the dynamics of chemoattractant signaling is key to our understanding of the mechanisms underlying the directed migration of cells, including that of neutrophils to sites of infections and of cancer cells during metastasis. A model frequently used for deciphering chemoattractant signal transduction is the social amoeba Dictyostelium discoideum. However, the methods available to quantitatively measure chemotactic signaling are limited. Here, we describe a protocol to quantitatively study chemoattractant signal transduction in Dictyostelium by monitoring protein-protein interactions and conformational changes using Bioluminescence Resonance Energy Transfer (BRET). PMID- 27271895 TI - Wave Patterns in Cell Membrane and Actin Cortex Uncoupled from Chemotactic Signals. AB - When cells of Dictyostelium discoideum orientate in a gradient of chemoattractant, they are polarized into a protruding front pointing toward the source of attractant, and into a retracting tail. Under the control of chemotactic signal inputs, Ras is activated and PIP3 is synthesized at the front, while the PIP3-degrading phosphatase PTEN decorates the tail region. As a result of signal transduction, actin filaments assemble at the front into dendritic structures associated with the Arp2/3 complex, in contrast to the tail region where a loose actin meshwork is associated with myosin-II and cortexillin, an antiparallel actin-bundling protein. In axenically growing strains of D. discoideum, wave patterns built by the same components evolve in the absence of any external signal input. Since these autonomously generated patterns are constrained to the plane of the substrate-attached cell surface, they are optimally suited to the optical analysis of state transitions between front-like and tail-like states of the membrane and the actin cortex. Here, we describe imaging techniques using fluorescent proteins to probe for the state of the membrane, the reorganization of the actin network, and the dynamics of wave patterns. PMID- 27271896 TI - Chemotactic Blebbing in Dictyostelium Cells. AB - Many researchers use the social amoeba Dictyostelium discoideum as a model organism to study various aspects of the eukaryotic cell chemotaxis. Traditionally, Dictyostelium chemotaxis is considered to be driven mainly by branched F-actin polymerization. However, recently it has become evident that Dictyostelium, as well as many other eukaryotic cells, can also employ intracellular hydrostatic pressure to generate force for migration. This process results in the projection of hemispherical plasma membrane protrusions, called blebs, that can be controlled by chemotactic signaling.Here we describe two methods to study chemotactic blebbing in Dictyostelium cells and to analyze the intensity of the blebbing response in various strains and under different conditions. The first of these methods-the cyclic-AMP shock assay-allows one to quantify the global blebbing response of cells to a uniform chemoattractant stimulation. The second one-the under-agarose migration assay-induces directional blebbing in cells moving in a gradient of chemoattractant. In this assay, the cells can be switched from a predominantly F-actin-driven mode of motility to a bleb-driven chemotaxis, allowing one to compare the efficiency of both modes and explore the molecular machinery controlling chemotactic blebbing. PMID- 27271897 TI - Dissecting Spatial and Temporal Sensing in Dictyostelium Chemotaxis Using a Wave Gradient Generator. AB - External cues that dictate the direction of cell migration are likely dynamic during many biological processes such as embryonic development and wound healing. Until recently, how cells integrate spatial and temporal information to determine the direction of migration has remained elusive. In Dictyostelium discoideum, the chemoattractant cAMP that directs cell aggregation propagates as periodic waves. In light of the fact that any temporally evolving complex signals, in principle, can be expressed as a sum of sinusoidal functions with various frequencies, the Dictyostelium system serves as a minimal example, where the dynamic signal is in the simplest form of near sinusoidal wave with one dominant frequency. Here, we describe a method to emulate the traveling waves in a fluidics device. The text provides step-by-step instructions on the device setup and describes ways to analyze the acquired data. These include quantification of membrane translocation of fluorescently labeled proteins in individual Dictyostelium cells and estimation of exogenous cAMP profiles. The described approach has already helped decipher spatial and temporal aspects of chemotactic sensing in Dictyostelium. More specifically, it allowed one to discriminate the temporal and the spatial sensing aspects of directional sensing. With some modifications, one should be able to implement similar analysis in other cell types. PMID- 27271899 TI - Identification of Associated Proteins by Immunoprecipitation and Mass Spectrometry Analysis. AB - Protein-protein interactions play central roles in intercellular and intracellular signal transduction. Impairment of protein-protein interactions causes many diseases such as cancer, cardiomyopathies, diabetes, microbial infections, and genetic and neurodegenerative disorders. Immunoprecipitation is a technique in which a target protein of interest bound by an antibody is used to pull down the protein complex out of cell lysates, which can be identified by mass spectrometry. Here, we describe the protocol to immunoprecipitate and identify the components of the protein complexes of ElmoE in Dictyostelium discoideum cells. PMID- 27271898 TI - Employing Dictyostelium as an Advantageous 3Rs Model for Pharmacogenetic Research. AB - Increasing concern regarding the use of animals in research has triggered a growing need for non-animal research models in a range of fields. The development of 3Rs (replacement, refinement, and reduction) approaches in research, to reduce the reliance on the use of animal tissue and whole-animal experiments, has recently included the use of Dictyostelium. In addition to not feeling pain and thus being relatively free of ethical constraints, Dictyostelium provides a range of distinct methodological advantages for researchers that has led to a number of breakthroughs. These methodologies include using cell behavior (cell movement and shape) as a rapid indicator of sensitivity to poorly characterized medicines, natural products, and other chemicals to help understand the molecular mechanism of action of compounds. Here, we outline a general approach to employing Dictyostelium as a 3Rs research model, using cell behavior as a readout to better understand how compounds, such as the active ingredient in chilli peppers, capsaicin, function at a cellular level. This chapter helps scientists unfamiliar with Dictyostelium to rapidly employ it as an advantageous model system for research, to reduce the use of animals in research, and to make paradigm shift advances in our understanding of biological chemistry. PMID- 27271900 TI - Biochemical Responses to Chemically Distinct Chemoattractants During the Growth and Development of Dictyostelium. AB - Dictyostelium discoideum has proven an excellent model for the study of eukaryotic chemotaxis. During growth in its native environment, Dictyostelium phagocytose bacteria and fungi for primary nutrient capture. Growing Dictyostelium can detect these nutrient sources through chemotaxis toward the metabolic by-product folate. Although Dictyostelium grow as individual cells, nutrient depletion induces a multicellular development program and a separate chemotactic response pathway. During development, Dictyostelium synthesize and secrete cAMP, which serves as a chemoattractant to mobilize and coordinate cells for multicellular formation and development. Separate classes of GPCRs and Galpha proteins mediate chemotactic signaling to the chemically distinct ligands. We discuss common and separate component responses of Dictyostelium to folate and cAMP during growth and development, and the advantages and disadvantages for each. As examples, we present biochemical assays to characterize the chemoattractant-induced kinase activations of mTORC2 and the ERKs. PMID- 27271901 TI - Live Imaging of Border Cell Migration in Drosophila. AB - Border cells are a cluster of cells that migrate from the anterior tip of the Drosophila egg chamber to the border of the oocyte in stage 9. They serve as a useful model to study collective cell migration in a native tissue environment. Here we describe a protocol for preparing ex vivo egg chamber cultures from transgenic flies expressing fluorescent proteins in the border cells, and using confocal microscopy to take a multi-positional time-lapse movie. We include an image analysis method for tracking border cell cluster dynamics as well as tracking individual cell movements. PMID- 27271902 TI - shRNA-Induced Gene Knockdown In Vivo to Investigate Neutrophil Function. AB - To silence genes in neutrophils efficiently, we exploited the RNA interference and developed an shRNA-based gene knockdown technique. This method involves transfection of mouse bone marrow-derived hematopoietic stem cells with retroviral vector carrying shRNA directed at a specific gene. Transfected stem cells are then transplanted into irradiated wild-type mice. After engraftment of stem cells, the transplanted mice have two sets of circulating neutrophils. One set has a gene of interest knocked down while the other set has full complement of expressed genes. This efficient technique provides a unique way to directly compare the response of neutrophils with a knocked-down gene to that of neutrophils with the full complement of expressed genes in the same environment. PMID- 27271903 TI - Studying Neutrophil Migration In Vivo Using Adoptive Cell Transfer. AB - Adoptive cell transfer experiments can be used to study the roles of cell trafficking molecules on the migratory behavior of specific immune cell populations in vivo. Chemoattractants and their G protein-coupled seven transmembrane-spanning receptors regulate migration of cells in vivo, and dysregulated expression of chemoattractants and their receptors is implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. We have used adoptive neutrophil transfer to define the contributions of chemoattractant receptors, cytokines, and activation receptors expressed on neutrophils that critically regulate their entry into the inflamed joint. In this review, we describe the procedure of neutrophil adoptive transfer to study the influence of neutrophil-specific receptors or mediators upon the their recruitment into the joint using the K/BxN model of inflammatory arthritis as a model of how adoptive cell transfer studies can be used to study immune cell migration in vivo. PMID- 27271904 TI - Intravital Two-Photon Imaging of Lymphocytes Crossing High Endothelial Venules and Cortical Lymphatics in the Inguinal Lymph Node. AB - Lymphocyte recirculation through lymph nodes (LNs) requires their crossing of endothelial barriers present in blood vessels and lymphatics by means of chemoattractant-triggered cell migration. The chemoattractant-chemoattractant receptor axes that predominately govern the trafficking of lymphocytes into, and out of, LNs are CCL19/CCR7 and sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1PR1), respectively. Blood-borne lymphocytes downregulate S1PR1 and use CCR7 signaling to adhere to high endothelial venules (HEVs) for transmigration. During their LN residency, recirculating lymphocytes reacquire S1PR1 and attenuate their sensitivity to chemokines. Eventually lymphocytes exit the LN by entering the cortical or medullary lymphatics, a process that depends upon S1PR1 signaling. Upon entering into the lymph, lymphocytes lose their polarity, downregulate their sensitivity to S1P due to the high concentration of S1P, and upregulate their sensitivity to chemokines. However, many of the details of lymphocyte transmigration across endothelial barriers remain poorly understood. Intravital two-photon imaging with advanced microscope technologies not only allows the real time observation of immune cells in intact LN of a live mouse, but also provides a means to monitor the interactions between circulating lymphocytes and stromal barriers. Here, we describe procedures to visualize lymphocytes engaging and crossing HEVs, and approaching and crossing the cortical lymphatic endothelium to enter the efferent lymph in live mice. PMID- 27271905 TI - Flow Cytometry-Based Quantification of HIV-Induced T Cell Chemotactic Response. AB - The human immunodeficiency virus (HIV) infects blood CD4 T cells through binding to CD4 and the chemokine co-receptor, CXCR4 or CCR5. This viral binding to CXCR4 or CCR5 also triggers the activation of a variety of signaling molecules such as LIMK/cofilin and WAVE2/Arp2/3 to promote actin dynamics, which are necessary for viral nuclear migration and the latent infection of blood resting CD4 T cells. In this chapter, we describe the methods for quantification of HIV-induced actin polymerization and cofilin phosphorylation in human T cells using flow cytometry. PMID- 27271906 TI - Visualizing Cancer Cell Chemotaxis and Invasion in 2D and 3D. AB - We describe three chemotaxis assays-Insall chambers, circular invasion assays, and 3D organotypic assays-that are particularly appropriate for measuring migration of cancer cells in response to gradients of soluble attractants. Each assay has defined advantages, and together they provide the best possible quantitative assessment of cancer chemotaxis. PMID- 27271907 TI - 4D Tumorigenesis Model for Quantitating Coalescence, Directed Cell Motility and Chemotaxis, Identifying Unique Cell Behaviors, and Testing Anticancer Drugs. AB - A 4D high-resolution computer-assisted reconstruction and motion analysis system has been developed and applied to the long-term (14-30 days) analysis of cancer cells migrating and aggregating within a 3D matrix. 4D tumorigenesis models more closely approximate the tumor microenvironment than 2D substrates and, therefore, are improved tools for elucidating the interactions within the tumor microenvironment that promote growth and metastasis. The model we describe here can be used to analyze the growth of tumor cells, aggregate coalescence, directed cell motility and chemotaxis, matrix degradation, the effects of anticancer drugs, and the behavior of immune and endothelial cells mixed with cancer cells. The information given in this chapter is also intended to acquaint the reader with computer-assisted methods and algorithms that can be used for high resolution 3D reconstruction and quantitative motion analysis. PMID- 27271909 TI - Axon Guidance Studies Using a Microfluidics-Based Chemotropic Gradient Generator. AB - Microfluidics can be used to generate flow-driven gradients of chemotropic guidance cues with precisely controlled steepnesses for indefinite lengths of time. Neuronal cells grown in the presence of these gradients can be studied for their response to the effects exerted by the cues. Here we describe a polydimethylsiloxane (PDMS) microfluidics chamber capable of producing linear gradients of soluble factors, stable for at least 18 h, suitable for axon guidance studies. Using this device we demonstrate turning of superior cervical ganglion axons by gradients of nerve growth factor (NGF). The chamber produces robust gradients, is inexpensive to mass produce, can be mounted on a tissue culture dish or glass coverslip for long term time-lapse microscopy imaging, and is suitable for immunostaining. PMID- 27271908 TI - An Experimental Model for Simultaneous Study of Migration of Cell Fragments, Single Cells, and Cell Sheets. AB - Recent studies have demonstrated distinctive motility and responses to extracellular cues of cells in isolation, cells collectively in groups, and cell fragments. Here we provide a protocol for generating cell sheets, isolated cells, and cell fragments of keratocytes from zebrafish scales. The protocol starts with a comprehensive fish preparation, followed by critical steps for scale processing and subsequent cell sheet generation, single cell isolation, and cell fragment induction, which can be accomplished in just 3 days including a 36-48 h incubation time. Compared to other approaches that usually produce single cells only or together with either fragments or cell groups, this facile and reliable methodology allows generation of all three motile forms simultaneously. With the powerful genetics in zebrafish our model system offers a useful tool for comparison of the mechanisms by which cell sheets, single cells, and cell fragments respond to extracellular stimuli. PMID- 27271910 TI - Visualization of Actin Assembly and Filament Turnover by In Vitro Multicolor TIRF Microscopy. AB - In response to chemotactic signals, motile cells develop a single protruding front to persistently migrate in direction of the chemotactic gradient. The highly dynamic reorganization of the actin cytoskeleton is an essential part during this process and requires the precise interplay of various actin filament assembly factors and actin-binding proteins (ABPs). Although many ABPs have been implicated in cell migration, as yet only a few of them have been well characterized concerning their specific functions during actin network assembly and disassembly. In this chapter, we describe a versatile method that allows the direct visualization of the assembly of single actin filaments and higher structures in real time by in vitro total internal reflection fluorescence microscopy (TIRF-M) using purified and fluorescently labeled actin and ABPs. PMID- 27271912 TI - Fluorescence Readout of a Patch Clamped Membrane by Laser Scanning Microscopy. AB - In this chapter, we describe how to shield a patch of a cell membrane against extracellularly applied chemoattractant stimuli. Classical patch clamp methodology is applied to allow for controlled shielding of a membrane patch by measuring the seal resistivity. In Dictyostelium cells, a seal resistivity of 50 MOmega proved to be tight enough to exclude molecules from diffusing into the shielded membrane region. This allowed for separating a shielded and a non shielded region of a cell membrane to study the spatiotemporal dynamics of intracellular chemotactic signaling events at the interface between shielded and non-shielded areas. The spatiotemporal dynamics of signaling events in the membrane was read out by means of appropriate fluorescent markers using laser scanning confocal microscopy. PMID- 27271911 TI - Quantitative Monitoring Spatiotemporal Activation of Ras and PKD1 Using Confocal Fluorescent Microscopy. AB - Receptor activation upon ligand binding induces activation of multiple signaling pathways. To fully understand how these signaling pathways coordinate, it is essential to determine the dynamic nature of the spatiotemporal activation profile of signaling components at the level of single living cells. Here, we outline a detailed methodology for visualizing and quantitatively measuring the spatiotemporal activation of Ras and PKD1 by applying advanced fluorescence imaging techniques, including multichannel, simultaneous imaging and Forster resonance energy transfer (FRET). PMID- 27271913 TI - Use of Resonance Energy Transfer Techniques for In Vivo Detection of Chemokine Receptor Oligomerization. AB - Since the first reports on chemokine function, much information has been generated on the implications of these molecules in numerous physiological and pathological processes, as well as on the signaling events activated through their binding to receptors. As is the case for other G protein-coupled receptors, chemokine receptors are not isolated entities that are activated following ligand binding; rather, they are found as dimers and/or higher order oligomers at the cell surface, even in the absence of ligands. These complexes form platforms that can be modified by receptor expression and ligand levels, indicating that they are dynamic structures. The analysis of the conformations adopted by these receptors at the membrane and their dynamics is thus crucial for a complete understanding of the function of the chemokines. We focus here on the methodology insights of new techniques, such as those based on resonance energy transfer for the analysis of chemokine receptor conformations in living cells. PMID- 27271914 TI - Multi-State Transition Kinetics of Intracellular Signaling Molecules by Single Molecule Imaging Analysis. AB - The chemotactic signaling of eukaryotic cells is based on a chain of interactions between signaling molecules diffusing on the cell membrane and those shuttling between the membrane and cytoplasm. In this chapter, we describe methods to quantify lateral diffusion and reaction kinetics on the cell membrane. By the direct visualization and statistic analyses of molecular Brownian movement achieved by single-molecule imaging techniques, multiple states of membrane-bound molecules are successfully revealed with state transition kinetics. Using PTEN, a phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) 3'-phosphatase, in Dictyostelium discoideum undergoing chemotaxis as a model, each process of the analysis is described in detail. The identified multiple state kinetics provides an essential clue to elucidating the molecular mechanism of chemoattractant induced dynamic redistribution of the signaling molecule asymmetrically on the cell membrane. Quantitative parameters for molecular reactions and diffusion complement a conventional view of the chemotactic signaling system, where changing a static network of molecules connected by causal relationships into a spatiotemporally dynamic one permits a mathematical description of stochastic migration of the cell along a shallow chemoattractant gradient. PMID- 27271915 TI - Mathematics of Experimentally Generated Chemoattractant Gradients. AB - Many eukaryotic cells move in the direction of a chemical gradient. Several assays have been developed to measure this chemotactic response, but no complete mathematical models of the spatial and temporal gradients are available to describe the fundamental principles of chemotaxis. Here we provide analytical solutions for the gradients formed by release of chemoattractant from a point source by passive diffusion or forced flow (micropipettes) and gradients formed by laminar diffusion in a Zigmond chamber. The results show that gradients delivered with a micropipette are formed nearly instantaneously, are very steep close to the pipette, and have a steepness that is strongly dependent on the distance from the pipette. In contrast, gradients in a Zigmond chamber are formed more slowly, are nearly independent of the distance from the source, and resemble the temporal and spatial properties of the natural cAMP wave that Dictyostelium cells experience during cell aggregation. PMID- 27271916 TI - Modeling Excitable Dynamics of Chemotactic Networks. AB - The study of chemotaxis has benefited greatly from computational models that describe the response of cells to chemoattractant stimuli. These models must keep track of spatially and temporally varying distributions of numerous intracellular species. Moreover, recent evidence suggests that these are not deterministic interactions, but also include the effect of stochastic variations that trigger an excitable network. In this chapter we illustrate how to create simulations of excitable networks using the Virtual Cell modeling environment. PMID- 27271917 TI - Sky-Blue Organic Light Emitting Diode with 37% External Quantum Efficiency Using Thermally Activated Delayed Fluorescence from Spiroacridine-Triazine Hybrid. AB - Extremely efficient sky-blue organic electroluminescence with external quantum efficiency of ~37% is achieved in a conventional planar device structure, using a highly efficient thermally activated delayed fluorescence emitter based on the spiroacridine-triazine hybrid and simultaneously possessing nearly unitary (100%) photoluminescence quantum yield, excellent thermal stability, and strongly horizontally oriented emitting dipoles (with a horizontal dipole ratio of 83%). PMID- 27271918 TI - Constipation is casting a shadow over everyday life - a systematic review on older people's experience of living with constipation. AB - AIMS AND OBJECTIVES: To explore and summarise best evidence of how constipation affects the daily living of older people from their own perspective. Furthermore, to assess how interventions aimed at treating constipation in older people affect patient-reported outcome such as quality of life. BACKGROUND: Constipation is a common and overlooked problem with an impact on everyday life, especially among older people. Older people seem to have individual preconceptions on constipation which can influence the strategies used to prevent and treat constipation. DESIGN: A systematic review, integrating findings from both qualitative and quantitative studies. METHOD: Systematic searches were carried out in PubMed, CINAHL, PsycINFO and EMBASE on the 31st of July 2014. A search strategy was constructed with key concepts identified using PICO to identify quantitative studies and PIC(o) to identify qualitative studies. Search terms included constipation, elderly, aged, elderly people, aged people, quality of life, patient experience, patient perspective, meaning, emotion, psychological. Reference lists were searched manually. RESULTS: A total of nine studies were included in the review, five quantitative and four qualitative. Three main themes crystallised from the results of the included studies: bodily experiences, everyday life shadowed by constipation and adverse psychological effects. CONCLUSION: Constipation among older people was connected to subjective and comprehensive experiences. It had a negative impact on physical and mental well being as well as the social life of older people. The review also showed that older people had individual and personal strategies, based on their own beliefs. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals need to be aware of the experiences of living with constipation as well as the range of strategies used by patients to prevent and treat constipation. The patient perspective on constipation needs to be integrated in the strategies and actions carried out by healthcare professionals. PMID- 27271919 TI - Systematic unenhanced CT for acute abdominal symptoms in the elderly patients improves both emergency department diagnosis and prompt clinical management. AB - OBJECTIVES: To assess the added-value of systematic unenhanced abdominal computed tomography (CT) on emergency department (ED) diagnosis and management accuracy compared to current practice, in elderly patients with non-traumatic acute abdominal symptoms. METHODS: Institutional review board approval and informed consent were obtained. This prospective study included 401 consecutive patients 75 years of age or older, admitted to the ED with acute abdominal symptoms, and investigated by early systematic unenhanced abdominal CT scan. ED diagnosis and intended management before CT, after unenhanced CT, and after contrast CT if requested, were recorded. Diagnosis and management accuracies were evaluated and compared before CT (clinical strategy) and for two conditional strategies (current practice and systematic unenhanced CT). An expert clinical panel assigned a final diagnosis and management after a 3-month follow-up. RESULTS: Systematic unenhanced CT significantly improved the accurate diagnosis (76.8% to 85%, p=1.1x10-6) and management (88.5% to 95.8%, p=2.6x10-6) rates compared to current practice. It allowed diagnosing 30.3% of acute unsuspected pathologies, 3.4% of which were unexpected surgical procedure requirement. CONCLUSIONS: Systematic unenhanced abdominal CT improves ED diagnosis accuracy and appropriate management in elderly patients presenting with acute abdominal symptoms compared to current practice. KEY POINTS: * Systematic unenhanced CT improves significantly diagnosis accuracy compared to current practice. * Systematic unenhanced CT optimizes appropriate hospitalization by increasing the number of discharged patients. * Systematic unenhanced CT allows detection of about one third of acute unsuspected abdominal conditions. * It should allow boosting emergency department management decision-making confidence in old patients. PMID- 27271920 TI - Usefulness of colour Doppler flow imaging in the management of lacrimal gland lesions. AB - OBJECTIVE: To assess the role of colour Doppler flow imaging (CDFI) in the diagnosis and management of lacrimal fossa lesions. METHODS: Institutional ethical committee approval was obtained. Fifty-one patients with 62 lacrimal fossa lesions were retrospectively included from 2003-2015. All patients underwent conventional ultrasonography and CDFI, with a qualitative and quantitative analysis of the vascularization. All patients had lacrimal gland surgery. Definitive diagnosis was based on pathological examination. RESULTS: The study included 47 non-epithelial lesions (NEL) and 15 epithelial lesions (EL), with 24 (39 %) malignant lesions and 38 (61 %) benign lesions. NEL were significantly more likely to present with septa (p < 0.001), hypoechogenicity (p < 0.001), high vascular intensity (p < 0.001), both central and peripheral vascularization (p < 0.001), tree-shape vascularization (p < 0.05) and a low resistance index (RI) (p < 0.0001). EL were significantly more likely to present with the presence of cysts (p < 0.001), and a higher RI. Receiver operating characteristic curves identified a RI value of 0.72 as the best cut-off to differentiate NEL from EL, with a sensitivity and specificity of 100 %. CONCLUSION: CDFI is a valuable tool in the differential diagnosis of lacrimal fossa lesions. Resistance index measurement enables substantial distinction between EL and NEL, thus providing crucial data for surgical management. KEY POINTS: * CDFI is a valuable tool in lacrimal fossa lesions. * Resistance Index measurement enables substantial distinction between epithelial and non-epithelial lesions. * Management of patients becomes more appropriate. PMID- 27271921 TI - Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders. AB - OBJECTIVES: Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS detected lactate as a marker of mitochondrial disease. METHODS: Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, >=1 major criteria), 'probable' (n = 10, >=2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. RESULTS: MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. CONCLUSION: MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. KEY POINTS: * MRS-detected brain tissue lactate levels can be quantified. * MRS lactate and lactate/Cr are increased in children with mitochondrial disease. * CSF lactate is less suitable as marker of mitochondrial disease. PMID- 27271922 TI - Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial. AB - OBJECTIVES: To demonstrate non-inferiority of iobitridol 350 for coronary CT angiography (CTA) compared to higher iodine content contrast media regarding rate of patients evaluable for the presence of coronary artery stenoses. METHODS: In this multicentre trial, 452 patients were randomized to receive iobitridol 350, iopromide 370 or iomeprol 400 and underwent coronary CTA using CT systems with 64 detector rows or more. Two core lab readers assessed 18 coronary segments per patient regarding image quality (score 0 = non diagnostic to 4 = excellent quality), vascular attenuation, signal and contrast to noise ratio (SNR, CNR). Patients were considered evaluable if no segment had a score of 0. RESULTS: Per patient, the rate of fully evaluable CT scans was 92.1, 95.4 and 94.6 % for iobitridol, iopromide and iomeprol, respectively. Non-inferiority of iobitridol over the best comparator was demonstrated with a 95 % CI of the difference of [ 8.8 to 2.1], with a pre-specified non-inferiority margin of -10 %. Although average attenuation increased with higher iodine concentrations, average SNR and CNR did not differ between groups. CONCLUSIONS: With current CT technology, iobitridol 350 mg iodine/ml is not inferior to contrast media with higher iodine concentrations in terms of image quality for coronary stenosis assessment. KEY POINTS: * Iodine concentration is an important parameter for image quality in coronary CTA. * Contrast enhancement must be balanced against the amount of iodine injected. * Iobitridol 350 is non-inferior compared to CM with higher iodine concentrations. * Higher attenuation with higher iodine concentrations, but no SNR or CNR differences. PMID- 27271924 TI - Decreased stage migration rate of early gastric cancer with a new reconstruction algorithm using dual-energy CT images: a preliminary study. AB - OBJECTIVES: To evaluate the potential value of advanced monoenergetic images (AMEIs) on early gastric cancer (EGC) using dual-energy CT (DECT). METHODS: 31 EGC patients (19 men, 12 women; age range, 38-81 years; mean age, 57.19 years) were retrospectively enrolled in this study. Conventionally reconstructed polyenergetic images (PEIs) at 120 kV and virtual monoenergetic images (MEIs) and AMEIs at six different kiloelectron volt (keV) levels (from 40 to 90 keV) were evaluated from the 100 and Sn 140 kV dual energy image data, respectively. The visibility and stage migration of EGC for all three image data sets were evaluated and statistically analyzed. The objective and subjective image qualities were also evaluated. RESULTS: AMEIs at 40 keV showed the best visibility (80.7 %) and the lowest stage migration (35.5 %) for EGC. The stage migration for AMEIs at 40 keV was significantly lower than that for PEIs (p = 0.026). AMEIs at 40 keV had statistically higher CNR in the arterial and portal phases, gastric-specific diagnostic performance and visual sharpness compared with other AMEIs, MEIs and PEIs (all p < 0.05). CONCLUSIONS: AMEIs at 40 keV with MPR increase the CNR of EGC and thus potentially lower the stage migration of EGC. KEY POINTS: * AMEIs benefits from the recombination of low-keV images and medium energies. * AMEIs could receive better CNR results than MEIs. * AMEIs at 40 keV potentially lower the stage migration of EGC. PMID- 27271923 TI - Diffusion-weighted magnetic resonance imaging predicts survival in patients with liver-predominant metastatic colorectal cancer shortly after selective internal radiation therapy. AB - OBJECTIVES: To investigate whether quantifications of apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) can predict overall survival (OS) in patients with liver-predominant metastatic colorectal cancer (CRC) following selective internal radiation therapy with 90Yttrium-microspheres (SIRT). METHODS: Forty-four patients underwent DWI 19 +/- 16 days before and 36 +/- 10 days after SIRT. Tumour-size and intratumoral minimal ADC (minADC) values were measured for 132 liver metastases on baseline and follow-up DWI. Optimal functional imaging response to treatment was determined by receiver operating characteristics and defined as >=22 % increase in post-therapeutic minADC. Survival analysis was performed with the Kaplan-Meier method and Cox-regression comparing various variables with potential impact on OS. RESULTS: Median OS was 8 months. The following parameters were significantly associated with median OS: optimal functional imaging response (18 vs. 5 months; p < 0.001), hepatic tumour burden <50 % (8 vs. 5 months; p = 0.018), Eastern Cooperative Oncology Group performance scale <1 (10 vs. 4 months; p = 0.012) and progressive disease according to Response and Evaluation Criteria in Solid Tumours (8 vs. 3 months; p = 0.001). On multivariate analysis, optimal functional imaging response and hepatic tumour burden remained independent predictors of OS. CONCLUSION: Functional imaging response assessment using minADC changes on DWI may predict survival in CRC shortly after SIRT. KEY POINTS: * Relative minADC changes may predict survival in liver-predominant metastatic colorectal cancer following SIRT * Intratumoral minADC changes by >=22 % were best to predict an improved overall survival * Functional imaging response assessment is feasible before anatomic tumour-size changes occur * minADC changes might guide future therapy management in sequential lobar radioembolization approaches. PMID- 27271926 TI - Imaging the heart failure patient-need for accurate measurements of left ventricular volumes and ejection fraction: the role of three-dimensional and contrast echocardiography. AB - PURPOSE OF REVIEW: Left ventricular ejection fraction (LVEF) is a powerful prognostic marker in heart failure and plays a pivotal role in the allocation of many treatments that reduce morbidity and mortality. Although unenhanced two dimensional echocardiography (2DE) is the most ubiquitous tool for the assessment of left ventricular (LV) size and systolic function, it does not provide reliable, reproducible and accurate measures. The purpose of this review is to critically appraise contrast echocardiography and three-dimensional echocardiography (3DE) for the assessment of LVEF and LV volumes. RECENT FINDINGS: Contrast echocardiography results in more accurate assessment of LVEF and LV volumes than unenhanced 2DE, significantly improving correlation with cardiac magnetic resonance, with comparable reproducibility. Contrast echocardiography reduces downstream testing, frequently alters patient management, and results in substantial cost savings. 3DE shows higher levels of agreement with cardiac magnetic resonance over unenhanced 2DE for LVEF and LV volumes, but requires adequate image quality, and consistently underestimates LV volumes due to limited spatial resolution. SUMMARY: The advent of contrast 2DE and 3DE has marked the dawn of significant improvements in the precision and reproducibility of echocardiography. Contrast 3DE improves LV assessment in patients with suboptimal images, but further work is needed to demonstrate incremental benefit over contrast echocardiography. PMID- 27271925 TI - Feasibility of self-gated isotropic radial late-phase MR imaging of the liver. AB - OBJECTIVE: To evaluate feasibility of a 3D-isotropic self-gated radial volumetric interpolated breath-hold examination (VIBE) for late-phase MRI of the liver. MATERIAL AND METHODS: 70 patients were included and underwent liver MRI at 1.5 T. Depending on the diagnosis, either Gd-EOB-DTPA (35 patients) or gadobutrol (35 patients) were administered. During late (gadobutrol) or hepatocyte-specific phase (Gd-EOB-DTPA), a radial prototype sequence was acquired and reconstructed using (1) self-gating with 40 % acceptance (rVIBE40); (2) with 100 % acceptance of the data (rVIBE100) and compared to Cartesian VIBE (cVIBE). Images were assessed qualitatively (image quality, lesion conspicuity, artefacts; 5-point Likert-scale: 5 = excellent; two independent readers) and quantitatively (coefficient-of-variation (CV); contrast-ratio) in axial and coronal reformations. RESULTS: In eight cases only rVIBE provided diagnostic image quality. Image quality of rVIBE40 was rated significantly superior (p < 0.05) in Gd-EOB-DTPA-enhanced and coronal reformatted examinations as compared to cVIBE. Lesion conspicuity was significantly improved (p < 0.05) in coronal reformatted Gd-EOB-DTPA-enhanced rVIBE40 in comparison to cVIBE. CV was higher in rVIBE40 as compared to rVIBE100/cVIBE (p < 0.01). Gadobutrol-enhanced rVIBE40 and cVIBE showed higher contrast-ratios than rVIBE100 (p < 0.001), whereas no differences were found in Gd-EOB-DTPA-enhanced examinations. CONCLUSION: Self-gated 3D isotropic rVIBE provides significantly superior image quality compared to cVIBE, especially in multiplanar reformatted and Gd-EOB-DTPA-enhanced examinations. KEY POINTS: * Radial VIBE acquisition reduces motion artefacts. * Gd-EOB-DTPA enhanced scans provide improved image quality. * Non-diagnostic liver MRI examinations may be reduced by radial k-spaces sampling. PMID- 27271927 TI - Aberrant Methylation of FOXE1 Contributes to a Poor Prognosis for Patients with Colorectal Cancer. AB - BACKGROUND: Hypermethylation of DNA silences gene expression and is an important event in colorectal cancer (CRC). This study aimed to identify aberrantly methylated genes that contribute to a poor prognosis for patients with CRC. METHODS: The study comprehensively explored DNA methylation microarray profiles from 396 CRC samples and 45 normal control samples in a database and selected aberrantly methylated transcription factors associated with prognosis and metastasis. Using quantitative reverse transcription polymerase chain reaction, the identified genes in 140 patients with CRC were validated to assess the relationship between expression of methylated genes and prognosis. RESULTS: In the study, FOXE1 was newly identified as a gene associated with prognosis and metastasis in CRC. Expression of FOXE1 in CRC tissues was significantly lower than in normal colorectal tissues (p = 0.01). The survival rate for the patients with low expression of FOXE1 was significantly lower than that for patients with high expression of FOXE1 in uni- and multivariate analyses. Inhibition of DNA methylation recovered FOXE1 expression in CRC cells. CONCLUSIONS: Methylation mediated silencing of FOXE1 expression was shown to be a potential prognostic factor in CRC. PMID- 27271928 TI - Laparoscopic Right Hepatectomy for Cirrhotic Patients: Takasaki's Hilar Control and Caudal Approach. AB - BACKGROUND: Cirrhotic patients bearing hepatocellular carcinomas (HCC) derive benefits from laparoscopic hepatectomy1 - 6 such as reduced bleeding, less overall and liver-specific complications, and fewer adhesions in the case of future reoperation or transplantation.7 - 10 Bleeding is concerning in the setting of cirrhosis,11 - 15 and adequate inflow control reduces blood loss. The caudal approach is the laparoscopic counterpart of the anterior approach to open surgery. It implies in parenchymal transection initiated from the visceral surface of the liver after limited hepatic mobilization, reducing the risk of increased circulating tumoral cells.16 - 18 Venous outflow transection and completion of ligament mobilization are left as last steps. METHODS: A 46 years old-male with hepatitis C virus and alcoholic cirrhosis was diagnosed with a 4-cm HCC (right hepatic lobe). Expected future liver remnant was 45 % of his total liver volume. A totally laparoscopic right hepatectomy was performed using six ports, and the specimen was removed through a Pfannenstiel auxiliary incision. A 10-mm 30 degrees scope was used. The pneumoperitoneum pressure was set to 12 mmHg. The right hepatic pedicle, the caudate lobe, and the major hepatic veins were managed with laparoscopic vascular staplers. RESULTS: Surgery was performed with limited liver mobilization and en bloc extrafascial right pedicle control (Takasaki's technique),19 followed by caudal parenchymal transection along the paracaval plane. The operative time was 450 min, and the estimated blood loss was 800 ml (no transfusion was required). CONCLUSION: The laparoscopic Takasaki technique and caudal approach are feasible procedures in the setting of cirrhosis, resulting in an oncologic adequate intervention with less morbidity. PMID- 27271929 TI - It's Freezing to Death. PMID- 27271930 TI - Can We Predict the Lateral Compartment Lymph Node Involvement in RET-Negative Patients with Medullary Thyroid Carcinoma? AB - BACKGROUND: Lateral lymph node dissection (LND) in the absence of macroscopic nodal metastasis remains controversial in sporadic medullary thyroid carcinoma (MTC). OBJECTIVES: The aims of our study were to determine the risk of lateral lymph node (LN) metastases with a focus on lateral contralateral N1, and to define a risk-adapted surgical treatment for these patients. METHODS: All patients who underwent surgery from 1980 to 2012 for previously untreated RET negative MTC were reviewed. We focused on the lateral compartments of LN metastases and identified three groups: no lateral LN metastases, ipsilateral lateral (ILL)-LN metastases with no contralateral LN involvement, and contralateral lateral (CLL)-LN metastases. RESULTS: Overall, 131 patients underwent surgery for RET-negative MTC. A total thyroidectomy with LND was performed in 112 patients (85 %), including 97 patients who had an ILL-LND and 92 patients who had a CLL-LND. Lateral LN metastases (N1) occurred in 40 patients (37 %): 31 patients (32 %) had ILL-LN metastases with no contralateral LN involvement, and 9 patients (10 %) had CLL-LN metastases. The preoperative cut offs for LN metastases in the ILL compartment were very low, with a smallest tumor size of 5 mm, and lowest serum calcitonin level of 38 pg/ml. Disease-free survival rates decreased from 92 % for patients with no lateral LN metastases to 41 % for patients with ILL-LN metastases and 0 % for patients with CLL-LN metastases. CONCLUSIONS: ILL-LND should be performed in every patient and only a minority of MTC patients with small micro-MTC, and low serum calcitonin levels should not have a CLL-LND. PMID- 27271931 TI - Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis. AB - Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-beta, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS. PMID- 27271933 TI - Video Modeling and Observational Learning to Teach Gaming Access to Students with ASD. AB - The purpose of this study was to evaluate both video modeling and observational learning to teach age-appropriate recreation and leisure skills (i.e., accessing video games) to students with autism spectrum disorder. Effects of video modeling were evaluated via a multiple probe design across participants and criteria for mastery were based on these results. Secondary measures were collected on observational learning across participants and behaviors. Participants included 4 children with autism, ages 8-11, who were served in self-contained special education classrooms. Results indicated a functional relation between video modeling and increased independence in gaming; observational learning occurred for at least some steps across students. Results, implications for practitioners, limitations, and ideas for future research are discussed. PMID- 27271932 TI - Validation of the Movie for the Assessment of Social Cognition in Adolescents with ASD: Fixation Duration and Pupil Dilation as Predictors of Performance. AB - Impaired social cognition is one of the core characteristics of autism spectrum disorders (ASD). Appropriate measures of social cognition for high-functioning adolescents with ASD are, however, lacking. The Movie for the Assessment of Social Cognition (MASC) uses dynamic social stimuli, ensuring ecological validity, and has proven to be a sensitive measure in adulthood. In the current study, 33 adolescents with ASD and 23 controls were administered the MASC, while concurrent eye tracking was used to relate gaze behavior to performance levels. The ASD group exhibited reduced MASC scores, with social cognition performance being explained by shorter fixation duration on eyes and decreased pupil dilation. These potential diagnostic markers are discussed as indicators of different processing of social information in ASD. PMID- 27271934 TI - Interventional left atrial appendage occlusion: added value of 3D transesophageal echocardiography for device sizing. AB - Aim of this study was the assessment of left atrial appendage (LAA) dimensions comparing 2D- to 3D-TEE measurements in patients with nonvalvular atrial fibrillation undergoing percutaneous LAA occlusion. Patients underwent transesophageal echocardiography (TEE) before, during and 45 days after intervention. The maximal LAA orifice diameters in 2D-TEE (LODmax 2D) were obtained from multiple views. Test-retest reliability (screening vs. implantation), inter- and intra-observer variability for echocardiographic parameters were assessed by two independent examiners. Overall, 74 patients underwent percutaneous LAA occlusion. 2D-TEE significantly underestimated the maximal LAA orifice diameter compared with 3D-TEE (screening LODmax 2D 21.11 +/- 2.75 mm vs. 22.52 +/- 3.45 mm for LODmax 3D, p < 0.001; during implantation LODmax 2D 21.56 +/- 3.48 mm vs. 22.99 +/- 3.24 mm for LODmax 3D, p < 0.001). The intraobserver and interobserver variability calculated as coefficient of variation (CV) were both lower for the 3D-TEE quantification of the maximal orifice diameter (intraobserver CV for 3D-TEE 6.07 % vs. 9.31 % for 2D-TEE; interobserver CV for 3D-TEE 6.73 % vs. 9.69 % for 2D-TEE). Compared to 3D-TEE the test-retest reliability of 2D-TEE showed a lower intraclass correlation coefficient calculated as average of raters (0.92 for 3D-TEE vs. for 2D-TEE 0.78). Firstly, 2D-TEE significantly underestimates the maximal LAA orifice diameter compared to 3D-TEE. Secondly, 3D-TEE measurements are associated with a lower observer variability and higher reliability than 2D-TEE. PMID- 27271935 TI - Pericardial inflammation with reversible constriction: prediction of recovery with cardiovascular magnetic resonance. PMID- 27271937 TI - Electricity, water, and natural gas consumption of a residential house in Canada from 2012 to 2014. AB - With the cost of consuming resources increasing (both economically and ecologically), homeowners need to find ways to curb consumption. The Almanac of Minutely Power dataset Version 2 (AMPds2) has been released to help computational sustainability researchers, power and energy engineers, building scientists and technologists, utility companies, and eco-feedback researchers test their models, systems, algorithms, or prototypes on real house data. In the vast majority of cases, real-world datasets lead to more accurate models and algorithms. AMPds2 is the first dataset to capture all three main types of consumption (electricity, water, and natural gas) over a long period of time (2 years) and provide 11 measurement characteristics for electricity. No other such datasets from Canada exist. Each meter has 730 days of captured data. We also include environmental and utility billing data for cost analysis. AMPds2 data has been pre-cleaned to provide for consistent and comparable accuracy results amongst different researchers and machine learning algorithms. PMID- 27271936 TI - Aluminium Diphosphamethanides: Hidden Frustrated Lewis Pairs. AB - The synthesis and characterisation of two aluminium diphosphamethanide complexes, [Al(tBu)2 {kappa(2) P,P'-Mes*PCHPMes*}] (3) and [Al(C6 F5 )2 {kappa(2) P,P' Mes*PCHPMes*}] (4), and the silylated analogue, Mes*PCHP(SiMe3 )Mes* (5), are reported. The aluminium complexes feature four-membered PCPAl core structures consisting of diphosphaallyl ligands. The silylated phosphine 5 was found to be a valuable precursor for the synthesis of 4 as it cleanly reacts with the diaryl aluminium chloride [(C6 F5 )2 AlCl]2 . The aluminium complex 3 reacts with molecular dihydrogen at room temperature under formation of the acyclic sigma(2) lambda(3) ,sigma(3) lambda(3) -diphosphine Mes*PCHP(H)Mes* and the corresponding dialkyl aluminium hydride [tBu2 AlH]3 . Thus, 3 belongs to the family of so called hidden frustrated Lewis pairs. PMID- 27271938 TI - Effective ingredients of verbal de-escalation: validating an English modified version of the 'De-Escalating Aggressive Behaviour Scale'. AB - WHAT IS KNOWN ON THE SUBJECT?: Verbal de-escalation is an intervention aimed at calmly managing an agitated client to prevent violence. Effective de-escalation can help reduce the use of seclusion and restraint in psychiatric settings. Despite its importance in practice, there is little agreement on the necessary techniques of de-escalation and most of the research on the topic is based on expert opinion. To our knowledge, only one attempt at quantifying de-escalation skill has been pursued through the German-language De-Escalating Aggressive Behaviour Scale (DABS). While the DABS identified seven qualities necessary for de-escalation, it has not been validated in English and may lack important descriptors. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The present study enhanced the original DABS with best, acceptable and least desirable staff de escalation practice descriptions for each of the seven items. This enhancement of the DABS lead to the creation of the English modified DABS (EMDABS). The EMDABS was psychometrically validated for use in research and practice: raters could use the EMDABS with a high level of agreement and consistency. Also, the scale appeared to measure a single cohesive construct - de-escalation. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: With further validation, the EMDABS has potential to be the first English quantitative measure of de-escalation. The EMDABS offers seven items, with associated best practice descriptions, that may be used to inform de-escalation practice. The EMDABS can be used to evaluate training and education programmes and inform how these programmes and independent de escalation practice may be improved. ABSTRACT: Introduction Verbal de-escalation is crucial to a non-coercive psychiatric environment. Despite its importance, the literature on de-escalation is sparse and mostly qualitative. To address this, Nau et al. (2009) quantified de-escalation by creating the German-language De Escalating Aggressive Behaviour Scale (DABS). The DABS provides seven skills necessary for de-escalation, however it has not been validated in English and lacks the necessary anchor descriptions to make it useful. Aim To modify the DABS to include descriptions of best, acceptable and least desirable staff practice and to validate the English modified DABS (EMDABS). Method To develop item descriptions for the EMDABS, 50 conflictual staff-patient interactions were reviewed, summarized and cross-referenced with the literature (n = 19). Three raters then used the EMDABS to evaluate 272 simulations depicting these interactions. Results The EMDABS demonstrated very good inter-rater reliability [ICC (3, 1) = 0.752] and strong internal consistency (alpha = 0.901). A factor analysis revealed that the seven items were best represented by a single factor. Discussion The EMDABS was validated for future use in research and practice. Additional validation and future research directions are discussed. Implications for practice The EMDABS holds promise as a quantitative measure of de-escalation. Its seven items and best practice guidelines have clinical implications for improving practice and training. PMID- 27271939 TI - Accurate Automatic Detection of Densely Distributed Cell Nuclei in 3D Space. AB - To measure the activity of neurons using whole-brain activity imaging, precise detection of each neuron or its nucleus is required. In the head region of the nematode C. elegans, the neuronal cell bodies are distributed densely in three dimensional (3D) space. However, no existing computational methods of image analysis can separate them with sufficient accuracy. Here we propose a highly accurate segmentation method based on the curvatures of the iso-intensity surfaces. To obtain accurate positions of nuclei, we also developed a new procedure for least squares fitting with a Gaussian mixture model. Combining these methods enables accurate detection of densely distributed cell nuclei in a 3D space. The proposed method was implemented as a graphical user interface program that allows visualization and correction of the results of automatic detection. Additionally, the proposed method was applied to time-lapse 3D calcium imaging data, and most of the nuclei in the images were successfully tracked and measured. PMID- 27271941 TI - Application of ultrasound-guided percutaneous intrahepatic portal vein catheterization with antibiotic injection for treating unliquefied bacterial liver abscess. AB - AIM: To investigate whether ultrasound-guided percutaneous portal vein catheterization can be successfully carried out in the intrahepatic region of patients with unliquefied bacterial liver abscess (UBLA), who are subsequently treated with an injection of antibiotics. METHODS: Thirty-two UBLA patients were enrolled in this study. Among them, 13 patients were included in the experimental group; an ultrasound-guided percutaneous portal vein catheterization was undertaken in the intrahepatic region of these patients, and they also received an injection of antibiotics. The remaining 19 patients were retrospectively included in the control group; these patients only received systemic antibiotic therapy. The efficacy of intervention was compared with that of systemic treatment. RESULTS: The catheterization procedures were successful in all the patients of the experimental group. However, two cases (15.4%) developed complications postoperatively. Compared to the control group, the following parameters of the experimental group were significantly shorter/lower: (i) duration for regaining normal body temperature; (ii) time period for achieving normal white blood cell count; (iii) length of hospitalization; (iv) cases of liquefied liver abscess during follow-up; and (v) cost of hospitalization (P < 0.05). CONCLUSION: Ultrasound-guided percutaneous portal vein catheterization is a simple, minimally invasive, and effective treatment for UBLA. It must be carried out in the intrahepatic region and a subsequent injection of antibiotics must be given. PMID- 27271940 TI - Event-related potentials and cognitive performance in multiple sclerosis patients with fatigue. AB - The aim of this study was to evaluate event-related potentials (ERP) and cognition in multiple sclerosis (MS) patients with regard to fatigue and disease related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS/MFISmod). N200 and P300 components of auditory ERP were analyzed. Cognition was evaluated by means of Brief Repeatable Battery of Neuropsychological Tests (BRBNT). The results of ERP and BRBNT were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P300 latency was significantly longer in the whole MS group and in the fatigued patients than in the controls. A positive correlation was found between P300 latency and MFIS/MFISmod results, independent from age and MS-related variables. The fatigued patients scored less than non-fatigued ones in tests evaluating memory, visuomotor abilities and attention. Results of these tests correlated significantly with fatigue measures, independently from MS-related variables. Fatigue in MS patients showed significant relationships with impairment within the memory and attention domains. Parameters of auditory ERP, as electrophysiological biomarkers of cognitive performance, were not independently linked to fatigue. PMID- 27271943 TI - Nitrogen-Mediated Interaction: A Walnut-Aphid-Parasitoid System. AB - The effects of plant quality on natural enemies are often overlooked in planning and executing biological control programs for insect pests in agriculture. Plant quality, however, could help to explain some of the observed variation in effectiveness of biological control, as it can indirectly influence natural enemy populations. In this study, we used the walnut aphid Chromaphis juglandicola (Kaltenbach) to address the effect of increased nitrogen availability to the host plant on parasitism by the specialist parasitoid Trioxys pallidus (Haliday). In laboratory experiments with walnut seedlings, a higher chlorophyll content index of the foliage in response to added nitrogen was correlated with a decrease in the number of mummies produced by female parasitoids over a 24-h period but an increase in the proportion and the size of female offspring. In field sampling of walnut orchards, there was no relationship between the percent parasitism of walnut aphids by T. pallidus and the chlorophyll content index of the trees. Nitrogen fertilizer and plant quality can clearly affect biological control and should be given greater consideration in integrated pest management. PMID- 27271942 TI - Proteomic analysis of stress-related proteins and metabolic pathways in Picea asperata somatic embryos during partial desiccation. AB - Partial desiccation treatment (PDT) stimulates germination and enhances the conversion of conifer somatic embryos. To better understand the mechanisms underlying the responses of somatic embryos to PDT, we used proteomic and physiological analyses to investigate these responses during PDT in Picea asperata. Comparative proteomic analysis revealed that, during PDT, stress related proteins were mainly involved in osmosis, endogenous hormones, antioxidative proteins, molecular chaperones and defence-related proteins. Compared with those in cotyledonary embryos before PDT, these stress-related proteins remained at high levels on days 7 (D7) and 14 (D14) of PDT. The proteins that differentially accumulated in the somatic embryos on D7 were mapped to stress and/or stimuli. They may also be involved in the glyoxylate cycle and the chitin metabolic process. The most significant difference in the differentially accumulated proteins occurred in the metabolic pathways of photosynthesis on D14. Furthermore, in accordance with the changes in stress-related proteins, analyses of changes in water content, abscisic acid, indoleacetic acid and H2 O2 levels in the embryos indicated that PDT is involved in water-deficit tolerance and affects endogenous hormones. Our results provide insight into the mechanisms responsible for the transition from morphologically mature to physiologically mature somatic embryos during the PDT process in P. asperata. PMID- 27271944 TI - Gut Content Analysis of a Phloem-Feeding Insect, Bactericera cockerelli (Hemiptera: Triozidae). AB - Potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), is a key pest of potato (Solanum tuberosum L., Solanales: Solanaceae) and a vector of "Candidatus Liberibacter solanacearum," the pathogen associated with zebra chip disease. In addition to its presence on cultivated crops, the psyllid regularly occurs on numerous uncultivated annual and perennial species within the Solanaceae. A better understanding of landscape-level ecology of B. cockerelli would substantially improve our ability to predict which potato fields are most likely to be colonized by infected psyllids. We developed three PCR-based methods of gut content analysis to identify what plant species B. cockerelli had previously fed upon. These methods included-1) sequencing PCR amplicons of regions of plant-derived internal transcribed spacer (ITS) or the chloroplast trnL gene from psyllids, 2) high-resolution melting analysis of ITS or trnL real time PCR products, and 3) restriction enzyme digestion of trnL PCR product. Each method was used to test whether we could identify psyllids that had been reared continuously on potato versus psyllids reared continuously on the perennial nightshade, Solanum dulcamara. All three methods of gut content analysis correctly identified psyllids from potato and psyllids from S. dulcamara Our study is the first to demonstrate that plant DNA can be detected in a phloem feeding insect. Gut content analysis, in combination with other landscape ecology approaches, could help elucidate patterns in landscape-level movements and host plant associations of B. cockerelli. PMID- 27271945 TI - Prey and Pollen Food Choice Depends on Previous Diet in an Omnivorous Predatory Mite. AB - The time allocated by omnivorous predators to consuming prey versus plant provided foods (e.g., pollen) directly influences their efficacy as biocontrol agents of agricultural pests. Nonetheless, diet shifting between these two very different food sources remains poorly understood. We hypothesized that previous diet composition influences subsequent choice of prey and plant food types. We tested this hypothesis by observing the foraging choices of Amblyseius swirskii (Athias-Henriot) mites (Mesostigmata: Phytoseiidae), which were first maintained on either prey (broad mites) or corn pollen, and then offered familiar and unfamiliar foods. A. swirskii exhibited strong fidelity to familiar food, whether prey or pollen, suggesting there are physiological or behavioral costs involved in shifting between such different foods. Results illustrate the importance of previous diet for subsequent pest consumption by omnivorous natural enemies. PMID- 27271946 TI - Seasonal Population Dynamics of Three Potato Pests in Washington State. AB - Pest phenology models allow producers to anticipate pest outbreaks and deploy integrated pest management (IPM) strategies. Phenology models are particularly useful for cropping systems with multiple economically damaging pests throughout a season. Potato (Solanum tuberosum L.) crops of Washington State, USA, are attacked by many insect pests including the potato tuberworm (Phthorimaea operculella Zeller), the beet leafhopper (Circulifer tenellus Baker), and the green peach aphid (Myzus persicae Sulzer). Each of these pests directly damages potato foliage or tubers; C. tenellus and M. persicae also transmit pathogens that can drastically reduce potato yields. We monitored the seasonal population dynamics of these pests by conducting weekly sampling on a network of commercial farms from 2007 to 2014. Using these data, we developed phenology models to characterize the seasonal population dynamics of each pest based on accumulated degree-days (DD). All three pests exhibited consistent population dynamics across seasons that were mediated by temperature. Of the three pests, C. tenellus was generally the first detected in potato crops, with 90% of adults captured by 936 DD. In contrast, populations of P. operculella and M. persicae built up more slowly over the course of the season, with 90% cumulative catch by 1,590 and 2,634 DD, respectively. Understanding these seasonal patterns could help potato producers plan their IPM strategies while allowing them to move away from calendar-based applications of insecticides. More broadly, our results show how long-term monitoring studies that explore dynamics of multiple pest species can aid in developing IPM strategies in crop systems. PMID- 27271947 TI - Habitat Preference of German Mantis religiosa Populations (Mantodea: Mantidae) and Implications for Conservation. AB - In Germany, the thermophilic European mantid (Mantis religiosa L.) is endangered. Here, we study habitat requirements during its life, and discuss the applicability of the two conservation measures grazing and mowing to this insect species. At two study sites in south-western Germany, which were each subject to one of these measures, we recorded structural and climatic conditions within different microhabitats. We also conducted capture-mark-recapture studies for adult M. religiosa, and mapped adult roosting, oothecae deposition, egg hatching, and imaginal molting in microhabitats over two vegetation periods. In order to assess microhabitat preference of M. religiosa during its life, and identify climatic conditions driving preferences, we applied the Lille habitat preference index and conducted logistic regression analysis for life phases. Our results suggest that temperature is important for egg and nymph development. For egg deposition, females preferred solid substrates with high heat-storing capacities, as those attenuate the negative influence of cold weather periods on egg development. Being ambush predators, males and females preferred roosting sites with sufficient shelter and high prey abundance. Contrary to our expectation, the conservation measures reduced adult population sizes, and presumably reproduction rates. We thus suggest that mowing during the adult phase should reduce vegetation height to a moderate level to keep prey abundance high. Mowing with a clearing saw or grazing over a short period in small fenced areas should be preferred over prolonged grazing, as grazers collaterally stamp down the vegetation. Grazers indirectly reduce prey availability by deteriorating prevailing microclimatic conditions. PMID- 27271948 TI - The Effects of Crop Intensification on the Diversity of Native Pollinator Communities. AB - Increases in agricultural conversion are leading to declines in native grasslands and natural resources critical for beneficial insects. However, little is known regarding how these changes affect pollinator diversity. Land use types were categorized within 300 m and 3 km radii of pollinator sampling locations in Brookings County, SD. Pollinator abundance and species richness were regressed on the proportion of the landscape dedicated to row crops, grass and pasture, forage crops, small grains, and aquatic habitats using variance components modeling. Row crops had a negative effect on bee abundance at 300 m, after fixed effects modeling accounted for outliers skewing this relationship. At 3 km, corn positively affected bee abundance and richness, while soybean acreage decreased species richness. The landscape matrix of outlying sites consisted of large monocultured areas with few alternative habitat types available, leading to inflated populations of Melissodes and Halictidae. Syrphids had a positive parabolic relationship between diversity and row crops, indicating potential for competitive exclusion from intermediate landscapes. Unlike other studies, landscape diversity within 300 m was not found to significantly benefit pollinator diversity. Within especially agriculturally developed areas of the region, high abundances of pollinators suggest selection for a few dominant species. There was no effect of forage crops or aquatic habitats on pollinator diversity, indicating that less highly managed areas still represent degraded habitat within the landscape. Incorporating pollinator-friendly crops at the farm level throughout the region is likely to enhance pollinator diversity by lessening the negative effects of large monocultures. PMID- 27271949 TI - The Influence of Exotic Lady Beetle (Coleoptera: Coccinellidae) Establishment on the Species Composition of the Native Lady Beetle Community in Missouri. AB - The diversity and abundance of native lady beetles (Coccinellidae) in North America has declined in recent decades. This decline is often correlated with the introduction and establishment of exotic lady beetle species, including Coccinella septempunctata L. and Harmonia axyridis Pallas, suggesting that exotic species precipitated the decline of native lady beetles. We examined species records of native coccinellids in Missouri over 118 yr and asked whether the species composition of the community experienced a shift following the establishment of the exotic species. We found that the contemporary native coccinellid community is different from the community that was present nearly a century ago. However, there was no evidence for a recent abrupt shift in composition triggered by the establishment of exotic species. Instead, our data suggest that the native lady beetle community has been undergoing consistent and gradual change over time, with some species decreasing in abundance and others increasing. While not excluding exotic species as a factor contributing to the decline of native lady beetle species, our findings suggest that other continuous factors, like land use change, may have played a more influential role in determining the composition of the native coccinellid communities within our region. PMID- 27271950 TI - Generalist Behavior Describes Pollen Foraging for Perceived Oligolectic and Polylectic Bees. AB - Native bees provide essential pollination services to cultivated and wild plants worldwide. Despite the need to conserve pollinators, the foraging patterns of native bees are poorly understood. Classic concepts of resource use have typically categorized bee species as specialists or generalists based on floral visitation patterns. While intraspecific variation in bee foraging likely depends on local land use, sex, and phenological period, among other factors, these potential drivers of floral visitation are rarely explicitly investigated. In this study, we explore the potential for inter- and intra-specific variation in floral visitation by investigating the pollen loads of two solitary, similarly sized, ground-nesting native bee species within the Apinae, Melissodes tepaneca (Cresson) and Diadasia rinconis (Cockerell), categorized as generalist and specialist based on past floral visitation studies, respectively. Our analyses reveal generalist foraging and indicate that natural habitat availability significantly drives pollen load composition for both species. The putative specialist, D. rinconis, exhibited significant differences in pollen load composition between males and females, between pan and net collection methods, and between the different phenological periods. The putative generalist, M. tepaneca, exhibited significant differences in pollen load composition between the sexes, but only in the late season. Both species exhibited significant preference levels for multiple native plant species across the study region. Given that pollen collection is essential for native bee population persistence across natural and human-dominated habitats, our findings suggest consideration of both pollen collection and floral visitation patterns to holistically describe floral usage and develop pollinator conservation strategies. PMID- 27271951 TI - Association of Autoimmune Encephalitis With Combined Immune Checkpoint Inhibitor Treatment for Metastatic Cancer. AB - IMPORTANCE: Paraneoplastic encephalitides usually precede a diagnosis of cancer and are often refractory to immunosuppressive therapy. Conversely, autoimmune encephalitides are reversible conditions that can occur in the presence or absence of cancer. OBJECTIVE: To report the induction of autoimmune encephalitis in 2 patients after treatment of metastatic cancer with a combination of the immune checkpoint inhibitors nivolumab and ipilimumab. DESIGN, SETTING, AND PARTICIPANTS: A retrospective case study was conducted of the clinical and management course of 2 patients with progressive, treatment-refractory metastatic cancer who were treated with a single dose each (concomitantly) of the immune checkpoint inhibitors nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg. EXPOSURES: Nivolumab and ipilimumab. MAIN OUTCOMES AND MEASURES: The clinical response to immunosuppressive therapy in suspected autoimmune encephalitis in the setting of immune checkpoint inhibitor use. RESULTS: Autoantibody testing confirmed identification of anti-N-methyl-D-aspartate receptor antibodies in the cerebrospinal fluid of 1 patient. Withdrawal of immune checkpoint inhibitors and initiation of immunosuppressive therapy, consisting of intravenous methylprednisolone sodium succinate equivalent to 1000 mg of methylprednisolone for 5 days, 0.4 mg/kg/d of intravenous immunoglobulin for 5 days, and 2 doses of rituximab, 1000 mg, in 1 patient and oral prednisone, 60 mg/d, in the other patient, resulted in improved neurologic symptoms. CONCLUSIONS AND RELEVANCE: Immune checkpoint inhibition may favor the development of immune responses against neuronal antigens, leading to autoimmune encephalitis. Early recognition and treatment of autoimmune encephalitis in patients receiving immune checkpoint blockade therapy will likely be essential for maximizing clinical recovery and minimizing the effect of drug-related toxic effects. The mechanisms by which immune checkpoint inhibition may contribute to autoimmune encephalitis require further study. PMID- 27271952 TI - Investigation of Thermal Effects of Photocoagulation on Retinal Tissue Using Fine Motion-Sensitive Dynamic Optical Coherence Tomography. AB - To enable an objective evaluation of photocoagulation, we characterize thermal tissue changes induced by laser irradiation with different laser parameters using optical coherence tomography (OCT). Spectral-domain OCT with a newly developed image processing method was used to monitor the thermal changes of ex vivo porcine retina. A sequence of OCT B-scans was obtained at the same retinal position simultaneously with the photocoagulation. Cross-sectional tissue displacement maps with respect to an OCT image taken before laser irradiation were computed for images taken before, during, and after laser irradiation, by using a correlation-based custom algorithm. Cross-sectional correlation maps (OCT correlation maps) were also computed from an OCT image taken before laser irradiation as a base-line to visualize alterations of tissue microstructure induced by laser irradiation. By systematically controlling laser power and exposure times, tissue displacements and structural changes of 200 retinal regions of 10 porcine eyes were characterized. Thermal tissue changes were characterized by B-scan images, OCT correlation maps, and tissue displacement maps. Larger tissue deformation was induced with higher laser power and shorter exposure time, while the same total laser energy (10 mJ) was applied. The measured tissue displacements revealed the complicated dynamics of tissue displacements. Three types of dynamics were observed; lateral expansion, lateral constriction, and a type showing more complicated dynamics. The results demonstrated the ability of this OCT-based method to evaluate retinal changes induced by laser irradiation. This evaluation could lead to further understanding of thermal effects, and increasing reproducibility of photocoagulation therapy. PMID- 27271953 TI - The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single-centre study. AB - OBJECTIVE: The syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency. DESIGN: Prospective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium <= 130 mmol/l) between January 1st and October 1st 2015. PATIENTS: A total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43.4%) initially classified as SIAD. MAIN OUTCOME MEASURES: (i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency. RESULTS: Central nervous system diseases were the commonest cause of SIAD (n = 148, 26%) followed by pulmonary diseases (n = 111, 19%), malignancy (n = 105, 18%) and drugs (n = 47, 8%). A total of 22 patients (3.8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration. CONCLUSIONS: In a large, prospective and well-defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co-occurred in 3.8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1.5% of cases presenting as euvolaemic hyponatraemia. PMID- 27271954 TI - Ethnic Disparities in Blood Pressure: A Population-based Study. AB - Taiwan's indigenous population exhibits a higher mortality of cardiovascular disease, but current research has not reported any associations among ethnicities on the blood pressure (BP). We randomly selected representative samples in this population-based study. We measured height, weight, hip and waist circumferences, and blood pressure in a screening survey. Systolic BP and diastolic BP were significantly higher in the indigenous population. Among women, prevalence rates of DBP > 90 mmHg among indigenes (32.9 %) were significantly high than those in Han Chinese (17.4 %). Based on multivariate analysis adjusted for covariates, the results showed gender and ethnicity to be significantly correlated with systolic and diastolic BP. Gender was a modifier between ethnicity and BP. Furthermore, we found an additive effect between ethnicity and age on systolic and diastolic BP by gender. Our study showed independent additive effects on systolic BP and diastolic BP between ethnicity and age by gender. PMID- 27271955 TI - Indigenous Adolescents' Suicidal Behaviors and Risk Factors: Evidence from the National Youth Risk Behavior Survey. AB - The study sought to examine indigenous adolescents' suicidal behaviors and risk factors in a nationally representative sample and explore potential causes of disparities. The study analyzed the 1991-2013 Youth Risk Behavior Survey National Combined Datasets. Suicidal behavior outcomes included suicide consideration, planning, and attempts during the past 12 months. Logit regressions were used to estimate the effects of potential suicide risk factors on these suicidal behaviors. The results showed that a high percentage of indigenous adolescents exhibited suicidal behaviors (consideration: 24.6 %; planning: 20.7 %; attempts: 16.2 %). After adjusting for risk factors, indigenous adolescents were no more likely than other adolescents to consider or plan for suicide (consideration: OR 1.18, CI 0.96-1.45, p = 0.125; planning: OR 1.16, CI 0.95-1.42, p = 0.156); however, they remained significantly more likely to have made suicide attempts (OR 1.73, CI 1.32-2.26, p < 0.001). Disparities in adolescent suicidal behaviors could be explained by the heterogeneous prevalence of suicidal risk factors across different races/ethnicities. PMID- 27271956 TI - Distribution of IL28B Polymorphism in a Cohort of Italians and Immigrants with HCV Infection: Association with Viraemia, Stage of Fibrosis and Response to Treatment. AB - Aims of the study are to investigate, in a cohort of patients affected by HCV chronic hepatitis with genotypes 1 and 4, the prevalence of interleukin 28B (IL28B) genotypes, the possible association between IL28B polymorphism and severity of liver damage, the role of IL28B CC as a predictor of outcome. 365 patients with HCV infection were observed between 2013 and 2014. Demographic, virological, biochemical, and genetic characteristics of each patient were investigated. Liver fibrosis was assessed by transient elastometry. Mean age of the patients (72.9 % males, 27.1 % females) is 50 years. 91.5 % % of patients are Caucasian, 8.5 % African. In the patients with HCV1 and HCV4 a higher frequency of IL28B CT is observed with a prevalence of 52.1 and 61.8 % respectively. As regards ethnic group, African people have a prevalence of 35.5 % for CC, while Caucasians have a prevalence of 23.8 % for CC. In our cohort, IL28B polymorphism does not show significant differences among ethnic groups and in HCV1 and HCV4 genotypes. As described in literature, IL28B CC genotype is confirmed as predictor of sustained virological response in both Caucasians and Africans. A significant correlation between liver fibrosis and IL28B polymorphism emerges. PMID- 27271957 TI - Wavelength-selective orbital angular momentum generation based on a plasmonic metasurface. AB - Nanoapertures with space-variant geometries are designed in a gold thin film to construct an ultrathin plasmonic metasurface, which has been demonstrated both numerically and experimentally to selectively generate and focus orbital angular momentum (OAM) beams with different topological charges at the wavelengths of 930 nm and 766 nm, respectively. Moreover, the interference patterns between the different circularly polarized transmission light were used to confirm the topological charges unambiguously. The agreement between the simulated and measured results suggests that the metasurface of wavelength-selective OAM modes may have potential applications in future optical communication systems. PMID- 27271959 TI - The 6-Item Cognitive Impairment Test as a bedside screening for dementia in general hospital patients: results of the General Hospital Study (GHoSt). AB - OBJECTIVE: The objective of this study was to examine the psychometric quality of the 6-Item Cognitive Impairment Test (6CIT) as a bedside screening for the detection of dementia in general hospital patients. METHOD: Participants (N = 1,440) were inpatients aged >=65 of 33 randomly selected general hospitals in Southern Germany. The 6CIT was conducted at bedside, and dementia was diagnosed according to DSM-IV. Nursing staff was asked to rate the patients' cognitive status, and previous diagnoses of dementia were extracted from medical records. Completion rates and validity statistics were calculated. RESULTS: Two-hundred seventy patients had dementia. Cases with delirium but no dementia were excluded. Feasibility was 97.9% and 83.3% for patients without and with dementia, respectively, and decreased from moderate (93.8%) to severe dementia (53%). The area under the curve of the 6CIT was 0.98. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for the cutoffs 7/8 (0.96, 0.82, 0.85, 0.52, 0.99) and 10/11 (0.88, 0.95, 0.94, 0.76, 0.98). The nurse ratings and medical records information had lower validity statistics. Logistic regression analyses revealed that the 6CIT statistically significantly provided information above nurse ratings and medical records. Twenty-five and 37 additional patients were correctly classified by the 7/8 and 10/11 cutoffs, respectively. CONCLUSION: The 6CIT is a feasible and valid screening tool for the detection of dementia in older general hospital patients. The 6CIT outperformed the nurse ratings of cognitive status and dementia diagnoses from medical records, suggesting that standardized screening may have benefits with regard to case finding. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27271958 TI - Quantification methods for human and large animal leukocytes using DNA dyes by flow cytometry. AB - Ovine and bovine blood is used heavily within the development of blood-handling medical devices, such as heart pumps (left ventricular assist devices, LVADs), for which blood cell damage needs to be monitored during in vitro testing. Hematology analyzers provide cell counts but no information about cell viability. The anthraquinone DNA dyes CyTRAK OrangeTM and DRAQ7TM have practical and spectral properties rendering them suitable for multicolor assays. Compared to other DNA dyes such as Vybrant Dyecycle, CyTRAK Orange enables a faster staining protocol and does not require incubation at +37 degrees C. Compared to traditional viability dyes such as propidium iodide and 7AAD, DRAQ7's unique spectral profile of excitation in both blue and red lasers and far-red emission enables identification of dual positive dead cell events and frees up detectors for use with other reagents. CyTRAK Orange and DRAQ7 could be used in combination with absolute counting bead standards to provide cell counts and viability but the combination of these dyes has previously only been used for microscopy on rodent cells. The purpose of this study was to evaluate the use of these dyes in combination in large animal blood samples for flow cytometry. A viability and cell counting protocol for bovine, ovine, and human leukocytes using CyTRAK Orange and DRAQ7 was prepared. Four different counting bead standards were evaluated using the Navios and FACSAria cytometers and compared to counts obtained from hematology analyzers. CyTRAK Orange successfully detected CD45(+) leukocytes in all species. The DRAQ7 single-stained dead cell counts correlated well with the CyTRAK Orange/DRAQ7 double-stained dead cell counts in human and bovine blood, but not in ovine blood, which could be related to the blood source. In conclusion, for human and bovine blood, this method works well for viability counts using different flow cytometers and bead standards. (c) 2016 International Society for Advancement of Cytometry. PMID- 27271960 TI - Booster dose vaccination for preventing hepatitis B. AB - BACKGROUND: Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection. OBJECTIVES: To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016). SELECTION CRITERIA: Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin. DATA COLLECTION AND ANALYSIS: Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants with anamnestic immune response in non-protected participants and signs of HBV infection. Secondary outcomes were the proportion of participants that developed local and systemic adverse events following a booster dose injection. We planned to report the weighted proportion with 95% confidence intervals (CIs). MAIN RESULTS: There were no eligible randomised clinical trials fulfilling the inclusion criteria of this review. AUTHORS' CONCLUSIONS: We were unable to include any randomised clinical trials on the topic; only randomised clinical trials will be able to provide an answer as to whether a booster dose vaccination is able to protect against hepatitis B infection. PMID- 27271961 TI - Atrophy of the tongue following complete versus partial hypoglossal nerve transection in a canine model. AB - OBJECTIVES/HYPOTHESIS: The hypoglossal nerve (XII) has been used as a donor nerve in facial and laryngeal reinnervation. The purpose of this study was to investigate the neuromuscular changes that occur within the tongue following partial or complete transection of XII using a canine model. STUDY DESIGN: Histopathological comparison of tongue denervation following two types of XII resection in a canine model. METHODS: Ten adult canines underwent complete unilateral resection of XII or resection of only the medial terminal branch of the hypoglossal nerve (mXII). After 6 months of recovery, tongue specimens were analyzed histopathologically using whole cross-sections. Routine histologic sections were assessed by two neuropathologists blinded to the type of denervation. The cross-sectional area was calculated of both sides of the tongue, and the amount of myosin was quantified morphometrically using immunohistochemistry for myosin (antimyosin heavy chain, fast isotype). Statistical comparison between partial and complete denervation was performed using the Student t test. RESULTS: Six months following XII transection, quantitative measures of the cross-sectional area of the tongue and content of myosin demonstrated severe muscle atrophy on the operated side of the tongue for both groups, compared to the nonoperated side. For partial transection involving only mXII, the degree of atrophy was less severe (P < .05). CONCLUSIONS: This study provides new histological information demonstrating that partial resection of the hypoglossal nerve, sacrificing only the proximal medial branch of the hypoglossal nerve (mXII), results in less severe atrophy of the tongue than complete transection of the entire hypoglossal nerve. LEVEL OF EVIDENCE: NA Laryngoscope, 126:2689-2693, 2016. PMID- 27271962 TI - Complexity and Specificity of the Neutrophil Transcriptomes in Juvenile Idiopathic Arthritis. AB - NIH projects such as ENCODE and Roadmap Epigenomics have revealed surprising complexity in the transcriptomes of mammalian cells. In this study, we explored transcriptional complexity in human neutrophils, cells generally regarded as nonspecific in their functions and responses. We studied distinct human disease phenotypes and found that, at the gene, gene isoform, and miRNA level, neutrophils exhibit considerable specificity in their transcriptomes. Thus, even cells whose responses are considered non-specific show tailoring of their transcriptional repertoire toward specific physiologic or pathologic contexts. We also found that miRNAs had a global impact on neutrophil transcriptome and are associated with innate immunity in juvenile idiopathic arthritis (JIA). These findings have important implications for our understanding of the link between genes, non-coding transcripts and disease phenotypes. PMID- 27271963 TI - Coherent commensurate electronic states at the interface between misoriented graphene layers. AB - Graphene and layered materials in general exhibit rich physics and application potential owing to their exceptional electronic properties, which arise from the intricate pi-orbital coupling and the symmetry breaking in twisted bilayer systems. Here, we report room-temperature experiments to study electrical transport across a bilayer graphene interface with a well-defined rotation angle between the layers that is controllable in situ. This twisted interface is artificially created in mesoscopic pillars made of highly oriented pyrolytic graphite by mechanical actuation. The overall measured angular dependence of the conductivity is consistent with a phonon-assisted transport mechanism that preserves the electron momentum of conduction electrons passing the interface. The most intriguing observations are sharp conductivity peaks at interlayer rotation angles of 21.8 degrees and 38.2 degrees . These angles correspond to a commensurate crystalline superstructure leading to a coherent two-dimensional (2D) electronic interface state. Such states, predicted by theory, form the basis for a new class of 2D weakly coupled bilayer systems with hitherto unexplored properties and applications. PMID- 27271964 TI - High-speed atomic force microscopy shows that annexin V stabilizes membranes on the second timescale. AB - Annexins are abundant cytoplasmic proteins that can bind to negatively charged phospholipids in a Ca(2+)-dependent manner, and are known to play a role in the storage of Ca(2+) and membrane healing. Little is known, however, about the dynamic processes of protein-Ca(2+)-membrane assembly and disassembly. Here we show that high-speed atomic force microscopy (HS-AFM) can be used to repeatedly induce and disrupt annexin assemblies and study their structure, dynamics and interactions. Our HS-AFM set-up is adapted for such biological applications through the integration of a pumping system for buffer exchange and a pulsed laser system for uncaging caged compounds. We find that biochemically identical annexins (annexin V) display different effective Ca(2+) and membrane affinities depending on the assembly location, providing a wide Ca(2+) buffering regime while maintaining membrane stabilization. We also show that annexin is membrane recruited and forms stable supramolecular assemblies within ~5 s in conditions that are comparable to a membrane lesion in a cell. Molecular dynamics simulations provide atomic detail of the role played by Ca(2+) in the reversible binding of annexin to the membrane surface. PMID- 27271965 TI - Spatial metrology of dopants in silicon with exact lattice site precision. AB - Scaling of Si-based nanoelectronics has reached the regime where device function is affected not only by the presence of individual dopants, but also by their positions in the crystal. Determination of the precise dopant location is an unsolved problem in applications from channel doping in ultrascaled transistors to quantum information processing. Here, we establish a metrology combining low temperature scanning tunnelling microscopy (STM) imaging and a comprehensive quantum treatment of the dopant-STM system to pinpoint the exact coordinates of the dopant in the Si crystal. The technique is underpinned by the observation that STM images contain atomic-sized features in ordered patterns that are highly sensitive to the STM tip orbital and the absolute dopant lattice site. The demonstrated ability to determine the locations of P and As dopants to 5 nm depths will provide critical information for the design and optimization of nanoscale devices for classical and quantum computing applications. PMID- 27271966 TI - Transmission of Hand, Foot and Mouth Disease and Its Potential Driving Factors in Hong Kong. AB - Hand-foot-and-mouth disease (HFMD) is a common childhood disease with substantial disease burden in Asia. Mixed results were reported on the associations between HFMD incidence and meteorological factors or school holidays, while limited studies focused on their association on transmissibility. We aimed to measure the transmissibility of HFMD and to examine its potential driving factors in Hong Kong. A likelihood-based procedure was used to estimate time-dependent effective reproduction number (Rt) based on weekly number of HFMD-associated hospitalizations from 2010 to 2014. The associations of between-year effects, depletion of susceptibles, absolute humidity and school holidays with Rt were examined using linear regression. Rt usually started increasing between early spring and summer and peaked in April to May at around 1.1-1.2, followed by a slight rebound in autumn. Depletion of susceptibles and between-years effects explained most of the variances (19 and 13% respectively) in Rt. We found a negative association between depletion of susceptibles and Rt (coefficients ranged from -0.14 to -0.03 for different years), but the estimated effects of absolute humidity and school holidays were insignificant. Overall, HFMD transmission was moderate in Hong Kong and was mainly associated with depletion of susceptibles. Limited impact was suggested from meteorological factors and school holidays. PMID- 27271967 TI - Long-Term Prophylactic Antibiotic Treatment: Effects on Survival, Immunocompetence and Reproduction Success of Parasemia plantaginis (Lepidoptera: Erebidae). AB - Hundreds of insect species are nowadays reared under laboratory conditions. Rearing of insects always implicates the risk of diseases, among which microbial infections are the most frequent and difficult problems. Although there are effective prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths' survival and life-history traits during the following 10 mo, and compared them to those of untreated control larvae. Prophylactic antibiotic treatment had no effect on survival but we show effects on some life-history traits by decreasing the developmental time of treated larvae. However, we also revealed relevant negative effects, as antibiotic treated individuals show a decreased number of laid eggs and also furthermore a suppressed immunocompetence. These results implicate, that a prophylactic medication can also lead to negative effects on life-history traits and reproductive success, which should be seriously taken in consideration when applying a prophylactic treatment to laboratory reared insect populations. PMID- 27271968 TI - Non-Nutritive Polyol Sweeteners Differ in Insecticidal Activity When Ingested by Adult Drosophila melanogaster (Diptera: Drosophilidae). AB - Previous work showed the non-nutritive polyol sweetener Erythritol was toxic when ingested by Drosophila melanogaster (Meigen, 1930). This study assessed whether insect toxicity is a general property of polyols. Among tested compounds, toxicity was highest for erythritol. Adult fruit flies (D. melanogaster) fed erythritol had reduced longevity relative to controls. Other polyols did not reduce longevity; the only exception was a weaker but significant reduction of female (but not male) longevity when flies were fed D-mannitol. We conclude at least some non-nutritive polyols are not toxic to adult D. melanogaster when ingested for 17 days. The longer time course (relative to erythritol) and female specificity of D-mannitol mortality suggests different mechanisms for D-mannitol and erythritol toxicity to D. melanogaster. PMID- 27271969 TI - Spatio-Temporal Distribution of Bark and Ambrosia Beetles in a Brazilian Tropical Dry Forest. AB - Bark and the ambrosia beetles dig into host plants and live most of their lives in concealed tunnels. We assessed beetle community dynamics in tropical dry forest sites in early, intermediate, and late successional stages, evaluating the influence of resource availability and seasonal variations in guild structure. We collected a total of 763 beetles from 23 species, including 14 bark beetle species, and 9 ambrosia beetle species. Local richness of bark and ambrosia beetles was estimated at 31 species. Bark and ambrosia composition was similar over the successional stages gradient, and beta diversity among sites was primarily determined by species turnover, mainly in the bark beetle community. Bark beetle richness and abundance were higher at intermediate stages; availability of wood was the main spatial mechanism. Climate factors were effectively non-seasonal. Ambrosia beetles were not influenced by successional stages, however the increase in wood resulted in increased abundance. We found higher richness at the end of the dry and wet seasons, and abundance increased with air moisture and decreased with higher temperatures and greater rainfall. In summary, bark beetle species accumulation was higher at sites with better wood production, while the needs of fungi (host and air moisture), resulted in a favorable conditions for species accumulation of ambrosia. The overall biological pattern among guilds differed from tropical rain forests, showing patterns similar to dry forest areas. PMID- 27271970 TI - Molecular Characterization of Two Fatty Acyl-CoA Reductase Genes From Phenacoccus solenopsis (Hemiptera: Pseudococcidae). AB - Fatty acyl-CoA reductases (FARs) are key enzymes involved in fatty alcohol synthesis. Here, we cloned and characterized full-length cDNAs of two FAR genes from the cotton mealybug, Phenacoccus solenopsis. The results showed PsFAR I and PsFAR II cDNAs were 1,584 bp and 1,515 bp in length respectively. Both PsFAR I and PsFAR II were predicted to be located in the endoplasmic reticulum by Euk mPLoc 2.0 approach. Both of them had a Rossmann folding region and a FAR_C region. Two conservative motifs were discovered in Rossmann folding region by sequence alignment including a NADPH combining motif, TGXXGG, and an active site motif, YXXXK. A phylogenetic tree made using MEGA 6.06 indicated that PsFAR I and PsFAR II were placed in two different branches. Gene expression analysis performed at different developmental stages showed that the expression of PsFar I is significantly higher than that of PsFar II in first and second instar nymphs and in male adults. Spirotetramat treatment at 125 mg/liter significantly increased the expression of PsFar I in third instar nymphs, but there was no effect in the expression of PsFar II Our results indicated these two FAR genes showed different expression patterns during insect development and after pesticide treatment, suggesting they play different roles in insect development and detoxification against pesticides. PMID- 27271971 TI - Selection of Valid Reference Genes for Reverse Transcription Quantitative PCR Analysis in Heliconius numata (Lepidoptera: Nymphalidae). AB - Identifying the genetic basis of adaptive variation is challenging in non-model organisms and quantitative real time PCR. is a useful tool for validating predictions regarding the expression of candidate genes. However, comparing expression levels in different conditions requires rigorous experimental design and statistical analyses. Here, we focused on the neotropical passion-vine butterflies Heliconius, non-model species studied in evolutionary biology for their adaptive variation in wing color patterns involved in mimicry and in the signaling of their toxicity to predators. We aimed at selecting stable reference genes to be used for normalization of gene expression data in RT-qPCR analyses from developing wing discs according to the minimal guidelines described in Minimum Information for publication of Quantitative Real-Time PCR Experiments (MIQE). To design internal RT-qPCR controls, we studied the stability of expression of nine candidate reference genes (actin, annexin, eF1alpha, FK506BP, PolyABP, PolyUBQ, RpL3, RPS3A, and tubulin) at two developmental stages (prepupal and pupal) using three widely used programs (GeNorm, NormFinder and BestKeeper). Results showed that, despite differences in statistical methods, genes RpL3, eF1alpha, polyABP, and annexin were stably expressed in wing discs in late larval and pupal stages of Heliconius numata This combination of genes may be used as a reference for a reliable study of differential expression in wings for instance for genes involved in important phenotypic variation, such as wing color pattern variation. Through this example, we provide general useful technical recommendations as well as relevant statistical strategies for evolutionary biologists aiming to identify candidate-genes involved adaptive variation in non model organisms. PMID- 27271972 TI - Western Pacific hydroclimate linked to global climate variability over the past two millennia. AB - Interdecadal modes of tropical Pacific ocean-atmosphere circulation have a strong influence on global temperature, yet the extent to which these phenomena influence global climate on multicentury timescales is still poorly known. Here we present a 2,000-year, multiproxy reconstruction of western Pacific hydroclimate from two speleothem records for southeastern Indonesia. The composite record shows pronounced shifts in monsoon rainfall that are antiphased with precipitation records for East Asia and the central-eastern equatorial Pacific. These meridional and zonal patterns are best explained by a poleward expansion of the Australasian Intertropical Convergence Zone and weakening of the Pacific Walker circulation (PWC) between ~1000 and 1500 CE Conversely, an equatorward contraction of the Intertropical Convergence Zone and strengthened PWC occurred between ~1500 and 1900 CE. Our findings, together with climate model simulations, highlight the likelihood that century-scale variations in tropical Pacific climate modes can significantly modulate radiatively forced shifts in global temperature. PMID- 27271973 TI - Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality. AB - BACKGROUND: Previous studies suggest that lymphovascular invasion (LVI) has a weak and variable effect on prognosis. It is uncertain whether LVI, determined by diagnostic prostate biopsy, predicts prostate cancer death. Data from experimental studies have indicated that carcinoma-associated fibroblasts in the reactive stroma could promote LVI and progression to metastasis. Thus, combining LVI with reactive stromal grade may identify prostate cancer patients at high risk of an unfavorable outcome. The purpose of the present study was to examine if LVI, determined by diagnostic biopsy, alone and in combination with reactive stromal grade could predict prostate cancer death. METHODS: This population-based study included 283 patients with prostate cancer diagnosed by needle biopsy in Aust-Agder County (Norway) from 1991 to 1999. Clinical data were obtained by medical charts review. Two uropathologists evaluated LVI and reactive stromal grade. The endpoint was prostate cancer death. RESULTS: Patients with LVI had marginally higher risk of prostate cancer death compared to patients without LVI (hazard ratio: 1.8, P-value = 0.04). LVI had a stronger effect on prostate cancer death risk when a high reactive stromal grade was present (hazard ratio: 16.0, P value <0.001). Therefore, patients with concomitant LVI and high reactive stromal grade were at particularly high risk for prostate cancer death. CONCLUSIONS: Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27271975 TI - Author's reply to 'Rickettsia retinitis cases in India: a few comments'. AB - Diagnosis of rickettsial retinitis remains presumptive when gold standard tests are not available or not done due to financial constrains. History of tick bite followed by fever with skin rash particularly in winter and spring season may point towards Rickettsiosis. The absence of scarring post resolution of rickettsial retinitis suggests inner retinal involvement in contrast to toxoplasmosis. Bilaterality of the disease, 2-4 weeks of latent period, and multifocal nature of retinitis lesions (cotton wool spot-like lesions) especially around the disc and posterior pole may suggest an immune response to recent systemic infection. The use of only antibiotics or only steroids or both together for treatment of rickettsial retinitis is controversial and warrants randomized controlled trials. PMID- 27271974 TI - Fluorescent Mechanism-Based Probe for Aerobic Flavin-Dependent Enzyme Activity. AB - Diversity in non-ribosomal peptide and polyketide secondary metabolism is facilitated by interactions between biosynthetic domains with discrete monomer loading and their cognate tailoring enzymes, such as oxidation or halogenation enzymes. The cooperation between peptidyl carrier proteins and flavin-dependent enzymes offers a specialized strategy for monomer selectivity for oxidization of small molecules from within a complex cellular milieu. In an effort to study this process, we have developed fluorescent probes to selectively label aerobic flavin dependent enzymes. Here we report the preparation and implementation of these tools to label oxidase, monooxygenase, and halogenase flavin-dependent enzymes. PMID- 27271976 TI - How could analyzing the activity of two matrix metalloproteinases unveil the cause of sudden cardiac death. AB - Sudden cardiac death is natural, unexpected death, related to cardiovascular disease. Its postmortem elucidation is significant, as the family of the deceased aspires to prevent other sudden deaths. Irrespective of the proper etiological entity, the myocardial collagen matrix remodels, associated with the progression of cardiovascular diseases. It has become evident that many mediators such as humoral factors, transforming growth factor (TGF)-beta1 among them, are involved in the remodeling process. Cardiac remodeling is the balance of regenerative and eliminatory processes that include enzymes involved in the degradation of extracellular matrix (ECM) components. Enzymes capable of degrading native fibrillar collagen are interstitial collagenases, specifically matrix metalloproteinases (MMP)-1 and MMP-8. Here, we suggest a technique of visualizing turnover of collagen in cardiac tissue. PMID- 27271978 TI - First International Conference on Risk Perception, Communication and Ethics of Exposures to Ionizing Radiation (RICOMET)-special section editorial. PMID- 27271977 TI - Neuroprotective effect of grape seed extract against cadmium toxicity in male albino rats. AB - Cadmium toxicity can disturb brain chemistry leading to depression, anxiety, and weakened immunity. Cadmium disturbs the neurotransmitter dopamine, resulting in low energy, lack of motivation, and depression, which are predisposing factors for violence. The purpose of this study was to evaluate the ameliorative effect of grape seed extract (GSE) on the brain of 40 male albino rats after exposure to cadmium chloride (Cd) toxicity. The rats were separated into either the control group, the Cd group, the GSE group, or the GSE and Cd mixture (treated) group. The cerebrum showed evidence of degeneration of some nerve fibers and cells. Fibrosis, vacuolations, and congestion in the blood vessels were demonstrated. Satelletosis was located in the capsular cells. Immunohistochemical expression of Bax was strongly positive in the Cd group and decreased in the treated group. These histopathological changes were decreased in the brain tissue of the treated group, but a few blood vessels still had evidence of congestion. Cadmium administration increased the level of MDA and decreased MAO-A, acetylcholinesterase, and glutathione reductase (GR), while the treatment with GSE affected the alterations in these parameters. In addition, cadmium downregulated the mRNA expression levels of GST and GPx, while GSE treatment normalized the transcript levels. The expression of both dopamine and 5 hydroxytryptamine transporter was downregulated in the rats administered cadmium and the addition of GSE normalized the expression of these aggression associated genes. PMID- 27271979 TI - Pattern of invasion and lymphovascular invasion in squamous cell carcinoma of the floor of the mouth: an interobserver variability study. AB - AIMS: Lymphovascular invasion (LVI) and the histological pattern of invasion (POI) at the invasive tumour front have been reported as adverse prognosticators in oral squamous cell carcinoma (SCC). However, assessment of these parameters is hampered by variation in the criteria used for their evaluation. Our objective was to evaluate interobserver variability in the assessment of the POI and LVI in SCC of the floor of the mouth (FOM), and to study the impact of the POI on clinical outcomes by using varying quantitative cut-offs. METHODS AND RESULTS: Fifty-eight cases of FOM SCC were independently evaluated for the POI and LVI by three pathologists. Interobserver variability was analysed by the use of Fleiss kappa statistics. Interobserver agreement was substantial for the assessment of LVI [kappa = 0.64, 95% confidence interval (CI) 0.60-0.68]. Interobserver agreement was moderate for evaluation of the POI with a 50% cut-off (kappa = 0.58, 95% CI 0.54-0.62), a 20% cut-off (kappa = 0.58, 95% CI 0.54-0.62) cut-off, and worst POI (kappa =0 .43, 95% CI 0.39-0.46). A consensus diagnosis of the POI was a significant predictor of locoregional recurrence (LRR), disease-specific survival (DSS) and overall survival (OS) on univariate analysis when a 50% cut off was used (LRR, P = 0.01; DSS, P = 0.01; OS, P = 0.01) and when a 20% cut-off was used (LRR, P = 0.02; DSS, P = 0.02; OS, P = 0.03), but was not significant when worst POI was used (LRR, P = 0.18; DSS, P = 0.16; OS, P = 0.17). CONCLUSIONS: Interobserver agreement in the diagnosis of LVI was substantial. The POI at the 50% and 20% cut-offs is moderately reproducible, and has prognostic value in FOM SCC. Further studies are necessary to establish the optimum quantitative cut-off for the POI. PMID- 27271980 TI - Transient autonomic responses during sustained attention in high and low fit young adults. AB - Maintaining vigilance over long periods of time is especially critical in performing fundamental everyday activities and highly responsible professional tasks (e.g., driving, performing surgery or piloting). Here, we investigated the role of aerobic fitness as a crucial factor related to the vigilance capacity. To this end, two groups of young adult participants (high-fit and low-fit) were compared in terms of reaction time (RT) performance and event-related heart rate responses in a 60' version of the psychomotor vigilance task. The results showed shorter RTs in high-fit participants, but only during the first 24' of the task. Crucially, this period of improved performance was accompanied by a decelerative cardiac response pattern present only in the high-fit group that also disappeared after the first 24'. In conclusion, high aerobic fitness was related to a pattern of transient autonomic responses suggestive of an attentive preparatory state that coincided with improved behavioural performance, and that was sustained for 24'. Our findings highlight the importance of considering the role of the autonomic nervous system reactivity in the relationship between fitness and cognition in general, and sustained attention in particular. PMID- 27271981 TI - Rape Myths and the Cross-Cultural Adaptation of the Illinois Rape Myth Acceptance Scale in China. AB - The study examines the similarities and differences between China and the United States with regard to rape myths. We assessed the individual level of rape myth acceptance among Chinese university students by adapting and translating a widely used measure of rape myth endorsement in the United States, the Illinois Rape Myth Acceptance (IRMA) scale. We assessed whether the IRMA scale would be an appropriate assessment of attitudes toward rape among young adults in China. The sample consisted of 975 Chinese university students enrolled in seven Chinese universities. We used explorative factor analysis to examine the factor structure of the Chinese translation of the IRMA scale. Results suggest that the IRMA scale requires some modification to be employed with young adults in China. Our analyses indicate that 20 items should be deleted, and a five-factor model is generated. We discuss relevant similarities and differences in the factor structure and item loadings between the Chinese Rape Myth Acceptance (CRMA) and the IRMA scales. A revised version of the IRMA, the CRMA, can be used as a resource in rape prevention services and rape victim support services. Future research in China that employs CRMA will allow researchers to examine whether individual's response to rape myth acceptance can predict rape potential and judgments of victim blaming and community members' acceptance of marital rape. PMID- 27271982 TI - Sexual Victimization and Benefit Expectations of Risky Behavior Among Female College Students. AB - Sexual victimization has been shown to positively relate to both engagement in risky behavior and subsequent sexual victimization. Research has focused on the degree to which women consider the risks or costs of engaging in risky behaviors. The purpose of the current study was to examine the degree to which women weigh the costs and benefits of engaging in risky behaviors. Using self-report data from 113 female undergraduates, two separate hierarchical regression analyses were performed to examine the contributions of number of sexual victimization experiences, emotion dysregulation, cost expectations of risky behavior, and benefit expectations of risky behavior to latency to exit a risk perception vignette involving a stranger and frequency of engagement in risky behavior. Regression analyses revealed that the full set of predictors accounted for 13% of the variance in latency to exit the risk perception vignette involving a stranger, with emotion dysregulation and benefit expectations making significant and independent contributions. Regression analyses revealed that the same set of predictors accounted for 34% of the variance in frequency of engagement in risky behavior, with number of sexual victimization experiences and benefit expectations making significant and independent contributions. The current findings suggest that sexual victimization risk may be influenced by perceived benefits of risky behavior. Implications of the current findings will be discussed in the context of sexual victimization risk reduction. PMID- 27271983 TI - Personal and Environmental Predictors of Depression Among Victims of Intimate Partner Violence: Comparison of Immigrant and Israeli-Born Women. AB - In the present study, ecological theory was used as a basis for predicting depression among women who survive intimate partner violence (IPV). The predictors examined in the study derived from three ecological systems: the microsystem (background variables and frequency of the violence), the ontogenic system (personal resources), and the mesosystem (support resources). One hundred twenty-five women who immigrated from the Former Soviet Union and 149 Israeli born Jewish women filled in questionnaires when they entered shelters for victims of IPV. The research findings indicate that background variables, including immigration, did not contribute significantly to the women's depression. Frequency of violence contributed slightly to depression, whereas the women's sense of mastery and social support contributed most significantly. The results highlight the need to strengthen these resources when women are in shelters, and to conduct further research to determine whether these results also hold true for women who receive services for prevention of violence in the community. PMID- 27271984 TI - Giant reversible anisotropy changes at room temperature in a (La,Sr)MnO3/Pb(Mg,Nb,Ti)O3 magneto-electric heterostructure. AB - In a model artificial multiferroic system consisting of a (011)-oriented ferroelectric Pb(Mg,Nb,Ti)O3 substrate intimately coupled to an epitaxial ferromagnetic (La,Sr)MnO3 film, electric field pulse sequences of less than 6 kV/cm induce large, reversible, and bistable remanent strains. The magnetic anisotropy symmetry reversibly switches from a highly anisotropic two-fold state to a more isotropic one, with concomitant changes in resistivity. Anisotropy changes at the scale of a single ferromagnetic domain were measured using X-ray microscopy, with electric-field dependent magnetic domain reversal showing that the energy barrier for magnetization reversal is drastically lowered. Free energy calculations confirm this barrier lowering by up to 70% due to the anisotropic strain changes generated by the substrate. Thus, we demonstrate that an electric field pulse can be used to 'set' and 'reset' the magnetic anisotropy orientation and resistive state in the film, as well as to lower the magnetization reversal barrier, showing a promising route towards electric-field manipulation of multifunctional nanostructures at room temperature. PMID- 27271985 TI - Aneurysm of the cranial mesenteric artery as a site of carriage of Salmonella enterica subsp. enterica serovar Abortusequi in the horse. AB - Salmonella enterica subsp. enterica serovar Abortusequi is a pathogen restricted to horses. Our investigation targeted 4 draft horses (9-10 months old) kept on a Japanese farm that had suffered an outbreak of S. Abortusequi abortion. The 4 horses were suspected to be carriers of the bacterium owing to their high agglutination titers (>=1:2,560) in tube agglutination testing. The owners' on farm observations confirmed that the horses had no apparent abnormalities, and S. Abortusequi was not isolated from their blood, rectal swabs, or sternal bone marrow fluid at antemortem investigation. However, at autopsy, all horses displayed the following: suppurative aneurysm of the cranial mesenteric artery with heavy infection with Strongylus vulgaris larvae; heavy intestinal parasitic infection with Gasterophilus intestinalis, Parascaris equorum, Anoplocephala perfoliata, and S. vulgaris; and enlargement of the systemic lymph nodes. In each case, large numbers of S. Abortusequi were isolated from the anterior mesenteric artery thrombus. The thrombus isolates harbored a single virulence plasmid, and the pulsed-field gel electrophoresis profiles of the isolates were identical not only to each other but also to those of Japanese enzootic strains of S. Abortusequi. These results reveal that parasitic aneurysms of the cranial mesenteric artery should be considered an important possible site of carriage of S. Abortusequi in horses. The results also suggest high clonality of the isolated serovar in the horse population in Japan. PMID- 27271986 TI - Cutaneous pythiosis in a donkey (Equus asinus) in Brazil. AB - Our study describes the clinical, epidemiologic, pathologic, immunohistochemical, and molecular aspects PCR of a case of cutaneous pythiosis in a donkey (Equus asinus) from Brazil. During a dry period, the animal grazed for 4 months around a pond where the vegetation remained green. Skin lesions were nodular, multifocal, and disseminated, mainly involving the legs, ventral chest, and mammary gland. On cut surface, there were multifocal to coalescent discrete yellow foci, and occasional small cavitations with a few kunkers. Ulcerative nodular pyogranulomatous and eosinophilic dermatitis with folliculitis and furunculosis were observed histologically. Hyphae were observed in sections stained with Gomori methenamine silver. Immunohistochemistry with Pythium insidiosum antibodies yielded strong immunostaining of hyphae. P. insidiosum DNA was extracted from tissues in paraffin blocks by amplification of a fragment of 105 bp, which targets the 5.8S ribosomal gene. After the diagnosis of pythiosis, the larger skin lesions were excised and treated as second intention healing wounds, which were completely healed 30 days after resection. Small skin lesions regressed spontaneously in ~60 days. The granulomatous inflammation and outcome of the disease in this donkey were similar to cases of pythiosis in cattle. PMID- 27271987 TI - Neuro-Modulation of Immuno-Endocrine Response Induced by Kaliotoxin of Androctonus Scorpion Venom. AB - Kaliotoxin (KTX), a specific blocker of potassium channels, exerts various toxic effects due to its action on the central nervous system. Its use in experimental model could help the understanding of the cellular and molecular mechanisms involved in the neuropathological processes related to potassium channel dysfunctions. In this study, the ability of KTX to stimulate neuro-immuno endocrine axis was investigated. As results, the intracerebroventricular injection of KTX leads to severe structural-functional alterations of both hypothalamus and thyroid. These alterations were characterized by a massive release of hormones' markers of thyroid function associated with damaged tissue which was infiltrated by inflammatory cell and an imbalanced redox status. Taken together, these data highlight that KTX is able to modulate the neuro-endocrine response after binding to its targets leading to the hypothalamus and the thyroid stimulation, probably by inflammatory response activation and the installation of oxidative stress in these organs. PMID- 27271988 TI - Cytosolic DNA Sensor Upregulation Accompanies DNA Electrotransfer in B16.F10 Melanoma Cells. AB - In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptors or DNA sensors in response to DNA electrotransfer. In tumors, IFNbeta mRNA and protein levels significantly increased. The mRNAs of several DNA sensors were detected, and DAI, DDX60, and p204 tended to be upregulated. These effects were accompanied with reduced tumor growth and increased tumor necrosis. In B16.F10 cells in culture, IFNbeta mRNA and protein levels were significantly upregulated. The mRNAs for several DNA sensors were present in these cells; DNA dependent activator of interferon regulatory factor (DAI), DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 (DDX60), and p204 were significantly upregulated while DDX60 protein levels were coordinately upregulated. Upregulation of DNA sensors in tumors could be masked by the lower transfection efficiency compared to in vitro or to dilution by other tumor cell types. Mirroring the observation of tumor necrosis, cells underwent a significant DNA concentration-dependent decrease in proliferation and survival. Taken together, these results indicate that DNA electrotransfer may cause the upregulation of several intracellular DNA sensors in B16.F10 cells, inducing effects in vitro and potentially in vivo. PMID- 27271989 TI - Serum microRNA panels as potential biomarkers for early detection of hepatocellular carcinoma on top of HCV infection. AB - The identification of new high-sensitivity and high-specificity markers for hepatocellular carcinoma (HCC) is essential. We aimed at identifying serum microRNAs (miRNAs) as potential biomarkers for early detection of HCC on top hepatitis C virus (HCV) infection. We investigated serum expression of 13 miRNAs in 384 patients with HCV-related chronic liver disease (192 with HCC, 96 with liver cirrhosis (LC), and 96 with chronic hepatitis C (CHC)) in addition to 96 healthy participants enrolled as a control group. The miRNA expression was performed using real-time quantitative PCR-based SYBR Green custom miRNA arrays. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of miRNA panels for early detection of HCC. Using miRNA panel of miR-122, miR-885-5p, and miR-29b with alpha fetoprotein (AFP) provided high diagnostic accuracy (AUC = 1) for early detection of HCC in normal population while using miRNA panel of miR-122, miR-885-5p, miR-221, and miR-22 with AFP provided high diagnostic accuracy (AUC = 0.982) for early detection of HCC in LC patients. However, using miRNA panel of miR-22 and miR 199a-3p with AFP provided high diagnostic accuracy (AUC = 0.988) for early detection of HCC in CHC patients. We identified serum miRNA panels that could have a considerable clinical use in early detection of HCC in both normal population and high-risk patients. PMID- 27271990 TI - High alpha-methylacyl-CoA racemase (AMACR) is associated with ERG expression and with adverse clinical outcome in patients with localized prostate cancer. AB - Alpha-methylacyl-CoA racemase (AMACR) is a well-characterized marker extensively utilized in prostate cancer (PCA) diagnosis. However, the prognostic value of AMACR expression and its relation to TMPRSS2-ERG gene rearrangement as one of the most common molecular alterations in PCA is not fully explored. AMACR expression was investigated in a cohort of 218 men with localized PCA treated by radical prostatectomy and correlated with ERG and various clinical and pathological parameters. In vitro studies assessed AMACR changes to ERG knockdown and other related genes. In addition, bioinformatics validated the significance of AMACR/ERG expression and assessed relevant genetic signatures in relation to AMACR/ERG expression. AMACR expression was significantly associated with disease progression and with ERG (p ~0). Seventeen percent of cancer foci showed negative/weak AMACR expression while being ERG positive. High AMACR expression was significantly associated with positive surgical margins (p = 0.01), specifically in tumors with lower Gleason score <7, with ~95 % exhibiting positive surgical margin (p = 0.008). High AMACR showed marginal association with PSA biochemical recurrence (BCR) (p = 0.06) which was slightly more pronounced in ERG-positive tumors (p = 0.04). This was validated in other public cohorts. However, in this cohort, the association with BCR was not statistically significant in multivariate analysis (p = 0.09). Using in vitro cellular models, AMACR messenger RNA (mRNA) expression, but not protein levels, showed an association with ERG expression. We report for the first time a significant association between AMACR and ERG with prognostic implication. Patients with high AMACR/ERG-positive PCA may be at higher risk for disease progression, and additional studies in larger cohorts are needed to confirm the above findings. Functional studies investigating the molecular pathways connecting AMACR and ERG may provide an additional insight into PCA progression pathways. PMID- 27271991 TI - Simulations on the influence of myelin water in diffusion-weighted imaging. AB - While myelinated axons present an important barrier to water diffusion, many models used to interpret DWI signal neglect other potential influences of myelin. In this work, Monte Carlo simulations were used to test the sensitivity of DWI results to the diffusive properties of water within myelin. Within these simulations, the apparent diffusion coefficient (D app) varied slowly over several orders of magnitude of the coefficient of myelin water diffusion (D m), but exhibited important differences compared to D app values simulated that neglect D m (=0). Compared to D app, the apparent diffusion kurtosis (K app) was generally more sensitive to D m. Simulations also tested the sensitivity of D app and K app to the amount of myelin present. Unique variations in D app and K app caused by differences in the myelin volume fraction were diminished when myelin water diffusion was included. Also, expected trends in D app and K app with experimental echo time were reduced or inverted when accounting for myelin water diffusion, and these reduced/inverted trends were seen experimentally in ex vivo rat brain DWI experiments. In general, myelin water has the potential to subtly influence DWI results and bias models of DWI that neglect these components of white matter. PMID- 27271992 TI - Melanopsin-mediated post-illumination pupil response in the peripheral retina. AB - Intrinsically photosensitive retinal ganglion cells (ipRGCs) regulate pupil size by integrating extrinsic rod and cone signals with intrinsic melanopsin-mediated phototransduction. Light adapted pupil diameter is determined by the corneal flux density (CFD), and for central visual field stimulation the melanopsin-mediated post-illumination pupil response (PIPR) follows this same CFD relationship. Rods, cones, and ipRGCs vary in size, density, and distribution across the retina, but how these differences affect the amplitude and timing of the extrinsic and intrinsic pupil light reflex in the central and peripheral retina is unknown. We determined the relationship between stimulus area and photon flux with stimuli constant for CFD, irradiance, or area at central (0 degrees ) and peripheral (20 degrees ) eccentricities with high and low melanopsin excitation. We show that the pupil constriction amplitude was similar at both eccentricities and the time to minimum diameter increased as melanopsin excitation increased. In contrast, the peripheral PIPR follows a CFD relationship but with lower amplitude compared with that at the fovea. This indicates differences in the spatial and temporal characteristics of extrinsic and intrinsic ipRGC inputs to the pupil control pathway for the central and peripheral retina. The eccentricity-dependent change in PIPR amplitude may be analogous to the hill of vision observed in visual perimetry; such knowledge is an important precursor to the development of pupil perimetry paradigms to measure the PIPR in select regions of the visual field. PMID- 27271993 TI - Are face representations depth cue invariant? AB - The visual system can process three-dimensional depth cues defining surfaces of objects, but it is unclear whether such information contributes to complex object recognition, including face recognition. The processing of different depth cues involves both dorsal and ventral visual pathways. We investigated whether facial surfaces defined by individual depth cues resulted in meaningful face representations-representations that maintain the relationship between the population of faces as defined in a multidimensional face space. We measured face identity aftereffects for facial surfaces defined by individual depth cues (Experiments 1 and 2) and tested whether the aftereffect transfers across depth cues (Experiments 3 and 4). Facial surfaces and their morphs to the average face were defined purely by one of shading, texture, motion, or binocular disparity. We obtained identification thresholds for matched (matched identity between adapting and test stimuli), non-matched (non-matched identity between adapting and test stimuli), and no-adaptation (showing only the test stimuli) conditions for each cue and across different depth cues. We found robust face identity aftereffect in both experiments. Our results suggest that depth cues do contribute to forming meaningful face representations that are depth cue invariant. Depth cue invariance would require integration of information across different areas and different pathways for object recognition, and this in turn has important implications for cortical models of visual object recognition. PMID- 27271994 TI - Multivariate Analyses and Classification of Inertial Sensor Data to Identify Aging Effects on the Timed-Up-and-Go Test. AB - Many tests can crudely quantify age-related mobility decrease but instrumented versions of mobility tests could increase their specificity and sensitivity. The Timed-up-and-Go (TUG) test includes several elements that people use in daily life. The test has different transition phases: rise from a chair, walk, 180 degrees turn, walk back, turn, and sit-down on a chair. For this reason the TUG is an often used test to evaluate in a standardized way possible decline in balance and walking ability due to age and or pathology. Using inertial sensors, qualitative information about the performance of the sub-phases can provide more specific information about a decline in balance and walking ability. The first aim of our study was to identify variables extracted from the instrumented timed up-and-go (iTUG) that most effectively distinguished performance differences across age (age 18-75). Second, we determined the discriminative ability of those identified variables to classify a younger (age 18-45) and older age group (age 46-75). From healthy adults (n = 59), trunk accelerations and angular velocities were recorded during iTUG performance. iTUG phases were detected with wavelet analysis. Using a Partial Least Square (PLS) model, from the 72-iTUG variables calculated across phases, those that explained most of the covariance between variables and age were extracted. Subsequently, a PLS-discriminant analysis (DA) assessed classification power of the identified iTUG variables to discriminate the age groups. 27 variables, related to turning, walking and the stand-to-sit movement explained 71% of the variation in age. The PLS-DA with these 27 variables showed a sensitivity and specificity of 90% and 85%. Based on this model, the iTUG can accurately distinguish young and older adults. Such data can serve as a reference for pathological aging with respect to a widely used mobility test. Mobility tests like the TUG supplemented with smart technology could be used in clinical practice. PMID- 27271995 TI - Gonad morphology of Susan's dwarfgoby Eviota susanae. AB - The gonad morphology of a dwarfgoby Eviota susanae was described and compared with other species within the genus. Eviota susanae was found to have a persistent integrated ovotestis form of gonad in which both spermatogenic and oogenic tissue were found interspersed throughout the gonad. This is consistent with previously described species of Eviota, suggesting that gonad morphology is conserved across the genus. PMID- 27271996 TI - The second will be first: competition on directed networks. AB - Multiple sinks competition is investigated for a walker diffusing on directed complex networks. The asymmetry of the imposed spatial support makes the system non transitive. As a consequence, it is always possible to identify a suitable location for the second absorbing sink that screens at most the flux of agents directed against the first trap, whose position has been preliminarily assigned. The degree of mutual competition between pairs of nodes is analytically quantified through apt indicators that build on the topological characteristics of the hosting graph. Moreover, the positioning of the second trap can be chosen so as to minimize, at the same time, the probability of being in turn shaded by a thirdly added trap. Supervised placing of absorbing traps on a asymmetric disordered and complex graph is hence possible, as follows a robust optimization protocol. This latter is here discussed and successfully tested against synthetic data. PMID- 27271998 TI - New Analytical Monographs on TCM Herbal Drugs for Quality Proof. AB - Regardless of specific national drug regulations there is an international consensus that all TCM drugs must meet stipulated high quality standards focusing on authentication, identification and chemical composition. In addition, safety of all TCM drugs prescribed by physicians has to be guaranteed. During the 25 years history of the TCM hospital Bad Kotzting, 171 TCM drugs underwent an analytical quality proof including thin layer as well as high pressure liquid chromatography. As from now mass spectroscopy will also be available as analytical tool. The findings are compiled and already published in three volumes of analytical monographs. One more volume will be published shortly, and a fifth volume is in preparation. The main issues of the analytical procedure in TCM drugs like authenticity, botanical nomenclature, variability of plant species and parts as well as processing are pointed out and possible ways to overcome them are sketched. PMID- 27271997 TI - t-boc synthesis of huwentoxin-i through native chemical ligation incorporating a trifluoromethanesulfonic acid cleavage strategy. AB - Tert-butyloxycarbonyl (t-Boc)-based native chemical ligation (NCL) techniques commonly employ hydrogen fluoride (HF) to create the thioester fragment required for the ligation process. Our research aimed to assess the replacement of HF with Trifluoromethanesulfonic acid (TFMSA). Here we examined a 33 amino acid test peptide, Huwentoxin-I (HwTx-I) as a novel candidate for our TFMSA cleavage protocol. Structurally HwTx-I has an X-Cys(16) -Cys(17) -X sequence mid-region, which makes it an ideal candidate for NCL. Experiments determined that the best yields (16.8%) obtained for 50 mg of a thioester support resin were achieved with a TFMSA volume of 100 MUL with a 0.5-h incubation on ice, followed by 2.0 h at room temperature. RP-HPLC/UV and mass spectra indicated the appropriate parent mass and retention of the cleaved HwTx-I N-terminal thioester fragment (Ala(1) Cys(16) ), which was used in preparation for NCL. The resulting chemically ligated HwTx-I was oxidized/folded, purified, and then assessed for pharmacological target selectivity. Native-like HwTx-I produced by this method yielded an EC50 value of 340.5 +/- 26.8 nM for Nav 1.2 and an EC50 value of 504.1 +/- 81.3 nM for Nav 1.3, this being similar to previous literature results using native material. This article represents the first NCL based synthesis of this potent sodium channel blocker. Our illustrated approach removes potential restrictions in the advancement of NCL as a common peptide laboratory technique with minimal investment, and removes the hazards associated with HF usage. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 737-745, 2016. PMID- 27271999 TI - The role of environment and core-margin effects on range-wide phenotypic variation in a montane grasshopper. AB - The integration of genetic information with ecological and phenotypic data constitutes an effective approach to gain insight into the mechanisms determining interpopulation variability and the evolutionary processes underlying local adaptation and incipient speciation. Here, we use the Pyrenean Morales grasshopper (Chorthippus saulcyi moralesi) as study system to (i) analyse the relative role of genetic drift and selection in range-wide patterns of phenotypic differentiation and (ii) identify the potential selective agents (environment, elevation) responsible for variation. We also test the hypothesis that (iii) the development of dispersal-related traits is associated with different parameters related to population persistence/turnover, including habitat suitability stability over the last 120 000 years, distance to the species distribution core and population genetic variability. Our results indicate that selection shaped phenotypic differentiation across all the studied morphological traits (body size, forewing length and shape). Subsequent analyses revealed that among population differentiation in forewing length was significantly explained by a temperature gradient, suggesting an adaptive response to thermoregulation or flight performance under contrasting temperature regimes. We found support for our hypothesis predicting a positive association between the distance to the species distribution core and the development of dispersal-related morphology, which suggests an increased dispersal capability in populations located at range edges that, in turn, exhibit lower levels of genetic variability. Overall, our results indicate that range-wide patterns of phenotypic variation are partially explained by adaptation in response to local environmental conditions and differences in habitat persistence between core and peripheral populations. PMID- 27272000 TI - The first Team Haemophilia Education meeting, 2015, Amsterdam, The Netherlands. AB - Haemophilia remains a complex disorder to diagnose and manage, requiring close cooperation between multidisciplinary healthcare professionals. There are still many unmet challenges in haemophilia care. The first Team Haemophilia Education (THE) meeting, held on 7-8 May 2015 in Amsterdam, The Netherlands, aimed to promote the optimal care of haemophilia patients through education of the multidisciplinary treatment team. This was achieved by reviewing the latest developments in haemophilia management, considering how these can be implemented in the clinic to improve patient care and providing a platform for networking and debate for all haemophilia treatment team members. Haemophilia treatment centres from several countries were asked to complete a premeeting online questionnaire to establish the biggest challenges that they face when managing patients. The concerns expressed were used to develop the agenda, which comprised a combination of formal presentations, case studies and informal workshops covering such topics as pharmacokinetics, laboratory assays and tailoring of treatment to individual patients. This report is a summary of the key developments in haemophilia care presented by various investigators and healthcare professionals at THE meeting 2015. PMID- 27272001 TI - [Study for the treatment of nonmuscle invasive bladder cancer : A phase III efficacy trial for intravesical instillation of mistletoe extract in superficial bladder cancer (TIM) - AB 40/11 of the AUO]. PMID- 27272002 TI - [German Society of Urology harnesses social media : Hands-on, interaction, and discussions at the annual meeting]. PMID- 27272003 TI - [Effect of the body mass index on outcomes of ureterorenoscopy for renal stones]. AB - BACKGROUND: Purpose of this work is to compare the outcome of ureterorenoscopy (URS) with regard to stone-free rates (SFR) and complication rates (CR) in patients with different body mass index (BMI) scores for the treatment of kidney stones. MATERIALS AND METHODS: A retrospective chart review of all patients with known BMI, who underwent URS for kidney stones between 2006 and 2012 at our institution, was performed (n = 556 patients). The SFR and CR of obese patients were compared to overweight and normal weight patients. RESULTS: Mean age was 52.51 years and the average BMI 27.74 kg/m2. Of the patients, 34.2 % had normal weight (22.59 +/- 1.91 kg/m2), 39.6 % were overweight (27.30 +/- 1.42 kg/m2), and 26.3 % were obese (35.09 +/- 5.93 kg/m2). The mean ASA score differed significantly between normal weight (1.99 +/- 0.57), overweight (2.03 +/- 0.62), and obese (2.22 +/- 0.63) patients (p <= 0.036). The mean stone size was 8.51 +/- 6.84 mm and the mean number of stones per patient 1.9 +/- 2.41, whereby the differences between groups was not significant. There were no differences between the groups regarding the use of preoperative (94.8 %) and postoperative ureteral stents (60.3 %), the Ho:YAG laser (33.6 %), the use of flexible (16.2 %) or semirigid/flexible URS (59.4 %), and the mean operative time (52.04 +/- 34.55 min). There were no differences in the SFR for the upper (90 %), mid (94.7 %), and lower pole (90.2 %), multiple location (68.6 %) or the total SFR (86.3 %). Total SFR of 95.7, 88.4, and 73.7 % for urinary calculi < 5 mm, 5-9 mm, and >= 10 mm, respectively, were found and the differences between the patient groups was not significant. The CR was 10.4 % (differences between the patient groups not significant). CONCLUSION: URS is an appropriate treatment for renal stones with high SFR and low CR regardless of patient's BMI. PMID- 27272004 TI - [Uncommon manifestation of prostate cancer : Sister Mary Joseph's nodule]. AB - We report on the case of an 81-year-old man suffering from prostate cancer for several years. In recent months, PSA levels increased, and 68Ga-PSMA-PET-CT (PSMA: prostate-specific membrane antigen) imaging demonstrated suspicious lesions in the paravesical area and an umbilical tumor mass. Local excision was performed. Histologically, the tumor mass was diagnosed as metastasis of the prostate cancer, which is also designated as Sister Mary Joseph's nodule. Umbilical metastases of primary prostate cancer are extremely rare; however, they are of clinical importance since they are commonly associated with tumor progress and with a particularly poor prognosis. PMID- 27272005 TI - Half-sized liver allografts and half the story. PMID- 27272007 TI - MSLVP: prediction of multiple subcellular localization of viral proteins using a support vector machine. AB - Knowledge of the subcellular location (SCL) of viral proteins in the host cell is important for understanding their function in depth. Therefore, we have developed "MSLVP", a two-tier prediction algorithm for predicting multiple SCLs of viral proteins. For this study, data sets of comprehensive viral proteins with experimentally validated SCL annotation were collected from UniProt. Non redundant (90%) data sets of 3480 viral proteins that belonged to single (2715), double (391) and multiple (374) sites were employed. Additionally, 1687 (30% sequence identity) viral proteins were categorised into single (1366), double (167) and multiple (154) sites. Single, double and multiple locations further comprised of eight, four and six categories, respectively. Viral protein locations include the nucleus, cytoplasm, endoplasmic reticulum, extracellular, single-pass membrane, multi-pass membrane, capsid, remaining others and combinations thereof. Support vector machine based models were developed using sequence features like amino acid composition, dipeptide composition, physicochemical properties and their hybrids. We have employed "one-versus-one" as well as "one-versus-other" strategies for multiclass classification. The performance of "one-versus-one" is better than the "one-versus-other" approach during 10-fold cross-validation. For the 90% data set, we achieved an accuracy, a Matthew's correlation coefficient (MCC) and a receiver operating characteristic (ROC) of 99.99%, 1.00, 1.00; 100.00%, 1.00, 1.00 and 99.90%; 1.00, 1.00 for single, double and multiple locations, respectively. Similar results were achieved for a 30% sequence identity data set. Predictive models for each SCL performed equally well on the independent dataset. The MSLVP web server () can predict subcellular locations i.e. single (8; including single and multi-pass membrane), double (4) and multiple (6). This would be helpful for elucidating the functional annotation of viral proteins and potential drug targets. PMID- 27272006 TI - The growth and reproduction performance of TALEN-mediated beta-lactoglobulin knockout bucks. AB - With the technological development of several engineered endonucleases (EENs), such as zinc-finger nucleases, transcription activator-like effector nucleases (TALENs) and CRISPR/Cas9, gene targeting by homologous recombination has been efficiently improved to generate site-specifically genetically modified livestock. However, few studies have been done to investigate the health and fertility of these animals. The purpose of the present study is to investigate if gene targeting events and a recloning procedure would affect the production traits of EEN-mediated gene targeted bucks. TALEN-mediated beta-lactoglobulin (BLG) gene mono-allelic knockout (BLG (+/-)) goats and bi-allelic knockout (BLG ( /-)) buck produced by using sequential gene targeting combined with recloning in fibroblasts from BLG (+/-) buck were used to evaluate their health and fertility. Birth weight and postnatal growth of BLG (+/-) bucks were similar to the wild type goats. None of the parameters for both fresh and frozen-thawed semen quality were significantly different in BLG (+/-) or BLG (-/-) bucks compared to their corresponding comparators. In vitro fertilization (IVF) test revealed that the proportion of IVF oocytes developing to the blastocyst stage was identical among BLG (+/-), BLG (-/-) and wild-type bucks. Conception rates of artificial insemination were respectively 42.3, 38.0 and 42.6 % for frozen-thawed semen from the BLG (+/-), BLG (-/-) and wild-type bucks. In addition, germline transmission of the targeted BLG modification was in accordance with Mendelian rules. These results demonstrated that the analyzed growth and reproductive traits were not impacted by targeting BLG gene and recloning, implicating the potential for dairy goat breeding of BLG (+/-) and BLG (-/-) bucks. PMID- 27272008 TI - (19) F NMR Spectroscopy as a Highly Sensitive Method for the Direct Monitoring of Confined Crystallization within Nanoporous Materials. AB - The introduction of fluorine into the structure of pharmaceuticals has been an effective strategy for tuning their pharmacodynamic properties, with more than 40 new drugs entering the market in the last 15 years. In this context, (19) F NMR spectroscopy can be viewed as a useful method for investigating the host-guest chemistry of pharmaceuticals in nanosized drug-delivery systems. Although the interest in confined crystallization, nanosized devices, and porous catalysts is gradually increasing, understanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking. Using (19) F magic-angle-spinning NMR spectroscopy, we obtained detailed mechanistic insight into the crystallization of flufenamic acid (FFA) in a confined environment of mesoporous silica materials with different pore diameters (3.2-29 nm), providing direct experimental evidence for the formation of a molecular liquid-like layer besides crystalline confined FFA form I. PMID- 27272010 TI - Analysis of miRNAs and their target genes associated with lipid metabolism in duck liver. AB - Fat character is an important index in duck culture that linked to local flavor, feed cost and fat intake for costumers. Since the regulation networks in duck lipid metabolism had not been reported very clearly, we aimed to explore the potential miRNA-mRNA pairs and their regulatory roles in duck lipid metabolism. Here, Cherry-Valley ducks were selected and treated with/without 5% oil added in feed for 2 weeks, and then fat content determination was performed on. The data showed that the fat contents and the fatty acid ratios of C17:1 and C18:2 were up regulated in livers of oil-added ducks, while the C12:0 ratio was down-regulated. Then 21 differential miRNAs, including 10 novel miRNAs, were obtain from the livers by sequencing, and 73 target genes involved in lipid metabolic processes of these miRNAs were found, which constituted 316 miRNA-mRNA pairs. Two miRNA mRNA pairs including one novel miRNA and one known miRNA, N-miR-16020-FASN and gga-miR-144-ELOVL6, were selected to validate the miRNA-mRNA negative relation. And the results showed that N-mir-16020 and gga-miR-144 could respectively bind the 3'-UTRs of FASN and ELOVL6 to control their expressions. This study provides new sights and useful information for future research on regulation network in duck lipid metabolism. PMID- 27272013 TI - Lack of glucuronidation products of trans-resveratrol in plasma and urine of cats. AB - Resveratrol has generated interest in cats due to reported health benefits. Cats have low activity of beta-glucuronidase, and we hypothesized they could not form two common resveratrol metabolites, resveratrol-3-O-glucuronide and resveratrol 4'-O-glucuronide. Resveratrol, 3 mg/cat/day, was given orally to intact male (n = 5) and female cats (n = 5) for 4 weeks. A control group (8 intact males) was used for comparison. Plasma and urine were collected weekly and analysed using high pressure liquid chromatography coupled with tandem mass spectrometry. Resveratrol and resveratrol-3-O-sulphate, but no glucuronide metabolites, were detected in plasma and urine. Median (range 10-90th percentile) plasma resveratrol for control and treatment groups was 0.46 ng/ml (0.02-1.74 ng/ml) and 0.96 ng/ml (0.65-3.21 ng/ml). Median (range) plasma resveratrol-3-O-sulphate for control and treatment groups was 6.32 ng/ml (2.55-10.29 ng/ml) and 11.45 ng/ml (1.47-53.29 ng/ml). Plasma resveratrol differed from control in week 4, while plasma resveratrol-3-O-sulphate was different in all weeks (p < 0.05). Median (range) urine resveratrol for control and treatment groups was 0.28 ng/ml (0.05-1.59 ng/ml) and 19.98 ng/ml (8.44-87.54 ng/ml). Median (range) urine resveratrol-3-O sulphate for control and treatment groups was 26.71 ng/ml (10.50-75.58 ng/ml) and 108.69 ng/ml (11.83-231.05 ng/ml). All time points for urine resveratrol and resveratrol-3-O-sulphate were significantly different from control (p < 0.05), except for weeks 1, 3 and 4 for resveratrol. The results support our hypothesis that cats are unlikely able to glucuronidate resveratrol, most likely due to a reduction in the activity of beta-glucuronidase. PMID- 27272011 TI - Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome. AB - OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms. METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-gamma, and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed. RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-gamma tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified. CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients. PMID- 27272012 TI - Electromagnetic-Guided Bedside Placement of Nasoenteral Feeding Tubes by Nurses Is Non-Inferior to Endoscopic Placement by Gastroenterologists: A Multicenter Randomized Controlled Trial. AB - OBJECTIVES: Electromagnetic (EM)-guided bedside placement of nasoenteral feeding tubes by nurses may improve efficiency and reduce patient discomfort and costs compared with endoscopic placement by gastroenterologists. However, evidence supporting this task shift from gastroenterologists to nurses is limited. We aimed to compare the effectiveness of EM-guided and endoscopic nasoenteral feeding tube placement. METHODS: We performed a multicenter randomized controlled non-inferiority trial in 154 adult patients who required nasoenteral feeding and were admitted to gastrointestinal surgical wards in five Dutch hospitals. Patients were randomly assigned (1:1) to undergo EM-guided or endoscopic nasoenteral feeding tube placement. The primary end point was the need for reinsertion of the feeding tube (e.g., after failed initial placement or owing to tube-related complications) with a prespecified non-inferiority margin of 10%. RESULTS: Reinsertion was required in 29 (36%) of the 80 patients in the EM-guided group and 31 (42%) of the 74 patients in the endoscopy group (absolute risk difference -6%, upper limit of one-sided 95% confidence interval 7%; P for non inferiority=0.022). No differences were noted in success and complication rates. In the EM-guided group, there was a reduced time to start of feeding (424 vs. 535 min, P=0.001). Although the level of discomfort was higher in the EM-guided group (Visual Analog Scale (VAS) 3.9 vs. 2.0, P=0.009), EM-guided placement received higher recommendation scores (VAS 8.2 vs. 5.5, P=0.008). CONCLUSIONS: EM-guided bedside placement of nasoenteral feeding tubes by nurses was non-inferior to endoscopic placement by gastroenterologists in surgical patients and may be considered the preferred technique for nasoenteral feeding tube placement. PMID- 27272014 TI - Repeated evolution of amphibious behavior in fish and its implications for the colonization of novel environments. AB - We know little about on how frequently transitions into new habitats occur, especially the colonization of novel environments that are the most likely to instigate adaptive evolution. One of the most extreme ecological transitions has been the shift in habitat associated with the move from water to land by amphibious fish. We provide the first phylogenetic investigation of these transitions for living fish. Thirty-three families have species reported to be amphibious and these are likely independent evolutionary origins of fish emerging onto land. Phylogenetic reconstructions of closely related taxa within one of these families, the Blenniidae, inferred as many as seven convergences on a highly amphibious lifestyle. Taken together, there appear to be few constraints on fish emerging onto land given amphibious behavior has evolved repeatedly many times across ecologically diverse families. The colonization of novel habitats by other taxa resulting in less dramatic changes in environment should be equally, if not, more frequent in nature, providing an important prerequisite for subsequent adaptive differentiation. PMID- 27272016 TI - Managing Carbon on Federal Public Lands: Opportunities and Challenges in Southwestern Colorado. AB - Federal lands in the United States have been identified as important areas where forests could be managed to enhance carbon storage and help mitigate climate change. However, there has been little work examining the context for decision making for carbon in a multiple-use public land environment, and how science can support decision making. This case study of the San Juan National Forest and the Bureau of Land Management Tres Rios Field Office in southwestern Colorado examines whether land managers in these offices have adequate tools, information, and management flexibility to practice effective carbon stewardship. To understand how carbon was distributed on the management landscape we added a newly developed carbon map for the SJNF-TRFO area based on Landsat TM texture information (Kelsey and Neff in Remote Sens 6:6407-6422. doi: 10.3390/rs6076407 , 2014). We estimate that only about 22 % of the aboveground carbon in the SJNF TRFO is in areas designated for active management, whereas about 38 % is in areas with limited management opportunities, and 29 % is in areas where natural processes should dominate. To project the effects of forest management actions on carbon storage, staff of the SJNF are expected to use the Forest Vegetation Simulator (FVS) and extensions. While identifying FVS as the best tool generally available for this purpose, the users and developers we interviewed highlighted the limitations of applying an empirically based model over long time horizons. Future research to improve information on carbon storage should focus on locations and types of vegetation where carbon management is feasible and aligns with other management priorities. PMID- 27272017 TI - Setting Priorities for Monitoring and Managing Non-native Plants: Toward a Practical Approach. AB - Land managers face the challenge to set priorities in monitoring and managing non native plant species, as resources are limited and not all non-natives become invasive. Existing frameworks that have been proposed to rank non-native species require extensive information on their distribution, abundance, and impact. This information is difficult to obtain and often not available for many species and regions. National watch or priority lists are helpful, but it is questionable whether they provide sufficient information for environmental management on a regional scale. We therefore propose a decision tree that ranks species based on more simple albeit robust information, but still provides reliable management recommendations. To test the decision tree, we collected and evaluated distribution data from non-native plants in highland grasslands of Southern Brazil. We compared the results with a national list from the Brazilian Invasive Species Database for the state to discuss advantages and disadvantages of the different approaches on a regional scale. Out of 38 non-native species found, only four were also present on the national list. If management would solely rely on this list, many species that were identified as spreading based on the decision tree would go unnoticed. With the suggested scheme, it is possible to assign species to active management, to monitoring, or further evaluation. While national lists are certainly important, management on a regional scale should employ additional tools that adequately consider the actual risk of non-natives to become invasive. PMID- 27272018 TI - Radiographic Blind Test of Curvature of the Posterior Border of the Mandibular Ramus as a Morphological Indicator of Gender. AB - PURPOSE: Curvature of the posterior border of the mandibular ramus at the occlusal plane has been described as a morphological trait for males. Controversy over the accuracy of this method remains among researchers; studies employing similar methods report accuracy rates for successful gender identification ranging from 59% to 99%. This blind study assessed evaluators' ability to determine gender based on the presence or absence of curvature of the posterior margin of the mandibular ramus through panoramic radiographs. MATERIALS AND METHODS: Randomly selected panoramic radiographs were obtained from The Ohio State University College of Dentistry for 413 adult male (M) and female (F) subjects. Two evaluators separately assigned ratings using a similar method to the Loth and Henenberg methodology to each subject on the right and left sides of mandibular rami. The ratings were based upon three criteria: (1) presence of curvature at the occlusal plane (M), (2) presence of curvature but not at the occlusal plane (F), and (3) lack of curvature (F). Pearson exact chi-squared test was used to evaluate the statistical strength of the ratings. RESULTS: The evaluators were only in agreement for both the right and left rami in roughly two thirds (66.8%) of cases when there was no excessive tooth loss (ETL); however, the inter-observer agreement improved to 82.1% for those rami associated with ETL. Inter-observer agreement occurred in 72.9% of female rami and in only 64.4% of male rami. CONCLUSION: The results of this study indicated that assessment of posterior border curvature of mandibular rami through panoramic radiographs was not a reliable indicator of gender and was further plagued by unacceptably high levels of inter-observer disagreement. PMID- 27272015 TI - Structure and calcium-binding studies of calmodulin-like domain of human non muscle alpha-actinin-1. AB - The activity of several cytosolic proteins critically depends on the concentration of calcium ions. One important intracellular calcium-sensing protein is alpha-actinin-1, the major actin crosslinking protein in focal adhesions and stress fibers. The actin crosslinking activity of alpha-actinin-1 has been proposed to be negatively regulated by calcium, but the underlying molecular mechanisms are poorly understood. To address this, we determined the first high-resolution NMR structure of its functional calmodulin-like domain (CaMD) in calcium-bound and calcium-free form. These structures reveal that in the absence of calcium, CaMD displays a conformationally flexible ensemble that undergoes a structural change upon calcium binding, leading to limited rotation of the N- and C-terminal lobes around the connecting linker and consequent stabilization of the calcium-loaded structure. Mutagenesis experiments, coupled with mass-spectrometry and isothermal calorimetry data designed to validate the calcium binding stoichiometry and binding site, showed that human non-muscle alpha-actinin-1 binds a single calcium ion within the N-terminal lobe. Finally, based on our structural data and analogy with other alpha-actinins, we provide a structural model of regulation of the actin crosslinking activity of alpha actinin-1 where calcium induced structural stabilisation causes fastening of the juxtaposed actin binding domain, leading to impaired capacity to crosslink actin. PMID- 27272019 TI - Diacylglycerol kinases activate tobacco NADPH oxidase-dependent oxidative burst in response to cryptogein. AB - Cryptogein is a 10 kDa protein secreted by the oomycete Phytophthora cryptogea that activates defence mechanisms in tobacco plants. Among early signalling events triggered by this microbial-associated molecular pattern is a transient apoplastic oxidative burst which is dependent on the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity of the RESPIRATORY BURST OXIDASE HOMOLOG isoform D (RBOHD). Using radioactive [33 P]-orthophosphate labelling of tobacco Bright Yellow-2 suspension cells, we here provide in vivo evidence for a rapid accumulation of phosphatidic acid (PA) in response to cryptogein because of the coordinated onset of phosphoinositide-dependent phospholipase C and diacylglycerol kinase (DGK) activities. Both enzyme specific inhibitors and silencing of the phylogenetic cluster III of the tobacco DGK family were found to reduce PA production upon elicitation and to strongly decrease the RBOHD-mediated oxidative burst. Therefore, it appears that PA originating from DGK controls NADPH-oxidase activity. Amongst cluster III DGKs, the expression of DGK5-like was up-regulated in response to cryptogein. Besides DGK5-like is likely to be the main cluster III DGK isoform silenced in one of our mutant lines, making it a strong candidate for the observed response to cryptogein. The relevance of these results is discussed with regard to early signalling lipid-mediated events in plant immunity. PMID- 27272020 TI - Computational support for a scaffolding mechanism of centriole assembly. AB - Centrioles are essential for forming cilia, flagella and centrosomes. Successful centriole assembly requires proteins of the SAS-6 family, which can form oligomeric ring structures with ninefold symmetry in vitro. While important progress has been made in understanding SAS-6 protein biophysics, the mechanisms enabling ring formation in vivo remain elusive. Likewise, the mechanisms by which a nascent centriole forms near-orthogonal to an existing one are not known. Here, we investigate possible mechanisms of centriole assembly using coarse-grained Brownian dynamics computer simulations in combination with a rate equation approach. Our results suggest that without any external factors, strong stabilization associated with ring closure would be needed to enable efficient ring formation. Strikingly, our simulations reveal that a scaffold-assisted assembly mechanism can trigger robust ring formation owing to local cooperativity, and that this mechanism can also impart orthogonalilty to centriole assembly. Overall, our findings provide novel insights into the organizing principles governing the assembly of this important organelle. PMID- 27272024 TI - 2-Methylresorcinarene: a very high packing coefficient in a mono-anion based dimeric capsule and the X-ray crystal structure of the tetra-anion. AB - Mono- and tetra-deprotonated 2-methylresorcinarene anions ( and ) as their trans 1,4-diammoniumcyclohexane inclusion complexes are reported. The mono-anion forms a fully closed dimeric capsule [.H2O.MeOH]2(2-) with a cavity volume of 165 A(3) and as the guest with an extremely high packing coefficient, PC = 84.2%, while the tetra-anion forms a close-packed structure with two structurally isomeric tetra-anions and with a 50 : 50 ratio in the crystal lattice. PMID- 27272021 TI - The interplay between effector binding and allostery in an engineered protein switch. AB - The protein design rules for engineering allosteric regulation are not well understood. A fundamental understanding of the determinants of ligand binding in an allosteric context could facilitate the design and construction of versatile protein switches and biosensors. Here, we conducted extensive in vitro and in vivo characterization of the effects of 285 unique point mutations at 15 residues in the maltose-binding pocket of the maltose-activated beta-lactamase MBP317-347. MBP317-347 is an allosteric enzyme formed by the insertion of TEM-1 beta lactamase into the E. coli maltose binding protein (MBP). We find that the maltose-dependent resistance to ampicillin conferred to the cells by the MBP317 347 switch gene (the switch phenotype) is very robust to mutations, with most mutations slightly improving the switch phenotype. We identified 15 mutations that improved switch performance from twofold to 22-fold, primarily by decreasing the catalytic activity in the absence of maltose, perhaps by disrupting interactions that cause a small fraction of MBP in solution to exist in a partially closed state in the absence of maltose. Other notable mutations include K15D and K15H that increased maltose affinity 30-fold and Y155K and Y155R that compromised switching by diminishing the ability of maltose to increase catalytic activity. The data also provided insights into normal MBP physiology, as select mutations at D14, W62, and F156 retained high maltose affinity but abolished the switch's ability to substitute for MBP in the transport of maltose into the cell. The results reveal the complex relationship between ligand binding and allostery in this engineered switch. PMID- 27272026 TI - Correction: Rapid Quantification of 3D Collagen Fiber Alignment and Fiber Intersection Correlations with High Sensitivity. AB - [This corrects the article DOI: 10.1371/journal.pone.0131814.]. PMID- 27272025 TI - Population structure of eleven Spanish ovine breeds and detection of selective sweeps with BayeScan and hapFLK. AB - The goals of the current work were to analyse the population structure of 11 Spanish ovine breeds and to detect genomic regions that may have been targeted by selection. A total of 141 individuals were genotyped with the Infinium 50 K Ovine SNP BeadChip (Illumina). We combined this dataset with Spanish ovine data previously reported by the International Sheep Genomics Consortium (N = 229). Multidimensional scaling and Admixture analyses revealed that Canaria de Pelo and, to a lesser extent, Roja Mallorquina, Latxa and Churra are clearly differentiated populations, while the remaining seven breeds (Ojalada, Castellana, Gallega, Xisqueta, Ripollesa, Rasa Aragonesa and Segurena) share a similar genetic background. Performance of a genome scan with BayeScan and hapFLK allowed us identifying three genomic regions that are consistently detected with both methods i.e. Oar3 (150-154 Mb), Oar6 (4-49 Mb) and Oar13 (68-74 Mb). Neighbor-joining trees based on polymorphisms mapping to these three selective sweeps did not show a clustering of breeds according to their predominant productive specialization (except the local tree based on Oar13 SNPs). Such cryptic signatures of selection have been also found in the bovine genome, posing a considerable challenge to understand the biological consequences of artificial selection. PMID- 27272027 TI - OPTIMISATION IN X-RAY AND MOLECULAR IMAGING 2015 - THE 4th MALMo CONFERENCE ON MEDICAL IMAGING: List of participants. PMID- 27272028 TI - Afterthoughts and Foresight: Digging Through Boxes of Bygone Beliefs and Brooding About the Burgeoning of Bioethics. PMID- 27272029 TI - The Effect of Vibration Treatments Combined with Teriparatide or Strontium Ranelate on Bone Healing and Muscle in Ovariectomized Rats. AB - The aim of the present study was to study the effect of combined therapy of teriparatide (PTH) or strontium ranelate (SR) with whole-body vibration (WBV) on bone healing and muscle properties in an osteopenic rat model. Seventy-two rats (3 months old) were bilaterally ovariectomized (Ovx), and 12 rats were left intact (Non-Ovx). After 8 weeks, bilateral transverse osteotomy was performed at the tibia metaphysis in all rats. Thereafter, Ovx rats were divided into six groups (n = 12): (1) Ovx-no treatment, (2) Ovx + vibration (Vib), (3) SR, (4) SR + Vib, (5) PTH, and (6) PTH + Vib. PTH (40 MUg/kg BW sc. 5*/week) and SR (613 mg/kg BW in food daily) were applied on the day of ovariectomy, vibration treatments 5 days later (vertical, 70 Hz, 0.5 mm, 2*/day for 15 min) for up to 6 weeks. In the WBV + SR group, the callus density, trabecular number, and Alp and Oc gene expression were decreased compared to SR alone. In the WBV + PTH group, the cortical and callus widths, biomechanical properties, Opg gene expression, and Opg/Rankl ratio were increased; the cortical and callus densities were decreased compared to PTH alone. A case of non-bridging was found in both vibrated groups. Vibration alone did not change the bone parameters; PTH possessed a stronger effect than SR therapy. In muscles, combined therapies improved the fiber size of Ovx rats. WBV could be applied alone or in combination with anti-osteoporosis drug therapy to improve muscle tissue. However, in patients with fractures, anti-osteoporosis treatments and the application of vibration could have an adverse effect on bone healing. PMID- 27272030 TI - Low Relative Lean Mass is Associated with Increased Likelihood of Abdominal Aortic Calcification in Community-Dwelling Older Australians. AB - Age-related loss of skeletal muscle is associated with increased risk of functional limitation and cardiovascular (CV) mortality. In the elderly abdominal aortic calcification (AAC) can increase CV risk by altering aortic properties which may raise blood pressure and increase cardiac workload. This study investigated the association between low muscle mass and AAC in community dwelling older Australians. Data for this cross-sectional analysis were drawn from a 2010 sub-study of the Melbourne Collaborative Cohort Study in the setting of community-dwelling older adults. Three hundred and twenty-seven participants [mean age = 71 +/- 6 years; mean BMI = 28 +/- 5 kg/m(2); females n = 199 (62 %)] had body composition determined by dual-energy x-ray absorptiometry (DXA) and AAC determined by radiography. Participants were stratified into tertiles of sex specific BMI-normalised appendicular lean mass (ALM). Those in the lowest tertile were considered to have low relative muscle mass. Aortic calcification score (ACS) was determined visually as the extent of calcification on the aortic walls between L1 and L4 vertebrae (range: 0-24). Severe AAC was defined as ACS >= 6. Prevalence of any AAC was highest in participants with low relative muscle mass (74 %) compared to the middle (65 %) and upper (53 %) tertiles (p trend = 0.006). The lower ALM/BMI tertile had increased odds (Odds ratio = 2.3; 95 % confidence interval: 1.1-4.6; p = 0.021) of having any AAC; and having more severe AAC (2.2; 1.2-4.0; p = 0.009) independent of CV risk factors, serum calcium and physical activity. AAC is more prevalent and severe in community-dwelling older adults with low relative muscle mass. Maintaining muscle mass could form part of a broader primary prevention strategy in reducing AAC. PMID- 27272031 TI - Validity of the Japanese version of functional assessment of cancer therapy gastric (FACT-Ga) and its sensitivity to ascites volume change: a retrospective analysis of Japanese clinical trial participants. AB - PURPOSE: The functional assessment of cancer therapy-gastric (FACT-Ga) questionnaire was designed to evaluate quality of life (QOL) in patients with gastric cancer. We aimed to explore the reliability and validity of FACT-Ga in Japanese patients, and assess the sensitivity of the gastric cancer subscale for detecting changes in cancer-related variables over time. METHODS: The Japanese version of FACT-Ga was used, and data were obtained from Japanese patients who participated in either of two clinical trials: treatment for advanced or recurrent gastric cancer with ascites (advanced-GC group), or adjuvant chemotherapy after curative resection of gastric cancer (adjuvant group). Psychometric data including data used to determine reliability, internal consistency, and clinical validity were analyzed. Clinical validity was evaluated by comparing subscale scores for patients in the two groups, and by comparing subscale scores for patients with different performance status scores. Correlation between gastric cancer subscale scores and gastric cancer-related variables was also examined. In addition, sensitivity of the gastric cancer subscale to changes in ascites volume, abdominal girth, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) was examined by evaluating their correlation in the advanced-GC group. RESULTS: We collected data on 156 patients (62 advanced-GC group patients and 94 adjuvant group patients). Response rates for the subscales were over 80 % at most time points for both the groups. Cronbach's coefficient alpha revealed good internal consistency for each subscale. At baseline, the adjuvant group had higher QOL scores than the advanced GC group (P < 0.05), and QOL scores for patients with different performance status scores differed significantly. Changes in gastric cancer subscale scores showed statistically significant correlation with changes in ascites volume (Spearman's rank correlation coefficient, 0.5; P < 0.05). CONCLUSIONS: FACT-Ga is reliable and clinically valid for Japanese patients with gastric cancer. Detection of QOL changes that correlate with ascites volume changes suggests that it could be used more broadly; FACT-Ga scores could be used as an endpoint for patients with gastric cancer-related ascites. PMID- 27272033 TI - Experimental treatments for poststroke disability: Hasten slowly. PMID- 27272032 TI - Use of Statins and the Risk of Incident Diabetes: A Retrospective Cohort Study. AB - INTRODUCTION: Even though several landmark statin trials have demonstrated the beneficial effects of statin therapy in both primary and secondary prevention of cardiovascular disease, several studies have suggested that statins are associated with a moderate increase in risk of new-onset diabetes. These observations prompted the US FDA to revise statin labels to include a warning of an increased risk of incident diabetes mellitus as a result of increases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose. However, few studies have used US-based data to investigate this statin-associated increased risk of diabetes. OBJECTIVE: The primary objective of our study was to examine whether the use of statins increases the risk of incident diabetes mellitus using data from the Thomson Reuters MarketScan ((r)) Commercial Claims and Encounters Database. METHOD: This study was a retrospective cohort analysis utilizing data for the period 2003-2004. The study population included new statin users aged 20 63 years at index who did not have a history of diabetes. RESULTS: The proportion (3.4 %) of statin users (N = 53,212) who had incident diabetes was higher than the proportion (1.2 %) of non-statin users (N = 53,212) who had incident diabetes. Compared with no statin use and controlling for demographic and clinical covariates, statin use was significantly associated with increased risk of incident diabetes (hazard ratio 2.01; 99 % confidence interval 1.74-2.33; p < 0.0001). In addition, risk of diabetes was highest among users of lovastatin, atorvastatin, simvastatin, and fluvastatin. Diabetes risk was lowest among pravastatin and rosuvastatin users. DISCUSSION: Because the potential for diabetogenicity differs among different statin types, healthcare professionals should individualize statin therapy by identifying patients who would benefit more from less diabetogenic statin types. PMID- 27272034 TI - Practice advisory: Etanercept for poststroke disability: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. AB - OBJECTIVE: To review evidence regarding the effectiveness, safety, and tolerability of etanercept used to treat patients with poststroke disability. METHODS: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for studies of adult patients with poststroke disability treated with etanercept in order to improve their functional status. We rated each study for risk of bias (Class I-IV) using the American Academy of Neurology therapeutic classification of evidence scheme. Practice recommendations were formulated on the basis of the strength of the evidence and assessments of potential benefits, potential harms, and patient preferences. RESULTS: Two case series were identified, and both reported clinical improvements 3 weeks following treatment across a wide range of functional domains. However, both studies were rated Class IV because of poor methodologic quality (i.e., high risk of bias). CONCLUSIONS: For patients with poststroke disability, the evidence is insufficient to support or refute a benefit of etanercept for the treatment of poststroke disability. RECOMMENDATIONS: Clinicians should counsel patients considering etanercept for treatment of poststroke disability that the evidence is insufficient to determine the treatment's effectiveness and that it may be associated with adverse outcomes and high cost (Level U). PMID- 27272035 TI - X-linked adrenoleukodystrophy presenting with positional downbeat nystagmus. PMID- 27272036 TI - Overdiagnosis of idiopathic intracranial hypertension. PMID- 27272037 TI - CLIPPERS with diffuse white matter and longitudinally extensive spinal cord involvement. PMID- 27272038 TI - Clinical Reasoning: Myriad manifestations of a global infectious disease. PMID- 27272039 TI - Pearls & Oy-sters: Episodic ataxia type 2: Case report and review of the literature. PMID- 27272040 TI - Teaching NeuroImages: Posterior reversible encephalopathy syndrome resulting in hydrocephalus. PMID- 27272041 TI - Teaching NeuroImages: Spectrum of paradural dissections of the vertebral artery. PMID- 27272043 TI - Gendist: An R Package for Generated Probability Distribution Models. AB - In this paper, we introduce the R package gendist that computes the probability density function, the cumulative distribution function, the quantile function and generates random values for several generated probability distribution models including the mixture model, the composite model, the folded model, the skewed symmetric model and the arc tan model. These models are extensively used in the literature and the R functions provided here are flexible enough to accommodate various univariate distributions found in other R packages. We also show its applications in graphing, estimation, simulation and risk measurements. PMID- 27272042 TI - Characterisation of the Novel Mixed Mu-NOP Peptide Ligand Dermorphin-N/OFQ (DeNo). AB - INTRODUCTION: Opioid receptors are currently classified as Mu (MU), Delta (delta), Kappa (kappa) plus the opioid related nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP). Despite compelling evidence for interactions and benefits of targeting more than one receptor type in producing analgesia, clinical ligands are Mu agonists. In this study we have designed a Mu-NOP agonist named DeNo. The Mu agonist component is provided by dermorphin, a peptide isolated from the skin of Phyllomedusa frogs and the NOP component by the endogenous agonist N/OFQ. METHODS: We have assessed receptor binding profile of DeNo and compared with dermorphin and N/OFQ. In a series of functional screens we have assessed the ability to (i) increase Ca2+ in cells coexpressing recombinant receptors and a the chimeric protein Galphaqi5, (ii) stimulate the binding of GTPgamma[35S], (iii) inhibit cAMP formation, (iv) activate MAPKinase, (v) stimulate receptor-G protein and arrestin interaction using BRET, (vi) electrically stimulated guinea pig ileum (gpI) assay and (vii) ability to produce analgesia via the intrathecal route in rats. RESULTS: DeNo bound to Mu (pKi; 9.55) and NOP (pKi; 10.22) and with reasonable selectivity. This translated to increased Ca2+ in Galphaqi5 expressing cells (pEC50 Mu 7.17; NOP 9.69), increased binding of GTPgamma[35S] (pEC50 Mu 7.70; NOP 9.50) and receptor-G protein interaction in BRET (pEC50 Mu 8.01; NOP 9.02). cAMP formation was inhibited and arrestin was activated (pEC50 Mu 6.36; NOP 8.19). For MAPK DeNo activated p38 and ERK1/2 at Mu but only ERK1/2 at NOP. In the gpI DeNO inhibited electrically-evoked contractions (pEC50 8.63) that was sensitive to both Mu and NOP antagonists. DeNo was antinociceptive in rats. CONCLUSION: Collectively these data validate the strategy used to create a novel bivalent Mu-NOP peptide agonist by combining dermorphin (Mu) and N/OFQ (NOP). This molecule behaves essentially as the parent compounds in vitro. In the antonocicoeptive assays employed in this study DeNo displays only weak antinociceptive properties. PMID- 27272045 TI - Cost-effectiveness of pharmacogenetic-guided dosing of warfarin in the United Kingdom and Sweden. AB - We aimed to assess the cost-effectiveness of pharmacogenetic-guided dosing of warfarin in patients with atrial fibrillation (AF) in the United Kingdom and Sweden. Data from EU-PACT, a randomized controlled trial in newly diagnosed AF patients, were used to model the incremental costs per quality-adjusted life-year (QALY) gained by pharmacogenetic-guided warfarin dosing versus standard treatment over a lifetime horizon. Incremental lifetime costs were L26 and 382 Swedish kronor (SEK) and incremental QALYs were 0.0039 and 0.0015 in the United Kingdom and Sweden, respectively. The corresponding incremental cost-effectiveness ratios (ICERs) were L6 702 and 253 848 SEK per QALY gained. The ICER was below the willingness-to-pay threshold of L20 000 per QALY gained in 93% of the simulations in the United Kingdom and below 500 000 SEK in 67% of the simulations in Sweden. Our data suggest that pharmacogenetic-guided dosing of warfarin is a cost effective strategy to improve outcomes of patients with AF treated with warfarin in the United Kingdom and in Sweden. PMID- 27272044 TI - High frequency of CYP2D6 ultrarapid metabolizers in Spain: controversy about their misclassification in worldwide population studies. AB - A high frequency (7-10%) of CYP2D6 ultrarapid metabolizers estimated from the genotype (gUMs) has been claimed to exist among Spaniards and Southern Europeans. However, methodological aspects such as the inclusion of individuals carrying non active multiplied alleles as gUMs may have led to an overestimation. Thus, this study aimed to analyze the gUM frequency (considering only those carrying more than two active genes) in 805 Spanish healthy volunteers studied for CYP2D6*2, *3, *4, *5, *6, *10, *17, *35, *41, and multiplications. Second, all worldwide studies reporting gUM frequencies were reviewed in order to evaluate potential misclassifications. The gUM frequency in this Spanish population was 5.34%, but increased to 8.3% if all individuals with CYP2D6 multiplications were classified as gUMs without considering the activity of the multiplied alleles. Moreover, among all reviewed worldwide studies only 55.6% precisely determined whether the multiplied alleles were active. Present results suggest that the evaluation of CYP2D6 ultrarapid metabolism should be standarized, and that the frequency of gUMs should be reconsidered in Spaniards and globally. PMID- 27272047 TI - Penile Length and Testicular Volume in Newborns. AB - OBJECTIVES: To measure Penile length (PL) and Testicular volume (TV) in newborn boys for assessing genital abnormalities. METHODS: In a tertiary care setting, measurements of PL and TV were recorded from 480 babies born on alternate days except the weekend, at 24 to 72 h of life by one investigator with the same set of instruments. The penis was stretched to the point of increased resistance and the distance from the tip of the glans penis to the pubic ramus was measured as the stretched PL. Testicular volume was measured by a Prader orchidometer. Improvised beads made of plasticine were used for recording volumes <1 ml. RESULTS: In the study cohort, 365 (76.04 %) were term babies. The mean PL was 34 +/- 4.7 mm for the whole cohort while the corresponding value for mean TV was 0.6 +/- 0.2 ml. The gestation age-wise percentile charts of PL and TV have been generated. There was modest positive correlation between PL and TV. Positive correlation was also observed between PL and TV and birth weight, body length, and head, chest and arm circumference. Both PL and TV showed statistically significant increase with gestational age. By the index data, the cut-off for suspecting abnormal penile length should be <24.5 or >45.5 mm for term babies. CONCLUSIONS: The normative values generated can serve as reference standard in the diagnosis of penile length abnormalities in Indian babies and in clarifying issues of ambiguous genitalia and maldevelopment of male external genitalia. PMID- 27272048 TI - Diagnostic Value of Intestinal Fatty-Acid-Binding Protein in Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis. AB - The present study was undertaken to evaluate the performance of intestinal fatty acid-binding protein (i-FABP) in the diagnosis of newborn necrotizing enterocolitis (NEC) and prediction of surgical NEC. A comprehensive literature search was performed in PubMed and EMBASE to identify potential relevant studies. QUADAS-2 tool was used to assess the quality of the included studies. The sensitivity, specificity and other measurements of accuracy of i-FABP were pooled. Summary receiver operating characteristic curves (SROC) and area under the curve (AUC) were used to summarize overall diagnostic performance. After screening 150 titles and abstracts, followed by 32 full-text publications, 14 studies were included. The sample size, sensitivity, specificity, diagnostic odds ratio (DOR) and AUC were: plasma i-FABP 217, 0.64(95% CI 0.53 to 0.74), 0.91(95% CI 0.84 to 0.95), 14.22 (95%CI 6.42 to 31.52) and 0.84; urinary i-FABP 211, 0.64(95% CI 0.53 to 0.74), 0.73(95% CI 0.64 to 0.80), 6.35 (95%CI 3.17 to 12.72) and 0.81; urinary i-FABP/Cr 165, 0.78(95% CI 0.65 to 0.88), 0.75(95% CI 0.65 to 0.82), 6.35 (95%CI 3.17 to 12.72) and 0.81; plasma i-FABP for surgical NEC 45, 0.71(95% CI 0.51 to 0.87), 0.76(95% CI 0.50 to 0.93), 7.58 (95%CI 0.87 to 65.82) and 0.80. Plasma i-FABP is a promising biomarker in the diagnosis of NEC with high specificity and DOR; but its usefulness is limited because of medium sensitivity. The urinary i-FABP and urinary i-FABP/Cr add little value in the diagnosis. The findings were somewhat limited by the quality and small size of some of the studies included. PMID- 27272046 TI - Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes. AB - This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis. The statistical analysis was adjusted by age, gender, AP dosage, AP combinations and concomitant treatments as covariates. Four SNPs in different genes (DRD2, SLC18A2, HTR2A and GRIK3) contributed significantly to the risk of EPS after correction for multiple testing (P<1 * 10(-4)). These findings support the involvement of dopamine, serotonin and glutamate pathways in AP-induced EPS. PMID- 27272049 TI - Healthcare Costs to Poor Families: An Agonising Burden. PMID- 27272050 TI - Pre- and Postnatal Diagnosis of 5q35.1 and 8p23.1 Deletion in Congenital Heart Disease. PMID- 27272051 TI - Reply to the comment on: "Efficiency of bimaxillary advancement surgery in increasing the volume of the upper airways: a systematic review of observational studies and meta-analysis". PMID- 27272053 TI - LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain. AB - LAMP5 is member of the LAMP family of membrane proteins. In contrast to the canonical members of this protein family, LAMP1 and LAMP2, which show widespread expression in many tissues, LAMP 5 is brain specific in mice. In C. elegans, the LAMP5 ortholog UNC-46 has been suggested to act a trafficking chaperone, essential for the correct targeting of the nematode vesicular GABA-transporter UNC-47. We show here that in the mouse brain LAMP5 is expressed in subpopulations of GABAergic forebrain neurons in the striato-nigral system and the olfactory bulb. The protein was present at synaptic terminals, overlapping with the mammalian vesicular GABA-transporter VGAT. In LAMP5-deficient mice localization of the transporter was unaffected arguing against a conserved role in VGAT trafficking. Electrophysiological analyses in mutants showed alterations in short term synaptic plasticity suggesting that LAMP5 is involved in controlling the dynamics of evoked GABAergic transmission. At the behavioral level, LAMP5 mutant mice showed decreased anxiety and deficits in olfactory discrimination. Altogether, this work implicates LAMP5 function in GABAergic neurotransmission in defined neuronal subpopulations. PMID- 27272052 TI - Whole-brain changes in white matter microstructure after radiotherapy for nasopharyngeal carcinoma: a diffusion tensor imaging study. AB - Radiation-induced local white matter (WM) damage has been observed by diffusion tensor imaging (DTI) within a priori-defined regions of interest following radiotherapy (RT) for nasopharyngeal carcinoma (NPC). In this study, we aimed to detect WM changes throughout the brain of NPC patients by DTI. Tract-based spatial statistics (TBSS) was used to analyze DTI data from 81 NPC patients. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified across the whole brain in separate groups: pre-RT, and <6, 6-12, and >12 months post-RT. We found that fractional anisotropy values were significantly lower in the right frontal, parietal, and occipital WM <6 months post-RT compared with pre-RT and remained significantly lower in the right frontal and parietal WM at >12 months. MD values were significantly higher in the right occipital, bilateral temporal, right occipital-temporal junction, left parietal, left centrum semiovale, and left frontal-parietal junction WM <6 months post-RT and remained higher in the right occipital WM at >12 months. This study suggests that changes in white matter microstructure following RT for NPC were widespread, complex, and dynamic. Diffusion tensor imaging with TBSS analysis allows for early non-invasive detection of RT-induced WM damage. PMID- 27272054 TI - Effects of rapid maxillary expansion on facial soft tissues : Deviation analysis on three-dimensional images. AB - OBJECTIVE: Changes in soft tissue in various morphological regions of the face immediately after rapid maxillary expansion (RME) were examined using three dimensional (3D) deviation analyses. PATIENTS AND METHODS: A total of 50 patients were included in the study; 25 patients (11 female and 14 male) presented with a unilateral or bilateral posterior crossbite malocclusion requiring RME. In addition, 25 patients (13 female and 12 male) were included as a control group. The mean ages of the study group and control group were 9.8 years (range 8.1-12.6 years) and 9.6 years (range 8.3-12.2 years), respectively. The 3D stereophotogrammetric images acquired immediately before the appliance was cemented and after expansion had been completed in the treatment group were compared using Rapidform software. The 3D deviation analyses were made for the complete face and in the upper and lower face, upper and lower lips and nose regions. The amount of negative and positive deviations and the mean deviations were examined on the facial meshes for the 95th percentiles. RESULTS: Immediately after RME, the mean absolute deviation over the complete face was 0.54 +/- 0.16 mm. The mean change for the upper face was 0.42 +/- 0.17 mm (mean positive deviation: 0.37 +/- 0.17 mm; mean negative deviation: -0.48 +/- 0.18 mm). The mean absolute deviation was 0.62 +/- 0.28 mm in the upper lip and 0.60 +/- 0.34 mm in the lower lip. In the nose area, the absolute deviation was 0.41 +/- 0.21 mm (mean positive deviation: 0.39 +/- 0.16 mm; mean negative deviation: -0.43 +/- 0.26 mm). CONCLUSIONS: Changes in facial soft tissues in the upper face, lower face, nasal soft tissues, and lower and upper lip regions were observed after RME. PMID- 27272055 TI - Orthodontic mini-implant stability at different insertion depths : Sensitivity of three stability measurement methods. AB - OBJECTIVES: The purpose of this work was to evaluate the influence of insertion depth on the stability of orthodontic mini-implants. Sensitivity of three different methods to measure implant stability based on differences in insertion depth were determined. METHODS: A total of 82 mini-implants (2 * 9 mm) were inserted into pelvic bone of Swabian Hall pigs. Each implant was inserted stepwise to depths of 4, 5, 6, 7, and 8 mm. At each of these depths, three different methods were used to measure implant stability, including maximum insertion torque (MIT), resonance frequency analysis (RFA), and Periotest((r)). Differences between the recorded values were statistically analyzed and the methods tested for correlations. RESULTS: Almost linear changes from each insertion depth were measured with the values of RFA [implant stability quotient (ISQ) values range from 1-100], which increased from 6.95 +/- 2.85 ISQ at 4 mm to 34.63 +/- 5.51 ISQ at 8 mm, and with those of Periotest((r)) [periotest values (PTV) range from -8 to 50], which decreased from 13.24 +/- 4.03 PTV to -2.89 +/- 1.87 PTV. Both methods were found to record highly significant (p < 0.0001) changes for each additional millimeter of insertion depth. The MIT increased significantly (p < 0.0001) from 153.67 +/- 69.32 Nmm to 261 +/- 103.73 Nmm between 4 and 5 mm of insertion depth but no further significant changes were observed as the implants were driven deeper. The RFA and Periotest((r)) values were highly correlated (r = -0.907). CONCLUSIONS: Mini-implant stability varies significantly with insertion depth. The RFA and the Periotest((r)) yielded a linear relationship between stability and insertion depth. MIT does not appear to be an adequate method to determine implant stability based on insertion depth. PMID- 27272057 TI - [Application for Inpatient Psychosomatic Rehabilitation: Frequency, Quality, and Approval Rates]. AB - BACKGROUND: There has been a steady increase in psychiatric primary diagnoses in medical rehabilitation services carried out by the statutory pension insurance (DRV). To date, no data are available regarding frequency, quality, and approval rates of applications for psychosomatic rehabilitation. Pension insurance physicians reviewing the application require sufficient information on rehabilitation-related needs, motivation, abilities, and prognosis of an insured person. Medical reports accompanying application for rehabilitation are often provided by a family physician. Psychiatric disorders are often misdiagnosed by general practitioners. METHOD: In a 2-week period, all decisions made by pension insurance physicians evaluating applications for rehabilitation were recorded. For each incoming application, the following data were documented: psychiatric and somatic primary diagnosis; availability of medical reports; information on prior treatment/therapy; request for further information; decision made by the physician. RESULTS: 1,366 applications (with 81% first-time applications) were included in the analysis. 16.2% of all applications were from insurants with psychiatric primary diagnoses. 44.0% of these applications included a medical report from the family physician only. The proportion of rejected applications (34.7%) and undecided applications (27.2%) was higher in the group of applicants with psychiatric primary diagnosis vs. somatic primary diagnosis (19.6% rejected; 12.7% undecided; chi2=79.8(4), p=0.001). Applications from patients with psychiatric primary diagnosis that lacked a medical report from a psychiatrist/psychotherapist were more likely to be rejected (45.3 vs. 32.3%) or to remain undecided (28.0 vs. 18.3%; chi2=10.2(2), p=0.006). In contrast, among applicants with a history of psychiatric/psychotherapeutic treatment, there was a higher proportion of undecided applications accompanied by a medical report from the family physician (35.7 vs. 18.2%). CONCLUSION: It might be useful to have medical reports generally provided by medical specialists. This may help both to increase the informative value of applications for psychosomatic rehabilitation and enable quicker decisions and better diagnosis. PMID- 27272058 TI - [There is no Need to Reinvent the Wheel - Requirements for a Successful Project Transfer]. AB - Although the transfer of an existing project can be a resource-efficient form of implementation of successful interventions, project transfers are rarely carried out in practice. The aim of this article is to pool the experience of 3 projects about the transfer of their prevention approaches to other municipalities and regions, as well as to make recommendations for future trans-regional transfer processes in the field of disease prevention and health promotion. To achieve this, documentation sheets were used and interviews were conducted with team members of the transfer projects. The results show that the ability to adapt intervention to context is an essential condition of successful implementation. In addition, there has to be a need for the intervention in the transfer region and a benefit to the participant organizations as well as to the team members. Furthermore, constructive and personal communication and cooperation between the participants of the original and the transferred project are required for successful transfer. PMID- 27272059 TI - [Art Therapists in Health Care]. AB - The members of the Bundesarbeitsgemeinschaft Kunstlerische Therapien (BAG KT - "Working Committee of Art Therapies of the Federal Republic of Germany") decided to carry out an analysis of the occupational group of art therapists, in the form of an online inquiry. For this purpose, a questionnaire covering all fields of art therapies was developed, recording socio-demographic and qualification data, data of different fields of activity, patient characteristics, institutional conditions and setting as well as data on reimbursement. 2303 evaluable data sets are available. Here, the main focus is on art therapists in the health care sector according to SGB (N=2134). 83% of them are female, 56% work in the field of emergency medicine and curative treatment, followed by rehabilitation and youth welfare. In all sectors, specialization in music and art therapy predominates. 57% of the therapists have a special graduate degree in art therapy methods, 83% have a graduate degree. 42% have a license to work as an alternative non-medical practitioner. Nearly all of them use methods of quality management. The results highlight the implementation of art therapies in health care. PMID- 27272056 TI - Differential treatment effects of two anchorage systems for rapid maxillary expansion: a retrospective cephalometric study. AB - OBJECTIVES: The purpose of this study was to compare cephalometric changes resulting from treatment with two appliances for rapid maxillary expansion: (1) a strictly tooth-borne appliance and (2) a combined tooth- and bone-borne appliance. PATIENTS AND METHODS: Pre- and posttreatment lateral cephalograms of 100 patients were analyzed by cephalometry. Of these patients, 50 were treated with strictly tooth-borne and another 50 with combined tooth- and bone-borne appliances. Mean pretreatment age was 13.04 +/- 4.82 years, and mean treatment duration was 7.12 +/- 2.37 months. To identify any implications for clinical therapy, additional subgroups were formed based on the pretreatment cephalometric findings for skeletal Class I (0 degrees < ANB <= 4 degrees ) or Class III (ANB <=0 degrees ). Paired t-tests were used for intragroup and analysis of variance (ANOVA) for intergroup comparisons. Results were considered statistically significant at p <= 0.05. RESULTS: Both appliance types resulted in significant cephalometric changes in the maxilla and mandible. Compared to the strictly tooth borne appliances, the combined tooth- and bone-borne appliances were found to cause more pronounced advancement of the maxilla (SNA angle) notably among the Class III patients. CONCLUSIONS: Hybrid (combined tooth- and bone-borne) appliances for rapid maxillary expansion might be preferable in the treatment of skeletal Class III patients, since they possibly exert a more pronounced skeletal effect on the sagittal position of the maxilla. PMID- 27272060 TI - [Public Health as an Applied, Multidisciplinary Subject: Is Research-Based Learning the Answer to Challenges in Learning and Teaching?] AB - Public health education aims at enabling students to deal with complex health related challenges using appropriate methods based on sound theoretical understanding. Virtually all health-related problems in science and practice require the involvement of different disciplines. However, the necessary interdisciplinarity is only partly reflected in the curricula of public health courses. Also theories, methods, health topics, and their application are often taught side-by-side and not together. For students, it can become an insurmountable challenge to integrate the different disciplines ("horizontal integration") and theories, methods, health topics, and their application ("vertical integration"). This situation is specific for education in public health but is representative for other interdisciplinary fields as well. Several approaches are available to achieve the horizontal integration of different disciplines and vertical integration of theories, methods, health topics, and their application. A curriculum that is structured by topics, rather than disciplines might be more successful in integrating different disciplines. Vertical integration can be achieved by research-based learning. Research-based learning places a student-led research project at the centre of teaching. Students choose a topic and a research question, raise their own questions for theories and methods and will hopefully cross the seeming chasm between science and practice. Challenges of research-based learning are enhanced demands on students, teachers and curriculum design. PMID- 27272061 TI - Monodispersed lysozyme-functionalized bioactive glass nanoparticles with antibacterial and anticancer activities. AB - In this study, highly monodispersed spherical bioactive glass nanoparticles (BGS) with a particle size of 408 +/- 36 nm were synthesized using a modified Stober method. The BGS was then functionalized with lysozyme (LY) via a simple electrostatic interaction routine under selected conditions. The LY functionalized BGS (LY-BGS) exhibited monodispersity, spherical morphology and homogeneity in size. The incorporated content of LY could be tailored conveniently by adjusting the initial concentration of the LY precursor for functionalization. Hydroxyapatite (HA) formed on the LY-BGS after soaking in simulated body fluid (SBF) for 7 d, but the formation was retarded compared to the non-functionalized BGS. The LY-BGS showed antibacterial activity towards Gram positive B. subtilis and >90% of the bacteria was killed within 24 h after culture with the LY-BGS at a concentration of 1 mg ml(-1). The LY-BGS also showed cytotoxicity towards the human hepatocellular carcinoma (HepG2) cell line. In addition, the relative cytotoxicity increased with an increase in the concentration of the LY-BGS in contact with the cells. As a comparison, the LY BGS exhibited reduced or no cytotoxicity towards human umbilical vein endothelial cells (HUVECs) at the same concentration with respect to the HepG2 groups. Notably, the relative cell viability of HepG2 was 45.9% after exposure to the LY BGS at a concentration of 10 MUg ml(-1) for 24 h, while no decrease in relative viability for the HUVECs was observed under the same conditions. This cytotoxicity window between cancerous cells and healthy cells could be expected for cancer treatment. Furthermore, the antibacterial properties and the bioactivity of LY-BGS make it a promising material for biomedical applications, particularly in the treatment of bone defects caused by tumors. PMID- 27272062 TI - Cerebral radiofrequency exposures during adolescence: Impact on astrocytes and brain functions in healthy and pathologic rat models. AB - The widespread use of mobile phones by adolescents raises concerns about possible health effects of radiofrequency electromagnetic fields (RF EMF 900 MHz) on the immature brain. Neuro-development is a period of particular sensitivity to repeated environmental challenges such as pro-inflammatory insults. Here, we used rats to assess whether astrocyte reactivity, perception, and emotionality were affected by RF EMF exposures during adolescence. We also investigated if adolescent brains were more sensitive to RF EMF exposures after neurodevelopmental inflammation. To do so, we either performed 80 MUg/kg intra peritoneal injections of lipopolysaccharides during gestation or 1.25 MUg/h intra cerebro-ventricular infusions during adolescence. From postnatal day (P)32 to 62, rats were subjected to 45 min RF EMF exposures to the brain (specific absorption rates: 0, 1.5, or 6 W/kg, 5 days/week). From P56, they were tested for perception of novelty, anxiety-like behaviors, and emotional memory. To assess astrocytic reactivity, Glial Fibrillary Acidic Protein was measured at P64. Our results did not show any neurobiological impairment in healthy and vulnerable RF EMF-exposed rats compared to their sham-exposed controls. These data did not support the hypothesis of a specific cerebral sensitivity to RF EMF of adolescents, even after a neurodevelopmental inflammation. Bioelectromagnetics. 37:338-350, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272064 TI - Prevalence, incidence, and remission rates of urinary incontinence in women attended in gynecological practice. AB - AIMS: To assess the prevalence of urinary incontinence (UI) in a cohort of women attended in primary care gynecological and estimate the incidence and remission rates of UI symptoms at 1 year. METHODS: We performed a multicenter prospective cohort study of women attending eight primary care gynecological practices. Consecutive women attended for gynecological issues different from UI were invited to participate in the study by answering the International Consultation on Incontinence questionnaire-Short Form (ICIQ-UI-SF). Patients receiving treatment for UI, during pregnant, and postpartum were excluded. All women with UI symptoms (ICIQ-UI-SF > 0) wishing treatment were studied and treated following routine clinical practice. All women were invited to answer the same questionnaire by phone 1 year after inclusion. RESULTS: A total of 2,840 women answered the questionnaire; 1,188 (41.8%) had UI symptoms (ICIQ-UI-SF > 0). Accordingly, nearly half (44.9%) had mild UI symptoms. Treatment was requested by only 551/1,188 incontinent women (46.38%), being related to the severity of UI. At 1 year, 2,443 patients/2,840 (86.0%) were found and again responded to the ICIQ-UI-SF. At 1 year the incidence of UI was 5.3% (77 new cases of UI out of 1,652 with the initial ICIQ-UI-SF = 0) while the remission rate of UI among untreated women was 27.9% (144 with ICIQ-UI-SF = 0). CONCLUSIONS: Almost one half of women attended in primary care general gynecology practices have UI symptoms, with less than 50% requesting treatment. In these women, UI is a dynamic process with an incidence of 5.3% and a remission rate of 27.9% at 1 year. Neurourol. Urodynam. 36:1081-1085, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27272065 TI - A Rare Case of Pott's Disease (Spinal Tuberculosis) Mimicking Metastatic Disease in the Southern Region of Denmark. AB - BACKGROUND: Pott's disease (PD) or spinal tuberculosis is a rare condition which accounts for less than 1% of total tuberculosis (TB) cases. The incidence of PD has recently increased in Europe and the United States, mainly due to immigration; however, it is still a rare diagnosis in Scandinavian countries, and if overlooked it might lead to significant neurologic complications. CASE REPORT: A 78-year-old woman, originally from Eastern Europe, presented to the emergency department with a complaint of nausea, vomiting, weight loss, and severe back pain. On admission she was febrile and had leukocytosis and increased C-reactive protein. Initial spinal x-ray was performed and revealed osteolytic changes in the vertebral body of T11 and T12. Magnetic resonance imaging (MRI) of the spine illustrated spondylitis of T10, T11, and T12, with multiple paravertebral and epidural abscesses, which was suggestive of PD. Polymerase chain reaction (PCR) of the patient's gastric fluid was positive for Mycobacterium tuberculosis (MT). Based on MRI and PCR findings, standard treatment for TB was initiated. Results of the spine biopsy and culture showed colonies of MT and confirmed the diagnosis afterwards. Due to the instability of the spine and severe and continuous pain, spine-stabilizing surgery was performed. Her TB was cured after nine months of treatment. CONCLUSIONS: PD is an important differential diagnosis of malignancy that should be diagnosed instantly. History of exposure to TB and classic radiologic finding can help make the diagnosis. PMID- 27272066 TI - Publically Misfitting: Extreme Weight and the Everyday Production and Reinforcement of Felt Stigma. AB - Living with extreme weight in the United States is associated with discrimination and self-stigma, creating structural exclusions, embodied stress, and undermining health and wellbeing. Here we combine ethnographic interviews and surveys from those with experiences of living with extreme weight to better explain how this vulnerability is created and reinforced by public cues, both physical (e.g., seatbelts) and social (the reactions of strangers). "Misfitting" is a major theme in interviews, as is the need to plan and scan constantly while navigating too small public spaces. The most distressing events combine physical misfitting with unsympathetic reactions from strangers. Sensitivity to stigmatizing public cues reduces with weight loss, but does not disappear. This study explains one basic mechanism that underlies the creation of felt stigma related to weight even after weight loss: the lack of accommodation for size and the lack of empathy from others that characterize modern urban spaces. PMID- 27272067 TI - NPS: Medical Consequences Associated with Their Intake. AB - Over the last decade, the 'traditional' drug scene has been supplemented - but not replaced - by the emergence of a range of novel psychoactive substances (NPS), which are either newly created or existing drugs, including medications, now being used in novel ways. By the end of 2014, in excess of 500 NPS had been reported by a large number of countries in the world. Most recent data show, however, that synthetic cathinones, synthetic cannabinoids, and psychedelics/phenethylamines account for the largest number of NPS.The present chapter aims at providing an overview of the clinical and pharmacological issues relating to these most popular NPS categories. Given the vast range of medical and psychopathological issues associated with the molecules here described, it is crucial for health professionals to be aware of the effects and toxicity of NPS. A general overview of the acute management of NPS adverse events is provided as well, although further studies are required to identify a range of evidence based, index molecule-focused, treatment strategies. The rapid pace of change in the NPS online market constitutes a major challenge to the provision of current and reliable scientific knowledge on these substances. PMID- 27272068 TI - Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells. AB - Pharmacological assays carried out in transfected cells have been very useful for describing the mechanism of action of cathinone new psychoactive substances (NPS). These in vitro characterizations provide fast and reliable information on psychoactive substances soon after they emerge for recreational use. Well investigated comparator compounds, such as methamphetamine, 3,4 methylenedioxymethamphetamine, cocaine, and lysergic acid diethylamide, should always be included in the characterization to enhance the translation of the in vitro data into clinically useful information. We classified cathinone NPS according to their pharmacology at monoamine transporters and receptors. Cathinone NPS are monoamine uptake inhibitors and most induce transporter mediated monoamine efflux with weak to no activity at pre- or postsynaptic receptors. Cathinones with a nitrogen-containing pyrrolidine ring emerged as NPS that are extremely potent transporter inhibitors but not monoamine releasers. Cathinones exhibit clinically relevant differences in relative potencies at serotonin vs. dopamine transporters. Additionally, cathinone NPS have more dopaminergic vs. serotonergic properties compared with their non-beta-keto amphetamine analogs, suggesting more stimulant and reinforcing properties. In conclusion, in vitro pharmacological assays in heterologous expression systems help to predict the psychoactive and toxicological effects of NPS. PMID- 27272069 TI - Brain Structures Implicated in Inflammation-Associated Depression. AB - Systemic inflammation rapidly impairs mood, motivation, and cognition inducing a stereotyped cluster of symptoms collectively known as "sickness behaviors." When inflammation is severe or chronic, these behavioral changes can appear indistinguishable from major depressive disorder (MDD). Human and rodent neuroimaging combined with experimental inflammatory challenges has clarified the neural circuitry associated with many of the key features of inflammation-induced sickness behavior, and in so doing revealed often-remarkable commonalities with circuit abnormalities observed in MDD. This review aims to provide the first synthesis of this work illustrating areas of convergence and divergence with the MDD literature as well as highlighting areas for future study. PMID- 27272071 TI - Overstating Conclusions from Population-Based Data: Be Careful What You Wish For! PMID- 27272072 TI - Hormonal Contraceptives and Acne: A Retrospective Analysis of 2147 Patients. AB - INTRODUCTION: Although hormonal contraceptives may help acne or worsen it, there is limited evidence on the effects of many commonly prescribed agents. The present study evaluates patient-reported effect on acne from 2147 patients who were utilizing a hormonal contraceptive at the time of their initial consultation for acne.
METHODS: At the time of initial consultation for acne, each of 2147 consecutive patients using hormonal contraception provided her assessment of how her contraceptive had affected her acne. The Kruskal-Wallis test and logistic regression analysis were used to compare patient-reported outcomes by contraceptive type.
RESULTS: Depot injections, subdermal implants, and hormonal intrauterine devices worsened acne on average, and were inferior to the vaginal ring and combined oral contraceptives (COCs; P ≤ .001 for all pairwise comparisons), which improved acne on average. Within COC categories, a hierarchy emerged based on the progestin component, where drospirenone (most helpful) > norgestimate and desogestrel > levonorgestrel and norethindrone (P ≤ .035 for all pairwise comparisons). The presence of triphasic progestin dosage in COCs had a positive effect (P = .005), while variation in estrogen dose did not have a significant effect (P = .880).
CONCLUSIONS: Different hormonal contraceptives have significantly varied effects on acne, including among types of COC.

J Drugs Dermatol. 2016;15(6):670-674. PMID- 27272073 TI - Topical Treatment With an Agent Disruptive to P. acnes Biofilm Provides Positive Therapeutic Response: Results of a Randomized Clinical Trial. AB - The traditional disease model of acne has been one of follicular plugging due to 'sticky epithelial cells' associated with increased sebum production with deep follicular anaerobic conditions favoring P. acnes- generated inflammation. P. acnes biofilms have been found more frequently in patients with acne than controls. Biofilms are genetically coded to create adhesion to the pilosebaceous unit followed by production of a mucopolysaccharide coating capable of binding to lipid surfaces. Traditional therapies for acne have involved mixtures of oral and topical antibiotics admixed with topical keratolytics and retinoids, which are aimed at traditional bacterial reduction as well as downregulating the inflammatory cascade. These approaches are limited by side effect and compliance/tolerability issues. As the P. acnes biofilm may, in fact, be the instigator of this process, we studied the use of a topical agent designed to reduce the P. acnes biofilm to see if reducing the biofilm would be therapeutically efficacious. We present data of a proprietary topical non-prescription agent with a novel pharmaco mechanism designed to attack the biofilm produced by P. acnes. Our data shows a decrease of inflammatory lesions by 44% and non-inflammatory lesions by 32% after 12 weeks and also provided for a meaningful improvement in the quality of life of the patients in the study. These improvements were achieved with a product that was not associated with burning, chafing, irritation, or erythema, which can be seen with topical treatments. It is apparent from this study that by addressing the biofilm which protects the P. acnes bacteria through the use of the Acne Gel, the incidence of acne symptoms can be greatly reduced, while having no negative impacts on the patients' skin (ClinicalTrials.gov registry number NCT02404285).

J Drugs Dermatol. 2016;15(6):677-683. PMID- 27272074 TI - Colloidal Oatmeal (Avena Sativa) Improves Skin Barrier Through Multi Therapy Activity. AB - Oats (Avena sativa) are a centuries-old topical treatment for a variety of skin barrier conditions, including dry skin, skin rashes, and eczema; however, few studies have investigated the actual mechanism of action for the skin barrier strengthening activity of colloidal oatmeal. Four extracts of colloidal oatmeal were prepared with various solvents and tested in vitro for skin barrier related gene expression and activity. Extracts of colloidal oatmeal were found to induce the expression of genes related to epidermal differentiation, tight junctions and lipid regulation in skin, and provide pH-buffering capacity. Colloidal oatmeal boosted the expression of multiple target genes related to skin barrier, and resulted in recovery of barrier damage in an in vitro model of atopic dermatitis. In addition, an investigator-blinded study was performed with 50 healthy female subjects who exhibited bilateral moderate to severe dry skin on their lower legs. Subjects were treated with a colloidal oatmeal skin protectant lotion. Clinically, the colloidal oatmeal lotion showed significant clinical improvements in skin dryness, moisturization, and barrier. Taken together, these results demonstrate that colloidal oatmeal can provide clinically effective benefits for dry and compromised skin by strengthening skin barrier.

J Drugs Dermatol. 2016;15(6):684-690. PMID- 27272070 TI - Human Drug Discrimination: Elucidating the Neuropharmacology of Commonly Abused Illicit Drugs. AB - Drug-discrimination procedures empirically evaluate the control that internal drug states have over behavior. They provide a highly selective method to investigate the neuropharmacological underpinnings of the interoceptive effects of drugs in vivo. As a result, drug discrimination has been one of the most widely used assays in the field of behavioral pharmacology. Drug-discrimination procedures have been adapted for use with humans and are conceptually similar to preclinical drug-discrimination techniques in that a behavior is differentially reinforced contingent on the presence or absence of a specific interoceptive drug stimulus. This chapter provides a basic overview of human drug-discrimination procedures and reviews the extant literature concerning the use of these procedures to elucidate the underlying neuropharmacological mechanisms of commonly abused illicit drugs (i.e., stimulants, opioids, and cannabis) in humans. This chapter is not intended to review every available study that used drug-discrimination procedures in humans. Instead, when possible, exemplary studies that used a stimulant, opioid, or Delta9-tetrahydrocannabinol (the primary psychoactive constituent of cannabis) to assess the discriminative stimulus effects of drugs in humans are reviewed for illustrative purposes. We conclude by commenting on the current state and future of human drug discrimination research. PMID- 27272075 TI - New Atrophic Acne Scar Classification: Reliability of Assessments Based on Size, Shape, and Number. AB - BACKGROUND: Post-acne atrophic scarring is a major concern for which standardized outcome measures are needed. Traditionally, this type of scar has been classified based on shape; but survey of practicing dermatologists has shown that atrophic scar morphology has not been well enough defined to allow good agreement in clinical classification. Reliance on clinical assessment is still needed at the current time, since objective tools are not yet available in routine practice.
OBJECTIVES: Evaluate classification for atrophic acne scars by shape, size, and facial location and establish reliability in assessments.
METHODS: We conducted a non-interventional study with dermatologists performing live clinical assessments of atrophic acne scars. To objectively compare identification of lesions, individual lesions were marked on a high-resolution photo of the patient that was displayed on a computer during the clinical evaluation. The Jacob clinical classification system was used to define three primary shapes of scars 1) icepick, 2) boxcar, and 3) rolling. To determine agreement for classification by size, independent technicians assessed the investigators' markings on digital images. Identical localization of scars was denoted if the maximal distance between their centers was ≤ 60 pixels (approximately 3 mm). Raters assessed scars on the same patients twice (morning/afternoon). Aggregate models of rater assessments were created and analyzed for agreement.
RESULTS: Raters counted a mean scar count per subject ranging from 15.75 to 40.25 scars. Approximately 50% of scars were identified by all raters and ~75% of scars were identified by at least 2 of 3 raters (weak agreement, Kappa pairwise agreement 0.30). Agreement between consecutive counts was moderate, with Kappa index ranging from 0.26 to 0.47 (after exclusion of one outlier investigator who had significantly higher counts than all others). Shape classifications of icepick, boxcar, and rolling differed significantly between raters and even for same raters at consecutive sessions (P<.001 and P=0.4, respectively). Analysis showed only 65% of scars were identical in both sessions. We also found that there is a threshold of detection in terms of size, with poor agreement among investigators for very small scars (<2 mm). The repeatability of identification of scars ≥ 2.0 mm was acceptable, and we found that increasing scar size was positively correlated with agreement. Reliability was improved when only scars >2 mm were included. For smaller scars (<2 mm), inter-rater reliability was poor.
CONCLUSIONS: While intuitively it makes sense that describing scar morphology could guide treatment, we have shown that shape-based evaluations are subjective and do not readily yield strong agreement. Until there is a more objective way to evaluate morphology that is readily available to practicing clinicians, we propose that size should be considered a primary characteristic for scar classification systems. We further suggest classification of <2 mm, 2-4 mm, and >4 mm based on how the size would likely affect diagnostic and therapeutic choices. Finally, we recommend that scars <2 mm not be included in a clinical classification but should be evaluated by an objective method that may be refined in the future.

J Drugs Dermatol. 2016;15(6):693-702. PMID- 27272076 TI - Bimatoprost 0.03% Solution for the Treatment of Nonfacial Vitiligo. AB - BACKGROUND: Topical prostaglandin E2 has shown efficacy in patients with localized, stable vitiligo. Bimatoprost is a synthetic prostamide (prostaglandin-ethanolamides) F2a analog. Bimatoprost 0.03% ophthalmic solution showed efficacy in the treatment of vitiligo in one small study.
OBJECTIVE: To assess the efficacy and safety of bimatoprost 0.03% alone and in combination with a topical steroid (mometasone) compared with mometasone alone in patients with nonsegmental vitiligo on nonfacial areas in a proof-of-concept study.
METHODS: This randomized, double-blind, controlled study was conducted over a 20-week treatment period. Patients were randomized to 1 of 3 treatment groups: bimatoprost monotherapy (n=11), bimatoprost plus mometasone (n=10), and mometasone plus placebo (n=11). The primary outcome was global response at week 20, based on an investigator's assessment of improvement score of at least 5 (at least 50%-75% improvement from baseline) on an 8-point scale (0=worse; 7=cleared). Other outcomes included global response at other visits, response by anatomic site, change from baseline lesion severity (overall and by site), and safety.
RESULTS: Because of a lack of response observed for the primary end point, a post hoc analysis with a less stringent definition of response (score of ≥4 [25%-50% improvement]) was conducted. In this analysis, 46% of the bimatoprost plus mometasone group responded overall compared with 18% in the bimatoprost monotherapy group, and no patients in the mometasone plus placebo group. Greater response rates were observed in both bimatoprost groups compared with the mometasone plus placebo group starting at week 12. There were no differences among groups in signs and symptoms of irritation.
CONCLUSIONS: Bimatoprost alone or with mometasone provided greater repigmentation than treatment with mometasone alone. Larger studies that also assess facial lesions are warranted.

J Drugs Dermatol. 2016;15(6):703-710. PMID- 27272077 TI - Utilization of Optical Coherence Tomography in the Evaluation of Cherry Hemangiomas. AB - Cherry hemangiomas are common vascular proliferative lesions that can be concerning from a cosmetic perspective. Laser therapy is often used to eradicate cherry hemangiomas, but some lesions require multiple treatments or do not resolve at all. The suboptimal response to laser treatment may be due to limitations in penetration depth by vascular lasers such as the pulsed dye laser. Optical coherence tomography is a low-energy, light-based imaging device that can evaluate the depth and extent of vascular lesions such as cherry hemangiomas by allowing visualization of tissue structure and blood vessel architecture, which cannot be appreciated by clinical or dermatoscopic examination alone. We present optical coherence tomography images of a cherry hemangioma to demonstrate the precision and resolution of this imaging modality. Optical coherence tomography provides valuable information that has the potential to predict response to laser therapy without unnecessary attempts. Future prospective studies will determine its value for this purpose.

J Drugs Dermatol. 2016;15(6):713-714. PMID- 27272078 TI - Mycophenolate Mofetil in Severe Atopic Dermatitis: A Review. AB - Atopic Dermatitis (AD) is a chronic inflammatory skin disease that is a significant cause of morbidity, quality-of-life impairment and health-care costs. Although many patients can be treated satisfactorily with topical medications and phototherapy, a smaller subset requires more aggressive systemic therapies. Multiple studies have shown promise for the use of mycophenolate mofetil (MMF) to treat refractory AD. This report summarizes the evidence for use of MMF in the treatment of recalcitrant AD for both children and adults. Familiarity with these studies on the benefits and risks of MMF will enable the clinician and patient to select the most appropriate therapy.

J Drugs Dermatol. 2016;15(6):715-718. PMID- 27272079 TI - Two Randomized, Double-Blind, Split-Face Studies to Compare the Irritation Potential of Two Topical Acne Fixed Combinations Over a 21-Day Treatment Period. AB - Topical therapy of acne vulgaris (acne) is very common, however cutaneous tolerability can influence patient adherence, and concerns about skin irritation have lead to a number of comparative split-face studies. Advances in formulation technology have provided new fixed combinations with lower concentrations of potentially irritating ingredients without compromising efficacy. These developments now afford the opportunity to formulate fixed combinations with higher concentrations of active ingredients that may provide the greater efficacy needed in more severe disease with good tolerability.
Here, we compare the tolerability of two such developments, clindamycin-BP 3.75% gel and adapalene 0.3%-BP 2.5% gel, in healthy volunteers with no apparent facial redness or dryness over 21-days, using a split-face methodology.
Clindamycin-BP 3.75% gel was more tolerable than adapalene 0.3%-BP 2.5% gel over the duration of the two studies, with statistically significant differences in cumulative change from baseline starting as early as day 4 (stinging), day 5 (erythema, dryness, and scaling), day 6 (burning), and day 8 (itching); and in composite irritation index (stinging, erythema, dryness, scaling, burning, and itching) from day 4. Transepidermal water loss was less with clindamycin-BP 3.75% gel (statistically significant from day 8). Adverse events were twice as common with adapalene 0.3% BP 2.5% gel.
These data suggest that clindamycin-BP 3.75% gel is likely to be better tolerated than adapalene 0.3%-BP 2.5% gel in moderate-to-severe acne.

J Drugs Dermatol. 2016;15(6):721-726. PMID- 27272080 TI - Photodynamic Therapy With Topical 5% 5-Aminolevulinic Acid for the Treatment of Truncal Acne in Asian Patients. AB - BACKGROUND: Photodynamic therapy (PDT) using topical application of aminolevulinic acid (ALA) is an effective treatment for acne vulgaris. However, there is no clear consensus on the treatment regime in Asians.
AIM: To determine the efficacy, safety and tolerability of 5% ALA PDT in the treatment of truncal acne in Asians.
METHODS: Patients with truncal acne were treated with 5%-ALA under occlusion for 3 hours. All were subsequently treated with a red light source at wavelength 630 nm and an irradiance of 38mW/cm2 giving a total dose of 37 J/cm2. The numbers of acne lesions were recorded at baseline and regular intervals after treatment together with any adverse effects.
RESULTS: Fifteen patients were recruited. Overall, there was a 64.2% reduction in the inflammatory lesions count and a 24.3% reduction in the non-inflammatory lesions count at the end of the 12 weeks follow-up. Both mean lesions counts were significantly lower than baseline at all follow-up time points with paired t tests (all P values <0.05). Pain was well tolerated among our patients.
CONCLUSION: A single treatment session of 5%-ALA PDT was effective for the treatment of truncal acne with little side effects and acceptable in our Asian patients.

J Drugs Dermatol. 2016;15(6):727-732. PMID- 27272081 TI - Antimycotic Studies of Miconazole Nanovesicles Formulation vs Candida Strain. AB - OBJECTIVE: Present research work was aimed at formulation and evaluation of antifungal activity of miconazole nitrate (MN) vesicles vs C. albicans spp.
METHODS: Miconazole loaded vesicles were prepared by coacervation phase separation technique using nonionic surfactants and stabilizers. The antimycological activity of vesicles was performed using agar disc diffusion technique.
RESULTS: The miconazole nitrate lipid vesicles F5A and F5B showed maximum activity with higher zones of inhibition ie, 13.95+1.54 mm and 13.64+0.65 mm, respectively, after 3 days (For all comparisons, P<.05 was considered significant).
CONCLUSION: The findings of this study suggest antifungal potential of a novel preparation of miconazole nitrate vesicles vs Candida albicans in the treatment of mycoses in dermatological practice.

J Drugs Dermatol. 2016;15(6):734-737. PMID- 27272082 TI - The Effect of a Combination of Recombinant EGF Cosmetic Serum and a Crosslinked Hyaluronic Acid Serum as Compared to a Fibroblast-Conditioned Media Serum on the Appearance of Aging Skin. AB - Anti-aging cosmeceutical efficacy is hampered by lack of active ingredient purity and lack of dosing standardization. These are two important key factors necessary to insure consistent, reproducible, and documentable skin effects. Without this type of standardization, it is not possible for cosmeceutical science to advance. Growth factors are interesting cosmeceutical ingredients with established cosmetic skin effects that can now be standardized due to the recent ability to manufacture recombinant epidermal growth factor. The concomitant use of a recombinant epidermal growth factor with a filler grade hyaluronic acid (EGF/RHA) was studied over 12 weeks in 60 females with mild to moderate photoaging as compared to a currently marketed spent fibroblast growth media and moisturizer (TNS). Investigator, noninvasive, and subject assessments were collected at baseline and weeks 2, 4, 8, and 12. The blinded investigator noted a statistically significant preference for the EGF/RHA at week 2 in terms of smoothness (P =0.003) and firmness (P =0.003). This improvement continued into weeks 4 and 8 with continued superior EGF/RHA results in fine lines (P =0.002), radiance (P =0.014), and overall appearance (P =0.027) by week 12. Transepidermal water loss was reduced for the EGF/RHA over the TNS at week 12 (P =0.005). The subjects gave high ratings to both study products. This research demonstrates the utility of recombinant growth factors, when combined with hyaluronic acid hydration, in improving skin cosmetic attributes. The ability to manufacture consistent pure recombinant growth factors lays the foundation for improved scientific study of this category of cosmeceutical actives.

J Drugs Dermatol. 2016;15(6):738-741. PMID- 27272083 TI - Efficacy and Safety of Naftifine HCl Cream 2% in the Treatment of Pediatric Subjects With Tinea Corporis. AB - BACKGROUND: Tinea corporis is fungal infection of body surfaces other than the feet, groin, scalp, or beard. Naftifine hydrochloride is a topical antifungal of the allylamine class used to treat tinea corporis, displaying fungicidal activity and clinically significant anti-bacterial and anti-inflammatory effects.
OBJECTIVE: To evaluate the efficacy and safety of two-weeks once daily application of naftifine cream 2% in the treatment of tinea corporis among pediatric subjects.
METHODS: At baseline, 231 subjects were randomly assigned 1:1 to naftifine cream 2% (n=116) and vehicle (n=115). Treatment effect consisting of mycologic determination (KOH and dermatophyte cultures) and scoring of clinical symptom severity was evaluated at baseline, week 2 (end of treatment) and week 3. Efficacy was analyzed in 181 subjects (n=88, naftifine; n=93, vehicle) with a positive baseline dermatophyte culture and KOH for whom week 3 assessments were available. Safety was evaluated by adverse events (AE) and laboratory values in 231 subjects (n=116, naftifine; n=115, vehicle).
RESULTS: Children with tinea corporis treated with naftifine cream 2% demonstrated significantly greater improvements from baseline over vehicle for mycological cure (P<0.0001) and treatment effectiveness (P=0.003) as early as 2 weeks (end of treatment). Response rates continued to increase post-treatment and were the highest 1-week after completion of the therapy (P=0.003 for complete cure; and P<0.001 for mycological cure and treatment effectiveness). Treatment related adverse events were minimal.
CONCLUSIONS: Treatment with naftifine cream 2% applied once daily for two weeks was well-tolerated and was effective in treating tinea corporis in children. Further improvement was observed 1-week after treatment completion for all key outcome measures (complete cure, mycological cure, treatment effectiveness, clinical cure, and clinical success) and clinical signs and symptoms (erythema, induration, and pruritus).

J Drugs Dermatol. 2016;15(6):743-748. PMID- 27272084 TI - A Double-Blind, 12-Week Study to Evaluate the Antiaging Efficacy of a Cream Containing the NFkappaB Inhibitor 4-Hexyl-1, 3-Phenylenediol and Ascorbic Acid-2 Glucoside in Adult Females. AB - The 5 main physical manifestations of aged skin are wrinkles, uneven tone, brown spots, loss of elasticity, and dryness. One mechanism resulting in these physical manifestations is increased activity of the nuclear factor kappa B (NFkappaB) protein. This 12-week, double-blind, placebo-controlled, randomized split-face study compared the antiaging effect and safety of a face cream containing 4-Hexyl 1, 3-phenylenediol, an NFkappaB inhibitor, and ascorbic acid-2 glucoside versus placebo in adult females aged 45-70 years old. Subjects (n=42) applied active treatment or placebo to the same half face twice daily at home for 12 weeks. Clinical evaluation was carried out by a dermatologist. Subjects carried out similar self-grading assessments. Colorimetric measurements analyzed skin color, and biomechanical skin properties were evaluated. Clinical grading showed that most wrinkle parameters were significantly improved after 8 weeks of active treatment compared with baseline and placebo (P≤.05), with improvements maintained after 12 weeks. Only Marionette wrinkles did not show a significant improvement. Brown spots (color intensity/number), overall photodamage, and most complexion parameters improved significantly after 8 and 12 weeks compared with baseline and placebo (P≤.05). Self-grading yielded similar results compared with baseline. Self-grading did not demonstrate improvements with active treatment versus placebo, except for skin firmness at 8 and 12 weeks (P≤.05). A significant difference was seen with active treatment compared with placebo in all colorimetric parameters (L*, b*, and ITA degrees ) after 8 weeks, and in spot coloration (b*) after 12 weeks (P<.05). Improvements in skin elasticity were not significantly different between treatments. Overall tolerability of active treatment was judged as good. In conclusion, a cream containing 4-Hexyl-1, 3-phenylenediol and ascorbic acid-2 glucoside improves the clinical appearance of aged skin, validating the potential use of NFkappaB inhibition as a novel, effective method of topical antiaging.

J Drugs Dermatol. 2016;15(6):750-758. PMID- 27272085 TI - Injectable Poly-L-Lactic Acid: Understanding Its Use in the Current Era. AB - A survey of Sculptra(r) Aesthetic injectors was conducted to understand how the product is being currently reconstituted and injected. Questions were asked of injectors to understand their reasons for choice and volume of diluent(s), additions, and time for the reconstitution process. These results are discussed in the context of the past history of the product over the last decade, with a focus on adverse events such as papules and nodules.

J Drugs Dermatol. 2016;15(6):759-762. PMID- 27272086 TI - Paradoxical Erythema Reaction of Long-term Topical Brimonidine Gel for the Treatment of Facial Erythema of Rosacea. AB - In 2013 brimonidine tartrate gel 0.33% (Mirvaso Gel, Galderma Laboratories, LP, Fort Worth, TX) was approved by the US Food and Drug Administration for the treatment of facial erythema of rosacea. It is the first and only drug on the market to address the hallmark redness of this chronic, inflammatory disease. Commonly reported adverse events include erythema/flushing worse than at baseline, most often occurring with the first application. We report a unique case of facial erythema of rosacea that responded to brimonidine gel with effective blanching for two years until the patient developed a paradoxical erythema reaction. This is an adverse reaction physicians should be aware of with continued prescription of brimonidine gel for their rosacea patients.

J Drugs Dermatol. 2016;15(6):763-765. PMID- 27272087 TI - Vitiligo of the Face in a Patient Treated With Vemurafenib for Metastatic Melanoma. AB - Vemurafenib is a potent and selective BRAF inhibitor, which is effective on patients with BRAF V600E mutated late-stage melanoma. Common and less common adverse skin reactions include photosensitivity, maculo-papular exanthema, hand foot skin reactions, hyperkeratotic follicular rash, pruritus, benign verrucous papillomas, plantar hyperkeratosis, keratoacanthomas, squamous cell carcinomas, infections, and melanoma. To our knowledge, vitiligo has been reported in 2 cases only. This paper reports the case of a 63-year-old man with metastatic melanoma, who developed sudden facial depigmentation after 4 weeks of treatment with vemurafenib 960 mg twice daily. Features consistent with vitiligo were evident at clinical and ultraviolet light examination, as well as at in vivo reflectance confocal microscopy. The latter examination showed lack of normal brightly refractile papillary rings at the dermo-epidermal junction in lesional skin, as well as decreased brightness and half-rings with "scalloped border-like" features in adjacent non-lesional skin. Vitiligo is an adverse reaction to be expected in patients treated with vemurafenib and whether its occurrence may be associated with a positive outcome, as suggested by previous investigations, is still a matter of debate.

J Drugs Dermatol. 2016;15(6):766-768. PMID- 27272088 TI - A Sequential Approach to the Treatment of Severe Papulopustular Rosacea Not Responding to Traditional Treatment. AB - We report the case of a German female patient presenting with papulopustular rosacea (PPR) with a high count of facial inflammatory lesions and severe erythema who had not responded well to treatment with traditional therapies for a decade. In this patient, a sequential therapy consisting of oral modified-release doxycycline 40 mg (initially as monotherapy, then in combination with topical metronidazole), followed by topical ivermectin 10 mg/g was both rapidly active and effective. Following reduction of the inflammation with modified-release doxycycline 40 mg upfront and the disease becoming moderate in severity, the dose of this agent could be reduced and combination therapy with metronidazole 7.5 mg/g lotion started to continue decreasing inflammatory lesions count and erythema severity, before treatment with the recently approved agent ivermectin 10 mg/g was implemented to provide almost complete clearance. This sequential treatment was effective in reducing both the number of papules and pustules and the severity of erythema, with a good safety profile. In addition, a large improvement was documented in the patient's DLQI score, contributing to her overall wellbeing.

J Drugs Dermatol. 2016;15(6):769-771. PMID- 27272089 TI - Failure of Anakinra in a Case of Severe Hidradenitis Suppurativa. AB - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful, inflammatory disorder of hair follicles and manifests with several cutaneous findings, including double comedones, papules, cysts, nodules, draining abscesses, and sinus tracts. It is associated with tremendous morbidity and decreased quality of life. Treatment of HS is challenging. Recently, there have been mixed reports regarding the efficacy of anakinra, an interleukin 1 receptor antagonist, in the management of HS.
CASE: A 55-year-old African American male with a several year history of severe HS, recalcitrant to multiple prior treatments, was treated with a 12 week course of anakinra 100 mg subcutaneously daily. After 3 months of therapy, minimal change was observed, and the patient strongly preferred to cease therapy due to lack of improvement and pain associated with daily injections.
CONCLUSION: Our case of severe HS proved refractory to anakinra. Tolerance of this therapy may be a limiting factor for some patients due to necessity for daily injections.

J Drugs Dermatol. 2016;15(6):772-774. PMID- 27272090 TI - Pragmatic and Profound Benefits of Acyclovir Buccal Adhesive Tablets. AB - The clinician has many options, both systemic and topical, for the management of oro-labial herpes simplex infections due to HSV-1. A recent addition to this armamentarium is Acyclovir 50 mg Buccal Adhesive Tablets (ABT 50mg). While this agent demonstrates the typical modest reduction in time to healing of any given episode of recurrent oro-labial HSV 1, it also was found in pivotal studies to alter the course of this troublesome viral disease. Several case reports are presented which dramatically illustrate that ABT 50mg can reduce the overall number of overt outbreaks and increase the time interval between outbreaks in patients with historical evidence of frequent episodes. This therapeutic intervention is thus: simple, safe, efficacious and cost-effective, even in patients who experience numerous (and therefore disconcerting) oro-labial outbreaks.

J Drugs Dermatol. 2016;15(6):775-777. PMID- 27272091 TI - Effect of GT-Peptide 10 and Triethyl Citrate on P. acnes Biofilm Formation, Viability, and Dispersion. AB - BACKGROUND: P. acnes biofilms are emerging topics in acne vulgaris pathogenesis and may be responsible for antibiotic tolerance.
OBJECTIVE: To investigate the efficacy of GT peptide 10 either alone or in combination with triethyl citrate (TEC) in in vitro model of P. acnes biofilm.
METHODS: Six-day-old P. acnes biofilms were treated with various concentrations of these substances and biofilm dispersion and cell viability were monitored.
RESULTS: A 24-hour exposure of preformed biofilms to a combination of GT peptide 10/TEC led to killing of up to 92% of bacterial cells inside the biofilm. Neither the single substance nor the combination of both substances affected the biofilm integrity or resulted in biofilm dispersal.
CONCLUSIONS: A combination of GT peptide 10/TEC shows antibacterial effects in in vitro model of P. acnes biofilm.

J Drugs Dermatol. 2016;15(6):778-781. PMID- 27272092 TI - Resident Rounds: Part III - Case Report: Betel Quid Induced Irritant Contact Dermatitis of the Hand. AB - Betel quid is a drug used in Far East Asia, India, and the South Pacific. The habit of betel quid chewing is widely reported to cause oral cancer and tooth and gum disease. However, skin disease due to betel quid use is underreported. We report a case of irritant contact dermatitis to betel quid components in a 35 year-old male betel quid user who presented for evaluation of a persistent rash on his fingertips. PMID- 27272093 TI - The Revised Nutrition Facts Label: A Step Forward and More Room for Improvement. PMID- 27272094 TI - Values as determinant of meaning among patients with psychiatric disorders in the perspective of recovery. AB - Recovery is a personal process of growth that involves hope, self-identity, meaning in life and responsibility. Determinants of meaning have not been explored among populations of patients with persistent psychiatric conditions. However, an evidence-based approach aiming at assessing such determinants should provide some insight into the psychotherapeutic aspects of recovery. We tested a model hypothesizing that some symptoms and social parameters of patients are related to values, and secondarily to meaning in life, and in turn that meaning is associated with various parameters, such as depressiveness and self-esteem. We assessed 176 patients with schizophrenia, anorexia, borderline personality disorder and bipolar disorder. Overall, our hypotheses proved correct: firstly, characteristics such as depression, hopelessness, self-esteem and the number of relationships influenced values; secondly, the presence and an enactment of values were associated with meaning, and thirdly, meaning was associated with some symptoms and social characteristics. This model was confirmed in the four psychiatric populations under study. These results support the relevance of addressing values and meaning in the recovery-oriented care of patients with persistent psychiatric disorders, in addition to other psychosocial interventions which are more systematically considered in this area. PMID- 27272097 TI - Real time and online dynamic speckle assessment of growing bacteria using the method of motion history image. AB - This paper reports the application of the motion history image (MHI) method for biospeckle processing of a bacterial growth. The method avoids the complexity as well as the large computation in sequence-matching-based methods and detects whether the speckle structure has changed or not. Encouraging experimental results on the real-time evolution of the growing bacteria during 12 h demonstrate the effectiveness of the proposed method. The MHI presented an online result without loss of resolution and definition. In turn, the MHI also presented the ability to provide a close answer to the traditional offline method of generalized differences. PMID- 27272095 TI - Repeatability and reproducibility of optic nerve head perfusion measurements using optical coherence tomography angiography. AB - Optical coherence tomography angiography (OCTA) has increasingly become a clinically useful technique in ophthalmic imaging. We evaluate the repeatability and reproducibility of blood perfusion in the optic nerve head (ONH) measured using optical microangiography (OMAG)-based OCTA. Ten eyes from 10 healthy volunteers are recruited and scanned three times with a 68-kHz Cirrus HD-OCT 5000 based OMAG prototype system (Carl Zeiss Meditec Inc., Dublin, California) centered at the ONH involving two separate visits within six weeks. Vascular images are generated with OMAG processing by detecting the differences in OCT signals between consecutive B-scans acquired at the same retina location. ONH perfusion is quantified as flux, vessel area density, and normalized flux within the ONH for the prelaminar, lamina cribrosa, and the full ONH. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) are used to evaluate intravisit and intervisit repeatability, and interobserver reproducibility. ONH perfusion measurements show high repeatability [CV<=3.7% (intravisit) and <=5.2% (intervisit)] and interobserver reproducibility (ICC<=0.966) in all three layers by three metrics. OCTA provides a noninvasive method to visualize and quantify ONH perfusion in human eyes with excellent repeatability and reproducibility, which may add additional insight into ONH perfusion in clinical practice. PMID- 27272096 TI - Grueneisen relaxation photoacoustic microscopy in vivo. AB - Grueneisen relaxation photoacoustic microscopy (GR-PAM) can achieve optically defined axial resolution, but it has been limited to ex vivo demonstrations so far. Here, we present the first in vivo image of a mouse brain acquired with GR PAM. To induce the GR effect, an intensity-modulated continuous-wave laser was employed to heat absorbing objects. In phantom experiments, an axial resolution of 12.5 MUm was achieved, which is sixfold better than the value achieved by conventional optical-resolution PAM. This axial-resolution improvement was further demonstrated by imaging a mouse brain in vivo, where significantly narrower axial profiles of blood vessels were observed. The in vivo demonstration of GR-PAM shows the potential of this modality for label-free and high-resolution anatomical and functional imaging of biological tissues. PMID- 27272098 TI - The relationship between breastfeeding self-efficacy and LATCH scores and affecting factors. AB - AIMS AND OBJECTIVES: This study investigates the relationship between breastfeeding self-efficacy and LATCH scores and affecting factors in Turkish mothers. BACKGROUND: The benefits of breastfeeding for newborns and mothers are well documented. Type of birth, maternal and neonatal complications; lack of support from healthcare professionals during breastfeeding, hospital routines, time and duration of mother-newborn attachment; and insufficiency of husband and family support are the most significant factors affecting breastfeeding initiation and mothers' breastfeeding self-efficacy in early postpartum period. Therefore, it is important to determine how all these factors affect breastfeeding. DESIGN: This was a cross-sectional, descriptive study. METHODS: The sample of the study consisted of 303 postpartum women who were recruited at the obstetrics clinic of maternity hospital in one of the three largest city of Turkey. The data were obtained using Personal Identification Form, Breastfeeding Self-Efficacy Scale-Short Form and LATCH Breastfeeding Assessment Tool to determine breastfeeding success. The mean, standard deviation, frequency, percentages, correlation analysis and Kruskal-Wallis variance analysis were used in data collection. RESULTS: The main finding of the study was a weak positive correlation between average LATCH scores and average Breastfeeding Self-Efficacy Scale-Short Form scores of women in the postpartum period. The women becoming pregnant four times or more got significantly higher average Breastfeeding Self Efficacy Scale-Short Form and average LATCH scores, and the women married for 11 years or longer and the mothers starting to breastfeed their babies within 30 minutes of their birth got significantly higher average LATCH scores. CONCLUSIONS: The results of the present research affirm the beneficial role of high self-efficacy in successful breastfeeding. RELEVANCE TO CLINICAL PRACTICE: It is of great importance that midwives and obstetric nurses routinely evaluate breastfeeding self-efficacy and the capability of breastfeeding for early detection of problems related to breastfeeding. PMID- 27272099 TI - Mechanical Isolation of Highly Stable Antimonene under Ambient Conditions. AB - Antimonene fabricated by mechanical exfoliation is highly stable under atmospheric conditions over periods of months and even when immersed in water. Density functional theory confirms the experiments and predicts an electronic gap of ~1 eV. These results highlight the use of antimonene for optoelectronics applications. PMID- 27272100 TI - Peri- and postoperative cognitive and consecutive functional problems of elderly patients. AB - PURPOSE OF REVIEW: From an elderly patient's perspective, acute and chronic cognitive disturbances are among the most harmful complications that can occur following surgery. For elderly patients, these complications often mean the end of an independent life. This article focuses on this serious aspect, which is increasingly prevalent in our aging society. Cognitive disturbances are associated with severe outcome impairments and increased mortality. This article aims to provide a current overview regarding the diagnosis, pathophysiology, prevention, and treatment of this severe social problem. RECENT FINDINGS: The current knowledge of risk factors, diagnosis, prevention, and treatment of postoperative delirium and postoperative cognitive dysfunction should help to raise awareness and improve the outcome of delirious patients, particularly in the elderly population. SUMMARY: Especially in elderly patients, postoperative delirium constitutes a common, severe complication. Early diagnosis and supportive treatment are essential to improve outcome. To date, no pharmacological treatment strategy was effective, so that further research about the underlying pathophysiology and the development of treatment strategies are urgently required. PMID- 27272101 TI - Anabolic and anticatabolic agents in critical care. AB - PURPOSE OF REVIEW: A complex network of hormones and other effectors characterize the hypermetabolic response in critical illness; these mediators work together to induce numerous pathophysiologic alterations. Increased incidence of infection, multiorgan failure, long-term debilitation, delays in rehabilitation, and death result from an inability to meet the prohibitively elevated protein and energy requirements, which occur during illness and can persist for several years. Pharmacologic interventions have been successfully utilized to attenuate particular aspects of the hypermetabolic response; these modalities are a component of managing critically ill patients - including those patients with severe burns. Here, we review recent advances in pharmacologically attenuating the hypermetabolic and catabolic responses. RECENT FINDINGS: Propranolol, a nonspecific beta-adrenergic receptor antagonist, is one of the most widely used anticatabolic therapies. Oxandrolone, testosterone, and intensive insulin therapy represent anabolic pharmacological strategies. Promising therapies, such as metformin, glucagon-like peptide 1, peroxisome proliferator-activated receptor agonists, are currently being investigated. SUMMARY: Profound metabolic derangements occur in critically ill patients; this hypermetabolic response is a major contributor to adverse outcomes. Despite the pharmacological therapies currently available to counteract this devastating cascade, future studies are warranted to explore new multimodality agents that will counteract these effects while maintaining glycemic control and preventing unfavorable complications. PMID- 27272102 TI - Minimalistic Ditopic Ligands: An alpha-S,N-Donor-Substituted Alkyne as Effective Intermetallic Conjugation Linker. AB - The capability of donor-substituted alkynes to link different metal ions in a side-on carbon donor-chelate coordination mode is extended from the donor centers S and P to the second period element N. The complex [Tp'W(CO)2 {eta(2) -C2 (S)(NHBn)}] (Tp'=hydrido-tris(3,5-dimethylpyrazolyl)borate, Bn=benzyl) bearing a terminal sulfur atom and a secondary amine substituent is accessible by a metal template synthesis. Subsequent deprotonation allowed the formation of remarkably stable heterobimetallic complexes with the [(eta(5) -C5 H5 )Ru(PPh3 )] and the [Ir(ppy)2 ] moiety. Electrochemical and spectroscopic investigations (cyclic voltammetry, IR, UV/Vis, luminescence, EPR), as well as DFT calculations, and X ray structure determinations of the W-Ru complex in two oxidation states reveal a strong metal-metal coupling but also a limited delocalization of excited states. PMID- 27272103 TI - The Birmingham Urban Climate Laboratory-A high density, urban meteorological dataset, from 2012-2014. AB - There is a paucity of urban meteorological observations worldwide, hindering progress in understanding and mitigating urban meteorological hazards and extremes. High quality urban datasets are required to monitor the impacts of climatological events, whilst providing data for evaluation of numerical models. The Birmingham Urban Climate Laboratory was established as an exemplar network to meet this demand for urban canopy layer observations. It comprises of an array of 84 wireless air temperature sensors nested within a coarser array of 24 automatic weather stations, with observations available between June 2012 and December 2014. data routinely underwent quality control, follows the ISO 8601 naming format and benefits from extensive site metadata. The data have been used to investigate the structure of the urban heat island in Birmingham and its associated societal and infrastructural impacts. The network is now being repurposed into a testbed for the assessment of crowd-sourced and satellite data, but the original dataset is now available for further analysis, and an open invitation is extended for its academic use. PMID- 27272105 TI - Development of an effective therapy and objective assessment for children with birth injuries. AB - Sitting in a Huple, a patented hemisphere-like tool, permanently stimulates the vestibular system, thus improving the balancing ability of children with movement disorders. The Gezenguz Foundation for Children with Birth Injuries has been successfully applying this tool in therapy. By attaching x-Inertial Measurement Unit, a wireless three-dimensional orientation sensor, to the Huple, it can serve as an input peripheral for simple PC games. Children are thus motivated; they willingly perform balance training as well as participate in the game-like test. This improves the accuracy and reproducibility of the assessment. Knowing the actual state of the participants is an important element of feedback for the therapy. This paper describes in detail the development of the therapeutic and assessment method on the basis of the Huple: the definition of the movement pattern, the parameters characterizing the movement, and the algorithms used to rank children. Measurement series of 10 children with movement disorders validate the effectiveness of the game-like assessment. PMID- 27272104 TI - Genetics of aging bone. AB - With aging, the skeleton experiences a number of changes, which include reductions in mass and changes in matrix composition, leading to fragility and ultimately an increase of fracture risk. A number of aspects of bone physiology are controlled by genetic factors, including peak bone mass, bone shape, and composition; however, forward genetic studies in humans have largely concentrated on clinically available measures such as bone mineral density (BMD). Forward genetic studies in rodents have also heavily focused on BMD; however, investigations of direct measures of bone strength, size, and shape have also been conducted. Overwhelmingly, these studies of the genetics of bone strength have identified loci that modulate strength via influencing bone size, and may not impact the matrix material properties of bone. Many of the rodent forward genetic studies lacked sufficient mapping resolution for candidate gene identification; however, newer studies using genetic mapping populations such as Advanced Intercrosses and the Collaborative Cross appear to have overcome this issue and show promise for future studies. The majority of the genetic mapping studies conducted to date have focused on younger animals and thus an understanding of the genetic control of age-related bone loss represents a key gap in knowledge. PMID- 27272106 TI - Oncological Outcomes of Major Liver Resection Following Portal Vein Embolization: A Systematic Review and Meta-analysis. AB - BACKGROUND: Preoperative portal vein occlusion with either percutaneous portal vein embolization (PVE) or portal vein ligation is routinely used to induce liver hypertrophy prior to major liver resection in patients with hepatic malignancy. While this increases the future liver remnant, and hence the number of patients suitable for resection, recent evidence suggests that induction of liver hypertrophy preoperatively may promote tumor growth and increase recurrence rates. The aims of this current study were to evaluate the impact of PVE on hepatic recurrence rate and survival in patients with colorectal liver metastases (CRLM). METHODS: The MEDLINE, EMBASE and Web of Science databases were searched to identify studies assessing the oncological outcomes of patients undergoing major liver resection for CRLM following PVE. Studies comparing patients undergoing one-stage liver resection with or without preoperative PVE were included. The primary outcome was postoperative hepatic recurrence (PHR), while secondary outcomes were 3- and 5-year overall survival (OS). RESULTS: Of the 2131 studies identified, six non-randomized studies (n = 668) met the eligibility criteria, comparing outcomes of patients undergoing major liver resection with or without PVE (n = 182 and n = 486, respectively). No significant difference was observed in PHR (odds ratio [OR] 0.78; 95 % confidence interval [CI] 0.42-1.44), 3-year OS (OR 0.80; 95 % CI 0.56-1.14) or 5-year OS (OR 1.12; 95 % CI 0.40-3.11). CONCLUSIONS: PVE does not have any adverse effect on PHR or OS in patients undergoing major liver resection for CRLM. Further studies based on individual patient data are needed to provide definitive answers. PMID- 27272107 TI - Prognostic Impact of Palliative Primary Tumor Resection for Unresectable Stage 4 Colorectal Cancer: Using a Propensity Score Analysis. AB - BACKGROUND: The benefits that palliative resection of the primary tumor offers patients with unresectable stage 4 colorectal cancer, specifically with regard to overall survival, are controversial, and the issue is complicated by marked differences in patient backgrounds and characteristics. METHODS: The study enrolled 770 consecutive patients with unresectable stage 4 colorectal cancer referred to the divisions of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1997 to 2013. Of these patients, 429 (56 %) underwent palliative resection of the primary tumor, whereas 341 (44 %) did not. To lessen the effects of confounding factors between the groups, including age, year, severe symptoms, number of organs involved by metastases, primary tumor site, and carcinoembryonic antigen (CEA) value, propensity score analyses were used for regression adjustment, stratification, and matching, with overall survival as the primary end point. RESULTS: The regression adjustment including the propensity score as a linear predictor in the model showed that palliative resection was associated with a significantly improved overall survival (hazard ratio [HR] 0.60; 95 % confidence interval [CI] 0.50-0.71; p < 0.01)]. Stratification analysis showed that in all five strata, palliative resection was associated with better overall survival (HR 0.43-0.73). Similarly, the propensity score-matched cohort (267 matched pairs) yielded an HR of 0.58 (95 % CI 0.48-0.70; p < 0.01). CONCLUSIONS: The findings suggest that palliative resection of the primary tumor may be associated with improved overall survival. Further investigations such as prospective randomized trials are needed to confirm this result. PMID- 27272108 TI - Lord Walton of Detchant - obituary. PMID- 27272109 TI - Comment on 'Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses'. PMID- 27272110 TI - Progressive ataxia in a natalizumab-treated multiple sclerosis patient: the dark side of JC virus infection. PMID- 27272111 TI - Flaws in the development of the CHESS score. PMID- 27272112 TI - Authors' reply. PMID- 27272114 TI - SOD3 Ameliorates Abeta25-35-Induced Oxidative Damage in SH-SY5Y Cells by Inhibiting the Mitochondrial Pathway. AB - This study was designed to investigate the protective effects of extracellular superoxide dismutase (SOD3) against amyloid beta (Abeta25-35)-induced damage in human neuroblastoma SH-SY5Y cells and to elucidate the mechanisms responsible for this beneficial effect. SH-SY5Y cells overexpressing SOD3 were generated by adenoviral vector-mediated infection and Abeta25-35 was then added to the cell culture system to establish an in vitro model of oxidative stress. Cell viability, the generation of intracellular reactive oxygen species (ROS), the expression and activity of antioxidant enzymes, the levels of lipid peroxidation malondialdehyde (MDA), the expression of mitochondrial apoptosis-related genes and calcium images were examined. Following Abeta25-35 exposure, SOD3 overexpression promoted the survival of SH-SY5Y cells, decreased the production of ROS, decreased MDA and calcium levels, and decreased cytochrome c, caspase-3, caspase-9 and Bax gene expression. Furthermore, SOD3 overexpression increased the expression and activity of antioxidant enzyme genes and Bcl-2 expression. Together, our data demonstrate that SOD3 ameliorates Abeta25-35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial pathway. These data provide new insights into the functional actions of SOD3 on oxidative stress-induced cell damage. PMID- 27272115 TI - Brief Report: A Pilot Study of the Use of a Virtual Reality Headset in Autism Populations. AB - The application of virtual reality technologies (VRTs) for users with autism spectrum disorder (ASD) has been studied for decades. However, a gap remains in our understanding surrounding VRT head-mounted displays (HMDs). As newly designed HMDs have become commercially available (in this study the Oculus RiftTM) the need to investigate newer devices is immediate. This study explored willingness, acceptance, sense of presence and immersion of ASD participants. Results revealed that all 29 participants (mean age = 32; 33 % with IQ < 70) were willing to wear the HMD. The majority of the participants reported an enjoyable experience, high levels of 'presence', and were likely to use HMDs again. IQ was found to be independent of the willingness to use HMDs and related VRT immersion experience. PMID- 27272116 TI - Effect of yttrium-90 radioembolization on outcomes in Asian patients with early to advanced stage hepatocellular carcinoma. AB - AIM: The aim of this study was to investigate the effect of yttrium-90 radioembolization on the outcome of Asian patients with early to advanced stage hepatocellular carcinoma (HCC). METHODS: Sixty-two patients were screened and 50 patients (80.6%) were eligible. Response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST), and overall survival was estimated using the Kaplan-Meier method. RESULTS: The Barcelona Clinic Liver Cancer (BCLC) stage was A in 40% of patients, B in 24%, and C in 36%; 66% of patients had hepatitis B virus infections. According to RECIST criteria, partial responses occurred in 40% of patients, and stable disease was achieved in 46%. Tumor response was significantly associated with BCLC stage (P = 0.003). The median overall time to progression was 5.8 months (range, 0.9-46.1 months). Follow-up treatments after radioembolization were carried out in 31 patients due to remnant HCC (n = 18) or HCC progression (n = 13). The median overall survival was 40.9 months (95% confidence interval, 10.2-71.6 months). Treatment was tolerable except for one lung toxicity and two hepatic toxicities. CONCLUSION: Yttrium-90 radioembolization appears to be well tolerated and effective in Asian patients with BCLC stage A-C HCC. Follow-up treatments after radioembolization can be safely provided. PMID- 27272118 TI - Anticipating the Challenges of Zika Virus and the Incidence of Guillain-Barre Syndrome. PMID- 27272119 TI - FamPipe: An Automatic Analysis Pipeline for Analyzing Sequencing Data in Families for Disease Studies. AB - In disease studies, family-based designs have become an attractive approach to analyzing next-generation sequencing (NGS) data for the identification of rare mutations enriched in families. Substantial research effort has been devoted to developing pipelines for automating sequence alignment, variant calling, and annotation. However, fewer pipelines have been designed specifically for disease studies. Most of the current analysis pipelines for family-based disease studies using NGS data focus on a specific function, such as identifying variants with Mendelian inheritance or identifying shared chromosomal regions among affected family members. Consequently, some other useful family-based analysis tools, such as imputation, linkage, and association tools, have yet to be integrated and automated. We developed FamPipe, a comprehensive analysis pipeline, which includes several family-specific analysis modules, including the identification of shared chromosomal regions among affected family members, prioritizing variants assuming a disease model, imputation of untyped variants, and linkage and association tests. We used simulation studies to compare properties of some modules implemented in FamPipe, and based on the results, we provided suggestions for the selection of modules to achieve an optimal analysis strategy. The pipeline is under the GNU GPL License and can be downloaded for free at http://fampipe.sourceforge.net. PMID- 27272117 TI - Does bariatric surgery improve adipose tissue function? AB - Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. (c) 2016 World Obesity. PMID- 27272120 TI - Clinical predictors and microbiology of ventilator-associated pneumonia in the intensive care unit: a retrospective analysis in six Italian hospitals. AB - The purpose of this study was to assess the main clinical predictors and microbiological features of ventilator-associated pneumonia (VAP) in the Intensive Care Unit (ICU) environment. This work is a retrospective analysis over one year from September 2010 to September 2011. Patients' risk factors, causes of admission, comorbidities and respiratory specimens collected in six Italian ICUs were reviewed. Incidence and case fatality rate of VAP were evaluated. After stratification for VAP development, univariate and multivariate analyses were performed to assess the impact of patients' conditions on the onset of this infection. A total of 1,647 ICU patients (pts) were considered. Overall, 115 patients (6.9 %) experienced at least one episode of VAP. The incidence rate for VAP was 5.82/1,000 pts-days, with a case fatality rate of 44.3 %. Multivariate analysis showed that admission for neurological disorders (aIRR 4.12, CI 1.24 13.68, p = 0.02) and emergency referral to ICU from other hospitals (aIRR 2.11, CI 1.03-4.31, p = 0.04) were associated with higher risk of VAP, whereas a tendency to a higher risk of infection was detected for admission due to respiratory disease, cardiac disease, trauma and for having obesity or renal failure. A total of 372 microbiological isolates from respiratory specimens were collected in VAP patients. The most common species were Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, showing high resistance rates to carbapenems. Neurological disorders and emergency referral at the admission into the ICU are significantly associated with the onset of VAP. A high incidence of multi-drug resistant Gram- species was detected in the respiratory specimens. PMID- 27272121 TI - Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response. AB - Data on the effects of sustained virologic response (SVR) to hepatitis C virus (HCV) therapy on the outcome of extrahepatic complications are scarce. We conducted this study to assess the impact of SVR on the occurrence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of human immunodeficiency virus (HIV)-infected patients. We analyzed coinfected HIV/HCV patients in the Management of Standardized Evaluation of Retroviral HIV Infection (MASTER) cohort. Only event-free patients with a serum HCV-RNA determination at baseline were included. Patients were divided into four groups: INF-exposed with SVR; INF-exposed without SVR; spontaneous HCV clearance; untreated viremic patients. We estimated the incidence of extrahepatic complications and employed Kaplan-Meier curves and Cox regression to assess the association of SVR/INF strata adjusted for a series of confounders. Data from 1676 patients were analyzed (20.29 % started an INF-based regimen). Overall, the incidence of CKD, DM, CVD, and death was 5.32 [95 % confidence interval (CI) 3.99 6.98], 10.13 (95 % CI 8.20-12.37), 6.79 (95 % CI 5.26-8.65), and 13.49 (95 % CI 11.29-16.0) per 1000 person-years of follow-up, respectively. In the Cox model for treated patients, SVR was not associated with a lower risk of CKD, DM, CVD, and death compared to non-SVR. Cirrhosis was significantly associated with a higher risk of CKD [hazard ratio (HR) 2.13; 95 % CI 1.06-4.31], DM (HR 3.48; 95 % CI 2.18-5.57), and death (HR 6.18; 95 % CI 4.1-9.31), but not of CVD (HR 1.14; 95 % CI 0.57-2.3). There are still many unknowns regarding the impact of SVR on the occurrence of extrahepatic complications in coinfected HIV/HCV patients. Further investigations are needed in order to elucidate the role of SVR as an independent prognostic factor for extrahepatic events. PMID- 27272122 TI - Larva migrans syndrome caused by Toxocara and Ascaris roundworm infections in Japanese patients. AB - Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well. PMID- 27272123 TI - Time to Detection with BacT/Alert FA Plus Compared to BacT/Alert FA Blood Culture Media. AB - Rapid identification of the causative pathogen in patients with bacteremia allows adjustment of antibiotic therapy and improves patient outcomes. We compared in vitro and real-life time to detection (TTD) of two blood culture media, BacT/Alert FA (FA) and BacT/Alert FA Plus (FA Plus), for the nine most common species of bacterial pathogens recovered from blood samples. Experimental data from simulated cultures was compared with microbiology records of TTD for both culture media with growth of the species of interest in clinical blood cultures. In the experimental conditions, median TTD was 3.8 hours (23.9 %) shorter using FA Plus media. The magnitude of reduction differed between species. Similarly, in real life data, FA Plus had shorter TTD than FA media; however, the difference between culture media was smaller, and median TTD was only 1 hour (8.5 %) less. We found shorter TTD with BacT/Alert FA Plus culture media, both experimentally and in real-life conditions and unrelated to antibiotic neutralization, highlighting the importance of appropriate blood culture media selection. PMID- 27272124 TI - Blood biochemical and oxidant/antioxidant alterations following stanozolol treatment along with resistance training in rats. AB - This study was designed to determine the effects of anabolic steroid stanozolol (ST) in conjunction with 8 weeks of resistance training on some blood biochemical and oxidant/antioxidant profile in rats. Twenty-four male rats were divided into four groups of six each: group 1: sedentary + placebo (physiological saline), group 2: training + placebo, group 3: training + ST (2 mg kg-1 b.w.) and group 4: training + ST (5 mg kg-1 b.w.). Erythrocytic activity of glutathione peroxidase was increased significantly in group 4 as compared to control group. Plasma activities of alanine aminotransferase in groups 3 and 4 and also aspartate aminotransferase in group 4 showed significant increase relative to groups 1 and 2. Moreover, alkaline phosphatase and creatine kinase activities increased significantly in groups 3 and 4 in comparison with control group. Elevated values of uric acid were significant in group 4, but not in groups 2 and 3, as compared to control group. Values of other measured parameters did not have significant alterations among experimental groups. Present findings indicate that stanozolol treatment in combination with resistance training induces some side effects especially on liver and muscle as evidenced by alterations in plasma markers of tissue damage. PMID- 27272126 TI - Composition-dependent trap distributions in CdSe and InP quantum dots probed using photoluminescence blinking dynamics. AB - Although Group II-VI quantum dots (QDs) have attracted much attention due to their wide range of applications in QD-based devices, the presence of toxic ions in II-VI QDs raises environmental concerns. To fulfill the demands of nontoxic QDs, synthetic routes for III-V QDs have been developed. However, only a few comparative analyses on optical properties of III-V QDs have been performed. In this study, the composition-related energetic trap distributions have been explored by using three different types of core/multishell QDs: CdSe-CdS (CdSe/CdS/ZnS), InP-ZnSe (InP/ZnSe/ZnS), and InP-GaP (InP/GaP/ZnS). It was shown that CdSe-CdS QDs have much larger trap densities than InP-shell QDs at higher energy states (at least 1Eg (band gap energy) above the lowest conduction band edge) based on probability density plots and Auger ionization efficiencies which are determined by analyses of photoluminescence blinking dynamics. This result suggests that the composition of encapsulated QDs is closely associated with the charge trapping processes, and also provides an insight into the development of more environmentally friendly QD-based devices. PMID- 27272125 TI - Genome editing and the next generation of antiviral therapy. AB - Engineered endonucleases such as homing endonucleases (HEs), zinc finger nucleases (ZFNs), Tal-effector nucleases (TALENS) and the RNA-guided engineered nucleases (RGENs or CRISPR/Cas9) can target specific DNA sequences for cleavage, and are proving to be valuable tools for gene editing. Recently engineered endonucleases have shown great promise as therapeutics for the treatment of genetic disease and infectious pathogens. In this review, we discuss recent efforts to use the HE, ZFN, TALEN and CRISPR/Cas9 gene-editing platforms as antiviral therapeutics. We also discuss the obstacles facing gene-editing antiviral therapeutics as they are tested in animal models of disease and transition towards human application. PMID- 27272128 TI - What is optimal treatment for vertiginous migraine? PMID- 27272127 TI - Contribution of high-content imaging technologies to the development of anti infective drugs. AB - Originally developed to study fundamental aspects of cellular biology, high content imaging (HCI) was rapidly adapted to study host-pathogen interactions at the cellular level and adopted as a technology of choice to unravel disease biology. HCI platforms allow for the visualization and quantification of discrete phenotypes that cannot be captured using classical screening approaches. A key advantage of high-content screening technologies lies in the possibility to develop and interrogate physiologically significant, predictive ex vivo disease models that reproduce complex conditions relevant for infection. Here we review and discuss recent advances in HCI technologies and chemical biology approaches that are contributing to an increased understanding of the intricate host pathogen interrelationship on the cellular level, and which will foster the development of novel therapeutic approaches for the treatment of human bacterial and protozoan infections. (c) 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC. PMID- 27272129 TI - Reliability and validity of a self-administration version of DEMQOL-Proxy. AB - OBJECTIVE: This study aimed to investigate the reliability and validity of a self administered version of DEMQOL-Proxy, a disease-specific instrument that measures health-related quality of life in people with dementia. METHODS: The sample consisted of 173 informal carers of people with dementia, aged 29 to 89 years old. Carers were mostly female, White/White British and closely related to the patient. They completed DEMQOL-Proxy (self-administered), EQ-5D-3L (proxy reported about the person with dementia), EQ-5D-3L (self-reported about their own health) and the Zarit Burden Interview. Using well-established methods from classical test theory, we evaluated scale level acceptability, reliability and convergent, discriminant and known-groups validity of DEMQOL-Proxy. RESULTS: DEMQOL-Proxy (self-administered) showed high acceptability (3.5% missing data and 0% scores at floor or ceiling), high internal consistency reliability (alpha = 0.93) and good convergent and discriminant validity. Amongst others, we found a moderately high correlation with EQ-5D-3L proxy reported (r = 0.52) and low to essentially zero correlations with EQ-5D-3L self-reported (r = 0.20) and carer and patient background variables (r <= 0.20). As predicted, DEMQOL-Proxy (self administered) showed a modest correlation with DEMQOL (r = 0.32). Known-groups differences on health-related quality of life (comparing people with versus people without cognitive impairment) were of moderate effect size (d = 0.38) and in the expected direction. CONCLUSIONS: DEMQOL-Proxy (self-administered) has comparable acceptability, reliability and validity with DEMQOL-Proxy (interviewer administered). DEMQOL-Proxy (self-administered) can be used in a wider variety of contexts than its interviewer-administered version, including routine use in busy clinics. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27272131 TI - Tai Chi for chronic obstructive pulmonary disease (COPD). AB - BACKGROUND: Tai Chi, a systematic callisthenic exercise first developed in ancient China, involves a series of slow and rhythmic circular motions. It emphasises use of 'mind' or concentration to control breathing and circular body motions to facilitate flow of internal energy (i.e. 'qi') within the body. Normal flow of 'qi' is believed to be essential to sustain body homeostasis, ultimately leading to longevity. The effect of Tai Chi on balance and muscle strength in the elderly population has been reported; however, the effect of Tai Chi on dyspnoea, exercise capacity, pulmonary function and psychosocial status among people with chronic obstructive pulmonary disease (COPD) remains unclear. OBJECTIVES: * To explore the effectiveness of Tai Chi in reducing dyspnoea and improving exercise capacity in people with COPD.* To determine the influence of Tai Chi on physiological and psychosocial functions among people with COPD. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials (which included the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED) and PsycINFO); handsearched respiratory journals and meeting abstracts; and searched Chinese medical databases including Wanfang Data, Chinese Medical Current Contents (CMCC), Chinese Biomedical Database (CBM), China Journal Net (CJN) and China Medical Academic Conference (CMAC), from inception to September 2015. We checked the reference lists of all primary studies and review articles for relevant additional references. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing Tai Chi (Tai Chi alone or Tai Chi in addition to another intervention) versus control (usual care or another intervention identical to that used in the Tai Chi group) in people with COPD. Two independent review authors screened and selected studies. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted data from included studies and assessed risk of bias on the basis of suggested criteria listed in the Cochrane Handbook for Systematic Reviews of Interventions. We extracted post-programme data and entered them into RevMan software (version 5.3) for data synthesis and analysis. MAIN RESULTS: We included a total of 984 participants from 12 studies (23 references) in this analysis. We included only those involved in Tai Chi and the control group (i.e. 811 participants) in the final analysis. Study sample size ranged from 10 to 206, and mean age ranged from 61 to 74 years. Programmes lasted for six weeks to one year. All included studies were RCTs; three studies used allocation concealment, six reported blinded outcome assessors and three studies adopted an intention-to-treat approach to statistical analysis. No adverse events were reported. Quality of evidence of the outcomes ranged from very low to moderate.Analysis was split into three comparisons: (1) Tai Chi versus usual care; (2) Tai Chi and breathing exercise versus breathing exercise alone; and (3) Tai Chi and exercise versus exercise alone.Comparison of Tai Chi versus usual care revealed that Tai Chi demonstrated a longer six-minute walk distance (mean difference (MD) 29.64 metres, 95% confidence interval (CI) 10.52 to 48.77 metres; participants = 318; I(2) = 59%) and better pulmonary function (i.e. forced expiratory volume in one second, MD 0.11 L, 95% CI 0.02 to 0.20 L; participants = 258; I(2) = 0%) in post-programme data. However, the effects of Tai Chi in reducing dyspnoea level and improving quality of life remain inconclusive. Data are currently insufficient for evaluating the impact of Tai Chi on maximal exercise capacity, balance and muscle strength in people with COPD. Comparison of Tai Chi and other interventions (i.e. breathing exercise or exercise) versus other interventions shows no superiority and no additional effects on symptom improvement nor on physical and psychosocial outcomes with Tai Chi. AUTHORS' CONCLUSIONS: No adverse events were reported, implying that Tai Chi is safe to practise in people with COPD. Evidence of very low to moderate quality suggests better functional capacity and pulmonary function in post-programme data for Tai Chi versus usual care. When Tai Chi in addition to other interventions was compared with other interventions alone, Tai Chi did not show superiority and showed no additional effects on symptoms nor on physical and psychosocial function improvement in people with COPD. With the diverse style and number of forms being adopted in different studies, the most beneficial protocol of Tai Chi style and number of forms could not be commented upon. Hence, future studies are warranted to address these topics. PMID- 27272130 TI - Ten-Year Changes in the Prevalence and Socio-Demographic Determinants of Physical Activity among Polish Adults Aged 20 to 74 Years. Results of the National Multicenter Health Surveys WOBASZ (2003-2005) and WOBASZ II (2013-2014). AB - INTRODUCTION: The aim of the study was to estimate ten-year changes in physical activity (PA) patterns and sociodemographic determinants among adult residents of Poland. METHODS: The study comprised two independent samples of randomly selected adults aged 20-74 years participating in the National Multicentre Health Survey WOBASZ (2003-2005; n = 14572) and WOBASZ II (2013-2014; n = 5694). In both surveys the measurements were performed by six academic centers in all 16 voivodships of Poland (108 measurement points in each survey). Sociodemographic data were collected by an interviewer-administered questionnaire in both surveys. Physical activity was assessed in three domains: leisure-time, occupational and commuting physical activity. RESULTS: Leisure-time PA changed substantially between the surveys (p<0.001). The prevalence of subjects being active on most days of week fell in both genders in the years 2003-2014 (37.4% vs 27.3% in men); 32.7% vs 28.3% in women. None or occasional activity increased from 49.6% to 56.8% in men, while remained stable in women (55.2% vs 54.9%). In both WOBASZ surveys the likelihood of physical inactivity was higher in less educated individuals, smokers and those living in large agglomerations (p<0.01). No significant changes were observed in occupational activity in men between the surveys, while in women percentage of sedentary work increased from 43.4% to % 49.4% (p<0.01). Commuting PA decreased significantly in both genders (p<0.001). About 79.3% of men and 71.3% of women reported no active commuting in the WOBASZ II survey. CONCLUSIONS: The observed unfavourable changes in PA emphasize the need for novel intervention concepts in order to reverse this direction. Further detailed monitoring of PA patterns in Poland is of particular importance. PMID- 27272134 TI - Too Much or Too Little? How Much Control Should Patients Have Over EHR Data? AB - Electronic health records (EHRs) have been promoted as a mechanism to overcome the fragmented healthcare system in the United States. The challenge that is being discussed is the rights of the patient to control the access to their EHRs' data and the needs of healthcare professionals to know health data to make the best treatment decisions for their patients. The Federal Trade Commission has asked those who store consumer information to comply with the Fair Information Practice Principles. In the EHR context, these principles give the rights to the patient to control who can see their health data and what components of the data are restricted from view. Control is not limited to patients, as it also includes parents of adolescent children. We suggest that the ongoing policy discussion include consideration of the precise questions patients will be asked when a need for data sharing arises. Further, patients should understand the relative risks that they face, and the degree to which their decisions will (or will not) significantly reduce the risk of a data breach. As various approaches are considered, it is important to address the relative resource requirements and the associated costs of each option. PMID- 27272132 TI - Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2. AB - Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members, the exact mechanism for the peripheral localization of APC remains unclear. Here we show that the heavy chain of kinesin-1 directly interacts with the APC C terminus, contributing to the peripheral localisation of APC in fibroblasts. In rat hippocampal neurons the kinesin-1 binding domain of APC is required for its axon tip enrichment. Moreover, we demonstrate that APC requires interactions with both kinesin-2 and kinesin-1 for this localisation. Underlining the importance of the kinesin-1 association, neurons expressing APC lacking kinesin-1-binding domain have shorter axons. The identification of this novel kinesin-1-APC interaction highlights the complexity and significance of APC localisation in neurons. PMID- 27272136 TI - Inspirational molecules. PMID- 27272135 TI - Forecasting the Emergency Department Patients Flow. AB - Emergency department (ED) have become the patient's main point of entrance in modern hospitals causing it frequent overcrowding, thus hospital managers are increasingly paying attention to the ED in order to provide better quality service for patients. One of the key elements for a good management strategy is demand forecasting. In this case, forecasting patients flow, which will help decision makers to optimize human (doctors, nurses...) and material(beds, boxs...) resources allocation. The main interest of this research is forecasting daily attendance at an emergency department. The study was conducted on the Emergency Department of Troyes city hospital center, France, in which we propose a new practical ED patients classification that consolidate the CCMU and GEMSA categories into one category and innovative time-series based models to forecast long and short term daily attendance. The models we developed for this case study shows very good performances (up to 91,24 % for the annual Total flow forecast) and robustness to epidemic periods. PMID- 27272137 TI - Are we ready for spray-on carbon nanotubes? PMID- 27272140 TI - Corrigendum: Feedback-driven self-assembly of symmetry-breaking optical metamaterials in solution. PMID- 27272139 TI - Metallic, magnetic and molecular nanocontacts. AB - Scanning tunnelling microscopy and break-junction experiments realize metallic and molecular nanocontacts that act as ideal one-dimensional channels between macroscopic electrodes. Emergent nanoscale phenomena typical of these systems encompass structural, mechanical, electronic, transport, and magnetic properties. This Review focuses on the theoretical explanation of some of these properties obtained with the help of first-principles methods. By tracing parallel theoretical and experimental developments from the discovery of nanowire formation and conductance quantization in gold nanowires to recent observations of emergent magnetism and Kondo correlations, we exemplify the main concepts and ingredients needed to bring together ab initio calculations and physical observations. It can be anticipated that diode, sensor, spin-valve and spin filter functionalities relevant for spintronics and molecular electronics applications will benefit from the physical understanding thus obtained. PMID- 27272141 TI - The joy of working together. PMID- 27272142 TI - Responses of corn physiology and yield to six agricultural practices over three years in middle Tennessee. AB - Different agricultural practices may have substantial impacts on crop physiology and yield. However, it is still not entirely clear how multiple agricultural practices such as tillage, biochar and different nutrient applications could influence corn physiology and yield. We conducted a three-year field experiment to study the responses of corn physiology, yield, and soil respiration to six different agricultural practices. The six treatments included conventional tillage (CT) or no tillage (NT), in combination with nitrogen type (URAN or chicken litter) and application method, biochar, or denitrification inhibitor. A randomized complete block design was applied with six replications. Leaf photosynthetic rate, transpiration, plant height, leaf area index (LAI), biomass, and yield were measured. Results showed that different agricultural practices had significant effects on plant leaf photosynthesis, transpiration, soil respiration, height, and yield, but not on LAI and biomass. The average corn yield in the NT-URAN was 10.03 ton/ha, 28.9% more than in the CT-URAN. Compared to the NT-URAN, the NT-biochar had lower soil respiration and similar yield. All variables measured showed remarkable variations among the three years. Our results indicated that no tillage treatment substantially increased corn yield, probably due to the preservation of soil moisture during drought periods. PMID- 27272144 TI - The 22nd annual prostate cancer foundation scientific retreat report. AB - The 22nd Annual Prostate Cancer Foundation (PCF) Scientific Retreat was convened in Washington, D.C. from October 8 to 10, 2015. This event is the foremost scientific conference in the world focusing on basic, translational, and clinical prostate cancer research with the highest potential for accelerating the understanding of prostate cancer biology and improving the lives and outcomes of prostate cancer patients. Topics highlighted during the 2015 Retreat included: (i) new strategies and treatments for localized high-risk, hormone-naive, oligometastatic, castrate-resistant, and treatment-refractory prostate cancer settings; (ii) the biology and genomics of tumor heterogeneity and tumor evolution; (iii) new understandings on the mechanisms and targeting of oncogenic drivers of prostate cancer; (iv) bioengineering of novel therapies and drug delivery methods; (v) innovative approaches to tumor immunotherapy; (vi) emerging molecular imaging technologies with improved sensitivity and specificity; and (vii) advancements in prognostic and predictive biomarkers and precision medicine strategies. Prostate 76:1037-1052, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272145 TI - Tracking Protein S-Fatty Acylation with Proteomics. AB - Recently, Hang and co-workers developed "acyl-PEG exchange" (APE), which allows the investigation of protein S-fatty acylation with mass-tag labelling and gel electrophoresis, methods that are accessible to any biochemistry laboratory. PMID- 27272143 TI - A replicator-specific binding protein essential for site-specific initiation of DNA replication in mammalian cells. AB - Mammalian chromosome replication starts from distinct sites; however, the principles governing initiation site selection are unclear because proteins essential for DNA replication do not exhibit sequence-specific DNA binding. Here we identify a replication-initiation determinant (RepID) protein that binds a subset of replication-initiation sites. A large fraction of RepID-binding sites share a common G-rich motif and exhibit elevated replication initiation. RepID is required for initiation of DNA replication from RepID-bound replication origins, including the origin at the human beta-globin (HBB) locus. At HBB, RepID is involved in an interaction between the replication origin (Rep-P) and the locus control region. RepID-depleted murine embryonic fibroblasts exhibit abnormal replication fork progression and fewer replication-initiation events. These observations are consistent with a model, suggesting that RepID facilitates replication initiation at a distinct group of human replication origins. PMID- 27272146 TI - Improved communication, understanding of risk perception and ethics related to ionising radiation. AB - In Europe today, institutions, media and the general public exchange information about ionizing radiation and associated risks. However, communication about ionising radiation with the general public has to be further improved, as has been previously highlighted by international responses to the 2011 accident in Japan. This article reports the main activities and findings in this field from the following three FP7 projects: EAGLE, PREPARE and OPERRA and discussed by a broad spectrum of stakeholders at the conference RICOMET 2015. These projects, among other aims, also investigate how communication about ionising radiation in different fields could be improved and harmonised, how radiological risks are perceived, how to encourage ethical considerations in all fields of nuclear applications and what kind of transdisciplinary research is needed. The projects relate to several domains; the first relates to education, training and communication, the second to nuclear emergency preparedness and response, and the third to research and development in the radiation protection field. Incorporation of stakeholder engagement activities such as the RICOMET conference broadens social and ethical aspects and takes them into account during coordination activities as well as during core scientific and nuclear research and development performed in the projects. These activities offered opportunities for moving closer to a citizen-centred ideal of risk communication in particular and nuclear research and development in general. PMID- 27272149 TI - 18F-FDG PET findings of pericardial lymphangiohemangioma. PMID- 27272147 TI - DNA damage-associated biomarkers in studying individual sensitivity to low-dose radiation from cardiovascular imaging. PMID- 27272150 TI - Frequent MUGA testing in a myeloma patient: A case-based ethics discussion. PMID- 27272152 TI - East Meets West: Synergy through Diversity. AB - The TCM hospital Bad Kotzting is historically the first inpatient facility in Germany with an emphasis on Traditional Chinese Medicine (TCM). The clinic's specialty is the multimodal treatment of somatic complaints in conjunction with acute psychological or psychiatric comorbidity. Most patients present with clinical problems of a high degree of chronicity and complexity. Over the past 25 years the treatment concept of the hospital has developed from a strictly TCM approach to a multimodal combination of TCM, psychosomatic medicine, and lifestyle medicine. This article outlines the admission and intake procedures and describes the process of determining the TCM diagnoses and treatment protocols. A typical case study illustrates this process in more details. Then, we present the various components of the psychotherapeutic and psychoeducational programs, including innovative approaches to lifestyle medicine. In conclusion, the treatment program at the TCM hospital Bad Kotzting has developed into a multimodal approach that synergistically intertwines diverse therapies drawn from Eastern and Western traditions, effectively combining the best approaches of both contexts. PMID- 27272151 TI - Genome-Wide Association Study in Immunocompetent Patients with Delayed Hypersensitivity to Sulfonamide Antimicrobials. AB - BACKGROUND: Hypersensitivity (HS) reactions to sulfonamide antibiotics occur uncommonly, but with potentially severe clinical manifestations. A familial predisposition to sulfonamide HS is suspected, but robust predictive genetic risk factors have yet to be identified. Strongly linked genetic polymorphisms have been used clinically as screening tests for other HS reactions prior to administration of high-risk drugs. OBJECTIVE: The purpose of this study was to evaluate for genetic risk of sulfonamide HS in the immunocompetent population using genome-wide association. METHODS: Ninety-one patients with symptoms after trimethoprim-sulfamethoxazole (TMP-SMX) attributable to "probable" drug HS based on medical record review and the Naranjo Adverse Drug Reaction Probability Scale, and 184 age- and sex-matched patients who tolerated a therapeutic course of TMP SMX, were included in a genome-wide association study using both common and rare variant techniques. Additionally, two subgroups of HS patients with a more refined clinical phenotype (fever and rash; or fever, rash and eosinophilia) were evaluated separately. RESULTS: For the full dataset, no single nucleotide polymorphisms were suggestive of or reached genome-wide significance in the common variant analysis, nor was any genetic locus significant in the rare variant analysis. A single, possible gene locus association (COL12A1) was identified in the rare variant analysis for patients with both fever and rash, but the sample size was very small in this subgroup (n = 16), and this may be a false positive finding. No other significant associations were found for the subgroups. CONCLUSIONS: No convincing genetic risk factors for sulfonamide HS were identified in this population. These negative findings may be due to challenges in accurately confirming the phenotype in exanthematous drug eruptions, or to unidentified gene-environment interactions influencing sulfonamide HS. PMID- 27272154 TI - [Thrombotic thrombocytopenic purpura after circumcision]. AB - After circumcision, a young man developed a wound healing disorder. After presenting to our hospital for further wound care, laboratory results showed acute renal failure with hemolytic anemia and thrombocytopenia, which led to the diagnosis of postoperative thrombotic thrombocytopenic purpura (TTP). After therapy with plasma exchange and immunosuppressive therapy with prednisolone and rituximab, the patient recovered with normalization of laboratory results. The TTP is associated with low activity of ADAMTS13 with microvascular platelet aggregation and hemolytic anemia. PMID- 27272153 TI - Nurse safety outcomes: old problem, new solution - the differentiating roles of nurses' psychological capital and managerial support. AB - AIM: The aim of this study was to examine the impacts of nurses' psychological capital and managerial support, plus specific safety interventions (managerial safety priorities, safety training satisfaction), on nurses' in-role safety performance. BACKGROUND: Most hospitals in industrialized countries have adopted selective (often the least costly) aspects of safety, usually related to safety policies. However, patient safety remains a challenge in many countries. Research shows that training can be used to upskill employees in psychological capital, with statistically significant organizational and employee benefits, but this area is under-researched in nursing. DESIGN: Data were collected using a survey based, self-report strategy. The emerging patterns of data were then compared with the findings of previous research. METHODS: Quantitative survey data were collected during 2014 from 242 nurses working in six Australian hospitals. Two models were tested and analysed using covariance-based Structural Equation Modelling. RESULTS: Psychological capital and safety training satisfaction were important predictors of nurses' in-role safety performance and as predictors of nurses' perceptions of whether management implements what it espouses about safety ('managerial safety priorities'). Managerial support accounted for just under a third of psychological capital and together, psychological capital and managerial support, plus satisfaction with safety training, were important to nurses' perceptions of in-role safety performance. CONCLUSION: Organizations are likely to benefit from upskilling nurses and their managers to increase nurses' psychological capital and managerial support, which then will enhance nurses' satisfaction with training and in-role safety performance perceptions. PMID- 27272155 TI - High-Throughput 3D Tumor Spheroid Screening Method for Cancer Drug Discovery Using Celigo Image Cytometry. AB - Oncologists have investigated the effect of protein or chemical-based compounds on cancer cells to identify potential drug candidates. Traditionally, the growth inhibitory and cytotoxic effects of the drugs are first measured in 2D in vitro models, and then further tested in 3D xenograft in vivo models. Although the drug candidates can demonstrate promising inhibitory or cytotoxicity results in a 2D environment, similar effects may not be observed under a 3D environment. In this work, we developed an image-based high-throughput screening method for 3D tumor spheroids using the Celigo image cytometer. First, optimal seeding density for tumor spheroid formation was determined by investigating the cell seeding density of U87MG, a human glioblastoma cell line. Next, the dose-response effects of 17 AAG with respect to spheroid size and viability were measured to determine the IC50 value. Finally, the developed high-throughput method was used to measure the dose response of four drugs (17-AAG, paclitaxel, TMZ, and doxorubicin) with respect to the spheroid size and viability. Each experiment was performed simultaneously in the 2D model for comparison. This detection method allowed for a more efficient process to identify highly qualified drug candidates, which may reduce the overall time required to bring a drug to clinical trial. PMID- 27272156 TI - A Low-Cost and Fast Real-Time PCR System Based on Capillary Convection. AB - A low-cost and fast real-time PCR system in a pseudo-isothermal manner with disposable capillary tubes based on thermal convection for point-of-care diagnostics is developed and tested. Once stable temperature gradient along the capillary tube has been established, a continuous circulatory flow or thermal convection inside the capillary tube will repeatedly transport PCR reagents through temperature zones associated with the DNA denaturing, annealing, and extension stages of the reaction. To establish stable temperature gradient along the capillary tube, a dual-temperature heating strategy with top and bottom heaters is adopted here. A thermal waveguide is adopted for precise maintenance of the temperature of the top heater. An optimized optical network is developed for monitoring up to eight amplification units for real-time fluorescence detection. The system performance was demonstrated with repeatable detection of influenza A (H1N1) virus nucleic acid targets with a limit of detection of 1.0 TCID50/mL within 30 min. PMID- 27272158 TI - Strategies to Build Authorship Competence Among PhD Students. AB - Publication in refereed journals is an important responsibility of PhD-prepared nurses. Specialized writing skills are crucial for effective professional publication. The capacity to develop and publish articles is best learned during doctoral education. This Western Journal of Nursing Research Editorial Board Special Article addresses multi-dimensional strategies to develop authorship competence among doctoral students. The article outlines structured PhD program experiences to provide the context for students to develop authorship capacity. The authors identify multi-faceted faculty endeavors and student activities that are essential to foster authorship competence. Students who embrace opportunities to acquire authorship qualifications will be well prepared for their post graduation role as stewards of the nursing discipline. PMID- 27272157 TI - Enhanced antitumor activity and attenuated cardiotoxicity of Epirubicin combined with Paeonol against breast cancer. AB - Epirubicin is widely used for the therapy of various breast cancers. However, it has serious adverse side effects, particularly cardiotoxicity, which can cause irreversible damage in patients. Paeonol, an active component from Moutan Cortex, enhances antitumor activity of antineoplastics and reduces toxicities induced by chemotherapeutics. In this study, we investigated the anticancer activity of Paeonol in combination with Epirubicin against breast cancer and the alleviated effect of Paeonol on cardiotoxicity induced by Epirubicin. The apoptosis results and the coefficient of drug interaction values suggested significantly synergistic in combination of Paeonol and Epirubicin to 4T1 and MCF-7 cells. We further examined antitumor activities of Paeonol or/and Epirubicin in vivo in BALB/c mice and found that co-treatment of Paeonol and Epirubicin had a synergistic inhibitory effect on tumor growth and enhanced apoptosis in tumors in vivo compared with Epirubicin alone. Increased apoptosis was associated with the activation of apoptosis-related proteins including PARP, Bax, caspase 3, and inhibition of p38/JNK/ERK MAPKs. Moreover, Paeonol exhibited a mitigative effect on Epirubicin-induced cardiotoxicity through suppressing NF-kB pathway. In conclusion, Paeonol (a) enhanced the antitumor activity of Epirubicin in a synergistic manner against breast cancer cells via inhibiting p38/JNK/ERK MAPKs and (b) alleviated Epirubicin-induced cardiotoxicity by suppressing NF-kB pathway. These findings suggest that combination of Paeonol and Epirubicin is potentially applicable for breast cancer treatment. PMID- 27272159 TI - Factors Associated With Medication Adherence Among Medical-Aid Beneficiaries With Hypertension. AB - The purpose was to examine factors associated with medication adherence among medical-aid beneficiaries with hypertension using the Expanded Behavioral Model of Health Services Utilization. A cross-sectional study was conducted with a convenient sample of 289 patients. The instruments included scales to measure medication adherence, health literacy, general self-efficacy, and pros and cons of chronic disease management. Data collection was performed between February and March 2011. A hierarchical regression analysis was performed. The study found that 25.6% to 34.6% had low motivation and low knowledge regarding medication adherence. Those with higher health literacy and higher self-efficacy scores were more likely to have higher medication adherence, whereas widowed and those who perceived more cons of chronic disease management were more likely to have lower medication adherence than their counterparts (p < .05). Interventions incorporating significant factors associated with medication adherence are required to enhance medication adherence and to prevent complications associated with medication non-adherence. PMID- 27272160 TI - Lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy. AB - We reported a case of an 11-year-old girl admitted to our hospital for goiter, tachycardia, sweating, and visible and palpable thyroid. Thyroid function tests revealed a low thyrotropin level (<0.004 mIU/L) and elevated free thyroxine level (3.4 ng/ dL) diagnosed with Graves' disease and treated with methimazole. This anti-thyroid drug is recommended as first-line treatment in children with Graves' disease because it produces minor adverse effects with respect to propylthiouracil. She developed a lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy. The symptoms resolved after discontinuation of methimazole and treatment with an antihistamine and a corticosteroid. Furthermore, the treatment was changed to propylthiouracil without any adverse effects. According to current literature this is the first case of cutaneous figurate erythema related to methimazole, different from other well-known reactions such as skin eruption or urticaria. PMID- 27272161 TI - Fluticasone/formoterol association favors long-lasting decrease in bronchial reactivity to methacholine and weekly PEF variability. AB - Inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) association offers a better asthma control than a higher steroid dose with short-acting beta agonists as needed. In this study, we evaluated the effect of the association on bronchial hyperreactivity (BHR) and peak expiratory flow (PEF) variability, as such parameters are positively correlated with increased asthma morbidity and exacerbations. Thirty-six adult patients with mild persistent asthma were enrolled. After a 7-day run-in, they were randomly assigned to three therapy regimens for 6 weeks: Group 1, fluticasone 125 MUg + formoterol 5 MUg in the same device; Group 2, fluticasone 125 MUg + formoterol 12 MUg as needed; Group 3, fluticasone 250 MUg + formoterol 12 MUg as needed. We evaluated changes induced in weekly PEF variability (measured during the entire study and 4 weeks of follow up) and pre- and post-study PD20 methacholine (MCH). Weekly PEF variability decreased in all groups during treatment with the greatest reduction in Group 1, followed by Group 3, and finally Group 2. During the follow-up, no significant changes were detected in Group 1, whereas a trend towards an increased variability was found in Groups 2 and 3. Post-treatment PD20 MCH was significantly higher versus the pre-treatment. The increase observed in Group 1 was significantly higher compared to Groups 2 and 3 and that observed in Group 3 in respect to Group 2. The study proves that both BHR and PEF variability are influenced by ICS. This effect was greater with fluticasone/formoterol association compared to fluticasone alone with formoterol as needed even at higher steroid dose. PMID- 27272162 TI - Renal tubular function and urinary N-acetyl-beta-d-glucosaminidase and kidney injury molecule-1 levels in asthmatic children. AB - BACKGROUND: Asthma is a chronic inflammatory disorder of the airways which results in chronic hypoxia. Chronic hypoxia and inflammation can affect renal tubular function. OBJECTIVES: The aim of this study was to investigate renal tubular function and early kidney injury molecules such as urinary N-acetyl betaglucosaminidase (NAG) and kidney injury molecule-1 (KIM-1) excretion in children with asthma. METHODS: Enrolled in the study were 73 children diagnosed with asthma and 65 healthy age- and gender-matched control subjects. Urine pH, sodium, phosphorus, potassium, microalbumin, creatinine, NAG, KIM-1, and serum creatinine, sodium, phosphorus were evaluated. The diagnosis of asthma and classification of mild or moderate were done according to the Global Initiative for Asthma guidelines. RESULTS: Serum sodium, phosphorus, creatinine, and urinary microalbumin were within normal levels in the both groups. Urinary pH, sodium, potassium, phosphorus, microalbumin, and KIM-1 excretions were similar between the control and study groups. Tubular phosphorus reabsorption was within normal limits in two groups. Urine NAG was elevated in the study group (P = 0.001). Urinary KIM-1 and NAG levels were positively correlated (r = 0.837; P = 0.001). When children with mild and moderate asthma were compared, all of the parameters were similar (P >0.05). CONCLUSIONS: This study showed that chronic asthma can lead to subtle renal impacts. We suggest that in children with asthma, urinary NAG level is a more valuable parameter to show degree of renal tubular injury than markers such as microalbumin and KIM-1. Chronic hypoxy and inflammation probably contributes to these subclinical renal effects. PMID- 27272164 TI - Correction: Captive Reptile Mortality Rates in the Home and Implications for the Wildlife Trade. AB - [This corrects the article DOI: 10.1371/journal.pone.0141460.]. PMID- 27272163 TI - Disruption of Slc52a3 gene causes neonatal lethality with riboflavin deficiency in mice. AB - Homeostasis of riboflavin should be maintained by transporters. Previous in vitro studies have elucidated basic information about riboflavin transporter RFVT3 encoded by SLC52A3 gene. However, the contribution of RFVT3 to the maintenance of riboflavin homeostasis and the significance in vivo remain unclear. Here, we investigated the physiological role of RFVT3 using Slc52a3 knockout (Slc52a3-/-) mice. Most Slc52a3-/- mice died with hyperlipidemia and hypoglycemia within 48 hr after birth. The plasma and tissue riboflavin concentrations in Slc52a3-/- mice at postnatal day 0 were dramatically lower than those in wild-type (WT) littermates. Slc52a3-/- fetuses showed a lower capacity of placental riboflavin transport compared with WT fetuses. Riboflavin supplement during pregnancy and after birth reduced neonatal death and metabolic disorders. To our knowledge, this is the first report to indicate that Rfvt3 contributes to placental riboflavin transport, and that disruption of Slc52a3 gene caused neonatal mortality with hyperlipidemia and hypoglycemia owing to riboflavin deficiency. PMID- 27272165 TI - Management Options During the 2011-2012 Drought on the Apalachicola River: A Systems Dynamic Model Evaluation. AB - The Apalachicola-Chattahoochee-Flint River basin (ACF) is a large watershed in the southeastern United States. In 2012, the basin experienced the second year of a severe drought and the third multi-year drought in the last 15 years. During severe droughts, low reservoir and river levels can cause economic and ecological impacts to the reservoir, river, and estuarine ecosystems. During drought, augmenting Apalachicola River discharge through upstream reservoir releases and demand management are intuitive and often-suggested solutions to minimizing downstream effects. We assessed whether the existing reservoir system could be operated to minimize drought impacts on downstream water users and ecosystems through flow augmentation. Our analysis finds that in extreme drought such as observed during 2012, increases in water releases from reservoir storage are insufficient to even increase Apalachicola River discharge to levels observed in the 2007 drought. This suggests that there is simply not enough water available in managed storage to offset extreme drought events. Because drought frequency and intensity is predicted to increase under a variety of climate forecasts, our results demonstrate the need for a critical assessment of how water managers will meet increasing water demands in the ACF. Key uncertainties that should be addressed include (1) identifying the factors that led to extremely low Flint River discharge in 2012, and (2) determining how water "saved" via demand management is allocated to storage or passed to downstream ecosystem needs as part of the ongoing revisions to the ACF Water Control Manual by the US Army Corps of Engineers. PMID- 27272166 TI - Evaluating the Characteristics of Social Vulnerability to Wildfire: Demographics, Perceptions, and Parcel Characteristics. AB - A large body of research focuses on identifying patterns of human populations most at risk from hazards and the factors that help explain performance of mitigations that can help reduce that risk. One common concept in such studies is social vulnerability-human populations' potential exposure to, sensitivity from and ability to reduce negative impacts from a hazard. While there is growing interest in social vulnerability for wildfire, few studies have critically evaluated the characteristics that scholars often indicate influence social vulnerability to that hazard. This research utilizes surveys, wildfire simulations, and GIS data to test the relationships between select demographic, perceptual and parcel characteristics of property owners against empirically simulated metrics for wildfire exposure or wildfire-related damages and their performance of mitigation actions. Our results from Flathead County, MT, USA, suggest that parcel characteristics such as property value, building value, and the year structures were built explaining a significant amount of the variance in elements of social vulnerability. Demographic characteristics commonly used in social vulnerability analysis did not have significant relationships with measures of wildfire exposure or vulnerability. Part-time or full-time residency, age, perceived property risk, and year of development were among the few significant determinants of residents' performance of fuel reduction mitigations, although the significance of these factors varied across the levels of fuel reduction performed by homeowners. We use these and other results to argue for a renewed focus on the finer-scale characteristics that expose some populations to wildfire risk more than others. PMID- 27272167 TI - Clinical trials with direct oral anticoagulants for stroke prevention in atrial fibrillation: how representative are they for real life patients? AB - PURPOSE: To identify the proportion of real-life patients with atrial fibrillation (AF) eligible for direct oral anticoagulant (DOAC) therapy, based on the inclusion and exclusion criteria used in the clinical studies and based on the officially approved indications as mentioned in the Summary of Product Characteristics (SmPC). METHODS: Data for this retrospective cross-sectional study was extracted from the UZ Brussel Stroke Registry, containing anonymized data of 2205 patients with a suspected stroke. Characteristics of patients with documented AF were compared with the patient characteristics in clinical trials and the approved indications in the SmPC. RESULTS: Data of 468 patients with AF was analyzed. Based on the selection criteria of the clinical trials, significantly less patients were eligible for treatment with rivaroxaban compared to dabigatran etexilate (39.3 versus 47.6 %; p = 0.010), but not compared to apixaban (45.5 %; p = 0.055). Based on the indications and contraindications in the SmPC, significantly fewer patients were eligible for apixaban compared to dabigatran etexilate and rivaroxaban (62.0 % for apixaban, 72.9 % for dabigatran etexilate, and 75.6 % for rivaroxaban; p < 0.001 and p < 0.001, respectively). Significantly, more patients were eligible for DOAC therapy based on the indications and contraindications in the SmPC compared to the inclusion and exclusion criteria of the clinical trials (72.9 versus 47.6 %; p < 0.001 for dabigatran; 75.6 versus 39.3 %; p < 0.001 for rivaroxaban and 62.0 versus 45.5 %; p < 0.001 for apixaban). CONCLUSION: When taking into account the selection criteria from the pivotal clinical trials with DOACs for stroke prevention in AF, less than half of real-life patients are eligible for therapy with one of the DOACs. However, the indications mentioned in the SmPCs of these drugs are less strict. PMID- 27272168 TI - QEEG and LORETA in Teenagers With Conduct Disorder and Psychopathic Traits. AB - BACKGROUND: Few studies have investigated the impact of the psychopathic traits on the EEG of teenagers with conduct disorder (CD). To date, there is no other research studying low-resolution brain electromagnetic tomography (LORETA) technique using quantitative EEG (QEEG) analysis in adolescents with CD and psychopathic traits. OBJECTIVE: To find electrophysiological differences specifically related to the psychopathic traits. The current investigation compares the QEEG and the current source density measures between adolescents with CD and psychopathic traits and adolescents with CD without psychopathic traits. METHODS: The resting EEG activity and LORETA for the EEG fast spectral bands were evaluated in 42 teenagers with CD, 25 with and 17 without psychopathic traits according to the Antisocial Process Screening Device. All adolescents were assessed using the DSM-IV-TR criteria. The EEG visual inspection characteristics and the use of frequency domain quantitative analysis techniques (narrow band spectral parameters) are described. RESULTS: QEEG analysis showed a pattern of beta activity excess on the bilateral frontal-temporal regions and decreases of alpha band power on the left central-temporal and right frontal-central-temporal regions in the psychopathic traits group. Current source density calculated at 17.18 Hz showed an increase within fronto-temporo-striatal regions in the psychopathic relative to the nonpsychopathic traits group. CONCLUSIONS: These findings indicate that QEEG analysis and techniques of source localization may reveal differences in brain electrical activity among teenagers with CD and psychopathic traits, which was not obvious to visual inspection. Taken together, these results suggest that abnormalities in a fronto-temporo-striatal network play a relevant role in the neurobiological basis of psychopathic behavior. PMID- 27272169 TI - Intralipid in acute caffeine intoxication: a case report. AB - Caffeine is arguably the most widely used stimulant drug in the world. Here we describe a suicide attempt involving caffeine overdose whereby the patient's severe intoxication was successfully treated with the prompt infusion of Intralipid. A 19-year-old man was found in an agitated state at home by the volunteer emergency team about 1 h after the intentional ingestion of 40 g of caffeine (tablets). His consciousness decreased rapidly, followed quickly by seizures, and electrocardiographic monitoring showed ventricular fibrillation. Advanced life support maneuvers were started immediately, with the patient defibrillated 10 times and administered 5 mg epinephrine in total and 300 + 150 mg of amiodarone (as well as lidocaine and magnesium sulfate). The cardiac rhythm eventually evolved to asystole, necessitating the intravenous injection of epinephrine to achieve the return of spontaneous circulation. However, critical hemodynamic instability persisted, with the patient's cardiac rhythm alternating between refractory irregular narrow complex tachycardia and wide complex tachycardia associated with hypotension. In an attempt to restore stability we administered three successive doses of Intralipid (120 + 250 + 100 mg), which successfully prevented a severe cardiovascular collapse due to a supra-lethal plasma caffeine level (>120 mg/L after lipid emulsion). The patient survived without any neurologic complications and was transferred to a psychiatric ward a few days later. The case emphasizes the efficacy of intravenous lipid emulsion in the resuscitation of patients from non-local anesthetic systemic toxicity. Intralipid appears to act initially as a vehicle that carries the stimulant drug away from heart and brain to less well-perfused organs (scavenging mechanism) and then, with a sufficient drop in the caffeine concentration, possibly as a tonic to the depressed heart. PMID- 27272171 TI - Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis. AB - BACKGROUND: ABT-494 is a potent and selective Janus kinase (JAK) 1 inhibitor being developed for the treatment of several autoimmune disorders, with potential for an improved safety profile compared with non-selective JAK inhibitors. This work characterized the pharmacokinetics, safety, and tolerability of ABT-494 following single and multiple dosing of the immediate-release formulation. METHODS: ABT-494 single (1-48 mg or placebo; n = 56) and multiple (3-24 mg or placebo twice daily for 14 days; n = 44) doses in healthy subjects, as well as multiple doses (3-24 mg or placebo twice daily for 27 days; n = 14) in subjects with rheumatoid arthritis (RA) on a background of methotrexate were evaluated. Pharmacokinetic samples were collected and safety and tolerability were assessed. RESULTS: ABT-494 followed bi-exponential disposition, with a terminal elimination half-life of 6-16 h and a functional half-life, calculated from maximum observed plasma concentration (C max) to trough plasma concentration (C trough) ratio at steady state, of 3-4 h. ABT-494 exposure was approximately dose proportional over the 3-36 mg dose range, with no significant accumulation with repeated dosing. In subjects with RA, no pharmacokinetic interaction between ABT-494 and methotrexate was observed. The fraction of ABT-494 dose eliminated in urine as unchanged ABT 494 was 14-25 %. All treatment-emergent adverse events (TEAEs) were mild or moderate in severity, with headache being the most frequently observed TEAE (15.6 % for ABT-494 vs. 16.7 % for placebo) after multiple twice-daily administration to healthy subjects. No clinically significant changes in laboratory parameters, vital signs, or electrocardiogram findings in healthy or RA subjects were observed. CONCLUSIONS: The favorable pharmacokinetics, safety, and tolerability results from these studies supported further evaluations of ABT-494 in phase IIb dose-ranging trials in RA and Crohn's disease. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ) identifier: NCT01741493. PMID- 27272172 TI - Clinical significance of a second-line chemotherapy regimen with paclitaxel, ifosfamide and nedaplatin for metastatic urothelial carcinoma after failure of cisplatin-based chemotherapy. AB - OBJECTIVE: Cisplatin-based chemotherapy has been commonly used as the first-line chemotherapy for metastatic urothelial carcinoma. However, after failure of the first-line cisplatin-based chemotherapy, there is no established standard second line chemotherapy. Starting in 2006, paclitaxel, ifosfamide and nedaplatin chemotherapy has been performed as the second-line chemotherapy in our institution. Here, we report the treatment results of paclitaxel, ifosfamide and nedaplatin chemotherapy. METHODS: From 2006 to 2015, 33 patients with metastatic urothelial carcinoma were treated with paclitaxel, ifosfamide and nedaplatin chemotherapy after failure of first-line cisplatin-based chemotherapy in our institution. We retrospectively examined the treatment outcome and predictive factors for therapeutic effects of paclitaxel, ifosfamide and nedaplatin. The median age, treatment cycle and follow-up period were 62.5 years, 3 cycles and 10.4 months, respectively. RESULTS: The median overall survival and progression free survival were 10.4 and 3.5 months, respectively. Complete and partial responses were found in 3 and 7 patients, respectively, with an overall response rate of 30%. All patients developed grade 3-4 neutropenia, but there was no treatment-related death. In multivariate analysis, the only prognostic factor for progression-free survival was 24-hour urinary creatinine clearance. CONCLUSIONS: A paclitaxel, ifosfamide and nedaplatin regimen as second-line chemotherapy for metastatic urothelial carcinoma was effective and tolerable. Moreover, paclitaxel, ifosfamide and nedaplatin chemotherapy may be more effective in patients with satisfactory renal function. PMID- 27272173 TI - Clinical practice patterns for upper tract urothelial carcinoma: a nationwide survey in Japan. AB - OBJECTIVE: A comprehensive survey has not yet been conducted to investigate care patterns by urologists for the management of upper tract urothelial carcinoma. METHODS: We conducted a nationwide survey for urologists treating upper tract urothelial carcinoma patients. The questionnaire was approved by the Japanese Urological Association and sent by mail in February 2014 to 1119 institutes in Japan. We identified 627 responders for this study. RESULTS: Our survey demonstrated that (i) the mean number of radical nephroureterectomy cases per institution in 2013 was 7.6, (ii) the main detecting tool for upper tract urothelial carcinoma is contrast-enhanced computed tomography, (iii) the need for ureteroscopic evaluations is highly dependent on voiding urine cytology results, (iv) 67% of urologists always or often perform radical nephroureterectomy by laparoscopic surgery, (v) more than half of the urologists do not aggressively perform lymph node dissection, (vi) 75% of the urologists perform bladder cuff incision through an extravesical approach, (vii) urologists perform kidney sparing surgery following various indications, (viii) 59% of the urologists always perform adjuvant systemic chemotherapy for high-risk upper tract urothelial carcinoma patients, (ix) the combination of gemcitabine and cisplatin is the most frequent chemo-regimen for metastatic upper tract urothelial carcinoma, and gemcitabine and cisplatin with dose reductions is also the first choice even in patients with impaired renal function and (x) 10.5% of urologists always or sometimes perform single intravesical chemotherapy immediately after radical nephroureterectomy. CONCLUSIONS: The management strategy for upper tract urothelial carcinoma has changed with the introduction of new devices and development of instruments. The lack of clear evidence for relatively uncommon upper tract urothelial carcinoma affects the consistency of its treatment strategies. PMID- 27272174 TI - Staging discrepancies between Hospital-Based Cancer Registry and Diagnosis Procedure Combination data. PMID- 27272175 TI - The effect of lymphadenectomy on survival and recurrence in patients with ovarian cancer: a systematic review and meta-analysis. AB - OBJECTIVE: Our objective was to perform a meta-analysis examining the effectiveness of lymphadenectomy in patients with ovarian cancer. METHODS: PubMed and CENTRAL databases were searched on 15 November 2015 using the terms 'lymphadenectomy', 'ovarian cancer', 'dissection', 'para-aortic', 'pelvic' and survival. Prospective and retrospective studies comparing the outcomes of surgery with or without lymphadenectomy were included. Outcomes were 5-year overall survival, progression-free survival and recurrence rate. RESULTS: Of the 556 studies identified, 3 randomized controlled trials and 11 retrospective studies were included. Lymphadenectomy was associated with greater 5-year overall survival than no lymphadenectomy (pooled odds ratio = 1.58, 95% confidence interval: 1.41-1.77, p < 0.001). There was no difference in progression-free survival between the groups (pooled overall survival = 1.62, 95% confidence interval: 0.82-3.21, p = 0.168). Lymphadenectomy was associated with greater progression-free survival in randomized clinical trials (pooled overall survival = 1.57, 95% confidence interval: 1.11-2.21, p = 0.010), but not in retrospective studies. Lymphadenectomy was associated with a significantly lower recurrence rate (pooled overall survival = 0.51, 95% confidence interval: 0.30-0.85, p = 0.011). Lymphadenectomy was associated with greater 5-year overall survival in patients with both early and advanced stage cancer, but was associated with greater progression-free survival and lower recurrence rate only in patients with advanced stage cancer. CONCLUSION: Lymphadenectomy is associated with greater 5 year overall survival in patients with early and advanced stage ovarian cancer, but an effect on progression-free survival and recurrence rate was only found in patients with advanced stage ovarian cancer. PMID- 27272176 TI - Multiplexing Genetic and Nucleosome Positioning Codes: A Computational Approach. AB - Eukaryotic DNA is strongly bent inside fundamental packaging units: the nucleosomes. It is known that their positions are strongly influenced by the mechanical properties of the underlying DNA sequence. Here we discuss the possibility that these mechanical properties and the concomitant nucleosome positions are not just a side product of the given DNA sequence, e.g. that of the genes, but that a mechanical evolution of DNA molecules might have taken place. We first demonstrate the possibility of multiplexing classical and mechanical genetic information using a computational nucleosome model. In a second step we give evidence for genome-wide multiplexing in Saccharomyces cerevisiae and Schizosacharomyces pombe. This suggests that the exact positions of nucleosomes play crucial roles in chromatin function. PMID- 27272177 TI - D-Serine Is a Substrate for Neutral Amino Acid Transporters ASCT1/SLC1A4 and ASCT2/SLC1A5, and Is Transported by Both Subtypes in Rat Hippocampal Astrocyte Cultures. AB - N-methyl-D-aspartate (NMDA) receptors play critical roles in synaptic transmission and plasticity. Activation of NMDA receptors by synaptically released L-glutamate also requires occupancy of co-agonist binding sites in the tetrameric receptor by either glycine or D-serine. Although D-serine appears to be the predominant co-agonist at synaptic NMDA receptors, the transport mechanisms involved in D-serine homeostasis in brain are poorly understood. In this work we show that the SLC1 amino acid transporter family members SLC1A4 (ASCT1) and SLC1A5 (ASCT2) mediate homo- and hetero-exchange of D-serine with physiologically relevant kinetic parameters. In addition, the selectivity profile of D-serine uptake in cultured rat hippocampal astrocytes is consistent with uptake mediated by both ASCT1 and ASCT2. Together these data suggest that SLC1A4 (ASCT1) may represent an important route of Na-dependent D-serine flux in the brain that has the ability to regulate extracellular D-serine and thereby NMDA receptor activity. PMID- 27272178 TI - Direct Measurement of Single-Molecule DNA Hybridization Dynamics with Single-Base Resolution. AB - Herein, we report label-free detection of single-molecule DNA hybridization dynamics with single-base resolution. By using an electronic circuit based on point-decorated silicon nanowires as electrical probes, we directly record the folding/unfolding process of individual hairpin DNAs with sufficiently high signal-to-noise ratio and bandwidth. These measurements reveal two-level current oscillations with strong temperature dependence, enabling us to determine the thermodynamic and kinetic properties of hairpin DNA hybridization. More importantly, successive, stepwise increases and decreases in device conductance at low temperature on a microsecond timescale are successfully observed, indicating a base-by-base unfolding/folding process. The process demonstrates a kinetic zipper model for DNA hybridization/dehybridization at the single base pair level. This measurement capability promises a label-free single-molecule approach to probe biomolecular interactions with fast dynamics. PMID- 27272179 TI - Acute invasive fungal rhinosinusitis: our experience with 18 cases. AB - Acute invasive fungal rhinosinusitis (AIFRS) is a rapidly progressive life threatening infection that is seen most commonly among immunocompromised patients. We present a case series of 18 patients clinically and histopathologically diagnosed with AIFRS with a mean follow-up of 9.11 +/- 2.51 months (range 6-17). Demographic data, apparent symptoms and signs, underlying disorders, and outcomes are discussed. The mean age was 39.56 +/- 20.66 years (range 2-75). The most common underlying diseases were diabetes mellitus (50 %) and leukemia (44.44 %). Mucosal biopsy confirmed fungal invasion of the nasal mucosa in all cases. The main fungi were Rhizopus oryzae (55.56 %), Absidia mucor (16.67 %), and Aspergillus fumigatus (27.78 %). Headache and facial pain (77.8 %), facial paresthesia (55.6 %), and ophthalmoplegia (33.3 %) were the most common symptoms and signs. Computed tomography and endoscopic findings showed various stages of sinonasal (100 %), pterygopalatine fossa (55.56 %), orbital (44.45 %), and cerebral (5.56 %) involvement. All patients underwent serial surgical debridement (3.78 +/- 1.80 times; range 2-8) simultaneously with systemic antifungal therapy and proper management of the underlying disease. The most extreme case with brain involvement survived and recovered with no evidence of recurrent disease following treatment. All patients were considered cured after two endoscopic negative histopathologic evaluations. Three patients (16.67 %) died, one from uncontrolled leukemia and two due to renal failure. AIFRS is a potentially fatal condition, however, early diagnosis and management of the underlying disease accompanied with systemic antifungal and aggressive serial surgical intervention appears to be effective in reducing mortality in most patients. PMID- 27272180 TI - Ameloblastoma: 25 Year Experience at a Single Institution. AB - Ameloblastoma is a rare, locally aggressive odontogenic neoplasm, accounting for fewer than 1 % of head and neck tumors. Recent literature suggests that the initial surgical approach and histologic growth patterns are the most important prognostic determinants in ameloblastoma. The aim of this study was to compare the clinical presentation, management, and outcomes of patients with ameloblastoma with data reported in the literature; the study spanned 2 decades at a single institution. The institution's database was searched for all patients with pathologically confirmed ameloblastoma, diagnosed between 1990 and 2015. The data collected included sex, age, clinical and imaging findings, management, histologic pattern, clearance of surgical margins, length of follow-up, time to recurrence, and disease-related mortality. The potential risk factors of recurrence were evaluated using log-rank test, proportional hazard model, and Fisher exact test. Review of the database yielded 54 patients with pathologically confirmed ameloblastoma and follow-up. Recurrence was noted in 13 (24 %) patients. Surgical approach was associated with the risk of recurrence (6.1 % following radical resection vs. 52 % following limited surgery, p = 0.002). There were trends toward higher recurrence rate in the group with pathologically documented positive margins (p = 0.054) and in follicular ameloblastoma (p = 0.35). Transformation into ameloblastic carcinoma was identified in two patients. There was no disease-related mortality. Our study confirms the recent data regarding the importance of radical surgical resection in management of ameloblastoma. Surgical approach appears to be the strongest predictor of tumor clearance. PMID- 27272181 TI - Social relationships and cognitive decline: a systematic review and meta-analysis of longitudinal cohort studies. AB - BACKGROUND: Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta analysis to investigate the relation between poor social relationships and cognitive decline. METHODS: MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these. RESULTS: We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies. CONCLUSIONS: Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies. PMID- 27272183 TI - Cohort Profile: The Tasmanian Longitudinal Health STUDY (TAHS). PMID- 27272182 TI - Trajectories of function and biomarkers with age: the CHS All Stars Study. AB - BACKGROUND: Multimorbidity is a major driver of physical and cognitive impairment, but rates of decline are also related to ageing. We sought to determine trajectories of decline in a large cohort by disease status, and examined their correspondence with biomarkers of ageing processes including growth hormone, sex steroid, inflammation, visceral adiposity and kidney function pathways. METHODS: We have followed the 5888 participants in the Cardiovascular Health Study (CHS) for healthy ageing and longevity since 1989-90. Gait speed, grip strength, modified mini-mental status examination (3MSE) and the digit symbol substitution test (DSST) were assessed annually to 1998-99 and again in 2005-06. Insulin-like growth hormone (IGF-1), dehydroepiandrosterone sulphate (DHEAS), interleukin-6 (IL-6), adiponectin and cystatin-C were assessed 3-5 times from stored samples. Health status was updated annually and dichotomized as healthy vs not healthy. Trajectories for each function measure and biomarker were estimated using generalized estimating equations as a function of age and health status using standardized values. RESULTS: Trajectories of functional decline showed strong age acceleration late in life in healthy older men and women as well as in chronically ill older adults. Adiponectin, IL-6 and cystatin-C tracked with functional decline in all domains; cystatin-C was consistently associated with functional declines independent of other biomarkers. DHEAS was independently associated with grip strength and IL-6 with grip strength and gait speed trajectories. CONCLUSIONS: Functional decline in late life appears to mark a fundamental ageing process in that it occurred and was accelerated in late life regardless of health status. Cystatin C was most consistently associated with these functional declines. PMID- 27272185 TI - Cohort Profile: The HIV Atlanta Veterans Affairs Cohort Study (HAVACS). PMID- 27272184 TI - Measles outbreak response vaccination in the Federated States of Micronesia. PMID- 27272187 TI - A Chromosome 7 Pericentric Inversion Defined at Single-Nucleotide Resolution Using Diagnostic Whole Genome Sequencing in a Patient with Hand-Foot-Genital Syndrome. AB - Next generation sequencing methodologies are facilitating the rapid characterisation of novel structural variants at nucleotide resolution. These approaches are particularly applicable to variants initially identified using alternative molecular methods. We report a child born with bilateral postaxial syndactyly of the feet and bilateral fifth finger clinodactyly. This was presumed to be an autosomal recessive syndrome, due to the family history of consanguinity. Karyotype analysis revealed a homozygous pericentric inversion of chromosome 7 (46,XX,inv(7)(p15q21)x2) which was confirmed to be heterozygous in both unaffected parents. Since the resolution of the karyotype was insufficient to identify any putatively causative gene, we undertook medium-coverage whole genome sequencing using paired-end reads, in order to elucidate the molecular breakpoints. In a two-step analysis, we first narrowed down the region by identifying discordant read-pairs, and then determined the precise molecular breakpoint by analysing the mapping locations of "soft-clipped" breakpoint spanning reads. PCR and Sanger sequencing confirmed the identified breakpoints, both of which were located in intergenic regions. Significantly, the 7p15 breakpoint was located 523 kb upstream of HOXA13, the locus for hand-foot-genital syndrome. By inference from studies of HOXA locus control in the mouse, we suggest that the inversion has delocalised a HOXA13 enhancer to produce the phenotype observed in our patient. This study demonstrates how modern genetic diagnostic approach can characterise structural variants at nucleotide resolution and provide potential insights into functional regulation. PMID- 27272186 TI - Maelstrom Research guidelines for rigorous retrospective data harmonization. AB - Background: It is widely accepted and acknowledged that data harmonization is crucial: in its absence, the co-analysis of major tranches of high quality extant data is liable to inefficiency or error. However, despite its widespread practice, no formalized/systematic guidelines exist to ensure high quality retrospective data harmonization. Methods: To better understand real-world harmonization practices and facilitate development of formal guidelines, three interrelated initiatives were undertaken between 2006 and 2015. They included a phone survey with 34 major international research initiatives, a series of workshops with experts, and case studies applying the proposed guidelines. Results: A wide range of projects use retrospective harmonization to support their research activities but even when appropriate approaches are used, the terminologies, procedures, technologies and methods adopted vary markedly. The generic guidelines outlined in this article delineate the essentials required and describe an interdependent step-by-step approach to harmonization: 0) define the research question, objectives and protocol; 1) assemble pre-existing knowledge and select studies; 2) define targeted variables and evaluate harmonization potential; 3) process data; 4) estimate quality of the harmonized dataset(s) generated; and 5) disseminate and preserve final harmonization products. Conclusions: This manuscript provides guidelines aiming to encourage rigorous and effective approaches to harmonization which are comprehensively and transparently documented and straightforward to interpret and implement. This can be seen as a key step towards implementing guiding principles analogous to those that are well recognised as being essential in securing the foundational underpinning of systematic reviews and the meta-analysis of clinical trials. PMID- 27272188 TI - Global transcriptome analysis for identification of interactions between coding and noncoding RNAs during human erythroid differentiation. AB - Studies on coding genes, miRNAs, and lncRNAs during erythroid development have been performed in recent years. However, analysis focusing on the integration of the three RNA types has yet to be done. In the present study, we compared the dynamics of coding genes, miRNA, and lncRNA expression profiles. To explore dynamic changes in erythropoiesis and potential mechanisms that control these changes in the transcriptome level, we took advantage of high throughput sequencing technologies to obtain transcriptome data from cord blood hematopoietic stem cells and the following four erythroid differentiation stages, as well as from mature red blood cells. Results indicated that lncRNAs were promising cell marker candidates for erythroid differentiation. Clustering analysis classified the differentially expressed genes into four subtypes that corresponded to dynamic changes during stemness maintenance, mid-differentiation, and maturation. Integrated analysis revealed that noncoding RNAs potentially participated in controlling blood cell maturation, and especially associated with heme metabolism and responses to oxygen species and DNA damage. These regulatory interactions were displayed in a comprehensive network, thereby inferring correlations between RNAs and their associated functions. These data provided a substantial resource for the study of normal erythropoiesis, which will permit further investigation and understanding of erythroid development and acquired erythroid disorders. PMID- 27272189 TI - Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen positive liver transplant recipients after longterm minimal immunosuppression. AB - Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion +/- detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD. PMID- 27272190 TI - Endovascular Treatment of Renal Artery Stenosis in the Post CORAL Era. AB - OPINION STATEMENT: Atherosclerotic renal artery stenosis (RAS) is highly associated with hypertension and renal insufficiency. Determining causation and who may benefit from RAS treatment remains difficult. The role of endovascular management of atherosclerotic RAS was challenged by several recent randomized controlled trials (RCT) which failed to demonstrate benefit of stenting. In the largest RCT to date, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study did not find benefit of revascularization compared to medical therapy alone. While such RCTs represent the highest level of evidence to date, the conclusions drawn from them should be interpreted with caution due to substantial flaws in study design, inclusion, and exclusion criteria. The current AHA/ACC recommendations for RAS management are supported by many level-II evidence cohort studies which consistently found benefit of revascularization in groups with the highest likelihood of clinically significant RAS. Further study of these patient groups are needed to define a clear role for endovascular therapy of renal artery stenosis. PMID- 27272191 TI - Erratum to: LC-MS/MS Analysis of Cerebrospinal Fluid Metabolites in the Pterin Biosynthetic Pathway. PMID- 27272192 TI - Biological Nitrogen Removal through Nitritation Coupled with Thiosulfate-Driven Denitritation. AB - A novel biological nitrogen removal system based on nitritation coupled with thiosulfate-driven denitritation (Nitritation-TDD) was developed to achieve a high nitrogen removal rate and low sludge production. A nitritation sequential batch reactor (nitritation SBR) and an anoxic up-flow sludge bed (AnUSB) reactor were applied for effective nitritation and denitritation, respectively. Above 75% nitrite was accumulated in the nitritation SBR with an influent ammonia loading rate of 0.43 kg N/d/m(3). During Nitritation-TDD operation, particle sizes (d50) of the sludge decreased from 406 to 225 um in nitritation SBR and from 327-183 um in AnUSB reactor. Pyrosequencing tests revealed that ammonium-oxidizing bacteria (AOB) population was stabilized at approximately 7.0% (calculated as population of AOB-related genus divided by the total microbial population) in the nitritation SBR. In contrast, nitrite-oxidizing bacteria (NOB) population decreased from 6.5-0.6% over the same time, indicating the effective nitrite accumulation in the nitritation SBR. Thiobacillus, accounting for 34.2% in the AnUSB reactor, was mainly responsible for nitrogen removal via autotrophic denitritation, using an external source of thiosulfate as electron donor. Also, it was found that free nitrous acid could directly affect the denitritation activity. PMID- 27272193 TI - Cleidocranial dysplasia and RUNX2-clinical phenotype-genotype correlation. AB - Runt-related transcription factor 2 (RUNX2/Cbfa1) is the main regulatory gene controlling skeletal development and morphogenesis in vertebrates. It is located on chromosome 6p21 and has two functional isoforms (type I and type II) under control of two alternate promoters (P1 and P2). Mutations within RUNX2 are linked to Cleidocranial dysplasia syndrome (CCD) in humans. CCD is an autosomal skeletal disorder characterized by several features such as delayed closure of fontanels, dental abnormalities and hypoplastic clavicles. Here, we summarize recent knowledge about RUNX2 function, mutations and their phenotypic consequences in patients. PMID- 27272194 TI - Antinociceptive effects of dehydrocorydaline in mouse models of inflammatory pain involve the opioid receptor and inflammatory cytokines. AB - Dehydrocorydaline (DHC) is an alkaloidal component isolated from Rhizoma corydalis. Previous studies have shown that DHC has anti-inflammatory and anti tumor effects and that it can protect the cardiovascular system. However, there are few studies of the antinociceptive effects of DHC in vivo. This study explored the antinociceptive effects and possible mechanisms of DHC in mice using two inflammatory pain models: the acetic acid-induced writhing test and the formalin paw test. The intraperitoneal administration of DHC (3.6, 6 or 10 mg/kg) showed a dose-dependent antinociceptive effect in the acetic acid-induced writhing test and significantly attenuated the formalin-induced pain responses in mice. The antinociceptive effects of DHC were not associated with changes in the locomotor activity or motor responses of animals, and no obvious acute or chronic toxic effects were observed in the mice. Furthermore, the use of naloxone confirmed the involvement of the opioid receptor in the central antinociceptive effects of DHC. DHC reduced formalin-induced paw edema, which indicated that DHC may produce an anti-inflammatory effect in the periphery. In the formalin test, DHC decreased the expression of caspase 6 (CASP6), TNF-alpha, IL-1beta and IL-6 proteins in the spinal cord. These findings confirm that DHC has antinociceptive effects in mice. PMID- 27272195 TI - [Diamond-Forrester and cardiac CT : Is there a need to redefine the pretest probability of coronary artery disease?]. AB - Apart from the Diamond-Forrester classification, which is widely used particularly in the USA for the pretest probability of coronary artery disease, other scores also exist, such as an updated version of the classification table by Genders et al., the Morise score and the Duke clinical risk score. These scores estimate the probability of coronary artery disease, defined as the presence of at least one high-grade stenosis, based on symptom characteristics, age, gender and other parameters. All of the scores were derived from patient cohorts in which invasive coronary angiography had been performed for clinical reasons. It has subsequently been shown that these scores, especially those developed several decades ago, substantially overestimate the pretest probability of coronary artery disease. When these risk scores are applied to patients for whom a non-invasive work-up of suspected coronary artery disease is planned, for example by coronary computed tomography (CT) angiography, the expected prevalence of significant coronary stenosis will be overestimated. This, in turn, influences the test characteristics and the significance of the non-invasive examination (positive and negative predictive values) and needs to be taken into account when interpreting test results. PMID- 27272196 TI - Sentence Repetition Accuracy in Adults With Developmental Language Impairment: Interactions of Participant Capacities and Sentence Structures. AB - PURPOSE: We asked whether sentence repetition accuracy could be explained by interactions of participant processing limitations with the structures of the sentences. We also tested a prediction of the procedural deficit hypothesis (Ullman & Pierpont, 2005) that adjuncts are more difficult than arguments for individuals with developmental language impairment (DLI). METHOD: Forty-four young adults participated, 21 with DLI. The sentence repetition task varied sentence length and the use of arguments and adjuncts. We also administered measures of working memory and processing speed. Our regression models focused on these interactions: group and argument status; processing speed, length, and argument status; and working memory capacity, length, and argument status. RESULTS: Language ability group was a significant predictor of sentence repetition accuracy but did not interact with argument status. Processing speed interacted with sentence length and argument status. Working memory capacity and its separate interactions with argument status and sentence length predicted sentence repetition accuracy. CONCLUSIONS: Many adults with DLI may have difficulty with adjuncts as a result of their working memory limitations rather than their language ability. Cognitive limitations common to individuals with DLI are revealed more by particular sentence structures, suggesting ways to construct more diagnostically accurate sentence repetition tasks. PMID- 27272197 TI - A method for the measurement of dispersion curves of circumferential guided waves radiating from curved shells: experimental validation and application to a femoral neck mimicking phantom. AB - Our long-term goal is to develop an ultrasonic method to characterize the thickness, stiffness and porosity of the cortical shell of the femoral neck, which could enhance hip fracture risk prediction. To this purpose, we proposed to adapt a technique based on the measurement of guided waves. We previously evidenced the feasibility of measuring circumferential guided waves in a bone mimicking phantom of a circular cross-section of even thickness. The goal of this study is to investigate the impact of the complex geometry of the femoral neck on the measurement of guided waves. Two phantoms of an elliptical cross-section and one phantom of a realistic cross-section were investigated. A 128-element array was used to record the inter-element response matrix of these waveguides. This experiment was simulated using a custom-made hybrid code. The response matrices were analyzed using a technique based on the physics of wave propagation. This method yields portions of dispersion curves of the waveguides which were compared to reference dispersion curves. For the elliptical phantoms, three portions of dispersion curves were determined with a good agreement between experiment, simulation and theory. The method was thus validated. The characteristic dimensions of the shell were found to influence the identification of the circumferential wave signals. The method was then applied to the signals backscattered by the superior half of constant thickness of the realistic phantom. A cut-off frequency and some portions of modes were measured, with a good agreement with the theoretical curves of a plate waveguide. We also observed that the method cannot be applied directly to the signals backscattered by the lower half of varying thicknesses of the phantom. The proposed approach could then be considered to evaluate the properties of the superior part of the femoral neck, which is known to be a clinically relevant site. PMID- 27272199 TI - Survival after pathogen exposure in group-living insects: don't forget the stress of social isolation! AB - A major cost of group-living is its inherent risk of pathogen infection. To limit this risk, many group-living animals have developed the capability to prophylactically boost their immune system in the presence of group members and/or to mount collective defences against pathogens. These two phenomena, called density-dependent prophylaxis and social immunity, respectively, are often used to explain why, in group-living species, individuals survive better in groups than in isolation. However, this survival difference may also reflect an alternative and often overlooked process: a cost of social isolation on individuals' capability to fight against infections. Here, we disentangled the effects of density-dependent prophylaxis, social immunity and stress of social isolation on the survival after pathogen exposure in group-living adults of the European earwig Forficula auricularia. By manipulating the presence of group members both before and after pathogen exposure, we demonstrated that the cost of being isolated after infection, but not the benefits of social immunity or density-dependent prophylaxis, explained the survival of females. Specifically, females kept constantly in groups or constantly isolated had higher survival rates than females that were first in groups and then isolated after infection. Our results also showed that this cost of social isolation was absent in males and that social isolation did not reduce the survival of noninfected individuals. Overall, this study gives a new perspective on the role of pathogens in social evolution, as it suggests that an apparently nonadaptive, personal immune process may promote the maintenance of group-living under pathogenic environments. PMID- 27272200 TI - Impact of intraprosthetic drilling on the strength of the femoral stem in periprosthetic fractures: A finite element investigation. AB - Treatment of periprosthetic femur fractures after total hip arthroplasty remains a major challenge in orthopedic surgery. Recently, a novel surgical technique using intraprosthetic screw fixation has been suggested. The purpose of this study was to evaluate the influence of drilling the femoral hip stem on integrity and strength of the implant. The hypothesis was that intraprosthetic drilling and screw fixation would not cause the load limit of the prosthesis to be exceeded and that deformation would remain within the elastic limit. A sawbone model with a conventional straight hip stem was used and a Vancouver C periprosthetic fracture was created. The fracture was fixed with a nine-hole less invasive stabilization system plate with two screws drilled and inserted through the femoral hip stem. Three different finite element models were created using ANSYS software. The models increased in complexity including joint forces and stress risers from three different dimensions. A variation of drilling positions was analyzed. Due to the complexity of the physiological conditions in the human femur, the most complex finite element model provided the most realistic results. Overall, significant changes in the stresses to the prosthesis caused by the drilling procedure were observed. While the stresses at the site of the bore hole decreased, the load increased in the surrounding stem material. This effect is more pronounced and further the holes were apart, and it was found that increasing the number of holes could counteract this. The maximum load was still found to be in the area of the prosthesis neck. No stresses above the load limit of titanium alloy were detected. All deformations of the prosthesis stem remained in the elastic range. These results may indicate a potential role for intraprosthetic screw fixation in the future treatment of periprosthetic femur fractures. PMID- 27272201 TI - Symmetry comparison between sacrum and center of mass during walking. AB - Sacrum motion is used extensively in clinical research to represent movement of the entire body by replacing the center of mass. The primary objective of this article was to investigate the effect of this replacement on symmetry determination. The secondary objective was to assess the correlation between the symmetries of trajectories of center of mass and sacrum, and that of spatiotemporal parameters. Three-dimensional trajectories obtained from 37 markers placed on anatomical landmarks of 15 healthy subjects were recorded while walking at three speeds on the treadmill. Trajectory of center of mass was determined using segmental analysis method. The results indicated that two symmetries, one determined using sacrum marker and the other using segmental analysis method, were different and this difference was more pronounced in anterior-posterior direction. In other words, harmonic analysis of sacrum and center of mass trajectories revealed different results. Furthermore, low-to moderate correlations were observed between spatiotemporal parameters symmetry and symmetries obtained from both center of mass and sacrum. In conclusion, the results indicated that it may not be analytically acceptable to substitute sacrum for center of mass in symmetry determination. PMID- 27272198 TI - Task-irrelevant fear enhances amygdala-FFG inhibition and decreases subsequent face processing. AB - Facial threat is associated with changes in limbic activity as well as modifications in the cortical face-related N170. It remains unclear if task irrelevant threat modulates the response to a subsequent facial stimulus, and whether the amygdala's role in early threat perception is independent and direct, or modulatory. In 19 participants, crowds of emotional faces were followed by target faces and a rating task while simultaneous EEG-fMRI were recorded. In addition to conventional analyses, fMRI-informed EEG analyses and fMRI dynamic causal modeling (DCM) were performed. Fearful crowds reduced EEG N170 target face amplitudes and increased responses in a fMRI network comprising insula, amygdala and inferior frontal cortex. Multimodal analyses showed that amygdala response was present ~60 ms before the right fusiform gyrus-derived N170. DCM indicated inhibitory connections from amygdala to fusiform gyrus, strengthened when fearful crowds preceded a target face. Results demonstrated the suppressing influence of task-irrelevant fearful crowds on subsequent face processing. The amygdala may be sensitive to task-irrelevant fearful crowds and subsequently strengthen its inhibitory influence on face-responsive fusiform N170 generators. This provides spatiotemporal evidence for a feedback mechanism of the amygdala by narrowing attention in order to focus on potential threats. PMID- 27272202 TI - Inflammation-induced transgene expression in genetically engineered equine mesenchymal stem cells. AB - BACKGROUND: Osteoarthritis, a chronic and progressive degenerative joint disorder, ranks amongst the top five causes of disability. Given the high incidence, associated socioeconomic costs and the absence of effective disease modifying therapies of osteoarthritis, cell-based treatments offer a promising new approach. Owing to their paracrine, differentiation and self-renewal abilities, mesenchymal stem cells (MSCs) have great potential for regenerative medicine, which might be further enhanced by targeted gene therapy. Hence, the development of systems allowing transgene expression, particularly when regulated by natural disease-dependent occuring substances, is of high interest. METHODS: Bone marrow-isolated equine MSCs were stably transduced with an HIV-1 based lentiviral vector expressing the luciferase gene under control of an inducible nuclear factor kappaB (NFkappaB)-responsive promoter. Marker gene expression was analysed by determining luciferase activity in transduced cells stimulated with different concentrations of interleukin (IL)-1beta or tumour necrosis factor (TNF)alpha. RESULTS: A dose-dependent increase in luciferase expression was observed in transduced MSCs upon cytokine stimulation. The induction effect was more potent in cells treated with TNFalpha compared to those treated with IL 1beta. Maximum transgene expression was obtained after 48 h of stimulation and the same time was necessary to return to baseline luciferase expression levels after withdrawal of the stimulus. Repeated cycles of induction allowed on-off modulation of transgene expression without becoming refractory to induction. The NFkappaB-responsive promoter retained its inducibility also in chondrogenically differentiated MSC/Luc cells. CONCLUSIONS: The results of the present study demonstrate that on demand transgene expression from the NFkappaB-responsive promoter using naturally occurring inflammatory cytokines can be induced in undifferentiated and chondrogenically differentiated equine MSCs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27272203 TI - Impact of body mass index on the oncological outcomes of patients treated with radical cystectomy for muscle-invasive bladder cancer. AB - PURPOSE: Body mass index (BMI) has been associated with worse outcomes in several solid malignancies. We aimed to evaluate the association between BMI and oncological outcomes in patients treated with radical cystectomy (RC) for muscle invasive urothelial carcinoma of the bladder (UCB). METHODS: We retrospectively reviewed 701 consecutive patients treated with RC and pelvic lymphadenectomy for UCB at our institution between 1995 and 2011. Univariable and multivariable Cox regression models investigated the association of BMI with disease recurrence and cancer-specific mortality. BMI was analyzed as both continuous and categorical variable (<25 vs. 25-29 vs. >=30 kg/m2). RESULTS: From the 701 patients, 275 (39.2 %) had a BMI < 25 kg/m2, 280 (39.9 %) had a BMI between 25 and 29.9 kg/m2, and 146 (20.9 %) had a BMI ? 30 kg/m2. Within a median follow-up of 45 months (IQR 23-75), 163 patients (23.3 %) experienced a disease recurrence and 127 (18.1 %) died from the disease. In univariable analyses, BMI ? 30 kg/m2 was associated with a higher risk of disease recurrence and cancer-specific mortality (both p values <0.01). In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI ? 30 kg/m2 was associated with both higher risks of disease recurrence (HR 1.58; 95 % CI 1.06-2.34, p = 0.02) and cancer-specific mortality (HR 1.58; 95 % CI 1.01-2.48; p = 0.04). CONCLUSIONS: Obesity was independently associated with higher risks of disease recurrence and cancer-specific mortality in patients treated with RC for muscle-invasive UCB. BMI is a modifiable feature that may have significant individual and public health implications in patients with muscle-invasive UCB. PMID- 27272204 TI - Unforeseen Severe Cardiotoxicity Associated With Daunorubicin Chemotherapy Even at a Dose Previously Thought to Be Safe: A Case Report. PMID- 27272205 TI - The evolution of genome mining in microbes - a review. AB - Covering: 2006 to 2016The computational mining of genomes has become an important part in the discovery of novel natural products as drug leads. Thousands of bacterial genome sequences are publically available these days containing an even larger number and diversity of secondary metabolite gene clusters that await linkage to their encoded natural products. With the development of high throughput sequencing methods and the wealth of DNA data available, a variety of genome mining methods and tools have been developed to guide discovery and characterisation of these compounds. This article reviews the development of these computational approaches during the last decade and shows how the revolution of next generation sequencing methods has led to an evolution of various genome mining approaches, techniques and tools. After a short introduction and brief overview of important milestones, this article will focus on the different approaches of mining genomes for secondary metabolites, from detecting biosynthetic genes to resistance based methods and "evo-mining" strategies including a short evaluation of the impact of the development of genome mining methods and tools on the field of natural products and microbial ecology. PMID- 27272206 TI - Highly sensitive colorimetric detection of glucose and uric acid in biological fluids using chitosan-modified paper microfluidic devices. AB - This paper describes the modification of microfluidic paper-based analytical devices (MUPADs) with chitosan to improve the analytical performance of colorimetric measurements associated with enzymatic bioassays. Chitosan is a natural biopolymer extensively used to modify biosensing surfaces due to its capability of providing a suitable microenvironment for the direct electron transfer between an enzyme and a reactive surface. This hypothesis was investigated using glucose and uric acid (UA) colorimetric assays as model systems. The best colorimetric sensitivity for glucose and UA was achieved using a chromogenic solution composed of 4-aminoantipyrine and sodium 3,5-dichloro-2 hydroxy-benzenesulfonate (4-AAP/DHBS), which provided a linear response for a concentration range between 0.1 and 1.0 mM. Glucose and UA were successfully determined in artificial serum samples with accuracies between 87 and 114%. The limits of detection (LODs) found for glucose and UA assays were 23 and 37 MUM, respectively. The enhanced analytical performance of chitosan-modified MUPADs allowed the colorimetric detection of glucose in tear samples from four nondiabetic patients. The achieved concentration levels ranged from 130 to 380 MUM. The modified MUPADs offered analytical reliability and accuracy as well as no statistical difference from the values achieved through a reference method. Based on the presented results, the proposed MUPAD can be a powerful alternative tool for non-invasive glucose analysis. PMID- 27272208 TI - Efficacy of XP-endo finisher files in the removal of calcium hydroxide paste from artificial standardized grooves in the apical third of oval root canals. AB - AIM: To compare the efficacy of the XP-endo finisher file (XP) (FKG Dentaire, La Chaux de Fonds, Switzerland) to that of passive ultrasonic irrigation (PUI) and conventional syringe and needle irrigation (SNI) in the removal of calcium hydroxide paste from an artificial standardized groove in the apical third of root canals. METHODOLOGY: The root canals of 68 mandibular incisors with single oval canals were prepared using Mtwo instruments (VDW GmbH, Munich, Germany) up to size 40, .04 taper. Each tooth was split longitudinally, and in one half of the root, a standardized groove was prepared in the apical part of the specimen. The grooves were filled with Ca(OH)2 , and the root halves were reassembled. The roots were randomly divided into two control groups (n = 4) and three experimental groups (n = 20) according to the Ca(OH)2 methods used: XP, PUI and SNI. The amount of remaining medicament was evaluated under X25 magnification using a 4-grade scoring system. Kappa values were calculated for intra- and interobserver agreement evaluation. The differences in the Ca(OH)2 scores amongst the different groups were analysed using the Kruskal-Wallis test. RESULTS: None of the tested methods could completely clean the Ca(OH)2 from the artificial standardized groove in the apical third of the root canals. XP and PUI removed significantly more Ca(OH)2 than SNI (P < 0.001), with no significant differences between them (P = 0.238). CONCLUSIONS: XP and PUI were more effective in removing Ca(OH)2 from artificial standardized grooves in the apical third of root canals than SNI. PMID- 27272207 TI - Analysis of the Microprocessor in Dictyostelium: The Role of RbdB, a dsRNA Binding Protein. AB - We identified the dsRNA binding protein RbdB as an essential component in miRNA processing in Dictyostelium discoideum. RbdB is a nuclear protein that accumulates, together with Dicer B, in nucleolar foci reminiscent of plant dicing bodies. Disruption of rbdB results in loss of miRNAs and accumulation of primary miRNAs. The phenotype can be rescued by ectopic expression of RbdB thus allowing for a detailed analysis of domain function. The lack of cytoplasmic dsRBD proteins involved in miRNA processing, suggests that both processing steps take place in the nucleus thus resembling the plant pathway. However, we also find features e.g. in the domain structure of Dicer which suggest similarities to animals. Reduction of miRNAs in the rbdB- strain and their increase in the Argonaute A knock out allowed the definition of new miRNAs one of which appears to belong to a new non-canonical class. PMID- 27272209 TI - Pollen limitation may be a common Allee effect in marine hydrophilous plants: implications for decline and recovery in seagrasses. AB - Pollen limitation may be an important factor in accelerated decline of sparse or fragmented populations. Little is known whether hydrophilous plants (pollen transport by water) suffer from an Allee effect due to pollen limitation or not. Hydrophilous pollination is a typical trait of marine angiosperms or seagrasses. Although seagrass flowers usually have high pollen production, floral densities are highly variable. We evaluated pollen limitation for intertidal populations of the seagrass Zostera noltei in The Netherlands and found a significant positive relation between flowering spathe density and fruit-set, which was suboptimal at <1200 flowering spathes m(-2) (corresponding to <600 reproductive shoots m(-2)). A fragmented population had ~35 % lower fruit-set at similar reproductive density than a continuous population. 75 % of all European populations studied over a large latitudinal gradient had flowering spathe densities below that required for optimal fruit-set, particularly in Southern countries. Literature review of the reproductive output of hydrophilous pollinated plants revealed that seed- or fruit-set of marine hydrophilous plants is generally low, as compared to hydrophilous freshwater and wind-pollinated plants. We conclude that pollen limitation as found in Z. noltei may be a common Allee effect for seagrasses, potentially accelerating decline and impairing recovery even after environmental conditions have improved substantially. PMID- 27272210 TI - 3D Printed Vascular Networks Enhance Viability in High-Volume Perfusion Bioreactor. AB - There is a significant clinical need for engineered bone graft substitutes that can quickly, effectively, and safely repair large segmental bone defects. One emerging field of interest involves the growth of engineered bone tissue in vitro within bioreactors, the most promising of which are perfusion bioreactors. Using bioreactor systems, tissue engineered bone constructs can be fabricated in vitro. However, these engineered constructs lack inherent vasculature and once implanted, quickly develop a necrotic core, where no nutrient exchange occurs. Here, we utilized COMSOL modeling to predict oxygen diffusion gradients throughout aggregated alginate constructs, which allowed for the computer-aided design of printable vascular networks, compatible with any large tissue engineered construct cultured in a perfusion bioreactor. We investigated the effect of 3D printed macroscale vascular networks with various porosities on the viability of human mesenchymal stem cells in vitro, using both gas-permeable, and non-gas permeable bioreactor growth chamber walls. Through the use of 3D printed vascular structures in conjunction with a tubular perfusion system bioreactor, cell viability was found to increase by as much as 50% in the core of these constructs, with in silico modeling predicting construct viability at steady state. PMID- 27272211 TI - The Importance of Hemorheology and Patient Anatomy on the Hemodynamics in the Inferior Vena Cava. AB - Inferior vena cava (IVC) filters have been used for nearly half a century to prevent pulmonary embolism in at-risk patients. However, complications with IVC filters remain common. In this study, we investigate the importance of considering the hemorheological and morphological effects on IVC hemodynamics by simulating Newtonian and non-Newtonian blood flow in three IVC models with varying levels of geometric idealization. Partial occlusion by an IVC filter and a thrombus is also considered. More than 99% of the infrarenal IVC volume is found to contain flow in the nonlinear region of the shear rate-viscosity curve for blood (less than 100 s-1) in the unoccluded IVCs. Newtonian simulations performed using the asymptotic viscosity for blood over-predict the non-Newtonian Reynolds numbers by more than a factor of two and under-predict the mean wall shear stress (WSS) by 28-54%. Agreement with the non-Newtonian simulations is better using a characteristic viscosity, but local WSS errors are still large (up to 50%) in the partially occluded cases. Secondary flow patterns in the IVC also depend on the viscosity model and IVC morphological complexity. Non-Newtonian simulations required only a marginal increase in computational expense compared with the Newtonian simulations. We recommend that future studies of IVC hemodynamics consider the effects of hemorheology and IVC morphology when accurate predictions of WSS and secondary flow features are desired. PMID- 27272212 TI - Recent advances in preimplantation genetic diagnosis and screening. AB - Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics. PMID- 27272213 TI - Hepatitis B and Schistosoma co-infection in a non-endemic area. AB - Schistosomiasis is related to the development of liver fibrosis and portal hypertension. Chronic co-infection with HBV and Schistosoma has been associated in endemic areas with a higher risk for a more severe liver disease. However, no studies have assessed the real importance of this co-infection in non-endemic regions. This is a retrospective observational study of Sub-Saharan immigrants attending between October 2004 and February 2014. Patients with chronic HBV infection with and without evidence of schistosomal infection were compared. Epidemiological, analytical, and microbiological data were analysed. Likelihood of liver fibrosis based on APRI and FIB-4 indexes was established. A total of 507 patients were included in the study, 170 (33.5 %) of them harbouring evidence of schistosome infection. No differences were found in transaminase, GGT, and ALP levels. In fibrosis tests, a higher proportion of patients with HVB and S. mansoni detection reached possible fibrosis scores (F > 2) when compared to patients without schistosomiasis: 17.4 vs 14.2 % and 4.3 % vs 4.2 % (using high sensitivity and high specificity cut-offs respectively), although differences were not statistically significant (p = 0.69, p = 0.96). For possible cirrhosis (F4) score, similar results were observed: 4.3 % of co-infected patients vs 2.1 % of mono-infected ones, p = 0.46. According to these datas, in non-endemic regions the degree of hepatic fibrosis in patients with chronic hepatitis B is not substantially modified by schistosome co-infection. PMID- 27272214 TI - Long noncoding RNA PVT1 promotes cervical cancer progression through epigenetically silencing miR-200b. AB - Long noncoding RNA PVT1 has been reported to be dysregulated and play vital roles in a variety of cancers. However, the functions and molecular mechanisms of PVT1 in cervical cancer remain unclear. The objective of this study was to investigate the expression, clinical significance, biological roles, and underlying functional mechanisms of PVT1 in cervical cancer. Our results revealed that PVT1 is upregulated in cervical cancer tissues. Enhanced expression of PVT1 is associated with larger tumor size, advanced International Federation of Gynecology and Obstetrics stage, and poor prognosis of cervical cancer patients. Using gain-of-function and loss-of-function approaches, we demonstrated that overexpression of PVT1 promotes cervical cancer cells proliferation, cell cycle progression and migration, and depletion of PVT1 inhibits cervical cancer cell proliferation, cell cycle progression, and migration. Mechanistically, we verified that PVT1 binds to EZH2, recruits EZH2 to the miR-200b promoter, increases histone H3K27 trimethylation level on the miR-200b promoter, and inhibits miR-200b expression. Furthermore, the effects of PVT1 on cervical cell proliferation and migration depend upon silencing of miR-200b. Taken together, our findings confirmed that PVT1 functions as an oncogene in cervical cancer and indicated that PVT1 is not only an important prognostic marker, but also a potential therapy target for cervical cancer. PMID- 27272215 TI - On Making Statistical Inferences Regarding the Relationship between Spawners and Recruits and the Irresolute Case of Western Atlantic Bluefin Tuna (Thunnus thynnus). AB - Forecasts of the future abundance of western Atlantic bluefin tuna (Thunnus thynnus) have, for nearly two decades, been based on two competing views of future recruitment potential: (1) a "low" recruitment scenario based on hockey stick (two-line) curve where the expected level of recruitment is set equal to the geometric mean of the recruitment estimates for the years after a supposed regime-shift in 1975, and (2) a "high" recruitment scenario based on a Beverton Holt curve fit to the time series of spawner-recruit pairs beginning in 1970. Several investigators inferred the relative plausibility of these two scenarios based on measures of their ability to fit estimates of spawning biomass and recruitment derived from stock assessment outputs. Typically, these comparisons have assumed the assessment estimates of spawning biomass are known without error. It is shown here that ignoring error in the spawning biomass estimates can predispose model-choice approaches to favor the regime-shift hypothesis over the Beverton-Holt curve with higher recruitment potential. When the variance of the observation error approaches that which is typically estimated for assessment outputs, the same model-choice approaches tend to favor the single Beverton-Holt curve. For this and other reasons, it is argued that standard model-choice approaches are insufficient to make the case for a regime shift in the recruitment dynamics of western Atlantic bluefin tuna. A more fruitful course of action may be to move away from the current high/low recruitment dichotomy and focus instead on adopting biological reference points and management procedures that are robust to these and other sources of uncertainty. PMID- 27272217 TI - Is a Fixed Hybrid Prosthesis with Distal Cantilever Appropriate for Maxillofacial Defects? A Report of Two Patients. AB - The most important objectives in restoring the maxillofacial patient are the restoration of function and psychological improvement through esthetics. Acquired maxillary and mandibular defects due to significant trauma or surgery represent a major challenge for the clinician and patient. Dental implant-retained prostheses represent a well-documented and reliable treatment option and can also help patients with maxillofacial defects by eliminating denture instability and improving function. Full-arch fixed dental hybrid prostheses provide functional and psychological advantages and also reduce the load on vulnerable soft and hard tissues in the reconstruction area. Two clinical reports are presented describing the prosthetic rehabilitation using dental implant-supported fixed hybrid prostheses with clinical and radiographic follow-up of 3 years. PMID- 27272216 TI - Association of CpG island methylator phenotype and EREG/AREG methylation and expression in colorectal cancer. AB - BACKGROUND: High EREG and AREG expression, and left-sided primary tumours are associated with superior efficacy of anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (CRC), but a unifying explanation of these findings is lacking. METHODS: RNA-seq, gene expression arrays, and DNA methylation profiling were completed on 179 CRC tumours. Results were validated using independent The Cancer Genome Atlas data sets. An independent cohort of 198 KRAS wild-type metastatic CRC tumours was tested for CpG island methylator phenotype (CIMP) status, and progression-free survival (PFS) with the first anti EGFR regimen was retrospectively determined. RESULTS: EREG and AREG expression was highly inversely correlated with methylation and was inversely associated with right-sided primary tumour, BRAF mutation, and CIMP-high status. Treatment of CRC cell lines with hypomethylating agents decreased methylation and increased expression of EREG. Inferior PFS with anti-EGFR therapy was associated with CIMP high status, BRAF mutation, NRAS mutation, and right-sided primary tumour on univariate analysis. Among known BRAF/NRAS wild-type tumours, inferior PFS remained associated with CIMP-high status (median PFS 5.6 vs 9.0 mo, P=0.023). CONCLUSIONS: EREG and AREG are strongly regulated by methylation, and their expression is associated with CIMP status and primary tumour site, which may explain the association of primary tumour site and EREG/AREG expression with anti EGFR therapy efficacy. PMID- 27272218 TI - The Trend of Age-Group Effect on Prognosis in Differentiated Thyroid Cancer. AB - Age has been included in various prognostic scoring systems for differentiated thyroid cancer (DTC). The aim of this study is to re-examine the relationship between age and prognosis by using Surveillance, Epidemiology, and End Results (SEER) population-based database. We identified 51,061 DTC patients between 2004 and 2012. Patients were separated into 10-year age groups. Cancer cause-specific survival (CSS) and overall survival (OS) data were obtained. Kaplan-Meier and multivariable Cox models were built to analyze the outcomes and risk factors. Increasing age gradient with a 10-year interval was associated with the trend of higher proportions for male gender, grade III/IV and summary stage of distant metastases. Both CSS and OS continued to worsen with increasing age, being poorest in in the oldest age group (>=71); multivariate analysis confirmed that CSS continued to fall with each age decade, significantly starting at 60 years (HR = 7.5, 95% 1.0-54.1, p = 0.047) compared to the young group (<=20). Similarly, multivariate analysis suggested that OS continued worsening with increasing age, but starting at 40 years (HR = 3.7, 95% 1.4-10.1, p = 0.009) compared to the young group. The current study suggests that an age exceeding 60 years itself represents an unfavorable prognostic factor and high risk for cancer specific death in DTC. PMID- 27272219 TI - How long may a breath sample be stored for at -80 degrees C? A study of the stability of volatile organic compounds trapped onto a mixed Tenax:Carbograph trap adsorbent bed from exhaled breath. AB - Thermal desorption is used extensively in exhaled breath volatile organic compound (VOC) analysis, and it is often necessary to store the adsorbent tube samples before analysis. The possible introduction of storage artefacts is an important potential confounding factor in the development of standard methodologies for breath sampling and analysis. The stability of VOCs trapped from breath samples onto a dual bed Tenax((r)) TA:Carbograph adsorbent tube and stored -80 degrees C was studied over 12.5 month. 25 samples were collected from a single male participant over 3 h and then stored at -80 degrees C. Randomly selected adsorbent tubes were subsequent analysed by thermal desorption-gas chromatography-mass spectrometry at 5 times points throughout the 12.5 month of the study. Toluene-d8, decane-d22 and hexadecane-d34 internal standards were used to manage the instrument variability throughout the duration of the study. A breath-matrix consisting of 161 endogenous and 423 exogenous VOC was created. Iterative orthogonal partial least squared discriminant analysis (OPLS-DA) and principal components analysis (PCA) indicated that it was not possible to detect storage artefacts at 1.5 month storage. By 6 month storage artefacts were discernible with significant changes observed for 27% of the recovered VOC. Endogenous VOC were observed to be more susceptible to storage. A paired two tailed t-test on the endogenous compounds indicated that the maximum storage duration under these conditions was 1.5 month with 94% of the VOCs stable. This study indicates that a prudent approach is best adopted for the storage of adsorbent samples; storage times should be minimised, and storage time examined as a possible discriminatory factor in multivariate analysis. PMID- 27272220 TI - Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect. AB - Combating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced. Sulfonylurea category of anti diabetic drug often suffers from cross reactivity with sulfamethoxazole (SMX), a common drug in use to treat a handful of microbial infections. However the specific cellular target generating postprandial hypoglycemia on SMX administration is till date unraveled. The present work has been initiated to elucidate the effects of a group of sulfonamide drugs inclusive of SMX for their amylase inhibitory role. SMX inhibits porcine pancreatic amylase (PPA) in a noncompetitive mode with an average IC50 value 0.94 mM respectively. Interaction of SMX with PPA is manifested with gradual quenching of tryptophan fluorescence with concomitant shift in lambda max value (lambdamax). Binding is governed by entropy driven factor (24.8 cal mol(-1) K(-1)) with unfavorable contribution from enthalpy change. SMX interferes with the activity of acarbose in a synergistic mode to reduce the effective dose of acarbose as evident from the in vitro PPA inhibition study. In summary, loss of PPA activity in presence of SMX is indicative of structural changes of PPA which is further augmented in the presence of acarbose as explained in the schematic model and docking study. PMID- 27272221 TI - Antioxidant Properties and Gastroprotective Effects of 2 (Ethylthio)Benzohydrazones on Ethanol-Induced Acute Gastric Mucosal Lesions in Rats. AB - A series of new 2-(ethylthio)benzohydrazone derivatives (1-6) were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up regulation of HSP70 and down-regulation of Bax protein in stained tissue section. PMID- 27272223 TI - Quantification of vaginal atrophy: several decades of advances. PMID- 27272222 TI - Structural, electronic and kinetic properties of the phase-change material Ge2Sb2Te5 in the liquid state. AB - Phase-change materials exhibit fast and reversible transitions between an amorphous and a crystalline state at high temperature. The two states display resistivity contrast, which is exploited in phase-change memory devices. The technologically most important family of phase-change materials consists of Ge-Sb Te alloys. In this work, we investigate the structural, electronic and kinetic properties of liquid Ge2Sb2Te5 as a function of temperature by a combined experimental and computational approach. Understanding the properties of this phase is important to clarify the amorphization and crystallization processes. We show that the structural properties of the models obtained from ab initio and reverse Monte Carlo simulations are in good agreement with neutron and X-ray diffraction experiments. We extract the kinetic coefficients from the molecular dynamics trajectories and determine the activation energy for viscosity. The obtained value is shown to be fully compatible with our viscosity measurements. PMID- 27272224 TI - The prevalence of endometrial cancer in pre- and postmenopausal Chinese women. AB - OBJECTIVE: The incidence of endometrial cancer depends in part on the ethnicity and geographical area in which the woman resides. Menopause status is a well known risk factor for endometrial cancer and most cases occur after menopause. It is, however, less clear how the menopause status is associated with endometrial cancer including its subtypes in Chinese women. METHODS: Data on 1,746 women with endometrial cancer including age at diagnosis, age at menopause, and tumor histology from two large obstetrical and gynecological hospitals in China were analyzed. RESULTS: The median age of women at diagnosis was 50 years. Fifty-eight percent of women were diagnosed after menopause. Fifty-six percent of women with type 1 and 69% with type 2 were diagnosed after menopause. In addition, in both pre- and postmenopausal women, there was no difference in the age at diagnosis between type 1 (46 vs 46 y) and type 2 endometrial cancer (53 vs 52 y). CONCLUSIONS: Our data demonstrate that although both type 1 and type 2 endometrial cancers are more likely to occur in Chinese women after menopause than before, the total prevalence of endometrial cancer is lower in our study population than in previous reports from white women (80%). The age at diagnosis did not differ between type 1 and type 2 endometrial cancers regardless of the menopause status in our study population. Our results caution clinicians to be more aware of the importance of abnormal uterine bleeding in premenopausal Chinese women. PMID- 27272225 TI - How does adjuvant chemotherapy affect menopausal symptoms, sexual function, and quality of life after breast cancer? AB - OBJECTIVE: The aim of the study was to determine the association between adjuvant chemotherapy for breast cancer and menopausal symptoms, sexual function, and quality of life. METHODS: Participants attended a menopause clinic with a dedicated service for cancer survivors at a large tertiary women's hospital. Information about breast cancer treatments including adjuvant chemotherapy was collected from medical records. Menopausal symptoms were recorded with the Greene Climacteric Scale and Functional Assessment of Cancer Therapy, Breast Cancer, and Endocrine Symptom Subscales. Sexual symptoms were recorded using Fallowfield's Sexual Activity Questionnaire. Quality of life was measured with Functional Assessment of Cancer Therapy scales. RESULTS: The severity of vasomotor, psychological, or sexual symptoms (apart from pain) did not differ between those who had received adjuvant chemotherapy (n = 339) and other breast cancer survivors (n = 465). After adjustment for current age, time since menopause, and current use of antiestrogen endocrine therapy, the risk of "severe pain" with sexual intercourse was twice as common after chemotherapy (31.6% vs 20.0%, odds ratio [OR] 2.18, 95% CI 1.25-3.79). Those treated with chemotherapy were more likely to report "severe problems" with physical well-being (OR 1.92, 95% CI 1.12 3.28) and lower breast cancer-specific quality of life (OR 1.89 95% CI 1.13 3.18), but did not differ in other quality of life measures. CONCLUSIONS: In this large study of breast cancer patients presenting to a specialty menopause clinic, previous chemotherapy was not associated with current vasomotor or psychological symptoms. Severe pain with intercourse was significantly more common in those treated with adjuvant chemotherapy. PMID- 27272226 TI - Cognition and the menopause transition. AB - Complaints about forgetfulness, "brain fog," and difficulty concentrating are common in women transitioning through menopause. Women with these cognitive complaints often express concern about whether these problems are normal, related to menopause, or represent a symptom of Alzheimer disease or another serious cognitive disorder. In this Practice Pearl, we provide a brief summary of the scientific literature on the frequency of cognitive complaints in midlife women, the validity of complaints in relation to performance on standardized cognitive tests, and the influence of menopause on cognitive performance. We then offer recommendations for healthcare providers and women to address cognitive concerns. PMID- 27272228 TI - Media and education of the consumer. AB - The landscape has changed in how consumers get their health information. A shift to the Internet and social media are now the way many consumers obtain their health and medical information. In addition, the highly complex information in medicine and science separates health journalism from other forms of journalism. In this article, the question of the role of media in educating consumers is examined. It is clear that knowledge translation is complex and begs the cooperation of scientists and journalists alike. PMID- 27272227 TI - Symptoms and effects of physical factors in Japanese middle-aged women. AB - OBJECTIVE: The aim of the study was to clarify the prevalence and severity rates of symptoms and investigate whether symptoms varied in relation to body mass index (BMI). METHODS: The study group composed of 1,969 women, aged 40 to 60 years, who presented at our department from 1993 through 2014. The participation rate was 98%. The presence or absence of symptoms was evaluated by having the participants complete the Keio Questionnaire, a self-administered questionnaire. To allow the results to be compared according to ovarian function, serum levels of follicle-stimulating hormone and estradiol were measured. Participants were classified into three groups according to BMI: underweight, normal weight, and overweight. Symptoms were also compared among these subgroups. RESULTS: The most common symptom was general fatigue. Vasomotor symptoms differed significantly between pre- and postmenopause status. When symptoms were analyzed according to BMI, the severity rates of the following symptoms were significantly higher in the overweight group than in the normal weight and underweight groups: hot flushes, sweats, joint pain, numbness, and incontinence. On the contrary, the underweight group had significantly higher severities of cold constitution, nervousness, and wrinkled skin than did the other groups. In addition, an increase in BMI was associated with an increased severity of vasomotor symptoms. CONCLUSIONS: The prevalence and severities of shoulder stiffness, considered a characteristic symptom in Japanese women, were high. Increased BMI was shown to be associated with a higher severity of vasomotor symptoms, joint pain, nervousness, and urinary symptoms. PMID- 27272230 TI - What is this image? 2016: Image 2. PMID- 27272229 TI - Association Between P2RX7 Gene and Hepatocellular Carcinoma Susceptibility: A Case-Control Study in a Chinese Han Population. AB - BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer. It is hypothesized that P2RX7 genetic polymorphisms have strong association with HCC susceptibility. Therefore, a case-control study was designed and performed to verify the association between P2RX7 gene polymorphisms and HCC susceptibility. MATERIAL AND METHODS A total of 646 subjects were recruited in our study, including 323 HCC patients and 323 healthy controls. Five gene polymorphisms, -762C>T (rs2393799), 946G>A (rs28360457), 1513A>C (rs3751143), 1068G>A (rs1718119), and 1096C>G (rs2230911), were selected. Odds ratio (ORs) and 95% confidence interval (CI) were used to quantify the association between P2RX7 gene polymorphisms and the susceptibility to HCC. All tests were performed using SPSS 20 and a 2-sided P value of less than 0.05 was considered to be statistically significant. RESULTS Our results suggest that allelic frequencies of these 5 SNPs all conformed to Hardy-Weinberg equilibrium (HWE). There was no significant difference in genotype and allele distributions of -762C>T and 1096C>G between the case group and the control group. However, an increased risk of HCC was associated with 946G>A (A vs. G: OR=1.48, 95%CI=1.09-2.01, P=0.013; GA+AA vs. GG: OR=1.46, 95%CI=1.03-2.07, P=0.033). A similar increased risk was associated with 1513A>C polymorphism (C vs. A: OR=1.37, 95%CI=1.05-1.79, P=0.021; AC+CC vs. AA: OR=1.40, 95%CI=1.01-1.93, P=0.041). On the other hand, a decreased risk of HCC was associated with gene polymorphism of 1068G>A (A vs. G: OR=0.68, 95%CI=0.51-0.91, P=0.010; GA+AA vs. GG: OR=0.68, 95%CI=0.49-0.96, P=0.027; AA vs. GG: OR=0.42, 95%CI=0.18-0.99, P=0.048). CONCLUSIONS Our results suggest that 3 of the 5 polymorphisms of P2RX7 described above (1513A>C, 946G>A, and 1068G>A) are significantly associated with HCC susceptibility in a Chinese Han population. Studies with larger sample sizes are recommended to confirm whether our results will be applicable to different ethnic populations in China. PMID- 27272231 TI - So We May Not Forget! PMID- 27272232 TI - Nuclear Cardiology in the Literature: A selection of recent, original research papers. PMID- 27272233 TI - Nuclear cardiology and CVD in the developing world: Are we applying our scarce resources appropriately? Why is our mortality rate so high? AB - While mortality rates from cardiovascular diseases have progressively decreased in developed nations, this has not been observed to the same extent in the developing world. Nuclear Cardiology utilization remains low or non-existent for most of those living in the low-to-middle-income countries. How much of the decline in mortality observed in the developed world has to do with advanced cardiac imaging? Are we applying our scarce resources appropriately for myocardial perfusion imaging? Are myocardial revascularizations being guided by appropriate use criteria? Is more imaging necessary to reduce the mortality rates further in the developing world? PMID- 27272234 TI - ISCHEMIA, to revascularize or not to revascularize. PMID- 27272235 TI - Abnormal heart rate response with vasodilator stress myocardial perfusion imaging: Relevance to clinical practice. PMID- 27272236 TI - Network representation of protein interactions: Theory of graph description and analysis. AB - A methodological framework is presented for the graph theoretical interpretation of NMR data of protein interactions. The proposed analysis generalizes the idea of network representations of protein structures by expanding it to protein interactions. This approach is based on regularization of residue-resolved NMR relaxation times and chemical shift data and subsequent construction of an adjacency matrix that represents the underlying protein interaction as a graph or network. The network nodes represent protein residues. Two nodes are connected if two residues are functionally correlated during the protein interaction event. The analysis of the resulting network enables the quantification of the importance of each amino acid of a protein for its interactions. Furthermore, the determination of the pattern of correlations between residues yields insights into the functional architecture of an interaction. This is of special interest for intrinsically disordered proteins, since the structural (three-dimensional) architecture of these proteins and their complexes is difficult to determine. The power of the proposed methodology is demonstrated at the example of the interaction between the intrinsically disordered protein osteopontin and its natural ligand heparin. PMID- 27272238 TI - Early prognostic factors at the time of diagnosis of bone metastasis in patients with bone metastases of differentiated thyroid carcinoma. AB - OBJECTIVE: Bone is the second most common site of distant metastases from differentiated thyroid cancer (DTC). Patients with bone metastases were associated with poor clinical outcomes; however, their clinical courses are heterogeneous. The aim of this study is to evaluate early prognostic factors of patients with bone metastases from DTC at the time of diagnosis of bone metastasis. METHODS: This retrospective study included 93 patients with bone metastases from DTC. We defined 'Pre-RAIT group' as patients whose bone metastases were detected before initial RAIT. The 'post-RAIT group' was defined as patients whose bone metastases were detected after initial RAIT or during the follow-up period. RESULTS: Median age was 55.4years, and 55 patients (59%) had papillary thyroid cancer. Patients in the pre-RAIT group (n=32) demonstrated significantly poorer overall survival (OS) (HR=1.86, P=0.04) than those in the post-RAIT group. There was no significant difference in the OS according to the initial RAI avidity among all patients (P=0.18). RAI-avid bone metastases had better OS only in the pre-RAIT group (HR=0.23, P=0.01) but not in the post-RAIT group. In the post-RAIT group, older age (>45years), elevated serum thyroglobulin (Tg) level (>250ng/mL), and the presence of skeletal-related events (SREs) were significantly associated with poor OS. RAI avidity was not a significant prognostic factor in the post-RAIT group (P=0.33). CONCLUSIONS: Patients whose bone metastases were diagnosed before initial RAIT demonstrate a poorer prognosis. RAI avidity is an early prognostic indicator in the pre-RAIT group. Old age, higher serum Tg levels, and SRE are associated with poor survival outcomes in the post-RAIT group. PMID- 27272237 TI - Treatment of diet-induced lipodystrophic C57BL/6J mice with long-acting PASylated leptin normalises insulin sensitivity and hepatic steatosis by promoting lipid utilisation. AB - AIMS/HYPOTHESIS: Recombinant leptin offers a viable treatment for lipodystrophy (LD) syndromes. However, due to its short plasma half-life, leptin replacement therapy requires at least daily subcutaneous (s.c.) injections. Here, we optimised this treatment strategy in LD mice by using a novel leptin version with extended plasma half-life using PASylation technology. METHODS: A long-acting leptin version was prepared by genetic fusion with a 600 residue polypeptide made of Pro, Ala and Ser (PASylation), which enlarges the hydrodynamic volume and, thus, retards renal filtration, allowing less frequent injection. LD was induced in C57BL/6J mice by feeding a diet supplemented with conjugated linoleic acid (CLA). Chronic and acute effects of leptin treatment were assessed by evaluating plasma insulin levels, insulin tolerance, histological liver sections, energy expenditure, energy intake and body composition. RESULTS: In a cohort of female mice, 4 nmol PAS-leptin (applied via four s.c. injections every 3 days) successfully alleviated the CLA-induced LD phenotype, which was characterised by hyperinsulinaemia, insulin intolerance and hepatosteatosis. The same injection regimen had no measurable effect when unmodified recombinant leptin was administered at an equivalent dose. In a cohort of LD males, a single s.c. injection of PAS-leptin did not affect energy expenditure but inhibited food intake and promoted a shift in fuel selection towards preferential fat oxidation, which mechanistically substantiates the metabolic improvements. CONCLUSIONS/INTERPRETATION: The excellent pharmacological properties render PASylated leptin an agent of choice for refining both animal studies and therapeutic strategies in the context of LD syndromes and beyond. PMID- 27272239 TI - Patient-specific Deformation Modelling via Elastography: Application to Image guided Prostate Interventions. AB - Image-guided prostate interventions often require the registration of preoperative magnetic resonance (MR) images to real-time transrectal ultrasound (TRUS) images to provide high-quality guidance. One of the main challenges for registering MR images to TRUS images is how to estimate the TRUS-probe-induced prostate deformation that occurs during TRUS imaging. The combined statistical and biomechanical modeling approach shows promise for the adequate estimation of prostate deformation. However, the right setting of the biomechanical parameters is very crucial for realistic deformation modeling. We propose a patient-specific deformation model equipped with personalized biomechanical parameters obtained from shear wave elastography to reliably predict the prostate deformation during image-guided interventions. Using data acquired from a prostate phantom and twelve patients with suspected prostate cancer, we compared the prostate deformation model with and without patient-specific biomechanical parameters in terms of deformation estimation accuracy. The results show that the patient specific deformation model possesses favorable model ability, and outperforms the model without patient-specific biomechanical parameters. The employment of the patient-specific biomechanical parameters obtained from elastography for deformation modeling shows promise for providing more precise deformation estimation in applications that use computer-assisted image-guided intervention systems. PMID- 27272240 TI - [Prevalence and Co-prevalence of Complex Regional Pain Syndrome (CRPS) and Carpal Tunnel Syndrome (CTS) in Hand Rehabilitation]. AB - BACKGROUND: In the current literature, there are reports of associations between complex regional pain syndromes (CRPS) and carpal tunnel syndromes (CTS). The aim of this study was to determine the prevalence of both disease patterns in hand rehabilitation patients and to investigate whether there is a correlation between CTS and CRPS. Furthermore, differences in the healing process of patients with and without additional CTS, and the effectiveness of the rehabilitative therapy for both diseases, were investigated. PATIENTS AND METHODS: The computerised medical records of 791 patients in the years 2009-2015 who had been in hand rehabilitation were retrospectively analysed. At the beginning and end of rehabilitation, measurements were made of pain by visual analogue scales (VAS, 0 10), grip strength and finger mobility (mean distance from finger pulp to palmar D2-D5). The clinical course was statistically analysed. CRPS diagnosis was confirmed clinically by a pain therapist, CTS diagnosis was confirmed by neurological and neurophysiological examination. Surgical therapy was performed despite CRPS diagnosis. RESULTS: The prevalence of CRPS was 161/1000 and of CTS 62/1000; the co-prevalence of the 2 diagnoses was 24/1000 (p<0.0001). In the CRPS group, after a mean of 8 (1-21) weeks of rehabilitative therapy, mean pain was reduced from 5 (1-10) to 3 (0-9), grip strength improved from 10 (0-39)kg to 18.5 (2.5-45.5)kg and finger mobility increased from 2.9 (0-7.6)cm to 1.8 (0-7.8)cm. In the CRPS+CTS group, after a mean of 6.8 (3-23) weeks of rehabilitative therapy, mean pain was reduced from 5 (0-8) to 2.6 (0-5), grip strength improved from 9.7 (2.4-25.5)kg to 17.4 (0.9-47.4)kg and finger mobility increased from 2.7 (0-5.3)cm to 1.7 (0-5.3)cm. Improvement over the period of rehabilitation was significant in both groups, though the period of therapy was significantly shorter in the CRPS+CTS group. CONCLUSION: CRPS and CTS are often associated. Rehabilitative therapy was effective for CRPS- and CRPS+CTS patients. PMID- 27272241 TI - An Integrative Theoretical Framework for HPV Vaccine Promotion Among Male Sexual Minorities. AB - The objective of the current study was to quantify the behavioral intentions of young adult male sexual minorities (MSM) to initiate human papillomavirus (HPV) vaccination and test an integrative model of HPV vaccine decision making. Participants were 575 MSM who were residing in the United States and were between ages 18 and 26 years. Standard direct and indirect measures of attitudes, perceived norms, and perceived behavioral control were employed to explain variation in behavioral intention. Additional background factors-such as concealment of one's sexual identity, suspicion of health care provider competence in LGBT health issues, perceived threat, and information orientation were also included in the model. The final model fit the data well and identified a set of salient attitudinal and control beliefs as the strongest determinants of intention ( R2 = .38). Perceived threat and information orientation were positively correlated with HPV-related beliefs. Perceived threat was higher among men infected with HIV and lower among men in monogamous relationships. Self efficacy, as an indirect measure of perceived behavioral control, was inversely related to the general tendency to conceal aspects of one's sexual orientation and a suspicion of health care providers. Bisexual identified men were more likely to conceal their sexual orientation and be more suspicious of health care providers. In this study, a number of modifiable determinants of HPV vaccine intentions-both psychosocial and environmental-were identified and have implications for targeted and tailored behavioral interventions to promote HPV vaccination among MSM. PMID- 27272244 TI - Scrutinizing Nonthermal Processes. PMID- 27272243 TI - 25th Anniversary of the TCM Hospital Bad Kotzting - Happy Birthday to You! PMID- 27272242 TI - Adding biotic complexity alters the metabolic benefits of mutualism. AB - Mutualism is ubiquitous in nature and plays an integral role in most communities. To predict the eco-evolutionary dynamics of mutualism it is critical to extend classic pair-wise analysis to include additional species. We investigated the effect of adding a third species to a pair-wise mutualism in a spatially structured environment. We tested the hypotheses that selection for costly excretions in a focal population (i) decreases when an exploiter is added (ii) increases when a third mutualist is added relative to the pair-wise scenario. We assayed the selection acting on Salmonella enterica when it exchanges methionine for carbon in an obligate mutualism with an auxotrophic Escherichia coli. A third bacterium, Methylobacterium extorquens, was then added and acted either as an exploiter of the carbon or third obligate mutualist depending on the nitrogen source. In the tripartite mutualism M. extorquens provided nitrogen to the other species. Contrary to our expectations, adding an exploiter increased selection for methionine excretion in S. enterica. Conversely, selection for cooperation was lower in the tripartite mutualism relative to the pair-wise system. Genome scale metabolic models helped identify the mechanisms underlying these changes in selection. Our results highlight the utility of connecting metabolic mechanisms and eco-evolutionary dynamics. PMID- 27272246 TI - Microwave Pasteurization of Cooked Pasta: Effect of Process Parameters on Texture and Quality for Heat-and-Eat and Ready-to-Eat Meals. AB - Pasta presents a challenge to microwave processing due to its unique cooking requirements. The objective of this study was to determine the effects of microwave processing on pasta physicochemical and mechanical properties. Fettuccine pasta was parboiled for selected times, then pasteurized using a Microwave Assisted Pasteurization System and stored under refrigeration for 1 wk. Samples were analyzed using microscopy, mechanical testing, and chemical analyses after storage. While no significant differences were observed for free amylose among fresh samples, samples parboiled for <=6 min had significantly higher free amylose, suggesting reduced starch retrogradation. Increased heat treatment increased degree of protein polymerization, observed in microstructures as increased gluten strand thickness and network density. Firmness and extensibility increased with increased parboil time; however, extension data indicated an overall weakening of microwave-treated pasta regardless of total cooking time. Overall, microwave pasteurization was shown to be a viable cooking method for pasta. PMID- 27272247 TI - Phytic Acid: From Antinutritional to Multiple Protection Factor of Organic Systems. AB - Several studies have shown the benefits of natural antioxidants on health and food preservation. Phytic acid (IP6) is a natural antioxidant that is found mainly in cereals and vegetables and, for a long period of time, was considered an antinutritional factor. However, in vitro and in vivo studies have demonstrated its beneficial effects in the prevention and treatment of several pathological conditions and cancer. Despite the numerous benefits of IP6, the signs and intracellular interactions mediated by this antioxidant remain poorly understood. This review describes the main chemical and biological aspects of IP6, as well as its actions in the prevention and treatment of various diseases. PMID- 27272248 TI - Temporal Check-All-That-Apply Characterization of Syrah Wine. AB - Temporal Check-All-That-Apply (TCATA) is a new dynamic sensory method for which analysis techniques are still being developed and optimized. In this study, TCATA methodology was applied for the evaluation of wine finish by trained panelists (n = 13) on Syrah wines with different ethanol concentrations (10.5% v/v and 15.5% v/v). Raw data were time standardized to create a percentage of finish duration, subsequently segmented into thirds (beginning, middle, and end) to capture panel perception. Results indicated the finish of the high ethanol treatments lasted longer (approximately 12 s longer) than the low ethanol treatment (P <= 0.05). Within each finish segment, Cochran's Q was conducted on each attribute and differences were detected amongst treatments (P <= 0.05). Pairwise tests showed the high ethanol treatments were more described by astringency, heat/ethanol burn, bitterness, dark fruit, and spices, whereas the low ethanol treatment was more characterized by sourness, red fruit, and green flavors (P <= 0.05). This study demonstrated techniques for dealing with the data generated by TCATA. Furthermore, this study further characterized the influence of ethanol on wine finish, and by extension wine quality, with implications to winemakers responsible for wine processing decisions involving alcohol management. PMID- 27272249 TI - Nonclassical MHC Ib-restricted CD8+ T Cells Recognize Mycobacterium tuberculosis Derived Protein Antigens and Contribute to Protection Against Infection. AB - MHC Ib-restricted CD8+ T cells have been implicated in host defense against Mycobacterium tuberculosis (Mtb) infection. However, the relative contribution of various MHC Ib-restricted T cell populations to anti-mycobacterial immunity remains elusive. In this study, we used mice that lack MHC Ia (Kb-/-Db-/-), MHC Ia/H2-M3 (Kb-/-Db-/-M3-/-), or beta2m (beta2m-/-) to study the role of M3 restricted and other MHC Ib-restricted T cells in immunity against Mtb. Unlike their dominant role in Listeria infection, we found that M3-restricted CD8+ T cells only represented a small proportion of the CD8+ T cells responding to Mtb infection. Non-M3, MHC Ib-restricted CD8+ T cells expanded preferentially in the lungs of Mtb-infected Kb-/-Db-/-M3-/- mice, exhibited polyfunctional capacities and conferred protection against Mtb. These MHC Ib-restricted CD8+ T cells recognized several Mtb-derived protein antigens at a higher frequency than MHC Ia restricted CD8+ T cells. The presentation of Mtb antigens to MHC Ib-restricted CD8+ T cells was mostly beta2m-dependent but TAP-independent. Interestingly, a large proportion of Mtb-specific MHC Ib-restricted CD8+ T cells in Kb-/-Db-/-M3-/ mice were Qa-2-restricted while no considerable numbers of MR1 or CD1-restricted Mtb-specific CD8+ T cells were detected. Our findings indicate that nonclassical CD8+ T cells other than the known M3, CD1, and MR1-restricted CD8+ T cells contribute to host immune responses against Mtb infection. Targeting these MHC Ib restricted CD8+ T cells would facilitate the design of better Mtb vaccines with broader coverage across MHC haplotypes due to the limited polymorphism of MHC class Ib molecules. PMID- 27272250 TI - Buffalo (Bubalus bubali) Late Embryo and Foetus Development: A Morphological Analysis. AB - Many researches describe the embryonic developmental features in domestic animals; however, in farm animals, they are scarce. Most farm animal studies are related to assisted reproduction and embryos transfer techniques. But, morphological features and size measure to estimate the age gestation are rarely reported in literature. Thus, in this study, we described the developmental changes in the bubaline (Bubalus bubali) concepts from 21 to 60 days of gestation. Our results revealed that buffalo embryos similar morphological characteristics similar to other mammalian species. Also, similarities between bovine and bubaline persist; except on foetal stages when buffalos have a faster development than bovine. Therefore, buffalo's gestation period exhibits some varieties and accurate embryo age is more difficult. Yet, when we use a combination of the crown-rump, macroscopic analysis and alizarin red, it is possible to describe better the whole embryogenesis stages of the buffalo and which can contribute for future reproduction researches and applications in veterinary practice. PMID- 27272251 TI - X-ray computed tomography datasets for forensic analysis of vertebrate fossils. AB - We describe X-ray computed tomography (CT) datasets from three specimens recovered from Early Cretaceous lakebeds of China that illustrate the forensic interpretation of CT imagery for paleontology. Fossil vertebrates from thinly bedded sediments often shatter upon discovery and are commonly repaired as amalgamated mosaics grouted to a solid backing slab of rock or plaster. Such methods are prone to inadvertent error and willful forgery, and once required potentially destructive methods to identify mistakes in reconstruction. CT is an efficient, nondestructive alternative that can disclose many clues about how a specimen was handled and repaired. These annotated datasets illustrate the power of CT in documenting specimen integrity and are intended as a reference in applying CT more broadly to evaluating the authenticity of comparable fossils. PMID- 27272252 TI - 13th International Symposium on Urolithiasis. PMID- 27272253 TI - Evaluation of HUGE equation (hematocrit, urea, gender) performance for screening chronic kidney disease in clinically stable cirrhotic patients. PMID- 27272254 TI - Impact of renal involvement on survival in ANCA-associated vasculitis. AB - BACKGROUND: Renal involvement is a serious complication of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We describe the pattern of renal involvement and its correlation with outcomes. PATIENTS AND METHODS: Medical records of 92 patients seen in rheumatology clinic and diagnosed as AAV between January 2007 and June 2014 were analysed. Patients were classified as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA) and undifferentiated AAV. Overall and renal outcomes were analysed. Patients were classified as advanced renal failure (creatinine >5.7 mg/dl or requiring dialysis), deranged RFT not qualifying the above parameters, and normal renal function. RESULTS: Sixty-seven (72.8 %) patients had GPA, 14 (15.2 %) had MPA, 8 (8.7 %) had EGPA, and 3 (3.3 %) had undifferentiated AAV. Renal involvement was seen in 51 (55.4 %) patients (46.3 % of GPA patients, 78.6 % of MPA, 37.5 % of EGPA and 33.3 % of unclassifiable AAV patients). Renal involvement was more common in males (p = 0.008). Patients with renal involvement had higher mean BVAS scores as compared to patients without renal involvement (p < 0.01). Thirteen patients (25.5 %) presented with advanced renal failure (creatinine >5.7 mg/dl or requiring dialysis), 21 (41.2 %) had deranged renal functions but did not require dialysis, and the rest had proteinuria and active sediments with normal serum creatinine. Twenty-four patients (47.1 %) had good renal outcome with normal creatinine, 12 (23.5 %) had persistent renal insufficiency, 12 (23.5 %) died, and one (2 %) remained dialysis dependent. Mean survival and mortality did not differ in patients with and without renal involvement (p = 0.454, p = 0.388). CONCLUSIONS: Renal involvement was more common in males. BVAS was higher in patients with renal involvement. The mean survival and mortality were similar in patients with or without renal involvement. PMID- 27272255 TI - Association between PAI-1 4G/5G polymorphism and diabetic nephropathy: a meta analysis in the Chinese population. AB - BACKGROUNDS AND AIMS: Although a number of studies have been conducted on the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and diabetic nephropathy (DN) in Chinese population, this association remains elusive and controversial. To further assess the effects of PAI-1 4G/5G polymorphism on the risk of DN, a meta-analysis was performed in the Chinese population. METHODS: Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through November, 2015. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: This meta-analysis identified nine studies, including 777 DN cases, 413 healthy controls, and 523 DM controls. In the total analyses, a significantly elevated risk of DN was associated with variants of PAI-1 4G/5G when compared with the healthy group (4G vs. 5G, OR 2.46, 95 % CI 1.45-4.16; 4G/4G vs. 5G/5G, OR 4.32, 95 % CI 1.79-10.39; 4G/4G vs. 4G/5G +5G/5G, OR 2.96, 95 % CI 1.59-5.53; 4G/4G +4G/5G vs. 5G/5G, OR 2.78, 95 % CI 1.34 5.75) and DM group (4G vs. 5G, OR 1.93, 95 % CI 1.28-2.92; 4G/4G vs. 5G/5G, OR 2.99, 95 % CI 1.44-6.21; 4G/4G vs. 4G/5G +5G/5G, OR 2.84, 95 % CI 1.77-4.54). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China. CONCLUSIONS: This meta-analysis showed that the PAI-1 4G/4G variant, 4G allele might be risk alleles for DN susceptibility in the Chinese population, and further studies in other ethic groups are required for definite conclusions. PMID- 27272257 TI - Effects of different levels of sanguinarine on antioxidant indices, immunological responses, ileal microbial counts and jejunal morphology of laying hens fed diets with different levels of crude protein. AB - This study was carried out to assess the effects of different levels of sanguinarine on antioxidant indices, immunological responses, serum biochemical parameters, ileal microbial counts and jejunal morphology of laying hens fed on diets with different levels of crude protein (CP). A total of 180 laying hens were subjected into nine dietary treatments with four cages of five birds each. Experimental treatments consisted of three levels of CP (85.0, 92.5 and 100% of Hy-Line W36 manual recommendation) and three levels of sanguinarine (0.00, 3.75 and 7.50 mg/kg) as a 3 * 3 factorial arrangement of laying hens which fed during a 70-day feeding trial. The in vitro study showed that sanguinarine exhibited sevenfold and threefold decreased antioxidant activities to inhibit 2-2-diphenyl 1-picric hydrazyl free radical as well as ferric ion reducing rather than butylated hydroxyl toluene. Although using the decremental levels of CP caused the increase in heterophil-to-lymphocyte ratio (p < 0.01), dietary administration of sanguinarine could suppress the serum cholesterol and malondialdehyde concentrations as well as heterophil-to-lymphocyte ratio (p < 0.05). Additionally, decreasing CP content resulted in the decreased percentage of albumin (p < 0.05); however, it had no negative effects on humoral immunity. Nonetheless, feeding of at least 3.75 mg/kg sanguinarine led to the remarkable increases in serum gamma globulin concentration (p < 0.01) and secondary (p < 0.05) antibody titres against sheep red blood cells. Moreover, a decline in dietary CP content led to higher villi height and crypt depth (p < 0.05; p < 0.001) and consequently decreased villi height-to-crypt depth ratio (p < 0.001) than the optimum level (100% CP). In spite of the effects of sanguinarine on the suppression of Escherichia coli and Salmonella counts (p < 0.05), it markedly enhanced villi height-to-crypt depth ratio as well as lamina propria lymphatic follicles extent, simultaneously (p < 0.001). Therefore, in spite of the detrimental effects of feeding low-CP diets on lymphocytes and serum albumin percentages, and villi height-to-crypt depth ratio, the administration of incremental levels of sanguinarine could improve cellular and humoral immunity, decrease ileal microbial counts and in turn improve the intestinal health indices in laying hens. PMID- 27272256 TI - Clinicopathological characteristics of non-diabetic renal disease in patients with type 2 diabetes mellitus in a northeastern Chinese medical center: a retrospective analysis of 273 cases. AB - OBJECTIVE: To investigate the clinical and histopathological features of non diabetic renal disease (NDRD) superimposed on diabetic nephropathy (DN) in northeastern Chinese patients with type 2 diabetes mellitus (T2D), and compare the changes with those of pure DN and isolated NDRD. METHODS: Single-center retrospective analysis based on medical records of 273 patients (172 men, mean age: 51.1 +/- 12.4 years) with T2D who underwent renal biopsy between February 2000 and October 2015. All patients were diagnosed as cases of pure DN, isolated NDRD or NDRD superimposed on DN. RESULTS: Out of the 273 T2D patients, 68 (24.9 %) had DN, 175 (64.1 %) had NDRD, and 30 (11.0 %) had NDRD superimposed on DN. Idiopathic membranous nephropathy (IMN, 29.7 %) was the most common NDRD followed by IgA nephropathy (IgAN, 22.9 %), and hypertensive renal arteriolar sclerosis was the most common lesion in patients diagnosed as NDRD superimposed on DN. Patients with NDRD had a shorter duration of diabetes and lower frequencies of diabetic retinopathy (DR, 6.9 %) and renal failure (28.0 %), which is consistent with higher estimated glomerular filtration rates (eGFR) and lower systolic blood pressure (SBP). No significant between-group differences were observed with respect to proteinuria and hematuria. CONCLUSION: Renal biopsy is strongly recommended for T2D patients to distinguish DN, NDRD and NDRD superimposed on DN, especially in patients with no signs of DR. This approach may help in early diagnosis and treatment of NDRD and improve renal outcomes in northeastern Chinese T2D patients. PMID- 27272258 TI - Introduction of d-Glutamate at a Critical Residue of Abeta42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity. AB - The amyloid beta peptide 42 (Abeta42) is an aggregation-prone peptide that plays a pivotal role in Alzheimer's disease. We report that a subtle perturbation to the peptide through a single chirality change at glutamate 22 leads to a pronounced delay in the beta-sheet adoption of the peptide. This was accompanied by an attenuated propensity of the peptide to form fibrils, which was correlated with changes at the level of the fibrillary architecture. Strikingly, the incorporation of d-glutamate was found to stabilize a soluble, ordered macromolecular assembly with enhanced cytotoxicity to PC12 cells, highlighting the importance of advanced prefibrillary Abeta aggregates in neurotoxicity. PMID- 27272259 TI - Phase separation and mechanical properties of an elastomeric biomaterial from spider wrapping silk and elastin block copolymers. AB - Elastin and silk spidroins are fibrous, structural proteins with elastomeric properties of extension and recoil. While elastin is highly extensible and has excellent recovery of elastic energy, silks are particularly strong and tough. This study describes the biophysical characterization of recombinant polypeptides designed by combining spider wrapping silk and elastin-like sequences as a strategy to rationally increase the strength of elastin-based materials while maintaining extensibility. We demonstrate a thermo-responsive phase separation and spontaneous colloid-like droplet formation from silk-elastin block copolymers, and from a 34 residue disordered region of Argiope trifasciata wrapping silk alone, and measure a comprehensive suite of tensile mechanical properties from cross-linked materials. Silk-elastin materials exhibited significantly increased strength, toughness, and stiffness compared to an elastin only material, while retaining high failure strains and low energy loss upon recoil. These data demonstrate the mechanical tunability of protein polymer biomaterials through modular, chimeric recombination, and provide structural insights into mechanical design. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 693-703, 2016. PMID- 27272267 TI - Case Series With Histopathologic and Radiographic Analyses Following Failure of Fresh Osteochondral Allografts of the Talus. AB - BACKGROUND: Fresh osteochondral allografting of the talus is one treatment option for large chondral defects. Following positive early term results, failure rates of up to 35% have been reported. A retrieval study was performed to characterize failed talar allografts. METHODS: Failed fresh osteochondral allografts of the talus were retrieved on revision. Cases of deep infection were excluded. After tissue fixation, samples were decalcified, embedded, and stained with Safranin O/Fast Green, osteocalcin, tumor necrosis factor alpha (TNF-alpha), CD4, CD8, and CD68. Slides were graded according to the modified Mankin scoring system or severity scale. Medical record review was performed. RESULTS: Eight allografts (7 patients) were retrieved from patients, following an average term of implantation of 31 months (range, 12-58). There were 3 types of allografts in this series (hemidome, n=5; segmental, n=2; bipolar, n=1). Reasons for transplantation were post-traumatic arthritis or osteonecrosis; reasons for revision were graft failure/collapse, nonunion, progressive arthritis, and/or pain. Prior to revision, all grafts exhibited collapse and subchondral lucencies. At the graft host interface, Safranin-O staining demonstrated substantial loss of sulfated glycosaminoglycans, Osteocalcin immunostaning was nearly absent, CD68 (indicating osteoclast activity) was predominantly exhibited, and CD4+ helper T cells as well as CD8+ cytotoxic T cells and NK cells-cell types commonly implicated in allogeneic organ transplant rejection-were found in high concentrations. TNF alpha was present throughout the graft. CONCLUSION: A histopathologic analysis of 8 retrieved, failed talar allografts was performed. Graft failure appeared to be primarily biologic, with an extensive loss of viable cartilaginous and osseous tissue at the graft-host interface. This study provides the first evidence of a potential CD4+ and CD8+ lymphocyte-mediated failure mechanism in fresh osteochondral allografts that were revised following collapse. LEVEL OF EVIDENCE: Level IV, case series. PMID- 27272268 TI - Optimising Breast Conservation Treatment for Multifocal and Multicentric Breast Cancer: A Worthwhile Endeavour?: Reply. PMID- 27272266 TI - Pharmacokinetics and Dosing of Ceftobiprole Medocaril for the Treatment of Hospital- and Community-Acquired Pneumonia in Different Patient Populations. AB - Hospital-acquired pneumonia (HAP) and community-acquired pneumonia (CAP) are among the most common infections treated in the hospital setting, and together they place a significant burden on healthcare systems. Successful management of HAP and CAP depends on rapid initiation of empirical antibiotic therapy with broad-spectrum antibiotics. Ceftobiprole is a new-generation, broad-spectrum cephalosporin antibiotic for the treatment of HAP (excluding ventilator associated pneumonia) and CAP. It displays potent in vitro activity against a broad range of pathogens important in pneumonia. This review summarizes the pharmacokinetic profile of ceftobiprole, and considers the pharmacokinetic parameters and pharmacodynamics underlying the choice of dosing regimen. Ceftobiprole shows linear pharmacokinetics after single and multiple doses and is eliminated predominantly through the kidneys. Ceftobiprole is administered as a 500 mg intravenous infusion over 2 h every 8 h, and steady-state concentrations are reached on the first day of dosing. Dose adjustment is recommended for patients with moderate or severe renal impairment and for those with end-stage renal disease. Extending the infusion time of ceftobiprole to 4 h is recommended to optimize drug exposure in critically ill patients with augmented renal clearance. However, there is no need for dose adjustments based on age, sex or ethnicity, or for patients with severe obesity. Population pharmacokinetic modelling and Monte Carlo simulations were used to determine the optimal dosing regimen for ceftobiprole in special patient populations, including paediatric patients. Future studies of ceftobiprole in patients with HAP and CAP would be of interest. PMID- 27272269 TI - Should Gastric Decompression be a Routine Procedure in Patients Who Undergo Pylorus-Preserving Pancreatoduodenectomy? AB - BACKGROUND: Nasogastric tube placement after abdominal surgery has been a standard procedure for many decades. In pancreatoduodenectomy, delayed gastric emptying (DGE) is still a leading postoperative complication, often resulting in patient anxiety or depression and prolonged hospital stays. Such complications have led many surgeons to prefer postoperative nasogastric decompression because of the greater risk of DGE. Therefore, the goal of this study was to evaluate the DGE and perioperative outcomes after pylorus-preserving pancreatoduodenectomy (PPPD) with or without routine gastrostomy. METHODS: From May 2009 to December 2014, 228 patients underwent PPPD at the Department of Surgery, Gangnam Severance Hospital, Yonsei University. The first cohort of 116 patients underwent surgery before June 2012 and uniformly underwent gastric decompression as a part of postoperative management. The second cohort of 112 patients underwent operation after July 2012, and gastric decompression was selectively used to facilitate exposure during operation and was removed in the operating room at the end of surgery. We evaluated DGE incidence, time to dietary tolerance, length of hospital stay, and postoperative gastric tube reinsertion rates. RESULTS: Gastric re-decompression was necessary in 38 patients (16.7 %), and there was a significant difference between the two groups (p = 0.006). Eleven (9.8 %) patients in the no-tube gastrostomy group required nasogastric tube reinsertion, and 27 (23.3 %) in the routine gastrostomy group required that the gastrostomy tube be re-drainage. There were no statistically significant differences in the frequency or severity of complications such as delayed gastric emptying or pancreatic leakage. CONCLUSIONS: Our study demonstrates that routine postoperative gastric decompression can be safely avoided in patients who undergo PPPD. PMID- 27272272 TI - Autonomic Nervous System and the Liver. AB - The liver is innervated by both the sympathetic and the parasympathetic nerve systems. These nerves are derived from the splanchnic and vagal nerves that surround the portal vein, hepatic artery, and bile duct. The afferent fiber delivers information regarding osmolality, glucose level, and lipid level in the portal vein to the central nervous system (CNS). In contrast, the efferent fiber is crucial in the regulation of metabolism, blood flow, and bile secretion. Furthermore, liver innervation has been associated with hepatic fibrosis, regeneration, and circadian rhythm. Knowledge of these mechanisms can be applied for potential liver disease treatment. PMID- 27272271 TI - Risk Evaluation of Postoperative Delirium Using Comprehensive Geriatric Assessment in Elderly Patients with Esophageal Cancer. AB - BACKGROUND: The number of geriatric patients with esophageal cancer is increasing in step with the aging of the population. Geriatric patients have a higher risk of postoperative complications, including delirium that can cause a fall or impact survival. Therefore, it is very important that we evaluate risks of postoperative complications before surgery. The aim of this study was to predict postoperative delirium in elderly patients. METHODS: We retrospectively reviewed the medical records of 91 patients aged 75 years and over who underwent esophagectomy between January 2006 and December 2014. We investigated the association between postoperative delirium and clinicopathological factors, including comprehensive geriatric assessment (CGA). RESULTS: Postoperative delirium developed in 24 (26 %) patients. Postoperative delirium was significantly associated with low mini-mental state examination (MMSE) and high Geriatric Depression Scale 15 (GDS15), which are components of CGA, and psychiatric disorder (P < 0.0001, P = 0.002, and P = 0.017, respectively). With multiple logistic regression analysis, MMSE (odds ratio [OR], 1.4; 95 % confidence interval [CI], 1.2-1.6; P < 0.0001] and GDS15 (OR, 1.3; 95 % CI, 1.1 1.6; P = 0.004) were independently associated with postoperative delirium. CONCLUSIONS: Preoperative CGA, especially MMSE and GDS15, was useful for predicting postoperative delirium in elderly patients undergoing esophagectomy for esophageal cancer. Intervention by a multidisciplinary team using CGA might help prevent postoperative delirium. PMID- 27272270 TI - Central Hepatectomy versus Extended Hepatectomy for Malignant Tumors: A Propensity Score Analysis of Postoperative Complications. AB - BACKGROUND: The specific definition of central hepatectomy (CH) (i.e., resection of segments 4-5-8 +/- 1) is not uniformly used, resulting in conflicting comparisons with the more commonly performed extended hepatectomy (EH). The study aimed to compare, using propensity score matching (PSM) analysis, the incidence of postoperative complications between CH and EH for centrally located liver tumors (CLLT). METHODS: All consecutive CH and EH procedures for CLLT performed from 1980 to 2011 were retrospectively reviewed. Independent predictors of postoperative complications were identified. CH was compared to EH after PSM. RESULTS: The study population consisted of 373 patients, 44 (11.8 %) of whom underwent CH and 329 (88.2 %) of whom underwent EH. Before PSM, the overall 90 day mortality was 7.2 % (27 patients) without a group difference (2 (4.5 %) for CH vs. 25 (7.6 %) for EH, p = 0.756). The CH and EH groups had similar postoperative morbidity rates (43.2 vs. 55.3 %; p = 0.108). Blood transfusion was the only independent predictor of postoperative complications (Hazard Ratio: 1.73; 95 % confidence interval: 1.11-2.68; p = 0.014). After PSM, 43 CH patients were matched with 43 EH patients. No group difference was observed for the postoperative mortality, morbidity, or duration of hospital stay. A higher number of EH patients (30.2 vs. 9.3 %, p = 0.028) presented with more than one postoperative complication. CONCLUSIONS: CH and EH yield similar mortality and morbidity. For CLLT, CH may be an attractive procedure with the advantage of sparing the liver parenchyma compared with EH. PMID- 27272273 TI - Control of an Outbreak of Middle East Respiratory Syndrome in a Tertiary Hospital in Korea. AB - BACKGROUND: In 2015, a large outbreak of Middle East respiratory syndrome (MERS) occurred in the Republic of Korea. Half of the cases were associated with a tertiary care university hospital. OBJECTIVE: To document the outbreak and successful control measures. DESIGN: Descriptive study. SETTING: A 1950-bed tertiary care university hospital. PATIENTS: 92 patients with laboratory confirmed MERS and 9793 exposed persons. MEASUREMENTS: Description of the outbreak, including a timeline, and evaluation of the effectiveness of the control measures. RESULTS: During the outbreak, 92 laboratory-confirmed MERS cases were associated with a large tertiary care hospital, 82 of which originated from unprotected exposure to 1 secondary patient. Contact tracing and monitoring exposed patients and assigned health care workers were at the core of the control measures in the outbreak. Nontargeted screening measures, including body temperature screening among employees and visitors at hospital gates, monitoring patients for MERS-related symptoms, chest radiographic screening, and employee symptom monitoring, did not detect additional patients with MERS without existing transmission links. All in-hospital transmissions originated from 3 patients with MERS who also had pneumonia and productive cough. LIMITATIONS: This was a retrospective single-center study. Statistical analysis could not be done. Because this MERS outbreak originated from a superspreader, effective control measures could differ in endemic areas or in other settings. CONCLUSION: Control strategies for MERS outbreaks should focus on tracing contacts of persons with epidemiologic links. Adjusting levels of quarantine and personal protective equipment according to the assumed infectivity of each patient with MERS may be appropriate. PRIMARY FUNDING SOURCE: Samsung Biomedical Research Institute. PMID- 27272274 TI - Sucrose Sensitivity of Honey Bees Is Differently Affected by Dietary Protein and a Neonicotinoid Pesticide. AB - Over a decade, declines in honey bee colonies have raised worldwide concerns. Several potentially contributing factors have been investigated, e.g. parasites, diseases, and pesticides. Neonicotinoid pesticides have received much attention due to their intensive use in crop protection, and their adverse effects on many levels of honey bee physiology led the European Union to ban these compounds. Due to their neuronal target, a receptor expressed throughout the insect nervous system, studies have focused mainly on neuroscience and behaviour. Through the Geometric Framework of nutrition, we investigated effects of the neonicotinoid thiamethoxam on survival, food consumption and sucrose sensitivity of honey bees (Apis mellifera). Thiamethoxam did not affect protein and carbohydrate intake, but decreased responses to high concentrations of sucrose. Interestingly, when bees ate fixed unbalanced diets, dietary protein facilitated better sucrose detection. Both thiamethoxam and dietary protein influenced survival. These findings suggest that, in the presence of a pesticide and unbalanced food, honey bee health may be severely challenged. Consequences for foraging efficiency and colony activity, cornerstones of honey bee health, are also discussed. PMID- 27272275 TI - Does type 2 diabetes mellitus promote intervertebral disc degeneration? AB - PURPOSE: LDD is an important cause of low back pain. Many people believe there is an adverse influence of type 2 diabetes (T2D) on lumbar intervertebral disc degeneration (LDD). We examined a population sample for epidemiological evidence of association. METHODS: Twin volunteers from the TwinsUK cohort having spine magnetic resonance (MR) scans coded for LDD and information about T2D were investigated in two ways. First, as a population sample and second as a cotwin case control study in twin pairs discordant for T2D. Other risk factors for LDD considered were age, body-mass index (BMI), smoking, and alcohol. RESULTS: In 956 twin volunteers T2D had a prevalence of 6.6 %. LDD score was higher in T2D twins (14.9 vs 13.1 p = 0.04) but was not an independent risk factor if the influence of age and BMI were included in the model. Discordant twin analysis (n = 33 pairs) showed no significant difference in LDD between twins having T2D and their unaffected cotwins. CONCLUSIONS: Twins having T2D did manifest higher LDD scores but the effect was abrogated once BMI was included in multivariable analysis, showing it is not an independent risk factor for LDD. The population study had 80 % power at 0.1 significance level to detect a difference of 1.8 in LDD score (range of 0-60), so if there is an effect of T2D on LDD, it is likely to be small. PMID- 27272276 TI - Dynamic global sagittal alignment evaluated by three-dimensional gait analysis in patients with degenerative lumbar kyphoscoliosis. AB - PURPOSE: Sagittal vertical axis (SVA) is the most commonly used parameter for evaluating global sagittal alignment (GSA) in a static condition. However, its dynamic statuses remain unclear. The aim of this study was to evaluate dynamic GSA of degenerative lumbar kyphoscoliosis (DLKS) using three-dimensional motion analysis system (3D-MAS). METHODS: Twenty-six patients with DLKS underwent gait analysis using 3D-MAS. Static (S-) and dynamic (D-) trunk angle (TA) (the angle between the vertical axis and the line connecting C7 and S1 spinous processes) and S-sagittal trunk shift (STS) and D-STS (the distance between the two vertical lines running through C7 and S1 spinous process) were recorded during treadmill walking. Pelvic angle (PA) (the angle between the horizontal axis and the line connecting the posterior and anterior superior iliac spine) were also recorded. S PA and D-PA represent retroversion or anteversion of the pelvis, which can be substituted for pelvic tilt. As to dynamic parameters, those at the initial five steps (Di) and the final five steps (Df) of treadmill walking were also recorded. RESULTS: The median S-TA, S-STS, and S-PA were 16.0 degrees , 11.9 cm, and -5.5 degrees (retroversion). The median D parameters were Di-TA/Df-TA 21.8 degrees /26.9 degrees ; Di-STS/Df-STS 14.1/21.1 cm; and Di-PA/Df-PA 15.7 degrees /22.8 degrees (anteversion). All D parameters were significantly greater than S parameters (P < 0.01) and all Df parameters were also significantly worse than Di parameters (P < 0.001). Thus, compensated GSA by pelvic retroversion in static condition was lost due to anteversion change of the pelvis immediately after start of walking and worsened over time. CONCLUSION: Dynamic GSA assessment using 3D-MAS can avoid underestimation of GSA loss that is detected by static standing full-length radiography. PMID- 27272278 TI - Improved photocatalytic hydrogen evolution driven by chloro(terpyridine)platinum(ii) derivatives tethered to a single pendant viologen acceptor. AB - Three chloro(4'-(N-methylpyridinium)-2,2':6',2''-terpyridine)platinum(ii) (abbreviated as ) derivatives tethered to a single alkyl viologen unit (-(CH2)n CH2-N(+)C5H4-C5H4N(+)-CH3; abbreviated as -, where n = 1, 3, and 4), i.e., , have been synthesized and investigated in detail. It is shown that the turnover number (TON) for the photocatalytic H2 evolution from water in the presence of a sacrificial electron donor EDTA (ethylenediaminetetraacetic acid disodium salt) is dramatically improved by the attachment of a single alkyl unit (TON = 21.5 25.2, 12 h). Spectrophotometric studies reveal that the photoirradiation of in the presence of EDTA initially leads to the formation of a 1-electron-reduced species, and then to a 2-electron-reduced species, where reductive quenching of a photoexcited species is a major path to the reduced photoproduct in each step. Electrochemical studies show that two consecutive 1-electron reductions at the unit are nearly overlapped with the corresponding reductions at the unit. The 1 electron-reduced species can be thus expressed as either or , while the 2 electron-reduced one as . Moreover, the latter products behave as stacked species involving three types of pi-dimer sites, ()2, ()2, and ()(), and do not drive thermal H2 evolution according to the reaction: + 2H(+) -> + H2. The H2 evolution from water photocatalyzed by has been found to occur via formation of 3-electron reduced species; + EDTA + hnu -> (or ) + EDTA(ox), and (or ) + 2H(+) -> (or ) + H2. PMID- 27272277 TI - Validity and responsiveness of the French version of the Orebro Musculoskeletal Pain Screening Questionnaire in chronic low back pain. AB - PURPOSE: The assessment of a broad range of biopsychosocial aspects is important in the rehabilitation of patients with chronic low back pain (CLBP) for the prediction of outcome as well as for evaluation. The objective of this study was to test the responsiveness, construct validity and predictive value of the Orebro Musculoskeletal Pain Screening Questionnaire (OMPSQ) compared to other instruments widely used to assess biopsychosocial aspects in patients with CLBP. METHODS: 111 patients with CLBP admitted to an inpatient rehabilitation completed a set of questionnaires on biopsychosocial aspects at baseline and at discharge. Ninety-eight patients responded at three months for an assessment of the return to work status. Responsiveness of the OMPSQ, the ability to detect change in the construct of interest, was investigated by a set of hypotheses on correlations with widely used questionnaires. We tested the hypothesis that the changes in the OMPSQ would vary along with the responses in the Patient's Global Impression of Change. Prediction of disability at discharge, work status at three months and time to return to work was evaluated with linear, logistic and cox regression models. RESULTS: The OMPSQ showed good predictive values for disability and return to work and construct validity of the instrument was corroborated. Seventy nine percent of our hypotheses for responsiveness could be confirmed, with the OMPSQ showing the second highest change during the rehabilitation. CONCLUSIONS: The OMPSQ can also be applied in patients with CLBP, but for the assessment of change in psychosocial variables one should add specific questionnaires. PMID- 27272279 TI - Pharmacokinetics of single dose radium-223 dichloride (BAY 88-8223) in Japanese patients with castration-resistant prostate cancer and bone metastases. AB - OBJECTIVE: This open-label, non-randomized, phase I study examined the pharmacokinetics (PK) and radiation dosimetry of a single dose of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastases. METHODS: Six male Japanese patients (mean age 72.5 years, range 65-79 years) with histologically or cytologically confirmed stage IV adenocarcinoma of the prostate were recruited. A single IV dose of radium-223 was delivered intravenously (IV) via slow bolus over a 2-5 min period: Cohort 1 received 50 kBq/kg and Cohort 2 received 100 kBq/kg. RESULTS: Following IV injection, radium 223 was rapidly eliminated from the blood in a multi-phasic manner. The fraction of the injected activity of radium-223 retained in the whole body 24 h following injection was 85 %. Biodistribution results showed initial bone uptake was 52 % (range 41-57 %). The maximum activity of radium-223 in the bone was observed within 2 h of dosing. Activity of radium-223 passed through the small intestine within 24 h. No activity was detected in other organs. The major radiation dose from radium-223 was found in osteogenic cells; calculated absorbed doses in osteogenic cells and in the red marrow were 0.76 Gy/MBq and 0.09 Gy/MBq, respectively. CONCLUSIONS: In Japanese patients with CRPC and bone metastases, radium-223 (IV) achieved maximum activity in the bone rapidly and passed through the intestine within 24 h, without signs of activity in other organs. The PK profile and absorbed radiation dose in organs and tissues in Japanese patients were similar to data from non-Japanese patients. Trial registration identification: NCT01565746. PMID- 27272282 TI - Forthcoming in Zoo Biology. PMID- 27272280 TI - Reply to the Letter to the Editor: Does Degenerative Lumbar Spine Disease Influence Femoroacetabular Flexion in Patients Undergoing Total Hip Arthroplasty? PMID- 27272283 TI - Instructions for Contributors. PMID- 27272285 TI - Addressing reimbursement disparities for direct-acting antiviral therapies for hepatitis C virus infection is essential to ensure access for all. PMID- 27272286 TI - [Rapid Report Hemophilia. Evidence in treatment of hemophilia from the IQWiG's perspective]. AB - : The German Institute for Quality and Efficiency in Health Care (IQWiG) conducted a rapid report to assess the therapy of hemophilia patients. Based on a systematic literature search the IQWiG identified 16 studies which show that there is now sufficient information regarding questions that previously lacked data. A benefit assessment of prophylactic and on-demand-treatment concerning different treatment outcomes shows the superiority of the prophylactic therapy regarding major bleedings for all age groups. For the group of youths and adults the analysis shows additional benefits concerning health status and pain within the preceding four weeks. The alignment of guidelines with the identified evidence shows minor correspondence between the guidelines' references and included studies. However, the guidelines' statements primarily correspond with the results of the conducted benefit assessment. CONCLUSION: The IQWiG's rapid report shows prophylactic therapy to be superior to on-demand therapy. These findings represent a clear indication for attending physicians and payers for prophylaxis in patients with severe hemophilia A. PMID- 27272287 TI - Clinical nurses' knowledge and practice of venous thromboembolism risk assessment and prevention in South Korea: a cross-sectional survey. AB - AIMS AND OBJECTIVES: To examine Korean registered nurses' level of perceived knowledge and practice of venous thromboembolism risk assessment as well as prevention, self-efficacy in venous thromboembolism care and actual knowledge of venous thromboembolism. BACKGROUND: For hospitalised patients, venous thromboembolism is a preventable clinical disorder. Caring for venous thromboembolism patients requires coordination across multiple providers and settings. Clinical nurses can play a major role in improving venous thromboembolism prevention care, assessing venous thromboembolism risks and providing appropriate prophylactic measures to those who are at risk for venous thromboembolism. DESIGN: A cross-sectional descriptive study. METHODS: Anonymous paper-based surveys were conducted for a convenience sample of registered nurses' (n = 452) from two university-affiliated hospitals in South Korea. RESULTS: The majority of participants indicated that their overall self-rated venous thromboembolism knowledge was 'fair', while only 2.4% rated it as 'very good' or 'excellent'. The overall mean score of the venous thromboembolism knowledge questions was 50.9 (+/-13.0) of a possible score of 100. The mean score of self efficacy in practising venous thromboembolism prevention/prophylaxis was 3.0 (based on a one to five Likert scale). The self-reported venous thromboembolism assessment performance on patients varied among clinical units. Only 9.3% of participants reported having received in-service venous thromboembolism education from their hospital. CONCLUSIONS: The findings showed that overall venous thromboembolism knowledge and self-efficacy in venous thromboembolism prevention practices of Korean registered nurses' were not highly rated. Korean nurses demonstrated a lack of knowledge about venous thromboembolism, particularly in the areas of venous thromboembolism prophylaxis measures and venous thromboembolism diagnosis methods. RELEVANCE TO CLINICAL PRACTICE: Focused education on venous thromboembolism prevention and risk assessment should be considered a component of continuing education for Korean nurses. PMID- 27272288 TI - BJOG Editor's Choice: Intimate partner violence destroys love like tears blur clear vision. PMID- 27272290 TI - Vasa praevia: more than 100 years in preventing unnecessary fetal deaths. PMID- 27272291 TI - RhD immune globulin: over 50 years of remarkable progress! PMID- 27272292 TI - The increased perinatal mortality rate over weekends is proof that we require a 7 day maternity service: FOR: No baby should die simply because they are born at a weekend. PMID- 27272293 TI - The increased perinatal mortality rate over weekends is proof that we require a 7 day maternity service: AGAINST: Shifting resources towards delivery units and away from antenatal care could increase perinatal mortality. PMID- 27272294 TI - Patients are entitled to choose their surgeon. PMID- 27272295 TI - Courage. PMID- 27272297 TI - Re: External validation of the Paediatric Risk of Malignancy Index. PMID- 27272298 TI - Re: Cost-effectiveness of cervical cancer screening: cytology versus human papillomavirus DNA testing. PMID- 27272299 TI - Authors' reply re: Cost-effectiveness of cervical cancer screening: cytology versus human papillomavirus DNA testing. PMID- 27272300 TI - Re: Caesarean section should be available on request. PMID- 27272301 TI - Authors' reply re: Caesarean section should be available on request. PMID- 27272302 TI - Re: Twelve-month outcomes following midurethral sling procedures for stress incontinence: impact of obesity. PMID- 27272303 TI - Re: Caesarean hysterectomy for placenta praevia/accreta using an approach via the pouch of Douglas. PMID- 27272304 TI - Authors' reply re: Twelve-month outcomes following midurethral sling procedures for stress incontinence: impact of obesity. PMID- 27272305 TI - Author's reply re: Caesarean hysterectomy for placenta praevia/accreta using an approach via the pouch of Douglas. PMID- 27272306 TI - A report from #BlueJC: Who develops abnormally invasive placenta during pregnancy? PMID- 27272308 TI - Rigorous intensity and phase-shift manipulation in optical frequency conversion. AB - A simple method is employed to investigate the nonlinear frequency conversion in optical superlattices (OSL) with pump depletion. Four rigorous phase-matching conditions for different purposes are obtained directly from the nonlinear coupled equations, and the resulting OSL domain structures are generally aperiodic rather than periodic. With this method, not only the intensity but also the phase-shift of the harmonic waves can be manipulated at will. The second harmonic generation of Gaussian beam is further investigated. This work may provide a guidance for the practical applications of designing nonlinear optical devices with high conversion efficiency. PMID- 27272307 TI - Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture. AB - Influenza A virus is a significant public health threat, but little is understood about the viral RNA structure and function. Current vaccines and therapeutic options to control influenza A virus infections are mostly protein-centric and of limited effectiveness. Here, we report using an ensemble defect approach to design mutations to misfold regions of conserved mRNA structures in influenza A virus segments 7 and 8. Influenza A mutant viruses inhibit pre-mRNA splicing and attenuate viral replication in cell culture, thus providing evidence for functions of the targeted regions. Targeting these influenza A viral RNA regions provides new possibilities for designing vaccines and therapeutics against this important human respiratory pathogen. The results also demonstrate that the ensemble defect approach is an efficient way to test for function of RNA sequences. PMID- 27272309 TI - Congenital cholesteatoma together with ossicular chain anomaly. AB - Cholesteatomas that occur under an intact tympanic membrane in the absence of prior surgical procedures or perforation are defined as congenital cholesteatomas. These entities are rarely seen, because they do not cause any major symptoms unless they touch the ossicular chain. Likewise, isolated congenital ossicular anomalies that occur independently of external ear anomalies and craniofacial dysplasia are also rarely seen. Here, we report a patient who presented with congenital cholesteatoma associated with anomalies of the ossicular chain and discuss its pathogenesis. PMID- 27272310 TI - Cellular metabolism of myeloid cells in sepsis. AB - In recent years, it has become appreciated that immune cells have different metabolic profiles depending on their activation status. During sepsis, circulating leukocytes go through a hyperinflammatory state, which can be accompanied or followed by defective antimicrobial defenses (also described as immune tolerance or paralysis). In this review, the modulation of different cellular metabolic pathways during sepsis in monocytes and macrophages will be discussed. Glycolysis is studied extensively in sepsis and is up-regulated in hyperinflammatory cells, whereas in immune tolerance, it is often down-regulated. Few data are available on other metabolic pathways in immune cells from patients with sepsis. The pentose phosphate pathway is up-regulated during acute hyperinflammatory responses, whereas fatty acid beta-oxidation is increased later during sepsis and is associated with an anti-inflammatory (M2) phenotype of macrophages. Within the amino acid metabolism we will discuss the most studied metabolites. Collectively, these data argue that exploration of the immunometabolic pathways in sepsis is an important area of research, and the targeting of metabolic pathways may represent a promising novel strategy as a therapy of sepsis. PMID- 27272311 TI - Multiple myeloma cells promote migration of bone marrow mesenchymal stem cells by altering their translation initiation. AB - The role of the bone marrow microenvironment in multiple myeloma pathogenesis and progression is well recognized. Indeed, we have shown that coculture of bone marrow mesenchymal stem cells from normal donors and multiple myeloma cells comodulated translation initiation. Here, we characterized the timeline of mesenchymal stem cells conditioning by multiple myeloma cells, the persistence of this effect, and the consequences on cell phenotype. Normal donor mesenchymal stem cells were cocultured with multiple myeloma cell lines (U266, ARP1) (multiple myeloma-conditioned mesenchymal stem cells) (1.5 h,12 h, 24 h, 48 h, and 3 d) and were assayed for translation initiation status (eukaryotic translation initiation factor 4E; eukaryotic translation initiation factor 4G; regulators: mechanistic target of rapamycin, MNK, 4EBP; targets: SMAD family 5, nuclear factor kappaB, cyclin D1, hypoxia inducible factor 1, c-Myc) (immunoblotting) and migration (scratch assay, inhibitors). Involvement of mitogen-activated protein kinases in mesenchymal stem cell conditioning and altered migration was also tested (immunoblotting, inhibitors). Multiple myeloma conditioned mesenchymal stem cells were recultured alone (1-7 d) and were assayed for translation initiation (immunoblotting). Quantitative polymerase chain reaction of extracted ribonucleic acid was tested for microRNAs levels. Mitogen activated protein kinases were activated within 1.5 h of coculture and were responsible for multiple myeloma-conditioned mesenchymal stem cell translation initiation status (an increase of >200%, P < 0.05) and elevated migration (16 h, an increase of >400%, P < 0.05). The bone marrow mesenchymal stem cells conditioned by multiple myeloma cells were reversible after only 1 d of multiple myeloma-conditioned mesenchymal stem cell culture alone. Decreased expression of microRNA-199b and microRNA-125a (an increase of <140%, P < 0.05) in multiple myeloma-conditioned mesenchymal stem cells supported elevated migration. The time and proximity-dependent conditioning of normal donor mesenchymal stem cells in our model points to a dynamic interaction between multiple myeloma cells and the bone marrow niche, which causes profound changes in the nonmalignant bone marrow constituents. Future studies are warranted to identify clinically relevant means of blocking this crosstalk and improving multiple myeloma therapy. PMID- 27272312 TI - Long-term follow-up of intravesical botulinum toxin-A injections in women with idiopathic overactive bladder symptoms. AB - INTRODUCTION: Intravesical botulinum toxin (BoNT-A) is a safe and effective treatment for overactive bladder syndrome. There are many reports on the clinical experience with BoNT-A, especially in patients with neurogenic detrusor overactivity. The US Food and Drug Administration has recently approved its use for idiopathic overactive bladder (iOAB). Various studies have reported positive results for iOAB in the short-term. Yet little is known about the results after repeated BoNT-A injections. In this study, we evaluated the long-term results of botulinum toxin (BoNT-A) in women with iOAB. METHODS: Patients treated with BoNT A from 2004 until 2009 were evaluated in a non-academic teaching hospital (Zuyderland MC, Heerlen, the Netherlands). All female patients with a follow-up of >5 years with idiopathic bladder dysfunction were included. All patients received 200 U of onabotulinum toxin-A in 20 intradetrusor injections. In some patients, we applied a dose adjustment for repeated injections. Patients were instructed how to use clean intermittent self-catheterization (CISC) before the treatment. We advised patients to commence CISC if post-void residual exceeded 150 ml. RESULTS: A total of 128 women were included. All patients had at least 5 year follow-up after their first injection. The mean follow-up was 97 (60-125) months. The mean age was 67 (46-88) years. Of all patients, 30 % were still on BoNT-A treatment at the last follow-up visit. Of the 70 % that discontinued treatment, 27 % had insufficient effect and 43 % had tolerability issues. Most patients discontinued treatment after the first (79 %) and second (19 %) injections. Only 2 % of patients discontinued treatment after more than two injections during follow-up. CONCLUSION: Intravesical BoNT-A is an effective treatment for women with idiopathic OAB. However, in time, almost two-thirds of patients in our study discontinued therapy. Most patients discontinue treatment after one or two injections and mainly due to tolerability issues. PMID- 27272313 TI - Assessing the effects of modality of surgery on postoperative weight loss in patients undergoing partial nephrectomy. AB - PURPOSE: To compare the early BMI changes postoperatively between patients undergoing open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN). METHODS: Patients undergoing open NSS for a single renal tumor between 2010 and 2013 were retrospectively selected for the study. These patients were matched with RPN patients based on preoperative BMI and tumor R.E.N.A.L nephrometry score (1:1 matching). RESULTS: A total of 568 patients (284 pairs) met our inclusion criteria. The median time to lowest BMI was comparable between the OPN and RPN groups (24 vs. 29 days; p = 0.7). The mean BMI preservation was lower for the OPN group (96.8 +/- 4.4 vs. 98.1 +/- 4.7 %). On multivariable analysis after controlling for age, CCI, gender, tumor size, nephrometry score, estimated blood loss, occurrence of major complications and preoperative renal function, the modality of surgery favoring the RPN approach and the occurrence of major complications remained significant predictors for BMI preservation after surgery. CONCLUSIONS: Occurrence of major complications is associated with weight loss after NSS. Minimally invasive NSS delivered by RPN had lower impact on BMI loss in patients undergoing the procedure compared to OPN. This finding further suggests that RPN delivers minimally invasive surgery beyond the boundaries of just smaller incision sites. PMID- 27272315 TI - Zinc-Responsive Necrolytic Acral Erythema in a Patient With Psoriasis: A Rare Case. AB - Necrolytic acral erythema (NAE) is a recently recognized dermatosis almost exclusively associated with hepatitis C virus (HCV) infection, and closely related to zinc deficiency. We present the case of a 60-year-old man with a history of psoriasis and chronic HCV infection, who developed new lesions of NAE extending from previous elephantine psoriatic plaques on bilateral lower legs. According to previous reports, resolution of NAE has been successfully achieved by treatment of the underlying HCV infection, or the use of oral zinc therapy. Our patient exhibited good response to zinc therapy. By reporting this case, we would like to raise the awareness of physicians to this unique acrally distributed dermatosis, which is distinct from psoriasis by its pathological feature of aggregated necrotic keratinocytes and its good response to zinc therapy rather than topical corticosteroids. PMID- 27272314 TI - Perceived live interaction modulates the developing social brain. AB - Although children's social development is embedded in social interaction, most developmental neuroscience studies have examined responses to non-interactive social stimuli (e.g. photographs of faces). The neural mechanisms of real-world social behavior are of special interest during middle childhood (roughly ages 7 13), a time of increased social complexity and competence coinciding with structural and functional social brain development. Evidence from adult neuroscience studies suggests that social interaction may alter neural processing, but no neuroimaging studies in children have directly examined the effects of live social-interactive context on social cognition. In the current study of middle childhood, we compare the processing of two types of speech: speech that children believed was presented over a real-time audio-feed by a social partner and speech that they believed was recorded. Although in reality all speech was prerecorded, perceived live speech resulted in significantly greater neural activation in regions associated with social cognitive processing. These findings underscore the importance of using ecologically-valid and interactive methods to understand the developing social brain. PMID- 27272316 TI - Multisystemic Sarcoidosis Presenting as Pretibial Leg Ulcers. AB - Sarcoidosis is a multisystemic disease of unknown etiology. Up to 30% of patients develop cutaneous manifestations, either specific or nonspecific. Ulcerating sarcoidosis leading to leg ulcers is a rare observation that may lead to confusions with other, more common types of chronic leg ulcers. We report the case of a 45-year-old female patient with chronic multisystemic sarcoidosis presenting with pretibial leg ulcers. Other etiology could be excluded. Histology revealed nonspecific findings. Therefore, the diagnosis of nonspecific leg ulcers in sarcoidosis was confirmed. Treatment consisted of oral prednisolone and good ulcer care. Complete healing was achieved within 6 months. Sarcoidosis is a rare cause of leg ulcers and usually sarcoid granulomas can be found. Our patient illustrates that even in the absence of sarcoid granulomas, leg ulcers can be due to sarcoidosis. PMID- 27272317 TI - Process and impact of an advance care planning intervention evaluated by bereaved surrogate decision-makers of dialysis patients. AB - BACKGROUND: Few studies have examined the process and impact of an advance care planning intervention experienced by surrogate decision-makers of dialysis patients. AIM: To explore the perspectives of the bereaved surrogates of dialysis patients on the process and impact of an advance care planning intervention and to compare the perceived impacts of the intervention between African Americans and Whites. DESIGN: Qualitative interviews and thematic analysis. SETTING/PARTICIPANTS: 24 bereaved surrogates of patients from outpatient dialysis centers were interviewed. Both patients and surrogates had been participants in a larger efficacy study and had received an advance care planning intervention, SPIRIT (Sharing Patient's Illness Representations to Increase Trust). RESULTS: Two themes related to the process of SPIRIT were as follows: (1) SPIRIT provided a welcome opportunity to think about and discuss topics that had been avoided and (2) SPIRIT helped patients and surrogates to share their feelings. Four themes of the SPIRIT's impact were as follows: (1) SPIRIT was an eye-opening experience, acquiring knowledge and understanding of the patient's illness and end-of-life care, (2) SPIRIT helped strengthen relationships between patients and surrogates, (3) SPIRIT helped surrogates feel prepared during the time leading up to end-of life decision-making, and (4) SPIRIT helped surrogates have peace of mind during and after actual end-of-life decision-making. Themes related to SPIRIT's impact on feeling prepared for end-of-life decision-making and the actual decision making experience more frequently occurred in African Americans than in Whites. CONCLUSION: Our data may help explain the beneficial effects of SPIRIT on surrogates, but future trials should include data on control surrogates' perspectives. PMID- 27272318 TI - Impressions That Last: Particularly Negative and Positive Experiences Reported by Parents Five Years after the End of a Child's Successful Cancer Treatment or Death. AB - OBJECTIVE: To describe the experience of parenting a child diagnosed with cancer by examining particularly negative and positive experiences reported by parents of childhood cancer survivors and parents of children lost to cancer. METHODS: 168 parents (88 mothers, 80 fathers) participated. Data were collected five years after the end of successful treatment or the child's death. The parents' experiences were identified by open-ended semi-structured questions about particularly negative and positive experiences of the child's cancer. An inductive approach was used in which the manifest verbal content of the answers was analysed using content analysis. RESULTS: The analysis revealed eight categories of negative experience (child late effects; distressing events; healthcare; impaired relationships; long-term psychological consequences; own reactions; surrounding institutions; the fact that the child got cancer) and seven categories of positive experience (healthcare; improved relationships; long term consequences for the child; personal development; support systems; treatment outcome; unexpected joy). The categories were related to past events or to the present situation. The findings indicate variations in experiences between parents of survivors and bereaved parents, and between fathers and mothers, as some experiences were only reported by parents of survivors and some experiences were only reported by mothers. CONCLUSIONS: The results highlight the importance of past and present events to parents, and accordingly the long-lasting impact of paediatric cancer on parents. The results also point to the wide range of negative as well as positive experiences involved in parenting a child diagnosed with cancer, and provide a comprehensive understanding of the overall experience for parents of children with cancer. Specifically, the findings give guidance to healthcare providers by illustrating the need to provide healthcare personnel with continuous training in communication skills, offering parents opportunities to meet other parents in the same situation and increasing the access to psychosocial supportive services and psychological care. PMID- 27272320 TI - Biography: Paul O'Brien, MD. PMID- 27272319 TI - Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination. AB - During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This 'nodal flow' is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo. PMID- 27272321 TI - Fast-Track in Bariatric and Metabolic Surgery: Feasibility and Cost Analysis Through a Matched-Cohort Study in a Single Centre. AB - BACKGROUND: Due to the rise in severe obesity in Western countries and the increase in bariatric surgery, enhanced recovery (ER) pathways should be developed and promoted. METHODS: A monocentric prospective series of 103 bariatric surgery patients managed with the ER pathway (group ER) was compared with a retrospective and immediately previous series of 103 patients managed with standard care (group CS). The aim of the present study was to assess and compare the differences in terms of mean postoperative length of stay (LOS), costs for surgery and recovery, and the differences in terms of complications, readmission, and reoperation rate in the short term between the ER and CS groups. RESULTS: The mean LOS was 4.18 days in group CS and 1.79 days in group ER (p < 0.0001). The mean operative time (OT) per patient was 190.20 min in the group CS and 133.54 min in the group ER, resulting in an average cost of 7272.57? per patient in group CS and 5424.09? per patient in group ER. The average recovery cost was 1809.94? for the group CS series and 775.07 for the group ER one. Overall complications (Clavien-Dindo up to II) occurred in 6 patients (5.8 %) in group CS and in 2 patients (1.9 %) in group ER (p = 0.149) and specific complications (Clavien-Dindo IIIb) occurred for 9 patients (8.7 %) in Group CS and for 14 patients (13.5 %) in group ER (p = 0.268) after hospital discharge within 1-month of follow-up. Twelve patients (11.5 %) in group CS and 13 (12.5 %) in group ER were readmitted after discharge (p = 0.831) within 1-month of follow-up; 8 patients (7.7 %) in group CS versus 9 patients (8.8 %) in group ER needed to be reoperated (p = 0.800) within 1-month follow-up. CONCLUSIONS: Enhanced recovery pathway reduces significantly LOS in bariatric surgical patients and shortens the mean OT of the procedure, with no significant differences in terms of surgical outcomes. Furthermore, recovery charges were lower and operative time was shorter allowing for procedural cost reduction. PMID- 27272322 TI - Erratum to: Vegfr3-CreER T2 mouse, a new genetic tool for targeting the lymphatic system. PMID- 27272323 TI - Kinetic barriers in the isomerization of substituted ureas: implications for computer-aided drug design. AB - Urea derivatives are ubiquitously found in many chemical disciplines. N,N' substituted ureas may show different conformational preferences depending on their substitution pattern. The high energetic barrier for isomerization of the cis and trans state poses additional challenges on computational simulation techniques aiming at a reproduction of the biological properties of urea derivatives. Herein, we investigate energetics of urea conformations and their interconversion using a broad spectrum of methodologies ranging from data mining, via quantum chemistry to molecular dynamics simulation and free energy calculations. We find that the inversion of urea conformations is inherently slow and beyond the time scale of typical simulation protocols. Therefore, extra care needs to be taken by computational chemists to work with appropriate model systems. We find that both knowledge-driven approaches as well as physics-based methods may guide molecular modelers towards accurate starting structures for expensive calculations to ensure that conformations of urea derivatives are modeled as adequately as possible. PMID- 27272324 TI - The Relationship Between Background Characteristics and Death Anxiety in Times of War: A Comparison Between Three Generations Arab and Jewish Families in Israel. AB - (a) To compare the levels of death anxiety between the Jewish and Arab population in Israel after the Second Lebanon War and the Casting Lead Operation. (b) To compare the levels of death anxiety between three families' generations: elderly parents, their adult children and their adult grandchildren and (c) to learn about the relationship between background characteristics and death anxiety in times of war. The sample included 172 trios of elderly parents (ages 65 and up), their middle aged children (ages 41-64) and, their young adult children (ages 20 40) living at the northern and southern of Israel. Three quarters of the participants were Jews and the others were Arabs (including Muslims, Christians and Druze). Participants answered a self-report questioner. Death anxiety levels were measured by the Carmel and Mutran's instrument (1999). In general, the highest levels of death anxiety were found among the elderly parents (p < 0.01). Regarding the nationality and the gender variables, the highest levels of death anxiety were found among the adult Jewish daughters' group (p < 0.001). Nationality was found to be the most contributive variable for predicting death anxiety levels among the three generations; the sense of mastery was the second contributor, to predict death anxiety levels among the three generations' participants. Elderly population, Arab population and women, are at high risk to suffer from high levels of death anxiety in times of war in Israel. Special attention should be given to this population groups. PMID- 27272325 TI - British Dietetic Association systematic review and evidence-based practice guidelines for the dietary management of irritable bowel syndrome in adults (2016 update). AB - BACKGROUND: The first British Dietetic Association (BDA) guidelines for the dietary management of irritable bowel syndrome (IBS) in adults were published in 2012. Subsequently, there has been a wealth of new research. The aim of this work was to systematically review the evidence for the role of diet in the management of IBS and to update the guidelines. METHODS: Twelve questions relating to diet and IBS were defined based on review of the previous guideline questions, current evidence and clinical practice. Chosen topics were on healthy eating and lifestyle (alcohol, caffeine, spicy food, elimination diets, fat and fluid intakes and dietary habits), milk and dairy, dietary fibre, fermentable carbohydrates, gluten, probiotics and elimination diets/food hypersensitivity. Data sources were CINAHL, Cochrane Register of Controlled Trials, Embase, Medline, Scopus and Web of Science up to October 2015. Studies were assessed independently in duplicate using risk of bias tools specific to each included study based on inclusion and exclusion criteria for each question. National Health and Medical Research Council grading evidence levels were used to develop evidence statements and recommendations, in accordance with Practice-based Evidence in Nutrition Global protocol used by the BDA. RESULTS: Eighty-six studies were critically appraised to generate 46 evidence statements, 15 clinical recommendations and four research recommendations. The IBS dietary algorithm was simplified to first-line (healthy eating, provided by any healthcare professional) and second-line [low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) to be provided by dietitian] dietary advice. CONCLUSIONS: These guidelines provide updated comprehensive evidence based details to achieve the successful dietary management of IBS in adults. PMID- 27272326 TI - Stepping-stones and dispersal flow: establishment of a meta-population of Milu (Elaphurus davidianus) through natural re-wilding. AB - The Milu (Pere David's deer, Elaphurus davidianus) became extinct in China in the early 20(th) century but was reintroduced to the country. The reintroduced Milu escaped from a nature reserve and dispersed to the south of the Yangtze River. We monitored these accidentally escaped Milu from 1995 to 2012. The escaped Milu searched for vacant habitat patches as "stepping stones" and established refuge populations. We recorded 122 dispersal events of the escaped Milu. Most dispersal events occurred in 1998, 2003, 2006 and 2010. Milu normally disperse in March, July and November. Average dispersal distance was 14.08 +/- 9.03 km, with 91.41% shorter than 25 km. After 5 generations, by the end of 2012, 300 wild Milu were scattered in refuge populations in the eastern and southern edges of the Dongting Lake. We suggest that population density is the ultimate cause for Milu dispersal, whereas floods and human disturbance are proximate causes. The case of the Milu shows that accidentally escaped animals can establish viable populations; however, the dispersed animals were subject to chance in finding "stepping stones". The re-wilded Milu persist as a meta-population with sub populations linked by dispersals through marginal habitats in an anthropogenic landscape. PMID- 27272327 TI - Bacteraemic urinary tract infections may mimic respiratory infections: a nested case-control study. AB - Daily practice suggests that respiratory signs may be observed in bacteraemic urinary infections (BUI). Our objective was to search for an association between the presence of respiratory symptoms and the bacteraemic nature of urinary tract infections (UTI). A nested case-control study was carried out based on our computerised dashboard from January 2011 to June 2015. Cases were defined as patients with a BUI due to Enterobacteriaceae species, identified in blood and urine cultures. Controls had fever and a positive urinary sample but sterile blood cultures (NBUI) and a final diagnosis of urinary infection. Patients from the BUI group were 1:1 matched to the NBUI group according to four parameters: age, gender, cardiovascular and pulmonary comorbid conditions. Subjects with cognitive impairment limiting clinical accuracy and those with healthcare associated infections were excluded. We compared systematically recorded respiratory and urinary symptoms between groups: signs on auscultation, dyspnoea, chest pain, cough and sputum, dysuria with burning, pollakiuria, flank or costovertebral angle tenderness and ischuria. One hundred BUI were compared to 100 NBUI, both groups exhibiting a similar rate for all considered comorbid conditions. In the BUI group, 58 % showed at least one respiratory sign vs. 20 % in the NBUI group, p < 0.001, while urinary signs were less frequent: 54 % vs. 71 %, p = 0.013. In the multivariate analysis, BUI was associated with the presence of abnormal pulmonary auscultation [adjusted odds ratio (AOR), 5.91; p < 0.001] and a trend towards less urinary symptoms (AOR, 1.58; p = 0.058). Patients with BUI presented with significantly more respiratory signs, which overshadowed urinary symptoms, compared to those with non-bacteraemic UTI. Such observations impact clinical decision-making. PMID- 27272328 TI - Breeding Guild Determines Frog Distributions in Response to Edge Effects and Habitat Conversion in the Brazil's Atlantic Forest. AB - Understanding the response of species with differing life-history traits to habitat edges and habitat conversion helps predict their likelihood of persistence across changing landscape. In Brazil's Atlantic Forest, we evaluated frog richness and abundance by breeding guild at four distances from the edge of a reserve: i) 200 m inside the forest, ii) 50 m inside the forest, iii) at the forest edge, and iv) 50 m inside three different converted habitats (coffee plantation, non-native Eucalyptus plantation, and abandoned pastures, hereafter matrix types). By sampling a dry and a wet season, we recorded 622 individual frogs representing 29 species, of which three were undescribed. Breeding guild (i.e. bromeliad, leaf-litter, and water-body breeders) was the most important variable explaining frog distributions in relation to edge effects and matrix types. Leaf-litter and bromeliad breeders decreased in richness and abundance from the forest interior toward the matrix habitats. Water-body breeders increased in richness toward the matrix and remained relatively stable in abundance across distances. Number of large trees (i.e. DBH > 15 cm) and bromeliads best explained frog richness and abundance across distances. Twenty species found in the interior of the forest were not found in any matrix habitat. Richness and abundance across breeding guilds were higher in the rainy season but frog distributions were similar across the four distances in the two seasons. Across matrix types, leaf-litter species primarily used Eucalyptus plantations, whereas water-body species primarily used coffee plantations. Bromeliad breeders were not found inside any matrix habitat. Our study highlights the importance of primary forest for bromeliad and leaf-litter breeders. We propose that water-body breeders use edge and matrix habitats to reach breeding habitats along the valleys. Including life-history characteristics, such as breeding guild, can improve predictions of frog distributions in response to edge effect and matrix types, and can guide more effective management and conservation actions. PMID- 27272329 TI - [Posterior reversible encephalopathy syndrome]. AB - Posterior reversible encephalopathy syndrome refers to a neurological disorder characterized by headache, disorders of consciousness, visual disturbances, epileptic seizures, and subcortical vasogenic edema. About two thirds of patients develop neurological symptoms, which are associated with blood pressure fluctuations. One hypothesis is that hypertensive episodes cause autoregulatory failure, and values above the upper limit of cerebral autoregulation result in a breakthrough followed by hyperperfusion and blood-brain barrier dysfunction. In another hypothesis, endothelial dysfunction triggered by numerous factors including preeclampsia, immunosuppressive agents, chemotherapeutics, sepsis, or autoimmune disorders is thought to be the key pathomechanism. Endo- or exogenic toxic agents including pharmacological substances, cytokines, or bacterial toxins are supposed to trigger endothelial activation and dysfunction resulting in the release of vasoconstrictors, pro-inflammatory mediators, and vascular leakage. Diagnosis is usually based on clinical and neuroimaging findings that frequently show a bilateral, symmetric, and parietooccipital pattern. However, the diagnosis can often only be confirmed during the course of disease after excluding important differential diagnoses. Currently, there is no specific treatment available. Lowering of arterial blood pressure and eliminating the underlying cause usually leads to an improvement of clinical and neuroradiological findings. Admission to a critical care unit is required in about 40 % of patients due to complicating conditions including status epilepticus, cerebral vasoconstriction, ischemia, or intracerebral hemorrhage. Prognosis is favorable; in the majority of patients neurological deficits and imaging findings resolve completely. PMID- 27272330 TI - Physical Health Screenings Among African-American Church and Community Members. AB - This study sought to identify characteristics, including religiosity, related to having received health screenings among persons who attend African-American churches or receive church-based community outreach services. A sample of 602 was recruited during two phases as part of a larger project. Blood pressure, cholesterol, and blood glucose screenings were the most frequently reported screenings ever and in the last 12 months. Although religiosity was significantly related to several of the health screenings in bivariate analysis, it is not a predictor of health screenings in multivariate analyses. Innovative strategies are needed to promote screenings such as church-based health fairs. PMID- 27272331 TI - Similarities and Differences Between Yoruba Traditional Healers (YTH) and Native American and Canadian Healers (NACH). AB - Indigenous people of the world have used the services of medicine men and traditional healers from time immemorial. According to the World Health Organization, 80 % of the world's populations consult traditional healers. With an emerging globalization of health services in the world, there is a need for western mental health practitioners to learn and understand the practices of indigenous healers across the globe. This paper will not only highlight the similarities and differences between Yoruba traditional healers of Western Nigeria and Native American and First Nation Canadian traditional healers, but it will also allow practitioners to gain clearer perspectives of indigenous clients from Yoruba land and those from the United States of America and Canada. This ultimately will inform culturally sensitive clinical practice with these populations. PMID- 27272332 TI - Increased Risk of Dementia in Patients with Tension-Type Headache: A Nationwide Retrospective Population-Based Cohort Study. AB - PURPOSE: The association between primary headaches, including tension-type headache (TTH) as one of the most common primary headache disorders, and dementia remains controversial. In this nationwide, population-based, retrospective, cohort study, we explored the potential association between TTH and dementia and examined sex, age, and comorbidities as risk factors for dementia. METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD) claims data, the sample included 13908 subjects aged >=20 years with newly-diagnosed TTH in 2000 2006. The non-TTH group included 55632 randomly selected sex- and age-matched TTH free individuals. All subjects were followed until dementia diagnosis, death, or the end of 2011. Patients with dementia, including vascular and non-vascular (including Alzheimer's) subtypes, were identified using International Classification of Diseases Ninth Revision, Clinical Modification codes. Multivariate Cox proportional hazards regression models were used to assess the risk of dementia and dementia-associated risk factors, such as migraine and other medical comorbidities. RESULTS: During the average follow-up of 8.14 years, the incidence density rates of dementia were 5.30 and 3.68/1,000 person-years in the TTH and non-TTH groups, respectively. Compared with the non-TTH group, the risks of dementia were 1.25 (95% confidence interval [CI], 1.11-1.42) and 1.13 (95% CI, 1.01-1.27) times higher in the women and >65-year-old TTH group, respectively. TTH patients with comorbidities had a higher risk of dementia. TTH patients had a greater risk of non-vascular dementia (hazard ratio, 1.21; 95% CI, 1.09-1.34) than the non-TTH group. CONCLUSION: TTH patients have a future risk of dementia, indicating a potentially linked disease pathophysiology that warrants further study. The association between TTH and dementia is greater in women, older adults, and with comorbidities. Clinicians should be aware of potential dementia comorbidity in TTH patients. PMID- 27272333 TI - A Cytochrome P450-Mediated Intramolecular Carbon-Carbon Ring Closure in the Biosynthesis of Multidrug-Resistance-Reversing Lathyrane Diterpenoids. AB - The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids with potential applications in the treatment of pain, HIV and cancer. We report here a gene cluster from Jatropha curcas that contains the genes required to convert geranylgeranyl pyrophosphate into a number of diterpenoids, including the lathyranes jolkinol C and epi-jolkinol C. The conversion of casbene to the lathyranes involves an intramolecular carbon-carbon ring closure. This requires the activity of two cytochrome P450s that we propose form a 6-hydroxy-5,9-diketocasbene intermediate, which then undergoes an aldol reaction. The discovery of the P450 genes required to convert casbene to lathyranes will allow the scalable heterologous production of these potential anticancer drugs, which can often only be sourced in limited quantities from their native plant. PMID- 27272334 TI - Safe use of high intakes of folic acid: research challenges and paths forward. AB - Adequate folic acid intake is an effective dietary-based prevention tool for reducing the risk of neural tube defects. Achieving adequate intake for the prevention of neural tube defects frequently requires the consumption of foods fortified with folic acid and/or the use of folic acid-containing dietary supplements. To date, research on the potential for adverse effects of high intakes of folic acid has been limited. Without such research, it is difficult to define a value for high intake. In May 2015, an expert panel was tasked with examining the available scientific literature and making research recommendations within 4 general categories of potential folate-related adverse health effects: cancer, cognition in conjunction with vitamin B12 deficiency, hypersensitivity related outcomes, and thyroid and diabetes-related disorders. This article summarizes the expert panel's conclusions, outlines the challenges faced when reviewing the literature, and examines some of the panel's recommendations for research. PMID- 27272337 TI - Correction: Protecting medicine's wild pharmacy. PMID- 27272335 TI - Quinolone-1-(2H)-ones as hedgehog signalling pathway inhibitors. AB - A series of quinolone-2-(1H)-ones derived from the Ugi-Knoevenagel three- and four-component reaction were prepared exhibiting low micromolar cytotoxicity against a panel of eight human cancer cell lines known to possess the Hedgehog Signalling Pathway (HSP) components, as well as the seminoma TCAM-2 cell line. A focused SAR study was conducted and revealed core characteristics of the quinolone-2-(1H)-ones required for cytotoxicity. These requirements included a C3 tethered indole moiety, an indole C5-methyl moiety, an aliphatic tail or an ester, as well as an additional aromatic moiety. Further investigation in the SAG activated Shh-LIGHT2 cell line with the most active analogues: 2-(3-cyano-2-oxo-4 phenylquinolin-1(2H)-yl)-2-(1-methyl-1H-indol-3-yl)-N-(pentan-2-yl)acetamide (5), 2-(3-cyano-2-oxo-4-phenylquinolin-1(2H)-yl)-2-(5-methyl-1H-indol-3-yl)-N-(pentan 2-yl)acetamide (23) and ethyl (2-(3-cyano-2-oxo-4-phenylquinolin-1(2H)-yl)-2-(5 methyl-1H-indol-3-yl)acetyl)glycinate (24) demonstrated a down regulation of the HSP via a reduction in Gli expression, and in the mRNA levels of Ptch1 and Gli2. Analogues 5, 23 and 24 returned in cell inhibition values of 11.6, 2.9 and 3.1 MUM, respectively, making this new HSP-inhibitor pharmacophore amongst the most potent non-Smo targeted inhibitors thus far reported. PMID- 27272338 TI - Refractory Hypotension and "Ventricular Fibrillation" With Large U Waves After Overdose. PMID- 27272339 TI - Overcoming the framing problem-a critical-ethical perspective on the need to integrate social sciences and humanities and stakeholder contributions in EURATOM radiation protection research. AB - This paper introduces the 'framing problem' as the problem of the limited potential of critical reflection on the societal justification and use of nuclear energy technology as a contribution to European radiation protection research, given that the research is itself driven by EURATOM's pro-nuclear political position. The idea is that the problem of policy framing could in principle be 'overcome' by the integration of social sciences and humanities and stakeholder contributions in that research, taking into account that this approach could help to raise critical awareness with the involved researchers and policy makers of the issues of fairness of risk justification in society and of the consequences thereof for nuclear energy policy and policy-supportive research itself. PMID- 27272340 TI - The association of ideal cardiovascular health with incident type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis. AB - AIMS/HYPOTHESIS: Levels of ideal cardiovascular health (ICH) and incident type 2 diabetes mellitus have not been examined in a multiethnic population. We assessed the total and race/ethnicity-specific incidence of diabetes based on American Heart Association (AHA) ICH components. METHODS: Incident diabetes was assessed among 5341 participants in the Multi-Ethnic Study of Atherosclerosis without prevalent diabetes between 2002 and 2012. ICH components (total cholesterol, BP, dietary intake, tobacco use, physical activity and BMI) were assessed at baseline and participants were categorised as having ideal, intermediate or poor cardiovascular health, as defined by the AHA 2020 impact goals. We developed a scoring system based on the number of ICH components (0-1 'poor', 2-3 'intermediate', and >=4 'ideal'). HRs were calculated using Cox models. RESULTS: During a median follow-up of 11.1 years, we identified 587 cases of incident diabetes. After multivariable adjustment, participants with 2-3 and >=4 ICH components vs 0-1 components had a 34% lower (HR 0.66; 95% CI 0.54, 0.80) and a 75% lower (HR 0.25; 95% CI 0.18, 0.35) diabetes incidence, respectively. There were significant differences by race/ethnicity: African-American and Hispanic American participants with >=4 ICH components had diabetes incidence rates per 1000 person-years of 5.6 (95% CI 3.1, 10.1) and 10.5 (95% CI 6.7, 16.4), respectively, compared with 2.2 (95% CI 1.3, 3.7) among non-Hispanic white Americans. CONCLUSIONS/INTERPRETATION: Meeting an increasing number of AHA 2020 impact goals for dietary intake, physical activity, smoking, BP, cholesterol and BMI was associated with a dose-dependent lower risk of diabetes with significant variation by race/ethnicity. PMID- 27272341 TI - Abnormal regional homogeneity as potential imaging biomarker for psychosis risk syndrome: a resting-state fMRI study and support vector machine analysis. AB - Subjects with psychosis risk syndrome (PRS) have structural and functional abnormalities in several brain regions. However, regional functional synchronization of PRS has not been clarified. We recruited 34 PRS subjects and 37 healthy controls. Regional homogeneity (ReHo) of resting-state functional magnetic resonance scans was employed to analyze regional functional synchronization in these participants. Receiver operating characteristic curves and support vector machines were used to detect whether abnormal regional functional synchronization could be utilized to separate PRS subjects from healthy controls. We observed that PRS subjects showed significant ReHo decreases in the left inferior temporal gyrus and increases in the right inferior frontal gyrus and right putamen compared with the controls. No correlations between abnormal regional functional synchronization in these brain regions and clinical characteristics existed. A combination of the ReHo values in the three brain regions showed sensitivity, specificity, and accuracy of 88.24%, 91.89%, and 90.14%, respectively, for discriminating PRS subjects from healthy controls. We inferred that abnormal regional functional synchronization exists in the cerebrum of PRS subjects, and a combination of ReHo values in these abnormal regions could be applied as potential image biomarker to identify PRS subjects from healthy controls. PMID- 27272342 TI - Oxytocin, trust and very late-onset schizophrenia-like psychosis. PMID- 27272347 TI - Challenges to polycentric governance of an international development project tackling land degradation in Swaziland. AB - To effectively address the drivers and impacts of land degradation requires polycentric governance systems that facilitate international development projects (IDPs). This paper analyses an IDP aiming to reduce land degradation in Swaziland. A longitudinal-style qualitative approach draws on repeat household surveys, semi-structured interviews and focus groups. We aim to identify the changes that have taken place since the departure of the IDP funders, and the subsequent dynamics between stakeholders. We: (1) chart the evolution of the institutional structures and processes of the IDP; and (2) assess community perceptions of IDP outcomes. Lack of meaningful participation at various stages of the PMC caused the project to lose momentum following the departure of the funders. We discuss these findings in relation to a polycentric approach, and identify how multi-stakeholder IDP can be facilitated as part of wider polycentric governance approaches to inform policies to combat land degradation within Swaziland and more widely. PMID- 27272348 TI - The sustainability of changes in agricultural technology: The carbon, economic and labour implications of mechanisation and synthetic fertiliser use. AB - New agricultural technologies bring multiple impacts which are hard to predict. Two changes taking place in Indian agriculture are a transition from bullocks to tractors and an associated replacement of manure with synthetic fertilisers. This paper uses primary data to model social, environmental and economic impacts of these transitions in South India. It compares ploughing by bullocks or tractors and the provision of nitrogen from manure or synthetic urea for irrigated rice from the greenhouse gas (GHG), economic and labour perspective. Tractors plough nine times faster than bullocks, use substantially less labour, with no significant difference in GHG emissions. Tractors are twice as costly as bullocks yet remain more popular to hire. The GHG emissions from manure-N paddy are 30 % higher than for urea-N, largely due to the organic matter in manure driving methane emissions. Labour use is significantly higher for manure, and the gender balance is more equal. Manure is substantially more expensive as a source of nutrients compared to synthetic nutrients, yet remains popular when available. This paper demonstrates the need to take a broad approach to analysing the sustainability impacts of new technologies, as trade-offs between different metrics are common. PMID- 27272349 TI - Novel Gene Expression Signature Predictive of Clinical Recurrence After Radical Prostatectomy in Early Stage Prostate Cancer Patients. AB - BACKGROUND: Current clinical tools have limited accuracy in differentiating patients with localized prostate cancer who are at risk of recurrence from patients with indolent disease. We aimed to identify a gene expression signature that jointly with clinical variables could improve upon the prediction of clinical recurrence after RP for patients with stage T2 PCa. METHODS: The study population includes consented patients who underwent a radical retropubic prostatectomy (RP) and bilateral pelvic lymph node dissection at the University of Southern California in the PSA-era (1988-2008). We used a nested case-control study of 187 organ-confined patients (pT2N0M0): 154 with no recurrence ("controls") and 33 with clinical recurrence ("cases"). RNA was obtained from laser capture microdissected malignant glands representative of the overall Gleason score of each patient. Whole genome gene expression profiles (29,000 transcripts) were obtained using the Whole Genome DASL HT platform (Illumina, Inc). A gene expression signature of PCa clinical recurrence was identified using stability selection with elastic net regularized logistic regression. Three existing datasets generated with the Affymetrix Human Exon 1.0ST array were used for validation: Mayo Clinic (MC, n = 545), Memorial Sloan Kettering Cancer Center (SKCC, n = 150), and Erasmus Medical Center (EMC, n = 48). The areas under the ROC curve (AUCs) were obtained using repeated fivefold cross-validation. RESULTS: A 28-gene expression signature was identified that jointly with key clinical variables (age, Gleason score, pre-operative PSA level, and operation year) was predictive of clinical recurrence (AUC of clinical variables only was 0.67, AUC of clinical variables, and 28-gene signature was 0.99). The AUC of this gene signature fitted in each of the external datasets jointly with clinical variables was 0.75 (0.72-0.77) (MC), 0.90 (0.86-0.94) (MSKCC), and 0.82 (0.74-0.91) (EMC), whereas the AUC for clinical variables only in each dataset was 0.72 (0.70-0.74), 0.86 (0.82-0.91), and 0.76 (0.67-0.85), respectively. CONCLUSIONS: We report a novel gene-expression based classifier identified using agnostic approaches from whole genome expression profiles that can improve upon the accuracy of clinical indicators to stratify early stage localized patients at risk of clinical recurrence after RP. Prostate 76:1239-1256, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272350 TI - Dynamical control on helicity of electromagnetic waves by tunable metasurfaces. AB - Manipulating the polarization states of electromagnetic (EM) waves, a fundamental issue in optics, attracted intensive attention recently. However, most of the devices realized so far are either too bulky in size, and/or are passive with only specific functionalities. Here we combine theory and experiment to demonstrate that, a tunable metasurface incorporating diodes as active elements can dynamically control the reflection phase of EM waves, and thus exhibits unprecedented capabilities to manipulate the helicity of incident circular polarized (CP) EM wave. By controlling the bias voltages imparted on the embedded diodes, we demonstrate that the device can work in two distinct states. Whereas in the "On" state, the metasurface functions as a helicity convertor and a helicity hybridizer within two separate frequency bands, it behaves as a helicity keeper within an ultra-wide frequency band in the "Off" state. Our findings pave the way to realize functionality-switchable devices related to phase control, such as frequency-tunable subwavelength cavities, anomalous reflectors and even holograms. PMID- 27272351 TI - Continuous subcutaneous insulin infusion versus multiple daily injections of insulin for pregnant women with diabetes. AB - BACKGROUND: Diabetes results in a rise in blood glucose above normal physiological levels; if untreated this may cause damage to many systems including the cardiovascular and renal systems. Pregnancy increases resistance to insulin action; for those women who have pre-gestational diabetes, this results in an increasing insulin requirement. There are several methods of administering insulin. Conventionally, insulin has been administered subcutaneously, formally referred to as intensive conventional treatment, but now more usually referred to as multiple daily injections (MDI). An alternative method of insulin administration is the continuous subcutaneous insulin infusion pump (CSII). OBJECTIVES: To compare CSII with MDI of insulin for pregnant women with pre existing and gestational diabetes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised trials comparing CSII with MDI for pregnant women with diabetes. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies and two review authors extracted data. Disagreements were resolved through discussion with the third author. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included five single-centre trials (undertaken in Italy) with 153 women and 154 pregnancies in this review.There were no clear differences in the primary outcomes reported between CSII and MDI in the included trials: caesarean section (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.66 to 1.77; three trials, 71 women, evidence graded very low), large-for-gestational age (RR 4.15, 95% CI 0.49 to 34.95; three trials, 73 infants; evidence graded very low), and perinatal mortality (RR 2.33, 95% CI 0.38 to 14.32; four trials, 83 infants, evidence graded very low). Other primary outcomes were not reported in these trials (hypertensive disorders of pregnancy, development of type 2 diabetes, composite outcome of serious neonatal outcomes, and neurosensory disability).There was no clear evidence of differences in the maternal secondary outcomes: maternal weight gain during pregnancy, 24 hour mean blood glucose in each trimester, mean maternal HbA1c in each trimester, maternal hypoglycaemia, and maternal hyperglycaemia. The included studies did not report several GRADE outcomes: perineal trauma, return to pre-pregnancy weight, postnatal depression, induction of labour. Many maternal secondary outcomes were also not reported.In two trials, including a total of 61 infants, CSII was associated with an increase in mean birthweight compared with MDI (mean difference (MD) 220.56 g, 95% CI -2.09 g to 443.20 g; P = 0.05). However, the large CI including anything from a small reduction to an increase in mean birthweight and the lack of a difference in macrosomia rate (RR 3.20, CI 0.14 to 72.62; two trials, 61 infants) suggests uncertainty. Large-for-gestational age (see above), andsmall-for-gestational age also suggests uncertainty of effect. No significant differences were found in: gestation at delivery, preterm birth < 37 weeks' gestation, preterm birth < 32 weeks' gestation, neonatal hypoglycaemia (evidence graded very low), respiratory distress syndrome, neonatal hyperbilirubinaemia, and fetal anomaly. There were no data reported on many important infant outcomes, including the GRADE outcomes adiposity and diabetes. There was no follow-up of infants in childhood or adulthood, so longer-term outcomes were not reported.The only outcome reported for use of health service resources wasmaternal days hospitalised, which did not show a difference between groups in the small number of women included (MD 9.40, CI -6.04 to 24.84; one trial, 10 women).The methods used by the trials were poorly reported, for example although blinding of participants and clinicians regarding intervention allocation is impossible, it is possible to blind assessors and this along with other aspects of trial methods was not reported, which means that the trials are at an unclear or high risk of bias. We do not know if the women who participated were representative, and therefore if the results can be generalised. Most GRADE outcomes were not reported. For the GRADE outcomes that were reported, our assessment was that the evidence is very low quality (caesarean section, large-for-gestational age, perinatal mortality, andneonatal hypoglycaemia). This was due to design limitations in the included trials, small sample sizes in the trials contributing data, wide CIs crossing both the line of no effect and the line of appreciable benefit and/or harm, and often few events. We are therefore uncertain whether CSII or MDI improves outcomes for pregnant women with diabetes and their infants, and the results of further studies may differ substantially from those presented in this review. AUTHORS' CONCLUSIONS: There is no evidence to support the use of one particular form of insulin administration over another for pregnant women with diabetes. There are only a small number of trials appropriate for meta-analysis, a small number of women included and questionable generalisability of the trial population.Pump technology has progressed since these trials were undertaken. Well-designed randomised trials are required to evaluate comparisons such as patch pumps against MDI and more conventional CSII against MDI. These trials should be adequately powered to assess the effect of interventions, and report the core set of outcomes used in Cochrane reviews of diabetes in pregnancy. Trials to assess the effects of pumps on birthweight and macrosomia rates are needed. It would be beneficial for future trials to undertake longer-term follow up of participants and their infants, assess women's preferences, and conduct an economic evaluation. PMID- 27272352 TI - Giant Panda Maternal Care: A Test of the Experience Constraint Hypothesis. AB - The body condition constraint and the experience condition constraint hypotheses have both been proposed to account for differences in reproductive success between multiparous (experienced) and primiparous (first-time) mothers. However, because primiparous mothers are typically characterized by both inferior body condition and lack of experience when compared to multiparous mothers, interpreting experience related differences in maternal care as support for either the body condition constraint hypothesis or the experience constraint hypothesis is extremely difficult. Here, we examined maternal behaviour in captive giant pandas, allowing us to simultaneously control for body condition and provide a rigorous test of the experience constraint hypothesis in this endangered animal. We found that multiparous mothers spent more time engaged in key maternal behaviours (nursing, grooming, and holding cubs) and had significantly less vocal cubs than primiparous mothers. This study provides the first evidence supporting the experience constraint hypothesis in the order Carnivora, and may have utility for captive breeding programs in which it is important to monitor the welfare of this species' highly altricial cubs, whose survival is almost entirely dependent on receiving adequate maternal care during the first few weeks of life. PMID- 27272353 TI - Quality Control and Complication Screening Programme of Chinese Medicinal Drugs at the First German Hospital of Traditional Chinese Medicine - A Retrospective Analysis. AB - BACKGROUND: The use of drugs derived from plants is a cornerstone of Traditional Chinese Medicine (TCM). Yet, too little is known about risk and safety of Chinese medicinal drugs (CMD). Therefore, the TCM hospital Bad Kotzting has developed a quality control and complication screening programme in order to ensure a safe administration of TCM drugs to their patients. METHODS: All Chinese medicinal drugs delivered to the hospital between September 1, 2012 and December 31, 2013 entered the quality control program and were screened for microbial contamination, aflatoxin, pesticides and heavy metals. A routinely applied complication screening programme monitored liver enzymes in all patients. Case causality assessment by CIOMS scale and identification of admitted herbs were conducted. Additionally, side effects of patients were identified by a routinely performed web-based documentation system. RESULTS: In 5 of 23 investigated samples (21.7%) the initial testing showed microbial contamination (2), pesticide (2) and heavy metals (1). The drugs were tested for authenticity and adulterations, respectively. All 994 patients (mean age 52.6 years; 72.6% female) admitted were available for analysis. 448 (45.1%) of all patients reported having perceived at least one side effect of treatment. They experienced mainly gastrointestinal symptoms (13.6%), neurovegetative symptoms (10.8 %), temporary deteriorations of pain (8.8%), diarrhoea (5.9%), nausea (1.6%) and vomiting (0.5%). Further, 6 patients with a more than 2-fold elevation (compared to maximum normal value or elevated admission values) of ALT were found in the systematic laboratory control with a non-conclusive causality assessment for TCM drugs. CONCLUSION: Approximate incidence rates and analysed drugs associated with liver damage revealed a low rate of liver injury. Patients should be informed of the gastrointestinal symptoms caused by and potential hepatotoxicity of TCM herbs. PMID- 27272354 TI - Even wars have rules. PMID- 27272355 TI - [Not Available]. PMID- 27272356 TI - [Not Available]. PMID- 27272357 TI - [Not Available]. PMID- 27272358 TI - [Not Available]. PMID- 27272359 TI - [Not Available]. PMID- 27272360 TI - [Not Available]. PMID- 27272361 TI - [Not Available]. PMID- 27272362 TI - [Not Available]. PMID- 27272363 TI - [Reductions in cardiac death is not due to statins]. PMID- 27272364 TI - [Protein intolerance - a neglected health problem]. PMID- 27272365 TI - [Specialist training for physicians - clear responsibility, better quality]. PMID- 27272366 TI - [Subsidizing of progestin contraceptives - on a collision course with biology?]. PMID- 27272367 TI - [Not Available]. PMID- 27272368 TI - Paperless migrants and Norwegian general practitioners. AB - BACKGROUND: In Norway, the rights of paperless migrants are restricted. We wished to investigate the extent to which Norwegian general practitioners give treatment to this group and their grounds for doing so, as well as to identify the health problems that were presented. MATERIAL AND METHOD: In 2010, an online questionnaire was distributed to 3 994 general practitioners who were members of the Norwegian Medical Association. RESULTS: Altogether 1 027 GPs responded. Of these, 237 (23 %) reported to have treated paperless migrants. Mental problems, pregnancy-related issues and respiratory ailments were the most frequently reported reasons for contact. Of the 237 GPs who reported to have treated paperless migrants, altogether 166 (70 %) stated that they would continue to receive these patients. INTERPRETATION: The fact that most of the GPs who had treated paperless migrants would continue to receive this patient group and thus provide health services beyond this group's entitlements, we regard as a wish to comply with the Code of Ethics for Norwegian doctors. PMID- 27272369 TI - ["Sulfonamide allergy" - which drugs must patients avoid?]. AB - Allergic reactions to sulfonamide antibiotics are common. A number of other drugs (for example diuretics, anti-diabetic drugs, cyclooxygenase-2 inhibitors and triptans) are also chemically speaking sulphonamides, and many of these are considered to be contraindicated in patients who have experienced an allergic reaction to sulfonamide antibiotics. What is the risk of allergic cross reactivity between different sulfonamides and to what extent must this be taken into account in clinical practice? PMID- 27272370 TI - [Medication adherence and monitoring of antihypertensive treatment]. AB - Lack of adherence to medication may be the explanation for unsatisfactory drug efficacy and is often misinterpreted as resistance to treatment. When encountering patients with persistent high blood pressure despite antihypertensive treatment, it is therefore important to discover whether they are actually taking their medication. This article aims to provide an updated overview of methods of revealing and monitoring medication adherence. The article is based on non-systematic literature searches in PubMed and on the senior authors' own clinical experience. PMID- 27272371 TI - A methadone user with anaemia, skeletal pain and altered appearance. PMID- 27272372 TI - [Strategies for BCG vaccination 1947 - 94]. AB - The tuberculosis reform of 1947 stipulated a clear responsibility of the state to combat tuberculosis. This entailed sanctions directed at individuals, as well as compulsory vaccination. Universal vaccination was to be achieved through extensive information work that emphasised the responsibility of the individual. The decline in the disease, the dawning of human rights thinking and the decline of professional boards in public administration help to explain the downgrading of compulsory vaccination over time. PMID- 27272373 TI - [A medical education for the patient - lessons from a sick youth]. PMID- 27272374 TI - [Prospective and retrospective]. PMID- 27272375 TI - [Not Available]. PMID- 27272377 TI - [Not Available]. PMID- 27272378 TI - [Not Available]. PMID- 27272379 TI - [Not Available]. PMID- 27272380 TI - [Not Available]. PMID- 27272381 TI - [Not Available]. PMID- 27272383 TI - Regulating the expression of therapeutic transgenes by controlled intake of dietary essential amino acids. AB - Widespread application of gene therapy will depend on the development of simple methods to regulate the expression of therapeutic genes. Here we harness an endogenous signaling pathway to regulate therapeutic gene expression through diet. The GCN2-eIF2alpha signaling pathway is specifically activated by deficiencies in any essential amino acid (EAA); EAA deficiency leads to rapid expression of genes regulated by ATF4-binding cis elements. We found that therapeutic genes under the control of optimized amino acid response elements (AAREs) had low basal expression and high induced expression. We applied our system to regulate the expression of TNFSF10 (TRAIL) in the context of glioma therapy and found that intermittent activation of this gene by EEA-deficient meals retained its therapeutic efficacy while abrogating its toxic effects on normal tissue. The GCN2-eIF2alpha pathway is expressed in many tissues, including the brain, and is highly specific to EAA deficiency. Our system may be particularly well suited for intermittent regulation of therapeutic transgenes over short or long time periods. PMID- 27272384 TI - Genome-wide analysis reveals specificities of Cpf1 endonucleases in human cells. AB - Programmable clustered regularly interspaced short palindromic repeats (CRISPR) Cpf1 endonucleases are single-RNA-guided (crRNA) enzymes that recognize thymidine rich protospacer-adjacent motif (PAM) sequences and produce cohesive double stranded breaks (DSBs). Genome editing with CRISPR-Cpf1 endonucleases could provide an alternative to CRISPR-Cas9 endonucleases, but the determinants of targeting specificity are not well understood. Using mismatched crRNAs we found that Cpf1 could tolerate single or double mismatches in the 3' PAM-distal region, but not in the 5' PAM-proximal region. Genome-wide analysis of cleavage sites in vitro for eight Cpf1 nucleases using Digenome-seq revealed that there were 6 (LbCpf1) and 12 (AsCpf1) cleavage sites per crRNA in the human genome, fewer than are present for Cas9 nucleases (>90). Most Cpf1 off-target cleavage sites did not produce mutations in cells. We found mismatches in either the 3' PAM-distal region or in the PAM sequence of 12 off-target sites that were validated in vivo. Off-target effects were completely abrogated by using preassembled, recombinant Cpf1 ribonucleoproteins. PMID- 27272385 TI - Targeted mutagenesis in mice by electroporation of Cpf1 ribonucleoproteins. PMID- 27272387 TI - Generation of knockout mice by Cpf1-mediated gene targeting. PMID- 27272388 TI - Coping, adapting or self-managing - what is the difference? A concept review based on the neurological literature. AB - AIM: The aim of this study was to report: (1) an analysis of the concepts of coping, adaptation and self-management in the context of managing a neurological condition; and (2) the overlap between the concepts. BACKGROUND: The three concepts are often confused or used interchangeably. Understanding similarities and differences between concepts will avoid misunderstandings in care. The varied and often unpredictable symptoms and degenerative nature of neurological conditions make this an ideal population in which to examine the concepts. DESIGN: Concept analysis. DATA SOURCES: Articles were extracted from a large literature review about living with a neurological condition. The original searches were conducted using SCOPUS, EMBASE, CINAHL and Psych INFO. Seventy seven articles met the inclusion criteria of: (1) original article concerning coping, adaptation or self-management of a neurological condition; (2) written in English; and (3) published between 1999-2011. METHODS: The concepts were examined according to Morse's concept analysis method; structural elements were then compared. RESULTS: Coping and adaptation to a neurological condition showed statistically significant overlap with a common focus on internal management. In contrast, self-management appears to focus on disease-controlling and health related management strategies. Coping appears to be the most mature concept, whereas self-management is least coherent in definition and application. CONCLUSION: All three concepts are relevant for people with neurological conditions. Healthcare teams need to be cautious when using these terms to avoid miscommunication and to ensure clients have access to all needed interventions. Viewing the three concepts as a complex whole may be more aligned with client experience. PMID- 27272389 TI - Application of image cytometry to characterize heterologous lipid flippases in yeast. AB - Lipid flippases are integral membrane proteins that play a central role in moving lipids across cellular membranes. Some of these transporters are ATPases that couple lipid translocation to ATP hydrolysis, whereas others function without any discernible metabolic energy input. A growing number of lipid flippases has been identified but key features of their activity remain to be elucidated. A well established method to characterize ATP-driven flippases is based on their heterologous expression in yeast, followed by incubation of the cells with fluorescent lipids. Internalization of these probes is typically monitored by flow cytometry, a costly and maintenance-intensive method. Here, we have optimized a protocol to use an automated image-based cell counter to accurately measure lipid uptake by heterologous lipid flippases expressed in yeast. The method was validated by comparison with the classical flow cytometric evaluation of lipid-labeled cells. In addition, we demonstrated that expression of fluorescently tagged flippase complexes can be directly co-related with fluorescent lipid uptake using the image-based cell counter system. The method extends the number of techniques available for characterization of lipid flippase activity, and should be readily adaptable to analyze a variety of other transport systems in yeast, parasites, and mammalian cells. (c) 2016 International Society for Advancement of Cytometry. PMID- 27272386 TI - Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. AB - Hematopoietic stem cell transplantation (HSCT) offers curative therapy for patients with hemoglobinopathies, congenital immunodeficiencies, and other conditions, possibly including AIDS. Autologous HSCT using genetically corrected cells would avoid the risk of graft-versus-host disease (GVHD), but the genotoxicity of conditioning remains a substantial barrier to the development of this approach. Here we report an internalizing immunotoxin targeting the hematopoietic-cell-restricted CD45 receptor that effectively conditions immunocompetent mice. A single dose of the immunotoxin, CD45-saporin (SAP), enabled efficient (>90%) engraftment of donor cells and full correction of a sickle-cell anemia model. In contrast to irradiation, CD45-SAP completely avoided neutropenia and anemia, spared bone marrow and thymic niches, enabling rapid recovery of T and B cells, preserved anti-fungal immunity, and had minimal overall toxicity. This non-genotoxic conditioning method may provide an attractive alternative to current conditioning regimens for HSCT in the treatment of non-malignant blood diseases. PMID- 27272390 TI - Enantioselective Palladium-Catalyzed Oxidative beta,beta-Fluoroarylation of alpha,beta-Unsaturated Carbonyl Derivatives. AB - The site-selective palladium-catalyzed three-component coupling of deactivated alkenes, arylboronic acids, and N-fluorobenzenesulfonimide is disclosed herein. The developed methodology establishes a general, modular, and step-economical approach to the stereoselective beta-fluorination of alpha,beta-unsaturated systems. PMID- 27272391 TI - Evaluation of the effect of transcytolemmal water exchange analysis for therapeutic response assessment using DCE-MRI: a comparison study. AB - This study compares the shutter-speed (SS) and the Tofts models as used in assessing therapeutic response in a longitudinal DCE-MRI experiment. Sixteen nu/nu mice with implanted colorectal adenocarcinoma cell line (LS-174T) were randomly assigned into treatment/control groups (n = 8/group) and received bevacizumab/saline twice weekly (Day1/Day4/Day8). All mice were scanned at one pre- (Day0) and two post-treatment (Day2/Day9) time points using a high spatiotemporal resolution DCE-MRI pulse sequence. The CA extravasation rate constant [Formula: see text] from the Tofts/SS model and the mean intracellular water residence time [Formula: see text] from the SS model were analyzed. A biological subvolume (BV) within the tumor was identified based on the [Formula: see text] intensity distribution, and the SS model parameters within the BV ([Formula: see text] and [Formula: see text]) were analyzed. It is found that [Formula: see text] and [Formula: see text] have a similar spatial distribution in the tumor volume. The Bayesian information criterion results show that the SS model was a better fit for all scans. At Day9, the treatment group had significantly higher tumor mean [Formula: see text] (p = 0.021), [Formula: see text] (p = 0.021) and [Formula: see text] (p = 0.045). When BV from transcytolemmal water exchange analysis was adopted, the treatment group had higher mean [Formula: see text] at both Day2 (p = 0.038) and Day9 (p = 0.007). Additionally, at Day9, the treatment group had higher mean [Formula: see text] (p = 0.045) and higher [Formula: see text] spatial heterogeneity indices (Renyi dimensions) d 1 (p = 0.010) and d 2 (p = 0.021). When mean [Formula: see text] and its coefficient of variation (CV) were used to separate treatment/control group samples using supporting vector machine, the accuracy of treatment/control classification was 68.8% at Day2 and 87.5% at Day9; in contrast, the Day2/Day9 accuracy were 62.5%/87.5% using tumor mean [Formula: see text] and its CV and were 50.0%/87.5% using tumor mean [Formula: see text] and its CV, respectively. These results suggest that the SS model parameters outperformed the Tofts model parameters in terms of capturing bevacizumab therapeutic effect in this longitudinal experiment. PMID- 27272393 TI - Attachment and proliferation of dental pulp stem cells on dentine treated with different regenerative endodontic protocols. AB - AIM: To investigate the attachment and proliferation of dental pulp stem cells (DPSC) on dentine treated with various endodontic regeneration protocols. METHODOLOGY: Standardized dentine samples were irrigated with sodium hypochlorite (1.5% NaOCl) and ethylenediaminetetraacetic acid (17% EDTA) and randomized into four treatment groups and two control groups. The treatment groups were treated with a clinically used concentration of triple antibiotic paste (TAP), double antibiotic paste (DAP), calcium hydroxide (Ca(OH)2 ) or diluted TAP in a methylcellulose system (DTAP) for 1 week. Each sample in the treatment groups was then irrigated with EDTA. The two control groups were treated with EDTA or received no treatment. Dental pulp stem cells were seeded on each dentine specimen (10 000 cells). Lactate dehydrogenase activity assays were then performed to evaluate the attached DPSC after 1 day of incubation. Water-soluble tetrazolium assays were used to determine DPSC proliferation after three additional days of incubation. Friedman's test followed by least significant difference were used for statistical analyses (alpha = 0.05). RESULTS: Triple antibiotic paste and DTAP regeneration protocols, as well as EDTA-treated dentine, caused significant increases in DPSC attachment to dentine. Triple antibiotic paste, DAP and Ca(OH)2 regeneration protocols caused significant reductions in DPSC proliferation on dentine. However, the DTAP regeneration protocol did not have any significant negative effects on DPSC proliferation. CONCLUSIONS: The clinically used endodontic regeneration protocols that include the use of TAP, DAP or Ca(OH)2 medicament negatively affected DPSC proliferation on dentine. However, the use of DTAP medicament during regenerative endodontic treatment may not adversely affect the proliferation of DPSC. PMID- 27272392 TI - Polymorphisms of CHAT but not TFAM or VR22 are Associated with Alzheimer Disease Risk. AB - BACKGROUND Alzheimer disease (AD) is a chronic neurodegenerative disease that is one of the most prevalent health problems among seniors. The cause of AD has not yet been elucidated, but many risk factors have been identified that might contribute to the pathogenesis and prognosis of AD. We conducted a meta-analysis of studies involving CHAT, TFAM, and VR22 polymorphisms and AD susceptibility to further understand the pathogenesis of AD. MATERIAL AND METHODS PubMed/Medline, Embase, Web of Science, the Cochrane Library, and Google Scholar were searched for relevant articles. Rs1880676, rs2177369, rs3810950, and rs868750 of CHAT; rs1937 and rs2306604 of TFAM; and rs10997691 and rs7070570 of VR22 are studied in this meta-analysis. RESULTS A total of 51 case-control studies with 16 446 cases and 16 057 controls were enrolled. For CHAT, rs2177369 (G>A) in whites and rs3810950 (G>A) in Asians were found to be associated with AD susceptibility. No association was detected between rs1880676 and rs868750 and AD risk. For TFAM and VR22, no significant association was detected in studied single-nucleotide polymorphisms (SNPs). CONCLUSIONS Rs2177369 and rs3810950 of CHAT are associated with AD susceptibility, but rs1880676 and rs868750 are not. Rs1937 and rs2306604 of TFAM, and rs10997691 and rs7070570 of VR22 are not significantly associated with AD risk. PMID- 27272394 TI - Optical modulation of nano-gap tunnelling junctions comprising self-assembled monolayers of hemicyanine dyes. AB - Light-driven conductance switching in molecular tunnelling junctions that relies on photoisomerization is constrained by the limitations of kinetic traps and either by the sterics of rearranging atoms in a densely packed monolayer or the small absorbance of individual molecules. Here we demonstrate light-driven conductance gating; devices comprising monolayers of hemicyanine dyes trapped between two metallic nanowires exhibit higher conductance under irradiation than in the dark. The modulation of the tunnelling current occurs faster than the timescale of the measurement (~1 min). We propose a mechanism in which a fraction of molecules enters an excited state that brings the conjugated portion of the monolayer into resonance with the electrodes. This mechanism is supported by calculations showing the delocalization of molecular orbitals near the Fermi energy in the excited and cationic states, but not the ground state and a reasonable change in conductance with respect to the effective barrier width. PMID- 27272396 TI - Editorial for Planta Medica Special Issue Marine Natural Products. PMID- 27272395 TI - Network representation of protein interactions-Experimental results. AB - A graph theoretical analysis of nuclear magnetic resonance (NMR) data of six different protein interactions has been presented. The representation of the protein interaction data as a graph or network reveals that all of the studied interactions are based on a common functional concept. They all involve a single densely packed hub of functionally correlated residues that mediate the ligand binding events. This is found independent of the kind of protein (folded or unfolded) or ligand (protein, polymer or small molecule). Furthermore, the power of the graph analysis is demonstrated at the examples of the Calmodulin (CaM)/Calcium and the Cold Shock Protein A (CspA)/RNA interaction. The presented approach enables the precise determination of multiple binding sites for the respective ligand molecules. PMID- 27272397 TI - A Hexa-Herbal TCM Decoction Used to Treat Skin Inflammation: An LC-MS-Based Phytochemical Analysis. AB - In order to understand the chemical relationship between a traditional hexa herbal Chinese medicine formula and botanical drugs it is derived from, an analytical platform comprising liquid chromatography coupled with triple quadrupole mass spectrometry and data mining was developed to separate and identify key chemical components. The hexa-herbal formula comprises the rootstock of Scutellaria baicalensis, Rheum tanguticum, Sophora flavescens, the root bark of Dictamnus dasycarpus, the bark of Phellodendron chinense, and the fruit of Kochia scoparia. Seventy-three compounds including alkaloids, anthraquinone derivatives, coumarins, coumarins derivatives, flavonoids, flavone glycosides, naphthalene derivatives, phenylbutanone glucopyranoside, phenolic acids, pterocarpans, stilbenes, stilbenes derivatives, and tannins were putatively identified based on mass measurement and characteristic fragment ions. Among the botanical drugs of the hexa-herbal Chinese medicine formula, the rootstock of R. tanguticum and S. flavescens, bark of P. chinense, and rootstock of S. baicalensis contributed to the majority of the extracted metabolites of the formula decoction. The developed method appeared to be a versatile tool for monitoring chemical constituents in extracts of a traditional Chinese medicine formula in a relatively comprehensive and systematic manner, and helped to understand the importance of the individual botanical drugs within a formulation. PMID- 27272398 TI - Herpecaudin from Herpetospermum caudigerum, a Xanthine Oxidase Inhibitor with a Novel Isoprenoid Scaffold. AB - Herpecaudin (3), a xanthine oxidase inhibitor with an unprecedented scaffold, was discovered from Herpetospermum caudigerum seeds. The structure was determined by spectroscopic and X-ray single crystallographic methods. A possible biogenetic pathway leading to herpecaudin is proposed, starting from congeners 23,24 dihydrocucurbitacin E (1) and endecaphyllacin B (2), and involving retro-aldol cleavage as a key step. All three compounds proved to be active and represent new scaffolds of non-purine analogue xanthine oxidase inhibitors. PMID- 27272399 TI - Polyoxypregnane Glycosides from the Roots of Marsdenia tenacissima and Their Anti HIV Activities. AB - A continuous phytochemical study on the roots of Marsdenia tenacissima led to the isolation and identification of 13 new polyoxypregnane glycosides named marstenacissides B10-B17 (1, 2, 4, 7, 8, 11, 12, and 14) and marstenacissides A8 A12 (3, 9, 10, 13, and 15) in addition to two known polyoxypregnane glycosides marsdenosides M and L (5 and 6). Their structures were established by spectroscopic techniques and by comparison with the reported data in the literature. Moreover, the anti-HIV activities of these isolates and the previous isolated marstenacissides A1-A7 and B1-B9 were assessed, some of which exhibited slight or negligible effects against HIV-1. PMID- 27272400 TI - MicroRNAs as New Bioactive Components in Medicinal Plants. AB - Herbal medicine has been used to treat diseases for centuries; however, the biological active components and the mechanistic understanding of actions of plant-derived drugs are permanently discussed. MicroRNAs are a class of small, non-coding RNAs that play crucial roles as regulators of gene expression. In recent years, an increasing number of reports showed that microRNAs not only execute biological functions within their original system, they can also be transmited from one species to another, inducing a posttranscriptional repression of protein synthesis in the recipient. This cross-kingdom regulation of microRNAs provides thrilling clues that small RNAs from medicinal plants might act as new bioactive components, interacting with the mammalian system.In this article, we provide an overview of the cross-kingdom communication of plant-derived microRNAs. We summarize the microRNAs identified in medicinal plants, their potential targets in mammals, and discuss several recent studies concerning the therapeutic applications of plant-based microRNAs. Health regulations of herbal microRNAs in mammals are a new concept. Continuing efforts in this area will broaden our understanding of biological actions of herbal remedies, and will open the way for the development of new approaches to prevent or treat human diseases. PMID- 27272401 TI - Graph states of prime-power dimension from generalized CNOT quantum circuit. AB - We construct multipartite graph states whose dimension is the power of a prime number. This is realized by the finite field, as well as the generalized controlled-NOT quantum circuit acting on two qudits. We propose the standard form of graph states up to local unitary transformations and particle permutations. The form greatly simplifies the classification of graph states as we illustrate up to five qudits. We also show that some graph states are multipartite maximally entangled states in the sense that any bipartition of the system produces a bipartite maximally entangled state. We further prove that 4-partite maximally entangled states exist when the dimension is an odd number at least three or a multiple of four. PMID- 27272402 TI - Drosophila wing modularity revisited through a quantitative genetic approach. AB - To predict the response of complex morphological structures to selection it is necessary to know how the covariation among its different parts is organized. Two key features of covariation are modularity and integration. The Drosophila wing is currently considered a fully integrated structure. Here, we study the patterns of integration of the Drosophila wing and test the hypothesis of the wing being divided into two modules along the proximo-distal axis, as suggested by developmental, biomechanical, and evolutionary evidence. To achieve these goals we perform a multilevel analysis of covariation combining the techniques of geometric morphometrics and quantitative genetics. Our results indicate that the Drosophila wing is indeed organized into two main modules, the wing base and the wing blade. The patterns of integration and modularity were highly concordant at the phenotypic, genetic, environmental, and developmental levels. Besides, we found that modularity at the developmental level was considerably higher than modularity at other levels, suggesting that in the Drosophila wing direct developmental interactions are major contributors to total phenotypic shape variation. We propose that the precise time at which covariance-generating developmental processes occur and/or the magnitude of variation that they produce favor proximo-distal, rather than anterior-posterior, modularity in the Drosophila wing. PMID- 27272403 TI - Matrix-assisted diffusion-ordered spectroscopy: choosing a matrix. AB - Diffusion-ordered spectroscopy (DOSY) is an important technique for separating the NMR signals of the components in a mixture, and relies on differences in diffusion coefficient. Standard DOSY experiments therefore struggle when the components of a mixture are of similar size, and hence diffuse at similar rates. Fortunately, the diffusion coefficients of solutes can be manipulated by changing the matrix in which they diffuse, using matrix components that interact differentially with them, a technique known as matrix-assisted DOSY. In the present investigation, we evaluate the performance of a number of new, previously used, and mixed matrices with an informative test mixture: the three positional isomers of dihydroxybenzene. The aim of this work is to present the matrix assisted DOSY user with information about the potential utility of a set of matrices (and combinations of matrices), including ionic and non-ionic surfactants, complexing agents, polymers, and mixed solvents. A variety of matrices improved the diffusion resolution of the signals of the test system, with the best separation achieved by mixed micelles of sodium dodecyl sulfate and cetyl trimethylammonium bromide. The use of mixed matrices offers great potential for the analyst to tailor the matrix to a particular sample under study. (c) 2016 The Authors Magnetic Resonance in Chemistry Published by John Wiley & Sons, Ltd. PMID- 27272404 TI - Evaluating patient safety indicators in orthopedic surgery between Italy and the USA. AB - OBJECTIVE: To compare patient safety in major orthopedic procedures between an orthopedic hospital in Italy, and 26 US hospitals of similar size. DESIGN: Retrospective analysis of administrative data from hospital discharge records in Italy and Florida, USA, 2011-13. Patient Safety Indicators (PSIs) developed by the Agency for Healthcare Quality and Research were used to identify inpatient adverse events (AEs). We examined the factors associated with the development of each different PSI, taking into account known confounders, using logistic regression. SETTING: One Italian orthopedic hospital and 26 hospitals in Florida with >= 1000 major orthopedic procedures per year. PARTICIPANTS: Patients >= 18 years who underwent 1 of the 17 major orthopedic procedures, and with a length of stay (LOS) > 1 day. INTERVENTION: Patient Safety management between Italy and the USA. MAIN OUTCOME MEASURE: Patient Safety Indicators. RESULTS: A total of 14 393 patients in Italy (mean age = 59.8 years) and 131 371 in the USA (mean age = 65.4 years) were included. US patients had lower adjusted odds of developing a PSI compared to Italy for pressure ulcers (odds ratio [OR]: 0.21; 95% confidence interval [CI]: 0.10-0.45), hemorrhage or hematoma (OR: 0.42; CI 0.23-0.78), physiologic and metabolic derangement (OR: 0.08; CI 0.02-0.37). Italian patients had lower odds of pulmonary embolism/deep vein thrombosis (OR: 3.17; CI 2.16 4.67) compared to US patients. CONCLUSIONS: Important differences in patient safety events were identified across countries using US developed PSIs. Though caution about potential coding differences is wise when comparing PSIs internationally, other differences may explain AEs, and offer opportunities for cross-country learning about safe practices. PMID- 27272405 TI - Strategies facilitating practice change in pediatric cancer: a systematic review. AB - PURPOSE: By conducting a systematic review, we describe strategies to actively disseminate knowledge or facilitate practice change among healthcare providers caring for children with cancer and we evaluate the effectiveness of these strategies. DATA SOURCES: We searched Ovid Medline, EMBASE and PsychINFO. STUDY SELECTION: Fully published primary studies were included if they evaluated one or more professional intervention strategies to actively disseminate knowledge or facilitate practice change in pediatric cancer or hematopoietic stem cell transplantation. DATA EXTRACTION: Data extracted included study characteristics and strategies evaluated. In studies with a quantitative analysis of patient outcomes, the relationship between study-level characteristics and statistically significant primary analyses was evaluated. RESULTS OF DATA SYNTHESIS: Of 20 644 titles and abstracts screened, 146 studies were retrieved in full and 60 were included. In 20 studies, quantitative evaluation of patient outcomes was examined and a primary outcome was stated. Eighteen studies were 'before and after' design; there were no randomized studies. All studies were at risk for bias. Interrupted time series was never the primary analytic approach. No specific strategy type was successful at improving patient outcomes. CONCLUSIONS: Literature describing strategies to facilitate practice change in pediatric cancer is emerging. However, major methodological limitations exist. Studies with robust designs are required to identify effective strategies to effect practice change. PMID- 27272406 TI - Impact of continuity of care on preventable hospitalization of patients with type 2 diabetes: a nationwide Korean cohort study, 2002-10. AB - OBJECTIVE: To determine whether patients with greater continuity of care (COC) have fewer preventable hospitalizations. DESIGN: We conducted a cohort study using a stratified random sample of Korean National Health Insurance enrollees from 2002 to 2010. The COC index was calculated for each year post-diagnosis based on ambulatory care visits. We performed a recurrent event survival analysis via Cox proportional hazard regression analysis of preventable hospitalizations. STUDY PARTICIPANTS: A total of 5163 patients newly diagnosed with type 2 diabetes mellitus in 2003-6 and receiving oral hypoglycemic medication. MAIN OUTCOME MEASURE: Preventable hospitalization. RESULTS: Of 5163 eligible participants, 6.4% (n = 328) experienced a preventable hospitalization during the study period. The adjusted hazard ratio (HR) was 8.69 (95% CI, 2.62-28.83) for subjects with a COC score of 0.00-0.19, 7.03 (95% CI, 4.50-10.96) for those with a score of 0.20 0.39, 3.01 (95% CI, 2.06-4.40) for those with a score of 0.40-059, 4.42 (95% CI, 3.04-6.42) for those with a score of 0.60-0.79 and 5.82 (95% CI, 3.87-8.75) for those with a score of 0.80-0.99. The difference in cumulative incidence of preventable hospitalizations in patients with COC scores of 0.00-0.19 relative to those with COC scores of 1.00 was the greatest, at 0.97% points. CONCLUSIONS: Greater COC was associated with fewer preventable hospitalizations in subjects with type 2 diabetes. PMID- 27272408 TI - Whole exome sequencing identifies multiple diagnoses in congenital glaucoma with systemic anomalies. AB - The genetic basis of congenital glaucoma with systemic anomalies is largely unknown. Whole exome sequencing (WES) in 10 probands with congenital glaucoma and variable systemic anomalies identified pathogenic or likely pathogenic variants in three probands; in two of these, a combination of two Mendelian disorders was found to completely explain the patients' features whereas in the third case only the ocular findings could be explained by the genetic diagnosis. The molecular diagnosis for glaucoma included two cases with compound heterozygous or homozygous pathogenic alleles in CYP1B1 and one family with a dominant pathogenic variant in FOXC1; the second genetic diagnosis for the additional systemic features included compound heterozygous mutations in NPHS1 in one family and a heterozygous 18q23 deletion in another pedigree. These findings show the power of WES in the analysis of complex conditions and emphasize the importance of CYP1B1 screening in patients with congenital glaucoma regardless of the presence/absence of other systemic anomalies. PMID- 27272407 TI - Patterns of taxonomic, phylogenetic diversity during a long-term succession of forest on the Loess Plateau, China: insights into assembly process. AB - Quantifying the drivers underlying the distribution of biodiversity during succession is a critical issue in ecology and conservation, and also can provide insights into the mechanisms of community assembly. Ninety plots were established in the Loess Plateau region of northern Shaanxi in China. The taxonomic and phylogenetic (alpha and beta) diversity were quantified within six succession stages. Null models were used to test whether phylogenetic distance observed differed from random expectations. Taxonomic beta diversity did not show a regular pattern, while phylogenetic beta diversity decreased throughout succession. The shrub stage occurred as a transition from phylogenetic overdispersion to clustering either for NRI (Net Relatedness Index) or betaNRI. The betaNTI (Nearest Taxon Index) values for early stages were on average phylogenetically random, but for the betaNRI analyses, these stages were phylogenetically overdispersed. Assembly of woody plants differed from that of herbaceous plants during late community succession. We suggest that deterministic and stochastic processes respectively play a role in different aspects of community phylogenetic structure for early succession stage, and that community composition of late succession stage is governed by a deterministic process. In conclusion, the long-lasting evolutionary imprints on the present-day composition of communities arrayed along the succession gradient. PMID- 27272410 TI - Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer. AB - Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response to CRT would be valuable for individualizing treatment for LARC patients. The current study used metabolomics-based approaches to identify molecular markers that predict the response to CRT. Seventy-six patients with LARC who received pelvic radiotherapy and concurrent chemotherapy using tegafur-uracil and leucovorin were enrolled. Radical surgery was performed 6-8 weeks after the completion of CRT. The postsurgical pathological CRT response was evaluated using the ypStage or tumor regression grade. Profiling patterns of low-mass ions (LMIs) in the pretreatment sera were obtained from all patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Our previously developed two-step algorithms, which showed a powerful diagnostic capability during colorectal cancer screening, were then used to screen for meaningful LMIs with discriminatory power. One combination consisting of seven LMIs was identified, whose discriminatory score separated a good CRT response (ypStage 0 1) from a poor CRT response (ypStage 3-4) successfully. However, each individual LMI alone showed insignificant discriminatory power. This finding suggests that analysis of the LMIs in pretreatment serum could serve as a predictive marker of the CRT response in patients with LARC. PMID- 27272411 TI - Heterogeneous expression of A33 in colorectal cancer: possible explanation for A33 antibody treatment failure. AB - The A33 protein, expressed in colorectal tumors, is a target for improving treatment of patients with colorectal cancer. Over the last decade, studies have tested anti-A33 antibody as a therapeutic agent for these patients. Preclinical results were promising, but clinical trials did not confirm positive results. Here, immunohistochemistry in colorectal cancer tissue showed that samples from well-differentiated tumors presented a strong A33 membrane staining, whereas poorly differentiated tumors and mucinous adenocarcinomas showed weak cytoplasmic and nuclear staining. Moderately differentiated tumors presented variable staining. We suggest that in future clinical trials, patients should be selected on the basis of membrane expression of A33. PMID- 27272409 TI - Glucose induced activation of canonical Wnt signaling pathway in hepatocellular carcinoma is regulated by DKK4. AB - Elevated glycemic index, an important feature of diabetes is implicated in an increased risk of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of this association are relatively less explored. Present study investigates the effect of hyperglycemia over HCC proliferation. We observed that high glucose culture condition (HG) specifically activates canonical Wnt signaling in HCC cells, which is mediated by suppression of DKK4 (a Wnt antagonist) expression and enhanced beta-catenin level. Functional assays demonstrated that a normoglycemic culture condition (NG) maintains constitutive expression of DKK4, which controls HCC proliferation rate by suppressing canonical Wnt signaling pathway. HG diminishes DKK4 expression leading to loss of check at G0/G1/S phases of the cell cycle thereby enhancing HCC proliferation, in a beta-catenin dependent manner. Interestingly, in NOD/SCID mice supplemented with high glucose, HepG2 xenografted tumors grew rapidly in which elevated levels of beta-catenin, c-Myc and decreased levels of DKK4 were detected. Knockdown of DKK4 by shRNA promotes proliferation of HCC cells in NG, which is suppressed by treating cells exogenously with recombinant DKK4 protein. Our in vitro and in vivo results indicate an important functional role of DKK4 in glucose facilitated HCC proliferation. PMID- 27272412 TI - Epidermal growth factor receptor inhibition in metastatic anal cancer. AB - Metastatic squamous cell carcinoma (SCCA) anal cancer is relatively rare. With limited data, cisplatin plus 5-fluorouracil has traditionally been utilized in the first-line setting. Treatment beyond front-line cisplatin progression is not well defined. Epidermal growth factor receptor (EGFR) is highly overexpressed in SCCA anal cancer and EGFR inhibition may represent a potential treatment target for this population in need. Our case series evaluated metastatic SCCA anal cancer patients who received an EGFR monoclonal antibody as second-line or third line therapy. Data collected consisted of demographics, previous treatment, metastatic disease sites, localized therapy received, regimen received, first radiographic result, progression-free survival, and overall survival. A total of 17 patients were included, with most (76%) patients receiving an EGFR monoclonal antibody in the second-line setting. Common regimens identified combined cetuximab or panitumumab with a fluoropyrimidine plus platinum (35%), carboplatin plus paclitaxel (29%), or cisplatin plus vinorelbine (18%). Thirty-five percent of patients achieved a response and 24% had stable disease. The overall median progression-free survival and overall survival were 7.3 and 24.7 months, respectively. Compared with our large retrospective study in the front-line metastatic anal cancer setting, our study suggests that anti-EGFR therapy in combination with certain chemotherapy derived additional benefit in the refractory setting. In the metastatic setting, there is a need to discover effective therapies. We present a diverse metastatic SCCA anal cancer patient population who received cetuximab or panitumumab with chemotherapy in the second line or third-line setting. Our case series strengthens the concept of EGFR inhibition in metastatic SCCA anal cancer. PMID- 27272413 TI - Retrospective analysis of cardiovascular diseases related to chemotherapies for advanced solid tumor patients. AB - Appropriate management of cardiovascular diseases (CVDs) related to chemotherapy for solid tumors is important for safe oncologic treatment. However, prediction of the onset and progression of CVDs has not generally been established in Japan. We carried out a retrospective analysis of advanced or recurrent solid tumor patients who received chemotherapies in a single institution. Patient characteristics, chemotherapy regimens, adverse events, CVDs before chemotherapy, and diagnosis of CVDs in association with chemotherapy were assessed. During the period from April 2006 to March 2012, 394 patients were examined. Cardiac diseases (CDs), hypertension (HT), or arterial thrombosis or venous thromboembolism were prevalent in 37 (9.4%), 22 (5.6%), five (1.3%), and 14 (3.5%) cases, respectively. HT (14.5%) and venous thrombosis (5.8%) were frequent in patients who received bevacizumab-containing chemotherapy. Four cases with left ventricular dysfunction experienced a decrease of ejection fraction and early filling/atrial filling (E/A) and E/A tended to decrease before ejection fraction. Ninety (62.1%) of 145 cases showed an increase in the D-dimer (DD) level before chemotherapy, and a further increase in DD level was found when venous thrombosis occurred. Relative risks of the disease progression of HT, CD, and thromboembolism because of chemotherapy were 1.3, 1.9, and 3.6, respectively. A decrease in E/A and an increase in DD were suggested to be valuable for early diagnosis of the respective onsets of left ventricular dysfunction and venous thrombosis related to chemotherapy. We conclude that patients with previous CD tend to have disease progression of CD during chemotherapy. PMID- 27272415 TI - Copper(II)-Catalyzed Nitroaldol (Henry) Reactions: Recent Developments. AB - Self-assembled copper(II) complexes are described as effective catalysts for nitroaldol (Henry) reactions on water. The protocol involves a heterogeneous process and the catalysts can be recovered and recycled without loss of activity. Further, C2-symmetric N,N'-substituted chiral copper(II) salan complexes are found to be more effective catalysts than chiral copper(II) salen complexes for reactions in homogeneous catalysis, with high enantioselectivities. The reactions involve bifunctional catalysis, bearing the properties of a Bronsted base, as well as a Lewis acid, to effect the reaction in the absence of external additives. PMID- 27272416 TI - Historical and Contemporary Patterns of Mercury in a Hydroelectric Reservoir and Downstream Fishery: Concentration Decline in Water and Fishes. AB - Mercury (Hg) contamination can pose risks to human and animal health as well as commercial fisheries. Reservoir construction in riverine systems produces flooded conditions amenable to Hg(II)-methylating bacteria, which can transform this relatively benign environmental contaminant into the bioaccumulative, environmentally relevant, and neurotoxic methyl-Hg (MeHg). Hg concentrations ([Hg]) in fishes from reservoirs can take decades to decrease to pre-dam levels, but less is known about Hg exported downstream and its dynamics within downstream fish populations. We examined and compared the multidecadal rates of biotic [Hg] decrease and contemporary factors affecting [Hg] in fish collected from a hydroelectric reservoir (Tobin Lake) and a related downstream fishery (Cumberland Lake) along the Saskatchewan River, Canada. Rates of [Hg] decrease were considered in four species-northern pike (Esox lucius), sauger (Sander canadensis), goldeye (Hiodon alosoides), and walleye (S. vitreus)-all of which showed a significant decrease over time (p < 0.001) and are now lower than Health Canada consumption guidelines (0.5 MUg/g). Rates of decrease ranged from 0.5 to 3.9 %/year and were similar between sites in the cases of northern pike and sauger. Contemporary factors affecting [Hg] in walleye collected downstream include fish length (p < 0.001), fish age (p < 0.001), and trophic magnification through the food web (p < 0.001), and relationships between [Hg] and trophic level in predatory and prey fish are now similar to those found in non-Hg inundated systems at a similar latitude. Together, these results suggest connected contamination between the two sites and delineate the timeline during which [Hg] in a variety of fish species decreased to nontoxic levels in both locations. PMID- 27272414 TI - Genome-Wide Association Study of Acute Renal Graft Rejection. AB - Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant single nucleotide polymorphisms (SNPs) from the discovery cohort. In the discovery cohort, we found five candidate loci tagged by a number of contiguous SNPs (more than five) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor type tyrosine kinase essential for B cell receptor signaling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium. PMID- 27272417 TI - Looking for Trouble. PMID- 27272418 TI - Big Data Research Requires a Big Role for Primary Care. PMID- 27272419 TI - Poor Performance Among Trainees in a Dutch Postgraduate GP Training Program. AB - BACKGROUND AND OBJECTIVES: Poor performance among trainees is an important issue, for patient safety and economic reasons. While early identification might enhance remediation measures, we explored the frequency, nature, and risk factors of poor performance in a Dutch postgraduate general practitioner (GP) training program. METHODS: All trainees who started the GP training between 2005 and 2007 were included. Multivariate logistic regression analysis was applied to examine associations between individual characteristics; early assessments of competencies and knowledge, training process characteristics (eg, illness, maternal leave), and the outcome poor performance; sub-analyses were performed for each year. RESULTS: A total of 215 trainees started the 3-year GP program, and 49 (22.8%) exhibited poor performance (in one or more years). In the first and second years, problem areas among poor performers were equally distributed across the roles of "medical expert," "communicator," and "professional." In the third year, shortcomings in "professionalism" were the most common problem. Increasing age was a risk factor for poor performance as were insufficient scores in communication and knowledge. Poor performance in the previous year was a risk factor for poor performance in the second and third years; OR=4.20 (CI=1.31- 13.47) and OR=5.40 (CI=1.58--18.47), respectively. CONCLUSIONS: Poor performance is prevalent but primarily occurring within a single training year. This finding suggests that trainees are capable of solving trainee problems. Increasing age, insufficient assessment scores early in the training, and poor performance in a previous year constitute risk factors for poor performance. PMID- 27272420 TI - CERA: Clerkships Need National Curricula on Care Delivery, Awareness of Their NCC Gaps. AB - BACKGROUND AND OBJECTIVES: The Society of Teachers of Family Medicine's (STFM) National Clerkship Curriculum (NCC) was created to standardize and improve teaching of a minimum core curriculum in family medicine clerkships, promoting the Triple Aim of better care and population health at lower cost. It includes competencies all clerkships should teach and tools to support clerkship directors (CDs). This 2014 CERA survey of clerkship directors is one of several needs assessments that guide STFM's NCC Editorial Board in targeting improvements and peer-review processes. METHODS: CERA's 2014 survey of CDs was sent to all 137 CDs at US and Canadian allopathic medical schools. Primary aims included: (1) Identify curricular topics of greatest need, (2) Inventory the percent of family medicine clerkships teaching each NCC topic, and (3) Determine if longitudinal or blended clerkship have unique needs. This survey also assessed use of NCC to advocate for teaching resources and collaborate with colleagues at other institutions. RESULTS: Ninety-one percent of CDs completed the survey. Sixty-four percent reported their clerkship covers all of the NCC minimum core, but on detailed analysis, only 1% teach all topics. CDs need curricula on care delivery topics (cost-effective approach to acute care, role of family medicine in the health care system, quality/safety, and comorbid substance abuse). CONCLUSIONS: Single-question assessments overestimate the percentage of clerkships teaching all of the NCC minimum core. Clerkships need national curricula on care delivery topics and tools to help them find their curricular gaps. PMID- 27272421 TI - The State of Communication Education in Family Medicine Residencies. AB - BACKGROUND AND OBJECTIVES: Communication skills are essential to medical training and have lasting effects on patient satisfaction and adherence rates. However, relatively little is reported in the literature identifying how communication is taught in the context of residency education. Our goal was to determine current practices in communication curricula across family medicine residency programs. METHODS: Behavioral scientists and program directors in US family medicine residencies were surveyed via email and professional organization listservs. Questions included whether programs use a standardized communication model, methods used for teaching communication, hours devoted to teaching communication, as well as strengths and areas for improvement in their program. Analysis identified response frequencies and ranges complemented by analysis of narrative comments. RESULTS: A total of 204 programs out of 458 family medicine residency training sites responded (45%), with 48 out of 50 US states represented. The majority of respondents were behavioral scientists. Seventy-five percent of programs identified using a standard communication model; Mauksch's patient centered observation model (34%) was most often used. Training programs generally dedicated more time to experiential teaching methods (video review, work with simulated patients, role plays, small groups, and direct observation of patient encounters) than to lectures (62% of time and 24% of time, respectively). The amount of time dedicated to communication education varied across programs (average of 25 hours per year). Respondent comments suggest that time dedicated to communication education and having a formal curriculum in place are most valued by educators. CONCLUSIONS: This study provides a picture of how communication skills teaching is conducted in US family medicine residency programs. These findings can provide a comparative reference and rationale for residency programs seeking to evaluate their current approaches to communication skills teaching and develop new or enhanced curricula. PMID- 27272422 TI - The Impact of Administrative Academic Units (AAU) Grants on the Family Medicine Research Enterprise in the United States. AB - BACKGROUND AND OBJECTIVES: The Health Resources and Services Administration (HRSA) awards funding to primary care departments-or "Academic Administrative Units" (AAUs) at US medical schools-to strengthen or grow these departments and ultimately increase the output of primary care physicians into the US workforce. One aspect of these AAU grants that is often overlooked is the fact that they support research infrastructure for these departments. METHODS: This study used multiple methods, including content analysis of current AAU grant abstracts (n=23), publications resulting from AAU funding (n=79), and survey responses from AAU project directors (n=19) to explore and describe the impact of current AAU grants on family medicine research in the United States. RESULTS: Federal support for family medicine departments remains very low compared to other disciplines. Several AAU grants have provided direct support for research activities as stipulated in the grant abstracts (6/23). However, most grants appear to have facilitated scholarly activity of some sort, including evaluation and quality improvement activities. Two practice-based research networks are supported with AAU funds, and at least 79 publications over the past 10 years, representing a wide variety of methodological approaches and topics, have been produced and indexed in PubMed with explicit acknowledgment of AAU funding. CONCLUSIONS: In the absence of substantial NIH support for family medicine departments, the AAU funding mechanism remains a crucial, but often overlooked, factor in facilitating scholarly activity in departments of family medicine. PMID- 27272423 TI - Family Physician Clinical Compensation in an Academic Environment: Moving Away From the Relative Value Unit. AB - BACKGROUND AND OBJECTIVES: Primary care physician compensation structures have remained largely volume-based, lagging behind changes in reimbursement that increasingly include population approaches such as capitation, bundled payments, and care management fees. We describe a population health-based physician compensation plan developed for two departmental family medicine faculty groups (residency teaching clinic faculty and community clinic faculty) along with outcomes before and after the plan's implementation. METHODS: An observational study was conducted. A pre-post email survey assessed satisfaction with the plan, salary, and salary equity. Physician retention, panel size, and relative value unit (RVU) productivity metrics also were assessed before and after the plan's implementation. RESULTS: Before implementation of the new plan, 18% of residency faculty and 33% of community faculty were satisfied or very satisfied with compensation structure. After implementation, those numbers rose to 47% for residency physicians and 74% for community physicians. Satisfaction with the amount of compensation also rose from 33% to 68% for residency faculty and from 26% to 87% for community faculty. For both groups, panel size per clinical full time equivalent increased, and RVUs moved closer to national benchmarks. RVUs decreased for residency faculty and increased for community faculty. CONCLUSIONS: Aligning a compensation plan with population health delivery by moving rewards away from RVU productivity and toward panel management resulted in improved physician satisfaction and retention, as well as larger panel sizes. RVU changes were less predictable. Physician compensation is an important component of care model redesign that emphasizes population health. PMID- 27272424 TI - Does a Vacation Break Impact the Outcomes of Required Clinical Clerkships? AB - BACKGROUND AND OBJECTIVES: Our objective was to assess the impact of disruption by a new 2-week vacation break on outcomes of required third-year clerkships. METHODS: Mean scores on National Board of Medical Examiners (NBME) clerkship specific clinical science subject ("subject") examinations and overall student evaluations were compared for clerkships with the break and those over the previous 3 years without the break. Students were surveyed about the impact of the break on learning and the time spent studying during the break. RESULTS: No significant differences were found in examination scores between clerkships with the break and those without. Overall student clerkship evaluations were significantly different only for the surgery clerkship. The break was regarded more favorably by students on the 8-week than the 6-week clerkships, but student perspectives varied significantly by specialty. The time reported studying varied significantly by specialty and campus. Student comments were predominantly supportive of the break and focused on the advantages of opportunity to relax, spend time with family, and to study. Concerns included forgetting content knowledge, losing skills, and having difficulty regaining momentum on return to the clerkship. CONCLUSIONS: Interruption of clerkships by a 2-week break was not associated with any significant change in subject examination scores or overall student evaluation of the clerkship, despite predominantly positive comments. Significant differences were reported by specialty in student perception of benefit and reported time studying during the break. PMID- 27272425 TI - Rotation in a Smoking Cessation Clinic Improves Nicotine Dependence Treatment Provided by First-Year Internal Medicine Trainees. AB - BACKGROUND AND OBJECTIVES: Over 70% of smokers visit a physician annually, and physicians are well-positioned to assist patients in smoking cessation. Residency offers the ideal setting to train physicians in best practices for treatment of nicotine dependence. We hypothesized that experiential learning during a smoking cessation medical clinic (SCMC) rotation would be associated with an improvement in smoking cessation practice of internal medicine (IM) interns in outpatient primary care and inpatient settings. METHODS: This was a prospective study performed at a large university-affiliated hospital. Forty IM interns rotated through SCMC. After a lecture on nicotine addiction and treatment, interns treated SCMC patients under direct supervision of an attending pulmonologist. Interns' smoking cessation practices before and after SCMC rotation were evaluated through chart review over 1 year. Upon study completion, a survey to assess confidence was administered. Paired t tests measured changes in rates of identifying smokers, offering pharmacological treatment and counseling. RESULTS: A total of 5,622 outpatient and 683 inpatient charts of interns' encounters with patients were reviewed. Following SCMC rotation, there was an increase in identifying active smokers (7.1% versus 18.7%), prescribing therapy for smoking cessation (6.5% versus 18.0%), and providing counseling (30.9% versus 42.3%) to outpatients. For inpatients, there was an increase in nicotine replacement during admission (12.9% versus 37.4%) and prescription of therapy upon discharge (5.7% versus 16.1%). Interns reported confidence in providing appropriate counseling and treatment. CONCLUSIONS: SCMC experience positively impacted smoking cessation treatment by IM interns, causing a measurable change in their practice. PMID- 27272426 TI - Preparing Future Leaders: An Integrated Quality Improvement Residency Curriculum. AB - BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) has recognized the importance of quality improvement (QI) training and requires that accredited residencies in all specialties demonstrate that residents are "integrated and actively participate in interdisciplinary clinical quality improvement and patient safety activities." However, competing demands in residency training may make this difficult to accomplish. The study's objective is to develop and evaluate a longitudinal curriculum that meets the ACGME requirement for QI and patient safety training and links to patient centered medical home (PCMH) practices. METHODS: Residents in the Worcester Family Medicine Residency (WFMR) participated in a faculty-developed quality improvement curriculum that included web-based tutorials, quality improvement projects, and small-group sessions across all 3 years of residency. They completed self-evaluations of knowledge and use of curricular activities annually and at graduation, and comparisons were made between two graduating classes, as well as comparison of end of PGY2 to end of PGY3 for one class. RESULTS: Graduating residents who completed the full 3 years of the curriculum rated themselves as significantly more skilled in nine of 15 areas assessed at end of residency compared to after PGY2 and reported confidence in providing future leadership in a focus group. Five areas were also rated significantly higher than prior-year residents. CONCLUSIONS: Involving family medicine residents in a longitudinal curriculum with hands-on practice in implementing QI, patient safety, and chronic illness management activities that are inclusive of PCMH goals increased their self-perceived skills and leadership ability to implement these new and emerging evidence-based practices in primary care. PMID- 27272427 TI - Unsung Heroes Throughout the 2011 Fukushima Catastrophe. PMID- 27272429 TI - Spring Chicken: Staying Young Forever (Or Die Trying). PMID- 27272428 TI - Ordinary Medicine: Extraordinary Treatments, Longer Lives, and Where to Draw the Line. PMID- 27272430 TI - Passage. PMID- 27272431 TI - Parenting During Residency. PMID- 27272432 TI - Response to "Parenting During Residency". PMID- 27272433 TI - How a Virus Made Me a Better Leader. PMID- 27272434 TI - A biphasic calcium phosphate coating for potential drug delivery affects early osseointegration of titanium implants. AB - BACKGROUND: Calcium phosphate (CaP) surface coatings may accelerate osseointegration and serve as a drug delivery system for mineral-binding biomolecules. In a pilot study, the impact of a commercially available, thin CaP coating on early osseous bone remodeling was compared with a modern, subtractive treated rough surface (SLA-like) in an animal trial. METHODS: In 16 rabbits, 32 endosseous implants (CaP; n = 16, SLA-like; n = 16) were bilaterally inserted in the proximal tibia after randomization. After 2 and 4 weeks, bone-implant contact (BIC;%) in the cortical (cBIC) and the trabecular bone (sBIC) as well as volume of bone within the screw thread with the highest amount of new-formed bone (area;%) were analyzed. RESULTS: After 2 weeks, cBIC was significantly higher for CaP when compared with SLA-like (58 +/- 7% versus 40.4 +/- 18%; P = 0.021). sBIC for CaP was 14.7 +/- 8% and for SLA-like 7.2 +/- 7.8% (P = 0.081). For area, the mean volumes were 82.8 +/- 10.8% for CaP and 73.6 +/- 22% for SLA-like (P = 0.311). After 4 weeks, cBIC was 42.9 +/- 13% for the CaP and 46.5 +/- 29.1% for the SLA-like group (P = 0.775). An sBIC of 6.9 +/- 9.3% was calculated for CaP and of 12.3 +/- 4.8% for SLA-like (P = 0.202). The values for area were 62.3 +/- 24.1% for CaP and 50.1 +/- 25.9% for SLA-like (P = 0.379). CONCLUSIONS: The CaP coating has putative additional advantages in the early osseoconduction phases. It seems suitable for a feasible and clinical applicable bioactivation. PMID- 27272435 TI - Design, Synthesis, EPR-Studies and Conformational Bias of Novel Spin-Labeled DCC Analogues for the Highly Regioselective Labeling of Aliphatic and Aromatic Carboxylic Acids. AB - Novel types of spin-labeled N,N'-dicyclohexylcarbodiimides (DCC) are reported that bear a 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) residue on one side and different aromatic and aliphatic cyclohexyl analogues on the other side of the diimide core. These readily available novel reagents add efficiently to aliphatic and aromatic carboxylic acids, forming two possible spin-labeled amide derivatives with different radical distances of the resulting amide. The addition of aromatic DCC analogues proceeds with excellent selectivity, giving amides where the carboxylic acid is exclusively connected to the aromatic residue, while little or no selectivity was observed for the aliphatic congeners. The usefulness of these adducts in structural studies was demonstrated by EPR (electron paramagnetic resonance) measurements of biradical adducts of biphenyl-4,4' dicarboxylic acids. These analyses also reveal high degrees of conformational bias for aromatic DCC derivatives, which further underlines the powerfulness of these novel reagents. This observation was further corroborated by quantum chemical calculations, giving a detailed understanding of the structural dynamics, while detailed information on the solid state structure of all novel reagents was obtained by X-ray structure analyses. PMID- 27272436 TI - Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth. AB - Saw palmetto supplements (SPS) are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP) SPS >= 750 nM with testosterone significantly increased and >=500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP) SPS >= 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP) SPS >= 750 nM or with androgens significantly decreased LNCaP cell number (n = 3; p < 0.05). Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n = 4), HLLP, HLHP, and HMLP SPS (n = 6) groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p < 0.05). Results may suggest that SPS inhibit 5alpha-reductase thereby preventing hamster flank organ growth. PMID- 27272437 TI - UV-Triggered Surface-Initiated Polymerization from Colorless Green Tea Polyphenol Coated Surfaces. AB - A facile and versatile approach to constructing colorless surface coatings based on green tea polyphenols is reported, which can further act as a photoinitiating layer to initiate radical polymerization. These colorless green tea polyphenol coatings are capable of successfully photografting polymer brushes, and the resulting polymer brush patterns show spatial shape adjustability by masked UV irradiation. Both surface modifications and photografted polymer brushes do not alter the original color of the substrates. This method could be promising for the development of surface modifications. PMID- 27272438 TI - Performance in a GO/NOGO perceptual task reflects a balance between impulsive and instrumental components of behaviour. AB - In recent years, simple GO/NOGO behavioural tasks have become popular due to the relative ease with which they can be combined with technologies such as in vivo multiphoton imaging. To date, it has been assumed that behavioural performance can be captured by the average performance across a session, however this neglects the effect of motivation on behaviour within individual sessions. We investigated the effect of motivation on mice performing a GO/NOGO visual discrimination task. Performance within a session tended to follow a stereotypical trajectory on a Receiver Operating Characteristic (ROC) chart, beginning with an over-motivated state with many false positives, and transitioning through a more or less optimal regime to end with a low hit rate after satiation. Our observations are reproduced by a new model, the Motivated Actor-Critic, introduced here. Our results suggest that standard measures of discriminability, obtained by averaging across a session, may significantly underestimate behavioural performance. PMID- 27272439 TI - Heterogeneous nucleation of Al melt in symmetrical or asymmetrical confined nanoslits. AB - MD simulations are performed to study the solidification of Al melt in confined nanoslits (NSs) constructed by identical or different substrates, as well as on Fe substrates. Compared to the single substrate, the confined NS could promote the crystallization of Al melt, and its size has a significant impact on the solidified structure. In symmetrical NSs, liquid Al atoms would stack based on the atomic arrangement mode of the substrate, however in asymmetrical confined NSs, the atomic arrangement mode of liquid Al is governed by the constitution of asymmetrical substrates. Specifically, for the NS formed by Fe(110) and Fe(111) substrates, the induced region from the Fe(110) substrate is much bigger than that from Fe(111). Moreover, the freezing of liquid Al in asymmetrical NSs constructed from copper and iron has also been studied. These results throw light on heterogeneous nucleation in confined space. PMID- 27272440 TI - Cancerous glucose metabolism in lung cancer-evidence from exhaled breath analysis. AB - Cancer cells prefer hyperglycolysis versus oxidative phosphorylation, even in the presence of oxygen. This phenomenon is used through the FDG-PET scans, and may affect the exhaled volatile signature. This study investigates the volatile signature in lung cancer (LC) before and after an oral glucose tolerance test (OGTT) to determine if tumor cells' hyperglycolysis would affect the volatile signature. Blood glucose levels and exhaled breath samples were analyzed before the OGTT, and 90 min after, in both LC patients and controls. The volatile signature was measured by proton transfer reaction mass spectrometry (PTR-MS). Twenty-two LC patients (age 66.6 +/- 12.7) with adenocarcinoma (n = 14), squamous (n = 6), small cell carcinoma (n = 2), and twenty-one controls (age 54.4 +/- 13.7; 10 non-smokers and 11 smokers) were included. All LC patients showed a hyperglycolytic state in their FDG-PET scans. Both baseline and post OGTT volatile signatures discriminate between the groups. The OGTT has a minimal effect in LC (a decrease in m/z 54 by 39%, p v = 0.0499); whereas in the control group, five masses (m/z 64, 87,88, 142 and 161) changed by -13%, -49%, 40% and -29% and 46% respectively. To conclude, OGTT has a minimal effect on the VOC signature in LC patients, where a hyperglycolytic state already exists. In contrast, in the control group the OGTT has a profound effect in which induced hyperglycolysis significantly changed the VOC pattern. We hypothesized that a ceiling effect in cancerous patients is responsible for this discrepancy. PMID- 27272441 TI - The 'switch on-switch off model': Strategies used by nurses to mentally prepare and disengage from work. AB - There is considerable research on the experience of nurses during both their work and non-work time. However, we know relatively little about the strategies nurses use immediately before and immediately after their shift. This crossover period, from one shift to another, has critical impact for patient outcomes. The aim of this qualitative study was to explore strategies nurses employ to mentally prepare for their shift (switch on), and mentally disengage after the end of it (switch off). Eleven Greek hospital nurses were recruited for the study. Interviews were audio-taped and analysed using a content analysis approach. Five themes were identified as strategies nurses use to mentally prepare and disengage from their shift: (i) personal care/grooming; (ii) religious rituals; (iii) nicotine/caffeine; (iv) social interaction; and (v) listening to music. Nurses reported using the same strategies before and after their shift, but for different purposes. The authors propose a 'switch on-switch off' model to describe the process of mental preparation and mental disengagement from work. The switch-on/off approach represents an opportunity to increase nurses' resilience and identify individual and organizational factors that contribute to patient outcomes. PMID- 27272442 TI - Antioxidant, Antibacterial, and Antiproliferative Activities of Free and Bound Phenolics from Peel and Flesh of Fuji Apple. AB - This study was conducted to investigate the antioxidant, antibacterial, and antiproliferative activities of flesh free (FF), flesh bound (FB), peel free (PF), and peel bound (PB) phenolics from Fuji apple. The PB, which had highest total phenolic contents (126.15 +/- 2.41 mg/100 g wet weight) and lowest total carbohydrate contents (34.68 +/- 2.78 mg/100 g wet weight), showed the strongest 2,2'-azinobis-(3-ethylbenthiazoline-6-sulphonate) (ABTS) radical scavenging activity (EC50 = 0.36 +/- 0.02 mg/mL), 1,1-diphenyl-2-picryhydrazyl (DPPH) radical scavenging activity (EC50 = 0.26 +/- 0.01 mg/mL), and ferric reducing antioxidant power (Ferric reducing antioxidant power; EC50 = 0.19 +/- 0.02 mg/mL) compared with those of FF, FB, and PF. The PB also showed the strongest antibacterial activities on Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes and it also showed the highest antiproliferative effects on Caco-2 human colonic cancer cell (EC50 = 1.44 +/- 0.01 mg/mL) and Hela human cervical cell (EC50 = 2.81 +/- 0.01 mg/mL). Both free and bound phenolics from Fuji apple showed good antioxidant, antibacterial, and antiproliferative activities in our study, and bound phenolics had significantly higher activities compared with those of free phenolics. PMID- 27272443 TI - Focused extracorporeal shock wave for osteonecrosis of the femoral head with leukemia after allo-HSCT: a case series. PMID- 27272444 TI - Impact of KIR/HLA genetic combinations on double umbilical cord blood transplantation outcomes. Results of a French multicentric retrospective study on behalf of the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) and the Societe Francophone d'Histocompatibilite et d'Immunogenetique (SFHI). PMID- 27272445 TI - Management of refractory autoimmune hemolytic anemia via allogeneic stem cell transplantation. PMID- 27272446 TI - Haploidentical hematopoietic stem cell transplantation in children with high-risk hematologic malignancies: outcomes with two different strategies for GvHD prevention. Ex vivo T-cell depletion and post-transplant cyclophosphamide: 10 years of experience at a single center. AB - Forty patients with high-risk hematologic malignancies, median age 9 years, underwent haploidentical-HSCT from April 2005 to April 2015. Seventeen patients were transplanted with CD3-depleted PBSCs by negative selection (TCD group) following a reduced-intensity conditioning regimen (RIC), and 23 patients received T-cell-replete PBSCs followed by post-transplantation cyclophosphamide (PT-Cy group) after myeloablative conditioning (n=16) or RIC (n=7). Outcomes are reported for the TCD and PT-Cy recipients, respectively. Engraftment was achieved in 88% versus 100%. Median time to neutrophils>500/MUL was 10 days versus 15 days. Platelets>20 000/MUL occurred at a median of 16 days versus 20 days, respectively. Transplant-related mortality (TRM) was 24% versus 26% at 1 year. The cumulative incidence (CI) of grade III-IV acute GvHD was 7% versus 5%, and chronic GvHD 9% versus 53% (P=0.029). Relapse at 2 years was 31% versus 24%. Actuarial overall survival rates at 2 years were 47% versus 48%. Causes of death were infections (n=3), sinusoidal obstructive syndrome (n=4), acute GvHD (n=2) and relapse (n=9). These results indicate that haploidentical-HSCT is feasible in Uruguay. The TRM rate is of concern and should be the focus of continuing attention. Chronic GvHD risk was higher in the PT-Cy approach, so modifications are justified. PMID- 27272447 TI - High prevalence of small- and large-fiber neuropathy in a prospective cohort of patients with moderate to severe chronic GvHD. PMID- 27272449 TI - High incidence of severe chronic GvHD after HSCT with sibling donors. A single center analysis. PMID- 27272450 TI - Transplants for MDS and quality-of-life. But whose quality-of-life? PMID- 27272448 TI - Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning. AB - Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (follicle-stimulating hormone (FSH) level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12-45 years were evaluated (7 in the intervention group and 10 in the observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at a median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure. PMID- 27272451 TI - Unrelated donor search prognostic score to support early HLA consultation and clinical decisions. AB - A simple scoring system that can provide a quick search prognosis at the onset of an adult unrelated donor (URD) search could be a useful tool for transplant physicians. We aimed to determine whether patient human leukocyte Ag genotype frequency (GF) could be used as a surrogate measure of whether or not a potential 10/10 and/or 9/10 URD in the Be The Match Registry (BTMR) can be identified for the patient. GF was assigned on a training data set of 2410 patients that searched the BTMR using the reported ethnic group. A proportional odds model was used to correlate GF with defined search productivity categories as follows: 'Good' (>2 10/10), 'Fair' (1-2 10/10 or No 10/10 and >2 9/10) or 'Poor' (No 10/10 and <3 9/10). A second cohort (n=2411) was used to calculate the concordance by the ethnic group in all three categories. In addition, we validated against an independent cohort (n=1344) resolved as having a 10/10 or 9/10 matched URD. Across the ethnic groups, >90% of cases with 'Good' GF prognosis, 20-26% 'Fair' and <10% 'Poor' had a 10/10 URD. Although not a replacement for an actual URD search, GF offers a quick way for transplant physicians to get an indication of the likely search outcome. PMID- 27272452 TI - Risk of serious bloodstream infections is low in pediatric hematopoietic stem cell transplant (HSCT) recipients with fevers due to antithymocyte globulins and alemtuzumab. PMID- 27272453 TI - The impact of hepatitis B core antibody levels on HBV reactivation after allogeneic hematopoietic SCT: an 11-year experience at a single center. PMID- 27272455 TI - Influence of the calf presence during milking on dairy performance, milk fatty acid composition, lipolysis and cheese composition in Salers cows during winter and grazing seasons. AB - The milking of Salers cows requires the presence of the calf. The removal of the calf would simplify the milking routine, but it could also modify the milk yield and the milk and cheese composition. Therefore, the aim of this experiment was to evaluate the effect of calf presence during milking during sampling period (winter or grazing periods), on dairy performance, milk fatty acid (FA) composition, lipolysis and cheese yield and composition. Nine and 8 Salers lactating cows were milked in the presence (CP) or absence (CA) of their calves respectively. During winter, the cows were fed a hay-based diet and then they only grazed a grassland pasture. Calf presence during milking increased milk yield and milk 16:0 concentration and decreased milk fat content and milk total odd- and branched-chain FA (OBCFA) concentrations. Calf presence only increased initial lipolysis in milk collected during the winter season. Milk from CP cows compared to CA cows resulted in a lower cheese yield and ripened cheeses with lower fat content. Milk from the grazing season had lower saturated medium-chain FA and OBCFA concentrations and higher 18:0, cis-9-18:1, trans-11-18:1 and cis-9, trans-11-CLA concentrations than that from the winter season. Initial milk lipolysis was higher in the winter than in the grazing season. These variations could be due to seasonal changes in the basal diet. Furthermore, the effect of calf presence during milking on milk fat composition was lower than that on dairy performance, cheese yield and composition. Removing the calf during the milking of Salers cows seems feasible without a decrease in milked milk, and with a positive effect on cheese yield and fat content, under the condition that we are able to select cows having the capacity to be milked easily without the calf. PMID- 27272456 TI - Desmoplastic melanoma presenting as primary alopecia neoplastica: a report of two cases. AB - Desmoplastic melanoma is an uncommon form of melanoma characterized by atypical spindled melanocytes and abundant collagen deposition. It typically presents in sun-damaged skin of the elderly as an amelanotic, indurated lesion. It has a higher tendency for local recurrence but lower risk of lymph node metastasis vs. conventional malignant melanoma. We report two cases in women aged 59 and 66 who presented with small scalp lesions clinically suggestive of alopecia. The differential diagnosis included alopecia areata, lupus erythematosus and lichen planopilaris. Biopsies performed according to alopecia protocol were reviewed at our institutions. Biopsies revealed atypical spindled and nested epithelioid melanocytes set in a sclerotic dermis with scattered lymphoid aggregates and immunohistochemical expression of S100 protein, features diagnostic of combined desmoplastic melanoma. Wide local excision with skin graft was performed on the older patient. Excision showed combined desmoplastic melanoma with a Breslow thickness of 8.5 mm with melanoma in situ identified in the adjacent epidermis. The other patient sought treatment elsewhere and was lost to follow up. These cases illustrate desmoplastic melanoma as an unusual etiology and dangerous clinical pitfall in patients with scar-like alopecia. To the authors' knowledge, these represent the second and third reported cases of desmoplastic melanoma presenting as primary alopecia neoplastica. PMID- 27272454 TI - Up-to-date tools for risk assessment before allogeneic hematopoietic cell transplantation. AB - Cure of malignant and non-malignant hematological diseases is potentially possible after allogeneic hematopoietic stem cell transplantation (HCT). Accurate evaluation of the risk-benefit ratio for an individual patient could improve the decision-making process about transplant, which ultimately would increase the likelihood of success. Several transplant-related models were designed in an effort to optimize decision-making about suitable candidates for allogeneic HCT. In 1998, The European Society for Blood and Marrow Transplantation (EBMT) developed a five-component pretransplantation risk scoring system for patients with CML. The EBMT score was later tested in patients with various hematological disorders, and it was shown to stratify risks of mortality after allogeneic HCT. More recent research efforts focused on models that assess health status before HCT. A HCT-specific comorbidity index was designed to assign weights to 17 relevant comorbidities that were shown to independently predict non-relapse mortality. Performance status scales and comprehensive geriatric assessment tools might uncover additional overall health limitations that affect long-term survival among older recipients of allogeneic HCT. Other models include the pretransplantation assessment of mortality score that summarizes the impacts of eight different pretransplantation patient- and disease-specific variables into a 50-point model that predicts survival. The disease-risk index captures the impact of primary diagnoses and disease status on relapse and survival following allogeneic HCT. The values and limitations of each model are discussed herein. We also provide insight on how to use these models in the clinic to decide about offering allogeneic HCT with the most suitable conditioning regimen intensity. PMID- 27272457 TI - An ultrasensitive "on-off-on" photoelectrochemical aptasensor based on signal amplification of a fullerene/CdTe quantum dots sensitized structure and efficient quenching by manganese porphyrin. AB - In this work, an ultrasensitive "on-off-on" photoelectrochemical (PEC) aptasensor was proposed based on the signal amplification of a fullerene/CdTe quantum dot (nano-C60/CdTe QDs) sensitized structure and efficient signal quenching of nano C60/CdTe QDs by a manganese porphyrin (MnPP). PMID- 27272458 TI - [40]pi Fused and Nonfused Core-Modified Nonaphyrins: Syntheses and Structural Diversity. AB - The synthesis of fused and nonfused core-modified 40pi nonaphyrins are reported. Spectroscopic and X-ray structural studies reveal a twisted figure-eight conformation in the freebase form that is nonaromatic. Structural changes occur, from figure-eight to open extended conformation, upon protonation, thereby adopting 4npi Huckel antiaromatic character, which is reflected in spectroscopic and theoretical studies. Such a structural change also induces ring inversions of specific heterocyclic rings by 180 degrees . PMID- 27272460 TI - Structural studies and SH3 domain binding properties of a human antiviral salivary proline-rich peptide. AB - Human saliva contains hundreds of small proline-rich peptides originated by the proteolytic cleavage of the salivary basic Proline-Rich Proteins. Nevertheless only for few of them a specific biological activity has been assigned to date. Among them, the 1932 Da peptide (p1932) has been patented as an anti-HIV agent. In order to shed light on the possible mechanism of action of this peptide, we assessed in this study, by means of molecular dynamics calculations, circular dichroism and FTIR spectroscopic techniques, that p1932 has an intrinsic propensity to adopt a polyproline-II helix arrangement. This structural feature combined with the presence of PxxP motifs in its primary structure, represents an essential property for the exploitation of several biological activities. Next to these findings, we recently demonstrated the ability of this peptide to be internalized within cells of the oral mucosa, thus we focused onto a possible intracellular target, represented by the SH3 domains family. Its ability to interact with selected SH3 domains was finally assayed by Surface Plasmon Resonance spectroscopy. As a result, only Fyn, Hck, and c-Src SH3 domains gave positive results in terms of interaction, showing dissociation constants ranging from nanomolar to micromolar values having the best performer a KD of 148 nM. It is noteworthy that all the interacting domains belong to the Src kinases family, suggesting a role for p1932 as a modulator of the signal transduction pathways mediated by these kinases. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 714-725, 2016. PMID- 27272459 TI - Nanomaterial datasets to advance tomography in scanning transmission electron microscopy. AB - Electron tomography in materials science has flourished with the demand to characterize nanoscale materials in three dimensions (3D). Access to experimental data is vital for developing and validating reconstruction methods that improve resolution and reduce radiation dose requirements. This work presents five high quality scanning transmission electron microscope (STEM) tomography datasets in order to address the critical need for open access data in this field. The datasets represent the current limits of experimental technique, are of high quality, and contain materials with structural complexity. Included are tomographic series of a hyperbranched Co2P nanocrystal, platinum nanoparticles on a carbon nanofibre imaged over the complete 180 degrees tilt range, a platinum nanoparticle and a tungsten needle both imaged at atomic resolution by equal slope tomography, and a through-focal tilt series of PtCu nanoparticles. A volumetric reconstruction from every dataset is provided for comparison and development of post-processing and visualization techniques. Researchers interested in creating novel data processing and reconstruction algorithms will now have access to state of the art experimental test data. PMID- 27272472 TI - Development of on-chip fully automated immunoassay system "MUTASWako i30" to measure the changes in glycosylation profiles of alpha-fetoprotein in patients with hepatocellular carcinoma. AB - Glycosylation profiles significantly change during oncogenesis. Aberrant glycosylation can be used as a cancer biomarker in clinical settings. Different glycoforms can be separately detected using lectin affinity electrophoresis and lectin array-based methods. However, most methodologies and procedures need experienced technique to perform the assays and expertise to interpret the results. To apply glycomarkers for clinical practice, a robust assay system with an easy-to-use workflow is required. Wako's MUTASWako i30, a fully automated immunoanalyzer, was developed for in vitro diagnostics based on microfluidic technology. It utilizes the principles of liquid-phase binding assay, where immunoreactions are performed in a liquid phase, and electrokinetic analyte transport assay. Capillary electrophoresis on microfluidic chip has enabled the detection of different glycoform types of alpha-fetoprotein (AFP), a serum biomarker for hepatocellular carcinoma. AFP with altered glycosylation can be separated based on the reactivity to Lens culinaris agglutinin on electrophoresis. The glycoform AFP-L3 was reportedly more specific in hepatocellular carcinoma. This assay system can provide a high sensitivity and rapid results in 9 min. The test results for ratio of AFP-L3 to total AFP using MUTASWako i30 are correlated with those of conventional methodology. The MUTASWako assay system and the technology can be utilized for glycosylation analysis in the postgenomic era. PMID- 27272473 TI - Improving Memory and Cognition in Individuals with Down Syndrome. AB - Down syndrome (DS), often due to trisomy 21, is the most common genetic cause of intellectual disability (ID). In addition, virtually all individuals with DS develop the neuropathology of Alzheimer's disease (AD) by the age of 40 years and almost 60 % will manifest symptoms of AD dementia by the age of 65 years. Currently, there are no pharmacological treatments available for ID in individuals with DS and only limited symptomatic treatments for AD dementia. Advances in our understanding in both the molecular basis of ID and the pathogenesis of AD have created opportunities to study potential therapeutic targets. Recent studies in animal models of DS continue to provide a rational basis for translating specific compounds into human clinical trials. However, target and compound selection are only initial steps in the drug development pathway. Other necessary considerations include appropriate study designs to assess efficacy in the DS population, as well as operational aspects specifically tailored to assess cognition in this population. We discuss recent progress in the development of compounds for both ID and AD in individuals with DS, as well as concepts for the design and conduct of clinical trials with such compounds. PMID- 27272474 TI - Long non-coding RNA LINC00628 functions as a gastric cancer suppressor via long range modulating the expression of cell cycle related genes. AB - To discover new biomarkers for gastric cancer (GC) diagnose and treatment, we screened the lncRNAs in GC tissues from 5 patients. We found 6 lncRNAs had altered expression, and in the same time, the levels of their neighboring genes (located near 300 kb upstream or downstream of lncRNA locus) were significantly changed. After confirming the results of microarray by qRT-PCR in 82 GC patients, the biological function of LINC00628 was examined through cell proliferation and apoptosis, cell migration and invasion, colony formation assay and cell cycle detection. We confirmed that LINC00628 functions as a GC suppressor through suppressing proliferation, migration and colony formation of cancer cells. Furthermore, LINC00628 can also suppress the tumor size in mouse xenograft models. Although LINC00628 can modulate LRRN2 expression, the GC suppressor function of LINC00628 is not LRRN2 dependent. The result of mRNA microarray indicated that LINC00628 perform GC inhibitor function through long-range modulating cell cycle related genes. Importantly, we confirmed that LINC00628 mainly located in the nucleus and interacted with EZH2, and modulated genes expression by regulating H3K27me3 level. This research shed light on the role of dysregulated LINC00628 during GC process and may serve as a potential target for therapeutic intervention. PMID- 27272475 TI - "Drug-resistant granuloma faciale": treatment with carbon dioxide-GaAs laser. AB - Granuloma faciale (GF), also known as "eosinophilic granuloma," is a rare benign leukocytoclastic vasculitis which most commonly occurs on the face of middle-aged Caucasian males. Clinically, GF appears as single or multiple, slowly growing, reddish-brown papules, nodules or plaques which may be cosmetically unpleasant. Its pathogenesis is unknown and GF is notoriously resistant to treatments. Both medical (dapsone, colchicine, gold injections, isoniazid, clofazimine, corticosteroids, psoralen ultraviolet radiation, and topical tacrolimus) and surgical therapies (excision, graft, dermabrasion, argon laser, carbon dioxide laser, pulsed dye laser, cryotherapy, and electrosurgery) have been used for GF but no effective treatment has yet been found. Furthermore, the typical facial location of GF requires an acceptable cosmetic result. We report two cases of drug-resistant GF which were successfully treated with laser vaporization combining two different wavelengths: carbon dioxide (CO2 ) 10,600 nm and GaAs 1540 nm. PMID- 27272476 TI - Suicide Rates and Methods in Active Duty Military Personnel, 2005 to 2011: A Cohort Study. AB - BACKGROUND: Suicide prevention programs have become ubiquitous among military units; identifying temporal trends and nonclinical factors associated with the chosen suicide methods may help improve suicide prevention strategies. OBJECTIVE: To calculate suicide rates of active duty military personnel and identify those who are at risk for firearm-specific suicide. DESIGN: Retrospective cohort study. SETTING: Military units in the United States. PATIENTS: All active duty enlisted U.S. military personnel from 2005 to 2011. MEASUREMENTS: Suicide rates per 100 000 were calculated for each branch. Adjusted odds ratios for firearm-specific suicide were calculated with 95% CIs. RESULTS: 1455 military personnel committed suicide from 2005 to 2011. From 2006 to 2011, the rates were highest among army personnel (19.13 to 29.44 cases per 100 000). Among suicides with a known cause of death, 62% were attributed to firearms. The results of this study also suggest that among army personnel or marines who committed suicide, those with infantry or special operations job classifications were more likely than those in noninfantry positions to use a firearm. LIMITATIONS: Results are generalizable only to enlisted personnel and reflect only stateside suicides. Data regarding previous psychiatric illness, deployment history, and firearms ownership were lacking. CONCLUSION: These results may help inform policymakers and advisors about differences in risks of suicide and violent suicide among the armed services and may help guide efforts to prevent self-harm within the military. PRIMARY FUNDING SOURCE: None. PMID- 27272477 TI - Structural properties of geminal dicationic ionic liquid/water mixtures: a theoretical and experimental insight. AB - The structural behavior of geminal dicationic ionic liquid 1,n-bis[3 methylimidazolium-1-yl] alkane bromide ([Cn(mim)2]Br2)/water mixtures has been studied using extended X-ray absorption fine structure (EXAFS) spectroscopy in combination with molecular dynamics (MD) simulations. The properties of the mixtures are investigated as a function of both water concentration and alkyl bridge chain length. The very good agreement between the EXAFS experimental data and the theoretical curves calculated from the MD structural results has proven the validity of the theoretical framework used for all of the investigated systems. In all the solutions the water molecules are preferentially coordinated with the Br(-) ion, even if a complex network of interactions among dications, anions and water molecules takes place. The local molecular arrangement around the bromide ion is found to change with increasing water content, as more and more water molecules are accomodated in the Br(-) first coordination shell. Moreover, with the decrease of the alkyl-bridge chain length, the interactions between dications and anions increase, with Br(-) forming a bridge between the two imidazolium rings of the same dication. On the other hand, in [Cn(mim)2]Br2/water mixtures with long alkyl-bridge chains peculiar internal arrangements of the dications are found, leading to different structural features of geminal dicationic ionic liquids as compared to their monocationic counterparts. PMID- 27272478 TI - Structure characterization of the non-crystalline complexes of copper salts with native cyclodextrins. AB - The characterization of non-crystalline complexes is particularly difficult when techniques like X-ray diffraction or NMR cannot be used. We propose a simple procedure to characterize the physicochemical properties of amorphous new coordination compounds between cyclodextrins (CD) and Cu(2+) salts, by means of the integration of the information provided by several techniques including elemental analysis, flame atomic absorption, TGA, UV-Vis diffuse reflectance, colorimetry, FT-IR and EPR. On the basis of these procedures, we suggest geometrical and structural approximations resulting in an octahedral or distorted octahedral geometry with diverse positions for the metallic centre. According to the EPR spectrum, only one of the complexes may have rhombic symmetry. We also analyzed enthalpy-entropy compensation and the isokinetic effect. In addition, general trends in thermal stability, spectroscopic properties and inclusion in the cavity were analysed. This complete characterization methodology becomes essential for their future application as catalysts. PMID- 27272479 TI - Editor's Note. PMID- 27272480 TI - Neural Monitoring in Thyroid Surgery: Is It Evidence Based? Is It Cost Effective?: Reply. PMID- 27272481 TI - Prognostic Impact of Further Treatments on Distant Metastasis in Patients With Minimally Invasive Follicular Thyroid Carcinoma: Verification Using Inverse Probability of Treatment Weighting. AB - BACKGROUND: The aim of this study was to evaluate the prognostic impact of further treatments in minimally invasive follicular thyroid carcinoma (MIFTC) patients. METHODS: The risk factors for distant metastases were analyzed, and the impact of surgical extent on distant metastasis was verified by using weighted logistic regression models with inverse-probability of treatment weighting (IPTW). RESULTS: 166 patients including 31 males (18.7 %) and 135 females (81.3 %), with the mean age of 41.5 +/- 13.5 years, were enrolled for this study. The median follow-up period was 103.5 months (range, 13-244 months). Seven patients (4.2 %) had distant metastases during follow-up period. The presence of vascular invasion (Hazard ratio [HR] = 29.06; 95 % Confidence Interval [CI] = 3.06-209.08; p = 0.015) and extensive vascular invasion >=4 foci (HR = 40.57; 95 % CI = 2.09 789.13; p = 0.014) were the independent risk factors for distant metastasis by multivariate analysis. Surgical extent did not influence distant metastasis. Logistic regression with IPTW also demonstrated that there were no statistically significant differences in the development of distant metastasis based on surgical extent (HR = 1.28; 95 % CI = 0.15-10.87; p = 0.823). CONCLUSIONS: The presence of extensive vascular invasion is the most powerful predictor of distant metastasis. However, it is noteworthy that further treatments do not demonstrate an advantageous effect on preventing distant metastasis during the follow-up period. PMID- 27272483 TI - Health Extension Workers' Knowledge and Knowledge-Sharing Effectiveness of Optimal Infant and Young Child Feeding Are Associated With Mothers' Knowledge and Child Stunting in Rural Ethiopia. AB - BACKGROUND: Little is known about how the knowledge and the knowledge-sharing effectiveness (KSE) of health extension workers (HEWs) affect maternal knowledge of optimal infant and young child feeding (IYCF) and their child's nutritional status. OBJECTIVE: The objective of this study was to evaluate mothers' and HEWs' knowledge of key IYCF practices and to investigate whether mothers' knowledge and HEWs' KSE are associated with stunting in young children (aged 12-23 months). METHODS: This cross-sectional study used face-to-face interviews to assess the IYCF knowledge of HEWs (n = 96) and mothers of 12- to 23-month-old children (n = 122) in Mecha district, West Gojam, Ethiopia. The association between HEWs' KSE and children's length-for-age z scores (LAZ) was investigated. RESULTS: Stunting (50%), underweight (34%), and wasting (10%) were highly prevalent. Less than half (45%) of the mothers had access to nutrition education through the health extension program, but those who had, had better knowledge of IYCF practices and thus lower rates of stunting ( P < .001). However, key IYCF practices were not well understood by the HEWs and this affected their KSE. The gap in KSE was negatively associated with LAZ ( r = -.475, P < .001) and remained significant even after adjusting for maternal height, socioeconomic status, and maternal education ( r = -.423, P = .002). CONCLUSION: Health extension workers' KSE is associated with child stunting. Future training of HEWs would benefit from emphasis on not only the content of the IYCF messages but also the process of delivery while increasing their counseling skills. PMID- 27272482 TI - Sarcopenia/Muscle Mass is not a Prognostic Factor for Short- and Long-Term Outcome After Esophagectomy for Cancer. AB - BACKGROUND: Recent studies have suggested that sarcopenia is a prognostic risk indicator of postoperative complications and predicts survival in cancer patients. The aim of this study is to investigate whether sarcopenia is associated with postoperative short-term outcome (morbidity and mortality) and long-term survival in patients undergoing esophagectomy for cancer after neoadjuvant chemoradiotherapy. METHODS: All patients who underwent neoadjuvant chemoradiotherapy followed by esophagectomy for cancer, and of whom an adequate CT scan was available, were included in the current study. The presence of sarcopenia was defined by CT imaging using cut-off values of the total cross sectional muscle tissue measured transversely at the third lumbar level. RESULTS: A total number of 120 patients were eligible for analysis. Almost half of the patients (N = 54, 45 %) were classified as having sarcopenia; 24 sarcopenic patients (44 %) had overweight and 5 sarcopenic patients (9 %) were obese. Overall morbidity and mortality rate did not differ significantly between sarcopenic and non-sarcopenic patients, nor did long-term overall or disease-free survival. Also sarcopenic obesity was not associated with worse outcome. CONCLUSION: The presence of sarcopenia was not associated with a negative short- and long-term outcome in this selected group of esophageal cancer patients after neoadjuvant chemoradiotherapy followed by esophagectomy. PMID- 27272484 TI - Managing Risk After Intracerebral Hemorrhage in Concomitant Atrial Fibrillation and Cerebral Amyloid Angiopathy. PMID- 27272485 TI - Hemorrhagic Reversible Cerebral Vasoconstriction Syndrome: Features and Mechanisms. AB - BACKGROUND AND PURPOSE: To compare hemorrhagic and nonhemorrhagic reversible cerebral vasoconstriction syndromes (RCVS) with a view to understand mechanisms. METHODS: This single-center retrospective study included 162 patients with RCVS. Clinical, brain imaging, and angiography data were analyzed. RESULTS: The mean age was 44+/-13 years, 78% women. Hemorrhages occurred in 43% including 21 patients with intracerebral hemorrhage (ICH) and 62 with convexal subarachnoid hemorrhage (cSAH). The frequency of triggers (eg, vasoconstrictive drugs) and risk factors (eg, migraine) were not significantly different between hemorrhagic and nonhemorrhagic RCVS or between subgroups (ICH versus non-ICH, isolated cSAH versus normal scan). Hemorrhagic lesions occurred within the first week, whereas infarcts and vasogenic edema accumulated during 2 to 3 weeks (P<0.001). Although all ICHs occurred before cSAH, their time course was not significantly different (P=0.11). ICH and cSAH occurred earlier than infarcts (P<=0.001), and ICH earlier than vasogenic edema (P=0.009). Angiogram analysis showed more severe vasoconstriction in distal versus proximal segments in all lesion types (ICH, cSAH, infarction, vasogenic edema, and normal scan). The isolated infarction group had more severe proximal vasoconstriction, and those with normal imaging had significantly less vasoconstriction. Multivariable analysis failed to uncover independent predictors of hemorrhagic RCVS; however, female sex predicted ICH (P=0.048), and angiographic severity predicted infarction (P=0.043). CONCLUSIONS: ICH and cSAH are common complications of RCVS. Triggers and risk factors do not predict lesion subtype but may alter central vasomotor control mechanisms resulting in centripetal angiographic evolution. Early distal vasoconstriction is associated with lobar ICH and cSAH, and delayed proximal vasoconstriction with infarction. PMID- 27272486 TI - Added Value of Vessel Wall Magnetic Resonance Imaging in the Differentiation of Moyamoya Vasculopathies in a Non-Asian Cohort. AB - BACKGROUND AND PURPOSE: Although studies have evaluated the differential imaging of moyamoya disease and atherosclerosis, none have investigated the added value of vessel wall magnetic resonance imaging (MRI). This study evaluates the added diagnostic value of vessel wall MRI in differentiating moyamoya disease, atherosclerotic-moyamoya syndrome (A-MMS), and vasculitic-MMS (V-MMS) with a multicontrast protocol. METHODS: We retrospectively reviewed the carotid artery territories of patients with clinically defined vasculopathies (moyamoya disease, atherosclerosis, and vasculitis) and steno-occlusive intracranial carotid disease. Two neuroradiologists, blinded to clinical data reviewed the luminal imaging of each carotid, evaluating collateral extent and making a presumed diagnosis with diagnostic confidence. After 3 weeks, the 2 readers reviewed the luminal imaging+vessel wall MRI for the presence, pattern and intensity of postcontrast enhancement, T2 signal characteristics, pattern of involvement, and presumed diagnosis and confidence. RESULTS: Ten A-MMS, 3 V-MMS, and 8 moyamoya disease cases with 38 affected carotid segments were included. There was significant improvement in diagnostic accuracy with luminal imaging+vessel wall MRI when compared with luminal imaging (87% versus 32%, P<0.001). The most common vessel wall MRI findings for moyamoya disease were nonenhancing, nonremodeling lesions without T2 heterogeneity; for A-MMS eccentric, remodeling, and T2 heterogeneous lesions with mild/moderate and homogeneous/heterogeneous enhancement; and for V-MMS concentric lesions with homogeneous, moderate enhancement. Inter-reader agreement was moderate to substantial for all vessel wall MRI characteristics (kappa=0.46-0.86) and fair for collateral grading (kappa=0.35). There was 11% inter-reader agreement for diagnosis on luminal imaging when compared with 82% for luminal imaging+vessel wall MRI (P<0.001). CONCLUSIONS: Vessel wall MRI can significantly improve the differentiation of moyamoya vasculopathies when combined with traditional imaging techniques. PMID- 27272487 TI - Prehospital Acute Stroke Severity Scale to Predict Large Artery Occlusion: Design and Comparison With Other Scales. AB - BACKGROUND AND PURPOSE: We designed and validated a simple prehospital stroke scale to identify emergent large vessel occlusion (ELVO) in patients with acute ischemic stroke and compared the scale to other published scales for prediction of ELVO. METHODS: A national historical test cohort of 3127 patients with information on intracranial vessel status (angiography) before reperfusion therapy was identified. National Institutes of Health Stroke Scale (NIHSS) items with the highest predictive value of occlusion of a large intracranial artery were identified, and the most optimal combination meeting predefined criteria to ensure usefulness in the prehospital phase was determined. The predictive performance of Prehospital Acute Stroke Severity (PASS) scale was compared with other published scales for ELVO. RESULTS: The PASS scale was composed of 3 NIHSS scores: level of consciousness (month/age), gaze palsy/deviation, and arm weakness. In derivation of PASS 2/3 of the test cohort was used and showed accuracy (area under the curve) of 0.76 for detecting large arterial occlusion. Optimal cut point >=2 abnormal scores showed: sensitivity=0.66 (95% CI, 0.62 0.69), specificity=0.83 (0.81-0.85), and area under the curve=0.74 (0.72-0.76). Validation on 1/3 of the test cohort showed similar performance. Patients with a large artery occlusion on angiography with PASS >=2 had a median NIHSS score of 17 (interquartile range=6) as opposed to PASS <2 with a median NIHSS score of 6 (interquartile range=5). The PASS scale showed equal performance although more simple when compared with other scales predicting ELVO. CONCLUSIONS: The PASS scale is simple and has promising accuracy for prediction of ELVO in the field. PMID- 27272488 TI - Chicks produced in the Magellanic penguin (Spheniscus magellanicus) after cloacal insemination of frozen-thawed semen. AB - The in vitro and in vivo functionality of cryopreserved spermatozoa was examined over two breeding seasons in a zoological colony of Magellanic penguins (Spheniscus magellanicus). Frozen-thawed semen was inseminated into five anesthetized females, over a total of eight egg production cycles, with a different male used for each artificial insemination (AI) within each season. Females were maintained within the colony in cordoned nest sites to prevent copulation with their paired male, and were inseminated every 3-10 days until the first oviposition. Semen frozen from seven males using a straw method retained 39.8%, 25.7%, 74.0%, and 52.1% of its initial total motility, progressive motility, average path velocity, and plasma membrane integrity, respectively. Normal morphology of motile cells was reduced (P < 0.05) during freeze-thawing from 76.7% immediately prior to freezing to 65.3% post-thawing. Conceptive females received 1.6 +/- 0.2 inseminations before the first oviposition, with 19.2 +/- 1.6 * 10(6) motile, morphologically normal spermatozoa per insemination. Overall fertility was 53.3% (8/15 eggs), hatchability was 50.0% (4/8), and genetic analyses confirmed that all embryos and hatchlings were sired by the AI male. Fertile eggs were laid at 4.0-12.1 days after AI, indicating that frozen thawed spermatozoa resided in the female reproductive tract for up to ~7.2 days prior to fertilization. Results demonstrate that frozen-thawed Magellanic penguin spermatozoa are fully functional in vivo and support the use of genome banking and AI as tools for managing the sustainability of zoological penguin populations. Zoo Biol. 35:326-338, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272491 TI - Robotic-guided sacro-pelvic fixation using S2 alar-iliac screws: feasibility and accuracy. AB - PURPOSE: To review our experience with robotic guided S2-alar iliac (S2AI) screw placement. METHODS: We retrospectively reviewed patients who underwent S2AI fixation with robotic guidance. Screw placement and deviation from the preoperative plan were assessed by fusing preoperative CT (with the planned S2AI screws) to postoperative CT. The software's measurement tool was used to compare the planned vs. actual screw placements in axial and lateral views, at entry point to the S2 pedicle and at a 30 mm depth at the screws' mid-shaft, in a resolution of 0.1 mm. Medical charts were reviewed for technical issues and intra operative complications. RESULTS: 35 S2AI screws were reviewed in 18 patients. The patients' mean age was 60 years. No intra-operative complications that related to the placement of S2AI screws were reported and robotic guidance was successful in all 35 screws. Post-operative CT scans showed that all trajectories were accurate. No violations of the iliac cortex or breaches of the anterior sacrum were noted. At the entry point, the screw deviated from the pre-operative plan by 3.0 +/- 2.2 mm in the axial plane and 1.8 +/- 1.6 mm in the lateral plane. At 30 mm depth, the screw deviated from the pre-operative plan by 2.1 +/- 1.3 mm in the axial plane and 1.2 +/- 1.1 mm in the lateral plane. CONCLUSIONS: Robotic guided S2AI screw placement is feasible and accurate. No screw malpositions or complications that related to the placement of S2AI screws occurred in this series. Larger studies are needed to assess the long-term clinical outcomes of robotic guided sacral-pelvic fixation. PMID- 27272489 TI - Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data. AB - Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year follow up. Replicates of selected samples were measured at both time points to identify technical variability. Deming regression, Passing-Bablok regression, linear mixed models, non-linear models as well as ReplicateRUV and ComBat were applied to eliminate batch effects between replicates. In a second step, quantile normalization prior to batch effect correction was performed for each method. Technical variation between batches was evaluated by principal component analysis. Associations between body mass index and transcriptomes were calculated before and after batch removal. Results from association analyses were compared to evaluate maintenance of biological variability. Quantile normalization, separately performed in each batch, combined with ComBat successfully reduced batch effects and maintained biological variability. ReplicateRUV performed perfectly in the replicate data subset of the study, but failed when applied to all samples. All other methods did not substantially reduce batch effects in the replicate data subset. Quantile normalization plus ComBat appears to be a valuable approach for batch correction in longitudinal gene expression data. PMID- 27272492 TI - The impact of pelvic balance, physical activity, and fear-avoidance on the outcome after decompression and instrumented fusion for degenerative lumbar stenosis. AB - PURPOSE: To evaluate the impact of pelvic balance, physical activity, and fear avoidance in a cohort of patients undergoing decompression and instrumented fusion for degenerative lumbar stenosis. MATERIALS AND METHODS: This study includes consecutive patients undergoing decompression and instrumented fusion for degenerative lumbar stenosis by one main surgeon from January 2014 to January 2015. Patients were interviewed by a psychologist and underwent standing whole spine X-ray. Lumbar and pelvic parameters (PI, SS, PT, iPT, LL) were measured by an independent spinal surgeon. Physical activity was measured with the International Physical Activity Questionnaire (IPAQ). The "fear-avoidance" was measured with the Tampa Scale for Kinesiophobia (TSK). Back pain was assessed by the Graphic Rating Scale (GRS). The disability was assessed by the Roland-Morris Low Back Pain and Disability Questionnaire. Statistical interpretation of the data was performed using SPSS v19 software (SPSS Inc, Chicago, Illinois). RESULTS: The sample included 51 patients underwent standard posterior laminectomy and instrumented fusion. Surgery has a positive global impact on the perceived low back pain. No significant (Spearman) correlations emerged among pelvic parameters and the pre- and post-surgical GSR. Patients were divided into three groups according to the IPAQ scores after the operation: "inactive" (I), "minimally inactive" (m-I), and "HEPA". Significant differences emerged between IPAQ and Roland-Morris scores (F(2, 48) = 5.48, p = 0.007): the "inactive" (M(R M) = 11.3) or "minimally active" (M(R-M) = 9.8) groups scored significantly higher than the "HEPA" group (M(R-M) = 4.7). Tampa scores correlated with gender (rho = -0.408, p = 0.003) and with BMI (rho = -0.369, p = 0.008). Females and obese patients reported higher levels of Tampa scores. Significant relationship was found between Tampa scores and pre-GSR (rho(pre) = 0.250, p = 0.08) and significant with post-surgical GSR (rho(post) = 0.275, p = 0.05) and with post Roland-Morris score (rho(post) = 0.599, p < 0.01). CONCLUSION: The fear-avoidance and the physical inactivity are related to the highest levels of low back pain, more than pelvic imbalance. "Inactive" and "fear-avoidant" patients have also the worst outcome after surgery and the worst level of disability. PMID- 27272493 TI - Does right lateral decubitus position change retroperitoneal oblique corridor? A radiographic evaluation from L1 to L5. AB - PURPOSE: To determine if the retroperitoneal oblique corridor will be affected by right lateral decubitus position. METHODS: Forty volunteers were randomly enrolled and MRI scan was performed from L1 to L5 in supine and right lateral decubitus positions, respectively. In images across the center of each disc, O was defined as the center of a disc and A (supine) or A' (right lateral decubitus) was located in left lateral border of the aorta or the iliac artery; B (supine) or B' (right lateral decubitus) was on the anterior medial border of the psoas. The distance of AB and A'B' (Recorded as A-Ps and A-Pr, respectively) at each level was recorded and compared to each other. The relationships between A Pr, sex, BMI and relative psoas cross-sectional area (PCSA) at each level were also evaluated. RESULTS: A-Pr was significantly smaller than A-Ps at L1/2, L2/3 and L3/4 (All p < 0.05); there was no significantly difference of A-Pr between all levels (p = 0.105), but L1/2 seemed to be larger than L3/4, followed by L2/3 and L4/5; A-Pr at each level was not affected by sex (All p > 0.05); linear relationships were found between A-Pr, BMI and PCSA at L1/2 and L3/4. CONCLUSIONS: ROC at L1/2, L2/3 and L3/4 will significantly decrease from supine to right lateral decubitus position and the reason may be due to the relaxed psoas deformation. Using MRI images in supine position for pre-operatively ROC evaluation is not accurate. Spine surgeon should also be more cautious when OLIF is performed at L4/5 where ROC is the smallest. Patients from Asia and those with strong psoas major at L1/2 and L3/4 are also associated with relatively narrow ROC. PMID- 27272495 TI - The utility of PET/CT with (68)Ga-DOTATOC in sarcoidosis: comparison with (67)Ga scintigraphy. AB - OBJECTIVE: This study was designed to compare the clinical efficacy of (68)Ga DOTA-Tyr-octreotide (DOTATOC)-positron emission tomography (PET)/computed tomography (CT) with that of conventional (67)Ga-scintigraphy (GS), and to correlate quantitative parameters on DOTATOC-PET/CT with clinical data, in patients with sarcoidosis. METHODS: Twenty patients who were histologically and/or clinically diagnosed with sarcoidosis and underwent both DOTATOC-PET/CT and GS were analyzed in this study. The numbers of patients with positive findings for each organ were determined. The total numbers of involved nodal areas in the chest, as determined by DOTATOC-PET and gallium single-photon emission tomography (Ga-SPECT), were compared. The correlations between quantitative parameters on PET and clinical laboratory data were evaluated. RESULTS: DOTATOC-PET/CT was positive in 19 patients, being negative in only one patient with chronic inactive sarcoidosis, whereas GS was positive in 17 patients. DOTATOC-PET/CT visualized more lesions in lymph nodes, uvea, and muscles than did Ga-scintigraphy and identified more involved areas than did GS SPECT (p < 0.0001). Whole-body active lesion volume showed a significant, but moderate correlation with angiotensin-converting enzyme level (rho = 0.64, p = 0.0044). CONCLUSIONS: PET/CT with DOTATOC may be superior to conventional GS in detecting sarcoidosis lesions, especially in lymph nodes, uvea, and muscles. Volumetric parameters in DOTATOC-PET/CT may be helpful in estimating the activity of sarcoidosis. PMID- 27272494 TI - The outcome of decompression alone for lumbar spinal stenosis with degenerative spondylolisthesis. AB - PURPOSE: Lumbar spinal stenosis in the presence of degenerative spondylolisthesis is generally treated by means of surgery. The role of lumbar decompression without fusion is not clear. Therefore, the aim of this study was to assess whether patients who undergo decompression alone have a favourable outcome without the need for a subsequent fusion. METHODS: This is a prospective cohort study with single blinding of 83 consecutive patients with lumbar stenosis and degenerative spondylolisthesis treated by decompression, without fusion, using a spinous process osteotomy. Blinded observers collected pre- and post-operative Oswestry Disability Index (ODI), EuroQol Five Dimensions (EQ-5D), and visual analogue scale (VAS) for back and leg pain scores prospectively. Failures for this study were those patients who required a subsequent lumbar fusion procedure at the decompressed levels. Statistical analysis was performed using paired t test and Mann-Whitney test. RESULTS: There were 36 males and 47 females with a mean age of 66 years (range 35-82). The mean follow-up was 36 months (range 19-48 months). The mean pre-operative ODI, EQ-5D, and VAS scores were 52 [standard deviation (SD) 18], 0.25 (SD 0.30), and 61 (SD 22), respectively. All mean scores improved post-operatively to 38 (SD 23), 0.54 (SD 0.34) and 36 (SD 27), respectively. There was a statistically significant improvement in all scores (p <= 0.0001). Nine patients (11 %) required a subsequent fusion procedure and five patients (6 %) required revision decompression surgery alone. CONCLUSION: Our study's results show that a lumbar decompression procedure without arthrodesis in a consecutive cohort of patients with lumbar spinal stenosis with degenerative spondylolisthesis had a significant post-operative improvement in ODI, EQ-5D, and VAS. The rate of post-operative instability and subsequent fusion is not high. Only one in 10 patients in this group ended up needing a subsequent fusion at a mean follow-up of 36 months, indicating that fusion is not always necessary in these patients. PMID- 27272496 TI - A New Temperature Control Shifting Strategy for Enhanced Triterpene Production by Ganoderma lucidum G0119 Based on Submerged Liquid Fermentation. AB - Temperature control is a very important factor on triterpene productivity in submerged liquid fermentation. Temperature effects from 23 to 32 degrees C on triterpene production by Ganoderma lucidum G0119 were investigated in 6-L stirred fermentor. Logistic and Luedeking-Piret equations were used to estimate the mycelial growth and triterpene production kinetics by regression analysis. On that basis, a temperature-shifting fermentation control strategy was established. From 0 to 61 h, culturing was performed at 32 degrees C to get high specific mycelial growth rate. Between 62 and 127 h, the temperature was decreased stepwise from 31 to 30 degrees C to maintain high triterpene productivity. After 128 h, temperature was maintained at 29 degrees C to minimize triterpene production inhibition and sustain high productivity. Elevated triterpene level (0.269 g L-1), yield (0.0101 g g-1), and productivity (0.00207 g (L h)-1) were achieved representing 27.32, 13.94, and 37.11 % higher than submerged liquid fermentation at constant temperature of 29 degrees C, respectively, feasible for the industrial scale. PMID- 27272498 TI - Abomasal ulcers in slaughtered cattle in Austria. AB - OBJECTIVE: In this preliminary study, the prevalence of abomasal ulcers in cattle in Austria was evaluated for the first time. Furthermore, possible management factors contributing to the formation of abomasal ulcers and the diagnostic ability of faecal occult blood tests were evaluated. MATERIAL AND METHODS: Abomasa of 91 calves, 33 cows and 91 bulls were examined for abomasal ulcers after slaughter. The ulcers were recorded, abomasal content pH was measured and faeces were examined for occult blood. The carcass classification was recorded and the owners were presented with a voluntary questionnaire targeted at health-, management- and feeding-practices that could influence gastric health. RESULTS: The median abomasal pH was 3.0 in calves, 3.6 in bulls and 3.9 in cows. More than 50% of all animals had abomasal ulcers, all of which belonged to the slightest kind of lesion. Faecal occult blood tests proved not to be suitable for detecting these ulcers. From the questionnaire no clear tendencies as far as causative factors for abomasal ulcers could be determined. CONCLUSION AND CLINICAL RELEVANCE: It can be assumed that cattle management systems in Austria contribute to the formation of low-grade abomasal ulcers. Due to the lack of a suitable in vivo model to research the formation of abomasal ulcers in cattle all further speculations must remain elusive. Further influencing factors, such as bacterial ulcer colonization, and the true economic and animal welfare impact of these findings need further investigation. The results of this study should be corroborated in a larger, prospective trial. PMID- 27272497 TI - Hepatitis C virus dynamics and cellular gene expression in uPA-SCID chimeric mice with humanized livers during intravenous silibinin monotherapy. AB - Legalon SIL (SIL) is a chemically hydrophilized version of silibinin, an extract of milk thistle (Silybum marianum) seeds that has exhibited hepatoprotective and antiviral effectiveness against hepatitis C virus (HCV) in patients leading to viral clearance in combination with ribavirin. To elucidate the incompletely understood mode of action of SIL against HCV, mathematical modelling of HCV kinetics and human hepatocyte gene expression studies were performed in uPA-SCID chimeric mice with humanized livers. Chronically HCV-infected mice (n = 15) were treated for 14 days with daily intravenous SIL at 469, 265 or 61.5 mg/kg. Serum HCV and human albumin (hAlb) were measured frequently, and liver HCV RNA was analysed at days 3 and 14. Microarray analysis of human hepatocyte gene expression was performed at days 0, 3 and 14 of treatment. While hAlb remained constant, a biphasic viral decline in serum was observed consisting of a rapid 1st phase followed by a second slower phase (or plateau with the two lower SIL dosings). SIL effectiveness in blocking viral production was similar among dosing groups (median epsilon = 77%). However, the rate of HCV-infected hepatocyte decline, delta, was dose-dependent. Intracellular HCV RNA levels correlated (r = 0.66, P = 0.01) with serum HCV RNA. Pathway analysis revealed increased anti inflammatory and antiproliferative gene expression in human hepatocytes in SIL treated mice. The results suggest that SIL could lead to a continuous second phase viral decline, that is potentially viral clearance, in the absence of adaptive immune response along with increased anti-inflammatory and antiproliferative gene expression in human hepatocytes. PMID- 27272499 TI - The nurse response to abnormal vital sign recording in the emergency department. AB - AIMS AND OBJECTIVES: To examine what occurs after a recorded observation of at least one abnormal vital sign in the emergency department. The aims were to determine how often abnormal vital signs were recorded, what interventions were documented, and what factors were associated with documented follow-up for abnormal vital signs. BACKGROUND: Monitoring quality of care, and preventing or intervening before harm occurs to patients are central to nurses' roles. Abnormal vital signs have been associated with poor patient outcomes and require follow-up after the observation of abnormal readings to prevent patient harm related to a deteriorating status. This documentation is important to quality and safety of care. DESIGN: Observational, retrospective chart review. METHODS: Modified Early Warning Score was calculated for all recorded vital signs for 195 charts. Comparisons were made between groups: (1) no abnormal vital signs, (2) abnormal vital sign present, but normal Modified Early Warning Score and (3) critically abnormal Modified Early Warning Score. RESULTS: About 62.1% of charts had an abnormal vital sign documented. Critically abnormal values were present in 14.9%. No documentation was present in 44.6% of abnormal cases. When interventions were documented, it was usually to notify the physician. The timing within the emergency department visit when the abnormalities were observed and the degree of abnormality had significant relationships to the presence of documentation. CONCLUSIONS: It is doubtful that nurses do not recognise abnormalities because more severely abnormal vital signs were more likely to have documented follow-up. Perhaps the interruptive nature of the emergency department or the prioritised actions of the nurse impacted documentation within this study. Further research is required to determine why follow-up is not being documented. RELEVANCE TO CLINICAL PRACTICE: To ensure safety and quality of patient care, accurate documentation of responses to abnormal vital signs is required. PMID- 27272500 TI - Using the cognitive assessment interview to screen cognitive impairment in psychosis. AB - Cognitive impairment in psychosis is closely related to functional outcome, so research into psychotic disorders is focusing most effort on treatments for improving cognition. New treatments must show not only an improvement on neuropsychological tests but also in co-primary measures of cognition. The cognitive assessment interview (CAI) is an interview-based measure of cognition which assesses the impact of cognitive deficits in patients' daily lives. Information obtained from patients and their relatives is integrated into a rater composite score. This study examines the validity of the CAI (adapted to Spanish, CAI-Sp) as a screening instrument for cognitive impairment, compared to an objective test of cognitive functioning. The psychometric properties of the CAI Sp and its association with clinical dimensions are also explored. Eighty-one patients with a psychotic disorder and 38 healthy controls were assessed using the CAI-Sp and the screen for cognitive impairment in psychiatry (SCIP-S). Patients also underwent a clinical assessment. Poorer cognitive functioning as assessed with the CAI-Sp was associated to illness severity, specifically positive, negative and disorganised syndromes. Binary logistic regression showed that the CAI-Sp was able to detect cognitive impairment in patients, when considering CAI-Sp patient and informant information and CAI-Sp rater scores. The CAI-Sp was found to be a valid and reliable scale to assess cognitive functioning in the context of its impact on daily living. Given its ease and speed of application, the CAI-Sp could prove useful in clinical practice, though not a substitute of objective cognitive testing. PMID- 27272501 TI - Do pelvic floor muscle exercises reduce postpartum anal incontinence? A randomised controlled trial. AB - OBJECTIVE: To evaluate the effect of pelvic floor muscle exercises (PFME) for postpartum anal incontinence (AI). DESIGN: A parallel two-armed randomised controlled trial stratified on obstetrical anal sphincter injury with primary sphincter repair and hospital affinity. SETTING: Ano-rectal specialist out patient clinics at two hospitals in Norway. POPULATION: One hundred and nine postpartum women with AI at baseline. METHODS: The intervention group received 6 months of individual physiotherapy-led PFME and the control group written information on PFME. Changes in St. Mark's scores and predictors of post intervention AI were assessed by independent samples t-tests and multiple linear regression analyses, respectively. The study was not blind. MAIN OUTCOME MEASURES: The primary outcome measure was change in AI symptoms on the St. Mark's score from baseline to post-intervention. Secondary outcome measures were manometry measures of anal sphincter length and strength, endoanal ultrasound (EAUS) defect score and voluntary pelvic floor muscle contraction. RESULTS: There was a significant difference in the reduction of St. Mark's scores from baseline to post-intervention in favour of the PFME group (-2.1 versus -0.8 points, P = 0.040). No differences in secondary outcome measures were found between groups. Baseline St. Mark's, PFME group affinity and EAUS defect score predicted post intervention St. Mark's score in the imputed intention-to-treat analyses. The analysis on un-imputed data showed that women performing weekly PFME improved their AI scores more than women in the control group did. CONCLUSIONS: Our results indicate that individually adapted PFME reduces postpartum AI symptoms. TWEETABLE ABSTRACT: Performing regular pelvic floor muscle exercises may be an effective treatment for postpartum anal incontinence. PMID- 27272503 TI - The Putative SLC Transporters Mfsd5 and Mfsd11 Are Abundantly Expressed in the Mouse Brain and Have a Potential Role in Energy Homeostasis. AB - BACKGROUND: Solute carriers (SLCs) are membrane bound transporters responsible for the movement of soluble molecules such as amino acids, ions, nucleotides, neurotransmitters and oligopeptides over cellular membranes. At present, there are 395 SLCs identified in humans, where about 40% are still uncharacterized with unknown expression and/or function(s). Here we have studied two uncharacterized atypical SLCs that belong to the Major Facilitator Superfamily Pfam clan, Major facilitator superfamily domain 5 (MFSD5) and Major facilitator superfamily domain 11 (MFSD11). We provide fundamental information about the histology in mice as well as data supporting their disposition to regulate expression levels to keep the energy homeostasis. RESULTS: In mice subjected to starvation or high-fat diet, the mRNA expression of Mfsd5 was significantly down-regulated (P<0.001) in food regulatory brain areas whereas Mfsd11 was significantly up-regulated in mice subjected to either starvation (P<0.01) or high-fat diet (P<0.001). qRT-PCR analysis on wild type tissues demonstrated that both Mfsd5 and Mfsd11 have a wide central and peripheral mRNA distribution, and immunohistochemistry was utilized to display the abundant protein expression in the mouse embryo and the adult mouse brain. Both proteins are expressed in excitatory and inhibitory neurons, but not in astrocytes. CONCLUSIONS: Mfsd5 and Mfsd11 are both affected by altered energy homeostasis, suggesting plausible involvement in the energy regulation. Moreover, the first histological mapping of MFSD5 and MFSD11 shows ubiquitous expression in the periphery and the central nervous system of mice, where the proteins are expressed in excitatory and inhibitory mouse brain neurons. PMID- 27272502 TI - HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC). AB - PURPOSE: The aim of our study was to evaluate the expression pattern of HER2 overexpression in patients with upper tract urothelial carcinoma (UTUC) and to evaluate its association with clinical outcomes. METHODS: This multicenter retrospective study included 732 patients treated with radical nephroureterectomy for UTUC. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest: Scores of 0 or 1 were considered negative and 2 or 3 as positive. To qualify for 2 scoring, complete membrane staining of more than 10 % of tumor cells at a moderate intensity had to be observed. RESULTS: HER2 was overexpressed in 262 (35.8 %) patients. It was associated with pathologic characteristics such as more advanced T stage (p < 0.001), presence of lymph node metastasis (p = 0.006), high-grade tumor (p < 0.001), tumor necrosis (p = 0.01) and lymphovascular invasion (p = 0.02). Patients with HER2 overexpression had a 1.66-fold increased risk of experiencing disease recurrence (95 % CI 1.24-2.24, p = 0.001), 1.55-fold increased risk of death (95 % CI 1.21-1.99, p = 0.001) and 1.81-fold increased risk of cancer-specific death (95 % CI 1.33-2.48, p < 0.001). On multivariable analysis that adjusted for the effects of standard clinicopathologic variables, HER2 overexpression remained associated with disease recurrence (p = 0.04), overall (p = 0.02) and cancer-specific mortality (p = 0.02). CONCLUSIONS: Approximately, one-third of UTUC patients overexpressed HER2. HER2 overexpression was associated with features of clinically and biologically aggressive disease as well as prognosis. HER2 may represent a good marker for therapeutic risk stratification and potentially a target for therapy in some UTUC tumors. PMID- 27272504 TI - Stromal fibroblasts derived from mammary gland of bovine with mastitis display inflammation-specific changes. AB - Fibroblasts are predominant components of mammary stromal cells and play crucial roles in the development and involution of bovine mammary gland; however, whether these cells contribute to mastitis has not been demonstrated. Thus, we have undertaken biological and molecular characterization of inflammation-associated fibroblasts (INFs) extracted from bovine mammary glands with clinical mastitis and normal fibroblasts (NFs) from slaughtered dairy cows because of fractured legs during lactation. The functional contributions of INFs to normal epithelial cells were also investigated by using an in vitro co-culture model. We present evidence that the INFs were activated fibroblasts and showed inflammation-related features. Moreover, INFs significantly inhibited the proliferation and beta casein secretion of epithelial cells, as well as upregulated the expression of tumor necrosis factor-alpha and interleukin-8 in epithelial cells. These findings indicate that functional alterations can occur in stromal fibroblasts within the bovine mammary gland during mastitis, demonstrating the importance of stromal fibroblasts in bovine mastitis and its treatment. PMID- 27272505 TI - Plant-Derived Polyphenols Interact with Staphylococcal Enterotoxin A and Inhibit Toxin Activity. AB - This study was performed to investigate the inhibitory effects of 16 different plant-derived polyphenols on the toxicity of staphylococcal enterotoxin A (SEA). Plant-derived polyphenols were incubated with the cultured Staphylococcus aureus C-29 to investigate the effects of these samples on SEA produced from C-29 using Western blot analysis. Twelve polyphenols (0.1-0.5 mg/mL) inhibited the interaction between the anti-SEA antibody and SEA. We examined whether the polyphenols could directly interact with SEA after incubation of these test samples with SEA. As a result, 8 polyphenols (0.25 mg/mL) significantly decreased SEA protein levels. In addition, the polyphenols that interacted with SEA inactivated the toxin activity of splenocyte proliferation induced by SEA. Polyphenols that exerted inhibitory effects on SEA toxic activity had a tendency to interact with SEA. In particular, polyphenol compounds with 1 or 2 hexahydroxydiphenoyl groups and/or a galloyl group, such as eugeniin, castalagin, punicalagin, pedunculagin, corilagin and geraniin, strongly interacted with SEA and inhibited toxin activity at a low concentration. These polyphenols may be used to prevent S. aureus infection and staphylococcal food poisoning. PMID- 27272507 TI - Reply for the Letter to the Editor for the Manuscript "Sleeve Gastrectomy and Roux-y-Gastric Bypass Lead to Comparable Changes in Body Composition After Adjustment for Initial Body Mass Index". PMID- 27272506 TI - TSH Normalization in Bariatric Surgery Patients After the Switch from L-Thyroxine in Tablet to an Oral Liquid Formulation. AB - OBJECTIVE: Drug malabsorption is one of the potential troubles after bariatric surgery. Evidence for diminished levothyroxine (L-T4) absorption has been reported in patients after bariatric surgery. METHODS: This study reports 17 cases of hypothyroid patients [who were well replaced with thyroxine tablets (for >1 year) to euthyroid thyrotropin (TSH) levels before surgery (13 Roux-en-Y gastric bypasses (RYGB); 4 biliary pancreatic diversions (BPD))]. From 3 to 8 months after surgery, these patients had elevated TSH levels. Patients were then switched from oral tablets to a liquid L-T4 formulation (with the same dosage, 30 min before breakfast). RESULTS: Two-three months after the switch, TSH was significantly reduced both in patients treated with RYGB, as in those treated with BPD, while FT4 and FT3 levels were not significantly changed (RYGB group, TSH MUIU/mL: 7.58 +/- 3.07 vs 3.808 +/- 1.83, P < 0.001; BPD group, TSH MUIU/mL: 8.82 +/- 2.76 vs 3.12 +/- 1.33, P < 0.01). CONCLUSIONS: These results first show that liquid L-T4 could prevent the problem of malabsorption in patients with BPD and confirm those of previous studies in patients submitted to RYGB, suggesting that the L-T4 oral liquid formulation could circumvent malabsorption after bariatric surgery. PMID- 27272509 TI - A single center's conversion from roller pump to centrifugal pump technology in extracorporeal membrane oxygenation. AB - OVERVIEW: Recent advances in blood pump technology have led to an increased use of centrifugal pumps for prolonged extracorporeal membrane oxygenation (ECMO). Data from the Extracorporeal Life Support Organization confirms that many institutions have converted to centrifugal pumps after prior experience with roller pump technology. Centrifugal pump technology is more compact and may generate less heat and hemolysis than a conventional roller pump. Based on the potential advantages of centrifugal pumps, a decision was made institution-wide to convert to centrifugal pump technology in pediatric implementation of ECMO. Based on limited prior experience with centrifugal pumps, a multidisciplinary approach was used to implement this new technology. The new centrifugal pump (Sorin Revolution, Arvada, CO) was intended for ECMO support in the cardiac intensive care unit (CICU), the pediatric intensive care unit (PICU) and the neonatal intensive care unit (NICU). DESCRIPTION: The perfusion team used their knowledge and expertise with centrifugal pumps to create the necessary teaching tools and interactive training sessions for the technical specialists who consisted primarily of registered nurses and respiratory therapists. The first phase consisted of educating all personnel involved in the care of the ECMO patient, followed by patient implementation in the CICU, followed by the PICU and NICU. CONCLUSION: The institution-wide conversion took several months to complete and was well received among all disciplines in the CICU and PICU. The NICU personnel did use the centrifugal pump circuit, but decided to revert back to using the roller pump technology. A systematic transition from roller pump to centrifugal pump technology with a multidisciplinary team can ensure a safe and successful implementation. PMID- 27272508 TI - Nutrient Control of Yeast Gametogenesis Is Mediated by TORC1, PKA and Energy Availability. AB - Cell fate choices are tightly controlled by the interplay between intrinsic and extrinsic signals, and gene regulatory networks. In Saccharomyces cerevisiae, the decision to enter into gametogenesis or sporulation is dictated by mating type and nutrient availability. These signals regulate the expression of the master regulator of gametogenesis, IME1. Here we describe how nutrients control IME1 expression. We find that protein kinase A (PKA) and target of rapamycin complex I (TORC1) signalling mediate nutrient regulation of IME1 expression. Inhibiting both pathways is sufficient to induce IME1 expression and complete sporulation in nutrient-rich conditions. Our ability to induce sporulation under nutrient rich conditions allowed us to show that respiration and fermentation are interchangeable energy sources for IME1 transcription. Furthermore, we find that TORC1 can both promote and inhibit gametogenesis. Down-regulation of TORC1 is required to activate IME1. However, complete inactivation of TORC1 inhibits IME1 induction, indicating that an intermediate level of TORC1 signalling is required for entry into sporulation. Finally, we show that the transcriptional repressor Tup1 binds and represses the IME1 promoter when nutrients are ample, but is released from the IME1 promoter when both PKA and TORC1 are inhibited. Collectively our data demonstrate that nutrient control of entry into sporulation is mediated by a combination of energy availability, TORC1 and PKA activities that converge on the IME1 promoter. PMID- 27272510 TI - Parallel linear dynamic models can mimic the McGurk effect in clinical populations. AB - One of the most common examples of audiovisual speech integration is the McGurk effect. As an example, an auditory syllable /ba/ recorded over incongruent lip movements that produce "ga" typically causes listeners to hear "da". This report hypothesizes reasons why certain clinical and listeners who are hard of hearing might be more susceptible to visual influence. Conversely, we also examine why other listeners appear less susceptible to the McGurk effect (i.e., they report hearing just the auditory stimulus without being influenced by the visual). Such explanations are accompanied by a mechanistic explanation of integration phenomena including visual inhibition of auditory information, or slower rate of accumulation of inputs. First, simulations of a linear dynamic parallel interactive model were instantiated using inhibition and facilitation to examine potential mechanisms underlying integration. In a second set of simulations, we systematically manipulated the inhibition parameter values to model data obtained from listeners with autism spectrum disorder. In summary, we argue that cross modal inhibition parameter values explain individual variability in McGurk perceptibility. Nonetheless, different mechanisms should continue to be explored in an effort to better understand current data patterns in the audiovisual integration literature. PMID- 27272511 TI - Glutathione protects Candida albicans against horseradish volatile oil. AB - Horseradish essential oil (HREO; a natural mixture of different isothiocyanates) had strong fungicide effect against Candida albicans both in volatile and liquid phase. In liquid phase this antifungal effect was more significant than those of its main components allyl, and 2-phenylethyl isothiocyanate. HREO, at sublethal concentration, induced oxidative stress which was characterized with elevated superoxide content and up-regulated specific glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase activities. Induction of specific glutathione S-transferase activities as marker of glutathione (GSH) dependent detoxification was also observed. At higher concentration, HREO depleted the GSH pool, increased heavily the superoxide production and killed the cells rapidly. HREO and the GSH pool depleting agent, 1-chlore-2,4-dinitrobenzene showed strong synergism when they were applied together to kill C. albicans cells. Based on all these, we assume that GSH metabolism protects fungi against isothiocyanates. PMID- 27272512 TI - Sequential dependencies in categorical judgments of radiographic images. AB - Sequential context effects, the psychological interactions occurring between the events of successive trials when a sequence of similar stimuli are judged, have interested psychologists for decades. It has been well established that individuals exhibit sequential context effects in psychophysical experiments involving unidimensional stimuli. Recent evidence shows that these effects generalize to quantitative judgments of more complex multidimensional stimuli such as images of faces, chairs, and shoes. In this article, we test for the presence of sequential context effects by re-examining previously published data on categorical judgments of 234 complex radiographic images made by 20 experienced physicians and 20 medical students engaged in an online training task. We found that medical students, but not experienced physicians, displayed evidence of sequential context effects. We also found evidence suggesting that as the students learned over blocks of trials, they tended to shift from relative comparisons between consecutive images toward more independent comparisons of each image against (strengthening) internalized standards. PMID- 27272513 TI - Applying positioning theory to examine interactions between simulated patients and medical students: a narrative analysis. AB - In their journey to becoming doctors, students engage with a range of teachers and trainers. Among these are simulated patients (SPs), who, through role playing, assist students to develop their communication and physical examination skills, in contexts of formative and summative assessments. This paper explores the teaching and learning relationship between medical students and SPs, and considers how this might affect feedback and assessment. 14 SPs were interviewed on the subject of medical students' professional identity development in 2014. Data were examined using narrative analysis in conjunction with positioning theory to identify the positions that SPs assigned to themselves and to students. Narrative analysis yielded three interpretative positioning themes: Occupational, familial and cultural and discursive and embodied positioning. The interview process revealed that SPs adopt different positions intra-and interpersonally. SPs appear to hold dissonant perceptions of students in terms relating to their emerging professional identities, which may confound assessment and feedback. Training should include reflections on the SP/student relationship to uncover potential biases and positions, giving SPs the opportunity to reflect on and manage their individual and occupational selves. PMID- 27272514 TI - [Malignant hyperthermia syndrome in the intensive care unit : Differential diagnosis and acute measures]. AB - Malignant hyperthermia is a life-threatening disease caused by derangement of the autonomic nerve system and hypermetabolism of the peripheral musculature. Commonly body core temperatures of more than 40 degrees C will be found in this disease which is caused mostly by psychopharmacological drugs like antidepressants, neuroleptics but also antibiotics, pain killers, anti-Parkinson drugs, and volatile anesthetics. The inducers of malignant hyperthermia interact with postsynaptic receptors (serotonin, anticholinergics) or muscular intracellular structures responsible for calcium utilization (volatile anesthetics, succinylcholine). Rarely malignant hyperthermia is a consequence of mental stress or vigorous exercise and or heat. Malignant hyperthermic syndromes lead to a severe dysbalance of the autonomic nerve system accompanied by rhabdomyolysis, disseminated intravascular coagulopathy, and finally multi-organ failure. Accordingly, medical management is primarily directed to stabilize vital functions, withdrawal of the causing drug, and if possible antagonizing toxic substances. The leading symptom hyperthermia needs to be treated physically with available cooling systems. PMID- 27272515 TI - Quality of Life, Stigma and Burden Perception Among Family Caregivers and Patients with Psychiatric Illnesses in Jordan. AB - The literature reported several factors which could impact the quality of life of caregivers and patients with psychiatric illnesses. This study aimed to determine the level of quality of life among a sample of 532 of caregivers and patients with psychiatric illness at two out-patient mental health clinics in Northern Jordan, and to examine the relationships of sociodemographic characteristics, stigma and caregiver perceptions of burden with quality of life. A correlational descriptive design was utilized. Three self-administered questionnaires were used. Results indicated that patients had low to moderate QOL, and they suffered moderate to high stigma. Also, family caregivers perceived low to moderate QOL. Patients' and family caregivers' stigma perception correlated negatively and significantly with WHOQOL-BREF. Family caregivers' burden correlated negatively and significantly with all domains of WHOQOL-BREF, total QOL-100, and self reported general health. Health care providers should assure the importance of focusing more toward minimizing stigma and promoting physical and general health to maintain a good quality of life of caregivers and patients with mental illnesses. PMID- 27272516 TI - For Better or Worse: Friendship Choices and Peer Victimization Among Ethnically Diverse Youth in the First Year of Middle School. AB - As children approach early adolescence, the risk of peer victimization often increases. Many children experience some form of peer victimization during this time, but children who experience chronic victimization may be particularly vulnerable to adjustment difficulties. Thus, identifying risk and protective factors associated with chronic victimization continues to be an important area of research. This study examined the effect of change in the victimization of friends on change in children's own victimization, taking into account the ethnic group representation of children in their classes. Over 3000 6th grade students (52 % female; M = 11.33 years) were drawn from 19 middle schools varying in ethnic composition. Friendships were distinguished by type-reciprocal, desired, and undesired-and a novel methodology for measuring ethnic group representation at the individual level was employed. Multilevel modeling indicated that change in friends' victimization from fall to spring of 6th grade had a differential impact on children's own victimization by friendship type and that the benefits and consequences of change in friends' victimization were especially pronounced for children in the numerical ethnic majority. The findings underscore the role of friendship choices in peer victimization, even if those choices are not reciprocated, and highlight the unique social risks associated with being in the numerical ethnic majority. PMID- 27272517 TI - Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: a randomized double-blind controlled study. AB - The aim of this study was to verify if low-level laser therapy could be useful to reduce chemotherapy-related oral mucositis grading and pain in childhood undergoing chemotherapy. A randomized double-blind clinical trial was carried out. Patients from 3 to 18 years of age undergoing cancer therapy and presenting OM grade 2 or more were eligible for this study. Patients were randomly divided in two groups: group A received laser therapy from the day of OM diagnosis and other 3 consecutive days (830 nm wavelength, power 150 mW, spot size 1 cm(2), 30 s per cm(2), energy density 4.5 J/cm(2)); group B received sham therapy (placebo) with the same timing. Two blind clinicians performed OM scoring and pain evaluation at day 1 (immediately before the beginning of laser treatment-T0), day 4 (after finishing laser therapy cycle-T1) and at day 7 (T2) as follow-up. A total of 123 patients were included in the study. Group A was composed of 62 children while group B is 61; in both groups, there was a progressive reduction in grade of OM, and at day 7, not every mucosal lesion disappeared. The difference in the decline of OM grading between the two groups resulted not statistically significant (p = 0.07). A statistically significant difference in pain reduction between two groups both at T1 and at T2 (p < 0.005) was observed. This study demonstrated the efficacy of LLLT in reducing pain due to chemotherapy induced oral mucositis in children, while no significant benefit was noted in reducing OM grade. PMID- 27272519 TI - Temporal Variation of Wood Density and Carbon in Two Elevational Sites of Pinus cooperi in Relation to Climate Response in Northern Mexico. AB - Forest ecosystems play an important role in the global carbon cycle. Therefore, understanding the dynamics of carbon uptake in forest ecosystems is much needed. Pinus cooperi is a widely distributed species in the Sierra Madre Occidental in northern Mexico and future climatic variations could impact these ecosystems. Here, we analyze the variations of trunk carbon in two populations of P. cooperi situated at different elevational gradients, combining dendrochronological techniques and allometry. Carbon sequestration (50% biomass) was estimated from a specific allometric equation for this species based on: (i) variation of intra annual wood density and (ii) diameter reconstruction. The results show that the population at a higher elevation had greater wood density, basal area, and hence, carbon accumulation. This finding can be explained by an ecological response of trees to adverse weather conditions, which would cause a change in the cellular structure affecting the within-ring wood density profile. The influence of variations in climate on the maximum density of chronologies showed a positive correlation with precipitation and the Multivariate El Nino Southern Oscillation Index during the winter season, and a negative correlation with maximum temperature during the spring season. Monitoring previous conditions to growth is crucial due to the increased vulnerability to extreme climatic variations on higher elevational sites. We concluded that temporal variability of wood density contributes to a better understanding of environmental historical changes and forest carbon dynamics in Northern Mexico, representing a significant improvement over previous studies on carbon sequestration. Assuming a uniform density according to tree age is incorrect, so this method can be used for environmental mitigation strategies, such as for managing P. cooperi, a dominant species of great ecological amplitude and widely used in forest industries. PMID- 27272518 TI - Effect of pre-exercise phototherapy applied with different cluster probe sizes on elbow flexor muscle fatigue. AB - Phototherapy has been used for reducing muscle fatigue. In view of the various types of phototherapy cluster probes available in the market, the purpose of this study was to compare the effects of a similar phototherapy dosage with two different cluster probes on elbow flexor muscle fatigue: small cluster probe (SC = 9 diodes; 7.5 cm(2)) vs. large cluster probe (LC = 33 diodes; 30.2 cm(2)). Ten physically active male aged 18-35 years participate in a randomized, crossover, double-blind, placebo-controlled trial, which each participant was submitted to the same testing protocol in four sessions (separated by at least 48 h) with different treatments: LC-phototherapy, SC-phototherapy, LC-placebo, and SC placebo. The elbow flexion maximal isometric voluntary contraction (MIVC) was performed before and after a fatigue protocol (60 % of MIVC until exhaustion). Electromyography (EMG) of the biceps brachii muscle was collected during all testing procedure. Phototherapy with dose of 60 J per muscle [LC: 33 diodes = 5 lasers (850 nm), 12 LEDs (670 nm), 8 LEDs (880 nm), and 8 LEDs (950 nm); SC: 9 diodes = 5 lasers (850 nm) and 4 LEDs (670 nm)] or placebo applications occurred before fatigue protocol. Two-way ANOVA (treatment and time factors) and one-way ANOVA were used, followed by LSD post hoc. Time to exhaustion was significantly higher in active LC (15 %; p = 0.031) and SC (14 %; p = 0.038) in comparison with their respective placebo treatments, without differences between LC and SC (p > 0.05) or between placebo conditions (p > 0.05). This larger exercise tolerance in phototherapy conditions was not accompanied by a higher decrement in the volunteers' maximal strength capacity (11-15 %; p > 0.05 for all). EMG signals presented no difference between the four condition tested here. In both large and small cluster probes (according parameters tested in this study) led to reduced fatigue in elbow flexor muscles, without difference between them. PMID- 27272521 TI - CRISPR/Cas9: a breakthrough in generating mouse models for endocrinologists. AB - CRISPR/Cas9 is a recent development in genome editing which is becoming an indispensable element of the genetic toolbox in mice. It provides outstanding possibilities for targeted modification of the genome, and is often extremely efficient. There are currently two main limitations to in ovo genome editing in mice: the first is mosaicism, which is frequent in founder mice. The second is the difficulty to evaluate the advent of off-target mutations, which often imposes to wait for germline transmission to ensure genetic segregation between wanted and unwanted genetic mutations. However rapid progresses are made, suggesting that these difficulties can be overcome in the near future. PMID- 27272520 TI - Reversal of fortune: estrogen receptor-beta in endometriosis. AB - Enhanced inflammation and reduced apoptosis sustain the growth of endometriotic lesions. Alterations in the expression of estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) accompany the conversion of resident endometrial cells within the normal uterine environment to ectopic lesions located in extrauterine sites. Recent studies highlighted in this focused review linked ERbeta to dysregulation of apoptotic and inflammatory networks involving novel interacting partners in endometriosis. The elucidation of these nongenomic actions of ERbeta using human cells and mouse models is an important step in understanding key regulatory pathways that are disrupted leading to disease establishment and progression. PMID- 27272522 TI - Reproductive Effects of Two Polybrominated Diphenyl Ethers on the Rotifer Brachionus plicatilis. AB - The effects of two polybrominated diphenyl ethers (PBDEs) on the reproduction of the rotifer Brachionus plicatilis were investigated. Results showed that sexual maturation was promoted by tetra-brominated diphenyl ether-47 (BDE-47) and deca brominated diphenyl ether-209 (BDE-209), whereas fecundity was inhibited by BDE 47, but promoted by BDE-209. Additionally, both PBDEs affected the expression of two genes, vasa and nanos mRNA, related to rotifer reproduction. This suggests a possible regulatory molecular mechanism at the transcriptional level. Our research extends the current knowledge of the ecotoxicological mechanism induced by PBDEs and provides further essential information for assessing the risks of PBDE contamination in marine ecosystems. PMID- 27272524 TI - Misdemeanor Arrestees With Mental Health Needs: Diversion and Outpatient Services as a Recidivism Reduction Strategy. AB - Individuals with mental illnesses who are arrested for criminal activity cycle between criminal justice and mental health systems at disproportionately high rates. Studying recidivism of this population has been difficult due to separate system data bases. This study compared recidivism outcomes of 102 adults with mental illness who were arrested for a misdemeanor offense. One group had a diagnosed mental illness ( n = 58) and the other group was diagnosed with co occurring mental health and substance abuse disorders ( n = 44). As a condition of their personal recognizance bond, both groups voluntarily agreed to stabilize on medication and report to community-based outpatient mental health clinic. Participants in both groups had fewer rearrests and fewer days in jail in the 12 months following discharge from diversion relative to the 12 months prior to diversion participation. Outpatient mental health service utilization following 24 hr in jail seems to be a viable means of reducing recidivism among accused misdemeanant defendants. PMID- 27272525 TI - Come and Knock on Our Door: Offenders' Perspectives on Home Visits Through Ecological Theory. AB - The use of home visits has a long and storied history in the United States from different disciplines, such as nursing, prenatal mothers, young families, health promotion, and community corrections. Ecological theory explains how formal actors play a role in the promotion in the health field through home visits, but does not address community corrections home visits. Through the use of 30 semi structured interviews, this research seeks to expand the understanding of ecological theory by capturing the perceptions of offenders sentenced to home visits conducted by a sheriff's office. The findings suggest the participants supported the home visits by formal agents and, in general, the home visits created an atmosphere of respect between the participants and sheriff's office personnel. This study creates the context for future research to understand the role of formal agents in recidivism and evaluate the efficacy of home visits by community corrections agencies. PMID- 27272523 TI - Intron Derived Size Polymorphism in the Mitochondrial Genomes of Closely Related Chrysoporthe Species. AB - In this study, the complete mitochondrial (mt) genomes of Chrysoporthe austroafricana (190,834 bp), C. cubensis (89,084 bp) and C. deuterocubensis (124,412 bp) were determined. Additionally, the mitochondrial genome of another member of the Cryphonectriaceae, namely Cryphonectria parasitica (158,902 bp), was retrieved and annotated for comparative purposes. These genomes showed high levels of synteny, especially in regions including genes involved in oxidative phosphorylation and electron transfer, unique open reading frames (uORFs), ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs), as well as intron positions. Comparative analyses revealed signatures of duplication events, intron number and length variation, and varying intronic ORFs which highlighted the genetic diversity of mt genomes among the Cryphonectriaceae. These mt genomes showed remarkable size polymorphism. The size polymorphism in the mt genomes of these closely related Chrysoporthe species was attributed to the varying number and length of introns, coding sequences and to a lesser extent, intergenic sequences. Compared to publicly available fungal mt genomes, the C. austroafricana mt genome is the second largest in the Ascomycetes thus far. PMID- 27272526 TI - Evaluating Restorative Justice Circles of Support and Accountability: Can Social Support Overcome Structural Barriers? AB - In a climate in which stigmatic shaming is increasing for sex offenders as they leave prison, restorative justice practices have emerged as a promising approach to sex offender reentry success and have been shown to reduce recidivism. Criminologists and restorative justice advocates believe that providing ex offenders with social support that they may not otherwise have is crucial to reducing recidivism. This case study describes the expressive and instrumental social support required and received, and its relationship to key outcomes, by sex offenders who participated in Circles of Support and Accountability (COSAs), a restorative justice, reentry program in Minnesota. In-depth interviews with re entering sex offenders and program volunteers revealed that 75% of offenders reported weak to moderate levels of social support leaving prison, 70% reported receiving instrumental support in COSAs, and 100% reported receiving expressive support. Findings inform work on social support, structural barriers, and restorative justice programming during sex offender reentry. PMID- 27272527 TI - Improving Type 2 Diabetes Patient Health Outcomes with Individualized Continuing Medical Education for Primary Care. AB - INTRODUCTION: This study provided physicians with continuing medical education (CME) related to type 2 diabetes and evaluated the effect on patient health outcomes. METHODS: Physicians participated in multi-platform CME (live and online programs) and completed a 25 item questionnaire for patient baseline (3-months pre-CME activity) and follow-up visits (>=6-months post-CME activity). Changes in physician knowledge and patient health outcomes were evaluated. RESULTS: 34 physicians completed both phases of the CME curricula and submitted data for 264 patients. Significant improvements were observed in physician knowledge after the live (p < 0.05) and online programs (p < 0.0005). Mean patient glycated hemoglobin (HbA1c) absolute reduction of 1.15% (p < 0.0001) was reported. CONCLUSIONS: CME is an effective tool to close established practice gaps and potentially help improve patient health outcomes. PMID- 27272528 TI - Psychometric Testing of the Defense and Veterans Pain Rating Scale (DVPRS): A New Pain Scale for Military Population. AB - OBJECTIVE: The Defense and Veterans Pain Rating Scale (DVPRS 2.0) is a pain assessment tool that utilizes a numerical rating scale enhanced by functional word descriptors, color coding, and pictorial facial expressions matched to pain levels. Four supplemental questions measure how much pain interferes with usual activity and sleep, and affects mood and contributes to stress. METHODS: Psychometric testing was performed on a revised DVPRS 2.0 using data from 307 active duty service members and Veterans experiencing acute or chronic pain. A new set of facial representations designating pain levels was tested. RESULTS: Results demonstrated acceptable internal consistency reliability (Cronbach's alpha = 0.871) and test-retest reliability (r = 0.637 to r = 0.774) for the five items. Excellent interrater agreement was established for correctly ordering faces depicting pain levels and aligning them on the pain intensity scale (Kendall's coefficient of concordance, W = 0.95 and 0.959, respectively). Construct validity was supported by an exploratory principal component factor analysis and known groups validity testing. Most participants, 70.9%, felt that the DVPRS was superior to other pain rating scales. CONSCLUSION: The DVPRS 2.0 is a reliable and valid instrument that provides standard language and metrics to communicate pain and related outcomes. PMID- 27272530 TI - HIV infection and bone disease. AB - The success of antiretroviral therapy in treating HIV infection has greatly prolonged life expectancy in affected individuals, transforming the disease into a chronic condition. A number of HIV-associated non-AIDS comorbidities have emerged in the ageing HIV-infected population, including osteoporosis and increased risk of fracture. The pathogenesis of fracture is multifactorial with contributions from both traditional and HIV-specific risk factors. Significant bone loss occurs on initiation of antiretroviral therapy but stabilizes on long term therapy. Fracture risk assessment should be performed in HIV-infected individuals and bone mineral density measured when indicated. Lifestyle measures to optimize bone health should be advised and, in individuals at high risk of fracture, treatment with bisphosphonates considered. PMID- 27272531 TI - The Holy Grail of prevention of sexually transmitted infections in travellers. PMID- 27272532 TI - Sexual behaviour of backpackers who visit Koh Tao and Koh Phangan, Thailand: a cross-sectional study. AB - OBJECTIVES: To measure the proportion of backpackers engaging in unprotected sex while travelling in Thailand and to identify predictors of unsafe sexual behaviour. METHODS: A cross-sectional study using an anonymous questionnaire was performed. English-speaking backpackers, excluding US and Thai citizens, were recruited while travelling through the piers of Koh Tao and Koh Phangan between 25 January and 13 March 2013. RESULTS: 61.5% (1238/2013) respondents were travelling without a long-term sexual partner, of whom 39.1% (29.4% females; 51.9% males) reported intercourse with a new partner. 36.8% of these reported inconsistent/no condom use. Inconsistent condom use was independently associated with age <25 years, UK (vs Canadian) nationality and not bringing condoms from home. Backpackers who brought condoms from home were more likely to have sex with a new partner. Male gender and longer trip length increased the likelihood of new partner acquisition and overall risk of unsafe sex but were not associated with inconsistent condom use. New partners were most commonly backpackers from other countries. Men were more likely than women to have sex with a local person. CONCLUSIONS: Backpackers visiting Thailand frequently report unsafe sex. Partner demographics demonstrate a mechanism of international sexually transmitted infection (STI) transfer. In an era of growing antibiotic resistance and continuing HIV transmission, targeting unsafe sex in backpackers has the potential to reduce STI incidence internationally. These data highlight the need for innovative public health intervention. To focus such measures, future research may elucidate why certain groups are at higher risk. PMID- 27272533 TI - Forming new sex partnerships while overseas: findings from the third British National Survey of Sexual Attitudes & Lifestyles (Natsal-3). AB - OBJECTIVES: Travelling away from home presents opportunities for new sexual partnerships, which may be associated with sexually transmitted infection (STI) risk. We examined the prevalence of, and factors associated with, reporting new sexual partner(s) while overseas, and whether this differed by partners' region of residence. METHODS: We analysed data from 12 530 men and women aged 16-74 years reporting >=1 sexual partner(s) in the past 5 years in Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a probability survey undertaken 2010-2012. RESULTS: 9.2% (95% CI 8.3% to 10.1%) of men and 5.3% (4.8% to 5.8%) of women reported new sexual partner(s) while overseas in the past 5 years. This was strongly associated with higher partner numbers and other sexual and health risk behaviours. Among those with new partners while overseas, 72% of men and 58% of women reported partner(s) who were not UK residents. Compared with those having only UK partners while abroad, these people were more likely to identify as 'White Other' or 'Non-White' (vs White British ethnicity), report higher partner numbers, new partners from outside the UK while in the UK and paying for sex (men only) all in the past 5 years. There was no difference in reporting STI diagnosis/es during this time period. CONCLUSIONS: Reporting new partners while overseas was associated with a range of sexual risk behaviours. Advice on sexual health should be included as part of holistic health advice for all travellers, regardless of age, destination or reason for travel. PMID- 27272534 TI - Trace Elements in Sea Ducks of the Alaskan Arctic Coast: Patterns of Variation Among Species, Sexes, and Ages. AB - Climate change and increasing industrialization in the Arctic call for the collection of reference data for assessing changes in contaminant levels. For migratory birds, measuring and interpreting changes in trace element burdens on Arctic breeding areas require insights into factors such as sex, body size, or wintering area that may modify patterns independently of local exposure. In the Alaskan Arctic, we determined levels of trace elements in liver and kidney of common eiders (Somateria mollissima) and long-tailed ducks (Clangula hyemalis) from the Prudhoe Bay oil field and of king eiders (S. spectabilis) and threatened spectacled eiders (S. fischeri) and Steller's eiders (Polystica stelleri) from near the town of Barrow. Small-bodied Steller's eiders and long-tailed ducks from different locations had similarly low levels of selenium (Se), cadmium (Cd), and copper (Cu), perhaps reflecting high mass-specific rates of metabolic depuration during long spring migrations through areas of low exposure. In larger species, Se, Cd, and Cu concentrations were higher in adults than juveniles suggesting that these elements were acquired in nonbreeding marine habitats. Adult male spectacled eiders had exceptionally high Se, Cd, and Cu compared with adult females, possibly because of depuration into eggs and longer female occupancy of nonmarine habitats. Adult female common eiders and juvenile long-tailed ducks at Prudhoe Bay had high and variable levels of Pb, potentially due to local exposure. Explanations for substantial variations in Hg levels were not apparent. Further research into reasons for differing element levels among species and sexes will help clarify the sources, pathways, and risks of exposure. PMID- 27272535 TI - Temporal Variations of O3 and NO x in the Urban Background Atmosphere of Nanjing, East China. AB - Rapid economic growth has given rise to a significant increase in ozone (O3) precursor emissions in many regions of China. An improved understanding of O3 formation in response to different precursor emissions is imperative to address the highly nonlinear O3 problem and to provide a solid scientific basis for efficient O3 abatement in these regions. To this end, this study was performed in Nanjing using a set of observational data from June 1, 2013, to May 31, 2014. The results showed that O3 concentrations were positively correlated with wind speed and temperature and were significantly negatively correlated with relative humidity. The highest monthly daytime, nighttime, and daily average O3 concentrations were observed in summer with values of approximately 46, 18 and 30 ppb, respectively. The lowest O3 concentrations were observed in November through January with values as low as 17, 4, and 9 ppb for the daytime, nighttime, and daily concentrations, respectively. The highest daytime average NO and NO2 concentrations were observed in December, whereas the lowest concentrations were observed in July. A unimodal O3 peak was observed with the highest O3 levels in summer followed by spring and then autumn; the lowest levels observed in the winter. The O3 concentration reached maximum levels at 14:00 to 15:00 h (local standard time). It was found that the crossover occurred with approximately several hours difference with the earliest occurring in summer (06:00 h) followed by spring (08:00 h), autumn (09:00 h), and winter (10:30 h). Furthermore, the highest constant rate of O3 accumulation was observed in summer (5.6 ppb/h) followed by autumn (4.8 ppb/h), spring (4.5 ppb/h), and winter (2.7 ppb/h). The oxidant intercept ranged from 28.4 ppb in January to 58.6 ppb in June, although the slope also shows substantial variation from 0.18 in June to 0.67 in August. The weekend effect is stronger in spring and summer than in autumn and winter and is more intense on Sundays than on Saturdays. Thus, the decrease of O3 levels during weekends suggests that it may be NO x -sensitive. PMID- 27272536 TI - Effect of sociodemographic factors on survival of people living with HIV. AB - PURPOSE OF REVIEW: The purpose is to describe and understand the sociodemographic determinants of survival in people living with HIV within high-income countries in the context of the current recommendation of universal antiretroviral therapy for all HIV-infected persons, irrespective of their CD4 cell count. RECENT FINDINGS: Survival rates in people living with HIV have experienced remarkable increases in the last decade because of more efficacious and well tolerated treatments. Still, these improvements are unevenly distributed between regions across the world as well as within regions. HIV outcomes are heavily influenced by what are known as the 'social determinants' of health which have traditionally encompassed the gender, race/ethnicity, and socioeconomic axes. The evidence that these social determinants are now more important than before (more and earlier interventions are now available), has become stronger in the last 2 years. SUMMARY: Because antiretroviral therapy is now recommended for all HIV-infected persons, sociodemographic factors limiting access to testing, treatment, and retention in care will undoubtedly jeopardize the UNAIDS aspirational objective to end AIDS by 2030. Innovative interventions targeting individuals with social vulnerability are urgently needed to ensure that social inequalities do not continue to be linked with higher mortality. PMID- 27272537 TI - Interventions to improve treatment, retention and survival outcomes for adolescents with perinatal HIV-1 transitioning to adult care: moving on up. AB - PURPOSE OF REVIEW: There is an increasing number of deaths among adult survivors of perinatal HIV. Multiple and complex factors drive this mortality, including problems with retention in care and adherence during adolescence, coupled with the critical period of transition from paediatric to adult care, increasing their risk of treatment failure and severe immunosuppression. We reviewed studies that evaluated the impact of service delivery interventions to improve the health of perinatally infected adolescents living with HIV (P-ALHIV) to gain insight into what might help them survive the vulnerable period of adolescence. RECENT FINDINGS: Youth-focused health services and individual-level interventions may improve P-ALHIV adherence and retention in care. However, there have been few studies, many with small sample sizes and with short durations of follow-up that end before the transition period. Studies from other childhood-onset chronic diseases are similarly limited. SUMMARY: Further studies are urgently needed to identify optimal intervention strategies to reduce mortality and poor outcomes as the adolescent population expands and ages into adult care. Until we have a more robust evidence base, programmes can develop transition plans based on best practice recommendations to optimize the health and longevity of ALHIV in adulthood. PMID- 27272538 TI - Cognitive stimulation therapy in the Italian context: its efficacy in cognitive and non-cognitive measures in older adults with dementia. AB - OBJECTIVE: Cognitive stimulation therapy (CST) has been shown to have significant benefits in enhancing cognitive functioning and improving the quality of life of people with mild to moderate dementia. The present study examines the efficacy of the Italian version of the therapy (CST-IT). METHODS: Older adults with mild to moderate dementia (n = 39) were randomly assigned to two programs: one group participated in the CST-IT, consisting of 14 sessions (twice a week for 7 weeks) and the active control group took part in alternative general activities. The outcome measures were cognitive functioning (measured by the Mini-Mental State Examination-MMSE-, the Alzheimer's Disease Assessment scale-cognitive subscale, the backward digit span test, and a narrative language test); quality of life (Quality of life--Alzheimer's Disease scale); mood (Cornell scale for depression in dementia and the social and emotional loneliness scale); functional activities in daily living (Disability Assessment for Dementia); and behavior (neuropsychiatric inventory). RESULTS: After the intervention, only the CST-IT group maintained its MMSE score, while the control group displayed deterioration. The CST-IT group also performed better in some of the cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive subscale and narrative language), mood measures (Cornell scale, social and emotional loneliness scale with a decrease in reported loneliness), and the Quality of life--Alzheimer's Disease scale. No other treatment effect was observed. CONCLUSIONS: The findings confirm the efficacy, at least in the short term, of the CST in sustaining cognitive functions and perceived quality of life in older adults with dementia in the Italian care setting as well. PMID- 27272539 TI - Quality Profiling at the TCM Hospital Bad Kotzting - Examples from an Ongoing Systematic Patient Documentation. AB - BACKGROUND: Quality profiling is practiced at the TCM hospital Bad Kotzting since its establishment 25 years ago. The profiling comprises assessment of treatment effectiveness andsafety, structural features, staff qualification as well as diagnostic and therapeutic processes. Findings regarding patients, intervention and outcome profiles are presented by appropriate examples. METHODS: Data of each in-patient were systematically collected by physicians and via self-reports at admission, discharge and follow-up. Over the years the system was adjusted several times resulting in a data pool of about 19,000 in-patients by end of 2014. RESULTS: Patients are 52 years old on average, 70% are female, and suffering from the main complaint since 7 years (median). The diagnostic spectrum changed over the years according to the development towards a psychosomatic focus. For TCM acupuncture therapy 222 different acupoints were used in 7.7 different localisations on average per individual treatment. The mean intensity of the main complaint decreased clinically relevant (Cohen's d = 1.11 at discharge and 0.93 at follow-up). After the hospital stay the number of days of sick leave declined from 51.3 days by 40% per patient and year. Depressive disorders as most common mental illness decreased significantly decreased significantly at discharge (ICD symptom rating; Cohen's d = -1.01). 29.8% of patients met the criteria for a metabolic syndrome diagnosis according to the International Diabetes Federation (IDF). In this group of cases, triglycerides, cholesterol and blood glucose improved markedly at discharge. DISCUSSION: The presented quality control measures clearly contribute to an enhanced transparency in terms of a comprehensive quality profile. The findings from various outcome parameters indicate that patients benefit from the treatment. PMID- 27272540 TI - A review of digital microfluidics as portable platforms for lab-on a-chip applications. AB - Following the development of microfluidic systems, there has been a high tendency towards developing lab-on-a-chip devices for biochemical applications. A great deal of effort has been devoted to improve and advance these devices with the goal of performing complete sets of biochemical assays on the device and possibly developing portable platforms for point of care applications. Among the different microfluidic systems used for such a purpose, digital microfluidics (DMF) shows high flexibility and capability of performing multiplex and parallel biochemical operations, and hence, has been considered as a suitable candidate for lab-on-a chip applications. In this review, we discuss the most recent advances in the DMF platforms, and evaluate the feasibility of developing multifunctional packages for performing complete sets of processes of biochemical assays, particularly for point-of-care applications. The progress in the development of DMF systems is reviewed from eight different aspects, including device fabrication, basic fluidic operations, automation, manipulation of biological samples, advanced operations, detection, biological applications, and finally, packaging and portability of the DMF devices. Success in developing the lab-on-a-chip DMF devices will be concluded based on the advances achieved in each of these aspects. PMID- 27272541 TI - Iodine Concentration and Optimization in Computed Tomography Angiography: Current Issues. AB - Computed tomography (CT) technology has seen a dramatic evolution in the recent past that has deeply changed the face of this diagnostic modality. Since the early days of helical single-slice and then multislice CT, CT angiography (CTA) has been one of the most technically demanding applications, both in terms of scanning technique and contrast medium (CM) injection protocol, due to the need to acquire a large amount of high-resolution data over a limited period corresponding to the peak contrast enhancement of the arterial system. Iodine concentration is one of the main determinants of arterial enhancement in CTA, and current low-osmolar and iso-osmolar nonionic CM for intravascular administration still come in a handful of molecules, but a relatively wide range of different iodine concentrations. This gives the opportunity to optimize CTA protocols as a function of several factors such as patient characteristics, CT technology, and CM features in an attempt to maximize the diagnostic yield of CTA examinations while considering patient safety and avoiding unnecessary extra costs. Our aim is to provide an up-to-date overview of the existing evidence on how changing iodine concentration can have an impact on CTA performance, especially with the use of state-of-the-art CT and power injector technology, in the perspective of improving patient care while minimizing overall exposure to iodinated CM and ionizing radiation. PMID- 27272542 TI - Systematic Evaluation of Amide Proton Chemical Exchange Saturation Transfer at 3 T: Effects of Protein Concentration, pH, and Acquisition Parameters. AB - OBJECTIVE: The goal of this work was to systematically evaluate the reproducibility of amide proton transfer chemical exchange saturation transfer (APT-CEST) at 3 T and its signal dependence on pH, protein concentration, and acquisition parameters. An in vitro system based on bovine serum albumin (BSA) was used, and its limitations were tested by comparing it to in vivo measurements. The contribution of small endogenous metabolites on the APT-CEST signal at 3 T was also investigated. In addition, the reliability of different z spectrum interpolations as well as the use of only a few frequency offset data points instead of a whole z-spectrum were tested. MATERIALS AND METHODS: We created both a BSA phantom at different concentrations and pH values and a metabolite phantom with different small molecules. Chemical exchange saturation transfer data were acquired using a 2-dimensional fast spoiled gradient-echo sequence with pulsed CEST preparation at different saturation durations and power levels. Healthy volunteer measurements were taken for comparison. Z-spectra were interpolated using a 24th-order polynomial (Poly), an eighth-order Fourier series (Fourier), and a smoothing Spline (sSpline) algorithm. To evaluate reduced data sets, only 6 to 14 frequency offsets of the z-spectrum were used and interpolated via a cubic Spline. Region of interest (ROI) evaluations were used to investigate the reproducibility of amide magnetization transfer ratio asymmetry [MTRasym(3.5 ppm)] and to analyze the MTRasym and z-spectra. RESULTS: Interscan standard deviations of MTRasym(3.5 ppm) were always below 0.3%. MTRasym(3.5 ppm) increased when the BSA concentrations increased and decreased when the pH increased. The amine MTRasym signal of small molecules was very small compared with BSA and was only detectable using short saturation times and higher power levels. The MTRasym(3.5 ppm) between BSA concentration steps and between nearly all pH steps was significantly different for all 3 fitting methods. The Fourier and sSpline methods showed no statistically significant differences; however, the results for the Poly method were significantly higher at some concentrations and pH values. Using only few frequency offsets resulted in less significant differences compared with fitting the complete z-spectrum. In general, MTRasym(3.5 ppm) of gray matter, white matter, and ventricle ROIs from volunteer scans increased with an increase in saturation power and partially decreased with an increase in saturation duration. Intra-ROI covariances of MTRasym(3.5 ppm) revealed the highest variations for Poly, whereas using reduced spectral data resulted in an increased signal variation. CONCLUSIONS: Amide proton transfer-CEST imaging is a highly reproducible method in which absolute signal differences of approximately 0.5% are detectable in principle. For in vivo applications, Fourier or sSpline interpolations of z-spectra are preferable. Using reduced data sets delivers similar results but with increased variation and therefore decreased (pH/concentration) differentiation capability. Differentiation capability increases with increases in the saturation duration and power level. The results from the in vitro BSA system cannot be directly transferred to the in vivo situation due to different chemical environments resulting in, for example, higher asymmetric macromolecular cMT effects in vivo. Amine signals from small molecules are unlikely to contribute to APT-CEST at 3 T (except for creatine); however, signals can be enhanced by using short saturation times and higher power levels. PMID- 27272543 TI - Effect of Renal Function on Gadolinium-Related Signal Increases on Unenhanced T1 Weighted Brain Magnetic Resonance Imaging. AB - OBJECTIVES: The purpose of this study was to determine if renal function affects signal changes in the deep brain nuclei on unenhanced T1-weighted images after administration of linear gadolinium-based contrast agents (GBCAs). METHODS: An electronic medical records search of 2 large medical centers identified 25 patients who received linear GBCA while on hemodialysis and had unenhanced T1 weighted images of the brain before and after. The dentate-to-cerebellar peduncle (DCP) ratio, globus pallidus-to-mid thalamus (GPT) ratio, and choroid plexus-to nearby white matter ratio were measured and compared with 25 age/sex/GBCA exposure-matched control patients with normal or near-normal renal function (estimated glomerular filtration rate >60 mL/min per 1.73 m). Two additional control groups included 13 patients on hemodialysis without GBCA exposure and 13 age/sex-matched patients with estimated glomerular filtration rate greater than 60 mL/min per 1.73 m. RESULTS: Hemodialysis patients (n = 25) with an average of 1.8 linear GBCA administrations had a 4.9% mean increase (1.00 +/- 0.04 vs 1.05 +/- 0.05; P < 0.001) in DCP, which was greater than the 1.6% change (0.99 +/- 0.04 vs 1.00 +/- 0.05; P = 0.08) observed in matched controls (P = 0.01). There was no significant signal change in the DCP ratio in the 13 hemodialysis patients (0.99 +/- 0.04 vs 0.99 +/- 0.04; P = 0.78) and 13 age/sex-matched patients (0.99 +/- 0.02 vs 0.99 +/- 0.03; P = 0.78) who did not receive GBCA. The hemodialysis patients had a baseline GPT that was higher than nondialysis patients (P < 0.001). However, the GPT change after GBCA administration was not significantly different from controls. Increased signal in the choroid plexus on unenhanced T1 weighted images after GBCA administration was noted in hemodialysis patients (0.72 +/- 0.20 vs 0.86 +/- 0.23; P = 0.006); however, a multivariate analysis showed this to be primarily related to hemodialysis (P = 0.003) with only a trend toward relating to GBCA exposure (P = 0.07). CONCLUSIONS: Hemodialysis patients receiving linear GBCA have greater dentate nucleus signal increases on unenhanced T1-weighted images, suggesting that renal function may affect the rate of gadolinium accumulation in the brain after linear GBCA-enhanced magnetic resonance imaging. PMID- 27272545 TI - [Not Available]. AB - By the food intake man is daily exposed to numerous chemical agents with impact on ageing and longevity. Over the last two centuries longevity in the affluent societies has increased by 2 years per decade. Improved food habits are important contributing factors. Dietary patterns of populations with long life-spans, like the traditional Mediterranean diet and the Okinawa Island diet, provide the basis to recommend plant foods like vegetables, legumes, fruits, non-tropical vegetable oils as basic fat, light meat (e.g. poultry) of moderate amounts, plenty of fish and moderate beverage intakes of wine, coffee and tea. Oxidative damage is suggested as one major reason for exaggerated ageing. Foods that promote longevity are rich in antioxidants. Still there is no evidence that extra anti oxidant supplementation has any beneficial effects. Energy balance to avoid obesity at young and middle ages, e.g. by calorie restricted diets and increased physical activity, promotes longevity, whereas at older age overweight is usually associated with a longer life-span. PMID- 27272544 TI - Bioactive Secondary Metabolites from Schizogyne sericea (Asteraceae) Endemic to Canary Islands. AB - Schizogyne sericea (Asteraceae) is a halophytic shrub endemic to the Canary Islands and traditionally employed as analgesic, astringent, anti-inflammatory, and vulnerary. A comprehensive phytochemical investigation was conducted on the flowering aerial parts by analyzing both essential oil constituents and polar compounds. The essential oil was dominated by p-cymene, with the noteworthy occurrence of beta-pinene and thymol esters. From the EtOH extract, eight compounds were isolated and structurally elucidated. Essential oil, polar fractions, and isolates (2), (4), and (5) were separately in vitro assayed for antiproliferative activity on human tumor cell lines (A375, MDA-MB 231, and HCT116) by MTT assay, for antioxidant potential by DPPH, ABTS, and FRAP assays, and for antimicrobial activity by the agar disk diffusion method. Results revealed that essential oil and compounds 1 and 2 exert a strong inhibition on tumor cells, and in some cases, higher than that of cisplatin. Fractions containing thymol derivatives (1 and 2) and caffeoylquinic acid derivatives 4 and 5 displayed antioxidant activity comparable to that of Trolox, making S. sericea extract an interesting natural product with potential applications as preservative or in the treatment of diseases in which oxidative stress plays an important role. PMID- 27272546 TI - [Not Available]. PMID- 27272547 TI - [Not Available]. PMID- 27272548 TI - [Not Available]. PMID- 27272549 TI - [Not Available]. PMID- 27272550 TI - Response to 'Darier disease in Israel: combined evaluation of genetic and neuropsychiatric aspects': reply from the authors. PMID- 27272553 TI - Corrigendum: Synthetic Developments of Nontoxic Quantum Dots. PMID- 27272554 TI - Erratum: The Significance of Rectus Femoris for the Favorable Functional Outcome After Total Femur Replacement: Erratum. AB - [This corrects the article DOI: 10.1097/GOX.0000000000000610.]. PMID- 27272551 TI - Discrimination of human faces by archerfish (Toxotes chatareus). AB - Two rival theories of how humans recognize faces exist: (i) recognition is innate, relying on specialized neocortical circuitry, and (ii) recognition is a learned expertise, relying on general object recognition pathways. Here, we explore whether animals without a neocortex, can learn to recognize human faces. Human facial recognition has previously been demonstrated for birds, however they are now known to possess neocortex-like structures. Also, with much of the work done in domesticated pigeons, one cannot rule out the possibility that they have developed adaptations for human face recognition. Fish do not appear to possess neocortex-like cells, and given their lack of direct exposure to humans, are unlikely to have evolved any specialized capabilities for human facial recognition. Using a two-alternative forced-choice procedure, we show that archerfish (Toxotes chatareus) can learn to discriminate a large number of human face images (Experiment 1, 44 faces), even after controlling for colour, head shape and brightness (Experiment 2, 18 faces). This study not only demonstrates that archerfish have impressive pattern discrimination abilities, but also provides evidence that a vertebrate lacking a neocortex and without an evolutionary prerogative to discriminate human faces, can nonetheless do so to a high degree of accuracy. PMID- 27272557 TI - Chromatographic analysis of Polygalae Radix by online hyphenating pressurized liquid extraction. AB - Practicing "green analytical chemistry" is of great importance when profiling the chemical composition of complex matrices. Herein, a novel hybrid analytical platform was developed for direct chemical analysis of complex matrices by online hyphenating pressurized warm water extraction followed by turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry (PWWE-TFC-LC-MS/MS). Two parallel hollow guard columns acted as extraction vessels connected to a long narrow polyether ether ketone tube, while warm water served as extraction solvent and was delivered at a flow rate of 2.5 mL/min to generate considerable back pressure at either vessel. A column oven heated both the solvent and crude materials. A TFC column, which is advantageous for the comprehensive trapping of small molecular substances from fluids under turbulent flow conditions, was employed to transfer analytes from the PWWE module to LC-MS/MS. Two electronic valves alternated each vessel between extraction and elution phases. As a proof-of-concept, a famous herbal medicine for the treatment of neurodegenerative disorders, namely Polygalae Radix, was selected for the qualitative and quantitative analyses. The results suggest that the hybrid platform is advantageous in terms of decreasing time, material, and solvent consumption and in its automation, versatility, and environmental friendliness. PMID- 27272555 TI - Fimasartan: A New Angiotensin Receptor Blocker. AB - Fimasartan is the ninth, and most recent, angiotensin II receptor antagonist approved as an antihypertensive agent. Fimasartan, a pyrimidin-4(3H)-one derivative of losartan with the imidazole ring replaced, which enables higher potency and longer duration than losartan. Fecal elimination and biliary excretion are the predominant elimination pathways of fimasartan and the urinary excretion was found to be less than 3 % 24 h after administration. Fimasartan is primarily catabolized by cytochrome P450 isoform 3A and no significant drug interaction was observed when used in combination with hydrochlorothiazide, amlodipine, warfarin, or digoxin. Fimasartan at a dosage range of 60-120 mg once daily showed an antihypertensive effect over 24 h. In a large, population-based observational study, fimasartan showed an excellent safety profile. Anti inflammatory and organ-protecting effects of fimasartan have been shown in various preclinical studies, including aortic balloon injury, myocardial infarct ischemia/reperfusion, doxorubicin cardiotoxicity, and ischemic stroke models. PMID- 27272558 TI - Wideband nonlinear spectral broadening in ultra-short ultra - silicon rich nitride waveguides. AB - CMOS-compatible nonlinear optics platforms with high Kerr nonlinearity facilitate the generation of broadband spectra based on self-phase modulation. Our ultra - silicon rich nitride (USRN) platform is designed to have a large nonlinear refractive index and low nonlinear losses at 1.55 MUm for the facilitation of wideband spectral broadening. We investigate the ultrafast spectral characteristics of USRN waveguides with 1-mm-length, which have high nonlinear parameters (gamma ~ 550 W(-1)/m) and anomalous dispersion at 1.55 MUm wavelength of input light. USRN add-drop ring resonators broaden output spectra by a factor of 2 compared with the bandwidth of input fs laser with the highest quality factors of 11000 and 15000. Two - fold self phase modulation induced spectral broadening is observed using waveguides only 430 MUm in length, whereas a quadrupling of the output bandwidth is observed with USRN waveguides with a 1-mm length. A broadening factor of around 3 per 1 mm length is achieved in the USRN waveguides, a value which is comparatively larger than many other CMOS-compatible platforms. PMID- 27272559 TI - Lay public mental models of ionizing radiation: representations and risk perception in four European countries. AB - How do members of the lay public understand ionizing radiation and its effects? How do they define ionizing radiation, and to which other concepts do they connect it? Do they perceive danger and risks? Do they know how to protect themselves? What do they think of various applications of ionizing radiation? Where and how does the public lodge confidence or doubt? What is the demand for information and transparency? We applied the mental models approach to investigate these questions in four European countries (France, Poland, Romania, and Slovenia; 63 respondents), providing a rich picture of how the lay public perceives ionizing radiation. Mental models are messy and overlapping but meaningful and useful schemas, resulting from a person's multidimensional experience and relation to the surrounding natural and social world. Collectively, members of the lay public (independently of their education or background) possess a non-negligible amount of knowledge on the topic of ionizing radiation risk, and hold strong views on related concepts. Mutual understanding between specialists and potentially affected citizens may be a critical pathway to build a shared and effective risk culture supported by accurate, two-way risk communication and inter-actor relationships. PMID- 27272560 TI - Potential Role of Reversion-Inducing Cysteine-Rich Protein with Kazal Motifs (RECK) in Regulation of Matrix Metalloproteinases (MMPs) Expression in Periodontal Diseases. AB - Periodontal diseases are characterized by pathological destruction of extracellular matrix (ECM) of periodontal tissues. Matrix metalloproteinases (MMPs) are a significant part of the degradation of ECM. However, the regulation of MMPs expression level in periodontal diseases is as yet undetermined. RECK (reversion-inducing cysteine-rich protein with Kazal motifs), a novel membrane anchored inhibitor of MMPs, could regulate the expressions of MMP-2, 9 and MT1 MMP as a cell surface-signaling molecule. Thus, we propose that RECK may play an important role in regulating MMPs in the ECM degradation of periodontal diseases. The RECK/MMPs signaling pathway could provide a new approach for prevention and treatment of RECK in periodontal diseases by blocking MMPs. PMID- 27272562 TI - Flexible Superhydrophobic and Superoleophilic MoS2 Sponge for Highly Efficient Oil-Water Separation. AB - Removal of oils and organic solvents from water is an important global challenge for energy conservation and environmental protection. Advanced sorbent materials with excellent sorption capacity need to be developed. Here we report on a superhydrophobic and superoleophilic MoS2 nanosheet sponge (SMS) for highly efficient separation and absorption of oils or organic solvents from water. This novel sponge exhibits excellent absorption performance through a combination of superhydrophobicity, high porosity, robust stability in harsh conditions (including flame retardance and inertness to corrosive and different temperature environments) and excellent mechanical properties. The dip-coating strategy proposed for the fabrication of the SMS, which does not require a complicated process or sophisticated equipment, is very straightforward and easy to scale up. This finding shows promise for water remediation and oil recovery. PMID- 27272561 TI - Mutation Profiling Indicates High Grade Prostatic Intraepithelial Neoplasia as Distant Precursors of Adjacent Invasive Prostatic Adenocarcinoma. AB - INTRODUCTION: High Grade Prostatic Intraepithelial Neoplasia (HGPIN) is the putative precursor lesion to prostatic adenocarcinoma (PCa), but the precise relationship between HGPIN and PCa remains unclear. METHODS: We performed a molecular case study in which we studied mutation profiles of six tumor associated HGPIN lesions in a single case of TMPRSS2:ERG fusion positive Gleason score 7 PCa that we had previously mapped for somatic mutations in adjacent Gleason patterns 3 and 4 foci, using microdissection and targeted deep sequencing. RESULTS: A total of 32 tumor-specific mutated sites were successfully amplified and sequenced, including 25 truncal mutations and 7 mutations that were specific to either the Gleason pattern 3 or pattern 4 foci. All six HGPIN foci shared the same tumor-specific TMPRSS2:ERG fusion breakpoint, establishing that they were all clonally related to the adjacent invasive tumor. Among the 32 gene targets mutated in the invasive tumor, only mutation of the OR2AP1 gene, a truncal mutation, was found in a single focus of HGPIN. The remaining gene targets that were successfully sequenced were wild-type in all other HGPIN foci. DISCUSSION: This study demonstrates the feasibility of targeted mutation profiling of HGPIN lesions, which will be important to understand PCa tumorigenesis. The results in this case, showing a remarkable absence of truncal mutations in HGPIN lesions bearing the tumor-specific ERG fusion, indicate HGPIN lesions may be relatively stable genetically and argue against a stepwise clonal evolution model of HGPIN to PCa. Prostate 76:1227-1236, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272563 TI - Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children. AB - BACKGROUND: People with asthma may experience exacerbations or "attacks" during which their symptoms worsen and additional treatment is required. Written action plans may advocate doubling the dose of inhaled steroids in the early stages of an asthma exacerbation to reduce the severity of the attack and to prevent the need for oral steroids or hospital admission. OBJECTIVES: To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids (ICS) as part of a patient-initiated action plan for home management of exacerbations in children and adults with persistent asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, which is derived from searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to March 2016. We handsearched respiratory journals and meeting abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared increased versus stable doses of ICS for home management of asthma exacerbations. We included studies of children or adults with persistent asthma who were receiving daily maintenance ICS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality and extracted data. We contacted authors of RCTs for additional information. MAIN RESULTS: This review update added three new studies including 419 participants to the review. In total, we identified eight RCTs, most of which were at low risk of bias, involving 1669 participants with mild to moderate asthma. We included three paediatric (n = 422) and five adult (n = 1247) studies; six were parallel-group trials and two had a cross-over design. All but one study followed participants for six months to one year. Allowed maintenance doses of ICS varied in adult and paediatric studies, as did use of concomitant medications and doses of ICS initiated during exacerbations. Investigators gave participants a study inhaler containing additional ICS or placebo to be started as part of an action plan for treatment of exacerbations.The odds of treatment failure, defined as the need for oral corticosteroids, were not significantly reduced among those randomised to increased ICS compared with those taking their usual stable maintenance dose (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.68 to 1.18; participants = 1520; studies = 7). When we analysed only people who actually took their study inhaler for an exacerbation, we found much variation between study results but the evidence did not show a significant benefit of increasing ICS dose (OR 0.84, 95% CI 0.54 to 1.30; participants = 766; studies = 7). The odds of having an unscheduled physician visit (OR 0.96, 95% CI 0.66 to 1.41; participants = 931; studies = 3) or acute visit (Peto OR 0.98, 95% CI 0.24 to 3.98; participants = 450; studies = 3) were not significantly reduced by an increased versus stable dose of ICS, and evidence was insufficient to permit assessment of impact on the duration of exacerbation; our ability to draw conclusions from these outcomes was limited by the number of studies reporting these events and by the number of events included in the analyses. The odds of serious events (OR 1.69, 95% CI 0.77 to 3.71; participants = 394; studies = 2) and non-serious events, such as oral irritation, headaches and changes in appetite (OR 2.15, 95% CI 0.68 to 6.73; participants = 142; studies = 2), were neither increased nor decreased significantly by increased versus stable doses of ICS during an exacerbation. Too few studies are available to allow firm conclusions on the basis of subgroup analyses conducted to investigate the impact of age, time to treatment initiation, doses used, smoking history and the fold increase of ICS on the magnitude of effect; yet, effect size appears similar in children and adults. AUTHORS' CONCLUSIONS: Current evidence does not support increasing the dose of ICS as part of a self initiated action plan to treat exacerbations in adults and children with mild to moderate asthma. Increased ICS dose is not associated with a statistically significant reduction in the odds of requiring rescue oral corticosteroids for the exacerbation, or of having adverse events, compared with a stable ICS dose. Wide confidence intervals for several outcomes mean we cannot rule out possible benefits of this approach. PMID- 27272568 TI - Woman at the Window: Caspar David Friedrich. PMID- 27272569 TI - The Stars of Hospital Care: Useful or a Distraction? PMID- 27272564 TI - Real-time intravital imaging of pH variation associated with osteoclast activity. AB - Intravital imaging by two-photon excitation microscopy (TPEM) has been widely used to visualize cell functions. However, small molecular probes (SMPs), commonly used for cell imaging, cannot be simply applied to intravital imaging because of the challenge of delivering them into target tissues, as well as their undesirable physicochemical properties for TPEM imaging. Here, we designed and developed a functional SMP with an active-targeting moiety, higher photostability, and a fluorescence switch and then imaged target cell activity by injecting the SMP into living mice. The combination of the rationally designed SMP with a fluorescent protein as a reporter of cell localization enabled quantitation of osteoclast activity and time-lapse imaging of its in vivo function associated with changes in cell deformation and membrane fluctuations. Real-time imaging revealed heterogenic behaviors of osteoclasts in vivo and provided insights into the mechanism of bone resorption. PMID- 27272576 TI - The Potential for Postrandomization Confounding in Randomized Clinical Trials. PMID- 27272565 TI - Copper regulates cyclic-AMP-dependent lipolysis. AB - Cell signaling relies extensively on dynamic pools of redox-inactive metal ions such as sodium, potassium, calcium and zinc, but their redox-active transition metal counterparts such as copper and iron have been studied primarily as static enzyme cofactors. Here we report that copper is an endogenous regulator of lipolysis, the breakdown of fat, which is an essential process in maintaining body weight and energy stores. Using a mouse model of genetic copper misregulation, in combination with pharmacological alterations in copper status and imaging studies in a 3T3-L1 white adipocyte model, we found that copper regulates lipolysis at the level of the second messenger, cyclic AMP (cAMP), by altering the activity of the cAMP-degrading phosphodiesterase PDE3B. Biochemical studies of the copper-PDE3B interaction establish copper-dependent inhibition of enzyme activity and identify a key conserved cysteine residue in a PDE3-specific loop that is essential for the observed copper-dependent lipolytic phenotype. PMID- 27272577 TI - A PIECE OF MY MIND. You've Got Mail. PMID- 27272578 TI - The Unrelenting Challenge of Obesity. PMID- 27272579 TI - Syphilis on the Rise: What Went Wrong? PMID- 27272580 TI - Trends in Obesity Among Adults in the United States, 2005 to 2014. AB - IMPORTANCE: Between 1980 and 2000, the prevalence of obesity increased significantly among adult men and women in the United States; further significant increases were observed through 2003-2004 for men but not women. Subsequent comparisons of data from 2003-2004 with data through 2011-2012 showed no significant increases for men or women. OBJECTIVE: To examine obesity prevalence for 2013-2014 and trends over the decade from 2005 through 2014 adjusting for sex, age, race/Hispanic origin, smoking status, and education. DESIGN, SETTING, AND PARTICIPANTS: Analysis of data obtained from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional, nationally representative health examination survey of the US civilian noninstitutionalized population that includes measured weight and height. EXPOSURES: Survey period. MAIN OUTCOMES AND MEASURES: Prevalence of obesity (body mass index >=30) and class 3 obesity (body mass index >=40). RESULTS: This report is based on data from 2638 adult men (mean age, 46.8 years) and 2817 women (mean age, 48.4 years) from the most recent 2 years (2013-2014) of NHANES and data from 21,013 participants in previous NHANES surveys from 2005 through 2012. For the years 2013-2014, the overall age-adjusted prevalence of obesity was 37.7% (95% CI, 35.8%-39.7%); among men, it was 35.0% (95% CI, 32.8%-37.3%); and among women, it was 40.4% (95% CI, 37.6%-43.3%). The corresponding prevalence of class 3 obesity overall was 7.7% (95% CI, 6.2%-9.3%); among men, it was 5.5% (95% CI, 4.0%-7.2%); and among women, it was 9.9% (95% CI, 7.5%-12.3%). Analyses of changes over the decade from 2005 through 2014, adjusted for age, race/Hispanic origin, smoking status, and education, showed significant increasing linear trends among women for overall obesity (P = .004) and for class 3 obesity (P = .01) but not among men (P = .30 for overall obesity; P = .14 for class 3 obesity). CONCLUSIONS AND RELEVANCE: In this nationally representative survey of adults in the United States, the age-adjusted prevalence of obesity in 2013-2014 was 35.0% among men and 40.4% among women. The corresponding values for class 3 obesity were 5.5% for men and 9.9% for women. For women, the prevalence of overall obesity and of class 3 obesity showed significant linear trends for increase between 2005 and 2014; there were no significant trends for men. Other studies are needed to determine the reasons for these trends. PMID- 27272581 TI - Trends in Obesity Prevalence Among Children and Adolescents in the United States, 1988-1994 Through 2013-2014. AB - IMPORTANCE: Previous analyses of obesity trends among children and adolescents showed an increase between 1988-1994 and 1999-2000, but no change between 2003 2004 and 2011-2012, except for a significant decline among children aged 2 to 5 years. OBJECTIVES: To provide estimates of obesity and extreme obesity prevalence for children and adolescents for 2011-2014 and investigate trends by age between 1988-1994 and 2013-2014. DESIGN, SETTING, AND PARTICIPANTS: Children and adolescents aged 2 to 19 years with measured weight and height in the 1988-1994 through 2013-2014 National Health and Nutrition Examination Surveys. EXPOSURES: Survey period. MAIN OUTCOMES AND MEASURES: Obesity was defined as a body mass index (BMI) at or above the sex-specific 95th percentile on the US Centers for Disease Control and Prevention (CDC) BMI-for-age growth charts. Extreme obesity was defined as a BMI at or above 120% of the sex-specific 95th percentile on the CDC BMI-for-age growth charts. Detailed estimates are presented for 2011-2014. The analyses of linear and quadratic trends in prevalence were conducted using 9 survey periods. Trend analyses between 2005-2006 and 2013-2014 also were conducted. RESULTS: Measurements from 40,780 children and adolescents (mean age, 11.0 years; 48.8% female) between 1988-1994 and 2013-2014 were analyzed. Among children and adolescents aged 2 to 19 years, the prevalence of obesity in 2011 2014 was 17.0% (95% CI, 15.5%-18.6%) and extreme obesity was 5.8% (95% CI, 4.9% 6.8%). Among children aged 2 to 5 years, obesity increased from 7.2% (95% CI, 5.8%-8.8%) in 1988-1994 to 13.9% (95% CI, 10.7%-17.7%) (P < .001) in 2003-2004 and then decreased to 9.4% (95% CI, 6.8%-12.6%) (P = .03) in 2013-2014. Among children aged 6 to 11 years, obesity increased from 11.3% (95% CI, 9.4%-13.4%) in 1988-1994 to 19.6% (95% CI, 17.1%-22.4%) (P < .001) in 2007-2008, and then did not change (2013-2014: 17.4% [95% CI, 13.8%-21.4%]; P = .44). Obesity increased among adolescents aged 12 to 19 years between 1988-1994 (10.5% [95% CI, 8.8% 12.5%]) and 2013-2014 (20.6% [95% CI, 16.2%-25.6%]; P < .001) as did extreme obesity among children aged 6 to 11 years (3.6% [95% CI, 2.5%-5.0%] in 1988-1994 to 4.3% [95% CI, 3.0%-6.1%] in 2013-2014; P = .02) and adolescents aged 12 to 19 years (2.6% [95% CI, 1.7%-3.9%] in 1988-1994 to 9.1% [95% CI, 7.0%-11.5%] in 2013 2014; P < .001). No significant trends were observed between 2005-2006 and 2013 2014 (P value range, .09-.87). CONCLUSIONS AND RELEVANCE: In this nationally representative study of US children and adolescents aged 2 to 19 years, the prevalence of obesity in 2011-2014 was 17.0% and extreme obesity was 5.8%. Between 1988-1994 and 2013-2014, the prevalence of obesity increased until 2003 2004 and then decreased in children aged 2 to 5 years, increased until 2007-2008 and then leveled off in children aged 6 to 11 years, and increased among adolescents aged 12 to 19 years. PMID- 27272583 TI - Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: US Preventive Services Task Force Recommendation Statement. AB - IMPORTANCE: In 2014, 19,999 cases of syphilis were reported in the United States. Left untreated, syphilis can progress to late-stage disease in about 15% of persons who are infected. Late-stage syphilis can lead to development of inflammatory lesions throughout the body, which can lead to cardiovascular or organ dysfunction. Syphilis infection also increases the risk for acquiring or transmitting HIV infection. OBJECTIVE: To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for syphilis infection in nonpregnant adults. Screening for syphilis in pregnant women was updated in a separate recommendation statement in 2009 (A recommendation). EVIDENCE REVIEW: The USPSTF reviewed the evidence on screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents, including patients coinfected with other sexually transmitted infections (such as HIV). FINDINGS: The USPSTF found convincing evidence that screening for syphilis infection in asymptomatic, nonpregnant persons at increased risk for infection provides substantial benefit. Accurate screening tests are available to identify syphilis infection in populations at increased risk. Effective treatment with antibiotics can prevent progression to late-stage disease, with small associated harms, providing an overall substantial health benefit. CONCLUSIONS AND RECOMMENDATION: The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation). PMID- 27272584 TI - Screening for Syphilis: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. AB - IMPORTANCE: Screening for syphilis infection is currently recommended for high risk individuals, including those with previous syphilis infection, an infected sexual partner, HIV infection, or more than 4 sex partners in the preceding year. OBJECTIVE: To update a 2004 systematic review of studies of syphilis screening effectiveness, test accuracy, and screening harms in nonpregnant adults and adolescents. DATA SOURCES: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews through October 2015 and Ovid MEDLINE (January 2004 to October 2015), with updated search through March 2016. STUDY SELECTION: English-language trials and observational studies of screening effectiveness, test accuracy, and screening harms in nonpregnant adults and adolescents. DATA EXTRACTION AND SYNTHESIS: One investigator abstracted data, a second checked data for accuracy, and 2 investigators independently assessed study quality using predefined criteria. MAIN OUTCOMES AND MEASURES: Transmission of disease, including HIV; complications of syphilis; diagnostic accuracy; and harms of screening. RESULTS: No evidence was identified regarding the effectiveness of screening on clinical outcomes or the effectiveness of risk assessment instruments; the harms of screening; or the effectiveness of screening in average-risk, nonpregnant adolescents or adults or high-risk individuals other than men who have sex with men (MSM) or men who are HIV positive. Four non-US studies indicated higher rates of syphilis detection with screening every 3 months vs 6 or 12 months for early syphilis in HIV-positive men or MSM. For example, there was an increased proportion of asymptomatic, higher-risk MSM in Australia (n = 6789 consultations) receiving a diagnosis of early syphilis when tested every 3 months vs annually (53% vs 16%, P = .001), but no difference among low-risk MSM. Treponemal and nontreponemal tests were accurate in asymptomatic individuals (sensitivity >85%, specificity >91%) in 3 studies but required confirmatory testing. Reverse sequence testing with an initial automated treponemal test yielded more false reactive test results than with rapid plasma reagin in 2 studies, one with a low-prevalence US population (0.6% vs 0.0%, P = .03) and another in a higher-prevalence Canadian population (0.26% vs 0.13%). CONCLUSIONS AND RELEVANCE: Screening HIV-positive men or MSM for syphilis every 3 months is associated with improved syphilis detection. Treponemal or nontreponemal tests are accurate screening tests but require confirmation. Research is needed on the effect of screening on clinical outcomes; effective screening strategies, including reverse sequence screening, in various patient populations; and harms of screening. PMID- 27272582 TI - Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. AB - IMPORTANCE: Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand. OBJECTIVE: To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. DESIGN, SETTING, AND PARTICIPANTS: Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. EXPOSURES: A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. RESULTS: Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = -0.2 (95% CI, -2.6 to 2.9); performance = 0.5 (95% CI, -2.7 to 3.7); and verbal = -0.5 (95% CI, -3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. CONCLUSIONS AND RELEVANCE: Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed. PMID- 27272585 TI - Minimal Physical Health Risk Associated With Long-term Cannabis Use--But Buyer Beware. PMID- 27272586 TI - Treatment of Fatigue in Parkinson Disease. AB - CLINICAL QUESTION: Which pharmacological and nonpharmacological interventions are associated with improvement in general, physical, or mental fatigue and minimal adverse effects in patients with Parkinson disease (PD)? BOTTOM LINE: Rasagiline, modafinil, and doxepin are associated with improvement in fatigue and are not associated with increased risk of adverse effects in patients with PD. However, the quality of evidence is limited and does not provide a clear basis for treatment decisions. PMID- 27272587 TI - Trends in Gout and Rheumatoid Arthritis Hospitalizations in the United States, 1993-2011. PMID- 27272588 TI - Resident Physicians With Depression or Depressive Symptoms. PMID- 27272589 TI - Resident Physicians With Depression or Depressive Symptoms--In Reply. PMID- 27272590 TI - Treatment for Patients With Newly Diagnosed Glioblastoma. PMID- 27272591 TI - Treatment for Patients With Newly Diagnosed Glioblastoma--Reply. PMID- 27272592 TI - China's One-Child Policy. PMID- 27272593 TI - Consequences of Influencing Physician Behavior. PMID- 27272594 TI - China's One-Child Policy--In Reply. PMID- 27272595 TI - Responding to a Request for Physician-Assisted Death. PMID- 27272596 TI - Consequences of Influencing Physician Behavior--Reply. PMID- 27272597 TI - Responding to a Request for Physician-Assisted Death--Reply. PMID- 27272599 TI - The Significance of Mortality Statistics. PMID- 27272600 TI - JAMA PATIENT PAGE. Screening for Syphilis. PMID- 27272601 TI - Multifunctional metasurface lens for imaging and Fourier transform. AB - A metasurface can manipulate light in a desirable manner by imparting local and space-variant abrupt phase change. Benefiting from such an unprecedented capability, the conventional concept of what constitutes an optical lens continues to evolve. Ultrathin optical metasurface lenses have been demonstrated based on various nanoantennas such as V-shape structures, nanorods and nanoslits. A single device that can integrate two different types of lenses and polarities is desirable for system integration and device miniaturization. We experimentally demonstrate such an ultrathin metasurface lens that can function either as a spherical lens or a cylindrical lens, depending on the helicity of the incident light. Helicity-controllable focal line and focal point in the real focal plane, as well as imaging and 1D/2D Fourier transforms, are observed on the same lens. Our work provides a unique tool for polarization imaging, image processing and particle trapping. PMID- 27272602 TI - Optimized automated data analysis for the cytokinesis-block micronucleus assay using imaging flow cytometry for high throughput radiation biodosimetry. AB - The cytokinesis-block micronucleus (CBMN) assay is a well-established technique that can be employed in triage radiation biodosimetry to estimate whole body doses of radiation to potentially exposed individuals through quantitation of the frequency of micronuclei (MN) in binucleated lymphocyte cells (BNCs). The assay has been partially automated using traditional microscope-based methods and most recently has been modified for application on the ImageStream(X) (IS(X) ) imaging flow cytometer. This modification has allowed for a similar number of BNCs to be automatically scored as compared to traditional microscopy in a much shorter time period. However, the MN frequency measured was much lower than both manual and automated slide-based methods of performing the assay. This work describes the optimized analysis template which implements newly developed functions in the IDEAS((r)) data analysis software for the IS(X) that enhances specificity for BNCs and increases the frequency of scored MN. A new dose response calibration curve is presented in which the average rate of MN per BNC is of similar magnitude to those presented in the literature using automated CBMN slide scoring methods. In addition, dose estimates were generated for nine irradiated, blinded samples and were found to be within +/-0.5 Gy of the delivered dose. Results demonstrate that the improved identification accuracy for MN and BNCs in the IS(X) -based version of the CBMN assay will translate to increased accuracy when estimating unknown radiation doses received by exposed individuals following large-scale radiological or nuclear emergencies. (c) 2016 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC. PMID- 27272603 TI - Parental presence at anaesthesia induction: A systematic review. AB - This systematic review assessed the effectiveness of parental presence for children undergoing surgical or diagnostic procedures under general anaesthesia (such as bronchoscopy, laryngoscopy and laparoscopy). Randomized and quasi randomized trials with healthy children scheduled for elective diagnostic and surgical procedures under general anaesthesia (age range 0-16 years) where the intervention was parental presence at anaesthesia induction were included. A comprehensive literature search was conducted using electronic databases and the reference lists of included studies. The Cochrane collaboration's tool for assessing risk of bias was used for assessment of risk of bias. The Review Manager software was used to analyse and synthesize data. A random-effect meta analysis was used when there was evidence of clinical and/or statistical heterogeneity. Of the 102 citations identified, nine trials involving 1021 children were eligible for inclusion. Only four were sufficient to be included in the meta-analysis. There was no statistically significant difference on average in the level of anxiety in children and their parents either at separation or at induction between children allocated to parental presence and those allocated to no presence, premedication or parental presence plus premedication groups. Significant debate still surrounds this issue, and future trials should focus on the use of reliable and validated tools in assessing outcome measures. PMID- 27272604 TI - Mesophilic Acidogenesis of Food Waste-Recycling Wastewater: Effects of Hydraulic Retention Time, pH, and Temperature. AB - The effects of hydraulic retention time (HRT), pH, and operating temperature (T OP) on the degradation of food waste-recycling wastewater (FRW) were investigated in laboratory-scale hydrolysis/acidogenesis reactors. Response surface analysis was used to approximate the production of volatile organic acids and degradation of volatile suspended solids (VSS), carbohydrate, protein, and lipid with regard to the independent variables (1 <= HRT <= 3 days, 4 <= pH <= 6, 25 <= T OP <= 45 degrees C). Partial cubic models adequately approximated the corresponding response surfaces at alpha < 5 %. The physiological conditions for maximum acidification (0.4 g TVFA + EtOH/g VSadded) and the maximal degradation of VSS (47.5 %), carbohydrate (92.0 %), protein (17.7 %), and lipid (73.7 %) were different. Analysis of variance suggested that pH had a great effect on the responses in most cases, while T OP and HRT, and their interaction, were significant in some cases. Denaturing gradient gel electrophoresis analysis revealed that Sporanaerobacter acetigenes, Lactobacillus sp., and Eubacterium pyruvivorans-like microorganisms might be main contributors to the hydrolysis and acidogenesis of FRW. Biochemical methane potential test confirmed higher methane yield (538.2 mL CH4/g VSadded) from an acidogenic effluent than from raw FRW. PMID- 27272607 TI - Associations between parents' perception of neighbourhood environments and safety with physical activity of primary school children in Klang, Selangor, Malaysia. AB - BACKGROUND: This study aimed to evaluate parental perception of neighbourhood environments and safety in association with children's physical activity among primary school children in Klang, Selangor, Malaysia. METHODS: A total of 250 children (9-12 years of age) and their parents participated in this cross sectional study. Physical Activity Questionnaire for Older Children and Neighbourhood Environmental Walkability Scale as well as questions on constrained behaviours (avoidance and defensive behaviours) were used to assess the children's physical activity and parental perception of neighbourhood environment and safety, respectively. RESULTS: More than one-third (36.0%) of the children were physically inactive compared with only a small percentage (4.8%) who were physically active, with boys achieving higher physical activity levels than girls (t = 2.564, P = 0.011). For the environmental scale, parents' perception of land use mix (access) (r = 0.173, P = 0.006), traffic hazards (r = -0.152, P = 0.016) and defensive behaviour (r = -0.024, P = 0.143) correlated significantly with children's physical activity. In multiple linear regression analysis, child's gender (beta = -0.226; P = 0.003), parent's education (beta = 0.140; P = 0.001), household income (beta = 0.151; P = 0.024), land-use mix (access) (beta = 0.134; P = 0.011) and defensive behaviour (beta = -0.017; P = 0.038) were significantly associated with physical activity in children (R = 0.349, F = 6.760; P < 0.001), contributing 12.2% of the variances in physical activity of the children. CONCLUSION: Results highlight the links between parental perception of neighbourhood environments, safety and constrained behaviours with their children's participation in active play. Interventions aimed to increase actual and perceived safety and reduce perceptions of risk by parents in safe neighbourhoods can be targeted to increase children's physical activity in their local neighbourhoods. PMID- 27272609 TI - Current Literature. PMID- 27272608 TI - Effectiveness and cost-effectiveness of a brief school-based group programme for parents of children at risk of ADHD: a cluster randomised controlled trial. AB - BACKGROUND: National Institute for Health and Care Excellence guidelines recommend a stepped care approach for the identification and management of children with, or at risk of, attention-deficit/hyperactivity disorder (ADHD). We investigated the effectiveness, cost-effectiveness and acceptability of a group parenting intervention programme (+/- a teacher session) for children at risk of ADHD. METHODS: In a three-arm cluster randomised controlled trial, 12 primary schools were randomly assigned to control, parent-only and combined (parent + teacher) intervention arms. Eligible children had high levels of parent-rated hyperactivity/inattention (n = 199). At 6 month follow-up, the primary outcome measure was the parent-completed Conners' Rating Scale - Revised (ADHD index). Secondary outcomes included the Conners' sub-scales (hyperactivity, cognitive problems/inattention and oppositional behaviour), the teacher-completed Conners' Rating Scale - Revised, child health-related quality of life, parental burden and parental mental health. The cost-effectiveness analyses reflected a health and personal social services perspective. TRIAL REGISTRATION: ISRCTN87634685. RESULTS: Follow-up data were obtained from 76 parents and 169 teachers. There was no effect of the parent-only (mean difference = -1.1, 95% CI -5.1,2.9; p = 0.57) or combined interventions (mean difference = -2.1, 95% CI -6.4,2.1; p = 0.31) on the ADHD index. The combined intervention was associated with reduced parent reported hyperactivity symptoms (mean difference = -5.3; 95% CI -10.5,-0.01; p = 0.05) and the parent-only intervention with improved parental mental health (mean difference = -1.9; 95% CI -3.2,-0.5; p = 0.009). The incremental costs of the parent-only and the combined interventions were L73 and L123, respectively. Above a willingness-to-pay of L31 per one-point improvement in the ADHD index, the parent-only programme had the highest probability of cost-effectiveness. Participants found the interventions acceptable. CONCLUSIONS: For children at risk of ADHD, this school-based parenting programme was not associated with improvement in core ADHD symptoms. Secondary analyses suggested a possible reduction in parent-reported hyperactivity and parental mental health problems. Future research should compare targeted interventions against watchful waiting and specialist referral. PMID- 27272610 TI - Low palaeoelevation of the northern Lhasa terrane during late Eocene: Fossil foraminifera and stable isotope evidence from the Gerze Basin. AB - The Lhasa terrane is a key region for understanding the paleoelevation of the southern Tibetan Plateau after India-Asia collision. The Gerze Basin, located in the northern part of the Lhasa terrane, is a shortening-related basin. We discovered Lagena laevis (Bandy) fossils in upper Eocene strata of the Gerze Basin. This type of foraminifera is associated with lagoon and estuarine environments, indicating that the northern part of the Lhasa terrane was near sea level during the late Eocene. We speculate that these foraminifera were transported inland by storm surges to low elevation freshwater lakes during times of marine transgressions. This inference is consistent with the relatively positive delta(18)O values in carbonate from the same deposits that indicate low palaeoelevations close to sea level. Considering the palaeoelevation results from the nearby Oligocene basins at a similar latitude and the volcanic history of the Lhasa terrane, we infer that large-magnitude surface uplift of the northern Lhasa terrane occurred between late Eocene and late Oligocene time. PMID- 27272612 TI - Mother and Child: Medication Use in Pregnancy and Lactation. AB - Pregnancy and breastfeeding pose a unique challenge to drug development and clinical application. In addition to drug toxicity to the fetus in utero and infants through breastfeeding, alterations of pharmacokinetics in those women also need careful attention. How do we turn around the overall lack of drug efficacy and toxicity information for pregnant and breastfeeding women? PMID- 27272615 TI - Successful treatment of refractory Darier disease with alitretinoin with a follow up of over a year: a case report. PMID- 27272616 TI - How feedback, motor imagery, and reward influence brain self-regulation using real-time fMRI. AB - The learning process involved in achieving brain self-regulation is presumed to be related to several factors, such as type of feedback, reward, mental imagery, duration of training, among others. Explicitly instructing participants to use mental imagery and monetary reward are common practices in real-time fMRI (rtfMRI) neurofeedback (NF), under the assumption that they will enhance and accelerate the learning process. However, it is still not clear what the optimal strategy is for improving volitional control. We investigated the differential effect of feedback, explicit instructions and monetary reward while training healthy individuals to up-regulate the blood-oxygen-level dependent (BOLD) signal in the supplementary motor area (SMA). Four groups were trained in a two-day rtfMRI-NF protocol: GF with NF only, GF,I with NF + explicit instructions (motor imagery), GF,R with NF + monetary reward, and GF,I,R with NF + explicit instructions (motor imagery) + monetary reward. Our results showed that GF increased significantly their BOLD self-regulation from day-1 to day-2 and GF,R showed the highest BOLD signal amplitude in SMA during the training. The two groups who were instructed to use motor imagery did not show a significant learning effect over the 2 days. The additional factors, namely motor imagery and reward, tended to increase the intersubject variability in the SMA during the course of training. Whole brain univariate and functional connectivity analyses showed common as well as distinct patterns in the four groups, representing the varied influences of feedback, reward, and instructions on the brain. Hum Brain Mapp 37:3153-3171, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272619 TI - Simplification of Insulin Regimens in Patients With Type 2 Diabetes. PMID- 27272618 TI - Synthetic Nucleosomes Reveal that GlcNAcylation Modulates Direct Interaction with the FACT Complex. AB - Transcriptional regulation can be established by various post-translational modifications (PTMs) on histone proteins in the nucleosome and by nucleobase modifications on chromosomal DNA. Functional consequences of histone O GlcNAcylation (O-GlcNAc=O-linked beta-N-acetylglucosamine) are largely unexplored. Herein, we generate homogeneously GlcNAcylated histones and nucleosomes by chemical post-translational modification. Mass-spectrometry-based quantitative interaction proteomics reveals a direct interaction between GlcNAcylated nucleosomes and the "facilitates chromatin transcription" (FACT) complex. Preferential binding of FACT to GlcNAcylated nucleosomes may point towards O-GlcNAcylation as one of the triggers for FACT-driven transcriptional control. PMID- 27272620 TI - Morphology and clinical importance of epidural membrane and periradicular fibrous tissue in lumbar spinal stenosis. AB - PURPOSE: Compared to the ligamentum flavum (LF), morphology of the epidural membrane (EM) and the periradicular fibrous tissue (PRFT) has been largely ignored in studies of lumbar spinal stenosis (LSS). The aim of this prospective study was to elucidate the morphologies and clinical importance of the EM and PRFT in LSS. METHODS: Before starting this study, neural compressive EM (c-EM) and PRFT (c-PRFT) were defined as follows based on our microsurgical experience and a literature review. The c-EM is a constriction band or membrane obstructing dural tube expansion, and the c-PRFT is a fibrous tissue that compresses the nerve root and/or restricts its mobility. This study enrolled 134 patients who underwent microscopic decompression at L4/5. The morphologies of each patient's EM and PRFT were observed and recorded. Specimens were obtained from randomly selected patients for histological evaluation. RESULTS: The EM and PRFT exhibited a wide morphological spectrum, from a fine strand to a substantial membrane. The c-EM alone was observed in four cases, the c-PRFT alone in 37 cases, and both in three cases. The c-PRFT was more frequently observed in patients with degenerative spondylolisthesis than in those without olisthesis (P < 0.05). Several cases exhibited interesting histological findings including many small arteries, chondrometaplasia, ganglion-like cyst formation, and hyalinized collagen fibers. CONCLUSIONS: Some EM and PRFT transform into degenerative and substantial fibrous tissues during the process of symptomatic LSS development. Such morphological and histological changes can cause dural tear, symptomatic epidural hematoma, and/or inadequate decompression. PMID- 27272621 TI - Unilateral tubular approach for bilateral laminotomy: effect on ipsilateral and contralateral buttock and leg pain. AB - PURPOSE: Tubular laminotomy is an effective procedure for treatment of lumbar spinal stenosis (LSS) and lateral recesses stenosis. Most surgeons familiar with the procedure agree that the tubular approach appears to afford a more complete decompression of the contralateral thecal sac and nerve root, as compared to the ipsilateral approach. With this study we sought to answer the question whether this is reflected in clinically significant differences between the ipsilateral and contralateral side pain improvements. METHODS: In a retrospective case study, patients with LSS and lateral recesses stenosis who started out with VAS scores that were similar on the right and left side were included. All patients underwent a tubular (MIS) "over the top" laminotomy from a unilateral approach and through one incision. Surgeries were performed by a single surgeon in a single center. At the last follow-up, the extent of VAS score improvement on the approach (ipsilateral) side was compared to that of the contralateral side. RESULTS: Thirty-three patients were included in. At the latest follow-up of 25.8 +/- 3.4 months, there were statistically significant improvements in ODI and back VAS scores (p = 0.002 and p < 0.0001, respectively). In addition, buttock VAS scores were significantly improved both on the ipsilateral and the contralateral side (p < 0.001, and p = 0.001, respectively). Similarly, leg VAS scores were improved significantly on both sides (p < 0.001, and p = 0.001, respectively). There were no statistically significant differences between the extent of pain improvement on the ipsilateral and the contralateral side. CONCLUSIONS: MIS tubular laminotomy through a unilateral approach results in clinically effective bilateral decompression of LSS and lateral recesses, regardless of the approach side. PMID- 27272622 TI - Factors Associated with Early Mortality in HIV-Positive Men and Women Investigated for Tuberculosis at Ethiopian Health Centers. AB - INTRODUCTION: Despite increasing access to antiretroviral treatment (ART) in low income countries, HIV-related mortality is high, especially in the first months following ART initiation. We aimed to evaluate the impact of TB coinfection on early mortality and to assess gender-specific predictors of mortality in a cohort of Ethiopian adults subjected to intensified casefinding for active TB before starting ART. MATERIAL AND METHODS: Prospectively recruited ART-eligible adults (n = 812, 58.6% female) at five Ethiopian health centers were followed for 6 months. At inclusion sputum culture, Xpert MTB/RIF, and smear microscopy were performed (158/812 [19.5%] had TB). Primary outcome was all-cause mortality. We used multivariate Cox models to identify predictors of mortality. RESULTS: In total, 37/812 (4.6%) participants died, 12 (32.4%) of whom had TB. Karnofsky performance score (KPS) and mid-upper arm circumference (MUAC) were associated with mortality in the whole population. However, the associations were different in men and women. In men, only MUAC remained associated with mortality (adjusted hazard ratio [aHR] 0.71 [95% CI 0.57-0.88]). In women, KPS <80% was associated with mortality (aHR 10.95 [95% CI 2.33-51.49]), as well as presence of cough (aHR 3.98 [95% CI 1.10-14.36]). Cough was also associated with mortality for TB cases (aHR 8.30 [95% CI 1.06-65.14]), but not for non-TB cases. CONCLUSIONS: In HIV positive Ethiopian adults managed at health centers, mortality was associated with reduced performance score and malnutrition, with different distribution with regard to gender and TB coinfection. These robust variables could be used at clinic registration to identify persons at increased risk of early mortality. PMID- 27272625 TI - How Zika virus made the transition from being a virtually unknown virus to a high profile public health threat. PMID- 27272626 TI - Nurture in the neonatal intensive care unit. PMID- 27272623 TI - Stenosis triggers spread of helical Pseudomonas biofilms in cylindrical flow systems. AB - Biofilms are multicellular bacterial structures that adhere to surfaces and often endow the bacterial population with tolerance to antibiotics and other environmental insults. Biofilms frequently colonize the tubing of medical devices through mechanisms that are poorly understood. Here we studied the helicoidal spread of Pseudomonas putida biofilms through cylindrical conduits of varied diameters in slow laminar flow regimes. Numerical simulations of such flows reveal vortical motion at stenoses and junctions, which enhances bacterial adhesion and fosters formation of filamentous structures. Formation of long, downstream-flowing bacterial threads that stem from narrowings and connections was detected experimentally, as predicted by our model. Accumulation of bacterial biomass makes the resulting filaments undergo a helical instability. These incipient helices then coarsened until constrained by the tubing walls, and spread along the whole tube length without obstructing the flow. A three dimensional discrete filament model supports this coarsening mechanism and yields simulations of helix dynamics in accordance with our experimental observations. These findings describe an unanticipated mechanism for bacterial spreading in tubing networks which might be involved in some hospital-acquired infections and bacterial contamination of catheters. PMID- 27272627 TI - It is important with developmental supportive interventions beyond the NICU period. PMID- 27272628 TI - Impact of a systematic neonatal pain and sedation protocol. PMID- 27272629 TI - Revisiting a dilemma: repetitive pain vs. opioid exposures? PMID- 27272630 TI - Value-based recruitment in midwifery: do the values align with what women say is important to them? AB - AIM: The aim of this study was to discuss theoretical conceptualization and definition of values and value-based recruitment in the context of women's views about what they would like from their midwife. BACKGROUND: Value-based recruitment received headline status in the UK government's response to pervasive deficiencies in compassionate care identified in the health service. Core values which aim to inform service user's experience are defined in the National Health Service Constitution but clarity about whether these encompass all that women say is important to them is needed. DESIGN: Discussion paper. DATA SOURCES: A literature search included published papers written in English relating to values, VBR and women's views of a 'good' midwife with no date limiters. DISCUSSION: Definitions of values and value-based recruitment are examined. Congruence is explored between what women say is important to them and key government and professional regulatory documentation. The importance of a 'sustainable emotional' dimension in the midwife-mother relationship is suggested. CONCLUSION: Inconsistencies are identified between women's views, government, professional documentation and what women say they want. An omission of any reference to emotions or emotionality in value-based recruitment policy, professional recruitment and selection guidance documentation is identified. IMPLICATIONS: A review of key professional documentation, in relation to selection for 'values', is proposed. We argue for clarity and revision so that values embedded in value-based recruitment are consistent with health service users' views. An enhancement of the 'values' in the value-based recruitment framework is recommended to include the emotionality that women state is a fundamental part of their relationship with their midwife. PMID- 27272631 TI - Longitudinal Reciprocal Relationships Between Quality of Life and Coping Strategies Among Women with Breast Cancer. AB - BACKGROUND: Research on quality of life (QoL) among women with breast cancer has often examined the impact of coping strategies on QoL. However, the transactional model of stress and coping would argue that QoL can impact coping. This reciprocal relationship between QoL and coping has been inadequately studied. PURPOSE: This study examined reciprocal relationships over 18 months between QoL and coping (positive and negative coping) among women with breast cancer. METHODS: Three-wave cross-lagged structural equation modelling (SEM) analysis was used over three timepoints post-diagnosis (T1-T3; N = 637, 577, 553, respectively). RESULTS: SEM results revealed a significant reciprocal relationship between negative coping and QoL, indicating that negative coping predicted subsequent QoL, which in turn predicted later negative coping. Although QoL at cancer diagnosis predicted subsequent positive coping, we did not find a reciprocal relation between QoL and positive coping. CONCLUSION: Findings expand our knowledge of the relation between QoL and coping by suggesting the reciprocal relationship between negative coping and QoL among women with breast cancer. PMID- 27272632 TI - [Hygiene in ophthalmological practices : Results from ophthalmological practices in Frankfurt am Main in 2012-2015]. AB - BACKGROUND: Hygiene regulations must be taken into consideration for all diagnostic and therapeutic measures in order to avoid transfer of pathogens and infections. The Infection Protection Act assigns the responsibility for prevention of infections to managers of medical institutions, i.e. the owners of a practice and public health authorities are obligated to counsel and monitor medical institutions with respect to hygiene and prevention of infections. This article presents the results of the surveillance of all ophthalmological practices in Frankfurt am Main in 2012-2015, which are assessed and discussed against the background of the valid recommendations of the Committee for Hospital Hygiene (KRINKO). METHODS: Based on a checklist, all 35 ophthalmological practices in Frankfurt am Main received counseling and were monitored by an official from the Public Health Office. RESULTS: The basic principles of hygiene organization as well as the prerequisites for appropriate hand hygiene and surface disinfection were present in the majority of practices. In 11 practices (31.4 %) disposable medical products were exclusively utilized but medical products were prepared in-house in 24 practices (68.6 %). Contact pads for tonometry were prepared in-house in 13 (37.1 %) practices of which 6 were deficient so that improvements had to be implemented. In 6 out of the 7 practices where even critical medical products were prepared, this preparation was prohibited due to significant errors and the practices had to switch to disposable materials. DISCUSSION: In total, the practices could be certified as having a good general level of hygiene; however, in some cases major errors were found in the preparation of medical products, which had to be immediately corrected. PMID- 27272634 TI - [Conjunctival dehiscence following vitreoretinal surgery]. PMID- 27272633 TI - [Compliance of age related macular degeneration patients undergoing anti-VEGF therapy : Analysis and suggestions for improvement]. AB - BACKGROUND: Activity-based treatment regimens with anti-vascular endothelial growth factor (anti-VEGF) are currently the gold standard for treatment of exudative age-related macular degeneration (nAMD). Whereas injection frequencies of approximately seven injections in the first year and six in the second year are expected with a pro re nata (PRN) regimen, retrospective real life observations have recorded significantly reduced numbers of injections. This study was carried out to investigate the reasons for the reduction in follow-up control appointments and to find out whether a telemedicine network could influence the motivation and compliance for regular control examinations and treatment. MATERIAL AND METHODS: The patient collective included 210 eyes from 191 patients with nAMD treated by anti-VEGF therapy in 2010 and 2011. The activity-based anti-VEGF treatment, control examinations and treatment intervals were performed according to the guidelines over a mean follow-up of 2 years. In another collective of 100 eyes from 100 patients with treatment of nAMD 2 groups were observed: 1 group with patients for whom control examinations were carried out close to home including an online transmission of the results to the treating retinal center and another group in which the patients had to be examined in the treatment center. RESULTS: After 140 weeks 50 % of the patients in the first collective regularly attended control examinations and after 1 year the number was 79 %. After 2 years the probability of continuous supervision is given for only 62 % of the patients, whereas in 38 % the treatment was terminated. Of these patients treatment was terminated in 8 % due to valid criteria, whereas in 30 % of the patients the termination was unintentional. The main reason (38 %) for an unintentional termination of examination and treatment was the frequent and long journey. Patients in the second collective had a significantly higher compliance with respect to the control examinations (p < 0.001) and number of injections (p = 0.02) over the period of nearly 2 years due to the introduction of electronic transmission of images. CONCLUSION: A long-term therapy of nAMD in the clinical routine can be achieved by a close relationship with the ophthalmologist, continuous follow-up controls and therapy cycles. A close telemedical networking between the ophthalmologist and the treatment center can lead to better patient compliance. Furthermore, the construction of such platforms represents a challenge not only for the treatment of nAMD but also for other diseases. PMID- 27272635 TI - [Iritis : What has glaucoma to do with it?] PMID- 27272640 TI - Behavioral responses of three armadillo species (Mammalia: Xenarthra) to an environmental enrichment program in Villavicencio, Colombia. AB - Enrichment is a powerful tool to improve the welfare of animals under human care. Stress-related health and behavioral problems, as well as reproductive failure, are frequent in armadillos (Xenarthra, Cingulata, Dasypodidae) under human care, which hinders the development of successful ex situ conservation programs. Nevertheless, scientific studies on the effect of enrichment programs on armadillos are virtually non-existent. The objective of this study was to assess the impact of an enrichment program on the behavior of armadillos under human care. The behavior of 12 individuals of three species (Dasypus novemcinctus, D. sabanicola, and Cabassous unicinctus) maintained at Finca El Turpial, Villavicencio, Colombia, was recorded using scan sampling during three daily time blocks of 2 hr each before (4 weeks) and after (4 weeks) implementing an enrichment program. Enrichment did not stimulate the armadillos to change or extend their activity period. In general, activity levels were low during the entire study, and virtually no activity was recorded in the morning in any species, neither without nor with enrichment. The latter did, however, improve welfare by reducing abnormal and increasing natural foraging behaviors. All species were attracted by artificial termite mounds. Dasypus spp. showed special interest in cardboard boxes with food, while Cabassous was mainly attracted to hollow plastic balls filled with food. Our results suggest that separate enrichment programs need to be developed for different armadillo species, and that they should be applied during the time of day at which they are most active. Zoo Biol. 35:304-312, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272641 TI - Association of Matrix Metalloproteinase-9 (MMP9) Variants with Primary Angle Closure and Primary Angle Closure Glaucoma. AB - Shorter axial length observed in patients with primary angle closure glaucoma (PACG) might be due to altered matrix metalloproteinase-9 (MMP9) activity resulting in ECM remodeling during eye growth and development. This study aimed to evaluate common variants in MMP9 for association with PACG. Six tag SNPs of MMP9 were genotyped in a Chinese sample of 1,030 cases, including 572 PACG and 458 primary angle closure (PAC), and 499 controls. None of 6 SNPs were significantly associated with overall PAC/PACG (P > 0.07) or with PAC/PACG subgroups (Pc > 0.18). Meta-analysis of two non-Chinese studies revealed significant association between rs17576 and PACG (ORs = 0.56, P < 0.0001); however, meta-analysis of our dataset with 4 Chinese datasets did not replicate this association (ORs = 1.23, P = 0.29). Prior significant association for rs3918249 in one Caucasian study (OR = 0.63, P = 0.006) was not replicated in meta-analysis of 3 Chinese studies including this study (ORs = 0.91, P = 0.13). Significant heterogeneity between non-Chinese and Chinese datasets precluded overall meta-analysis for rs17576 and rs3918249 (Q = 0.001 and 0.04 respectively). rs17577 was nominally associated with PACG in one Caucasian study (OR = 1.71, P = 0.02), but not in 3 Chinese studies including our study (ORs = 1.20, P = 0.07). Overall meta-analysis revealed nominal association for rs17577 and PAC/PACG (ORs = 1.26, Pc = 0.05). Meta-analysis did not show significant association between the other SNPs and PAC/PACG (P > 0.47). The largest association study to date did not find significant association between MMP9 and PAC/PACG in Chinese; meta-analysis with other Chinese datasets did not produce significant association. In most instances combination with non-Chinese datasets was not possible except for one variant showing nominally significant association. More work is needed to define the role of MMP9 variants in PACG. PMID- 27272642 TI - Msa1 and Msa2 Modulate G1-Specific Transcription to Promote G1 Arrest and the Transition to Quiescence in Budding Yeast. AB - Yeast that naturally exhaust their glucose source can enter a quiescent state that is characterized by reduced cell size, and high cell density, stress tolerance and longevity. The transition to quiescence involves highly asymmetric cell divisions, dramatic reprogramming of transcription and global changes in chromatin structure and chromosome topology. Cells enter quiescence from G1 and we find that there is a positive correlation between the length of G1 and the yield of quiescent cells. The Swi4 and Swi6 transcription factors, which form the SBF transcription complex and promote the G1 to S transition in cycling cells, are also critical for the transition to quiescence. Swi6 forms a second complex with Mbp1 (MBF), which is not required for quiescence. These are the functional analogues of the E2F complexes of higher eukaryotes. Loss of the RB analogue, Whi5, and the related protein Srl3/Whi7, delays G1 arrest, but it also delays recovery from quiescence. Two MBF- and SBF-Associated proteins have been identified that have little effect on SBF or MBF activity in cycling cells. We show that these two related proteins, Msa1 and Msa2, are specifically required for the transition to quiescence. Like the E2F complexes that are quiescence specific, Msa1 and Msa2 are required to repress the transcription of many SBF target genes, including SWI4, the CLN2 cyclin and histones, specifically after glucose is exhausted from the media. They also activate transcription of many MBF target genes. msa1msa2 cells fail to G1 arrest and rapidly lose viability upon glucose exhaustion. msa1msa2 mutants that survive this transition are very large, but they attain the same thermo-tolerance and longevity of wild type quiescent cells. This indicates that Msa1 and Msa2 are required for successful transition to quiescence, but not for the maintenance of that state. PMID- 27272643 TI - Nonsuicidal self-injury among lesbian, gay, bisexual and transgender populations: an integrative review. AB - AIMS AND OBJECTIVES: To conduct an integrative review of nonsuicidal self-injury among lesbian, gay, bisexual and transgender populations to better understand the prevalence; to identify the lesbian, gay, bisexual and transgender subgroups at increased risk for nonsuicidal self-injury; and to examine the risk factors associated with nonsuicidal self-injury among lesbian, gay, bisexual and transgender populations. BACKGROUND: Nonsuicidal self-injury, defined as intentional injury to the body's surface without intent to die, is a significant mental health concern among adolescents and adults. Mental health disparities in lesbian, gay, bisexual and transgender populations, including anxiety, depression and suicidality, have been documented in the scientific literature with little focus on findings about nonsuicidal self-injury. DESIGN: Integrative literature review of published quantitative and qualitative empirical research. METHODS: A literature search of 11 on-line databases was conducted of articles published through April 2015. Keywords were used to identify articles about lesbian, gay, bisexual and transgender populations and nonsuicidal self-injury. RESULTS: After screening by title, abstract and full text, 26 articles were included in this review. The literature synthesised demonstrates a consistent pattern of increased prevalence of nonsuicidal self-injury among sexual and gender minority populations compared with heterosexual peers. This body of literature indicates which subgroups of the lesbian, gay, bisexual and transgender populations appear to be at increased risk for nonsuicidal self-injury and which specific factors contributing to vulnerability to nonsuicidal self-injury among these populations. CONCLUSIONS: Lesbian, gay, bisexual and transgender populations are at higher risk for nonsuicidal self-injury compared with the general population. Lesbian, gay, bisexual and transgender-specific and general risk factors appear to contribute to this heightened vulnerability. RELEVANCE TO CLINICAL PRACTICE: Clinical nurses should screen for nonsuicidal self-injury and for sexual and gender minority identity in all of their patients. Comprehensive assessment of lesbian, gay, bisexual and transgender patients presenting with nonsuicidal self injury may lead to identification of risk factors that can be addressed through nursing interventions. Nurse researchers and clinicians should take an active role in developing and implementing evidenced-based tailored interventions to reduce the higher vulnerability to nonsuicidal self-injury among lesbian, gay, bisexual and transgender populations. PMID- 27272645 TI - Fungal and bacterial growth in floor dust at elevated relative humidity levels. AB - Under sustained, elevated building moisture conditions, bacterial and fungal growth occurs. The goal of this study was to characterize microbial growth in floor dust at variable equilibrium relative humidity (ERH) levels. Floor dust from one home was embedded in coupons cut from a worn medium-pile nylon carpet and incubated at 50%, 80%, 85%, 90%, 95%, and 100% ERH levels. Quantitative PCR and DNA sequencing of ribosomal DNA for bacteria and fungi were used to quantify growth and community shifts. Over a 1-wk period, fungal growth occurred above 80% ERH. Growth rates at 85% and 100% ERH were 1.1 * 104 and 1.5 * 105 spore equivalents d-1 mg dust-1 , respectively. Bacterial growth occurred only at 100% ERH after 1 wk (9.0 * 104 genomes d-1 mg dust-1 ). Growth resulted in significant changes in fungal (P<.00001) and bacterial community structure (P<.00001) at varying ERH levels. Comparisons between fungal taxa incubated at different ERH levels revealed more than 100 fungal and bacterial species that were attributable to elevated ERH. Resuspension modeling indicated that more than 50% of airborne microbes could originate from the resuspension of fungi grown at ERH levels of 85% and above. PMID- 27272644 TI - Per capita increase in hospital presentations and admissions among children since the 1990s. AB - AIM: Data regarding temporal trends in per capita paediatric hospital presentations and admissions are required to inform health system and workforce planning. METHODS: Emergency Department (ED) presentations and admissions to the University Hospital Geelong among patients aged 0 to 16 years over a 12-month period (2012-2013) were determined by review of hospital records and then compared with similar data collected during 1996/1997.1 During each period, the Geelong region was serviced by a single ED, enabling us to estimate per capita presentation and admission rates. RESULTS: Since 1996/1997, per capita paediatric presentations to the ED increased from 643 to 1837 per 10 000 (186%; 95% confidence interval 181% to 191%). Moreover, the proportion of paediatric ED presentations resulting in hospital admission increased from 12.3% to 18.3% (49%; 95% confidence interval 39% to 59%). CONCLUSIONS: There has been a substantial absolute and per capita increase in paediatric ED presentations and hospital admissions since the 1990s. These trends place an increasing burden on the public hospital system, and strategies are required to promote paediatric acute care in the ambulatory setting. PMID- 27272646 TI - Cobalt-Catalyzed C(sp(2) )-H Methylation by using Dicumyl Peroxide as both the Methylating Reagent and Hydrogen Acceptor. AB - The first cobalt-catalyzed direct methylation of a C(sp(2) )-H bond using dicumyl peroxide (DCP) as both the methylating reagent and hydrogen acceptor has been established. The reaction proceeded without the use of any additives, and was proven to be applicable to various amides bearing a 2-pyridinylisopropyl (PIP) directing group, providing an efficient access to o-methyl aryl amides with high functional-group tolerance. Preliminary mechanistic studies suggest a radical process would be involved in the catalytic process. PMID- 27272647 TI - Biospectroscopy, biospectrometry and imaging of Ilex paraguariensis. Basis for non-destructive quality evaluation using artificial vision. AB - Yerba mate (YM) is massively produced and consumed as an infusion in South America and is gaining popularity all over the world. This product is obtained from the dried leaves of Ilex paraguariensis Saint Hilaire, mixed with fragments of its dried branches. For its commercialization YM must have a minimum percentage of leaves according to a standard classification. Until now, composition quantification has been mechanically performed, thus development of new methods is still pending. In this work a quantification method using solid phase molecular fluorescence, alternately diffuse reflectance spectroscopy and an imaging technique using a scanner have been proposed. Strong differences between the spectroscopic properties of leaves and sticks were observed and in all the cases linear correlations between the processed signals and composition were observed. Interesting differences in chemical composition of YM leaves and sticks were additionally obtained in this work by means of total phenol content quantification, ultraviolet matrix assisted laser-desorption ionization mass spectrometry and ultraviolet laser-desorption ionization mass spectrometry. PMID- 27272648 TI - Uses and misuses of the fudge factor in quantitative discovery proteomics. AB - Selecting proteins with significant differential abundance is the cornerstone of many relative quantitative proteomics experiments. To do so, a trade-off between p-value thresholding and fold-change thresholding can be performed because of a specific parameter, named fudge factor, and classically noted s0 . We have observed that this fudge factor is routinely turned away from its original (and statistically valid) use, leading to important distortion in the distribution of p-values, jeopardizing the protein differential analysis, as well as the subsequent biological conclusion. In this article, we provide a comprehensive viewpoint on this issue, as well as some guidelines to circumvent it. PMID- 27272649 TI - Alphabet-Inspired Design of (Hetero)Aromatic Push-Pull Chromophores. AB - Push-pull molecules represent a unique and fascinating class of organic pi conjugated materials. Herein, we provide a summary of their recent extraordinary design inspired by letters of the alphabet, especially focusing on H-, L-, T-, V , X-, and Y-shaped molecules. Representative structures from each class were presented and their fundamental properties and prospective applications were discussed. In particular, emphasis is given to molecules recently prepared in our laboratory with T-, X-, and Y-shaped arrangements based on indan-1,3-dione, benzene, pyridine, pyrazine, imidazole, and triphenylamine. These push-pull molecules turned out to be very efficient charge-transfer chromophores with tunable properties suitable for second-order nonlinear optics, two-photon absorption, reversible pH-induced and photochromic switching, photocatalysis, and intercalation. PMID- 27272650 TI - Left ventricular performance during triggered left ventricular pacing in patients with cardiac resynchronization therapy and left bundle branch block. AB - PURPOSE: To assess the acute effect of triggered left ventricular pacing (tLVp) on left ventricular performance and contraction pattern in patients with heart failure, left bundle branch block (LBBB), and cardiac resynchronization therapy (CRT). METHODS: Twenty-three patients with pre-implant QRS complex >150 ms, QRS complex narrowing under CRT, and sinus rhythm were included >=3 months after CRT implantation. Echocardiographic assessment of left ventricular ejection fraction (LVEF), global peak systolic longitudinal strain (GLS), and contraction pattern by 2D strain was performed during intrinsic conduction, tLVp, and BiV pacing and compared as paired data. Echocardiographic analysis was done blinded with respect to pacing mode. RESULTS: LVEF was significantly higher during BiV pacing (47 +/- 11 %) compared with intrinsic conduction (43 +/- 13 %, P = 0.001) and tLVp (44 +/ 13 %, P = 0.001), while there was no difference between intrinsic conduction and tLVp (P = 0.28). GLS was higher during BiV (14 +/- 3) than during intrinsic conduction (13 +/- 3, P = 0.01) and tLVp (13 +/- 3, P = 0.03). Difference in time to-peak contraction between the basal septal and lateral walls was shorter during BiV pacing (-3 +/- 44 ms) than during intrinsic conduction (129 +/- 66, P < 0.001) and tLVp (118 +/- 118 ms, P < 0.001), with no difference between tLVp and intrinsic conduction (P = 0.56). The electrocardiogram showed change in frontal axis from intrinsic conduction in only 2 (9 %) patients during tLVp and in 20 (87 %) patients during BiV pacing. CONCLUSIONS: The acute effect of tLVp on LV systolic function and contraction pattern is significantly lower than the effect of BiV pacing and not different from intrinsic conduction in patients with LBBB and CRT. PMID- 27272651 TI - Apnea-hypopnea index as a predictor of atrial fibrillation recurrence following initial pulmonary vein isolation: usefulness of type-3 portable monitor for sleep disordered breathing. AB - PURPOSE: The relationship between atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) and sleep-disordered breathing (SDB) evaluated using type-3 portable monitoring (PM) is still unknown. We investigated high-risk patients with AF recurrence after initial PVI using the apnea-hypopnea index (AHI) measured by type-3 PM. METHODS: One hundred twenty-four (85 males; age 62 +/- 10 years) AF patients undergoing initial PVI were enrolled: 83, paroxysmal AF; 41, persistent AF. At baseline, all patients were subjected to in-hospital unattended overnight polygraphy using type-3 PM for SDB. RESULTS: During 13 +/- 7 months following initial PVI, 47 patients (38 %) experienced AF recurrence. AHI and left atrial volume index (LAVI) were significantly greater in patients with than in those without AF recurrence (AHI P = 0.011; LAVI P < 0.001). LAVI was an independent predictor of AF recurrence following initial PVI in patients with both paroxysmal AF and persistent AF (paroxysmal AF P = 0.008; persistent AF P = 0.002). However, AHI was an independent predictor of AF recurrence following initial PVI in patients with paroxysmal AF (P = 0.034) but not in those with persistent AF. The optimal cutoff value was defined as AHI = 14.1. AF recurrence following PVI is three times higher in patients with AHI >=14.1 than in patients with AHI < 14.1. CONCLUSIONS: AHI measured using type-3 PM is a useful predictor of outcome following initial PVI in patients with paroxysmal AF. PMID- 27272652 TI - Pulmonary Vascular Capacitance is Associated with Vasoreactivity and Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension. AB - PURPOSE: This study aimed to identify the relationship between pulmonary vascular capacitance (PVC) and vasoreactivity in patients with idiopathic pulmonary arterial hypertension (IPAH), and the value of PVC in predicting long-term response to CCB treatment. METHODS: Pulmonary vasodilator testing with inhaling iloprost was performed in 308 newly diagnosed IPAH patients. Acute vasodilator responsive patients accepted CCBs treatment. Patients who benefit from long-term CCB were defined as those being in World Health Organization (WHO) functional class II or I after at least 1 year on CCB monotherapy. RESULTS: PVC had significant correlations with WHO function class, 6-min walk distance, mean pulmonary arterial pressure, and pulmonary vascular resistance (r = -0.363, p < 0.001; r = 0.333, p < 0.001; r = -0.514, p < 0.001; r = -0.739, p < 0.001). Thirty-five acute vasodilator-responsive IPAH patients (11.4 %) displayed less severe disease and a higher baseline PVC (1.5 +/- 0.6 vs. 1.1 +/- 0.7 ml/mmHg, p = 0.003). During acute vasodilator testing, PVC increased significantly by mean of 79 +/- 48 % and reached to a higher absolute value of 2.6 +/- 1.5 ml/mmHg compared with non-responsive patients (1.4 +/- 1.5 ml/mmHg, p < 0.001). Furthermore, PVC increased more during acute vasodilator testing in the 24 patients who benefit from long-term CCB treatment (1.4 +/- 1.3 vs. 0.5 +/- 0.4 ml/mmHg, p = 0.004). The OR of increased PVC during vasodilator testing for predicting patients with long-term response to CCB was 1.24 (95 % CI 1.02-1.50, p = 0.031) as assessed by multivariable logistic regression analysis. CONCLUSIONS: PVC was higher in acute vasodilator-responsive IPAH patients and may be a predictor of long-term response to CCBs therapy. PMID- 27272653 TI - Impact of Donor Arterial Partial Pressure of Oxygen on Outcomes After Lung Transplantation in Adult Cystic Fibrosis Recipients. AB - INTRODUCTION: Donor PaO2 levels are used for assessing organs for lung transplantation (LTx), but survival implications of PaO2 levels in adult cystic fibrosis (CF) patients receiving LTx are unclear. METHODS: UNOS registry data spanning 2005-2013 were used to test for associations of donor PaO2 with patient survival and bronchiolitis obliterans syndrome (BOS) in adult (age >= 18 years) first-time LTx recipients diagnosed with CF. RESULTS: The analysis included 1587 patients, of whom 1420 had complete data for multivariable Cox models. No statistically significant differences among donor PaO2 categories of <=200, 201 300, 301-400, or >400 mmHg were found in univariate survival analysis (log-rank test p = 0.290). BOS onset did not significantly differ across donor PaO2 categories (Chi-square p = 0.480). Multivariable Cox models of patient survival supported the lack of difference across donor PaO2 categories. Interaction analysis found a modest difference in survival between the two top categories of donor PaO2 when examining patients with body mass index (BMI) in the lowest decile (<=16.5 kg/m(2)). CONCLUSIONS: Donor PaO2 was not associated with survival or BOS onset in adult CF patients undergoing LTx. Notwithstanding statistically significant interactions between donor PaO2 and BMI, there was no evidence of post-LTx survival risk associated with donor PaO2 below conventional thresholds in any subgroup of adults with CF. PMID- 27272655 TI - Exercise-induced haemoptysis as a rare presentation of a rare lung disease. AB - Amyloid primarily affecting the lungs is a seldom seen clinical entity. This case discusses the work-up of a patient presenting with exercise-induced haemoptysis and diffuse cystic lung disease on radiographic imaging. The common clinical and radiographic findings of diffuse cystic lung diseases as well as a brief overview of pulmonary amyloid are presented. PMID- 27272656 TI - The Mechanism of Phosphonium Ylide Alcoholysis and Hydrolysis: Concerted Addition of the O-H Bond Across the P=C Bond. AB - The previous work on the hydrolysis and alcoholysis reactions of phosphonium ylides is summarized and reviewed in the context of their currently accepted mechanisms. Several experimental facts relating to ylide hydrolysis and to salt and ylide alcoholysis are shown to conflict with those mechanisms. In particular, we demonstrate that the pKa values of water and alcohols are too high in organic media to bring about protonation of ylide. Therefore, we propose concerted addition of the water or alcohol O-H bond across the ylide P=C bond. In support of this, we provide NMR spectroscopic evidence for equilibrium between ylide and aclohol that does not require the involvement of phosphonium hydroxide. We report the first P-alkoxyphosphorane to be characterised by NMR spectroscopy that does not undergo exchange on an NMR timescale. Two-dimensional NMR spectroscopic techniques have been applied to the characterisation to P-alkoxyphosphoranes for the first time. PMID- 27272654 TI - Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. AB - Age is a significant risk factor for the development of cancer. However, the mechanisms that drive age-related increases in cancer remain poorly understood. To determine if senescent stromal cells influence tumorigenesis, we develop a mouse model that mimics the aged skin microenvironment. Using this model, here we find that senescent stromal cells are sufficient to drive localized increases in suppressive myeloid cells that contributed to tumour promotion. Further, we find that the stromal-derived senescence-associated secretory phenotype factor interleukin-6 orchestrates both increases in suppressive myeloid cells and their ability to inhibit anti-tumour T-cell responses. Significantly, in aged, cancer free individuals, we find similar increases in immune cells that also localize near senescent stromal cells. This work provides evidence that the accumulation of senescent stromal cells is sufficient to establish a tumour-permissive, chronic inflammatory microenvironment that can shelter incipient tumour cells, thus allowing them to proliferate and progress unabated by the immune system. PMID- 27272657 TI - Multiplex Relationships and HIV: Implications for Network-Based Interventions. AB - The number of network members and the roles they play can influence risk behaviors and consequently intervention strategies to reduce HIV transmission. We recruited 652 people who use drugs (PWUD) from socially disadvantaged neighborhoods in New York City (07/2006-06/2009). Interviewer-administered surveys ascertained demographic, behavioral, and network data. We used logistic regression, stratified by exchange sex, to assess the relationship between HIV status and the number of network members with different roles, treated as independent and multiplex (i.e., drug + sex). Those with more multiplex risk ties were significantly more likely to be HIV positive, but only among those not reporting exchange sex (AOR = 3.2). Among those reporting exchange sex, men reporting recent male sex partners were more likely to report HIV positive status (AOR = 12.6). These data suggest that sex and drug relationships among PWUD are interrelated. Interventions that target multiplex rather than single-role relationships may be more effective in influencing behavior change. PMID- 27272658 TI - [Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial]. PMID- 27272659 TI - [Clinical Evaluation of Proton Therapy - How much benefit can be considered a benefit?]. PMID- 27272660 TI - Risk of biochemical recurrence and timing of radiotherapy in pT3a N0 prostate cancer with positive surgical margin : A single center experience. AB - BACKGROUND: Despite improved biochemical recurrence-free survival rates by the use of immediate adjuvant radiotherapy (RT) in patients with locally advanced prostate cancer, disagreement about the need and timing of RT remains. PATIENTS AND METHODS: From 2005-2009, 94 patients presenting with a stage pT3a N0 and microscopic positive resection margin were retrospectively analyzed after radical prostatectomy. Special attention was given to patients' outcome, the frequency of additive RT, and its efficacy. RESULTS: Median follow-up was 80 months. A total of 71 patients had a negative postoperative prostate-specific antigen (PSA) level (<0.07 ng/ml). Thirty-six of them did not experience any PSA relapse (subgroup 1). Fourteen of them received additive RT and during follow-up all 36 patients remained PSA negative. Of 71 initially PSA-negative patients, 35 had a biochemical relapse (subgroup 2); 28 patients underwent salvage RT. The median PSA value before salvage RT was 0.24 ng/ml and was subsequently negative (<0.07 ng/ml) in 23 patients after RT. Of the entire cohort, 23 patients had persisting PSA after surgery (subgroup 3). Of these, 18 patients received salvage RT at a median PSA level of 0.4 ng/ml. One patient in subgroup 1, 5 patients in subgroup 2, and 9 patients in subgroup 3 had ongoing androgen deprivation therapy. CONCLUSION: The present study of 94 pT3a N0 R1 prostate cancer patients provides insight into medical care of this patient cohort and underlines the need for additive RT for the majority of patients to achieve long-term biochemical control. Although immediate adjuvant RT was applied with restraint (20 %), during the observation period 60 of 94 patients (63.8 %) received RT - highlighting the need of postoperative treatment. PMID- 27272661 TI - Neoadjuvant chemoradiotherapy of rectal carcinoma : Baseline hematologic parameters influencing outcomes. AB - BACKGROUND: The link between the blood count and a systemic inflammatory response (SIR) is indisputable and well described. Pretreatment hematological parameters may predict the overall clinical outcomes in many types of cancer. Thus, this study aims to systematically evaluate the relationship between baseline blood count levels and treatment response in rectal cancer patients treated with neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: From 2009-2015, 173 patients with locally advanced rectal cancer were retrospectively enrolled in the study and analyzed. The baseline blood count was recorded in all patients 1 week before chemoradiation. Tumor response was evaluated through pathologic findings. Blood count levels which included RBC (red blood cells), Hb (hemoglobin), PLT (platelet count), neutrophil count, WBC (white blood cells), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) were analyzed in relation to tumor downstaging, pCR (pathologic complete response), OS (overall survival), and DFS (disease-free survival). RESULTS: Hb levels were associated with a response in logistic regression analysis: pCR (p = 0.05; OR 1.04, 95 % CI 1.00-1.07); T downstaging (p = 0.006; OR 1.03, 95 % CI 1.01-1.05); N downstaging (p = 0.09; OR 1.02, 95 % CI 1.00-1.04); T or N downstaging (p = 0.007; OR 1.04, 95 % CI 1.01 1.07); T and N downstaging (p = 0.02; OR 1.02, 95 % CI 1.00-1.04); Hb and RBC were the most significant parameters influencing OS; PLT was a negative prognostic factor for OS and DFS (p = 0.008 for OS); an NLR value of 2.8 was associated with the greatest significance for OS (p = 0.03) and primary tumor downstaging (p = 0.02). CONCLUSION: Knowledge of pretreatment hematological parameters appears to be an important prognostic factor in patients with rectal carcinoma. PMID- 27272662 TI - Effects of metal and predator stressors in larval southern toads (Anaxyrus terrestris). AB - Natural and anthropogenic stressors typically do not occur in isolation; therefore, understanding ecological risk of contaminant exposure should account for potential interactions of multiple stressors. Realistically, common contaminants can also occur chronically in the environment. Because parental exposure to stressors may cause transgenerational effects on offspring, affecting their ability to cope with the same or novel environmental stressors, the exposure histories of generations preceding that being tested should be considered. To examine multiple stressor and parental exposure effects we employed a 2 * 2 * 2 factorial design in outdoor 1000-L mesocosms (n = 24). Larval southern toads (Anaxyrus terrestris), bred from parents collected from reference and metal-contaminated sites, were exposed to two levels of both an anthropogenic (copper-0, 30 ug/L Cu) and natural (predator cue - present/absent) stressor and reared to metamorphosis. Toads from the metal-contaminated parental source population were smaller at metamorphosis and had delayed development; i.e., a prolonged larval period. Similarly, larval Cu exposure also reduced size at metamorphosis and prolonged the larval period. We, additionally, observed a significant interaction between larval Cu and predator-cue exposure on larval period, wherein delayed emergence was only present in the 30-ug/L Cu treatments in the absence of predator cues. The presence of parental effects as well as an interaction between aquatic stressors on commonly measured endpoints highlight the importance of conducting multistressor studies across generations to obtain data that are more relevant to field conditions in order to determine population level effects of contaminant exposure. PMID- 27272663 TI - Nondestructive measurement of esophageal biaxial mechanical properties utilizing sonometry. AB - Malignant esophageal pathology typically requires resection of the esophagus and reconstruction to restore foregut continuity. Reconstruction options are limited and morbid. The esophagus represents a useful target for tissue engineering strategies based on relative simplicity in comparison to other organs. The ideal tissue engineered conduit would have sufficient and ideally matched mechanical tolerances to native esophageal tissue. Current methods for mechanical testing of esophageal tissues both in vivo and ex vivo are typically destructive, alter tissue conformation, ignore anisotropy, or are not able to be performed in fluid media. The aim of this study was to investigate biomechanical properties of swine esophageal tissues through nondestructive testing utilizing sonometry ex vivo. This method allows for biomechanical determination of tissue properties, particularly longitudinal and circumferential moduli and strain energy functions. The relative contribution of mucosal-submucosal layers and muscular layers are compared to composite esophagi. Swine thoracic esophageal tissues (n = 15) were tested by pressure loading using a continuous pressure pump system to generate stress. Preconditioning of tissue was performed by pressure loading with the pump system and pre-straining the tissue to in vivo length before data was recorded. Sonometry using piezocrystals was utilized to determine longitudinal and circumferential strain on five composite esophagi. Similarly, five mucosa submucosal and five muscular layers from thoracic esophagi were tested independently. This work on esophageal tissues is consistent with reported uniaxial and biaxial mechanical testing and reported results using strain energy theory and also provides high resolution displacements, preserves native architectural structure and allows assessment of biomechanical properties in fluid media. This method may be of use to characterize mechanical properties of tissue engineered esophageal constructs. PMID- 27272664 TI - Parent-Adolescent Conflict in African American Families. AB - Parent-adolescent conflict is frequent in families and has implications for youth adjustment and family relationships. Drawing on a family systems perspective, we examined mothers', fathers', and two adolescent-aged siblings' (50.5 % females) reports of parent-adolescent conflict in 187 African American families. Using latent profile analysis in the context of an ethnic homogeneous design, we identified three family types based on levels of and differences between parent and youth conflict reports: low conflict, father high conflict, and younger sibling high conflict. Compared to low conflict families, youth in younger sibling high conflict families reported more depressive symptoms and risky behaviors. The results for parents' acceptance revealed that, in comparison to low conflict families, older siblings in father high conflict families reported lower acceptance from mothers, and mothers in these families reported lower acceptance of their children; further, older siblings in younger sibling high conflict families reported less acceptance from fathers, and fathers in these families reported less acceptance of their children. Results underscore the significance of levels of and both differences between and direction of differences in parents' and youth's reports of their "shared" experiences, as well as the importance of examining the larger family contexts of dyadic parent relationships. PMID- 27272665 TI - MRSA Causing Infections in Hospitals in Greater Metropolitan New York: Major Shift in the Dominant Clonal Type between 1996 and 2014. AB - A surveillance study in 1996 identified the USA100 clone (ST5/SCCmecII)-also known as the "New York/Japan" clone-as the most prevalent MRSA causing infections in 12 New York City hospitals. Here we update the epidemiology of MRSA in seven of the same hospitals eighteen years later in 2013/14. Most of the current MRSA isolates (78 of 121) belonged to the MRSA clone USA300 (CC8/SCCmecIV) but the USA100 clone-dominant in the 1996 survey-still remained the second most frequent MRSA (25 of the 121 isolates) causing 32% of blood stream infections. The USA300 clone was most common in skin and soft tissue infections (SSTIs) and was associated with 84.5% of SSTIs compared to 5% caused by the USA100 clone. Our data indicate that by 2013/14, the USA300 clone replaced the New York/Japan clone as the most frequent cause of MRSA infections in hospitals in Metropolitan New York. In parallel with this shift in the clonal type of MRSA, there was also a striking change in the types of MRSA infections from 1996 to 2014. PMID- 27272666 TI - Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement: A Systematic Review and Meta-analysis. AB - BACKGROUND: The comparative benefits and harms of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for patients with aortic stenosis are unclear. PURPOSE: To compare clinical outcomes, including early (<=30-day) and midterm (<=1-year) mortality, in adults with severe aortic stenosis undergoing either TAVI or SAVR. DATA SOURCES: MEDLINE, Cochrane, and Scopus databases (without language restrictions) from April 2002 to 5 April 2016; multiple registries and Web sites; scientific meeting presentations. STUDY SELECTION: Five randomized trials and 31 observational matched studies comparing mortality outcomes after TAVI or SAVR. DATA EXTRACTION: Two investigators independently extracted study data and rated risk of bias. DATA SYNTHESIS: 16 638 patients were analyzed. Overall, there was no statistically significant difference between TAVI and SAVR in early (odds ratio [OR], 1.01 [95% CI, 0.81 to 1.26]) or midterm (OR, 0.96 [CI, 0.81 to 1.14]) all-cause mortality. Analyses restricted to trials (early: OR, 0.80 [CI, 0.51 to 1.25]; midterm: OR, 0.90 [CI, 0.64 to 1.26]) were inconclusive, with wide CIs, whereas analyses of matched studies were similar to the overall results. Transfemoral TAVI provided mortality benefits over SAVR in trials. Analyses restricted to studies of patients at low to intermediate risk showed statistically nonsignificant reductions in early (OR, 0.67 [CI, 0.42 to 1.07]) and midterm (OR, 0.91 [CI, 0.67 to 1.23]) mortality with TAVI. Incidence of periprocedural myocardial infarction, major bleeding, acute kidney injury, and new-onset atrial fibrillation was lower with TAVI, but risk for pacemaker implantation, vascular complications, and paravalvular leak increased. Overall, there was a statistically nonsignificant increased risk in long-term (2- to 5-year) all-cause mortality with TAVI (OR, 1.28 [CI, 0.97 to 1.69]), whereas long-term mortality outcomes in patients at low to intermediate risk were inconclusive, with wide CIs (OR, 1.06 [CI, 0.59 to 1.91]). LIMITATION: The number of trials was limited, and study designs and patient characteristics were heterogeneous. CONCLUSION: Compared with SAVR, TAVI may have similar or better early and midterm outcomes for adults with aortic stenosis, including those at low to intermediate risk. PRIMARY FUNDING SOURCE: None. PMID- 27272667 TI - Influence of Liver Disease on Perioperative Outcome After Bariatric Surgery in a Northern German Cohort. AB - OBJECTIVES: The aim of this study was to assess the prevalence of non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients and evaluate the influence on perioperative complications. BACKGROUND: Patients undergoing bariatric surgery have a high incidence of non-alcoholic steatohepatitis (NASH). Upcoming data indicates that liver disease has a significant effect on perioperative complications. However, the influence of NAFLD/NASH on perioperative outcome in bariatric patients is still controversial. METHODS: We identified a total of 302 patients with concomitant liver biopsies, while performing either laparoscopic Roux-Y gastric bypass or sleeve gastrectomy. Liver biopsy was performed in case of abnormal liver appearance at time of bariatric surgery. Histological results were compared to perioperative complication rate. RESULTS: NAFLD is common in our patient cohort. Abnormal findings in liver histology were found in 82.3 % of our patients. Liver cirrhosis was newly diagnosed in 12 patients (4 %). There were no complications due to liver biopsy. The mortality rate was 0.3 %, leakage rate was 1 %, and postoperative bleeding occurred in 3.3 %. Pulmonary complications were observed in 1.7 % and cardiovascular complications in 1.3 %. One patient developed portal vein thrombosis and one patient acute pancreatitis; both were treated conservatively. No patient had postoperative liver failure. We found no association between histological findings and perioperative outcomes. CONCLUSIONS: The prevalence of NAFLD among morbidly obese surgical patients was high, although this condition was not associated with increased risk for postoperative complications. Because of unexpected findings in intraoperative liver biopsies, the routine indication of liver biopsies in patients at high risk for liver disease should be discussed. PMID- 27272668 TI - Re-operations after Secondary Bariatric Surgery: a Systematic Review. AB - This paper reviews reoperations rates for short- and long-term complications following secondary bariatric procedures and need for further bariatric surgery. The search revealed 28 papers (1317 secondary cases) following at least 75 % of patients for 12 months or more. For adjustable gastric banding (AGB), rebanding had higher re-revisional rates than conversions into other procedures. Conversion of AGB to Roux-en-Y gastric bypass had the highest number of short- (10.7 %) and long-term (22.0 %) complications. We estimated 194 additional reoperations per 1000 patients having a secondary procedure, 8.8 % needing tertiary surgery. Despite being poorly reported, risks of reoperations for long-term complications and tertiary bariatric surgery are higher than usually reported risks of short term complications and should be taken into account when choosing a secondary bariatric procedure and for economic evaluations. PMID- 27272669 TI - Phenotypic plasticity of mate recognition systems prevents sexual interference between two sympatric leaf beetle species. AB - Maladaptive sexual interactions among heterospecific individuals (sexual interference) can prevent the coexistence of animal species. Thus, the avoidance of sexual interference by divergence of mate recognition systems is crucial for a stable coexistence in sympatry. Mate recognition systems are thought to be under tight genetic control. However, we demonstrate that mate recognition systems of two closely related sympatric leaf beetle species show a high level of host induced phenotypic plasticity. Mate choice in the mustard leaf beetles, Phaedon cochleariae and P. armoraciae, is mediated by cuticular hydrocarbons (CHCs). Divergent host plant use causes a divergence of CHC phenotypes, whereas similar host use leads to their convergence. Consequently, both species exhibit significant behavioral isolation when they feed on alternative host species, but mate randomly when using a common host. Thus, sexual interference between these syntopic leaf beetles is prevented by host-induced phenotypic plasticity rather than by genotypic divergence of mate recognition systems. PMID- 27272671 TI - Electronically Mediated Time-out Initiative to Reduce the Incidence of Wrong Surgery: An Interventional Observational Study. AB - BACKGROUND: "Wrong surgery" is defined as wrong site, wrong operation, or wrong patient, with estimated incidence up to 1 per 5,000 cases. Responding to national attention on wrong surgery, our objective was to create a care redesign intervention to minimize the rate of wrong surgery. METHODS: The authors created an electronic system using existing intraoperative electronic documentation to present a time-out checklist on large in-room displays. Time-out was dynamically interposed as a forced-function documentation step between "patient-in-operating room" and "incision." Time to complete documentation was obtained from audit logs. The authors measured the postimplementation wrong surgery rate and used Bayesian methods to compare the pre- and postimplementation rates at our institution. Previous probabilities were selected using wrong surgery rate estimates from the observed performance reported in the literature to generate previous probabilities (4.24 wrong surgeries per 100,000 cases). RESULTS: No documentation times exceeded 5 min; 97% of documentation tasks were completed within 2 min. The authors performed 243,939 operations over 5 yr using the system, with zero wrong surgeries, compared with 253,838 operations over 6 yr with two wrong surgeries before implementation. Bayesian analysis suggests an 84% probability that the postimplementation wrong rate is lower than baseline. However, given the rarity of wrong surgery in our sample, there is substantial uncertainty. The total system-development cost was $34,000, roughly half the published cost of one weighted median settlement for wrong surgery. CONCLUSION: Implementation of a forced-completion electronically mediated time-out process before incision is feasible, but it is unclear whether true performance improvements occur. PMID- 27272672 TI - Intrathecal Catheterization and Drug Delivery in Guinea Pigs: A Small-animal Model for Morphine-evoked Granuloma Formation. AB - BACKGROUND: Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs. METHODS: Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel. RESULTS: (1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 MUg/10 MUl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene > polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 MUl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies. CONCLUSIONS: Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular. PMID- 27272673 TI - Rapid Infusion of Hydroxyethyl Starch 70/0.5 but not Acetate Ringer's Solution Decreases the Plasma Concentration of Propofol during Target-controlled Infusion. AB - BACKGROUND: Rapid fluid infusion resulting in increased hepatic blood flow may decrease the propofol plasma concentration (Cp) because propofol is a high hepatic extraction drug. The authors investigated the effects of rapid colloid and crystalloid infusions on the propofol Cp during target-controlled infusion. METHODS: Thirty-six patients were randomly assigned to 1 of 3 interventions (12 patients per group). At least 30 min after the start of propofol infusion, patients received either a 6% hydroxyethyl starch (HES) solution at 24 ml.kg.h or acetated Ringer's solution at 24 or 2 ml.kg.h during the first 20 min. In all groups, acetated Ringer's solution was infused at 2 ml.kg.h during the next 20 min. The propofol Cp was measured every 2.5 min as the primary outcome. Cardiac output, blood volume, and indocyanine green disappearance rate were determined using a pulse dye densitogram analyzer before and after the start of fluid administration. Effective hepatic blood flow was calculated as the blood volume multiplied by the indocyanine green disappearance rate. RESULTS: The rapid HES infusion significantly decreased the propofol Cp by 22 to 37%, compared to the Cp at 0 min, whereas the rapid or maintenance infusion of acetate Ringer's solution did not decrease the propofol Cp. Rapid HES infusion, but not acetate Ringer's solution infusion, increased the effective hepatic blood flow. CONCLUSIONS: Rapid HES infusion increased the effective hepatic blood flow, resulting in a decreased propofol Cp during target-controlled infusion. Rapid HES infusion should be used cautiously as it may decrease the depth of anesthesia. PMID- 27272674 TI - Changes in Brain Resting-state Functional Connectivity Associated with Peripheral Nerve Block: A Pilot Study. AB - BACKGROUND: Limited information exists on the effects of temporary functional deafferentation (TFD) on brain activity after peripheral nerve block (PNB) in healthy humans. Increasingly, resting-state functional connectivity (RSFC) is being used to study brain activity and organization. The purpose of this study was to test the hypothesis that TFD through PNB will influence changes in RSFC plasticity in central sensorimotor functional brain networks in healthy human participants. METHODS: The authors achieved TFD using a supraclavicular PNB model with 10 healthy human participants undergoing functional connectivity magnetic resonance imaging before PNB, during active PNB, and during PNB recovery. RSFC differences among study conditions were determined by multiple-comparison corrected (false discovery rate-corrected P value less than 0.05) random-effects, between-condition, and seed-to-voxel analyses using the left and right manual motor regions. RESULTS: The results of this pilot study demonstrated disruption of interhemispheric left-to-right manual motor region RSFC (e.g., mean Fisher transformed z [effect size] at pre-PNB 1.05 vs. 0.55 during PNB) but preservation of intrahemispheric RSFC of these regions during PNB. Additionally, there was increased RSFC between the left motor region of interest (PNB-affected area) and bilateral higher order visual cortex regions after clinical PNB resolution (e.g., Fisher z between left motor region of interest and right and left lingual gyrus regions during PNB, -0.1 and -0.6 vs. 0.22 and 0.18 after PNB resolution, respectively). CONCLUSIONS: This pilot study provides evidence that PNB has features consistent with other models of deafferentation, making it a potentially useful approach to investigate brain plasticity. The findings provide insight into RSFC of sensorimotor functional brain networks during PNB and PNB recovery and support modulation of the sensory-motor integration feedback loop as a mechanism for explaining the behavioral correlates of peripherally induced TFD through PNB. PMID- 27272675 TI - Relationship between Estimated Glomerular Filtration Rate and Cardiovascular Mortality in a Japanese Cohort with Long-Term Follow-Up. AB - BACKGROUND: Patients with renal impairment are at risk of not only end-stage kidney disease but also cardiovascular disease (CVD). The current definition of CKD stage G3a is eGFR 45-59 ml/min/1.73 m2 and of G3b is 30-44 ml/min/1.73 m2, and subjects in the CKD 3a category are considered to be at lower risk of mortality than are those in CKD 3b. METHODS: We evaluated the outcome of 97,043 people (33,131 men and 63,912 women) living in Ibaraki Prefecture who underwent annual community-based health checkups beginning in 1993 at age 40-80 years and who were followed for a mean of 17.1 years. RESULTS: The number of all-causes deaths was 20,534 (10,375 men and 10,159 women), of which 5,995 (2,695 men and 3,300 women) were deaths due to CVD. Multivariable-adjusted hazard ratio for CVD death in the eGFR 45-49 ml/min/1.73 m2 category was significantly increased (1.82; 95% confidential interval, 1.23-2.69) in non-elderly men, whereas all cause mortality and CVD mortality in elderly men with eGFR 45-49 ml/min/1.73m2 were non significant. In contrast, both in non-elderly women and in elderly women with eGFR 45-49 ml/min/1.73 m2 showed small, but significant, increases in the risks of all-cause mortality and CVD. CONCLUSIONS: We demonstrated proportionate increases in mortality with decreasing eGFR in a Japanese CKD population. Like patients in the CKD G3b subgroup, non-elderly men and women with an eGFR of 45-49 ml/min/1.73 m2 (i.e. a part of CKD G3a) are at considerable risk of CVD mortality. Age dependent and eGFR dependent finer risk recognition were required for CVD prevention in clinical practice with regard to CKD patients. PMID- 27272677 TI - The German ECMO inflation: when things other than health and care begin to rule medicine. PMID- 27272676 TI - Effects of photobiomodulation therapy (PBMT) on bovine sperm function. AB - Fertilization rates and subsequent embryo development rely on sperm factors related to semen quality and viability. Photobiomodulation therapy (PBMT) is based on emission of electromagnetic waves of a laser optical system that interact with cells and tissues resulting in biological effects. This interaction is mediated by photoacceptors that absorb the electromagnetic energy. Effects are dependent of irradiation parameters, target cell type, and species. In sperm, PBMT improves several features like motility and viability, affecting sperm aerobic metabolism and energy production. The aim of this study was to investigate, under same conditions, how different output powers (5, 7.5, and 10 mW) and time of irradiation (5 and 10 min) of laser (He-Ne laser, 633 nm) may affect frozen/thawed bovine sperm functions. Results showed significant effects depending on power while using 10 min of irradiation on motility parameters and mitochondrial potential. However, no effect was observed using 5 min of irradiation, regardless of power applied. In conclusion, PBMT is effective to modulate bovine sperm function. The effectiveness is dependent on the interaction between power applied and duration of irradiation, showing that these two parameters simultaneously influence sperm function. In this context, when using the same fluency and energy with different combinations of power and time of exposure, we observed distinct effects, revealing that biological effects should be also based on simple parameters rather than only composite parameters such as fluency, irradiance and energy. Laser irradiation of frozen/thawed bovine semen led to an increase on mitochondrial function and motility parameters that could potentially improve fertility rates. PMID- 27272678 TI - Fast 180 degrees magnetization switching in a strain-mediated multiferroic heterostructure driven by a voltage. AB - Voltage-driven 180 degrees magnetization switching provides a low-power alternative to current-driven magnetization switching widely used in spintronic devices. Here we computationally demonstrate a promising route to achieve voltage driven in-plane 180 degrees magnetization switching in a strain-mediated multiferroic heterostructure (e.g., a heterostructure consisting of an amorphous, slightly elliptical Co40Fe40B20 nanomagnet on top of a Pb(Zr,Ti)O3 film as an example). This 180 degrees switching follows a unique precessional path all in the film plane, and is enabled by manipulating magnetization dynamics with fast, local piezostrains (rise/release time <0.1 ns) on the Pb(Zr,Ti)O3 film surface. Our analyses predict ultralow area energy consumption per switching (~0.03 J/m(2)), approximately three orders of magnitude smaller than that dissipated by current-driven magnetization switching. A fast overall switching time of about 2.3 ns is also demonstrated. Further reduction of energy consumption and switching time can be achieved by optimizing the structure and material selection. The present design provides an additional viable route to realizing low-power and high-speed spintronics. PMID- 27272679 TI - Significance of duon mutations in cancer genomes. AB - Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed "duon mutations" due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures. PMID- 27272680 TI - Chronic Pelvic Inflammation Diminished Ovarian Reserve as Indicated by Serum Anti Mulerrian Hormone. AB - OBJECTIVE: To explore the potential damaging effect of chronic pelvic inflammation on ovarian reserve. DESIGN: Case-control study. PATIENTS: A total of 122 women with bilateral tubal occlusion, diagnosed by hysterosalipingography (HSG) and 217 women with normal fallopians were recruited. MEASUREMENTS: Serum anti-Mullerian hormone (AMH), basic follicle-stimulating hormone (FSH), luteining hormone (LH), estradiol (E2), and testosterone (T) were measured; and antral follicle counts (AFCs) were recorded. RESULTS: Significantly lower level of AMH was observed in women with bilateral tubal occlusion compared to control group [2.62 (2.95) ng/ml vs. 3.37 (3.11) ng/ml, P = 0.03], and the difference remained after adjustment of BMI (Padjust = 0.04). However, no statistical difference was found in the levels of FSH [7.00 (2.16) IU/L vs. 6.74 (2.30) IU/L], LH [4.18 (1.52) IU/L vs. 4.63 (2.52) IU/L], E2 [35.95 (20.40) pg/ml vs. 34.90 (17.85) pg/ml], T [25.07+/-11.46 ng/dl vs. 24.84+/-12.75 ng/dl], and AFC [6.00 (4.00) vs. 7.00 (4.00)] between two groups (p>0.05). CONCLUSIONS: Women with bilateral tubal occlusion showed decreased AMH level, suggesting that chronic pelvic inflammation may diminish ovarian reserve. More caution should be paid when evaluating the detriment of PID on female fertility. PMID- 27272681 TI - Socio-Behavioral Factors Associated with Overweight and Central Obesity in Tehranian Adults: a Structural Equation Model. AB - PURPOSE: This study aimed to test a conceptual model of associations between socio-demographic and behavioral factors and obesity in the Tehran Lipid and Glucose Study (TLGS). METHODS: Data from 2747 TLGS adult participants (58.3 % female) were analyzed. Socio-demographic and behavioral factors in the conceptual model were tested for their direct and indirect associations with overweight and central obesity, using structural equation modeling (SEM), conducted by IBM SPSS AMOS software. RESULTS: Overweight and central obesity were found in 61.6 and 48.1 % of respondents, respectively. Fit indices were acceptable for the conceptual model. Daily energy intake had a direct association with overweight and central obesity in both genders; however, poor dietary pattern had direct associations with overweight and central obesity only in men. In women, age, marital status, and level of education had direct associations with overweight and central obesity. In men, only age and marital status had direct associations with overweight and central obesity. CONCLUSIONS: Age and marital status in both genders and level of education only in women were among the socio-demographic factors which were directly associated with both overweight and central obesity. Among behavioral factors, daily energy intake was the most important factor that was directly associated with both overweight and central obesity in both genders. Adherence to poor diet directly was associated with overweight and central obesity only in men. The current findings provide beneficial information for designing culturally relevant and effective interventions/strategies for prevention of overweight among Tehranian adults. PMID- 27272682 TI - Pancreatic surgery in Italy. Criteria to identify the hospital units and the tertiary referral centers entitled to perform it. AB - Indicators of effectiveness and quality of care are urgently needed to improve the surgical outcomes. This is particularly felt in the field of complex surgical fields, such as the HPB one. International and national studies have documented an association between the large number of pancreatic surgical procedures and the outcome quality. The aim of this paper is to suggest reliable structural requirements and surgical volume to support pancreatic surgical accreditation, preserving patient's safety. Moreover, an accreditation program is outlined. PMID- 27272683 TI - Well-Differentiated Liposarcoma With Hibernoma-Like Morphology. AB - Well-differentiated liposarcoma (WDL) can show a morphologic spectrum, including lipoma-like, sclerosing and inflammatory subtypes. It does not metastasize but can dedifferentiate, acquiring metastatic potential. Hibernomas are benign neoplasms that show variable differentiation toward brown fat, and can sometimes occur in the abdomen or retroperitoneum. We illustrate a case of retroperitoneal WDL that showed extensive hibernoma-like morphology, with sheets of multivacuolated adipocytes of varying sizes, with abundant cytoplasm and numerous lipid vacuoles or granular eosinophilic cytoplasm. However, very focally there were fibrous septa containing spindle cells with enlarged, hyperchromatic, mildly pleomorphic nuclei. Further sampling showed areas of typical WDL, with lobules of mature fat intersected by fibrous septa containing atypical, enlarged spindle cells, as well as small foci of dedifferentiation. Immunohistochemistry for CDK4 and p16 showed strong and diffuse nuclear expression in the hibernoma-like areas, and fluorescence in situ hybridization showed MDM2 gene amplification, all in keeping with WDL. We highlight hibernoma-like morphology as part of the histologic spectrum of WDL, and recognition of this variant is important for correct treatment and prognostication. PMID- 27272684 TI - Molecular epidemiology and clinical severity of Human Bocavirus (HBoV) 1-4 in children with acute gastroenteritis from Pune, Western India. AB - Although acute gastroenteritis is a major public health problem worldwide, ~40% of the cases remain undiagnosed for any etiological agent. Human Bocavirus (HBoV) has been detected frequently in feces of diarrhoeic children suggesting its possible etiological involvement in the disease. HBoV has not been reported in association with acute gastroenteritis from India. Fecal samples (n = 418) collected from children (age <=5 years) hospitalized with acute gastroenteritis, between January 2009 and December 2011, from three local hospitals were examined for presence of HBoV using PCR targeting the partial VP1/VP2 capsid region (~575 bp) followed by phylogenetic analysis. HBoV was detected in 24/418 (5.7%) cases. Co-infection was observed in 5/24 (21%) cases. HBoV infections occurred in children <=12 months of age. Peak HBoV activity was observed in monsoon and post monsoon season. All four HBoV genotypes were detected in the study region. Major clinical symptoms of HBoV mono infections included diarrhoea (100%), fever (90%), dehydration (74%), and vomiting (58%). Dehydration was observed in all of the HBoV2-4 cases and in 50% of the HBoV1 cases. Clinical severity varied with genotype (HBoV2 > HBoV1 > HBoV3 > HBoV4). HBoV2 cases recorded severe and very severe infections. The study illustrates prevalence and vast genetic diversity of HBoVs in acute gastroenteritis. It highlights the clinical features of HBoV1-4 infections and sheds light on clinical impact of HBoV genotypes in gastroenteritis. J. Med. Virol. 89:17-23, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27272686 TI - [Not Available]. PMID- 27272685 TI - Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. AB - PURPOSE: Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. MATERIALS AND METHODS: 15 patients with locally advanced inoperable pancreatic cancer and tumor related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. RESULTS: Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). CONCLUSION: US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor associated pain in patients with locally advanced pancreatic cancer. KEY POINTS: * US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.* HIFU can be used for tumor volume reduction.* Using HIFU, a significant reduction of cancer-related pain was achieved.* HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: * Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Rontgenstr 2016; 188: 662 - 670. PMID- 27272687 TI - [Not Available]. PMID- 27272688 TI - Amniotic Fluid-Soluble Form of Triggering Receptors Expressed on Myeloid Cells: A Physiologic Constituent at Term. AB - BACKGROUND: Triggering receptors expressed on myeloid cells-1 (TREM-1) are innate immune receptors that mediate inflammatory response. In recent times, the role of these receptors has become the focus of several studies in the gestational context. Evaluation of soluble TREM-1 concentration in normal pregnancy is scarce, and no data are available on the levels of this receptor in the last weeks of normal pregnancy. METHOD: Amniotic fluid (AF) samples were obtained from 77 patients in the last weeks of normal pregnancy during cesarean section, and the soluble form of TREM-1 (sTREM-1) levels determined using specific sandwich enzyme-linked immunosorbent assay kit. RESULTS: sTREM-1 was detectable in all AF samples, and its levels did not vary in the last weeks of third trimester pregnancy. There was no correlation between sTREM-1 levels in AF and advancing gestational age. CONCLUSION: sTREM-1 is a physiologic constituent of AF and its levels are not temporally regulated in pregnancies at term. PMID- 27272690 TI - Age-related oscillatory theta modulation of multisensory integration in frontocentral regions. AB - This study used electroencephalogram measurements to investigate the effects of aging on oscillatory theta modulation during an audiovisual discrimination task. By a wavelet-based time-frequency analysis, age-related theta oscillation response differences were observed within a relatively restricted time range (0 500 ms) over frontal-central regions. Older adults showed stronger theta spectral power during visual and audiovisual stimuli in the left frontal regions; however, young adults showed stronger theta spectral power during auditory and audiovisual stimuli in the central regions. These findings suggest that multisensory oscillatory theta responses differ according to age, which further proves that the left frontal regions play an important role in audiovisual integration. PMID- 27272689 TI - Postnatal high-fat diet leads to spatial deficit, obesity, and central and peripheral inflammation in prenatal dexamethasone adult offspring rats. AB - Synthetic glucocorticoids are frequently used in clinical practice for treating pregnant women at risk of preterm delivery, but their long-term effects on the infant brain are largely unknown. Pregnant Sprague-Dawley rats were administered vehicle or dexamethasone between gestational days 14 and 21. Male offspring were then weaned onto either a standard chow or a high-fat diet. The postnatal levels of insulin-like growth factor I (IGF-1), tumor necrosis factor-alpha (TNF-alpha), and asymmetric dimethylarginine (ADMA) in the plasma, liver, and brain were examined, as well as the possible effects of prenatal dexamethasone on cognition. We found that a postnatal high-fat diet led to spatial deficits detected by the Morris water maze in adult offspring administered dexamethasone prenatally. The spatial deficit was accompanied by decreased IGF-1 mRNA and increased ADMA levels in the dorsal hippocampus. In peripheral systems, a postnatal high-fat diet resulted in decreased plasma IGF-1, increased plasma corticosterone, increased concentrations of transaminases, TNF-alpha mRNA, and ADMA in the liver, and associated obesity in adult offspring administered prenatal dexamethasone. In conclusion, a postnatal high-fat diet led to spatial deficits, obesity, and altered levels of IGF-1, TNF-alpha, and ADMA in the plasma, liver, or brain. PMID- 27272691 TI - The Concept of the Arch Window in the Spiral Switch of the Great Arteries. AB - When the arterial switch operation includes the Lecompte maneuver, the arterial trunks are reconnected in parallel, rather than the spiral fashion observed in the normal heart. Thus, although the ventriculo-arterial connections are hemodynamically corrected, the anatomic arrangement cannot be considered normal. We hypothesized that, if feasible, it would be advantageous to restore a spiral configuration for the arterial trunks. In 58 patients, we reconstructed the arterial trunks such that, postoperatively, the pulmonary channel spirals round the aorta, passing to either the right or the left, and branches posteriorly. We compared the outcomes with those in 95 patients undergoing a standard non spiraling operation over the same period. Average follow-up was 8.2 +/- 4.5 years. The estimated 10-year survival was similar in the cohorts, at 94.7 % for those with spiraling trunks, as compared to 90.4 % for those with parallel outflow tracts. Reoperation-free survival at 10 years was not significantly different (87.6 vs. 90.5 %). Supravalvar pulmonary stenosis, aortic neo coarctation, or left bronchial stenosis, however, was encountered in one-eighth of those undergoing a standard operation. None of these complications occurred in those patients who, postoperatively, had spiraling outflow tracts (P = 0.002). Reconstruction of spiraling trunks after the arterial switch has, thus far, avoided the complications of supravalvar pulmonary stenosis, neo-aortic kinking, or bronchial stenosis. The spiraling arrangement prevents compression of the pulmonary vessels and bronchial tree by the aorta, since it provides a wide window in the new aortic arch. PMID- 27272692 TI - Predictors of Early Extubation After Pediatric Cardiac Surgery: A Single-Center Prospective Observational Study. AB - This prospective, observational, single-center study aimed to determine the perioperative predictors of early extubation (<24 h after cardiac surgery) in a cohort of children undergoing cardiac surgery. Children aged between 1 month and 18 years who were consecutively admitted to pediatric intensive care unit after cardiac surgery for congenital heart disease between January 2012 and June 2014. Ninety-nine patients were qualified for inclusion during the study period. The median duration of mechanical ventilation was 20 h (range 1-480), and 64 patients were extubated within 24 h. Four of them failed the initial attempt at extubation, and the success rate of early extubation was 60.6 %. Older patient age (p = .009), greater body weight (p = .009), absence of preoperative pulmonary hypertension (p = .044), lower RACHS-1 category (OR, 3.8; 95 % CI 1.35-10.7; p < .05), shorter cardiopulmonary bypass (p = .008) and cross-clamp (p = .022) times, lower PRISM III-24 (p < .05) and PELOD (p < .05) scores, lower inotropic score (p < .05) and vasoactive-inotropic score (p < .05), and lower number of organ failures (OR, 2.26; 95 % CI 1.30-3.92; p < .05) were associated with early extubation. Our study establishes that early extubation can be accomplished within the first 24 h after surgery in low- to medium-risk pediatric cardiac surgery patients, especially in older ones undergoing low-complexity procedures. A large prospective multiple institution trial is necessary to identify the predictors and benefits of early extubation and to facilitate defined guidelines for early extubation. PMID- 27272693 TI - Dexmedetomidine is Associated with an Increased Incidence of Bradycardia in Patients with Trisomy 21 After Surgery for Congenital Heart Disease. AB - This study aimed to evaluate adverse cardiac events using dexmedetomidine in infants with trisomy 21 and those without (controls) and examined potential risk factors in infants after cardiovascular surgery. We conducted a single-center retrospective cohort study. The medical records of 124 consecutive infants who had undergone cardiovascular surgery between April 1, 2013, and October 31, 2015, were enrolled. Clinical characteristics, usage of dexmedetomidine, and perioperative medications were analyzed. Adverse cardiac events were assessed with the Naranjo score and World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) criteria. In total, 124 consecutive infants (30 patients and 94 controls) met the inclusion criteria. Eight of 30 (26.7 %) patients with trisomy 21 and 12 of 94 (12.8 %) controls experienced adverse cardiac events (i.e., hypotension, transient hypertension, and bradycardia) during dexmedetomidine with median Naranjo score of 6, and causality categories of WHO-UMC criteria were "certain" or "probable." Of those, the incidence of bradycardia occurred at a higher rate in patients with trisomy 21 than in controls (P = 0.011). Multiple logistic regression analysis revealed that the presence of trisomy 21 was an independent risk factor for adverse cardiac events of dexmedetomidine after cardiovascular surgery (odds ratio 4.10, 95 % CI 1.17-11.19, P = 0.006). Dexmedetomidine is associated with an increased incidence of bradycardia in patients with trisomy 21 after surgery for congenital heart disease. Physicians using dexmedetomidine should know a great deal about the characteristics of patients with trisomy 21, and hemodynamic monitoring should be closely observed. PMID- 27272695 TI - Complexometric titrations: new reagents and concepts to overcome old limitations. AB - Chelators and end point indicators are the most important parts of complexometric titrations. The most widely used universal chelator ethylenediamine tetraacetic acid (EDTA) and its derivatives can strongly coordinate with different metal ions. Their limited selectivity often requires the use of masking agents, and the multiple pKa values of the chelators necessitate a careful adjustment of pH during the procedure. Real world requirements for pH independent, selective and sensitive chelators and indicators call for a new design of these reagents. New concepts and structures of chelators and indicators have indeed recently emerged. We present here recent developments on chelators and indicators for complexometric titrations. Many of these advances were made possible only recently by moving the titration from a homogeneous to a heterogeneous phase using a new class of chelators and indicators based on highly selective ionophores embedded in ion-selective nanosphere emulsions. In view of achieving titrations in situ by complete instrumental control, thin layer electrochemistry has recently been shown to be an attractive concept that replaces the traditional cumbersome titration protocol with a direct reagent free sensing tool. PMID- 27272694 TI - Is Endomyocardial Biopsy a Safe and Useful Procedure in Children with Suspected Cardiomyopathy? AB - Endomyocardial biopsy (EMB) is a common procedure used to aid in the diagnosis, prognosis and treatment of suspected pediatric cardiomyopathy. In suspected cardiomyopathy, no multicenter experience has previously reported on the safety and utility of EMBs. Retrospectively, adverse event (AE) and patient and procedural characteristics were obtained at seven institutions participating in the Congenital Cardiac Catheterization Outcomes Project for both a cardiomyopathy (n = 158) and a post-transplant surveillance (n = 2665) cohort. Descriptive information regarding biopsy indication, pathology and clinical management based on EMB findings were retrospectively obtained. High-severity AEs were more common in the cardiomyopathy cohort when compared to the post-transplant surveillance cohort. The cardiomyopathy cohort was younger, more hemodynamically vulnerable and required more cardiorespiratory support during the procedure. The eight high severity AEs in the cardiomyopathy group included one myocardial perforation, two ECMO cannulations and three deaths following the EMB. Factors associated with high-severity AEs included performing another catheter-based intervention during the EMB and longer fluoroscopy time. Notably, an increased number of biopsy attempts did not increase the risk of an AE. Suspected myocarditis was the most common indication. Diagnostic EMB pathology and thus alteration to clinical management based on pathology occurred more frequently in patients with suspected myocarditis. In conclusion, there is an increased incidence of high-severity AEs in patients undergoing EMB for suspected cardiomyopathy. EMB may be more clinically useful in the management of suspected myocarditis. The increased risk of high-severity AEs when additional interventions are performed highlights the hemodynamic vulnerability in patients with suspected cardiomyopathy. PMID- 27272696 TI - Effects of dietary supplementing tannic acid in the ration of beef cattle on rumen fermentation, methane emission, microbial flora and nutrient digestibility. AB - Four adult Simmental male cattle (376 +/- 9.0 kg initial BW), fitted with permanent rumen cannulas, were used in a 4 * 4 Latin square design to investigate the effects of dietary supplementing tannic acid (TA) on rumen fermentation, methane (CH4 ) production, rumen microbes, nutrient digestibility and plasma biochemical parameters. Four levels of TA, that is 0, 6.5, 13.0 or 26.0 g/kg dry matter (DM), were added to the basal ration (composed of corn silage and concentrate mixture) as experimental treatments respectively. Each experimental period consisted of a 12-day adaptation phase followed by a 3-day sampling phase. The results showed that supplementing TA at 26.0 g/kg DM decreased the relative abundance of protozoa, methanogens and Ruminococcus albus to the total ruminal bacterial 16S rDNA in beef cattle (p < 0.05). The results also showed that supplementing TA at 6.5, 13.0 or 26.0 g/kg DM decreased (p < 0.01) the CH4 production (l/kg DM intake) by 11.1%, 14.7% and 33.6% respectively. Supplementing TA at 13.0 or 26.0 g/kg DM decreased the ratio of acetate to propionate and ammonia nitrogen (NH3 -N) (p < 0.05) and tended to decrease the total volatile fatty acid (VFA) concentration of rumen fluid (p = 0.07). Supplementing TA at 26.0 g/kg DM decreased DM and organic matter (OM) digestibility (p < 0.05), supplementing TA at 6.5, 13.0 or 26.0 g/kg DM decreased (p < 0.01) crude protein (CP) digestibility by 5.0%, 8.6% and 15.7%, respectively, and supplementing TA at 6.5, 13.0 or 26.0 g/kg DM increased (p < 0.05) the plasma total antioxidant capability. It was concluded that supplementing TA in the ration of beef cattle decreased the CH4 production and digestibility of CP of beef cattle. Supplementing TA could be an effective option to mitigate CH4 emission form cattle, further research is necessary to study the effects of TA on the performance of cattle. PMID- 27272697 TI - Breath analysis for noninvasively differentiating Acinetobacter baumannii ventilator-associated pneumonia from its respiratory tract colonization of ventilated patients. AB - A number of multiresistant pathogens including Acinetobacter baumannii (A. baumannii) place a heavy burden on ventilator-associated pneumonia (VAP) patients in intensive care units (ICU). It is critically important to differentiate between bacterial infection and colonization to avoid prescribing unnecessary antibiotics. Quantitative culture of lower respiratory tract (LRT) specimens, however, requires invasive procedures. Nowadays, volatile organic compounds (VOCs) have been studied in vitro and in vivo to identify pathogen-derived biomarkers. Therefore, an exploratory pilot study was conceived for a proof of concept that the appearance and level of A. baumannii-derived metabolites might be correlated with the presence of the pathogen and its ecological niche (i.e. the infection and colonization states) in ICU ventilated patients. Twenty patients with A. baumannii VAP (infection group), 20 ventilated patients with LRT A. baumannii colonization (colonization group) and 20 ventilated patients with neurological disorders, but without pneumonia or A. baumannii colonization (control group) were enrolled in the in vivo pilot study. A clinical isolate of A. baumannii strains was used for the in vitro culture experiment. The adsorptive preconcentration (solid-phase microextraction fiber and Tenax((r)) TA) and analysis technique of gas chromatography-mass spectrometry were applied in the studies. Breath profiles could be visually differentiated between A. baumannii cultivation in vitro and culture medium, and among in vivo groups. In the in vitro experiment, nine compounds of interest (2,5-dimethyl-pyrazine, 1-undecene, isopentyl 3-methylbutanoate, decanal, 1,3-naphthalenediol, longifolene, tetradecane, iminodibenzyl and 3-methyl-indene) in the headspace were found to be possible A. baumannii derivations. While there were eight target VOCs (1 undecene, nonanal, decanal, 2,6,10-trimethyl-dodecane, 5-methyl-5-propyl-nonane, longifolene, tetradecane and 2-butyl-1-octanol) exhibiting characteristics of A. baumannii VAP derivations. The selected VOC profile in vivo could be adopted to efficiently differentiate the presence of LRT A. baumannii from its absence, and LRT A. baumannii infection from its colonization (AUC = 0.89 and 0.88, respectively). It is not feasible to simply transfer the metabolic biomarkers from the in vitro condition to in vivo. The direct detection of exhaled A. baumannii-derived VOCs may be adopted for an early alert of the LRT bacterial presence in ventilated ICU patients, and even in different parasitic states of A. baumannii (i.e. infection and colonization). However, further refinement and validation are required before its clinical use. PMID- 27272698 TI - Response to: Depolarization vs. repolarization: what is the mechanism of ventricular arrhythmogenesis underlying sodium channel haploinsufficiency in mouse hearts? PMID- 27272699 TI - Quantitative analysis of aliphatic amines in urban aerosols based on online derivatization and high performance liquid chromatography. AB - A method combining online derivatization with high performance liquid chromatography/fluorescence detection was developed for the determination of seven aliphatic amines (ethanolamine, methylamine, ethylamine, propylamine, butylamine, pentylamine and hexylamine) in urban aerosols. The collected amines were online derivatized with o-phthalaldehyde to form highly fluorescent sulfonatoisoindole derivatives. The derivatives were completely separated in 13 min through gradient elution and detected by fluorescence detection at an excitation wavelength of 334 nm and an emission wavelength of 443 nm. Under the optimized conditions, the relative standard derivations (RSDs) of all detected amines were 0.02-2.03% and 1.04-1.52% for the retention time and peak area, respectively. Excellent linearity was achieved for each analyte, ranging from 5 MUg L(-1) to 1000 MUg L(-1) (R(2) > 0.99). The detection limits for all analytes were below 1.1 MUg L(-1). The proposed method was used to analyze aliphatic amines in 35 samples of urban PM2.5 collected in Shanghai and was found to be suitable for the determination of particulate aliphatic amines at ng m(-3) levels in ambient air. Based on our measurements, ethanolamine and methylamine were the most abundant species on average in Shanghai during dry and wet seasons. The highest concentration was 15.3 ng m(-3) for ethanolamine and 13.2 ng m(-3) for methylamine. PMID- 27272700 TI - [Detection of Weissella spp. in milk samples of two dairy cows with clinical mastitis. A case report]. AB - This case report describes the isolation and differentiation of Weissella (W.) spp. from the milk of two cows (A and B) with clinical mastitis (milk changes, asymmetry of the udder and increased somatic cell counts). Quarter milk samples obtained from two dairy cows of different farms had been submitted to the diagnostic laboratory of the Clinic for Ruminants in Vienna for bacteriological examination. Alpha-hemolytic catalase-negative gram-positive cocci in pure culture on Columbia blood agar were isolated and could not be assigned to a Lancefield group. The isolates were biochemically characterized as Leuconostoc spp. (API(r) 20 Strep, bioMerieux). A control examination of cow B within 7 weeks confirmed these findings. 16S rDNA sequencing indicated W. paramesenteroides (cow A) and W. cibaria (cow B). The analysis by pulsed-field gel electrophoresis (PFGE) showed identical SmaI/ApaI profiles for both W. cibaria isolates (cow B), which differed from the W. paramesenteroides fingerprint of cow A (67% similarity). This study indicates a possible relationship between the detection of Weissella spp. and the occurrence of bovine intramammary infections. PMID- 27272701 TI - Integrated spatial health assessment of yellow perch (Perca flavescens) populations from the St. Lawrence River (QC, Canada), part B: cellular and transcriptomic effects. AB - Multi-biological level assessments have become great tools to evaluate the health of aquatic ecosystems. Using this approach, a complementary study was designed to evaluate the health of yellow perch (Perca flavescens) populations in the St. Lawrence River (Quebec, Canada). In the present study, stress responses were compared at the transcriptomic, cellular, and tissue levels in yellow perch collected at six sites along the river: Lake St. Francois, Lake St. Louis (north and south), Beauregard Island and Lake St. Pierre (north and south). These results complement the physiological and chemical parameters as well as pathogen infection investigated in a companion paper published in the present issue. Thiobarbituric acid reactive substance (TBARS) analyses indicated the presence of oxidative stress in fish collected in the southern part of Lake St. Louis and at the downstream sites of Lake St. Pierre. High lipid peroxidation levels were found in the muscle of yellow perch caught at Beauregard Island, located downstream of the Montreal's wastewater treatment plant, suggesting an impact of the municipal effluent on redox homeostasis. Transcriptomic results indicated the down-regulation of genes related to lipid, glucose, and retinoid in southern Lake St. Pierre as well as a decrease in retinoid storage. Overall, biochemical and molecular markers indicated that the health status of yellow perch followed a decreasing gradient from upstream to downstream of the St. Lawrence River. This gradient is representative of the cumulative negative impacts of human activities on water and habitat quality along the river. PMID- 27272702 TI - Biomass and lipid production from Nannochloropsis oculata growth in raceway ponds operated in sequential batch mode under greenhouse conditions. AB - The effect of sequential batch cultures of the marine microalgae Nannochloropsis oculata on lipid and biomass production was studied in 200-L raceway ponds for 167 days (nine harvesting cycles) during winter and spring seasons under greenhouse conditions. The highest biomass concentration and productivity were 1.2 g/L and 49.8 mg/L/day on days 73 (5th cycle) and 167 (9th cycle), respectively. The overall interval of lipid production was between 131 and 530 mg/L. Despite the daily and seasonal variations of light irradiance (0-1099 MUmol photon/m2 s), greenhouse temperature (2.1-50.7 degrees C), and culture temperature (12.5-31.4 degrees C), ANOVA analysis showed no statistical difference (p value > 0.01) on the fatty acid methyl ester (FAMES) composition over the nine harvesting cycles evaluated. The most abundant FAMES were palmitic (C16:0), stearic (C18:0) and palmitoleic (C16:1?9) acids with 37.1, 28.6, and 8.4 %, respectively. The sequential batch cultures of N. oculata in raceway ponds showed an increasing biomass production in each new cycle while keeping the quality of the fatty acid mixture under daily and seasonal variations of light irradiance and temperature. PMID- 27272703 TI - Long-term effects of antibiotics, norfloxacin, and sulfamethoxazole, in a partial life-cycle study with zebrafish (Danio rerio): effects on growth, development, and reproduction. AB - A partial life-cycle study with zebrafish (Danio rerio) was conducted to evaluate the long-term effects of antibiotics, norfloxacin (NOR) and sulfamethoxazole (SMX). A series of bio-endpoints correlated to the growth, development, and reproduction was assessed. The results showed that the body weight and the condition factor were depressed by SMX at 200 MUg/L during the growth period. Meanwhile, the activities of metabolic enzyme (ethoxyresorufin O-deethylase, EROD) and antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT) were stimulated in all cases. The consequences of parental exposure to antibiotics for the next generation were also examined. The egg production of parents were depressed by the 200 MUg/L NOR and SMX alone or in combination. Similarly, decreased hatching, survival, and enhanced development abnormality of the next generation also occurred after parental exposure to SMX at the highest concentration. The heartbeat however was not altered in all cases. Furthermore, there was no significant difference in the bio-endpoints between the combined and individual treatment in most cases, with the exception of lower EROD activity and egg production in the co-treatment. The results suggest that long-term exposure to NOR and SMX at environmentally relevant concentrations, individually and in a mixture, may not significantly pose a threat to the growth, development, and reproduction of zebrafish, and an adverse effect may be expected at high concentration. PMID- 27272704 TI - Diagnosing acute HIV infection at point of care: a retrospective analysis of the sensitivity and specificity of a fourth-generation point-of-care test for detection of HIV core protein p24. AB - OBJECTIVES: Detection of acute HIV infection is vital in preventing onward transmission. HIV point-of-care testing (POCT) has improved uptake of HIV testing but has been limited to third-generation assays, which only detect chronic HIV infection. Previous evaluation of the fourth-generation Alere Determine HIV-1/2 Ag/Ab Combo POCT showed only 50% sensitivity for HIV core protein p24 (p24 antigen) detection, which is suboptimal for diagnosis of acute HIV infection with limited advantage over third-generation POCT. We aimed to assess the sensitivity of the new Alere HIV Combo POCT to detect acute HIV infection. METHODS: Stored samples in samples already identified as p24-positive using standard-of-care fourth-generation assays were randomly selected alongside groups of antibody positive samples and HIV-negative samples. Each sample was tested using the new Alere POCT according to manufacturer's instructions. Sensitivity and specificity were then calculated. RESULTS: The Alere HIV Combo POCT test demonstrated 88% sensitivity 95% CI (78% to 98%) and 100% specificity 95% CI (99.7% to 100%) for detection of p24 antigen. CONCLUSIONS: This new POCT shows improved sensitivity for detection of p24 antigen and may be of value for clinical use in detecting acute HIV infection. Further evaluation of its use in a clinical setting is still required. PMID- 27272705 TI - How to diagnose and treat aerobic and desquamative inflammatory vaginitis. PMID- 27272706 TI - Estimates of the Public Health Impact of a Pediatric Vaccination Program Using an Intranasal Tetravalent Live-Attenuated Influenza Vaccine in Belgium. AB - OBJECTIVES: Our objectives were to estimate the public health outcomes of vaccinating Belgian children using an intranasal tetravalent live-attenuated influenza vaccine (QLAIV) combined with current coverage of high-risk/elderly individuals using the trivalent inactivated vaccine. METHODS: We used a deterministic, age-structured, dynamic model to simulate seasonal influenza transmission in the Belgian population under the current coverage or after extending vaccination with QLAIV to healthy children aged 2-17 years. Differential equations describe demographic changes, exposure to infectious individuals, infection recovery, and immunity dynamics. The basic reproduction number (R 0) was calibrated to the observed number of influenza doctor visits/year. Vaccine efficacy was 80 % (live-attenuated) and 59-68 % (inactivated). The 10-year incidence of symptomatic influenza was calculated with different coverage scenarios (add-on to current coverage). RESULTS: Model calibration yielded R 0 = 1.1. QLAIV coverage of 75 % of those aged 2-17 years averted 374,000 symptomatic cases/year (57 % of the current number), 244,000 of which were among adults (indirect effect). Vaccinating 75 % of those aged 2-11 years and 50 % of those aged 12-17 years averted 333,200 cases/year (213,000 adult cases/year). Vaccinating only healthy children aged 2-5 years generated direct protection but limited indirect protection, even with 90 % coverage (40,800 averted adult cases/year; -8.4 %). Targeting all children averted twice as many high-risk cases as targeting high-risk children only (8485 vs. 4965/year with 75 % coverage). Sensitivity analyses showed the robustness of results. CONCLUSIONS: The model highlights the direct and indirect protection benefits when vaccinating healthy children with QLAIV in Belgium. Policies targeting only high-risk individuals or the youngest provide limited herd protection, as school age children are important influenza vectors in the community. PMID- 27272707 TI - Can phenological models predict tree phenology accurately in the future? The unrevealed hurdle of endodormancy break. AB - The onset of the growing season of trees has been earlier by 2.3 days per decade during the last 40 years in temperate Europe because of global warming. The effect of temperature on plant phenology is, however, not linear because temperature has a dual effect on bud development. On one hand, low temperatures are necessary to break bud endodormancy, and, on the other hand, higher temperatures are necessary to promote bud cell growth afterward. Different process-based models have been developed in the last decades to predict the date of budbreak of woody species. They predict that global warming should delay or compromise endodormancy break at the species equatorward range limits leading to a delay or even impossibility to flower or set new leaves. These models are classically parameterized with flowering or budbreak dates only, with no information on the endodormancy break date because this information is very scarce. Here, we evaluated the efficiency of a set of phenological models to accurately predict the endodormancy break dates of three fruit trees. Our results show that models calibrated solely with budbreak dates usually do not accurately predict the endodormancy break date. Providing endodormancy break date for the model parameterization results in much more accurate prediction of this latter, with, however, a higher error than that on budbreak dates. Most importantly, we show that models not calibrated with endodormancy break dates can generate large discrepancies in forecasted budbreak dates when using climate scenarios as compared to models calibrated with endodormancy break dates. This discrepancy increases with mean annual temperature and is therefore the strongest after 2050 in the southernmost regions. Our results claim for the urgent need of massive measurements of endodormancy break dates in forest and fruit trees to yield more robust projections of phenological changes in a near future. PMID- 27272708 TI - Acne in adult women and the markers of peripheral 3 alpha-diol G activity. AB - BACKGROUND: Acne in adult women is a frequent hard-to-manage disease with many relapse cases. It mostly interferes with the quality of life of patients, bringing them major metabolic and social losses. As androgenic hormones play a very important role in the acne pathogenesis, the early diagnosis of hyperandrogenic states is very useful for the proper evaluation of each patient and for a better choice of therapeutic management. Defining a pattern for laboratory profile analysis is important for the control of relapses of acne breakouts in adult women, which lately has been the aim of many published studies. AIM: To establish the relation between 3 alpha-diol G levels and acne in female patients with normal androgenic status without menstrual dysfunctions. PATIENTS/METHODS: The evaluation of serum 3 alpha-androstanediol glucuronide levels through an enzymatic immunoassay method (Androstanediol Glucuronide ELISA Kit) for a direct quantitative measurement in 26 patients with grade II and III acne, ages ranging from 13 to 50. RESULTS: Among the analyzed patients, 83% had grade II acne, and among this total, 60% were aged 14 or over. According to age, 12 studied patients showed serum 3 alpha-diol G levels within normal range and 11 patients had increased levels. CONCLUSIONS: A total of 60% of adult women with acne present increased levels of androgens and among those with normal levels and without menstrual dysfunctions, 50% show an increase in 3 alpha-diol G. Therefore, a pharmacological approach with anti-androgenic drugs for acne therapy in most of these patients is advisable. PMID- 27272709 TI - Patient derived mutation W257G of PPP2R1A enhances cancer cell migration through SRC-JNK-c-Jun pathway. AB - Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A expression is elevated in high-grade primary tumor patients with papillary serous tumors of the ovary. To determine whether increased levels or mutation of PPP2R1A might contribute to cancer progression, the effects of overexpression or mutation of PPP2R1A on cell proliferation, migration, and PP2A phosphatase activity were investigated using ovarian and endometrial cancer cell lines. Among the mutations, PPP2R1A-W257G enhanced cell migration in vitro through activating SRC JNK-c-Jun pathway. Overexpression of wild type (WT) PPP2R1A increased its binding ability with B56 regulatory subunits, whereas PPP2R1A-mutations lost the ability to bind to most B56 subunits except B56delta. Total PP2A activity and PPP2R1A associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo. PMID- 27272710 TI - Transvenous Salvage of Migrated Large Volume Detachable Coil. PMID- 27272711 TI - Percutaneous Image-Guided Cryoablation of Challenging Mediastinal Lesions Using Large-Volume Hydrodissection: Technical Considerations and Outcomes. AB - OBJECTIVE: This study was designed to describe the technique of percutaneous image-guided cryoablation with large-volume hydrodissection for the treatment of challenging mediastinal lesions. METHODS: Between March 2014 and June 2015, three patients (mean age 62.7 years) with four neoplastic anterior mediastinal lesions underwent five cryoablation procedures using large-volume hydrodissection. Procedures were performed under general anaesthesia using CT guidance. Lesion characteristics, hydrodissection and cryoablation data, technical success, complications, and clinical outcomes were assessed using retrospective chart review. RESULTS: Lesions (mean size 2.7 cm; range 2-4.3 cm) were in contact with great vessels (n = 13), trachea (n = 3), and mediastinal nerves (n = 6). Hydrodissection was performed intercostally (n = 4), suprasternally (n = 2), transsternally (n = 1), or via the sternoclavicular joint (n = 1) using 1-3 spinal needles over 13.4 (range 7-26) minutes; 450 ml of dilute contrast was injected (range 300-600 ml) and increased mean lesion-collateral structure distance from 1.9 to 7.7 mm. Vulnerable mediastinal nerves were identified in four of five procedures. Technical success was 100 %, with one immediate complication (recurrent laryngeal nerve injury). Mean follow-up period was 15 months. One lesion demonstrated residual disease on restaging PET-CT and was retreated to achieve complete ablation. At last follow-up, two patients remained disease-free, and one patient developed distant disease after 1 year without local recurrence. CONCLUSIONS: Cryoablation using large-volume hydrodissection is a feasible technique, enabling safe and effective treatment of challenging mediastinal lesions. PMID- 27272712 TI - Endovascular Repair of a Type 1a Endoleak After Ch-EVAR with a b-EVAR. PMID- 27272713 TI - Percutaneous Transluminal Angioplasty for Complete Membranous Obstruction of Suprahepatic Inferior Vena Cava: Long-Term Results. AB - PURPOSE: To determine the long-term results of percutaneous transluminal angioplasty (PTA) for a complete membranous obstruction of the suprahepatic inferior vena cava. METHODS: Patients (n = 65) who were referred to the interventional unit for PTA for a complete membranous obstruction of the suprahepatic inferior vena cava between January 2006 and October 2014 were included in the study. Thirty-two patients (18 males, 14 females, mean age 35 +/- 10.7, range 20-42 years) were treated. The patients presented with symptoms of ascites (88 %), pleural effusion (53 %), varicose veins (94 %), hepatomegaly (97 %), abdominal pain (84 %), and splenomegaly (40 %). Transjugular liver access set and re-entry catheter were used to puncture and traverse the obstruction from the jugular side. PTA balloon dilations were performed. The mean follow-up period was 65.6 +/- 24.5 months. The objective was to evaluate technical success, complications, primary patency, and clinical improvement in the symptoms of the patients. RESULTS: The technical success rate was 94 %. In two patients, obstruction could not be traversed. These patients underwent cavoatrial graft bypass surgery. There were no procedure-related complications. Clinical improvements were achieved in all patients within 3 months. The primary patency rate at 4 years was 90 %. There was no primary assisted patency. There was no need for metallic stent deployment in the cohort. The secondary patency rate at 4 years was 100 %. CONCLUSIONS: Percutaneous transluminal angioplasty for a complete membranous obstruction of the suprahepatic inferior vena cava is safe and effective, and the long-term results are excellent. PMID- 27272714 TI - Primary vitrectomy for rhegmatogenous retinal detachment in pseudophakic eyes: 20 gauge versus 25-gauge vitrectomy. AB - PURPOSE: To report anatomical and functional outcome of 20-gauge versus 25-gauge primary pars plana vitrectomy for management of complex rhegmatogenous retinal detachment in pseudophakic eyes. METHODS: Prospective single-centre randomized comparative pilot trial. Fifty patients with retinal detachment (RD) not complicated by proliferative vitreoretinopathy grade B or C, who cannot be treated with a single meridional sponge, were randomized (1:1) from November 2006 to January 2010 to either 20-gauge or 25-gauge vitrectomy as first surgical intervention and followed up over a 12-month period, evaluating change in best corrected visual acuity, anatomical success and intraocular pressure dysregulation. RESULTS: Mean visual acuity improved by 0.88 (SD 0.67) from 1.22 logMAR (SD 0.63) to 0.34 logMAR (SD 0.31) in the 20-gauge group and by 0.53 (SD 0.91) from 0.86 logMAR (SD 0.73) to 0.34 logMAR (SD 0.46) in the 25-gauge group. Final anatomical success rate was 100% and primary success rate was 69% at 6 months of follow-up. In the 20-gauge group, the retina was attached after one single procedure in 18 eyes (72%) and in 21 eyes (84%) of the 25-gauge group. Two patients in the 25-gauge group had hypotony at the first postoperative day which normalized within 6 weeks. CONCLUSION: In our series, transconjunctival sutureless 25-gauge and 20-gauge vitrectomy showed comparable results in pseudophakic RD not suitable for single sponge surgery with respect to visual outcome and retinal reattachment. Postoperative hypotony does not seem to be a significant problem of transconjunctival sutureless vitrectomy. PMID- 27272715 TI - Association of Serum Selenium, Zinc and Magnesium Levels with Glycaemic Indices and Insulin Resistance in Pre-diabetes: a Cross-Sectional Study from South India. AB - A growing understanding of antioxidant mechanisms and insulin-like actions of trace elements selenium and zinc has rekindled researchers' interest towards their role in diabetes mellitus, nutritional management of which concentrates predominantly on macronutrient intake. However, selenium studies limiting largely to diabetes have yielded inconsistent results with sparse knowledge in the pre diabetes population. This hospital-based cross-sectional study screened 300 people who came to the institutional hospital laboratory with fasting plasma glucose and glycosylated haemoglobin requisition over a period of 6 months. Thirty-five pre-diabetes subjects aged 25-45 years and 35 age-matched healthy controls were selected as per inclusion criteria and clinical history. Serum selenium was estimated by inductively coupled plasma-mass spectrometry, zinc and magnesium by colorimetric end-point methods and insulin by enzyme-linked immunosorbent assay, and insulin resistance was calculated using a homeostasis model assessment (HOMA) 2 calculator. Data analysis was done using SPSS ver. 16 employing an independent sample t test for intergroup comparison of means and Pearson's correlation for correlation analysis. Serum mineral levels in the pre diabetes group (selenium 63.01 +/- 17.6 MUg/L, zinc 55.78 +/- 13.49 MUg/dL, magnesium 1.37 +/- 0.38 mg/dL) were significantly reduced (p < 0.05) in comparison to the healthy controls (selenium 90.98 +/- 15.81 MUg/L, zinc 94.53 +/ 15.41 MUg/dL, magnesium 2.12 +/- 0.22 mg/dL). A significant negative correlation was seen with glycaemic indices and insulin resistance. This study conducted in pre-diabetes subjects highlights a considerable deficiency of serum selenium, zinc and magnesium observed at a much earlier pre-clinical phase. This coupled with the evidence of a strong inverse association with glycaemic indices and insulin resistance postulates the role of mineral alterations in the pathophysiology of hyperglycaemia and insulin resistance. PMID- 27272716 TI - The Association Between Urinary Cadmium Levels and Dietary Habits with Risk of Gastrointestinal Cancer in Tabriz, Northwest of Iran. AB - Cadmium (Cd) is a widespread toxic heavy metal and has long biological half-life. It has potential carcinogenic effects on multiple organ systems of human. However, no studies have evaluated the adverse effects of cadmium on incidence of cancer in gastrointestinal tract. The aim of this study was to investigate the association between urine cadmium (U-Cd) levels and risk of gastrointestinal cancer. This descriptive study was accomplished on 111 GI cancer patients as cases and 111 healthy people as control subjects from January to October in Tabriz, northwest Iran, during 2013. Cadmium in urine samples was measured by graphite furnace atomic absorption spectrophotometer (GFAAS). GI cancer patients had higher urine cadmium levels in comparison to healthy individuals (p < 0.05). The multivariate regression model manifested a significant association between the U-Cd concentrations and the risk of GI cancer (odds ratio (OR) = 1.70, 95 % CI = 1.35-2.20). Cases were 70 % more than controls at risk of cancer incidence. Our data indicates an association between U-Cd levels and GI cancer risk. PMID- 27272717 TI - Coexistence of Copper in the Iron-Rich Particles of Aceruloplasminemia Brain. AB - The interaction between iron and copper has been discussed in association with human health and diseases for many years. Ceruloplasmin, a multi-copper oxidase, is mainly involved in iron metabolism and its genetic defect, aceruloplasminemia (ACP), shows neurological disorders and diabetes associated with excessive iron accumulation, but little is known about the state of copper in the brain. Here, we investigated localization of these metals in the brains of three patients with ACP using electron microscopes equipped with an energy-dispersive x-ray analyzer. Histochemically, iron deposition was observed mainly in the basal ganglia and dentate nucleus, and to lesser degree in the cerebral cortex of the patients, whereas copper grains were not detected. X-ray microanalysis identified two types of iron-rich particles in their brains: dense bodies, namely hemosiderins, and their aggregated inclusions. A small number of hemosiderins and most inclusions contained a significant amount of copper which was enough for distinct Cu x-ray images. These copper-containing particles were observed more frequently in the putamen and dentate nucleus than the cerebral cortex. Coexistence of iron and copper was supported by good correlations in the molecular ratios between these two metals in iron-rich particles with Cu x-ray image. Iron-dependent copper accumulation in iron-rich particles may suggest that copper recycling is enhanced to meet the increased requirement of cuproproteins in iron overload brain. In conclusion, the iron-rich particles with Cu x-ray image were found in the ACP brain. PMID- 27272718 TI - Selenium Levels in the Whole Blood of Children and Teenagers from Two Riparian Communities at the Madeira River Basin in the Western Brazilian Amazon. AB - Selenium (Se) is an essential micronutrient that exerts multiple functions in the organism, and both its deficiency and excess can cause health impairments. Thus, it is important to monitor its levels in the population, especially in vulnerable groups, such as children from the Brazilian Amazon region, where there is a lack of information in this regard. The aim of this research was to study Se levels in the whole blood of children and teenagers (5-16 years old) from two riparian communities at the Madeira River (Cunia RESEX and Belmont). Se level variations related to the communities' location, seasonality, diet, and body mass index (BMI) were assessed. Blood samples were collected in both communities for Se determinations, using ICP-MS and hemogram analyses, during May and September of 2011. Food frequency questionnaires were applied to assess consumption rates of specific food items. Non-parametric tests and linear multiple regressions were applied in the data analyses. Median Se levels were significantly higher during May (Cunia RESEX 149 MUg L-1; Belmont 85 MUg L-1) compared to September (Cunia RESEX 79 MUg L-1; Belmont 53 MUg L-1). No significant differences were found between the communities regarding BMI measurements and anemia prevalence. However, Se blood levels were significantly higher at the Cunia RESEX compared to Belmont. In addition, the former showed higher fish and Brazil nut intakes, which may be the main Se sources for this community. These results contribute to a better understanding of Se reference levels for children and teenagers of Western Amazon riparian communities. PMID- 27272719 TI - Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms. AB - We performed a whole-transcriptome analysis of miconazole-treated Candida albicans biofilms, using RNA-sequencing. Our aim was to identify molecular pathways employed by biofilm cells of this pathogen to resist action of the commonly used antifungal miconazole. As expected, genes involved in sterol biosynthesis and genes encoding drug efflux pumps were highly induced in biofilm cells upon miconazole treatment. Other processes were affected as well, including the electron transport chain (ETC), of which eight components were transcriptionally downregulated. Within a diverse set of 17 inhibitors/inducers of the transcriptionally affected pathways, the ETC inhibitors acted most synergistically with miconazole against C. albicans biofilm cells. Synergy was not observed for planktonically growing C. albicans cultures or when biofilms were treated in oxygen-deprived conditions, pointing to a biofilm-specific oxygen dependent tolerance mechanism. In line, a correlation between miconazole's fungicidal action against C. albicans biofilm cells and the levels of superoxide radicals was observed, and confirmed both genetically and pharmacologically using a triple superoxide dismutase mutant and a superoxide dismutase inhibitor N-N' diethyldithiocarbamate, respectively. Consequently, ETC inhibitors that result in mitochondrial dysfunction and affect production of reactive oxygen species can increase miconazole's fungicidal activity against C. albicans biofilm cells. PMID- 27272720 TI - Adhesion Molecules Associated with Female Genital Tract Infection. AB - Efforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. alpha4beta7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as alpha4beta1 and alpha4beta7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes. PMID- 27272722 TI - Pharmacokinetics and total removal of fosfomycin in two patients undergoing intermittent haemodialysis and extended dialysis: prescription needs to avoid under-dosing. PMID- 27272721 TI - Efficacy of OZ439 (artefenomel) against early Plasmodium falciparum blood-stage malaria infection in healthy volunteers. AB - OBJECTIVES: OZ439, or artefenomel, is an investigational synthetic ozonide antimalarial with similar potency, but a significantly improved pharmacokinetic profile, compared with artemisinins. We wished to measure key pharmacokinetic and pharmacodynamic parameters and the pharmacokinetic/pharmacodynamic relationship of artefenomel in humans to guide the drug's further development as combination therapy in patients. PATIENTS AND METHODS: We tested artefenomel in the human induced blood-stage malaria (IBSM) model. Plasmodium infection was monitored by quantitative PCR (qPCR) and upon reaching 1000 parasites/mL single doses of 100, 200 and 500 mg of artefenomel were administered orally with evaluation of drug exposure and parasitaemia until rescue treatment after 16 days or earlier, if required. RESULTS: A single 100 mg dose had only a transient effect, while the 200 mg dose resulted in a significant reduction in parasitaemia before early recrudescence. At the highest (500 mg) dose, initial clearance of parasites below the limit of detection of qPCR was observed, with a 48 h parasite reduction ratio (PRR48) >10 000 and a parasite clearance half-life of 3.6 h (95% CI 3.4-3.8 h). However, at this dose, recrudescence was seen in four of eight subjects 6-10 days after treatment. Pharmacokinetic/pharmacodynamic modelling predicted an MIC of 4.1 ng/mL. CONCLUSIONS: These results confirm the antimalarial potential of artefenomel for use in a single-exposure combination therapy. The observations from this study support and will assist further clinical development of artefenomel. PMID- 27272724 TI - Combination of Candida biomarkers in patients receiving empirical antifungal therapy in a Spanish tertiary hospital: a potential role in reducing the duration of treatment. PMID- 27272723 TI - Pharmacodynamics of carbapenems for the treatment of Pseudomonas aeruginosa ventilator-associated pneumonia: associations with clinical outcome and recurrence. AB - OBJECTIVES: This study was designed to evaluate the pharmacodynamics of doripenem, imipenem and meropenem as a predictor of clinical success, mortality, 28 day recurrence and development of resistance in patients treated for Pseudomonas aeruginosa ventilator-associated pneumonia (VAP). PATIENTS AND METHODS: Previously published demographic and outcome data derived from patients treated for P. aeruginosa VAP with doripenem, imipenem or meropenem were utilized. Patient-specific data were used in conjunction with published population pharmacokinetic models to construct concentration-time profiles for each patient. Etest MICs were used to determine pharmacodynamic profiles. Classification and regression tree (CART) analysis was utilized to partition pharmacodynamics based on outcomes with P values of 0.05. RESULTS: Eighty-six patients were included in the analysis. Initial carbapenem MICs ranged from 0.03 to 32 mg/L. VAP recurred in 28 patients; of these, 17 patients were initially infected with susceptible organisms, and 14 of them developed resistance. CART fT>MIC partitions identified for clinical success and survival were 19.2% (P = 0.016) and 47.9% (P < 0.001), respectively. No statistically significant partitions for fT>MIC were identified for recurrence or resistance development. CONCLUSIONS: We identified fT>MIC cut-offs for positive clinical outcomes in patients with P. aeruginosa VAP that were similar to those observed in animal models of infection for stasis (~20%) and 1 log decreases in cfu (~40%). Although in vitro studies have suggested a link between drug exposure and development of resistance, we were unable to identify such a relationship clinically. PMID- 27272725 TI - Adaptive responses to cefotaxime treatment in ESBL-producing Escherichia coli and the possible use of significantly regulated pathways as novel secondary targets. AB - OBJECTIVES: The aim of the study was to determine how ESBL-producing Escherichia coli change the expression of metabolic and biosynthesis genes when adapting to inhibitory concentrations of cefotaxime. Secondly, it was investigated whether significantly regulated pathways constitute putative secondary targets that can be used to combat the resistant bacteria. METHODS: Strains of E. coli MG1655 encoding blaCTX-M-1 from an IncI1 plasmid and from the chromosome were challenged with cefotaxime corresponding to inhibitory concentrations, and transcriptional patterns were compared with growth without or with very low concentrations of cefotaxime by RNA sequencing. Significantly regulated pathways were inhibited with suitable inhibitors, or genes encoding the enzymes of the regulated pathways were knocked out. The ability of the bacteria to grow in the presence of cefotaxime was determined. Chequerboard assays were utilized to confirm synergies between treatments. RESULTS: Genes belonging to 16 different functional gene classes were significantly regulated. Protein and peptidoglycan syntheses were up regulated and low concentrations of chloramphenicol or d-cycloserine, targeting these systems, strongly reduced the MIC of cefotaxime (>32-fold). Inhibition and/or mutations in other genes that were significantly regulated, belonging to energy synthesis, purine synthesis, proline uptake or potassium uptake, also rendered the resistant bacteria more susceptible to cefotaxime. CONCLUSIONS: The results show that ESBL-producing E. coli adapt to treatment with cefotaxime by changing their gene expression patterns and furthermore that targeting regulated adaptive pathways may be a suitable way to identify targets for drugs that will specifically inhibit the resistant bacteria. PMID- 27272726 TI - A novel small-molecule compound disrupts influenza A virus PB2 cap-binding and inhibits viral replication. AB - OBJECTIVES: The conserved residues 318-483 in the PB2 subunit of influenza A polymerase is an independently folded cap-binding domain (PB2cap) that exhibits a distinct binding mode from other host cap-binding proteins, which suggests that PB2cap might be an ideal drug target. This study aimed to identify a new class of anti-influenza inhibitors that specifically disrupts the interaction between PB2cap and host cap structures. METHODS: An innovative fluorescence polarization assay was established for primary screening, followed by cap-binding inhibitory activity, antiviral efficacy and cytotoxicity evaluations of the selected compounds. The best compound was characterized by multi-cycle virus growth assay, cross-protection test, synergism evaluation, mini-replicon assay, binding affinity analysis, docking simulation and mouse study. RESULTS: Several PB2 cap binding inhibitors were discovered. The compound 7-(4-hydroxy-2-oxo-2H-chromen-3 yl)-6H,7H,8H-chromeno[3',4':5,6]pyrano[3,2-c]chromene-6,8-dione, designated PB2 39, was identified as a potent inhibitor of replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 in vitro and H1N1, H5N1 and H7N9 in vivo. Combinational treatment with the influenza virus release inhibitor zanamivir and PB2-39 exerted a synergistic anti-influenza effect. Mechanistic experiments supported that PB2-39 suppressed viral polymerase activity. Docking and binding affinity analyses demonstrated that PB2-39 interacted with the PB2 cap-binding pocket, suggesting its role as a cap-binding competitor. CONCLUSIONS: Our study provides new insights for the strategic development of novel cap-binding inhibitors of influenza A viruses. PMID- 27272730 TI - Is there really a shortage of primary care PAs? PMID- 27272728 TI - Antimicrobial Activity of Serbian Propolis Evaluated by Means of MIC, HPTLC, Bioautography and Chemometrics. AB - New information has come to light about the biological activity of propolis and the quality of natural products which requires a rapid and reliable assessment method such as High Performance Thin-Layer Chromatography (HPTLC) fingerprinting. This study investigates chromatographic and chemometric approaches for determining the antimicrobial activity of propolis of Serbian origin against various bacterial species. A linear multivariate calibration technique, using Partial Least Squares, was used to extract the relevant information from the chromatographic fingerprints, i.e. to indicate peaks which represent phenolic compounds that are potentially responsible for the antimicrobial capacity of the samples. In addition, direct bioautography was performed to localize the antibacterial activity on chromatograms. The biological activity of the propolis samples against various bacterial species was determined by a minimum inhibitory concentration assay, confirming their affiliation with the European poplar type of propolis and revealing the existence of two types (blue and orange) according to botanical origin. The strongest antibacterial activity was exhibited by sample 26 against Staphylococcus aureus, with a MIC value of 0.5 mg/mL, and Listeria monocytogenes, with a MIC as low as 0.1 mg/mL, which was also the lowest effective concentration observed in our study. Generally, the orange type of propolis shows higher antimicrobial activity compared to the blue type. PLS modelling was performed on the HPTLC data set and the resulting models might qualitatively indicate compounds that play an important role in the activity exhibited by the propolis samples. The most relevant peaks influencing the antimicrobial activity of propolis against all bacterial strains were phenolic compounds at RF values of 0.37, 0.40, 0.45, 0.51, 0.60 and 0.70. The knowledge gained through this study could be important for attributing the antimicrobial activity of propolis to specific chemical compounds, as well as the verification of HPTLC fingerprinting as a reliable method for the identification of compounds that are potentially responsible for antimicrobial activity. This is the first report on the activity of Serbian propolis as determined by several combined methods, including the modelling of antimicrobial activity by HPTLC fingerprinting. PMID- 27272729 TI - Glycogen dynamics of crucian carp (Carassius carassius) in prolonged anoxia. AB - Mobilization of glycogen stores was examined in the anoxic crucian carp (Carassius carassius Linnaeus). Winter-acclimatized fish were exposed to anoxia for 1, 3, or 6 weeks at 2 degrees C, and changes in the size of glycogen deposits were followed. After 1 week of anoxia, a major part of the glycogen stores was mobilized in liver (79.5 %) and heart (75.6 %), and large decreases occurred in gill (46.7 %) and muscle (45.1 %). Brain was an exception in that its glycogen content remained unchanged. The amount of glycogen degraded during the first anoxic week was sufficient for the anaerobic ethanol production for more than 6 weeks of anoxia. After 3 and 6 weeks of anoxia, there was little further degradation of glycogen in other tissues except the brain where the stores were reduced by 30.1 and 49.9 % after 3 and 6 weeks of anoxia, respectively. One week of normoxic recovery following the 6-week anoxia was associated with a complete replenishment of the brain glycogen and partial recovery of liver, heart, and gill glycogen stores. Notably, the resynthesis of glycogen occurred at the expense of the existing energy reserves of the body in fasting fish. These findings indicate that in crucian carp, glycogen stores are quickly mobilized after the onset of anoxia, with the exception of the brain whose glycogen stores may be saved for putative emergency situations. PMID- 27272731 TI - Chronic kidney disease-mineral and bone disorder: Guidelines for diagnosis, treatment, and management. AB - Chronic kidney disease affects 23 million Americans and is associated with many complications, one of the most complex of which is mineral and bone disorder. Pathophysiologic mechanisms begin to occur early in CKD but when the glomerular filtration rate declines to <50% of normal, biochemical and bone matrix abnormalities, which vary and are multifactorial, begin to be clinically apparent. Mainstays of treatment remain management of hyperphosphatemia and prevention or treatment of secondary hyperparathyroidism. PMID- 27272732 TI - Correcting four decades of the wrong dietary advice. PMID- 27272727 TI - Triglyceride/HDL ratio and its impact on the risk of diabetes mellitus development during ART. AB - OBJECTIVES: Our primary aim was to study diabetes mellitus (DM) arising during combination ART (cART) and to attempt to identify associations between these cases and triglycerides (TRG) and the TRG to HDL-cholesterol (TRG/HDL) ratio. Our secondary aim was to analyse the association between DM development and hepatic fibrosis. METHODS: This was a retrospective cohort study. Patients from the Icona Foundation study initiating first-line cART between 1997 and 2013 were selected and observed until new-onset DM or most recent clinical follow-up. The predictive value of TRG and TRG/HDL ratio levels on DM was evaluated using multivariable Poisson regression models. RESULTS: Three-thousand, five-hundred and forty-six patients (males, 73.7%; median age, 38 years; median BMI, 23.1 kg/m(2); and hepatitis C virus antibody positive, 22.1%) were included. Of these, 80 developed DM over 13 911 person-years of follow-up (PYFU), corresponding to 5.7 cases per 1000 PYFU (95% CI = 4.6-7.1). At multivariable analysis, latest TRG/HDL ratio, when high, was associated with significant increases in DM risk [relative risk (RR) = 1.63; 95% CI = 1.32-2.01 per 10 points higher], while current TRG, in contrast, was associated with new-onset DM only at crude analysis. Advanced liver fibrosis (defined as fibrosis-4 index >3.25) was also shown to be an independent risk factor for DM (RR = 2.91; 95% CI = 1.10-7.72). CONCLUSIONS: High TRG/HDL ratio predicted risk of new-onset DM, independently of other traditional risk factors. Furthermore, our findings suggest that advanced hepatic fibrosis, estimated using the fibrosis-4 score, could provide an additional predictor for DM. PMID- 27272734 TI - Dos and don'ts for hospital cleaning. AB - PURPOSE OF REVIEW: More evidence is emerging on the role of cleaning and decontamination for reducing hospital-acquired infection. Timely and adequate removal of environmental pathogens leads to measurable clinical benefits for patients. This article considers studies published from 2013 examining hospital decontamination technologies and evidence for cost-effectiveness. RECENT FINDINGS: Novel biocides and cleaning products, antimicrobial coatings, monitoring practices and automated equipment are widely accessible. They do not necessarily remove all environmental pathogens, however, and most have yet to be comprehensively assessed against patient outcome. Some studies are confounded by concurrent infection control and/or antimicrobial stewardship initiatives. Few contain data on costs. SUMMARY: As automated dirt removal is assumed to be superior to human effort, there is a danger that traditional cleaning methods are devalued or ignored. Fear of infection encourages use of powerful disinfectants for eliminating real or imagined pathogens in hospitals without appreciating toxicity or cost benefit. Furthermore, efficacy of these agents is compromised without prior removal of organic soil. Microbiocidal activity should be compared and contrasted against physical removal of soil in standardized and controlled studies to understand how best to manage contaminated healthcare environments. PMID- 27272733 TI - RAB-10 Promotes EHBP-1 Bridging of Filamentous Actin and Tubular Recycling Endosomes. AB - EHBP-1 (Ehbp1) is a conserved regulator of endocytic recycling, acting as an effector of small GTPases including RAB-10 (Rab10). Here we present evidence that EHBP-1 associates with tubular endosomal phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] enriched membranes through an N-terminal C2-like (NT-C2) domain, and define residues within the NT-C2 domain that mediate membrane interaction. Furthermore, our results indicate that the EHBP-1 central calponin homology (CH) domain binds to actin microfilaments in a reaction that is stimulated by RAB 10(GTP). Loss of any aspect of this RAB-10/EHBP-1 system in the C. elegans intestinal epithelium leads to retention of basolateral recycling cargo in endosomes that have lost their normal tubular endosomal network (TEN) organization. We propose a mechanism whereby RAB-10 promotes the ability of endosome-bound EHBP-1 to also bind to the actin cytoskeleton, thereby promoting endosomal tubulation. PMID- 27272735 TI - Both muscle mass and muscle strength are inversely associated with depressive symptoms in an elderly Chinese population. AB - OBJECTIVE: Few population studies have examined the association between skeletal muscle and depressive symptoms. The aim of this study was to examine whether low muscle mass and muscle strength were associated with the depressive symptoms in elderly Chinese. METHODS: A cross-sectional study was conducted with 1046 elderly in Tianjin, China. Depressive symptoms were examined using the 30-item Geriatric Depression Scale. A Geriatric Depression Scale score of >=11 was used to indicate depressive symptoms. Skeletal muscle mass was indicated using a skeletal muscle mass index (SMI) that was measured by bioimpedance analysis and muscle strength was measured by dynamometer. RESULTS: In a multiple logistic regression analysis, subjects in the lowest quartile of SMI or muscle strength had a significantly higher risk for depressive symptoms compared with those in the fourth quartile. The odds ratios and 95% confidence interval for depressive symptoms risk in the lowest quartile of SMI compared with the highest after adjusting for potential confounding factors were 10.1 (2.25, 58.3) in men and 3.17 (1.07, 9.95) in women. The odds ratios (95% confidence interval) for depressive symptoms risk in the lowest quartile of muscle strength compared with the highest after adjusting for potential confounding factors were 2.55 (1.02, 6.67) in men and 4.18 (1.83, 10.2) in women. CONCLUSIONS: Both muscle mass and muscle strength are inversely associated with depressive symptoms in elderly Chinese. These findings may provide novel insights linking skeletal muscle and depressive symptoms. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27272736 TI - Variation of outdoor illumination as a function of solar elevation and light pollution. AB - The illumination of the environment undergoes both intensity and spectral changes during the 24 h cycle of a day. Daylight spectral power distributions are well described by low-dimensional models such as the CIE (Commission Internationale de l'Eclairage) daylight model, but the performance of this model in non-daylight regimes is not characterised. We measured downwelling spectral irradiance across multiple days in two locations in North America: One rural location (Cherry Springs State Park, PA) with minimal anthropogenic light sources, and one city location (Philadelphia, PA). We characterise the spectral, intensity and colour changes and extend the existing CIE model for daylight to capture twilight components and the spectrum of the night sky. PMID- 27272737 TI - Imaging the Bonds of Dehalogenated Benzene Radicals on Cu(111) and Au(111). AB - Dissociative adsorption of doubly substituted benzene molecules leads to formation of benzyne radicals. In this study, co-adsorbed hydrogen molecules are used in scanning tunneling hydrogen microscopy to enhance the contrast of the meta- and the para-isomers of these radicals on Cu(111) and Au(111). Up to three hydrogen molecules are attached to one radical. One hydrogen molecule reveals the orientation of the carbon ring and its adsorption site, allowing discrimination between the two radicals. Two hydrogen molecules reflect the bond picture of the carbon skeleton and reveals that adsorption on Cu(111) distorts the meta- isomer differently from its gas-phase distortion. Three hydrogen molecules allow us to determine the bond picture of a minor species. PMID- 27272738 TI - Long-term mindfulness training is associated with reliable differences in resting respiration rate. AB - Respiration rate is known to correlate with aspects of psychological well-being, and attention to respiration is a central component of mindfulness meditation training. Both traditional contemplative systems and recent empirical evidence support an association between formal mindfulness practice and decreased respiration rate. However, the question of whether long-term mindfulness training is associated with stable, generalized changes in respiration has yet to be directly investigated. We analyzed respiration patterns across multiple time points, separated by two months or more, in a group of long-term mindfulness meditation practitioners (LTMs, n = 31) and a matched group of non-meditators (Controls, n = 38). On average, LTMs showed slower baseline respiration rate (RR) than Controls. Among LTMs, greater practice experience was associated with slower RR, independently of age and gender. Furthermore, this association was specific to intensive retreat practice, and was not seen for routine daily practice. Full days of meditation practice did not produce detectable changes in baseline RR, suggesting distal rather than immediate effects. All effects were independent of physiological characteristics including height, weight, body-mass index and waist hip ratio. We discuss implications for continued study of the long-term effects of mindfulness training on health and well-being. PMID- 27272739 TI - Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population. AB - Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unknown etiology to both forensic pathologists and physicians. The electrocardiogram (ECG) characteristics and clinical phenotype of SUNDS survivors strongly suggest that SUNDS shares some similarities with Brugada syndrome (BrS). Recently, the variants of sodium channel Nav 1.8 coding gene SCN10A were identified to be associated with BrS. Here, we investigated the association of SCN10A gene variants with 105 sporadic SUNDS victims and 22 BrS cases in the Chinese Han population. A total of 6 rare mutations and 16 polymorphisms were detected in SUNDS victims. Of the six rare mutations, two were putative pathogenic mutations (F386C and R1263*), one was a likely pathogenic mutation (R14H), and the other three were predicted as benign (R817Q, T1181M, and P1683S). As for the 16 polymorphisms, 1 was a novel polymorphism (c.4144-84G>A) located in intron 24, and the rest were reported previously including one polymorphism (c.2884A>G [I962V]) which showed a statistically significant difference in allele frequency (p = 0.044) between SUNDS and the control group. There were also 5 rare mutations and 15 polymorphisms detected in BrS cases. This is the first report of common and rare variants of SCN10A gene in SUNDS and BrS in the Chinese Han population, which provides the genetic epidemiological evidence that SCN10A may be a novel susceptibility gene for SUNDS and account for approximately 3 % of SUNDS in China. PMID- 27272741 TI - The impact of a community mental health initiative on outcomes for offenders with a serious mental disorder. AB - BACKGROUND: The Community Mental Health Initiative (CMHI) is mandated to assist offenders with serious mental disorders in their transition from institutions to the community, but this incorporates different styles of service. An important unanswered question is whether these are equivalent. AIMS/HYPOTHESES: Our aim was to compare outcomes for different intervention styles within the CMHI, a programme for serious offenders in prison who also have at least one major mental disorder. Our specific research questions were as follows: do outcomes differ according to whether offenders with mental health difficulties receive (1) clinical discharge planning only; (2) community mental health services only; (3) the combined services or (4) none, although meeting criteria for any CMHI service? METHODS: Survival analyses, controlling for variables with a significant effect on recidivism or return to prison, were used to test for differences in recidivism or return to prison rates between the intervention and no-intervention groups during a fixed follow-up period. RESULTS: Men receiving only community mental health services had a significantly lower risk of returning to custody and of recidivism than men receiving discharge planning alone or no community mental health service at all, even after controlling for potential confounders including age, number of previous imprisonments and number of previous community failures. The advantages were apparent within 3-6 months and sustained for up to 4 years. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Provision of specialised community mental health services for higher-risk male offenders with a mental disorder may reduce recidivism in the short and longer term - within 3 months and up to 4 years respectively. Statistical modelling also pointed to the need to include treatment for substance abuse and assistance in identifying stable accommodation and brokerage of community services among the interventions and services. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27272740 TI - Brain edema: a valid endpoint for measuring hepatic encephalopathy? AB - Hepatic encephalopathy (HE) is a major complication of liver failure/disease which frequently develops during the progression of end-stage liver disease. This metabolic neuropsychiatric syndrome involves a spectrum of symptoms, including cognition impairment, attention deficits and motor dysfunction which eventually can progress to coma and death. Pathologically, HE is characterized by swelling of the astrocytes which consequently leads to brain edema, a common feature found in patients with acute liver failure (ALF) as well as in cirrhotic patients suffering from HE. The pathogenic factors involved in the onset of astrocyte swelling and brain edema in HE are unresolved. However, the role of astrocyte swelling/brain edema in the development of HE remains ambiguous and therefore measuring brain edema as an endpoint to evaluate HE is questioned. The following review will determine the effect of astrocyte swelling and brain edema on neurological function, discuss the various possible techniques to measure brain edema and lastly to propose a number of neurobehavioral tests to evaluate HE. PMID- 27272743 TI - The value of sentinel lymph node biopsy in Merkel cell carcinoma. PMID- 27272742 TI - How Does Stigma Affect People Living with HIV? The Mediating Roles of Internalized and Anticipated HIV Stigma in the Effects of Perceived Community Stigma on Health and Psychosocial Outcomes. AB - Few researchers have attempted to examine the mechanisms through which HIV related stigma in the community is processed and experienced at an individual level by people living with HIV. We examined how the effects of perceived HIV stigma in the community on health outcomes for people living with HIV are mediated by internalized stigma and anticipated stigma. Participants (N = 203) from an HIV clinic completed self-report measures and their clinical data were obtained from medical records. Results suggested that the association between perceived community stigma and affective, cognitive, and mental health outcomes (self-esteem, depressive symptoms, avoidance coping, self-blame) are mediated by internalized stigma. Furthermore, a serial mediation model suggested that perceived community stigma leads to internalized stigma, which leads to anticipated community stigma, which in turn leads to lower medication adherence. The associations between perceived community stigma and interpersonal outcomes (social support, trust in physicians) were mediated by internalized stigma and anticipated stigma, again in a serial fashion (perceived community stigma leads to internalized stigma, which leads to anticipated stigma, which in turn leads to interpersonal outcomes). These results suggest that perceived HIV-related stigma in the community may cause people living with HIV to internalize stigma and anticipate stigmatizing experiences, resulting in adverse health and psychosocial outcomes-information that can be used to shape interventions. PMID- 27272744 TI - Local cascades induced global contagion: How heterogeneous thresholds, exogenous effects, and unconcerned behaviour govern online adoption spreading. AB - Adoption of innovations, products or online services is commonly interpreted as a spreading process driven to large extent by social influence and conditioned by the needs and capacities of individuals. To model this process one usually introduces behavioural threshold mechanisms, which can give rise to the evolution of global cascades if the system satisfies a set of conditions. However, these models do not address temporal aspects of the emerging cascades, which in real systems may evolve through various pathways ranging from slow to rapid patterns. Here we fill this gap through the analysis and modelling of product adoption in the world's largest voice over internet service, the social network of Skype. We provide empirical evidence about the heterogeneous distribution of fractional behavioural thresholds, which appears to be independent of the degree of adopting egos. We show that the structure of real-world adoption clusters is radically different from previous theoretical expectations, since vulnerable adoptions induced by a single adopting neighbour-appear to be important only locally, while spontaneous adopters arriving at a constant rate and the involvement of unconcerned individuals govern the global emergence of social spreading. PMID- 27272746 TI - Low-level phototherapy to improve exercise capacity and muscle performance: a systematic review and meta-analysis. AB - The aim of this study was to evaluate the effectiveness of pre-exercise low-level phototherapy (Light-Emitting Diode therapy [LEDtherapy] or Light Amplification by Stimulate Emission of Radiation therapy [LASERtherapy]) in increasing exercise capacity and muscle performance of people undergoing exercise when compared to placebo treatment. Randomized controlled trials and crossover studies were sought on CENTRAL, MEDLINE, EMBASE, SciELO, PEDro and LILACS from its inception up to February 2015. References lists of included studies were sought for additional relevant research. Two authors independently extracted data on study design, treatment parameters, exercise capacity (number of repetitions, time to exhaustion, blood lactate concentration and lactate dehydrogenase activity) and muscle performance (torque, power and strength) using an structured table. Agreement should be reached by consensus or by a third reviewer. Sixteen studies involving 297 participants were included. Improvement of number of repetitions (mean difference [MD] [95 % confidence interval] = 3.51 repetitions [0.65-6.37]; P = 0.02), delay in time to exhaustion (MD = 4.01 s [2.10-5.91]; P < 0.0001), reduction in lactate levels (MD = 0.34 mmol/L [0.19-0.48]; P < 0.00001) and increased peak torque (MD = 21.51 Nm [10.01-33.01]; P < 0.00001) were observed when LASERtherapy was applied. LEDtherapy meta-analyses were performed with two studies and retrieved no between-group statistically significant difference in power, lactate levels or time to exhaustion. Although our results suggest that LASERtherapy is effective in improving skeletal muscle exercise capacity, the quality of the current evidence is limited. PMID- 27272747 TI - Skin healing and collagen changes of rats after fractional erbium:yttrium aluminum garnet laser: observation by reflectance confocal microscopy with confirmed histological evidence. AB - The fractional erbium:yttrium aluminum garnet (Er:YAG) laser is widely applied. Microstructural changes after laser treatment have been observed with histopathology. Epidermal and dermal microstructures have also been analyzed using reflectance confocal microscopy (RCM). However, no studies have compared these two types of microstructural changes in the same subject at multiple time points after irradiation, and it is unclear if these two types of changes are consistent. We use RCM to observe the effect of different laser energies on skin healing and collagen changes in the skin of Sprague-Dawley rats that had been irradiated by fractional Er:YAG lasering at different energies. RCM was used to observe skin healing and detect collagen changes at different time points. Collagen changes were observed using hematoxylin and eosin (H&E) staining and quantitatively analyzed by western blot. RCM showed that, irrespective of laser energy, microscopic treatment zones (MTZs) were larger at 1 day after irradiation. The MTZs then reduced in size from 3 to 7 days after irradiation. The higher the energy, the larger the MTZ area. The amount of collagen also increased with time from 1 day to 8 weeks. However, the increase in the collagen amount on both RCM and H&E staining was not influenced by the laser energy. Western blotting confirmed that the amount of type I and type III collagens increased over time, but there were no significant differences between the different energy groups (p > 0.05). In conclusion, RCM is a reliable technique for observing and evaluating skin healing and collagen expression after laser irradiation. PMID- 27272749 TI - Physicochemical Profiling of alpha-Lipoic Acid and Related Compounds. AB - Lipoic acid, the biomolecule of vital importance following glycolysis, shows diversity in its thiol/disulfide equilibria and also in its eight different protonation forms of the reduced molecule. In this paper, lipoic acid, lipoamide, and their dihydro derivatives were studied to quantify their solubility, acid base, and lipophilicity properties at a submolecular level. The acid-base properties are characterized in terms of six macroscopic, 12 microscopic protonation constants, and three interactivity parameters. The species-specific basicities, the pH-dependent distribution of the microspecies, and lipophilicity parameters are interpreted by various intramolecular effects, and contribute to understanding the antioxidant, chelate-forming, and enzyme cofactor behavior of the molecules observed. PMID- 27272750 TI - Effect of clinical parameters on the control of myoelectric robotic prosthetic hands. AB - Improving the functionality of prosthetic hands with noninvasive techniques is still a challenge. Surface electromyography (sEMG) currently gives limited control capabilities; however, the application of machine learning to the analysis of sEMG signals is promising and has recently been applied in practice, but many questions still remain. In this study, we recorded the sEMG activity of the forearm of 11 male subjects with transradial amputation who were mentally performing 40 hand and wrist movements. The classification performance and the number of independent movements (defined as the subset of movements that could be distinguished with >90% accuracy) were studied in relationship to clinical parameters related to the amputation. The analysis showed that classification accuracy and the number of independent movements increased significantly with phantom limb sensation intensity, remaining forearm percentage, and temporal distance to the amputation. The classification results suggest the possibility of naturally controlling up to 11 movements of a robotic prosthetic hand with almost no training. Knowledge of the relationship between classification accuracy and clinical parameters adds new information regarding the nature of phantom limb pain as well as other clinical parameters, and it can lay the foundations for future "functional amputation" procedures in surgery. PMID- 27272748 TI - Cohort study of electronic cigarette use: effectiveness and safety at 24 months. AB - OBJECTIVE: To evaluate the safety and effectiveness of e-cigarettes, by comparing users of only e-cigarettes, smokers of only tobacco cigarettes and dual users. DESIGN: Prospective cohort study. We update previous 12-month findings and report the results of the 24-month follow-up. DATA SOURCES: Direct contact and questionnaires by phone or via internet. METHODS: Adults (30-75 years) were classified as: (1) tobacco smokers, if they smoked >=1 tobacco cigarette/day, (2) e-cigarette users, if they inhaled >=50 puffs/week of any type of e-cigarette and (3) dual users, if they smoked tobacco cigarettes and also used e-cigarettes. Carbon monoxide levels were tested in 50% of those declaring tobacco smoking abstinence. Hospital discharge data were used to validate possibly related serious adverse events in 46.0% of the sample. MAIN OUTCOME MEASURES: Sustained abstinence from tobacco cigarettes and/or e-cigarettes after 24 months, the difference in the number of tobacco cigarettes smoked daily between baseline and 24 months, possibly related serious adverse events. RESULTS: Data at 24 months were available for 229 e-cigarette users, 480 tobacco smokers and 223 dual users (overall response rate 68.8%). Of the e-cigarette users, 61.1% remained abstinent from tobacco (while 23.1% and 26.0% of tobacco-only smokers and dual users achieved tobacco abstinence). The rate (18.8%) of stopping use of either product (tobacco and/or e-cigarettes) was not higher for e-cigarette users compared with tobacco smokers or dual users. Self-rated health and adverse events were similar between all groups. Among those continuing to smoke, there were no differences in the proportion of participants reducing tobacco cigarette consumption by 50% or more, the average daily number of cigarettes and the average self-rated health by baseline group. Most dual users at baseline abandoned e-cigarettes and continued to smoke tobacco. Those who continued dual using or converted from tobacco smoking to dual use during follow-up experienced significant improvements in the 3 outcomes compared with those who continued or switched to only smoking tobacco (p<0.001). CONCLUSIONS: E-cigarette use alone might support tobacco quitters remaining abstinent from smoking. However, dual use did not improve the likelihood of quitting tobacco or e-cigarette use, but may be helpful to reduce tobacco consumption. Adverse event data were scarce and must be considered preliminary. TRIAL REGISTRATION NUMBER: NCT01785537. PMID- 27272752 TI - Transposon-mediated random gene disruption with moderate halophilic bacteria and its application for halophilic bacterial siderophore analysis. AB - Analytical conditions using chromo azurol S was validated for quantification of siderophore in aqueous samples, followed by the characterization of siderophore derived from newly isolated moderately halophilic bacteria. Conditions with good linearity between the absorbance and the siderophore concentration were obtained at a siderophore concentration less than 20 uM, in the wavelength range between 630 and 660 nm with developing time for at least 2 h. Of the halophilic bacteria isolated from Tunisian soil, Halomonas sp., namely strain 21a was selected as siderophore producing halophiles. The strain produced siderophore significantly in the absence of iron in minimal medium. Siderophore-deficient mutant, namely IIa10, of the strain 21a was obtained from gene disruptant library constructed using transposon complex by electroporation. Genomic sequence analysis of the mutant IIa10 revealed that the transposon-inserted gene was TonB-dependent receptor. PMID- 27272751 TI - In situ effects of metal contamination from former uranium mining sites on the health of the three-spined stickleback (Gasterosteus aculeatus, L.). AB - Human activities have led to increased levels of various pollutants including metals in aquatic ecosystems. Increase of metallic concentrations in aquatic environments represents a potential risk to exposed organisms, including fish. The aim of this study was to characterize the environmental risk to fish health linked to a polymetallic contamination from former uranium mines in France. This contamination is characterized by metals naturally present in the areas (manganese and iron), uranium, and metals (aluminum and barium) added to precipitate uranium and its decay products. Effects from mine releases in two contaminated ponds (Pontabrier for Haute-Vienne Department and Saint-Pierre for Cantal Department) were compared to those assessed at four other ponds outside the influence of mine tailings (two reference ponds/department). In this way, 360 adult three-spined sticklebacks (Gasterosteus aculeatus) were caged for 28 days in these six ponds before biomarker analyses (immune system, antioxidant system, biometry, histology, DNA integrity, etc.). Ponds receiving uranium mine tailings presented higher concentrations of uranium, manganese and aluminum, especially for the Haute-Vienne Department. This uranium contamination could explain the higher bioaccumulation of this metal in fish caged in Pontabrier and Saint-Pierre Ponds. In the same way, many fish biomarkers (antioxidant and immune systems, acetylcholinesterase activity and biometric parameters) were impacted by this environmental exposure to mine tailings. This study shows the interest of caging and the use of a multi-biomarker approach in the study of a complex metallic contamination. PMID- 27272753 TI - Personalized nutrition diagnostics at the point-of-need. AB - Micronutrient deficiency is widespread and negatively impacts morbidity, mortality, and quality of life globally. On-going advancements in nutritional biomarker discovery are enabling objective and accurate assessment of an individual's micronutrient and broader nutritional status. The vast majority of such assessment however still needs to be conducted in traditional centralized laboratory facilities which are not readily accessible in terms of cost and time in both the developed and developing countries. Lab-on-a-chip (LOC) technologies are enabling an increasing number of biochemical reactions at the point-of-need (PON) settings, and can significantly improve the current predicament in nutrition diagnostics by allowing rapid evaluation of one's nutritional status and providing an easy feedback mechanism for tracking changes in diet or supplementation. We believe that nutrition diagnostics represents a particularly appealing opportunity over other PON applications for two reasons: (1) healthy ranges for many micronutrients are well defined which allows for an unbiased diagnosis, and (2) many deficiencies can be reversed through changes in diet or supplementation before they become severe. In this paper, we provide background on nutritional biomarkers used in nutrition diagnostics and review the emerging technologies that exploit them at the point-of-need. PMID- 27272754 TI - IGF-1 and Chondroitinase ABC Augment Nerve Regeneration after Vascularized Composite Limb Allotransplantation. AB - Impaired nerve regeneration and inadequate recovery of motor and sensory function following peripheral nerve repair remain the most significant hurdles to optimal functional and quality of life outcomes in vascularized tissue allotransplantation (VCA). Neurotherapeutics such as Insulin-like Growth Factor-1 (IGF-1) and chondroitinase ABC (CH) have shown promise in augmenting or accelerating nerve regeneration in experimental models and may have potential in VCA. The aim of this study was to evaluate the efficacy of low dose IGF-1, CH or their combination (IGF-1+CH) on nerve regeneration following VCA. We used an allogeneic rat hind limb VCA model maintained on low-dose FK506 (tacrolimus) therapy to prevent rejection. Experimental animals received neurotherapeutics administered intra-operatively as multiple intraneural injections. The IGF-1 and IGF-1+CH groups received daily IGF-1 (intramuscular and intraneural injections). Histomorphometry and immunohistochemistry were used to evaluate outcomes at five weeks. Overall, compared to controls, all experimental groups showed improvements in nerve and muscle (gastrocnemius) histomorphometry. The IGF-1 group demonstrated superior distal regeneration as confirmed by Schwann cell (SC) immunohistochemistry as well as some degree of extrafascicular regeneration. IGF 1 and CH effectively promote nerve regeneration after VCA as confirmed by histomorphometric and immunohistochemical outcomes. PMID- 27272755 TI - (68)Ga-PSMA ligand PET/CT-based radiotherapy in locally recurrent and recurrent oligometastatic prostate cancer : Early efficacy after primary therapy. AB - PURPOSE: The goal of this work was to evaluate the early efficacy of (68)Ga-PSMA ligand PET/CT imaging for radiotherapy of locally recurrent and/or oligometastatic prostate cancer. PATIENTS AND METHODS: A total of 29 patients with biochemical recurrence received a (68)Ga-PSMA ligand PET/CT for restaging of disease, followed by 3D conformal radiotherapy of metastases or intensity modulated radiation therapy of the prostate bed. Prostate-specific antigen (PSA) levels and imaging procedures served as the reference standard to assess the treatment efficacy. RESULTS: PET/CT was positive in 96.6% of patients and revealed that 13.8% of patients had locally recurrent disease, 58.6% had isolated lymph node metastases, 20.7% had isolated bone metastases, and 3.4% showed lymph node metastases and a vertebral metastasis. The median follow-up was 8.3 months (range 3.0-17.3 months). The median PSA prior to radiotherapy was 1.47 ng/ml (range 0.52-32.01 ng/ml) and showed a statistically significant decrease to 0.58 ng/ml (range < 0.07 to 6.33 ng/ml, p < 0.001). Two patients (6.8%) developed progressive disease outside the radiation field after 12.0 and 12.7 months, yielding a local control rate of 100% at the median follow-up. No grade III acute toxicity or late toxicity grade II was observed. Only 2 patients (6.8%) reported persisting grade I diarrhoea according to the LENT-SOMA criteria 3 months after radiotherapy. Deterioration of the urinary or faecal continence was not observed. CONCLUSION: Preliminary results in the presented cohort suggest that radiotherapy based on (68)Ga-PSMA ligand PET/CT yields effective local control and significant treatment response in terms of PSA levels in the absence of clinically important side effects. Furthermore, this approach delayed the necessity of androgen deprivation therapy or systemic therapy. PMID- 27272757 TI - Surgery in Italy. Criteria to identify the hospital units and the tertiary referral centers entitled to perform it : A proposal for esophageal, hepatic, pancreatic and colo-rectal surgery. PMID- 27272756 TI - Long-term survival following additive radiotherapy in patients with atypical teratoid rhabdoid tumors. AB - BACKGROUND: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive disease of embryonic origin accounting for <5% of all pediatric central nervous system (CNS) tumors. PATIENTS AND METHODS: We describe a series of five cases of CNS ATRT. The first three patients underwent subtotal tumor resection. Gross total resection of the tumor was achieved in the fourth and fifth patients. Only 4 patients received chemotherapy, whereas all 5 patients received additive radiotherapy (RT). The latter included three dimensional (3D) conformal RT or intensity modulated RT (IMRT) with a median dose of 54 Gy (range 50.4-59.0 Gy) applied in daily fractions of 1.8 Gy. The median interval between surgery and RT was 5 months (range 2-11 months). RESULTS: Two months after completion of RT, 4 patients had achieved complete radiologic remission. The median event-free survival period was 46 months (range 10-90 months). However, the first patient died 17 months after developing an out-of-field recurrence. The third patient developed a recurrence 11 months after salvage RT. The other 3 patients (cases 2, 4, and 5) remain alive with no evidence of disease 59, 46 and 90 months after therapy, respectively. CONCLUSION: Overall, the 5 patients survived for a median of 48 months (range 25-90 months) from the time of initial diagnosis and they tolerated the RT well, without severe acute or late onset toxicities. The results imply a potential survival gain after irradiation at acceptable toxicity level. PMID- 27272758 TI - Erectile function post robotic radical prostatectomy: technical tips to improve outcomes? AB - Robotic surgery is becoming more and more commonplace. At the same time, so are complications, especially related to erectile function. The population being diagnosed with cancer is younger, with more aggressive cancers and higher expectations for good erectile function postoperatively. We conduct a retrospective analysis of literature over 20 years for Embase and Medline. Search terms used include (Robotic) AND (prostatectomy) AND (erectile function). There are a variety of multifactorial causes, resulting in worsening ED post-robotic radical prostatectomy; however, there are a number of treatments that can support this. There is much we can do to help prevent patients getting postoperative erectile dysfunction post-radical surgery. However, part of this is management of realistic patient expectations. PMID- 27272759 TI - Robotic-assisted laparoscopic radical nephrectomy using the Da Vinci Si system: how to improve surgeon autonomy. Our step-by-step technique. AB - Herein, we describe several steps to improve surgeon autonomy during a Left Robotic-Assisted Laparoscopic Radical Nephrectomy (RALRN), using the Da Vinci Si system. Our kidney cancer program is based on 2 community hospitals. We use the Da Vinci Si system. Access is obtained with the following trocars: Two 8 mm robotic, one 8 mm robotic, bariatric length (arm 3), 15 mm for the assistant and 12 mm for the camera. We use curved monopolar scissors in robotic arm 1, Bipolar Maryland in arm 2, Prograsp Forceps in arm 3, and we alternate throughout the surgery with EndoWrist clip appliers and the vessel sealer. Here, we described three steps and the use of 3 robotic instruments to improve surgeon autonomy. Step 1: the lower pole of the kidney was dissected and this was retracted upwards and laterally. This maneuver was performed using the 3rd robotic arm with the Prograsp Forceps. Step 2: the monopolar scissors was replaced (robotic arm 1) with the robotic EndoWrist clip applier, 10 mm Hem-o-Lok. The renal artery and vein were controlled and transected by the main surgeon. Step 3: the superior, posterolateral dissection and all bleeders were carefully coagulated by the surgeon with the EndoWrist one vessel sealer. We have now performed 15 RALRN following these steps. Our results were: blood loss 300 cc, console time 140 min, operating room time 200 min, anesthesia time 180 min, hospital stay 2.5 days, 1 incisional hernia, pathology: (13) RCC clear cell, (1) chromophobe and (1) papillary type 1. Tumor Stage: (5) T1b, (8) T2a, (2) T2b. We provide a concise, step-by-step technique for radical nephrectomy (RN) using the Da Vinci Si robotic system that may provide more autonomy to the surgeon, while maintaining surgical outcome equivalent to standard laparoscopic RN. PMID- 27272760 TI - Universal HbA1c Measurement in Early Pregnancy to Detect Type 2 Diabetes Reduces Ethnic Disparities in Antenatal Diabetes Screening: A Population-Based Observational Study. AB - In response to the type 2 diabetes epidemic, measuring HbA1c with the first antenatal blood screen was recently recommended in NZ. This would enable prompt treatment of women with unrecognised type 2 diabetes, who may otherwise go undetected until the gestational diabetes (GDM) screen. We compare inter-ethnic antenatal screening practices to examine whether the HbA1c test would be accessed by ethnicities most at risk of diabetes, and we determined the prevalence of unrecognised type 2 diabetes and prediabetes in our pregnant population. This is an observational study of pregnancies in Christchurch NZ during 2008-2010. Utilising electronic databases, we matched maternal characteristics to first antenatal bloods, HbA1c, and GDM screens (glucose challenge tests and oral glucose tolerance tests). Overall uptake of the first-antenatal bloods versus GDM screening was 83.1% and 53.8% respectively in 11,580 pregnancies. GDM screening was lowest in Maori 39.3%, incidence proportion ratio (IPR) 0.77 (0.71, 0.84) compared with Europeans. By including HbA1c with the first-antenatal bloods, the number screened for diabetes increases by 28.5% in Europeans, 40.0% in Maori, 28.1% in Pacific People, and 26.7% in 'Others' (majority of Asian descent). The combined prevalence of unrecognised type 2 diabetes and prediabetes by NZ criteria, HbA1c >=5.9% (41mmol/mol), was 2.1% in Europeans, Maori 4.7% IPR 2.59 (1.71, 3.93), Pacific People 9.5% IPR 4.76 (3.10, 7.30), and 'Others' 6.2% IPR 2.99 (2.19, 4.07). Applying these prevalence data to 2013 NZ national births data, routine antenatal HbA1c testing could have identified type 2 diabetes in 0.44% and prediabetes in 3.96% of women. Routine HbA1c measurement in early pregnancy is an ideal screening opportunity, particularly benefitting vulnerable groups, reducing ethnic disparities in antenatal diabetes screening. This approach is likely to have world-wide relevance and applicability. Further research is underway to establish whether, as for type 2 diabetes, prompt treatment of prediabetes improves pregnancy and neonatal outcomes. PMID- 27272762 TI - Blackish haematuria and gas gangrene. PMID- 27272761 TI - Focus on veno-venous ECMO in adults with severe ARDS. PMID- 27272763 TI - Association Between BRCA Status and P53 Status in Breast Cancer: A Meta-Analysis. AB - BACKGROUND Research on BRCA mutation has meaningful clinical implications, such as identifying risk of second primary cancers and risk of hereditary cancers. This study seeks to summarize available data to investigate the association between BRCA status and P53 status by meta-analysis. MATERIAL AND METHODS We searched PubMed, Embase, and Cochrane library databases for relevant studies. Meta-analysis was conducted using STATA software. We summarized odds ratios by fixed-effects or random-effects models. RESULTS This study included a total of 4288 cases from 16 articles, which including 681 BRCA1 mutation carriers (BRCA1Mut), 366 carriers of BRCA2 mutation (BRCA2Mut), and 3241 carriers of normal versions of these genes. BRCA1Mut was significantly associated with P53 over-expression compared with BRCA2Mut (OR 1.851, 95% CI=1.393-2.458) or non carriers (OR=2.503, 95% CI=1.493-4.198). No difference was found between p53 protein expression in BRCA2 Mut carriers and non-carriers (OR=0.881, 95% CI=0.670 1.158). CONCLUSIONS Our meta-analysis suggests that BRCA1Mut breast cancer patients are more likely to have P53 overexpression compared with BRCA2Mut and non-carriers. This information provides valuable information for clinicians who perform related studies in the future. PMID- 27272764 TI - Investigation on Quantitative Structure Activity Relationships of a Series of Inducible Nitric Oxide. AB - A series of 2-dihydro-4-quinazolin with potent highly selective inhibitors of inducible nitric oxide synthase activities was subjected to quantitative structure activity relationships (QSAR) analysis. Statistically significant equations with high correlation coefficient (r 2 = 0.8219) were developed. The k nearest neighbor model has showed good cross-validated correlation coefficient and external validation values of 0.7866 and 0.7133, respectively. The selected electrostatic field descriptors the presence of blue ball around R1 and R4 in the quinazolinamine moiety showed electronegative groups favorable for nitric oxide synthase activity. The QSAR models may lead to the structural requirements of inducible nitric oxide compounds and help in the design of new compounds. PMID- 27272765 TI - The Germ Cell Gene TDRD1 as an ERG Target Gene and a Novel Prostate Cancer Biomarker. AB - BACKGROUND: TMPRSS2-ERG fusion occurs in about half of prostate cancers and results in over-expression of the oncogenic ERG protein in the prostate. The mechanism by which ERG contributes to prostate cancer initiation and progression remains largely unknown. Because ERG is a transcriptional activator, we reasoned that the target genes regulated by ERG could contribute to prostate cancer development. METHODS: In a search for ERG target genes, we took advantage of published datasets from the MSKCC Prostate Oncogene Project, in which a comprehensive analysis was applied to define transcriptomes in 150 prostate tumors. We retrieved the mRNA expression dataset, split them based on ERG expression, and identified genes whose expression levels are associated with ERG mRNA levels. RESULTS: mRNA expression levels of 21 genes were found to be significantly increased, while for one gene it was decreased in ERG-positive prostate tumors. Among them, the expression of TDRD1 was the most significantly increased in ERG-positive tumors. Among 131 primary prostate tumors which were primarily from European American patients, TDRD1 is over-expressed in 68% of samples, while ERG is overexpressed in 48% of samples, suggesting an additional ERG-independent mechanism of TDRD1 overexpression. In African American prostate tumors, TDRD1 mRNA is expressed in 44%, while ERG is expressed in 24% of samples. In normal tissues, TDRD1 mRNA is exclusively expressed in germ cells and its protein is also known as cancer/testis antigen 41.1 (CT41.1). We generated a mouse monoclonal antibody that recognizes human TDRD1 protein with high specificity and sensitivity. By Western blot analysis and immunohistochemistry (IHC) staining, we demonstrate that TDRD1 protein is expressed in the majority of human prostate tumors, but not in normal prostate tissue. Finally, TDRD1 is not induced in the prostate of ERG overexpression transgenic mice, suggesting that such model does not fully recapitulate the TMPRSS2/ERG fusion-dependent human prostate cancer development. CONCLUSIONS: Our results suggest TDRD1 as a novel prostate cancer biomarker. As an ERG target gene, TDRD1 might play an important role in human prostate cancer development, and as a cancer/testis antigen, TDRD1 might have long-term potential to be a therapeutic target for prostate cancer immunotherapy. Prostate 76:1271-1284, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27272766 TI - Estrogen's Effects on Excitatory Synaptic Transmission Entail Integrin and TrkB Transactivation and Depend Upon beta1-integrin function. AB - Estradiol (E2) perfusion rapidly increases the strength of fast excitatory transmission and facilitates long-term potentiation in the hippocampus, two effects likely related to its memory-enhancing properties. Past studies showed that E2's facilitation of transmission involves activation of RhoA signaling leading to actin polymerization in dendritic spines. Here we report that brief exposure of adult male hippocampal slices to 1 nM E2 increases the percentage of postsynaptic densities associated with high levels of immunoreactivity for activated forms of the BDNF receptor TrkB and beta1-integrins, two synaptic receptors that engage actin regulatory RhoA signaling. The effects of E2 on baseline synaptic responses were unaffected by pretreatment with the TrkB-Fc scavenger for extracellular BDNF or TrkB antagonism, but were eliminated by neutralizing antisera for beta1-integrins. E2 effects on synaptic responses were also absent in conditional beta1-integrin knockouts, and with inhibition of matrix metalloproteinases, extracellular enzymes that generate integrin ligands. We propose that E2, acting through estrogen receptor-beta, transactivates synaptic TrkB and beta1-integrin, and via mechanisms dependent on integrin activation and signaling, reversibly reorganizes the spine cytoskeleton and thereby enhances synaptic responses in adult hippocampus. PMID- 27272767 TI - Working Memory Impairing Actions of Corticotropin-Releasing Factor (CRF) Neurotransmission in the Prefrontal Cortex. AB - The prefrontal cortex (PFC) regulates cognitive processes critical for goal directed behavior. PFC cognitive dysfunction is implicated in multiple psychopathologies, including attention deficit hyperactivity disorder (ADHD). Although it has long been known that corticotropin-releasing factor (CRF) and CRF receptors are prominent in the PFC, the cognitive effects of CRF action within the PFC are poorly understood. The current studies examined whether CRF receptor activation in the PFC modulates cognitive function in rats as measured in a delayed response task of spatial working memory. CRF dose-dependently impaired working memory performance when administered either intracerebroventricularly (ICV) or directly into the PFC. The working memory actions of CRF in the PFC were topographically organized, with impairment observed only following CRF infusions into the caudal dorsomedial PFC (dmPFC). Additional studies examined whether endogenous CRF modulates working memory. Both ICV and intra-dmPFC administration of the nonselective CRF antagonist, D-Phe-CRF, dose-dependently improved working memory performance. To better assess the translational potential of CRF antagonists, we examined the cognitive effects of systemic administration of the CRF1 receptor selective antagonist, NBI 35965. Similar procognitive actions were observed in these studies. These results are the first to demonstrate that CRF acts in the PFC to regulate PFC-dependent cognition. Importantly, the ability of CRF antagonists to improve working memory is identical to that seen with all approved treatments for ADHD. These observations suggest that CRF antagonists may represent a novel approach for the treatment of ADHD and other disorders associated with dysregulated prefrontal cognitive function. PMID- 27272769 TI - Relationship Between Hippocampal Volume, Serum BDNF, and Depression Severity Following Electroconvulsive Therapy in Late-Life Depression. AB - Recent structural imaging studies have described hippocampal volume changes following electroconvulsive therapy (ECT). It has been proposed that serum brain derived neurotrophic factor (sBDNF)-mediated neuroplasticity contributes critically to brain changes following antidepressant treatment. To date no studies have investigated the relationship between changes in hippocampal volume, mood, and sBDNF following ECT. Here, we combine these measurements in a longitudinal study of severe late-life unipolar depression (LLD). We treated 88 elderly patients with severe LLD twice weekly until remission (Montgomery-Asberg Depression Rating Scale (MADRS) <10). sBDNF and MADRS were obtained before ECT (T0), after the sixth ECT (T1), 1 week after the last ECT (T2), 4 weeks after the last ECT (T3), and 6 months after the last ECT (T4). Hippocampal volumes were quantified by manual segmentation of 3T structural magnetic resonance images in 66 patients at T0 and T2 and in 23 patients at T0, T2, and T4. Linear mixed models (LMM) were used to examine the evolution of MADRS, sBDNF, and hippocampal volume over time. Following ECT, there was a significant decrease in MADRS scores and a significant increase in hippocampal volume. Hippocampal volume decreased back to baseline values at T4. Compared with T0, sBDNF levels remained unchanged at T1, T2, and T3. There was no coevolution between changes in MADRS scores, hippocampal volume, and sBDNF. Hippocampal volume increase following ECT is an independent neurobiological effect unrelated to sBDNF and depressive symptomatology, suggesting a complex mechanism of action of ECT in LLD. PMID- 27272771 TI - Management of Metastatic Bone Disease Algorithms for Diagnostics and Treatment. AB - BACKGROUND: Bone is a frequent site of metastases in advanced cancer and is associated with significant skeletal morbidity. Current treatment options are aimed at preserving and improving functional independence and quality of life. MATERIALS AND METHODS: A review of current literature focusing on diagnostic tools and treatment approaches of bone metastasis in advanced cancer was performed and conclusions were incorporated into diagnostic and treatment algorithms. RESULTS: Radiologic imaging has added valuable tools for screening and diagnostics of bone metastasis. Clinical management of skeletal metastasis includes improved pain management, introduction of bone modifying agents and advancements in surgical and radiation therapy. We propose three algorithms enhancing the sensitivity of diagnostics and improving multidisciplinary management of vertebral and non-vertebral bone metastasis. CONCLUSION: Bone metastases are an expression of a systemic disease. Treatment options include highly specialized modalities yet need to be tailored to individual needs. Algorithms help standardize treatment procedures and can improve treatment outcome in a multidisciplinary setting. PMID- 27272768 TI - Glutamatergic Metabolites, Volume and Cortical Thickness in Antipsychotic-Naive Patients with First-Episode Psychosis: Implications for Excitotoxicity. AB - Neuroimaging studies investigating patients with schizophrenia often report appreciable volumetric reductions and cortical thinning, yet the cause of these deficits is unknown. The association between subcortical and cortical structural alterations, and glutamatergic neurometabolites is of particular interest due to glutamate's capacity for neurotoxicity; elevated levels may be related to neuroanatomical compromise through an excitotoxic process. To this end, we explored the relationships between glutamatergic neurometabolites and structural measures in antipsychotic-naive patients experiencing their first non-affective episode of psychosis (FEP). Sixty antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls underwent a magnetic resonance imaging session, which included a T1-weighted volumetric image and proton magnetic resonance spectroscopy in the precommissural dorsal caudate. Group differences in precommissural caudate volume (PCV) and cortical thickness (CT), and the relationships between glutamatergic neurometabolites (ie, glutamate+glutamine (Glx) and glutamate) and these structural measures, were examined. PCV was decreased in the FEP group (p<0.001), yet did not differ when controlling for total brain volume. Cortical thinning existed in the FEP group within frontal, parietal, temporal, occipital, and limbic regions at a 5% false discovery rate. Glx levels were negatively associated with PCV only in the FEP group (p=0.018). The observed relationship between Glx and PCV in the FEP group is supportive of a focal excitotoxic mechanism whereby increased levels of glutamatergic markers are related to local structural losses. This process may be related to the prominent structural deficits that exist in patients with schizophrenia. PMID- 27272770 TI - Genotype-dependent effect of exogenous 24-epibrassinolide on chromium-induced changes in ultrastructure and physicochemical traits in tobacco seedlings. AB - Greenhouse hydroponic experiments were carried out using three different heavy metal accumulation tobacco genotypes to evaluate how different genotypes responded to chromium (Cr) toxicity in the presence of 24-epibrassinolide (EBR; a biologically active brassinosteroid). The results showed that Cr stress caused a marked reduction in plant biomass, chlorophyll content, chlorophyll fluorescence, and photosynthesis parameters but induced malondialdehyde accumulation and ultrastructure damage, with 2010-38 (L) less affected. Foliar application of 24 epibrassinolide (0.1 MUM) on Cr-stressed plants greatly alleviated Cr-induced inhibition of growth and photosynthesis, oxidative stress and ultrastructure damage, decreased Cr accumulation in different parts of leaves and roots, with the exception of the upper and lower of leaves of genotype L, and maintained ion homeostasis. Regarding genotypes, L was more tolerant than M and H, as it absorbed less Cr and also performed better in all of the studied parameters. These findings suggest a potential role for 24-epibrassinolide in Cr stress alleviation and the utilization of elite genetic resources in future breeding programs to develop low Cr accumulation genotypes. These results advocate a positive role for 24-epibrassinolide in reducing pollutant residues from health point of view. PMID- 27272772 TI - Imaging of Gastrointestinal Stromal Tumors: From Diagnosis to Evaluation of Therapeutic Response. AB - Once considered an obscure tumor entity with poor prognosis, gastrointestinal stromal tumors (GISTs) are nowadays recognized as the most common mesenchymal tumors of the alimentary tract. GISTs differ from other mesenchymal neoplasms at pathology since 90% of them exhibit strong immunohistochemical staining for KIT, a tyrosinase kinase growth factor receptor. In the early 2000s, the ability of imatinib mesylate, a tyrosine kinase inhibitor, to inhibit KIT established a new paradigm for cancer treatment. A reduction in lesion size may not be observed or may appear many months after therapy; thus, tumor response criteria alternative to the Response Evaluation Criteria in Solid Tumors were developed. This review highlights the role of imaging in the detection, characterization, preoperative staging, postoperative assessment, therapy-response evaluation and treatment related toxicities. All this information is crucial in optimizing patient management. Contrast-enhanced computed tomography is the most commonly used modality for staging the disease and assessing treatment response, whereas positron-emission tomography adds valuable functional information. Magnetic resonance imaging (MRI) may also be useful, especially in ano-rectal GISTs. Diffusion-weighted MRI may provide promising indicators of tumor response to targeted molecular therapy. Radiologists and oncologists should be aware of all these issues related to GISTs, since multidisciplinary teams gathering different expertise are usually needed to properly treat patients with GISTs. PMID- 27272773 TI - Birinapant (TL32711) Improves Responses to GEM/AZD7762 Combination Therapy in Triple-negative Breast Cancer Cell Lines. AB - BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer currently lacking targeted therapies. Our previous work demonstrated a therapeutic synergism with gemcitabine (GEM) and the CHK1 inhibitor (AZD7762) combination treatment in a TNBC cell line. We hypothesized that the response to this combination therapy would differ among heterogeneous TNBC patients and that addition of a SMAC mimetic (TL32711) could improve efficacy. MATERIALS AND METHODS: Therapeutic responses to GEM, GEM/AZD7762, and GEM/AZD7762/TL32711 combinations were investigated by XTT assays and western blotting of cell cycle and apoptosis-related proteins in ten TNBC cell lines. RESULTS: TNBC cell lines harboring low levels of endogenous CHK1, cIAP1 and cIAP2 were responsive to GEM alone, whereas cell lines demonstrating a minimal increase in phospho-S345 CHK1 after treatment were responsive to GEM/AZD7762 or GEM/AZD7762/TL32711 combination. CONCLUSION: The response of TNBC cells to particular therapies varies and will require development of predictive biomarkers. PMID- 27272774 TI - Decreased Expression of Retinoid X Receptors During Human and Azoxymethane induced Colorectal Carcinogenesis in the Rat. AB - BACKGROUND/AIM: The family of retinoid X receptors (RXRs) including RXRalpha, beta and gamma, is involved in regulating cell proliferation, differentiation, apoptosis and development. MATERIALS AND METHODS: In order to characterize the role of RXRs during colorectal carcinogenesis, the expression of RXRs in human and azoxymethane (AOM)-induced rat colorectal tumors was profiled by immunohistochemistry. RESULTS: Both human and rat normal colorectal epithelia and hyperplasia exhibited strong nuclear, but weak cytoplasmic staining for all three proteins. Expression of RXRalpha, beta and gamma was significantly reduced in rat carcinomas compared to high-grade dysplasia whether in aberrant crypt foci or in adenomas. All three proteins displayed dramatically reduced nuclear expression in both human adenomas and carcinomas. Reduced expression of RXRalpha and RXRgamma seems more significant than RXRbeta in both human and rat carcinomas. CONCLUSION: Reduced expression of RXRs is associated with colorectal carcinogenesis in both humans and AOM-treated rats. PMID- 27272775 TI - Induction of Apoptosis by Functionalized Fullerene-based Sonodynamic Therapy in HL-60 cells. AB - Ultrasound has been widely utilized for medical diagnosis and therapy due to its ability to penetrate deep-seated tissue with less attenuation of energy and minimal undesirable side-effects. Functionalized fullerenes, such as polyhydroxy fullerene (PHF), have attracted particular attention due to their water solubility and potential application in tumor imaging and therapy as carbon nanomaterials. The present study investigated sonodynamically-induced apoptosis using PHF. Cell suspensions were treated with 2-MHz continuous ultrasound in the presence of PHF for 3 min and apoptosis was assessed by cell morphology using confocal microscopy, fragmentation of DNA (ladder pattern after agarose-gel electrophoresis) and caspase-3 activation. Cells were ultrasound-irradiated from the bottom of the culture dishes under the following condition: frequency, 2 MHz; output power, 3 W/cm(2) Electron spin resonance was used to measure reactive oxygen species. The number of apoptotic cells after sonodynamic exposure (ultrasound and PHF) was significantly higher than produced from other treatments, such as ultrasound alone and PHF alone. Furthermore, DNA fragmentation, caspase-3 activation and enhanced 2,2,6,6-tetramethyl-4 piperidinyloxy (4oxoTEMPO) formation were observed in the sonodynamically-treated cells. Histidine, a well-known reactive oxygen scavenger, significantly inhibited sonodynamically-induced apoptosis, caspase-3 activation and 4oxoTEMPO formation. Sonodynamic therapy with PHF induced apoptosis that was characterized by a series of typical morphological features, such as shrinkage of the cell and fragmentation into membrane-bound apoptotic bodies, in HL-60 cells. The significant inhibition of sonodynamically-induced apoptosis, caspase-3 activation, and 4oxoTEMPO formation due to histidine and tryptophan suggests that reactive oxygen species, such as singlet oxygen, are involved in the sonodynamic induction of apoptosis. These findings indicate that PHF-mediated sonodynamic therapy can trigger caspase-dependent apoptosis and oxidative injury, thus possibly playing a vital role in apoptotic signaling cascades. PMID- 27272776 TI - siRNA Targeting of MDR1 Reverses Multidrug Resistance in a Nude Mouse Model of Doxorubicin-resistant Human Hepatocellular Carcinoma. AB - AIM: To investigate the effects of vector-based small interfering RNA (siRNA) targeting MDR1 on the reversal of multidrug resistance in a mouse model of doxorubicin (DOX)-resistant human hepatocellular carcinoma. MATERIALS AND METHODS: Three siRNAs plasmid vectors (MDR1 siRNA1, MDR1 siRNA2 and MDR1 siRNA3) targeting MDR1 were constructed and transfected into DOX-resistant human hepatocellular carcinoma Bel-7402/ADM cells. The expression of MDR1 mRNA and P glycoprotein (P-gp) was detected with RT-PCR and western blotting, respectively. A nude mouse model of DOX-resistance was established with untransfected Bel 7402/ADM or Bel-7402/ADM transfected with MDR1 siRNA (Bel-7402/ADMsi). The nude mice with tumors from untransfected Bel-7402/ADM cells were treated with either saline (Group 1); intravenous DOX (Group 2); or the combination of intra-tumoral MDR1 siRNA and intravenous DOX (Group 3). The nude mice with tumors from Bel 7402/ADMsi cells were treated with intravenous DOX (Group 4). DOX and MDR1 siRNA were administered twice a week at 20 mg/kg/dose and 9.8 mg/kg/dose, respectively. Tumor growth was measured to assess reversal of multidrug resistance by MDR1 siRNA. RESULTS: MDRl mRNA and P-gp expression of Bel-7402/ADM cells was reduced by transfection of three siRNAs with different silencing efficiency (p<0.05). DOX treatment (Group 4) resulted in significant reduction in tumor size in the Bel 7402/ADMsi tumor model (p<0.05), indicating reversal of multidrug resistance in tumor by MDR1 siRNA. However, the combination treatment of intratumoral MDR1 siRNA and DOX (Group 3) showed no significant anti-tumor efficacy in the untransfected Bel-7402/ADM (p>0.05) tumor model, suggesting poor in vivo transfection efficiency of MDR1 siRNA. Analysis of the tumor samples showed the reduced expression level of MDR1 mRNA and P-gp was due to efficacy of MDR1 siRNA. CONCLUSION: In vitro transfection of siRNAs' vectors targeting the MDR1 gene can effectively silence MDR1 mRNA and P-gp expression in DOX-resistant human hepatocellular carcinoma Bel-7402/ADM cells that resulted in reversal of multidrug resistance to DOX in the xenograft tumor model. PMID- 27272777 TI - Heterogeneity of Vascular Endothelial Growth Factor Receptors 1, 2, 3 in Primary Human Colorectal Carcinoma. AB - BACKGROUND: The vascular endothelial growth factor (VEGF) pathway plays an important role in growth and progression of human cancer, including colorectal carcinomas (CRC). The key mediators of VEGF signaling are VEGFR1, VEGFR2, and VEGFR3, part of a family of related receptor tyrosine kinases. The relative expression, activity, or interplay among these receptors may determine the response of CRC patients to anti-angiogenic therapies. MATERIALS AND METHODS: We developed technically sound immunohistochemical (IHC) assays to quantify VEGFR1, 2 and 3, and using a well-annotated CRC tissue microarray (TMA), we carried out comprehensive comparative evaluation of the three VEGFRs in archival primary CRC tissues (n=84). For each TMA core, tumor cell VEGFR1 expression was reported as H score (range=0-300); vascular VEGFR2/VEGFR3 expression was manually scored as the number of receptor-positive tumor stromal vessels. Each case was defined as VEGFR1/ VEGFR2/VEGFR3-negative, low, medium or high. RESULTS: Based on the differential expression of the three VEGFRs, eight VEGFR staining profiles were observed: Triple VEGFR positive (n=12, 14%), VEGFR1 predominant (n=17, 20%), VEGFR2 predominant (n=7, 8%), VEGFR3 predominant (n=1, 1%), VEGFR1/2 predominant (n=39, 46%), VEGFR1/3 predominant (n=2, 2%), VEGFR2/3 predominant (n=3, 4%), and triple-VEGFR-negative (n=3, 4%). CONCLUSION: Herein we demonstrated heterogeneity of expression of VEGFRs in human CRC stromal vessels and tumor cells. The observed VEGFR expression-based subsets of human CRCs may reflect differences in biology of pathologic angiogenesis in primary CRC tissues. Furthermore, the heterogeneity of expression of VEGFRs unraveled in this analysis merits independent validation in larger cohorts of primary and metastatic human CRC tissues and in pertinent experimental models treated with various anti-angiogenic therapies. PMID- 27272778 TI - Identification of ESE1 as a beta-Catenin Binding Protein. AB - BACKGROUND/AIM: beta-Catenin regulates cell-cell adhesion and gene transcription and acts as a master switch that controls proliferation in several types of cancer. ESE1 is an epithelium-restricted transcription factor and its multiple domain structure predicts its interaction with other proteins with diverse cellular functions. Here, for the first time, we report that endogenous beta catenin binds to and co-localizes with endogenous ESE1 in the cytoplasm. MATERIALS AND METHODS: The binding sites were mapped to E26 transformation specific (ETS) domain at carboxyl terminus of ESE1 and N-terminus of beta catenin. RESULTS: We found that C-terminus of ESE1 also binds to alpha-catenin and that ESE1/beta-catenin interaction was abrogated by knockdown of either beta catenin or alpha-catenin. CONCLUSION: The data suggest that interactions between ESE1 and beta-/alpha-catenins might be a mechanism by which the ESE1 protein determines the beta-catenin function and tumorigenesis. PMID- 27272779 TI - Activation of the PERK-eIF2alpha Pathway Is Associated with Tumor-infiltrating Lymphocytes in HER2-Positive Breast Cancer. AB - BACKGROUND: We evaluated endoplasmic reticulum stress and unfolded protein response (UPR) activation, as possible mechanisms for influx of tumor infiltrating lymphocytes (TILs), and the correlation between UPR activation and mammalian target of rapamycin (mTOR) pathway activation. MATERIALS AND METHODS: TILs and the immunohistochemical expression of protein kinase RNA-like endoplasmic reticulum kinase (PERK), phospho-eukaryotic translation initiation factor 2alpha (p-eIF2alpha) and phosphorylated S6 (pS6) were evaluated in 447 human epidermal growth factor receptor 2 (HER2)-positive breast cancer tissues. RESULTS: High expression of PERK, p-eIF2alpha and pS6 was observed in 270 (60.4%), 259 (57.9%), and 187 (41.8%) cases, respectively, and was significantly associated with a high histological grade, high numbers of TILs, peritumoral lymphocytic infiltration, and tertiary lymphoid structures in HER2-positive breast cancer tissues. CONCLUSION: The results suggest endoplasmic reticulum stress and UPR activation as possible mechanisms for the influx of TILs in HER2 positive breast cancer. Evaluation of PERK and p-eIF2alpha expression might be important in identifying targets for cancer therapies in modulating endoplasmic reticulum stress. PMID- 27272780 TI - Expression Pattern of Matrix Metalloproteinase 20 (MMP20) in Human Tumors. AB - BACKGROUND/AIM: Matrix metalloproteinase 20 (MMP20) is a member of the family of matrix metalloproteinases. Under normal conditions the expression of MMP20 is restricted to ameloblasts and odontoblasts. In order to identify a possible expression of MMP20 under pathological conditions, we investigated three major human tumor entities, i.e. colon, breast and lung tumors, on the mRNA and protein level. MATERIALS AND METHODS: Real-time RT-PCR and immunocytochemical analyses of established human tumor cell lines were employed for our study; immunohistochemical analysis was performed on both primary tumors and normal control tissues. RESULTS: MMP20 was identified on both the mRNA and the protein level in breast MCF-7, colon HT-29, and lung A549 cell lines. MMP20 was also detected in primary tumor tissue by immunohistochemistry. CONCLUSION: MMP20 is a new potential candidate for tumor diagnosis or therapy. PMID- 27272781 TI - Anticancer and Immunomodulatory Effects of Lactobacillus plantarum LS/07, Inulin and Melatonin in NMU-induced Rat Model of Breast Cancer. AB - BACKGROUND/AIM: Chemopreventive activity of a new probiotic strain Lactobacillus plantarum LS/07 (PRO) and prebiotic oligofructose-enriched inulin (PRE) in rat mammary carcinogenesis induced by procarcinogen 7,12-dimethylbenz[a]anthracene has been reported before. This study evaluated the anticancer and immunomodulatory efficacy of PRO, PRE, PRO+PRE (PRO/PRE) and combination with melatonin (PRO+PRE+MEL) in a rat model, when breast cancer was induced by a direct-acting carcinogen N-nitroso-N-methylurea (NMU). MATERIALS AND METHODS: Daily administration of PRO (at a dose of 8.4*10(8) colony-forming units (c.f.u.)/rat), PRE (in the diet, 20 g/kg) and MEL (in tap water, 20 mg/l) started 14 days before the first NMU dose and lasted for 16 weeks. RESULTS: Although tumor growth was not altered, a marked decrease in the ratio of high-/low-grade carcinomas and in tumoral Ki-67 expression was found after PRO+PRE treatment; melatonin augmented these effects. PRO+PRE+MEL combination enhanced CD4(+) and CD8(+) T-cell tumor infiltration induced by PRO/PRE and increased CD25(+)FoxP3(+) regulatory T-cells in tumors. CONCLUSION: In mammary carcinogenesis, Lactobacillus plantarum LS/07 and inulin exert prodifferentiating, antiproliferative and immunomodulatory activities, which are significantly amplified by melatonin co-administration. PMID- 27272782 TI - The Difference in Bronchial Patency Between the Sweet and Modified Overfolt Methods at a Deep Site: Current Strategies Are Based on Previous Knowledge. AB - The use of bronchial stapling with automatic stapling devices has become widespread in chest surgery with the growth of video-assisted thoracoscopic surgery. Thus, hand suturing for the bronchus occurs less commonly. Therefore, modern surgeons have fewer opportunities to perform hand suturing, and, as a consequence, there exists lack understanding of this technique compared to earlier generations. We, therefore, examined the difference in bronchial patency between the Sweet and modified Overfolt methods of suturing performed on sacrificed pigs, as shown by bronchoscopy. Bronchoscopy showed stenosis in the residual bronchus using the Sweet method. However, bronchoscopy revealed a favorable patency in the residual bronchus using the modified Overfolt method. We also found similar results in deeper sites. Our findings suggest that the results of the modified Overfolt technique lead to a favorable patency while based on previous knowledge. PMID- 27272783 TI - Novel Tumor-specific Mutations in Receptor Tyrosine Kinase Subdomain IX Significantly Reduce Extracellular Signal-regulated Kinase Activity. AB - BACKGROUND/AIM: The identification of additional therapeutic targets by clinical molecular profiling is necessary to expand the range of molecular-targeted cancer therapeutics. This study aimed to identify novel functional tumor-specific single nucleotide variants (SNVs) in the kinase domain of receptor tyrosine kinases (RTKs), from whole-exome sequencing (WES) data. MATERIALS AND METHODS: SNVs were selected from WES data of multiple cancer types using both cancer-related databases and the index reflecting molecular evolution. Immunoblotting and luciferase assay were performed to assess the function of selected SNVs. RESULTS: Among the seven selected SNVs, two, namely neurotrophic receptor tyrosine kinase 1 (NTRK1) V710A and fms related tyrosine kinase 3 (FLT3) K868N, detected in kinase subdomain IX, were investigated. These SNVs inhibited the autophosphorylation of the respective RTKs, thereby reducing the activity of extracellular signal-regulated kinases. CONCLUSION: RTK subdomain IX is a promising target for the molecular design of kinase inhibitors. PMID- 27272784 TI - Detection and Characterization of Flat Aberrant Crypt Foci (Flat ACF) in the Novel A/J Min/+ Mouse. AB - BACKGROUND/AIM: Flat aberrant crypt foci (flat ACF) and mucin-depleted foci (MDF) have previously been described as preneoplastic colonic lesions. We used the novel A/J Min/+ mouse model, that demonstrates extensive spontaneous colon carcinogenesis to refine the method of detection of flat ACF and further characterize and define them as early lesions by histological examination and comparison with MDF. MATERIALS AND METHODS: Colons were stained with methylene blue (MB) for flat ACF detection and restained with high-iron diamine-alcian blue (HID-AB) for MDF detection. RESULTS: Optimal flat ACF recognition required at least 24 h of storage post-MB staining and adherence to a set of characteristics. The fraction of flat ACF corresponding with MDF was 93%. Flat ACF/MDF displayed the same picture of severe dysplasia, lack of mucus and goblet cells and accumulation of cytoplasmic beta-catenin. CONCLUSION: The easily detectable flat ACF are reliable surface biomarkers of Apc-driven colon carcinogenesis. PMID- 27272785 TI - Antiproliferative Effects of Various Furanoacridones Isolated from Ruta graveolens on Human Breast Cancer Cell Lines. AB - BACKGROUND/AIM: Thanks to its biologically active constituents, Ruta graveolens L. (Rutaceae) is a widely used medicinal plant. In our study, six furanoacridone alkaloids isolated from Ruta graveolens were investigated for their antiproliferative and pro-apoptotic effects on human breast cancer cell lines (MCF-7, MDA-MB-361, MDA-MB-231 and T47D). MATERIALS AND METHODS: The cell lines were pretreated with alkaloid components (rutacridone, isogravacridone chlorine (IGC), gravacridonediol monomethyl ether, gravacridonediol, gravacridonetriol, a 1:1 mixture of gravacridonetriol and - diol monoglucosides) and their antiproliferative effects were determined by the MTT assay. RESULTS: IGC had the most marked effect on cell proliferation of MDA-MB-231 (half maximal inhibitory concentration (IC50)=2.27 MUM). Cell-cycle analysis was applied to quantify the effect of IGC on subpopulations of MDA-MB-231 and MCF-7 cells. It caused a cell cycle disturbance by decreasing the G2/M and G0/G1 and increasing the S phase and the appearance of the subdiploid (sub-G1) population. Hoechst 33258-propidium iodide staining was used to evaluate the morphological changes in IGC-pretreated MDA-MB-231 and MCF-7 cells, revealing the appearance of apoptotic features. IGC was found to cause a modest activation of caspase-3 and -9, but not caspase-8, indicating the activation of an intrinsic apoptotic pathway in MDA-MB-231 cells. CONCLUSIONS: These in vitro findings indicate that furanoacridones are suitable candidates for anticancer drug development. PMID- 27272786 TI - Subtypes of Triple-negative Breast Cancer Cell Lines React Differently to Eribulin Mesylate. AB - BACKGROUND/AIM: Diagnosis of triple-negative breast cancer (TNBC) is associated with adverse prognosis, particularly in cases of chemotherapy resistance. The goal of this analysis was to compare TNBC vs. non-TNBC cell lines and those of distinct TNBC subtypes with regard to sensitivity to eribulin in vitro. MATERIALS AND METHODS: Breast cancer cell lines were subjected to cell-viability assays, apoptosis analyses, migration and invasion experiments, and quantitative real time polymerase chain reaction after exposure to eribulin. RESULTS: Eribulin reduced cell viability in TNBC and non-TNBC cell lines in the sub-nanomolar range. Furthermore, exposure to eribulin induced apoptosis and decreased the rate of migration and invasion. Genes known to induce malignant transformation were differentially expressed after eribulin treatment. CONCLUSION: Eribulin had a strong antiproliferative effect on breast cancer cell lines, although we did not observe a significant difference between TNBC and non-TNBC cell lines with regard to sensitivity to eribulin. PMID- 27272787 TI - HOXB7 Expression is a Novel Biomarker for Long-term Prognosis After Resection of Hepatocellular Carcinoma. AB - BACKGROUND/AIM: Homeobox B7 (HOXB7) gene is involved in various cellular functions. We investigated the clinical significance of HOXB7 expression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: HOXB7 mRNA expression in 103 HCC samples and 58 matched non-cancerous liver tissues were examined by quantitative real-time polymerase chain reaction (qRT-PCR). HOXB7 protein expression was also examined by immunohistochemistry. Gene set enrichment analysis (GSEA) was performed using a public dataset. RESULTS: HOXB7 expression was significantly higher in HCC tissues than in liver parenchyma. Ten-year overall survival (OS) and 5-year recurrence-free survival (RFS) of cases with higher HOXB7 expression were significantly poorer than those with lower HOXB7 expression. HOXB7 expression was significantly associated with larger tumor size and higher rate of biliary invasion and constituted an independent prognostic factor for OS by multivariate analysis. These results were supported by GSEA. CONCLUSION: HOXB7 expression in HCC could be a novel biomarker for long-term prognosis after tumor resection. PMID- 27272788 TI - Novel Midkine Inhibitor iMDK Inhibits Tumor Growth and Angiogenesis in Oral Squamous Cell Carcinoma. AB - Midkine is a heparin-binding growth factor highly expressed in various human malignant tumors. However, its role in the growth of oral squamous cell carcinoma is not well understood. In this study, we analyzed the antitumor effect of a novel midkine inhibitor (iMDK) against oral squamous cell carcinoma. Administration of iMDK induced a robust antitumor response and suppressed cluster of differentiation 31 (CD31) expression in oral squamous cell carcinoma HSC-2 cells and SAS cells xenograft models. iMDK inhibited the proliferation of these cells dose-dependently, as well as the expression of midkine and phospho extracellular signal-regulated kinase in HSC-2 and SAS cells. Moreover, iMDK significantly inhibited vascular endothelial growth factor and induced tube growth of human umbilical vein endothelial cells in a dose-dependent fashion. These findings suggest that midkine is critically involved in oral squamous cell carcinoma and iMDK can be effectively used for the treatment of oral squamous cell carcinoma. PMID- 27272789 TI - Effect of MPS1 Inhibition on Genotoxic Stress Responses in Murine Tumour Cells. AB - BACKGROUND/AIM: The monopolar spindle 1 (MPS1) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To determine the possible relationship between MPS1 inhibition and genotoxic stress responses, herein we examined whether MPS1 inhibition influences cellular susceptibility towards two genotoxic treatments, etoposide and ionizing radiation (IR). MATERIALS AND METHODS: Two murine tumour cell lines, SCCVII and EMT6, were used. The effect of genotoxic treatments with or without two novel MPS1 inhibitors, NMS P715 and AZ3146, on cellular survival, cell-cycle distribution, centrosome status and mitotic catastrophe (MC) was evaluated. RESULTS: MPS1 inhibition sensitized murine tumour cells to etoposide but not to IR. In addition, MPS1 inhibition altered cell-cycle progression and exacerbated centrosome abnormalities, resulting in enhanced MC induced by etoposide but not by IR. CONCLUSION: MPS1 inhibition promotes the etoposide-induced aberrant mitosis and, consequently, the induction of tumour cell death. PMID- 27272790 TI - Estrogen Enhances Malignant Phenotypes in Human Salivary Adenoid Cystic Carcinoma Cells. AB - BACKGROUND/AIM: Adenoid cystic carcinoma (SGC) is a common type of salivary gland cancer (SGC). Surgery is the first treatment choice because chemoradiotherapy is usually not effective. Therefore, new treatment modalities are urgently needed. In this study, it was investigated whether the estrogen axis could be a treatment target or not. MATERIALS AND METHODS: Adenoid cystic carcinoma (ACC) ACCM cells, were used. The specific cell line lacks estrogen receptor (ER). ER was introduced in ACCM cells, and the effect of 17beta-estradiol (E2) was investigated on cell proliferation, cell-cycle distribution, and cell motility. RESULTS: E2 induced cell proliferation, and the S-phase fraction increased in a dose-dependent manner. Cell motility was also up-regulated compared to control cells. CONCLUSION: The estrogen/ER system up-regulated malignant phenotypes in ER positive ACC, and hormone therapy may have a potential as effective treatment for this malignancy. PMID- 27272791 TI - Targeted Therapies in HPV-positive and -negative HNSCC - Alteration of EGFR and VEGFR-2 Expression In Vitro. AB - BACKGROUND: Angiogenesis plays a crucial role in the formation and progression of tumor growth in head and neck squamous cell carcinoma (HNSCC). The tyrosine kinase receptors epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are essential for mediation of pro-angiogenic signals. Nilotinib, dasatinib, erlotinib and gefitinib are tyrosine kinase inhibitors and approved as targeted therapies for several tumor entities other than HNSCC. In this study, we sought to evaluate the alteration of EGFR and VEGFR 2 expression by these tyrosine kinase inhibitors with respect to the human papillomavirus (HPV)-status in squamous cell carcinoma (SCC) tumor cells. MATERIALS AND METHODS: Expression patterns of EGFR and VEGFR-2 were determined by enzyme linked immunosorbent assay (ELISA) in HNSCC 11A, HNSCC 14C and p-16 positive CERV196 tumor cell lines. These cells were incubated with nilotinib, dasatinib, erlotinib and gefitinib (5-20MUmol/l) and compared to a chemonaive control. The incubation time was 24, 48, 72 and 96 h. RESULTS: All tested substances led to a statistically significant reduction (p<0.05) of EGFR protein expression levels in HPV-negative cells compared to the negative control. Surprisingly, a statistically significant increase in VEGFR-2 expression was observed after exposure to all tested substances especially after exposure to erlotinib treatment. CONCLUSION: Nilotinib, dasatinib, erlotinib and gefitinib cause significant changes in protein expression of EGFR and VEGFR-2 in vitro. Besides the anti-angiogenic impact of the substances, as shown for the decrease of EGFR expression, we also observed an increase of VEGFR-2 expression. These contradictive effects could be interpreted as a compensatory up-regulation by the tumor cell. PMID- 27272792 TI - Synthesis of tris(quinoline)monochloroplatinum(II) Chloride and its Activity Alone and in Combination with Capsaicin and Curcumin in Human Ovarian Cancer Cell Lines. AB - Currently used platinum drugs fail to provide long-term cure for ovarian cancer mainly because of acquired drug resistance. With the idea that the difference may translate into an altered spectrum of activity, monofunctional planaramineplatinum(II) complex tris(quinoline)monochloro-platinum chloride (coded as LH5) was synthesized and investigated for its activity against human ovarian A2780, cisplatin-resistant A2780 (A2780(cisR)) and ZD0473-resistnat A2780 (A2780(ZD0473R)) cancer cell lines alone and in combination with the phytochemicals capsaicin (Caps) and curcumin (Cur) as a function of concentration and sequence of administration. Cell viability was quantified using the MTT reduction assay, while combination was used as a quantitative measure of the combined drug action. LH5 is found to be more active than cisplatin (CS) against both resistant cell lines. Combination of LH5 with capsaicin showed synergism in all three cell lines, with the bolus being most synergistic. Lack of association between the levels of platinum accumulation and platinum-DNA with cytotoxicity can be seen to indicate that binding with DNA may not be the main determinant of activity of LH5. Greater activity of LH5 compared to cisplatin, especially against the resistant cell lines, indicates that the compound may have the potential for development as a novel anticancer drug and that its combination with phytochemicals can serve to further enhance drug efficacy. PMID- 27272793 TI - Histone Deacetylase-1-mediated Suppression of FAS in Chemoresistant Ovarian Cancer Cells. AB - BACKGROUND: Loss of FAS expression in ovarian cancer cells has recently been associated with resistance to chemotherapeutic drugs. However, the mechanism for suppression of FAS expression is unknown. MATERIALS AND METHODS: The cell surface and transcript expressions of death receptors in parental chemosensitive (A2780) and their derivative chemoresistant (A2780-AD) ovarian cancer cells were determined by flow cytometry and quantitative real-time polymerase chain reaction, respectively. The epigenetic regulation of FAS promoters in both A2780 and A2780-AD ovarian epithelial cells were determined by chromatin immunoprecipitation assays. CONCLUSION: This study demonstrated that expression of FAS is suppressed in A2780-AD cells compared to parental A2780 ovarian cells. No difference in DNA methylation was observed at FAS promoters between A2780-AD cells compared to parental cells. However, the level of acetylated histone H3 associated with FAS promoter in A2780-AD cells was significantly lower compared to parental cells, and there was a corresponding increase in histone deacetylase 1 (HDAC1) enzyme associated with the FAS promoter in resistant cells. Knockdown of HDAC1 expression, and pharmacological inhibition of HDAC enzymatic activity significantly increased FAS expression in resistant A2780-AD cells. These results suggest that epigenetic changes in histone modifications may contribute to the loss of FAS expression in chemoresistant ovarian cancer cells and that enhancement of FAS expression could increase tumor cell sensitivity to immune cells. PMID- 27272794 TI - Bendamustin-Rituximab Combination Is a Safe and Effective, Ambulatory Treatment for Elderly Patients with Chronic Lymphocytic Leukemia: Retrospective Real-world Analysis by Age from a German Registry and Review of the Literature. AB - BACKGROUND: Treatment recommendations in chronic lymphocytic leukemia (CLL) are based upon selected, otherwise healthy study populations mostly under 72 years of age. The Project group Internistic Oncology (PIO) embarked on an analysis of the 'real-world' safety and efficacy of bendamustine with and without rituximab in unselected outpatients. PATIENTS AND METHODS: A multicenter, open-label, prospectively stratified, retrospective study was conducted to determine routine feasibility, toxicity, and response rates obtained by bendamustine with and without rituximab in a random population of mostly elderly patients with CLL. Records were obtained from 775 patients with CLL from 60 private medical oncology practices. Informed consent was obtained prior to study participation. The median observation time was 28 months. Patients were stratified according to age, and treatment. Response criteria and statistics followed international guidelines adopted by the "German Chronic Lymphocytic Leukemia Study Group". RESULTS: Overall, 57.5% of patients were over 70 (range=36-95) years old. Eastern Cooperative Oncology Group performance status and age influenced the total dose given, decreasing by 20% between ECOG 0 and 3, and by 15% above 80 years old. Response rates did not differ between the ages of 60 to 80 years, with an overall remission rate for bendamustine of 83%, and for the combination therapy of 89%, decreasing above the age of 80 years. Febrile neutropenia occurred in 25% of 775 patients, and grade 3 or 4 non-hematological adverse events in 9.55% (n=74), not interfering with the treatment. CONCLUSION: Bendamustine with and without rituximab was associated with high activity and tolerability, irrespective of age and risk factors. The median overall survival was 64 months with a 3-year survival rate of 72%; progression-free survival was 30.6 months, and the 3 year PFS was 43%. The good tolerability and feasibility of bendamustine with and without rituximab, in particular for the elderly population with CLL argues for it being a safe outpatient treatment. PMID- 27272795 TI - Expression of Estrogen Receptors in Relation to Hormone Levels and the Nottingham Prognostic Index. AB - BACKGROUND: Estrogen hormones have a large impact on both normal development and tumorigenesis of the breast. MATERIALS AND METHODS: Breast tissue samples from 49 women undergoing surgery were included. The estrogen receptors (ERalpha and ERbeta), ERalpha36 and G-coupled estrogen receptor-1 (GPER) were determined in benign and malignant breast tissue. RESULTS: The ERalpha36 and ERalpha mRNA levels were highest in malignant tumors. Stromal ERbeta immunostaining in benign tumors was higher than in the paired normal tissue. GPER expression was lowest in benign tumors. In the malignant tumors, the Nottingham Prognostic Index (NPI) correlated positively with stromal GPER and the serum testosterone level. The serum insulin-like growth factor-1 (IGF-1) level correlated negatively with GPER mRNA and glandular ERalpha. CONCLUSION: The expression of ERalpha36 is stronger in malignant breast tissue. The strong positive correlation between NPI and GPER in malignant breast stroma indicates an important role for GPER in breast cancer prognosis. PMID- 27272796 TI - Self-reported Symptoms to Monitor Recurrent Head and Neck Cancer-Analysis of 1,678 Cases. AB - AIM: The aim of this article was to study the clinical significance of subjective symptoms of recurrence in patients treated for primary head and neck cancer. MATERIALS AND METHODS: Clinical data of 1,678 patients with squamous cell carcinoma of the head and neck admitted at the Department of Oto-rhino laryngology-Head and Neck Surgery, Oslo University Hospital during a period of 15 years (1983-1997) were analyzed. RESULTS: A total of 525 (31%) patients had recurrence during follow-up, 74% of these within the first two years after primary treatment. Subjective symptoms indicating recurrent disease were reported by 67%. The remaining recurrences were detected in asymptomatic patients at scheduled consultations. Prognosis was better among patients with subjective symptoms of recurrent disease after treatment for primary tumors of the oral cavity and larynx. Those with recurrence from other tumor sites had no difference in prognosis between symptomatic and asymptomatic patients. CONCLUSION: The high proportion of patients with subjective symptoms indicates that there is a potential to make follow-up routines more effective. Individualized and flexible procedures, taking into account patient's self-reported symptoms, may help speed up the process and thus improve prognosis. This could also lead to a more efficient use of resources by reducing the number of redundant examinations of low-risk patients. PMID- 27272797 TI - Pancreatic-type Acinar Cell Carcinoma of the Stomach Included in Multiple Primary Carcinomas. AB - BACKGROUND/AIM: Pancreatic-type acinar cell carcinoma (ACC) in the stomach is extraordinarily rare. We pathologically examined two cases with multiple primary carcinomas, including gastric tumors. PATIENTS AND METHODS: Gastric cancer specimens were examined by immunostaining and electron microscopy. RESULTS: Both cases had cancer cells with acinar patterns, resembling pancreatic ACC. The cancer cells in the first case were positive for exocrine markers, including chymotrypsin, lipase and alpha-1 antichymotrypsin (ACT), as well as neuroendocrine markers, including chromogranin A and synaptophysin. The cancer cells in the second case were positive for chymotrypsin and alpha-1 ACT, while being slightly positive for chromogranin A and synaptophysin. Ultrastructurally, cancer cells contained zymogen granules in both cases. The final diagnosis was pancreatic mixed acinar-neuroendocrine carcinoma and pure pancreatic ACC, respectively. CONCLUSION: We confirmed two cases with gastric pancreatic-type ACC included in multiple primary carcinomas. This type of double cancer has not been reported previously. PMID- 27272798 TI - Oncologic Impact of Renal Tissue Adjacent to Renal Cell Carcinoma. AB - AIM: The aim of the study was to investigate the clinical impact of the surgical margin width after nephron-sparing surgery (NSS) on the oncological course of renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised of 126 RCC patients with NSS between 2002 and 2009. Inclusion criteria were negative resection margins and a tumor diameter of <=100 mm with the possibility of a complete circumferential histopathological reevaluation. The minimal benign margin width was correlated to the patients' clinical course. RESULTS: Median safety margin width was revealed to be 1 mm. Nine of 126 patients (7.1%) developed recurrent disease (five local, four distant). All patients with local recurrence had safety margins <=1 mm, whereas out of 49 patients with a margin >1 mm no one developed local recurrence (p=0.0245). Safety margin <=1 mm showed associations with increased risk for overall recurrence in univariate and multivariate analysis (p=0.0531 and 0.0539, respectively). CONCLUSION: Tumor adjacent renal parenchyma may have oncological relevance, corroborating the need for further molecular investigation of tumor-adjacent tissue in RCC. PMID- 27272799 TI - Diagnostic and Prognostic Value of ProEx C and GLUT1 in Melanocytic Lesions. AB - BACKGROUND: Melanoma is one of the most aggressive types of skin cancer. The purpose of this study was to evaluate the use of two biomarkers, ProEx C and glucose transporter isoform 1 (GLUT1), in the diagnosis and prognostication of melanoma. MATERIALS AND METHODS: We analyzed 129 melanomas and 59 benign nevi in a tissue microarray using immunohistochemical method with antibodies to topoisomerase IIalpha (TOP2A) and minichromosome maintenance complex component 2 (MCM2) using ProEx C and to GLUT1. RESULTS: The average proliferative index by ProEx C immunostain was significantly higher in melanomas (37.5%) compared to benign nevi (1.9%) as was the expression of GLUT1 (p<0.0001 respectively). Dermal mitosis was found to correlate positively with both ProEx C and GLUT1 (p=0.003 and p<0.001, respectively). Ulceration and tumor thickness positively correlated with GLUT1 expression (p=0.013 and p=0.033, respectively), but not with ProEx C staining. There was a significant association between increasing ProEx C index and stronger expression of GLUT1 (p<0.001). Kaplan-Meier disease-specific survival analyses indicated that patients whose melanoma exhibited expression of GLUT1 had a significantly lower rate of disease-specific survival than patients whose melanoma did not (p=0.039). However, staining by ProEx C did not show a prognostic significance in disease-specific survival. CONCLUSION: ProEx C and GLUT1 are potentially useful markers in differentiation of melanoma from nevi. Absence of GLUT1 expression in patients with primary melanoma predicts better survival. PMID- 27272800 TI - Phase II Trial of Erlotinib in Elderly Patients with Previously Treated Non-small Cell Lung Cancer: Results of the Lung Oncology Group in Kyushu (LOGiK-0802). AB - BACKGROUND: As the incidence of lung cancer in the elderly is increasing worldwide, there exists a need to develop a clinically effective, less toxic therapy for this patient population. Although erlotinib has shown proven effectiveness against non-small cell lung cancer (NSCLC), few studies have prospectively investigated its application to elderly patients. PATIENTS AND METHODS: Patients aged >=75 years with advanced or recurrent NSCLC including wild type EGFR who had previously received one or two chemotherapy regimens were enrolled in this trial. Erlotinib was initially administered at a dose of 150 mg/day orally until disease progression or unacceptable toxicities occurred. The primary endpoint was the objective response rate. RESULTS: Forty patients were enrolled between May 2009 and January 2014. An objective response was observed in 8 patients (20%, 95%CI=9.1-35.7%), and the disease control rate reached 62.5% (95%CI=45.8-77.3%). After a median follow-up period of 12.2 months (range=1.4 47.2 months), the median progression-free survival period was 5.0 months (95%CI=2.3-7.6 months), and the median survival period was 12.2 months (95%CI=6.1 24.7 months). Major toxicities were skin disorders, fatigue, and anorexia. Most adverse events were grade 2 or less, but 13 patients (32.5%) required a dose reduction. Two patients developed interstitial lung disease, that was nevertheless reversible, and there were no treatment-related deaths. CONCLUSION: Although the percentage of patients requiring dose reduction seemed relatively higher than that in previous studies, erlotinib is a potentially useful therapeutic option for unselected elderly patients with previously treated advanced or recurrent NSCLC, as has been also shown for younger patients. PMID- 27272801 TI - Acute Renal Failure Associated with Lenalidomide Treatment in Multiple Myeloma: A Rare Occurrence? AB - Renal failure is a frequent complication of multiple myeloma (MM). Recently, the combination of lenalidomide-dexamethasone has become one of the cornerstone regimens for the treatment of MM. Impairment of renal function exacerbation is a rare, but potential, complication of lenalidomide therapy in plasma cell dyscrasias. We present two patients who developed exacerbation of renal function during their first cycle of therapy with lenalidomide. In the first case, we present a 76-year-old-male with MM and impaired renal function, who declined two weeks after initiation of second-line therapy with lenalidomide. His renal functions improved after discontinuation of lenalidomide and with supportive care. In the second case, we describe a 61-year-old woman who was started on lenalidomide for relapsed MM and admitted to intensive care unit three weeks later due to severe renal failure. Despite intensive supportive care, her renal function deteriorated even more and she died. We conclude that renal failure is an uncommon, but serious, potential complication of lenalidomide therapy in plasma cell dyscrasias, particularly MM. Close monitoring of renal function is clearly recommended during this treatment. PMID- 27272802 TI - Balancing Prolonged Survival with QoL Using Low-dose Pazopanib Maintenance: A Comparison with the PALETTE Study. AB - BACKGROUND: A consensus has not been reached regarding the optimal pazopanib dosing schedule, which we determined in patients who received pazopanib at our Institution. PATIENTS AND METHODS: Twenty-five patients who were prescribed pazopanib between 2012 and 2015 were included in this retrospective analysis. RESULTS: The median progression-free survival (PFS) time was 7.7 months. This time (various doses) was similar to that achieved by high-dose pazopanib in the PALETTE study. The log-rank test revealed no significant differences in the PFS times between the low- and high-dose pazopanib groups, with the majority of patients receiving a dose of 400 mg, indicating that controlling the side-effects might be more critical than administering higher doses. CONCLUSION: Pazopanib should be started from a low dose with careful increase to avoid pazopanib related side-effects, which is necessary to provide a balance between the life prolonging effects of pazopanib and quality of life (QoL) of patients. PMID- 27272803 TI - Total Thyroidectomy Versus Lobectomy for the Treatment of Follicular Thyroid Microcarcinoma. AB - AIM: To compare the effectiveness of total thyroidectomy versus thyroid lobectomy for the treatment of follicular thyroid microcarcinoma. PATIENTS AND METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results 18 Database. The study cohort included patients diagnosed with follicular thyroid microcarcinoma between 1988 and 2009, treated with either total thyroidectomy or thyroid lobectomy. Propensity-score analysis using inverse probability weighting was used to control for allocation bias. RESULTS: A total of 203 patients were identified. The 5-year overall survival was 98% for patients treated with lobectomy and 99% for those treated with total thyroidectomy; this difference was not statistically significant (p=0.13). Unadjusted analysis and propensity-score analysis revealed no difference in overall survival between the two treatment groups (p=0.15 and p=0.49, respectively). CONCLUSION: Total thyroidectomy does not appear to offer any survival advantage over thyroid lobectomy for patients with follicular thyroid microcarcinoma. PMID- 27272804 TI - Survival Outcomes in Early Stage Laryngeal Cancer. AB - AIM: To evaluate survival outcomes of radiotherapy versus surgical resection in the treatment of early stage laryngeal cancer. PATIENTS AND METHODS: Data was extracted from the Surveillance, Epidemiology, and End Results 18 Database. The cohort included 5,301 patients diagnosed with stages I and II laryngeal squamous cell carcinoma between 1992 and 2009, treated with either surgical therapy or radiotherapy. RESULTS: Patients who received surgical therapy had better overall survival (OS) than patients who received radiation therapy (p<0.001). The difference in OS between treatment groups remained after stratification by stage (p<0.001 for Stage I; p=0.03 for Stage II) and subsite (p<0.001). On multivariable analysis, the radiotherapy group had worse OS (hazard ratio (HR)=1.29). CONCLUSION: Patients with early-stage laryngeal cancer treated with surgical therapy have better survival outcomes than patients treated with non surgical therapy. PMID- 27272805 TI - Systemic Inflammatory Response After Open, Laparoscopic and Robotic Surgery in Endometrial Cancer Patients. AB - AIM: To study inflammatory response and nutritional biomarkers in operated endometrial cancer (EC) patients. MATERIALS AND METHODS: A total 109 consecutive EC patients undergoing open laparotomy (LT), laparoscopic (LS) or robot-assisted surgery (RS) were studied. Twenty four patients served as controls. Pre- and postoperative levels of inflammatory and nutritional biomarkers were analyzed prospectively. RESULTS: The estimated blood loss was significantly lower in RS compared to all other groups. C-reactive protein (CRP) and interleukin-6 (IL-6) correlated with each other and exhibited positive correlation with age, body-mass index (BMI), leukocyte count, platelet count, kynurenine, kynurenine/tryptophan ratio and urinary neopterin and a negative correlation with vitamin D and retinol. Hemoglobin, retinol, alpha-tocopherol, vitamin D and citrulline concentrations decreased and inflammatory biomarkers increased after surgery to a different extent in LT, LS, RS and control groups. CONCLUSION: The present data demonstrate a differential response to surgical trauma in patients with endometrial carcinoma. PMID- 27272806 TI - Incidentally Detected Focal Liver Lesions - A Common Clinical Management Dilemma Revisited. AB - BACKGROUND: Detection of asymptomatic focal liver lesions (FLL) is increasing because of a widespread use of modern radiologic imaging. Most of these lesions are benign, though malignancy often has to be ruled out, which is posing a diagnostic challenge. AIM: To critically evaluate our treatment strategy in the context of recently published American College of Gastroenterology (ACG) guidelines. PATIENTS AND METHODS: The medical records of patients who underwent surgery for asymptomatic, incidentally detected FLL from 2005-2012 were reviewed. Primary end-points were the congruence of suspected diagnosis and final pathology, as well as the identification of predictors of malignancy. A systematic review was undertaken to help define a standardized management. RESULTS: Eighty patients, 37 male and 43 female with a mean age of 57 years (range=16-83) were included, harboring 39 (49%) malignant and 41 (51%) benign, asymptomatic hepatic lesions. Hepatocellular carcinoma (HCC) (n=24) represented most of malignant FLL, followed by cholangiocellular carcinoma (CCC) (n=10), whereas focal nodular hyperplasia (FNH) (n=19) and liver hemangioma (n=7) were the predominant benign entities. Fifty-one patients (64%) had a correct preoperative diagnosis, while patients with FNH were most commonly misdiagnosed (53%). We identified age (p<0.001) and male sex (p=0.013) as risk factors for malignancy in an asymptomatic FLL. CONCLUSION: Despite recent technical advances of the modern radiology setting a correct preoperative diagnosis in an asymptomatic FLL remains challenging. Male gender and old age seem to correlate with malignancy. In the absence of biomarkers and evidence-based guidelines, a multidisciplinary approach in an experienced tertiary referral center is recommended for an optimized individual management. PMID- 27272807 TI - High Pre-treatment Plasma D-Dimer Level as a Potential Prognostic Biomarker for Cervical Carcinoma. AB - BACKGROUND/AIM: We aimed to evaluate the prognostic significance of high pre treatment plasma D-dimer levels in patients with cervical carcinoma (CC) after adjusting for venous thromboembolism. PATIENTS AND METHODS: Relationships between the clinicopathological characteristics and the overall (OS) and progression-free (PFS) survival rates of patients with CC (N=129) were examined. Survival was calculated using the Kaplan-Meier method and prognostic indicators assessed using a Cox proportional hazards model. RESULTS: A high pre-treatment plasma level of D dimers, detected in 42.6% of cases (N=55), was associated with advanced tumour stage. In the multivariate analysis, high pre-treatment plasma D-dimer levels, tumour stage, histological type, and carcinoembryonic antigen (CEA) levels were identified as independent prognostic factors for OS, while tumour stage and CEA levels were identified as independent prognostic factors for PFS. CONCLUSION: A high pre-treatment plasma level of D-dimers represents an independent prognostic biomarker for CC that could assist in identifying high-risk populations for treatment decisions. PMID- 27272808 TI - Vascular Endothelial Growth Factor in Plasma and Pleural Effusion Is a Biomarker for Outcome After Bevacizumab plus Carboplatin-Paclitaxel Treatment for Non-small Cell Lung Cancer with Malignant Pleural Effusion. AB - AIM: Malignant effusion is associated with high serum and plasma levels of vascular endothelial growth factor (VEGF). There are no biomarkers of outcome for bevacizumab treatment in patients with malignant pleural effusion (MPE). We previously reported that carboplatin-paclitaxel plus bevacizumab was effective for patients with advanced non-squamous non-small cell lung cancer (NSCLC) and MPE, although we did not evaluate the relationship between treatment outcomes and plasma or pleural effusion levels of VEGF. Therefore, this study evaluated whether plasma or pleural effusion VEGF might predict bevacizumab treatment outcome. PATIENTS AND METHODS: We enrolled 23 patients with NSCLC and MPE between September 2010 and June 2012. Plasma VEGF levels were measured in 19 patients and pleural VEGF levels were measured in 22 patients. RESULTS: Compared to patients with a low plasma VEGF level, patients with a high level exhibited significantly shorter overall survival (OS: 13.8 vs. 6.5 months, p=0.04), progression-free survival (PFS: 8.7 vs. 4.8 months, p<0.01), and period to re-accumulation of MPE (pPFS: 9.7 vs. 6.2 months, p=0.02). Compared to patients with a low VEGF level in pleural effusion, patients with a high VEGF level exhibited significantly shorter OS (19.6 vs. 6.9 months, p<0.01) and pPFS (9.6 vs. 6.7 months, p=0.04), although there was no significant difference in their PFS (6.6 vs. 5.9 months, p=0.18). CONCLUSION: VEGF levels in the plasma and pleural effusion may predict the outcome of bevacizumab treatment in patients with NSCLC and MPE. PMID- 27272809 TI - SOX2 and ALDH1 as Predictors of Operable Breast Cancer. AB - AIM: Sex-determining region Y-box binding protein-2 (SOX2) and aldehyde dehydrogenase-1 (ALDH1) are known cancer stem-cell markers, and represent candidate predictors for breast cancer prognosis. In this study we investigated the relationships between SOX2/ALDH1 expression and prognosis. MATERIALS AND METHODS: One hunred and two breast cancer surgical specimens were immunohistochemically analyzed for SOX2 and ALDH1 expression. RESULTS: Disease free survival (DFS) and overall survival (OS) were significantly poorer for SOX2 positive patients than SOX2-negative (p=0.0024 and p=0.0021, respectively), and for ALDH1-positive patients than ALDH1-negative (p=0.0049 and p=0.0083). DFS and OS were worse for SOX2- or ALDH1-positive patients than double-negative (p=0.0053 and p=0.0166). While an obvious tendency toward worse DFS was seen for estrogen receptor (ER)-negative patients, and attenuated for ER-positive, only SOX2/ALDH1 any-positive patients showed significantly poorer DFS (p=0.0258). CONCLUSION: SOX2 and ALDH1 can be considered markers of poor prognosis, particularly in ER negative patients. SOX2/ALDH1 any-positivity might also offer a reliable predictor of poor prognosis. PMID- 27272810 TI - Initial Results of Hypofractionated Carbon Ion Radiotherapy for Cholangiocarcinoma. AB - AIM: To report initial results of hypofractionated carbon ion radiotherapy (C-ion RT) for cholangiocarcinoma. PATIENTS AND METHODS: Data regarding seven patients with cholangiocarcinoma treated by C-ion RT were analyzed. Prescribed doses were 52.8 Gy [relative biological effectiveness (RBE)] or 60.0 Gy (RBE) in four fractions for intrahepatic cases and 12 fractions for hilar hepatic/close to gastro-intestinal tract cases. Local control and overall survival were evaluated and toxicity was graded using Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up period was 16 months. There were two patients with stage I cancer, one with stage II, one with stage III, and three with stage IVA. Local control was achieved in five out of seven patients (71%) and survival was maintained in six out of seven patients (86%). There were no occurrences of acute or late toxicity of grade 3 or higher. CONCLUSION: Initial results show that hypofractionated C-ion RT appears to be tolerated and effective for cholangiocarcinoma. PMID- 27272811 TI - Semiautomatic Whole-lesion Apparent Diffusion Coefficient Assessment for Early Prediction of Liver Tumor Response to Radioembolization. AB - AIM: To evaluate volume-based apparent diffusion coefficient (ADCVOL) values for early prediction of therapy response after radioembolization (RE) of primary and secondary liver malignancies using a semiautomatic, image analysis software prototype. PATIENTS AND METHODS: In a retrospective analysis, 74 target lesions were assessed in terms of therapy response 1 month after RE using magnetic resonance imaging. Changes of the diameter of the target lesions, the mean ADC value in a representative single-slice region of interest (ADCROI) and mean ADCVOL were correlated. RESULTS: The median progression-free interval (PFI) of patients overall was 3.5+/-5.9 months. PFI in patients with an ADCVOL increase was statistically significantly longer than in patients with an ADCVOL decrease (mean PFI=6.5 vs. 2.5 months; p=0.0374). No correlation between PFI and early changes in lesion diameter or ADCROI was found. CONCLUSION: Semiautomatic, software-based ADC volume measurements seem to offer a clinically valuable parameter for early prediction of therapy response in patients after RE. PMID- 27272813 TI - Analysis of Circulating Tumor Cells in Prostate Cancer Patients at PSA Recurrence and Review of the Literature. AB - BACKGROUND: Circulating tumor cells have been described in prostate cancer patients at diagnosis and in the metastatic phase but little is known on their role at biochemical PSA recurrence. PATIENTS AND METHODS: Patients radically cured with either prostatectomy or radiotherapy were sequentially included at PSA recurrence. The presence of CTCs was evaluated by the CellSearch system. RESULTS: Twenty-nine patients were accrued at PSA recurrence. Median PSA at recurrence was 7.2 ng/ml (range=3.86-51.0 ng/ml). The median time to PSA progression was 4.66 years (range=0.1-16 years). CTCs were detected in one patient (3%) with low numbers (1 CTC/7.5 ml). CONCLUSION: In patients radically cured for prostate cancer at biochemical recurrence, CTCs are detected at very low levels in a minority of patients. Further studies are required to investigate alternative methods of CTC detection and the possible role of the bone marrow pre-metastatic niche at biochemical recurrence. PMID- 27272812 TI - Late Rectal Toxicity from Image-guided Intensity Modulated Radiotherapy for Prostate Cancer. AB - AIM: Late rectal toxicity (LRT) was retrospectively evaluated in men with prostate cancer treated with image-guided intensity modulated radiotherapy (IG IMRT). PATIENTS AND METHODS: Between May 2008 and December 2009, 47 men with prostate adenocarcinoma were treated with IG-IMRT using in-room computed tomography (CT). RESULTS: The median time to grade 2 LRT was 12 months (range=1 24 months). Two of 3 men who developed grade 2 LRT had received treatment for diabetes, and the other was receiving anticoagulant/antiplatelet therapy (AC therapy). Their rectal wall V70 (the volume of rectal wall receiving 70 Gy) values were 12.6%, 13.0%, and 13.3%. Univariate analysis revealed that V70 of the rectal wall was the only significant risk factor for LRT (p=0.0073). CONCLUSION: No man with V70 <=12.0% experienced grade 2 LRT. Strict rectal wall V70 <=12% dose constraints should be considered when treating prostate cancer patients who are also receiving diabetic or AC therapy. PMID- 27272815 TI - A Total Radiation Dose of 70 Gy Is Required After Macroscopically Incomplete Resection of Squamous Cell Carcinoma of the Head and Neck. AB - AIM: To contribute to the definition of the optimal total radiation dose and to determine the role of concurrent chemotherapy after macroscopically incomplete resection of squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Twenty-six patients treated with postoperative radio(chemo)therapy following macroscopically incomplete resection were evaluated. Total radiation dose (70 Gy vs. 59.4-66 Gy), concurrent chemotherapy (yes vs. no) plus six factors were investigated for locoregional control (LRC) and overall survival (OS). RESULTS: On analyses of LRC, 70 Gy was significantly superior to 59.4-66.0 Gy. Two-year LCR rates were 94% and 25%, respectively (p<0.001). Concurrent chemotherapy significantly improved 2-year LRC (90% vs. 0%, p<0.001). Both 70 Gy (92% vs. 11%, p<0.001) and concurrent chemotherapy (80% vs.0%, p<0.001) also resulted in better OS. CONCLUSION: A total radiation dose of 70 Gy was significantly superior to lower doses regarding both LCR and OS. Concurrent chemotherapy is also very important to achieve optimal outcomes. PMID- 27272814 TI - ABCG2 Overexpression Confers Poor Outcomes in Hepatocellular Carcinoma of Elderly Patients. AB - Backgroung/Aim: Breast cancer resistance protein [BCRP/ATP-binding cassette subfamily G member 2 (ABCG2)] is a member of the ATP-binding cassette transporter family, used as a maker of cancer stem cells (CSCs) and thought to be responsible for drug resistance by pumping them out of cells. However, its precise role in various cancer types has been controversial, and the aim of this study was to investigate the expression of ABCG2 in hepacellular carcinoma (HCC) and relate the results to established prognostic factors. PATIENTS AND METHODS: We conducted analysis of 181 HCC and paired-match adjacent normal liver tissue by immunohistochemistry from tissue array of slides. RESULTS: The mean score for ABCG2 expression was higher in tumor than in adjacent normal liver tissue of HCC patients (p<0.001). There was a statistically significant correlation between ABCG2 expression and age, differentiation status and hepatitis B surface antigen (p=0.031, p=0.015 and p=0.033, respectively). Additionally, increased expression of ABCG2 in HCC and its statistically significant correlation with hepatitis B surface antigen was found in elderly (p=0.039), not in younger patients (p=0.518). Importantly, by using Kaplan-Meier and Cox regression analysis, overall survival in patients with high expression of ABCG2 was found reduced in elderly patients (p=0.029 and p=0.081, respectively). CONCLUSION: ABCG2 can be used as a target for the development of novel therapies in HCC. PMID- 27272816 TI - The Value of Lymph Node Dissection in the Surgery of Colorectal Cancer Liver Metastases. AB - BACKGROUND/AIM: Liver resection is the best treatment for metastatic colorectal cancer (CRC). Hepatic lymph node metastases are considered as extrahepatic disease and represent an unfavorable prognostic factor. However, extrahepatic disease, when resectable, provides no contraindication for surgical therapy. The aim of this study was to evaluate the prevalence of hepatic lymph node involvement in our patients' cohort. PATIENTS AND METHODS: Twenty patients submitted to resection for colorectal liver metastases were studied prospectively. Three areas for lymph node dissection were defined and analyzed separately. Lymph nodes were examined by hematoxylin and eosin staining and immunohistochemistry for Pan-Keratin. RESULTS: In average, 5 lymph nodes were harvested per patient. Macroscopic enlargement was not a definite sign for metastatic involvement. No morbidity or mortality was associated with lymphadenectomy. In our patients' collective, no cases of lymph node metastases occurred. CONCLUSION: There is no evidence of a survival benefit after lymph node dissection in patients with CRC liver metastases in the literature. Systematic lymphadenectomy can, however, provide a prognostic tool to better plan further treatment. PMID- 27272817 TI - Efficacy of Ethinylestradiol Re-challenge for Metastatic Castration-resistant Prostate Cancer. AB - BACKGROUND: There has recently been renewed interest in the use of estrogens as a treatment strategy for castration-resistant prostate cancer (CRPC). The purpose of this study was to evaluate the feasibility and efficacy of ethinylestradiol re challenge (re-EE) in the management of CRPC. PATIENTS AND METHODS: Patients with metastatic CRPC who received re-EE after disease progression on prior EE and other therapy were retrospectively reviewed for prostate-specific antigen (PSA) response, PSA progression-free survival (P-PFS) and adverse events. RESULTS: Thirty-six re-EE treatments were performed for 20 patients. PSA response to the initial EE treatment was observed in 14 (70%) patients. PSA response to re-EE was 33.3% in 36 re-EE treatments. The median P-PFS for patients treated with initial and re-EE was 7 months and 4 months, respectively. Interestingly, PSA response to re-EE was observed even in non-responders to initial EE, and those treated with multiple re-EE. No patients developed cardiovascular or thromboembolic events. CONCLUSION: Re-EE may be safely repeated several times and can lead to a prolonged disease control in selected patients. Re-challenge with EE appears to be a reasonable option worth considering for patients with metastatic CRPC. PMID- 27272818 TI - Does the Rectus Sheath Block Analgesia Reduce the Inflammatory Response Biomarkers' IL-1ra, IL-6, IL-8, IL-10 and IL-1beta Concentrations Following Surgery? A Randomized Clinical Trial of Patients with Cancer and Benign Disease. AB - AIM: To evaluate whether the post-surgery placement of the rectus sheath block analgesia (RSB) reduces the inflammatory response following surgery. The main hypothesis of our study was to find any correlation between patients' pain experience, numeric rating scale (NRS) postoperatively and concentrations of inflammatory response biomarkers, such as interleukin-1 receptor antagonist (IL 1ra), IL-6, IL-8, IL-10, IL-1beta, in patients with benign disease and cancer. PATIENTS AND METHODS: Initially, 46 patients with midline laparotomy were randomized to the placebo group (n=11) and to one of the three active groups; single-dose (n=12), repeated-dose (n=12) and continuous infusion (n=11) RSB analgesia groups. Plasma concentrations of high-sensitivity C-reactive protein (hs-CRP) and five interleukins (IL-1ra, IL-6, IL-8, IL-10, IL-1beta) were measured at three time points; just before, immediately after and 24 h after operation. The primary end-point was to compare plasma concentrations of the hs CRP and five interleukins in the placebo group and in the three different RSB analgesia groups in patients with benign disease and cancer. RESULTS: The placebo group and three active groups were similar in terms of demographic variables and perioperative data. Of the anti-inflammatory cytokines, patients in the continuous infusion group had significantly higher IL-10 median values postoperatively than the three other study groups (p=0.029). In addition, patients in the three active groups combined had significantly higher IL-10 median values immediately after operation than the placebo group (p=0.028; in all patients with benign disease and cancer). There is a significant correlation between the individual values of NRS and IL-10 values postoperatively in the placebo group and the three active groups separately (r=0.40, p=0.03) and also a significant correlation between the individual values of the NRS scale and IL 1beta values postoperatively in the placebo group and the three active groups separately (r=0.38, p=0.04). CONCLUSION: Placement of RSB analgesia does not significantly reduce the inflammatory response biomarkers' concentrations in patients with benign disease or cancer patients. A new finding in the present work is a significant correlation in the NRS scale versus plasma concentrations of anti-inflammatory cytokine IL-10 and pro-inflammatory cytokine IL-1beta postoperatively suggesting that inflammation and pain are related. PMID- 27272819 TI - The Role of Image-guided Radiotherapy in the Treatment of Anorectal Cancer Using Prone Belly-board Positioning. AB - AIM: To evaluate Radiation Therapy Oncology Group planning target volume margins of 7-10 mm for radiation therapy in anorectal cancer using prone belly-board positioning without image guidance. PATIENTS AND METHODS: 375 kV cone beam computed tomography image-guided radiotherapy (IGRT) images from 20 patients treated for anorectal cancer were retrospectively analyzed for setup shifts. We calculated the total translational shift for each patient and the frequency with which setup shifts exceeded 7 mm and 10 mm. RESULTS: A total of 42.7% of treatments required shifts >7 mm and 20.8% >10 mm. The mean translational shift was 7.1 mm. 70% of patients experienced shifts >=7 mm in 20% or more of their treatments and 25% of >=10 mm in 20% or more of their treatments; 15% experienced shifts >=10 mm in over half of their treatments. van Herk calculations suggest margins of 12.8 mm are necessary for accuracy without IGRT. CONCLUSION: IGRT using a prone belly board and 7-10 mm margins requires daily image-guidance to prevent planning target volume misses and ensure optimal dose delivery. PMID- 27272820 TI - Clinicopathological Features of Cases with Primary Breast Cancer not Identified by 18F-FDG-PET. AB - Several studies have reported that high F18-fluorodeoxyglucose (FDG) uptake is predictive of poor prognosis and aggressive features in patients with breast cancer. While these studies evaluated the prognostic value for cases with high FDG uptake, they did not elucidate the meaning of FDG negativity in primary breast cancer. In this study, we evaluated the clinicopathological features of breast cancer cases without FDG uptake. We retrospectively investigated the cases of 219 consecutive patients with primary breast cancer who underwent FDG-positron emission tomography (PET) preoperatively. Among the 219 patients, 25 (11.4%) did not have FDG uptake in the tumor. The 219 cases with breast cancer were divided into two groups based on the presence of FDG uptake in the primary tumor. The present univariate analysis revealed that histology, small invasive tumor size, high estrogen receptor (ER) or progesterone receptor (PgR) expression, low nuclear grade and absence of lymph node metastasis were significantly associated with negative FDG uptake in the primary tumor. On the other hand, the size of ductal spread was not significantly different between the two groups. Multivariate analysis revealed that small-size tumor invasion and lower nuclear grade were statistically significant. Among the 25 cases without FDG uptake, there was no recurrent disease in spite of there being no case that underwent chemotherapy, while 4 cases among the 194 cases with FDG uptake had disease recurrence. Our findings imply that preoperative FDG negativity in primary breast cancer is effective in predicting better prognosis, but is less effective in predicting ductal spread. Cases without FDG uptake in the primary tumor may have a lower risk of recurrent disease and may be able to safely avoid adjuvant chemotherapy. PMID- 27272821 TI - Hepatic Resection for Liver Metastases from Cervical Cancer Is Safe and May Have Survival Benefit. AB - The goal of this study was to evaluate the single-centre experience with hepatectomy for liver metastases from cervical cancer (CCLM). Fifteen patients who underwent such surgery at the Fundeni Clinical Hospital between January 2002 and April 2014 were retrospectively reviewed. Liver lesions diagnosed at more than 6 months from cervical cancer diagnosis were classified as metachronous lesions, while lesions occurring within the first 6 months were considered synchronous lesions. Two patients were diagnosed with synchronous CCLM, while the other 13 patients had metachronous. Early postoperative death occurred in a single patient with metachronous liver metastases and pelvic recurrence, but this was not related to liver surgery. The median overall survival for the entire cohort was 18 months from the time of liver resection; patients with metachronous lesions had an improved outcome when compared to those with synchronous lesions. In patients with metachronous liver metastases, prognostic factors associated with an improved outcome were the general biological status of the patient, grade of tumoural differentiation and absence of other abdomino-pelvic recurrences. In multivariate analysis, only the grade of differentiation was statistically significant. In conclusion, hepatic resection for liver metastases from cervical cancer can be performed safely, may prove effective, and should be part of the multimodal treatment. PMID- 27272822 TI - Effect of Sarcopenic Obesity on Outcomes of Living-Donor Liver Transplantation for Hepatocellular Carcinoma. AB - BACKGROUND/AIM: We aimed to evaluate the effect of body composition on the outcome of living-donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We performed LDLT in 153 patients with HCC and divided the patients into two groups based on skeletal muscle mass-to-visceral fat area ratio (SVR), as assessed by computed tomography (CT) measurement, namely a low-SVR group (n=38) and a not-low SVR group (n=112). We compared surgical outcomes between the two groups. RESULTS: A low SVR was significantly correlated with a higher body mass index and male sex. No differences were found between the two groups in terms of other factors. The patients in the low-SVR group had a significantly poorer prognosis than those in the not-low SVR group in terms of recurrence-free (p=0.01) and overall (p=0.03) survival. The results of the multivariate analysis showed low SVR to be an independent and prognostic indicator for patients with HCC who had undergone LDLT. CONCLUSION: Pre-transplant body composition measured by CT is a major determinant of prognosis in LDLT for HCC in Japan. PMID- 27272823 TI - Once Daily Accelerated Partial Breast Irradiation: Preliminary Results with Helical Tomotherapy(r). AB - BACKGROUND: Accelerated partial breast irradiation (APBI) is becoming an option for patients with low-risk breast cancer. The current practice is 38.5 Gy in 10 fractions b.i.d. over 5 days. This fractionation has a higher bioequivalent dose compared to the standard schedule. We report on preliminary results of once-daily APBI in patients treated with TomoTherapy(r). PATIENTS AND METHODS: Patients with unifocal-breast disease who underwent breast-conserving surgery were enrolled in the study. Treatment was administered with TomoTherapy, by contouring in accordance with the NSABP B-39/RTOG 0413 APBI protocol. Treatment schedule was 38.5 Gy in 10 once-daily fractions. EORTC Cosmetic Rating System was adopted for cosmetic outcome. RESULTS: From 2010 to 2013, 111 patients were treated. With a median follow-up of 34 months, no ipsilateral breast recurrence was observed. Very few patients (1-4%) assessed their cosmetic outcome as fair or poor during follow-up. CONCLUSION: Once-daily APBI with TomoTherapy yielded good cosmetic results without compromising local control efficacy. PMID- 27272824 TI - Clinical Impact of Laparoscopy and Endoscopy Cooperative Surgery (LECS) on Gastric Submucosal Tumor After its Standardization. AB - BACKGROUND/AIM: Laparoscopy and endoscopy cooperative surgery (LECS) is an excellent surgical procedure that utilizes the advantages of both methods. This study was designed in our hospital to evaluate the clinical usefulness of LECS for the removal of gastric submucosal tumors after its standardization. PATIENTS AND METHODS: Between 2007 and 2015, 62 consecutive patients underwent surgical resection for gastric submucosal tumors. LECS has been standardized since 2010. RESULTS: (i) There were no significant differences in background factors between patients (such as sex, age, body mass index (BMI), tumor size and postoperative complications), before or after the standardization of LECS. However, after the standardization of LECS, patients had a lower incidence of gastrectomy and wedge resection (WR) (p<0.001), a smaller amount of blood loss (p=0.001) and a shorter hospital stay after surgery (p<0.001) than those before standardization. (ii) LECS was associated with a significantly shorter maximum surgical margin of resected tumors (p=0.020, LECS vs. WR=10.0 vs. 15.0 mm) compared to WR. Patients with upper-third tumors were more frequently treated by LECS than by WR (p=0.014; LECS vs. WR=76 % vs. 27 %). CONCLUSION: Standardization of LECS contributes to reduction of unnecessary gastrectomy for gastric submucosal tumors. In particular, LECS may have merit in the removal of upper-third tumors by avoiding wedge resection, which carries the risk of excessive resection and deformity of the stomach. PMID- 27272825 TI - Ten-year Survivors After Contemporary Management of Advanced 'Horseshoe' Anterior Commissure Laryngeal Cancer. AB - BACKGROUND: Combinations of treatment modalities for locally extensive carcinomas of the larynx constitute the standard of care. Advanced 'horseshoe' anterior commissure laryngeal cancer (HACLC) is a disease entity that has not received much attention in the literature. The aims of this study were to evaluate prolonged survival in patients after standard combined therapy for HACLC and to identify clinicopathological factors influential towards an extended outcome. PATIENTS AND METHODS: Fourteen patients (10-year survivors) with stage III or IV laryngeal cancer involving the anterior commissure and both true vocal cords were treated with total laryngectomy (and postoperative radiotherapy in 11 individuals). RESULTS: During follow-up, ranging from 123 to 256 months, locoregional recurrent disease and distant metastasis were not observed. Complications after therapy were manageable and few. The long-term survivors were particularly difficult to characterize. CONCLUSION: The optimal treatment for advanced HACLC has not been clarified; however, in this study, total laryngectomy and the indicated use of postoperative radiotherapy, were successful in achieving long-term disease-free survival. Predictive factors for longevity were not detected in this limited experience. PMID- 27272826 TI - The Contribution of Dental Implants to Functional Artificial Restoration After Treatment of Oral Cancer. AB - BACKGROUND/AIM: The aim of this study was to evaluate dental implants with regard to artificial restoration of oral function and quality of life in patients with oral cancer. PATIENTS AND METHODS: We examined 134 implants in 41 patients who had undergone jawbone resection as treatment for oral cancer. The patients were aged 44-89 (mean=61.5) years, and the male to female ratio was 27:14. RESULTS: The 5-year implant success rate was 91.0%. Of the 12 unsuccessful implants, four were embedded on bone grafts with skin flaps, four were embedded on skin flaps using muscle, and four were embedded after peripheral resection. Of the 41 patients, 11 received radiation, but exposure to radiation was not associated with implant loss. The level of satisfaction on the visual analog scale before development of oral cancer was set at 100 mm. Satisfaction fell to 47.0 mm after primary treatment, but recovered to 82.6 mm after implant therapy. CONCLUSION: Patient satisfaction after implant therapy was high, and the implants resulted in improved quality of life. A high proportion of cases involving use of skin flaps resulted in implant loss. Constructing an immobile mucous membrane by replacement of a skin flap with a skin graft may facilitate self-maintenance of implants. PMID- 27272827 TI - Prognostic Impact of EGFR Driver Mutations on Postoperative Disease Recurrence in Lung Adenocarcinoma. AB - AIM: The purpose of this study was to investigate the prognostic significance of epidermal growth factor receptor (EGFR) sensitizing mutations in patients with lung adenocarcinoma who underwent complete surgical resection. PATIENTS AND METHODS: We retrospectively reviewed the clinical records of 164 patients with lung adenocarcinoma who underwent surgery from 2003 to 2010. Seventy-four patients harbored EGFR mutations; two with exon 18 mutations, 27 with exon 19 mutations, and 45 with exon 21 mutations. RESULTS: There were more female patients and more never-/light smokers among patients with EGFR mutations than among patients without EGFR mutations. Patients with EGFR mutations had a trend for better disease-free survival and overall survival compared to patients without EGFR mutations (p=0.068 and p=0.049, respectively). Patients with exon 21 mutations had significantly better disease-free survival than patients with exon 19 mutations (p=0.027). CONCLUSION: Adenocarcinomas harboring EGFR exon 21 mutation were less malignant than adenocarcinomas harboring exon 19 mutation. PMID- 27272828 TI - Distance from Primary Tumor Is the Strongest Predictor for Early Onset of Brain Metastases in Melanoma. AB - BACKGROUND/AIM: The frequency of brain metastasis (BM) is up to 45-50% in patients with advanced melanoma. Our aim was to identify the risk factors for the early occurrence of BM. PATIENTS AND METHODS: A total of 333 patients with BM were identified from our database of 2,972 patients with melanoma between 2003 2015. RESULTS: The median elapsed time to BM (TTBM) was significantly associated with Breslow thickness, ulceration, location, and patient age. Head and neck location was the strongest predictor for early BM development [hazard ratio (HR)=1.81, 95% confidence interval (CI)=1.05-3.12; p=0.031) followed by Breslow thickness >2 mm (HR=1.53, 95% CI=1.04-2.23; p=0.027). Body part-specific median TTBM was 51.5, 43, 38.5, 32, 35, 36.5, 35.5 and 19 months in leg-foot, thigh, abdomen-pelvic, chest-back, lower arm-hand, upper arm-shoulder, face-neck and scalp regions, respectively. CONCLUSION: We suggest brain magnetic resonance imaging follow-up in the high-risk patient group of patients with melanoma in the head and neck region, especially for those with primary melanoma over Breslow 2 mm located in the scalp. PMID- 27272829 TI - Potential Impact of the Overall Treatment Time on Outcomes after Whole-brain Irradiation with 10*3 Gy for Brain Metastases. AB - AIM: To investigate the impact of the overall treatment time (OTT) of whole-brain irradiation (WBI) with 10*3 Gy on outcomes in patients with brain metastases. PATIENTS AND METHODS: Seventy-three patients who started WBI on Monday (OTT=12 days, including one weekend without irradiation) were compared to 257 patients who began WBI on Tuesday to Friday (OTT=14 days, including two weekends) for intracerebral control and survival. Seven additional factors were analyzed, including age, gender, Karnofsky performance score (KPS), tumor type, number (N) of brain lesions, extracerebral metastases and interval between cancer diagnosis and WBI. RESULTS: On univariate analysis, age (p=0.039), KPS (p<0.001) and N brain metastases (p=0.006) were associated with intracerebral control; OTT had no significant impact (p=0.20). Age (p<0.001), KPS (p<0.001), N brain metastases (p=0.037) and extracerebral metastases (p<0.001) were associated with survival; OTT had no significant impact (p=0.37). CONCLUSION: OTT (12 vs. 14 days) had no significant impact on outcomes after WBI with 10*3 Gy. PMID- 27272830 TI - Depth of Hepatic Infiltration and Lymph Node Swelling as Factors for Considering Surgery for T2-4 Gallbladder Carcinoma Patients. AB - BACKGROUND/AIM: The aim of the present study was to clarify if the degree of hepatic infiltration and lymph node swelling of gallbladder carcinoma (GBC) should be held as deciding factors for T2-4 GBC patients to undergo surgery. PATIENTS AND METHODS: Fifty consecutive patients with T2-4 GBC who underwent surgery were reviewed retrospectively. We investigated the preoperative information and imaging factors as predictors of survival. RESULTS: The estimated overall survival in all patients was lower in patients with hepatic infiltration >=5 mm (n=12) than in those with <5 mm (n=38) (p=0.003). Multivariate analyses demonstrated that liver infiltration >=5 mm (OR=2.251; 95%CI=0.906-5.596, p=0.081) and lymph node swelling (OR=2.462; 95%CI=1.034-5.859, p=0.042) were risk factors of poor survival. CONCLUSION: Our results suggested that >=5 mm liver infiltration and lymph node swelling may serve as deciding factors for surgery consideration in GBC patients. PMID- 27272831 TI - Radiation Therapy Alone Provides Excellent Outcomes for Spinal Cord Compression from Vertebral Lymphoma. AB - AIM: Malignant spinal cord compression (SCC) is treated with radiotherapy (RT). Additional neurosurgery has become more widely used since a trial showed a benefit for selected patients. Although lymphomas were excluded from that trial, neurosurgery is also increasingly being performed in these patients. This study investigated whether neurosurgery is actually required for this group. PATIENTS AND METHODS: Twenty-nine patients receiving RT alone for SCC from vertebral lymphoma were analyzed for motor function, walking ability, in-field recurrence and survival. RESULTS: Overall response was 100% (72% improvement, 28% stable). At 1, 6 and 12 months after RT, 83%, 100% and 100% of patients were able to walk; 64%, 100%, and 100% of non-ambulatory patients regained their walking ability. Freedom from in-field recurrence was 100% at 6 and 12 months. Survival rates at 6 and 12 months were 79% and 75%. CONCLUSION: RT alone resulted in excellent outcomes for SCC from lymphoma. These patients may not require surgery. PMID- 27272832 TI - Magnetic Tissue Engineering for Voice Rehabilitation - First Steps in a Promising Field. AB - BACKGROUND/AIM: The voice is one of the most important instruments of communication between humans. It is the product of intact and well-working vocal folds. A defect of these structures causes dysphonia, associated with a clear reduction of quality of life. Tissue engineering of the vocal folds utilizing magnetic cell levitation after nanoparticle loading might be a technique to overcome this challenging problem. MATERIALS AND METHODS: Vocal fold fibroblasts (VFFs) were isolated from rabbit larynges and cultured. For magnetization, cells were incubated with superparamagnetic iron oxide nanoparticles (SPION) and the loading efficiency was determined by Prussian blue staining. Biocompatibility was analyzed in flow cytometry by staining with annexin V-fluorescein isothiocyanate propidium iodide, 1,1',3,3,3',3'-hexamethylindodicarbo-cyanine iodide [DiIC1(5)] and propidium idodide-Triton X-100 to monitor phosphatidylserine exposure, plasma membrane integrity, mitochondrial membrane potential and DNA degradation. RESULTS: Isolated VFFs can be successfully loaded with SPION, and optimal iron loading associated with minimized cytotoxicity represents a balancing act in magnetic tissue engineering. CONCLUSION: Our data are a firm basis for the next steps of investigations. Magnetic tissue engineering using magnetic nanoparticle loaded cells which form three-dimensional structures in a magnetic field will be a promising approach in the future. PMID- 27272834 TI - Expression of the Insulin-like Growth Factor-1 Receptor in Odontogenic Myxoma. AB - Odontogenic myxoma (OM) is a rare mesenchymal tumour arising in the jaws. The origin and pathogenesis of OM is poorly understood. The aim of this study was to characterize OM by immunolocalization of certain antigens in the tumour that are relevant for cellular differentiation, migration and maintenance. MATERIALS AND METHODS: Five OMs were immunohistochemically investigated for expression of nestin, CD133, podoplanin, and insulin-like growth factor 1 receptor (IGF-1R). RESULTS: OM failed to react with antibodies applied in this study, with the exception of IGF-1R in tumour cells. DISCUSSION: OM is a poorly characterized benign, invasive tumour of the jaws. The absence of stem cell marker in OM does not exclude possible temporary expression of these antigens during certain phases of tumour development. The identification of IGF-1R in OM is shared with numerous tumours and indicates the ability of these tumour cells to respond to growth factors. PMID- 27272833 TI - Toxicity of Mitoxantrone-loaded Superparamagnetic Iron Oxide Nanoparticles in a HT-29 Tumour Spheroid Model. AB - BACKGROUND/AIM: Cancer research is commonly carried out in two-dimensional (2D) cell cultures, which poorly reflect in vivo settings where the growing tumours are exposed to mechanical forces and biochemical gradients. In this study we established a HF-29 colon carcinoma tumor spheroid model to investigate the effect of free mitoxantrone (MTO) and its nanoparticle-bound form (SPION(MTO)) under 3D cell culture conditions. MATERIALS AND METHODS: Tumour spheroids were generated by seeding HT-29 colon carcinoma cells on agarose-coated cell culture wells. Growth of the spheroids was monitored daily by transmission microscopy upon treatment with free MTO, SPION(MTO) or unloaded SPION. RESULTS AND CONCLUSION: Unloaded SPION did not affect the spheroid size compared to untreated controls, while both free MTO and SPION(MTO) inhibited growth of the spheroids in a dose- and time-dependent manner. In comparison to free MTO, the effect of SPION(MTO) on spheroid growth was slightly delayed. Further analyses are necessary to investigate if MTO infiltrates spheroids in its nanoparticle-bound form or whether it is released from SPION before infiltration. PMID- 27272835 TI - Cherubism: A Case Report with Surgical Intervention. AB - Cherubism is a rare benign, autosomal-dominant hereditary fibro-osseous condition predominantly affecting the jaws. Symmetrical cyst-like expansions of the jaws cause the characteristic facial swellings. The disease is often associated with severe malposition of teeth. The gene for cherubism is src homology 3 binding protein 2 (SH3BP2) located on chromosome 4p16.3. The repeated experience of this self-limiting disorder in affected individuals published in the medical literature has resulted in a wait-and-see strategy regarding therapeutic options. Indeed, cessation and regression of even large bone expansions can be expected in early adulthood. Nevertheless, severe facial disfiguring and functional impairment can make surgical intervention necessary. This report details the surgical procedures carried out in a patient with progressive and disfiguring jaw expansions at the end of adolescence, the mutation of SH3BP2 gene, and the limited effect of surgically assisted orthodontic tooth movement in a patient with disease-associated impaired tooth development and tooth eruption. PMID- 27272836 TI - Expression of DOG1 (Using SP31) in Poorly Differentiated Carcinoma of the Head and Neck. AB - BACKGROUND: The calcium-activated chloride channel protein discovered on gastrointestinal stromal tumour 1 (DOG1) is expressed in a variety of normal and neoplastic tissues. DOG1 is a specific marker for gastrointestinal stromal tumour. In the head and neck region, DOG1 is a sensitive discriminator for acinar cell carcinoma. Only a few publications have presented data concerning the expression of DOG1 in head and neck squamous cell carcinoma (HNSCC). The expression of DOG1 in HNSCC appears to be associated with a poor prognosis. The aim of this study was to analyze the expression pattern of DOG1 in poorly differentiated carcinoma of the upper aerodigestive tract. MATERIALS AND METHODS: A total of 84 specimens from 31 patients with carcinomas of the upper aerodigestive tract were immunohistochemically investigated for DOG1 expression. Inclusion criterion was poorly to undifferentiated carcinoma of the head and neck, but samples of the same resection site that exhibited moderate or well differentiated squamous cell carcinoma were also enrolled. Immunoreactivity in carcinomas was estimated using a visual score (0: negative; 1: basally positive, 2: parabasally positive, 3: completely positive, 4: basally and parabasally positive). RESULTS: Fifteen out of 84 specimens were immunoreactive to antibody to DOG1 (17.8%). DOG1 immunoreactivity was restricted to eight patients (25.8%). However, DOG1 expression was considerably heterogeneous in tumours, with three (9.6%) cases showing a positive reaction in all samples. Basal and parabasal staining patterns (five specimens each) dominated. DISCUSSION: This study demonstrated expression of DOG1 to be restricted to some poorly differentiated carcinomas of the upper aerodigestive tract. Although the proportion of DOG1 positive carcinomas was moderate compared to results of previous studies on head and neck cancer tissues, DOG1 expression possibly indicates a subset of HNSCC. Further studies are necessary to investigate the heterogeneity and clinical relevance of DOG1 expression in HNSCC. PMID- 27272837 TI - Determination of Interleukin-4, -5, -6, -8 and -13 in Serum of Patients with Breast Cancer Before Treatment and its Correlation to Circulating Tumor Cells. AB - BACKGROUND/AIM: Circulating tumor cells (CTCs) in women with breast cancer are an indication of prognosis before starting systemic treatment. The aim of this study was the evaluation of cytokine profiles as marker for CTC involvement. MATERIALS AND METHODS: The analysis of CTCs, the time of blood sampling and the methodology were prospectively designed. There were two groups of patients: 100 women with a positive result for presence of CTCs and 100 women negative for CTCs. These groups were matched into pairs by tumor factors and survival/death. A multi-array ELISA was used to screen T-helper cell (Th) 2 cytokines. The results were analyzed by Spearman correlation coefficient and Mann-Whitney U-test. RESULTS: In patients who were CTC-negative, expression of interleukin-8 (IL-8) and IL-13 was increased (p=0.017 and p=0.045, respectively) if they were negative for progesterone receptor. In patients who died from their tumor, correlation between hormone receptor negativity and an increase in IL-4 was found. IL-5 was increased in patients with lymph node-positive and human epidermal growth factor receptor 2 (HER2)-positive disease (p=0.042). Moreover IL-4 was increased in patients with progesterone receptor-positive and estrogen receptor-negative status (p=0.024). Furthermore, the level of IL-6 was increased in patients with tumor grade G3 without progesterone receptor expression. CONCLUSION: Th2 cytokines are significantly modified in patients who are CTC-negative and progesterone receptor positive. We suppose that an increase of IL-4 depends on hormone receptor status. In literature, a correlation between IL-4 and resistance to apoptosis is described. We suspect that IL-4 is responsible for the poor outcome of these cases. PMID- 27272838 TI - Immunohistochemical Evaluation of the Role of p53 Mutation in Cervical Cancer: Ser-20 p53-Mutant Correlates with Better Prognosis. AB - BACKGROUND: Cervical cancer is driven by human papillomavirus virus-specific oncoprotein E6. E6 interacts with E3 ubiquitin-protein ligase, resulting in the proteolysis of p53 protein. The aim of this study was to analyze one TP53 mutation in patients with cervical cancer and to correlate it to prognosis. MATERIALS AND METHODS: A total of 248 paraffin-embedded tumor samples were stained for mutated p53 protein. The distribution and intensity of staining both in the nucleus and cytoplasm were evaluated with a semi-quantitative immunohistochemical score. RESULTS: A total of 66% of studied cervical carcinomas expressed the mutated p53 protein. The overall survival was better for patients expressing the mutated p53 protein in the nucleus. CONCLUSION: Interestingly, we found a very high mutation rate of TP53 in a cancer type where p53 is initially inactivated via E6 during the development of cervical cancer. An unexpected finding is the correlation of this mutation with better survival, possibly due to better response to therapy. PMID- 27272839 TI - FOXP3+ Cells Recruited by CCL22 into Breast Cancer Correlates with Less Tumor Nodal Infiltration. AB - BACKGROUND: Regulatory T-cells (Tregs) are a T-cell subpopulation with suppressive capacities, which are specifically attracted by C-C motif chemokine 22 (CCL22). Treg infiltration of tumors is associated with a poor prognosis in many patients. We aimed to investigate whether CCL22 is expressed in human breast cancer and whether its presence is associated with Treg infiltration. MATERIALS AND METHODS: Eighty paraffin-embedded human breast cancer samples were stained for CCL22 and for the Treg-specific transcription factor forkhead box P3 (FOXP3). Expression was evaluated in a semi-quantitative manner. RESULTS: FOXP3(+) cells infiltrated 50% of the breast tumors. Moreover, Treg infiltrated 93% of the tertiary lymphoid structures. CCL22 expression positively correlated with FOXP3(+) cell infiltration into the tertiary lymphoid structures. CONCLUSION: Our results demonstrate that CCL22 expression correlates with infiltration by FOXP3(+) cells. Interestingly, Treg presence negatively correlated with positive nodal status. In addition to their unfavorable role as mediators of evasion from antitumor immune response, Tregs might also have a beneficial role by reducing inflammation thereby limiting early tumor growth and spreading. PMID- 27272840 TI - Effect of BSA-coated Superparamagnetic Iron Oxide Nanoparticles on Granulosa Cells. AB - BACKGROUND: Since superparamagnetic iron oxide nanoparticles (SPION) possess unique features, they provide a huge platform for medical applications, especially for cancer diagnosis and therapy (e.g. imaging, and drug targeting). However, heterogeneous effects on mammalian cells with regard to reproductive tissue are described. An experimental study was carried out to study the effects of SPIONs on both the expression of steroid hormone receptor and viability of granulosa cells, which play a key role in ovarian health and fertility. MATERIALS AND METHODS: Human granulosa cells were cultured in vitro and incubated with different concentrations of SPIONs. After 48 h, steroid receptor expression and cell viability were evaluated. RESULTS: Treatment of granulosa cells with SPIONs did not affect estrogen receptor beta1 or progesterone receptor-A expression and had no significant effect on cell viability. CONCLUSION: Nanoparticles precoated with bovine serum albumin (BSA) do not alter granulosa cell phenotype, whereas literature suggests that other nanoparticles induce apoptosis and reduce steroid receptor expression. Our data indicate an overall better outcome using SPIONs coated with BSA. PMID- 27272841 TI - Recurrent Maxillary Odontogenic Myxoma Following Partial Maxillary Resection and Consecutive Osseous Reconstruction Including Tooth Transplantation. AB - Odontogenic myxoma (OM) is a rare tumour arising in the jaws. The tumour is purported to be odontogenic in origin due to the frequent localisation of the tumour inside the jaws in close relation to teeth. The aim of this report was to detail the course of a patient who developed OM of the maxilla, underwent adequate ablative surgery and reconstruction, including tooth transplantation to the original tumour site, and subsequently developed a local recurrence in close proximity to the teeth transplanted to the reconstructed maxilla 6 years after the first diagnosis. Once again, a partial maxillary resection was performed, with no reconstruction. The patient has been free from tumour recurrence for over 20 years. We discuss the current hypothesis on OM pathogenesis and the possible impact of actively dividing cells on tumour re-growth. PMID- 27272842 TI - Expansive Extracranial Growth of Intracranial Meningioma in Neurofibromatosis Type 2. AB - The purpose of this report is to detail three rare cases of neurofibromatosis type 2 (NF2) with symptomatic extracranial extension of intracranial meningioma. We present ocular findings, imaging techniques applied, pathological findings of the space-occupying lesions, and therapy. One of these patients, the daughter of one of the other individuals, presented with a large neck mass, but no surgically treatable findings associated with the external growth of the meningioma. The patients complained of symptoms associated with the extracranial portion of the intracranial meningioma, rather than of the intracranial primaries. However, facial and neck surgical care is very limited in patients with such advanced stage tumours. The prolongation of life was unquestionably predominantly determined by the behaviour of the intracranial tumour. Head and neck surgeons should be aware of the rare possibility that solid tumours of this region could be extracranial-extending meningioma in an inherited disease. PMID- 27272843 TI - Mucoepidermoid Carcinoma - Unknown Primary Affecting the Neck. AB - The present report describes therapy and follow-up of a patient who experienced a localized swelling of the neck that proved to be a mucoepidermoid carcinoma. Extensive staging revealed no primary site. Therapy was modified neck dissection followed by external application of chemotherapy combined with fractionated radiotherapy. Over a period of 43 months, the patient has remained free of local tumour growth and distant metastasis. Whereas prognosis of mucoepidermoid carcinoma in general is good, prognosis of patients affected by mucoepidermoid carcinoma with carcinoma of unknown primary is ambiguous. PMID- 27272844 TI - Clinical Value of Squamous Cell Carcinoma Antigen (SCCAg) in Anal Cancer - A Single-Center Retrospective Analysis. AB - AIM: To assess the clinical value of squamous cell carcinoma antigen (SCCAg) in anal cancer for chemoradiotherapy (CRT) patients. PATIENTS AND METHODS: In 24 patients with SCC of the anus, SCCAg was determined before CRT and at every follow-up visit. RESULTS: 16/24 (66.7%) had normal SCCAg and 11/16 (68.8%) achieved complete remission (CR), while 7/8 (87.5%) with elevated SCCAg achieved CR. In two patients, elevated SCCAg was observed after radiotherapy. One was false-positive and one was true-positive leading to diagnosis of metachronous recurrent and metastatic disease after interim CR. CONCLUSION: SCCAg was inappropriate to predict the clinical outcome but can provide additional information on the regular follow-up examinations to detect a relapse. PMID- 27272845 TI - Expression of the Tumor-associated Mucin 1 Epitope Analyzed with the Humanized PankoMab-GEXTM Antibody in Malignant and Normal Tissues of the Head and Neck. AB - BACKGROUND: During neoplasia, glycosylation changes. In this setting, mucins, especially mucin 1 (MUC1), become carriers for oncofetal carbohydrates and relieve invasive growth. The recently described tumor-associated MUC1 epitope TA MUC1 is primarily restricted to malignancies and is overexpressed in these tissues. The humanized monoclonal antibody PankoMab-GEX specifically recognizes TA-MUC1. MATERIALS AND METHODS: Laryngeal cancer specimens (n=125) and normal tissue of head and neck (n=7) were used in this study. Paraffin-embedded sections were incubated with PankoMab-GEX. Staining reaction was carried out using peroxidase (POD) labeling and diaminobenzidine (DAB). Breast cancer tissue was used as positive control and negative control used non-specific mouse IgM. Semi quantitative evaluation by two independent double-blinded investigators, including a pathologist, used the immunoreactive score (IRS) of Remmele and Stegner. RESULTS: A total of 31 out of 125 laryngeal cancer specimens were classified as G1. Of these, 22 (71%) were completely negative for TA-MUC1, the remaining 9 showed very weak staining, with an IRS of 2. A total of 94 cases of cancer specimens were classified as G2 and G3; 34 of them were also negative, but 60 had an IRS of up to 9. All investigated normal tissue of the upper aerodigestive tract was completely negative for TA-MUC1. CONCLUSION: G1 tumors are completely negative or do not reach an IRS relevant range. The finding that G1 tumors are completely negative for TA-MUC1 or have IRS<=2 can be helpful for histopathological examination, especially concerning tumor grading. Therefore, this antibody holds great potential for use as a therapeutic antibody in laryngeal cancer. PMID- 27272846 TI - Thyroid Hormones and Vitamin D in Patients with Breast Cancer with Mutations in BRCA1 or BRCA2 Genes. AB - AIM: The thyroid hormones free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and vitamin D seem to be involved in the process of differentiation and proliferation of breast tissue. Little is known about these factors in breast cancer 1 and 2 (BRCA1/BRCA2)-mutation carriers with breast cancer (BC). The purpose of this investigation was to evaluate the association of thyroid gland function and vitamin D with BC in patients with BRCA mutations. PATIENTS AND METHODS: At the Department of Hereditary Breast and Ovarian Cancer of the Ludwig Maximilian University Hospital of Munich, 40 patients with BC (10 patients with mutations in the BRCA1 gene, 10 with mutations in the BRCA2 gene, and 20 without mutations, as control group) were selected for analysis of the following parameters: fT3, fT4, TSH and vitamin D. The primary diagnosis was made between 21 and 62 years of age. The patients were matched by age. Anamnestic data were evaluated concerning disorders of the thyroid gland and primary BC diagnosis. RESULTS: In patients with BC, BRCA mutations are not associated with thyroidal dysfunctions. A significantly increased level of vitamin D in BRCA2-mutation carriers compared to those without mutation (p=0.02) was detected. The grade of the tumors in the BRCA2 group was better than in those with mutation. BRCA1-mutation carriers had an increased incidence of primary BC diagnosis during pregnancy (30% vs. 0%) in comparison to those without mutation. CONCLUSION: No association between the thyroid hormones and BC in BRCA1/2 mutation carriers was found. Vitamin D was significantly elevated in BRCA2 mutation carriers and the observation of a better tumor grade in this group could be consistent with the ability of vitamin D to inhibit growth and induce differentiation. PMID- 27272847 TI - Sport in the Rehabilitation of Patients After Total Laryngectomy. AB - AIM: Laryngectomy due to cancer leads to decreased physical activity of patients. Rehabilitation programs focus on the improvement of voice and swallowing but the role of rehabilitation sports for such patients is unknown. PATIENTS AND METHODS: We interviewed all 38 patients (five women, 33 men; median age 56 years) of our patient's advocacy group. All had undergone laryngectomy because of cancer. We asked them to report their sporting activities and summarized their descriptions. RESULTS: Overall, 12 patients were members of our swimming group and had performed aqua gymnastics and swimming training in order to stabilize or improve the muscle structures of the neck and backbone. A further four patients only took part in swimming training. The training frequency was twice per month; when patients were introduced to the program, they increased this frequency to 4 5/month. Three patients started cycling with mountain bikes covering distances of between 30 and 50 km. A further two patients were able to follow our cycling program using e-bikes. Twenty patients reported walking weekly between 10 and 16 km. All patients summarized the positive impact of sports on their personal well being. CONCLUSION: Swimming, aqua-fitness, cycling and (Nordic) walking are favourable sport disciplines for patients after laryngectomy for laryngeal cancer. Special training programs should be developed and included in rehabilitation procedures for patients after multimodal therapy of laryngeal cancer. PMID- 27272848 TI - Immunohistochemical Evaluation of E6/E7 HPV Oncoproteins Staining in Cervical Cancer. AB - BACKGROUND/AIM: High-risk human papillomavirus (HPV) subtypes (i.e. 16 and 18) lead to uterine cervical cancer as well as HPV-positive oropharyngeal cancer (OSCC), a form of head and neck cancer. The induction of HPV-induced cancer is driven by virus-specific oncoproteins E6 and E7. E6 protein of HPV types 16 and 18 interacts with the E3 ubiquitin protein ligase, resulting in ubiquitination and proteolysis of tumor protein p53. E7 inactivates retinoblastoma protein (Rb) by phosphorylation followed by an increase of free eukaryotic transcription factor E2F (E2F) in the cell. This leads to an increase of cyclin-dependent kinase inhibitor p16, that is used as an immunohistochemical marker of HPV associated OSCC. Unfortunately, p16 is not exclusively increased by E7 oncoprotein in carcinogenesis. Therefore, the aim of this study was to develop an immunohistochemical approach for the direct detection of E6/E7 oncoproteins in uterine cervical cancer as well as in OSCC. MATERIAL AND METHODS: Paraffin sections of uterine cervical cancer and 130 were analyzed. Immunohistochemical staining protocols were evaluated with tissue slides from patients with cervical dysplasia (CIN III) and squamous epithelial carcinoma tissue with HPV infection. Liver and placental tissues were used as negative controls. E6-Specific antibody (Biorbyt) was used as primary antibody. The polymer staining method and diaminobenzidine were applied for further development. Panels of E7-specific antibodies were tested. Again, the polymer staining method and diaminobenzidine were applied for further development. RESULTS: E6-Specific antibody revealed specific and intense staining after pre-incubation of tissue slides with citrate buffer solution. Only the E7 antibody obtained from Chemicon showed intense and specific staining in patients with CIN III and squamous epithelial carcinoma tissue. Pre-incubation with proteinase K diminished non-specific reaction. CONCLUSION: Our results revealed a useful staining protocol for the immunohistochemical evaluation of E6/E7 oncoprotein expression in uterine cervical cancer, as well as in HPV-positive oropharyngeal cancer. Advantages of this method compared to mRNA in situ hybridization of E6/E7 are the much lower costs, as well as the broader applicability in pathological practice. PMID- 27272849 TI - Methylation of the ER-alpha Promoter Is Influenced by its Ligand Estrogen in Osteosarcoma Cells SAOS-2 In Vitro. AB - BACKGROUND/AIM: The aggressive fast-growing osteosarcoma is the most common primary malignant bone tumor. The relevance of estrogen as a key player in bone metabolism and bone tumor is well-known. At the molecular level, estrogen activates the estrogen receptor alpha (ERalpha) as a natural ligand of this receptor. ERalpha acts as a transcription factor by binding to the "estrogen response element" (ERE) and regulates the expression of a various number of genes. Epigenetic processes, e.g. the methylation of the "cytosine-phosphatidyl guanine (CpG) islands" can change the transcription of target genes and subsequently the protein expression. As DNA methylation is generally associated with gene transcription repression, up until now little is known about the ERalpha methylation in osteosarcoma cells. The aim of the present pilot study was to evaluate the methylation status of ERalpha in osteosarcoma cells SAOS-2 and MG 63 after stimulation with estrogen. MATERIALS AND METHODS: SAOS-2 and MG 63 cells were cultured in DMEM. After treatment with 10 nmol estrogen (E2) for 24 h, the expression of ERalpha was detected by immunocytochemistry (ICC). As controls we used untreated cells. Staining was evaluated semi-quantitatively by the immunoreactive score of Remmele and Stegner (IRS). To determine mRNA gene expression, extracted RNA was transcribed into c-DNA and a quantitative real-time PCR (qRT-PCR) was carried out. The semi quantitative evaluation of the ERalpha mRNA was based on the 2(-DeltaDeltact) method using untreated cells as reference control. One microgram of each extracted genomic DNA sample was converted with bisulfite and a real-time methylation-specific PCR (rt-MSP) was performed. RESULTS: The estrogen-stimulated SAOS-2 cells showed a significant increase of ERalpha expression. A 7-fold up-regulation of ERalpha mRNA confirmed the results of immunocytochemistry. Methylation of the ERalpha promoter was not detected in treated cells. In contrast, we identified methylation of the ERalpha promoters in untreated cells. The staining of MG 63 cells showed a weak gain of ERalpha expression in the stimulated cells, as well as a weak increase of the ER-alpha mRNA (2-fold). Methylation of the ERalpha promoters was not detectable in either treated or untreated cells. CONCLUSION: The methylation status of ERalpha in osteosarcoma cells is affected by estrogen. These findings indicate that epigenetic changes of genomic DNA regulate ERalpha synthesis. Taken together, our results suggest that SAOS-2 cells can be an interesting model for further investigating ERalpha synthesis. In addition, the evaluation of ERalpha methylation in osteosarcoma specimens is in progress. PMID- 27272850 TI - Endometrial Adenocarcinoma: Analysis of Circulating Tumour Cells by RT-qPCR. AB - BACKGROUND: Endometrial adenocarcinoma is a frequently occurring cancer in women, accounting for 42,000 deaths every year. Despite treatment with standard therapy, occurrence of remote metastases and local recurrences is high. Through help of RT qPCR minimal residual disease could be detected and characterized, facilitating therapeutic decision making. MATERIALS AND METHODS: A number of marker genes were first tested in model systems and genes that performed best, were consequently used for the examination of 13 blood samples from endometrial carcinoma patients. RESULTS: Cytokeratin 19 and MIG7 were chosen for the analysis in patient samples. Both genes were found up-regulated in small tumours and in one large tumour, but no statistical correlations could be revealed between expression levels of these two genes and tumour characteristics. CONCLUSION: There seems to be a coherence between gene expression and the stage of tumorigenesis, but the number of samples is still too small, to be able to obtain statistical significant differences. PMID- 27272851 TI - New Marker Genes for Real-Time PCR-based Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients. AB - BACKGROUND: The detection of circulating tumour cells (CTCs) from peripheral blood of cancer patients can be carried out by real-time PCR approaches using different gene expression levels of tumour cells and surrounding blood cells. MATERIALS AND METHODS: Potential marker genes were first analyzed in a model system and then applied to 20 blood samples of adjuvant breast cancer patients and gene expression levels were correlated to tumour characteristics. RESULTS: The mean of gene expression levels was found elevated for the four genes analyzed in the adjuvant breast cancer patient group in comparison to the samples of the group of healthy donors, but no correlation between gene expression and tumour characteristics could be detected as being statistically significant. CONCLUSION: The results demonstrated, that the employed methodology is functional, but has to be refined by certain approaches like simultaneously running a state-of-the-art system of CTC-detection comparing the results, and by an enlargement of patient collective and number of marker genes. PMID- 27272852 TI - Immunocytochemical Characterization of Disseminated Tumour Cells from Bone Marrow of Breast Cancer Patients. AB - BACKGROUND: The occurrence of disseminated tumour cells in bone marrow of patients with breast cancer is linked to a worse prognosis. We present a method for DTC detection from bone marrow samples based on immunocytochemistry, using breast cancer-associated glycosylation molecules as markers for detection and characterization. MATERIALS AND METHODS: A double immunofluorescence staining of a pan-cytokeratin (CK) marker and either Tn or O-Acetyl-GD3 was carried out in artificial and patient bone marrow samples. RESULTS: The sample in which most cells stained positive for CK/Tn and CK/O-AC-GD3, was obtained from a patient who certainly had remote metastases. All other bone marrow samples showed heterogenous staining, so no correlation to tumour characteristics could be revealed. CONCLUSION: A certain characterization of tumour cells can be achieved by a double staining of bone marrow samples with CK and a glycosylation marker. For future studies, analysis should be extended to a larger patient collective and further examination of more glycosylation markers should be carried out. PMID- 27272854 TI - Genome Editing. The Next Step in Gene Therapy. PMID- 27272855 TI - RNA-Protein Complexes and Interactions. Methods and Protocols. PMID- 27272856 TI - Natural Killer Cells. PMID- 27272857 TI - Epigenetics - A Different Way of Looking at Genetics. PMID- 27272858 TI - Immunology of the Skin. Basic and Clinical Sciences in Skin Immune Responses. PMID- 27272860 TI - Statistical Genomics. Methods and Protocols. PMID- 27272859 TI - Novel Biomarkers in the Continuum of Breast Cancer. PMID- 27272862 TI - Targeting Oral Cancer. PMID- 27272861 TI - Introduction to Molecular Vaccinology. PMID- 27272863 TI - Utility of Bromelain and N-Acetylcysteine in Treatment of Peritoneal Dissemination of Gastrointestinal Mucin-Producing Malignancies. PMID- 27272864 TI - Vascular Tumors and Developmental Malformations. Pathogenic Mechanisms and Molecular Diagnosis. PMID- 27272865 TI - Laparoscopic Surgery for Colorectal Cancer. PMID- 27272866 TI - Intestinal Polyposis Syndromes. PMID- 27272867 TI - Prostatitis and Its Management. PMID- 27272868 TI - Immunopharmacogenomics. PMID- 27272870 TI - Immunohistochemistry. Essential Elements and Beyond. PMID- 27272869 TI - Angiogenesis in Health, Diseases and Malignancy. PMID- 27272871 TI - Myeloid-Derived Suppressor Cells and Cancer. PMID- 27272872 TI - Analysis of Single-Cell Data. ODE Constrained Mixture Modeling and Approximate Bayesian Computation. PMID- 27272874 TI - Biphasic Effect of Diabetes on Neuronal Nitric Oxide Release in Rat Mesenteric Arteries. AB - INTRODUCTION: We analysed possible time-dependent changes in nitrergic perivascular innervation function from diabetic rats and mechanisms implicated. MATERIALS AND METHODS: In endothelium-denuded mesenteric arteries from control and four- (4W) and eight-week (8W) streptozotocin-induced diabetic rats the vasoconstriction to EFS (electrical field stimulation) was analysed before and after preincubation with L-NAME. Neuronal NO release was analysed in the absence and presence of L-arginine, tetrahydrobiopterine (BH4) and L-arginine plus BH4. Superoxide anion (O2-), peroxynitrite (ONOO-) and superoxide dismutase (SOD) activity were measured. Expressions of Cu-Zn SOD, nNOS, p-nNOS Ser1417, p-nNOS Ser847, and Arginase (Arg) I and II were analysed. RESULTS: EFS response was enhanced at 4W, and to a lesser extent at 8W. L-NAME increased EFS response in control rats and at 8W, but not at 4W. NO release was decreased at 4W and restored at 8W. L-arginine or BH4 increased NO release at 4W, but not 8W. SOD activity and O2- generation were increased at both 4W and 8W. ONOO- decreased at 4W while increased at 8W. Cu-Zn SOD, nNOS and p-NOS Ser1417 expressions remained unmodified at 4W and 8W, whereas p-nNOS Ser847 was increased at 4W. ArgI was overexpressed at 4W, remaining unmodified at 8W. ArgII expression was similar in all groups. CONCLUSIONS: Our results show a time-dependent effect of diabetes on neuronal NO release. At 4W, diabetes induced increased O2- generation, nNOS uncoupling and overexpression of ArgI and p-nNOS Ser847, resulting in decreased NO release. At 8W, NO release was restored, involving normalisation of ArgI and p nNOS Ser847 expressions. PMID- 27272884 TI - Acousto-microfluidics for screening of ssDNA aptamer. AB - We demonstrate a new screening method for obtaining a prostate-specific antigen (PSA) binding aptamer based on an acoustofluidic separation (acoustophoreis) technique. Since acoustophoresis provides simultaneous washing and separation in a continuous flow mode, we efficiently obtained a PSA binding aptamer that shows high affinity without any additional washing step, which is necessary in other screening methods. In addition, next-generation sequencing (NGS) was applied to accelerate the identification of the screened ssDNA pool, improving the selecting process of the aptamer candidate based on the frequency ranking of the sequences. After the 8(th) round of the acoustophoretic systematic evolution of ligands by exponential enrichment (SELEX) and following sequence analysis with NGS, 7 PSA binding ssDNA aptamer-candidates were obtained and characterized with surface plasmon resonance (SPR) for affinity and specificity. As a result of the new SELEX method with PSA as the model target protein, the best PSA binding aptamer showed specific binding to PSA with a dissociation constant (Kd) of 0.7 nM. PMID- 27272885 TI - Workshop Proceedings: Streamlined Development of Safety Assessment Programs Supporting Orphan/Rare Diseases-Are We There Yet? AB - A workshop entitled "Streamlined Development of Safety Assessment Programs Supporting Orphan/Rare Diseases-Are We There Yet?" was held at the 36th Annual Meeting of the American College of Toxicology in Summerlin, Nevada. The workshop was sponsored by Shire and Ultragenyx and was designed to present the nonclinical considerations for the development of various products for rare diseases. A panel of experts from industry and government highlighted the nonclinical considerations in developing toxicology programs supporting rare disease therapeutics, challenges in preclinical safety assessment, reviewed the current guidance, and presented the progress that has been made to date. The main learning from the workshop was that nonclinical testing of therapeutics targeting rare disease warrants special considerations, and early collaboration between sponsors and health authorities may help optimize the scope and timing of the supportive studies. Specific examples for nonclinical development programs for enzyme replacement therapy (ERT) were presented. Although the symposium focused on ERTs, the concepts are broadly applicable. PMID- 27272886 TI - Satisfaction with information about ionising radiation: a comparative study in Belgium and France. AB - In recent decades efforts have been made to meet societal expectations concerning public access to information and to enable citizens' informed decision-making related to ionising radiation risks. But are people satisfied with the information provided and which factors influence this? This paper investigates lay persons' satisfaction with the information about ionising radiation provided by different communicators in Belgium and France. In particular, it studies the potential influence of risk perception, confidence in authorities, knowledge and education. The study is based on data originating from large scale public opinion surveys (N = 1002 in Belgium; N = 966 in France). Results show that the two countries differ as regards satisfaction with the information provided by specific communicators. Confidence in authorities was revealed in both countries as more important for satisfaction with information than risk perception. Contrary to expectations, general knowledge about ionising radiation had limited or no explanatory power. An additional study for the Belgian sample showed that both perceived trustworthiness and technical competence influence satisfaction with information, but their relative importance depends on the communicator. PMID- 27272887 TI - The Clinical and Cost Effectiveness of Apremilast for Treating Active Psoriatic Arthritis: A Critique of the Evidence. AB - As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of apremilast was invited to submit evidence for its clinical and cost effectiveness for the treatment of active psoriatic arthritis (PsA) for whom disease-modifying anti rheumatic drugs (DMARDs) have been inadequately effective, not tolerated or contraindicated. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This paper provides a description of the ERG review of the company's submission, the ERG report and submission and summarises the NICE Appraisal Committee's subsequent guidance (December 2015). In the company's initial submission, the base-case analysis resulted in an incremental cost effectiveness ratio (ICER) of L14,683 per quality-adjusted life-year (QALY) gained for the sequence including apremilast (positioned before tumour necrosis factor [TNF]-alpha inhibitors) versus a comparator sequence without apremilast. However, the ERG considered that the base-case sequence proposed by the company represented a limited set of potentially relevant treatment sequences and positions for apremilast. The company's base-case results were therefore not a sufficient basis to inform the most efficient use and position of apremilast. The exploratory ERG analyses indicated that apremilast is more effective (i.e. produces higher health gains) when positioned after TNF-alpha inhibitor therapies. Furthermore, assumptions made regarding a potential beneficial effect of apremilast on long-term Health Assessment Questionnaire (HAQ) progression, which cannot be substantiated, have a very significant impact on results. The NICE Appraisal Committee (AC), when taking into account their preferred assumptions for HAQ progression for patients on treatment with apremilast, placebo response and monitoring costs for apremilast, concluded that the addition of apremilast resulted in cost savings but also a QALY loss. These cost savings were not high enough to compensate for the clinical effectiveness that would be lost. The AC thus decided that apremilast alone or in combination with DMARD therapy is not recommended for treating adults with active PsA that has not responded to prior DMARD therapy, or where such therapy is not tolerated. PMID- 27272888 TI - Minilaparotomy-Assisted Transmesenteric-Transjugular Intrahepatic Portosystemic Shunt: Comparison with Conventional Transjugular Approach. AB - PURPOSE: This study was performed to compare the intrahepatic shunt function outcome and procedural complications of minilaparotomy-assisted transmesenteric (MAT)-transjugular intrahepatic portosystemic shunt (TIPS) placement with the conventional transjugular method. METHODS: This is a retrospective review of all patients who had a MAT or conventional TIPS procedure over a 6-year period at our institute. The primary patency rate, fluoroscopy time, technical success, major procedure-related complications, and mortality data were compared between two treatment groups. RESULTS: We included 49 patients with MAT-TIPS, and 63 with conventional TIPS, with an average follow-up of 21.43 months. The primary patency rates at 6 and 12 months were 82.9 and 66.7 % in the conventional TIPS group, and 81.0 and 76.5 % in the MAT-TIPS group (p = 1.000, and 0.529), respectively. There was no significant difference in technical success rate, post-procedure portosystemic pressure gradient, fluoroscopy time, and peri-procedural mortality rate between treatment groups. Major procedural-related complications were seen more frequently among MAT-TIPS patients (p = 0.012). In the MAT-TIPS group, 5 (10.2 %) patients developed post-procedure minilaparotomy, wound-related complications, and 5 (10.2 %) developed bacterial peritonitis; whereas, none of patients with conventional TIPS had either of these complications (p = 0.014). CONCLUSION: While both MAT-TIPS and conventional TIPS had similar shunt primary patency rate and technical success rate, the MAT approach was associated with a significantly higher rate of minilaparotomy-related wound complications or infectious complications. These complications maybe prevented by a change in post procedure monitoring and therapy. PMID- 27272890 TI - Retention in Care among HIV-Infected Adults in Ethiopia, 2005- 2011: A Mixed Methods Study. AB - BACKGROUND: Poor retention in HIV care challenges the success of antiretroviral therapy (ART). This study assessed how well patients stay in care and explored factors associated with retention in the context of an initial ART rollout in Sub Saharan Africa. METHODS: We conducted a mixed-methods study at a teaching hospital in Addis Ababa, Ethiopia. A cohort of 385 patients was followed for a median of 4.6 years from ART initiation to lost-to-follow-up (LTFU-missing appointments for more than three months after last scheduled visit or administrative censoring). We used Kaplan-Meier plots to describe LTFU over time and Cox-regression models to identify factors associated with being LTFU. We held six focus group discussions, each with 6-11 patients enrolled in care; we analyzed data inductively informed by grounded theory. RESULTS: Patients in the cohort were predominantly female (64%) and the median age was 34 years. Thirty percent were LTFU by study's end; the median time to LTFU was 1,675 days. Higher risk of LTFU was associated with baseline CD4 counts <100 and >200 cells/MUL (HR = 1.62; 95% CI:1.03-2.55; and HR = 2.06; 95% CI:1.15-3.70, respectively), compared with patients with baseline CD4 counts of 100-200 cells/MUL. Bedridden participants at ART initiation (HR = 2.05; 95% CIs [1.11-3.80]) and those with no or only primary education (HR = 1.50; 95% CIs [1.00-2.24]) were more likely to be LTFU. Our qualitative data revealed that fear of stigma, care dissatisfaction, use of holy water, and economic constraints discouraged retention in care. Social support and restored health and functional ability motivated retention. CONCLUSION: Complex socio-cultural, economic, and health-system factors inhibit optimum patient retention. Better tracking, enhanced social support, and regular adherence counseling addressing stigma and alternative healing options are needed. Intervention strategies aimed at changing clinic routines and improving patient-provider communication could address many of the identified barriers. PMID- 27272892 TI - Chronic subdural hematomas in Finnish patients with Huntington's disease. AB - BACKGROUND: Many features of Huntington's disease (HD) make these patients susceptible to subdural hematomas (SDH), but there are no previous reports on the epidemiology of SDH in this population. We investigated the incidence and risk factors of chronic SDH. METHODS: A national cohort of 192 Finnish patients with HD was investigated. Information was gathered from medical records and administrative registries. RESULTS: The incidence rate of SDH was 68.3/100,000 person-years among the 192 patients. Seven patients were identified with a chronic SDH at or after the diagnosis of HD. Their age was 58.5 +/- 15.0 years (mean +/- SD) at the time of diagnosis of HD and 60.9 +/- 14.1 years at the time of diagnosis of SDH. The incidence rate of chronic SDH after the diagnosis of HD was 4.7/1000 person-years and by 8.3 years of follow-up the cumulative risk was 5.4 %. Review of the patient charts revealed only a few of the common risk factors for chronic SDH, but the rate of reoperations was high. CONCLUSIONS: The incidence of chronic SDH was higher in patients with HD than that in the general population. Incidence of chronic SDH began to increase at the time of expected motor onset of HD. Common risk factors of SDH were scarce aside from fall-related head injuries. PMID- 27272891 TI - One-Pot C-H Functionalization of Arenes by Diaryliodonium Salts. AB - A transition-metal-free, mild, and highly regioselective synthesis of nitroarenes from arenes has been developed. The products are obtained in a sequential one-pot reaction by nitration of iodine(III) reagents with two carbon ligands, which are formed in situ from iodine(I). This novel concept has been extended to formation of aryl azides, and constitutes an important step towards catalytic reactions with these hypervalent iodine reagents. An efficient nitration of isolated diaryliodonium salts has also been developed, and the mechanism is proposed to proceed by a [2,2] ligand coupling pathway. PMID- 27272893 TI - Vision after trans-sylvian or temporobasal selective amygdalohippocampectomy: a prospective randomised trial. AB - BACKGROUND: Selective amygdalohippocampectomy (SAH) is an accepted surgical procedure for treatment of pharmacoresistant mesial temporal lobe epilepsy, but it may lead to postoperative visual field deficits (VFDs). Here we present a prospective randomised trial comparing the postoperative VFDs after either a trans-sylvian or temporobasal approach for SAH. METHOD: Forty-eight patients were randomly assigned to trans-sylvian (n = 24) or temporobasal (n = 24) SAH. Postoperative VFD were quantitatively evaluated using automated static and kinetic perimetry. In 24 cases, diffusion tensor imaging-based deterministic fibre-tracking of the optic radiation was performed. The primary endpoint was absence of postoperative VFD. The secondary endpoint was seizure outcome and driving ability. RESULTS: Three patients (13 %) from the trans-sylvian group showed no VFD, compared to 11 patients (46 %) from the temporobasal group without VFD (p = 0.01, RR = 3.7; CI = 1.2-11.5). Fifteen patients from each group (63 %) became completely seizure-free (ILAE1). Among those seizure-free cases, five trans-sylvian (33 %) and ten temporobasal (66 %) patients could apply for a driving licence (NNT = 3) when VFDs were considered. Although the trans-sylvian group experienced more frequent VFDs, the mean functional visual impairment showed a tendency to be less pronounced compared with the temporobasal group. DTI based tracking of the optic radiation revealed that a lower distance of optic radiation to the temporal base correlated with increased rate of VFD in the temporobasal group. CONCLUSIONS: Temporobasal SAH shows significantly fewer VFDs and equal seizure-free rate compared with the trans-sylvian SAH. However, in patients in whom the optic radiation is close to the temporal base, the trans sylvian approach may be a preferred alternative. PMID- 27272894 TI - Association between resource utilization and patient satisfaction at a tertiary care medical center. AB - BACKGROUND: The Centers for Medicare and Medicaid Services has emphasized patient satisfaction as a means by which hospitals should be compared and as a component of financial reimbursement. We sought to identify whether resource utilization is associated with patient satisfaction ratings. DESIGN: This was a retrospective, cohort study over a 27-month period from January 2012 to April 2014 of adult respondents (n = 10,007) to the Hospital Consumer Assessment of Healthcare Providers and Systems survey at a tertiary care medical center. For each returned survey, we developed a resource intensity score related to the corresponding hospitalization. We calculated a raw satisfaction rating (RSR) for each returned survey. Multivariable logistic regression was used to determine the association between resource intensity and top decile RSRs, using those with the lowest resource intensity as the reference group. RESULTS: Adjusting for age, gender, insurance payer, severity of illness, and clinical service, patients in higher resource intensity groups were more likely to assign top decile RSRs than the lowest resource intensity group ("moderate" [adjusted odds ratio {aOR}: 1.42, 95% confidence interval {CI}: 1.11-1.83], "major" [aOR: 1.56, 95% CI: 1.22-2.01], and "extreme" [aOR: 2.29, 95% CI: 1.8-2.92]). CONCLUSIONS: Resource utilization may be positively associated with patient satisfaction. These data suggest that hospitals with higher per-patient expenditures may receive higher ratings, which could result in hospitals with higher per-patient resource utilization appearing more attractive to healthcare consumers. Journal of Hospital Medicine 2016;11:785 791. (c) 2016 Society of Hospital Medicine. PMID- 27272895 TI - Factors associated with postoperative requirement of renal replacement therapy following off-pump coronary bypass surgery. AB - Cardiopulmonary bypass usage provokes a systemic inflammatory response resulting in deterioration of renal function. However, risk factors for requiring renal replacement therapy (RRT) following off-pump coronary artery bypass graft surgery (CABG) have not yet been fully elucidated. We reviewed 718 consecutive patients undergoing elective off-pump CABG at our institution, excluding patients on chronic hemodialysis preoperatively. Sub-analysis of patients with preserved renal function, defined as a creatinine level below a cut-off value of 1.12 mg/dL (obtained by receiver operating characteristic curve), was also performed. Of the 718 patients, 41 (5.7 %) required RRT. There were 556 patients (77.4 %) with preserved renal function preoperatively, and 13 (2.4 %) of these required postoperative RRT. Multivariate analysis revealed that age (years) and preoperative serum creatinine (mg/dL) and brain natriuretic peptide (BNP) levels (pg/dL) were associated with RRT [odds ratios (OR) 1.052, 95 % confidence interval (CI) 9.064 and 1.001, respectively, all p < 0.05] in the total population, whereas low albumin concentration was the only independent predictor for RRT in patients with preserved renal function (OR 0.062, p < 0.0001). When creatinine levels were below 1.5 mg/dL, the predictive power of hypoalbuminemia for RRT requirement overwhelmed that of creatinine or BNP levels. Older age, preoperative elevated creatinine and BNP levels were associated with a requirement for RRT following off-pump CABG. In patients with preserved renal function, hypoalbuminemia was most significantly related to the RRT requirement. PMID- 27272896 TI - Assessing utility of exercise test in determining exercise prescription in adolescent and adult patients with repaired tetralogy of fallot. AB - Parameters from cardiopulmonary exercise test (CPET) are useful prognostic factors for patients with repaired tetralogy of fallot (TOF). Its application in exercise prescription remains unclear. This study sought to define its role. We made current exercise recommendations in repaired TOF patients according to European Society of Cardiology (ESC) guideline, which were based on ventricular function, pressure/volume load, pulmonary artery pressure, hypoxemia and arrhythmic burden both at rest and during exercise. CPET parameters (peak oxygen consumption, oxygen uptake efficiency plateau, and E/CO2 slope), along with cardiothoracic ratio, ventricular arrhythmia, QRS duration and NYHA functional status, were used to calculate "score to exercise". 112 repaired TOF adolescent and adult aged 32.6 +/- 10.8 (14.05- to 56.99-year-old, median 30.1) years received exercise recommendations by ESC guideline, which suggested high, moderate and low intensity sports for 45 (40.2 %), 45 (40.2 %), and 22 (19.6 %) patients, respectively. The optimal cut-off values were 67 and 77 % for peak VO2, 86 and 100 % for OUEP, 22 and 28 for E/CO2 slope to correlate to the exercise intensity recommendation. But, individual CPET parameter had low consistency (41 46 %) in making decisions of exercise intensity compared to ESC recommendations. Using the "score to exercise", the consistency rate could be increased to 74.1 %. With "score to exercise" recommended exercise intensity, follow-up result revealed no adverse event related to sports. Individual CPET parameter did not correlate well to the exercise recommendation from ESC. We proposed a scoring system, "score to exercise", which incorporates three CPET parameters with cardiothoracic ratio, ventricular arrhythmia, QRS duration and NYHA functional status. Score to exercise is easy to be assessed and provides useful information for exercise recommendation in patients with repaired TOF. PMID- 27272897 TI - Early chest computed tomography in adult acute severe community-acquired pneumonia patients treated in the intensive care unit. AB - BACKGROUND: The value of early chest computed tomography (CT) was evaluated among severe community-acquired pneumonia (SCAP) patients. METHODS: The study population consisted of 65 of 457 SCAP patients with concomitant chest CT and radiograph performed within 48 h of ICU admission. Each image pair was re evaluated by two radiologists. The type of pneumonia, the presence of pleural fluid and atelectasis were assessed. Therapeutic and diagnostic procedures induced by CT results were analysed together with clinical, microbiological and outcome data. RESULTS: Alveolar pneumonia was observed in 72.3% of patients by radiograph and in 75.4% of patients by CT. Pleural fluid was detected via chest radiograph and CT in 17 (26.2%) and 41 cases (63.1%), (P < 0.001) and atelectasis in 10 (15.4%) and 22 cases (33.8%), (P = 0.002), respectively. In 34 patients (52.3%), the CT revealed 38 new findings (58.5%) not shown in plain chest radiograph. Out of these 34 patients, therapeutic interventions or procedures were performed in 26 (76.5%). The number of infected lobes correlated negatively with the lowest PaO2 /FiO2 ratio (rho = -0.326, P = 0.008) for chest CT scans. CONCLUSION: Compared with chest radiograph, chest CT generated new findings in nearly 60% of SCAP patients, leading to new procedures or changes in medical treatment in nearly 75% of those patients. Chest CT better describes the pulmonary involvement and severity of oxygenation disorder compared to a plain chest radiograph. PMID- 27272898 TI - Experiences and perspectives of children attending a weight loss camp in China: a qualitative study. AB - BACKGROUND: Modernisation, urbanisation and the globalisation of food markets have exposed Chinese children to an obesogenic environment. With the dramatic increase in the prevalence of overweight and obesity among Chinese children, there are now over 2000 weight loss camps for children. The aim of this study was to investigate how one typical weight loss camp operates and to explore the experiences and perceptions of children attending the camp. METHODS: This study utilised ethnographic techniques and semi-structured interviews with children attending a 28-day summer weight loss camp in Hangzhou, China. All children attending at the time of the study were included. Field notes were taken, and interviews with children were recorded, transcribed and analysed into themes. RESULTS: Nine boys and 10 girls aged 7-18 years with a body mass index ranging from 21 to 37 kg/m(2) were interviewed. The weight loss programme combined dietary restriction (<350 calories/meal) and a daily schedule of 8 h of exercise in outdoor temperatures of around 40 degrees C. Field observation and interviews showed that the regime was distressing for all the children who suffered hunger and exhaustion leading to crying, squabbling, fighting and desperate phone calls to parents. All felt their weight loss could not be sustained. CONCLUSIONS: The extreme conditions and total absence of health and nutrition education at the camp were of great concern. Parents should be aware of the potential dangers and long-term ineffectiveness of such interventions. At the very least, these camps must be subject to regulation. PMID- 27272899 TI - Imaging of lower extremity trauma from Boston Marathon bombing. AB - The goal of this study is to describe the imaging features of lower extremity blast injuries in patients encountered in the radiology departments from the Boston Marathon bombings. A total of 115 patients presented to four acute care hospitals on April 15, 2013, 43 of whom presented with lower extremity injuries and were included in this study. The imaging findings of primary, secondary, tertiary, and quaternary blast injuries were evaluated. Forty-one of 43 patients sustained secondary blast injuries to the lower extremities with 31 patients (70 %) having retained shrapnel, seven patients (16 %) having soft tissue lacerations without retained shrapnel, and ten patients (23 %) having lower extremity amputation (7 % double amputees). Eight of these patients (20 %) had lower extremity fractures, and five patients (12 %) had vascular injuries. Two of the 43 patients (5 %) had only tertiary injuries, and five of 43 patients (12 %) were noted to have lower extremity burns, consistent with quaternary blast injury. No primary blast injury occurred in the lower extremities. A vast majority of lower extremity injuries were from secondary blast injury, most commonly from retained shrapnel in 70 % of patients and 23 % of patients sustaining lower extremity amputation. Retained shrapnel in the lower extremity was most commonly ball bearings and pressure cooker fragments, and most injuries affected the leg, followed by the thigh and foot. PMID- 27272900 TI - Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making. AB - Understanding the medical effect of an ever-growing number of human variants detected is a long term challenge in genetic counseling. Functional assays, based on in vitro or in vivo evaluations of the variant effects, provide essential information, but they require robust statistical validation, as well as adapted outputs, to be implemented in the clinical decision-making process. Here, we assessed 25 pathogenic and 15 neutral missense variants of the BRCA1 breast/ovarian cancer susceptibility gene in four BRCA1 functional assays. Next, we developed a novel approach that refines the variant ranking in these functional assays. Lastly, we developed a computational system that provides a probabilistic classification of variants, adapted to clinical interpretation. Using this system, the best functional assay exhibits a variant classification accuracy estimated at 93%. Additional theoretical simulations highlight the benefit of this ready-to-use system in the classification of variants after functional assessment, which should facilitate the consideration of functional evidences in the decision-making process after genetic testing. Finally, we demonstrate the versatility of the system with the classification of siRNAs tested for human cell growth inhibition in high throughput screening. PMID- 27272901 TI - Three-dimensional polymer coated 45S5-type bioactive glass scaffolds seeded with human mesenchymal stem cells show bone formation in vivo. AB - 45S5-type bioactive glasses are a promising alternative to established substitutes for the treatment of bone defects. Because the three-dimensional (3D) structure of bone substitutes is crucial for bone ingrowth and formation, we evaluated the osteoinductive properties of different polymer coated 3D-45S5 bioactive glass (BG) scaffolds seeded with human mesenchymal stem cells (hMSC) in vivo. BG scaffolds coated with gelatin, cross-linked gelatin, and poly(3 hydroxybutyrate-co-3-hydroxyvalerate) were seeded with hMSC prior to implantation into severe combined immunodeficiency mice. Newly formed bone was evaluated with histomorphometry and micro-computed tomography. Bone formation was detectable in all groups, whereas the gelatin-coated BG scaffolds showed the best results and should be considered in further studies. PMID- 27272902 TI - The cytoprotective capacity of processed human cardiac extracellular matrix. AB - Freshly isolated human cardiac extracellular matrix sheets (cECM) have been shown to support stem cell proliferation and tissue-specific lineage commitment. We now developed a protocol for standardized production of durable, bio-functional hcECM microparticles and corresponding hydrogel, and tested its cytoprotective effects on contractile cells subjected to ischemia-like conditions. Human ventricular myocardium was decellularized by a 3-step protocol, including Tris/EDTA, SDS and serum incubation (cECM). Following snap-freezing and lyophilization, microparticles were created and characterized by laser diffraction, dynamic image analysis (DIA), and mass spectrometry. Moreover, cECM hydrogel was produced by pepsin digestion. Baseline cell-support characteristics were determined using murine HL-1 cardiomyocytes, and the cytoprotective effects of ECM products were tested under hypoxia and glucose/serum deprivation. In cECM, glycoproteins (thrombospondin 1, fibronectin, collagens and nidogen-1) and proteoglycans (dermatopontin, lumican and mimecan) were preserved, but residual intracellular and blood-borne proteins were also detected. The median particle feret diameter was 66 MUm (15-157 MUm) by laser diffraction, and 57 MUm (20-182 MUm) by DIA with crystal violet staining. HL-1 cells displayed enhanced metabolic activity (39 +/- 12 %, P < 0.05) and proliferation (16 +/- 3 %, P < 0.05) when grown on cECM microparticles in normoxia. During simulated ischemia, cECM microparticles exerted distinct cytoprotective effects (MTS conversion, 240 +/- 32 %; BrdU uptake, 45 +/- 14 %; LDH release, -72 +/- 7 %; P < 0.01, each). When cECM microparticles were solubilized to form a hydrogel, the cytoprotective effect was initially abolished. However, modifying the preparation process (pepsin digestion at pH 2 and 25 degrees C, 1 mg/ml final cECM concentration) restored the cytoprotective cECM activity. Extracellular matrix from human myocardium can be processed to yield standardized durable microparticles that exert specific cytoprotective effects on cardiomyocyte-like cells. The use of processed cECM may help to optimize future clinical-grade myocardial tissue engineering approaches. PMID- 27272903 TI - Microsphere-based scaffolds encapsulating tricalcium phosphate and hydroxyapatite for bone regeneration. AB - Bioceramic mixtures of tricalcium phosphate (TCP) and hydroxyapatite (HAp) are widely used for bone regeneration because of their excellent cytocompatibility, osteoconduction, and osteoinduction. Therefore, we hypothesized that incorporation of a mixture of TCP and HAp in microsphere-based scaffolds would enhance osteogenesis of rat bone marrow stromal cells (rBMSCs) compared to a positive control of scaffolds with encapsulated bone-morphogenic protein-2 (BMP 2). Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds encapsulating TCP and HAp mixtures in two different ratios (7:3 and 1:1) were fabricated with the same net ceramic content (30 wt%) to evaluate how incorporation of these ceramic mixtures would affect the osteogenesis in rBMSCs. Encapsulation of TCP/HAp mixtures impacted microsphere morphologies and the compressive moduli of the scaffolds. Additionally, TCP/HAp mixtures enhanced the end-point secretion of extracellular matrix components relevant to bone tissue compared to the "blank" (PLGA-only) microsphere-based scaffolds as evidenced by the biochemical, gene expression, histology, and immunohistochemical characterization. Moreover, the TCP/HAp mixture groups even surpassed the BMP-2 positive control group in some instances in terms of matrix synthesis and gene expression. Lastly, gene expression data suggested that the rBMSCs responded differently to different TCP/HAp ratios presented to them. Altogether, it can be concluded that TCP/HAp mixtures stimulated the differentiation of rBMSCs toward an osteoblastic phenotype, and therefore may be beneficial in gradient microsphere-based scaffolds for osteochondral regeneration. PMID- 27272904 TI - The War on Drugs That Wasn't: Wasted Whiteness, "Dirty Doctors," and Race in Media Coverage of Prescription Opioid Misuse. AB - The past decade in the U.S. has been marked by a media fascination with the white prescription opioid cum heroin user. In this paper, we contrast media coverage of white non-medical opioid users with that of black and brown heroin users to show how divergent representations lead to different public and policy responses. A content analysis of 100 popular press articles from 2001 and 2011 in which half describe heroin users and half describe prescription opioid users revealed a consistent contrast between criminalized urban black and Latino heroin injectors with sympathetic portrayals of suburban white prescription opioid users. Media coverage of the suburban and rural opioid "epidemic" of the 2000s helped draw a symbolic, and then legal, distinction between (urban) heroin addiction and (suburban and rural) prescription opioid addiction that is reminiscent of the legal distinction between crack cocaine and powder cocaine of the 1980s and 1990s. This distinction reinforces the racialized deployment of the War on Drugs and is sustained by the lack of explicit discussion of race in the service of "color blind ideology." We suggest potential correctives to these racially divergent patterns, in the form of socially responsible media practices and of clinical engagement with public policy. PMID- 27272905 TI - Effect of biochar addition on short-term N2O and CO2 emissions during repeated drying and wetting of an anthropogenic alluvial soil. AB - Agricultural soils are an important source of greenhouse gases (GHG). Biochar application to such soils has the potential of mitigating global anthropogenic GHG emissions. Under irrigation, the topsoils in arid regions experience repeated drying and wetting during the crop growing season. Biochar incorporation into these soils would change the soil microbial environment and hence affect GHG emissions. Little information, however, is available regarding the effect of biochar addition on carbon dioxide (CO2) and nitrous oxide (N2O) emissions from agricultural soils undergoing repeated drying and wetting. Here, we report the results of a 49-day aerobic incubation experiment, incorporating biochar into an anthropogenic alluvial soil in an arid region of Xinjiang Province, China, and measuring CO2 and N2O emissions. Under both drying-wetting and constantly moist conditions, biochar amendment significantly increased cumulative CO2 emission. At the same time, there was a significant reduction (up to ~20 %) in cumulative N2O emission, indicating that the addition of biochar to irrigated agricultural soils may effectively slow down global warming in arid regions of China. PMID- 27272906 TI - Histone acetyltransferase HAT4 modulates navigation across G2/M and re-entry into G1 in Leishmania donovani. AB - Histone acetyltransferases impact multiple processes. This study investigates the role of histone acetyltransferase HAT4 in Leishmania donovani. Though HAT4 was dispensable for survival, its elimination decreased cell viability and caused cell cycle defects, with HAT4-nulls experiencing an unusually long G2/M. Survival of HAT4-nulls in macrophages was also substantially compromised. DNA microarray analysis revealed that HAT4 modestly regulated the expression of only a select number of genes, thus not being a major modulator of global gene expression. Significantly, cdc20 was among the downregulated genes. To ascertain if decreased expression of cdc20 was responsible for HAT4-null growth and cell cycle defects we expressed LdCdc20 ectopically in HAT4-nulls. We found this to alleviate the aberrant growth and cell cycle progression patterns displayed by HAT4-nulls, with cells navigating G2/M phase and re-entering G1 phase smoothly. HAT4-nulls expressing LdCdc20 ectopically showed survival rates comparable to wild type within macrophages, suggesting that G2/M defects were responsible for poor survival of HAT4-nulls within host cells also. These are the first data analyzing the in vivo functional role of HAT4 in any trypanosomatid. Our results directly demonstrate for the first time a role for Cdc20 in regulating trypanosomatid G2/M events, opening avenues for further research in this area. PMID- 27272907 TI - Clinical prediction of large vessel occlusion in anterior circulation stroke: mission impossible? AB - Simple clinical scores to predict large vessel occlusion (LVO) in acute ischemic stroke would be helpful to triage patients in the prehospital phase. We assessed the ability of various combinations of National Institutes of Health Stroke Scale (NIHSS) subitems and published stroke scales (i.e., RACE scale, 3I-SS, sNIHSS-8, sNIHSS-5, sNIHSS-1, mNIHSS, a-NIHSS items profiles A-E, CPSS1, CPSS2, and CPSSS) to predict LVO on CT or MR arteriography in 1085 consecutive patients (39.4 % women, mean age 67.7 years) with anterior circulation strokes within 6 h of symptom onset. 657 patients (61 %) had an occlusion of the internal carotid artery or the M1/M2 segment of the middle cerebral artery. Best cut-off value of the total NIHSS score to predict LVO was 7 (PPV 84.2 %, sensitivity 81.0 %, specificity 76.6 %, NPV 72.4 %, ACC 79.3 %). Receiver operating characteristic curves of various combinations of NIHSS subitems and published scores were equally or less predictive to show LVO than the total NIHSS score. At intersection of sensitivity and specificity curves in all scores, at least 1/5 of patients with LVO were missed. Best odds ratios for LVO among NIHSS subitems were best gaze (9.6, 95 %-CI 6.765-13.632), visual fields (7.0, 95 %-CI 3.981-12.370), motor arms (7.6, 95 %-CI 5.589-10.204), and aphasia/neglect (7.1, 95 %-CI 5.352 9.492). There is a significant correlation between clinical scores based on the NIHSS score and LVO on arteriography. However, if clinically relevant thresholds are applied to the scores, a sizable number of LVOs are missed. Therefore, clinical scores cannot replace vessel imaging. PMID- 27272908 TI - Abyssicoccus albus gen. nov., sp. nov., a novel member of the family Staphylococcaceae isolated from marine sediment of the Indian Ocean. AB - A Gram-stain positive, aerobic, non-motile, asporogenous, coccoid shaped bacterium, designated YIM M12140(T), was isolated from a marine sediment sample collected from the Indian Ocean. Phylogenetic analysis showed that strain YIM M12140(T) forms a separate clade within the family Staphylococcaceae. Strain YIM M12140(T) shares high 16S rRNA gene sequence similarity with Macrococcus brunensis DSM 19358(T) (92.9 %). The isolate was found to grow at 0-10 % (w/v) NaCl (optimum, 2-3 %), pH 6.0-10.0 (optimum, pH 8.0) and temperature 5-40 degrees C (optimum, 28 degrees C). The polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophospholipid and two unidentified polar lipids. The major cellular fatty acids of the strain were identified as anteiso-C15:0, -C17:0, iso-C16:0, anteiso-C19:0 and C20:0. The respiratory menaquinones were found to be MK-6 (94 %) and MK-7 (6 %). The cell wall amino acids were found to contain Lys, Ala, Glu, Gly, Asp, Ser and Thr. Whole cell sugars were identified as mannose, ribose, rhamnose, glucose, galactose and xylose. The G+C content of the genomic DNA of strain YIM M12140(T) was determined to be 42.4 mol %. Based on phenotypic, chemotaxonomic data and phylogenetic analysis, it is proposed that strain YIM M12140(T) represents a novel species of a new genus in the family Staphylococcaceae, for which the name Abyssicoccus albus gen. nov., sp. nov. is proposed. The type strain is YIM M12140(T) (= DSM 29158(T) = CCTCC AB 2014213(T)). PMID- 27272910 TI - Tissue culture on a chip: Developmental biology applications of self-organized capillary networks in microfluidic devices. AB - Organ culture systems are used to elucidate the mechanisms of pattern formation in developmental biology. Various organ culture techniques have been used, but the lack of microcirculation in such cultures impedes the long-term maintenance of larger tissues. Recent advances in microfluidic devices now enable us to utilize self-organized perfusable capillary networks in organ cultures. In this review, we will overview past approaches to organ culture and current technical advances in microfluidic devices, and discuss possible applications of microfluidics towards the study of developmental biology. PMID- 27272911 TI - Children with cancer share their views: tell the truth but leave room for hope. AB - AIM: One in five children diagnosed with cancer will die from the disease. The aim of the study was to explore how children with cancer want to receive bad news about their disease, such as when no more treatment options are available. METHODS: We conducted individual interviews with ten children with cancer, aged seven to 17 years, at a single paediatric oncology unit in central Sweden. Interviews were audio-taped and analysed with systematic text condensation. Bad news was defined as information about a potentially fatal outcome, such as a disease relapse, or information that the treatment administered was no longer working and that there was no more treatment possible. RESULTS: All children expressed that they wanted truthful information and they did not want to be excluded from bad news regarding their illness. They wanted to be informed as positively as possible, allowing them to maintain hope, and in words that they could understand. They also wanted to receive any bad news at the same time as their parents. CONCLUSION: Children with cancer want to be fully informed about their disease, but they also wanted it to be relayed as positively as possible so that they could stay hopeful. PMID- 27272913 TI - Immunocryosurgery - an effective combinational modality for Bowen's disease. AB - Bowen's disease (BD) is widely treated with topical imiquimod or cryosurgery. The present single-center retrospective study reports on the application of standardized immunocryosurgery (cryosurgery during ongoing topical imiquimod) for the treatment of BD. Daily imiquimod 5% cream was applied on BD lesion and a 5 mm rim around it in 5-week treatment cycles; cryosurgery (liquid N2 , open spray; 2 cycles, 15 second each) was performed at the end of the second week of each treatment cycle. Between 1/1/2009 and 31/12/2014 21 patients (mean age +/- SD: 74.4 +/- 8.0 years; 12 males) with 24 lesions (mean maximum diameter +/- SD: 45.8 +/- 50.9 mm; range: 9-200 mm) completed the protocol. The anatomic distribution of the lesions included face/scalp (Nu = 14), neck/trunk (Nu = 6), and extremities (Nu = 4). Twenty-one out of twenty-four lesions with diameter <80 mm cleared after one immunocryosurgery cycle, while the rest three tumors (with the largest diameters: 100, 180, 200 mm) required two treatment cycles for complete response (clearance rate: 100%). After a median follow-up of 24 months (range: 6 60 months) the overall effectiveness was 91.7%: 22/24 lesions remained in sustained complete remission. With the exception of a variable degree of hypopigmentation, the cosmetic outcome was satisfactory even for extensive lesions. Immunocryosurgery, is feasible and highly efficacious minimally-invasive treatment alternative for BD. PMID- 27272912 TI - What Online User Innovation Communities Can Teach Us about Capturing the Experiences of Patients Living with Chronic Health Conditions. A Scoping Review. AB - BACKGROUND: In order to adapt to societal changes, healthcare systems need to switch from a disease orientation to a patient-centered approach. Virtual patient networks are a promising tool to favor this switch and much can be learned from the open and user innovation literature where the involvement of online user communities in the innovation process is well-documented. OBJECTIVES: The objectives of this study were 1) to describe the use of online communities as a tool to capture and harness innovative ideas of end users or consumers; and 2) to point to the potential value and challenges of these virtual platforms to function as a tool to inform and promote patient-centered care in the context of chronic health conditions. METHODS: A scoping review was conducted. A total of seven databases were searched for scientific articles published in English between 1995 and 2014. The search strategy was refined through an iterative process. RESULTS: A total of 144 studies were included in the review. Studies were coded inductively according to their research focus to identify groupings of papers. The first set of studies focused on the interplay of factors related to user roles, motivations, and behaviors that shape the innovation process within online communities. Studies of the second set examined the role of firms in online user innovation initiatives, identifying different organizational strategies and challenges. The third set of studies focused on the idea selection process and measures of success with respect to online user innovation initiatives. Finally, the findings from the review are presented in the light of the particularities and challenges discussed in current healthcare research. CONCLUSION: The present paper highlights the potential of virtual patient communities to inform and promote patient-centered care, describes the key challenges involved in this process, and makes recommendations on how to address them. PMID- 27272914 TI - Sequential protein extraction as an efficient method for improved proteome coverage in larvae of Atlantic salmon (Salmo salar). AB - Understanding diet- and environmentally induced physiological changes in fish larvae is a major goal for the aquaculture industry. Proteomic analysis of whole fish larvae comprising multiple tissues offers considerable potential but is challenging due to the very large dynamic range of protein abundance. To extend the coverage of the larval phase of the Atlantic salmon (Salmo salar) proteome, we applied a two-step sequential extraction (SE) method, based on differential protein solubility, using a nondenaturing buffer containing 150 mM NaCl followed by a denaturing buffer containing 7 M urea and 2 M thiourea. Extracts prepared using SE and one-step direct extraction were characterized via label-free shotgun proteomics using nanoLC-MS/MS (LTQ-Orbitrap). SE partitioned the proteins into two fractions of approximately equal amounts, but with very distinct protein composition, leading to identification of ~40% more proteins than direct extraction. This fractionation strategy enabled the most detailed characterization of the salmon larval proteome to date and provides a platform for greater understanding of physiological changes in whole fish larvae. The MS data are available via the ProteomeXchange Consortium PRIDE partner repository, dataset PXD003366. PMID- 27272915 TI - Blowing smoke: the history of tobacco-specific nitrosamines in Canadian tobacco. AB - OBJECTIVE: To demonstrate how changes in tobacco flue-curing practices in the 20th century increased levels of tobacco-specific nitrosamines (TSNAs) in tobacco smoke. METHODS: Previously undisclosed documents and testimony made public as a result of a class action trial against tobacco companies in Montreal, Canada, were reviewed for information on TSNAs and tobacco curing practices. These were combined with other pertinent documents to form the basis for a comprehensive historical review of TSNAs and tobacco curing practices. RESULTS: In the 1960s and 1970s, a change was made from indirect heating to direct heating for flue curing tobacco that resulted in an increase in the TSNA-to-tar ratio in flue cured tobacco. This occurred in both Canada and the USA. When this change was made, tobacco companies did not monitor for increased levels of TSNAs and did not study possible adverse effects on human health. As a result, smokers were unknowingly exposed to unnecessarily high levels of TSNAs for 30-40 years. In recent years, tobacco companies have changed curing practices back to indirect heating, thus returning the TSNA-to-tar ratios in tobacco smoke to their previously low levels. CONCLUSIONS: In view of this information brought to light in this paper, any claims by tobacco companies that they were acting prudently by lowering TSNA levels are unwarranted. They fail to acknowledge that it was their actions that raised TSNA levels in the first place about half a century ago. PMID- 27272916 TI - Kinetic therapy in multiple trauma patients with severe thoracic trauma: a treatment option to reduce ventilator time and improve outcome. AB - PURPOSE: Continuous lateral rotational therapy (CLRT) has been described as a promising approach for prophylaxis and treatment of respiratory complications in critically ill patients over two decades ago. However, meta-analyses failed to demonstrate any significant benefit on outcome by CLRT, possibly due to the heterogeneity and low overall quality of available studies. METHODS: Observational trial over a 3-year period on outcome in trauma patients (Injury Severity Score, ISS >=16) with severe thoracic injury (Abbreviated Injury Scale, AISThorax >=3) initially treated with CLRT as standard of care. Epidemiological data, injury severity, and pattern and physiological parameters were recorded. Outcome indicators were time on mechanical ventilation, length of stay, rates of pneumonia, sepsis and acute respiratory distress syndrome, hospital mortality, and rates of re-intubation. Additionally, data are compared with the results from the TraumaRegister(r) of the German Trauma Society. RESULTS: Over the 3-year period 76 patients with ISS >=16/AISThorax >=3 received CLRT, equaling 24 % of all patients with ISS >=16 between 18 and 80 years. Mean ISS was 35.3 (standard deviations, SD 12.2) [71.1 % male, 97.4 % blunt trauma, mean age 43.9 years (SD 18.7)]. Mean time on CLRT was 3.3 days (SD 2.2), time on mechanical ventilation 7.8 days (SD 7.1), and 9.2 % had to be re-intubated due to respiratory complications. CLRT-related complications occurred in 8.9 %. Overall 25 % of the patients developed pneumonia (VAP = 13.2 %). Despite a significantly higher ISS we observed shorter times on mechanical ventilation and intensive care unit in our collective in comparison to data published from the nationwide TraumaRegister(r). CONCLUSIONS: CLRT remains a therapeutic option to reduce pulmonary complications after severe chest trauma in our center. However, a RCT is needed to study the effects of other treatment options such as early extubation and non-invasive ventilation or prone/supine positioning. PMID- 27272917 TI - Evaluation of efficacy and indications of surgical fixation for multiple rib fractures: a propensity-score matched analysis. AB - PURPOSE: The purpose of this study was to assess the effects of recent surgical rib fixation and establish its indications not only for flail chest but also for multiple rib fractures. METHODS: Between 2007 and 2015, 187 patients were diagnosed as having multiple rib fractures in our institution. After the propensity score matching was performed, ten patients who had performed surgical rib fixation and ten patients who had treated with non-operative management were included. Categorical variables were analyzed with Fischer's exact test and non parametric numerical data were compared using the Mann-Whitney U test. Wilcoxon signed-rank test was performed for comparison of pre- and postoperative variables. All statistical data are presented as median (25-75 % interquartile range [IQR]) or number. RESULTS: The surgically treated patients extubated significantly earlier than non-operative management patients (5.5 [1-8] vs 9 [7 12] days: p = 0.019). The duration of continuous intravenous narcotic agents infusion days (4.5 [3-6] vs 12 [9-14] days: p = 0.002) and the duration of intensive care unit stay (6.5 [3-9] vs 12 [8-14] days: p = 0.008) were also significantly shorter in surgically treated patients. Under the same ventilating conditions, the postoperative values of tidal volume and respiratory rate improved significantly compared to those values measured just before the surgery. The incidence of pneumonia as a complication was significantly higher in non operative management group (p = 0.05). CONCLUSIONS: From the viewpoints of early respiratory stabilization and intensive care unit disposition without any complications, surgical rib fixation is a sufficiently acceptable procedure not only for flail chest but also for repair of severe multiple rib fractures. PMID- 27272918 TI - Heavy metal bioaccumulation by wild edible saprophytic and ectomycorrhizal mushrooms. AB - Heavy metals cause serious problems in the environment, and they can be accumulated in organisms, especially in the higher fungi. The concentration of Ni, Cr, Pb, Cd, and Hg in 10 species of edible mushrooms in Medvednica Nature Park, Croatia was therefore determined. In addition, the similarity between the studied species was determined by cluster analysis based on concentrations of the aforementioned metals in the fruiting bodies. The contents of nickel, chromium, lead, cadmium, and mercury in the fruiting bodies of mushrooms were obtained by X ray fluorescence spectrometry. The highest concentrations of Ni (3.62 mg kg(-1)), Cr (3.01 mg kg(-1)), and Cd (2.67 mg kg(-1)) were determined in Agaricus campestris. The highest concentration of Pb (1.67 mg kg(-1)) was determined in Macrolepiota procera, and the highest concentration of Hg (2.39 mg kg(-1)) was determined in Boletus edulis. The concentration of all heavy metals significantly differed (p < 0.001) between examined saprophytic and ectomycorrhizal mushrooms. Considering anatomical part of the fruiting body (cap-stipe), a considerably higher concentration of the analyzed elements was found in the cap for all mushroom species. According to calculated bioconcentration factors, all the examined species were found to be bioexclusors of Ni, Cr, and Pb and bioaccumulators of Cd and Hg. Cluster analysis performed on the basis of the accumulation of the studied metals revealed great phenotypic similarity of mushroom species belonging to the same genus and partial similarity of species of the same ecological affiliation. PMID- 27272919 TI - Forest floor decomposition, metal exchangeability, and metal bioaccumulation by exotic earthworms: Amynthas agrestis and Lumbricus rubellus. AB - Earthworms have the potential to reduce the retention of pollutant and plant essential metals in the forest floor (organic horizons) by decomposing organic matter and increasing exchangeability of metals. We conducted a laboratory experiment to investigate the effects of two exotic earthworms, Amynthas agrestis and Lumbricus rubellus, on forest floor decomposition, metal exchangeability, and metal bioaccumulation. Eighty-one pots containing homogenized forest floor material were incubated for 20, 40, or 80 days under three treatments: no earthworms, A. agrestis added, or L. rubellus added. For earthworm treatments, A. agrestis and L. rubellus were stocked at densities observed in previous field studies. Pots containing either A. agrestis or L. rubellus had lost more forest floor mass than the control plots after 40 and 80 days of incubation. Forest floor pots containing A. agrestis had significantly lower % C (16 +/- 1.5 %) than control pots (21 +/- 1.2 %) after 80 days. However, L. rubellus consumed more forest floor and C mass than A. agrestis, when evaluated on a per earthworm biomass basis. Exchangeable (0.1 M KCl + 0.01 M AcOH extractable) and stable (15 M HNO3+ 10 M HCl extractable) concentrations of Al, Ca, Cd, Cu, Mg, Mn, Pb, and Zn in forest floor material were measured. Stable concentrations and % exchangeable metals in forest floor material were similar among treatments. Although exchangeable metal concentrations varied significantly for most metals among treatments (except Mg and Zn), we conclude that earthworms did not increase or decrease the exchangeability of metals. However, earthworms bioaccumulated Cu, Cd, Zn, and Mg and had potentially hazardous tissue concentrations of Al and Pb. This was best illustrated by calculating bioaccumulation factors using exchangeable concentrations rather than total concentrations. Future research is needed to understand the effect of earthworms on metals in other soil types. PMID- 27272920 TI - Toxic pollution threatens migratory shorebirds in India. PMID- 27272923 TI - Non-lead ammunition may reduce lead levels in wild game. PMID- 27272921 TI - Application of a multidisciplinary and integrative weight-of-evidence approach to a 1-year monitoring survey of the Seine River. AB - Quality assessment of environments under high anthropogenic pressures such as the Seine Basin, subjected to complex and chronic inputs, can only be based on combined chemical and biological analyses. The present study integrates and summarizes a multidisciplinary dataset acquired throughout a 1-year monitoring survey conducted at three workshop sites along the Seine River (PIREN-Seine program), upstream and downstream of the Paris conurbation, during four seasonal campaigns using a weight-of-evidence approach. Sediment and water column chemical analyses, bioaccumulation levels and biomarker responses in caged gammarids, and laboratory (eco)toxicity bioassays were integrated into four lines of evidence (LOEs). Results from each LOE clearly reflected an anthropogenic gradient, with contamination levels and biological effects increasing from upstream to downstream of Paris, in good agreement with the variations in the structure and composition of bacterial communities from the water column. Based on annual average data, the global hazard was summarized as "moderate" at the upstream station and as "major" at the two downstream ones. Seasonal variability was also highlighted; the winter campaign was least impacted. The model was notably improved using previously established reference and threshold values from national-scale studies. It undoubtedly represents a powerful practical tool to facilitate the decision-making processes of environment managers within the framework of an environmental risk assessment strategy. PMID- 27272924 TI - BTX in urban areas of eastern Spain: a focus on time variations and sources. AB - Seasonal and daily cycles of BTX were studied in a non-industrialized city (Alicante) and an urban area near an oil refinery plant (Castellon) in order to evaluate the influence of different sources on time variations. Lower levels were observed in summer than in winter at both locations due to higher dispersion conditions and photochemical removal of BTX during the summer season. Daily patterns showed seasonal differences and were controlled by traffic emissions and the evolution of the mixing layer height, with no influence of the petroleum refinery plant in the city of Castellon. The results of the conditional bivariate probability function suggest that the influence of this source on BTX concentrations was limited to point impacts. At both sites, benzene exhibited a different behavior from toluene and xylenes, most likely due to its significantly lower chemical reactivity. PMID- 27272922 TI - Perspectives of using fungi as bioresource for bioremediation of pesticides in the environment: a critical review. AB - Pesticides are used for controlling the development of various pests in agricultural crops worldwide. Despite their agricultural benefits, pesticides are often considered a serious threat to the environment because of their persistent nature and the anomalies they create. Hence removal of such pesticides from the environment is a topic of interest for the researchers nowadays. During the recent years, use of biological resources to degrade or remove pesticides has emerged as a powerful tool for their in situ degradation and remediation. Fungi are among such bioresources that have been widely characterized and applied for biodegradation and bioremediation of pesticides. This review article presents the perspectives of using fungi for biodegradation and bioremediation of pesticides in liquid and soil media. This review clearly indicates that fungal isolates are an effective bioresource to degrade different pesticides including lindane, methamidophos, endosulfan, chlorpyrifos, atrazine, cypermethrin, dieldrin, methyl parathion, heptachlor, etc. However, rate of fungal degradation of pesticides depends on soil moisture content, nutrient availability, pH, temperature, oxygen level, etc. Fungal strains were found to harbor different processes including hydroxylation, demethylation, dechlorination, dioxygenation, esterification, dehydrochlorination, oxidation, etc during the biodegradation of different pesticides having varying functional groups. Moreover, the biodegradation of different pesticides was found to be mediated by involvement of different enzymes including laccase, hydrolase, peroxidase, esterase, dehydrogenase, manganese peroxidase, lignin peroxidase, etc. The recent advances in understanding the fungal biodegradation of pesticides focusing on the processes, pathways, genes/enzymes and factors affecting the biodegradation have also been presented in this review article. PMID- 27272926 TI - BaCdSnS4 and Ba3CdSn2S8: syntheses, structures, and non-linear optical and photoluminescence properties. AB - Two non-centrosymmetric metal chalcogenides, BaCdSnS4 and Ba3CdSn2S8, were synthesized using a high temperature solid-state reaction in an evacuated silica tube. Although the two compounds have the same building units in their structures, namely CdS4, SnS4 and BaS8 units, both of them have different structures. BaCdSnS4 crystallizes in the orthorhombic space group Fdd2 and its structure can be characterized by the two-dimensional infinity[Cd-Sn-S] layers composed of corner- and edge-sharing CdS4 and SnS4 tetrahedra with Ba atoms located between the two adjacent infinity[Cd-Sn-S] layers. Ba3CdSn2S8 crystallizes in the space group I4[combining macron]3d of the orthorhombic system and the CdS4 and SnS4 groups are connected with each other via corner-sharing to form a three-dimensional framework, which is different from the 2D infinity[Cd-Sn S] layer structure in BaCdSnS4. The UV-vis-NIR diffuse-reflectance spectra show that the experimental band gaps are about 2.30 eV for BaCdSnS4 and 2.75 eV for Ba3CdSn2S8, respectively. IR and Raman measurement results indicate that their transparent ranges are up to 25 MUm. Second-order NLO measurements show that BaCdSnS4 exhibits strong powder second-harmonic generation (SHG) intensities at 2.09 MUm laser pumping that are ~5 and 0.7 times that of AgGaS2 in the particle size 38-55 and 150-200 MUm, respectively, whereas Ba3CdSn2S8 only exhibits SHG intensities of about 0.8 and 0.1 times that of AgGaS2 at the same particle sizes. The origin of the NLO response in BaCdSnS4 may originate from the macroscopic arrangement of the SnS4 and CdS4 tetrahedra. Furthermore, the photoluminescence properties of the two compounds have also been investigated and show obvious blue and green light emission. PMID- 27272925 TI - Vinegar residue compost as a growth substrate enhances cucumber resistance against the Fusarium wilt pathogen Fusarium oxysporum by regulating physiological and biochemical responses. AB - Fusarium wilt caused by the fungus Fusarium oxysporum f. sp. cucumerinum (FOC) is the most severe soil-borne disease attacking cucumber. To assess the positive effects of vinegar residue substrate (VRS) on the growth and incidence of Fusarium wilt on cucumber, we determined the cucumber growth parameters, disease severity, defense-related enzyme and pathogenesis-related (PR) protein activities, and stress-related gene expression levels. In in vitro and pot experiments, we demonstrated the following results: (i) the VRS extract exhibited a higher biocontrol activity than that of peat against FOC, and significantly improved the growth inhibition of FOC, with values of 48.3 %; (ii) in response to a FOC challenge, antioxidant enzymes and the key enzymes of phenylpropanoid metabolic activities, as well as the PR protein activities in the roots of cucumber, were significantly increased. Moreover, the activities of these proteins were higher in VRS than in peat; (iii) the expression levels of stress related genes (including glu, pal, and ethylene receptor) elicited responses to the pathogens inoculated in cucumber leaves; and (iv) the FOC treatment significantly inhibited the growth of cucumber seedlings. Moreover, all of the growth indices of plants grown in VRS were significantly higher than those grown in peat. These results offer a new strategy to control cucumber Fusarium wilt, by upregulating the activity levels of defense-related enzymes and PR proteins and adjusting gene expression levels. They also provide a theoretical basis for VRS applications. PMID- 27272928 TI - Variables decreasing tip movement of peripherally inserted central catheters in pediatric patients. AB - BACKGROUND: The position of the tip of a peripherally inserted central catheter (PICC) is crucial; malposition can lead to malfunction of the line or life threatening events (e.g., arrhythmias, perforation). OBJECTIVE: To determine what factors other than arm position and accessed vein might influence the tip position of a PICC. MATERIALS AND METHODS: Inclusion criteria were upper limb PICC placement, body weight <20 kg, intraoperative imaging with the arm in 0 degrees , 45 degrees and 90 degrees abduction and an arm view marking the skin entry site relative to the shoulder. Evaluated variables included patient demographics, and PICC and insertion site characteristics. We measured central tip movement in rib units. RESULTS: We included 112 children who received a PICC (42 girls/70 boys, mean age 31+/-13 months, mean weight 6.5+/-4.9 kg). The overall range of central tip movement was -1 to +4 rib units (mean +0.8+/-0.7 rib units). Silicone PICCs moved significantly less than polyurethane PICCs (P<0.05). PICCs placed in the cephalic vein moved significantly less than those placed in other veins (P<0.05). Patient demographics and PICC characteristics (size, number of lumens, left or right arm accessed, length of the line) did not influence the range of central tip movement of a PICC (P>0.05). CONCLUSION: Silicone PICCs and PICCs inserted into the cephalic vein move less than PICCs made of polyurethane and PICCs inserted into the brachial and basilic veins. These findings might assist operators in deciding which PICC to place in children in a given clinical context. PMID- 27272930 TI - Pd-Catalyzed C-H Alkylation of Arenes Using PyrDipSi, a Transformable and Removable Silicon-Tethered Directing Group. AB - An efficient Pd-catalyzed ortho-C-H alkylation reaction of arenes using a transformable and removable Si-tethered pyridyldiisopropylsilyl (PyrDipSi) directing group has been developed. In addition, the PyrDipSi directing group allows for an efficient sequential double-fold C-H alkylation/oxygenation of arenes to produce meta-alkylated phenols. This directing group can easily be removed or converted into valuable functionalities, such as aryl, iodo, boronic ester, or phenol. PMID- 27272929 TI - Linking Bacillus cereus Genotypes and Carbohydrate Utilization Capacity. AB - We characterised carbohydrate utilisation of 20 newly sequenced Bacillus cereus strains isolated from food products and food processing environments and two laboratory strains, B. cereus ATCC 10987 and B. cereus ATCC 14579. Subsequently, genome sequences of these strains were analysed together with 11 additional B. cereus reference genomes to provide an overview of the different types of carbohydrate transporters and utilization systems found in B. cereus strains. The combined application of API tests, defined growth media experiments and comparative genomics enabled us to link the carbohydrate utilisation capacity of 22 B. cereus strains with their genome content and in some cases to the panC phylogenetic grouping. A core set of carbohydrates including glucose, fructose, maltose, trehalose, N-acetyl-glucosamine, and ribose could be used by all strains, whereas utilisation of other carbohydrates like xylose, galactose, and lactose, and typical host-derived carbohydrates such as fucose, mannose, N-acetyl galactosamine and inositol is limited to a subset of strains. Finally, the roles of selected carbohydrate transporters and utilisation systems in specific niches such as soil, foods and the human host are discussed. PMID- 27272931 TI - Live-cell quantification and comparison of mammalian oocyte cytosolic lipid content between species, during development, and in relation to body composition using nonlinear vibrational microscopy. AB - Cytosolic lipids participate in the growth, development, and overall health of mammalian oocytes including many roles in cellular homeostasis. Significant emphasis has been placed on the study of lipids as a dynamic organelle, which in turn requires the development of tools and techniques to quantitate and compare how lipid content relates to cellular structure, function, and normalcy. Objectives of this study were to determine if nonlinear vibrational microscopy (e.g., coherent anti-Stokes Raman scattering or CARS microscopy) could be used for live-cell imaging to quantify and compare lipid content in mammalian oocytes during development and in relation to body composition; and compare its efficacy to methods involving cellular fixation and staining protocols. Results of this study demonstrate that CARS is able to identify lipids in live mammalian oocytes, and there exists quantifiable and consistent differences in percent lipid composition across ooctyes of different species, developmental stages, and in relation to body composition. Such a method of live-cell lipid quantification has (i) experimental power in basic cell biology, (ii) practical utility for identifying developmental predictive biomarkers while advancing biology-based oocyte/embryo selection, and (iii) ability to yield rationally supporting technology for decision-making in rodents, domestic species, and human assisted reproduction and/or fertility preservation. PMID- 27272932 TI - Reproductive coercion, sexual risk behaviours and mental health symptoms among young low-income behaviourally bisexual women: implications for nursing practice. AB - AIMS AND OBJECTIVES: To describe prevalence of reproductive coercion, sexual risk behaviours and mental health symptoms among women reporting lifetime sexual experiences with men and women compared to peers reporting sex exclusively with men. BACKGROUND: Reproductive coercion, a global public health problem, is understudied among sexual minority women. Violence against women remains high among women who have sex with women and men. Rates of sexual and physical violence among this population are higher than women reporting exclusive sexual partnerships with either men or women. Nurses and other healthcare providers often do not conduct comprehensive sexual histories; assumptions related to a sex partner's gender may provide indications of broader health implications. DESIGN: Cross-sectional survey of low-income Black women ages 18-25 recruited from six community-based sites for a parent study focused on intimate partner violence and health. METHODS: We analysed survey data from participants who reported lifetime sexual experiences with men and women (N = 42) and compared their outcomes to those of women reporting sexual experiences with men only (N = 107). RESULTS: A greater proportion of women who have sex with women and men reported experiencing reproductive coercion. Women who have sex with women and men also reported a greater number of lifetime intimate partner physical and sexual violence experiences, traded sex for resources, and had post-traumatic stress disorder symptoms. CONCLUSIONS: Findings provide vital information that can inform nursing clinical practice, specifically related to history-taking, screening protocols and counselling strategies for intimate partner violence and mental health among women who have sex with women and men. RELEVANCE TO CLINICAL PRACTICE: Strategies for addressing reproductive coercion and intimate partner violence as well as the health consequences among women who have sex with women and men in clinical and community-based settings should include a longitudinal understanding of sexual behaviour and gender of sex partners. PMID- 27272933 TI - A comparison of vertebral venous networks in adolescent idiopathic scoliosis patients and healthy controls. AB - PURPOSE: Cadaveric studies have previously documented a typical pattern of venous drainage within vertebral bodies (VBs), comprised primarily of the basivertebral vein. These studies, however, are limited by the number of samples available. MRI is able to provide 3D images of soft tissue structures in the spine, including the basivertebral vein without the use of contrast in both healthy controls and subjects with abnormal anatomy such as adolescent idiopathic scoliosis (AIS). This study aimed to quantify the venous networks within VBs of 15 healthy adolescent controls and 15 AIS patients. METHODS: Five transverse slices through the VBs were examined simultaneously and the observable vascular network traced. The length of the network on the left and right sides of the VB was calculated, and the spatial patterning assessed level-by-level within each subject. RESULTS: Significant differences were seen in the left/right distribution of vessels in both the control and AIS subjects, with both groups having greater length on the right side of all of their VBs. No difference was seen between AIS and control subjects in any region. Large individual variations in patterns were seen in both groups; however, the control group showed more consistent spatial patterning of the vascular networks across levels in comparison to the AIS group. CONCLUSION: The length of the basivertebral vein was seen to have a significant bias to the right hand side of the VB in both healthy and AIS adolescents. The spatial pattern of this vein showed large variations in branching both within and across individuals. No significant differences were seen between AIS and control subjects, suggesting both that this network is preserved in deformed AIS vertebrae, and that the vertebral venous system does not play a role in the etiology of AIS. PMID- 27272934 TI - ABPM Induced Alarm Reaction: A Possible Cause of Overestimation of Daytime Blood Pressure Values Reduced By Treatment with Beta-Blockers. AB - INTRODUCTION: Alarm reaction to clinical blood pressure (BP) measurement, defined white-coat effect (WCE), can cause overestimation of true BP values. AIM: To assess whether ambulatory blood pressure monitoring (ABPM) can similarly affect BP values during the initial hours of recording. METHODS: In 420 ABPMs selected for a first systolic BP (SBP) reading at least 10 mmHg higher than the mean daytime SBP, we calculated mean diurnal and 24 h SBP with and without the exclusion of the two first hours of recording defined as the WCE window (WCEw). We also calculated the magnitude and duration of WCE. These analyses were also performed separately in patients off anti-hypertensive treatment (n = 156), and on treatment with and without the inclusion of beta-blockers (respectively n = 113 and 151). RESULTS: Exclusion of WCEw period reduced mean diurnal and 24 h SBP respectively from 135 +/- 0.5 to 133 +/- 0.5 (p < 0.01) and from 131 +/- 0.5 to 130 +/- 0.5 (p < 0.02). As a result the percentage of patients diagnosed as having diurnal or 24 h hypertension was reduced respectively from 48 to 40 % and from 52 to 47 %. The magnitude of WCEw was similar in both genders but the duration was longer in females (66 +/- 2 vs. 56 +/- 2 min, p < 0.01). Treatment with beta-blockers was associated with a shorter duration of WCE in both genders but this effect was statistically significant only in males. CONCLUSIONS: In some patients ABPM is not free from WCE. WCE may affect the overall estimation of BP profile and is longer but less blunted by beta-blockers in females than in males. PMID- 27272935 TI - Computer-aided detection of prostate cancer in T2-weighted MRI within the peripheral zone. AB - In this paper we propose a prostate cancer computer-aided diagnosis (CAD) system and suggest a set of discriminant texture descriptors extracted from T2-weighted MRI data which can be used as a good basis for a multimodality system. For this purpose, 215 texture descriptors were extracted and eleven different classifiers were employed to achieve the best possible results. The proposed method was tested based on 418 T2-weighted MR images taken from 45 patients and evaluated using 9-fold cross validation with five patients in each fold. The results demonstrated comparable results to existing CAD systems using multimodality MRI. We achieved an area under the receiver operating curve (A z ) values equal to [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] for Bayesian networks, ADTree, random forest and multilayer perceptron classifiers, respectively, while a meta-voting classifier using average probability as a combination rule achieved [Formula: see text]. PMID- 27272937 TI - Home-based walking during pregnancy affects mood and birth outcomes among sedentary women: A randomized controlled trial. AB - We examined the effects of home-based walking on sedentary Japanese women's pregnancy outcomes and mood. A randomized controlled trial was conducted, involving 118 women aged 22-36 years. Participants were randomly assigned to walking intervention (n = 60) or control (n = 58) groups. The walking group was instructed to walk briskly for 30 min, three times weekly from 30 weeks' gestation until delivery. Both groups counted their daily steps using pedometers. Pregnancy and delivery outcomes were assessed, participants completed the Profile of Mood States, and we used the intention-to-treat principle. Groups showed no differences regarding pregnancy or delivery outcomes. The walking group exhibited decreased scores on the depression-dejection and confusion subscales of the Profile of Mood States. Five of the 54 women in the intervention group who remained in the study (9.2%) completed 100% of the prescribed walking program; 32 (59.3%) women completed 80% or more. Unsupervised walking improves sedentary pregnant women's mood, indicating that regular walking during pregnancy should be promoted in this group. PMID- 27272939 TI - Opportunities and challenges of 2D magnetic van der Waals materials: magnetic graphene? PMID- 27272938 TI - Low-level Chronic Lead Exposure Impairs Neural Control of Blood Pressure and Heart Rate in Rats. AB - Lead (Pb) induces adverse effects when it chronically accumulates in the body, including effects on the nervous and cardiovascular systems. Wistar rats were exposed to lead acetate for 30 days (first dose 4 ug/100 g followed by 0.05 ug/100 g/day, i.m.) to investigate the cardiovascular system impact on the autonomic control. The femoral artery and vein were catheterised to perform hemodynamic evaluations in awake rats: heart rate variability (HRV), baroreflex sensitivity, cardiopulmonary reflex and hemodynamic responses to vagal and sympathetic pharmacological blockade. Rats exposed to Pb exhibited a higher blood pressure and reduced HRV in the time domain when compared to the saline-injected group. Spectral analysis of the HRV in the frequency-domain showed an augmented low-frequency component of the spectrum. Methylatropine and atenolol administration suggest increased sympathetic tone and reduced vagal tone on the control of heart rate. Chronic Pb exposure decreased the sensitivity of the baroreflex without significantly changing the cardiopulmonary reflex. This study demonstrated for the first time in an animal model of a controlled, low-dose chronic lead exposure that cardiovascular changes, such as arterial hypertension, are accompanied by impaired autonomic control of the cardiovascular system, as characterised by reduced baroreflex sensitivity and a sympathovagal imbalance. PMID- 27272936 TI - Category-Selectivity in Human Visual Cortex Follows Cortical Topology: A Grouped icEEG Study. AB - Neuroimaging studies suggest that category-selective regions in higher-order visual cortex are topologically organized around specific anatomical landmarks: the mid-fusiform sulcus (MFS) in the ventral temporal cortex (VTC) and lateral occipital sulcus (LOS) in the lateral occipital cortex (LOC). To derive precise structure-function maps from direct neural signals, we collected intracranial EEG (icEEG) recordings in a large human cohort (n = 26) undergoing implantation of subdural electrodes. A surface-based approach to grouped icEEG analysis was used to overcome challenges from sparse electrode coverage within subjects and variable cortical anatomy across subjects. The topology of category-selectivity in bilateral VTC and LOC was assessed for five classes of visual stimuli-faces, animate non-face (animals/body-parts), places, tools, and words-using correlational and linear mixed effects analyses. In the LOC, selectivity for living (faces and animate non-face) and non-living (places and tools) classes was arranged in a ventral-to-dorsal axis along the LOS. In the VTC, selectivity for living and non-living stimuli was arranged in a latero-medial axis along the MFS. Written word-selectivity was reliably localized to the intersection of the left MFS and the occipito-temporal sulcus. These findings provide direct electrophysiological evidence for topological information structuring of functional representations within higher-order visual cortex. PMID- 27272940 TI - Protective effects of a Modified Vaccinia Ankara-based vaccine candidate against Crimean-Congo Haemorrhagic Fever virus require both cellular and humoral responses. AB - Crimean-Congo Haemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. There is no approved vaccine currently available against CCHF. The most promising candidate, which has previously been shown to confer protection in the small animal model, is a modified Vaccinia Ankara virus vector expressing the CCHF viral glycoprotein (MVA-GP). It has been shown that MVA-GP induces both humoral and cellular immunogenicity. In the present study, sera and T-lymphocytes were passively and adoptively transferred into recipient mice prior to challenge with CCHF virus. Results demonstrated that mediators from both arms of the immune system were required to demonstrate protective effects against lethal challenge. PMID- 27272941 TI - Elevated levels of miR-210 correlate with anemia in beta-thalassemia/HbE patients. AB - Ineffective erythropoiesis in beta-thalassemia patients is caused by the premature death of red blood cell precursors due to excess alpha-globin chains. As a consequence, patients develop chronic anemia and hypoxia. Upregulation of miR-210, a hypoxia-induced miRNA, has been shown to regulate globin gene expression and erythroid differentiation in beta-thalassemia/HbE erythroid progenitor cell culture. The present study examined whether the expression of miR 210 in circulation reflects the anemic condition in these patients. The level of miR-210 expression was directly examined from red blood cells and plasma of beta thalassemia/HbE patients. Transferrin receptor, a marker of erythropoiesis activity, was also analyzed. Increased expression of both red blood cells and plasma miR-210 as well as elevated levels of serum transferrin receptor in beta thalassemia/HbE patients were observed when compared to those of normal individuals (p < 0.05). In addition, red blood cell miR-210 level was inversely correlated with hemoglobin levels (r = -0.7054, p < 0.01) and hematocrit (r = 0.6017, p < 0.05). The higher expression of miR-210 in these patients may be the consequence of hypoxia occurring from the lower hemoglobin level. Thus, analysis of red blood cell miR-210 may be useful as a method for assessing hypoxia in beta thalassemia patients. PMID- 27272944 TI - Genome-wide set of SNPs reveals evidence for two glacial refugia and admixture from postglacial recolonization in an alpine ungulate. AB - Past glaciation events have played a major role in shaping the genetic diversity and distribution of wild sheep in North America. The advancement of glaciers can isolate populations in ice-free refugia, where they can survive until the recession of ice sheets. The major Beringian refugium is thought to have held thinhorn sheep (Ovis dalli) populations during times of glacial advance. While isolation in the major refugium can account for much of the genetic and morphological diversity seen in extant thinhorn sheep populations, mounting evidence suggests the persistence of populations in smaller minor refugia. We investigated the refugial origins of thinhorn sheep using ~10 000 SNPs obtained via a cross-species application of the domestic sheep ovine HD BeadChip to genotype 52 thinhorn sheep and five bighorn sheep (O. canadensis) samples. Phylogenetic inference revealed a distinct lineage of thinhorn sheep inhabiting British Columbia, which is consistent with the survival of a group of thinhorn sheep in a minor refugium separate from the Beringian refugium. Isolation in separate glacial refugia probably mediated the evolution of the two thinhorn sheep subspecies, the white Dall's sheep (O. d. dalli), which persisted in Beringia, and the dark Stone's sheep (O. d. stonei), which utilized the minor refugium. We also found the first genetic evidence for admixture between sheep from different glacial refugia in south-central Yukon as a consequence of post glacial expansion and recolonization. These results show that glaciation events can have a major role in the evolution of species inhabiting previously glaciated habitats and the need to look beyond established refugia when examining the evolutionary history of such species. PMID- 27272943 TI - Fractional anisotropy in patients with disproportionately enlarged subarachnoid space hydrocephalus. AB - BACKGROUND: Disproportionately enlarged subarachnoid space hydrocephalus (DESH) findings on MRI were described as a prognostic factor for responsiveness to the treatment of idiopathic normal pressure hydrocephalus (iNPH). Our premise is that DESH could be associated with compression of the cerebral white matter. Microstructural changes can be identified using diffusion tensor imaging (DTI), specifically fractional anisotropy (FA). The aim of this study is to compare FA in iNPH patients with and without DESH and healthy controls. METHODS: We analysed 1.5-T MRI scans of patients fulfilling the criteria of probable or possible iNPH and positive supplementary tests before and after surgery (ventriculo-peritoneal shunt). FA was measured in the anterior and posterior limb of the internal capsule (PLIC) and in the corpus callosum. Patients were divided into the DESH and non-DESH group. These data were also compared to FA values in the control group. RESULTS: Twenty-seven patients and 24 healthy controls were enrolled. DESH was present in 15 patients and lacking in 12. Twenty-three iNPH patients were shunt responders (85.2 %), and 4 were non-responders (14.8 %). All patients in the DESH group were shunt responders. In the non-DESH group, eight patients were responders (66.7 %). A significant difference between the DESH and non-DESH group was found in the FA of the PLIC. The mean value of FA in the PLIC was 0.72 in the DESH group and 0.66 in the non-DESH group. After the surgery FA decreased in both groups. In the DESH iNPH group FA PLIC decreased to 0.65 and in the non-DESH iNPH group to 0.60. In the healthy controls, the mean FA in the PLIC was 0.58. CONCLUSION: DESH on MRI scans is related to a higher FA in the PLIC with a decrease after the surgery. It reflects a more severe compression of the white matter than in non-DESH patients or healthy volunteers. DESH patients had better outcome than non-DESH patients. This study confirmed the importance of DESH as a supportive sign for iNPH. PMID- 27272942 TI - High IL-7 levels in the bone marrow microenvironment mediate imatinib resistance and predict disease progression in chronic myeloid leukemia. AB - Chronic myeloid leukemia (CML) is a three-stage myeloproliferative disease caused by translocation between chromosomes 9 and 22. Although tyrosine kinase inhibitors (TKI) are highly effective in the treatment of CML, numerous clinical trials have shown that many patients become refractory or drug resistance, especially those in the blastic crisis of CML. The molecular mechanisms underlying CML, however, remain poorly understood. In the present study, we used a coculture model to address possible mechanisms underlying the involvement of bone marrow microenvironment in the drug resistance of CML. Our data show that interleukin-7(IL-7) levels in the bone marrow of CML patients in blastic crisis are significantly higher than those of both healthy persons and CML patients in chronic and accelerated phases. The increased IL-7 was secreted by mesenchymal stem cells (MSC) in the bone marrow, which may protect leukemic cells from apoptosis induced by imatinib through JAK1/STAT5 signaling pathway. Our findings suggest that therapeutic strategies IL-7 signaling pathway may represent a promising approach for improving CML therapy, especially for patients in blastic crisis. PMID- 27272947 TI - The deepithelialized skin flap for closure of large myelomeningoceles: a common plastic surgery technique for a novel neurosurgery application. AB - PURPOSE: The study aims to demonstrate proof of principle of a common plastic surgery technique of deepithelialization for repair of large myelomeningoceles (MMCs). Whereas repair typically consists of a watertight dural closure followed by a muscle or fasciocutaeneous layer, excess skin, however, need not be discarded and can be deepithelialized to augment or, in selective cases, replace the muscle repair. METHODS: The study was performed through a retrospective chart review of two patients. RESULTS: Step-by-step figures illustrate the technique. Two patients each born with large MMCs measuring 10 * 11 cm and 6 * 9 cm, respectively, were reviewed. Excess skin was deepithelialized to create an additional layer of vascularized tissue over the muscle repair. There were no post-operative complications at 3-month follow-up. CONCLUSIONS: In large MMCs with excess skin, the use of a deepithelialized skin flap can potentially be an alternative or adjunct to a muscle flap to buttress the dural repair. PMID- 27272949 TI - Kinship, maternal effects, and management: Juvenile mortality and survival in captive African painted dogs, Lycaon pictus. AB - In 77 African painted dog (Lycaon pictus) litters born in North American zoos since 1998, pup mortality at 30 days was 53% (n = 478). More alarmingly, 52% of those 77 litters had zero pups surviving at 30 days. Many variables may have the potential to affect pup mortality in captivity, including kinship, maternal age, prior maternal breeding experience, and numerous social and husbandry factors. Data on these variables were obtained from the North American Regional Studbook, with supplemental information compiled from a survey sent to painted dog breeding facilities in North America. Survival curve analysis revealed significant effects for maternal age and kinship, with kinship being most significant (chi2 , df = 19.71, 1; P < 0.0001). Pups born to unrelated parents had a median age at death two orders of magnitude higher than pups born to parents who were related to each other. Pup mortality was also lower for experienced mothers and for females under 2.5 years or between 4.5 and 6.5 years old. Follow-up analyses of these findings indicated that among first-time mothers, the youngest females achieved the lowest juvenile mortality, while juvenile mortality for experienced mothers was relatively low in all age classes until 6.5 years old. Regression analysis indicated that chances of survival are improved for pups born to younger mothers, unrelated parents, and in packs of >2 individuals. Enclosure size and area per animal may also be important factors. Our findings indicate that specific characteristics can be used to predict and potentially reduce pup mortality in captive African painted dogs. Zoo Biol. 35:367-377, 2016. (c) Wiley Periodicals, Inc. PMID- 27272948 TI - Extensive miRNA expression analysis in craniopharyngiomas. AB - PURPOSE: Craniopharyngiomas are benign tumors of the sellar or parasellar regions. They arise from the remnants of Rathke's pouch and are considered a "developmental disease." microRNAs are short non-coding RNAs that play a key regulatory role in the control of expression of entire gene networks. We performed an extensive analysis of miRNAs in craniopharyngiomas aiming to identify a miRNA expression signature that might aid in the prognosis of disease progression and outcome. METHODS: Thirty-seven craniopharyngioma samples from twenty-three patients, ten age-matched controls from autopsy, and ten infant controls from the developing pituitary from autopsy were evaluated for the expression of 754 miRNAs using TaqMan(r) Low Density Arrays (TLDAs) v2.0 (Applied Biosystems, Foster City, CA). RESULTS: Among the most differentially expressed miRNAs, downregulation of miR-132 appears to be a marker of aggressiveness and also plays a role in epithelial-mesenchymal transition. CONCLUSIONS: This is the first time that an extensive study of miRNA expression has been performed in craniopharyngiomas. Further research needs to be performed to investigate the potential role of miR-132 in the development and progression of craniopharyngiomas, and its value as a prognostic marker of aggressiveness. PMID- 27272951 TI - Disengaging from statistical significance. PMID- 27272952 TI - Biosynthesis of isoxazolin-5-one and 3-nitropropanoic acid containing glucosides in juvenile Chrysomelina. AB - Stable-isotope-labeled precursors were used to establish the biosynthetic pathway leading from beta-alanine towards isoxazolin-5-one glucoside 1 and its 3 nitropropanoate (3-NPA) ester 2 in Chrysomelina larvae. Both structural elements originate from sequestered plant-derived beta-alanine or from propanoyl-CoA that is derived from the degradation of some essential amino acids, e.g. valine. beta Alanine is converted into 3-NPA and isoxazolinone 5 by consecutive oxidations of the amino group of beta-Ala. Substituting the diphospho group of alpha-UDP glucose with 5 generates the isoxazolin-5-one glucoside 1, which serves in the circulating hemolymph of the larva as a platform for esterification with 3 nitropropanoyl-CoA. The pathway was validated with larvae of Phaedon cochleariae, Chrysomela populi as well as Gastrophysa viridula. PMID- 27272950 TI - Deep-sequencing transcriptome analysis of field-grown Medicago sativa L. crown buds acclimated to freezing stress. AB - Medicago sativa L. (alfalfa) 'Zhaodong' is an important forage legume that can safely survive in northern China where winter temperatures reach as low as -30 degrees C. Survival of alfalfa following freezing stress depends on the amount and revival ability of crown buds. In order to investigate the molecular mechanisms of frost tolerance in alfalfa, we used transcriptome sequencing technology and bioinformatics strategies to analyze crown buds of field-grown alfalfa during winter. We statistically identified a total of 5605 differentially expressed genes (DEGs) involved in freezing stress including 1900 upregulated and 3705 downregulated DEGs. We validated 36 candidate DEGs using qPCR to confirm the accuracy of the RNA-seq data. Unlike other recent studies, this study employed alfalfa plants grown in the natural environment. Our results indicate that not only the CBF orthologs but also membrane proteins, hormone signal transduction pathways, and ubiquitin-mediated proteolysis pathways indicate the presence of a special freezing adaptation mechanism in alfalfa. The antioxidant defense system may rapidly confer freezing tolerance to alfalfa. Importantly, biosynthesis of secondary metabolites and phenylalanine metabolism, which is of potential importance in coordinating freezing tolerance with growth and development, were downregulated in subzero temperatures. The adaptive mechanism for frost tolerance is a complex multigenic process that is not well understood. This systematic analysis provided an in-depth view of stress tolerance mechanisms in alfalfa. PMID- 27272953 TI - Plant invasion is associated with higher plant-soil nutrient concentrations in nutrient-poor environments. AB - Plant invasion is an emerging driver of global change worldwide. We aimed to disentangle its impacts on plant-soil nutrient concentrations. We conducted a meta-analysis of 215 peer-reviewed articles and 1233 observations. Invasive plant species had globally higher N and P concentrations in photosynthetic tissues but not in foliar litter, in comparison with their native competitors. Invasive plants were also associated with higher soil C and N stocks and N, P, and K availabilities. The differences in N and P concentrations in photosynthetic tissues and in soil total C and N, soil N, P, and K availabilities between invasive and native species decreased when the environment was richer in nutrient resources. The results thus suggested higher nutrient resorption efficiencies in invasive than in native species in nutrient-poor environments. There were differences in soil total N concentrations but not in total P concentrations, indicating that the differences associated to invasive plants were related with biological processes, not with geochemical processes. The results suggest that invasiveness is not only a driver of changes in ecosystem species composition but that it is also associated with significant changes in plant-soil elemental composition and stoichiometry. PMID- 27272954 TI - Synthesis of isoindolin-1-one derivatives via multicomponent reactions of methyl 2-formylbenzoate and intramolecular amidation. AB - Four series of heterocyclic compounds were obtained using Ugi-type multicomponent reactions (MCRs) with methyl 2-formylbenzoate as one of the starting materials. A facile and efficient one-pot procedure was suitable for all the MCRs under acidic conditions. This process provided access to four series of complex and potentially biologically active scaffolds. PMID- 27272955 TI - Whipple's disease without gastrointestinal symptoms: a challenging diagnosis. PMID- 27272957 TI - Introducing Technical Skills Assessment Into Certification: Closing the Implementation Gap. PMID- 27272956 TI - Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment: a prospective web-based multi-center study in multiple sclerosis patients with a relapse. AB - In a prospective multi-center observational study, we evaluated the frequency, severity, and impact on activities of daily living (ADL) of adverse effects (AEs) of high-dose intravenous methylprednisolone (IVMP) in relapsing remitting multiple sclerosis (MS) patients with a relapse. Online self-report questionnaires stating IVMP's most common AEs were completed at baseline, the 2nd day of treatment, and 1 day and 1 week after treatment. Eighty-five patients were included, 66 completed the baseline questionnaire, and 59 completed at least one post-baseline questionnaire. Patients reported on average 4 (median) AEs; two (3.4 %) reported no AE. Most frequent was change in taste (61 %), facial flushing (61 %), sick/stomach pain (53 %), sleep disturbance (44 %), appetite change (37 %), agitation (36 %), and behavioral changes (36 %). Of all AEs, 34.3 % were severe and 37.9 % impacted on ADL. A 3-day course resulted in 4 (median) AEs and a 5-day course in 7. All patients with high disease impact had two or more AEs, compared with 79 % of those with low impact (p < 0.01). Of patients with high disability, 45 % had severe AEs, compared with 16 % of those with low disability. Severe central nervous system (CNS)-related AEs occurred two times more frequently in patients with high disease impact, and two-and-a-half times more frequently in patients with high disability. Therefore, in virtually all patients, high-dose IVMP leads to AEs, with about one of three AEs being severe with impact on ADL. Patients with high disease impact or high disability may experience more (severe) AEs, due to a higher occurrence of severe CNS-related AEs. PMID- 27272958 TI - Reduced 30-Day Mortality After Laparoscopic Colorectal Cancer Surgery: A Population Based Study From the Dutch Surgical Colorectal Audit (DSCA). AB - OBJECTIVES: To evaluate the impact of a laparoscopic resection on postoperative mortality after colorectal cancer surgery. BACKGROUND: The question whether laparoscopic resection (LR) compared with open surgery [open resection (OR)] for colorectal cancer influences the risk of postoperative mortality remains unresolved. Several meta-analyses showed a trend but failed to reach statistical significance. The exclusion of high-risk patients and insufficient power might be responsible for that. We analyzed the influence of LR on postoperative mortality in a risk-stratified comparison and secondly, we studied the effect of LR on postoperative morbidity. METHODS: Data from the Dutch Surgical Colorectal Audit (2010-2013) were used. Homogenous subgroups of patients were defined on the basis of factors influencing the choice of surgical approach and risk factors for postoperative mortality. Crude mortality rates were compared between LR and OR. The influence of LR on postoperative complications was evaluated using both univariable and multivariable analyses. RESULTS: In patients undergoing elective surgery for nonlocally advanced, nonmetastasized colon cancer, LR was associated with a significant lower risk of postoperative mortality than OR in 20/22 subgroups. LR was independently associated with a lower risk of cardiac (odds ratio: 0.73, 95% confidence interval: 0.66-0.82) and respiratory (odds ratio: 0.73, 95% confidence interval: 0.64-0.84) complications. CONCLUSIONS: LR reduces the risk of postoperative mortality compared with OR in elective setting in patients with nonlocally advanced, nonmetastasized colorectal cancer. Especially elderly frail patients seem to benefit because of reduced cardiopulmonary complications. These findings support widespread implementation of LR for colorectal cancer also in patients at high operative risk. PMID- 27272959 TI - Deintensification of Routine Medical Services: The Next Frontier for Improving Care Quality. PMID- 27272960 TI - Commercial Milk Enzyme-Linked Immunosorbent Assay (ELISA) Kit Reactivities to Purified Milk Proteins and Milk-Derived Ingredients. AB - Numerous commercial enzyme-linked immunosorbent assay (ELISA) kits exist to quantitatively detect bovine milk residues in foods. Milk contains many proteins that can serve as ELISA targets including caseins (alpha-, beta-, or kappa casein) and whey proteins (alpha-lactalbumin or beta-lactoglobulin). Nine commercially-available milk ELISA kits were selected to compare the specificity and sensitivity with 5 purified milk proteins and 3 milk-derived ingredients. All of the milk kits were capable of quantifying nonfat dry milk (NFDM), but did not necessarily detect all individual protein fractions. While milk-derived ingredients were detected by the kits, their quantitation may be inaccurate due to the use of different calibrators, reference materials, and antibodies in kit development. The establishment of a standard reference material for the calibration of milk ELISA kits is increasingly important. The appropriate selection and understanding of milk ELISA kits for food analysis is critical to accurate quantification of milk residues and informed risk management decisions. PMID- 27272961 TI - Venous Thromboembolism in Children: Is It Preventable? AB - The incidence of venous thromboembolism (VTE) in children is increasing. Hospitalized infants and adolescents are at highest risk, and most individuals who have VTE have multiple thrombotic risk factors. The presence of a central venous catheter (CVC) is the most frequent risk factor for childhood thrombosis. Childhood VTE has significant consequences in relation to the thrombotic event and the anticoagulant therapy used for its treatment. Identification of the most prevalent risk factors for VTE, particularly among adolescents, has moved the focus toward prevention of thrombosis. Risk assessment models have been developed to identify individuals who are at higher risk with a view to employing preventative strategies such as mechanical and chemical thromboprophylaxis (TP). There is currently little evidence to support the efficacy of such strategies for preventing either CVC-associated thrombosis or thrombosis at other sites. In addition, there are concerns about adverse consequences of mechanical and chemical TP in a population where the overall incidence of VTE remains low. PMID- 27272962 TI - Factor VIII Activity and Inhibitor Assays in the Diagnosis and Treatment of Hemophilia A. AB - The treatment of a patient with a factor VIII (FVIII) deficiency can be complicated. The mainstay of therapy is factor replacement. Replacement therapy can be given prophylactically, with the goal of decreasing hemarthroses and spontaneous hemorrhage, or on-demand for the bleeding patient. Intra- and interindividual variability in a patient's response to treatment has been well documented by the differences in observed half-lives of infused product. Although weight-based dosing nomograms are most often used, personalized therapies are coming into use to ease the burden of therapy and cost. The most significant complication of treatment is the formation of inhibitors to FVIII. The role of the laboratory is to provide results for FVIII activity that accurately reflects a patient's baseline level and response to treatment. However, factor activity assays have many components that can contribute to result variability. These include the methodology and reagent components used to measure the FVIII activity, the reference standard employed, algorithm used to interpret the dilutions, and the replacement factor being measured. An understanding of assay variables and their impact will assist in providing accurate factor activity results and appropriate patient care. PMID- 27272963 TI - Assessing Safety of Thrombolytic Therapy. AB - Thrombolytic therapy involves thrombolytic agents administered to patients suffering from venous or arterial thrombosis. The therapy induces systemic effects interrelated with the thrombolytic agent used. Bleeding is a prominent complication of thrombolytic therapy. Exhaustion of coagulation factors, generation of excessive amounts of fibrin degradation products (FDPs), therapy induced activation of coagulation, therapy-induced anticoagulation, and formation of new fibrin all illustrate the complexity of effects of the treatment and challenges the hemostatic balance in the patients. The therapy-induced effects can be modulated by parallel administration of anticoagulants. Risk assessment is mandatory prior to thrombolytic therapy. Anticoagulated and unconscious patients represent particular safety concerns, and should be fully evaluated. Several guidelines describe the choice of tests and their safety limits in relation to pretreatment evaluation of anticoagulated patients. Fibrinogen depletion and FDPs during treatment may be promising markers for the evaluation of bleeding risk posttreatment. Future risk assessment measures should focus on the dynamics of the hemostatic balance. Here, thromboelastography may be considered a tool addressing clot formation, fibrin structure, and fibrinolytic resistance in parallel. Suitable laboratory analysis performed shortly after treatment may help to recognize severe treatment-induced systemic effects that can be counteracted by rational treatment, thereby reducing bleeding risk. PMID- 27272964 TI - Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations. AB - When administering unfractionated heparin (UFH), therapeutic levels of anticoagulation must be achieved rapidly and maintained consistently in the therapeutic range. The basic assays for monitoring UFH therapy are the activated partial thromboplastin time (APTT) and/or the chromogenic antifactor Xa or antithrombin assays. For many laboratories, the APTT is the preferred standard of practice; however, the APTT is a surrogate marker that only estimates the heparin concentration. Many factors, including patient variation, reagents of the APTT, UFH composition, and concentration can influence the APTT result. This article reviews various methods to determine the heparin therapeutic range and presents recommendations for the laboratory to establish an APTT heparin therapeutic range for all sizes of hospitals. PMID- 27272965 TI - Thrombosis in Autoimmune Diseases: A Role for Immunosuppressive Treatments? AB - Autoimmune diseases are not infrequently associated with arterial or venous thrombotic events. Chronic inflammation and immune system impairment are considered the main pathogenetic mechanisms. Some of the drugs used in the treatment of such diseases have been associated with an increased risk of thrombosis. On the contrary, their anti-inflammatory and immune modulator activity could correct some mechanisms leading to thrombosis. In this review, recent evidence available on this topic is examined. There is a lack of adequate studies, but available evidence suggests that glucocorticoids and high-dose immunoglobulins are associated with an increased incidence of venous thromboembolism. Although available data do not allow drawing definite conclusions and more data are needed from future studies and registries, physicians should be aware of these associations. PMID- 27272966 TI - Risk Factors for Cerebral Venous Thrombosis. AB - Cerebral venous thrombosis (CVT) is a rare thrombotic disorder involving the cerebral veins and dural sinuses. In contrast to more common sites of venous thromboembolism (VTE), such as the legs and lungs, CVT mainly affects young adults and children, and women are affected three times more often than men. Although presenting symptoms are variable, headache is usually the first symptom, often in combination with focal neurologic deficits and epileptic seizures. The primary therapy for CVT consists of heparin followed by oral anticoagulation for at least 3 to 6 months. The mortality in the acute phase is 5 to 10% and a substantial proportion of survivors suffer from long-term disabilities. A large number of risk factors have been linked to CVT, although the scientific evidence for an association varies considerably between risk factors. Some risk factors, such as hereditary thrombophilia, correspond with risk factors for more common sites of VTE, whereas others, such as head trauma, are specific to CVT. In most patients, at least one risk factor can be identified. In this review, we provide an overview of the risk factors for CVT. PMID- 27272967 TI - Clinical Outcomes of Venous Thromboembolism in Patients with and without Cancer: The SWIss Venous ThromboEmbolism Registry (SWIVTER). AB - Background The association between cancer and venous thromboembolism (VTE) in producing adverse clinical outcomes requires further investigation. Methods In the Swiss Venous ThromboEmbolism Registry (SWIVTER), we compared adverse clinical outcomes between 493 patients with cancer-associated VTE and 1,569 VTE patients without cancer, and identified independent predictors of 90-day mortality. Results Among cancer patients, 351 (71%) had active disease at the time of VTE diagnosis and 232 (47%) had metastatic disease. Cancer patients more frequently had asymptomatic VTE (13 vs. 4%; p < 0.001), iliofemoral deep vein thrombosis (42 vs. 32%; p = 0.017), and upper extremity deep vein thrombosis (16 vs. 7%; p < 0.001). Cancer was associated with an increased risk of cumulative 90-day mortality (13.0 vs. 2.2%; hazard ratio [HR], 6.27; 95% confidence interval [CI], 4.13-9.50; p < 0.001), recurrent VTE (4.7 vs. 2.3%; HR, 2.05; 95% CI, 1.21-3.45; p = 0.007), and bleeding requiring medical attention (5.7 vs. 3.3%; HR, 1.80; 95% CI, 1.13-2.86; p = 0.013). Among cancer patients, the strongest factor associated with mortality was metastatic disease (HR, 4.86; 95% CI, 2.68-8.81; p < 0.001), whereas it was pulmonary embolism among noncancer patients (HR, 4.96; 95% CI, 1.50-16.45; p = 0.009). Symptomatic as compared with asymptomatic VTE predicted neither mortality (12.6 vs. 15.9%; HR, 0.76; 95% CI, 0.39-1.49; p = 0.42) nor recurrent VTE (4.7 vs. 4.8%; HR, 0.98; 95% CI, 0.29-3.31; p = 0.98) in cancer patients. Conclusion In SWIVTER, early mortality of cancer-associated VTE was mainly driven by the extent of cancer disease and not by VTE symptoms or severity. PMID- 27272968 TI - Monitoring of Hemostasis and Management of Anticoagulant Thromboprophylaxis in Pregnant Women with Increased Risk of Fetal Loss. AB - Physiological prothrombotic changes during pregnancy and the postpartum period, along with other preexisting maternal risk factors, increase the risk of both venous thromboembolism (VTE) and adverse pregnancy outcomes. Pregnancy complications that develop due to placental insufficiency as a result of inappropriate activation of coagulation are present in more than 5% of pregnancies and can contribute to significant maternal morbidity and mortality. Therefore, anticoagulant prophylaxis in women with congenital and acquired thrombophilic conditions should be actively considered. According to the Guidelines of American College of Chest Physicians, the use of low-molecular weight heparin is suggested for prophylaxis of VTE and pregnancy complications in high-risk pregnant women. However, personalized refinements of such thromboprophylaxis remains unspecified, despite the necessity of better targeted recommendations for life-threatening conditions. We, therefore, review the possibilities of longitudinal monitoring and comprehensive assessment of changes in hemostasis in the group of high-risk pregnant women, which can then be used for early prediction and individualization of the optimal anticoagulant thromboprophylaxis of pregnancy complications. Simultaneously, we present our single-center experience with such monitoring and our first series of results. PMID- 27272969 TI - Influence of dietary slow-release urea on growth performance, organ development and serum biochemical parameters of mutton sheep. AB - Eighty Dorper * thin-tailed Han cross-bred non-castrated male lambs [mean body weight (BW), 25.87 +/- 1.06 kg] were randomly allocated to one of five different concentrations of slow-release urea (urea phosphate, UP). The feed consisted of an equal amount of concentrate diet and roughage; the concentrate feed was formulated to be isoenergetic and isonitrogenic and contained 0%, 1%, 2%, 4% and 8% UP (UP0.0, UP1.0, UP2.0, UP4.0 and UP8.0, respectively) as a replacement for soya bean meal. Feed intake, BW, average daily gain (ADG), feed utilisation efficiency (FUE), absolute and relative organ weights and biochemical and histopathological parameters were measured. Feed intake, BW, ADG and FUE significantly decreased in the group receiving UP8.0 (p < 0.05), but no difference was found among the other groups (p > 0.05). Quadratic equations were developed between the UP dosage in the concentrate feed and ADG or FUE (r2 = 0.973 for ADG and r2 = 0.761 for FUE) to determine the appropriate dosage of UP given the desire to maximise either ADG or FUE, the appropriate dosage (feed concentration) was calculated as 2.01% UP to achieve the greatest ADG or 2.13% UP to achieve the best FUE. The relative weight of the liver (% BW) in the UP2.0 groups was significantly greater than that of UP0.0 (p < 0.05), and the relative weight of the intestine in the UP8.0 was significantly greater than that of UP0.0 (p < 0.05); the relative weight of the carcass, heart, spleen, lung, kidney, rumen, reticulum, omasum and abomasum did not differ among treatments (p > 0.05). The UP8.0 treatment significantly increased serum phosphorus levels (p < 0.05) and decreased the levels of alkaline phosphatase, glucose and calcium (Ca) compared with the lower UP dosage (p < 0.05). No histopathological differences were found in either hepatic tissues or renal tissues among treatments. Dietary UP as a replacement for soya bean in concentrate feeds for mutton sheep should not exceed 4%, as higher dosing may cause malnutrition and mineral disorders. PMID- 27272970 TI - Anticipatory Electrodermal Response as a Differentiating Somatic Marker Between Children with ADHD and Controls. AB - Six children with Attention Deficit Hyperactivity Disorder (ADHD) and five control children between the ages of 9 and 11 years were administered an adapted version of the Iowa Gambling Task while measuring anticipatory electrodermal response (EDR). Anticipatory EDR measures were compared between groups. Results indicate that the ADHD group exhibited significantly lower autonomic reactivity to anticipated consequences, evidencing a neuropsychological profile similar to patients with lesions in the ventromedial prefrontal cortex. PMID- 27272972 TI - HHV-6 and seizure: A systematic review and meta-analysis. AB - Human herpesvirus-6 (HHV-6) is a common infection in childhood. This systematic review aims to assess the relationship between HHV-6 infection and seizure disorders based on available literature. MEDLINE database was searched using a search strategy. We included studies that were published after 1993 in English, and described patients with HHV-6 infection and accompanying seizure or status epilepticus. We identified 503 articles, and included 147 studies. Meta-analysis results showed a 0.21 detection rate of HHV-6 in febrile seizure patients. In the febrile seizure group (110 cases), 76 patients had simple and 34 had complex febrile seizures. Patients with "HHV-6 infection and status epilepticus" had a mean age of 16.24 months. In children with febrile illnesses, a higher index of clinical suspicion for HHV-6 infection may be required. Further studies including CSF and brain tissue may be needed to validate relationships between HHV6 infection and epilepsy. J. Med. Virol. 89:161-169, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27272973 TI - Perioperative risk factors for impaired neurodevelopment after cardiac surgery in early infancy. AB - OBJECTIVE: Historical cohort studies have reported adverse neurodevelopment following cardiac surgery during early infancy. Advances in surgical techniques and perioperative care have coincided with updating of neurodevelopmental assessment tools. We aimed to determine perioperative risk factors for impaired neurodevelopment at 2 years following surgery for congenital heart disease (CHD) in early infancy. DESIGN AND PATIENTS: We undertook a prospective longitudinal study of 153 full-term infants undergoing surgery for CHD before 2 months of age. Infants were excluded if they had a genetic syndrome associated with neurodevelopmental impairment. OUTCOME MEASURES: Predefined perioperative parameters were recorded and infants were classified according to cardiac anatomy. At 2 years, survivors were assessed using the Bayley Scales of Infant Development-III. RESULTS: At 2 years, 130 children (98% of survivors) were assessed. Mean cognitive, language and motor scores were 93.4+/-13.6, 93.6+/-16.1 and 96.8+/-12.5 respectively (100+/-15 norm). Twenty (13%) died and 12 (9%) survivors had severe impairment (score <70), mostly language (8%). The lowest scores were in infants born with single ventricle physiology with obstruction to the pulmonary circulation who required a neonatal systemic-to-pulmonary artery shunt. Additional risk factors for impairment included reduced gestational age, postoperative elevation of lactate or S100B and repeat cardiac surgery. CONCLUSIONS: In the modern era of infant cardiac surgery and perioperative care, children continue to demonstrate neurodevelopmental delays. The use of updated assessment tools has revealed early language dysfunction and relative sparing of motor function. Ongoing follow-up is critical in this high-risk population. PMID- 27272971 TI - Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice. AB - The mitochondria-associated membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) which acts as an intracellular signaling hub. MAM dysfunction has been related to liver disease. We report a high-throughput mass spectrometry-based proteomics characterization of MAMs from mouse liver, which portrays them as an extremely complex compartment involved in different metabolic processes, including steroid metabolism. Interestingly, we identified caveolin-1 (CAV1) as an integral component of hepatic MAMs, which determine the relative cholesterol content of these ER subdomains. Finally, a detailed comparative proteomics analysis between MAMs from wild type and CAV1-deficient mice suggests that functional CAV1 contributes to the recruitment and regulation of intracellular steroid and lipoprotein metabolism-related processes accrued at MAMs. The potential impact of these novel aspects of CAV1 biology on global cell homeostasis and disease is discussed. PMID- 27272974 TI - Vitamin A toxicity presenting as bone pain. AB - A 4-year-old boy presented with severe bone pains, refusal to walk, diffuse bony swelling of forelimbs, skin changes and abdominal pain, with symptoms evolving over 6 weeks. Blood screening tests were normal except for raised aspartate aminotransferase (AST). Radiographs revealed thickened periosteum, widening of the diaphyses of long bones and lifted periosteum in mid-shaft of ulnae and right femur. Skeletal scintigraphy showed a high uptake of radionuclide at clinically affected and unaffected sites, suggestive of multifocal osteoblastic skeletal lesions. After repeated enquiries, his parents admitted to giving him massive doses of preformed vitamin A for over 3 months as 'health tablets'. Surprisingly, he did not have overt liver disease typically found with much smaller doses, although the dermal changes and musculoskeletal pathology were florid. He made a full clinical recovery within 2 months of cessation of vitamin A. PMID- 27272975 TI - Design, Synthesis, and Functionalization of Imidazoheterocycles. AB - Over the years, various strategies have been reported for the synthesis of imidazo[1,2-a]pyridines due to their importance in different fields. In this account, we represent the methods developed by our group for the synthesis and functionalization of imidazo[1,2-a]pyridines. Different synthetic strategies have been developed using easily accessible reactants for this purpose. We envisage that these newly developed protocols will be very useful for the synthesis of functionalized molecules bearing imidazo[1,2-a]pyridine scaffolds. These strategies will also be attractive for the construction of other pharmaceutically important heterocycles. PMID- 27272976 TI - Continuous dopaminergic stimulation therapy for Parkinson's disease - recent advances. AB - PURPOSE OF REVIEW: We aim to review the most interesting recent advances on the clinical aspects of continuous dopaminergic stimulation in Parkinson's disease. RECENT FINDINGS: Several large, open-label studies have presented data that are in line with the randomized controlled trial on L-dopa-carbidopa intestinal gel infusion, which shows that a continuous drug delivery can improve motor fluctuations and dyskinesia in patients with advanced Parkinson's disease. Furthermore, new extended-release formulations of L-dopa aim to stabilize plasma concentrations and thus reduce the degree of motor complications - despite a reduced number of daily doses. Transdermal rotigotine has been shown to be effective for specific subgroups of patients, although the general effect on nonmotor symptoms is still unclear. New products for L-dopa infusion are also at different stages of development, but the routes of administration are widely different: intrajejunal, subcutaneous, and oral. SUMMARY: The understanding of the mechanisms behind the complications of long-term L-dopa treatment is still not complete, but therapies aiming for continuous dopaminergic stimulation are already widely used in clinical practice and the evidence strength is improving. However, there is still an urgent need for both less invasive and less costly options in order to increase access to these therapies. PMID- 27272977 TI - Atypical parkinsonism - new advances. AB - PURPOSE OF REVIEW: This update discusses novel aspects on genetics, pathophysiology and therapeutic approaches for atypical parkinsonism (progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy) published in the last 2 years. RECENT FINDINGS: In terms of genetics, in progressive supranuclear palsy and corticobasal degeneration new risk loci have been identified but also their possible association to disease pathogenesis. In multiple system atrophy, there is still a debate as to whether COQ2 variants are associated with disease, at least in non-Asian population, whereas at the same time evidence of coenzyme Q10 deficiency in serum and brains of MSA patients has been reported. In terms of pathogenesis, the 'prion' hypothesis has prevailed in the last years in the literature, and the first clinical studies based on such disease mechanisms are already in phase I. Despite all these discoveries, clinical diagnosis still remains poor, and phenotypic variability is reported much higher than previously thought. A plethora of studies testing possible neuroprotective agents are currently ongoing. SUMMARY: The knowledge on all aspects of atypical parkinsonism has increased tremendously in the last 2 years, leading the field closer to the understanding of the pathophysiology of these diseases, and to the discovery of a neuroprotective treatment. PMID- 27272979 TI - An evaluation of invasive fungal sinusitis outcomes with subsite analysis and use of frozen section analysis. AB - BACKGROUND: Invasive fungal sinusitis (IFS) is an aggressive mycosis of the nasal cavity with frequent extension to adjacent structures. Occurring more commonly in immunocompromised individuals, prognosis is typically poor despite aggressive treatment. This study aims to examine postoperative outcomes and survival of a cohort of fungal sinusitis patients at an academic center, as well as identify causes of death in IFS patients. METHODS: This study was a retrospective chart review of patient charts and departmental records, yielding patient demographics, medical and surgical treatments, pathology records, and outcomes data. RESULTS: Twenty-seven patients were identified from departmental records between 1998 and 2014. Twenty-one patients presented with Mucor infections, whereas the remaining 6 patients had Aspergillus. All patients were immunocompromised: diabetes (n = 14) and hematologic malignancy (n = 13). Three patients had multiple causes of immunosuppression. Most commonly involved subsites were the maxillary, ethmoid, and sphenoid sinuses. Nasal septum involvement was independently associated with mortality (p < 0.01). Overall mortality was 57.7% within 1 year, although 66.7% of fatalities occurred within 1 month of diagnosis. CONCLUSION: Overall survival for IFS remains poor. Widespread disease and nasal septum involvement were associated with a negative clinical course. Early identification and aggressive surgical and antifungal therapy is warranted. Even despite intense therapy, comorbid conditions and drug toxicity increase mortality and complicate the clinical course. PMID- 27272978 TI - Highly efficient residue-selective labeling with isotope-labeled Ile, Leu, and Val using a new auxotrophic E. coli strain. AB - We recently developed a practical protocol for preparing proteins bearing stereo selectively (13)C-methyl labeled leucines and valines, instead of the commonly used (13)C-methyl labeled precursors for these amino acids, by E. coli cellular expression. Using this protocol, proteins with any combinations of isotope labeled or unlabeled Leu and Val residues were prepared, including some that could not be prepared by the precursor methods. However, there is still room for improvement in the labeling efficiencies for Val residues, using the methods with labeled precursors or Val itself. This is due to the fact that the biosynthesis of Val could not be sufficiently suppressed, even by the addition of large amounts of Val or its precursors. In this study, we completely solved this problem by using a mutant strain derived from E. coli BL21(DE3), in which the metabolic pathways depending on two enzymes, dihydroxy acid dehydratase and beta isopropylmalate dehydrogenase, are completely aborted by deleting the ilvD and leuB genes, which respectively encode these enzymes. The DeltailvD E. coli mutant terminates the conversion from alpha,beta-dihydroxyisovalerate to alpha ketoisovalerate, and the conversion from alpha,beta-dihydroxy-alpha methylvalerate to alpha-keto-beta-methylvalerate, which produce the preceding precursors for Val and Ile, respectively. By the further deletion of the leuB gene, the conversion from Val to Leu was also fully terminated. Taking advantage of the double-deletion mutant, DeltailvDDeltaleuB E. coli BL21(DE3), an efficient and residue-selective labeling method with various isotope-labeled Ile, Leu, and Val residues was established. PMID- 27272980 TI - Efficacy of electrochemotherapy for eruptive legs keratoacanthomas. AB - Generalized eruptive keratoacanthoma, is considered a serious condition because the eruptions are diffuse, persistent, and recurrent. Constant pruritus, visceral neoplasms, and unsatisfactory response to treatment are ominous prognostic factors. Even if skin cancers are usually well controlled with surgical and/or radiotherapic approaches, there are some cases in which these two techniques are not effective. With respect to surgery, radiotherapy and other standard treatments, ECT acts rapidly on multiple lesions with limited side effects and no functional impairment; moreover, repeated sessions can be performed to achieve or maintain the clinical response. We report a case of generalized eruptive keratoacanthomas in which electrochemotherapy was effective in inducing local regression of skin lesions. A 72-year-old woman with eruptive and painful keratoacanthomas for 3 months on both the lower limbs in which the conventional treatments could not be cosmetically acceptable. One session of electrochemotherapy with bleomycin sulfate was then performed on all isolated skin lesions. The treatment was well tolerated and led to a rapid clinical regression of the treated lesions. Use of ECT should be considered as an excellent alternative to current therapies in treatment of painful eruptive keratoacanthomas with a significant improvement of quality of life. PMID- 27272981 TI - Primary stenting for TASC C and D femoropopliteal lesions: one-year results from a multicentric trial on 203 patients. AB - BACKGROUND: Recent advances in endovascular techniques have made it a seductive choice in the management of TASC C and D lesions. Currently, this tendency remains controversial, despite high success rates. The aim of the study was to regroup and harmonize the results of three surgical teams in 5 centers in order to obtain the largest series ever published on TASC C and D femoro-popliteal lesions primary stenting. METHODS: Two hundred and three patients and 209 lower limbs were included from March 2008 to October 2013. Each patient underwent primary stenting for TASC C or D femoro-popliteal lesions. RESULTS: Mean age was 70+/-10; 71.4% were male with a 39.8% rate of coronary heart disease, 20.1% of renal insufficiency and 35.9% of diabetes; 57,4% suffered from claudication and 42.6% from critical limb ischemia (CLI); 61.8% of the 144 limbs analyzed for run off presented with 3 patent infra-popliteal arteries. Four hundred and three stents were implanted in the 209 limbs included. Median stented length was 252 mm. Associated procedures were performed in 35 patients (17.0%) including 4.3% minor amputations. The 30-day mortality rate was 1.4% (3 patients). Major complications occurred in 19 patients (9.3%) including 7 patients (3.4%) presented with early in-stent thrombosis. Median follow-up duration was 12 months (range 9.5-17.2 months). The 12-month mortality rate was 11.8% (24 patients). The 3, 6 and 12 months primary patency rates according to Kaplan Meier estimates were 98.1+/-0.9, 85.2+/-2.5 and 67.0+/-3.3% respectively. Secondary patency rates were 96.1+/-1.9, 89.3+/-3.0 and 75.7+/-4.2% respectively. A subgroup analysis reported significantly higher patency rates for TASC C lesions compared to TASC D lesions (82.1% vs. 44% respectively, P=0.009). The 12-month in-stent thrombosis and restenosis rates were 19.6% and 13.9% respectively. A subgroup analysis showed higher rates of in-stent restenosis for TASC D lesions compared to TASC C lesions (35% vs. 10% respectively, P=0.005). The stent fracture rate was equal to 10.2% (30 stents). Occurrence of in-stent thrombosis and restenosis were associated with 3 and 5 cases of stent fracture (type II to IV) respectively. Freedom from TLR was 70.5%. Rutherford class decreased from 3.7 to 0.9 (3.52+/-1.06 to 0.75+/ 1.24) (P<0.0001). At 12 months 61.3% were asymptomatic, 33.3% suffered from claudication (21.3% Rutherford 1) and 5.4% suffered from CLI. Healing rates were 63.9% with a limb salvage rate of 95.5% and a major amputation rate of 3.8%. CONCLUSIONS: This is the largest series of TASC C and D femoro-popliteal lesions primary stenting to our knowledge. The results are encouraging with acceptable primary patency and clinical improvement at 12 months. Results from mid- to long term follow-up are awaited. PMID- 27272983 TI - Organocatalytic asymmetric Michael addition of alpha-alkylidene succinimides to nitrostyrenes. AB - A bifunctional squaramide-catalyzed asymmetric Michael addition reaction of alpha alkylidene succinimides with nitrostyrenes and a nitrodiene has been developed. This organocatalytic asymmetric reaction provides easy access to functionalized succinimides with two contiguous stereocenters with a broad substrate scope. The desired succinimide derivatives were obtained in good to excellent yields (up to 98%) with high to excellent diastereoselectivities (up to >99 : 1 dr) and excellent enantioselectivities (up to 99% ee). This protocol provides a straightforward entry to functionalized chiral succinimide derivatives from simple starting materials. PMID- 27272982 TI - Impact testing of the residual limb: System response to changes in prosthetic stiffness. AB - Currently, it is unknown whether changing prosthetic limb stiffness affects the total limb stiffness and influences the shock absorption of an individual with transtibial amputation. The hypotheses tested within this study are that a decrease in longitudinal prosthetic stiffness will produce (1) a reduced total limb stiffness, and (2) reduced magnitude of peak impact forces and increased time delay to peak force. Fourteen subjects with a transtibial amputation participated in this study. Prosthetic stiffness was modified by means of a shock absorbing pylon that provides reduced longitudinal stiffness through compression of a helical spring within the pylon. A sudden loading evaluation device was built to examine changes in limb loading mechanics during a sudden impact event. No significant change was found in the peak force magnitude or timing of the peak force between prosthetic limb stiffness conditions. Total limb stiffness estimates ranged from 14.9 to 17.9 kN/m but were not significantly different between conditions. Thus, the prosthetic-side total limb stiffness was unaffected by changes in prosthetic limb stiffness. The insensitivity of the total limb stiffness to prosthetic stiffness may be explained by the mechanical characteristics (i.e., stiffness and damping) of the anatomical tissue within the residual limb. PMID- 27272984 TI - Polymer Morphological Change Induced by Terahertz Irradiation. AB - As terahertz (THz) frequencies correspond to those of the intermolecular vibrational modes in a polymer, intense THz wave irradiation affects the macromolecular polymorph, which determines the polymer properties and functions. THz photon energy is quite low compared to the covalent bond energy; therefore, conformational changes can be induced "softly," without damaging the chemical structures. Here, we irradiate a poly(3-hydroxybutylate) (PHB) / chloroform solution during solvent casting crystallization using a THz wave generated by a free electron laser (FEL). Morphological observation shows the formation of micrometer-sized crystals in response to the THz wave irradiation. Further, a 10 20% increase in crystallinity is observed through analysis of the infrared (IR) absorption spectra. The peak power density of the irradiating THz wave is 40 MW/cm(2), which is significantly lower than the typical laser intensities used for material manipulation. We demonstrate for the first time that the THz wave effectively induces the intermolecular rearrangement of polymer macromolecules. PMID- 27272986 TI - Application of infiltrated LSCM-GDC oxide anode in direct carbon/coal fuel cells. AB - Hybrid direct carbon/coal fuel cells (HDCFCs) utilise an anode based upon a molten carbonate salt with an oxide conducting solid electrolyte for direct carbon/coal conversion. They can be fuelled by a wide range of carbon sources, and offer higher potential chemical to electrical energy conversion efficiency and have the potential to decrease CO2 emissions compared to coal-fired power plants. In this study, the application of (La, Sr)(Cr, Mn)O3 (LSCM) and (Gd, Ce)O2 (GDC) oxide anodes was explored in a HDCFC system running with two different carbon fuels, an organic xerogel and a raw bituminous coal. The electrochemical performance of the HDCFC based on a 1-2 mm thick 8 mol% yttria stabilised zirconia (YSZ) electrolyte and the GDC-LSCM anode fabricated by wet impregnation procedures was characterized and discussed. The infiltrated oxide anode showed a significantly higher performance than the conventional Ni-YSZ anode, without suffering from impurity formation under HDCFC operation conditions. Total polarisation resistance (Rp) reached 0.8-0.9 Omega cm(2) from DCFC with an oxide anode on xerogel and bituminous coal at 750 degrees C, with open circuit voltage (OCV) values in the range 1.1-1.2 V on both carbon forms. These indicated the potential application of LSCM-GDC oxide anode in HDCFCs. The chemical compatibility of LSCM/GDC with carbon/carbonate investigation revealed the emergence of an A2BO4 type oxide in place of an ABO3 perovskite structure in the LSCM in a reducing environment, due to Li attack as a result of intimate contact between the LSCM and Li2CO3, with GDC being stable under identical conditions. Such reaction between LSCM and Li2CO3 was not observed on a LSCM-YSZ pellet treated with Li-K carbonate in 5% H2/Ar at 700 degrees C, nor on a GDC LSCM anode after HDCFC operation. The HDCFC durability tests of GDC-LSCM oxide on a xerogel and on raw bituminous coal were performed under potentiostatic operation at 0.7 V at 750 degrees C. The degradation mechanisms were addressed, especially on raw coal. PMID- 27272985 TI - Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis. AB - Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development of rheumatoid arthritis in Asian and European populations. Ancestry-related association heterogeneity was examined using Cochran's homogeneity tests for the disease association data from large Asian (n = 14,465; 9,299 discovery subjects and 5,166 validation subjects; 4 collections) and European (n = 45,790; 11 collections) rheumatoid arthritis case-control cohorts with Immunochip and genome wide SNP array data. We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I locus (PHeterogeneity = 9.6 * 10( 9) at rs73366469) and showed that this heterogeneity was due to an Asian-specific association effect (ORMeta = 1.37 and PMeta = 4.2 * 10(-13) in Asians; ORMeta = 1.00 and PMeta = 1.00 in Europeans). Trans-ancestral comparison and bioinfomatics analysis revealed a plausibly causal or disease-variant-tagging SNP (rs117026326; in linkage disequilibrium with rs73366469), whose minor allele is common in Asians but rare in Europeans. In conclusion, we identified largest-ever effect on Asian rheumatoid arthritis across human non-HLA regions at GTF2I by heterogeneity mapping followed by replication studies, and pinpointed a possible causal variant. PMID- 27272987 TI - Action Effects and Task Knowledge: The Influence of Anticipatory Priming on the Identification of Task-Related Stimuli in Experts. AB - The purpose of the present study was to examine the extent to which anticipation of an action's perceptual effect primes identification of task-related stimuli. Specifically, skilled (n = 16) and novice (n = 24) tennis players performed a choice-reaction time (CRT) test in which they identified whether the presented stimulus was a picture of a baseball bat or tennis racket. Following their response, auditory feedback associated with either baseball or tennis was presented. The CRT test was performed in blocks in which participants predictably received the baseball sound or tennis sound irrespective of which stimulus picture was displayed. Results indicated that skilled tennis players responded quicker to tennis stimuli when the response was predictably followed by the tennis auditory effect compared to the baseball auditory effect. These findings imply that, within an individual's area of expertise, domain-relevant knowledge is primed by anticipation of an action's perceptual effect, thus allowing the cognitive system to more quickly identify environmental information. This finding provides a more complete picture of the influence that anticipation can have on the cognitive-motor system. No differences existed for novices. PMID- 27272988 TI - Recovery Oriented Systems of Care (ROSC) and Recovery Management. PMID- 27272990 TI - Clinical Management of the Breast-Feeding Mother-Infant Dyad in Recovery From Opioid Dependence. AB - Human milk is one of the most health-promoting and cost-effective nutritional substances known to humankind. Breastmilk provides substantial and remarkable physiological and psychological health benefits. Within the last decade, there has been a resurgence of breast-feeding in the United States and worldwide and an increased awareness of the immense health benefits for mothers, infants, and societies that support it. Each mother-baby dyad is a unique pair, with distinct relationships, biases, barriers, and obstacles. This article aims to address clinical management for the opioid-recovering breast-feeding dyad and to translate current evidenced-based practice findings, recommendations, and resources to best support this unique population. The recovering breast-feeding mother and newborn with opioid dependence deserve special consideration and expert care to foster their recovery and breast-feeding efforts. It is our moral and ethical responsibility as healthcare professionals to enable, foster, and promote breast-feeding among all families, especially those who stand to benefit the greatest. Substance recovery cannot be treated in isolation, nor can breast feeding efforts; an interdisciplinary professional team effort promises the greatest chances for recovery success. With appropriate evidence-based practice support, training, and intervention by knowledgeable professionals, many women can overcome the biases and obstacles associated with opioid recovery to successfully breast-feed their babies. PMID- 27272989 TI - Recovery and Recovery-Oriented Systems of Care: Integrating Treatment for Substance Use, Primary Care, and Psychiatric-Mental Health Disorders. PMID- 27272991 TI - Part 1: The Theoretical Basis for Recovery-Oriented Management of Substance Use Disorders in Primary Care. AB - There is strong evidence in the literature that screening and brief counseling interventions are effective in detecting alcohol problems and decreasing alcohol consumption among patients in primary care settings but somewhat weaker evidence regarding screening and brief intervention for drug problems. In 2014, two published studies made news and caused concern among proponents of substance Screening, Brief Intervention and Referral to Treatment (SBIRT) programs, when their authors concluded that brief interventions were not effective for decreasing drug use among primary care patients identified through screening, and advised that widespread adoption of screening and brief intervention for drug use was not warranted.An evaluation of the theoretical foundations for evidence-based SBIRT services was conducted to produce possible explanations for why traditional SBIRT works well for individuals with unhealthy alcohol use but not as well for those with more serious substance use disorders, including drug use and alcohol/drug dependence. Smith and Liehr's evaluation framework for middle-range theory was utilized to analyze the Chronic Care Model, which was featured prominently in early SBIRT literature, and the newer Recovery Management model, which provides a philosophical framework for organizing modern addictions services and quality-of-life enhancements (Part 1 of this two-part series).Programs are more likely to succeed if guided by theory, and examination of relevant components of theory-based interventions can be useful in developing practical strategies for meeting program objectives. A new, theory-based, recovery-oriented framework for primary care SBIRT is introduced in Part 2 ("SBIRT+RM(C): A Proposed Model for Recovery-Oriented Primary Care"). PMID- 27272992 TI - Part 2: Screening, Brief Intervention and Referral to Treatment Plus Recovery Management: A Proposed Model for Recovery-Oriented Primary Care. AB - Part 1 of this two-part series (The Theoretical Basis for Recovery-Oriented Management of Substance Use Disorders in the Primary Care) explored the theoretical foundations for evidence-based substance Screening, Brief Intervention and Referral to Treatment (SBIRT) services. The aim was to produce possible explanations for why traditional SBIRT works well for individuals with unhealthy alcohol use but not as well for individuals who have more serious substance use disorders, including drug use and alcohol/drug dependence. Building on that analysis, through meaningful application of recovery management (RM) concepts within an integrated primary care/behavioral health context, a new, theory-based, recovery-oriented framework for primary care SBIRT is now introduced in Part 2. The proposed SBIRT Plus Recovery Management (SBIRT + RM) model moves traditional SBIRT from its original, limited, and narrow focus only on substance detection, brief intervention, and referral to its rightful, structured placement within a comprehensive, multidimensional, recovery-oriented system of care clinical practice environment. SBIRT+RM describes relevant strategies for improving recovery outcomes for individuals identified through primary care substance screening and defines primary care provider roles and responsibilities for sustained recovery support and long-term recovery maintenance. PMID- 27272993 TI - Consumer-Centered, Collaborative, and Comprehensive Care: The Core Essentials of Recovery-Oriented System of Care. AB - Recovery from substance abuse and mental health disorders represents a journey through which individuals move beyond treatment of provider-identified problems toward a path of achieving wellness and productive lives. Overcoming obstacles and barriers encountered along the recovery process, individuals reveal their own strengths and resilience necessary to cope, survive, and thrive in the face of adversity. Recovery-oriented system of care (ROSC) is a framework designed to address the multidimensional nature of recovery by creating a system for coordinating multiple systems, services, and supports that are person centered and build on the strengths and resiliencies of individuals, families, and communities. As is common knowledge among substance abuse and mental health providers, consumers often present with high rates of comorbidity, which complicates care. In addition, behavioral health consumers engage in risky health behaviors (e.g., smoking) at a disproportionate rate, which places them at increased risk for developing noncommunicable diseases. ROSCs are ideal for addressing the complicated and varied needs of consumers as they progress toward wellness. The challenges of creating an ROSC framework that is effective, efficient, and acceptable to consumers is formidable. It requires change on the part of agencies, organizations, providers, and consumers. The importance of comprehensive, integrated screening is highlighted as a critical component of ROSC. Key suggestions for initiating ROSC are offered. PMID- 27272994 TI - Implementation of Recovery Programming on an Inpatient Acute Psychiatric Unit and Its Impact on Readmission. AB - BACKGROUND: Recovery-oriented models of care are evidence based and have been shown to improve patient satisfaction and outcomes as well as decrease the percentage of readmissions to inpatient psychiatric units. METHODS: This quality improvement project was implemented on a 16-bed inpatient adult mental health unit in a Veterans Affairs Medical Center. Percentages of readmissions were compared throughout the course of implementation of the recovery model. Readmissions during the months of July-September were tabulated over 3 subsequent years and compared readmission percentages before recovery implementation, during the early stage of recovery implementation, and finally, during ongoing recovery implementation. RESULTS: A decrease in readmission percentages was seen with implementation of recovery-oriented care when comparing the same 3-month period over 3 years. CONCLUSION: After implementation of recovery-oriented care measures, there was a decrease in percentage of readmissions to the unit. In addition, this decrease was sustained and was shown to improve over time as recovery-oriented programming was further developed on the unit. These data suggest that Veterans Affairs Medical Centers should consider adding tools and procedures to successfully implement recovery programming on inpatient units and efforts should include direct involvement of patients in their own recovery journey, revision of policies and procedures to reflect the importance of recovery, thorough training of frontline staff regarding recovery principles, and transfer of recovery information directly from inpatient units to outpatient providers. PMID- 27272995 TI - The Alternative Peer Group: A Developmentally Appropriate Recovery Support Model for Adolescents. AB - Recovery as the goal for substance use disorder treatment has been a key component of the Substance Abuse and Mental Health Services Administration's mission for the past decade. Consistent with their mission, there is a call for research and development of recovery-oriented systems of care to support affected individuals through all stages of the recovery process. Evidence is emerging to support recovery practice and research for adults, but recovery-oriented models for adolescents are scant. The Alternative Peer Group (APG) is a comprehensive adolescent recovery support model that integrates recovering peers and prosocial activities into evidence-based clinical practice. Employing APG participants' own words, this article will describe the essential elements and three theoretical frameworks underlying the APG model to illustrate how the APG serves as a developmentally appropriate recovery support service for adolescents with substance use disorder. PMID- 27272996 TI - Houston Recovery Initiative: A Rich Case Study of Building Recovery Communities One Voice at a Time. AB - Recovery from alcohol and drug problems is a process of change through which an individual achieves control and improved quality of life. Recovery is a primary goal for individuals with substance use disorder as it provides hope that treatment and overall health are possible for every individual. More than 23 million Americans are in recovery from addiction to alcohol and other drugs.Recovery-oriented systems of care (ROSC) are networks of community services and peer support that help individuals and families achieve recovery from substances and improve overall health. ROSC is a strengths-based and person centered model that leverages existing community resources to address the needs of individuals and families as they progress through the journey of recovery. The ROSC model serves as the foundation of the Houston Recovery Initiative (HRI).The purpose of this article is to describe the history, development, and infrastructure of the HRI, which is a volunteer collaboration whose main goal is to educate the community on recovery and broaden the recovery safety net for people with substance use disorder in Houston, Texas. Since 2010, the HRI has grown to include more than 200 agencies across the spectrum of treatment and recovery support services in Houston so as to provide a resource for the community. Herein, we detail efforts to grow the HRI, lessons learned, future plans, and resources needed to move the HRI forward. PMID- 27272998 TI - Recovery in the 21st Century: From Shame to Strength. AB - Through the "war on drugs," the just-say-no campaign, and into the early years of this century, the overarching approach to substance use disorders (SUDs) called for a single outcome (abstinence) and a single methodology (spiritual connection with a higher power) as the remedy for SUDs. Those who did not become permanently abstinent or rejected the spiritual approach were seen as "not ready" or "in denial."A seismic shift in thinking about "addiction" and "recovery" began in earnest in the 1990s. In 2005, the Substance Abuse and Mental Health Services Administration brought together leaders of the treatment and recovery field for the historic National Summit on Recovery to develop broad-based consensus on guiding principles for recovery and elements of recovery-oriented systems of care.Major changes associated with the recovery-oriented approach include viewing SUDs as chronic, rather than acute, problems that require long-term support and focusing on recovery management rather than disease management. Complete abstinence is not an absolute requirement for wellness for all persons with SUDs. There are "many pathways to recovery," not only the 12-Step approach (White & Kurtz, 2006). Sustained recovery is self-directed and requires personal choices, the support of peers and allies, and community reinforcement as well as a strength-based approach and the use of research-based interventions. This Perspectives column addresses the historical context for the transformation toward a recovery-oriented system of care, highlights federal efforts to promote recovery-oriented approaches, and describes recovery-oriented terminology to reduce misconceptions, labeling, and stigmatization and promote recovery for individuals, families, and communities. PMID- 27272997 TI - Health Promotion in an Opioid Treatment Program: An Evidence-Based Nursing Quality Improvement Project. AB - Community assessment and review of the literature indicate that individuals supported in opioid treatment programs are at a significant disadvantage for access to preventative and primary healthcare. In addition, this population faces increased comorbidities and chronic disease. Finally, access to housing, nutritious food, and other social determinants of health is also a challenge for these individuals. This project, aimed at addressing healthcare disparities and improving health outcomes for the opioid treatment program client, was undertaken at a large, private, not-for-profit, community mental health center in an urban area. An education-practice partnership was created between the center and the local university's College of Nursing, which includes undergraduate and graduate programs. Working with administration, nurses, medical staff, and clinicians, the advanced practice nurse guided nursing practice change within the context of an interdisciplinary team to increase attention to clients' health needs. Outcomes included a more comprehensive nursing health assessment and increased attention to nursing care coordination. The partnership between the university and the facility continues with the goal of addressing clients' unmet healthcare needs and improving wellness via on-site intervention, referral, and education. PMID- 27272999 TI - An Interview With Anna Treloar, RN, MA, MPHC, PhD, Lecturer, School of Nursing and Midwifery, University of Newcastle, Callaghan, Australia. PMID- 27273000 TI - Recovery Management and Recovery-Oriented Systems of Care. PMID- 27273001 TI - Cannabis: Is There Any Good or Only Bad and Ugly? PMID- 27273002 TI - Part 2: Screening, Brief Intervention and Referral to Treatment Plus Recovery Management: A Proposed Model for Recovery-Oriented Primary Care. PMID- 27273003 TI - The role of surface basic amino acids of dengue virus NS3 helicase in viral RNA replication and enzyme activities. AB - Structure-based mutagenesis analysis on selected conserved surface basic residues of DENV NS3 helicase was performed using a selectable replicon and recombinant protein. We found a requirement for basic side chains of NS3 residues #225, #268, and #538 to activate viral RNA replication and ensure RNA-stimulated ATPase activity, and a critical role for R560 and R599 residues in maintaining NS3 helicase structure, linked to its biological function and catalytic activity. Three screened NS3 second-site mutations for R225A and R268A/E mutations elevated the functional RNA binding of NS3 helicase and compensated the replication defect of the original NS3 mutant replicons. PMID- 27273005 TI - Laser printing of resonant plasmonic nanovoids. AB - Hollow reduced-symmetry resonant plasmonic nanostructures possess pronounced tunable optical resonances in the UV-vis-IR range, being a promising platform for advanced nanophotonic devices. However, the present fabrication approaches require several consecutive technological steps to produce such nanostructures, making their large-scale fabrication rather time-consuming and expensive. Here, we report on direct single-step fabrication of large-scale arrays of hollow parabolic- and cone-shaped nanovoids in silver and gold thin films, using single pulse femtosecond nanoablation at high repetition rates. The lateral and vertical size of such nanovoids was found to be laser energy-tunable. Resonant light scattering from individual nanovoids was observed in the visible spectral range, using dark-field confocal microspectroscopy, with the size-dependent resonant peak positions. These colored geometric resonances in far-field scattering were related to excitation and interference of transverse surface plasmon modes in nanovoid shells. Plasmon-mediated electromagnetic field enhancement near the nanovoids was evaluated via finite-difference time-domain calculations for their model shapes simulated by three-dimensional molecular dynamics, and experimentally verified by means of photoluminescence microscopy and Raman spectroscopy. PMID- 27273004 TI - Pharmacokinetic Interactions Between Isavuconazole and the Drug Transporter Substrates Atorvastatin, Digoxin, Metformin, and Methotrexate in Healthy Subjects. AB - This article summarizes 4 phase 1 trials that explored interactions between the novel, triazole antifungal isavuconazole and substrates of the drug transporters breast cancer resistance protein (BCRP), multidrug and toxin extrusion protein-1 (MATE1), organic anion transporters 1/3 (OAT1/OAT3), organic anion-transporting polypeptide 1B1 (OATP1B1), organic cation transporters 1/2 (OCT1/OCT2), and P glycoprotein (P-gp). Healthy subjects received single doses of atorvastatin (20 mg; OATP1B1 and P-gp substrate), digoxin (0.5 mg; P-gp substrate), metformin (850 mg; OCT1, OCT2, and MATE1 substrate), or methotrexate (7.5 mg; BCRP, OAT1, and OAT3 substrate) in the presence and absence of clinical doses of isavuconazole (200 mg 3 times a day for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased mean area under the plasma concentration-time curves (90% confidence interval) of atorvastatin, digoxin, and metformin to 137% (129, 145), 125% (117, 134), and 152% (138, 168) and increased mean maximum plasma concentrations to 103% (88, 121), 133% (119, 149), and 123% (109, 140), respectively. Methotrexate parameters were unaffected by isavuconazole. There were no serious adverse events. These findings indicate that isavuconazole is a weak inhibitor of P-gp, as well as OCT1, OCT2, MATE1, or a combination thereof but not of BCRP, OATP1B1, OAT1, or OAT3. PMID- 27273008 TI - Temporal hollowing and other adverse effects after lateral orbital wall decompression. AB - PURPOSE: To evaluate the outcome and late postoperative complications after lateral orbital wall decompression in a series of patients with thyroid eye disease (TED). METHODS: One hundred and three patients operated in the period 1999-2013 were invited to participate in the study, and 84 were included after a median (range) follow-up time of 124 (13-188) months. The patients were interviewed, and preoperative and postoperative data were collected from hospital records. Photographs ('selfies') were obtained from 64 patients. Wilcoxon signed rank test was used to evaluate the change in pre- and postoperative data. RESULTS: On average, visual acuity was unchanged with a median value (range) of 1.0 (0.4-1.25) before to 1.0 (0-1.25) after surgery (p = 0.5). Intraocular pressure (IOP) was reduced from a median value (range) of 17 (9-26) to 15 (8-23) mmHg (p < 0.001). Median (range) Hertel values were 23 (15-30) mm preoperatively and 20 (12-26) mm postoperatively (p < 0.001) respectively. Mean (SD) reduction in proptosis was 3.6 (+/-2.1) mm. Oscillopsia was reported in 24 patients (29%), 42 (50%) experienced a change in temporal sensation, and four (5%) had new-onset diplopia. In 47 patients (56%), some degree of temporal hollowing was reported. Among 64 photographed patients, 38 (59%) had noticeable hollowing on examination of postoperative pictures. There was agreement of the patient's perception of temporal hollowing and the appearance in photographs in 26 of 37 patients (70%). CONCLUSION: Lateral orbital wall decompression has been considered a safe and effective procedure for treatment of TED. Serious side-effects are infrequent, but in rare circumstances, even blindness may occur. Less serious side-effects are relatively common. Among others, a significant number of the patients developed temporal hollowing after the procedure. The patients must be informed about the possible complications before surgery. PMID- 27273007 TI - Secondary Structure Prediction of Protein Constructs Using Random Incremental Truncation and Vacuum-Ultraviolet CD Spectroscopy. AB - A novel uracil-DNA degrading protein factor (termed UDE) was identified in Drosophila melanogaster with no significant structural and functional homology to other uracil-DNA binding or processing factors. Determination of the 3D structure of UDE is excepted to provide key information on the description of the molecular mechanism of action of UDE catalysis, as well as in general uracil-recognition and nuclease action. Towards this long-term aim, the random library ESPRIT technology was applied to the novel protein UDE to overcome problems in identifying soluble expressing constructs given the absence of precise information on domain content and arrangement. Nine constructs of UDE were chosen to decipher structural and functional relationships. Vacuum ultraviolet circular dichroism (VUVCD) spectroscopy was performed to define the secondary structure content and location within UDE and its truncated variants. The quantitative analysis demonstrated exclusive alpha-helical content for the full-length protein, which is preserved in the truncated constructs. Arrangement of alpha helical bundles within the truncated protein segments suggested new domain boundaries which differ from the conserved motifs determined by sequence-based alignment of UDE homologues. Here we demonstrate that the combination of ESPRIT and VUVCD spectroscopy provides a new structural description of UDE and confirms that the truncated constructs are useful for further detailed functional studies. PMID- 27273006 TI - Th2 and eosinophil responses suppress inflammatory arthritis. AB - Th2-eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2-eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis. PMID- 27273009 TI - Validity and reliability of a pictorial instrument for assessing perceived motor competence in Portuguese children. AB - BACKGROUND: It is important to assess young children's perceived Fundamental Movement Skill (FMS) competence in order to examine the role of perceived FMS competence in motivation toward physical activity. Children's perceptions of motor competence may vary according to the culture/country of origin; therefore, it is also important to measure perceptions in different cultural contexts. The purpose was to assess the face validity, internal consistency, test-retest reliability and construct validity of the 12 FMS items in the Pictorial Scale for Perceived Movement Skill Competence for Young Children (PMSC) in a Portuguese sample. METHODS: Two hundred one Portuguese children (girls, n = 112), 5 to 10 years of age (7.6 +/- 1.4), participated. All children completed the PMSC once. Ordinal alpha assessed internal consistency. A random subsamples (n = 47) were reassessed one week later to determine test-retest reliability with Bland-Altman method. Children were asked questions after the second administration to determine face validity. Construct validity was assessed on the whole sample with a Bayesian Structural Equation Modelling (BSEM) approach. The hypothesized theoretical model used the 12 items and two hypothesized factors: object control and locomotor skills. RESULTS: The majority of children correctly identified the skills and could understand most of the pictures. Test-retest reliability analysis was good, with an agreement ration between 0.99 and 1.02. Ordinal alpha values ranged from acceptable (object control 0.73, locomotor 0.68) to good (all FMS 0.81). The hypothesized BSEM model had an adequate fit. CONCLUSIONS: The PMSC can be used to investigate perceptions of children's FMS competence. This instrument can also be satisfactorily used among Portuguese children. PMID- 27273010 TI - DFT-Based Simulation and Experimental Validation of the Topotactic Transformation of MgAl Layered Double Hydroxides. AB - The thermal topotactic transformation mechanism of MgAl layered double hydroxides (LDHs) is investigated by a combined theoretical and experimental study. Thermogravimetric differential thermal analysis (TG-DTA) results reveal that the LDH phase undergoes four key endothermic events at 230, 330, 450, and 800 degrees C. DFT calculations show that the LDH decomposes into CO2 and residual O atoms via a monodentate intermediate at 330 degrees C. At 450 degrees C, the metal cations almost maintain their original distribution within the LDH(001) facet during the thermal dehydration process, but migrate substantially along the c-axis direction perpendicular to the (001) facet; this indicates that the metal arrangement/dispersion in the LDH matrix is maintained two-dimensionally. A complete collapse of the layered structure occurs at 800 degrees C, which results in a totally disordered cation distribution and many holes in the final product. The structures of the simulated intermediates are highly consistent with the observed in situ powder XRD data for the MgAl LDH sample calcined at the corresponding temperatures. Understanding the structural topotactic transformation process of LDHs would provide helpful information for the design and preparation of metal/metal oxides functional materials derived from LDH precursors. PMID- 27273011 TI - Gustilo type IIIC open tibia fractures with vascular repair: minimum 2-year follow-up. AB - PURPOSE: Salvage or amputation for grade 3C open fracture of tibia is not well responded question universally because of surgical innovations, cultural believes, difficulties in estimate the outcome, coasts, and different results in the literature. The aim of this study was to evaluate the surgical outcomes of Gustilo grade 3C open tibia fractures with at least two years follow-up in non military adults. METHODS: Twenty-two non-military patients with a mean age of 31.1 were operated with grade 3c open fractures at tibia level in last 10 years in our clinic. We evaluated them retrospectively and asked about their daily life, pain, and if present, about the wish for secondary amputation. We also asked if they would prefer a first day amputation rather than their present status. RESULTS: Mean operation time after the injury was 13 h. Seven patients had nerve injury. Mean operation number was 3.5. Eight patients (%36) (all due to circulatory problem) had to have amputation. All patients treated with temporary unilateral external fixation than converted to circular external fixators when soft tissue healing was completed. Two patients were reoperated because of deformity. Four patients needed revision surgery because of non-union. At long term follow, we had osteomyelitis in one patient. CONCLUSIONS: Scoring systems and the ischemic time are not the only predictors of amputation. The decision of the treatment mode should be made by the patient and the care team after discussing the options and outcomes rather than relying on a scoring system. PMID- 27273012 TI - Molecular Phylogeny, Diversity, and Bioprospecting of Endophytic Fungi Associated with wild Ethnomedicinal North American Plant Echinacea purpurea (Asteraceae). AB - The endophytic fungal community associated with the ethnomedicinal plant Echinacea purpurea was investigated as well as its potential for providing antifungal compounds against plant pathogenic fungi. A total of 233 endophytic fungal isolates were obtained and classified into 42 different taxa of 16 genera, of which Alternaria alternata, Colletotrichum dematium, and Stagonosporopsis sp. 2 are the most frequent colonizers. The extracts of 29 endophytic fungi displayed activities against important phytopathogenic fungi. Eight antifungal extracts were selected for chemical analysis. Forty fatty acids were identified by gas chromatography-flame-ionization detection (GC-FID) analysis. The compounds (-)-5 methylmellein and (-)-(3R)-8-hydroxy-6-methoxy-3,5-dimethyl-3,4 dihydroisocoumarin were isolated from Biscogniauxia mediterraneaEPU38CA crude extract. (-)-5-Methylmellein showed weak activity against Phomopsis obscurans, P. viticola, and Fusarium oxysporum, and caused growth stimulation of C. fragariae, C. acutatum, C. gloeosporioides, and Botrytis cinerea. (-)-(3R)-8-Hydroxy-6 methoxy-3,5-dimethyl-3,4-dihydroisocoumarin appeared slightly more active in the microtiter environment than 5-methylmellein. Our results indicate that E. purpurea lives symbiotically with different endophytic fungi, which are able to produce bioactive fatty acids and aromatic compounds active against important phytopathogenic fungi. The detection of the different fatty acids and aromatic compounds produced by the endophytic community associated with wild E. purpurea suggests that it may have intrinsic mutualistic resistance against phytopathogen attacks in its natural environment. PMID- 27273013 TI - Using Bayesian Adaptive Trial Designs for Comparative Effectiveness Research: A Virtual Trial Execution. AB - BACKGROUND: Bayesian and adaptive clinical trial designs offer the potential for more efficient processes that result in lower sample sizes and shorter trial durations than traditional designs. OBJECTIVE: To explore the use and potential benefits of Bayesian adaptive clinical trial designs in comparative effectiveness research. DESIGN: Virtual execution of ALLHAT (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) as if it had been done according to a Bayesian adaptive trial design. SETTING: Comparative effectiveness trial of antihypertensive medications. PATIENTS: Patient data sampled from the more than 42 000 patients enrolled in ALLHAT with publicly available data. MEASUREMENTS: Number of patients randomly assigned between groups, trial duration, observed numbers of events, and overall trial results and conclusions. RESULTS: The Bayesian adaptive approach and original design yielded similar overall trial conclusions. The Bayesian adaptive trial randomly assigned more patients to the better-performing group and would probably have ended slightly earlier. LIMITATIONS: This virtual trial execution required limited resampling of ALLHAT patients for inclusion in RE-ADAPT (REsearch in ADAptive methods for Pragmatic Trials). Involvement of a data monitoring committee and other trial logistics were not considered. CONCLUSION: In a comparative effectiveness research trial, Bayesian adaptive trial designs are a feasible approach and potentially generate earlier results and allocate more patients to better performing groups. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute. PMID- 27273014 TI - P/Q-type and T-type voltage-gated calcium channels are involved in the contraction of mammary and brain blood vessels from hypertensive patients. AB - AIM: Calcium channel blockers are widely used in cardiovascular diseases. Besides L-type channels, T- and P/Q-type calcium channels are involved in the contraction of human renal blood vessels. It was hypothesized that T- and P/Q-type channels are involved in the contraction of human brain and mammary blood vessels. METHODS: Internal mammary arteries from bypass surgery patients and cerebral arterioles from patients with brain tumours with and without hypertension were tested in a myograph and perfusion set-up. PCR and immunohistochemistry were performed on isolated blood vessels. RESULTS: The P/Q-type antagonist omega agatoxin IVA (10-8 mol L-1 ) and the T-type calcium blocker mibefradil (10-7 mol L-1 ) inhibited KCl depolarization-induced contraction in mammary arteries from hypertensive patients with no effect on blood vessels from normotensive patients. omega-Agatoxin IVA decreased contraction in cerebral arterioles from hypertensive patients. L-type blocker nifedipine abolished the contraction in mammary arteries. PCR analysis showed expression of P/Q-type (Cav 2.1), T-type (Cav 3.1 and Cav 3.2) and L-type (Cav 1.2) calcium channels in mammary and cerebral arteries. Immunohistochemical labelling of mammary and cerebral arteries revealed the presence of Cav 2.1 in endothelial and smooth muscle cells. Cav 3.1 was also detected in mammary arteries. CONCLUSION: P/Q- and T-type Cav are present in human internal mammary arteries and in cerebral penetrating arterioles. P/Q- and T-type calcium channels are involved in the contraction of mammary arteries from hypertensive patients but not from normotensive patients. Furthermore, in cerebral arterioles P/Q-type channels importance was restricted to hypertensive patients might lead to that T- and P/Q-type channels could be a new target in hypertensive patients. PMID- 27273015 TI - Evaluating quantitative proton-density-mapping methods. AB - Quantitative magnetic resonance imaging (qMRI) aims to quantify tissue parameters by eliminating instrumental bias. We describe qMRI theory, simulations, and software designed to estimate proton density (PD), the apparent local concentration of water protons in the living human brain. First, we show that, in the absence of noise, multichannel coil data contain enough information to separate PD and coil sensitivity, a limiting instrumental bias. Second, we show that, in the presence of noise, regularization by a constraint on the relationship between T1 and PD produces accurate coil sensitivity and PD maps. The ability to measure PD quantitatively has applications in the analysis of in vivo human brain tissue and enables multisite comparisons between individuals and across instruments. Hum Brain Mapp 37:3623-3635, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273017 TI - Transcriptional reprogramming and phenotypic switching associated with the adaptation of Lactobacillus plantarum C2 to plant niches. AB - Lactobacillus plantarum has been isolated from a large variety of ecological niches, thus highlighting its remarkable environmental adaptability as a generalist. Plant fermentation conditions markedly affect the functional features of L. plantarum strains. We investigated the plant niche-specific traits of L. plantarum through whole-transcriptome and phenotypic microarray profiles. Carrot (CJ) and pineapple (PJ) juices were chosen as model systems, and MRS broth was used as a control. A set of 3,122 genes was expressed, and 21 to 31% of genes were differentially expressed depending on the plant niche and cell physiological state. L. plantarum C2 seemed to specifically respond to plant media conditions. When L. plantarum was cultured in CJ, useful pathways were activated, which were aimed to sense the environment, save energy and adopt alternative routes for NAD(+) regeneration. In PJ the acidic environment caused a transcriptional switching, which was network-linked to an acid tolerance response involving carbohydrate flow, amino acid and protein metabolism, pH homeostasis and membrane fluidity. The most prominent phenotypic dissimilarities observed in cells grown in CJ and PJ were related to carbon and nitrogen metabolism, respectively. Summarising, a snapshot of a carrot and pineapple sensing and adaptive regulation model for L. plantarum C2 was proposed. PMID- 27273019 TI - Mechanistic Insight into Nanomolar Binding of Multivalent Neoglycopeptides to Wheat Germ Agglutinin. AB - Multivalent carbohydrate-protein interactions are frequently involved in essential biological recognition processes. Accordingly, multivalency is often also exploited for the design of high-affinity lectin ligands aimed at the inhibition of such processes. In a previous study (D. Schwefel et al., J. Am. Chem. Soc. 2010, 132, 8704-8719) we identified a tetravalent cyclopeptide-based ligand with nanomolar affinity to the model lectin wheat germ agglutinin (WGA). To unravel the structural features of this ligand required for high-affinity binding to WGA, we synthesized a series of cyclic and linear neoglycopeptides that differ in their conformational freedom as well as the number of GlcNAc residues. Combined evidence from isothermal titration calorimetry (ITC), enzyme linked lectin assays (ELLA), and dynamic light scattering (DLS) revealed different binding modes of tetra- and divalent ligands and that conformational preorganization of the ligands by cyclization is not a prerequisite for achieving high binding affinities. The high affinities of the tetravalent ligands rather stem from their ability to form crosslinks between several WGA molecules. The results illustrate that binding affinities and mechanisms are strongly dependent on the used multivalent system which offers opportunities to tune and control binding processes. PMID- 27273020 TI - The potential of incorporation of binary salts and ionic liquid in P(VP-co-VAc) gel polymer electrolyte in electrochemical and photovoltaic performances. AB - In this study, dye-sensitized solar cells (DSSCs) has been assembled with poly(1 vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VAc)) gel polymer electrolytes (GPEs) which have been incorporated with binary salt and an ionic liquid. The potential of this combination was studied and reported. The binary salt system GPEs was having ionic conductivity and power conversion efficiency (PCE) that could reach up to 1.90 * 10(-3) S cm(-1) and 5.53%, respectively. Interestingly, upon the addition of the ionic liquid, MPII into the binary salt system the ionic conductivity and PCE had risen steadily up to 4.09 * 10(-3) S cm(-1) and 5.94%, respectively. In order to know more about this phenomenon, the electrochemical impedance studies (EIS) of the GPE samples have been done and reported. Fourier transform infrared studies (FTIR) and thermogravimetric analysis (TGA) have also been studied to understand more on the structural and thermal properties of the GPEs. The Nyquist plot and Bodes plot studies have been done in order to understand the electrochemical properties of the GPE based DSSCs and Tafel polarization studies were done to determine the electrocatalytic activity of the GPE samples. PMID- 27273018 TI - Emerging hepatic syndromes: pathophysiology, diagnosis and treatment. AB - Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic options for patients with emerging hepatic syndromes in cirrhosis, namely the hepatorenal, hepato-adrenal and hepatopulmonary syndrome. The hepatorenal syndrome is a well-recognized complication of advanced cirrhosis and is usually associated with an accelerated course to death unless liver transplantation is performed. The hepatopulmonary syndrome is often missed in the evaluation of patients with cirrhosis; however, early recognition is essential for the efficient management of individual patients. The hepato-adrenal syndrome, although not fully characterized, offers an exciting field for research and potential therapeutic interventions. PMID- 27273022 TI - ACL rupture and joint laxity progression: a quantitative in vivo analysis. AB - PURPOSE: Benefits of an early reconstruction and the optimal time lapse between injury and surgery to reduce the effects of altered kinematics in ACL-deficient knees are still controversial. AIM: The aim of this study was to clarify, through a quantitative in vivo evaluation, the effects of the time lapse between ACL injury and surgery in terms of changes in the pre-operative knee laxity. METHODS: An in vivo study was performed on 99 patients who underwent ACL surgery. Just before the graft fixation, six laxity tests were performed for all the subjects at manual-maximum load: anterior-posterior displacement and internal-external rotation at 30 degrees and 90 degrees of knee flexion (AP30, AP90, IE30, IE90) as well as varus-valgus rotation (VV0, VV30) at 0 degrees and 30 degrees of flexion. Kinematics data were acquired by a navigation system. The Spearman rank correlation was used to assess correlation between rank and continuous data. Significance was set at P = 0.05. RESULTS: The analysis highlighted a significant influence of the injury-to-surgery time lapse on VV0 and AP90 compared with pre operative laxity levels. Meniscus status also significantly affected the pre operative laxity in the VV0 (Spearman's rho = 0.203, P = 0.038; GLM with meniscal correction partial eta = 0.27, P = 0.007) and AP90 (Spearman's rho = 0.329, P = 0.001; GLM with meniscal correction partial eta = 0.318, P = 0.017) tests. CONCLUSION: The main finding of this study is that patients with ACL rupture and a higher injury-to-surgery time present higher values of knee laxity involving AP90 displacement and VV30 rotation. Clinical relevance of the study is that ACL deficient joint laxity, involving anterior-posterior displacement at 90 degrees of knee flexion and varus-valgus rotation at 0 degrees of flexion, is significantly affected by the lapse of injury-to-surgery time. This highlights the importance of considering the effects of delaying surgery when managing patients with such deficiency. PMID- 27273023 TI - Effect of chronic somatic diseases on the course of late-life depression. AB - OBJECTIVE: To examine the influence of specific chronic somatic diseases and overall somatic diseases burden on the course of depression in older persons. METHODS: This was a prospective cohort study with a 2-year follow-up. Participants were depressed persons (n = 285) from the Netherlands Study of Depression in Older Persons. The presence of chronic somatic diseases was based on self-report. Diagnosis of depression was assessed with the Composite International Diagnostic Interview, and severity of depression was measured with the Inventory of Depressive Symptomatology Self-report. RESULTS: Cardiovascular diseases (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.02-2.72, p = 0.041), musculoskeletal diseases (OR = 1.71, 95% CI = 1.04-2.80, p = 0.034), and the number of chronic somatic diseases (OR = 1.37, 95% CI = 1.16-1.63, p < 0.001) were associated with having a depressive disorder at 2-year follow-up. Furthermore, chronic non-specific lung diseases, cardiovascular diseases, musculoskeletal diseases, cancer, or cumulative somatic disease burden were associated with a chronic course of depression. CONCLUSIONS: Somatic disease burden is associated with a poor course of late-life depression. The course of late-life depression is particularly unfavorable in the presence of chronic non specific lung diseases, cardiovascular diseases, musculoskeletal diseases, and cancer. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273025 TI - Calling in at work: Acute care nursing cell phone policies. PMID- 27273024 TI - Neural substrates and behavioral profiles of romantic jealousy and its temporal dynamics. AB - Jealousy is not only a way of experiencing love but also a stabilizer of romantic relationships, although morbid romantic jealousy is maladaptive. Being engaged in a formal romantic relationship can tune one's romantic jealousy towards a specific target. Little is known about how the human brain processes romantic jealousy by now. Here, by combining scenario-based imagination and functional MRI, we investigated the behavioral and neural correlates of romantic jealousy and their development across stages (before vs. after being in a formal relationship). Romantic jealousy scenarios elicited activations primarily in the basal ganglia (BG) across stages, and were significantly higher after the relationship was established in both the behavioral rating and BG activation. The intensity of romantic jealousy was related to the intensity of romantic happiness, which mainly correlated with ventral medial prefrontal cortex activation. The increase in jealousy across stages was associated with the tendency for interpersonal aggression. These results bridge the gap between the theoretical conceptualization of romantic jealousy and its neural correlates and shed light on the dynamic changes in jealousy. PMID- 27273026 TI - A multi-wavelength, laser-based optical spectroscopy device for breast density and breast cancer risk pre-screening. AB - Optical Breast Spectroscopy (OBS) has been shown to predict mammographic breast density, a strong breast cancer risk factor. OBS is a low-cost technique applicable at any age. OBS information may be useful for personalizing breast cancer screening programs based on risk to improve consensus on and adherence to screening guidelines. To facilitate the use of OBS in population-wide studies, a research prototype OBS device was modified to make it portable and cheaper and to require less operator interaction. Two major changes were made: (1) the broadband light source was replaced with a laser module with 13 individual wavelengths turned on sequentially, enabling the use of photodiode detectors instead of a spectrometer, and (2) the light sources and detectors were placed in fixed positions within 4 sizes of cup, eliminating the need for placement by the operator. Wavelengths were selected using data from two previous studies. The reduction in spectral content did not significantly reduce the ability to distinguish between different risk groups. Positions for the light sources and detectors were chosen based on Monte Carlo simulations to match the optically interrogated volumes of the original device. Two light sources and six detectors per cup were used in the final design. PMID- 27273027 TI - [Influenza outbreak in weaners with involvement of Mycoplasma hyorhinis and Haemophilus parasuis. A case report]. AB - In a closed farrow-to-finish piglet producing farm 80% of 7-week-old piglets displayed respiratory disease with a 5% mortality rate. In addition to purulent bronchopneumonia in combination with interstitial pneumonia predominantly in the apical and middle lobes, fibrinous serositis was present in the thoracic and abdominal cavities. Further investigations succeeded in confirming the non pandemic strain of porcine influenza A virus (FLUAVsw) subtype H1avN1. The molecular genetic studies on Mycoplasma (M.) hyopneumoniae and porcine reproductive and respiratory syndrome virus were negative, whereas M. hyorhinis and Haemophilus parasuis were isolated from serous membranes. The possible importance of the underrated M. hyorhinis as a cofactor for viral infections should be emphasized and we demonstrated that the cause of apical lobe pneumonia is not restricted to M. hyopneumoniae. Mother pigs had been vaccinated with an influenza vaccine covering the subtype H1avN1. Only 33% of the examined piglets had maternal antibodies in the 7th week of life. The difficulty of prophylaxis of infections by FLUAVsw in weaners due to lack of vaccine authorization for piglets before their 56th day is reflected by this observation. PMID- 27273029 TI - Looking for citizen-centered communication: dialogues between radiological protection or nuclear safety specialists and media professionals. AB - What happens when radiological protection or nuclear safety officials get together with media professionals to talk about public communication on ionizing radiation risks? Do they have common views of the challenges and ways to meet these? This practical article reports on dialogue workshops organized by the EAGLE project in four European countries (France, Poland, Romania, and Slovenia). Common findings are classed and presented by themes, including inter alia: crisis versus everyday communication; mediated versus direct communication; sources, actors, roles and responsibilities; language and format; trust and confidence, balance in reporting and development of risk culture; nuclear industry promotion versus citizen-centered risk communication. The article also presents reflections from an expanded international workshop (RICOMET, June 2015). It echoes the participants in calling for a platform for ongoing dialogue between information sources and transmitters, in the interest of building solid relationships, risk culture and public understanding on ionizing radiation. PMID- 27273028 TI - Pupal diapause termination in Bactrocera minax: an insight on 20-hydroxyecdysone induced phenotypic and genotypic expressions. AB - The Chinese citrus fruit fly, Bactrocera minax, is an economically important pest of citrus. It exhibits pupal diapause from November to May to combat harsh environmental conditions. Such a long pupal diapause is a barrier for laboratory rearing and development of control strategies against this pest. In the present study, 20-hydroxyecdysone (20E) was used to break pupal diapause of B. minax by topical application. After diapause termination by 20E treated, the pupal ontogenetic processes were observed along the temporal trajectory. The pupal response time to 20E was estimated by detecting the relative expression of 20E responsive genes at different times after 20E-treatment. Results revealed that 20E could effectively terminate the pupal diapause in a dose-dependent manner and significantly shorten the time for 50% adult emergence (Et50). 20E response genes, including ecr, broad and foxo, were up-regulated within 72h, indicating these genes are involved in pupal metamorphosis and diapause termination processes. Morphological changes showed the pupal metamorphosis began ~7 days after 20E-treatment at 22 degrees C. This study does not only pave the way for artificial rearing in the laboratory through manipulating of pupal diapause termination, but also deepens our understanding of the underlying pupal diapause termination mechanism of B. minax. PMID- 27273031 TI - Intestinal ultrasound in inflammatory bowel disease. PMID- 27273030 TI - Structural Ensembles of Membrane-bound alpha-Synuclein Reveal the Molecular Determinants of Synaptic Vesicle Affinity. AB - A detailed characterisation of the molecular determinants of membrane binding by alpha-synuclein (alphaS), a 140-residue protein whose aggregation is associated with Parkinson's disease, is of fundamental significance to clarify the manner in which the balance between functional and dysfunctional processes are regulated for this protein. Despite its biological relevance, the structural nature of the membrane-bound state alphaS remains elusive, in part because of the intrinsically dynamic nature of the protein and also because of the difficulties in studying this state in a physiologically relevant environment. In the present study we have used solid-state NMR and restrained MD simulations to refine structure and topology of the N-terminal region of alphaS bound to the surface of synaptic-like membranes. This region has fundamental importance in the binding mechanism of alphaS as it acts as to anchor the protein to lipid bilayers. The results enabled the identification of the key elements for the biological properties of alphaS in its membrane-bound state. PMID- 27273032 TI - Introduction. PMID- 27273033 TI - Biosimilar and innovator anti-Tumour Necrosis Factor (TNF) or lymphocyte trafficking blockade: Which one to select? PMID- 27273034 TI - Organising infusions: Application administration and complications. PMID- 27273035 TI - Iron and vitamin D deficiency in inflammatory bowel disease. PMID- 27273036 TI - Research topic: Health economics of biological agents in Australia. PMID- 27273037 TI - Dysplasia surveillance - a practical guide. PMID- 27273038 TI - Imaging in IBD: Capsule, NBI, and chromoendoscopy. PMID- 27273039 TI - How to fund IBD nurses. PMID- 27273040 TI - Research topic: Managing compassionate therapy-the role of the virtual clinic. PMID- 27273041 TI - In the IBD Unit: Summary. PMID- 27273042 TI - Rearrangement of mitochondrial pyruvate dehydrogenase subunit dihydrolipoamide dehydrogenase protein-protein interactions by the MDM2 ligand nutlin-3. AB - Drugs targeting MDM2's hydrophobic pocket activate p53. However, these agents act allosterically and have agonist effects on MDM2's protein interaction landscape. Dominant p53-independent MDM2-drug responsive-binding proteins have not been stratified. We used as a variable the differential expression of MDM2 protein as a function of cell density to identify Nutlin-3 responsive MDM2-binding proteins that are perturbed independent of cell density using SWATH-MS. Dihydrolipoamide dehydrogenase, the E3 subunit of the mitochondrial pyruvate dehydrogenase complex, was one of two Nutlin-3 perturbed proteins identified fours hour posttreatment at two cell densities. Immunoblotting confirmed that dihydrolipoamide dehydrogenase was induced by Nutlin-3. Depletion of MDM2 using siRNA also elevated dihydrolipoamide dehydrogenase in Nutlin-3 treated cells. Mitotracker confirmed that Nutlin-3 inhibits mitochondrial activity. Enrichment of mitochondria using TOM22+ immunobeads and TMT labeling defined key changes in the mitochondrial proteome after Nutlin-3 treatment. Proximity ligation identified rearrangements of cellular protein-protein complexes in situ. In response to Nutlin-3, a reduction of dihydrolipoamide dehydrogenase/dihydrolipoamide acetyltransferase protein complexes highlighted a disruption of the pyruvate dehydrogenase complex. This coincides with an increase in MDM2/dihydrolipoamide dehydrogenase complexes in the nucleus that was further enhanced by the nuclear export inhibitor Leptomycin B. The data suggest one therapeutic impact of MDM2 drugs might be on the early perturbation of specific protein-protein interactions within the mitochondria. This methodology forms a blueprint for biomarker discovery that can identify rearrangements of MDM2 protein-protein complexes in drug-treated cells. PMID- 27273043 TI - Immunotherapy: Study deciphers enigmatic mechanism of PD-L1 overexpression. PMID- 27273045 TI - The role of Internet resources in clinical oncology: promises and challenges. AB - The Internet is a valuable tool that continues to revolutionize many aspects of our lives; however, the ability to disseminate diverse data across populations and nations presents both opportunities and challenges. Online resources are increasingly used in health care, providing wider access to information for patients, researchers, and clinicians. At the turn of the millennium, the National Cancer Institute (NCI) predicted that Internet-based technologies would create a revolution in communication for oncology professionals and patients with cancer. Herein, findings from the NCI's Health Information National Trends Survey are reviewed to give insight into how Internet trends related to oncology patients are evolving. Future trends are discussed, including examples of 'connected health' in oncology; the spread of mobile and ubiquitous access points to Internet-hosted information; the diffusion of devices, sensors, and apps; the spread of personal data sharing; and an evolution in how networks can support person-centred and family-centred care. PMID- 27273046 TI - A Supramolecularly Activated Radical Cation for Accelerated Catalytic Oxidation. AB - Tuning the activity of radicals is crucial for radical reactions and radical based materials. Herein, we report a supramolecular strategy to accelerate the Fenton reaction through the construction of supramolecularly activated radical cations. As a proof of the concept, cucurbit[7]uril (CB[7]) was introduced, through host-guest interactions, onto each side of a derivative of 1,4 diketopyrrolo[3,4-c]pyrrole (DPP), a model dye for Fenton oxidation. The DPP radical cation, the key intermediate in the oxidation process, was activated by the electrostatically negative carbonyl groups of CB[7]. The activation induced a drastic decrease in the apparent activation energy and greatly increased the reaction rate. This facile supramolecular strategy is a promising method for promoting radical reactions. It may also open up a new route for the catalytic oxidation of organic pollutants for water purification and widen the realm of supramolecular catalysis. PMID- 27273044 TI - Towards a new classification of gastroenteropancreatic neuroendocrine neoplasms. AB - Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a heterogeneous group of tumours associated with variable clinical presentations, growth rates, and prognoses. To improve the management of GEP-NENs, the WHO developed a classification system that enables tumours to be graded based on markers of cell proliferation in biopsy specimens. Indeed, histopathology has been a mainstay in the diagnosis of GEP-NENs, and the WHO grading system facilitates therapeutic decision-making; however, considerable intratumoural heterogeneity, predominantly comprising regional variations in proliferation rates, complicates the evaluation of tumour biology. The use of molecular imaging modalities to delineate the most-aggressive cell populations is becoming more widespread. In addition, molecular profiling is increasingly undertaken in the clinical setting, and genomic studies have revealed a number of chromosomal alterations in GEP-NENs, although the 'drivers' of neoplastic development have not been identified. Thus, our molecular understanding of GEP-NENs remains insufficient to inform on patient prognosis or selection for treatments, and the WHO classification continues to form the basis for management of this disease. Nevertheless, our increasing understanding of the molecular genetics and biology of GEP-NENs has begun to expose flaws in the WHO classification. We describe the current understanding of the molecular characteristics of GEP-NENs, and discuss how advances in molecular profiling measurements, including assays of circulating mRNAs, are likely to influence the management of these tumours. PMID- 27273060 TI - Emergency airway management: What are the roles for surgical cricothyroidotomy and the Ventrain((r)) device? PMID- 27273047 TI - Sulfation of the FLAG epitope is affected by co-expression of G protein-coupled receptors in a mammalian cell model. AB - G protein-coupled receptors (GPCRs) are important therapeutic targets and therefore extensively studied. Like most transmembrane proteins, there has been considerable difficulty in developing reliable specific antibodies for them. To overcome this, epitope tags are often used to facilitate antibody recognition in studies on fundamental receptor signalling and trafficking. In our study of cannabinoid CB1/dopamine D2 interactions we sought to generate HEK293 cells expressing FLAG-tagged D2 for use in antibody-based assays of GPCR localisation and trafficking activity, however observed that stable FLAG-hD2 expression was particularly challenging to maintain. In contrast, when expressed in cell lines expressing hCB1 robust and stable FLAG-hD2 expression was observed. We hypothesised that co-expression of CB1 might stabilise surface FLAG-hD2 expression, and therefore investigated this further. Here, we describe the observation that co-expression of either cannabinoid CB1 or CB2 receptors in HEK293 decreases the sulfation of a FLAG epitope appended at the N-terminus of the dopamine D2 receptor. Sulfation alters epitope recognition by some anti-FLAG antibodies, leading to the detection of fewer receptors, even though expression is maintained. This demonstrates that cannabinoid receptor expression modifies posttranslational processing of the FLAG-hD2 receptor, and importantly, has wider implications for the utilisation and interpretation of receptor studies involving epitope tags. PMID- 27273061 TI - Postoperative environmental anesthetic vapour concentrations following removal of the airway device in the operating room versus the postanesthesia care unit. AB - PURPOSE: This study was designed to compare waste anesthetic gas (WAG) concentrations within patients' breathing zones after removal of the patient's airway device in the postanesthesia care unit (PACU) vs in the operating room (OR). METHODS: Following Research Ethics Board approval and patient consent, we recruited patients undergoing surgery who received volatile anesthesia via an endotracheal tube or supraglottic airway. Patients had their airway device removed in the OR or in the PACU depending on the attending anesthesiologist's preference. Upon the patient's arrival in the PACU, concentrations of exhaled sevoflurane and desflurane were measured at their breathing zone (i.e., 15 cm from the patient's mouth and nose) using a single-beam infrared spectrophotometer. RESULTS: Seventy patients were recruited during the five-month study period. The median [interquartile range] WAG levels in the patients' breathing zones were higher when their airway devices were removed in the PACU vs in the OR. The WAG levels for sevoflurane were 0.7 [0.4-1.1] parts per million (ppm) vs 0.5 [0.4-0.7] ppm, respectively; median difference, 0.3; 95% confidence interval (CI), 0.1 to 0.6; P = 0.04. The WAG levels for desflurane were 2.4 [1.2 3.4] ppm vs 4.1 [2.5-5.2] ppm, respectively; median difference, 1.5; 95% CI, 0.3 to 2.7; P = 0.04. CONCLUSIONS: After a volatile-based anesthetic, our results suggest that removal of the airway device in the PACU vs in the OR increases the amount of waste anesthetic gas in a patient's breathing zone and thus potentially in the PACU nurse's working zone. PMID- 27273063 TI - X-Ray absorption spectra of microsolvated metal cations. AB - Core excited states in clusters or bulk medium are known to undergo a process of internal ionisation, whereby the excited electron delocalises throughout the medium. This delocalisation is visible in the shifting and broadening of lines in X-ray absorption spectra, and it impacts the electronic decay initiated by photoabsorption. In this paper we study the delocalisation of electrons excited from the 1s core orbital of Na(+) and Mg(2+) ions in microsolvated Na(+)(H2O)m and Mg(2+)(H2O)m clusters (m = 1-6) by computing the X-ray absorption spectra and electron distributions in different core excited states. We show that addition of water ligands to the ion leads to more and more pronounced delocalisation of the core-to-valence 1s -> 3p and core-to-Rydberg 1s -> 4p excitations. Even for the compact 1s -> 3p excitation the excited electron is mostly located on the water molecules when the solvation shell is complete. We also found that the degree of delocalisation strongly depends on the cluster geometry and the ionic charge. These results indicate that even in small microsolvated clusters delocalisation of core excited electrons is substantial and will affect the following electronic decay. The accuracy and transferability of our results are corroborated by the good agreement between our XAS spectra of microsolvated Na(+) and experimental X ray absorption spectra of dilute NaCl solutions. PMID- 27273062 TI - A Novel System for Estimating Residual Disease and Pathologic Response to Neoadjuvant Treatment of Prostate Cancer. AB - BACKGROUND: Pathologic variables that characterize response of prostate carcinoma to current neoadjuvant therapy have not been characterized in detail. This study reports (i) the histological features of prostate cancer treated with abiraterone and enzalutamide and inter-pathologist variance in identifying these features, and (ii) the effect of the novel androgen deprivation agents on residual cancer volume. METHODS: We reviewed sections of prostatectomies from 37 patients treated with neoadjuvant agents and 22 untreated patients, tabulated the frequency of nine features of cancer (intact cancer glands, isolated cancer cells, poorly formed glands, cribriform architecture, clear spaces, intraductal carcinoma, solid sheets of cancer cells, prominent nucleoli, and previously described ABC grouping) and two features of benign glands (prominent basal cells and coalescent corpora amylacea). We used several methods, including a novel metric (visual grid system), to estimate residual tumor volume. RESULTS: The most highly reproducible features were ABC grouping (kappa = 0.56-0.7), presence of intraductal carcinoma (kappa = 0.34-0.72), cribriform architecture (kappa = 0.42-0.68), solid sheets of tumor cells (kappa = 0.44-0.56), and coalescent corpora amylacea (kappa = 0.4 0.54). Among poorly reproducible features were prominent nucleoli (kappa = 0.03 0.11), clear spaces (kappa = 0.05-0.07), and poorly formed cancer glands (kappa = 0.02-0.1). Determination of tumor mass was excellent regardless of the method used-maximum tumor size (kappa = 0.9-0.94), tumor area (kappa = 0.94-0.96), and grid-based tumor cellularity (kappa = 0.9). CONCLUSIONS: We propose using a set of parameters including maximum tumor size, tumor area/volume, cellularity, volume, and ABC grouping for evaluating radical prostatectomies post-neoadjuvant therapy. Prostate 76:1285-1292, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273064 TI - Requirements for nucleocapsid-mediated regulation of reverse transcription during the late steps of HIV-1 assembly. AB - HIV-1 is a retrovirus replicating within cells by reverse transcribing its genomic RNA (gRNA) into DNA. Within cells, virus assembly requires the structural Gag proteins with few accessory proteins, notably the viral infectivity factor (Vif) and two copies of gRNA as well as cellular factors to converge to the plasma membrane. In this process, the nucleocapsid (NC) domain of Gag binds to the packaging signal of gRNA which consists of a series of stem-loops (SL1-SL3) ensuring gRNA selection and packaging into virions. Interestingly, mutating NC activates a late-occurring reverse transcription (RT) step in producer cells, leading to the release of DNA-containing HIV-1 particles. In order to decipher the molecular mechanism regulating this late RT, we explored the role of several key partners of NC, such as Vif, gRNA and the cellular cytidine deaminase APOBEC3G that restricts HIV-1 infection by targeting the RT. By studying combinations of deletions of these putative players, we revealed that NC, SL1-SL3 and in lesser extent Vif, but not APOBEC3G, interplay regulates the late RT. PMID- 27273065 TI - Plant growth promoting potential and phylogenetic characteristics of a lichenized nitrogen fixing bacterium, Enterobacter cloacae. AB - Lichens are complex symbiotic association of mycobionts, photobionts, and bacteriobionts, including chemolithotropic bacteria. In the present study, 46 lichenized bacteria were isolated by conventional and enrichment culture methods on nitrogen-free bromothymol blue (NFb) medium. Only 11 of the 46 isolates fixed nitrogen on NFb and had reduced acetylene. All these 11 isolates had also produced siderophore and 10 of them the IAA. Further, ammonia production was recorded from nine of these nitrogen fixers (NF). On molecular characterization, 16 S rRNA sequencing recorded that, nine NF belonged to Proteobacteria, within Gammaproteobacteria, and were closely related to Enterobacter sp. with a maximum similarity to Enterobacter cloacae. Each one of our NF isolates was aligned closely to Enterobacter pulveris strain E443, Cronobacter sakazakii strain PNP8 and Providencia rettgeri strain ALK058. Notably, a few strains we examined found to possess plant growth promoting properties. This is the first report of Enterobacter sp. from lichens which may be inhabit lichen thalli extrinsically or intrinsically. PMID- 27273066 TI - The effect of simulation-based mastery learning on thoracentesis referral patterns. AB - Internal medicine (IM) residents and hospitalist physicians commonly perform thoracenteses. National data show that thoracenteses are also frequently referred to other services such as interventional radiology (IR), increasing healthcare costs. Simulation-based mastery learning (SBML) is an effective method to boost physicians' procedural skills and self-confidence. This study aimed to (1) assess the effect of SBML on IM residents' simulated thoracentesis skills and (2) compare thoracentesis referral patterns, self-confidence, and reasons for referral between traditionally trained residents (non-SBML-trained), SBML-trained residents, and hospitalist physicians. A random sample of 112 IM residents at an academic medical center completed thoracentesis SBML from December 2012 to May 2015. We surveyed physicians caring for hospitalized patients with thoracenteses during the same time period and compared referral patterns, self-confidence, and reasons for referral. SBML-trained resident thoracentesis skills improved from a median of 57.6% (interquartile range [IQR] 43.3-76.9) at pretest to 96.2% (IQR 96.2-100.0) at post-test (P < 0.001). Surveys demonstrated that traditionally trained residents were more likely to refer to IR and cited lower confidence as reasons. SBML-trained residents were more likely to perform bedside thoracenteses. Hospitalist physicians were most likely to refer to pulmonary medicine and cited lack of time to perform the procedure as the main reason. SBML trained residents were most confident about their thoracentesis skills, despite hospitalist physicians having more experience. This study identifies confidence and time as reasons physicians refer thoracenteses rather than perform them at the bedside. Thoracentesis SBML boosts skills and promotes bedside procedures that are safe and less expensive than referrals. Journal of Hospital Medicine 2016;11:792-795. (c) 2016 Society of Hospital Medicine. PMID- 27273067 TI - A systematic review and meta-analysis of randomized controlled trials of the effect of barley beta-glucan on LDL-C, non-HDL-C and apoB for cardiovascular disease risk reductioni-iv. AB - BACKGROUND/OBJECTIVES: There has been recent interest in barley as a therapeutic food owing to its high content of beta-glucan (beta-glucan), a viscous soluble fiber recognized for its cholesterol-lowering properties. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the cholesterol-lowering potential of barley beta-glucan on low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (apoB) for cardiovascular disease (CVD) risk reduction. METHODS: MEDLINE, Embase, CINAHL and the Cochrane CENTRAL were searched. We included RCTs of ?3-week duration assessing the effect of diets enriched with barley beta-glucan compared with controlled diets on LDL-C, non-HDL-C or apoB. Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by the Cochran Q-statistic and quantified by the I2 statistic. RESULTS: Fourteen trials (N=615) were included in the final analysis. A median dose of 6.5 and 6.9 g/day of barley beta-glucan for a median duration of 4 weeks significantly reduced LDL-C (MD=-0.25 mmol/l (95% CI: -0.30, -0.20)) and non-HDL C (MD=-0.31 mmol/l (95% CI: -0.39, -0.23)), respectively, with no significant changes to apoB levels, compared with control diets. There was evidence of considerable unexplained heterogeneity in the analysis of non-HDL-C (I2=98%). CONCLUSIONS: Pooled analyses show that barley beta-glucan has a lowering effect on LDL-C and non-HDL-C. Inclusion of barley-containing foods may be a strategy for achieving targets in CVD risk reduction. PMID- 27273068 TI - Key determinants of energy expenditure in cancer and implications for clinical practice. AB - Great discrepancies exist in the reported prevalence of altered energy metabolism (hypo- or hypermetabolism) in cancer patients, which is likely due to the vast array of phenomena that can affect energy expenditure in these patients. The purpose of this review was to critically evaluate key determinants of energy expenditure in cancer and the relevance for clinical practice. Resting energy expenditure (REE) is the largest and most commonly measured component of total energy expenditure. In addition to the energetic demand of the tumor itself, REE may be increased due to changes in inflammation, body composition and brown adipose tissue activation. Energy expenditure from physical activity is often lower in cancer compared with healthy populations, and there is evidence to suggest that the thermic effect of food might also be blunted and affected by cancer therapy. Although accurate assessment of energy metabolism is a cornerstone of adequate nutritional therapy, prediction methods often do not capture the true energy expenditure of most cancer patients. In fact, limits of agreement of prediction equations may range from 40% below to 30% above measured REE. Such variability highlights the need for a more comprehensive understanding of energy expenditure in cancer and the value of accurately assessing the energy needs of these patients. PMID- 27273069 TI - Misreport of energy intake assessed with food records and 24-h recalls compared with total energy expenditure estimated with DLW. AB - BACKGROUND/OBJECTIVES: The accuracy of dietary assessment methods has rarely been validated using precise techniques. The objective of this work was to evaluate the validity of energy intake (EI) estimated with food records (FRs) and 24-h recalls (24hRs) against total energy expenditure (EE) estimated by the doubly labeled water (DLW) method. In addition, the magnitude of EI under-reporting was assessed along with its associated characteristics. SUBJECTS/METHODS: The studied group included 83 adults between 20 and 60 years of age who were recruited from a population-based sample. Within-person variation-adjusted means of EI estimated from two FRs and three 24hRs were compared with EE estimated using the DLW method multiple-point protocol. The Wilcoxon signed-rank test was used to assess the differences between EI and EE, whereas Bland-Altman and survival-agreement plots assessed the agreement between the estimates. RESULTS: The mean EE (2540 kcal) was greater than the mean reported EI for both dietary assessment methods (FR: 1774 kcal; 24hR: 1658 kcal, P<0.01). The frequency of under-reporting was lower (20%) for EI estimated with the 24hR than that estimated with the FR (32%). Men presented lower magnitude of under-reported EI than women did. For women, differences between EI and EE were lower with FR than with 24hR. Overall, FR and 24hR showed similar performance. The mean under-reported EI was ~30% for both methods. CONCLUSIONS: Irregular meal habits, smoking and low education were associated with the under-report of EI. Both FR and 24hR are subjected to bias suggesting the need of refining the procedures applied in dietary assessment methods. PMID- 27273070 TI - Deep data science to prevent and treat growth faltering in Maya children. PMID- 27273072 TI - Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid induced epileptiform activity. AB - BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy. PMID- 27273073 TI - Fgf8 signaling for development of the midbrain and hindbrain. AB - In this paper, we review how midbrain and hindbrain are specified. Otx2 and Gbx2 are expressed from the early phase of development, and their expression abuts at the midbrain hindbrain boundary (MHB), where Fgf8 expression is induced, and functions as an organizing molecule for the midbrain and hindbrain. Fgf8 induces En1 and Pax2 expression at the region where Otx2 is expressed to specify midbrain. Fgf8 activates Ras-ERK pathway to specify hindbrain. Downstream of ERK, Pea3 specifies isthmus (rhombomere 0, r0), and Irx2 may specify r1, where the cerebellum is formed. PMID- 27273071 TI - Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children. AB - BACKGROUND/OBJECTIVES: Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. SUBJECTS/METHODS: The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). RESULTS: Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. CONCLUSIONS: Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications. PMID- 27273074 TI - The complement system, neuronal injury, and cognitive function in horizontally acquired HIV-infected youth. AB - The complement system (C1q/C3) is a key mediator of synaptic pruning during normal development. HIV inappropriately induces C1q and C3 production in the brain, and reduces neuronal complement inhibition. HIV may thus alter neural connectivity in the developing brain by excessively targeting synapses for elimination. The resultant pattern of neuronal injury may fundamentally alter neurodevelopmental and cognitive processes differentially across ages. This study aimed to (1) measure the association between the cerebrospinal fluid (CSF) complement factors (C1q/C3) and a marker of neuronal injury (NFL) in HIV+ subjects; (2) quantify the differences in CSF C1q/C3 between HIV+ youth and older adults; and (3) define the relationship between CSF C1q/C3 and cognitive impairment in each age group. We performed a retrospective cross-sectional study of 20 HIV+ 18-24-year-old youth and 20 HIV+ 40-46-year-old adults with varying levels of cognitive impairment enrolled in the CNS Antiretroviral Therapy Effects Research study. We quantified C3, C1q, and NFL by ELISA in paired CSF/plasma specimens. We found that CSF C1q correlates with NFL in all subjects not receiving antiretroviral therapy (n = 16, rho = 0.53, p = 0.035) when extreme NFL outliers were eliminated (n = 1). There was no difference in plasma/CSF C1q or C3 between older adults and youth. In 18-24-year-old youth, a nearly significant (p = 0.052) elevation of CSF C1q expression was observed in cognitively impaired subjects compared to cognitively normal subjects. Further investigation into the role of the CNS complement system in the neuropathogenesis of HIV is warranted and should be considered in a developmentally specific context. PMID- 27273075 TI - The flavivirus dengue induces hypertrophy of white matter astrocytes. AB - Flaviviruses, including Zika and dengue (DENV), pose a serious global threat to human health. Of the 50+ million humans infected with DENV annually, approximately 1-3 % progress to severe disease manifestations, dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Several factors are suspected to mediate the course of infection and pathogenesis of DENV infection. DHF and DSS are associated with vascular leakage and neurological sequelae. Our hypothesis was that altered astrocyte activation and morphology would alter the dynamics of the extracellular space and hence, neuronal and vascular function. We investigated the mechanisms of neuropathogenesis DENV infection in rhesus macaques. There were decreased numbers of GFAP immunopositive astrocytes per unit area, although those that remained had increased arbor length and complexity. This was combined with structural hypertrophy of white matter astrocytes in the absence of increased vascular leakage. Combined, these studies show how even low grade infection with DENV induces measurable changes within the parenchyma of infected individuals. PMID- 27273076 TI - Progressive multifocal leukoencephalopathy in a patient without apparent immunosuppression. AB - Progressive multifocal leukoencephalopathy (PML) is a viral demyelinating disease due to the reactivation of the JC virus (JCV), which usually occurs in the context of immunosuppression in HIV infection, malignancy, or in patients on disease modifying therapy for autoimmune diseases, such as multiple sclerosis (MS) and Crohn's disease. Notably, there is growing recognition that PML can occur in patients with transient immune dysfunction. Here, we present a case of a 55-year-old man without history of immunosuppression or evidence of ICL who was diagnosed with PML on brain biopsy. We will discuss the potential etiologies of mild and transient immunosuppression that can lead to PML with non-apparent immunosuppression. PMID- 27273077 TI - Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease. AB - The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p < 0.001), intercellular cell adhesion molecule-1 (ICAM-1) (p < 0.001), diabetes (p = 0.003), sex (p = 0.003), and history of cerebrovascular accidents (p = 0.021). In multivariate analyses for gait cadence, the significant independent predictors included high-sensitivity C-reactive protein (HsCRP) (p < 0.001), diabetes (p = 0.001), and hypertension (p = 0.001). In a multivariate regression model for gait stride length, the significant independent variables were HsCRP (p < 0.001), age (p < 0.001), ICAM-1 (p < 0.001), hypertension (p = 0.002), cellular reactive oxygen species production (p = 0.007), and sex (p = 0.008). Higher levels of circulating biomarkers of inflammation and endothelial cell oxidative stress were associated with slower gait speed, slower cadence, and shorter stride length in older symptomatic patients with PAD. Additionally, this profile of impaired gait was more evident in older patients, in women, and in those with diabetes, hypertension, and history of cerebrovascular accidents. PMID- 27273078 TI - Altered Crossover Distribution and Frequency in Spermatocytes of Infertile Men with Azoospermia. AB - During meiosis, homologous chromosomes pair to facilitate the exchange of DNA at crossover sites along the chromosomes. The frequency and distribution of crossover formation are tightly regulated to ensure the proper progression of meiosis. Using immunofluorescence techniques, our group and others have studied the meiotic proteins in spermatocytes of infertile men, showing that this population displays a reduced frequency of crossovers compared to fertile men. An insufficient number of crossovers is thought to promote chromosome missegregation, in which case the faulty cell may face meiotic arrest or contribute to the production of aneuploid sperm. Increasing evidence in model organisms has suggested that the distribution of crossovers may also be important for proper chromosome segregation. In normal males, crossovers are shown to be rare near centromeres and telomeres, while frequent in subtelomeric regions. Our study aims to characterize the crossover distribution in infertile men with non obstructive (NOA) and obstructive azoospermia (OA) along chromosomes 13, 18 and 21. Eight of the 16 NOA men and five of the 21 OA men in our study displayed reduced crossover frequency compared to control fertile men. Seven NOA men and nine OA men showed altered crossover distributions on at least one of the chromosome arms studied compared to controls. We found that although both NOA and OA men displayed altered crossover distributions, NOA men may be at a higher risk of suffering both altered crossover frequencies and distributions compared to OA men. Our data also suggests that infertile men display an increase in crossover formation in regions where they are normally inhibited, specifically near centromeres and telomeres. Finally, we demonstrated a decrease in crossovers near subtelomeres, as well as increased average crossover distance to telomeres in infertile men. As telomere-guided mechanisms are speculated to play a role in crossover formation in subtelomeres, future studies linking crossover distribution with telomere integrity and sperm aneuploidy may provide new insight into the mechanisms underlying male infertility. PMID- 27273079 TI - Noncovalent Substrate-Directed Enantioselective Heck Reactions: Synthesis of S- and P-Stereogenic Heterocycles. AB - S- and P-Stereogenic heterocycles were synthesized by a remarkably simple enantioselective Heck desymmetrization reaction based on the unprecedented noncovalent directing effect of S=O and P=O functionalities. Selected prochiral symmetric substrates were efficiently arylated using the recently disclosed chiral PyraBOx ligand under mild and open-flask reaction conditions. Several five membered aryl- sulfones, sulfoxides, and phosphine oxides were synthesized in good to excellent yields, in good to high diastereoselectivity, and enantiomeric ratios up to 98:2. Theoretical calculations also support the noncovalent directing effect of the S=O and P=O functionalities during the arylation process. PMID- 27273082 TI - Comparable responses of osteoblast lineage cells to microstructured hydrophilic titanium-zirconium and microstructured hydrophilic titanium. AB - OBJECTIVES: Although titanium (Ti) is commonly used for dental implants, Ti alloy materials are being developed to improve their physical material properties. Studies indicate that osteoblast differentiation and maturation of human mesenchymal stem cells (MSCs) and normal human osteoblasts (NHOsts) respond to microstructured Ti and titanium-aluminum-vanadium (Ti6Al4V) surfaces in a similar manner. The goal of this study was to determine whether this is the case for osteoblast lineage cells grown on microstructured TiZr surfaces and whether their response is affected by surface nanotexture and hydrophilicity. MATERIALS AND METHODS: Grade 4 Ti and TiZr (13-17% Zr) disks were modified by large grit sand blasting and acid-etching with storage in saline solution, resulting in a complex microstructured and hydrophilic surface corresponding to the commercially available implants SLActive(r) and Roxolid(r) SLActive(r) (Institut Straumann AG, Basel, Switzerland). The subsequent Ti modSLA and TiZr modSLA surfaces were characterized and osteogenic markers were measured. RESULTS: Evaluation of physical parameters revealed that the fabrication method was capable of inducing a microstructured and hydrophilic surface on both the Ti and TiZr disks. Overall, the surfaces were similar, but differences in nanostructure morphology/density and surface chemistry were detected. On Ti modSLA and TiZr modSLA, osteoblastic differentiation and maturation markers were enhanced in both MSCs and NHOsts, while inflammatory markers decreased compared with TCPS. CONCLUSIONS: These results indicate a similar positive cell response of MSCs and NHOsts when cultured on Ti modSLA and TiZr modSLA. Both surfaces were hydrophilic, indicating the importance of this property to osteoblast lineage cells. PMID- 27273085 TI - Direct effects dominate responses to climate perturbations in grassland plant communities. AB - Theory predicts that strong indirect effects of environmental change will impact communities when niche differences between competitors are small and variation in the direct effects experienced by competitors is large, but empirical tests are lacking. Here we estimate negative frequency dependence, a proxy for niche differences, and quantify the direct and indirect effects of climate change on each species. Consistent with theory, in four of five communities indirect effects are strongest for species showing weak negative frequency dependence. Indirect effects are also stronger in communities where there is greater variation in direct effects. Overall responses to climate perturbations are driven primarily by direct effects, suggesting that single species models may be adequate for forecasting the impacts of climate change in these communities. PMID- 27273086 TI - Thymic Germinal Centers and Corticosteroids in Myasthenia Gravis: an Immunopathological Study in 1035 Cases and a Critical Review. AB - The most common form of Myasthenia gravis (MG) is due to anti-acetylcholine receptor (AChR) antibodies and is frequently associated with thymic pathology. In this review, we discuss the immunopathological characteristics and molecular mechanisms of thymic follicular hyperplasia, the effects of corticosteroids on this thymic pathology, and the role of thymic epithelial cells (TEC), a key player in the inflammatory thymic mechanisms. This review is based not only on the literature data but also on thymic transcriptome results and analyses of pathological and immunological correlations in a vast cohort of 1035 MG patients without thymoma. We show that among patients presenting a thymic hyperplasia with germinal centers (GC), 80 % are females, indicating that thymic follicular hyperplasia is mainly a disease of women. The presence of anti-AChR antibodies is correlated with the degree of follicular hyperplasia, suggesting that the thymus is a source of anti-AChR antibodies. The degree of hyperplasia is not dependent upon the time from the onset, implying that either the antigen is chronically expressed and/or that the mechanisms of the resolution of the GC are not efficiently controlled. Glucocorticoids, a conventional therapy in MG, induce a significant reduction in the GC number, together with changes in the expression of chemokines and angiogenesis. These changes are likely related to the acetylation molecular process, overrepresented in corticosteroid-treated patients, and essential for gene regulation. Altogether, based on the pathological and molecular thymic abnormalities found in MG patients, this review provides some explanations for the benefit of thymectomy in early-onset MG patients. PMID- 27273087 TI - Complement, Kinins, and Hereditary Angioedema: Mechanisms of Plasma Instability when C1 Inhibitor is Absent. AB - Plasma of patients with types I and II hereditary angioedema is unstable if incubated in a plastic (i.e., inert) vessel at 37 degrees C manifested by progressively increasing formation of bradykinin. There is also a persistent low level of C4 in 95 % of patients even when they are symptomatic. These phenomena are due to the properties of the C1r subcomponent of C1, factor XII, and the bimolecular complex of prekallikrein with high molecular weight kininogen (HK). Purified C1r auto-activates in physiologic buffers, activates C1s, which in turn depletes C4. This occurs when C1 inhibitor is deficient. The complex of prekallikrein-HK acquires an inducible active site not present in prekallikrein which in Tris-type buffers cleaves HK stoichiometrically to release bradykinin, or in phosphate buffer auto-activates to generate kallikrein and bradykinin. Thus immunologic depletion of C1 inhibitor from factor XII-deficient plasma (phosphate is the natural buffer) auto-activates on incubation to release bradykinin. Normal C1 inhibitor prevents this from occurring. During attacks of angioedema, if factor XII auto-activates on surfaces, the initial factor XIIa formed converts prekallikrein to kallikrein, and kallikrein cleaves HK to release bradykinin. Kallikrein also rapidly activates most remaining factor XII to factor XIIa. Additional cleavages convert factor XIIa to factor XIIf and factor XIIf activates C1r enzymatically so that C4 levels approach zero, and C2 is depleted. There is also a possibility that kallikrein is generated first as a result of activation of the prekallikrein-HK complex by heat shock protein 90 released from endothelial cells, followed by kallikrein activation of factor XII. PMID- 27273089 TI - Bayesian Modeling of the Effects of Extreme Flooding and the Grazer Community on Algal Biomass Dynamics in a Monsoonal Taiwan Stream. AB - The effects of grazing and climate change on primary production have been studied widely, but seldom with mechanistic models. We used a Bayesian model to examine the effects of extreme weather and the invertebrate grazer community on epilithic algal biomass dynamics over 10 years (from January 2004 to August 2013). Algal biomass and the invertebrate grazer community were monitored in the upstream drainage of the Dajia River in Taiwan, where extreme floods have been becoming more frequent. The biomass of epilithic algae changed, both seasonally and annually, and extreme flooding changed the growth and resistance to flow detachment of the algae. Invertebrate grazing pressure changes with the structure of the invertebrate grazer community, which, in turn, is affected by the flow regime. Invertebrate grazer community structure and extreme flooding both affected the dynamics of epilithic algae, but in different ways. Awareness of the interactions between algal communities and grazers/abiotic factors can help with the design of future studies and could facilitate the development of management programs for stream ecosystems. PMID- 27273088 TI - Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol. AB - Few effective therapies exist for the treatment of neurodegenerative diseases that have been characterized as protein misfolding disorders. Upregulation of heat shock proteins (Hsps) mitigates against the accumulation of misfolded, aggregation-prone proteins and synaptic dysfunction, which is recognized as an early event in neurodegenerative diseases. Enhanced induction of a set of Hsps in differentiated human SH-SY5Y neuronal cells was observed following co-application of celastrol and arimoclomol, compared to their individual application. The dosages employed did not affect cell viability or neuronal process morphology. The induced Hsps included the little studied HSPA6 (Hsp70B'), a potentially neuroprotective protein that is present in the human genome but not in rat and mouse and hence is missing in current animal models of neurodegenerative disease. Enhanced induction of HSPA1A (Hsp70-1), DNAJB1 (Hsp40), HO-1 (Hsp32), and HSPB1 (Hsp27) was also observed. Celastrol activates heat shock transcription factor 1 (HSF1), the master regulator of Hsp gene transcription, and also exhibits potent anti-inflammatory and anti-oxidant activities. Arimoclomol is a co-activator that prolongs the binding of activated HSF1 to heat shock elements (HSEs) in the promoter regions of inducible Hsp genes. Elevated Hsp levels peaked at 10 to 12 h for HSPA6, HSPA1A, DNAJB1, and HO-1 and at 24 h for HSPB1. Co-application of celastrol and arimoclomol induced higher Hsp levels compared to heat shock paired with arimoclomol. The co-application strategy of celastrol and arimoclomol targets multiple neurodegenerative disease-associated pathologies including protein misfolding and protein aggregation, inflammatory and oxidative stress, and synaptic dysfunction. PMID- 27273090 TI - Resilience of Fungal Communities to Elevated CO2. AB - Soil filamentous fungi play a prominent role in regulating ecosystem functioning in terrestrial ecosystems. This necessitates understanding their responses to climate change drivers in order to predict how nutrient cycling and ecosystem services will be influenced in the future. Here, we provide a quantitative synthesis of ten studies on soil fungal community responses to elevated CO2. Many of these studies reported contradictory diversity responses. We identify the duration of the study as an influential parameter that determines the outcome of experimentation. Our analysis reconciles the existing globally distributed experiments on fungal community responses to elevated CO2 and provides a framework for comparing results of future CO2 enrichment studies. PMID- 27273091 TI - Retrieval of Brain Tumors by Adaptive Spatial Pooling and Fisher Vector Representation. AB - Content-based image retrieval (CBIR) techniques have currently gained increasing popularity in the medical field because they can use numerous and valuable archived images to support clinical decisions. In this paper, we concentrate on developing a CBIR system for retrieving brain tumors in T1-weighted contrast enhanced MRI images. Specifically, when the user roughly outlines the tumor region of a query image, brain tumor images in the database of the same pathological type are expected to be returned. We propose a novel feature extraction framework to improve the retrieval performance. The proposed framework consists of three steps. First, we augment the tumor region and use the augmented tumor region as the region of interest to incorporate informative contextual information. Second, the augmented tumor region is split into subregions by an adaptive spatial division method based on intensity orders; within each subregion, we extract raw image patches as local features. Third, we apply the Fisher kernel framework to aggregate the local features of each subregion into a respective single vector representation and concatenate these per-subregion vector representations to obtain an image-level signature. After feature extraction, a closed-form metric learning algorithm is applied to measure the similarity between the query image and database images. Extensive experiments are conducted on a large dataset of 3604 images with three types of brain tumors, namely, meningiomas, gliomas, and pituitary tumors. The mean average precision can reach 94.68%. Experimental results demonstrate the power of the proposed algorithm against some related state-of-the-art methods on the same dataset. PMID- 27273094 TI - BMP signaling turns up in fragile X syndrome: FMRP represses BMPR2. AB - Fragile X syndrome is the most common inherited form of intellectual disability and results from a loss of function of the translational repressor FMRP. In this issue of Science Signaling, Kashima et al find that FMRP binds to and represses a specific isoform of BMPR2, a type II bone morphogenetic protein (BMP) receptor. Reducing signaling through this BMP pathway reverses neuroanatomical defects observed in fragile X models. PMID- 27273092 TI - Cognitive deficits in first-degree relatives of bipolar patients: the use of homogeneous subgroups in the search of cognitive endophenotypes. AB - Previous studies have demonstrated impairments in attention, memory and executive functions in euthymic bipolar patients (BP) as well as their unaffected first degree relatives, albeit in an attenuated form. Subsequently, cognitive deficits are discussed as a possible endophenotype of bipolar disorder. However, recent studies showed that only a subgroup of BP shows cognitive impairments. The aim of the present study was to investigate cognitive functioning in relatives compared to BP, to find out if the differentiation in a cognitive deficit vs. non-deficit subgroup is valid for relatives of BP, too. Therefore, the performance of 27 unaffected relatives of BP, 27 euthymic BP and 27 HC were compared using a neuropsychological test battery. The results showed that BP exhibited a reduced psychomotor speed and deficits in working memory compared to relatives and HC. Relatives performed significantly slower (psychomotor speed) as compared to HC (p = 0.024); performance in the other test measures lie between BP and HC. Furthermore, a detailed evaluation of the data indicated that only subgroups of BP and relatives exhibited cognitive impairments in the implemented tests. However, the deficit and non-deficit groups did not differ in sociodemographic and clinical variables from each other, possibly due to the small sample size. In conclusion, our results suggest that reduced psychomotor speed could serve as a potential endophenotype for bipolar disorder which should be investigated along the developmental trajectory of this disorder, also to examine whether abnormalities therein precede onset of the first mood episode. Furthermore, the division of relatives into subgroups aids in the identification of stable trait markers and high-risk bipolar groups and could enable early prevention strategies. As to that more research using distinct and homogeneous subgroups is necessary. PMID- 27273093 TI - Training programmes for family caregivers of people with dementia living at home: integrative review. AB - AIMS AND OBJECTIVES: To establish primary features of training programmes designed to assist family caregivers of people with dementia living at home and to propose a model programme based on literature findings. BACKGROUND: Due to dementia's distinctive progression, there is a widely felt need to train family members who undertake the responsibility of caring for relatives diagnosed with this condition to provide positive care, particularly during the early and middle stages of the disease. DESIGN: Integrative review. METHODS: Literature reviews were carried out in the Pubmed, CINAHL, Mediclatina and Medline databases, using the following describers: training programme, family caregivers, dementia and aged. Such searches encompassed publications between 2004-2014, together with eight articles for review due to their positive identification with the inclusion criteria. Relevant results were extracted, the subsequent analysis performed and the presentation carried out in a descriptive manner. RESULTS: The prevailing length of a training programme for a family caregiver of people with dementia is of six sessions over a six-week period, with one weekly session load, and an average duration of 100 minutes each. Methodologies most commonly used include discussion, problem-solving models as well as skills and strategies training. The themes discussed comprehend caring for the individual with dementia, information about the illness and the use of health and community resources. Regarding the assessment of the family caregiver, the most widely used instruments are demographic assessment questionnaires, self-efficiency and caregiver's burnout scales, as well as depression and quality of life measures. Three assessment instances of family caregivers' needs during the training programme are commonly encountered: initial, final and follow-up. CONCLUSIONS: This review has identified a set of features transversal to training programmes for family members who undertake the care for individuals with dementia living at home, which will bolster the construction and validation of other programmes in the area. More studies about such programmes need to be implemented, particularly engaged in their conceptual and experimental validation. RELEVANCE TO CLINICAL PRACTICE: The results of this review assist nurses by increasing their awareness of the basic assumptions supporting training programmes for family members responsible for individuals with dementia living at home and subsequently enforce them during their interventions with such population. PMID- 27273095 TI - Science Signaling Podcast for 7 June 2016: Modeling signal integration. AB - This Podcast features an interview with Kevin Janes, senior author of a Research Article that appears in the 7 June 2016 issue of Science Signaling, about a statistical modeling method that can extract useful information from complex data sets. Cells exist in very complex environments. They are constantly exposed to growth factors, hormones, nutrients, and many other factors that influence cellular behavior. When cells integrate information from multiple stimuli, the resulting output does not necessarily reflect a simple additive effect of the responses to each individual stimulus. Chitforoushzadeh et al employed a statistical modeling approach that maintained the multidimensional nature of the data to analyze the responses of colonic epithelial cells to various combinations of the proinflammatory cytokine TNF, the growth factor EGF, and insulin. As the model predicted, experiments confirmed that insulin suppressed TNF-induced proinflammatory signaling through a mechanism that involved the transcription factor GATA6.Listen to Podcast. PMID- 27273096 TI - Augmented noncanonical BMP type II receptor signaling mediates the synaptic abnormality of fragile X syndrome. AB - Epigenetic silencing of fragile X mental retardation 1 (FMR1) causes fragile X syndrome (FXS), a common inherited form of intellectual disability and autism. FXS correlates with abnormal synapse and dendritic spine development, but the molecular link between the absence of the FMR1 product FMRP, an RNA binding protein, and the neuropathology is unclear. We found that the messenger RNA encoding bone morphogenetic protein type II receptor (BMPR2) is a target of FMRP. Depletion of FMRP increased BMPR2 abundance, especially that of the full-length isoform that bound and activated LIM domain kinase 1 (LIMK1), a component of the noncanonical BMP signal transduction pathway that stimulates actin reorganization to promote neurite outgrowth and synapse formation. Heterozygosity for BMPR2 rescued the morphological abnormalities in neurons both in Drosophila and in mouse models of FXS, as did the postnatal pharmacological inhibition of LIMK1 activity. Compared with postmortem prefrontal cortex tissue from healthy subjects, the amount of full-length BMPR2 and of a marker of LIMK1 activity was increased in this brain region from FXS patients. These findings suggest that increased BMPR2 signal transduction is linked to FXS and that the BMPR2-LIMK1 pathway is a putative therapeutic target in patients with FXS and possibly other forms of autism. PMID- 27273099 TI - An updated review of Parkinson's disease genetics and clinicopathological correlations. AB - Knowledge regarding the pathophysiological basis of Parkinson's disease (PD) has been greatly expanded over the past two decades, with extraordinary contributions from the field of genetics. However, genetic classifications became complex, difficult to follow, and at times misleading, by placing well-established monogenic forms of the disease along with others associated with risk loci, often ill characterized. The present paper summarizes the genetic, clinical, and neuropathological findings of the currently described monogenic forms of PD and also approaches the progress made in determining genetic risk factors for PD. Furthermore, the text incorporates the data into a recently proposed classification system that will hopefully bring a "user-friendly" approach to this issue. This paper also highlights a number of inconsistencies regarding classification of PD as a single, unique clinicopathological entity-in fact, in order to achieve the development of truly innovative therapies, PD should probably be regarded clinically as a "Parkinson's disease cluster", instead of a single disease. In the future, we hope that an in-depth and groundbreaking understanding of PD will allow the development of truly disease-modifying therapies that will target the molecular processes responsible for the cascade of pathological events underlying each form of PD. PMID- 27273098 TI - Sestrin regulation of TORC1: Is Sestrin a leucine sensor? AB - Sestrins are highly conserved, stress-inducible proteins that inhibit target of rapamycin complex 1 (TORC1) signaling. After their transcriptional induction, both vertebrate and invertebrate Sestrins turn on the adenosine monophosphate (AMP)-activated protein kinase (AMPK), which activates the tuberous sclerosis complex (TSC), a key inhibitor of TORC1 activation. However, Sestrin overexpression, on occasion, can result in TORC1 inhibition even in AMPK deficient cells. This effect has been attributed to Sestrin's ability to bind the TORC1-regulating GATOR2 protein complex, which was postulated to control trafficking of TORC1 to lysosomes. How the binding of Sestrins to GATOR2 is regulated and how it contributes to TORC1 inhibition are unknown. New findings suggest that the amino acid leucine specifically disrupts the association of Sestrin2 with GATOR2, thus explaining how leucine and related amino acids stimulate TORC1 activity. We discuss whether and how these findings fit what has already been learned about Sestrin-mediated TORC1 inhibition from genetic studies conducted in fruit flies and mammals. PMID- 27273100 TI - 60 YEARS OF POMC: POMC: the consummate peptide hormone precursor. PMID- 27273097 TI - TNF-insulin crosstalk at the transcription factor GATA6 is revealed by a model that links signaling and transcriptomic data tensors. AB - Signal transduction networks coordinate transcriptional programs activated by diverse extracellular stimuli, such as growth factors and cytokines. Cells receive multiple stimuli simultaneously, and mapping how activation of the integrated signaling network affects gene expression is a challenge. We stimulated colon adenocarcinoma cells with various combinations of the cytokine tumor necrosis factor (TNF) and the growth factors insulin and epidermal growth factor (EGF) to investigate signal integration and transcriptional crosstalk. We quantitatively linked the proteomic and transcriptomic data sets by implementing a structured computational approach called tensor partial least squares regression. This statistical model accurately predicted transcriptional signatures from signaling arising from single and combined stimuli and also predicted time-dependent contributions of signaling events. Specifically, the model predicted that an early-phase, AKT-associated signal downstream of insulin repressed a set of transcripts induced by TNF. Through bioinformatics and cell based experiments, we identified the AKT-repressed signal as glycogen synthase kinase 3 (GSK3)-catalyzed phosphorylation of Ser(37) on the long form of the transcription factor GATA6. Phosphorylation of GATA6 on Ser(37) promoted its degradation, thereby preventing GATA6 from repressing transcripts that are induced by TNF and attenuated by insulin. Our analysis showed that predictive tensor modeling of proteomic and transcriptomic data sets can uncover pathway crosstalk that produces specific patterns of gene expression in cells receiving multiple stimuli. PMID- 27273101 TI - Gordon Gregory OAM: An appreciation. PMID- 27273102 TI - Food security in Australia. PMID- 27273103 TI - Granulocyte infusion: benefit beyond neutrophils? PMID- 27273105 TI - Need Continuing Education Contact Hours? Register for the AANP 2016 National Conference. PMID- 27273104 TI - The Human Antimicrobial Protein Bactericidal/Permeability-Increasing Protein (BPI) Inhibits the Infectivity of Influenza A Virus. AB - In addition to their well-known antibacterial activity some antimicrobial peptides and proteins (AMPs) display also antiviral effects. A 27 aa peptide from the N-terminal part of human bactericidal/permeability-increasing protein (BPI) previously shown to harbour antibacterial activity inhibits the infectivity of multiple Influenza A virus strains (H1N1, H3N2 and H5N1) the causing agent of the Influenza pneumonia. In contrast, the homologous murine BPI-peptide did not show activity against Influenza A virus. In addition human BPI-peptide inhibits the activation of immune cells mediated by Influenza A virus. By changing the human BPI-peptide to the sequence of the mouse homologous peptide the antiviral activity was completely abolished. Furthermore, the human BPI-peptide also inhibited the pathogenicity of the Vesicular Stomatitis Virus but failed to interfere with HIV and measles virus. Electron microscopy indicate that the human BPI-peptide interferes with the virus envelope and at high concentrations was able to destroy the particles completely. PMID- 27273106 TI - Post Publication Peer Review: Is it Coming to Your Nursing Journal? PMID- 27273107 TI - Assessing current genetic status of the Hainan gibbon using historical and demographic baselines: implications for conservation management of species of extreme rarity. AB - Evidence-based conservation planning is crucial for informing management decisions for species of extreme rarity, but collection of robust data on genetic status or other parameters can be extremely challenging for such species. The Hainan gibbon, possibly the world's rarest mammal, consists of a single population of ~25 individuals restricted to one protected area on Hainan Island, China, and has persisted for over 30 years at exceptionally low population size. Analysis of genotypes at 11 microsatellite loci from faecal samples for 36% of the current global population and tissue samples from 62% of existing historical museum specimens demonstrates limited current genetic diversity (Na = 2.27, Ar = 2.24, He = 0.43); diversity has declined since the 19th century and even further within the last 30 years, representing declines of ~30% from historical levels (Na = 3.36, Ar = 3.29, He = 0.63). Significant differentiation is seen between current and historical samples (FST = 0.156, P = 0.0315), and the current population exhibits extremely small Ne (current Ne = 2.16). There is evidence for both a recent population bottleneck and an earlier bottleneck, with population size already reasonably low by the late 19th century (historical Ne = 1162.96). Individuals in the current population are related at the level of half- to full-siblings between social groups, and full-siblings or parent-offspring within a social group, suggesting that inbreeding is likely to increase in the future. The species' current reduced genetic diversity must be considered during conservation planning, particularly for expectations of likely population recovery, indicating that intensive, carefully planned management is essential. PMID- 27273108 TI - Shakespeare's understanding of human afflictions. PMID- 27273109 TI - [Risk management in anesthesia and critical care medicine]. AB - Throughout its history, anesthesia and critical care medicine has experienced vast improvements to increase patient safety. Consequently, anesthesia has never been performed on such a high level as it is being performed today. As a result, we do not always fully perceive the risks involved in our daily activity. A survey performed in Swiss hospitals identified a total of 169 hot spots which endanger patient safety. It turned out that there is a complex variety of possible errors that can only be tackled through consistent implementation of a safety culture. The key elements to reduce complications are continuing staff education, algorithms and standard operating procedures (SOP), working according to the principles of crisis resource management (CRM) and last but not least the continuous work-up of mistakes identified by critical incident reporting systems. PMID- 27273110 TI - [Inhalation and intravenous anesthesia in pediatric patients]. AB - Inhalation as well as total intravenous anesthesia have both advantages and disadvantages. The pros of an inhalation technique are mask induction without the initial need for intravenous access and precise dosing; the pros of an intravenous technique are postoperative quiet recovery and a low incidence of vomiting. With both techniques the aim is to reach a certain, most often constant effect site concentration, which after a short latent period equals the blood concentration. Initially, with both techniques a higher dosing is required to wash in the compound. An inhalational technique allows the end-tidal concentration to be measured and dosing to be adjusted. Dosing of intravenous anesthetics is based on assumptions. For neonates and young infants an inhalation technique is often preferred because of metabolic immaturity and the resulting difficulties of dosing, whereas older children can often profit from a quiet awakening and a reduced incidence of vomiting. The increased availability of syringe pumps with incorporated algorithms as well as of electroencephalograph (EEG)-based monitoring systems will further promote the popularity of total intravenous anesthesia. PMID- 27273111 TI - Lower bone turnover and relative bone deficits in men with metabolic syndrome: a matter of insulin sensitivity? The European Male Ageing Study. AB - : We examined cross-sectional associations of metabolic syndrome and its components with male bone turnover, density and structure. Greater bone mass in men with metabolic syndrome was related to their greater body mass, whereas hyperglycaemia, hypertriglyceridaemia or impaired insulin sensitivity were associated with lower bone turnover and relative bone mass deficits. INTRODUCTION: Metabolic syndrome (MetS) has been associated with lower bone turnover and relative bone mass or strength deficits (i.e. not proportionate to body mass index, BMI), but the relative contributions of MetS components related to insulin sensitivity or obesity to male bone health remain unclear. METHODS: We determined cross-sectional associations of MetS, its components and insulin sensitivity (by homeostatic model assessment-insulin sensitivity (HOMA-S)) using linear regression models adjusted for age, centre, smoking, alcohol, and BMI. Bone turnover markers and heel broadband ultrasound attenuation (BUA) were measured in 3129 men aged 40-79. Two centres measured total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD, n = 527) and performed radius peripheral quantitative computed tomography (pQCT, n = 595). RESULTS: MetS was present in 975 men (31.2 %). Men with MetS had lower beta C-terminal cross-linked telopeptide (beta-CTX), N-terminal propeptide of type I procollagen (PINP) and osteocalcin (P < 0.0001) and higher total hip, femoral neck, and lumbar spine aBMD (P <= 0.03). Among MetS components, only hypertriglyceridaemia and hyperglycaemia were independently associated with PINP and beta-CTX. Hyperglycaemia was negatively associated with BUA, hypertriglyceridaemia with hip aBMD and radius cross-sectional area (CSA) and stress-strain index. HOMA-S was similarly associated with PINP and beta-CTX, BUA, and radius CSA in BMI-adjusted models. CONCLUSIONS: Men with MetS have higher aBMD in association with their greater body mass, while their lower bone turnover and relative deficits in heel BUA and radius CSA are mainly related to correlates of insulin sensitivity. Our findings support the hypothesis that underlying metabolic complications may be involved in the bone's failure to adapt to increasing bodily loads in men with MetS. PMID- 27273114 TI - Nurses and midwives need health promotion as much as their patients. PMID- 27273112 TI - Comparative efficacy of bisphosphonates in short-term fracture prevention for primary osteoporosis: a systematic review with network meta-analyses. AB - : Our network meta-analyses compared the efficacy of different bisphosphonates preventing fractures for primary osteoporosis. By including 36 studies, we found that zoledronic acid seemed the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture, and alendronate or zoledronic acid seemed the most effective in preventing hip fracture. INTRODUCTION: This study was conducted in order to analyze the available evidence on the efficacy of bisphosphonates for preventing fractures. METHODS: We considered randomized trials comparing any bisphosphonate with other bisphosphonate or placebo. We searched Cochrane Library, Embase, and PubMed and manually searched reference list of relevant articles. Pairwise and network meta-analyses were performed. The primary outcome is vertebral fracture. Secondary outcomes include nonvertebral fracture, hip fracture, wrist fracture, and any fracture. RESULTS: Thirty-six studies were included. Significant difference was found between bisphosphonates for vertebral fracture and nonvertebral fracture (P < 0.0001 and P = 0.04, respectively). Compared with placebo, alendronate, clodronate, ibandronate, minodronate, pamidronate, risedronate, and zoledronic acid significantly prevented vertebral fracture. Zoledronic acid significantly reduced the risk of vertebral fracture, compared with alendronate, clodronate, etidronate, ibandronate, risedronate, and tiludronate (0.65 (0.46, 0.91), 0.53 (0.33, 0.86), 0.45 (0.27, 0.74), 0.52 (0.36, 0.75), 0.59 (0.42, 0.83), and 0.31 (0.21, 0.48), respectively). Compared with etidronate, clodronate and zoledronic acid significantly prevented nonvertebral fracture. Compared with alendronate, zoledronic acid significantly prevented any fracture. The possibility rankings showed that zoledronic ranked first in preventing vertebral fracture, hip fracture, and any fracture, and pamidronate ranked first in preventing nonvertebral fracture and wrist fracture. In the sensitivity analyses, zoledronic acid ranked first in preventing nonvertebral fracture, and alendronate ranked first in preventing hip fracture and wrist fracture. CONCLUSION: Zoledronic acid seemed the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture, and alendronate or zoledronic acid seemed the most effective in preventing hip fracture. Uncertainty still remains and future studies are needed to accurately evaluate the comparative efficacy of bisphosphonates. PMID- 27273113 TI - Glucocorticoid exposure and fracture risk in patients with new-onset rheumatoid arthritis. AB - : Retrospective claims analysis indicated that high levels of daily and cumulative doses of systemic glucocorticoids were associated with elevated fracture risk in a large cohort of new RA patients under age 65. Heightened risk began to decline within months of discontinuation. Findings were similar among patients age <50 years. INTRODUCTION: We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new onset rheumatoid arthritis (RA). METHODS: Using administrative data, we identified 42,127 RA patients diagnosed January 1, 2005-December 31, 2012, age 18 64 years, with benefits coverage for >=12 months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. RESULTS: Most patients (85 %) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74 % female; mean age 49.7 and 48.8 years); 1 % had prior fracture. Fracture IRs (95 % confidence intervals) were 5 to 9 per 1000 person-years at doses <15 mg/day, 16.0 (11.0, 22.6) at doses >=15 mg/day, and 13.4 (10.7, 16.7) at cumulative doses >=5400 mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0 mg/day current daily dose and <675 mg cumulative dose, respectively. Fracture risk was 29 % lower at 60-182 days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12 months. Findings were similar among patients age <50 years. CONCLUSIONS: Among younger, new-onset RA patients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12 months post-discontinuation. PMID- 27273116 TI - Shaping and enforcing coordination spheres: probing the ability of tripodal ligands to favour trigonal prismatic geometry. AB - We report two tripodal frameworks, mono(2,2'-bipyrid-6-yl)bis(2-pyridyl)methanol () and bis(2,2'-bipyrid-6-yl)mono(2-pyridyl)methanol () which have one and two bipyridyl arms, respectively. Both ligands form complexes with the first row transition metals. Both ligands appear to overcome the steric strain involved in twisting the ligand to produce an octahedral complex and the solid state structures in general show more octahedral character than complexes of the related ligand, tris(2,2'-bipyrid-6-yl)methanol (). Continuous Shape Mapping (CShM) calculations based on crystallographic data reveal that is incapable of enforcing a trigonal prismatic (TP) co-ordination geometry in the solid state, surprisingly even upon co-ordination to metals with no stereochemical preference such as cadmium (S(TP) = 7.15 and S(Oh) = 3.95). However, ligand clearly maintains an ability to enforce a trigonal prismatic conformation which is demonstrated in the crystal structures of the Mn(II) and Cd(II) complexes (S(TP) = 0.75 and 1.09, respectively). While maintains near-TP configurations in the presence of metal ions with strong octahedral preferences, distorts towards predominantly octahedral co-ordination geometries, increasing in the order Co(II) < Ni(II) < Fe(II) and no trigonal prismatic structures. PMID- 27273117 TI - Dr. Charles Leslie MacAdams. PMID- 27273115 TI - Biomechanical deformable image registration of longitudinal lung CT images using vessel information. AB - Spatial correlation of lung tissue across longitudinal images, as the patient responds to treatment, is a critical step in adaptive radiotherapy. The goal of this work is to expand a biomechanical model-based deformable registration algorithm (Morfeus) to achieve accurate registration in the presence of significant anatomical changes. Six lung cancer patients previously treated with conventionally fractionated radiotherapy were retrospectively evaluated. Exhale CT scans were obtained at treatment planning and following three weeks of treatment. For each patient, the planning CT was registered to the follow-up CT using Morfeus, a biomechanical model-based deformable registration algorithm. To model the complex response of the lung, an extension to Morfeus has been developed: an initial deformation was estimated with Morfeus consisting of boundary conditions on the chest wall and incorporating a sliding interface with the lungs. It was hypothesized that the addition of boundary conditions based on vessel tree matching would provide a robust reduction of the residual registration error. To achieve this, the vessel trees were segmented on the two images by thresholding a vesselness image based on the Hessian matrix's eigenvalues. For each point on the reference vessel tree centerline, the displacement vector was estimated by applying a variant of the Demons registration algorithm between the planning CT and the deformed follow-up CT. An expert independently identified corresponding landmarks well distributed in the lung to compute target registration errors (TRE). The TRE was: [Formula: see text], [Formula: see text] and [Formula: see text] mm after rigid registration, Morfeus and Morfeus with boundary conditions on the vessel tree, respectively. In conclusion, the addition of boundary conditions on the vessels significantly improved the accuracy in modeling the response of the lung and tumor over the course of radiotherapy. Minimizing and modeling these geometrical uncertainties will enable future plan adaptation strategies. PMID- 27273118 TI - Acute exacerbation of hepatitis C in hepatocellular carcinoma patients receiving chemotherapy. AB - Acute hepatitis C exacerbations can occur in cancer patients carrying hepatitis C virus (HCV) when receiving systemic chemotherapy. However, clinical studies evaluating these complications remain rare due to the lack of clinically proven effective and tolerable anti-HCV treatments at late cancer stages. Furthermore, no data were available regarding hepatitis C exacerbation in advanced hepatocellular carcinoma (HCC) patients receiving chemotherapy. To address this issue, 48 patients with HCV-related advanced HCC, who underwent systemic chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone from 2008 to 2014 were analyzed. Nine patients developed acute hepatitis exacerbations defined by HCV-RNA elevation >=10-fold and alanine transaminase (ALT) elevation >=5-fold of the upper normal limit. Six were genotype 1b and 3 were genotype 2. Three patterns of clinical courses were observed including single episode of exacerbation (n = 5), fluctuated flares (n = 3), and delayed exacerbation (n = 1). Hepatic failure developed in five patients. Patients with acute exacerbations were less likely to have pretreatment ascites (11.1% vs. 53.8%; P = 0.028) and displayed a lower baseline ALT (44.1 +/- 28.5 U/L vs. 72.6 +/- 19.2 U/L; P = 0.007). Paradoxically, despite a high risk of hepatic failure, occurrence of hepatitis C exacerbation was associated with a favorable overall survival (P = 0.027; 22.8 vs. 5.4 months). In conclusion, hepatitis C exacerbation can occur in HCC patients receiving chemotherapy, leading to liver failure. However, the flare was associated with a better overall survival, possibly due to its association with a better baseline liver function. J. Med. Virol. 89:153-160, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27273119 TI - Indomethacin induces differential effects on in vitro endochondral ossification depending on the chondrocyte's differentiation stage. AB - Heterotopic ossification (HO) is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. Heterotopic ossifications are described to develop via endochondral ossification and standard treatment is administration of indomethacin. It is currently unknown how indomethacin influences heterotopic ossification on a molecular level; therefore, we aimed to determine whether indomethacin might influence heterotopic ossification via impairing the chondrogenic phase of endochondral ossification. Progenitor cell models differentiating in the chondrogenic lineage (ATDC5, primary human bone marrow stem cells and ex vivo periosteal agarose cultures) were treated with increasing concentrations of indomethacin and a decrease in gene- and protein expression of chondrogenic and hypertrophic markers (measured by RT-qPCR and immunoblotting) as well as decreased glycosamino-glycan content (by alcian blue histochemistry) was observed. Even when hypertrophic differentiation was provoked, the addition of indomethacin resulted in decreased hypertrophic marker expression. Interestingly, when mature chondrocytes were treated with indomethacin, a clear increase in collagen type 2 expression was observed. Similarly, when ATDC5 cells and bone marrow stem cells were pre differentiated to obtain a chondrocyte phenotype and indomethacin was added from this time point onward, low concentrations of indomethacin also resulted in increased chondrogenic differentiation. Indomethacin induces differential effects on in vitro endochondral ossification, depending on the chondrocyte's differentiation stage, with complete inhibition of chondrogenic differentiation as the most pronounced action. This observation may provide a rational behind the elusive mode of action of indomethacin in the treatment of heterotopic ossifications. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:847-857, 2017. PMID- 27273120 TI - Increased variance in temperature and lag effects alter phenological responses to rapid warming in a subarctic plant community. AB - Summer temperature on the Cape Churchill Peninsula (Manitoba, Canada) has increased rapidly over the past 75 years, and flowering phenology of the plant community is advanced in years with warmer temperatures (higher cumulative growing degree days). Despite this, there has been no overall shift in flowering phenology over this period. However, climate change has also resulted in increased interannual variation in temperature; if relationships between phenology and temperature are not linear, an increase in temperature variance may interact with an increase in the mean to alter how community phenology changes over time. In our system, the relationship between phenology and temperature was log-linear, resulting in a steeper slope at the cold end of the temperature spectrum than at the warm end. Because below-average temperatures had a greater impact on phenology than above-average temperatures, the long-term advance in phenology was reduced. In addition, flowering phenology in a given year was delayed if summer temperatures were high the previous year or 2 years earlier (lag effects), further reducing the expected advance over time. Phenology of early-flowering plants was negatively affected only by temperatures in the previous year, and that of late-flowering plants primarily by temperatures 2 years earlier. Subarctic plants develop leaf primordia one or more years prior to flowering (preformation); these results suggest that temperature affects the development of flower primordia during this preformation period. Together, increased variance in temperature and lag effects interacted with a changing mean to reduce the expected phenological advance by 94%, a magnitude large enough to account for our inability to detect a significant advance over time. We conclude that changes in temperature variability and lag effects can alter trends in plant responses to a warming climate and that predictions for changes in plant phenology under future warming scenarios should incorporate such effects. PMID- 27273121 TI - Antioxidant and anti-inflammatory potential of pomegranate rind extract to ameliorate cisplatin-induced acute kidney injury. AB - Cisplatin is a chemotherapeutic agent, but the therapeutic utility is limited due to its dose dependent nephrotoxicity. The aim of the present study was to evaluate the nephroprotective effect of pomegranate in cisplatin-induced acute kidney injury. Wistar rats were allocated into six groups as follows: the normal control, cisplatin-induced, pomegranate rind extract treatment (50, 100 and 200 mg kg(-1)) and pomegranate rind extract per se group. All the experimental test drugs/vehicle were administered orally for a period of ten days. Intraperitoneal injection of cisplatin (8 mg kg(-1)) was administered on day 7 to all the groups except the normal control and pomegranate per se group. On day 10, cisplatin resulted in significant nephrotoxicity in Wistar rats with a drastic elevation of serum creatinine and BUN, a decline in the concentrations of GSH, MDA and superoxide dismutase (SOD), and an elevation in the TNF-alpha level in renal tissues. Pathological changes in renal tissues were examined by histopathology and dysfunction in mitochondria and proximal tubule cells was detected by transmission electron microscopy. The rate of apoptosis and the expression of caspase-3, Il-1beta and IL-6 in rat renal tissues were detected by immunohistochemistry. The administration of pomegranate at a dose of 200 mg per kg body weight significantly (p < 0.001) ameliorates increased serum creatinine and BUN. In parallel to this, pomegranate also exhibits anti-apoptotic activity through the reduction of active caspase-3 expression in kidneys. Additionally, in silico studies also confirmed a renoprotective effect of pomegranate. The above findings suggest that pomegranate can be used as a dietary supplement in the treatment of cisplatin-induced kidney injury by reducing apoptosis, oxidative stress and inflammation. PMID- 27273122 TI - Applications of the CRISPR/Cas9 system in murine cancer modeling. AB - Advanced biological technologies allowing for genetic manipulation of the genome are increasingly being used to unravel the molecular pathogenesis of human diseases. The clustered regulatory interspaced short palindromic repeat/CRISPR associated protein (CRISPR/Cas) technology started a revolution of this field owing to its flexibility and relative ease of use. Recently, application of the CRISPR/Cas9 system has been extended to in vivo approaches, leveraging its potential for human disease modeling. Particularly in oncological research, where genetic defects in somatic cells are tightly linked to etiology and pathological phenotypes, the CRISPR/Cas technology is being used to recapitulate various types of genetic aberrations. Here we review murine cancer models that have been developed via combining the CRISPR/Cas9 technology with in vivo somatic gene transfer approaches. Exploiting these methodological advances will further accelerate detailed investigations of tumor etiology and treatment. PMID- 27273123 TI - Ship in a breakable bottle: fluoride-induced release of an organic molecule from a Pr(iii)-linked molecular cage. AB - A 3-dimensional networked molecular cage, , has been synthesized. This macrocycle based framework was prepared from a solvothermal reaction involving a flexible organic building block, calix[4]pyrrole dibenzoic acid (H2), and Pr(NO3)3.6H2O. A unique feature of is that it retains free calix[4]pyrrole molecules in the framework pores. Treatment with a fluoride anion source serves to destroy the network and allows release of the organic guest. The net result is a 'molecular ship' in a 'breakable bottle'. PMID- 27273124 TI - Antioxidant Bioactive Compounds Changes in Fruit of Quince Genotypes Over Cold Storage. AB - Quince fruit has many benefits to human health and is excellent source of bioactive compounds. The fruit of 15 quince genotypes stored at 2 degrees C for 5 mo to study fruit quality changes during cold storage. Fruit were sampled monthly and stored at 20 degrees C for 24 h. Fruit ascorbic acid (AA), total phenol (TP), and total flavonoid (TF) concentrations, total antioxidant activity (TAA), flesh browning (FB) incidence, polyphenol oxidase (PPO), peroxidase (POX), and superoxide dismutase (SOD) activities were measured during storage. A high variation in bioactive compounds was observed across genotypes. The range of 26.8 to 44.4 mg/100 g FW for AA, 86.7% to 98.2% for TAA, 157.7 to 380.7 mg GAE 100(-1) g FW for TP, and 5.3 to 10.7 mg/100 g FW for TF were observed across genotypes at harvest time. The overall AA, TAA, TP, TF, and SOD decreased while PPO and POX increased during storage. FB was first observed after 4 mo and increased thereafter while the FB index was different across genotypes. Higher bioactive content may prevent or reduce FB index so that a negative correlation was found between FB and AA, TAA, TP, TF, and SOD. PMID- 27273127 TI - Correlated versus uncorrelated frailty Cox models: A comparison of different estimation procedures. AB - In many studies in medicine, including clinical trials and epidemiological investigations, data are clustered into groups such as health centers or herds in veterinary medicine. Such data are usually analyzed by hierarchical regression models to account for possible variation between groups. When such variation is large, it is of potential interest to explore whether additionally the effect of a within-group predictor varies between groups. In survival analysis, this may be investigated by including two frailty terms at group level in a Cox proportional hazards model. Several estimation methods have been proposed to estimate this type of frailty Cox models. We review four of these methods, apply them to real data from veterinary medicine, and compare them using a simulation study. PMID- 27273129 TI - A case of penile basal cell carcinoma reconstructed by scrotal myofasciocutaneous flap. AB - Basal cell carcinoma is the most common cutaneous malignant tumor and usually arises from the facial skin and is diagnosed as the solid tumor. However, rarely it arises from genital skin and/or proceeds with ulcerative manner. We report a case of male basal cell carcinoma arising from penile base, which showed urinary disturbance. Tumor resection including total penectomy and skin resection was performed then scrotal myofasciocutaneous flap was used to cover the defect. Scrotal myofasciocutaneous flap was useful for covering the defect in the genital lesion. Moreover, this simple closure was helpful for early postoperative ambulation especially for aged male patients. PMID- 27273128 TI - Reversing diet-induced metabolic dysregulation by diet switching leads to altered hepatic de novo lipogenesis and glycerolipid synthesis. AB - In humans, low-energy diets rapidly reduce hepatic fat and improve/normalise glycemic control. Due to difficulties in obtaining human liver, little is known about changes to the lipid species and pathway fluxes that occur under these conditions. Using a combination of stable isotope, and targeted metabolomic approaches we investigated the acute (7-9 days) hepatic effects of switching high fat high-sucrose diet (HFD) fed obese mice back to a chow diet. Upon the switch, energy intake was reduced, resulting in reductions of fat mass and hepatic triacyl- and diacylglycerol. However, these parameters were still elevated compared to chow fed mice, thus representing an intermediate phenotype. Nonetheless, glucose intolerance and hyperinsulinemia were completely normalized. The diet reversal resulted in marked reductions in hepatic de novo lipogenesis when compared to the chow and HFD groups. Compared with HFD, glycerolipid synthesis was reduced in the reversal animals, however it remained elevated above that of chow controls, indicating that despite experiencing a net loss in lipid stores, the liver was still actively esterifying available fatty acids at rates higher than that in chow control mice. This effect likely promotes the re esterification of excess free fatty acids released from the breakdown of adipose depots during the weight loss period. PMID- 27273130 TI - Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy. AB - Current clinical algorithms are unable to precisely predict which colorectal cancer patients would benefit from adjuvant chemotherapy, and there is a need for novel biomarkers to improve the selection of patients. The metastasis-promoting protein S100A4 predicts poor outcome in colorectal cancer, but whether it could be used to guide clinical decision making remains to be resolved. S100A4 expression was analyzed by immunohistochemistry in primary colorectal carcinomas from a consecutively collected, population-representative cohort and a randomized phase III study on adjuvant 5-fluorouracil/levamisole. Sensitivity to treatment with 5-fluorouracil in S100A4 knockdown cells was investigated using 2D and 3D cell culture assays. Strong nuclear expression of S100A4 was detected in 19% and 23% of the tumors in the two study cohorts, respectively. In both cohorts, nuclear immunoreactivity was associated with reduced relapse-free (P < 0.001 and P = 0.010) and overall survival (P = 0.046 and P = 0.006) in univariate analysis. In multivariate analysis, nuclear S100A4 was a predictor of poor relapse-free survival in the consecutive series (P = 0.002; HR 1.9), but not in the randomized study. Sensitivity to treatment with 5-fluorouracil was not affected by S100A4 expression in in vitro cell culture assays, and there was no indication from subgroup analyses in the randomized study that S100A4 expression was associated with increased benefit of adjuvant treatment with 5-fluorouracil/levamisole. The present study confirms that nuclear S100A4 expression is a negative prognostic biomarker in colorectal cancer, but the clinical utility in selection of patients for adjuvant fluoropyrimidine-based chemotherapy is limited. PMID- 27273131 TI - Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing. AB - The sensitivity of testing BRCA1 and BRCA2 remains unresolved as the frequency of deep intronic splicing variants has not been defined in high-risk familial breast/ovarian cancer families. This variant category is reported at significant frequency in other tumour predisposition genes, including NF1 and MSH2. We carried out comprehensive whole gene RNA analysis on 45 high-risk breast/ovary and male breast cancer families with no identified pathogenic variant on exonic sequencing and copy number analysis of BRCA1/2. In addition, we undertook variant screening of a 10-gene high/moderate risk breast/ovarian cancer panel by next generation sequencing. DNA testing identified the causative variant in 50/56 (89%) breast/ovarian/male breast cancer families with Manchester scores of >=50 with two variants being confirmed to affect splicing on RNA analysis. RNA sequencing of BRCA1/BRCA2 on 45 individuals from high-risk families identified no deep intronic variants and did not suggest loss of RNA expression as a cause of lost sensitivity. Panel testing in 42 samples identified a known RAD51D variant, a high-risk ATM variant in another breast ovary family and a truncating CHEK2 mutation. Current exonic sequencing and copy number analysis variant detection methods of BRCA1/2 have high sensitivity in high-risk breast/ovarian cancer families. Sequence analysis of RNA does not identify any variants undetected by current analysis of BRCA1/2. However, RNA analysis clarified the pathogenicity of variants of unknown significance detected by current methods. The low diagnostic uplift achieved through sequence analysis of the other known breast/ovarian cancer susceptibility genes indicates that further high-risk genes remain to be identified. PMID- 27273132 TI - Digital PCR for discriminating mosaic deletions and for determining proportion of tumor cells in specimen. AB - Mosaicism, presence of a genetic feature in only a subpopulation of cells, is frequent in de novo genetic diseases. Among large deletions covering the NF1 tumor suppressor gene, the frequency of mosaicism can be as high as 40% in de novo patients. In this study, we demonstrate the high potential of digital PCR in detecting large NF1 deletions and in discriminating mosaic cases. By simultaneously assessing the NF1 gene and a reference gene RPP30, deletions could be unambiguously distinguished from non-deletion samples. Performing the same assay for mixed samples from a DNA with a deletion and a non-deletion DNA, a highly significant linear relation was obtained between the set-up ratio of the two samples and the measured ratio of NF1/RPP30 (P<0.0001), suggesting the high potential of digital PCR in discriminating mosaic deletions. Furthermore, digital PCR detects NF1 allele loss in a tumor specimen that was not detected by loss of heterozygosity analysis using polymorphic markers due to high content of non tumor cells. Based on the measured ratio of NF1/RPP30, the proportion of the tumor cells in this specimen could be calculated as 25%. Our results demonstrate that dual-probe digital PCR is a simple and effective method for detecting deletions and for discriminating mosaic deletions. Furthermore, this method is sensitive for assigning somatic allele loss in tumor specimen and enables determining proportion of tumor cells. PMID- 27273133 TI - Joint Effect of Early Microvascular Damage in the Eye &Kidney on Risk of Cardiovascular Events. AB - Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD), but not all individuals require treatment. Retinal microvascular abnormalities and microalbuminuria reflect early systemic microvascular changes. We examined the joint effect of retinal abnormalities and microalbuminuria on CVD risk in an Asian cohort. We conducted a prospective, population-based study. Retinal abnormalities were defined as presence of retinopathy and/or retinal venular widening. Microalbuminuria was defined as urinary albumin: creatinine ratio between 30-300 mg/g. Incident CVD was defined as newly diagnosed clinical stroke, acute myocardial infarction or CVD death. Cox regression models were performed to determine the associations between retinal abnormalities and microalbuminuria with risk of CVD, while controlling for established risk factors. 3,496 participants (aged >= 40) were free of prevalent CVD. During the follow-up (5.8 years), 126 (3.60%) participants developed CVD. Persons presenting with both retinal abnormalities and microalbuminuria were 6.71 times (95% CI, 2.68, 16.79) as likely to have incident CVD compared with those without either abnormalities. There was a significant interaction effect between retinal abnormalities and microalbuminuria on incident CVD. Assessment of retinal abnormalities in patients with microalbuminuria may provide additional value in identifying persons at risk of developing CVD. PMID- 27273134 TI - Predictors of active cancer thromboembolic outcomes: validation of the Khorana score among patients with lung cancer. AB - Essentials Venous thromboembolism (VTE) prevention strategies require effective risk assessment models. We sought to validate the Khorana Risk Score (KRS) in patients with lung cancer. A high KRS was not predictive of VTE but was independently associated with all-cause mortality. Our findings stress the need for a lung cancer-specific VTE risk assessment model. SUMMARY: Objectives Lung cancer is strongly associated with venous thromboembolism (VTE), but primary prevention against VTE is not a validated management strategy. Risk assessment models will be necessary for efficient implementation of preventative strategies. Materials and methods Utilizing a prospectively collected lung cancer database, we aimed to validate the Khorana Risk Score (KRS) in the prediction of VTE among patients with lung cancer. VTE events were retrospectively identified by reviewers unaware of the clinical prediction score calculation. The association between KRS and the risk of VTE was examined using cumulative incidence function with competing risk models. Mortality prediction was evaluated as a secondary outcome. Results We included 719 patients in our review. The patients were predominantly older men with non-small cell lung cancer and 40% had metastatic disease at inception. The median follow-up was 15.2 months. There were 83 VTEs (11.5%) and 568 (78.8%) patients died. A high KRS (cumulative incidence, 12.4%; 95% confidence interval [CI], 6.4-20.5%) was not associated with VTE compared with an intermediate score (cumulative incidence, 12.1%; 95% confidence interval, 9.5-15.0%) in both univariate and multivariable analyses. However, a high KRS was a predictor of mortality (hazard ratio, 1.7; 95% CI, 1.4-2.2). Conclusions Among patients with lung cancer, the KRS did not stratify the patients at the highest risk of VTE. Improved risk stratification methods are needed for this group of patients prior to implementing a primary prevention strategy. PMID- 27273135 TI - The evaluation of meibomian gland function, morphology and related medical history in Asian adult blepharokeratoconjunctivitis patients. AB - PURPOSE: To evaluate the meibomian gland function, morphology and the related medical history of patients with blepharokeratoconjunctivitis (BKC) in comparison with healthy population and meibomian gland dysfunction (MGD)-induced evaporative dry eye (EDE) patients. METHODS: Twenty-two eyes of 22 Asian adult patients with BKC were enrolled as the BKC group. Healthy volunteers and MGD-induced EDE patients were recruited in a 1:1 ratio and were matched in age, and the gender compositions of the three groups were also comparable. Examinations included meibum quality, meibomian gland expressibility, meibomian gland dropout and relevant ocular surface tests. Related medical history was recorded. RESULTS: The BKC group had higher incidences of chalazion (OR 4.59, 95% CI 1.29-16.33) and eyelid surgery (OR 4.91, 95% CI 1.33-18.21) than the control group (chalazion, p = 0.007; eyelid surgery, p < 0.001) and EDE group (chalazion, p = 0.031; eyelid surgery, p = 0.005) had. All clinical indexes were worse in the BKC group than in the control group (all p < 0.05). The EDE group had better meibum quality (p = 0.049) and less meibomian gland dropouts (all p < 0.05) than the BKC group. The dropouts of the BKC group were the highest among the three groups, and the distribution over the tarsal plate was even in the BKC group (all p > 0.05). CONCLUSIONS: Patients with BKC had worse meibomian gland function, poorer morphology and a higher rate of medical histories related to the meibomian gland than the healthy population. The BKC clinical features of meibum quality and meibomian gland dropout were different from other MGD diseases. PMID- 27273136 TI - Hearing Health Care: Review of a Report From the National Academies of Sciences, Engineering, and Medicine. PMID- 27273137 TI - Analysis of extraembryonic mesodermal structure formation in the absence of morphological primitive streak. AB - During mouse gastrulation, the primitive streak is formed on the posterior side of the embryo. Cells migrate out of the primitive streak to form the future mesoderm and endoderm. Fate mapping studies revealed a group of cell migrate through the proximal end of the primitive streak and give rise to the extraembryonic mesoderm tissues such as the yolk sac blood islands and allantois. However, it is not clear whether the formation of a morphological primitive streak is required for the development of these extraembryonic mesodermal tissues. Loss of the Cripto gene in mice dramatically reduces, but does not completely abolish, Nodal activity leading to the absence of a morphological primitive streak. However, embryonic erythrocytes are still formed and assembled into the blood islands. In addition, Cripto mutant embryos form allantoic buds. However, Drap1 mutant embryos have excessive Nodal activity in the epiblast cells before gastrulation and form an expanded primitive streak, but no yolk sac blood islands or allantoic bud formation. Lefty2 embryos also have elevated levels of Nodal activity in the primitive streak during gastrulation, and undergo normal blood island and allantois formation. We therefore speculate that low level of Nodal activity disrupts the formation of morphological primitive streak on the posterior side, but still allows the formation of primitive streak cells on the proximal side, which give rise to the extraembryonic mesodermal tissues formation. Excessive Nodal activity in the epiblast at pre-gastrulation stage, but not in the primitive streak cells during gastrulation, disrupts extraembryonic mesoderm development. PMID- 27273138 TI - Dynamic single gold nanoparticle visualization by clinical intracoronary optical coherence tomography. AB - The potential use of Gold Nanoparticles (GNPs) as contrast agents for clinical intracoronary frequency domain Optical Coherence Tomography (OCT) is here explored. The OCT contrast enhancement caused by GNPs of different sizes and morphologies has been systematically investigated and correlated with their optical properties. Among the different GNPs commercially available with plasmon resonances close to the operating wavelength of intracoronary OCT (1.3 um), Gold Nanoshells (GNSs) have provided the best OCT contrast due to their largest scattering cross section at this wavelength. Clinical intracoronary OCT catheters are here demonstrated to be capable of three dimensional visualization and real time tracking of individual GNSs. Results here included open an avenue to novel application of intravascular clinical OCT in combination with GNPs, such as real time evaluation of intravascular obstructions or pressure gradients. PMID- 27273139 TI - The long-term development of public attitudes towards people with epilepsy in the Czech Republic: 1981, 1984, 1998 and 2009 studies. AB - OBJECTIVE: The long-term development of public attitudes towards people with epilepsy (PWE) was studied. METHODS: Four questions (Q) used in Czech questionnaires for studies in 1981, 1984, 1998 and 2009 concerned: Q1, familiarity with the concept of epilepsy; Q2, tolerance towards children with epilepsy; Q3, whether epilepsy is considered to be a mental disease; and Q4, attitudes towards employment of PWE. RESULTS: The quality of information about epilepsy increased significantly between 1981 and 1998, 1981 and 2009, and 1998 and 2009. The 1981 and 1984 studies reflected a level of information inferior to the levels seen in Germany and the USA, and the difference had almost disappeared in 1998 and 2009. CONCLUSIONS: The long-term follow-up studies in Czech Republic displayed a permanent increase in knowledge about epilepsy. This may reflect the progress in the spread of information, the efforts of patient associations and specialists and perhaps also a change in general attitudes towards people with disabilities. The dramatic change of information levels in Czech surveys could also reflect the change of the political system in 1989. A question that remains to be answered is the extent to which the positive trend reflects positive attitudes in real life. The answers to questions concerning whether people would be willing to help a person having a seizure remain unsatisfactory. Greater efforts should be made to improve the situation of PWE and to minimize their stigmatization. PMID- 27273140 TI - Cancer Screening Navigation: From Promising Practice to Standard of Care. PMID- 27273141 TI - Thromboelastography during coronary artery bypass grafting surgery of severe hemophilia A patient - the effect of heparin and protamine on factor VIII activity. AB - : Coronary artery bypass grafting surgery (CABG) in hemophilia patients is challenging. Thromboelastography (TEG) is useful to assess hemostasis perioperatively. A patient with severe hemophilia A underwent CABG with TEG studies. After factor VIII (FVIII) bolus dose, TEG was normalized. Following 'on pump' heparinization, protamine administration revealed prolonged TEG-R and TEG-R with heparinase confirming it, whereas the activated clotting time was normal, suggesting low FVIII activity rather than excess of heparin. Another FVIII bolus yielded complete normalization of all TEG parameters. Data are compatible with in vitro assays performed in our laboratory, showing that both heparin and protamine may impair measurable FVIII activity. The rational use of TEG measurements enabled more accurate hemostatic therapy application with regard to FVIII, heparin and protamine administration. Adopting this approach may lead to a better therapy tailoring for hemophilia patients undergoing CABG surgery. PMID- 27273142 TI - Simvastatin ameliorates deep vein thrombosis in rabbits by regulating the fibrinolytic system. AB - The study aimed to observe the therapeutic effect of simvastatin in a deep vein thrombosis (DVT) animal model and conduct a preliminary study into its mechanism. A total of 72 New Zealand white rabbits were randomly divided into control group (n = 18), low molecular weight heparin (LMWH) group (n = 18), simvastatin group (n = 18), and simvastatin + LMWH group (n = 18). A posterior vena cava thrombus model was established and interventions were administered according to the group procedures. Blood plasma was sampled before and 3, 7, and 14 days after the intervention when the vena cava (including thrombus) specimen was collected. Specimens were weighed, histopathologically examined, and monitored for changes in venous wall inflammation. Concentrations of P-selectin, plasminogen activator inhibitor (PAI-1), and the urokinase plasminogen activator (u-PA) activity were measured with enzyme-linked immunosorbent assay. P-selectin expression in the venous wall was measured with immunohistochemistry, and quantitative PCR detected the changes of local PAI-1/u-PA expression. Simvastatin and LMWH reduced the weight of the thrombus and promoted thrombus dissolution. Simvastatin significantly inhibited the systemic and local expression of P-selectin, whereas LMWH was inhibitory only at the late stage of the acute phase. Plasma active concentration and local gene expression of PAI-1 was inhibited by simvastatin, whereas for u-PA; it was promoted at the early stage of the acute phase, but inhibited in the late stage. Simvastatin inhibited the expression of inflammatory mediators, reduced the DVT inflammatory response, alleviated inflammatory injury and reduced thrombus formation. Simvastatin may provide a beneficial adjuvant therapy for DVT. PMID- 27273144 TI - Combined deficiency of factor V and factor VIII: management during cardiothoracic surgery. AB - : Combined factor V and factor VIII deficiency is an extremely rare bleeding disorder for which research is lacking. We present the case of a 33-year-old man requiring repeat mitral valve replacement. A multidisciplinary team approach was utilized to minimize his risk of bleeding which included the use of plasma exchange, intravenous factor replacement, and platelet transfusion. This approach created an operative experience that did not require blood transfusion or the use of other hemostatic medications. PMID- 27273143 TI - Surgical procedures in patients with Glanzmann's thrombasthenia: case series and literature review. AB - Glanzmann's thrombasthenia is a rare platelet function disorder with an autosomal recessive pattern of inheritance. Achieving haemostasis in such patients who undergo surgical procedures always poses a significant challenge. Herein we report six cases of Glanzmann's thrombasthenia, who underwent nine surgeries under the cover of platelet-rich concentrates with or without recombinant activated factor VII . Of these, five were major surgeries such as thyroidectomy, laparotomy, Hartmann's procedure, reversal of Hartmann's procedure and a complete dental extraction. All five procedures were successfully done without any major bleeding. The major cost incurred in these procedures is due to the large number of blood products used and recombinant activated factor VII if used. PMID- 27273145 TI - Implementation of a brief anxiety assessment and evaluation in a Department of Veterans Affairs geriatric primary care clinic. AB - Anxiety disorders are common and debilitating in older individuals, yet anxiety is often not formally assessed in primary care. We conducted a quality improvement project to examine the feasibility of implementing a brief anxiety assessment, the Geriatric Anxiety Inventory (GAI), in a Department of Veterans Affairs geriatric primary care clinic. We compared the GAI with a depression assessment, the 15-item Geriatric Depression Scale (GDS-15). Fifty older Veterans (mean = 78.5 +/- 7.4 yr) completed the GAI and GDS-15. Mean completion time and feedback to patients was brief (6.20 min; n = 10). Good internal consistency (alpha = 0.82) was found for GAI scores. Patients with psychiatric diagnoses obtained significantly higher GAI scores (mean = 4.73 +/- 1.15) compared with patients without psychiatric diagnoses (mean = 1.15 +/- 1.86, t(11.46) = -3.10, p = 0.01). Findings suggest that the GAI is acceptable to patients but may not be suitable for differentiating anxiety symptoms or disorders from depression. Interdisciplinary team members continued to implement the GAI after project completion to screen for and track anxiety symptoms in our geriatric primary care patients. Detecting anxiety with the GAI had the benefit of allowing providers to initiate conversations about available treatments and track symptoms as part of noting treatment progress. PMID- 27273146 TI - A systematic review of the use of quality-of-life instruments in randomized controlled trials for psoriasis. AB - Planners of interventional studies in psoriasis face the dilemma of selecting suitable quality-of-life (QoL) measures. Systematic reviews have the potential of identifying psychometrically sound measures in a given therapeutic area, while guiding the development of practice guidelines. The aim of this systematic review was to generate evidence of the use of QoL instruments in randomized controlled trials (RCTs) for interventions in psoriasis. The methodology followed the PRISMA guidelines. Six databases were searched with 388 search terms. Abstracts of articles were reviewed independently by two assessors, and a third adjudicator resolved any opinion differences. Risk of bias was assessed using the Jadad scale. Of 3646 screened publications, 99 articles (100 trials) met the eligibility criteria for inclusion, describing research on 33 215 patients. Thirty-three trials tested topical therapy, 18 systemic, 39 biologics, nine phototherapy and 10 other interventions. The Dermatology Life Quality Index (DLQI) was the most commonly used QoL instrument (83 studies, 83%), followed by the 36-Item Short Form Survey (SF-36) (31, 31%), EuroQoL-5D (EQ-5D) (15, 15%), Psoriasis Disability Index (14, 14%) and Skindex (five, 5%). There was widespread inconsistency in the way that QoL data were reported. Of the 100 trials identified, 37 reported minimal clinically important difference (MCID): 32 for DLQI, 10 for SF-36 and six for EQ-5D. QoL measurement is increasingly being reported in RCTs of psoriasis. Formal guidelines are needed for assessment and publishing of QoL data. Researchers should consider whether MCID information is available, and development of MCID data should be encouraged. PMID- 27273147 TI - Geographically Related Variation in Epicuticular Wax Traits of Pinus nigra Populations from Southern Carpathians and Central Balkans - Taxonomic Considerations. AB - The chemical composition of epicuticular waxes of nine populations from three Pinus nigra J. F. Arnold subspecies (namely subsp. nigra, subsp. banatica (Borbas) Novak, and subsp. pallasiana (Lamb.) Holmboe) from Southern Carpathians and central Balkan Peninsula were analyzed using GC/MS and GC/FID chromatography, and multivariate statistical techniques with respect to biogeography and taxonomy. In the needle waxes, four primary alcohols and 14 n-alkanes ranging from C21 to C33 were identified, and the most abundant compounds were the four odd-numbered n-alkanes C27 , C25 , C23 , and C29. Multivariate statistical analyses (CDA and CA) have shown existence of three P. nigra groups and suggested clinal differentiation as a mechanism of genetic variation across a geographic area: the first group consisted of the southernmost populations of subsp. pallasiana from Macedonia, the second consisted of the northernmost subsp. banatica populations from Romania, while all populations in Serbia described as three different subspecies (nigra, banatica, and pallasiana) formed the third group together with subsp. nigra population from Bosnia and Herzegovina. According to simple linear regression, geographic latitude and four bioclimatic parameters were moderately correlated with the contents of epicuticular wax compounds that are important in population discrimination, while stepwise multiple regression showed that latitude participated in most of the regression models for predicting the composition of the epicuticular waxes. These results agree with CDA and CA analysis, and confirmed the possibility of recognition of fine geographic differentiation of the analyzed P. nigra populations. PMID- 27273148 TI - Preclinical study of transcervical upper mediastinal dissection for esophageal malignancy by robot-assisted surgery. AB - BACKGROUND: Robotic surgical systems are potentially applicable to transcervical mediastinal lymph dissection for esophageal malignancy. METHODS: Robot-assisted surgery was performed on a male fresh-frozen human cadaver. Devices for single port laparoscopic surgery were deployed via one small incision in the left clavicular area. The task for the robot-assisted surgery was the upper mediastinal dissection to the level of the left main bronchus and en bloc harvest of the lymph nodes adherent to the left recurrent laryngeal nerve. RESULTS: An up angled 30 degrees scope in the 6 o'clock port and two robotic arms from the 3 and 9 o'clock ports worked effectively together. No collisions of the devices inside the cadaveric body or unexpected traumatic events occurred. CONCLUSION: The robotic surgical system can be used safely for the upper mediastinal dissection. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273150 TI - Barriers and facilitators for implementing a new screening tool in an emergency department: A qualitative study applying the Theoretical Domains Framework. AB - AIM: The aim was to identify the factors that were perceived as most important as facilitators or barriers to the introduction and intended use of a new tool in the emergency department among nurses and a geriatric team. BACKGROUND: A high incidence of functional decline after hospitalisation for acute medical illness has been shown in the oldest patients and those who are physically frail. In Denmark, more than 35% of older medical patients acutely admitted to the emergency department are readmitted within 90 days after discharge. A new screening tool for use in the emergency department aiming to identify patients at particularly high risk of functional decline and readmission was developed. DESIGN: Qualitative study based on semistructured interviews with nurses and a geriatric team in the emergency department and semistructured single interviews with their managers. METHODS: The Theoretical Domains Framework guided data collection and analysis. Content analysis was performed whereby new themes and themes already existing within each domain were described. RESULTS: Six predominant domains were identified: (1) professional role and identity; (2) beliefs about consequences; (3) goals; (4) knowledge; (5) optimism and (6) environmental context and resources. The content analysis identified three themes, each containing two subthemes. The themes were professional role and identity, beliefs about consequences and preconditions for a successful implementation. CONCLUSIONS: Two different cultures were identified in the emergency department. These cultures applied to different professional roles and identity, different actions and sense making and identified how barriers and facilitators linked to the new screening tool were perceived. RELEVANCE FOR CLINICAL PRACTICE: The results show that different cultures exist in the same local context and influence the perception of barriers and facilitators differently. These cultures must be identified and addressed when implementation is planned. PMID- 27273149 TI - Pharmacokinetic Effects of Isavuconazole Coadministration With the Cytochrome P450 Enzyme Substrates Bupropion, Repaglinide, Caffeine, Dextromethorphan, and Methadone in Healthy Subjects. AB - This report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23). Compared with each drug alone, coadministration with isavuconazole changed the area under the concentration-time curves (AUCinfinity ) and maximum concentrations (Cmax ) as follows: bupropion, AUCinfinity reduced 42%, Cmax reduced 31%; repaglinide, AUCinfinity reduced 8%, Cmax reduced 14%; caffeine, AUCinfinity increased 4%, Cmax reduced 1%; dextromethorphan, AUCinfinity increased 18%, Cmax increased 17%; R-methadone, AUCinfinity reduced 10%, Cmax increased 3%; S-methadone, AUCinfinity reduced 35%, Cmax increased 1%. In all studies, there were no deaths, 1 serious adverse event (dextromethorphan study; perioral numbness, numbness of right arm and leg), and adverse events leading to study discontinuation were rare. Thus, isavuconazole is a mild inducer of CYP2B6 but does not appear to affect CYP1A2-, CYP2C8-, or CYP2D6-mediated metabolism. PMID- 27273151 TI - Sesterterpene ophiobolin biosynthesis involving multiple gene clusters in Aspergillus ustus. AB - Terpenoids are the most diverse and abundant natural products among which sesterterpenes account for less than 2%, with very few reports on their biosynthesis. Ophiobolins are tricyclic 5-8-5 ring sesterterpenes with potential pharmaceutical application. Aspergillus ustus 094102 from mangrove rizhosphere produces ophiobolin and other terpenes. We obtained five gene cluster knockout mutants, with altered ophiobolin yield using genome sequencing and in silico analysis, combined with in vivo genetic manipulation. Involvement of the five gene clusters in ophiobolin synthesis was confirmed by investigation of the five key terpene synthesis relevant enzymes in each gene cluster, either by gene deletion and complementation or in vitro verification of protein function. The results demonstrate that ophiobolin skeleton biosynthesis involves five gene clusters, which are responsible for C15, C20, C25, and C30 terpenoid biosynthesis. PMID- 27273153 TI - First Atroposelective Total Synthesis of Enantiomerically Pure Ancistrocladidine and Ancistrotectorine. AB - The first regio- and stereoselective total synthesis of the axially chiral 7,3' coupled naphthylisoquinoline alkaloids ancistrocladidine (1) and ancistrotectorine (2) has been described. Both possess a 7,3'-coupled axis, which before now, was difficult to attain synthetically. Moreover, target 2 has a sensitive relative cis-array of the two methyl groups at C1 and C3 in the tetrahydroisoquinoline part. The key step in the chosen strategy was the construction of the biaryl axis in accordance with the "lactone method": the two molecular halves, which were activated in an "inverse-halogenated" form, were prefixed by an ester bridge, followed by intramolecular coupling, and atroposelective cleavage of the lactone auxiliary bridge delivered the desired biaryl scaffold. PMID- 27273152 TI - Genome sequence of Perigonia lusca single nucleopolyhedrovirus: insights into the evolution of a nucleotide metabolism enzyme in the family Baculoviridae. AB - The genome of a novel group II alphabaculovirus, Perigonia lusca single nucleopolyhedrovirus (PeluSNPV), was sequenced and shown to contain 132,831 bp with 145 putative ORFs (open reading frames) of at least 50 amino acids. An interesting feature of this novel genome was the presence of a putative nucleotide metabolism enzyme-encoding gene (pelu112). The pelu112 gene was predicted to encode a fusion of thymidylate kinase (tmk) and dUTP diphosphatase (dut). Phylogenetic analysis indicated that baculoviruses have independently acquired tmk and dut several times during their evolution. Two homologs of the tmk-dut fusion gene were separately introduced into the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) genome, which lacks tmk and dut. The recombinant baculoviruses produced viral DNA, virus progeny, and some viral proteins earlier during in vitro infection and the yields of viral occlusion bodies were increased 2.5-fold when compared to the parental virus. Interestingly, both enzymes appear to retain their active sites, based on separate modeling using previously solved crystal structures. We suggest that the retention of these tmk-dut fusion genes by certain baculoviruses could be related to accelerating virus replication and to protecting the virus genome from deleterious mutation. PMID- 27273156 TI - Phosphoproteome analysis of the MAPK pathway reveals previously undetected feedback mechanisms. AB - The RAS-RAF-MEK-ERK (MAPK) pathway is prevalently perturbed in cancer. Recent large-scale sequencing initiatives profiled thousands of tumors providing insight into alterations at the DNA and RNA levels. These efforts confirmed that key nodes of the MAPK pathway, in particular KRAS and BRAF, are among the most frequently altered proteins in cancer. The establishment of targeted therapies, however, has proven difficult. To decipher the underlying challenges, it is essential to decrypt the phosphorylation network spanned by the MAPK core axis. Using mass spectrometry we identified 2241 phosphorylation sites on 1020 proteins, and measured their responses to inhibition of MEK or ERK. Multiple phosphorylation patterns revealed previously undetected feedback, as upstream signaling nodes, including receptor kinases, showed changes at the phosphorylation level. We provide a dataset rich in potential therapeutic targets downstream of the MAPK cascade. By integrating TCGA (The Cancer Genome Atlas) data, we highlight some downstream phosphoproteins that are frequently altered in cancer. All MS data have been deposited in the ProteomeXchange with identifier PXD003908 (http://proteomecentral.proteomexchange.org/dataset/PXD003908). PMID- 27273157 TI - Switching of chiral magnetic skyrmions by picosecond magnetic field pulses via transient topological states. AB - Magnetic chiral skyrmions are vortex like spin structures that appear as stable or meta-stable states in magnetic materials due to the interplay between the symmetric and antisymmetric exchange interactions, applied magnetic field and/or uniaxial anisotropy. Their small size and internal stability make them prospective objects for data storage but for this, the controlled switching between skyrmion states of opposite polarity and topological charge is essential. Here we present a study of magnetic skyrmion switching by an applied magnetic field pulse based on a discrete model of classical spins and atomistic spin dynamics. We found a finite range of coupling parameters corresponding to the coexistence of two degenerate isolated skyrmions characterized by mutually inverted spin structures with opposite polarity and topological charge. We demonstrate how for a wide range of material parameters a short inclined magnetic field pulse can initiate the reliable switching between these states at GHz rates. Detailed analysis of the switching mechanism revealed the complex path of the system accompanied with the excitation of a chiral-achiral meron pair and the formation of an achiral skyrmion. PMID- 27273159 TI - An all-in-one tympanostomy tube insertion device: results of usability testing in fourteen cadaveric and twelve plastic model ears. PMID- 27273158 TI - Viral Decay Dynamics and Mathematical Modeling of Treatment Response: Evidence of Lower in vivo Fitness of HIV-1 Subtype C. AB - BACKGROUND: Despite the high prevalence of HIV-1 subtype C (HIV-1C) worldwide, information on HIV-1C viral dynamics and response to antiretroviral therapy (ART) is limited. We sought to measure viral load decay dynamics during treatment and estimate the within-host basic reproductive ratio, R0, and the critical efficacy, epsilonc, for successful treatment of HIV-1C infection. METHODS: Individuals initiated on first-line ART in India and monitored for 6 months of treatment were considered. Viral load, CD4 count, and adherence data were collected at baseline, 4, 12, 16 and 24 weeks after ART initiation. Drug resistance genotyping was performed at baseline. R0 and epsilonc were estimated using a mathematical model. RESULTS: Among 257 patients with complete data, mean baseline viral load was 5.7 log10 copies per milliliter and median CD4 count was 165 cells per cubic millimeter. Primary drug resistance was present in 3.1% at baseline. At 6 months, 87.5% had undetectable viral load, indicating excellent response to ART despite high baseline viremia. After excluding those with transmitted resistance, suboptimal adherence and viral rebound, data from 112 patients were analyzed using a mathematical model. We estimated the median R0 to be 5.3. The corresponding epsilonc was ~0.8. CONCLUSIONS: These estimates of R0 and epsilonc are smaller than current estimates for HIV-1B, suggesting that HIV-1C exhibits lower in vivo fitness compared with HIV-1B, which allows successful treatment despite high baseline viral loads. The lower fitness, and potentially lower virulence, together with high viral loads may underlie the heightened transmission potential of HIV-1C and its growing global spread. PMID- 27273160 TI - Transcriptional enhancement of Smn levels in motoneurons is crucial for proper axon morphology in zebrafish. AB - An unresolved mystery in the field of spinal muscular atrophy (SMA) is why a reduction of the ubiquitously expressed Smn protein causes defects mostly in motoneurons. We addressed the possibility that this restricted vulnerability stems from elevated Smn expression in motoneurons. To explore this, we established an ex vivo zebrafish culture system of GFP-marked motoneurons to quantitatively measure Smn protein and smn mRNA levels as well as promoter activity in motoneurons versus other cell types. Importantly, we uncovered that Smn levels are elevated in motoneurons by means of transcriptional activation. In addition, we identified the ETS family transcription factor Etv5b to be responsible for increased smn transcription in motoneurons. Moreover, we established that the additional supply of Smn protein in motoneurons is necessary for proper axonogenesis in a cell-autonomous manner. These findings demonstrate the reliance of motoneurons on more Smn, thereby adding a novel piece of evidence for their increased vulnerability under SMA conditions. PMID- 27273161 TI - Reliability of the German version of the Children's Assessment of Participation and Enjoyment (CAPE) and Preferences for Activities of Children (PAC). AB - BACKGROUND: The introduction of the International Classification of Functioning, Disabilities and Health of the World Health Organization in 2001 made social participation a major rehabilitation outcome and the ultimate goal of rehabilitation services. There is no available instrument to measure the youth participation in leisure activities apart from asking the youth themselves. The goal of this study was to present a German version of the Children's Assessment of Participation and Enjoyment and Preferences for Activities of Children (CAPE/PAC). METHODS: The CAPE/PAC questionnaire was translated into German, a cultural adaptation process was designed and a reliability study was conducted. One hundred and fifty-two youths with and without disabilities, with a mean age of 15.2 years (standard deviation 1.7), participated in the study. The participants completed CAPE and PAC twice within 4 weeks. Reliability was examined by intraclass correlation coefficients, standard error of measurement, smallest detectable change and Cronbach's alpha. RESULTS: The absolute values of participation differ between the typically developed youth group and those with impairments; the reliability of the CAPE/PAC is comparable in both groups. Intraclass correlation coefficients ranged from 0.43 to 0.74 for the CAPE and from 0.71 to 0.83 for the PAC in all participants. The alpha values for internal consistency ranged from 0.42 to 0.82 for the CAPE and from 0.65 to 0.92 for the PAC. CONCLUSIONS: The German version of the PAC showed satisfactory reliability; however, reliability was not satisfactory for all scores of the CAPE, but comparable with versions in other languages. The need for newly developed participation measurements requires further discussion. PMID- 27273162 TI - Gene frequency and haplotype distribution of hemoglobin E among seven minority groups of Yunnan, China. AB - OBJECTIVE: The aim of this study was to determine the distribution and origin of hemoglobin E (HbE) in seven minority groups from various geographical regions of the malaria-endemic Yunnan province, southwestern China, which have similar ethnic origins and geographic relationships with HbE-prevalent populations of Southeast Asian countries. METHODS: By using Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) methods, the prevalence of HbE was examined in 1488 individuals from seven native minority groups of Yunnan, and beta-globin gene cluster haplotypes were determined on 1420 chromosomes. RESULTS: The prevalence of HbE in the study populations ranged from 1.5 to 39.1%. Higher HbE prevalence was correlated with the minority groups of Tibeto-Burman origin and groups from the Dehong district. The betaE -globin genes in Yunnan were mostly associated with three haplotypes [-+++++-], [+----+-], and [-+-+++-] on chromosomes with gene framework 2. Interestingly, the predominant betaE associated haplotype in Yunnan minorities was remarkably different from that in other previously reported populations. This study, for the first time, reports population-based data on the heterogeneity of HbE gene frequencies and haplotype distribution in native minorities from southwestern China. CONCLUSIONS: Natural selection based on the presence of malaria, ethnic origin, and epistatic interactions may be factors of varying importance for the remarkable variation in HbE frequency among these minority groups. In addition, there appears to be a common origin of the betaE -globin gene in populations from Yunnan and Southeast Asia. Am. J. Hum. Biol. 28:927-931, 2016. (c) 2016Wiley Periodicals, Inc. PMID- 27273163 TI - Realization of Plasmonic Microcavity with Full Transverse and Longitudinal Mode Selection. AB - Surface plasmon polaritons (SPPs) manipulation is of vital importance to construct ultracompact integrated micro/nano-optical devices and systems. Here we report the design, fabrication, and characterization of a SPP microcavity with full transverse and longitudinal mode selection and control on the surface of gold film. The designed microcavity supports the fundamental and first-order transverse modes of Gaussian mode beam with controllable longitudinal modes, respectively. The transverse mode is determined by two holographic mirrors made from deliberately designed groove patterns via the surface electromagnetic wave holography methodology, while the longitudinal mode is determined by the length of cavity. Both numerical simulations and leaky-wave SPP mode observations confirm the realization of full mode selection in the fabricated cavity. Our work opens up a powerful way to fully explore longitudinal and transverse mode control in SPP microcavities, which will be beneficial for light-matter interaction enhancement, construction of novel SPP nanolaser and microlaser, optical sensing, and optical information processing. PMID- 27273164 TI - PAS or plasma for storage of platelets? A concise review. AB - Platelet additive solutions (PASs) are becoming increasingly popular for storage of platelets, and PAS is steadily replacing plasma as the storage medium of platelets. PASs are electrolyte solutions intended for storage of platelets, and they are used to modulate the quality of the platelets by adding specific ingredients. All currently available PASs contain acetate. Acetate reduces the amount of glucose that is oxidised into lactic acid and thereby prevents the lowering of pH, which decreases platelet quality. Furthermore, the oxidation of acetate leads to the production of bicarbonate, which serves as buffer. The presence of potassium and magnesium in PAS prevents the lowering of pH and reduces the degree of spontaneous activation of the platelets during storage. In the hospital, platelets stored in PAS result in about half of the number of allergic transfusion reactions as compared with platelets in plasma. Recovery and survival after transfusion, as well as corrected count increments, are at least as good for platelets in PAS as for plasma, and recent data suggest they may even be better. Therefore, with the current generation of PASs, PAS should be preferred over the use of plasma for the storage of platelet concentrates. PMID- 27273165 TI - Rare single-molecule magnets with six-coordinate Ln(III) ions exhibiting a trigonal antiprism configuration. AB - Four Ni-Ln-Ni heterometallic complexes, [Ni2LnL2]NO3.3H2O (H3L = tri(((3 methoxysalicylidene)amino)ethyl)amine, Ln = Gd for , Tb for and Dy for , respectively) and [Ni2DyL2]ClO4.MTBE.0.65H2O (, MTBE = methyl tert-butyl ether) have been synthesized by diffusion of methyl tert-butyl ether vapor into the reaction solution. The X-ray analyses demonstrated that the Gd(III) ion in exhibits rare seven-coordination, the Tb(III) and Dy(III) ions in display unusual six-coordination, and two Ni(II) ions and one Ln(III) ion are bridged by six phenolato atoms to form linear Ni-Ln-Ni heterotrinuclear complexes for . All complexes exhibit weak ferromagnetic interactions between Ni(II) and Ln(III) ions. Alternating current susceptibility measurements demonstrated that compounds and behave as single-molecule magnets with the effective energy barriers of 14.17 and 11.13 K under zero direct current field. They are rare single-molecule magnets containing six-coordinate Dy(III) ions. PMID- 27273166 TI - Label-free offline versus online activity methods for nucleoside diphosphate kinase b using high performance liquid chromatography. AB - Nucleoside diphosphate kinase from Leishmania spp. (LmNDKb) has recently been described as a potential drug target to treat leishmaniasis disease. Therefore, screening of LmNDKb ligands requires methodologies that mimic the conditions under which LmNDKb acts in biological systems. Here, we compare two label-free methodologies that could help screen LmNDKb ligands and measure NDKb activity: an offline LC-UV assay for soluble LmNDKb and an online two-dimensional LC-UV system based on LmNDKb immobilised on a silica capillary. The target enzyme was immobilised on the silica capillary via Schiff base formation (to give LmNDKb ICER-Schiff) or affinity attachment (to give LmNDKb-ICER-His). Several aspects of the ICERs resulting from these procedures were compared, namely kinetic parameters, stability, and procedure steps. Both the LmNDKb immobilisation routes minimised the conformational changes and preserved the substrate binding sites. However, considering the number of steps involved in the immobilisation procedure, the cost of reagents, and the stability of the immobilised enzyme, immobilisation via Schiff base formation proved to be the optimal procedure. PMID- 27273169 TI - A Review of the Research in Emotionally Focused Therapy for Couples. AB - Emotionally Focused Therapy for Couples (EFT) is a brief evidence-based couple therapy based in attachment theory. Since the development of EFT, efficacy and effectiveness research has accumulated to address a range of couple concerns. EFT meets or exceeds the guidelines for classification as an evidence-based couple therapy outlined for couple and family research. Furthermore, EFT researchers have examined the process of change and predictors of outcome in EFT. Future research in EFT will continue to examine the process of change in EFT and test the efficacy and effectiveness of EFT in new applications and for couples of diverse backgrounds and concerns. PMID- 27273167 TI - Critical comparison of elastography methods to assess chronic liver disease. AB - Staging of liver fibrosis and diagnosis, or exclusion, of early compensated liver cirrhosis are important in the treatment decisions and surveillance of patients with chronic liver disease. Good diagnostic accuracy, increased availability and the possibility to perform follow-up examinations led to the implementation of noninvasive methods into clinical practice. Noninvasive tests are increasingly included in national and international guidelines, leaving liver biopsy reserved for patients with unexplained discordance or suspected additional aetiologies of liver disease. In addition to staging of liver fibrosis, data on the prognostic value of these methods have increased in the past few years and are of great importance for patient care. This Review focuses on elastography methods for noninvasive assessment of liver fibrosis, disease severity and prognosis. Although liver elastography started with transient elastography, at present all large ultrasonography companies offer an elastography technique integrated in their machines. The goal of this Review is to summarize the methodological problems of noninvasive tests in general, in addition to providing an overview on currently available techniques and latest developments in liver elastography. PMID- 27273170 TI - Resonantly Enhanced Betatron Hard X-rays from Ionization Injected Electrons in a Laser Plasma Accelerator. AB - Ultrafast betatron x-ray emission from electron oscillations in laser wakefield acceleration (LWFA) has been widely investigated as a promising source. Betatron x-rays are usually produced via self-injected electron beams, which are not controllable and are not optimized for x-ray yields. Here, we present a new method for bright hard x-ray emission via ionization injection from the K-shell electrons of nitrogen into the accelerating bucket. A total photon yield of 8 * 10(8)/shot and 10(8 )photons with energy greater than 110 keV is obtained. The yield is 10 times higher than that achieved with self-injection mode in helium under similar laser parameters. The simulation suggests that ionization-injected electrons are quickly accelerated to the driving laser region and are subsequently driven into betatron resonance. The present scheme enables the single-stage betatron radiation from LWFA to be extended to bright gamma-ray radiation, which is beyond the capability of 3(rd) generation synchrotrons. PMID- 27273172 TI - Seek first to understand. PMID- 27273168 TI - The role of the gut microbiota in NAFLD. AB - NAFLD is now the most common cause of liver disease in Western countries. This Review explores the links between NAFLD, the metabolic syndrome, dysbiosis, poor diet and gut health. Animal studies in which the gut microbiota are manipulated, and observational studies in patients with NAFLD, have provided considerable evidence that dysbiosis contributes to the pathogenesis of NAFLD. Dysbiosis increases gut permeability to bacterial products and increases hepatic exposure to injurious substances that increase hepatic inflammation and fibrosis. Dysbiosis, combined with poor diet, also changes luminal metabolism of food substrates, such as increased production of certain short-chain fatty acids and alcohol, and depletion of choline. Changes to the microbiome can also cause dysmotility, gut inflammation and other immunological changes in the gut that might contribute to liver injury. Evidence also suggests that certain food components and lifestyle factors, which are known to influence the severity of NAFLD, do so at least in part by changing the gut microbiota. Improved methods of analysis of the gut microbiome, and greater understanding of interactions between dysbiosis, diet, environmental factors and their effects on the gut-liver axis should improve the treatment of this common liver disease and its associated disorders. PMID- 27273171 TI - Mutational Analysis of Prostate-Specific Antigen Defines the Intrinsic Proteolytic Activity of the proPSA Zymogen. AB - BACKGROUND: Prostate-specific antigen (PSA) is an important prostate cancer biomarker. It is also a protease expressed at high concentrations by the normal and malignant prostate. PSA is secreted as a zymogen (proPSA) with an inhibitory prodomain that must be removed for full activity. ProPSA variants, assumed to be inactive, are found in the blood of prostate cancer patients, and are indicative of poor clinical outcome. Despite the abundance of clinical reports, our understanding of PSA's enzymology is limited, in part due to a lack of appropriate experimental systems. We sought to develop a series of PSA-derived mutants that would help to enhance our understanding of the gene. METHODS: Sixteen rPSA variants were generated and characterized by a variety of biochemical methods. RESULTS: The wildtype cDNA (WT) provided the template for generating a panel of recombinants. These included variants that abolished removal of the prodomain (R24A), disabled its enzymatic activity (S213A), and/or facilitated a cell-based conversion to the active conformation (FR). The purified variants' proteolytic activity was examined using a fluorogenic substrate, known PSA-cleavable proteins, and physiologically relevant inhibitors. Upon demonstrating our successful generation and purification of the PSA variants, we characterized proPSA activity, describing cleavage of synthetic and biologic substrates, but not serum protease inhibitors. This finding was exploited in the development of a self-activating mutant (PSA_QY) that exhibited the greatest enzymatic activity of all the variants. CONCLUSIONS: The system described herein will prove useful for varied applications. ProPSA is partially functional with relatively high activity compared to the mature enzyme. In demonstrating the zymogen's intrinsic activity, we suggest that the proPSA in prostate cancer patient serum is not inert. This may have implications for our understanding of the disease. Prostate 76:1203-1217, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273173 TI - New drugs 2016, part 2. PMID- 27273174 TI - Empathic responsiveness and helping behaviours in young children with Williams syndrome. AB - BACKGROUND: Anecdotal and caregiver reports often highlight the sociability and empathy of children with Williams syndrome (WS), a genetically based neurodevelopmental disorder characterised by a distinctive, cognitive and social phenotype. Despite these characteristics, people with WS have many difficulties navigating the social world. In this study, we investigated whether the heightened social motivation and empathy demonstrated by children with WS lead to prosocial behaviours such as instrumental helping. METHODS: We compared 2;8 to 5;8 year olds with WS to an age-matched and developmental quotient-matched group of children with Down syndrome (DS) and an age-matched group of typically developing children, in their responses to semi-structured naturalistic situations designed to elicit empathic and helping behaviours. RESULTS: Children with WS showed more empathic concern than both comparison groups towards a person in distress but did not differ from controls in their level of helping behaviour. Children in both the WS and DS groups consistently received higher ratings on empathy than on helpfulness, in contrast to the balanced profile shown by the typically developing children. DISCUSSION: Findings suggest that the heightened emotional responsivity displayed by children with WS or DS does not readily translate into other forms of socially competent behaviour. The complex relations between empathy and prosocial behaviours in typical and atypical development are discussed. PMID- 27273175 TI - Formation of the syn isomer of [Fe(IV)(Oanti)(TMC)(NCMe)](2+) in the reaction of Lewis acids with the side-on bound peroxo ligand in [Fe(III)(eta(2)-O2)(TMC)](.). AB - We demonstrate that the reactions of [Fe(III)(eta(2)-O2)(TMC)](+) (TMC = tetramethylcyclam) with Lewis acids (H(+) and NO(+)) afford the recently described syn isomer of [Fe(IV)(O)(TMC)(NCMe)](2+) (and not the anti isomer as had been tacitly assumed). This outcome is a logical consequence of the fact that the side-on peroxo ligand is bound to the syn face of the Fe(TMC) unit in the precursor. PMID- 27273176 TI - High-Resolution Sonography as an Additional Diagnostic and Prognostic Tool to Monitor Disease Activity in Leprosy: A Two-Year Prospective Study. AB - PURPOSE: Early diagnosis and treatment of leprosy and leprosy reactions are essential to prevent stigmatizing deformities and disability. Although the incidence of leprosy has decreased enormously, grade 2 disability due to nerve injury has remained the same. New tools are needed to better diagnose and monitor leprosy reactions and associated neuritis and this study assessed whether high resolution sonography (HRUS) can be used as such a tool. MATERIALS AND METHODS: During a prospective follow-up period of 2 years at regular intervals, we performed clinical examination to assess sensory and motor function and HRUS of the four main peripheral nerves in 57 patients, of whom 36 were with reactions and 21 were without reactions. Normative data of the cross-sectional area (CSA) of these nerves were obtained from 55 healthy subjects (HS). Color Doppler (CD) was used to study blood flow in the nerves. RESULTS: At the baseline visit and during follow-up, all four nerves were significantly thicker in patients with leprosy reactions in comparison to HS (p < 0.0001) and to a lesser extent also in comparison to patients without reactions ranging from a p-value of < 0.05 to < 0.0001 in the different nerves tested. During follow-up, the nerve size did not change significantly in patients without reactions, while it decreased significantly in patients with reactions. At baseline, endoneural blood flow was present only in patients with reactions. This occurred in 20 of the 36 (55 %) patients (49 nerves) and decreased to only 1 patient (2.7 %) at the end of the follow-up period. CONCLUSION: This prospective study demonstrates the ability of HRUS to monitor disease activity and the effect of treatment in patients with leprosy reactions by determining changes in nerve size and vascularity, which are indicators of peripheral nerve involvement and damage. PMID- 27273177 TI - Reliability Criteria for Liver Stiffness Measurements with Real-Time 2D Shear Wave Elastography in Different Clinical Scenarios of Chronic Liver Disease. AB - PURPOSE: Liver stiffness measurement by real-time 2-dimensional shear wave elastography (2D-SWE) lacks universal reliability criteria. We sought to assess whether previously published 2D-SWE reliability criteria for portal hypertension were applicable for the evaluation of liver fibrosis and cirrhosis, and to look for criteria that minimize the risk of misclassification in this setting. MATERIALS AND METHODS: In a biopsy-controlled diagnostic study, we obtained five 2D-SWE measurements of optimal image quality. Correctly classified cases of fibrosis and cirrhosis were compared to misclassified cases. We compared reliability predictors (standard deviation (SD), SD/mean, size of region of interest (ROI) and difference between a single measurement and the patient's median) with those obtained in a prior study on clinically significant portal hypertension. RESULTS: We obtained 678 2D-SWE measurements from 142 patients. Overall, the variability in liver stiffness within single 2D-SWE measurements was low (SD = 1.1 +/- 1.5kPa; SD/mean = 12 +/- 9 %). Intra-observer analysis showed almost perfect concordance (intraclass correlation coefficient = 0.95; 95 % CI 0.94 - 0.96; average difference from median = 0.4 +/- 0.9kPa). For the diagnosis of cirrhosis, a smaller SD (optimally <= 1.75 kPa) and larger ROI size (optimally >= 18 mm) were associated with higher accuracy. Similarly, within the published cohort of patients assessed for portal hypertension, a low variability of measurements was associated with high reliability. CONCLUSION: A high quality 2D SWE elastogram ensures low variability and high reliability, regardless of indication. We recommend aiming for a combination of low standard deviation and large ROI. PMID- 27273179 TI - Fatal warm autoimmune hemolytic anemia in a child due to IgM-type autoantibodies. AB - Herein is described a case of immunoglobulin M (IgM) warm autoimmune hemolytic anemia (AIHA) in a child who consequently died within 3 days of clinical onset. A previously healthy 11-year-old boy presented with fever, anemia, jaundice, and deteriorating consciousness. On direct agglutination test against group O red blood cells, agglutination was seen even at 37 degrees C in saline, which was abolished on dithiothreitol treatment of the serum, indicating that the responsible autoantibody was IgM and had a warm-reactive capacity. A diagnosis of IgM warm AIHA was therefore made. Hemagglutination in the visceral capillaries was considered as the direct cause of organ dysfunction. The patient died due to respiratory failure. IgM warm AIHA is a very severe condition that is difficult to reverse in an advanced state. Both prompt, definite diagnosis and intervention are therefore vital to prevent severe multi-organ dysfunction in cases of IgM warm AIHA. PMID- 27273178 TI - Structural Ultrasound of the Medial Temporal Lobe in Alzheimer's Disease. AB - Purpose One of the anatomical hallmarks of Alzheimer's disease (AD) is the atrophy of the medial temporal lobe (MTL), yet cost-effective and broadly available methodological alternatives to the current imaging tools for screening of this brain area are not currently available. Materials and Methods Using structural transcranial ultrasound (TCS), we attempted to visualize and measure the MTL, and compared the results of 32 AD patients and 84 healthy controls (HC). The MTL and the surrounding space were defined in the coronal plane on TCS. A ratio of the height of the MTL/height of the choroidal fissure (M/F) was calculated in order to obtain a regional proportion. Results An insufficient temporal bone window was identified in 22 % of the AD patients and 12 % of the HCs. The results showed that the ratio of M/F was significantly smaller in the AD group on both sides (p = 0.004 right, p = 0.007 left side). Furthermore, the M/F ratio made it possible to discriminate AD patients from HCs with a sensitivity of 83 % (right)/73 % (left) and a specificity of 76 % (right)/72 % (left) which is basically comparable to results published for magnetic resonance imaging. The measurements showed substantial intra/interrater reliability (ICC:0.79/0.69). Conclusion These results suggest that utilization of structural TCS may possibly constitute a cheap and easy-to-use supplement to other techniques for the diagnosis of AD. It may be especially useful as a screening tool in the large population of individuals with cognitive decline. Further studies are needed to validate this novel method. PMID- 27273193 TI - Understanding M-ligand bonding and mer-/fac-isomerism in tris(8 hydroxyquinolinate) metallic complexes. AB - Tris(8-hydroxyquinolinate) metallic complexes, Mq3, are one of the most important classes of organic semiconductor materials. Herein, the nature of the chemical bond in Mq3 complexes and its implications on their molecular properties were investigated by a combined experimental and computational approach. Various Mq3 complexes, resulting from the alteration of the metal and substitution of the 8 hydroxyquinoline ligand in different positions, were prepared. The mer-/fac isomerism in Mq3 was explored by FTIR and NMR spectroscopy, evidencing that, irrespective of the substituent, mer- and fac-are the most stable molecular configurations of Al(iii) and In(iii) complexes, respectively. The relative M ligand bond dissociation energies were evaluated experimentally by electrospray ionization tandem mass spectrometry (ESI-MS-MS), showing a non-monotonous variation along the group (Al > In > Ga). The results reveal a strong covalent character in M-ligand bonding, which allows for through-ligand electron delocalization, and explain the preferred molecular structures of Mq3 complexes as resulting from the interplay between bonding and steric factors. The mer isomer reduces intraligand repulsions, being preferred for smaller metals, while the fac-isomer is favoured for larger metals where stronger covalent M-ligand bonds can be formed due to more extensive through-ligand conjugation mediated by metal "d" orbitals. PMID- 27273192 TI - Comparing mothers' postpartum concerns in two clinical trials 18 years apart. AB - BACKGROUND AND PURPOSE: To determine if U.S. women's postpartum concerns have changed over time. METHODS: Mothers' postpartum concerns were compared in two clinical trials: 1997 (high-risk pregnancy) and 2015 (first-time mothers). Advanced practice nurses (APNs) provided care through 8 weeks postpartum and recorded interactions in clinical logs. Content analysis of logs was used for identifying concerns. RESULTS: Ninety-five percent of 58 1997 mothers were African American; 64% of 62 2015 mothers were Hispanic. The number of infant concerns (129 vs. 144) was similar to four of the top five infant concerns; infant feeding was the top concern for both groups. The 1997 mothers were concerned with body changes, birth control, breastfeeding, maternal health problems, and had more concerns about their health (142 vs. 43); the 2015 mothers were concerned with not having help, fatigue, finding things hard. Both groups had postpartum pain concerns and problems accessing mother/infant governmental programs. CONCLUSIONS: Mothers' concerns regarding infant care were essentially the same over the two time periods with infant feeding as the top concern. Maternal concerns in common were postpartum pain and needing help accessing government programs. Women who had high-risk pregnancies had more health concerns. IMPLICATIONS FOR PRACTICE: Results provide guidance for helping minority mothers in the postpartum period. PMID- 27273195 TI - CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia. AB - Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5 HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID- 27273194 TI - Selective pressure modulation of synaptic voltage-dependent calcium channels involvement in HPNS mechanism. AB - Exposure to hyperbaric pressure (HP) exceeding 100 msw (1.1 MPa) is known to cause a constellation of motor and cognitive impairments named high-pressure neurological syndrome (HPNS), considered to be the result of synaptic transmission alteration. Long periods of repetitive HP exposure could be an occupational risk for professional deep-sea divers. Previous studies have indicated the modulation of presynaptic Ca(2+) currents based on synaptic activity modified by HP. We have recently demonstrated that currents in genetically identified cellular voltage-dependent Ca(2+) channels (VDCCs), CaV 1.2 and CaV 3.2 are selectively affected by HP. This work further elucidates the HPNS mechanism by examining HP effect on Ca(2+) currents in neuronal VDCCs, CaV 2.2 and CaV 2.1, which are prevalent in presynaptic terminals, expressed in Xenopus oocytes. HP augmented the CaV 2.2 current amplitude, much less so in a channel variation containing an additional modulatory subunit, and had almost no effect on the CaV 2.1 currents. HP differentially affected the channels' kinetics. It is, therefore, suggested that HPNS signs and symptoms arise, at least in part, from pressure modulation of various VDCCs. PMID- 27273196 TI - Monte Carlo modelling of photodynamic therapy treatments comparing clustered three dimensional tumour structures with homogeneous tissue structures. AB - We explore the effects of three dimensional (3D) tumour structures on depth dependent fluence rates, photodynamic doses (PDD) and fluorescence images through Monte Carlo radiation transfer modelling of photodynamic therapy. The aim with this work was to compare the commonly used uniform tumour densities with non uniform densities to determine the importance of including 3D models in theoretical investigations. It was found that fractal 3D models resulted in deeper penetration on average of therapeutic radiation and higher PDD. An increase in effective treatment depth of 1 mm was observed for one of the investigated fractal structures, when comparing to the equivalent smooth model. Wide field fluorescence images were simulated, revealing information about the relationship between tumour structure and the appearance of the fluorescence intensity. Our models indicate that the 3D tumour structure strongly affects the spatial distribution of therapeutic light, the PDD and the wide field appearance of surface fluorescence images. PMID- 27273197 TI - Universal amorphous-amorphous transition in GexSe100-x glasses under pressure. AB - Pressure induced structural modifications in vitreous GexSe100-x (where 10 <= x <= 25) are investigated using X-ray absorption spectroscopy (XAS) along with supplementary X-ray diffraction (XRD) experiments and ab initio molecular dynamics (AIMD) simulations. Universal changes in distances and angle distributions are observed when scaled to reduced densities. All compositions are observed to remain amorphous under pressure values up to 42 GPa. The Ge-Se interatomic distances extracted from XAS data show a two-step response to the applied pressure; a gradual decrease followed by an increase at around 15-20 GPa, depending on the composition. This increase is attributed to the metallization event that can be traced with the red shift in Ge K edge energy which is also identified by the principal peak position of the structure factor. The densification mechanisms are studied in details by means of AIMD simulations and compared to the experimental results. The evolution of bond angle distributions, interatomic distances and coordination numbers are examined and lead to similar pressure-induced structural changes for any composition. PMID- 27273198 TI - Effect of pre- and post-partum supplementation with lipid-encapsulated conjugated linoleic acid on milk yield and metabolic status in multiparous high-producing dairy cows. AB - We evaluated the lactation performance, liver lipid content and plasma metabolites indicating the energy balance of dairy cows supplemented with conjugated linoleic acid (CLA) pre- and post-partum (PP) vs. only PP. A total of 60 cows were divided into three groups (n = 20). Daily diet of cows was supplemented with 14 g of CLA (7 g cis-9, trans-11 and 7 g trans-10, cis-12 isomers) from week 3 before the expected date of calving (group CLA1), or from the day of calving (group CLA2) until 77-91 days PP. Control cows were fed an isocaloric, isonitrogenous and isolipidic diet without CLA. Between week 3 and week 6 PP, the milk yield of cows in both CLA-treated groups was approximately 4.5 kg higher (p < 0.05) than in control. Milk fat concentrations decreased from week 3 and were lower in both CLA groups than in control (p < 0.01). Body condition score loss was lower (p < 0.05) in the CLA1 than in the control group on week 5 PP. By week 11 PP, the body condition of both CLA1 and CLA2 groups exceeded that of control. Plasma non-esterified fatty acid was lower in CLA1 compared to CLA2 and control during the early PP period (p < 0.05), while this difference faded away by the late PP period. Beta-hydroxybutyrate (BHBA) increased rapidly in all groups following calving. In CLA1 group, it began to decrease sooner than in CLA2 and control. The prevalence of subclinical ketosis (BHBA > 1.2 mm) was lower in CLA1 group than in CLA2 and control (p < 0.05). Liver biopsy analyses showed that CLA1 treatment decreased (p < 0.05) the total lipid content of liver compared to control at week 5 after calving. Our results show that CLA supplementation is more efficient in alleviating body mass mobilization and decreasing the incidence of subclinical ketosis when applied as early as 3 weeks before calving than started feeding after calving. PMID- 27273199 TI - Role of geographical provenance in the response of silver fir seedlings to experimental warming and drought. AB - Changes in climate can alter the distribution and population dynamics of tree species by altering their recruitment patterns, especially at range edges. However, geographical patterns of genetic diversity could buffer the negative consequences of changing climate at rear range edges where populations might also harbour individuals with drought-adapted genotypes. Silver fir (Abies alba Mill.) reaches its south-western distribution limit in the Spanish Pyrenees, where recent climatic dieback events have disproportionately affected westernmost populations. We hypothesized that silver fir populations from the eastern Pyrenees are less vulnerable to the expected changing climate due to the inclusion of drought-resistant genotypes. We performed an experiment under strictly controlled conditions simulating projected warming and drought compared with current conditions and analysed physiology, growth and survival of silver fir seedlings collected from eastern and western Pyrenean populations. Genetic analyses separated eastern and western provenances in two different lineages. Climate treatments affected seedling morphology and survival of both lineages in an overall similar way: elevated drought diminished survival and induced a higher biomass allocation to roots. Increased temperature and drought provoked more negative stem water potentials and increased delta13C ratios in leaves. Warming reduced nitrogen concentration and increased soluble sugar content in leaves, whereas drought increased nitrogen concentration. Lineage affected these physiological parameters, with western seedlings being more sensitive to warming and drought increase in terms of delta13C, nitrogen and content of soluble sugars. Our results demonstrate that, in A. alba, differences in the physiological response of this species to drought are also associated with differences in biogeographical history. PMID- 27273200 TI - How to Perform Permanent His Bundle Pacing: Tips and Tricks. AB - Right ventricular pacing can cause ventricular dyssynchrony and result in reduced left ventricular systolic function and heart failure. Permanent His bundle pacing is a more physiologic form of pacing, but can be technically challenging. In this article, we describe our technique for permanent His bundle pacing including special considerations and limitations associated with His bundle pacing. PMID- 27273201 TI - [Comment on: Importance of driving pressure for survival of controlled mechanically ventilated ARDS patients]. PMID- 27273202 TI - A Pd-Catalyzed Synthesis of Functionalized Piperidines. AB - A readily available cyclic carbamate 1 functions as a general precursor to a range of functionalized piperidine products via a new Pd-catalyzed annulation strategy. An asymmetric catalytic variant provides a rapid and efficient means to access these heterocycles with high to excellent levels of enantiocontrol. Finally, these richly functionalized compounds are amenable to further chemoselective elaboration. PMID- 27273203 TI - Influence of hydroxyapatite granule size, porosity, and crystallinity on tissue reaction in vivo. Part B: a comparative study with biphasic synthetic biomaterials. AB - OBJECTIVE: The aim of this study was to compare the influence of the physical chemical properties of synthetic hydroxyapatite (HA) and biphasic commercial materials on the biological behavior of study materials through material characterization and SEM analysis before and after application in rabbit tibias. MATERIALS AND METHODS: Two defects were performed in each tibiae for a total of 180 defects: Group I HA granules (2000-4000 MUm), Group II HA granules (1000-2000 MUm), Group III HA granules (600-1000 MUm), Group IV Ossceram(r) nano (Bredent medical GmbH & Co. KG, Senden, Germany), Group V 4Bone(r) granules (MIS Implants Technologies Ltd, Shlomi, Israel), and Group VI: empty defect acted as control. Comparison was performed by mean of material characterization, SEM, and EDX. RESULTS: 4Bone: Pores between 300 MUm and 100 MUm with intra- and interparticle spaces. Ossceram show also interparticle and intraparticle pores, between 100 MUm and 26 MUm, but the proportion of interparticles in the 4Bone is clearly minor than in the Ossceram. Related with pure HA, Group III has the greatest porosity (69.3%). For Group I, the intraparticle pores (0.71 MUm) are about 8 times larger than those of the other two samples. The analysis of the images of in vivo SEM shown as biphasic groups has presented a more gradual resorption of the material. CONCLUSION: HA-based biomaterials, both pure and biphasic, are an effective means for bone regeneration processes; of these, materials with higher initial and secondary porosimetry allow greater cell colonization and therefore more effective substitution by new bone. The two-phase materials have a higher ion release to the environment in the early stages and thus allow greater colonization by collagen fibers that can be matured into new bone. PMID- 27273204 TI - Longitudinal changes in the structure and inflammatory response of the intervertebral disc due to stab injury in a murine organ culture model. AB - Despite the significant public health impact of intervertebral disc (IVD) degeneration and low back pain, it remains challenging to investigate the multifactorial molecular mechanisms that drive the degenerative cascade. Organ culture model systems offer the advantage of allowing cells to live and interact with their native extracellular matrix, while simultaneously reducing the amount of biological variation and complexity present at the organismal level. Murine organ cultures in particular also allow the use of widely available genetically modified animals with molecular level reporters that would reveal insights on the degenerative cascade. Here, we utilize an organ culture system of murine lumbar functional spinal units where we are able to maintain the cellular, metabolic, and structural, and mechanical stability of the whole organ over a 21-day period. Furthermore, we describe a novel approach in organ culture by using tissues from animals with an NF-kappaB-luc reporter in combination with a mechanical injury model, and are able to show that proinflammatory factors and cytokines such as NF kappaB and IL-6 produced by IVD cells can be monitored longitudinally during culture in a stab injury model. Taken together, we utilize a murine organ culture system that maintains the cellular and tissue level behavior of the intervertebral disc and apply it to transgenic animals that allow the monitoring of the inflammatory profile of IVDs. This approach could provide important insights on the molecular and metabolic mediators that regulate the homeostasis of the IVD. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1431-1438, 2016. PMID- 27273205 TI - Reduction of anxiety-like and depression-like behaviors in rats after one month of drinking Aronia melanocarpa berry juice. AB - The treatment of mood and anxiety disorders by nutraceuticals is gaining growing awareness. Berries of Aronia melanocarpa (Black chokeberry) and their extracts, exceptionally abundant in diverse phenolic compounds, have become famous for the highest in vitro antioxidant activity among fruits and notable health benefits (e.g. anti-diabetic, anti-inflammatory, cardioprotective). This study was designed to investigate the behavioral effects of month-long unlimited consumption of Aronia master juice (AJ) and/or juice reconstruct without polyphenols (RJ), in young male rats. AJ was initially evaluated for its content of phenolic compounds by spectrophotometric assays and HPLC-DAD. Rats that were supplied with three various water concentrations of AJ and RJ, respectively: 20% + 0% (ARO group), 5% + 15% (RAJ) and 0 + 20% (PLC), were compared with those which consumed only water (CTL). Daily drinking of AJ solution was significantly elevated from the second or third week onward, which was most expressed in the ARO group. Only this group displayed behavioral variations, manifested by certain hyperactivity in open field tests and prominent reductions of anxiety-like behaviors in the elevated plus maze. The ARO rats also expressed an alleviation of depression-like behavior in forced swimming tests. These findings demonstrate the beneficial behavioral effects of the one-month-long free drinking of phenolic rich AJ in rats (>20 ml per kg b. mass daily) that may be recognized as stimulating, anxiolytic-like and antidepressant-like. The in vitro assays suggested that MAO-A/MAO-B inhibitions by the phenolic compounds of AJ might be the possible in vivo mechanisms for such behavioral actions. PMID- 27273206 TI - Conventional intensive logging promotes loss of organic carbon from the mineral soil. AB - There are few data, but diametrically opposed opinions, about the impacts of forest logging on soil organic carbon (SOC). Reviews and research articles conclude either that there is no effect, or show contradictory effects. Given that SOC is a substantial store of potential greenhouse gasses and forest logging and harvesting is routine, resolution is important. We review forest logging SOC studies and provide an overarching conceptual explanation for their findings. The literature can be separated into short-term empirical studies, longer-term empirical studies and long-term modelling. All modelling that includes major aboveground and belowground biomass pools shows a long-term (i.e. >=300 years) decrease in SOC when a primary forest is logged and then subjected to harvesting cycles. The empirical longer-term studies indicate likewise. With successive harvests the net emission accumulates but is only statistically perceptible after centuries. Short-term SOC flux varies around zero. The long-term drop in SOC in the mineral soil is driven by the biomass drop from the primary forest level but takes time to adjust to the new temporal average biomass. We show agreement between secondary forest SOC stocks derived purely from biomass information and stocks derived from complex forest harvest modelling. Thus, conclusions that conventional harvests do not deplete SOC in the mineral soil have been a function of their short time frames. Forest managers, climate change modellers and environmental policymakers need to assume a long-term net transfer of SOC from the mineral soil to the atmosphere when primary forests are logged and then undergo harvest cycles. However, from a greenhouse accounting perspective, forest SOC is not the entire story. Forest wood products that ultimately reach landfill, and some portion of which produces some soil-like material there rather than in the forest, could possibly help attenuate the forest SOC emission by adding to a carbon pool in landfill. PMID- 27273207 TI - Weyl fermions and spin dynamics of metallic ferromagnet SrRuO3. AB - Weyl fermions that emerge at band crossings in momentum space caused by the spin orbit interaction act as magnetic monopoles of the Berry curvature and contribute to a variety of novel transport phenomena such as anomalous Hall effect and magnetoresistance. However, their roles in other physical properties remain mostly unexplored. Here, we provide evidence by neutron Brillouin scattering that the spin dynamics of the metallic ferromagnet SrRuO3 in the very low energy range of milli-electron volts is closely relevant to Weyl fermions near Fermi energy. Although the observed spin wave dispersion is well described by the quadratic momentum dependence, the temperature dependence of the spin wave gap shows a nonmonotonous behaviour, which can be related to that of the anomalous Hall conductivity. This shows that the spin dynamics directly reflects the crucial role of Weyl fermions in the metallic ferromagnet. PMID- 27273214 TI - An Atomic Force Microscope with Dual Actuation Capability for Biomolecular Experiments. AB - We report a modular atomic force microscope (AFM) design for biomolecular experiments. The AFM head uses readily available components and incorporates deflection-based optics and a piezotube-based cantilever actuator. Jetted polymers have been used in the mechanical assembly, which allows rapid manufacturing. In addition, a FeCo-tipped electromagnet provides high-force cantilever actuation with vertical magnetic fields up to 0.55 T. Magnetic field calibration has been performed with a micro-hall sensor, which corresponds well with results from finite element magnetostatics simulations. An integrated force resolution of 1.82 and 2.98 pN, in air and in DI water, respectively was achieved in 1 kHz bandwidth with commercially available cantilevers made of Silicon Nitride. The controller and user interface are implemented on modular hardware to ensure scalability. The AFM can be operated in different modes, such as molecular pulling or force-clamp, by actuating the cantilever with the available actuators. The electromagnetic and piezoelectric actuation capabilities have been demonstrated in unbinding experiments of the biotin-streptavidin complex. PMID- 27273215 TI - Nanoscale electrodeposition of low-dimensional metal phases and clusters. AB - The present status of the problem of electrochemical formation of low-dimensional metal phases is reviewed. The progress in this field achieved in the last two decades is discussed on the basis of experimental results obtained in selected electrochemical systems with well defined single crystal substrates. The influence of crystallographic orientation and surface inhomogeneities of foreign substrates on the mechanism of formation and the atomic structure of two dimensional (2D) metal phases in the underpotential deposition range is considered. The localized electrodeposition of metal nanoclusters on solid state surfaces applying the STM-tip as a nanoelectrode is demonstrated. PMID- 27273216 TI - Spin-orbit-driven magnetic structure and excitation in the 5d pyrochlore Cd2Os2O7. AB - Much consideration has been given to the role of spin-orbit coupling (SOC) in 5d oxides, particularly on the formation of novel electronic states and manifested metal-insulator transitions (MITs). SOC plays a dominant role in 5d(5) iridates (Ir(4+)), undergoing MITs both concurrent (pyrochlores) and separated (perovskites) from the onset of magnetic order. However, the role of SOC for other 5d configurations is less clear. For example, 5d(3) (Os(5+)) systems are expected to have an orbital singlet with reduced effective SOC. The pyrochlore Cd2Os2O7 nonetheless exhibits a MIT entwined with magnetic order phenomenologically similar to pyrochlore iridates. Here, we resolve the magnetic structure in Cd2Os2O7 with neutron diffraction and then via resonant inelastic X ray scattering determine the salient electronic and magnetic energy scales controlling the MIT. In particular, SOC plays a subtle role in creating the electronic ground state but drives the magnetic order and emergence of a multiple spin-flip magnetic excitation. PMID- 27273217 TI - Topical high potency steroid proclaimed optimal therapy for bullous pemphigoid in the elderly. PMID- 27273219 TI - Multiple cerebral arteriovenous malformations associated to rostral hypoplasia of the superior sagittal sinus: case report. AB - Multiple cerebral arteriovenous malformations (AVMs) are a rare occurrence usually associated with defined genetic disorders or a family history of cerebrovascular disease. The remaining cases cannot be associated to a genetic pathogenesis and are considered idiopathic. We report an extremely unusual case nor genetic neither idiopathic, but linked to an anatomical intracranial venous variation. The patient presented two independent frontal AVMs associated with rostral hypoplasia of the superior sagittal sinus. This anatomical variation may have induced frontal venous hypertension (VHT) triggering the development of the two AVMs. Throughout this intriguing case, we discuss the role of VHT in AVM development. PMID- 27273218 TI - hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress. AB - The maintenance of genome stability is an essential cellular process to prevent the development of diseases including cancer. hSSB1 (NABP2/ OBFC2A) is a critical component of the DNA damage response where it participates in the repair of double-strand DNA breaks and in base excision repair of oxidized guanine residues (8-oxoguanine) by aiding the localization of the human 8-oxoguanine glycosylase (hOGG1) to damaged DNA. Here we demonstrate that following oxidative stress, hSSB1 is stabilized as an oligomer which is required for hSSB1 to function in the removal of 8-oxoguanine. Monomeric hSSB1 shows a decreased affinity for oxidized DNA resulting in a cellular 8-oxoguanine-repair defect and in the absence of ATM signaling initiation. While hSSB1 oligomerization is important for the removal of 8-oxoguanine from the genome, it is not required for the repair of double-strand DNA-breaks by homologous recombination. These findings demonstrate a novel hSSB1 regulatory mechanism for the repair of damaged DNA. PMID- 27273220 TI - Treatment of tumors and metastases of the spine by minimally invasive CAVITY coblation method (plasma field therapy). AB - BACKGROUND: A radical surgery of spine metastases is not possible in many cases, especially by elder multi morbid patients. The modern CAVITY/coblation method offers a very good therapeutic alternative for such patients. The goal of this paper was to evaluate and present the method as well as the results of the treatment of 302 patients with vertebral tumors/metastases. METHODS: Patients with vertebral destructions of the spine caused by spinal tumors and metastases were treated. Diagnosis preoperatively: X-ray, MRT, CT, PET, histology. Tumor tissue resection was carried out by plasma field over the percutaneous transpedicular access and was followed by kyphoplasty. Follow-up with clinical and radiological examinations are in 2, 14 days, 3, 6, 12, 24, 36, 48, 60 months postoperatively. RESULTS: Within 6 years (04/2008-05/2014) 302 patients (188 female, 114 male, age range of 31-92, average age of 65.4 years) were treated. It was shown by all patients: less blood loss, no seriously complications, pain reduction, increase in life quality. Postoperatively was possible: rapid mobilization, immediate radiation and chemotherapy for reduction of the local tumor recurrence rate. CONCLUSIONS: CAVITY has shown itself to be a safe, minimal invasive procedure with good short and long term results, a low complication rate, blood loss and short surgery times. The total local recurrence rate was only 13.5%. Important are: comprehensive diagnostic including tumor staging, correct indication, prognostic assessment, precise surgical technique. PMID- 27273221 TI - The endoscopic endonasal approach for the management of craniopharyngiomas. AB - Craniopharyngiomas are disembryogenetic, benign, tumors that origin from squamous epithelial remnants of Rathke's pouch, developing from any segment of its course, virtually from rhino-pharynx to the hypothalamus. Historically, different microscopic transcranial routes, have been advocated as possible surgical options for the treatment of craniopharyngiomas. The endonasal technique offers a direct approach that permits access to the suprasellar, retrosellar and retroclival space, obviating brain retraction; it provides the advantage of appraoching cranioopharyngiomas without optic nerve manipulation and/or retraction. We herein present the surgical nuances of the endoscopic endonasal approach for the treatment of craniopharyngiomas, highlighting hints, advantages and drawbacks, also in regards of the anatomy dealt with. The endoscopic endonasal technique has been emerging as a viable approach/alternative for the treatment of this disease as the endoscope itself increased its safety and effectiveness. It allows the removal of both infra and supradiaphragmatic lesions - eventually involving the third ventricle chamber but not extending laterally off the ICA out of the visibility and maneuverability of the instruments - avoiding brain and optic nerve manipulation and retraction, with good visualization of the pituitary gland and stalk and the main neurovascular structures. PMID- 27273222 TI - Characterization of the interactions between Escherichia coli receptors, LPS and OmpC, and bacteriophage T4 long tail fibers. AB - Bacteriophages have strict host specificity and the step of adsorption is one of key factors for determining host specificity. Here, we systematically examined the interaction between the Escherichia coli receptors lipopolysaccharide (LPS) and outer membrane protein C (OmpC), and the long tail fibers of bacteriophage T4. Using a variety of LPS mutants, we demonstrated that T4 has no specificity for the sugar sequence of the outer core (one of three LPS regions) in the presence of OmpC but, in the absence of OmpC, can adsorb to a specific LPS which has only one or two glucose residues without a branch. These results strengthen the idea that T4 adsorbs to E. coli via two distinct modes, OmpC-dependent and OmpC-independent, suggested by previous reports (Prehm et al. 1976; Yu and Mizushima 1982). Isolation and characterization of the T4 mutants Nik (No infection to K-12 strain), Nib (No infection to B strain), and Arl (altered recognition of LPS) identified amino acids of the long tail fiber that play important roles in the interaction with OmpC or LPS, suggesting that the top surface of the distal tip head domain of T4 long tail fibers interacts with LPS and its lateral surface interacts with OmpC. PMID- 27273223 TI - First isolation of West Nile virus from a dromedary camel. AB - Although antibodies against West Nile virus (WNV) have been detected in the sera of dromedaries in the Middle East, North Africa and Spain, no WNV has been isolated or amplified from dromedary or Bactrian camels. In this study, WNV was isolated from Vero cells inoculated with both nasal swab and pooled trachea/lung samples from a dromedary calf in Dubai. Complete-genome sequencing and phylogenetic analysis using the near-whole-genome polyprotein revealed that the virus belonged to lineage 1a. There was no clustering of the present WNV with other WNVs isolated in other parts of the Middle East. Within lineage 1a, the dromedary WNV occupied a unique position, although it was most closely related to other WNVs of cluster 2. Comparative analysis revealed that the putative E protein encoded by the genome possessed the original WNV E protein glycosylation motif NYS at E154-156, which contained the N-linked glycosylation site at N-154 associated with increased WNV pathogenicity and neuroinvasiveness. In the putative NS1 protein, the A70S substitution observed in other cluster 2 WNVs and P250, which has been implicated in neuroinvasiveness, were present. In addition, the foo motif in the putative NS2A protein, which has been implicated in neuroinvasiveness, was detected. Notably, the amino-acid residues at 14 positions in the present dromedary WNV genome differed from those in most of the closely related WNV strains in cluster 2 of lineage 1a, with the majority of these differences observed in the putative E and NS5 proteins. The present study is the first to demonstrate the isolation of WNV from dromedaries. This finding expands the possible reservoirs of WNV and sources of WNV infection. PMID- 27273225 TI - Serological and molecular detection of bovine leukemia virus in cattle in Iraq. AB - Bovine leukemia virus (BLV) is highly endemic in many countries, including Iraq, and it impacts the beef and dairy industries. The current study sought to determine the percentage of BLV infection and persistent lymphocytosis (PL) in cattle in central Iraq. Hematological, serological, and molecular observations in cross breeds and local breeds of Iraqi cattle naturally infected with BLV were conducted in the peripheral blood mononuclear cells of 400 cattle (340 cross breed and 60 local breed) using enzyme-linked immunosorbent assay and polymerase chain reaction (PCR). On the basis of the absolute number of lymphocytes, five of the 31 positive PCR cases had PL. Among these leukemic cattle, one case exhibited overt neutrophilia. Serum samples were used to detect BLV antibodies, which were observed in 28 (7%) samples. PCR detected BLV provirus in 31 samples (7.75%). All 28 of the seropositive samples and the 3 seronegative samples were positive using PCR. Associations were observed between bovine leukosis and cattle breed, age and sex. Age-specific analysis showed that the BLV percentage increased with age in both breeds. Female cattle (29 animals; 7.34%) exhibited significantly higher infectivity than male cattle (two animals; 4.34%). In conclusion, comprehensive screening for all affected animals is needed in Iraq; programs that segregate cattle can be an effective and important method to control and/or eliminate the BLV. PMID- 27273224 TI - Presence of a widely disseminated Listeria monocytogenes serotype 4b clone in India. PMID- 27273226 TI - Acardiac twin pregnancies part II: Fetal risk of chorangioma and sacrococcygeal teratoma predicted by pump/acardiac umbilical vein diameters. AB - BACKGROUND: We recently published pump/acardiac umbilical venous diameter (UVD) ratios, representing the pump twin's excess cardiac output fraction, of 27 acardiac twin pregnancies. There was a clear separation between the 17 pump twins that had life-threatening complications and the 10 that did not. The hypothesis of this study is that placental chorangioma and sacrococcygeal teratoma (SCT), tumors whose perfusion also causes high-output complications, have the same fetal outcome as pump twins when perfusion of the tumor requires the same excess cardiac output fraction. METHODS: We compared the three fetoplacental circulations. Fetuses with a placental chorangioma and acardiac twin pregnancies both have their feeding artery and draining vein located at the placental cord insertion. In contrast, SCT lacks a prescribed feeding artery and draining vein. We, therefore, had to modify our model to assume that the diameter of the hypothetical draining vein is related to the flow difference between inferior vena cava and superior vena cava. The latter flow has been estimated sonographically and is the same as the inferior vena cava flow in the absence of an SCT. Furthermore, a simple modification accounts for the different location of the tumor with respect to the placental cord insertion. RESULTS: We propose to apply the clinical pump/acardiac UVD ratios to pregnancies complicated by placental chorangiomas and the modified pump/acardiac UVD ratios for SCT. CONCLUSION: Risk prediction of these rare fetal tumors may be possible based on application of data on excess cardiac output fractions from pump/acardiac UVD ratios and will require future clinical validation. Birth Defects Research (Part A) 106:733-738, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273227 TI - Shape of magnifiers affects controllability in children with visual impairment. AB - PURPOSE: This study aimed to examine the controllability of cylinder-shaped and dome-shaped magnifiers in young children with visual impairment. METHODS: This study investigates goal-directed arm movements in low-vision aid use (stand and dome magnifier-like object) in a group of young children with visual impairment (n = 56) compared to a group of children with normal sight (n = 66). Children with visual impairment and children with normal sight aged 4-8 years executed two types of movements (cyclic and discrete) in two orientations (vertical or horizontal) over two distances (10 cm and 20 cm) with two objects resembling the size and shape of regularly prescribed stand and dome magnifiers. RESULTS: The visually impaired children performed slower movements than the normally sighted children. In both groups, the accuracy and speed of the reciprocal aiming movements improved significantly with age. Surprisingly, in both groups, the performance with the dome-shaped object was significantly faster (in the 10 cm condition and 20 cm condition with discrete movements) and more accurate (in the 20 cm condition) than with the stand-shaped object. CONCLUSION: From a controllability perspective, this study suggests that it is better to prescribe dome-shaped than cylinder-shaped magnifiers to young children with visual impairment. PMID- 27273228 TI - Exploring the Loading Capacity of Generation Six to Eight Dendronized Polymers in Aqueous Solution. AB - Aspects of size, structural (im)perfection, inner density, and guest molecule loading capacity of dendronized polymers (DPs) of high generation (6<=g<=8) in aqueous solution are studied using electron paramagnetic resonance spectroscopy on amphiphilic, spin-labeled guest molecules. The results show that the interior of the charged DPs is strongly polar, especially in comparison to their lower generation (1-4) analogues. This is a direct sign that large amounts of water penetrate the DP surface, reflecting the structural (im)perfections of these high generation DPs and much lower segmental densities than theoretically achievable. Images obtained with atomic force microscopy reveal that the high-generation DPs do not aggregate and give further insights into the structural imperfections. Electron paramagnetic resonance spectroscopic data further show that despite their structural imperfections, these DPs can bind and release large numbers of amphiphilic molecules. It is concluded that attention should be paid to their synthesis, for which a protocol needs to be developed that avoids the relatively large amount of defects generated in the direct conversion of a generation g=4 DP to a generation g=6 DP, which had to be used here. PMID- 27273230 TI - Lignin Valorization through Catalytic Lignocellulose Fractionation: A Fundamental Platform for the Future Biorefinery. AB - Current processes for the fractionation of lignocellulosic biomass focus on the production of high-quality cellulosic fibers for paper, board, and viscose production. The other fractions that constitute a major part of lignocellulose are treated as waste or used for energy production. The transformation of lignocellulose beyond paper pulp to a commodity (e.g., fine chemicals, polymer precursors, and fuels) is the only feasible alternative to current refining of fossil fuels as a carbon feedstock. Inspired by this challenge, scientists and engineers have developed a plethora of methods for the valorization of biomass. However, most studies have focused on using one single purified component from lignocellulose that is not currently generated by the existing biomass fractionation processes. A lot of effort has been made to develop efficient methods for lignin depolymerization. The step to take this fundamental research to industrial applications is still a major challenge. This review covers an alternative approach, in which the lignin valorization is performed in concert with the pulping process. This enables the fractionation of all components of the lignocellulosic biomass into valorizable streams. Lignocellulose fractions obtained this way (e.g., lignin oil and glucose) can be utilized in a number of existing procedures. The review covers historic, current, and future perspectives, with respect to catalytic lignocellulose fractionation processes. PMID- 27273231 TI - Experimental study in pulmonary artery sealing with a vessel-sealing device. AB - BACKGROUND: The development of vessel-sealing devices will facilitate safety in video-assisted thoracoscopic surgery. Our objective was to evaluate the feasibility and safety of sealing pulmonary arteries with the Enseal tissue sealing device. METHODS: Pulmonary arteries from beagle dogs (mean body weight 13.1 kg, range 10.5-15.4 kg) were divided into 3 groups according to the in-vivo sealing method used (Enseal, ligation, and proximal ligation plus distal Enseal) and extracted to evaluate the pressure tolerance up to 75 mm Hg at the sealed end. A left lower lobectomy was performed to evaluate chronic-phase durability of the sealed stumps in a survival model. Two or three branches of the pulmonary arteries in each dog were allocated to each of the 3 groups. After the scheduled survival period, the pulmonary arteries were sampled. RESULTS: Pressure tolerance at the sealed end was evaluated in 91 pulmonary artery sections. All sealed ends showed pressure tolerance >75 mm Hg. A left lower lobectomy was performed in 13 dogs in which 35 pulmonary artery sections had been allocated into the 3 groups. No sealing failure was found, and pathological findings showed healing and persistent hemostasis at all sealed ends of the pulmonary arteries after 2 and 4 weeks of the survival period. CONCLUSIONS: Pulmonary arteries sealed in vivo with the Enseal device showed pressure tolerance >75 mm Hg in the acute phase, and persistent hemostasis after 2 or 4 weeks. Pulmonary artery sealing with the Enseal device is feasible and safe in thoracic surgery settings. PMID- 27273232 TI - Neglected foreign body aspiration mimicking bronchial carcinoma. AB - Foreign body aspiration can occur in any age group, but it is more commonly seen in children. In adults, there is usually a predisposing condition that poses a risk of aspiration. If aspiration occurs, prompt diagnosis and extraction of the foreign body is needed to prevent early and late complications. We report a rare case of neglected foreign body aspiration in a 45-year-old schizophrenic opium addicted patient, which resulted in an occlusive lesion in the bronchus, mimicking bronchial carcinoma. PMID- 27273229 TI - Tumor testing to identify lynch syndrome in two Australian colorectal cancer cohorts. AB - BACKGROUND AND AIM: Tumor testing of colorectal cancers (CRC) for mismatch repair (MMR) deficiency is an effective approach to identify carriers of germline MMR gene mutation (Lynch syndrome). The aim of this study was to identify MMR gene mutation carriers in two cohorts of population-based CRC utilizing a combination of tumor and germline testing approaches. METHODS: Colorectal cancers from 813 patients diagnosed with CRC < 60 years of age from the Australasian Colorectal Cancer Family Registry (ACCFR) and from 826 patients from the Melbourne Collaborative Cohort Study (MCCS) were tested for MMR protein expression using immunohistochemistry, microsatellite instability (MSI), BRAFV600E somatic mutation, and for MLH1 methylation. MMR gene mutation testing (Sanger sequencing and Multiplex Ligation Dependent Probe Amplification) was performed on germline DNA of patients with MMR-deficient tumors and a subset of MMR-proficient CRCs. RESULTS: Of the 813 ACCFR probands, 90 probands demonstrated tumor MMR deficiency (11.1%), and 42 had a MMR gene germline mutation (5.2%). For the MCCS, MMR deficiency was identified in the tumors of 103 probands (12.5%) and seven had a germline mutation (0.8%). All the mutation carriers were diagnosed prior to 70 years of age. Probands with a MMR-deficient CRC without MLH1 methylation and a gene mutation were considered Lynch-like and comprised 41.1% and 25.2% of the MMR deficient CRCs for the ACCFR and MCCS, respectively. CONCLUSIONS: Identification of MMR gene mutation carriers in Australian CRC-affected patients is optimized by immunohistochemistry screening of CRC diagnosed before 70 years of age. A significant proportion of MMR-deficient CRCs will have unknown etiology (Lynch like) proving problematic for clinical management. PMID- 27273233 TI - Post-cardiotomy open chest management. A single-unit experience. AB - OBJECTIVE: Post-cardiotomy open chest management is used either for salvage or as a planned therapeutic option in patients with low cardiac output, hemorrhage, or intractable arrhythmias. We reviewed our experience with these patients. METHODS: Over a 3-year period, 2534 adult cardiac patients were operated on and 35 (1.4%) had delayed sternal closure. The median age was 72 years (range 46-86 years) and mean logistic EuroSCORE I was 11.29 (range 1.33-84.99). The patients were divided into two groups: group A (22/35, 62.9%) left the operating room without sternal closure due to hemodynamic instability after coming off cardiopulmonary bypass; group B (13/35, 37.1%) had a resternotomy and sternal closure was delayed due to acute deterioration in the cardiac intensive care unit. RESULTS: The median intensive care unit stay was 17 days (range 2-70 days). Mortality was 25.7% (9 patients). All survivors were followed-up for at least 2 years, with a 2-year survival rate of 57.1%. Overall mortality was broadly similar in both groups. There was a high rate of postoperative complications in both groups, including chest sepsis (77%), liver failure (14.3), renal failure requiring renal replacement therapy (42.9%), sternal wound infection (28.6%), gut ischemia (2.9%), cerebrovascular accident (11.4), and multiorgan failure (31.4%). CONCLUSIONS: Some may argue that open chest management is an acceptable salvage procedure, however, follow-up demonstrated significant adverse cardiac or cerebrovascular events in a short period following discharge, thus delayed sternal closure is really a salvage procedure but useful in centers without access to extracorporeal membrane oxygenation. PMID- 27273234 TI - Mind the gap: fetal physiology from bench to bedside. PMID- 27273235 TI - Brain mesenchymal stem cells: physiology and pathological implications. AB - Mesenchymal stem cells (MSCs) are defined as progenitor cells that give rise to a number of unique, differentiated mesenchymal cell types. This concept has progressively evolved towards an all-encompassing concept including multipotent perivascular cells of almost any tissue. In central nervous system, pericytes are involved in blood-brain barrier, and angiogenesis and vascular tone regulation. They form the neurovascular unit (NVU) together with endothelial cells, astrocytes and neurons. This functional structure provides an optimal microenvironment for neural proliferation in the adult brain. Neurovascular niche include both diffusible signals and direct contact with endothelial and pericytes, which are a source of diffusible neurotrophic signals that affect neural precursors. Therefore, MSCs/pericyte properties such as differentiation capability, as well as immunoregulatory and paracrine effects make them a potential resource in regenerative medicine. PMID- 27273237 TI - Characteristics of Decedents in Medicare Advantage and Traditional Medicare. PMID- 27273236 TI - Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3. AB - Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273238 TI - Oviposition of Culex tarsalis (Diptera: Culicidae) Differs on Water Conditioned by Potential Fish and Insect Predators. AB - The response of egg-laying Culex tarsalis Coquillett (Diptera: Culicidae) to water conditioned by three fish species used for mosquito control and three predatory aquatic insect species was examined in laboratory binary choice experiments. Oviposition by Cx. tarsalis was 72% less on water conditioned with the arroyo chub, Gila orcutti (Eigenmann & Eigenmann) (Cypriniformes: Cyprinidae) relative to control cups containing aged tap water, but no significant difference was found in the numbers of egg rafts laid on water conditioned with the fathead minnow (Pimephales promelas (Rafinesque), Cypriniformes: Cyprinidae) and the control treatment (water aged 24 h). Mosquito oviposition on water conditioned with the predominantly herbivorous/algivorous California Mozambique tilapia hybrid (Oreochromis mossambicus (Peters) * Oreochromis urolepis hornorum L. (Perciformes: Cichlidae)) or predatory insects (nymphs: Sympetrum corruptum (Hagen) (Odonata: Libellulidae); adults: Thermonectus basillaris (Harris) or Cybister fimbriolatus (Say) (Coleoptera: Dytiscidae)) did not differ significantly relative to that onto water aged for 24 h. As compared with water aged 24 h and water conditioned with diving beetles, oviposition by Cx. tarsalis was significantly lower (>=53%) when live predatory diving beetles were present in oviposition cups. Gravid Cx. tarsalis females do not respond equally to putative semiochemicals in water conditioned with the piscine or aquatic insect predators of immature mosquitoes tested here. PMID- 27273240 TI - Erratum. PMID- 27273239 TI - TrapTech R-Octenol Lure Does Not Improve the Capture Rates of Aedes albopictus (Diptera: Culicidae) and Other Container-Inhabiting Species in Biogents Sentinel Traps. AB - Aedes albopictus (Skuse) and other container-inhabiting species have become important public health concerns due to the transmission of dengue, chikungunya, and Zika viruses. Effective surveillance is dependent on the ability to collect a sufficient number of mosquitoes for population monitoring and pathogen isolation. The Biogents Sentinel (BGS) trap supplied with a proprietary human skin lure has become the standard tool for container-inhabiting Aedes species collections worldwide. Recently, R-octenol, a single isomer of the well characterized mosquito attractant octenol, was shown to greatly improve the capture rate of some Aedes species when utilized with the Center for Disease Control and Prevention (CDC) light traps and Mosquito Magnet traps. This study evaluated the effectiveness of the TrapTech lure (TT lure), containing R-octenol, alone or in combination with the human skin lure in a BGS trap to capture Ae. albopictus and other species. BGS traps with human skin lures or a combination of the two lures collected approximately twice as many Ae. albopictus females compared to those with TT lures. Unlike previous studies, baiting BGS traps with TT lures did not result in increased diversity of mosquito species, or in higher numbers of other container-inhabiting Aedes species. Although human skin lures were clearly superior to TT R-octenol lures in BGS traps, R-octenol lures are more widely available and might still be used as an alternative lure, especially when Ae. albopictus populations are high. PMID- 27273241 TI - Development of a comprehensive Blast-Related Auditory Injury Database (BRAID). AB - The Department of Defense Hearing Conservation Program provides specific guidance for service components to prevent occupational hearing loss; however, it does not specifically contend with the unique noise exposures observed in the theater of war, such as blasts and explosions. In order to examine the effects of blast injury on hearing sensitivity, we developed a large database composed of demographic, audiometric, point of injury, and medical outcome data, with the primary aim of developing a long-standing and integrated capability for the surveillance, assessment, and investigation of blast-related hearing outcomes. Methods used to develop the dataset are described. Encompassing more than 16,500 Navy and Marine Corps personnel, the Blast-Related Auditory Injury Database (BRAID) includes individuals with a blast-related injury and nonblast control subjects. Using baseline and postdeployment hearing threshold data, a retrospective analysis of the cohort revealed that the rate of hearing loss for the injured servicemembers was 39%. The BRAID will be useful for studies that assess hearing patterns following deployment-related injury, such as blast exposures, that facilitate exploration of health outcomes and whether they are predictive of audiometric disposition and that help establish hearing loss prevention strategies and program policies for affected military commands and servicemembers. PMID- 27273242 TI - Risk of skin cancer in patients on chronic haemodialysis: a nationwide, population-based study in Taiwan. AB - BACKGROUND: Patients on chronic haemodialysis (HD) have a higher incidence of cancer. However, the risk of skin cancer in this population has rarely been investigated. OBJECTIVES: To investigate the risk of nonmelanoma skin cancer (NMSC) and cutaneous melanoma in patients on chronic HD and to explore the associated risk factors. METHODS: We performed retrospective cohort and nested case-control studies using records in the Taiwanese National Health Insurance Research Database between 1999 and 2013. The HD cohort included 79 668 incident patients on HD, for whom the standardized incidence ratios (SIRs) for incident NMSC and cutaneous melanoma were determined. In the nested case-control study, patients on HD with NMSC were matched to those without skin cancers. The impact of various factors on the development of NMSC was determined by conditional logistic regression analysis. RESULTS: Among the 79 668 patients on HD, 248 cases of NMSC and 22 cases of cutaneous melanoma occurred after a mean 4.95 years of follow-up. The SIRs for NMSC and cutaneous melanoma in patients on HD were 1.58 (95% confidence interval 1.39-1.79) and 1.44 (95% confidence interval 0.91-2.19), respectively. Of the patients on HD, a higher risk of NMSC was found in men (1.5 fold), South Taiwan residents (twofold) and patients with uraemic pruritus after long-term antihistamine treatment (1.53-fold). However, the incidence of NMSC was not increased in patients with uraemic pruritus receiving ultraviolet B phototherapy. CONCLUSIONS: Patients on chronic HD are at higher risk of NMSC. Uraemic pruritus further increases the risk of NMSC, which might be prevented by ultraviolet B phototherapy. PMID- 27273243 TI - iTRAQ-based quantitative proteomic analysis reveals potential factors associated with the enhancement of phenazine-1-carboxamide production in Pseudomonas chlororaphis P3. AB - Phenazine-1-carboxamide (PCN), a phenazine derivative, is strongly antagonistic to fungal phytopathogens. Pseudomonas chlororaphis HT66 is a PCN-producing, non pathogenic biocontrol strain, and we obtained the mutant P. chlororaphis P3, which produces 4.7 times more PCN than the wild-type HT66 strain. To reveal the cause of PCN production enhancement in P3 and find potential factors related to PCN biosynthesis, an iTRAQ-based quantitative proteomic analysis was used to study the expression changes between the two strains. Of the 452 differentially expressed proteins, most were functionally mapped into PCN biosynthesis pathway or other related metabolisms. The upregulation of proteins, including PhzA/B, PhzD, PhzF, PhzG, and PhzH, involved in PCN biosynthesis was in agreement with the efficient production of PCN in P3. A number of proteins that function primarily in energy production, amino acid metabolism, and secondary metabolism played important roles in PCN biosynthesis. Notably, proteins involved in the uptake and conversion of phosphate, inorganic nitrogen sources, and iron improved the PCN production. Furthermore, the type VI secretion system may participate in the secretion or/and indirect biosynthetic regulation of PCN in P. chlororaphis. This study provides valuable clues to better understand the biosynthesis, excretion and regulation of PCN in Pseudomonas and also provides potential gene targets for further engineering high-yield strains. PMID- 27273244 TI - Potential accuracy of navigated K-wire guided supra-acetabular osteotomies in orthopedic surgery: a CT fluoroscopy cadaver study. AB - BACKGROUND: The aim of this study was to evaluate the accuracy of supra acetabular pelvic tumor resections in human, full-body cadavers and under realistic operation room conditions with the help of a navigation system and K wires as guidance for the oscillating saw. METHODS: Seven hemipelvises from fresh, human, male, full-body cadavers were used. A preoperative and a postoperative CT was performed. Under control of the navigation system K-wires were inserted and served as guidance for the oscillating saw to reduce the error by vibration and jerking movements. The accuracy of the computer aided resections was compared with the accuracy of freehand resections in customized 3D printed pelvises with geometries identical to the cadavers used. RESULTS: The mean deviation of the navigated osteotomies was 1.9 mm (standard deviation 1.0 mm) significantly (P < 0.001) lower than the mean deviation of freehand osteotomies at 9.2 mm (standard deviation 3.7 mm). CONCLUSION: Navigated K-wires for supra acetabular osteotomies allow significantly higher accuracy than freehand procedures under simulated operation room conditions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273245 TI - A systematic diagnostic and therapeutic approach for the treatment of patients after cardio-pulmonary resuscitation: a prospective evaluation of 212 patients over 5 years. AB - A literature on systematic treatment protocols for patients after resuscitation for cardiac arrest is lacking. We evaluated a systematic protocol, including ECG, echocardiogram, urgent cardiac catheterisation ("STEMI-like" workflow), CT scans, laboratory findings, IABP, hypothermia, and cMRI, prospectively over 5 years. The primary endpoint was the Cerebral Performance Category Scale (CPCS). During the period from January 2008 to December 2012, 212 patients were included. The mean age was 66.7 years, n = 151 (71.2 %) were male, mean time from the first medical contact to start of catheterisation was 76.6 min, and ventricular fibrillation (VF) was present in n = 99 (46.7 %). A significant coronary artery stenosis was seen in n = 130 (61.3 %), PCI was performed in n = 101 (47.6 %), an ACS was found in n = 100 (47.2 %), n = 91 patients (42.9 %) had another cardiac cause, an extra cardiac cause was found in n = 12 (5.7 %, mostly a cerebral process), and in 9 patients (4.3 %), no cause was identifiable. A significant difference in mortality was found for patients with TIMI flow 2/3 vs. 0/1 (65.4 vs. 95.7 %, p < 0.01). The difference of intra-aortic balloon pumping vs. no pumping was not significant, performing hypothermia reduced mortality significantly (52.7 vs. 68.2 %, p = 0.04). The survival rate was n = 76 (35.9 %), a CPCS of 1/2 was reached in n = 68 pts (32.1 %), patients with ongoing resuscitation had a 100 % mortality (n = 41), and VF had a lower mortality (54.6 vs. 72.6 %, p < 0.01). A systematic algorithm may improve the outcome of patients after reanimation compared with classically reported outcomes. The data are hypothesis generating for further studies. PMID- 27273246 TI - The personal experience of living with chronic heart failure: a qualitative meta synthesis of the literature. AB - AIMS AND OBJECTIVES: To determine, from a systematic literature review, the experience of living with heart failure and to propose some practice guidelines and research questions. BACKGROUND: Chronic heart failure has been one of the fastest growing illnesses in recent decades, with almost 23 million people affected worldwide. This complex syndrome has multiple causes and appears when underlying heart disease is advanced. Currently, heart failure has no cure and leads to a significant deterioration in patients' quality of life. DESIGN: Qualitative meta-synthesis. METHODS: A qualitative meta-synthesis was conducted to extract and analyse qualitative research from the Cochrane, PubMed, CINAHL, PsycINFO, Web of Science and Cuiden databases. Snowball sampling and a manual search were performed to identify other relevant studies. RESULTS: Twenty-five qualitative studies were selected. The findings indicate that there are three main themes that describe the phenomenon. The first theme refers to the experiences related to the beginning of the process. The second theme is connected with the effects on the person: physical, emotional, social and spiritual changes. The third theme is linked with how to live with heart failure despite the illness, including the adjustment and coping process and how external resources can help them to manage. CONCLUSIONS: Heart failure has a major impact on the entire person, but some areas have not been addressed. By creating new tools to understand and evaluate the impact of this illness and interventions that prevent or improve some situations, we can promote the well-being and the quality of life of this population. RELEVANCE TO CLINICAL PRACTICE: Nurses must have a personal knowledge of the experiences and needs of the patients. To do this, nurses should create care environments that promote an exchange of experiences and knowledge between the nurse and the patient and family. PMID- 27273247 TI - Unveiling the Pathways of Dioxygen Through the C2 Component of the Environmentally Relevant Monooxygenase p-Hydroxyphenylacetate Hydroxylase from Acinetobacter baumannii: A Molecular Dynamics Investigation. AB - In this work, models of the homotetrameric C2 component of the monooxygenase p hydroxyphenylacetate hydroxylase from Acinetobacter baumannii, in complex with dioxygen (O2 ) and, or not, the substrate p-hydroxyphenylacetate (HPA) were built. Both models proved to be amenable to random-acceleration molecular dynamics (RAMD) simulations, whereby a tiny randomly oriented external force, acting on O2 at the active site in front of flavin mononucleotide (FMNH(-) ), accelerated displacement of O2 toward the bulk solvent. This allowed us to carry out a sufficiently large number of RAMD simulations to be of statistical significance. The two systems behaved very similarly under RAMD, except for O2 leaving the active site more easily in the absence of HPA, but then finding similar obstacles in getting to the gate as when the active site was sheltered by HPA. This challenges previous conclusions that HPA can only reach the active center after that the C4aOOH derivative of FMNH(-) is formed, requiring uptake of O2 at the active site before HPA. According to these RAMD simulations, O2 could well get to FMNH(-) also in the presence of the substrate at the active site. PMID- 27273248 TI - Pharmacokinetic Interaction Between Isavuconazole and a Fixed-Dose Combination of Lopinavir 400 mg/Ritonavir 100 mg in Healthy Subjects. AB - This phase 1, open-label study evaluated the pharmacokinetic effects of coadministration of the antifungal agent, isavuconazole (administered as its water-soluble prodrug isavuconazonium sulfate), with the antiretroviral agent lopinavir/ritonavir in healthy adults. In part 1, 13 subjects were randomized to 2 arms to receive multiple doses of oral isavuconazole 100 mg either alone or with lopinavir/ritonavir 400/100 mg. In part 2, a different group of 55 subjects were randomized to 3 arms to receive multiple doses of oral isavuconazole 200 mg, either alone or with lopinavir/ritonavir 400/100 mg, or to receive oral lopinavir/ritonavir 400/100 mg alone. Mean area under the concentration-time curve (AUC) following the last dose (AUCtau ) and Cmax of isavuconazole increased by 113% and 96% in part 1 and by 96% and 74% in part 2 in the presence vs absence of lopinavir/ritonavir, respectively. Mean AUCtau and Cmax of lopinavir were 27% and 23% lower, and mean AUCtau and Cmax of ritonavir were 31% and 33% lower in the presence vs absence of isavuconazole, respectively. Mild to moderate gastrointestinal disorders were the most common adverse events experienced. These findings indicate that coadministration of lopinavir/ritonavir with isavuconazole can decrease the exposure of lopinavir/ritonavir and increase the exposure of isavuconazole. Patients should be monitored for reduced antiviral efficacy if these agents are coadministered. PMID- 27273249 TI - Practical and Broadly Applicable Catalytic Enantioselective Additions of Allyl B(pin) Compounds to Ketones and alpha-Ketoesters. AB - A set of broadly applicable methods for efficient catalytic additions of easy-to handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic alpha ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3 ) results in much higher enantioselectivity. With alpha-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well. PMID- 27273252 TI - The rise of organic electrode materials for energy storage. AB - Organic electrode materials are very attractive for electrochemical energy storage devices because they can be flexible, lightweight, low cost, benign to the environment, and used in a variety of device architectures. They are not mere alternatives to more traditional energy storage materials, rather, they have the potential to lead to disruptive technologies. Although organic electrode materials for energy storage have progressed in recent years, there are still significant challenges to overcome before reaching large-scale commercialization. This review provides an overview of energy storage systems as a whole, the metrics that are used to quantify the performance of electrodes, recent strategies that have been investigated to overcome the challenges associated with organic electrode materials, and the use of computational chemistry to design and study new materials and their properties. Design strategies are examined to overcome issues with capacity/capacitance, device voltage, rate capability, and cycling stability in order to guide future work in the area. The use of low cost materials is highlighted as a direction towards commercial realization. PMID- 27273251 TI - Low molecular weight glutenin subunit gene Glu-B3h confers superior dough strength and breadmaking quality in wheat (Triticum aestivum L.). AB - Low molecular weight glutenin subunit is one of the important quality elements in wheat (Triticum aestivum L.). Although considerable allelic variation has been identified, the functional properties of individual alleles at Glu-3 loci are less studied. In this work, we performed the first comprehensive study on the molecular characteristics and functional properties of the Glu-B3h gene using the wheat cultivar CB037B and its Glu-B3 deletion line CB037C. The results showed that the Glu-B3h deletion had no significant effects on plant morphological or yield traits, but resulted in a clear reduction in protein body number and size and main quality parameters, including inferior mixing property, dough strength, loaf volume, and score. Molecular characterization showed that the Glu-B3h gene consists of 1179 bp, and its encoded B-subunit has a longer repetitive domain and an increased number of alpha-helices, as well as higher expression, which could contribute to superior flour quality. The SNP-based allele-specific PCR markers designed for the Glu-B3h gene were developed and validated with bread wheat holding various alleles at Glu-B3 locus, which could effectively distinguish the Glu-B3h gene from others at the Glu-B3 locus, and have potential applications for wheat quality improvement through marker-assisted selection. PMID- 27273253 TI - A New Versatile Water-Soluble Iniferter Platform for the Preparation of Molecularly Imprinted Nanoparticles by Photopolymerisation in Aqueous Media. AB - The multi-step synthesis of a new water-soluble dithiocarbamate iniferter platform for the preparation of nanoparticles and -gels in aqueous solvents by photoinduced living-radical polymerisation is described herein. The water solubility of the dithiocarbamate iniferter was achieved by incorporating two unprotected glucose units into the iniferter structure by copper(I)-catalysed azide-alkyne cycloaddition ("click chemistry"). Molecularly imprinted nanoparticles (MIPs) specific for 2,4-dichlorophenoxyacetic acid and the corresponding non-imprinted particles (NIPs) were prepared in pure water by using the prepared iniferter as photoinitiator. Radioligand binding tests confirmed a high imprinting factor, and the living character of the iniferter was demonstrated by re-initiating a second photochemical polymerisation on the NIP nanoparticles in water by using ethylene glycol methacrylate phosphate. Our newly synthesised structure is a promising tool for iniferter-mediated photopolymerisations in aqueous media for the preparation of biocompatible nanomaterials with high potential for biomedical applications in a bottom-up fashion. PMID- 27273255 TI - Ultrafast-Contactless Flash Sintering using Plasma Electrodes. AB - This paper presents a novel derivative of flash sintering, in which contactless flash sintering (CFS) is achieved using plasma electrodes. In this setup, electrical contact with the sample to be sintered is made by two arc plasma electrodes, one on either side, allowing current to pass through the sample. This opens up the possibility of continuous throughput flash sintering. Preheating, a usual precondition for flash sintering, is provided by the arc electrodes which heat the sample to 1400 degrees C. The best results were produced with pre compacted samples (bars 1.8 mm thick) of pure B4C (discharge time 2s, current 4A) and SiC:B4C 50 wt% (3s at 6A), which were fully consolidated under a heating rate approaching 20000 degrees C/min. For the composite a cylindrical volume of 14 mm(3) was sintered to full density with limited grain growth. PMID- 27273254 TI - Tuning the Selectivity of Biodegradable Antimicrobial Cationic Polycarbonates by Exchanging the Counter-Anion. AB - There is a growing interest in modern healthcare to develop systems able to fight antibiotic resistant bacteria. Antimicrobial cationic biodegradable polymers able to mimic antimicrobial peptides have shown to be effective against both Gram positive and Gram-negative bacteria. In these systems, the hydrophilic hydrophobic ratio and the cationic charge density play a pivotal role in defining the killing efficiency. Nevertheless, many of these antimicrobial polymers show relatively low selectivity as defined by the relative toxicity to mammalian cells or hemolysis relative to pathogens. In this study, a series of polycarbonates containing pendant quaternary ammoniums are used to understand the role of different counter-anions including chloride, citrate, malonate, benzoate, acetate, lactate and trifluoroacetate, and the antibiotic penicillin on antimicrobial efficacy and selectivity. Interestingly, it is found that in spite of the strong antimicrobial activity of trifluoroacetate and benzoate anions, they prove to be much less hemolytic than chloride anion. It is believed that the proper selection of the anion could enhance the potential of antimicrobial polymers to fight against clinically relevant pathogenic infections, while concurrently mitigating harmful side effects. PMID- 27273256 TI - Does the weekend effect influence the length of stay in patients admitted with tonsillitis, quinsy and epistaxis? A review of 363 emergency admissions over a 12 month period. PMID- 27273258 TI - Comparisons in childhood obesity and cardiometabolic risk factors among urban Saudi Arab adolescents in 2008 and 2013. AB - BACKGROUND: We aimed to compare the prevalence of childhood obesity and other cardiometabolic risk factors from two independent cohorts (2008 and 2013) in Riyadh, Saudi Arabia. METHODS: A total of 4549 adolescents aged 12-18 years [2454 boys, 2095 girls], taken from two independent cohorts, 5 years apart (2008 and 2013), were included. Anthropometrics were measured, and fasting blood samples were taken to ascertain glucose and lipid profile. RESULTS: The overall prevalence of obesity was significantly higher in 2013 [15.3 (95% confidence interval 13.7-16.9)] than 2008 [12.6 (11.3-13.9)] (P = 0.012). Stratified by sex, the prevalence of obesity among boys was significantly higher in 2013 than 2008 [2008 = 12.0 (10.3-13.7) versus 2013 = 17.4 (15.1-19.7); P < 0.001]. The age groups 13 and 15 years had a significantly higher mean triglycerides in 2013 than 2008 (P-values 0.003 and <0.001, respectively) and lower mean HDL-cholesterol also in the 13 years old age group (P < 0.001). CONCLUSIONS: The prevalence of childhood obesity in Saudi Arabia has increased in particular age groups (13-15 years) during a 5-year span. Special attention is warranted in these vulnerable age groups, particularly in boys, as cardiometabolic risk factors appear to worsen. PMID- 27273257 TI - Thyrostimulin-TSHR signaling promotes the proliferation of NIH:OVCAR-3 ovarian cancer cells via trans-regulation of the EGFR pathway. AB - Gonadotropin signaling plays an indispensable role in ovarian cancer progression. We previously have demonstrated that thyrostimulin and thyroid-stimulating hormone receptor (TSHR), the most ancient glycoprotein hormone and receptor pair that evolved much earlier than the gonadotropin systems, co-exist in the ovary. However, whether thyrostimulin-driven TSHR activation contributes to ovarian cancer progression in a similar way to gonadotropin receptors has never been explored. In this study, we first found that TSHR is expressed in both rat normal ovarian surface epithelium and human epithelial ovarian cancers (EOCs). Using human NIH:OVCAR-3 as a cell model, we demonstrated that thyrostimulin promotes EOC cell proliferation as strongly as gonadotropins. Thyrostimulin treatment not only activated adenylyl cyclase and the subsequent PKA, MEK-ERK1/2 and PI3K-AKT signal cascades, but also trans-activated EGFR signaling. Signaling dissection using diverse inhibitors indicated that EOC cell proliferation driven by thyrostimulin-TSHR signaling is PKA independent, but does require the involvement of the MEK-ERK and PI3K-AKT signal cascades, which are activated mainly via the trans-activation of EGFR. Thus, not only have we proved that this ancient glycoprotein hormone system is involved in NIH:OVCAR-3 cell proliferation for the first time, but also that it may possibly become a novel oncotarget when studying ovarian cancer. PMID- 27273259 TI - Nonuniform allocation of hippocampal neurons to place fields across all hippocampal subfields. AB - The mechanisms governing how the hippocampus selects neurons to exhibit place fields are not well understood. A default assumption in some previous studies was the uniform random draw with replacement (URDWR) model, which, theoretically, maximizes spatial "pattern separation", and predicts a Poisson distribution of the numbers of place fields expressed by a given cell per unit area. The actual distribution of mean firing rates exhibited by a population of hippocampal neurons, however, is approximately exponential or log-normal in a given environment and these rates are somewhat correlated across multiple places, at least under some conditions. The advantage of neural activity-dependent immediate early gene (IEG) analysis, as a proxy for electrophysiological recording, is the ability to obtain much larger samples of cells, even those whose activity is so sparse that they are overlooked in recording studies. Thus, a more accurate representation of the activation statistics can potentially be achieved. Some previous IEG studies that examined behavior-driven IEG expression in CA1 appear to support URDWR. There was, however, in some of the same studies, an under recruitment of dentate gyrus granule cells, indicating a highly skewed excitability distribution, which is inconsistent with URDWR. Although it was suggested that this skewness might be related to increased excitability of recently generated granule cells, we show here that CA1, CA3, and subiculum also exhibit cumulative under-recruitment of neurons. Thus, a highly skewed excitability distribution is a general principle common to all major hippocampal subfields. Finally, a more detailed analysis of the frequency distributions of IEG intranuclear transcription foci suggests that a large fraction of hippocampal neurons is virtually silent, even during sleep. Whether the skewing of the excitability distribution is cell-intrinsic or a network phenomenon, and the degree to which this excitability is fixed or possibly time-varying are open questions for future studies. (c) 2016 Wiley Periodicals, Inc. PMID- 27273260 TI - Design, biological evaluation and 3D QSAR studies of novel dioxin-containing pyrazoline derivatives with thiourea skeleton as selective HER-2 inhibitors. AB - A series of novel dioxin-containing pyrazoline derivatives with thiourea skeleton have been designed, synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. A majority of them displayed selective HER-2 inhibitory activity against EGFR inhibitory activity. Compound C20 displayed the most potent activity against HER-2 and MDA-MB-453 human breast cancer cell line (IC50 = 0.03 MUM and GI50 = 0.15 MUM), being slightly more potent than the positive control Erlotinib (IC50 = 0.16 MUM and GI50 = 1.56 MUM) and comparable with Lapatinib (IC50 = 0.01 MUM and GI50 = 0.03 MUM). It is a more exciting result that C20 was over 900 times more potent against HER-2 than against EGFR while this value was 0.19 for Erlotinib and 1.00 for Lapatinib, indicating high selectivity. The results of docking simulation indicate that the dioxin moiety occupied the exit of the active pocket and pushed the carbothioamide deep into the active site. QSAR models have been built with activity data and binding conformations to begin our work in this paper as well as to provide a reliable tool for reasonable design of EGFR/HER-2 inhibitors in future. PMID- 27273250 TI - A semi-mechanism approach based on MRI and proteomics for prediction of conversion from mild cognitive impairment to Alzheimer's disease. AB - Mild cognitive impairment (MCI) is a precursor phase of Alzheimer's disease (AD). As current treatments may be effective only at the early stages of AD, it is important to track MCI patients who will convert to AD. The aim of this study is to develop a high performance semi-mechanism based approach to predict the conversion from MCI to AD and improve our understanding of MCI-to-AD conversion mechanism. First, analysis of variance (ANOVA) test and lasso regression are employed to identify the markers related to the conversion. Then the Bayesian network based on selected markers is established to predict MCI-to-AD conversion. The structure of Bayesian network suggests that the conversion may start with fibrin clot formation, verbal memory impairment, eating pattern changing and hyperinsulinemia. The Bayesian network achieves a high 10-fold cross-validated prediction performance with 96% accuracy, 95% sensitivity, 65% specificity, area under the receiver operating characteristic curve of 0.82 on data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The semi-mechanism based approach provides not only high prediction performance but also clues of mechanism for MCI-to-AD conversion. PMID- 27273262 TI - Canine models of allergic skin disease. PMID- 27273261 TI - Mutation design of a thermophilic Rubisco based on three-dimensional structure enhances its activity at ambient temperature. AB - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) plays a central role in carbon dioxide fixation on our planet. Rubisco from a hyperthermophilic archaeon Thermococcus kodakarensis (Tk-Rubisco) shows approximately twenty times the activity of spinach Rubisco at high temperature, but only one-eighth the activity at ambient temperature. We have tried to improve the activity of Tk-Rubisco at ambient temperature, and have successfully constructed several mutants which showed higher activities than the wild-type enzyme both in vitro and in vivo. Here, we designed new Tk-Rubisco mutants based on its three-dimensional structure and a sequence comparison of thermophilic and mesophilic plant Rubiscos. Four mutations were introduced to generate new mutants based on this strategy, and one of the four mutants, T289D, showed significantly improved activity compared to that of the wild-type enzyme. The crystal structure of the Tk-Rubisco T289D mutant suggested that the increase in activity was due to mechanisms distinct from those involved in the improvement in activity of Tk-Rubisco SP8, a mutant protein previously reported to show the highest activity at ambient temperature. Combining the mutations of T289D and SP8 successfully generated a mutant protein (SP8-T289D) with the highest activity to date both in vitro and in vivo. The improvement was particularly pronounced for the in vivo activity of SP8-T289D when introduced into the mesophilic, photosynthetic bacterium Rhodopseudomonas palustris, which resulted in a strain with nearly two-fold higher specific growth rates compared to that of a strain harboring the wild-type enzyme at ambient temperature. Proteins 2016; 84:1339-1346. (c) 2016 Wiley Periodicals, Inc. PMID- 27273263 TI - A series of lanthanide germanate cluster organic frameworks. AB - Six new lanthanide (Ln) germanate cluster organic frameworks (LnGeCOFs) derived from {Ln8Ge12} cage cluster units {[Nd(pza)2(H2O)] [Nd8Ge12(MU3 O)24E12(pza)(H2O)12]}.3H2O (1), {[Dy(CH3COO)(CO3)(H2O)]2[Dy8Ge12(MU3 O)24E12(H2O)12]}.11H2O (2), {[TbGeE(HO)2O(pza) (H2O)]2[Tb8Ge12(MU3 O)24E12(H2O)6]}.18H2O (3), {[DyGeE(HO)2O(C3H5NO2)(H2O)]2[Dy8Ge12(MU3 O)24E12(H2O)8]}.8H2O (4), {[Tb(pca)2 (H2O)]3[Tb8Ge12(MU3 O)24E12(H2O)4]}.(OH)3.10H2O (5) and {[Dy(pza)2(H2O)][Dy(pza)2(H2O)2][Dy(pza)3(H2O)][Dy8Ge12(MU3-O)24E12(pza)(HCOO) (H2O)6]}.5H2O (6) have been hydrothermally synthesized and structurally characterized. Increasing the amount of the second ligands can induce not only the assembly from 1 to 5, 6 based on Ln oxides as the starting sources, but also the assembly from 2 to 3, 4 based on Ln salts as the starting sources. The successful preparation of these LnGeCOFs suggests the importance of the second ligands in the structural construction of 1-6. To our knowledge, 1 is the first example that includes right- and left-handed helical chains among LnGeCOFs based on bis(carboxyethylgermanium)sesquioxide. 2, 4 and 6 are the first dysprosium incorporated organogermanates based on bis(carboxyethylgermanium)sesquioxide. 4 and 5 display very open framework structures with a solvent-accessible volume of 34.6% for 4 and 35.0% for 5. Moreover, the solid-state photoluminescence properties of 1, 3 and 5 have been investigated at room temperature and they exhibit the characteristic emission bands derived from Ln cations. PMID- 27273264 TI - Translation: Live stream: translation at single-mRNA resolution. PMID- 27273265 TI - Hepatoma-derived growth factor promotes growth and metastasis of hepatocellular carcinoma cells. AB - We aimed to elucidate the effects of hepatoma-derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real-time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP-2 and MMP-9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L < MHCC97H < HCCLM3). The growth and metastasis were suppressed by HDGF-siRNA. Gelatinolytic activities were enhanced in the three metastatic HCC cell lines, but had no significant difference among them. The tumourigenicity and metastatic capability of HCCLM3 cells in nude mice were inhibited after silencing HDGF. Meanwhile, HDGF-siRNA specifically suppressed the total and phosphorylated protein levels of ERK1/2, while not JNK, p38 and Akt. In conclusion, HDGF was overexpressed in HCC patients and cells, and HDGF might be closely correlated with HCC metastasis via regulating ERK signalling pathway. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273267 TI - Groundwater Down Under. PMID- 27273266 TI - Increased airway glucose increases airway bacterial load in hyperglycaemia. AB - Diabetes is associated with increased frequency of hospitalization due to bacterial lung infection. We hypothesize that increased airway glucose caused by hyperglycaemia leads to increased bacterial loads. In critical care patients, we observed that respiratory tract bacterial colonisation is significantly more likely when blood glucose is high. We engineered mutants in genes affecting glucose uptake and metabolism (oprB, gltK, gtrS and glk) in Pseudomonas aeruginosa, strain PAO1. These mutants displayed attenuated growth in minimal medium supplemented with glucose as the sole carbon source. The effect of glucose on growth in vivo was tested using streptozocin-induced, hyperglycaemic mice, which have significantly greater airway glucose. Bacterial burden in hyperglycaemic animals was greater than control animals when infected with wild type but not mutant PAO1. Metformin pre-treatment of hyperglycaemic animals reduced both airway glucose and bacterial load. These data support airway glucose as a critical determinant of increased bacterial load during diabetes. PMID- 27273268 TI - A highly specific and sensitive hepatitis C virus antigen enzyme immunoassay for One-step diagnosis of viremic hepatitis C virus infection. AB - The current standard in diagnosing hepatitis C virus (HCV) infection requires two sequential steps: anti-HCV test to screen, followed by HCV RNA reverse transcription polymerase chain reaction to confirm viremic HCV (V-HCV) infection. HCV core antigen tests provided potential for possible one-step diagnosis. However, low sensitivity and specificity limit their clinical utility. The present study developed a novel HCV antigens enzyme immunoassay (HCV-Ags EIA) and assessed its sensitivity, specificity, and utility for one-step diagnosis of V HCV infection using 365 serum specimens, including 176 without and 189 with V-HCV infection. First, we confirmed the presence of HCV nonstructural proteins 3, 4b, and 5a besides HCV core antigen during HCV infection and developed a novel HCV Ags EIA through simultaneous detection of all four HCV proteins. For the first time, the present study demonstrated that serum sample denaturation decreases the test specificity due to release of HCV-Ags sequestered in HCV immune complexes and should not be used in any HCV-Ags, including all the current HCV core antigen assays. On the other hand, using sample nondenaturation, the HCV-Ags EIA results showed 98.9% specificity and 100% sensitivity compared to serum anti-HCV and HCV RNA reverse-transcription polymerase chain reaction results. Using serum sample dilution, and nondenaturation, the lowest limits of detection of the HCV-Ags EIA were equivalent to serum HCV RNA levels of approximate 150-250 IU/mL. CONCLUSIONS: The highly specific and sensitive HCV-Ags EIA developed in the present study has the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL; using nondenaturation of serum samples, our HCV-Ags EIA reliably differentiated V-HCV infection from resolved HCV infection, accomplishing screening and diagnosis of V-HCV infection in one step. (Hepatology 2016;64:415-424). PMID- 27273269 TI - Longitudinal trajectories of intellectual and adaptive functioning in adolescents and adults with Williams syndrome. AB - BACKGROUND: Williams syndrome (WS) is associated with a distinct cognitive behavioural phenotype including mild to moderate intellectual disability, visual spatial deficits, hypersociability, inattention and anxiety. Researchers typically characterise samples of individuals with WS by their intellectual functioning and adaptive behaviour. Because of the low prevalence of the syndrome, researchers often include participants with WS across a broad age range throughout childhood and adulthood and assume participants demonstrate consistent cognitive development across ages. Indeed, IQ scores are generally stable for children and adolescents with WS, although there are significant individual differences. It is less clear whether this pattern of stable intellectual ability persists into adulthood. Furthermore, while adaptive behaviour is an important indicator of an individual's ability to apply their conceptual skills to everyday functioning, conflicting findings on the trajectories of adaptive behaviour in adolescents and adults with WS have been reported. The current study examined longitudinal profiles of cognitive and adaptive functioning in adolescents and adults with WS. METHOD: To examine cognitive functioning, participants included 52 individuals with WS (51.9% men) who were assessed with the Kaufman Brief Intelligence Test, 2nd edition (KBIT-2) between two and seven times. At their first assessment, participants had a mean age of 25.4 years (SD = 8.4), ranging in age from 14.2 to 48.9 years. To assess adaptive behaviour, participants included a subset of 28 individuals with WS whose parents completed the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II) between two and five times. At their initial administration, participants ranged from 17.1-40.2 years of age, with a mean age of 26.5 years (SD = 7.3). A series of multilevel models were used to examine changes in KBIT-2 Composite IQ, Verbal IQ and Nonverbal IQ standard scores over time, as well as the Adaptive Behavior Composite, and the Communication, Daily Living Skills and Socialization subdomains of the VABS-II. RESULTS: Consistent with the WS cognitive profile, IQ scores were significantly lower than the general population IQ score of 100, and there was significant variability in individual IQ scores and slopes. KBIT-2 IQ scores were generally stable across adolescents and adults with WS. Adaptive behaviour scores were significantly lower than the population mean score of 100, and there was significant variability in individuals' adaptive behaviour scores but not trajectories. However, in contrast to the findings with the KBIT-2, VABS-II scores were observed to significantly decrease over time. CONCLUSION: Findings suggest that while intellectual functioning remains stable, adaptive functioning does not remain stable across adolescence and adulthood in individuals with WS. Implications for the relation between cognitive and adaptive functioning across development are discussed, with a focus on how this relates to specific aspects of the WS phenotype. PMID- 27273270 TI - Effects of Orthokeratology on Choroidal Thickness and Axial Length. AB - PURPOSE: To investigate the effect of orthokeratology (ortho-k) treatment on choroidal thickness and its relationship with axial length change. METHODS: Seventy-seven myopic subjects aged between 7 and 17 years were treated with ortho k lenses (n = 39) or single-vision spectacle lenses (SVL, n = 38). Choroidal thickness and axial length measurements were taken at baseline and repeated 1 week and 3 weeks after lens wear for the ortho-k group and at 3 weeks for the SVL group. Parafoveal choroidal thickness was assessed using optical coherence tomography and segmented into nine regions according to the Early Treatment Diabetic Retinopathy Study (ETDRS) within a 6 * 6 mm circular zone centered on the fovea. Axial length was measured using partial coherence interferometry. The changes in subfoveal choroidal thickness were compared to the changes in axial length in both study groups. RESULTS: The change in axial length was significantly correlated with the change in choroidal thickness in both groups at 3 weeks (ortho-k, r = -0.351, p = 0.028 vs. SVL, r = -0.408, p = 0.011). Parafoveal choroidal thickness increased after 3 weeks of lens wear in the ortho k group (mean, 21.8 +/- 25.2 MUm) but did not change in the SVL group (mean, 0.1 +/- 19.7 MUm). Choroidal thickness significantly varied across the posterior retinal regions (F = 82.14, p < 0.001), with the temporal regions being thickest and nasal regions being thinnest. After 3 weeks of ortho-k treatment, the magnitude of change (range, 14.1-27.6 MUm) in choroidal thickness of the nine ETDRS regions was proportional to the baseline choroidal thickness in those regions (r = 0.88, p = 0.002). Axial length did not significantly change over time (F = 0.001, p = 0.975) and did not differ between the two treatment modalities (F = 0.305, p = 0.582). CONCLUSIONS: Choroidal thickness increases after short-term ortho-k treatment. Regional choroidal thickening after ortho-k treatment may be attributable to the altered retinal defocus profile associated with ortho-k lens wear. PMID- 27273271 TI - Retrograde Degeneration of Retinal Ganglion Cells Secondary to Head Trauma. AB - PURPOSE: To discuss the clinical case of a patient with transsynaptic retrograde degeneration (TRD) demonstrated by progressive retinal nerve fiber layer loss documented by serial spectral domain optical coherence tomography secondary to traumatic brain injury after 2 months post-trauma. CASE REPORT: A 25-year-old Caucasian male patient presented to a polytrauma rehabilitation center (PRC) for evaluation and treatment secondary to a severe traumatic brain injury (TBI) from a motorcycle accident 2 months before. Spectral-domain optical coherence tomography (SD-OCT) was completed at intervals that ranged between 8 and 42 days for a duration of 119 days. A comparison to the pre-trauma SD-OCT 10 months before revealed progressive thinning of the retinal nerve fiber layer (RNFL) in both eyes over multiple follow-ups post-trauma. Humphrey visual field (HVF) testing revealed an incomplete congruous right homonymous hemianopsia that gradually improved over the follow-ups. Analysis of the macular ganglion cell inner plexiform layer (GCIPL) thickness displayed loss that corresponded to the pattern of visual field defect. CONCLUSIONS: TRD can occur as soon as 2 months after severe TBI with damage posterior to the lateral geniculate nucleus. Progressive RNFL loss can be tracked with SD-OCT, and the rate of thinning may slowly stabilize over time. Visual field defects can improve months after the trauma but may not correspond to the progressive RNFL loss detected by SD-OCT. PMID- 27273272 TI - Eyelid Margin and Meibomian Gland Characteristics and Symptoms in Lens Wearers. AB - PURPOSE: To describe the lid margin characteristics of contact lens wearers and relate them to comfort during lens wear. METHODS: Three study sites enrolled habitual contact lens wearers. Subjects completed the Comfort domain of the Contact Lens User Experience (CLUE) questionnaire, and each eye was graded for the presence of mucocutaneous junction (MCJ) displacement, lid margin irregularity, and lid margin vascularity. Examiners counted the number of meibomian gland (MG) orifices in the central centimeter of the lower eyelid and the number of those that showed pouting/plugging and vascular invasion. MG expressibility was graded according to the Shimazaki schema. Subjects were grouped based on presence/absence of each characteristic, total number of orifices (>=5 vs. <5), and expressibility (grade 0 vs. >0). Descriptive statistics are reported. A linear model was used to assess the fixed effect of each characteristic on combined CLUE score and each CLUE statement, if the effect on combined CLUE score showed p < 0.10. RESULTS: The study included 203 subjects (67.5% female) with mean age (+/-SD) of 30.3 +/- 9.6 years. The most commonly observed characteristics were orifice pouting/plugging, compromised MG expressibility, and lid margin vascularity (35.0, 30.3, and 20.4%, respectively). MCJ displacement and MG expressibility had an effect on the combined CLUE score such that individual CLUE statements were analyzed (p = 0.01 and p = 0.06, respectively). MCJ displacement had an effect on comfort upon insertion (p = 0.01), comfort after 5 minutes (p = 0.03), end-of-day comfort (p = 0.01), and ability to maintain ocular moisture (p = 0.030). MG expressibility had a significant effect on general comfort (p = 0.01), comfort throughout the day (p = 0.02), and the ability to maintain ocular moisture (p = 0.02). CONCLUSIONS: MCJ displacement and MG expressibility have an effect on contact lens comfort. PMID- 27273273 TI - [Correction: Important Aspects of Diagnosis and Minimally Invasive Treatment of Metastases in the Spine Through the Plasma Field Therapy (Cavity Coblation Method)]. PMID- 27273274 TI - [Pathological Fractures of the Humerus: Experience with 76 Cases in a Musculoskeletal Oncology Centre]. AB - BACKGROUND: Pathological fractures can be caused by numerous local and systemic processes. The humerus is one of the commonest sites of pathological, tumour associated fractures. PATIENTS AND METHODS: In a retrospective study, 76 cases of pathological fractures of the humerus were analysed; 57 (75 %) were caused by a malignant disease, 19 fractures were associated with benign musculoskeletal disorders (25 %). The grade of the tumour, treatment strategy, intra- and postoperative complications, and survival rates in malignant tumours were documented. RESULTS: Two thirds of fractures were localised in the proximal third of the humerus. In 59 % of patients, malignant lesions were metastases (mainly renal cell, breast, lung and prostate cancer), followed by haemato-oncological diseases and primary sarcomas. Most benign tumours were simple bone cysts and enchondromas. A total of 70 patients were treated surgically and only 6 conservatively. Most malignant tumours were treated with compound osteosynthesis and tumour prostheses. Complications in both groups were rare. CONCLUSION: The demographic transition - with an increasing number of malignancies on the one hand and improved life expectancy under modern, adjuvant therapies on the other - will become a challenge in the treatment of pathological fractures of the humerus for a variety of disciplines. PMID- 27273286 TI - High-dose phenobarbital with intermittent short-acting barbiturates for acute encephalitis with refractory, repetitive partial seizures. AB - Acute encephalitis with refractory, repetitive partial seizures (AERRPS) is characterized by repetitive seizures during the acute and chronic phases and has a poor neurological outcome. Burst-suppression coma via continuous i.v. infusion of a short-acting barbiturate is used to terminate refractory seizures, but the severe side-effects of short-acting barbiturates are problematic. We report on a 9-year-old boy with AERRPS who was effectively treated with very-high-dose phenobarbital (VHDPB) combined with intermittent short-acting barbiturates. VHDPB side-effects were mild, especially compared with those associated with continuous i.v. infusion of short-acting barbiturates (dosage, 40-75 mg/kg/day; maximum blood level, 290 MUg/mL). Using VHDPB as the main treatment, short-acting barbiturates were used intermittently and in small amounts. This is the first report to show that VHDPB, combined with intermittent short-acting barbiturates, can effectively treat AERRPS. After treatment, convulsions were suppressed and daily life continued, but intellectual impairment and high-level dysfunction remained. PMID- 27273287 TI - Computational methods for identifying miRNA sponge interactions. AB - Recent findings show that coding genes are not the only targets that miRNAs interact with. In fact, there is a pool of different RNAs competing with each other to attract miRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The ceRNAs indirectly regulate each other via the titration mechanism, i.e. the increasing concentration of a ceRNA will decrease the number of miRNAs that are available for interacting with other targets. The cross-talks between ceRNAs, i.e. their interactions mediated by miRNAs, have been identified as the drivers in many disease conditions, including cancers. In recent years, some computational methods have emerged for identifying ceRNA-ceRNA interactions. However, there remain great challenges and opportunities for developing computational methods to provide new insights into ceRNA regulatory mechanisms.In this paper, we review the publically available databases of ceRNA-ceRNA interactions and the computational methods for identifying ceRNA-ceRNA interactions (also known as miRNA sponge interactions). We also conduct a comparison study of the methods with a breast cancer dataset. Our aim is to provide a current snapshot of the advances of the computational methods in identifying miRNA sponge interactions and to discuss the remaining challenges. PMID- 27273289 TI - A review of ensemble methods for de novo motif discovery in ChIP-Seq data. PMID- 27273290 TI - Structural database resources for biological macromolecules. AB - This Briefing reviews the widely used, currently active, up-to-date databases derived from the worldwide Protein Data Bank (PDB) to facilitate browsing, finding and exploring its entries. These databases contain visualization and analysis tools tailored to specific kinds of molecules and interactions, often including also complex metrics precomputed by experts or external programs, and connections to sequence and functional annotation databases. Importantly, updates of most of these databases involves steps of curation and error checks based on specific expertise about the subject molecules or interactions, and removal of sequence redundancy, both leading to better data sets for mining studies compared with the full list of raw PDB entries. The article presents the databases in groups such as those aimed to facilitate browsing through PDB entries, their molecules and their general information, those built to link protein structure with sequence and dynamics, those specific for transmembrane proteins, nucleic acids, interactions of biomacromolecules with each other and with small molecules or metal ions, and those concerning specific structural features or specific protein families. A few webservers directly connected to active databases, and a few databases that have been discontinued but would be important to have back, are also briefly commented on. Along the Briefing, sample cases where these databases have been used to aid structural studies or advance our knowledge about biological macromolecules are referenced. A few specific examples are also given where using these databases is easier and more informative than using raw PDB data. PMID- 27273288 TI - The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions. AB - Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. PMID- 27273291 TI - Conservative interdisciplinary treatment of a case with multiple facial and condyle fractures. AB - The purpose of this case report is to describe an interdisciplinary approach for a 51-year-old male who underwent multiple facial fractures including bilateral condyle fractures. The patient underwent emergency surgery, which included open reduction of the maxilla and mandibular symphysis and closed reduction of the bilateral condyle fractures. Although the patient recovered a comfortable range of mouth opening and alleviation of the temporomandibular joint (TMJ) symptoms after surgery, he suffered from a large anterior-posterior discrepancy due to less stability on the condyle-fossa relationships and from open bite with contacts only on both second molars and right second premolars. In this case, first, to increase the occlusal contact, comprehensive orthodontic treatment was completed. Second, occlusal equilibration was selectively performed to relieve the interferences and establish a stable range of mandibular movement without any changes in the vertical dimension. Third, both the upper central incisors and left lateral incisor were minimally restored with splinted and single zirconia crowns, which had modified lingual contours to provide adequate anterior guidance permitting the anterior-posterior discrepancy of the posterior teeth during protrusion. This conservative interdisciplinary treatment, including open and closed reduction, orthodontic treatment, occlusal adjustment, and minimal prosthetic restorations, resulted in a stable mandibular position and recovery of mastication function. PMID- 27273293 TI - ATLAAS: an automatic decision tree-based learning algorithm for advanced image segmentation in positron emission tomography. AB - Accurate and reliable tumour delineation on positron emission tomography (PET) is crucial for radiotherapy treatment planning. PET automatic segmentation (PET-AS) eliminates intra- and interobserver variability, but there is currently no consensus on the optimal method to use, as different algorithms appear to perform better for different types of tumours. This work aimed to develop a predictive segmentation model, trained to automatically select and apply the best PET-AS method, according to the tumour characteristics. ATLAAS, the automatic decision tree-based learning algorithm for advanced segmentation is based on supervised machine learning using decision trees. The model includes nine PET-AS methods and was trained on a 100 PET scans with known true contour. A decision tree was built for each PET-AS algorithm to predict its accuracy, quantified using the Dice similarity coefficient (DSC), according to the tumour volume, tumour peak to background SUV ratio and a regional texture metric. The performance of ATLAAS was evaluated for 85 PET scans obtained from fillable and printed subresolution sandwich phantoms. ATLAAS showed excellent accuracy across a wide range of phantom data and predicted the best or near-best segmentation algorithm in 93% of cases. ATLAAS outperformed all single PET-AS methods on fillable phantom data with a DSC of 0.881, while the DSC for H&N phantom data was 0.819. DSCs higher than 0.650 were achieved in all cases. ATLAAS is an advanced automatic image segmentation algorithm based on decision tree predictive modelling, which can be trained on images with known true contour, to predict the best PET-AS method when the true contour is unknown. ATLAAS provides robust and accurate image segmentation with potential applications to radiation oncology. PMID- 27273292 TI - Role of Cystathionine Gamma-Lyase in Immediate Renal Impairment and Inflammatory Response in Acute Ischemic Kidney Injury. AB - Hydrogen sulfide (H2S) is known to act protectively during renal ischemia/reperfusion injury (IRI). However, the role of the endogenous H2S in acute kidney injury (AKI) is largely unclear. Here, we analyzed the role of cystathionine gamma-lyase (CTH) in acute renal IRI using CTH-deficient (Cth(-/-)) mice whose renal H2S levels were approximately 50% of control (wild-type) mice. Although levels of serum creatinine and renal expression of AKI marker proteins were equivalent between Cth(-/-) and control mice, histological analysis revealed that IRI caused less renal tubular damage in Cth(-/-) mice. Flow cytometric analysis revealed that renal population of infiltrated granulocytes/macrophages was equivalent in these mice. However, renal expression levels of certain inflammatory cytokines/adhesion molecules believed to play a role in IRI were found to be lower after IRI only in Cth(-/-) mice. Our results indicate that the systemic CTH loss does not deteriorate but rather ameliorates the immediate AKI outcome probably due to reduced inflammatory responses in the kidney. The renal expression of CTH and other H2S-producing enzymes was markedly suppressed after IRI, which could be an integrated adaptive response for renal cell protection. PMID- 27273294 TI - Discrimination of Breast Cancer with Microcalcifications on Mammography by Deep Learning. AB - Microcalcification is an effective indicator of early breast cancer. To improve the diagnostic accuracy of microcalcifications, this study evaluates the performance of deep learning-based models on large datasets for its discrimination. A semi-automated segmentation method was used to characterize all microcalcifications. A discrimination classifier model was constructed to assess the accuracies of microcalcifications and breast masses, either in isolation or combination, for classifying breast lesions. Performances were compared to benchmark models. Our deep learning model achieved a discriminative accuracy of 87.3% if microcalcifications were characterized alone, compared to 85.8% with a support vector machine. The accuracies were 61.3% for both methods with masses alone and improved to 89.7% and 85.8% after the combined analysis with microcalcifications. Image segmentation with our deep learning model yielded 15, 26 and 41 features for the three scenarios, respectively. Overall, deep learning based on large datasets was superior to standard methods for the discrimination of microcalcifications. Accuracy was increased by adopting a combinatorial approach to detect microcalcifications and masses simultaneously. This may have clinical value for early detection and treatment of breast cancer. PMID- 27273295 TI - Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance. AB - Alternate-day fasting (ADF) causes body weight (BW) loss in humans and rodents. However, it is not clear that ADF while maintaining a high-fat (HF) diet results in weight loss and the accompanying improvement in control of circulating glucose. We tested the hypotheses that a high-fat ADF protocol in obese mice would result in (i) BW loss, (ii) improved glucose control, (iii) fluctuating phenotypes on 'fasted' days when compared to 'fed' days and (iv) induction of torpor on 'fasted days'. We evaluated the physiological effects of ADF in diet induced obese mice for BW, heart rate (HR), body temperature (Tb ), glucose tolerance, insulin responsiveness, blood parameters (leptin, insulin, free fatty acids) and hepatic gene expression. Diet-induced obese male C57BL/6J mice lost one-third of their pre-diet BW while on an ADF diet for 10 weeks consisting of HF food. The ADF protocol improved glucose tolerance and insulin sensitivity, although mice on a fast day were less glucose tolerant than the same mice on a fed day. ADF mice on a fast day had low circulating insulin, but had an enhanced response to an insulin-assisted glucose tolerance test, suggesting the impaired glucose tolerance may be a result of insufficient insulin production. On fed days, ADF mice were the warmest, had a high HR and displayed hepatic gene expression and circulating leptin that closely mimicked that of mice fed an ad lib HF diet. ADF mice never entered torpor as assessed by HR and Tb . However, on fast days, they were the coolest, had the slowest HR, and displayed hepatic gene expression and circulating leptin that closely mimicked that of Chow-Fed mice. Collectively, the ADF regimen with a HF diet in obese mice results in weight loss, improved blood glucose control, and daily fluctuations in selected physiological and biochemical parameters in the mouse. PMID- 27273297 TI - Isolation and Ambident Reactivity of a Chlorogermylenoid. AB - Treatment of 2,5-di(3,5-tert-butylphenyl)-1-lithioferrocene with GeCl2 ?dioxane afforded the corresponding chlorogermylenoid that exhibited an ambident reactivity in different solvents; it displayed a behavior characteristic for a dichlorogermylene anion in THF, while it exhibited the typical reactivity of a chlorogermylene in toluene. X-Ray diffraction analysis of a single crystal of this chlorogermylenoid, obtained from recrystallization in THF, revealed a separated-ion-pair structure in the solid state. PMID- 27273296 TI - Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy. AB - Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016. PMID- 27273298 TI - The effect of placing a bone replacement graft in the gap at immediately placed implants: a randomized clinical trial. AB - OBJECTIVE: To assess the added value of using a bone replacement graft in combination with immediate implants in reducing the bone dimensional changes occurring in the residual ridge. MATERIAL AND METHODS: Randomized parallel controlled clinical trial to study the efficacy of grafting with demineralized bovine bone mineral with 10% collagen (DBBM-C) in the gap between the implant surface and the inner bone walls when the implants were immediately placed in the anterior maxilla. The changes between implant placement and 16 weeks later in the horizontal and vertical crestal bone changes in relation to the implant were evaluated through direct bone measurements using a periodontal probe. Mean changes were compared between the experimental and control sites using parametric statistics. RESULTS: A total of 86 implant sites in 86 subjects were included in the analysis (43 in the test group and 43 in the control group). The horizontal crest dimension underwent marked changes during healing mainly at the buccal aspect of the alveolar crest where this reduction amounted to 1.1 (29%) in the test group and 1.6 mm (38%) in the control group, being these statistically significant (P = 0.02). This outcome was even more pronounced at sites in the anterior maxilla and with thinner buccal bone plates. CONCLUSIONS: In conclusion, the results from this clinical trial demonstrated that placing a DBBM-C bone replacement graft significantly reduced the horizontal bone resorptive changes occurring in the buccal bone after the immediate implantation in fresh extraction sockets. PMID- 27273299 TI - CD146 defines commitment of cultured annulus fibrosus cells to express a contractile phenotype. AB - Characterization of cells is important for facilitating cell-based therapies for degenerative diseases of intervertebral discs. For this purpose, we analyzed mouse annulus fibrosus cells by flowcytometory to detect phenotypic change in their primary cultures. After examination of sixteen cell surface proteins, we focused on CD146 that solely increased during culture expansion. CD146 is known to be a marker for mesenchymal stem cells and for their vascular smooth muscle commitment with expression of contractile phenotype enhanced by SM22alpha. We sorted CD146+ cells to elucidate their characteristics and the key factors that play a role in this change. Whole cell cultures showed the ability for tripotent differentiation toward mesenchymal lineages, whereas sorted CD146+ cells did not. Expression of CD146 was elevated by addition of transforming growth factor beta1, and sorted CD146+ cells expressed higher levels of mRNA for SM22alpha and Elastin than did CD146- cells. Morphologically, CD146+ cells more broadly deposited extracellular type I collagen than CD146- cells and showed filamentous actin bundles traversing their cytoplasm and cell-cell junctions. Moreover, CD146+ cells demonstrated significantly higher gel contraction properties than CD146- cells when they were embedded in collagen gels. Human annulus fibrosus CD146+ cells also showed higher contractility. Immunohistochemistry determined CD146+ cells localized to the outermost annulus layers of mouse intervertebral disc tissue with co-expression of SM22alpha. These results suggest that increment of CD146 expression indicates gradual change of cultured annulus fibrosus cells to express a contractile phenotype and that transforming growth factor beta1 enhances this cellular commitment. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1361-1372, 2016. PMID- 27273300 TI - Amphibian breeding phenology trends under climate change: predicting the past to forecast the future. AB - Global climate warming is predicted to hasten the onset of spring breeding by anuran amphibians in seasonal environments. Previous data had indicated that the breeding phenology of a population of Fowler's Toads (Anaxyrus fowleri) at their northern range limit had been progressively later in spring, contrary to generally observed trends in other species. Although these animals are known to respond to environmental temperature and the lunar cycle to commence breeding, the timing of breeding should also be influenced by the onset of overwintering animals' prior upward movement through the soil column from beneath the frost line as winter becomes spring. I used recorded weather data to identify four factors of temperature, rainfall and snowfall in late winter and early spring that correlated with the toads' eventual date of emergence aboveground. Estimated dates of spring emergence of the toads calculated using a predictive model based on these factors, as well as the illumination of the moon, were highly correlated with observed dates of emergence over 24 consecutive years. Using the model to estimate of past dates of spring breeding (i.e. retrodiction) indicated that even three decades of data were insufficient to discern any appreciable phenological trend in these toads. However, by employing weather data dating back to 1876, I detected a significant trend over 140 years towards earlier spring emergence by the toads by less than half a day/decade, while, over the same period of time, average annual air temperature and annual precipitation had both increased. Changes in the springtime breeding phenology for late-breeding species, such as Fowler's Toads, therefore may conform to expectations of earlier breeding under global warming. Improved understanding of the environmental cues that bring organisms out of winter dormancy will enable better interpretation of long-term phenological trends. PMID- 27273301 TI - Potential allergenicity response to structural modification of irradiated bovine alpha-lactalbumin. AB - Bovine alpha-lactalbumin (alpha-La) is a major food allergen found in milk and is characterized by high conformational stability because of its four disulfide bridges and being calcium bound. This study aimed to describe the influence of gamma irradiation on the structure and potential allergenicity of alpha-La. The prepared alpha-La was irradiated at doses of 1-10 kGy. The changes in structure were characterized through SDS-PAGE, circular dichroism spectroscopy, ultraviolet absorption spectroscopy, and fluorescence spectroscopy. The potential allergenicity of the irradiated alpha-La was evaluated in vitro through IgG/IgE inhibition ELISA and the human basophil KU812 degranulation assay. The results showed that the secondary and tertiary structures of alpha-La significantly changed and caused extensive protein denaturation and aggregation. IgG and IgE binding properties remarkably decreased, and the degranulation capacity of basophils weakened. The results suggested that structural damage of alpha-La induced by irradiation significantly reduces the potential allergenicity of alpha La. PMID- 27273302 TI - [Four years of specialized outpatient palliative care in a rural area : Cooperation and acceptability from general practitioners' view]. AB - BACKGROUND: In 2011, a specialized palliative home care was introduced in the counties of Landshut and Dingolfing. OBJECTIVES: The aim of the current survey was to evaluate the cooperation, acceptance and need of palliative measures for patients particulary from the general practitioner's perspective. METHODS: From January to March 2015, 198 general practitioners from the counties of Landshut and Dingolfing were contacted with questionnaires. The questionnaires consisted of 16 questions covering five different issues, and drew upon the practical experiences of the authors and earlier surveys from the literature. The questionnaires were sent by post containing a self-addressed and postpaid envelope. RESULTS: Completed questionnaires from 40 out of 198 contacted general practitioners (33 % female and 53 % male). Of these 85 % had cooperated with a SAPV team, 23 % had taken part in training for palliative medicine, 10 % intended to acquire a qualification and 10 % could imagine working in a SAPV team. In addition, 75 % stated that hospitalizations were avoided through the use of SAPV while 73 % felt that time and costs were saved for their own practices. The majority of general practitioners were satisfied with the work provided by the SAPV and the cooperation. Regarding additional palliative care for geriatric patients, 60 % believed that this was sensible. One main critique was that the information about including a patient in the SAPV program was transferred to the general practitioner too late. CONCLUSION: The current data show that general practitioners recognize the need for palliative medicine skills and predominately welcome the work of a specialized palliative care team in treating their patients. However, close cooperation and communication is necessary for a successful network between generalists and specialists in palliative care. PMID- 27273303 TI - [Celiac disease : Pathogenesis, clinics, epidemiology, diagnostics, therapy]. AB - Celiac disease is induced by the consumption of gluten containing cereals (wheat, spelt, barley, rye). With a prevalence of ~ 1 %, it is the most common non infectious chronic inflammatory intestinal disease worldwide. It manifests in all age groups, either classically with abdominal pain, diarrhoea and growth failure or weight loss, more commonly with indirect consequences of malabsorption, such as anaemia and osteoporosis, or with associated autoimmune diseases like type 1 diabetes, autoimmune thyroiditis or dermatitis herpetiformis. The pathogenesis of celiac disease is well explored. Gluten, the cereal storage protein, is not completely digested and reaches the intestinal mucosa where it activates inflammatory T cells, which cause atrophy of the resorptive villi. This T-cell activation requires a genetic predisposition (the molecules HLA-DQ2 or -DQ8 on antigen-presenting immune cells). Moreover, the enzyme tissue transglutaminase (TG2) which is released in the mucosa increases the immunogenicity of the gluten peptides by a deamidation reaction. The test for serum antibodies to the autoantigen TG2 is one of the best diagnostic markers in medicine, which in combination with endoscopically obtained biopsies, secures the diagnosis of celiac disease. Despite these tools celiac disease is severely underdiagnosed, with 80-90 % of those affected being undetected. The untreated condition can lead to grave complications. These include the consequences of malabsorption, cancers (especially intestinal T-cell lymphoma), and likely also the promotion of autoimmune diseases. The therapy of celiac disease, a strict gluten-free diet, is difficult to maintain and not always effective. Alternative, supporting pharmacological therapies are urgently needed and are currently in development. PMID- 27273304 TI - GPRC5A suppresses protein synthesis at the endoplasmic reticulum to prevent radiation-induced lung tumorigenesis. AB - GPRC5A functions as a lung tumour suppressor to prevent spontaneous and environmentally induced lung carcinogenesis; however, the underlying mechanism remains unclear. Here we reveal that GPRC5A at the endoplasmic reticulum (ER) membrane suppresses synthesis of the secreted or membrane-bound proteins including a number of oncogenes, the most important one being Egfr. The ER located GPRC5A disturbs the assembly of the eIF4F-mediated translation initiation complex on the mRNA cap through directly binding to the eIF4F complex with its two middle extracellular loops. Particularly, suppression of EGFR by GPRC5A contributes significantly to preventing ionizing radiation (IR)-induced lung tumorigenesis. Thus, GPRC5A deletion enhances IR-promoted EGFR expression through an increased translation rate, thereby significantly increasing lung tumour incidence in Gprc5a(-/-) mice. Our findings indicate that under-expressed GPRC5A during lung tumorigenesis enhances any transcriptional stimulation through an active translational status, which can be used to control oncogene expression and potentially the resulting related disease. PMID- 27273306 TI - Impact of Telemedicine in the Screening for Congenital Heart Disease in a Center from Northeast Brazil. AB - OBJECTIVES: To describe the incidence of congenital heart disease before and after the establishment of a telemedicine screening program, in a reference center from Northeast Brazil. METHODS: This is a descriptive, retrospective and comparative study based on the institutional data from a reference center in perinatology for a period of 16 years. Institutional data were collected from a 16-year period (2001-15). Data were divided into two periods: prior to (2001-11) and after (2012-15) the establishment of a telemedicine screening program. RESULTS: After the implementation of the screening process, almost all kinds of heart disease showed a significant increase in their incidence (p < 0.05). With this, the incidence of major heart diseases approached those specified in developed regions. CONCLUSION: The implementation of a screening process model for congenital heart diseases can change the context of patients with congenital heart diseases in poor regions. PMID- 27273305 TI - Deep brain stimulation mechanisms: the control of network activity via neurochemistry modulation. AB - Deep brain stimulation (DBS) has revolutionized the clinical care of late-stage Parkinson's disease and shows promise for improving the treatment of intractable neuropsychiatric disorders. However, after over 25 years of clinical experience, numerous questions still remain on the neurophysiological basis for the therapeutic mechanisms of action. At their fundamental core, the general purpose of electrical stimulation therapies in the nervous system are to use the applied electric field to manipulate the opening and closing of voltage-gated sodium channels on neurons, generate stimulation induced action potentials, and subsequently, control the release of neurotransmitters in targeted pathways. Historically, DBS mechanisms research has focused on characterizing the effects of stimulation on neurons and the resulting impact on neuronal network activity. However, when electrodes are placed within the central nervous system, glia are also being directly (and indirectly) influenced by the stimulation. Mounting evidence shows that non-neuronal tissue can play an important role in modulating the neurochemistry changes induced by DBS. The goal of this review is to evaluate how DBS effects on both neuronal and non-neuronal tissue can potentially work together to suppress oscillatory activity (and/or information transfer) between brain regions. These resulting effects of ~ 100 Hz electrical stimulation help explain how DBS can disrupt pathological network activity in the brain and generate therapeutic effects in patients. Deep brain stimulation is an effective clinical technology, but detailed therapeutic mechanisms remain undefined. This review provides an overview of the leading hypotheses, which focus on stimulation induced disruption of network oscillations and integrates possible roles for non neuronal tissue in explaining the clinical response to therapeutic stimulation. This article is part of a special issue on Parkinson disease. PMID- 27273307 TI - Pathophysiology, treatment and prevention of ovarian hyperstimulation syndrome. AB - PURPOSE OF REVIEW: Severe ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that affects 1% of women that undergo treatment with assisted reproductive technology. The review aims to summarize recent evidence on pathophysiology, treatment, and prevention of OHSS. RECENT FINDINGS: The pathophysiology is still not completely understood; however, vascular endothelial growth factor is likely to be an important mediator. Human chorionic gonadotropin was previously thought to be necessary for OHSS to occur; however, recent case reports have proven otherwise. The contribution of an attenuated anti-Mullerian hormone signalling pathway and CD11c + HLA-DR + dendritic cells and associated interleukins has been explored recently as contributors to pathogenesis.Treatment is largely supportive and is based mainly on consensus statements rather than evidence. Therefore, it is important to prevent this condition by identifying women at risk, allowing the clinician to implement preventive strategies, including the use of GnRH antagonist cycles with agonist triggers. SUMMARY: More research is required to elucidate the pathophysiology behind the condition. Clinicians should employ strategies to prevent OHSS. PMID- 27273308 TI - Considerations for minimally invasive gynecologic surgery in obese patients. AB - PURPOSE OF REVIEW: The purpose is to review the key anatomical and physiological changes in obese patients and their effects on preoperative, intraoperative, and postoperative care and to highlight the best practices to safely extend minimally invasive approaches to obese patients and provide optimal surgical outcomes in this high-risk population. RECENT FINDINGS: Minimally invasive surgery is safe, feasible, and cost-effective for obese patients. Obesity is associated with anatomical and physiological changes in almost all organ systems, which necessitates a multimodal approach and an experienced, multidisciplinary team. Preoperative counseling, evaluation, and optimization of medical comorbidities are critical. The optimal minimally invasive approach is primarily determined by the patient's anatomy and pathology. Specific intraoperative techniques and modifications exist to maximize surgical exposure and panniculus management. Postoperatively, comprehensive medical management can help prevent common complications in obese patients, including hypoxemia, venous thromboembolism, acute kidney injury, hyperglycemia, and prolonged hospitalization. SUMMARY: Given significantly improved patient outcomes, minimally invasive approaches to gynecological surgery should be considered for all obese patients with particular attention given to specific perioperative considerations and appropriate referral to an experienced minimally invasive surgeon. PMID- 27273309 TI - When and how to excise vaginal mesh. AB - PURPOSE OF REVIEW: Since 2011, there has been increasing attention paid to the use of synthetic grafts (mesh) in pelvic reconstructive surgery. Although synthetic grafts are considered permanent implants to improve outcomes, the use of this material has created inadvertent complications such as erosion, chronic pain, and dyspareunia. Patient evaluation is complex and surgical techniques carry risks not yet completely understood. This review summarizes current opinions in synthetic graft excision for the treatment of mesh-related complications. RECENT FINDINGS: Recent studies reveal excisions are being increasingly performed and graft placement is decreasing. Patients of lower volume surgeons have a higher risk of complication and need for excisional procedures. Pain is becoming the most common indication for vaginal mesh excision and that pain is mostly elicited with palpation of the mesh arms. Explantation is technically challenging and carries significant risks. SUMMARY: Vaginal synthetic graft complications are increasingly being managed by surgical excision. Careful evaluation of patient symptoms and objective findings should help guide management. Surgeons considering operative management should counsel patients regarding the risks of excision including but not limited to hemorrhage, nerve damage, muscular injury, and recurrent symptoms. PMID- 27273310 TI - Techniques in minimally invasive surgery for advanced endometriosis. AB - PURPOSE OF REVIEW: Surgery can be an important treatment option for women with symptomatic endometriosis. This review summarizes the recommended preoperative work up and techniques in minimally invasive surgery for treatment of deeply infiltrating endometriosis (DIE) involving the obliterated posterior cul-de-sac, bowel, urinary tract, and extrapelvic locations. RECENT FINDINGS: Surgical management of DIE can pose a challenge to the gynecologic surgeon given that an extensive dissection is usually necessary. Given the high risk of recurrence, it is vital that an adequate excision is performed. With improved imaging modalities, preoperative counseling and surgical planning can be optimized. It is essential to execute meticulous surgical technique and include a multidisciplinary surgical team when indicated for optimal results. SUMMARY: Advanced laparoscopic skills are often necessary to completely excise DIE. A thorough preoperative work up is essential to provide correct patient counseling and incorporation of the preferred surgical team to decrease complications and optimize surgical outcomes. Surgical management of endometriosis is aimed at ameliorating symptoms and preventing recurrence. PMID- 27273313 TI - Delayed-onset thrombocytopenia in a pediatric burn patient. PMID- 27273314 TI - Facile synthesis of sewage sludge-derived in-situ multi-doped nanoporous carbon material for electrocatalytic oxygen reduction. AB - Developing efficient, low-cost, and stable carbon-based catalysts for oxygen reduction reaction (ORR) to replace the expensive platinum-based electrocatalysts remains a major challenge that hamper the practical application of fuel cells. Here, we report that N, Fe, and S co-doped nanoporous carbon material, derived via a facile one-step pyrolysis of sewage sludge, the major byproduct of wastewater treatment, can serve as an effective electrocatalyst for ORR. Except for the comparable catalytic activity with commercial 20% Pt/C via a nearly four electron transfer pathway in both alkaline and acid medium, the as-synthesized co doped electrocatalyst also exhibits excellent methanol crossover resistance and outstanding long-term operation stability. The organic compounds in sewage sludge act as the carbon source and the in-situ N and S dopant in the fabrication, while the inorganic compounds serve as the in-built template and the in-situ Fe dopant. Our protocol demonstrates a new approach in the economic and eco-friendly benign reuse of sewage sludge, and also provides a straightforward route for synthesizing excellent carbon-based electrocatalysts as promising candidates for ORR directly from a type of waste/pollution. PMID- 27273315 TI - Shape-controlled anisotropy of superparamagnetic micro-/nanohelices. AB - Micro-/nanopropellers can be actuated remotely by a rotating magnetic field and steered at high precision through various fluidic environments. Recent progress comprises microfabrication of superparamagnetic microhelices not possessing remanent magnetization, but rather magnetized by an applied magnetic field. In this article we present a numerical approach for computing, from first principles, the effective susceptibility of polarizable helical micro /nanopropellers. We show that nanopropeller geometry, in particular, filament cross-section elongation and orientation, play a central role in determining its magnetic anisotropy and polarizability. The numerical predictions are in qualitative agreement with the previously reported experiments, showing that tight polarizable helices are propulsive. The numerical results are also supported by the approximate slender-body theory. Finally, we propose a semi quantitative energy criterion to rank polarizable helices with different geometries of the filament by their propulsive capacity and also estimate their maximal propulsion speed. PMID- 27273317 TI - Educating medical students in oral health care: current curriculum and future needs of institutions in Malaysia and Australia. AB - Poor oral health has been associated with compromised general health and quality of life. To promote comprehensive patient management, the role of medical professionals in oral health maintenance is compelling, thus indicating the need for educational preparation in this area of practice. This study aimed to determine the extent of training in oral health in Malaysian and Australian medical schools. An audio-recorded semi-structured phone interview involving Academic Programme Directors in Malaysian (n = 9, response rate=81.8%) and Australian (n = 7, response rate = 35.0%) medical schools was conducted during the 2014/2015 and 2014 academic years, respectively. Qualitative data was analysed via thematic analysis, involving coding and grouping into emerging themes. Quantitative data were measured for frequencies. It was found that medical schools in Malaysia and Australia offered limited teaching of various oral health-related components that were mostly integrated throughout the curriculum, in the absence of structured learning objectives, teaching methodologies and assessment approaches. Barriers to providing oral health education included having insufficient expertise and overloaded curriculum. As medical educators demonstrated support for oral health education, collaboration amongst various stakeholders is integral to developing a well-structured curriculum and practice guidelines on oral health management involving medical professionals. PMID- 27273316 TI - The Arabidopsis acetylated histone-binding protein BRAT1 forms a complex with BRP1 and prevents transcriptional silencing. AB - Transposable elements and other repetitive DNA sequences are usually subject to DNA methylation and transcriptional silencing. However, anti-silencing mechanisms that promote transcription in these regions are not well understood. Here, we describe an anti-silencing factor, Bromodomain and ATPase domain-containing protein 1 (BRAT1), which we identified by a genetic screen in Arabidopsis thaliana. BRAT1 interacts with an ATPase domain-containing protein, BRP1 (BRAT1 Partner 1), and both prevent transcriptional silencing at methylated genomic regions. Although BRAT1 mediates DNA demethylation at a small set of loci targeted by the 5-methylcytosine DNA glycosylase ROS1, the involvement of BRAT1 in anti-silencing is largely independent of DNA demethylation. We also demonstrate that the bromodomain of BRAT1 binds to acetylated histone, which may facilitate the prevention of transcriptional silencing. Thus, BRAT1 represents a potential link between histone acetylation and transcriptional anti-silencing at methylated genomic regions, which may be conserved in eukaryotes. PMID- 27273318 TI - History of endonasal skull base surgery. AB - While the endonasal approach to the skull base continues to advance, this paper invokes its long history. The centuries of medieval neuroanatomy and early neurosurgery enabled the conception of the first transfacial approaches in the late 1800s; Henry Schloffer performed the first transsphenoidal surgery in 1907. Although the procedure was initially met with much interest, Harvey Cushing eventually led the field of neurosurgery to abandon the transsphenoidal approach in the 1920s. The following three generations of neurosurgeons contained several key figures including Norman Dott, Gerard Guiot, and Jules Hardy who were steadfast in preserving the technique as well as in addressing its shortcomings. The endoscopic approach developed simultaneously, and advances in magnifying and fiberoptics further resolved limitations previously inherent to the transsphenoidal approach. At last, in the 1960s, the transsphenoidal approach entered its renaissance. Today, the momentum of its development persists in the endoscopic endonasal approach, which has recently expanded the indications for transsphenoidal surgery across the skull base, far beyond its original jurisdiction of the sella. Continued progress must not take for granted the rich history of the transsphenoidal approach, which was developed over centuries by surgeons around the world. The authors present the evolution of modern endonasal surgery as a dynamic interplay between technology, medicine, and surgery over the past 100 years. Progress can be attributed to courageous surgeons who affirmed their contemporary practices despite gaps in technology or medicine, and to visionary individuals who produced and incorporated new elements into transsphenoidal surgery. And so while the new endoscopic technique brings forth new challenges, its development reaffirms the principles laid down by the pioneers of transsphenoidal surgery. PMID- 27273319 TI - DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose. AB - Diabetes mellitus, characterized by abnormally high blood glucose levels, gives rise to impaired bone remodeling. In response to high glucose (HG), the attenuated osteogenic differentiation capacity of human periodontal ligament stem cells (hPDLSCs) is associated with the loss of alveolar bone. Recently, DNA methylation was reported to affect osteogenic differentiation of stem cells in pathological states. However, the intrinsic mechanism linking DNA methylation to osteogenic differentiation ability in the presence of HG is still unclear. In this study, we found that diabetic rats with increased DNA methylation levels in periodontal ligaments exhibited reduced bone mass and density. In vitro application of 5-aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to decrease DNA methylation levels in hPDLSCs, rescued the osteogenic differentiation capacity of hPDLSCs under HG conditions. Moreover, we demonstrated that the canonical Wnt signaling pathway was activated during this process and, under HG circumstances, the 5-aza-dC-rescued osteogenic differentiation capacity was blocked by Dickkopf-1, an effective antagonist of the canonical Wnt signaling pathway. Taken together, these results demonstrate for the first time that suppression of DNA methylation is able to facilitate the osteogenic differentiation capacity of hPDLSCs exposed to HG, through activation of the canonical Wnt signaling pathway. PMID- 27273321 TI - Few genetic and environmental correlations between life history and stress resistance traits affect adaptation to fluctuating thermal regimes. AB - Laboratory selection in thermal regimes that differed in the amplitude and the predictability of daily fluctuations had a marked effect on stress resistance and life history traits in Drosophila simulans. The observed evolutionary changes are expected to be the result of both direct and correlated responses to selection. Thus, a given trait might not evolve independently from other traits because of genetic correlations among these traits. Moreover, different test environments can induce novel genetic correlations because of the activation of environmentally dependent genes. To test whether and how genetic correlations among stress resistance and life history traits constrain evolutionary adaptation, we used three populations of D. simulans selected for 20 generations in constant, predictable and unpredictable daily fluctuating thermal regimes and tested each of these selected populations in the same three thermal regimes. We explored the relationship between genetic correlations between traits and the evolutionary potential of D. simulans by comparing genetic correlation matrices in flies selected and tested in different thermal test regimes. We observed genetic correlations mainly between productivity, body size, starvation and desiccation tolerance, suggesting that adaptation to the three thermal regimes was affected by correlations between these traits. We also found that the correlations between some traits such as body size and productivity or starvation tolerance and productivity were determined by test regime rather than selection regime that is expected to limit genetic adaptation to thermal regimes in these traits. The results of this study suggest that several traits and several environments are needed to explore adaptive responses, as genetic and environmentally induced correlations between traits as results obtained in one environment cannot be used to predict the response of the same population in another environment. PMID- 27273320 TI - Changes in pediatric waist circumference percentiles despite reported pediatric weight stabilization in the United States. AB - BACKGROUND: Obesity is a global health concern but the United States has reported a leveling in obesity rates in the pediatric population. OBJECTIVE: To provide updated waist circumference (WC) percentile values, identify differences across time and discuss differences within the context of reported weight stabilization in a nationally representative sample of American children. METHODS: Percentiles for WC in self-identified African Americans (AA), European Americans (EA) and Mexican Americans (MA) were obtained from 2009-2014 National Health and Nutrition Examination Survey data (NHANES2014). Descriptive trends across time in 10th, 25th, 50th, 75th and 90th percentile WC distributions were identified by comparing NHANES2012 with previously reported NHANESIII (1988-1994). RESULTS: WC increased in a monotonic fashion in AA, EA and MA boys and girls. When compared with NHANESIII data, a clear left shift of percentile categories was observed such that values that used to be in the 90th percentile are now in the 85th percentile. Differences in WC were observed in EA and MA boys during a reported period of weight stabilization. CONCLUSION AND RELEVANCE: WC has changed in the US pediatric population across time, even during times of reported weight stabilization, particularly among children of diverse racial/ethnic backgrounds. PMID- 27273322 TI - Identifying environmental correlates of intraspecific genetic variation. AB - Genetic variation is critical to the persistence of populations and their capacity to adapt to environmental change. The distribution of genetic variation across a species' range can reveal critical information that is not necessarily represented in species occurrence or abundance patterns. We identified environmental factors associated with the amount of intraspecific, individual based genetic variation across the range of a widespread freshwater fish species, the Murray cod Maccullochella peelii. We used two different approaches to statistically quantify the relative importance of predictor variables, allowing for nonlinear relationships: a random forest model and a Bayesian approach. The latter also accounted for population history. Both approaches identified associations between homozygosity by locus and both disturbance to the natural flow regime and mean annual flow. Homozygosity by locus was negatively associated with disturbance to the natural flow regime, suggesting that river reaches with more disturbed flow regimes may support larger, more genetically diverse populations. Our findings are consistent with the hypothesis that artificially induced perennial flows in regulated channels may provide greater and more consistent habitat and reduce the frequency of population bottlenecks that can occur frequently under the highly variable and unpredictable natural flow regime of the system. Although extensive river regulation across eastern Australia has not had an overall positive effect on Murray cod numbers over the past century, regulation may not represent the primary threat to Murray cod survival. Instead, pressures other than flow regulation may be more critical to the persistence of Murray cod (for example, reduced frequency of large floods, overfishing and chemical pollution). PMID- 27273323 TI - A longitudinal genetic survey identifies temporal shifts in the population structure of Dutch house sparrows. AB - Dutch house sparrow (Passer domesticus) densities dropped by nearly 50% since the early 1980s, and similar collapses in population sizes have been reported across Europe. Whether, and to what extent, such relatively recent demographic changes are accompanied by concomitant shifts in the genetic population structure of this species needs further investigation. Therefore, we here explore temporal shifts in genetic diversity, genetic structure and effective sizes of seven Dutch house sparrow populations. To allow the most powerful statistical inference, historical populations were resampled at identical locations and each individual bird was genotyped using nine polymorphic microsatellites. Although the demographic history was not reflected by a reduction in genetic diversity, levels of genetic differentiation increased over time, and the original, panmictic population (inferred from the museum samples) diverged into two distinct genetic clusters. Reductions in census size were supported by a substantial reduction in effective population size, although to a smaller extent. As most studies of contemporary house sparrow populations have been unable to identify genetic signatures of recent population declines, results of this study underpin the importance of longitudinal genetic surveys to unravel cryptic genetic patterns. PMID- 27273324 TI - Life-history traits and effective population size in species with overlapping generations revisited: the importance of adult mortality. AB - The relationship between life-history traits and the key eco-evolutionary parameters effective population size (Ne) and Ne/N is revisited for iteroparous species with overlapping generations, with a focus on the annual rate of adult mortality (d). Analytical methods based on populations with arbitrarily long adult lifespans are used to evaluate the influence of d on Ne, Ne/N and the factors that determine these parameters: adult abundance (N), generation length (T), age at maturity (alpha), the ratio of variance to mean reproductive success in one season by individuals of the same age (phi) and lifetime variance in reproductive success of individuals in a cohort (Vk*). Although the resulting estimators of N, T and Vk* are upwardly biased for species with short adult lifespans, the estimate of Ne/N is largely unbiased because biases in T are compensated for by biases in Vk* and N. For the first time, the contrasting effects of T and Vk* on Ne and Ne/N are jointly considered with respect to d and phi. A simple function of d and alpha based on the assumption of constant vital rates is shown to be a robust predictor (R(2)=0.78) of Ne/N in an empirical data set of life tables for 63 animal and plant species with diverse life histories. Results presented here should provide important context for interpreting the surge of genetically based estimates of Ne that has been fueled by the genomics revolution. PMID- 27273326 TI - Response of Blue Rubber Bleb Nevus Syndrome to Sirolimus Treatment. AB - BACKGROUND: Blue rubber bleb nevus syndrome (BRBNS) is a rare multifocal venous malformation syndrome involving predominantly the skin and gastrointestinal tract. Traditional treatment modalities include corticosteroids, interferon alpha, sclerotherapy, and aggressive surgical resection. Sirolimus has been used in several single case reports. PROCEDURE: We performed a single-institution retrospective review of four children with BRBNS, who received sirolimus as part of their treatment regimens. A diagnosis of BRBNS was based on clinical, radiologic, and pathologic criteria. RESULTS: Median age was 6.5 years (range: 2 16 years). Pathologic evaluations revealed a combined malformation with venous and lymphatic components. The novel finding of a lymphatic component was confirmed with PROX-1 immunostaining. Patients received oral sirolimus with target drug levels between 10 and 13 ng/ml. Responses to treatment were defined as stabilization/decrease in size of lesions; resolution of transfusion requirements; reduction in pain, and improvement in quality of life (QOL). Median time to response was 1.5 months (SD +/- 0.96 month, range: 1-3 months). Median follow-up was 21 months (range: 18-26 months). Lesion size and characteristics improved in all patients. All patients reported decrease in pain and improvement in QOL. All three patients requiring transfusions became transfusion-independent. One patient had resolution of coagulopathy. Adverse effects of sirolimus consisted of mucositis in three patients and neutropenia in one patient. CONCLUSIONS: Sirolimus is safe and efficient for the treatment of BRBNS. Further prospective studies are needed to evaluate the long-term effectiveness of this drug. This is the first report that identifies a lymphatic component as part of BRBNS. PMID- 27273325 TI - Population genetics of the Asian tiger mosquito Aedes albopictus, an invasive vector of human diseases. AB - The Asian tiger mosquito Aedes albopictus is currently one of the most threatening invasive species in the world. Native to Southeast Asia, the species has spread throughout the world in the past 30 years and is now present in every continent but Antarctica. Because it was the main vector of recent Dengue and Chikungunya outbreaks, and because of its competency for numerous other viruses and pathogens such as the Zika virus, A. albopictus stands out as a model species for invasive diseases vector studies. A synthesis of the current knowledge about the genetic diversity of A. albopictus is needed, knowing the interplays between the vector, the pathogens, the environment and their epidemiological consequences. Such resources are also valuable for assessing the role of genetic diversity in the invasive success. We review here the large but sometimes dispersed literature about the population genetics of A. albopictus. We first debate about the experimental design of these studies and present an up-to-date assessment of the available molecular markers. We then summarize the main genetic characteristics of natural populations and synthesize the available data regarding the worldwide structuring of the vector. Finally, we pinpoint the gaps that remain to be addressed and suggest possible research directions. PMID- 27273327 TI - OCT angiography in choroidal neovascularization secondary to choroidal osteoma. PMID- 27273328 TI - Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents. AB - Ophthalmic herpes simplex viral keratitis is responsible for a range of ocular manifestations from superficial epithelial disease to stromal keratitis and endotheliitis. The Herpetic Eye Disease Study has guided the management of herpetic eye disease for almost twenty years, but newer medications such as valacyclovir are now available and are considered to have better bioavailability than acyclovir. In this review, we examine the existing evidence on the pathogenesis of different ophthalmic herpes simplex viral keratitis disease modalities and the role of oral and topically administered antiviral drugs in the treatment of herpes simplex viral keratitis. PMID- 27273329 TI - Activity and topographic changes in the somatosensory system in embouchure dystonia. AB - BACKGROUND: Embouchure dystonia is a highly disabling focal task-specific dystonia affecting professional brass players. OBJECTIVE: This study was designed to analyze activity changes along with topographic representations in primary and nonprimary centers for somatosensory processing in patients with embouchure dystonia. METHODS: We used event-related functional magnetic resonance imaging with automized tactile stimulation of dystonic (upper lip) and nondystonic (forehead and dorsal hand) body regions in 15 professional brass players with and without embouchure dystonia. Statistical analyses included whole-brain between group comparisons of stimulation-induced activation and region-of-interest-based single patient analyses of topographic activation characteristics. RESULTS: Affected musicians revealed increased stimulation-induced activity in contralateral primary and bilateral secondary somatosensory representations of dystonic and nondystonic body regions as well as in the cerebellum ipsilateral to the left dystonic upper lip. Changes of somatotopic organization with altered intracortical distances and between-group differences of the centers of representations were found in the right primary and the bilateral secondary somatosensory cortex and in the left cerebellum. Positional variability of dystonic and nondystonic body regions was reduced with an emphasis on face representations. CONCLUSIONS: The present findings are supportive of the concept of an abnormal processing of somatosensory information in embouchure dystonia affecting multiple domains. The underlying neurophysiological mechanisms (eg, changes in inhibition, maladaptive plasticity, changes in baseline activity) remain unclear. The involvement of nondystonic body areas can be viewed in the context of possible compensation or an endophenotypic predisposition. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27273331 TI - Syphilis Screening in the 21st Century: New Recommendations for an Old Disease. PMID- 27273330 TI - A High-Voltage and High-Capacity Li1+x Ni0.5 Mn1.5 O4 Cathode Material: From Synthesis to Full Lithium-Ion Cells. AB - We report Co-free, Li-rich Li1+x Ni0.5 Mn1.5 O4 (0=55 years of age) and living in Lvliang City for at least 2 months a year were included. MEASUREMENTS: The participants were assessed regarding demographic characteristics, height, weight, as well as having a physical examination and blood sampling for serum cholesterol, total homocysteine (tHcy), folate, and vitamin B12 levels. RESULTS: The median (25th-75th percentile) tHcy concentration was 21.5 (15.8-33.6) umol/L in men and 18.0 (13.4-24.8) umol/L in women. The overall prevalence of hyperhomocysteinemia (tHcy >=15 umol/L) was 72.6% (84.3% in men and 63.2% in women), inversely correlated with folate (r=-0.230, P=0.006) and vitamin B-12 (r=-0.540, P<0.001), and positively correlated with uric acid (r=0.054, P<0.001). Vitamin B-12 and folate deficiency, older age, and male gender were associated with elevated tHcy; with vitamin B-12 deficiency being the strongest. CONCLUSIONS: Plasma tHcy concentration and hyperhomocysteinemia were significantly higher in this population than in previously studied populations. Vitamin B-12 and folate supplementation, concomitant lifestyle changes such as smoking cessation, and lipid-lowering treatments may help to decrease plasma tHcy concentrations and reduce the CVD risk in this population. PMID- 27273349 TI - Dietary Influence on Calcitropic Hormones and Adiposity in Caucasian and African American Postmenopausal Women Assessed by Structural Equation Modeling (SEM). AB - OBJECTIVES: To examine differences in hydroxycholecalciferol (25(OH)D) and parathyroid hormone (PTH) concentrations between Caucasian and African American (AA) postmenopausal women, as well as the effects of dietary calcium, protein and vitamin D intakes on 25(OH)D, PTH, and body adiposity using structural equation modeling (SEM). DESIGN: Population-based prospective cohort study. SETTING: Academic research using the baseline data from two longitudinal studies. Participants Included n=113 Caucasian and n=40 African American, postmenopausal women who completed the baseline data collection and met inclusion criteria (dietary calcium intake <900 mg/day and being generally healthy) between 2006 and 2010. MAIN OUTCOME: Dietary intake of calcium and vitamin D, assessed by dietary records, were examined in relation to calcitropic hormones concentrations and adiposity markers. Independent t-tests, confirmatory factor analysis, SEM and multi-group analyses were conducted to examine the aforementioned relationships as well as group differences among hormones, dietary intake, anthropometrics, age and other factors. RESULTS: Dietary calcium and protein intakes were significantly lower in AA women. Years since menopause were significantly higher in AA compared to Caucasian women. PTH and 25(OH)D levels were significantly lower in AA compared to Caucasian women. Dietary calcium and protein intakes did not influence body adiposity in either group of women. Dietary vitamin D had minimal indirect (via 25(OH)D levels) influence on adiposity. CONCLUSION: The study confirmed the positive relationship of 25(OH)D with adiposity markers and both AA and Caucasian women. The study provides a unique example of the use of SEM in nutrition research within a clinical context. This model should be further tested in other populations. PMID- 27273351 TI - Person-centered Feeding Care: A Protocol to Re-introduce Oral Feeding for Nursing Home Patients with Tube Feeding. AB - BACKGROUND: Although the literature on nursing home (NH) patients with tube feeding (TF) has focused primarily on the continuation vs. discontinuation of TF, the reassessment of these patients for oral feeding has been understudied. Re assessing patients for oral feeding may be better received by families and NH staff than approaches focused on stopping TF, and may provide an opportunity to address TF in less cognitively impaired patients as well as those with end-stage conditions. However, the literature contains little guidance on a systematic interdisciplinary team approach to the oral feeding reassessment of patients with TF, who are admitted to NHs. METHODS: This project had two parts that were conducted in one 170-bed intermediate/skilled, Medicare-certified NH in Honolulu, Hawai'i. Part 1 consisted of a retrospective observational study of characteristics of TF patients versus non-tube fed patients at NH admission (2003 2006) and longitudinal follow-up (through death or 6/30/2011) with usual care of the TF patients for outcomes of: feeding and swallowing reassessment, goals of care reassessment, feeding status (TF and/or per oral (PO) feedings), and hospice status. Part 2 involved the development of an interdisciplinary TF reassessment protocol through working group discussions and a pilot test of the protocol on a new set of patients admitted with TF from 2011-2014. RESULTS: Part 1: Of 238 admitted patients, 13.4% (32/238) had TF. Prior stroke and lack of DNR status was associated with increased likelihood of TF. Of the 32 patients with TF at NH admission, 15 could communicate and interact (mild, moderate or no cognitive impairment with prior stroke or pneumonia); while 17 were nonverbal and/or bedbound patients (advanced cognitive impairment or terminal disease). In the more cognitively intact group, 9/15 (60%) were never reassessed for tolerance of oral diets and 10/15 (66.7%) remained with TF without any oral feeding until death. Of the end-stage group, 13/17 (76.5%) did not have goals of care reassessed and remained with TF without oral feeding until death. Part 2: The protocol pilot project included all TF patients admitted to the facility in 2011 2014 (N=33). Of those who were more cognitively intact (n=22), 21/22 (95.5%) had swallowing reassessed, 11/22 (50%) resumed oral feedings but 11 (50%) failed reassessment and continued exclusive TF. Of those with end-stage disease (n=11), 100% had goals of care reassessed and 9 (81.8%) families elected individualized oral feeding (with or without TF). CONCLUSION: Using findings from our retrospective study of usual care, our NH's interdisciplinary team developed and pilot-tested a protocol that successfully reintroduced oral feedings to tube-fed NH patients who previously would not have resumed oral feeding. PMID- 27273350 TI - Genetic Variants of the FADS Gene Cluster Are Associated with Erythrocyte Membrane LC PUFA Levels in Patients with Mild Cognitive Impairment. AB - BACKGROUND: Long-chain (> 20 C-atoms) polyunsaturated fatty acids (LC PUFAs) of both the omega-6 (n-6) and omega-3 (n-3) series are important for the functional integrity of brain and thereby cognition, memory and mood. Clinical studies observed associations between altered LC PUFA levels and neurodegenerative diseases such as Alzheimer's disease and its prodromal stage, mild cognitive impairment (MCI). METHODS: The present study examined the LC PUFA status of MCI patients with specific view on the relative LC n-3 PUFA levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocyte membranes (omega-3 index). 12 single nucleotide polymorphisms (SNPs) of the FADS1, FADS2, and FADS3 gene clusters were genotyped in 111 MCI patients and evaluated associations with PUFA levels in erythrocyte membranes (primary outcome). In addition, the associations between FADS SNPs and LC PUFA levels with serum lipid levels as well as depressive symptoms were examined (secondary outcomes). RESULTS: Minor allele carrier of rs174546, rs174548 (FADS1), rs3834458, rs1535, rs174574, rs174575, rs174576, and rs174578 (FADS2) showed significant higher n-6 and n-3 precursor PUFA levels (linoleic acid, and alpha linolenic acid, respectively) and lower arachidonic acid (AA) levels in erythrocyte membranes compared to the major allele carriers. Differences in EPA and DHA levels were not significant. Minor allele carriers of rs174574, rs174576 and rs174578 (FADS2) and rs174455 (FADS3) exhibited significant higher triglyceride levels, whereas minor allele carriers for rs174449 and rs174455 (FADS3) exhibited significant higher total- and LDL-cholesterol levels compared to the more common variant. The mean omega-3 index of the study cohort was 6.19 +/- 1.55 %. In more than 85 % of the patients, the omega-3 index was below 8 % and in 23 % below 5 %. Moreover, it was shown that a low DHA status and omega-3 index was associated with depressive symptoms (Beck's depression-inventory). DISCUSSION AND CONCLUSION: These findings indicate an association between several FADS genotypes for higher n-6 and n-3 precursor PUFA and lower AA levels in erythrocyte membranes in minor compared to major allele carriers. To what extent FADS genotypes and a lower conversion of LA and ALA to biologically important LC PUFAs such as AA, EPA and DHA contributes to cognitive decline should be investigated in further trials. Nevertheless, the omega-3 index in this cohort of MCI patients can be classified as insufficient. PMID- 27273352 TI - The Protective and Therapeutic Effect of Exclusive and Combined Treatment with Alpha-ketoglutarate Sodium Salt and Ipriflavone on Bone Loss in Orchidectomized Rats. AB - OBJECTIVE: This study investigated the effect of alpha-ketoglutarate sodium salt (AKG) and ipriflavone (IP) treatment on the mineralization of the tibia in male rats during the development and after the establishment of osteopenia. DESIGN: One hundred and twenty eight male rats were randomly selected and submitted to either sham-operation (SHO) or orchidectomy (ORX), after which each group were then randomly divided between the two experiments. In Experiment-1, treatment with AKG or/and IP started after a 7-day recovery period, whereas in Experiment 2, the experimental protocol proceeded after a 60-day period of osteopenia establishment. AKG was then administered as an experimental drinking, at a concentration of 1.0 mol/l. As a control, a placebo solution was administered. IP at 50 mg/kg b.w., and physiological saline - PhS (as a control for IP) were applied daily via gavage. MEASUREMENTS: After 60 days of experimental treatment, in both experiments, the rats were sacrificed, their body weight recorded, while blood serum (Osteocalcin, CTX) and isolated tibia (weight, length, pQCT, DXA, 3 point bending test) were stored for further analysis. RESULTS AND CONCLUSIONS: Our results show that during the development of osteopenia, AKG and IP when applied exclusively, counteracts osteopenia development, whereas their usage after the establishment of osteopenia, significantly limits the development of bone disorders. Furthermore, combined treatment of AKG and IP exceeded the effects of their sole usage. In addition, during the development of osteopenia, AKG and IP not only inhibited bone resorption, but markedly stimulated the formation of bone tissue. Finally, after the development of osteopenia, combined treatment with AKG and IP protected the bone tissue against orchidectomy-induced bone loss. PMID- 27273353 TI - Prevalence of Glucosamine and Omega-3 Fatty Acid Use and Characteristics of Users among Mid-Age Women: Analysis of a Nationally Representative Sample of 10,638 Women. AB - BACKGROUND: There has been a dramatic increase in the use of dietary supplements over the last few decades and both omega-3 fatty acids and glucosamine are two of the best-selling dietary supplements in many countries. An understanding of omega 3 fatty acids and glucosamine consumption is of significance to health care providers and for future health promotion activities. METHODS: This research involved analysis of data collected from a nationally-representative sample of Australian women as part of the Australian Longitudinal Study on Women's Health (ALSWH). Participants' use of omega-3 fatty acids (FA), glucosamine, their demographics, health status and health care utilisation were measured. Analysis included logistic regression modelling. RESULTS: Of the 10,638 women in the study, 26.8% reported use of omega-3 FA and 15.9% glucosamine. Women with osteoarthritis (OR=2.529; 95% CI: 2.190, 2.921), other arthritis (OR= 1.618; 95% CI: 1.375, 1.905), and joint pain (OR= 2.699; 95% CI: 2.305, 3.160) were more likely to use glucosamine (all p<0.001). In contrast, those with diabetes (OR= 0.471; 95% CI: 0.343, 0.646) or depression (OR= 0.764; 95% CI: 0.657, 0.887) were less likely to use glucosamine (both p<0.001). Women with osteoarthritis (OR=1.481; 95% CI: 1.297, 1.691) and joint pain (OR= 1.456; 95% CI: 1.306, 1.622) were more likely to use omega-3 FA (all p<0.001). CONCLUSIONS: Substantial prevalence rates for use of glucosamine and omega-3 FA amongst mid-aged women highlights the need for health practitioners and policymakers to be mindful of the possible significant role of such supplement use as part of patient health seeking behaviours. PMID- 27273354 TI - Editorial: Frailty and Polypharmacy. PMID- 27273356 TI - Clinical and Functional Characterization of Pre-frailty among Elderly Patients Consulting Primary Care Centres. AB - BACKGROUND: Characterization of the main features of pre-frailty may contribute to better understanding the mechanisms involved in the development of frailty. OBJECTIVE: To characterize the pre-frail population consulting in primary care centres in Mataro (Catalonia, Spain), to describe the Fried's frailty criteria for this population and to identify the main associated factors. DESIGN: Cross sectional study. SETTING: Three primary care centres in Catalonia. PARTICIPANTS: Pre-frail subjects recruited from among persons aged 70 years and older consulting primary care centres and screened for frailty according to Fried's criteria. MEASUREMENTS: Clinical, nutritional and functional data. RESULTS: Frailty prevalence of 31.0% and pre-frailty prevalence of 49.0% were observed. Comorbidity was not especially frequent among elderly individuals classified as pre-frail (except for diabetes with 35.8% prevalence). Functional status and nutritional status were both reasonably satisfactory in pre-frail subjects with mean Barthel score of 98 points and 91% classified as well nourished. Among pre frail subjects, 35% were obese (body mass index>30); 75% reported pain; 12% had an accidental fall in the previous three months; and the mean number of medications ingested was 6.2. Weakness was the most prevalent frailty criterion (70%), followed by slowness (30%). Weakness was associated with age in men and with pain in women. Poor physical activity was associated with pain. CONCLUSIONS: Pre-frailty is very common among elderly subjects consulting primary care centres. Weakness, slowness, diabetes, pain and polypharmacy should alert healthcare professionals to the onset of a frailty process. PMID- 27273357 TI - Parathormone Levels Are Independently Associated with the Presence of Left Ventricular Hypertrophy in Patients with Coronary Artery Disease. AB - BACKGROUND: Abnormalities of mineral metabolism and inflammation may affect the cardiovascular system. We have assessed the relationship of left ventricular hypertrophy (LVH) with inflammation and mineral metabolism. METHODS: LVH was measured in 146 outpatients with stable coronary artery disease (SCAD) using echocardiography. Calcidiol (a vitamin D metabolite), parathyroid hormone (PTH), fibroblast growth factor-23, high-sensitivity C-reactive protein, MCP-1 (monocyte chemoattractant protein-1), galectin-3, NGAL (neutrophil gelatinase-associated lipocalin), and sTWEAK (soluble TNF-related weak inducer of apoptosis) plasma levels were studied. RESULTS: LVH, defined as septal thickness >=11 mm, was present in 19.9% of cases. These patients were older [75.0 (61.0-81.0) vs 64.0 (51.0-76.0) years; p=0.002], had higher prevalence of left ventricular ejection fraction (LVEF)>40%, and had higher PTH [84.7 (59.6-104.7) vs 63.2 (49.2-85.2) pg/ml; p=0.007], galectin-3 [9.6 (8.0-11.1) vs 8.3 (6.9-9.9) ng/ml; p=0.037], and NGAL (208.5+/-87.6 vs 173.9+/-73.4 ng/ml; p=0.031) plasma levels than those without LVH. Glomerular filtration rate was lower in patients with LVH than in those without it (65.1+/-20.0 vs 74.7+/-19.9 mL/min/1.73 m2; p=0.021). There were no significant differences in hypertension (79.3 vs 68.4%; p=0.363) or sex between both groups. Variables showing differences based on univariate analysis and hypertension were entered into a logistic regression analysis. Only age [odds ratio (OR) =1.052 (1.011-1.096); p=0.013], PTH plasma levels [OR=1.017 (1.003 1.031); p=0.021], and LVEF>40% [OR=7.595 (1.463-39.429); p=0.016] were independent predictors of LVH. CONCLUSIONS: In patients with SCAD, elevated PTH levels are independently associated with the presence of LVH. Further studies are needed to elucidate the role of PTH in the development of myocardial hypertrophy. PMID- 27273355 TI - A Comprehensive Fracture Prevention Strategy in Older Adults: The European Union Geriatric Medicine Society (EUGMS) Statement. AB - Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest Group on Falls and Fracture Prevention of the European Union Geriatric Medicine Society (EUGMS), in collaboration with the International Association of Gerontology and Geriatrics for the European Region (IAGG-ER), the European Union of Medical Specialists (EUMS), the International Osteoporosis Foundation - European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people. PMID- 27273358 TI - Inappropriate Use of Proton Pump Inhibitors in Elderly Patients Discharged from Acute Care Hospitals. AB - BACKGROUND: Proton-pump inhibitors (PPI) are extensively prescribed in older patients. However, little information is available on factors associated to PPI prescribing patterns among older patients discharged from hospital. OBJECTIVE: To evaluate the appropriateness and clinical correlates of PPI prescription at discharge in a population of 1081 older patients discharged from acute care Italian hospitals. DESIGN: We used data from the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) study, a multicenter observational study. The appropriateness of PPI prescriptions was defined according to the Italian Medicines Agency (AIFA) rules. Correlates of overprescribing (i.e prescribing without recognized AIFA indications) and underprescribing (i.e. not prescribing despite the presence of recognized AIFA indications) were investigated by logistic regression analysis. RESULTS: Overprescribing was observed in 30% of patients receiving PPIs at discharge. Underprescribing was observed in 11% of patients not receiving PPIs at discharge. Overprescribing of PPIs at discharge was negatively associated with age (OR=0.88, 95%CI=0.85-0.91), depression (OR=0.58, 95%CI=0.35-0.96), use of aspirin (OR=0.03, 95%CI=0.02-0.06) and systemic corticosteroids (OR=0.02, 95%CI=0.01-0.04). The negative association with number of medications (OR=0.95, 95%CI=0.88-1.03) and overall comorbidities (OR=0.92, 95%CI=0.83-1.02) was nearly significant. Conversely, older age (OR=1.09, 95%CI=1.04-1.14), use of aspirin (OR=24.0, 95%CI=11.5-49.8) and systemic corticosteroids (OR=19.3, 95%CI=11.5-49.8) and overall comorbidities (OR=1.22, 95%CI=1.04-1.42) were independent correlates of underprescribing. CONCLUSION: Overprescribing of PPIs is more frequent in younger patients with lower burden of depression, whilst underprescribing is characterized by older age and greater burden of comorbidity and polypharmacy. Hospitalization should be considered as a clue to identify inappropriate use of PPIs and improve appropriateness of prescribing. PMID- 27273359 TI - Visual Field Dependence Is Associated with Reduced Postural Sway, Dizziness and Falls in Older People Attending a Falls Clinic. AB - Moving visual fields can have strong destabilising effects on balance, particularly when visually perceived motion does not correspond to postural movements. This study investigated relationships between visual field dependence (VFD), as assessed using the roll vection test, and reported dizziness, falls and sway under eyes open, eyes closed and optokinetic conditions. Ninety five falls clinic attendees undertook the roll vection test (i.e. attempted to align a rod to the vertical while exposed to a rotating visual field). Sway was assessed under different visual conditions by centre of pressure movement. Participants also completed questionnaires on space and motion discomfort, fear of falling, depression and anxiety. Thirty four (35.8%) participants exhibited VFD, i.e. had an error > 6.5o in the roll vection test. Compared to participants without VFD, participants with VFD demonstrated less movement of the centre of pressure across all visual conditions, were more likely to report space and motion discomfort and to have suffered more multiple falls in the past year. VFD was independent of fear of falling, anxiety and depression. VFD in a falls clinic population is associated with reduced sway possibly due to a stiffening strategy to maintain stance, dizziness symptoms and an increased risk of falls. PMID- 27273360 TI - Letter to the Editor: Response to Re: Comments Referring to the Article "Comprehensive Nutritional Status in Sarco-osteoporotic Older Fallers". PMID- 27273362 TI - Correction: Hybrid nanostructures of metal/two-dimensional nanomaterials for plasmon-enhanced applications. AB - Correction for 'Hybrid nanostructures of metal/two-dimensional nanomaterials for plasmon-enhanced applications' by Xuanhua Li et al., Chem. Soc. Rev., 2016, 45, 3145-3187. PMID- 27273361 TI - Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure. AB - Pharmacological blockade of the N- and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of alpha1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2(-/ ) mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2(-/ ) mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2(+/+) mice. Interestingly, diabetic heterozygous Cav2.2(+/-) mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2(+/+) mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by omega conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-beta (TGF-beta) in podocytes was abolished with omega conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes. PMID- 27273363 TI - Synthesis of a Pentacene-Type Silaborin via Double Dehydrogenative Cyclization of 1,4-Diboryl-2,5-disilylbenzene. AB - A new pentacene-type silaborin, in which three benzene rings are bridged by silicon and boron atoms, has been synthesized and characterized by using NMR spectroscopy and X-ray crystallographic analysis. The precursor, 1,4 bis(dimesitylboryl)-2,5-bis(phenylsilyl)benzene (4), was prepared by stepwise introduction of a silyl group and a boryl group to a benzene ring starting from 1,4-dibromobenzene. Double cyclization of 4 proceeds by a H-Mes exchange and a B H/C-H dehydrogenative condensation to afford pentacene-type silaborin 5. X-ray crystal structure analysis reveals that 5 adopts a bent structure rather than a planar one. UV/Vis spectra and DFT calculations for 5 reveal a lowering of the LUMO energy level compared with corresponding anthracene-type 3. PMID- 27273364 TI - Finely Tuned Thermo-Responsive Block Copolymer Micelles for Photothermal Effect Triggered Efficient Cellular Internalization. AB - Although biodegradable amphiphilic block copolymer micelles have been widely applied in the clinical applications as drug delivery nanocarriers, low efficiency cellular internalization frequently reduces therapeutic efficacy of the loaded drugs. Here, photothermal effect-promoted cellular internalization of finely tuned thermo-responsive amphiphilic biodegradable block copolymer nanocarriers via noninvasive stimuli of near-infrared (NIR) light irradiation is demonstrated. Amphiphilic block copolymers, poly(epsilon-caprolactone)-block poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (PCL-b-P(NIPAM-co-DMA)), are prepared with finely tuned compositions of P(NIPAM-co-DMA) for desirable lower critical solution temperature of the block copolymer micelles in aqueous solution. The block copolymers are then used to co-encapsulate doxorubicin and indocyanine green, which show high encapsulation efficiency and significant photothermal effect upon exposure to NIR light irradiation. The photothermal effect-induced collapse and hydrophilic-to-hydrophobic transition of P(NIPAM-co DMA) shells significantly enhance the interactions between drug-loaded micelles and cell membranes, which dramatically promote the cellular internalization of the micelles and therapeutic efficacy of loaded anticancer drugs. PMID- 27273366 TI - Salvianolic acid A improves intestinal motility in diabetic rats through antioxidant capacity and upregulation of nNOS. AB - OBJECTIVE: This study aimed to detect the effect of a new herbal extract salvianolic acid A (SalA) on gastrointestinal complications in diabetic rats. METHODS: Altogether 80 rats were divided randomly into five groups, including normal control (NC) group, high-fat (HF) diet group, diabetes mellitus (DM) control group, and DM treated with SalA (0.1 mg/kg and 0.3 mg/kg) groups, respectively. DM was induced by feeding the rats with HF diet and the administration of streptozotocin (30 mg/kg). Four weeks after the establishment of the DM model, the rats received SalA or double distilled water for 8 weeks. After the evaluation of intestinal motility, the animals were sacrificed and their intestines were isolated and collected. The levels of advanced glycation end-products (AGE) and malondialdehyde (MDA) were detected. Protein gene product 9.5 (PGP9.5) and neuronal nitric oxide synthase (nNOS) expressions in the intestine were also detected. RESULTS: Compared with the NC and HF rats, the DM control rats showed significantly increased blood glucose level and decreased weight. Compared with the DM control group, SalA did not influence their weight and blood glucose level, but significantly reduced the levels of AGE and MDA. Intestinal transit was promoted by SalA in diabetic rats, and the expressions of PGP9.5 and nNOS in the intestine were both upregulated. CONCLUSION: The effect of SalA on the intestinal motility of diabetic rats might be due to its antioxidant capacity and restoring nNOS expression. PMID- 27273365 TI - Cell Deformation by Single-beam Acoustic Trapping: A Promising Tool for Measurements of Cell Mechanics. AB - We demonstrate a noncontact single-beam acoustic trapping method for the quantification of the mechanical properties of a single suspended cell with label free. Experimentally results show that the single-beam acoustic trapping force results in morphological deformation of a trapped cell. While a cancer cell was trapped in an acoustic beam focus, the morphological changes of the immobilized cell were monitored using bright-field imaging. The cell deformability was then compared with that of a trapped polystyrene microbead as a function of the applied acoustic pressure for a better understanding of the relationship between the pressure and degree of cell deformation. Cell deformation was found to become more pronounced as higher pressure levels were applied. Furthermore, to determine if this acoustic trapping method can be exploited in quantifying the cell mechanics in a suspension and in a non-contact manner, the deformability levels of breast cancer cells with different degrees of invasiveness due to acoustic trapping were compared. It was found that highly-invasive breast cancer cells exhibited greater deformability than weakly-invasive breast cancer cells. These results clearly demonstrate that the single-beam acoustic trapping technique is a promising tool for non-contact quantitative assessments of the mechanical properties of single cells in suspensions with label-free. PMID- 27273367 TI - An Unroofing Method to Observe the Cytoskeleton Directly at Molecular Resolution Using Atomic Force Microscopy. AB - An improved unroofing method enabled the cantilever of an atomic force microscope (AFM) to reach directly into a cell to visualize the intracellular cytoskeletal actin filaments, microtubules, clathrin coats, and caveolae in phosphate-buffered saline (PBS) at a higher resolution than conventional electron microscopy. All of the actin filaments clearly exhibited a short periodicity of approximately 5-6 nm, which was derived from globular actins linked to each other to form filaments, as well as a long helical periodicity. The polarity of the actin filaments appeared to be determined by the shape of the periodic striations. Microtubules were identified based on their thickness. Clathrin coats and caveolae were observed on the cytoplasmic surface of cell membranes. The area containing clathrin molecules and their terminal domains was directly visualized. Characteristic ridge structures located at the surface of the caveolae were observed at high resolution, similar to those observed with electron microscopy (EM). Overall, unroofing allowed intracellular AFM imaging in a liquid environment with a level of quality equivalent or superior to that of EM. Thus, AFMs are anticipated to provide cutting-edge findings in cell biology and histology. PMID- 27273368 TI - Children referred for evaluation for ADHD: comorbidity profiles and characteristics associated with a positive diagnosis. AB - BACKGROUND: The symptoms of attention-deficit/hyperactivity disorder (ADHD) are non-specific, and a range of possible causes and comorbidities need to be considered in children referred for assessment. OBJECTIVE: To examine the factors associated with ADHD diagnosis following multidisciplinary assessment. METHODS: Children underwent multidisciplinary evaluation including parent and teacher questionnaires; semi-structured interview to screen for internalizing and externalizing diagnoses; paediatric, psychology and special education assessments; and case conference. Predictors of ADHD diagnosis were examined in univariable and multivariable logistic regression models. RESULTS: Data from 190 assessments (82% male, mean age 6.8 years) were included. ADHD was diagnosed in 132 (70%) cases, of which 77% had one or more comorbidities. In children not diagnosed with ADHD, 60% had one or more alternate diagnosis made. Teacher reported ADHD symptom severity and learning difficulties were the strongest predictors of ADHD diagnosis. The pattern of comorbid/alternative diagnoses was similar between those diagnosed with ADHD and those not diagnosed with ADHD. CONCLUSIONS: Direct report from teachers is the most critical element of the clinical dataset for the evaluation for ADHD. These findings emphasize the importance of cross-situational impairment to ADHD diagnosis. The frequency and similarity of diagnoses in both groups highlight the overlapping nature of childhood developmental disorders, and the importance of evaluating for comorbid disorders regardless of the primary diagnosis. PMID- 27273369 TI - Relative Contributions of UVB and UVA to the Photoconversion of (6-4) Photoproducts into their Dewar Valence Isomers. AB - Dewar valence isomers are photoisomerization products of pyrimidine (6-4) pyrimidone photoproducts, a major class of UV-induced DNA lesions, which exhibits a maximal absorption around 320 nm. However, Dewar isomers are not produced in significant amounts in cells exposed to biologically relevant doses of UVB. In contrast, they are readily produced when cells are exposed to a combination of UVA and UVB. The present computational work demonstrates that, on the basis of known absorption properties and formation quantum yields, the difference in Dewar formation between the two types of radiation can be explained by the role of normal bases. In the UVB range, at the low level of (6-4) photoproducts present in cells exposed to realistic doses, normal bases are present in overwhelming amounts and absorb the vast majority of the incident photons. In contrast, the absorption of DNA bases is much weaker in the UVA range while that of (6-4) photoproducts is still significant, making photoisomerization possible. This two photon process makes it difficult to define an action spectrum for the formation of Dewar isomers. PMID- 27273370 TI - Ultrafast Brain MRI: Clinical Deployment and Comparison to Conventional Brain MRI at 3T. AB - BACKGROUND AND PURPOSE: To compare an ultrafast brain magnetic resonance imaging (MRI) protocol to the conventional protocol in motion-prone inpatient clinical settings. METHODS: This retrospective study was HIPAA compliant and approved by the Institutional Review Board with waived inform consent. Fifty-nine inpatients (30 males, 29 females; mean age 55.1, range 23-93 years)who underwent 3-Tesla brain MRI using ultrafast and conventional protocols, both including five sequences, were included in the study. The total scan time for five ultrafast sequences was 4 minutes 59 seconds. The ideal conventional acquisition time was 10 minutes 32 seconds but the actual acquisition took 15-20 minutes. The average scan times for ultrafast localizers, T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), diffusion-weighted, T2*-weighted sequences were 14, 41, 62, 96, 80, 6 seconds, respectively. Two blinded neuroradiologists independently assessed three aspects: (1) image quality, (2) gray-white matter (GM-WM) differentiation, and (3) diagnostic concordance for the detection of six clinically relevant imaging findings. Wilcoxon signed-rank test was used to compare image quality and GM-WM scores. Interobserver reproducibility was calculated. RESULTS: The ultrafast T1-weighted sequence demonstrated significantly better image quality (P = .005) and GM-WM differentiation (P < .001) compared to the conventional sequence. There was high agreement (>85%) between both protocols for the detection of mass-like lesion, hemorrhage, diffusion restriction, WM FLAIR hyperintensities, subarachnoid FLAIR hyperintensities, and hydrocephalus. CONCLUSIONS: The ultrafast protocol achieved at least comparable image quality and high diagnostic concordance compared to the conventional protocol. This fast protocol can be a viable option to replace the conventional protocol in motion-prone inpatient clinical settings. PMID- 27273372 TI - Response. PMID- 27273371 TI - Physico-Chemical Condition Optimization during Biosynthesis lead to development of Improved and Catalytically Efficient Gold Nano Particles. AB - Biosynthesis of nanoparticles has gained great attention in making the process cost-effective and eco-friendly, but there are limited reports which describe the interdependency of physical parameters for tailoring the dimension and geometry of nanoparticles during biological synthesis. In the present study, gold nanoparticles (GNPs) of various shapes and sizes were obtained by modulating different physical parameters using Trichoderma viride filtrate. The particles were characterized on the basis of visual observation, dynamic light scattering, UV-visible spectroscopy, transmission electron microscopy, fourier transform infrared spectroscopy, and X ray diffraction. While the size varied from 2-500 nm, the shapes obtained were nanospheres, nanotriangles, nanopentagons, nanohexagons, and nanosheets. Changing the parameters such as pH, temperature, time, substrate, and culture filtrate concentration influenced the size and geometry of nanoparticles. Catalytic activity of the biosynthesized GNP was evaluated by UV-visible spectroscopy and confirmed by gas chromatography-mass spectrometric analysis for the conversion of 4-nitrophenol into 4-aminophenol which was strongly influenced by their structure and dimension. Common practices for biodegradation are traditional, expensive, require large amount of raw material, and time taking. Controlling shapes and sizes of nanoparticles could revolutionize the process of biodegradation that can remove all the hurdles in current scenario. PMID- 27273374 TI - Accumulation of 11C-methionine in the normal pituitary gland on 11C-methionine PET. AB - Background For pituitary tumors, positron emission tomography (PET) with 11C methonine (MET) has been reported as feasible to facilitate diagnosis. MET is well-known to accumulate in the normal pituitary glands, but almost no studies have examined the degree of MET accumulation in the normal pituitary gland. Purpose To investigate accumulation of MET in normal pituitary gland on PET/CT. Material and Methods Among patients who underwent PET/CT using MET over the past 7 years, 77 patients who fulfilled our criteria for normal pituitary glands were retrospectively selected. Maximum standardized uptake value (SUVmax) for the pituitary gland was measured. Results SUVmax of MET in the pituitary gland was in the range of 0.9-6.6 (mean +/- standard deviation = 2.60 +/- 1.04). A negative correlation between SUVmax and patient age (y = -0.032 * + 4.29, n = 77, r = 0.55) was found by linear regression analysis. SUVmax of the pituitary gland did not differ significantly between women and men. Conclusion MET shows strong accumulation in normal pituitary gland. PET/CT would thus be feasible to differentiate between normal and abnormal pituitary glands. PMID- 27273375 TI - Detection of pulmonary embolism using repeated MRI acquisitions without respiratory gating: a preliminary study. AB - Background Pulmonary embolism (PE) is a severe medical condition with non specific clinical findings. Computed tomography angiography (CTA) using iodinated contrast agents is the golden standard for diagnosis, but many patients have contraindications for CTA. Purpose To investigate the diagnostic accuracy of repeated acquisitions of magnetic resonance imaging (MRI), without respiratory gating or breath holding, in diagnosing PE using CTA as the reference standard. Material and Methods Thirty-three patients with clinically suspected PE underwent MRI within 48 h after diagnostic CTA. A control group of 37 healthy participants underwent MRI and was matched with an equal number of negative CTA exams. The MRI protocol was based on free-breathing steady-state free precession producing 4.5 mm slices in axial, sagittal, and coronal planes. Instead of respiratory or cardiac gating five repetitive slices were obtained in each anatomical position to compensate for movement and artifacts. Clinical assessment including d-dimer and Well's score was performed prior to imaging. One radiologist reviewed the CTA exams and two radiologists reviewed the MRI scans. Results All 70 MRI exams were of diagnostic quality and the total acquisition time for each MRI scan was 9 min 34 s. On CTA, 29 patients were diagnosed with PE and the MRI readers detected 26 and 27 of those, respectively. Specificity was 100% for both readers. Sensitivity was 90% and 93%, respectively. Inter-reader agreement using Cohen's kappa was 0.97. Conclusion Our unenhanced MRI protocol shows a high sensitivity and specificity for PE, but further studies are required before considering it as a safe diagnostic test. PMID- 27273373 TI - Dowser++, a new method of hydrating protein structures. AB - A new method of hydrating protein structures, which we call Dowser++, is presented. The method is based on a semi-empirical modification of a popular program for protein hydration Dowser, and the usage of protocols AutoDock Vina, and WaterDock. The positions of water molecules predicted by Dowser++ were compared with experimental data for a set of 14 high-resolution crystal structures of oligopeptide-binding protein (OppA) containing a large number of resolved internal water molecules, as well as for the D- and K-channels of cytochrome c oxidase, and the recent data on PSII. Comparison is also made with the predictions of the original Dowser, and its improved version, Dowser+, described in our previous publication. We also present a model for quantitative estimation of the quality of water molecules placement made by a program, which includes an assumption of possible false negative data from the crystallographic analysis. The comparison of predictions made by Dowser++, Dowser and Dowser+ demonstrates significant improvement of predictive power of the new method. Proteins 2016; 84:1347-1357. (c) 2016 Wiley Periodicals, Inc. PMID- 27273376 TI - Abnormalities in gray and white matter volumes associated with explicit memory dysfunction in patients with generalized anxiety disorder. AB - Background The neuroanatomical abnormalities associated with behavioral dysfunction on explicit memory in patients generalized anxiety disorder (GAD) have not yet been clearly identified. Purpose To investigate the regional gray matter (GM) and white matter (WM) volume alterations over the whole brain in patients with GAD, as well as the correlation between the brain structural abnormality and explicit memory dysfunction. Material and Methods Twenty patients with GAD and 20 healthy controls matched for age, sex, and education level underwent high-resolution T1-weighted magnetic resonance imaging (MRI). The participants performed the explicit memory tasks with the neutral and anxiety inducing words. Results Patients with GAD showed significantly reduced GM volumes in the midbrain (MB), thalamus, hippocampus (Hip), insula, and superior temporal gyrus (STG); and reduced WM volumes in the MB, anterior limb of the internal capsule (ALIC), dorsolateral prefrontal cortex (DLPFC), and precentral gyrus (PrG). It is important to note that the GM volume of the Hip and the WM volume of the DLPFC were positively correlated with the recognition accuracy (%) in the explicit memory tasks with neutral and anxiety-inducing words, respectively. On the other hand, the WM volume of the PrG was negatively correlated with the reaction time in the same memory tasks. Conclusion This study demonstrated the regional volume changes on whole-brain GM and WM and the correlation between the brain structural alteration and explicit memory dysfunction in GAD patients. These findings would be helpful to understand the association between the brain structure abnormality and the functional deficit in the explicit memory in GAD. PMID- 27273377 TI - Portable Sequentially Shifted Excitation Raman spectroscopy as an innovative tool for in situ chemical interrogation of painted surfaces. AB - We present the first validation and application of portable Sequentially Shifted Excitation (SSE) Raman spectroscopy for the survey of painted layers in art. The method enables the acquisition of shifted Raman spectra and the recovery of the spectral data through the application of a suitable reconstruction algorithm. The technique has a great potentiality in art where commonly a strong fluorescence obscures the Raman signal of the target, especially when conventional portable Raman spectrometers are used for in situ analyses. Firstly, the analytical capability of portable SSE Raman spectroscopy is critically discussed using reference materials and laboratory specimens, comparing its results with other conventional high performance laboratory instruments (benchtop FT-Raman and dispersive Raman spectrometers with an external fiber optic probe); secondly, it is applied directly in situ to study the complex polychromy of Italian prestigious terracotta sculptures of the 16(th) century. Portable SSE Raman spectroscopy represents a new investigation modality in art, expanding the portfolio of non-invasive, chemically specific analytical tools. PMID- 27273378 TI - Prostate cancer: Across the Finnish line. PMID- 27273379 TI - Prostate cancer: Urology journals recommend new prostate cancer grade groups. PMID- 27273380 TI - Bladder cancer: FOXP3Delta3 involved in chemotherapy resistance. PMID- 27273381 TI - Suppressive effect of microRNA-29b on hepatic stellate cell activation and its crosstalk with TGF-beta1/Smad3. AB - The microRNA (miR)-29 family is closely associated with fibrotic processes by virtue of its low expression in many tissues during organ fibrosis. The present study investigated whether miR-29b overexpression suppressed hepatic stellate cell (HSC) activation and its interactions with transforming growth factor (TGF) beta1/mothers against decapentaplegic homolog 3 (Smad3), a classical signal transduction pathway contributing to the activation of HSCs. The results showed that transfection of LX-2 (human HSC) cells with miR-29b mimic or pSUPER-Smad3 silencing (si)RNA resulted in significantly increased expression of miR-29b and decreased expression of Smad3. miR-29b overexpression inhibited proliferation of LX-2 cells 24 h after transfection. Both miR-29b overexpression and Smad3 silencing antagonized the effects of TGF-beta1 on the expression of alpha-smooth muscle actin (alpha-SMA) and collagen type I (col-1). Furthermore, infection with miR-29b mimics suppressed Smad3 and TGF-beta1 expression, suggesting that miR-29b inhibited LX-2 activation mediated by both Smad3 and TGF-beta1. Nevertheless, primary miR-29a/b1, miR-29b2/c and mature miR-29b were downregulated by TGF-beta1 and stimulated by Smad3 silencing, suggesting that TGF-beta1/Smad3 signalling pathway regulate not just mature miR-29b but also its transcription. In summary, our results show overwhelming evidence corroborating the suppressive effect of miR-29b on TGF-beta1-induced LX-2 cell activation. The results also revealed the existence of crosstalk between miR-29b and TGF-beta1/Smad3 during LX-2 activation, suggesting a feedback loop between miR-29b and TGF-beta1/Smad3 signalling that promotes liver fibrosis. Copyright (c) 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd. PMID- 27273383 TI - A systematic literature review of the effectiveness of occupational health and safety regulatory enforcement. AB - BACKGROUND: We aimed to determine the strength of evidence on the effectiveness of legislative and regulatory policy levers in creating incentives for organizations to improve occupational health and safety processes and outcomes. METHODS: A systematic review was undertaken to assess the strength of evidence on the effectiveness of specific policy levers using a "best-evidence" synthesis approach. RESULTS: A structured literature search identified 11,947 citations from 13 peer-reviewed literature databases. Forty-three studies were retained for synthesis. Strong evidence was identified for three out of nine clusters. CONCLUSIONS: There is strong evidence that several OHS policy levers are effective in terms of reducing injuries and/or increasing compliance with legislation. This study adds to the evidence on OHS regulatory effectiveness from an earlier review. In addition to new evidence supporting previous study findings, it included new categories of evidence-compliance as an outcome, nature of enforcement, awareness campaigns, and smoke-free workplace legislation. Am. J. Ind. Med. 59:919-933, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273382 TI - Cardiac arrest triggers hippocampal neuronal death through autophagic and apoptotic pathways. AB - The mechanism of neuronal death induced by ischemic injury remains unknown. We investigated whether autophagy and p53 signaling played a role in the apoptosis of hippocampal neurons following global cerebral ischemia-reperfusion (I/R) injury, in a rat model of 8-min asphyxial cardiac arrest (CA) and resuscitation. Increased autophagosome numbers, expression of lysosomal cathepsin B, cathepsin D, Beclin-1, and microtubule-associated protein light chain 3 (LC3) suggested autophagy in hippocampal cells. The expression of tumor suppressor protein 53 (p53) and its target genes: Bax, p53-upregulated modulator of apoptosis (PUMA), and damage-regulated autophagy modulator (DRAM) were upregulated following CA. The p53-specific inhibitor pifithrin-alpha (PFT-alpha) significantly reduced the expression of pro-apoptotic proteins (Bax and PUMA) and autophagic proteins (LC3 II and DRAM) that generally increase following CA. PFT-alpha also reduced hippocampal neuronal damage following CA. Similarly, 3-methyladenine (3-MA), which inhibits autophagy and bafilomycin A1 (BFA), which inhibits lysosomes, significantly inhibited hippocampal neuronal damage after CA. These results indicate that CA affects both autophagy and apoptosis, partially mediated by p53. Autophagy plays a significant role in hippocampal neuronal death induced by cerebral I/R following asphyxial-CA. PMID- 27273384 TI - Pain Paroxysms With Coronal Radiation: Case Series and Proposal of a New Variant of Epicrania Fugax. AB - OBJECTIVE: We aim to report 4 patients with brief pain paroxysms whose clinical features remind of typical epicrania fugax (EF), except for the direction along a transverse trajectory. BACKGROUND: EF has been defined as a brief paroxysmal head pain, with stabbing quality, describing a linear or zig-zag trajectory across the surface of one hemicranium. METHODS: We considered all patients attending the headache outpatient office at 3 tertiary hospitals from March 2008 to December 2015. We identified a total of 4 cases with dynamic pain paroxysms moving in coronal direction. RESULTS: The mean age at onset was 49 years (range 34-75). All the patients suffered a dynamic pain from parietal or temporal areas to the contralateral ones, crossing the midline in a linear or zig zag trajectory, the entire sequence lasting 2-3 seconds. No triggers were identified. One patient noticed mild interictal tenderness at the stemming point. The frequency of the attacks varied from 2 per week to 1 every 2 months. No underlying disorders were identified by physical and neurological exams and neuroimaging and laboratory tests. CONCLUSIONS: Our patients presented with a paroxysmal head pain that might correspond to a transverse variant of EF. These observations may not only expand the EF phenotype but also reinforce the distinction between EF and pericranial neuralgias. PMID- 27273385 TI - Continuing the conversation: 30 years of motivational interviewing dissemination. PMID- 27273386 TI - Commentary on Smith et al. (2016): Gabapentin-looks like a drug that can be misused..., probably is a drug that can be misused. PMID- 27273387 TI - Commentary on Betts et al. (2016): Polysubstance use and opioid substitution therapy among people who inject drugs. PMID- 27273388 TI - Corrigendum. PMID- 27273390 TI - Secondary Acquired Cholesteatoma: Presentation and Tympanoplasty Outcomes. AB - OBJECTIVE: Comparing the clinical features and surgical outcomes of patients undergoing tympanoplasty for secondary acquired cholesteatoma (SAC) versus non complicated tympanic membrane perforation (TMP). STUDY DESIGN: Retrospective patient review. SETTING: Tertiary-care, academic center. PATIENTS: All 41 patients with diagnosis of SAC confirmed at surgery between January 1, 2007 and June 30, 2014, and an age-matched cohort consisting of patients with TMP. INTERVENTION(S): Tympanoplasty using either medial or lateral graft techniques. MAIN OUTCOME MEASURE(S): Resolution of perforation, SAC, and symptoms. RESULTS: Comparison between the two cohorts failed to reveal significant differences in otologic symptomology, or presentation. There was no significant difference in the resolution of SAC (p = 0.7) between the medial and lateral tympanoplasty techniques. Both techniques also had similar rates of success in the TMP cohort. The medial graft technique was significantly (p = 0.008) more likely to result in a successfully repaired tympanic membrane in the TMP cohort compared with the SAC cohort. The Lateral graft technique demonstrated no significant difference in the likelihood of TMP and SAC resolution. CONCLUSION: The presentation of SAC is similar to that of TMP despite being a separate clinical entity. A clinician's ability to distinguish the two is important to mitigate the destructive potential of untreated SAC and correctly council patients on tympanoplasty success rates. This study was unable to demonstrate a significant difference in disease control between the medial and lateral tympanoplasty techniques, although potential advantages of each technique are discussed. PMID- 27273391 TI - Auditory Brainstem Implantation in Chinese Patients With Neurofibromatosis Type II: The Hong Kong Experience. AB - OBJECTIVE: To describe our experience and outcomes of auditory brainstem implantation (ABI) in Chinese patients with Neurofibromatosis Type II (NF2). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Patients with NF2 who received ABIs. RESULTS: Between 1997 and 2014, eight patients with NF2 received 9 ABIs after translabyrinthine removal of their vestibular schwannomas. One patient did not have auditory response using the ABI after activation. Environmental sounds could be differentiated by six (75%) patients after 6 months of ABI use (mean score 46% [range 28-60%]), and by five (63%) patients after 1 year (mean score 57% [range 36-76%]) and 2 years of ABI use (mean score 48% [range 24-76%]). Closed-set word identification was possible in four (50%) patients after 6 months (mean score 39% [range 12-72%]), 1 year (mean score 68% [range 48-92%]), and 2 years of ABI use (mean score 62% [range 28 100%]). No patient demonstrated open-set sentence recognition in quiet in the ABI only condition. However, the use of ABI together with lip-reading conferred an improvement over lip-reading alone in open-set sentence recognition scores in two (25%) patients after 6 months of ABI use (mean improvement 46%), and five (63%) patients after 1 year (mean improvement 25%) and 2 years of ABI use (mean improvement 28%). At 2 years postoperatively, three (38%) patients remained ABI users. CONCLUSION: This is the only published study to date examining ABI outcomes in Cantonese-speaking Chinese NF2 patients and the data seems to show poorer outcomes compared with English-speaking and other nontonal language speaking NF2 patients. Environmental sound awareness and lip-reading enhancement are the main benefits observed in our patients. More work is needed to improve auditory implant speech-processing strategies for tonal languages and these advancements may yield better speech perception outcomes in the future. PMID- 27273392 TI - Long-term Results of ABI in Children With Severe Inner Ear Malformations. AB - OBJECTIVE: To report the long-term outcomes of children who received auditory brainstem implant (ABI) because of severe inner ear malformations. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral otolaryngology clinic. SUBJECTS AND METHODS: Between July 2006 and October 2014, 60 children received ABI at Hacettepe University. Preoperative work up included otolaryngologic examination, audiological assessment, radiological evaluation together with assessment of language development and psychological status. The surgeries were performed via retrosigmoid approach with a pediatric neurosurgeon. Intraoperatively, electrical auditory brainstem response was utilized. Initial stimulation was done 4 to 5 weeks postoperatively. Outcomes were evaluated with Categories of Auditory Performance (CAP), speech intelligibility rate (SIR), functional auditory performance of cochlear implant (FAPCI) and Manchester Spoken Language Development Scale scores; receptive and expressive language ages were determined. RESULTS: Sixty children who received ABI were between ages of 12 and 64 months. Thirty-five patients with follow up period of at least 1 year, were reported in means of long-term audiological and language results. The most prevelant inner ear malformation was cochlear hypoplasia (n = 19). No major complication was encountered. Majority of the patients were in CAP 5 category, which implies that they can understand common phrases without lip reading. SIR was found out to be better with improving hearing thresholds. Children with ABI were performing worse than average cochlear implantation (CI) users when FAPCI scores were compared. Patients with the best hearing thresholds have expressive vocabulary of 50 to 200 words when evaluated with Manchester Spoken Language Development Scale. There was no relationship between the number of active electrodes and hearing thresholds. The type of inner ear anomaly with the best and the worst hearing thresholds were common cavity and cochlear aperture aplasia, respectively. Patients with additional handicaps had worse outcomes. Among 35 children, 29 had closed set discrimination and 12 developed open set discrimination above 50%. It was determined that, progress of the patients is faster in the initial 2 years when compared with further use of ABI. CONCLUSION: ABI is an acceptable and effective treatment modality for pediatric population with severe inner ear malformations. Bilateral stimulation together with CI and contralateral ABI should be utilized in suitable cases. PMID- 27273393 TI - The Impact of Smoking on Ossiculoplasty Outcomes. AB - OBJECTIVES: To assess the impact of tobacco smoking on outcomes after ossiculoplasty. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. PATIENTS: Adult patients (16-88 yr of age) undergoing ossiculoplasty with cartilage tympanoplasty. OUTCOME MEASURES: Patients were classified as smokers (TOB) or nonsmokers (TOB). Comparisons were then made between these two groups with regard to early and late audiometric outcomes, rate of cure of conductive hearing loss, rate of successful graft healing, and incidence of complications after surgery. RESULTS: There was no significant difference between the two groups with regard to postoperative DeltaPTA-ABG (change in pure-tone average air-bone gap) (-14.4 dB vs. -14.6 dB for TOB vs. TOB, respectively, p = 0.946) or final audiometric outcome (DeltaPTA-ABGfinal) (-13.6 dB vs. -11.7 dB for TOB vs. TOB, respectively, p = 0.315), cure of conductive hearing loss, defined as closure of the PTA-ABG to <=20 dB HL, at postoperative audiometry (75.0% [129/172] for the TOB group vs. 69.3% [52/75] for the TOB group, p = 0.355), late audiometry (71.4% [105/147] for the TOB group vs. 66.7% [44/66] for the TOB group, p = 0.483), or successful graft healing (99.4% in the TOB group vs. 98.7% in the TOB group, p = 0.544). However, complications were observed significantly (p = 0.0003) more often in the TOB group (34.7% [26/75]) than the TOB group (14.5% [25/172]). CONCLUSION: Smoking is not a significant risk factor for anatomic failure of cartilage tympanic membrane graft or worsened audiometric outcome after ossiculoplasty. However, complications were significantly more common in smokers, supporting the practice of primary tympanostomy tube placement at the time of ossiculoplasty. PMID- 27273394 TI - Flat-Panel CT Imaging for Individualized Pitch Mapping in Cochlear Implant Users. AB - OBJECTIVE: This study aims to identify electrode contact location and to assess frequency deviation between predicted and actual frequency allocation maps in cochlear implant (CI) users. STUDY DESIGN AND METHODS: This is a retrospective clinical study. Flat-panel computed tomography (FPCT) scans were collected for 17 CI users. Cochlear length was measured using three-dimensional curved multiplanar reconstruction on high-resolution secondary reconstructions. Each electrode's percentage of distance from the base of the helicotrema was measured, and a modified Greenwood's function was applied. The patients' frequency allocation maps were retrieved from electronic medical records and compared with their calculated characteristic frequencies. RESULTS: Our results revealed that reprogramming based on FPCT imaging findings might improve 83% (n = 216) of 260 electrode contacts. The most basal and apical electrodes (12, 11, 10, 5, 4, 3, 2, and 1) most consistently deviated (>83% of the time) from their theoretical characteristic frequencies; the basal electrodes undershot and the apical electrodes overshot their theoretical values. Frequency mismatch between the characteristic frequencies of auditory neurons and programmed center frequencies ranges from 0.41 to 1.51 in octave bands. CONCLUSIONS: Using FPCT imaging and a modified Greenwood's function, we identify a mathematical discrepancy between theoretical and actual CI placement with respect to frequency-place mapping. We demonstrate a clinically reproducible and direct assessment of frequency-place mismatch. Our individualized calculations account for inter-individual variability in cochlear lengths, operative differences in insertion depths, and electrode array kinking within the cochlea. The benefits of allocating electrode contact frequencies to their tonotopy-derived locations in the cochlea were not investigated in this study, and future prospective trials are needed to demonstrate the consequences of personalized pitch mapping for CI users with respect to speech and pitch perception. PMID- 27273395 TI - The Tightrope Facial Nerve-An Unsupported Mastoid Segment After Resection of Recidivistic Cholesteatoma. AB - OBJECTIVES/HYPOTHESIS: Cholesteatomas are epidermal inclusion cysts containing stratified squamous epithelium that arise in the middle ear and mastoid cavities resulting in a persistent inflammatory state. Complications include chronic otorrhea, granulation tissue, and bony erosion. Cholesteatoma growth patterns predict frequent involvement of the Fallopian canal of the facial nerve. Extensive disease may extend to the posterior and middle fossa dura, the otic capsule, the carotid artery, and the jugular bulb. Dehiscence of the Fallopian canal and direct involvement of the facial nerve epineurium by cholesteatoma are risk factors for intraoperative facial nerve injury during tympanomastoid surgery by exposing the facial nerve to mechanical trauma and inflammation during microdissection. We present two cases of recidivistic cholesteatoma with unusual medial involvement of the vertical segment of the facial nerve that resulted in an unsupported mastoid segment after resection. The outcomes from these two patients suggest that facial nerve function may be preserved despite circumferential exposure with appropriate preoperative planning and intra operative techniques. STUDY DESIGN: Case studies. METHODS: Two patients undergoing revision tympanomastoidectomy for extensive recidivistic cholesteatoma with medial involvement of the facial nerve in the mastoid segment. In each case, the facial nerve was circumferentially exposed during the resection of the cholesteatoma. RESULTS: Normal facial nerve function after surgery was confirmed in both patients at 18 months and 6 years, respectively. CONCLUSIONS: Surgical resection of extensive cholesteatoma with medial involvement of the vertical segment of the facial nerve resulted in an unsupported mastoid segment in two patients with normal postoperative facial nerve function. PMID- 27273396 TI - Magnetic Resonance Imaging Compatibility of a New Generation of Active Middle Ear Implant: A Clinically Relevant Temporal Bone Laboratory Study. AB - OBJECTIVE: Magnetic resonance imaging (MRI) has become an essential tool of modern medical imaging and disease diagnosis. In November 2014, a new MRI conditional (up to 1.5 T) generation of an active middle ear implant (AMEI) was released to the market.The aim of the study was to test the MRI compatibility of the new implant system in a clinical-anatomical study. DESIGN: Experimental cadaver head model. SETTING: Temporal bone laboratory. PARTICIPANTS: AMEIs were implanted in 28 fixed temporal bones at three different floating mass transducer (FMT)-coupling positions (N = 8 short process of the incus, N = 16 long process of the incus, N = 4 round window). MAIN OUTCOME MEASURES: The position of the FMT and the integrity of the ossicular chain was monitored through microscopy, microendoscopy, and computed tomography (CT) scans before and after the MRI (1.5 T) was conducted. Proper function of the implant was tested with reverse transfer function (RTF) measurements. RESULTS: Neither positional nor functional changes after MRI were observed. CONCLUSION: The new generation of the AMEI is a MRI compatible system, which features an easier and quicker implant fixation method. The option of MRI in patients with AMEI should be taken into consideration during the preoperative discussion with potential candidates. PMID- 27273397 TI - Relationship Between Clinical Test Results and Morphologic Severity Demonstrated by Sitting 3-D CT in Patients With Patulous Eustachian Tube. AB - OBJECTIVE: To investigate the correlation of sitting 3-D computed tomography (CT) scans of the Eustachian tube (ET) with subjective and objective findings in patients with patulous Eustachian tube (PET). STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. SUBJECTS: A retrospective survey of medical records in Sen-En Hospital identified 40 patients and 62 ears with PET between September 2014 and June 2015. METHOD: Diagnosis of PET was based on the presence of three characteristic aural symptoms (autophony of voice or breathing sounds, and aural fullness), as well as verification of synchronous movement of the tympanic membrane in response to forced breathing under an endoscope. Any pressure changes in the external auditory canal (EAC) elicited by deep breathing and sniffing were detected by tubotympanoaerodynamography (TTAG). In addition, sonotubometry was performed where two parameters were used determined to evaluate ET function. Patients were examined by 3-D CT (Accuitomo; Morita, Kyoto, Japan) in the sitting position. The length of the closed ET lumen section was measured. Ears were divided into three groups as follows: completely open, closed-short (3 mm or less), and closed-long (longer than 3 mm). RESULTS: The median length of the closed section of the ET lumen was 1.85 +/- 2.69 mm in positive findings of PET. The three groups were significantly different in both aural fullness (p = 0.023) and, similarly, the difference in tympanic membrane movement (p = 0.032) among these three groups was also significantly different (p = 0.032). However, for autophony of breathing sounds, there was no significant difference with regard to autophony of breathing sounds among these three groups (p = 0.324). Although TTAG findings were did not reveal any significantly difference among these three groups (p = 0.589), the difference was significant (p = 0.001) in degree of EAC pressure change in TTAG. The difference among the three groups was significant (p = 0.001) based on sonotubometry findings. CONCLUSION: Under resting conditions, the lengths of the closed area of the ETs in PET groups are clearly shorter than in groups without PET based on sitting position CT scans in resting condition. Among the symptoms and clinical test findings including the ET function test results, the presence of tympanic membrane movement induced by respiration, the high degree of EAC pressure change in TTAG, as well as the positive results of sonotubometry are significantly correlated with the positive findings of sitting CT revealing the open ET. PMID- 27273398 TI - Primary Epidermoid Tumors of the Cerebellopontine Angle: A Review of 47 Cases. AB - OBJECTIVE: To analyze disease presentation, treatment, and clinical course of a consecutive series of patients with primary cerebellopontine angle (CPA) epidermoids. PATIENTS: Forty-seven consecutive patients with previously untreated CPA epidermoids. INTERVENTION(S): Observation and microsurgery. MAIN OUTCOME MEASURES: Disease- and treatment-associated morbidity, recurrence. RESULTS: Forty seven patients (mean age 39 years; 53% women) were analyzed and the average duration of follow-up was 42 months. The most common presenting symptom was headache (27; 57%); 13 (28%) exhibited preoperative asymmetric sensorineural hearing loss, 3 (6%) facial nerve paresis, and 3 (6%) hemifacial spasm. Thirteen patients (28%) were initially observed over a mean interval of 56 months; however, five experienced disease progression requiring operation. Thirty-nine patients (83%) underwent surgical resection; 18 (46%) received gross total, 5 (13%) near total, and 16 (41%) aggressive subtotal resection. Three patients (8%) recurred at a median of 53 months; two after subtotal and one after gross total resection. Ninety-three percent of patients with useful hearing maintained serviceable hearing following treatment and one patient (3%) experienced mild long-term postoperative facial nerve paresis (HB II/VI). All patients with preoperative facial nerve paresis recovered normal function postoperatively. There were no episodes of stroke or death. CONCLUSIONS: Surgical intervention is effective in alleviating symptoms of cranial neuropathy and brainstem compression from CPA epidermoids. Gross total resection is preferred; however, aggressive subtotal removal should be considered with adherent or extensive disease as reoperation rates are low, even in the setting of aggressive subtotal resection. Conservative observation with serial imaging is a viable initial strategy in asymptomatic or minimally symptomatic patients. PMID- 27273399 TI - Asymmetrical Hearing Loss in Cases of Industrial Noise Exposure: A Systematic Review of the Literature. AB - OBJECTIVE: Asymmetrical hearing thresholds are common in people claiming compensation for noise-induced hearing loss (NIHL). When present and otherwise unexplained, there is some controversy as to whether such asymmetry can be attributed to occupational noise exposure. In this review, our main objectives were to collate the overall prevalence of this finding in subjects with NIHL, and further, to provide a balanced argument regarding causality. DATA SOURCES: MEDLINE, CINAHL, EMBASE, Cochrane, Google Scholar. No date or language restrictions. STUDY SELECTION AND DATA EXTRACTION: A systematic review of the literature was performed and data on noise exposure, pure tone audiometry, and lateralized hearing outcomes were reviewed. Newcastle-Ottawa (N-O) criteria were employed to assess quality of studies where applicable. DATA SYNTHESIS: N/A CONCLUSION:: Six studies met the inclusion criteria giving a total of 4,735 individual cases with NIHL. Asymmetrical hearing loss accounted for between 2.4% and 22.6% of NIHL cases (L-R difference >15 dB for any frequency 0.5-8 kHz). However, the overwhelming majority of subjects in this review have symmetrical hearing loss when adjusted for other significant variables, e.g., age, sex, and binaural hearing deterioration. Subjects considered for noise exposure remuneration were men (94.3% SE +/- 2.7), aged 52.9 years (inter-quartile range, 46.1-58.4), and from a broad range of industrial backgrounds. Future research will be needed to establish the influence of other factors such as smoking status, exposure to chemical agents, specific drugs, or genetic predisposition. PMID- 27273400 TI - The Association of Valsalva Status With Smoking and Its Impact on Ossiculoplasty Outcomes and Complications. AB - OBJECTIVES: To assess the association of a patient's ability to perform a clinically observed Valsalva maneuver with tobacco smoking and post ossiculoplasty outcomes. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral, university-based otology practice. PATIENTS: Adult patients (16-88 years of age) undergoing ossiculoplasty with tympanoplasty or tympanomastoidectomy using cartilage tympanic membrane grafts, retrograde mastoidectomy with canal wall reconstruction, or mastoid obliteration techniques. OUTCOME MEASURES: Patients were classified as Valsalva negative (Val) or positive (Val). Comparisons were then made between these two groups for smoking status, final audiometric outcomes, rate of cure of conductive hearing loss, anatomic outcomes, and incidence of significant complications after otologic surgery involving ossiculoplasty. RESULTS: Tobacco smoking is not significantly correlated with the inability to insufflate the middle ear with the Valsalva maneuver (p = 0.557). An insignificant difference in final pure-tone average air bone gap (PTA-ABG) was observed between the Val and Val groups (20.2 dB HL versus 18.2 dB HL, respectively; p = 0.152). Similarly, the rate of successful PTA-ABG closure to <=20 dB HL was not significantly different between the groups (62.5% [80 of 128] of Val patients and 56.8% [54 of 95] of Val patients [p = 0.394]). Postoperative complications were seen with a higher frequency in the Val patients (16.8% [16 of 95] versus 7.0% [9 of 128]; p = 0.022). CONCLUSIONS: A patient's inability to perform the Valsalva maneuver is not significantly associated with smoking; however, negative Valsalva status is associated with an increased incidence of significant complications after ossiculoplasty. PMID- 27273401 TI - Botulinum Toxin Treatment of Objective Tinnitus Because of Essential Palatal Tremor: A Systematic Review. AB - INTRODUCTION: In contrast to subjective tinnitus, objective tinnitus can be heard by the examiner as well as by the patient. It can be triggered by, among many other etiologies, idiopathic muscular tremor in the soft palate, the essential palatal tremor (EPT). Many treatment modalities have been investigated, of which only Botulinum toxin (BT) injections have shown promising results. GOAL: The aim of this study was to evaluate the effect of BT treatment on objective tinnitus due to EPT by a systematic review of the literature. METHODS: In accordance with PRISMA guideline a systematic literature search in three databases was performed. RESULTS: Twenty-two studies fulfilled the inclusion criteria, mainly case reports and case series. A total of 51 BT treated patients diagnosed with EPT were identified in the literature. The studies were evaluated with focus on diagnostics, injection technique and BT dose, follow-up, effect on objective tinnitus, complications, and adverse effects. CONCLUSIONS: The included studies suffer from an extremely low evidence level with several sources of bias. When optimally injected, BT seems to be an effective treatment of objective tinnitus due to EPT, with few adverse effects and complications. We suggest BT injections as first choice in case of EPT and present a guideline regarding diagnostics, treatment, and follow-up. PMID- 27273402 TI - A Systematic Review on Complications of Tissue Preservation Surgical Techniques in Percutaneous Bone Conduction Hearing Devices. AB - OBJECTIVE: To investigate skin-related postoperative complications from tissue preservation approaches in percutaneous bone conduction device (BCD) implantations. DATA SOURCES: PubMed, Embase, and Cochrane Library. STUDY SELECTION: We identified studies on BCDs including the opted surgical technique and derived complications. Retrieved articles were screened using predefined inclusion criteria. Critical appraisal included directness of evidence and risk of bias. Studies that successfully passed critical appraisal were included. DATA EXTRACTION: Outcome measures included patient demographics, surgery time, follow up time, and complications reported by Holgers classification. DATA SYNTHESIS: We selected 18 articles for data extraction; encompassing 381 BCDs implanted using non-skin thinning approaches. Four studies reported an implantation technique using the punch method (81 implants), 13 studies applied the linear incision technique without soft tissue reduction (288 implants) and one study used the Weber technique (12 implants). Holgers 3 was described in 2.5% following the punch technique, in 5.9% following the linear incision technique, and in no implants following the Weber technique. One patient was mentioned having Holgers 4, skin overgrowth was reported in 6 patients, and 10 studies compared their non skin thinning technique with a skin-thinning technique. Overall, the soft tissue preservation technique had a similar or superior complication rate, shorter surgical time, and better and faster healing, compared with the soft tissue reduction technique. CONCLUSION: Tissue preservation surgical techniques for percutaneous BCDs have limited postoperative skin complication rates. Moreover, these techniques are suggested to have at least similar complications rates compared with skin-thinning techniques. PMID- 27273403 TI - Petroclival Chondrosarcoma: A Multicenter Review of 55 Cases and New Staging System. AB - OBJECTIVE: To analyze clinical outcomes after treatment of petroclival chondrosarcoma and to propose a novel staging system. STUDY DESIGN: Retrospective case review, 1995 to 2015. SETTING: Multicenter study. PATIENTS: Consecutive patients with histopathologically proven petroclival chondrosarcoma. INTERVENTION(S): Microsurgery, endoscopic endonasal surgery, radiation therapy, observation. MAIN OUTCOME MEASURES: Disease- and treatment-associated morbidity, recurrence, mortality. RESULTS: Fifty-five patients (mean age 42 years; 56% women) presenting with primary or recurrent petroclival chondrosarcoma were analyzed. The mean duration of follow-up was 74 months. Among 47 primary cases, the most common presenting symptoms were headache (55%) and diplopia (49%) and the mean tumor size at diagnosis was 3.3 cm. Subtotal resection was performed in 33 (73%) patients and gross total resection in 12 (27%). Adjuvant postoperative radiation was administered in 30 (64%) cases. Preoperative cranial neuropathy improved in 13 (29%), worsened in 11 (24%), and remained stable in 21 (47%) patients; notably, 11 preoperative sixth nerve palsies resolved after treatment. Nine recurrences occurred at a mean of 42 months. The 1-, 3-, 5- and 10-year recurrence-free survival rate for all 45 patients who underwent primary microsurgery with or without adjuvant radiation therapy was 97%, 89%, 70%, and 56%, respectively. Higher tumor stage, larger categorical size (<4 versus >=4 cm), lack of adjuvant radiation, and longer duration of follow-up were associated with greater risk of recurrence. The overall mortality rate was 2% for patients presenting with primary disease.Analyzing the cohort of 17 cases with 20 recurrences, 3 received salvage surgery alone, 5 radiation therapy alone, 11 multimodality treatment, and one patient has been observed. Tumor control was ultimately achieved in 15 of 17 patients with recurrent disease. One patient (6%) with grade 3 petroclival chondrosarcoma died as a result of rapidly progressive disease within 6 months of salvage treatment. The overall mortality rate was 6% for patients with recurrent disease. CONCLUSION: Gross total or subtotal resection with adjuvant radiation provides durable tumor control with minimal morbidity in most patients. Surgery may improve preoperative cranial nerve dysfunction, particularly in the case of cranial nerve 6 paralysis. PMID- 27273404 TI - TeleAudiology in the Veterans Health Administration. AB - OBJECTIVE: To assess effectiveness of TeleAudiology for hearing aid services. STUDY DESIGN: Retrospective case-control. SETTING: Ambulatory Veterans Health Administration and Community-Based Outpatient Clinics (CBOCs). PATIENTS: 42,697 veterans who received hearing aids from January through September, 2014. INTERVENTION(S): TeleAudiology (TA) and conventional in-person (IP) audiology care. MAIN OUTCOME MEASURE(S): International Outcome Inventory for Hearing Aids (IOI-HA) outcomes data. The IOI-HA is a 7-item survey used to assess hearing aid effectiveness. Scored from 7 to 35 points, higher scores are more favorable. RESULTS: Among veterans nationwide who received hearing aids and completed the IOI-HA survey, 1,009 received TA and 41,688 received IP care. TA and IP groups have comparable mean IOI-HA values (TA = 29.6, SD = 3.9; IP = 28.7, SD = 4.2). Although comparison showed a statistically significant difference (p < 0.0001, t test), principally because of large sample size, the distinction is not clinically meaningful.Subgroup analysis of veterans from San Francisco and six affiliated CBOCs showed 169 received TA and 338 received IP care. TA and IP groups have similar mean age (TA = 74, SD = 9.8; IP = 76, SD = 10.3) and sex distribution (TA male = 100%; IP male = 96%) with statistically significant (p < 0.01, t test) but clinically insignificant differences. Mean IOI-HA scores (TA = 30.7, SD = 3.6; IP = 30.5, SD = 3.1) are not different between groups (p > 0.05, t test). CONCLUSION: TA and IP encounters to provide hearing aid services to veterans are comparable, as both are highly effective based on IOI-HA results. The noninferiority of TA suggests its adoption to non-veterans may improve access while preserving high satisfaction. Financial impact of migration to TA will require future econometric analysis. PMID- 27273405 TI - Type I Tympanoplasty Meta-Analysis: A Single Variable Analysis. AB - OBJECTIVE: To determine which independent variables influence the efficacy of type I tympanoplasty in adult and pediatric populations. DATA SOURCES: A search of the PubMed database and Cochrane Database of Systematic Reviews using the key words "tympanoplasty OR myringoplasty" from January 1966 to July 2014 was performed. STUDY SELECTION: Studies reporting outcomes of myringoplasty or Type I tympanoplasty in primary non-cholesteatomatous chronic tympanic membrane (TM) perforation were included. DATA EXTRACTION: Of 4,698 abstracts reviewed, 214 studies involving 26,097 patients met our inclusion criteria and contributed to meta-analysis. DATA SYNTHESIS: The primary outcome of success was defined as closure rate at 12 months. The independent variables analyzed were age, follow-up period, approach, graft material, perforation cause, size, location, ear dryness, and surgical technique. Only those studies providing data on a given parameter of interest could be included when comparing each variable. CONCLUSION: The weighted average success rate of tympanic closure was 86.6%. Based on this meta-analysis, pediatric surgery has a 5.8% higher failure rate than adults and there is no correlation between follow-up period and success. Other variables associated with improved closure rates include perforation with a size less than 50% of total area (improved by 6.1%) and the use of cartilage as a graft (improved by 2.8% compared with fascia), while ears that were operated on while still discharging, those in different locations of the pars tensa, or using different surgical approaches or techniques did not have significantly different outcomes. PMID- 27273407 TI - Cochlear Implantation in Patients With Intracochlear and Intralabyrinthine Schwannomas. AB - OBJECTIVE: Schwannomas may arise primarily within the inner ear, or invade the cochlea or labyrinth from the distal internal auditory canal through transmodiolar or transmacular extension, respectively. To date, very limited data exists regarding cochlear implant (CI) outcomes in this unique population. STUDY DESIGN: Retrospective case review. PATIENTS: Ten ears (nine patients) with inner ear schwannomas that underwent CI at a single tertiary referral center. INTERVENTION(S): Cochlear implantation. MAIN OUTCOME MEASURE(S): Surgical approach, CI performance. RESULTS: Ten ears (nine patients) were implanted with conventional CI arrays. Three cases had primary inner ear schwannomas, while seven were in patients with neurofibromatosis type 2 (NF2) having transmodiolar invasion of the inner ear from a vestibular schwannoma (VS). In all cases, intracochlear tumor was left in situ to preserve cochlear anatomy and a full electrode insertion was achieved. Use of a styleted electrode with late deployment aided advancement through the intracochlear tumor. In all cases, the ipsilateral internal auditory canal and inner ear could be visualized on postoperative magnetic resonance imaging (MRI) for tumor surveillance. Eight ears achieved good open-set word recognition (median, Consonant-Nucleus-Consonant [CNC] 50% [range, 28-88%], median, AzBio 73% [range, 60-91%]); two patients with NF2 and prolonged deafness (15 and 22 years) received limited benefit. CONCLUSIONS: Cochlear implantation in patients with inner ear schwannomas and an intact cochlear nerve is feasible. Leaving intracochlear schwannoma in situ preserves cochlear architecture and use of a styleted electrode may aid in achieving a full insertion when obstructing tumor is present. Postoperative MRI surveillance is still adequate after CI and a high percentage of patients achieve good open-set speech perception performance. PMID- 27273406 TI - Cochlear Histopathology as Observed in Two Patients With a Cochlear Implant Electrode With Positioner. AB - HYPOTHESIS: This study reports the cochlear histopathology of two patients who during life underwent cochlear implantation with a positioner. BACKGROUND: A silastic positioner introduced by the Advanced Bionics Corporation in 1999 was designed to position the electrode of the cochlear implant close to the modiolus. The positioner was recalled in the United States in July 2002 because of an apparent higher incidence of bacterial meningitis in patients in whom the positioner had been placed. METHODS: Four celloidin-embedded temporal bones from two patients with cochlear implants with a positioner from the temporal bone collection of the Massachusetts Eye and Ear Infirmary were included in the study. In a previous study, we reported histopathologic findings in Patient 1, and in this report, we present the findings in a second case in a 94-year-old woman (Patient 2), and the similarities and differences between the two patients. All four specimens were prepared for histologic study by conventional techniques and 2-D reconstruction. RESULTS: Evidence of insertion trauma was observed in all three implanted specimens. More significant trauma was found in Patient 2 than in Patient 1 including disruption of the osseous spiral lamina and the basilar membrane. In addition, there was more new fibrous tissue and bone in Patient 2 than in Patient 1. There was a large fluid space in all three implanted temporal bones around the electrode and positioner. CONCLUSION: The findings observed in the two patients may help to explain the increased risk of meningitis in patients implanted with a positioner. PMID- 27273409 TI - Issues for the Traveling Team Physician. AB - This article outlines the value of having the team physician traveling with athletes to away venues for competitions or training sessions. At present, this travel presents several issues for the team physician who crosses state lines for taking care of the athletes. In this article, these issues and their possible remedies are discussed. A concern for the travelling team physician is practicing medicine while caring for the team in a state where the physician is not licensed. Another issue can be the transportation of controlled substances in the course of providing optimal care for the team athletes. These two issues are regulatory and legislative issues at both the state and federal levels. On the practical side of being a team physician, the issues of emergency action plans, supplies, and when to transport injured or ill patients are also reviewed. PMID- 27273408 TI - Focal Endolymphatic Hydrops as Seen in the Pars Inferior of the Human Inner Ear. AB - HYPOTHESIS: Endolymphatic hydrops of the human inner ear may be localized focally in the pars inferior of the human inner ear. BACKGROUND: Endolymphatic hydrops may be found in the human inner ear in patients who in life had suffered from Meniere's syndrome or a variety of other disorders. The degree of endolymphatic hydrops may differ based on location in the inner ear. METHODS: A computer assisted search of all cases in the collection of the Massachusetts Eye and Ear Infirmary in which endolymphatic hydrops was found in the inner ear yielded 13 specimens in which there was good evidence for focal endolymphatic hydrops in the pars inferior. Temporal bones were prepared for light microscopy. Semi-serial sections were reviewed to generate localization data for endolymphatic hydrops and also to search for evidence of a previous inflammatory process, including fibrosis or new bone formation. RESULTS: Endolymphatic hydrops was present in the saccule in 10 of 13 specimens. In the cochlear duct, there were segments of the cochlea in which there was no cochlear hydrops juxtaposed to other regions in which there was severe endolymphatic hydrops. Transition between hydropic and non hydropic status in the cochlear duct was often abrupt.Evidence for a previous inflammation process was found in 6 of 13 specimens including fibrosis because of temporal bone fracture, or traumatic stapedectomy and in those cases in which the cause of hearing loss was idiopathic, fibrosis, and osteoid between the labyrinthine surface of the footplate and the hydropic saccular wall, and/or osteoid in the scala vestibuli, or in the proximate Rosenthal's canal. Evidence of a previous inflammatory process was uniformly seen in the perilymphatic compartment. CONCLUSIONS: Endolymphatic hydrops of the pars inferior in the human may have a focal distribution. This study suggests that the pathogenesis of endolymphatic hydrops is unlikely to be because of distal obstruction of longitudinal flow and was more consistent with the hypothesis that homeostasis of the endolymphatic and perilymphatic volumes occurs all along the cochlear duct. Other factors including variable distensibility of Reissner's membrane or disturbance of local solute homeostatic mechanisms may be responsible for wide variations in the degree of hydrops. A focal inflammatory process during life may be one cause of focal endolymphatic hydrops as seen histopathologically. PMID- 27273411 TI - Functional lipids based on [12]aneN3 and naphthalimide as efficient non-viral gene vectors. AB - Small organic non-viral gene vectors with the structural combinations of (aliphatic chain)-naphthalimide-[12]aneN3 (11a, b) and naphthalimide-(aliphatic chain)-[12]aneN3 (12a-c) were synthesized and fully characterized. Agarose gel electrophoresis experiments indicated that the first type of compounds, 11a and 11b, could completely retard DNA at the concentration of 5 MUM in the presence of DOPE. Within the second type of compounds, 12c with the decane chain showed a complete retardation of DNA at the concentration of 20 MUM, whereas 12a and 12b with the ethyl and hexyl chains could not retard DNA effectively. Dynamic light scattering measurements indicated that compounds 11a, 11b and 12b, 12c condensed DNA into nanoparticles with the size in the range of 60-160 nm. Due to the strong fluorescence of 11a and 11b, the distribution of lipids/DNA complexes and the process of DNA release from the lipids were clearly observed via cellular uptake experiments. On the other hand, the non-fluorescent 12a-c enabled the EB exclusion assay to afford the binding constants of 4.88 * 10(6) M(-1) (12a), 4.18 * 10(6) M(-1) (12b) and 3.39 * 10(6) M(-1) (12c), respectively. The MTT assay revealed that both types of compounds have low cytotoxicity. Non-fluorescent 12c was successfully applied in the eGFP expression experiments in A549 cells and showed stronger green fluorescence emission than that of lipofectamine 2000. Quantitative transfection experiments through the luciferase assay further revealed that compounds 11a, 11b and 12c can act as non-viral gene vectors in different cell lines. Among them, 12c gave the highest transfection efficiency in HeLa cells, which was about 2 times that offered by lipofectamine 2000. This work clearly demonstrated that the right combination of different functional units and long aliphatic linkers will likely promote gene delivery and transfection efficiency. PMID- 27273422 TI - 2016 American Transplant Congress Abstracts. PMID- 27273421 TI - Fast formation and growth of high-density Sn whiskers in Mg/Sn-based solder/Mg joints by ultrasonic-assisted soldering: Phenomena, mechanism and prevention. AB - A universally applicable method for promoting the fast formation and growth of high-density Sn whiskers on solders was developed by fabricating Mg/Sn-based solder/Mg joints using ultrasonic-assisted soldering at 250 degrees C for 6 s and then subjected to thermal aging at 25 degrees C for 7 d. The results showed that the use of the ultrasonic-assisted soldering could produce the supersaturated dissolution of Mg in the liquid Sn and lead to the existence of two forms of Mg in Sn after solidification. Moreover, the formation and growth of the high-density whiskers were facilitated by the specific contributions of both of the Mg forms in the solid Sn. Specifically, interstitial Mg can provide the persistent driving force for Sn whisker growth, whereas the Mg2Sn phase can increase the formation probability of Sn whiskers. In addition, we presented that the formation and growth of Sn whiskers in the Sn-based solders can be significantly restricted by a small amount of Zn addition (>=3 wt.%), and the prevention mechanisms are attributed to the segregation of Zn atoms at grain or phase boundaries and the formation of the lamellar-type Zn-rich structures in the solder. PMID- 27273423 TI - Lack of transparency in software used to analyze multiple breath washout data. PMID- 27273424 TI - Bioavailability and metabolism of phenolic compounds from wholegrain wheat and aleurone-rich wheat bread. AB - SCOPE: This work aimed at investigating absorption, metabolism, and bioavailability of phenolic compounds after consumption of wholegrain bread or bread enriched with an aleurone fraction. METHODS AND RESULTS: Two commercially available breads were consumed by 15 participants on three occasions and matched for either the amount of ferulic acid in the bread or the amount of bread consumed. Urine was collected for 48 h from all the volunteers for phenolic metabolite quantification. Blood samples were collected for 24 h following bread consumption in five participants. A total of 12 and 4 phenolic metabolites were quantified in urine and plasma samples, respectively. Metabolites were sulfate and glucuronic acid conjugates of phenolic acids, and high concentrations of ferulic acid-4'-O-sulfate, dihydroferulic acid-4'-O-sulfate, and dihydroferulic acid-O-glucuronide were observed. The bioavailability of ferulic acid was significantly higher from the aleurone-enriched bread when all ferulic acid metabolites were accounted for. CONCLUSIONS: The study shows that low amounts of aleurone-enriched bread resulted in equivalent plasma levels of ferulic acid as wholegrain bread. This could suggest that, if the absorbed phenolic metabolites after wholegrain product intake exert health benefits, equal levels could be reached through the consumption of lower doses of refined products enriched in aleurone fraction. PMID- 27273425 TI - Rapid assessment of salivary MMP-8 and periodontal disease using lateral flow immunoassay. AB - OBJECTIVE: The objective of this study was to determine the efficacy of a novel point-of-care immunoflow device (POCID) for detecting matrix metalloproteinase (MMP)-8 concentrations in oral fluids in comparison with a gold standard laboratory-based immunoassay. METHODS: Oral rinse fluid and whole expectorated saliva samples were collected from 41 participants clinically classified as periodontally healthy or diseased. Samples were analyzed for MMP-8 by Luminex immunoassay and POCID. Photographed POCID results were assessed by optical scan and visually by two examiners. Data were analyzed by Pearson's correlation and receiver-operating characteristics. RESULTS: MMP-8 was readily detected by the POCID, and concentrations correlated well with Luminex for both saliva and rinse fluids (r = 0.57-0.93). Thresholds that distinguished periodontitis from health were delineated from both the optical scans and visual reads of the POCID (sensitivity: 0.7-0.9, specificity: 0.5-0.7; P < 0.05). CONCLUSIONS: Performance of this POCID for detecting MMP-8 in oral rinse fluid or saliva was excellent. These findings help demonstrate the utility of salivary biomarkers for distinguishing periodontal disease from health using a rapid point-of-care approach. PMID- 27273426 TI - Nanodiamond-based nanostructures for coupling nitrogen-vacancy centres to metal nanoparticles and semiconductor quantum dots. AB - The ability to control the interaction between nitrogen-vacancy centres in diamond and photonic and/or broadband plasmonic nanostructures is crucial for the development of solid-state quantum devices with optimum performance. However, existing methods typically employ top-down fabrication, which restrict scalable and feasible manipulation of nitrogen-vacancy centres. Here, we develop a general bottom-up approach to fabricate an emerging class of freestanding nanodiamond based hybrid nanostructures with external functional units of either plasmonic nanoparticles or excitonic quantum dots. Precise control of the structural parameters (including size, composition, coverage and spacing of the external functional units) is achieved, representing a pre-requisite for exploring the underlying physics. Fine tuning of the emission characteristics through structural regulation is demonstrated by performing single-particle optical studies. This study opens a rich toolbox to tailor properties of quantum emitters, which can facilitate design guidelines for devices based on nitrogen vacancy centres that use these freestanding hybrid nanostructures as building blocks. PMID- 27273427 TI - Mini-MACS: development of the Manual Ability Classification System for children younger than 4 years of age with signs of cerebral palsy. AB - AIM: To develop the Mini-Manual Ability Classification System (Mini-MACS) and to evaluate the extent to which its ratings are valid and reliable when children younger than 4 years are rated by their parents and therapists. METHOD: The Mini MACS was created by making adjustments to the MACS. The development involved a pilot project, consensus discussions within an expert group, and the creation of a test version of the Mini-MACS that was evaluated for content validity and interrater reliability. A convenience sample of 61 children with signs of cerebral palsy aged 12 to 51 months (mean age 30.2mo [SD 10.1]) were classified by one parent and two occupational therapists across a total of 64 assessments. Agreement between the parents' and therapists' ratings was evaluated using the intraclass correlation coefficient (ICC) and the percentage of agreement. RESULTS: The first sentence of the five levels in the MACS was kept, but other descriptions within the Mini-MACS were adjusted to be more relevant for the younger age group. The ICC between parents and therapists was 0.90 (95% confidence interval [CI] 0.79-0.92), and for the two therapists it was 0.97 (95% CI 0.78-0.92). Most parents and therapists found the descriptions in the Mini MACS suitable and easy to understand. INTERPRETATION: The Mini-MACS seems applicable for children from 1 to 4 years of age. PMID- 27273429 TI - Estimated Cost of Injectable Medication Waste Attributable to Syringe Dead Space. PMID- 27273428 TI - p120-catenin is necessary for neuroprotection induced by CDK5 silencing in models of Alzheimer's disease. AB - Cyclin-dependent kinase 5 (CDK5) plays important roles in synaptic function. Its unregulated over-activation has been, however, associated with neurodegeneration in Alzheimer's disease. Our previous studies revealed that CDK5 silencing ameliorates tauopathy and spatial memory impairment in the 3xTgAD mouse model. However, how CDK5 targeting affects synaptic adhesion proteins, such as those involved in the cadherin/catenin system, during learning and memory processes is not completely understood. In this study, we detected reduced expression of p120 catenin (p120 ctn), N-cadherin, and beta-catenin in the brain of human Alzheimer's disease patients, in addition to a reduced PSD95 and GluN2B protein levels in a 3xTgAD mouse model. Such decrease in synaptic proteins was recovered by CDK5 silencing in mice leading to a better learning and memory performance. Additionally, CDK5 inhibition or knockout increased p120 ctn levels. Moreover, in a glutamate-induced excitotoxicity model, CDK5 silencing-induced neuroprotection depended on p120 ctn. Together, those findings suggest that p120 ctn plays an important role in the neuronal dysfunction of Alzheimer's disease models and contributes to CDK5 silencing-induced neuroprotection and improvement of memory function. p120ctn is part of the synaptic adhesion molecular complex N cadh/p120ctn/B-ctn/PSD95, and it has a pivotal role in cell adhesion stabilization and dendritic spine modulation. Our data show that synaptic adhesion complex is affected in AD human brains and in AD models. This complex is recovered by the silencing of CDK5, preventing memory dysfunction in an AD mice model and contributing to the neuroprotection in a depend-mode of p120ctn. PMID- 27273430 TI - Imaging unstable plaque. AB - Recent advances in imaging technology have enabled us to utilise a range of diagnostic approaches to better characterise high-risk atherosclerotic plaque. The aim of this article is to review current and emerging techniques used to detect and quantify unstable plaque in the context of large and small arterial systems and will focus on both invasive and non-invasive imaging techniques. While the diagnosis of clinically relevant atherosclerosis still relies heavily on anatomical assessment of arterial luminal stenosis, evolving multimodal cross sectional imaging techniques that encompass novel molecular probes can provide added information with regard to plaque composition and overall disease burden. Novel molecular probes currently being developed to track precursors of plaque rupture such as inflammation, micro-calcification, hypoxia and neoangiogenesis are likely to have translational applications beyond diagnostics and have the potential to play a part in quantifying early responses to therapeutic interventions and more accurate cardiovascular risk stratification. PMID- 27273431 TI - Inflammation: a trigger for acute coronary syndrome. AB - Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis' most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes. PMID- 27273433 TI - Study of the Atopic March: Development of Atopic Comorbidities. AB - BACKGROUND: Atopic dermatitis (AD) is often the first step in the atopic march leading to the development of asthma or allergic rhinitis. The goal of this study was to determine whether early intervention with pimecrolimus limits the atopic march in infants with AD and to evaluate its efficacy and safety. METHODS: This was a 3-year double-blind study in which patients were randomized to pimecrolimus or vehicle and then open-label pimecrolimus for a planned further 3 years. Rescue topical corticosteroid was permitted if 3 days of study medication led to no improvement; investigators made decisions on rescue medication until week 14 and caregivers thereafter. Efficacy assessments included disease-free days, Eczema Area and Severity Index, and body surface area affected. RESULTS: Infants ages 3 to 18 months with recent-onset AD (<=3 months) were observed for a mean of 2.8 years (N = 1,091). No significant differences between pimecrolimus- and placebo treated groups were found in the percentage of patients with AD who developed asthma (10.7%) or other allergic conditions (allergic rhinitis, 22.4%; food allergy, 15.9%; allergic conjunctivitis, 14.1%; one or more atopic comorbidities, 37.0%) by study end. Allergic rhinitis, food allergy, and having one or more atopic comorbidities (but not asthma or allergic conjunctivitis alone) developed significantly more often in infants with greater AD severity at baseline. Pimecrolimus was significantly more effective than vehicle for AD treatment at week 14. Adverse event incidences were similar. CONCLUSIONS: This longitudinal observation of infants with AD provides evidence of the atopic march. Pimecrolimus was safe and effective in infants with mild to moderate AD. PMID- 27273434 TI - Effectiveness of subarachnoid drug infusion for pediatric tumor-related pain. AB - Although the effectiveness of subarachnoid continuous drug infusion has been established in cancer pain management, its clinical use in children is rare. A 14 year-old girl with neurofibromatosis type I complained of right leg pain stemming from a growing tumor on her right buttock. Continuous and breakthrough right leg pain were unbearable, even at high doses of systemic opioids that caused severe constipation and deep sedation. Subsequent continuous infusion of bupivacaine and morphine through a subarachnoid catheter effectively relieved the girl's pain. The corresponding decrease in systemic opioid also improved her activities of daily living. The patient eventually died of cachexia due to the rapidly growing buttock lesion that was pathologically confirmed post-mortem as a malignant peripheral nerve sheath tumor. Subarachnoid continuous drug infusion may be very useful in controlling severe pain with few side-effects, even in the field of pediatric palliative care. PMID- 27273435 TI - Patterns of long-term care services use in a suburban municipality of Japan: a population-based study. AB - AIM: Increasing service use under the long-term care insurance (LTCI) system in Japan requires a comprehensive understanding of how the services are actually used. This study aimed to identify patterns of LTCI service use and to examine the characteristics of the patterns. METHODS: We analyzed data from a population of 4,339 older adults living in the community who were certified as "Needing Care" and were using at least one LTCI service in a suburban municipality of Japan. We identified six patterns of service use using cluster analysis based on the amount of fees for LTCI services and compared characteristics among the clusters. RESULTS: The clusters were: 1) light use of care services (n = 1,852); 2) day care-centered (n = 1,071); 3) day care with rehabilitation-centered (n = 616); 4) home help-centered (n = 365); 5) short-stay respite service-centered (n = 246); and 6) compound uses of visiting services (n = 189). "Home help-centered" and "short-stay respite service-centered" clusters used a large number of fees, whereas "compound uses of visiting services" clusters did not despite their severe conditions. The "day care-centered (with rehabilitation)" classification included few people who needed medical procedures, likely due to the lack of medical facilities in those agencies. CONCLUSIONS: The results show the impact of social and medical factors on LTCI service use, suggesting possible difficulties in the socialization of care. The clusters could be used as typical service use patterns, providing a framework for further studies, such as those evaluating the services' effects. Geriatr Gerontol Int 2017; 17: 753-759. PMID- 27273432 TI - Human glia can both induce and rescue aspects of disease phenotype in Huntington disease. AB - The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder. PMID- 27273436 TI - 3D Printing: 3D Printing of Shape Memory Polymers for Flexible Electronic Devices (Adv. Mater. 22/2016). AB - On page 4449, D. Cohn, S. Magdassi, and co-workers describe a general and facile method based on 3D printing of methacrylated macromonomers to fabricate shape memory objects that can be used in flexible and responsive electrical circuits. Such responsive objects can be used in the fabrication of soft robotics, minimal invasive medical devices, sensors, and wearable electronics. The use of 3D printing overcomes the poor processing characteristics of thermosets and enables complex geometries that are not easily accessible by other techniques. PMID- 27273438 TI - Flexible and Stretchable Devices. PMID- 27273440 TI - Electroluminescent Devices: Extremely Stretchable Electroluminescent Devices with Ionic Conductors (Adv. Mater. 22/2016). AB - An extremely stretchable electroluminescent device is fabricated by P. S. Lee and co-workers, as described on page 4490. The stretchable alternating-current electroluminescent (ACEL) device possesses extremely high stretchability, and can be linearly stretched to 700% with the luminance being maintained at 70% of the initial value before stretching. The device can be repeatedly stretched to 400% with stable emission behavior. The presented device will provide new opportunities in stretchable lighting, volumetric 3D displays, interactive readout systems, and other unprecedented applications. PMID- 27273441 TI - Biphasic Metal Films: Intrinsically Stretchable Biphasic (Solid-Liquid) Thin Metal Films (Adv. Mater. 22/2016). AB - On page 4507, S. P. Lacour and co-workers present highly conductive and stretchable solid-liquid films that are formed by physical vapor deposition of gallium onto an alloying gold layer. The image shows patterns defined by lift-off on an elastomer membrane. The magnified view is a false-color scanning electron microscopy (SEM) image (*5000) of the surface of the films under 50% applied strain, showing the liquid Ga (blue-gray) flowing between the AuGa2 /Ga clusters (gold). PMID- 27273439 TI - Carbon Nanotubes: Printed Carbon Nanotube Electronics and Sensor Systems (Adv. Mater. 22/2016). AB - Printed electronics and sensors enable new applications ranging from low-cost disposable analytical devices to large-area sensor networks. Recent progress in printed carbon nanotube electronics in terms of materials, processing, devices, and applications is discussed on page 4397 by A. Javey and co-workers. The research challenges and opportunities regarding the processing and system-level integration are also discussed for enabling of practical applications. PMID- 27273442 TI - Flexible Electronics: An Epidermal Stimulation and Sensing Platform for Sensorimotor Prosthetic Control, Management of Lower Back Exertion, and Electrical Muscle Activation (Adv. Mater. 22/2016). AB - The design of an ultrathin, conformal electronic device that integrates electrotactile stimulation with electromyography, temperature, and strain sensing in a single, simple platform is reported by J. A. Rogers and co-workers on page 4462. Demonstrated application possibilities include prosthetic control with sensory feedback, monitors, and stimulation signals related to lower back exertion, and electrical muscle stimulation with feedback control. PMID- 27273443 TI - Deformable Electronics: Conducting Polymer Dough for Deformable Electronics (Adv. Mater. 22/2016). AB - A simple strategy for changing a brittle conducting polymer ( PEDOT: PSS) into a solution-processed highly deformable viscoelastic polymer is presented by H.-K. Baik, U. Jeong, and co-workers on page 4455. The storage modulus versus loss modulus of the polymer is adjusted to control the viscoelastic properties to fit the properties required in deformable electronics. Rapid self-healing of conductivity, custom-designed LEDs with complex micropatterns, and foldable stretchable LEDs are demonstrated. PMID- 27273447 TI - Development of a control algorithm for the ultrasound scanning robot (NCCUSR) using ultrasound image and force feedback. AB - BACKGROUND: Clinicians who frequently perform ultrasound scanning procedures often suffer from musculoskeletal disorders, arthritis, and myalgias. To minimize their occurrence and to assist clinicians, ultrasound scanning robots have been developed worldwide. Although, to date, there is still no commercially available ultrasound scanning robot, many control methods have been suggested and researched. These control algorithms are either image based or force based. If the ultrasound scanning robot control algorithm was a combination of the two algorithms, it could benefit from the advantage of each one. However, there are no existing control methods for ultrasound scanning robots that combine force control and image analysis. Therefore, in this work, a control algorithm is developed for an ultrasound scanning robot using force feedback and ultrasound image analysis. METHODS: A manipulator-type ultrasound scanning robot named 'NCCUSR' is developed and a control algorithm for this robot is suggested and verified. First, conventional hybrid position-force control is implemented for the robot and the hybrid position-force control algorithm is combined with ultrasound image analysis to fully control the robot. The control method is verified using a thyroid phantom. RESULTS: It was found that the proposed algorithm can be applied to control the ultrasound scanning robot and experimental outcomes suggest that the images acquired using the proposed control method can yield a rating score that is equivalent to images acquired directly by the clinicians. CONCLUSIONS: The proposed control method can be applied to control the ultrasound scanning robot. However, more work must be completed to verify the proposed control method in order to become clinically feasible. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273448 TI - Povidone-iodine is still a premium antiseptic measure in ocular surgery. PMID- 27273449 TI - Towards 1D nanolines on a monolayered supramolecular network adsorbed on a silicon surface. AB - The growth of 3D extended periodic networks made up of pi-conjugated molecules on semi-conductor surfaces is of interest for the integration of nano-components in the future generations of smart devices. In the work presented in this article, we successfully achieved the formation of bilayered networks on a silicon surface including 1D-isolated nanolines in the second layer. Firstly, we observed the formation of a 2D large-scale supramolecular network in the plane of a silicon surface through the deposition of tailored molecules. Then using the same molecules, a second-layer, based on 1D nanolines, grew above the first layer, thanks to a template effect. Mono- or bi-layered networks were found to be stable from 100 K up to room temperature. These networks were investigated by scanning tunnel microscopy imaging under an ultra-high vacuum (UHV-STM). PMID- 27273451 TI - Identification of IgE and IgG epitopes on native Bos d 4 allergen specific to allergic children. AB - Alpha-lactalbumin (ALA) is one of the major allergens in cow's milk. However, research on its conformational epitopes has been relatively limited. In our study, specific antibodies against cow's milk ALA were purified from eight children by two-step affinity chromatography. Subsequently, mimotopes against IgG and IgE were biopanned from Ph.D.-12 and Ph.D.-C7C, respectively. Based on the mimotopes, linear epitopes were defined with the UniProt alignment tool. Conformational epitopes were computed using the Pepitope Server. Six IgE and seven IgG linear epitopes were identified. Meanwhile, five IgE and three IgG conformational epitopes were revealed with PyMOL. The results showed that common residues were identified in both IgE and IgG epitopes and some residues of the conformational epitopes were composed of linear epitopes on bovine alpha lactalbumin. The results indicated that the data could be used for developing hypoallergenic dairy products on the basis of epitopes and providing a diagnostic tool for the assessment of patients who are allergic to cow's milk. PMID- 27273452 TI - Syphilis Screening Recommendation in Nonpregnant Adults and Adolescents: Still Waters Run Deep. PMID- 27273450 TI - CRAF R391W is a melanoma driver oncogene. AB - Approximately 75% of melanomas have known driver oncogenic mutations in BRAF, NRAS, GNA11 or GNAQ, while the mutations providing constitutive oncogenic signaling in the remaining melanomas are not known. We established a melanoma cell line from a tumor with none of the common driver mutations. This cell line demonstrated a signaling profile similar to BRAF-mutants, but lacked sensitivity to the BRAF inhibitor vemurafenib. RNA-seq mutation data implicated CRAF R391W as the alternative driver mutation of this melanoma. CRAF R391W was homozygous and over expressed. These melanoma cells were highly sensitive to CRAF, but not BRAF knockdown. In reconstitution experiments, CRAF R391W, but not CRAF WT, transformed NIH3T3 cells in soft-agar colony formation assays, increased kinase activity in vitro, induced MAP kinase signaling and conferred vemurafenib resistance. MAP kinase inducing activity was dependent on CRAF dimerization. Thus, CRAF is a bona fide alternative oncogene for BRAF/NRAS/GNAQ/GNA11 wild type melanomas. PMID- 27273453 TI - Mechanical properties of the superficial biofilm layer determine the architecture of biofilms. AB - Cells in biofilms sense and interact with their environment through the extracellular matrix. The physicochemical properties of the matrix, particularly at the biofilm-environment interface, determine how cells respond to changing conditions. In this study we describe the application of atomic force microscopy and confocal imaging to probe in situ the mechanical properties of these interfacial regions and to elucidate how key matrix components can contribute to the physical sensing by the cells. We describe how the Young's modulus of microcolonies differs according to the size and morphology of microcolonies, as well as the flow rate. The Young's modulus increased as a function of microcolony diameter, which was correlated with the production of the polysaccharide Psl at later stages of maturation for hemispherical or mushroom shaped microcolonies. The Young's modulus of the periphery of the biofilm colony was however independent of the hydrodynamic shear. The morphology of the microcolonies also influenced interfacial or peripheral stiffness. Microcolonies with a diffuse morphology had a lower Young's modulus than isolated, circular ones and this phenomenon was due to a deficiency of Psl. In this way, changes in the specific polysaccharide components imbue the biofilm with distinct physical properties that may modulate the way in which bacteria perceive or respond to their environment. Further, the physical properties of the polysaccharides are closely linked to the specific architectures formed by the developing biofilm. PMID- 27273454 TI - High-Performance of Gas Hydrates in Confined Nanospace for Reversible CH4 /CO2 Storage. AB - The molecular exchange of CH4 for CO2 in gas hydrates grown in confined nanospace has been evaluated for the first time using activated carbons as a host structure. The nano-confinement effects taking place inside the carbon cavities and the exceptional physicochemical properties of the carbon structure allows us to accelerate the formation and decomposition process of the gas hydrates from the conventional timescale of hours/days in artificial bulk systems to minutes in confined nanospace. The CH4 /CO2 exchange process is fully reversible with high efficiency at practical temperature and pressure conditions. Furthermore, these activated carbons can be envisaged as promising materials for long-distance natural gas and CO2 transportation because of the combination of a high storage capacity, a high reversibility, and most important, with extremely fast kinetics for gas hydrate formation and release. PMID- 27273456 TI - Mononuclear Nonheme High-Spin (S=2) versus Intermediate-Spin (S=1) Iron(IV)-Oxo Complexes in Oxidation Reactions. AB - Mononuclear nonheme high-spin (S=2) iron(IV)-oxo species have been identified as the key intermediates responsible for the C-H bond activation of organic substrates in nonheme iron enzymatic reactions. Herein we report that the C-H bond activation of hydrocarbons by a synthetic mononuclear nonheme high-spin (S=2) iron(IV)-oxo complex occurs through an oxygen non-rebound mechanism, as previously demonstrated in the C-H bond activation by nonheme intermediate (S=1) iron(IV)-oxo complexes. We also report that C-H bond activation is preferred over C=C epoxidation in the oxidation of cyclohexene by the nonheme high-spin (HS) and intermediate-spin (IS) iron(IV)-oxo complexes, whereas the C=C double bond epoxidation becomes a preferred pathway in the oxidation of deuterated cyclohexene by the nonheme HS and IS iron(IV)-oxo complexes. In the epoxidation of styrene derivatives, the HS and IS iron(IV) oxo complexes are found to have similar electrophilic characters. PMID- 27273455 TI - Concordance of haemoglobin A1c, blood pressure and C-reactive protein between children and their parents in Chinese households. AB - BACKGROUND: China has the world's highest diabetes prevalence, which along with hypertension and inflammation continues to grow particularly among children. Little is known about the strength of the association of these cardiometabolic risk factors between parents and their children; thus, the potential of household based strategies to reduce risk is unknown. OBJECTIVES: The objective of the study is to examine the parent-child association for haemoglobin A1c (HbA1c), blood pressure (BP) and C-reactive protein (CRP) in a large, geographically diverse Chinese sample. METHODS: In 940 parent-child pairs (children aged 7-17 years) who participated in the 2009 China Health and Nutrition Survey, we measured each individual's HbA1c and CRP using fasting blood and BP. We used sex specific random-effects linear regression to examine the parent-child association for these risk factors, accounting for within-family clustering. RESULTS: Child's HbA1c was positively associated with parental HbA1c. Beta coefficients ranged from 0.06 (95% CI 0.03-0.12) for father-daughter to 0.43 (95% CI 0.28-0.58) for mother-son pairs. We also detected a positive mother-daughter association for BP and positive father-child associations for CRP. CONCLUSION: The statistically significant parent-child association for HbA1c, BP and CRP in Chinese families suggests that household-based interventions could be useful for confronting the high rates of diabetes, hypertension and inflammation in China. PMID- 27273457 TI - Nickel-Catalyzed Cross-Electrophile Coupling with Organic Reductants in Non-Amide Solvents. AB - Cross-electrophile coupling of aryl halides with alkyl halides has thus far been primarily conducted with stoichiometric metallic reductants in amide solvents. This report demonstrates that the use of tetrakis(dimethylamino)ethylene (TDAE) as an organic reductant enables the use of non-amide solvents, such as acetonitrile or propylene oxide, for the coupling of benzyl chlorides and alkyl iodides with aryl halides. Furthermore, these conditions work for several electron-poor heterocycles that are easily reduced by manganese. Finally, we demonstrate that TDAE addition can be used as a control element to 'hold' a reaction without diminishing yield or catalyst activity. PMID- 27273458 TI - The importance of polarizability: comparison of models of carbon disulphide in the ionic liquids [C1C1im][NTf2] and [C4C1im][NTf2]. AB - The local environment of CS2 and in solution in two ionic liquids ([C1C1im][NTf2] and [C4C1im][NTf2]) are investigated by atomistic simulation and compared with that in neat CS2. The intermolecular vibrational densities of states of CS2 are calculated and compared with experimental OHD-RIKES spectra. The fair agreement of the results from solutions but poor agreement of the results from neat CS2 suggest that while collective effects are unimportant in solutions, they have a major effect on the OHD-RIKES spectrum of neat CS2. Comparing polarizable and unpolarizable models for CS2 emphasizes the importance of polarizability in determining local structure. PMID- 27273459 TI - Trauma-Related Guilt Mediates the Relationship between Posttraumatic Stress Disorder and Suicidal Ideation in OEF/OIF/OND Veterans. AB - Posttraumatic stress disorder (PTSD) and trauma-related guilt are risk factors for suicidal ideation (SI) in veterans. Components of trauma-related guilt were examined as serial mediators of the relationship between PTSD and SI. In a sample of 53 OEF/OIF/OND combat veterans, PTSD had an indirect effect on SI through a serial mediation chain of guilt cognitions, distress, and global guilt, suggesting that trauma-related guilt via cognitions, distress, and global guilt is a pathway from PTSD to SI. Attention should be given to assessing and addressing trauma-related guilt in veterans experiencing PTSD to prevent SI. PMID- 27273460 TI - Assessment of Heterotrophic Growth Supported by Soluble Microbial Products in Anammox Biofilm using Multidimensional Modeling. AB - Anaerobic ammonium oxidation (anammox) is known to autotrophically convert ammonium to dinitrogen gas with nitrite as the electron acceptor, but little is known about their released microbial products and how these are relative to heterotrophic growth in anammox system. In this work, we applied a mathematical model to assess the heterotrophic growth supported by three key microbial products produced by bacteria in anammox biofilm (utilization associated products (UAP), biomass associated products (BAP), and decay released substrate). Both One dimensional and two-dimensional numerical biofilm models were developed to describe the development of anammox biofilm as a function of the multiple bacteria-substrate interactions. Model simulations show that UAP of anammox is the main organic carbon source for heterotrophs. Heterotrophs are mainly dominant at the surface of the anammox biofilm with small fraction inside the biofilm. 1-D model is sufficient to describe the main substrate concentrations/fluxes within the anammox biofilm, while the 2-D model can give a more detailed biomass distribution. The heterotrophic growth on UAP is mainly present at the outside of anammox biofilm, their growth on BAP (HetB) are present throughout the biofilm, while the growth on decay released substrate (HetD) is mainly located in the inner layers of the biofilm. PMID- 27273461 TI - Pharmacokinetic Evaluation of CYP3A4-Mediated Drug-Drug Interactions of Isavuconazole With Rifampin, Ketoconazole, Midazolam, and Ethinyl Estradiol/Norethindrone in Healthy Adults. AB - This report describes the phase 1 trials that evaluated the metabolism of the novel triazole antifungal isavuconazole by cytochrome P450 3A4 (CYP3A4) and isavuconazole's effects on CYP3A4-mediated metabolism in healthy adults. Coadministration of oral isavuconazole (100 mg once daily) with oral rifampin (600 mg once daily; CYP3A4 inducer) decreased isavuconazole area under the concentration-time curve (AUCtau ) during a dosing interval by 90% and maximum concentration (Cmax ) by 75%. Conversely, coadministration of isavuconazole (200 mg single dose) with oral ketoconazole (200 mg twice daily; CYP3A4 inhibitor) increased isavuconazole AUC from time 0 to infinity (AUC0-infinity ) and Cmax by 422% and 9%, respectively. Isavuconazole was coadministered (200 mg 3 times daily for 2 days, then 200 mg once daily) with single doses of oral midazolam (3 mg; CYP3A4 substrate) or ethinyl estradiol/norethindrone (35 MUg/1 mg; CYP3A4 substrate). Following coadministration, AUC0-infinity increased 103% for midazolam, 8% for ethinyl estradiol, and 16% for norethindrone; Cmax increased by 72%, 14%, and 6%, respectively. Most adverse events were mild to moderate in intensity; there were no deaths, and serious adverse events and adverse events leading to study discontinuation were rare. These results indicate that isavuconazole is a sensitive substrate and moderate inhibitor of CYP3A4. PMID- 27273462 TI - Effects Of treadmill training on hindlimb muscles of spinal cord-injured mice. AB - INTRODUCTION: Treadmill training is known to prevent muscle atrophy after spinal cord injury (SCI), but the training duration required to optimize recovery has not been investigated. METHODS: Hemisected mice were randomized to 3, 6, or 9 weeks of training or no training. Muscle fiber type composition and fiber cross sectional area (CSA) of medial gastrocnemius (MG), soleus (SOL), and tibialis anterior (TA) were assessed using ATPase histochemistry. RESULTS: Muscle fiber type composition of SCI animals did not change with training. However, 9 weeks of training increased the CSA of type IIB and IIX fibers in TA and MG muscles. CONCLUSIONS: Nine weeks of training after incomplete SCI was effective in preventing atrophy of fast-twitch muscles, but there were limited effects on slow twitch muscles and muscle fiber type composition. These data provide important evidence of the benefits of exercising paralyzed limbs after SCI. Muscle Nerve, 2016 Muscle Nerve 55: 232-242, 2017. PMID- 27273463 TI - Incidence and risk factors of bacterial infections in children following autologous hematopoietic stem cell transplantation: Single-center experience from Jordan. AB - Bacterial infection is a serious sequela following AHSCT; however, limited data are available regarding pediatric recipients, especially in developing countries. We retrospectively analyzed the incidence and risk factors of bacterial infections during the first 100 days after AHSCT in children at KHCC in Amman, Jordan between January, 2005 and September, 2013. A total of 65 patients were identified, with median age of four yr (1-17). Forty-seven patients (72.3%) had solid tumors and 18 (27.7%) had lymphoma. Bacterial infections were documented in 33 patients (50%), with a total of 63 episodes. Gram-negative infection (57.1%) was more prevalent than Gram-positive infection (38%). The risk of bacterial infections was higher among patients less than five yr of age (p = 0.028) and those who developed hypogammaglobulinemia requiring IVIG replacement (p = 0.001). Patients with solid tumors developed more bacterial infections compared to patients with lymphoma (p = 0.0057). No deaths were attributed to bacterial infection. Bacterial infection rate is high among recipients of AHSCT in Jordan with Gram-negative bacteria being the most common. PMID- 27273465 TI - Reducible Dimeric Conjugates of Small Internally Segment Interfering RNA for Efficient Gene Silencing. AB - The condensation of nucleic acids into compact nanoparticles with cationic carriers is a powerful tool for translocating exogenous nucleic acids into cells. To date, most efforts have been focused on the development of novel gene carriers for safe and efficient gene delivery. However, small interfering RNA (siRNA) is generally not strongly associated with cationic carriers due to its stiff structure and low spatial charge density. To overcome this limitation, this work introduces a well-defined dimeric conjugate of small internally segment interfering RNA (sisiRNA) linked via a disulfide bond for enhanced cellular uptake and gene silencing. Dimeric sisiRNA is synthesized through oxidizing two monomeric sisiRNA molecules, each of which consists of a sense strand carrying a nick and an antisense strand modified with a thiol group at the 3'-end. The nick in the sense strand enables the dimeric sisiRNA to be more effectively condensed into nanosized complexes due to the increased structural flexibility, which results in a higher gene silencing efficiency compared with the dimeric siRNA containing the intact sense strands. The results indicate that the discontinuity of the sense strands is a simple method of adding more flexibility to various siRNA-based nanostructures for enhanced gene silencing. PMID- 27273466 TI - A Green Approach to High-Performance Supercapacitor Electrodes: The Chemical Activation of Hydrochar with Potassium Bicarbonate. AB - Sustainable synthesis schemes for the production of porous carbons with appropriate textural properties for use as supercapacitor electrodes are in high demand. In this work a greener option to the widely used but corrosive KOH is proposed for the production of highly porous carbons. Hydrochar products are used as carbon precursors. It is demonstrated that a mild alkaline potassium salt such as potassium bicarbonate is very effective to generate porosity in hydrochar to lead to materials with large surface areas (> 2000 m(2) g(-1) ) and a tunable pore size distribution. Furthermore, the use of KHCO3 instead of KOH gives rise to a significant 10 % increase in the yield of activated carbon, and the spherical morphology of hydrochar is retained, which translates into better packing properties and reduced ion diffusion distances. These features lead to a supercapacitor performance that can compete with, and even surpass, that of KOH activated hydrochar in a variety of electrolytes. PMID- 27273464 TI - Slitrk1 is localized to excitatory synapses and promotes their development. AB - Following the migration of the axonal growth cone to its target area, the initial axo-dendritic contact needs to be transformed into a functional synapse. This multi-step process relies on overlapping but distinct combinations of molecules that confer synaptic identity. Slitrk molecules are transmembrane proteins that are highly expressed in the central nervous system. We found that two members of the Slitrk family, Slitrk1 and Slitrk2, can regulate synapse formation between hippocampal neurons. Slitrk1 is enriched in postsynaptic fractions and is localized to excitatory synapses. Overexpression of Slitrk1 and Slitrk2 in hippocampal neurons increased the number of synaptic contacts on these neurons. Furthermore, decreased expression of Slitrk1 in hippocampal neurons led to a reduction in the number of excitatory, but not inhibitory, synapses formed in hippocampal neuron cultures. In addition, we demonstrate that different leucine rich repeat domains of the extracellular region of Slitrk1 are necessary to mediate interactions with Slitrk binding partners of the LAR receptor protein tyrosine phosphatase family, and to promote dimerization of Slitrk1. Altogether, our results demonstrate that Slitrk family proteins regulate synapse formation. PMID- 27273467 TI - Adjuvant Therapy for Colon Cancer: Small Steps Toward Precision Medicine. PMID- 27273468 TI - Dental implants in the elderly population: a systematic review and meta-analysis. AB - OBJECTIVE: This systematic review was conducted to evaluate the outcome of dental implant therapy in elderly patients (>=65 years). MATERIAL AND METHODS: Online database and hand searches were systematically performed to identify studies reporting on dental implants placed in the partially/completely edentulous jaws of elderly patients. Only prospective studies reporting on regular-diameter (>=3 mm), micro-rough surface implants were included in this review. Two investigators performed the search and data extraction. An inter-investigator reliability was verified using kappa statistics (kappa). A meta-analysis was performed on implant survival rates, while the mean peri-implant marginal bone level changes (PI-MBL), technical/mechanical complications, and biological complications were reported descriptively. RESULTS: The systematic search yielded 2221 publications, of which 11 studies were included for statistical analyses. The calculated kappa for the various parameters extracted was kappa = 0.818-1.000. A meta-analysis was performed on the post-loading implant survival rates at 1, 3, 5, and 10 years. The random-effects model revealed an overall 1-year implant survival of 97.7% (95% CI: 95.8, 98.8; I2 = 0.00%, P = 0.968; n = 11 studies). The model further revealed an overall implant survival of 96.3% (95% CI: 92.8, 98.1; I2 = 0.00%, P = 0.618; n = 6 studies), 96.2% (95% CI: 93.0, 97.9; I2 = 0.00%, P = 0.850; n = 7 studies), and 91.2% (95% CI: 83.4, 95.6; I2 = 0.00%, P = 0.381; n = 3 studies) for 3, 5, and 10 years, respectively. The reported 1-year average PI-MBL ranged between 0.1 and 0.3 mm, while the reported 5- and 10-year PI-MBL were 0.7 and 1.5 mm, respectively. Information obtained pertaining to the technical and biological complications in the included studies was inadequate for statistical analysis. The frequent technical/mechanical complications reported were abutment screw loosening, fracture of the overdenture prostheses, activation of retentive clips, ceramic chipping, and fractures. The common biological complication reported included peri-implant mucositis, mucosal enlargement, bone loss, pain, and implant loss. CONCLUSIONS: This review provides robust evidence favoring dental implant therapy in elderly patients as a predictable long-term treatment option, in terms of implant survival, clinically acceptable PI-MBL changes, and minimal complications. Therefore, age alone should not be a limiting factor for dental implant therapy. PMID- 27273469 TI - Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia. AB - Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids. PMID- 27273471 TI - Practicing the art of medicine in the era of technology. PMID- 27273472 TI - Infantile haemangiomas do not occur more frequently in children with congenital melanocytic naevi. PMID- 27273470 TI - Transducer-based evaluation of tremor. AB - The International Parkinson and Movement Disorder Society established a task force on tremor that reviewed the use of transducer-based measures in the quantification and characterization of tremor. Studies of accelerometry, electromyography, activity monitoring, gyroscopy, digitizing tablet-based measures, vocal acoustic analysis, and several other transducer-based methods were identified by searching PubMed.gov. The availability, use, acceptability, reliability, validity, and responsiveness were reviewed for each measure using the following criteria: (1) used in the assessment of tremor; (2) used in published studies by people other than the developers; and (3) adequate clinimetric testing. Accelerometry, gyroscopy, electromyography, and digitizing tablet-based measures fulfilled all three criteria. Compared to rating scales, transducers are far more sensitive to changes in tremor amplitude and frequency, but they do not appear to be more capable of detecting a change that exceeds random variability in tremor amplitude (minimum detectable change). The use of transducer-based measures requires careful attention to their limitations and validity in a particular clinical or research setting. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27273473 TI - Experiments with Seasonal Forecasts of ocean conditions for the Northern region of the California Current upwelling system. AB - Resource managers at the state, federal, and tribal levels make decisions on a weekly to quarterly basis, and fishers operate on a similar timeframe. To determine the potential of a support tool for these efforts, a seasonal forecast system is experimented with here. JISAO's Seasonal Coastal Ocean Prediction of the Ecosystem (J-SCOPE) features dynamical downscaling of regional ocean conditions in Washington and Oregon waters using a combination of a high resolution regional model with biogeochemistry and forecasts from NOAA's Climate Forecast System (CFS). Model performance and predictability were examined for sea surface temperature (SST), bottom temperature, bottom oxygen, pH, and aragonite saturation state through model hindcasts, reforecast, and forecast comparisons with observations. Results indicate J-SCOPE forecasts have measurable skill on seasonal timescales. Experiments suggest that seasonal forecasting of ocean conditions important for fisheries is possible with the right combination of components. Those components include regional predictability on seasonal timescales of the physical environment from a large-scale model, a high resolution regional model with biogeochemistry that simulates seasonal conditions in hindcasts, a relationship with local stakeholders, and a real-time observational network. Multiple efforts and approaches in different regions would advance knowledge to provide additional tools to fishers and other stakeholders. PMID- 27273475 TI - Middle East respiratory syndrome-related knowledge, preventive behaviours and risk perception among nursing students during outbreak. AB - AIMS AND OBJECTIVES: The aim of this study was to survey nursing students' Middle East respiratory syndrome-related knowledge, preventive behaviours and risk perception to examine the correlations among the variables during a Middle East respiratory syndrome outbreak. BACKGROUND: Middle East respiratory syndrome is a new viral respiratory illness. Nursing students who engage in clinical practice at hospitals may have been exposed to Middle East respiratory syndrome infection during the Middle East respiratory syndrome outbreak. DESIGN: This study was a descriptive cross-sectional survey. METHODS: Participants (n = 249) were nursing students in their third or fourth year of the programme who were engaged in clinical practice for eight hours per day at the tertiary hospitals with Middle East respiratory syndrome patients. Knowledge, preventive behaviours and risk perception related to Middle East respiratory syndrome were measured using scales developed through a preliminary survey and validity testing. RESULTS: The subjects' knowledge level of Middle East respiratory syndrome was 84.4%; their practice of preventive behaviours was rated at 44.5%; and their risk perception rating was 2.4 out of 5. Middle East respiratory syndrome-related risk perception was significantly different according to gender and Middle East respiratory syndrome education. Middle East respiratory syndrome-related knowledge was significantly correlated with preventive behaviours and risk perception. CONCLUSION: Considering the low scores for items regarding knowledge and preventive behaviours, it is necessary to develop effective and systematic publicity and education programmes for nursing students. Enhancing Middle East respiratory syndrome-related knowledge by considering cooperation between hospitals and universities will sharpen nursing students' risk perception of the disease and effectively increase their preventive behaviours. RELEVANCE TO CLINICAL PRACTICE: Similar to other emerging infectious diseases, Middle East respiratory syndrome outbreaks may occur in other countries. The results of this study can be used to develop and apply efficient and feasible Middle East respiratory syndrome education programmes for nursing students during Middle East respiratory syndrome outbreaks. PMID- 27273474 TI - Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study. AB - Anorexia nervosa (AN) is a debilitating illness and existing interventions are only modestly effective. This study aimed to determine whether AN pathophysiology is associated with altered connections within fronto-accumbal circuitry subserving reward processing. Diffusion and resting-state functional MRI scans were collected in female inpatients with AN (n = 22) and healthy controls (HC; n = 18) between the ages of 16 and 25 years. Individuals with AN were scanned during the acute, underweight phase of the illness and again following inpatient weight restoration. HC were scanned twice over the same timeframe. Based on univariate and multivariate analyses of fronto-accumbal circuitry, underweight individuals with AN were found to have increased structural connectivity (diffusion probabilistic tractography), increased white matter anisotropy (tract based spatial statistics), increased functional connectivity (seed-based correlation in resting-state fMRI), and altered effective connectivity (spectral dynamic causal modeling). Following weight restoration, fronto-accumbal structural connectivity continued to be abnormally increased bilaterally with large (partial eta2 = 0.387; right NAcc-OFC) and moderate (partial eta2 = 0.197; left NAcc-OFC) effect sizes. Increased structural connectivity within fronto-accumbal circuitry in the underweight state correlated with severity of eating disorder symptoms. Taken together, the findings from this longitudinal, multimodal neuroimaging study offer converging evidence of atypical fronto accumbal circuitry in AN. Hum Brain Mapp 37:3835-3846, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273477 TI - Towards the Better: Intrinsic Property Amelioration in Bulk Metallic Glasses. AB - Tailoring the intrinsic length-scale effects in bulk metallic glasses (BMGs) via post-heat treatment necessitates a systematic analyzing strategy. Although various achievements were made in the past years to structurally enhance the properties of different BMG alloys, the influence of short-term sub-glass transition annealing on the relaxation kinetics is still not fully covered. Here, we aim for unraveling the connection between the physical, (thermo)mechanical and structural changes as a function of selected pre-annealing temperatures and time scales with an in-house developed Cu46Zr44Al8Hf2 based BMG alloy. The controlled formation of nanocrystals below 50 nm with homogenous distribution inside the matrix phase via thermal treatment increase the material's resistance to strain softening by almost an order of magnitude. The present work determines the design aspects of metallic glasses with enhanced mechanical properties via nanostructural modifications, while postulating a counter-argument to the intrinsic property degradation accounted for long-term annealing. PMID- 27273476 TI - Structural flexibility of the periplasmic protein, FlgA, regulates flagellar P ring assembly in Salmonella enterica. AB - A periplasmic flagellar chaperone protein, FlgA, is required for P-ring assembly in bacterial flagella of taxa such as Salmonella enterica or Escherichia coli. The mechanism of chaperone-mediated P-ring formation is poorly understood. Here we present the open and closed crystal structures of FlgA from Salmonella enterica serovar Typhimurium, grown under different crystallization conditions. An intramolecular disulfide cross-linked form of FlgA caused a dominant negative effect on motility of the wild-type strain. Pull-down experiments support a specific protein-protein interaction between FlgI, the P-ring component protein, and the C-terminal domain of FlgA. Surface plasmon resonance and limited proteolysis indicate that flexibility of the domain is reduced in the covalently closed form. These results show that the structural flexibility of the C-terminal domain of FlgA, which is related to the structural difference between the two crystal forms, is intrinsically associated with its molecular chaperone function in P-ring assembly. PMID- 27273478 TI - Association between Helicobacter pylori infection and metabolic syndrome: a systematic review and meta-analysis. AB - OBJECTIVE: To systematically review and quantify the effect of Helicobacter pylori (H. pylori) infection on the risk of metabolic syndrome (MS) and metabolic parameters in individuals with H. pylori infection. METHODS: A systematic search of MEDLINE and EMBASE was performed. Inclusion criteria were observational studies assessing the association between H. pylori infection and MS in adult participants. We calculated the pooled effect estimate of MS with 95% confidence interval (CI) between patients infected with H. pylori and those without by using a random-effects model. The secondary outcomes were the differences between groups in homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), body mass index (BMI) and systolic blood pressure (SBP). RESULTS: Altogether 18 trials with 27 544 participants met the inclusion criteria. Six trials were included in the analysis of MS. There was a statistically significant association between H. pylori and MS with a pooled odds ratio of 1.34 (95% CI 1.17-1.53, I(2) = 39%, Pheterogeneity < 0.01). Between the infected and non infected groups there were significant differences in FBG, HDL-C, BMI, triglyceride, HOMA-IR and SBP (all P < 0.05). CONCLUSION: H. pylori infection is positively associated with MS. Infection with H. pylori is also associated with higher triglyceride, FBG, BMI, HOMA-IR, SBP and lower HDL-C. PMID- 27273480 TI - Yap/Taz transcriptional activity in endothelial cells promotes intramembranous ossification via the BMP pathway. AB - Osteogenesis is categorized into two groups based on developmental histology, intramembranous and endochondral ossification. The role of blood vessels during endochondral ossification is well known, while their role in intramembranous ossification, especially the intertissue pathway, is poorly understood. Here, we demonstrate endothelial Yap/Taz is a novel regulator of intramembranous ossification in zebrafish. Appropriate blood flow is required for Yap/Taz transcriptional activation in endothelial cells and intramembranous ossification. Additionally, Yap/Taz transcriptional activity in endothelial cells specifically promotes intramembranous ossification. BMP expression by Yap/Taz transactivation in endothelial cells is also identified as a bridging factor between blood vessels and intramembranous ossification. Furthermore, the expression of Runx2 in pre-osteoblast cells is a downstream target of Yap/Taz transcriptional activity in endothelial cells. Our results provide novel insight into the relationship between blood flow and ossification by demonstrating intertissue regulation. PMID- 27273481 TI - Tolerability of Japanese Encephalitis Vaccine in Pediatric Patients. AB - Background.: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus endemic to parts of Asia. Manufacture of JE-VAX, the mouse brain-derived vaccine against JEV, was discontinued in February 2011. IXIARO, an inactivated cell culture-derived vaccine, was approved in 2009 for use in adult patients. Although IXIARO was not licensed for pediatric patients until 2013, our clinic routinely used this vaccine in at-risk children starting in 2011. The purpose of this study was to review our experience as to the tolerability of the new IXIARO vaccine in children. Methods.: We performed a retrospective chart review of all patients less than 18 years of age who received at least 1 dose of IXIARO in our Family Travel Clinic from November 2011 through August 2014. Subjects' electronic medical records were reviewed for any documented medical visits within 3 months after vaccination. Each visit was assessed for possible adverse events with relationship to vaccine administration as determined by the reviewer. Results.: Ninety-two patients less than 18 years of age received a total of 145 doses of IXIARO between November 2011 and August 2014. Seven adverse events were documented. Only 1 was deemed to be possibly related. No serious adverse events were found on chart review. Conclusions.: Our study reinforces the recent decision to expand IXIARO vaccination to the pediatric population. The experience in our clinic since vaccine introduction shows it to be overall tolerable when used in routine clinical practice. Practitioners should feel comfortable recommending vaccination against JEV for any pediatric traveler to an area of risk. PMID- 27273485 TI - In Defense of Off-label Prescribing. PMID- 27273479 TI - Urinary excretions of 34 dietary polyphenols and their associations with lifestyle factors in the EPIC cohort study. AB - Urinary excretion of 34 dietary polyphenols and their variations according to diet and other lifestyle factors were measured by tandem mass spectrometry in 475 adult participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study. A single 24-hour urine sample was analysed for each subject from 4 European countries. The highest median levels were observed for phenolic acids such as 4-hydroxyphenylacetic acid (157 MUmol/24 h), followed by 3-hydroxyphenylacetic, ferulic, vanillic and homovanillic acids (20-50 MUmol/24 h). The lowest concentrations were observed for equol, apigenin and resveratrol (<0.1 MUmol/24 h). Urinary polyphenols significantly varied by centre, followed by alcohol intake, sex, educational level, and energy intake. This variability is largely explained by geographical variations in the diet, as suggested by the high correlations (r > 0.5) observed between urinary polyphenols and the intake of their main food sources (e.g., resveratrol and gallic acid ethyl ester with red wine intake; caffeic, protocatechuic and ferulic acids with coffee consumption; and hesperetin and naringenin with citrus fruit intake). The large variations in urinary polyphenols observed are largely determined by food preferences. These polyphenol biomarkers should allow more accurate evaluation of the relationships between polyphenol exposure and the risk of chronic diseases in large epidemiological studies. PMID- 27273486 TI - In Defense of Off-label Prescribing-Reply. PMID- 27273487 TI - Hypertension, the Swedish Patient Register, and Selection Bias. PMID- 27273488 TI - Questioning Nicotine Replacement Therapy Without Behavioral Support. PMID- 27273489 TI - Hypertension, the Swedish Patient Register, and Selection Bias-Reply. PMID- 27273490 TI - Questioning Nicotine Replacement Therapy Without Behavioral Support-Reply. PMID- 27273491 TI - Estimating Vitamin D Status and the Choice of Supplementation Dose. PMID- 27273492 TI - Estimating Vitamin D Status and the Choice of Supplementation Dose-Reply. PMID- 27273493 TI - Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease. PMID- 27273494 TI - Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease. PMID- 27273495 TI - Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease. PMID- 27273496 TI - Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease. PMID- 27273497 TI - Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease. PMID- 27273498 TI - Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease. PMID- 27273499 TI - Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease-Reply. PMID- 27273500 TI - Imaging More Wisely-Already At Work. PMID- 27273501 TI - Imaging More Wisely-Already At Work-Reply. PMID- 27273503 TI - Brain Herniation into Arachnoid Granulations: Clinical and Neuroimaging Features. AB - BACKGROUND/PURPOSE: Brain herniation into presumed arachnoid granulations (BHAG) is an increasingly recognized entity. Though it has previously been described as isointense to brain matter on magnetic resonance imaging (MRI), we have encountered 21 cases in our clinical practice, many of which have signal abnormality in the herniated or adjacent parenchyma. We performed a systematic analysis on these cases to further understand the clinical significance. METHODS: This is a retrospective analysis of cases collected from our clinical MRI practice. Each case was evaluated for location, size, lobe of origin, associated signal abnormality, symptoms, and the presence or absence of intracranial hypertension. RESULTS: Twenty-one cases of BHAG identified in 16 patients. Seven cases (7/21, 33%) demonstrated signal abnormality in the herniated or underlying parenchyma. On serial imaging, the size of herniation either fluctuated (2/10, 20%) or stayed the same (8/10, 80%). The associated signal abnormalities increased (1/5, 20%), decreased (1/5, 20%), or remained stable (3/5, 60%). Four patients (4/16, 25%) had signs/symptoms that could be associated with the BHAG. Ten patients (10/16, 63%) had either imaging findings or clinical signs that could be associated with intracranial hypertension. CONCLUSION: In contrast to previously reported cases, our study demonstrates that BHAG can be associated with MRI signal abnormalities of the herniated and adjacent brain. Symptoms are typically absent, though may be present in a small subset of patients, regardless of the presence of signal change or encephalomalacia of the involved brain. Indirect evidence of intracranial hypertension is present in a majority of patients but completely lacking in others. PMID- 27273502 TI - Human mesenchymal stem cells attenuate pulmonary hypertension induced by prenatal lipopolysaccharide treatment in rats. AB - Intra-amniotic injection of lipopolysaccharide (LPS) induces pulmonary hypertension in newborn rats. This study was designed to test whether human mesenchymal stem cells (MSCs) reduce pulmonary hypertension and alleviate cardiac hypertrophy in prenatal LPS-treated rats. Pregnant Sprague-Dawley rats were injected intraperitoneally with LPS (0.5 mg/kg per day) or untreated on gestational days 20 and 21. Human MSCs (3*10(5) cells and 1*10(6) cells) in 0.03 mL of normal saline (NS) were transplanted intratracheally on postnatal day 5. Four study groups were considered: normal, LPS+NS, LPS+MSCs (3*10(5) cells), and LPS+MSCs (1*10(6) cells). On postnatal day 14, lung and heart tissues were collected for measuring the arterial medial wall thickness (MWT) and beta-myosin heavy chain (beta-MHC) level as markers of pulmonary hypertension and cardiac hypertrophy, respectively. The LPS+NS group exhibited a significantly higher right ventricle (RV)/[left ventricle (LV)+ interventricular septum (IVS)] thickness ratio and MWT, a greater cardiomyocyte width, a greater number of cardiomyocyte nuclei per squared millimeter, and higher beta-MHC expression than those observed in the normal group. Human MSC transplantation (3*10(5) cells and 1*10(6) cells) in LPS-treated rats reduced MWT and the RV/(LV+IVS) thickness ratio to normal levels. This improvement in right ventricular hypertrophy was accompanied by a decrease in toll-like receptor 4 (TLR4), nuclear factor-kappaB, and tumor necrosis factor-alpha expression in the heart. Intratracheal human MSCs transplantation can attenuate pulmonary hypertension and right ventricular hypertrophy in prenatal LPS-treated rats; this attenuation may be associated with suppression of TLR4 expression via paracrine pathways. PMID- 27273504 TI - I. QUALITY THRESHOLDS, FEATURES, AND DOSAGE IN EARLY CARE AND EDUCATION: INTRODUCTION AND LITERATURE REVIEW. AB - This monograph addresses the hypotheses that preschool children benefit most strongly when early care and education (ECE) is at or above a threshold of quality, has specific quality features, and/or is of longer duration. These issues are pivotal in recent policies designed to improve the quality of ECE, especially for children from low-income families. Evidence of quality thresholds in which ECE quality has stronger impacts in settings with moderate to high levels of quality than in settings with low quality would inform policy initiatives in which monetary incentives or consequences are allocated to ECE settings based on their level of quality. Evidence that specific features of quality, such as quality of teacher-child interactions and of literacy and mathematics instruction, are predictors of gains in child outcomes could help inform quality improvement efforts. Evidence that more time spent in center-based ECE or in instruction in specific content areas predict larger gains among preschoolers could be useful in designing public preschool programs such as Head Start or prekindergarten. Secondary data analyses of eight large studies of preschool children in center-based ECE were conducted. Analyses focused on quality thresholds and quality features examined the extent to which three types of quality measures predicted gains in children's language, literacy, mathematics, and social skills. The measures comprised (1) global quality measures that provide an overall or global rating of quality, focusing on interactions as well as on physical features of the environment, activities, and routines; (2) interaction-specific measures that focus in depth on the quality of interactions between teachers and children with respect to instructional and emotional support; and (3) domain-specific measures that focus on the quality of instruction and stimulation in specific content areas such as early language and literacy. The goal was to provide replicated analyses with data from several projects in order to address each question. Multilevel analyses that controlled for entry skills were conducted, and results were combined by using meta analysis, nonlinear and nonparametric analyses, and propensity score analyses. With respect to thresholds, the analyses suggest that increases in the quality of instruction are related to larger gains in language and literacy outcomes, but only in higher quality classrooms. Results point to stronger associations between quality and child outcomes in higher versus lower quality classrooms for measures of the instructional quality of teacher-child interactions and of the quality of specific activities thought to promote early literacy, such as teaching phonemic skills and book reading. In addition, the items focusing on quality of interactions on the global measure also predicted acquisition of language and social skills in higher but not in lower quality classrooms. With respect to quality features, interaction-specific and especially domain-specific measures of quality remained significant predictors of child outcomes, whereas global measures of quality were never significant positive predictors, when both global and more specific measures of quality were included simultaneously in analyses. There is thus consistent evidence that more specific measures of quality are better predictors of child outcomes. With respect to dosage, several approaches were used in operationalizing both the cumulative and current dosage of children's exposure to ECE. Propensity score analyses that included baseline scores on outcomes to control for selection into larger dosages suggested that children with two as opposed to one year of Head Start had stronger vocabulary and literacy skills both immediately upon exit from Head Start and at the end of kindergarten. Fewer absences and more observed time spent on instruction were associated with stronger gains in literacy and mathematics skills. Finally, findings revealed that more time spent on instruction in classrooms with higher overall quality was particularly important to the development of mathematics skills. No other replicated evidence of quality by quantity interactions emerged. PMID- 27273505 TI - II. QUALITY THRESHOLDS, FEATURES, AND DOSAGE IN EARLY CARE AND EDUCATION: METHODS. PMID- 27273506 TI - III. TESTING FOR QUALITY THRESHOLDS AND FEATURES IN EARLY CARE AND EDUCATION. AB - In this chapter, we report on the analyses focusing on both quality thresholds and quality features. First, we address questions about quality thresholds, using two analytic approaches. The analyses ask whether there is evidence suggesting thresholds in the association between a specific quality measure and a specific child outcome. Second, we extend these analyses to ask whether each child outcome is more strongly related to global quality measures or to quality measures that measure teacher-child interactions or quality of instruction in a given content area. The research to date provides the basis for the articulation of two hypotheses related to quality thresholds and features: (1) the quality of ECE is a stronger predictor of residualized gains in child outcomes in classrooms with higher quality than in classrooms with lower quality and (2) more specific measures of quality are stronger predictors of residualized gains in child outcomes than are global measures. We turn now to analyses intended to address these hypotheses by using data from several data sets. PMID- 27273507 TI - IV. TESTING FOR DOSAGE-OUTCOME ASSOCIATIONS IN EARLY CARE AND EDUCATION. PMID- 27273508 TI - V. QUALITY THRESHOLDS, FEATURES, AND DOSAGE IN EARLY CARE AND EDUCATION: DISCUSSION AND CONCLUSIONS. PMID- 27273510 TI - REFLECTIONS ON QUALITY AND DOSAGE OF PRESCHOOL AND CHILDREN'S DEVELOPMENT. AB - This ambitious monograph tackles several important questions related to children's preschool experiences that have relevance for program and policy initiatives at the state and federal levels. The authors' approach is rigorous: they conduct parallel analyses across eight large and diverse studies of preschool children in center care and use meta-analysis to summarize patterns across studies. The study finds nonlinear associations between preschool quality and gains in language and literacy skills, with larger associations in higher versus lower quality classrooms. Results also show that domain-specific measures of preschool quality were more strongly related to children's development than global quality measures. The "dosage" of preschool was likewise important: more years in Head Start predicted larger vocabulary and literacy gains, whereas more time spent on instruction predicted greater literacy and math skills growth. In this commentary, we situate these findings in the broader literature addressing links between preschool experiences and children's development and discuss key takeaways for research, practice, and policy. PMID- 27273511 TI - Opioid agonist doses for oxycodone and morphine dependence: Findings from a retrospective case series. AB - INTRODUCTION: Use of opioid agonist treatments for prescription opioid (PO) dependence is rapidly increasing. Current guidelines are based on research with heroin users. This study aimed to examine methadone and buprenorphine dose requirements for PO-dependent people. DESIGN AND METHODS: A retrospective case series of PO-dependent patients entering methadone and buprenorphine treatment. Daily oral morphine equivalent (OME) doses at baseline were calculated using standard dose conversion calculations. Dose conversion tables were used to estimate opioid agonist doses, based on starting dose of PO. Baseline methadone and buprenorphine dose at days 7 and 28 were examined. Linear models were fit to the data. RESULTS: Participants (n = 44) were 67% male, mean age 41 years (SD 10 years); 69% reported a pain condition. The methadone group (n = 21) had a mean PO dose of 704.5 mg OME (SD 783.5 mg) prior to treatment, and mean methadone dose of 45.3 mg (SD 13.1 mg) at day 7 and 61.6 mg (SD 20.8 mg) at day 28. The buprenorphine group (n = 23) had a mean PO dose of 771.7 mg OME (SD 867.7 mg) prior to treatment, with a mean dose of 14.6 mg (SD 8.3 mg) at day 7 and 18.1 (SD 8.9 mg) at day 28. Linear relationships were not found between OME and opioid agonist dose. CONCLUSIONS: Opioid agonist dosages varied substantially between individuals, and from predicted dosages based on dose conversion tables. Use of conversion tables to guide selection of opioid agonist dosage may compromise patient safety. [Nielsen S, Bruno R, Degenhardt L, Demirkol A, Lintzeris N. Opioid agonist doses for oxycodone and morphine dependence: Findings from a retrospective case series Drug Alcohol Rev 2017;36:311-316]. PMID- 27273512 TI - Generation of an ultra-short electrical pulse with width shorter than the excitation laser. AB - We demonstrate experimentally a rare phenomenon that the width of an electrical response is shorter than that of the excitation laser. In this work, generation of an ultrashort electrical pulse is by a semi-insulating GaAs photoconductive semiconductor switch (PCSS) and the generated electrical pulse width is shorter than that of the excitation laser from diode laser. When the pulse width and energy of the excitation laser are fixed at 25.7 ns and 1.6 MUJ respectively, the width of the generated electrical pulse width by 3-mm-gap GaAs PCSS at the bias voltage of 9 kV is only 7.3 ns. The model of photon-activated charge domain (PACD) is used to explain the peculiar phenomenon in our experiment. The ultrashort electrical pulse width is mainly relevant to the time interval of PACD from occurrence to disappearance in the mode. The shorter the time interval is, the narrower the electrical pulse width will become. In more general terms, our result suggests that in nonlinear regime a response signal can have a much short width than the excitation pulses. The result clearly indicates that generating ultrashort electrical pulses can be achieved without the need of ultrashort lasers. PMID- 27273513 TI - Artificial proteins as allosteric modulators of PDZ3 and SH3 in two-domain constructs: A computational characterization of novel chimeric proteins. AB - Artificial multidomain proteins with enhanced structural and functional properties can be utilized in a broad spectrum of applications. The design of chimeric fusion proteins utilizing protein domains or one-domain miniproteins as building blocks is an important advancement for the creation of new biomolecules for biotechnology and medical applications. However, computational studies to describe in detail the dynamics and geometry properties of two-domain constructs made from structurally and functionally different proteins are lacking. Here, we tested an in silico design strategy using all-atom explicit solvent molecular dynamics simulations. The well-characterized PDZ3 and SH3 domains of human zonula occludens (ZO-1) (3TSZ), along with 5 artificial domains and 2 types of molecular linkers, were selected to construct chimeric two-domain molecules. The influence of the artificial domains on the structure and dynamics of the PDZ3 and SH3 domains was determined using a range of analyses. We conclude that the artificial domains can function as allosteric modulators of the PDZ3 and SH3 domains. Proteins 2016; 84:1358-1374. (c) 2016 Wiley Periodicals, Inc. PMID- 27273514 TI - The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression. AB - Control of mRNA levels, a fundamental aspect in the regulation of gene expression, is achieved through a balance between mRNA synthesis and decay. E26 related gene (Erg) proteins are canonical transcription factors whose previously described functions are confined to the control of mRNA synthesis. Here, we report that ERG also regulates gene expression by affecting mRNA stability and identify the molecular mechanisms underlying this function in human cells. ERG is recruited to mRNAs via interaction with the RNA-binding protein RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex. Transcriptome-wide mRNA stability analysis revealed that ERG controls the degradation of a subset of mRNAs highly connected to Aurora signaling, whose decay during S phase is necessary for mitotic progression. Our data indicate that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, integrating mRNA synthesis and degradation. PMID- 27273515 TI - Toward the atomic structure of the nuclear pore complex: when top down meets bottom up. AB - Elucidating the structure of the nuclear pore complex (NPC) is a prerequisite for understanding the molecular mechanism of nucleocytoplasmic transport. However, owing to its sheer size and flexibility, the NPC is unapproachable by classical structure determination techniques and requires a joint effort of complementary methods. Whereas bottom-up approaches rely on biochemical interaction studies and crystal-structure determination of NPC components, top-down approaches attempt to determine the structure of the intact NPC in situ. Recently, both approaches have converged, thereby bridging the resolution gap from the higher-order scaffold structure to near-atomic resolution and opening the door for structure-guided experimental interrogations of NPC function. PMID- 27273517 TI - Increased 4-hydroxy-2-nonenal-induced proteasome dysfunction is correlated with cardiac damage in streptozotocin-injected rats with isoproterenol infusion. AB - Increase in 4-hydroxy-2-nonenal (4HNE) due to oxidative stress has been observed in a variety of cardiac diseases such as diabetic cardiomyopathy. 4HNE exerts a damaging effect in the myocardium by interfering with subcellular organelles like mitochondria by forming adducts. Therefore, we hypothesized that increased 4HNE adduct formation in the heart results in proteasome inactivation in isoproterenol (ISO)-infused type 1 diabetes mellitus (DM) rats. Eight-week-old male Sprague Dawley rats were injected with streptozotocin (STZ, 65 mg kg(-1) ). The rats were infused with ISO (5 mg kg(-1) ) for 2 weeks by mini pumps, after 8 weeks of STZ injection. We studied normal control (n = 8) and DM + ISO (n = 10) groups. Cardiac performance was assessed by echocardiography and Millar catheter at the end of the protocol at 20 weeks. Initially, we found an increase in 4HNE adducts in the hearts of the DM + ISO group. There was also a decrease in myocardial proteasomal peptidase (chymotrypsin and trypsin-like) activity. Increases in cardiomyocyte area (446 +/- 32.7 vs 221 +/- 10.83) (um(2) ), per cent area of cardiac fibrosis (7.4 +/- 0.7 vs 2.7 +/- 0.5) and cardiac dysfunction were also found in DM + ISO (P < 0.05) relative to controls. We also found increased 4HNE adduct formation on proteasomal subunits. Furthermore, reduced aldehyde dehydrogenase 2 activity was observed in the myocardium of the DM + ISO group. Treatment with 4HNE (100 MUM) for 4 h on cultured H9c2 cardiomyocytes attenuated proteasome activity. Therefore, we conclude that the 4HNE-induced decrease in proteasome activity may be involved in the cardiac pathology in STZ-injected rats infused with ISO. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273518 TI - Life Satisfaction and Psychological Well-Being of Older Adults With Cancer Experience: The Role of Optimism and Volunteering. AB - Promoting health and well-being among individuals of advancing age is a significant issue due to increased incidence of cancer among older adults. This study demonstrates the benefits of expecting positive outcomes and participating in volunteer activities among older adults with cancer. We used a nationally representative sample of 2,670 individuals who have experienced cancer from the 2008 wave of the Health and Retirement Study. We constructed a structural equation model to explore the associations of optimism, volunteerism, life satisfaction, and psychological well-being. The level of optimism was a significant predictor of volunteerism, which in turn affected life satisfaction and psychological well-being. The level of engagement in volunteer activities was found to have significant path coefficients toward both life satisfaction and psychological well-being. Our study provides evidence that older adults who have experienced cancer and maintained a positive outlook on their lives and engaged in personally meaningful activities tended to experience psychological well-being and life satisfaction. PMID- 27273516 TI - Direct observation of DNA threading in flap endonuclease complexes. AB - Maintenance of genome integrity requires that branched nucleic acid molecules be accurately processed to produce double-helical DNA. Flap endonucleases are essential enzymes that trim such branched molecules generated by Okazaki-fragment synthesis during replication. Here, we report crystal structures of bacteriophage T5 flap endonuclease in complexes with intact DNA substrates and products, at resolutions of 1.9-2.2 A. They reveal single-stranded DNA threading through a hole in the enzyme, which is enclosed by an inverted V-shaped helical arch straddling the active site. Residues lining the hole induce an unusual barb-like conformation in the DNA substrate, thereby juxtaposing the scissile phosphate and essential catalytic metal ions. A series of complexes and biochemical analyses show how the substrate's single-stranded branch approaches, threads through and finally emerges on the far side of the enzyme. Our studies suggest that substrate recognition involves an unusual 'fly-casting, thread, bend and barb' mechanism. PMID- 27273519 TI - A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics. AB - Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method, LD Adjusted Regional Genetic Variance (LARGV), to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to a multiple linear regression model when no interaction or haplotype effects are present. It has several applications, such as ranking of genetic regions according to variance explained or comparison of variance explained by two or more regions. Using height and BMI data from the Health Retirement Study (N = 7,776), we show that most genetic variance lies in a small proportion of the genome and that previously identified linkage peaks have higher than expected regional variance. PMID- 27273521 TI - News Feature: The Mars anomaly. PMID- 27273523 TI - Alternative Testing Strategies for Nanomaterials: State of the Science and Considerations for Risk Analysis. AB - The rapid growth of the nanotechnology industry has warranted equal progress in the nanotoxicology and risk assessment fields. In vivo models have traditionally been used to determine human and environmental risk for chemicals; however, the use of these tests has limitations, and there are global appeals to develop reliable alternatives to animal testing. Many have investigated the use of alternative (nonanimal) testing methods and strategies have quickly developed and resulted in the generation of large toxicological data sets for numerous nanomaterials (NMs). Due to the novel physicochemical properties of NMs that are related to surface characteristics, the approach toward toxicity test development has distinct considerations from traditional chemicals, bringing new requirements for adapting these approaches for NMs. The methodical development of strategies that combine multiple alternative tests can be useful for predictive NM risk assessment and help screening-level decision making. This article provides an overview of the main developments in alternative methods and strategies for reducing uncertainty in NM risk assessment, including advantages and disadvantages of in vitro, ex vivo, and in silico methods, and examples of existing comprehensive strategies. In addition, knowledge gaps are identified toward improvements for experimental and strategy design, specifically highlighting the need to represent realistic exposure scenarios and to consider NM-specific concerns such as characterization, assay interferences, and standardization. Overall, this article aims to improve the reliability and utility of alternative testing methods and strategies for risk assessment of manufactured NMs. PMID- 27273524 TI - Validity of cluster headache diagnoses in an electronic health record data repository. AB - BACKGROUND: Cluster headache (CH) is uncommon, so electronic searches of large medical record databases provide an important opportunity to identify a sufficient number of patients for research, patient registries, or quality improvement work. However, the accuracy of CH diagnoses recorded in electronic health record (EHR) databases is unknown. The Research Patient Data Registry (RPDR) warehouses information from EHR of two academic medical centers in Boston. We assessed the validity of CH diagnoses in the RPDR as well as the sensitivity of International Classification of Headache Disorders (ICHD) diagnostic criteria in relation to the gold standard of expert clinician diagnosis of CH. METHODS: In 2013, we queried RPDR to identify all patients diagnosed with CH diagnosed by headache specialists from 2002 to 2012. We sought to determine the positive predictive value (PPV) of an EHR diagnosis of CH relative to a headache expert's clinical impression as the gold standard. We also calculated the sensitivity of ICHD-2 CH criteria compared with the gold standard of expert-diagnosed CH cases. RESULTS: RPDR queries identified 170 patients with a diagnosis of CH. Two researchers carried out a detailed chart review searching for information to support or refute this diagnosis. In 58 cases, the diagnosis of CH was determined to be inaccurate due to data entry errors. The PPV of an RPDR diagnosis of CH was 63% (95% CI 54-71%) and the sensitivity of ICHD-2 criteria compared with the gold standard of expert diagnosis was 77% (95% CI 69-82%). CONCLUSIONS: The PPV of EHR diagnoses of CH is modest. Data entry errors are common, and only about three fourths of CH cases diagnosed by expert clinicians meet ICHD criteria for CH. Thus, EHR searches for patients with CH frequently will result in false positives. This has implications for activities such as research, quality improvement efforts, or disease registries that rely on EHR searches to identify patients. Further work is needed to develop high quality phenotypic algorithms so that the research potential of EHRs can be realized. PMID- 27273525 TI - Enhancement of the properties of a drug by mono-deuteriation: reduction of acid catalysed formation of a gut-motilide enol ether from 8-deuterio-erythromycin B. AB - Erythromycin B is structurally very similar to erythromycin A, and also shares its clinically important antibacterial activity. Its potential advantage is that it is much more stable to acid. Both compounds are susceptible to 6-9-enol ether formation, involving loss of a proton from C-8. The enol ethers lack antibacterial activity and can give rise to unpleasant gut motilide side-effects. Our previous work on degradation kinetics revealed that the formation of erythromycin B enol ether from erythromycin B is subject to a large deuterium isotope effect. We therefore synthesized 8-d-erythromycin B (in 87% yield) in the hope that acid-catalysed enol ether formation would be reduced, relative to erythromycin B. In a range of microbiological and biochemical assays, deuteriation did not appear to compromise the efficacy of the drug. Degradation studies showed, however, that incorporation of deuterium into erythromycin B reduces (though does not completely suppress) enol ether formation, providing the possibility of using a facile mono-deuteriation to reduce the gut motilide side effects of the drug. PMID- 27273527 TI - Announcement from the editorial office: MEDLINE indexing and PubMed. PMID- 27273526 TI - Use of modified Atkins diet in glucose transporter type 1 deficiency syndrome. AB - AIM: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) results from impaired glucose transport into the brain, and is treated with a ketogenic diet. A few reports have suggested effectiveness of treatment using the modified Atkins diet (MAD). We aimed to assess the efficacy of MAD as a treatment for GLUT1-DS. METHOD: We evaluated the efficacy of MAD in 10 patients (four males, six females; mean age at diagnosis [SD] 6.2y [1.7], min-max: 4mo-12y) with GLUT1-DS. RESULTS: MAD was started at diagnosis in eight patients, including two infants. The mean duration (SD) under MAD was 2.5 [0.6] years (range 6mo-6y). Seven patients with epilepsy started MAD at GLUT1-DS diagnosis, and all experienced improvements in their epilepsy: five out of seven were seizure-free at M1, and three out of six at M3 and M6. The initiation of MAD allowed symptoms to be controlled in the three patients with movement disorders but without seizures. Two patients switched from the ketogenic diet to MAD. This switch was not responsible for the recurrence of any symptoms, and led to improvements in both physical abilities and growth parameters. INTERPRETATION: MAD, which is a less restrictive and more palatable diet than the ketogenic diet, seems to have comparable effectiveness. Moreover, a switch from the ketogenic diet to MAD appears to be beneficial for patients with GLUT1-DS. PMID- 27273528 TI - Carotenogenesis diversification in phylogenetic lineages of Rhodophyta. AB - Carotenoid composition is very diverse in Rhodophyta. In this study, we investigated whether this variation is related to the phylogeny of this group. Rhodophyta consists of seven classes, and they can be divided into two groups on the basis of their morphology. The unicellular group (Cyanidiophyceae, Porphyridiophyceae, Rhodellophyceae, and Stylonematophyceae) contained only beta carotene and zeaxanthin, "ZEA-type carotenoids." In contrast, within the macrophytic group (Bangiophyceae, Compsopogonophyceae, and Florideophyceae), Compsopogonophyceae contained antheraxanthin in addition to ZEA-type carotenoids, "ANT-type carotenoids," whereas Bangiophyceae contained alpha-carotene and lutein along with ZEA-type carotenoids, "LUT-type carotenoids." Florideophyceae is divided into five subclasses. Ahnfeltiophycidae, Hildenbrandiophycidae, and Nemaliophycidae contained LUT-type carotenoids. In Corallinophycidae, Hapalidiales and Lithophylloideae in Corallinales contained LUT-type carotenoids, whereas Corallinoideae in Corallinales contained ANT-type carotenoids. In Rhodymeniophycidae, most orders contained LUT-type carotenoids; however, only Gracilariales contained ANT-type carotenoids. There is a clear relationship between carotenoid composition and phylogenetics in Rhodophyta. Furthermore, we searched open genome databases of several red algae for references to the synthetic enzymes of the carotenoid types detected in this study. beta-Carotene and zeaxanthin might be synthesized from lycopene, as in land plants. Antheraxanthin might require zeaxanthin epoxydase, whereas alpha-carotene and lutein might require two additional enzymes, as in land plants. Furthermore, Glaucophyta contained ZEA-type carotenoids, and Cryptophyta contained beta carotene, alpha-carotene, and alloxanthin, whose acetylenic group might be synthesized from zeaxanthin by an unknown enzyme. Therefore, we conclude that the presence or absence of the four enzymes is related to diversification of carotenoid composition in these three phyla. PMID- 27273530 TI - Investigation of the Gracilaria gracilis (Gracilariales, Rhodophyta) proteome response to nitrogen limitation. AB - Inorganic nitrogen has been identified as the major growth-limiting nutritional factor affecting Gracilaria gracilis populations in South Africa. Although the physiological mechanisms implemented by G. gracilis for adaption to low nitrogen environments have been investigated, little is known about the molecular mechanisms of these adaptions. This study provides the first investigation of G. gracilis proteome changes in response to nitrogen limitation and subsequent recovery. A differential proteomics approach employing two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry was used to investigate G. gracilis proteome changes in response to nitrogen limitation and recovery. The putative identity of 22 proteins that changed significantly (P < 0.05) in abundance in response to nitrogen limitation and recovery was determined. The identified proteins function in a range of biological processes including glycolysis, photosynthesis, ATP synthesis, galactose metabolism, protein-refolding and biosynthesis, nitrogen metabolism and cytoskeleton remodeling. The identity of fructose 1,6 biphosphate (FBP) aldolase was confirmed by western blot analysis and the decreased abundance of FBP aldolase observed with two-dimensional gel electrophoresis was validated by enzyme assays and western blots. The identification of key proteins and pathways involved in the G. gracilis nitrogen stress response provide a better understanding of G. gracilis proteome responses to varying degrees of nitrogen limitation and is the first step in the identification of biomarkers for monitoring the nitrogen status of cultivated G. gracilis populations. PMID- 27273529 TI - On the use of high-throughput sequencing for the study of cyanobacterial diversity in Antarctic aquatic mats. AB - The study of Antarctic cyanobacterial diversity has been mostly limited to morphological identification and traditional molecular techniques. High throughput sequencing (HTS) allows a much better understanding of microbial distribution in the environment, but its application is hampered by several methodological and analytical challenges. In this work, we explored the use of HTS as a tool for the study of cyanobacterial diversity in Antarctic aquatic mats. Our results highlight the importance of using artificial communities to validate the parameters of the bioinformatics procedure used to analyze natural communities, since pipeline-dependent biases had a strong effect on the observed community structures. Analysis of microbial mats from five Antarctic lakes and an aquatic biofilm from the Sub-Antarctic showed that HTS is a valuable tool for the assessment of cyanobacterial diversity. The majority of the operational taxonomic units retrieved were related to filamentous taxa such as Leptolyngbya and Phormidium, which are common genera in Antarctic lacustrine microbial mats. However, other phylotypes related to different taxa such as Geitlerinema, Pseudanabaena, Synechococcus, Chamaesiphon, Calothrix, and Coleodesmium were also found. Results revealed a much higher diversity than what had been reported using traditional methods and also highlighted remarkable differences between the cyanobacterial communities of the studied lakes. The aquatic biofilm from the Sub Antarctic had a distinct cyanobacterial community from the Antarctic lakes, which in turn displayed a salinity-dependent community structure at the phylotype level. PMID- 27273531 TI - Nocturama gen. nov., Nothocladus s. lat. and other taxonomic novelties resulting from the further resolution of paraphyly in Australasian members of Batrachospermum (Batrachospermales, Rhodophyta). AB - The informal "Australasica Group" was established in 2009 to include several Australasian endemic Batrachospermum species, a few species of the cosmopolitan Batrachospermum section Setacea, and the South American endemic Petrohua bernabei. Although useful for communication purposes, no formal taxonomic designation was proposed due to weakly supported basal nodes. The present research took a two-pronged approach of adding more taxa (29 additional specimens) as well as more sequence data (LSU, cox1, psaA, and psbA markers added to rbcL data) to provide better resolution. The resulting tree showed improved statistical support values (Bayesian posterior probability and maximum likelihood bootstrap) for most nodes providing a framework for taxonomic revision. Based on our well-resolved phylogeny, a new genus, Nocturama, is proposed for a clade of Batrachospermum antipodites specimens. The circumscription of Nothocladus is expanded to include Batrachospermum section Setacea and four additional sections composed of at least 10 species, mostly from Australia and New Zealand. One new species added to the data set, N. diatyches, did not form a clade with the other species of section Setaceus, where it was classified previously, rendering that section paraphyletic. To resolve this, N. diatyches and the morphologically similar species N. latericius are included with N. theaquus, in the new section Theaquus within Nothocladus s. lat. A specimen from Australia unaligned to these clades was sister to the Australia-New Zealand genus Psilosiphon and the cosmopolitan B. cayennense, but lacked statistical support. This specimen has the gross morphology of Batrachospermum s. lat. and is here provisionally assigned to that genus, as B. serendipidum sp. nov. PMID- 27273533 TI - The chloroplast genome of Phacus orbicularis (Euglenophyceae): an initial datum point for the phacaceae. AB - The Euglenophyceae chloroplast was acquired when a heterotrophic euglenoid engulfed a green alga and subsequently retained the algal chloroplast, in a process known as secondary endosymbiosis. Since this event, Euglenophyceae have diverged widely and their chloroplast genomes (cpGenomes) have as well. Changes to the cpGenome include extensive gene rearrangement and the proliferation of introns, the analyses of which have proven to be useful in examining cpGenome changes throughout the Euglenophyceae. The Euglenales fall into two families, Euglenaceae and Phacaceae. Euglenaceae contains eight genera and at least one cpGenome has been published for each genus. Phacaceae, on the other hand, contains three genera, none of which have had a representative chloroplast genome sequenced. Members of this family have many small disk-shaped chloroplasts that lack pyrenoids. We sequenced and annotated the cpGenome of Phacus orbicularis in order to fill in the large gap in our understanding of Euglenophyceae cpGenome evolution, especially in regard to intron number and gene order. We compared this cpGenome to those of species from both the Euglenaceae and Eutreptiales of the Euglenophyceae phylogenetic tree. The cpGenome showed characteristics that were more derived than that of the basal species Eutreptia viridis, with extensive gene rearrangements and nearly three times as many introns. In contrast, it contained fewer introns than all but one of the previously reported Euglenaceae cpGenomes, had a smaller estimated genome size, and shared greater synteny with two main branches of that family. PMID- 27273532 TI - Rhodenigma contortum, an obscure new genus and species of Rhodogorgonales (Rhodophyta) from Western Australia. AB - An unknown microscopic, branched filamentous red alga was isolated into culture from coral fragments collected in Coral Bay, Western Australia. It grew well unattached or attached to glass with no reproduction other than fragmentation of filaments. Cells of some branch tips became slightly contorted and digitated, possibly as a substrate-contact-response seen at filament tips of various algae. Attached multicellular compact disks on glass had a very different cellular configuration and size than the free filaments. In culture the filaments did not grow on or in coral fragments. Molecular phylogenies based on four markers (rbcL, cox1, 18S, 28S) clearly showed it belongs to the order Rhodogorgonales, as a sister clade of Renouxia. Based on these results, the alga is described as the new genus and species Rhodenigma contortum in the Rhodogorgonaceae. It had no morphological similarity to either of the other genera in Rhodogorgonaceae and illustrates the unknown diversity in cryptic habitats such as tropical coral rubble. PMID- 27273534 TI - Phylogenetic relationships of corallinaceae (Corallinales, Rhodophyta): taxonomic implications for reef-building corallines. AB - A new, more complete, five-marker (SSU, LSU, psbA, COI, 23S) molecular phylogeny of the family Corallinaceae, order Corallinales, shows a paraphyletic grouping of seven well-supported monophyletic clades. The taxonomic implications included the amendment of two subfamilies, Neogoniolithoideae and Metagoniolithoideae, and the rejection of Porolithoideae as an independent subfamily. Metagoniolithoideae contained Harveylithon gen. nov., with H. rupestre comb. nov. as the generitype, and H. canariense stat. nov., H. munitum comb. nov., and H. samoense comb. nov. Spongites and Pneophyllum belonged to separate clades. The subfamily Neogoniolithoideae included the generitype of Spongites, S. fruticulosus, for which an epitype was designated. Pneophyllum requires reassesment. The generitype of Hydrolithon, H. reinboldii, was a younger heterotypic synonym of H. boergesenii. The evolutionary novelty of the subfamilies Hydrolithoideae, Metagoniolithoideae, and Lithophylloideae was the development of tetra/bisporangial conceptacle roofs by filaments surrounding and interspersed among the sporangial initials. PMID- 27273535 TI - Temperature-dependent phagotrophy and phototrophy in a mixotrophic chrysophyte. AB - The roles of temperature and light on grazing and photosynthesis were examined for Dinobryon sociale, a common freshwater mixotrophic alga. Photosynthetic rate was determined for D. sociale adapted to temperatures of 8, 12, 16, and 20 degrees C under photosynthetically active radiation light irradiances of 25, 66, and 130 MUmol photons . m(-2) . s(-1) , with concurrent measurement of bacterial ingestion at all temperatures under medium and high light (66 and 130 MUmol photons . m(-2) . s(-1) ). Rates of ingestion and photosynthesis increased with temperature to a maximum at 16 degrees C under the two higher light regimes, and declined at 20 degrees C. Although both light and temperature had a marked effect on photosynthesis, there was no significant difference in bacterivory at medium and high irradiances at any given temperature. At the lowest light condition (25 MUmol photons . m(-2) . s(-1) ), photosynthesis remained low and relatively stable at all temperatures. D. sociale acquired the majority of carbon from photosynthesis, although the low photosynthetic rate without a concurrent decline in feeding rate at 8 degrees C suggested 20%-30% of the carbon budget could be attributed to bacterivory at low temperatures. Grazing experiments in nutrient modified media revealed that this mixotroph had increased ingestion rates when either dissolved nitrogen or phosphorus was decreased. This work increases our understanding of environmental effects on mixotrophic nutrition. Although the influence of abiotic factors on phagotrophy and phototrophy in pure heterotrophs and phototrophs has been well studied, much less is known for mixotrophic organisms. PMID- 27273536 TI - The complete chloroplast genome of Gracilariopsis lemaneiformis (Rhodophyta) gives new insight into the evolution of family Gracilariaceae. AB - The complete chloroplast genome of Gracilariopsis lemaneiformis was recovered from a Next Generation Sequencing data set. Without quadripartite structure, this chloroplast genome (183,013 bp, 27.40% GC content) contains 202 protein-coding genes, 34 tRNA genes, 3 rRNA genes, and 1 tmRNA gene. Synteny analysis showed plasmid incorporation regions in chloroplast genomes of three species of family Gracilariaceae and in Grateloupia taiwanensis of family Halymeniaceae. Combined with reported red algal plasmid sequences in nuclear and mitochondrial genomes, we postulated that red algal plasmids may have played an important role in ancient horizontal gene transfer among nuclear, chloroplast, and mitochondrial genomes. Substitution rate analysis showed that purifying selective forces maintaining stability of protein-coding genes of nine red algal chloroplast genomes over long periods must be strong and that the forces acting on gene groups and single genes of nine red algal chloroplast genomes were similar and consistent. The divergence of Gp. lemaneiformis occurred ~447.98 million years ago (Mya), close to the divergence time of genus Pyropia and Porphyra (443.62 Mya). PMID- 27273537 TI - A new type of 3-D peripheral ultrastructure in Glaucocystis (Glaucocystales, Glaucophyta) as revealed by ultra-high voltage electron microscopy. AB - The coccoid glaucophyte genus Glaucocystis is characterized by having a thick cell wall, which has to date prohibited examination of the native ultrastructural features of the protoplast periphery. Recently, however, the three-dimensional (3 D) ultrastructure of the protoplast periphery was revealed in two divergent Glaucocystis species, with the world's most powerful ultra-high voltage electron microscope (UHVEM). The two species exhibit morphological diversity in terms of their 3-D ultrastructural features. However, these two types do not seem to encompass actual ultrastructural diversity in the genetically diverse genus Glaucocystis. Here, we report a new type of peripheral 3-D ultrastructure resolved in "G. incrassata" SAG 229-2 cells by 3-D modeling based on UHVEM tomography using high-pressure freezing and freeze-substitution fixation. The plasma membrane and underlying flattened vesicles in "G. incrassata" SAG 229-2 exhibited grooves at intervals of 200-600 nm, and the flattened vesicles often overlapped one another at the protoplast periphery. This 3-D ultrastructure differs from those of the two types previously reported in other species of Glaucocystis. The possibility of classification of Glaucocystis species based on the 3-D ultrastructure of the protoplast periphery is discussed. PMID- 27273538 TI - Arabidopsis LBP/BPI related-1 and -2 bind to LPS directly and regulate PR1 expression. AB - Lipopolysaccharide (LPS) is a major constituent of the outer membrane of Gram negative bacteria and acts as a pathogen-associated molecular pattern that triggers immune responses in both plants and animals. LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI), which bind to LPS and play important roles in immunity of mammals, have been well studied. However, the molecule contributing to LPS binding in plants is mostly unknown. The Arabidopsis genome carries two genes encoding LBP/BPI-related proteins which we designated as AtLBP/BPI related-1 (AtLBR-1) and AtLBP/BPI related-2 (AtLBR-2). We found that their N-terminal domains were co-purified with cell wall-derived LPS when expressed in E. coli. Since this finding implied the direct binding of AtLBRs to LPS, we also confirmed binding by using LPS-free AtLBRs and purified LPS. AtLBRs directly bind to both rough and smooth types of LPS. We also demonstrated that LPS-treated atlbr mutant Arabidopsis exhibit a significant delay of induction of defence-related gene pathogenesis-related 1 (PR1) but no other PR genes. Furthermore, LPS-treated atlbr mutants showed defects in reactive oxygen species (ROS) generation. These results demonstrate that, as well as LBP and BPI of mammals, AtLBRs also play an important role in the LPS-induced immune response of plants. PMID- 27273539 TI - The antihypertensive drug pindolol attenuates long-term but not short-term binge like ethanol consumption in mice. AB - Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12 weeks) binge-ethanol intake, compared with short term (4 weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency of BLA principal neurons from long-term ethanol-consuming mice but not naive mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies. PMID- 27273540 TI - Assessment of Arterial Stiffness in Korean Patients With Psoriasis by Cardio Ankle Vascular Index. AB - Many recent studies have suggested that psoriasis, a chronic, inflammatory, immune-mediated skin disease, is associated with increased risk of cardiovascular disease (CVD). We aimed to compare arterial stiffness in psoriasis and control patient groups using the cardio-ankle vascular index (CAVI) and to determine whether psoriasis is an independent risk factor for CVD. A total 103 patients with psoriasis and 103 age- and sex-matched controls were enrolled. Compared with controls, the patients showed a higher CAVI ( P = .03), particularly patients older than 40 years. The duration of psoriasis exhibited a positive correlative tendency with CAVI ( P = .066). Moreover, psoriasis is an independent predictor of arterial stiffness after adjusting for other factors ( P = .011). We suggest that psoriasis can be a risk factor for CVD, and older patients with psoriasis of longer disease duration should be monitored carefully for cardiovascular risk. PMID- 27273549 TI - Syphilis Screening in Neurology. PMID- 27273550 TI - Detection of Burkholderia pseudomallei toxin-mediated inhibition of protein synthesis using a Caenorhabditis elegans ugt-29 biosensor. AB - Toxins are believed to play a crucial role in Burkholderia pseudomallei pathogenicity, however to date, only a few have been identified. The discovery of additional toxic molecules is limited by the lack of a sensitive indicator of B. pseudomallei toxicity. Previously, from a whole genome transcriptome analysis of B. pseudomallei-infected Caenorhabditis elegans, we noted significant overexpression of a number of worm genes encoding detoxification enzymes, indicating the host's attempt to clear bacterial toxic molecules. One of these genes, ugt-29, a family member of UDP-glucuronosyltransferases, was the most robustly induced phase II detoxification gene. In this study, we show that strong induction of ugt-29 is restricted to infections by the most virulent species among the pathogens tested. We also noted that ugt-29 is activated upon disruption of host protein synthesis. Hence, we propose that UGT-29 could be a promising biosensor to detect B. pseudomallei toxins that compromise host protein synthesis. The identification of bactobolin, a polyketide-peptide hybrid molecule, as a toxic molecule of B. pseudomallei further verifies the utilization of this surveillance system to search for bacterial toxins. Hence, a ugt-29 based reporter should be useful in screening for other molecules that inhibit host protein synthesis. PMID- 27273551 TI - Artichoke and milk thistle pills and syrups as sources of phenolic compounds with antimicrobial activity. AB - Dietary supplements based on hepatoprotective plants have been increasingly used in the prevention of liver injuries. In the present work, the aim was to study the phenolic profile and possibly relate it to the in vitro antimicrobial activity of two different formulations (pills and syrups) of artichoke and milk thistle, the antioxidant and anti-hepatocellular carcinoma activities of which were previously reported by our research group. The phenolic profiles were obtained by HPLC-DAD-ESI/MS, and the antimicrobial activity evaluation was performed with the clinical isolates of multiresistant bacteria (Escherichia coli, extended spectrum beta-lactamases (ESBL) producing Escherichia coli, Proteus mirabilis, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa). Artichoke syrup revealed the presence of vanillic acid and luteolin-7-O-glucoside while the pills possessed higher concentrations of 4-O caffeoylquinic, 5-O-caffeoylquinic and 1,3-O-dicaffeoylquinic acids, this latest being able to inhibit the growth of MRSA. Regarding milk thistle formulations, the syrup presented isorhamnetin-O-deoxyhexoside-O-dihexoside, isorhamnetin-O deoxyhexoside-O-hexoside and isorhamnetin-3-O-rutinoside as the major phenolic constituents whereas the pills were richer in taxifolin, silymarin derivatives and hydroxylated silibinin; the syrup revealed antimicrobial activity against all the studied bacteria with the exception of Proteus mirabilis whereas the pills revealed activity against ESBL producing Escherichia coli. Overall, all of the studied formulations revealed to be a good source of phenolic compounds, among which milk thistle syrup presented the highest variety and concentration of flavonoids, which is possibly related to its strongest antimicrobial activity. PMID- 27273552 TI - Proinflammatory signaling regulates voluntary alcohol intake and stress-induced consumption after exposure to social defeat stress in mice. AB - Proinflammatory activity has been postulated to play a role in addictive processes and stress responses, but the underlying mechanisms remain largely unknown. Here, we examined the role of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in regulation of voluntary alcohol consumption, alcohol reward and stress-induced drinking. Mice with a deletion of the IL-1 receptor I gene (IL-1RI KO) exhibited modestly decreased alcohol consumption. However, IL 1RI deletion affected neither the rewarding properties of alcohol, measured by conditioned place preference (CPP), nor stress-induced drinking induced by social defeat stress. TNF-alpha signaling can compensate for phenotypic consequences of IL1-RI deletion. We therefore hypothesized that double deletion of both IL-1RI and TNF-1 receptors (TNF-1R) may reveal the role of these pathways in regulation of alcohol intake. Double KOs consumed significantly less alcohol than control mice over a range of alcohol concentrations. The combined deletion of TNF-1R and IL-1RI did not influence alcohol reward, but did prevent increased alcohol consumption resulting from exposure to repeated bouts of social defeat stress. Taken together, these data indicate that IL-1RI and TNF-1R contribute to regulation of stress-induced, negatively reinforced drinking perhaps through overlapping signaling events downstream of these receptors, while leaving rewarding properties of alcohol largely unaffected. PMID- 27273554 TI - 2D-Crystal-Based Functional Inks. AB - The possibility to produce and process graphene, related 2D crystals, and heterostructures in the liquid phase makes them promising materials for an ever growing class of applications as composite materials, sensors, in flexible optoelectronics, and energy storage and conversion. In particular, the ability to formulate functional inks with on-demand rheological and morphological properties, i.e., lateral size and thickness of the dispersed 2D crystals, is a step forward toward the development of industrial-scale, reliable, inexpensive printing/coating processes, a boost for the full exploitation of such nanomaterials. Here, the exfoliation strategies of graphite and other layered crystals are reviewed, along with the advances in the sorting of lateral size and thickness of the exfoliated sheets together with the formulation of functional inks and the current development of printing/coating processes of interest for the realization of 2D-crystal-based devices. PMID- 27273553 TI - Structural characterization of the heme-based oxygen sensor, AfGcHK, its interactions with the cognate response regulator, and their combined mechanism of action in a bacterial two-component signaling system. AB - The oxygen sensor histidine kinase AfGcHK from the bacterium Anaeromyxobacter sp. Fw 109-5 forms a two-component signal transduction system together with its cognate response regulator (RR). The binding of oxygen to the heme iron of its N terminal sensor domain causes the C-terminal kinase domain of AfGcHK to autophosphorylate at His183 and then transfer this phosphate to Asp52 or Asp169 of the RR protein. Analytical ultracentrifugation revealed that AfGcHK and the RR protein form a complex with 2:1 stoichiometry. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) suggested that the most flexible part of the whole AfGcHK protein is a loop that connects the two domains and that the heme distal side of AfGcHK, which is responsible for oxygen binding, is the only flexible part of the sensor domain. HDX-MS studies on the AfGcHK:RR complex also showed that the N-side of the H9 helix in the dimerization domain of the AfGcHK kinase domain interacts with the helix H1 and the beta-strand B2 area of the RR protein's Rec1 domain, and that the C-side of the H8 helix region in the dimerization domain of the AfGcHK protein interacts mostly with the helix H5 and beta-strand B6 area of the Rec1 domain. The Rec1 domain containing the phosphorylable Asp52 of the RR protein probably has a significantly higher affinity for AfGcHK than the Rec2 domain. We speculate that phosphorylation at Asp52 changes the overall structure of RR such that the Rec2 area containing the second phosphorylation site (Asp169) can also interact with AfGcHK. Proteins 2016; 84:1375-1389. (c) 2016 Wiley Periodicals, Inc. PMID- 27273556 TI - The bronchodilator response in preschool children: A systematic review. AB - BACKGROUND: The bronchodilator response (BDR) is frequently used to support diagnostic and therapeutic decision-making for children who wheeze. However, there is little evidence-based guidance describing the role of BDR testing in preschool children and it is unclear whether published cut-off values, which are derived from adult data, can be applied to this population. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane databases (inception-September 2015) for studies reporting response to a bronchodilator in healthy preschool children, response following placebo inhalation, and the diagnostic efficacy of BDR compared with a clinical diagnosis of asthma/recurrent wheezing. FINDINGS: We included 14 studies. Thirteen studies provided BDR data from healthy preschool children. Two studies reported response to placebo in preschool children with asthma/recurrent wheezing. Twelve studies compared BDR measurements from preschool children with asthma/recurrent wheeze to those from healthy children and seven of these studies reported diagnostic efficacy. Significant differences between the BDR measured in healthy preschool children compared with that in children with asthma/recurrent wheeze were demonstrated in some, but not all studies. Techniques such as interrupter resistance, oscillometry, and plethysmography were more consistently successfully completed than spirometry. Between study heterogeneity precluded determination of an optimum technique. INTERPRETATION: There is little evidence to suggest spirometry-based BDR can be used in the clinical assessment of preschool children who wheeze. Further evaluation of simple alternative techniques is required. Future studies should recruit children in whom airways disease is suspected and should evaluate the ability of BDR testing to predict treatment response. Pediatr Pulmonol. 2016;51:1242-1250. (c) 2016 Wiley Periodicals, Inc. PMID- 27273557 TI - Predicting Success in Psychological Statistics Courses. AB - Many students perform poorly in courses on psychological statistics, and it is useful to be able to predict which students will have difficulties. In a study of 93 undergraduates enrolled in Statistical Methods (18 men, 75 women; M age = 22.0 years, SD = 5.1), performance was significantly associated with sex (female students performed better) and proficiency in algebra in a linear regression analysis. Anxiety about statistics was not associated with course performance, indicating that basic mathematical skills are the best correlate for performance in statistics courses and can usefully be used to stream students into classes by ability. PMID- 27273555 TI - Model-based exposure-response analysis to quantify age related differences in the response to scopolamine in healthy subjects. AB - AIM: Subjects with increasing age are more sensitive to the effects of the anti muscarinic agent scopolamine, which is used (among other indications) to induce temporary cognitive dysfunction in early phase drug studies with cognition enhancing compounds. The enhanced sensitivity has always been attributed to incipient cholinergic neuronal dysfunction, as a part of the normal aging process. The aim of the study was to correlate age-dependent pharmacodynamic neuro-physiologic effects of scopolamine after correcting for differences in individual exposure. METHODS: We applied a pharmacokinetic and pharmacodynamic modelling approach to describe individual exposure and neurocognitive effects of intravenous scopolamine administration in healthy subjects. RESULTS: A two compartment linear kinetics model best described the plasma concentrations of scopolamine. The estimated scopolamine population mean apparent central and peripheral volume of distribution was 2.66 +/- 1.050 l and 62.10 +/- 10.100 l, respectively and the clearance was 1.09 +/- 0.096 l min(-1) . Age was not related to a decrease of performance in the tests following scopolamine administration in older subjects. Only the saccadic peak velocity showed a positive correlation between age and sensitivity to scopolamine. Age was, however, correlated at baseline with an estimated slower reaction time while performing the cognitive tests and to higher global delta and frontal theta frequency bands measured with the surface EEG. CONCLUSIONS: Most of the differences in response to scopolamine administration between young and older subjects could be explained by pharmacokinetic differences (lower clearance) and not to an enhanced sensitivity when corrected for exposure levels. PMID- 27273558 TI - Validating the Executive Personal Finance Scale with Financial Investments and Expectations in University Students. AB - The validity of the Executive Personal Finance Scale (EPFS) was tested in a sample of 93 undergraduate students (31 men, 62 women; M age = 20.5 years, SD = 1.3, range = 18-24). Scores on the Motivation drive, Organization, and Planning subscales of this scale were associated with having a savings account, owning bank CDs, and self-estimated knowledge about financial matters, while scores on the Impulse control and Motivational drive subscales were associated with expectations for a satisfactory retirement income. The results provide support for the validity of the EPFS. PMID- 27273559 TI - Homonegative Attitudes and their Correlates Among Vietnamese College Students. AB - This study investigated sex differences in homonegativity and their correlates among 197 Vietnamese college students (males = 49, females = 148, M = 20.9 years, SD = 2.9) in Ho Chi Minh City. The survey included Vietnamese-language versions of four scales measuring attitudes toward homosexuality (ATHS), traditional masculinity ideology, knowledge of homosexuality, and contact experiences with homosexuals. An exploratory factor analysis indicated a 3-factor structure for the ATHS: Homonegativity, Tolerance, and Positive Images. Male respondents reported significantly higher scores on homonegativity. Traditional masculinity ideology was positively related to females' homonegativity, but negatively correlated with tolerant attitudes of both males and females. Knowledge about homosexuality was negatively correlated with homonegativity. Media contact with homosexuals was negatively correlated with males' homonegativity, but positively correlated with both females and males' tolerant attitudes. Results suggest that future research develop a new scale to measure Vietnamese's homonegativity and that media contact as well as ample and accurate knowledge about homosexuality can alter homonegativity. PMID- 27273560 TI - Comparing American State Resident Neuroticism and State Tightness-Looseness as Predictors of Annual State Residential Mobility. AB - State resident neuroticism and the Harrington and Gelfand state tightness looseness dimension were compared as predictors of state levels of residential mobility from 2004 to 2005 in the 50 American states. Hierarchical multiple regression controlled for state SES, white population percent, urban population percent, home ownership percent, and percent of home owners or renters paying 30 percent or more of household income for housing. Not moving was associated with higher neuroticism but not with tightness-looseness. Same-county moving, different-county moving, and within-state moving was associated with lower neuroticism but tightness-looseness was unrelated to any of these three criteria. However, lower tightness was associated with different-state moving and higher tightness was associated with greater tendency to move within a state rather than to a different state. Neuroticism showed no relation to the ratio of different state to same-state moving. Results suggest distance moved may determine when neuroticism or tightness-looseness is a residential mobility predictor. PMID- 27273561 TI - Nasopharynx is well-suited for core temperature measurement during hypothermia therapy. AB - BACKGROUND: Rectal temperature is commonly used as the core temperature during therapeutic hypothermia therapy in neonates with hypoxic-ischemic encephalopathy (HIE). The purpose of this study was to examine whether nasopharyngeal temperature could serve as a substitute for rectal temperature. METHODS: We prospectively investigated 40 neonates with HIE who underwent therapeutic hypothermia by selective head cooling, which involved cooling the body to 34 degrees C for 72 h. During this period, nasopharyngeal temperature was measured and compared with rectal temperature every hour. RESULTS: For 40 neonates included in this study, the mean rectal and nasopharyngeal temperatures were 34.3 +/- 0.4 degrees C (n = 2920) and 34.3 +/- 0.4 degrees C (n = 2920), respectively. Nasopharyngeal temperature strongly correlated with rectal temperature (R2 = 0.623, P < 0.0001) and magnitude of the mean difference between nasopharyngeal and rectal temperature varied little during the 72 h of therapeutic hypothermia. CONCLUSIONS: Nasopharyngeal temperature in neonates with perinatal HIE undergoing therapeutic hypothermia may be a suitable substitute for rectal temperature. PMID- 27273562 TI - Who is Guilty of Subclinical Atherosclerosis in Prediabetes? Chicken or Egg Causality Paradox Between Insulin Resistance and Epicardial Fat. PMID- 27273564 TI - Energetic Trinitro- and Fluorodinitroethyl Ethers of 1,2,4,5-Tetrazines. AB - Several new energetic ethyl ethers of 1,2,4,5-tetrazine have been synthesized. These molecules display good thermal stability, good oxygen balance, and high densities. Included in these studies are a 2,2,2-trinitroethoxy 1,2,4,5-tetrazine and two fluorodinitroethoxy 1,2,4,5-tetrazines. One of these compounds was converted into the di-N-oxide derivative. The sensitivity of these materials towards destructive stimuli was determined, and overall the materials show promising energetic performance properties. PMID- 27273563 TI - Suppressing epileptic activity in a neural mass model using a closed-loop proportional-integral controller. AB - Closed-loop control is a promising deep brain stimulation (DBS) strategy that could be used to suppress high-amplitude epileptic activity. However, there are currently no analytical approaches to determine the stimulation parameters for effective and safe treatment protocols. Proportional-integral (PI) control is the most extensively used closed-loop control scheme in the field of control engineering because of its simple implementation and perfect performance. In this study, we took Jansen's neural mass model (NMM) as a test bed to develop a PI type closed-loop controller for suppressing epileptic activity. A graphical stability analysis method was employed to determine the stabilizing region of the PI controller in the control parameter space, which provided a theoretical guideline for the choice of the PI control parameters. Furthermore, we established the relationship between the parameters of the PI controller and the parameters of the NMM in the form of a stabilizing region, which provided insights into the mechanisms that may suppress epileptic activity in the NMM. The simulation results demonstrated the validity and effectiveness of the proposed closed-loop PI control scheme. PMID- 27273565 TI - Platelet aggregation and serum adenosine deaminase (ADA) activity in pregnancy associated with diabetes, hypertension and HIV. AB - Platelet aggregation and adenosine deaminase (ADA) activity were evaluated in pregnant women living with some disease conditions including hypertension, diabetes mellitus and human immunodeficiency virus infection. The subject population is consisted of 15 non-pregnant healthy women [control group (CG)], 15 women with normal pregnancy (NP), 7 women with hypertensive pregnancy (HP), 10 women with gestational diabetes mellitus (GDM) and 12 women with human immunodeficiency virus-infected pregnancy (HIP) groups. The aggregation of platelets was checked using an optical aggregometer, and serum ADA activity was determined using the colorimetric method. After the addition of 5 uM of agonist adenosine diphosphate, the percentage of platelet aggregation was significantly (p < 0.05) increased in NP, HP, GDM and HIP groups when compared with the CG, while the addition of 10 uM of the same agonist caused significant (p < 0.05) elevations in HP, GDM and HIP groups when compared with CG. Furthermore, ADA activity was significantly (p < 0.05) enhanced in NP, HP, GDM and HIP groups when compared with CG. In this study, the increased platelet aggregation and ADA activity in pregnancy and pregnancy-associated diseases suggest that platelet aggregation and ADA activity could serve as peripheral markers for the development of effective therapy in the maintenance of homeostasis and some inflammatory process in these pathophysiological conditions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273566 TI - Modification with Metallic Bismuth as Efficient Strategy for the Promotion of Photocatalysis: The Case of Bismuth Phosphate. AB - A BiPO4 nanostructure modified with Bi nanoparticles rich in oxygen vacancies in the surface and subsurface was prepared through a one-pot solvothermal treatment utilizing the weak reductive ability of ethylene glycol (EG). The presence of Bi nanocrystals and oxygen vacancies is beneficial for the separation and consumption of photogenerated electrons and holes where Bi nanocrystals act as active sites for the formation of (.) OH and oxygen vacancies are active sites for (.) O2 (-) formation. The enhanced photocatalytic activity is ascribed to the synergistic effect of Bi nanocrystals and surface oxygen vacancies. PMID- 27273567 TI - Steroid therapy and conduction disturbances after transcatheter aortic valve implantation. AB - BACKGROUND: Direct mechanical compression of the frame struts on the adjacent bundle branch with local inflammatory reaction might cause conduction system disturbances and need for pacemaker implantation following transcatheter aortic valve implantation (TAVI). We assessed the impact of preprocedural anti inflammatory steroid therapy on the occurrence of conduction disturbances following TAVI. METHODS AND RESULTS: From a cohort of 324 patients who underwent transfemoral TAVI, 39 (12%) were pretreated with steroids because of iodine allergy (n=29) or active obstructive pulmonary disease (n=10). We compared the rate of occurrence of new conduction disturbances and pacemaker implantation between TAVI patients with (n=39) and without (n=285) steroid treatment, using Cox logistic regression estimates and proportional hazards models. The overall occurrence of new conduction defects and the need for new pacemaker implantation were similar among steroid and non-steroid-treated patients (38.4% vs 37.5% and 25.6% vs 25.3%, respectively). New conduction disturbances were more prevalent in patients treated with CoreValve prosthesis, low implantation, and smaller aortic annulus diameter (P<.001, P<.001, and P=.006, respectively). Thirty-day mortality and complication rates were similar between the groups. CONCLUSION: Although safe, steroid treatment prior to TAVI failed to reduce the incidence of new conduction defects and the need for pacemaker implantation. PMID- 27273568 TI - Secondary electrospray ionization coupled to high-resolution mass spectrometry reveals tryptophan pathway metabolites in exhaled human breath. AB - Many studies and personalized medicine in general require frequent measurements and/or rapid results of biomarker levels. Here we show that 20 low volatility metabolites of the tryptophan pathway can be detected in exhaled human breath. This real-time and non-invasive method offers an attractive alternative to blood analysis. PMID- 27273572 TI - A Widespread Pruritic Rash With Facial Swelling and Black Streaks. PMID- 27273573 TI - Newborn Screening. PMID- 27273569 TI - Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. AB - A common genetic form of Parkinson's disease (PD) is caused by mutations in LRRK2. We identify WSB1 as a LRRK2 interacting protein. WSB1 ubiquitinates LRRK2 through K27 and K29 linkage chains, leading to LRRK2 aggregation and neuronal protection in primary neurons and a Drosophila model of G2019S LRRK2. Knocking down endogenous WSB1 exacerbates mutant LRRK2 neuronal toxicity in neurons and the Drosophila model, indicating a role for endogenous WSB1 in modulating LRRK2 cell toxicity. WSB1 is in Lewy bodies in human PD post-mortem tissue. These data demonstrate a role for WSB1 in mutant LRRK2 pathogenesis, and suggest involvement in Lewy body pathology in sporadic PD. Our data indicate a role in PD for ubiquitin K27 and K29 linkages, and suggest that ubiquitination may be a signal for aggregation and neuronal protection in PD, which may be relevant for other neurodegenerative disorders. Finally, our study identifies a novel therapeutic target for PD. PMID- 27273574 TI - Transcription factors AS1 and AS2 interact with LHP1 to repress KNOX genes in Arabidopsis. AB - Polycomb group proteins are important repressors of numerous genes in higher eukaryotes. However, the mechanism by which Polycomb group proteins are recruited to specific genes is poorly understood. In Arabidopsis, LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), also known as TERMINAL FLOWER 2, was originally proposed as a subunit of polycomb repressive complex 1 (PRC1) that could bind the tri methylated lysine 27 of histone H3 (H3K27me3) established by the PRC2. In this work, we show that LHP1 mainly functions with PRC2 to establish H3K27me3, but not with PRC1 to catalyze monoubiquitination at lysine 119 of histone H2A. Our results show that complexes of the transcription factors ASYMMETRIC LEAVES 1 (AS1) and AS2 could help to establish the H3K27me3 modification at the chromatin regions of Class-I KNOTTED1-like homeobox (KNOX) genes BREVIPEDICELLUS and KNAT2 via direct interactions with LHP1. Additionally, our transcriptome analysis indicated that there are probably more common target genes of AS1 and LHP1 besides Class-I KNOX genes during leaf development in Arabidopsis. PMID- 27273575 TI - Mesoscopic bar magnet based on epsilon-Fe2O3 hard ferrite. AB - Ferrite magnets have a long history. They are used in motors, magnetic fluids, drug delivery systems, etc. Herein we report a mesoscopic ferrite bar magnet based on rod-shaped epsilon-Fe2O3 with a large coercive field (>25 kOe). The epsilon-Fe2O3-based bar magnet is a single crystal with a single magnetic domain along the longitudinal direction. A wide frequency range spectroscopic study shows that the crystallographic a-axis of epsilon-Fe2O3, which corresponds to the longitudinal direction of the bar magnet, plays an important role in linear and non-linear magneto-optical transitions, phonon modes, and the magnon (Kittel mode). Due to its multiferroic property, a magnetic-responsive non-linear optical sheet is manufactured as an application using an epsilon-Fe2O3-based bar magnet, resin, and polyethylene terephthalate. Furthermore, from the viewpoint of the large coercive field property, we demonstrate that a mesoscopic epsilon-Fe2O3 bar magnet can be used as a magnetic force microscopy probe. PMID- 27273576 TI - The T300A Crohn's disease risk polymorphism impairs function of the WD40 domain of ATG16L1. AB - A coding polymorphism of human ATG16L1 (rs2241880; T300A) increases the risk of Crohn's disease and it has been shown to enhance susceptibility of ATG16L1 to caspase cleavage. Here we show that T300A also alters the ability of the C terminal WD40-repeat domain of ATG16L1 to interact with an amino acid motif that recognizes this region. Such alteration impairs the unconventional autophagic activity of TMEM59, a transmembrane protein that contains the WD40 domain-binding motif, and disrupts its normal intracellular trafficking and its ability to engage ATG16L1 in response to bacterial infection. TMEM59-induced autophagy is blunted in cells expressing the fragments generated by caspase processing of the ATG16L1-T300A risk allele, whereas canonical autophagy remains unaffected. These results suggest that the T300A polymorphism alters the function of motif containing molecules that engage ATG16L1 through the WD40 domain, either by influencing this interaction under non-stressful conditions or by inhibiting their downstream autophagic signalling after caspase-mediated cleavage. PMID- 27273578 TI - Controllable Electronic Structures and Photoinduced Processes of Bay-Linked Perylenediimide Dimers and a Ferrocene-Linked Triad. AB - A series of perylene-3,4,9,10-bis(dicarboximide) (PDI) dimers linked through the bay regions was systematically synthesized to examine the electronic structures and photophysical properties in dependence on the distance and orientation between the two PDI units. The spectroscopic and electrochemical measurements suggested that the coupling value of a directly linked PDI dimer (PDI)2 is much larger than those of para- and meta-phenylene-bridged PDI dimers p-(PDI)2 and m (PDI)2 . The width of Davydov splitting was quantitatively evaluated to compare the coupling values between the two PDI units in these dimers by absorption spectroscopy in frozen 2-methyl-THF. Excimer formation of PDI dimers induced the strong fluorescence quenching and large red-shifts. Femtosecond transient absorption revealed a broad absorption derived from an excimer in the range from about 600 nm to the near-IR region. The rate constants of formation and decay of the excimer are strongly dependent on the coupling values. Time-resolved measurements on ferrocene-linked p-(PDI)2 revealed a competition between the photoinduced processes of electron transfer and excimer formation in PhCN, which is in sharp contrast with the sole electron-transfer process in toluene. PMID- 27273577 TI - Resting-state functional connectivity and motor imagery brain activation. AB - Motor imagery (MI) relies on the mental simulation of an action without any overt motor execution (ME), and can facilitate motor learning and enhance the effect of rehabilitation in patients with neurological conditions. While functional magnetic resonance imaging (fMRI) during MI and ME reveals shared cortical representations, the role and functional relevance of the resting-state functional connectivity (RSFC) of brain regions involved in MI is yet unknown. Here, we performed resting-state fMRI followed by fMRI during ME and MI with the dominant hand. We used a behavioral chronometry test to measure ME and MI movement duration and compute an index of performance (IP). Then, we analyzed the voxel-matched correlation between the individual MI parameter estimates and seed based RSFC maps in the MI network to measure the correspondence between RSFC and MI fMRI activation. We found that inter-individual differences in intrinsic connectivity in the MI network predicted several clusters of activation. Taken together, present findings provide first evidence that RSFC within the MI network is predictive of the activation of MI brain regions, including those associated with behavioral performance, thus suggesting a role for RSFC in obtaining a deeper understanding of neural substrates of MI and of MI ability. Hum Brain Mapp 37:3847-3857, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273579 TI - Association of Biomarker-Based Treatment Strategies With Response Rates and Progression-Free Survival in Refractory Malignant Neoplasms: A Meta-analysis. AB - Importance: The impact of a biomarker-based (personalized) cancer treatment strategy in the setting of phase 1 clinical trials was analyzed. Objective: To compare patient outcomes in phase 1 studies that used a biomarker selection strategy with those that did not. Data Sources: PubMed search of phase 1 cancer drug trials (January 1, 2011, through December 31, 2013). Study Selection: Studies included trials that evaluated single agents, and reported efficacy end points (at least response rate [RR]). Data Extraction and Synthesis: Data were extracted independently by 2 investigators. Main Outcomes and Measures: Response rate and progression-free survival (PFS) were compared for arms that used a personalized strategy (biomarker selection) vs those that did not. Overall survival was not analyzed owing to insufficient data. Results: A total of 346 studies published in the designated 3-year time period were included in the analysis. Multivariable analysis (meta-regression and weighted multiple regression models) demonstrated that the personalized approach independently correlated with a significantly higher median RR (30.6% [95% CI, 25.0%-36.9%] vs 4.9% [95% CI, 4.2%-5.7%]; P < .001) and a longer median PFS (5.7 [95% CI, 2.6 13.8] vs 2.95 [95% CI, 2.3-3.7] months; P < .001). Targeted therapy arms that used a biomarker-based selection strategy (n = 57 trials) were associated with statistically improved RR compared with targeted therapy arms (n = 177 arms) that did not (31.1% [95% CI, 25.4%-37.4%] vs 5.1% [95% CI, 4.3%-6.0%]; P < .001). Nonpersonalized targeted arms had outcomes comparable with those that tested a cytotoxic agent (median RR, 5.1% [95% CI, 4.3%-6.0%] vs 4.7% [95% CI, 3.6%-6.2%]; P = .63; respectively; median PFS, 3.3 [95% CI, 2.6-4.0] months vs 2.5 [95% CI, 2.0-3.7] months; P = .22). Personalized arms using a "genomic (DNA) biomarker" had higher median RR than those using a "protein biomarker" (42.0% [95% CI, 33.7% 50.9%] vs 22.4% [95% CI, 15.6%-30.9%]; P = .001). The median treatment-related mortality was not statistically different for arms that used a personalized strategy vs not (1.89% [95% CI, 1.36%-2.61%] vs 2.27% [95% CI, 1.97%-2.62%]; P = .31). Conclusions and Relevance: In this meta-analysis, most phase 1 trials of targeted agents did not use a biomarker-based selection strategy. However, use of a biomarker-based approach was associated with significantly improved outcomes (RR and PFS). Response rates were significantly higher with genomic vs protein biomarkers. Studies that used targeted agents without a biomarker had negligible response rates. PMID- 27273580 TI - Myosin XI-I is Mechanically and Enzymatically Unique Among Class-XI Myosins in Arabidopsis. AB - Arabidopsis possesses 13 genes encoding class-XI myosins. Among these, myosin XI I is phylogenetically distant. To examine the molecular properties of Arabidopsis thaliana myosin XI-I (At myosin XI-I), we performed in vitro mechanical and enzymatic analyses using recombinant constructs of At myosin XI-I. Unlike other biochemically studied class-XI myosins, At myosin XI-I showed extremely low actin activated ATPase activity (Vmax = 3.7 Pi s(-1) head(-1)). The actin-sliding velocity of At myosin XI-I was 0.25 um s(-1), >10 times lower than those of other class-XI myosins. The ADP dissociation rate from acto-At myosin XI-I was 17 s( 1), accounting for the low actin-sliding velocity. In contrast, the apparent affinity for actin in the presence of ATP, estimated from Kapp (0.61 uM) of actin activated ATPase, was extremely high. The equilibrium dissociation constant for actin was very low in both the presence and absence of ATP, indicating a high affinity for actin. To examine At myosin XI-I motility in vivo, green fluorescent protein-fused full-length At myosin XI-I was expressed in cultured Arabidopsis cells. At myosin XI-I localized not only on the nuclear envelope but also on small dots moving slowly (0.23 um s(-1)) along actin filaments. Our results show that the properties of At myosin XI-I differ from those of other Arabidopsis class-XI myosins. The data suggest that At myosin XI-I does not function as a driving force for cytoplasmic streaming but regulates the organelle velocity, supports processive organelle movement or acts as a tension generator. PMID- 27273582 TI - Multi-modal MRI classifiers identify excessive alcohol consumption and treatment effects in the brain. AB - Robust neuroimaging markers of neuropsychiatric disorders have proven difficult to obtain. In alcohol use disorders, profound brain structural deficits can be found in severe alcoholic patients, but the heterogeneity of unimodal MRI measurements has so far precluded the identification of selective biomarkers, especially for early diagnosis. In the present work we used a combination of multiple MRI modalities to provide comprehensive and insightful descriptions of brain tissue microstructure. We performed a longitudinal experiment using Marchigian-Sardinian (msP) rats, an established model of chronic excessive alcohol consumption, and acquired multi-modal images before and after 1 month of alcohol consumption (6.8 +/- 1.4 g/kg/day, mean +/- SD), as well as after 1 week of abstinence with or without concomitant treatment with the antirelapse opioid antagonist naltrexone (2.5 mg/kg/day). We found remarkable sensitivity and selectivity to accurately classify brains affected by alcohol even after the relative short exposure period. One month drinking was enough to imprint a highly specific signature of alcohol consumption. Brain alterations were regionally specific and affected both gray and white matter and persisted into the early abstinence state without any detectable recovery. Interestingly, naltrexone treatment during early abstinence resulted in subtle brain changes that could be distinguished from non-treated abstinent brains, suggesting the existence of an intermediate state associated with brain recovery from alcohol exposure induced by medication. The presented framework is a promising tool for the development of biomarkers for clinical diagnosis of alcohol use disorders, with capacity to further inform about its progression and response to treatment. PMID- 27273581 TI - Contribution of PsbS Function and Stomatal Conductance to Foliar Temperature in Higher Plants. AB - Natural capacity has evolved in higher plants to absorb and harness excessive light energy. In basic models, the majority of absorbed photon energy is radiated back as fluorescence and heat. For years the proton sensor protein PsbS was considered to play a critical role in non-photochemical quenching (NPQ) of light absorbed by PSII antennae and in its dissipation as heat. However, the significance of PsbS in regulating heat emission from a whole leaf has never been verified before by direct measurement of foliar temperature under changing light intensity. To test its validity, we here investigated the foliar temperature changes on increasing and decreasing light intensity conditions (foliar temperature dynamics) using a high resolution thermal camera and a powerful adjustable light-emitting diode (LED) light source. First, we showed that light dependent foliar temperature dynamics is correlated with Chl content in leaves of various plant species. Secondly, we compared the foliar temperature dynamics in Arabidopsis thaliana wild type, the PsbS null mutant npq4-1 and a PsbS overexpressing transgenic line under different transpiration conditions with or without a photosynthesis inhibitor. We found no direct correlations between the NPQ level and the foliar temperature dynamics. Rather, differences in foliar temperature dynamics are primarily affected by stomatal aperture, and rapid foliar temperature increase during irradiation depends on the water status of the leaf. We conclude that PsbS is not directly involved in regulation of foliar temperature dynamics during excessive light energy episodes. PMID- 27273583 TI - Thermally Induced Carbohydroxylation of Styrenes with Aryldiazonium Salts. AB - The radical carbohydroxylation of styrenes with aryldiazonium salts has been achieved under mild thermal conditions. A broad range of aryldiazonium salts was tolerated, and the reaction principle based on a radical-polar crossover mechanism could be extended to carboetherification as well as to a two-step, metal-free variant of the Meerwein arylation leading to stilbenes. PMID- 27273584 TI - Mercury species induced frequency-shift of molecular orientational transformation based on SERS. AB - We proposed a novel readout method based on a peculiar phenomenon in which the vibrational frequencies of a SERS-active probe (dimethyldithiocarbamic acid sodium salt, DASS) can be affected when there is mercury species. Compared to the SERS intensity-dependent quantitative determination method, SERS frequency-shift based methods have several advantages: smaller standard deviation, perfect linear relationship, and higher accuracy and sensitivity. In addition, the SERS frequency-shift-based method was not affected by irreproducible aggregation of the SERS substrate and instrumental factors, which greatly improved the application prospect of SERS-based detection. The DASS-modified silver nanoparticles produced a highly sensitive sensor specific to mercury species. Upon the addition of a solution of mercury species to the chip, the mercury species specifically binds to the sulfur atoms, which induces a frequency shift of the band at 1374 cm(-1). The detection limit of the proposed method for Hg(2+) is as low as 10(-8) M. In addition, the proposed method exhibited the same phenomenon for organic mercury. Moreover, these results suggest that the proposed platform possesses the potential for sensitive, selective, and high-throughput on site mercury pollution monitoring in resource-constrained settings. PMID- 27273586 TI - Information content and acoustic structure of male African elephant social rumbles. AB - Until recently, the prevailing theory about male African elephants (Loxodonta africana) was that, once adult and sexually mature, males are solitary and targeted only at finding estrous females. While this is true during the state of 'musth' (a condition characterized by aggressive behavior and elevated androgen levels), 'non-musth' males exhibit a social system seemingly based on companionship, dominance and established hierarchies. Research on elephant vocal communication has so far focused on females, and very little is known about the acoustic structure and the information content of male vocalizations. Using the source and filter theory approach, we analyzed social rumbles of 10 male African elephants. Our results reveal that male rumbles encode information about individuality and maturity (age and size), with formant frequencies and absolute fundamental frequency values having the most informative power. This first comprehensive study on male elephant vocalizations gives important indications on their potential functional relevance for male-male and male-female communication. Our results suggest that, similar to the highly social females, future research on male elephant vocal behavior will reveal a complex communication system in which social knowledge, companionship, hierarchy, reproductive competition and the need to communicate over long distances play key roles. PMID- 27273588 TI - Current treatment of lacrimal gland carcinoma. AB - PURPOSE OF REVIEW: The traditional treatment for lacrimal gland carcinoma is orbital exenteration followed by radiation therapy. However, orbital exenteration does not prevent distant relapse and death, and some patients experience local regional recurrence after exenteration. More recently, eye-sparing surgery and adjuvant radiation therapy and chemotherapy have gained popularity in the treatment of lacrimal gland carcinoma. Preliminary studies show that these approaches are associated with reasonable local control rates and ocular toxicity profiles. In this review, we discuss recent studies of treatment of lacrimal gland carcinoma, including studies of potential molecular treatment targets. RECENT FINDINGS: Recent studies suggest promising results for neoadjuvant intra arterial chemotherapy followed by orbital exenteration and adjuvant intravenous chemotherapy, but only in patients with an 'intact lacrimal artery'. Recent studies of globe-sparing surgery followed by adjuvant proton radiation therapy or concurrent chemoradiation suggest good local control, reasonable rates of eye preservation, and low risk of serious ocular toxic effects. Larger tumor size and predominant basaloid histology seem to be associated with higher risk of local regional recurrence and distant metastasis. One study showed oncogenic mutations in more than half of cases of lacrimal gland adenoid cystic carcinoma, with KRAS mutations in 10 of 24 patients, suggesting potential benefit of treatments targeting the EGFR-RAS-RAF cascade. SUMMARY: In selected patients with lacrimal gland carcinoma, eye-sparing surgery with eye-sparing radiation therapy offers preservation of visual function with good local control and minimal radiation induced ocular toxic effects. In patients with recurrent or metastatic disease, a search for actionable cancer-associated mutations may be prudent. PMID- 27273587 TI - Toll-like receptor-2 exacerbates murine acute viral hepatitis. AB - Viral replication in the liver is generally detected by cellular endosomal Toll like receptors (TLRs) and cytosolic helicase sensors that trigger antiviral inflammatory responses. Recent evidence suggests that surface TLR2 may also contribute to viral detection through recognition of viral coat proteins but its role in the outcome of acute viral infection remains elusive. In this study, we examined in vivo the role of TLR2 in acute infections induced by the highly hepatotrophic mouse hepatitis virus (MHV) type 3 and weakly hepatotrophic MHV-A59 serotype. To address this, C57BL/6 (wild-type; WT) and TLR2 knockout (KO) groups of mice were intraperitoneally infected with MHV3 or MHV-A59. MHV3 infection provoked a fulminant hepatitis in WT mice, characterized by early mortality and high alanine and aspartate transaminase levels, histopathological lesions and viral replication whereas infection of TLR2 KO mice was markedly less severe. MHV A59 provoked a comparable mild and subclinical hepatitis in WT and TLR2 KO mice. MHV3-induced fulminant hepatitis in WT mice correlated with higher hepatic expression of interferon-beta, interleukin-6, tumour necrosis factor-alpha, CXCL1, CCL2, CXCL10 and alarmin (interleukin-33) than in MHV-A59-infected WT mice and in MHV3-infected TLR2 KO mice. Intrahepatic recruited neutrophils, natural killer cells, natural killer T cells or macrophages rapidly decreased in MHV3 infected WT mice whereas they were sustained in MHV-A59-infected WT mice and MHV3 infected TLR2 KO. MHV3 in vitro infection of macrophagic cells induced rapid and higher viral replication and/or interleukin-6 induction in comparison to MHV-A59, and depended on viral activation of TLR2 and p38 mitogen-activated protein kinase. Taken together, these results support a new aggravating inflammatory role for TLR2 in MHV3-induced acute fulminant hepatitis. PMID- 27273590 TI - The Wnt pathway: a key network in cell signalling dysregulated by viruses. AB - Viruses are obligate parasites dependent on host cells for survival. Viral infection of a cell activates a panel of pattern recognition receptors that mediate antiviral host responses to inhibit viral replication and dissemination. Viruses have evolved mechanisms to evade and subvert this antiviral host response, including encoding proteins that hijack, mimic and/or manipulate cellular processes such as the cell cycle, DNA damage repair, cellular metabolism and the host immune response. Currently, there is an increasing interest whether viral modulation of these cellular processes, including the cell cycle, contributes to cancer development. One cellular pathway related to cell cycle signalling is the Wnt pathway. This review focuses on the modulation of this pathway by human viruses, known to cause (or associated with) cancer development. The main mechanisms where viruses interact with the Wnt pathway appear to be through (i) epigenetic modification of Wnt genes; (ii) cellular or viral miRNAs targeting Wnt genes; (iii) altering specific Wnt pathway members, often leading to (iv) nuclear translocation of beta-catenin and activation of Wnt signalling. Given that diverse viruses affect this signalling pathway, modulating Wnt signalling could be a generalised critical process for the initiation or maintenance of viral pathogenesis, with resultant dysregulation contributing to virus-induced cancers. Further study of this virus-host interaction may identify options for targeted therapy against Wnt signalling molecules as a means to reduce virus-induced pathogenesis and the downstream consequences of infection. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273589 TI - Common UCP2 variants contribute to serum urate concentrations and the risk of hyperuricemia. AB - Elevated serum urate, which is regulated at multiple levels including genetic variants, is a risk factor for gout and other metabolic diseases. This study aimed to investigate the association between UCP2 variants and serum urate as well as hyperuricemia in a Chinese population. In total, 4332 individuals were genotyped for two common UCP2 variants, -866G/A and Ala55Val. These loci were not associated either serum urate level or with a risk of hyperuricemia in the total group of subjects. However, in females, -866G/A and Ala55Val were associated with a lower serum urate (P = 0.006 and 0.014, seperately) and played a protective role against hyperuricemia (OR = 0.80, P = 0.018; OR = 0.79, P = 0.016). These associations were not observed in the males. After further stratification, the two loci were associated with serum urate in overweight, but not underweight females. The haplotype A-T (-866G/A-Ala55Val) was a protective factor for hyperuricemia in the female subgroup (OR = 0.80, P = 0.017). This present study identified a novel gene, UCP2, that influences the serum urate concentration and the risk of hyperuricemia, and the degree of association varies with gender and BMI levels. PMID- 27273591 TI - Evaluation of Retinal Circulation Using Segmental-Scanning Doppler Optical Coherence Tomography in Anesthetized Cats. AB - PURPOSE: To study retinal blood flow (RBF) measurement reproducibility using segmental-scanning Doppler optical coherence tomography (DOCT) in vitro in glass capillaries and in vivo in anesthetized cats. METHODS: As a preliminary study, the flow rates of human blood through glass capillaries were changed by using an infusion pump and measured at 13 preset velocities by DOCT. For in vivo measurement, the cats were anesthetized using sevoflurane. The flow in the parent vessel was compared with the sum of the flow values in the two daughter vessels. The RBF was measured using two different instruments: bidirectional laser Doppler velocimetry (LDV) and DOCT. The reproducibility of the measurements was assessed by calculating the coefficients of variation (CVs) for repeated measurements of RBF at the superior retinal arterioles and venules. RESULTS: In vitro, the flow velocities measured by DOCT agreed well with the preset velocities. In vivo, the flow in the parent vessel agreed with the sum of the flow values in the two daughter vessels. In addition, there were no significant differences in the mean averaged CVs of the RBF in both the arterioles and venules between LDV and DOCT. CONCLUSIONS: The newly developed segmental-scanning DOCT revealed the accuracy of the measurement in in vitro glass capillaries and reproducibility of the measurements of blood velocity in both the retinal arterioles and venules in anesthetized cats. PMID- 27273593 TI - Involvement of IL-37 in the Pathogenesis of Proliferative Diabetic Retinopathy. AB - PURPOSE: Interleukin-37 is suggested as a novel proangiogenic factor in our previous study. In this study, the role of IL-37 was investigated in proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluids from 10 patients with PDR and 8 controls were collected. The levels of IL-37 were determined by ELISA and the relationship between IL-37 and VEGF-A/Ang-2 was analyzed. The effects of IL-37 on chorioretinal endothelial cell (RF/6A) proliferation, migration, and tube formation were determined by BrdU incorporation assay, Boyden chamber assay, scratch-wound assay and tube formation assay. RESULTS: The concentration of IL-37 in the PDR group was 95.09 +/- 5.22 pg/mL and 34.91 +/- 5.61 pg/mL in control group (P = 0.001). The level of IL-37 was highly related to the level of Ang-2 (P = 0.009, r = 0.772) and VEGF-A (P = 0.003, r = 0.827) in the PDR group, and VEGF expression in RF/6A cell was upregulated by IL-37 at low concentration. Interleukin-37 remarkably promoted RF/6A cell proliferation and migration. Interleukin-37 (1 ng/mL) remarkably stimulated tube formation with an increase of 85.3% for total tubule length and 74.1% for branching points compared with PBS control. CONCLUSIONS: The level of IL-37 is elevated in vitreous fluids of patients with PDR and correlates with the level of VEGF-A and Ang-2. Interleukin-37 stimulates proangiogenic response of retinal endothelial cells in vitro, suggesting the involvement of IL-37 in the pathogenesis of PDR. PMID- 27273592 TI - Mutation of wrb, a Component of the Guided Entry of Tail-Anchored Protein Pathway, Disrupts Photoreceptor Synapse Structure and Function. AB - PURPOSE: Tail-anchored (TA) proteins contain a single hydrophobic domain at the C terminus and are posttranslationally inserted into the ER membrane via the GET (guided entry of tail-anchored proteins) pathway. The role of the GET pathway in photoreceptors is unexplored. The goal of this study was to characterize the zebrafish pinball wizard mutant, which disrupts Wrb, a core component of the GET pathway. METHODS: Electroretinography, optokinetic response measurements (OKR), immunohistochemistry, and electron microscopy analyses were employed to assess ribbon synapse function, protein expression, and ultrastructure in 5-day-old zebrafish larvae. Expression of wrb was investigated with real-time qRT-PCR and in situ hybridization. RESULTS: Mutation of wrb abolished the OKR and greatly diminished the ERG b-wave, but not the a-wave. Ribeye and SV2 were partially mislocalized in both photoreceptors and hair cells of wrb mutants. Fewer contacts were seen between photoreceptors and bipolar cells in wrb-/- mutants. Expression of wrb was observed throughout the nervous system and Wrb localized to the ER and synaptic region of photoreceptors. Morpholino knockdown of the cytosolic ATPase trc40, which targets TA proteins to the ER, also diminished the OKR. Overexpression of wrb fully restored contrast sensitivity in mutants, while overexpression of mutant wrbR73A, which cannot bind Trc40, did not. CONCLUSIONS: Proteins Wrb and Trc40 are required for synaptic transmission between photoreceptors and bipolar cells, indicating that TA protein insertion by the TRC pathway is a critical step in ribbon synapse assembly and function. PMID- 27273594 TI - Comments on Macular Choroidal Thickness in Children: The Shandong Children Eye Study. PMID- 27273595 TI - Author Response: Comments on Macular Choroidal Thickness in Children: The Shandong Children Eye Study. PMID- 27273596 TI - Impact of Dry Eye Disease on Work Productivity, and Patients' Satisfaction With Over-the-Counter Dry Eye Treatments. AB - PURPOSE: To assess the effect of dry eye disease on work productivity and performance of non-work-related activities, and patients' satisfaction with over the-counter (OTC) dry eye treatments. METHODS: In this prospective, noninterventional, cross-sectional study, conducted at 10 U.S. optometry/ophthalmology practices, 158 symptomatic dry eye patients naive to prescription medication underwent standard dry eye diagnostic tests and completed Work Productivity and Activity Impairment (WPAI) and Ocular Surface Disease Index (OSDI) questionnaires. Use of OTC dry eye medication, and satisfaction with OTC medication and symptom relief were also assessed. RESULTS: On average, dry eye resulted in loss of 0.36% of work time (~5 minutes over 7 days) and ~30% impairment of workplace performance (presenteeism), work productivity, and non job-related activities. Presenteeism and productivity impairment scores showed significant correlation with OSDI total (r = 0.55) and symptom domain (r = 0.50) scores, but not with dry eye clinical signs. Activity impairment score showed stronger correlation with OSDI total (r = 0.61) and symptom domain (r = 0.53) scores than with clinical signs (r <= 0.20). Almost 75% of patients used OTC dry eye medication. Levels of patient satisfaction with OTC medication (64.2%) and symptom relief from OTC (37.3%) were unaffected by administration frequency (>=3 vs. <=2 times daily). CONCLUSIONS: Dry eye causes negligible absenteeism, but markedly reduces workplace and non-job-related performances. Impairment of work performance is more closely linked to dry eye symptoms than to clinical signs. Patients' perceptions of OTC dry eye medication tend to be more positive than their perceptions of symptom relief. PMID- 27273597 TI - Association of Plasma Semaphorin 3A With Phenotypes of Diabetic Retinopathy and Nephropathy. AB - PURPOSE: To investigate whether diabetic retinopathy phenotypes and albuminuria are associated with the overexpression of plasma semaphorin 3A (Sema3A). METHODS: The study group with severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR), the diabetes without diabetic retinopathy group, and the control group without diabetes consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naive diabetic macular edema (DME) and senile cataract surgery, respectively. In all subjects, the plasma Sema3A levels before intravitreal bevacizumab injections or cataract surgery were measured by enzyme linked immunosorbent assay. In the patients with DME, the capillary nonperfusion area (measured by fluorescein angiography), total macular volume (measured by spectral-domain optical coherence tomography), and the urine albumin-to creatinine ratio were determined. RESULTS: Severe NPDR (57 eyes) and PDR groups (51 eyes) both had significantly higher Sema3A levels than the control (58 eyes) and diabetes without diabetic retinopathy groups (54 eyes) (P < 0.001). Moreover, the PDR group had higher Sema3A levels than the severe NPDR group (P < 0.001). Plasma Sema3A levels correlated positively with the retinal nonperfusion area size (r = 0.844, P = 0.004), total macular volume (r = 0.765, P = 0.005), and the urine albumin-to-creatinine ratio (r = 0.752, P < 0.001). When DME patients were divided into normo-, micro-, and macroalbuminuria groups, the macroalbuminuria group had significantly higher plasma Sema3A levels than the microalbuminuria group or the normoalbuminuria group (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: The plasma Sema3A levels correlated significantly with the phenotypes of diabetic retinopathy and albuminuria. This suggests that Sema3A may be a potential biomarker for diabetic retinopathy and nephropathy. PMID- 27273600 TI - Halogen bonding anion recognition. AB - A halogen bond is an attractive non-covalent interaction between an electrophilic region in a covalently bonded halogen atom and a Lewis base. While these interactions have long been exploited as a tool in crystal engineering their powerful ability to direct supramolecular self-assembly and molecular recognition processes in solution has, until recently, been overlooked. During the last decade however an ever-increasing number of studies on solution-phase halogen bond-mediated anion recognition processes has emerged. This Feature Article summarises advancements which have been made thus far in this rapidly developing research area. We survey the use of iodoperfluoroarene, haloimidazolium and halotriazole/triazolium halogen-bond-donor motifs in anion receptor design, before providing an account of our research into the application of mechanically interlocked rotaxane and catenane frameworks as halogen bonding anion host systems. PMID- 27273598 TI - Evaluating Descriptive Metrics of the Human Cone Mosaic. AB - PURPOSE: To evaluate how metrics used to describe the cone mosaic change in response to simulated photoreceptor undersampling (i.e., cell loss or misidentification). METHODS: Using an adaptive optics ophthalmoscope, we acquired images of the cone mosaic from the center of fixation to 10 degrees along the temporal, superior, inferior, and nasal meridians in 20 healthy subjects. Regions of interest (n = 1780) were extracted at regular intervals along each meridian. Cone mosaic geometry was assessed using a variety of metrics - density, density recovery profile distance (DRPD), nearest neighbor distance (NND), intercell distance (ICD), farthest neighbor distance (FND), percentage of six-sided Voronoi cells, nearest neighbor regularity (NNR), number of neighbors regularity (NoNR), and Voronoi cell area regularity (VCAR). The "performance" of each metric was evaluated by determining the level of simulated loss necessary to obtain 80% statistical power. RESULTS: Of the metrics assessed, NND and DRPD were the least sensitive to undersampling, classifying mosaics that lost 50% of their coordinates as indistinguishable from normal. The NoNR was the most sensitive, detecting a significant deviation from normal with only a 10% cell loss. CONCLUSIONS: The robustness of cone spacing metrics makes them unsuitable for reliably detecting small deviations from normal or for tracking small changes in the mosaic over time. In contrast, regularity metrics are more sensitive to diffuse loss and, therefore, better suited for detecting such changes, provided the fraction of misidentified cells is minimal. Combining metrics with a variety of sensitivities may provide a more complete picture of the integrity of the photoreceptor mosaic. PMID- 27273599 TI - Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models. AB - SCOPE: Fish oil-derived long-chain monounsaturated fatty acids (LCMUFA) containing chain lengths longer than 18 were previously shown to improve cardiovascular disease risk factors in mice. However, it is not known if LCMUFA also exerts anti-atherogenic effects. The main objective of the present study was to investigate the effect of LCMUFA on the development of atherosclerosis in mouse models. METHODS AND RESULTS: LDLR-KO mice were fed Western diet supplemented with 2% (w/w) of either LCMUFA concentrate, olive oil, or not (control) for 12 wk. LCMUFA, but not olive oil, significantly suppressed the development of atherosclerotic lesions and several plasma inflammatory cytokine levels, although there were no major differences in plasma lipids between the three groups. At higher doses 5% (w/w) LCMUFA supplementation was observed to reduce pro-atherogenic plasma lipoproteins and to also reduce atherosclerosis in ApoE-KO mice fed a Western diet. RNA sequencing and subsequent qPCR analyses revealed that LCMUFA upregulated PPAR signaling pathways in liver. In cell culture studies, apoB-depleted plasma from LDLR-K mice fed LCMUFA showed greater cholesterol efflux from macrophage-like THP-1 cells and ABCA1-overexpressing BHK cells. CONCLUSION: Our research showed for the first time that LCMUFA consumption protects against diet-induced atherosclerosis, possibly by upregulating the PPAR signaling pathway. PMID- 27273602 TI - Patient Navigation for Comprehensive Cancer Screening in High-Risk Patients Using a Population-Based Health Information Technology System: A Randomized Clinical Trial. AB - IMPORTANCE: Patient navigation (PN) to improve cancer screening in low-income and racial/ethnic minority populations usually focuses on navigating for single cancers in community health center settings. OBJECTIVE: We evaluated PN for breast, cervical, and colorectal cancer screening using a population-based information technology (IT) system within a primary care network. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted from April 2014 to December 2014 in 18 practices in an academic primary care network. All patients eligible and overdue for cancer screening were identified and managed using a population-based IT system. Those at high risk for nonadherence with completing screening were identified using an electronic algorithm (language spoken, number of overdue tests, no-show visit history), and randomized to a PN intervention (n = 792) or usual care (n = 820). Navigators used the IT system to track patients, contact them, and provide intense outreach to help them complete cancer screening. MAIN OUTCOMES AND MEASURES: Mean cancer screening test completion rate over 8-month trial for each eligible patient, with all overdue cancer screening tests combined using linear regression models. Secondary outcomes included the proportion of patients completing any and each overdue cancer screening test. RESULTS: Among 1612 patients (673 men and 975 women; median age, 57 years), baseline patient characteristics were similar among randomized groups. Of 792 intervention patients, patient navigators were unable to reach 151 (19%), deferred 246 (38%) (eg, patient declined, competing comorbidity), and navigated 202 (32%). The mean proportion of patients who were up to date with screening among all overdue screening examinations was higher in the intervention vs the control group for all cancers combined (10.2% vs 6.8%; 95% CI [for the difference], 1.5%-5.2%; P < .001), and for breast (14.7% vs 11.0%; 95% CI, 0.2% 7.3%; P = .04), cervical (11.1% vs 5.7%; 95% CI, 0.8%-5.2%; P = .002), and colon (7.6% vs 4.6%; 95% CI, 0.8%-5.2%; P = .01) cancer compared with control. The proportion of overdue patients who completed any cancer screening during follow up was higher in the intervention group (25.5% vs 17.0%; 95% CI, 4.7%-12.7%; P < .001). The intervention group had more patients completing screening for breast (23.4% vs 16.6%; 95% CI, 1.8%-12.0%; P = .009), cervical (14.4% vs 8.6%; 95% CI, 1.6%-10.5%; P = .007), and colorectal (13.7% vs 7.0%; 95% CI, 3.2%-10.4%; P < .001) cancer. CONCLUSIONS AND RELEVANCE: Patient navigation as part of a population-based IT system significantly increased screening rates for breast, cervical, and colorectal cancer in patients at high risk for nonadherence with testing. Integrating patient navigation into population health management activities for low-income and racial/ethnic minority patients might improve equity of cancer care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02553538. PMID- 27273601 TI - A high-throughput assay for the measurement of uropathogenic Escherichia coli attachment to urinary bladder cells. AB - Strains of uropathogenic Escherichia coli (UPEC) are the major causative agent of urinary tract infections (UTI), the most common infectious diseases in the world. Their ability to attach and enter into cells in the urinary tract is a limiting step for their pathogenicity. Many studies are thus focussing on these key mechanisms to propose new therapeutic strategies. To facilitate such studies, we developed a fast and high-throughput assay which makes it possible to monitor the interaction of UPEC with cultured human uroepithelial cells. This assay allows measurement of the in vitro association of fluorescently labelled clinical isolates with bladder epithelial cells using flow cytometry in a microplate format. The assay was sensitive enough to detect variations between isolates expressing different adhesins and virulence factors and the inhibitory effect of proanthocyanidins. Thus we have developed a fast and robust assay which allows us to measure variations in the adhesion properties of UPEC to human bladder cells. This novel assay will be valuable for the study of initial steps of pathogenesis in UTI and for the screening or validation of inhibitory molecules. PMID- 27273603 TI - The value of flexibility in conservation financing. AB - Land-acquisition strategies employed by conservation organizations vary in their flexibility. Conservation-planning theory largely fails to reflect this by presenting models that are either extremely inflexible-parcel acquisitions are irreversible and budgets are fixed-or extremely flexible-previously acquired parcels can readily be sold. This latter approach, the selling of protected areas, is infeasible or problematic in many situations. We considered the value to conservation organizations of increasing the flexibility of their land acquisition strategies through their approach to financing deals. Specifically, we modeled 2 acquisition-financing methods commonly used by conservation organizations: borrowing and budget carry-over. Using simulated data, we compared results from these models with those from an inflexible fixed-budget model and an extremely flexible selling model in which previous acquisitions could be sold to fund new acquisitions. We then examined 3 case studies of how conservation organizations use borrowing and budget carry-over in practice. Model comparisons showed that borrowing and budget carry-over always returned considerably higher rewards than the fixed-budget model. How they performed relative to the selling model depended on the relative conservation value of past acquisitions. Both the models and case studies showed that incorporating flexibility through borrowing or budget carry-over gives conservation organizations the ability to purchase parcels of higher conservation value than when budgets are fixed without the problems associated with the selling of protected areas. PMID- 27273605 TI - Survey on Current Postnatal Surgical Management of Myelomeningocele in Germany. AB - Background and Study Aims Although postnatal surgery can be regarded as the standard of care for open myelomeningocele (MMC), there is no uniform treatment for this condition in Germany. This study assessed the current situation regarding the management of open MMC, a first and essential step toward the development of standards of practice. Patients and Methods In the second half of 2009, we had sent standardized questionnaires to 139 neurosurgery departments and 73 pediatric surgery departments (number of returned questionnaires: 98 and 62, respectively) to identify the principles of MMC management. Newborns with open MMC are treated in 57 of the neurosurgery departments and in 18 of the pediatric surgery departments. Results Overall, 41 of the 57 neurosurgery departments and 16 of the 18 pediatric surgery departments providing care for newborns with MMC perform MMC closure within 24 hours of delivery. In 52 neurosurgery departments and 15 pediatric surgery departments, infants with spina bifida are delivered by planned cesarean section. The diagnostic investigations performed between the time of caesarean delivery and plastic surgical closure vary from none to magnetic resonance imaging of the spine. The criteria underlying the placement of shunts and the time to plastic surgical closure are highly variable. Conclusions The type of treatment that infants with open MMC receive in Germany differs from institution to institution. Clear and consistent guidelines must be established using an interdisciplinary approach to improve treatment and standardize the care provided by surgical specialists for infants with MMC. PMID- 27273604 TI - Macrophage Migration Inhibitor Factor Upregulates MCP-1 Expression in an Autocrine Manner in Hepatocytes during Acute Mouse Liver Injury. AB - Macrophage migration inhibitor factor (MIF), a multipotent innate immune mediator, is an upstream component of the inflammatory cascade in diseases such as liver disease. Monocyte chemoattractant protein-1 (MCP-1), a highly representative chemokine, is critical in liver disease pathogenesis. We investigated the role of MIF in regulating hepatocytic MCP-1 expression. MIF and MCP-1 expression were characterized by immunochemistry, RT-PCR, ELISA, and immunoblotting in CCl4-treated mouse liver and isolated hepatocytes. MIF was primarily distributed in hepatocytes, and its expression increased upon acute liver injury. Its expression was also increased in injured hepatocytes, induced by LPS or CCl4, which mimic liver injury in vitro. MIF was expressed earlier than MCP-1, strongly inducing hepatocytic MCP-1 expression. Moreover, the increase in MCP-1 expression induced by MIF was inhibited by CD74- or CD44-specific siRNAs and SB203580, a p38 MAPK inhibitor. Further, CD74 or CD44 deficiency effectively inhibited MIF-induced p38 activation. MIF inhibitor ISO-1 reduced MCP-1 expression and p38 phosphorylation in CCl4-treated mouse liver. Our results showed that MIF regulates MCP-1 expression in hepatocytes of injured liver via CD74, CD44, and p38 MAPK in an autocrine manner, providing compelling information on the role of MIF in liver injury, and implying a new regulatory mechanism for liver inflammation. PMID- 27273606 TI - Transcriptomic Signature of the CD24hi CD38hi Transitional B Cells Associated With an Immunoregulatory Phenotype in Renal Transplant Recipients. AB - The role of B cells after transplant regarding allograft rejection or tolerance has become a topic of major interest. Recently, in renal transplant recipients, a B cell signature characterized by the overexpression of CD19+ CD38hi CD24hi transitional B cells has been observed in operationally tolerant patients and in belatacept-treated patients with significantly lower incidence of donor-specific antibodies. The phenotypic and functional characterization of these transitional B cells is far from exhaustive. We present the first transcriptomic and phenotypic analysis associated with this cell phenotype. Three populations were studied and compared: (i) transitional CD24hi CD38hi , (ii) CD24+ CD38- , and (iii) CD24int CD38int B cells. Transcriptome bioinformatic analysis revealed a particular signature for the CD24hi CD38hi population. Phenotypic analysis showed that CD24hi CD38hi transitional B cells also expressed CD9, CD10, CD1b and inducible T cell costimulator ligand (ICOS-L) markers. In addition, we found enrichment of IL-10+ cells among CD24hi CD38hi cells expressing ICOS-L and CD1b, the latter showing regulatory properties. Renal transplant recipients treated with belatacept exhibited significant expression of CD1b. Our results show that transitional CD24hi CD38hi B cells exhibit a distinct and specific profile, and this could be helpful for understanding of immune-regulatory mechanisms and immune monitoring in the field of organ transplant and autoimmune disease. PMID- 27273607 TI - Bisphenol S- and bisphenol A-induced adipogenesis of murine preadipocytes occurs through direct peroxisome proliferator-activated receptor gamma activation. AB - BACKGROUND/OBJECTIVES: The use of bisphenol A (BPA) in consumer products and food packaging has been associated under certain conditions with a risk of negative health outcomes. This prompted its removal from many products and replacement with structural analogs. Bisphenol S (BPS) is one such analog, but its metabolic effects have not been fully characterized. The objective of our study was to determine whether BPS functions similarly to BPA at inducing adipogenesis. METHODS: Murine 3T3-L1 preadipocytes were used to evaluate and compare the adipogenic potential of BPS to BPA. Cells were treated with 0.01-50 MUM BPS or 0.01-50 MUM BPA and adipogenic effects were measured. Further, their ability to activate peroxisome proliferator-activated receptor gamma (PPARgamma), an adipogenic transcription factor, was also determined. RESULTS: Our results indicate that treatment of 3T3-L1 cells with BPS induced lipid accumulation and increased mRNA and protein expression of key adipogenic markers (1-50 MUM; P<0.05). BPS treatment resulted in a higher expression of adipogenic markers as well as greater lipid accumulation when compared with BPA treatment. We showed that BPS can upregulate lipoprotein lipase, adipocyte protein 2, PPARgamma, perilipin, adipsin and CCAAT/enhancer-binding protein alpha mRNA expression levels. Furthermore, using transcriptional assays, we showed that BPS and BPA can modestly activate PPARgamma using a PPRE (PPARgamma response element)-dependent luciferase construct by 1.5-fold (P<0.05). However, BPS but not BPA was able to competitively inhibit rosiglitazone (ROSI)-activated PPARgamma, suggesting that BPS interacts with PPARgamma distinctly from BPA. Co-treatment of cells with the selective PPARgamma antagonist GW9662 inhibits BPS-, BPA-, ROSI- but not dexamethasone-dependent adipogenic differentiation. CONCLUSIONS: Both BPA and BPS can enhance 3T3-L1 adipocyte differentiation in a dose-dependent manner and require PPARgamma to induce adipogenesis. Through direct comparison, we show that BPS is a more potent adipogen than BPA. PMID- 27273608 TI - Brief Report: Anti-Eukaryotic Initiation Factor 2B Autoantibodies Are Associated With Interstitial Lung Disease in Patients With Systemic Sclerosis. AB - OBJECTIVE: To investigate novel systemic sclerosis (SSc) autoantibodies in autoantibody-negative patients and establish clinical associations. METHODS: Serum samples and clinical data for 548 patients with SSc were collected. Routine serologic techniques were used to test the serum samples for known SSc autoantibodies, and samples with negative results were further investigated by radiolabeled-protein immunoprecipitation assay. Sera that immunoprecipitated a novel 30-kd band were analyzed by indirect immunofluorescence and immunoprecipitation, using depleted cell extracts to establish a common reactivity. Mass spectrometry was performed to identify the novel autoantigen, and the results were confirmed using commercial antibodies. Sera from 426 patients with other forms of connective tissue disease, 103 with rheumatoid arthritis, 114 with idiopathic interstitial lung disease (ILD), and 150 healthy subjects were serotyped as controls. RESULTS: A novel autoantigen with a molecular weight of ~30 kd was recognized by 7 sera from patients with SSc, 6 of whom had ILD, and by no controls. Six of the patients had diffuse cutaneous involvement, and 4 had overlap features with other autoimmune diseases. Immunodepletion experiments indicated that all samples targeted the same autoantigen, and mass spectrometry identified the novel autoantigen as eukaryotic initiation factor 2B (eIF2B). CONCLUSION: We report the identification of a novel autoantibody (anti-eIF2B) in a small number of patients with SSc (~1%); this autoantibody is closely associated with diffuse cutaneous manifestations and the presence of ILD. PMID- 27273609 TI - District nurses' perspectives on detecting mental health problems and promoting mental health among community-dwelling seniors with multimorbidity. AB - AIMS AND OBJECTIVES: To describe district nurses' perspectives on detecting mental health problems and promoting mental health among homebound older people with multimorbidity. BACKGROUND: Mental health problems among older people with multiple chronic conditions, that is, multimorbidity, are challenging issues. These patients' homes often serve as arenas in which district nurses can promote health. Mental health promotion must be studied in greater depth within primary care because older people with multimorbidity are particularly prone to developing poor mental health, which can go undetected and untreated. DESIGN: A descriptive, qualitative study using semi-structured interviews and content analysis. METHODS: Twenty-five district nurses completed individual or focus group interviews. Data were analysed using qualitative content analysis. RESULTS: Most district nurses stated that detecting mental health problems and promoting mental health were important tasks but that they typically focused on more practical home health care tasks. The findings revealed that district nurses focused on assessment, collaboration and social support as means of detecting mental health problems and promoting mental health. CONCLUSIONS: The district nurses described various factors and actions that appeared to be important prerequisites for their involvement in primary mental health care. Nevertheless, there were no established goals for mental health promotion, and district nurses often seemed to depend on their collaboration with other actors. Our findings indicated that district nurses cannot bear the primary responsibility for the early detection of mental health problems and early interventions to promote mental health within this population. RELEVANCE TO CLINICAL PRACTICE: The findings of this study indicated that workforce training and collaboration between different care providers are important elements in the future development of this field. Early detection and early treatment of mental health-related issues should also be stated as explicit objectives in the provision of care to community-dwelling older people with multimorbidity. PMID- 27273610 TI - The concurrent and longitudinal associations of temperament and nutritional risk factors in early childhood. AB - BACKGROUND: Early childhood temperament is increasingly recognized as an important attribute that may impact screen time use, outdoor play and childhood obesity. The relationship between temperament and nutrition in preschool children is less clear. OBJECTIVE: The objective of the study is to investigate if temperament dimensions (negative affectivity, effortful control and surgency) in early childhood are associated with nutritional risk factors. METHODS: Six hundred seventy-eight children were followed (mean age at baseline visit 3.1 years; mean time to follow-up 16.5 months). Parents reported on child temperament and nutritional risk factors during regularly scheduled well-child clinic visits. RESULTS: A mixed effect model demonstrated a significant association between higher negative affectivity (1.03; 95% CI 0.69 to 1.37) and higher effortful control (-0.88; 95% CI -1.27 to -0.49) on concurrent nutritional risk, independent of covariates. Multivariate linear regression analysis identified that higher effortful control, and not negative affectivity, was significantly associated with a decrease in nutritional risk (-0.67; 95% CI -1.10 to -0.24) over time, independent of covariates. There was no relationship identified between surgency and nutritional risk. CONCLUSION: Three-year-old children with higher effortful control had reduced nutritional risk at 5 years of age. Future nutritional risk prevention strategies may benefit from interventions to increase effortful control in early childhood. PMID- 27273611 TI - Syntheses, characterization and electrochemical and spectroscopic properties of ruthenium-iron complexes of 2,3,5,6-tetrakis(2-pyridyl)pyrazine and ferrocene acetylide ligands. AB - Heterodimetallic Ru-Fe complexes [(tppz)(PPh3)2RuL](ClO4) (L = C[triple bond, length as m-dash]CFc, [](ClO4); C[triple bond, length as m-dash]C-C6H4-C[triple bond, length as m-dash]CFc), [](ClO4); C[triple bond, length as m-dash]C-C6H4 C6H4-C[triple bond, length as m-dash]CFc, [](ClO4)) were synthesized by the reactions of [(tppz)(PPh3)2RuCl](ClO4) (tppz = 2,3,5,6-tetrakis(2 pyridyl)pyrazine) with ferrocence-acetylide ligands and characterized by ESI-MS, and (1)H and (31)P NMR spectroscopies. The structure of [](PF6) was determined by X-ray crystallography. The electrochemical studies show that compounds [](ClO4) [](ClO4) possess two widely separated anodic peaks, ascribable to one-electron oxidation of Fc and Ru(II), respectively. This assignment is further corroborated by the results of UV-vis-NIR, XPS, and theoretical calculation studies. Compound [](ClO4) exhibits significant RuFe metal-metal interactions across the Ru C[triple bond, length as m-dash]C-Fc backbone. As revealed by electrochemical, spectroscopic and theoretical computational studies, one-electron oxidized species [](ClO4)2 is between the electronically delocalized and valence-trapped state and shows a typical Robin-Day class II mixed-valence behavior. PMID- 27273612 TI - Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder. AB - OBJECTIVE: The objective of the study was to investigate the relationship between structural connectivity (SC) and functional connectivity (FC) in the cingulum in bipolar disorder (BD) and its various phases. METHOD: We combined resting-state functional magnetic resonance imaging and probabilistic tractographic diffusion tensor imaging to investigate FC and SC of the cingulum and its portions, the SC FC relationship, and their correlations with clinical and neurocognitive measures on sustained attention in manic (n = 21), depressed (n = 20), and euthymic (n = 20) bipolar patients and healthy controls (HC) (n = 42). RESULTS: First, we found decreased FC between the anterior and posterior parts of the cingulum in manic patients when compared to depressed patients and HC. Second, we observed decreased SC of the cingulum bundle, particularly in its anterior part, in manic patients when compared to HC. Finally, alterations in the cingulum FC (but not SC) correlated with clinical severity scores while changes in the cingulum SC (but not FC) were related with neurocognitive deficits in sustained attention in BD. CONCLUSION: We demonstrate for the first time a reduction in FC and concomitantly in SC of the cingulum in mania, which correlated with psychopathological and neurocognitive parameters, respectively, in BD. This supports the central role of cingulum connectivity specifically in mania. PMID- 27273613 TI - Telemedicine in the UK Defence Medical Services: time for an upgrade? PMID- 27273614 TI - What are the best and worst things about having a father in UK Armed Forces? Analysis of free text responses. AB - OBJECTIVE: This study aims to explore what adolescents report as the best and worst aspects of having a father in the UK military. METHODS: Qualitative data were collected from 171 adolescents aged 11-16 years, via an online questionnaire exploring the impact of paternal military service on childhood well-being (response rate=70%). Questions about the best and worst aspects of their father's military role were examined. Content analysis has been used to code the qualitative data into themes. RESULTS: 85 girls and 86 boys were included with a mean age of 13 years (SD 1.92). The results showed lack of contact as the single most commonly reported negative factor of having a father in the military (61%). Positive aspects of their fathers' job most frequently reported included a sense of pride (25%) and financial benefits (25%). CONCLUSIONS: Adolescents take a great deal of pride in their father's jobs in the military, and they enjoy the financial benefits. A majority, however, feel a lack of contact with their father is the most negative factor. PMID- 27273615 TI - The success of battlefield surgical airway insertion in severely injured military patients: a UK perspective. AB - BACKGROUND: The insertion of a surgical airway in the presence of severe airway compromise is an uncommon occurrence in everyday civilian practice. In conflict, the requirement for insertion of a surgical airway is more common. Recent military operations in Afghanistan resulted in large numbers of severely injured patients, and a significant proportion required definitive airway management through the insertion of a surgical airway. OBJECTIVE: To examine the procedural success and survival rate to discharge from a military hospital over an 8-year period. METHODS: A retrospective database and chart review was conducted, using the UK Joint Theatre Trauma Registry and the Central Health Records Library. Patients who underwent surgical airway insertion by UK medical personnel from 2006 to 2014 were included. Procedural success, demographics, Injury Severity Score, practitioner experience and patient survival data were collected. Descriptive statistics were used for data comparison, and statistical significance was defined as p<0.05. RESULTS: 86 patients met the inclusion criterion and were included in the final analysis. The mean patient age was 25 years, (SD 5), with a median ISS of 62.5 (IQR 42). 79 (92%) of all surgical airways were successfully inserted. 7 (8%) were either inserted incorrectly or failed to perform adequately. 80 (93%) of these procedures were performed either by combat medical technicians or General Duties Medical Officers (GDMOs) at the point of wounding or Role 1. 6 (7%) were performed by the Medical Emergency Response Team. 21 (24%) patients survived to hospital discharge. DISCUSSION: Surgical airways can be successfully performed in the most hostile of environments with high success rates by combat medical technicians and GDMOs. These results compare favourably with US military data published from the same conflict. PMID- 27273616 TI - Dicer functions as an antiviral system against human adenoviruses via cleavage of adenovirus-encoded noncoding RNA. AB - In various organisms, including nematodes and plants, RNA interference (RNAi) is a defense system against virus infection; however, it is unclear whether RNAi functions as an antivirus system in mammalian cells. Rather, a number of DNA viruses, including herpesviruses, utilize post-transcriptional silencing systems for their survival. Here we show that Dicer efficiently suppresses the replication of adenovirus (Ad) via cleavage of Ad-encoding small RNAs (VA-RNAs), which efficiently promote Ad replication via the inhibition of eIF2alpha phosphorylation, to viral microRNAs (mivaRNAs). The Dicer knockdown significantly increases the copy numbers of VA-RNAs, leading to the efficient inhibition of eIF2alpha phosphorylation and the subsequent promotion of Ad replication. Conversely, overexpression of Dicer significantly inhibits Ad replication. Transfection with mivaRNA does not affect eIF2alpha phosphorylation or Ad replication. These results indicate that Dicer-mediated processing of VA-RNAs leads to loss of activity of VA-RNAs for enhancement of Ad replication and that Dicer functions as a defence system against Ad in mammalian cells. PMID- 27273617 TI - Asterionellopsis tropicalis (Bacillariophyceae): a new tropical species found in diatom accumulations. AB - The diatom Asterionellopsis glacialis sensu lato forms high-density patches in the surf zone of some sandy beaches worldwide and was until recently considered a cosmopolitan species. With the recent description of four cryptic species, the identity of specimens found in these accumulations remains uncertain. In this study, diatom patches were sampled from two sandy beaches of the Brazilian coast: one tropical (Futuro Beach, 3 degrees S; 38 degrees W) and one subtropical (Cassino Beach, 32 degrees S; 52 degrees W). Fine structure of frustules and the sequencing of three phylogenetic markers revealed the subtropical strains to be A. guyunusae and the tropical strains to be a new species, here described as Asterionellopsis tropicalis sp. nov. A. tropicalis was differentiated morphologically by the number of striae in 10 MUm at the foot pole and head (39 44; 38-45, respectively), from A. lenisilicea (46-55; 46-64), A. maritima (46-51; 46-60), and A. thurstonii (42-58; 55-70). The number of striae at the head region of the valvocopula (10 MUm) helped to distinguish A. tropicalis (56-62) from A. guyunusae (61-64), but A. tropicalis was morphologically undistinguishable from A. glacialis. The sequence divergence from other identified Asterionellopsis species was 13%-16% (Cox1), 11%-12% (5.8S + ITS2) and 2%-6% (RbcL), and A. tropicalis formed a distinct monophyletic clade with high support in all analyzed phylogenetic trees (single or multi-locus). This work will aid in the understanding of the ecological and physiological diversity of diatom patches that are key to the trophic webs of sandy beaches. PMID- 27273618 TI - Serum stress responsive gene EhslncRNA of Entamoeba histolytica is a novel long noncoding RNA. AB - Non coding RNAs are known to play important roles in regulating gene expression at the transcriptional and posttranscriptional levels in metazoans. There is very little information available about non coding RNAs in protists such as Entamoeba histolytica. Antisense and micro RNAs have been reported in E. histolytica, however no long non coding RNAs has been reported yet. Here, we report our findings on an in vitro serum stress-inducible gene EhslncRNA, a member of B1 transmembrane kinase family of E. histolytica. EhslncRNA encodes a transcript of 2.6 kb and sequence analysis revealed that there is no ORF >150 bp within this transcript. The transcript was found to be polyadenylated and mainly associated with monosomes in the cytoplasm under serum starvation. In normal proliferating cells this RNA is mainly present in the nucleus. The promoter element was mapped between 437 to 346 nucleotides upstream of transcriptional start site and has both positive and negative regulatory elements. Deletion of the negative element converted the promoter to serum inducible type. Oxygen and heat stress also increased expression levels of EhslncRNA. These observations suggest that EhslncRNA may be a long non coding RNA and likely to help cells withstand stressful conditions in the host. PMID- 27273620 TI - Needs assessment for collaborative network in pediatric clinical research and education. AB - BACKGROUND: A collaborative network for pediatric research has not been fully established in Japan. To identify the network infrastructure, we conducted a survey on the support and education for clinical research currently available in children's hospitals. METHODS: In November 2014, a 27-question survey was distributed to 31 hospitals belonging to the Japanese Association of Children's Hospitals and Related Institutions (JACHRI) to assess clinical research support, research education, research achievements, and their expectations. RESULTS: All the hospitals responded to the survey. Overall, 74.2% of hospitals had clinical research support divisions. Although all hospitals had ethics committees, <30% of the hospitals had a data manager, intellectual property management unit, biostatistician, and English-language editor. Seven hospitals had education programs for clinical research. The number of seminars and workshops for clinical research had significant correlations with the number of physicians (r = 0.927), pediatricians (r = 0.922), and clinical trial management physicians (r = 0.962). There was a significant difference in the number of clinical trials initiated by physicians between hospitals with research education programs and those without (P < 0.01). The number of education programs was significantly correlated with the number of original articles and case reports in English (r = 0.788), and the number of publications in Japanese (r = 0.648). All hospitals recognized the need for a leader to establish a collaborative network for clinical research. CONCLUSIONS: Important factors for creating a collaborative system for pediatric research in Japan were identified. Human resources to support clinical research are a key factor to improve clinical research education and research achievements. PMID- 27273619 TI - Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy. AB - Intravesical instillation of Bacillus Calmette-Guerin is currently used as adjuvant therapy for superficial, non-muscle invasive bladder cancer (NMIBC). However, nearly 40% of patients with NMIBC will fail Bacillus Calmette-Guerin therapy. In an attempt to investigate the feasibility of using insect baculovirus based vectors for bladder cancer therapy, we observed that intravesical instillation of baculoviruses without transgene up-regulated a set of Th1-type of cytokines and increased the survival rate of mice bearing established orthotopic bladder tumors. When baculoviral vectors were used to co-deliver the mouse CD40 ligand and IL-15 genes through intravesical instillation, the immunogene therapy triggered significantly increased bladder infiltrations of inflammatory monocytes, CD4(+), CD8(+) and gammadelta T lymphocytes. All treated animals survived beyond 12 months whereas control animals died around 2 months after tumor inoculation. We conclude that direct intravesical instillation of baculoviral gene transfer vectors holds the potential to be a novel therapeutic modality for NMIBC. PMID- 27273621 TI - A Robust Metal-Organic Framework for Dynamic Light-Induced Swing Adsorption of Carbon Dioxide. AB - Adsorbents for CO2 capture need to demonstrate efficient release. Light-induced swing adsorption (LISA) is an attractive new method to release captured CO2 that utilizes solar energy rather than electricity. MOFs, which can be tailored for use in LISA owing to their chemical functionality, are often unstable in moist atmospheres, precluding their use. A MOF is used that can release large quantities of CO2 via LISA and is resistant to moisture across a large pH range. PCN-250 undergoes LISA, with UV flux regulating the CO2 desorption capacity. Furthermore, under UV light, the azo residues within PCN-250 have constrained, local, structural flexibility. This is dynamic, rapidly switching back to the native state. Reusability tests demonstrate a 7.3 % and 4.9 % loss in both adsorption and LISA capacity after exposure to water for five cycles. These minimal changes confirm the structural robustness of PCN-250 and its great potential for triggered release applications. PMID- 27273622 TI - Asymmetric plasmonic induced ionic noise in metallic nanopores. AB - We present distinct asymmetric plasmon-induced noise properties of ionic transport observed through gold coated nanopores. We thoroughly investigated the effects of bias voltage and laser illumination. We show that the potential drop across top-coated silicon nanocavity pores can give rise to a large noise asymmetry (~2-3 orders of magnitude). Varying the bias voltage has an appreciable effect on the noise density spectra, typically in the Lorentzian components. The laser power is found to strongly affect the ionic noise level as well as the voltage threshold for light-induced noise generation. The asymmetric noise phenomenon is attributed to plasmon-induced interfacial reactions which promote light-induced charge fluctuation in the ion flow and allow voltage modulation of photo-induced carriers surmounting over such Schottky junctions. We further compare the ionic noise performances of gold nanocavities containing different material stacks, among which thermal oxide passivation of the silicon successfully mitigates the light-induced noise and is also fully CMOS-compatible. The understanding of the described noise characteristics will help to foster multiple applications using related structures including plasmonic-based sensing or plasmon-induced catalysis such as water splitting or solar energy conversion devices. PMID- 27273623 TI - Aiming low: A resident male's rank predicts takeover success by challenging males in Yunnan snub-nosed monkeys. AB - In many primate species that form one-male breeding units (OMUs), the threat of a takeover by a bachelor male represents a major challenge to group stability and individual reproductive success. In the case of snub-nosed monkeys, which live in large multilevel or modular societies (MLS) comprising several OMUs that travel, feed and rest together and as well as one or more all male units (AMUs), the process by which rival males challenge resident OMU males for access to females is poorly understood. From September 2012 to October 2013, we recorded 48 cases in which rival males visited an OMU in a MLS of Yunnan snub-nosed monkeys (Rhinopithecus bieti) inhabiting the Baimaxueshan National Nature Reserve, Yunnan Province, China. In 40 cases, rival males engaged in mild agonistic interactions (approaching, staring, teeth-baring and chasing) but failed to take over the group; we counted these visits as failed takeovers, recognizing that they may nevertheless allow rival males to assess the competitive ability of residents. During eight successful takeovers, however, there was severe physical aggression between challenging and resident males, with serious injuries to participants. We found that neither the number of adult and subadult females in an OMU, the number of non-pregnant, non-lactating adult females in an OMU, nor the rank of a resident male relative to other resident males in the MLS predicted which OMU a challenging male targeted for takeover. However, a resident male's rank significantly predicted whether takeover attempts were successful. Specifically, challenging males were more successful in displacing a lower-ranking resident male than a higher-ranking male. Given that a Yunnan snub-nosed monkey MLS may contain as many as 40 resident and 36 bachelor males, continued research is required to determine the set of factors that enable resident males to maintain high social rank and successfully defend their harems. Am. J. Primatol. 78:974 982, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273625 TI - Arrhythmia associated with buprenorphine and methadone reported to the Food and Drug Administration. PMID- 27273624 TI - Soluble B7-H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NF-kappaB pathway. AB - Many studies have demonstrated a relationship between soluble B7-H3 (sB7-H3) and the poor prognosis of patients with malignant tumors, and increasing evidence has shown a connection between sB7-H3 and NF-kappaB in tumor progression. In the present study, we demonstrate for the first time that sB7-H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NF-kappaB pathway. In this study, we observed that sB7-H3 was highly expressed in mB7-H3 positive pancreatic carcinoma (PCa) cells. Exogenous sB7-H3 significantly increased NF-kappaB activity and promoted the migration and invasion of PCa cells. Further studies proved that sB7-H3 first up-regulated TLR4 expression, then activated NF-kappaB signaling and finally promoted IL-8 and VEGF expression. In contrast, the silencing of TLR4 using a stable short hairpin RNA significantly decreased the sB7-H3-induced activity of NF-kappaB and the expression of IL-8 and VEGF in PCa cells. In vivo animal experiments further demonstrated that TLR4 knock-down tumor cells displayed a decreased ability to metastasize compared with the control tumor cells after being induced by sB7-H3. Collectively, these results demonstrate that sB7-H3 promotes invasion and metastasis through the TLR4/NF-kappaB pathway in pancreatic carcinoma cells. PMID- 27273627 TI - Cellular gatekeepers. PMID- 27273626 TI - Functional Analysis of Amorpha-4,11-Diene Synthase (ADS) Homologs from Non Artemisinin-Producing Artemisia Species: The Discovery of Novel Koidzumiol and (+)-alpha-Bisabolol Synthases. AB - The production of artemisinin, the most effective antimalarial compound, is limited to Artemisia annua. Enzymes involved in artemisinin biosynthesis include amorpha-4,11-diene synthase (ADS), amorpha-4,11-diene 12-monooxygenase (CYP71AV1) and artemisinic aldehyde Delta(11)13 reductase (DBR2). Although artemisinin and its specific intermediates are not detected in other Artemisia species, we reported previously that CYP71AV1 and DBR2 homologs were expressed in some non artemisinin-producing Artemisia plants. These homologous enzymes showed similar functions to their counterparts in A. annua and can convert fed intermediates into the following products along the artemisinin biosynthesis in planta These findings suggested a partial artemisinin-producing ability in those species. In this study, we examined genes highly homologous to ADS, the first committed gene in the pathway, in 13 Artemisia species. We detected ADS homologs in A. absinthium, A. kurramensis and A. maritima. We analyzed the enzymatic functions of all of the ADS homologs after obtaining their cDNA. We found that the ADS homolog from A. absinthium exhibited novel activity in the cyclization of farnesyl pyrophosphate (FPP) to koidzumiol, a rare natural sesquiterpenoid. Those from A. kurramensis and A. maritima showed similar, but novel, activities in the cyclization of FPP to (+)-alpha-bisabolol. The unique functions of the novel sesquiterpene synthases highly homologous to ADS found in this study could provide insight into the molecular basis of the exceptional artemisinin-producing ability in A. annua. PMID- 27273628 TI - Atomic-level analysis of membrane-protein structure. AB - Membrane proteins are substantially more challenging than natively soluble proteins as subjects for structural analysis. Thus, membrane proteins are greatly underrepresented in structural databases. Recently, focused consortium efforts and advances in methodology for protein production, crystallographic analysis and cryo-EM analysis have accelerated the pace of atomic-level structure determination of membrane proteins. PMID- 27273630 TI - Toward high-resolution computational design of the structure and function of helical membrane proteins. AB - The computational design of alpha-helical membrane proteins is still in its infancy but has already made great progress. De novo design allows stable, specific and active minimal oligomeric systems to be obtained. Computational reengineering can improve the stability and function of naturally occurring membrane proteins. Currently, the major hurdle for the field is the experimental characterization of the designs. The emergence of new structural methods for membrane proteins will accelerate progress. PMID- 27273629 TI - NMR as a tool to investigate the structure, dynamics and function of membrane proteins. AB - Membrane-protein NMR occupies a unique niche for determining structures, assessing dynamics, examining folding, and studying the binding of lipids, ligands and drugs to membrane proteins. However, NMR analyses of membrane proteins also face special challenges that are not encountered with soluble proteins, including sample preparation, size limitation, spectral crowding and sparse data accumulation. This Perspective provides a snapshot of current achievements, future opportunities and possible limitations in this rapidly developing field. PMID- 27273631 TI - Nanodiscs for structural and functional studies of membrane proteins. AB - Membrane proteins have long presented a challenge to biochemical and functional studies. In the absence of a bilayer environment, individual proteins and critical macromolecular complexes may be insoluble and may display altered or absent activities. Nanodisc technology provides important advantages for the isolation, purification, structural resolution and functional characterization of membrane proteins. In addition, the ability to precisely control the nanodisc composition provides a nanoscale membrane surface for investigating molecular recognition events. PMID- 27273634 TI - Knud Hermann Nierhaus 1941-2016. PMID- 27273632 TI - Mechanistic diversity in ATP-binding cassette (ABC) transporters. AB - ABC transporters catalyze transport reactions, such as the high-affinity uptake of micronutrients into bacteria and the export of cytotoxic compounds from mammalian cells. Crystal structures of ABC domains and full transporters have provided a framework for formulating reaction mechanisms of ATP-driven substrate transport, but recent studies have suggested remarkable mechanistic diversity within this protein family. This review evaluates the differing mechanistic proposals and outlines future directions for the exploration of ABC-transporter catalyzed reactions. PMID- 27273635 TI - Escape from epigenetic silencing of lactase expression is triggered by a single nucleotide change. PMID- 27273633 TI - Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels. AB - Ion channels gated by neurotransmitters are present across metazoans, in which they are essential for brain function, sensation and locomotion; closely related homologs are also found in bacteria. Structures of eukaryotic pentameric cysteine loop (Cys-loop) receptors and tetrameric ionotropic glutamate receptors in multiple functional states have recently become available. Here, I describe how these studies relate to established ideas regarding receptor activation and how they have enabled decades' worth of functional work to be pieced together, thus allowing previously puzzling aspects of receptor activity to be understood. PMID- 27273636 TI - Reverse transcriptases lend a hand in splicing catalysis. PMID- 27273637 TI - Noncoding RNA joins Ku and DNA-PKcs for DNA-break resistance in breast cancer. PMID- 27273638 TI - Heavy lessons in protein allostery. PMID- 27273639 TI - Systematic review of traditional Chinese medicine for geriatrics. AB - The Japan Geriatrics Society revised its criteria for the medical treatment and safety of the elderly in 2015. The Japan Geriatrics Society guidelines contain a chapter for traditional Chinese medicine (TCM; traditional medicines in East Asian countries, such as China, Japan, Korea, Taiwan, Vietnam and Singapore), because it is widely used for elderly patients and is sometimes covered by national medical insurance in Japan. The updated guidelines should be improved based on a comprehensive, systematic review and evidence grading. TCM is rapidly expanding in the literature, and is under intensive investigation in clinical trials. The objective of the present trial was to review TCM systematically and reflect the results to update the TCM chapter of the Japan Geriatrics Society guidelines. Here, we introduce the results of the systemic review of TCM for geriatrics. Geriatr Gerontol Int 2017; 17: 679-688. PMID- 27273641 TI - Costs Associated with Surgically Treated Cases of Abdominal Cystic Echinococcosis: A Single Center's Experience from 2008 to 2014, Pavia, Italy. AB - Cystic echinococcosis (CE) is a globally distributed zoonosis caused by the Echinococcus granulosus sensu lato species complex. Four approaches are available for treatment of abdominal CE: surgery, percutaneous aspiration, chemotherapy with albendazole, and watch-and-wait. Allocation of patients to these different treatment options mainly depends on the stage of the cystic lesion. However, as available guidelines are not widely followed, surgery is often applied even without the correct indication outside referral centers. This is not only a disadvantage for the patient, but also a waste of money. In this study, we evaluated the cost of the surgical approach for abdominal CE by analyzing hospitalization costs for 14 patients admitted to the General Surgery Ward at the "San Matteo" Hospital Foundation in Pavia, Italy, from 2008 through 2014. We found that the total cost of a single hospitalization, including hospital stay, surgical intervention, personnel, drugs, and administrative costs ranged from ?5,874 to 23,077 (median ?11,033) per patient. Our findings confirm that surgery can be an expensive option. Therefore, surgical intervention should be limited to cyst types that do not benefit from nonsurgical therapies and appropriate case management can best be accomplished by using a cyst stage-specific approach. PMID- 27273640 TI - Availability and Quality of Emergency Obstetric and Newborn Care in Bangladesh. AB - Bangladesh's maternal mortality and neonatal mortality remain unacceptably high. We assessed the availability and quality of emergency obstetric care (EmOC) and emergency newborn care (EmNC) services at health facilities in Bangladesh. We randomly sampled 50 rural villages and 50 urban neighborhoods throughout Bangladesh and interviewed the director of eight and nine health facilities nearest to each sampled area. We categorized health facilities into different quality levels (high, moderate, low, and substandard) based on staffing, availability of a phone or ambulance, and signal functions (six categories for EmOC and four categories for EmNC). We interviewed the directors of 875 health facilities. Approximately 28% of health facilities did not have a skilled birth attendant on call 24 hours per day. The least commonly performed EmOC signal function was administration of anticonvulsants (67%). The quality of EmOC services was high in 33% and moderate in 52% of the health facilities. The least common EmNC signal function was kangaroo mother care (7%). The quality of EmNC was high in 2% and moderate in 33% of the health facilities. Approximately one third of health facilities lack 24-hour availability of skilled birth attendants, increasing the risk of peripartum complications. Most health facilities offered moderate to high quality services for EmOC and low to substandard quality for EmNC. PMID- 27273642 TI - Opossums and Cat Fleas: New Insights in the Ecology of Murine Typhus in Galveston, Texas. AB - Murine typhus is an acute undifferentiated febrile illness caused by Rickettsia typhi The classic reservoir (Rattus spp.) and flea vector (Xenopsylla cheopis) were once culprits of murine typhus in the United States. Vector and rodent control efforts have drastically decreased the prevalence of disease, except in a few endemic foci where opossums and cat fleas play a role in transmission. Since 2012, there has been a reemergence of murine typhus in Galveston, TX. We hypothesize that opossums and cat fleas are involved in the transmission of R. typhi in Galveston. To explore this, we sought to find the seroprevalence of typhus group antibodies from opossums. We also sought to find the prevalence of R. typhi in fleas parasitizing these animals. We collected blood from 12 opossums and found that eight (66.7%) had the presence of anti-R. typhi antibodies. All opossums were infested with fleas; a total of 250 Ctenocephalides felis fleas were collected from these animals. Seven opossums (53.8%) were infested with fleas that had molecular evidence of R. typhi infection, while six (46.2%) were infested with fleas that contained Candidatus Rickettsia senegalensis, an organism closely related to R. felis The minimum flea infection rate for R. typhi was 7.0%. The minimum infection rate for Candidatus R. senegalensis was 6.1%. Our study demonstrates that fleas infected with R. typhi parasitize opossums in Galveston. It is therefore likely that opossums and their fleas play a role in the city's recent reemergence of murine typhus. PMID- 27273643 TI - Loop-Mediated Isothermal Amplification for Detection of the 5.8S Ribosomal Ribonucleic Acid Internal Transcribed Spacer 2 Gene Found in Trypanosoma brucei gambiense. AB - The loop-mediated isothermal amplification (LAMP) assay with its advantages of cost effectiveness, rapidity, and simplicity, has evolved as a sensitive and specific method for the detection of African trypanosomes. Highly sensitive LAMP reactions specific for Trypanosoma brucei rhodesiense or that recognize but do not discriminate between Trypanosoma brucei brucei, T. b. rhodesiense, Trypanosoma brucei gambiense, and Trypanosoma evansi have been developed. A sensitive LAMP assay targeting the T. b. gambiense 5.8S ribosomal RNA internal transcribed spacer 2 (5.8S-ITS2) gene is also available but this assay does not target binding sites that span the CCCA (C3A) (557-560 bps) insertion site that further differentiates T. b. gambiense from T. b. brucei Here we describe 5.8S ITS2-targeted LAMP assay that fit these criteria. The LAMP primer sets containing the T. b. gambiense-specific C3A tetranucleotide at the start of the outer forward primer sequences showed high specificity and sensitivity down to at least 0.1 fg T. b. gambiense genomic DNA. PMID- 27273644 TI - Prevalence of Hepatitis B Virus Infection in Kenya, 2007. AB - Current estimates put the prevalence of hepatitis B virus (HBV) infection in Kenya at 5-8%. We determined the HBV infection prevalence in the human immunodeficiency virus (HIV)-negative Kenyan adult and adolescent population based on samples collected from a national survey. We analyzed data from HIV negative participants in the 2007 Kenya AIDS Indicator Survey to estimate the HBV infection prevalence. We defined past or present HBV infection as presence of total hepatitis B core antibody (HBcAb), and chronic HBV infection (CHBI) as presence of both total HBcAb and hepatitis B surface antigen (HBsAg). We calculated crude and adjusted odds of HBV infection by demographic characteristics and risk factors using logistic regression analyses. Of 1,091 participants aged 15-64 years, approximately 31.5% (95% confidence interval [CI] = 28.0-35.3%) had exposure to HBV, corresponding to approximately 6.1 million (CI = 5.4-6.8 million) with past or present HBV infection. The estimated prevalence of CHBI was 2.1% (95% CI = 1.4-3.1%), corresponding to approximately 398,000 (CI = 261,000-602,000) with CHBI. CHBI is a major public health problem in Kenya, affecting approximately 400,000 persons. Knowing the HBV infection prevalence at baseline is important for planning and public health policy decision making and for monitoring the impact of viral hepatitis prevention programs. PMID- 27273645 TI - Associations Between Helminth Infections, Plasmodium falciparum Parasite Carriage and Antibody Responses to Sexual and Asexual Stage Malarial Antigens. AB - Infections with helminths and Plasmodium spp. overlap in their geographical distribution. It has been postulated that helminth infections may influence malarial transmission by altering Plasmodium falciparum gametocytogenesis. This cross-sectional study assessed the effect of helminth infections on P. falciparum gametocyte carriage and on humoral immune responses to sexual stage antigens in Gabon. Schistosoma haematobium and filarial infections as well as P. falciparum asexual forms and gametocyte carriage were determined. The antibody responses measured were to sexual (Pfs230, Pfs48/45) and asexual P. falciparum antigens (AMA1, MSP1, and GLURP). A total of 287 subjects were included. The prevalence of microscopically detectable P. falciparum asexual parasites was higher in S. haematobium-infected subjects in comparison to their uninfected counterparts (47% versus 26%, P = 0.003), but this was not different when filarial infections were considered. Plasmodium falciparum gametocyte carriage was similar between Schistosoma- or filaria-infected and uninfected subjects. We observed a significant decrease of Pfs48/45 immunoglobulin G titer in S. haematobium infected subjects (P = 0.037), whereas no difference was seen for Pfs230 antibody titer, nor for antibodies to AMA1, MSP1, or GLURP. Our findings suggest an effect of S. haematobium on antibody responses to some P. falciparum gametocyte antigens that may have consequences for transmission-blocking immunity. PMID- 27273646 TI - The Impact of an Intervention to Improve Malaria Care in Public Health Centers on Health Indicators of Children in Tororo, Uganda (PRIME): A Cluster-Randomized Trial. AB - Optimizing quality of care for malaria and other febrile illnesses is a complex challenge of major public health importance. To evaluate the impact of an intervention aiming to improve malaria case management on the health of community children, a cluster-randomized trial was conducted from 2010-2013 in Tororo, Uganda, where malaria transmission is high. Twenty public health centers were included; 10 were randomized in a 1:1 ratio to intervention or control. Households within 2 km of health centers provided the sampling frame for the evaluation. The PRIME intervention included training in fever case management using malaria rapid diagnostic tests (mRDTs), patient-centered services, and health center management; plus provision of mRDTs and artemether-lumefantrine. Cross-sectional community surveys were conducted at baseline and endline (N = 8,766), and a cohort of children was followed for approximately 18 months (N = 992). The primary outcome was prevalence of anemia (hemoglobin < 11.0 g/dL) in children under 5 years of age in the final community survey. The intervention was delivered successfully; however, no differences in prevalence of anemia or parasitemia were observed between the study arms in the final community survey or the cohort. In the final survey, prevalence of anemia in children under 5 years of age was 62.5% in the intervention versus 63.1% in control (adjusted risk ratio = 1.01; 95% confidence interval = 0.91-1.13; P = 0.82). The PRIME intervention, focusing on training and commodities, did not produce the expected health benefits in community children in Tororo. This challenges common assumptions that improving quality of care and access to malaria diagnostics will yield health gains. PMID- 27273647 TI - Evidence of Rickettsia and Orientia Infections Among Abattoir Workers in Djibouti. AB - Of 49 workers at a Djiboutian abattoir, eight (16%, 95% confidence interval [CI]: 9-29) were seropositive against spotted fever group rickettsiae (SFGR), two (4%, 95% CI: 1-14) against typhus group rickettsiae, and three (6%, 95% CI: 2-17) against orientiae. One worker (9%, 95% CI: 2-38) seroconverted against orientiae during the study period. This is the first evidence of orientiae exposure in the Horn of Africa. SFGR were also identified by polymerase chain reaction in 32 of 189 (11%, 95% CI: 8-15) tick pools from 26 of 72 (36%) cattle. Twenty-five (8%, 95% CI: 6-12) tick pools were positive for Rickettsia africae, the causative agent of African tick-bite fever. Health-care providers in Djibouti should be aware of the possibility of rickettsiae infections among patients, although further research is needed to determine the impact of these infections in the country. PMID- 27273648 TI - Two Unusual Cases of Human Immunodeficiency Virus-Negative Patients with Talaromyces marneffei Infection. AB - Talaromyces marneffei (formerly known as Penicillium marneffei) is a dimorphic fungus endemic in south and southeast Asia. It is not only commonly found in human immunodeficiency virus (HIV)-infected patients, but also among HIV-negative immunocompromised patients. The infection caused by this pathogen can disseminate hematogenously to other locations. Herein, we report for the first time two cases complicated with a rare disease or involving a rare site: in the first case, T. marneffei infection was complicated by Langerhans cell histiocytosis, whereas the second case showed clear etiological evidence of pleural nodules and pleural effusion caused by T. marneffei and diagnosed by thoracoscopic pleural biopsy. PMID- 27273649 TI - Characteristics and Risk Factors for Fatality in Patients with Dengue Hemorrhagic Fever, Taiwan, 2014. AB - An unprecedented dengue outbreak involving more than 15,000 infections, including 136 dengue hemorrhagic fever (DHF) cases and 20 fatalities, occurred in Taiwan in 2014. The median age of the DHF cases was 71 years (range: 4-92 years) and most of them (N = 100, 73.5%) had comorbidities, of which the majority were hypertension (56%) and diabetes mellitus (DM; 27%). Only approximately half of the DHF cases (59/136) were classified as severe dengue, based on the 2009 WHO revised dengue classification. The fatality rate for this DHF outbreak was 14.7%. DM (odds ratio [OR] = 3.60, 95% confidence interval [CI] = 1.22-10.63) and presentation with severe plasma leakage (OR = 6.42, 95% CI = 1.76-23.63) were independent risk factors for fatality. PMID- 27273650 TI - Pig-to-nonhuman primate solid organ xenografting: recent achievements on the road to first-in-man explorations. PMID- 27273651 TI - A clinical view on the development of technology-based tools in managing Parkinson's disease. AB - Recently, quantitative, objective, and easy-to-use technology-based tools that can assess PD features over long time periods have been developed and generate clinically relevant and comparable patient information. Herein, we present a clinician's view on technological developments that have the potential to revolutionize clinical management concepts in PD. According to prominent examples in clinical medicine (e.g., blood glycosylated hemoglobin and blood pressure), we argue that the consideration of technology-based assessment in the clinical management of PD must be based on specific assumptions: (1) It provides a valid and accurate parameter of a clinically relevant feature of the disease; (2) there is confirmed evidence that the parameter has an ecologically relevant effect on the specific clinical application; (3) a target range can be defined wherein the parameter reflects the adequate treatment response; and (4) implementation is simple to allow repetitive use. Currently, there are no technology-based tools available that fulfil all these assumptions; however, assessments of akinesia, dyskinesia, motor fluctuations, physical inactivity, gait impairment, and postural instability seem relatively close to the specifications described. An iterative process of integration is recommended to bring technology-based tools into clinical practice. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27273652 TI - The long-term differential achievement effects of school socioeconomic composition in primary education: A propensity score matching approach. AB - BACKGROUND: The effects of school socio-economic composition on student achievement growth trajectories have been a hot topic of discussion among politicians around the world for many years. However, the bulk of research investigating school socio-economic composition effects has been limited in important ways. AIMS: In an attempt to overcome the flaws in earlier research on school socio-economic composition effects, this study used data from a large sample, followed students throughout primary education, addressed selection bias problems, identified the grade(s) in which school socio-economic composition mattered the most, and studied the differential effects of school socio-economic composition by individual socio-economic status (SES). SAMPLE: In a longitudinal design with seven occasions of data collection, the authors drew on a sample of N = 3,619 students (age at T1 about 5 years, age at T7 about 12 years) from 151 primary schools in Flanders (the northern part of Belgium). METHOD: Students in low-, medium-, high-, and mixed-SES schools were matched using propensity scores. To compare students' achievement growth trajectories in the different school compositions, multilevel regression modelling with repeated measurements was applied. RESULTS: The results showed that students had more positive achievement growth in high-SES as compared to low-SES and mixed-SES schools. In two of the three comparisons, students in mixed-SES schools showed the lowest math development. The negative effects of mixed-SES schools on math achievement growth were the strongest for high-SES students. CONCLUSIONS: Our findings contribute to the ongoing discussion on the effects of school socio-economic composition on student achievement growth. PMID- 27273654 TI - The Role of Sleep Disturbance in Suicidal and Nonsuicidal Self-Injurious Behavior among Adolescents. AB - The relationship between different sleep disturbances and self-harm thoughts and behaviors was examined among 223 adolescents presenting to a community clinic for mood disorders and suicidal and nonsuicidal self-injurious behaviors. Two-thirds of the adolescents reported nightly, severe sleep complaints. Relative to adolescents without significant sleep complaints, patients with severe sleep complaints at the time of clinic entry endorsed significantly more engagement in nonsuicidal self-injury. Middle insomnia and circadian reversal were both significant predictors of suicide attempts. Terminal insomnia was significantly associated with suicidal ideation. Results support the importance of assessing sleep difficulties among adolescents at risk for suicide. PMID- 27273653 TI - Photodynamic therapy inhibit Fibroblast Growth Factor-10 induced keratinocyte differentiation and proliferation through ROS in Fibroblast Growth Factor Receptor-2b pathway. AB - 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is known to be effective in several skin diseases such as acne, actinic keratoses, condyloma acuminata. However, some detailed mechanisms of ALA-PDT to treat these skin diseases still remain elusive. In this study, we aimed to investigate mechanism of ALA-PDT in in vitro and in-vivo models. For in vitro, we use human keratinocyte cell line (HaCaT) cells. CCK-8 was used to detect cell proliferation activity, immunofluorescence and western blotting method to detect the content of keratin (K)1, K6, K16, protein kinase C (PKC), fibroblast growth factor receptor-2b (FGFR2b) protein, ELISA and RT-PCR to detect expression of interleukin (IL) 1alpha in the cell supernatant, and detect reactive oxygen species (ROS). For in vivo, we use 20 rabbits to induce hyperkeratosis acne model in their ear. Dermatoscope was used to see follicle hyperkeratosis and skin biopsy to analyze histology and immunohistochemical of PKC, FGFR2b, K1, K6 and K16. Results from this study suggest that ROS stimulated by ALA-PDT lead to inhibition of FGFR2b pathway in PKC downstream to cause reduction of IL1alpha expression, and eventually, keratinocytes differentiation and proliferation. Our data thus reveal a treatment mechanism of ALA-PDT underlying hyperkeratosis related dermatoses. PMID- 27273655 TI - Strong Electron-Deficient Polymers Lead to High Electron Mobility in Air and Their Morphology-Dependent Transport Behaviors. AB - Planar backbone, locked conformation, and low lowest unoccupied molecular orbital level provide polymer F4 BDOPV-2T with ultrahigh electron mobilities of up to 14.9 cm(2) V(-1) s(-1) and good air stability. It is found that the nonlinear transfer curves can be tuned to near-ideal ones by changing fabrication conditions, indicating that film morphology largely contributes to the nonlinear transfer curves in high-mobility conjugated polymers. PMID- 27273656 TI - Hexaazatrinaphthylene Derivatives: Efficient Electron-Transporting Materials with Tunable Energy Levels for Inverted Perovskite Solar Cells. AB - Hexaazatrinaphthylene (HATNA) derivatives have been successfully shown to function as efficient electron-transporting materials (ETMs) for perovskite solar cells (PVSCs). The cells demonstrate a superior power conversion efficiency (PCE) of 17.6 % with negligible hysteresis. This study provides one of the first nonfullerene small-molecule-based ETMs for high-performance p-i-n PVSCs. PMID- 27273657 TI - Risk factor analysis of hepatitis C virus seropositivity in Iranian blood donors: a case-control study. AB - BACKGROUND: Due to blood screening and blood donor selection, the prevalence of hepatitis C virus (HCV) is expected to be lower among blood donors compared to the general population. The effective control of blood-transmitted infectious diseases should be one of the goals of public health. Thus, this case-control study was conducted to evaluate the risk factors of HCV in a representative sample of blood donors in Iran. STUDY DESIGN AND METHODS: A case-control study was conducted on HCV-negative and on serologically confirmed HCV-positive donors across the country from 2009 to 2013. Univariate logistic regression, multiple logistic regression, and subgroup analyses were performed to assess the risk factors in first-time blood donors (FTs) and repeat blood donors (RDs) independently. RESULTS: A total of 970 cases and 1542 controls were selected from the cohort of Iranian blood donors registered in the Iran Blood Transfusion Organization. Intravenous (IV) drug abuse (ORFT , 6.42; 95% CI, 3.34-12.34; and ORRD , 27.62; 95% CI, 12.58-60.62), living with an IV drug abuser (ORFT , 3.47; 95% CI, 1.26-9.55; and ORRD , 6.95; 95% CI, 1.54-31.34), prison history (ORFT , 2.4; 95% CI, 1.48-3.88; and ORRD , 2.42; 95% CI, 1.38-4.27), sharing personal razors (ORFT , 2.00; 95% CI, 1.01-3.96; and ORRD , 5.62; 95% CI, 2.65-11.89), and medical exposure (ORFT , 1.97; 95% CI, 1.15-3.37; and ORRD , 2.19; 95% CI, 1.27 3.76) were significant independent risk factors in both types of blood donation. CONCLUSION: The findings of this analytic study on HCV exposure in Iranian blood donors conforms to those of international studies. Behavioral and medical factors should be examined in the donor health screening process. PMID- 27273669 TI - R.JIVE for exploration of multi-source molecular data. AB - : The integrative analysis of multiple high-throughput data sources that are available for a common sample set is an increasingly common goal in biomedical research. Joint and individual variation explained (JIVE) is a tool for exploratory dimension reduction that decomposes a multi-source dataset into three terms: a low-rank approximation capturing joint variation across sources, low rank approximations for structured variation individual to each source and residual noise. JIVE has been used to explore multi-source data for a variety of application areas but its accessibility was previously limited. We introduce R.JIVE, an intuitive R package to perform JIVE and visualize the results. We discuss several improvements and extensions of the JIVE methodology that are included. We illustrate the package with an application to multi-source breast tumor data from The Cancer Genome Atlas. AVAILABILITY AND IMPLEMENTATION: R.JIVE is available via the Comprehensive R Archive Network (CRAN) under the GPLv3 license: https://cran.r-project.org/web/packages/r.jive/ CONTACT: elock@umn.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27273670 TI - MetalPredator: a web server to predict iron-sulfur cluster binding proteomes. AB - MOTIVATION: The prediction of the iron-sulfur proteome is highly desirable for biomedical and biological research but a freely available tool to predict iron sulfur proteins has not been developed yet. RESULTS: We developed a web server to predict iron-sulfur proteins from protein sequence(s). This tool, called MetalPredator, is able to process complete proteomes rapidly with high recall and precision. AVAILABILITY AND IMPLEMENTATION: The web server is freely available at: http://metalweb.cerm.unifi.it/tools/metalpredator/ CONTACT: andreini@cerm.unifi.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27273671 TI - MIA: non-targeted mass isotopolome analysis. AB - MIA detects and visualizes isotopic enrichment in gas chromatography electron ionization mass spectrometry (GC-EI-MS) datasets in a non-targeted manner. It provides an easy-to-use graphical user interface that allows for visual mass isotopomer distribution analysis across multiple datasets. MIA helps to reveal changes in metabolic fluxes, visualizes metabolic proximity of isotopically enriched compounds and shows the fate of the applied stable isotope labeled tracer. AVAILABILITY AND IMPLEMENTATION: Linux and Windows binaries, documentation, and sample data are freely available for download at http://massisotopolomeanalyzer.lu MIA is a stand-alone application implemented in C ++ and based on Qt5, NTFD and the MetaboliteDetector framework. CONTACT: karsten.hiller@uni.lu. PMID- 27273672 TI - Predicting regulatory variants with composite statistic. AB - MOTIVATION: Prediction and prioritization of human non-coding regulatory variants is critical for understanding the regulatory mechanisms of disease pathogenesis and promoting personalized medicine. Existing tools utilize functional genomics data and evolutionary information to evaluate the pathogenicity or regulatory functions of non-coding variants. However, different algorithms lead to inconsistent and even conflicting predictions. Combining multiple methods may increase accuracy in regulatory variant prediction. RESULTS: Here, we compiled an integrative resource for predictions from eight different tools on functional annotation of non-coding variants. We further developed a composite strategy to integrate multiple predictions and computed the composite likelihood of a given variant being regulatory variant. Benchmarked by multiple independent causal variants datasets, we demonstrated that our composite model significantly improves the prediction performance. AVAILABILITY AND IMPLEMENTATION: We implemented our model and scoring procedure as a tool, named PRVCS, which is freely available to academic and non-profit usage at http://jjwanglab.org/PRVCS CONTACT: wang.junwen@mayo.edu, jliu@stat.harvard.edu, or limx54@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 27273674 TI - The long story of the Maillard reaction: the beginning of the second century. PMID- 27273673 TI - Accurate self-correction of errors in long reads using de Bruijn graphs. AB - Motivation: New long read sequencing technologies, like PacBio SMRT and Oxford NanoPore, can produce sequencing reads up to 50 000 bp long but with an error rate of at least 15%. Reducing the error rate is necessary for subsequent utilization of the reads in, e.g. de novo genome assembly. The error correction problem has been tackled either by aligning the long reads against each other or by a hybrid approach that uses the more accurate short reads produced by second generation sequencing technologies to correct the long reads. Results: We present an error correction method that uses long reads only. The method consists of two phases: first, we use an iterative alignment-free correction method based on de Bruijn graphs with increasing length of k -mers, and second, the corrected reads are further polished using long-distance dependencies that are found using multiple alignments. According to our experiments, the proposed method is the most accurate one relying on long reads only for read sets with high coverage. Furthermore, when the coverage of the read set is at least 75*, the throughput of the new method is at least 20% higher. Availability and Implementation: LoRMA is freely available at http://www.cs.helsinki.fi/u/lmsalmel/LoRMA/ . Contact: leena.salmela@cs.helsinki.fi. PMID- 27273675 TI - Defining heterogeneity within bacterial populations via single cell approaches. AB - Bacterial populations are heterogeneous, which in many cases can provide a selective advantage during changes in environmental conditions. In some instances, heterogeneity exists at the genetic level, in which significant allelic variation occurs within a population seeded by a single cell. In other cases, heterogeneity exists due to phenotypic differences within a clonal, genetically identical population. A variety of mechanisms can drive this latter strategy. Stochastic fluctuations can drive differential gene expression, but heterogeneity in gene expression can also be driven by environmental changes sensed by individual cells residing in distinct locales. Utilizing multiple single cell approaches, workers have started to uncover the extent of heterogeneity within bacterial populations. This review will first describe several examples of phenotypic and genetic heterogeneity, and then discuss many single cell approaches that have recently been applied to define heterogeneity within bacterial populations. PMID- 27273676 TI - Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients. AB - BACKGROUND: Oral nimodipine is standard therapy for patients suffering an aneurysmal subarachnoid hemorrhage (aSAH). During a national drug shortage, nimodipine therapy was shortened from a 21-day course to a 14-day course at our institution. OBJECTIVE: The objective of this study was to compare neurological outcomes among patients who had previously received the standard duration of therapy compared with those who received a shortened duration as a result of the national drug shortage. METHODS: This retrospective cohort study evaluated adult patients receiving nimodipine for aSAH from January 2012 to August 2013. Neurological outcome, graded by Modified Rankin Scale (mRS) at hospital discharge, was compared between patients receiving a shortened course and those receiving the standard duration of nimodipine. RESULTS: A total of 199 aSAH patients were included in the analysis. There were 164 patients in the standard duration and 35 patients in the shortened-duration group. Baseline patient severity of illness, assessed by SAPS II (Simplified Acute Physiology Score), and severity of aSAH, assessed by Fisher grade, and Hunt and Hess grade scores, did not differ between the treatment groups. A shortened duration of nimodipine was not associated with a higher risk of a poor neurological outcome defined by mRS (odds ratio = 1.85; 95% CI = 0.54-6.32; P = 0.32). Mortality rates were similar between the groups. CONCLUSIONS: A 14-day course of nimodipine therapy was not associated with worse neurological outcomes in aSAH patients at one institution. More studies are needed prior to recommending a shortened duration of nimodipine therapy in all aSAH patients. PMID- 27273677 TI - Beneficial Effects of a Cholecalciferol Supplementation Regimen for Elderly Patients With a Suboptimal Level of 25-Hydroxyvitamin D. PMID- 27273678 TI - Pharmacist-Provided Medication Management in Interdisciplinary Transitions in a Community Hospital (PMIT). AB - BACKGROUND: Medication management during transitions of care (TOC) impacts clinical outcomes. Published literature on TOC implementation is increasing, but data remains limited regarding the optimal role for the inpatient pharmacist, particularly in the community health setting. OBJECTIVE: To evaluate the impact of a dedicated inpatient TOC pharmacist on re-presentations following discharge. METHODS: This is a prospective study with historical control. All adult patients discharging home from study units were eligible. The TOC pharmacist (1) reviewed medication history and admission reconciliation, (2) met the patient/caregiver to assess barriers, (3) reviewed discharge reconciliation, (4) performed discharge education, and (5) communicated with next level of care. The primary outcome was 30 day re-presentation rate. Secondary outcomes included 60, 90, and 365 day re presentation rates. IRB approval was obtained. RESULTS: Three hundred and eighty four patients met inclusion criteria. When compared to 1,221 control patients, the intervention had an 11% absolute and 50.2% relative reduction in 30 day re presentation rate (OR 0.43, 95% CI 0.30-0.61, NNT 9). Reductions in re presentations at 60, 90 and 365 days remained statistically significant. Utilization avoidance was $786,347. For every $1 invested in pharmacist time, $12 was saved. The TOC pharmacist made a total of 904 interventions (mean 2.4 per patient). CONCLUSION: This study provides new information from previous studies and represents the largest study with significant and sustained reductions in re presentations. Integrating a pharmacist into an interdisciplinary team for medication management during TOC in a community health system is beneficial for patients and financially favorable for the institution. PMID- 27273679 TI - Recovery of baseline lung function after pulmonary exacerbation in children with primary ciliary dyskinesia. AB - RATIONALE: Spirometry in children with cystic fibrosis (CF) frequently fails to return to baseline after treatment for a pulmonary exacerbation. It is unclear whether the same is true for children with primary ciliary dyskinesia (PCD). OBJECTIVES: To determine in children with PCD treated with intravenous antibiotics for a pulmonary exacerbation: (1) the proportion who recover to baseline forced expiratory volume at 1 sec (FEV1 ) within 3 months after treatment and (2) to try to identify factors which are associated with failure to regain pre-exacerbation FEV1 . METHODS: Cohort study using the PCD database for children at the Royal Brompton Hospital, 2003-2013. We selected the first pulmonary exacerbation treated with intravenous antibiotics. The best FEV1 within 3 months after treatment was compared to the best FEV1 in the 12 months before treatment (baseline). Recovery to baseline was defined as any FEV1 after treatment that was greater than or equal to 90% of the baseline FEV1 . RESULTS: 32/150 children (21%) had at least one pulmonary exacerbation. 23/30 (77%) regained baseline spirometry within 3 months of treatment. There was no difference between responders and non-responders in any baseline characteristics. CONCLUSIONS: Around 25% of children with PCD fail to recover to baseline lung function within 3 months following treatment for a pulmonary exacerbation, similar to CF. Better treatment strategies are needed, and the results also suggest that prevention of exacerbations would be a useful end-point in clinical trials. Pediatr Pulmonol. 2016;51:1362-1366. (c) 2016 Wiley Periodicals, Inc. PMID- 27273681 TI - Quality of life in adolescents and adults with CHARGE syndrome. AB - Health-related Quality of Life and the Impact of Childhood Neurologic Disability Scale were collected for 53 patients with CHARGE syndrome aged 13-39 years with a mean academic level of 4th grade. The most prevalent new and ongoing issues included bone health issues, sleep apnea, retinal detachment, anxiety, and aggression. Sleep issues were significantly correlated with anxiety, self-abuse, conduct problems, and autistic-like behaviors. Problems with overall health, behavior, and balance most affected the number of social activities in the individual's life. Sensory impairment most affected relationships with friends. Two contrasting case studies are presented and demonstrate that the quality of life exists on a broad spectrum in CHARGE syndrome, just as its physical features range from mild to very severe. A multitude of factors, including those beyond the physical manifestations, such as anxiety and sleep problems, influence quality of life and are important areas for intervention. (c) 2016 Wiley Periodicals, Inc. PMID- 27273682 TI - Indirect cavernous carotid fistula in a 12-year-old girl. AB - We present a very rare case of indirect cavernous carotid fistula (CCF) in a 12 year-old girl. Indirect CCF is extremely rare in the paediatric population. A 12 year-old girl presented with a 7-month history of frontal headaches and intermittent left-sided proptosis. On examination, she had dilated and engorged scleral veins on the left eye, mild dysdiadochokinesia and past pointing on the left side. A brain computer tomography with contrast, brain magnetic resonance imaging (MRI) and interventional radiography (IR) cerebral angiogram confirmed the diagnosis of CCF. The CCF was embolized and a follow-up brain MRI and an IR cerebral angiogram were conducted over the course of 8 months that revealed no evidence of residual CCF. CCF, though rare in the paediatric population, should be highly considered in the differential diagnosis when dilated scleral veins, proptosis and dysdiadokinesis are present in the clinical setting. Prompt treatment has good prognostic results. PMID- 27273680 TI - Expression of Bcl-2 19-kDa interacting protein 3 predicts prognosis after ampullary carcinoma resection. AB - BACKGROUND: An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC. METHODS: The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated. RESULTS: The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC. CONCLUSIONS: BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens. PMID- 27273683 TI - A rare case of appendicitis incarcerated in an inguinal hernia. AB - Amyand's hernia was coined after Claudius Amyand (1660-1740), who was the first to describe the presence of a perforated appendix in a hernial sac and also was the first to perform a successful appendectomy in 1735. It is an exceptionally rare condition in which the hernia itself contains the appendix, which may not necessarily be inflamed. The presence of an inflamed appendix further contributes to the rarity of this case. We report a case of acute appendicitis brought on by its incarceration in the inguinal hernia. PMID- 27273684 TI - Delayed iliacus compartment syndrome following femoral artery puncture: case report and literature review. AB - Iliacus compartment syndrome is a rare retroperitoneal compartment neuropathy caused by bleeding within the iliacus muscle leading to hematoma formation and compression upon the femoral nerve, causing both sensory and motor deficits. A 75 year-old Caucasian man presented with severe right hip pain associated with motor and sensory deficit in the right lower extremity, 2 weeks post elective balloon aortic valvuloplasty for critical aortic stenosis. A non-contrast computed tomography scan revealed low-attenuation areas in keeping with an iliacus hematoma. An iliacus fasciotomy and hematoma evacuation was performed with retroperitoneal approach. The patient reported marked reduction in his groin pain with clinical improvement of the right hip flexion though the sensory deficit was unchanged. On Day 3, postoperatively the patient died from respiratory and multi organ failure. Iliac hematomas are rare and can be caused by traumatic and non traumatic injury, and can be exacerbated by complications of anticoagulant therapy. Delaying surgical evacuation of the hematoma can lead to prolonged or permanent disability. However, there are other reports describing good recovery with non-operative management. Non-surgical intervention is recommended if radiological studies do not explicitly confirm the presence of a discreet hematoma compressing the femoral nerve, unless progression of symptoms increases. PMID- 27273685 TI - Art-of-Living Training: Developing an Intervention for Students to Increase Art of-Living. AB - BACKGROUND: Art-of-living describes a mindful and self-determined way of dealing with one's self and way of life. It is related to measures of well-being. Art-of living is based on strategies and attitudes which can be learned and therefore can be changed. Two types of training for students to increase art-of-living were developed and tested in two studies to determine the effects on art-of-living measures. METHODS: Study 1 dealt with the initial examination of whether it is possible to enhance the art-of-living by training selected art-of-living strategies. Therefore, training with three conditions was developed and conducted with secondary school students (ages 16-19). In Study 2, a second art-of-living training was developed and conducted with children from primary school (ages 8 11). RESULTS: In Study 1, the art-of-living measures increased significantly for the training conditions compared to a control group. In addition, Study 2 showed that higher levels of the art-of-living lead to a better quality of life. CONCLUSIONS: In summary, the training successfully enhanced art-of-living. Limitations on and benefits of utilising the art-of-living training are discussed. PMID- 27273686 TI - Comment: Gabapentin: Abuse, Dependence, and Withdrawal. PMID- 27273687 TI - Limited Evidence on the Management of Respiratory Tract Infections in Down's Syndrome: A Systematic Review. AB - AIMS: To systematically review the effectiveness of preventative and therapeutic interventions for respiratory tract infections (RTIs) in people with Down's syndrome. METHODS: Databases were searched for any published and ongoing studies of respiratory tract diseases in children and adults with Down's syndrome. These databases were searched for controlled trials, cohort studies and controlled before-after studies. Trial registries were searched for ongoing studies. Initially, all study types were included to provide a broad overview of the existing evidence base. However, those with a critical risk of bias were excluded using the Cochrane Risk of Bias tool. RESULTS: A total of 13,575 records were identified from which 5 studies fulfilled the eligibility criteria and 3 fulfilled our criteria for data extraction. One randomized controlled trial of moderate risk of bias compared zinc therapy with placebo. Outcome data were only reported for 50 (78%) children who presented with extreme symptoms; no benefit of zinc therapy was found. One non-randomized controlled trial with serious risk of bias included 26 children and compared pidotimod (an immunostimulant) with no treatment; pidotimod was associated with fewer upper RTI recurrences compared with no treatment (1.43 vs. 3.82). A prospective cohort study with moderate risk of bias compared 532 palivizumab treated children with 233 untreated children and found that children treated with palivizumab had fewer respiratory syncytial virus-related hospitalization (23 untreated and 8 treated), but the same number of overall RTI-related hospitalizations (73 untreated and 74 treated) in the first 2 years of life. CONCLUSIONS: The evidence base for the management of RTIs in people with Down's syndrome is incomplete; current studies included children only and carry a moderate to serious risk of bias. Methodologic rigorous studies are warranted to guide clinicians in how best to prevent and treat RTIs in children with Down's syndrome. PMID- 27273690 TI - Tuberculosis Cervical Adenitis: Management Dilemmas. AB - Peripheral lymphadenopathy (scrofula) is the second most common site for childhood tuberculosis. Paradoxical reactions are commonly seen even in immunocompetent children after therapy is initiated, and this can lead to draining sinus tracts. We describe a multimodal therapeutic option of antituberculosis therapy, corticosteroids and therapeutic ultrasound-guided nodal aspiration in an adolescent with massive cervical adenopathy. PMID- 27273688 TI - The Epidemiology of Hand, Foot and Mouth Disease in Asia: A Systematic Review and Analysis. AB - CONTEXT: Hand, foot and mouth disease (HFMD) is a widespread pediatric disease caused primarily by human enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV A16). OBJECTIVE: This study reports a systematic review of the epidemiology of HFMD in Asia. DATA SOURCES: PubMed, Web of Science and Google Scholar were searched up to December 2014. STUDY SELECTION: Two reviewers independently assessed studies for epidemiologic and serologic information about prevalence and incidence of HFMD against predetermined inclusion/exclusion criteria. DATA EXTRACTION: Two reviewers extracted answers for 8 specific research questions on HFMD epidemiology. The results are checked by 3 others. RESULTS: HFMD is found to be seasonal in temperate Asia with a summer peak and in subtropical Asia with spring and fall peaks, but not in tropical Asia; evidence of a climatic role was identified for temperate Japan. Risk factors for HFMD include hygiene, age, gender and social contacts, but most studies were underpowered to adjust rigorously for confounding variables. Both community-level and school-level transmission have been implicated, but their relative importance for HFMD is inconclusive. Epidemiologic indices are poorly understood: No supporting quantitative evidence was found for the incubation period of EV-A71; the symptomatic rate of EV-A71/Coxsackievirus A16 infection was from 10% to 71% in 4 studies; while the basic reproduction number was between 1.1 and 5.5 in 3 studies. The uncertainty in these estimates inhibits their use for further analysis. LIMITATIONS: Diversity of study designs complicates attempts to identify features of HFMD epidemiology. CONCLUSIONS: Knowledge on HFMD remains insufficient to guide interventions such as the incorporation of an EV-A71 vaccine in pediatric vaccination schedules. Research is urgently needed to fill these gaps. PMID- 27273689 TI - Cardiac Myosin Epitopes Recognized by Autoantibody in Acute and Convalescent Rheumatic Fever. AB - BACKGROUND: Acute rheumatic fever (ARF) is an autoimmune disorder associated with Streptococcus pyogenes infection. A prevailing hypothesis to account for this disease is that epitopes of self-antigens, such as cardiac myosin react to antibodies against S. pyogenes. The goal of our study was to confirm disease epitopes of cardiac myosin, identify immunodominant epitopes and to monitor the epitope response pattern in acute and convalescent rheumatic fever. METHODS: Enzyme-linked immunosorbant assays were used to determine epitopes immunodominant in acute disease and to track the immune response longitudinally to document any changes in the epitope pattern in convalescent sera. Multiplex fluorescence immunoassay was used to correlate anti-streptolysin O (ASO) and anti-human cardiac myosin antibodies. RESULTS: Disease-specific epitopes in rheumatic fever were identified as S2-1, 4 and 8. Epitopes S2-1, 4, 8 and 9 were found to be immunodominant in acute sera and S2-1, 8, 9, 29 and 30 in the convalescent sera. Frequency analysis showed that 50% of the ARF subjects responded to S2-8. S2-8 responders tended to maintain their epitope pattern throughout the convalescent period, whereas the S2-8 nonresponders tended to spread their responses to other epitopes later in the immune response. There was a significant correlation between anti-cardiac myosin and ASO titers. In addition, S2-8 responders showed elevated ASO titers compared with S2-8 non responders. CONCLUSION: Our studies confirm the existence of S2-1, 4 and 8 as disease-specific epitopes. We provide evidence that cardiac myosin S2-8 responders remain epitope stable in convalescence, whereas S2-8 nonresponders shift to neoepitopes. Multiplex data indicated a correlation between elevated ASO and anti-human cardiac myosin antibody titers. Mapping of cardiac myosin epitopes recognized in rheumatic fever sera may identify immunophenotypes of rheumatic fever. PMID- 27273691 TI - Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY. AB - This review summarizes a prospective, longitudinal 10-year study in Rochester, NY, with virtually every clinically diagnosed acute otitis media (AOM) confirmed by bacterial culture of middle ear fluid. Children experiencing 3 episodes within 6 months or 4 episodes in 12 months were considered stringently defined otitis prone (sOP). We found stringent diagnosis compared with clinical diagnosis reduced the frequency of children meeting the OP definition from 27% to 6% resulting in 14.8% and 2.4% receiving tympanostomy tubes, respectively. Significantly more often respiratory syncytial virus infection led to AOM in sOP than non-otitis-prone children that correlated with diminished total respiratory syncytial virus-specific serum IgG. sOP children produced low levels of antibody to Streptococcus pneumoniae and Haemophilus influenzae candidate vaccine protein antigens and to routine pediatric vaccines. sOP children generated significantly fewer memory B cells, functional and memory T cells to otopathogens following nasopharyngeal colonization and AOM than non-otitis-prone children and they had defects in antigen-presenting cells. PMID- 27273692 TI - Two familial cases of Olmsted-like syndrome with a G573V mutation of the TRPV3 gene. AB - Olmsted syndrome (OS) is a rare disease, characterized by symmetrical, sharply defined, hyperkeratotic, mutilating plaques on the palms and soles, which are associated with periorificial keratotic plaques. Other clinical manifestations of OS include diffuse alopecia, leucokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic linear streaks, follicular hyperkeratosis and constriction of the digits. A recent study identified de novo mutations in the gene for transient receptor potential vanilloid 3 (TRPV3), causing constitutive activation of the TRPV3 channel, as a cause of OS. We report familial inheritance of OS in a family from Mongolia, which was caused by a previously undescribed G573V point mutation in TRPV3. To date, mutations in the G573 residue of TRPV3 have been reported in seven cases of OS: G573S in five cases, and G573C and G573A mutations in one case each. We present a Mongolian familial case of G573V point mutation in TRPV3. PMID- 27273693 TI - Target geometry and rigidity determines laser-induced cavitation bubble transport and nanoparticle productivity - a high-speed videography study. AB - Laser-induced cavitation has mostly been studied in bulk liquid or at a two dimensional wall, although target shapes for the particle synthesis may strongly affect bubble dynamics and interfere with particle productivity. We investigated the dynamics of the cavitation bubble induced by pulsed-laser ablation in liquid for different target geometries with high-speed laser microsecond videography and focus on the collapse behaviour. This method enables us observations in a high time resolution (intervals of 1 MUs) and single-pulse experiments. Further, we analyzed the nanoparticle productivity, the sizes of the synthesized nanoparticles and the evolution of the bubble volume for each different target shape and geometry. For the ablation of metal (Ag, Cu, Ni) wire tips a springboard-like behaviour after the first collapse is observed which can be correlated with vertical projectile motion. Its turbulent friction in the liquid causes a very efficient transport and movement of the bubble and ablated material into the bulk liquid and prevents particle redeposition. This effect is influenced by the degree of freedom of the wire as well as the material properties and dimensions, especially the Young's modulus. The most efficient and largest bubble movement away from the wire was observed for a thin (500 MUm) silver wire with velocities up to 19.8 m s(-1) and for materials with a small Young's modulus and flexural rigidity. We suggest that these observations may contribute to upscaling strategies and increase of particle yield towards large synthesis of colloids based on targets that may continuously be fed. PMID- 27273694 TI - Quantitative DWI implemented after DCE-MRI yields increased specificity for BI RADS 3 and 4 breast lesions. AB - PURPOSE: To assess if specificity can be increased when semiautomated breast lesion analysis of quantitative diffusion-weighted imaging (DWI) is implemented after dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) in the workup of BI-RADS 3 and 4 breast lesions larger than 1 cm. MATERIALS AND METHODS: In all, 120 consecutive patients (mean-age, 48 years; age range, 23-75 years) with 139 breast lesions (>=1 cm) were examined (2010-2014) with 1.5T DCE-MRI and DWI (b = 0, 50, 200, 500, 800, 1000 s/mm2 ) and the BI-RADS classification and histopathology were obtained. For each lesion malignancy was excluded using voxelwise semiautomated breast lesion analysis based on previously defined thresholds for the apparent diffusion coefficient (ADC) and the three intravoxel incoherent motion (IVIM) parameters: molecular diffusion (Dslow ), microperfusion (Dfast ), and the fraction of Dfast (ffast ). The sensitivity (Se), specificity (Sp), and negative predictive value (NPV) based on only IVIM parameters combined in parallel (Dslow , Dfast , and ffast ), or the ADC or the BI-RADS classification by DCE-MRI were compared. Subsequently, the Se, Sp, and NPV of the combination of the BI-RADS classification by DCE-MRI followed by the IVIM parameters in parallel (or the ADC) were compared. RESULTS: In all, 23 of 139 breast lesions were benign. Se and Sp of DCE-MRI was 100% and 30.4% (NPV = 100%). Se and Sp of IVIM parameters in parallel were 92.2% and 52.2% (NPV = 57.1%) and for the ADC 95.7% and 17.4%, respectively (NPV = 44.4%). In all, 26 of 139 lesions were classified as BI-RADS 3 (n = 7) or BI-RADS 4 (n = 19). DCE-MRI combined with ADC (Se = 99.1%, Sp = 34.8%) or IVIM (Se = 99.1%, Sp = 56.5%) did significantly improve (P = 0.016) Sp of DCE-MRI alone for workup of BI-RADS 3 and 4 lesions (NPV = 92.9%). CONCLUSION: Quantitative DWI has a lower NPV compared to DCE-MRI for evaluation of breast lesions and may therefore not be able to replace DCE-MRI; when implemented after DCE-MRI as problem solver for BI-RADS 3 and 4 lesions, the combined specificity improves significantly. J. Magn. Reson. Imaging 2016;44:1642-1649. PMID- 27273696 TI - Platinum(II) Metallomesogens: New External-Stimuli-Responsive Photoluminescence Materials. AB - New dicatenar isoquinoline-functionalized pyrazoles, [Hpz(R(n,n)iq) ] (R(n,n)=C6 H3 (OCn H2n+1 )2 ; n=4, 6, 8, 10, 12, 14, 16, 18), have been strategically designed and synthesized to induce mesomorphic and luminescence properties into the corresponding bis(isoquinolinylpyrazolate)platinum(II) complexes [Pt(pz(R(n,n)iq) )2 ]. Thermal studies reveal that all platinum(II) compounds exhibit columnar mesophases over an exceptionally wide temperature range, above 300 degrees C in most cases. The photophysical behavior was also investigated in solution and in the solid state. As a consequence of the formation of Pt???Pt interactions, the weak greenish emission of the platinum derivatives turns bright orange in the mesophase. Additionally, the complexes are sensitive to a great variety of external inputs, such as temperature, mechanical grinding, pressure, solvents, and vapors. On this basis, they are used as dopant agents of a polyvinylpyrrolidone or poly(methyl methacrylate) polymer matrix to achieve stimuli-responsive thin films. PMID- 27273695 TI - Significant reductions in human visual gamma frequency by the gaba reuptake inhibitor tiagabine revealed by robust peak frequency estimation. AB - The frequency of visual gamma oscillations is determined by both the neuronal excitation-inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [] (Neuropsychopharmacology 38(6):1105-1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re-evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans. Hum Brain Mapp 37:3882 3896, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273698 TI - Erratum. PMID- 27273697 TI - Early Invasive Strategy for Unstable Angina: a New Meta-Analysis of Old Clinical Trials. AB - Randomized controlled trials (RCTs) were conflicting to support whether unstable angina versus non-ST-elevation myocardial infarction (UA/NSTEMI) patients best undergo early invasive or a conservative revascularization strategy. RCTs with cardiac biomarkers, in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1975-2013 were reviewed considering all cause mortality, recurrent non-fatal myocardial infarction (MI) and their combination. Follow-up lasted from 6-24 months and the use of routine invasive strategy up to its end was associated with a significantly lower composite of all-cause mortality and recurrent non-fatal MI (Relative Risk [RR] 0.79; 95% confidence interval [CI], 0.70-0.90) in UA/NSTEMI. In NSTEMI, by the invasive strategy, there was no benefit (RR 1.19; 95% CI, 1.03-1.38). In the shorter time period, from randomization to discharge, a routine invasive strategy was associated with significantly higher odds of the combined end-point among UA/NSTEMI (RR 1.29; 95% CI, 1.05-1.58) and NSTEMI (RR 1.82; 95% CI, 1.34-2.48) patients. Therefore, in trials recruiting a large number of UA patients, by routine invasive strategy the largest benefit was seen, whereas in NSTEMI patients death and non-fatal MI were not lowered. Routine invasive treatment in UA patients is accordingly supported by the present study. PMID- 27273699 TI - Erratum. PMID- 27273700 TI - Erratum. PMID- 27273702 TI - Erratum. PMID- 27273701 TI - Erratum. PMID- 27273703 TI - Early intervention for incipient insanity: early notions from the 19th century English literature. AB - AIM: Early intervention programmes in mental illnesses started to bloom in the 1990s, and many programmes have been established worldwide during the past twenty years. However, the concept of early intervention has emerged during the 19th century but it did not make much impact on practice. The aim of this review is to identify the difficulties appeared during that period of time which could provide insight into the modern development of early intervention initiatives. METHODS: A narrative review which focused on English literature about early intervention for insanity during the 19th century was undertaken. RESULTS: Clinicians during the 19th century recognized that treatment would be the most effective at the early stage of the mental illness and they had emphasized the importance of early intervention. However, because of a number of factors, such as the limited roles of asylums, lack of knowledge about mental disorder and the lack of effective treatment, the idea of early intervention did not make impact in clinical service during that period of time. CONCLUSION: During the past two hundred years, understanding towards mental illness has advanced and more effective treatments, such as the use of anti-psychotic medications, have been developed. Reflecting on the past experience and difficulties might shed light on the development of today early intervention in mental disorder. PMID- 27273704 TI - Erratum: Genetic link between renal birth defects and congenital heart disease. PMID- 27273706 TI - Long-term spatial memory in Vespula germanica social wasps: the influence of past experience on foraging behavior. AB - Social insects exhibit complex learning and memory mechanisms while foraging. Vespula germanica (Fab.) (Hymenoptera: Vespidae) is an invasive social wasp that frequently forages on undepleted food sources, making several flights between the resource and the nest. Previous studies have shown that during this relocating behavior, wasps learn to associate food with a certain site, and can recall this association 1 h later. In this work, we evaluated whether this wasp species is capable of retrieving an established association after 24 h. For this purpose, we trained free flying individuals to collect proteinaceous food from an experimental plate (feeder) located in an experimental array. A total of 150 individuals were allowed 2, 4, or 8 visits. After the training phase, the array was removed and set up again 24 h later, but this time a second baited plate was placed opposite to the first. After 24 h we recorded the rate of wasps that returned to the experimental area and those which collected food from the previously learned feeding station or the nonlearned one. During the testing phase, we observed that a low rate of wasps trained with 2 collecting visits returned to the experimental area (22%), whereas the rate of returning wasps trained with 4 or 8 collecting visits was higher (51% and 41%, respectively). Moreover, wasps trained with 8 feeding visits collected food from the previously learned feeding station at a higher rate than those that did from the nonlearned one. In contrast, wasps trained 2 or 4 times chose both feeding stations at a similar rate. Thus, significantly more wasps returned to the previously learned feeding station after 8 repeated foraging flights but not after only 2 or 4 visits. This is the first report that demonstrates the existence of long-term spatial memory in V. germanica wasps. PMID- 27273709 TI - Protocol for HER2 FISH determination on PAXgene-fixed and paraffin-embedded tissue in breast cancer. AB - Molecular diagnostics in personalized medicine increasingly relies on the combination of a variety of analytical technologies to characterize individual diseases and to select patients for targeted therapies. The gold standard for tissue-based diagnostics is fixation in formalin and embedding in paraffin, which results in excellent preservation of morphology but negatively impacts on a variety of molecular assays. The formalin-free, non-cross-linking PAXgene tissue system preserves morphology in a similar way to formalin, but also preserves biomolecules essentially in a similar way to cryopreservation, which markedly widens the spectrum, sensitivity and accuracy of molecular analytics. In this study, we have developed and tested a protocol for PAXgene-fixed and paraffin embedded tissues for fluorescent in situ hybridization (FISH). The implementation of a 24-h formalin postfixation step of slides from PAXgene-fixed and paraffin embedded tissues allowed us to use the assays approved for formalin-fixed and paraffin-embedded tissues. The equivalence of the methodologies was demonstrated by FISH analysis of HER2 amplification in breast cancer cases. The 24-h postfixation step of the slides used for FISH can be well integrated in the routine diagnostic workflow and allows the remaining PAXgene-fixed and paraffin embedded tissue to be used for further molecular testing. PMID- 27273705 TI - Voltage-gated calcium channels and their auxiliary subunits: physiology and pathophysiology and pharmacology. AB - Voltage-gated calcium channels are essential players in many physiological processes in excitable cells. There are three main subdivisions of calcium channel, defined by the pore-forming alpha1 subunit, the CaV 1, CaV 2 and CaV 3 channels. For all the subtypes of voltage-gated calcium channel, their gating properties are key for the precise control of neurotransmitter release, muscle contraction and cell excitability, among many other processes. For the CaV 1 and CaV 2 channels, their ability to reach their required destinations in the cell membrane, their activation and the fine tuning of their biophysical properties are all dramatically influenced by the auxiliary subunits that associate with them. Furthermore, there are many diseases, both genetic and acquired, involving voltage-gated calcium channels. This review will provide a general introduction and then concentrate particularly on the role of auxiliary alpha2 delta subunits in both physiological and pathological processes involving calcium channels, and as a therapeutic target. PMID- 27273710 TI - Efficacy and Safety of Salmeterol/fluticasone Combination Therapy in Infants and Preschool Children with Asthma Insufficiently Controlled by Inhaled Corticosteroids. AB - BACKGROUND: Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma. OBJECTIVES: To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 MUg/day) and fluticasone propionate (100 MUg/day), in infants and preschool children with asthma. METHODS: The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 MUg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE). RESULTS: Mean patient age was 3.1 years, and 94.2% had mild to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs. CONCLUSIONS: SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to moderate asthma in infant and preschool-aged children. PMID- 27273711 TI - Febrile Seizure Risk After Vaccination in Children 6 to 23 Months. AB - BACKGROUND AND OBJECTIVE: An increased risk of febrile seizure (FS) was identified with concomitant administration of trivalent inactivated influenza vaccine (IIV3) and pneumococcal conjugate vaccine (PCV) 13-valent during the 2010 2011 influenza season. Our objective was to determine whether concomitant administration of IIV3 with other vaccines affects the FS risk. METHODS: We examined the risk of FS 0 to 1 day postvaccination for all routinely recommended vaccines among children aged 6 through 23 months during a period encompassing 5 influenza seasons (2006-2007 through 2010-2011). We used a population-based self controlled risk interval analysis with a control interval of 14 to 20 days postvaccination. We used multivariable regression to control for receipt of concomitant vaccines and test for interaction between vaccines. RESULTS: Only PCV 7-valent had an independent FS risk (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.00 to 3.91). IIV3 had no independent risk (IRR, 0.46; 95% CI, 0.21 to 1.02), but risk was increased when IIV3 was given with either PCV (IRR, 3.50; 95% CI, 1.13 to 10.85) or a diphtheria-tetanus-acellular-pertussis (DTaP)-containing vaccine (IRR, 3.50; 95% CI, 1.52 to 8.07). The maximum estimated absolute excess risk due to concomitant administration of IIV3, PCV, and DTaP-containing vaccines compared with administration on separate days was 30 FS per 100 000 persons vaccinated. CONCLUSIONS: The administration of IIV3 on the same day as either PCV or a DTaP-containing vaccine was associated with a greater risk of FS than when IIV3 was given on a separate day. The absolute risk of postvaccination FS with these vaccine combinations was small. PMID- 27273713 TI - Vaccines and Febrile Seizures: Quantifying the Risk. PMID- 27273712 TI - Popular Music Celebrity Endorsements in Food and Nonalcoholic Beverage Marketing. AB - BACKGROUND: Food and beverage marketing has been associated with childhood obesity. We quantified the number and type of food or beverage brands promoted by music celebrities, assessed the nutritional quality of the products, and examined Teen Choice Award data to assess the celebrities' popularity among adolescents. METHODS: This was a descriptive study. A list of music celebrities associated with the 2013 and 2014 Billboard Hot 100 Chart, which ranks songs according to sales and radio impressions, was compiled. Data on celebrity endorsements were gathered from official company Web sites, YouTube commercials, an advertising database, and media reports. Nutritional quality of foods was assessed according to the Nutrient Profile Index, whereas nonalcoholic beverages were evaluated based on calories from added sugar. Teen Choice Award nominations were used to measure the celebrities' popularity among adolescents. RESULTS: Of the 590 endorsements made by the 163 celebrities in the sample, consumer goods (eg, fragrances, makeup) represented the largest endorsement category (26%), followed by food and beverage (18%) and retail (11%). Sixty-five celebrities were collectively associated with 57 different food and beverage brands owned by 38 parent companies. Of these 65 celebrities, 53 (81.5%) had >=1 Teen Choice Award nomination. Forty-nine (71%) of the 69 nonalcoholic beverage references promoted sugar-sweetened beverages. Twenty-one (80.8%) of the 26 endorsed foods were energy dense and nutrient poor. Baauer, will.i.am, Justin Timberlake, Maroon 5, and Britney Spears had the most food and beverage endorsements. CONCLUSIONS: This study demonstrates that music celebrities who are popular among adolescents endorse energy-dense, nutrient-poor products. PMID- 27273714 TI - Call rates of mothers change with maternal experience and with infant characteristics in free-ranging gray-cheeked mangabeys. AB - Studies have shown that becoming a mother triggers important social changes within females, according to both social experience and infant characteristics, showing different maternal concerns. But how this impacts call usage has been far less studied. Based on 6 months of observations of five free-ranging groups of gray-cheeked mangabeys, we investigated variations in the production of three call types (contact, excitement, and alarm calls) in 29 females of different ages, dominance ranks, and infant rearing experiences: 15 females with infants of different ages and sexes, and 14 females without infants. We found that in females with infants-both maternal and infant characteristics influenced call production in a call type-dependent way. Females produced contact calls at a higher rate during the first month of infant age and after weaning when infants start to move away. Mothers of daughters produced more contact calls than mothers of sons. More excitement calls were recorded for first-time and young mothers and for females with young infants, while alarm call rates were not influenced by any of these factors. Increased mother-infant spatial separation enhanced only contact and excitement call rates. Finally, we found that females with infants vocalized much more than females without infants. Our results contribute to the current debate about the social factors responsible for the flexibility of call usage in nonhuman primates and open new lines for research on mothering behavior in forest-dwelling species. Am. J. Primatol. 78:983-991, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273715 TI - Clinical pre-test of a computerised antithrombotic risk assessment tool for stroke prevention in atrial fibrillation patients: giving consideration to NOACs. AB - RATIONALE, AIMS AND OBJECTIVES: The decision-making around antithrombotics in atrial fibrillation requires comprehensive risk versus benefit assessment. In view of the availability of novel oral anticoagulants (NOACs) including dabigatran, rivaroxaban and apixaban, a decision support tool designed to assist the selection of antithrombotics has been modified to consider both warfarin and NOACs. This study aims to pre-test this modified decision support tool. METHODS: The decision support tool was modified to consider either warfarin or NOACs as first-line therapy and applied to data pertaining to a cohort of 393 patients in New South Wales. RESULTS: Overall, 380 (96.7%) patients were eligible for oral anticoagulants. In the scenario of warfarin being recommended as first-line therapy, the Computerised Antithrombotic Risk Assessment Tool version 2.0 (caratv2.0) recommended warfarin for 360 (91.6%) patients, any NOAC for 5 (1.3%) patients, either rivaroxaban or apixaban for 6 (1.5%) patients and apixaban for 9 (2.2%) patients. In the scenario of NOACs as first-line therapy, caratv2.0 recommended any NOAC for 279 (70.9%) patients, either rivaroxaban or apixaban for 80 (20.4%) patients, apixaban for 9 (2.3%) patients and warfarin for 12 (3.1%) patients. Key reasons for caratv2.0 to recommend a change from warfarin (patients' current therapy) to NOACs included known warfarin allergy/adverse reaction, a history of intracranial bleeding, and previous gastrointestinal bleeding. Key predictors for caratv2.0 to consider that patients are more suitable for NOACs over warfarin were a diagnosis of other gastrointestinal diseases, more co-morbidities and high risk of falls. CONCLUSIONS: According to this decision support tool, both warfarin and NOACs are viable treatment options in majority of the patients, but there is a scope for better rationalization of therapy. PMID- 27273716 TI - Motion Responses in Human Strabismus: What Optokinesis in the Deviating Eye Is Telling Us. PMID- 27273717 TI - Author Response: Motion Responses in Human Strabismus: What Optokinesis in the Deviating Eye Is Telling Us. PMID- 27273719 TI - Influence of Ametropia and Its Correction on Measurement of Accommodation. AB - PURPOSE: Amplitude of accommodation (AA) is reportedly greater for myopic eyes than for hyperopic eyes. We investigated potential explanations for this difference. METHODS: Analytical analysis and computer ray tracing were performed on two schematic eye models of axial ametropia. Using paraxial and nonparaxial approaches, AA was specified for the naked and the corrected eye using the anterior corneal surface as the reference plane. RESULTS: Assuming that axial myopia is due entirely to an increase in vitreous chamber depth, AA increases with the amount of myopia for two reasons that have not always been taken into account. First is the choice of reference location for specifying refractive error and AA in diopters. When specified relative to the cornea, AA increases with the degree of myopia more than when specified relative to the eye's first Gaussian principal plane. The second factor is movement of the eye's second Gaussian principal plane toward the retina during accommodation, which has a larger dioptric effect in shorter eyes. CONCLUSIONS: Using the corneal plane (placed at the corneal vertex) as the reference plane for specifying accommodation, AA depends slightly on the axial length of the eye's vitreous chamber. This dependency can be reduced significantly by using a reference plane located 4 mm posterior to the corneal plane. A simple formula is provided to help clinicians and researchers obtain a value of AA that closely reflects power changes of the crystalline lens, independent of axial ametropia and its correction with lenses. PMID- 27273718 TI - Hydrogen Sulfide Contributes to Retinal Neovascularization in Ischemia-Induced Retinopathy. AB - PURPOSE: Hydrogen sulfide (H2S) is an endogenous gaseous signaling molecule with significant pathophysiological importance, but its role in retinal neovascular diseases is unknown. Hydrogen sulfide is generated from L-cysteine by cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE), and/or 3 mercaptopyruvate sulfurtransferase (3-MST). The aim of this study was to investigate the role of H2S in retinal neovascularization (NV) in ischemia induced retinopathy. METHODS: Studies were performed in a murine model of oxygen induced retinopathy (OIR). Hydrogen sulfide was detected with a fluorescent assay. Western blots and immunohistochemistry were used to assess the changes of H2S-producing enzymes. Gene deletion and pharmacologic inhibition were used to investigate the role of H2S in retinal NV. RESULTS: Hydrogen sulfide production was markedly increased in retinas from OIR mice compared with those from room air (RA) controls. Cystathionine-beta-synthase and CSE were significantly increased in OIR retinas, whereas 3-MST was not changed. Cystathionine-beta-synthase was expressed throughout the neuronal retina and upregulated in neurons and glia during OIR. Cystathionine-gamma-lyase was also localized to multiple retinal layers. Its immunoreactivity was prominently increased in neovascular tufts in OIR. Pharmacologic inhibition of CBS/CSE or genetic deletion of CSE significantly reduced retinal NV in OIR. CONCLUSIONS: Our data indicate that the H2S-generating enzymes/H2S contributes to retinal NV in ischemia-induced retinopathy and suggest that blocking this pathway may provide novel therapeutic approaches for the treatment of proliferative retinopathy. PMID- 27273721 TI - Spectral-Domain Optical Coherence Tomography Features in Open-Angle Glaucoma With Diabetes Mellitus and Inadequate Glycemic Control. AB - PURPOSE: To evaluate spectral-domain optical coherence tomography (SD-OCT) features according to glycemic control status in open-angle glaucoma with diabetes mellitus. METHODS: Subjects underwent comprehensive ocular examination, visual field testing, and SD-OCT imaging (Cirrus HD-OCT). The relationship between glycosylated hemoglobin (HbA1c) and OCT measurements was compared between diabetic nonglaucomatous eyes and diabetic glaucomatous eyes. Glaucoma discriminating ability was assessed using the area under the receiver operating characteristic curves (AUCs) for OCT parameters and compared between groups relative to the glycemic control group. RESULTS: Analysis was performed on 69 nonglaucomatous and 87 glaucomatous eyes in the nondiabetic group, and on 72 nonglaucomatous and 56 glaucomatous eyes in the diabetic group. Average, inferonasal, inferior, and inferotemporal ganglion cell-inner plexiform layer (GCIPL) thicknesses were positively correlated with HbA1c in diabetic nonglaucomatous eyes (P = 0.040, 0.037, 0.025, and 0.013, respectively). The AUC of the average cup-to-disc area ratio (CDR), vertical CDR, and cup volume in diabetic eyes with poor glycemic control was significantly higher than those in nondiabetic eyes (P = 0.011, 0.003, and 0.043, respectively). The AUC of cube volume, cube average thickness, and minimal GCIPL thickness in diabetic eyes with poor glycemic control was lower than those in nondiabetic eyes (P = 0.006, 0.007, and 0.004, respectively). CONCLUSIONS: In this study, optic nerve head parameters had a superior ability to discriminate glaucoma in diabetic eyes with poor glycemic control. Conversely, the ability to discriminate glaucoma using macular parameters tended to be lower for diabetic eyes with inadequate glycemic control. PMID- 27273722 TI - Hierarchical networks of redox-active reduced crumpled graphene oxide and functionalized few-walled carbon nanotubes for rapid electrochemical energy storage. AB - Crumpled graphene is known to have a strong aggregation-resistive property due to its unique 3D morphology, providing a promising solution to prevent the restacking issue of graphene based electrode materials. Here, we demonstrate the utilization of redox-active oxygen functional groups on the partially reduced crumpled graphene oxide (r-CGO) for electrochemical energy storage applications. To effectively utilize the surface redox reactions of the functional groups, hierarchical networks of electrodes including r-CGO and functionalized few-walled carbon nanotubes (f-FWNTs) are assembled via a vacuum-filtration process, resulting in a 3D porous structure. These composite electrodes are employed as positive electrodes in Li-cells, delivering high gravimetric capacities of up to ~170 mA h g(-1) with significantly enhanced rate-capability compared to the electrodes consisting of conventional 2D reduced graphene oxide and f-FWNTs. These results highlight the importance of microstructure design coupled with oxygen chemistry control, to maximize the surface redox reactions on functionalized graphene based electrodes. PMID- 27273720 TI - Safety and Feasibility of Quantitative Multiplexed Cytokine Analysis From Office Based Vitreous Aspiration. AB - PURPOSE: The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis. METHODS: Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitreous cytokine concentrations in a subset of patients with diabetic macular edema (DME) were analyzed using a 42 plex-cytokine bead array. These results were compared with vitreous cytokine concentrations in proliferative diabetic retinopathy (PDR) and controls (macular hole, epiretinal membrane, symptomatic vitreous floaters) from pars plana vitrectomy. RESULTS: An adequate volume of vitreous fluid (100-200 MUL) was obtained in 52 (88%) of 59 office based sampling attempts. The average length of follow-up was 300 days (range, 42 926 days). There were no complications, including cataract, retinal tear or detachment, and endophthalmitis. Two patients (3%) had posterior vitreous detachments within 3 months. Vitreous cytokine concentrations were measured in 44 patients: 14 controls, 13 with DME, and 17 with PDR. The concentration of ADAM11, CXCL-10, IL-8, and PDGF-A were higher in PDR compared with controls and DME. The concentration of IL-6 was higher in PDR compared with controls, but not compared with DME. CONCLUSIONS: Office-based vitreous aspiration is safe and yields high quality samples for multiplex vitreous cytokine analysis. Significant elevations of vitreous cytokines were found in PDR compared with DME and controls, including the novel finding of elevated ADAM11. As such, office-based aspiration is a safe and effective means to identify vitreous factors associated with vitreoretinal disease. PMID- 27273723 TI - Pain and concomitant symptoms in medical and elective surgical inpatients: a point prevalence survey. AB - AIMS AND OBJECTIVES: This study (1) reports the prevalence of severe pain and other symptoms among both medical and elective surgical patients and (2) examines the co-occurrence of severe pain and other symptoms and symptom-related distress. BACKGROUND: As symptom burden can interfere with patients' rehabilitation, daily activities and quality of life, detection and optimal management of pain and other symptoms is important for good nursing care. DESIGN: Cross-sectional point prevalence survey. METHODS: Data were collected by self-report on 10 predetermined screening days from medical and surgical patients admitted to a local hospital in Oslo, Norway. Patients rated their average level of pain on movement during the last 24 hours on a 0-10 numeric rating scale (severe pain defined as >=7). The occurrence of other symptoms and symptom distress were measured with 15 items from the Memorial Symptom Assessment Scale. Data on comorbidities were also collected. RESULTS: A total of 602 patients participated in the study (response rate = 71%). Medical patients had a higher incidence of symptoms than surgical patients and reported more symptom distress. Surgical patients reported higher levels of pain than medical patients, but the prevalence of severe pain did not differ between the two groups. In analyses adjusted for age, sex and comorbidities, severe pain among medical patients was associated with severe distress due to concentration difficulties, vomiting, itching and swelling, while severe pain among surgical patients was associated with the occurrence of drowsiness. CONCLUSION: Associations between severe pain and other symptoms differ for medical and elective surgical patients. RELEVANCE TO CLINICAL PRACTICE: Knowledge of concurrent symptoms and comorbidities in medical and surgical patients experiencing severe pain may help nurses to better tailor management of the patients' symptoms and improve quality of care. PMID- 27273724 TI - Germline development in amniotes: A paradigm shift in primordial germ cell specification. AB - In the field of germline development in amniote vertebrates, primordial germ cell (PGC) specification in birds and reptiles remains controversial. Avians are believed to adopt a predetermination or maternal specification mode of PGC formation, contrary to an inductive mode employed by mammals and, supposedly, reptiles. Here, we revisit and review some key aspects of PGC development that channelled the current subdivision, and challenge the position of birds and reptiles as well as the 'binary' evolutionary model of PGC development in vertebrates. We propose an alternative view on PGC specification where germ plasm plays a role in laying the foundation for the formation of PGC precursors (pPGC), but not necessarily of PGCs. Moreover, inductive mechanisms may be necessary for the transition from pPGCs to PGCs. Within this framework, the implementation of data from birds and reptiles could provide new insights on the evolution of PGC specification in amniotes. PMID- 27273725 TI - Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30-year nationwide cohort of 1478 patients under 18 years of age. AB - The French national cohort of children with Langerhans cell histiocytosis (LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15-year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ (RO+) was treated with cladribine and cytarabine. A total of 483 (33%) patients were enrolled before 1998, and 995 (67%) after 1998. Five-year survival was 96.6% (95% confidence interval: 95.4-97.5%) overall, improving from 92% pre 1998 to 99% post-1998 (P < 0.001 adjusted to disease extent). This change was supported by an increase in 5-year survival from 60% to 92% in the RO+ group. Survival was particularly associated with cladribine and cytarabine among refractory RO+ patients. Disease reactivation was slightly less frequent after 1998, due to better enrolment of single-system patients, extended therapy duration, and more efficient second-line therapy. The crude rates of endocrine and neurological sequelae (the most frequent sequelae) appeared to improve over time, but this difference was not observed when the analysis was stratified by disease extent. PMID- 27273726 TI - Facial-nerve regeneration ability of a hybrid artificial nerve conduit containing uncultured adipose-derived stromal vascular fraction: An experimental study. AB - PURPOSE: This study investigated the potential of uncultured-stromal-vascular fraction (SVF) cells in promoting facial nerve regeneration in a rat model. MATERIALS AND METHODS: A 7-mm nerve defect was created in the buccal branch of facial nerve in five groups of Lewis rats (total n = 30, n = 6 per group). A silicone tube, infused with syngeneic uncultured-SVF was implanted into the facial nerve defect. Groups 1-3 received 1 * 103 , 1 * 105 , and 1 * 107 cells, and regenerated nerves were examined at 13 weeks after the surgery. The findings were compared to the autograft and collagen-alone groups with facial palsy score (FPS), the number of myelinated fibers, fiber diameter, axon diameter, myelin thickness, and g ratio. RESULTS: There was no significant difference in FPS between the autograft and 1 * 105 -cell groups at 13 weeks after surgery, and FPS values of these two groups were significantly higher than those of the other three groups (P < 0.01). Axon diameter significantly increased in the 1 * 105 cell group compared with the 1 * 103 - (P < 0.05) and 1 * 107 -cell groups (P < 0.01). Myelin thickness was found to be the highest in the autograft group, followed by the 1 * 105 -, 1 * 103 -, 1 * 107 -cell, and negative control groups, and there were significant differences among all groups (P < 0.01). CONCLUSION: The infusion of uncultured-SVF into the artificial nerve conduit promoted optimal nerve regeneration that was significantly better than nerve conduit alone. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:808-818, 2017. PMID- 27273727 TI - Modified PEEK Resin Bonded Fixed Dental Prosthesis for a Young Cleft Lip and Palate Patient. AB - OBJECTIVE: This clinical report presents the use of a modified poly ether-ether ketone material as an alternative material for the fabrication of resin-bonded fixed dental prosthesis (RBFDP) framework. This new material can be used for patients allergic to metals, maintaining the same high esthetic demand of ceramics, presenting light weightness and a flexibility similar to bone as a distinct advantage over ceramic materials. CONCLUSIONS: The use of a BioHPP RBFDP framework could be considered as an alternative restoration for the replacement of missing lateral incisors in young patients with cleft palate defects. CLINICAL SIGNIFICANCE: This modified PEEK material known as BioHPP, is a biocompatible, non allergic, rigid material with good mechanical properties, wear resistance, chemical stability, high polishing and low absorption properties. BioHPP frameworks can be manufactured either via CAD/CAM or via the conventional lost wax technique. The low modulus of elasticity, combined with the use of indirect composite resin as a veneering material, provide a distinct advantage over ceramics or metal ceramics on dampening the occlusal forces, reducing the risk of debonding. (J Esthet Restor Dent 28:201-207, 2016). PMID- 27273728 TI - Scanning electron microscopy combined with image processing technique: Analysis of microstructure, texture and tenderness in Semitendinous and Gluteus Medius bovine muscles. AB - In this study the effect of freeze drying on the microstructure, texture, and tenderness of Semitendinous and Gluteus Medius bovine muscles were analyzed applying Scanning Electron Microscopy combined with image analysis. Samples were analyzed by Scanning Electron Microscopy at different magnifications (250, 500, and 1,000*). Texture parameters were analyzed by Texture analyzer and by image analysis. Tenderness by Warner-Bratzler shear force. Significant differences (p < 0.05) were obtained for image and instrumental texture features. A linear trend with a linear correlation was applied for instrumental and image features. Image texture features calculated from Gray Level Co-occurrence Matrix (homogeneity, contrast, entropy, correlation and energy) at 1,000* in both muscles had high correlations with instrumental features (chewiness, hardness, cohesiveness, and springiness). Tenderness showed a positive correlation in both muscles with image features (energy and homogeneity). Combing Scanning Electron Microscopy with image analysis can be a useful tool to analyze quality parameters in meat.Summary SCANNING 38:727-734, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273729 TI - In Vivo Development of Transplant Arteriosclerosis in Humanized Mice Reflects Alloantigen Recognition and Peripheral Treg Phenotype of Lung Transplant Recipients. AB - Experimentally, regulatory T cells inhibit rejection. In clinical transplantations, however, it is not known whether T cell regulation is the cause for, or an epiphenomenon of, long-term allograft survival. Here, we study naive and alloantigen-primed T cell responses of clinical lung transplant recipients in humanized mice. The pericardiophrenic artery procured from human lung grafts was implanted into the aorta of NODrag-/- /IL-2rgammac-/- mice reconstituted with peripheral blood mononuclear cells (PBMCs) from the respective lung recipient. Naive or primed allogeneic PBMCs procured 21 days post-lung transplantation with or without enriching for CD4+ CD25high T cells were used. Transplant arteriosclerosis was assessed 28 days later by histology. Mice reconstituted with alloantigen-primed PBMCs showed significantly more severe transplant arteriosclerosis than did mice with naive PBMCs (p = 0.005). Transplant arteriosclerosis was equally suppressed by enriching for autologous naive (p = 0.012) or alloantigen-primed regulatory T cells (Tregs) (p = 0.009). Alloantigen priming in clinical lung recipients can be adoptively transferred into a humanized mouse model. Transplant arteriosclerosis elicited by naive or alloantigen-primed PBMCs can be similarly controlled by potent autologous Tregs. Cellular therapy with expanded autologous Tregs in lung transplantation might be a promising future strategy. PMID- 27273730 TI - Interactions of nitric oxide with alpha2 -adrenoceptors within the locus coeruleus underlie the facilitation of inhibitory avoidance memory by agmatine. AB - BACKGROUND AND PURPOSE: Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for alpha-adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically involved in learning and memory processes. EXPERIMENTAL APPROACH: The hippocampus and LC of male Wistar rat were stereotaxically cannulated for injection. Effects of agmatine, given i.p. or intra-LC, on acquisition, consolidation and retrieval of inhibitory avoidance (IA) memory were measured. The NO donor S-nitrosoglutathione, non-specific (L-NAME) and specific NOS inhibitors (L-NIL, 7-NI, L-NIO), the alpha2 -adrenoceptor antagonist (yohimbine) or the corresponding agonist (clonidine) were injected intra-LC before agmatine. Intra-hippocampal injections of the NMDA antagonist, MK-801 (dizocilpine), were used to modify the memory enhancing effects of agmatine, SNG and yohimbine. Expression of tyrosine hydroxylase (TH) and eNOS in the LC was assessed immunohistochemically. KEY RESULTS: Agmatine (intra-LC or i.p.) facilitated memory retrieval in the IA test. S-nitrosoglutathione potentiated, while L-NAME and L-NIO decreased, these effects of agmatine. L-NIL and 7-NI did not alter the effects of agmatine. Yohimbine potentiated, whereas clonidine attenuated, effects of agmatine within the LC. The effects of agmatine, S-nitrosoglutathione and yohimbine were blocked by intra-hippocampal MK-801. Agmatine increased the population of TH- and eNOS-immunoreactive elements in the LC. CONCLUSIONS AND IMPLICATIONS: The facilitation of memory retrieval in the IA test by agmatine is probably mediated by interactions between eNOS, NO and noradrenergic pathways in the LC. PMID- 27273731 TI - Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. AB - IMPORTANCE: An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden. OBJECTIVE: To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin. DESIGN, SETTING, AND PARTICIPANTS: This clinical trial was a double blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5%-11.0%) using more than 1.5 U/kg/d of insulin. INTERVENTIONS: Subcutaneous injection of liraglutide (1.8 mg/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures. RESULTS: Among 71 patients, 45 (63%) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0% (1.2%) to 7.9% (1.1%) in the liraglutide group (P < .001) and remained unchanged (8.9%) in the placebo group, with an estimated treatment difference of 0.9% (95% CI, -1.5 to -0.4) (P = .002). Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of -2.3 kg (95% CI, -4.3 to -0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5% (95% CI, -21.8% to -1.1%) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group. CONCLUSIONS AND RELEVANCE: Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01505673. PMID- 27273732 TI - Brief Report: Trends in Hospitalizations Due to Acute Coronary Syndromes and Stroke in Patients With Systemic Lupus Erythematosus, 1996 to 2012. AB - OBJECTIVE: Cardiovascular disease (CVD) has been recognized as a major cause of morbidity in patients with systemic lupus erythematosus (SLE), but it is not clear whether increased awareness of these risks has translated into improvements in CVD morbidity at the population level. The aim of this study was to examine trends in hospitalization rates for CVD events in a representative sample of adult patients with SLE in the US from 1996 to 2012. METHODS: We used the Nationwide Inpatient Sample to estimate the rates of hospitalization for acute myocardial infarction (MI), unstable angina, and ischemic stroke from 1996 to 2012 in patients with SLE. We compared these trends with those in the general population. RESULTS: During the study years, there were an estimated 31,012 hospitalizations for acute MI, 4,160 hospitalizations for unstable angina, and 26,144 hospitalizations for ischemic stroke among patients with SLE. The rates of hospitalization for acute MI and ischemic stroke increased over time in patients with SLE, while the rates for unstable angina decreased. The rates for all 3 conditions decreased in the general population over these years, with hospitalization rates for unstable angina decreasing faster in the general population than in patients with SLE. CONCLUSION: Increased awareness of the burden of CVD in patients with SLE has not yet translated into decreased rates of hospitalization for acute MI or stroke. This may be due to barriers in implementation of CVD risk factor modification or to SLE-specific risks that have not yet been identified or effectively targeted. PMID- 27273733 TI - Impact of sugars and sugar taxation on body weight control: A comprehensive literature review. AB - OBJECTIVE: To conduct a comprehensive literature review in the field of added sugar consumption on weight gain including the effect of fructose-containing caloric sweeteners and sugar taxation. METHODS: A search of three databases was conducted in the time period from the inception of the databases to August 2015. Sensitive search strategies were used in order to retrieve systematic reviews (SR) of fructose, sucrose, or sugar-sweetened beverages (SSBs) on weight gain and metabolic adverse effects, conducted on humans and written in English, Spanish, or French. In addition, a review about SSB taxation and weight outcomes was conducted. RESULTS: The search yielded 24 SRs about SSBs and obesity, 23 SRs on fructose or SSBs and metabolic adverse effects, and 24 studies about SSB taxation and weight control. CONCLUSIONS: The majority of SRs, especially the most recent ones, with the highest quality and without any disclosed conflict of interest, suggested that the consumption of SSBs is a risk factor for obesity. The effect of fructose-containing caloric sweeteners, on weight gain is mediated by overconsumption of beverages with these sweeteners, leading to an extra provision of energy intake. The tax tool alone on added sugars appears insufficient to curb the obesity epidemic, but it needs to be included in a multicomponent structural strategy. PMID- 27273734 TI - Predicting pressure-dependent unimolecular rate constants using variational transition state theory with multidimensional tunneling combined with system specific quantum RRK theory: a definitive test for fluoroform dissociation. AB - Understanding the falloff in rate constants of gas-phase unimolecular reaction rate constants as the pressure is lowered is a fundamental problem in chemical kinetics, with practical importance for combustion, atmospheric chemistry, and essentially all gas-phase reaction mechanisms. In the present work, we use our recently developed system-specific quantum RRK theory, calibrated by canonical variational transition state theory with small-curvature tunneling, combined with the Lindemann-Hinshelwood mechanism, to model the dissociation reaction of fluoroform (CHF3), which provides a definitive test for falloff modeling. Our predicted pressure-dependent thermal rate constants are in excellent agreement with experimental values over a wide range of pressures and temperatures. The present validation of our methodology, which is able to include variational transition state effects, multidimensional tunneling based on the directly calculated potential energy surface along the tunneling path, and torsional and other vibrational anharmonicity, together with state-of-the-art reaction-path based direct dynamics calculations, is important because the method is less empirical than models routinely used for generating full mechanisms, while also being simpler in key respects than full master equation treatments and the full reduced falloff curve and modified strong collision methods of Troe. PMID- 27273735 TI - Risk Factors for In-Hospital Mortality in Heart Failure Patients: Does Rurality, Payer or Admission Source Matter? AB - PURPOSE: Considering the high prevalence of heart failure and the economic burden of the disease, factors that influence in-hospital mortality are of importance in improving outcomes of care for this patient population. The purpose of this study was to examine the determinants of in-hospital mortality for adult heart failure patients. METHODS: The study design is a retrospective observational study design using the 2010 Nebraska Hospital Discharge data set including 4,319 hospitalizations for 3,521 heart failure patients admitted to 79 hospitals in Nebraska. Hierarchical logistic regression models including patient- and hospital specific random intercepts were analyzed. Covariates included in the analysis were patient age in years, gender, comorbidity status, length of stay, primary payer, type and source of admission, transfers, and rurality of county of residence. RESULTS: Overall, 3.5% of heart failure patients died during their hospital stay. In logistic regression analysis that adjusted for age, sex, and comorbidities, the odds of dying in hospital for heart failure patients increased with age (OR = 1.03, 95% CI: 1.01-1.04), co-morbidity (OR = 1.15; 95% CI: 1.05 1.25) and length of stay (OR = 1.03, 95% CI: 1.01-1.05). The patient's gender, payer source, rurality of county of residence, source, and type of admission were not risk factors for in-hospital death. CONCLUSION: Increasing age, comorbidity and length of stay were risk factors for in-hospital death for heart failure. An understanding of the risk factors for in-hospital death is critical to improving outcomes of care for heart failure patients. PMID- 27273736 TI - Prodromal Parkinson's disease as defined per MDS research criteria in the general elderly community. AB - BACKGROUND: Recently, the International Parkinson and Movement Disorder Society has defined research criteria for prodromal Parkinson's disease (PD), but to date their predictive value has not yet been tested in population-based cohorts. METHODS: We retrospectively applied these criteria to the longitudinal Bruneck Study cohort aged 55-94 years using recorded data on all included risk and prodromal markers that are quick and easily assessable. RESULTS: After excluding participants with idiopathic PD or secondary parkinsonism, prevalence of probable prodromal PD in the remaining 539 participants was 2.2% (95% confidence interval, 1.2%-3.9%). Of 488 participants followed up over 5 years, 11 developed incident PD. Sensitivity of "probable prodromal PD" status for incident PD was 54.6% (95% confidence interval, 28.0%-78.8%), specificity was 99.2% (97.8%-99.8%), positive predictive value was 60.0% (31.2%-83.3%), and negative predictive value was 99.0% (97.5%-99.6%). CONCLUSIONS: Our findings suggest that the new research criteria for prodromal PD are a promising tool to identify cases of incident PD over 5 years, arguing for their usefulness in defining target populations for disease prevention trials. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27273739 TI - Cofactor squelching: Artifact or fact? AB - Cofactor squelching is the term used to describe competition between transcription factors (TFs) for a limited amount of cofactors in a cell with the functional consequence that TFs in a given cell interfere with the activity of each other. Since cofactor squelching was proposed based primarily on reporter assays some 30 years ago, it has remained controversial, and the idea that it could be a physiologically relevant mechanism for transcriptional repression has not received much support. However, recent genome-wide studies have demonstrated that signal-dependent TFs are very often absent from the enhancers that are acutely repressed by those signals, which is consistent with an indirect mechanism of repression such as squelching. Here we review these recent studies in the light of the classical studies of cofactor squelching, and we discuss how TF cooperativity in so-called hotspots and super-enhancers may sensitize these to cofactor squelching. PMID- 27273737 TI - Hepatocellular carcinoma cell lines retain the genomic and transcriptomic landscapes of primary human cancers. AB - Hepatocellular carcinoma (HCC) cell lines are useful in vitro models for the study of primary HCCs. Because cell lines acquire additional mutations in culture, it is important to understand to what extent HCC cell lines retain the genetic landscapes of primary HCCs. Most HCC cell lines were established during the last century, precluding comparison between cell lines and primary cancers. In this study, 9 Chinese HCC cell lines with matched patient-derived cells at low passages (PDCs) were established in the defined culture condition. Whole genome analyses of 4 HCC cell lines showed that genomic mutation landscapes, including mutations, copy number alterations (CNAs) and HBV integrations, were highly stable during cell line establishment. Importantly, genetic alterations in cancer drivers and druggable genes were reserved in cell lines. HCC cell lines also retained gene expression patterns of primary HCCs during in vitro culture. Finally, sequential analysis of HCC cell lines and PDCs at different passages revealed their comparable and stable genomic and transcriptomic levels if maintained within proper passages. These results show that HCC cell lines largely retain the genomic and transcriptomic landscapes of primary HCCs, thus laying the rationale for testing HCC cell lines as preclinical models in precision medicine. PMID- 27273740 TI - Familial frontal fibrosing alopecia treated with dutasteride, minoxidil and artificial hair transplantation. AB - A 46-year-old premenopausal woman presented with familial frontal fibrosis alopecia affecting the temples bilaterally. The diagnosis was confirmed histologically. Her past history included rheumatoid arthritis treated with hydroxychloroquine 400 mg daily and methotrexate 20 mg weekly. Serial intralesional injections of triamcinolone did not limit the progression of hair loss. Treatment with dutasteride 0.1 mg daily and minoxidil 1 mg daily stabilised hair loss and artificial fibre hair transplantation initially led to a satisfactory cosmetic outcome. Unfortunately, the patient developed implant folliculitis uncontrolled by antibiotics, necessitating the removal of the fibres 12 months post-transplantation. PMID- 27273742 TI - An efficient approach to construct benzisothiazol-3(2H)-ones via copper-catalyzed consecutive reaction of 2-halobenzamides and carbon disulfide. AB - An efficient copper-catalyzed reaction for the synthesis of benzisothiazol-3(2H) ones has been developed, starting from easily available 2-halobenzamides and carbon disulfide, which gave the corresponding target products in 30-89% yield for 25 examples. The reaction proceeds via a consecutive process with S-C bond and S-N bond formation. PMID- 27273741 TI - Tautomers of a Fluorescent G Surrogate and Their Distinct Photophysics Provide Additional Information Channels. AB - Thienoguanosine ((th) G) is an isomorphic nucleoside analogue acting as a faithful fluorescent substitute of G, with respectable quantum yield in oligonucleotides. Photophysical analysis of (th) G reveals the existence of two ground-state tautomers with significantly shifted absorption and emission wavelengths, and high quantum yield in buffer. Using (TD)-DFT calculations, the tautomers were identified as the H1 and H3 keto-amino tautomers. When incorporated into the loop of (-)PBS, the (-)DNA copy of the HIV-1 primer binding site, both tautomers are observed and show differential sensitivity to protein binding. The red-shifted H1 tautomer is strongly favored in matched (-)/(+)PBS duplexes, while the relative emission of the H3 tautomer can be used to detect single nucleotide polymorphisms. These tautomers and their distinct environmental sensitivity provide unprecedented information channels for analyzing G residues in oligonucleotides and their complexes. PMID- 27273743 TI - Seasonality of reproductive events and early mortality in a colony of hamadryas baboons (Papio hamadryas hamadryas) over a 30-year period: Capital breeding and life history patterns in a food-provisioned population seasonally thermally stressed. AB - In environments where energy demands and resource availability vary seasonally, individuals are expected to time the optimal allocation of resources to support survival and reproduction. Although female baboons are regarded as all year round, capital breeders, we wondered how they would respond in an ecological scenario where food were not limiting, foraging effort were negligible, and they were thermally stressed during the cold winter. This study analyzes a 30-year database of conceptions, births, resumptions of postlactational ovarian activity, menarches, and prenatal and early postnatal reproductive failures recorded in a food-provisioned colony of hamadryas baboons located in a temperate zone (40 degrees 25'N) to search for seasonal patterns in their life-history patterns and explore its fitness consequences. The results show that the study females exhibited moderate seasonality and behaved like capital breeders; ovarian activity peaked during the period of benign weather conditions (spring and early summer) and births and lactation peaked during the period when they were thermally stressed and faced a negative energy balance (winter). Mistimed conceptions were more likely to fail than timed conceptions were, although this association could be artefactual due to the difficulty to accurately detect prenatal losses. Insolation and, to a lesser extent, temperature were positively associated with conceptions, resumptions of postlactational ovarian activity and onsets of menarche, and negatively associated with births. These findings highlight the extent of plasticity (width of peaks) and resiliency (retention of a capital breeding tactic even under highly seasonally thermally stressful cold conditions) in how primates can adjust their life history patterns and solve tradeoffs in a scenario of strong seasonal variation. Am. J. Primatol. 78:1149 1164, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273745 TI - Low coordinate iron derivatives stabilized by a beta-diketiminate mimic. Synthesis and coordination chemistry of enamidophosphinimine scaffolds to generate diiron dinitrogen complexes. AB - In an effort to mimic N-diaryl-beta-diketiminate ligands (Nacnac), we have converted N-arylimine phosphine ligands to enamine-phosphinimines via the Staudinger reaction. By varying the aryl azide, one can access enamine phosphinimine ligands with the same or different N-aryl substituents on both the enamine and phosphinimine units, which allows this intrinsically unsymmetrical bidentate donor set to present variable steric effects at the metal center. The enamine-phosphinimine was deprotonated and used in metathetical reactions with Fe(ii) bromide precursors to generate low coordinate complexes of the empirical formula [(CY5)NpN(Ar,Ar')]FeBr (where CY5 = cyclopentenyl; Ar,Ar' = 2,6 diisopropylphenyl, 2,6-dimethylphenyl, 2,4,6-trimethylphenyl). Depending on the substituents, these bromide derivatives can be monomeric or dimeric via bromide bridges. Reduction under dinitrogen using potassium graphite generates the dinitrogen complexes ([(CY5)NpN(Ar,Ar')]Fe)2(MU-N2) for Ar,Ar' = 2,6 diisopropylphenyl, and Ar = 2,6-dimethylphenyl, Ar' = 2,4,6-trimethylphenyl. However, for the former, a unsymmetrical side product can be isolated that has a bridging N-2,6-diisopropylphenylimide unit with one enamido-phosphine ligand bound to one iron and the other iron stabilized with an intact enamido phosphinimine. When the steric bulk is reduced on both nitrogen donors, a complicated product mixture is obtained after reduction from which a small amount of [(CY5)NpN(Ar,Ar')]Fe[(CY5)NP(Ar)] (Ar,Ar' = 2,6-dimethylphenyl) could be isolated. All of these complexes are paramagnetic and have been characterized by elemental analysis, magnetic studies and X-ray crystallography. PMID- 27273744 TI - The effect of missing KIR ligands, activating KIR genotype and haplotype on the outcome of T-cell-replete hematopoietic stem cell transplantation from HLA identical siblings in Thai patients. AB - This study was a retrospective analysis of Thai patients undergoing T-replete hematopoietic stem cell transplant from human leukocyte antigen (HLA)-identical sibling donors. We investigated 66 patients, including 40 patients with acute myeloid leukemia (AML), 12 patients with acute lymphoblastic leukemia and 14 patients with chronic myeloid leukemia. Killer cell immunoglobulin-like receptor (KIR) genes and HLA ligands were typed by polymerase chain reaction-sequence specific oligonucleotide probes. We analyzed the effect of the number of missing KIR ligands (Bw4, C1 and C2) on clinical outcomes. A beneficial effect of missing KIR ligand was not observed in both univariate and multivariate analysis. When we analyzed the effect of specific missing KIR ligand on clinical outcomes, there was a trend that patients with missing A11 ligand had lower relapse rate (P = 0.076). Therefore, we also conducted the analysis by including the group with missing KIR ligands of Bw4, C1, C2 and A11. Patients with two or more than two missing KIR ligands had a trend for better clinical outcome including reduced relapse (P = 055) and statistically significant in terms of reduced acute graft vs-host disease (aGVHD) rate (P = 0.013). In multivariate analysis, patients with two or more than two missing KIR ligands had a statistically significant better clinical outcome in terms of reduced aGVHD rate (HR = 0.155, 95%CI = 0.040-0.605, P = 0.007). The association between clinical outcome with KIR haplotypes, centromeric B haplotype and activating KIR was not observed here. Although the sample size in this study is rather limited, these data can later be subjected to meta-analysis to help reach the conclusion of the usefulness of this additional promising KIR genotyping in various hematopoietic stem cell transplantation types. PMID- 27273746 TI - Quality of life, unmet needs, and iatrogenic injuries in rehabilitation of patients with Ehlers-Danlos Syndrome hypermobility type/Joint Hypermobility Syndrome. AB - Ehlers-Danlos Syndrome, hypermobility type (EDS-HT) and the joint hypermobility syndrome (JHS) are connective tissue disorders that form an overlapping clinical syndrome and are associated with frequent medical visits and substantial morbidity. EDS-HT/JHS-associated pain correlates with poor quality of life. While physical therapy is the recommended treatment for EDS-HT/JHS, little is known about therapy-related patient experiences and iatrogenic injuries. We studied 38 adult EDS-HT/JHS patients, eliciting health-related quality of life (HRQoL) from 28 patients through the RAND SF-36 questionnaire. We also explored physical therapy experiences through focus groups with 13 patients. Our patients displayed poor HRQoL, with 71% reporting worse health over the past year. SF-36 scores were significantly lower than the scores of the average American population (P < 0.001 for 8 of 10 categories assessed), but were comparable to EDS-HT/JHS populations in Belgium, the Netherlands, Sweden, and Italy. Focus groups identified factors associated with: negative past physical therapy experiences, iatrogenic joint injuries, positive treatment experiences, and unmet rehabilitation needs. This group of EDS-HT/JHS patients has significant decrements in HRQoL and many unmet treatment needs, as well as a risk for iatrogenic injuries. We identify several approaches to help meet patients' needs and improve joint rehabilitation in patients with EDS-HT/JHS. (c) 2016 Wiley Periodicals, Inc. PMID- 27273747 TI - Toy Age-Labeling: An Overview for Pediatricians of How Toys Receive Their Age Safety and Developmental Designations. AB - Injuries related to toys continue to cause significant childhood morbidity and mortality, despite considerable government regulation of the toy industry. Recent controversy related to toys that contain strong magnets demonstrate the dangers they pose to children. The pediatric community is often unaware of how toys receive their developmental and safety labeling and the degree to which age labeling on toys can be discretionary. Toy labeling has 2 basic manifestations. The first, safety labeling for hazards like small parts, balloons, or small balls that may present a choking risk, is mandatory. The second, "developmental" age labeling, describes the age of the children for which the toy is intended, and sometimes has discretionary components. This article provides a review of the regulations governing toy age-safety standards and how they are reflected on toy packaging to help pediatric practitioners apply safety advice across settings and patient characteristics. We review the existing age-labeling regulations and processes and discuss the major areas where children remain vulnerable despite labeling. Finally, we list some recommendations for counseling parents about toy safety. PMID- 27273749 TI - Parent Health Literacy, Depression, and Risk for Pediatric Injury. AB - BACKGROUND: Population-wide research on the impact of parent health literacy to children's health outcomes is limited. We assessed the relationship of low parent health literacy to a range of pediatric health risks within a large cohort of primary care patients. METHODS: Data were from 17 845 English- and Spanish speaking parents of children aged <=7 years presenting for well-child care. We used a 3-item screener to measure health literacy. Outcomes included secondhand smoke exposure, asthma treatment nonadherence, parent depression, child-rearing practices, injury prevention, and parent first-aid knowledge. We summarized study variables with descriptive statistics and then performed multivariable logistic regression to identify associations between low parent literacy and our dependent measures. RESULTS: Mean child age was 4.8 years (SD 3.7); 36.5% of parent respondents had low health literacy. In models adjusted for child gender, race/ethnicity, insurance, age, and parent language preference, low parent health literacy was related to a range of pediatric health risks, including parent depression (adjusted odds ratio [AOR] 1.32; 95% confidence interval 1.18-1.48), firearm access (AOR 1.68; 1.49-1.89), not having a working smoke detector (AOR 3.54; 2.74-4.58), and lack of first-aid knowledge about choking (AOR 1.67; 1.44 1.93) and burns (AOR 1.45; 1.29-1.63). Children of parents with low health literacy were also more likely to watch >2 hours of television per day (AOR 1.27; 1.17-1.36). CONCLUSIONS: Low parent health literacy is independently and significantly related to parent depression, child television viewing, and at-risk family behaviors associated with child injury. Use of low-literacy approaches to health-behavior interventions may be essential to address common child morbidities. PMID- 27273748 TI - Bottle Size and Weight Gain in Formula-Fed Infants. AB - BACKGROUND: Formula-fed infants may be at greater risk for overfeeding and rapid weight gain. Different size bottles are used for feeding infants, although little is known about whether bottle size is related to weight gain in bottle-fed infants. METHODS: Data from the Greenlight Intervention Study, a cluster randomized trial to prevent childhood obesity at 4 pediatric resident clinics, were used to analyze the exposure to regular (<6 oz) or large (>=6 oz) bottle size at the 2-month visit on changes in weight, weight-for-age z score (WAZ), and weight-for-length z score (WLZ) at the 6-month visit. Using multivariable regression, we adjusted for potential confounders (birth weight, gender, age, weight measures at 2 months, parent race/ethnicity, education, household income and size, time between 2- and 6-month visits, and first child status). RESULTS: Forty-five percent (n = 386; 41% black, 35% Hispanic, 23% white, 2% other) of infants at the 2-month visit were exclusively formula-fed, and 44% used large (>=6 oz) bottles. Infants whose parents fed with large bottles had 0.21 kg (95% confidence interval [CI]: 0.05 to 0.37) more weight change, 0.24 U (95% CI: 0.07 to 0.41) more change in WAZ, and 0.31 U (95% CI: 0.08 to 0.54) more change in WLZ during this period than infants fed with regular bottles. CONCLUSIONS: Using a large bottle in early infancy independently contributed to greater weight gain and change in WLZ at the 6-month visit. Although growth in infancy is complex, bottle size may be a modifiable risk factor for rapid infant weight gain and later obesity among exclusively formula-fed infants. PMID- 27273750 TI - Sequencing and comparison of the Rickettsia genomes from the whitefly Bemisia tabaci Middle East Asia Minor I. AB - The whitefly, Bemisia tabaci, harbors the primary symbiont 'Candidatus Portiera aleyrodidarum' and a variety of secondary symbionts. Among these secondary symbionts, Rickettsia is the only one that can be detected both inside and outside the bacteriomes. Infection with Rickettsia has been reported to influence several aspects of the whitefly biology, such as fitness, sex ratio, virus transmission and resistance to pesticides. However, mechanisms underlying these differences remain unclear, largely due to the lack of genomic information of Rickettsia. In this study, we sequenced the genome of two Rickettsia strains isolated from the Middle East Asia Minor 1 (MEAM1) species of the B. tabaci complex in China and Israel. Both Rickettsia genomes were of high coding density and AT-rich, containing more than 1000 coding sequences, much larger than that of the coexisted primary symbiont, Portiera. Moreover, the two Rickettsia strains isolated from China and Israel shared most of the genes with 100% identity and only nine genes showed sequence differences. The phylogenetic analysis using orthologs shared in the genus, inferred the proximity of Rickettsia in MEAM1 and Rickettsia bellii. Functional analysis revealed that Rickettsia was unable to synthesize amino acids required for complementing the whitefly nutrition. Besides, a type IV secretion system and a number of virulence-related genes were detected in the Rickettsia genome. The presence of virulence-related genes might benefit the symbiotic life of the bacteria, and hint on potential effects of Rickettsia on whiteflies. The genome sequences of Rickettsia provided a basis for further understanding the function of Rickettsia in whiteflies. PMID- 27273751 TI - The influence of gender and age on the thickness and echo-density of skin. AB - BACKGROUND: The more recent use of ultrasound scanning allows a direct measurement on unmodified skin, and is considered to be a reliable method for in vivo measurement of epidermal and dermal thickness. The objective of this study was to assess the influence of gender and age on the thickness and echo-density of skin measured by high frequency ultrasonography (HFUS). MATERIALS AND METHODS: This study was carried out on 30 healthy volunteers (17 female, 13 male) with age range of 24-61 years old. The thickness and echo-density of dermis as well as epidermal entrance echo thickness in five anatomic sites (cheek, neck, palm, dorsal foot, and sole) were measured using two different types of B mode HFUS, 22 and 50 MHz frequencies. RESULTS: The epidermal entrance echo thickness and thickness of dermis in males were higher than females, which was statistically significant on neck and dorsum of foot. The echo-density of dermis was higher in females on all sites, but was only statistically significant on neck. The epidermal entrance echo thickness and thickness of dermis in young age group was statistically higher than old group on sole and dorsal of the foot respectively. Overall, the skin thickness decreased with age. CONCLUSION: High frequency ultrasonography method provides a simple non-invasive method for evaluating the skin thickness and echo-density. Gender and age have significant effect on these parameters. Differences in study method, population, and body site likely account for different results previously reported. PMID- 27273752 TI - Medial lower leg perforators: An anatomical study of their distribution and characteristics. AB - PURPOSE: The integument of the medial lower leg is underestimated as a donor site for local and distant reconstructions. Comprehensive knowledge of its perforator anatomy is lacking. This study aims to determine perforator location and characteristics and to compare these regarding the proximal, middle and distal third of the medial lower leg. MATERIALS AND METHODS: The medial lower leg region (MLLR) of 16 cadavers was delineated and investigated after injecting the popliteal artery with acrylic paint. Following dissection, all perforators larger than 0.3 mm were localized and mapped. Their course, source vessel, length and diameter were subsequently documented. RESULTS: Overall, 122 perforators were found, 102 (83.6%) originating from the posterior tibial artery, 16 (13.1%) from the medial sural artery and 4 (3.3%) from the anterior tibial artery. A mean of 7.6 +/- 2.4 perforators (range 4-13) per MLLR was found. Most perforators (42.6%) were localized in the distal third of the MLLR, followed by the middle (36.9%) and proximal third (20.5%). The largest and longest perforators were found in the proximal third of the MLLR (diameter 1.4 mm, length 9.1 cm), followed by the middle and distal third respectively. Of all musculocutaneous perforators, the majority (78.6%) was located in the middle third of the MLLR. Of all septocutaneous perforators, most (55.3%) were found in the distal third of the MLLR. A small number of unexpected anatomical variants were found. CONCLUSION: In each third of the MLLR different perforator characteristics were found. Knowledge of these characteristics can be used to direct the reconstructive plan. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:319-326, 2017. PMID- 27273753 TI - Is near-infrared light neuroprotective? PMID- 27273754 TI - Intravoxel incoherent motion diffusion-weighted imaging of the pancreas: Characterization of benign and malignant pancreatic pathologies. AB - PURPOSE: To evaluate the diagnostic value of apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) parameters in differentiating patients with either a normal pancreas (NP), pancreatic ductal adenocarcinoma (PDAC), neuroendocrine tumor (NET), solid pseudopapillary tumor (SPT), acute pancreatitis (AcP), vs. autoimmune pancreatitis (AIP). MATERIALS AND METHODS: In all, 84 pathologically confirmed pancreatic tumors (60 PDACs, 15 NETs, 9 SPTs), 20 pancreatitis (13 AcPs, 7 AIPs), and 30 NP subjects underwent IVIM diffusion weighted imaging using 10 b-values (0-900 sec/mm2 ) at 1.5T. The ADC, pure molecular diffusion coefficient (Dslow ), perfusion fraction (f), and perfusion related diffusion coefficient (Dfast ) were calculated and compared using a Kruskal-Wallis test and post-hoc Dunn procedure. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance. RESULTS: The f and Dfast of the PDAC were significantly lower than that of the NP (f = 0.10 vs. 0.24; Dfast = 42.21 vs. 71.74 * 10-3 mm2 /sec; P < 0.05). In ROC analysis, f showed the best diagnostic performance (area-under-the-curve, 0.919) among all parameters in differentiating PDAC from NP (P <= 0.001). The f values of AcP (0.11) and AIP (0.13) and the Dfast values of SPT (20.48 * 10-3 mm2 /sec) and AcP (24.49 * 10-3 mm2 /sec) were significantly lower compared with NP (f = 0.24; Dfast = 71.74 * 10-3 mm2 /sec; P < 0.05). For NET, the f (0.21) was significantly higher than that of PDAC (0.10, P < 0.01). CONCLUSION: Perfusion related parameters f and Dfast are more helpful in characterizing pancreatic diseases than ADC or Dslow . The PDCA, SPT, AcP, and AIP were characterized by reduced f and Dfast values compared with normal pancreas. The f value might help in differentiating between PDAC and NET. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:260-269. PMID- 27273755 TI - Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair. AB - Dental pulp stem cells (DPSC) are neural crest-derived ecto-mesenchymal stem cells that can relatively easily and non-invasively be isolated from the dental pulp of extracted postnatal and adult teeth. Accumulating evidence suggests that DPSC have great promise as a cellular therapy for central nervous system (CNS) and retinal injury and disease. The mode of action by which DPSC confer therapeutic benefit may comprise multiple pathways, in particular, paracrine mediated processes which involve a wide array of secreted trophic factors and is increasingly regarded as the principal predominant mechanism. In this concise review, we present the current evidence for the use of DPSC to repair CNS damage, including recent findings on retinal ganglion cell neuroprotection and regeneration in optic nerve injury and glaucoma. Stem Cells 2017;35:61-67. PMID- 27273756 TI - UDP-glycosyltransferase 72B1 catalyzes the glucose conjugation of monolignols and is essential for the normal cell wall lignification in Arabidopsis thaliana. AB - Glycosylation of monolignols has been found to be widespread in land plants since the 1970s. However, whether monolignol glycosylation is crucial for cell wall lignification and how it exerts effects are still unknown. Here, we report the identification of a mutant ugt72b1 showing aggravated and ectopic lignification in floral stems along with arrested growth and anthocyanin accumulation. Histochemical assays and thioacidolysis analysis confirmed the enhanced lignification and increased lignin biosynthesis in the ugt72b1 mutant. The loss of UDP-glycosyltransferase UGT72B1 function was responsible for the lignification phenotype, as demonstrated by complementation experiments. Enzyme activity analysis indicated that UGT72B1 could catalyze the glucose conjugation of monolignols, especially coniferyl alcohol and coniferyl aldehyde, which was confirmed by analyzing monolignol glucosides of UGT72B1 transgenic plants. Furthermore, the UGT72B1 gene was strongly expressed in young stem tissues, especially xylem tissues. However, UGT72B1 paralogs, such as UGT72B2 and UGT72B3, had weak enzyme activity toward monolignols and weak expression in stem tissues. Transcriptomic profiling showed that UGT72B1 knockout resulted in extensively increased transcript levels of genes involved in monolignol biosynthesis, lignin polymerization and cell wall-related transcription factors, which was confirmed by quantitative real-time PCR assays. These results provided evidence that monolignol glucosylation catalyzed by UGT72B1 was essential for normal cell wall lignification, thus offering insight into the molecular mechanism of cell wall development and cell wall lignification. PMID- 27273758 TI - Bacterial microbiomes from vertically transmitted fungal inocula of the leaf cutting ant Atta texana. AB - Microbiome surveys provide clues for the functional roles of symbiotic microbial communities and their hosts. In this study, we elucidated bacterial microbiomes associated with the vertically transmitted fungal inocula (pellets) used by foundress queens of the leaf-cutting ant Atta texana as starter-cultures for new gardens. As reference microbiomes, we also surveyed bacterial microbiomes of foundress queens, gardens and brood of incipient nests. Pseudomonas, Acinetobacter, Propionibacterium and Corynebacterium were consistently present in high abundance in microbiomes. Some pellet and ant samples contained abundant bacteria from an Entomoplasmatales-clade, and a separate PCR-based survey of Entomoplasmatales bacteria in eight attine ant-genera from Brazil placed these bacteria in a monophyletic clade within the bacterial genus Mesoplasma. The attine ant-Mesoplasma association parallels a similar association between a closely related, monophyletic Entomoplasmatales-clade and army ants. Of thirteen A. texana nests surveyed, three nests with exceptionally high Mesoplasma abundance died, whereas the other nests survived. It is unclear whether Mesoplasma was the primary cause of mortality, or Mesoplasma became abundant in moribund nests for non-pathogenic reasons. However, the consistent and geographically widespread presence of Mesoplasma suggests an important functional role in the association with attine ants. PMID- 27273757 TI - Dynamic ruffling distortion of the heme substrate in non-canonical heme oxygenase enzymes. AB - Recent work by several groups has established that MhuD, IsdG, and IsdI are non canonical heme oxygenases that induce significant out-of-plane ruffling distortions of their heme substrates enroute to mycobilin or staphylobilin formation. However, clear explanations for the observations of "nested" S = 1/2 VTVH MCD saturation magnetization curves at cryogenic temperatures, and exchange broadened (1)H NMR resonances at physiologically-relevant temperatures have remained elusive. Here, MCD and NMR data have been acquired for F23A and F23W MhuD-heme-CN, in addition to MCD data for IsdI-heme-CN, in order to complete assembly of a library of spectroscopic data for cyanide-inhibited ferric heme with a wide range of ruffling deformations. The spectroscopic data were used to evaluate a number of computational models for cyanide-inhibited ferric heme, which ultimately led to the development of an accurate NEVPT2/CASSCF model. The resulting model has a shallow, double-well potential along the porphyrin ruffling coordinate, which provides clear explanations for the unusual MCD and NMR data. The shallow, double-well potential also implies that MhuD-, IsdG-, and IsdI-bound heme is dynamic, and the functional implications of these dynamics are discussed. PMID- 27273759 TI - Reply to Cataldo (2016): Arrhythmia associated with buprenorphine and methadone reported to the Food and Drug Administration. PMID- 27273760 TI - Stewart-Bluefarb syndrome revisited. AB - Stewart-Bluefarb syndrome (SBS) is a subtype of pseudo-Kaposi sarcoma (PKS), which is associated with congenital arteriovenous malformation. It is a rare syndrome, characterized by cutaneous lesions with onset in the second decade of life. We report a case of SBS in a 33-year-old man presenting with a 15-year history of unilateral, reddish-brown, raised lesions on his right lower leg and the dorsum of his foot. Diagnosis of PKS was confirmed by histopathology and radiology. We report the clinical features, aetiopathogenesis, differential diagnosis and treatment of this rare condition. PMID- 27273761 TI - Scalable procedure for the fragmentation of hydroperoxides mediated by copper and iron tetrafluoroborate salts. AB - An improved protocol for the formal elimination of propene from organic substrates is reported. This process entails the ozonolytic conversion of an alkene to a methoxy hydroperoxide which undergoes fragmentation mediated by copper and iron. The use of soluble Cu(BF4)2 and Fe(BF4)2 results in reproducible results up to a 100 gram scale. PMID- 27273762 TI - Optimal hash arrangement of tentacles in jellyfish. AB - At first glance, the trailing tentacles of a jellyfish appear to be randomly arranged. However, close examination of medusae has revealed that the arrangement and developmental order of the tentacles obey a mathematical rule. Here, we show that medusa jellyfish adopt the best strategy to achieve the most uniform distribution of a variable number of tentacles. The observed order of tentacles is a real-world example of an optimal hashing algorithm known as Fibonacci hashing in computer science. PMID- 27273763 TI - Embedding Raman Tags between Au Nanostar@Nanoshell for Multiplex Immunosensing. AB - Novel Raman tags with various reporter molecules embedded in between gold nanostar (AuNS) and gold nanoshell are developed, showing significantly enhanced surface-enhanced Raman scattering intensity compared to gold nanoparticle-based composites. Immunoassay using these AuNS@tag@shell structures is highly specific with sensitivity down to 0.1 pg mL-1 , and is capable of multiplex detection, making them highly promising for biosensing applications. PMID- 27273764 TI - Ultrahigh Thermal Conductivity of Interface Materials by Silver-Functionalized Carbon Nanotube Phonon Conduits. AB - An ultrahigh thermal conductivity (kappa = 160 W m(-1) K(-1) ) of thermal interface materials is achieved with a high enhancement factor (96). A small amount (2.3 vol%) of 1D multiwalled carbon nanotubes (MWNTs) with high kappa constructs effective phonon transport pathways between microscale silver-flake islands, and a solid phonon transport junction is realized by the coalescence of silver nanoparticles pre-functionalized on the MWNTs. PMID- 27273765 TI - Experiment-Driven Modeling of Crystalline Phosphorus Nitride P3 N5 : Wide-Ranging Implications from a Unique Structure. AB - Nitridophosphates have emerged as advanced materials due to their structural variability and broad technical applicability. Their binary parent compound P3 N5 , a polymeric network of corner- and edge-sharing PN4 tetrahedra with N and N sites, is a particularly interesting example. We present a study of the band gap and electronic structure of alpha-P3 N5 by using soft X-ray spectroscopy measurements and DFT calculations. The band gap, which is crucial for all applications, is measured to be 5.87+/-0.20 eV. This agrees well with the calculated, indirect band gap of 5.21 eV. The density of states are found to show dramatic variation between the nonequivalent N sites and a high degree of covalency. Coupled to these results is what is, to our knowledge, the largest core hole shift reported to date for a soft X-ray absorption spectrum. We propose an intuitive bonding scheme for alpha-P3 N5 that explains the observed band gap and unique density of states, while providing a framework for predicting these properties in known and yet to be discovered PN compounds. We briefly consider the implications of these results for new low-dimensional P and PN materials, which alongside graphene, could become important materials for nanoelectronics. PMID- 27273766 TI - YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells. AB - Myelination is essential for nervous system function. Schwann cells interact with neurons and the basal lamina to myelinate axons using known receptors, signals and transcription factors. In contrast, the transcriptional control of axonal sorting and the role of mechanotransduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. We describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice, we show that Taz is required in Schwann cells for radial sorting and myelination and that Yap is redundant with Taz. Yap and Taz are activated in Schwann cells by mechanical stimuli and regulate Schwann cell proliferation and transcription of basal lamina receptor genes, both necessary for radial sorting of axons and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells. PMID- 27273767 TI - Topographical representation of odor hedonics in the olfactory bulb. AB - Hedonic value is a dominant aspect of olfactory perception. Using optogenetic manipulation in freely behaving mice paired with immediate early gene mapping, we demonstrate that hedonic information is represented along the antero-posterior axis of the ventral olfactory bulb. Using this representation, we show that the degree of attractiveness of odors can be bidirectionally modulated by local manipulation of the olfactory bulb's neural networks in freely behaving mice. PMID- 27273768 TI - Decoding subjective decisions from orbitofrontal cortex. AB - When making a subjective choice, the brain must compute a value for each option and compare those values to make a decision. The orbitofrontal cortex (OFC) is critically involved in this process, but the neural mechanisms remain obscure, in part due to limitations in our ability to measure and control the internal deliberations that can alter the dynamics of the decision process. Here we tracked these dynamics by recovering temporally precise neural states from multidimensional data in OFC. During individual choices, OFC alternated between states associated with the value of two available options, with dynamics that predicted whether a subject would decide quickly or vacillate between the two alternatives. Ensembles of value-encoding neurons contributed to these states, with individual neurons shifting activity patterns as the network evaluated each option. Thus, the mechanism of subjective decision-making involves the dynamic activation of OFC states associated with each choice alternative. PMID- 27273770 TI - Utilizing G2/M retention effect to enhance tumor accumulation of active targeting nanoparticles. AB - In recent years, active targeting strategies by ligand modification have emerged to enhance tumor accumulation of NP, but their clinical application was strictly restricted due to the complex preparation procedures, poor stability and serious toxicity. An effective and clinical translational strategy is required to satisfy the current problems. Interestingly, the internalization of NP is intimately related with cell cycle and the expression of receptors is not only related with cancer types but also cell cycle progression. So the cellular uptake of ligand modified NP may be related with cell cycle. However, few investigations were reported about the relationship between cell cycle and the internalization of ligand modified NP. Herein, cellular uptake of folic acid (FA) modified NP after utilizing chemotherapeutic to retain the tumor cells in G2/M phase was studied and a novel strategy was designed to enhance the active targeting effect. In our study, docetaxel (DTX) notably synchronized cells in G2/M phase and pretreatment with DTX highly improved in vitro and in vivo tumor cell targeting effect of FA decorated NP (FANP). Since FA was a most common used tumor active targeting ligand, we believe that this strategy possesses broader prospects in clinical application for its simplicity and effectiveness. PMID- 27273769 TI - SHANK3 controls maturation of social reward circuits in the VTA. AB - Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy. PMID- 27273771 TI - Angiotensin-converting enzyme insertion/deletion polymorphism is associated with cerebral white matter changes in Alzheimer's disease. AB - AIM: The presence of cerebral white matter changes (WMC) has been reported as an important predictor of the rapidity of cognitive decline in Alzheimer's disease (AD). The association between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and WMC in AD is yet to be elucidated. The present study aimed to examine the association between the ACE I/D polymorphism and WMC among AD patients in Taiwan. METHODS: A total of 403 patients clinically diagnosed with AD were recruited in a cross-sectional study carried out in an area hospital in Kaohsiung, Taiwan. The ACE I/D polymorphism was genotyped, and cerebral white matter rating was carried out using the visual rating scale for age-related white matter changes. RESULTS: The I allele was associated with a significantly lower total age-related white matter changes scale score compared with the D allele (4.83 vs 5.93, P = 0.013). The total age-related white matter changes scale score was significantly lower for the I/I genotype than for the I/D (4.37 vs 5.87, P = 0.009) and I/D + D/D genotypes (4.37 vs 5.91, P = 0.006), with no differences observed between the I/I + I/D and the D/D genotypes (5.08 vs 6.09, P = 0.373), after adjustment for age and hypertension. A stratified analysis by sex demonstrated that the I/I genotype was associated with significant lower WMC than other genotypes in women, but not in men. CONCLUSIONS: The present study supports the hypothesis that the ACE I/D polymorphism is associated with the severity of WMC in patients with AD. Patients with AD who are homozygous for the I allele might be less likely to develop WMC, especially women. Geriatr Gerontol Int 2017; 17: 945-950. PMID- 27273772 TI - Photo-induced morphological winding and unwinding motion of nanoscrolls composed of niobate nanosheets with a polyfluoroalkyl azobenzene derivative. AB - Photo-responsive nanoscrolls can be successfully fabricated by mixing a polyfluoroalkyl azobenzene derivative and a niobate nanosheet, which is exfoliated from potassium hexaniobate. In this study, we have found that the photo-responsive nanoscroll shows a morphological motion of winding and unwinding, which is basically due to the nanosheet sliding within the nanoscroll, by efficient photo-isomerization reactions of the intercalated azobenzene in addition to the interlayer distance change of the nanoscrolls. The relative nanosheet sliding of the nanoscroll is estimated to be ca. 280 nm from the AFM morphology analysis. The distance of the sliding motion is over 20 times that of the averaged nanosheet sliding in the azobenzene/niobate hybrid film reported previously. Photo-responsive nanoscrolls can be expected to be novel photo activated actuators and artificial muscle model materials. PMID- 27273784 TI - Quality of life improves in patients with chronic heart failure and Cheyne-Stokes respiration treated with adaptive servo-ventilation in a nurse-led heart failure clinic. AB - AIMS AND OBJECTIVES: The aim of this study was to investigate if quality of life improved in chronic heart failure patients with Cheyne-Stokes respiration treated with adaptive servo-ventilation in nurse-led heart failure clinic. BACKGROUND: Cheyne-Stokes respiration is associated with decreased quality of life in patients with chronic heart failure. Adaptive servo-ventilation is introduced to treat this sleep-disordered breathing. DESIGN: Randomised, controlled design. METHODS: Fifty-one patients (ranging from 53-84 years), New York Heart Association III-IV and/or left ventricular ejection fraction <=40% and Cheyne Stokes respiration were randomised to an intervention group who received adaptive servo-ventilation or a control group. Minnesota Living with Heart Failure Questionnaire was used to assess quality of life at randomisation and after three months. Both groups were followed in the nurse-led heart failure clinic. RESULT: Adaptive servo ventilation improved quality of life-scores both in a per protocol analysis and in an intention to treat analysis. Twenty-one patients dropped out of the study, nine in the control and 12 in the intervention group. CONCLUSION: Use of adaptive servo-ventilation improved quality of life in chronic heart failure patients with Cheyne-Stokes respiration. However, the drop-out rate was high. RELEVANCE TO CLINICAL PRACTICE: Chronic heart failure patients come regularly to the nurse-led heart failure clinic. The heart failure nurses' competency has to include knowledge of equipment to provide support and continuity of care to the patients. PMID- 27273785 TI - Vitamin D and pulmonary function in obese asthmatic children. AB - OBJECTIVE: Asthma-related morbidity is higher among children with vitamin D deficiency and obesity, morbidities that frequently co-exist among minority children. However, the effect of co-existent obesity and vitamin D deficiency on pulmonary function is poorly understood. METHODS: We compared percent-predicted values of pulmonary function across vitamin D categories among 72 obese and 71 normal-weight Hispanic and African-American children with asthma recruited at an urban children's hospital. Serum cytokines associated with Th1 and Th2 inflammation and 25-hydroxyvitamin D (25-OHD) were quantified in fasting serum. 25-OHD levels >=30 ng/ml were categorized as sufficient, <30 and >=20 ng/ml as insufficient, and <20 ng/ml as deficient. The role of inflammation was investigated by regression analysis. RESULTS: Vitamin D deficiency was present in 50% of children and did not differ by obese status. Forced Expiratory Volume in the first second (84.5 +/- 9.4 vs. 94.8 +/- 8.4, P < 0.001), and Functional Residual Capacity (67.5 +/- 20.1 vs. 79.3 +/- 19, P = 0.01) were lower among vitamin D deficient obese asthmatics than their sufficient counterparts, and Total Lung Capacity was lower than their insufficient counterparts (86.9 +/- 14.3 vs. 96.6 +/- 10, P = 0.01); similar associations were not observed in normal weight asthmatics and were not influenced by systemic inflammation. No association between Th1 and Th2 inflammatory measures, vitamin D deficiency, and pulmonary function tests was found. CONCLUSIONS: Vitamin D deficiency was associated with pulmonary function deficits among obese children, but not among normal-weight children with asthma, an association that was independent of Th1 and Th2 serum inflammatory measures. Vitamin D deficiency may be one potential mechanism underlying the obese-asthma phenotype. Pediatr Pulmonol. 2016;51:1276 1283. (c) 2016 Wiley Periodicals, Inc. PMID- 27273786 TI - Toxicity of long chain fatty acids towards acetate conversion by Methanosaeta concilii and Methanosarcina mazei. AB - Long-chain fatty acids (LCFA) can inhibit methane production by methanogenic archaea. The effect of oleate and palmitate on pure cultures of Methanosaeta concilii and Methanosarcina mazei was assessed by comparing methane production rates from acetate before and after LCFA addition. For both methanogens, a sharp decrease in methane production (> 50%) was observed at 0.5 mmol L(-1) oleate, and no methane was formed at concentrations higher than 2 mmol L(-1) oleate. Palmitate was less inhibitory than oleate, and M. concilii was more tolerant to palmitate than M. mazei, with 2 mmol L(-1) palmitate causing 11% and 64% methanogenic inhibition respectively. This study indicates that M. concilii and M. mazei tolerate LCFA concentrations similar to those previously described for hydrogenotrophic methanogens. In particular, the robustness of M. concilii might contribute to the observed prevalence of Methanosaeta species in anaerobic bioreactors used to treat LCFA-rich wastewater. PMID- 27273787 TI - Upregulation of human CYP2C9 expression by Bisphenol A via estrogen receptor alpha (ERalpha) and Med25. AB - Bisphenol A (BPA) is an important industrial chemical, mainly used in the manufacture of polycarbonate plastic and epoxy resins. Due to its widespread use, humans have a high risk of exposure to BPA. BPA has been found to have adverse health effects such as interfering with hormone-related pathways and is well known to act as an endocrine disruptor. The present study is the first to show the induction effect of BPA on gene expression and enzyme activity of CYP2C9, an important hepatic drug metabolizing enzyme in human. We further identify the mechanism of BPA upregulation of CYP2C9 expression. We show that BPA is able to transcriptionally activate CYP2C9 promoter through ERalpha and ERE site within the CYP2C9 promoter region in HepG2 cells, and can induce CYP2C9 gene expression and enzyme activity in human primary hepatocytes. Moreover, we demonstrate that Med25, a variable member of the Mediator complex, is a coactivator of ligand activated ERalpha that interacts with ERalpha through its C-terminal LXXLL motif after BPA exposure, and is functionally involved in BPA-induced transcriptional regulation of CYP2C9 expression and enzyme activity. Our findings suggest that BPA exposure has a potential risk for adverse health effects in human liver metabolism by upregulation of CYP2C9 expression. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 970-978, 2017. PMID- 27273789 TI - Reply. PMID- 27273788 TI - Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. AB - Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPalpha in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis. PMID- 27273791 TI - A-site compositional effects in Ga-doped hollandite materials of the form BaxCsyGa2x+yTi8-2x-yO16: implications for Cs immobilization in crystalline ceramic waste forms. AB - The hollandite structure is a promising crystalline host for Cs immobilization. A series of Ga-doped hollandite BaxCsyGa2x+yTi8-2x-yO16 (x = 0, 0.667, 1.04, 1.33; y = 1.33, 0.667, 0.24, 0) was synthesized through a solid oxide reaction method resulting in a tetragonal hollandite structure (space group I4/m). The lattice parameter associated with the tunnel dimension was found to increases as Cs substitution in the tunnel increased. A direct investigation of cation mobility in tunnels using electrochemical impedance spectroscopy was conducted to evaluate the ability of the hollandite structure to immobilize cations over a wide compositional range. Hollandite with the largest tunnel size and highest aspect ratio grain morphology resulting in rod-like microstructural features exhibited the highest ionic conductivity. The results indicate that grain size and optimized Cs stoichiometry control cation motion and by extension, the propensity for Cs release from hollandite. PMID- 27273792 TI - Intensive Treatment and Severe Hypoglycemia Among Adults With Type 2 Diabetes. AB - IMPORTANCE: Intensive glucose-lowering treatment among patients with non-insulin requiring type 2 diabetes may increase the risk of hypoglycemia. OBJECTIVES: To estimate the prevalence of intensive treatment and the association between intensive treatment, clinical complexity, and incidence of severe hypoglycemia among adults with type 2 diabetes who are not using insulin. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of administrative, pharmacy, and laboratory data from the OptumLabs Data Warehouse from January 1, 2001, through December 31, 2013. The study included nonpregnant adults 18 years or older with type 2 diabetes who achieved and maintained a hemoglobin A1c (HbA1c) level less than 7.0% without use of insulin and had no episodes of severe hypoglycemia or hyperglycemia in the prior 12 months. MAIN OUTCOMES AND MEASURES: Risk-adjusted probability of intensive treatment and incident severe hypoglycemia, stratified by patient clinical complexity. Intensive treatment was defined as use of more glucose-lowering medications than recommended by practice guidelines at specific index HbA1c levels. Severe hypoglycemia was ascertained by ambulatory, emergency department, and hospital claims for hypoglycemia during the 2 years after the index HbA1c test. Patients were categorized as having high vs low clinical complexity if they were 75 years or older, had dementia or end-stage renal disease, or had 3 or more serious chronic conditions. RESULTS: Of 31 542 eligible patients (median age, 58 years; interquartile range, 51-65 years; 15 483 women [49.1%]; 18 188 white [57.7%]), 3910 (12.4%) had clinical complexity. The risk adjusted probability of intensive treatment was 25.7% (95% CI, 25.1%-26.2%) in patients with low clinical complexity and 20.8% (95% CI, 19.4%-22.2%) in patients with high clinical complexity. In patients with low clinical complexity, the risk adjusted probability of severe hypoglycemia during the subsequent 2 years was 1.02% (95% CI, 0.87%-1.17%) with standard treatment and 1.30% (95% CI, 0.98% 1.62%) with intensive treatment (absolute difference, 0.28%; 95% CI, -0.10% to 0.66%). In patients with high clinical complexity, intensive treatment significantly increased the risk-adjusted probability of severe hypoglycemia from 1.74% (95% CI, 1.28%-2.20%) with standard treatment to 3.04% (95% CI, 1.91% 4.18%) with intensive treatment (absolute difference, 1.30%; 95% CI, 0.10% 2.50%). CONCLUSIONS AND RELEVANCE: More than 20% of patients with type 2 diabetes received intensive treatment that may be unnecessary. Among patients with high clinical complexity, intensive treatment nearly doubles the risk of severe hypoglycemia. PMID- 27273793 TI - The crystal structure of the major pneumococcal autolysin LytA in complex with a large peptidoglycan fragment reveals the pivotal role of glycans for lytic activity. AB - The pneumococcal autolysin LytA is a key virulence factor involved in several important functions including DNA competence, immune evasion and biofilm formation. Here, we present the 1.05 A crystal structure of the catalytic domain of LytA in complex with a synthetic cell-wall-based peptidoglycan (PG) ligand that occupies the entire Y-shaped substrate-binding crevice. As many as twenty one amino-acid residues are engaged in ligand interactions with a majority of these interactions directed towards the glycan strand. All saccharides are intimately bound through hydrogen bond, van der Waals and CH-pi interactions. Importantly, the structure of LytA is not altered upon ligand binding, whereas the bound ligand assumes a different conformation compared to the unbound NMR based solution structure of the same PG-fragment. Mutational study reveals that several non-catalytic glycan-interacting residues, structurally conserved in other amidases from Gram-positive Firmicutes, are pivotal for enzymatic activity. The three-dimensional structure of the LytA/PG complex provides a novel structural basis for ligand restriction by the pneumococcal autolysin, revealing for the first time an importance of the multivalent binding to PG saccharides. PMID- 27273790 TI - Therapeutic potential of NADPH oxidase 1/4 inhibitors. AB - : The NADPH oxidase (NOX) family of enzymes produces ROS as their sole function and is becoming recognized as key modulators of signal transduction pathways with a physiological role under acute stress and a pathological role after excessive activation under chronic stress. The seven isoforms differ in their regulation, tissue and subcellular localization and ROS products. The most studied are NOX1, 2 and 4. Genetic deletion of NOX1 and 4, in contrast to NOX2, has revealed no significant spontaneous pathologies and a pathogenic relevance of both NOX1 and 4 across multiple organs in a wide range of diseases and in particular inflammatory and fibrotic diseases. This has stimulated interest in NOX inhibitors for therapeutic application. GKT136901 and GKT137831 are two structurally related compounds demonstrating a preferential inhibition of NOX1 and 4 that have suitable properties for in vivo studies and have consequently been evaluated across a range of disease models and compared with gene deletion. In contrast to gene deletion, these inhibitors do not completely suppress ROS production, maintaining some basal level of ROS. Despite this and consistent with most gene deletion studies, these inhibitors are well tolerated and slow or prevent disease progression in a range of models of chronic inflammatory and fibrotic diseases by modulating common signal transduction pathways. Clinical trials in patients with GKT137831 have demonstrated excellent tolerability and reduction of various markers of chronic inflammation. NOX1/4 inhibition may provide a safe and effective therapeutic strategy for a range of inflammatory and fibrotic diseases. LINKED ARTICLES: This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. PMID- 27273794 TI - Successful Transplantation of Human Kidneys Deemed Untransplantable but Resuscitated by Ex Vivo Normothermic Machine Perfusion. AB - We report the successful transplantation of a pair of human kidneys that were declined for transplantation due to inadequate in situ perfusion but subsequently transplanted after perfusion and assessment using ex vivo normothermic perfusion (EVNP). The kidneys were from a 35-year-old man, a donation after circulatory death donor. Both kidneys were declined by all UK transplant centers. On arrival, the kidneys had significant areas of incomplete clearance of blood from the microcirculation that did not clear after a further attempt to flush them. Kidneys underwent 60 min of EVNP with an oxygenated packed red blood cell-based solution warmed to 35.2 degrees C. During EVNP, the patchy areas cleared in both kidneys. The mean renal blood flow and total urine output were 68.0 mL/min/100 g and 560 mL in the left kidney and 59.9 mL/min/100 g, 430 mL in the right, respectively. Based on the EVNP perfusion parameters, both kidneys were deemed suitable for transplantation. They were transplanted without any complications, and both recipients had initial graft function. The serum creatinine levels at 3 months were 1.2 mg/dl in the recipient of the left kidney and 1.62 mg/dl in the recipient of the right kidney. EVNP technology can be used to assess and rescue kidneys previously deemed unsuitable for transplantation. PMID- 27273795 TI - Better living with hyper-mutation. AB - The simplest forms of mutations, base substitutions, typically have negative consequences, aside from their existential role in evolution and fitness. Hypermutations, mutations on steroids, occurring at frequencies of 10(-2) -10(-4) per base pair, straddle a domain between fitness and death, depending on the presence or absence of regulatory constraints. Two facets of hypermutation, one in Escherichia coli involving DNA polymerase V (pol V), the other in humans, involving activation-induced deoxycytidine deaminase (AID) are portrayed. Pol V is induced as part of the DNA-damage-induced SOS regulon, and is responsible for generating the lion's share of mutations when catalyzing translesion DNA synthesis (TLS). Four regulatory mechanisms, temporal, internal, conformational, and spatial, activate pol V to copy damaged DNA and then deactivate it. On the flip side of the coin, SOS-induced pols V, IV, and II mutate undamaged DNA, thus providing genetic diversity heightening long-term survival and evolutionary fitness. Fitness in humans is principally the domain of a remarkably versatile immune system marked by somatic hypermutations (SHM) in immunoglobulin variable (IgV) regions that ensure antibody (Ab) diversity. AID initiates SHM by deaminating C -> U, favoring hot WRC (W = A/T, R = A/G) motifs. Since there are large numbers of trinucleotide motif targets throughout IgV, AID must exercise considerable catalytic restraint to avoid attacking such sites repeatedly, which would otherwise compromise diversity. Processive, random, and inefficient AID catalyzed dC deamination simulates salient features of SHM, yet generates B-cell lymphomas when working at the wrong time in the wrong place. Environ. Mol. Mutagen. 57:421-434, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273796 TI - Mechanical elongation of astrocyte processes to create living scaffolds for nervous system regeneration. AB - Following brain injury or neurodegenerative disease, successful regeneration requires orchestrated migration of neurons and reformation of long-distance communication fibres, or axons. Such extensive regeneration does not occur in the mature brain; however, during embryonic development, pathways formed by glial cells extend several millimeters (mm) to create 'living scaffolds' for targeted neural cell migration and axonal pathfinding. Techniques to recapitulate long process outgrowth in glial cells have proven elusive, preventing the exploitation of this developmental mechanism for regeneration. In the current study, astrocytes were induced to form a network of interconnected processes that were subjected to controlled mechanical tension in vitro using custom-built mechanobioreactors. We discovered a specific micron (MUm)-scale mechanical growth regime that induced elongation of the astrocytic processes to a remarkable length of 2.5 mm at an optimal rate of 12.5 MUm/h. More rapid mechanical regimes (> 20 MUm/h) caused greater incidence of process degeneration or outright breakage, whereas slow regimes (< 4 MUm/h) led to adaptive motility, thus failing to achieve process elongation. Cellular phenotype for this astrocytic 'stretch growth' was confirmed based on presentation of the intermediate filament glial fibrillary acidic protein (GFAP). Mechanical elongation resulted in the formation of dense bundles of aligned astrocytic processes. Importantly, seeded neurons readily adhered to, and extended neurites directly along, the elongated astrocytic processes, demonstrating permissiveness to support neuronal growth. This is the first demonstration of the controlled application of mechanical forces to create long astrocytic processes, which may form the backbone of tissue engineered 'living scaffolds' that structurally emulate radial glia to facilitate neuroregeneration. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273797 TI - Publication Rate and Evidence-Based Evaluation of Abstracts Presented at the American College of Veterinary Surgeon's Annual Meeting. AB - OBJECTIVE: To document the publication rate of abstracts presented at 10 ACVS conferences and report the time required for publication and level of evidence. STUDY DESIGN: Literature review. METHODS: All scientific abstracts published in the ACVS proceedings from 2001 to 2010 were reviewed. The level of evidence of each abstract was evaluated and scored (1-4). Publication information was determined after a broad bibliographic search through multiple online databases. RESULTS: The overall publication rate for ACVS abstracts (n=1,395) was 66% and 11% were published before conference presentation. The majority of abstracts focused on the dog (35%) or the horse (33%). Most (90%) abstracts were submitted to veterinary-based journals. The median time (interquartile range [IQR]) from abstract presentation to journal submission was 222 days (107-541), from journal submission to acceptance for publication was 122 days (89-185), and from acceptance to publication in a journal was 208 days (151-289). The time from abstract presentation to final publication took 449 days (238-794). Of the abstracts, 4% were of level 1 evidence, 9% level 2, 66% level 3, and 21% level 4. Studies with a higher level of evidence were submitted, accepted, and published quicker than ones with a lower level of evidence. The publication rate was 61%, 71%, 68%, and 65% for level 1, 2, 3, 4 evidence, respectively. CONCLUSION: The publication rate of scientific abstracts presented at the ACVS conferences is comparable to other biomedical conferences. The subject matter is limited in scope and focused mainly on dogs or horses. Most abstracts contained lower level of evidence. Studies with higher levels of evidence were submitted, accepted, and published more timely. However, the publication rate was similar for abstracts of all levels of evidence. PMID- 27273798 TI - Effects of corn straw or mixed forage diet on rumen fermentation parameters of lactating cows using a wireless data logger. AB - The objective of this study was to evaluate the effect of two different forage types on rumen fermentation parameters and profiles using a wireless data logger. Eight lactating cows were randomly assigned to one of two dietary treatments with a low forage diet with corn straw (CS) or a high forage diet with mixed forage (MF) as the forage source, respectively. Dietary physically effective neutral detergent fiber (peNDF) content was 11.3% greater in CS. Dry matter intake and milk fatty acid content decreased upon CS (P < 0.05). Ruminal pH, temperature and oxidation reduction potential (ORP) were monitored for 14 weeks. The CS group had significantly higher pH but lower temperature and ORP compared to MF (P < 0.01). With the CS diet regime, pH at the time before morning feeding, rumination and post-ingestion were significantly higher than those in the MF group (P < 0.05). However, times with the ruminal pH below 6.0 and 5.8 were significantly reduced (P < 0.05), whereas ruminal pH below 5.6 tended to be lower (P = 0.07). The results indicated that rumen fermentation parameters were affected by forage types and dietary peNDF content might be predominant in ruminal pH regulation. PMID- 27273799 TI - Oxidation State 10 Exists. AB - In a recent paper, Wang et al. found an iridium-containing compound with a formal oxidation state of 9. This is the highest oxidation state ever found in a stable compound. To learn if this is the highest chemical oxidation state possible, Kohn Sham density functional theory was used to study various compounds, including PdO4 (2+) , PtO4 (2+) , PtO3 F2 (2+) , PtO4 OH(+) , PtO5 , and PtO4 SH(+) , in which the metal has an oxidation state of 10. It was found that PtO4 (2+) has a metastable state that is kinetically stable with a barrier height for decomposition of 31 kcal mol(-1) and a calculated lifetime of 0.9 years. All other compounds studied would readily decompose to lower oxidation states. PMID- 27273800 TI - Keratoacanthoma formation after skin grafting: A brief report and pathophysiological hypothesis. AB - Keratoacanthoma formation after skin grafting is rare. We report the third case in the literature of multiple keratoacanthomas developed at both split-thickness skin graft donor and recipient sites. We provide possible explanations for this poorly understood phenomenon and highlight its implications on treatment options. PMID- 27273801 TI - Persistence With Conventional Triple Therapy Versus a Tumor Necrosis Factor Inhibitor and Methotrexate in US Veterans With Rheumatoid Arthritis. AB - OBJECTIVE: To compare persistence and adherence to triple therapy with the nonbiologic disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), hydroxychloroquine, and sulfasalazine, versus a tumor necrosis factor inhibitor (TNFi) plus MTX in patients with rheumatoid arthritis (RA). METHODS: Administrative and laboratory data were analyzed for US Veterans with RA initiating triple therapy or TNFi + MTX between January 2006 and December 2012. Treatment persistence 365 days postindex was calculated using 3 definitions. Definition 1 required no gap in therapy of >=90 days for any drug in the original combination. Definition 2 required no added or switched DMARD, no decrease to nonbiologic DMARD monotherapy, and no termination of all DMARD therapies. Definition 3 was similar to definition 2 but allowed a switch to another drug within the same class. Adherence used a proportion of days covered of >=80%. Propensity-weighted analysis with matched weights was used to balance covariates. RESULTS: The analysis included 4,364 RA patients (TNFi + MTX, n = 3,204; triple therapy, n = 1,160). In propensity-weighted analysis, patients in the TNFi + MTX group were significantly more likely than patients in the triple therapy group to satisfy all persistence criteria in definition 1 (risk difference [RD] 13.1% [95% confidence interval (95% CI) 9.2-17.0]), definition 2 (RD 6.4% [95% CI 2.3 10.5]), and definition 3 (RD 9.5% [95% CI 5.5-13.6]). Patients in the TNFi + MTX group also exhibited higher adherence during the first year (RD 7.2% [95% CI 3.8 10.5]). CONCLUSION: US Veterans with RA were significantly more likely to be persistent and adherent to combination therapy with TNFi + MTX than triple therapy with nonbiologic DMARDs. PMID- 27273802 TI - Comparing the validity of informant and self-reports of personality using laboratory indices of emotional responding as criterion variables. AB - Personality traits relate to risk for psychopathology and can inform predictions about treatment outcome. In an effort to obtain a comprehensive index of personality, informant reports of personality are sometimes obtained in addition to self-reports of personality. However, there is limited research comparing the validity of self- and informant reports of personality, particularly among those with internalizing psychopathology. This is important given that informants may provide an additional (and perhaps different) perspective on individuals' personality. The present study therefore compared how both reports of positive affectivity (PA) and negative affectivity (NA) relate to psychophysiological and subjective measures of emotional responding to positive and negative stimuli. Given that our sample (n = 117) included individuals with no history of psychopathology, as well as individuals with major depressive disorder (MDD) and/or panic disorder (PD), we were also able to explore whether these internalizing diagnoses moderated the association between personality reports and measures of emotional responding. Informant-reported PA predicted physiological responses to positive stimuli (but not negative). Informant-reported NA predicted physiological responses to negative stimuli (but not positive). Self-reported personality did not predict physiological responding, but did predict subjectively measured emotional responding (NA for negative responding, PA for positive responding). Diagnoses of internalizing psychopathology (PD or MDD) did not moderate these associations. Results suggest self- and informant reports of personality may each provide valid indices of an individual's emotional response tendencies, but predict different aspects of those tendencies. PMID- 27273803 TI - Etiologies of uterine malformations. AB - Ranging from aplastic uterus (including Mayer-Rokitansky-Kuster-Hauser syndrome) to incomplete septate uterus, uterine malformations as a group are relatively frequent in the general population. Specific causes remain largely unknown. Although most occurrences ostensibly seem sporadic, familial recurrences have been observed, which strongly implicate genetic factors. Through the study of animal models, human syndromes, and structural chromosomal variation, several candidate genes have been proposed and subsequently tested with targeted methods in series of individuals with isolated, non-isolated, or syndromic uterine malformations. To date, a few genes have garnered strong evidence of causality, mainly in syndromic presentations (HNF1B, WNT4, WNT7A, HOXA13). Sequencing of candidate genes in series of individuals with isolated uterine abnormalities has been able to suggest an association for several genes, but confirmation of a strong causative effect is still lacking for the majority of them. We review the current state of knowledge about the developmental origins of uterine malformations, with a focus on the genetic variants that have been implicated or associated with these conditions in humans, and we discuss potential reasons for the high rate of negative results. The evidence for various environmental and epigenetic factors is also reviewed. (c) 2016 Wiley Periodicals, Inc. PMID- 27273804 TI - Fever treatment with a catheter-based heat exchange system in the neurointensive care unit. PMID- 27273805 TI - Cell death and inflammation: the case for IL-1 family cytokines as the canonical DAMPs of the immune system. AB - It is well known that necrotic cells are capable of promoting inflammation through releasing so-called endogenous 'danger signals' that can promote activation of macrophages, dendritic cells, and other sentinel cells of the innate immune system. However, the identity of these endogenous proinflammatory molecules, also called damage-associated molecular patterns (DAMPs), has been debated since the 'danger model' was first advanced 20 years ago. While a relatively large number of molecules have been proposed to act as DAMPs, little consensus has emerged concerning which of these represent the key activators of sterile inflammation. Here I argue that the canonical DAMPs have long been hiding in plain sight, in the form of members of the extended IL-1 cytokine family (IL 1alpha, IL-1beta, IL-18, IL-33, IL-36alpha, IL-36beta, and IL-36gamma). The latter cytokines possess all of the characteristics expected of endogenous DAMPs and initiate inflammation in a manner strikingly similar to that utilized by the other major category of inflammatory triggers, pathogen-associated molecular patterns (PAMPs). Furthermore, many PAMPs upregulate the expression of IL-1 family DAMPs, enabling robust synergy between these distinct classes of inflammatory triggers. Thus, multiple lines of evidence now suggest that IL-1 family cytokines represent the key initiators of necrosis-initiated sterile inflammation, as well as amplifiers of inflammation in response to infection associated tissue injury. PMID- 27273806 TI - Characterising the variations in ethnic skin colours: a new calibrated data base for human skin. AB - BACKGROUND: Accurate skin colour measurements are important for numerous medical applications including the diagnosis and treatment of cutaneous disorders and the provision of maxillofacial soft tissue prostheses. METHODS: In this study, we obtained accurate skin colour measurements from four different ethnic groups (Caucasian, Chinese, Kurdish, Thai) and at four different body locations (Forehead, cheek, inner arm, back of hand) with a view of establishing a new skin colour database for medical and cosmetic applications. Skin colours are measured using a spectrophotometer and converted to a device-independent standard colour appearance space (CIELAB) where skin colour is expressed as values along the three dimensions: Lightness L*, Redness a* and Yellowness b*. Skin colour differences and variation are then evaluated as a function of ethnicity and body location. RESULTS: We report three main results: (1) When plotted in a standard colour appearance space (CIELAB), skin colour distributions for the four ethnic groups overlap significantly, although there are systematic mean differences. Between ethnicities, the most significant skin colour differences occur along the yellowness dimension, with Thai skin exhibiting the highest yellowness (b*) value and Caucasian skin the lowest value. Facial redness (a*) is invariant across the four ethnic groups. (2) Between different body locations, there are significant variations in redness (a*), with the forehead showing the highest redness value and the inner arm the lowest. (3) The colour gamut is smallest in the Chinese sample and largest in the Caucasian sample, with the Chinese gamut lying entirely the Caucasian gamut. Similarly, the largest variability in skin tones is found in the Caucasian group, and the smallest in the Chinese group. CONCLUSION: Broadly speaking, skin colour variation can be explained by two main factors: individual differences in lightness and yellowness are mostly due to ethnicity, whereas differences in redness are primarily due to different body locations. Variations in lightness are more idiosyncratic probably reflecting the large influence of environmental factors such as exposure to sun. PMID- 27273807 TI - The effect of lung deformation on the spatial distribution of pulmonary blood flow. AB - KEY POINTS: Pulmonary perfusion measurement using magnetic resonance imaging combined with deformable image registration enabled us to quantify the change in the spatial distribution of pulmonary perfusion at different lung volumes. The current study elucidated the effects of tidal volume lung inflation [functional residual capacity (FRC) + 500 ml and FRC + 1 litre] on the change in pulmonary perfusion distribution. Changes in hydrostatic pressure distribution as well as transmural pressure distribution due to the change in lung height with tidal volume inflation are probably bigger contributors to the redistribution of pulmonary perfusion than the changes in pulmonary vasculature resistance caused by lung tissue stretch. ABSTRACT: Tidal volume lung inflation results in structural changes in the pulmonary circulation, potentially affecting pulmonary perfusion. We hypothesized that perfusion is recruited to regions receiving the greatest deformation from a tidal breath, thus ensuring ventilation-perfusion matching. Density-normalized perfusion (DNP) magnetic resonance imaging data were obtained in healthy subjects (n = 7) in the right lung at functional residual capacity (FRC), FRC+500 ml, and FRC+1.0 l. Using deformable image registration, the displacement of a sagittal lung slice acquired at FRC to the larger volumes was calculated. Registered DNP images were normalized by the mean to estimate perfusion redistribution (nDNP). Data were evaluated across gravitational regions (dependent, middle, non-dependent) and by lobes (upper, RUL; middle, RML; lower, RLL). Lung inflation did not alter mean DNP within the slice (P = 0.10). The greatest expansion was seen in the dependent region (P < 0.0001: dependent vs non dependent, P < 0.0001: dependent vs middle) and RLL (P = 0.0015: RLL vs RUL, P < 0.0001: RLL vs RML). Neither nDNP recruitment to RLL [+500 ml = -0.047(0.145), +1 litre = 0.018(0.096)] nor to dependent lung [+500 ml = -0.058(0.126), +1 litre = 0.023(0.106)] were found. Instead, redistribution was seen in decreased nDNP in the non-dependent [+500 ml = -0.075(0.152), +1 litre = -0.137(0.167)) and increased nDNP in the gravitational middle lung [+500 ml = 0.098(0.058), +1 litre = 0.093(0.081)] (P = 0.01). However, there was no significant lobar redistribution (P < 0.89). Contrary to our hypothesis, based on the comparison between gravitational and lobar perfusion data, perfusion was not redistributed to the regions of the most inflation. This suggests that either changes in hydrostatic pressure or transmural pressure distribution in the gravitational direction are implicated in the redistribution of perfusion away from the non dependent lung. PMID- 27273808 TI - Versatility of pedicled anterolateral thigh flap in gynecologic reconstruction after vulvar cancer extirpative surgery. AB - OBJECTIVE: Ablative surgery for vulvar cancer can involve the resection of perineum, vagina, urethra, groins, mons pubis, and abdominal wall creating complex defects. In our opinion, ALT flap is an ideal flap for reconstruction, because of low incidence of complications, long pedicle outside the radiotherapy field, capability of carrying fascia and muscle, possibility of sensate reconstruction, and low donor site morbidity. The purpose of this report is to describe our experience with ALT flap for reconstruction after vulvar cancer extirpative surgery, discussing our indications for complex defects and focusing on its versatility. PATIENTS AND METHODS: We performed a retrospective review of 15 cases of complex postoncologic gynecological wounds, reconstructed with 16 pedicled ALT flap, after vulvar cancer ablative surgery between 2014 and 2016. Age of the patients ranged from 44 to 77, with mean age of 62.6. Postoperative outcomes were evaluated. RESULTS: The flap size ranged from 12 * 8 cm to 22 * 15 cm., in two cases we harvested vastus lateralis to fill the dead space after pelvic exenteration. In nine flaps, we could include only 1 perforator, in 7 we could use two, 5 were septocutaneous and 18 myocutaneous with a pedicle length ranging from9cm.to15cm.We had no flap necrosis.3 flaps showed dehiscence of a part of the wound that healed by dressings. In one case of obese patient the donor site showed partial wound edge necrosis, and required secondary grafting. During follow-up that ranged from 1 month to 2 years, cancer relapsed locally in 5 patients. Global performance and specific pain improved after surgery. CONCLUSION: ALT flap should be included in the first line options for reconstructions of complex defects resulting from vulvar cancer surgery because of its reliability and versatility. (c) 2016 Wiley Periodicals, Inc. Microsurgery 37:516-524, 2017. PMID- 27273810 TI - A second patient with a De Novo GABRB1 mutation and epileptic encephalopathy. PMID- 27273809 TI - Preparing a prescription drug monitoring program data set for research purposes. AB - PURPOSE: To develop a complete and consistent prescription drug monitoring program (PDMP) data set for use by drug safety researchers in evaluating patterns of high-risk use and potential abuse of scheduled drugs. METHODS: Using publically available data references from the US Food and Drug Administration and the Centers for Disease Control and Prevention, we developed a strategic methodology to assign drug categories based on pharmaceutical class for the majority of prescriptions in the PDMP data set. We augmented data elements required to calculate morphine milligram equivalents and assigned duration of action (short-acting or long acting) properties for a majority of opioids in the data set. RESULTS: About 10% of prescriptions in the PDMP data set did not have a vendor-assigned drug category, and 20% of opioid prescriptions were missing data needed to calculate risk metrics. Using inclusive methods, 19 133 167 (>99.9%) of prescriptions in the PDMP data set were assigned a drug category. For the opioid category, augmenting data elements resulted in 10 760 669 (99.8%) having required values to calculate morphine milligram equivalents and evaluate duration of action properties. CONCLUSIONS: Drug safety researchers who require a complete and consistent PDMP data set can use the methods described here to ensure that prescriptions of interest are assigned consistent drug categories and complete opioid risk variable values. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27273811 TI - Obsessional and Eating Disorder-related Intrusive Thoughts: Differences and Similarities Within and Between Individuals Vulnerable to OCD or to EDs. AB - Unwanted intrusive cognitions constitute the normal variant of clinically significant intrusive cognitions found in disorders such as obsessive-compulsive disorder (OCD) and eating disorders (EDs). This study investigates whether individuals who are vulnerable to OCD or EDs experience more intrusions than people with no vulnerability to these disorders, and it examines the consequences of obsessional (OITs) and eating disorder (EDITs) intrusions in the same individuals, taking into account their susceptibility to OCD, EDs or neither of the two. From a sample of 922 participants, three groups were formed: risk of OCD (n = 92), risk of EDs (n = 41) and a no-risk group (n = 100). EDITs were more frequent than OITs in the two risk groups. Within-group comparisons showed that in the OCD-risk group, the OIT had more negative consequences (interference, emotional distress, dysfunctional appraisals and neutralizing strategies) than the EDIT, whereas in the ED-risk group, the OIT and the EDIT instigated similar negative consequences. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 27273812 TI - Fetoscopic repair of spina bifida: safer and better? PMID- 27273813 TI - Maintaining weight loss after bariatric surgery: when the spectator role is no longer enough. AB - Bariatric (weight loss) surgery is the gold standard treatment for severe obesity. Concern exists that patients are regaining weight in the longer term. Success and cost-effectiveness of surgery are threatened due to the re-emergence of related conditions such as diabetes. This exploratory qualitative study investigates patients' expectations and experiences of weight regain (WR) 2 years or more after Roux-en-Y gastric bypass (RYGB). Ten participants (two men and eight women) who experienced WR were interviewed between 2 and 6 years following surgery. Findings highlight that participants reacted to initial weight loss as passive spectators and were unprepared for subsequent WR. Their tolerability of WR reduced as the amount of regain increased, suggesting a 'line of tolerance' for WR. WR was influenced by a new vulnerability arising from weight loss over time, and participants struggled to manage their own weight actively as surgical effects waned. They considered self-management skills, and carer and professional support to be limited at the time when WR was most likely to occur. Degrees of tolerability are noted in individuals regaining weight after RYGB. More studies are needed to further understand these problems. Pre- and post-operative support and teaching patients self-management skills may be helpful to minimize WR. PMID- 27273814 TI - Tampering of opioid analgesics: a serious challenge for public health? PMID- 27273816 TI - Rh(iii)-catalyzed C-H activation/cyclization of oximes with alkenes for regioselective synthesis of isoquinolines. AB - A Rh(iii)-catalyzed C-H activation/cyclization of oximes and alkenes for facile and regioselective access to isoquinolines has been developed. This protocol features mild reaction conditions and easily accessible starting materials, and has been applied to the concise synthesis of moxaverine. A kinetic isotope effect study was conducted and a plausible mechanism was proposed. PMID- 27273815 TI - High-fat diet-induced hypertension and autonomic imbalance are associated with an upregulation of CART in the dorsomedial hypothalamus of mice. AB - We evaluated herein whether diet-induced obesity alters sympathovagal balance, blood pressure, and neuropeptides levels at the hypothalamus and brainstem of mice. Male C57BL6J mice fed with a high-fat (HFD) or a high-fat high-sucrose (HFHSu), or a regular chow diet (C) for 8 weeks were evaluated for metabolic parameters and blood pressure, the latter being performed in conscious freely moving mice. Spectral analysis from the records of systolic blood pressure (SBP) and cardiac pulse intervals (PI) was performed to analyse the autonomic balance in the cardiovascular system. HFD-fed mice developed two distinct hemodynamic phenotypes: hypertensive mice (HFD-H) with high systolic and diastolic BP levels and hypertension-resistant mice (HFD-R) whose BP levels were similar to C group. Spectral analysis of SBP and PI variabilities indicate that the low-frequency (LF)/high-frequency (HF) ratio, which is an index of sympathovagal balance, is higher in HFD-H compared to HFD-R. Along with hypertension and higher LF/HF ratio, HFD-H mice presented increased hypothalamic mRNA levels of cocaine- and amphetamine-regulated transcript (CART), and increased CART-positive neurones in the dorsomedial hypothalamus (DMH) by high-fat diet when compared to C group. Despite developing obesity to similar levels than HFD feeding, intake of a HFHSu was not associated with hypertension in mice neither CART levels increase. Collectively, our main findings indicate that high-fat diet induced-hypertension and autonomic imbalance are associated to an upregulation of CART levels in the DMH of mice. PMID- 27273817 TI - Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation-A Computational Study. AB - Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort. PMID- 27273818 TI - Integration of Artificial Photosynthesis System for Enhanced Electronic Energy Transfer Efficacy: A Case Study for Solar-Energy Driven Bioconversion of Carbon Dioxide to Methanol. AB - Biocatalyzed artificial photosynthesis systems provide a promising strategy to store solar energy in a great variety of chemicals. However, the lack of direct interface between the light-capturing components and the oxidoreductase generally hinders the trafficking of the chemicals and photo-excited electrons into the active center of the redox biocatalysts. To address this problem, a completely integrated artificial photosynthesis system for enhanced electronic energy transfer efficacy is reported by combining co-axial electrospinning/electrospray and layer-by-layer (LbL) self-assembly. The biocatalysis part including multiple oxidoreductases and coenzymes NAD(H) was in situ encapsulated inside the lumen polyelectrolyte-doped hollow nanofibers or microcapsules fabricated via co-axial electrospinning/electrospray; while the precise and spatial arrangement of the photocatalysis part, including electron mediator and photosensitizer for photo regeneration of the coenzyme, was achieved by ion-exchange interaction-driven LbL self-assembly. The feasibility and advantages of this integrated artificial photosynthesis system is fully demonstrated by the catalyzed cascade reduction of CO2 to methanol by three dehydrogenases (formate, formaldehyde, and alcohol dehydrogenases), incorporating the photo-regeneration of NADH under visible-light irradiation. Compared to solution-based systems, the methanol yield increases from 35.6% to 90.6% using the integrated artificial photosynthesis. This work provides a novel platform for the efficient and sustained production of a broad range of chemicals and fuels from sunlight. PMID- 27273819 TI - Intramolecular Tetrylene Lewis Adducts: Synthesis and Reactivity. AB - A series of benzyl(diphenylphosphino) and o-phenyl(diphenlyphosphino) substituted germylenes and plumbylenes were synthesized by nucleophilic substitution between the respective lithium reagent and tetrylene halide. The Lewis pairs were characterized by X-ray crystallography and NMR spectroscopy. The reactivity of the tetrylenes was investigated with respect to azide addition. In the germylene case, the germaniumimide was formed as the kinetically controlled product, which rearranges upon heating to give the phosphinimide. The stannylene and plumbylene derivatives react with adamantylazide to give the azide adducts. 1-Pentene reacts diastereoselectively with the phosphagermirane to give a cyclic addition product. Trimethysilylacetylene shows an addition with the benzylphosphino-substituted germylene and plumbylene to give the cycloheteropentene molecules. The addition product between phenylacetylene and the four membered Ge-P adduct shows after addition at room temperature a 1,4-phenylmigration to give a cyclic phosphine. Alkylnitrene insertion into a Ge-C bond of the alkyne addition product of the phosphagermirane was found in reaction with adamantylazide. PMID- 27273820 TI - Cognitive impairment is independently associated with definitive and possible sarcopenia in hospitalized older adults: The prevalence and impact of comorbidities. AB - AIM: Older adults often present with several comorbidities, including sarcopenia. However, the prevalence of sarcopenia and its associations with other comorbidities in hospitalized older adults are unknown. The present study aimed to determine the prevalence of sarcopenia, and its associations with other comorbidities in hospitalized older adults. METHODS: The present cross-sectional study included 619 patients admitted to a geriatric hospital. The prevalence of comorbidities in the presence and absence of sarcopenia, nutritional status (according to body mass index and the Mini-Nutritional Assessment-Short Form), and activities of daily living (according to the Barthel Index) were assessed. Sarcopenia was defined as skeletal muscle loss evaluated by both bioelectrical impedance and handgrip strength analyses. RESULTS: Of the 619 participants (mean age 83.0 +/- 8.2 years), 417 (67.4%) and 87 (14.1%) had definitive and possible sarcopenia, respectively. The prevalence rates of cognitive impairment and stroke were significantly higher in patients with definitive sarcopenia and those with possible sarcopenia than in those without sarcopenia (cognitive impairment 54.4%, 70.1% and 20.9%, respectively, P < 0.001; stroke 31.2%, 48.3% and 19.1%, respectively, P < 0.001). Multivariate logistic regression analysis showed that cognitive impairment was independently associated with sarcopenia after adjusting for age, sex, the Mini-Nutritional Assessment-Short Form score, Barthel Index and primary disease (adjusted odds ratio 1.98, 95% confidence interval 1.06-3.71; P = 0.032). CONCLUSIONS: Sarcopenia might be highly prevalent among hospitalized older adults. Furthermore, cognitive impairment might be an independent explanatory variable of sarcopenia. Therefore, further studies on sarcopenia in patients with cognitive impairment are warranted. Geriatr Gerontol Int 2017; 17: 1048-1056. PMID- 27273821 TI - Spirometer guided chest imaging in children: It is worth the effort! AB - PURPOSE: Computed tomography (CT) and magnetic resonance imaging (MRI) scans are used to assess and monitor several pediatric lung diseases. It is well recognized that lung volume at the moment of acquisition has a major impact on the appearance of lung parenchyma and airways. Importantly, the sensitivity of chest CT and MRI to detect bronchiectasis and gas trapping is highly dependent on adequate volume control during the image acquisition. This paper describes a feasible method to obtain accurate control of lung volume during chest imaging in pediatric patients with lung disease. PROCEDURE: A procedure to obtain maximal respiratory manoeuvres with spirometry guidance during image acquisition for CT and MRI is described. This procedure requires training of the subject, an MRI compatible spirometer and close collaboration between a lung function scientist and the radiographer. A good to excellent target volume level for the inspiratory or expiratory scan can be achieved in around 90% of children. An important condition for this success rate is the training of the subject, executed prior to each chest CT or MRI, and instructions by the lung function scientist during the chest CT. CONCLUSION: Implementing lung volume guidance with a spirometer is an important and feasible step to standardize chest imaging and to optimize the diagnostic yield of chest CT and MRI in children with lung disease. Training and the collaborative effort by a lung function scientist and radiographer is the key factor for success of this procedure. Pediatr Pulmonol. 2017;52:48-56. (c) 2016 Wiley Periodicals, Inc. PMID- 27273823 TI - Immunohistochemical distinction of metastases of renal cell carcinoma with molecular analysis of overexpression of the chemokines CXCR2 and CXCR3 as independent positive prognostic factors for the tumorigenesis. AB - Renal cell carcinoma (RCC) represents, on average, over 90% of all malignancies of the kidney that occur in adults in both sexes. Chemokine receptors expression has been found in many kinds of cancer and at tumor metastasis site. We determined CXCR2 and CXCR3 expression in RCC by immunohistochemistry method and analyzed the prognostic value of these markers. Our finding demonstrated that CXCR3 were highly overexpressed in renal cancer tissues compared with those adjacent normal kidney tissues (P < 0.001). The results showed that high expression of CXCR3 was markedly correlated with metastasis (P = 0.021) and tumor stage (P = 0.031). CXCR2 were overexpressed in renal cancer tissues compared with those adjacent normal kidney tissues (P < 0.001). Our result showed that CXCR2 expression was correlated with high grade (P = 0.024), advanced stage (P = 0.029) and metastasis (P = 0.018). The log-rank test revealed that high CXCR2 and CXCR3 expressions are related to poorer overall survival (P < 0.001; P < 0.001). In conclusion, this study indicates the correlation of CXCR3 and CXCR3 with progression of RCC. In addition, high CXCR3 andCXCR2 expressions were correlated with shorter overall survival. (c) 2016 IUBMB Life, 68(8):629-633, 2016. PMID- 27273824 TI - How Can Vaccines Contribute to Solving the Antimicrobial Resistance Problem? AB - There is a growing appreciation for the role of vaccines in confronting the problem of antimicrobial resistance (AMR). Vaccines can reduce the prevalence of resistance by reducing the need for antimicrobial use and can reduce its impact by reducing the total number of cases. By reducing the number of pathogens that may be responsible for a particular clinical syndrome, vaccines can permit the use of narrower-spectrum antibiotics for empirical therapy. These effects may be amplified by herd immunity, extending protection to unvaccinated persons in the population. Because much selection for resistance is due to selection on bystander members of the normal flora, vaccination can reduce pressure for resistance even in pathogens not included in the vaccine. Some vaccines have had disproportionate effects on drug-resistant lineages within the target species, a benefit that could be more deliberately exploited in vaccine design. We describe the effects of current vaccines in controlling AMR, survey some vaccines in development with the potential to do so further, and discuss strategies to amplify these benefits. We conclude with a discussion of research and policy priorities to more fully enlist vaccines in the battle against AMR. PMID- 27273822 TI - Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species. AB - Fungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus, may lead to a variety of allergic reactions and life-threatening systemic infections in humans. Invasive aspergillosis occurs primarily in patients with severe immunodeficiency, and has dramatically increased in recent years. There are several factors at play that contribute to aspergillosis, including both fungus and host-related factors such as strain virulence and host pulmonary structure/immune status, respectively. The environmental tenacity of Aspergilllus, its dominance in diverse microbial communities/habitats, and its ability to navigate the ecophysiological and biophysical challenges of host infection are attributable, in large part, to a robust stress-tolerance biology and exceptional capacity to generate cell-available energy. Aspects of its stress metabolism, ecology, interactions with diverse animal hosts, clinical presentations and treatment regimens have been well-studied over the past years. Here, we synthesize these findings in relation to the way in which some Aspergillus species have become successful opportunistic pathogens of human- and other animal hosts. We focus on the biophysical capabilities of Aspergillus pathogens, key aspects of their ecophysiology and the flexibility to undergo a sexual cycle or form cryptic species. Additionally, recent advances in diagnosis of the disease are discussed as well as implications in relation to questions that have yet to be resolved. PMID- 27273826 TI - History Leaves Its Mark on Soil Bacterial Diversity. AB - Dispersal is closely tied to the origin and maintenance of microbial diversity. With its focus on a narrow group of soil bacteria, recent work by Andam and colleagues on Streptomyces has provided perhaps the strongest support so far that some bacterial diversity in soils can be attributed to regional endemism (C. P. Andam et al., mBio 7:e02200-15, 2016, http://dx.doi.org/10.1128/mBio.02200-15). This means that dispersal is limited enough to allow for evolutionary diversification. Further analyses suggest that signatures of climate conditions more than 10,000 years ago can be detected in contemporary populations of this genus. These legacies have implications for how future climate change might alter soil microbial diversity. PMID- 27273825 TI - Plasmodium falciparum Histidine-Rich Protein II Compromises Brain Endothelial Barriers and May Promote Cerebral Malaria Pathogenesis. AB - Cerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum It is characterized by parasite sequestration, inflammatory cytokine production, and vascular leakage. A distinguishing feature of P. falciparum infection is parasite production and secretion of histidine-rich protein II (HRPII). Plasma HRPII is a diagnostic and prognostic marker for falciparum malaria. We demonstrate that disruption of a human cerebral microvascular endothelial barrier by P. falciparum-infected erythrocytes depends on expression of HRPII. Purified recombinant or native HRPII can recapitulate these effects. HRPII action occurs via activation of the inflammasome, resulting in decreased integrity of tight junctions and increased endothelial permeability. We propose that HRPII is a virulence factor that may contribute to cerebral malaria by compromising endothelial barrier integrity within the central nervous system. IMPORTANCE: Cerebral malaria is a devastating disease. Patients have high levels of the protein HRPII in their blood. We have found that endothelial cell barriers become leaky when treated with concentrations of HRPII similar to those found in patients. This result suggests that HRPII may be important in cerebral malaria. Our finding that HRPII functions by causing inflammation suggests points of intervention for therapy or vaccination against this disease. PMID- 27273827 TI - The Prevalence of Inappropriate Image Duplication in Biomedical Research Publications. AB - Inaccurate data in scientific papers can result from honest error or intentional falsification. This study attempted to determine the percentage of published papers that contain inappropriate image duplication, a specific type of inaccurate data. The images from a total of 20,621 papers published in 40 scientific journals from 1995 to 2014 were visually screened. Overall, 3.8% of published papers contained problematic figures, with at least half exhibiting features suggestive of deliberate manipulation. The prevalence of papers with problematic images has risen markedly during the past decade. Additional papers written by authors of papers with problematic images had an increased likelihood of containing problematic images as well. As this analysis focused only on one type of data, it is likely that the actual prevalence of inaccurate data in the published literature is higher. The marked variation in the frequency of problematic images among journals suggests that journal practices, such as prepublication image screening, influence the quality of the scientific literature. PMID- 27273828 TI - Exocytosis of Alphaherpesvirus Virions, Light Particles, and Glycoproteins Uses Constitutive Secretory Mechanisms. AB - Many molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy assay of pseudorabies virus (PRV) exocytosis, based on total internal reflection fluorescence (TIRF) microscopy and a virus-encoded pH-sensitive fluorescent probe. Here, we use this assay to distinguish three classes of viral exocytosis in a nonpolarized cell type: (i) trafficking of viral glycoproteins to the plasma membrane, (ii) exocytosis of viral light particles, and (iii) exocytosis of virions. We find that viral glycoproteins traffic to the cell surface in association with constitutive secretory Rab GTPases and exhibit free diffusion into the plasma membrane after exocytosis. Similarly, both virions and light particles use these same constitutive secretory mechanisms for egress from infected cells. Furthermore, we show that viral light particles are distinct from cellular exosomes. Together, these observations shed light on viral glycoprotein trafficking steps that precede virus particle assembly and reinforce the idea that virions and light particles share a biogenesis and trafficking pathway. IMPORTANCE: The alphaherpesviruses, including the important human pathogens herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), are among the few viruses that have evolved to exploit the mammalian nervous system. These viruses typically cause mild recurrent herpetic or zosteriform lesions but can also cause debilitating herpes encephalitis, more frequently in very young, old, immunocompromised, or nonnatural hosts. Importantly, many of the molecular and cellular mechanisms of viral assembly and egress remain unclear. This study addresses the trafficking of viral glycoproteins to the plasma membrane, exocytosis of light particles, and exocytosis of virions. Trafficking of glycoproteins affects immune evasion and pathogenesis and may precede virus particle assembly. The release of light particles may also contribute to immune evasion and pathogenesis. Finally, exocytosis of virions is important to understand, as this final step in the virus replication cycle produces infectious extracellular particles capable of spreading to the next round of host cells. PMID- 27273830 TI - PBX3 is a putative biomarker of aggressive prostate cancer. AB - There is a great need to identify new and better prognostic and predictive biomarkers to stratify prostate cancer patients for optimal treatment. The aims of this study were to characterize the expression profile of pre-B cell leukemia homeobox (PBX) transcription factors in prostate cancer with an emphasis on investigating whether PBX3 harbours any prognostic value. The expression profile of PBX3 and PBX1 in prostate tissue was determined by immunohistochemical and immunoblot analysis. Furthermore, the expression of PBX3 transcript variants was analyzed by RT-PCR, NanoString Technologies(r), and by analyzing RNA sequence data. The potential of PBX3 to predict prognosis, either at mRNA or protein level, was studied in four independent cohorts. PBX3 was mainly expressed in the nucleus of normal prostate basal cells, while it showed cytosolic expression in prostatic intraepithelial neoplasia and cancer cells. We detected four PBX3 transcript variants in prostate tissue. Competing risk regression analysis revealed that high PBX3 expression was associated with slower progression to castration resistant prostate cancer (sub-hazard ratio (SHR) 0.18, 95% CI: 0.081 0.42, p values < 0.001). PBX3 expression had a high predictive accuracy (area under the curve (AUC) = 0.82) when combined with Gleason score and age. Patients undergoing radical prostatectomy, with high levels of PBX3 mRNA, had improved prostate cancer specific survival compared to patients expressing low levels (SHR 0.21, 95% CI: 0.46-0.93, p values < 0.001, and AUC = 0.75). Our findings strongly indicate that PBX3 has potential as a biomarker, both as part of a larger gene panel and as an immunohistochemical marker, for aggressive prostate cancer. PMID- 27273831 TI - The Effect of Perfusate Volume on Amikacin Concentration in the Metacarpophalangeal Joint Following Cephalic Regional Limb Perfusion in Standing Horses. AB - OBJECTIVE: To determine the influence of 3 perfusate volumes on amikacin concentration in the metacarpophalangeal joint following cephalic regional limb perfusion (RLP) in standing horses. ANIMALS: Seven healthy horses. METHODS: Three perfusate volumes (100, 60, and 30 mL), containing 2 grams of amikacin, were tested during intravenous RLP at the cephalic vein, placing the tourniquet at mid antebrachium, in standing sedated horses. Synovial fluid was collected from the metacarpophalangeal joint before perfusion and at 30 and 120 minutes after perfusion. Serum samples were taken from the jugular vein at the same time points. Samples were analyzed for amikacin concentrations and a repeated measures ANOVA, followed by least squares difference pairwise comparisons to identify differences in amikacin concentration across perfusate volumes. Differences were considered significant at P<.05. RESULTS: The mean amikacin concentration in synovial fluid at 30 minutes after perfusion was significantly higher following perfusate volume of 100 mL (579 MUg/mL), compared to volumes of 60 mL (227 MUg/mL) or 30 mL (282 MUg/mL) (P<.05). When a threshold of 160 MUg/mL was used, more horses reached the synovial therapeutic threshold following perfusate volume of 100 mL (100%), than horses receiving 60 mL (43%) and 30 mL (57%) at 30 minutes after injection. CONCLUSION: The use of 100 mL volume for RLP at the cephalic vein in standing horses resulted in higher concentration of amikacin in the synovial fluid and is recommended for use in clinical cases. PMID- 27273829 TI - Bacterial Adrenergic Sensors Regulate Virulence of Enteric Pathogens in the Gut. AB - Enteric pathogens such as enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium, which is largely used as a surrogate EHEC model for murine infections, are exposed to several host neurotransmitters in the gut. An important chemical exchange within the gut involves the neurotransmitters epinephrine and/or norepinephrine, extensively reported to increase virulence gene expression in EHEC, acting through two bacterial adrenergic sensors: QseC and QseE. However, EHEC is unable to establish itself and cause its hallmark lesions, attaching and effacing (AE) lesions, on murine enterocytes. To address the role of these neurotransmitters during enteric infection, we employed C. rodentium Both EHEC and C. rodentium harbor the locus of enterocyte effacement (LEE) that is necessary for AE lesion formation. Here we show that expression of the LEE, as well as that of other virulence genes in C. rodentium, is also activated by epinephrine and/or norepinephrine. Both QseC and QseE are required for LEE gene activation in C. rodentium, and the qseC and qseE mutants are attenuated for murine infection. C. rodentium has a decreased ability to colonize dopamine beta-hydroxylase knockout (Dbh(-/-)) mice, which do not produce epinephrine and norepinephrine. Both adrenergic sensors are required for C. rodentium to sense these neurotransmitters and activate the LEE genes during infection. These data indicate that epinephrine and norepinephrine are sensed by bacterial adrenergic receptors during enteric infection to promote activation of their virulence repertoire. This is the first report of the role of these neurotransmitters during mammalian gastrointestinal (GI) infection by a noninvasive pathogen. IMPORTANCE: The epinephrine and norepinephrine neurotransmitters play important roles in gut physiology and motility. Of note, epinephrine and norepinephrine play a central role in stress responses in mammals, and stress has profound effects on GI function. Bacterial enteric pathogens exploit these neurotransmitters as signals to coordinate the regulation of their virulence genes. The bacterial QseC and QseE adrenergic sensors are at the center of this regulatory cascade. C. rodentium is a noninvasive murine pathogen with a colonization mechanism similar to that of EHEC, enabling the investigation of host signals in mice. The presence of these neurotransmitters in the gut is necessary for C. rodentium to fully activate its virulence program, in a QseC/QseE-dependent manner, to successfully colonize its murine host. Our study data provide the first example of epinephrine and norepinephrine signaling within the gut to stimulate infection by a bacterial pathogen in a natural animal infection. PMID- 27273832 TI - Overexpression of SepJ alters septal morphology and heterocyst pattern regulated by diffusible signals in Anabaena. AB - Filamentous, N2 -fixing, heterocyst-forming cyanobacteria grow as chains of cells that are connected by septal junctions. In the model organism Anabaena sp. strain PCC 7120, the septal protein SepJ is required for filament integrity, normal intercellular molecular exchange, heterocyst differentiation, and diazotrophic growth. An Anabaena strain overexpressing SepJ made wider septa between vegetative cells than the wild type, which correlated with a more spread location of SepJ in the septa as observed with a SepJ-GFP fusion, and contained an increased number of nanopores, the septal peptidoglycan perforations that likely accommodate septal junctions. The septa between heterocysts and vegetative cells, which are narrow in wild-type Anabaena, were notably enlarged in the SepJ overexpressing mutant. Intercellular molecular exchange tested with fluorescent tracers was increased for the SepJ-overexpressing strain specifically in the case of calcein transfer between vegetative cells and heterocysts. These results support an association between calcein transfer, SepJ-related septal junctions, and septal peptidoglycan nanopores. Under nitrogen deprivation, the SepJ overexpressing strain produced an increased number of contiguous heterocysts but a decreased percentage of total heterocysts. These effects were lost or altered in patS and hetN mutant backgrounds, supporting a role of SepJ in the intercellular transfer of regulatory signals for heterocyst differentiation. PMID- 27273833 TI - Structural Manipulation of Ruthenium(II) Polypyridine Nitrone Complexes to Generate Phosphorogenic Bioorthogonal Reagents for Selective Cellular Labeling. AB - We report a new class of ruthenium(II) polypyridine complexes functionalized with a nitrone group as phosphorogenic bioorthogonal probes. These complexes were very weakly emissive owing to rapid C=N isomerization of the nitrone moiety, but exhibited significant emission enhancement upon strain-promoted alkyne-nitrone cycloaddition (SPANC) reaction with bicyclo[6.1.0]nonyne (BCN)-modified substrates. The modification of nitrone with a dicationic ruthenium(II) polypyridine unit at the alpha-C-position and a phenyl ring at the N-position led to remarkably accelerated reaction kinetics, which are substantially greater (up to ~278 fold) than those of other acyclic nitrone-BCN systems. Interestingly, the complexes achieved specific cell membrane/cytosol staining upon specific labeling of an exogenous substrate, BCN-modified decane (BCN-C10), in live cells. Importantly, the in situ generation of the more lipophilic isoxazoline adduct in the cytoplasm resulted in increased cytotoxicity, highlighting a novel approach to apply the SPANC labeling technique in drug activation. PMID- 27273834 TI - Oxytocin receptor dynamics in the brain across development and species. AB - Oxytocin (OXT) signaling through the OXT receptor plays a significant role in a variety of physiological processes throughout the lifespan. OXT's effects depend on the tissue distribution of the receptor. This tissue specificity is dynamic and changes across development, and also varies with sex, experience, and species. The purpose of this review is to highlight these themes with examples from several life stages and several species. Important knowledge gaps will also be emphasized. Understanding the effective sites of action for OXT via its receptor will help refine hypotheses about the roles of this important neuropeptide in the experience-dependent development and expression of species typical social behavior. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 143-157, 2017. PMID- 27273835 TI - Estimation of sweat rates during cycling exercise by means of the closed chamber condenser technology. AB - BACKGROUND/AIM: Knowledge of local sweating patterns is of importance in occupational and exercise physiology settings. The recently developed closed chamber condenser technology (Biox Aquaflux(r) ) allows the measurement of evaporative skin water loss with a greater measurement capacity (up to 1325 g/h/m2 ) compared to traditional evaporimeters. The aim of this study was to evaluate the applicability of the Biox Aquaflux(r) to estimate sweat production during exercise. METHODS: Fourteen healthy subjects performed a 20-min cycle ergometer trial at respectively 55% heart rate (HRreserve and 75% HRreserve . Sweat production was estimated by measuring body weight before and after exercise, by calculating the amount of sweat collected in a patch, and by measuring the water flux (in g/h/m2 ) with the Biox Aquaflux(r) instrument. RESULTS: The Biox Aquaflux(r) instrument allowed the follow up of sweat kinetics at both intensities. Correlations between the measurement methods were all significant for the 75% HRreserve trial (with r ranging from 0.68 to 0.76) whilst for the 55% HRreserve a significant relation was detected between the patch method and the Biox Aquaflux(r) only (with r ranging from 0.41 to 0.79). CONCLUSION: The Biox Aquaflux(r) instrument is a practical and direct method for the estimation of local sweat rates under field conditions. PMID- 27273837 TI - Chronic intestinal pseudo-obstruction in a child harboring a founder Hirschsprung RET mutation. AB - Chronic intestinal pseudo obstruction (CIPO) is a rare clinical entity characterized by symptoms and signs of intestinal obstruction without either recognizable anatomical abnormalities or intestinal aganglionosis. A Chinese female infant presented to our institution with a clinical diagnosis of CIPO. Aganglionosis was ruled out by full thickness colonic and ileal biopsies and by rectal suction biopsies. Unexpectedly, direct sequencing and PCR amplification of RET proto-oncogene from peripheral blood extracted DNA identified a RET R114H mutation. This mutation has already been reported as strongly associated with Asian patients affected by Hirschsprung's disease (HSCR) and is considered a founder mutation in Asia. The same mutation has never been reported in patients with CIPO, so far. These findings support the role of RET in the development of the enteric nervous system but underline the importance of other genetic or environmental factors contributing to the gastrointestinal phenotype of the disease. Somehow, this RET R114H mutation proved to have a role in the etiology of both CIPO and HSCR and could contribute to a more diffuse imbalance of gut dysmotility. (c) 2016 Wiley Periodicals, Inc. PMID- 27273836 TI - Noninvasive Imaging of CCR2+ Cells in Ischemia-Reperfusion Injury After Lung Transplantation. AB - Ischemia-reperfusion injury-mediated primary graft dysfunction substantially hampers short- and long-term outcomes after lung transplantation. This condition continues to be diagnosed based on oxygen exchange parameters as well as radiological appearance, and therapeutic strategies are mostly supportive in nature. Identifying patients who may benefit from targeted therapy would therefore be highly desirable. Here, we show that C-C chemokine receptor type 2 (CCR2) expression in murine lung transplant recipients promotes monocyte infiltration into pulmonary grafts and mediates graft dysfunction. We have developed new positron emission tomography imaging agents using a CCR2 binding peptide, ECLi1, that can be used to monitor inflammatory responses after organ transplantation. Both 64 Cu-radiolabeled ECL1i peptide radiotracer (64 Cu-DOTA ECL1i) and ECL1i-conjugated gold nanoclusters doped with 64 Cu (64 CuAuNCs-ECL1i) showed specific detection of CCR2, which is upregulated during ischemia reperfusion injury after lung transplantation. Due to its fast pharmacokinetics, 64 Cu-DOTA-ECL1i functioned efficiently for rapid and serial imaging of CCR2. The multivalent 64 CuAuNCs-ECL1i with extended pharmacokinetics is favored for long term CCR2 detection and potential targeted theranostics. This imaging may be applicable for diagnostic and therapeutic purposes for many immune-mediated diseases. PMID- 27273838 TI - Febuxostat for Patients With Gout and Severe Chronic Kidney Disease: Which Is the Appropriate Dosage? Comment on the Article by Saag et al. PMID- 27273841 TI - Editorial: Translating the advances of biosensors from bench to bedside. AB - Biosensors have been found with numerous applications in many areas including genetic analysis, detection of infectious diseases, environmental monitoring and forensic analysis. We have witnessed rapid advances in this field, especially with the emergence of nanotechnology in the past decade. PMID- 27273839 TI - Effect of Pictorial Cigarette Pack Warnings on Changes in Smoking Behavior: A Randomized Clinical Trial. AB - IMPORTANCE: Pictorial warnings on cigarette packs draw attention and increase quit intentions, but their effect on smoking behavior remains uncertain. OBJECTIVE: To assess the effect of adding pictorial warnings to the front and back of cigarette packs. DESIGN, SETTING, AND PARTICIPANTS: This 4-week between participant randomized clinical trial was carried out in California and North Carolina. We recruited a convenience sample of adult cigarette smokers from the general population beginning September 2014 through August 2015. Of 2149 smokers who enrolled, 88% completed the trial. No participants withdrew owing to adverse events. INTERVENTIONS: We randomly assigned participants to receive on their cigarette packs for 4 weeks either text-only warnings (one of the Surgeon General's warnings currently in use in the United States on the side of the cigarette packs) or pictorial warnings (one of the Family Smoking Prevention and Tobacco Control Act's required text warnings and pictures that showed harms of smoking on the top half of the front and back of the cigarette packs). MAIN OUTCOMES AND MEASURES: The primary trial outcome was attempting to quit smoking during the study. We hypothesized that smokers randomized to receive pictorial warnings would be more likely to report a quit attempt during the study than smokers randomized to receive a text-only Surgeon General's warning. RESULTS: Of the 2149 participants who began the trial (1039 men, 1060 women, and 34 transgender people; mean [SD] age, 39.7 [13.4] years for text-only warning, 39.8 [13.7] for pictorial warnings), 1901 completed it. In intent-to-treat analyses (n = 2149), smokers whose packs had pictorial warnings were more likely than those whose packs had text-only warnings to attempt to quit smoking during the 4-week trial (40% vs 34%; odds ratio [OR], 1.29; 95% CI, 1.09-1.54). The findings did not differ across any demographic groups. Having quit smoking for at least the 7 days prior to the end of the trial was more common among smokers who received pictorial than those who received text-only warnings (5.7% vs 3.8%; OR, 1.53; 95% CI, 1.02-2.29). Pictorial warnings also increased forgoing a cigarette, intentions to quit smoking, negative emotional reactions, thinking about the harms of smoking, and conversations about quitting. CONCLUSIONS AND RELEVANCE: Pictorial warnings effectively increased intentions to quit, forgoing cigarettes, quit attempts, and successfully quitting smoking over 4 weeks. Our trial findings suggest that implementing pictorial warnings on cigarette packs in the United States would discourage smoking. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02247908. PMID- 27273842 TI - ACB2015: Biotechnology and bioeconomy for sustainable future. PMID- 27273844 TI - Effect of Nutrient Availability on Progenitor Cells in Zebrafish (Danio Rerio). AB - In zebrafish brains, populations of continuously proliferating cells are present during an entire life span. Under normal conditions, stem cells give rise to rapidly proliferating progenitors that quickly exit the cell cycle and differentiate. Hence fish are favorable models to study what regulates postembryonic neurogenesis. The aim of this study was to determine if optic tectum (OT) cell proliferation is halted during nutritional deprivation (ND) and whether or not it can be restored with refeeding. We examined the effect of ND on the proliferation of Neuroepithelial/Ependymal Progenitor cell (NeEPC) and transitory-amplifying progenitors (TAPs). Following ND, no PCNA immunostaining was found in OT of starved fish, while positive cell populations of PCNA positive progenitors are found at its periphery in control fish. This indicated that active proliferation stopped. To label retaining progenitor cells, BrdU was applied and a chase-period was accompanied by ND. Positive NeEPCs were detected in the external tectum marginal zone of starved fish suggesting that these progenitors are relatively immune to ND. Moreover in the internal tectum marginal zone labeled retaining cells were observed leaving the possibility that some arrested TAPs were present to readily restart proliferation when nutrition was returned. Our results suggest that neurogenesis was maintained during ND and that a normal proliferative situation was recovered after refeeding. We point to the mTOR pathway as a necessary pathway in progenitors to regulate their mitosis activity. Thus, this study highlights mechanisms involved in neural stem and progenitor cell homeostatic maintenance in an adverse situation. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 26-38, 2017. PMID- 27273843 TI - 'PrEP is not ready for our community, and our community is not ready for PrEP': pre-exposure prophylaxis for HIV for people who inject drugs and limits to the HIV prevention response. AB - BACKGROUND AND AIMS: Pre-exposure prophylaxis for HIV, or 'PrEP', is the use of antiretroviral medicines by people who are HIV-negative to protect themselves against acquiring HIV. PrEP has shown efficacy for preventing HIV acquisition. Despite the potential, many concerns have been voiced by people who inject drugs (PWID) and their organizations. There is a need to engage with these views and ensure their integration in to policy and strategy. This paper presents PWID views on PrEP to foster the uptake of these opinions into scientific and policy debate around PrEP METHODS: Critical analysis of a report of a community consultation led by the International Network of People who Use Drugs (INPUD). RESULTS: The INPUD report highlights enthusiasm from PWID for PrEP, but also three main concerns: the feasibility and ethics of PrEP, its potential use as a substitute for other harm reduction strategies and how a focus on PrEP heralds a re-medicalization of HIV. Each concern relates to evidenced gaps in essential services or opposition to harm reduction and PWID human rights. CONCLUSIONS: People who use drugs have fundamental concerns about the potential impacts of pre exposure prophylaxis for HIV which reflect a 'fault line' in HIV prevention: a predominance of biomedical approaches over community perspectives. Greater community engagement in HIV prevention strategy is needed, or we risk continuing to ignore the need for action on the underlying structural drivers and social context of the HIV epidemic. PMID- 27273845 TI - Estimated or Measured GFR in Living Kidney Donors Work-up? AB - The value of estimated glomerular filtration rate (eGFR) in living kidney donors screening is unclear. A recently published web-based application derived from large cohorts, but not living donors, calculates the probability of a measured GFR (mGFR) lower than a determined threshold. Our objectives were to validate the clinical utility of this tool in a cohort of living donors and to test two other strategies based on chronic kidney disease epidemiology collaboration (CKD-EPI) and on MDRD-eGFR. GFR was measured using 51 Cr- ethylene-diamine tetraacetic acid urinary clearance in 311 potential living kidney donors (178 women, mean age 50 +/- 11.6 years). The web-based tool was used to predict those with mGFR < 80 mL/min/1.73 m2 . Inputs to the application were sex, age, ethnicity, and plasma creatinine. In our cohort, a web-based probability of mGFR <90 mL/min/1.73 m2 higher than 2% had 100% sensitivity for detection of actual mGFR <80 mL/min/1.73 m2 . The positive predictive value was 0.19. A CKD-EPI-eGFR threshold of 104 mL/min/1.73 m2 and an MDRD-eGFR threshold of 100 mL/min/1.73 m2 had 100% sensitivity to detect donors with actual mGFR <80 mL/min/1.73 m2 . We obtained similar results in an external cohort of 354 living donors. We confirm the usefulness of the web-based application to identify potential donors who should benefit from GFR measurement. PMID- 27273846 TI - Urorectal septum malformation sequence-Fetal series with the description of a new "intermediate" variant. Time to refine the terminology? PMID- 27273847 TI - Model biases in rice phenology under warmer climates. AB - Climate-induced crop yields model projections are constrained by the accuracy of the phenology simulation in crop models. Here, we use phenology observations from 775 trials with 19 rice cultivars in 5 Asian countries to compare the performance of four rice phenology models (growing-degree-day (GDD), exponential, beta and bilinear models) when applied to warmer climates. For a given cultivar, the difference in growing season temperature (GST) varied between 2.2 and 8.2 degrees C in different trials, which allowed us to calibrate the models for lower GST and validate under higher GST, with three calibration experiments. The results show that in warmer climates the bilinear and beta phenology models resulted in gradually increasing bias for phenology predication and double yield bias per percent increase in phenology simulation bias, while the GDD and exponential models maintained a comparatively constant bias. The phenology biases were primarily attributed to varying phenological patterns to temperature in models, rather than on the size of the calibration dataset. Additionally, results suggest that model simulations based on multiple cultivars provide better predictability than using one cultivar. Therefore, to accurately capture climate change impacts on rice phenology, we recommend simulations based on multiple cultivars using the GDD and exponential phenology models. PMID- 27273848 TI - Molecular determinants of prokaryotic voltage-gated sodium channels for recognition of local anesthetics. AB - Local anesthetics (LAs) inhibit mammalian voltage-gated Na(+) channels (Navs) and are thus clinically important. LAs also inhibit prokaryotic Navs (BacNavs), which have a simpler structure than mammalian Navs. To elucidate the detailed mechanisms of LA inhibition to BacNavs, we used NavBh, a BacNav from Bacillus halodurans, to analyze the interactions of several LAs and quaternary ammoniums (QAs). Based on the chemical similarity of QA with the tertiary-alkylamine (TAA) group of LAs, QAs were used to determine the residues required for the recognition of TAA by NavBh. We confirmed that two residues, Thr220 and Phe227, are important for LA binding; a methyl group of Thr220 is important for recognizing both QAs and LAs, whereas Phe227 is involved in holding blockers at the binding site. In addition, we found that NavBh holds blockers in a closed state, consistent with the large inner cavity observed in the crystal structures of BacNavs. These findings reveal the inhibition mechanism of LAs in NavBh, where the methyl group of Thr220 provides the main receptor site for the TAA group and the bulky phenyl group of Phe227 holds the blockers inside the large inner cavity. These two residues correspond to the two LA recognition residues in mammalian Navs, which suggests the relevance of the LA recognition between BacNavs and mammalian Navs. PMID- 27273849 TI - Brief Report: Late-Onset Cryopyrin-Associated Periodic Syndrome Due to Myeloid Restricted Somatic NLRP3 Mosaicism. AB - OBJECTIVE: Gain-of-function NLRP3 mutations cause cryopyrin-associated periodic syndrome (CAPS), with gene mosaicism playing a relevant role in the pathogenesis. This study was undertaken to characterize the genetic cause underlying late-onset but otherwise typical CAPS. METHODS: We studied a 64-year-old patient who presented with recurrent episodes of urticaria-like rash, fever, conjunctivitis, and oligoarthritis at age 56 years. DNA was extracted from both unfractionated blood and isolated leukocyte and CD34+ subpopulations. Genetic studies were performed using both the Sanger method of DNA sequencing and next-generation sequencing (NGS) methods. In vitro and ex vivo analyses were performed to determine the consequences that the presence of the variant have in the normal structure or function of the protein of the detected variant. RESULTS: NGS analyses revealed the novel p.Gln636Glu NLRP3 variant in unfractionated blood, with an allele frequency (18.4%) compatible with gene mosaicism. Sanger sequence chromatograms revealed a small peak corresponding to the variant allele. Amplicon based deep sequencing revealed somatic NLRP3 mosaicism restricted to myeloid cells (31.8% in monocytes, 24.6% in neutrophils, and 11.2% in circulating CD34+ common myeloid progenitor cells) and its complete absence in lymphoid cells. Functional analyses confirmed the gain-of-function behavior of the gene variant and hyperactivity of the NLRP3 inflammasome in the patient. Treatment with anakinra resulted in good control of the disease. CONCLUSION: We identified the novel gain-of-function p.Gln636Glu NLRP3 mutation, which was detected as a somatic mutation restricted to myeloid cells, as the cause of late-onset but otherwise typical CAPS. Our results expand the diversity of CAPS toward milder phenotypes than previously reported, including those starting during adulthood. PMID- 27273850 TI - In vivo monitoring of topical therapy for acne with reflectance confocal microscopy. AB - BACKGROUND: Acne vulgaris is a common disease of the pilosebaceous unit. The aim of the study was to evaluate compartment-specific treatment action through the microscopic non-invasive imaging of skin changes. METHODS: Mild-moderate acne patients, that were prescribed a topical anti-acne product, were followed by clinical and reflectance confocal microscopy (RCM) imaging every 14 days to 6 weeks. Mean and standard deviation of the scores were analyzed for each time point. RESULTS: After 2 weeks, the RCM count of papules/pustules and the RCM scores of exocytosis and dermal inflammation, decreased substantially. After 4 weeks, the RCM number of comedos was reduced. After 6 weeks, the number of regular follicles increased, while the infundibula with thickened bright border decreased significantly. CONCLUSION: The progressive reduction in the clinical scores was correlated with the improvement of the RCM parameters. RCM study of acne skin showed a different timing for inflammatory and hyperkeratotic components to achieve a significant reduction during topical therapy with the association of retinoid and antibacterial molecules. The microscopic changes observed showed the regularization of the skin and the improvement of acne related features. RCM may represent a useful tool for the objective assessment of treatment efficacy and individual response evaluation. PMID- 27273853 TI - The surgeon as a risk factor: the need for shared individual outcome reports and quality improvement strategies. PMID- 27273851 TI - Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Study Cohorts. AB - OBJECTIVE: Moderate alcohol consumption has antiinflammatory properties and is associated with reduced cardiovascular disease and rheumatoid arthritis risks. We investigated the association between alcohol consumption and systemic lupus erythematosus (SLE) risk among women followed in the Nurses' Health Study (NHS) cohorts. METHODS: We conducted a prospective cohort analysis among 204,055 women in NHS (1980-2012) and NHSII (1989-2011) who were free of connective tissue disease and provided alcohol information at baseline. Alcohol consumption was assessed using a semiquantitative food frequency questionnaire every 2-4 years. We validated incident SLE through medical record review after self-report. Cox proportional hazards models estimated hazard ratios (HRs) for SLE based on cumulative average alcohol intake, adjusting for potential confounders. Results were meta-analyzed using DerSimonian and Laird random-effects models. We further investigated SLE risk associated with wine, beer, and liquor intake. RESULTS: We identified 125 incident SLE cases in NHS and 119 in NHSII. Mean +/- SD age at SLE diagnosis was 55.8 +/- 9.5 years in NHS and 43.4 +/- 7.7 years in NHSII. Compared to no alcohol intake, the meta-analyzed multivariable HR for cumulative alcohol consumption >=5 gm/day was 0.61 (95% confidence interval [95% CI] 0.41-0.89). When limiting alcohol exposure to >4 years prior to SLE diagnosis, the multivariable HR was similar: 0.61 (95% CI 0.41-0.91). Women who drank >=2 servings/week of wine had significantly decreased SLE risk (HR 0.65, 95% CI 0.45 0.96) compared to women who did not drink wine. CONCLUSION: In these large prospective cohorts, we demonstrated an inverse association between moderate alcohol consumption (>=5 grams or 0.5 drink/day) and SLE risk in women. PMID- 27273855 TI - A special look at Outcomes. PMID- 27273854 TI - Compliance with enhanced recovery after surgery criteria and preoperative and postoperative counselling reduces length of hospital stay in colorectal surgery: results of a randomized controlled trial. AB - AIM: The aim of this randomized clinical trial was to compare patients treated using a multimodal approach [enhanced recovery after surgery (ERAS)], with a special focus on counselling, to patients treated in a standard conventional care pathway, who underwent elective colorectal resection. METHOD: In a single-centre trial, adult patients eligible for open or laparoscopic colorectal resection were randomized to an ERAS programme or standard care. The primary end-point was postoperative total hospital stay. Identical discharge criteria were defined for both treatment groups. Secondary end-points included postoperative complications, postoperative C-reactive protein levels, postoperative hospital stay, readmission rate and mortality. All parameters were recorded before operation, on the day of surgery and daily thereafter until discharge. RESULTS: Total hospital stay was significantly shorter among patients randomized to ERAS than among the standard group [median 5 days (range 2-50 days) vs median 8 days (range 2-48 days); P = 0.001]. The two treatment groups exhibited similar outcomes regarding overall major and minor morbidity, reoperation rate, readmission rate and 30-day mortality. There were also no differences in tolerance of enteral nutrition or in the inflammatory response, as reflected by postoperative C-reactive protein levels. CONCLUSION: ERAS care was associated with a significantly shorter length of hospital stay. Without any difference in surgical or general complications, tolerance of enteral nutrition or postoperative C-reactive protein levels, peri operative information and guidance for ensuring that patients comply with the ERAS approach appear to be important factors to reduce the length of hospital stay. PMID- 27273858 TI - Asthma in adolescence: Is there any news? AB - Asthma is a chronic disease that has a significant impact quality of life, which is particularly important in adolescence. We will discuss aspects of epidemiology, the clinical spectrum, diagnostics, and management of asthma in adolescence. In particular, we will highlight the psychological implications of having asthma during this developmental period. Data published in the past 10 years, since we last reviewed the subject, will be the main focus of this paper. The care of the teenager with asthma should take into account the rapid physical, emotional, cognitive, and social changes that occur during normal adolescence. The diagnostic process may be more difficult since teenagers tend to deny their illness. Thus, both under-diagnosis and under-assessment of asthma severity may lead to under-treatment and potentially avoidable morbidity and even mortality. Conversely, teenagers may be often misdiagnosed as having asthma or their asthma severity may be overestimated leading to inappropriate and sometimes excessive treatment. Educational programs, environmental avoidance measures, proper use of medications along with a skilled approach, and a caring attitude of health providers are all very important for successful management. Pediatr Pulmonol. 2017;52:129-138. (c) 2016 Wiley Periodicals, Inc. PMID- 27273859 TI - Directional Clustering of Slanted Nanopillars by Elastocapillarity. AB - The unidirectional clustering induced by capillary force of drying liquids between pillars is investigated and a theoretical model to set a criterion of the unidirectional clustering of the slanted nanopillars is proposed. PMID- 27273860 TI - Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke. AB - OBJECTIVE: It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open label study (NCT01183533) in patients with wake-up stroke (WUS). METHODS: We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18 to 80 years of age, National Institutes of Health Stroke Scale (NIHSS) <=25, and selected only on the appearance of noncontrast computed tomography (ie, over one third middle cerebral artery territory hypodensity). Standard-dose (0.9mg/kg) intravenous rtPA had to be started <=3 hours of patient awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (sICH) with preplanned stopping rules and data safety board oversight. Other endpoints included: asymptomatic intracerebral hemorrhage; clinical improvement in NIHSS; and 90-day modified Rankin Scale (mRS) score. RESULTS: Between October 2010 and October 2013, all 40 preplanned patients were enrolled (50% men) at five stroke centers. Four patients (10%) were subsequently determined to be mimics. Patients had a mean age of 60.8, median NIHSS of 6.5 (range, 2-24), and received thrombolysis at a mean time of 10.3 +/- 2.6 LSN and 2.6 +/- 0.6 hours from awakening with deficits. No sICH or parenchymal hematomas occurred. At 3 months, 20 of 38 (52.6%) patients achieved excellent recovery with mRS scores of 0 or 1 (2 patients were lost to follow-up). INTERPRETATION: Intravenous thrombolysis was safe in this prospective WUS study of patients selected by noncontrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design. Ann Neurol 2016;80:211-218. PMID- 27273862 TI - Multifunctional Nanoparticles Self-Assembled from Small Organic Building Blocks for Biomedicine. AB - Supramolecular self-assembly shows significant potential to construct responsive materials. By tailoring the structural parameters of organic building blocks, nanosystems can be fabricated, whose performance in catalysis, energy storage and conversion, and biomedicine has been explored. Since small organic building blocks are structurally simple, easily modified, and reproducible, they are frequently employed in supramolecular self-assembly and materials science. The dynamic and adaptive nature of self-assembled nanoarchitectures affords an enhanced sensitivity to the changes in environmental conditions, favoring their applications in controllable drug release and bioimaging. Here, recent significant research advancements of small-organic-molecule self-assembled nanoarchitectures toward biomedical applications are highlighted. Functionalized assemblies, mainly including vesicles, nanoparticles, and micelles are categorized according to their topological morphologies and functions. These nanoarchitectures with different topologies possess distinguishing advantages in biological applications, well incarnating the structure-property relationship. By presenting some important discoveries, three domains of these nanoarchitectures in biomedical research are covered, including biosensors, bioimaging, and controlled release/therapy. The strategies regarding how to design and characterize organic assemblies to exhibit biomedical applications are also discussed. Up-to-date research developments in the field are provided and research challenges to be overcome in future studies are revealed. PMID- 27273863 TI - A pilot randomized clinical trial assessing the effect of cricoid pressure on risk of aspiration. AB - INTRODUCTION: Patients at risk for microaspiration during elective intubation often receive cricoid pressure in the hopes of mitigating such risk. However, there is scarce evidence to either support or reject this practice. The objective of this investigation was to assess the effect of cricoid pressure on microaspiration and to inform the potential feasibility of conducting a larger, more definitive clinical trial. METHODS: This was a pilot randomized clinical trial set in the operating rooms of a tertiary referral hospital between August and October of 2014. Patients with risk factors for microaspiration (obesity, gastroesophageal reflux disease, or diabetes) were enrolled. The patients were randomized to either cricoid pressure or no cricoid pressure during induction of anesthesia with endotracheal intubation. Immediately after intubation, a sample of lower airway secretions was collected and analyzed for pepsin A. MAIN RESULTS: A total of 95 patients were evaluated, randomized and completed the study protocol. 46 were randomized to cricoid pressure and 49 to no cricoid pressure. Seven patients crossed-over treatment arms. A total of 18 (19.6%) patients met the pre-defined criteria for microaspiration. In both the intention-to-treat and per-protocol analyses, there were no statistically significant differences in the rate of microaspiration [OR (95% CI)] = 1.39 (0.49-3.92) and 1.30 (0.44-3.86), respectively. CONCLUSIONS: Utilizing pepsin A as a biomarker of aspiration, this pilot clinical trial did not find evidence for a reduced rate of aspiration or adverse clinical events with the administration of cricoid pressure during elective endotracheal intubation of patients with risk factors for microaspiration. PMID- 27273864 TI - Neuronal Nogo-A in New-born Retinal Ganglion Cells: Implication for the Formation of the Age-related Fiber Order in the Optic Tract. AB - Nogo-A is highly expressed in oligodendrocytes in the adult central nervous system (CNS). Recently it was found that Nogo-A is also expressed in some neuronal types during development. Here, we examined the expression pattern of Nogo-A in both the retina and optic tract (OT) of mouse embryos from E12 to E15. After perturbation of its function in the OT for 5 hr in the brain slice culture system using a Nogo-A specific antibody or antagonist of its receptor (NEP1-40), the optic nerve fibers and growth cones were traced with DiI. We showed that most Tuj-1 positive new-born neurons at E12 were Nogo-A positive. At E15, retinal neurons reduced the Nogo-A expression. It was worth noting that some projecting axons expressed Nogo-A along the retinofugal pathway. On the basis of their specific locations within the superficial half of the OT and the colocalization with GAP-43 (a marker for the newly born growth cones and axons), we concluded that those Nogo-A positive axons were the newly arrived retinal fibers. Blocking the function of Nogo-A with Nogo-A antibody or NEP1-40 resulted in the shift of DiI labeled axons and growth cones from the superficial half to the whole depth of the OT. These results indicate that Nogo-A in the newly born retinal ganglion cells (RGCs) and their axons are involved in sorting out the newly arrived axons to the subpial region of the OT. Anat Rec, 299:1027-1036, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27273865 TI - KSR1 and EPHB4 Regulate Myc and PGC1beta To Promote Survival of Human Colon Tumors. AB - Identification and characterization of survival pathways active in tumor cells but absent in normal tissues provide opportunities to develop effective anticancer therapies with reduced toxicity to the patient. We show here that, like kinase suppressor of Ras 1 (KSR1), EPH (erythropoietin-producing hepatocellular carcinoma) receptor B4 (EPHB4) is aberrantly overexpressed in human colon tumor cell lines and selectively required for their survival. KSR1 and EPHB4 support tumor cell survival by promoting the expression of downstream targets, Myc and the transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1beta (PGC1beta). While KSR1 promotes the aberrant expression of Myc and the PGC1beta protein via a posttranscriptional mechanism, EPHB4 has a greater effect on Myc and PGC1beta expression via its ability to elevate mRNA levels. Subsequent analysis of the posttranscriptional regulation demonstrated that KSR1 promotes the translation of Myc protein. These findings reveal novel KSR1- and EPHB4-dependent signaling pathways supporting the survival of colorectal cancer cells through regulation of Myc and PGC1beta, suggesting that inhibition of KSR1 or EPHB4 effectors may lead to selective toxicity in colorectal tumors. PMID- 27273866 TI - Coordinated Action of Nap1 and RSC in Disassembly of Tandem Nucleosomes. AB - The SWI/SNF and RSC family of ATP-dependent chromatin remodelers disassembles nucleosomes by moving nucleosomes into the vicinity of adjoining nucleosomes. We found that the histone chaperone Nap1 efficiently promotes disassembly of adjacent nucleosomes with which RSC collides and not the disassembly of nucleosomes mobilized by RSC. Nap1 is specific to RSC, as it does not target SWI/SNF, its paralog in Saccharomyces cerevisiae Extensive mutational analysis of Nap1 has revealed that Nap1 affinity for histones H2A-H2B and H3-H4 and its ability to displace histones from DNA are required for Nap1 to enhance RSC mediated disassembly. Other histone chaperones, such as Vps75, that also bind histones are not able to enhance RSC-mediated disassembly. Our study suggests a mechanism by which Nap1 is recruited to actively transcribed regions and assists in the passage of the transcription complex through chromatin, and it provides a novel mechanism for the coordinated action of RSC and Nap1. PMID- 27273868 TI - Antifungal therapy: drug-drug interactions at your fingertips-authors' response. PMID- 27273870 TI - A 26-Year-Old Woman With Asthma and Bilateral Ocular Swelling. PMID- 27273871 TI - Interactive anatomical and surgical live stream lectures improve students' academic performance in applied clinical anatomy. AB - Tuebingen's Sectio Chirurgica (TSC) is an innovative, interactive, multimedia, and transdisciplinary teaching method designed to complement dissection courses. The Tuebingen's Sectio Chirurgica (TSC) allows clinical anatomy to be taught via interactive live stream surgeries moderated by an anatomist. This method aims to provide an application-oriented approach to teaching anatomy that offers students a deeper learning experience. A cohort study was devised to determine whether students who participated in the TSC were better able to solve clinical application questions than students who did not participate. A total of 365 students participated in the dissection course during the winter term of the 2012/2013 academic year. The final examination contained 40 standard multiple choice (S-MC) and 20 clinically-applied multiple-choice (CA-MC) items. The CA-MC items referred to clinical cases but could be answered solely using anatomical knowledge. Students who regularly participated in the TSC answered the CA-MC questions significantly better than the control group (75% and 65%, respectively; P < 0.05, Mann-Whitney U test). The groups exhibited no differences on the S-MC questions (85% and 82.5%, respectively; P > 0.05). The CA-MC questions had a slightly higher level of difficulty than the S-MC questions (0.725 and 0.801, respectively; P = 0.083). The discriminatory power of the items was comparable (S MC median Pearson correlations: 0.321; CA-MC: 0.283). The TSC successfully teaches the clinical application of anatomical knowledge. Students who attended the TSC in addition to the dissection course were able to answer CA-MC questions significantly better than students who did not attend the TSC. Thus, attending the TSC in addition to the dissection course supported students' clinical learning goals. Anat Sci Educ 10: 46-52. (c) 2016 American Association of Anatomists. PMID- 27273872 TI - Cancer risk of sulfonylureas in patients with type 2 diabetes mellitus: A systematic review. AB - BACKGROUND: Increasing evidence suggests that oral hypoglycemic agents used in type 2 diabetes mellitus (T2DM) may affect cancer risk. Sulfonylureas (SUs) are the most frequently used antidiabetic medications for T2DM. Whether using SUs has any effect on cancer has received considerable attention. The aim of this study was to assess the effects of SUs on cancer risk in T2DM patients. METHODS: Published studies were identified in PubMed, EMBASE, and the Cochrane Register of Clinical Studies, and ClinicalTrials.gov was searched for additional information to identify randomized controlled trials (RCTs), cohort studies, and case-control studies. The abstracts and full text were screened, data collected, and the risk of bias assessed for each individual study. RESULTS: Seventy-seven studies (33 RCTs, 27 cohort studies, and 17 case-control studies) were analyzed. The RCTs did not report a difference in the risk of malignant tumor between SU-treated T2DM patients and controls (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.78 1.18); cohort studies showed that cancer risk was higher in patients using SUs than metformin (relative risk 1.60 [95%CI 1.37-1.87]; adjusted hazard ratio 1.13 [95%CI 1.06-1.19]), and case-control studies suggested a trend for increased cancer risk in those using SUs compared with non-SU users (adjusted OR 1.13; 95%CI 0.93-1.37). CONCLUSIONS: The available evidence clearly shows that SUs can significantly increase the risk of cancer compared with metformin. Although the evidence suggests the possibility that SU users may have a higher risk of cancer than those using alternative medications in addition to metformin, it remains inadequate to enable definitive conclusions to be drawn. PMID- 27273869 TI - 2016 Comprehensive Update of the Banff Working Group on Liver Allograft Pathology: Introduction of Antibody-Mediated Rejection. AB - The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included. PMID- 27273873 TI - Apoptotic Process Induced by Oxaliplatin in Rat Hippocampus Causes Memory Impairment. AB - Aspects of memory involved in cognitive mechanisms were investigated in rat after oxaliplatin (OX) chemotherapy using animal behavioural assessment of passive avoidance and social learning paradigms, which are both hippocampus-sensitive. Rodents, previously subjected to 2-week OX treatment, showed passive avoidance and social learning impairment and apoptotic processes in the hippocampus. Apoptosis rate significantly increased in cultured hippocampal cells exposed to OX at increasing doses, and this effect was dose-dependent. Ex vivo experiments showed that cell damage and apoptosis were blocked in the hippocampus from OX rats cotreated with copper sulphate (CS) which precludes OX transport inside the cell. In vivo, passive avoidance and social learning impairment could not be observed in OX rats co-administered with CS. Thus, a site of action of OX treatment on memory impairment appears to be located at the hippocampus. These findings strongly support that cellular damage induced by OX in rodent hippocampus underlies the weakening of some memory functions. PMID- 27273874 TI - End-inspiratory molar mass step correction for analysis of infant multiple breath washout tests. AB - A refined software algorithm was recently proposed for the analysis of infant multiple breath washout (MBW) measurements. The proposed algorithm uses the change in end-inspiratory molar mass between the wash-in and wash-out curves (EIMM-step) to define the required step response correction of the MM signal and is assumed to provide an accurate evaluation of complete washout of the tracer gas, in comparison to the current software algorithm which applies the change in end-expiratory molar mass (EEMM)-step. We aimed to evaluate the use of the EIMM step method in a broad range of infants. We performed retrospective analyses comparing the EIMM- and EEMM-step change methods in MBW data collected from infants with cystic fibrosis (CF), infants born preterm, and healthy infants using an ultrasonic flowmeter. We found that the EIMM-step correction significantly increased LCI and functional residual capacity (FRC) in infants with CF, preterm infants, and healthy infants compared with the EEMM-step method. In addition, more than half the measurements that were technically acceptable and repeatable using the EEMM-step correction in healthy infants were excluded after using the EIMM-step correction. We found a large difference between the EIMM- and EEMM-steps in healthy infants indicating incomplete washout, suggesting the need for a longer washout time with using the EIMM-step analysis method. The data indicates that the EIMM-step analysis method may have the potential to generate false abnormal LCI values in individuals without lung disease. Revised normative data may be required if this method is universally adopted. Pediatr Pulmonol. 2017;52:10-13. (c) 2016 Wiley Periodicals, Inc. PMID- 27273875 TI - Methylene Homologues of Artemisone: An Unexpected Structure-Activity Relationship and a Possible Implication for the Design of C10-Substituted Artemisinins. AB - We sought to establish if methylene homologues of artemisone are biologically more active and more stable than artemisone. The analogy is drawn with the conversion of natural O- and N-glycosides into more stable C-glycosides that may possess enhanced biological activities and stabilities. Dihydroartemisinin was converted into 10beta-cyano-10-deoxyartemisinin that was hydrolyzed to the alpha primary amide. Reduction of the beta-cyanide and the alpha-amide provided the respective methylamine epimers that upon treatment with divinyl sulfone gave the beta- and alpha-methylene homologues, respectively, of artemisone. Surprisingly, the compounds were less active in vitro than artemisone against P. falciparum and displayed no appreciable activity against A549, HCT116, and MCF7 tumor cell lines. This loss in activity may be rationalized in terms of one model for the mechanism of action of artemisinins, namely the cofactor model, wherein the presence of a leaving group at C10 assists in driving hydride transfer from reduced flavin cofactors to the peroxide during perturbation of intracellular redox homeostasis by artemisinins. It is noted that the carba analogue of artemether is less active in vitro than the O-glycoside parent toward P. falciparum, although extrapolation of such activity differences to other artemisinins at this stage is not possible. However, literature data coupled with the leaving group rationale suggest that artemisinins bearing an amino group attached directly to C10 are optimal compounds. PMID- 27273877 TI - Self-Powered UV-Near Infrared Photodetector Based on Reduced Graphene Oxide/n-Si Vertical Heterojunction. AB - A novel self-powered photodetector based on reduced graphene oxide (rGO)/n-Si p-n vertical heterojunction with high sensitivity and fast response time is presented. The photodetector contains a p-n vertical heterojunction between a drop-casted rGO thin film and n-Si. Contacts between the semiconductor layer (rGO, n-Si) and source-drain Ti/Au electrodes allow efficient transfer of photogenerated charge carriers. The self-powered UV-near infrared photodetector shows high sensitivity toward a spectrum of light from 365 to 1200 nm. Under the 600 nm illumination (0.81 mW cm-2 ), the device has a photoresponsivity of 1.52 A W-1 , with fast response and recover time (2 ms and 3.7 ms), and the ON/OFF ratios exceed 104 when the power density reaches ~2.5 mW cm-2 . The high photoresponse primarily arises from the built-in electric field formed at the interface of n-Si and rGO film. The effect of rGO thickness, rGO reduction level, and layout of rGO/n-Si effective contact area on device performance are also systematically investigated. PMID- 27273878 TI - Students helping students: Five years of experience. PMID- 27273876 TI - Elevated IgA Plasmablast Levels in Subjects at Risk of Developing Rheumatoid Arthritis. AB - OBJECTIVE: The disease process in rheumatoid arthritis (RA) starts years before the clinical diagnosis is made, and elevated levels of disease-specific autoantibodies can be detected during this period. Early responses to known or novel autoantigens likely drive the eventual production of pathogenic autoimmunity. Importantly, the presence of disease-specific autoantibodies can identify individuals who are at high risk of developing RA but who do not currently have arthritis. The goal of the current study was to characterize plasmablasts from individuals at risk of developing RA. METHODS: We investigated antibody-secreting plasmablasts derived from a well-characterized cohort of individuals who were at risk of developing RA, based on RA-related serum autoantibody positivity, as compared to patients with early (<1 year) seropositive RA as well as healthy control subjects. The plasmablast antibody repertoires of at-risk subjects were analyzed using DNA barcode-based methods with paired heavy- and light-chain gene sequencing. Cells were single-cell sorted, the cell- and plate-specific DNA barcodes were sequentially added, and next-generation sequencing was performed. RESULTS: Total plasmablast levels were similar in the antibody-positive (1%) and control (0.4-1.6%) groups. However, increased frequencies of IgA+ versus IgG+ plasmablasts were observed in the antibody-positive group (39% IgA+ and 37% IgG+) as compared to other groups (1-9% IgA+ and 71-87% IgG+). Paired antibody sequences from antibody-positive subjects revealed cross-isotype clonal families and similar sequence characteristics in the IgA and IgG plasmablast repertoires. Antibody-positive individuals also demonstrated elevated serum levels of IgA isotype anti-cyclic citrullinated peptide 3 antibodies. CONCLUSION: The IgA plasmablast dominance in these antibody positive individuals suggests that a subset of RA-related autoantibodies may arise from mucosal immune responses and may be involved in early disease pathogenesis in individuals who are at risk of developing RA. PMID- 27273879 TI - Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial. AB - Loss of muscle mass is associated with increased risk of morbidity and mortality in hospitalized patients. Uncertainties of treatment efficiency by short-term artificial nutrition remain, specifically improvement of protein balance in skeletal muscles. In this study, algorithmic microarray analysis was applied to map cellular changes related to muscle protein metabolism in human skeletal muscle tissue during provision of overnight preoperative total parenteral nutrition (TPN). Twenty-two patients (11/group) scheduled for upper GI surgery due to malignant or benign disease received a continuous peripheral all-in-one TPN infusion (30 kcal/kg/day, 0.16 gN/kg/day) or saline infusion for 12 h prior operation. Biopsies from the rectus abdominis muscle were taken at the start of operation for isolation of muscle RNA RNA expression microarray analyses were performed with Agilent Sureprint G3, 8 * 60K arrays using one-color labeling. 447 mRNAs were differently expressed between study and control patients (P < 0.1). mRNAs related to ribosomal biogenesis, mRNA processing, and translation were upregulated during overnight nutrition; particularly anabolic signaling S6K1 (P < 0.01-0.1). Transcripts of genes associated with lysosomal degradation showed consistently lower expression during TPN while mRNAs for ubiquitin-mediated degradation of proteins as well as transcripts related to intracellular signaling pathways, PI3 kinase/MAPkinase, were either increased or decreased. In conclusion, muscle mRNA alterations during overnight standard TPN infusions at constant rate altered mRNAs associated with mTOR signaling; increased initiation of protein translation; and suppressed autophagy/lysosomal degradation of proteins. This indicates that overnight preoperative parenteral nutrition is effective to promote muscle protein metabolism. PMID- 27273880 TI - Urea transporters and sweat response to uremia. AB - In humans, urea is excreted in sweat, largely through the eccrine sweat gland. The urea concentration in human sweat is elevated when compared to blood urea nitrogen. The sweat urea nitrogen (UN) of patients with end-stage kidney disease (ESRD) is increased when compared with healthy humans. The ability to produce sweat is maintained in the overwhelming majority of ESRD patients. A comprehensive literature review found no reports of sweat UN neither in healthy rodents nor in rodent models of chronic kidney disease (CKD). Therefore, this study measured sweat UN concentrations in healthy and uremic rats. Uninephrectomy followed by renal artery ligation was used to remove 5/6 of renal function. Rats were then fed a high-protein diet to induce uremia. Pilocarpine was used to induce sweating. Sweat droplets were collected under oil. Sweat UN was measured with a urease assay. Serum UN was measured using a fluorescent ortho pthalaldehyde reaction. Immunohistochemistry (IHC) was accomplished with a horseradish peroxidase and diaminobenzidine technique. Sweat UN in uremic rats was elevated greater than two times compared to healthy pair-fed controls (220 +/ 17 and 91 +/- 15 mmol/L, respectively). Post hoc analysis showed a significant difference between male and female uremic sweat UN (279 +/- 38 and 177 +/- 11 mmol/L, respectively.) IHC shows, for the first time, the presence of the urea transporters UT-B and UT-A2 in both healthy and uremic rat cutaneous structures. Future studies will use this model to elucidate how rat sweat UN and other solute excretion is altered by commonly prescribed diuretics. PMID- 27273881 TI - Alteration of cardiac autonomic function in patients with newly diagnosed epilepsy. AB - The aim of the study was to determine if heart rate variability (HRV) showed any changes in patients with newly diagnosed epilepsy in comparison with controls. Sixty-five patients with epilepsy (38 males and 27 females), aged 30-50 years, who had never previously received treatment with antiepileptic drugs were eligible for inclusion in this study. Resting electrocardiogram (ECG) at spontaneous respiration was recorded for 5 min in supine position. Time-domain analysis, frequency-domain analysis, and Poincare plot of HRV were recorded from ECG In time-domain measures, the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD) and percentage of consecutive RR intervals that differ by more than 50 msec (pNN50) were significantly less in patients with epilepsy. In frequency-domain measures, high frequency [(HF) msec(2)], HF (nu), and low frequency [LF (msec(2))] were significantly less in patients with epilepsy while LF (nu) and LF/HF were significantly high in patients with epilepsy. In Poincare plot, standard deviation perpendicular to line of Poincare plot (SD1) and standard deviation along the line of entity in Poincare plot (SD2) were significantly less in patients with epilepsy. Our results suggest that epileptic patients have an impact on the cardiac autonomic function as measured by HRV. PMID- 27273882 TI - Unexpected severe consequences of Pikfyve deletion by aP2- or Aq-promoter-driven Cre expression for glucose homeostasis and mammary gland development. AB - Systemic deficiency of PIKfyve, the evolutionarily conserved phosphoinositide kinase synthesizing cellular PtdIns5P and PtdIns(3,5)P2 and implicated in insulin signaling, causes early embryonic death in mice. In contrast, mice with muscle specific Pikfyve disruption have normal lifespan but exhibit early-age whole-body glucose intolerance and muscle insulin resistance, thus establishing the key role of muscle PIKfyve in glucose homeostasis. Fat and muscle tissues control postprandial glucose clearance through different mechanisms, raising questions as to whether adipose Pikfyve disruption will also trigger whole-body metabolic abnormalities, and if so, what the mechanism might be. To clarify these issues, here we have characterized two new mouse models with adipose tissue disruption of Pikfyve through Cre recombinase expression driven by adipose-specific aP2- or adiponectin (Aq) promoters. Whereas both mouse lines were ostensibly normal until adulthood, their glucose homeostasis and systemic insulin sensitivity were severely dysregulated. These abnormalities stemmed in part from accelerated fat cell lipolysis and elevated serum FFA Intriguingly, aP2-Cre-PIKfyve(fl/fl) but not Aq-Cre-PIKfyve(fl/fl) females had severely impaired pregnancy-induced mammary gland differentiation and lactogenesis, consistent with aP2-Cre-mediated Pikfyve excision in nonadipogenic tissues underlying this defect. Intriguingly, whereas mammary glands from postpartum control and Aq-Cre-PIKfyve(fl/fl) mice or ex vivo mammary gland explants showed profound upregulation of PIKfyve protein levels subsequent to prolactin receptor activation, such increases were not apparent in aP2-Cre-PIKfyve(fl/fl) females. Collectively, our data identify for the first time that adipose tissue Pikfyve plays a key role in the mechanisms regulating glucose homeostasis and that the PIKfyve pathway is critical in mammary epithelial differentiation during pregnancy and lactogenesis downstream of prolactin receptor signaling. PMID- 27273883 TI - Gastrointestinal transport of calcium and glucose in lactating ewes. AB - During lactation, mineral and nutrient requirements increase dramatically, particularly those for Ca and glucose. In contrast to monogastric species, in ruminants, it is rather unclear to which extend this physiological change due to increased demand for milk production is accompanied by functional adaptations of the gastrointestinal tract (GIT). Therefore, we investigated potential modulations of Ca and glucose transport mechanisms in the GIT of lactating and dried-off sheep. Ussing-chamber technique was applied to determine the ruminal and jejunal Ca flux rates. In the jejunum, electrophysiological properties in response to glucose were recorded. Jejunal brush-border membrane vesicles (BBMV) served to characterize glucose uptake via sodium-linked glucose transporter 1 (SGLT1), and RNA and protein expression levels of Ca and glucose transporting systems were determined. Ruminal Ca flux rate data showed a trend for higher absorption in lactating sheep. In the jejunum, small Ca absorption could only be observed in lactating ewes. From the results, it may be assumed that lactating ewes compensate for the Ca loss by increasing bone mobilization rather than by increasing supply through absorption from the GIT Presence of SGLT1 in the jejunum of both groups was shown by RNA and protein identification, but glucose uptake into BBMV could only be detected in lactating sheep. This, however, could not be attributed to electrogenic glucose absorption in lactating sheep under Ussing-chamber conditions, providing evidence that changes in jejunal glucose uptake may include additional factors, that is, posttranslational modifications such as phosphorylation. PMID- 27273885 TI - Repetitive flanking sequences challenge microsatellite marker development: a case study in the lepidopteran Melanargia galathea. AB - Microsatellite DNA families (MDF) are stretches of DNA that share similar or identical sequences beside nuclear simple-sequence repeat (nSSR) motifs, potentially causing problems during nSSR marker development. Primers positioned within MDFs can bind several times within the genome and might result in multiple banding patterns. It is therefore common practice to exclude MDF loci in the course of marker development. Here, we propose an approach to deal with multiple primer-binding sites by purposefully positioning primers within the detected repetitive element. We developed a new protocol to determine the family type and the primer position in relation to MDFs using the software packages repark and repeatmasker together with an in-house R script. We re-evaluated newly developed nSSR markers for the lepidopteran Marbled White (Melanargia galathea) and explored the implications of our results with regard to published data sets of the butterfly Euphydryas aurinia, the grasshopper Stethophyma grossum, the conifer Pinus cembra and the crucifer Arabis alpina. For M. galathea, we show that it is not only possible to develop reliable nSSR markers for MDF loci, but even to benefit from their presence in some cases: We used one unlabelled primer, successfully binding within an MDF, for two different loci in a multiplex PCR, combining this family primer with uniquely binding and fluorescently labelled primers outside of MDFs, respectively. As MDFs are abundant in many taxa, we propose to consider these during nSSR marker development in taxa concerned. Our new approach might help in reducing the number of tested primers during nSSR marker development. PMID- 27273884 TI - Effects of exercise mode, energy, and macronutrient interventions on inflammation during military training. AB - Load carriage (LC) exercise may exacerbate inflammation during training. Nutritional supplementation may mitigate this response by sparing endogenous carbohydrate stores, enhancing glycogen repletion, and attenuating negative energy balance. Two studies were conducted to assess inflammatory responses to acute LC and training, with or without nutritional supplementation. Study 1: 40 adults fed eucaloric diets performed 90-min of either LC (treadmill, mean +/- SD 24 +/- 3 kg LC) or cycle ergometry (CE) matched for intensity (2.2 +/- 0.1 VO2peak L min(-1)) during which combined 10 g protein/46 g carbohydrate (223 kcal) or non-nutritive (22 kcal) control drinks were consumed. Study 2: 73 Soldiers received either combat rations alone or supplemented with 1000 kcal day( 1) from 20 g protein- or 48 g carbohydrate-based bars during a 4-day, 51 km ski march (~45 kg LC, energy expenditure 6155 +/- 515 kcal day(-1) and intake 2866 +/ 616 kcal day(-1)). IL-6, hepcidin, and ferritin were measured at baseline, 3-h post exercise (PE), 24-h PE, 48-h PE, and 72-h PE in study 1, and before (PRE) and after (POST) the 4-d ski march in study 2. Study 1: IL-6 was higher 3-h and 24-h post exercise (PE) for CE only (mode * time, P < 0.05), hepcidin increased 3 h PE and recovered by 48-h, and ferritin peaked 24-h and remained elevated 72-h PE (P < 0.05), regardless of mode and diet. Study 2: IL-6, hepcidin and ferritin were higher (P < 0.05) after training, regardless of group assignment. Energy expenditure (r = 0.40), intake (r = -0.26), and balance (r = -0.43) were associated (P < 0.05) with hepcidin after training. Inflammation after acute LC and CE was similar and not affected by supplemental nutrition during energy balance. The magnitude of hepcidin response was inversely related to energy balance suggesting that eating enough to balance energy expenditure might attenuate the inflammatory response to military training. PMID- 27273886 TI - On Engster's care-justification of the specialness thesis about healthcare. AB - To say health is 'special' is to say that it has a moral significance that differentiates it from other goods (cars, say or radios) and, as a matter of justice, warrants distributing it separately. In this essay, I critique a new justification for the specialness thesis about healthcare (STHC) recently put forth by Engster. I argue that, regrettably, Engster's justification of STHC ultimately fails and fails on much the same grounds as have previous justifications of STHC. However, I also argue that Engster's argument still adds something valuable to the debate around STHC insofar as it reminds us that the moral significance of healthcare may be wider than simply its effect on the incidence of disability and disease: one further reason we may think healthcare is morally significant is because it concerns the treatment and care of those who are already unwell. PMID- 27273888 TI - The Intergenerational Transmission of Suicide: Moral Injury and the Mysterious Object in the Work of Walker Percy. AB - The intrapsychic mechanisms for the intergenerational transmission of suicide are not adequately theorized, though it is well known that a family history of suicide places survivors at increased risk for suicide. The suicide of a family member, particularly a parent, it is hypothesized, marks some survivors with a type of trauma associated with moral injury, which may produce an alteration in object relations with the emergence of what may be called a mysterious object. Under the press of these conditions, survivors may embark on what Apprey (2014) has termed an "urgent errand" in an effort to solve a problem in the anterior generation. Analysands with a history of familial suicide may bring symptoms of moral injury, a mysterious object relation, and a risk for suicide into the transference. The family history, life history, and literary work of the novelist Walker Percy, who had an extensive family history of suicide, provides evidence for the hypothesis linking moral injury, a mysterious object, and an urgent errand in such patients. PMID- 27273887 TI - Why cure, why now? AB - Combination antiretroviral therapy (cART) is highly effective at preventing morbidity and mortality due to infection with human immunodeficiency virus (HIV), but does not eradicate the virus. Consequently, cART must be administered life long. Recent progress has stimulated research towards a cure of HIV infection. Approaches under investigation include hematopoietic stem cell transplantation, latency reactivating agents, immune based therapies, and cell-based therapies. Each of these approaches carries potential risks that must be weighed against the availability of safe and effective cART. Balancing the risks and benefits of this research poses unique challenges to potential study participants, clinicians and investigators. PMID- 27273889 TI - Controlling the time evolution of mAb N-linked glycosylation - Part II: Model based predictions. AB - N-linked glycosylation is known to be a crucial factor for the therapeutic efficacy and safety of monoclonal antibodies (mAbs) and many other glycoproteins. The nontemplate process of glycosylation is influenced by external factors which have to be tightly controlled during the manufacturing process. In order to describe and predict mAb N-linked glycosylation patterns in a CHO-S cell fed batch process, an existing dynamic mathematical model has been refined and coupled to an unstructured metabolic model. High-throughput cell culture experiments carried out in miniaturized bioreactors in combination with intracellular measurements of nucleotide sugars were used to tune the parameter configuration of the coupled models as a function of extracellular pH, manganese and galactose addition. The proposed modeling framework is able to predict the time evolution of N-linked glycosylation patterns during a fed-batch process as a function of time as well as the manipulated variables. A constant and varying mAb N-linked glycosylation pattern throughout the culture were chosen to demonstrate the predictive capability of the modeling framework, which is able to quantify the interconnected influence of media components and cell culture conditions. Such a model-based evaluation of feeding regimes using high-throughput tools and mathematical models gives rise to a more rational way to control and design cell culture processes with defined glycosylation patterns. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1135-1148, 2016. PMID- 27273891 TI - Supporting the Evaluation and Implementation of Musculoskeletal Models of Care: A Globally Informed Framework for Judging Readiness and Success. AB - OBJECTIVE: To develop a globally informed framework to evaluate readiness for implementation and success after implementation of musculoskeletal models of care (MOCs). METHODS: Three phases were undertaken: 1) a qualitative study with 27 Australian subject matter experts (SMEs) to develop a draft framework; 2) an eDelphi study with an international panel of 93 SMEs across 30 nations to evaluate face validity, and refine and establish consensus on the framework components; and 3) translation of the framework into a user-focused resource and evaluation of its acceptability with the eDelphi panel. RESULTS: A comprehensive evaluation framework was developed for judging the readiness and success of musculoskeletal MOCs. The framework consists of 9 domains, with each domain containing a number of themes underpinned by detailed elements. In the first Delphi round, scores of "partly agree" or "completely agree" with the draft framework ranged 96.7%-100%. In the second round, "essential" scores ranged 58.6% 98.9%, resulting in 14 of 34 themes being classified as essential. SMEs strongly agreed or agreed that the final framework was useful (98.8%), usable (95.1%), credible (100%) and appealing (93.9%). Overall, 96.3% strongly supported or supported the final structure of the framework as it was presented, while 100%, 96.3%, and 100% strongly supported or supported the content within the readiness, initiating implementation, and success streams, respectively. CONCLUSION: An empirically derived framework to evaluate the readiness and success of musculoskeletal MOCs was strongly supported by an international panel of SMEs. The framework provides an important internationally applicable benchmark for the development, implementation, and evaluation of musculoskeletal MOCs. PMID- 27273892 TI - Characterization of a novel HLA-B*40 allele, HLA-B*40:186:02, by cloning and sequencing. AB - A novel HLA-B*40 variant, HLA-B*40:186:02, has been identified by cloning and sequencing in a southern Chinese Han population. Aligned with HLA-B*40:01:01, HLA B*40:186:02 has a nonsynonymous cytosine mutation at nucleotide position 165 in exon 2, leading to amino acid change from glycine to arginine at codon 56. It differs from HLA-B*40:186:01 by a synonymous change (adenine to cytosine) at position 165 in exon 2. PMID- 27273890 TI - Erosion of Transplantation Tolerance After Infection. AB - Recent clinical studies suggest that operational allograft tolerance can be persistent, but long-term surviving allografts can be rejected in a subset of patients, sometimes after episodes of infection. In this study, we examined the impact of Listeria monocytogenes (Lm) infection on the quality of tolerance in a mouse model of heart allograft transplantation. Lm infection induced full rejection in 40% of tolerant recipients, with the remaining experiencing a rejection crisis or no palpable change in their allografts. In the surviving allografts on day 8 postinfection, graft-infiltrating cell numbers increased and exhibited a loss in the tolerance gene signature. By day 30 postinfection, the tolerance signature was broadly restored, but with a discernible reduction in the expression of a subset of 234 genes that marked tolerance and was down-regulated at day 8 post-Lm infection. We further demonstrated that the tolerant state after Lm infection was functionally eroded, as rejection of the long-term surviving graft was induced with anti-PD-L1 whereas the same treatment had no effect in noninfected tolerant mice. Collectively, these observations demonstrate that tolerance, even if initially robust, exists as a continuum that can be eroded following bystander immune responses that accompany certain infections. PMID- 27273893 TI - Cationic Supramolecular Vesicular Aggregates for Pulmonary Tissue Selective Delivery in Anticancer Therapy. AB - The biopharmaceutical properties of supramolecular vesicular aggregates (SVAs) were characterized with regard to their physicochemical features and compared with cationic liposomes (CLs). Neutral and cationic SVAs were synthesized using two different copolymers of poly(aspartyl hydrazide) by thin-layer evaporation and extrusion techniques. Both copolymers were self-assembled in pre-formulated liposomes and formed neutral and cationic SVAs. Gemcitabine hydrochloride (GEM) was used as an anticancer drug and loaded by a pH gradient remote loading procedure, which significantly increased drug loading inside the SVAs. The resulting average size of the SVAs was 100 nm. The anticancer activity of GEM loaded neutral and cationic SVAs was tested in human alveolar basal epithelial (A549) and colorectal cancer (CaCo-2) cells. GEM-loaded cationic SVAs increased the anticancer activity in A549 and CaCo-2 cells relative to free drug, neutral SVAs, and CLs. In vivo biodistribution in Wistar rats showed that cationic SVAs accumulate at higher concentrations in lung tissue than neutral SVAs and CLs. Cationic SVAs may therefore serve as an innovative future therapy for pulmonary carcinoma. PMID- 27273895 TI - Encapsulation of Single Plasmonic Nanoparticles within ZIF-8 and SERS Analysis of the MOF Flexibility. AB - Hybrid nanostructures composed of metal nanoparticles and metal-organic frameworks (MOFs) have recently received increasing attention toward various applications due to the combination of optical and catalytic properties of nanometals with the large internal surface area, tunable crystal porosity and unique chemical properties of MOFs. Encapsulation of metal nanoparticles of well defined shapes into porous MOFs in a core-shell type configuration can thus lead to enhanced stability and selectivity in applications such as sensing or catalysis. In this study, the encapsulation of single noble metal nanoparticles with arbitrary shapes within zeolitic imidazolate-based metal organic frameworks (ZIF-8) is demonstrated. The synthetic strategy is based on the enhanced interaction between ZIF-8 nanocrystals and metal nanoparticle surfaces covered by quaternary ammonium surfactants. High resolution electron microscopy and tomography confirm a complete core-shell morphology. Such a well-defined morphology allowed us to study the transport of guest molecules through the ZIF-8 porous shell by means of surface-enhanced Raman scattering by the metal cores. The results demonstrate that even molecules larger than the ZIF-8 aperture and pore size may be able to diffuse through the framework and reach the metal core. PMID- 27273894 TI - Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study. AB - OBJECTIVE: To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). METHODS: Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. RESULTS: In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59 1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. CONCLUSION: Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs. PMID- 27273896 TI - Evaluation of the effectiveness of 3D vascular stereoscopic models in anatomy instruction for first year medical students. AB - The head and neck region is one of the most complex areas featured in the medical gross anatomy curriculum. The effectiveness of using three-dimensional (3D) models to teach anatomy is a topic of much discussion in medical education research. However, the use of 3D stereoscopic models of the head and neck circulation in anatomy education has not been previously studied in detail. This study investigated whether 3D stereoscopic models created from computed tomographic angiography (CTA) data were efficacious teaching tools for the head and neck vascular anatomy. The test subjects were first year medical students at the University of Mississippi Medical Center. The assessment tools included: anatomy knowledge tests (prelearning session knowledge test and postlearning session knowledge test), mental rotation tests (spatial ability; presession MRT and postsession MRT), and a satisfaction survey. Results were analyzed using a Wilcoxon rank-sum test and linear regression analysis. A total of 39 first year medical students participated in the study. The results indicated that all students who were exposed to the stereoscopic 3D vascular models in 3D learning sessions increased their ability to correctly identify the head and neck vascular anatomy. Most importantly, for students with low-spatial ability, 3D learning sessions improved postsession knowledge scores to a level comparable to that demonstrated by students with high-spatial ability indicating that the use of 3D stereoscopic models may be particularly valuable to these students with low spatial ability. Anat Sci Educ 10: 34-45. (c) 2016 American Association of Anatomists. PMID- 27273897 TI - Work Ability and Its Related Factors Among Workers in Small and Medium Enterprises: Comparison Among Four ASEAN Countries. AB - Work ability is related to many factors that might influence one's capacity to work. This study aimed to examine the work ability and its related factors among small and medium enterprises (SME) workers in 4 Association of Southeast Asian Nations (ASEAN) countries. The participants in this study included 2098 workers from food and textile industries in Indonesia, Malaysia, Thailand, and Vietnam. A cross-sectional survey of anonymous self-administrated questionnaire was designed to collect information on sociodemographic factors, work environment and ergonomic condition, musculoskeletal disorders, and work ability. Bivariate correlation coefficient and multiple linear regression analyses were used to predict the work ability. Results of this study confirm that work ability in 4 ASEAN countries was similar to that in European countries, and that the sociodemographic factors, work environment and ergonomic condition, and musculoskeletal disorder (MSD) were associated with work ability. These factors are important for considering occupational health and safety policy to promote work ability in food, textile, and other SME workers. PMID- 27273898 TI - Identifying a robust design space for glycosylation during monoclonal antibody production. AB - Glycan distribution has been identified as a "critical quality attribute" for many biopharmaceutical products, including monoclonal antibodies. Consequently, determining quantitatively how process variables affect glycan distribution is important during process development to control antibody glycosylation. In this work, we assess the effect of six bioreactor process variables on the glycan distribution of an IgG1 produced in CHO cells. Our analysis established that glucose and glutamine media concentration, temperature, pH, agitation rate, and dissolved oxygen (DO) had small but significant effects on the relative percentage of various glycans. In addition, we assessed glycosylation enzyme transcript levels and intracellular sugar nucleotide concentrations within the CHO cells to provide a biological explanation for the observed effects on glycan distributions. From these results we identified a robust operating region, or design space, in which the IgG1 could be produced with a consistent glycan distribution. Since our results indicate that perturbations to bioreactor process variables will cause only small (even if significant) changes to the relative percentage of various glycans (<+/-1.5%)-changes that are too small to affect the bioactivity and efficacy of this IgG1 significantly-it follows that the glycan distribution obtained will be consistent even with relatively large variations in bioreactor process variables. However, for therapeutic proteins where bioactivity and efficacy are affected by small changes to the relative percentage of glycans, the same analysis would identify the manipulated variables capable of changing glycan distribution, and hence can be used to implement a glycosylation control strategy. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1149-1162, 2016. PMID- 27273899 TI - Use of new imaging in detecting and monitoring ocular manifestations of the mucopolysaccharidoses. AB - The aim of this review is to summate the eye involvement in patients with mucopolysaccharidoses (MPS) using current ocular imaging techniques, their advantages and disadvantages and how they may aid diagnosis, management and monitoring. We critically reviewed the current literature surrounding MPS and recent imaging technology as well as histology. Primary searches of PubMed and Web of Science were performed. We reviewed all papers on the topic published and summarized the findings of each medical device as well as the advantages and disadvantages of using these for the MPS patient. We discussed the potential of each of these devices to monitor potential ocular pathology in the MPS cohorts in the order of MPS subtype. We reviewed imaging techniques involving use of the Iris Camera, Pentacam, Optical Coherence Tomography (OCT) as well as ultrasound and Heidelberg OCT. The need for reliable objective quantification of eye findings in MPS has led to utilization of new imaging technologies described here, and future use will enhance our understanding of the unique eye features in MPS. In particular, we note that the Pentacam and iris camera are able to provide objective measurements of corneal haze and monitor ocular response to treatment. PMID- 27273900 TI - Antigen-Specificity of T Cell Infiltrates in Biopsies With T Cell-Mediated Rejection and BK Polyomavirus Viremia: Analysis by Next Generation Sequencing. AB - This study interrogates the antigen-specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA-A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell-receptor complementary DNA was performed on peptide-stimulated PBMC and 23 biopsies with T cell-mediated rejection (TCMR) or BKPyVN. Biopsies from patients with BKPyVM or BKVPyVN contained 7.7732 times more alloreactive than virus reactive clones. Biopsies with TCMR also contained BKPyV-specific clones, presumably a manifestation of heterologous immunity. The mean cumulative T cell clonal frequency was 0.1378 for alloreactive clones and 0.0375 for BKPyV-reactive clones. Samples with BKPyVN and TCMR clustered separately in dendrograms of V family and J-gene utilization patterns. Dendrograms also revealed that V-gene, J gene, and D-gene usage patterns were a function of HLA type. In conclusion, biopsies with BKPyVN contain abundant allospecific clones that exceed the number of virus-reactive clones. The T cell component of tissue injury in viral nephropathy appears to be mediated primarily by an "innocent bystander" mechanism in which the principal element is secondary T cell influx triggered by both antiviral and anti-HLA immunity. PMID- 27273901 TI - Trajectories of Low Back Pain From Adolescence to Young Adulthood. AB - OBJECTIVE: Despite the high prevalence and burden of low back pain (LBP), understanding of its course during the transition from adolescence to adulthood is limited. The aim of this study was to identify and describe trajectories of LBP and its impact among a general population sample followed from adolescence to young adulthood. METHODS: Data from followup assessments at years 17, 20, and 22 of the Western Australian Pregnancy Cohort (Raine) Study were used (n = 1,249). Self-reported LBP and its impact on daily life were assessed, and latent class analysis was used to identify clusters. Resultant clusters were profiled on sex, waist circumference, diagnosed comorbid pain, and health-related quality of life. RESULTS: Four clusters were identified: a cluster of participants with a consistently low prevalence of LBP and its impact (53%) during the period from adolescence to young adulthood, a cluster with an increase in the prevalence of LBP and its impact (22%), a cluster with a decrease in the prevalence of LBP and its impact (15%), and a cluster with a consistently high prevalence of LBP and its impact (10%). These clusters differed markedly on the profiling variables. CONCLUSION: The identified clusters provide unique information on LBP and its impact during the transition from adolescence to young adulthood. Consideration of these trajectories could be important in the design of early prevention and management strategies. PMID- 27273902 TI - Characterization of a novel MICA allele, MICA*012:05, by cloning and sequencing. AB - A new MICA allelic variant, MICA*012:05, has been identified in a Chinese Mongolian population. Following polymerase chain reaction-sequence-based typing (PCR-SBT), this new allele was further confirmed by cloning and sequencing. MICA*012:05 was linked to an HLA-A*24-C*01-B*55:02-DRB1*09 haplotype. MICA*012:05 differs from MICA*012:01 by a single synonymous C to T substitution at nucleotide position 269 in exon 3. PMID- 27273903 TI - Association of IgG4-Related Disease With History of Malignancy. AB - OBJECTIVE: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unclear etiology. Some studies suggest that IgG4-RD predisposes patients to malignancy or is a forme fruste of cancer, but we have frequently observed IgG4 RD patients who have a history of malignancy preceding the clinical onset of IgG4 RD. This study was undertaken to characterize IgG4-RD in the setting of previous malignancy diagnosis. METHODS: We identified IgG4-RD patients with a history of invasive malignancy from a well-defined cohort of 125 patients and compared their malignancy history to those of 2 reference groups. First, we calculated a standardized prevalence ratio against general US population estimates from the Surveillance, Epidemiology, and End Results (SEER) database. Second, we identified up to 5 age- and sex-matched controls for each case and calculated the odds of malignancy among those with IgG4-RD compared to controls, using conditional logistic regression. RESULTS: The mean +/- SD age at IgG4-RD onset was 50.3 +/- 14.9 years, and 61% of the patients were male. Twenty (16%) had been diagnosed as having malignancies (total 21 malignancies) before the diagnosis of IgG4-RD. The observed prevalence of malignancy in this cohort was 2.5 times higher (95% confidence interval [95% CI] 1.1-3.6) than expected compared to the SEER database. Compared to matched controls, the frequency of history of malignancy was >3-fold higher in IgG4-RD patients (95% CI 1.6-6.2). CONCLUSION: Our findings suggest that, in a subset of patients with IgG4-RD, malignancy may be associated with subsequent IgG4-RD development. Potential explanations include shared risk factors for both IgG4-RD and cancer, the triggering by cancer of autoantigen expression leading to IgG4-RD, and an increased risk of IgG4-RD resulting from cancer treatment. PMID- 27273904 TI - Circular Dichroism Studies on Plasmonic Nanostructures. AB - In recent years, optical chirality of plasmonic nanostructures has aroused great interest because of innovative fundamental understanding as well as promising potential applications in optics, catalysis and sensing. Herein, state-of-the-art studies on circular dichroism (CD) characteristics of plasmonic nanostructures are summarized. The hybrid of achiral plasmonic nanoparticles (NPs) and chiral molecules is explored to generate a new CD response at the plasmon resonance as well as the enhanced CD intensity of chiral molecules in the UV region, owing to the Coulomb static and dynamic dipole interactions between plasmonic NPs and chiral molecules. As for chiral assembly of plasmonic NPs, plasmon-plasmon interactions between the building blocks are found to induce generation of intense CD response at the plasmon resonance. Three-dimensional periodical arrangement of plasmonic NPs into macroscale chiral metamaterials is further introduced from the perspective of negative refraction and photonic bandgap. A strong CD signal is also discerned in achiral planar plasmonic nanostructures under illumination of circular polarized plane wave at oblique incidence or input vortex beam at normal incidence. Finally perspectives, especially on future investigation of time-resolved CD responses, are presented. PMID- 27273906 TI - YouTube anatomy education: Sources of ethical perplexity. PMID- 27273907 TI - Are We in the Same Risk of Diabetes Mellitus? Gender- and Age-Specific Epidemiology of Diabetes in 2001 to 2014 in the Korean Population. AB - In the early 2000s, the prevalence of diabetes in adults aged >=30 years in Korea was about 9% to 10%, and it remained stable. However, a nationwide survey showed that this prevalence increased over the past few years. After age-standardization using the Korean population of the year 2010, the prevalence of diabetes in adults aged >=30 years was 10.0% to 10.8% between 2001 and 2012, which increased to 12.5% in 2013 and 11.6% in 2014. During that period, there have been changes in the gender- and age-specific prevalence of diabetes in Korean adults. The prevalence of diabetes in the elderly population increased significantly, while this prevalence in young adults, especially in young women, did not change significantly. The contribution of each diabetic risk factor, such as obesity, beta-cell dysfunction, sarcopenia, and socioeconomic status, in developing diabetes has also changed during that period in each gender and age group. For young women, obesity was the most important risk factor; by contrast, for elderly diabetic patients, sarcopenia was more important than obesity as a risk factor. Considering the economic burden of diabetes and its associated comorbidities, a public health policy targeting the major risk factors in each population might be more effective in preventing diabetes. PMID- 27273908 TI - Comparison of the Usefulness of the Updated Homeostasis Model Assessment (HOMA2) with the Original HOMA1 in the Prediction of Type 2 Diabetes Mellitus in Koreans. AB - BACKGROUND: The original homeostasis model assessment (HOMA1) and the updated HOMA model (HOMA2) have been used to evaluate insulin resistance (IR) and beta cell function, but little is known about the usefulness of HOMA2 for the prediction of diabetes in Koreans. The aim of this study was to demonstrate the usefulness of HOMA2 as a predictor of type 2 diabetes mellitus in Koreans without diabetes. METHODS: The study population consisted of 104,694 Koreans enrolled at a health checkup program and followed up from 2001 to 2012. Participants were divided into a normal glucose tolerance (NGT) group and a pre-diabetes group according to fasting glucose and glycosylated hemoglobin levels. Anthropometric and laboratory data were measured at the baseline checkup, and HOMA values were calculated at the baseline and follow-up checkups. The hazard ratios (HRs) of the HOMA1 and HOMA2 values and the prevalence of diabetes at follow-up were evaluated using a multivariable Cox proportional hazards model and Kaplan-Meier analysis. RESULTS: After adjusting for several diabetes risk factors, all of the HOMA values except 1/HOMA1-beta and 1/HOMA2-beta in the NGT group were significant predictors of the progression to diabetes. In the NGT group, there was no significant difference in HOMA1-IR (HR, 1.09; 95% confidence interval [CI], 1.04 to 1.14) and HOMA2-IR (HR, 1.11; 95% CI, 1.04 to 1.19). However, in the pre diabetes group, 1/HOMA2-beta was a more powerful marker (HR, 1.29; 95% CI, 1.26 to 1.31) than HOMA1-IR (HR, 1.23; 95% CI, 1.19 to 1.28) or 1/HOMA1-beta (HR, 1.14; 95% CI, 1.12 to 1.16). In the non-diabetic group (NGT+pre-diabetes), 1/HOMA2-beta was also a stronger predictor of diabetes (HR, 1.27; 95% CI, 1.25 to 1.29) than HOMA1-IR (HR, 1.14; 95% CI, 1.12 to 1.15) or 1/HOMA1-beta (HR, 1.13; 95% CI, 1.11 to 1.14). CONCLUSION: HOMA2 is more predictive than HOMA1 for the progression to diabetes in pre-diabetes or non-diabetic Koreans. PMID- 27273909 TI - Application of the Oral Minimal Model to Korean Subjects with Normal Glucose Tolerance and Type 2 Diabetes Mellitus. AB - BACKGROUND: The oral minimal model is a simple, useful tool for the assessment of beta-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) in humans. METHODS: Plasma glucose, insulin, and C peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10) and T2DM (n=14). The parameters in the computational model were estimated, and the indexes for insulin sensitivity and beta-cell function were compared between the NGT and T2DM groups. RESULTS: The insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of beta-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total beta-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group. CONCLUSION: The oral minimal model can be reproducibly applied to evaluate beta-cell function and insulin sensitivity in Koreans. PMID- 27273910 TI - Comparison of macular pigment and serum lutein concentration changes between free lutein and lutein esters supplements in Japanese subjects. AB - PURPOSE: To compare changes in macular pigment optical density (MPOD) and serum lutein concentration between free lutein and lutein esters supplements in healthy Japanese individuals. METHODS: Twenty healthy subjects (age range, 22-47 years) were recruited into this prospective, randomized, doubled-blind comparative study. Individuals were evenly divided into two groups: free lutein group, supplementation with 10 mg of free lutein; or lutein esters group, supplementation with 20 mg of lutein esters equivalent to 10 mg of free lutein. Each participant took either type of oral lutein daily for 3 months. The serum lutein concentrations and MPOD levels were measured at baseline and 3 and 6 months after the start of supplementation. RESULTS: There were no significant differences in the serum lutein concentrations and MPOD levels at baseline between the groups. The increased serum lutein concentration and MPOD levels at 3 months were respectively, 89% and 38% in the free lutein group and 97% and 17% in the lutein esters group. The serum lutein concentrations in both groups and MPOD levels in the free lutein group increased significantly (p < 0.05) from baseline. No significant differences in serum lutein concentrations and MPOD levels were seen between the groups. Three months after supplementation ended, the serum lutein concentration decreased; the MPOD remained elevated in both groups. CONCLUSIONS: The serum lutein concentrations and MPOD levels increased significantly with either free lutein or lutein esters, and no significant differences were found between the two. Both were considered useful as lutein supplements. PMID- 27273911 TI - A novel HLA-B allele, HLA-B*35:279, identified by sequencing-based typing in a Czech patient. AB - The identification of a novel HLA-B*35:279 allele in a Czech patient is described. This allele is identical to the B*35:03:01 variant except the G/A nucleotide exchange at position 652 of the HLA-B gene that corresponds to the amino acid substitution from valine to isoleucine in alpha 3 domain of the HLA-B antigen. PMID- 27273912 TI - Preferences for Disease-Related Education and Support Among Younger People With Hip or Knee Osteoarthritis. AB - OBJECTIVE: To explore the usefulness and accessibility of different delivery modes of disease-related education and support, as perceived by younger people with osteoarthritis (OA). METHODS: People ages 20-55 years with hip or knee OA were recruited from 3 major Australian public hospitals and the community (n = 147). Data were collected on use of disease-related education and support services, as well as perceived usefulness and accessibility of delivery modes including group-based programs, online resources, telephone helplines, mailed information, social media, and mobile applications (rated on visual analog scales from 1-10; higher scores indicate greater usefulness or accessibility). RESULTS: Very few participants had used social media (5%), group self-management programs (3%), or telephone helplines (2%) to obtain OA information. Mailed information packs and online education programs were considered the most useful (median usefulness scores 8.0 and 7.0, respectively) and accessible methods (median accessibility scores 10.0 and 9.0, respectively) for providing OA education and support. Social media was perceived as least useful (median usefulness score 2.0) and least accessible; 45% of participants considered it "not at all useful," while 35% reported it would be "very difficult" to access OA education and support by this means. Less educational attainment was associated with greater perceived difficulty in accessing online/electronic delivery modes, while people in paid work perceived easier access. CONCLUSION: These data highlight the value of mailed information and online education to younger people with OA and can be used to develop targeted resources for individuals of working age. Social media was not a highly valued source of disease-related education and support. PMID- 27273913 TI - In vivo metabolism study of (R)-bambuterol in humans using ultra high performance liquid chromatography with tandem mass spectrometry. AB - (R)-Bambuterol, a selective beta2-adrenoceptor agonist, has been approved as a new drug for the treatment of asthma and chronic obstructive pulmonary disease by the China Food and Drug Administration and is currently under phase I clinical trials. In this study, a combined method based on ultra high performance liquid chromatography with triple quadrupole mass spectrometry and ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was employed for the identification of the major metabolites of (R) bambuterol in human plasma and urine after an oral dose of 10 mg. The metabolites were separated by gradient elution program and different sample preparation methods were compared. Totally, 12 metabolites of (R)-bambuterol were identified, including four metabolites in plasma and all 12 metabolites in urine. Among these, four metabolites are reported for the first time. The possible metabolic pathways of (R)-bambuterol were subsequently proposed. The results indicated that (R)-bambuterol was metabolized via hydrolysis, demethylation, oxygenation, glucuronidation, and sulfation pathways in vivo. This study revealed that this combined method was accurate and sensitive to identify the possible metabolites and to better understand the metabolism of (R)-bambuterol in vivo. PMID- 27273914 TI - Statins and Risk of Rheumatoid Arthritis: A Nested Case-Control Study. AB - OBJECTIVE: Statins have antiinflammatory/immunomodulatory effects that may be useful in preventing rheumatoid arthritis (RA), but previous observational studies about the risk of RA with statin use yielded conflicting results. The aim of this study was to determine whether high-intensity statin treatment is associated with reduced risk of RA. METHODS: Using data from the UK Clinical Practice Research Datalink, we performed a nested case-control analysis in a population-based cohort of patients who began receiving statins between 1997 and 2009 and were followed up until a first diagnosis of RA, death, end of registration with the physician's practice, or end of January 2011. For each case of RA, 10 age-, sex-, and calendar year-matched controls were randomly selected from risk sets. We estimated the hazard ratio (HR) of incident RA in the highest quintile of duration-weighted average statin intensity compared to the lowest, using conditional logistic regression. Models were adjusted for smoking status, total cholesterol level, obesity, history of cardiovascular disease, coexistent autoimmune disease, hypothyroidism, and persistence with treatment. RESULTS: The cohort included 528,654 new users of statins, with 1,357 new cases of RA occurring during a mean follow-up of 3.3 years, for an incidence rate of 7.9 per 10,000 person-years. Cases were more likely to be smokers, to have other autoimmune diseases, and to have had lower total cholesterol levels at baseline. The incidence of RA was lower in the highest statin intensity quintile (adjusted HR 0.77 [95% confidence interval 0.63-0.95]) in comparison to the lowest quintile. CONCLUSION: In this large population-based study, high-intensity statin treatment was associated with a reduced risk of RA in comparison to low-intensity statin treatment. PMID- 27273915 TI - Excitation Energy Transfer in meta-Substituted Phenylacetylene Multibranched Chromophores. AB - A comprehensive investigation into the spectral properties and excitation energy transfer in di- or tribranched dithienyldiketopyrrolopyrrole (DPP) molecules with meta-substituted benzene as a central core (TADPP2-TT and TADPP3), by means of steady-state and transient measurements and quantum chemical calculations, is reported. Excitation in the meta-substituted chromophores is localized on one of the DPP units in the branching molecules owing to the disruption of conjugation by meta substitution for both TADPP2-TT and TADPP3. Weak electronic couplings result from the long distance between the DPP chromophores and the steric effects from the attached side chains on DPP. The attachment of the acetylene linker in each branch, which has a very low twisting barrier, could also play an important role in reducing the interaction between DPP chromophores. The dynamics of the excited states show that excitation energy transfer occurs on the picosecond scale, which is attributed to the incoherent hopping mechanism. PMID- 27273916 TI - The need for ethical and pedagogical frameworks for developing online media in anatomy education. PMID- 27273917 TI - Endophthalmitis after small-gauge vitrectomy: a retrospective case series from Sweden. AB - PURPOSE: To investigate the anatomical and functional outcomes of acute-onset endophthalmitis after small-gauge vitrectomy. METHODS: Retrospective case series of patients who underwent 23- or 25-gauge vitrectomy at four centres in Sweden between 2008 and 2012. Postvitrectomy endophthalmitis was identified through the search of the journal records of each institution, and the diagnosis was based on clinical criteria regardless of culture results. RESULTS: Twenty-four patients (24 eyes) were included. The incidence of endophthalmitis following small-gauge vitrectomy was 0.14%. Indications for small-gauge vitrectomy enclosed epiretinal membrane (n = 13), retinal detachment (n = 5) and others (n = 6). Surgical technique included 23- and 25-gauge vitrectomy (23:1). Four eyes had sutured sclerotomies, and two had postoperative hypotony <7 mmHg. Days to endophthalmitis presentation varied between 1 and 21 (mean 6 +/- 6). Treatment methods included the following: tap and antibiotic injection (n = 7), tap, antibiotic injection with subsequent vitrectomy (n = 2) and prompt vitrectomy with antibiotics (n = 15). Sixteen eyes (66.7%) were culture positive, whereas the other eight cases were culture negative. Anatomical results included evisceration (n = 1), phthisis (n = 1), and globe intact (n = 22). Presenting best corrected visual acuity (BCVA) were hand motion (n = 14), light perception (n = 7), counting fingers (n = 2), and no data (n = 1). Functionally 19 eyes (79%) had Snellen VA >=0.1; 11 eyes (46%) had VA >=0.5 Mean logMar BCVA preoperatively and at the last follow-up were 2.07 +/- 0.6 and 0.79 +/- 0.99, respectively. CONCLUSIONS: In spite of good anatomical and functional results, this study showed higher rate of endophthalmitis than the latest reports suggesting that small-gauge vitrectomy has reached the safety level of standard 20-gauge vitrectomy when infectious endophthalmitis is concerned. PMID- 27273918 TI - A DANGEROUS MUDDYING OF THE WATERS? THE 'SIGNIFICANT HARM' OF RE B AND G (CHILDREN) (CARE PROCEEDINGS)[2015] EWFC 3. AB - The academic debate rages on as to whether male circumcision really is in the best interests of the child or if it constitutes an abusive practice. This commentary discusses the recent case of Re B and G (children) (care proceedings) [2015] EWFC 3, delivered by the current President of the Family Division of the High court, Sir James Munby. Two key issues are raised by this judgment. First, that President Munby's obiter comments constitute an attack on the legally accepted act of male circumcision by suggesting a similar nature between the illegal act of female genital mutilation (FGM) and that of male circumcision as well as the suggestion that male circumcision can be classed as a significant harm. Second, that this case reflects the woefully unprepared condition of the UK medical profession in dealing with FGM. PMID- 27273919 TI - TRUST A v X AND OTHERS: THE GHOST OF NIELSEN RETURNS? AB - The case of Trust A v X and Others suggests that parents can authorise significant restrictions to be imposed on their disabled children. The court held that the parents of a D, a 15-year-old boy with autism and challenging behaviour, could consent to their son's placement in a locked psychiatric ward for over 15 months, whereas if such restrictions were placed on a child of that age without such disabilities, they would 'probably amount to ill treatment'. Focussing on two main areas of concern, it is argued that this decision is questionable and provides little assistance in determining whether parents can consent to their child's admission to hospital. First, the decision seems to be influenced by a misunderstanding of the basis on which the European Court of Human Rights (ECtHR) determines if a deprivation of liberty has arisen. Secondly, the court appears to have assumed that as D's parents were acting in his best interests, they were able to authorise extensive restrictions on their son, which is not the case. Such an approach renders disabled children's rights in this area almost non existent and far exceeds the parental powers envisaged by the ECtHR in Nielsen v Denmark (1988), which has been subject to widespread criticism for failing to uphold the rights of the child. PMID- 27273920 TI - European Court of Human Rights Rulings in Home Birth Set to Cause Trouble for the Future: A Review of Two Cases. AB - The safety of home birth is widely debated. The European Court of Human Rights (ECtHR) recently made two conflicting rulings on home birth, Ternovszky v Hungary and Dubska and Krejzova v the Czech Republic. In Ternovszky v Hungary, the ECtHR essentially forced Hungary to change existing legislation to allow home birth. In contrast, in Dubska and Krejzova v the Czech Republic, the Court found Czech Republic's stringent regulations against home birth acceptable. We describe these cases, the different evidence used and interpreted by the court and examine the ethical conflict between maternal autonomy and the rights of the newborn. PMID- 27273921 TI - Design, synthesis, and structure-activity relationship studies of novel pleuromutilin derivatives having a piperazine ring. AB - A series of novel pleuromutilin derivatives possessing piperazine moieties were synthesized under mild conditions. The in vitro antibacterial activities of these derivatives against Staphylococcus aureus and Escherichia coli were tested by the agar dilution method. Structure-activity relationship studies resulted in compounds 11b, 13b, and 14a with the most potent in vitro antibacterial activity among the series (minimal inhibitory concentration = 0.0625-0.125 MUg/mL). The binding of compounds 11b, 13b, and 14a to the E. coli ribosome was investigated by molecular modeling, and it was found that there is a reasonable correlation between the binding free energy and the antibacterial activity. PMID- 27273923 TI - Recurrent Episodes of Rhabdomyolysis after Seizures in a Patient with Glycogen Storage Disease Type V. PMID- 27273922 TI - Disability Progression in Multiple Sclerosis Is Affected by the Emergence of Comorbid Arterial Hypertension. AB - BACKGROUND AND PURPOSE: We assessed the prevalence and potential association of hypertension with multiple sclerosis (MS)-related disability progression. METHODS: This was a retrospective study of 2,813 patients who were followed for 20 years. We modeled the associations of several risk factors with the pattern of disability progression. The primary end point was the rate of disability progression. RESULTS: In total, 2,396 patients were available for analysis, of which 1,074 (44.8%) scored 4 (EDSS4) on the Expanded Disability Status Scale (EDSS), 717 (29.9%) scored 6 (EDSS6), and 261 (10.9%) scored 8 (EDSS8). The mean times to reach scores of 4, 6, and 8 were 123.5, 163.1, and 218.9 months, respectively. Hypertension was present in 207 (8.6%) patients during follow-up. Hypertension was associated with a higher probability of reaching each EDSS score compared to non-hypertensive patients: 62% vs. 43% for EDSS4 (p<0.01), 51% vs. 28% for EDSS6 (p<0.01), and 17% vs. 10% for EDSS8 (p<0.01). Nevertheless, hypertensive MS patients experienced longer intervals to reach each EDSS score: longer by 51.6, 38.9, and 62.7 months to EDSS4, EDSS6, and EDSS8, respectively (p<0.01) when compared to non-hypertensive MS patients reaching the same EDSS scores. CONCLUSIONS: Disability progression is more prevalent amongst hypertensive MS patients. However, they experience longer time intervals between the stages of disability progression. PMID- 27273924 TI - Tuberculomas Mimicking Posterior-Circulation Stroke. PMID- 27273925 TI - Estimating the Prevalence of Treated Epilepsy Using Administrative Health Data and Its Validity: ESSENCE Study. AB - BACKGROUND AND PURPOSE: Few of the epidemiologic studies of epilepsy have utilized well-validated nationwide databases. We estimated the nationwide prevalence of treated epilepsy based on a comprehensive medical payment database along with diagnostic validation. METHODS: We collected data on patients prescribed of antiepileptic drugs (AEDs) from the Health Insurance Review and Assessment service, which covers the entire population of Korea. To assess the diagnostic validity, a medical records survey was conducted involving 6,774 patients prescribed AEDs from 43 institutions based on regional clusters and referral levels across the country. The prevalence of treated epilepsy was estimated by projecting the diagnostic validity on the number of patients prescribed AEDs. RESULTS: The mean positive predictive value (PPV) for epilepsy was 0.810 for those prescribed AEDs with diagnostic codes that indicate epilepsy or seizure (Diagnosis-E), while it was 0.066 for those without Diagnosis-E. The PPV tended to decrease with age in both groups, with lower values seen in females. The prevalence was 3.84 per 1,000, and it was higher among males, children, and the elderly. CONCLUSIONS: The prevalence of epilepsy in Korea was comparable to that in other East Asian countries. The diagnostic validity of administrative health data varies depending on the method of case ascertainment, age, and sex. The prescriptions of AEDs even without relevant diagnostic codes should be considered as a tracer for epilepsy. PMID- 27273927 TI - Ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry and chemometric analysis of licorice based on the simultaneous determination of saponins and flavonoids. AB - Licorice is among the most popular herbal medicines and frequently used in traditional medicine, food products, and cosmetics. In China, only Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. and Glycyrrhiza glabra L. are officially used and are usually processed with honey prior to use. To maintain the quality of commercially available herbal products, a simple, rapid, and reliable ultra high performance liquid chromatography with triple quadrupole mass spectrometry was developed to investigate the major active constituents of commercially available licorice products. Nineteen components were accurately determined, including eight triterpenoid saponins, one triterpene, and ten flavonoids. Subsequently, multivariate statistical analysis methods were employed to further explore and interpret the experimental data. The results indicated that liquiritin apioside may be considered as a candidate index for the quality control of licorice as well as 18beta-glycyrrhizic acid and liquiritin. In addition, both 18beta-glycyrrhizic acid and licorice-saponin G2 can be used for discrimination between crude and honey-processed licorice. Furthermore, using 18beta-glycyrrhizic acid and liquiritin as markers, this work revealed that the quality of licorice products may have declined in recent years. This highlights the need for additional effort focused on good agricultural practice during the processing of licorice. In summary, this study provides a valuable reference for the quality assessment of licorice. PMID- 27273926 TI - "You Obviously Just Have to Put on a Brave Face": A Qualitative Study of the Experiences and Coping Styles of Men With Rheumatoid Arthritis. AB - OBJECTIVE: To explore the experiences, coping styles, and support preferences of male rheumatoid arthritis (RA) patients. METHODS: Six focus groups comprised 22 men with RA. Transcripts were analyzed using inductive thematic analysis. RESULTS: Three overarching themes describe the experiences, coping styles, and support preferences of men with RA. In "challenges to masculinity," the men described a "reduction in strength and abilities," which can lead to loss of independence, "challenges to masculine identity and role," and "loss of power and control." Coping by "getting through life with RA" meant dealing with RA by "just getting on with it," "information seeking," engaging in "destructive behaviors," and "withdrawing socially." Preferred "sources of support" tended not to include friends, as they were perceived to lack understanding or support. For acceptable support the men reported a preference for information-giving sessions rather than a discussion group, but there was no agreement on whether these should be mixed sex or men only, or who should run the sessions. CONCLUSION: Male patients reported a range of coping styles and support preferences to address their experiences of living with RA, many of which may not be shared with women. Further research is needed to investigate whether these findings exist in a larger sample and whether the support preferences of men with RA are broadly different from those of women with RA to decide whether there is a clinical need to design a service for the potentially different needs of men. PMID- 27273929 TI - Sulfur Confined in Sub-Nanometer-Sized 2 D Graphene Interlayers and Its Electrochemical Behavior in Lithium-Sulfur Batteries. AB - Microspace-confined sulfur molecules as cathodes for lithium-sulfur (Li-S) batteries have shown great significance in both scientific and technical aspects. A study of different microspace-confined sulfur will not only promote the advancement of Li-S batteries but also arouse a wide interest in sulfur chemistry and related applications. Herein, we choose two-dimensional (2D) graphene interlayer as host and construct 2D space-confined sulfur model systems by simple intercalation chemistry of graphite oxide. Two routes, including solvothermal method and interlamellar reaction approach, are developed, and sulfur can be easily intercalated into sub-nanometer-sized graphene interlayers, forming a graphene confined sulfur structure. The 2D space-confined sulfur can work well in a carbonate-based electrolyte and show similar electrochemical behaviors of small sulfur molecules, indicating the special molecular form of sulfur in graphene layers. The 2D space-confined sulfur concept will be helpful for further understanding the electrochemical character of confined sulfur molecules and designing a high-performance sulfur cathode. PMID- 27273928 TI - Brief Report: Management of Chronic Post-Chikungunya Rheumatic Disease: The Martinican Experience. AB - OBJECTIVE: To describe chronic chikungunya manifestations seen during the outbreak in the Caribbean from December 2013 to January 2015. METHODS: Patients were seen at our center, the only rheumatology department in Martinique Island, and were examined by a senior rheumatologist using a standard care report form. Chikungunya was diagnosed collectively based on consensus among all clinicians. The median time from onset of acute chikungunya to the first rheumatology consultation was calculated, severity was evaluated based on clinical scales and the degree of joint destruction, and each patient's treatment was recorded. RESULTS: For the 147 patients analyzed, the median time between onset of acute chikungunya and the first rheumatology consultation was 8 months. After review of each patient's medical record, 19 (12.9%) were diagnosed as having epidemic influenced chikungunya. Four distinct rheumatologic patterns were observed in the remaining patients (those with compatible history and positive serologic findings): 47 patients (32%) had reactivation of painful chronic mechanical manifestations, 9 patients (6.1%) had fibromyalgia, 45 patients (30.6%) met criteria for spondyloarthritis (as evaluated before the chikungunya virus infection in all patients) and experienced a flare, and 27 patients (18.4%), with no history of joint disease, developed de novo bilateral symmetric chronic inflammatory joint disease in response to chikungunya virus infection. For inflammatory arthritis, most patients were treated with methotrexate (up to 25 mg/week), with good response and tolerance. Thirteen patients were treated with conventional doses of anti-tumor necrosis factor agents, with good tolerance and efficacy as expected. CONCLUSION: The term "chronic chikungunya syndrome" covers multiple etiologies. Compliance with the French Society of Rheumatology recommendations, careful recording of patient histories, and serologic verification help prevent errors inherent to the epidemic context and ensure early therapeutic intervention for these patients. To avoid late initiation of treatment, patients should receive rheumatologic consultation as early as possible. PMID- 27273930 TI - Anisometropia of ocular refractive and biometric measures among 66- to 79-year old female twins. AB - PURPOSE: To examine the prevalence of anisometropia of spherical refraction (AnisoSR), astigmatism (AnisoAST) and spherical equivalent (AnisoSE) and their associations with spherical refraction (SR), refractive astigmatism (AST), spherical equivalent (SE) and interocular differences of ocular biometric parameters among elderly female twins. METHODS: Refraction of 117 monozygotic (MZ) and 116 dizygotic (DZ) female twin subjects aged 66-79 years was assessed with an auto-refractor (Topcon AT) and controlled by subjective refraction. Corneal refraction, anterior chamber depth and axial length were measured with a Zeiss IOL Master. Participants with eyes operated for cataract or glaucoma were excluded, but the grade of nuclear opacity was not recorded. The associations between the absolute values of AnisoSR, AnisoAST and AnisoSE with SR, AST, SE, corneal refractive power (CR), corneal astigmatism (CAST), anterior chamber depth (ACD) and axial length (AL) and with their interocular differences were calculated. When calculating the interdependencies of the differences, the real and absolute differences between the right and left eye were used. RESULTS: Means +/- standard deviations for AnisoSR, AnisoAST and AnisoSE were 0.67 +/- 0.92 D, 0.42 +/- 0.41 D and 0.65 +/- 0.71 D, respectively. AnisoSR, AnisoAST and AnisoSE >1.0 D were present in 14.7%, 4.2% and 17.7% of cases, respectively. Anisometropia of spherical refraction (AnisoSR), AnisoAST and AnisoSE were higher the more negative the values of SR or SE. Hyperopic ametropia did not increase these anisometropia values. The correlations of AnisoSR and AnisoSE with the absolute values of interocular differences in CR and AL were non-significant. Using the real values of the interocular differences, the respective correlations were significant. The correlation between the real interocular differences in CR and AL was negative (r = -0.258, p < 0.001). Thus, the combined effect of the real interocular differences in CR and AL was a decrease in AnisoSR and AnisoSE (emmetropization). CONCLUSION: Higher AnisoSR and AnisoSE were associated with more myopic refraction and longer AL. Higher AnisoAST was associated with more negative SR and higher AST and CAST. The negative correlation between real interocular differences in CR and AL indicated their influence of emmetropization in AnisoSR and AnisoSE. PMID- 27273932 TI - The Global Burden of Cardiovascular Disease. PMID- 27273931 TI - Persistence of megalencephaly in a subgroup of young boys with autism spectrum disorder. AB - A recurring finding in autism spectrum disorder research is that head and brain growth is disproportionate to body growth in early childhood. Nordahl et al. (2011) demonstrated that this occurs in approximately 15% of boys with autism. While the literature suggests that brain growth normalizes at older ages, this has never been evaluated in a longitudinal study. The current study evaluated head circumference and total cerebral volume in 129 male children with autism and 49 age-matched, typically developing controls. We determined whether 3-year-old boys with brain size disproportionate to height (which we call disproportionate megalencephaly) demonstrated an abnormal trajectory of head growth from birth and whether they maintained an enlarged brain at 5 years of age. Findings were based on longitudinal, structural MRI data collected around 3, 4, and 5 years of age and head circumference data from medical records. At 3 years of age, 19 boys with autism had enlarged brains while 110 had brain sizes in the normal range. Boys with disproportionate megalencephaly had greater total cerebral, gray matter, and white matter volumes from 3-5 years compared to boys with autism and normal sized brains and typically developing boys, but no differences in body size. While head circumference did not differ between groups at birth, it was significantly greater in the disproportionate megalencephaly group by around 2 years. These data suggest that there is a subgroup of boys with autism who have brains disproportionate to body size and that this continues until at least 5 years of age. Autism Res 2016, 9: 1169-1182. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27273933 TI - Heroes in the Field. PMID- 27273934 TI - Dietary Fat Intake and Radiographic Progression of Knee Osteoarthritis: Data From the Osteoarthritis Initiative. AB - OBJECTIVE: Few studies have investigated the role of dietary factors on knee osteoarthritis (OA) progression. We examined the prospective association of dietary fat intake with radiographic progression of knee OA. METHODS: In the Osteoarthritis Initiative, 2,092 participants with radiographic knee OA and having baseline dietary data were followed at yearly intervals up to 48 months. Dietary intakes of fatty acids were assessed with the Block Brief Food Frequency Questionnaire. To evaluate radiographic progression of knee OA, we used quantitative joint space width (JSW) between the medial femur and tibia of the knee based on fixed-flexion posteroanterior radiographs. Linear mixed models for repeated measures were used to test the association between dietary fat and JSW loss over time. RESULTS: We observed significant positive relationships of total fat and saturated fatty acids (SFA) intakes with JSW loss. With increasing quartiles of total fat intake, JSW decreases over 48 months were 0.26 mm, 0.27 mm, 0.31 mm and 0.35 mm, respectively (P = 0.02 for trend). Similar association was observed between SFA intake and JSW loss. In contrast, higher intakes of mono (MUFA) and polyunsaturated fatty acids (PUFA), and higher ratio of PUFA to SFA were associated with a reduced JSW loss. CONCLUSION: High intakes of total fat and SFA may be associated with increased structural knee OA progression, while MUFA and PUFA may reduce radiographic progression. Replication of these novel findings in other prospective studies is needed to confirm if reduction in SFA intake and increase in unsaturated fat intake lead to delayed knee OA progression. PMID- 27273935 TI - Effect of music therapy on pain behaviors in rats with bone cancer pain. AB - PURPOSE: To investigate the effects of music therapy on the pain behaviors and survival of rats with bone cancer pain and analyze the mediating mechanism of mitogen activated protein kinase (MAPK) signal transduction pathway. METHODS: Male Wistar rats aged 5-8 weeks and weighing 160-200 g were collected. The rat models of colorectal cancer bone cancer pain was successfully established. Animals were divided into experimental and control group, each with 10 rats. The animals in the observation group were given Mozart K448 sonata, sound intensity of 60 db, played the sonata once every 1 hr in the daytime, stopped playing during the night, and this cycle was kept for 2 weeks. On the other hand, rats in the control group were kept under the same environment without music. RESULTS: Animals in the experimental group consumed more feed and gained significant weight in comparison to the control group. The tumor volume of the experimental group was significantly smaller than that of the control group (p<0.05). After 1 2 weeks of treatment, spontaneous foot withdrawal reflection caused by pain in the experimental group was significantly lower than that in the control group, heat pain threshold and free walking pain scoring in the experimental group were also significantly higher as compared with the control group (p<0.05). The expression of p38a and p38beta in animals' spinal cord and dorsal root ganglion was significantly lower in the experimental group than in the control group (p< 0.05). CONCLUSION: Music therapy may improve the pain behaviors in rats with bone cancer pain, which might be related with low expression of p38a and p38beta in the MAPK signal transduction pathway. PMID- 27273936 TI - Is there a current change of maintenance treatment in ovarian cancer? An updated review of the literature. AB - Maintenance therapy in ovarian cancer has been introduced and evaluated in many large randomized trials; however, its efficacy is still unclear and includes concerns for both short-term and longer-term side effects. Thus far, some therapies that have been studied in this setting showed a delay in tumor progression but unfortunately no improvement in overall survival has been noticed. The introduction of new chemotherapeutic agents redirected research efforts. Assessing benefits of prolonged therapy and its impact in terms of toxicity is considerably important for the decision to administer such treatments. The purpose of this article was to provide an update on the randomized trials and review the role of maintenance therapy in the treatment of ovarian cancer. PMID- 27273937 TI - Epigenetic mechanisms in endometrial cancer. AB - Purpose: Endometrial cancer is a very common type of cancer in females worldwide. Advances in diagnosis and treatment have not decreased the incidence of endometrial cancer. Lately, research has been focused on revealing the molecular and genetic characteristics of endometrial cancer in order to provide new insights in the biology of this entity, leading hopefully to innovating therapies. Research has revealed that epigenetic modifications govern endometrial carcinogenesis. In this review, the epigenetic mechanisms that are involved in endometrial cancer as well as the differences between the different types of endometrial cancer are discussed. The review also refers to the putative therapeutic benefits that hopefully can arise. PMID- 27273938 TI - Recent advances in the management of hepatocellular carcinoma. AB - Purpose: The fifth most common cancer of the gastrointestinal system is liver cancer. It is also one of the most common cancers worldwide. The available treatment options include surgery, percutaneous ablation, and liver transplantation. Some of the latest modalities for the management of hepatocellular carcinoma (HCC) are radiofrequency ablation, trans-arterial chemoembolization, radioembolization and systemic targeted agents like sorafenib. The process of choice of a particular treatment modality in HCC depends on the tumor stage, patient performance status and liver function reserve. In the recent past with progress in research, the short-term survival of HCC has improved but recurrent disease remains a fundamental problem as the pathogenesis of HCC is a multistep and complex process. The present review is focused on recent advances in the management of HCC. This review will also provide an insight on the upcoming latest modalities including the emerging role of hepatoma-derived growth factor (HDGF) overexpression in liver fibrosis and carcinogenesis. PMID- 27273939 TI - Clinical significance of epithelial-mesenchymal transition and cancer stem cells. AB - Purpose: Spread of cancer cells from the organ of the origin of them to another location, namely metastasis, is one of the most important factors that complicate the treatment of cancer. Therefore, research for the treatment of metastatic disease is gaining importance, especially for advanced cancers. This research focuses on the mechanisms that facilitate the metastatic tendency of cancer cells. Therefore, epithelial-mesenchymal transition (EMT) mechanism that helps the cells become metastatic and cancer stem cells (CSCs) present in the heterogeneous tumor mass are in the center of these researches. PMID- 27273940 TI - Cervical cancer: screening, diagnosis and staging. AB - Purpose: Despite the widespread screening programs, cervical cancer remains the third most common cancer in developing countries. Based on the implementation of cervical screening programs with the referred adoption of improved screening methods in cervical cytology with the knowledge of the important role of the human papilloma virus (HPV) it's incidence is decreased in the developed world. Even if cervical HPV infection is incredibly common, cervical cancer is relatively rare. Depending on the rarity of invasive disease and the improvement of detection of pre-cancerous lesions due to the participation in screening programs, the goal of screening is to detect the cervical lesions early in order to be treated before cancer is developed. In populations with many preventive screening programs, a decrease in cervical cancer mortality of 50-75% is mentioned over the past 50 years. The preventive examination of vagina and cervix smear, Pap test, and the HPV DNA test are remarkable diagnostic tools according to the American Cancer Association guidelines, in the investigation of asymptomatic women and in the follow up of women after the treatment of pre invasive cervical cancer. The treatment of cervical cancer is based on the FIGO 2009 cervical cancer staging. PMID- 27273941 TI - A randomized study comparing the effectiveness of microwave ablation radioimmunotherapy and postoperative adjuvant chemoradiation in the treatment of non-small cell lung cancer. AB - PURPOSE: To evaluate the differences in the outcomes of patients with stage II and IIIa non-small cell lung cancer (NSCLC) treated with either 131I-labeled mouse/human chimeric monoclonal antibody against intracellular DNA exposed in necrotic and degenerating regions of tumors (131I-chTNT-mediated radioimmunotherapy) combined with percutaneous microwave coagulation therapy (PMCT) guided by computed tomography (CT) or with postoperative adjuvant chemoradiation. METHODS: Ninety-six patients with stage II and IIIa NSCLC were randomized into two groups. Group A included 49 patients who were treated with chemotherapy with docetaxel and cisplatin and three-dimensional conformal radiotherapy 3-4 weeks after surgery. Group B included 47 patients treated with 131I-chTNT and PMCT sequentially, with follow-up chemotherapy. RESULTS: The survival rates of patients in group A for the first and second years were 79.59% and 48.98%, respectively. The median survival was 23.0 months. Survival rates at 1 and 2 years for group B were 82.98% and 53.19%, respectively and the median survival was 29.1 months. The survival rate of group B patients for the first and second years was better compared with group A, and the difference in median survival between the groups was statistically significant (p<0.05). However, median survival and the incidence of adverse events were not significantly different between the two groups. CONCLUSIONS: 131I-chTNT radioimmunotherapy with PMCT has a complementary effect in NSCLC, which can effectively improve therapeutic ratio and survival of patients effectively and has the same effect as that of post-operative adjuvant chemoradiation. PMID- 27273942 TI - Comparison of the efficacy of radiotherapy between postoperative mediastinal lymph node recurrence and stage III disease in non-small cell lung cancer patients. AB - PURPOSE: It is unknown if local treatment is equally effective in non-small cell lung cancer (NSCLC) patients with postoperative mediastinal lymph node recurrence or primary stage III disease. The purpose of this study was to investigate the effectiveness of radiotherapy, with or without chemotherapy, in patients with postoperative mediastinal lymph node recurrence. METHODS: Patient characteristics, treatment response and survival were compared between NSCLC patients with mediastinal lymph node metastases treated between 2002-2009 by radiotherapy alone or by chemoradiotherapy (group A, N=33) and those with primary stage III disease (group B, N = 157). RESULTS: Men accounted for 60.6% of group A and 78.9% of group B (p=0.04 patients). ECOG performance status 0 was detected in 78.7% of group A and 57.3% of group B (p=0.02). The response rates in groups A and B were 66.6 and 72.3%, respectively (p=0.64). Progression-free survival (PFS) was similar between groups A and B (median 15.0 vs 11.0 months; hazard ratio [HR] 0.78; 95% CI 0.51-1.20; p=0.26). However, overall survival (OS) was better in group A than in group B (median 67.0 vs 39.0 months; HR 0.56; 95% CI 0.29-0.97; p=0.03). Postoperative PFS (median 12.5 vs 19.0 months; HR 1.50; 95% CI 0.64 3.49; p=0.34) and OS (median, 67.0 vs 60.0 months; HR 1.22; 95% CI 0.36-4.14; p=0.74) were similar between the group A treatments (radiotherapy and chemoradiotherapy, respectively). CONCLUSION: Postoperative mediastinal lymph node recurrent NSCLC demonstrated distinctive features including better OS compared to patients with primary stage III disease, despite similar response rates and PFS. PMID- 27273943 TI - Prognostic significance of overexpressed matrix metalloproteinase-2, mouse-double minute: 2 homolog and epidermal growth factor receptor in non-small cell lung cancer. AB - PURPOSE: To evaluate the rate of overexpression of matrix metalloproteinase-2 (MMP2), mouse double minute 2 homolog (MDM2) and epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), and evaluate their correlation with clinicopathological parameters and prognosis. METHODS: This was a prospective cohort study conducted from 2003 to 2008 among 184 NSCLC patients who underwent tumor resection. Each patient's clinical history and tumor characteristics were obtained from histopathology reports and medical records. EGFR, MDM2 and MMP2 expression were assessed by immunohistochemical (IHC) staining of the tissue specimens. RESULTS: MDM2 overexpression was observed in 70 (38%) of the patients studied, and was significantly higher in younger patients (p=0.01). Only 46 (25%) of patients had overexpression of MMP2. EGFR positive staining occurred in 105 (57%percnt;) of the evaluated tumor specimens and was more frequent in specimens with squamous cell carcinoma (p<0.001), the elderly (p<0.001), and in smokers (p<0.001). Independent risk factors for mortality were older age (adjusted odds ratio/aOR 1.3=), being a smoker (aOR 10), having stage II disease (aOR 10.8) or stage III/IV disease (aOR 28.3), expression of EGFR (aOR 5.9) and MMP2 (aOR 4.1). However, the expression of MDM2 independently predicted a reduced risk of death (aOR 0.3). CONCLUSION: Overexpression of MMP2 and EGFR were independent risk factors for mortality in NSCLC patients, while overexpression of MDM2 independently predicted a reduced risk of death. PMID- 27273944 TI - Results of third-generation epirubicin/cisplatin/xeloda adjuvant chemotherapy in patients with radically resected gastric cancer. AB - PURPOSE: The purpose of this study was to evaluate the efficacy and toxicity of a third-generation chemotherapy regimen in the adjuvant setting to radically operated patients with gastric cancer. This proposed new adjuvant regimen was also compared with a consecutive retrospective cohort of patients treated with the classic McDonald regimen. METHODS: Starting in 2006, a non-randomized prospective phase II study was conducted at the Institute of Oncology of Cluj Napoca on 40 patients with stage IB-IV radically resected gastric adenocarcinoma. These patients were administered a chemotherapy regimen already considered to be standard treatment in the metastatic setting: ECX (epirubicin, cisplatin, xeloda) and were compared to a retrospective control group consisting of 54 patients, treated between 2001 and 2006 according to McDonald's trial. RESULTS: In a previous paper, we reported toxicities and the possible predictive factors for these toxicities; in the present article, we report on the results concerning predictive factors on overall survival (OS) and disease free survival (DFS). The proposed ECX treatment was not less effective than the standard suggested by McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage was an independent prognostic factor for OS and DFS. N ratio >70% was an independent predictive factor for OS and locoregional disease control. The resection margins were independent prognostic factors for OS and DFS. CONCLUSION: The proposed treatment is not less effective compared with the McDonald's trial. Age was an independent prognostic factor in multivariate analysis. N3 stage represented an independent prognostic factor and N ratio >70% was a predictive factor for OS and DFS. The resection margins were proven to be independent prognostic factors for OS and DFS. PMID- 27273945 TI - Clinical and pathological characteristics and their effect on survival in elderly patients with gastrointestinal stromal tumors. AB - PURPOSE: Gastrointestinal stromal tumors (GISTs) are common tumors of the gastrointestinal tract. Their most frequent location is the stomach. Although the clinical and pathological characteristics of the disease are well-known, the clinical and pathological characteristics and the response to treatment are not clear in elderly patients. The purpose of this study was to evaluate the characteristics of GISTs in elderly patients with an aim at improving the therapeutic methodology and survival. METHODS: In this study, clinicopathological characteristics, evaluation of treatments administered and survival analyses were performed in patients aged 65 years or above, whose data were registered via a web-based patient records system following admission to three centers. RESULTS: A total of 85 patients aged 65 years or above were included in the study. According to the risk classification, 24 (28.2%) were in the low risk group, 20 (23.5%) in the moderate risk group, and 41 (48.3%) in high risk group, while no patient was in the very low risk group. At baseline, 70% of the patients had localized disease and 30% metastatic disease. The tumor was located in the stomach in the majority of the patients (45.6%). The tumor size most commonly seen was 5-10 cm (N=31; 36.4%). Of the 85 patients 23 (27%) were treated with imatinib 400 mg/d. Eight patients (9.4%) with metastatic disease switched from imatinib to sunitinib. At a median follow-up of 76 months (range 1-323), median overall survival (OS) was 72 months, without significant difference between elderly and younger patients. CONCLUSION: Clinicopathological characteristics and their prognostic impact on the disease course of elderly GIST patients should be elucidated in depth. Since age didn't show prognostic importance, other parameters should be used as prognostic/predictive factors in the tyrosine kinase inhibitors era in order to obtain improved therapeutic results. PMID- 27273946 TI - Identification of disrupted pathways in ulcerative colitis-related colorectal carcinoma by systematic tracking the dysregulated modules. AB - PURPOSE: The aim of this study was to identify the altered biological pathways associated with ulcerative colitis (UC)-related colorectal carcinoma (CRC) by systematic tracking the dysregulated modules from re-weighted protein- protein interaction (PPI) networks based on the expression profiles from normal, UC and various stages of CRC. METHODS: We firstly recruited the UC- and CRC-related microarray data from ArrayExpress database, and obtained 8 expression profiles which contained 5 conditions (normal, UC, early stage CRC, stage II CRC and stage III CRC). Then, the PPI networks of normal and different disease stages were constructed and re-weighted using Pearson correlation coefficient (PCC). Next, the condition-specific modules were extracted from 5 PPI networks via clique merging algorithm, and altered modules were captured on the basis of module correlation density (MCD). Subsequently, the gene compositions of altered modules and gene differential expressions in different disease stages were identified to screen the dysregulated genes. Finally, pathways enrichment analyses for the genes in altered modules and differentially expressed genes (DEGs) were implemented. RESULTS: The extensive changes of gene correlations existed in 5 condition-specific PPI networks, which made different MCDs among different disease stages. The same number of modules (N=1952) were explored in 5 PPI networks. By comparing with normal condition, there were 463, 791, 1060 and 345 altered modules in UC, early stage CRC, stage II and III CRC, respectively. Overall, 77, 110, 170 and 110 common genes were identified between genes of altered modules and DEGs in UC, early stage CRC, stage II CRC and stage III CRC, respectively. Functional enrichment analyses indicated that cell cycle and oocyte meiosis were the common and most significant pathways in colonic diseases. CONCLUSIONS: Tracking the altered modules from PPI networks is useful to uncover disrupted pathways in colonic diseases. Cell cycle and oocyte meiosis might be associated with the pathophysiological background of colonic diseases. PMID- 27273947 TI - Efficacy and safety of eribulin monotherapy in patients with heavily pretreated metastatic breast cancer. AB - PURPOSE: Eribulin is a non-taxane microtubule inhibitor, which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated MBC patients. METHODS: In this single center trial, a total of 66 MBC patients who received eribulin monotherapy in Hacettepe University Cancer Institute between 2013 and 2015 were retrospectively analyzed. Kaplan-Meier survival analysis was carried out for progression free survival (PFS) and for overall survival (OS). Two-sided p values <0.05 were considered as statistically significant. RESULTS: Sixty-six patients who received at least one cycle of eribulin were registered. Most patients were heavily pretreated with a median of 4 (range 2-7) previous chemotherapy lines prior to eribulin. Median patient age was 50 years (range 28-67). Most patients were treated with eribulin at 4th or 5th line (33.3 and 27.3%, respectively). Brain metastases were present in 19 (28.8%) patients at the time of initial eribulin administration. Median PFS was 5 (95% CI 4.1-5.8) and median OS was 8 (95% CI 6 9.9) months. Fifteen patients (22.7%) responded to treatment with partial remission (PR) and 36 (54%) had stable disease (SD). No hypersensitivity reactions and no toxic deaths were observed. Three (5%) patients experienced grade 4 neurotoxicity. Fourteen (21.5%) patients developed grade 3-4 neutropenia. CONCLUSION: Eribulin monotherapy is an effective and safe regimen for MBC patients. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease in its intravenous administration make this agent a preferable option for both physicians and patients. PMID- 27273948 TI - The role of p95HER2 in trastuzumab resistance in breast cancer. AB - PURPOSE: Trastuzumab, the HER2 oncogene targeting drug, shows remarkable clinical efficacy in HER2-amplified breast cancer patients. Despite of robust activity, some of the patients with HER2-positive breast cancers do not get the benefit due to trastuzumab resistance. Overexpression of p95HER2 is one of the molecular mechanisms of trastuzumab resistance. The purpose of this study was to investigate whether p95HER2 overexpressing breast cancers were resistant to trastuzumab. METHODS: p95HER2 (truncated HER2) and HER2 were determined by real time polymerase chain reaction (RT-PCR) analysis. HER2 protein expression and HER2 gene amplification were also determined by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). Archival material from 80 formalin fixed paraffin-embedded (FFPE) breast cancer tumor tissues was used for the study. None of the cases had metastases at the initial diagnosis. HER2-positive cases were treated with trastuzumab with/without chemotherapy. RESULTS: Of 80 breast cancer cases 39 (48.7%) were HER2-positive and had trastuzumab treatment. Of these 39 cases 11 (28.2%) were trastuzumab-resistant and 28 (71.8%) were not, 17 (43.6%) were recurrent cases and 22 (56.4%) were not. Three patients died during follow-up. p95HER2 mean ratio was 11.01+/-19.73 in 11 cases which were trastuzumab-resistant, while p95HER2 mean ratio was 1.99+/-1.37 in 28 cases without trastuzumab resistance. If p95HER2 ratio was low, there was no trastuzumab resistance. However, when p95HER2 ratio was high, there was trastuzumab resistance (p=0.210, Mann-Whitney U test). CONCLUSION: p95HER2 was correlated with trastuzumab resistance, but it was not an independent factor of trastuzumab resistance. We claim that p95HER2 is sensitive but not specific for the prediction of trastuzumab resistance. PMID- 27273949 TI - Personalized discovery of altered pathways in clear cell renal cell carcinoma using accumulated normal sample data. AB - PURPOSE: To identify altered pathways in an individual with clear cell renal cell carcinoma (ccRCC) using accumulated normal sample data. METHODS: Gene expression data of E-GEOD-40435 was downloaded from the ArrayExpress database. Gene-level statistics of genes in tumor and normal samples were computed. Then, the Average Z method was applied to calculate the individual pathway aberrance score (iPAS). Subsequently, the significantly altered pathways in a ccRCC sample were identified using T-test based on the pathway statistics values of normal and ccRCC samples. Moreover, the identified altered pathways were verified through two methods: one was assessing classification capability for microarray data samples, and the other was computing the changed percentage of each pathway in ccRCC samples. RESULTS: Based on the threshold, 886 altered pathways were identified in all samples. The most significant pathways were potassium transport channels, proton-coupled monocarboxylate transport, beta oxidation of octanoyl CoA to hexanoyl-CoA, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. Additionally, iPAS separated ccRCC from normal controls with an accuracy of 0.980. Moreover, a total of 5 significant pathways with change in 100% ccRCC samples were extracted including proton-coupled monocarboxylate transport, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. CONCLUSIONS: iPAS is useful to predict marker pathways for ccRCC with a high accuracy. Pathways of proton-coupled monocarboxylate transport, and antigen presentation: folding, assembly and peptide loading of class I MHC might play crucial roles in ccRCC progression. PMID- 27273950 TI - Effectiveness of allogeneic CD3AK cells on transplanted human renal cell cancer in mice with severe combined immune deficiency. AB - PURPOSE: To assess the activity of allogeneic anti-CD3 antibody induced activated killer (CD3AK) cells on transplanted human renal cell cancer (RCC) in mice with severe combined immune deficiency (SCID), thus to provide theoretical and experimental support for clinical application of allogeneic CD3AK cells in the treatment of RCC. METHODS: A culture system which can massively increase allogeneic CD3AK cells was constructed. CCK-8 method was used to detect lethal effect of allogeneic CD3AK cells on human OS-RC-2 renal cancer cell line. Then, tumor-bearing mice models were constructed. SCID mice were randomly divided into four groups: group A (caudal vein was injected with allogeneic CD3AK cells before tumor bearing), group B (the control group of group A: caudal vein was injected with PBS before tumor bearing), group C (caudal vein was injected with allogeneic CD3AK cells after tumor bearing) and group D (the control group of group C: caudal vein was injected with PBS after tumor bearing), and spleen parameters were calculated to observe any inhibitory effect of allogeneic CD3AK cells on the growth of renal cancer cells, as well as their effect on the immune system of mice. RESULTS: Compared with the control groups B and D, spleen parameters of groups A and C increased significantly (p<0.05); compared with group C, spleen parameters of group A showed no obvious difference (p>0.05); compared with the control groups B and D, tumor weight of groups A and C decreased significantly and tumors grew slowly (p<0.05); the weight of mice in all groups increased while the weight of mice in the experimental groups increased less than the weight of mice in the control groups (p<0.05); compared with group C, tumor weight of group A reduced and grew slowly (p<0.05). Immunohistochemistry revealed that CD3+ cells showed positive expression in tumor tissues of mice in group C, while no positive expression was found in tumor tissues of mice in other groups. CONCLUSION: Allogeneic CD3AK cells exerted lethal effect on OS-RC-2 cell line and significant inhibitory activity on the growth of transplanted cancer in mice with SCID. Also CD3AK cells expressed certain preventive effect on the development of implanted cancer in SCID mice; allogeneic CD3AK cells possessed antitumor activity and could enhance the immunologic functions of SCID mice with human renal cell bearing cancer. PMID- 27273951 TI - Analysis of short and long term therapeutic effects of radiofrequency hyperthermia combined with conformal radiotherapy in hepatocellular carcinoma. AB - PURPOSE: To investigate the immediate and long term therapeutic effects of radiofrequency hyperthermia combined with conformal radiotherapy in patients with hepatocellular carcinoma (HCC). METHODS: Data was collected from 80 patients with HCC. All of the patients had confirmed primary HCC according to their clinical symptoms, imaging examinations, biochemical examinations and pathology. Patients were randomly divided into control group and experimental group, with 40 cases each. Patients in the control group were treated with conformal radiotherapy while patients in the experimental group were treated with conformal radiotherapy combined radiofrequency hyperthermia. Finally, the short and long term outcomes were compared between the groups. RESULTS: The levels of bilirubin, ALT and prothrombin time (PT) in both groups reduced after treatment and the reduction was more pronounced in the experimental group. In both groups of patients albumin was elevated and in the experimental group this elevation was significantly more pronounced (p<0.05). The total efficiency for patients in the experimental group was significantly higher than that in the control group (p<0.05). Follow-up results showed that 6-month and 1-year recurrence and mortality rates were significantly lower in the experimental group compared with the control group (p<0.05). CONCLUSION: Radiofrequency hyperthermia combined conformal radiotherapy is remarkably effective in treating patients with HCC, which could effectively reduce the damages of radiotherapy to the liver, enhance the patient' s tolerability and improve the patients' short and long term survival. PMID- 27273952 TI - Microwave versus saline-linked radiofrequency (Aquamantys) assisted liver resection in a porcine liver resection model. A safety and feasibility pilot study. AB - PURPOSE: The aim of this study was to compare the feasibility, efficacy and safety of microwave ablation and saline-linked radiofrequency (Aquamantys) in liver resection. METHODS: Sixteen domestic pigs (8 per group) underwent thermoablations. Group A consisted of 8 pigs in which microwave left lateral liver resection was performed. Group B consisted of 8 pigs which underwent left lateral liver resection by the Aquamantys system. After 28 days of close follow up, the animals were sacrificed in order to study the macroscopic and microscopic findings of each intervention on the liver edge. RESULTS: An average of 47.13 min was enough for the entire operation to take place using Aquamantys, whereas an average of 59.13 min was needed in the microwave liver resection group. Mean blood loss was 40 ml (range 5-85) with Aquamantys whereas mean blood loss was 72.37 ml (range 42-100) using microwave. Postoperative complications rates were extremely low in both groups. There was no intra- or postoperative mortality. CONCLUSIONS: Our study demonstrated that left lateral liver resection using Aquamantys system is technically feasible in the porcine model and proved to be highly effective and a safer hemostatic method compared to microwave ablation. PMID- 27273953 TI - The management of patients with esophageal cancer and coronary artery stenosis undergoing radiotherapy or concurrent chemoradiotherapy: a single-center experience. AB - PURPOSE: The incidence of esophageal cancer (EC) patients with coronary artery stenosis presents particular challenges. The aim of this retrospective study was to evaluate the efficiency of management on patients with both diseases treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: Fifty-three patients with both EC and coronary artery stenosis from June 2009 to August 2012 were retrospectively analyzed. The patients received RT or CCRT with coronary artery stenosis management. Cardiac treatments often prescribed included aspirin, beta-blockers, statins etc. The adverse effects, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Most of the patients were 40-70 years old. There were 25 patients in the CCRT group and 28 patients in the RT group. The complete response (CR) rate was higher in the patients in the CCRT group than in those in the RT group (48.0 vs 21.4%; p=0.041). The median PFS was 15.9 months in the CCRT group and 11.6 months in the RT group (p=0.025). OS was 22.4 months in the CCRT group and 15.8 months in the RT group (p=0.013). Though adverse effects were less in the RT group, no significance differences in grade 3-4 toxicity were observed. CONCLUSION: With the appropriate of coronary artery stenosis management, RT and CCRT were both tolerable and effective in EC patients with coronary artery stenosis. PMID- 27273954 TI - Survival following video-assisted thoracoscopic versus open esophagectomy for esophageal carcinoma. AB - PURPOSE: This study aimed to compare the overall and disease-free survival of patients who underwent video-assisted thoracoscopic esophagectomy (VATE) or open esophagectomy for esophageal carcinoma. METHODS: Patients who underwent radical esophagectomy via VATE (VATE group, N=89) for esophageal carcinoma between January 2008 and December 2012 were retrospectively enrolled in this study. Patients subjected to open radical esophagectomy (open group) were retrospectively included at a ratio of 1:1, matching the VATE group in sex, age, clinical TNM stage, location of the primary tumor and ASA (American Society of Anesthesiologists) score. RESULTS: All the video-assisted thoracoscopic procedures were successfully completed, without conversion to open procedure. The age, gender, clinical TNM stage, location of the primary tumor and ASA score were similar in the two groups. VATE group was associated with significantly less blood loss and shorter hospital stay. The operative morbidity and mortality were similar between the two groups. The quality of the specimens in terms of resection margin and the number of lymph nodes examined were not inferior in the VATE group. With the median follow-up of 52 months, the 5-year overall survival and disease-free survival were similar between the two groups. The operative approach was not an independent prognostic factor in the overall and disease-free survival in univariate and multivariate analysis. CONCLUSIONS: VATE for esophageal carcinoma is associated with more favorable short-term outcomes and comparable long-term prognosis when compared with open esophagectomy. PMID- 27273955 TI - MicroRNA-146b acts as a potential tumor suppressor in human prostate cancer. AB - PURPOSE: MicroRNAs (miRs) act as either tumor suppressors or oncogenes and are frequently deregulated in cancers. Although downregulation of miR-146b has been reported in various cancers, its role in prostate cancer is totally unknown. METHODS: The miR-146b expression in 18 human prostate cancer lines with case matched adjacent normal tissues was measured by quantitative RT-PCR. Furthermore, the expression levels of miR-146b in normal prostate and prostate cancer cell lines were assessed. Cell proliferation, apoptosis, migration and invasion assays were performed in overexpressing or knockdown miR-146b cells. RESULTS: miR-146b expression was significantly reduced in all prostate tumor tissues. Furthermore, miR-146b was significantly decreased in prostate cancer cells as compared to normal prostate cells. Loss-of-function and gain-of-function showed that miR-146b induced apoptosis and suppressed cell proliferation, migration and invasion of the prostate cancer cell lines. CONCLUSION: Our results demonstrated that miR 146b expression is downregulated in prostate tumor tissues and is a potential tumor suppressor miR, suggesting that miR-146b might be a potential clinical marker and therapeutic target for prevention and treatment of prostate cancer. PMID- 27273956 TI - Correlation of p210 BCR-ABL transcript variants with clinical, parameters and disease outcome in 45 chronic myeloid leukemia patients. AB - PURPOSE: The aim of this study was to search the BCR/ABL 1 fusion gene in 45 chronic myeloid leukemia (CML) Syrian patients using nested reverse transcription polymerase chain reaction (RT-PCR) and compare our results with those of conventional cytogenetics and molecular cytogenetics methods. METHODS: 45 bone marrow or peripheral blood samples from untreated CML patients in chronic phase (CP) were obtained at diagnosis, and analyzed by nested RT-PCR, conventional cytogenetics and molecular cyto-genetics methods. RESULTS: 45 patients examined were positive for some type of BCR/ABL1 fusion gene rearrangement. Out of 45 studied CML patients, 23 (51.1%) expressed b3a2 fusion transcript, 21 (46.7%) b2a2 transcript, and 1 (2.2%) a rare b2a3 transcript. No patient co-expressed both b3a2/b2a2 types. CONCLUSIONS: The distribution BCR-ABL1 transcript types found in Syria were similar to that of Indian Far-Eastern, African or European populations and the M-BCR rearrangement types were not dependent on white blood count (WBC), platelet count, hemoglobin level or gender of the patients. Overall, we could show that patients with b3a2 rearrangements were younger than patients with b2a2 transcripts, thus our young patients may have a worse prognosis. PMID- 27273957 TI - E-cadherin/alpha-catenin deregulated co-expression in thyroid carcinoma based on tissue microarray digital image analysis. AB - PURPOSE: Deregulation of cell-to-cell adhesion molecules is a common and also critical genetic event in epithelial malignancies leading to an increasing metastatic potential. Among them, e-cadherin and catenins--especially alpha and beta--, act as oncogenes during the carcinogenetic process affecting specific signaling transduction pathways (i.e. Wnt/ b-catenin). Concerning thyroid carcinoma, decreased or loss of expression in these proteins seems to affect the biological behavior of the neoplasm increasing its aggressiveness. The aim of this study was to investigate the deregulation of e-cadherin/alpha-catenin complex in thyroid carcinomas. METHODS: Thirty-five paraffin-embedded tissue samples including thyroid carcinomas (N=20) and also 15 cases of benign follicular nodules were cored at 1 mm diameter and transferred to a microarray block. Immunohistochemistry (IHC) was performed using anti-e-cadherin/alpha catenin antibodies. Digital image analysis was also implemented for measuring the corresponding protein expression levels. RESULTS: E-cadherin/alpha-catenin protein expression demonstrated a significant progressive decrease regarding benign and malignant lesions (p=0.001). Simultaneous e-cadherin/alpha-catenin reduced or loss of expression was observed in 10/20 (50%) cancer cases correlated to advanced stage (especially nodal metastasis) of the examined tumours (p=0.02). Concerning the histological type, combined loss of e-cadherin/alpha-catenin expression was predominantly associated with follicular and anaplastic histology (p=0.001). Interestingly, alpha-catenin protein expression pattern was significantly correlated with the grade of differentiation of the examined malignancies (p=0.01). CONCLUSIONS: Progressive loss of e-cadherin mainly and also alpha-catenin expression is associated with an aggressive phenotype (low differentiation, increased metastatic activity/advanced stage) in thyroid carcinomas. Based on their aberrant protein expression, novel agents have been developed for restoring their normal function. PMID- 27273958 TI - Multicenter experience of adult medulloblastoma: A study of Anatolian Society of Medical Oncology (ASMO). AB - PURPOSE: Medulloblastoma (MB) is rarely seen in adults. For adjuvant therapy in adults the same therapy protocols used in pediatric cases are used. The present study retrospectively evaluated the data of MB patients who were treated in different Oncology Centers in Turkey. METHODS: The data of 60 adult patients with MB from 8 Oncology Centers diagnosed between 2005 and 2012 were retrospectively analyzed. RESULTS: The median patient age was 28.8 years (range 16-54). The administered chemotherapy included procarbazine+lomustin+vincristine (group A, N=31) and cyclophosphamide/ifosfamide+vincristine+cisplatin (group B, N=13). Median chemotherapy courses were 4 (range 1-8). Median progression free survival (PFS) was 76 months and median overall survival (OS) has not been reached in both groups. In young female patients and in those who received adjuvant chemotherapy, median PFS and OS were longer but without statistical significance. Mean PFS and OS were 65.9 months and 101.2 months in group A and 113.6 months and 141.6 months in group B, respectively. CONCLUSION: Improved survival results were obtained in women, in patients aged below 25 years, in those who underwent gross total excision (GTE) and in those who received adjuvant therapy with cyclophosphamide/ifosphamide. PMID- 27273959 TI - Multidrug resistance and tumor-initiating capacity of oral cancer stem cells. AB - PURPOSE: Recent studies in several tumors showed that presence of cancer stem like side population (SP) cells are responsible for chemotherapeutic drugs resistance and tumor relapse. In our present study, we have analyzed the role of SP cells in oral squamous cell carcinoma cell (OSCC) line OSCC-77. METHODS: The oral cancer cell line OSCC-77 was analyzed for the presence of SP cells by FACS using Hoechst 33342 dye exclusion method. Further the FACS-sorted SP and non-SP cells were subjected to drug resistance and sphere formation assays. RESULTS: We identified that the presence of SP cells in OSCC-77 cell line was 3.4%, which was reduced to 0.6% in the presence of verapamil, an inhibitor of ABC transporter. Furthermore, we showed that these SP cells were highly drug-resistant, had increased survival and were highly potent for self-renewal. Also, the clone formation efficiency of SP cells was significantly higher compared to non-SP cells (p<0.01). CONCLUSION: Our data suggest that cancer stem-like SP cells of OSCC-77 cell line contribute to multidrug resistance and are highly involved in tumor relapse. However, further characterization of SP cells at gene expression level and their signaling pathways might provide new insights into the development of novel anticancer drugs. PMID- 27273960 TI - Strategic management of Public Hospitals' medical services. AB - Purpose: The quality of medical services provided by competing public hospitals is the primary consideration of the public in determining the selection of a specific hospital for treatment. The main objective of strategic planning is to improve the quality of public hospital medical services. This paper provides an introduction to the history, significance, principles and practices of public hospital medical service strategy, as well as advancing the opinion that public hospital service strategy must not merely aim to produce but actually result in the highest possible level of quality, convenience, efficiency and patient satisfaction. PMID- 27273961 TI - Policy and Practice Model of Public-Private Partnership in Public Hospitals during the New Medical Reform Period. AB - Purpose: Since the beginning of the new health care reform in 2009, the state has illustrated the top design and health care improvement strategy of "encouraging social capital to participate in the reform of public hospitals", in accordance with the program's general objective. All areas have been explored on this matter and the results obtained are very interesting, not to mention the acquisition of significant experience. At present, the existing business models in China are mainly the following: Rebuild-Operate-Transfer (ROT), franchise business model, Build-Own-Operate-Transfer (BOOT) model, mixed ownership model and business insurance model. This paper introduces a variety of alternative models, and provides a simple analysis of the advantages and disadvantages. Moreover, for the reform of public hospitals, the government shares should go into franchise mode or mixed ownership, and all property rights should be transferred to the government to ensure the conservation and proliferation of state-owned assets. PMID- 27273962 TI - Anticancer activity of two ruthenium(II)-DMSO-chalcone complexes: Comparison of cytotoxic, pro-apoptotic and antimetastatic potential. AB - PURPOSE: Recently, we reported the synthesis and characterization of two complexes of general formula cis-[Ru(S-DMSO)3(R-CO-CH=CH-R')Cl] (R = 2 hydroxyphenyl for both, R' = thiophene (1), 3-methyl thiophene (2)) that showed remarkable topoisomerase II inhibition and strong binding with DNA. The aim of this study was the investigation of cytotoxic properties of these complexes against a panel of human tumor cell lines, with elucidation of their anticancer mechanisms in HeLa cells. METHODS: Characterization of anticancer activity of the investigated ruthenium complexes 1 and 2 included analysis of cytotoxicity by MTT assay. Cell cycle phase disruption of HeLa cells treated with complexes 1 and 2 was analyzed by flow cytometry after propidium iodide (PI) staining. Annexin V FITC/PI double staining and further flow cytometry analysis and acridine orange (AO)/ethidium bromide (EB) double staining and fluorescent microscopy were used to determine the apoptotic potential of the investigated ruthenium complexes. The inhibitory effect on gelatinases (MMP-2 and MMP-9) as an indication of possible antimetastatic potential was also analyzed using gelatine zymography. RESULTS: The 50% cell growth inhibition (IC50) values of the investigated complexes ranged between 22.9 and 76.8 MUM, with complex 2 being more cytotoxic. Both complexes induced G2 phase cell cycle arrest and apoptosis in HeLa cells. Inhibitory effect of complex 2 on MMP-2 activity was detected. CONCLUSIONS: This work revealed the potential of the investigated Ru(II)-DMSO-chalcone complexes as anticancer agents with cytotoxic and pro-apoptotic activity and indicated complex 2 as leading compound for further chemical modifications and anticancer research. PMID- 27273963 TI - New evidence of TERT rs2736098 polymorphism and cancer risk: an updated meta analysis. AB - PURPOSE: Previous meta-analyses didn't suggest any significant association between TERT rs2736098 polymorphism and overall cancer risk, and the existing evidence lacks statistical power to draw a convincing conclusion. METHODS: Herein we performed an update meta-analysis to re-evaluate the association between rs2736098 polymorphism and the risk of overall cancer with all the case-control studies published before March 2015 according to PubMed and Embase databases. RESULTS: A total of 19 case-control studies were included in this analysis. We found that variant genotypes of rs2736098 (GA/AA) were significantly associated with an increased risk of overall cancer (GA/AA vs GG: OR=1.14; 95% CI=1.04 1.25). Additionally, the association was more significant in Asians (OR=1.20; 95% CI=1.07-1.34), while in subsequent analyses stratified by cancer type, the variant rs2736098 was definitely associated with increased lung cancer (OR=1.18; 95% CI=1.07-1.29) and hepatocellular carcinoma risk (OR=1.38; 95% CI=1.20-1.59). CONCLUSION: These findings provided further evidence that TERT rs2736098 variant may modify the susceptibility to cancer. PMID- 27273964 TI - Pelvic intraoperative iatrogenic oncosurgical injuries: single-center experience. AB - PURPOSE: Iatrogenic events are more likely to occur during surgical treatment of malignant conditions. Gynecologic and colorectal cancers account for most of the cases that require surgical treatment within the pelvic area. The purpose of this study was to analyze the incidence of intraoperative accidents and the most frequently encountered injuries during surgery for cancers of the pelvic area. METHODS: The records of 2702 patients admitted to our clinic over a 15-year period, (January 2000-December 2014), were analyzed for type and frequency of intraoperative accidents. RESULTS: Urinary tract lesions were the most common injuries seen in this series (63.1%), followed by enteral (28.1%) and vascular (8.8%) injuries, with an overall incidence of 2.9% for the whole group. Iatrogenic injuries showed a statistically significant difference in incidence depending on the type of primary malignancy (p<0.002). Cervical cancer was associated with a higher rate of ureteral lesions, whereas enteral injuries occurred predominantly during surgical resection for ovarian cancer. The use of neoadjuvant radiotherapy or chemotherapy has been associated with a significantly lower risk of surgical iatrogenic injuries (p=0.004). CONCLUSION: Immediate recognition of the lesion and prompt treatment are recommended in order to lower postoperative complications and to avoid a second operation. PMID- 27273965 TI - Determination of patient set-up error and optimal treatment margin for intensity modulated radiotherapy using image guidance system. AB - PURPOSE: The geometrical uncertainties in the patient positioning during intensity modulated radiotherapy (IMRT) are crucial as there is potential to underdose the tumor and overdose the nearby critical structures. Image guided techniques provide a solution to assess the patient set-up uncertainties and help determine the optimal planning target volume (PTV) margin to the clinical tumor volume (CTV). METHODS: A retrospective study was conducted to evaluate patient set-up errors along the three translational directions at different treatment sites such as the brain, the head and neck (H&N) and the prostate. A total of 60 patients' set-up error data was analysed to evaluate the systematic and random errors and the optimal CTV-PTV margin. RESULTS: For brain and H&N sites, more than 90, 80 and about 100% of the total image acquisitions were less than 3 mm in lateral, longitudinal and vertical directions respectively. For the prostate cases, the frequency of patient set-up error to be less than 3 mm were 79.7, 75.6 and 80% in lateral, longitudinal and vertical directions respectively. About 0.6% had more than 7 mm error in the lateral and longitudinal directions for the prostate site. CTV-PTV margin of 3.4, 3.4 and 1.9 mm for brain cases, 3.5, 3 and 1.8 mm for H&N cases and 5, 4.6 and 4.5 mm for the prostate cases in the lateral, longitudinal and vertical directions respectively were determined. CONCLUSION: Image guidance is an effective method to evaluate the accuracy of IMRT treatment delivery. The optimal CTV-PTV margin can be determined to ensure adequate dose to CTV, specific to the site. PMID- 27273966 TI - Molecular assays in detecting EGFR gene aberrations: an updated HER2-dependent algorithm for interpreting gene signals; a short technical report. AB - Purpose: Among oncogenes that have already been identified and cloned, Epidermal Growth Factor Receptor (EGFR) remains one of the most significant. Understanding its deregulation mechanisms improves critically patients' selection for personalized therapies based on modern molecular biology and oncology guidelines. Anti-EGFR targeted therapeutic strategies have been developed based on specific genetic profiles and applied in subgroups of patients suffering by solid cancers of different histogenetic origin. Detection of specific EGFR somatic mutations leads to tyrosine kinase inhibitors (TKIs) application in subsets of them. Concerning EGFR gene numerical imbalances, identification of pure gene amplification is critical for targeting the molecule via monoclonal antibodies (mAbs). In the current technical paper we demonstrate the main molecular methods applied in EGFR analyses focused also on new data in interpreting numerical imbalances based on ASCO/ACAP guidelines for HER2 in situ hybridization (ISH) clarifications. PMID- 27273967 TI - Impact of the functional neck dissection in maxillofacial surgical oncology: its role in robotic-based surgery era. AB - Head and neck cancers demonstrate an increased prevalence worldwide. The main therapeutic approaches are still surgery and radiotherapy, although in selective cases novel targeted therapeutic strategies based on monoclonal antibodies (ie anti-EGFR) are also applied. Concerning maxillofacial surgical oncology, a variety of methods has been developed. Among them the functional neck dissection technique seems to be a reliable and significant surgical approach, especially in removing identified cervical metastatic lymph node(s). In this technical paper, we focused on the method, its modifications adding our experience and also the challenges that arise in the modern robotic-based era regarding head and neck surgery. PMID- 27273968 TI - Leg cramps associated with tamoxifen use--possible mechanism and treatment recommendations. PMID- 27273969 TI - When should we give aromatase inhibitors for insomnia; early in the day or after dinner? PMID- 27273970 TI - Which situations require attention during radiotherapy in patients with Behcet's disease-associated malignancy? PMID- 27273971 TI - Popular palliative cancer treatments in 18th--mid 19th century. AB - In the 18th century cancer was an incurable disease and the only therapeutic approach was surgery which was accompanied with several life threatening complications. In the absence of effective cancer treatment, palliative approach was proposed by physicians. Compression, ligation, "cura famis" and treatment by cold were four popular treatments in the 18th century provoking an outbreak of therapeutic illusions in cancer patients and physicians, before being lost in oblivion. PMID- 27273972 TI - Development of a new analytical method for the determination of red beetroot betalains using dispersive solid-phase extraction. AB - The objective of this study was to develop a method for the determination of red beetroot betalains based on the dispersive solid-phase extraction and modified QuEChERS methods followed by micro-high performance liquid chromatography coupled with a mass spectrometer that was equipped with a quadrupole and time-of-flight detector. Currently, new techniques for the extraction of the pigments are necessary and in this study, an extraction of beetroot betalains based on the QuEChERS method was developed for the first time. Twelve variants of the methods with different sorbent combinations were tested. The extraction with 15% methanol and with 0.05% formic acid was performed as a reference method to compare the obtained results. In all of the samples with the addition of sorbents, a lower noise was demonstrated in the obtained results. The betalain concentrations obtained using the tested methods were 0.32-0.54 mg g(-1) , while the value of the reference method was 0.44 mg g(-1) . The method that used the strong ion exchange sorbent (0.44+/-0.05 mg g(-1) ) was the most adequate in terms of analyzed content, related standard deviation value and interference compared to the reference method. It was concluded that the properly modified QuEChERS method can be successfully applied for the determination of red beetroot betalains. PMID- 27273973 TI - IgG4-Related Disease With an Aortoduodenal Fistula After Abdominal Aortic Aneurysm Repair. PMID- 27273974 TI - Determination of Water Vapor Pressure Over Corrosive Chemicals Versus Temperature Using Raman Spectroscopy as Exemplified with 85.5% Phosphoric Acid. AB - A method to determine the water vapor pressure over a corrosive substance was developed and tested with 85.5 +/- 0.4% phosphoric acid. The water vapor pressure was obtained at a range of temperatures from ~25 C to ~200 C using Raman spectrometry. The acid was placed in an ampoule and sealed with a reference gas (either hydrogen or methane) at a known pressure (typically ~0.5 bar). By comparing the Raman signals from the water vapor and the references, the water pressure was determined as a function of temperature. A considerable amount of data on the vapor pressure of phosphoric acid are available in the literature, to which our results could successfully be compared. A record value of the vapor pressure, 3.40 bar, was determined at 210 C. The method required a determination of the precise Raman scattering ratios between the substance, water, and the used reference gas, hydrogen or methane. In our case the scattering ratios between water and reference nu1 Q-branches were found to be 1.20 +/- 0.03 and 0.40 +/- 0.02 for H2 and CH4, respectively. PMID- 27273975 TI - Calorimetry-Derived Composition Vectors to Resolve Component Raman Spectra in Phospholipid Phase Transitions. AB - Multidimensional least squares analysis is a well-established technique for resolving component vibrational spectra from mixed samples or systems. Component resolution of temperature-dependent vibrational spectra is challenging, however, due to the lack of a suitable model for the variation in sample composition with temperature. In this work, analysis of temperature-dependent Raman spectra of lipid membranes is accomplished by using "concentration" vectors independently derived from enthalpy changes determined by differential scanning calorimetry. Specifically, the lipid-bilayer phase transitions of DMPC (1,2-dipalmitoyl-sn glycero-3-phosphocholine) are investigated through Raman spectra acquired from individual, optically trapped vesicles in suspension as a function of temperature. Heat capacity profiles of the same vesicle suspension are measured using differential scanning calorimetry and numerically integrated to generate enthalpy change curves of each phase transition, which are in turn used to construct composition vectors. Multidimensional least squares analysis optimized for a fit to these composition vectors allows resolution of the component spectra corresponding to gel, ripple, and liquid-crystalline phases of the DMPC. The quality of fit of the calorimetry-derived results is confirmed by unstructured residual differences between the data and the model, and a composition variation predicted by the resolved spectra that matches the calorimetry results. This approach to analysis of temperature-dependent spectral data could be readily applied in other areas of materials characterization, where one is seeking to learn about structural changes that occur through temperature-dependent phase transitions. PMID- 27273976 TI - Long-Standing Stability of Silver Nanorod Array Substrates Functionalized Using a Series of Thiols for a SERS-Based Sensing Application. AB - Silver nanorod (AgNR) array substrates were fabricated using an oblique angle thermal evaporation technique; their long-term stability, surface uniformity and reproducibility, which are primary requirements for their widespread realistic application and commercialization, were assessed using surface-enhanced Raman scattering (SERS) spectroscopy. The nanorod surfaces were functionalized using a series of organic thiols, which range from hydrophilic to hydrophobic, to mimic various conditions that often arise during detection of hydrophilic/phobic analytes in a realistic application field. A group of these functionalized substrates was stored in ambient laboratory atmosphere; another in light minimized, moisture-free vacuum; while another was stowed carefully and neatly in water to mimic realistic conditions. The effects of these storing conditions were studied. A surfactant was added to the water to maintain consistent surface wetting in the third group. SERS spectra of nanorod substrates prior to functionalization were also recorded to investigate the effect of adventitious carbonaceous contaminants. A meticulous systematic study on the reproducibility of SERS signals was carried out: spot-to-spot, substrate-to-substrate, batch-to batch, day-to-day. The relative standard deviation (RSD) shown by the SERS signals acquired from various spots of a single substrate was less than 3%, which is very similar to the only account reported so far, in which RSD is reported as 2%. The wetting behavior of these thiol functionalized AgNR substrates are investigated using static contact angle measurements. The functionalized substrates have exhibited excellent long-standing stability over a period of six months when stored appropriately; hence, they are highly suitable for mass production towards realistic application. PMID- 27273977 TI - Fuchs' endothelial corneal dystrophy: a controlled prospective study on visual recovery after endothelial keratoplasty. AB - PURPOSE: To investigate the determining factors of vision and subjective outcome after Descemet's stripping automated endothelial keratoplasty (DSAEK) for Fuchs' endothelial dystrophy (FECD). METHODS: In a prospective study, 41 FECD patients who received DSAEK were compared to 40 cataract patients with normal corneas who received cataract surgery (control group). Subjects were recruited between March 2013 and July 2014. Observational procedures included the following: best corrected visual acuity (BCVA), contrast sensitivity (CS), Catquest-9SF questionnaire, Scheimpflug tomography and anterior OCT. Examinations were carried out before surgery and at 3-, 6- and 12-month follow-up. Main outcome measures were associations between corneal optics and visual parameters, as well as subjective improvement (Catquest-9SF effect size) RESULTS: Best-corrected visual acuity (BCVA) negatively correlated with anterior higher-order aberrations (HOA's) (p < 0.001) and central corneal thickness (p = 0.001). Contrast sensitivity (CS) was negatively correlated with anterior HOA's (p = 0.002) and positively correlated with posterior densitometry (p = 0.008). Catquest-9SF effect size was 1.32 (CI: 1.0-1.6) in the control group, 1.84 (CI: 1.4-2.3) in FECD patients who received phacoemulsification and intra-ocular lens implantation in combination with DSAEK (n = 26) and 1.37 (CI: 0.6-2.1) in pseudophakic FECD patients who received DSAEK (n = 15). CONCLUSIONS: DSAEK surgery leads to considerable improvement in patient-reported outcome in FECD patients. There was a strong correlation between anterior HOA's and vision after DSAEK, suggesting that anterior corneal pathology constitutes the major limitation for visual recovery after DSAEK. PMID- 27273978 TI - Listeriosis downregulates hepatic cytochrome P450 enzymes in sublethal murine infection. AB - PURPOSE: Listeria monocytogenes (Lm) can cross the intestinal barrier in humans and then disseminates into different organs. Invasion of the liver occurs even in sublethal infections, however, knowledge of affected physiological processes is scarce. This study employed a sublethal murine infection model to investigate liver responses systematically by proteomics. EXPERIMENTAL DESIGN: Liver samples from three stages of the sublethal infection covering the initial invasion, the peak of infection, and the clearance phase (1, 3, 9 days postinoculation) were analyzed in comparison to samples from noninfected mice. Apart from flow cytometry and RT-PCRs for immune status control, liver responses were analyzed by quantitative peptide sequencing (HPLC-Orbitrap Fusion) using 4-plex iTRAQ labeling. RESULTS: Accurate MS characterized about 3600 proteins and statistics revealed 15% of the hepatic proteome as regulated. Immunological data as well as protein regulation dynamics strongly indicate stage-specific hepatic responses in sublethal infections. Most notably, this study detected a comprehensive deregulation of drug metabolizing enzymes at all stages, including 25 components of the cytochrome P450 system. CONCLUSIONS AND CLINICAL RELEVANCE: Sublethal Lm infection deregulates hepatic drug metabolizing pathways. This finding indicates the need to monitor drug administration along Lm infections, especially in all patients needing constant medication. PMID- 27273979 TI - Perceptions of Bedside Cardiac Critical Care Registered Nurses on 24 Hour Attending Intensivist Coverage. AB - OBJECTIVE: To elicit the perceptions of bedside critical care nurses toward continual in-house attending coverage and its effect on patient safety, communication, and nursing education. DESIGN: A 5-point Likert-type questionnaire was designed to evaluate the perception of bedside nurses in the pediatric cardiac intensive care unit (PCICU) toward the presence of a 24 hour in-house attending physician. SETTING: Single tertiary referral PCICU in Washington, DC SUBJECTS: The 46 PCICU nurses who participated in the study were separated into two groups based on exposure to the recent implementation of continual in-house attending coverage at our institution. Group one consisted of 14 nurses with only exposure to the new 24/7 in-house coverage while group two encompassed 32 nurses who had experienced both the new and old system (off-site on-demand attending physician). MEASUREMENTS AND MAIN RESULTS: Surveys demonstrated that both groups found that the new system has a positive impact on nursing education (median score of 5) as well as a positive impact on the communication between multidisciplinary teams and between care team and families (median score of 5). Nurses who experienced only the new system scored one point lower (median score of 4) regarding the effect of this staffing model on patient outcomes than nurses who had experienced both systems (median score of 5, P = .016). Between 83% and 98% of all 46 nurses who participated indicated they agree or strongly agree with each of the questions regarding the benefit of 24 hour in-house attending coverage. CONCLUSION: Our study suggests that regardless of differences in experience, pediatric cardiac nurses believe the presence of an on-site intensivist to be beneficial to both nursing and patients. PMID- 27273982 TI - [Expert consensus on induction of human embryonic stem cells into tenocytes]. AB - Embryonic stem cells have unlimited proliferative capacity, which may provide a source of tendon stem/progenitor cells for tissue engineering. Experts of International Science and Technology Collaborative Program of Ministry of Science and Technology have developed a protocol consensus on differentiation of human embryonic stem cells into the tendon cells. The consensus recommends a protocol of two-step generation of human embryonic stem cells into tendon cells: the human embryonic stem cells are first differentiated into mesenchymal stem cells on different material surfaces; then with the scaffold-free tissue engineering tendon formed by high-density planting, the mesenchymal stem cells are induced into tendon cells under static or dynamic mechanical stimulation in vivo and in vitro. Tissue engineering tendon established in vitro by the protocol can be used as a model in toxicological analysis and safety evaluation of tendon-relevant small molecule compounds, medical materials and drugs. PMID- 27273981 TI - Direct and Indirect Determinants of the Patient Global Assessment in Rheumatoid Arthritis: Differences by Level of Disease Activity. AB - OBJECTIVE: In rheumatoid arthritis (RA), the patient global assessment (PGA) has been strongly associated with pain severity, but less often with other measures, including disease activity measures. We tested whether RA activity and psychological measures had direct associations with the PGA or indirect associations that were mediated by pain. We also tested whether the correlates of the PGA differed with the degree of RA activity. METHODS: We studied 260 patients with active RA on 2 visits in a prospective longitudinal study. We used path analysis to test direct and indirect associations of Disease Activity Score in 28 joints (DAS28), morning stiffness, Health Assessment Questionnaire (HAQ), fatigue, physical role limitations, social functioning, depressive symptoms, and health distress with the PGA. RESULTS: Among the 509 visits, the median PGA score was 50 (25th-75th percentile: 24-66). Pain severity had the strongest association with the PGA, but direct associations were also found for morning stiffness severity, health distress, fatigue, and DAS28. Morning stiffness severity, DAS28, health distress, and HAQ were also indirectly associated with the PGA through pain. Among visits with DAS28 >=5.4, pain, morning stiffness severity, and HAQ were the only determinants of the PGA. Among visits with DAS28 <4.2, health distress and age were additional determinants, and fatigue was marginally associated with the PGA. CONCLUSION: Although pain was the strongest determinant of the PGA in RA, morning stiffness severity, health distress, fatigue, and DAS28 were also important. Determinants of the PGA differed with RA activity, with health distress, age, and to a lesser degree, fatigue, contributing only in patients with less active RA. PMID- 27273983 TI - [Application of tendon-derived stem cells and bone marrow-derived mesenchymal stem cells for tendon injury repair in rat model]. AB - OBJECTIVE: To evaluate the application of tendon-derived stem cells (TDSC) and bone marrow-derived mesenchymal stem cells (BMSC) for patellar tendon injury repair in rat model. METHODS: TDSCs and BMSCs were isolated from patellar tendons or bone marrow of healthy SD rats. The patellar tendon injury model was induced in 60 SD rats, then the animals were divided into 3 groups with 20 in each group: rats in TDSC group received transplantation of TDSC with fibrin glue in defected patellar tendon, rats in BMSC group received BMSC with fibrin glue for transplantation and those in control group received fibrin glue only. The gross morphology, histology and biomechanics of the patellar tendon were examined at 1, 2, 4, 6 and 8 weeks after the treatment. RESULTS: Gross observation showed that the tendon defects in TDSC group and BMSC group almost disappeared in week 8, while the boundary of tendon defects in control group was still visible. Histology examination showed that the neo-tendon formation in TDSC group and BMSC group was observed at week 8, while there was no neo-tendon formation in control group. Biomechanics study showed that the ultimate stress and Young Modulus, relative ultimate stress and relative Young Modulus increased with the time going in all groups(all P<0.05); the ultimate stress and Young Modulus, relative ultimate stress and relative Young Modulus of TDSC and BMSC groups were significantly higher than those in control group at week 4, 6 and 8(all P<0.05). There was no difference in ultimate stress and Young Modulus between TDSC group and BMSC group(P>0.05), however, the relative Young Modulus of TDSC group was significantly higher than that in BMSC group at week 8(P<0.05). CONCLUSION: Allogeneic TDSC and BMSC transplantation facilitates the repair of tendon injury and improves the biomechanics of tendon. TDSC is more suitable for in vivo tendon regeneration than BMSC. PMID- 27273984 TI - [Three-dimensional parallel collagen scaffold promotes tendon extracellular matrix formation]. AB - OBJECTIVE: To investigate the effects of three-dimensional parallel collagen scaffold on the cell shape, arrangement and extracellular matrix formation of tendon stem cells. METHODS: Parallel collagen scaffold was fabricated by unidirectional freezing technique, while random collagen scaffold was fabricated by freeze-drying technique. The effects of two scaffolds on cell shape and extracellular matrix formation were investigated in vitro by seeding tendon stem/progenitor cells and in vivo by ectopic implantation. RESULTS: Parallel and random collagen scaffolds were produced successfully. Parallel collagen scaffold was more akin to tendon than random collagen scaffold. Tendon stem/progenitor cells were spindle-shaped and unified orientated in parallel collagen scaffold, while cells on random collagen scaffold had disorder orientation. Two weeks after ectopic implantation, cells had nearly the same orientation with the collagen substance. In parallel collagen scaffold, cells had parallel arrangement, and more spindly cells were observed. By contrast, cells in random collagen scaffold were disorder. CONCLUSION: Parallel collagen scaffold can induce cells to be in spindly and parallel arrangement, and promote parallel extracellular matrix formation; while random collagen scaffold can induce cells in random arrangement. The results indicate that parallel collagen scaffold is an ideal structure to promote tendon repairing. PMID- 27273985 TI - [Fabrication of bioactive tissue engineering scaffold for reconstructing calcified cartilage layer based on three-dimension printing technique]. AB - OBJECTIVE: To fabricate organic-inorganic composite tissue engineering scaffolds for reconstructing calcified cartilage layer based on three-dimensional (3D) printing technique. METHODS: The scaffolds were developed by 3D-printing technique with highly bioactive calcium-magnesium silicate ultrafine particles of 1%, 3% and 5% of mass fraction, in which the organic phases were composed of type I collagen and sodium hyaluronate. The 3D-printed scaffolds were then crosslinked and solidified by alginate and CaCl2 aerosol. The pore size and distribution of inorganic phase were observed with scanning electron microscope (SEM); the mechanical properties were tested with universal material testing machine, and the porosity of scaffolds was also measured. RESULTS: Pore size was approximately (212.3 +/- 34.2) MUm with a porosity of (48.3 +/- 5.9)%, the compressive modulus of the scaffolds was (7.2 +/- 1.2) MPa, which was irrelevant to the percentage changes of calcium-magnesium silicate, the compressive modulus was between that of cartilage and subchondral bone. CONCLUSION: The porous scaffolds for calcified cartilage layer have been successfully fabricated, which would be used for multi layered composite scaffolds in osteochondral injury. PMID- 27273980 TI - High throughput toxicity screening and intracellular detection of nanomaterials. AB - With the growing numbers of nanomaterials (NMs), there is a great demand for rapid and reliable ways of testing NM safety-preferably using in vitro approaches, to avoid the ethical dilemmas associated with animal research. Data are needed for developing intelligent testing strategies for risk assessment of NMs, based on grouping and read-across approaches. The adoption of high throughput screening (HTS) and high content analysis (HCA) for NM toxicity testing allows the testing of numerous materials at different concentrations and on different types of cells, reduces the effect of inter-experimental variation, and makes substantial savings in time and cost. HTS/HCA approaches facilitate the classification of key biological indicators of NM-cell interactions. Validation of in vitro HTS tests is required, taking account of relevance to in vivo results. HTS/HCA approaches are needed to assess dose- and time-dependent toxicity, allowing prediction of in vivo adverse effects. Several HTS/HCA methods are being validated and applied for NM testing in the FP7 project NANoREG, including Label-free cellular screening of NM uptake, HCA, High throughput flow cytometry, Impedance-based monitoring, Multiplex analysis of secreted products, and genotoxicity methods-namely High throughput comet assay, High throughput in vitro micronucleus assay, and gammaH2AX assay. There are several technical challenges with HTS/HCA for NM testing, as toxicity screening needs to be coupled with characterization of NMs in exposure medium prior to the test; possible interference of NMs with HTS/HCA techniques is another concern. Advantages and challenges of HTS/HCA approaches in NM safety are discussed. WIREs Nanomed Nanobiotechnol 2017, 9:e1413. doi: 10.1002/wnan.1413 For further resources related to this article, please visit the WIREs website. PMID- 27273986 TI - [Progress and challenges in tissue engineering of intervertebral disc annulus fibrosus]. AB - Degenerative disc disease (DDD) is a leading cause of low back pain, which severely affects the quality of life and incurs significant medical cost. Annulus fibrosus(AF) injuries can lead to substantial deterioration of intervertebral disc degeneration. However, the AF repair/regeneration remains a challenge due to the intrinsic cellular, biochemical and biomechanical heterogeneity of AF tissue. Tissue engineering would be a promising approach for AF regeneration. This article aims to provide a brief overview of the fundamental aspects of AF, the current achievements and future challenges of AF tissue engineering. A multidisciplinary approach is proposed for future studies to fully mimic the native AF tissue and its microenvironment, including choosing adequate cell source, preparing scaffolds with hierarchical microstructures, supplementing appropriate growth factors, and enforcing suitable mechanical stimulation. Hopefully, the engineered AF tissues would be effectively used to facilitate the treatment of DDD in the future. PMID- 27273987 TI - [Research advances of three-dimension printing technology in vertebrae and intervertebral disc tissue engineering]. AB - Three-dimensional (3D) printing technology is characterized by "inside-out" stack manufacturing. Compared with conventional technologies, 3D printing has the advantage of personalization and precision. Therefore, the shape and internal structure of the scaffolds made by 3D printing technology are highly biomimetic. Besides, 3D bioprinting can precisely deposit the biomaterials, seeding cells and cytokines at the same time, which is a breakthrough in printing technique and material science. With the development of 3D printing, it will make great contributions to the reconstruction of vertebrae and intervertebral disc in the future. PMID- 27273988 TI - [Research progress of induced pluripotent stem cells in treatment of muscle atrophy]. AB - Muscle atrophy caused by nerve injury is a common and difficult clinical problem. The development of stem cell researches has opened up a new way for the treatment of nerve injury-induced muscle atrophy. The induced pluripotent stem cells(iPSCs)can differentiate into various types of cells and have more advantages than embryonic stem cells (ESCs). After being transplanted into the damaged area, iPSCs are guided by neurogenic signals to the lesion sites, to repair the damaged nerve, promote generation of axon myelination, rebuild neural circuits and restore physiological function. Meanwhile, iPSCs can also differentiate into muscle cells and promote muscle tissue regeneration. Therefore, it would be possible to attenuate muscle atrophy caused by nerve injury with iPSCs treatment. PMID- 27273989 TI - [Application of silk-based tissue engineering scaffold for tendon / ligament regeneration]. AB - Tendon/ligament injury is one of the most common impairments in sports medicine. The traditional treatments of damaged tissue repair are unsatisfactory, especially for athletes, due to lack of donor and immune rejection. The strategy of tissue engineering may break through these limitations, and bring new hopes to tendon/ligament repair, even regeneration. Silk is a kind of natural biomaterials, which has good biocompatibility, wide range of mechanical properties and tunable physical structures; so it could be applied as tendon/ligament tissue engineering scaffolds. The silk-based scaffold has robust mechanical properties; combined with other biological ingredients, it could increase the surface area, promote more cell adhesion and improve the biocompatibility. The potential clinical application of silk-based scaffold has been confirmed by in vivo studies on tendon/ligament repairing, such as anterior cruciate ligament, medial collateral ligament, achilles tendon and rotator cuff. To develop novel biomechanically stable and host integrated tissue engineered tendon/ligament needs more further micro and macro studies, combined with product development and clinical application, which will give new hope to patients with tendon/ligament injury. PMID- 27273990 TI - [Research progress on application of carbon nanotubes in bone tissue engineering scaffold]. AB - Carbon nanotubes possess excellent mechanical and electrical properties and demonstrate broad application prospects in medical fields. Carbon nanotubes are composed of inorganic materials, natural biodegradable polymer or synthetic biodegradable polymer. The composite bone tissue engineering scaffolds are constructed by particle-hole method, lyophilization, microsphere aggregation method, electrostatic spinning or three-dimensional printing. Composite scaffolds overcome the shortcomings of single material and have good biocompatibility, osteoconduction and osteoinduction. With the study of surface chemistry, toxicology, and biocompatibility, a degradable "human-friendly" carbon nanotubes composite bone tissue scaffold will be available; and under the drive of new fabrication techniques, the clinical application of carbon nanotubes composite bone tissue engineering scaffolds will be better developed. PMID- 27273991 TI - [MicroRNAs: a type of novel regulative factor for intervertebral disc degeneration]. AB - Intervertebral disc degeneration (IDD) is one of major causes for intervertebral disc degenerative diseases, and patients with IDD usually suffer from serious low back pain. The current treatments for patients with IDD only relieve the clinical symptom rather than restore biological balance of IDD, leading to inadequate and unsatisfactory results. MicroRNAs (miRNAs) are endogenous, non-coding, single stranded RNA molecules, which regulate the gene expression at the post transcription levels. Research evidences support the involvement of miRNAs in many biological processes, such as lipid metabolism, apoptosis, differentiation and organ development. Accumulating evidences indicate that the expressions of miRNAs change significantly in degenerative tissues. In addition, dysregulated miRNAs contribute to multiple pathological process of IDD, including proliferation and apoptosis of nucleus pulposus and extracellular matrix components, inflammatory response and cartilage endplates degeneration. In this review article, we summarize the expression profiles and roles of miRNAs in IDD, which may provide a novel strategy of biological therapy for the disease. PMID- 27273992 TI - [Progress on treatment of tendinopathy with platelet-enriched plasma]. AB - Platelet-enriched plasma (PRP) contains high concentration of platelets and abundant growth factors, which is made by centrifuging of blood and separating of blood elements. PRP promotes tendon repair by releasing various cytokines to enhance cell proliferation, tenogenic differentiation, formation and secretion of matrix; meantime, it can reduce pain by inhibiting the expression of pain associated molecules. A number of clinical studies demonstrated that PRP was effective in treatment of tendinopathy, including patellar tendinopathy, lateral epicondylitis and plantar fasciopathy. However, some studies did not support this conclusion, because of disparity of PRP types, therapeutic courses and injections protocols in clinical application. Based on its safety, PRP can be a choice of treatment for tendinopathy, in case other non-surgical therapies are of no effect. PMID- 27273993 TI - [Protective effect of LR-90 on articular cartilage in rabbit model of osteoarthritis]. AB - OBJECTIVE: To investigate the protective effect of LR-90 on articular cartilage in rabbit model of osteoarthritis. METHODS: The cultured rabbits chondrocytes were assigned to be treated with IL-1beta (10ng/ml) or IL-1beta (10ng/ml)+LR-90 (50 mg/L). The mRNA expression of MMP-13, ADAMTS-5, aggrecan and collagen II in chondrocytes were assessed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Twenty male New Zealand white rabbits underwent bilateral anterior cruciate ligament transection (ACLT) to establish a animal model of osteoarthritis. Four weeks after model established, on the basis of randomization one knee of each rabbit was treated with 50 mg/L LR-90 in normal saline (NS) (experimental group) and the other knee was treated with same volume of NS (control group), 1/week * 5. Nine weeks after ACLT all rabbits were sacrificed and the knee joints were evaluated by gross morphology and histology. The mRNA expression of IL-1beta, MMP-13, ADAMTS-5, aggrecan and collagen II in articular cartilage was analyzed by RT-PCR. RESULTS: Gross morphology and Mankin histological evaluation showed that the extent and grade of cartilage damage in the experimental group were less severe than those in the control group.Compared to IL-1beta group, LR-90 treatment suppressed the mRNA expression of MMP-13 and ADAMTS-5, and enhanced aggrecan and collagen II mRNA expression. Consistent with the in vitro results, the intraarticular LR-90 administration suppressed the mRNA expression of IL-1beta,MMP-13 and ADAMTS-5 (all P<0.01), while enhanced mRNA expression of aggrecan and collagen II in cartilage (all P<0.01). CONCLUSION: LR 90 protects against cartilage degradation and inhibits the progression of osteoarthritis in rabbit mode1 of osteoarthritis, which is associated with the suppressing IL-1beta, MMP-13, ADAMTS-5 and promoting aggrecan and collagen II mRNA expression in cartilage. PMID- 27273994 TI - [Effects of interim hemodialysis on survival and clinical outcomes in patients with maintenance peritoneal dialysis]. AB - OBJECTIVE: To investigate the effects of interim hemodialysis (HD) on survival and clinical outcomes in patients with maintenance peritoneal dialysis (PD). METHODS: The clinical data of 908 patients undergoing maintenance PD from January 2010 to December 2014 registered in Zhejiang Dialysis Regisration System were retrospectively analyzed. Among all PD patients, 176 cases received interim HD for less than 3 months, and then transferred to PD (transfer group) and 732 cases had initial PD (non-transfer group). The demographic parameters, biochemical data, comorbidity, details of peritonitis and transplantation were documented. Survival curves were made by the Kaplan-Meier method; univariate and multivariate analyses were performed with Cox proportional hazard regression model to identify risk factors of mortality. RESULTS: Compared with patients in transfer group, patients in non-transfer group had significantly higher serum albumin and total Kt/V levels. The survival rate was significantly higher in non-transfer group, but there was no significant difference in technique survival between two groups. After multivariable adjustment, initial dialysis modality (HR=1.60, 95% CI: 1.01~2.56), age (HR=1.07, 95% CI:1.05~1.09) and serum albumin (HR=0.96, 95% CI: 0.93~0.99) and Charslon comorbidity index (HR=2.54, 95% CI:1.63~3.94) were independent factors for long-term survival. CONCLUSION: Patients who transfer to PD after interim HD have lower survival rate than patients who start with and are maintained on PD. HD is an independent risk factor for PD patients, therefore, patients with PD should be well informed and educated with dialysis protocols. PMID- 27273995 TI - [Characteristics of urinary tract infection in kidney transplant recipients and non-recipient patients]. AB - OBJECTIVE: To compare the characteristics of urinary tract infection (UTI) between kidney transplant recipients and non-recipient patients. METHODS: Forty nine kidney transplant recipients with UTI (69 episodes) and 401 non-recipient patients with UTI (443 episodes) admitted in Nanfang Hospital from January 2003 to August 2014 were enrolled in the study. The characteristics of UTI were compared between two groups. RESULTS: In both groups of UTI, female patients comprised a greater proportion (63.3% and 58.6%) and Escherichia coli was the most common pathogen isolated (37.7% and 34.1%). However, the infection rate of Klebsiella pneumonia in recipients was higher than that in non-recipients (11.6% vs 3.2%, P= 0.001), while the infection rate of Candida albicans was lower (1.5% vs 11.3%, P=0.008) than that in non-recipients. Recipients were likely to develop antibiotic resistance and with a higher recurrence rate than non-recipient patients (38.8% vs 16.7%, P<0.001). Compared to non-recipient UTI patients, the symptoms of urinary irritation in recipient UTI patients were more common. There was higher percentage of neutrophil granulocyte (72.65% +/- 1.90% vs 68.59% +/- 0.73%, P=0.048), lower proportion of lymphocytes (17.73% +/- 1.27% vs 21.28% +/- 0.61%, P=0.037), and less platelets [(187.64 +/- 10.84) * 10(9)/L vs (240.76 +/- 5.26) * 10(9)/L, P<0.01] in recipients than in non-recipient UTI patients. CONCLUSION: These results indicate that the characteristics of UTI in kidney transplantation recipients and non-recipients patients are different. PMID- 27273996 TI - [Epidemiology of acute kidney injury in hospitalized patients in China]. AB - Acute kidney injury (AKI) is a disease spectrum ranging from minimal elevation of serum creatinine to complete renal failure. It is significantly associated with increased mortality, length of hospital stay and medical care cost. With the increasing awareness of the importance of AKI, several high quality and multicenter epidemiological studies have been published recently in China. However, the results differ a lot due to the differences in regional economic development, the selection of target population and testing indicators, the disease definition and study strategies. The reported incidence of AKI in China is much lower than that in the developed countries. This article will analyze the current status and the problems facing AKI epidemiological studies of hospitalized patients with our own data and those from literature. The article intends to clarify the burden of AKI,to increase the awareness of AKI among clinicians and policy makers for achieving the goal of "zero by 2025" in China. PMID- 27273997 TI - [New insight in pathogenesis of podocyte disfunction in minimal change disease]. AB - Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Its main histology is the fusion of podocyte foot process. The pathogenesis of MCD is not clear, but previously it was thought to be related to immune mechanism. In recent years more studies show that podocyte injury is the key link in the pathogenesis of MCD. In MCD mouse model and human kidney tissues, the expressions of podocyte slit membrane protein-nephrin and podocin, skeleton protein-synaptopodin are decreased, and the expression of synaptopodin is correlated with the response to hormone therapy. In addition, newest studies focused on another two potocyte associated proteins, CD80 and Angiopoietin-like 4. CD80, a T cell stimulating molecule, is expressed in potocyte. Kappa B gene sequences can be activated by external microbes, antigens through acting potocytes, which can induce the upregulation of CD80 expression, cytoskeletal protein damage and the glomerular filtration rate changes, resulting in proteinuria. Angiopoietin-like-4 can be expressed in normal potocytes, but over expression of angiopoietin-like-4 may injure the GBM charge barrier and induce the foot process fusion, leading to MCD. However, further studies on the factors inducing CD80 and Angiopoietin-like-4 expression, and the interaction between glomerular basement membrane and the two proteins are needed. Based on the mechanism of MCD, NF-kappa B inhibitors and sialylation therapy would be a novel non-immune therapy for MCD. PMID- 27273998 TI - Pulmonary Function Parameters Other Than Vital Capacity Should Be Considered in Screening for Interstitial Lung Disease in Patients With Systemic Sclerosis: Comment on the Article by Suliman et al. PMID- 27273999 TI - A proof-of-concept study in engineering synthetic protein for selective recognition of substrate-free polyubiquitin. AB - Similar to substrate-conjugated polyubiquitin, unanchored polyubiquitin chains are emerging as important regulators for diverse biological processes. The affinity purification of unanchored polyubiquitin from various organisms has been reported, however, tools able to distinguish unanchored polyubiquitin chains with different isopeptide linkages have not yet been described. Toward the goal of selectively identifying and purifying unanchored polyubiquitin chains linked through different Lysines, Scott et al. developed a novel strategy in their study [Proteomics 2016, 16, 1961-1969]. They designed a linker-optimized ubiquitin binding domain hybrid (t-UBD) containing two UBDs, a ZnFCUBP domain, and a linkage-selective UBA domain, to specifically recognize unanchored Lys48-linked polyubiquitin chains. Subsequently, a series of assays has proved the feasibility of this novel strategy for the purification of endogenous substrate-free Lys48 linked polyubiquitin chains from mammalian cell extracts. Their research not only provides a tool for purifying unanchored polyubiquitin with different isopeptide linkages, but also paves the way for generating reagents to study the function of unanchored polyubiquitin chains of different linkages in the future. The design of UBD hybrids for defined unanchored polyubiquitin (Lys48-polyubiquitin) in this study also set an excellent example for future methodology studies regarding monitoring in vivo dynamic changes in the patterns of ubiquitination. PMID- 27274000 TI - Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine. AB - Acute phase proteins (APPs) are highly conserved plasma proteins that are increasingly secreted by the liver in response to a variety of injuries, independently of their location and cause. APPs favor the systemic regulation of defense, coagulation, proteolysis, and tissue repair. Various APPs have been applied as general diagnostic parameters for a long time. Through proteomic techniques, more and more APPs have been discovered to be differentially altered. Since they are not consistently explainable by a stereotypic hepatic expression of sets of APPs, most of these results have unfortunately been neglected or attributed to the nonspecificity of the acute phase reaction. Moreover, it appears that various extrahepatic tissues are also able to express APPs. These extrahepatic APPs show focally specific roles in tissue homeostasis and repair and are released primarily into interstitial and distal fluids. Since these focal proteins might leak into the circulatory system, mixtures of hepatic and extrahepatic APP species can be expected in blood. Hence, a selective alteration of parts of APPs might be expected. There are several hints on multiple molecular forms and fragments of tissue-derived APPs. These differences offer the chance for multiple selective determinations. Thus, specific proteoforms might indeed serve as tissue-specific disease indicators. PMID- 27274001 TI - Contributions of prestrains, hyperelasticity, and muscle fiber activation on mitral valve systolic performance. AB - The present study addresses the contributions of prestrains and muscle fiber activation to the global response of the mitral valve during systole. A finite element model of a porcine mitral valve is created using anatomical measurements and 3D echocardiographic recordings. The passive behavior of the leaflets is modeled using a transversely isotropic hyperelastic constitutive model, and we assume orthotropic muscle activations in the anterior leaflet. A simple approach to incorporate prestrains in the mitral valve apparatus is used by expanding the mitral annulus before applying the ventricular pressure to the mitral leaflets. Several finite element analyses are run with or without muscle activation and with or without prestrains. The analysis results are compared at peak systole with the echocardiograpic recordings. The case where prestrains and activation are accounted for simultaneously is the most efficient to approach the physiological flat shape of the closed valve observed in the echocardiograpic measurements. These results suggest that the active components present in the mitral leaflets and the presence of prestrains contribute to the physiological deformations of the mitral valve at peak systole and that material models based on in vitro mechanical testing are not sufficient for numerical studies of the mitral apparatus. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27274002 TI - Relative Bioavailability and Bioequivalence of Brivaracetam 10 mg/mL Oral Solution and 50-mg Film-Coated Tablet. PMID- 27274004 TI - Cell structure imaging with bright and homogeneous nanometric light source. AB - Label-free optical nano-imaging of dendritic structures and intracellular granules in biological cells is demonstrated using a bright and homogeneous nanometric light source. The optical nanometric light source is excited using a focused electron beam. A zinc oxide (ZnO) luminescent thin film was fabricated by atomic layer deposition (ALD) to produce the nanoscale light source. The ZnO film formed by ALD emitted the bright, homogeneous light, unlike that deposited by another method. The dendritic structures of label-free macrophage receptor with collagenous structure-expressing CHO cells were clearly visualized below the diffraction limit. The inner fiber structure was observed with 120 nm spatial resolution. Because the bright homogeneous emission from the ZnO film suppresses the background noise, the signal-to-noise ratio (SNR) for the imaging results was greater than 10. The ALD method helps achieve an electron beam excitation assisted microscope with high spatial resolution and high SNR. PMID- 27274003 TI - Small Traditional Human Communities Sustain Genomic Diversity over Microgeographic Scales despite Linguistic Isolation. AB - At least since the Neolithic, humans have largely lived in networks of small, traditional communities. Often socially isolated, these groups evolved distinct languages and cultures over microgeographic scales of just tens of kilometers. Population genetic theory tells us that genetic drift should act quickly in such isolated groups, thus raising the question: do networks of small human communities maintain levels of genetic diversity over microgeographic scales? This question can no longer be asked in most parts of the world, which have been heavily impacted by historical events that make traditional society structures the exception. However, such studies remain possible in parts of Island Southeast Asia and Oceania, where traditional ways of life are still practiced. We captured genome-wide genetic data, together with linguistic records, for a case-study system-eight villages distributed across Sumba, a small, remote island in eastern Indonesia. More than 4,000 years after these communities were established during the Neolithic period, most speak different languages and can be distinguished genetically. Yet their nuclear diversity is not reduced, instead being comparable to other, even much larger, regional groups. Modeling reveals a separation of time scales: while languages and culture can evolve quickly, creating social barriers, sporadic migration averaged over many generations is sufficient to keep villages linked genetically. This loosely-connected network structure, once the global norm and still extant on Sumba today, provides a living proxy to explore fine-scale genome dynamics in the sort of small traditional communities within which the most recent episodes of human evolution occurred. PMID- 27274005 TI - Acute retinal necrosis and ocular neovascularization caused by cytomegalovirus following intravitreal dexamethasone implant (Ozurdex(r) ) in an immunocompetent patient. PMID- 27274006 TI - Chest Ultrasonography as a Screening Tool for High-Resolution Computed Tomography Referral in Patients With Systemic Sclerosis-A Future Perspective: Comment on the Article by Suliman et al. PMID- 27274007 TI - Pharmacokinetic and Pharmacodynamic Drug Interaction Study of Piragliatin, a Glucokinase Activator, and Glyburide, a Sulfonylurea, in Type 2 Diabetic Patients. AB - A glucokinase activator and a sulfonylurea might be coprescribed to synergize treatment success for type 2 diabetes (T2D). This clinical pharmacology study was designed to investigate the potential glucose-lowering effect or pharmacodynamic (PD), pharmacokinetic (PK), and safety/tolerability interactions between piragliatin and glyburide in T2D patients already taking glyburide but not adequately controlled. This was an open-label, multiple-dose, 3-period, single sequence crossover design: on days -1, 6, and 12, PD and PK samples were drawn with glyburide alone (period 0), piragliatin + glyburide (period 1), and piragliatin alone (period 2) treatments. The glucose-lowering effect, including fasting plasma glucose (FPG), of piragliatin was more pronounced when it was administered concomitantly with glyburide as compared to piragliatin or glyburide administered alone. However, this enhancement cannot be explained by a potential PK interaction between piragliatin and glyburide. Other than hypoglycemia, there were no clinically relevant safety findings. Thus, the enhanced PD effect warrants further investigation to define the optimal dose combination between glucokinase activators and sulfonylureas with regard to efficacy, safety, and tolerability. PMID- 27274008 TI - HLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Disease Activity, and the Health Assessment Questionnaire Score in Patients With Inflammatory Polyarthritis. AB - OBJECTIVE: Rheumatoid arthritis (RA) susceptibility HLA-DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes. METHODS: We tested the association of RA susceptibility HLA-DRB1 amino acids with the C-reactive protein (CRP) level, the tender joint count (TJC), the swollen joint count (SJC), the Disease Activity Score in 28 joints (DAS28), and the Health Assessment Questionnaire (HAQ) score in the Norfolk Arthritis Register (NOAR) and Early Rheumatoid Arthritis Study (ERAS) cohorts. Longitudinal modeling of disease activity/outcomes was performed using generalized linear latent and mixed models. Mediation analysis was performed using directed acyclic graphs to investigate the paths from genetic factors to outcome. RESULTS: A total of 2,158 patients were available for analysis in the NOAR cohort. Valine at position 11 showed the strongest association with the CRP level (P = 2.21 * 10-6 ), the SJC (P = 7.51 * 10-6 ), and the DAS28 (P = 0.002); it was marginally associated with the HAQ score (P = 0.044) but not with the TJC. The same amino acid and haplotype risk hierarchy observed for susceptibility and radiographic severity was observed for the CRP level and nonradiographic measures of disease activity/outcome, apart from the TJC. The results were replicated in the ERAS cohort. The effect of valine at position 11 on the SJC was mainly mediated by anti-citrullinated protein antibody status, the effect of which was mainly mediated by inflammation; however, the effect of valine at position 11 was also independent of the CRP level (P = 1.6 * 10-4 ). CONCLUSION: Genetic markers of RA susceptibility located within HLA-DRB1 determine the levels of clinical and systemic inflammation independently, and also determine all objective measures of disease activity and outcome. PMID- 27274009 TI - Effect of Pradigastat, a Diacylglycerol Acyltransferase 1 Inhibitor, on the QTcF Interval in Humans. AB - Pradigastat, a novel diacylglycerol acyltransferase 1 inhibitor, has been studied in familial chylomicronemia syndrome. To evaluate the effects of supratherapeutic concentrations of pradigastat on the QTc interval, 2 studies were conducted. The first study assessed the safety, tolerability, and pharmacokinetics of single escalating intravenous doses of pradigastat (10, 30, 100, and 115 mg over 60 minutes) in healthy adults. Single intravenous doses were safe, well tolerated, and at the higher doses resulted in supratherapeutic pradigastat exposure. The second was a parallel, 3-arm thorough QTc study in which healthy male subjects were randomized to pradigastat (115 mg intravenously), moxifloxacin (400 mg oral, positive control), or placebo. Following intravenous administration, pradigastat exposure peaked at 4 times the therapeutic concentration and did not prolong the baseline-adjusted and placebo-corrected QTc intervals. During the 60-minute pradigastat infusion, a number of infusion reactions and a small mean decrease in QTc were observed. Both effects disappeared when the infusion was stopped, suggesting that an infusate excipient may have been responsible. As expected, moxifloxacin significantly increased the QTc interval at multiple points, confirming the study's sensitivity to detect a true positive effect. Pradigastat is therefore unlikely to increase the risk of dysrhythmias associated with QTc prolongation in humans. PMID- 27274010 TI - A Novel Mechanism for Generating the Interferon Signature in Lupus: Opsonization of Dead Cells by Complement and IgM. AB - OBJECTIVE: In vitro studies suggest that the type I interferon (IFN) signature seen in most lupus patients results from Fcgamma receptor-mediated uptake of nucleic acid-containing immune complexes by plasmacytoid dendritic cells and engagement of endosomal Toll-like receptors. The aim of this study was to reexamine the pathogenesis of the IFN signature in vivo. METHODS: Lupus was induced in mice by injecting pristane. Some mice were treated with normal immunoglobulin or with cobra venom factor to deplete complement. The IFN signature was evaluated by polymerase chain reaction. The IFN signature also was determined in C4-deficient patients and control subjects. RESULTS: Wild-type C57BL/6 mice with pristane-induced lupus developed a strong IFN signature, which was absent in immunoglobulin-deficient (MUMT), C3-/- , and CD18-/- mice. Intravenous infusion of normal IgM, but not IgG, restored the IFN signature in MUMT mice, and the IFN signature in wild-type mice was inhibited by depleting complement, suggesting that opsonization by IgM and complement is involved in IFN production. Consistent with that possibility, the levels of "natural" IgM antibodies reactive with dead cells were increased in pristane-treated wild-type mice compared with untreated controls, and in vivo phagocytosis of dead cells was impaired in C3-deficient mice. To examine the clinical relevance of these findings, we identified 10 C4-deficient patients with lupus-like disease and compared them with 152 C4-intact patients and 21 healthy controls. In comparison with C4-intact patients, C4-deficient patients had a different clinical/serologic phenotype and lacked the IFN signature. CONCLUSION: These studies define previously unrecognized roles of natural IgM, complement, and complement receptors in generating the IFN signature in lupus. PMID- 27274011 TI - Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease. AB - Methotrexate is an efficacious immunosuppressant for induction and maintenance of remission in Crohn's disease. The goal of this pilot study was to determine whether total or individual methotrexate glutamate levels (MTXGlun ) in red blood cells correlate with disease activity and adverse events in Crohn's disease. A cross-sectional study was undertaken with 12 patients on a stable dose of 25 mg weekly methotrexate (oral or subcutaneous). Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI), and biologic disease activity was measured by inflammatory markers. Concentrations of individual MTXGlun levels were measured in red blood cells (RBCs) using high-performance liquid chromatography-mass spectrometry. No association was observed between RBC individual (MTXGlun ) or total methotrexate glutamate concentrations and clinical disease activity (HBI score) or inflammatory markers or adverse events. Although Crohn's disease patients in remission appeared to generally have higher RBC total longer-chain methotrexate polyglutamate (MTXGlu3+4+5 ) concentrations compared with those with active disease, a definitive association between RBC MTXGlu3+4+5 levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlun levels as indicators of treatment efficacy and clinical outcome. PMID- 27274012 TI - SMART-on-FHIR implemented over i2b2. AB - We have developed an interface to serve patient data from Informatics for Integrating Biology and the Bedside (i2b2) repositories in the Fast Healthcare Interoperability Resources (FHIR) format, referred to as a SMART-on-FHIR cell. The cell serves FHIR resources on a per-patient basis, and supports the "substitutable" modular third-party applications (SMART) OAuth2 specification for authorization of client applications. It is implemented as an i2b2 server plug in, consisting of 6 modules: authentication, REST, i2b2-to-FHIR converter, resource enrichment, query engine, and cache. The source code is freely available as open source. We tested the cell by accessing resources from a test i2b2 installation, demonstrating that a SMART app can be launched from the cell that accesses patient data stored in i2b2. We successfully retrieved demographics, medications, labs, and diagnoses for test patients. The SMART-on-FHIR cell will enable i2b2 sites to provide simplified but secure data access in FHIR format, and will spur innovation and interoperability. Further, it transforms i2b2 into an apps platform. PMID- 27274013 TI - Effectiveness of computer-aided learning in oral health among patients and caregivers: a systematic review. AB - : Computer-aided learning (CAL) offers enormous potential in disseminating oral health care information to patients and caregivers. The effectiveness of CAL, however, remains unclear. OBJECTIVES: The purpose of this study was to systematically review published evidence on the effectiveness of CAL in disseminating oral health care information to patients and caregivers. MATERIALS AND METHODS: A structured comprehensive search was undertaken among 7 electronic databases (PUBMED, CINAHL Plus, EMBASE, SCOPUS, WEB of SCIENCE, the Cochrane Library, and PsycINFO) to identify relevant studies. Randomized controlled trials (RCTs) and observational studies were included in this review. Papers were screened by 2 independent reviewers, and studies that met the inclusion criteria were selected for further assessment. RESULTS: A total of 2915 papers were screened, and full texts of 53 potentially relevant papers (kappa = 0.885) were retrieved. A total of 5 studies that met the inclusion criteria (1 RCT, 1 quasi experimental study, and 3 post-intervention studies) were identified. Outcome measures included knowledge, attitude, behavior, and oral health. Significant improvements in clinical oral health parameters (P < .05) and knowledge/attitudes (P < .001) were reported in 2 of the studies. The 3 remaining studies reported improved oral health behaviors and confidence. CONCLUSION: There is a limited number of studies which have examined the effectiveness of CAL interventions for oral health care among patients and caregivers. Synthesis of the data suggests that CAL has positive impacts on knowledge, attitude, behavior, and oral health. Further high- quality studies on the effectiveness of CAL in promoting oral health are warranted. PMID- 27274014 TI - Which veterans enroll in a VA health information exchange program? AB - OBJECTIVE: To characterize patients who voluntarily enrolled in an electronic health information exchange (HIE) program designed to share data between Veterans Health Administration (VHA) and non-VHA institutions. MATERIALS AND METHODS: Patients who agreed to participate in the HIE program were compared to those who did not. Patient characteristics associated with HIE enrollment were examined using a multivariable logistic regression model. Variables selected for inclusion were guided by a health care utilization model adapted to explain HIE enrollment. Data about patients' sociodemographics (age, gender), comorbidity (Charlson index score), utilization (primary and specialty care visits), and access (distance to VHA medical center, insurance, VHA benefits) were obtained from VHA and HIE electronic health records. RESULTS: Among 57 072 patients, 6627 (12%) enrolled in the HIE program during its first year. The likelihood of HIE enrollment increased among patients ages 50-64, of female gender, with higher comorbidity, and with increasing utilization. Living in a rural area and being unmarried were associated with decreased likelihood of enrollment. DISCUSSION AND CONCLUSION: Enrollment in HIE is complex, with several factors involved in a patient's decision to enroll. To broaden HIE participation, populations less likely to enroll should be targeted with tailored recruitment and educational strategies. Moreover, inclusion of special populations, such as patients with higher comorbidity or high utilizers, may help refine the definition of success with respect to HIE implementation. PMID- 27274015 TI - Alert override as a habitual behavior - a new perspective on a persistent problem. AB - Quantifying alert override has been the focus of much research in health informatics, with override rate traditionally viewed as a surrogate inverse indicator for alert effectiveness. However, relying on alert override to assess computerized alerts assumes that alerts are being read and determined to be irrelevant by users. Our research suggests that this is unlikely to be the case when users are experiencing alert overload. We propose that over time, alert override becomes habitual. The override response is activated by environmental cues and repeated automatically, with limited conscious intention. In this paper we outline this new perspective on understanding alert override. We present evidence consistent with the notion of alert override as a habitual behavior and discuss implications of this novel perspective for future research on alert override, a common and persistent problem accompanying decision support system implementation. PMID- 27274016 TI - An electronic documentation system improves the quality of admission notes: a randomized trial. AB - OBJECTIVE: There are concerns that structured electronic documentation systems can limit expressivity and encourage long and unreadable notes. We assessed the impact of an electronic clinical documentation system on the quality of admission notes for patients admitted to a general medical unit. METHODS: This was a prospective randomized crossover study comparing handwritten paper notes to electronic notes on different patients by the same author, generated using a semistructured electronic admission documentation system over a 2-month period in 2014. The setting was a 4-team, 80-bed general internal medicine clinical teaching unit at a large urban academic hospital. The quality of clinical documentation was assessed using the QNOTE instrument (best possible score = 100), and word counts were assessed for free-text sections of notes. RESULTS: Twenty-one electronic-paper note pairs (42 notes) written by 21 authors were randomly drawn from a pool of 303 eligible notes. Overall note quality was significantly higher in electronic vs paper notes (mean 90 vs 69, P < .0001). The quality of free-text subsections (History of Present Illness and Impression and Plan) was significantly higher in the electronic vs paper notes (mean 93 vs 78, P < .0001; and 89 vs 77, P = .001, respectively). The History of Present Illness subsection was significantly longer in electronic vs paper notes (mean 172.4 vs 92.4 words, P = .0001). CONCLUSIONS: An electronic admission documentation system improved both the quality of free-text content and the overall quality of admission notes. Authors wrote more in the free-text sections of electronic documents as compared to paper versions. PMID- 27274017 TI - Computer use, language, and literacy in safety net clinic communication. AB - OBJECTIVE: Patients with limited health literacy (LHL) and limited English proficiency (LEP) experience suboptimal communication and health outcomes. Electronic health record implementation in safety net clinics may affect communication with LHL and LEP patients.We investigated the associations between safety net clinician computer use and patient-provider communication for patients with LEP and LHL. MATERIALS AND METHODS: We video-recorded encounters at 5 academically affiliated US public hospital clinics between English- and Spanish speaking patients with chronic conditions and their primary and specialty care clinicians. We analyzed changes in communication behaviors (coded with the Roter Interaction Analysis System) with each additional point on a clinician computer use score, controlling for clinician type and visit length and stratified by English proficiency and health literacy status. RESULTS: Greater clinician computer use was associated with more biomedical statements (+12.4, P = .03) and less positive affect (-0.6, P < .01) from LEP/LHL patients. In visits with patients with adequate English proficiency/health literacy, greater clinician computer use was associated with less positive patient affect (-0.9, P < .01), fewer clinician psychosocial statements (-3.5, P < .05), greater clinician verbal dominance (+0.09, P < .01), and lower ratings on quality of care and communication. CONCLUSION: Higher clinician computer use was associated with more biomedical focus with LEP/LHL patients, and clinician verbal dominance and lower ratings with patients with adequate English proficiency and health literacy. DISCUSSION: Implementation research should explore interventions to enhance relationship-centered communication for diverse patient populations in the computer era. PMID- 27274019 TI - Improving the quality of EHR recording in primary care: a data quality feedback tool. AB - OBJECTIVE: Electronic health record (EHR) data are used to exchange information among health care providers. For this purpose, the quality of the data is essential. We developed a data quality feedback tool that evaluates differences in EHR data quality among practices and software packages as part of a larger intervention. METHODS: The tool was applied in 92 practices in the Netherlands using different software packages. Practices received data quality feedback in 2010 and 2012. RESULTS: We observed large differences in the quality of recording. For example, the percentage of episodes of care that had a meaningful diagnostic code ranged from 30% to 100%. Differences were highly related to the software package. A year after the first measurement, the quality of recording had improved significantly and differences decreased, with 67% of the physicians indicating that they had actively changed their recording habits based on the results of the first measurement. About 80% found the feedback helpful in pinpointing recording problems. One of the software vendors made changes in functionality as a result of the feedback. CONCLUSIONS: Our EHR data quality feedback tool is capable of highlighting differences among practices and software packages. As such, it also stimulates improvements. As substantial variability in recording is related to the software package, our study strengthens the evidence that data quality can be improved substantially by standardizing the functionalities of EHR software packages. PMID- 27274018 TI - Precision medicine informatics. PMID- 27274020 TI - Learning temporal rules to forecast instability in continuously monitored patients. AB - Inductive machine learning, and in particular extraction of association rules from data, has been successfully used in multiple application domains, such as market basket analysis, disease prognosis, fraud detection, and protein sequencing. The appeal of rule extraction techniques stems from their ability to handle intricate problems yet produce models based on rules that can be comprehended by humans, and are therefore more transparent. Human comprehension is a factor that may improve adoption and use of data-driven decision support systems clinically via face validity. In this work, we explore whether we can reliably and informatively forecast cardiorespiratory instability (CRI) in step down unit (SDU) patients utilizing data from continuous monitoring of physiologic vital sign (VS) measurements. We use a temporal association rule extraction technique in conjunction with a rule fusion protocol to learn how to forecast CRI in continuously monitored patients. We detail our approach and present and discuss encouraging empirical results obtained using continuous multivariate VS data from the bedside monitors of 297 SDU patients spanning 29 346 hours (3.35 patient-years) of observation. We present example rules that have been learned from data to illustrate potential benefits of comprehensibility of the extracted models, and we analyze the empirical utility of each VS as a potential leading indicator of an impending CRI event. PMID- 27274021 TI - Assessment-based health informatics curriculum improvement. AB - OBJECTIVE: Informatics programs need assurance that their curricula prepare students for intended roles as well as ensuring that students have mastered the appropriate competencies. The objective of this study is to describe a method for using assessment data to identify areas for curriculum, student selection, and assessment improvement. MATERIALS AND METHODS: A multiple-choice examination covering the content in the Commission for Health Accreditation of Informatics and Information Management Education curricular facets/elements was developed and administered to 2 cohorts of entering students prior to the beginning of the program and to the first cohort after completion of the first year's courses. The reliability of the examination was assessed using Cronbach's alpha. Content validity was assessed by having 2 raters assess the match of the items to the Commission for Health Accreditation of Informatics and Information Management Education requirements. Construct validation included comparison of exam performance of instructed vs uninstructed students. Criterion-related validity was assessed by examining the relationship of background characteristics to exam performance and by comparing examination performance to graduate Grade Point Average (GPA). RESULTS: Reliability of the examination was 0.91 and 0.82 (Cohort 1 pre/post-tests) and 0.43 (Cohort 2 pretest). Both raters judged 76% of the test items as appropriate. There were statistically significant differences between the instructed (Cohort 1 post-test) and uninstructed (Cohort 2 pretest) students (t = 2.95 P < .01), as well as between the Cohort 1 pre/post-tests (t = 6.52, P < .001). Neither the background variables nor the graduate GPA were significantly correlated with the examination scores. CONCLUSION: We found that the examination had generally good psychometric properties and the exceptions could be used to identify areas for curriculum and assessment improvement. PMID- 27274022 TI - Health informatics and analytics - building a program to integrate business analytics across clinical and administrative disciplines. AB - Health care organizations must develop integrated health information systems to respond to the numerous government mandates driving the movement toward reimbursement models emphasizing value-based and accountable care. Success in this transition requires integrated data analytics, supported by the combination of health informatics, interoperability, business process design, and advanced decision support tools. This case study presents the development of a master's level cross- and multidisciplinary informatics program offered through a business school. The program provides students from diverse backgrounds with the knowledge, leadership, and practical application skills of health informatics, information systems, and data analytics that bridge the interests of clinical and nonclinical professionals. This case presents the actions taken and challenges encountered in navigating intra-university politics, specifying curriculum, recruiting the requisite interdisciplinary faculty, innovating the educational format, managing students with diverse educational and professional backgrounds, and balancing multiple accreditation agencies. PMID- 27274023 TI - A novel use of the discrete templated notes within an electronic health record software to monitor resident supervision. AB - Objective: Monitoring the supervision of residents can be a challenging task. We describe our experience with the implementation of a templated note system for documenting procedures with the aim of enabling automated, discrete, and standardized capture of documentation of supervision of residents performing floor-based procedures, with minimal extra effort from the residents. Materials and methods: Procedural note templates were designed using the standard existing template within a commercial electronic health record software. Templates for common procedures were created such that residents could document every procedure performed outside of the formal procedural areas. Automated reports were generated and letters were sent to noncompliers. Results: A total of 27 045 inpatient non-formal procedural area procedures were recorded from August 2012 to June 2014. Compliance with NoteWriter template usage averaged 86% in the first year and increased to 94.6% in the second year ( P = .0055). : Initially, only 12.5% of residents documented supervision of any form. By the end of the first year, this was above 80%, with the gains maintained into the second year and beyond. Direct supervision was documented to have occurred where required in 62.8% in the first year and increased to 99.8% in the second year ( P = .0001) after the addition of hard stops. Notification of attendings prior to procedures was documented 100% of the time by September 2013. Letters sent to errant residents decreased from 3.6 to 0.83 per 100 residents per week. Conclusion: The templated procedure note system with hard stops and integrated reporting can successfully be used to improve monitoring of resident supervision. This has potential impact on resident education and patient safety. PMID- 27274024 TI - The organization and content of informatics doctoral dissertations. AB - This article offers suggested guidelines for graduate students who are embarking on informatics doctoral studies and anticipating the dissertation research and its documentation. Much of the guidance is pertinent for writing dissertations in other disciplines as well. The messages are largely directed at doctoral students, but some elements are also pertinent for master's students. All are relevant for faculty research advisors. The value of the dissertation is often underestimated. Too often it is seen as a hurdle to be overcome rather than an opportunity to gain insight into one's own research and to learn how to communicate effectively about it. Ideas that have been ill-formed often do not gel effectively until one tries to write about them. The main lesson is that the preparation of a carefully crafted, rigorous, logically evidence-based, and influential dissertation can be remarkably rewarding, both personally and professionally. PMID- 27274025 TI - Evaluation of clinical information modeling tools. AB - OBJECTIVE: Clinical information models are formal specifications for representing the structure and semantics of the clinical content within electronic health record systems. This research aims to define, test, and validate evaluation metrics for software tools designed to support the processes associated with the definition, management, and implementation of these models. METHODOLOGY: The proposed framework builds on previous research that focused on obtaining agreement on the essential requirements in this area. A set of 50 conformance criteria were defined based on the 20 functional requirements agreed by that consensus and applied to evaluate the currently available tools. RESULTS: Of the 11 initiative developing tools for clinical information modeling identified, 9 were evaluated according to their performance on the evaluation metrics. Results show that functionalities related to management of data types, specifications, metadata, and terminology or ontology bindings have a good level of adoption. Improvements can be made in other areas focused on information modeling and associated processes. Other criteria related to displaying semantic relationships between concepts and communication with terminology servers had low levels of adoption. CONCLUSIONS: The proposed evaluation metrics were successfully tested and validated against a representative sample of existing tools. The results identify the need to improve tool support for information modeling and software development processes, especially in those areas related to governance, clinician involvement, and optimizing the technical validation of testing processes. This research confirmed the potential of these evaluation metrics to support decision makers in identifying the most appropriate tool for their organization. OBJECTIVO: Los Modelos de Informacion Clinica son especificaciones para representar la estructura y caracteristicas semanticas del contenido clinico en los sistemas de Historia Clinica Electronica. Esta investigacion define, prueba y valida un marco para la evaluacion de herramientas informaticas disenadas para dar soporte en la en los procesos de definicion, gestion e implementacion de estos modelos. METODOLOGIA: El marco de evaluacion propuesto se basa en una investigacion previa para obtener consenso en la definicion de requisitos esenciales en esta area. A partir de los 20 requisitos funcionales acordados, un conjunto de 50 criterios de conformidad fueron definidos y aplicados en la evaluacion de las herramientas existentes. RESULTADOS: Un total de 9 de las 11 iniciativas identificadas desarrollando herramientas para el modelado de informacion clinica fueron evaluadas. Los resultados muestran que las funcionalidades relacionadas con la gestion de tipos de datos, especificaciones, metadatos y mapeo con terminologias u ontologias tienen un buen nivel de adopcion. Se identifican posibles mejoras en areas relacionadas con los procesos de modelado de informacion. Otros criterios relacionados con presentar las relaciones semanticas entre conceptos y la comunicacion con servidores de terminologia tienen un bajo nivel de adopcion. CONCLUSIONES: El marco de evaluacion propuesto fue probado y validado satisfactoriamente contra un conjunto representativo de las herramientas existentes. Los resultados identifican la necesidad de mejorar el soporte de herramientas a los procesos de modelado de informacion y desarrollo de software, especialmente en las areas relacionadas con gobernanza, participacion de profesionales clinicos y la optimizacion de la validacion tecnica en los procesos de pruebas tecnicas. Esta investigacion ha confirmado el potencial de este marco de evaluacion para dar soporte a los usuarios en la toma de decisiones sobre que herramienta es mas apropiadas para su organizacion. PMID- 27274026 TI - Long-Term Stability of Volatile Nitrosamines in Human Urine. AB - Volatile nitrosamines (VNAs) are established teratogens and carcinogens in animals and classified as probable (group 2A) and possible (group 2B) carcinogens in humans by the IARC. High levels of VNAs have been detected in tobacco products and in both mainstream and sidestream smoke. VNA exposure may lead to lipid peroxidation and oxidative stress (e.g., inflammation), chronic diseases (e.g., diabetes) and neurodegenerative diseases (e.g., Alzheimer's disease). To conduct epidemiological studies on the effects of VNA exposure, short-term and long-term stabilities of VNAs in the urine matrix are needed. In this report, the stability of six VNAs (N-nitrosodimethylamine, N-nitrosomethylethylamine, N nitrosodiethylamine, N-nitrosopiperidine, N-nitrosopyrrolidine and N nitrosomorpholine) in human urine is analyzed for the first time using in vitro blank urine pools fortified with a standard mixture of all six VNAs. Over a 24 day period, analytes were monitored in samples stored at ~20 degrees C (collection temperature), 4-10 degrees C (transit temperature) and -20 and -70 degrees C (long-term storage temperatures). All six analytes were stable for 24 days at all temperatures (n = 15). The analytes were then analyzed over a longer time period at -70 degrees C; all analytes were stable for up to 1 year (n = 62). A subset of 44 samples was prepared as a single batch and stored at -20 degrees C, the temperature at which prepared samples are stored. These prepared samples were run in duplicate weekly over 10 weeks, and all six analytes were stable over the entire period (n = 22). PMID- 27274027 TI - Seminal Plasma Promotes Neisseria gonorrhoeae Aggregation and Biofilm Formation. AB - Neisseria gonorrhoeae causes the human-specific disease gonorrhea and is transmitted from person to person primarily via sexual contact. During transmission, N. gonorrhoeae is often exposed to seminal fluid and must adapt to this change in environment. Previous work demonstrated that seminal fluid facilitates N. gonorrhoeae motility and alters epithelial cell interactions. In this study, exposure to seminal fluid was found to decrease surface adherence of gonococci in a manner that was independent of Opa adhesin proteins or type IV pilus retraction. Semen was also shown to cause dispersal of bacteria that had previously established surface adherence. Although surface adherence decreased, interbacterial interactions were increased by seminal plasma both in long-term static culture and on a cell-to-cell basis over shorter time periods. The result of increased bacterium-bacterium interactions resulted in the formation of microcolonies, an important step in the N. gonorrhoeae infectious process. Seminal fluid also facilitated increased bacterial aggregation in the form of shear-resistant three-dimensional biofilms. These results emphasize the importance of the gonococcal response to the influx of seminal fluid within the genital niche. Further characterization of the N. gonorrhoeae response to semen will advance our understanding of the mechanisms behind the establishment of infection in naive hosts and the process of transmission. IMPORTANCE: N. gonorrhoeae is the causative agent of the globally prevalent sexually transmitted infection gonorrhea. An understudied aspect of this human-adapted pathogen is the change in bacterial physiology that occurs during sexual transmission. N. gonorrhoeae encounters semen when transmitted from host to host, and it is known that, when N. gonorrhoeae is exposed to seminal fluid, alterations in bacterial motility and type IV pilus arrangement occur. This work extends our previous observations on this modulation of gonococcal physiology by seminal fluid and demonstrates that seminal plasma decreases surface adherence, promotes interbacterial interactions, and enhances biofilm formation. PMID- 27274028 TI - The SMUL_1544 Gene Product Governs Norcobamide Biosynthesis in the Tetrachloroethene-Respiring Bacterium Sulfurospirillum multivorans. AB - The tetrachloroethene (PCE)-respiring bacterium Sulfurospirillum multivorans produces a unique cobamide, namely, norpseudo-B12, which, in comparison to other cobamides, e.g., cobalamin and pseudo-B12, lacks the methyl group in the linker moiety of the nucleotide loop. In this study, the protein SMUL_1544 was shown to be responsible for the formation of the unusual linker moiety, which is most probably derived from ethanolamine-phosphate (EA-P) as the precursor. The product of the SMUL_1544 gene successfully complemented a Salmonella enterica DeltacobD mutant. The cobD gene encodes an l-threonine-O-3-phosphate (l-Thr-P) decarboxylase responsible for the synthesis of (R)-1-aminopropan-2-ol O-2 phosphate (AP-P), required specifically for cobamide biosynthesis. When SMUL_1544 was produced in the heterologous host lacking CobD, norpseudo-B12 was formed, which pointed toward the formation of EA-P rather than AP-P. Guided cobamide biosynthesis experiments with minimal medium supplemented with l-Thr-P supported cobamide biosynthesis in S. enterica producing SMUL_1544 or S. multivorans Under these conditions, both microorganisms synthesized pseudo-B12 This observation indicated a flexibility in the SMUL_1544 substrate spectrum. From the formation of catalytically active PCE reductive dehalogenase (PceA) in S. multivorans cells producing pseudo-B12, a compatibility of the respiratory enzyme with the cofactor was deduced. This result might indicate a structural flexibility of PceA in cobamide binding. Feeding of l-[3-(13)C]serine to cultures of S. multivorans resulted in isotope labeling of the norpseudo-B12 linker moiety, which strongly supports the hypothesis of EA-P formation from l-serine-O-phosphate (l-Ser-P) in this organism. IMPORTANCE: The identification of the gene product SMUL_1544 as a putative l-Ser-P decarboxylase involved in norcobamide biosynthesis in S. multivorans adds a novel module to the assembly line of cobamides (complete corrinoids) in prokaryotes. Selected cobamide-containing enzymes (e.g., reductive dehalogenases) showed specificity for their cobamide cofactors. It has recently been proposed that the structure of the linker moiety of norpseudo-B12 and the mode of binding of the EA-P linker to the PceA enzyme reflect the high specificity of the enzyme for its cofactor. Data reported herein do not support this idea. In fact, norpseudo-B12 was functional in the cobamide-dependent methionine biosynthesis of S. enterica, raising questions about the role of norcobamides in nature. PMID- 27274029 TI - Essential Genes Predicted in the Genome of Rubrivivax gelatinosus. AB - Rubrivivax gelatinosus is a betaproteobacterium with impressive metabolic diversity. It is capable of phototrophy, chemotrophy, two different mechanisms of sugar metabolism, fermentation, and H2 gas production. To identify core essential genes, R. gelatinosus was subjected to saturating transposon mutagenesis and high throughput sequencing (TnSeq) analysis using nutrient-rich, aerobic conditions. Results revealed that virtually no primary metabolic genes are essential to the organism and that genomic redundancy only explains a portion of the nonessentiality, but some biosynthetic pathways are still essential under nutrient-rich conditions. Different essentialities of different portions of the Pho regulatory pathway suggest that overexpression of the regulon is toxic and hint at a larger connection between phosphate regulation and cellular health. Lastly, various essentialities of different tRNAs hint at a more complex situation than would be expected for such a core process. These results expand upon research regarding cross-organism gene essentiality and further enrich the study of purple nonsulfur bacteria. IMPORTANCE: Microbial genomic data are increasing at a tremendous rate, but physiological characterization of those data lags far behind. One mechanism of high-throughput physiological characterization is TnSeq, which uses high-volume transposon mutagenesis and high-throughput sequencing to identify all of the essential genes in a given organism's genome. Here TnSeq was used to identify essential genes in the metabolically versatile betaproteobacterium Rubrivivax gelatinosus The results presented here add to the growing TnSeq field and also reveal important aspects of R. gelatinosus physiology, which are applicable to researchers working on metabolically flexible organisms. PMID- 27274030 TI - Transcription of Sialic Acid Catabolism Genes in Corynebacterium glutamicum Is Subject to Catabolite Repression and Control by the Transcriptional Repressor NanR. AB - Corynebacterium glutamicum metabolizes sialic acid (Neu5Ac) to fructose-6 phosphate (fructose-6P) via the consecutive activity of the sialic acid importer SiaEFGI, N-acetylneuraminic acid lyase (NanA), N-acetylmannosamine kinase (NanK), N-acetylmannosamine-6P epimerase (NanE), N-acetylglucosamine-6P deacetylase (NagA), and glucosamine-6P deaminase (NagB). Within the cluster of the three operons nagAB, nanAKE, and siaEFGI for Neu5Ac utilization a fourth operon is present, which comprises cg2936, encoding a GntR-type transcriptional regulator, here named NanR. Microarray studies and reporter gene assays showed that nagAB, nanAKE, siaEFGI, and nanR are repressed in wild-type (WT) C. glutamicum but highly induced in a DeltananR C. glutamicum mutant. Purified NanR was found to specifically bind to the nucleotide motifs A[AC]G[CT][AC]TGATGTC[AT][TG]ATGT[AC]TA located within the nagA-nanA and nanR sialA intergenic regions. Binding of NanR to promoter regions was abolished in the presence of the Neu5Ac metabolism intermediates GlcNAc-6P and N acetylmannosamine-6-phosphate (ManNAc-6P). We observed consecutive utilization of glucose and Neu5Ac as well as fructose and Neu5Ac by WT C. glutamicum, whereas the deletion mutant C. glutamicum DeltananR simultaneously consumed these sugars. Increased reporter gene activities for nagAB, nanAKE, and nanR were observed in cultivations of WT C. glutamicum with Neu5Ac as the sole substrate compared to cultivations when fructose was present. Taken together, our findings show that Neu5Ac metabolism in C. glutamicum is subject to catabolite repression, which involves control by the repressor NanR. IMPORTANCE: Neu5Ac utilization is currently regarded as a common trait of both pathogenic and commensal bacteria. Interestingly, the nonpathogenic soil bacterium C. glutamicum efficiently utilizes Neu5Ac as a substrate for growth. Expression of genes for Neu5Ac utilization in C. glutamicum is here shown to depend on the transcriptional regulator NanR, which is the first GntR-type regulator of Neu5Ac metabolism not to use Neu5Ac as effector but relies instead on the inducers GlcNAc-6P and ManNAc 6P. The identification of conserved NanR-binding sites in intergenic regions within the operons for Neu5Ac utilization in pathogenic Corynebacterium species indicates that the mechanism for the control of Neu5Ac catabolism in C. glutamicum by NanR as described in this work is probably conserved within this genus. PMID- 27274031 TI - Genetic and Transcriptional Analyses of the Flagellar Gene Cluster in Actinoplanes missouriensis. AB - Actinoplanes missouriensis, a Gram-positive and soil-inhabiting bacterium, is a member of the rare actinomycetes. The filamentous cells produce sporangia, which contain hundreds of flagellated spores that can swim rapidly for a short period of time until they find niches for germination. These swimming cells are called zoospores, and the mechanism of this unique temporal flagellation has not been elucidated. Here, we report all of the flagellar genes in the bacterial genome and their expected function and contribution for flagellar morphogenesis. We identified a large flagellar gene cluster composed of 33 genes that encode the majority of proteins essential for assembling the functional flagella of Gram positive bacteria. One noted exception to the cluster was the location of the fliQ gene, which was separated from the cluster. We examined the involvement of four genes in flagellar biosynthesis by gene disruption, fliQ, fliC, fliK, and lytA Furthermore, we performed a transcriptional analysis of the flagellar genes using RNA samples prepared from A. missouriensis grown on a sporangium-producing agar medium for 1, 3, 6, and 40 days. We demonstrated that the transcription of the flagellar genes was activated in conjunction with sporangium formation. Eleven transcriptional start points of the flagellar genes were determined using the rapid amplification of cDNA 5' ends (RACE) procedure, which revealed the highly conserved promoter sequence CTCA(N15-17)GCCGAA. This result suggests that a sigma factor is responsible for the transcription of all flagellar genes and that the flagellar structure assembles simultaneously. IMPORTANCE: The biology of a zoospore is very interesting from the viewpoint of morphogenesis, survival strategy, and evolution. Here, we analyzed flagellar genes in A. missouriensis, which produces sporangia containing hundreds of flagellated spores each. Zoospores released from the sporangia swim for a short time before germination occurs. We identified a large flagellar gene cluster and an orphan flagellar gene (fliQ). These findings indicate that the zoospore flagellar components are typical of Gram-positive bacteria. However, the transcriptional analysis revealed that all flagellar genes are transcribed simultaneously during sporangium formation, a pattern differing from the orderly, regulated expression of flagellar genes in other bacteria, such as Salmonella and Escherichia coli These results suggest a novel regulatory mechanism for flagellar formation in A. missouriensis. PMID- 27274034 TI - Science and Culture: How fish innards inspire art. PMID- 27274032 TI - Microfluidic Studies of Biofilm Formation in Dynamic Environments. AB - The advent of microscale technologies, such as microfluidics, has revolutionized many areas of biology yet has only recently begun to impact the field of bacterial biofilms. By enabling accurate control and manipulation of physical and chemical conditions, these new microscale approaches afford the ability to combine important features of natural and artificial microbial habitats, such as fluid flow and ephemeral nutrient sources, with an unprecedented level of flexibility and quantification. Here, we review selected case studies to exemplify this potential, discuss limitations, and suggest that this approach opens new vistas into biofilm research over traditional setups, allowing us to expand our understanding of the formation and consequences of biofilms in a broad range of environments and applications. PMID- 27274035 TI - Core Concept: Are we in the "Anthropocene"? PMID- 27274038 TI - Opinion: Big data biomedicine offers big higher education opportunities. PMID- 27274040 TI - Issues in human evolution. PMID- 27274041 TI - Unraveling the evolution of uniquely human cognition. AB - A satisfactory account of human cognitive evolution will explain not only the psychological mechanisms that make our species unique, but also how, when, and why these traits evolved. To date, researchers have made substantial progress toward defining uniquely human aspects of cognition, but considerably less effort has been devoted to questions about the evolutionary processes through which these traits have arisen. In this article, I aim to link these complementary aims by synthesizing recent advances in our understanding of what makes human cognition unique, with theory and data regarding the processes of cognitive evolution. I review evidence that uniquely human cognition depends on synergism between both representational and motivational factors and is unlikely to be accounted for by changes to any singular cognitive system. I argue that, whereas no nonhuman animal possesses the full constellation of traits that define the human mind, homologies and analogies of critical aspects of human psychology can be found in diverse nonhuman taxa. I suggest that phylogenetic approaches to the study of animal cognition-which can address questions about the selective pressures and proximate mechanisms driving cognitive change-have the potential to yield important insights regarding the processes through which the human cognitive phenotype evolved. PMID- 27274042 TI - Neogene biomarker record of vegetation change in eastern Africa. AB - The evolution of C4 grassland ecosystems in eastern Africa has been intensely studied because of the potential influence of vegetation on mammalian evolution, including that of our own lineage, hominins. Although a handful of sparse vegetation records exists from middle and early Miocene terrestrial fossil sites, there is no comprehensive record of vegetation through the Neogene. Here we present a vegetation record spanning the Neogene and Quaternary Periods that documents the appearance and subsequent expansion of C4 grasslands in eastern Africa. Carbon isotope ratios from terrestrial plant wax biomarkers deposited in marine sediments indicate constant C3 vegetation from ~24 Ma to 10 Ma, when C4 grasses first appeared. From this time forward, C4 vegetation increases monotonically to present, with a coherent signal between marine core sites located in the Somali Basin and the Red Sea. The response of mammalian herbivores to the appearance of C4 grasses at 10 Ma is immediate, as evidenced from existing records of mammalian diets from isotopic analyses of tooth enamel. The expansion of C4 vegetation in eastern Africa is broadly mirrored by increasing proportions of C4-based foods in hominin diets, beginning at 3.8 Ma in Australopithecus and, slightly later, Kenyanthropus This continues into the late Pleistocene in Paranthropus, whereas Homo maintains a flexible diet. The biomarker vegetation record suggests the increase in open, C4 grassland ecosystems over the last 10 Ma may have operated as a selection pressure for traits and behaviors in Homo such as bipedalism, flexible diets, and complex social structure. PMID- 27274043 TI - The Pliocene hominin diversity conundrum: Do more fossils mean less clarity? AB - Recent discoveries of multiple middle Pliocene hominins have raised the possibility that early hominins were as speciose as later hominins. However, debates continue to arise around the validity of most of these new taxa, largely based on poor preservation of holotype specimens, small sample size, or the lack of evidence for ecological diversity. A closer look at the currently available fossil evidence from Ethiopia, Kenya, and Chad indicate that Australopithecus afarensis was not the only hominin species during the middle Pliocene, and that there were other species clearly distinguishable from it by their locomotor adaptation and diet. Although there is no doubt that the presence of multiple species during the middle Pliocene opens new windows into our evolutionary past, it also complicates our understanding of early hominin taxonomy and phylogenetic relationships. PMID- 27274044 TI - Neandertals revised. AB - The last decade has seen a significant growth of our knowledge of the Neandertals, a population of Pleistocene hunter-gatherers who lived in (western) Eurasia between ~400,000 and 40,000 y ago. Starting from a source population deep in the Middle Pleistocene, the hundreds of thousands of years of relative separation between African and Eurasian groups led to the emergence of different phenotypes in Late Pleistocene Europe and Africa. Both recently obtained genetic evidence and archeological data show that the biological and cultural gaps between these populations were probably smaller than previously thought. These data, reviewed here, falsify inferences to the effect that, compared with their near-modern contemporaries in Africa, Neandertals were outliers in terms of behavioral complexity. It is only around 40,000 y ago, tens of thousands of years after anatomically modern humans first left Africa and thousands of years after documented interbreeding between modern humans, Neandertals and Denisovans, that we see major changes in the archeological record, from western Eurasia to Southeast Asia, e.g., the emergence of representational imagery and the colonization of arctic areas and of greater Australia (Sahul). PMID- 27274045 TI - Ancient DNA and human history. AB - We review studies of genomic data obtained by sequencing hominin fossils with particular emphasis on the unique information that ancient DNA (aDNA) can provide about the demographic history of humans and our closest relatives. We concentrate on nuclear genomic sequences that have been published in the past few years. In many cases, particularly in the Arctic, the Americas, and Europe, aDNA has revealed historical demographic patterns in a way that could not be resolved by analyzing present-day genomes alone. Ancient DNA from archaic hominins has revealed a rich history of admixture between early modern humans, Neanderthals, and Denisovans, and has allowed us to disentangle complex selective processes. Information from aDNA studies is nowhere near saturation, and we believe that future aDNA sequences will continue to change our understanding of hominin history. PMID- 27274046 TI - Ecological consequences of human niche construction: Examining long-term anthropogenic shaping of global species distributions. AB - The exhibition of increasingly intensive and complex niche construction behaviors through time is a key feature of human evolution, culminating in the advanced capacity for ecosystem engineering exhibited by Homo sapiens A crucial outcome of such behaviors has been the dramatic reshaping of the global biosphere, a transformation whose early origins are increasingly apparent from cumulative archaeological and paleoecological datasets. Such data suggest that, by the Late Pleistocene, humans had begun to engage in activities that have led to alterations in the distributions of a vast array of species across most, if not all, taxonomic groups. Changes to biodiversity have included extinctions, extirpations, and shifts in species composition, diversity, and community structure. We outline key examples of these changes, highlighting findings from the study of new datasets, like ancient DNA (aDNA), stable isotopes, and microfossils, as well as the application of new statistical and computational methods to datasets that have accumulated significantly in recent decades. We focus on four major phases that witnessed broad anthropogenic alterations to biodiversity-the Late Pleistocene global human expansion, the Neolithic spread of agriculture, the era of island colonization, and the emergence of early urbanized societies and commercial networks. Archaeological evidence documents millennia of anthropogenic transformations that have created novel ecosystems around the world. This record has implications for ecological and evolutionary research, conservation strategies, and the maintenance of ecosystem services, pointing to a significant need for broader cross-disciplinary engagement between archaeology and the biological and environmental sciences. PMID- 27274047 TI - IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction. AB - Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF 1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in postischemic heart disease. PMID- 27274048 TI - Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies. AB - The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. Here, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Using this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS-specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens. PMID- 27274049 TI - Early farmers from across Europe directly descended from Neolithic Aegeans. AB - Farming and sedentism first appeared in southwestern Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion, and admixture with local foragers in the early Neolithization of Europe. Here we present paleogenomic data for five Neolithic individuals from northern Greece and northwestern Turkey spanning the time and region of the earliest spread of farming into Europe. We use a novel approach to recalibrate raw reads and call genotypes from ancient DNA and observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia. PMID- 27274050 TI - Scaling identity connects human mobility and social interactions. AB - Massive datasets that capture human movements and social interactions have catalyzed rapid advances in our quantitative understanding of human behavior during the past years. One important aspect affecting both areas is the critical role space plays. Indeed, growing evidence suggests both our movements and communication patterns are associated with spatial costs that follow reproducible scaling laws, each characterized by its specific critical exponents. Although human mobility and social networks develop concomitantly as two prolific yet largely separated fields, we lack any known relationships between the critical exponents explored by them, despite the fact that they often study the same datasets. Here, by exploiting three different mobile phone datasets that capture simultaneously these two aspects, we discovered a new scaling relationship, mediated by a universal flux distribution, which links the critical exponents characterizing the spatial dependencies in human mobility and social networks. Therefore, the widely studied scaling laws uncovered in these two areas are not independent but connected through a deeper underlying reality. PMID- 27274051 TI - Bison phylogeography constrains dispersal and viability of the Ice Free Corridor in western Canada. AB - The Ice Free Corridor has been invoked as a route for Pleistocene human and animal dispersals between eastern Beringia and more southerly areas of North America. Despite the significance of the corridor, there are limited data for when and how this corridor was used. Hypothetical uses of the corridor include: the first expansion of humans from Beringia into the Americas, northward postglacial expansions of fluted point technologies into Beringia, and continued use of the corridor as a contact route between the north and south. Here, we use radiocarbon dates and ancient mitochondrial DNA from late Pleistocene bison fossils to determine the chronology for when the corridor was open and viable for biotic dispersals. The corridor was closed after ~23,000 until 13,400 calendar years ago (cal y BP), after which we find the first evidence, to our knowledge, that bison used this route to disperse from the south, and by 13,000 y from the north. Our chronology supports a habitable and traversable corridor by at least 13,000 cal y BP, just before the first appearance of Clovis technology in interior North America, and indicates that the corridor would not have been available for significantly earlier southward human dispersal. Following the opening of the corridor, multiple dispersals of human groups between Beringia and interior North America may have continued throughout the latest Pleistocene and early Holocene. Our results highlight the utility of phylogeographic analyses to test hypotheses about paleoecological history and the viability of dispersal routes over time. PMID- 27274052 TI - PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. AB - Prostate cancer has the second highest incidence among cancers in men worldwide and is the second leading cause of cancer deaths of men in the United States. Although androgen deprivation can initially lead to remission, the disease often progresses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR) signaling and is associated with a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance invariably emerges, and new therapies are urgently needed. Recently, inhibitors of bromodomain and extra-terminal (BET) family proteins have shown growth-inhibitory activity in preclinical models of CRPC. Here, we demonstrate that ARV-771, a small-molecule pan-BET degrader based on proteolysis targeting chimera (PROTAC) technology, demonstrates dramatically improved efficacy in cellular models of CRPC as compared with BET inhibition. Unlike BET inhibitors, ARV-771 results in suppression of both AR signaling and AR levels and leads to tumor regression in a CRPC mouse xenograft model. This study is, to our knowledge, the first to demonstrate efficacy with a small-molecule BET degrader in a solid-tumor malignancy and potentially represents an important therapeutic advance in the treatment of CRPC. PMID- 27274053 TI - A scalable strategy for high-throughput GFP tagging of endogenous human proteins. AB - A central challenge of the postgenomic era is to comprehensively characterize the cellular role of the ~20,000 proteins encoded in the human genome. To systematically study protein function in a native cellular background, libraries of human cell lines expressing proteins tagged with a functional sequence at their endogenous loci would be very valuable. Here, using electroporation of Cas9 nuclease/single-guide RNA ribonucleoproteins and taking advantage of a split-GFP system, we describe a scalable method for the robust, scarless, and specific tagging of endogenous human genes with GFP. Our approach requires no molecular cloning and allows a large number of cell lines to be processed in parallel. We demonstrate the scalability of our method by targeting 48 human genes and show that the resulting GFP fluorescence correlates with protein expression levels. We next present how our protocols can be easily adapted for the tagging of a given target with GFP repeats, critically enabling the study of low-abundance proteins. Finally, we show that our GFP tagging approach allows the biochemical isolation of native protein complexes for proteomic studies. Taken together, our results pave the way for the large-scale generation of endogenously tagged human cell lines for the proteome-wide analysis of protein localization and interaction networks in a native cellular context. PMID- 27274054 TI - GEFs and Rac GTPases control directional specificity of neurite extension along the anterior-posterior axis. AB - Although previous studies have identified many extracellular guidance molecules and intracellular signaling proteins that regulate axonal outgrowth and extension, most were conducted in the context of unidirectional neurite growth, in which the guidance cues either attract or repel growth cones. Very few studies addressed how intracellular signaling molecules differentially specify bidirectional outgrowth. Here, using the bipolar PLM neurons in Caenorhabditis elegans, we show that the guanine nucleotide exchange factors (GEFs) UNC-73/Trio and TIAM-1 promote anterior and posterior neurite extension, respectively. The Rac subfamily GTPases act downstream of the GEFs; CED-10/Rac1 is activated by TIAM-1, whereas CED-10 and MIG-2/RhoG act redundantly downstream of UNC-73. Moreover, these two pathways antagonize each other and thus regulate the directional bias of neuritogenesis. Our study suggests that directional specificity of neurite extension is conferred through the intracellular activation of distinct GEFs and Rac GTPases. PMID- 27274055 TI - Ancient mtDNA sequences from the First Australians revisited. AB - The publication in 2001 by Adcock et al. [Adcock GJ, et al. (2001) Proc Natl Acad Sci USA 98(2):537-542] in PNAS reported the recovery of short mtDNA sequences from ancient Australians, including the 42,000-y-old Mungo Man [Willandra Lakes Hominid (WLH3)]. This landmark study in human ancient DNA suggested that an early modern human mitochondrial lineage emerged in Asia and that the theory of modern human origins could no longer be considered solely through the lens of the "Out of Africa" model. To evaluate these claims, we used second generation DNA sequencing and capture methods as well as PCR-based and single-primer extension (SPEX) approaches to reexamine the same four Willandra Lakes and Kow Swamp 8 (KS8) remains studied in the work by Adcock et al. Two of the remains sampled contained no identifiable human DNA (WLH15 and WLH55), whereas the Mungo Man (WLH3) sample contained no Aboriginal Australian DNA. KS8 reveals human mitochondrial sequences that differ from the previously inferred sequence. Instead, we recover a total of five modern European contaminants from Mungo Man (WLH3). We show that the remaining sample (WLH4) contains ~1.4% human DNA, from which we assembled two complete mitochondrial genomes. One of these was a previously unidentified Aboriginal Australian haplotype belonging to haplogroup S2 that we sequenced to a high coverage. The other was a contaminating modern European mitochondrial haplotype. Although none of the sequences that we recovered matched those reported by Adcock et al., except a contaminant, these findings show the feasibility of obtaining important information from ancient Aboriginal Australian remains. PMID- 27274056 TI - Leucokinin mimetic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron. AB - Insect kinins (leucokinins) are multifunctional peptides acting as neurohormones and neurotransmitters. In females of the mosquito vector Aedes aegypti (L.), aedeskinins are known to stimulate fluid secretion from the renal organs (Malpighian tubules) and hindgut contractions by activating a G protein-coupled kinin receptor designated "Aedae-KR." We used protease-resistant kinin analogs 1728, 1729, and 1460 to evaluate their effects on sucrose perception and feeding behavior. In no-choice feeding bioassays (capillary feeder and plate assays), the analog 1728, which contains alpha-amino isobutyric acid, inhibited females from feeding on sucrose. It further induced quick fly-away or walk-away behavior following contact with the tarsi and the mouthparts. Electrophysiological recordings from single long labellar sensilla of the proboscis demonstrated that mixing the analog 1728 at 1 mM with sucrose almost completely inhibited the detection of sucrose. Aedae-KR was immunolocalized in contact chemosensory neurons in prothoracic tarsi and in sensory neurons and accessory cells of long labellar sensilla in the distal labellum. Silencing Aedae-KR by RNAi significantly reduced gene expression and eliminated the feeding-aversion behavior resulting from contact with the analog 1728, thus directly implicating the Aedae-KR in the aversion response. To our knowledge, this is the first report that kinin analogs modulate sucrose perception in any insect. The aversion to feeding elicited by analog 1728 suggests that synthetic molecules targeting the mosquito Aedae-KR in the labellum and tarsi should be investigated for the potential to discover novel feeding deterrents of mosquito vectors. PMID- 27274058 TI - Encounter with mesoscale eddies enhances survival to settlement in larval coral reef fishes. AB - Oceanographic features, such as eddies and fronts, enhance and concentrate productivity, generating high-quality patches that dispersive marine larvae may encounter in the plankton. Although broad-scale movement of larvae associated with these features can be captured in biophysical models, direct evidence of processes influencing survival within them, and subsequent effects on population replenishment, are unknown. We sequentially sampled cohorts of coral reef fishes in the plankton and nearshore juvenile habitats in the Straits of Florida and used otolith microstructure analysis to compare growth and size-at-age of larvae collected inside and outside of mesoscale eddies to those that survived to settlement. Larval habitat altered patterns of growth and selective mortality: Thalassoma bifasciatum and Cryptotomus roseus that encountered eddies in the plankton grew faster than larvae outside of eddies and likely experienced higher survival to settlement. During warm periods, T. bifasciatum residing outside of eddies in the oligotrophic Florida Current experienced high mortality and only the slowest growers survived early larval life. Such slow growth is advantageous in nutrient poor habitats when warm temperatures increase metabolic demands but is insufficient for survival beyond the larval stage because only fast-growing larvae successfully settled to reefs. Because larvae arriving to the Straits of Florida from distant sources must spend long periods of time outside of eddies, our results indicate that they have a survival disadvantage. High productivity features such as eddies not only enhance the survival of pelagic larvae, but also potentially increase the contribution of locally spawned larvae to reef populations. PMID- 27274057 TI - Musashi-2 (MSI2) supports TGF-beta signaling and inhibits claudins to promote non small cell lung cancer (NSCLC) metastasis. AB - Non-small cell lung cancer (NSCLC) has a 5-y survival rate of ~16%, with most deaths associated with uncontrolled metastasis. We screened for stem cell identity-related genes preferentially expressed in a panel of cell lines with high versus low metastatic potential, derived from NSCLC tumors of Kras(LA1/+);P53(R172HDeltaG/+) (KP) mice. The Musashi-2 (MSI2) protein, a regulator of mRNA translation, was consistently elevated in metastasis-competent cell lines. MSI2 was overexpressed in 123 human NSCLC tumor specimens versus normal lung, whereas higher expression was associated with disease progression in an independent set of matched normal/primary tumor/lymph node specimens. Depletion of MSI2 in multiple independent metastatic murine and human NSCLC cell lines reduced invasion and metastatic potential, independent of an effect on proliferation. MSI2 depletion significantly induced expression of proteins associated with epithelial identity, including tight junction proteins [claudin 3 (CLDN3), claudin 5 (CLDN5), and claudin 7 (CLDN7)] and down-regulated direct translational targets associated with epithelial-mesenchymal transition, including the TGF-beta receptor 1 (TGFbetaR1), the small mothers against decapentaplegic homolog 3 (SMAD3), and the zinc finger proteins SNAI1 (SNAIL) and SNAI2 (SLUG). Overexpression of TGFbetaRI reversed the loss of invasion associated with MSI2 depletion, whereas overexpression of CLDN7 inhibited MSI2 dependent invasion. Unexpectedly, MSI2 depletion reduced E-cadherin expression, reflecting a mixed epithelial-mesenchymal phenotype. Based on this work, we propose that MSI2 provides essential support for TGFbetaR1/SMAD3 signaling and contributes to invasive adenocarcinoma of the lung and may serve as a predictive biomarker of NSCLC aggressiveness. PMID- 27274059 TI - Chiral modes and directional lasing at exceptional points. AB - Controlling the emission and the flow of light in micro- and nanostructures is crucial for on-chip information processing. Here we show how to impose a strong chirality and a switchable direction of light propagation in an optical system by steering it to an exceptional point (EP)-a degeneracy universally occurring in all open physical systems when two eigenvalues and the corresponding eigenstates coalesce. In our experiments with a fiber-coupled whispering-gallery-mode (WGM) resonator, we dynamically control the chirality of resonator modes and the emission direction of a WGM microlaser in the vicinity of an EP: Away from the EPs, the resonator modes are nonchiral and laser emission is bidirectional. As the system approaches an EP, the modes become chiral and allow unidirectional emission such that by transiting from one EP to another one the direction of emission can be completely reversed. Our results exemplify a very counterintuitive feature of non-Hermitian physics that paves the way to chiral photonics on a chip. PMID- 27274060 TI - Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo. AB - Glaucoma is a common cause of vision loss or blindness and reduction of intraocular pressure (IOP) has been proven beneficial in a large fraction of glaucoma patients. The IOP is maintained by the trabecular meshwork (TM) and the elevation of IOP in open-angle glaucoma is associated with dysfunction and loss of the postmitotic cells residing within this tissue. To determine if IOP control can be maintained by replacing lost TM cells, we transplanted TM-like cells derived from induced pluripotent stem cells into the anterior chamber of a transgenic mouse model of glaucoma. Transplantation led to significantly reduced IOP and improved aqueous humor outflow facility, which was sustained for at least 9 wk. The ability to maintain normal IOP engendered survival of retinal ganglion cells, whose loss is ultimately the cause for reduced vision in glaucoma. In vivo and in vitro analyses demonstrated higher TM cellularity in treated mice compared with littermate controls and indicated that this increase is primarily because of a proliferative response of endogenous TM cells. Thus, our study provides in vivo demonstration that regeneration of the glaucomatous TM is possible and points toward novel approaches in the treatment of this disease. PMID- 27274061 TI - Southern Ocean phytoplankton turnover in response to stepwise Antarctic cooling over the past 15 million years. AB - It is not clear how Southern Ocean phytoplankton communities, which form the base of the marine food web and are a crucial element of the carbon cycle, respond to major environmental disturbance. Here, we use a new model ensemble reconstruction of diatom speciation and extinction rates to examine phytoplankton response to climate change in the southern high latitudes over the past 15 My. We identify five major episodes of species turnover (origination rate plus extinction rate) that were coincident with times of cooling in southern high-latitude climate, Antarctic ice sheet growth across the continental shelves, and associated seasonal sea-ice expansion across the Southern Ocean. We infer that past plankton turnover occurred when a warmer-than-present climate was terminated by a major period of glaciation that resulted in loss of open-ocean habitat south of the polar front, driving non-ice adapted diatoms to regional or global extinction. These findings suggest, therefore, that Southern Ocean phytoplankton communities tolerate "baseline" variability on glacial-interglacial timescales but are sensitive to large-scale changes in mean climate state driven by a combination of long-period variations in orbital forcing and atmospheric carbon dioxide perturbations. PMID- 27274062 TI - A class II KNOX gene, KNOX4, controls seed physical dormancy. AB - Physical dormancy of seed is an adaptive trait that widely exists in higher plants. This kind of dormancy is caused by a water-impermeable layer that blocks water and oxygen from the surrounding environment and keeps embryos in a viable status for a long time. Most of the work on hardseededness has focused on morphological structure and phenolic content of seed coat. The molecular mechanism underlying physical dormancy remains largely elusive. By screening a large number of Tnt1 retrotransposon-tagged Medicago truncatula lines, we identified nondormant seed mutants from this model legume species. Unlike wild type hard seeds exhibiting physical dormancy, the mature mutant seeds imbibed water quickly and germinated easily, without the need for scarification. Microscopic observations of cross sections showed that the mutant phenotype was caused by a dysfunctional palisade cuticle layer in the seed coat. Chemical analysis found differences in lipid monomer composition between the wild-type and mutant seed coats. Genetic and molecular analyses revealed that a class II KNOTTED-like homeobox (KNOXII) gene, KNOX4, was responsible for the loss of physical dormancy in the seeds of the mutants. Microarray and chromatin immunoprecipitation analyses identified CYP86A, a gene associated with cutin biosynthesis, as one of the downstream target genes of KNOX4 This study elucidated a novel molecular mechanism of physical dormancy and revealed a new role of class II KNOX genes. Furthermore, KNOX4-like genes exist widely in seed plants but are lacking in nonseed species, indicating that KNOX4 may have diverged from the other KNOXII genes during the evolution of seed plants. PMID- 27274064 TI - Role of quasiresonant planetary wave dynamics in recent boreal spring-to-autumn extreme events. AB - In boreal spring-to-autumn (May-to-September) 2012 and 2013, the Northern Hemisphere (NH) has experienced a large number of severe midlatitude regional weather extremes. Here we show that a considerable part of these extremes were accompanied by highly magnified quasistationary midlatitude planetary waves with zonal wave numbers m = 6, 7, and 8. We further show that resonance conditions for these planetary waves were, in many cases, present before the onset of high amplitude wave events, with a lead time up to 2 wk, suggesting that quasiresonant amplification (QRA) of these waves had occurred. Our results support earlier findings of an important role of the QRA mechanism in amplifying planetary waves, favoring recent NH weather extremes. PMID- 27274063 TI - APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury. AB - A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury. PMID- 27274065 TI - DEG9, a serine protease, modulates cytokinin and light signaling by regulating the level of ARABIDOPSIS RESPONSE REGULATOR 4. AB - Cytokinin is an essential phytohormone that controls various biological processes in plants. A number of response regulators are known to be important for cytokinin signal transduction. ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4) mediates the cross-talk between light and cytokinin signaling through modulation of the activity of phytochrome B. However, the mechanism that regulates the activity and stability of ARR4 is unknown. Here we identify an ATP-independent serine protease, degradation of periplasmic proteins 9 (DEG9), which localizes to the nucleus and regulates the stability of ARR4. Biochemical evidence shows that DEG9 interacts with ARR4, thereby targeting ARR4 for degradation, which suggests that DEG9 regulates the stability of ARR4. Moreover, genetic evidence shows that DEG9 acts upstream of ARR4 and regulates the activity of ARR4 in cytokinin and light signaling pathways. This study thus identifies a role for a ubiquitin-independent selective protein proteolysis in the regulation of the stability of plant signaling components. PMID- 27274067 TI - Coherent two-dimensional terahertz-terahertz-Raman spectroscopy. AB - We present 2D terahertz-terahertz-Raman (2D TTR) spectroscopy, the first technique, to our knowledge, to interrogate a liquid with multiple pulses of terahertz (THz) light. This hybrid approach isolates nonlinear signatures in isotropic media, and is sensitive to the coupling and anharmonicity of thermally activated THz modes that play a central role in liquid-phase chemistry. Specifically, by varying the timing between two intense THz pulses, we control the orientational alignment of molecules in a liquid, and nonlinearly excite vibrational coherences. A comparison of experimental and simulated 2D TTR spectra of bromoform (CHBr3), carbon tetrachloride (CCl4), and dibromodichloromethane (CBr2Cl2) shows previously unobserved off-diagonal anharmonic coupling between thermally populated vibrational modes. PMID- 27274066 TI - Tau protein is essential for stress-induced brain pathology. AB - Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function. PMID- 27274068 TI - Photodegradation of retinal bisretinoids in mouse models and implications for macular degeneration. AB - Adducts of retinaldehyde (bisretinoids) form nonenzymatically in photoreceptor cells and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin; these fluorophores are implicated in the pathogenesis of inherited and age related macular degeneration (AMD). Here we demonstrate that bisretinoid photodegradation is ongoing in the eye. High-performance liquid chromatography (HPLC) analysis of eyes of dark-reared and cyclic light-reared wild-type mice, together with comparisons of pigmented versus albino mice, revealed a relationship between intraocular light and reduced levels of the bisretinoids A2E and A2-glycero-phosphoethanolamine (A2-GPE). Analysis of the bisretinoids A2E, A2 GPE, A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE), and all-trans retinal dimer-phosphatidylethanolamine (all-trans-retinal dimer-PE) also decreases in albino Abca4(-/-) mice reared in cyclic light compared with darkness. In albino Abca4(-/-) mice receiving a diet supplemented with the antioxidant vitamin E, higher levels of RPE bisretinoid were evidenced by HPLC analysis and quantitation of fundus autofluorescence; this effect is consistent with photooxidative processes known to precede bisretinoid degradation. Amelioration of outer nuclear layer thinning indicated that vitamin E treatment protected photoreceptor cells. Conversely, in-cage exposure to short-wavelength light resulted in reduced fundus autofluorescence, decreased HPLC-quantified A2E, outer nuclear layer thinning, and increased methylglyoxal (MG)-adducted protein. MG was also released upon bisretinoid photodegradation in cells. We suggest that the lower levels of these diretinal adducts in cyclic light-reared and albino mice reflect photodegradative loss of bisretinoid. These mechanisms may underlie associations among AMD risk, oxidative mechanisms, and lifetime light exposure. PMID- 27274069 TI - Overexpression of a pH-sensitive nitrate transporter in rice increases crop yields. AB - Cellular pH homeostasis is fundamental for life, and all cells adapt to maintain this balance. In plants, the chemical form of nitrogen supply, nitrate and ammonium, is one of the cellular pH dominators. We report that the rice nitrate transporter OsNRT2.3 is transcribed into two spliced isoforms with a natural variation in expression ratio. One splice form, OsNRT2.3b is located on the plasma membrane, is expressed mainly in the phloem, and has a regulatory motif on the cytosolic side that acts to switch nitrate transport activity on or off by a pH-sensing mechanism. High OsNRT2.3b expression in rice enhances the pH-buffering capacity of the plant, increasing N, Fe, and P uptake. In field trials, increased expression of OsNRT2.3b improved grain yield and nitrogen use efficiency (NUE) by 40%. These results indicate that pH sensing by the rice nitrate transporter OsNRT2.3b is important for plant adaption to varied N supply forms and can provide a target for improving NUE. PMID- 27274070 TI - Digital design of multimaterial photonic particles. AB - Scattering of light from dielectric particles whose size is on the order of an optical wavelength underlies a plethora of visual phenomena in nature and is a foundation for optical coatings and paints. Tailoring the internal nanoscale geometry of such "photonic particles" allows tuning their optical scattering characteristics beyond those afforded by their constitutive materials-however, flexible yet scalable processing approaches to produce such particles are lacking. Here, we show that a thermally induced in-fiber fluid instability permits the "digital design" of multimaterial photonic particles: the precise allocation of high refractive-index contrast materials at independently addressable radial and azimuthal coordinates within its 3D architecture. Exploiting this unique capability in all-dielectric systems, we tune the scattering cross-section of equisized particles via radial structuring and induce polarization-sensitive scattering from spherical particles with broken internal rotational symmetry. The scalability of this fabrication strategy promises a generation of optical coatings in which sophisticated functionality is realized at the level of the individual particles. PMID- 27274071 TI - Directed vaccination against pneumococcal disease. AB - Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a "smart" vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens. PMID- 27274073 TI - Measurement of background gamma radiation in the northern Marshall Islands. AB - We report measurements of background gamma radiation levels on six islands in the northern Marshall Islands (Enewetak, Medren, and Runit onEnewetak Atoll; Bikini and Nam on Bikini Atoll; and Rongelap on Rongelap Atoll). Measurable excess radiation could be expected from the decay of (137)Cs produced by the US nuclear testing program there from 1946 to 1958. These recordings are of relevance to safety of human habitation and resettlement. We find low levels of gamma radiation for the settled island of Enewetak [mean = 7.6 millirem/year (mrem/y) = 0.076 millisievert/year (mSv/y)], larger levels of gamma radiation for the island of Rongelap (mean = 19.8 mrem/y = 0.198 mSv/y), and relatively high gamma radiation on the island of Bikini (mean = 184 mrem/y = 1.84 mSv/y). Distributions of gamma radiation levels are provided, and hot spots are discussed. We provide interpolated maps for four islands (Enewetak, Medren, Bikini, and Rongelap), and make comparisons to control measurements performed on the island of Majuro in the southern Marshall Islands, measurements made in Central Park in New York City, and the standard agreed upon by the United States and the Republic of the Marshall Islands (RMI) governments (100 mrem/y = 1 mSv/y). External gamma radiation levels on Bikini Island significantly exceed this standard (P = <<0.01), and external gamma radiation levels on the other islands are below the standard. To determine conclusively whether these islands are safe for habitation, radiation exposure through additional pathways such as food ingestion must be considered. PMID- 27274072 TI - Characterizing treatment pathways at scale using the OHDSI network. AB - Observational research promises to complement experimental research by providing large, diverse populations that would be infeasible for an experiment. Observational research can test its own clinical hypotheses, and observational studies also can contribute to the design of experiments and inform the generalizability of experimental research. Understanding the diversity of populations and the variance in care is one component. In this study, the Observational Health Data Sciences and Informatics (OHDSI) collaboration created an international data network with 11 data sources from four countries, including electronic health records and administrative claims data on 250 million patients. All data were mapped to common data standards, patient privacy was maintained by using a distributed model, and results were aggregated centrally. Treatment pathways were elucidated for type 2 diabetes mellitus, hypertension, and depression. The pathways revealed that the world is moving toward more consistent therapy over time across diseases and across locations, but significant heterogeneity remains among sources, pointing to challenges in generalizing clinical trial results. Diabetes favored a single first-line medication, metformin, to a much greater extent than hypertension or depression. About 10% of diabetes and depression patients and almost 25% of hypertension patients followed a treatment pathway that was unique within the cohort. Aside from factors such as sample size and underlying population (academic medical center versus general population), electronic health records data and administrative claims data revealed similar results. Large-scale international observational research is feasible. PMID- 27274074 TI - Leaping eels electrify threats, supporting Humboldt's account of a battle with horses. AB - In March 1800, Alexander von Humboldt observed the extraordinary spectacle of native fisherman collecting electric eels (Electrophorus electricus) by "fishing with horses" [von Humboldt A (1807) Ann Phys 25:34-43]. The strategy was to herd horses into a pool containing electric eels, provoking the eels to attack by pressing themselves against the horses while discharging. Once the eels were exhausted, they could be safely collected. This legendary tale of South American adventures helped propel Humboldt to fame and has been recounted and illustrated in many publications, but subsequent investigators have been skeptical, and no similar eel behavior has been reported in more than 200 years. Here I report a defensive eel behavior that supports Humboldt's account. The behavior consists of an approach and leap out of the water during which the eel presses its chin against a threatening conductor while discharging high-voltage volleys. The effect is to short-circuit the electric organ through the threat, with increasing power diverted to the threat as the eel attains greater height during the leap. Measurement of voltages and current during the behavior, and assessment of the equivalent circuit, reveal the effectiveness of the behavior and the basis for its natural selection. PMID- 27274075 TI - Neural mechanisms underlying the impact of daylong cognitive work on economic decisions. AB - The ability to exert self-control is key to social insertion and professional success. An influential literature in psychology has developed the theory that self-control relies on a limited common resource, so that fatigue effects might carry over from one task to the next. However, the biological nature of the putative limited resource and the existence of carry-over effects have been matters of considerable controversy. Here, we targeted the activity of the lateral prefrontal cortex (LPFC) as a common substrate for cognitive control, and we prolonged the time scale of fatigue induction by an order of magnitude. Participants performed executive control tasks known to recruit the LPFC (working memory and task-switching) over more than 6 h (an approximate workday). Fatigue effects were probed regularly by measuring impulsivity in intertemporal choices, i.e., the propensity to favor immediate rewards, which has been found to increase under LPFC inhibition. Behavioral data showed that choice impulsivity increased in a group of participants who performed hard versions of executive tasks but not in control groups who performed easy versions or enjoyed some leisure time. Functional MRI data acquired at the start, middle, and end of the day confirmed that enhancement of choice impulsivity was related to a specific decrease in the activity of an LPFC region (in the left middle frontal gyrus) that was recruited by both executive and choice tasks. Our findings demonstrate a concept of focused neural fatigue that might be naturally induced in real-life situations and have important repercussions on economic decisions. PMID- 27274077 TI - Nonlinear analogue of the May-Wigner instability transition. AB - We study a system of [Formula: see text] degrees of freedom coupled via a smooth homogeneous Gaussian vector field with both gradient and divergence-free components. In the absence of coupling, the system is exponentially relaxing to an equilibrium with rate MU We show that, while increasing the ratio of the coupling strength to the relaxation rate, the system experiences an abrupt transition from a topologically trivial phase portrait with a single equilibrium into a topologically nontrivial regime characterized by an exponential number of equilibria, the vast majority of which are expected to be unstable. It is suggested that this picture provides a global view on the nature of the May Wigner instability transition originally discovered by local linear stability analysis. PMID- 27274076 TI - Pseudomonas syringae type III effector HopAF1 suppresses plant immunity by targeting methionine recycling to block ethylene induction. AB - HopAF1 is a type III effector protein of unknown function encoded in the genomes of several strains of Pseudomonas syringae and other plant pathogens. Structural modeling predicted that HopAF1 is closely related to deamidase proteins. Deamidation is the irreversible substitution of an amide group with a carboxylate group. Several bacterial virulence factors are deamidases that manipulate the activity of specific host protein substrates. We identified Arabidopsis methylthioadenosine nucleosidase proteins MTN1 and MTN2 as putative targets of HopAF1 deamidation. MTNs are enzymes in the Yang cycle, which is essential for the high levels of ethylene biosynthesis in Arabidopsis We hypothesized that HopAF1 inhibits the host defense response by manipulating MTN activity and consequently ethylene levels. We determined that bacterially delivered HopAF1 inhibits ethylene biosynthesis induced by pathogen-associated molecular patterns and that Arabidopsis mtn1 mtn2 mutant plants phenocopy the effect of HopAF1. Furthermore, we identified two conserved asparagines in MTN1 and MTN2 from Arabidopsis that confer loss of function phenotypes when deamidated via site specific mutation. These residues are potential targets of HopAF1 deamidation. HopAF1-mediated manipulation of Yang cycle MTN proteins is likely an evolutionarily conserved mechanism whereby HopAF1 orthologs from multiple plant pathogens contribute to disease in a large variety of plant hosts. PMID- 27274078 TI - Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization. AB - Anthraquinones are a large family of secondary metabolites (SMs) that are extensively studied for their diverse biological activities. These activities are determined by functional group decorations and the formation of dimers from anthraquinone monomers. Despite their numerous medicinal qualities, very few anthraquinone biosynthetic pathways have been elucidated so far, including the enzymatic dimerization steps. In this study, we report the elucidation of the biosynthesis of cladofulvin, an asymmetrical homodimer of nataloe-emodin produced by the fungus Cladosporium fulvum A gene cluster of 10 genes controls cladofulvin biosynthesis, which begins with the production of atrochrysone carboxylic acid by the polyketide synthase ClaG and the beta-lactamase ClaF. This compound is decarboxylated by ClaH to yield emodin, which is then converted to chrysophanol hydroquinone by the reductase ClaC and the dehydratase ClaB. We show that the predicted cytochrome P450 ClaM catalyzes the dimerization of nataloe-emodin to cladofulvin. Remarkably, such dimerization dramatically increases nataloe-emodin cytotoxicity against mammalian cell lines. These findings shed light on the enzymatic mechanisms involved in anthraquinone dimerization. Future characterization of the ClaM enzyme should facilitate engineering the biosynthesis of novel, potent, dimeric anthraquinones and structurally related compound families. PMID- 27274079 TI - The Pseudomonas aeruginosa efflux pump MexGHI-OpmD transports a natural phenazine that controls gene expression and biofilm development. AB - Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHI-OpmD in the opportunistic pathogen Pseudomonas aeruginosa Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHI OpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We also show that 5-Me-PCA is sufficient to fully induce MexGHI-OpmD expression and that it is required for wild-type colony biofilm morphogenesis. These physiological effects are consistent with the high redox potential of 5-Me-PCA, which distinguishes it from other well-studied P. aeruginosa phenazines. Our observations highlight the importance of this compound, which was previously overlooked due to the challenges associated with its detection, in the context of P. aeruginosa gene expression and multicellular behavior. This study constitutes a unique demonstration of efflux-based self-resistance, controlled by a simple circuit, in a Gram-negative pathogen. PMID- 27274081 TI - Temperature-field phase diagram of extreme magnetoresistance. AB - The recent discovery of extreme magnetoresistance (XMR) in LaSb introduced lanthanum monopnictides as a new platform to study this effect in the absence of broken inversion symmetry or protected linear band crossing. In this work, we report XMR in LaBi. Through a comparative study of magnetotransport effects in LaBi and LaSb, we construct a temperature-field phase diagram with triangular shape that illustrates how a magnetic field tunes the electronic behavior in these materials. We show that the triangular phase diagram can be generalized to other topological semimetals with different crystal structures and different chemical compositions. By comparing our experimental results to band structure calculations, we suggest that XMR in LaBi and LaSb originates from a combination of compensated electron-hole pockets and a particular orbital texture on the electron pocket. Such orbital texture is likely to be a generic feature of various topological semimetals, giving rise to their small residual resistivity at zero field and subject to strong scattering induced by a magnetic field. PMID- 27274080 TI - Plasma membrane/cell wall perturbation activates a novel cell cycle checkpoint during G1 in Saccharomyces cerevisiae. AB - Cellular wound healing or the repair of plasma membrane/cell wall damage (plasma membrane damage) occurs frequently in nature. Although various cellular perturbations, such as DNA damage, spindle misalignment, and impaired daughter cell formation, are monitored by cell cycle checkpoint mechanisms in budding yeast, whether plasma membrane damage is monitored by any of these checkpoints remains to be addressed. Here, we define the mechanism by which cells sense membrane damage and inhibit DNA replication. We found that the inhibition of DNA replication upon plasma membrane damage requires GSK3/Mck1-dependent degradation of Cdc6, a component of the prereplicative complex. Furthermore, the CDK inhibitor Sic1 is stabilized in response to plasma membrane damage, leading to cell integrity maintenance in parallel with the Mck1-Cdc6 pathway. Cells defective in both Cdc6 degradation and Sic1 stabilization failed to grow in the presence of plasma membrane damage. Taking these data together, we propose that plasma membrane damage triggers G1 arrest via Cdc6 degradation and Sic1 stabilization to promote the cellular wound healing process. PMID- 27274082 TI - Mobile phones and seizures: drug-resistant epilepsy is less common in mobile phone-using patients. AB - BACKGROUND: Epilepsy is a condition where patients have seizures due to abnormal nerve impulses in the brain. The effect of mobile phone radiation on patients with seizures is not known. OBJECTIVE: To compare the seizure profile of patients not using mobile phones with that of their peers using mobile phones. METHODS: In a retrospective cohort study performed at the neurology outpatient department of Guntur Medical College Hospital, Guntur, India from September 2014 to September 2015, we included 178 consecutive epileptic patients aged 16-65 years, who had had seizure disorder for 1 year or more. On the basis of their possession and usage of mobile phones, patients were divided into three groups: no mobile group (NMG), home mobile group (HMG) and personal mobile group (PMG). We obtained data on seizure frequency and recorded details of mobile phone usage and their antiepileptic drug (AED) treatment. RESULTS: 107 NMG, 3 HMG and 68 PMG patients were finalised for the analysis. There was no significant difference in the number of seizures in the past year between the three groups. The PMG (3.7%) contained a clinically significant lower proportion of patients with drug resistant epilepsy than the NMG (28.2%). Patients with drug-responsive epilepsy were 7.4 (95% CI 1.4 to 39.9) (p=0.01) times more likely to be found in the PMG than in the NMG after adjustment for differences in sex and occupation. CONCLUSIONS: Although the experimental data remain inconclusive, our clinical study suggests that patients who use mobile phones are less likely to have drug resistant epilepsy. PMID- 27274083 TI - Phlegmasia cerulea dolens. PMID- 27274084 TI - Broiler chicks with slow-feathering (K) or rapid-feathering (k+) genes: Effects of environmental stressors on physiological adaptive indicators up to 56 h posthatch. AB - Two experiments were conducted to examine the effects on the physiological responses of slow-feathering (K) and rapid-feathering (k(+)) genes in neonate broiler chicks subjected to posthatch fasting (PHF). In the first experiment, 300 Ross 308 chicks were denied access to feed and water for 0, 7, 14, 21, 28, 35, 42, 49, and 56 h posthatch. In the second experiment, 625 Ross 308 chicks were subjected to PHF for 0, 12, 24, 36, and 48 h. In experiment 1, the weight loss rate increased over 56 h PHF and did not differ between fast- and slow-feathering chicks up to 28 h posthatch but was greater (P < 0.05) in fast-feathering birds from 28 to 56 h posthatch. The fast-feathering genotypes demonstrated greater serum K levels following 7, 21, and 56 h (P < 0.05) and serum uric acid (UA) levels after 7, 21, 28, 49, and 56 h PHF (P < 0.01). In experiment 2, weight loss increased linearly with no difference between fast- and slow-feathering chicks through 36 h PHF but increased in fast-feathering birds when PHF continued for 48 h. Neonatal fasting periods of 12 to 48 h decreased breast and thigh percentage (P < 0.01), with no difference between feathering genotypes. The fast-feathering genotypes showed greater serum HDL levels at 24 h (P < 0.05) and greater serum UA concentration following 12, 36, and 48 h PHF (P < 0.05). The mean frequency of jumping (P < 0.01) and active wakefulness (P > 0.01) was increased as PHF continued from 12 to 48 h across genotypes. At 48 h, the fast-feathering chicks showed greater frequency of escape attempts from the test field (P < 0.01). It was concluded that slow-feathering chicks are more capable of withstanding PHF periods lasting more than 28 h. This is important to consider when day-old chicks are transported for extended periods without access to feed. PMID- 27274085 TI - Effect of sex on histological and histochemical structures of different parts of the kidney in Japanese quail. AB - The aim of the present study was to investigate the effect of gender on the histological and histochemical structures of different anatomical regions of the kidney in Japanese quail (Coturnix japonica). Tissue samples from cranial, middle and caudal divisions of each kidney were obtained from 20 male and 20 female adult, healthy Japanese quail. The sections stained with hematoxylin & eosin ( H & E: ), Masson's trichrome, Verhoeff's, Alcian blue (pH 2.5), Periodic acid Schiff, and Gomori's method for reticulum. Unusual findings of the kidney in Japanese quail were the presence of three types of nephrons, all the connective tissue fibers in capsule and interlobular septa and AB-reactions of the proximal convoluted cells. No significant sex-based differences were found. The various histological structures of the kidney showed no significant differences among different divisions of the left and right kidneys. It is concluded that the general histological and histochemical properties of the kidney in Japanese quail were similar to those of chickens and some other species, but that there were also some differences. One of the major differences was brush border of interdigitating microvilli on luminal surface of collecting ducts in Japanese quail. PMID- 27274086 TI - E2F and GATA switches turn off WD repeat domain 77 expression in differentiating cells. AB - WDR77 (WD repeat domain 77) is expressed during earlier lung development when cells are rapidly proliferating, but is absent from adult lung. It is re activated during lung tumorigenesis and is essential for lung cancer cell proliferation. Signalling pathways/molecules that control WDR77 gene expression are unknown. Promoter mapping, gel shift assay and ChIP revealed that the WDR77 promoter contains bona fide response elements for E2F and GATA transcriptional factors as demonstrated in prostate cancer, lung cancer and erythroid cells, as well as in mouse lung tissues. The WDR77 promoter is transactivated by E2F1, E2F3, GATA1 and GATA6, but suppressed by E2F6, GATA1 and GATA3 in prostate cancer PC3 cells. WDR77 expression is associated with E2F1, E2F3, GATA2 and GATA6 occupancy on the WDR77 gene, whereas, in contrast, E2F6, GATA1 and GATA3 occupancy is associated with the loss of WDR77 expression during erythroid maturation and lung development. More importantly, the loss of WDR77 expression that results from E2F and GATA switches is required for cellular differentiation of erythroid and lung epithelial cells. In contrast, lung cancer cells avoid post mitotic differentiation by sustaining WDR77 expression. Altogether, the present study provides a novel molecular mechanism by which WDR77 is regulated during erythroid and lung development and lung tumorigenesis. PMID- 27274088 TI - Proximity-dependent biotin labelling in yeast using the engineered ascorbate peroxidase APEX2. AB - The engineered ascorbate peroxidase (APEX2) has been effectively employed in mammalian cells to identify protein-protein interactions. APEX2 fused to a protein of interest covalently tags nearby proteins with biotin-phenol (BP) when H2O2 is added to the cell culture medium. Subsequent affinity purification of biotinylated proteins allows for identification by MS. BP labelling occurs in 1 min, providing temporal control of labelling. The APEX2 tool enables proteomic mapping of subcellular compartments as well as identification of dynamic protein complexes, and has emerged as a new methodology for proteomic analysis. Despite these advantages, a related APEX2 approach has not been developed for yeast. Here we report methods to enable APEX2-mediated biotin labelling in yeast. Our work demonstrated that high osmolarity and disruption of cell wall integrity permits live-cell biotin labelling in Schizosaccharomyces pombe and Saccharomyces cerevisiae respectively. Under these conditions, APEX2 permitted targeted and proximity-dependent labelling of proteins. The methods described herein set the stage for large-scale proteomic studies in yeast. With modifications, the method is also expected to be effective in other organisms with cell walls, such as bacteria and plants. PMID- 27274087 TI - Zinc transporter ZIP10 forms a heteromer with ZIP6 which regulates embryonic development and cell migration. AB - There is growing evidence that zinc and its transporters are involved in cell migration during development and in cancer. In the present study, we show that zinc transporter ZIP10 (SLC39A10) stimulates cell motility and proliferation, both in mammalian cells and in the zebrafish embryo. This is associated with inactivation of GSK (glycogen synthase kinase)-3alpha and -3beta and down regulation of E-cadherin (CDH1). Morpholino-mediated knockdown of zip10 causes delayed epiboly and deformities of the head, eye, heart and tail. Furthermore, zip10 deficiency results in overexpression of cdh1, zip6 and stat3, the latter gene product driving transcription of both zip6 and zip10 The non-redundant requirement of Zip6 and Zip10 for epithelial to mesenchymal transition (EMT) is consistent with our finding that they exist as a heteromer. We postulate that a subset of ZIPs carrying prion protein (PrP)-like ectodomains, including ZIP6 and ZIP10, are integral to cellular pathways and plasticity programmes, such as EMT. PMID- 27274089 TI - Antireduction: an ancient strategy fit for future. AB - While antioxidants are on everyone's lips, antireductants are their much less known counterparts. Following an antioxidant's definition, an antireductant prevents the chemical reduction of another compound by undergoing reduction itself. Antireductants have been traced back as far as the origin of life, which they facilitated by removal of atmospheric dihydrogen, H2 Moreover, as electron acceptors, antireductants equipped the first metabolic pathways, enabling lithoautotrophic microbial growth. When the Earth's atmosphere became more oxidizing, certain antireductants revealed their Janus-face by acting as antioxidants. Both capacities, united in one compound, were detected in primary as well as plant secondary metabolites. Substantiated by product identification, such antireductants comprise antiradicals (e.g. carotenoids) up to diminishers of ruminal methane emission (e.g. fumarate, catechin or resveratrol). Beyond these Janus-faced, multifunctional compounds, the spectrum of antireductants extends to pure electron-attractors (e.g. atmospheric triplet oxygen, O2, for plant root and gut protection). Current and prospective fields of antireductant application range from health promotion over industrial production to environmental sustainability. PMID- 27274090 TI - Extracting human antibody sequences from public databases for antibody humanization: high frequency of species assignment errors. AB - In antibody humanization, complementarity determining regions from a 'donor' antibody are often grafted onto a human framework selected by high sequence identity with the donor. In our own humanization experiments, we have found that species information is often incorrect. Here we take three mouse antibodies and perform BLAST searches against sequences annotated as being human. We find that the first genuine human hits for the six chains appear at Positions 30, 4, 11, 24, 18 and 29 in the hit lists. This illustrates both the need for caution in performing humanization and for improvements in annotation. PMID- 27274092 TI - High-Flow Nasal Cannula Versus Bag-Valve-Mask for Preoxygenation Before Intubation in Subjects With Hypoxemic Respiratory Failure. AB - BACKGROUND: Critically ill patients with respiratory failure undergoing intubation have an increased risk of hypoxemia-related complications. Delivering oxygen via a high-flow nasal cannula (HFNC) has theoretical advantages and is increasingly used. This study was conducted to compare HFNC with bag-valve-mask (BVM) for preoxygenation and to assess oxygenation during intubation in subjects with hypoxemic respiratory failure. METHODS: This study was a randomized controlled trial including 40 critically ill subjects with hypoxemic respiratory failure who received either HFNC or BVM for preoxygenation before intubation in the ICU. The primary outcome was the mean lowest SpO2 during intubation. RESULTS: The mean lowest SpO2 during intubation was 89 +/- 18% in the HFNC group and 86 +/ 11% in the BVM group (P = .56). In subjects receiving HFNC, a significant increase in SpO2 after preoxygenation was only seen in those previously receiving low-flow oxygen (P = .007), whereas there was no significant difference in SpO2 in subjects previously receiving noninvasive ventilation or HFNC (P = .73). During the 1 min of apnea after the induction of anesthesia, SpO2 dropped significantly in the BVM group (P = .001), whereas there was no significant decrease in the HFNC group (P = .17). There were no significant differences between the 2 groups at any of the predefined time points before or after intubation concerning SpO2 , PaO2 /FIO2 , and PaCO2 . CONCLUSIONS: Preoxygenation using HFNC before intubation was feasible and safe compared with BVM in critically ill subjects with acute, mild to moderate hypoxemic respiratory failure. There was no significant difference in the mean lowest SpO2 during intubation between the HFNC and the BVM group. There was also no significant difference in SpO2 between the 2 groups at any of the predefined time points. However, on continuous monitoring, there was a significant decrease in SpO2 during the apnea phase before intubation in the BVM group, which was not seen in the HFNC group. (ClinicalTrials.gov registration NCT01994928.). PMID- 27274091 TI - Consensus protein design. AB - A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering. PMID- 27274094 TI - Respiratory Therapists' Experiences and Attitudes Regarding Terminal Extubations and End-of-Life Care. AB - BACKGROUND: Respiratory therapists (RTs) routinely care for patients with life limiting illnesses and in some hospitals are responsible for terminal extubations. Data on how such experiences affect RTs are scarce. The objective of this work was to survey RTs at 2 academic medical centers about their experiences caring for patients with terminal extubations. METHODS: An online survey was distributed to the hospitals' RTs. Survey data included demographics and experiences with end-of-life care and terminal extubations. The survey was derived from previously published questionnaires plus input from hospital RT leaders. RESULTS: Sixty-five of 173 RTs (37.6%) responded. Of these, 42.4% were >=50 y old, and 62.7% were female. 20.3% had <=5 y experience; 52.5% had >=16 y. 93.8% self-reported being involved in at least one terminal extubation; of those, 36.1% reported performing >=20. Nearly half (47.5%) wanted to be involved in family meetings discussing terminal extubations, but just 6.6% were frequently involved. Only 32.3% felt that they received adequate education regarding terminal illness in RT school; 32.3% reported gathering this knowledge while working. 60.0% wanted more formal education around terminal patient care. 27.9% reported sometimes being uncomfortable with performing a terminal extubation; most of these rarely felt that they had the option not to perform the extubation. CONCLUSIONS: RTs are rarely involved in end-of-life discussions despite a desire to be, and they experience situations that generate discomfort. There is demand for more formal RT training around care for terminal patients. Clinical protocols that involve RTs in meetings before ventilator withdrawal should be considered. PMID- 27274093 TI - Induced Sputum Analysis in Subjects With Systemic Sclerosis. AB - BACKGROUND: Induced sputum is a noninvasive tool, aimed at collecting cellular and soluble materials from lung airways. Induced sputum sampling analysis has been validated in chronic obstructive lung diseases as well as in various diffuse interstitial lung disorders. Our objective was to evaluate the utility of induced sputum speciments of cellular and soluble materials noninvasively sampled from the lung airways of subjects with systemic sclerosis compared with healthy controls and determine possible correlation with disease manifestations. METHODS: The study population included 20 consecutive subjects with systemic sclerosis and 16 healthy volunteers (controls). All of the participants underwent pulmonary function testing (PFT), single-breath diffusion capacity of carbon monoxide, and induced sputum cytology analysis. RESULTS: The systemic sclerosis subjects' induced sputum samples contained a higher neutrophil count (P = .09) and lower lymphocyte count (P = .045) compared with the controls. Within the systemic sclerosis population, several clinical, PFT, and induced sputum findings were positively correlated: the modified Rodnan skin score score and CD3 (P = .044), modified Rodnan skin score and CD4 (P = .04), modified Rodnan skin score and percentage neutrophils (P = .059), and total lung capacity (TLC) and percentage lymphocytes (P = .02). Induced sputum neutrophil counts were inversely associated with TLC (P = .02) and FVC (P = .02). Induced sputum samples from the subgroup of systemic sclerosis subjects with PFT restrictive pattern contained a significantly lower percentage of lymphocytes (P = .004) and lower CD4/CD8 ratio (P = .03) compared with controls. In this subgroup, TLC also was negatively correlated with the neutrophil count (P = .043), and positive correlations were found between TLC and CD3 (P = .053), disease duration and CD4/CD8 ratio (P = .033), TLC and FVC and percentage macrophages (P = .033 and P = .052, respectively), diffusion per unit of alveolar volume, and percentage macrophages (P = .032), and C-reactive protein and percentage lymphocytes, percentage macrophages, and neutrophil count (P = .02, P = .008, and P = .006, respectively). CONCLUSIONS: Induced sputum analysis of subjects with systemic sclerosis, including those with restrictive lung disease, shows changes in cellular pattern and correlation with several highly relevant clinical and PFT parameters. PMID- 27274095 TI - High frequency of immunodeficiency-like states in systemic lupus erythematosus: a cross-sectional study in 300 consecutive patients. AB - OBJECTIVE: To determine the frequency of immunodeficiency-like states in SLE and related clinical features. METHODS: Three hundred and fifteen SLE patients and 301 controls were evaluated for C4A and C4B gene copy number, immunoglobulin isotypes, IgG subclasses, total haemolytic complement (CH50), C2, C3 and neutrophil oxidative burst. C2 and C3 genes were sequenced in cases of low C2 or C3 levels. Those presenting abnormal CH50 with normal C2 and C3 underwent C1q-C9 determination. Patients with active SLE and abnormal results were re-tested after the flare or were excluded if no remission was attained. Fifteen patients were excluded on this basis. Persistent abnormal results characterized an immunodeficiency-like state. RESULTS: A significantly higher percentage of SLE patients presented an immunodeficiency-like state compared with controls (28.7% vs 3.3%; P < 0.001), especially low immunoglobulin serum levels. Rigorous testing confirmed only two cases of C2 deficiency carriers among the SLE patients. There were significantly more SLE patients with less than two C4A copies compared with controls. SLE patients had higher frequency of low IgG2, IgG3, IgG4 and IgM levels compared with controls. Patients with low IgG3 or IgG4 presented higher frequency of lupus nephropathy. Patients with low IgM had longer disease duration, older age at SLE onset and lower frequency of oral ulcers. CONCLUSION: An immunodeficiency-like state is present in a sizable fraction of SLE patients. Further studies are warranted to determine the impact of these immunodeficiency states and whether they are a primary condition or are secondary to confounding factors, including SLE itself. PMID- 27274096 TI - Incidence of ANCA-associated vasculitis in a UK mixed ethnicity population. AB - OBJECTIVES: We aimed to estimate the incidence of ANCA-associated vasculitis in the UK and how this varied by ethnic group. METHODS: We identified incident cases of ANCA-associated vasculitis between March 2007 and June 2013 in the Nottingham Derby urban area from medical records using multiple sources. We derived the denominator population from the 2011 census, and we calculated incidence rate ratios using Poisson regression. RESULTS: Overall, we identified 107 cases of ANCA-associated vasculitis, giving an incidence of 23.1 per million person-years (95% CI: 18.9, 27.9). The incidence among the white population was 25.8 per million person-years (95% CI: 21.0, 31.3) and among the black and minority ethnic (BME) population 8.4 per million person-years (95% CI: 3.1, 18.3). After adjustment for age and sex, the difference between ethnic groups was not statistically significant (incidence rate ratio 0.7, 95% CI: 0.3, 1.5, P = 0.3). CONCLUSION: Overall, the incidence of ANCA-associated vasculitis was similar to other epidemiological studies. Crude incidence rates were lower in the BME than in the white population, but this was partly explained by the older age profile among the white compared with BME population. PMID- 27274097 TI - High-extinction virtually imaged phased array-based Brillouin spectroscopy of turbid biological media. AB - Brillouin microscopy has recently emerged as a powerful technique to characterize the mechanical properties of biological tissue, cell, and biomaterials. However, the potential of Brillouin microscopy is currently limited to transparent samples, because Brillouin spectrometers do not have sufficient spectral extinction to reject the predominant non-Brillouin scattered light of turbid media. To overcome this issue, we combined a multi-pass Fabry-Perot interferometer with a two-stage virtually imaged phased array spectrometer. The Fabry-Perot etalon acts as an ultra-narrow band-pass filter for Brillouin light with high spectral extinction and low loss. We report background-free Brillouin spectra from Intralipid solutions and up to 100 MUm deep within chicken muscle tissue. PMID- 27274098 TI - A major Calanus finmarchicus overwintering population inside a deep fjord in northern Norway: implications for cod larvae recruitment success. AB - High Calanus finmarchicus abundances were recorded in wintertime in Vestfjorden, close to the main cod breeding grounds off Lofoten and Vesteralen, northern Norway. The mean abundance for locations with water depth >500 m was ~37000 ind. m-2 (range: 26700-49000 ind. m-2). To our knowledge, this is the first report of massive overwintering of C. finmarchicus on the Norwegian shelf. Because of the observed size and location of this population, we argue that local overwintering on the northern Norwegian shelf can contribute significantly to sustain a C. finmarchicus population on the shelf during the period of first feeding for cod larvae. This is supported by a particle tracking model. PMID- 27274099 TI - Phylogeography and connectivity of the Pseudocalanus (Copepoda: Calanoida) species complex in the eastern North Pacific and the Pacific Arctic Region. AB - The genus Pseudocalanus (Copepoda, Calanoida) is among the most numerically dominant copepods in eastern North Pacific and Pacific-Arctic waters. We compared population connectivity and phylogeography based on DNA sequence variation for a portion of the mitochondrial cytochrome oxidase I gene for four Pseudocalanus species with differing biogeographical ranges within these ocean regions. Genetic analyses were linked to characterization of biological and physical environmental variables for each sampled region. Haplotype diversity was higher for the temperate species (Pseudocalanus mimus and Pseudocalanus newmani) than for the Arctic species (Pseudocalanus acuspes and Pseudocalanus minutus). Genetic differentiation among populations at regional scales was observed for all species, except P. minutus. The program Migrate-N tested the likelihood of alternative models of directional gene flow between sampled populations in relation to oceanographic features. Model results estimated predominantly northward gene flow from the Gulf of Alaska to the Beaufort Sea for P. newmani. Model scenarios that allowed bidirectional gene flow between sampled populations gave the best Bayesian predictions for P. acuspes, P. mimus and P. minutus. Under current warming trends, biogeographical boundaries and barriers for Pseudocalanus species may shift, allowing habitat range expansion or contraction and resulting in altered population connectivity between Arctic and sub-Arctic populations. PMID- 27274100 TI - Metabolically active, non-nitrogen fixing, Trichodesmium in UK coastal waters during winter. AB - Trichodesmium, a colonial cyanobacterium typically associated with tropical waters, was observed between January and April 2014 in the western English Channel. Sequencing of the heterocyst differentiation (hetR) and 16S rRNA genes placed this community within the Clade IV Trichodesmium, an understudied clade previously found only in low numbers in warmer waters. Nitrogen fixation was not detected although measurable rates of nitrate uptake and carbon fixation were observed. Trichodesmium RuBisCO transcript abundance relative to gene abundance suggests the potential for viable and potentially active Trichodesmium carbon fixation. Observations of Trichodesmium when coupled with a numerical advection model indicate that Trichodesmium communities can remain viable for >3.5 months at temperatures lower than previously expected. The results suggest that Clade IV Trichodesmium occupies a different niche to other Trichodesmium species, and is a cold- or low-light-adapted variant. PMID- 27274101 TI - siRNA-induced silencing of hypoxia-inducible factor 3alpha (HIF3alpha) increases endurance capacity in rats. AB - Molecular mechanisms of adaptation to exercise despite a large number of studies remain unclear. One of the crucial factors in this process is hypoxia inducible factor (HIF) that regulates transcription of many target genes encoding proteins that are implicated in molecular adaptation to hypoxia. Experiments were conducted on 24 adult male Fisher rats. Real-time PCR analysis was performed for quantitative evaluation of Hif3alpha, Igf1, Glut-4 and Pdk-1 in m. gastrocnemius, m. soleus, in lung and heart tissues. Mitochondrial respiratory function and electron microscopy were performed. Knockdown of Hif3alpha using siRNA increases time of swimming to exhaustion by 1.5 times. Level of mitochondrial NAD- and FAD dependent oxidative pathways is decreased, however efficiency of phosphorylation is increased after Hif3alpha siRNA treatment. Expression of HIF target genes in muscles was not changed significantly, except for increasing of Pdk-1 expression in m. soleus by 2.1 times. More prominent changes were estimated in lung and heart: Igf1 gene expression was increased by 32.5 and 37.5 times correspondingly. Glut4 gene expression in lungs was increased from undetected level till 0.3 rel. units and by 84.2 times in heart. Level of Pdk1 gene expression was increased by 249.2 in lungs and by 35.1 times in hearts, correspondingly. Some destructive changes in muscle tissue were detected in animals with siRNA-inducing silencing of Hif3alpha. PMID- 27274102 TI - Expression of SCGB1C1 gene as a potential marker of susceptibility to upper respiratory tract infections in elite athletes - a pilot study. AB - High levels of exercise in athletes result in temporary immunosuppression, which could increase the susceptibility to upper respiratory tract infections. Understanding of immunological mechanisms responsible for this phenomenon could enable optimization of training schemes for elite athletes and avoidance of infection-related episodes of absence during sports championships. The aim of this study was to detect genes that may be responsible for modulation of individual susceptibility to infections. The blood and saliva samples were collected from 10 healthy, medically examined kayakers (4 females and 6 males) aged 24.7 +/- 2.3 years. All samples were taken in the morning, after overnight fasting, in a seated position. The ELISA method was used to determine the levels of secretory immunoglobulin A (sIgA) and interleukin 5 (IL-5). Whole genome expression in blood was assessed using microarrays. The study did not reveal any significant correlation between genome expression and sIgA concentration. However, low expression of a gene involved in protection against the common cold secretoglobin 1C1 (SCGB1C1) - was detected in athletes with high IL-5 concentrations (corrected p = 0.00065; fold change = 3.17). Our results suggest that blood expression of the SCGB1C1 gene might be a marker of susceptibility to upper respiratory tract infections in athletes. PMID- 27274103 TI - The effects of two equal-volume training protocols upon strength, body composition and salivary hormones in male rugby union players. AB - This study examined the effects of two equal-volume resistance-training protocols upon strength, body composition and salivary hormones in male rugby union players. Using a crossover design, 24 male rugby players completed a 4-week full body (FB) and split-body (SB) training protocol of equal volume during the competitive season. One repetition maximum (1RM) strength, body composition via skinfold measurements and salivary testosterone (T) and cortisol (C) concentrations were assessed pre and post training. The FB and SB protocols improved upper (7.3% and 7.4%) and lower body 1RM strength (7.4% and 5.4%), whilst reducing body fat (-0.9% and -0.4%) and fat mass (-5.7% and -2.1%), respectively (all p <= 0.021). The SB protocol elevated T (21%) and C (50%) concentrations with a higher T/C ratio (28%) after FB training (all p <= 0.039). The strength changes were similar, but the body composition and hormonal results differed by protocol. Slope testing on the individual responses identified positive associations (p <= 0.05) between T and C concentrations and absolute 1RM strength in stronger (squat 1RM = 150.5 kg), but not weaker (squat 1RM = 117.4 kg), men. A short window of training involving FB or SB protocols can improve strength and body composition in rugby players. The similar strength gains highlight training volume as a key adaptive stimulus, although the programme structure (i.e. FB or SB) did influence the body composition and hormonal outcomes. It also appears that 1RM strength is associated with individual hormonal changes and baseline strength. PMID- 27274104 TI - A genetic-based algorithm for personalized resistance training. AB - Association studies have identified dozens of genetic variants linked to training responses and sport-related traits. However, no intervention studies utilizing the idea of personalised training based on athlete's genetic profile have been conducted. Here we propose an algorithm that allows achieving greater results in response to high- or low-intensity resistance training programs by predicting athlete's potential for the development of power and endurance qualities with the panel of 15 performance-associated gene polymorphisms. To develop and validate such an algorithm we performed two studies in independent cohorts of male athletes (study 1: athletes from different sports (n = 28); study 2: soccer players (n = 39)). In both studies athletes completed an eight-week high- or low intensity resistance training program, which either matched or mismatched their individual genotype. Two variables of explosive power and aerobic fitness, as measured by the countermovement jump (CMJ) and aerobic 3-min cycle test (Aero3) were assessed pre and post 8 weeks of resistance training. In study 1, the athletes from the matched groups (i.e. high-intensity trained with power genotype or low-intensity trained with endurance genotype) significantly increased results in CMJ (P = 0.0005) and Aero3 (P = 0.0004). Whereas, athletes from the mismatched group (i.e. high-intensity trained with endurance genotype or low-intensity trained with power genotype) demonstrated non-significant improvements in CMJ (P = 0.175) and less prominent results in Aero3 (P = 0.0134). In study 2, soccer players from the matched group also demonstrated significantly greater (P < 0.0001) performance changes in both tests compared to the mismatched group. Among non- or low responders of both studies, 82% of athletes (both for CMJ and Aero3) were from the mismatched group (P < 0.0001). Our results indicate that matching the individual's genotype with the appropriate training modality leads to more effective resistance training. The developed algorithm may be used to guide individualised resistance-training interventions. PMID- 27274105 TI - Effects of recreational soccer on physical fitness and health indices in sedentary healthy and unhealthy subjects. AB - Recreational soccer (RS) is becoming a popular alternative to the classical continuous exercise mode used for the improvement of cardiovascular and metabolic fitness in untrained people. The objective of this paper was to conduct a detailed systematic review of the literature, identifying the physiological responses to RS and the training effects of RS on aerobic fitness and health in untrained healthy individuals and clinical patients. PubMed, Google Scholar and ScienceDirect databases were searched using terms related to recreational soccer. Inclusion criteria were randomized controlled trials (RCT) that assessed acute physiological responses to RS or the training effects of RS on physical fitness and health in sedentary, untrained subjects of any age or health status. All studies were assessed for methodological quality using the PEDro scale. Thirty five articles met the inclusion criteria; seven examined the acute response to RS, and 28 assessed training effects. Clear evidence was found that RS had positive effects on many health-related indices and variables, including VO2max (gains of 7-16%), blood pressure (reductions of 6-13 mmHg), body composition (decreased fat mass and improved indices of bone health), and metabolic and cardiac function. These positive effects were observed in both healthy individuals and clinical patients, irrespective of age or sex. Although this review provides clear evidence of the positive effects of RS on health, most studies had limitations of methodology (an average PEDro score < 6). Furthermore, many of the training studies were from a small number of research groups. Future studies should be extended to other countries and institutions to ensure generality of the results. Regular RS training leads to significant cardiovascular and muscular adaptations and gains of health both in sedentary individuals and clinical patients at all ages, suggesting that RS is a potentially highly motivational method to enhance population health. PMID- 27274106 TI - High intensity interval and moderate continuous cycle training in a physical education programme improves health-related fitness in young females. AB - The aim of the study was to investigate the effects of eight weeks of regular physical education classes supplemented with high intensity interval cycle exercise (HIIE) or continuous cycle exercises of moderate intensity (CME). Forty eight collegiate females exercising in two regular physical education classes per week were randomly assigned to two programmes (HIIE; n = 24 or CME; n = 24) of additional (one session of 63 minutes per week) physical activity for 8 weeks. Participants performed HIIE comprising 2 series of 6x10 s sprinting with maximal pedalling cadence and active recovery pedalling with intensity 65%-75% HRmax or performed CME corresponding to 65%-75% HRmax. Before and after the 8-week programmes, anthropometric data and aero- and anaerobic capacity were measured. Two-way ANOVA revealed a significant time main effect for VO2max (p < 0.001), similar improvements being found in both groups (+12% in HIIE and +11% in CME), despite body mass not changing significantly (p = 0.59; +0.4% in HIIE and -0.1% in CME). A significant main time effect was found for relative fat mass (FM) and fat-free mass (FFM) (p < 0.001 and p < 0.001, respectively). A group x time interaction effect was found for relative FM and FFM (p = 0.018 and p = 0.018); a greater reduction in FM and greater increase in FFM were noted in the CME than the HIIE group. Improvements in anaerobic power were observed in both groups (p < 0.001), but it was greater in the HIIE group (interaction effect, p = 0.022). Weight loss is not mandatory for exercise-induced effects on improving aerobic and anaerobic capacity in collegiate females. Eight weeks of regular physical education classes supplemented with CME sessions are more effective in improving body composition than physical education classes supplemented with HIIE sessions. In contrast to earlier, smaller trials, similar improvements in aerobic capacity were observed following physical activity with additional HIIE or CME sessions. PMID- 27274107 TI - Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females. AB - This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p < 0.05) body mass (BM), BMI Z-score, and percentage of body fat (%BF). Only the HIIT group showed decreased waist circumference (WC) (p = 0.017). The effect of exercise on maximal oxygen uptake (VO2max) was significant (p = 0.019, ES = 0.48 and p = 0.010, ES = 0.57, HIIT and MIIT, respectively). The decrease of rate-pressure product (RPP) (p < 0.05, ES = 0.53 and ES = 0.46, HIIT and MIIT, respectively) followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p < 0.05) in both training groups. Significant decreases occurred in blood leptin (p = 0.021, ES = 0.67 and p = 0.011, ES = 0.73) and in RPE (p = 0.001, ES = 0.76 and p = 0.017, ES = 0.57) in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p < 0.001) and VO2max (p < 0.01) in the HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p < 0.01) in the HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity. PMID- 27274108 TI - Acute effects of concentric and eccentric exercise on glucose metabolism and interleukin-6 concentration in healthy males. AB - Acute muscle-damaging eccentric exercise (EE) negatively affects glucose metabolism. On the other hand, long-term eccentric endurance exercise seems to result in equal or superior positive effects on glucose metabolism compared to concentric endurance exercise. However, it is not known if acute non-muscle damaging EE will have the same positive effects on glucose metabolism as acute concentric exercise (CE). Interleukin-6 (IL-6) released from the exercising muscles may be involved in the acute adaptations of glucose metabolism after CE and non-muscle-damaging EE. The aim of this study was to assess acute effects of uphill walking (CE) and non-muscle-damaging downhill walking (EE) on glucose metabolism and IL-6 secretion. Seven sedentary non-smoking, healthy males participated in a crossover trial consisting of a 1 h uphill (CE) and a 1 h downhill (EE) walking block on a treadmill. Venous blood samples were drawn before (pre), directly after (acute) and 24 h after (post) exercise. An oral glucose tolerance test (OGTT) was performed before and 24 h after exercise. Glucose tolerance after 1 and 2 hours significantly improved 24 hours after CE ( 10.12+/-3.22%: P=0.039; -13.40+/-8.24%: P=0.028). After EE only the 1-hour value was improved (-5.03+/-5.48%: P=0.043). Acute IL-6 concentration rose significantly after CE but not after EE. We conclude that both a single bout of CE and a single bout of non-muscle-damaging EE elicit positive changes in glucose tolerance even in young, healthy subjects. Our experiment indicates that the overall metabolic cost is a major trigger for acute adaptations of glucose tolerance after exercise, but only the IL-6 production during EE was closely related to changes in glycaemic control. PMID- 27274109 TI - Reliability and criterion-related validity of a new repeated agility test. AB - The study aimed to assess the reliability and the criterion-related validity of a new repeated sprint T-test (RSTT) that includes intense multidirectional intermittent efforts. The RSTT consisted of 7 maximal repeated executions of the agility T-test with 25 s of passive recovery rest in between. Forty-five team sports players performed two RSTTs separated by 3 days to assess the reliability of best time (BT) and total time (TT) of the RSTT. The intra-class correlation coefficient analysis revealed a high relative reliability between test and retest for BT and TT (>0.90). The standard error of measurement (<0.50) showed that the RSTT has a good absolute reliability. The minimal detectable change values for BT and TT related to the RSTT were 0.09 s and 0.58 s, respectively. To check the criterion-related validity of the RSTT, players performed a repeated linear sprint (RLS) and a repeated sprint with changes of direction (RSCD). Significant correlations between the BT and TT of the RLS, RSCD and RSTT were observed (p<0.001). The RSTT is, therefore, a reliable and valid measure of the intermittent repeated sprint agility performance. As this ability is required in all team sports, it is suggested that team sports coaches, fitness coaches and sports scientists consider this test in their training follow-up. PMID- 27274110 TI - Effect of between-set recovery durations on repeated sprint ability in young soccer players. AB - The purposes of this study were to examine the effect of between-set recovery duration on physiological responses (heart rate and blood lactate), rating of perceived exertion (RPE) and performance indices of repeated sprint sets (RSS) and to investigate their relationship with aerobic power. Twenty-four young male soccer players (age: 17.4 +/- 0.32 years) performed three randomized RSS protocols consisting of 2 sets of 5x20 m with 15 s recovery between sprints and 1 min (RSS1), 2 min (RSS2) and 4 min (RSS4) between sets, and a multi-stage aerobic track test to estimate VO2max. Results showed that in contrast to RSS2 and RSS4, RSS1 leads to a large decline in performance expressed as the sum of sprint times (34.0+/-1.0 s, 34.0+/-1.1s and 34.6+/-1.1s, respectively) and a significant increase of both mean heart rate (124.0+/-9.7 bpm, 112.5+/-6.7 bpm and 137.3+/ 12.4, respectively) and RPE (3.2+/-1.5, 3.4+/-1.2 and 6.3+/-1.4, respectively) with no change in blood lactate and peak HR between the three rest conditions. No significant correlations were obtained between estimated VO2max and any of the indices of the three RSS protocols. In conclusion, 1 min of recovery between sets is sufficient to ensure a significant decrease in performance in the second set, while 2 min and 4 min of recovery were long enough to provide maintenance of high intensity work in the second set. These findings would be useful for coaches and sport scientists when attempting to assess repeated sprint abilities, allowing coaches to accurately define the intended training goals in young soccer players. PMID- 27274112 TI - Bilateral and unilateral vertical ground reaction forces and leg asymmetries in soccer players. AB - The purposes of this study were to assess unilateral and bilateral vertical jump performance characteristics, and to compare the vertical ground reaction force characteristics of the impulse and landing phase of a vertical jump between the dominant and non-dominant leg in soccer players. The sample consisted of 20 male soccer players (22.80 +/- 2.71 years, 1.88 +/- 0.06 m, 76.47 +/- 8.80 kg) who competed in the third division of the Spanish football league. Vertical jump performance was determined by testing the impulse and landing phase of a bilateral vertical jump, dominant leg vertical jump and non-dominant leg vertical jump. Significant differences (p < 0.05) between dominant and non-dominant legs were found in counter movement jump (CMJ) flight time (LA = -2.38%, d = 0.33), CMJ flight height (LA = -4.55%, d = 0.33) and CMJ speed take-off (LA = -2.91%, d = 0.42). No significant differences were found between the dominant and non dominant leg in the F1 and F2 magnitudes during the landing phase, the time from the first contact of the foot with the ground to the production of F1, the time from the second contact of the foot with the ground to the production of F2, and the time to stabilization of the landing phase. Although differences were found between the dominant and non-dominant leg in the impulse phase of the jump, no significant differences were found between dominant and non-dominant legs in the landing phase of vertical jump variables. PMID- 27274111 TI - Change of direction ability test differentiates higher level and lower level soccer referees. AB - This report examines the agility and level of acceleration capacity of Spanish soccer referees and investigates the possible differences between field referees of different categories. The speed test consisted of 3 maximum acceleration stretches of 15 metres. The change of direction ability (CODA) test used in this study was a modification of the Modified Agility Test (MAT). The study included a sample of 41 Spanish soccer field referees from the Navarre Committee of Soccer Referees divided into two groups: i) the higher level group (G1, n = 20): 2ndA, 2ndB and 3rd division referees from the Spanish National Soccer League (28.43 +/- 1.39 years); and ii) the lower level group (G2, n = 21): Navarre Provincial League soccer referees (29.54 +/- 1.87 years). Significant differences were found with respect to the CODA between G1 (5.72 +/- 0.13 s) and G2 (6.06 +/- 0.30 s), while no differences were encountered between groups in acceleration ability. No significant correlations were obtained in G1 between agility and the capacity to accelerate. Significant correlations were found between sprint and agility times in the G2 and in the total group. The results of this study showed that agility can be used as a discriminating factor for differentiating between national and regional field referees; however, no observable differences were found over the 5 and 15 m sprint tests. PMID- 27274113 TI - Within- and between-session reliability of medial gastrocnemius architectural properties. AB - This study aimed to determine the within- and between-session reliability of medial gastrocnemius (MG) architecture (e.g. muscle thickness (MT), fascicle length (FL) and pennation angle (PA)), as derived via ultrasonography followed by manual digitization. A single rater recorded three ultrasound images of the relaxed MG muscle belly for both legs of 16 resistance trained males, who were positioned in a pronated position with their knees fully extended and the ankles in a neutral (e.g. 90 degrees ) position. A subset of participants (n = 11) were retested under the same conditions ~48-72 hours after baseline testing. The same rater manually digitized each ultrasound image on three occasions to determine MG MT, FL and PA before pooling the data accordingly to allow for within-image (n = 96), between-image (n = 32) and between-session reliability (n = 22) to be determined. Intraclass correlation coefficients (ICCs) demonstrated excellent within-image (ICCs = 0.99-1.00, P < 0.001) and very good between-image (ICCs = 0.83-0.95, P < 0.001) and between-session (ICCs = 0.89-0.95, P < 0.001) reliability for MT, FL and PA. Between-session coefficient of variation was low (<= 3.6%) for each architectural parameter and smallest detectible difference values of 10.6%, 11.4% and 9.8% were attained for MT, FL and PA, respectively. Manually digitizing ultrasound images of the MG muscle at rest yields highly reliable measurements of its architectural properties. Furthermore, changes in MG MT, FL and PA of >= 10.6%, 11.4% and 9.8% respectively, as brought about by any form of intervention, should be considered meaningful. PMID- 27274114 TI - Performance profile of NCAA Division I men's basketball games and training sessions. AB - This study aimed to analyse live and stoppage time phases, their ratio, and action played on half and full court in college basketball games. Differences were assessed for the entire games and between halves. Moreover, differences of the live/stoppage time ratio were analysed between games and game-based conditioning drills. Ten games as well as fifteen defensive, fourteen offensive and six scrimmage-type drills of the same division I men's college team (13 players) were analysed using time-motion analysis technique. Live and stoppage time were classified in five classes of duration: 1-20, 21-40, 41-60, 61-80, >80 seconds. Half court actions started and finished in the same half court. Full court actions were classified as transfer (TR) phases when at least 3 teammates crossed the mid-court line. TR phases were then classified in 5 classes of frequency: 1TR, 2TR, 3TR, 4TR, and >4TR. The results revealed no statistically significant differences between games or between halves for the considered parameters. The only significant difference was observed for live/stoppage time ratio between halves (p<0.001). Furthermore, a significant difference of the live/stoppage ratio was found between games and game-based drills (p<0.01). Post hoc analysis demonstrated significant differences of scrimmage-type drills in comparison to games, and defensive and offensive drills (p<0.05), whereas no differences emerged for the other pairwise comparisons. The absence of differences between games in the analysed parameters might be important to characterize the model of performance in division I men's college games. Furthermore, these results encourage coaches to use game-based conditioning drills to replicate the LT/ST ratio documented during games. PMID- 27274115 TI - Privileges. PMID- 27274116 TI - Reed O. Dingman. PMID- 27274117 TI - Novel expansion techniques for skin grafts. AB - The quest for skin expansion is not restricted to cover a large area alone, but to produce acceptable uniform surfaces, robust engraftment to withstand mechanical shear and infection, with a minimal donor morbidity. Ease of the technique, shorter healing period and reproducible results are essential parameters to adopt novel techniques. Significant advances seen in four fronts of autologous grafting are: (1) Dermal-epidermal graft expansion techniques, (2) epidermal graft harvests technique, (3) melanocyte-rich basal cell therapy for vitiligo and (4) robust and faster autologous cell cultures. Meek's original concept that the sum of perimeter of smaller grafts is larger than the harvested graft, and smaller the graft size, the greater is the potential for regeneration is witnessed in newer modification. Further, as graft size becomes smaller or minced, these micrografts can survive on the wound bed exudate irrespective of their dermal orientation. Expansion produced by 4 mm * 4 mm sized Meek micrografts is 10-folds, similarly 0.8 mm * 0.8 mm size micrografts produce 100 fold expansion, which becomes 700-fold with pixel grafts of 0.3 mm * 0.3 mm size. Fractional skin harvest is another new technique with 700 MU size full thickness graft. These provide instant autologous non-cultured graft to cover extensive areas with similar quality of engraftment surface as split skin grafts. Newer tools for epidermal blister graft harvest quickly, with uniform size to produce 7 fold expansions with reproducible results. In addition, donor area heals faster with minimal scar. Melanocyte-rich cell suspension is utilised in vitiligo surgery tapping the potential of hair root melanocytes. Further advances in the cell culture to reduce the cultivation time and provide stronger epidermal sheets with dermal carrier are seen in trials. PMID- 27274118 TI - Functional outcomes of post-traumatic metacarpal hand reconstruction with free toe-to-hand transfer. AB - INTRODUCTION: We present the functional outcomes of microvascular toe transfer to reconstruct the post-traumatic metacarpal hand deformity. Twelve toe transfers were successfully carried out in 11 patients. MATERIALS AND METHODS: In each patient, the level of injury was classified according to the Wei classification system. Functional outcome was measured in seven patients using the Tamai score. Additional objective tests of function were carried out in three patients, including the Jebsen test, grip strength, pinch strength, web opening, static and moving two-point discrimination and Semmes-Weinstein monofilament testing. OBSERVATION AND RESULTS: The average Tamai score was 69 (range 60-83.5). Six patients achieved 'good' outcomes and one patient, with a double toe transfer, an 'excellent' outcome. The average follow-up time was 43 months (range 10-148 months). CONCLUSION: This study shows how even a single toe transfer can restore useful function to a hand that has otherwise lost all prehensile ability. PMID- 27274119 TI - Management of fourth degree obstetric perineal tear without colostomy using non - stimulated gracilis - our experience over eleven years. AB - BACKGROUND: Although gracilis muscle transposition for faecal incontinence has been well-described method, its literature for use in obstetric perineal tear without colostomy is sparse. In this study, we have tried to analyse its use in fourth-degree obstetric perineal tears. PATIENTS AND METHODS: A total of 30 patients with recto-vaginal fistula with faecal incontinence secondary to obstetric perineal tear were retrospectively studied between February 2003 and May 2014. The recto-vaginal fistula was explored, dissected and identification of sphincters was done using muscle stimulator. Fistula closure was done followed by sphincter repair, vaginal tightening procedure and single gracilis transposition. None of the patients had covering colostomy. Faecal incontinence was assessed pre and post-operatively by digital rectal examination (single examiner), Park's score and Corman's score in all cases and using barium hold and transperineal ultrasonography, manometric studies in a few cases. The outcome was measured at an average follow-up of 8.8 months (7-24 months). RESULTS: As per Park's score 26 patients had Grade I continence, two had Grade II and two patients had Grade III continence. Corman's score improved from fair to excellent in 26 patients. The patients in whom manometry was performed showed a remarkable rise in both resting and squeeze pressures. Two patients developed post-operative infections in upper 1/3 thigh incision site and three patients at gluteal region scar site. CONCLUSION: Satisfactory continence following gracilis muscle could be achieved. PMID- 27274120 TI - A case series of flow-through free anterolateral thigh flap to augment the vascularity of ischaemic limbs with soft tissue defect. AB - INTRODUCTION: In a world of fast moving vehicles, heavy machinery and industries crush injury to limbs with vascular compromise and soft tissue defect is common. The traditional treatment is a 2 step one dealing with vascular repair and soft tissue cover separately, in the same operation. We report a series of single step vascular repair and soft tissue cover with flow through anterolateral thigh flap (ALT) flap for limb salvage. MATERIALS AND METHODS: Ten patients with soft tissue defect and vascular injury were included in this study. A two team approach was used to minimise operative time, team one prepared the vessels and team 2 harvested the flap. OBSERVATIONS AND RESULTS: Of the ten patients operated (8 males), eight flaps were done for upper limb and two for lower limb salvage. Six anastomosis were done with ulnar vessels, two with radial and two with posterior tibial vessels. Nine extremities could be salvaged while one patient developed progressive thrombosis leading to amputation. CONCLUSION: The ALT flow-through flap is a versatile single step procedure that can be used to salvage an ischemic limb with soft tissue loss avoiding the need for interpositional vein graft. PMID- 27274121 TI - Presurgical nasoalveolar moulding in unilateral cleft lip and palate. AB - CONTEXT: Presurgical nasoalveolar moulding (PNAM) is a non-surgical method of reshaping the cleft lip, alveolus, palate and the nose to minimize the severity of the cleft deformity, before primary cheiloplastyand palatoplasty. In this context, PNAM proves to be an invaluable asset in the management of unilateral cleft lip and palate. AIMS: The study was conducted to evaluate the efficacy of PNAM in the management of unilateral cleft lip and palate with the following objectives: (1) To assess and compare the degree of reduction in the size of cleft palate and alveolus (pre-PNAM and post-PNAM). (2) To evaluate and compare the improvement in columellar length and correction of columellar deviation (pre PNAM and post-PNAM). (3) To assess the changes in the position of the alar base and the alar cartilages. SETTINGS AND DESIGN: Prospective study. SUBJECTS AND METHODS: A prospective study consisting of, which included 20 patients with complete unilateral cleft lip and palate was conducted. The age at the start of PNAM treatment of the infants ranged from 2 to 44 days of age reporting to our institute between December 2011 and August 2013. All the patients underwent PNAM therapy before primary cheiloplasty at 6 months of age; clinical parameters were assessed pre- and post-therapy using photographs and dental study models of the maxilla. STATISTICAL ANALYSIS USED: Student's t-test for paired comparisons. RESULTS: Results of the study showed a promising reduction in the cleft size before the surgery, significant improvement in nasal symmetry, including the columellar length on the cleft side. CONCLUSIONS: PNAM is a valuable adjunct to our surgical armamentarium in dealing with the challenges of primary closure of unilateral cleft lip and palate thereby enhancing the overall surgical outcome. The advantages of this method include the simplicity of the procedure and improving the quality of surgical repair, particularly in obtaining tension free muscle closure in unilateral clefts. PMID- 27274122 TI - Cadaveric study using radio-opaque contrast to determine arterial communication between the two bellies of gastrocnemius muscles. AB - INTRODUCTION: Gastrocnemius muscle is a workhorse flap to cover upper third tibial defects but has a limitation in covering middle one-third tibial defects. The inferiorly based hemi gastrocnemius muscle flap can be useful for reconstruction of the middle third of the leg. The arterial communication between the gastrocnemius muscle heads has been demonstrated, the consistent location, however, was not studied in large specimens. MATERIALS AND METHODS: This study was conducted on sixty specimens of gastrocnemius muscles harvested from thirty fresh cadavers to determine arterial communication between two heads of gastrocnemius muscle using radio-opaque contrast with future application of taking one head of muscle distally based for coverage of middle third defect of tibia. A total of 60 specimens were obtained from thirty fresh cadavers. In thirty specimens, medial sural artery ligated and divided and 20 ml iohexol (350) given through popliteal artery. In remaining thirty specimens lateral sural artery ligated and divided and 20 ml iohexol (350) given through popliteal artery. Digital X-rays of gastrocnemius muscle specimens were taken, and collaterals between two bellies in lower half were noted and the distance of collaterals from the muscles top edge was also noted. RESULTS: We found the communications between both bellies of the gastrocnemius muscle in all specimens in both legs. The mean distance of communications from the upper edge of the medial belly was 15.88 cm and from upper edge of the lateral belly was 14.72 cm in the right leg, respectively. The mean distance of communications from upper edge of the medial belly was 16.01 cm and from upper edge of the lateral belly was 13.78 cm in the left leg. The distal communications between gastrocnemius bellies were not constant in their location, but all the connections were present in distal 3.79 cm of raphe. CONCLUSION: This study supports the future application of inferior-based hemigastrocnemius muscles flap to cover defects of middle third leg. When distally based hemigastrocnemius flap is planned roughly 1/3(rd) of distal attachment or distal 3.79 cm of connection between raphe should be maintained to preserve the vascular communications between the two bellies. PMID- 27274123 TI - Preauricular transmasseteric anteroparotid approach for extracorporeal fixation of mandibular condyle fractures. AB - INTRODUCTION: Free grafting or extracorporeal fixation of traumatically displaced mandibular condyles is sometimes required in patients with severe anteromedial displacement of condylar head. Majority of the published studies report the use of a submandibular, retromandibular or preauricular incisions for the access which have demerits of limited visibility, access and potential to cause damage to facial nerve and other parotid gland related complications. PURPOSE: This retrospective clinical case record study was done to evaluate the preauricular transmasseteric anteroparotid (P-TMAP) approach for open reduction and extracorporeal fixation of displaced and dislocated high condylar fractures of the mandible. PATIENTS AND METHODS: This retrospective study involved search of clinical case records of seven patients with displaced and dislocated high condylar fractures treated by open reduction and extracorporeal fixation over a 3 year period. The parameters assessed were as follows: a) the ease of access for retrieval, reimplantation and fixation of the proximal segment; b) the postoperative approach related complications; c) the adequacy of anatomical reduction and stability of fixation; d) the occlusal changes; and the e) TMJ function and radiological changes. RESULTS: Accessibility and visibility were good. Accurate anatomical reduction and fixation were achieved in all the patients. The recorded complications were minimal and transient. Facial nerve (buccal branch) palsy was noted in one patient with spontaneous resolution within 3 months. No cases of sialocele or Frey's syndrome were seen. CONCLUSION: The P TMAP approach provides good access for open reduction and extracorporeal fixation of severely displaced condylar fractures. It facilitates retrieval, transplantation, repositioning, fixing the condyle and also reduces the chances of requirement of a vertical ramus osteotomy. It gives straight-line access to condylar head and ramus thereby permitting perpendicular placement of screws with minimal risk of damage to the facial nerve. PMID- 27274124 TI - Direct brow lifting: Specific indications for a simplified approach to eyebrow ptosis. AB - CONTEXT: Brow lifting is an essential element in the rejuvenation of the ageing face. Various surgical techniques have been described. Among these, the direct brow lifting is an easy and effective technique that is often neglected because the scar can remain visible. Thus, this approach is usually reserved for elderly patients and males, with thick bushy brows. AIMS: The authors present their result from a series of fifty consecutive patients treated over 2 years with direct brow lift. The aim is to demonstrate when the hairline is high or temporal alopecia is present and whether this technique is the best in bald patients, when some surgical steps are carefully adhered to. In these cases, the scar is less visible, hidden in the brow and is a good solution in women too. SUBJECTS AND METHODS: Between January 2011 and January 2013, fifty patients underwent direct brow lift surgery. All were men. In all the cases, brow lifting was undertaken together with an upper blepharoplasty. The amount of brow elevation produced was assessed by comparing the vertical distances between the superior eyebrow hairline and the inter-pupillary line, pre- and post-operatively. The result and the scar quality were assessed both by the patient and the surgeon. STATISTICAL ANALYSIS USED: The paired t-test. RESULTS: The authors obtained statistically significant results in brow elevation in 98% of the patients after a 12-month follow-up. The main complication associated with this procedure was visibility of the scar in two patients. CONCLUSIONS: The direct brow lift technique in bald men and with a high anterior hairline provides excellent and long-lasting results. PMID- 27274125 TI - An audit cycle of consent form completion: A useful tool to improve junior doctor training. AB - BACKGROUND: Consent for surgical procedures is an essential part of the patient's pathway. Junior doctors are often expected to do this, especially in the emergency setting. As a result, the aim of our audit was to assess our practice in consenting and institute changes within our department to maintain best medical practice. METHODS: An audit of consent form completion was conducted in March 2013. Standards were taken from Good Surgical Practice (2008) and General Medical Council guidelines. Inclusion of consent teaching at a formal consultant delivered orientation programme was then instituted. A re-audit was completed to reassess compliance. RESULTS: Thirty-seven consent forms were analysed. The re audit demonstrated an improvement in documentation of benefits (91-100%) and additional procedures (0-7.5%). Additional areas for improvement such as offering a copy of the consent form to the patient and confirmation of consent if a delay occurred between consenting and the procedure were identified. CONCLUSION: The re audit demonstrated an improvement in the consent process. It also identified new areas of emphasis that were addressed in formal teaching sessions. The audit cycle can be a useful tool in monitoring, assessing and improving clinical practice to ensure the provision of best patient care. PMID- 27274127 TI - Considerations for double-hand replantation in a resource-constrained healthcare facility. AB - Bilateral-hand amputation is extremely rare and double-hand replantation is even rarer. Only one case of successful double replantation at arm level has been reported from India. We present a case of double-hand replantation at proximal palmar level in a young adult executed in a small nursing home. The patient presented 5 h after injury with limbs preserved well in ice. There were difficulties in executing such an unusual case in a small nursing home set-up. The patient is performing his activities of daily living and basic functions independently. We share our experience of this double-hand replantation with special emphasis on problems encountered. PMID- 27274126 TI - Indigenous technique of fabricating vaginal mould for vaginal reconstruction and uterine drainage in McIndoe vaginoplasty using 10 ml syringe. AB - Absence of vagina poses multitude of physical and psychosocial problems in woman's life. 10% of Mayer- Rokitansky-uster-Hauser (MRKH) syndrome patients with high vaginal septum and vaginal atreisa has additional issue of draining uterine cavity. MC Indoe vaginoplasty is universally acceptable and widely practiced procedure for neocolposis reconstruction. Simultaneous reconstruction of vagina with simultaneous continued uterine drainage presents surgical challenge. We offer a simple solution of creating a vaginal mould using a 10 ml disposable syringe, which enables graft application of neovaginal cavity with simultaneous protected uterine drainage per vaginum. Total 10 patients were included in this study of which 4 needed uterine drainage procedure in addition to neovaginal creation. All the patients fared well, there were no problems regarding graft loss or vaginal mould extrusion etc. Fabrication of mould for graft enables easy dressing changes with out disturbing the skin graft. This innovation offers a simple easily reproducible and cheap way of fabricating vaginal mould for McIndoe vaginoplasty. It is especially useful for neovaginal graft application and simultaneous uterine drainage. PMID- 27274128 TI - Nerve sparing clitoroplasty in a rare case of idiopathic clitoromegaly. AB - Clitoromegaly is an embarrassing condition causing psychological stress, requiring intervention. The goals of clitoroplasty are to achieve normal genital anatomy and to preserve tactile sensation with a satisfactory sexual response. We present a rare case of idiopathic clitoromegaly managed by reduction clitoroplasty, preserving the dorsal neurovascular bundle and extensive network of nerves around the corpora to the glans and the creation of labia minora. PMID- 27274129 TI - Immediate breast reconstruction using the free lumbar artery perforator flap and lateral thoracic vein interposition graft for recipient lateral thoracic artery anastomosis. AB - The lumbar artery perforator (LAP) flap, which contains excess skin and fat tissue, love handles, that extends from the lower back to upper buttock, may provide an alternate tissue source for autologous breast reconstruction. However, LAP flap use during this procedure frequently requires vessel interposition grafts to correct the short flap pedicle length and mismatched recipient vessel calibre. A 46-year-old patient underwent a right nipple-sparing mastectomy using a lateral approach for ductal carcinoma in situ and immediate LAP flap breast reconstruction. The lateral thoracic vessel served as the recipient vessel, and a lateral thoracic vein interposition graft from the distal remnant was performed to adjust the arterial length and size discrepancy between the recipient lateral thoracic artery and pedicle artery. This procedure facilitates microsurgical anastomosis and medialisation of LAP flap to make a natural decollete line and create a cleavage for the reconstructed breast. PMID- 27274130 TI - Double free-flap for a bimalleolar defect of lower leg and ankle. AB - Double free-flaps are necessary when tissue cover cannot be sufficed with a single flap. The other factors to be considered when using two free flaps for resurfacing of distal limb defects are the availability of more than one recipient vessel, the risk of distal limb ischaemia and the donor site morbidity of double flap harvest. If these factors are adequately addressed, double free flaps can be safely executed for resurfacing distal limb defects with minimal morbidity. We report the simultaneous harvest and transfer of the anterolateral and anteromedial thigh flaps inset and vascularised as double free-flaps to resurface a large bimalleolar defect in a 14-year-old boy with no additional morbidity as compared to that of a single free tissue transfer. PMID- 27274131 TI - Successful microsurgical replantation of an amputated penis. AB - Penile amputation is an uncommon injury for which immediate surgical replantation is warranted. Microsurgical replantation is the "standard" method for penile replantation. Early replantation yields a high success and low complication rate. We report a case of a 34-year-old male who presented with amputation at the proximal penile shaft which was successfully replanted using microsurgical techniques. Minor skin necrosis was noted post-operatively which was debrided and covered with skin graft. Follow-up at 6 months showed satisfactory cosmetic appearance, normal voiding, return of sensations and erectile function. The level of evidence was V. PMID- 27274132 TI - Palatoglossal fusion with cleft palate and hypoplasia of cerebellar vermis. AB - A new-born male presented within 12 h of birth with respiratory distress. On examination and workup, he had palatoglossal fusion, cleft palate and hypoplasia of the cerebellar vermis. A 2.5 Fr endotracheal tube was inserted into the pharynx through nostril as a nasopharyngeal stent, following which his respiratory distress improved. Once child was optimised, then feeding was started by nasogastric tube and feeds were tolerated well. Elective tracheostomy and gastrostomy were done, followed by release of adhesions between the tongue and palate at a later stage. Review of literature suggests that palatoglossal fusion is uncommon and presents as an emergency. Mostly, these oral synechiae are associated with digital and/or cardiac anomaly. Other disorders associated with intra-oral synechiae include congenital alveolar synechiae, van der Woude syndrome, popliteal pterygium syndrome and oromandibular limb hypogenesis syndrome. The authors report a hitherto undescribed association of palatoglossal fusion with cleft palate and hypoplasia of the cerebellar vermis. PMID- 27274133 TI - Hand replantation: First experience in a sub-Saharan African country (Togo). AB - Fifty years after Chen has performed the first forearm replantation, we report our first case of hand replantation in a sub-Saharan African country. The etiology of the amputation was machete due to interpersonal violence. The amputation was trans-carpal, guillotine-type, subtotal non-viable maintained with a small skin bridge. The replantation procedure was successful. At one year follow-up, the functional result according to Chen's criteria was excellent. Through this first experience, we can state that hand replantation can be performed successfully both in survival and function in a non-specialized hospital of a sub-Saharan African country. PMID- 27274134 TI - Glial heterotopia of the lip: A rare presentation. AB - Glial heterotopia represents collections of normal glial tissue in an abnormal location distant to the central nervous system or spinal canal with no intracranial connectivity. Nasal gliomas are non-neoplastic midline tumours, with limited growth potential and no similarity to the central nervous system gliomas. The nose and the nasopharynx are the most common sites of location. Existence of glial heterotopia in the lip region is a rare developmental disorder. We report a case of large glial heterotopia in the upper lip region in a full-term female newborn which had intracranial extension with a fibrotic band. After the surgery, there was no recurrence in the follow-up period of 3 years. When glial heterotopia, which is a rare midline anomaly, is suspected, possible intracranial connection and properties of the mass should be evaluated by magnetic resonance imaging. By this way, lower complication rate and better aesthetic results can be achieved with early diagnosis and proper surgery. PMID- 27274135 TI - Hot-press hand injury caused by roller type ironing machine. AB - Thermal crush burn injury due to roller type ironing press machine is relatively rare and can cause destructive effects with significant morbidity. These injuries can be avoided by taking some basic precautions. Early debridement after admission and definitive treatment after the extent of injury are delineated and these are the preferred approaches in the management. We present a case of thermal crush injury of the hand caused by laundry roller type ironing press machine. PMID- 27274136 TI - Reinforcement of peritoneal repair in donor site post-concurrent laparotomy and rectus abdominis myocutaneous flap breast reconstruction using autologous dermal graft repair from zone 4 of deep inferior epigastric perforator flap: A case series in Asian patients. PMID- 27274138 TI - Smart apps for the smart plastic surgeon-An update. PMID- 27274137 TI - A cost-effective cadaveric model for plastic surgery simulation. PMID- 27274139 TI - Modified way of applying a tie-over dressing. PMID- 27274140 TI - An alternative receptacle for fat harvest: The infant mucous sucker. PMID- 27274141 TI - 'Glove technique' to secure skin grafts: A novel technique. PMID- 27274142 TI - Achieving optimal leg position for fibula flap harvest. PMID- 27274143 TI - Concern with the use of electrodes in perforator marking. PMID- 27274144 TI - Author's reply to comments on 'A simple technique of marking the perforator of a free flap for post-operative monitoring'. PMID- 27274145 TI - Index case of kite string causing neurovascular and tendon injury to ankle is being reported. PMID- 27274146 TI - Primary Dentition Analysis: Exploring a Hidden Approach. AB - BACKGROUND: Accurate prediction of the mesiodistal widths (MDWs) of canines and premolars in children with primary dentition facilitates interception of malocclusion at an early age. Boston University (BU) approach is one, i.e., based on primary teeth for predicting canine and premolar dimensions. AIM: To predict the canine and premolar dimensions, in the contemporary population, using BU approach and compare with the values obtained using Tanaka-Johnston (T/J) approach. DESIGN: Children in the age range of 7-11 years with presence of all permanent mandibular incisors and primary maxillary and mandibular canines and first molars were included in the study. Those with interproximal caries or restorations, abnormalities in shape or size and history of orthodontic treatment were excluded. Impressions of both arches were made using irreversible hydrocolloid and poured with dental stone. The MDWs of the required teeth were measured on the models using electronic digital vernier caliper from which widths of permanent canines and premolars were predicted using both T/J and BU approaches. RESULTS: Statistically significant (p = 0.00) positive correlation (r = 0.52-0.55) was observed between T/J and BU approaches. A statistically significant (p = 0.00) strong positive correlation (r = 0.72-0.77) was observed among girls, whereas boys showed a statistically nonsignificant weak positive correlation (r=0.17-0.42) based on gender. CONCLUSION: Boston University approach can be further studied prospectively to make it possible as a prediction method of permanent tooth dimensions for children in primary dentition stage. How to cite this article: Nuvvula S, Vanjari K, Kamatham R, Gaddam KR. Primary Dentition Analysis: Exploring a Hidden Approach. Int J Clin Pediatr Dent 2016;9(1):1-4. PMID- 27274147 TI - Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography. AB - OBJECTIVE: The aim of our study is to use cone beam computed tomography (CBCT) to assess the dimensional changes in the nasopharyngeal soft-tissue characteristics in children of Indian origin with repaired cleft lip and palate (CLP) and to compare the results with patients with ideal occlusion. MATERIALS AND METHODS: A sample of 20 children (10 girls, 10 boys) with repaired CLP was selected. Cone beam computed tomography scans were taken to measure the nasopharyngeal airway changes in terms of linear measurements and sagittal cross-sectional areas. Error analysis was performed to prevent systematic or random errors. Independent means t-tests and Pearson correlation analysis were used to evaluate sex differences and the correlations among the variables. RESULTS: Nasopharyngeal soft-tissue characteristics were different in the control and the study groups. Subjects with repaired CLP had lesser lower aerial width, lower adenoidal width and lower airway width. The upper airway width was also significantly lesser. The retropalatal and the total airway area were significantly greater in the control group. CONCLUSION: The narrow pharyngeal airway in patients with CLP might result in functional impairment of breathing in patients. Further investigations are necessary to clarify the relationship between pharyngeal structure and airway function in patients with CLP. How to cite this article: Agarwal A, Marwah N. Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography. Int J Clin Pediatr Dent 2016;9(1):5-9. PMID- 27274148 TI - Ability of Pit and Fissure Sealant-containing Amorphous Calcium Phosphate to inhibit Enamel Demineralization. AB - AIM: To evaluate the effect of amorphous calcium phosphate (ACP)-containing pit and fissure sealant on inhibition of enamel demineralization in vitro. MATERIALS AND METHODS: Enamel specimens (n = 75) were prepared using freshly extracted noncarious human third molars. Box-shaped cavities (8 * 2 * 2 mm) on the buccal or lingual surfaces were prepared and restored with resin-based sealant (ConciseTM), ACP-containing sealant (Aegis(r)) or fluoride-containing sealant (Conseal-FTM). The samples were acid challenged in a demineralizing solution of 50 mmol/l lactic acid at pH 5.0 for 4 days. The change in enamel microhardness (ASuH) was calculated. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey's post hoc test. RESULTS: The mean SuH0 (+/-SD) (in Vicker's unit) prior to the acid challenge was: ConciseTM (318.83 +/- 33.86), Aegis(r) (331.03 +/- 21.52), Conseal-FTM (310.12 +/- 34.31). Following the acid challenge, the values dropped in all groups and ASuH (+/-SD) values were 269.17 +/- 47.49, 151.39 +/- 23.96 and 175.79 +/- 32.39 respectively. CONCLUSION: The ACP containing pit and fissure sealant has the potential to inhibit enamel demineralization. How to cite this article: Zawaideh FI, Owais AI, Kawaja W. Ability of pit and fissure sealant-containing amorphous calcium phosphate to inhibit enamel demineralization. Int J Clin Pediatr Dent 2016;9(1):10-14. PMID- 27274149 TI - Effect of Comprehensive Dental Rehabilitation on Growth Parameters in Pediatric Patients with Severe Early Childhood Caries. AB - BACKGROUND: Children who have severe early childhood caries (S-ECC) weigh significantly less than caries-free children. The association between S-ECC and weight suggests that its timely treatment at early stages may preserve general health, in addition to preventing pain and infection. OBJECTIVE: This study was conducted to evaluate whether children with untreated S-ECC had lower weight and height as compared with children with low caries and to evaluate whether full mouth rehabilitation of children with S-ECC resulted in the phenomenon of catch up growth. MATERIALS AND METHODS: The weight and height of children with noncontributory medical histories and S-ECC (3-6 years) were compared with caries free children, before and 6 months after full mouth dental rehabilitation. RESULTS: Prior to dental rehabilitation, children with S-ECC had significantly less weight and height than their comparison counterparts (p < 0.001). Following therapeutic intervention, the test group children exhibited catch-up growth in relation to weight, as there was no significant difference in the body weight of the test and control groups (p = 0.171). CONCLUSION: Comprehensive full mouth rehabilitation of children with S-ECC results in catch-up growth, thus improving the overall health of the child. How to cite this article: Sachdev J, Bansal K, Chopra R. Effect of Comprehensive Dental Rehabilitation on Growth Parameters in Pediatric Patients with Severe Early Childhood Caries. Int J Clin Pediatr Dent 2016;9(1):15-20. PMID- 27274150 TI - Effect of 95% Ethanol as a Final Irrigant before Root Canal Obturation in Primary Teeth: An in vitro Study. AB - BACKGROUND: Successful obturation in the primary teeth demands complete dryness of the root canal system. AIM: The purpose of this study was to determine the effect of 95% ethanol as the final irrigant before root canal obturation in primary teeth. MATERIALS AND METHODS: A total of 20 extracted primary mandibular canines were biomechanically prepared and pre-obturated volume of each tooth was assessed using spiral computed tomography (CT). The specimens were divided into two groups (n = 10): group 1, Metapex group; group 2, zinc oxide eugenol group. Each group was further divided randomly into two subgroups (n = 5): subgroup 1, canals were dried with 95% ethanol; subgroup 2, canals were blot dried with paper points with the last one appearing dry. All canals were obturated and the postobturated volume of each tooth was measured. The percentage of obturated volume (POV) was calculated using the formula: (postobturated volume/preobturated volume) * 100. The POV between the groups was statistically analyzed using Mann Whitney test and Wilcoxon Signed rank test appropriately. RESULTS: Root canals that were dried with ethanol showed better obturation than using paper points alone and the difference was statistically significant in both group 1 (p < 0.001) and group 2 (p < 0.002). CONCLUSION: Drying of the root canal system with 95% ethanol can result in better obturation in the primary teeth. How to cite this article: Thiruvenkadam G, Asokan S, John B, Geetha Priya PR. Effect of 95% Ethanol as a Final Irrigant before Root Canal Obturation in Primary Teeth: An in vitro Study. Int J Clin Pediatr Dent 2016;9(1):21-24. PMID- 27274151 TI - Antimicrobial Efficacy of Probiotic and Herbal Oral Rinses against Candida albicans in Children: A Randomized Clinical Trial. AB - BACKGROUND: A growing number of dentists are embracing the philosophy that natural agents are better for children's oral health. Knowledge of probiotics on host immune system has entered a new phase of research, and progression in this field is likely to offer novel means by modulating host immunity for prevention and treatment of a wide variety of oral diseases. AIM: To compare the antimicrobial efficacy of probiotics in reducing salivary Candida albicans counts with commonly used antimicrobial agents like 0.2% chlorhexidine and herbal rinse. MATERIALS AND METHODS: A randomized clinical trial was conducted on 60 subjects aged between 6 and 14 years, for a period of 9 months. The subjects were randomly divided into three groups comprising 20 subjects in each group. Three oral agents were administered twice daily for a maximum period of 1 week. Candida albicans counts were recorded before and after intervention and the results were submitted for statistical analysis using Statistical Package for the Social Sciences (SPSS) version 15.0 software. RESULTS: The change in mean log10 colony-forming unit (CFU)/ ml of C. albicans in groups A to C was 0.43 +/- 0.72, 0.68 +/- 1.05 and 0.22 +/- 0.66 CFU/ml respectively. CONCLUSION: Data obtained from the study demonstrated that probiotic rinse was equally effective as 0.2% chlorhexidine digluconate rinse in reducing C. albicans counts after 1 week of intervention. Herbal oral rinse was least effective. Probiotic oral rinses have opened new horizons in improvement of oral health by maintaining healthy ecosystem. However, a longitudinal study with larger sample size needs to be undertaken to evaluate the therapeutic effects of probiotics and herbal agents. How to cite this article: Mishra R, Tandon S, Rathore M, Banerjee M. Antimicrobial Efficacy of Probiotic and Herbal Oral Rinses against Candida albicans in Children: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2016;9(1):25-30. PMID- 27274152 TI - Impact of Dental Health Education on "Specific Learning Needs" Children. AB - INTRODUCTION: This article compares and evaluates the effect of dental health education through schoolteachers and dental health professionals to "specific learning needs" children attending special school. MATERIALS AND METHODS: A total of 71 "specific learning needs" children attending special school participated in the study. The baseline oral hygiene index-simplified (OHI-S) for all the participants was recorded. The training of schoolteachers was done using audiovisual and verbal methods on dental health facts and how to provide instructions on oral hygiene measures for reinforcing to the students. The students were randomly divided into three groups: Group 1 - No further dental health education by the schoolteachers or by the dental professionals was given to these students after the initial oral health education. Group 2 - In this group, the trained teachers taught students about the importance of oral health and demonstrated them brushing technique at intervals of 15 days, 1 month and 3 months. Group 3 - The dental professionals imparted dental health education and also demonstrated brushing techniques to these students at intervals of 15 days, 1 month and 3 months. Six months following the intervention a second examination was done to find out the OHI-S scores. Data analysis were done with Statistical Packages for the Social Sciences (SPSS) version 16 using one-way analysis of variance (ANOVA) statistical test. RESULTS: Group 2 demonstrated significant decline in OHI-S scores after intervention and all the three groups showed a statistically significant difference between the baseline OHI-S score and the scores after 6 months. CONCLUSION: Schoolteachers can be utilized for reinforcing dental health education among "specific learning needs" children effectively. How to cite this article: Relwani AH, Kiran S, Bhatt R, Patel M. Impact of Dental Health Education on "Specific Learning Needs" Children. Int J Clin Pediatr Dent 2016;9(1):31-34. PMID- 27274153 TI - Effect of Chewing Bicarbonate-containing Sugar-free Gum on the Salivary pH: An in vivo Study. AB - The objective of the study was to evaluate the effect of chewing gum on the salivary pH and to compare the effect of chewing bicarbonate-containing sugar free gum on salivary pH against that of standard sugar-free gum. The experiment was carried out on 30 volunteers aged 20-22 years (mean age = 21 years) who fulfilled the inclusion criteria. The test gum was sugar-free greenmint-flavored bicarbonate-containing gum and the standard control was sugar-free spearmint flavored gum. The pH was measured immediately using pH strips. According to statistical analysis, the mean salivary pH of the bicarbonate gum at 0, 5, 10, 15 and 20 minutes is 6.9713, 6.5667, 6.4267, 6.3867 and 6.3233 respectively. There is decrease in pH from 0 to 20 minutes. According to Bonferroni, there was no significant difference in pH from 0 to 20 minutes, 10 to 20 minutes and 15 to 20 minutes, but there was a significant difference in salivary pH from 5 to 20 minutes (p = 0.014). The mean salivary pH of the standard gum at 0, 5, 10, 15 and 20 minutes is 6.8767, 6.6067, 6.4200, 6.4027 and 6.3000 respectively. There is decrease in pH from 0 to 20 minutes. According to Bonferroni, there was no significant difference in pH from 0 to 20 minutes, 5 to 20 minutes, 10 to 20 minutes and 15 to 20 minutes. Thus, the higher salivary pH achieved with chewing bicarbonate gum compared with a standard sugar-free gum may have important oral health implications. How to cite this article: Ballal RK, Bhat SS, Ramdas SS, Ballal S. Effect of Chewing Bicarbonate-containing Sugar-free Gum on the Salivary pH: An in vivo Study. Int J Clin Pediatr Dent 2016;9(1):35-38. PMID- 27274154 TI - Association of Dermatoglyphic Peculiarities with Dental Caries in Preschool Children of Lucknow, India. AB - BACKGROUND: Dermatoglyphics refers to study of the intricate dermal ridge configurations on the skin covering the palmar and plantar surfaces of hand and feet. The basis of considering dermatoglyphic patterns as genetic marker for dental caries is that the epithelium of finger buds as well as enamel has ectodermal origin, and both develop at the same time of intrauterine life. AIM: To assess the relationship between fingerprint patterns and dental caries among preschool children of Lucknow city. STUDY DESIGN: This study was of cross sectional design. MATERIALS AND METHODS: The study group comprised 512 preschool children 2-6 years of age. The prevalence of caries was recorded using "Dentition status and treatment needs" (WHO basic oral health assessment form, 1997). They were divided into three groups as follows: Group I (dmft score = 0-2), group II (dmft score = 3-4) and group III (dmft score >=5). The handprints of each child were taken using a stamp pad. The fingertip patterns were analyzed according to the classical method and were classified according to the topological method. The frequency of occurrence of type of dermatoglyphic pattern on fingertip of each digit was noted. STATISTICS: Chi-square test was used to test the significant difference in proportions. Means were compared using Student's t-test and analysis of variance (ANOVA) or F-test. RESULTS: Subjects belonging to groups II and III showed maximum occurrence of whorl pattern on all digits. Group I subjects had maximum occurrence of arch pattern. All the variables had statistically significant value, with a degree of divergence of specific dermatoglyphic patterns among all three groups. CONCLUSION: The dental caries susceptibility of an individual increased with incidence of whorl pattern and it decreased with incidence of arch pattern. How to cite this article: Singh E, Saha S, Jagannath GV, Singh S, Saha S, Garg N. Association of Dermatoglyphic Peculiarities with Dental Caries in Preschool Children of Lucknow, India. Int J Clin Pediatr Dent 2016;9(1):39-44. PMID- 27274155 TI - Reciprocating vs Rotary Instrumentation in Pediatric Endodontics: Cone Beam Computed Tomographic Analysis of Deciduous Root Canals using Two Single-file Systems. AB - BACKGROUND: Primary root canals are considered to be most challenging due to their complex anatomy. "Wave one" and "one shape" are single-file systems with reciprocating and rotary motion respectively. The aim of this study was to evaluate and compare dentin thickness, centering ability, canal transportation, and instrumentation time of wave one and one shape files in primary root canals using a cone beam computed tomographic (CBCT) analysis. STUDY DESIGN: This is an experimental, in vitro study comparing the two groups. MATERIALS AND METHODS: A total of 24 extracted human primary teeth with minimum 7 mm root length were included in the study. Cone beam computed tomographic images were taken before and after the instrumentation for each group. Dentin thickness, centering ability, canal transportation, and instrumentation times were evaluated for each group. RESULTS: A significant difference was found in instrumentation time and canal transportation measures between the two groups. Wave one showed less canal transportation as compared with one shape, and the mean instrumentation time of wave one was significantly less than one shape. CONCLUSION: Reciprocating single file systems was found to be faster with much less procedural errors and can hence be recommended for shaping the root canals of primary teeth. How to cite this article: Prabhakar AR, Yavagal C, Dixit K, Naik SV. Reciprocating vs Rotary Instrumentation in Pediatric Endodontics: Cone Beam Computed Tomographic Analysis of Deciduous Root Canals using Two Single-File Systems. Int J Clin Pediatr Dent 2016;9(1):45-49. PMID- 27274156 TI - Prevalence of Malocclusion among 10-12-year-old Schoolchildren in Kozhikode District, Kerala: An Epidemiological Study. AB - BACKGROUND: A malocclusion is an irregularity of the teeth or a malrelationship of the dental arches beyond the range of what is accepted as normal. OBJECTIVES: To determine the prevalence of malocclusion in children aged 10-12 years in Kozhikode district of Kerala, South India. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted among schoolchildren aged 10-12 years in six schools in Kozhikode district of Kerala, South India. A total of 2,366 children satisfied the inclusion criteria. Occlusal characteristics like crossbite, open bite, deep bite, protrusion of teeth, midline deviations, midline diastema and tooth rotation were recorded. The data were tabulated and analyzed using Chi square test. RESULTS: The results revealed that the overall prevalence of malocclusion was 83.3%. Of this, 69.8% of the children had Angle's class I malocclusion, 9.3% had class II malocclusion (division 1 = 8.85%, division 2 = 0.5%) and 4.1% had class III malocclusion; 23.2% showed an increased overjet (>3 mm), 0.4% reverse overjet, 35.6% increased overbite (>3 mm), 0.29% open bite, 7.2% crossbite with 4.6% crossbite of complete anterior teeth, 63.3% deviation of midline, 0.76% midline diastema and 3.25% rotated tooth. No significant differences in gender distributions of malocclusions were noted except for increased overjet and overbite. CONCLUSION: There is high prevalence of malocclusion among schoolchildren in Kozhikode district of Kerala. Early interception and early correction of these malocclusions will eliminate the potential irregularities and malpositions in the developing dentofacial complex. How to cite this article: Narayanan RK, Jeseem MT, Kumar TVA. Prevalence of Malocclusion among 10-12-year-old Schoolchildren in Kozhikode District, Kerala: An Epidemiological Study. Int J Clin Pediatr Dent 2016;9(1):50-55. PMID- 27274157 TI - Knowledge and Awareness of Primary Teeth and Their Importance among Parents in Bengaluru City, India. AB - INTRODUCTION: Often people responsible for the oral care of children feel or believe that since primary teeth will eventually shed, it is not worthwhile to spend time/money on providing good oral health to children. Parents are the ones who take care of their children and make decisions for them. Hence, they should have knowledge about primary teeth, their health and caring in order to build confidence in their children through tiny teeth. AIM: To assess the knowledge of primary teeth and their importance among parents with children below 12 years. MATERIALS AND METHODS: A total of 1,000 questionnaires containing questions written both in English and in the local language (Kannada) were prepared for data collection and were personally distributed to parents visiting dental clinics for their children's dental treatment. STATISTICAL ANALYSIS: Both descriptive statistics and Chi-square test were used. RESULTS: Complaints related to dental caries constituted 82% of children visiting dental clinics among children in Bengaluru city. Only 39% of respondents were aware of all functions of primary teeth. CONCLUSION: The present study revealed that the parents of Bengaluru city had superficial or partial knowledge of primary teeth and that there is a need to improve this awareness. How to cite this article: Setty JV, Srinivasan I. Knowledge and Awareness of Primary Teeth and Their Importance among Parents in Bengaluru City, India. Int J Clin Pediatr Dent 2016;9(1):56-61. PMID- 27274158 TI - Awareness in Primary School Teachers regarding Traumatic Dental Injuries in Children and Their Emergency Management: A Survey in South Jaipur. AB - INTRODUCTION: Trauma to primary and permanent teeth and their supporting structures is one of the most common dental problems seen in children. The prognosis of traumatized teeth depends on timely attention with prompt and appropriate treatment, which often relies on knowledge of the teachers who may be present at the place of accidents. Thus, the aim of this study was to evaluate via a questionnaire the knowledge level of primary school teachers in South Jaipur regarding dental trauma. DESIGN: Questionnaire survey. MATERIALS AND METHODS: A self-designed questionnaire was administered to 300 primary school teachers from 20 randomly selected private and semi-aided schools of South Jaipur. RESULTS: A total of 278 teachers responded to the survey. The collected data were subjected to statistical analysis. It was found that most of the respondents had accepted poor knowledge regarding dental trauma, with a mean knowledge of 10.56 +/- 2.58. CONCLUSION: This study highlighted inadequate knowledge regarding emergency management of traumatic dental injuries, and teachers felt the need for training in the management of dental trauma as part of their training program. How to cite this article: Nirwan M, Syed AA, Chaturvedi S, Goenka P, Sharma S. Awareness in Primary School Teachers regarding Traumatic Dental Injuries in Children and Their Emergency Management: A Survey in South Jaipur. Int J Clin Pediatr Dent 2016;9(1):62-66. PMID- 27274159 TI - Pendulum Therapy of Molar Distalization in Mixed Dentition. AB - Early and timely pedo-orthodontic treatment is aimed at eliminating the disturbances of skeletal or dentoalveolar development, to harmonize the stomatognathic system before the full eruption of all permanent teeth. The advantages of pendulum appliance are its minimal dependence on patient's compliance (child cooperation), ease of fabrication, onetime activation and adjustment of the springs if necessary to correct minor transverse and vertical molar positions. This article reports a successful treatment method of class II malocclusion with pendulum appliance in mixed dentition phase. Distalization of maxillary molar was done, followed by guidance of canine impaction orthodontically and other dental correction using 0.022 MBT appliances. Posttreatment results were stable and remarkable. How to cite this article: Patil RU, Prakash A, Agarwal A. Pendulum Therapy of Molar Distalization in Mixed Dentition. Int J Clin Pediatr Dent 2016;9(1):67-73. PMID- 27274160 TI - Agenesis of Permanent Mandibular Central Incisors: A Concordant Condition in Siblings. AB - Concordance is an identical expression of phenotype in two related individuals. Concordance expression of hypodontia is an uncommon condition where associated individuals are affected with exactly similar kind and number of missing teeth. There is very limited documentation of this condition either in twins or in siblings, and literature shows paucity of data with regard to this anomaly. To the best of our knowledge, there is only one such case reported in the literature, which has actually showed similar missing lower central incisors in siblings. This report presents a case of two girl siblings aged 11 and 13 years with congenital bilateral missing of permanent mandibular central incisors, which is an absolute concordant condition. Apart from discussing etiology, clinical implications and management, this article highlights the significance of concordant and discordant condition of hypodontia and expression of this condition in twins and siblings. How to cite this article: Kagitha PK, Namineni S, Tupalli AR, Challa SK. Agenesis of Permanent Mandibular Central Incisors: A Concordant Condition in Siblings. Int J Clin Pediatr Dent 2016;9(1):74-77. PMID- 27274161 TI - A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B. AB - Aglossia is a rare congenital malformation that often occurs as an isolated disorder or is observed in association with other congenital deformities, particularly limb defects. We present a unique case of a 7-year-old girl with aglossia, hypodactyli, rudimentary ears, retrognathic and V-shaped mandible. Her parental history revealed intrauterine exposure of medicines. The patient had problems in difficulty in eating, speech, taste sensation and hearing. The present case does not fit into Hall's classification of oromandibular limb hypogenesis syndrome (OLHS) which best describes hypoglossia and limb deformities. Therefore, the purpose of this article is to document the rare variant of OLHS which can be included in Hall's classification. How to cite this article: Kalaskar RR, Godhane A, Kalaskar A, Demble S. A Rare Clinical Variant of Oromandibular Limb Hypogenesis Syndrome Type I B. Int J Clin Pediatr Dent 2016;9(1):78-81. PMID- 27274162 TI - Hypothyroidism and Sturge-Weber Syndrome associated with Bilateral Port-wine Nevus. AB - Sturge-Weber syndrome (SWS) is a rare, nonhereditary developmental condition that is characterized by a hamartomatous vascular proliferation of the brain, resulting in multiple angiomas that occur on the same side due to arteriovenous malformations. It is believed to be caused by persistence of a vascular plexus around the cephalic portion of the neural tube and is present at birth in about 1 in every 50,000 babies. It is one of the phakomatoses which is often associated with port-wine stains (PWSs) of the face, glaucoma, seizures, mental retardation and ipsilateral leptomeningeal angioma. Many people with SWS probably never know they have it. Hypothyroidism is a condition that arises from inadequate release of thyroid-stimulating hormone to stimulate an otherwise normal thyroid gland. This condition is often associated with a deficient secretion of other pituitary hormone, and growth hormone deficiency occurs with an increased prevalence in SWS, presumably secondary to involvement of the hypothalamic-pituitary axis. Diagnosis is made by the presence of a facial PWS and evidence of leptomeningeal angioma either by skull X-ray or computed tomography scan that shows intracranial calcifications. Presently, there is no specific treatment for SWS, and the management of the clinical manifestations and complications is still far from adequate. Here, we report the case of hypothyroidism associated with SWS with oral and facial manifestations in an 11-year-old boy. How to cite this article: Saroj G, Gangwar A, Dhillon JK. Hypothyroidism and Sturge-Weber Syndrome associated with Bilateral Port-wine Nevus. Int J Clin Pediatr Dent 2016;9(1): 82 85. PMID- 27274163 TI - Space Maintenance with an Innovative "Tube and Loop" Space Maintainer (Nikhil Appliance). AB - Despite the best efforts in prevention, premature loss of primary teeth continues to be a common problem in pediatric dentistry, resulting in disruption of arch integrity and adversely affecting the proper alignment of permanent successors. Space maintainers (SMs) are special appliances used for maintaining space created due to premature loss of primary teeth. Band and loop SM is mostly indicated for the premature loss of single primary molar, but this appliance has a number of limitations both for operators and for patients. Presented in this article is an innovative "Tube and Loop" SM (Nikhil appliance) which offers several advantages over the conventional band and loop SM. It is not only easy and quick to fabricate but can also be completed in a single sitting and cumbersome steps like impression making and laboratory procedures namely soldering are eliminated. How to cite this article: Srivastava N, Grover J, Panthri P. Space Maintenance with an Innovative "Tube and Loop" Space Maintainer (Nikhil Appliance). Int J Clin Pediatr Dent 2016;9(1):86-89. PMID- 27274164 TI - Review of Dilaceration of Maxillary Central Incisor: A Mutidisciplinary Challenge. AB - Traumatic injuries to primary dentition may interfere with the development of permanent dentition. Among the many malformations, dilaceration is particularly important to the clinician. Management of dilacerated maxillary central incisor requires a multidisciplinary approach. The main purpose of this review is to present the etiological factors, the mechanism, clinical features, radiographic features and treatment of dilaceration of the maxillary central incisors. How to cite this article: Walia PS, Rohilla AK, Choudhary S, Kaur R. Review of Dilaceration of Maxillary Central Incisor: A Multidisciplinary Challenge. Int J Clin Pediatr Dent 2016;9(1):90-98. PMID- 27274165 TI - Uremic Toxins - Novel Arrhythmogenic Factor in Chronic Kidney Disease - Related Atrial Fibrillation. AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia. Chronic kidney disease (CKD) is associated with a high prevalence of AF, and uremic toxins are an important risk factor for cardiovascular diseases associated with CKD. Uremic toxins can produce pro-fibrotic, pro-hypertrophic, and pro-inflammatory effects on cardiac tissues and enhance oxidative stress or neurohormonal phenomena of cardiovascular injury, which are recognized as arrhythmogenic factors of AF. This article reviews the clinical, molecular, and electrophysiological data of uremic toxins in CKD considered to induce AF through multiple mechanisms on structural and electrical remodeling of the cardiovascular system. PMID- 27274166 TI - Acute Type A Aortic Dissection Presenting as ST-Segment Elevation Myocardial Infarction Referred for Primary Percutaneous Coronary Intervention. AB - BACKGROUND: When acute aortic dissection is complicated with acute myocardial infarction, the diagnosis of dissection can be problematic. In these cases, patients might be treated with primary percutaneous coronary intervention (PCI) and suffer acatastrophic outcome. However, there are few reports or algorithm to facilitate the accurate management of this clinical situation. METHODS: We evaluated 385 consecutive patients who underwent primary PCI arising from an initial diagnosis of STEMI at our hospitalbetween January 2006 and March 2011. Clinical characteristics, coronary angiographic findings, and outcomes were obtained from medical charts and databases. RESULTS: Five patients (1.3%) with STEMI secondary to aortic dissection were identified. All patients (100%) had sudden-onset of chest pain and a history of hypertension without diabetes or hyperlipidemia. An increased resistance while advancing the diagnostic catheter was reported by the operators in 3 of 5 patients (60%). Aortography performed by manual contrast-medium injection showed the discrepancy in the diameter between the aortic root and the ascending aorta in 4 patients (100%), and ascending aortic intimal flap dissections were noted in 3 patients (75%). Alternating appearance and disappearance of the coronary artery ostium was observed in 2 patients, and bedside echocardiography showed intimal flap extension inall 4 patients (100%) who underwent this examination. The mortality rate at 30days was 40%. CONCLUSIONS: We construct an algorithm that incorporated factors including careful history evaluation, bedside echocardiography, resistance encountered while advancing a catheter, and findings of aortography performed with manual injection,which could b evaluable for this clinical situation. PMID- 27274167 TI - Direct Adsorption of Anti-CD34 Antibodies on the Nano-Porous Stent Surface to Enhance Endothelialization. AB - BACKGROUND: In-stent restenosis following the insertion of conventional drug eluting stent has become an extremely serious problem due to coating techniques, with polymer matrices used to bind biological ingredients to the stent surface. However, several studies have indicated that new pro-healing technique could prevent stent thrombosis that can be caused by conventional drug-eluting stents. METHODS: A novel method of attaching anti-CD34 antibodies directly on the porous surface of a 316L stainless steel bare metal stent was developed in this study, which achieved both high stability of attached anti-CD34 antibodies on the metal stent surface and high antibody activity for stem cell capture. RESULTS: The in vitro and in vivo experimental results indicated that the new stent with directly coupled anti-CD34 antibodies can efficiently enhance stent endothelialization. CONCLUSIONS: This study indicates that we have developed a unique method of attaching anti-CD34 antibodies directly on the porous surface of a 316L stainless steel bare metal stent, which provides a novel polymer-free approach for developing pro-healing stents. PMID- 27274168 TI - Psychosocial Stress and Risk of Myocardial Infarction: A Case-Control Study in Belgrade (Serbia). AB - BACKGROUND: The purpose of this study was to investigate which psychosocial risk factors show the strongest association with occurrence of myocardial infarction (MI) in the population of Belgrade in peacetime, after the big political changes in Serbia. METHODS: A case-control study was conducted involving 154 consecutive newly diagnosed patients with MI, and 308 controls matched by gender, age, and place of residence. RESULTS: According to conditional logistic regression analysis, after adjustment for conventional coronary risk factors, the odds ratios (95% confidence intervals) for work-related stressful events, financial stress, deaths and diseases, and general stress were 3.78 (1.83-7.81), 3.80 (1.96 7.38), 1.69 (1.03-2.78), and 3.54 (2.01-6.22), respectively. Among individual stressful life events, the following were independently related to MI: death of a close family member, 2.21 (1.01-4.84); death of a close friend, 42.20 (3.70 481.29); major financial problems, 8.94 (1.83-43.63); minor financial problems, 4.74 (2.02-11.14); changes in working hours, 4.99 (1.64-15.22); and changes in working conditions, 30.94 (5.43-176.31). CONCLUSIONS: During this political transition period , stress at work, financial stress, and stress in general as they impacted the population of Belgrade, Serbia were strongly associated with occurence of MI. PMID- 27274169 TI - Influenza Vaccination Reduces Hospitalization for Heart Failure in Elderly Patients with Chronic Kidney Disease: A Population-Based Cohort Study. AB - BACKGROUND: Elderly patients with chronic kidney disease (CKD) are at a higher risk of hospitalization for cardiovascular diseases (CVD). Previous studies have reported the beneficial effects of the influenza vaccine in patients with CVD. However, the effects of influenza vaccination on the reduction of hospitalizations for heart failure (HF) in elderly patients with CKD remain unclear. METHODS: This cohort study comprised elderly patients (>= 55 years of age) with a recorded diagnosis of CKD (n = 4406) between January 1, 1999 and December 31, 2008. Each patient was followed-up until the end of 2008. The hazard ratio (HR) and 95% confidence interval (CI) for the association between the influenza vaccination and the first HF hospitalization were analyzed. In addition, the patients were categorized into four groups based on their vaccination status (unvaccinated and total number of vaccinations: 1, 2-3, and >= 4). RESULTS: We found that elderly patients with CKD receiving influenza vaccination exhibited a lower risk of HF hospitalization (adjusted HR, 0.31; 95% CI, 0.26-0.39, p < 0.001). The protective effects of influenza vaccination remained consistent regardless of the age group (55-64, 65-74, >= 75), sex, and influenza seasonality. When the patients were stratified according to the total number of vaccinations, the adjusted HRs for HF hospitalization were 0.60 (0.47 0.77), 0.30 (0.23-0.41), and 0.10 (0.06-0.16) for patients who received 1, 2-3, and >= 4 vaccinations during the follow-up period, respectively. CONCLUSIONS: The results revealed that elderly patients with CKD receiving annual influenza vaccination are at a lower risk of HF hospitalization. PMID- 27274171 TI - Predictive Value of Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Patients with Coronary Slow Flow. AB - BACKGROUND: Increased microvascular resistance due to chronic inflammation is assumed to be one of the mechanisms associated with coronary slow flow (CSF). Previous studies have shown that the platelet-to-lymphocyte ratio (PLR) and the neutrophil-lymphocyte ratio (NLR) are markers of inflammation for various diseases. In this study we aimed to evaluate the relationship between CSF and PLR NLR. METHODS: Seventy-eight patients with CSF and 50 patients with normal coronary flow were enrolled into this study. The study subjects underwent medical examination and testing, after which their platelet-to-lymphocyte ratios and NLR values were calculated. An independent observer measured the coronary flow rate by Thrombolysis in Myocardial Infarction Frame Count (TFC) method. The platelet to-lymphocyte ratio and NLR values were compared between the groups and correlation analysis was performed to explore the relationship between mean TFC with PLR and NLR. RESULTS: Platelet-to-lymphocyte ratio and NLR values were significantly higher in patients with CSF (p < 0.001). There was a positive significant correlation between TFC with NLR and PLR (Spearman's Rho: 0.59, p < 0.001 and Spearman's Rho: 0.30, p = 0.001, respectively). Multivariate logistic regression analysis revealed that NLR is the one independent predictor for CSF. CONCLUSIONS: This study demonstrated an association between CSF and PLR-NLR. Although the exact mechanism could not be explained, our findings support the possible role of inflammation in CSF physiopathology. PMID- 27274170 TI - Pulmonary Hypertension in Hemodialysis Patients Following Repeated Endovascular Thrombectomy. AB - BACKGROUND: The prevalence of pulmonary hypertension is unusually high in Taiwanese patients with end-stage renal disease. Thrombosis of hemodialysis grafts is common and pulmonary embolism has been reported after endovascular thrombectomy. The aim of this study was to evaluate the relationship between pulmonary hypertension and endovascular thrombectomy of hemodialysis grafts. METHODS: One hundred and ten patients on hemodialysis via arteriovenous grafts were enrolled in our study. The mean pulmonary artery pressure (PAP) was measured by right heart catheterization. Clinical information was collected by review of medical records. Comorbid cardiopulmonary disease was evaluated by echocardiography and chest X-ray. The history of patient vascular access thrombosis was reviewed from database, hemodialysis records, and interviews with staff at hemodialysis centers. RESULTS: Fifty-two participants (47%) had pulmonary hypertension diagnosed by right heart catheterization. There was no difference in the number of thrombectomy procedures between patients with and without pulmonary hypertension. Based on multivariate analysis, the number of prior endovascular thrombectomy procedures did not correlate with mean PAP (F value = 1.10, p = 0.30) nor was it associated with pulmonary hypertension (odds ratio = 0.92, p = 0.17). CONCLUSIONS: Prior endovascular arteriovenous graft thrombectomies were not associated with pulmonary hypertension or increased mean PAP in end-stage renal disease patients on maintenance hemodialysis. PMID- 27274172 TI - Assessment of Prognostic Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Patients with Pulmonary Embolism. AB - BACKGROUND: Acute pulmonary embolism is a serious medical condition that has a substantial global impact. Inflammation plays a role in the pathophysiology and prognosis of acute pulmonary embolism (APE). The aim of the present study was to investigate the prognostic value of admission parameters for complete blood count (CBC) in APE. METHODS: A total of 203 patients who were hospitalized with diagnosed APE were retrospectively enrolled in the study. Clinical data, PESI scores, admission CBC parameters, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were all recorded. The clinical outcomes of study subjects were determined by the reported patient 30-day mortality and long term mortality. RESULTS: During a median follow-up period of 20 months [interquantile range 17], 34 subjects in the study population (17%) died. NLR and PLR levels were significantly higher in patients who died within the 30 days (n = 14) [9.9 (5.5) vs. 4.5 (4.1), p = 0.01 and 280 (74) vs. 135 (75), p = 0.01, respectively] and during the long-term follow-up (n = 20) [8.4 (2.9) vs. 4.1 (3.8), p = 0.01 and 153 (117) vs. 133 (73), p = 0.03, respectively] when compared to the patients that survived. In Cox regression analysis, age, systolic blood pressure, systolic pulmonary arterial pressure, PESI scores (HR 1.02 95%CI 1.01 1.04, p = 0.01), elevated levels of NLR (HR 1.13 95%CI 1.04-1.23, p = 0.01) and PLR (HR 1.002 95%CI 1.001-1.004, p = 0.01) were independently correlated with total mortality. CONCLUSIONS: Admission NLR and PLR may have prognostic value in patients with APE. PMID- 27274173 TI - Antiplatelet Effect of Sequential Administration of Cilostazol in Patients with Acetylsalycilic Acid Resistance. AB - BACKGROUND: Acetylsalicylic acid (ASA) resistance in patients with coronary artery disease is an important medical problem that can affect treatment decision making and outcomes. Cilostazol has been investigated to determine its effectiveness in patients with acetylsalicylic acid resistance. The aim of this study was to evaluate the antiplatelet efficacy of sequential administration of CLZ in patients with ASA resistance. METHODS: A total of 180 patients were enrolled in our study. Patients with stable coronary artery disease were first given orally ASA 100 for 10 days, followed by collagen/epinephrine induced closure time (CTCEPI) measurements. Those who were found to be resistant to orally 100 mg of ASA were given orally 300 mg of ASA for an additional 10 days after which we repeated CTCEPI measurements. Those patients with resistance to orally 300 mg ASA were then given CLZ at a daily dose of orally 200 mg for 10 days followed by a final CTCEPI measurement. RESULTS: The rate of resistance to 100 mg ASA was 81/180 (45%) compared to a rate of 35/81 (43.2%) with 300 mg ASA. Of the 35 patients found to be resistant to 300 mg ASA, 22 (62.9%) also failed to respond to CLZ treatment. Overall, sequential administration of 300 mg ASA and 200 mg CLZ resulted in a reduction in the number of non-responders from 45% to 12.2%. CONCLUSIONS: Initiation of CLZ could be of benefit in some patients with ASA-resistance for whom an effective anti-aggregant effect is of clinical importance. PMID- 27274174 TI - Chest Pain with Normal Thallium-201 Myocardial Perfusion Image - Is It Really Normal? AB - BACKGROUND: Thallium-201 myocardial perfusion image (MPI) is commonly used to detect coronary artery disease in patients with chest pain. Although a normal thallium-201 MPI result is generally considered to be a good prognosis and further coronary angiogram is not recommended, there are still a few patients who suffer from unexpected acute coronary events. The aim of this study was to investigate the clinical prognosis in patients with normal thallium-201 MPI. METHODS: From January 2006 to August 2012, a total 22,003 patients undergoing thallium-201 MPI in one tertiary center were screened. Of these, 8092 patients had normal results and were investigated retrospectively. During follow-up, 54 patients underwent coronary angiogram because of refractory typical angina pectoris or unexpected acute coronary events. These 54 patients were divided into 2 groups: group I consisted of 26 (48.1%) patients with angiography-proven significant coronary artery stenosis, and group II consisted of 28 (51.9%) patients without significant stenosis. RESULTS: Patients in group I had a higher prevalence of prior coronary stenting and electrocardiographic features of ST depression compared with patients in group II. The multivariate analysis demonstrated that both prior coronary stenting and ST depression were risk predictors of unexpected acute coronary events in the patients with normal thallium-201 MPI [odds ratio (OR), 5.93; 95% confidence interval (CI): 1.03 34.06, p = 0.05 and OR, 7.10; 95% CI: 1.28-39.51, p = 0.03,respectively]. CONCLUSIONS: Although there is a low incidence of unexpected acute coronary events in patients with chest pain and normal thallium-201 MPI, physicians should be aware of the potentials risk in certain patients in this specific population. PMID- 27274175 TI - Risk Factors for Thrombosis, Overshunting and Death in Infants after Modified Blalock-Taussig Shunt. AB - BACKGROUND: The Modified Blalock-Taussig shunt procedure can provide increased flow of blood to the lungs for babies born with certain congenital heart defects. We evaluated 44 subjects under 2 years of age who had a Modified Blalock-Taussig shunt (MBTS) procedure performed from 2009-2013, to investigate risk factors for thrombosis, overshunting and death. METHODS: The study subjects included in our investigation were severely cyanotic newborns with pulmonary stenosis or atresia and duct dependent circulation, and infants having Tetralogy of Fallot with small pulmonary arteries who underwent a MBTS procedure in our facility from 2009-2013. We duly noted patient preoperative characteristics such as hemoglobin, hematocrit, mean platelet volume, prothrombin time and partial thromboplastin time. Our study investigated the risk factors for post-operative overcirculation, thrombosis and death. RESULTS: The age and weight of patients in our study at the time of procedure ranged from 1 day to 20 months old (median 12 days), and 2.4 kg to 12 kg (mean 4.6 kg), respectively. A total of 8 patients died following surgery, and. 4 (9.1%) had shunt thrombosis, of which one died during shunt revision. Partial thromboplastin time was 28.7 seconds in patients with thrombosis, and 35 in all other patients (p = 0.04). Overcirculation was detected in 5 patients; shunt size/body weight was 1.25 in patients who had overcirculation, and 1.06 in all other patients. CONCLUSIONS: It is important to assess risk factors associated with the MBTS operation. The results of our study suggest that a preoperative low aPTT value may be an indicator for thrombosis in infants who have undergone MBTS surgery. PMID- 27274177 TI - Conjunction of Endocardial and Coronary Venous System Mapping to Ablate Ventricular Arrhythmias. AB - BACKGROUND: Ablation of idiopathic ventricular arrhythmias (VAs) with epicardial or intramural origins is technically challenging. Herein, we have described the successful ablation of left VAs via the coronary venous system (CVS) in conjunction with endocardial map guided by three-dimensional electroanatomical map in six patients. METHODS: Out of a total consecutive 84 patients with symptomatic idiopathic VAs, radiofrequency ablation via the CVS was performed on six patients (7%). Furthermore, we reviewed patient records and electrophysiologic studies with respect to clinical characteristics. RESULTS: Activation map was conducted in 5 patients, and the earliest activation sites were identified within the CVS. The preceding times to the onset of QRS complex were longer than those at the earliest endocardial sites (36.2 +/- 5.6 ms vs. 14.2 +/- 6.4 ms, p = 0.02, n = 5). Spiky fractionated long-duration potentials were recorded at the successful ablation sites in all 5 patients. The other patient received pacemapping only because of few spontaneous VAs during the procedure, and the best pacemap spot was found within the CVS. Irrigated catheters were required in 4 out of 6 patients because VAs were temporarily suppressed with regular ones. CONCLUSIONS: Idiopathic VAs can be ablated via the CVS in conjunction with endocardial mapping. Additionally, spiky fractionated long-duration potential can function as a clue to identify the good ablation site. PMID- 27274178 TI - Echocardiographic Diagnosis of Incidentally Found Left Coronary Artery to Pulmonary Artery Fistula in an 11-Year-Old Girl. AB - We report on a healthy 11-year-old girl who presented to our facility with sudden onset of fainting in a strenuous running course. Transthoracic echocardiography at short-axis view showed a diastolic flow into the main pulmonary artery (PA). The diagnosis of left anterior descending artery (LAD) to PA fistula was documented by cardiac computed tomography and catheterization. Interventional therapy of LAD to the main PA fistula was not performed because of no evidence of myocardial ischemia or significant hemodynamic change. Presently, the patient remains asymptomatic. Coronary fistula with an incidence of about 0.1-0.8% is very rare and may be undetected, particularly in pediatric patients without cardiac murmur. We herein describe the diagnostic approach and discuss the current treatment modalities. PMID- 27274176 TI - Short and Long-Term Effect of Carotid Artery Stenting on Arterial Blood Pressure Measured through Ambulatory Blood Pressure Monitoring. AB - BACKGROUND: The aim of this study was to assess the short and long-term effects of carotid artery stenting (CAS) procedure on blood pressure (BP) through ambulatory BP monitoring. METHODS: One hundred fifty three patients who underwent CAS for primary or secondary protection from December 2010 to September 2013 were enrolled to our study. The BP levels of total of 123 patients were monitored for 1 year. Thereafter, the pre-procedure levels of BP were compared with BP levels at the 24-hour and the first year intervals after the procedure. RESULTS: Systolic and diastolic BP levels at the 24-hour and the first year intervals after CAS were significantly lower than the pre-procedure BP levels. The mean 24 hour systolic BP was 113 +/- 13 mmHg and diastolic BP was 63 +/- 8 mmHg, both of which were significantly lower (p < 0.001 and p < 0.001 respectively), while the pre-procedure mean systolic BP was 133 +/- 10 mmHg and the mean diastolic BP was 75 +/- 9 mmHg. Moreover, the mean first-year systolic BP was 125 +/- 10 mmHg with a decline of 8 +/- 8 mmHg and mean diastolic BP was 71 +/- 8 mmHg with a decline of 4 +/- 7 mmHg, both of which were again significantly lower compared to the pre procedure levels (p < 0.001 and p < 0.001 respectively). CONCLUSIONS: The results of our study suggested that systolic and diastolic BP levels diminished after CAS. Additionally, BP reduction continued even 1 year after the CAS. PMID- 27274179 TI - Side-Branch and Coaxial Intravascular Ultrasound Guided Wire Re-Entry after Failed Retrograde Approach of Chronic Total Occlusion Intervention. AB - Intravascular ultrasound (IVUS) can provide valuable information during the intervention of difficult chronic total occlusion (CTO) lesion. Stumpless CTO lesions with an adjacent side branch are associated with a significantly lower success rate because the proper entry point is not always clearly identified and the guidewires easily slip into the side branch. Herein we presented a case of a stumpless middle left circumflex (LCX) artery CTO lesion with auto-collateral from obtuse marginal branch. Initially, we positioned the IVUS into the side branch to find the entry point of LCX-CTO lesion. However, the punctured wire went into the false lumen. A retrograde approach was tried but later failed. Therefore, we used IVUS to find the entry point where the true lumen transited to the false lumen, and used a stiff guidewire to puncture the entry point. After we confirmed with IVUS that the whole guidewire was in the true lumen, we deployed 3 drug-eluting stents. The final angiogram showed TIMI 3 flow with preservation of all side branches. The patient was angina-free during the 6-month follow-up. By presenting this case, we have demonstrated the application of both side-branch and coaxial IVUS-guided recanalization technique in the stumpless CTO lesion. PMID- 27274180 TI - Accidental Stenting Out of Stent: A Lesson from No-Reflow after New Stent Deployment Outside the Prior Stent. AB - An operator can be unaware that the guide wire has accidentally advanced into space outside the previous stent, which can result in deformation of the previous stent when a new stent is deployed outside the prior stent. We herein have reported a case of accidental guide wire advancement into a previously dissected lumen of right coronary artery (RCA), resulting in a new stent deploying outside the prior stent, resulting in deformity of the prior stent. Thrombus and friable atheromatous plaques dislodged and migrated to occlude distal RCA when attempting to restore the proximal luminal diameter by balloon inflation, resulting in profound shock with asystole. IVUS was successful in identifying the cause, and the thrombus was removed successfully by manual aspiration. Due to the poor endothelization of a recent stenting, clinicians should be particularly careful of possible wire advancing outside the stent structure, which can result in prominent thrombus or atheromatous debris occluding the distal vessel, and IVUS may be useful in confirming the cause of no-reflow. PMID- 27274181 TI - Percutaneous Closure of an Iatrogenic Aorta to Right Ventricle Fistula Acquired Following Intracardiac Repair. AB - Iatrogenic aortocardiac fistulae have been described rarely following intracardiac repair. This 28 year-old-male presented to our facility with dyspnea going on 20 days after closure of ventricular septal defect (VSD) and resection of subaortic membrane. A communication was noticed between the aorta and the right ventricle (RV) upon transthoracic echocardiography. Cardiac catheterisation revealed a significant shunt and an aortogram revealed a 6 mm communication between aorta and right ventricle. Percutaneous closure of this defect was attempted under local anaesthesia through right femoral access. An alpha arteriovenous loop was formed despite repeated attempts, hence a retrograde approach for device delivery was considered. An 8 mm Amplatzer muscular VSD occluder device was deployed across the defect achieving a complete closure through an 8F delivery sheath. To the best of our knowledge this is the first report of an iatrogenic aorta to RV fistula occurring in a patient following an intracardiac repair which has been successfully treated percutaneously. PMID- 27274183 TI - Uterine Perforation with Intra-Abdominal Clostridium perfringens Gas Gangrene: A Rare and Fatal Infection. AB - Background:Clostridium perfringens gas gangrene is an extremely rare and fatal infection. Necrosis of the myometrium is rarely seen and has only been recorded in 18 cases to date. Of these 18 reported cases, only 5 have occurred in nonpregnant women. This article presents the 6th case of myometrium necrosis from C. perfringens.Case: A 72-year-old woman, gravida 2, para 2, presented with abdominal pain and vaginal bleeding. After examinations, laboratory testing, and several surgical interventions, she was found to have C. perfringens infection and advanced high-grade serous adenocarcinoma of the endometrium with >50% invasion into the myometrium. Results: Despite the surgical interventions and use of several antibiotics, this patient did not improve. She was weaned from treatment per her advance directive and died after weaning. Conclusions: Awareness of the many etiologies for peritonitis is of great importance when a fatal infection may be the cause of the condition. Correct diagnosis and proper treatment is essential for the survival of patients infected with C. perfringens. (J GYNECOL SURG 32:182). PMID- 27274182 TI - The Impact of Obesity on Surgical Outcome in Endometrial Cancer Patients: A Systematic Review. AB - Background: Obesity is a significant public health problem in the United States, and many studies have established obesity as a significant risk factor for endometrial cancer. Surgery is the standard of care in staging and treatment of endometrial cancer, and obesity may influence surgical outcomes because of its attendant comorbid conditions. Therefore, assessment of the impact of obesity on surgical outcome is important for decreasing morbidity and improving survival in patients with endometrial cancer. Objective: The aims of this research were to evaluate and review epidemiologic data systematically on the impact of obesity on surgical outcomes and to assess safety and feasibility of newer surgical techniques in obese patients. Materials and Methods: A systematic search of PubMed was conducted to identify articles between 2004 and 2013 that focused on the impact of obesity on surgical outcome. Reference lists of retrieved articles were also used to identify other relevant articles. Thirteen relevant articles were reviewed. Results: Evidence from epidemiologic studies showed that obesity impacts surgical outcome adversely. On average, obese patients have worse surgical outcomes than their nonobese counterparts. In addition, surgical outcome worsens as level of obesity increases. However, surgical procedure also influences this association. Minimally invasive surgeries are more useful and are accompanied with fewer complications than conventional laparotomy and can be performed safely in obese patients. Conclusions: Obesity is a significant risk in the etiology, treatment, and surgical outcomes of patients with endometrial cancer. Future research will need more randomized controlled trials and prospective studies to identify the best procedures for maximal outcomes. (J GYNECOL SURG 32:149). PMID- 27274184 TI - Comparison of visual outcomes and subjective visual quality after bilateral implantation of a diffractive trifocal intraocular lens and blended implantation of apodized diffractive bifocal intraocular lenses. AB - PURPOSE: To compare the visual acuity (VA) and quality of vision between bilateral implantation of a trifocal intraocular lens (IOL) and blended bifocal IOLs with an intermediate add in the dominant eye and a near add in the nondominant eye. PATIENTS AND METHODS: Patients with either trifocal or blended bifocal IOLs implanted were recruited after surgery. Subjects returned for a single diagnostic visit between 3 and 24 months after surgery. VA was tested at various distances, including low-contrast acuity and acuity at their preferred reading distance. A binocular defocus curve was obtained, and subjective visual function and quality of vision were evaluated. RESULTS: Twenty-five trifocal subjects and 30 blended bifocal subjects were enrolled. There were no significant differences in low-contrast acuity, preferred reading distance, or acuity at that reading distance. Binocular vision at 4 m, 60 cm, and 40 cm was not statistically significantly different. The trifocal provided statistically significantly better visual acuity (P<0.05) at vergences from -0.5 to -1.5 D (from 2 m to 67 cm viewing distance, P<0.05). There was no statistically significant difference in the near vision subscale scores of the 39-question National Eye Institute Visual Function Questionnaire or the overall scores of the Quality of Vision questionnaire, though significantly more trifocal subjects reported that the observed visual disturbances were "bothersome" (P<0.05). CONCLUSION: Both lens modalities provided subjects with excellent binocular near and distance vision, with similar low rates of visual disturbances and good reported functional vision. The trifocal IOL provided significantly better intermediate VA in the viewing distance range of 2 m to 67 cm, corresponding to viewing things such as a car dashboard or grocery shelf. VA was similar between groups at viewing distances from 60 to 40 cm, corresponding to computer or reading distance. PMID- 27274185 TI - A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome. AB - PURPOSE: To evaluate the efficacy of oral antioxidant supplementation in the treatment of patients with dry eye syndrome (DES). METHODS: A prospective, randomized, double-blinded study compared the effects of an antioxidant supplement (containing anthocyanosides, astaxanthin, vitamins A, C, and E, and several herbal extracts, including Cassiae semen and Ophiopogonis japonicus) with placebo on patients with DES. We assessed dry eye symptoms, visual acuity, Schirmer's test, tear film breakup time, cornea and conjunctiva fluorescein staining, serum anti-SSA/anti-SSB antibodies, and the level of reactive oxygen species (ROS) in tears. The supplementation period was 8 weeks and patients were followed up every 4 weeks for 16 weeks. A linear mixed model was used to compare the groups, while within-group differences were tested by repeated-measures analysis of variance. RESULTS: Forty-three patients, 20 and 23 in treatment and placebo groups, respectively, completed the study. Liver and renal functions were normal. Diastolic blood pressure decreased in the treatment group. There were no significant differences in systolic blood pressure, dry eye symptoms, serum anti SSA and anti-SSB, visual acuity, intraocular pressure, or fluorescein corneal staining between the groups. Tear film breakup time scores and Schirmer's test without topical anesthesia significantly improved in the treatment group. Tear ROS level differed between the groups and decreased after treatment. Overall subjective impression revealed a significant improvement with treatment compared with placebo. CONCLUSION: Oral antioxidant supplementations may increase tear production and improve tear film stability by reducing tear ROS. The vegetable based antioxidant supplement used in this study is safe and can be utilized as an adjuvant therapy to conventional artificial tear therapy for patients with DES. PMID- 27274186 TI - Effect of benzalkonium chloride-free latanoprost ophthalmic solution on ocular surface in patients with glaucoma. AB - INTRODUCTION: Benzalkonium chloride (BAK), included as a preservative in many topical treatments for glaucoma, induces significant toxicity and alters tear breakup time (TBUT). BAK-containing latanoprost, an ester prodrug of prostaglandin F2alpha, can cause ocular adverse events (AEs) associated with BAK. The purpose of this study was to evaluate the efficacy and safety of BAK-free latanoprost. PATIENTS AND METHODS: A prospective, open-label, single-arm, multicenter, 8-week study in patients with primary open-angle glaucoma or ocular hypertension taking BAK-containing latanoprost for >=12 months was performed. Patients were switched to BAK-free latanoprost ophthalmic solution 0.005% administered once daily, and eyes were assessed after 28 and 56 days. Primary efficacy and safety variables were TBUT and treatment-emergent AEs, respectively. RESULTS: At day 56, 40 eyes were evaluable. Mean TBUT increased significantly from baseline (3.67+/-1.60 seconds) to 5.03+/-2.64 and 6.06+/-3.39 seconds after 28 and 56 days of treatment with BAK-free latanoprost (P<0.0001). Ocular Surface Disease Index((c)) (OSDI((c))) score also decreased significantly to 12.06+/ 13.40 and 7.06+/-10.75 at 28 and 56 days, respectively, versus baseline (18.09+/ 18.61, P<0.0001). In addition, inferior corneal staining score decreased significantly to 0.53 from baseline (0.85, P=0.0033). A reduction in conjunctival hyperemia and intraocular pressure was observed at both time points. No treatment related serious AEs were evident and 12 (26.08%) treatment-emergent AEs occurred in seven patients, with eye pain and irritation being the most frequent. No clinically significant changes in vital signs or slit lamp examinations were observed. CONCLUSION: Results indicate that switching from BAK-containing latanoprost to BAK-free latanoprost resulted in significant improvements in TBUT, OSDI((c)) score, and inferior corneal staining score, and measurable reductions in conjunctival hyperemia score. Furthermore, BAK-free latanoprost was well tolerated with only mild-to-moderate and self-limiting AEs. BAK-free latanoprost appears to be effective in protecting ocular surface integrity in glaucoma patients but further studies are needed to confirm this beneficial effect. PMID- 27274187 TI - Comparison of intraocular pressure adjusted by central corneal thickness or corneal biomechanical properties as measured in glaucomatous eyes using noncontact tonometers and the Goldmann applanation tonometer. AB - PURPOSE: To investigate the correlation coefficients between intraocular pressure (IOP) before and after adjusting for central corneal thickness (CCT) and corneal biomechanical properties. PATIENTS AND METHODS: A total of 218 eyes of 218 patients with primary open-angle glaucoma (mean age =71.5 years; mean spherical equivalent =-0.51 D; mean deviation determined by Humphrey visual field analyzer =-3.22 dB) were included in this study. The tIOP and tIOPCCT, which were adjusted by the CCT (with tIOP meaning IOP not adjusted by CCT, as determined using the CT 1P; and tIOPCCT meaning IOP adjusted by CCT, as determined using the CT-1P), were determined using a noncontact tonometer. The IOPg and IOPCCT, which were adjusted by CCT, and IOPcc adjusted by corneal biomechanical properties were determined using a Reichert 7CR (with IOPg meaning IOP not adjusted by CCT or corneal biomechanical properties, as determined using the Reichert 7CR; IOPCCT meaning IOP adjusted by CCT, as determined using the Reichert 7CR; and IOPcc meaning IOP adjusted by corneal biomechanical properties, as determined using the Reichert 7CR). The GT and GTCCT adjusted by CCT were determined using a Goldmann applanation tonometer (with GT meaning IOP not adjusted by CCT, as determined using the Goldmann applanation tonometer; and with GTCCT meaning IOP adjusted by CCT, as determined using the GAT). Pearson's correlation coefficients among the IOPs were calculated and compared. P-values <0.05 were considered as statistically significant. RESULTS: The tIOP, tIOPCCT, IOPg, IOPCCT, IOPcc, GT, and GTCCT were 14.8+/-2.5, 15.0+/-2.4, 13.1+/-3.2, 13.3+/-3.1, 13.7+/-2.9, 13.2+/ 2.4, and 13.4+/-2.3 mmHg (mean +/- standard deviation), respectively. The correlation coefficient between tIOPCCT and tIOP (r=0.979) was significantly higher than that between tIOPCCT and the other IOPs (r=0.668-0.852; P<0.001, respectively). The correlation coefficient between IOPCCT and IOPg (r=0.994) or IOPcc and IOPg (r=0.892) was significantly higher than that between IOPCCT or IOPcc and the other IOPs (r=0.669-0.740; P<0.001, respectively). The correlation coefficient between GTCCT and GT (r=0.989) was significantly higher than that between GTCCT and the other IOPs (r=0.669-0.740; P<0.001, respectively). CONCLUSION: The IOP adjusted by CCT or corneal biomechanical properties depends on the measurement instrument itself, rather than the adjustment methods, for eyes of patients with primary open-angle glaucoma. PMID- 27274188 TI - An exploratory study evaluating the effects of macular carotenoid supplementation in various retinal diseases. AB - PURPOSE: The aim of this study was to assess the impact of daily oral supplementation with Macushield (10 mg/d meso-zeaxanthin, 10 mg/d lutein, and 2 mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. METHODS: Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6 months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute- Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. RESULTS: A statistically significant increase in the MP optical density was observed using the dual wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P<0.05) improvements in glare sensitivity in low and medium spatial frequencies were observed at 3 months and 6 months. Ceiling effects confounded other visual function tests and quality of life changes. CONCLUSION: Supplementation with the three carotenoids enhances certain aspects of visual performance in retinal diseases. PMID- 27274189 TI - Pre- and postsynaptic effects of brimonidine on isolated rabbit iris dilator muscles. AB - PURPOSE: Brimonidine is an imidazoline compound used for the treatment of glaucoma, but having very little effect on pupil diameter. Like para aminoclonidine, most imidazoline compounds interact with postsynaptic alpha adrenoceptors and cause pupil dilatation. Therefore, as part of an investigation of the mechanism of action of brimonidine on pupil diameter, the present study was initiated to measure, in vitro, the relative potency of brimonidine on the pre- and postsynaptic alpha-adrenoceptors of rabbit iris dilator muscle. METHODS: The contractile activity of brimonidine and its effect on twitch contraction evoked by electrical field stimulation were studied in isolated rabbit iris dilator muscles by isometric tension recording. RESULTS: Brimonidine significantly inhibited the twitch contraction of the dilator muscle caused by field stimulation, without affecting the response to exogenously applied phenylephrine. Compared to phenylephrine, brimonidine caused only a small contractile response with % maximum contraction values of <10%. CONCLUSION: These results suggest that brimonidine may act on nerve endings to inhibit adrenergic neurotransmission with very little effect on postsynaptic alpha-adrenoceptors. This may indicate that brimonidine reduced the pupil diameter just a little, thus improving night vision. PMID- 27274190 TI - Ranibizumab in monotherapy and combined with photodynamic therapy for retinal angiomatous proliferation. AB - PURPOSE: To compare the effects of intravitreal ranibizumab in monotherapy (group A) and combined with photodynamic therapy (PDT) with verteporfin (group B) in retinal angiomatous proliferation (RAP) treatment. METHODS: This was a multicentric, prospective, randomized clinical study conducted with parallel groups. The study eye in both groups received ranibizumab on days 1, 30, and 60 (loading dose); group B received PDT additionally on day 1. Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) testing and optical coherence tomography were performed monthly, and fluorescein angiography and indocyanine green angiography were performed quarterly. Retreatment criteria were leakage in fluorescein angiography or indocyanine green angiography, mean foveal thickness increase >=100 um, or VA decrease >=5 letters. RESULTS: Twenty patients were recruited (ten patients in each group). Six eyes had previous treatment (three eyes in group A and three eyes in group B), so only 14 eyes were naive. At 12-month follow-up, mean VA improved +1.5 letters in group A and +5.6 letters in group B (analysis of variance test; P>0.05). Two patients (20%) in both groups gained >=15 letters (chi-square test; P>0.05). Mean changes in greatest linear dimension and in foveal thickness were not statistically significant between groups of treatment (analysis of variance test; P>0.05). Mean retreatments per patient were 1.8 (group A) and 0.9 (group B) (Mann-Whitney U-test; P>0.05). One patient died due to underlying disease not related to study medication. CONCLUSION: Intravitreal ranibizumab administered in monotherapy or combined with PDT was efficacious in terms of VA stabilization in patients with RAP. PMID- 27274191 TI - Time of maximum cycloplegia after instillation of cyclopentolate 1% in children with brown irises. AB - PURPOSE: We aimed to 1) determine the time of maximum cycloplegia after instillation of cyclopentolate 1% in children with brown irises, 2) evaluate the correlation between the pupillary reaction and time of maximum cycloplegia, and 3) identify any side effects of the medication. PATIENTS AND METHODS: This was a prospective analytical study involving children aged 5 to 14 years who were attending refraction clinic. Cyclopentolate 1% was instilled three times at 10 minute intervals. The spherical equivalent, pupillary reaction, and pupillary diameter were recorded before the first drop and nine times after the last drop at 10-minute intervals. Side effects were assessed. Time of maximum cycloplegia was determined from the time point at which the 95% confidence interval of the differences between the mean spherical equivalent at each point and its final value at 110 minutes was reached and remained within the equivalence limit (+/ 0.25 D). RESULTS: Sixty children were enrolled in this study. Their mean age was 9.8 years (range: 5-4 years). Time of maximum cycloplegia was reached at 30 minutes after the first instillation of cyclopentolate. A poor correlation was observed between the pupillary reaction and the time of maximum cycloplegia (r= 0.07). The mean pupillary diameter at 30 minutes was 3.7+/-1.3 mm, and further dilation occurred thereafter. No side effects were observed. CONCLUSION: In most children, maximum cycloplegia was reached 30 minutes after the first instillation of cyclopentolate. The absence of a pupillary reaction should not be used as an indicator of maximum cycloplegia. PMID- 27274193 TI - Omega-3 fatty acid supplementation improves dry eye symptoms in patients with glaucoma: results of a prospective multicenter study. PMID- 27274192 TI - Segmentation and removal of fibrovascular membranes with high-speed 23 G transconjunctival sutureless vitrectomy, in severe proliferative diabetic retinopathy. AB - AIM: To evaluate the effectiveness and safety of high-speed (5,000 cuts per minute) 23 G transconjunctival sutureless vitrectomy (TSV) in severe diabetic fibrovascular proliferation (DFVP). PATIENTS AND METHODS: In this retrospective consecutive case series, patients who underwent 23 G TSV for severe DFVP between October 2011 and March 2014 at our institution were evaluated. 23 G TSV was performed with a high-speed (5,000 cuts per minute) cutter without a chandelier light. RESULTS: The mean follow-up period was 8 months (range: 4-23 months). Of the 27 eyes of 27 patients, 14 eyes (52%) underwent concomitant phacoemulsification with posterior chamber intraocular lens implantation, nine eyes (33%) were pseudophakic, and four eyes were phakic (15%). DFVP was removed with ease in all, and visual acuity was improved in 18 (67%) eyes. Iatrogenic retinal tear was observed in four eyes (15%) and treated successfully during surgery. Suture placement to a single sclerotomy was performed in eight eyes (30%). Postoperative intraocular hemorrhage was observed in five eyes (18%). Cataract formation was observed in two of the four phakic eyes. Three (11%) patients had postoperative intraocular pressure rise. Postoperative hypotony (<=6 mmHg) and endophthalmitis were not observed in any eye. CONCLUSION: The segmentation and removal of fibrovascular membranes with high-speed 23 G TSV seems to be a safe and easy method in severe diabetic eye disease. PMID- 27274194 TI - Clinical utility of the KAMRA corneal inlay. AB - The treatment of presbyopia has been the focus of much scientific and clinical research over recent years, not least due to an increasingly aging population but also the desire for spectacle independence. Many lens and nonlens-based approaches have been investigated, and with advances in biomaterials and improved surgical methods, removable corneal inlays have been developed. One such development is the KAMRATM inlay where a small entrance pupil is exploited to create a pinhole-type effect that increases the depth of focus and enables improvement in near visual acuity. Short- and long-term clinical studies have all reported significant improvement in near and intermediate vision compared to preoperative measures following monocular implantation (nondominant eye), with a large proportion of patients achieving Jaeger (J) 2 to J1 (~0.00 logMAR to ~0.10 logMAR) at the final follow-up. Although distance acuity is reduced slightly in the treated eye, binocular visual acuity and function remain very good (mean 0.10 logMAR or better). The safety of the inlay is well established and easily removable, and although some patients have developed corneal changes, these are clinically insignificant and the incidence appears to reduce markedly with advancements in KAMRA design, implantation technique, and femtosecond laser technology. This review aims to summarize the currently published peer-reviewed studies on the safety and efficacy of the KAMRA inlay and discusses the surgical and clinical outcomes with respect to the patient's visual function. PMID- 27274195 TI - Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study. AB - BACKGROUND: HMS5552, a novel fourth-generation glucokinase (GK) activator, has demonstrated promising effects on glycemic control in preclinical models of type 2 diabetes. This single ascending dose study was conducted to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HMS5552 during its first-in-human exposure. METHODS: Sixty healthy subjects were enrolled. In each of six dose-cohorts (5, 10, 15, 25, 35, and 50 mg), ten subjects were randomized with eight subjects receiving the same cohort-dose of HMS5552 and two receiving placebo. Plasma HMS5552 exposure, glucose, and insulin were measured repeatedly during fasting and after a standardized meal. Assessment included safety, PK, and PD endpoints. RESULTS: HMS5552 showed dose-proportional increases in area under the curve 0 to the last quantifiable concentration (AUC0 t) and maximum plasma concentration (Cmax). Slopes estimated by linear regression for AUC0-t and Cmax were ~1.0 (0.932 and 0.933, respectively). Geometric mean elimination half-life ranged from 4.48 to 7.51 hours and apparent clearance ranged from 11.5 to 13.1 L/h across all doses. No significant sex effect was observed in PK parameters. HMS5552 also demonstrated dose-related PD responses in terms of maximum glucose change from baseline (%) and mean glucose area under effect curve 0-4 hours change from baseline (%) (P<0.001). Fifteen adverse events were reported by nine subjects (ten with HMS5552 and five with the placebo). All adverse events were mild in intensity and resolved without any treatment. CONCLUSION: This first-in-human single ascending dose study provided predicted PK of HMS5552 with dose-proportional increases in AUC0-t and Cmax, as well as dose related glucose-lowering effects over the range of 5-50 mg in healthy subjects. HMS5552 at doses up to 50 mg in healthy subjects was safe and well-tolerated. PMID- 27274197 TI - Spotlight on brexpiprazole and its potential in the treatment of schizophrenia and as adjunctive therapy for the treatment of major depression. AB - Antipsychotic agents, utilized for the treatment of a range of psychiatric disorders, differ substantially in terms of their pharmacology and adverse effect profiles. Incomplete and variable efficacy, differences in safety-tolerability, and highly heterogeneous response across individuals prompt development of new agents. Brexpiprazole is one of the two most recently introduced antipsychotic agents approved for the treatment of schizophrenia and as an adjunct for treatment of major depressive disorder. Its pharmacology, clinical trial data, and efficacy and side effects in comparison with other antipsychotic agents are discussed. Brexpiprazole is a dopamine D-2 partial agonist with potent activity at the serotonin 5HT1A and 5HT2A and noradrenergic alpha-1B and alpha-2C receptors. Placebo-controlled clinical trials in persons with schizophrenia support its efficacy in treating psychosis and preventing relapse. Short-term clinical trials also support its efficacy as an adjunct to antidepressants in treating major depressive disorder in individuals inadequately responsive to antidepressant treatment alone. Adverse effects include akathisia, gastrointestinal side effects, and moderate weight gain. The recommended oral dose of brexpiprazole is 2-4 mg/day in schizophrenia and 2-3 mg/day as adjunctive treatment in major depression. It must be titrated up to its target dose over 1-2 weeks and is effective in once-daily dosing. How brexpiprazole's unique pharmacological profile will translate into clinically meaningful differences from other antipsychotic agents is unclear. Its place in our antipsychotic armamentarium and potential role in the treatment of schizophrenia and major depressive disorder will be determined by additional clinical data and experience. PMID- 27274196 TI - Spotlight on valsartan-sacubitril fixed-dose combination for heart failure: the evidence to date. AB - Heart failure is a global problem with elevated prevalence, and it is associated with substantial cardiovascular morbidity and mortality. Treating heart-failure patients has been a very challenging task. This review highlights the main pharmacological developments in the field of heart failure with reduced ejection fraction, giving emphasis to a drug that has a dual-acting inhibition of the neprilysin and renin-angiotensin-aldosterone system. Neprilysin is an enzyme that participates in the breakdown of biologically active natriuretic peptides and several other vasoactive compounds. The inhibition of neprilysin has been a therapeutic target for several drugs tested in cardiovascular disease, mainly for heart failure and/or hypertension. However, side effects and a lack of efficacy led to discontinuation of their development. LCZ696 is a first-in-class neprilysin- and angiotensin-receptor inhibitor that has been developed for use in heart failure. This drug is composed of two molecular moieties in a single crystalline complex: a neprilysin-inhibitor prodrug (sacubitril) and the angiotensin-receptor blocker (valsartan). The PARADIGM-HF trial demonstrated that this drug was superior to an angiotensin-converting enzyme inhibitor (enalapril) in reducing mortality in patients with heart failure with reduced ejection fraction. The ability to block the angiotensin receptor and augment the endogenous natriuretic peptide system provides a distinctive mechanism of action in cardiovascular disease. PMID- 27274198 TI - The combination of blueberry juice and probiotics reduces apoptosis of alcoholic fatty liver of mice by affecting SIRT1 pathway. AB - PURPOSE: To explore the effects of the combination of blueberry juice and probiotics on the apoptosis of alcoholic fatty liver disease (AFLD). METHODS: Healthy C57BL/6J mice were used in the control group (CG). AFLD mice models were established with Lieber-DeCarli ethanol diet and evenly assigned to six groups with different treatments: MG (model), SI (SIRT1 [sirtuin type 1] small interfering RNA [siRNA]), BJ (blueberry juice), BJSI (blueberry juice and SIRT1 siRNA), BJP (blueberry juice and probiotics), and BJPSI (blueberry juice, probiotics, and SIRT1 siRNA). Hepatic tissue was observed using hematoxylin and eosin (HE) and Oil Red O (ORO) staining. Biochemical indexes of the blood serum were analyzed. The levels of SIRT1, caspase-3, forkhead box protein O1 (FOXO1), FasL (tumor necrosis factor ligand superfamily member 6), BAX, and Bcl-2 were measured by reverse transcription-polymerase chain reaction and Western blotting. RESULTS: HE and ORO staining showed that the hepatocytes were heavily destroyed with large lipid droplets in MG and SI groups, while the severity was reduced in the CG, BJ, and BJP groups (P<0.05). The levels of superoxide dismutase (SOD), reduced glutathione (GSH), and high-density lipoprotein-cholesterol (HDL-C) were increased in BJ and BJP groups when compared with the model group (P<0.05). In contrast, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total triglycerides (TGs), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and malondialdehyde (MDA) were lower in BJ and BJP groups than in the model group (P<0.05). The level of SIRT1 was increased, while the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase 3, BAX, and Bcl-2 were decreased in CG, BJ, and BJP groups (P<0.05). Meanwhile, SIRT1 silence resulted in increase of the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2. CONCLUSION: The combination of blueberry juice and probiotics reduces apoptosis in AFLD by suppressing FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2 via the upregulation of SIRT1. PMID- 27274199 TI - Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury. AB - BACKGROUND: Activators of PPARs, particularly PPARgamma, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA) may act as a PPARgamma agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance. METHODS: The middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours) was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARgamma antagonist) was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARgamma level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed. RESULTS: UA-treated (5, 10, or 20 mg/kg) rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P<0.01). Both the PPARgamma protein level and the percentage of PPARgamma-positive cells were increased in the UA treated groups (P<0.01). Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P<0.01) but an increased level of TIMP1 (P<0.01). UA exerted its protective effects in a dose dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARgamma expression; however UA continued to exert a significant but partial neuroprotective effect. CONCLUSION: UA can act as a PPARgamma agonist to improve the metalloprotease/anti metalloprotease balance, possibly by inhibiting the activation of the MAPK signaling pathway, thereby attenuating cerebral ischemia and reperfusion injury. Therefore, UA may serve as a novel neuroprotective therapeutic agent. PMID- 27274200 TI - Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension. AB - Pulmonary arterial hypertension is a progressive, debilitating disease caused by a dysregulation of the pulmonary vascular tone that inevitably leads to right heart failure and death without treatment. Until relatively recently, the treatment options for those afflicted by pulmonary arterial hypertension were limited; today, a greater understanding of the pathophysiology behind this disease has led to several evidence-based therapies that can improve pulmonary function and quality of life for these patients. One of the primary mediators of pulmonary vascular tone is endothelin-1, which is a potent and long-lasting vasoconstrictor. Macitentan is a second-generation endothelin receptor antagonist that acts selectively as a pulmonary vasodilator without the significant side effects noted with previous endothelin receptor antagonists. This review focuses on the mechanism of action and pharmacokinetics of macitentan, as well as the adverse effects, efficacy, and clinical uses of macitentan in the clinical trials to date. In addition, the authors briefly review clinical trials currently underway to illustrate possible future directions for the use of macitentan. PMID- 27274201 TI - Spotlight on idarucizumab and its potential for the reversal of anticoagulant effects of dabigatran. AB - Idarucizumab is the first targeted antidote of dabigatran, a direct oral anticoagulant used for prevention and treatment of venous thromboembolism and prevention of stroke in atrial fibrillation. Idarucizumab is a humanized fragment of a monoclonal antibody, which binds dabigatran reversibly with high affinity and, when administered intravenously, immediately neutralizes its anticoagulant effect. It is rapidly cleared by the kidney with captured dabigatran. In Phase I and II trials, no significant adverse events have been reported. Specifically, idarucizumab has no anticoagulant or procoagulant effect by itself. Idarucizumab is currently being evaluated in an ongoing Phase III trial, in patients treated with dabigatran presenting with severe active bleeding or requiring emergency surgery or an invasive procedure and are at high risk of bleeding. The results of the interim analysis confirm the ability of idarucizumab to neutralize dabigatran instantaneously, without rebound effect, except in rare patients with very high baseline levels of anticoagulant. Although not definitely proving clinical efficacy, due to the noncontrolled design of the trial and the heterogeneity of patient conditions, these promising results on an intermediate criterion with strong rationale have led to the approval of idarucizumab for these indications. However, several questions are unresolved. First, activity measurement of dabigatran in blood, useless in current practice, could be useful to guide the treatment and avoid over- or underutilization of the antidote; but so far, it has not been largely available in real time. Second, the translation of anticoagulant neutralization to an effect on mortality and better outcome is highly dependent on the global management of these patients, especially rapid diagnosis, supportive care, and easy access to antidote administration. Although idarucizumab represents a remarkable achievement in drug design and development, whether it will be an important step toward improved safety of patients treated with dabigatran in the real world will have to be demonstrated in the postmarketing phase. PMID- 27274202 TI - Reducing the trigger dose of recombinant hCG in high-responder patients attending an assisted reproductive technology program: an observational study. AB - Decreasing the dose of human chorionic gonadotropin (hCG) used to trigger final oocyte maturation in assisted reproductive technology programs is regarded as a useful intervention in the prevention of ovarian hyperstimulation syndrome, but the minimal effective dose has not been yet identified. In this study, the capacity of a reduced dose of recombinant hCG (r-hCG) to provide adequate oocyte maturation was tested for the first time. Thirty-five high-responder patients received a dose of 125 ug (half of the standard dose) of r-hCG for triggering final oocyte maturation. The number of oocytes retrieved per patient and the proportion of mature oocytes were evaluated. As a result, a mean number of 14 oocytes were retrieved, of which 85% were found to be mature (MII). There was only one patient developing a moderate form of ovarian hyperstimulation syndrome and not requiring hospitalization. It is suggested that r-hCG at 125 ug can be effective in triggering final oocyte maturation in high-responder patients. Additional properly powered and controlled studies are needed to support this contention. PMID- 27274204 TI - Older patients' experiences during care transition. AB - BACKGROUND: A fragmented health care system leads to an increased demand for continuity of care across health care levels. Research indicates age-related differences during care transition, with the oldest patients having experiences and needs that differ from those of other patients. To meet the older patients' needs and preferences during care transition, professionals must understand their experiences. OBJECTIVE: The purpose of the study was to explore how patients >=80 years of age experienced the care transition from hospital to municipal health care services. METHODS: The study has a descriptive, explorative design, using semistructured interviews. Fourteen patients aged >=80 participated in the study. Qualitative content analysis was used to describe the individuals' experiences during care transition. RESULTS: Two complementary themes emerged during the analysis: "Participation depends on being invited to plan the care transition" and "Managing continuity of care represents a complex and challenging process". DISCUSSION: Lack of participation, insufficient information, and vague responsibilities among staff during care transition seemed to limit the continuity of care. The patients are the vulnerable part of the care transition process, although they possess important resources, which illustrate the importance of making their voice heard. Older patients are therefore likely to benefit from more intensive support. A tailored, patient-centered follow-up of each patient is suggested to ensure that patient preferences and continuity of care to adhere to the new situation. PMID- 27274203 TI - Electroporation-delivered transdermal neostigmine in rats: equivalent action to intravenous administration. AB - PURPOSE: Transdermal electroporation has become one of the most promising noninvasive methods for drug administration, with greatly increased transport of macromolecules through the skin. The cecal-contracting effects of repeated transdermal electroporation delivery and intravenous administration of neostigmine were compared in anesthetized rats. METHODS: The cecal contractions were detected with implantable strain gauge sensors, and the plasma levels of neostigmine were followed by high-performance liquid chromatography. RESULTS: Both intravenously and EP-administered neostigmine (0.2-66.7 MUg/kg) increased the cecal contractions in a dose-dependent manner. For both the low doses and the highest dose, the neostigmine plasma concentrations were the same after the two modes of administration, while an insignificantly higher level was observed at a dose of 20 MUg/kg after intravenous administration as compared with the electroporation route. The contractile responses did not differ significantly after the two administration routes. CONCLUSION: The results suggest that electroporation-delivered neostigmine elicits action equivalent to that observed after intravenous administration as concerning both time and intensity. Electroporation permits the delivery of even lower doses of water-soluble compounds through the skin, which is very promising for clinical practice. PMID- 27274205 TI - Typology of end-of-life priorities in Saudi females: averaging analysis and Q methodology. AB - BACKGROUND: Understanding culture-and sex-related end-of-life preferences is essential to provide quality end-of-life care. We have previously explored end-of life choices in Saudi males and found important culture-related differences and that Q-methodology is useful in identifying intraculture, opinion-based groups. Here, we explore Saudi females' end-of-life choices. METHODS: A volunteer sample of 68 females rank-ordered 47 opinion statements on end-of-life issues into a nine-category symmetrical distribution. The ranking scores of the statements were analyzed by averaging analysis and Q-methodology. RESULTS: The mean age of the females in the sample was 30.3 years (range, 19-55 years). Among them, 51% reported average religiosity, 78% reported very good health, 79% reported very good life quality, and 100% reported high-school education or more. The extreme five overall priorities were to be able to say the statement of faith, be at peace with God, die without having the body exposed, maintain dignity, and resolve all conflicts. The extreme five overall dis-priorities were to die in the hospital, die well dressed, be informed about impending death by family/friends rather than doctor, die at peak of life, and not know if one has a fatal illness. Q-methodology identified five opinion-based groups with qualitatively different characteristics: "physical and emotional privacy concerned, family caring" (younger, lower religiosity), "whole person" (higher religiosity), "pain and informational privacy concerned" (lower life quality), "decisional privacy concerned" (older, higher life quality), and "life quantity concerned, family dependent" (high life quality, low life satisfaction). Out of the extreme 14 priorities/dis-priorities for each group, 21%-50% were not represented among the extreme 20 priorities/dis-priorities for the entire sample. CONCLUSION: Consistent with the previously reported findings in Saudi males, transcendence and dying in the hospital were the extreme end-of-life priority and dis-priority, respectively, in Saudi females. Body modesty was a major overall concern; however, concerns about pain, various types of privacy, and life quantity were variably emphasized by the five opinion-based groups but masked by averaging analysis. PMID- 27274206 TI - Attitudes toward anticoagulant treatment among nonvalvular atrial fibrillation patients at high risk of stroke and low risk of bleed. AB - BACKGROUND: Atrial fibrillation (AF) is associated with an increased risk of stroke. Anticoagulant (AC) therapies are effective at treating AF, but carry with them an increased risk of bleed. Research suggests that a large proportion of AF patients who have high risk of stroke and low risk of bleeding are not currently receiving AC treatment. The goal of this study was to understand the reasons why these patients do not engage in this potentially life-saving treatment. METHOD: Through a self-report online survey, using validated instruments, 1,184 US adults who self-reported a diagnosis of AF were screened for the risk of stroke and bleed. Of these patients, 230 (19.4%) were at high risk of stroke, low risk of bleed, and not currently using an AC treatment, and were asked follow-up questions to assess their reasons for nontreatment, attitudes toward treatment, and attitudes toward dosing regimens. RESULTS: The most common reasons patients stopped AC treatment were concerns regarding bleeding (27.8%) and other medical concerns (26.6%), whereas the most common reason cited for not being prescribed an AC in the first place was the use of antiplatelet therapy as an alternative (57.1%). In both cases, potentially erroneous decisions regarding perceived stoke and/or bleeding risk were also a factor. Finally, the largest factors regarding attitudes toward treatment and dosing regimen were instructions from an authority figure (eg, physician, pharmacist) and ease of use, respectively. CONCLUSION: Results suggest that many AF patients who are at high risk of stroke but at low risk of bleed may not be receiving AC due to potentially inaccurate beliefs about risk. This study also found that AF patients place trust in physicians above other factors such as cost when making treatment decisions. Increased education of patients by physicians on the risks and benefits may be a simple strategy to improve outcomes. PMID- 27274207 TI - Impact of telephonic interviews on persistence and daily adherence to insulin treatment in insulin-naive type 2 diabetes patients: dropout study. AB - OBJECTIVE: The objective of this study is to evaluate the impact of sequential telephonic interviews on treatment persistence and daily adherence to insulin injections among insulin-naive type 2 diabetes patients initiated on different insulin regimens in a 3-month period. METHODS: A total of 1,456 insulin-naive patients with type 2 diabetes (mean [standard deviation, SD] age: 56.0 [12.0] years, 49.1% were females) initiated on insulin therapy and consecutively randomized to sequential (n=733) and single (n=723) telephonic interview groups were included. Data on insulin treatment and self-reported blood glucose values were obtained via telephone interview. Logistic regression analysis was performed for factors predicting increased likelihood of persistence and skipping an injection. RESULTS: Overall, 76.8% patients (83.2% in sequential vs 70.3% in single interview group, (P<0.001) remained on insulin treatment at the third month. Significantly higher rate for skipping doses was noted in basal bolus than in other regimens (27.0% vs 15.0% for premixed and 15.8% basal insulin, respectively, P<0.0001). Logistic regression analysis revealed sequential telephonic interview (odds ratio [OR], 1.531; 95% confidence interval [CI], 1.093 2.143; P=0.013), higher hemoglobin A1c levels (OR, 1.090; 95% CI, 0.999-1.189; P=0.049), and less negative appraisal of insulin therapy as significant predictors of higher persistence. Basal bolus regimen (OR, 1.583; 95% CI, 1.011 2.479; P=0.045) and higher hemoglobin A1c levels (OR, 1.114; 95% CI, 1.028-1.207; P=0.008) were the significant predictors of increased likelihood of skipping an injection. CONCLUSION: Our findings revealed positive influence of sequential telephonic interview, although including no intervention in treatment, on achieving better treatment persistence in type 2 diabetes patients initiating insulin. PMID- 27274208 TI - Development of TUA-WELLNESS screening tool for screening risk of mild cognitive impairment among community-dwelling older adults. AB - BACKGROUND AND AIM: Focus on screening for cognitive impairment has to be given particular importance because of the rising older adult population. Thus, this study aimed to develop and assess a brief screening tool consisting of ten items that can be self-administered by community dwelling older adults (TUA-WELLNESS). METHODOLOGY: A total of 1,993 noninstitutionalized respondents aged 60 years and above were selected for this study. The dependent variable was mild cognitive impairment (MCI) assessed using neuropsychological test batteries. The items for the screening tool comprised a wide range of factors that were chosen mainly from the analysis of ordinal logistic regression (OLR) and based on past literature. A suitable cut-off point was developed using receiver operating characteristic analysis. RESULTS: A total of ten items were included in the screening tool. From the ten items, eight were found to be significant by ordinal logistic regression and the remaining two items were part of the tool because they showed strong association with cognitive impairment in previous studies. The area under curve (AUC), sensitivity, and specificity for cut-off 11 were 0.84%, 83.3%, and 73.4%, respectively. CONCLUSION: TUA-WELLNESS screening tool has been used to screen for major risk factors of MCI among Malaysian older adults. This tool is only suitable for basic MCI risk screening purpose and should not be used for diagnostic purpose. PMID- 27274209 TI - Maximal intermittent handgrip strategy: design and evaluation of an exercise protocol and a grip tool. AB - Handgrip (HG) exercise has been prescribed as a lifestyle intervention to successfully reduce resting blood pressure (BP) among heterogeneous groups of participants. Current HG protocols have limited accessibility due to complicated exercise prescriptions and sophisticated required equipment. Therefore, this research describes the design and evaluation of the maximal intermittent (MINT) HG exercise strategy, consisting of both a novel exercise protocol (32*5 seconds maximal grip squeezes separated by 5 seconds of rest between sets) and an original grip tool. This research was a multistep progressive design that included 51 postmenopausal women as participants in three separate research studies. Part 1 of this research focuses on the MINT exercise protocol. A literature-informed rationale for the design of the protocol is described. This includes exercise intensity, work-to-rest ratio, and total exercise duration with reference to the unique physiology (mechanoreflex and metaboreflex) of postmenopausal women. Subsequent experimental analyses of acute responses to the MINT protocol revealed that women produced 50% of their maximum grip force with moderate cardiovascular responses (increases of systolic BP: 41.6 mmHg, diastolic BP: 20.1 mmHg, heart rate: 35.1 bpm) that remained far below the thresholds of concern identified by the American College of Sports Medicine. Part 2 of this research describes the creation of a novel grip tool, beginning with a mixed methods assessment of participant opinions regarding two distinct in-laboratory grip tools, leading to the creation of four prototype MINT tools. Structured focus groups revealed a strong preference for MINT prototype 1 for all tool design features, including color, shape, size, and foam grip. Collectively, the result of this multistep research is a novel HG exercise strategy with enhanced accessibility by being easy to understand and simple to execute. The long-term training effectiveness of MINT as an exercise intervention for the reduction of resting BP has yet to be determined. PMID- 27274210 TI - Neurocognitive testing and cochlear implantation: insights into performance in older adults. AB - OBJECTIVE: The aim of this case series was to assess the impact of auditory rehabilitation with cochlear implantation on the cognitive function of elderly patients over time. DESIGN: This is a longitudinal case series of prospective data assessing neurocognitive function and speech perception in an elderly cohort pre- and post-implantation. SETTING: University cochlear implant center. PARTICIPANTS: The patients were post-lingually deafened elderly female (mean, 73.6 years; SD, 5.82; range, 67-81 years) cochlear implant recipients (n=7). MEASUREMENTS: A neurocognitive battery of 20 tests assessing intellectual function, learning, short- and long-term memory, verbal fluency, attention, mental flexibility, and processing speed was performed prior to and 2-4.1 years (mean, 3.7) after cochlear implant (CI). Speech perception testing using Consonant-Nucleus-Consonant words was performed prior to implantation and at regular intervals postoperatively. Individual and aggregate differences in cognitive function pre- and post-CI were estimated. Logistic regression with cluster adjustment was used to estimate the association (%improvement or %decline) between speech understanding and years from implantation at 1 year, 2 years, and 3 years post-CI. RESULTS: Improvements after CI were observed in 14 (70%) of all subtests administered. Declines occurred in five (25%) subtests. In 55 individual tests (43%), post-CI performance improved compared to a patient's own performance before implantation. Of these, nine (45%) showed moderate or pronounced improvement. Overall, improvements were largest in the verbal and memory domains. Logistic regression demonstrated a significant relationship between speech perception and cognitive function over time. Five neurocognitive tests were predictive of improved speech perception following implantation. CONCLUSION: Comprehensive neurocognitive testing of elderly women demonstrated areas of improvement in cognitive function and auditory perception following cochlear implantation. Multiple neurocognitive tests were strongly associated with current speech perception measures. While these data shed light on the complex relationship between hearing and cognition by showing that CI may slow the expected age-related cognitive decline, further research is needed to examine the impact of hearing rehabilitation on cognitive decline. PMID- 27274211 TI - Density abnormalities in normal-appearing gray matter in the middle-aged brain with white matter hyperintense lesions: a DARTEL-enhanced voxel-based morphometry study. AB - BACKGROUND AND PURPOSE: Little is known about the structural alterations within gray matter (GM) in middle-aged subjects with white matter hyperintense (WMH) lesions. Here, we aimed to examine the anatomical changes within the GM and their relationship to WMH lesion loads in middle-aged subjects. PARTICIPANTS AND METHODS: Twenty-three middle-aged subjects with WMH lesions (WMH group) and 23 demographically matched healthy control subjects participated in the study. A Diffeomorphic Anatomical Registration Through Exponentiated Liealgebra-enhanced voxel-based morphometry was used to measure the GM density, and the correlations between WMH lesion volume and extracted GM values in abnormal regions were identified by voxel-based morphometry analysis. RESULTS: Compared with the healthy control subjects, the WMH group had a significantly decreased GM density in the left middle frontal gyrus, bilateral anterior cingulate cortex, left and right premotor cortex, and left and right middle cingulate cortex and an increased GM density in the bilateral cerebellum anterior lobe, left middle temporal gyrus, right temporoparietal junction, left and right prefrontal cortex (PFC), and left inferior parietal lobule. A relationship was observed between the normalized WMH lesion volume and the decreased GM density, including the left middle frontal gyrus (rho=-0.629, P=0.002), bilateral anterior cingulate cortex (rho=-0.507, P=0.019), right middle cingulate cortex (rho=-0.484, P=0.026), and right premotor cortex (rho=-0.438, P=0.047). The WMH lesion loads also negatively correlated with increased GM density in the right temporoparietal junction (rho= 0.484, P=0.026), left PFC (rho=-0.469, P=0.032), and right PFC (rho=-0.438, P=0.047). CONCLUSION: We observed that lesion load-associated structural plasticity corresponds to bidirectional changes in regional GM density in the WMH group. PMID- 27274212 TI - Fraction of exhaled nitric oxide measurements in the diagnoses of asthma in elderly patients. AB - OBJECTIVE: To assess the value of fraction of exhaled nitric oxide (FeNO) measurements in the diagnosis of asthma in elderly patients. METHODS: The clinical symptoms of 202 elderly patients were assessed with the asthma module of the International Study of Asthma and Allergies in Childhood test, which had been modified for the elderly patients, and the diagnostic routine for chronic obstructive pulmonary disease (COPD), which was based on the Global initiative for chronic Obstructive Lung Disease criteria. Of the 202 patients assessed, 43 were subjected to pulmonary function evaluations (spirometry) and FeNO measurements. RESULTS: Of the 202 elderly patients, 34 had asthma (23 definite and eleven probable), 20 met COPD criteria, 13 presented with an overlap of asthma and COPD, and 135 did not fit the criteria for obstructive pulmonary disease. Among the 43 elderly patients who were subjected to FeNO measurements, ten showed altered results (23.2%) and 33 had normal results (76.7%). The average value of FeNO in patients with definite and probable asthma undergoing this procedure was 29.2 parts per billion whereas that in nonasthmatic patients was 17.5 parts per billion (P=0.0002). CONCLUSION: We show a clear relationship between FeNO levels and asthma symptoms and previous asthma diagnoses in elderly patients. PMID- 27274213 TI - Safety and efficacy of phacoemulsification and intraocular lens implantation through a small pupil using minimal iris manipulation. AB - PURPOSE: The aim of this study was to compare the results of phacoemulsification through a small pupil using minimal iris manipulation versus phacoemulsification through a well-dilated pupil. METHODS: This prospective randomized control (comparative) study comprised 78 patients (group I) with a maximally dilated pupil size of <=4.00 mm and 45 patients (group II) with dilated pupil size of >=7.00 mm. In group I patients, only viscodilation and minimal push-and-pull iris stretching with two collar-button iris-retractor hooks were utilized without iris manipulation. Phacoemulsification was performed by two senior surgeons and the technique used consisted of either stop and chop or quick chop, infusion/aspiration of lens cortex, capsular bag refill with ocular viscoelastic devices, and implantation of an acrylic foldable intraocular lens. Patients were examined on the first day and 1 month postoperatively. RESULTS: Forty-six eyes of group I patients had pseudoexfoliation syndrome, eleven eyes had previous glaucoma surgery, 14 eyes had angle-closure or open-angle glaucoma, and seven eyes had posterior synechiae with iritis. In group I patients, the mean pupil size measured under an operating microscope was 3.2 mm preoperatively, 4.3 mm after viscoelastic and mechanical pupil dilation, and 4.1 mm at the end of a surgical procedure. Rupture of the zonular fibers occurred in six patients of group I and the intraocular lens was implanted in the sulcus. Small iris sphincter rupture and small hemorrhages occurred in four eyes during pupillary manipulation, but they were not evident at the end of the surgery. In group II patients, no intraoperative complications occurred. Signs of significant corneal edema and iritis were observed more frequently in group I eyes (26 eyes and 20 eyes, respectively) on the first postoperative day in comparison with group II eyes (ten eyes and six eyes, respectively). Intraocular pressure was <20 mmHg in all eyes of both groups. One month postoperatively, the pupil was round and reactive to light, the anterior chamber was quiet, and the cornea was clear in all eyes. The best-corrected visual acuity on Snellen chart was 20/40 (Monoyer's scale) or better in both groups. CONCLUSION: Phacoemulsification through a small pupil using minimal iris manipulation can be safe and exhibits the same results as those obtained with phacoemulsification through normal pupils. PMID- 27274214 TI - Does severity of dermatochalasis in aging affect corneal biomechanical properties? AB - PURPOSE: The aim of this study was to investigate the possibility of a relationship between corneal biomechanical properties and different grades of dermatochalasis. PATIENTS AND METHODS: Patients were assigned to four groups according to the severity of their dermatochalasis: normal (Group 1), mild (Group 2), moderate (Group 3), and severe (Group 4). An Ocular Response Analyzer device was used to measure corneal hysteresis (CH), corneal resistance factor (CRF), and corneal-compensated intraocular pressure (IOPcc). RESULTS: We found no significant differences in the mean values of the CH, CRF, and IOPcc of all groups (P=0.75, P=0.93, and P=0.11, respectively). However, CH and IOPcc were negatively correlated in Group 1, Group 2, and Group 3 patients (P=0.013, r= 0.49; P=0.015, r=-0.52; and P=0.011, r=-0.47, respectively), but this correlation was not apparent in the Group 4 patients (P=0.57, r=0.12). CRF and IOPcc were correlated, but only in Group 4 (P=0.001, r=0.66). CONCLUSION: Severe dermatochalasis was associated with altered corneal biomechanical properties. Some of the important visual consequences of dermatochalasis and related diseases (such as floppy eyelid syndrome) can be understood by considering corneal biomechanical alterations. PMID- 27274216 TI - A randomized clinical trial of neurally adjusted ventilatory assist versus conventional weaning mode in patients with COPD and prolonged mechanical ventilation. AB - BACKGROUND: Patient-ventilator asynchrony is a common problem in mechanically ventilated patients; the problem is especially obvious in COPD. Neutrally adjusted ventilatory assist (NAVA) can improve patient-ventilator asynchrony; however, the effect in COPD patients with prolonged mechanical ventilation is still unknown. The goals of this study are to evaluate the effect of NAVA and conventional weaning mode in patients with COPD during prolonged mechanical ventilation. METHODS: The study enrolled a total of 33 COPD patients with ventilator dependency for more than 21 days in the weaning center. A diaphragm electrical activity (Edi) catheter was inserted in patients within 24 hours after admission to the respiratory care center, and patients were randomly allocated to NAVA or conventional group. A spontaneous breathing trial was performed every 24 hours. The results correlated with the clinical parameters. RESULTS: There were significantly higher asynchrony incidence rates in the whole group after using Edi catheter (before vs post-Edi catheter insertion =60.6% vs 87.9%, P<0.001). Asynchrony index: before vs post-Edi catheter insertion =7.4%+/-8.5% vs 13.2%+/ 13.5%, P<0.01. Asynchrony incidence: NAVA vs conventional =0% vs 84.2%, P<0.001. Asynchrony index: NAVA vs conventional =0 vs 11.9+/-11.2 (breath %), P<0.001. The most common asynchrony events were ineffective trigger and delayed trigger. CONCLUSION: Compared to conventional mode, NAVA mode can significantly enhance respiratory monitoring and improve patient-ventilator interaction in COPD patients with prolonged mechanical ventilation in respiratory care center. PMID- 27274215 TI - Genes associated with Alzheimer's disease: an overview and current status. AB - Alzheimer's disease (AD) is a progressive, neurodegenerative disease and the most common form of dementia in elderly people. It is an emerging public health problem that poses a huge societal burden. Linkage analysis was the first milestone in unraveling the mutations in APP, PSEN1, and PSEN2 that cause early onset AD, followed by the discovery of apolipoprotein E-epsilon4 allele as the only one genetic risk factor for late-onset AD. Genome-wide association studies have revolutionized genetic research and have identified over 20 genetic loci associated with late-onset AD. Recently, next-generation sequencing technologies have enabled the identification of rare disease variants, including unmasking small mutations with intermediate risk of AD in PLD3, TREM2, UNC5C, AKAP9, and ADAM10. This review provides an overview of the genetic basis of AD and the relationship between these risk genes and the neuropathologic features of AD. An understanding of genetic mechanisms underlying AD pathogenesis and the potentially implicated pathways will lead to the development of novel treatment for this devastating disease. PMID- 27274218 TI - A randomized, parallel-group study to evaluate the efficacy of umeclidinium/vilanterol 62.5/25 MUg on health-related quality of life in patients with COPD. AB - BACKGROUND: The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with the long-acting beta2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health related quality of life and symptomatic outcomes in a similar population. METHODS: This was a 12-week multicenter, randomized, double-blind, parallel group, placebo-controlled study. Eligible patients were randomized 1:1 to receive once-daily UMEC/VI 62.5/25 MUg (via ELLIPTA((r)) dry powder inhaler) or PBO for 12 weeks. The primary endpoint was St George's Respiratory Questionnaire (SGRQ) total score at day 84. Secondary efficacy endpoints included rescue albuterol use (puffs/day) over weeks 1-12 and trough forced expiratory volume in 1 second on day 84. Adverse events were also assessed. RESULTS: A total of 496 patients were included in the intent-to-treat population in the UMEC/VI (n=248) and PBO (n=248) treatment groups. UMEC/VI 62.5/25 MUg provided a significant and clinically meaningful improvement in SGRQ total score at day 84 versus PBO (difference between treatments in SGRQ total score change from baseline: -4.03 [95% confidence interval {CI}: -6.28, -1.79]; P<0.001). UMEC/VI 62.5/25 MUg resulted in a statistically significant reduction in rescue albuterol use versus PBO (-0.7 puffs/day [95% CI: -1.1, -0.4]; P<0.001). UMEC/VI 62.5/25 MUg provided a significant and clinically meaningful improvement in trough forced expiratory volume in 1 second on day 84 versus PBO (122 mL [95% CI: 71, 172]; P<0.001). The incidence of adverse events was similar between treatments (32% and 30% of patients in the UMEC/VI 62.5/25 MUg and PBO groups, respectively). CONCLUSION: The results of this study demonstrate that treatment with UMEC/VI 62.5/25 MUg provides clinically important improvements in SGRQ and rescue medication use versus PBO in patients with moderate-to-very-severe COPD. PMID- 27274217 TI - Assessment of illness acceptance by patients with COPD and the prevalence of depression and anxiety in COPD. AB - BACKGROUND: COPD is a civilization disease. It affects up to 8%-10% of population >30 years of age. Coexistence of depression occurs in 20%-40% of patients with COPD. Depression and anxiety reduce compliance and worsen prognosis. OBJECTIVE: The aims of this study were to determine the degree of illness acceptance among patients with COPD, to examine the relation between disease acceptance and perceived anxiety and depression, and to verify which of the sociodemographic and clinical factors are associated with illness acceptance, anxiety, and depression. MATERIALS AND METHODS: The study included 102 patients with COPD (mean age 65.8 years), hospitalized due to exacerbations. Acceptance of Illness Scale and Hospital Anxiety and Depression Scale were used. For statistical analysis, Student's t-test and Pearson's r correlation coefficient were carried out. RESULTS: The overall illness acceptance level was moderate with a tendency toward lack of acceptance (mean 20.6, standard deviation [SD] 7.62). The overall scores were 10.2 (SD 3.32) for anxiety and 10.8 (SD 4.14) for depression, which indicate borderline or high intensity of these symptoms. Acceptance of illness was negatively correlated with the intensity of depression symptoms (r=-0.46, P<0.05). Intensity of depression was significantly associated with intensity of smoking, duration of the disease, severity of dyspnea, and living in a rural area. CONCLUSION: Early identification and assessment of depression and anxiety symptoms allow health care providers to offer patients at risk of depression a special medical supervision. Rapid start of antidepressant therapy may increase illness acceptance and improve prognosis among patients with COPD. PMID- 27274219 TI - Follow-up study on management of chronic obstructive pulmonary disease in Hunan Province, the People's Republic of China. AB - BACKGROUND: In 2009, our study showed an extreme imbalance and disparity in COPD related health resources allocation at three levels of public hospitals (PHs) in Hunan Province of the People's Republic of China, especially in second-level PHs. Moreover, most Chinese citizens accept their health care services in first- and second-level PHs for economic and geographical reasons, as well as because of the incomplete transfer system in the health care services. To improve diagnosis and treatment ability of pulmonologists in second-level PHs, an intervention that provided training combined with spirometry equipment was carried out in three PHs from six second-level PHs. The aim of this follow-up study was to evaluate the changes associated with COPD-related health resources allocation and the effect of the intervention 4 years later. METHODS: The data regarding the availability of spirometers, inhalation agents for COPD, and COPD-related health care education for local residents were collected from 57 PHs in 2009 and 48 PHs in 2013. Pulmonologists working in these PHs were asked to complete a questionnaire individually. Six second-level PHs (three in the intervention group and the other three in the control group [without training and spirometry equipment]) that further took part in the survey in 2009 were reevaluated to determine the doubtful diagnostic ratio and the confirmation ratio of COPD. The differences between 2009 and 2013 data was analyzed. RESULTS: A total of 762 questionnaires were completed. Compared with 2009, spirometer-equipped ratio raised from 40% to 69% in 2013 (P=0.03). The overall inhalation agent-equipped ratio increased from 58% in 2009 to 88% in 2013 (P=0.001). The total rate of health education raised from 35% in 2009 to 63% in 2013 (P=0.04). In total, 204 pulmonologists from six PHs (selected for study in 2009) completed the questionnaires in 2013. The median score of COPD knowledge questionnaire in the intervention group was higher than that of the control group (80 vs 50, respectively, P<0.01). Further, the clinical doubtful diagnostic ratio (15%) and the diagnosis ratio of COPD (3%) in the intervention group were higher than in the control group (4% and 1%, respectively, P<0.05) even after 4 years. CONCLUSION: COPD-related health resources allocation improved in the 4 years following intervention at three levels of PHs in the People's Republic of China. Short-term training combined with spirometry equipment had a sustained effect on improving the physicians' understanding and diagnosis ability of COPD. PMID- 27274220 TI - Comparison of pulmonary function in patients with COPD, asthma-COPD overlap syndrome, and asthma with airflow limitation. AB - BACKGROUND: This study was conducted in order to investigate the differences in the respiratory physiology of patients with chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome (ACOS), and asthma with airflow limitation (asthma FL(+)). METHODS: The medical records for a series of all stable patients with persistent airflow limitation due to COPD, ACOS, or asthma were retrospectively reviewed and divided into the COPD group (n=118), the ACOS group (n=32), and the asthma FL(+) group (n=27). All the patients underwent chest high resolution computed tomography (HRCT) and pulmonary function tests, including respiratory impedance. RESULTS: The low attenuation area score on chest HRCT was significantly higher in the COPD group than in the ACOS group (9.52+/-0.76 vs 5.09+/-1.16, P<0.01). The prevalence of bronchial wall thickening on chest HRCT was significantly higher in the asthma FL(+) group than in the COPD group (55.6% vs 25.0%, P<0.01). In pulmonary function, forced expiratory volume in 1 second (FEV1) and peak expiratory flow rate were significantly higher in the asthma FL(+) group than in the ACOS group (76.28%+/-2.54% predicted vs 63.43%+/-3.22% predicted, P<0.05 and 74.40%+/-3.16% predicted vs 61.08%+/-3.54% predicted, P<0.05, respectively). Although residual volume was significantly lower in the asthma FL(+) group than in the COPD group (112.05%+/-4.34% predicted vs 137.38%+/ 3.43% predicted, P<0.01) and the ACOS group (112.05%+/-4.34% predicted vs148.46%+/-6.25% predicted, P<0.01), there were no significant differences in functional residual capacity or total lung capacity. The increase in FEV1 in response to short-acting beta2-agonists was significantly greater in the ACOS group than in the COPD group (229+/-29 mL vs 72+/-10 mL, P<0.01) and the asthma FL(+) group (229+/-29 mL vs 153+/-21 mL, P<0.05). Regarding respiratory impedance, resistance at 5 Hz and resistance at 20 Hz, which are oscillatory parameters of respiratory resistance, were significantly higher in the asthma FL(+) group than in the COPD group at the whole-breath (4.29+/-0.30 cmH2O/L/s vs 3.41+/-0.14 cmH2O/L/s, P<0.01 and 3.50+/-0.24 cmH2O/L/s vs 2.68+/-0.10 cmH2O/L/s, P<0.01, respectively), expiratory, and inspiratory phases. CONCLUSION: Although persistent airflow limitation occurs in patients with COPD, ACOS, and asthma FL(+), they may have distinct characteristics of the respiratory physiology and different responsiveness to bronchodilators. PMID- 27274221 TI - Diagnosis of alpha-1 antitrypsin deficiency: a population-based study. AB - INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite initiatives developed to increase awareness. The objective was to describe the current situation of the diagnosis of AATD in primary care (PC) in Catalonia, Spain. METHODS: We performed a population-based study with data from the Information System for Development in Research in Primary Care, a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). We collected the number of alpha-1 antitrypsin (AAT) determinations performed in the PC in two periods (2007-2008 and 2010-2011) and described the characteristics of the individuals tested. RESULTS: A total of 12,409 AAT determinations were performed (5,559 in 2007-2008 and 6,850 in 2010 2011), with 10.7% of them in children. As a possible indication for AAT determination, 28.9% adults and 29.4% children had a previous diagnosis of a disease related to AATD; transaminase levels were above normal in 17.7% of children and 47.1% of adults. In total, 663 (5.3%) individuals had intermediate AATD (50-100 mg/dL), 24 (0.2%) individuals had a severe deficiency (<50 mg/dL), with a prevalence of 0.19 cases of severe deficiency per 100 determinations. Nine (41%) of the adults with severe deficiency had a previous diagnosis of COPD/emphysema, and four (16.7%) were diagnosed with COPD within 6 months. CONCLUSION: The number of AAT determinations in the PC is low in relation to the prevalence of COPD but increased slightly along the study period. The indication to perform the test is not always clear, and patients detected with deficiency are not always referred to a specialist. PMID- 27274222 TI - Extracellular cadmium in the bronchoalveolar space of long-term tobacco smokers with and without COPD and its association with inflammation. AB - Tobacco contains cadmium, and this metal has been attributed a causative role in pulmonary emphysema among smokers, although extracellular cadmium has not to date been quantified in the bronchoalveolar space of tobacco smokers with or without COPD. We determined whether cadmium is enhanced in the bronchoalveolar space of long-term tobacco smokers with or without COPD in vivo, its association with inflammation, and its effect on chemokine release in macrophage-like cells in vitro. Bronchoalveolar lavage (BAL), sputum, and blood samples were collected from current, long-term smokers with and without COPD and from healthy nonsmokers. Cadmium concentrations were determined in cell-free BAL fluid using inductively coupled plasma mass spectrometry. Blood monocyte-derived macrophages were exposed to cadmium chloride in vitro. Depending upon the type of sample, molecular markers of inflammation were quantified either as protein (enzyme linked immunosorbent assay) or as mRNA (real-time polymerase chain reaction). Cadmium concentrations were markedly increased in cell-free BAL fluid of smokers compared to that of nonsmokers (n=19-29; P<0.001), irrespective of COPD. In these smokers, the measured cadmium displayed positive correlations with macrophage TNF alpha mRNA in BAL, neutrophil and CD8(+) cell concentrations in blood, and finally with IL-6, IL-8, and MMP-9 protein in sputum (n=10-20; P<0.05). The cadmium chloride exposure caused a concentration-dependent increase in extracellular IL-8 protein in monocyte-derived macrophages in vitro. In conclusion, extracellular cadmium is enhanced in the bronchoalveolar space of long-term smokers and displays pro-inflammatory features. Its pathogenic role in tobacco-induced disease deserves further evaluation. PMID- 27274224 TI - Erratum: Triple therapy with salmeterol/fluticasone propionate 50/250 plus tiotropium bromide improve lung function versus individual treatments in moderate to-severe Japanese COPD patients: a randomized controlled trial - Evaluation of Airway sGaw after treatment with tripLE [Corrigendum]. AB - [This corrects the article on p. 2393 in vol. 10, PMID: 26604737.]. PMID- 27274223 TI - A comparison of synchronized intermittent mandatory ventilation and pressure regulated volume control ventilation in elderly patients with acute exacerbations of COPD and respiratory failure. AB - BACKGROUND: COPD is the third leading cause of death worldwide. Acute exacerbations of COPD may cause respiratory failure, requiring intensive care unit admission and mechanical ventilation. Intensive care unit patients with acute exacerbations of COPD requiring mechanical ventilation have higher mortality rates than other hospitalized patients. Although mechanical ventilation is the most effective intervention for these conditions, invasive ventilation techniques have yielded variable effects. OBJECTIVE: We evaluated pressure regulated volume control (PRVC) ventilation treatment efficacy and preventive effects on pulmonary barotrauma in elderly COPD patients with respiratory failure. PATIENTS AND METHODS: Thirty-nine intubated patients were divided into experimental and control groups and treated with the PRVC and synchronized intermittent mandatory ventilation - volume control methods, respectively. Vital signs, respiratory mechanics, and arterial blood gas analyses were monitored for 2-4 hours and 48 hours. RESULTS: Both groups showed rapidly improved pH, partial pressure of oxygen (PaO2), and PaO2 per fraction of inspired O2 levels and lower partial pressure of carbon dioxide (PaCO2) levels. The pH and PaCO2 levels at 2-4 hours were lower and higher, respectively, in the test group than those in the control group (P<0.05 for both); after 48 hours, blood gas analyses showed no statistical difference in any marker (P>0.05). Vital signs during 2-4 hours and 48 hours of treatment showed no statistical difference in either group (P>0.05). The level of peak inspiratory pressure in the experimental group after mechanical ventilation for 2-4 hours and 48 hours was significantly lower than that in the control group (P<0.05), while other variables were not significantly different between groups (P>0.05). CONCLUSION: Among elderly COPD patients with respiratory failure, application of PRVC resulted in rapid improvement in arterial blood gas analyses while maintaining a low peak inspiratory pressure. PRVC can reduce pulmonary barotrauma risk, making it a safer protective ventilation mode than synchronized intermittent mandatory ventilation - volume control. PMID- 27274225 TI - Effects of budesonide on toll-like receptor expression in alveolar macrophages from smokers with and without COPD. AB - INTRODUCTION: Alveolar macrophages (AMs) are equipped with innate immune receptors such as toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4). In primary bronchial epithelial cells, exposure of toll-like receptor (TLR) ligands or tumor necrosis factor-alpha (TNF-alpha) increased TLR2 mRNA expression and reduced interleukin-8 (IL-8) release when coincubated with glucocorticosteroids. The aim of this study was to compare TLR2 and TLR4 expression levels and the effect of a glucocorticosteroid after stimulation with TLR ligands on AMs from smokers with and without COPD compared with the healthy controls. SUBJECTS AND METHODS: Bronchoalveolar lavage was performed, and AMs were isolated from smokers with (n=10) and without COPD (n=11) and healthy controls (n=10) and stimulated ex vivo with peptidoglycan (PGN), lipopolysaccharide (LPS), or TNF-alpha +/- budesonide (Bud). Blocking antibodies to TLR2 or TLR4 were added before stimulation with LPS or PGN +/- Bud, respectively. The release of proinflammatory cytokine (TNF-alpha), chemoattractant (CXCL8), and TLR expression was analyzed by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. RESULTS: LPS, PGN, and TNF-alpha induced an increased release of IL-8 and TNF-alpha in the AMs in all the groups independent of smoking or disease. These responses were inhibited by a glucocorticosteroid (Bud) in all the three groups, except PGN-induced IL-8 secretion in smokers without COPD. Bud increased TLR2 expression in the healthy controls and smokers without COPD. Costimulation of TLR ligands and Bud significantly enhanced TLR2 mRNA expression in both groups of smokers compared with TLR ligands alone. In smokers, costimulation with PGN and Bud significantly increased TLR2 expression when compared with Bud alone. On stimulation with the TLR4 agonist, LPS downregulated TLR4 mRNA expression in all the three groups. CONCLUSION: The combination of glucocorticosteroids with TLR ligands can increase TLR2 expression, thereby improving host defense in smokers. Also this combination can decrease the secretion of proinflammatory cytokines and chemokines as an anti-inflammatory response. Our findings indicate that glucocorticosteroid therapy strengthens immune defense pathways, which may have implication during exacerbation caused by microorganisms. PMID- 27274226 TI - Investigating sensitivity, specificity, and area under the curve of the Clinical COPD Questionnaire, COPD Assessment Test, and Modified Medical Research Council scale according to GOLD using St George's Respiratory Questionnaire cutoff 25 (and 20) as reference. AB - BACKGROUND: In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ >=1, CAT >=10, and mMRC scale >=2 to indicate symptomatic patients. The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George's Respiratory Questionnaire (SGRQ) >=25, as suggested by GOLD, following sensitivity and specificity analysis. In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (>=25 and >=20). MATERIALS AND METHODS: Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care. Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires. RESULTS: Sensitivity, specificity, and AUC scores for cutoff point SGRQ >=25 were: study A, 0.99, 0.43, and 0.96 for CCQ >=1, 0.92, 0.48, and 0.89 for CAT >=10, and 0.68, 0.91, and 0.91 for mMRC >=2; study B, 0.87, 0.77, and 0.9 for CCQ >=1, 0.76, 0.73, and 0.82 for CAT >=10, and 0.21, 1, and 0.81 for mMRC >=2. Sensitivity, specificity, and AUC scores for cutoff point SGRQ >=20 were: study A, 0.99, 0.73, and 0.99 for CCQ >=1, 0.91, 0.73, and 0.94 for CAT >=10, and 0.66, 0.95, and 0.94 for mMRC >=2; study B, 0.8, 0.89, and 0.89 for CCQ >=1, 0.69, 0.78, and 0.8 for CAT >=10, and 0.18, 1, and 0.81 for mMRC >=2. CONCLUSION: Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (>=25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels. The correspondence with the mMRC scale seemed satisfactory, though not optimal. The SGRQ threshold of >=20 corresponded slightly better than SGRQ >=25, recently suggested by GOLD 2015, with the established cutoff points for the CCQ, CAT, and mMRC scale. PMID- 27274227 TI - Hyperlipidemia in COPD is associated with decreased incidence of pneumonia and mortality: a nationwide health insurance data-based retrospective cohort study. AB - PURPOSE: COPD is often associated with various comorbidities that may influence its outcomes. Pneumonia, cardiovascular disease (CVD), and cancer are the major causes of death in COPD patients. The objective of this study is to investigate the influence of comorbidities on COPD by using the Taiwan National Health Insurance database. PATIENTS AND METHODS: We retrospectively analyzed the database in 2006 of one million sampling cohort. Newly diagnosed patients with COPD with a controlled cohort that was matched by age, sex, and Charlson comorbidity index (CCI) were included for analysis. RESULTS: In total, 1,491 patients with COPD were included for analysis (61.8% male). Patients with COPD had higher incidences of pneumonia (25.7% vs 10.4%; P<0.0001), CVD (15.1% vs 10.5%; P<0.0001), and mortality rate (26.6% vs 15.8%; P<0.001) compared with the control group in the 4-year follow-up. In patients with COPD, CCI >=3 have a higher incidence of pneumonia (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.23-2.09; P<0.0001), CVD (HR 1.73; 95% CI 1.24-2.41; P=0.001), and mortality (HR 1.12; 95% CI 1.12-1.83; P=0.004). Among the major comorbidities of COPD, hyperlipidemia was associated with decreased incidence of pneumonia (HR 0.68; 95% CI 0.5-0.93; P=0.016) and mortality (HR 0.64; 95% CI 0.46-0.90; P=0.009), but was not associated with increased risk of CVD (HR 1.10; 95% CI 0.78 1.55; P=0.588). CONCLUSION: Our results demonstrate that COPD is associated with increased incidence of pneumonia, CVD, and mortality. In patients with COPD, higher CCI is associated with increased incidence of pneumonia, CVD, and mortality. However, COPD with hyperlipidemia is associated with decreased incidence of pneumonia and mortality. PMID- 27274228 TI - Capturing and concentrating adenovirus using magnetic anionic nanobeads. AB - We recently demonstrated how various enveloped viruses can be efficiently concentrated using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate). However, the exact mechanism of interaction between the virus particles and anionic beads remains unclear. To further investigate whether these magnetic anionic beads specifically bind to the viral envelope, we examined their potential interaction with a nonenveloped virus (adenovirus). The beads were incubated with either adenovirus-infected cell culture medium or nasal aspirates from adenovirus-infected individuals and then separated from the supernatant by applying a magnetic field. After thoroughly washing the beads, adsorption of adenovirus was confirmed by a variety of techniques, including immunochromatography, polymerase chain reaction, Western blotting, and cell culture infection assays. These detection methods positively identified the hexon and penton capsid proteins of adenovirus along with the viral genome on the magnetic beads. Furthermore, various types of adenovirus including Types 5, 6, 11, 19, and 41 were captured using the magnetic bead procedure. Our bead capture method was also found to increase the sensitivity of viral detection. Adenovirus below the detectable limit for immunochromatography was efficiently concentrated using the magnetic bead procedure, allowing the virus to be successfully detected using this methodology. Moreover, these findings clearly demonstrate that a viral envelope is not required for binding to the anionic magnetic beads. Taken together, our results show that this capture procedure increases the sensitivity of detection of adenovirus and would, therefore, be a valuable tool for analyzing both clinical and experimental samples. PMID- 27274229 TI - Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles. AB - Magnetic hyperthermia - a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs) are made to resonantly respond to an alternating magnetic field (AMF) and thereby produce heat - is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs) can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks) post integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran((r)) was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 uL in volume and then entered a rapid growth phase over the third week to reach ~300 uL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI) data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4 degrees C were observed during the first application, after which MRI indicated a loss of negative contrast, suggesting that the MSCs had died and been cleared from the tumor. This post-AMF removal of cells was confirmed by histological examination and also by a reduced level of subsequent magnetic heating effect. Despite this evidence for an AMF-elicited response in the SPION-loaded MSCs, and in contrast to previous reports on tumor remission in immunocompetent mouse models, in this case, no significant differences were measured regarding the overall tumor size or growth characteristics. We discuss the implications of these results on the clinical delivery of hyperthermia therapy to tumors and on the possibility that a preferred therapeutic route may involve AMF as an adjuvant to an autologous immune response. PMID- 27274230 TI - Erratum: Enhanced detection of single-cell-secreted proteins using a fluorescent immunoassay on the protein-G-terminated glass substrate [Corrigendum]. AB - [This corrects the article on p. 7197 in vol. 10, PMID: 26648723.]. PMID- 27274232 TI - Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel. AB - In this study, the ability of nanocarriers containing protein transduction domains (PTDs) of various classes to improve cutaneous paclitaxel delivery and efficacy in skin tumor models was evaluated. Microemulsions (MEs) were prepared by mixing a surfactant blend (polyoxyethylene 10 oleoyl ether, ethanol and propylene glycol), monocaprylin, and water. The PTD transportan (ME-T), penetratin (ME-P), or TAT (ME-TAT) was added at a concentration of 1 mM to the plain ME. All MEs displayed nanometric size (32.3-40.7 nm) and slight positive zeta potential (+4.1 mV to +6.8 mV). Skin penetration of paclitaxel from the MEs was assessed for 1-12 hours using porcine skin and Franz diffusion cells. Among the PTD-containing formulations, paclitaxel skin (stratum corneum + epidermis and dermis) penetration at 12 hours was maximized with ME-T, whereas ME-TAT provided the lowest penetration (1.6-fold less). This is consistent with the stronger ability of ME-T to increase transepidermal water loss (2.4-fold compared to water) and tissue permeability. The influence of PTD addition on the ME irritation potential was assessed by measuring interleukin-1alpha expression and viability of bioengineered skin equivalents. A 1.5- to 1.8-fold increase in interleukin-1alpha expression was induced by ME-T compared to the other formulations, but this effect was less pronounced (5.8-fold) than that mediated by the moderate irritant Triton. Because ME-T maximized paclitaxel cutaneous localization while being safer than Triton, its efficacy was assessed against basal cell carcinoma cells and a bioengineered three-dimensional melanoma model. Paclitaxel-containing ME-T reduced cells and tissue viability by twofold compared to drug solutions, suggesting the potential clinical usefulness of the formulation for the treatment of cutaneous tumors. PMID- 27274233 TI - Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy. AB - In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe3O4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity (r 2) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity (r 1) (r 2/r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T2-weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy. PMID- 27274234 TI - Carbon nanospheres mediated delivery of nuclear matrix protein SMAR1 to direct experimental autoimmune encephalomyelitis in mice. AB - Owing to the suppression of immune responses and associated side effects, steroid based treatments for inflammatory encephalitis disease can be detrimental. Here, we demonstrate a novel carbon nanosphere (CNP) based treatment regime for encephalomyelitis in mice by exploiting the functional property of the nuclear matrix binding protein SMAR1. A truncated part of SMAR1 ie, the DNA binding domain was conjugated with hydrothermally synthesized CNPs. When administered intravenously, the conjugate suppressed experimental animal encephalomyelitis in T cell specific conditional SMAR1 knockout mice (SMAR(-/-)). Further, CNP-SMAR1 conjugate delayed the onset of the disease and reduced the demyelination significantly. There was a significant decrease in the production of IL-17 after re-stimulation with MOG. Altogether, our findings suggest a potential carbon nanomaterial based therapeutic intervention to combat Th17 mediated autoimmune diseases including experimental autoimmune encephalomyelitis. PMID- 27274235 TI - Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects. AB - The mineralization of collagen scaffolds can improve their mechanical properties and biocompatibility, thereby providing an appropriate microenvironment for bone regeneration. The primary purpose of the present study is to fabricate a synergistically intra- and extrafibrillar mineralized collagen scaffold, which has many advantages in terms of biocompatibility, biomechanical properties, and further osteogenic potential. In this study, mineralized collagen scaffolds were fabricated using a traditional mineralization method (ie, immersed in simulated body fluid) as a control group and using a biomimetic method based on the polymer induced liquid precursor process as an experimental group. In the polymer-induced liquid precursor process, a negatively charged polymer, carboxymethyl chitosan (CMC), was used to stabilize amorphous calcium phosphate (ACP) to form nanocomplexes of CMC/ACP. Collagen scaffolds mineralized based on the polymer induced liquid precursor process were in gel form such that nanocomplexes of CMC/ACP can easily be drawn into the interstices of the collagen fibrils. Scanning electron microscopy and transmission electron microscopy were used to examine the porous micromorphology and synergistic mineralization pattern of the collagen scaffolds. Compared with simulated body fluid, nanocomplexes of CMC/ACP significantly increased the modulus of the collagen scaffolds. The results of in vitro experiments showed that the cell count and differentiated degrees in the experimental group were higher than those in the control group. Histological staining and micro-computed tomography showed that the amount of new bone regenerated in the experimental group was larger than that in the control group. The biomimetic mineralization will assist us in fabricating a novel collagen scaffold for clinical applications. PMID- 27274231 TI - Current application of phytocompound-based nanocosmeceuticals for beauty and skin therapy. AB - Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care. Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy. PMID- 27274236 TI - Long-term effect of ropivacaine nanoparticles for sciatic nerve block on postoperative pain in rats. AB - PURPOSE: The analgesic effect of ropivacaine (Rop) for nerve block lasts only ~3 6 hours for single use. The aim of this study was to develop long-acting regional anesthetic Rop nanoparticles and investigate the effects of sciatic nerve block on postoperative pain in rats. MATERIALS AND METHODS: Rop nanoparticles were developed using polyethylene glycol-co-polylactic acid (PELA). One hundred and twenty adult male Wistar rats were randomly divided into four groups (n=30, each): Con (control group; 0.9% saline, 200 uL), PELA (PELA group; 10 mg), Rop (Rop group; 0.5%, 200 uL), and Rop-PELA (Rop-PELA group; 10%, 10 mg). Another 12 rats were used for the detection of Rop concentration in plasma. The mechanical withdrawal threshold and thermal withdrawal latency were measured at 2 hours, 4 hours, 8 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. The expression of c-FOS was determined by immunohistochemistry at 2 hours, 8 hours, 48 hours, and 7 days. Nerve and organ toxicities were also evaluated at 7 days. RESULTS: The duration of Rop absorption in the plasma of the Rop-PELA group was longer (>8 hours) than that of the Rop group (4 hours). Mechanical withdrawal threshold and thermal withdrawal latency in the Rop-PELA group were higher than that in other groups (4 hours-3 days). c-FOS expression in the Rop-PELA group was lower than that in the control group at 2 hours, 8 hours, and 48 hours and lower than that in the Rop group at 8 hours and 48 hours after paw incision. Slight foreign body reactions were observed surrounding the sciatic nerve at 7 days. No obvious pathophysiological change was found in the major organs after Rop-PELA administration at 7 days. CONCLUSION: Rop-PELA provides an effective analgesia for nerve block over 3 days after single administration, and the analgesic mechanism might be mediated by the regulation of spinal c-FOS expression. However, its potential long-term tissue toxicity needs to be further investigated. PMID- 27274237 TI - Improving the osteogenesis of human bone marrow mesenchymal stem cell sheets by microRNA-21-loaded chitosan/hyaluronic acid nanoparticles via reverse transfection. AB - Cell sheet engineering has emerged as a novel approach to effectively deliver seeding cells for tissue regeneration, and developing human bone marrow mesenchymal stem cell (hBMMSC) sheets with high osteogenic ability is a constant requirement from clinics for faster and higher-quality bone formation. In this work, we fabricated biocompatible and safe chitosan (CS)/hyaluronic acid (HA) nanoparticles (NPs) to deliver microRNA-21 (miR-21), which has been proved to accelerate osteogenesis in hBMMSCs; then, the CS/HA/miR-21 NPs were cross-linked onto the surfaces of culture plates with 0.2% gel solution to fabricate miR-21 functionalized culture plates for reverse transfection. hBMMSC sheets were induced continuously for 14 days using a vitamin C-rich method on the miR-21 functionalized culture plates. For the characterization of CS/HA/miR-21 NPs, the particle size, zeta potential, surface morphology, and gel retardation were sequentially investigated. Then, the biological effects of hBMMSC sheets on the miR-21-functionalized culture plates were evaluated. The assay results demonstrated that the hBMMSC sheets could be successfully induced via the novel reverse transfection approach, and miR-21 delivery significantly enhanced the in vitro osteogenic differentiation of hBMMSC sheets in terms of upregulating calcification-related gene expression and enhancing alkaline phosphatase production, collagen secretion, and mineralized nodule formation. The enhanced osteogenic activity of hBMMSC sheets might promisingly lead to more rapid and more robust bone regeneration for clinical use. PMID- 27274238 TI - Current status and perspectives in atomic force microscopy-based identification of cellular transformation. AB - Understanding the complex interplay between cells and their biomechanics and how the interplay is influenced by the extracellular microenvironment, as well as how the transforming potential of a tissue from a benign to a cancerous one is related to the dynamics of both the cell and its surroundings, holds promise for the development of targeted translational therapies. This review provides a comprehensive overview of atomic force microscopy-based technology and its applications for identification of cellular progression to a cancerous phenotype. The review also offers insights into the advancements that are required for the next user-controlled tool to allow for the identification of early cell transformation and thus potentially lead to improved therapeutic outcomes. PMID- 27274239 TI - Aptamer-polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing. AB - Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs), which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti epithelial cell adhesion molecule coated aptamer-poly (N-isopropylacrylamide) functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32 degrees C and 4 degrees C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush), which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate-tumor chemosensitivity assay, and the results suggested that our method can determine which agent and what concentration have the best chemosensitivity for the culturing recovered CTCs. So, the novel method capable of a highly effective capture and recovery of high viability CTCs will pave the way for chemosensitivity testing. PMID- 27274240 TI - Prevention of vaginal and rectal herpes simplex virus type 2 transmission in mice: mechanism of antiviral action. AB - Topical microbicides to stop sexually transmitted diseases, such as herpes simplex virus type 2 (HSV-2), are urgently needed. The emerging field of nanotechnology offers novel suitable tools for addressing this challenge. Our objective was to study, in vitro and in vivo, antiherpetic effect and antiviral mechanisms of several polyanionic carbosilane dendrimers with anti-HIV-1 activity to establish new potential microbicide candidates against sexually transmitted diseases. Plaque reduction assay on Vero cells proved that G2-S16, G1-S4, and G3 S16 are the dendrimers with the highest inhibitory response against HSV-2 infection. We also demonstrated that our dendrimers inhibit viral infection at the first steps of HSV-2 lifecycle: binding/entry-mediated events. G1-S4 and G3 S16 bind directly on the HSV-2, inactivating it, whereas G2-S16 adheres to host cell-surface proteins. Molecular modeling showed that G1-S4 binds better at binding sites on gB surface than G2-S16. Significantly better binding properties of G1-S4 than G2-S16 were found in an important position for affecting transition of gB trimer from G1-S4 prefusion to final postfusion state and in several positions where G1-S4 could interfere with gB/gH-gL interaction. We demonstrated that these polyanionic carbosilan dendrimers have a synergistic activity with acyclovir and tenofovir against HSV-2, in vitro. Topical vaginal or rectal administration of G1-S4 or G2-S16 prevents HSV-2 transmission in BALB/c mice in values close to 100%. This research represents the first demonstration that transmission of HSV-2 can be blocked by vaginal/rectal application of G1-S4 or G2 S16, providing a step forward to prevent HSV-2 transmission in humans. PMID- 27274241 TI - Manipulating the NF-kappaB pathway in macrophages using mannosylated, siRNA delivering nanoparticles can induce immunostimulatory and tumor cytotoxic functions. AB - Tumor-associated macrophages (TAMs) are critically important in the context of solid tumor progression. Counterintuitively, these host immune cells can often support tumor cells along the path from primary tumor to metastatic colonization and growth. Thus, the ability to transform protumor TAMs into antitumor, immune reactive macrophages would have significant therapeutic potential. However, in order to achieve these effects, two major hurdles would need to be overcome: development of a methodology to specifically target macrophages and increased knowledge of the optimal targets for cell-signaling modulation. This study addresses both of these obstacles and furthers the development of a therapeutic agent based on this strategy. Using ex vivo macrophages in culture, the efficacy of mannosylated nanoparticles to deliver small interfering RNA specifically to TAMs and modify signaling pathways is characterized. Then, selective small interfering RNA delivery is tested for the ability to inhibit gene targets within the canonical or alternative nuclear factor-kappaB pathways and result in antitumor phenotypes. Results confirm that the mannosylated nanoparticle approach can be used to modulate signaling within macrophages. We also identify appropriate gene targets in critical regulatory pathways. These findings represent an important advance toward the development of a novel cancer therapy that would minimize side effects because of the targeted nature of the intervention and that has rapid translational potential. PMID- 27274243 TI - In vitro and in vivo targeting imaging of pancreatic cancer using a Fe3O4@SiO2 nanoprobe modified with anti-mesothelin antibody. AB - Pancreatic cancer is a highly malignant disease with a 5-year survival rate <5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533+/-31.56 before injecting A-MFS and 691.133+/-56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533+/-42.6. The signal value decreased by -61.233+/-33.9 and -58.7+/-19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P<0.05). The results demonstrated the high stability and nontoxicity of A-MFS, which effectively targeted pancreatic cancer in vitro and in vivo. A-MFS is a promising agent for diagnosis of pancreatic cancer. PMID- 27274242 TI - Vesicular (liposomal and nanoparticulated) delivery of curcumin: a comparative study on carbon tetrachloride-mediated oxidative hepatocellular damage in rat model. AB - The liver plays a vital role in biotransforming and extricating xenobiotics and is thus prone to their toxicities. Short-term administration of carbon tetrachloride (CCl4) causes hepatic inflammation by enhancing cellular reactive oxygen species (ROS) level, promoting mitochondrial dysfunction, and inducing cellular apoptosis. Curcumin is well accepted for its antioxidative and anti inflammatory properties and can be considered as an effective therapeutic agent against hepatotoxicity. However, its therapeutic efficacy is compromised due to its insolubility in water. Vesicular delivery of curcumin can address this limitation and thereby enhance its effectiveness. In this study, it was observed that both liposomal and nanoparticulated formulations of curcumin could increase its efficacy significantly against hepatotoxicity by preventing cellular oxidative stress. However, the best protection could be obtained through the polymeric nanoparticle-mediated delivery of curcumin. Mitochondria have a pivotal role in ROS homeostasis and cell survivability. Along with the maintenance of cellular ROS levels, nanoparticulated curcumin also significantly (P<0.0001) increased cellular antioxidant enzymes, averted excessive mitochondrial destruction, and prevented total liver damage in CCl4-treated rats. The therapy not only prevented cells from oxidative damage but also arrested the intrinsic apoptotic pathway. In addition, it also decreased the fatty changes in hepatocytes, centrizonal necrosis, and portal inflammation evident from the histopathological analysis. To conclude, curcumin-loaded polymeric nanoparticles are more effective in comparison to liposomal curcumin in preventing CCl4-induced oxidative stress-mediated hepatocellular damage and thereby can be considered as an effective therapeutic strategy. PMID- 27274244 TI - The relevancy of controlled nanocrystallization on rifampicin characteristics and cytotoxicity. AB - PURPOSE: This article investigated the influence of novel rifampicin nanosuspension (RIF NS) for enhancing drug delivery properties. METHODS: RIF NS was fabricated using the antisolvent precipitation technique. The impact of solvent type and flow rate, stabilizer type and concentration, and stirring time and apparatus together with the solvent-antisolvent volume ratio on its controlled nanocrystallization has been evaluated. NSs were characterized by transmission electron microscopy, particle size and zeta potential analysis, solubility, and dissolution profiles. The compatibility between RIF and the stabilizer was investigated via Fourier transform infrared spectroscopy and the differential scanning calorimetry techniques. The shelf-life stability of the RIF NS was assessed within a period of 3 months at different storage temperatures. Cell cytotoxicity was evaluated using 3(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay on lung epithelial cells. RESULTS: Polyvinyl alcohol at 0.4% w/v, 1:15 methanol to deionized water volume ratio and 30-minutes sonication were the optimal parameters for RIF NS preparation. Nanocrystals were obtained with a nanometeric particle size (101 nm) and a negative zeta potential (-26 mV). NS exhibited a 50-fold enhancement in RIF solubility and 97% of RIF was dissolved after 10 minutes. The RIF NS was stable at 4+/-0.5 degrees C with no significant change in particle size or zeta potential. The MTT cytotoxicity assay of RIF NS demonstrated a good safety profile and reduction in cell cytotoxicity with half maximal inhibitory concentration values of 0.5 and 0.8 mg/mL for free RIF and RIF NS, respectively. CONCLUSION: A novel RIF NS could be followed as an approach for enhancing RIF physicochemical characteristics with a prominence of a safer and better drug delivery. PMID- 27274245 TI - In vivo evaluation of the anti-infection potential of gentamicin-loaded nanotubes on titania implants. AB - Titanium-based implants have been widely used in orthopedic surgery; however, failures still occur. Our in vitro study has demonstrated that gentamicin-loaded, 80 nm-diameter nanotubes possessed both antibacterial and osteogenic activities. Thus, the aim of this study was to further investigate the in vivo anti-infection effect of the titanium implants with gentamicin-loaded nanotubes. Thirty-six male Sprague Dawley rats were used to establish an implant-associated infection model. A volume of 50 MUL Staphylococcus aureus suspension (1*10(5) CFU/mL) was injected into the medullary cavity of the left femur, and then the titanium rods without modification (Ti), titanium nanotubes without drug loading (NT), and gentamicin loaded titanium nanotubes (NT-G) were inserted with phosphate-buffered saline inoculated Ti rods as a blank control. X-ray images were obtained 1 day, 21 days, and 42 days after surgery; micro-computed tomography, microbiological, and histopathological analyses were used to evaluate the infections at the time of sacrifice. Radiographic signs of bone infection, including osteolysis, periosteal reaction, osteosclerosis, and damaged articular surfaces, were demonstrated in the infected Ti group and were slightly alleviated in the NT group but not observed in the NT-G group. Meanwhile, the radiographic and gross bone pathological scores of the NT-G group were significantly lower than those of the infected Ti group (P<0.01). Explant cultures revealed significantly less bacterial growth in the NT-G group than in the Ti and NT groups (P<0.01), and the NT group showed decreased live bacterial growth compared with the Ti group (P<0.01). Confocal laser scanning microscopy, scanning electron microscopy, and histopathological observations further confirmed decreased bacterial burden in the NT-G group compared with the Ti and NT groups. We concluded that the NT-G coatings can significantly prevent the development of implant-associated infections in a rat model; therefore, they may provide an effective drug-loading strategy to combat implant-associated infections in clinic. PMID- 27274246 TI - The prevalence and risk factors of stroke in patients with chronic schizophrenia. AB - OBJECTIVE: To investigate the stroke risk and risk factors in patients with chronic schizophrenia. PATIENTS AND METHODS: This study was a large-sample, cross sectional survey. A total of 363 patients with chronic schizophrenia were selected from the Changping Traditional Chinese Medicine Hospital, Beijing, in August 2014. The patients were divided into either stroke group or control group based on the presence of stroke. Clinical evaluation included positive and negative syndrome scale assessment and a detailed questionnaire to collect the general information and disease-related conditions. RESULTS: The prevalence of stroke was 16.5% (60 cases). Stroke and control groups showed a significant difference in age, sex, smoking, combined medication, doses, negative factor score in positive and negative syndrome scale, body mass index, waist circumference, and systolic blood pressure. Multivariate analysis showed that a number of factors are significantly related to stroke, including age, sex, smoking, combined medication, doses, body mass index, and systolic blood pressure. CONCLUSION: The prevalence of stroke is relatively higher in Chinese patients with chronic schizophrenia. Chronic schizophrenia patients are more likely to suffer from stroke; meanwhile, a number of risk factors were identified, including old age, female sex, smoking history, combined medication with a variety of drugs, high doses, obesity, and high blood pressure. PMID- 27274247 TI - Absence epilepsy and the CHD2 gene: an adolescent male with moderate intellectual disability, short-lasting psychoses, and an interstitial deletion in 15q26.1 q26.2. AB - Deletions of the 15q26 region encompassing the chromodomain helicase DNA binding domain 2 (CHD2) gene have been associated with intellectual disability, behavioral problems, and several types of epilepsy. Including the cases mentioned in ECARUCA (European cytogeneticists association register of unbalanced chromosome aberrations) and DECIPHER (database of genomic variation and phenotype in humans using ensembl resources), so far, a total of 13 intellectually disabled patients with a genetically proven deletion of the CHD2 gene are described, of whom eleven had a history of severe forms of epilepsy starting from a young age. In this article, a moderately intellectually disabled 15-year-old male with a 15q26.1-q26.2 interstitial deletion is reported, who was referred for analysis of two recent short-lasting psychotic episodes that were nonresponsive to antipsychotic treatment and recurrent disinhibited behaviors since early infancy. Careful interdisciplinary assessment revealed that the psychotic phenomena originated from a previously unrecognized absence epilepsy. Treatment with valproic acid was started which resulted in full remission of psychotic symptoms, and consequently, substantial improvement of behavior. It was concluded that in case of (rare) developmental disorders with genetically proven etiology, a detailed inventory of anamnestic data and description of symptomatology over time may elucidate epilepsy-related psychopathology for which a specific treatment regimen is needed. PMID- 27274248 TI - The impact of synapsin III gene on the neurometabolite level alterations after single-dose methylphenidate in attention-deficit hyperactivity disorder patients. AB - OBJECTIVE: To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS) in patients with attention-deficit hyperactivity disorder (ADHD). METHODS: Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel (1)H MRS when medication naive and 30 minutes after oral administration of 10 mg methylphenidate (Mph). Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA), choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses. RESULTS: After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020) and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014). Both rs133945G>A and rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with two-way repeated measure of analysis of variance. Post hoc comparisons revealed a significant difference between CG and GG genotypes of rs133946C>G polymorphisms after Bonferroni adjustment (P=0.016). CONCLUSION: Synapsin III gene polymorphisms may be affecting the changes in neurometabolite levels in response to Mph in adult ADHD patients. Future studies are needed to confirm our findings. PMID- 27274249 TI - A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression. AB - BACKGROUND: Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD). Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population. METHODS: Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups. RESULTS: The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation. CONCLUSION: Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder. Among them, comorbidity of anxiety disorders was significantly related to the efficacy for TRD including only major depressive disorder. Additional studies are needed to examine the association between the efficacy of aripiprazole augmentation and bipolarity, and these findings should be validated further in a prospective study. PMID- 27274250 TI - Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory. AB - It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD) patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients' quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed. PMID- 27274251 TI - Measuring negative symptoms in patients with schizophrenia: reliability and validity of the Korean version of the Motivation and Pleasure Scale-Self-Report. AB - BACKGROUND: The Clinical Assessment Interview for Negative Symptoms (CAINS) is one of the validated interview measures of negative symptoms in psychotic disorders. The Motivation and Pleasure Scale-Self-Report (MPSR) is a self-report measure that assesses the motivation and pleasure domains of negative symptoms based on the CAINS. This study evaluated the reliability and validity of a Korean version of the MPSR. METHODS: A total of 139 patients with schizophrenia completed the MPSR, CAINS, Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scales, Calgary Depression Scale for Schizophrenia, and other measures of trait and cognitive function. RESULTS: The 15-item MPSR showed good internal consistency. In addition, it also had a good convergent validity with the Motivation and Pleasure subscale of the CAINS and the anhedonia/avolition subscale of the SANS. The scale was not associated with psychotic symptoms, agitation/mania, and depression/anxiety, and it showed good discriminant validity. MPSR scores were significantly correlated with Behavioral Activation System total score for trait measure. CONCLUSION: The Korean version of the MPSR is a notable self-report method for examining the severity of negative symptoms in schizophrenia. PMID- 27274252 TI - Clinical usefulness of hemoencephalography beyond the neurofeedback. AB - AIM: Hemoencephalography (HEG) is an emerging procedure for clinical application in attention-deficit hyperactivity disorder and other disorders, regardless of age. It is available to any research group for its relative simplicity and low cost and is a useful tool for assessing prefrontal-dependent functions. Older teenagers pose peculiarities in the prefrontal maturation, and we aim to establish HEG patterns that might have clinical applicability. METHODS: The HEG patterns of 70 university students (56 women and 14 men, 21-48 years old, mean 31.84, SD 10.65, standard error of mean 0.31) were compared with those of 59 adolescents - 13-14-year-old secondary education students, 28 females and 31 males. The HEG patterns were obtained in response to the observation of shocking, unpleasant, and pleasant pictures. We use one-way and two-way analysis of variance to disentangle the differences between groups. All effects were analyzed with F-tests. RESULTS: In all cases, university students and adolescents showed a decrease in prefrontal activity, indicative of differences in the emotional inner networks between groups, which are responsible for security-insecurity processing. Compared with university students, adolescents showed statistically significant differences in decreased activity in very unpleasant (shocking) tests that demand increased security-insecurity processing. Adolescents showed lower decrease. In addition, adolescents, compared with university subjects, did not show statistically significantly decreased HEG activity compared with the baseline in very unpleasant tests. CONCLUSION: Teens showed distinguishable patterns of HEG, which were consistent with the cognitive emotional dysregulation in cognition and emotion interaction, that is, exterior network versus internal network interactions. Disability in regulation (modulation) of emotional response to negative emotional stimuli (fear of insecurity) in adolescence is an indicator of possible future clinical and psychiatric disorders such as depression and anxiety with high incidence of onset at this critical age and frequent comorbidity in attention-deficit hyperactivity disorder. HEG pattern might be a useful marker to define maturation and future possible mental dysfunctions. PMID- 27274253 TI - The role of psychiatrists in diagnosing conversion disorder: a mixed-methods analysis. AB - OBJECTIVE: Since DSM-5 removed the requirement for a psychosocial formulation, neurologists have been able to make the diagnosis of conversion disorder without psychiatric input. We sought to examine whether neurologists and specialist psychiatrists concurred with this approach. DESIGN: We used mixed methods, first surveying all the neurologists in the UK and then interviewing the neuropsychiatrists in a large UK region on the role of psychiatrists in diagnosing conversion disorder. RESULTS: Of the surveyed neurologists, 76% did not think that psychiatrists were essential for the diagnosis and 71% thought that psychiatrists did not even consider conversion disorder when referred a case. The neuropsychiatrists who were interviewed held complex models of conversion disorder. They believed all cases could be explained psychosocially in theory, but the nature of the diagnostic encounter often prevented it in practice; all felt that psychosocial formulation could be very helpful and some felt that it was essential to diagnosis. CONCLUSION: Although neurologists do not think psychiatrists are required for diagnosing conversion disorder, specialist psychiatrists disagree, at least in some cases. PMID- 27274254 TI - Efficacy and motor complications of original and generic levodopa in Parkinson's disease treatment. AB - BACKGROUND: In general, a generic drug is considered interchangeable with the original formulated drug. In Parkinson's disease (PD), generic drug use remains debated. This study was aimed to investigate whether the generic drug was as effective as the original in improving the symptoms of PD and the prevalence of motor complications. METHODS: This study was a multicenter cohort study of patients with PD enrolled from three northeast hospitals in Thailand between February 2013 and February 2014. The patients were categorized into original and generic levodopa groups. The clinical characteristics, efficacy, and motor complications were compared between the groups. RESULTS: There were 400 eligible patients. Of these, 327 patients (81.75%) met the study criteria and were classified as the original levodopa group (200 patients, 61.16%) and the generic levodopa group (127 patients, 38.84%). The average age of all patients with PD was 65 years. The duration of PD and the modified Hoehn-Yahr stages were not different between the groups. The total doses of original and generic levodopa equivalent doses were significantly different (199.97+/-127.08 versus 305.58+/ 138.27 mg; P-value <0.001) and the actual doses were 198.10+/-117.92 versus 308.85+/-139.40 mg (P-value <0.001). Approximately 80% of patients with PD in both groups had good responses (P-value >0.999), but the development of motor complications was significantly greater in the original than in the generic group. CONCLUSION: Generic levodopa was effective in improving the symptoms of PD. The prevalence of motor complications in the original compound group, at a lower dose of levodopa equivalent, was higher than in the generic group. PMID- 27274255 TI - A review of executive function deficits in autism spectrum disorder and attention deficit/hyperactivity disorder. AB - Executive dysfunction has been shown to be a promising endophenotype in neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). This article reviewed 26 studies that examined executive function comparing ASD and/or ADHD children. In light of findings from this review, the ASD + ADHD group appears to share impairment in both flexibility and planning with the ASD group, while it shares the response inhibition deficit with the ADHD group. Conversely, deficit in attention, working memory, preparatory processes, fluency, and concept formation does not appear to be distinctive in discriminating from ASD, ADHD, or ASD + ADHD group. On the basis of neurocognitive endophenotype, the common co-occurrence of executive function deficits seems to reflect an additive comorbidity, rather than a separate condition with distinct impairments. PMID- 27274256 TI - Clinical features, comorbidity, and cognitive impairment in elderly bipolar patients. AB - INTRODUCTION: Data specific to late-life bipolar disorder (BD) are limited. Current research is sparse and present guidelines are not adapted to this group of patients. OBJECTIVES: We present a literature review on clinical characteristics, comorbidities, and cognitive impairment in patients with late life BD. This review discusses common comorbidities that affect BD elders and how aging might affect cognition and treatment. METHODS: Eligible studies were identified in MedLine by the Medical Subject Headings terms "bipolar disorder" and "aged". We only included original research reports published in English between 2012 and 2015. RESULTS: From 414 articles extracted, 16 studies were included in the review. Cardiovascular and respiratory conditions, type II diabetes, and endocrinological abnormalities were observed as highly prevalent. BD is associated with a high suicide risk. Bipolar elderly had an increased risk of dementia and performed worse on cognitive screening tests compared to age matched controls across different levels of cognition. Despite high rates of medical comorbidity among bipolar elderly, a systematic under-recognition and undertreatment of cardiovascular disease have been suggested. CONCLUSION: There was a high burden of physical comorbidities and cognitive impairment in late-life BD. Bipolar elderly might be under-recorded and undertreated in primary medical care, indicating that this group needs an adapted clinical assessment and specific clinical guidelines need to be established. PMID- 27274257 TI - Clinical efficacy of perampanel for partial-onset and primary generalized tonic clonic seizures. AB - BACKGROUND AND PURPOSE: Perampanel, a selective noncompetitive antagonist at the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, is highly effective in a wide range of experimental models. Although initially licensed as adjunctive therapy for partial seizures with or without secondary generalization in patients aged 12 years or older, the US Food and Drug Administration has recently approved its use in the treatment of primary generalized tonic-clonic seizures (PGTCS). This paper reviews the pharmacokinetics, efficacy, and tolerability of perampanel as an antiepileptic drug. RESULTS: After oral ingestion, perampanel is rapidly absorbed (T max, 0.5 2.5 hours), has a bioavailability of ~100%, and is highly protein bound (~95%) in plasma. It undergoes extensive (>90%) hepatic metabolism, primarily via cytochrome P450 3A4 (CYP3A4), with a half-life of 48 hours. Carbamazepine and other antiepileptic drugs can enhance its metabolism via induction of CYP3A4. Efficacy of perampanel in focal seizures has been extensively evaluated in Phase II and randomized, placebo-controlled Phase III trials. The efficacy in PGTCS has been reported in one class I study. In the treatment of focal seizures, perampanel showed significant dose-dependent median seizure reductions: 4 mg/d, 23%; 8 mg/d, 26%-31%; 12 mg/d, 18%-35%; and placebo, 10%-21%. The 50% responder rates were 15%-26%, 29%, 33%-38%, and 34%-36% for placebo, 4 mg/d, 8 mg/d, and 12 mg/d perampanel, respectively. Freedom from seizures was recorded in 0%-1.7% of the placebo group, 1.9% of the 2 mg group, 2.6%-4.4% of the 8 mg group, and 2.6% 6.5% of the 12 mg group. For PGTCS, the median seizure reduction was 76.5% for perampanel and 38.4% for placebo. The 50% responder rate was 64.2% for perampanel and 39.5% for placebo. Seizure freedom during maintenance phase was 30.9% for perampanel and 12.3% for placebo. Adverse effects included dose-dependent increases in the frequency of dizziness, somnolence, fatigue, irritability, falls, and probably nausea. CONCLUSION: Perampanel is effective in treating both partial-onset seizures and PGTCS. PMID- 27274258 TI - Treatment response in relation to subthreshold bipolarity in patients with major depressive disorder receiving antidepressant monotherapy: a post hoc data analysis (KOMDD study). AB - BACKGROUND: The aim of this observational study was to determine whether subthreshold bipolarity affects treatment response and remission in patients with major depressive disorder receiving antidepressant (AD) monotherapy over a 6 month follow-up period. METHODS: Seventy-eight patients with major depressive disorder were stratified into two subgroups according to the presence of subthreshold bipolarity, identified using the Korean version of the Mood Disorder Questionnaire (K-MDQ), which classifies patients as positive for a screening of bipolarity based on the cutoff for the total K-MDQ score (ie, 7 points). They received AD monotherapy such as escitalopram, sertraline, paroxetine, or tianeptine for 6 months. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale, and Beck Scale for Suicide Ideation were applied at baseline, 1 week, 3 weeks, 2 months, 3 months, and 6 months. RESULTS: The mean HAMD, BDI, and Beck Scale for Suicide Ideation scores were higher in the bipolarity group than in the nonbipolarity group at 3 weeks. The mean BDI score was also higher in the bipolarity group than in the nonbipolarity group at 6 months. Evaluation of the ratio of improvement for each scale revealed different patterns of percentage changes between the two groups over the 6-month follow-up period. Furthermore, the response and remission rates (as assessed using BDI and HAMD scores) were higher in the nonbipolarity group than in the bipolarity group, with the exception of HAMD scores at the 3-week follow-up time point. CONCLUSION: The findings of this study showed that depressed patients with bipolarity had a worse response to AD monotherapy than did those without bipolarity. PMID- 27274259 TI - Microplasma radiofrequency technology combined with triamcinolone improved the therapeutic effect on Chinese patients with hypertrophic scar and reduced the risk of tissue atrophy. AB - OBJECTIVE: The current study aimed to assess the value of microplasma radiofrequency technology combined with triamcinolone for the therapy of Chinese patients with hypertrophic scar. METHODS: A total of 120 participants with hypertrophic scars were enrolled in the current study. Participants were divided into two groups based on sex, and then randomly and evenly divided into four groups (Groups A, B, C, and D). Participants in Group A received microplasma radiofrequency technology combined with triamcinolone. Participants in Group B received microplasma radiofrequency technology combined with normal saline. Participants in Groups C and D received triamcinolone (40 and 10 mg/mL) injected directly into scar. Experienced physicians evaluated the condition of scars according to the Vancouver Scar Scale 1 month before and after the therapy. RESULTS: There was no difference in age, sex, area, height and location of scars, and Vancouver Scar Scale scores before the therapy between any groups (P>0.05 for all). Vancouver Scar Scale scores after the therapy were significantly lower than those before the therapy in all groups (P<0.05 for all). Vancouver Scar Scale scores after the therapy in Group A were significantly lower than those after the therapy in Groups B and C (P<0.05 for all). Vancouver Scar Scale scores after the therapy in Group B were significantly higher than those after the therapy in Group C (P<0.05 for all) and similar to those after the therapy in Group D (P>0.05 for all). Incidences of tissue atrophy after the therapy were significantly lower in Groups A and B than in Group C (P<0.05 for all) and similar among Groups A, B, and D (P>0.05 for all). CONCLUSION: Microplasma radiofrequency technology combined with triamcinolone improved the therapeutic effect on Chinese patients with hypertrophic scar and reduced the risk of tissue atrophy compared with the use of either microplasma radiofrequency technology or triamcinolone injection alone. PMID- 27274260 TI - Recovery of a 10-year-old girl from methicillin-resistant Staphylococcus aureus sepsis in response to low-dose ceftaroline treatment. AB - A 9-year-old girl was severely injured in a car accident in Afghanistan, in which both her lower legs were badly damaged. She was treated at the Hospital of Ingolstadt (Klinikum Ingolstadt) after she had undergone initial surgery at an Indian hospital. Various bacterial species were isolated from multiple wounds, and methicillin-resistant Staphylococcus aureus (MRSA) was one among them. After the amputation of her lower legs, she developed MRSA sepsis, which was successfully treated with a relatively low dosage of ceftaroline (Zinforo((r))/Teflaro((r)); 2*9 mg/kg/d), although the bacterial isolate's minimal inhibitory concentration (1.5-4 mg/L) suggested a decreased susceptibility. In summary, ceftaroline was highly efficient and well tolerated by the patient suffering from MRSA sepsis. PMID- 27274261 TI - Association of glutathione S-transferase T1, M1, and P1 polymorphisms in the breast cancer risk: a meta-analysis. AB - BACKGROUND: Several case-control studies investigating the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, GSTT1, and GSTP1 (rs1695) and the risk of breast cancer have reported contradictory results. We therefore performed a meta-analysis to clarify this issue. MATERIALS AND METHODS: An updated meta-analysis using PubMed and Web of Knowledge databases for the eligible case-control studies was performed. Random- or fixed-effects model was used. RESULTS: A total of 10,067 cancer cases and 12,276 controls in 41 independent case-control studies from 19 articles were included in this meta analysis. Significant increase in risk of breast cancer for Asians was found in GSTM1-null genotype (P=0.012, odds ratio [OR] =1.17, 95% confidence interval [CI] =1.04-1.32) and GSTT1-null genotype (P=0.039, OR =1.19, 95% CI =1.01-1.41). In addition, our results showed that the GSTP1 (rs1695) polymorphisms can significantly increase the risk among Caucasians (P=0.042, OR =1.16, 95% CI =1.01 1.34). Sensitivity analysis and publication bias further confirmed the dependability of the results in this meta-analysis. CONCLUSION: Our results demonstrate that both GSTM1- and GSTT1-null polymorphisms are associated with an increased risk of breast cancer in Asians and that GSTP1 Val105Ile (rs1695) polymorphism is associated with an increased breast cancer risk in Caucasians. PMID- 27274262 TI - Pathophysiology of hypophosphatasia and the potential role of asfotase alfa. AB - Hypophosphatasia (HPP) is an inherited systemic bone disease that is characterized by bone hypomineralization. HPP is classified into six forms according to the age of onset and severity as perinatal (lethal), perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. The causative gene of the disease is the ALPL gene that encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP is expressed ubiquitously, and its physiological role is apparent in bone mineralization. A defect in bone mineralization can manifest in several ways, including rickets or osteomalacia in HPP patients. Patients with severe forms suffer from respiratory failure because of hypoplastic chest, which is the main cause of death. They sometimes present with seizures due to a defect in vitamin B6 metabolism resulting from the lack of alkaline phosphatase activity in neuronal cells, which is also lethal. Patients with a mild form of the disease exhibit rickets or osteomalacia and a functional defect of exercise. Odontohypophosphatasia shows only dental manifestations. To date, 302 mutations in the ALPL gene have been reported, mainly single-nucleotide substitutions, and the relationships between phenotype and genotype have been partially elucidated. An established treatment for HPP was not available until the recent development of enzyme replacement therapy. The first successful enzyme replacement therapy in model mice using a modified human TNAP protein (asfotase alfa) was reported in 2008, and subsequently success in patients with severe form of the disease was reported in 2012. In 2015, asfotase alfa was approved in Japan in July, followed by in the EU and Canada in August, and then by the US Food and Drug Administration in the USA in October. It is expected that therapy with asfotase alfa will drastically change treatments and prognosis of HPP. PMID- 27274263 TI - The effect of interferon gamma on conventional fractionated radiation-induced damage and fibrosis in the pelvic tissue of rabbits. AB - We aim to investigate the effect of interferon gamma (IFN-gamma) on conventional fractionated radiation-induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-gamma group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-gamma and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-gamma group were administered 250,000 U/kg IFN-gamma intramuscularly once a week for 5 weeks. The rabbits in the conventional radiation group received 5.0 mL/kg saline. The rabbits were sacrificed at 4, 8, 12, and 16 weeks postradiation, and the rectal and ureteral tissues within the radiation areas were collected. The results showed that the morphology of rectal and ureteral tissues was changed by X-ray radiation. The degree of damage at 4, 8, and 12 weeks, but not at 16 weeks, postradiation was significantly different between the IFN-gamma and conventional radiation groups. The expression of transforming growth factor beta 1 mRNA in the ureter and colorectal mucosa of the IFN-gamma group was significantly lower than that in the conventional radiation group at 4, 8, 12, and 16 weeks postradiation, but it was still higher than that in the control group. There were significant differences in the expression of collagen III among the three groups. IFN-gamma can inhibit the radiation-induced upregulation of transforming growth factor beta 1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuate radiation-induced damage and fibrosis. PMID- 27274264 TI - PCSK9 inhibition in the management of hyperlipidemia: focus on evolocumab. AB - Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases low-density lipoprotein cholesterol (LDL-C) concentrations through interference with normal physiologic hepatic LDL receptor (LDLR) recycling. Inhibiting PCSK9 results in improved LDLR recycling, increased LDLR availability on hepatocyte cell surfaces, and reduced blood LDL-C levels, making PCSK9 inhibition a novel therapeutic strategy for managing hypercholesterolemia. Monoclonal antibodies directed against PCSK9 have been developed for this purpose. A large number of clinical trials have demonstrated that monoclonal antibodies against PCSK9 yield substantial reductions in LDL-C when administered as monotherapy or in combination with statins to patients with nonfamilial and familial forms of hypercholesterolemia. Data from long-term trials demonstrate that the LDL-C lowering effect of PCSK9 inhibitors is durable. These agents are generally well tolerated, and few patients discontinue treatment due to adverse events. Moreover, PCSK9 inhibitors do not appear to elicit the hepatic and muscle-related side effects associated with statin use. The ultimate value of PCSK9 inhibitors will be measured by their effect on clinical outcomes. Early evidence of a reduction in cardiovascular events after 1 year of treatment was shown in a prospective exploratory analysis of two ongoing long-term open-label extension evolocumab trials. Similarly, cardiovascular events were reduced in another exploratory analysis after >1 year of therapy with alirocumab. For the primary care physician, PCSK9 inhibitors represent a welcome additional option for lowering LDL-C in patients with familial forms of hypercholesterolemia and those with clinical atherosclerotic cardiovascular disease who are on maximally tolerated statin therapy. PMID- 27274265 TI - Drug-eluting balloon catheters for lower limb peripheral arterial disease: the evidence to date. AB - A significant proportion of patients with severe lower limb peripheral arterial disease require revascularization. Over the past decade, an endovascular-first approach even for complex disease has gained widespread use among vascular specialists. An important limitation of percutaneous transluminal balloon angioplasty or stenting remains the occurrence of restenosis. Drug-coated balloons have emerged as an exciting technology developed to overcome the limitations of standard balloon angioplasty and stenting. Drug-eluting devices inhibit neointimal growth of vascular smooth muscle cells with the potential of preventing restenosis. This review provides a synopsis of the up-to-date evidence on the role of drug-coated balloons in the treatment of lower limb peripheral arterial disease. Bibliographic searches were conducted using MEDLINE, EMBASE, and the Cochrane Library electronic database. Eleven randomized clinical trials, two systematic reviews, and a published registry providing the best available evidence were identified. Current evidence suggests that angioplasty with drug coated balloon is reliable, safe, and efficient in increasing patency rates and reducing target lesion revascularization and restenosis. However, it remains unknown whether these improved results can translate into beneficial clinical outcomes, as current randomized clinical trials have failed to demonstrate a significant benefit in limb salvage and mortality. Further randomized trials focusing on clinical and functional outcomes of drug-eluting balloons and on cost versus clinical benefit are required. PMID- 27274266 TI - The effects of timing of prophylaxis, type of anesthesia, and use of mechanical methods on outcome in major orthopedic surgery - subgroup analyses from 17,701 patients in the XAMOS study. AB - PURPOSE: Real-world data on the use of rivaroxaban in the perioperative period in patients undergoing major orthopedic surgery are limited. Subsets of data from the Phase IV, non-interventional XAMOS study were analyzed to explore the potential influence of timing of the first thrombo prophylactic dose, type of anesthesia, and concomitant mechanical prophylaxis on clinical outcomes in patients undergoing major orthopedic surgery in routine clinical practice. PATIENTS AND METHODS: In XAMOS, 8,778 patients received rivaroxaban (10 mg once daily) and 8,635 received standard-of-care (SOC) pharmacological prophylaxis (safety population). Crude incidences of symptomatic thromboembolic and treatment emergent bleeding events were analyzed according to timing of the first postoperative thromboprophylactic dose, use of general or neuraxial anesthesia, and use of mechanical prophylaxis with pharmacological thromboprophylaxis. RESULTS: In the rivaroxaban group, the incidences of symptomatic thromboembolic events were 0.7%, 1.0%, and 0.7% in patients receiving the first thromboprophylactic dose at <=6 hours, >6 hours to <=10 hours, and >10 hours to <=24 hours after surgery, respectively. In the SOC group, the incidence of symptomatic thromboembolic events was slightly higher when the postoperative dose was given at >10 hours to <=24 hours (1.8% vs 1.1% at <=6 hours and 1.3% at >6 hours to <=10 hours). The antithrombotic effect of rivaroxaban was maintained in comparison to the SOC group. The incidence of major bleeding (RECORD trial definition) was low and similar between the two treatment groups and was not influenced by timing of the first thromboprophylactic dose. Neuraxial anesthesia was used more than any other form of anesthesia for both hip and knee surgery; the effectiveness of rivaroxaban was not influenced by the type of anesthesia used. No spinal hematomas were reported in patients receiving neuraxial anesthesia in either treatment group. Use of mechanical thromboprophylaxis in addition to rivaroxaban or SOC pharmacological prophylaxis did not reduce the risk of thromboembolic events further. CONCLUSION: The effectiveness and safety of rivaroxaban in patients undergoing major orthopedic surgery in routine clinical practice were maintained irrespective of timing of the first postoperative dose within 24 hours after surgery, the type of anesthesia, and the additional use of mechanical thromboprophylaxis. PMID- 27274267 TI - Scope of practice review: providers for triage and assessment of spine-related disorders. AB - PURPOSE: This study explored which health care providers could be involved in centralized intake for patients with nonspecific low back pain to enhance access, continuity, and appropriateness of care. METHODS: We reviewed the scope of practice regulations for a range of health care providers. We also conducted telephone interviews with 17 individuals representing ten provincial colleges and regulatory bodies to further understand providers' legislated scopes of practice. Activities relevant to triaging and assessing patients with low back pain were mapped against professionals' scope of practice. RESULTS: Family physicians and nurse practitioners have the most comprehensive scopes and can complete all restricted activities for spine assessment and triage, while the scope of registered nurses and licensed practical nurses are progressively narrower. Chiropractors, occupational therapists, physiotherapists, and athletic therapists are considered experts in musculoskeletal assessments and appear best suited for musculoskeletal specific assessment and triage. Other providers may play a complementary role depending on the individual patient needs. CONCLUSION: These findings indicate that an interprofessional assessment and triage team that includes allied health professionals would be a feasible option to create a centralized intake model. Implementation of such teams would require removing barriers that currently prevent providers from delivering on their full scope of practice. PMID- 27274268 TI - Describing the characteristics, treatment pathways, outcomes, and costs of people with persistent noncancer pain managed by community pain clinics and generating an indicative estimate of cost-effectiveness: feasibility study protocol. AB - BACKGROUND: Low back pain (LBP) and fibromyalgia (FM), also known as chronic widespread pain (CWP), are highly prevalent chronic painful conditions that have substantial impact on patients, health care systems, and society. Diagnosis is complex and management strategies are associated with various levels of evidence for effectiveness and cost-effectiveness. Multidisciplinary pain services have been shown to be effective in some settings and therefore are recommended by clinical practice guidelines as a rational treatment option to manage these patients. Knowing that these services are resource intensive, evidence is needed to demonstrate their cost-effectiveness. This study aims to describe the management of patients with LBP and FM in two community pain clinics to derive an indicative estimate of cost-effectiveness compared with standard practice. METHODS: This is a prospective observational multicenter study, using patient level data. The data from this study will be combined with modelling of the long term economic impact of community pain clinics in treating people with LBP and FM. Newly referred patients with LBP and FM who provide written consent will be included. We will collect data on functional disability, pain intensity, quality of life, and health resource utilization. Follow-up data at the 3- and 6-month points will be collected by patient-completed questionnaires and health care contact diaries. Health care resource use from diaries will be compared with patient electronic records to assess the agreement between these recording methods. Patient cohort characteristics, treatment pathways, resource use, and outcomes derived from this study will be integrated in a decision analysis model to assess the cost-effectiveness of community pain clinics compared with standard care. This feasibility study will address key methodological issues such as sample estimates and retention rate to inform the design of a future randomized controlled trial. PMID- 27274269 TI - HOXB7 as a promising molecular marker for metastasis in cancers: a meta-analysis. AB - Numerous studies on carcinoma have revealed that the expression level of HOXB7 in cancerous tissues was significantly higher than that in noncancerous tissues. Elevated expression of HOXB7 is associated with the susceptibility to lymph node metastasis and distant metastasis in various tumors. In this study, a meta analysis was performed to involve majority of relevant articles and explore the association of HOXB7 expression level with metastasis in cancer patients. Literature retrieval was conducted by searching in a number of electronic databases (up to December 1, 2015). The meta-analysis was conducted with RevMan 5.3 software and Stata SE12.0. A total of 1,532 patients with carcinoma from 14 studies were included in analysis. The results of meta-analysis demonstrated that lymph node metastasis was observed more frequently in the patients group with high expression level of HOXB7 than in the patients group with low expression level of HOXB7 (odds ratio =2.17, 95% CI: 1.74-2.71, P<0.00001, fixed-effects model). In addition, a similar result was observed in the association between HOXB7 expression and distant metastasis; the odds ratio was 1.77 (95% CI: 1.09 2.88, P=0.02, fixed-effects model). This meta-analysis demonstrated that the overexpression of HOXB7 was significantly associated with metastasis in cancer patients, which may be served as a common molecular marker for indicating cancer metastasis. PMID- 27274270 TI - Orbital metastasis as the initial presentation of lung adenocarcinoma: a case report. AB - Orbital metastasis as the initial presentation of lung adenocarcinoma is very rare, and so the lack of knowledge about this phenomenon can easily result in misdiagnosis, either as a orbital primary tumor or benign lesion. Here, we report a rare case in which the orbital symptom appeared first without any pulmonary manifestations. Our patient developed decreasing vision in his right eye over a 3 month duration. He then presented with proptosis and multiple aches from head to back. After systemic evaluation, our patient was diagnosed with Stage IV non small-cell lung cancer and was managed with palliative chemoradiotherapy. The final result of treatment suggests that the therapeutic efficacy of chemotherapy on orbital metastasis is uncertain, and only some orbital metastatic masses may have a favorable response to radiation. Furthermore, we review the recent data and provide an in-depth discussion on the clinical features and course of ocular pulmonary metastases, and explain a new type of non-small-cell lung cancer metastatic pattern for ophthalmologists and oncologists to help them distinguish the orbital metastasis as the first manifestation. PMID- 27274271 TI - Single-nucleotide polymorphism in microRNA-binding site of SULF1 target gene as a protective factor against the susceptibility to breast cancer: a case-control study. AB - PURPOSE: Numerous clinical studies have suggested that chemopreventive drugs for breast cancer such as tamoxifen and exemestane can effectively reduce the incidence of estrogen receptor (ER)-positive breast cancer. However, it remains unclear how to identify those who are susceptible to ER-positive breast cancer. Accordingly, there is a great demand for a probe into the predisposing factors so as to provide precise chemoprevention. Recent evidence has indicated that ERalpha expression can be regulated by microRNAs (miRNAs), such as miR-206, in breast cancer. We assumed that single-nucleotide polymorphisms (SNPs) in the miR-206 binding sites of the target genes may be associated with breast cancer susceptibility with different ER statuses. METHODS: We genotyped the SNPs that reside in and around the miR-206-binding sites of two target genes - heparan sulfatase 1 (SULF1) and RPTOR-independent companion of mammalian target of rapamycin Complex 2 (RICTOR) - which were related to the progression or metastasis of breast cancer cells in 710 breast cancer patients and 294 controls by the matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Modified odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated by a multivariate logistic regression analysis to evaluate the potential association between the SNPs and breast cancer susceptibility. RESULTS: For rs3802278, which is located in the 3'-untranslated region (3'-UTR) of SULF1, the frequency of the AA genotype was less in breast cancer patients than that in the controls as compared to that of the GG + GA genotype not only for ER-positive breast cancer patients (adjusted OR =0.663, P=0.032) but also for hormone receptor-positive breast cancer patients (adjusted OR =0.610, P=0.018). Besides, the frequency of the AA genotype was less than that of the GG genotype between the ER-positive breast cancer patients and the controls (adjusted OR =0.791, P=0.038). For rs66916453, which is located in the 3'-UTR of RICTOR, no significant difference was observed between the case and the control group for the genotypes or alleles (P>0.05). CONCLUSION: The SNPs in the miRNA-binding sites within the 3'-UTR of SULF1 may serve as protective factors against the susceptibility to breast cancer, especially to ER-positive breast cancer in the Chinese population. These SNPs are promising candidate biomarkers to predict the susceptibility of breast cancer and guide the administration of targeted preventive endocrine therapy. PMID- 27274272 TI - Prognostic significance of lymphocyte-to-monocyte ratio and CRP in patients with nonmetastatic clear cell renal cell carcinoma: a retrospective multicenter analysis. AB - BACKGROUND: Inflammation has been reported to be involved in carcinogenesis and cancer progression. This study was designed to explore the prognostic significance of lymphocyte-to-monocyte ratio (LMR) and serum C-reactive protein (CRP) in nonmetastatic clear cell renal cell carcinoma (ccRCC) patients after treatment. METHODS: The retrospective study consisted of 985 patients with ccRCC who had undergone nephrectomy from 2005 to 2010 at multiple centers. The patients were divided into four groups using a quartile of LMR or CRP, and their associations with clinical characteristics and outcome were systematically estimated. RESULTS: Both low LMR and high CRP significantly diminished overall survival (OS) and metastasis-free survival (MFS) in patients with ccRCC. Further investigation indicated that LMR and CRP were independent prognostic factors of both OS and MFS. Integration of LMR and CRP into a predictive model, including significant variables in multivariate analysis, established a nomogram to predict accurately the 3- and 5-year survival for nonmetastatic patients with ccRCC. CONCLUSION: LMR and CRP represent independent prognostic factors of OS and MFS for patients with ccRCC. Incorporation of LMR and CRP into the traditional TNM staging system may improve their predictive performance. PMID- 27274274 TI - Clinical developments in the treatment of relapsed or relapsed and refractory multiple myeloma: impact of panobinostat, the first-in-class histone deacetylase inhibitor. AB - BACKGROUND: Panobinostat is a new agent for the treatment of relapsed and refractory multiple myeloma (rrMM) as part of a combination regimen. This article presents an overview of the mechanism of action, pharmacokinetics, safety, efficacy, patient care strategies, and role of the agent in treating rrMM patients. RESULTS: Panobinostat belongs to the class of drugs known as histone deacetylase inhibitors, and has high activity against Class I, II, and IV nonhistone deacetylases and histone deacetylases. It represents the first of its class to receive approval for use in MM, and received priority review and orphan drug status in both US and Europe, when used in combination with bortezomib and dexamethasone in the treatment of rrMM. Approval of panobinostat was based on subgroup analysis of Phase III data obtained in the PANORAMA trial program for evaluation of the combination of panobinostat, bortezomib, and dexamethasone. Additional clinical trials have continued to explore optimal dosing regimens and novel combination regimens to further clarify the optimal role of panobinostat in the arsenal of drugs for rrMM. Panobinostat has shown a manageable safety profile characterized primarily by hematologic toxicities (thrombocytopenia, neutropenia, lymphopenia, and anemia), gastrointestinal toxicities, notably diarrhea and nausea, as well as fatigue/asthenia, electrolyte abnormalities, and less commonly cardiac toxicities. CONCLUSION: Panobinostat represents an important addition to the treatment armamentarium for patients with rrMM, and studies are underway evaluating its optimal dosing strategy and role in combination with other drugs used to treat this patient population. PMID- 27274275 TI - Silencing of carboxypeptidase E inhibits cell proliferation, tumorigenicity, and metastasis of osteosarcoma cells. AB - Carboxypeptidase E (CPE), a prohormone processing enzyme, has been implicated in the progression of multiple malignancies. However, the biological role and molecular mechanisms of CPE in osteosarcoma remain elusive. In this study, we assessed the effects of CPE on cell proliferation, tumorigenicity, migration, and invasion in osteosarcoma. Our results showed that silencing of CPE significantly inhibited cell proliferation, caused cell cycle arrest at G0/G1 phase, decreased the expression levels of cell cycle protein, cyclin D1, and inhibited tumorigenicity in vivo. Additionally, CPE downregulation repressed the migratory and invasive capacities of osteosarcoma cells in vitro. Furthermore, overexpression of CPE-DeltaN (a splice variant of CPE) enhanced the cell growth, migration, and invasion of osteosarcoma cells. It is possible that both CPE forms are involved in the tumorigenesis and development of osteosarcoma, and therefore CPE may provide a promising biological target for osteosarcoma therapy. PMID- 27274273 TI - Design, synthesis, and evaluation of cisplatin-containing EGFR targeting bioconjugates as potential therapeutic agents for brain tumors. AB - The aim of this study was to evaluate four different platinated bioconjugates containing a cisplatin (cis-diamminedichloroplatinum [cis-DDP]) fragment and epidermal growth factor receptor (EGFR)-targeting moieties as potential therapeutic agents for the treatment of brain tumors using a human EGFR expressing transfectant of the F98 rat glioma (F98EGFR) to assess their efficacy. The first two bioconjugates employed the monoclonal antibody cetuximab (C225 or Erbitux((r))) as the targeting moiety, and the second two used genetically engineered EGF peptides. C225-G5-Pt was produced by reacting cis-DDP with a fifth generation polyamidoamine dendrimer (G5) and then linking it to C225 by means of two heterobifunctional reagents. The second bioconjugate (C225-PG-Pt) employed the same methodology except that polyglutamic acid was used as the carrier. The third and fourth bioconjugates used two different EGF peptides, PEP382 and PEP455, with direct coordination to the Pt center of the cis-DDP fragment. In vivo studies with C225-G5-Pt failed to demonstrate therapeutic activity following intracerebral (ic) convection-enhanced delivery (CED) to F98EGFR glioma-bearing rats. The second bioconjugate, C225-PG-Pt, failed to show in vitro cytotoxicity. Furthermore, because of its high molecular weight, we decided that lower molecular weight peptides might provide better targeting and microdistribution within the tumor. Both PEP382-Pt and PEP455-Pt bioconjugates were cytotoxic in vitro and, based on this, a pilot study was initiated using PEP455-Pt. The end point for this study was tumor size at 6 weeks following tumor cell implantation and 4 weeks following ic CED of PEP455-Pt to F98 glioma-bearing rats. Neuropathologic examination revealed that five of seven rats were either tumor free or only had microscopic tumors at 42 days following tumor implantation compared to a mean survival time of 20.5 and 26.3 days for untreated controls. In conclusion, we have succeeded in reformatting the toxicity profile of cis-DDP and demonstrated the therapeutic efficacy of the PEP455-Pt bioconjugate in F98 glioma bearing rats. PMID- 27274276 TI - Sophoridinol derivative 05D induces tumor cells apoptosis by topoisomerase1 mediated DNA breakage. AB - Sophoridine is a quinolizidine natural product of Sophora alopecuroides and has been applied for treatment of malignant trophoblastic tumors. Although characterized by low toxicity, the limited-spectrum antitumor activity hinders its further applications. 05D, a derivative of sophoridine, exhibits a better anticancer activity on diverse cancer cells, including solid tumors, and hematologic malignancy. It could inhibit topoisomerase 1 (top1) activity by stabilizing DNA-top1 complex and induce mitochondria-mediated apoptosis by promoting DNA single- and double-strand breakage mediated by top1. Also, 05D induced HCT116 cells arrest at G1 phase by inactivating CDK2/CDK4-Rb-E2F and cyclinD1-CDK4-p21 checkpoint signal pathways. 05D suppressed the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) activation and decreased 53BP level, which contributed to DNA damage repair, suggesting that the novel compound 05D might be helpful to improve the antitumor activity of DNA damaging agent by repressing ATM and ATR activation and 53BP level. In addition, the priorities in molecular traits and druggability, such as a simple structure and formulation for oral administration, further prove 05D to be a promising targeting topoisomerase agent. PMID- 27274277 TI - Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation? AB - AIM: Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. PATIENTS AND METHODS: Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. RESULTS: In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. CONCLUSION: There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID- 27274278 TI - Sodium phenylbutyrate antagonizes prostate cancer through the induction of apoptosis and attenuation of cell viability and migration. AB - BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer-related death in men. Sodium phenylbutyrate (SPB) has shown its potential as an anticancer therapy in numerous cancer types. In the present study, we attempted to assess the effect of SPB against PCa and whether this treatment was associated with the regulation of survivin. METHODS: Two human PCa cancer cell lines, DU145 and PC3, were used in the present study. Cell Counting Kit-8 (CCK-8) assay was conducted to measure the proliferation of PCa cells incubated with SPB. The effect of SPB on the cell apoptosis, cell colony formation ability, and cell morphological change was also assessed. Transwell experiment and Western blotting assay were performed to determine the effect of SPB on the migration and invasion ability of both cell types. Moreover, the expression pattern of survivin and MAPK members in both cell types after the treatment of SPB was also detected. Additionally, an in vivo tumor formation assay was performed to evaluate the treatment potential of SPB against PCa. RESULTS: We found that the viability of PCa cells was significantly inhibited by SPB treatment. As illustrated by flow cytometry, for DU145 cell line the average apoptotic rate of SPB-treated cells was significantly lower than that of the control group (P<0.05); similar results were also seen for PC3 (P<0.05). SPB administration also attenuated the colony formation and migration abilities in both cell lines. The expression level of survivin in SPB-treated cells was significantly downregulated, while the phosphorylation of p-38 and ERK was enhanced. Furthermore, in vivo tumor formation of both cell lines was suppressed by SPB as well. CONCLUSION: The above results confirmed the potential of SPB as an effective therapeutic agent for the prevention or treatment of PCa. This amelioration might be due to the blockade of the survivin pathway. PMID- 27274279 TI - Transcatheter arterial embolization combined with radiofrequency ablation activates CD8(+) T-cell infiltration surrounding residual tumors in the rabbit VX2 liver tumors. AB - PURPOSE: To evaluate the effect of transcatheter arterial embolization (TAE) combined with radiofrequency ablation (RFA) treatment (TAE + RFA) on the expression of heat shock protein 70 (HSP70) in residual tumors and explore the relationship between the HSP70 and CD8(+) T-cell infiltrate surrounding residual tumors in the rabbit VX2 liver tumor model. MATERIALS AND METHODS: Animals with VX2 liver tumors were randomized into four groups (control, TAE, RFA, and TAE + RFA) with 15 rabbits in each group. Five rabbits in each group were sacrificed on days 1, 3, and 7 after treatment. HSP70 expression and infiltration of CD8(+) T cells in the liver and residual tumors surrounding the necrosis zone were detected by immunohistochemistry staining. The maximal diameters of tumor necrosis, numbers of metastases, and tumor growth rate were compared on day 7 after treatment. RESULTS: TAE + RFA achieved larger maximal diameter of tumor necrosis, lower tumor growth rate, and fewer metastatic lesions, compared with other treatments on day 7. The number of CD8(+) T-cells in the TAE + RFA group was significantly higher than in other groups on days 1, 3, and 7. There was a positive correlation between HSP70 expression level and infiltration of CD8(+) T cells surrounding the residual tumor on day 1 (r=0.9782, P=0.012), day 3 (r=0.93, P=0.021), and day 7 (r=0.8934, P=0.034). CONCLUSION: In the rabbit VX2 liver tumor model, TAE + RFA activated the highest number of CD8(+) T-cells surrounding residual tumors. TAE + RFA appears to be a beneficial therapeutic modality for tumor control and antitumor immune response in this model. PMID- 27274280 TI - Metformin induces apoptosis of human hepatocellular carcinoma HepG2 cells by activating an AMPK/p53/miR-23a/FOXA1 pathway. AB - The antidiabetic drug metformin has been shown to possess antitumor functions in many types of cancers. Although studies have revealed its beneficial effects on the prognosis of hepatocellular carcinoma (HCC), the detailed molecular mechanism underlying this event remains largely unknown. In this work, we showed that miR 23a was significantly induced upon metformin treatment; inhibition of miR-23a abrogated the proapoptotic effect of metformin in HepG2 cells. We next established forkhead box protein A1 (FOXA1) as the functional target of miR-23a, and silencing FOXA1 mimicked the effect of metformin. Moreover, the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of p53 were increased upon metformin treatment, and the inhibition of p53 abrogated the induction of miR-23a by metformin, suggesting that AMPK/p53 signaling axis is responsible for the induction of miR-23a by metformin. In summary, we unraveled a novel AMPK/p53/miR-23a/FOXA1 axis in the regulation of apoptosis in HCC, and the application of metformin could, therefore, be effective in the treatment of HCC. PMID- 27274281 TI - Evaluation of response from axitinib per Response Evaluation Criteria in Solid Tumors versus Choi criteria in previously treated patients with metastatic renal cell carcinoma. AB - BACKGROUND: Axitinib, a selective and potent tyrosine kinase inhibitor of vascular endothelial growth factor receptors, was available to patients from Canada and Australia, prior to regulatory approval of axitinib in these countries, for treatment of clear-cell metastatic renal cell carcinoma (mRCC) after failure of one prior systemic regimen. METHODS: This single-arm, open-label study of axitinib evaluated the efficacy, safety, and quality of life (QoL) in patients with mRCC whose disease progressed after one prior systemic first-line regimen. Primary objective was objective response rate evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) and Choi criteria. Progression-free survival, overall survival, safety, and QoL were secondary end points. Due to the small study size, analyses comprised of descriptive statistics. RESULTS: Fifteen patients were recruited, five from Canada and ten from Australia, over a limited recruitment period. Thirteen patients received sunitinib as prior therapy. All patients had clear-cell carcinoma, eleven had prior nephrectomy. Liver, lung, and lymph nodes were the most frequent sites of metastases; one patient had brain metastasis. Median time on axitinib was 118.0 days (range: 3.5-645.0 days); estimated survival probability at 12 months was 57.8%. Two (13.3%) patients had objective responses per RECIST versus nine (60.0%) per Choi criteria. Six patients had progressive disease based on RECIST versus three per Choi criteria. Nine (60.0%) events of progression or death occurred by the end of study, and three patients continued to receive the study drug. Fatigue (33%) and diarrhea (20%) were the most common grade >=3 all-causality, treatment-emergent adverse events. The mean change in European Quality of Life - 5 Dimensions score from baseline to end of treatment was -0.0837. CONCLUSION: The small number of patients and lack of a comparator arm limit the ability to draw definitive conclusions; however, safety and efficacy profiles of axitinib were consistent with reports from previous studies in patients with mRCC, and patients generally maintained QoL. The sizeable difference observed in objective response rate by RECIST versus Choi criteria merits further research. PMID- 27274283 TI - Comparative effects of different enteral feeding methods in head and neck cancer patients receiving radiotherapy or chemoradiotherapy: a network meta-analysis. AB - Nasogastric tube (NGT) and percutaneous endoscopic gastrostomy were frequently used in the head and neck cancer patients when malnutrition was present. Nevertheless, the evidence was inclusive in terms of the choice and the time of tube placement. The aim of this network meta-analysis was to evaluate the comparative effects of prophylactic percutaneous endoscopic gastrostomy (pPEG), reactive percutaneous endoscopic gastrostomy (rPEG), and NGT in the head and neck cancer patients receiving radiotherapy or chemoradiotherapy. Databases of PubMed, Web of Science, and Elsevier were searched from inception to October 2015. Thirteen studies enrolling 1,631 participants were included in this network meta analysis. The results indicated that both pPEG and NGT were superior to rPEG in the management of weight loss. pPEG was associated with the least rate of treatment interruption and nutrition-related hospital admission among pPEG, rPEG, and NGT. Meanwhile, there was no difference in tube-related complications. Our study suggested that pPEG might be a better choice in malnutrition management in the head and neck cancer patients undergoing radiotherapy or chemoradiotherapy. However, its effects need to be further investigated in more randomized controlled trials. PMID- 27274282 TI - Recent advancements in erythrocytes, platelets, and albumin as delivery systems. AB - In the past few years, nanomaterial-based drug delivery systems have been applied to enhance the efficacy of therapeutics and to alleviate negative effects through the controlled delivery of targeting and releasing agents. However, few drug carriers can achieve high targeting efficacy, even when targeting modalities and surface markers are introduced. Immunological problems have also limited their wide applications. Biological drug delivery systems, such as erythrocytes, platelets, and albumin, have been extensively investigated because of their unique properties. In this review, erythrocytes, platelets, and albumin are described as efficient drug delivery systems. Their properties, applications, advantages, and limitations in disease treatment are explained. This review confirms that these systems can be used to facilitate a specific, biocompatible, and smart drug delivery. PMID- 27274284 TI - Efficacy and safety of icotinib in patients with brain metastases from lung adenocarcinoma. AB - OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of icotinib in patients with brain metastases (BMs) from lung adenocarcinoma. PATIENTS AND METHODS: Clinical data of 28 cases with BMs from lung adenocarcinoma were retrospectively analyzed. All the patients took 125 mg icotinib orally three times a day. Progression of disease, intolerable adverse reactions, and number of deaths were recorded. RESULTS: For all the patients, the remission rate of icotinib was 67.8% and the disease control rate was 96.4%. The median overall survival time of patients was 21.2 months, and the median progression-free survival time of patients was 10.9 months. Only mild adverse events of grade 1/2 were observed during the treatment. CONCLUSION: Icotinib was an effective and safe strategy to treat patients with BMs from lung adenocarcinoma. PMID- 27274285 TI - PIM1 polymorphism and PIM1 expression as predisposing factors of esophageal squamous cell carcinoma in the Asian population. AB - Our study aimed to identify the association between a PIM1 polymorphism and PIM1 expression levels with clinicopathological features of esophageal squamous cell carcinoma (ESCC). A total of 168 patients with ESCC were recruited as the case group, and 180 healthy individuals were included as the control group. Polymerase chain reaction-direct sequencing was employed to analyze all genotypes containing the PIM1 -1 882 A>T mutation. Immunohistochemistry was used to detect PIM1 expression. The distributions of genotype AA and allele A of PIM1 -1 882 A>T were higher in the case group than in the control group (both P<0.05). AT + TT carriers had a lower risk of ESCC than AA carriers (P<0.05). PIM1 polymorphism was related to the invasion depth, degree of differentiation, and lymphatic metastasis of ESCC (P<0.05). PIM1 expression was associated with lymphatic metastasis of ESCC and PIM1 polymorphism (both P<0.05). PIM1 -1 882 A>T and the overexpression of PIM1 were associated with the clinicopathological features of ESCC, and PIM1 -1 882 A>T may help to reduce the risk of ESCC in the Asian population. PMID- 27274287 TI - Advances of wogonin, an extract from Scutellaria baicalensis, for the treatment of multiple tumors. AB - As the major bioactive compound of Scutellaria baicalensis that has been approved to be effective as an anti-inflammatory and antiviral inhibitor in cardiovascular diseases, wogonin (WG) showed potent and promising antitumor effects both in vitro and in vivo. It has been proved that WG has the ability to inhibit the growth of tumor cells, induce apoptosis, and suppress angiogenesis. The molecular mechanisms involve reactive oxygen species, Ca(2+), NF-kappaB, tumor necrosis factor-related apoptosis-inducing ligand, and tumor necrosis factor-alpha. Furthermore, the synergistic effect of WG with 5-fluorouracil, etoposide, and adriamycin to enhance chemotherapy and reverse drug resistance has also been confirmed. In this review, we summarize the advances in recent years on the antitumor effect of WG on multiple tumors; in addition, we also present information regarding the synergistic and chemosensitizing effects of WG with other drugs to illustrate its potential use in the clinic. PMID- 27274286 TI - The association of the CYP1A1 Ile462Val polymorphism with head and neck cancer risk: evidence based on a cumulative meta-analysis. AB - OBJECTIVE: The aim of this study was to address the association between the Ile462Val polymorphism in the gene encoding cytochrome P450 1A1 (CYP1A1) and the risk of head and neck cancer (HNC). MATERIALS AND METHODS: The Medline/PubMed, EMBASE, and Web of Science databases were searched. The strength of the association was evaluated by calculating the odds ratio (OR) with a 95% confidence interval (CI). RESULTS: Overall, we observed an increased risk of HNC in patients with the Ile/Val+Val/Val genotype compared to those with the Ile/Ile genotype among the 6,367 cases and 6,395 controls evaluated in the 34 eligible studies, with a pooled OR of 1.284 (95% CI: 1.119-1.473). In addition, we observed an increased risk of HNC in patients with the Ile/Val+Val/Val genotype compared to those with the Ile/Ile genotype in the subgroup analyses (OR =1.362, 95% CI: 1.102-1.685 for laryngeal cancer; OR =1.519, 95% CI: 1.253-1.843 for pharyngeal cancer; OR =1.371, 95% CI: 1.111-1.693 for Asians; and OR =1.329, 95% CI: 1.138-1.551 for patients in studies using hospital-based controls). CONCLUSION: This cumulative meta-analysis suggests that the CYP1A1 Ile462Val polymorphism might contribute to the risk of HNC, particularly for pharyngeal cancer and laryngeal cancer. PMID- 27274288 TI - Idelalisib for the treatment of indolent non-Hodgkin lymphoma: a review of its clinical potential. AB - Idelalisib is a first-in-class, oral, selective phosphatidylinositol 3-kinase delta inhibitor that offers a chemotherapy-free option for patients with relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). Clinical trials in iNHL have evaluated idelalisib as monotherapy and as combination therapy with rituximab, bendamustine, and rituximab + bendamustine. When administered to heavily pretreated patients with R/R iNHL, idelalisib monotherapy or combination therapy showed durable antitumor activity accompanied by sustained or improved quality-of-life outcomes. Idelalisib has an acceptable safety profile; however, serious or fatal diarrhea/colitis, hepatoxicity, pneumonitis, and intestinal perforation have occurred in treated patients. Selective inhibition of phosphatidylinositol 3-kinase delta with idelalisib is a valuable addition to available treatment options for patients with iNHL, many of whom do not respond to or cannot tolerate chemoimmunotherapy. Two Phase III, randomized, placebo controlled trials of idelalisib as combination therapy with rituximab or bendamustine + rituximab and a Phase I trial of idelalisib in combination with the Bruton's tyrosine kinase inhibitor ONO/GS-4059 in R/R B-cell malignancies are currently ongoing. A Phase III monotherapy trial in previously treated follicular lymphoma or small lymphocytic lymphoma is planned. The development of other kinase inhibitors for the treatment of iNHL raises the potential for new treatment combinations. Additional research is needed to determine optimal therapy (monotherapy vs combination regimens), treatment sequencing, and long term management. PMID- 27274289 TI - Low-grade nasopharyngeal papillary adenocarcinoma: a case report and review of the literature. AB - Low-grade nasopharyngeal papillary adenocarcinoma is an extremely rare tumor, with only a limited number of cases reported in the literature. Some published studies have paid more attention to the clinicopathological features of nasopharyngeal adenocarcinoma, while little effort has been made to study the optimal therapeutic strategies. We report about a woman diagnosed with low-grade nasopharyngeal papillary adenocarcinoma. She received the treatment approach that combined transnasal endoscopic surgery to remove the lesion with postoperative radiotherapy for nasal cavity. There was no evidence of recurrence after 4 months of surgery, and further follow-up is being continued. Through this example, we wanted to explore the optimal therapeutic strategies for primary nasopharyngeal adenocarcinomas. PMID- 27274290 TI - Economic burden of refractory chronic spontaneous urticaria on Kuwait's health system. AB - BACKGROUND: Chronic spontaneous urticaria (CSU) is a common problem worldwide. We evaluated the direct medical costs of treating patients with refractory CSU and the budget effect of omalizumab use in these patients in Kuwait. METHODS: The prevalence of CSU was estimated using the Delphi method. Medical records of patients with refractory CSU in Kuwait were reviewed. Costs were calculated from a health system perspective. One-way sensitivity analyses were conducted on the price and utilization of each cost component. RESULTS: Before omalizumab use, the total direct costs of treating 1,293 patients with refractory CSU were estimated to be USD 3,650,733 per year. This estimation was principally generated by outpatient visits. After omalizumab use, the cost was sensitive to price variation and estimated to be USD 15,828,612 per year. All other direct costs were reduced. CONCLUSION: The economic burden of refractory CSU in Kuwait is high. Omalizumab use is costly, but its administration reduces all other direct costs. PMID- 27274291 TI - The economic impact of educational training assessed by the Handling Questionnaire with three inhalation devices in asthma and Chronic Obstructive Pulmonary Disease patients. AB - BACKGROUND: The usability of inhalation devices depends on several factors, eg, the drug to inhale, device handling, and patients' training. Usability is then presumed to have economic consequences. AIM: To assess and compare the cost of patients' training for proper usability of Breezhaler and Genuair (both dry powder inhalers) and Respimat (a soft mist inhaler) in asthma and chronic obstructive pulmonary disease (COPD) outpatients. METHODS: The acceptance and handling of the three devices were investigated by means of the Handling Questionnaire. The time spent in specific training for ensuring a proper actuation and the corresponding costs were also calculated. Linear and logistic regressions were used in order to investigate the factors influencing proper handling of the devices. A significance level of P<0.05 was accepted. RESULTS: According to both the patients' and the nurse's judgments, Genuair and Respimat were perceived as the easiest devices to use, while Breezhaler required the highest number of attempts for achieving the first proper actuation (2.6 vs 1.6; P<0.0001). The total training cost per patient (including the nurse's time for demonstration and that for attending the patients' maneuvers) was ?1.38+/-?1.21. Breezhaler was found to be the most expensive as the cost per patient was ?2.35+/ ?1.26, which was three to four times higher than that of Genuair and Respimat (both devices involved a cost of 80%). The estimated budget impact range of D ER was $0.014-$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P<0.0001) and other outpatient visits (22.8% vs 51.4%, P<0.0001) over the 12-month follow-up. Changes in HRU from follow-up to baseline were lower in the D-ER cohort for metrics including walking-impairment-related hospitalizations and emergency department visits. CONCLUSION: The majority of D-ER patients were adherent to treatment. D-ER utilization was associated with fewer walking-impairment-related physician and outpatient visits, with lower HRU increase over time. The budget impact of D-ER was low. PMID- 27274293 TI - Prolonged length of stay associated with air leak following pulmonary resection has a negative impact on hospital margin. AB - BACKGROUND: Protracted hospitalizations due to air leaks following lung resections are a significant source of morbidity and prolonged hospital length of stay (LOS), with potentially significant impact on hospital margins. This study aimed to evaluate the relationship between air leaks, LOS, and financial outcomes among discharges following lung resections. MATERIALS AND METHODS: The Medicare Provider Analysis and Review file for fiscal year 2012 was utilized to identify inpatient hospital discharges that recorded International Classification of Diseases (ICD-9) procedure codes for lobectomy, segmentectomy, and lung volume reduction surgery (n=21,717). Discharges coded with postoperative air leaks (ICD 9-CM codes 512.2 and 512.84) were defined as the air leak diagnosis group (n=2,947), then subcategorized by LOS: 1) <7 days; 2) 7-10 days; and 3) >=11 days. Median hospital charges, costs, payments, and payment-to-cost ratios were compared between non-air leak and air leak groups, and across LOS subcategories. RESULTS: For identified patients, hospital charges, costs, and payments were significantly greater among patients with air leak diagnoses compared to patients without (P<0.001). Hospital charges and costs increased substantially with prolonged LOS, but were not matched by a proportionate increase in hospital payments. Patients with LOS <7, 7-10, and >=11 days had median hospital charges of US $57,129, $73,572, and $115,623, and costs of $17,594, $21,711, and $33,786, respectively. Hospital payment increases were substantially lower at $16,494, $16,307, and $19,337, respectively. The payment-to-cost ratio significantly lowered with each LOS increase (P<0.001). Higher inpatient hospital mortality was observed among the LOS >=11 days subgroup compared with the LOS <11 days subgroup (P<0.001). CONCLUSION: Patients who develop prolonged air leaks after lobectomy, segmentectomy, or lung volume reduction surgery have the best clinical and financial outcomes. Hospitals experience markedly lower payment-to-cost ratios as LOS increases. Interventions minimizing air leak or allowing outpatient management will improve financial performance and hospital margins for lung surgery. PMID- 27274294 TI - Metabolic syndrome and C-reactive protein in bank employees. AB - BACKGROUND: The ultrasensitive C-reactive protein (us-CRP) is used for the diagnosis of cardiovascular disease, but it is not well described as a marker for the diagnosis of metabolic syndrome (MS). METHODS: An observational and transversal study of bank employees evaluated anthropometric, hemodynamic, and biochemical data. CRP values were determined using commercial kits from Roche Diagnostics Ltd, and MS criteria were analyzed according to National Cholesterol Education Program's - Adult Treatment Panel III (NCEP/ATP III). RESULTS: A total of 88 individuals had MS, and 77.3% (n=68) of these showed alterations of us-CRP (P=0.0001, confidence interval [CI] 0.11-0.34). Individuals with MS had higher mean values of us-CRP in global measures (P=0.0001) and stratified by sex (P=0.004) than individuals without the syndrome. This marker exhibited significant differences with varying criteria for MS, such as waist circumference (P=0.0001), triglycerides (P=0.002), and diastolic blood pressure (P=0.007), and the highest levels of us-CRP were found in individuals with more MS criteria. CONCLUSION: us-CRP was strongly associated with the presence of MS and MS criteria in this group of workers. us-CRP is a useful and effective marker for identifying the development of MS and may be used as a reference in routine care. PMID- 27274296 TI - Depression in diabetic patients attending University of Gondar Hospital Diabetic Clinic, Northwest Ethiopia. AB - BACKGROUND: Diabetes mellitus, frequently associated with comorbid depression, contributes to the double burden of individual patients and community. Depression remains undiagnosed in as many as 50%-75% of diabetes cases. This study aimed to determine the prevalence and associated factors of depression among diabetic patients attending the University of Gondar Hospital Diabetic Clinic, Northwest Ethiopia. METHODS: An institution-based cross-sectional study was conducted from March to May 2014 among 422 sampled diabetic patients attending the University of Gondar Hospital Diabetic Clinic. The participants were selected using systematic random sampling. Data were collected by face-to-face interview using a standardized and pretested questionnaire linked with patient record review. Depression was assessed using the Patient Health Questionnaire-9. Data were entered to EPI INFO version 7 and analyzed by SPSS version 20 software. Binary logistic regression analysis was performed to identify factors associated with depression. RESULTS: A total of 415 diabetic patients participated in the study with a response rate of 98.3%. The prevalence of depression among diabetic patients was found to be 15.4% (95% confidence interval (CI): 11.7-19.2). Only religion (adjusted odds ratio [AOR] =2.65 and 95% CI: 1.1-6.0) and duration of diabetes (AOR =0.27 and 95% CI: 0.07-0.92) were the factors associated with depression among diabetic patients. CONCLUSION: The prevalence of depression was low as compared to other similar studies elsewhere. Disease (diabetes) duration of 10 years and above and being a Muslim religion follower (as compared to Christian) were the factors significantly associated with depression. Early screening of depression and treating depression as a routine component of diabetes care are recommended. Further research with a large sample size, wider geographical coverage, and segregation of type of diabetes mellitus is recommended. PMID- 27274297 TI - An indirect comparison of HbA1c treatment effect with albiglutide and exenatide 2.0 mg QW using the Bucher method. AB - No head-to-head comparisons exist between once-weekly (QW) glucagon-like peptide 1 receptor agonists; accordingly, this indirect comparison was conducted to evaluate the comparative efficacy of QW albiglutide vs QW exenatide. Following a systematic literature search, it was determined that HARMONY 7 and DURATION 6, Phase III trials for albiglutide and exenatide, respectively, were similar in study design and baseline characteristics and included a common comparator arm, making them suitable for an indirect comparison using the Bucher method. The primary endpoint of change from baseline in glycated hemoglobin (HbA1c) with albiglutide 50 mg QW and exenatide 2.0 mg QW was compared and tested for noninferiority. The indirect comparison showed a treatment difference of 0.0% (95% confidence interval: -0.189% to 0.189%) in mean change in HbA1c from baseline, and albiglutide 50 mg was noninferior to exenatide 2.0 mg QW at the noninferiority margin of 0.3%. In the absence of a head-to-head trial, these results can be used in pharmacoeconomic analysis and to inform health technology assessment and clinical decision making. PMID- 27274295 TI - Sources and implications of NADH/NAD(+) redox imbalance in diabetes and its complications. AB - NAD(+) is a fundamental molecule in metabolism and redox signaling. In diabetes and its complications, the balance between NADH and NAD(+) can be severely perturbed. On one hand, NADH is overproduced due to influx of hyperglycemia to the glycolytic and Krebs cycle pathways and activation of the polyol pathway. On the other hand, NAD(+) can be diminished or depleted by overactivation of poly ADP ribose polymerase that uses NAD(+) as its substrate. Moreover, sirtuins, another class of enzymes that also use NAD(+) as their substrate for catalyzing protein deacetylation reactions, can also affect cellular content of NAD(+). Impairment of NAD(+) regeneration enzymes such as lactate dehydrogenase in erythrocytes and complex I in mitochondria can also contribute to NADH accumulation and NAD(+) deficiency. The consequence of NADH/NAD(+) redox imbalance is initially reductive stress that eventually leads to oxidative stress and oxidative damage to macromolecules, including DNA, lipids, and proteins. Accordingly, redox imbalance-triggered oxidative damage has been thought to be a major factor contributing to the development of diabetes and its complications. Future studies on restoring NADH/NAD(+) redox balance could provide further insights into design of novel antidiabetic strategies. PMID- 27274298 TI - A qualitative study of perceptions of determinants of disease burden among young patients with type 1 diabetes and their parents in South India. AB - BACKGROUND: Diabetes is a leading threat to public health in India. A huge prevalence of type 1 diabetes among young patients is documented in literature; India is one of the countries with the highest number of new cases per year (10,900), of which 3-4 million face poverty along with diabetes. OBJECTIVE: The aim of this study was to explore the perceptions of determinants of the disease burden among young patients with type 1 diabetes and their parents. METHODS: In June 2014, perceptions were collected from eleven young patients and five available parents using the critical incident technique. RESULTS: Disease burdens associated with the management of type 1 diabetes can vary significantly according to the different social and economic determinants facing each household. Determinants associated with good practices in the management of childhood type 1 diabetes included socioeconomic status, unawareness of health complications, and beliefs about nutrition. Coping strategies applied via lifestyle changes included monitoring glycemia and regular checkups by diabetologists. A general lack of awareness about type 1 diabetes in Indian society, stigmatization, and limited access and systematic barriers to the delivery of optimal health care were all perceived to be factors hindering the successful management of chronic type 1 diabetes by young patients and their parents. CONCLUSION: Stigmatization, a lack of therapeutic adherence, and the financial strains placed on families, particularly on poor ones, are critical. More emphasis must be put on the prevention of acute and long-term complications and education. PMID- 27274299 TI - Enhanced effect of fibroblast growth factor-2-containing dalteparin/protamine nanoparticles on hair growth. AB - PURPOSE: Although treatments for alopecia are in high demand, not all treatments are safe and reliable. Dalteparin/protamine nanoparticles (D/P NPs) can effectively carry growth factors (GFs) such as fibroblast GF (FGF)-2. The purpose of this study was to identify the effects of FGF-2-containing D/P NPs (FGF-2&D/P NPs) on hair growth. PATIENTS AND METHODS: In this study, the participants were 12 volunteers with thin hair. One milliliter of FGF-2 (100 ng/mL) and D/P NPs (56 MUg/mL) was applied and massaged on the skin of the scalp by the participants twice a day. They were evaluated for 6 months. Participants were photographed using a digital camera for general observation and a hair diagnosis system for measuring hair diameter. RESULTS: The mean diameter of the hairs was significantly higher following the application of FGF-2&D/P NPs for 6 months. Objective improvements in thin hair were observed in two cases. Nine participants experienced greater bounce and hair resilience. CONCLUSION: The transdermal application of FGF-2&D/P NPs to the scalp can be used as a new treatment for alopecia. PMID- 27274301 TI - Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach. AB - Ulcerative colitis (UC) is an immune-mediated disease of the colon that is characterized by diffuse and continuous inflammation contiguous from the rectum. Half of UC patients have inflammation limited to the distal colon (proctitis or proctosigmoiditis) that primarily causes symptoms of bloody diarrhea and urgency. Mild-to-moderate distal UC can be effectively treated with topical formulations (rectal suppositories, enemas, or foam) of mesalamine or steroids to reduce mucosal inflammation and alleviate symptoms. Enemas or foam formulations adequately reach up to the splenic flexure, have a minimal side-effect profile, and induce remission alone or in combination with systemic immunosuppressive therapy. Herein, we compare the efficacy, cost, patient tolerance, and side effect profiles of steroid and mesalamine rectal formulations in distal UC. Patients with distal mild-to-moderate UC have a remission rate of approximately 75% (NNT =2) after treatment for 6 weeks with mesalamine enemas. Rectal budesonide foam induces remission in 41.2% of patients with mild-to-moderate active distal UC compared to 24% of patient treated with placebo (NNT =5). However, rectal budesonide has better patient tolerance profile compared to enema formulations. Despite its favorable efficacy, safety, and cost profiles, patients and physicians significantly underuse topical treatments for treating distal colitis. This necessitates improved patient education and physician familiarity regarding the indications, effectiveness, and potential financial and tolerability barriers in using rectal formulations. PMID- 27274300 TI - Recent developments in choledochoscopy: technical and clinical advances. AB - Peroral cholangioscopy has become an important tool in the diagnosis and treatment of a variety of biliary diseases, ranging from indeterminate biliary strictures to bile duct stones. Although the first cholangioscopy was performed in the 1970s, recent technological advances have provided us with cholangioscopes that yield high-resolution images, possess single-operator capability, and have ultrathin design to allow easier maneuverability and detailed imaging of the biliary tract. We review here the currently available devices for peroral cholangioscopy, their clinical applications, limitations, and complications. PMID- 27274302 TI - Impaired bone healing in multitrauma patients is associated with altered leukocyte kinetics after major trauma. AB - Animal studies have shown that the systemic inflammatory response to major injury impairs bone regeneration. It remains unclear whether the systemic immune response contributes to impairment of fracture healing in multitrauma patients. It is well known that systemic inflammatory changes after major trauma affect leukocyte kinetics. We therefore retrospectively compared the cellular composition of peripheral blood during the first 2 weeks after injury between multitrauma patients with normal (n=48) and impaired (n=32) fracture healing of the tibia. The peripheral blood-count curves of leukocytes, neutrophils, monocytes, and thrombocytes differed significantly between patients with normal and impaired fracture healing during the first 2 weeks after trauma (P-values were 0.0122, 0.0083, 0.0204, and <0.0001, respectively). Mean myeloid cell counts were above reference values during the second week after injury. Our data indicate that leukocyte kinetics differ significantly between patients with normal and impaired fracture healing during the first 2 weeks after major injury. This finding suggests that the systemic immune response to major trauma can disturb tissue regeneration. PMID- 27274303 TI - Protective effect of soybean oil- or fish oil-rich diets on allergic airway inflammation. AB - BACKGROUND: The increased prevalence of asthma and allergic diseases in westernized societies has been associated with increased intake of diets rich in n-6 fatty acids (FAs) and poor in n-3 FAs. This study aimed to analyze the prophylactic effects of treatment with a soybean oil-rich diet (rich in n-6) or fish oil (rich in n-3) in an allergic airway inflammation model on lung inflammation score, leukocyte migration, T-helper cell (Th)-2 (interleukin [IL] 4, IL-5) and Th1 (interferon [IFN]-gamma, tumor necrosis factor-alpha) cytokines, lipoxin A4, nitric oxide, bradykinin, and corticosterone levels in bronchoalveolar lavage (BAL) or lungs. METHODS: Male Wistar rats fed with soybean oil- or fish oil-rich diet or standard rat chow were sensitized twice with ovalbumin-alumen and challenged twice with ovalbumin aerosol. The BAL and lungs were examined 24 hours later. RESULTS: Both diets, rich in n-6 or n-3 FAs, impaired the allergic lung inflammation and reduced leukocyte migration, eosinophil and neutrophil percentages, and IL-4/IL-5/bradykinin levels in BAL and/or lungs, as well as increased the nitric oxide levels in BAL. The soybean oil-rich diet additionally increased the levels of lipoxin A4 and corticosterone in the lungs. CONCLUSION: Data presented demonstrated that the n-6 FA-rich diet had protective effect upon allergic airway inflammation and was as anti inflammatory as the n-3 FA-rich diet, although through different mechanisms, suggesting that both diets could be considered as complementary therapy or a prophylactic alternative for allergic airway inflammation. PMID- 27274304 TI - Marfan syndrome: current perspectives. AB - Marfan syndrome (MFS) is a pleiotropic connective tissue disease inherited as an autosomal dominant trait, due to mutations in the FBN1 gene encoding fibrillin 1. It is an important protein of the extracellular matrix that contributes to the final structure of a microfibril. Few cases displaying an autosomal recessive transmission are reported in the world. The FBN1 gene, which is made of 66 exons, is located on chromosome 15q21.1. This review, after an introduction on the clinical manifestations that leads to the diagnosis of MFS, focuses on cardiovascular manifestations, pharmacological and surgical therapies of thoracic aortic aneurysm and/or dissection (TAAD), mechanisms underlying the progression of aneurysm or of acute dissection, and biomarkers associated with progression of TAADs. A Dutch group compared treatment with losartan, an angiotensin II receptor 1 blocker, vs no other additional treatment (COMPARE clinical trial). They observed that losartan reduces the aortic dilatation rate in patients with Marfan syndrome. Later on, they also reported that losartan exerts a beneficial effect on patients with Marfan syndrome carrying an FBN1 mutation that causes haploinsufficiency (quantitative mutation), while it has no significant effect on patients displaying dominant negative (qualitative) mutations. Moreover, a French group in a 3-year trial compared the administration of losartan vs placebo in patients with Marfan syndrome under treatment with beta-receptor blockers. They observed that losartan decreases blood pressure but has no effect on aortic diameter progression. Thus, beta-receptor blockers remain the gold standard therapy in patients with Marfan syndrome. Three potential biochemical markers are mentioned in this review: total homocysteine, serum transforming growth factor beta, and lysyl oxidase. Moreover, markers of oxidative stress measured in plasma, previously correlated with clinical features of Marfan syndrome, may be explored as potential biomarkers of clinical severity. PMID- 27274305 TI - Genetic variations in the osteopontin promoters T-443C and G-156GG increase carotid intima-media thickness. AB - Carotid intima-media thickness (CIMT) is a clear predictor of atherosclerosis. The increase of CIMT is affected by mutations in the osteopontin (OPN) promoters. The purpose of this study was to examine genetic variations in OPN promoters T 443C and G-156GG, identified in Javanese children with ischemic stroke parents, and to investigate their relationship with the increase of CIMT. A case-control analytic study was performed on 20 case and 12 control samples. Case samples were Javanese children aged between 10 to 21 years with ischemic stroke parents. Control samples were children with healthy parents. Mutations of T-443C and G 156GG were determined by employing polymerase chain reaction. Results of sequencing were analyzed using CLC Main Workbench 6.0. CIMT was defined using ultrasound. Genetic variations of T-443C were identified in six samples. Likewise, genetic variations of G-156GG were identified in six samples. Genetic variations in the OPN promoters T-443C and G-156GG were not potential risk factors in an increase of CIMT (P=0.654 and P=0.654). This study proves that genetic variations could be identified at the points of T-443C and G-156GG in children with ischemic stroke parents. Although statistically insignificant, the tendency to increase CIMT occurs in children with genetic variations. Children with ischemic stroke parents have thicker CIMT than children of healthy parents. PMID- 27274306 TI - Get the most from your data: a propensity score model comparison on real-life data. AB - PURPOSE: In the past, the propensity score has been in the middle of several discussions in terms of its abilities and limitations. With a comprehensive review and a practical example, this study examines the effect of propensity score analysis of real-life data and introduces a simple and effective clinical approach. MATERIALS AND METHODS: After the authors reviewed current publications, they applied their insights to the data of a nonrandomized clinical trial in bariatric surgery. This study examined weight loss in 173 patients where 127 patients received Roux-en-Y gastric bypass surgery and 46 patients sleeve gastrectomy. Both groups underwent analysis in terms of their covariate distribution using Mann-Whitney U and chi (2) testing. Mean differences within excess weight loss in native data were examined with Student's t-test. Three propensity score models were defined and matching was performed. Covariate distribution and mean differences in excess weight loss were checked with Mann Whitney U and chi (2) testing. RESULTS: Native data implied a significant difference in excess weight loss. The propensity score models did not confirm this difference. All models proved that both surgical procedures were equal, due to their weight-loss induction. Covariate distribution improved after the matching procedure in terms of an equal distribution. CONCLUSION: It seemed that a practical clinical approach with outcome-related covariates as a propensity score base is the ideal midpoint between an equal distribution in covariates and an acceptable loss of data. Nevertheless, propensity score models designed with clinical intent seemed to be absolutely suitable for overcoming heterogeneity in covariate distribution. PMID- 27274307 TI - Effect of pedicle fixation combined with (125)I seed implantation for metastatic thoracolumbar tumors. AB - PURPOSE: The aim of this study was to investigate the clinical efficacy of pedicle fixation combined with (125)I brachytherapy in treating metastatic thoracolumbar tumors. PATIENTS AND METHODS: A retrospective analysis of the clinical data of seven metastatic thoracolumbar tumor patients who received pedicle fixation combined with radioactive (125)I seed implantation brachytherapy in our department between January 2009 and December 2013 was performed. The visual analog scale (VAS) for pain and the Karnofsky performance status (KPS) score before the operation and 1, 6, and 12 months after the operation were observed and recorded. The changes in the scores at each time point were compared. RESULTS: All the patients underwent a successful operation, without any complications during their hospitalization. All the patients received postoperative follow-up, and the duration of follow-up was 15-50 months, with an average of 32.2 months. One pancreatic cancer patient died of liver failure and hypoproteinemia 28 months post surgery. The VAS scores of patients before the operation and 1, 6, and 12 months after the operation were 7.43+/-0.98, 2.71+/ 0.49, 3.00+/-0.82, and 4.29+/-0.98, respectively; the KPS scores were 52.9+/-9.5, 84.3+/-5.3, 75.7+/-5.3, and 72.9+/-4.9, respectively. These results suggest that the VAS score at each time point was significantly decreased compared with that before the operation, while the KPS score was significantly increased compared with that before the operation. Both differences had statistical significance (P<0.05). CONCLUSION: As a therapy for advanced malignant tumors with thoracolumbar metastasis, pedicle fixation combined with (125)I brachytherapy can effectively relieve short-term pain and improve patient's quality of life. PMID- 27274309 TI - Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening. AB - The discoveries and application of prostate-specific antigen (PSA) have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa) patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized gamma-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (~30%). There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1) adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2) improving test performance using doubling time, density, and ratio of free: total PSA; and 3) fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1) examinations of cell proliferation and cell cycle markers in biopsy specimens; 2) independent quantification of Gleason grading; 3) developing ethnicity-specific staging nomograms based on tumor stage, PSA value, and Gleason score; 4) delineation of the natural history; 5) revisiting the significance of the androgen/testosterone hypothesis; and 6) devoting special attention to individuals with a certain genetic predisposition. Finally, considering the uncertainty that exists in medicine, risk communication on PSA-based screening is indeed due. PMID- 27274308 TI - Profile of palbociclib in the treatment of metastatic breast cancer. AB - Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the molecular expression of estrogen receptor (ER), progesterone receptor, and/or human epidermal growth factor receptor 2 (HER2). These receptors represent important therapeutic targets either through monoclonal antibodies or through small-molecule inhibitors directed toward them. However, up to 40% of patients develop either a primary or a secondary resistance to the current treatments. Therefore, there is an urgent need for investigating new targets in order to overcome the resistance and/or enhance the current therapies. Cell cycle is altered in many human cancers, especially in breast cancer. Cyclin-dependent kinases (CDKs), especially CDK4 and CDK6, play a pivotal role in cell cycle progression that makes them potential targets for new promising therapies. CDK inhibition has shown strong antitumor activities, ranging from cytostatic antiproliferative effects to synergistic effects in combination with other antitumor drugs. In order to overcome the drawbacks of the first-generation CDK inhibitors, recently, new CDK inhibitors have emerged that are more selective to CDK4 and CDK6 such as palbociclib, which is the most advanced CDK4/6 inhibitor in trials. In preclinical studies, palbociclib has shown a very promising antitumor activity, especially against ERalpha+ breast cancer subtype. Palbociclib has gained world attention, and US the Food and Drug Administration has accelerated its approval for first-line treatment in combination with letrozole for the first-line systematic treatment of postmenopausal women with ERalpha+/HER2- locally advanced or metastatic breast cancer. In this review, we discuss the potential role of CDK inhibition in breast cancer treatment, and focus on palbociclib progress from preclinical studies to clinical trials with mentioning the most recent ongoing as well as planned Phase II and Phase III trials of palbociclib in advanced breast cancer. PMID- 27274310 TI - Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics. AB - Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9 tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine. PMID- 27274311 TI - Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine. AB - The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that results from the combination of trastuzumab and DM1, a derivative of the antimicrotubule agent maytansine. This molecule has the ability to enhance cytotoxic drug delivery to specifically targeted cells that overexpress HER2, therefore, maximizing efficacy while sparing toxicity. In recent years, T-DM1 has shown to improve outcomes in metastatic HER2-positive breast cancer that is resistant to trastuzumab. In addition, T-DM1 is currently being tested in the neoadjuvant and adjuvant settings to identify patients who may benefit from this therapy. This review focuses on the mechanism of action, early and late-phase clinical trials, and ongoing studies of T-DM1 in HER2-positive breast cancer. PMID- 27274312 TI - Linkage between the Danish National Health Service Prescription Database, the Danish Fetal Medicine Database, and other Danish registries as a tool for the study of drug safety in pregnancy. AB - A linked population-based database is being created in Denmark for research on drug safety during pregnancy. It combines information from the Danish National Health Service Prescription Database (with information on all prescriptions reimbursed in Denmark since 2004), the Danish Fetal Medicine Database, the Danish National Registry of Patients, and the Medical Birth Registry. The new linked database will provide validated information on malformations diagnosed both prenatally and postnatally. The cohort from 2008 to 2014 will comprise 589,000 pregnancies with information on 424,000 pregnancies resulting in live-born children, ~420,000 pregnancies undergoing prenatal ultrasound scans, 65,000 miscarriages, and 92,000 terminations. It will be updated yearly with information on ~80,000 pregnancies. The cohort will enable identification of drug exposures associated with severe malformations, not only based on malformations diagnosed after birth but also including those having led to termination of pregnancy or miscarriage. Such combined data will provide a unique source of information for research on the safety of medications used during pregnancy. PMID- 27274313 TI - Intramural myomas: to treat or not to treat. AB - A debate among gynecologic and reproductive surgeons is whether or not there is a clinical need to treat all intramural myomas. Considerations include myoma size and number, ability to access them, whether or not they compromise the endometrium, and treatment effect on gynecologic, reproductive, and obstetric outcomes. We conducted a detailed study regarding intramural myomas, their prevalence in subject populations, the imaging methods used to detect them, their growth rate, their suspected adverse effects on gynecologic, fertility, and obstetric outcomes, and the effectiveness of various treatment methods. The growing body of evidence reported in the literature supports the need to manage intramural myomas and to treat them appropriately. PMID- 27274314 TI - An unusual case of posterior reversible encephalopathy syndrome in a patient being weaned from intrathecal morphine. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological entity based on clinical signs, including headache, visual abnormalities, and seizures, and radiological abnormalities mostly consisting of vasogenic brain edema predominantly in the posterior parietal-temporal-occipital regions. PRES typically develops in the setting of a significant " systemic process", including preeclampsia, transplantation, infection/sepsis/shock, autoimmune disease, and cancer chemotherapy, in which hypertension often plays an important role. We present a case of PRES in a 63-year-old female patient with an infected intrathecal morphine pump on a cocktail of antibiotics, morphine, clonidine, diazepam, and amitriptyline. It is the first PRES case in a chronic pain patient, which illustrates that PRES can occur in the absence of any of the established risk factors. We hypothesize it may have been caused by antibiotic treatment in our patient. PMID- 27274315 TI - An unusual case of spontaneous Mycobacterium chelonae corneal ulcer in a healthy middle-aged adult. AB - BACKGROUND: To report a rare presentation of culture-positive Mycobacterium chelonae corneal ulcer and its management. FINDINGS: We report a rare case of a patient with a history of chronic pain and blurriness of vision. Examination revealed a chronic nonhealing paracentral corneal ulcer inferiorly at the 5-7 o'clock meridian with anterior chamber reaction unresponsive to routine antibiotic and antifungal medications with Mantoux test positivity in a middle aged nondiabetic patient with no prior history of trauma, ocular surgery, and contact lens usage. Ziehl-Neelsen staining of the nonhealing ulcer revealed acid fast bacilli typical of M. chelonae, with subsequent culture positivity in Lowenstein-Jensen medium. Subsequent treatment with topical fortified amikacin and tobramycin resulted in rapid healing of the corneal ulcer. CONCLUSION: M. chelonae presenting as a chronic nonhealing corneal ulcer spontaneously occurring in a healthy adult with no predisposing factor draws attention towards the need to have a good index of suspicion by performing a Ziehl-Neelsen stain and culture, and subsequent successful management with topical fortified amikacin and tobramycin. PMID- 27274316 TI - ROM Plus((r)): accurate point-of-care detection of ruptured fetal membranes. AB - Accurate and timely diagnosis of rupture of fetal membranes is imperative to inform and guide gestational age-specific interventions to optimize perinatal outcomes and reduce the risk of serious complications, including preterm delivery and infections. The ROM Plus is a rapid, point-of-care, qualitative immunochromatographic diagnostic test that uses a unique monoclonal/polyclonal antibody approach to detect two different proteins found in amniotic fluid at high concentrations: alpha-fetoprotein and insulin-like growth factor binding protein-1. Clinical study results have uniformly demonstrated high diagnostic accuracy and performance characteristics with this point-of-care test that exceeds conventional clinical testing with external laboratory evaluation. The description, indications for use, procedural steps, and laboratory and clinical characterization of this assay are presented in this article. PMID- 27274318 TI - Management of fecal incontinence - focus on a vaginal insert for bowel control. AB - Fecal incontinence, also referred to as accidental bowel leakage, is a debilitating condition that impacts quality of life in a significant number of women. Current treatments for fecal incontinence include behavioral modification, biofeedback, drug therapy, and invasive surgical procedures. However, these treatments have suboptimal efficacy due to patient adherence, variability of presentation across patients, cost, and additional health risks. A vaginal bowel control system (EclipseTM System) was developed to offer a low-risk, effective, and patient-managed approach to treating accidental bowel leakage. The vaginal bowel control system consists of a vaginal insert and user-controlled, pressure regulated pump. Once inflated, the balloon of the vaginal insert is directed posteriorly to occlude the rectum, allowing the woman to immediately regain control of bowel function. This article will introduce the design evolution and feasibility studies of the Eclipse System. In addition, this review will discuss the results from a recent clinical trial that demonstrated the safety and efficacy of the vaginal bowel control system in managing fecal incontinence and other symptoms of bowel dysfunction. PMID- 27274317 TI - The activL((r)) Artificial Disc: a next-generation motion-preserving implant for chronic lumbar discogenic pain. AB - Degeneration of the lumbar intervertebral discs is a leading cause of chronic low back pain in adults. Treatment options for patients with chronic lumbar discogenic pain unresponsive to conservative management include total disc replacement (TDR) or lumbar fusion. Until recently, only two lumbar TDRs had been approved by the US Food and Drug Administration - the Charite Artificial Disc in 2004 and the ProDisc-L Total Disc Replacement in 2006. In June 2015, a next generation lumbar TDR received Food and Drug Administration approval - the activL((r)) Artificial Disc (Aesculap Implant Systems). Compared to previous generation lumbar TDRs, the activL((r)) Artificial Disc incorporates specific design enhancements that result in a more precise anatomical match and allow a range of motion that better mimics the healthy spine. The results of mechanical and clinical studies demonstrate that the activL((r)) Artificial Disc results in improved mechanical and clinical outcomes versus earlier-generation artificial discs and compares favorably to lumbar fusion. The purpose of this report is to describe the activL((r)) Artificial Disc including implant characteristics, intended use, surgical technique, postoperative care, mechanical testing, and clinical experience to date. PMID- 27274319 TI - Development of devices for self-injection: using tribological analysis to optimize injection force. AB - This article describes the use of analytical models and physical measurements to characterize and optimize the tribological behavior of pen injectors for self administration of biopharmaceuticals. One of the main performance attributes of this kind of device is its efficiency in transmitting the external force applied by the user on to the cartridge inside the pen in order to effectuate an injection. This injection force characteristic is heavily influenced by the frictional properties of the polymeric materials employed in the mechanism. Standard friction tests are available for characterizing candidate materials, but they use geometries and conditions far removed from the actual situation inside a pen injector and thus do not always generate relevant data. A new test procedure, allowing the direct measurement of the coefficient of friction between two key parts of a pen injector mechanism using real parts under simulated use conditions, is presented. In addition to the absolute level of friction, the test method provides information on expected evolution of friction over lifetime as well as on expected consistency between individual devices. Paired with an analytical model of the pen mechanism, the frictional data allow the expected overall injection system force efficiency to be estimated. The test method and analytical model are applied to a range of polymer combinations with different kinds of lubrication. It is found that material combinations used without lubrication generally have unsatisfactory performance, that the use of silicone based internal lubricating additives improves performance, and that the best results can be achieved with external silicone-based lubricants. Polytetrafluoroethylene-based internal lubrication and external lubrication are also evaluated but found to provide only limited benefits unless used in combination with silicone. PMID- 27274320 TI - Evaluation of a novel tool for bone graft delivery in minimally invasive transforaminal lumbar interbody fusion. AB - STUDY DESIGN: Disk material removed (DMR) during L4-5 and L5-S1 transforaminal lumbar interbody fusion (T-LIF) surgery was compared to the corresponding bone graft (BG) volumes inserted at the time of fusion. A novel BG delivery tool (BGDT) was used to apply the BG. In order to establish the percentage of DMR during T-LIF, it was compared to DMR during anterior diskectomy (AD). This study was performed prospectively. SUMMARY OF BACKGROUND DATA: Minimal information is available as to the volume of DMR during a T-LIF procedure, and the relationship between DMR and BG delivered is unknown. BG insertion has been empiric and technically challenging. Since the volume of BG applied to the prepared disk space likely impacts the probability of arthrodesis, an investigation is justified. METHODS: A total of 65 patients with pathology at L4-5 and/or L5-S1 necessitating fusion were treated with a minimally invasive T-LIF procedure. DMR was volumetrically measured during disk space preparation. BG material consisting of local autograft, BG extender, and bone marrow aspirate were mixed to form a slurry. BG slurry was injected into the disk space using a novel BGDT and measured volumetrically. An additional 29 patients who were treated with L5-S1 AD were compared to L5-S1 T-LIF DMR to determine the percent of T-LIF DMR relative to AD. RESULTS: DMR volumes averaged 3.6+/-2.2 mL. This represented 34% of the disk space relative to AD. The amount of BG delivered to the disk spaces was 9.3+/-3.2 mL, which is 2.6+/-2.2 times the amount of DMR. The BGDT allowed uncomplicated filling of the disk space in <1 minute. CONCLUSION: The volume of DMR during T-LIF allows for a predictable volume of BG delivery. The BGDT allowed complete filling of the entire prepared disk space. The T-LIF diskectomy debrides 34% of the disk relative to AD. PMID- 27274321 TI - Benign prostatic hyperplasia and new treatment options - a critical appraisal of the UroLift system. AB - The prostatic urethral lift procedure, more commonly known as UroLift, has been designed to improve male lower urinary tract symptoms while avoiding the complications and disadvantages of existing drug and surgical therapies. In particular, UroLift does not damage ejaculatory function or affect orgasmic sensation. It appears an option for men who wish to avoid long-term drug therapy, the side effects of drugs or surgery and who do not need or will not accept traditional surgical treatments. UroLift was introduced following a series of planned studies that led to US Food and Drug Administration approval in September 2013. UroLift has recently been approved by the UK National Institute for Clinical and Health Excellence (September 2015) as effective and safe and cost effective for use in the UK health system. This review describes the device and the procedure and the evidence base that has led to those approvals. PMID- 27274322 TI - Paritaprevir/ritonavir-ombitasvir and dasabuvir, the 3D regimen for the treatment of chronic hepatitis C virus infection: a concise review. AB - The treatment for chronic hepatitis C has been revolutionized with the development of direct-acting antiviral agents. Several regimens have been approved and are currently used in clinical practice, treating a wide range of patient populations infected with hepatitis C. The interferon-free combination of paritaprevir/ritonavir-ombitasvir and dasabuvir (PrOD or the three-drug [3D] regimen) with or without ribavirin is indicated for the treatment of chronic hepatitis C in both treatment-naive and experienced patients infected with genotype 1, including those coinfected with HIV and patients post-liver transplantation. More recently, paritaprevir/ritonavir-ombitasvir (PrO, or 2D regimen) has been approved in hepatitis C virus patients infected with genotype 4. This review will summarize pharmacokinetic and clinical efficacy data for the 3D regimen in an attempt to help the clinicians delineate its place in the ever increasing direct-acting antiviral armamentarium for the treatment of chronic hepatitis C. PMID- 27274323 TI - Low recurrence rate after mini surgery outside the tendon combined with short rehabilitation in patients with midportion Achilles tendinopathy. AB - BACKGROUND: There is a general opinion that a structured and specific rehabilitation is needed after treatment of midportion Achilles tendinopathy to minimize recurrence of the condition. There is sparse knowledge about the recurrence rates in large patient materials after specific treatments for midportion Achilles tendinopathy. AIM: This study aimed to investigate the recurrence rates in a large number of patients with chronic painful midportion Achilles tendinopathy that had been surgically treated with the ultrasound (US) and Doppler (DP)-guided mini-surgical scraping technique. Postoperatively, a relatively simple rehabilitation protocol, including a range of movement exercises and gradually increased walking and biking before allowing free activity, was used. MATERIALS AND METHODS: From a database, information about the recurrence rates after US + DP-guided mini-surgical scraping, performed by a single surgeon on 519 tendons with US + DP-verified chronic painful midportion Achilles tendinopathy, was obtained. RESULTS: Recurrence of painful midportion Achilles tendinopathy was found in 26 of 519 (5%) operated tendons, 13 from women and 13 from men. In 13 tendons, a close by located plantaris tendon was extirpated during the reoperation. CONCLUSION: In this large material on patients treated with US + DP-guided mini-surgical scraping for midportion Achilles tendinopathy, there were few recurrences, although only a simple and nonspecific rehabilitation protocol was used. PMID- 27274324 TI - Airway dysfunction in elite swimmers: prevalence, impact, and challenges. AB - The prevalence of airway dysfunction in elite swimmers is among the highest in elite athletes. The traditional view that swimmers naturally gravitate toward swimming because of preexisting respiratory disorders has been challenged. There is now sufficient evidence that the higher prevalence of bronchial tone disorders in elite swimmers is not the result of a natural selection bias. Rather, the combined effects of repeated chlorine by-product exposure and chronic endurance training can lead to airway dysfunction and atopy. This review will detail the underpinning causes of airway dysfunction observed in elite swimmers. It will also show that airway dysfunction does not prevent success in elite level swimming. Neither does it inhibit lung growth and might be partially reversible when elite swimmers retire from competition. PMID- 27274325 TI - Mindfulness-based cognitive therapy for depression: trends and developments. AB - Mindfulness-based cognitive therapy (MBCT) was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in negative repetitive thoughts. This review provides an overview of current trends in MBCT research, including efficacy and questions regarding the specific effects of MBCT in light of recent comparisons with structurally equivalent control conditions, mechanisms of change, and moderators of treatment outcome. In addition, future directions are discussed, such as challenges with training an adequate number of therapists and disseminating this therapy. PMID- 27274326 TI - Critical role of ethics in clinical management and public health response to the West Africa Ebola epidemic. AB - The devastation caused by the Ebola virus disease (EVD) outbreak in West Africa has brought to the fore a number of important ethical debates about how best to respond to a health crisis. These debates include issues related to prevention and containment, management of the health care workforce, clinical care, and research design, all of which are situated within the overarching moral problem of severe transnational disadvantage, which has very real and specific impacts upon the ability of citizens of EVD-affected countries to respond to a disease outbreak. Ethical issues related to prevention and containment include the appropriateness and scope of quarantine and isolation within and outside affected countries. The possibility of infection in health care workers impelled consideration of whether there is an obligation to provide health services where personal protection equipment is inadequate, alongside the issue of whether the health care workforce should have special access to experimental treatment and care interventions under development. In clinical care, ethical issues include the standards of care owed to people who comply with quarantine and isolation restrictions. Ethical issues in research include appropriate study design related to experimental vaccines and treatment interventions, and the sharing of data and biospecimens between research groups. The compassionate use of experimental drugs intersects both with research ethics and clinical care. The role of developed countries also came under scrutiny, and we concluded that developed countries have an obligation to contribute to the containment of EVD infection by contributing to the strengthening of local health care systems and infrastructure in an effort to provide fair benefits to communities engaged in research, ensuring that affected countries have ready and affordable access to any therapeutic or preventative interventions developed, and supporting affected countries on their way to recovery from the impact of EVD on their social and economic lives. PMID- 27274327 TI - Enhancements to the multiple sleep latency test. AB - INTRODUCTION: The utility of multiple sleep latency tests (MSLTs) is limited to determining sleep onset latency (SOL) and rapid eye movement sleep latency. The odds ratio product (ORP) is a continuous index of sleep depth with values of 0, 1.0, and 2.5 reflecting very deep sleep, light sleep, and full wakefulness, respectively. We determined the time course of sleep depth during MSLT naps expecting that this would enhance the test's clinical utility. METHODS: Thirty MSLTs (150 naps) were performed for excessive somnolence. Patients indicated whether they slept (yes/no) after each nap. SOL was scored by two experienced technologists. Time course of ORP was determined with a commercial system. We determined ORP at SOL (ORPSOL), times ORP decreased <2.0, <1.5, <1.0 and <0.5 during the entire nap duration, and the integral of decrease in ORP over nap duration (DeltaORPINT). RESULTS: SOL occurred almost invariably when ORP was between 1.0 and 2.0. Of 47 naps (21 patients) with SOL <5 minutes, ORP decreased <1.0 (light sleep) in <5 minutes in only 13 naps (nine patients) and <0.5 (deep sleep) in only two naps in one patient. The relation between ORPINT and frequency of sleep perception was well defined, allowing determination of a threshold for sleep perception. This threshold ranged widely (5-50 DeltaORP*epoch). CONCLUSION: As currently identified, SOL reflects transition into a highly unstable state between wakefulness and sleep. Reporting the times of attaining different sleep depths may help better identify patients at high risk of vigilance loss. Furthermore, an ORPSOL outside the range 1.0-2.0 can help identify scoring errors. PMID- 27274328 TI - Understanding and optimizing health-related quality of life and physical functional capacity in idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive pulmonary disease characterized by the insidious onset of shortness of breath due to parenchymal scarring. As IPF progresses, breathlessness worsens, physical functional capacity declines, and health-related quality of life (HRQL) - the impact of health or disease on a person's satisfaction with their overall station in life - deteriorates. These two inextricably linked variables - breathlessness and physical functional capacity - are strong drivers of HRQL. With the emergence of new and prospective therapies for IPF, it is more important than ever to be able to accurately and reliably assess how IPF patients feel and function. Doing so will promote the development of novel interventions to target impairments in these areas and ensure that the field is capable of assessing the effect of therapeutics interventions on these critically important patient-centered outcomes. PMID- 27274329 TI - Eye Care Quality and Accessibility Improvement in the Community (EQUALITY): impact of an eye health education program on patient knowledge about glaucoma and attitudes about eye care. AB - PURPOSE: To assess the impact of the education program of the Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) telemedicine program on at-risk patients' knowledge about glaucoma and attitudes about eye care as well as to assess patient satisfaction with EQUALITY. PATIENTS AND METHODS: New or existing patients presenting for a comprehensive eye exam (CEE) at one of two retail-based primary eye clinics were enrolled based on >=1 of the following at risk criteria for glaucoma: African Americans >=40 years of age, Whites >=50 years of age, diabetes, family history of glaucoma, and/or preexisting diagnosis of glaucoma. A total of 651 patients were enrolled. A questionnaire was administered prior to the patients' CEE and prior to the patients receiving any of the evidence-based eye health education program; a follow-up questionnaire was administered 2-4 weeks later by phone. Baseline and follow-up patient responses regarding knowledge about glaucoma and attitudes about eye care were compared using McNemar's test. Logistic regression models were used to assess the association of patient-level characteristics with improvement in knowledge and attitudes. Overall patient satisfaction was summarized. RESULTS: At follow-up, all patient responses in the knowledge and attitude domains significantly improved from baseline (P<=0.01 for all questions). Those who were unemployed (odds ratio =0.63, 95% confidence interval =0.42-0.95, P=0.026) or had lower education (odds ratio =0.55, 95% confidence interval =0.29-1.02, P=0.058) were less likely to improve their knowledge after adjusting for age, sex, race, and prior glaucoma diagnosis. This association was attenuated after further adjustment for other patient-level characteristics. Ninety-eight percent (n=501) of patients reported being likely to have a CEE within the next 2 years, whereas 63% (n=326) had a CEE in the previous 2 years. Patient satisfaction with EQUALITY was high (99%). CONCLUSION: Improved knowledge about glaucoma and a high intent to pursue eye care may lead to improved detection of early disease, thus lowering the risk of blindness. PMID- 27274331 TI - A comparison of teaching three common ear, nose, and throat conditions to medical students through video podcasts and written handouts: a pilot study. AB - BACKGROUND: This pilot study conducted at the Peninsula Medical School is one of very few studies to compare the use of video podcasts to traditional learning resources for medical students. METHODS: We developed written handouts and video podcasts for three common ear, nose, and throat conditions; epistaxis, otitis media, and tonsillitis. Forty-one second-year students were recruited via email. Students completed a 60-item true or false statement test written by the senior author (20 questions per subject). Students were subsequently randomized to podcast or handouts. Students were able to access their resource via their unique university login on the university homepage and were given 3 weeks to use their resource. They then completed the same 60-item test. RESULTS: Both podcasts and handouts demonstrated a statistically significant increase in student scores (podcasts mean increase in scores 4.7, P=0.004, 95% confidence interval =0.07). Handout mean increase in scores 5.3, P=0.015, 95% confidence interval =0.11). However, there was no significant difference (P=0.07) between the two, with the handout group scoring fractionally higher (podcasts average post-exposure score =37.3 vs handout 37.8) with a larger average improvement. A 5-point Likert scale questionnaire demonstrated that medical students enjoy using reusable learning objects such as podcasts and feel that they should be used more in their curriculum. CONCLUSION: Podcasts are as good as traditional handouts in teaching second-year medical students three core ear, nose, and throat conditions and enhance their learning experience. PMID- 27274330 TI - Strategies to encourage physical activity in patients with hemophilia to improve quality of life. AB - Hemophilia is a bleeding disorder caused by a congenital abnormality of blood coagulation. Until the mid-1970s, patients with hemophilia (PWH) were advised to refrain from physical activity (PA) because of a perceived increased risk of bleeding. Since then, PA, which is recognized as being essential for health maintenance, is now recommended by the World Federation of Hemophilia. Moreover, a number of studies reported that PA can improve treatment efficacy and prevent bleeding in PWH. Physical assessment and intervention in PA are currently used in clinical practice. However, the necessity of PA is not emphasized, and many PWH generally have low- to- no PA. Therefore, a behavior change approach to encourage patient motivation is becoming ever more important. In this article, we review articles addressing PA in PWH and discuss strategies to encourage PA through a behavior change approach by focusing on factors relevant to hemophilia, such as benefits and bleeding risk of PA, risk management of bleeding, PA characteristics, and difficulty with exercise adherence. The trust relationship between clinicians and patients, a transtheoretical model of behavior change, and motivation theory as approaches to promote PA are introduced. Finally, we review a case report of the clinical success of a behavior change approach to promote PA. Many PWH find it difficult to continue PA because of aging, fear of bleeding, insufficient recognition of PA benefits, and psychological problems. Therefore, it is essential and important to perform prophylaxis with PWH and to heighten their understanding of the benefits and risks of PA, before initiating the exercise regimen. For those patients who find it difficult to participate in PA, it is necessary to plan individual-based behavior change approach and encourage self-efficacy. PMID- 27274332 TI - Physician and medical student perceptions and expectations of the pediatric clerkship: a Qatar experience. AB - BACKGROUND: The average number of clerkship weeks required for the pediatric core rotation by the US medical schools is significantly lower than those required for internal medicine or general surgery. OBJECTIVE: The objective behind conducting this survey study was to explore the perceptions and expectations of medical students and pediatric physicians about the third-year pediatric clerkship. METHODS: An anonymous survey questionnaire was distributed to all general pediatric physicians at Hamad Medical Corporation and to students from Weill Cornell Medical College-Qatar. RESULTS: Feedback was obtained from seven attending pediatricians (100% response rate), eight academic pediatric fellow physicians (100% response rate), 36 pediatric resident physicians (60% response rate), and 36 medical students (60% response rate). Qualitative and quantitative data values were expressed as frequencies along with percentages and mean +/- standard deviation and median and range. A P-value <0.05 from a 2-tailed t-test was considered to be statistically significant. Participants from both sides agreed that medical students receive <4 hours per week of teaching, clinical rounds is the best environment for teaching, adequate bedside is provided, and that there is no adequate time for both groups to get acquainted to each other. On the other hand, respondents disagreed on the following topics: almost two thirds of medical students perceive postgraduate year 1 and 2 pediatric residents as the best teachers, compared to 29.4% of physicians; 3 weeks of inpatient pediatric clerkship is enough for learning; the inpatient pediatric environment is safe and friendly; adequate feedback is provided by physicians to students; medical students have accessibility to physicians; students are encouraged to practice evidence-based medicine; and students get adequate exposure to multi professional teams. CONCLUSION: Assigning devoted physicians for education, providing proper job description or definition of the roles of medical student and physician in the pediatric team, providing more consistent feedback, and extending the duration of the pediatric clerkship can diminish the gap of perceptions and expectations between pediatric physicians and medical students. PMID- 27274333 TI - Systematic review and meta-analysis of Internet interventions for smoking cessation among adults. AB - BACKGROUND: The aim of this systematic review was to determine the effectiveness of Internet interventions in promoting smoking cessation among adult tobacco users relative to other forms of intervention recommended in treatment guidelines. METHODS: This review followed Cochrane Collaboration guidelines for systematic reviews. Combinations of "Internet," "web-based," and "smoking cessation intervention" and related keywords were used in both automated and manual searches. We included randomized trials published from January 1990 through to April 2015. A modified version of the Cochrane risk of bias assessment tool was used. We calculated risk ratios (RRs) for each study. Meta-analysis was conducted using random-effects method to pool RRs. Presentation of results follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. RESULTS: Forty randomized trials involving 98,530 participants were included. Most trials had a low risk of bias in most domains. Pooled results comparing Internet interventions to assessment-only/waitlist control were significant (RR 1.60, 95% confidence interval [CI] 1.15-2.21, I (2)=51.7%; four studies). Pooled results of largely static Internet interventions compared to print materials were not significant (RR 0.83, 95% CI 0.63-1.10, I (2)=0%; two studies), whereas comparisons of interactive Internet interventions to print materials were significant (RR 2.10, 95% CI 1.25-3.52, I (2)=41.6%; two studies). No significant effects were observed in pooled results of Internet interventions compared to face-to-face counseling (RR 1.35, 95% CI 0.97-1.87, I (2)=0%; four studies) or to telephone counseling (RR 0.95, 95% CI 0.79-1.13, I (2)=0%; two studies). The majority of trials compared different Internet interventions; pooled results from 15 such trials (24 comparisons) found a significant effect in favor of experimental Internet interventions (RR 1.16, 95% CI 1.03-1.31, I (2)=76.7%). CONCLUSION: Internet interventions are superior to other broad reach cessation interventions (ie, print materials), equivalent to other currently recommended treatment modes (telephone and in-person counseling), and they have an important role to play in the arsenal of tobacco-dependence treatments. PMID- 27274334 TI - Factors associated with high job satisfaction among care workers in Swiss nursing homes - a cross sectional survey study. AB - BACKGROUND: While the relationship between nurses' job satisfaction and their work in hospital environments is well known, it remains unclear, which factors are most influential in the nursing home setting. The purpose of this study was to describe job satisfaction among care workers in Swiss nursing homes and to examine its associations with work environment factors, work stressors, and health issues. METHODS: This cross-sectional study used data from a representative national sample of 162 Swiss nursing homes including 4,145 care workers from all educational levels (registered nurses, licensed practical nurses, nursing assistants and aides). Care worker-reported job satisfaction was measured with a single item. Explanatory variables were assessed with established scales, as e.g. the Practice Environment Scale - Nursing Work Index. Generalized Estimating Equation (GEE) models were used to examine factors related to job satisfaction. RESULTS: Overall, 36.2 % of respondents reported high satisfaction with their workplace, while another 50.4 % were rather satisfied. Factors significantly associated with high job satisfaction were supportive leadership (OR = 3.76), better teamwork and resident safety climate (OR = 2.60), a resonant nursing home administrator (OR = 2.30), adequate staffing resources (OR = 1.40), fewer workplace conflicts (OR = .61), less sense of depletion after work (OR = .88), and fewer physical health problems (OR = .91). CONCLUSIONS: The quality of nursing home leadership-at both the unit supervisor and the executive administrator level-was strongly associated with care workers' job satisfaction. Therefore, recruitment strategies addressing specific profiles for nursing home leaders are needed, followed by ongoing leadership training. Future studies should examine the effects of interventions designed to improve nursing home leadership and work environments on outcomes both for care staff and for residents. PMID- 27274335 TI - Mothers' willingness to pay for HPV vaccines in Anambra state, Nigeria: a cross sectional contingent valuation study. AB - BACKGROUND: Human papilloma virus (HPV) vaccination in Nigeria will require substantial financing due to high cost of HPV vaccine and inexistence of structures to support adolescent vaccination. Alternative sources are needed to sustain the government funded HPV vaccination programme. This study assessed Nigerian mothers' willingness-to-pay (WTP) for HPV vaccine. We also compared the difference between the average WTP and estimated costs of vaccinating a pre adolescent girl (CVG). METHODS: We conducted a quantitative, cross-sectional, survey-based study in which 50 questionnaires were distributed to each of 10 secondary schools located in two rural and one urban city in Anambra state. The questionnaires were then randomly distributed to girls aged 9-12 years of age to give to their mothers. Contingent valuation approach using the payment card technique was used to estimate the average maximum WTP among the survey participants. Correlates of WTP for HPV vaccination were obtained using multivariate logistic regression. Estimated CVG was obtained by adapting cost of HPV vaccine delivery in Tanzania to the Nigerian setting. RESULTS: A total of 438 questionnaires (88 %) were returned. The average WTP was US$ 11.68. This is opposed to estimated delivery cost of US$ 18.16 and US$ 19.26 for urban and rural populations respectively at vaccine price offered by the Vaccine Alliance (Gavi) and US$ 35.16 and US$ 36.26 for urban and rural populations respectively at the lowest obtainable public sector vaccine price. Demand for HPV vaccine was deemed high (91.6 %) and was significantly associated with respondents previously diagnosed of HPV infection. CONCLUSION: Demand for HPV vaccine was high although short of estimated CVG. High demand for vaccine should be capitalized upon to increase vaccine uptake. Education on cervical cancer and provider-initiated vaccination should be promoted to increase vaccine uptake. Co-payment could be a feasible financing strategy in the event of national HPV vaccination. PMID- 27274336 TI - Relationship between salivary stress biomarker levels and cigarette smoking in healthy young adults: an exploratory analysis. AB - BACKGROUND: This study investigated the relationships among salivary stress biomarkers, cigarette smoking, and mood states. METHODS: The study population comprised 49 healthy sixth-year dental students at Fukuoka Dental College (39 men, 10 women; age, 23-31 years). Lifetime exposure to smoking was calculated using the Brinkman index (BI). Resting saliva samples were collected, and concentrations of cortisol, secretory immunoglobulin A (SIgA), interleukin (IL) 1beta, interleukin-6, and tumor necrosis factor (TNF)-alpha were determined. Mood states (tension-anxiety, depression-dejection, anger-hostility, fatigue, confusion, and vigor) over the previous week were assessed using the Profile of Mood States - Brief Japanese Version. RESULTS: Salivary IL-1beta levels were significantly higher in smokers than non-smokers (P = 0.044), regardless of the BI or mood state. A significant positive correlation was evident between the TNF alpha level and the BI (P = 0.036), and the SIgA level was positively correlated with the BI (P = 0.067) but did not reach statistical significance. In terms of mood states, higher fatigue scores and lower vigor scores were observed in smokers. The TNF-alpha level and vigor score were negatively correlated (r = 0.229, P = 0.135), but the correlation did not reach statistical significance. However, the SIgA level and fatigue score were significantly positively correlated (r = 0.410, P = 0.005). CONCLUSIONS: The TNF-alpha and SIgA levels were both positively correlated with the BI. Furthermore, the TNF-alpha level was negatively correlated with the vigor score, whereas the SIgA level was positively correlated with the fatigue score. Thus, salivary levels of TNF-alpha and SIgA may be used as biomarkers of mood states in healthy young smokers. PMID- 27274337 TI - Prevalent Practices of Thyroid Diseases During Pregnancy Among Endocrinologists, Internists and General Practitioners. AB - BACKGROUND: Maternal thyroid disease in pregnancy is associated with adverse impact on both mother and fetus. Both the American thyroid association and the endocrine society have recently published guidelines for the management of thyroid disease in pregnancy. OBJECTIVES: The objective of this survey was to assess and compare the current practices of various East-Asian physicians in the screening and management of thyroid disease in pregnancy. MATERIALS AND METHODS: Completed survey questionnaires were collected from 112 physicians of six East Asian countries. The survey was based on clinical case scenarios, asking questions about the clinical practices related to diagnosis and management of thyroid disease during pregnancy. Reponses from 76 endocrinologists and 33 internists and general practitioners (generalists) were analyzed. RESULTS: There were minor differences in treatment preferences for Graves' disease in pregnancy and tests to monitor antithyroid drugs between endocrinologists and generalists; the major difference being targeted free thyroxin, and also thyroxin, depicted in the upper end of normal range, by the majority of endocrinologist and within the normal range, by generalists. Compared to generalists, endocrinologists perform more targeted screening and are more familiar with its risk factors. Predominantly, endocrinologists increase levothyroxine dose in hypothyroid women, upon confirmation of pregnancy and also indicate full dose in a pregnant woman, diagnosed with overt hypothyroidism, and treat thyroid peroxidase antibody positive or negative pregnant women with thyroid stimulating hormone (2.5 - 5 mU/L), as compared to generalists. CONCLUSIONS: There is wide variation in the clinical practices of screening and management of thyroid disorders during pregnancy in East-Asia, with many clinicians, in particular general practitioners, not adhering to clinical practice guidelines, unfortunately. PMID- 27274338 TI - Epithelial expression of keratinocytes growth factor in oral precancer lesions. AB - BACKGROUND: Keratinocyte growth factor (KGF) is a potent epithelial mitogen that acts by binding the KGF receptors (KGFRs) expressed on epithelial cells and regulates proliferation and differentiation. The objective of this study was to investigate the expression of KGF in the epithelium in oral precancer. MATERIALS AND METHODS: Archival tissues of oral submucous fibrosis (SMF) and leukoplakia were assessed for epithelial KGF expression by immunohistochemistry and real-time quantitative polymerase chain reaction. RESULTS: KGF was predominantly expressed in the basal and parabasal cells in the epithelium of SMF tissues. KGF transcript in the epithelial cells increased with increasing severity of epithelial dysplasia in oral leukoplakia. CONCLUSION: Although widely reported as a product secreted by the mesenchymal cells, our data suggest that the KGF is also expressed in oral epithelial cells much like the expression in ovarian epithelial cells. Based on the localization of KGF in cells at the epithelial mesenchymal junction and that of the reported presence of KGFR in oral keratinocytes, a potential mechanism involving paracrine and autocrine interactions of KGF and KGFR in early stages of oral precancer is postulated. PMID- 27274339 TI - Association between serotonin transporter gene polymorphism and recurrent aphthous stomatitis. AB - BACKGROUND: Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. MATERIALS AND METHODS: This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. RESULTS: The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. CONCLUSION: Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene. PMID- 27274341 TI - Diagnostic efficacy of color Doppler ultrasound in evaluation of cervical lymphadenopathy. AB - BACKGROUND: To evaluate the efficacy of color Doppler ultrasound (CDUS) in differentiating benign and malignant cervical lymph nodes by detecting differences in blood flow patterns. MATERIALS AND METHODS: In this cross sectional prospective study, 25 untreated patients with clinical evidence of cervical lymphadenopathy were evaluated. CDUS was performed for 80 cervical lymph nodes. The gray scale parameters of the lymph node and intranodal perfusion sites were the key CDUS features used to differentiate between reactive and metastatic lymph nodes. Histopathological confirmations were obtained and compared with the results of CDUS. RESULTS: Initially, 53 cervical lymph nodes were evaluated by clinical examination. Twenty-seven additional lymph nodes (53 + 27 = 80) were discovered by CDUS evaluation. Gray scale parameters for lymph nodes such as size of lymph node, shape of lymph node, and presence or absence of hilum revealed highly significant results (P < 0.0001). Color Doppler flow signals revealed that central/hilar flow was characteristic for benign nodes whereas peripheral/mixed flow was characteristic for malignant nodes, the findings were highly significant (P < 0.0001). Gray scale and color Doppler features are used to differentiate benign and malignant nodes. CONCLUSION: Within the limitations of this study, CDUS evaluation was found to be highly significant with a high sensitivity and specificity over clinical evaluation CDUS examination provides a prospect to reduce the need for biopsy/fine needle aspiration cytology in reactive nodes. PMID- 27274340 TI - Masticatory ability with depression, anxiety, and stress: Does there exist any association? AB - BACKGROUND: Masticatory ability as a subjective response to masticatory function indicates patients' perception of their mastication. To the best of our knowledge, there has been no study on association between masticatory ability and psychological status. This study investigated the association between self assessed masticatory ability (SAMA) and psychological status among a large sample of Iranian adults. MATERIALS AND METHODS: In this cross-sectional study, data were extracted from 4135 adults who had been completed information in 20 counties across Isfahan province regarding masticatory ability and psychological statuses (depression, anxiety, and stress). An SAMA questionnaire, the Hospital Anxiety and Depression Scale and General Health Questionnaire were used to measure masticatory ability, depression and anxiety, and stress of study population. To analyze the data, ANOVA, chi(2) test, and multinomial regression were applied at 0.05 for the significance level. RESULTS: Masticatory ability was significantly correlated with depression (P < 0.001), anxiety (P < 0.001), and stress (P < 0.001). The participants in high masticatory ability group reported lower scores for presence of these psychological variables. Furthermore, males reported significantly higher level for masticatory ability than females (P = 0.025). In addition, there were significant association between low and moderate masticatory ability with anxiety (1.09, 1.08), depression (1.15, 1.13), and stress (1.11, 1.09), respectively. The association was still significant after adjusting for age, sex, educational level, and marital status. CONCLUSION: Despite study limitations, the results of this study provide evidence that participants with higher score of depression, anxiety, and stress suffer lower masticatory ability. PMID- 27274342 TI - Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: A sciatic nerve transection model. AB - BACKGROUND: Effects of platelet-derived growth factor B (PDGF-B) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. MATERIALS AND METHODS: Forty-five male, white Wistar rats were divided into three experimental groups (n = 15), randomly: Normal control group (NC), silicon group (SIL), and PDGF-B treated group (SIL/PDGF). In NC group, left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the SIL group, the left sciatic nerve was exposed in the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone conduit and filled with 10 MUL phosphate buffered solution. In SIL/PDGF group, the silicon conduit was filled with 10 MUL PDGF-B (0.5 ng/mL). Each group was subdivided into three subgroups of five and were studied in 4, 8, 12 weeks after surgery. RESULTS: Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass, and histomorphometric studies showed earlier regeneration of axons in SIL/PDGF than in SIL group (P < 0.05). CONCLUSION: Local administration of PDGF-B combined with silicon grafting could accelerate functional recovery and may have clinical implications for the surgical management of patients after facial nerve transection. PMID- 27274343 TI - A finite element study of teeth restored with post and core: Effect of design, material, and ferrule. AB - BACKGROUND: Different postdesigns and materials are available; however, no consensus exists regarding superiority for stress distribution. The aim of this study was to evaluate the effect of design and material of post with or without ferrule on stress distribution using finite element analysis. MATERIALS AND METHODS: A total of 12 three-dimensional (3D) axisymmetric models of postretained central incisors were made: Six with ferrule design and six without it. Three of these six models had tapered posts, and three had parallel posts. The materials tested were titanium post with a composite resin core, nickel chromium cast post and core, and fiber reinforced composite (FRC) post with a composite resin core. The stress analysis was done using ANSYS software. The load of 100 N at an angle of 45? was applied 2 mm cervical to incisal edge on the palatal surface and results were analyzed using 3D von Mises criteria. RESULTS: The highest amount of stress was in the cervical region. Overall, the stress in the tapered postsystem was more than the parallel one. FRC post and composite resin core recorded minimal stresses within the post but the stresses transmitted to cervical dentin were more as compared to other systems. Minimal stresses in cervical dentine were observed where the remaining coronal dentin was strengthen by ferrule. CONCLUSION: A rigid material with high modulus of elasticity for post and core system creates most uniform stress distribution pattern. Ferrule provides uniform distribution of stresses and decreases the cervical stresses. PMID- 27274344 TI - Marginal adaptation of Spinell InCeram and feldspathic porcelain laminate veneers. AB - BACKGROUND: This in vitro study investigated the marginal fit of two porcelain laminate veneers to help the selection of more accurate veneers in discolored teeth. MATERIALS AND METHODS: Thirty impressions of metal master die created from the prepared labial surface of an acrylic maxillary central incisor were made and poured with Type IV stone. The dies were distributed into test groups (n = 15) for the construction of DuCeram and InCeram laminate veneers. An image-analysis program was used to measure the gap between the veneers and the master die at the labial, lingual, and proximal margins. Statistical analysis was performed with repeated measures ANOVA. Independent t-test was used to compare the mean values between the two groups. Values of P < 0.05 were judged to be significant. RESULTS: Differences between marginal fit of two groups were significant (P < 0.001). The overall mean marginal gap values (MUm) for InCeram and DuCeram were, respectively, 114.4 +/- 40.81 and 282.3 +/- 82.82. Independent t-test revealed significant differences between the marginal gaps of two materials at different predetermined points. CONCLUSION: Within the limitations of this study, the marginal gap in InCeram laminate veneer was within the clinically acceptable standard set at 120 MUm. PMID- 27274345 TI - Evaluation of threshold response and appropriate electrode placement site for electric pulp testing in fluorosed anterior teeth: An in vivo study. AB - BACKGROUND: Accurate diagnosis is key to success. Diagnosing the pulpal status in varied clinical situations poses a challenge to the clinician. Electric pulp test (EPT) is one of the valuable attempts in evaluating the sensibility of pulp tissue. The aim of this study was to find out and compare the threshold levels and optimal electrode placement site for EPT in fluorosed and nonfluorosed anterior teeth. MATERIALS AND METHODOLOGY: Eighty volunteers recruited for this study were divided into two groups based on the incidence of dental fluorosis. Electric pulp testing was done on either of the central incisors in fluorosed and nonfluorosed group. Four sites on each crown were tested 4 times with digitest electric pulp tester, and the mean of the threshold responses was recorded. The data were analyzed with SPSS, version 11. Means of variables from each location were compared using one-way ANOVA and Tukey's post-hoc test while the critical level of significance was set at P < 0.05. RESULTS: The mean and standard deviation of threshold levels in fluorosed teeth were greater when compared to that of nonfluorosed teeth at all sites with incisal edge showing the least mean threshold levels for both the groups (P > 0.05). CONCLUSION: Within the limitations of this study, it can be concluded that fluorosed teeth respond to higher threshold levels than the non-fluorosed teeth, and incisal edge was the optimal electrode placement site. PMID- 27274346 TI - The association between periodontal disease parameters and severity of atherosclerosis. AB - BACKGROUND: Atherosclerosis is the most common cause for heart attack and stroke. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. The aim of this research was to determine the possible association between chronic periodontal disease and severity of atherosclerosis. MATERIALS AND METHODS: Eighty-two subjects that were referred to Chamran Heart Hospital in Isfahan for angiography were involved in this study. Fifty-nine subjects had coronary artery obstruction (CAO) and 23 showed no obstruction after angiography. The severity of CAO was assessed. Periodontal parameters including pocket depth (PD), gingival recession (R), clinical attachment level (CAL), and bleeding on probing (BOP) of all subjects were recorded. The decayed-missing-filled (DMF) index of all subjects was also measured. For statistical analysis, Pearson correlation test, Chi-square, and independent t-test were used. RESULTS: There were significant positive correlation between variables R, PD, CAL, decayed (D), missing (M), DMF, BOP, and degree of CAO. However, there were no significant differences between filling variable degree of CAO (left anterior descending, left circumflex, and right coronary artery). Independent t-test showed that the mean of variables R, PD, AL, D, M, and DMF in patients with obstructed arteries were significantly higher than subjects without CAO. But there were no significant differences between variable F in two groups. CONCLUSION: The results of this cross-section analytical study showed an association between periodontal disease and dental parameters with the severity of CAO measured by angiography. However, this association must not interpret as a cause and effect relationship. PMID- 27274348 TI - Effect of cyclic loading on microleakage of silorane based composite compared with low shrinkage methacrylate-based composites. AB - BACKGROUND: There are many concerns regarding the marginal seal of composite restorations, especially when composite restorations are subjected to cyclic loading. The aim of this study was to evaluate the effect of cyclic loading on the microleakage of silorane based composite compared with low shrinkage methacrylate-based composites in class V cavities. MATERIALS AND METHODS: In this in vitro study, class V cavities were prepared on the facial and lingual surfaces of 48 human premolars (96 cavities). The teeth were randomly divided into four groups of 12 teeth (24 cavities) each and restored as follows: Group 1 (Siloran System Adhesive + Filtek P90), Group 2 (All Bond SE + Aelite LS Posterior), Group 3 (Futurabond NR + Grandio), and Group 4 (G-Bond + Kalore-GC). All the specimens were thermocycled for 2000 cycles (5-55 degrees C) and then half of the specimens from each group, were Load cycled. All teeth were immersed in 0.5% basic fuchsine dye, sectioned, and observed under a stereomicroscope. Data were analyzed using Wilcoxon test, Kruskal-Wallis, and Mann-Whitney U-tests. P < 0.05 was considered as significant. RESULTS: In both unloaded and loaded groups, no statistically significant differences were observed among four composites at the occlusal margin, but a significant difference in gingival microleakage was found between Aelite and silorane. Occlusal and gingival microleakage was not affected by cyclic loading in none of the four restorative materials. CONCLUSION: Silorane did not provide better marginal seal than the low shrinkage methacrylate-based composites (except Aelite). In addition, cyclic loading did not affect the marginal microleakage of evaluated composite restorations. PMID- 27274347 TI - The role of vascular endothelial growth factor in proliferation of odontogenic cysts and tumors: An immunohistochemical study. AB - BACKGROUND: Vascular endothelial growth factor (VEGF) is capable of initiating angiogenesis in blood vessels and may act as mitogenic agent for epithelium of odontogenic cysts and tumors. This study was conducted to evaluate the role of epithelial VEGF expression in odontogenic cysts and ameloblastoma and its correlation with argyrophilic nucleolar organizer region counts to assess its role in their biological behavior. MATERIALS AND METHODS: In this retrospective cross-sectional study, 45 histologically confirmed cases, 15 cases of each of keratocystic odontogenic tumors (KCOTs), dentigerous cysts, and ameloblastomas were examined for immunohistochemical expression for epithelial VEGF, and argyrophilic nucleolar organizer regions (AgNORs) (used as secondary marker in this study) staining was done for comparing the proliferative capacity with VEGF. RESULTS: KCOT shows mild expression within the basal layers and strong expression in the suprabasal layer whereas, in dentigerous cysts, a majority showed no VEGF expression whereas ameloblastomas showed strong expression in all cases by stellate reticulum-like cells at the center of the follicles and suprabasal layers of epithelium. The results of AgNOR counts were higher in KCOTs as compared to ameloblastoma and least in dentigerous cysts. CONCLUSION: VEGF expression by the epithelium of odontogenic cysts and tumors may play a role in epithelial proliferation via autocrine mechanism as reflected by increased AgNOR counts. The angiogenic activity via paracrine pathway may be responsible for the difference in growth rate and neoplastic behavior of the lesions. PMID- 27274349 TI - Children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia: A randomized controlled trial. AB - BACKGROUND: Topical anesthesia has been widely advocated as an important component of atraumatic administration of intraoral local anesthesia. The aim of this study was to use direct observation of children's behavioral pain reactions during local anesthetic injection using cotton-roll vibration method compared with routine topical anesthesia. MATERIALS AND METHODS: Forty-eight children participated in this randomized controlled clinical trial. They received two separate inferior alveolar nerve block or primary maxillary molar infiltration injections on contralateral sides of the jaws by both cotton-roll vibration (a combination of topical anesthesia gel, cotton roll, and vibration for physical distraction) and control (routine topical anesthesia) methods. Behavioral pain reactions of children were measured according to the author-developed face, head, foot, hand, trunk, and cry (FHFHTC) scale, resulting in total scores between 0 and 18. RESULTS: The total scores on the FHFHTC scale ranged between 0-5 and 0-10 in the cotton-roll vibration and control methods, respectively. The mean +/- standard deviation values of total scores on FHFHTC scale were lower in the cotton-roll vibration method (1.21 +/- 1.38) than in control method (2.44 +/- 2.18), and this was statistically significant (P < 0.001). CONCLUSION: It may be concluded that the cotton-roll vibration method can be more helpful than the routine topical anesthesia in reducing behavioral pain reactions in children during local anesthesia administration. PMID- 27274350 TI - Comparison of patients' age receiving therapeutic services in a cleft care team in Isfahan. AB - BACKGROUND: Due to numerous difficulties in patients suffering from varieties of cleft lip and palate, their therapeutic management involves interdisciplinary teamwork. This study was conducted to compare the age of commencing treatments such as speech therapy, secondary palate and alveolar bone grafting and orthodontics between those who sought treatment early and late. MATERIALS AND METHODS: In this retrospective study, 260 files of patients with cleft lip and palate based on their age at the time of admission to a cleft care team were divided into two groups: The early admission and late admission. Both groups compared based on four variables including the mean age of beginning speech therapy, palatal secondary surgery, alveolar bone grafting, and receiving orthodontics using t-test. RESULTS: Based on the results, among 134 patients admitted for speech therapy, the mean age of initiating speech therapy in early clients was 3.3 years, and in the late ones was 9 years. Among 47 patients with secondary surgery, the mean age in early clients was 3.88 years, and in the late clients was 15.7 years. Among 17 patients with alveolar bone grafting, the mean age in the first group was 9 years, and in the other was 16.69 years. Among 24 patients receiving orthodontic services, the mean age in early clients was 7.66 years, and in the second group was 17.05 years. CONCLUSION: There was a significant difference between the age of performing secondary surgery and alveolar bone grafting and the age of beginning speech therapy and receiving orthodontic services in early references and late references to the team. PMID- 27274351 TI - Clinical and radiographic assessment of mineral trioxide aggregate and calcium hydroxide as apexification agents in traumatized young permanent anterior teeth: A comparative study. AB - BACKGROUND: To evaluate and compare the efficacy of mineral trioxide aggregate (MTA) and traditionally used calcium hydroxide (Ca(OH)2) in inducing root end formation of immature roots of traumatized young permanent anterior teeth. MATERIALS AND METHODS: The study was carried out on 22 nonvital, immature permanent maxillary incisors. Samples were allotted into two groups - Group I MTA and Group II Ca(OH)2 Success rate was determined based upon the time duration required for apical barrier formation. The canals were obturated using gutta percha points in MTA group, after 24 h, whereas in Ca(OH)2 group, obturation was carried out after radiographic confirmation of the apical barrier. The clinical and radiographic evaluation was carried out at a follow-up periods of 3, 6, and 9 months and statistical analysis was carried out by SPSS version 15.0 statistical analysis software (Chi-square test and fisher exact test). RESULTS: In MTA Group, barrier formation was observed in 90.90% of the patients after 9 months whereas in Ca(OH)2 Group, the same was observed in 81.81%. The mean time required for barrier formation in MTA group was 4.90 months and 5.33 months in Ca(OH)2 group. CONCLUSION: MTA and Ca(OH)2, as medicaments for apexification, were comparable in terms of the evaluation parameters. However, MTA was beneficial in terms of immediate obturation of immature roots with wide open apices. PMID- 27274352 TI - Definitive guiding flange prosthesis: A definitive approach in segmental mandibulectomy defect. AB - Mandibular discontinuity defects following a segmental mandibulectomy defects present a major challenge to the rehabilitation team. With no immediate intervention to rehabilitate the patient, definitive mandibular guidance prostheses with a metal guiding flange and acrylic teeth on the resected side can be used successfully to stabilize the occlusion and correct the deviation. The present case report describes the prosthodontic rehabilitation of a patient with a segmental mandibulectomy using a mandibular prosthesis with a metal guide flange and a maxillary stabilizing metal framework. PMID- 27274354 TI - Plasticity varies with boldness in a weakly-electric fish. AB - BACKGROUND: The expression of animal personality is indicated by patterns of consistency in individual behaviour. Often, the differences exhibited between individuals are consistent across situations. However, between some situations, this can be biased by variable levels of individual plasticity. The interaction between individual plasticity and animal personality can be illustrated by examining situation-sensitive personality traits such as boldness (i.e. risk taking and exploration tendency). For the weakly electric fish Gnathonemus petersii, light condition is a major factor influencing behaviour. Adapted to navigate in low-light conditions, this species chooses to be more active in dark environments where risk from visual predators is lower. However, G. petersii also exhibit individual differences in their degree of behavioural change from light to dark. The present study, therefore, aims to examine if an increase of motivation to explore in the safety of the dark, not only affects mean levels of boldness, but also the variation between individuals, as a result of differences in individual plasticity. RESULTS: Boldness was consistent between a novel-object and a novel-environment situation in bright light. However, no consistency in boldness was noted between a bright (risky) and a dark (safe) novel environment. Furthermore, there was a negative association between boldness and the degree of change across novel environments, with shier individuals exhibiting greater behavioural plasticity. CONCLUSIONS: This study highlights that individual plasticity can vary with personality. In addition, the effect of light suggests that variation in boldness is situation specific. Finally, there appears to be a trade-off between personality and individual plasticity with shy but plastic individuals minimizing costs when perceiving risk and bold but stable individuals consistently maximizing rewards, which can be maladaptive. PMID- 27274353 TI - Prevalence of Hepatitis C Virus Genotypes Among Patients in Countries of the Eastern Mediterranean Regional Office of WHO (EMRO): A Systematic Review and Meta Analysis. AB - CONTEXT: Hepatitis C virus (HCV) infection is a major global public health issue. The Eastern Mediterranean regional office (EMRO) of the world health organization (WHO) seems to have one of the highest prevalence rates worldwide, with at least 21.3 million HCV-infected patients. OBJECTIVES: The aim of the present study was to review systematically all epidemiological data related to the prevalence of HCV genotypes in infected patients in EMRO countries. DATA SOURCES: A systematic search was conducted of peer-reviewed journals indexed in electronic databases (PubMed, Scopus, ISI, PakMediNet, and IMEMR, and Persian-specific databases including SID, Iran Medex, and MagIran). STUDY SELECTION: A systematic search was performed with temporal limits (papers published between January 2000 up to June 2015), regarding the prevalence and distribution of HCV genotypes in EMRO countries. DATA EXTRACTION: The prevalence rates of HCV genotypes were pooled by metan command in Stata 14. Statistical heterogeneity was explored using the I square at the 5% significance level. Publication bias was assessed, graphically and statistically, by funnel plot and Begg and Egger tests. RESULTS: A total of 563 records were identified through the electronic search. Of these records, 134 studies comprising 67681 HCV-infected individuals were included in the meta analysis. In Iran, subtype 1a was the predominant subtype with a rate of 42% (95% CI, 39 - 46), followed by subtype 3a, 35% (95% CI, 31 - 38). In Pakistan, Subtype 3a was the most common subtype with a rate of 56% (95% CI, 49 - 62), followed by subtype 3b, 10% (95% CI, 7 - 12). In Saudi Arabia and Egypt, genotype 4 was the most prevalent genotype with a rate of 65% (95% CI, 59 - 72) and 69% (95% CI, 36 100) respectively. In Tunisia and Morocco, subtype 1b was the most common subtype with a rate of 69% (95% CI, 50 - 88) and 32% (95% CI, 7 - 56) respectively. CONCLUSIONS: The genotype distribution of HCV takes diverse patterns in EMRO countries. Genotypes 1 and 3 were predominant in Iran and Pakistan, while genotype 4 and 1 were the most common genotypes in the Middle East Arab countries and North African Arab countries. Understanding the genotypes of HCV can help policy makers in designing good strategies for treatment. PMID- 27274355 TI - Suicide surveillance and health systems in Nepal: a qualitative and social network analysis. AB - BACKGROUND: Despite increasing recognition of the high burden of suicide deaths in low- and middle-income countries, there is wide variability in the type and quality of data collected and reported for suspected suicide deaths. Suicide data are filtered through reporting systems shaped by social, cultural, legal, and medical institutions. Lack of systematic reporting may underestimate public health needs or contribute to misallocation of resources to groups most at risk. METHODS: The goal of this study was to explore how institutional structures, cultural perspectives on suicide, and perceived criminality of self-harm influence the type and quality of suicide statistics, using Nepal as an example because of its purported high rate of suicide in the public health literature. Official documentation and reporting networks drawn by police, policy makers, and health officials were analyzed. Thirty-six stakeholders involved in various levels of the death reporting systems in Nepal participated in in-depth interviews and an innovative drawn surveillance system elicitation task. RESULTS: Content analysis and social network analysis revealed large variation across the participants perceived networks, where some networks were linear pathways dominated by a single institution (police or community) with few nodes involved in data transmission, while others were complex and communicative. Network analysis demonstrated that police institutions controlled the majority of suicide information collection and reporting, whereas health and community institutions were only peripherally involved. Both health workers and policy makers reported that legal codes criminalizing suicide impaired documentation, reporting, and care provision. However, legal professionals and law review revealed that attempting suicide is not a crime punishable by incarceration. Another limitation of current reporting was the lack of attention to male suicide. CONCLUSIONS: Establishment and implementation of national suicide prevention strategies will not be possible without reliable statistics and comprehensive standardized reporting practices. The case of Nepal points to the need for collaborative reporting and accountability shared between law enforcement, administrative, and health sectors. Awareness of legal codes among health workers, in particular dispelling myths of suicide's illegality, is crucial to improve mental health services and reporting practices. PMID- 27274356 TI - A xylose-stimulated xylanase-xylose binding protein chimera created by random nonhomologous recombination. AB - BACKGROUND: Saccharification of lignocellulosic material by xylanases and other glycoside hydrolases is generally conducted at high concentrations of the final reaction products, which frequently inhibit the enzymes used in the saccharification process. Using a random nonhomologous recombination strategy, we have fused the GH11 xylanase from Bacillus subtilis (XynA) with the xylose binding protein from Escherichia coli (XBP) to produce an enzyme that is allosterically stimulated by xylose. RESULTS: The pT7T3GFP_XBP plasmid containing the XBP coding sequence was randomly linearized with DNase I, and ligated with the XynA coding sequence to create a random XynA-XBP insertion library, which was used to transform E. coli strain JW3538-1 lacking the XBP gene. Screening for active XBP was based on the expression of GFP from the pT7T3GFP_XBP plasmid under the control of a xylose inducible promoter. In the presence of xylose, cells harboring a functional XBP domain in the fusion protein (XBP+) showed increased GFP fluorescence and were selected using FACS. The XBP+ cells were further screened for xylanase activity by halo formation around xylanase producing colonies (XynA+) on LB-agar-xylan media after staining with Congo red. The xylanase activity ratio with xylose/without xylose in supernatants from the XBP+/XynA+ clones was measured against remazol brilliant blue xylan. A clone showing an activity ratio higher than 1.3 was selected where the XynA was inserted after the asparagine 271 in the XBP, and this chimera was denominated as XynA-XBP271. The XynA-XBP271 was more stable than XynA at 55 degrees C, and in the presence of xylose the catalytic efficiency was ~3-fold greater than the parental xylanase. Molecular dynamics simulations predicted the formation of an extended protein-protein interface with coupled movements between the XynA and XBP domains. In the XynA-XBP271 with xylose bound to the XBP domain, the mobility of a beta-loop in the XynA domain results in an increased access to the active site, and may explain the observed allosteric activation. CONCLUSIONS: The approach presented here provides an important advance for the engineering enzymes that are stimulated by the final product. PMID- 27274357 TI - Lignocellulose-derived thin stillage composition and efficient biological treatment with a high-rate hybrid anaerobic bioreactor system. AB - BACKGROUND: This study aims to chemically characterize thin stillage derived from lignocellulosic biomass distillation residues in terms of organic strength, nutrient, and mineral content. The feasibility of performing anaerobic digestion on these stillages at mesophilic (40 degrees C) and thermophilic (55 degrees C) temperatures to produce methane was demonstrated. The microbial communities involved were further characterized. RESULTS: Energy and sugar cane stillage have a high chemical oxygen demand (COD of 43 and 30 g/L, respectively) and low pH (pH 4.3). Furthermore, the acetate concentration in sugar cane stillage was high (45 mM) but was not detected in energy cane stillage. There was also a high amount of lactate in both types of stillage (35-37 mM). The amount of sugars was 200 times higher in energy cane stillage compared to sugar cane stillage. Although there was a high concentration of sulfate (18 and 23 mM in sugar and energy cane stillage, respectively), both thin stillages were efficiently digested anaerobically with high COD removal under mesophilic and thermophilic temperature conditions and with an organic loading rate of 15-21 g COD/L/d. The methane production rate was 0.2 L/g COD, with a methane percentage of 60 and 64, and 92 and 94 % soluble COD removed, respectively, by the mesophilic and thermophilic reactors. Although both treatment processes were equally efficient, there were different microbial communities involved possibly arising from the differences in the composition of energy cane and sugar cane stillage. There was more acetic acid in sugar cane stillage which may have promoted the occurrence of aceticlastic methanogens to perform a direct conversion of acetate to methane in reactors treating sugar cane stillage. CONCLUSIONS: Results showed that thin stillage contains easily degradable compounds suitable for anaerobic digestion and that hybrid reactors can efficiently convert thin stillage to methane under mesophilic and thermophilic conditions. Furthermore, we found that optimal conditions for biological treatment of thin stillage were similar for both mesophilic and thermophilic reactors. Bar-coded pyrosequencing of the 16S rRNA gene identified different microbial communities in mesophilic and thermophilic reactors and these differences in the microbial communities could be linked to the composition of the thin stillage. PMID- 27274358 TI - If the shoe fits: development of an on-line tool to aid practitioner/patient discussions about 'healthy footwear'. AB - BACKGROUND: A previous study highlighted the importance of footwear to individuals' sense of their identity, demonstrating that shoes must 'fit' someone socially, as well as functionally. However, unhealthy shoes can have a detrimental effect on both foot health and mobility. This project utilises qualitative social science methods to enable podiatrists to understand the broader contribution of footwear to patients' sense of themselves and from this an online toolkit was developed to aid footwear education. METHOD: Semi structured interviews were conducted with six podiatrists/shoe-fitters and 13 people with foot pathologies, some of whom also completed shoe diaries. These were supplemented with some follow-up interviews and photographs of participants' own shoes were taken to allow in-depth discussions. RESULTS: Four areas related to 'fit' were identified; practicalities, personal, purpose and pressures, all of which need to be considered when discussing changes in footwear. These were incorporated into an online toolkit which was further validated by service users and practitioners in a focus group. CONCLUSION: This toolkit can support podiatrists in partnership with patients to identify and address possible barriers to changing footwear towards a more suitable shoe. Enabling patients to make healthier shoe choices will help contribute to improvements in their foot health and mobility. PMID- 27274359 TI - Calcium binding protects E-cadherin from cleavage by Helicobacter pylori HtrA. AB - BACKGROUND: The cell adhesion and tumor suppressor protein E-cadherin is an important factor in the establishment and maintenance of epithelial integrity. E cadherin is a single transmembrane protein, which consists of an intracellular domain (IC), a transmembrane domain (TD), and five extracellular domains (EC). EC domains form homophilic interactions in cis and trans that require calcium binding to the linker region between the EC domains. In our previous studies, we identified the serine protease high temperature requirement A (HtrA) from the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) as a bacterial E-cadherin-cleaving protease that targets the linker region of the EC domains, thereby disrupting gastric epithelial integrity. However, it remains unclear how calcium binding to the E-cadherin linker regions affects HtrA mediated cleavage. RESULTS: Investigating the influence of calcium on the HtrA mediated cleavage of recombinant E-cadherin (rCdh1) in vitro, we tested different concentrations of calcium ions and the calcium chelator ethylenediaminetetraacetic acid (EDTA). Calcium efficiently reduced HtrA-mediated E-cadherin fragmentation. Conversely, the addition of EDTA strongly increased cleavage, resulting in a ladder of defined E-cadherin fragments. However, calcium ions did not affect HtrA oligomerization and protease activity as monitored by degradation of the universal protease substrate casein. Finally, addition of ethyleneglycol-bis-tetraacetic acid (EGTA) slightly enhanced E-cadherin cleavage during H. pylori infection of gastric epithelial cells. CONCLUSIONS: Our results suggest that calcium blocks HtrA-mediated cleavage by interfering with the accessibility of calcium-binding regions between the individual EC domains, which have been identified as cleavage sites of HtrA. PMID- 27274360 TI - World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Vitamin D. AB - BACKGROUND: The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20-30 % in those with an allergic first-degree relative. Vitamin D is involved in the regulation of the immune system and it may play a role in the development, severity and course of asthma and other allergic diseases. OBJECTIVE: The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations addressing the use of vitamin D in primary prevention of allergic diseases. METHODS: Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of randomized controlled trials and non-randomized studies (NRS), specifically cohort and case-control studies, of vitamin D supplementation for the prevention of allergic diseases. We also reviewed the evidence about values and preferences, and resource requirements (up to January 2015, with an update on January 30, 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. RESULTS: Having reviewed the currently available evidence, the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children. The WAO guideline panel suggest not using vitamin D in pregnant women, breastfeeding mothers, or healthy term infants as a means of preventing the development of allergic diseases. This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel's recommendations are conditional and supported by very low certainty evidence. CONCLUSIONS: WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents, clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy, term infants. PMID- 27274361 TI - Complete genome sequence of Leuconostoc gelidum subsp. gasicomitatum KG16-1, isolated from vacuum-packaged vegetable sausages. AB - Leuconostoc gelidum subsp. gasicomitatum is a predominant lactic acid bacterium (LAB) in spoilage microbial communities of different kinds of modified-atmosphere packaged (MAP) food products. So far, only one genome sequence of a poultry originating type strain of this bacterium (LMG 18811(T)) has been available. In the current study, we present the completely sequenced and functionally annotated genome of strain KG16-1 isolated from a vegetable-based product. In addition, six other vegetable-associated strains were sequenced to study possible "niche" specificity suggested by recent multilocus sequence typing. The genome of strain KG16-1 consisted of one circular chromosome and three plasmids, which together contained 2,035 CDSs. The chromosome carried at least three prophage regions and one of the plasmids encoded a galactan degradation cluster, which might provide a survival advantage in plant-related environments. The genome comparison with LMG 18811(T) and six other vegetable strains suggests no major differences between the meat- and vegetable-associated strains that would explain their "niche" specificity. Finally, the comparison with the genomes of other leuconostocs highlights the distribution of functionally interesting genes across the L. gelidum strains and the genus Leuconostoc. PMID- 27274362 TI - Vibrational analysis on the revised potential energy curve of the low-barrier hydrogen bond in photoactive yellow protein. AB - Photoactive yellow protein (PYP) has a characteristic hydrogen bond (H bond) between p-coumaric acid chromophore and Glu46, whose OH bond length has been observed to be 1.21 A by the neutron diffraction technique [Proc. Natl. Acad. Sci. 106, 440-4]. Although it has been expected that such a drastic elongation of the OH bond could be caused by the quantum effect of the hydrogen nucleus, previous theoretical computations including the nuclear quantum effect have so far underestimated the bond length by more than 0.07 A. To elucidate the origin of the difference, we performed a vibrational analysis of the H bond on potential energy curve with O...O distance of 2.47 A on the equilibrium structure, and that with O...O distance of 2.56 A on the experimental crystal structure. While the vibrationally averaged OH bond length for equilibrium structure was underestimated, the corresponding value for crystal structure was in reasonable agreement with the corresponding experimental values. The elongation of the O...O distance by the quantum mechanical or thermal fluctuation would be indispensable for the formation of a low-barrier hydrogen bond in PYP. PMID- 27274363 TI - Guidelines help us to keep calm when facing a difficult airway. PMID- 27274364 TI - A new therapeutic option for postoperative pain management with oxycodone HCI injection. AB - Fentanyl is the most commonly used opioid analgesic in intravenous patient controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID- 27274365 TI - Avoiding negative reviewer comments: common statistical errors in anesthesia journals. AB - Manuscripts submitted to journals should be understandable even to those who are not experts in a particular field. Moreover, they should use publicly available materials and the results should be verifiable and reproducible. Readers and reviewers will want to check the strengths and weaknesses of the research study design, and ways to make this determination should be clear through proper analysis methods. Studies should be described in detail so as to help readers understand the results. Statistical analysis is one of the key methods by which to do this. The inappropriate application of statistical methods could be misleading to readers and clinicians. While many researchers describe their general research methods in detail, statistical methods tend to be described briefly, with certain omissions or errors or other incorrect aspects. For instance, researchers should describe whether the median or mean was used, whether parametric or nonparametric tests were used, whether the data meet the normality test, whether confounding factors were corrected, and whether stratification or matching methods were used. Statistical analysis regardless of the program should be reported correctly. The results may be less reliable if the statistical assumptions before applying the statistical method are not met. These common errors in statistical methods originate from the researcher's lack of knowledge of statistics and/or from the lack of any statistical consultation. The aim of this work is to help researchers know what is important statistically and how to present it in papers. PMID- 27274366 TI - Effect of neuromuscular blockade reversal by pyridostigmine on spectral entropy values during recovery from desflurane anesthesia: a prospective, randomized, double-blind, controlled trial. AB - BACKGROUND: According to several studies investigating the relationship between muscle activity and electroencephalogram results, reversal of neuromuscular blockade (NMB) may affect depth of anesthesia indices. Therefore, we investigated the effect of pyridostigmine on these indices via spectral entropy. METHODS: Fifty-six patients scheduled for thyroidectomy or parotidectomy were included in this study and randomized into two groups. At the start of skin suturing, the desflurane concentration was adjusted to 4.2 vol% in both groups. Following this, the pyridostigmine group (group P, n = 28) was administered pyridostigmine 0.2 mg/kg mixed with glycopyrrolate 0.04 mg/kg, while the control group (group C, n = 28) received normal saline. Entropy values (response entropy [RE] and state entropy [SE]), train of four (TOF) ratio, and end-tidal desflurane concentration were recorded from point of drug administration to 15 minutes post-drug administration. RESULTS: Mean RE values at 15 minutes, when the maximum effect of pyridostigmine was anticipated, showed a statistically significant difference between groups (53.8 +/- 10.5 in group P and 48.0 +/- 8.8 in group C; P = 0.030). However, mean SE at 15 minutes showed no significant difference between the two groups (P = 0.066). At 15 minutes, there were significant differences in the TOF ratio between the two groups (P < 0.001). CONCLUSIONS: NMB reversal by pyridostigmine significantly increased RE values but not SE values. This finding suggests that spectral entropy may be a useful alternative tool for monitoring anesthetic depth during recovery from anesthesia in the presence of electromyogram activity. PMID- 27274367 TI - Acupressure versus dilution of fentanyl to reduce incidence of fentanyl-induced cough in female cancer patients: a prospective randomized controlled study. AB - BACKGROUND: Fentanyl-induced cough (FIC) is a transient condition with a reported incidence of 18% to 65% depending on the dose and route of administration of fentanyl. Nonpharmacological methods to prevent FIC are more cost-effective than medications. Dilution of fentanyl has a proven role in the prevention of FIC. Acupressure can also prevent FIC because it has a proven role in the treatment of cough. METHODS: This study included 225 female patients with an American Society of Anesthesiologists physical status of I or II who were randomly divided into 3 groups of 75 patients each. Patients in the control group received undiluted fentanyl at 3 ug/kg, patients in the acupressure group received undiluted fentanyl at 3 ug/kg with acupressure, and patients in the dilution group received diluted fentanyl at 3 ug/kg. Coughing was noted within 2 min of fentanyl administration. The severity of FIC was graded as mild (1-2 coughs), moderate (3 4 coughs), or severe (>=5 coughs). The timing of coughs was also noted. RESULTS: The incidence of FIC was 12.7% in the control group, 6.8% in the dilution group, and 1.3% in the acupressure group. The difference in the incidence of cough was statistically significant (P = 0.008) between the control and acupressure groups. The difference in the severity of cough among the groups was not statistically significant. The median onset time of cough among all groups was 9 to 12 seconds. CONCLUSIONS: The application of acupressure prior to administration of fentanyl significantly reduces the incidence of FIC. Dilution of fentanyl also reduces the incidence of FIC, but the difference is not statistically significant. PMID- 27274368 TI - Relationship between first-twitch depression and train-of-four ratio during sugammadex reversal of rocuronium-induced neuromuscular blockade. AB - BACKGROUND: The primary outcome of sugammadex reversal for rocuronium-induced neuromuscular block (NMB) is a train-of-four ratio (TOFR) of 0.9, not first twitch (T1) height. We investigated whether the recovery of TOFR or T1 differs based on the reversal of NMB with neostigmine or sugammadex. METHODS: The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in 80 patients after induction of anesthesia. The TOFR and T1 height were recorded, and saved in a personal computer using TOF-Watch SX Monitor software in all patients. Patients were randomly assigned to 2 groups to receive either neostigmine 50 ug/kg with glycopyrrolate 10 ug/kg (neostigmine group, n = 40) or sugammadex 2.0 mg/kg (sugammadex group, n = 40). The primary objective was to determine the difference of recovery time between TOFR to 0.9 and T1 to 0.9 after sugammadex or neostigmine administration during moderate rocuronium-induced NMB. RESULTS: The recovery pattern of the TOFR 2 min after sugammadex administration was 1.0 or more, but that of T1 was less than 90% (T1 / control value) up to 6 min after drug was injected. The recovery pattern of TOFR and T1 was similar during the 20 min after reversal with neostigmine. CONCLUSIONS: If you have not performed the T1 monitoring, both TOFR and T1 should be considered to confirm suitable recovery during the 6 min after reversal with sugammadex during rocuronium-induced moderate NMB. PMID- 27274369 TI - Encountering unexpected difficult airway: relationship with the intubation difficulty scale. AB - BACKGROUND: An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. METHODS: We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. RESULTS: For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. CONCLUSIONS: Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation. PMID- 27274370 TI - Change of QT variability index during general anesthesia. AB - BACKGROUND: The QT variability index (QTVI)-a non-invasive measure of beat-to beat QT interval (QTI) fluctuations-is related to myocardial repolarization lability. The QTVI represents the relationship between QTI and the RR interval. Elevated QTVI is associated with an increased risk of malignant ventricular arrhythmias and sudden death. We investigated the influence of general anesthesia and tourniquets on the QTVI. METHODS: We studied fifty patients who received total knee replacement arthroplasty under sevoflurane anesthesia. We measured QTI, corrected QTI (QTc), T-wave peak-to-end interval (TPE), QTVI, and heart rate variability. All variables were calculated at baseline (B), 30 min after general anesthesia (A), 30 min (TQ1) and 60 min (TQ2) after tourniquet inflation, and at tourniquet deflation (TQR). RESULTS: Prolongation of QTI was detected at all times, and QTc was significantly prolonged TQR. TPE was unchanged during general anesthesia. The QTVI was significantly decreased and more negative during anesthesia and tourniquet inflation. After deflation of the tourniquet, the QTVI was restored to preanesthetic values. Low frequency (LF) was significantly decreased during general anesthesia, but high frequency (HF) was somewhat maintained, except at TQ2. The LF/HF ratio was significantly decreased at A and TQ2. CONCLUSIONS: Sevoflurane based general anesthesia induced repolarization stability and, more negativity of the QTVI, in patients undergoing total knee replacement arthroplasty. PMID- 27274371 TI - The prophylactic effect of dexamethasone on postoperative sore throat in prone position surgery. AB - BACKGROUND: Sore throat and hoarseness are common complications after general anesthesia with tracheal intubation. The position for patients can affect the incidence of postoperative sore throat (POST) by causing displacement of the endotracheal tube. This study investigated the prophylactic effect of dexamethasone in prone position surgeries. METHODS: One hundred-fifty patients undergoing lumbar spine surgery (18-75 yr) were randomly allocated into the normal saline group (group P, n = 50), dexamethasone 0.1 mg/kg group (group D1, n = 50) or dexamethasone 0.2 mg/kg group (group D2, n = 50). The incidence and severity of POST, hoarseness, and cough were measured using direct interview at 1, 6, and 24 h after tracheal extubation. The severity of POST, hoarseness, and cough were graded using a 4-point scale. RESULTS: At 1, 6, and 24 h after extubation, the incidence of sore throat was significantly lower in group D1 (1 h; P = 0.015, 6 h; P < 0.001, 24 h; P = 0.038) and group D2 (1 h; P < 0.001, 6 h; P < 0.001, 24 h; P = 0.017) compared to group P. There were less number of patients in the groups D1 and D2 than group P suffering from moderate grade of POST at 1, 24 h after extubation. The incidence of hoarseness at 1, 6, and 24 h after extubation was significantly lower in groups D2 than group P (P < 0.001). There were no significant differences in the incidence of cough among the three groups. CONCLUSIONS: The prophylactic use of dexamethasone 0.1 mg/kg and 0.2 mg/kg in prone surgery reduces the incidence of postoperative sore throat and dexamethasone 0.2 mg/kg decreases the incidence of hoarseness. PMID- 27274372 TI - Thiamylal sodium increased inflammation and the proliferation of vascular smooth muscle cells. AB - BACKGROUND: Thiamylal sodium is a common anesthetic barbiturate prepared in alkaline solution for clinical use. There is no previously reported study on the effects of barbiturates on the inflammation and proliferation of vascular smooth muscle cells (VSMCs). Here, we examined the effects of clinical-grade thiamylal sodium solution (TSS) on the inflammation and proliferation of rat VSMCs. METHODS: Expression levels of interleukin (IL)-1alpha, IL-1beta, IL-6, and toll like receptors in rat VSMCs were detected by quantitative reverse transcription polymerase chain reaction and microarray analyses. The production of IL-6 by cultured VSMCs or ex vivo-cultured rat aortic segments was detected in supernatants by enzyme-linked immunosorbent assay. VSMC proliferation and viability were determined by the water-soluble tetrazolium-1 assay and trypan blue staining, respectively. RESULTS: TSS increased expression of IL-1alpha, IL 6, and TLR4 in VSMCs in a dose-dependent manner, and reduced IL-1beta expression. Ex vivo TSS stimulation of rat aorta also increased IL-6. Low concentrations of TSS enhanced VSMC proliferation, while high concentrations reduced both cell proliferation and viability. Expression of IL-1 receptor antagonist, which regulates cell proliferation, was not increased by TSS stimulation. Exposure of cells to the TSS additive, sodium carbonate, resulted in significant upregulation of IL-1alpha and IL-6 mRNA levels, to a greater extent than TSS. CONCLUSIONS: TSS induced proinflammatory cytokine production by VSMCs is caused by sodium carbonate. However, pure thiamylal sodium has an anti-inflammatory effect in VSMCs. TSS exposure to VSMCs may promote vascular inflammation, leading to the progression of atherosclerosis or in-stent restenosis, resulting in vessel bypass graft failure. PMID- 27274374 TI - Anesthetic experience of patient with isolated left ventricular noncompaction: a case report. AB - Isolated left ventricular noncompaction (LVNC) is a rare primary genetic cardiomyopathy characterized by prominent trabeculation of the left ventricular wall and intertrabecular recesses. Perioperative management of the patient with LVNC might be challenging due to the clinical symptoms of heart failure, systemic thromboembolic events, and fatal left ventricular arrhythmias. We conducted real time intraoperative transesophageal echocardiography in a patient with LVNC undergoing general anesthesia for ovarian cystectomy. PMID- 27274373 TI - Experience of hemostasis in tracheal bleeding very close to the carina by the bronchial blocker: a case report. AB - Massive hemoptysis is respiratory compromise which should be managed as a life threatening condition. In our case, the bronchial blocker played a role in hemostasis of tracheal bleeding very close to the carina and prevented further spillage into the contralateral lung. Right-sided one-lung isolation in an 87 year-old female, who received cardiopulmonary resuscitation due to myocardial infarction, was requested due to hemoptysis. Right-sided bronchial bleeding was suspected on auscultation, but esophageal and tracheal bleeding due to violent intubation with a stylet was also considered. We attempted one-lung isolation with the bronchial blocker. The bronchial blocker was inadvertently advanced to the left mainstem bronchus, but the inflated balloon of the bronchial blocker compressed the site of bleeding, which was within 1 cm proximal and left posterior to the carina. Tracheal bleeding stopped, and we confirmed that hemostasis was achieved with the balloon of the bronchial blocker using a fiberoptic bronchoscope. PMID- 27274375 TI - Severe hypoxemia during carinal resection in the lateral position under one-lung ventilation of a non-dependent lung: a case report. AB - During one-lung ventilation (OLV) in the lateral position, the dependent, ventilated lung receives more blood flow than the non-dependent, non-ventilated lung owing to gravity, improving the match of ventilation and perfusion. Conversely, in the rare clinical situations when OLV is applied to the non dependent lung, arterial oxygenation can get worse due to considerable shunt flow to the dependent non-ventilated lung. We report a case of severe hypoxemia during carinal resection under OLV of a non-dependent lung. In this case, OLV had to be applied to the non-dependent lung in the lateral position because the bronchus of the non-dependent lung was anastomosed with the trachea, whereas the bronchus of the dependent lung had already been resected for carinal resection. The subsequent hypoxemia resulting from the shunt flow to the dependent non ventilated lung was treated successfully by ligating the pulmonary artery of the dependent lung. PMID- 27274376 TI - Anesthetic management of patient with Sjogren's syndrome who underwent cesarean section: a case report. AB - Sjogren's syndrome is one of the most common autoimmune disorders and has a female predominance. Maternal circulating autoantibodies such as anti-Ro/SSA and anti-La/SSB antibodies can cause congenital heart block of fetus, and in severe case, emergency pacemaker implantation may be needed for neonate. Therefore, it is very important to understand maternal and fetal condition and pay attention to the status of the neonate during delivery. In this paper, we present a case of patient with Sjogren's syndrome who underwent cesarean section under spinal anesthesia. PMID- 27274377 TI - Emergency cesarean section in an epidemic of the middle east respiratory syndrome: a case report. AB - Only a few reports have been published on women with an infectious respiratory viral pathogen, such as Middle East Respiratory Syndrome (MERS) Coronavirus delivering a baby. A laboratory confirmed case of MERS was reported during a MERS outbreak in the Republic of Korea in a woman at gestational week 35 + 4. She recovered, and delivered a healthy baby by emergency cesarean section (C-sec). We present the clinical course and the emergency C-sec in a pregnant woman with MERS. PMID- 27274378 TI - Cardiac arrest due to intracranial hypotension following pseudohypoxic brain swelling induced by negative suction drainage in a cranioplasty patient: a case report. AB - Pseudohypoxic brain swelling (PHBS) is known to be an uncommon event that may occur during and following an uneventful brain surgery, when negative suction drainage is used. The cerebrospinal fluid loss related to suction drainage can evoke intracranial hypotension that progress to PHBS. The main presentations of PHBS are sudden unexpected circulatory collapses, such as severe bradycardia, hypotension, cardiac arrest, consciousness deterioration and diffuse brain swelling as seen with brain computerized tomography (CT). We present a stuporous 22-year-old patient who underwent cranioplasty under general anesthesia. The entire course of the general anesthesia and operation progressed favorably. However, the time of scalp suture completion, sudden bradycardia and hypotension occurred, followed by cardiac arrest immediately after initiation of subgaleal and epidural suction drainage. After successful resuscitation, the comatose patient was transferred to the neurosurgical intensive care unit and PHBS was confirmed using brain CT. PMID- 27274379 TI - Lethal coronary air embolism caused by the removal of a double-lumen hemodialysis catheter: a case report. AB - Coronary air embolism is a rare event. We report a case in which an acute myocardial infarction occurred in the region supplied by the right coronary artery after the removal of a double-lumen hemodialysis catheter. Emergent coronary angiography revealed air bubbles obstructing the mid-segment of the right coronary artery with slow flow phenomenon distally. The patient expired due to myocardial infarction. PMID- 27274380 TI - Simply modified percutaneous tracheostomy using the Cook(r) Ciaglia Blue RhinoTM: a case series. AB - When first introduced, percutaneous dilatational tracheostomy (PDT) was performed using a bronchoscope. The bronchoscope itself, however, has several disadvantages, including interruption of ventilation. Modifications of the standard PDT technique have suggested that PDT can be safely performed without a bronchoscope. However, the safety of these modifications is unclear and many modifications have yet to be widely adopted. This study retrospectively evaluated the safety of a simplified PDT technique using the Cook(r) Ciaglia Blue RhinoTM in 186 patients. After confirming the underlying structures by palpation, PDT was performed without a bronchoscope or blunt dissection, 2.0 cm below the cricothyroid membrane. Ultrasonography was used only when palpation was difficult. Except for bleeding in three patients with coagulopathy, none of the patients experienced any early or late complications, and there were no deaths related to PDT. These findings confirm that PDT can be safely performed using a simplified technique, which may be useful in situations with limited equipment and medical personnel. PMID- 27274381 TI - Iatrogenic iliac arteriovenous fistula with aortic pseudoaneurysm formation post lumbar (L4-L5) laminectomy and pedicular screw fixation. PMID- 27274382 TI - Erratum: Heart rate variability as a predictor of hypotension after spinal anesthesia in hypertensive patients. AB - [This corrects the article on p. 317 in vol. 65, PMID: 24228144.]. PMID- 27274383 TI - False Replies on Smoking Rate Surveys and an In-Hospital Smoking Cessation Clinic. PMID- 27274385 TI - Compliance and Effectiveness of Smoking Cessation Program Started on Hospitalized Patients. AB - BACKGROUND: Varenicline is now very useful medication for cessation; however, there is only little result of researches with varenicline for cessation of hospitalized patients. This research attempted to analyze the cessation effect of medication and compliance of hospitalized patients. METHODS: This research included data for 52 patients who were prescribed varenicline among 280 patients who were consulted for cessation during their admission period. This research checked whether smoking was stopped or not after six months and analyzed their compliance, the factors for succeeding in smoking cessation. RESULTS: One hundred and ninety hospitalized patients participated in smoking cessation counseling among 280 patients who included consultation from their admission departments. And varenicline was prescribed for only 80 patients after counseling. Nineteen smokers were successful in smoking cessation among 52 final participants representing the rating of success of 36.5%. The linkage between compliance of varenicline and rate of smoking successful has no statistical significance. The factors for succeeding in smoking of hospitalized patients are admission departments, diseases, and economic states. CONCLUSION: Smoking cessation program has low inpatient compliance. Cooperation of each departments is very important for better compliance. Success rate of cessation was relatively high (36.5%). Cessation attempt during hospitalization is very effective strategy. PMID- 27274384 TI - Pharmacotherapy of Acute Bipolar Depression in Adults: An Evidence Based Approach. AB - In the majority of cases of bipolar disorder, manic episodes are usually brief and typically responsive to currently available psychopharmacological agents. In contrast, depressive manifestations are more prevalent and persistent, and can present as major depressive/mixed episodes or residual interepisode symptoms. The depressive phase is often associated with other neuropsychiatric conditions, such as anxiety spectrum disorders, substance use disorders, stressor-related disorders, and eating disorders. It is viewed as a systemic disease with associated ailments such as metabolic syndrome, diabetes mellitus, and cardiovascular disease. There is an increased rate of mortality not only from suicide, but also from concomitant physical illness. This scenario is made worse by the fact that depressive symptoms, which represent the main disease burden, are often refractory to existing psychotropic drugs. As such, there is a pressing need for novel agents that are efficacious in acute depressive exacerbations, and also have applicable value in preventing recurrent episodes. The rationale of the present review is to delineate the pharmacotherapy of the depressive phase of bipolar disorder with medications for which there is evidence in the form of observational, open-label, or double-blind randomized controlled studies. In the treatment of acute bipolar depression in adults, a comprehensive appraisal of the extant literature reveals that among mood stabilizers, the most robust proof of efficacy exists for divalproex sodium; while atypical antipsychotics, which include olanzapine, quetiapine, lurasidone, and cariprazine, are also effective, as demonstrated in controlled trials. PMID- 27274386 TI - Effectiveness of Intraluminal Air Decompression on Postcolonoscopic Pain According to Reinsertion Site. AB - BACKGROUND: Colonoscopy is a very effective and essential examination to diagnose colorectal cancer; however, many patients experience discomfort due to post examination abdominal pain, which reduces colonoscopy compliance. This study was conducted to determine methods for reducing post-colonoscopic abdominal pain. METHODS: We conducted a randomized controlled study of 405 male and female adults who visited Hana General Hospital in Cheongju. We surveyed general characteristics, history of colonoscopy, and other related factors, then categorized examinees into 5 groups (0-5) according to the site of scope reinsertion. Pain was measured using a numeric rating scale (NRS). RESULTS: The mean age of examinees in this study was 47.8 years, and 210 participants had prior experience of colonoscopy. No significant difference was observed between variables, with the exception of reinsertion duration (P=0.005). Pain scores were different between performing physicians (P=0.006), and were higher when the subjective level of procedure difficulty was low (P=0.026) in univariate analysis. Pain scores decreased as the reinsertion site became closer to the proximal colon (P<0.001), but there was no significant difference between groups 3 and 4. The results of multiple logistic regression analysis, including univariate analysis, showed that group 1 had 0.48 times, group 2 had 0.38 times, group 3 had 0.09 times, and group 4 had 0.03 times odds ratio (moderate-to-severe pain, NRS >=4) than control group 0. CONCLUSION: Air decompression by scope reinsertion is an effective way to reduce abdominal pain after colonoscopy. Removing air when the reinserted scope approaches the hepatic flexure seems to be the most effective method to reduce post-colonoscopic pain. PMID- 27274388 TI - Discrepancy between Self-Reported and Urine-Cotinine Verified Smoking Status among Korean Male Adults: Analysis of Health Check-Up Data from a Single Private Hospital. AB - BACKGROUND: Enquiry into smoking status and recommendations for smoking cessation is an essential preventive service. However, there are few studies comparing self reported (SR) and cotinine-verified (CV) smoking statuses, using medical check-up data. The rates of discrepancy and under-reporting are unknown. METHODS: We performed a cross-sectional study using health examination data from Healthcare System Gangnam Center, Seoul National University Hospital in 2013. We analyzed SR and CV smoking statuses and discrepancies between the two in relation to sociodemographic variables. We also attempted to ascertain the factors associated with a discrepant smoking status among current smokers. RESULTS: In the sample of 3,477 men, CV smoking rate was 11.1% higher than the SR rate. About 1 in 3 participants either omitted the smoking questionnaire or gave a false reply. The ratio of CV to SR smoking rates was 1.49 (95% confidence interval [CI], 1.38 1.61). After adjusting for confounding factors, older adults (>=60 years) showed an increased adjusted odds ratio (aOR) for discrepancy between SR and CV when compared to those in their twenties and thirties (aOR, 5.43; 95% CI, 2.69-10.96). Educational levels of high school graduation or lower (aOR, 2.33; 95% CI, 1.36 4.01), repeated health check-ups (aOR, 1.45; 95% CI, 1.03-2.06), and low cotinine levels of <500 ng/mL (aOR, 2.03; 95% CI, 1.33-3.09), were also associated with discordance between SR and CV smoking status. CONCLUSION: Omissions and false responses impede the accurate assessment of smoking status in health check-up participants. In order to improve accuracy, it is suggested that researcher pay attention to participants with greater discrepancy between SR and CV smoking status, and formulate interventions to improve response rates. PMID- 27274387 TI - The Association between Frailty and Cognition in Elderly Women. AB - BACKGROUND: Frailty refers to the loss of physiologic complexity and the associated decline in ability to withstand stressors as one gets older. It is defined as unintentional weight loss, exhaustion, weakness, slow walking speed, and low physical activity. According to several western studies, frailty is associated with cognitive impairment, but there have been few studies about the relationship between frailty and cognitive impairment in Korea. Thus, the purpose of this study is to analyze the relationship between cognition and factors related to frailty such as grip strength, walking speed, physical activity, and depression, among female patients older than 65 in Korea. METHODS: A total of 121 subjects among the outpatients of the department of family medicine at Kangbuk Samsung Hospital who did not meet the exclusion criteria were included in this study. We divided the participants into 2 groups, according to the Korean version of the Montreal Cognitive Assessment (MoCA) score: 1 group with subjects that had normal cognition and the other group with patients that had impaired cognition. A comparison was made between the 2 groups in regards to the factors related to frailty, and we completed equation that predicting cognition from the frailty related factors. RESULTS: Compared with the impaired cognition group, the subjects in the normal cognition group had higher hand strength, and walked faster (P<0.001). There was no statistically significant difference in physical activity between the 2 groups (P=0.19). When multiple linear regression analysis was performed using age, grip strength, and walking speed as the predictor variables and MoCA score as the dependent variable, the regression coefficients were calculated to be: -0.2015, 0.2294, 1.2372, and -0.1436, respectively (P<0.05). CONCLUSION: In Korean female patients who are older than 65 years of age, cognition tends to decline as grip strength decreases, walking speed gets slower, depression becomes more severe, and as age increases. PMID- 27274389 TI - Accuracy of Korean-Mini-Mental Status Examination Based on Seoul Neuro Psychological Screening Battery II Results. AB - BACKGROUND: The Korean-Mini-Mental Status Examination (K-MMSE) is a dementia screening test that can be easily applied in both community and clinical settings. However, in 20% to 30% of cases, the K-MMSE produces a false negative response. This suggests that it is necessary to evaluate the accuracy of K-MMSE as a screening test for dementia, which can be achieved through comparison of K MMSE and Seoul Neuropsychological Screening Battery (SNSB)-II results. METHODS: The study included 713 subjects (male 534, female 179; mean age, 69.3+/-6.9 years). All subjects were assessed using K-MMSE and SNSB-II tests, the results of which were divided into normal and abnormal in 15 percentile standards. RESULTS: The sensitivity of the K-MMSE was 48.7%, with a specificity of 89.9%. The incidence of false positive and negative results totaled 10.1% and 51.2%, respectively. In addition, the positive predictive value of the K-MMSE was 87.1%, while the negative predictive value was 55.6%. The false-negative group showed cognitive impairments in regions of memory and executive function. Subsequently, in the false-positive group, subjects demonstrated reduced performance in memory recall, time orientation, attention, and calculation of K-MMSE items. CONCLUSION: The results obtained in the study suggest that cognitive function might still be impaired even if an individual obtained a normal score on the K-MMSE. If the K MMSE is combined with tests of memory or executive function, the accuracy of dementia diagnosis could be greatly improved. PMID- 27274390 TI - The Association between Taking Dietary Supplements and Healthy Habits among Korean Adults: Results from the Fifth Korea National Health and Nutritional Examination Survey (2010-2012). AB - BACKGROUND: Recently, the number of people interested in health in South Korea has increased, and the rate of dietary supplement use is rising. Researchers have hypothesized that the rate of practicing healthy habits is higher among those who use dietary supplements than those who do not. Therefore, this study aimed to discover the association between taking dietary supplements and practicing various healthy habits in the Korean, adult population. METHODS: The sample included 15,789 adults over 19 years old who participated in the fifth Korea National Health and Nutrition Examination Survey. The user group was defined as those taking dietary supplements for more than 2 weeks during the previous year or once during the past month. Measures for the seven healthy habits were based on those included in the Alameda study and were analyzed accounting for the complex sampling design. RESULTS: The rate of taking dietary supplements was significantly higher in women, middle aged participants, urban residents, those with a higher income, those with a higher education level, and nonsmokers as well as among women with a moderate subjective health status, women who limited their alcohol content, and women with dyslipidemia. In the adjusted analysis, the rate of performing three of the 'Alameda 7' habits-eating breakfast regularly, restricting snacking, and limiting drinking-was higher in the female dietary supplement user group than in the other groups. Women practiced more healthy habits and had a higher dietary supplement intake rate than men. CONCLUSION: We found that taking dietary supplements in Korean adults is highly associated with demographic and social factors. Taking dietary supplements had a relationship with dietary habits, and there was no significant association between dietary supplement and other healthy habits. Thus in the health clinic, we suggest that taking dietary supplements complements a patient's healthy habits, with the exception of dietary habits, for health promotion. PMID- 27274391 TI - Comparison of Surrogate Markers as Measures of Uncomplicated Insulin Resistance in Korean Adults. AB - BACKGROUND: Metabolic syndrome (MS) is known to increase the risk of various cardiometabolic diseases and in-sulin resistance (IR) has known to have central role in the development of MS. Many surrogate indices of IR have been proposed and the detection of MS might be a suitable model for assessing the accuracy of surrogate indices. The aims of our study are to invest the most appropriate index by assessment of the diagnostic capacity of IR among each surrogate index and identifying cut-off values for discriminating uncomplicated MS in Korean adults. METHODS: A cross-sectional study was performed, assessing 294 Korean adults, 85 of whom were diagnosed with uncomplicated MS. The sensitivities and specificities of five surrogate IR indices were compared to discriminate MS from healthy subjects; these included fasting serum insulin, homeostasis model assessment insulin resistance index, quantitative insulin sensitivity check index, McAuley index, and Disse index. Correlations between each index value were assessed using Pearson's and Spearman's correlation methods. RESULTS: The McAuley index showed the highest area under the curve (0.85), specificity (86.12%), accuracy (82.31%), positive predictive value (68.13%), and negative predictive value (88.67%) to distinguish MS, with a cut-off point of 5.3 defined. Correlation coefficients of the five indices showed that the McAuley index had the strongest correlation with IR. CONCLUSION: The McAuley index showed the best accuracy in the detection of MS as a surrogate marker of IR. To establish more effective and accurate standards of measuring IR, comprehensive and multi-scaled studies are required. PMID- 27274392 TI - Optic Neuropathy in Thyroid Eye Disease: A Case Series. AB - In patients with thyroid disease, ocular involvement or thyroid ophthalmopathy is common, irrespective of their thyroid status. A common feature of thyroid eye disease is eyelid retraction, which leads to a classical starry gaze (Kocher sign). Treatment with radioactive iodine (RAI) is a known therapy for hyperthyroidism. However, this treatment may lead to or worsen thyroid ophthalmopathy. We report a case series of two patients with thyrotoxicosis, who presented with an atypical and subtle occurrence of thyroid eye disease (TED) soon after RAI therapy. One of the patients was initially diagnosed and treated for dry eyes; however, over a period of time, the patient's vision progressively deteriorated. Clinical and radiological investigations confirmed thyroid ophthalmopathy with low serum thyroid hormone levels. Both patients recovered well after immediate intensive intravenous steroid treatment. These cases highlight the importance of recognizing partial ptosis as one of the presenting signs of active TED among general practitioners and physicians. PMID- 27274393 TI - Targeted antiangiogenic agents in combination with cytotoxic chemotherapy in preclinical and clinical studies in sarcoma. AB - Sarcomas are a heterogeneous group of mesenchymal malignancies. In recent years, studies have demonstrated that inhibition of angiogenic pathways or disruption of established vasculature can attenuate the growth of sarcomas. However, when used as monotherapy in the clinical setting, these targeted antiangiogenic agents have only provided modest survival benefits in some sarcoma subtypes, and have not been efficacious in others. Preclinical and early clinical data suggest that the addition of conventional chemotherapy to antiangiogenic agents may lead to more effective therapies for patients with these tumors. In the current review, the authors summarize the available evidence and possible mechanisms supporting this approach. PMID- 27274394 TI - A smoke-free medical campus in Jerusalem: data for action. AB - BACKGROUND: Establishing smoke-free environments is a major component of tobacco control policy. The introduction of a smoke-free policy in medical campuses may serve as a role model for other educational and health institutions but little has been published about their prevalence or impact. In 2012, the Faculty of Medicine at Hebrew University-Hadassah in Jerusalem, Israel launched a smoke-free Medical Campus initiative. This study examined smoking behaviours, cigarette smoke exposure and attitudes towards the smoke-free campus policy among students and employees. METHODS: Using a self-administered questionnaire, data was collected from medical, dental and pharmacy students, as well as employees of the school of pharmacy. We approached the entire target population in 2013 (N = 449), with a response rate of 72.5 % (N = 313). RESULTS: The rate of smoking was 8.3 % (95 % CI 5.5-11.9 %). Most participants reported daily exposure or exposure several times a week to cigarette smoke (65.8 %). Overall, 98.0 % had reported seeing people smoke in open campus areas and 27.2 % indoors. Most participants supported the smoking ban inside buildings (94.2 %) but fewer supported (40.8 %) a complete ban of smoking throughout the campus, including outside areas. Only 18.4 % agreed that a policy prohibiting smoking was unfair to smokers. A multivariable analysis showed that support for a complete ban on smoking on campus was higher among non-smokers than for smokers (OR = 9.5, 95 % CI 2.2-31.5, p = 0.02). CONCLUSIONS: The smoke-free policy does not have total compliance, despite the strong support among both students and employees for a smoke-free medical campus. The data collected will assist policy makers move towards a total smoke-free medical campus and will aid tobacco control efforts in Israel and other countries. PMID- 27274395 TI - Optimizing dietary lipid use to improve essential fatty acid status and reproductive performance of the modern lactating sow: a review. AB - Dietary lipid supplementation benefits the prolific and high-producing modern lactating sow. A comprehensive review of recent studies showed that lipid supplementation increases average daily energy intake, which is partitioned for lactation as indicated by greater milk fat output and improved litter growth rate. Recent compelling findings showed that addition of particular lipids during lactation improved the subsequent reproductive outcome of sows. Such benefits were related to the level of dietary essential fatty acids (EFA, linoleic acid, C18:2n-6; and alpha-linolenic acid, C18:3n-3) during lactation. Lactation diets without supplemental EFA resulted in a pronounced negative balance (intake minus milk output) of linoleic (-25.49 g/d) and alpha-linolenic acid (-2.75 g/d); which compromised sow fertility (farrowing rate < 75 % and culling rates > 25 % of weaned sows). This phenomenon seems to be increasingly important with advancing sow age because of a progressive reduction of body EFA pool over successive lactations. The net effect of supplemental EFA during lactation was to create a positive EFA balance, which improved the subsequent reproduction of sows. Adequate linoleic acid intake improved the proportion of sows that farrowed in the subsequent cycle (Farrowing rate (%) = [(-1.5 * 10(-3) * linoleic acid intake (g/d)(2)) + (0.53 * linoleic acid intake (g/d)) + (45.2)]; quadratic P = 0.002, R(2) = 0.997, RMSE = 0.031). In addition, increasing linoleic acid intake increased the number of pigs born in the subsequent cycle (total pigs born (n) = [(9.4 * 10(-5) * linoleic acid intake (g/d)(2)) + (0.04 * linoleic acid intake (g/d)) + (10.94)]; quadratic P = 0.002, R(2) = 0.997, RMSE = 0.031). Supplemental alpha-linolenic acid resulted in a rapid return to estrus (sows bred: sows weaned = 94.2 %; wean-to-estrus interval = 4.0 d) and achieved a high retention of pregnancy (sows pregnant: sows bred = 98 %). Collectively, we conclude that a minimum dietary intake of 10 g/d of alpha-linolenic acid, simultaneous with a minimum of 125 g/d of linoleic acid should be provided to >= 95 % of the sows; thereby, achieving a maximum sow reproductive efficiency through multiple mechanisms that include rapid return to estrus, high maintenance of pregnancy and large subsequent litter size in mature sows, that appear to be susceptible to EFA deficiency. PMID- 27274396 TI - The effectiveness of physiotherapy treatment on balance dysfunction and postural instability in persons with Parkinson's disease: a systematic review and meta analysis. AB - BACKGROUND: Balance dysfunction and postural instability in Parkinson's disease are among the most relevant determinants of an impaired quality of life. Physiotherapy interventions are essential to reduce the level of disability by treating balance dysfunction and postural instability. The aim of this systematic review with meta-analysis was to test the effectiveness of conventional physiotherapy interventions in the management of balance dysfunction and postural instability in Persons with idiopathic Parkinson's disease. METHOD: A systematic literature search of the Cochrane Library, PubMed/Medline, PEDro, Rehadat, and Rehab Trials were performed by 2 reviewers (AY and AT) independently. Eligible randomised controlled trials published from September 2005 to June 2015 were included. The selected RCTs, which investigated the effects of conventional physiotherapy treatments in the management of postural instability and balance dysfunction in Persons with Parkinson's disease, were assessed on a methodological quality rating scale. Included studies differed clearly from each other with regard to patient characteristics, intervention protocol, and outcome measures. Important characteristics and outcomes were extracted, summarized and analyzed. RESULTS: Eight trials with a total of 483 participants were eligible for inclusion of which 5 trials provide data for meta-analysis. Benefits from conventional physiotherapy treatment were reported for all of the outcomes assessed. The pooled estimates of effects showed significantly improved berg balance scale (SMD, 0.23; 95 % CI, 0.10-0.36; P < 0.001) after exercise therapy, in comparison with no exercise or sham treatment. Exercise interventions specifically addressing components of balance dysfunction demonstrated the largest efficacy with moderate effect size (SMD, 5.98; 95 % CI, 2.29-9.66; P < 0.001). Little effects were observed for interventions that specifically targeted Falls efficacy scale. The pooled data indicated that physiotherapy exercises decreased the incidence of falling by 6.73 (95 % CI: -14.00, 0.54, p = 0.07) with the overall effect of Z = 1.81. CONCLUSION: Physiotherapy interventions like balance training combined with muscle strengthening, the range of movement and walking training exercise is effective in improving balance in patients with Parkinson's disease and more effective than balance exercises alone. Highly challenging balance training and incremental speed-dependent treadmill training can also be part of a rehabilitation program for management of balance dysfunction and Postural instability in patients with idiopathic Parkinson's disease. PMID- 27274397 TI - A retrospective review of the two-step tuberculin skin test in dialysis patients. AB - BACKGROUND: Reactivation of latent Mycobacterium tuberculosis infection (LTBI) is a health concern for patients on dialysis or receiving a kidney transplant, as these patients are often immunosuppressed. The most frequently used test for LTBI screening in this population is the tuberculin skin test (TST). The diagnostic accuracy (sensitivity and specificity) of the TST in a contemporary North American or Western European dialysis population is unknown. OBJECTIVES: Our objective was to determine the diagnostic accuracy and clinical utility of the two-step TST in patients receiving dialysis. DESIGN: This is a retrospective cohort study. SETTING: This study is set at four tertiary dialysis units across Winnipeg, Manitoba. PATIENTS: There are 483 chronic hemodialysis and peritoneal dialysis patients in the study. MEASUREMENTS: The measurements are sensitivity and specificity of the TST with respect to abnormal chest X-ray. METHODS: All patients received a two-step TST and assessment of risk factors for prior tuberculosis (TB) infection between February 2008 and December 2008. This cohort was retrospectively linked to our tuberculosis registry to ascertain if prophylaxis was received for LTBI. RESULTS: At an induration cutoff of 5 mm, 62 (13 %) patients had a positive two-step TST. Patients with a known Bacillus Calmette-Guerin (BCG) vaccination were more likely to test positive (50 % of those with a positive TST had a BCG versus 34 % with a negative TST, p = 0.05). Using a diagnostic gold standard of an abnormal chest X-ray as a proxy for LTBI, the sensitivity of the TST was only 14 % and the specificity was 88 %. Only 8 of 62 patients with a positive TST (13 %) received prophylaxis for LTBI. None of the patients who tested negative were treated. LIMITATIONS: There is a lack of a truly accurate gold standard for LTBI. CONCLUSIONS: The TST has limited diagnostic and clinical utility for LTBI screening in patients on dialysis. Further research into the diagnostic accuracy of interferon-gamma release assays and a revision of LTBI screening guidelines in patients on dialysis should be considered. PMID- 27274398 TI - Preliminary study for predicting better methotrexate efficacy in Japanese patients with rheumatoid arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammatory status, joint destruction, disability, and pain. Methotrexate (MTX) has been confirmed to reduce disease activity and delay or stabilize the development of bone erosions. However, major drawbacks are that patients show great interindividual variability in response to MTX and the unpredictable occurrence of side effects. A strategy for personalized MTX treatment to predict its efficacy and toxicity has not yet been determined. To establish personalized MTX therapy in Japanese patients with rheumatoid arthritis, we performed a preliminary study for predicting better methotrexate efficacy including single-nucleotide polymorphisms (SNPs) for MTX-related transporters/enzymes. METHODS: Disease control status (good or poor) was judged by the number of Disease Activity Scores (DAS28) of <2 for 6-12 months. The response index R was calculated by the improved area under the curve (AUC) of the DAS28 score for 0-3 or 0-6 months by dividing the cumulative dose of MTX during 0 3 or 0-6 months, respectively. Genotyping of alleles of RFC1 80G > A, RFC1 -43 T > C, FPGS 1994G > A, GGH 401C > T, MTHFR 1298A > C, and TYMS 3'-UTR (-6/+6) was performed using the real-time PCR system. RESULTS: Seven of 21 patients were judged as good responders in terms of disease control, and the remainder as poor responders. For 0-3 months after starting MTX administration, the median cumulative dose and improved DAS28 AUC in the good and poor response groups were 96.0 mg and 25.4 and 118.0 mg and 23.4, respectively. For 0-6 months, the median cumulative dose and improved DAS28 AUC in the good and poor response groups were 192.0 mg and 51.0 and 214.0 mg and 47.6, respectively. Statistically significant differences between the 2 groups in the 0-6-month period were observed in DAS28 AUC improvement and index R. A slight tendency for a correlation between G/G genotypes and A allele genotypes in RFC1 80 genotypes was observed, although it did not reach statistical significance. CONCLUSION: This study suggested that aggressive RA treatment with MTX from the early period of administration is necessary to obtain a good response after 6 months, although no SNPs predicting a better treatment response to MTX were identified. PMID- 27274399 TI - The Effects of Kangaroo Mother Care and Swaddling on Venipuncture Pain in Premature Neonates: A Randomized Clinical Trial. AB - BACKGROUND: Hospitalized premature babies often undergo various painful procedures. Kangaroo mother care (KMC) and swaddling are two pain reduction methods. OBJECTIVES: This study was undertaken to compare the effects of swaddling and KMC on pain during venous sampling in premature neonates. PATIENTS AND METHODS: This study was performed as a randomized clinical trial on 90 premature neonates. The neonates were divided into three groups using a random allocation block. The three groups were group A (swaddling), group B (KMC), and group C (control). In all three groups, the heart rate and arterial oxygen saturation were measured and recorded in time intervals of 30 seconds before, during, and 30, 60, 90, and 120 seconds after blood sampling. The neonate's face was video recorded and assessed using the premature infant pain profile (PIPP) at time intervals of 30 seconds. The data was analyzed using the t-test, chi-square test, Repeated Measure analysis of variance (ANOVA), Kruskal-Wallis, Post-hoc, and Bonferroni test. RESULTS: The findings revealed that pain was reduced to a great extent in the swaddling and KMC methods compared to the control group. However, there was no significant difference between KMC and swaddling (P >= 0.05). CONCLUSIONS: The results of this study indicate that there is no meaningful difference between swaddling and KMC on physiological indexes and pain in neonates. Therefore, the swaddling method may be a good substitute for KMC. PMID- 27274400 TI - Intracranial subdural empyema after surgery for lumbar lipomyelomeningocele: A rare complication. AB - BACKGROUND: Surgery is routinely recommended for lumbar lipomyelomeningocele, especially in the setting of tethered cord syndrome. The most common complications are wound infections and cerebrospinal fluid (CSF) leak, which remain confined to the surgical site. To the best of our knowledge, there have been no prior reports relating an intracranial subdural empyema following detethering surgery. Prompt diagnosis is essential since subdural empyema is a neurosurgical emergency. CASE DESCRIPTION: The patient was an 11-month-old male who underwent detethering surgery for a lumbar lipomyelomeningocele. This was followed by wound drainage consistent with CSF leak, requiring revision. Cultures grew three aerobes (Escherichia coli, Enterococcus, and Klebsiella) and three anaerobes (Clostridium, Veillonella, and Bacteroides). He was started on cefepime, vancomycin, and flagyl. The patient required two more wound revisions and placement of an external ventricular drain (EVD) secondary to persistent wound leakage. A subsequent magnetic resonance imaging (MRI) brain was carried out due to protracted irritability, which revealed extensive left subdural empyema along the parietooccipital region and the inferior and anterior temporal lobe. He underwent evacuation of the subdural empyema where cultures exhibited no growth. Subsequently, he progressed well. His lumbar incision continued to heal. Serial MRI brains and inflammatory markers were reassuring. He weaned off his EVD and went home to complete a 6-week course of antibiotics. Upon completion of his antibiotics, he returned for a clinic visit; he exhibited no interim fevers or wound issues; cranial imaging documented no evidence of a residual or recurrent subdural empyema. CONCLUSION: Intracranial subdural empyema may occur after wound complications from detethering surgery despite early initiation of broad-spectrum antibiotics. Possible etiology may be local wound infection that seeds the subdural space and travels to the cranium, leading to meningitis and subdural empyema. Such a scenario should prompt surveillance imaging of the head as undiagnosed subdural empyema may lead to devastating consequences. PMID- 27274401 TI - A rare case of giant multiseptated thoracic myelomeningocele with segmental placode: Commentary. PMID- 27274403 TI - Intracranial extra-axial hemangioma in a newborn: A case report and literature review. AB - BACKGROUND: Congenital hemangiomas are benign vascular tumors, and the intracranial counterpart was described in very few cases. CASE DESCRIPTION: A newborn presented with an intracranial tumor associated with an arachnoid cyst, diagnosed by antenatal ultrasound at 37 weeks of gestation. Surgery was indicated due to increased head circumference and bulging fontanelle, and a complete resection of an extra-axial red-brown tumor was performed at the 3(rd) week of life. Microscopy revealed a hemangioma. CONCLUSION: Hemangioma is a rare differential diagnosis that must be considered in extra-axial intracranial tumors affecting infants and neonates. The radiological features are not helpful in differentiating from other tumors, and surgery is indicated when the diagnosis is uncertain or whenever there are signs of increased intracranial pressure. PMID- 27274402 TI - Hydrocephalus caused by unilateral foramen of Monro obstruction: A review on terminology. AB - BACKGROUND: Hydrocephalus caused by unilateral foramen of Monro (FM) obstruction has been referred to in literature by many different terminologies. Precise terminology describing hydrocephalus confined to just one lateral ventricle has a very important prognostic value and determines whether or not the patient can be shunt free after an endoscopic procedure. METHODS: Aiming to define the best term for unilateral FM obstruction, 19 terms were employed on PubMed database (http://www.ncbi.nlm.nih.gov/pubmed) as quoted phrases. RESULTS: A total of 194 articles were found. Four patterns of hydrocephalus were discriminated as a result of our research term query and were divided by types for didactic purpose. Type A - partial dilation of the lateral ventricle; Type B - pure unilateral obstruction of the FM; Type C - previously shunted patients with secondary obstruction of the FM; and Type D - asymmetric lateral ventricles with patent FM. CONCLUSION: In unilateral FM obstruction hydrocephalus, an in-depth review on terminology application is critical to avoid mistakes that may compromise comparisons among different series. This terminology review suggests that Type B hydrocephalus, i.e., the hydrocephalus confined to just one lateral ventricle with no other sites of cerebrospinal fluid circulation blockage, are best described by the terms unilateral hydrocephalus (UH) and monoventricular hydrocephalus, the first being by far the most popular. Type A hydrocephalus is best represented in the literature by the terms uniloculated hydrocephalus and loculated ventricle; Type C hydrocephalus by the terms isolated lateral ventricle and isolated UH; and Type D hydrocephalus by the term asymmetric hydrocephalus. PMID- 27274404 TI - Pediatric knowledge update: Approach to the management of vein of Galen aneurysmal malformations in neonates. PMID- 27274405 TI - Large solitary osteochondroma of the thoracic spine: Case report and review of the literature. AB - BACKGROUND: Spinal osteochondromas are typically benign tumors, but patients may present with myelopathy and neurologic deficits if there is tumor encroachment within the spinal canal. CASE DESCRIPTION: We report here a case of a large solitary osteochondroma originating from the posterior vertebral body of T9 causing spinal cord compression and myelopathy. A 17-year-old man presented with 3 months of bilateral feet numbness and gait difficulty. Imaging demonstrated a large left-sided 5.9 cm * 5.0 cm * 5.4 cm osseous mass arising from the T9 vertebra consistent with an osteochondroma. He underwent bilateral costotransversectomies, and a left two-level lateral extracavitary approach for three partial corpectomies to both safely decompress the spinal canal as well as obtain a gross total resection of the tumor. Use of the O-arm intraoperative stereotactic computed tomographic navigation system assisted in delineating the osseous portions of the tumor for surgical removal. He experienced complete neurologic recovery after operative intervention. CONCLUSION: Careful surgical planning is needed to determine the best approach for spinal cord decompression and resection of this tumor, especially taking into account the bony elements from which it arises. We present this case, to highlight the feasibility of a single-stage posterior approach to the ventral thoracic spine for the resection of a large solitary thoracic osteochondroma causing cord compression. PMID- 27274406 TI - How to avoid perioperative visual loss following prone spinal surgery. AB - BACKGROUND: In a prior article, "Perioperative visual loss (POVL) following prone spinal surgery: A review," Epstein documented that postoperative visual loss (POVL) occurs in from 0.013% to 0.2% of spine procedures performed in the prone position. POVL is largely attributed to ischemic optic neuropathy (ION), central retinal artery occlusion (CRAO), cortical blindness (CB), direct compression (prone pillows/horseshoe, eye protectors), and rarely, acute angle closure glaucoma. METHODS: Risk factors for ION include prolonged surgery, extensive fusions, anemia, hypotension, hypovolemia, diabetes, obesity, use of the Wilson frame, male sex, and microvascular pathology. CRAO may result from improper prone positioning (e.g., eye compression or rotation contributing to jugular/venous or carotid compression), while CB more typically results from both direct compression and obesity. RESULTS: Several preventive/prophylactic measures should limit the risk of POVL. The routine use of an arterial line and continuous intraoperative monitoring document intraoperative hypotension/hypovolemia/anemia that can be immediately corrected with appropriate resuscitative measures. Application of a 3-pin head holder completely eliminates direct eye compression and maintains the neck in a neutral posture, thus avoiding rotation that can contribute to jugular/venous obstruction and/or inadvertent carotid compression. In addition, elevating the head 10 degrees from the horizontal directly reduces intraocular pressure. CONCLUSIONS: The best way to avoid POVL following prone spine surgery is to prevent it. Routine use of an arterial line, intraoperative monitoring, a 3-pin head holder, and elevation of the head 10 degrees from the horizontal should limit the risk of encountering POVL after spinal procedures performed in the prone position. PMID- 27274407 TI - Low reoperation rate following 336 multilevel lumbar laminectomies with noninstrumented fusions. AB - BACKGROUND: Few reoperations are required in older patients undergoing multilevel lumbar laminectomy with noninstrumented fusions for spinal stenosis with/without spondylolisthesis/instability, and they rarely require instrumentation. METHODS: We reviewed 336 patients averaging 66.5 years of age undergoing initial average 4.7 level lumbar laminectomies with average 1.4 level noninstrumented fusions over an average 7.1-year period (range 2.0-16.5 years). Patients uniformly exhibited spinal stenosis, instability (Grade I [195 patients] or Grade II spondylolisthesis [67 patients]), disc herniations (154 patients), and/or synovial cysts (66 patients). Reoperations, including for adjacent segment disease (ASD), addressed new/recurrent pathology. RESULTS: Nine (2.7%) of 336 patients required reoperations, including for ASD, an average of 6.3 years (range 2-15 years) following initial 4.7 level laminectomies with 1.4 level noninstrumented fusions. Second operations warranted average 4.8 level (range 3 6) laminectomies and average 1.1 level non instrumented fusions addressing stenosis with instability (Grade I [7 patients] or Grade II [1 patient] spondylolisthesis), new disc herniations (2 patients), and/or a synovial cyst (1 patient). CONCLUSIONS: Only 9 (2.7%) of 336 patients required reoperations (including for ASD) consisting of multilevel laminectomies with noninstrumented fusions for recurrent/new stenosis even with instability; these older patients were not typically unstable, or were likely already fused, and did not require instrumentation. Alternatively, reoperation rates following instrumented fusions in other series approached 80% at 5 postoperative years. Therefore, we as spinal surgeons should realize that older patients even with instability rarely require instrumentation and that the practice of performing instrumented fusions in everyone, irrespective of age, needs to stop. PMID- 27274408 TI - A review: Reduced reoperation rate for multilevel lumbar laminectomies with noninstrumented versus instrumented fusions. AB - BACKGROUND: The reoperation rate, including for adjacent segment disease (ASD), is lower following multilevel lumbar laminectomy with noninstrumented versus instrumented fusions. METHODS: This study reviews selected literature focusing on the reoperation rate, including for ASD, following multilevel laminectomies with noninstrumented versus instrumented fusions. Several prior studies document a 1.3 5.6% reoperation rate following multilevel laminectomy with/without noninstrumented fusions. RESULTS: The reoperation rates for instrumented fusions, including for ASD, are substantially higher. One study cited a 12.2-18.5% frequency for reoperation following instrumented transforaminal lumbar and posterior lumbar interbody fusions (TLIF and PLIFs) at an average of 164 postoperative months. Another study cited a 9.9% reoperation rate for ASD 1 year following PLIF; this increased to 80% at 5 postoperative years. A further study compared 380 patients variously undergoing laminectomies/noninstrumented posterolateral fusions, laminectomies with instrumented fusions (PLFs), and laminectomies with instrumented PLF plus an interbody fusions; this study documented no significant differences in outcomes for any of these operations at 4 postoperative years. Furthermore, other series showed fusion rates for 1-2 level procedures which were often similar with or without instrumentation, while instrumentation increased reoperation rates and morbidity. CONCLUSIONS: Many studies document no benefit for adding instrumentation to laminectomies performed for degenerative disease, including spondylolisthesis. Reoperation rates for laminectomy alone/laminectomy with noninstrumented fusions vary from 1.3% to 5.6% whereas reoperation rates for ASD after instrumented PLIF was 80% at 5 postoperative years. This review should prompt spinal surgeons to reexamine when, why, and whether instrumentation is really necessary, particularly for treating degenerative lumbar disease. PMID- 27274409 TI - Perioperative visual loss following prone spinal surgery: A review. AB - BACKGROUND: Postoperative visual loss (POVL) following prone spine surgery occurs in from 0.013% to 1% of cases and is variously attributed to ischemic optic neuropathy (ION: anterior ION or posterior ION [reported in 1.9/10,000 cases: constitutes 89% of all POVL cases], central retinal artery occlusion [CRAO], central retinal vein occlusion [CRVO], cortical blindness [CB], direct compression [horseshoe, prone pillows, and eye protectors Dupaco Opti-Gard]), and acute angle closure glaucoma (AACG). METHODS: Risk factors for ION include prolonged operative times, long-segment spinal instrumentation, anemia, intraoperative hypotension, diabetes, obesity, male sex, using the Wilson frame, microvascular pathology, decreased the percent of colloid administration, and extensive intraoperative blood loss. Risk factors for CRAO more typically include improper positioning during the surgery (e.g., cervical rotation), while those for CB included prone positioning and obesity. RESULTS: POVL may be avoided by greater utilization of crystalloids versus colloids, administration of alpha-2 agonists (e.g., decreases intraocular pressure), avoidance of catecholamines (e.g., avoid vasoconstrictors), avoiding intraoperative hypotension, and averting anemia. Patients with glaucoma or glaucoma suspects may undergo preoperative evaluation by ophthalmologists to determine whether they require prophylactic treatment prior to prone spinal surgery and whether and if prophylactic treatment is warranted. CONCLUSIONS: The best way to avoid POVL is to recognize its multiple etiologies and limit the various risk factors that contribute to this devastating complication of prone spinal surgery. Furthermore, routinely utilizing a 3-pin head holder will completely avoid ophthalmic compression, while maintaining the neck in a neutral posture, largely avoiding the risk of jugular vein and/or carotid artery compromise and thus avoiding increasing IOP. PMID- 27274410 TI - Imaging characteristic analysis of metastatic spine lesions from breast, prostate, lung, and renal cell carcinomas for surgical planning: Osteolytic versus osteoblastic. AB - BACKGROUND: Surgeons treating metastatic spine disease can use computed tomography (CT) imaging to determine whether lesions are osteolytic, osteoblastic, or mixed. This enables treatment that considers the structural integrity of the vertebral body (VB), which is impaired with lytic lesions but not blastic lesions. The authors analyzed CT imaging characteristics of spine metastasis from breast, lung, prostate, and renal cell carcinomas (RCCs) to determine the metastasis patterns of each of these common tumors. METHODS: The authors identified patients with metastatic spine disease treated during a 3-year period. Variables studied included age, sex, and cancer type. Lesions from breast, lung, prostate, and RCC primary lesions were selected for imaging analysis. RESULTS: Sixty-six patients were identified: 17 had breast metastasis, 14 prostate, 18 lung, and 17 RCC. Breast cancer metastasis involved 33% of VBs with 56%, 20%, and 24% osteolytic, osteoblastic, and mixed, respectively. Prostate cancer metastasis involved 35% of VBs with 14%, 62%, and 24% osteolytic, osteoblastic, and mixed, respectively. Lung cancer metastasis involved 13% of VBs with 64%, 33%, and 3% osteolytic, osteoblastic, and mixed, respectively. RCC metastasis involved 11% of VBs with 91%, 7%, and 2% osteolytic, osteoblastic, and mixed lesions, respectively. CONCLUSIONS: To improve surgical planning, we advocate the use of CT prior to surgery to evaluate whether spine metastases are osteolytic or osteoblastic. In cases of osteolytic lesions, the concern is of segmental instability requiring reconstruction and the risk for screw pull out should instrumentation be considered. In cases of osteoblastic lesions, surgeons should consider debulking dense bone. PMID- 27274411 TI - Traumatic spondyloptosis at the cervico-thoracic junction without neurological deficits. AB - BACKGROUND: There have been rare cases of traumatic cervical spondyloptosis without neurological compromise. We report another case and provide a review of the literature, with a focus on appropriate management. CASE DESCRIPTION: A 60 year-old male rode his bicycle into a stationary semi-truck. He reported initial bilateral upper extremity paresthesias that resolved. Imaging demonstrated C7 on T1 spondyloptosis. Traction did not achieve reduction and a halo was applied. Subsequently, he underwent posterior decompression C6-T1, reduction via bilateral complete facetectomies at C7, and fixation from C4 to T2 fixation. Afterward, an anterior C7-T1 fixation occurred, where exposure was performed through a midline sternotomy. Postoperatively, he woke up with baseline motor and sensory examination in his extremities. He did exhibit voice hoarseness due to paralysis of the left vocal cords. He was discharged home 3 days after surgery. At 6 months follow-up, there was a progressive improvement of the left vocal cords to slight paresis; dynamic X-rays demonstrated no instability with good fusion progression. CONCLUSION: Traumatic cervical spondyloptosis without neurological compromise is a rare and challenging scenario. There is a concern for neurologic compromise with preoperative traction, but if specific posterior elements are fractured, the spinal canal may be wide enough where the concern for disc migration is minimal. For patients who have not been reduced preoperatively, a posterior approach with initial decompression to widen the canal, before reduction, appears safe. This scheme may avoid an initial anterior approach for decompression, necessitating a 3-stage procedure if circumferential stabilization is pursued. PMID- 27274412 TI - Chondromyxoid fibroma of the sacrum: A case report and literature review. AB - BACKGROUND: Chondromyxoid fibroma (CMF) is an extremely rare, benign cartilaginous tumor that makes up <0.5% of all bone tumors, typically presenting in the second or third decade of life. CMF of the sacrum is exceedingly rare, with only seven documented cases reported in the neurosurgical literature. CASE DESCRIPTION: We report a case of a 35-year-old female with a 3 month history of lower back pain after sustaining a fall on her sacrum/coccyx presenting with a progressive complaint of localized lower back pain, occasional urinary retention without incontinence, gluteal hypesthesia, and pressure below the gluteal crease. Imaging demonstrated a large, expansile enhancing soft-tissue lesion involving the sacrum, distal to the S2-3 disc space. The tumor was removed with partial sacrectomy for open en bloc resection with partial nerve sparing. The patient was found at 1.5-year follow-up with the improvement of symptoms, no recurrence, and no residual neurologic dysfunction. CONCLUSION: Sacral CMF is a rare clinical entity that may mirror more aggressive sacral pathology, including chordoma, in both clinical presentation and imaging characteristics. A review of the available literature regarding diagnosis, surgical management options, and prognosis for sacral CMF is provided. PMID- 27274414 TI - Effect of Picture Archiving and Communication System Image Manipulation on the Agreement of Chest Radiograph Interpretation in the Neonatal Intensive Care Unit. AB - OBJECTIVE: Variability in image interpretation has been attributed to differences in the interpreters' knowledge base, experience level, and access to the clinical scenario. Picture archiving and communication system (PACS) has allowed the user to manipulate the images while developing their impression of the radiograph. The aim of this study was to determine the agreement of chest radiograph (CXR) impressions among radiologists and neonatologists and help determine the effect of image manipulation with PACS on report impression. MATERIALS AND METHODS: Prospective cohort study included 60 patients from the Neonatal Intensive Care Unit undergoing CXRs. Three radiologists and three neonatologists reviewed two consecutive frontal CXRs of each patient. Each physician was allowed manipulation of images as needed to provide a decision of "improved," "unchanged," or "disease progression" lung disease for each patient. Each physician repeated the process once more; this time, they were not allowed to individually manipulate the images, but an independent radiologist presets the image brightness and contrast to best optimize the CXR appearance. Percent agreement and opposing reporting views were calculated between all six physicians for each of the two methods (allowing and not allowing image manipulation). RESULTS: One hundred percent agreement in image impression between all six observers was only seen in 5% of cases when allowing image manipulation; 100% agreement was seen in 13% of the cases when there was no manipulation of the images. CONCLUSION: Agreement in CXR interpretation is poor; the ability to manipulate the images on PACS results in a decrease in agreement in the interpretation of these studies. New methods to standardize image appearance and allow improved comparison with previous studies should be sought to improve clinician agreement in interpretation consistency and advance patient care. PMID- 27274413 TI - Intramedullary spinal cord metastasis arising from papillary thyroid carcinoma: A case report and review of literature. AB - BACKGROUND: Intramedullary spinal cord metastases (IMSCM) are typically drop lesions from intracranial metastases and are a rare manifestation of systemic malignancy (8.5% of central nervous system metastases). They arise from primaries such as the lungs, breast, kidney, melanoma, or lymphoma. On the other hand, they arise very rarely from papillary thyroid carcinoma (PTC), even though it is the most common type of primary thyroid malignancy. CASE DESCRIPTION: A 54-year-old male presented with pain in the lower back along with tingling, numbness, and weakness in the bilateral lower limbs. This was associated with urine incontinence for 11/2 months. In the previous month, he developed a left-sided solitary thyroid nodule. Fine needle aspiration cytology and ultrasonography were suggestive of metastasis. Furthermore, the thoracolumbar magnetic resonance imaging showed T1-hypo and T2-hyper-intense D11-D12 level intramedullary lesion, with intense enhancement, which was consistent with an intramedullary lesion involving the conus. At surgery, a firm, brownish yellow, friable, vascular tumour was removed en toto. Upon discharge, the patient was neurologically intact except for residual bladder incontinence. CONCLUSION: In an extensive literature review (pubmed), IMSCM metastasis from PTC primary is confirmed as a rarity and this may be the fourth documented case. Moreover, this may be the first report of a case of PTC metastatic neurological deterioration "even before the treatment of the primary was undertaken." Early diagnosis and microsurgical resection can result in improvement of neurological deficits and in the quality of life of patients with IMSCM. PMID- 27274415 TI - A Review of Energy Drinks and Mental Health, with a Focus on Stress, Anxiety, and Depression. AB - Background: Concerns have been expressed regarding the potential for caffeinated energy drinks to negatively affect mental health, and particularly so in young consumers at whom they are often targeted. The products are frequently marketed with declarations of increasing mental and physical energy, providing a short term boost to mood and performance. Although a certain amount of evidence has accumulated to substantiate some of these claims, the chronic effects of energy drinks on mental health also need to be addressed. Methods: To review the relevant literature, PubMed and PsycINFO were searched for all peer-reviewed articles published in English that addressed associations between energy drink use and mental health outcomes. Case reports were also considered, though empirical studies investigating acute mood effects were excluded as a review of such articles had recently been published. Fifty-six articles were retrieved: 20 of these (along with eight more identified through other means) were included in the current review, and, because the majority addressed aspects of stress, anxiety, and depression, particular focus was placed on these outcomes. Results: Though a number of null findings (and one negative relationship) were observed, the majority of studies examined reported positive associations between energy drink consumption and symptoms of mental health problems. Conclusions: Though the findings imply that energy drink use may increase the risk of undesirable mental health outcomes, the majority of research examined utilized cross-sectional designs. In most cases, it was therefore not possible to determine causation or direction of effect. For this reason, longitudinal and intervention studies are required to increase our understanding of the nature of the relationships observed. PMID- 27274416 TI - Energy Drink and Coffee Consumption and Psychopathology Symptoms Among Early Adolescents: Cross-Sectional and Longitudinal Associations. AB - Background: Little is known about possible links between energy drink use and psychopathology among youth. This study examined cross-sectional and longitudinal associations between energy drink consumption and psychopathology among early adolescents. In addition, associations between psychopathology and coffee consumption were examined to assess whether findings were specific to energy drinks or also applied to another commonly used caffeinated beverage. Methods: One hundred forty-four youth who participated in the Camden Youth Development Study (72 males; mean age 11.9 at wave 1; 65% Hispanic, 30% African American) were assessed using self-report measures of frequency of energy drink and coffee consumption and depression, anxiety, conduct disorder (CD) symptoms, and teacher reports of attention-deficit hyperactivity disorder (ADHD). Youth (92%) were reassessed 16 months later. Results: Concurrently, energy drink and coffee consumption were associated with similar psychopathology symptoms; when the other beverage was adjusted for, energy drinks remained associated with CD and coffee remained associated with panic anxiety. Initial energy drink consumption predicted increasing ADHD and CD over time, though the association with CD dropped to a trend level of significance when coffee was adjusted for. Initial levels of hyperactive ADHD predicted increasing coffee consumption over time; this association remained when energy drinks were controlled. Social anxiety was associated with less increase in energy drink consumption over time, controlling for coffee. Conclusion: Energy drink and coffee consumption among early adolescents are concurrently associated with similar psychopathology symptoms. Longitudinally, the associations between these beverages and psychopathology differ, indicating that these substances have differing implications for development over time. PMID- 27274417 TI - Demographics, Health, and Risk Behaviors of Young Adults Who Drink Energy Drinks and Coffee Beverages. AB - Objective: The present study investigates risk behaviors, sleep habits, and mental health factors associated with caffeinated beverage use in young adults. Materials and Methods: Students from a midsize private university (n = 159) completed a 15-minute anonymous questionnaire, including questions on risk behaviors, sleep habits, alcohol, and caffeine consumption. We compared behaviors between the top ~15% ("high end") of energy drink users (>=3/month) and coffee users (>=16/month) to those with less frequent or no caffeine consumption. Results: Caffeine consumption was frequent among young adults. In the last month, 36% of students had an energy drink, 69% had coffee or espresso, and 86% reported having any caffeine; however, the majority of students were unaware of the caffeine content in these beverages. High-end energy drink consumers reported more risk-taking behaviors (increased drug and alcohol use and less frequent seat belt use), sleep disturbances (later bedtimes, harder time falling asleep, and more all-nighters), and higher frequency of mental illness diagnoses than those who consumed fewer energy drinks. In contrast, the frequency of most risk behaviors, sleep disturbances, and mental illness diagnoses was not significantly different between the high-end and general population of coffee drinkers. Conclusion: Students with delayed sleep patterns, mental illness, and higher frequency of substance use and risk behaviors were more likely to be regular energy drink users but not regular coffee drinkers. It is unclear whether the psychoactive content in energy drinks results in different behavioral effects than just caffeine in coffee, and/or different personality/health populations are drawn to the two types of beverages. PMID- 27274418 TI - A SYSTEMATIC REVIEW OF THE EXERCISES THAT PRODUCE OPTIMAL MUSCLE RATIOS OF THE SCAPULAR STABILIZERS IN NORMAL SHOULDERS. AB - PURPOSE: The purpose of this systematic review was to determine the exercises that optimize muscle ratios of the periscapular musculature for scapular stability and isolated strengthening. METHODS: A systematic search was performed in PubMed, CINAHL, SPORTDiscus, Scopus, and Discovery Layer. Studies were included if they examined the muscle activation of the upper trapezius compared to the middle trapezius, lower trapezius, or serratus anterior using EMG during open chain exercises. The participants were required to have healthy, nonpathological shoulders. Information obtained included maximal voluntary isometric contraction (MVIC) values, ratios, standard deviations, exercises, and exercise descriptions. The outcome of interest was determining exercises that create optimal muscle activation ratios between the scapular stabilizers. RESULTS: Fifteen observational studies met the inclusion criteria for the systematic review. Exercises with optimal ratios were eccentric exercises in the frontal and sagittal planes, especially flexion between 180 degrees and 60 degrees . External rotation exercises with the elbow flexed to 90 degrees also had optimal ratios for activating the middle trapezius in prone and side-lying positions. Exercises with optimal ratios for the lower trapezius were prone flexion, high scapular retraction, and prone external rotation with the shoulder abducted to 90 degrees and elbow flexed. Exercises with optimal ratios for the serratus anterior were the diagonal exercises and scapular protraction. CONCLUSION: This review has identified optimal positions and exercises for periscapular stability exercises. Standing exercises tend to activate the upper trapezius at a higher ratio, especially during the 60-120 degrees range. The upper trapezius was the least active, while performing exercises in prone, side lying, and supine positions. More studies need to be conducted to examine these exercises in greater detail and confirm their consistency in producing the optimal ratios determined in this review. LEVEL OF EVIDENCE: 1a. PMID- 27274419 TI - THE RELATIONSHIP BETWEEN CORE ENDURANCE AND BACK DYSFUNCTION IN COLLEGIATE MALE ATHLETES WITH AND WITHOUT NONSPECIFIC LOW BACK PAIN. AB - BACKGROUND: Physical activity and sports can be associated with low back pain. However, little is known about the relationship between core stability and nonspecific low back pain (LBP) among athletes. PURPOSE: The purpose of this study was to investigate the relationship between core endurance and back dysfunction in collegiate male athletes with and without nonspecific LBP. METHODS: Fifty-five male collegiate athletes from a variety of sports were recruited for this study. Their mean age was 21.50 +/- (2.54) years, mean weight was 70.96 +/- (5.33) kg., and mean height was 174.38 +/- (4.37) cm. Thirty athletes with non-specific LBP and twenty five healthy athletes were assessed using McGill's anterior, posterior, and left and right plank core endurance tests (seconds) and for dysfunction using the Micheli functional scale (MFS). Pearson's product moment correlations examined the relationships between core endurance and MFS. RESULTS: There were significant differences regarding the measured core endurance tests between the healthy athletes group and the nonspecific LBP group (p < 0.05). Additionally, good negative (r = -0.794) and moderate negative (r = 0.541) correlations were found between MFS and trunk extensor and flexor endurance tests, respectively in the group with nonspecific LBP. CONCLUSION: The results of this study imply that poor core endurance is likely associated with nonspecific LBP in collegiate athletes. Injury risk reduction and back management programs for the athletic population should include strategies that emphasize endurance of the core muscles especially the trunk extensors and flexors. LEVEL OF EVIDENCE: 2b. PMID- 27274420 TI - ASSOCIATION BETWEEN ROWING INJURIES AND THE FUNCTIONAL MOVEMENT SCREENTM IN FEMALE COLLEGIATE DIVISION I ROWERS. AB - BACKGROUND: 48 percent of rowing injuries are due to overuse and occur more often in females. The Functional Movement ScreenTM (FMS) is a screening tool utilized to identify the risk of musculoskeletal injury in field sport athletes based on movement patterns. It has not been used to identify risk of injury in rowing. OBJECTIVES: The purpose of this study was to determine if the scores on the FMSTM are predictors of incidence of all injuries, including low back pain (LBP) in female collegiate rowers during one season of rowing. METHODS: Prospective cohort conducted in a clinical setting. Thirty-seven Division I female collegiate rowers (33 rowers and 4 coxswains). Investigators performed pre-season FMSTM screening and collected demographic data, rowing data, and Oswestry Low Back Pain questionnaire scores. Based on FMSTM scores, individuals were grouped high or low risk for injury. Injury reports and patient complaints of LBP over the course of a season were compared to FMSTM group. RESULTS: Those in the high risk group were significantly more likely to experience LBP during the season (p=.036) and reported a 58 percent greater mean in years of rowing experience (p=.008) than individuals in the low risk group. Those with a history of LBP were six times more likely to experience LBP during season (p=.027). DISCUSSION: The FMSTM indicated that rowers at a high risk of injury and more years of rowing experience, have a higher probability of sustaining LBP. Results could be due to chronic overuse associated with the rowing motion. Low back pain was evident in 25 out of the 37 participants over the season. CONCLUSION: While the FMSTM has been proven to predict injury in field athletes, there was no statistically significant evidence to support prediction of a reported time loss injury in female collegiate rowers. However, it did indicate a higher likelihood for subjective report of low back pain. LEVEL OF EVIDENCE: Cohort study, level 2b. PMID- 27274421 TI - ACCURACY OF SELF-REPORTED FOOT STRIKE PATTERN IN INTERCOLLEGIATE AND RECREATIONAL RUNNERS DURING SHOD RUNNING. AB - BACKGROUND: Clinicians are interested in the foot strike pattern (FSP) in runners because of the suggested relationship between the strike pattern and lower extremity injury. PURPOSE: The purpose of this study was to assess the ability of collegiate cross-country runners and recreational runners to self-report their foot strike pattern during running. STUDY DESIGN: Cross-sectional Study. METHODS: Twenty-three collegiate cross-country and 23 recreational runners voluntarily consented to participate. Inclusion criteria included running at least 18 miles per week, experience running on a treadmill, no history of lower extremity congenital or traumatic deformity, or acute injury three months prior to the start of the study. All participants completed a pre-test survey to indicate their typical foot strike pattern during a training run (FSPSurvey). Prior to running, reflective markers were placed on the posterior midsole and the vamp of the running shoe. A high-speed camera was used to film each runner in standing and while running at his or her preferred speed on a treadmill. The angle between the vector formed by the two reflective markers and the superior surface of the treadmill was used to calculate the foot strike angle (FSA). To determine the foot strike pattern from the video data (FSPVideo), the static standing angle was subtracted from the FSA at initial contact of the shoe on the treadmill. In addition to descriptive statistics, percent agreement and Chi square analysis was used to determine distribution differences between the video analysis results and the survey. RESULTS: The results of the chi-square analysis on the distribution of the FSPSurvey in comparison to the FSPVideo were significantly different for both the XCRunners (p < .01; Chi-square = 8.77) and the REC Runners (p < .0002; Chi-square = 16.70). The cross-country and recreational runners could correctly self-identified their foot strike pattern 56.5% and 43.5% of the time, respectively. CONCLUSION: The findings of this study suggest that the clinician cannot depend on an experienced runner to correctly self-identify their FSP. Clinicians interested in knowing the FSP of a runner should consider performing the two-dimensional video analysis described in this paper. LEVEL OF EVIDENCE: 3. PMID- 27274423 TI - INFLUENCE OF INJURY ON DYNAMIC POSTURAL CONTROL IN RUNNERS. AB - BACKGROUND: Injury has been linked with altered postural control in active populations. The association between running injury and dynamic postural control has not been examined. HYPOTHESIS/PURPOSE: The purpose of this study was to examine dynamic postural control in injured and uninjured runners using the Star Excursion Balance Test (SEBT), Time to Stabilization (TTS) of ground reaction forces following a single-leg landing, and postural stability indices reflecting the fluctuations in GRFs during single-leg landing and stabilization tasks (forward and lateral hop). It was hypothesized that dynamic postural control differences would exist between runners with a history of injury that interrupted training for >=7 days (INJ) when compared to runners without injury (CON). DESIGN: Case-control study. METHODS: Twenty-two INJ (14 F, 8 M; 23.7 +/- 2.1 y; 22.3 +/- 2.8 kg/m2; 29.5 +/- 16.3 mi/wk) currently running > 50% pre-injury mileage without pain were compared with twenty-two matched CON (14F, 8M; 22.7 +/- 1.2 y; 22.7 +/- 2.7 kg/m2; 31.2 +/- 19.6 mi/wk). INJ group was stratified by site of injury into two groups (Hip/Thigh/Knee and Lower Leg/Ankle/Foot) for secondary analysis. Leg length-normalized anterior, posterolateral, and posteromedial reach distances on the SEBT, medial/lateral and anterior/posterior ground reaction force TTS, directional postural stability indices, and a composite dynamic postural stability index (DPSI), were assessed using mixed model ANOVA (alpha=0.05) and effect sizes (d). RESULTS: No group X direction interaction or group differences were observed for the SEBT (p=0.51, 0.71) or TTS (p=0.83, 0.72) measures. A group X direction interaction was found for postural stability indices during the forward landing task (p<0.01). Both Hip/Thigh/Knee and Lower leg/Ankle/Foot INJ groups demonstrated a greater vertical postural stability index (VPSI) (p=0.01 for both, d=0.80, 0.95) and DPSI (p=0.01, 0.02, d=0.75, 0.93) when compared to CON suggesting impaired balance control. A group X direction interaction was also found for postural stability indices during the lateral landing task (p=0.03). Only the Hip/Thigh/Knee INJ runners displayed a greater VPSI (p=0.01, d=0.91) and DPSI (p=0.017, d=0.89) when compared to CON. CONCLUSIONS: When compared to CON, INJ runners demonstrated impaired dynamic control of vertical forces when performing the single leg landing and stabilization tasks. Clinicians should consider addressing dynamic control of vertical loads through functional tasks during the rehabilitation of running injury. LEVEL OF EVIDENCE: Level 3. PMID- 27274422 TI - REPRODUCIBILITY OF THE MODIFIED STAR EXCURSION BALANCE TEST COMPOSITE AND SPECIFIC REACH DIRECTION SCORES. AB - BACKGROUND: The mSEBT is a screening tool used to evaluate dynamic balance. Most research investigating measurement properties focused on intrarater reliability and was done in small samples. To know whether the mSEBT is useful to discriminate dynamic balance between persons and to evaluate changes in dynamic balance, more research into intra- and interrater reliability and smallest detectable change (synonymous with minimal detectable change) is needed. PURPOSE: To estimate intra- and interrater reliability and smallest detectable change of the mSEBT in adults at risk for ankle sprain. STUDY DESIGN: Cross-sectional, test retest design. METHODS: Fifty-five healthy young adults participating in sports at risk for ankle sprain participated (mean +/- SD age, 24.0 +/- 2.9 years). Each participant performed three test sessions within one hour and was rated by two physical therapists (session 1, rater 1; session 2, rater 2; session 3, rater 1). Participants and raters were blinded for previous measurements. Normalized composite and reach direction scores for the right and left leg were collected. Analysis of variance was used to calculate intraclass correlation coefficient values for intra- and interrater reliability. Smallest detectable change values were calculated based on the standard error of measurement. RESULTS: Intra- and interrater reliability for both legs was good to excellent (intraclass correlation coefficient ranging from 0.87 to 0.94). The intrarater smallest detectable change for the composite score of the right leg was 7.2% and for the left 6.2%. The interrater smallest detectable change for the composite score of the right leg was 6.9% and for the left 5.0%. CONCLUSION: The mSEBT is a reliable measurement instrument to discriminate dynamic balance between persons. Most smallest detectable change values of the mSEBT appear to be large. More research is needed to investigate if the mSEBT is usable for evaluative purposes. LEVEL OF EVIDENCE: Level 2. PMID- 27274424 TI - PRE- AND POST-OPERATIVE SELF-REPORTED FUNCTION AND QUALITY OF LIFE IN WOMEN WITH AND WITHOUT GENERALIZED JOINT LAXITY UNDERGOING HIP ARTHROSCOPY FOR FEMOROACETABULAR IMPINGEMENT. AB - BACKGROUND: Generalized joint laxity is more prevalent in women than men and may lead to poorer post-operative outcomes in select orthopedic populations. There are no studies examining peri-operative function in patients with generalized joint laxity (GJL) and femoroacetabular impingement (FAI). PURPOSE: The purpose of this study was to determine the difference in perceived function and quality of life as measured by the Hip Outcome Score ADL subscale (HOS-ADL), International Hip Outcomes Tool (iHOT-33) and the Short Form 12-Item Health Survey (SF-12) in women with and without GJL prior to and six months after undergoing hip arthroscopy for FAI. STUDY DESIGN: Cohort Study. METHODS: Peri operative data were collected from women with FAI from November 2011-September 2014. Lax subjects were women with laxity scores >=4/9 on the Beighton and Horan Joint Mobility Index; Nonlax subjects were women with laxity scores <4/9. Functional outcomes were evaluated using the HOS-ADL, iHOT-33, PCS-12, and the MCS-12 pre-operatively and at 6 months post-operatively. Change scores (post score - pre-score) were calculated for each outcome measure and compared between groups, along with pre-operative and post-operative means, using Mann-Whitney U tests. RESULTS: 166 women met the inclusion criteria: Nonlax (n = 131), Lax (n = 35). There were no statistically significant differences between groups in pre operative functional outcomes (all p > .05). Additionally, there were no statistically significant differences between groups in post-operative means or change scores, respectively, for HOS-ADL (p = .696, .358), iHOT-33 (p = .550, .705), PCS-12 (p = .713, .191), and MCS-12 (p = .751, .082). Laxity score was not associated with any post-operative functional outcome score or change score (all p > .05). CONCLUSION: Women with and without generalized joint laxity do not appear to report differences in hip function in the 6-month peri-operative period before and after hip arthroscopy for FAI. LEVEL OF EVIDENCE: 3. PMID- 27274425 TI - ANKLE JOINT CONTROL DURING SINGLE-LEGGED BALANCE USING COMMON BALANCE TRAINING DEVICES - IMPLICATIONS FOR REHABILITATION STRATEGIES. AB - BACKGROUND: A lateral ankle sprain is the most prevalent musculoskeletal injury in sports. Exercises that aim to improve balance are a standard part of the ankle rehabilitation process. In an optimal progression model for ankle rehabilitation and prevention of future ankle sprains, it is important to characterize different balance exercises based on level of difficulty and sensori-motor training stimulus. PURPOSE: The purpose of this study was to investigate frontal-plane ankle kinematics and associated peroneal muscle activity during single-legged balance on stable surface (floor) and three commonly used balance devices (Airex(r), BOSU(r) Ball and wobble board). DESIGN: Descriptive exploratory laboratory study. METHODS: Nineteen healthy subjects performed single-legged balance with eyes open on an Airex(r) mat, BOSU(r) Ball, wobble board, and floor (reference condition). Ankle kinematics were measured using reflective markers and 3-dimensional recordings and expressed as inversion-eversion range of motion variability, peak velocity of inversion and number of inversion-eversion direction changes. Peroneus longus EMG activity was averaged and normalized to maximal activity during maximum voluntary contraction (MVC), and in addition amplitude probability distribution function (APDF) between 90 and 10% was calculated as a measure of muscle activation variability. RESULTS: Balancing on BOSU(r) Ball and wobble board generally resulted in increased ankle kinematic and muscle activity variables, compared to the other surfaces. BOSU(r) Ball was the most challenging in terms of inversion-eversion variability while wobble board was associated with a higher number of inversion-eversion direction changes. No differences in average muscle activation level were found between these two surfaces, but the BOSU(r) Ball did show a more variable activation pattern in terms of APDF. CONCLUSION: The results showed large kinematic variability among different balance training devices and these differences are also reflected in muscle activation variability. The two most challenging devices were BOSU(r) Ball and Wobble board compared to Airex(r) and floor. This study can serve as guidance for clinicians who wish to implement a gradual progression of ankle rehabilitation and prevention exercises by taking the related ankle kinematics and muscle activity into account. LEVEL OF EVIDENCE: Level 3. PMID- 27274426 TI - PREDICTING FOOT PROGRESSION ANGLE DURING GAIT USING TWO CLINICAL MEASURES IN HEALTHY ADULTS, A PRELIMINARY STUDY. AB - BACKGROUND: The foot progression angle (FPA) is related to the transverse plane rotation of the lower extremities and associated with many lower extremity conditions. PURPOSE: The purpose of this study was to examine how two commonly used clinical measures, tibio-fibular torsion (TF) and hip rotation, can be used to predict FPA during gait in healthy adults. STUDY DESIGN: Cross-sectional study design. METHODS: Passive hip internal and external rotation ranges of motion and TF torsion were measured with a 12-inch goniometer while the FPA (degree of toe in/out) was measured with the GAITRite during midstance in sixty participants. The data was analyzed using a multiple regression model. RESULTS: Hip ER was not significant and was therefore excluded from the final model. The final model included passive hip IR and TF torsion (F = 19.64; p < .001; multiple R(2) = .41; adjusted R(2) = .39). Simple binary correlations showed that hip IR had a moderate negative correlation (r = -.40) with FPA (the greater the hip IR, the greater the in-toeing) while TF torsion had a positive correlation (r = .39) with FPA (the greater the external TF torsion. the greater the out-toeing). CONCLUSIONS: Greater amount of passive hip IR predicts in-toeing while greater TF torsion predicts out-toeing of the foot during midstance phase of gait. LEVEL OF EVIDENCE: Level 2. PMID- 27274428 TI - PHYSICAL THERAPY INTERVENTION FOR MEDIAL PATELLOFEMORAL LIGAMENT RECONSTRUCTION AFTER REPEATED LATERAL PATELLAR SUBLUXATION/DISLOCATION. AB - BACKGROUND: The incidence of patellar subluxation or dislocation has been documented up to 43/100,000 with females more prevalent then males. There are many contributing factors involving the hip, knee, and ankle that lead to patellar subluxation. A patellar position of lateral tilt with lateral glide may indicate weakness of the vastus medialis oblique (VMO) and adductors, increased tightness in the iliotibial band, and overpowering of the vastus lateralis. Patella alta can predispose an individual to lateral dislocation due to the patella placement outside of the femoral trochlear groove with a disadvantage of boney stability. Other factors that may cause the patella to laterally sublux or dislocate during a functional activity or sporting activity include a position of femoral external rotation, tibial internal rotation, and excessive contraction of the vastus lateralis. The medial patellofemoral ligament (MPFL) aids in the prevention of a lateral patellar subluxation or dislocation. In cases where there is recurrent subluxation/dislocation and Magnetic Resonance Imaging confirms a MPFL tear, a reconstruction may be the treatment of choice. PURPOSE: The purpose of this case series is to describe the post-surgical physical therapy management of MPFL reconstructions, outcomes using the Modified Cincinnati Knee Outcome Measure (MCKOM) and to propose staged physical therapy interventions for this pathology in the form of a treatment progression. METHODS: Post-operative management data and outcomes were retrospectively collected using a detailed chart review methodology from seven subjects who underwent MPFL reconstruction. FINDINGS: The Modified Cincinnati Knee Outcome Measure (MCKOM) was analyzed for each participant in four sections that were most important to the return and maintenance of participation in sport. At follow-up the mean scores for the seven subjects in Section 3 (instability) was 19.3/20, Section 4 (overall activity level) was 17.3/20, Section 7 (running activity) was 4.5/5, and Section 8 (jumping and twisting) was 4.3/5. Overall all subjects scored over an 80 which indicated excellent results for return to activity/sport. CONCLUSIONS: In this case series, seven subjects after MPFL reconstruction returned to sport or functional activity following a physical therapy treatment progression including proprioceptive-focused, and dynamic rehabilitation, along with a home exercise program. Based on these positive results and a review of relevant literature regarding MPFL rehabilitation, a rehabilitation progression was presented. LEVEL OF EVIDENCE: Level 4- Case Series. PMID- 27274427 TI - STRENGTH EXERCISES COMBINED WITH DRY NEEDLING WITH ELECTRICAL STIMULATION IMPROVE PAIN AND FUNCTION IN PATIENTS WITH CHRONIC ROTATOR CUFF TENDINOPATHY: A RETROSPECTIVE CASE SERIES. AB - BACKGROUND AND PURPOSE: Rotator cuff tendinopathy (RTCT) is regularly treated by the physical therapist. Multiple etiologies for RTCT exist, leading an individual to seek treatment from their provider of choice. Strengthening exercises (SE) have been reported to be effective in the treatment of RTCT, but there is limited evidence on the effectiveness of dry needing (DN) for this condition. The purpose of this retrospective case series was to investigate DN to various non-trigger point-based anatomical locations coupled with strengthening exercises (SE) as a treatment strategy to decrease pain and increase function in healthy patients with chronic RTC pathology. CASE DESCRIPTIONS: Eight patients with RTCT were treated 1-2 times per week for up to eight weeks, and no more than sixteen total treatment sessions of SE and DN. Outcomes were tested at baseline and upon completion of therapy. A long-term outcome measure follow up averaging 8.75 months (range 3 to 20 months) was also performed. The outcome measures included the Visual Analog Scale (VAS) and the Quick Dash (QD). OUTCOMES: Clinically meaningful improvements in disability and pain in the short term and upon long term follow up were demonstrated for each patient. The mean VAS was broken down into best (VAS(B)), current (VAS(C)), and worst (VAS(W)) rated pain levels and the mean was calculated for the eight patients. The mean VAS(B) improved from 22.5 mm at the initial assessment to 2.36 mm upon completion of the intervention duration. The mean VASC improved from 28.36 mm to 5.0 mm, and the mean VAS(W) improved from 68.88 mm to 13.25 mm. At the long-term follow up (average 8.75 months), The mean VAS(B), VAS(C), and VAS(W) scores were 0.36 mm, 4.88 mm, and 17.88 mm respectively. The QD(mean) for the eight patients improved from 43.09 at baseline to 16.04 at the completion of treatment. At long-term follow-up, the QD(mean) was 6.59. CONCLUSION: Clinically meaningful improvements in pain and disability were noted with the intervention protocol. All subjects responded positively to the intervention and reported quality of life was improved for each subject. The results of this case series show promising outcomes for the combination of SE and DN in the treatment of chronic RTCT. LEVEL OF EVIDENCE: Level 4. PMID- 27274429 TI - A MULTIDISCIPLINARY APPROACH TO THE REHABILITATION OF A COLLEGIATE FOOTBALL PLAYER FOLLOWING ANKLE FRACTURE: A CASE REPORT. AB - BACKGROUND AND PURPOSE: Multiple rehabilitation factors including overall wellness need to be considered when an athlete returns to sport after an injury. The purpose of this case report is to describe a multidisciplinary approach for return to sport of a Division I collegiate football player following a traumatic ankle fracture requiring surgical repair. The assessment and treatment approach included the use of a performance-based physical therapy outcome measure, self reported functional abilities, body composition assessments, and nutritional counseling. CASE DESCRIPTION: A 21 year-old running back fractured his lateral malleolus due to a mechanism of injury of excessive eversion with external rotation of the ankle. Surgical intervention included an open reduction internal fixation (ORIF) of the fibula and syndesmosis. In addition to six months of rehabilitation, the patient received consultations from the team sports nutritionist specialist to provide dietary counseling and body composition testing. The Comprehensive High-level Activity Mobility Predictor-Sport (CHAMP S), a performance-based outcome measure, self-report on the Foot and Ankle Disability Index (FADI-ADL, FADI-S), and body composition testing using whole body densitometry (BOD POD(r)), were administered throughout rehabilitation. OUTCOMES: The subject was successfully rehabilitated, returned to his starting role, and subsequently was drafted by a National Football League (NFL) franchise. High-level mobility returned to above pre-injury values, achieving 105% of his preseason CHAMP-S score at discharge. Self-reported function on the FADI-ADL and FADI-Sport improved to 100% at discharge. Body fat percentages decreased (13.3% to 11.9%) and fat mass decreased (12.0 kg to 11.0kg). Lean body mass (78.1 kg to 81.5 kg) and lbm/in increased (1.14 kg/in to 1.19 kg/in). His BMI changed from 29.8 kg/m(2) to 30.6 kg/m(2). DISCUSSION: This case report illustrates the positive effects of a multidisciplinary approach where combining physical therapy and nutritional counseling demonstrated value with return to sport preparation and success following ankle fracture. A targeted physical therapy program combined with a personalized nutrition intervention based on body composition assessment assisted this athlete in avoiding deconditioning (atrophy, decreased aerobic capacities, and increases in body fat) often observed during postoperative care. LEVEL OF EVIDENCE: 5. PMID- 27274430 TI - TIBIOFEMORAL JOINT MOBILIZATION IN THE SUCCESSFUL MANAGEMENT OF PATELLOFEMORAL PAIN SYNDROME: A CASE REPORT. AB - BACKGROUND AND PURPOSE: Patellofemoral pain syndrome (PFPS) is a common source of anterior knee pain. Controversy exists over the exact clinical findings which define PFPS, thus, diagnosis and management can be challenging for clinicians. There is paucity in the literature concerning joint mobilization as treatment for PFPS, particularly at the tibiofemoral joint, as standard management is currently focused on therapeutic exercise, orthotics, bracing and taping. Therefore, the purpose of this case report is to describe the effects of tibiofemoral joint mobilization in the successful treatment of an individual with chronic PFPS as it relates to pain, function and central processing of pain. STUDY DESIGN: Case Report. CASE DESCRIPTION: The subject was a 28-year-old female with a two year history of left anterior, inferior patellar knee pain consistent with chronic PFPS. She demonstrated diminished pressure pain threshold (PPT) and allodynia at the anterior knee, suggesting a component of central sensitization to her pain. She met several common diagnostic criteria for PFPS, however, only tibiofemoral anterior-posterior joint mobilization increased her pain. Subsequent treatment sessions (Visits 1-6) consisted of solely joint mobilization supplemented by instruction in a home exercise program (therapeutic exercise and balance training). As outcomes improved, treatment sessions (Visits 7-8) consisted of solely therapeutic exercise and balance training with focus on return to independent pain free functional activity. OUTCOMES: Improvements consistent with the minimally clinically important difference were noted on the Kujala Anterior Knee Pain Scale, Numeric Pain Rating Scale, Global Rating of Change (GROC). Scores on the Fear Avoidance-Belief Questionnaire (6/24 to 2/24 PA, 31/42 to 5/42 W), PPT (119 to 386 kPa) and Step Down Test (11 to 40 steps) also demonstrated improvement. At a two month follow up, the subject reported continued improvement in functional activity, 0/10 pain and GROC = +5. DISCUSSION: This case describes the successful use of tibiofemoral joint mobilization in a subject with chronic PFPS and supports the use of joint mobilization as management in PFPS, particularly in cases where a centrally mediated component of pain may be present. LEVEL OF EVIDENCE: Therapy, Level 5. PMID- 27274432 TI - PHYSICAL THERAPY MANAGEMENT OF ICE HOCKEY ATHLETES: FROM THE RINK TO THE CLINIC AND BACK. AB - BACKGROUND: The increasing number of athletes playing hockey compels rehabilitation professionals working in orthopedic and sports settings to understand the unique functional demands of ice hockey and the patterns of injuries they may promote. PURPOSE: The purpose of this clinical perspective is to: (1) discuss the functional implications of different positions and age levels on injury prevalence within the sport; (2) summarize the seven most common injuries sustained by ice hockey athletes; and (3) present a conceptual model for the clinical management and prevention of these injuries by rehabilitation professionals. METHODS: A narrative review and synthesis was conducted of currently available literature on prevalence, etiology, rehabilitative intervention, prognosis, and prevention of ice hockey injuries. RESULTS: Research evidence is available to support the prevalence of injuries sustained while participating in ice hockey, as well as the most effective clinical treatment protocols to treat them. Most of the existing protocols are based on clinical and sports experience with incorporation of scientific data. CONCLUSION: This clinical commentary reviews the current concepts of ice hockey injury care and prevention, based on scientific information regarding the incidence, mechanism, rehabilitation protocols, prognosis, and prevention of injuries. Science-based, patient-centered reasoning is integral to provide the highest quality of rehabilitative and preventative care for ice hockey athletes by physical therapists. LEVEL OF EVIDENCE: 5. PMID- 27274433 TI - CORRIGENDUM. AB - [This corrects the article on p. 868 in vol. 10, PMID: 15976421.]. PMID- 27274431 TI - PARTIAL ARTICULAR SUPRASPINATUS TENDON AVULSION (PASTA) LESION. CURRENT CONCEPTS IN REHABILITATION. AB - Rotator cuff pathology can contribute to shoulder pain and may affect the performance of sport activities, work, and activities of daily living. The partial articular supraspinatus tendon avulsion (PASTA) lesion represents a very common type of rotator cuff pathology seen in rehabilitation. When conservative treatment fails, surgery is generally required. Success of recovery depends on several factors, including: repair techniques, healing process related to timing, rehabilitation programs, and patient compliance with home exercises. To date, most treatment modalities and rehabilitation programs are based on clinical experience rather than scientific evidence. Therefore, the purpose of this clinical commentary is to provide an overview on the PASTA lesion, discuss the common treatment approaches adopted to date and to propose a rehabilitation program based on the available scientific evidence. LEVEL OF EVIDENCE: 5. PMID- 27274434 TI - Analysis of the Molecular Mechanisms of Reepithelialization in Drosophila Embryos. AB - Significance: The epidermis provides the main barrier function of skin, and therefore its repair following wounding is an essential component of wound healing. Repair of the epidermis, also known as reepithelialization, occurs by collective migration of epithelial cells from around the wound edge across the wound until the advancing edges meet and fuse. Therapeutic manipulation of this process could potentially be used to accelerate wound healing. Recent Advances: It is difficult to analyze the cellular and molecular mechanisms of reepithelialization in human tissue, so a variety of model organisms have been used to improve our understanding of the process. One model system that has been especially useful is the embryo of the fruit fly Drosophila, which provides a simple, accessible model of the epidermis and can be manipulated genetically, allowing detailed analysis of reepithelialization at the molecular level. This review will highlight the key insights that have been gained from studying reepithelialization in Drosophila embryos. Critical Issues: Slow reepithelialization increases the risk of wounds becoming infected and ulcerous; therefore, the development of therapies to accelerate or enhance the process would be a great clinical advance. Improving our understanding of the molecular mechanisms that underlie reepithelialization will help in the development of such therapies. Future Directions: Research in Drosophila embryos has identified a variety of genes and proteins involved in triggering and driving reepithelialization, many of which are conserved in humans. These novel reepithelialization proteins are potential therapeutic targets and therefore findings obtained in Drosophila may ultimately lead to significant clinical advances. PMID- 27274435 TI - Drosophila Imaginal Discs as a Model of Epithelial Wound Repair and Regeneration. AB - Significance: The Drosophila larval imaginal discs, which form the adult fly during metamorphosis, are an established model system for the study of epithelial tissue damage. The disc proper is a simple columnar epithelium, but it contains complex patterning and cell-fate specification, and is genetically tractable. These features enable unbiased genetic screens to identify genes involved in all aspects of the wound response, from sensing damage to wound closure, initiation of regeneration, and re-establishment of proper cell fates. Identification of the genes that facilitate epithelial wound closure and regeneration will enable development of more sophisticated wound treatments for clinical use. Recent Advances: Imaginal disc epithelia can be damaged in many different ways, including fragmentation, induction of cell death, and irradiation. Recent work has demonstrated that the tissue's response to damage varies depending on how the wound was induced. Here, we summarize the different responses activated in these epithelial tissues after the different types of damage. Critical Issues: These studies highlight that not all wounds elicit the same response from the surrounding tissue. A complete understanding of the various wound-healing mechanisms in Drosophila will be a first step in understanding how to manage damaged human tissues and optimize healing in different clinical contexts. Future Directions: Further work is necessary to understand the similarities and differences among an epithelial tissue's responses to different insults. Ongoing studies will identify the genes and pathways employed by injured imaginal discs. Thus, work in this genetically tractable system complements work in more conventional wound-healing models. PMID- 27274436 TI - Drosophila Embryos as a Model for Wound-Induced Transcriptional Dynamics: Genetic Strategies to Achieve a Localized Wound Response. AB - While many studies have established a paradigm for tissue repair at the level of cellular remodeling, it is not clear how an organism restricts a response only to the injured region of a damaged tissue. Skin, the largest organ in the human body, is prone to injury, and repair of epidermal tissue represents a medically relevant system to investigate. Significance: Studies in Drosophila melanogaster provide a robust genetic system to identify molecular components that will positively impact repair and healing. The Drosophila skin consists of a single cell epidermal layer and relies on well-conserved cellular mechanisms to coordinate gene expression during development. Many studies have established that key developmental genes promote a response to epidermal injury, but the balance between activator and inhibitor signals to coordinate a localized response remains unknown. Recent Advances: Discovery of a genetic pathway that promotes the restriction of transcriptional response to damage only in effected regions. Interestingly, genome-wide microarray studies have identified an intersection between gene expression after aseptic injury and activation of the innate immune response. Critical Issues: The use of a transcriptional activation reporter provides an innovative approach to uncover well-conserved components that promote the localization of a response during epidermal injury and may influence other pathological conditions of tissue damage. Future Directions: The work reviewed in this critical review may lead to development of molecular strategies of repair and improved healing after injury or infection. The outcomes on the fundamental contribution of a transcriptional response to injury will be translatable to mammalian systems. PMID- 27274437 TI - Wound-Induced Polyploidy Is Required for Tissue Repair. AB - Significance: All organs suffer wounds to some extent during an animal's lifetime and to compensate for cell loss, tissues often rely on cell division. However, many organs are made up of differentiated cells with only a limited capacity to divide. It is not well understood how cells are replaced in the absence of cell division. Recent Advances: Recent studies in the model organism Drosophila melanogaster have proven that wound-induced polyploidy (WIP) is an essential mechanism to replace tissue mass and restore tissue integrity in the absence of cell division. In this repair mechanism, preexisting differentiated cells increase their DNA content and cell size by becoming polyploid. Critical Issues: Cells within mammalian organs such as the liver, heart, and cornea have also been observed to increase their DNA ploidy in response to injury, suggesting that WIP may be an evolutionarily conserved mechanism to compensate for cell loss. Future Directions: The Hippo signal transduction pathway is required for differentiated cells to initiate WIP in Drosophila. Continued studies in Drosophila will help to identify other signaling pathways required for WIP as well as the conserved mechanisms that polyploid cells may play during wound repair in all organisms. PMID- 27274438 TI - Orotate phosphoribosyltransferase is overexpressed in malignant pleural mesothelioma: Dramatically responds one case in high OPRT expression. AB - OBJECTIVE: Malignant pleural mesothelioma (MPM) is a rare and aggressive, treatment-resistant cancer. Pemetrexed, an inhibitor of thymidylate synthase (TS), is used worldwide for MPM as a first-line chemotherapy regimen. However, there is little consensus for a second-line chemotherapy. S-1, a highly effective dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidine, mainly acts via a TS inhibitory mechanism similar to pemetrexed. Orotate phosphoribosyltransferase (OPRT) is a key enzyme related to the first step activation of 5-fluorouracil (5-FU) for inhibiting RNA synthesis. We investigated 5-FU related-metabolism proteins, especially focusing on OPRT expression, in MPM Methods and Patients: Fifteen MPM patients who were diagnosed between July 2004 and December 2013 were enrolled. We examined the protein levels of 5-FU metabolism-related enzymes (TS, DPD, OPRT, and thymidine phosphorylase [TP]) in 14 cases RESULTS: High TS, DPD, OPRT, and TP expressions were seen in 28.6%, 71.4%, 85.7%, and 35.7% of patients, respectively. We found that OPRT expression was extremely high in MPM tissue. We experienced one remarkable case of highly effective S-1 combined therapy for pemetrexed refractory MPM. This case also showed high OPRT protein expression Conclusion: The present study suggests that OPRT expression is high in MPM tumors. Although pemetrexed is mainly used for MPM chemotherapy as a TS inhibitor, S-1 has potential as an anticancer drug not only as a TS inhibitor but also inhibiting RNA synthesis through the OPRT pathway. This is the first report investigating OPRT protein expressions in MPM. PMID- 27274439 TI - Davis flap: the glory still present. AB - BACKGROUND: Upper third defects of the ear are too large to be closed primarily without distorting the auricle. Full thickness defects can be reconstructed with local flaps. In this article, Davis flap was used to fill the upper third defects of the ear with some modifications. PATIENTS AND METHODS: Eight patients underwent reconstruction of full thickness auricular defects with Davis flaps from July 2012 to December 2014. The posterior surface of the flap and the raw area of conchal area were covered by full thickness graft taken from posterior surface of ear. RESULTS: All flaps survived. No congestion was noted. The donor sites and skin grafts healed uneventfully. CONCLUSION: Davis flap is a simple and reproducible tool for reconstruction of upper third of ear. PMID- 27274440 TI - Accuracy of computer-assisted implant placement with insertion templates. AB - OBJECTIVES: The purpose of this study was to assess the accuracy of computer assisted implant insertion based on computed tomography and template-guided implant placement. MATERIAL AND METHODS: A total of 246 implants were placed with the aid of 3D-based transfer templates in 181 consecutive partially edentulous patients. Five groups were formed on the basis of different implant systems, surgical protocols and guide sleeves. After virtual implant planning with the CoDiagnostiX Software, surgical guides were fabricated in a dental laboratory. After implant insertion, the actual implant position was registered intraoperatively and transferred to a model cast. Deviations between the preoperative plan and postoperative implant position were measured in a follow-up computed tomography of the patient's model casts and image fusion with the preoperative computed tomography. RESULTS: The median deviation between preoperative plan and postoperative implant position was 1.0 mm at the implant shoulder and 1.4 mm at the implant apex. The median angular deviation was 3.6o. There were significantly smaller angular deviations (P=0.000) and significantly lower deviations at the apex (P=0.008) in implants placed for a single-tooth restoration than in those placed at a free-end dental arch. The location of the implant, whether in the upper or lower jaw, did not significantly affect deviations. Increasing implant length had a significant negative influence on deviations from the planned implant position. There was only one significant difference between two out of the five implant systems used. CONCLUSION: The data of this clinical study demonstrate the accuracy and predictable implant placement when using laboratory-fabricated surgical guides based on computed tomography. PMID- 27274441 TI - Carbapenem-resistant Gram-negative bacteria - analysis of the data obtained through a mandatory reporting system in the Rhine-Main region, Germany, 2012 2015. AB - BACKGROUND: Multidrug-resistant Gram-negative bacteria (MRGN) and the infections they cause are a serious threat and a challenge to the healthcare system. This particularly applies to carbapenem-resistant Gram-negative bacteria (CRGN). Currently, the introduction of a nationwide mandatory notification system for CRGN in Germany is under consideration. Against this background, this paper presents an analysis of the mandatory reporting system for CRGN in effect since November 2011 in the federal state of Hesse (Germany). MATERIALS AND METHODS: All carbapenem-resistant Gram-negative bacteria and the detected carbapenemases reported to the public health department of the city of Frankfurt am Main, Hesse, Germany, on the basis of the mandatory notification system were analyzed. RESULTS: 827 CRGN cases were reported to the public health department of Frankfurt/Main between April 2012 and December 2015. The following bacterial species were reported: Pseudomonas spp. (n=268), Acinetobacter spp. (n=183), Klebsiella spp. (n=195), Enterobacter spp. (n=77), Escherichia coli (n=75) and others (n=29). Between 2012 and 2015, a reduction of the CRGN reports was noticed, mainly due to changes in the reporting of Pseudomonas spp. Between 2012 and 2015, the total number of notifications decreased slightly, although the number of reported CRGN in screening samples increased, thus giving no indication of a decreased testing frequency. For 10.5% of the patients, the place of residence was not Germany, 18.0% of the patients had previously stayed in hospitals abroad, often in countries with a high CRGN prevalence. CRGN bacteria were reported from all of Frankfurt's hospitals, and 3.9% were reported from out patient care facilities. Carbapenemases were detected and reported in 251 CRGN bacteria, including 73 OXA-48, 76 OXA-23, 56 NDM subtypes, and 21 KPC subtypes. There have been no major epidemiological signs of outbreak scenarios. DISCUSSION: CRGN bacteria are already widespread in patients from hospitals and out-patient care facilities. Clearly, infection control measurements should therefore not only include hospital patients but also those receiving out-patient care. Screening strategies focused on patients from foreign countries with high MRGN prevalence is not sufficient, as only 10.5% of MRGN patients resided in those countries, and only 18% of the patients had been previously treated in a foreign hospital. In a public health context, infection control measures should therefore encompass broader screening strategies. PMID- 27274443 TI - Impact of new water systems on healthcare-associated colonization or infection with Pseudomonas aeruginosa. AB - AIM: We aimed to study the impact of new water systems, which were less contaminated with P. aeruginosa, on the incidence of healthcare-associated P. aeruginosa cases (colonizations or infections) in care units that moved to a different building between 2005 and 2014. METHODS: Generalized Estimated Equations were used to compare the incidence of P. aeruginosa healthcare associated cases according to the building. RESULTS: Twenty-nine units moved during the study period and 2,759 cases occurred in these units. No difference was observed when the new building was compared with older buildings overall. CONCLUSION: Our results did not support our hypothesis of a positive association between water system contamination and the incidence of healthcare-associated P. aeruginosa cases. These results must be confirmed by linking results of water samples and patients' data. PMID- 27274444 TI - An All-Inside Repair for Full Radial Posterior Lateral Meniscus Tears. AB - There is controversy about the treatment for unstable full radial posterior lateral meniscus tears, particularly that involving the posterior root. Some surgeons have advocated repairing these types of meniscus tears using various techniques, but their methods are somewhat technical. We developed the technique for an all-inside repair for full radial posterior lateral meniscus tears using the Meniscal Viper (Arthrex, Naples, FL). A doubled thread is passed through 1 edge of the radial tear by the Meniscal Viper and is kept in place without tying the knot. The Meniscal Viper is used again to set a new thread, repeating the same procedure to another edge of the tear. At this step, 2 doubled threads are passed through each stump of the tear, and both a loop end and 2 free ends of each thread are located outside of the joint. Then, 2 doubled threads pass the third thread into its own loop, pulling it out. Finally, the third thread becomes the mattress suture over the radial tear site and is fastened by sliding knot techniques. This procedure makes it easy to strictly, smoothly, and less invasively shorten the gap by drawing each stump of the meniscus in the direction of the circumference. PMID- 27274445 TI - Minimally Invasive Anterior Semitendinosus Harvest: A Technique to Decrease Saphenous Nerve Injury. AB - Hamstring tendon harvest, especially semitendinosus harvest, has been widely used in anterior cruciate ligament reconstruction for many years. However, donor site morbidity has been described regarding the infrapatellar branch of the saphenous nerve. Minimally invasive anterior semitendinosus harvest is a simple, safe, reproducible, and elegant technique. A 2-cm vertical incision above the pes anserinus is performed 2 cm medial to the tibial anterior tubercle. The fascia superficialis is opened with a horizontal incision, and the gracilis is isolated using a retractor. The semitendinosus is grabbed with a probe, and the vincula are hooked one by one. The tendon is harvested with a closed stripper. The expansions are cut, and the tendon is detached from the bone with part of the periosteum. PMID- 27274442 TI - Surveillance of bloodstream infections in pediatric cancer centers - what have we learned and how do we move on? AB - Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients' safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined. PMID- 27274446 TI - All-Arthroscopic Ligamentum Teres Reconstruction With Graft Fixation at the Femoral Head-Neck Junction. AB - Ligamentum teres (LT) tears are increasingly being recognized as a source of pain and dysfunction in the hip. Although debridement for partial tears of the LT has long been established as the standard of care with good pain relief, reconstruction has been successfully performed in select patients to address concerns of persistent symptomatic instability. The current technique for femoral tunnel preparation carries the added morbidity of open dissection in the peritrochanteric space, an unnecessarily long tunnel with excessive bone removal, and a need for a very long graft due to distal fixation at the lateral femoral cortex. To address these shortcomings, we present a technique for arthroscopic femoral tunnel drilling at the level of the head-neck junction, allowing for an all-arthroscopic LT reconstruction. PMID- 27274447 TI - Fresh Osteochondral Allograft Transplantation for Treatment of Articular Cartilage Defects of the Knee. AB - Articular cartilage damage of the knee can cause severe morbidity. Owing to its avascular nature, articular cartilage has limited potential for self-healing and increased propensity to progress to osteoarthritis. Treatment of large, full thickness cartilage defects is still a challenge for orthopaedic surgeons but has recently achieved high success rates with the use of osteochondral allografts. This article details our technique of osteochondral allograft transplantation for the treatment of articular cartilage defects of the knee. PMID- 27274448 TI - Inside-Out Meniscal Repair: Medial and Lateral Approach. AB - Preservation of meniscal tissue has been proven to be the best approach in most cases of meniscal tears. Currently available techniques for treating a peripheral meniscal tear include inside-out, outside-in, and all-inside techniques. Each of these techniques present potential advantages and disadvantages. Despite technologic advances in all-inside devices, because of implant-related complications, cost concerns, and device availability, the inside-out technique is still the preferred method among many surgeons. Although the inside-out repair technique is considered more technically demanding and requires additional incisions, it has several advantages such as the possibility for an increased number of sutures, creating a stronger construct, and greater versatility in their placement. This article describes the inside-out meniscal repair technique with its corresponding posterolateral and posteromedial surgical approaches. PMID- 27274449 TI - Patellofemoral Joint Reconstruction for Patellar Instability: Medial Patellofemoral Ligament Reconstruction, Trochleoplasty, and Tibial Tubercle Osteotomy. AB - Recurrent patellar instability can be very debilitating and may require surgical intervention. A thorough workup must be completed in this subset of patients. Risk factors for recurrent instability include patella alta, trochlear dysplasia, an increased tibial tubercle-trochlear groove distance, and insufficiencies in the medial retinacular structures. Necessary treatment of these risk factors, once identified, should be addressed surgically. Patellofemoral reconstruction must be individually tailored to each patient's anatomy and may necessitate medial patellofemoral ligament reconstruction, tibial tubercle osteotomy, or trochleoplasty in any combination or as a standalone procedure. This article details our technique for surgical treatment of recurrent patellar instability with a medial patellofemoral ligament reconstruction, an open trochleoplasty, and a tibial tubercle osteotomy for patients with severe trochlear dysplasia, an increased tibial tubercle-trochlear groove distance, or patella alta. PMID- 27274450 TI - The Combined "Double-Pulley" Simple Knot Technique for Arthroscopic Transtendon Fixation of Partial Articular-Sided Tear of the Subscapularis Tendon. AB - Subscapularis tendon tears occur more frequently than previously suspected. Most subscapularis tendon tears are partial tears that have the potential to progress to complete tears. Repairs of partial tears of the tendon are performed to preserve normal shoulder function. This report describes a combined transtendon double-pulley and simple knot technique for repair of partial articular tears of the subscapularis tendon. This technique incorporates the advantages of transtendon repair, the double-pulley technique, and simple knot fixation. PMID- 27274451 TI - Surgical Dissection of the Anterolateral Ligament. AB - Recent investigations into the structure and function of the anterolateral ligament (ALL) have resulted in renewed interest in the role of the lateral extra articular structures in rotational control of the knee. With increased focus on the ALL, debate about the anatomic characteristics, the functional role in knee stability, and even the existence of this lateral structure has ensued. This article describes our dissection method for the ALL. Through careful dissection and precise elevation of the iliotibial band, the ALL can be clearly identified as a distinct structure with an attachment near the lateral epicondyle on the femur and an insertion in a fan-like fashion onto the tibia, between the Gerdy tubercle and the fibular head. This investigation provides the surgeon with anatomic landmarks to use during surgical reconstruction of the ALL. PMID- 27274452 TI - Two-Stage Revision Anterior Cruciate Ligament Reconstruction: Bone Grafting Technique Using an Allograft Bone Matrix. AB - Outcomes of primary anterior cruciate ligament (ACL) reconstruction have been reported to be far superior to those of revision reconstruction. However, as the incidence of ACL reconstruction is rapidly increasing, so is the number of failures. The subsequent need for revision ACL reconstruction is estimated to occur in up to 13,000 patients each year in the United States. Revision ACL reconstruction can be performed in one or two stages. A two-stage approach is recommended in cases of improper placement of the original tunnels or in cases of unacceptable tunnel enlargement. The aim of this study was to describe the technique for allograft ACL tunnel bone grafting in patients requiring a two stage revision ACL reconstruction. PMID- 27274453 TI - The Role of Complete Suprapatellar Plicae. AB - Shelf syndrome mainly affects younger people, often athletes. Cases of complete suprapatellar plica syndrome are rare. Arthroscopic inspection is necessary to diagnose complete suprapatellar plicae. The patients' symptoms improve after removal of the plicae. Our technique is an easy, completely arthroscopic procedure that has yielded good clinical outcomes in patients who have complete suprapatellar plicae. Although cases of complete suprapatellar plica syndrome are rare, it should be considered in patients with moderate knee pain. PMID- 27274454 TI - Arthroscopic Conjoint Tendon Transfer: A Technique for Revision Anterior Shoulder Stabilization. AB - Revision anterior stabilization of the shoulder presents a challenge to the surgeon and carries a higher risk of recurrent dislocation than primary repair. The Latarjet procedure may be more reliable than revision soft-tissue repair but may not be indicated in patients without significant glenoid bone loss. We describe an arthroscopic technique of conjoint tendon transfer using a combination of suspensory and interference screw fixation for patients without significant glenoid bone loss (<15%). The arthroscopic approach to this procedure allows intra-articular visualization to assist in mobilization of the conjoint tendon, accurate bone tunnel placement, and subsequent labral repair. It avoids the additional steps of bone block preparation and the larger portals required for arthroscopic Latarjet techniques, in addition to eliminating potential complications due to coracoid bone block resorption. PMID- 27274455 TI - Anatomic Reconstruction of the Proximal Tibiofibular Joint. AB - Proximal tibiofibular joint (PTFJ) instability can be easily missed or confused for other, more common lateral knee pathologies such as meniscal tears, fibular collateral ligament injury, biceps femoris pathology, or iliotibial band syndrome. Because of this confusion, some authors believe that PTFJ instability is more common than initially appreciated. Patients with PTFJ subluxation may have no history of inciting trauma or injury, and it is not uncommon for these patients to have bilateral symptoms and generalized ligamentous laxity. Currently, the optimal surgical treatment for patients with chronic PTFJ instability is unknown. Historically, a variety of surgical treatments have been reported. Initially, joint arthrodesis and fibular head resection were recommended. More recently, temporary screw fixation, nonanatomic reconstruction with strips of the biceps femoris tendon or iliotibial band, and reconstruction with free hamstring autograft have been described. The purpose of this report is to present our surgical technique for treatment of chronic PTFJ instability using an anatomic reconstruction of the posterior ligamentous structures of the PTFJ with a semitendinosus autograft. PMID- 27274456 TI - Minimally Invasive Anterolateral Ligament Reconstruction in the Setting of Anterior Cruciate Ligament Injury. AB - Recent evidence on the anatomy, function, and biomechanical properties of the anterolateral ligament has led to the recognition of the importance of this structure in the rotational control of the knee. This article describes a technique that allows for minimally invasive anterolateral ligament reconstruction as a complement to most techniques of anterior cruciate ligament reconstruction. A gracilis tendon autograft is harvested and prepared in a double strand, inverted V-shaped graft. The graft is percutaneously placed through a femoral stab incision, and each strand is then passed deep to the iliotibial band, emerging through each tibial stab incision. After the femoral-end loop graft is fixed, the tibial fixation of each strand is performed in full extension for optimal isometry. PMID- 27274457 TI - Detection of phosphorylated Akt and MAPK in cell culture assays. AB - This article describes an immunocytochemistry (ICC) method for staining against phosphorylated forms of the kinases Akt (pAkt) and MAPK (pMAPK). Phosphorylation is induced upon their activation by a number stimuli including insulin and brain derived neurotrophic factor (BDNF), and is prerequisite for a number of cellular processes including cell proliferation and survival [1], [2], [3], [4], [5], [6]. ICC using antibodies raised against specific phosphorylation sites allows cell type specific and subcellular monitoring of kinase activation. Here, we test how four different antibodies against pAkt and pMAPK, respectively perform in different cell types following insulin or BDNF stimulation using different protocol conditions. We find that phospho-specific-antibodies generally perform better when using Triton X-100 as a permeabilization agent compared to Saponin. In addition, two antibodies against pAkt and two against pMAPK gave a clear increase in signal in cells stimulated with insulin or BDNF compared to the signal obtained in unstimulated cells. These antibodies also performed well when tested with western blotting. Our results illustrate that both the choice of antibody as well as protocol details are critical parameters for successful detection of phosphorylated forms of kinases by ICC. This article includes: *A protocol for subcellular detection of phosphorylated Akt and MAPK.*Validation of 8 antibodies by immunocytochemistry.*Confirmation by western blotting. PMID- 27274458 TI - Scrap tyre recycling process with molten zinc as direct heat transfer and solids separation fluid: A new reactor concept. AB - Every year about 1.5 billion tyres are discarded worldwide representing a large amount of solid waste, but also a largely untapped source of raw materials. The objective of the method was to prove the concept of a novel scrap tyre recycling process which uses molten zinc as the direct heat transfer fluid and, simultaneously, uses this media to separate the solids products (i.e. steel and rCB) in a sink-float separation at an operating temperature of 450-470 degrees C. This methodology involved: *construction of the laboratory scale batch reactor,*separation of floating rCB from the zinc,*recovery of the steel from the bottom of the reactor following pyrolysis. PMID- 27274459 TI - A review of the effect of swim training and nutrition on bone mineral density in female athletes. AB - PURPOSE: The present paper reviews the physiological adaptation to swim training and dietary supplementation relating to bone mineral density (BMD) in female swimmers. Swim training still seems to have conflicting effects on bone health maintenance in athletes. METHODS: This review article focuses on swim training combined with dietary supplementation with respect to BMD in female athletes. RESULTS: Upon review of previous studies, it became obvious that the majority of studies did not collect physical activity data on the swimmers outside of their swimming activities. These activities may have some influence on the BMD of swimmers and therefore, future studies need to examine additional physical activity history data as well as swim training. This additional information may help to explain why swimmers' BMD tends to be lower than the BMD of control individuals in many studies. Moreover, dietary supplementation such as calcium, magnesium, and vitamin D also affect bone health in swimmers, and it is extremely important to evaluate BMD in the context of dietary supplementation. CONCLUSION: A review of the literature suggests that exercise intervention studies, including longitudinal and randomized control trials, need to attempt to introduce various exercise programs to female swimmers in order to determine the optimal exercise prescription for bone health. PMID- 27274462 TI - Preparation and characterization of fine powdered whole soybean curd. AB - PURPOSE: Efficacy and comparative characteristics of fine powdered whole soybean curd. METHODS: Ground dried soybean to a fine powder (700 mesh) containing bean components in its entirety, and then produced whole soybean curd. Analysed its nutritive components, bioactive substances, antioxidant activities and texture compared with pressed soybean curd. RESULTS: Compared with pressed soybean curd, the nutrients and isoflavone in whole soybean curd were slightly decreased, but antioxidant activities, dietary fibers and moisture content were increased. Also, the yield rate of the total process was improved 1.9 times. CONCLUSION: Fine powdered whole bean curd has antioxidant effects, contains dietary fiber and possesses soft characteristics, hence has development potential in the diet market and as food for patients. PMID- 27274460 TI - Resistance training inhibits the elevation of skeletal muscle derived-BDNF level concomitant with improvement of muscle strength in zucker diabetic rat. AB - PURPOSE: In the present study, we investigated the effects of 8 weeks of progressive resistance training on the level of skeletal muscle derived BDNF as well as glucose intolerance in Zucker diabetic rats. METHODS: Six week-old male Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were randomly divided into 3 groups: sedentary ZLC (ZLC-Con), sedentary ZDF (ZDF-Con), and exercised ZDF (ZDF-Ex). Progressive resistance training using a ladder and tail weights was performed for 8 weeks (3 days/week). RESULTS: After 8 weeks of resistance training, substantial reduction in body weight was observed in ZDF-Ex compared to ZDF-Con. Though the skeletal muscle volume did not change, grip strength grip strength was significantly higher in ZDF-Ex compared to ZDF-Con. In the soleus, the level of BDNF was increased in ZDF-Con, but was significantly decreased (p<0.05) in ZDF-Ex, showing a training effect. Moreover, we found that there was a negative correlation (r=-0.657; p=0.004) between grip strength and BDNF level whereas there was a positive correlation (r=0.612; p=0.008) between plasma glucose level and BDNF level in skeletal muscle. CONCLUSION: Based upon our results, we demonstrated that resistance training inhibited the elevation of skeletal muscle derived-BDNF expression concomitant with the improvement of muscle strength in zucker diabetic rats. In addition, muscle-derived BDNF might be a potential mediator for the preventive effect of resistance training on the progress of type 2 diabetes. PMID- 27274461 TI - Effect of high-intensity exercise and high-fat diet on lipid metabolism in the liver of rats. AB - PURPOSE: This study investigated the effects of high-intensity exercise (Ex) and high dietary fat intake on lipid metabolism in the liver of rats. METHODS: Male Sprague-Dawley rats were randomly assigned to one of the four groups (n=10 per group) that were maintained on a normal diet (ND) or high-fat diet (HFD) consisting of 30% fat (w/w), with or without exercise on a treadmill at 30 m/min and 8% grade) for 4 weeks (i.e., ND, ND+Ex, HFD, and HFD+Ex groups). RESULTS: Body weight (p<.001), total plasma cholesterol (TC) (p<.001), triglyceride (TG) (p<.05), and liver TG levels (p<.05) were increased in the HFD group relative to the ND groups, and serum glucose (p<.05), insulin (p<.05), homeostatic model assessment of insulin resistance (HOMA-IR) (p<.01), and liver TG levels (p<.01) were also higher in the HFD group compared to the ND+Ex group. Plasma free fatty acid was elevated in the HFD+Ex group compared to the HFD group (p<.01). With the exception of acetyl coenzyme A carboxylase, the expression of lipid metabolism related genes in the liver was altered in the Ex groups compared to the control group (p<.05), with genes involved in lipolysis specifically up regulated in the HFD+Ex group compared to the other groups. CONCLUSION: Vigorous exercise may increase glucose utilization and fat oxidation by activating genes in the liver that are associated with lipid metabolism compared to that in animals consuming a HFD without exercise. Therefore, high intensity exercise can be considered to counter the adverse effects of high dietary fat intake. PMID- 27274463 TI - Serum levels of appetite-regulating hormones and pro-inflammatory cytokines are ameliorated by a CLA diet and endurance exercise in rats fed a high-fat diet. AB - PURPOSE: This study examined whether conjugated linoleic acid (CLA) supplementation and endurance exercise affect appetite-regulating hormones and pro-inflammatory cytokines in rats. METHODS: Seven-week-old male Sprague-Dawley rats were divided randomly into the high-fat diet sedentary group (HS, n=8), the 1.0% CLA supplemented high-fat diet sedentary group (CS, n=8), and the 1.0% CLA supplemented high-fat diet exercise group (CE, n=8). Rats in the CE group swam 60 min/day, 5 days/week for 4 weeks. RESULTS: Leptin and insulin levels in the CS and CE groups were significantly lower than those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels decreased significantly in the CE compared to those in the CS group. Interleukin (IL)-1beta (p<0.001) and IL 6 (p<0.01) levels in the CS and CE groups decreased significantly compared to those in the HS group. Leptin (IL-1beta: r=0.835, p<0.001), IL-6 (r=0.607, p<0.05), insulin (IL-1beta: r=0.797, p<0.01), and IL-6 (r=0.827, p<0.01) levels were positively related with pro-inflammatory cytokine levels. CONCLUSION: Endurance exercise may play an important role during CLA supplementation of rats on a high-fat diet. PMID- 27274464 TI - Six week swimming followed by acute uptakes of ginsenoside Rg1 may affect aerobic capacity of SD rats. AB - PURPOSE: The purpose of this study is to examine the effects of six-weeks of endurance swim training and short-term intake of Rg1 on the expression of related proteins as well as improvement of aerobic exercise capacity in 8-week-old male SD rats. METHODS: The groups were divided into placebo (NP, n=6), Rg1 (NRG, n=6), exercise+placebo (EP, n=7), and exercise+Rg1 (ERG, n=7). On completion of the 6 week swimming exercise, Rg1-intake groups were treated with acute uptakes (3 times within 24hrs) of Rg1. After the treatment, all groups were subjected to a swim to exhaustion test, and then the mass of muscle tissue, mRNA expression level and activity of citrate synthase (CS) were analyzed on plantaris. RESULTS: There were no differences in the effect of 6-week swimming exercise and short term intake of Rg1 on body weight and muscle mass between groups. Although the CS mRNA expression was elevated in the exercise group and combined treatment group, there was no significant difference in CS activity. Acute uptakes of Rg1 did not affect swimming time to exhaustion, but it was increased by 235% and 314% by the 6-weeks of exercise and combined treatment of exercise and Rg1, respectively, which suggests that the combined treatment increased the effect on the capacity of aerobic exercise. CONCLUSION: Based on these results, it was confirmed that even a short-term treatment of Rg1 can give an additive effect for improvement of exercise function, and additional studies are needed for the mechanisms and modes of its working. PMID- 27274465 TI - Conversion Total Knee Arthroplasty after Failed High Tibial Osteotomy. AB - Clinical results of high tibial osteotomy (HTO) deteriorate over time despite the initial satisfactory results. Several knees may require a conversion to total knee arthroplasty (TKA) because of failure such as the progression of degenerative osteoarthritis and the loss of the correction angle. It is important to know the long-term survival rate and common reason of failure in HTO to inform patients of postoperative expectations before surgery and to prevent surgical errors during surgery. In addition, it has been reported that clinical and radiological results, revision rate, and complication rate were poorer than those in patients without a previous HTO. There are few review articles that describe why conversion TKA after HTO is surgically difficult and the results are poor. Surgeons have to avoid the various complications and surgical errors in this specific situation. We would like to present the considering factors and technical difficulties during conversion TKA after HTO with a review of the literature. We could conclude through the review that the correction of deformity, lower amount of tibial bone resection, and sufficient polyethylene insert thickness, restoration of the joint line height, and adequate ligament balancing can be helpful in overcoming the technical challenges encountered during TKA following HTO. PMID- 27274466 TI - The Efficacy of Medial Patellofemoral Ligament Reconstruction Combined with Tibial Tuberosity Transfer in the Treatment of Patellofemoral Instability. AB - A systematic review of the literature was undertaken to evaluate the efficacy of medial patellofemoral ligament (MPFL) reconstruction combined with tibial tuberosity transfer (TTT) in the treatment of patellofemoral instability. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic search was carried out to identify and review the published literature pertinent to MFPL reconstruction combined with TTT. Relevant studies were critically appraised with narrative data synthesis. Studies that met the eligibility criteria were suitable for appraisal and consisted of case series and therapeutic series (levels IV & III). All studies had inherent variations in outcomes reporting and limited follow-up. Combined treatment offers restoration of normal anatomy, thus adding clinical value to the currently recommended anatomic approach to MPFL reconstruction. Nevertheless, the current body of evidence does not determine the threshold at which patellofemoral axis requires the need for adjunctive distal realignment as opposed to MPFL reconstruction alone. This review highlighted numerous recurring limitations in the conduct and presentation of the studies, which inadvertently mitigated the interpretation of their results. Future priority should be awarded to larger randomised controlled trials utilising validated patient reported outcome measures. PMID- 27274467 TI - In vivo Kinematics of the Knee after a Posterior Cruciate-Substituting Total Knee Arthroplasty: A Comparison between Caucasian and South Korean Patients. AB - PURPOSE: This study compared in vivo kinematic differences between Caucasian and South Korean patients after a posterior-substituting total knee arthroplasty (PS TKA). MATERIALS AND METHODS: In vivo motions of 9 Caucasian and 13 South Korean knees with a PS-TKA during weight bearing single leg lunge were determined using a dual fluoroscopic imaging technique. Normalized tibiofemoral condylar motions and articular contact locations were analyzed. RESULTS: Femoral condylar motions of the two groups showed a similar trend in anteroposterior translation, but the South Korean patients were more anteriorly positioned than the Caucasian patients at low flexion and maximal flexion angles in both medial and lateral compartments (p<0.05). Mediolateral femoral condyle translations were similar between the two groups. For tibiofemoral articular contact kinematics, the South Korean patients had significantly more anterior contact locations at the medial compartment at low flexion angles, and more lateral contact locations at the lateral compartment at 0 degrees and 90 degrees flexion compared to the Caucasian patients (p<0.05). The South Korean patients had significantly larger distances between the medial and lateral contact locations at 60 degrees and 90 degrees flexion compared to the Caucasian patients (p<0.05). CONCLUSIONS: The study revealed that while the Caucasian and South Korean knees had similar femoral condylar motions, after PS-TKA the South Korean patients showed different articular contact point kinematics compared to the Caucasian patients. PMID- 27274469 TI - Comparison of Difference in Hematologic and Hemodynamic Outcomes between Primary Total Knee Arthroplasty and Revision of Infected Total Knee Arthroplasty. AB - PURPOSE: This study is to identify preoperative cautions for revision of infected total knee arthroplasty (TKA) by understanding the differences in hematologic and hemodynamic changes between primary TKA and revision of infected TKA. MATERIALS AND METHODS: The study included 40 patients in each of the two groups: one group with patients who underwent TKA and the other group with patients who underwent revision of infected TKA. All patients matched for age and body mass index. The following data were compared between the groups: changes in blood pressure, variations in hemoglobin level, amount of postoperative blood loss and transfused blood, incidence of blood transfusion, white blood cell (WBC) count, albumin level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and liver enzyme level. RESULTS: The hemoglobin levels, transfusion rate, and the amount of blood loss were significantly higher in the revision group (p=0.012). In both groups, CRP reached the highest level on the 3rd postoperative day but it was normalized 2 weeks postoperatively; however, the revision TKA group showed a greater tendency to normalization (p=0.029). There were significant differences between the groups in ESR, WBC, blood pressure, and changes in liver enzyme levels. CONCLUSIONS: Revision of infected TKA results in greater hemodynamic variations than primary TKA. Therefore, more efforts should be made to identify pre- and postoperative hemodynamic changes and hematologic status. PMID- 27274468 TI - Active Flexion in Weight Bearing Better Correlates with Functional Outcomes of Total Knee Arthroplasty than Passive Flexion. AB - PURPOSE: Correlations between maximum flexion and functional outcomes in total knee arthroplasty (TKA) patients are reportedly weak. We investigated whether there are differences between passive maximum flexion in nonweight bearing and other types of maximum flexion and whether the type of maximum flexion correlates with functional outcomes. MATERIALS AND METHODS: A total of 210 patients (359 knees) underwent preoperative evaluation and postoperative follow-up evaluations (6, 12, and 24 months) for the assessment of clinical outcomes including maximum knee flexion. Maximum flexion was measured under five conditions: passive nonweight bearing, passive weight bearing, active nonweight bearing, and active weight bearing with or without arm support. Data were analyzed for relationships between passive maximum flexion in nonweight bearing by Pearson correlation analyses, and a variance comparison between measurement techniques via paired t test. RESULTS: We observed substantial differences between passive maximum flexion in nonweight bearing and the other four maximum flexion types. At all time points, passive maximum flexion in nonweight bearing correlated poorly with active maximum flexion in weight bearing with or without arm support. Active maximum flexion in weight bearing better correlated with functional outcomes than the other maximum flexion types. CONCLUSIONS: Our study suggests active maximum flexion in weight bearing should be reported together with passive maximum flexion in nonweight bearing in research on the knee motion arc after TKA. PMID- 27274470 TI - Posterior Shift of Contact Point between Femoral Component and Polyethylene in the LCS Rotating Platform Implant under Weight Bearing Condition. AB - PURPOSE: To analyze the contact mechanics of the femoral component and polyethylene of the Low Contact Stress rotating platform (LCS-RP) in nonweight bearing and weight bearing conditions using full flexion lateral radiographs. MATERIALS AND METHODS: From May 2009 to December 2013, 58 knees in 41 patients diagnosed with osteoarthritis and treated with total knee arthroplasty (TKA) were included in this study. TKA was performed using an LCS-RP knee prosthesis. Full flexion lateral radiographs in both weight bearing and nonweight bearing condition were taken at least one month postoperatively (average, 28.8 months). Translation of femoral component was determined by the contact point between the femoral component and polyethylene. Maximum flexion was measured as the angle between the lines drawn at the midpoint of the femur and tibia. RESULTS: Posterior shift of the contact point in LCS-RP TKA was observed under weight bearing condition, which resulted in deeper flexion compared to LCS-RP TKA under nonweight bearing condition. CONCLUSIONS: In the LCS-RP TKA, the contact point between the femoral component and polyethylene moved posteriorly under weight bearing condition, and the joint was more congruent and maximum flexion increased with weight bearing. PMID- 27274471 TI - Patterns and Influencing Factors of Medial Meniscus Tears in Varus Knee Osteoarthritis. AB - PURPOSE: To investigate the patterns of medial meniscus (MM) tears in patients with varus knee osteoarthritis who underwent total knee arthroplasty and analyze the factors that could affect MM tears. MATERIALS AND METHODS: The patients (365 knees, 268 patients) were classified into three groups; group I with MM posterior horn (PH) tear only; group II with MM root tear only; and group III with MMPH plus root tear. The following factors were evaluated: age, gender, body mass index, varus deviation of the mechanical axis, medial proximal tibial angle, posterior tibial slope (PTS), and anterior cruciate ligament (ACL) integrity (normal, degeneration, and tear or absence). RESULTS: MM tears were identified in all knees. The patterns of the combined MMPH tears in group III were less complex than those in group I. Varus deviation and PTS were significantly greater in group III than groups I and II. In group III, there were significantly more cases of ACL tear or absence than groups I and II. The others showed no differences among three groups. CONCLUSIONS: Severe varus knee osteoarthritis was always accompanied by MM tears. Risk factors for MMPH plus root tears were severe varus deformity, great PTS, and ACL tear or absence. PMID- 27274472 TI - The Optimal Suture Site for the Repair of Posterior Horn Root Tears: Biomechanical Evaluation of Pullout Strength in Porcine Menisci. AB - PURPOSE: There are few studies on biomechanical evaluation of suture points in repair of root tears. The purpose of this study was to determine the point of greatest pullout strength for root tear repair. MATERIALS AND METHODS: A total of 120 fresh porcine medial menisci were obtained. The red-red and red-white zones of the meniscus were divided by two lines designated as lines A and B (groups A and B). Groups A and B were further divided into three groups each by dividing lines A and B into three points: 3, 5, and 7 mm from the meniscal ligament root insertion. Vertical meniscal repair was performed on each point. The pullout failure strength was tested using a biaxial servohydraulic testing machine. RESULTS: The average maximal load at failure was significantly greater in group A than group B (87.65 vs. 62.93; p<0.001) The average length at maximal load failure was greater in group A than group B (4.35 vs. 3.2; p<0.001). Among the subgroups of 3, 5, and 7 mm in both groups A and B, 7 mm showed the greatest maximal load (p<0.001). CONCLUSIONS: The pullout strength was statistically significantly greater in group A than group B and in the 7 mm subgroup than the 3 and 5 mm subgroups. Thus, the 7 mm subgroup in group A showed the greatest pullout strength. PMID- 27274473 TI - A Novel Medial Soft Tissue Release Method for Varus Deformity during Total Knee Arthroplasty: Femoral Origin Release of the Medial Collateral Ligament. AB - INTRODUCTION: Numerous methods of medial soft tissue release for severe varus deformity during total knee arthroplasty (TKA) have been reported. These include tibial stripping of the superficial medial collateral ligament (MCL), pie crusting technique, and medial epicondylar osteotomy. However, there are inherent disadvantages in these techniques. Authors hereby present a novel quantitative method: femoral origin release of the medial collateral ligament (FORM). SURGICAL TECHNIQUE: For medial tightness remaining even after the release of the deep MCL and semimembranosus, the FORM is initiated with identification of the femoral insertion area of the MCL with the knee in flexion. Starting from the most posterior part of the femoral insertion, one third of the MCL femoral insertion is released from its attachment. If necessary, further sequential medial release is performed. MATERIALS AND METHODS: Seventeen knees that underwent the FORM were evaluated for radiological and clinical outcomes. RESULTS: Regardless of the extent of the FORM, no knees showed residual valgus instability at 24 weeks after surgery. CONCLUSIONS: As the FORM is performed in a stepwise manner, fine adjustment during medial release might be beneficial to prevent inadvertent over release of the medial structures of the knee. PMID- 27274474 TI - Surgical Treatment of Neglected Traumatic Quadriceps Tendon Rupture with Knee Ankylosis. AB - Quadriceps tendon rupture is an uncommon injury. This disabling condition is the result of direct or indirect trauma. It requires surgical repair to avoid poor outcomes in cases of neglected or chronic rupture. In most acute cases, simple tendon suture or reinsertion is suitable for an extensor mechanism reconstruction of the knee joint. However, chronic lesions often require a tendon graft or flap reconstruction. We report a case of a 15-year-old male who was diagnosed with a chronic quadriceps rupture with a patellar superior pole fracture. We performed quadriceps reconstruction using tibialis anterior allograft tendon and additional screw fixation to reconstruct the extensor mechanism and recover knee joint range of motion to prevent a high-level functional restriction. The treatment was difficult and limited due to neglect for 9-months that led to ankylosis accompanied with nonunion of tibial fracture. Our surgical treatment using allograft tendon resulted in a very good outcome after 30 months of follow-up. PMID- 27274475 TI - Simultaneous Osteoperiosteal Autologous Iliac Crest Graft and Lateral Meniscus Allograft Transplantation for Osteochondral Lesion with Bony Defect and Lateral Discoid Meniscus Tear. AB - The optimal treatment for combined osteochondritis dissecans (OCD) with considerable bony defect of the lateral femoral condyle (LFC) and torn discoid lateral meniscus is unclear. We present a case of a 15-year-old female who was a gymnast and had a large OCD lesion in the LFC combined with deficiency of the lateral meniscus. The patient underwent the "one-step" technique of osteoperiosteal autologous iliac crest graft and lateral meniscus allograft transplantation after a failure of meniscectomy with repair at another hospital. Twenty-four months postoperatively, clinical results were significantly improved. Follow-up imaging tests and second-look arthroscopy showed well incorporated structured bone graft and fibrous cartilage regeneration as well as stabilized lateral meniscus allograft. She could return to her sport without any pain or swelling. This "one-step" surgical technique is worth considering as a joint salvage procedure for massive OCD lesions with torn discoid lateral meniscus. PMID- 27274476 TI - Snapping Pes Syndrome after Unicompartmental Knee Arthroplasty. AB - Snapping pes syndrome is defined as a snapping sensation in the medial knee caused by pes anserinus and rarely occurs. Snapping pes syndrome after unicompartmental knee arthroplasty (UKA) has not been reported yet. We experienced two cases with this syndrome after UKA. Conservative treatment was effective in one case, while surgical excision of the gracilis tendon was necessary to relieve painful snapping in the other case. The main cause of the first case might be posteromedial overhang of the tibial tray that reached up to 5 mm. The probable cause of the second case was posteromedial overhang of the mobile bearing. PMID- 27274477 TI - Subtrochanteric fractures of the femur: update. AB - Because of the anatomical peculiarities of the subtrochanteric region, treatment of fractures in this region remains challenging. The undeniable evolution of implants has not been accompanied by the expected decrease in the complication rate. The aim of this study was to discuss critical points in detail, such as preoperative planning, reduction tactics and the current scientific evidence concerning treatment of subtrochanteric fractures of the femur. PMID- 27274478 TI - Comparative study on three surgical techniques for intra-articular calcaneal fractures: open reduction with internal fixation using a plate, external fixation and minimally invasive surgery. AB - OBJECTIVE: To evaluate, compare and identify the surgical technique with best results for treating intra-articular calcaneal fractures, taking into account postoperative outcomes, complications and scoring in the Aofas questionnaire. METHODS: This was a retrospective study on 54 patients with fractures of the calcaneus who underwent surgery between 2002 and 2012 by means of the following techniques: (1) open reduction with extended L-shaped lateral incision and fixation with double-H plate of 3.5 mm; (2) open reduction with minimal incision lateral approach and percutaneous fixation with wires and screws; and (3) open reduction with minimal incision lateral approach and fixation with adjustable monoplanar external fixator. RESULTS: Patients treated using a lateral approach, with fixation using a plate had a mean Aofas score of 76 points; those treated through a minimal incision lateral approach with screw and wire fixation had a mean score of 71 points; and those treated through a minimal incision lateral approach with an external fixator had a mean score of 75 points. The three surgical techniques were shown to be effective for treating intra-articular calcaneal fractures, without any evidence that any of the techniques being superior. CONCLUSION: Intra-articular calcaneal fractures are complex and their treatment should be individualized based on patient characteristics, type of fracture and the surgeon's experience with the surgical technique chosen. PMID- 27274479 TI - Osteosynthesis of mallet finger using plate and screws: evaluation of 25 patients. AB - OBJECTIVES: To evaluate the results from surgical treatment of patients with mallet finger injury using a hook plate and screw. METHODS: Twenty-five patients (19 males and six females) between the ages of 20 and 35 years were analyzed between May 2008 and December 2012. They were evaluated in accordance with Crawford's criteria and the mean follow-up was 18 months. RESULTS: The results from 10 patients (40%) were excellent and from 15 (60%), good. Twenty-one patients (84%) reported no pain, 18 months after the operation. There was no limitation to range of motion in 14 cases (56%), limitation of extension in seven (28%) and limitation of flexion in four (16%). CONCLUSION: Surgical treatment by means of open reduction and internal fixation using a hook plate and screw proved to be an excellent option for treating mallet finger fractures and was considered to be a safe and effective method. PMID- 27274481 TI - Anthropometric study of the knee and its correlation with the size of three implants available for arthroplasty. AB - OBJECTIVE: To define the anthropometric profile of the knee in a Brazilian population with gonarthrosis using intraoperative measurements; and to evaluate the compatibility of three implants available for total knee arthroplasty. METHODS: Morphometric data were collected prospectively from 117 subjects with gonarthrosis. Six dimensions in the distal femur and two in the proximal tibia were documented in 118 knees while performing total arthroplasty. These data were compared with the dimensions of three implants available for total knee arthroplasty. RESULTS: The statistical analysis showed that more than a quarter of the patients presented an unsatisfactory relationship between the knee and prosthesis. CONCLUSION: The implants evaluated need to be adjusted to better fit Brazilian patients. PMID- 27274480 TI - Transtibial technique versus two incisions in anterior cruciate ligament reconstruction: tunnel positioning, isometricity and functional evaluation. AB - OBJECTIVE: To compare the transtibial and two-incision techniques for anterior cruciate ligament (ACL) reconstruction using a single band. METHODS: A prospective and randomized study was conducted in blocks. Patients underwent ACL reconstruction by means of two techniques: transtibial (group 1: 20 patients) or two incisions (group 2: 20 patients). The radiographic positioning of the tunnel, inclination of the graft, graft isometricity and functional results (IKDC and Lysholm) were evaluated. RESULTS: The positioning of the femoral tunnel on the anteroposterior radiograph, expressed as a mean percentage relative to the medial border of the tibial plateau, was 54.6% in group 1 and 60.8% in group 2 (p < 0.05). The positioning of the femoral tunnel on the lateral radiograph, expressed as a mean percentage relative to the anterior border of Blumensaat's line, was 68.4% in group 1 and 58% in group 2 (p < 0.05). The mean inclination of the graft was 19 degrees in group 1 and 27.2 degrees in group 2 (p < 0.05). The mean graft isometricity was 0.96 mm in group 1 and 1.33 mm in group 2 (p > 0.05). Group 2 had better results from the pivot-shift maneuver (p < 0.05). CONCLUSION: The technique of two incisions allowed positioning of the femoral tunnel that was more lateralized and anteriorized, such that the graft was more inclined and there was a clinically better result from the pivot-shift maneuver. There was no difference in isometricity and no final functional result over the short follow up time evaluated. PMID- 27274482 TI - Reconstruction of the medial patellofemoral ligament by means of the anatomical double-bundle technique using metal anchors. AB - OBJECTIVE: To evaluate double-bundle reconstruction of the medial patellofemoral ligament (MPFL) using a graft from the semitendinosus tendon and fixation with metal anchors over the medium term. METHODS: This was a prospective cross sectional study. After approval from the research ethics committee, 31 patients with patellofemoral instability who underwent MPFL reconstruction by means of the anatomical double-bundle technique, with fixation using metal anchors, were analyzed between May 2010 and January 2015. To evaluate the effectiveness of the MPFL reconstruction surgery, the Kujala scale and the Tegner-Lysholm score were assessed before the procedure and one year afterwards, along with clinical data such as pain levels, range of motion and J sign. The data were tabulated in the Excel((r)) software and were analyzed using the SPSS Statistics((r)) software, version 21. The statistical analysis was performed using the Wilcoxon T test and the McNemar test. RESULTS: The mean preoperative score from the Kujala test was 45.64 +/- 1.24 and the postoperative score was 94.03 +/- 0.79 (p < 0.001). The preoperative Tegner-Lysholm score was 40.51 +/- 1.61 and the postoperative score was 91.64 +/- 0.79 (p < 0.001). The preoperative range of motion was 125.96 +/- 2.11 and the postoperative range was 138.38 +/- 1.49 (p < 0.05). CONCLUSION: MPFL reconstruction by means of the anatomical double-bundle technique is easily reproducible, without episodes of recurrence, with satisfactory results regarding restoration of stability and function of the patellofemoral joint. PMID- 27274483 TI - Rotator cuff injuries and factors associated with reoperation. AB - OBJECTIVE: To evaluate the prevalence of rotator cuff tears and describe the profile of reoperated patients, causes of repeated tendon tears, tear evolution and range of times between surgical procedures. METHOD: This was a cross sectional study involving 604 surgical procedures performed at two regional referral hospitals between January 2006 and December 2012. After approval by the ethics committee, data describing the patients' epidemiological profile were gathered at a single time, using Cofield's classification to measure the extent of the tears, all of which underwent arthroscopic surgery. The data were entered into Epi Info 3.5.3 and were analyzed using SPSS version 18.0. RESULTS: Among the 604 surgical procedures, females were affected in more cases (351; 58.1%). When the dominant limb was the right limb, it was affected in 90% of the cases (p < 0.05). The supraspinatus tendon was affected in 574 cases (95%) and the tears were of medium size in 300 cases (49.7%). Eighteen reoperations were performed (2.98%) and the upper right limb was the most affected (66.6%). The cause was non traumatic in 12 patients. The repeated tears were mostly smaller (44%), and the length of time between the two surgical procedures ranged from 6 to 298 weeks. CONCLUSION: Female gender, smaller extent in the second procedure and non traumatic cause were found in most of the cases analyzed. PMID- 27274484 TI - Direct repair of chronic distal biceps tendon tears. AB - OBJECTIVE: To present the results from direct tendon repair using EndoButton and interference screws in patients with lesions of the distal biceps that had evolved over a period of more than 28 days. METHODS: Between January 2012 and November 2013, eleven patients (all male) with a torn distal biceps and a time interval between injury and surgery of more than 28 days were evaluated. The patients' mean age was 46 years and the most common mechanism of injury was eccentric loading with the elbow flexed and supinated. RESULTS: A subjective analysis on pain and function was conducted using a visual analog scale of pain (VAS) and the Mayo Elbow Performance Score (MEPS), before and after surgery. The VAS showed a decrease of 5 points to 0.8 points on average. The MEPS improved from 69.3 points before the operation to 97.5 points afterwards. The mean flexion was 133.1 degrees on the operated side, versus 134.3 degrees . The mean extension was -2.5 degrees and 0 degrees (operated side versus non-operated). Supination was 88.2 degrees versus 89.5 degrees and pronation was 82.5 degrees versus 84.1 degrees , comparing the operated side versus the non-operated side. Flexion and supination strengths were evaluated with the aid of a dynamometer, and the mean flexion and supination strengths were found to be respectively 78.57% and 89.65% of the strength of the non-operated limb. CONCLUSION: Use of the technique of direct tendon repair using EndoButton and interference screws was shown to be a safe and effective alternative for repairing chronic lesions of the distal biceps. PMID- 27274485 TI - Treatment of congenital clubfoot using Ponseti method. AB - OBJECTIVE: To quantitatively and qualitatively analyze the results from treatment of congenital clubfoot with a mean follow-up of 4.6 years. METHODS: 26 patients who underwent treatment by means of the Ponseti method were analyzed (total of 39 feet). The mean age at the start of the treatment was 5.65 months. The mean length of the follow-up subsequent to tenotomy of the Achilles tendon was 4.6 years. Patients with secondary clubfoot were excluded. Epidemiological data, radiographic measurements on the Kite angle and data from a satisfaction questionnaire and the Laaveg questionnaire were analyzed. RESULTS: Among the 26 patients treated, one presented recurrence of the deformity and had to return to the beginning of the treatment. The mean score from the questionnaire and physical examination was 89.76 points, and this result was considered good. 99% of the patients responded that their feet never hurt or hurt only upon great activity; 88% said that their feet did not limit their activities; and 96% said that they were very satisfied or satisfied with the results from the treatment. The mean Kite angle in anteroposterior view was 28.14 degrees and it was 26.11 degrees in lateral view. CONCLUSION: Treatment for idiopathic congenital clubfoot by means of the Ponseti method brings better results together with less soft-tissue injury, thus confirming the effectiveness and good reproducibility of this method. PMID- 27274486 TI - Obstetric paralysis: anterior arthroscopic release of the shoulder and transfer of the latissimus dorsi using a homologous graft. AB - OBJECTIVE: Description of a new surgical technique for treating the shoulders of patients with sequelae of obstetric paralysis. Preliminary analysis on the results obtained from this technique. METHODS: Five consecutive patients underwent the proposed surgical procedure, consisting of arthroscopic anterior joint release followed by transfer of the latissimus dorsi tendon (elongated and reinforced with a homologous tendon graft) to the posterosuperior portion of the greater tubercle, using a single deltopectoral approach. All the patients were reevaluated after a minimum postoperative period of twelve months. The functional assessment was based on the range of motion and the modified Mallet classification system. Statistical analyses were not possible because of the small sample. RESULTS: Overall, passive and active lateral rotations increased, while medial rotation decreased. The other movements (elevation, capacity to place a hand in the mouth and capacity to place a hand behind the neck) had less consistent evolution. The mean modified Mallet score improved by 4.2 points (from 11.4 to 15.6). CONCLUSION: The latissimus dorsi tendon can be transferred to the posterosuperior portion of the greater tubercle through a single deltopectoral approach when elongated and reinforced with a homologous tendinous graft. PMID- 27274488 TI - Postoperative comparison of the results from use of antibiotic prophylaxis for one and five days among patients undergoing lumbar arthrodesis. AB - OBJECTIVE: To compare the postoperative results from use of antibiotic prophylaxis for one and five days among patients undergoing lumbar arthrodesis at up to three levels. METHODS: Forty-three patients who all underwent lumbar arthrodesis due to degenerative disc disease at one, two or three levels were evaluated. They were divided randomly into two groups: one received antibiotic prophylaxis with cefalotin (1 g) and the other received the same antibiotic for five days. After the surgical intervention, the patients were evaluated at the time of hospital discharge, at the first return to the clinic (two weeks later) and 90 days after the date of the surgery with the surgical wound, with clinical examination of the surgical wound and laboratory tests on both groups. RESULTS: It was observed that among the patients in the group with one day of antibiotic prophylaxis, 28.6% presented complications in the surgical wound, while in the group with five days, 27.9% presented complications. CONCLUSION: This study demonstrates that a single dose of antibiotic prophylaxis is as effective as a regimen of multiple doses in lumbar arthrodesis surgery at up to three levels. Thus, the costs and risks of subjecting patients to hospitalization under a prolonged drug regimen are unjustifiable. PMID- 27274487 TI - Hip dislocation in cerebral palsy: evolution of the contralateral side after reconstructive surgery. AB - OBJECTIVE: To evaluate the progression of the contralateral hip after unilateral reconstruction of hip dislocation in patients classified as GMFCS IV-V; and to identify potential prognostic factors for their evolution. METHODS: This was a retrospective study on 17 patients with spastic cerebral palsy, who were classified on the GMFCS scale (Gross Motor Functional Classification System) as degrees IV and V, and who underwent unilateral reconstruction surgery to treat hip dislocation (adductor release, femoral varus osteotomy and acetabuloplasty). The minimum postoperative follow-up was 30 months. The clinical parameters evaluated were sex, age at time of surgery, length of follow-up after surgery and range of abduction. The treatment parameters were use/nonuse of femoral shortening, application of botulinum toxin and any previous muscle releases. The radiographic parameters were Reimer's extrusion index (REI), acetabular angle (AA) and the continuity of Shenton's line. RESULTS: Among the 17 patients evaluated, eight presented dislocation (group I) and nine did not (group II). Group I comprised three males and five females; group II comprised one male and eight females. The mean age at the time of surgery among the group I patients was 62 months and the mean follow-up was 62 months. In group II, these were 98 and 83 months, respectively. There was a trend in which patients of greater age did not evolve with contralateral dislocation. Among the nine patients with the combination of REI < 30% and AA < 25 degrees , only one presented dislocation during the follow-up. Contralateral subluxation occurred within the first two years after the surgery. CONCLUSION: Hips presenting REI < 30 degrees and AA < 25 degrees do not tend to evolve to subluxation and can be kept under observation. Preoperative clinical and radiographic measurements alone are not useful for indicating the natural evolution of non- operated hips. The critical period for subluxation is the first two years after surgery. PMID- 27274489 TI - Initial experience of use of an articulated external fixator in treating Legg Calve-Perthes disease by means of arthrodiastasis during the active phase of the disease. AB - OBJECTIVE: To present the preliminary results from treating patients with Legg Calve-Perthes Disease (LCPD) by means of hip arthrodiastasis using a monolateral external fixator applied to the hip and to succinctly describe the surgical technique used, in a prospective study. METHODS: Prospective study on 18 patients with LCPD who underwent surgical treatment by means of the hip arthrodiastasis technique using a monolateral external fixator. There were 13 male and five female patients of mean age 8.5 years, ranging from five to 13 years. All the patients presented unilateral hip impairment: nine on the right side and nine on the left. The results were evaluated at maturity using clinical and radiological criteria. RESULTS: All the patients evolved with improvement of joint mobility, and pain relief was achieved in 88.9% of them. Reossification of the femoral epiphysis occurred within the first three months of the treatment. The hips operated at the necrosis stage of the disease did not passed through the fragmentation stage, thus shortening the evolution of the disease. The results were 77.8% satisfactory and 22.2% unsatisfactory. CONCLUSION: Hip arthrodiastasis with a monolateral external fixator during the active phase of LCPD improved the degree of joint mobility. Use of the arthrodiastasis technique at the necrosis stage or at the fragmentation stage (active phase of the disease) presented satisfactory results from treatment of LCPD. PMID- 27274490 TI - Adverse effect of beta-tricalcium phosphate with zeta potential control in repairing critical defects in rats' calvaria. AB - OBJECTIVE: To evaluate whether a new biphasic cement composed of calcium sulfate and beta tricalcium phosphate with zeta potential control could induce or lead to bone neoformation in critical defects. METHODS: A critical defect of diameter 8 mm was made in the calvaria of forty male Wistar rats. In the Test Group (n = 20), the defects were filled with cement. In the Control Group (n = 20), the defect was not filled and only coagulum was present. The animals were sacrificed 7, 14, 21 and 42 days after the operation. Calvaria specimens were subjected to microtomography and were then prepared for histological analysis. The analyses included morphological assessment on the histopathology of the repair; comparative morphometric evaluation of the area of formation of bone trabeculae between the groups; and histochemical staining by means of tartrate-resistant phosphatase (TRAP) in order to identify osteoclasts. RESULTS: Microtomographic images of the defects filled by the cement did not show any decrease in area over the course of postoperative evolution. In the Test Group, the material continued to present a foreign-body response until the last observational periods. Histomorphological analysis showed that there were more significant groupings of giant cells in the Test Group and greater maturity of neoformed bone in the Control Group. Exogenous material was also present. Histomorphometric analysis showed that in the Control Group, the total area of bone neoformation was significantly greater (p = 0.009) and grew progressively. The giant cells presented a positive reaction to TRAP but no osteoclasts were observed. CONCLUSION: The ceramic cement did not induce or lead to bone neoformation from the microtomographic or histological point of view. PMID- 27274491 TI - Translation and transcultural adaptation of the Hip Fracture Recovery Score assessment tool. AB - OBJECTIVE: The Hip Function Recovery Score questionnaire is an instrument that was developed for evaluating the functional recovery of patients over 60 years of age who undergo surgical treatment due to hip fractures. The objective of this study was to make a thorough transcultural translation of this questionnaire, with adaptation to the individual and cultural traits of the Brazilian population. METHOD: This translation method consisted of initial translation, back translation, drafting of a consensual version and pretesting with comments invited. Subsequently, a final version was drawn up after making the necessary adjustments, without altering the semantics of the questions in the original text. RESULTS: The consensual version was applied to thirty patients over the age of 60 years who had undergone surgical treatment due to hip fractures. However, some difficulties in understanding some words and expressions were observed, and these were then replaced with terms that were more easily understood. After the final version had been drawn up, this was applied to the same patients and full understanding was achieved among some of them, without altering the semantics of the questions of the original text. CONCLUSION: The transcultural translation of the Hip Function Recovery Score will have an immediate impact on functional evaluations on patients over 60 years of age who underwent surgery due to hip fracture. It will subsequently be possible for other Brazilian scientific studies to use this questionnaire, which has been standardized and adapted to Brazilian culture, in order to make comparisons between results, thereby enriching Brazilian scientific production. PMID- 27274492 TI - Rare anatomical variation of the musculocutaneous nerve - case report. AB - The clinical and surgical importance of anatomical knowledge of the musculocutaneous nerve and its variations is due to the fact that one of the complications in many upper-limb surgical procedures involves injury to this nerve. During routine dissection of the right upper limb of a male cadaver, we observed an anatomical variation of this nerve. The musculocutaneous nerve originated in the lateral cord and continued laterally, passing under the coracobrachialis muscle and then continuing until its first branch to the biceps brachialis muscle. Just after this, it supplied another two branches, i.e. the lateral cutaneous nerve of the forearm and a branch to the brachialis muscle, and then it joined the median nerve. The median nerve followed the arm medially to the region of the cubital fossa and then gave rise to the anterior intermediate nerve of the forearm. The union between the musculocutaneous nerve and the median nerve occurred approximately at the midpoint of the arm and the median nerve. Given that either our example is not covered by the classifications found in the literature or that it fits into more than one variation proposed, without us finding something truly similar, we consider this variation to be rare. PMID- 27274493 TI - Solid variant of aneurysmal bone cist on the distal extremity of the radius in a child. AB - The solid variant of aneurismal bone cysts (ABC) is considered rare. It occurs with greater frequency in pediatric patients and in the tibia, femur, pelvis and humerus. We present a case of a metaphyseal lytic lesion on the distal extremity of the radius in a child whose radiograph was requested after low-energy trauma. The hypothesis of a pathological bone fracture secondary to an aneurysmal bone cyst was suggested. After biopsy, the child underwent intralesional excision without bone grafting and the histopathological findings were compatible with the solid variant of aneurysmal bone cyst. PMID- 27274494 TI - Stress fracture in acetabular roof due to motocross: case report. AB - One of the first steps to be taken in order to reduce sports injuries such as stress fractures is to have in-depth knowledge of the nature and extent of these pathological conditions. We present a case report of a stress fracture of the acetabular roof caused through motocross. This type of case is considered rare in the literature. The description of the clinical case is as follows. The patient was a 27-year-old male who started to have medical follow-up because of uncharacteristic pain in his left hip, which was concentrated mainly in the inguinal region of the left hip during motocross practice. After clinical investigation and complementary tests, he was diagnosed with a stress fracture of the acetabular roof. PMID- 27274495 TI - Reconstruction of chronic patellar tendon rupture using graft from contralateral patella graft together with reinforcement from flexor tendons. Case report. AB - Chronic patellar tendon rupture is a rare disabling injury that is technically difficult to repair. The true prevalence of this injury is unknown. Delayed reconstruction of chronic patellar tendon rupture has yielded suboptimal clinical and functional results. Many different surgical methods for reconstruction of chronic patellar tendon injury have been reported. In this report, we present a case with chronic patellar tendon injury that was addressed using a technique that had not previously been described in the literature, through combining procedures that had been described separately. The reconstruction method presented in this article has the advantages of being easy and reproducible, without a requirement of allografts. PMID- 27274496 TI - Prevalence and characteristics of gastroesophageal reflux in children with otitis media in Isfahan, Iran. AB - BACKGROUND: Otitis media (OM) is the most common cause of childhood hearing loss and reason to visit the pediatrician. Furthermore, gastroesophageal reflux (GER) has been associated with a variety of upper aerodigestive tract symptoms or diseases, such as sinusitis, laryngitis, and otits. The objective of the present study was to determine the frequency of GER in children, aged 3 months to 7 years, with OM. MATERIALS AND METHODS: This retrospective case-control study was conducted on 50 children with OM and 50 healthy children. Presence of GER as the main variables was diagnosed by clinical examination in all studied children using the questionnaires with 2 age-stratified versions of the pediatric GER disease symptoms for children 2 years old and younger, and children 3-7 years old. RESULTS: The prevalence of GER in children with OM and controls was 58% and 22% respectively (P = 0.0005). The frequency of irritability, congestion, and feeding complex in children with OM were significantly more than in control groups. Among children with recurrent acute OM (AOM), and chronic serous OM (CSOM) the prevalence of GER was significantly more than controls (61.1%, vs. 22% for AOM, P = 0.004, and 72.7% vs. 22%, P= 0.003). In children with AOM, regurgitation, vomiting, irritability and congestion were significantly higher than controls included. In children with CSOM, regurgitation, vomiting, and congestion were significantly higher than controls. CONCLUSION: Results show a significant association between GER and OM, AOM and CSOM in children with OM compares to healthy children. This shows that looking for GER in children with OM may help improving treatments outcomes. PMID- 27274497 TI - Predictors of all-cause and cardiovascular-specific mortality in type 2 diabetes: A competing risk modeling of an Iranian population. AB - BACKGROUND: In Asian population, diabetes mellitus is increasing and has become an important health problem in recent decades. In Iran, cardiovascular disease (CVD) accounts for nearly 46% of the total costs spent for diabetes-associated diseases. Because individuals with diabetes have highly increased CVD risk compared with normal individuals, it is important to diagnosis factors that may increase CVD risk in diabetic patients. The study objective was to identify predictors associated with CVD mortality in patients with type 2 diabetes (T2D) and to develop a prediction model for cardiovascular (CV)-death using a competing risk approach. MATERIALS AND METHODS: The study population consisted of 2638 T2D (male = 1110, female = 1528) patients aged >=35 years attending from Endocrine and Metabolism Research Center in Isfahan for a mean follow-up period of 12 years; predictors for different cause of death were evaluated using cause specific Cox proportional and subdistribution hazards models. RESULTS: Based on competing modeling, the increase in blood pressure (BP) (spontaneously hypertensive rats [SHR]: 1.64), cholesterol (SHR: 1.55), and duration of diabetes (SHR: 2.03) were associated with CVD-death. Also, the increase in BP (SHR: 1.85), fasting blood sugar (SHR: 2.94), and duration of diabetes (SHR: 1.68) were associated with other death (consist of cerebrovascular accidents, cancer, infection, and diabetic nephropathy). CONCLUSIONS: This finding suggests that more attention should be paid to the management of CV risk in type 2 diabetic patients with high cholesterol, high BP, and long diabetes duration. PMID- 27274498 TI - Intracranial meningiomas: Prognostic factors and treatment outcome in patients undergoing postoperative radiation therapy. AB - BACKGROUND: Meningioma constitutes 20% of the intracranial neoplasms. Followed by surgery as the primary treatment for most patients, radiotherapy becomes indicated in high-grade tumors with incomplete surgical removal. We evaluated the prognostic factors and overall outcome in meningioma patients who underwent radiotherapy. MATERIALS AND METHODS: In this retrospective analysis, data from all patients with documented diagnosis of meningioma who referred to the Omid and Ghaem Oncology Centers (Mashhad, Iran) from 2002 to 2013 were included. We calculated the overall survival rates using the Kaplan-Meier method and compared the survival curves between groups by the log-rank test. RESULTS: Eighty-three patients with a median age of 50 years (ranging: 16-84) were included. Grade I, II, and III meningiomas were seen in 40 (48%), 31 (37%), and 12 (15%) patients, respectively. Radiation therapy was indicated due to tumor recurrence, incomplete excision, or tumor grade in 32, 8, and 43 patients, respectively. Tumor grade had a significant effect on the overall survival with a 3-year overall survival of 76.7%, 43.5%, and 13.3% in Grade I, II, and III, respectively (P < 0.001). Gender, age, and tumor location were not correlated with the overall survival. Moreover, patients with Grade II and III who underwent total resection had a significantly higher overall survival than those with subtotal resection or biopsy alone (5-year survival rates of 82% vs. 17.1%, respectively; P = 0.008). CONCLUSION: Tumor grade was the most important prognostic factor in meningioma patients undergoing radiation therapy. In patients with Grade II and III tumors, the extent of surgical resection is significantly correlated with the overall survival. PMID- 27274499 TI - Autologous platelet-rich plasma compared with whole blood for the treatment of chronic plantar fasciitis; a comparative clinical trial. AB - BACKGROUND: Intralesional injection of autologous blood-derived products has recently gained attention as a potential treatment for plantar fasciitis (PF). We compared platelet-rich plasma (PRP) and whole blood (WB) for the treatment of chronic PF. MATERIALS AND METHODS: Patients with chronic PF received either an intralesional injection of 3 cc PRP prepared by double centrifuge technique or WB (n = 17 in each group). Overall, morning and walking pain severity were assessed by 11-point numerical rating scale, and function was assessed by the Roles and Maudsley score (RMS) at baseline and 1-month and 3 months after treatment. Ultrasonography was performed to measure plantar fascia thickness at baseline and 3 months after treatment. RESULTS: Pain scores were reduced over the study in the PRP (mean change = -5.00 +/- 1.17 to -5.47 +/- 1.46) and WB groups (mean change = -5.29 +/- 2.56 to -6.47 +/- 2.83), with no difference between groups (P > 0.05). One month and 3 months after treatment, successful treatment (RMS of <= 2) was respectively observed in 29.4% and 82.3% of the PRP and in 47.1% and 76.4% of the WB groups (P > 0.05). Also, fascia thickness was decreased in both the PRP and WB groups (mean change = -1.74 +/- 1.11 vs. -1.21 +/- 0.73 mm, respectively, P = 0.115). CONCLUSIONS: Significant improvement in pain and function, as well as decrease in plantar fascia thickness, was observed by intralesional injection of the PRP and WB in patients with chronic PF. The study results indicate similar effectiveness between PRP and WB for the treatment of chronic PF in short-term. PMID- 27274500 TI - Screening and evaluation of chronic and occult Hepatitis B in chemo - radiotherapy patients with cancer. AB - BACKGROUND: Hepatitis B virus infection (HBV) and its complications is one of the most serious problems of the health system in many parts of the world. In the present study, we will assess chronic and occult HBV and isolated anti-Hepatitis B core antigen whose screening and evaluation is not routine in different populations. MATERIALS AND METHODS: This descriptive analytical study was conducted on 213 patients undergoing chemotherapy - radiotherapy referred to the hematology - oncology clinics of Isfahan, Iran in 2012. In order to determine the serum levels of hepatitis B surface antigen (HbSAg), Hepatitis B Antigen and Antibody (HBCAb), aspartate aminotransferase (AST), alanine transaminase (ALT) and Alkaline phosphatase (ALK.P), venous blood samples were obtained. If the HBCAb sample was positive, another sample of the serum was sent to the laboratory to perform polymerase chain reaction and to determine viral load. RESULTS: The mean age of the patients was 47.7 +/- 9 years, with an age range of 27 -73 years; 98 (46%) and 115 (54%) cases were male and female, respectively, with mean age of 51.9 +/- 8.3 and 44.1 +/- 8.1 years, and there was no significant difference (P < 0.001). The mean level of liver enzymes including AST, ALT and ALK.P were 34.2 +/ 36.02, 38.9 +/- 47.1 and 252.1 +/- 234.7, respectively. Two cases were HbSAg positive (0.9%) and six cases were HBCAb positive (2.8%) and HbSAg negative. Three cases had a high viral load at the rate of starting treatment among positive anti-HBC patients. CONCLUSION: Because occult hepatitis is investigated less commonly in routine studies, it seems that screening and evaluating its prevalence is useful in the management of patients. PMID- 27274501 TI - Nasal colonization in children with community acquired methicillin-resistant Staphylococcus aureus. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of infections. The changing epidemiology of MRSA became evident in the 1990s when CA-MRSA cases were first reported. Nasal carriage of CA-MRSA is associated with an increased risk for development of infections in various populations. MATERIALS AND METHODS: Anterior nares culture for the presence of methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA was taken from 345 children attending kindergartens, who didn't have any known risk factor for MRSA colonization. Also, children demographic variables were recorded. Identification of SA and community-acquired methicillin-resistant Staphylococcus aureus (CA MRSA) with standard microbiological test was performed. Finally, the susceptibility of isolated to various antibiotics determined. The data were analyzed with Whonet 5.6 software. RESULTS: Of 345 children, 20 children (5.8%) were colonized with CA-MRSA, 86 children (24.9%) with MSSA and 239 cases (69.3%) didn't have SA colonization. The highest rate of MSSA and MRSA colonization was obtained at the age of 6 years. The frequency distribution of SA (MSSA and MRSA) colonization prevalence didn't have any significant differences based on age, gender and the admission time (P > 0.05); but it was significantly different in the urban areas (P < 0.001). The lowest resistance rate of CA-MRSA isolates, with a frequency of 10%, was detected with gentamicin, rifampin, and trimethoprim sulfamethoxazole. CONCLUSIONS: In summary, CA-MRSA colonization was observed in child care centers remarkably. Therefore, by facing various infections due to SA especially in areas of low socio-economic status, it must be considered. Based on antibiogram test, empirical treatment with rifampin, gentamicin and ciprofloxacin is recommended during CA-MRSA infections. PMID- 27274502 TI - Effect of drill-induced noise on hearing in non-operated ear. AB - BACKGROUND: The aim of this study was to evaluate the effect of drill-generated noise on hearing loss in non-operated ear and if any, was temporary or persistent. MATERIALS AND METHODS: In this prospective clinical study, 23 patients who had undergone mastoidectomy and normal contralateral hearing were enrolled. Patients were evaluated preoperatively and postoperatively (1 and 7 days) following surgery using low and high-frequency pure tone audiometry (PTA) and low and high-frequency transient evoked and distortion product otoacoustic emission (DPOAE) testing. RESULTS: Comparing preoperative and 1-day after surgery, PTA averages were significantly different at low frequencies, but no statistical significant differences were observed at 0.25 KHz and high frequencies. Comparing 1-day after surgery and 7 days after surgery showed that, PTA averages at 0.5, 2 and 2 KHz were significantly different with no significant differences at the other average of thresholds in low and high frequencies; PTA average at 1 KHz was significantly different with, no significant differences at the other averages of thresholds in low and high frequencies. DPOAEs showed a significant difference preoperative and 1-day after surgery, 1-day and 7 days after, but DPOAEs were not significantly different. Transiently evoked otoacoustic emissions (TEOAEs) had a significant difference preoperative and 1 day after surgery, 1-day and 7 days after but when comparing preoperative and 7 days after surgery, TEOAEs were not significantly different. CONCLUSIONS: Drill induced noise during ear surgery (mastoidectomy) can cause reversible changes in PTA, DPOAEs and TEOAEs in the non-operated ear. PMID- 27274503 TI - Effect of folic acid on homocysteine and insulin resistance of overweight and obese children and adolescents. AB - BACKGROUND: Considering the increasing trend of childhood obesity and subsequent burden of the disease in Iran and other countries and importance of early life intervention for achieving sustained effect on health of children and adolescents, this study aimed to investigate the effect of two different dose of folic acid on homocysteine (Hcy) level and insulin resistance of obese children. MATERIALS AND METHODS: In this randomized, double-blind controlled clinical trial study, 60 obese and overweight children aged 5-12 years were enrolled. Selected obese children randomly allocated in two interventional (1 mg/day folic acid and 5 mg/day folic acid, for 8 weeks) and one control groups. Biochemical measurements including folic acid, Hcy, insulin and insulin resistance were measured between and within groups before and after trial. RESULTS: In each group, 20 obese children were studied. The three groups were age and sex matched. After folic acid administration, mean of Hcy, insulin resistance and insulin decreased significantly in two groups which folic acid administrated with two different doses (P < 0.05). The reduction in studied biochemical variables was similar in two interventional groups (1 and 5 mg folic acid daily) (P > 0.05). Mean differences for Hcy, insulin resistance and insulin, in two intervention groups were significantly higher than the control group (P < 0.0001). Mean differences of Hcy, insulin resistance and insulin, in two intervention groups were not different significantly (P > 0.05). CONCLUSION: The findings of current trial showed that folic acid in two studied doses could be a safe and effective supplement for obese children to reduce Hcy level and insulin resistance, which consequently could prevent obesity-related complications including cardiovascular and metabolic disorders. PMID- 27274504 TI - An online questionnaire survey on preferred timing for the diagnosis and management of thyroid carcinoma in general population in Korea. AB - PURPOSE: An optimal timing for diagnosis and management of papillary thyroid microcarcinoma (PTMC) has become the subject for much controversy. The aim of the present study is to analyze people's preference in Korea for timing of diagnosis and management of PTMC using an online questionnaire. METHODS: The questionnaire consists of 3 questions about preference for the diagnosis and management of PTMC and 3 additional questions about respondents' personal information. An online survey was conducted from March 3 to June 3 in 2015 using Google Survey (http://goo.gl/forms/b81yEjqNUA). RESULTS: A total 2,308 persons (1,246 males, 1,053 females) answered the questionnaire. Respondents' ages varied widely from teenagers to 70-year-olds. If there was a suspicious thyroid nodule from PTMC measuring less than 1 cm in diameter, 95.7% of respondents want to know a cytological diagnosis for it. If a thyroid nodule turned out to be a PTMC, 59.5% of respondents wanted it removed immediately. For surgical management of PTMC, 53.0% of respondents were worried more about recurrences than complications. In subgroup analyses, respondents younger than 40 years old more often want immediate surgery than others: 66.7% vs. 32.7% (P < 0.05). Respondents who underwent thyroid cancer surgery (n = 91) were worried more about recurrences than others: 69.2% vs. 52.4% (P < 0.05). CONCLUSION: Almost all respondents in the present study wanted diagnosis of suspicious thyroid nodules immediately. However, there were opposing opinions about the preferred timing for surgical treatment and surgical extents. A patient's right to know their disease status and decision on treatments should be emphasized all the more. PMID- 27274505 TI - Risk factors for conversion to conventional laparoscopic cholecystectomy in single incision laparoscopic cholecystectomy. AB - PURPOSE: The aim of this study was to investigate the risk factors for conversion to conventional laparoscopic cholecystectomy (CLC) in single incision laparoscopic cholecystectomy (SILC) along with the proposal for procedure selection guidelines in treating patients with benign gallbladder (GB) diseases. METHODS: SILC was performed in 697 cases between April 2010 and July 2014. Seventeen cases (2.4%) underwent conversion to conventional LC. We compared these 2 groups and analyzed the risk factors for conversion to CLC. RESULTS: In univariate analysis, American Society of Anesthesiologist score > 3, preoperative percutaneous transhepatic GB drainage status and pathology (acute cholecystitis or GB empyema) were significant risk factors for conversion (P = 0.010, P = 0.019 and P < 0.001). In multivariate analysis, pathology (acute cholecystitis or GB empyema) was significant risk factors for conversion to CLC in SILC (P < 0.001). CONCLUSION: Although SILC is a feasible method for most patients with benign GB disease, CLC has to be considered in patients with acute cholecystitis or GB empyema because it is likely to result in inadequate visualization of the Calot's triangle and greater bleeding risk. PMID- 27274506 TI - Who experiences endoscopic retrograde cholangiopancreatography after laparoscopic cholecystectomy for symptomatic gallstone disease? AB - PURPOSE: Laparoscopic cholecystectomy (LC) has become a standard treatment of symptomatic gallstone disease. But, some patients suffer from retained common bile duct stones after LC. The aim of this study is to analyze the predicting factors associated with subsequent postoperative endoscopic retrograde cholangiopancreatography (ERCP) after LC. METHODS: We retrospectively reviewed a database of every LC performed between July 2006 and September 2012. We classify 28 patients who underwent ERCP within 6 months after LC for symptomatic gallstone disease as the ERCP group and 56 patients who underwent LC for symptomatic gallstone disease during same period paired by sex, age, underlying disease, operation history, and body mass index as the control group. To identify risk factor performing postoperative ERCP after LC, we compared admission route, preoperative biochemical liver function test, number of gall stones, gallstone size, adhesion around GB, wall thickening of GB, and existence of acute cholecystitis between the 2 groups. RESULTS: Admission route, preoperative AST, ALT, and ALP, stone size, longer operation time, and acute cholecystitis were identified as risk factors of postoperative ERCP in univariate analyses. But, longer operation time (P = 0.004) and acute cholecystitis (P = 0.048) were identified as independent risk factors of postoperative ERCP in multivariate analyses. CONCLUSION: The patient who underwent ERCP after LC for symptomatic gallstone disease are more likely experienced longer operation time and acute cholecystitis than the patient who did not undergo ERCP after LC. PMID- 27274507 TI - The effects of scalpel, harmonic scalpel and monopolar electrocautery on the healing of colonic anastomosis after colonic resection. AB - PURPOSE: In our study, the effects of harmonic scalpel, scalpel, and monopolar electrocautery usage on the health and healing of colon anastomosis after resection was investigated. METHODS: In this study, 120 female albino Wistar rats were divided into 3 groups each containing 40 rats. Group A, resection with scalpel; group B, resection with monopolar electrocautery; group C, resection with harmonic scalpel. The groups were divided into 4 subgroups consisting of 10 rats and analysed in the postoperative 1st, 3rd, 5th, and 7th days. Anastomotic bursting pressures, hydroxyproline levels and histopathological parameters were surrogate parameters for evaluating wound healing. RESULTS: The tissue hydroxyproline levels did not show any significant difference between the groups and subgroups. The mean bursting pressure of group A on the 5th day was significantly higher than groups B and C (P < 0.001). When the fibroblast and fibrosis scores were evaluated, scores of group C on the 5th day were significantly higher than the other groups, but the results of bursting pressures and biochemical parameters did not support the fibroblast and fibrosis scores. There were not any significant differences between the groups in other histopathologic parameters. CONCLUSION: The use of monopolar electrocautery needs more attention since the device causes tissue destruction. The obliterating effect of harmonic scalpel on luminal organs is an important problem, especially if an anastomosis is planned. Despite the disadvantages of scalpel, its efficacy on early wound healing is better than the other devices. PMID- 27274508 TI - Preoperative thrombocytosis predicts prognosis in stage II colorectal cancer patients. AB - PURPOSE: Thrombocytosis is known to be a poor prognostic factor in several types of solid tumors. The prognostic role of preoperative thrombocytosis in colorectal cancer remains limited. The aim of this study is to investigate the prognostic role of preoperative thrombocytosis in stage II colorectal cancer. METHODS: Two hundred eighty-four patients with stage II colorectal cancer who underwent surgical resection between December 2003 and December 2009 were retrospectively reviewed. Thrombocytosis was defined as platelet > 450 * 10(9)/L. We compared patients with thrombocytosis and those without thrombocytosis in terms of survival. RESULTS: The 5-year disease-free survival (DFS) rates were lower in patients with thrombocytosis compared to those without thrombocytosis in stage II colorectal cancer (73.3% vs. 89.6%, P = 0.021). Cox multivariate analysis demonstrated that thrombocytosis (hazard ratio, 2.945; 95% confidence interval, 1.127-7.697; P = 0.028) was independently associated with DFS in patients with stage II colorectal cancer. CONCLUSION: This study showed that thrombocytosis is a prognostic factor predicting DFS in stage II colorectal cancer patients. PMID- 27274509 TI - Comparison of perioperative and short-term outcomes between robotic and conventional laparoscopic surgery for colonic cancer: a systematic review and meta-analysis. AB - PURPOSE: Reports from several case series have described the feasibility and safety of robotic surgery (RS) for colonic cancer. Experience is still limited in robotic colonic surgery, and a few meta-analysis has been conducted to integrate the results for colon cancer specifically. We conducted a systematic review of the available evidence comparing the surgical safety and efficacy of RS with that of conventional laparoscopic surgery (CLS) for colonic cancer. METHODS: We searched English databases (MEDLINE, Embase, and Cochrane Library), and Korean databases (KoreaMed, KMbase, KISS, RISS, and KisTi). Dichotomous variables were pooled using the risk ratio, and continuous variables were pooled using the mean difference (MD). RESULTS: The present study found that the RS group had a shorter time to resumption of a regular diet (MD, -0.62 days; 95% CI, -0.97 to -0.28), first passage of flatus (MD, -0.44 days; 95% CI, -0.66 to -0.23) and defecation (MD, -0.62 days; 95% CI, -0.77 to -0.47). Also, RS was associated with a shorter hospital stay (MD, -0.69 days; 95% CI, -1.12 to -0.26), a lower estimated blood loss (MD, -19.49 mL; 95% CI, -27.10 to -11.89) and a longer proximal margin (MD, 2.29 cm; 95% CI, 1.11-3.47). However, RS was associated with a longer surgery time (MD, 51.00 minutes; 95% CI, 39.38-62.62). CONCLUSION: We found that the potential benefits of perioperative and short-term outcomes for RS than for CLS. For a more accurate understanding of RS for colonic cancer patients, robust comparative studies and randomized clinical trials are required. PMID- 27274510 TI - Thrombophilia in Korean patients with arterial or venous thromboembolisms. AB - PURPOSE: To determine the prevalence of thrombophilia in Korean patients with an arterial thromboembolism (ATE) or a venous thromboembolism (VTE), and to evaluate the characteristic of VTE in patients with thrombophilia. METHODS: Hospital records of 294 patients (228 with VTE, 66 with ATE) including two foreign ones (mean age, 51.4 years) who underwent thrombophilia testing between August 2006 and March 2015 were reviewed retrospectively. In general, such screening was performed according to the guidelines of the international consensus statement for VTE. Thrombophilia testing included evaluations of the factor V Leiden and prothrombin G20210A mutations, levels of proteins C and S and antithrombin, and antiphospholipid antibody syndrome (APLS). RESULTS: A factor V Leiden mutation was not found in the 292 Korean patients. A prothrombin G21210A mutation was investigated in 33 patients but none was found. Among 226 Korean patients with VTE, 130 demonstrated no thrombophilia and 55 patients did after exclusion of 41 patients without confirmatory test. The most common form was protein S deficiency (31 of 55, 56%) followed by protein C deficiency, antithrombin deficiency, and APLS. When comparing patients with a VTE or deep vein thrombosis (DVT) according to the presence of thrombophilia, thrombophilia was associated with younger age (P = 0.001 for VTE; P < 0.001 for DVT) and a family history (P < 0.001 for VTE and DVT). CONCLUSION: We did not find any factor V Leiden mutation in Korean subjects at high risk for thrombophilia. Therefore, this testing is not warranted. Thrombophilia was associated with VTE in younger age and a family history. PMID- 27274511 TI - Uncomplicated jejunal diverticulosis with pneumoperitoneum. AB - Small bowel diverticulosis is a rare finding within all bowel diverticuloses and jejunal diverticulosis is even rarer. Their relative clinical rarity and varied presentation may make diagnosis both delayed and difficult. We experienced a case of jejunal diverticulosis, which was diagnosed intraoperatively. A 55-year-old woman was admitted to Emergency Department with pneumoperitoneum on plain chest and abdominal film from a local clinic. She was hemodynamically stable with minimal tenderness on the left upper quadrant of the abdomen but no rebound tenderness. At surgery, small bowel torsion and jejunal diverticulosis were confirmed. Over 30 variable sized small bowel diverticula were noted on the mesenteric side of the proximal jejunum. The affected segment of the jejunum was about 180 cm. On exploration, we could not find any perforation site. No postoperative complications were observed, and the patient made a full recovery. Jejunal diverticulosis is rare, but it should not be regarded as insignificant. PMID- 27274512 TI - Isolated cystic duct cyst with associated stones in a 4-month-old boy. AB - Isolated cystic duct cysts are rare entities, with few cases having been reported. We present the case of a 4-month-old male patient presenting with abdominal pain and vomiting. Ultrasonography and magnetic resonance cholangiopancreatography revealed an isolated cystic duct cyst with associated stones. The patient underwent open cholecystectomy with complete cyst excision and cystic duct transection; there were no postoperative complications. While lesions like the one described herein are extremely rare, they should be included as a separate category in classifications of choledochal cysts. PMID- 27274513 TI - Central Venous Pressure Monitoring; Introduction of a New Device. PMID- 27274514 TI - Comparison of Ultrasonography and Radiography in Detection of Thoracic Bone Fractures; a Systematic Review and Meta-Analysis. AB - INTRODUCTION: The potential benefit of ultrasonography for detection of thoracic bone fractures has been proven in various surveys but no comprehensive conclusion has been drawn yet; therefore, the present study aimed to conduct a thorough meta analytic systematic review on this subject. METHODS: Two reviewers independently carried out a comprehensive systematic search in Medline, EMBASE, ISI Web of Knowledge, Scopus, Cochrane Library, and ProQuest databases. Data were summarized as true positive, false positive, true negative and false negative and were analyzed via STATA 11.0 software using a mixed-effects binary regression model. Sources of heterogeneity were further assessed through subgroup analysis. RESULTS: Data on 1667 patients (807 subjects with and 860 cases without thoracic fractures), whose age ranged from 0 to 92 years, were extracted from 17 surveys. Pooled sensitivity and specificity of ultrasonography in detection of thoracic bone fractures were 0.97 (95% CI: 0.90-0.99; I2= 88.88, p<0.001) and 0.94 (95% CI: 0.86-0.97; I2= 71.97, p<0.001), respectively. The same measures for chest radiography were found to be 0.77 (95% CI: 0.56-0.90; I2= 97.76, p<0.001) and 1.0 (95% CI: 0.91-1.00; I2= 97.24, p<0.001), respectively. The sensitivity of ultrasonography was higher in detection of rib fractures, compared to fractures of sternum or clavicle (97% vs. 91%). Moreover, the sensitivity was found to be higher when the procedure was carried out by a radiologist in comparison to an emergency medicine specialist (96% vs. 90%). CONCLUSION: Base on the findings of the present meta-analysis, screening performance characteristic of ultrasonography in detection of thoracic bone fractures was found to be higher than radiography. However, these characteristics were more prominent in detection of rib fractures and in cases where was performed by a radiologist. PMID- 27274515 TI - Ventilator Weaning and Spontaneous Breathing Trials; an Educational Review. AB - The term "weaning" is used to describe the gradual process of decreasing ventilator support. It is estimated that 40% of the duration of mechanical ventilation is dedicated to the process of weaning. Spontaneous breathing trial (SBT) assesses the patient's ability to breathe while receiving minimal or no ventilator support. The collective task force in 2001 stated that the process of SBT and weaning should start by assessing whether the underlying cause of respiratory failure has been resolved or not. Weaning predictors are parameters that are intended to help clinicians predict whether weaning attempts will be successful or not. Although the international consensus conference in 2005 did not recommend their routine use for clinical decision making, researchers did not stop working in this area. In the present article, we review some of the recent studies about weaning predictors, criteria, procedure, as well as assessment for extubation a mechanically ventilated patient. PMID- 27274517 TI - Effective Factors in Severity of Traffic Accident-Related Traumas; an Epidemiologic Study Based on the Haddon Matrix. AB - INTRODUCTION: Traffic accidents are the 8(th) cause of mortality in different countries and are expected to rise to the 3(rd) rank by 2020. Based on the Haddon matrix numerous factors such as environment, host, and agent can affect the severity of traffic-related traumas. Therefore, the present study aimed to evaluate the effective factors in severity of these traumas based on Haddon matrix. METHODS: In the present 1-month cross-sectional study, all the patients injured in traffic accidents, who were referred to the ED of Imam Khomeini and Golestan Hospitals, Ahvaz, Iran, during March 2013 were evaluated. Based on the Haddon matrix, effective factors in accident occurrence were defined in 3 groups of host, agent, and environment. Demographic data of the patients and data regarding Haddon risk factors were extracted and analyzed using SPSS version 20. RESULTS: 700 injured people with the mean age of 29.66 +/- 12.64 years (3-82) were evaluated (92.4% male). Trauma mechanism was car-pedestrian in 308 (44%) of the cases and car-motorcycle in 175 (25%). 610 (87.1%) cases were traffic accidents and 371 (53%) occurred in the time between 2 pm and 8 pm. Violation of speed limit was the most common violation with 570 (81.4%) cases, followed by violation of right-of-way in 57 (8.1%) patients. 59.9% of the severe and critical injuries had occurred on road accidents, while 61.3% of the injuries caused by traffic accidents were mild to moderate (p < 0.001). The most common mechanisms of trauma for critical injuries were rollover (72.5%), motorcycle-pedestrian (23.8%), and car-motorcycle (13.14%) accidents (p < 0.001). CONCLUSION: Based on the results of the present study, the most important effective factors in severity of traffic accident-related traumas were age over 50, not using safety tools, and undertaking among host-related factors; insufficient environment safety, road accidents and time between 2 pm and 8 pm among environmental factors; and finally, rollover, car-pedestrian, and motorcycle-pedestrian accidents among the agent factors. PMID- 27274516 TI - Unintentional Home Injury Prevention in Preschool Children; a Study of Contributing Factors. AB - INTRODUCTION: Different factors such as parents' knowledge and attitudes regarding preventive measures (PM) have a great role in reducing children unintentional home injuries. The present study aims to evaluate the contributing factors of unintentional home injury prevention in preschool victims presented to the emergency department. METHODS: The subjects consisted of all the mothers of preschool children who were presented to the emergency department of Imam Hossein and Shohadaie-Hafte-Tir Hospitals, with unintentional home injuries, from March 2011 to February 2012. The participants were divided into two groups according to implementation of preventive measures status. The significant confounding factors of PM application was determined by chi-squared test and entered into the backward multivariate logistic regression model. RESULTS: 230 mothers with the mean age of 29.4 +/- 5.2 years were evaluated. 225 (97.83%) of them were still married, 74 (32.17%) had high school education or higher, 122 (53.04%) were homemakers, and 31 (13.49%) worked outside the home for at least 8 hours daily. High level of knowledge (OR = 0.05; 95% CI: 0.002-0.32; P = 0.002), appropriate attitude (OR = 0.12; 95% CI: 0.03-0.51; P = 0.01), having at least three children (OR = 7.2; 95% CI: 1.1-32.9; P = 0.04), daily absence of mother for at least 8 hours (OR = 9.2; 95% CI: 2.2-35.46; P = 0.002), and a history of home injury during the previous 3 weeks (OR = 8.3; 95% CI: 2.1-41.3; P = 0.001) were independent factors which influenced application of preventive measures. CONCLUSION: Increasing mothers' knowledge level and improving their attitudes were facilitating factors and mothers' absence from the house for more than 8 hours a day and having at least 3 children were obstacles to application of preventive measures. In addition, a history of same injury during the previous 3 weeks increased the risk of repeated event. PMID- 27274518 TI - Correlation between Central Venous Pressure and Inferior Vena Cava Sonographic Diameter; Determining the Best Anatomic Location. AB - INTRODUCTION: The correlation of central venous pressure (CVP) with inferior vena cava (IVC) sonographic diameter has been reported in several studies. However, few studies have attempted to find the best anatomic location of measurement. Therefore, the purpose of this study was determining the best anatomic location to find precise correlation between CVP and IVC diameter using transesophageal echocardiography (TEE). METHODS: In the present diagnostic accuracy study, patients in need of central venous catheterization and TEE were enrolled. Maximum diameter of IVC were measured during expiratory phase of respiratory cycle at the level of diaphragm, 2cm above the diaphragm and at the point of entry into the right atrium using SonoSite TEE device. CVP was measured using an electronic transducer connected to the central venous line. The best location for sonography was determined via calculating and comparing area under the receiver operating characteristics (ROC) curve (AUC). RESULTS: 39 patients were enrolled (53.8% female). Mean CVP was 6.8 +/- 1.4 mmHg and 25 (64.1%) patients had normal CVP, while 14 (35.9%) showed elevated CVP (> 6 mmHg). Evaluating AUC showed that IVC diameter (p = 0.01), aorta diameter (p = 0.01) and IVC / aorta ratio (p = 0.004) had acceptable correlation with CVP. Point of entry of IVC into the right atrium with AUC of 0.98 (95% CI: 0.95 - 1.00) was the location of highest correlation with CVP. CONCLUSION: Based on the present findings, the IVC sonographic diameter and IVC / aorta ratio had acceptable correlation with CVP at the level of IVC entry into the right atrium. PMID- 27274519 TI - Acute Physiology and Chronic Health Evaluation (APACHE) III Score compared to Trauma-Injury Severity Score (TRISS) in Predicting Mortality of Trauma Patients. AB - INTRODUCTION: More than 50 scoring systems have been published for classification of trauma patients in the field, emergency room, and intensive care settings, so far. The present study aimed to compare the ability of trauma injury severity score (TRISS) and acute physiology and chronic health evaluation (APACHE) III in predicting mortality of intensive care unit (ICU) admitted trauma patients. METHODS: This prospective cross-sectional study included ICU admitted multiple trauma patients of Imam Hossein and Hafte-Tir Hospitals, Tehran, Iran, during 2011 and 2012. Demographic data, vital signs, mechanism of injury and required variables for calculating APACHE III score and TRISS were recorded. The accuracy of the two models in predicting mortality of trauma patients was compared using area under the ROC curve. RESULTS: 152 multiple trauma patients with mean age of 37.09 +/- 14.60 years were studied (78.94% male). 48 (31.57%) cases died. For both APACHE III and TRISS, predicted death rates significantly correlated with observed death rates (p < 0.0001). The mean age of dead patients was 37.21 +/- 14.07 years compared to 37.03+/-14.96 years for those who survived (p = 0.4). The area under ROC curve was 0.806 (95% CI: 0.663-0.908) for TRISS and 0.797 (95% CI: 0.652-0.901) for APACHE III (p = 0.2). CONCLUSION: Based on the results of this study, both TRISS and APACHE models have the same accuracy in predicting mortality of ICU admitted trauma patients. Therefore, it seems that TRISS model would be more applicable in this regard because of its easier calculation, consideration of trauma characteristics, and independency of patient care quality. PMID- 27274520 TI - Remifentanil versus Fentanyl/Midazolam in Painless Reduction of Anterior Shoulder Dislocation; a Randomized Clinical Trial. AB - INTRODUCTION: Performance of painful diagnostic and therapeutic procedures is common in emergency department (ED), and procedural sedation and analgesia (PSA) is a fundamental skill for every emergency physician. This study was aim to compare the efficacy of remifentanil with fentanyl/midazolam in painless reduction of anterior shoulder dislocation. METHOD: In this randomized, double blind, clinical trial the procedural characteristics, patients' satisfaction as well as adverse events were compared between fentanyl/midazolam and remifentanil for PSA of 18-64 years old patients, which were presented to ED following anterior shoulder dislocation. RESULTS: 96 cases were randomly allocated to two groups (86.5% male). There were no significant difference between groups regarding baseline characteristics. Remifentanil group had lower duration of procedure (2.5 +/- 1.6 versus 4.6 +/- 1.8 minutes, p < 0.001), higher pain reduction (53.7 +/- 13.3 versus 33.5 +/- 19.6, p < 0.001), lower failure rate (1 (2.1%) versus 15 (31.3%), p < 0.001), higher satisfaction (p = 0.005). Adverse events were seen in 12 (25%) patients in midazolam/fentanyl and 8 (16.7%) cases in remifentanil group (p = 0.122). CONCLUSION: It seems that use of remifentanil resulted in lower procedural time, lower failure rate, and lower pain during procedure as well as higher patient satisfaction in comparison with midazolam/fentanyl combination in anterior shoulder dislocation. PMID- 27274522 TI - Ultrasound and Perforated Viscus; Dirty Fluid, Dirty Shadows, and Peritoneal Enhancement. AB - Early detection of free air in the peritoneal cavity is vital in diagnosis of life-threatening emergencies, and can play a significant role in expediting treatment. We present a series of cases in which bedside ultrasound (US) in the emergency department accurately identified evidence of free intra-peritoneal air and echogenic (dirty) free fluid consistent with a surgical final diagnosis of a perforated hollow viscus. In all patients with suspected perforated viscus, clinicians were able to accurately identify the signs of pneumoperitoneum including enhanced peritoneal stripe sign (EPSS), peritoneal stripe reverberations, and focal air collections associated with dirty shadowing or distal multiple reflections as ring down artifacts. In all cases, hollow viscus perforation was confirmed surgically. It seems that, performing US in patients with suspected perforated viscus can accurately identify presence of intra peritoneal echogenic or "dirty" free fluid as well as evidence of free air, and may expedite patient management. PMID- 27274521 TI - Sudden Death Following Exercise; a Case Series. AB - INTRODUCTION: Natural and unexpected death that happens within less than one hour of first symptom occurrence is called sudden death. Cardiovascular diseases are the main known reason of sudden death and more than 75% of sudden deaths in athletes are assigned to it. Here we reported the autopsy results of all cases with sudden death following exercise that were referred to forensic center of Tehran, Iran, from 2009 to 2014. METHODS: In this cross sectional study all subjects who were registered to forensic medicine center of Tehran, Iran, from 2009 to 2014, as a case of sudden death following exercise were evaluated. Demographic data and medical history as well as autopsy and toxicology findings were retrospectively gathered using profiles of the deceased. Results were reported using descriptive analysis. RESULTS: 14 cases were registered as sudden death following exercise in forensic medicine profiles during the study period. Exploring the files of the mentioned deceased, revealed five non-compatible cases in this regard. Finally, 9 eligible cases were enrolled (88.9% male). The mean age of the deceased was 28.66 +/- 10.86 years (range: 7 - 40). Toxicological tests were available for 7 cases, one of which was positive for tramadol. Sudden death following football was reported most frequently (44.4%). Only 3 (33.3%) cases had herald signs such as chest pain, syncope, or loss of consciousness. 1 case (11.11%) had a positive history of sudden death in relatives. CONCLUSION: Although most sudden death victims are asymptomatic until the event, all those who suffer from symptoms such as chest pain, shortness of breath, dizziness, fatigue and irregular heart rate during physical activities, should be screened regarding common probable causes of sudden death. PMID- 27274523 TI - Peganum Harmala (Aspand) Intoxication; a Case Report. AB - There are several reports in the literature indicating a great variety of pharmacological effects for peganum harmala or aspand such as sedative anti bacterial, anti-fungal, antiviral and antiprotozoal. Some people believe that can be used for treatment of some organic or psychiatric disorders. We introduce a woman with history of long time constipation that was disappointed in novel medical treatment and decided to use comminuted Aspand to relieve her problem. Two hours after use, the intoxication symptoms manifested as blurred vision, phonophobia, floating feeling, and tinnitus ringing. Here we report the treatment process and outcome of this case. PMID- 27274524 TI - Eosinophilic Gastroenteritis as a Rare Cause of Recurrent Epigastric Pain. AB - Eosinophilic gastroenteritis (EGE) is a rare inflammatory disorder of gastrointestinal tract characterized by eosinophilic infiltration of the bowel wall. It can mimic many gastrointestinal disorders due to its wide spectrum of presentations. Diagnose is mostly based on excluding other disorders and a high suspicion. Here we report a case of 26 year old man with a history of sever epigastric pain followed by nausea, vomiting since a few days before admission with final diagnosis of EGE. PMID- 27274525 TI - Evidence Based Emergency Medicine; Part 5 Receiver Operating Curve and Area under the Curve. PMID- 27274526 TI - Data on heavy metals and selected anions in the Persian popular herbal distillates. AB - In this data article, we determined the concentration levels of heavy metals including Pb, Co, Cd, Mn, Mg, Fe and Cu as well as selected anions including [Formula: see text] , [Formula: see text], [Formula: see text] and [Formula: see text] in the most used and popular herbal distillates in Iran. It is well known that heavy metals may pose a serious health hazard due to their bioaccumulation throughout the trophic chain ("Heavy metals (Cd, Cu, Ni and Pb) content in two fish species of Persian Gulf in Bushehr Port, Iran" (Dobaradaran et al., 2013) [1]; "Comparative investigation of heavy metal, trace, and macro element contents in commercially valuable fish species harvested off from the Persian Gulf" (Abadi et al., 2015) [2]) as well as some other environmental pollutions, "Assessment of sediment quality based on acid-volatile sulfide and simultaneously extracted metals in heavily industrialized area of Asaluyeh, Persian Gulf: concentrations, spatial distributions, and sediment bioavailability/toxicity" (Arfaeinia et al., 2016) [3]. The concentration levels of heavy metals and anions in herbal distillates samples were determined using flame atomic absorption spectrometry (FAAS, Varian AA240, Australia) and a spectrophotometer (M501 Single Beam Scanning UV/VIS, UK) respectively. PMID- 27274527 TI - Data on the peptide mapping and MS identification for phosphorylated peptide. AB - This article contains peptides mapping, mass spectrometry and processed data related to the research "Identification and quantification of the phosphorylated ovalbumin by high resolution mass spectrometry under dry-heating treatment" [1]. Fourier transform ion cyclotron mass spectrometry (FTICR MS) was used to investigate the specific phosphorylation sites and the degree of phosphorylation (DSP) at each site. Specifically, phosphorylated peptides were monitored through mass shift on the FTICR MS spectrum. DSP was evaluated through the relative abundance levels of the FTICR MS spectrometry. From these data, the calculation method of DSP was exemplified. PMID- 27274528 TI - Data from mass spectrometry, NMR spectra, GC-MS of fatty acid esters produced by Lasiodiplodia theobromae. AB - The data described herein is related to the article with the title "Fatty acid esters produced by Lasiodiplodia theobromae function as growth regulators in tobacco seedlings" C.C. Uranga, J. Beld, A. Mrse, I. Cordova-Guerrero, M.D. Burkart, R. Hernandez-Martinez (2016) [1]. Data includes nuclear magnetic resonance spectroscopy and GC-MS data used for the identification and characterization of fatty acid esters produced by L. theobromae. GC-MS traces are also shown for incubations in defined substrate, consisting in Vogel's salts supplemented with either 5% grapeseed oil or 5% glucose, the two combined, or 5% fructose. Traces for incubations in the combination of 5% grapeseed oil and 5% glucose for different fungal species are also included. Images of mycelium morphology when grown in 5% glucose with or without 5% grapeseed oil are shown due to the stark difference in mycelial pigmentation in the presence of triglycerides. High concentration gradient data for the plant model Nicotiana tabacum germinated in ethyl stearate (SAEE) and ethyl linoleate (LAEE) is included to show the transition between growth inhibition and growth induction in N. tabacum by these compounds. PMID- 27274529 TI - Data on dynamic study of cytoophidia in Saccharomyces cerevisiae. AB - The data in this paper are related to the research article entitled "Filamentation of metabolic enzymes in Saccharomyces cerevisiae" Q.J. Shen et al. (2016) [1]. Cytoophidia are filamentous structures discovered in fruit flies (doi:10.1016/S1673-8527(09)60046-1) J.L. Liu (2010) [2], bacteria (doi:10.1038/ncb2087) M. Ingerson-Mahar et al. (2010) [3], yeast (doi:10.1083/jcb.201003001; doi:10.1242/bio.20149613) C. Noree et al. (2010) and J. Zhang, L. Hulme, J.L. Liu (2014) [4], [5] and human cells (doi:10.1371/journal.pone.0029690; doi:10.1016/j.jgg.2011.08.004) K. Chen et al. (2011) and W.C. Carcamo et al. (2011) ( [6], [7]. However, there is little research on the motility of the cytoophidia. Here we selected cytoophidia formed by 6 filament-forming proteins in the budding yeast S. cerevisiae, and performed living-cell imaging of cells expressing the proteins fused with GFP. The dynamic features of the six types of cytoophidia were analyzed. In the data, both raw movies and analysed results of the dynamics of cytoophidia are presented. PMID- 27274530 TI - Data on the gene expression of cardiomyocyte exposed to hypothermia. AB - Hypothermia is widely used in neurosurgery and cardiac surgeries. However, little is known about the underlying molecular mechanisms. We previously reported that the transcriptome responses of cardiomyocyte exposed to hypothermia, "The transcriptome responses of cardiomyocyte exposed to hypothermia" [4]. Herein, we provide the hypothermia inhibited proliferation of cardiomyocyte cells in vitro and the details of transcription factors in regulation of differentially expressed genes. PMID- 27274531 TI - Data on morphological features of mycosis induced by Colletotrichum nymphaeae and Lecanicillium longisporum on citrus orthezia scale. AB - We describe symptoms of mycosis induced by two native fungal entomopathogens of the citrus orthezia scale, Praelongorthezia praelonga (Hemiptera: Ortheziidae), an important pest of citrus orchards. The data presented in this article are related to the article entitled "Seasonal prevalence of the insect pathogenic fungus Colletotrichum nymphaeae in Brazilian citrus groves under different chemical pesticide regimes" [1]. The endemic fungal pathogen, C. nymphaeae, emerges through the thin cuticular intersegmental regions of the citrus orthezia scale body revealing orange salmon-pigmented conidiophores bearing conidial masses, as well as producing rhizoid-like hyphae that extend over the citrus leaf. By contrast, nymphs or adult females of this scale insect infected with Lecanicillium longisporum exhibit profuse outgrowth of bright white-pigmented conidiophores with clusters of conidia emerging from the insect intersegmental membranes, and mycosed cadavers are commonly observed attached to the leaf surface by hyphal extensions. These morphological differences are important features to discriminate these fungal entomopathogens in citrus orthezia scales. PMID- 27274532 TI - Proteomics data in support of the quantification of the changes of bovine milk proteins during mammary gland involution. AB - Here we provide data from three proteomics techniques; two-dimensional electrophoresis (2-DE) followed by identification of selected spots using PSD MALDI-TOF MS/MS, one-dimensional gel electrophoresis followed by LC-MS/MS analysis of gel slices (GeLC) and dimethyl isotopic labelling of tryptic peptides followed by Orbitrap MS/MS (DML), to quantify the changes in the repertoire of bovine milk proteins that occurs after drying off. We analysed skim milk and whey sampled at day 0 and either day 3 or day 8 after drying off. These analyses identified 45 spots by MALDI-TOF, 51 proteins by GeLC and 161 proteins by DML, for which the detailed data work-up is presented as three Excel files. The data supplied in this article supports the accompanying publication "Changes in the repertoire of bovine milk proteins during mammary involution" (Boggs et al., 2015) [1]. Data are available via ProteomeXchange with identifiers ProteomeXchange: PXD003110 and ProteomeXchange: PXD003011. PMID- 27274533 TI - Data on the identification of protein interactors with the Evening Complex and PCH1 in Arabidopsis using tandem affinity purification and mass spectrometry (TAP MS). AB - Tandem affinity purification coupled with mass spectrometry (TAP-MS) analysis is a powerful biochemical approach to identify protein-protein associations. Here we describe two datasets generated by a series of TAP-MS analyses to co-purify proteins associated with either ELF3 or ELF4 of the Evening Complex (EC) ("Identification of Evening Complex Associated Proteins in Arabidopsis by Affinity Purification and Mass Spectrometry" (Huang et al., 2016a) [1]) or proteins associated with PCH1, which is a newly identified output of the circadian clock to regulate photoperiodic growth in Arabidopsis thaliana ("PCH1 integrates circadian and light-signaling pathways to control photoperiod responsive growth in Arabidopsis" (Huang et al. 2016b) [2]). We used either ELF3, ELF4 or PCH1 fused to a C-terminal tandem affinity tag (6xHis-3xFLAG) as baits and conducted purifications in various genetic mutant backgrounds. These data are discussed in recent publications [1,2], and are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PRIDE: PXD002606 (for EC) and PRIDE: PXD003352 (for PCH1). PMID- 27274534 TI - Whole transcriptome data analysis of zebrafish mutants affecting muscle development. AB - Formation of the contractile myofibril of the skeletal muscle is a complex process which when perturbed leads to muscular dystrophy. Herein, we provide a mRNAseq dataset on three different zebrafish mutants affecting muscle organization during embryogenesis. These comprise the myosin folding chaperone unc45b (unc45b-/-), heat shock protein 90aa1.1 (hsp90aa1.1-/-) and the acetylcholine esterase (ache-/-) gene. The transcriptome analysis was performed in duplicate experiments at 72 h post-fertilization (hpf) for all three mutants, with two additional times of development (24 hpf and 48 hpf) for unc45b-/-. A total of 20 samples were analyzed by hierarchical clustering for differential gene expression. The data from this study support the observation made in Etard et al. (2015) [1] (http://dx.doi.org/10.1186/s13059-015-0825-8) that a failure to fold myosin activates a unique transcriptional program in the skeletal muscles that is different from that induced in stressed muscle cells. PMID- 27274535 TI - Koenen's tumor and facial angiofibromas in a case of Birt-Hogg-Dube syndrome: A cutaneous contribution to growing evidence of a relationship with tuberous sclerosis complex. PMID- 27274536 TI - Surgical removal of a noninvoluting congenital hemangioma using a modified sub brow flap. PMID- 27274537 TI - Urogynecologic complications in Stevens-Johnson syndrome and toxic epidermal necrolysis: Presentation of a case and recommendations for management. PMID- 27274538 TI - Keratoacanthoma centrifugum marginatum: A diagnostic and therapeutic challenge. PMID- 27274539 TI - Peroral endoscopic myotomy for Jackhammer esophagus: to cut or not to cut the lower esophageal sphincter. AB - BACKGROUND AND STUDY AIMS: With the success of peroral endoscopic myotomy (POEM) in treatment of achalasia, its successful application to other spastic esophageal motility disorders such as Jackhammer esophagus has been noted. The question of whether the lower esophageal sphincter (LES) should be included in the myotomy for Jackhammer esophagus is a topic of current debate. Here, we report our experience and results with four patients with Jackhammer esophagus treated with POEM. The clinical and manometric results are presented and their potential implications are discussed. PATIENTS AND METHODS: Between January 2014 and July 2015, four patients underwent POEM for treatment of Jackhammer esophagus at our center. Manometry was performed prior to and after POEM. All patients met the Chicago classification criteria for Jackhammer esophagus and received a barium esophagram and endoscopic examination before having POEM. RESULTS: All patients had uneventful procedures without any intraoperative or post-procedure complications. Patients in which the LES was included during POEM had resolution or significant improvement in symptoms. One patient in whom the LES was preserved had resolution of chest pain but developed significant dysphagia and regurgitation. Subsequently this individual received a repeat POEM which included the LES, resulting in symptom resolution. CONCLUSIONS: POEM is a suitable treatment for patients with Jackhammer esophagus. Until there are larger-scale randomized studies, we speculate that based on our clinical experience and physiologic and manometric observations, obligatory inclusion of the LES is justified to reduce the risk of symptom development from iatrogenic ineffective esophageal motility or subsequent progression to achalasia. PMID- 27274542 TI - Why should I join my specialty societies? PMID- 27274540 TI - Screening for novel hexanucleotide repeat expansions at ALS- and FTD-associated loci. AB - OBJECTIVE: To determine whether GGGGCC (G4C2) repeat expansions at loci other than C9orf72 serve as common causes of amyotrophic lateral sclerosis (ALS). METHODS: We assessed G4C2 repeat number in 28 genes near known ALS and frontotemporal dementia (FTD) loci by repeat-primed PCR coupled with fluorescent fragment analysis in 199 patients with ALS (17 familial, 182 sporadic) and 136 healthy controls. We also obtained blood from patients with ALS4 for evaluation of repeats surrounding the SETX gene locus. C9orf72 expansions were evaluated in parallel. RESULTS: Expansions of G4C2 repeats in C9orf72 explained 8.8% of sporadic and 47% of familial ALS cases analyzed. Repeat variance was observed at one other locus, RGS14, but no large expansions were observed, and repeat sizes were not different between cases and controls. No G4C2 repeat expansions were identified at other ALS or FTD risk loci or in ALS4 cases. CONCLUSIONS: G4C2 expansions near known ALS and FTD loci other than C9orf72 are not a common cause of ALS. PMID- 27274541 TI - Biochemical characteristics of AtFAR2, a fatty acid reductase from Arabidopsis thaliana that reduces fatty acyl-CoA and -ACP substrates into fatty alcohols. AB - Fatty alcohols and derivatives are important for proper deposition of a functional pollen wall. Mutations in specific genes encoding fatty acid reductases (FAR) responsible for fatty alcohol production cause abnormal development of pollen. A disrupted AtFAR2 (MS2) gene in Arabidopsis thaliana results in pollen developing an abnormal exine layer and a reduced fertility phenotype. AtFAR2 has been shown to be targeted to chloroplasts and in a purified form to be specific for acyl-ACP substrates. Here, we present data on the in vitro and in planta characterizations of AtFAR2 from A. thaliana and show that this enzyme has the ability to use both, C16:0-ACP and C16:0-CoA, as substrates to produce C16:0-alcohol. Our results further show that AtFAR2 is highly similar in properties and substrate specificity to AtFAR6 for which in vitro data has been published, and which is also a chloroplast localized enzyme. This suggests that although AtFAR2 is the major enzyme responsible for exine layer functionality, AtFAR6 might provide functional redundancy to AtFAR2. PMID- 27274543 TI - A practical overview of pediatric atopic dermatitis, part 2: triggers and grading. AB - In part 2 of this 3-part series on atopic dermatitis (AD) in children, triggers for the appearance and flaring of AD are reviewed. The role of AD in the atopic march is explored. Furthermore, the usage of grading systems in the development of therapeutics and in clinical care is discussed. The natural history of AD has changed from improvement to 50% persistence and therefore it is important to council guardians and patients accordingly. PMID- 27274544 TI - The impact of fellowship training on scholarly productivity in academic dermatology. AB - An increasing number of dermatology residents are pursuing postresidency fellowships to augment their knowledge in dermatology subspecialties. The purpose of this study was to determine whether fellowship training affects the scholarly impact of academic dermatologists, as measured by the h-index. A secondary objective was to compare scholarly productivity among different dermatology subspecialties. Overall, fellowship training is associated with increased scholarly impact; however, when stratifying for academic rank and years of publication activity, this difference does not exist. PMID- 27274545 TI - Lupus erythematosus and localized scleroderma coexistent at the same sites: a rare presentation of overlap syndrome of connective-tissue diseases. AB - Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids. PMID- 27274546 TI - Merkel cell carcinoma in a vein graft donor site. AB - The development of malignancies in graft donor sites is rare and may be caused by de novo malignancies as well as metastatic and iatrogenic spread. Malignancies in graft donor sites are distinguished from Marjolin ulcers by some investigators because they occur in healed surgical wounds rather than in chronic wounds or unstable scars and tend to occur sooner after injury. We present a unique case of Merkel cell carcinoma (MCC) developing in a vein graft donor site 18 years after vein harvesting. PMID- 27274547 TI - Erythematous atrophic plaque in the inguinal fold. PMID- 27274548 TI - Pityriasis lichenoides chronica presenting with bilateral palmoplantar involvement. AB - Pityriasis lichenoides is an uncommon, acquired, idiopathic, self-limiting skin disease that poses a challenge to patients and clinicians to diagnose and treat. Several variants exist including pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis lichenoides chronica (PLC), and febrile ulcer-onecrotic Mucha Habermann disease. Precise classification can be difficult due to an overlap of clinical and histologic features. In this case report we describe a patient with a rare presentation of PLC exhibiting bilateral palmoplantar involvement and mimicking psoriasis. We review the literature and discuss the clinical course, pathogenesis, and current treatment modalities of PLC. PMID- 27274549 TI - Benign lesion on the posterior aspect of the neck. PMID- 27274550 TI - The elongated dermatofibroma: a new dermoscopic variant? PMID- 27274551 TI - Palmoplantar pustular eruption due to dabigatran. PMID- 27274553 TI - Regional lymphomatoid papulosis of the breast restricted to an area of prior radiotherapy. AB - We report the case of a 59-year-old woman with type A regional lymphomatoid papulosis (LyP) that was localized to the left breast, a cutaneous area that had received radiotherapy for treatment of a carcinoma of the breast 5 years prior. This report is a rare example of regional LyP with all lesions located in an area of prior radiotherapy. PMID- 27274552 TI - If a chronic wound does not heal, biopsy it: a clinical lesson on underlying malignancies. PMID- 27274554 TI - Onychomadesis following hand-foot-and-mouth disease. PMID- 27274555 TI - DRESS syndrome with autoimmune hepatitis from strontium ranelate. AB - Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a severe, acute, potentially fatal, multisystem adverse drug reaction characterized by skin rash, fever, hematological abnormalities, and lymphadenopathy with involvement of several internal organs. We report the case of a woman who developed DRESS syndrome with a generalized maculopapular rash, eosinophilia, dyspnea, bilateral cervical lymphadenopathy, and reactivation of Epstein-Barr virus (EBV) with liver damage 3 weeks after administration of strontium ranelate for postmenopausal osteoporosis. Approximately 6 months after total remission of cutaneous symptoms, the patient developed autoimmune hepatitis. This case confirms that strontium ranelate should be considered as a possible factor in the etiopathology of DRESS syndrome as well as in the subsequent development of autoimmune hepatitis. The possibility of developing autoimmune hepatitis as a part of DRESS syndrome related to strontium ranelate use can occur months after the acute episode. PMID- 27274556 TI - Management of vitiligo patients with surgical interventions. AB - Vitiligo is an acquired depigmentation disorder of unknown etiology. Medical treatments are usually reasonably effective for nonstable vitiligo patches; however, for vitiligo patches that have been stable for a substantial period of time, surgical intervention should be considered. In this article, surgical interventions for vitiligo are reviewed, including split-thickness skin grafting, suction blister grafting, miniature punch grafting, and cultured melanocyte transplantation. PMID- 27274557 TI - Growing subcutaneous mass on the thigh. PMID- 27274558 TI - Irregular, smooth, pink plaque on the back. PMID- 27274559 TI - Materials for use in dental CAD/CAM technology--spoiled for choice or a wellspring of new possibilities? PMID- 27274560 TI - Comparison of fracture loads of CAD/CAM and conventionally fabricated temporary fixed dental prostheses after different aging regimens. AB - This study evaluated the fracture loads of different threeunit fixed dental prostheses (FDPs) for temporary restorations. In total, three CAD/CAM materials (VITA CADTemp [CT], Telio CAD [TC], and ZENO ProFix [ZP]) and two chairside materials (Protemp 4 [PT], and Dentalon Plus [DP]) were used for the fabrication of the FDPs. Sixteen FDPs were fabricated from each material in an anatomical shape and stored in 0.9% NaCl solution at 37 degrees C for 14 days. Thereafter, one half of the specimens from each group (n = 8) were additionally mechanically and thermally loaded (240,000 chewing cycles, 50 N, 5 degrees /55 degrees C, 2,100 thermal cycles). Fracture loads were measured and data analyzed using two- and one-way ANOVA, followed by Scheffe's post hoc test. ZP showed the highest mean fracture loads, regardless of the aging regime. Significantly lowest values were identified for DP and TC within the non-thermal loaded group, and for PT and CT within the thermal loaded group. No negative impact of aging regimes could be observed. PMID- 27274561 TI - Understanding dental CAD/CAM for restorations--dental milling machines from a mechanical engineering viewpoint. Part B: labside milling machines. AB - Nowadays, dental numerical controlled (NC) milling machines are available for dental laboratories (labside solution) and dental production centers. This article provides a mechanical engineering approach to NC milling machines to help dental technicians understand the involvement of technology in digital dentistry practice. The technical and economic criteria are described for four labside and two production center dental NC milling machines available on the market. The technical criteria are focused on the capacities of the embedded technologies of milling machines to mill prosthetic materials and various restoration shapes. The economic criteria are focused on investment cost and interoperability with third party software. The clinical relevance of the technology is discussed through the accuracy and integrity of the restoration. It can be asserted that dental production center milling machines offer a wider range of materials and types of restoration shapes than labside solutions, while labside solutions offer a wider range than chairside solutions. The accuracy and integrity of restorations may be improved as a function of the embedded technologies provided. However, the more complex the technical solutions available, the more skilled the user must be. Investment cost and interoperability with third-party software increase according to the quality of the embedded technologies implemented. Each private dental practice may decide which fabrication option to use depending on the scope of the practice. PMID- 27274562 TI - The effect of immediate dentin sealing and optical powder removal method on the fracture resistance of CAD/CAM-fabricated endocrowns. AB - OBJECTIVES: To evaluate the effect of immediate dentin sealing and optical powder removal method on the fracture resistance of CAD/CAM-fabricated ceramic endocrowns. MATERIALS AND METHODS: Seventy-eight extracted premolars were endodontically treated. Standardized endocrown preparations were done in 60 teeth. Teeth were divided equally (n = 10) depending on the treatment of dentin (delayed sealing [DS] or immediate sealing [IS]), and the methods of optical powder removal (air-water spray washing [AW]; microabrasion [MA]; or aqueous suspension of pumice [PB], followed by air-water spray washing). After cementation, specimens were thermocycled (5,000 cycles, 5 degrees C/50 degrees C) and stored in distilled water for 1 week. Specimens were loaded in compression using a universal testing machine until failure. Failure load was recorded, and modes of failure were examined under a stereomicroscope. Micromorphological evaluation of different dentin treatments was done under SEM (n = 3). Results were analyzed using two-way ANOVA and Bonferroni post hoc multiple comparison tests (alpha = 0.05). RESULTS: Fracture resistance of all IS groups was significantly lower than DS groups, except for AW. There was no statistically significant difference between powder removal methods. CONCLUSION: Immediate dentin sealing does not improve the fracture resistance of endocrown restorations. Air-water spray washing is adequate to remove the optical powder after optical scanning impression taking. PMID- 27274563 TI - Science beyond fiction. A revolution of knowledge transfer in research, education, and practice is on the horizon. AB - "Digitality" (as opposed to "digitalization"--the conversion from the analog domain to the digital domain) will open up a whole new world that does not originate from the analog world. Contemporary research in the field of neural concepts and neuromorphic computing systems will lead to convergences between the world of digitality and the world of neuronality, giving the theme "Knowledge and Culture" a new meaning. The simulation of virtual multidimensional and contextual spaces will transform the transfer of knowledge from a uni- and bidirectional process into an interactive experience. We will learn to learn in a ubiquitous computing environment and will abandon conventional curriculum organization principles. The adaptation of individualized ontologies will result in the emergence of a new world of knowledge in which knowledge evolves from a cultural heritage into a commodity. PMID- 27274564 TI - Microveneering technique for esthetic enhancement of monolithic zirconia restorations. AB - The importance of monolithic ceramic restorations is growing, given the safe and cost-effective options for fabrication of such dental crowns and fixed dental prostheses. The optical characteristics of traditional zirconia do not suffice for this purpose. Improved restorative materials that can achieve satisfactory results in posterior restorations have been proposed to solve the problem. In the anterior region, however, even "esthetic" zirconia ceramic is unable to attain results comparable to those of glass-ceramic. Microveneering is a simple, reliable, and timesaving solution. Minimal reduction and veneering can significantly improve the results. A characteristic case is presented here. PMID- 27274565 TI - A rigorous detection of interstellar CH3NCO: An important missing species in astrochemical networks. AB - The recent analysis of the composition of the frozen surface of comet 67P/Churyumov-Gerasimenko has revealed a significant number of complex organic molecules. Methyl isocyanate (CH3NCO) is one of the more abundant species detected on the comet surface. In this work we report extensive characterization of its rotational spectrum resulting in a list of 1269 confidently assigned laboratory lines and its detection in space towards the Orion clouds where 399 lines of the molecule have been unambiguously identified. We find that the limited mm-wave laboratory data reported prior to our work require some revision. The abundance of CH3NCO in Orion is only a factor of ten below those of HNCO and CH3CN. Unlike the molecular abundances in the coma of comets, which correlate with those of warm molecular clouds, molecular abundances in the gas phase in Orion are only weakly correlated with those measured on the comet surface. We also compare our abundances with those derived recently for this molecule towards Sgr B2 (Halfen et al. 2015). A more accurate abundance of CH3NCO is provided for this cloud based on our extensive laboratory work. PMID- 27274566 TI - Advancing Translation and Dissemination Research and Practice Through the Physical Activity Policy Research Network Plus. PMID- 27274567 TI - Apparatus to measure the vapor pressure of slowly decomposing compounds from 1 Pa to 105 Pa. AB - This article describes an apparatus and method for measuring vapor pressures in the range from 1 Pa to 105 Pa. Its three distinctive elements are : (1) the static pressure measurements were made with only a small temperature difference between the vapor and the condensed phase, (2) the sample was degassed in situ, and (3) the temperature range extended up to 200 degrees C. The apparatus was designed to measure metal-organic precursors, which often are toxic, pyrophoric, or unstable. Vapor pressures are presented for naphthalene, ferrocene, diethyl phthalate, and TEMAH (tetrakisethylmethylaminohafnium). Also presented are data for the temperature-dependent decomposition rate of TEMAH. PMID- 27274568 TI - Taxes and Bribes in Uganda. AB - Using data from 433 firms operating along Uganda's charcoal and timber supply chains we investigate patterns of bribe payment and tax collection between supply chain actors and government officials responsible for collecting taxes and fees. We examine the factors associated with the presence and magnitude of bribe and tax payments using a series of bivariate probit and Tobit regression models. We find empirical support for a number of hypotheses related to payments, highlighting the role of queuing, capital-at-risk, favouritism, networks, and role in the supply chain. We also find that taxes crowd-in bribery in the charcoal market. PMID- 27274569 TI - Marital Conflict in Older Couples: Positivity, Personality, and Health. AB - We examine the implications of health and personality characteristics for late life marital conflict, using data from the 2010-11 wave of the National Social Life Health and Aging Project (NSHAP), a nationally representative study with data on both partners in 955 marital and cohabitational dyads. Using these data, we relate characteristics of husbands to characteristics of their wives, and vice versa. Wives with husbands in fair or poor physical health are more likely to report high levels of marital conflict, but the reverse is not true. Similarly, wives report more conflict when their husbands are high on Neuroticism, high on Extraversion, and low on a new measure we call Positivity. Our findings point to noteworthy gender differences between men and women in the associations between individual characteristics and levels of marital conflict. We point to differences between husbands' and wives' marital roles as a contributor to these differences. PMID- 27274570 TI - Spot size variation FCS in simulations of the 2D Ising model. AB - Spot variation fluorescence correlation spectroscopy (svFCS) was developed to study the movement and organization of single molecules in plasma membranes. This experimental technique varies the size of an illumination area while measuring correlations in time using standard fluorescence correlation methods. Frequently, this data is interpreted using the assumption that correlation measurements reflect the dynamics of single molecule motions, and not motions of the average composition. Here, we explore how svFCS measurements report on the dynamics of components diffusing within simulations of a 2D Ising model with a conserved order parameter. Simulated correlation functions report on both the fast dynamics of single component mobility and the slower dynamics of the average composition. Over a range of simulation conditions, a conventional svFCS analysis suggests the presence of anomalous diffusion even though single molecule motions are nearly Brownian in these simulations. This misinterpretation is most significant when the surface density of the fluorescent label is elevated, therefore we suggest future measurements be made over a range of tracer densities. Some simulation conditions reproduce qualitative features of published svFCS experimental data. Overall, this work emphasizes the need to probe membranes using multiple complimentary experimental methodologies in order to draw conclusions regarding the nature of spatial and dynamical heterogeneity in these systems. PMID- 27274571 TI - Internet Effects in Times of Political Crisis: Online Newsgathering and Attitudes toward the European Union. AB - This paper evaluates the influence of online news consumption on attitudes toward the European Union in a context of protracted economic crisis. Using data from the 2011 Irish National Election Study, we combine location-specific information on broadband availability with respondent geo-location data, which facilitates causal inference about the effects of online news consumption via instrumental variable models. Results show that Irish citizens who source political information online are more prone to blame the EU for the poor state of the economy than those who do not. There is evidence of preference reinforcement among those with negative predispositions toward the EU, but not among pro-EU citizens. We complement this analysis with a study of voting behavior in the European Fiscal Compact Referendum, employing a similar methodological approach. The results from this second survey confirm the anti-EU influence of online news consumption among Irish citizens, although evidence suggests a pro-EU effect among voters who browsed the website of the politically neutral Irish Referendum Commission. Our paper contributes to the literature on public opinion, the EU, and political attitudes in times of crisis. PMID- 27274572 TI - Democracy's Denominator: Reassessing Responsiveness with Public Opinion on the National Policy Agenda. AB - Democratic responsiveness concerns the degree to which government policies match public preferences. Responsiveness studies typically use national surveys to characterize public opinion, but whether poll questions overlap with the policy agenda is unknown. The first of two empirical analyses presented here, with hundreds of issues on the national agenda in the United States from 1947 to 2000, reveals that public opinion is mostly unrelated to policy outcomes. The picture appears to be even more ominous-that is, opinion and policy are negatively related-on highly salient issues that attract media attention. A second study revisiting published work confirms that responsiveness patterns look different depending upon whether studies of opinion-policy connections (a) begin with survey data and then examine policy developments, or (b) begin with national legislative agenda issues and then examine survey data. Thus, conclusions about democratic responsiveness depend upon the issues that are examined, and often opinion surveys do not include questions about tangible public policy options. In that sense, future changes in democratic responsiveness might go undetected because scholars often lack data on what goes into the denominator of democracy. PMID- 27274573 TI - The Anxious and Ambivalent Partisan: The Effect of Incidental Anxiety on Partisan Motivated Recall and Ambivalence. AB - Affective Intelligence Theory (AIT) asserts that anxiety reduces the effect of party identification on candidate preferences (Marcus, Neuman, and MacKuen 2000), but recent studies have raised doubts about this causal claim. Rather than functioning as a moderator of party identification, perhaps anxiety has a direct effect on preferences, or perhaps the relationship is reversed and preferences drive emotions (Ladd and Lenz 2008). Alternatively, Marcus et al.'s measure of anxiety may simply be capturing partisan ambivalence, so the posited relationship is spurious (Lavine, Johnston, and Steenbergen 2012). This paper addresses each of these questions by examining the effect of experimentally induced emotions on the types of considerations that came to mind when a national sample of adult Americans was asked what they liked and disliked about Barack Obama. By directly manipulating anxiety, this experiment avoids the causal ambiguity plaguing this debate and ascertains the true nature of the relationship between anxiety and ambivalence. Consistent with AIT, anxiety led respondents to recall more contemporary considerations, whereas enthusiasm brought to mind more long standing considerations. Because the political context at the time of the study (fall 2013) was a very tumultuous time for the Obama administration, the increased accessibility of contemporary considerations led Democratic participants to experience more ambivalence in the anxiety condition. This effect was concentrated among those Democrats who were exposed to the most newspaper coverage. PMID- 27274574 TI - The Political Consequences of Latino Prejudice against Blacks. AB - A good deal of scholarship examines the effects of prejudice against blacks on public opinion and vote choice in the United States. Despite producing valuable insights, this research largely ignores the attitudes of Latinos-a critical omission, since Latinos constitute a rapidly growing share of the population. Using two nationally representative survey data sets, we find that the level of racial prejudice is comparable for Latinos and non-Hispanic whites. Equally comparable are associations between prejudice and political preferences: policy opinion and support for Obama in the 2008 presidential election. Our findings suggest that despite demographic changes, efforts to enact policies intended to assist blacks and elect black candidates will continue to be undermined by prejudice. That said, Latinos are more likely than non-Hispanic whites to support policies intended to assist blacks, because Latinos are more Democratic than non Hispanic whites, more egalitarian, and less committed to the value of limited government. PMID- 27274575 TI - Are Survey Respondents Lying about Their Support for Same-Sex Marriage? Lessons from a List Experiment. AB - Public opinion polls consistently show that a growing majority of Americans support same-sex marriage. Critics, however, raise the possibility that these polls are plagued by social desirability bias, and thereby may overstate public support for gay and lesbian rights. We test this proposition using a list experiment embedded in the 2013 Cooperative Congressional Election Study. List experiments afford respondents an anonymity that allows them to provide more truthful answers to potentially sensitive survey items. Our experiment finds no evidence that social desirability is affecting overall survey results. If there is social desirability in polling on same-sex marriage, it pushes in both directions. Indeed, our efforts provide new evidence that a national opinion majority favors same-sex marriage. To evaluate the robustness of our findings, we analyze a second list experiment, this one focusing on the inclusion of sexual orientation in employment nondiscrimination laws. Again, we find no overall evidence of bias. PMID- 27274576 TI - Reliability Concerns in Measuring Respondent Skin Tone by Interviewer Observation. AB - The current study assesses the intercoder reliability of one of the most important skin tone measurement instruments-the Massey-Martin scale. This scale is used in several high-profile social surveys, but has not yet been psychometrically evaluated. The current evaluation is only possible because, for the first time, the General Social Survey's 2010-2014 panel used the instrument to guide interviewers' skin tone observation of the same respondents in two different years (2012 and 2014). Despite the widespread use of the Massey-Martin scale to investigate potential effects of skin tone on social attitudes and outcomes, the data suggest that the measure has low intercoder reliability. Implications for researchers and survey practitioners are discussed. PMID- 27274577 TI - Breaking Out of the Lab: Measuring Real-Time Responses to Televised Political Content in Real-World Settings. AB - Real-time response (RTR) measurement is an important technique for analyzing human processing of electronic media stimuli. Although it has been demonstrated that RTR data are reliable and internally valid, some argue that they lack external validity. The reason for this is that RTR measurement is restricted to a laboratory environment due to its technical requirements. This paper introduces a smartphone app that 1) captures real-time responses using the dial technique and 2) provides a solution for one of the most important problems in RTR measurement, the (automatic) synchronization of RTR data. In addition, it explores the reliability and validity of mobile RTR measurement by comparing the real-time reactions of two samples of young and well-educated voters to the 2013 German televised debate. Whereas the first sample participated in a classical laboratory study, the second sample was equipped with our mobile RTR system and watched the debate at home. Results indicate that the mobile RTR system yields similar results to the lab-based RTR measurement, providing evidence that laboratory studies using RTR are externally valid. In particular, the argument that the artificial reception situation creates artificial results has to be questioned. In addition, we conclude that RTR measurement outside the lab is possible. Hence, mobile RTR opens the door for large-scale studies to better understand the processing and impact of electronic media content. PMID- 27274578 TI - Numeracy and the Persuasive Effect of Policy Information and Party Cues. AB - Numeric political appeals represent a prevalent but overlooked domain of public opinion research. When can quantitative information change political attitudes, and is this change trumped by partisan effects? We analyze how numeracy-or individual differences in citizens' ability to process and apply numeric policy information-moderates the effectiveness of numeric political appeals on a moderately salient policy issue. Results show that those low in numeracy exhibit a strong party-cue effect, treating numeric information in a superficial and heuristic fashion. Conversely, those high in numeracy are persuaded by numeric information, even when it is sponsored by the opposing party, overcoming the party-cue effect. Our results make clear that overlooking numeric ability when analyzing quantitative political appeals can mask significant persuasion effects, and we build on recent work advancing the understanding of individual differences in public opinion. PMID- 27274579 TI - Cross-National Trends in Religious Service Attendance. AB - The nature of religious change and the future of religion have been central questions of social science since its inception. But empirical research on this question has been quite American-centric, encouraged by the conventional wisdom that the United States is an outlier of religiosity in the developed world, and, more pragmatically, by the availability of survey data. The dramatic growth in the number and reach of cross-national surveys over the past two decades has offered a corrective. These data have allowed research on religious trends in the United States, Canada, and Europe, putting American trends into comparative relief. This research synthesis reviews the past quarter century of cross national comparative survey research on religious behavior, focusing on religious service attendance as a commonly measured behavior that is arguably more equivalent across societies and cultures than other measures of religiosity. The lack of evidence for religious revival is highlighted, noting instead declining rates of attendance in the United States and Canada, and either declining rates or low "bottomed-out" stability in Western Europe, most of Eastern Europe, and Australia and New Zealand. Finally, countries in Latin America, Africa, and Asia are discussed to the extent that research allows, before a call for future research-in these places in particular-is made in order to correct for the Western and Christian focus of much of the research on cross-national religious trends. PMID- 27274580 TI - Manuscript Referees, 2015. PMID- 27274586 TI - Progress in Kdo-glycoside chemistry. AB - Glycosylation chemistry of 3-deoxy-D-manno-oct-2-ulosonic acid units has been considerably developed within the last decade. This review covers major achievements with respect to improved yields and anomeric selectivity as well as suppression of the elimination side reaction via selection of dedicated protecting groups and appropriate activation of the anomeric center. PMID- 27274585 TI - The Trans-Contextual Model of Autonomous Motivation in Education: Conceptual and Empirical Issues and Meta-Analysis. AB - The trans-contextual model outlines the processes by which autonomous motivation toward activities in a physical education context predicts autonomous motivation toward physical activity outside of school, and beliefs about, intentions toward, and actual engagement in, out-of-school physical activity. In the present article, we clarify the fundamental propositions of the model and resolve some outstanding conceptual issues, including its generalizability across multiple educational domains, criteria for its rejection or failed replication, the role of belief-based antecedents of intentions, and the causal ordering of its constructs. We also evaluate the consistency of model relationships in previous tests of the model using path-analytic meta-analysis. The analysis supported model hypotheses but identified substantial heterogeneity in the hypothesized relationships across studies unattributed to sampling and measurement error. Based on our meta-analysis, future research needs to provide further replications of the model in diverse educational settings beyond physical education and test model hypotheses using experimental methods. PMID- 27274588 TI - Defining the syndrome associated with congenital Zika virus infection. PMID- 27274589 TI - Charting a path to end the AIDS epidemic. PMID- 27274590 TI - Public health round-up. PMID- 27274591 TI - Fake lifejackets play a role in drowning of refugees. AB - Fake lifejackets are one of the hazards refugees face when they risk their lives to cross the sea to Europe. Menelaos Tzafalias reports from the Greek island of Lesbos. PMID- 27274592 TI - The big causes of death from noncommunicable disease. AB - Richard Peto tells Andreia Azevedo Soares why efforts to reduce premature death from noncommunicable diseases should focus mainly on the big causes. PMID- 27274593 TI - The role of the law in reducing tuberculosis transmission in Botswana, South Africa and Zambia. AB - OBJECTIVE: To determine whether laws and regulations in Botswana, South Africa and Zambia - three countries with a high tuberculosis and HIV infection burden - address elements of the World Health Organization (WHO) policy on tuberculosis infection control. METHODS: An online desk review of laws and regulations that address six selected elements of the WHO policy on tuberculosis infection control in the three countries was conducted in November 2015 using publicly available domestic legal databases. The six elements covered: (i) national policy and legal framework; (ii) health facility design, construction and use; (iii) tuberculosis disease surveillance among health workers; (iv) patients' and health workers' rights; (v) monitoring of infection control measures; and (vi) relevant research. FINDINGS: The six elements were found to be adequately addressed in the three countries' laws and regulations. In all three, tuberculosis case-reporting is required, as is tuberculosis surveillance among health workers. Each country's legal and regulatory framework also addresses the need to respect individuals' rights and privacy while safeguarding public health. These laws and regulations create a strong foundation for tuberculosis infection control. Although the legal and regulatory frameworks thoroughly address tuberculosis infection control, their dissemination, implementation and enforcement were not assessed, nor was their impact on public health. CONCLUSION: Laws and regulations in Botswana, South Africa and Zambia address all six selected elements of the WHO policy on tuberculosis infection control. However, the lack of data on their implementation is a limitation. Future research should assess the implementation and public health impact of laws and regulations. PMID- 27274594 TI - Recommendations for dealing with waste contaminated with Ebola virus: a Hazard Analysis of Critical Control Points approach. AB - OBJECTIVE: To assess, within communities experiencing Ebola virus outbreaks, the risks associated with the disposal of human waste and to generate recommendations for mitigating such risks. METHODS: A team with expertise in the Hazard Analysis of Critical Control Points framework identified waste products from the care of individuals with Ebola virus disease and constructed, tested and confirmed flow diagrams showing the creation of such products. After listing potential hazards associated with each step in each flow diagram, the team conducted a hazard analysis, determined critical control points and made recommendations to mitigate the transmission risks at each control point. FINDINGS: The collection, transportation, cleaning and shared use of blood-soiled fomites and the shared use of latrines contaminated with blood or bloodied faeces appeared to be associated with particularly high levels of risk of Ebola virus transmission. More moderate levels of risk were associated with the collection and transportation of material contaminated with bodily fluids other than blood, shared use of latrines soiled with such fluids, the cleaning and shared use of fomites soiled with such fluids, and the contamination of the environment during the collection and transportation of blood-contaminated waste. CONCLUSION: The risk of the waste-related transmission of Ebola virus could be reduced by the use of full personal protective equipment, appropriate hand hygiene and an appropriate disinfectant after careful cleaning. Use of the Hazard Analysis of Critical Control Points framework could facilitate rapid responses to outbreaks of emerging infectious disease. PMID- 27274595 TI - A tuberculosis nationwide prevalence survey in Gambia, 2012. AB - OBJECTIVE: To estimate the population prevalence of active pulmonary tuberculosis in Gambia. METHODS: Between December 2011 and January 2013, people aged >= 15 years participating in a nationwide, multistage cluster survey were screened for active pulmonary tuberculosis with chest radiography and for tuberculosis symptoms. For diagnostic confirmation, sputum samples were collected from those whose screening were positive and subjected to fluorescence microscopy and liquid tuberculosis cultures. Multiple imputation and inverse probability weighting were used to estimate tuberculosis prevalence. FINDINGS: Of 100 678 people enumerated, 55 832 were eligible to participate and 43 100 (77.2%) of those participated. A majority of participants (42 942; 99.6%) were successfully screened for symptoms and by chest X-ray. Only 5948 (13.8%) were eligible for sputum examination, yielding 43 bacteriologically confirmed, 28 definite smear-positive and six probable smear-positive tuberculosis cases. Chest X-ray identified more tuberculosis cases (58/69) than did symptoms alone (43/71). The estimated prevalence of smear-positive and bacteriologically confirmed pulmonary tuberculosis were 90 (95% confidence interval, CI: 53-127) and 212 (95% CI: 152 272) per 100 000 population, respectively. Tuberculosis prevalence was higher in males (333; 95% CI: 233-433) and in the 35-54 year age group (355; 95% CI: 219 490). CONCLUSION: The burden of tuberculosis remains high in Gambia but lower than earlier estimates of 490 per 100 000 population in 2010. Less than half of all cases would have been identified based on smear microscopy results alone. Successful control efforts will require interventions targeting men, increased access to radiography and more accurate, rapid diagnostic tests. PMID- 27274596 TI - Vaccination timing of low-birth-weight infants in rural Ghana: a population based, prospective cohort study. AB - OBJECTIVE: To investigate delays in first and third dose diphtheria-tetanus pertussis (DTP1 and DTP3) vaccination in low-birth-weight infants in Ghana, and the associated determinants. METHODS: We used data from a large, population-based vitamin A trial in 2010-2013, with 22 955 enrolled infants. We measured vaccination rate and maternal and infant characteristics and compared three categories of low-birth-weight infants (2.0-2.4 kg; 1.5-1.9 kg; and < 1.5 kg) with infants weighing >= 2.5 kg. Poisson regression was used to calculate vaccination rate ratios for DTP1 at 10, 14 and 18 weeks after birth, and for DTP3 at 18, 22 and 24 weeks (equivalent to 1, 2 and 3 months after the respective vaccination due dates of 6 and 14 weeks). FINDINGS: Compared with non-low-birth weight infants (n = 18 979), those with low birth weight (n = 3382) had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio, aRR: 0.58; 95% confidence interval, CI: 0.43-0.77) and at age 18 weeks (aRR: 0.63; 95% CI: 0.50-0.80). Infants weighing 1.5-1.9 kg (n = 386) had vaccination rates approximately 25% lower than infants weighing >= 2.5 kg at these time points. Similar results were observed for DTP3. Lower maternal age, educational attainment and longer distance to the nearest health facility were associated with lower DTP1 and DTP3 vaccination rates. CONCLUSION: Low-birth-weight infants are a high-risk group for delayed vaccination in Ghana. Efforts to improve the vaccination of these infants are warranted, alongside further research to understand the reasons for the delays. PMID- 27274597 TI - Measuring the adequacy of antenatal health care: a national cross-sectional study in Mexico. AB - OBJECTIVE: To propose an antenatal care classification for measuring the continuum of health care based on the concept of adequacy: timeliness of entry into antenatal care, number of antenatal care visits and key processes of care. METHODS: In a cross-sectional, retrospective study we used data from the Mexican National Health and Nutrition Survey (ENSANUT) in 2012. This contained self reported information about antenatal care use by 6494 women during their last pregnancy ending in live birth. Antenatal care was considered to be adequate if a woman attended her first visit during the first trimester of pregnancy, made a minimum of four antenatal care visits and underwent at least seven of the eight recommended procedures during visits. We used multivariate ordinal logistic regression to identify correlates of adequate antenatal care and predicted coverage. FINDINGS: Based on a population-weighted sample of 9 052 044, 98.4% of women received antenatal care during their last pregnancy, but only 71.5% (95% confidence interval, CI: 69.7 to 73.2) received maternal health care classified as adequate. Significant geographic differences in coverage of care were identified among states. The probability of receiving adequate antenatal care was higher among women of higher socioeconomic status, with more years of schooling and with health insurance. CONCLUSION: While basic antenatal care coverage is high in Mexico, adequate care remains low. Efforts by health systems, governments and researchers to measure and improve antenatal care should adopt a more rigorous definition of care to include important elements of quality such as continuity and processes of care. PMID- 27274598 TI - Priority-setting for achieving universal health coverage. AB - Governments in low- and middle-income countries are legitimizing the implementation of universal health coverage (UHC), following a United Nation's resolution on UHC in 2012 and its reinforcement in the sustainable development goals set in 2015. UHC will differ in each country depending on country contexts and needs, as well as demand and supply in health care. Therefore, fundamental issues such as objectives, users and cost-effectiveness of UHC have been raised by policy-makers and stakeholders. While priority-setting is done on a daily basis by health authorities - implicitly or explicitly - it has not been made clear how priority-setting for UHC should be conducted. We provide justification for explicit health priority-setting and guidance to countries on how to set priorities for UHC. PMID- 27274599 TI - How can health ministries present persuasive investment plans for women's, children's and adolescents' health? AB - Most low- and middle-income countries face financing pressures if they are to adequately address the recommendations of the Global Strategy for Women's, Children's and Adolescent's Health. Negotiations between government ministries of health and finance are a key determinant of the level and effectiveness of public expenditure in the health sector. Yet ministries of health in low- and middle income countries do not always have a good record in obtaining additional resources from key decision-making institutions. This is despite the strong evidence about the affordability and cost-effectiveness of many public health interventions and of the economic returns of investing in health. This article sets out 10 attributes of effective budget requests that can address the analytical needs and perspectives of ministries of finance and other financial decision-makers. We developed the list based on accepted economic principles, a literature review and a workshop in June 2015 involving government officials and other key stakeholders from low- and middle-income countries. The aim is to support ministries of health to present a more strategic and compelling plan for investments in the health of women, children and adolescents. PMID- 27274600 TI - Scale-up of integrated malaria vector control: lessons from Malawi. AB - PROBLEM: Indoor residual spraying and long-lasting insecticidal nets (LLINs) are key tools for malaria vector control. Malawi has struggled to scale up indoor residual spraying and to improve LLIN coverage and usage. APPROACH: In 2002, the Malawian National Malaria Control Programme developed guidelines for insecticide treated net distribution to reach the strategic target of at least 60% coverage of households with an LLIN. By 2005, the target coverage was 80% of households and the Global Fund financed the scale-up. The US President's Malaria Initiative funded the indoor residual spraying intervention. LOCAL SETTING: Malawi's entire population is considered to be at risk of malaria. Poor vector control, insecticide resistance in malaria vectors and insufficient technical and financial support have exacerbated the malaria burden. RELEVANT CHANGES: Between 2002 and 2012, 18 248 206 LLINs had been distributed. The coverage of at least one LLIN per household increased from 27% (3689/13 664) to 58% (1974/3404). Indoor residual spraying coverage increased from 28 227 to 653 592 structures between 2007 and 2011. However, vector resistance prompted a switch from pyrethroids to organophosphates for indoor residual spraying, which increased the cost and operations needed to be cut back from seven to one district. Malaria cases increased from 2 853 315 in 2002 to 6 748 535 in 2010, and thereafter dropped to 4 922 596 in 2012. LESSONS LEARNT: A single intervention-based approach for vector control may have suboptimal impact. Well-coordinated integrated vector management may offer greater benefits. A resistance management plan is essential for effective and sustainable vector control. PMID- 27274602 TI - Recommended Protocol for Round Robin Studies in Additive Manufacturing. AB - One way to improve confidence and encourage proliferation of additive manufacturing (AM) technologies and parts is by generating more high quality data describing the performance of AM processes and parts. Many in the AM community see round robin studies as a way to generate large data sets while distributing the cost among the participants, thereby reducing the cost to individual users. The National Institute of Standards and Technology (NIST) has conducted and participated in several of these AM round robin studies. While the results of these studies are interesting and informative, many of the lessons learned in conducting these studies concern the logistics and methods of the study and unique issues presented by AM. Existing standards for conducting interlaboratory studies of measurement methods, along with NIST's experience, form the basis for recommended protocols for conducting AM round robin studies. The role of round robin studies in AM qualification, some of the limitations of round robin studies, and the potential benefit of less formal collaborative experiments where multiple factors, AM machine being only one, are varied simultaneously are also discussed. PMID- 27274601 TI - Bayesian regression analysis of data with random effects covariates from nonlinear longitudinal measurements. AB - Joint models for a wide class of response variables and longitudinal measurements consist on a mixed-effects model to fit longitudinal trajectories whose random effects enter as covariates in a generalized linear model for the primary response. They provide a useful way to assess association between these two kinds of data, which in clinical studies are often collected jointly on a series of individuals and may help understanding, for instance, the mechanisms of recovery of a certain disease or the efficacy of a given therapy. When a nonlinear mixed effects model is used to fit the longitudinal trajectories, the existing estimation strategies based on likelihood approximations have been shown to exhibit some computational efficiency problems (De la Cruz et al., 2011). In this article we consider a Bayesian estimation procedure for the joint model with a nonlinear mixed-effects model for the longitudinal data and a generalized linear model for the primary response. The proposed prior structure allows for the implementation of an MCMC sampler. Moreover, we consider that the errors in the longitudinal model may be correlated. We apply our method to the analysis of hormone levels measured at the early stages of pregnancy that can be used to predict normal versus abnormal pregnancy outcomes. We also conduct a simulation study to assess the importance of modelling correlated errors and quantify the consequences of model misspecification. PMID- 27274603 TI - Atomic Detail Visualization of Photosynthetic Membranes with GPU-Accelerated Ray Tracing. AB - The cellular process responsible for providing energy for most life on Earth, namely photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. We describe the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers. PMID- 27274604 TI - Photon counting imaging and centroiding with an electron-bombarded CCD using single molecule localisation software. AB - Photon event centroiding in photon counting imaging and single-molecule localisation in super-resolution fluorescence microscopy share many traits. Although photon event centroiding has traditionally been performed with simple single-iteration algorithms, we recently reported that iterative fitting algorithms originally developed for single-molecule localisation fluorescence microscopy work very well when applied to centroiding photon events imaged with an MCP-intensified CMOS camera. Here, we have applied these algorithms for centroiding of photon events from an electron-bombarded CCD (EBCCD). We find that centroiding algorithms based on iterative fitting of the photon events yield excellent results and allow fitting of overlapping photon events, a feature not reported before and an important aspect to facilitate an increased count rate and shorter acquisition times. PMID- 27274605 TI - A Newly Developed Tri-Leaflet Polymeric Heart Valve Prosthesis. AB - The potential of polymeric heart valves (PHV) prostheses is to combine the hemodynamic performances of biological valves with the durability of mechanical valves. The aim of this work is to design and develop a new tri-leaflet prosthetic heart valve (HV) made from styrenic block copolymers. A computational finite element model was implemented to optimize the thickness of the leaflets, to improve PHV mechanical and hydrodynamic performances. Based on the model outcomes, 8 prototypes of the designed valve were produced and tested in vitro under continuous and pulsatile flow conditions, as prescribed by ISO 5840 Standard. A specially designed pulse duplicator allowed testing the PHVs at different flow rates and frequency conditions. All the PHVs met the requirements specified in ISO 5840 Standard in terms of both regurgitation and effective orifice area (EOA), demonstrating their potential as HV prostheses. PMID- 27274606 TI - Classroom and Teacher Support in Kindergarten: Associations with the Behavioral and Academic Adjustment of Low-Income Students. AB - For socio-economically disadvantaged children, a positive experience in kindergarten may play a particularly important role in fostering the behavioral adjustment and learning engagement necessary for school success. Prior research has identified supportive student-teacher relationships and classroom emotional support as two features of the classroom context that can promote student adjustment; however, very few studies have examined these two aspects of the classroom context simultaneously. Given their modest inter-correlations, these dimensions of classroom context may have both unique and shared associations with child progress. This study followed 164 children as they transitioned from Head Start into elementary school, and regressions revealed significant unique associations between each type of kindergarten support and children's aggressive behaviors, social withdrawal, learning engagement, and emergent literacy skills in first grade, controlling for their pre-kindergarten adjustment. In addition, learning engagement significantly mediated the association between a supportive relationship with the kindergarten teacher and first grade literacy skills. PMID- 27274607 TI - Electrical detection of specific versus non-specific binding events in breast cancer cells. AB - Detection of circulating tumor cells (CTCs) from patient blood samples offers a desirable alternative to invasive tissue biopsies for screening of malignant carcinomas. A rigorous CTC detection method must identify CTCs from millions of other formed elements in blood and distinguish them from healthy tissue cells also present in the blood. CTCs are known to overexpress certain surface receptors, many of which aid them in invading other tissue, and these provide an avenue for their detection. We have developed carbon nanotube (CNT) thin film devices to specifically detect these receptors in intact cells. The CNT sidewalls are functionalized with antibodies specific to Epithelial Cell Adhesion Molecule (EpCAM), a marker overexpressed by breast and other carcinomas. Specific binding of EpCAM to anti-EpCAM causes a change in the local charge environment of the CNT surface which produces a characteristic electrical signal. Two cell lines are tested in the device: MCF7, a mammary adenocarcinoma line which overexpresses EpCAM, and MCF10A, a non-tumorigenic mammary epithelial line which does not. Introduction of MCF7s causes significant changes in the electrical conductance of the devices due to specific binding and associated charge environment change near the CNT sidewalls. Introduction of MCF10A displays a different profile due to purely nonspecific interactions. The profile of specific vs. nonspecific interaction signatures using carbon based devices will guide development of this diagnostic tool towards clinical sample volumes. PMID- 27274609 TI - The cognitive impact of interactive design features for learning complex materials in medical education. AB - To identify the most effective way for medical students to interact with a browser-based learning module on the symptoms and neurological underpinnings of stroke syndromes, this study manipulated the way in which subjects interacted with a graphical model of the brain and examined the impact of functional changes on learning outcomes. It was hypothesized that behavioral interactions that were behaviorally more engaging and which required deeper consideration of the model would result in heightened cognitive interaction and better learning than those whose manipulation required less deliberate behavioral and cognitive processing. One hundred forty four students were randomly assigned to four conditions whose model controls incorporated features that required different levels of behavioral and cognitive interaction: Movie (low behavioral/low cognitive, n = 40), Slider (high behavioral/low cognitive, n = 36), Click (low behavioral/high cognitive, n = 30), and Drag (high behavioral/high cognitive, n = 38). Analysis of Covariates (ANCOVA) showed that students who received the treatments associated with lower cognitive interactivity (Movie and Slider) performed better on a transfer task than those receiving the module associated with high cognitive interactivity (Click and Drag, partial eta squared = .03). In addition, the students in the high cognitive interactivity conditions spent significantly more time on the stroke locator activity than other conditions (partial eta squared = .36). The results suggest that interaction with controls that were tightly coupled with the model and whose manipulation required deliberate consideration of the model's features may have overtaxed subjects' cognitive resources. Cognitive effort that facilitated manipulation of content, though directed at the model, may have resulted in extraneous cognitive load, impeding subjects in recognizing the deeper, global relationships in the materials. Instructional designers must, therefore, keep in mind that the way in which functional affordances are integrated with the content can shape both behavioral and cognitive processing, and has significant cognitive load implications. PMID- 27274608 TI - Influence of betaS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease. AB - Introduction. Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of the betaS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The betaS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level was p < 0.05. Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p < 0.0001). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu * Bantu/Benin groups; Bantu/Bantu * Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes. PMID- 27274610 TI - Emergency contraception: Knowledge and practice among women and the spouses seeking termination of pregnancy. AB - BACKGROUND: India was one of the first countries to launch a formal family planning program. Initially, the main thrust of the program was on sterilization but subsequently it has got evolved and now the stress is to bring about awareness of contraception and make informed choices. Emergency contraception has been included in its armamentarium. This study was conducted to find out about the awareness among the cases who report for induced abortion. METHODS: A total of 784 willing cases were enrolled in the study; there were no exclusion criteria except unwillingness. A parallel group was also included consisting of their spouses. Information that was being sought about Emergency Contraception (EC) included its knowledge, details of administration, and availability. RESULTS: Of the 784 cases, a large number, 742 (94.6%), underwent first trimester abortion and only 42 (5.3%) underwent second trimester abortion. 286 (36.4%) patients had not used any contraceptive. A large number had used natural methods (35.3%), like lactation, abstinence, or coitus interruptus, and 25.7% had used barrier contraception inconsistently. A very small percentage in both the groups knew about EC; more number of men knew about EC than women. CONCLUSION: Awareness about emergency contraception is low, as reported in many other studies, though it is available for many years. Awareness about contraceptives needs to be improved and emergency contraceptive should be advocated as a backup method. More efforts are required to generate awareness about regular use of effective contraception and emergency contraception if required. PMID- 27274611 TI - A comparative analysis of root surface biomodification with ethylene diamine tetra acetic acid and tetracycline hydrochloride: An in vitro scanning electron microscopic study. AB - BACKGROUND: The outcome of periodontal regenerative therapy depends upon the of the biocompatibility root surfaces to the regenerating periodontal tissues. This in vitro scanning electron microscopic (SEM) study was designed to evaluate and compare the demineralizing efficacy of ethylene diamine tetra acetic acid (EDTA), with that of tetracycline hydrochloride applied on to the mechanically treated root surfaces of periodontally involved tooth. METHODS: Forty specimens were prepared from teeth extracted due to advanced periodontal disease and divided into two groups. The study group was treated with an EDTA solution (pH 7.4) and the control group was treated with a tetracycline hydrochloride solution (pH 1.8). The photomicrographs obtained were assessed for presence of smear layer, number of exposed dentinal tubules, area occupied by tubule orifices along with intertubular surface appearance. The results thus obtained were analyzed statistically. RESULTS: Both EDTA and tetracycline were effective in removing the smear layer and the exposure of the number of dentinal tubules. The diameters of the tubules and thereby the surface area occupied by the tubule orifices in the EDTA treated group were significantly greater than the tetracycline HCL treated group (p < 0.05). CONCLUSION: The EDTA produced better effects than tetracycline by providing more demineralized area and collagen exposure at a neutral pH. PMID- 27274612 TI - To publish and perish: A Faustian bargain or a Hobson's choice. AB - As a matter of career choice, doctors have to choose between becoming an 'academic' or a 'practitioner.' To conduct research and publish articles in scientific journals is compulsory for the academic professional and mostly optional for the latter. The Medical Council of India has revised the eligibility qualifications for medical teachers over the past decade, and has now come out with regulations for streamlining the process of promotion by focusing on scientific papers, apart from clarifying on required experience and qualifications. 'Predatory publishers' are proliferating across the world, exploiting the reach of the Internet, and are enticing naive professionals to publish their research work with them. The pitfalls of paid publishing in such journals may tarnish upcoming careers if doctors are not cautious. For a price, there are many publishers who will process articles without even rudimentary peer review; and for the sake of padding up of the resume, this Faustian bargain may eventually prove detrimental to authors, and thus with their professional credibility at stake, may prove to be a Hobson's choice. It is suggested for authors to make a wise choice and a correct decision when selecting a journal to submit their manuscripts. PMID- 27274613 TI - BUY QUIET INITIATIVE IN THE USA. AB - Noise-induced hearing loss is still considered one of the most common work related illnesses in the United States of America. The U.S. National Institute for Occupational Safety and Health launched a national Buy Quiet campaign to raise awareness of the importance of purchasing quieter equipment. Buy Quiet encourages companies to seek out and demand quieter equipment thus driving the market to design and create quieter products. In the long run, investment in noise controls should be more prevalent as the market demands quieter products. This paradigm occurs as the market for quieter products expands both from the supply side (manufacturers) and the demand side (tool and equipment purchasers). The key to experiencing the reduced costs and increased benefits of Buy Quiet will be to develop partnerships between manufacturers and consumers. To this end, the U.S. National Institute for Occupational Safety and Health continues to work with partners to educate stakeholders about the risks and true costs of noise induced hearing loss, as well as the economic benefits of buying quieter equipment. PMID- 27274614 TI - HOW DOES COMPLEXITY IMPACT EVALUATION? AN INTRODUCTION TO THE SPECIAL ISSUE. PMID- 27274615 TI - STRUCTURAL INEQUALITY AND SOCIAL SUPPORT FOR WOMEN PRISONERS RELEASED TO RURAL COMMUNITIES. AB - Incarceration and community reentry for rural women reflect gendered processes. We draw upon in-depth semi-structured interviews and focus groups to examine the return of women prisoners to underserved rural communities, while attending to the perspectives of their closest social supporters. Our findings underscore the complexity of the reentry process for rural women and its particular impact on their families. We challenge dominant discourses of personal responsibility that detract from the structura violence and injustice shaping reentry experiences for women and their social supporters. We also consider the policy implications of discharge and reentry planning for rural women and their families, as well as strategies to reduce recidivism. PMID- 27274616 TI - Interplay of Orbital and Relativistic Effects in Bismuth Oxyhalides: BiOF, BiOCl, BiOBr, and BiOI. PMID- 27274617 TI - CHARACTERIZATION OF 17 NEW MICROSATELLITE MARKERS FOR THE DINOFLAGELLATE ALEXANDRIUM FUNDYENSE (DINOPHYCEAE), A HARMFUL ALGAL BLOOM SPECIES. AB - Alexandrium fundyense is the toxic marine dinoflagellate responsible for "red tide" events in temperate and sub-arctic waters worldwide. In the Gulf of Maine (GOM) and Bay of Fundy in the Northwest Atlantic, blooms of A. fundyense recur annually, and are associated with major health and ecosystem impacts. In this region, microsatellite markers have been used to investigate genetic structure and gene flow; however, the loci currently available for this species were isolated from populations from Japan and the North Sea, and only a subset are suitable for the analysis of A. fundyense populations in the Northwest Atlantic. To facilitate future studies of A. fundyense blooms, both in this region and globally, we isolated and characterized 17 polymorphic microsatellite loci from 31 isolates collected from the GOM and from the Nauset Marsh System, an estuary on Cape Cod, MA, USA. These loci yielded between two and 15 alleles per locus, with an average of 7.1. Gene diversities ranged from 0.297 to 0.952. We then analyzed these same 31 isolates using previously published markers for comparison. We determined the new markers are sufficiently variable and better suited for the investigation of genetic structure, bloom dynamics, and diversity in the Northwest Atlantic. PMID- 27274618 TI - The Influence of Executive Functioning on Facial and Subjective Pain Responses in Older Adults. AB - Cognitive decline is known to reduce reliability of subjective pain reports. Although facial expressions of pain are generally considered to be less affected by this decline, empirical support for this assumption is sparse. The present study therefore examined how cognitive functioning relates to facial expressions of pain and whether cognition acts as a moderator between nociceptive intensity and facial reactivity. Facial and subjective responses of 51 elderly participants to mechanical stimulation at three intensities levels (50 kPa, 200 kPa, and 400 kPa) were assessed. Moreover, participants completed a neuropsychological examination of executive functioning (planning, cognitive inhibition, and working memory), episodic memory, and psychomotor speed. The results showed that executive functioning has a unique relationship with facial reactivity at low pain intensity levels (200 kPa). Moreover, cognitive inhibition (but not other executive functions) moderated the effect of pressure intensity on facial pain expressions, suggesting that the relationship between pressure intensity and facial reactivity was less pronounced in participants with high levels of cognitive inhibition. A similar interaction effect was found for cognitive inhibition and subjective pain report. Consequently, caution is needed when interpreting facial (as well as subjective) pain responses in individuals with a high level of cognitive inhibition. PMID- 27274619 TI - Trans fatty acids in the Portuguese food market. AB - Consistent evidence exist on the harmful health effects of industrial trans fatty acids (TFA). In order to have accurate data on TFA intake and implement adequate measures to reduce their intake, each country should have updated estimates of TFA content in the diet. The objective of the present study was to provide data on the TFA content in food commercialized in the Portuguese market. The results on the TFA content of 268 samples acquired between October and December 2013 are reported. Samples were categorized as margarines and shortenings (n = 16), spreadable chocolate fats (n = 6), fried potatoes and chips (n = 25), industrial bakery (n = 4), breakfast cereals (n = 3), pastry products (n = 120), seasonings (n = 5), instant soups (n = 5), instant desserts (n = 6), chocolate snacks (n = 4), microwave popcorn (n = 4), cookies, biscuits and wafers (n = 53), and fast food (n = 13), with butter (n = 4) included for comparison purposes. TFA were quantified by gas chromatography. Total TFA content in the fat ranged from 0.06% to 30.2% (average 1.9%), with the highest average values in the "biscuits, wafers and cookies" group (3.4% TFA), followed by the pastry group (2.0%). Fifty samples (19%) had TFA superior to 2% in the fat. These findings highlight there is still much need for improvement in terms of the TFA content in Portuguese foods, particularly in traditional pastry. PMID- 27274622 TI - Modulating the dysregulated migration of pulmonary arterial hypertensive smooth muscle cells with motif mimicking cell permeable peptides. AB - Migration of vascular smooth muscle cells is a key element in remodeling during pulmonary arterial hypertension (PAH). We are observing key alterations in the migratory characteristics of human pulmonary artery smooth muscle cells (HPASMC) isolated from transplanted lungs of subjects with PAH. Using wound migration and barrier removal assays, we demonstrate that the PAH cells migrate under quiescent growth conditions and in the absence of pro-migratory factors such as platelet derived growth factor (PDGF). Under the same conditions, in the absence of PDGF, non-PAH HPASMC show negligible migration. The dysregulated migration initiates, in part, through phosphorylation events signaled through the unstimulated PDGF receptor via focal adhesion kinase (FAK) whose total basal expression and phosphorylation at tyrosine 391 is markedly increased in the PAH cells and is inhibited by a motif mimicking cell-permeable peptide (MMCPP) targeting the Tyr751 region of the PDGF receptor and by imatinib. However, exposure of the PAH cells to PDGF further promotes migration. Inhibition of p21 activated kinases (PAK), LIM kinases (LIMK), c-Jun N-terminal kinases (JNK) and p38 mitogen activated protein kinases (MAPK) reduces both the dysregulated and the PDGF stimulated migration. Immunofluorescence microscopy confirms these observations showing activated JNK and p38 MAPK at the edge of the wound but not in the rest of the culture in the PAH cells. The upstream inhibitors FAK (PF-573228) and imatinib block this activation of JNK and p38 at the edge of the site of injury and correspondingly inhibit migration. MMCPP which inhibit the activation of downstream effectors of migration, cofilin and caldesmon, also limit the dysregulated migration. These results highlight key pathways which point to potential targets for future therapies of pulmonary hypertension with MMCPP. PMID- 27274620 TI - Holding the Inflammatory System in Check: TLRs and Their Targeted Therapy in Asthma. AB - Inflammation is a complex biological response to detrimental stimuli and can be a double-edged sword. Inflammation plays a protective role in removing pathogenic factors, but dysregulated inflammation is associated with several major fatal diseases such as asthma, cancer, and cardiovascular diseases. Asthma is a complex heterogenous disease caused by genetic and environmental factors. TLRs are the primary proteins associated with the innate and adaptive immune responses to these fatal factors and play an important role in recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which initiates the downstream immune response. Due to the complex TLRs cascade and nowadays unsuccessful control in asthma, new studies are focused on TLRs and other potential targets in TLR cascade to minimize airway inflammation. PMID- 27274623 TI - The Effect of Oxygen on Bile Resistance in Listeria monocytogenes. AB - Listeria monocytogenes is a Gram-positive facultative anaerobe that is the causative agent of the disease listeriosis. The infectious ability of this bacterium is dependent upon resistance to stressors encountered within the gastrointestinal tract, including bile. Previous studies have indicated bile salt hydrolase activity increases under anaerobic conditions, suggesting anaerobic conditions influence stress responses. Therefore, the goal of this study was to determine if reduced oxygen availability increased bile resistance of L. monocytogenes. Four strains representing three serovars were evaluated for changes in viability and proteome expression following exposure to bile in aerobic or anaerobic conditions. Viability for F2365 (serovar 4b), EGD-e (serovar 1/2a), and 10403S (serovar 1/2a) increased following exposure to 10% porcine bile under anaerobic conditions (P < 0.05). However, HCC23 (serovar 4a) exhibited no difference (P > 0.05) in bile resistance between aerobic and anaerobic conditions, indicating that oxygen availability does not influence resistance in this strain. The proteomic analysis indicated F2365 and EGD-e had an increased expression of proteins associated with cell envelope and membrane bioenergetics under anaerobic conditions, including thioredoxin-disulfide reductase and cell division proteins. Interestingly, HCC23 had an increase in several dehydrogenases following exposure to bile under aerobic conditions, suggesting that the NADH:NAD+ is altered and may impact bile resistance. Variations were observed in the expression of the cell shape proteins between strains, which corresponded to morphological differences observed by scanning electron microscopy. These data indicate that oxygen availability influences bile resistance. Further research is needed to decipher how these changes in metabolism impact pathogenicity in vivo and also the impact that this has on susceptibility of a host to listeriosis. PMID- 27274621 TI - Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations. AB - BACKGROUND: Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. AIM: In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. CONCLUSIONS: Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents. PMID- 27274624 TI - Proteomic Findings in Melanoma. AB - Although the emergence of proteomics as an independent branch of science is fairly recent, within a short period of time it has contributed substantially in various disciplines. The tool of mass spectrometry has become indispensable in the analysis of complex biological samples. Clinical applications of proteomics include detection of predictive and diagnostic markers, understanding mechanism of action of drugs as well as resistance mechanisms against them and assessment of therapeutic efficacy and toxicity of drugs in patients. Here, we have summarized the major contributions of proteomics towards the study of melanoma, which is a deadly variety of skin cancer with a high mortality rate. PMID- 27274626 TI - Treatment of Melasma with the Photoacoustic Twin Pulse Mode of Low-Fluence 1,064 nm Q-Switched Nd:YAG Laser. AB - BACKGROUND: Low-fluence 1,064 nm Q-switched Nd:YAG laser has been widely used for the treatment of melasma. Although new Q-switched Nd:YAG lasers with photoacoustic twin pulse (PTP) mode have been recently developed for high efficiency, there is limited information available for the new technique. OBJECTIVE: This study was designed to investigate the efficacy and adverse effects after few sessions of repeated low fluence 1,064 nm Q-switched Nd:YAG laser treatment with PTP mode in Asian women with melasma. METHODS: Twenty-two Korean women were treated with a total of five sessions of low-fluence PTP mode Nd:YAG laser treatment (Pastelle(r)) at 2 weeks interval. Responses to treatments were evaluated by using Melasma Area and Severity Index (MASI) scoring, colorimeter measurement, and the investigators' and patients' overall assessments. Adverse events were recorded at each visit. RESULTS: Investigators' and patients' overall assessment showed that 'significantly improved' was assessed by 13 (59.1%) and 19 of 22 patients (86.4%), respectively. MASI scores were significantly reduced by 20.4%. The lightness, measured by using a colorimeter, was significantly increased by 1.3 point. Notable adverse events were not observed. CONCLUSION: After 5 sessions of laser therapy alone, about 60% of the subjects showed significant improvement. Few sessions of repeated laser toning treatment using the PTP mode is a safe and effective way to treat facial melasma. PMID- 27274625 TI - Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal/Dermal Cross-Talk. AB - Variation in human skin and hair color is the most notable aspect of human variability and several studies in evolution, genetics and developmental biology contributed to explain the mechanisms underlying human skin pigmentation, which is responsible for differences in skin color across the world's populations. Despite skin pigmentation is primarily related to melanocytes functionality, the surrounding keratinocytes and extracellular matrix proteins and fibroblasts in the underlying dermal compartment actively contribute to cutaneous homeostasis. Many autocrine/paracrine secreted factors and cell adhesion mechanisms involving both epidermal and dermal constituents determine constitutive skin pigmentation and, whenever deregulated, the occurrence of pigmentary disorders. In particular, an increased expression of such mediators and their specific receptors frequently lead to hyperpigmentary conditions, such as in melasma and in solar lentigo, whereas a defect in their expression/release is related to hypopigmented disorders, as seen in vitiligo. All these interactions underline the relevant role of pigmentation on human evolution and biology. PMID- 27274627 TI - A Randomized, Evaluator-Blinded, Split-Face Comparison Study of the Efficacy and Safety of a Novel Mannitol Containing Monophasic Hyaluronic Acid Dermal Filler for the Treatment of Moderate to Severe Nasolabial Folds. AB - BACKGROUND: Mannitol containing monophasic filler with higher crosslinking has not been well studied for moderate and severe nasolabial fold (NLF) correction. OBJECTIVE: To compare the efficacy and safety of a novel mannitol containing hyaluronic acid (HA) filler (HA-G) with biphasic HA filler (HA-P) for moderate and severe NLF correction. METHODS: Thirteen subjects with symmetric moderate to severe NLF received HA-G (in one NLF) and HA-P (in other NLF) and were evaluated for 24 weeks. RESULTS: At both 12 and 24 weeks, the mean improvement in Genzyme 6 point grading scale from baseline was significantly greater in the side of face that was treated with HA-G than HA-P (1.96+/-0.91 vs. 1.54+/-0.73 at week 12; p=0.044, 1.88+/-0.78 vs. 1.3+/-0.79 at week 24; p=0.027, respectively). At 12 weeks, the mean Global Aesthetic Improvement Scale score was 2.92+/-0.93 for HA-G and 2.31+/-0.95 for HA-P (p=0.008). Both fillers were well tolerated. CONCLUSION: The HA filler HA-G provides better efficacy and similar local tolerability compared with HA-P in 6 months following treatment for moderate and severe NLF. PMID- 27274628 TI - Protective Effect of Topical Vitamin D3 against Photocarcinogenesis in a Murine Model. AB - BACKGROUND: Although the incidence of non-melanoma skin cancer is increasing, there are no effective practical preventive measures other than avoiding sun exposure. OBJECTIVE: To elucidate the protective effect of topical application of biologically active vitamin D3 (calcitriol) on skin cancer development caused by exposure to ultraviolet (UV). METHODS: Groups of hairless mice were topically treated with either calcitriol or vehicle immediately after exposure to UVB and UVA three times weekly for the initial 20 weeks, and without UV exposure in the following 6 weeks. Tumor number was counted and biopsies were done for histopathologic analysis. The changes of cyclobutane pyrimidine dimer (CPD) were evaluated 1 hour and 11 hours after short term of UV exposure and application of calcitriol. For safety evaluation, blood test and body weights were evaluated at 23rd and 25th week. RESULTS: Total tumor count and number of tumors less than 3 mm in size tended to be fewer in calcitriol group, and tumors more than 3 mm in size showed significantly lower tumor formation rate in calcitriol group. Single application of calcitriol reduced CPD at 1 hour and 11 hours after UV exposure. Histopathologic analysis showed tumors with lower grade malignancy in calcitriol group which suggested a delay in tumor progression. However, serum levels of calcium and phosphate in calcitriol group were above normal range, and weight loss was found. CONCLUSION: Topical calcitriol may suppress the formation and progression of UV-induced non-melanoma skin cancer by enhancing the repair mechanism of UV damage. PMID- 27274629 TI - Analysis of Dermatologic Diseases in Neurosurgical In-Patients: A Retrospective Study of 463 Cases. AB - BACKGROUND: Both the skin and the neurologic system are derived from the ectoderm during embryogenesis, and thus patients with neurologic disorders may have accompanying dermatologic diseases. For example, seborrheic dermatitis is more frequently observed in patients with Parkinsonism and other neurologic disorders. To date, however, there has been limited review on dermatologic diseases in neurosurgical in-patients. OBJECTIVE: The purpose of this study was to characterize dermatological problems encountered in a neurosurgery unit and to compare these data to previous reports of in-patient dermatologic consultations. METHODS: A retrospective review was conducted over all in-patient dermatology consultations from the neurosurgery unit during a 3-year period. RESULTS: Of 2,770 dermatology consultations, 463 (16.7%) came from the department of neurosurgery. The most frequent age group was the 6th decade of life, and the ratio of men to women was 1.07. Consults were most frequently placed from patients with intracranial hemorrhage (23.8%). Eczema/dermatitis (36.5%; n=204) and cutaneous infections (27.0%; n=151) accounted for more than half of all dermatological consultations, followed by cutaneous adverse drug reactions (11.8%; n=66). Additionally, seborrheic dermatitis was significantly more frequent (p=0.048, odds ratio=1.96) in patients with intracranial hemorrhage. CONCLUSION: This study characterizes the distribution of skin disorders in patients admitted to the neurosurgery service based on the consultations that have been made for dermatologic evaluation. Collaboration between the neurosurgeons and dermatologists may improve the quality of patient care and help to better predict the occurrence of these conditions. PMID- 27274630 TI - Correlation between Severity of Atopic Dermatitis and Sleep Quality in Children and Adults. AB - BACKGROUND: The atopic dermatitis (AD) can limit a patient's physical and psychosocial development as well as lower their overall quality of life (QOL), including sleep quality. OBJECTIVE: The purpose of this study was to evaluate the relationships between clinical disease severity, QOL and sleep quality in children and adults with AD. METHODS: The SCORing atopic dermatitis (SCORAD) was examined to evaluate the severity of AD in fifty adult AD patients and 50 children AD patients. A questionnaire based on the children's sleep habits questionnaire (CSHQ) and the children's dermatology life quality index (CDLQI) were used to evaluate QOL and sleep disturbance in children AD patients. The Pittsburgh sleep quality index (PSQI) and dermatology life quality index (DLQI) were used in adult AD patients. RESULTS: The SCORAD and CSHQ score, the SCORAD and CDLQI score and the CSHQ and CDLQI score demonstrated significant correlations. The SCORAD and PSQI score showed no significant correlation. However, there were significant correlations between the SCORAD and DLQI score and the PSQI and DLQI score. CONCLUSION: Increasing severity of AD affects sleep quality in child AD patients. In adults, even though the total score of the sleep questionnaire is not associated with the severity of AD, two components of sleep questionnaire are associated with the severity of AD. There is a significant correlation between sleep quality and QOL in both children and adults. Therefore, we suggest that evaluating the sleep quality as well as clinical severity of the disease is necessary in the management of AD patients. PMID- 27274631 TI - Epigallocatechin Gallate-Mediated Alteration of the MicroRNA Expression Profile in 5alpha-Dihydrotestosterone-Treated Human Dermal Papilla Cells. AB - BACKGROUND: Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level. OBJECTIVE: We showed that epigallocatechin gallate (EGCG), a major component of green tea, protects DHT induced cell death by regulating the cellular miRNA expression profile. METHODS: We used a miRNA microarray to identify miRNA expression levels in human dermal papilla cells (DPCs). We investigated whether the miRNA expression influenced the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular ROS levels, and senescence. RESULTS: EGCG protected against the effects of DHT by altering the miRNA expression profile in human DPCs. In addition, EGCG attenuated DHT-mediated cell death and growth arrest and decreased intracellular ROS levels and senescence. A bioinformatics analysis elucidated the relationship between the altered miRNA expression and EGCG-mediated protective effects against DHT. CONCLUSION: Overall, our results suggest that EGCG ameliorates the negative effects of DHT by altering the miRNA expression profile in human DPCs. PMID- 27274632 TI - Clinical Features and Awareness of Hand Eczema in Korea. AB - BACKGROUND: Hand eczema is one of the most common skin disorders and negatively affects quality of life. However, a large-scale multicenter study investigating the clinical features of patients with hand eczema has not yet been conducted in Korea. OBJECTIVE: To identify the prevalence of various hand diseases, which is defined as all cutaneous disease occurring in hands, and to investigate the clinical features of patients with hand eczema and the awareness about hand eczema in the general population and to compare the prevalence of hand eczema between health care providers and non-health care providers. METHODS: To estimate the prevalence of hand diseases, we analyzed the medical records of patients from 24 medical centers. Patients were assessed by online and offline questionnaires. A 1,000 from general population and 913 hand eczema patients answered the questionnaire, for a total of 1,913 subjects. RESULTS: The most common hand disease was irritant contact dermatitis. In an online survey, the lifetime prevalence of hand eczema was 31.2%. Hand eczema was more likely to occur in females (66.0%) and younger (20~39 years, 53.9%). Health care providers and housewives were the occupations most frequently associated with hand eczema. Winter (33.6%) was the most common season which people experienced aggravation. The 63.0% and 67.0% answered that hand eczema hinders their personal relationship and negatively affects daily living activities, respectively. CONCLUSION: Hand eczema is a very common disease and hinders the quality of life. The appropriate identification of hand eczema is necessary to implement effective and efficient treatment. PMID- 27274633 TI - CSP0510 Lotion as a Novel Moisturizer Containing Citric Acid and Trisodium Phosphate Relieves Objective and Subjective Symptoms of Atopic Dermatitis. AB - BACKGROUND: Moisturizers with anti-inflammatory or anti-itch activity should be developed for the safe and effective management of atopic dermatitis (AD). OBJECTIVE: This study evaluated the efficacy of a newly developed moisturizer, CSP0510 lotion (Twolines Inc., Korea), containing citric acid (CA) and trisodium phosphate (TSP) as active ingredients, in mild to moderate AD. METHODS AND RESULTS: CSP0510 lotion applied twice daily for 4 weeks to eczematous lesions improved objective and subjective (itch) symptoms of AD. The physician's global assessment (PGA) score for objective symptoms decreased from 2.5+/-0.6 before application to 1.3+/-0.5 after application in the CSP0510-treated group (n=42, p<0.001). Also, the PGA score decreased from 2.3+/-0.6 to 1.9+/-0.5 by vehicle treated (without CA and TSP) control group (p=0.001), but there was no statistical difference between CSP0510-treated and vehicle-treated groups (p=0.089). The visual analogue scale score for itch decreased from 4.8+/-1.3 to 2.0+/-0.9 in the CSP0510-treated group (p<0.001), and from 4.6+/-1.1 to 3.5+/-0.9 in the control group (p=0.075), showing a statistical significance between two groups (p=0.002). Our results in humans were further supported by in vitro and animal experiments. In HaCaT cells treated with compound 48/80 (7.5 ug/ml), CA:TSP (1:1, vol:vol) synergistically suppressed the compound 48/80-induced upregulation of thymic stromal lymphopoietin, nerve grow factor, and calcitonin gene-related peptide. Application of CSP0510 to the dorsal skin of hairless mice for 3 weeks suppressed the oxazolone-induced allergic skin inflammation. CONCLUSION: In conclusion, CSP0510 lotion has anti-itch and anti-inflammatory activity in the skin, which improves both objective and subjective symptoms of AD. PMID- 27274635 TI - The Association between Psoriasis Area and Severity Index and Cardiovascular Risk Factor in Korean Psoriasis Patients. AB - BACKGROUND: Psoriasis is associated with increased risk of cardiovascular morbidities, especially in severe cases. Severity of the disease has been known to be associated with higher prevalence of these risk factors. However, in the absence of robust measurements, studies to date relied mostly on treatment spectrum as a proxy for the severity. OBJECTIVE: To evaluate the relationship between psoriasis area and severity index (PASI) and cardiovascular risk factors in Korean patients. METHODS: Presence of diabetes mellitus (DM), hypertension, smoking history was surveyed through questionnaires and serum lipid profile analysis were done after fasting overnight. The severity of psoriasis was assessed using PASI scores: mild, <10; moderate to severe, >=10. Cardiovascular risk factors such as smoking, hypertension, diabetes and dyslipidemia were compared between the mild group and moderate to severe group. The prevalence of diabetes and hypertension was compared among these two groups of psoriasis patients and the general population based control; age and gender were matched among three groups accordingly prior to analysis. RESULTS: A total of 256 patients with plaque type psoriasis were included. Between mild group and moderate to severe group, significant differences of cardiovascular risk factors including lipid profile were not discovered except in triglyceride level. Comparing to general population, prevalence of diabetes was found significantly higher in psoriasis patients while that of hypertension was similar. CONCLUSION: Our results suggest that among cardiovascular risks, presence of DM and triglyceride level seem to be associated with the presence of psoriasis in Korean psoriasis patients, while other factors may not contribute meaningfully. PMID- 27274634 TI - Ampelopsis japonica Makino Extract Inhibits the Inflammatory Reaction Induced by Pathogen-Associated Molecular Patterns in Epidermal Keratinocytes. AB - BACKGROUND: Keratinocytes are the major cells in epidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been known that pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. OBJECTIVE: The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs induced inflammatory reaction of keratinocytes. METHODS: The effects of AE were determined using poly (I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. RESULTS: In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated nuclear factor-kappaB signaling pathway. In imiquimod-induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. CONCLUSION: These results suggest that AE may be a potential candidate for the treatment of skin inflammation. PMID- 27274636 TI - Efficacy and Safety of Alitretinoin for Chronic Hand Eczema in Korean Patients. AB - BACKGROUND: Chronic hand eczema (CHE) tends to be refractory to conventional therapy. Previous clinical trials have found that a 24-week treatment course of oral alitretinoin is effective and well tolerated for CHE treatment. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of oral alitretinoin in Korean CHE patients. METHODS: A total of 27 patients with moderate to severe CHE took 30 mg of alitretinoin daily for 12 weeks. The primary efficacy parameter was the physician's global assessment (PGA). The response was defined as a patient being "clear" or "almost clear" of disease. The secondary efficacy parameters were the modified total lesion symptom score (mTLSS) and the patients' global assessment (PaGA). All adverse events and laboratory abnormalities were recorded during the treatment period. RESULTS: Alitretinoin led to CHE symptom improvement in 44.4% of patients. The PGA, mTLSS, and PaGA scores correlated well with each other. Reported adverse events were typical retinoid class effects and headache was the most common. CONCLUSION: Taking 30 mg of oral alitretinoin daily for 12 weeks was found to be effective in treating Korean patients with CHE, compared with the 24 week-treatment shown in previous studies. PMID- 27274637 TI - CD30-Positive Anaplastic Lymphoma Kinase-Negative Systemic Anaplastic Large-Cell Lymphoma in a 9-Year-Old Boy. AB - Anaplastic large-cell lymphoma (ALCL) is a CD30-positive T-cell/null-cell lymphoma that is clinically classified into either primary cutaneous ALCL or systemic ALCL (S-ALCL) sub-types. Because 90% of childhood S-ALCL cases are anaplastic lymphoma kinase (ALK)-positive, there is a lack of data on ALK negative S-ALCL cases among pediatric patients. Herein, we report a rare case of ALK-negative S-ALCL in a 9-year-old Korean boy who initially presented with itchy erythematous maculopapules and an erosive nodule on the trunk area. We emphasize the need of high index of suspicion of an underlying malignant disease in the presence of refractory eczematous lesions. PMID- 27274638 TI - Tumoral Calcinosis as an Initial Complaint of Juvenile-Onset Amyopathic Dermatomyositis. AB - Calcinosis is rarely observed in juvenile-onset amyopathic dermatomyositis in contrast to juvenile-onset dermatomyositis. A 6-year-old female presented with several 0.5 to 2 cm-sized painless grouped masses on both knees for 3 years. The patient also presented with multiple erythematous scaly patches and plaques on both elbows, knuckles, buttock, ankles and cheeks. Her mother had similar skin lesions which were erythematous scaly patches on the knuckles and elbows, since her childhood. When skin biopsy was performed from a left knee nodule, liquid chalky discharge was observed. The biopsy results were consistent with calcinosis cutis. Other biopsies from erythematous patch of the patient and erythematous patch of her mother showed vacuolization of basal cell layer with inflammatory cell infiltrations. Laboratory findings showed normal range of serum phosphorus (4.5 mg/dl), calcium (9.3 mg/dl), 1,25-dihydroxy-vitamin D (10.8 ng/ml) and parathyroid hormone levels (11 pg/ml). Both patient and her mother had no history of muscle weakness and showed normal levels of muscle-specific enzyme. Both patients were diagnosed with juvenile-onset amyopathic dermatomyositis based on histopathology and cutaneous manifestations with no evidence of muscle weakness and no serum muscle enzyme abnormalities. Tumoral calcium deposits observed in daughter was diagnosed as dystrophic calcinosis which can be rarely seen in juvenile-onset amyopathic dermatomyositis. The patient is being treated with oral acetazolamide (40 mg/kg/d) for calcinosis. PMID- 27274639 TI - Efficacy of Omalizumab in a Patient with Angioedema Clinically Resembling a Hereditary Angioedema. PMID- 27274640 TI - A Case of Papular Mycosis Fungoides: A New Clinical Variant of Early Mycosis Fungoides. PMID- 27274641 TI - A Case of Phaeohyphomycosis Caused by Exophiala lecanii-corni. PMID- 27274642 TI - Classic Juvenile Pityriasis Rubra Pilaris Treated with Oral Alitretinoin. PMID- 27274643 TI - Histiocytic Infiltrate in Angioimmunoblastic T-Cell Lymphoma with Cutaneous Nodules and Progressive Ulceration: A Rare Manifestation. PMID- 27274644 TI - Cutaneous Metastatic Rectal Adenocarcinoma in Zosteriform Distribution. PMID- 27274645 TI - Interstitial Granulomatous Dermatitis Associated with Rheumatoid Arthritis. PMID- 27274646 TI - A Case of Multiple Canaliform Median Raphe Cysts Showing a Mixed Type Lining of Epithelium: A Case Report and Review of the Literature. PMID- 27274647 TI - Blue Toe Syndrome as an Early Sign of Disseminated Intravascular Coagulation. PMID- 27274648 TI - Development of Rheumatoid Nodules after Anti-Tumor Necrosis Factor-alpha Treatment with Adalimumab for Rheumatoid Arthritis. PMID- 27274649 TI - Acquired Unilateral Nevoid Telangiectasia Accompanied by Liver Metastasis of Colon Cancer. PMID- 27274650 TI - The Efficacy and Prognostic Factors for Long Pulse Neodymium: Yttrium-Aluminum Garnet Laser Treatment on Onychomycosis: A Pilot Study. PMID- 27274652 TI - A Case of Multiple Desmoplastic Trichoepithelioma. PMID- 27274651 TI - Exacerbation of Psoriasis after Imatinib Mesylate Treatment. PMID- 27274653 TI - A Case of Terra Firma-Forme Dermatosis: Differentiation from Other Dirty Appearing Diseases. PMID- 27274654 TI - Using Multilevel Regression Mixture Models to Identify Level-1 Heterogeneity in Level-2 Effects. AB - This paper proposes a novel exploratory approach for assessing how the effects of level-2 predictors differ across level-1 units. Multilevel regression mixture models are used to identify latent classes at level-1 that differ in the effect of one or more level-2 predictors. Monte Carlo simulations are used to demonstrate the approach with different sample sizes and to demonstrate the consequences of constraining 1 of the random effects to zero. An application of the method to evaluate heterogeneity in the effects of classroom practices on students is used to show the types of research questions which can be answered with this method and the issues faced when estimating multilevel regression mixtures. PMID- 27274655 TI - A Method for Retrieval of Adverse Event Terms in Clinical Trial Databases Using Standardised MedDRA Queries. AB - BACKGROUND: Standardized MedDRA Queries (SMQs) are sets of terms determined by experts that are used to identify adverse events (AEs) related to different disease processes. Their use can be challenging because most SMQs have 50 to 100 preferred terms and AE databases can have many thousands of events. AIM: The aim of this study is to develop a technique where AEs corresponding to preferred terms in SMQs may be easily detected. METHODOLOGY: The method I developed uses the Table Join function of the JMP(r) software program to quickly and easily probe clinical trial AE databases. The SMQ Severe cutaneous adverse reactions was used as a probe in a mock AE dataset. Potentially confounding demographic or study-specific factors were evaluated by combining these datasets with the dataset containing the AEs identified with the SMQs. RESULTS: AEs were successfully detected in an AE database using the method described. Cases with potential confounding factors, such as concomitant medications, were identified. CONCLUSIONS: The method developed allows for AEs to be found in clinical trial databases and evaluated using software programs that are readily available to clinical researchers. PMID- 27274656 TI - Cardiorespiratory Effects of One-Legged High-Intensity Interval Training in Normoxia and Hypoxia: A Pilot Study. AB - A higher-than-average maximal oxygen consumption (VO2max), is closely associated with decreased morbidity and mortality and improved quality of life and acts as a marker of cardiorespiratory fitness. Although there is no consensus about an optimal training method to enhance VO2max, nevertheless training of small muscle groups and repeated exposure to hypoxia seem to be promising approaches. Therefore, this study was aimed at gaining innovative insights into the effects of small muscle group training in normoxia and hypoxia. Thirteen healthy participants were randomly assigned to the hypoxic (HG, n = 7) or normoxic (NG, n = 6) training group. Both groups completed nine high-intensity interval training sessions in 3 wks. The NG performed the training in normoxia (FiO2: 0.21; ~ 600 m) and the HG in hypoxia (FiO2: 0.126; ~ 4500 m). Each session consisted of 4 x 4 min one-legged cycling at 90% of maximal heart rate separated by 4 min recovery periods. Before and after the intervention period, VO2max and peak power output (Wmax) and responses to submaximal cycling (100 and 150 watts) were assessed in a laboratory cycling test. Peak power output significantly improved within both groups (9.6 +/- 4.8% and 12.6 +/- 8.9% for HG and NG, respectively) with no significant interaction (p = 0.277). However, VO2max only significantly increased after training in hypoxia from 45.4 +/- 10.1 to 50.0 +/- 9.8 ml/min/kg (10.8 +/- 6.0%; p = 0.002) with no significant interaction (p = 0.146). The maximal O2 pulse improved within the HG and demonstrated a significant interaction (p = 0.040). One-legged cycling training significantly improved VO2max and peak power output. Training under hypoxic conditions may generate greater effects on VO2max than a similar training in normoxia and is considered as a promising training method for improving cardiorespiratory fitness. Key pointsNine sessions of one legged high-intensity interval training significantly improved physical fitness.One-legged hypoxic training significantly improved Wmax, VO2max and submaximal performance.One-legged training in normoxia only improved Wmax but did not significantly improve VO2max and submaximal performance. PMID- 27274657 TI - Neural Markers of Performance States in an Olympic Athlete: An EEG Case Study in Air-Pistol Shooting. AB - This study focused on identifying the neural markers underlying optimal and suboptimal performance experiences of an elite air-pistol shooter, based on the tenets of the multi-action plan (MAP) model. According to the MAP model's assumptions, skilled athletes' cortical patterns are expected to differ among optimal/automatic (Type 1), optimal/controlled (Type 2), suboptimal/controlled (Type 3), and suboptimal/automatic (Type 4) performance experiences. We collected performance (target pistol shots), cognitive-affective (perceived control, accuracy, and hedonic tone), and cortical activity data (32-channel EEG) of an elite shooter. Idiosyncratic descriptive analyses revealed differences in perceived accuracy in regard to optimal and suboptimal performance states. Event Related Desynchronization/Synchronization analysis supported the notion that optimal-automatic performance experiences (Type 1) were characterized by a global synchronization of cortical arousal associated with the shooting task, whereas suboptimal controlled states (Type 3) were underpinned by high cortical activity levels in the attentional brain network. Results are addressed in light of the neural efficiency hypothesis and reinvestment theory. Perceptual training recommendations aimed at restoring optimal performance levels are discussed. Key pointsWe investigated the neural markers underlying optimal and suboptimal performance experiences of an elite air-pistol shooter.Optimal/automatic performance is characterized by a global synchronization of cortical activity associated with the shooting task.Suboptimal controlled performance is characterized by high cortical arousal levels in the attentional brain networks.Focused Event Related Desynchronization activity during Type 1 performance in frontal midline theta was found, with a clear distribution of Event Related Synchronization in the frontal and central areas just prior to shot release.Event Related Desynchronization patterns in low Alpha band for Type 3 performance suggest that higher levels of general cortical arousal are associated with suboptimal-controlled performance states. PMID- 27274658 TI - Effects of a Non-Circular Chainring on Sprint Performance During a Cycle Ergometer Test. AB - Non-circular chainrings have been reported to alter the crank angular velocity profile over a pedal revolution so that more time is spent in the effective power phase. The purpose of this study was to determine whether sprint cycling performance could be improved using a non-circular chainring (Osymetric: ellipticity 1.25 and crank lever mounted nearly perpendicular to the major axis), in comparison with a circular chainring. Twenty sprint cyclists performed an 8 s sprint on a cycle ergometer against a 0.5 N/kg(-1) friction force in four crossing conditions (non-circular or circular chainring with or without clipless pedal). Instantaneous force, velocity and power were continuously measured during each sprint. Three main characteristic pedal downstrokes were selected: maximal force (in the beginning of the sprint), maximal power (towards the middle), and maximal velocity (at the end of the sprint). Both average and instantaneous force, velocity and power were calculated during the three selected pedal downstrokes. The important finding of this study was that the maximal power output was significantly higher (+ 4.3%, p < 0.05) when using the non-circular chainring independent from the shoe-pedal linkage condition. This improvement is mainly explained by a significantly higher instantaneous external force that occurs during the downstroke. Non-circular chainring can have potential benefits on sprint cycling performance. Key pointsThe Osymetric non-circular chainring significantly maximized crank power by 4.3% during sprint cycling, in comparison with a circular chainring.This maximal power output improvement was due to significant higher force developed when the crank was in the effective power phase.This maximal power output improvement was independent from the shoe-pedal linkage condition.Present benefits provided by the non-circular chainring on pedalling kinetics occurred only at high cadences. PMID- 27274659 TI - Determining Dimensionality of Exercise Readiness Using Exploratory Factor Analysis. AB - Assessment of "exercise readiness" is a central component to the flexible non linear periodization (FNLP) method of organizing training workloads, but the underlying factor structure of this construct has not been empirically determined. The purpose of this study was to assess construct dimensionality of exercise readiness using exploratory factor analysis. The result of which serve as initial steps of developing a brief measure of exercise readiness. Participants consisted of students recruited from undergraduate Kinesiology courses at a racially diverse, southern University. Independent, anonymous online survey data were collected across three stages: 1) generation of item pool (n = 290), 2) assessment of face validity and refinement of item pool (n = 168), and 3) exploratory factor analysis (n = 684). A principal axis factor analysis was conducted with 41 items using oblique rotation (promax). Four statistically significant factors, as determined through parallel analysis, explained 61.5% of the variance in exercise readiness. Factor 1 contained items that represented vitality (e.g., lively, revived). Factor 2 items related to physical fatigue (e.g. tired, drained). Factors 3 and 4 were descriptive of, discomfort (e.g. pain, sick) and health (i.e. healthy, fit), respectively. This inductive approach indicates that exercise readiness is comprised of four dimensions: vitality, physical fatigue, discomfort, and health. This finding supports readiness assessment techniques currently recommended for practitioners according to the FNLP model. These results serve as a theoretical foundation upon which to further develop and refine a brief survey instrument to measure exercise readiness. Key pointsAssessment of exercise readiness is a key component in implementing an exercise program based on flexible nonlinear periodization, but the dimensionality of this concept has not been empirically determined.Based on a series of surveys and a robust exploratory factor analysis, exercise readiness appears to be supported by 4 dimensions: vitality, physical fatigue, discomfort, and health.These findings prove a theoretical basis to construct a brief, multidimensional measure of exercise readiness. PMID- 27274660 TI - Comparison of Level and Graded Treadmill Tests to Evaluate Endurance Mountain Runners. AB - Mountain endurance running has increased in popularity in recent years. Thus the aim of the present study was to determine if maximal oxygen uptake (VO2max) and energy cost of running (Cr) measured during level and uphill running are associated. Ten high level male endurance mountain runners performed three maximal oxygen uptake tests at three slope conditions (0, 12.5 and 25%). Metabolic data, step frequency (SF) and step length (SL) were recorded. No significant differences were found in VO2max (63.29 (+/-3.84), 63.97 (+/-3.54) and 63.70 (+/-3.58) mlO2/kg(-1)/min(-1)) or associated metabolic data at 0, 12.5 and 25% slope respectively. High intra-individual correlations were found between metabolic data measured in the three conditions. The energy cost of running was significantly different between slopes (0.192 (+/-0.01), 0.350 (+/-0.029) and 0.516 (+/-0.035) mlO2/kg(-1)/min(-1), p < 0.01), 0, 12.5 and 25% respectively. However, Cr0% was not correlated with either Cr25% or Cr12.5% (rs = 0.09 and rs = 0.10), in contrast, Cr25% and Cr12.5% were correlated (rs = 0.78). Step length was positively correlated with speed under the three slope conditions. Step frequency was significantly lower at 25 compared to 12.5 and 0% slope. We found that the maximum aerobic power did not differ between level and graded treadmill tests. However, the increase in Cr on the inclined versus level conditions varied between subjects. None of the measured anthropometric or kinematic variables could explain the higher increase in Cr of some subjects when running uphill. Thus, a short graded (5min at 12.5%) running test should be performed at a submaximal velocity (around 40% of level vVO2max) to enhance understanding of an endurance runner's uphill capability. Key pointsIn elite endurance mountain runners, there is no difference in VO2max values between level and uphill running.In a homogeneous group of mountain runners, uphill Cr is not associated with level Cr.To assess performance potential of endurance mountain runners, a standardized uphill running protocol should be performed. PMID- 27274661 TI - The Effects of a Duathlon Simulation on Ventilatory Threshold and Running Economy. AB - Multisport events continue to grow in popularity among recreational, amateur, and professional athletes around the world. This study aimed to determine the compounding effects of the initial run and cycling legs of an International Triathlon Union (ITU) Duathlon simulation on maximal oxygen uptake (VO2max), ventilatory threshold (VT) and running economy (RE) within a thermoneutral, laboratory controlled setting. Seven highly trained multisport athletes completed three trials; Trial-1 consisted of a speed only VO2max treadmill protocol (SOVO2max) to determine VO2max, VT, and RE during a single-bout run; Trial-2 consisted of a 10 km run at 98% of VT followed by an incremental VO2max test on the cycle ergometer; Trial-3 consisted of a 10 km run and 30 km cycling bout at 98% of VT followed by a speed only treadmill test to determine the compounding effects of the initial legs of a duathlon on VO2max, VT, and RE. A repeated measures ANOVA was performed to determine differences between variables across trials. No difference in VO2max, VT (%VO2max), maximal HR, or maximal RPE was observed across trials. Oxygen consumption at VT was significantly lower during Trial-3 compared to Trial-1 (p = 0.01). This decrease was coupled with a significant reduction in running speed at VT (p = 0.015). A significant interaction between trial and running speed indicate that RE was significantly altered during Trial-3 compared to Trial-1 (p < 0.001). The first two legs of a laboratory based duathlon simulation negatively impact VT and RE. Our findings may provide a useful method to evaluate multisport athletes since a single-bout incremental treadmill test fails to reveal important alterations in physiological thresholds. Key pointsDecrease in relative oxygen uptake at VT (ml.kg(-1).min( 1)) during the final leg of a duathlon simulation, compared to a single-bout maximal run.We observed a decrease in running speed at VT during the final leg of a duathlon simulation; resulting in an increase of more than 2 minutes to complete a 5 km run.During our study, highly trained athletes were unable to complete the final 5 km run at the same intensity that they completed the initial 10 km run (in a laboratory setting).A better understanding, and determination, of training loads during multisport training may help to better periodize training programs; additional research is required. PMID- 27274662 TI - Plantar Pressures During Long Distance Running: An Investigation of 10 Marathon Runners. AB - The objective of this study was to record plantar pressures using an in-shoe measuring system before, during, and after a marathon run in ten experienced long distance runners with a mean age of 37.7 +/- 11.5 years. Peak and mean plantar pressures were recorded before, after, and every three km during a marathon race. There were no significant changes over time in peak and mean plantar pressures for either the dominant or non-dominant foot. There were significant between foot peak and mean plantar pressure differences for the total foot (p = 0.0001), forefoot (p = 0.0001), midfoot (p = 0.02 resp. p = 0.006), hindfoot (p = 0.0001), first ray (p = 0.01 resp. p = 0.0001) and MTP (p = 0.05 resp. p = 0.0001). Long distance runners do not demonstrate significant changes in mean or peak plantar foot pressures over the distance of a marathon race. However, athletes consistently favoured their dominant extremity, applying significantly higher plantar pressures through their dominant foot over the entire marathon distance. Key pointsFatigue does not increase foot pressuresEvery runner has a dominant foot where pressures are higher and that he/she favoursFoot pressures do not increase over the distance of a marathon run. PMID- 27274663 TI - Accuracy and Reliability of a New Tennis Ball Machine. AB - The aim was to evaluate the reliability of a newly-developed ball machine named 'Hightof', on the field and to assess its accuracy. The experiment was conducted in the collaboration of the 'Hawk-Eye' technology. The accuracy and reliability of this ball machine were assessed during an incremental test, with 1 min of exercise and 30 sec of recovery, where the frequency of the balls increased from 10 to 30 balls.min(-1). The initial frequency was 10 and increased by 2 until 22, then by 1 until 30 balls.min(-1). The reference points for the impact were 8.39m from the net and 2.70m from lateral line for the right side and 2.83m for the left side. The precision of the machine was similar on the right and left sides (0.63 +/- 0.39 vs 0.63 +/- 0.34 m). The distances to the reference point were 0.52 +/- 0.42, 0.26 +/- 0.19, 0.52 +/- 0.37, 0.28 +/- 0.19 m for the Y-right, X right, Y-left and X-left impacts. The precision was constant and did not increase with the intensity. (e.g ball frequency). The ball velocity was 86.3 +/- 1.5 and 86.5 +/- 1.3 km.h(-1) for the right and the left side, respectively. The coefficient of variation for the velocity ranged between 1 and 2% in all stages (ball velocity ranging from 10 to 30 balls.min(-1)). CONCLUSION: both the accuracy and the reliability of this new ball machine appear satisfying enough for field testing and training. Key pointsThe reliability and accuracy of a new ball machine named 'Hightof' were assessed.The impact point was reproducible and similar on the right and left sides (+/-0.63 m).The precision was constant and did not increase with the intensity (e.g ball frequency).The coefficient of variation of the ball velocity ranged between 1 and 2% in all stages (ball velocity ranging from 10 to 30 balls.min(-1)). PMID- 27274664 TI - Differing Roles of Functional Movement Variability as Experience Increases in Gymnastics. AB - Current theories, like Ecological Dynamics, propose that inter-trial movement variability is functional when acquiring or refining movement coordination. Here, we examined how age-based experience levels of gymnasts constrained differences in emergent movement pattern variability during task performance. Specifically, we investigated different roles of movement pattern variability when gymnasts in different age groups performed longswings on a high bar, capturing the range of experience from beginner to advanced status. We also investigated the functionality of the relationships between levels of inter-trial variability and longswing amplitude during performance. One-hundred and thirteen male gymnasts in five age groups were observed performing longswings (with three different experience levels: beginners, intermediates and advanced performers). Performance was evaluated by analysis of key events in coordination of longswing focused on the arm-trunk and trunk-thigh segmental relations. Results revealed that 10 of 18 inter-trial variability measures changed significantly as a function of increasing task experience. Four of ten variability measures conformed to a U shaped function with age implying exploratory strategies amongst beginners and functional adaptive variability amongst advanced performers. Inter-trial variability of arm-trunk coordination variables (6 of 10) conformed to a ?-shaped curve, as values were reduced to complete the longswings. Changes in coordination variability from beginner to intermediate status were largely restrictive, with only one variability measure related to exploration. Data revealed how inter trial movement variability in gymnastics, relative to performance outcomes, needs careful interpretation, implying different roles as task experience changes. Key pointsInter-trial variability while performing longswings on a high bar was assessed in a large sample (113 participants) divided into five age groups (form beginners to advanced gymnasts). Longswing assessment allowed us to evaluate inter-trial variability in representative performance context.Coordination variability presented two different configurations across experience levels depending on the variable of interest: either a U-shaped or a L- or ?-shaped graph.Increased inter-trial variability of the functional phase events offered flexibility to adapt the longswing performance in the advanced gymnasts, while decreasing variability in arm-trunk coordination modes was critical to improve longswing and to achieve the most advanced level.In addition, the relationship between variability measures and the global performance outcome (i.e. the swing amplitude) revealed different functional roles of movement variability (exploratory or restrictive) as a function of changes in experience levels. PMID- 27274665 TI - Alterations of Vertical Jump Mechanics after a Half-Marathon Mountain Running Race. AB - The fatiguing effect of long-distance running has been examined in the context of a variety of parameters. However, there is scarcity of data regarding its effect on the vertical jump mechanics. The purpose of this study was to investigate the alterations of countermovement jump (CMJ) mechanics after a half-marathon mountain race. Twenty-seven runners performed CMJs before the race (Pre), immediately after the race (Post 1) and five minutes after Post 1 (Post 2). Instantaneous and ensemble-average analysis focused on jump height and, the maximum peaks and time-to-maximum peaks of: Displacement, vertical force (Fz), anterior-posterior force (Fx), Velocity and Power, in the eccentric (tECC) and concentric (tCON) phase of the jump, respectively. Repeated measures ANOVAs were used for statistical analysis (p <= 0.05). The jump height decrease was significant in Post 2 (-7.9%) but not in Post 1 (-4.1%). Fx and Velocity decreased significantly in both Post 1 (only in tECC) and Post 2 (both tECC and tCON). Alpha timing shift of the Fz peaks (earlier during tECC and later during tCON) and altered relative peak times (only in tECC) were also observed. Ensemble average analysis revealed several time intervals of significant post-race alterations and a timing shift in the Fz-Velocity loop. An overall trend of lowered post-race jump output and mechanics was characterised by altered jump timing, restricted anterior-posterior movement and altered force-velocity relations. The specificity of mountain running fatigue to eccentric muscle work, appears to be reflected in the different time order of the post-race reductions, with the eccentric phase reductions preceding those of the concentric one. Thus, those who engage in mountain running should particularly consider downhill training to optimise eccentric muscular action. Key pointsThe 4.1% reduction of jump height immediately after the race is not statistically significantThe eccentric phase alterations of jump mechanics precede those of the concentric ones.Force-velocity alterations present a timing shift rather than a change in force or velocity magnitude. PMID- 27274667 TI - Does Body Mass Index Influence Behavioral Regulations, Dispositional Flow and Social Physique Anxiety in Exercise Setting? AB - The purpose of this study was to examine differences in behavioral regulations, dispositional flow, social physique anxiety of exercisers in terms of body mass index (BMI). 782 university students participated in this study. Dispositional Flow State Scale-2, Behavioral Regulations in Exercise Questionnaire-2, Social Physique Anxiety Scale and Physical Activity Stages of Change Questionnaire were administered to participants. After controlling for gender, analysis indicated significant differences in behavioral regulations, dispositional flow and social physique anxiety of exercise participants with regards to BMI. In summary, the findings demonstrate that normal weighted participants exercise for internal reasons while underweighted participants are amotivated for exercise participation. Additionally, participants who are underweight had higher dispositional flow and lower social physique anxiety scores than other BMI classification. Key pointsNormal weighted participants exercise for internal reasons.Underweighted participants are amotivated for exercise participation.Underweighted participants had higher dispositional flow.Underweighted participants have lower social physique anxiety scores than normal weighted, overweight and obese participants. PMID- 27274666 TI - The Association Analysis between ACE and ACTN3 Genes Polymorphisms and Endurance Capacity in Young Cross-Country Skiers: Longitudinal Study. AB - Endurance performance depends on the integration of several phenotypic traits influenced by multiple environmental and genetic factors. Objectives of the study were: (1) to examine the genotypic frequencies of the ACE I/D, ACTN3 R577X polymorphisms and endurance performance-related phenotypes, (2) to evaluate the dynamics of endurance performance parameters during a 5-year period in relation to ACE I/D and ACTN3 R577X genotypes in Estonian young skiers. Determination of VO2peak was performed in 58 skiers aged 15-19 years (41 males, 17 females) during a 5-year period. The control group consisted of 322 healthy non-athletic subjects (145 males, 177 females). The study groups were genotyped for the ACE I/D and ACTN3 R577X variants. Frequencies of the ACE ID and ACTN3 RR genotypes were significantly higher (p = 0.047 and p = 0.003, respectively) and the RX genotype was lower (p = 0.008) in young male skiers compared with controls. A significant relationship was found between change (Delta) of training volume and DeltaVO2peak (mL.kg(-1).min(-1)) (r = 0.475, p = 0.002). No significant main effect was detected between VO2peak (mL.kg(-1).min(-1)) dynamics (comparison with the previous age group data) and ACE I/D and ACTN3 R577X genotypes interactions (F = 0.571, p = 0.770 and F = 0.650 and p = 0.705, respectively) in all young skiers. Study results indicated a significantly higher frequency of the ACE ID and ACTN3 RR genotypes among Estonian young male skiers compared with the male control group. Significant genotype-related differences in dynamics of VO2peak during a 5 year period were not found. In the future, longitudinal research including different gene variants may contribute to a better understanding of the nature of endurance performance. Key pointsSignificantly higher prevalence of the ACE ID and the ACTN3 RR genotypes were found among Estonian young male skiers compared with the male control group, which may be an advantage for the explosive speed and power capacity in race skiing.A more remarkable trend of increase in VO2peak (mL.kg(-1).min(-1)) during the 5-year period was observed among male skiers with the ACTN3 XX genotype and among female skiers with the ACE ID genotype.No significant genotype-related associations in the dynamics of VO2peak were found during the 5-year period. PMID- 27274668 TI - Comparison of Ball-And-Racket Impact Force in Two-Handed Backhand Stroke Stances for Different-Skill-Level Tennis Players. AB - This study compared the kinetic roles of the upper extremities in racket impact force generation between the open stance (OS) and square stance (SS) for tennis players with different skill levels in two-handed backhand strokes. Twelve male tennis players were divided into an advanced group (AG) (L3-L2 skill level) and intermediate group (IG) (L7-L6 skill level), and their data were used in a three dimensional kinetic analysis. Their motions were captured using 21 reflective markers attached to anatomic landmarks for two-handed backhand stroke motion data collection. During the acceleration phase, significant differences were not observed between both stances, but they were observed between the groups with different skill levels for the force of the upper extremities (p = 0.027). The joint forces were significantly lower in the AG than in the IG. Players performing the SS had significantly larger pronation and supination of the wrist joint moment than those in the OS (p = 0.032) during the acceleration phase, irrespective of the playing level. Higher internal rotation moment after impact was observed at each joint, particularly among young intermediate tennis players, regardless of their stance. The AG demonstrated a higher joint force and moment at every joint compared with the IG at impact. Moreover, the AG demonstrated superior stroke efficiency and effectively reduced joint moment after impact and sports injury. Key pointsAdvanced players, regardless of open stance or square stance, have larger joint force and moment at each joint before ball impact resulting in better stroke efficiency and reduced chance of injury.Intermediate players, regardless of stance, have higher internal rotation moment at each joint instead of larger joint force as compared to advanced players before ball impact. The higher internal rotation moment will induce higher joint impact force which makes the player injury-prone.Young intermediate tennis players may want to avoid excessive follow-through movement after ball impact to prevent injury in their early career. PMID- 27274669 TI - Can Time Efficient Exercise Improve Cardiometabolic Risk Factors in Type 2 Diabetes? A Pilot Study. AB - Exercise is considered a cornerstone in the prevention and treatment of type 2 diabetes, but few individuals with type 2 diabetes exercise according to guidelines. We investigated the effect of two time efficient high intensity exercise interventions on exercise capacity, glycemic control and other cardiometabolic risk factors in patients with type 2 diabetes. Twenty-one individuals with type 2 diabetes were randomly assigned to low volume high intensity interval exercise (HIIE; 27 minutes/bout; 10x1-minute at 90 % of HRmax; n = 10) or extremely low volume sprint interval exercise (SIE; 10 minutes/bout; 2x20 seconds at maximum achievable intensity; n = 11) 3 days/week for 12 weeks. Aerobic exercise capacity (VO2peak), glycosylated hemoglobin (HbA1c), blood pressure and body composition were measured at baseline and post test. Both HIIE and SIE improved VO2peak (3.3 mL.min(-1).kg(-1), 10.4 %), p < 0.01, and 1.4 mL.min(-1).kg(-1) (4.6 %), p = 0.03, respectively). Only HIIE reduced body fat percentage (4.5 %, p = 0.04) and two minute heart rate recovery (11.0 bpm, p = 0.02). Neither HIIE nor SIE improved HbA1c. In conclusion, this study indicates that substantially lower exercise volumes than recommended in current guidelines can improve aerobic exercise capacity in individuals with type 2 diabetes. However, 12 weeks of time efficient high intensity exercise did not improve glycemic control, and interventions of longer duration should be investigated. Key pointsLow volume high-intensity interval exercise can improve peak oxygen uptake in previously sedentary individuals with type 2 diabetesThe weekly exercise volumes in the two intervention groups of 81 and 30 minutes respectively, is substantially lower than recommended in current exercise guidelines and could reduce the time-barrier associated with exercise among patients with type 2 diabetes.However, 12 weeks of structured, supervised low volume exercise did not improve glycemic control, indicating a need for exercise volumes or longer intervention period. PMID- 27274670 TI - Multi-Directional Sprint Training Improves Change-Of-Direction Speed and Reactive Agility in Young Highly Trained Soccer Players. AB - The aim of this study was to evaluate the effect of a repeated sprint training with multi-directional change-of-direction (COD) movements (RSmulti) compared to repeated shuttle sprints (RSS) on variables related to COD speed and reactive agility. Nineteen highly-trained male U15 soccer players were assigned into two groups performing either RSmulti or RSS. For both groups, each training session involved 20 repeated 15 s sprints interspersed with 30 s recovery. With RSmulti the COD movements were randomized and performed in response to a visual stimulus, while the RSS involved predefined 180 degrees COD movements. Before and following the six training sessions, performance in the Illinois agility test (IAT), COD speed in response to a visual stimulus, 20 m linear sprint time and vertical jumping height were assessed. Both groups improved their performance in the IAT (p < 0.01, ES = 1.13; p = 0.01, ES = 0.55). The COD speed in response to a visual stimulus improved with the RSmulti (p < 0.01, ES = 1.03), but not the RSS (p = 0.46, ES = 0.28). No differences were found for 20 m sprint time (P=0.73, ES = 0.07; p = 0.14, ES = 0.28) or vertical jumping height (p = 0.46, ES = 0.11; p = 0.29, ES = 0.12) for the RSmulti and RSS, respectively. In conclusion, performance in the IAT improved with the RSmulti as well as RSS. With the RSmulti however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility in young highly trained soccer players. Key pointsDuring soccer, the players perform repeated sprints involving multi-directional COD movements, while most of these turns and twists are not pre-planned but executed in response to an external stimulus, such as ball movement, several interacting opponents and changing game situations.Both groups improved performance in the IAT. With the RSmulti on the Speedcourt however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility.The Speedcourt could serve as a valuable method to design and individualize specific conditioning drills for young highly-trained soccer players. PMID- 27274671 TI - Does Physical Loading Affect The Speed and Accuracy of Tactical Decision-Making in Elite Junior Soccer Players? AB - A soccer player's capability to control and manage his behaviour in a game situation is a prerequisite, reflecting not only swift and accurate tactical decision-making, but also prompt implementation of a motor task during intermittent exercise conditions. The purpose of this study was to analyse the relationship between varying exercise intensity and the visual-motor response time and the accuracy of motor response in an offensive game situation in soccer. The participants (n = 42) were male, semi-professional, soccer players (M age 18.0 +/- 0.9 years) and trained five times a week. Each player performed four different modes of exercise intensity on the treadmill (motor inactivity, aerobic, intermittent and anaerobic activity). After the end of each exercise, visual-motor response time and accuracy of motor response were assessed. Players' motion was captured by digital video camera. ANOVA indicated no significant difference (p = 0.090) in the accuracy of motor response between the four exercise intensity modes. Practical significance (Z-test = 0.31) was found in visual-motor response time between exercise with dominant involvement of aerobic metabolism, and intense intermittent exercise. A medium size effect (Z-test = 0.34) was also found in visual-motor response time between exercise with dominant involvement of aerobic metabolism and exercise with dominant involvement of anaerobic metabolism, which was confirmed by ANOVA (897.02 +/- 57.46 vs. 940.95 +/- 71.14; p = 0.002). The results showed that different modes of exercise intensity do not adversely affect the accuracy of motor responses; however, high intensity exercise has a negative effect on visual-motor response time in comparison to moderate intensity exercise. Key pointsDifferent exercise intensity modes did not affect the accuracy of motor response.Anaerobic, highly intensive short-term exercise significantly decreased the visual-motor response time in comparison with aerobic exercise.Further research should focus on the assessment of VMRT from a player's real - field position view rather than a perspective view. PMID- 27274672 TI - The Influence of a Bout of Exertion on Novice Barefoot Running Dynamics. AB - Barefoot, forefoot strike (FFS) running has recently risen in popularity. Relative to shod, rear-foot strike (RFS) running, employing a FFS is associated with heightened triceps surae muscle activation and ankle mechanical demand. Novice to this pattern, it is plausible that habitually shod RFS runners exhibit fatigue to the triceps surae when acutely transitioning to barefoot running, thereby limiting their ability to attenuate impact. Therefore, the purpose was to determine how habitually shod RFS runners respond to an exertion bout of barefoot running, operationally defined as a barefoot run 20% of mean daily running distance. Twenty-one RFS runners performed novice barefoot running, before and after exertion. Ankle peak torque, triceps surae EMG median frequency, foot strike patterns, joint energy absorption, and loading rates were evaluated. Of the 21 runners, 6 maintained a RFS, 10 adopted a mid-foot strike (MFS), and 5 adopted a FFS during novice barefoot running. In-response to exertion, MFS and FFS runners demonstrated reductions in peak torque, median frequency, and ankle energy absorption, and an increase in loading rate. RFS runners demonstrated reductions in peak torque and loading rate. These results indicate that a short bout of running may elicit fatigue to novice barefoot runners, limiting their ability to attenuate impact. Key pointsIn response to exertion, novice barefoot runners demonstrate fatigue to their soleus.In response to exertion, novice barefoot runners demonstrate a reduction in ankle energy absorptionIn response to exertion, novice barefoot runners demonstrate an increase in loading rate. PMID- 27274673 TI - Association of Quality Physical Education Teaching with Students' Physical Fitness. AB - This study examined the extent to which four essential dimensions of quality physical education teaching (QPET) were associated with healthy levels of physical fitness in elementary school students. Participants were nine elementary PE teachers and 1, 201 fourth- and fifth-grade students who were enrolled in nine elementary schools. The students' physical fitness were assessed using four FITNESSGRAM tests. The PE teachers' levels of QPET were assessed using the Assessing Quality Teaching Rubrics (AQTR). The AQTR consisted of four essential dimensions including Task Design, Task Presentation, Class Management, and Instructional Guidance. Codes were confirmed through inter-rater reliability (82.4% and 84.5%). Data were analyzed through descriptive statistics, multiple R squared regression models, and independent sample t-tests. The four essential teaching dimensions of QPET were significantly associated with the students' cardiovascular endurance, muscular strength and endurance, and flexibility. However, they accounted for relatively low percentage of the total variance in PACER test, followed by Curl-up test, while explaining very low portions of the total variance in Push-up and Trunk Lift tests. This study indicated that the students who had experienced high level of QPET were more physically fit than their peers who did not have this experience in PACER and Curl-up tests, but not in Push-up and Trunk lift tests. In addition, the significant contribution of the four essential teaching dimensions to physical fitness components was gender specific. It was concluded that the four teaching dimensions of QPET were significantly associated with students' health-enhancing physical fitness. Key pointsAlthough Task Design, Task Presentation, Class Management, and Instructional Guidance has its unique and critical teaching components, each essential teaching dimensions is intertwined and immersed in teaching practices.Four essential teaching dimensions all significantly contributed to students' health-enhancing physical fitness.Implementation of QPET in a lesson plays more significant role in contributing to improving girls' cardiovascular endurance.Implementation of QPET in a lesson contributed significantly to improving boy's abdominal, upper-body, and back extensor muscular strength and endurance as well as flexibility. PMID- 27274674 TI - Relationship between Leg Mass, Leg Composition and Foot Velocity on Kicking Accuracy in Australian Football. AB - Kicking a ball accurately over a desired distance to an intended target is arguably the most important skill to acquire in Australian Football. Therefore, understanding the potential mechanisms which underpin kicking accuracy is warranted. The aim of this study was to examine the relationship between leg mass, leg composition and foot velocity on kicking accuracy in Australian Football. Thirty-one Australian Footballers (n = 31; age: 22.1 +/- 2.8 years; height: 1.81 +/- 0.07 m; weight: 85.1 +/- 13.0 kg; BMI: 25.9 +/- 3.2) each performed ten drop punt kicks over twenty metres to a player target. Athletes were separated into accurate (n = 15) and inaccurate (n = 16) kicking groups. Leg mass characteristics were assessed using whole body DXA scans. Foot velocity was determined using a ten-camera optoelectronic, three-dimensional motion capture system. Interactions between leg mass and foot velocity evident within accurate kickers only (r = -0.670 to -0.701). Relative lean mass was positively correlated with kicking accuracy (r = 0.631), while no relationship between foot velocity and kicking accuracy was evident in isolation (r = -0.047 to -0.083). Given the evident importance of lean mass, and its interaction with foot velocity for accurate kickers; future research should explore speed-accuracy, impulse variability, limb co-ordination and foot-ball interaction constructs in kicking using controlled with-in subject studies to examine the effects of resistance training and skill acquisition programs on the development of kicking accuracy. Key pointsAccurate kickers expressed a very strong inverse relationship between leg mass and foot velocity. Inaccurate kickers were unable to replicate this, with greater volatility in their performance, indicating an ability of accurate kickers to mediate foot velocity to compensate for leg mass in order to deliver the ball over the required distance.Accurate kickers exhibited larger quantities of relative lean mass and lower quantities of relative fat mass in their kicking leg. Higher relative lean mass reduces the relative muscular impulses required to produce a given action, allowing greater limb control with proportionately reduced volitional effort.Kicking accuracy was unable to be explained by either foot velocity or leg mass in isolation; rather, it was the co-contribution and interrelation of these characteristics which were the discriminatory factors between accurate and inaccurate kickers. PMID- 27274675 TI - Effect of Semi-Rigid and Soft Ankle Braces on Static and Dynamic Postural Stability in Young Male Adults. AB - Ankle braces have been suggested to protect ankle joints from a sprain by restricting inversion and improving proprioception. However, the difference in effects between a semi-rigid brace and a soft brace regarding dynamic postural control after landing is not known. The aim of the present study was to compare the effect of soft (SB) and semi-rigid (SRB) ankle braces on static and dynamic postural stability in healthy young men. Altogether, 21 male adults (mean age 24.0 +/- 1.5 years) were assessed for one leg while wearing non-brace (NB), SB or SRB. Balance in single-limb stance on a single-force platform with open eyes and closed eyes were assessed for the non-dominant leg under SB, SRB, and NB conditions. Locus length/second (mm/s) and the enveloped area (mm.s(-2)) surrounded by the circumference of the wave pattern during postural sway were calculated. For assessing dynamic postural stability, the participant jumped and landed on one leg on a force platform, and the Dynamic Postural Stability Index (DPSI) and the maximum vertical ground reaction force (vGRFmax) were measured. The data were compared among the three conditions with repeated-measures analysis of variance. The correlations between locus length/second, enveloped area, DPSI values (DPSI, Anterior-Posterior Stability Index, Medial-Lateral Stability Index, and Vertical Stability Index), and vGRFmax were then calculated. The results indicated that locus length/second and enveloped area with open eyes and closed eyes were not significantly different for each condition. However, a significant lower in the DPSI and Vertical Stability Index were observed with the SRB in comparison to the SB and NB. A significant improvement in vGRFmax was also observed with the SRB in comparison to NB. SRB demonstrated a positive effect on dynamic postural stability after landing on a single leg and may improve balance by increasing dynamic postural stability. Key pointsThis study examined the effect of ankle braces on healthy young individuals during dynamic postural stability using the DPSI.The semi-rigid brace improved dynamic postural stability compared with the soft brace and no brace. PMID- 27274676 TI - The Effects of Two Self-Regulation Interventions to Increase Self-Efficacy and Group Exercise Behavior in Fitness Clubs. AB - Studies on the adoption and maintenance of group exercise behavior are scarce. The objective of this study is to test two self-efficacy based interventions to increase barrier self-efficacy and group exercise behavior. In total 122 participants (Mage 42.02 yr.; SD 12.29; 67% females) were recruited and randomly assigned to one control and two experimental groups. The control group was limited to participate in one virtual group exercise program only (group 1). The first experimental group was able to self-set their activities and participate in multiple group exercise programs (group 2). The second experimental group received an additional monthly coaching protocol to manage self-set goals (group 3). A validated scale for barrier self-efficacy was used, group exercise sessions were measured and drop-out rates were registered. An ANOVA indicated that mean amount of sessions of group 1 and 3, and 2 and 3 differed significantly (p < 0.05) in 12 weeks. Descriptive statistics demonstrate mean group exercise sessions over the total of 12 weeks of 2.74 (SD 4.65) in the control group; 4.75 (SD 6.08) in the first experimental group, and 12.25 (SD 9.07) for the second experimental group. Regression analysis indicated that self-efficacy at 8-weeks explained the highest variance in overall group exercise sessions (R(2) = 0.18; p < 0.05). Overall drop-out rates were 88% in group 1, 78% in group 2 and 48% in group 3. The results showed that group exercise behavior can significantly be improved by a coaching protocol on self-set goals. Future research should address the effectiveness of self-set activities and self-set goals for a longer period of time and in other types of exercise programs. Key pointsApproximately 144 million individuals exercise in fitness clubs worldwide.About 50% participate in at least one group exercise program and 23% participate only in group exercise classes with instructor.Research on attendance and exercise behavior in fitness clubs is limited but there are strong indications that the frequencies are low.This study demonstrates that group exercise behavior in fitness clubs can be improved significantly by a coaching protocol on self-set goals based on tenets of self-efficacy theory. PMID- 27274677 TI - Salivary Biomarker Responses to Two Final Matches in Women's Professional Football. AB - The aim of this study was to examine the link between salivary concentrations of cortisol, testosterone, immunoglobulin A (IgA) and the rate of perceived exertion (RPE) as a measure of internal load after two final matches played 3 days apart by professional women football players. Saliva samples were taken before and after the two matches (M1, M2). RPE was used to monitor the exercise intensity after each match. Testosterone concentrations increased after each match (M1: +42%, p = 0.002; M2: +50%, p < 0.001) while cortisol increased only after M1 (+116%, p < 0.001). The testosterone-to-cortisol ratio decreased only after M1 ( 32.4%, p < 0.001). IgA concentration did not change after any match. Testosterone concentrations were correlated with IgA concentrations after each match (M1: R = 0.59, p = 0.008; M2: R=0.51, p = 0.02). RPE was correlated with cortisol concentrations after M1 (R = 0.57; p = 0.01), but not after M2 (R = 0.38; p = 0.07). All these results suggest that salivary cortisol and testosterone concentrations increase especially after the first match of a final, without affecting IgA levels. We speculate that increased testosterone concentration in women after football matches may play a protecting role against immune suppression usually observed after intense exercise. Key pointsIn our sample space, IgA concentrations did not change for teams even, before and after separated match. Suggesting that salivary IgA determinations after physical activities remain under debate.Testosterone concentrations were the only one hormone showing a consequent increase in both matches after physical activity carrying.The T/C ratio decrease only after M1 according with a higher cortisol level reach after M1 get-together, suggesting a differential impact over anxiety associated team performance. So M2 play gives a more stable psychological state. PMID- 27274678 TI - Sex-Related Differences in Self-Paced All Out High-Intensity Intermittent Cycling: Mechanical and Physiological Responses. AB - The purpose of this study was to compare sex-related responses to a self-paced all out high-intensity intermittent exercise (HIIE). 9 women and 10 men were submitted to a maximal incremental test (to determine maximum aerobic power - MAP and VO2peak), and an HIIE cycling (60x8s:12s, effort:pause). During the protocol the mean value of VO2 and heart rate for the entire exercise (VO2total and HRtotal) as well as the values only in the effort or pause (VO2effort, VO2pause and HReffort and HRpause) relative to VO2peak were measured. Anaerobic power reserve (APR), blood lactate [La] and the respiratory exchange ratio (RER) were also measured. These variables were compared between men and women using the unpaired t test. Men used greater APR (109 +/- 12%MAP vs 92 +/- 6%MAP) with similar VO2total (74 +/- 7 vs 78 +/- 8% VO2peak), however, when effort and pause were analysed separately, VO2effort (80 +/- 9 vs 80 +/- 5%VO2peak) was similar between sexes, while VO2pause was lower in men (69 +/- 6% vs 77 +/- 11% VO2peak, respectively). Women presented lower power decrement (30 +/- 11 vs 11 +/- 3%), RER (1.04 +/- 0.03 vs 1.00 +/- 0.02) and [La]peak (8.6 +/- 0.9 vs 5.9 +/- 2.3 mmol.L(-1)). Thus, we can conclude that men self-paced HIIE at higher APR but with the same cardiovascular/aerobic solicitation as women. Key pointsMen self paced high-intensity intermittent exercise at higher intensities than women.Men utilized greater anaerobic power reserve than women.Men and women had same cardiovascular solicitation. PMID- 27274679 TI - Effect of Wearing the Elevation Training Mask on Aerobic Capacity, Lung Function, and Hematological Variables. AB - Altitude training and respiratory muscle training (RMT) have been reported to improve performance in elite and well-trained athletes. Several devices (altitude and RMT) have been developed to help athletes gain the competitive edge. The Elevation Training Mask 2.0 (ETM) purportedly simulates altitude training and has been suggested to increase aerobic capacity (VO2max), endurance performance, and lung function. Twenty-four moderately trained subjects completed 6 weeks of high intensity cycle ergometer training. Subjects were randomized into a mask (n = 12) or control (n = 12) group. Pre and post-training tests included VO2max, pulmonary function, maximal inspiration pressure, hemoglobin and hematocrit. No significant differences were found in pulmonary function or hematological variables between or within groups. There was a significant improvement in VO2max and PPO in both the control (13.5% and 9.9%) and mask (16.5% and 13.6%) groups. There was no difference in the magnitude of improvement between groups. Only the mask group had significant improvements in ventilatory threshold (VT) (13.9%), power output (PO) at VT (19.3%), respiratory compensation threshold (RCT) (10.2%), and PO at RCT (16.4%) from pre to post-testing. The trends for improvements in VT and PO at VT between groups were similar to improvements in RCT and PO at RCT, but did not reach statistical significance (VT p = 0.06, PO at VT p = 0.170). Wearing the ETM while participating in a 6-week high-intensity cycle ergometer training program does not appear to act as a simulator of altitude, but more like a respiratory muscle training device. Wearing the ETM may improve specific markers of endurance performance beyond the improvements seen with interval training alone. Key pointsWearing the ETM during a 6-week high-intensity cycle ergometer training program may improve performance variables, such as VO2max, PPO, VT, PO at VT, RCT and PO at RCT.Wearing the ETM did not improve lung function, inspiratory muscle strength, or stimulate changes in hemoglobin or hematocrit levels.The ETM does not simulate altitude, but works more like an respiratory training device. PMID- 27274680 TI - Self-Medication Practice among Amateur Runners: Prevalence and Associated Factors. PMID- 27274681 TI - Normobaric Hypoxia Exposure during Low Altitude Stay and Performance of Elite Level Race-Walkers. PMID- 27274682 TI - Evaluating Service Organization Models: The Relevance and Methodological Challenges of a Configurational Approach. AB - Based on the example of the evaluation of service organization models, this article shows how a configurational approach overcomes the limits of traditional methods which for the most part have studied the individual components of various models considered independently of one another. These traditional methods have led to results (observed effects) that are difficult to interpret. The configurational approach, in contrast, is based on the hypothesis that effects are associated with a set of internally coherent model features that form various configurations. These configurations, like their effects, are context-dependent. We explore the theoretical basis of the configuration approach in order to emphasize its relevance, and discuss the methodological challenges inherent in the application of this approach through an in-depth analysis of the scientific literature. We also propose methodological solutions to these challenges. We illustrate from an example how a configurational approach has been used to evaluate primary care models. Finally, we begin a discussion on the implications of this new evaluation approach for the scientific and decision-making communities. PMID- 27274683 TI - The detection of flaws in austenitic welds using the decomposition of the time reversal operator. AB - The non-destructive testing of austenitic welds using ultrasound plays an important role in the assessment of the structural integrity of safety critical structures. The internal microstructure of these welds is highly scattering and can lead to the obscuration of defects when investigated by traditional imaging algorithms. This paper proposes an alternative objective method for the detection of flaws embedded in austenitic welds based on the singular value decomposition of the time-frequency domain response matrices. The distribution of the singular values is examined in the cases where a flaw exists and where there is no flaw present. A lower threshold on the singular values, specific to austenitic welds, is derived which, when exceeded, indicates the presence of a flaw. The detection criterion is successfully implemented on both synthetic and experimental data. The datasets arising from welds containing a flaw are further interrogated using the decomposition of the time-reversal operator (DORT) method and the total focusing method (TFM), and it is shown that images constructed via the DORT algorithm typically exhibit a higher signal-to-noise ratio than those constructed by the TFM algorithm. PMID- 27274684 TI - Nonlinear regularization operators as derived from the micromorphic approach to gradient elasticity, viscoplasticity and damage. AB - The construction of regularization operators presented in this work is based on the introduction of strain or damage micromorphic degrees of freedom in addition to the displacement vector and of their gradients into the Helmholtz free energy function of the constitutive material model. The combination of a new balance equation for generalized stresses and of the micromorphic constitutive equations generates the regularization operator. Within the small strain framework, the choice of a quadratic potential w.r.t. the gradient term provides the widely used Helmholtz operator whose regularization properties are well known: smoothing of discontinuities at interfaces and boundary layers in hardening materials, and finite width localization bands in softening materials. The objective is to review and propose nonlinear extensions of micromorphic and strain/damage gradient models along two lines: the first one introducing nonlinear relations between generalized stresses and strains; the second one envisaging several classes of finite deformation model formulations. The generic approach is applicable to a large class of elastoviscoplastic and damage models including anisothermal and multiphysics coupling. Two standard procedures of extension of classical constitutive laws to large strains are combined with the micromorphic approach: additive split of some Lagrangian strain measure or choice of a local objective rotating frame. Three distinct operators are finally derived using the multiplicative decomposition of the deformation gradient. A new feature is that a free energy function depending solely on variables defined in the intermediate isoclinic configuration leads to the existence of additional kinematic hardening induced by the gradient of a scalar micromorphic variable. PMID- 27274685 TI - Numerical solution of acoustic scattering by finite perforated elastic plates. AB - We present a numerical method to compute the acoustic field scattered by finite perforated elastic plates. A boundary element method is developed to solve the Helmholtz equation subjected to boundary conditions related to the plate vibration. These boundary conditions are recast in terms of the vibration modes of the plate and its porosity, which enables a direct solution procedure. A parametric study is performed for a two-dimensional problem whereby a cantilevered perforated elastic plate scatters sound from a point quadrupole near the free edge. Both elasticity and porosity tend to diminish the scattered sound, in agreement with previous work considering semi-infinite plates. Finite elastic plates are shown to reduce acoustic scattering when excited at high Helmholtz numbers k0 based on the plate length. However, at low k0, finite elastic plates produce only modest reductions or, in cases related to structural resonance, an increase to the scattered sound level relative to the rigid case. Porosity, on the other hand, is shown to be more effective in reducing the radiated sound for low k0. The combined beneficial effects of elasticity and porosity are shown to be effective in reducing the scattered sound for a broader range of k0 for perforated elastic plates. PMID- 27274686 TI - A personal perspective on modelling the climate system. AB - Given their increasing relevance for society, I suggest that the climate science community itself does not treat the development of error-free ab initio models of the climate system with sufficient urgency. With increasing levels of difficulty, I discuss a number of proposals for speeding up such development. Firstly, I believe that climate science should make better use of the pool of post-PhD talent in mathematics and physics, for developing next-generation climate models. Secondly, I believe there is more scope for the development of modelling systems which link weather and climate prediction more seamlessly. Finally, here in Europe, I call for a new European Programme on Extreme Computing and Climate to advance our ability to simulate climate extremes, and understand the drivers of such extremes. A key goal for such a programme is the development of a 1 km global climate system model to run on the first exascale supercomputers in the early 2020s. PMID- 27274687 TI - Sintering of viscous droplets under surface tension. AB - We conduct experiments to investigate the sintering of high-viscosity liquid droplets. Free-standing cylinders of spherical glass beads are heated above their glass transition temperature, causing them to densify under surface tension. We determine the evolving volume of the bead pack at high spatial and temporal resolution. We use these data to test a range of existing models. We extend the models to account for the time-dependent droplet viscosity that results from non isothermal conditions, and to account for non-zero final porosity. We also present a method to account for the initial distribution of radii of the pores interstitial to the liquid spheres, which allows the models to be used with no fitting parameters. We find a good agreement between the models and the data for times less than the capillary relaxation timescale. For longer times, we find an increasing discrepancy between the data and the model as the Darcy outgassing time-scale approaches the sintering timescale. We conclude that the decreasing permeability of the sintering system inhibits late-stage densification. Finally, we determine the residual, trapped gas volume fraction at equilibrium using X-ray computed tomography and compare this with theoretical values for the critical gas volume fraction in systems of overlapping spheres. PMID- 27274688 TI - The development of biofilm architecture. AB - We extend the one-dimensional polymer solution theory of bacterial biofilm growth described by Winstanley et al. (2011 Proc. R. Soc. A467, 1449-1467 (doi:10.1098/rspa.2010.0327)) to deal with the problem of the growth of a patch of biofilm in more than one lateral dimension. The extension is non-trivial, as it requires consideration of the rheology of the polymer phase. We use a novel asymptotic technique to reduce the model to a free-boundary problem governed by the equations of Stokes flow with non-standard boundary conditions. We then consider the stability of laterally uniform biofilm growth, and show that the model predicts spatial instability; this is confirmed by a direct numerical solution of the governing equations. The instability results in cusp formation at the biofilm surface and provides an explanation for the common observation of patterned biofilm architectures. PMID- 27274689 TI - Frequency-dependent scaling from mesoscale to macroscale in viscoelastic random composites. AB - This paper investigates the scaling from a statistical volume element (SVE; i.e. mesoscale level) to representative volume element (RVE; i.e. macroscale level) of spatially random linear viscoelastic materials, focusing on the quasi-static properties in the frequency domain. Requiring the material statistics to be spatially homogeneous and ergodic, the mesoscale bounds on the RVE response are developed from the Hill-Mandel homogenization condition adapted to viscoelastic materials. The bounds are obtained from two stochastic initial-boundary value problems set up, respectively, under uniform kinematic and traction boundary conditions. The frequency and scale dependencies of mesoscale bounds are obtained through computational mechanics for composites with planar random chessboard microstructures. In general, the frequency-dependent scaling to RVE can be described through a complex-valued scaling function, which generalizes the concept originally developed for linear elastic random composites. This scaling function is shown to apply for all different phase combinations on random chessboards and, essentially, is only a function of the microstructure and mesoscale. PMID- 27274690 TI - Experimental demonstration of information to energy conversion in a quantum system at the Landauer limit. AB - Landauer's principle sets fundamental thermodynamical constraints for classical and quantum information processing, thus affecting not only various branches of physics, but also of computer science and engineering. Despite its importance, this principle was only recently experimentally considered for classical systems. Here we employ a nuclear magnetic resonance set-up to experimentally address the information to energy conversion in a quantum system. Specifically, we consider a three nuclear spins [Formula: see text] (qubits) molecule-the system, the reservoir and the ancilla-to measure the heat dissipated during the implementation of a global system-reservoir unitary interaction that changes the information content of the system. By employing an interferometric technique, we were able to reconstruct the heat distribution associated with the unitary interaction. Then, through quantum state tomography, we measured the relative change in the entropy of the system. In this way, we were able to verify that an operation that changes the information content of the system must necessarily generate heat in the reservoir, exactly as predicted by Landauer's principle. The scheme presented here allows for the detailed study of irreversible entropy production in quantum information processors. PMID- 27274691 TI - On the axisymmetric stability of heated supersonic round jets. AB - We perform an inviscid, spatial stability analysis of supersonic, heated round jets with the mean properties assumed uniform on either side of the jet shear layer, modelled here via a cylindrical vortex sheet. Apart from the hydrodynamic Kelvin-Helmholtz (K-H) wave, the spatial growth rates of the acoustically coupled supersonic and subsonic instability waves are computed for axisymmetric conditions (m=0) to analyse their role on the jet stability, under increased heating and compressibility. With the ambient stationary, supersonic instability waves may exist for any jet Mach number Mj >=2, whereas the subsonic instability waves, in addition, require the core-to-ambient flow temperature ratio Tj /To >1. We show, for moderately heated jets at Tj /To >2, the acoustically coupled instability modes, once cut on, to govern the overall jet stability with the K-H wave having disappeared into the cluster of acoustic modes. Sufficiently high heating makes the subsonic modes dominate the jet near-field dynamics, whereas the supersonic instability modes form the primary Mach radiation at far field. PMID- 27274692 TI - Optimality of general lattice transformations with applications to the Bain strain in steel. AB - This article provides a rigorous proof of a conjecture by E. C. Bain in 1924 on the optimality of the so-called Bain strain based on a criterion of least atomic movement. A general framework that explores several such optimality criteria is introduced and employed to show the existence of optimal transformations between any two Bravais lattices. A precise algorithm and a graphical user interface to determine this optimal transformation is provided. Apart from the Bain conjecture concerning the transformation from face-centred cubic to body-centred cubic, applications include the face-centred cubic to body-centred tetragonal transition as well as the transformation between two triclinic phases of terephthalic acid. PMID- 27274693 TI - Stored electromagnetic energy and quality factor of radiating structures. AB - This paper deals with the old yet unsolved problem of defining and evaluating the stored electromagnetic energy-a quantity essential for calculating the quality factor, which reflects the intrinsic bandwidth of the considered electromagnetic system. A novel paradigm is proposed to determine the stored energy in the time domain leading to the method, which exhibits positive semi-definiteness and coordinate independence, i.e. two key properties actually not met by the contemporary approaches. The proposed technique is compared with an up-to-date frequency domain method that is extensively used in practice. Both concepts are discussed and compared on the basis of examples of varying complexity. PMID- 27274694 TI - The Born-Infeld vortices induced from a generalized Higgs mechanism. AB - We construct self-dual Born-Infeld vortices induced from a generalized Higgs mechanism. Two specific models of the theory are of focused interest where the Higgs potential is either of a |phi|4- or |phi|6-type. For the |phi|4-model, we obtain a sharp existence and uniqueness theorem for doubly periodic and planar vortices. For doubly periodic solutions, a necessary and sufficient condition for the existence is explicitly derived in terms of the vortex number, the Born Infeld parameter, and the size of the periodic lattice domain. For the |phi|6 model, we show that both topological and non-topological vortices are present. This new phenomenon distinguishes the model from the classical Born-Infeld-Higgs theory studied earlier in the literature. A series of results regarding doubly periodic, topological, and non-topological vortices in the |phi|6-model are also established. PMID- 27274695 TI - Lamb-type waves generated by a cylindrical bubble oscillating between two planar elastic walls. AB - The volume oscillation of a cylindrical bubble in a microfluidic channel with planar elastic walls is studied. Analytical solutions are found for the bulk scattered wave propagating in the fluid gap and the surface waves of Lamb-type propagating at the fluid-solid interfaces. This type of surface wave has not yet been described theoretically. A dispersion equation for the Lamb-type waves is derived, which allows one to evaluate the wave speed for different values of the channel height h. It is shown that for hStrata X>C-18. From the results, the hydrophobicity degree of the samples depended on the type and number of carboxylic acids that were removed by the SPE cartridges. PMID- 27274732 TI - Idiopathic Pulmonary Vein Thrombus Extending into Left Atrium: A Case Report and Review of the Literature. AB - Pulmonary vein thrombosis (PVT) is rather an uncommon condition which presents nonspecifically and is usually associated with lung malignancy and major pulmonary surgery. Rarely could no cause be found. It causes increased pulmonary venous pressure leading to pulmonary arterial vasoconstriction and subsequent pulmonary arterial hypertension and subsequently can cause cor pulmonale if not addressed in timely fashion. Other associated complications like peripheral embolization and stroke have also been reported. This case emphasizes the importance of maintaining high index of clinical suspicion especially when CT pulmonary angiogram is negative for pulmonary embolism. PMID- 27274733 TI - Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease. AB - Stem cell-derived neurons from various source materials present unique model systems to examine the fundamental properties of central nervous system (CNS) development as well as the molecular underpinnings of disease phenotypes. In order to more accurately assess potential therapies for neurological disorders, multiple strategies have been employed in recent years to produce neuronal populations that accurately represent in vivo regional and transmitter phenotypes. These include new technologies such as direct conversion of somatic cell types into neurons and glia which may accelerate maturation and retain genetic hallmarks of aging. In addition, novel forms of genetic manipulations have brought human stem cells nearly on par with those of rodent with respect to gene targeting. For neurons of the CNS, the ultimate phenotypic characterization lies with their ability to recapitulate functional properties such as passive and active membrane characteristics, synaptic activity, and plasticity. These features critically depend on the coordinated expression and localization of hundreds of ion channels and receptors, as well as scaffolding and signaling molecules. In this review I will highlight the current state of knowledge regarding functional properties of human stem cell-derived neurons, with a primary focus on pluripotent stem cells. While significant advances have been made, critical hurdles must be overcome in order for this technology to support progression toward clinical applications. PMID- 27274735 TI - Cell-Based Strategies for Meniscus Tissue Engineering. AB - Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID- 27274736 TI - The Effect of MSCs Derived from the Human Umbilical Cord Transduced by Fibroblast Growth Factor-20 on Parkinson's Disease. AB - Cell therapy is a potential therapeutic approach for Parkinson's disease (PD). Mesenchymal stem cells derived from the human umbilical cord (hUC-MSCs) give priority to PD patients because of multiple advantages. The appropriate gene transduction of hUC-MSC before transplantation is a promising procedure for cell therapy. Fibroblast growth factor-20 (FGF-20) has been shown to protect dopaminergic neurons against a range of toxic insults in vitro. In this study, the hUC-MSCs were gene transduced with FGF-20, and then we transplanted them into the PD mice model. The results showed that MSC-FGF-20 treatment obviously improved the behavior of PD, accompanied by the increase of tyrosine carboxylase- (TH-) positive cell and dopamine (DA). Furtherly, immunohistochemistry disclosed that MSC-FGF-20 obviously promoted the degradation of nuclear factor-kappaB (NF kappaB), a transcription factor that controls genes encoding proinflammatory cytokines, highly expressed in the nigrostriatal dopaminergic regions in PD patients. Therefore, MSC-FGF-20 has a potential for improving PD, closely related to the degradation of NF-kappaB. PMID- 27274734 TI - Environmental Ligands of the Aryl Hydrocarbon Receptor and Their Effects in Models of Adult Liver Progenitor Cells. AB - The toxicity of environmental and dietary ligands of the aryl hydrocarbon receptor (AhR) in mature liver parenchymal cells is well appreciated, while considerably less attention has been paid to their impact on cell populations exhibiting phenotypic features of liver progenitor cells. Here, we discuss the results suggesting that the consequences of the AhR activation in the cellular models derived from bipotent liver progenitors could markedly differ from those in hepatocytes. In contact-inhibited liver progenitor cells, the AhR agonists induce a range of effects potentially linked with tumor promotion. They can stimulate cell cycle progression/proliferation and deregulate cell-to-cell communication, which is associated with downregulation of proteins forming gap junctions, adherens junctions, and desmosomes (such as connexin 43, E-cadherin, beta-catenin, and plakoglobin), as well as with reduced cell adhesion and inhibition of intercellular communication. At the same time, toxic AhR ligands may affect the activity of the signaling pathways contributing to regulation of liver progenitor cell activation and/or differentiation, such as downregulation of Wnt/beta-catenin and TGF-beta signaling, or upregulation of transcriptional targets of YAP/TAZ, the effectors of Hippo signaling pathway. These data illustrate the need to better understand the potential role of liver progenitors in the AhR-mediated liver carcinogenesis and tumor promotion. PMID- 27274739 TI - Special Series on the Use of Technology in the Delivery of Child and Youth Mental Health Services and Supports. PMID- 27274737 TI - A Systematic Comparison Identifies an ATP-Based Viability Assay as Most Suitable Read-Out for Drug Screening in Glioma Stem-Like Cells. AB - Serum-free culture methods for patient-derived primary glioma cultures, selecting for glioma stem-like cells (GSCs), are becoming the gold standard in neurooncology research. These GSCs can be implemented in drug screens to detect patient-specific responses, potentially bridging the translational gap to personalized medicine. Since numerous compounds are available, a rapid and reliable readout for drug efficacies is required. This can be done using approaches that measure viability, confluency, cytotoxicity, or apoptosis. To determine which assay is best suitable for drug screening, 10 different assays were systematically tested on established glioma cell lines and validated on a panel of GSCs. General applicability was assessed using distinct treatment modalities, being temozolomide, radiation, rapamycin, and the oncolytic adenovirus Delta24-RGD. The apoptosis and cytotoxicity assays did not unequivocally detect responses and were excluded from further testing. The NADH- and ATP-based viability assays revealed comparable readout for all treatments; however, the latter had smaller standard deviations and direct readout. Importantly, drugs that interfere with cell metabolism require alternative techniques such as confluency monitoring to accurately measure treatment effects. Taken together, our data suggest that the combination of ATP luminescence assays with confluency monitoring provides the most specific and reproducible readout for drug screening on primary GSCs. PMID- 27274740 TI - SSRIs-Related Behavioural Syndromes in Children and Adolescents. PMID- 27274738 TI - Biomaterial Applications in Cell-Based Therapy in Experimental Stroke. AB - Stroke is an important health issue corresponding to the second cause of mortality and first cause of severe disability with no effective treatments after the first hours of onset. Regenerative approaches such as cell therapy provide an increase in endogenous brain structural plasticity but they are not enough to promote a complete recovery. Tissue engineering has recently aroused a major interesting development of biomaterials for use into the central nervous system. Many biomaterials have been engineered based on natural compounds, synthetic compounds, or a mix of both with the aim of providing polymers with specific properties. The mechanical properties of biomaterials can be exquisitely regulated forming polymers with different stiffness, modifiable physical state that polymerizes in situ, or small particles encapsulating cells or growth factors. The choice of biomaterial compounds should be adapted for the different applications, structure target, and delay of administration. Biocompatibilities with embedded cells and with the host tissue and biodegradation rate must be considerate. In this paper, we review the different applications of biomaterials combined with cell therapy in ischemic stroke and we explore specific features such as choice of biomaterial compounds and physical and mechanical properties concerning the recent studies in experimental stroke. PMID- 27274742 TI - Web-Based and Mobile Suicide Prevention Interventions for Young People: A Systematic Review. AB - OBJECTIVE: Suicide is a significant public health issue, and is especially concerning in adolescents and young adults, who are over-represented both in attempts and completed suicide. Emerging technologies represent a promising new approach to deliver suicide prevention interventions to these populations. The current systematic review aims to identify online and mobile psychosocial suicide prevention interventions for young people, and evaluate the effectiveness of these interventions. METHOD: PsycINFO, Medline, Embase and The Cochrane Library were electronically searched for all articles published between January, 2000 and May, 2015. Peer-reviewed journal articles reporting on interventions for young people aged 12-25 years with suicidality as a primary outcome were eligible for inclusion. No exclusions were placed on study design. RESULTS: One study met inclusion criteria, and found significant reductions in the primary outcome of suicidal ideation, as well as depression and hopelessness. Two relevant protocol papers of studies currently underway were also identified. CONCLUSIONS: There is a paucity of current evidence for online and mobile interventions for suicide prevention in youth. More high quality empirical evidence is required to determine the effectiveness of these novel approaches to improving suicide outcomes in young people. PMID- 27274743 TI - Online and Social Media Suicide Prevention Interventions for Young People: A Focus on Implementation and Moderation. AB - OBJECTIVE: Suicide remains a major global public health issue for young people. The reach and accessibility of online and social media-based interventions herald a unique opportunity for suicide prevention. To date, the large body of research into suicide prevention has been undertaken atheoretically. This paper provides a rationale and theoretical framework (based on the interpersonal theory of suicide), and draws on our experiences of developing and testing online and social media-based interventions. METHOD: The implementation of three distinct online and social media-based intervention studies, undertaken with young people at risk of suicide, are discussed. We highlight the ways that these interventions can serve to bolster social connectedness in young people, and outline key aspects of intervention implementation and moderation. RESULTS: Insights regarding the implementation of these studies include careful protocol development mindful of risk and ethical issues, establishment of suitably qualified teams to oversee development and delivery of the intervention, and utilisation of key aspects of human support (i.e., moderation) to encourage longer-term intervention engagement. CONCLUSIONS: Online and social media-based interventions provide an opportunity to enhance feelings of connectedness in young people, a key component of the interpersonal theory of suicide. Our experience has shown that such interventions can be feasibly and safely conducted with young people at risk of suicide. Further studies, with controlled designs, are required to demonstrate intervention efficacy. PMID- 27274744 TI - Omega-6 to Omega-3 Fatty Acid Ratio in Patients with ADHD: A Meta-Analysis. AB - OBJECTIVE: Omega-3 and omega-6 fatty acids have been shown to be deficient in individuals with attention deficit/hyperactivity disorder compared to controls (Hawkey & Nigg, 2014). Clinical trials of omega-3 and omega-6 supplements as treatment for ADHD have demonstrated minimal efficacy (Bloch & Qawasmi, 2011; Gillies, Sinn, Lad, Leach, & Ross, 2011; Hawkey & Nigg, 2014; Puri & Martins, 2014; Sonuga-Barke et al., 2013). Existing trials have analyzed omega-3 and omega 6 separately although the tissue ratio of these fatty acids (n6/n3) may be more important than absolute levels of either. The objective of this study was to determine the relationship between blood n6/n3 and arachidonic acid to eicosapentaenoic acid (AA/EPA), to ADHD symptoms. METHOD: A systematic literature review identified original articles measuring blood n6/n3 or AA/EPA ratio in children and youth with ADHD, compared to controls without ADHD. Three databases were searched. Blood n6/n3, and AA/EPA ratios were compared between individuals with ADHD and controls. Results were pooled across studies using quantitative synthesis. RESULTS: Five articles met inclusion criteria for the meta-analysis. The pooled mean difference between patients with ADHD and controls was 1.97 (0.90 3.04) for n6/n3 (n=5 studies, I(2) 83%) and 8.25 (5.94-10.56) for AA/EPA (n=3 studies, I(2) 0%). CONCLUSIONS: Children and youth with ADHD have elevated ratios of both blood n6/n3 and AA/EPA fatty acids compared to controls. Thus an elevated n6/n3, and more specifically AA/EPA, ratio may represent the underlying disturbance in essential fatty acid levels in patients with ADHD. These findings have implications for the development of future interventions using essential fatty acids to treat ADHD, and for the use of these ratios as biomarkers for titrating and monitoring ADHD treatment with essential fatty acids. PMID- 27274745 TI - Links of Adolescents Identity Development and Relationship with Peers: A Systematic Literature Review. AB - OBJECTIVE: According to Erik Erikson, the main task of adolescents is to solve the crisis of identity versus role confusion. Research has shown that a stable and strong sense of identity is associated with better mental health of adolescents. Good relationships with peers are also linked with better emotional and psychological well-being of adolescents. However, there is a lack of reviews of studies in the scientific literature examining the relationship between the adolescents' identity development and relationships with peers. The aims of this article were to analyze links between adolescent identity development and relationships with peers identified from a literature review, summarize the results, and discuss the theoretical factors that may predict these relationships. METHOD: A systematic literature review. RESULTS: Analysis of findings from the systematic literature review revealed that a good relationship with peers is positively related to adolescent identity development, but empirical research in this area is extremely limited. CONCLUSIONS: The links between adolescents' identity development and their relationship with peers are not completely clear. The possible intermediate factors that could determine the relationship between adolescent identity development and their relationships with peers are discussed. Further empirical researches is needed in this area. PMID- 27274747 TI - Whole Genome Sequencing as a Genetic Test for Autism Spectrum Disorder: From Bench to Bedside and then Back Again. AB - Autism spectrum disorder (ASD) is characterized by repetitive patterns of behaviour and impairments in social interactions and communication abilities. Although ASD is a heterogeneous disorder, it is a highly genetic condition for which genetic testing is routinely performed. Microarray analysis is currently the standard of care genetic test for ASD, however whole genome sequencing offers several key advantages and will likely replace microarrays as a frontline genetic test in the near future. The 2nd Consultation on Translation of Genomic Advances into Health Applications took place in the spring of 2014 to broadly explore the current and potential impacts of genomic advances in supporting personalized and family-centered care for autism and related developmental conditions. In anticipation of WGS becoming a standard of care test, we examine the policy landscape and highlight the lack of consistency among guidelines regarding what genomic information should be returned to patients and their families. We also discuss the need to create the infrastructure to share clinical WGS data with researchers in a systematic and ethically defensible manner. PMID- 27274748 TI - The Developmental Expressions of Behavioural Dysregulation in a 25-Month old Infant Presenting with Sleep Problems: The Case of Emily. PMID- 27274746 TI - Characteristics of Youth Presenting to a Canadian Youth Concurrent Disorders Program: Clinical Complexity, Trauma, Adaptive Functioning and Treatment Priorities. AB - OBJECTIVE: This study describes clinical characteristics of youth presenting for service at a Canadian youth concurrent mental health and substance use disorders (SUD) program. METHOD: Participants were 100 adolescents and emerging adults (aged 14-25) who attended a Canadian concurrent mental health and substance use disorders outpatient program. SUDs were assigned using the Structured Clinical Interview for DSM-IV. Self-reported mental health symptoms, trauma exposure and adaptive functioning were also assessed. RESULTS: Eighty-three percent of participants scored over the clinical cut-off on at least one mental health scale and 33% reported at least one suicide attempt. Sixty-six percent met criteria for a current SUD; 96% met lifetime criteria. Exposure to adverse events was nearly universal (94%). Almost half of female (46%) and almost a third of male (31%) participants endorsed symptoms consistent with posttraumatic stress disorder (PTSD). Youth reported impairment and need for support in multiple domains of functioning, including school, peer, family and mental health. Substance use was least likely to be identified as a treatment priority. CONCLUSIONS: High rates of adverse events and PTSD highlight the need for trauma-informed care when providing services to this vulnerable population. Functional impairment in domains related to developmental transitions and tasks underscores the need for a developmental lens and integrated treatment that goes beyond mental health and SUD symptoms and addresses developmentally relevant domains during this transitional age. PMID- 27274749 TI - Psychotic Symptoms in a Child with Long Standing SLE Nephritis: Neuropsychiatric Manifestation or Sequelae to Lupus? AB - Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease of unknown etiology, which affects multiple organ systems including the central nervous system (CNS). Though not common, childhood onset SLE is a known and established entity. Neuropsychiatric symptoms are common in childhood onset SLE. Of these, psychosis and behavioural symptoms are relatively rare, and there is no consensus on the proper treatment of such cases. We report a case of 13-year-old boy, diagnosed with lupus nephritis, and presented with psychosis and behavioural symptoms. The highlight of this case is that the psychiatric symptoms were present despite the primary illness being quiescent. Thus, the patient was treated with Olanzapine and lorazepam, while continuing immunosuppressive therapy as previously. Also, MRI brain revealed vasculitic changes in the right hemisphere, which might be one of the etiological factors playing role in the development of these neuropsychiatric symptoms. PMID- 27274751 TI - Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model. AB - Tanshinone IIA sodium sulfonate (TSS) is a water-soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI) in D galactosamine- (D-Gal-) induced acute liver injury (ALI) in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI. PMID- 27274752 TI - Synergism Effect of the Essential Oil from Ocimum basilicum var. Maria Bonita and Its Major Components with Fluconazole and Its Influence on Ergosterol Biosynthesis. AB - The aim of this study was to evaluate the activity of the EO and its major components of Ocimum basilicum var. Maria Bonita, a genetically improved cultivar, against the fluconazole sensitive and resistant strains of Candida albicans and Cryptococcus neoformans. Geraniol presented better results than the EO, with a low MIC (76 MUg/mL against C. neoformans and 152 MUg/mL against both Candida strains). The combination of EO, linalool, or geraniol with fluconazole enhanced their antifungal activity, especially against the resistant strain (MIC reduced to 156, 197, and 38 MUg/mL, resp.). The ergosterol assay showed that subinhibitory concentrations of the substances were able to reduce the amount of sterol extracted. The substances tested were able to reduce the capsule size which suggests they have an important mechanism of action. Transmission electron microscopy demonstrated cell wall destruction of C. neoformans after treatment with subinhibitory concentrations. In C. albicans ultrastructure alterations such as irregularities in the membrane, presence of vesicles, and cell wall thickening were observed. The biofilm formation was inhibited in both C. albicans strains at MIC and twice MIC. These results provide further support for the use of O. basilicum EO and its major components as a potential source of antifungal agents. PMID- 27274753 TI - Efficacy of Oral Ginger (Zingiber officinale) for Dysmenorrhea: A Systematic Review and Meta-Analysis. AB - This systematic review examines the efficacy of oral ginger for dysmenorrhea. Key biomedical databases and grey literature were searched. We included randomized controlled trials comparing oral ginger against placebo or active treatment in women with dysmenorrhea. Six trials were identified. Two authors independently reviewed the articles, extracted data, and assessed risk of bias. Discrepancies were resolved by consensus with a third reviewer. We completed a narrative synthesis of all six studies and exploratory meta-analyses of three studies comparing ginger with placebo and two studies comparing ginger with a nonsteroidal anti-inflammatory drug (NSAID). Ginger appeared more effective for reducing pain severity than placebo. The weighted mean difference on a 10 cm visual analogue scale was 1.55 cm (favoring ginger) (95% CI 0.68 to 2.43). No significant difference was found between ginger and mefenamic acid (an NSAID). The standardized mean difference was 0 (95% CI -0.40 to 0.41). Available data suggest that oral ginger could be an effective treatment for menstrual pain in dysmenorrhea. Findings, however, need to be interpreted with caution because of the small number of studies, poor methodological quality of the studies, and high heterogeneity across trials. The review highlights the need for future trials with high methodological quality. PMID- 27274754 TI - Effect of Electroacupuncture on the Expression of Glycyl-tRNA Synthetase and Ultrastructure Changes in Atrophied Rat Peroneus Longus Muscle Induced by Sciatic Nerve Injection Injury. AB - Glycyl-tRNA synthetase (GlyRS) is one of the key enzymes involved in protein synthesis. Its mutations have been reported to cause Charcot-Marie-Tooth disease which demonstrates muscular atrophy in distal extremities, particularly manifested in peroneus muscles. In this situation, the dysfunctions of mitochondria and sarcoplasmic reticulum (SR) affect energy supply and excitation contraction coupling of muscle fibers, therefore resulting in muscular atrophy. Although the treatment of muscular atrophy is a global urgent problem, it can be improved by electroacupuncture (EA) treatment. To investigate the mechanism underlying EA treatment improving muscular atrophy, we focused on the perspective of protein synthesis by establishing a penicillin injection-induced sciatic nerve injury model. In our model, injured rats without treatment showed decreased sciatic functional index (SFI), decreased peroneus longus muscle weight and muscle fiber cross-sectional area, aggregated mitochondria with vacuoles appearing, swollen SR, and downregulated mRNA and protein expression levels of GlyRS and myosin heavy chain IIb (MHC-IIb). The injured rats with EA treatment showed significant recovery. These results indicated that EA stimulation can alleviate peroneus longus muscular atrophy induced by iatrogenic sciatic nerve injury through promoting the recovery of GlyRS and muscle ultrastructure and increasing muscle protein synthesis. PMID- 27274755 TI - Chinese Medicinal Leech: Ethnopharmacology, Phytochemistry, and Pharmacological Activities. AB - Hirudo (Shuizhi in Chinese) is an important Chinese medicine, which possesses many therapeutic properties for the treatment of the cerebral hemorrhage and other thrombosis-related diseases. The phytochemical investigation gave more than 51 compounds including pteridines, phosphatidylcholines, glycosphingolipids, and sterols, as well as some bioactive peptides from the Shuizhi derived from three animal species recorded in the current Chinese Pharmacopoeia. The pharmacological studies on the Shuizhi have revealed various activities such as anticoagulation, antithrombosis, antiatherosclerosis, antiplatelet aggregation, antitumor and anti inflammatory as well as hemorheology improvement, and protective effects against cerebral ischemia-reperfusion injury. However, some important issues based on the traditional uses of Shuizhi are still not clear. The aim of the present review is to provide comprehensive knowledge on the ethnopharmacology, phytochemistry, and pharmacological activities of Shuizhi. It will provide a potential guidance in exploring main active compounds of Shuizhi and interpreting the action mechanism for the further research. PMID- 27274756 TI - Immune Signatures in Patients with Psoriasis Vulgaris of Blood-Heat Syndrome: A Systematic Review and Meta-Analysis. AB - Objective. To determine whether immunological serum markers IFN-gamma, IL-4, IL 17, IL-23, IL-6, TNF-alpha, and IL-10 are elevated or decreased in patients compared with healthy controls. Methods. A complete search of the literature on this topic within the past 30 years was conducted across seven databases. Seventeen studies including 768 individuals were identified. Differences in serum marker levels between subjects and controls were pooled as MDs using the random effects model. Results. The pooled MDs were higher in patients than in healthy controls for IFN-gamma (MD 24.9, 95% CI 12.36-37.43), IL-17 (MD 28.92, 95% CI 17.44-40.40), IL-23 (MD 310.60, 95% CI 4.96-616.24), and TNF-alpha (MD 19.84, 95% CI 13.80-25.87). Pooled IL-4 (MD -13.5, 95% CI -17.74--9.26) and IL-10 (MD 10.33, 95% CI -12.03--8.63) levels were lower in patients. Conclusion. The pooled analyses suggest that levels of IFN-gamma, IL-17, IL-23, and TNF-alpha are significantly elevated and that levels of IL-4 and IL-10 are significantly decreased in sera of patients with psoriasis vulgaris of blood-heat syndrome. Measuring progression of blood-heat syndrome of psoriasis vulgaris will require additional high-quality data, with a low risk of bias and adequate sample sizes, before and after antipsoriatic therapy. PMID- 27274757 TI - Elevational spatial compounding for enhancing image quality in echocardiography. AB - INTRODUCTION: Echocardiography is commonly used in clinical practice for the real time assessment of cardiac morphology and function. Nevertheless, due to the nature of the data acquisition, cardiac ultrasound images are often corrupted by a range of acoustic artefacts, including acoustic noise, speckle and shadowing. Spatial compounding techniques have long been recognised for their ability to suppress common ultrasound artefacts, enhancing the imaged cardiac structures. However, they require extended acquisition times as well as accurate spatio temporal alignment of the compounded data. Elevational spatial compounding acquires and compounds adjacent partially decorrelated planes of the same cardiac structure. METHODS: This paper employs an anthropomorphic left ventricle phantom to examine the effect of acquisition parameters, such as inter-slice angular displacement and 3D sector angular range, on the elevational spatial compounding of cardiac ultrasound data. RESULTS AND CONCLUSION: Elevational spatial compounding can produce substantial noise and speckle suppression as well as visual enhancement of tissue structures even for small acquisition sector widths (2.5 degrees to 6.5 degrees ). In addition, elevational spatial compounding eliminates the need for extended acquisition times as well as the need for temporal alignment of the compounded datasets. However, moderate spatial registration may still be required to reduce any tissue/chamber blurring side effects that may be introduced. PMID- 27274758 TI - Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study. AB - BACKGROUND: In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly. RESULTS: IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n = 3496 individuals, p < 0.001 and CRP: n = 3632, p = 0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score >=24 and a Katz Activities of Daily Living (ADL) score >=5 (IL-6: n = 1258, p < 0.001 and CRP: n = 1312, p < 0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n = 2238, p < 0.001 and CRP: n = 2320, p = 0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p < 0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p < 0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR = 1.063 per each pg/mL, 95 % CI: 1.052-1.074, p < 0.001 and HR = 1.020 per each mg/L, 95 % CI: 1.015 1.025, p < 0.001, respectively) but also in the successfully aging subgroup (HR = 1.163 per each pg/mL, 95 % CI: 1.128-1.199, p < 0.001 and HR = 1.074 per each mg/L, 95 % CI: 1.047-1.100, p < 0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p < 0.001). CONCLUSIONS: Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals. PMID- 27274759 TI - Interaction between FTO gene variants and lifestyle factors on metabolic traits in an Asian Indian population. AB - BACKGROUND: Lifestyle factors such as diet and physical activity have been shown to modify the association between fat mass and obesity-associated (FTO) gene variants and metabolic traits in several populations; however, there are no gene lifestyle interaction studies, to date, among Asian Indians living in India. In this study, we examined whether dietary factors and physical activity modified the association between two FTO single nucleotide polymorphisms (rs8050136 and rs11076023) (SNPs) and obesity traits and type 2 diabetes (T2D). METHODS: The study included 734 unrelated T2D and 884 normal glucose-tolerant (NGT) participants randomly selected from the urban component of the Chennai Urban Rural Epidemiology Study (CURES). Dietary intakes were assessed using a validated interviewer administered semi-quantitative food frequency questionnaire (FFQ). Physical activity was based upon the self-report. Interaction analyses were performed by including the interaction terms in the linear/logistic regression model. RESULTS: There was a significant interaction between SNP rs8050136 and carbohydrate intake (% energy) (Pinteraction = 0.04), where the 'A' allele carriers had 2.46 times increased risk of obesity than those with 'CC' genotype (P = 3.0 * 10(-5)) among individuals in the highest tertile of carbohydrate intake (% energy, 71 %). A significant interaction was also observed between SNP rs11076023 and dietary fibre intake (Pinteraction = 0.0008), where individuals with AA genotype who are in the 3(rd) tertile of dietary fibre intake had 1.62 cm lower waist circumference than those with 'T' allele carriers (P = 0.02). Furthermore, among those who were physically inactive, the 'A' allele carriers of the SNP rs8050136 had 1.89 times increased risk of obesity than those with 'CC' genotype (P = 4.0 * 10(-5)). CONCLUSIONS: This is the first study to provide evidence for a gene-diet and gene-physical activity interaction on obesity and T2D in an Asian Indian population. Our findings suggest that the association between FTO SNPs and obesity might be influenced by carbohydrate and dietary fibre intake and physical inactivity. Further understanding of how FTO gene influences obesity and T2D through dietary and exercise interventions is warranted to advance the development of behavioral intervention and personalised lifestyle strategies, which could reduce the risk of metabolic diseases in this Asian Indian population. PMID- 27274760 TI - Association of low oleic acid intake with diabetic retinopathy in type 2 diabetic patients: a case-control study. AB - BACKGROUND: The objective of this study was to describe the intake of macronutrient, especially fatty acids, and explore their possible effect on diabetic retinopathy (DR) in patients with type 2 diabetes mellitus. METHODS: In this case-control study, we included a total of 146 patients with DR and 148 without DR. The intake of macronutrient was evaluated using a validated food frequency questionnaire. We used logistic regression adjusted for sex, age, diabetes duration, energy intake, educational level, physical activity, waist circumference, systolic blood pressure, high-density lipoprotein cholesterol and diabetes treatment, to estimate odds ratio (ORs) of DR. RESULTS: Patients with DR had significantly lower intake of fibre, monounsaturated fatty acids (MUFA), and palmitic and oleic acid. Inverse associations were observed between MUFA and oleic acid intake in DR. Subjects with intermediate and high MUFA intake were less likely to have DR than those with lower MUFA intake, with ORs of 0.46 (95 % CI: 0.22-0.93) and 0.42 (95 % CI: 0.18-0.97), respectively. Similarly, intermediate and high oleic acid intake were associated with reduced DR frequency compared with low oleic acid intake, with OR values of 0.48 (95 % CI: 0.23-0.97) and 0.37 (95 % CI: 0.16-0.85), respectively. These associations were stronger in patients with a longer diabetes duration. CONCLUSION: In type 2 diabetes mellitus, MUFA and oleic acid intake were inversely associated with DR. PMID- 27274761 TI - Towards integrated care in breastfeeding support: a cross-sectional survey of practitioners' perspectives. AB - BACKGROUND: Integrated care is defined as concerted action of healthcare providers ensuring continuity of care within a patient-centered approach, thus contributing to healthcare efficiency and quality. Apart from the WHO/UNICEF Baby Friendly Initiatives, integrated care has been poorly explored within the context of breastfeeding support. The aim of this study was to investigate the experience of breastfeeding support practitioners, identifying barriers and facilitators towards integrated care. METHODS: A 62-item survey was conducted among 900 participants at 3 international breastfeeding conferences. Analysis included uni and bivariate descriptive statistics, categorizing of mutually exclusive response groups and thematic networks analysis of responses to 18 open-ended items. RESULTS: Three-hundred-and-one participants (33 % response), from 34 predominantly industrialized countries (98 %) on nearly all continents, responded to the survey. Norwegian residents alone, felt sufficiently supported in providing breastfeeding support by other healthcare providers, the work environment, society, the media and their National Breastfeeding Committee (P < 0.05). Out of 11 suggested measures for effective breastfeeding promotion, 96 % of respondents ranked integrated care as the most important. The largest response group identified in open-ended items, as a major barrier to integrated care in breastfeeding support, was "lacking or failing health promotion strategies" (n = 454), followed by "a lack of vertically integrated care" (n =268), described mainly as unsatisfactory cooperation within healthcare. This inconsistency of care also impairs "shared decision-making" on infant feeding for parents, including accessibility of information and support (n = 265). Among other measures, 29 % of respondents recommended incentivizing integrated breastfeeding support within healthcare. Two figures, based on open-ended response evaluations, illustrate participants' ideas of the National Breastfeeding Committees' role in coordinating policies and protagonists towards integrated breastfeeding support, and a family-centered model of integrated care to facilitate successful breastfeeding. CONCLUSIONS: According to practitioners in breastfeeding support, integrated care is essential for successful breastfeeding. Quality and accessibility of breastfeeding support should be motivated by healthcare system incentives, to counter the reported lack of consistency of care within and beyond healthcare. To effectively integrate a continuum of breastfeeding support into healthcare and society, a policy consensus and strong political action are indispensable, with coordination by an empowered National Breastfeeding Committee. PMID- 27274762 TI - A Mathematical Model of Regenerative Axon Growing along Glial Scar after Spinal Cord Injury. AB - A major factor in the failure of central nervous system (CNS) axon regeneration is the formation of glial scar after the injury of CNS. Glial scar generates a dense barrier which the regenerative axons cannot easily pass through or by. In this paper, a mathematical model was established to explore how the regenerative axons grow along the surface of glial scar or bypass the glial scar. This mathematical model was constructed based on the spinal cord injury (SCI) repair experiments by transplanting Schwann cells as bridge over the glial scar. The Lattice Boltzmann Method (LBM) was used in this model for three-dimensional numerical simulation. The advantage of this model is that it provides a parallel and easily implemented algorithm and has the capability of handling complicated boundaries. Using the simulated data, two significant conclusions were made in this study: (1) the levels of inhibitory factors on the surface of the glial scar are the main factors affecting axon elongation and (2) when the inhibitory factor levels on the surface of the glial scar remain constant, the longitudinal size of the glial scar has greater influence on the average rate of axon growth than the transverse size. These results will provide theoretical guidance and reference for researchers to design efficient experiments. PMID- 27274763 TI - A Time-Delayed Mathematical Model for Tumor Growth with the Effect of a Periodic Therapy. AB - A time-delayed mathematical model for tumor growth with the effect of periodic therapy is studied. The establishment of the model is based on the reaction diffusion dynamics and mass conservation law and is considered with a time delay in cell proliferation process. Sufficient conditions for the global stability of tumor free equilibrium are given. We also prove that if external concentration of nutrients is large the tumor will not disappear and the conditions under which there exist periodic solutions to the model are also determined. Results are illustrated by computer simulations. PMID- 27274764 TI - The Numerical Study of the Hemodynamic Characteristics in the Patient-Specific Intracranial Aneurysms before and after Surgery. AB - The patient-specific pre- and postsurgery cerebral arterial geometries in the study were reconstructed from computed tomography angiography (CTA). Three dimensional computational fluid dynamics models were used to investigate the hemodynamic phenomena in the cerebral arteries before and after surgery of the aneurysm under realistic conditions. CFD simulations for laminar flow of incompressible Newtonian fluid were conducted by using commercial software, ANSYS v15, with the rigid vascular wall assumption. The study found that the flow patterns with the complex vortical structures inside the aneurysm were similar. We also found that the inflow jet streams were coming strongly in aneurysm sac in the presurgery models, while the flow patterns in postsurgery models were quite different from those in presurgery models. The average wall shear stress after surgery for model 1 was approximately three times greater than that before surgery, while it was about twenty times greater for model 2. The area of low WSS in the daughter saccular aneurysm region in model 2 is associated with aneurysm rupture. Thus the distribution of WSS in aneurysm region provides useful prediction for the risk of aneurysm rupture. PMID- 27274765 TI - Abdominal bloating is the most bothersome symptom in irritable bowel syndrome with constipation (IBS-C): a large population-based Internet survey in Japan. AB - BACKGROUND: Abdominal bloating is a common symptom in patients with irritable bowel syndrome with constipation (IBS-C). However, it is not included among the required items in the Rome III diagnostic criteria for IBS. Little is known about an impact of abdominal bloating seen in patients with IBS-C. Using a large population-based sample, the aim of the present study was to investigate what is the most bothersome symptom in subjects with IBS-C. METHODS: An Internet survey of 30,000 adults drawn from the general public throughout Japan was conducted to identify subtypes of IBS using the Rome III diagnostic questionnaire. Consecutively, the screened subjects with IBS-C and the same number of age- and sex-matched non-IBS subjects who were randomly selected as controls were asked to answer a questionnaire on the degree of anxiety they experienced in their daily lives, thoughts about bowel habit, and their dominant gastrointestinal symptoms together with exacerbation factors (for IBS-C only). RESULTS: The screening survey showed that the prevalence of overall IBS was 16.5 % (female 17.4 %, male 15.5 %) and that 2.8 % met the criteria for IBS-C, 4.5 % for IBS with diarrhea (IBS-D) and 8.2 % for mixed IBS (IBS-M). Seven hundred and fifty-nine of 835 (90.9 %) subjects with IBS-C and 746 of 830 (89.9 %) control subjects completed the consecutive questionnaire. IBS-C subjects felt a higher degree of anxiety in their daily lives (p < 0.01) and considered bowel habit to be an indicator of health (p < 0.01) to a greater extent than control subjects. In IBS-C, the degree of anxiety was significantly associated with abdominal discomfort (p < 0.01), pain (p < 0.01) and bloating (p = 0.02), but not with the frequency of bowel habit (p > 0.1). Abdominal bloating was the most bothersome symptom (27.5 %), which was more likely to occur after a meal (52.2 %), at work/school (29.2 %) and during times of stress (26.8 %). Only 4.5 % of IBS-C subjects reported abdominal pain as the 'most bothersome' symptom. CONCLUSIONS: A large population-based Internet survey suggests that abdominal bloating has a great impact on the daily lives of subjects diagnosed with IBS-C. Not only bowel movement/abdominal pain but also abdominal bloating should be evaluated in patients with IBS-C. PMID- 27274767 TI - A survey on patients' knowledge and expectations during informed consent for spinal surgery: can we improve the shared decision-making process? AB - BACKGROUND: The informed medical consent in surgery requires to some point basic medical knowledge. The treating physicians while explaining the details and risks of the recommended procedure often imply this. We hypothesized, that patients do not have adequate medical understanding to decide about the ongoing therapy and its potential complications based on knowledge jeopardizing the patients' safety. METHODS: We conducted a retrospective analysis of a prospective database using a multiple choice questionnaire with 10 basic questions about anatomy, clinical symptoms and therapies of spinal diseases in our spine clinic at a German university hospital. Included were all patients at the spine clinic who agreed to the study and to fill in the questionnaire. Furthermore the patients age, mother tongue, the past spinal surgical history, the length of duration of symptoms and the patients education were inquired. The data were analyzed descriptive. RESULTS: Included were 248 patients with an average age of 59 years (16-88 a). 70 % of all patients used German as their mother tongue. 30 % of the included patients already had spinal surgery and suffered on average for 13.4 years because of their spinal disorder. Overall 32.6 % of all questions were answered correctly (range 0.8-68 %). A correlation of correctly answered questions and the patients' age, duration of symptoms, mother tongue, education and past surgical history could not be described. CONCLUSION: The percentage of correctly answered questions is almost as low as the likelihood of nearness in guessing. Having this in mind the patients do not choose any treatment option based on knowledge. The physicians need to provide more basic knowledge to the patients. This would increase the amount of successful therapies, content patients and the patients safety. PMID- 27274766 TI - Adsorption and mechanism of cellulase enzymes onto lignin isolated from corn stover pretreated with liquid hot water. AB - BACKGROUND: In the bioconversion of lignocellulosic substrates, the adsorption behavior of cellulase onto lignin has a negative effect on enzymatic hydrolysis of cellulose, decreasing glucose production during enzymatic hydrolysis, thus decreasing the yield of fermentation and the production of useful products. Understanding the interaction between lignin and cellulase is necessary to optimize the components of cellulase mixture, genetically engineer high efficiency cellulase, and reduce cost of bioconversion. Most lignin is not removed during liquid hot water (LHW) pretreatment, and the characteristics of lignin in solid substrate are also changed. To understand the interactions between cellulase and lignin, this study investigated the change in the characteristics of lignin obtained from corn stover, as well as the behavior of cellulase adsorption onto lignin, under various severities of LHW pretreatment. RESULTS: LHW pretreatment removed most hemicellulose and some lignin in corn stover, as well as improved enzymatic digestibility of corn stover. After LHW pretreatment, the molecular weight of lignin obviously increased, whereas its polydispersity decreased and became more negative. The hydrophobicity and functional groups in lignin also changed. Adsorption of cellulase from Penicillium oxalicum onto lignin isolated from corn stover was enhanced after LHW pretreatment, and increased under increasing pretreatment severity. Different adsorption behaviors were observed in different lignin samples and components of cellulase mixtures, even in different cellobiohydrolases (CBHs), endo-beta-1, 4 glucanases (EGs). The greatest reduction in enzyme activity caused by lignin was observed in CBH, followed by that in xylanase and then in EG and beta-Glucosidase (BGL). The adsorption behavior exerted different effects on subsequent enzymatic hydrolysis of various biomass substrates. Hydrophobic and electrostatic interactions may be important factors affecting different adsorption behaviors between lignin and cellulase. CONCLUSIONS: LHW pretreatment changed the characteristics of the remaining lignin in corn stover, thus affected the adsorption behavior of lignin toward cellulase. For different protein components in cellulase solution from P. oxalicum, electrostatic action was a main factor influencing the adsorption of EG and xylanase onto lignin in corn stover, while hydrophobicity affected the adsorption of CBH and BGL onto lignin. PMID- 27274768 TI - Protective role for miR-9-5p in the fibrogenic transformation of human dermal fibroblasts. AB - BACKGROUND: Excessive accumulation of extracellular matrix (ECM) proteins is the hallmark of fibrotic diseases, including skin fibrosis. This response relies on the activation of dermal fibroblasts that evolve into a pro-fibrogenic phenotype. One of the major players in this process is the cytokine transforming growth factor-beta (TGF-beta). MicroRNAs (miRNAs) are small non-coding RNAs that post transcriptionally regulate gene expression affecting a wide range of pathophysiological events including fibrogenesis. MicroRNA-9-5p (miR-9-5p) has been shown to exert a protective role in lung and peritoneal fibrosis. This study aimed to evaluate the role of miR-9-5p in skin fibrosis. RESULTS: miR-9-5p is up regulated in TGF-beta1-treated human dermal fibroblasts (HDFs). In silico identification of miR-9-5p targets spotted the type II TGF-beta receptor (TGFBR2) as a potential TGF-beta signaling-related effector for this miRNA. Consistently, over-expression of miR-9-5p in HDFs down-regulated TGFBR2 at both the mRNA and protein levels and reduced the phosphorylation of Smad2 and the translocation of Smad2/3 to the nucleus. In keeping, over-expression of miR-9-5p significantly delayed TGF-beta1-dependent transformation of dermal fibroblasts, decreasing the expression of ECM protein collagen, type I, alpha 1 (Col1alpha1), and fibronectin (FN), the amount of secreted collagen proteins, and the expression of the archetypal myofibroblast marker alpha-smooth muscle actin (alpha-SMA). By contrast, specific inhibition of miR-9-5p resulted in enhanced presence of fibrosis markers. The expression of miR-9-5p was also detected in the skin and plasma in the mouse model of bleomycin-induced dermal fibrosis. Using lentiviral constructs, we demonstrated that miR-9-5p over-expression was also capable of deterring fibrogenesis in this same model. CONCLUSIONS: miR-9-5p significantly prevents fibrogenesis in skin fibrosis. This is mediated by an abrogation of TGF beta-mediated signaling through the down-regulation of TGFBR2 expression in HDFs. These results may pave the way for future diagnostic or therapeutic developments for skin fibrosis based on miR-9-5p. PMID- 27274770 TI - Are the physicochemical properties of antibacterial compounds really different from other drugs? AB - BACKGROUND: It is now widely recognized that there is an urgent need for new antibacterial drugs, with novel mechanisms of action, to combat the rise of multi drug resistant bacteria. However, few new compounds are reaching the market. Antibacterial drug discovery projects often succeed in identifying potent molecules in biochemical assays but have been beset by difficulties in obtaining antibacterial activity. A commonly held view, based on analysis of marketed antibacterial compounds, is that antibacterial drugs possess very different physicochemical properties to other drugs, and that this profile is required for antibacterial activity. RESULTS: We have re-examined this issue by performing a cheminformatics analysis of the literature data available in the ChEMBL database. The physicochemical properties of compounds with a recorded activity in an antibacterial assay were calculated and compared to two other datasets extracted from ChEMBL, marketed antibacterials and drugs marketed for other therapeutic indications. The chemical class of the compounds and Gram-negative/Gram-positive profile were also investigated. This analysis shows that compounds with antibacterial activity have physicochemical property profiles very similar to other drug classes. CONCLUSIONS: The observation that many current antibacterial drugs lie in regions of physicochemical property space far from conventional small molecule therapeutics is correct. However, the inference that a compound must lie in one of these "outlier" regions in order to possess antibacterial activity is not supported by our analysis. Graphical abstract. PMID- 27274769 TI - Interstitial 6q21q23 duplication - variant of variable phenotype and incomplete penetrance or benign duplication? AB - BACKGROUND: Chromosome 6q duplication syndrome is a chromosome abnormality associated with characteristic phenotypic features such as intellectual disability (ID), short stature, feeding difficulties, microcephaly, dysmorphic features (prominent forehead, downslanting palpebral fissures, flat nasal bridge, tented upper lip, micrognathia, short webbed neck) and joint contractures. Only a few cases of pure partial 6q trisomy have been published and the severity of the phenotype seems to depend on the breakpoint position. Unfortunately, most of these cases were identified using karyotyping or FISH, so breakpoints at the molecular level and thus gene content are not known. CASES PRESENTATION: We report the first two families with an interstitial 6q duplication identified by karyotyping where the gene content and breakpoints were characterized with microarray. In family 1, the 6q22.1q23.2 duplication was detected in a female patient with ID. In family 2, the 6q21q22.33 duplication was identified in a male fetus with multiple congenital malformations. In both families, the duplication seems to show phenotypic heterogeneity and in family 1 also incomplete penetrance suggesting the co-existence of an "additional hit" in affected patients. This "additional hit" was identified in the first family to be a microduplication in 16p11.2, a known susceptibility locus (SL) for neurodevelopmental disorders, that co-segregated with an abnormal phenotype in the affected family members. CONCLUSIONS: Our study shows that interstitial 6q21q23 duplication may represent a private variant that is benign, but may also contribute to developmental disorders of variable expressivity in a "multi-hit" model. Finding the "additional hit" within the family is therefore very important for genetic counseling and assessment of the CNV penetrance within the particular family. PMID- 27274771 TI - Calcific Aortic Valve Disease: Molecular Mechanisms and Therapeutic Approaches. AB - Calcification occurs in atherosclerotic vascular lesions and In the aortic valve. Calcific aortic valve disease (CAVD) is a slow, progressive disorder that ranges from mild valve thickening without obstruction of blood flow, termed aortic sclerosis, to severe calcification with impaired leaflet motion, termed aortic stenosis. In the past, this process was thought to be 'degenerative' because of time-dependent wear and tear of the leaflets, with passive calcium deposition. The presence of osteoblasts in atherosclerotic vascular lesions and in CAVD implies that calcification is an active, regulated process akin to atherosclerosis, with lipoprotein deposition and chronic inflammation. If calcification is active, via pro-osteogenic pathways, one might expect that development and progression of calcification could be inhibited. The overlap in the clinical factors associated with calcific valve disease and atherosclerosis provides further support for a shared disease mechanism. In our recent research we used an in vitro porcine valve interstitial cell model to study spontaneous calcification and potential promoters and inhibitors. Using this model, we found that denosumab, a human monoclonal antibody targeting the receptor activator of nuclear factor-kappaB ligand may, at a working concentration of 50 MUg/mL, inhibit induced calcium deposition to basal levels. PMID- 27274772 TI - LEADER 7: cardiovascular risk profiles of US and European participants in the LEADER diabetes trial differ. AB - AIMS: To determine whether US and European participants in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial differ regarding risk factors for cardiovascular mortality and morbidity. METHODS: Baseline data, stratified for prior cardiovascular disease (CVD), were compared using multivariable logistic regression analysis to establish whether region is an independent determinant of achieved targets for glycated hemoglobin (HbA1c), blood pressure (BP), and low-density lipoprotein (LDL)-cholesterol. RESULTS: Independent of CVD history, US participants were more often of non-White origin and had a longer history of type 2 diabetes, higher body weight, and higher baseline HbA1c. They had substantially lower systolic and diastolic BP, and a marginally lower LDL-cholesterol level. Fewer US participants were diagnosed with left ventricular dysfunction. In the largest group of patients, those with prior CVD and the highest cardiovascular risk, US participants were more often female, had a higher waist circumference, and had a decreased estimated glomerular filtration rate, but less frequently prior myocardial infarction or angina pectoris. CONCLUSIONS: There were baseline differences between US and European participants. These differences may result from variation in regional targets for cardiovascular risk factor management, and should be considered in the analysis and reporting of the trial results. Clinical trial identifier: ClinicalTrials.gov, NCT01179048. PMID- 27274773 TI - Introducing the American Heritage Time Use Study Data Extract Builder (AHTUS-X). PMID- 27274774 TI - Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. AB - BACKGROUND: Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand such observations by investigating whether different concepts of the epigenetic clocks in a population-based cohort are associated with cancer, cardiovascular, and all-cause mortality. RESULTS: DNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Deltaage) was calculated. A case-cohort design and weighted proportional Cox hazard models were used to estimate associations of Deltaage with cancer, cardiovascular, and all-cause mortality. Hazard ratios for Deltaage (per 5 years) calculated using the epigenetic clock developed by Horvath were 1.23 (95 % CI 1.10-1.38) for all-cause mortality, 1.22 (95 % CI 1.03-1.45) for cancer mortality, and 1.19 (95 % CI 0.98-1.43) for cardiovascular mortality after adjustment for batch effects, age, sex, educational level, history of chronic diseases, hypertension, smoking status, body mass index, and leucocyte distribution. Associations were similar but weaker for Deltaage calculated using the epigenetic clock developed by Hannum. CONCLUSIONS: These results show that age acceleration in terms of the difference between age predicted by DNA methylation and chronological age is an independent predictor of all-cause and cause-specific mortality and may be useful as a general marker of healthy aging. PMID- 27274775 TI - Multimorbidity in Older Patients with Cardiovascular Disease. AB - Multimorbidity affects more than two thirds of older individuals and the vast majority of patients with chronic cardiovascular disease. Patients with multimorbidity have high resource utilization, poor mobility, and poor health status and are at an increased risk for death. The presence of multimorbidity imposes numerous management challenges in caring for patients with chronic cardiovascular disease. It complicates decision-making, promotes fragmented care, and imposes an immense burden on the patient and their social support system. Novel models of care, such as the cardiovascular patient-centered medical home, are needed to provide high-quality, efficient, effective care to this growing population. PMID- 27274776 TI - Civil Society Organizations and the Functions of Global Health Governance: What Role within Intergovernmental Organizations? AB - Amid discussion of how global health governance should and could be strengthened, the potential role of civil society organizations has been frequently raised. This paper considers the role of Civil Society Organizations (CSOs) in four health governance instruments under the auspices of the World Health Organization - the International Code on the Marketing of Breastmilk Substitutes, Framework Convention on Tobacco Control, International Health Regulations and Codex Alimentarius - and maps the functions they have contributed to. The paper draws conclusions about the opportunities and limitations CSOs represent for strengthening global health governance (GHG). PMID- 27274777 TI - Protective Effects of Carvedilol and Vitamin C against Azithromycin-Induced Cardiotoxicity in Rats via Decreasing ROS, IL1-beta, and TNF-alpha Production and Inhibiting NF-kappaB and Caspase-3 Expression. AB - The Food and Drug Administration recently warned of the fatal cardiovascular risks of azithromycin in humans. In addition, a recently published study documented azithromycin-induced cardiotoxicity in rats. This study aimed to justify the exact cardiovascular events accompanying azithromycin administration in rats, focusing on electrocardiographic, biochemical, and histopathological changes. In addition, the underlying mechanisms were studied regarding reactive oxygen species production, cytokine release, and apoptotic cell-death. Finally, the supposed protective effects of both carvedilol and vitamin C were assessed. Four groups of rats were used: (1) control, (2) azithromycin, (3) azithromycin + carvedilol, and (4) azithromycin + vitamin C. Azithromycin resulted in marked atrophy of cardiac muscle fibers and electrocardiographic segment alteration. It increased the heart rate, lactate dehydrogenase, creatine phosphokinase, malondialdehyde, nitric oxide, interleukin-1 beta (IL1-beta), tumor necrosis factor alpha (TNF-alpha), nuclear factor kappa beta (NF-kappaB), and caspase-3. It decreased reduced glutathione, glutathione peroxidase, and superoxide dismutase. Carvedilol and vitamin C prevented most of the azithromycin-induced electrocardiographic and histopathological changes. Carvedilol and vitamin C decreased lactate dehydrogenase, malondialdehyde, IL1-beta, TNF-alpha, NF-kappaB, and caspase-3. Both agents increased glutathione peroxidase. This study shows that both carvedilol and vitamin C protect against azithromycin-induced cardiotoxicity through antioxidant, immunomodulatory, and antiapoptotic mechanisms. PMID- 27274778 TI - The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. AB - Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p < 0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p = 0.03). Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria targeted antioxidants as an analgesic. PMID- 27274779 TI - Association of Nuclear Factor-Erythroid 2-Related Factor 2, Thioredoxin Interacting Protein, and Heme Oxygenase-1 Gene Polymorphisms with Diabetes and Obesity in Mexican Patients. AB - The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of NAD(P)H: quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls. The results showed that the rs7211 polymorphism is a protective factor against obesity in nondiabetic subjects (CC + CT versus TT, OR = 0.40, P = 0.005) and in women (CC versus CT + TT, OR = 0.7, P = 0.016). TT carriers had lower high-density lipoprotein cholesterol levels and lower body mass index. The rs2071749 was positively associated with obesity (AA versus AG + GG, OR = 1.25, P = 0.026). Finally, the rs6721961 was negatively associated with diabetes in men (CC versus CA + AA, OR = 0.62, P = 0.003). AA carriers showed lower glucose concentrations. No association was found for rs1800566 and rs2364723 polymorphisms. In conclusion, the presence of Nrf2 and related genes polymorphisms are associated with diabetes and obesity in Mexican patients. PMID- 27274780 TI - An Evidence-Based Review of Related Metabolites and Metabolic Network Research on Cerebral Ischemia. AB - In recent years, metabolomics analyses have been widely applied to cerebral ischemia research. This paper introduces the latest proceedings of metabolomics research on cerebral ischemia. The main techniques, models, animals, and biomarkers of cerebral ischemia will be discussed. With analysis help from the MBRole website and the KEGG database, the altered metabolites in rat cerebral ischemia were used for metabolic pathway enrichment analyses. Our results identify the main metabolic pathways that are related to cerebral ischemia and further construct a metabolic network. These results will provide useful information for elucidating the pathogenesis of cerebral ischemia, as well as the discovery of cerebral ischemia biomarkers. PMID- 27274782 TI - Draft genome sequence of Fusicladium effusum, cause of pecan scab. AB - Pecan scab, caused by the plant pathogenic fungus Fusicladium effusum, is the most destructive disease of pecan, an important specialty crop cultivated in several regions of the world. Only a few members of the family Venturiaceae (in which the pathogen resides) have been reported sequenced. We report the first draft genome sequence (40.6 Mb) of an isolate F. effusum collected from a pecan tree (cv. Desirable) in central Georgia, in the US. The genome sequence described will be a useful resource for research of the biology and ecology of the pathogen, coevolution with the pecan host, characterization of genes of interest, and development of markers for studies of genetic diversity, genotyping and phylogenetic analysis. The annotation of the genome is described and a phylogenetic analysis is presented. PMID- 27274781 TI - Antidiabetic and Antinephritic Activities of Aqueous Extract of Cordyceps militaris Fruit Body in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats. AB - Cordyceps militaris has long been used as a crude drug and folk tonic food in East Asia. The present study aims to evaluate the antidiabetic and antinephritic effects of the aqueous extract of the Cordyceps militaris fruit body (CM) in diet streptozotocin- (STZ-) induced diabetic rats. During four weeks of continuous oral administration of CM at doses of 0.5, 1.0, and 2.0 g/kg and metformin at 100 mg/kg, the fasting blood glucose and bodyweight of each rat were monitored. Hypoglycemic effects of CM on diabetic rats were indicated by decreases in plasma glucose, food and water intake, and urine output. The hypolipidemic activity of CM was confirmed by the normalization of total cholesterol, triglycerides, and low- and high-density lipoprotein cholesterol in diabetic rats. Inhibitory effects on albuminuria, creatinine, urea nitrogen, and n-acetyl-beta-d glucosaminidase verified CM's renal protective activity in diabetic rats. Furthermore, CM exerted beneficial modulation of inflammatory factors and oxidative enzymes. Compared with untreated diabetic rats, CM decreased the expression of phosphor-AKT and phosphor-GSK-3beta in the kidneys. Altogether, via attenuating oxidative stress, CM displayed antidiabetic and antinephritic activities in diet-STZ-induced diabetic rats. PMID- 27274783 TI - Comparing polysaccharide decomposition between the type strains Gramella echinicola KMM 6050(T) (DSM 19838(T)) and Gramella portivictoriae UST040801 001(T) (DSM 23547(T)), and emended description of Gramella echinicola Nedashkovskaya et al. 2005 emend. Shahina et al. 2014 and Gramella portivictoriae Lau et al. 2005. AB - Strains of the genus Gramella (family Flavobacteriacae, phylum Bacteroidetes) were isolated from marine habitats such as tidal flat sediments, coastal surface seawater and sea urchins. Flavobacteriaceae have been shown to be involved in the decomposition of plant and algal polysaccharides. However, the potential to decompose polysaccharides may differ tremendously even between species of the same genus. Gramella echinicola KMM 6050(T) (DSM 19838(T)) and Gramella portivictoriae UST040801-001(T) (DSM 23547(T)) have genomes of similar lengths, similar numbers of protein coding genes and RNA genes. Both genomes encode for a greater number of peptidases compared to 'G. forsetii'. In contrast to the genome of 'G. forsetii', both genomes comprised a smaller set of CAZymes. Seven polysaccharide utilization loci were identified in the genomes of DSM 19838(T) and DSM 23547(T). Both Gramella strains hydrolyzed starch, galactomannan, arabinoxylan and hydroxyethyl-cellulose, but not pectin, chitosan and cellulose (Avicel). Galactan and xylan were hydrolyzed by strain DSM 19838(T), whereas strain DSM 23547(T) hydrolyzed pachyman and carboxy-methyl cellulose. Conclusively, both Gramella type strains exhibit characteristic physiological, morphological and genomic differences that might be linked to their habitat. Furthermore, the identified enzymes mediating polysaccharide decomposition, are of biotechnological interest. PMID- 27274784 TI - Complete genome sequence of the haloalkaliphilic, obligately chemolithoautotrophic thiosulfate and sulfide-oxidizing gamma-proteobacterium Thioalkalimicrobium cyclicum type strain ALM 1 (DSM 14477(T)). AB - Thioalkalimicrobium cyclicum Sorokin et al. 2002 is a member of the family Piscirickettsiaceae in the order Thiotrichales. The gamma-proteobacterium belongs to the colourless sulfur-oxidizing bacteria isolated from saline soda lakes with stable alkaline pH, such as Lake Mono (California) and Soap Lake (Washington State). Strain ALM 1(T) is characterized by its adaptation to life in the oxic/anoxic interface towards the less saline aerobic waters (mixolimnion) of the stable stratified alkaline salt lakes. Strain ALM 1(T) is the first representative of the genus Thioalkalimicrobium whose genome sequence has been deciphered and the fourth genome sequence of a type strain of the Piscirickettsiaceae to be published. The 1,932,455 bp long chromosome with its 1,684 protein-coding and 50 RNA genes was sequenced as part of the DOE Joint Genome Institute Community Sequencing Program (CSP) 2008. PMID- 27274785 TI - Complete genome sequence of Streptococcus agalactiae strain GBS85147 serotype of type Ia isolated from human oropharynx. AB - Streptococcus agalactiae, also referred to as Group B Streptococcus, is a frequent resident of the rectovaginal tract in humans, and a major cause of neonatal infection. The pathogen can also infect adults with underlying disease, particularly the elderly and immunocompromised ones. In addition, S. agalactiae is a known fish pathogen, which compromises food safety and represents a zoonotic hazard. This study provides valuable structural, functional and evolutionary genomic information of a human S. agalactiae serotype Ia (ST-103) GBS85147 strain isolated from the oropharynx of an adult patient from Rio de Janeiro, thereby representing the first human isolate in Brazil. We used the Ion Torrent PGM platform with the 200 bp fragment library sequencing kit. The sequencing generated 578,082,183 bp, distributed among 2,973,022 reads, resulting in an approximately 246-fold mean coverage depth and was assembled using the Mira Assembler v3.9.18. The S. agalactiae strain GBS85147 comprises of a circular chromosome with a final genome length of 1,996,151 bp containing 1,915 protein coding genes, 18 rRNA, 63 tRNA, 2 pseudogenes and a G + C content of 35.48 %. PMID- 27274787 TI - Screening for Chronic Obstructive Pulmonary Disease in Smoking Cessation Clinic in France. AB - BACKGROUND: The purpose of this study was to detect chronic obstructive pulmonary disease (COPD) among smokers seeking treatment for the first time in a smoking cessation clinic and to assess the predictors of positive screening. METHODS: This study was based on a multicenter survey with questionnaires (Richmond, Fagerstrom, clinical signs) and spirometry miniaturized. Data were analyzed with SAS(r) by Pearson chi-square test, the test of analysis of variance, Spearman correlation coefficient, and multivariate logistic regression step down. FINDINGS: 1918 patients were assessed for eligibility and only 1737 were included. The report forced expiratory volume in 1 second (FEV1/FEV6) was < 0.8 for 33.2% of smokers and < 0.7 for 7.5% of them. People with likely COPD had more dyspnea (P < 0.010) and chronic bronchitis (CB) (P < 0.010). In multivariate analysis, CB, duration of smoking history since longer than 30 years, and dyspnea significantly increased the risk of being detected as COPD. The odds ratios of the above factors were 2.9, 4.1, and 4.5, respectively. CONCLUSION: 7.5% of smokers were likely COPD. Patient's risk factors, such as the presence of CB, smoking addiction for longer than 30 years, or dyspnea, were predictive of a positive screening for COPD. PMID- 27274786 TI - Stress pathways to health inequalities: Embedding ACEs within social and behavioral contexts. AB - OBJECTIVE: This study addresses whether adverse childhood experiences (ACEs) demonstrate disproportional prevalence across demographic- and health-affecting characteristics, offer significant explanation of adult health outcomes, and show patterned association with illness susceptibility early within and across adulthood when viewed in combination with income and psychosocial resources. METHODS: Data were derived from a population-based state health survey using stratified random sampling of household adults (n=7,470): ages 18-99 (M=55), 59.9% females, and race/ethnicity, income and education levels representative of the region. We assessed ACEs by aggregating 8 adversity forms, 5 health behaviors and 3 psychosocial resources; and health outcomes (number of chronic conditions, subjective wellness). RESULTS: Disproportionality was evident in ACEs levels by demographics, adult SES, health behaviors, and psychosocial resources in expected directions. Stepped multiple regressions of health outcomes demonstrated significant betas and R2 change for each predictor block, revealing cumulative as well as unique explanatory utility. Early onset chronic illness was evident on the basis of ACEs levels. These illnesses were amplified for low income respondents. Prevalence was highest across adulthood for those also reporting low psychosocial assets. CONCLUSIONS: Findings offer novel insights as to the "long reach" of childhood adversity on health, conditioned by circumstances under which these effects may occur. Health resilience offered by health behaviors and psychosocial resources should shape thinking about preventive and remedial interventions by social work and allied professionals across a range of settings. PMID- 27274788 TI - Impact of Opium Addiction on Levels of Pro- and Anti-inflammatory Cytokines after Surgery. AB - BACKGROUND: Opium addiction alters immune responses to stresses such as an injury due to changing the secretion of cytokines. The present study assessed the effect of opium addiction on the cytokines [tumor necrosis factor alpha (TNFalpha), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10] before and after laparotomy. METHODS: Male rats were randomly divided into control and opium addicted (n = 20). Then, cytokines were measured before surgery, immediately after surgery (within 30-60 minutes) and 24 hours after surgery. FINDINGS: IFN gamma was raised in an addicted group in three phases of the study as compared to that of the control group. IL-4 in opium addicted group decreased in two phases after surgery compared to the control group. IL-4 was lower after surgery in comparison to before surgery in the opium addicted group. The difference in IL-10 and TNFalpha levels was not statistically significant in the all groups measured in three phases of the investigation. CONCLUSION: The results revealed that opium addiction can increase plasma level of IFN-gamma in rats and decrease plasma level of IL-4 after surgical stress. It seems that opium addicted rats are a more susceptible to increased inflammation. PMID- 27274789 TI - Prevalence of Active and Passive Smoking among Adult Population: Findings of a Population-Based Survey in Kerman (KERCADRS), Iran. AB - BACKGROUND: Smoking is one of the major modifiable risk factors for non communicable diseases. Our aim was to report the pattern of active and passive smoking using the data collected through a population-base household survey in Kerman, Iran [(KERCADRS) Kerman Coronary Artery Disease Risk Factors Study]. METHODS: Using a cluster random sampling design, we recruited 5900 adult persons (15-75 years old) into our survey. After consenting, every participant was interviewed by a trained interviewer. The section for smoking included questions about daily (smoking at least one cigarette per day), non-daily, past and passive cigarette smoking as well as the duration of the exposure. We used Kerman population distribution (as the target population) to adjust our estimates using direct standardization method. FINDINGS: Overall, 8.3% of study participants (15.5% in men vs. 0.8% in women, P = 0.010) reported themselves as daily smokers and an additional 1.7% (2.9% in men vs. 0.4% in women, P = 0.010) as non-daily smokers. The passive smoking was common in total (27.5%), while women experienced more exposure than men (30.1% vs. 25.0%, P = 0.010). In daily smokers, 3.2% smoked more than 20 cigarettes per day. Among passive smokers, 62.6% were exposed to cigarette smoke more than 6 days per week. CONCLUSION: Smoking is pretty common among adult populations, particularly in men. A majority of tobacco-free young adult women are exposed to passive smoking. Age and gender oriented interventions are required to change this risk pattern in Kerman community to prevent from further smoking related morbidities and mortalities. PMID- 27274790 TI - Nicotine Replacement Therapy in Dental Settings: An Exploratory Survey in Bangalore City, India. AB - BACKGROUND: Smoking and other forms of tobacco use remain the most significant worldwide public health problem. The dental practice is being identified as potential location for smoking cessation activity. Nicotine replacement therapy (NRT) promotes the chances of tobacco cessation, however, evidence related to prescription of the NRT in dental settings is lacking. This study aimed to assess and compare the attitudes, practices, beliefs, and barriers in prescribing NRT for tobacco cessation among dental interns and post-graduates (PGs). METHODS: For a cross-sectional survey among 232 participants from 10 dental colleges in Bangalore, India, a 21-item questionnaire was developed: 11-item based on attitudes and practices toward tobacco cessation and 10-items regarding scope and challenges in prescribing NRT. The data were analyzed using descriptive statistics, chi-square test, and test of proportions. FINDINGS: Majority of participants reported ongoing tobacco cessation activity in their college. Statistically significant difference was found between interns and PGs for items related to tobacco cessation practice (assisting, providing follow-up visit). Regarding NRT, significant differences were seen for items related to practice (assisting, assessing motivation for NRT), belief (not an appropriate activity for dentist, a valuable resource, increase in quit attempts) and barriers (bitter taste, cost, and fear of addiction) (P < 0.050). The majority of the PGs suggested cessation center followed by health care workers and pharmacists for the provision of subsidized nicotine gums. CONCLUSION: Favorable practices and beliefs are seen regarding the prescription of NRT among interns and PGs although differences exist. Time, cost, and taste emerged as major barriers. PMID- 27274791 TI - Comparing Time Perception among Morphine-Derived Drugs Addicts and Controls. AB - BACKGROUND: The aim of the present study is to compare time perception among drug addicts and controls. METHODS: 30 drug addicts were selected, and 30 non-addict individuals were selected as the control group. The two groups performed three tests of time reproduction, time estimation, and time discrimination. FINDINGS: There was a significant difference between the addicts group and the control group regarding the error of time reproduction and time estimation. The addict group in comparison to the control group had a lower under-reproduction and a higher over-reproduction error, and also a lower under-estimation and higher over estimation error. However, regarding time discrimination, no significant difference was observed between the errors committed by both groups. On the other hand, when showing images of drug consumption tools and normal images with same durations, the normal group believed that the images related to drug consumption tools were shown for a shorter period of time. CONCLUSION: Time perception is different between morphine-derived drugs addicts and controls. PMID- 27274792 TI - Evaluation of the Prevalence of Drug Abuse and Smoking in Parents of Children with Attention Deficit Hyperactivity Disorder. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) affects 5% of children. In addition to pharmacotherapy, non-drug treatments such as appropriate parenting are also very important in the treatment of these children. Diagnosis and treatment of parents with psychiatric disorders and substance abuse and evaluation of the frequency of these disorders in parents is critical. METHODS: In this case-control study, 200 parents were studied. The target population included parents of 7 to 12 year-old children who referred to child and adolescent psychiatric clinics. The control group included parents of children who referred to child non-psychiatric clinics. The parents were evaluated via a demographic information form, and structured interviews based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) for nicotine and drug addiction. Then, the Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HDRS) was used to assess their anxiety and depression. FINDINGS: Among the studied parents, the comparison of drug abuse, smoking, and stress showed significant differences between the two groups. In terms of depression and ADHD, the difference between the case and control groups was not statistically significant. CONCLUSION: The higher prevalence of these disorders in parents of children with ADHD may indicate the possible role of this disorder in the etiology. PMID- 27274793 TI - Relapse and Risk-taking among Iranian Methamphetamine Abusers Undergoing Matrix Treatment Model. AB - BACKGROUND: This study investigated the correlation between risk-taking and relapse among methamphetamine (MA) abusers undergoing the Matrix Model of treatment. METHODS: This cross-sectional study was conducted on male patients who were stimulant drug abusers undergoing the matrix treatment in the National Center for Addiction Research. A sampling was done using the availability method including 92 male patients. Demographic questionnaires and drug abuse related questionnaire were completed for each patient. Then, Bart's balloon risk-taking test was administered to the patients. FINDINGS: Participants had a mean age +/- standard deviation (SD) of 27.59 +/- 6.60 years with an age range of 17-29 years. Unemployment, unmarried status, criminal offense, and also addiction family history increased the probability of relapse. In addition, a greater adjusted score of the risk-taking test increased the odds of relapse by more than 97%. The simultaneous abuse of opium and stimulants compared to the abuse of stimulants only, revealed no statistically significant differences for relapse. Patients with higher risk-taking behavior had a more probability of relapse. CONCLUSION: This finding indirectly implies the usefulness of Bart's risk-taking test in assessing risk-taking behavior in stimulant drug abusers. PMID- 27274794 TI - Predisposing Factors for Methadone Poisoning in Children Hospitalized at Kerman Afzalipour Hospital, Iran. AB - BACKGROUND: Methadone is a synthetic opioid that has been used to relieve severe pain in addiction withdrawal. Unfortunately, due to non-standard supply and storage, the incidence of poisoning and deaths caused by this drug is increasing daily. The purpose of this study was to determine the underlying causes of methadone poisoning in children admitted to Kerman Afzalipour Hospital, Kerman University of Medical Sciences, Iran, during 2012. METHODS: This cross-sectional study was performed on 105 children diagnosed with methadone poisoning and admitted to the pediatric emergency ward at Kerman Afzalipour Hospital. The required information was recorded through interviews with parents, patient examination, and if necessary telephone calls with the parents. The data were analyzed using SPSS software. FINDINGS: Mean age of children was 3.9 +/- 2.4 years and 59.0% of them were boys. Most parents had a high school diploma or a lower level of education. In all cases, a family member or relative, or at least one person in a party they attended was an addict. In most cases, methadone was fed to the child by mistake instead of water or other drugs. Parental substance abuse, employment status, and family income were significantly associated with methadone poisoning. CONCLUSION: Training of methadone storage in individuals who need to use this drug can help to prevent accidental ingestion and poisoning of children. PMID- 27274795 TI - Effective Interventions to Improve Triangular Clinic Services. PMID- 27274796 TI - Leaf cellulose density as the key determinant of inter- and intra-specific variation in leaf fracture toughness in a species-rich tropical forest. AB - Leaves as the main photosynthetic organ of plants must be well protected against various hazards to achieve their optimal lifespans. Yet, within-species variation and the material basis of leaf strength have been explored for very few species. Here, we present a large dataset of leaf fracture toughness from a species-rich humid tropical forest on Barro Colorado Island, Panama, reporting both among- and within-species variation in relation to light environment (sun-lit canopy versus shaded understorey) and ontogeny (seedlings versus adults). In this dataset encompassing 281 free-standing woody species and 428 species-light combinations, lamina fracture toughness varied ca 10 times. A central objective of our study was to identify generalizable patterns in the structural and material basis for interspecific variation in leaf lamina fracture toughness. The leaf lamina is a heterogeneous structure in which strong materials in cell walls, such as cellulose and lignin, contribute disproportionately to fracture toughness. We found significant increases in leaf fracture toughness from shade to sun and from seedling leaves to adult leaves. Both within and across species, leaf fracture toughness increased with total bulk density (dry biomass per unit volume) and cellulose mass concentration, but decreased with mass concentrations of lignin and hemicelluose. These bivariate relationships shift between light environments, but leaf cellulose density (cellulose mass per unit leaf volume) exhibits a common relationship with lamina fracture toughness between light environments and through ontogeny. Hence, leaf cellulose density is probably a universal predictor of leaf fracture toughness. PMID- 27274797 TI - Minimally disruptive needle insertion: a biologically inspired solution. AB - The mobility of soft tissue can cause inaccurate needle insertions. Particularly in steering applications that employ thin and flexible needles, large deviations can occur between pre-operative images of the patient, from which a procedure is planned, and the intra-operative scene, where a procedure is executed. Although many approaches for reducing tissue motion focus on external constraining or manipulation, little attention has been paid to the way the needle is inserted and actuated within soft tissue. Using our biologically inspired steerable needle, we present a method of reducing the disruptiveness of insertions by mimicking the burrowing mechanism of ovipositing wasps. Internal displacements and strains in three dimensions within a soft tissue phantom are measured at the needle interface, using a scanning laser-based image correlation technique. Compared to a conventional insertion method with an equally sized needle, overall displacements and strains in the needle vicinity are reduced by 30% and 41%, respectively. The results show that, for a given net speed, needle insertion can be made significantly less disruptive with respect to its surroundings by employing our biologically inspired solution. This will have significant impact on both the safety and targeting accuracy of percutaneous interventions along both straight and curved trajectories. PMID- 27274798 TI - Fundamentals of cutting. AB - The process of cutting is analysed in fracture mechanics terms with a view to quantifying the various parameters involved. The model used is that of orthogonal cutting with a wedge removing a layer of material or chip. The behaviour of the chip is governed by its thickness and for large radii of curvature the chip is elastic and smooth cutting occurs. For smaller thicknesses, there is a transition, first to plastic bending and then to plastic shear for small thicknesses and smooth chips are formed. The governing parameters are tool geometry, which is principally the wedge angle, and the material properties of elastic modulus, yield stress and fracture toughness. Friction can also be important. It is demonstrated that the cutting process may be quantified via these parameters, which could be useful in the study of cutting in biology. PMID- 27274799 TI - Cutting food in terrestrial carnivores and herbivores. AB - Insects and mammals cut their food up into small pieces to facilitate ingestion and chemical digestion. Teeth and jaws act as cutting tools, but, unlike engineering tools designed for a specific purpose, must generally cope with substantial variation in food properties and work at many scales. Knowing how teeth and jaws work effectively requires an understanding of the cutting on the edges and the mechanisms that remove cut material. Variability and heterogeneity of diet properties are not well known, and, for example, may be higher and overlap more in the browsing and grazing categories of plant diets. A reinterpretation of tooth function in large mammal browsers and grazers is proposed. PMID- 27274800 TI - Numerical modelling of orthogonal cutting: application to woodworking with a bench plane. AB - A numerical model for orthogonal cutting using the material point method was applied to woodcutting using a bench plane. The cutting process was modelled by accounting for surface energy associated with wood fracture toughness for crack growth parallel to the grain. By using damping to deal with dynamic crack propagation and modelling all contact between wood and the plane, simulations could initiate chip formation and proceed into steady-state chip propagation including chip curling. Once steady-state conditions were achieved, the cutting forces became constant and could be determined as a function of various simulation variables. The modelling details included a cutting tool, the tool's rake and grinding angles, a chip breaker, a base plate and a mouth opening between the base plate and the tool. The wood was modelled as an anisotropic elastic-plastic material. The simulations were verified by comparison to an analytical model and then used to conduct virtual experiments on wood planing. The virtual experiments showed interactions between depth of cut, chip breaker location and mouth opening. Additional simulations investigated the role of tool grinding angle, tool sharpness and friction. PMID- 27274801 TI - Point of impact: the effect of size and speed on puncture mechanics. AB - The use of high-speed puncture mechanics for prey capture has been documented across a wide range of organisms, including vertebrates, arthropods, molluscs and cnidarians. These examples span four phyla and seven orders of magnitude difference in size. The commonality of these puncture systems offers an opportunity to explore how organisms at different scales and with different materials, morphologies and kinematics perform the same basic function. However, there is currently no framework for combining kinematic performance with cutting mechanics in biological puncture systems. Our aim here is to establish this framework by examining the effects of size and velocity in a series of controlled ballistic puncture experiments. Arrows of identical shape but varying in mass and speed were shot into cubes of ballistic gelatine. Results from high-speed videography show that projectile velocity can alter how the target gel responds to cutting. Mixed models comparing kinematic variables and puncture patterns indicate that the kinetic energy of a projectile is a better predictor of penetration than either momentum or velocity. These results form a foundation for studying the effects of impact on biological puncture, opening the door for future work to explore the influence of morphology and material organization on high-speed cutting dynamics. PMID- 27274802 TI - Root dentine and endodontic instrumentation: cutting edge microscopic imaging. AB - Cutting of the dental hard tissues is an integral part of restorative dentistry. Cutting of the root dentine is also needed in preparation prior to endodontic treatment, with significant commercial investment for the development of flexible cutting instruments based around nickel titanium (NiTi) alloys. This paper describes the evolution of endodontic cutting instruments, both in materials used, e.g. the transition from stainless steel to NiTi, and the design of the actual instruments themselves and their method of activation-by hand or motor driven. We have been examining tooth-cutting interactions microscopically for over 25 years using a variety of microscopic techniques; in particular, video rate confocal microscopy. This has given a unique insight into how many of the procedures that we take for granted are achieved in clinical practice, by showing microscopic video images of the cutting as it occurs within the tooth. This technology has now been extended to allow imaging of the endodontic instrument and the root canal wall for the first time. We are able to image dentine distortion and crack propagation during endodontic filing of the root canal space. We are also able to visualize the often claimed, but seldom seen action of contemporary endodontic instruments. PMID- 27274804 TI - Is fracture a bigger problem for smaller animals? Force and fracture scaling for a simple model of cutting, puncture and crushing. AB - Many of the materials that are challenging for large animals to cut or puncture are also cut and punctured by much smaller organisms that are limited to much smaller forces. Small organisms can overcome their force limitations by using sharper tools, but one drawback may be an increased susceptibility to fracture. We use simple contact mechanics models to estimate how much smaller the diameter of the tips or edges of tools such as teeth, claws and cutting blades must be in smaller organisms in order for them to puncture or cut the same materials as larger organisms. In order to produce the same maximum stress when maximum force scales as the square of body length, the diameter of the tool region that is in contact with the target material must scale isometrically for punch-like tools (e.g. scorpion stings) on thick targets, and for crushing tools (e.g. molars). For punch-like tools on thin targets, and for cutting blades on thick targets, the tip or edge diameters must be even smaller than expected from isometry in smaller animals. The diameters of a small sample of unworn punch-like tools from a large range of animal sizes are consistent with the model, scaling isometrically or more steeply (positively allometric). In addition, we find that the force required to puncture a thin target using real biological tools scales linearly with tip diameter, as predicted by the model. We argue that, for smaller tools, the minimum energy to fracture the tool will be a greater fraction of the minimum energy required to puncture the target, making fracture more likely. Finally, energy stored in tool bending, relative to the energy to fracture the tool, increases rapidly with the aspect ratio (length/width), and we expect that smaller organisms often have to employ higher aspect ratio tools in order to puncture or cut to the required depth with available force. The extra stored energy in higher aspect ratio tools is likely to increase the probability of fracture. We discuss some of the implications of the suggested scaling rules and possible adaptations to compensate for fracture sensitivity in smaller organisms. PMID- 27274803 TI - How chimpanzees integrate sensory information to select figs. AB - Figs are keystone resources that sustain chimpanzees when preferred fruits are scarce. Many figs retain a green(ish) colour throughout development, a pattern that causes chimpanzees to evaluate edibility on the basis of achromatic accessory cues. Such behaviour is conspicuous because it entails a succession of discrete sensory assessments, including the deliberate palpation of individual figs, a task that requires advanced visuomotor control. These actions are strongly suggestive of domain-specific information processing and decision making, and they call attention to a potential selective force on the origin of advanced manual prehension and digital dexterity during primate evolution. To explore this concept, we report on the foraging behaviours of chimpanzees and the spectral, chemical and mechanical properties of figs, with cutting tests revealing ease of fracture in the mouth. By integrating the ability of different sensory cues to predict fructose content in a Bayesian updating framework, we quantified the amount of information gained when a chimpanzee successively observes, palpates and bites the green figs of Ficus sansibarica. We found that the cue eliciting ingestion was not colour or size, but fig mechanics (including toughness estimates from wedge tests), which relays higher-quality information on fructose concentrations than colour vision. This result explains why chimpanzees evaluate green figs by palpation and dental incision, actions that could explain the adaptive origins of advanced manual prehension. PMID- 27274805 TI - Fracture investigation in starch-based foods. AB - The study of oral processing and specifically cutting of the food piece during mastication can lead towards optimization of products for humans or animals. Food materials are complex biocomposites with a highly nonlinear constitutive response. Their fracture properties have not been largely investigated, while the need for models capable of predicting food breakdown increases. In this study, the blade cutting and the essential work of fracture (EWF) methodologies assessed the fracture behaviour of starch-based pet food. Tensile tests revealed rate dependent stiffness and stress softening effects, attributed to viscoplasticity and micro-cracking, respectively. Cutting data were collected for 5, 10 and 30 mm s(-1) sample feed rates, whereas the EWF tests were conducted at 1.7, 3.3 and 8.3 mm s(-1) crosshead speeds corresponding to average crack speeds of 4, 7 and 15 mm s(-1), respectively. A reasonable agreement was achieved between cutting and EWF, reporting 1.26, 1.78, 1.76 kJ m(-2) and 1.52, 1.37, 1.45 kJ m(-2) values, respectively, for the corresponding crack speeds. These toughness data were used in a novel numerical model simulating the 'first' bite mastication process. A viscoplastic material model is adopted for the food piece, combined with a damage law that enabled predicting fracture patterns in the product. PMID- 27274806 TI - Cut marks on bone surfaces: influences on variation in the form of traces of ancient behaviour. AB - Although we know that our lineage has been producing sharp-edged tools for over 2.6 Myr, our knowledge of what they were doing with these tools is far less complete. Studies of these sharp-edged stone tools show that they were most probably used as cutting implements. However, the only substantial evidence of this is the presence of cut marks on the bones of animals found in association with stone tools in ancient deposits. Numerous studies have aimed to quantify the frequency and placement of these marks. At present there is little consensus on the meaning of these marks and how the frequency relates to specific behaviours in the past. Here we investigate the possibility that mechanical properties associated with edges of stone tools as well as the properties of bones themselves may contribute to the overall morphology of these marks and ultimately their placement in the archaeological record. Standardized tests of rock mechanics (Young's modulus and Vickers hardness) indicate that the hardness of tool edges significantly affects cut-mark morphology. In addition, we show that indentation hardness of bones also impacts the overall morphology of cut marks. Our results show that rock type and bone portions influence the shape and prevalence of cut marks on animal bones. PMID- 27274808 TI - Slice-push, formation of grooves and the scale effect in cutting. AB - Three separate aspects of cutting are investigated which complement other papers on the mechanics of separation processes presented at this interdisciplinary Theo Murphy meeting. They apply in all types of cutting whether blades are sharp or blunt, and whether the material being cut is 'hard, stiff and strong' or 'soft, compliant and weak'. The first topic discusses why it is easier to cut when there is motion along (parallel to) the blade as well motion across (perpendicular to) the cutting edge, and the analysis is applied to optimization of blade geometries to produce minimum cutting forces and hence minimum damage to cut surfaces. The second topic concerns cutting with more than one edge with particular application to the formation of grooves in surfaces by hard pointed tools. The mechanics are investigated and applied to the topic of abrasive wear by hard particles. Traditional analyses say that abrasive wear resistance increases monotonically with the hardness of the workpiece, but we show that the fracture toughness of the surface material is also important, and that behaviour is determined by the toughness-to-hardness ratio rather than hardness alone. Scaling forms the third subject. As cutting is a branch of elasto-plastic fracture mechanics, cube-square energy scaling applies in which the important length scale is (ER/k (2)), where E is Young's modulus, R is the fracture toughness and k is the shear yield strength. Whether, in cutting, material is removed as ductile ribbons, as semi ductile discontinuous chips, or by brittle 'knocking lumps out' is shown to depend on the depth of cut relative to this characteristic length parameter. Scaling in biology is called allometry and its relationship with engineering scaling is discussed. Some speculative predictions are made in relation to the action of teeth on food. PMID- 27274807 TI - Dental abrasion as a cutting process. AB - A mammalian tooth is abraded when a sliding contact between a particle and the tooth surface leads to an immediate loss of tooth tissue. Over time, these contacts can lead to wear serious enough to impair the oral processing of food. Both anatomical and physiological mechanisms have evolved in mammals to try to prevent wear, indicating its evolutionary importance, but it is still an established survival threat. Here we consider that many wear marks result from a cutting action whereby the contacting tip(s) of such wear particles acts akin to a tool tip. Recent theoretical developments show that it is possible to estimate the toughness of abraded materials via cutting tests. Here, we report experiments intended to establish the wear resistance of enamel in terms of its toughness and how friction varies. Imaging via atomic force microscopy (AFM) was used to assess the damage involved. Damage ranged from pure plastic deformation to fracture with and without lateral microcracks. Grooves cut with a Berkovich diamond were the most consistent, suggesting that the toughness of enamel in cutting is 244 J m( 2), which is very high. Friction was higher in the presence of a polyphenolic compound, indicating that this could increase wear potential. PMID- 27274809 TI - Correction to 'Collagen network strengthening following cyclic tensile loading'. AB - [This corrects the article DOI: 10.1098/rsfs.2015.0088.]. PMID- 27274810 TI - Lmod2 piggyBac mutant mice exhibit dilated cardiomyopathy. AB - BACKGROUND: Leiomodin proteins, Lmod1, Lmod2 and Lmod3, are key regulators of the thin filament length in muscles. While Lmod1 is specifically expressed in smooth muscles, both Lmod2 and Lmod3 are expressed in striated muscles including both cardiac and skeletal muscles. We and others have previously shown that Lmod3 mainly function in skeletal muscles and the mutant mice display disorganized sarcomere. Lmod2 protein has been found to act as an actin filament nucleator in both cell-free assays and in cultured rat and chicken cardiomyocytes. RESULTS: To better understand the function of Lmod2 in vivo, we have identified and characterized a piggyBac (PB) insertional mouse mutant. Our analysis revealed that the PB transposon inserts in the first exon of the Lmod2 gene and severely disrupts its expression. We found that Lmod2 (PB/PB) mice exhibit typical dilated cardiomyopathy (DCM) with ventricular arrhythmias and postnatal lethality. Electron microscope reveals that the Lmod2 (PB/PB) hearts carry disordered sarcomere, disarrayed thin filaments, and distorted intercalated discs (ICDs). Those ICDs display not only decreased convolutions, but also reduced electron dense staining, indicating less ICDs component proteins in Lmod2 (PB/PB) hearts. Consistent with the phenotype, the expression of the ICD component genes, beta catenin and Connexin43, are down-regulated. CONCLUSIONS: Taken together, our data reveal that Lmod2 is required in heart thin filaments for integrity of sarcomere and ICD and deficient mice exhibit DCM with ventricular arrhythmias and postnatal lethality. The Lmod2 (PB/PB) mutant offers a valuable resource for interrogation of pathogenesis and development of therapeutics for DCM. PMID- 27239267 TI - Case Report: A case report of dry tap during ventriculostomy. AB - Pneumocephalus following ventriculoperitoneal (VP) shunt insertion is an exceptionally rare occurrence. We report such an event after attempting ventricular puncture (ventriculostomy) for VP shunt insertion and then discuss the management of the same. Dry tap can lead to multiple attempts for ventriculostomy with the associated added risks of complications, as well as complicating the subsequent management. In addition, there is an increased risk of tension pneumocephalus, seizure and shunt failure due to a blockage by air bubbles. Our patient presented with features of raised intracranial pressure two months following craniotomy and evacuation of traumatic subdural hematoma. External ventricular puncture revealed egress of CSF under pressure. Upon attempting VP shunting for post-traumatic hydrocephalus, we experienced dry tap during ventricular puncture that complicated further management. We placed the proximal shunt in the presumed location of the foramen of Monro of ipsilateral frontal horn of lateral ventricle and did not remove the external ventricular drain. Post-operative CT scan revealed pneumoventriculi as the cause for the dry tap during ventricular puncture. Patient was managed with 100% oxygen. He showed gradual improvement and was later discharged. This case shows that variations in the procedure, including head down positioning, adequate cruciate dural incision prior to cortex puncture, and avoiding excessive egress of CSF can help to prevent such complications. PMID- 27274811 TI - Absence of Cytotoxicity towards Microglia of Iron Oxide (alpha-Fe2O3) Nanorhombohedra. AB - Understanding the nature of interactions between nanomaterials, such as commercially ubiquitous hematite (alpha-Fe2O3) Nanorhombohedra (N-Rhomb) and biological systems is of critical importance for gaining insight into the practical applicability of nanomaterials. Microglia represent the first line of defense in the central nervous system (CNS) during severe injury or disease such as Parkinson's and Alzheimer's disease as illustrative examples. Hence, to analyze the potential cytotoxic effect of nanorhombohedra exposure in the presence of microglia, we have synthesized Rhodamine B (RhB) labeled-alpha-Fe2O3 N-Rhomb, with lengths of 47 +/- 10 nm and widths of 35 +/- 8 nm. Internalization of RhB labeled-alpha-Fe2O3 N-Rhomb by microglia in the mouse brain was observed, and a dose-dependent increase in the cellular iron content as probed by cellular fluorescence was detected in cultured microglia after nanoparticle exposure. The cells maintained clear functional viability, exhibiting little to no cytotoxic effects after 24 and 48 hours at acceptable, physiological concentrations. Importantly, the nanoparticle exposure did not induce microglial cells to produce either tumor necrosis factor alpha (TNFalpha) or interleukin 1-beta (IL1beta), two pro-inflammatory cytokines, nor did exposure induce the production of nitrites and reactive oxygen species (ROS), which are common indicators for the onset of inflammation. Finally, we propose that under the conditions of our experiments, i.e. in the presence of RhB labeled-alpha-Fe2O3 N-Rhomb maintaining concentrations of up to 100 ug/mL after 48 hours of incubation, the in vitro and in vivo internalization of RhB labeled-alpha-Fe2O3 N-Rhomb are likely to be clathrin-dependent, which represents a conventional mechanistic uptake route for most cells. Given the crucial role that microglia play in many neurological disorders, understanding the potential cytotoxic effects of these nanostructures is of fundamental importance if they are to be used in a therapeutic setting. PMID- 27239268 TI - Enteropathogenic E. coli: breaking the intestinal tight junction barrier. AB - Enteropathogenic E. coli (EPEC) causes acute intestinal infections in infants in the developing world. Infection typically spreads through contaminated food and water and leads to severe, watery diarrhea. EPEC attaches to the intestinal epithelial cells and directly injects virulence factors which modulate multiple signaling pathways leading to host cell dysfunction. However, the molecular mechanisms that regulate the onset of diarrhea are poorly defined. A major target of EPEC is the host cell tight junction complex which acts as a barrier and regulates the passage of water and solutes through the paracellular space. In this review, we focus on the EPEC effectors that target the epithelial barrier, alter its functions and contribute to leakage through the tight junctions. PMID- 27274814 TI - The potential of plants as a system for the development and production of human biologics. AB - The growing promise of plant-made biologics is highlighted by the success story of ZMappTM as a potentially life-saving drug during the Ebola outbreak of 2014 2016. Current plant expression platforms offer features beyond the traditional advantages of low cost, high scalability, increased safety, and eukaryotic protein modification. Novel transient expression vectors have been developed that allow the production of vaccines and therapeutics at unprecedented speed to control potential pandemics or bioterrorism attacks. Plant-host engineering provides a method for producing proteins with unique and uniform mammalian post translational modifications, providing opportunities to develop biologics with increased efficacy relative to their mammalian cell-produced counterparts. Recent demonstrations that plant-made proteins can function as biocontrol agents of foodborne pathogens further exemplify the potential utility of plant-based protein production. However, resolving the technical and regulatory challenges of commercial-scale production, garnering acceptance from large pharmaceutical companies, and obtaining U.S. Food and Drug Administration approval for several major classes of biologics are essential steps to fulfilling the untapped potential of this technology. PMID- 27274815 TI - Cholera outbreak caused by drug resistant Vibrio cholerae serogroup O1 biotype ElTor serotype Ogawa in Nepal; a cross-sectional study. AB - BACKGROUND: Cholera is a major cause of mortality and morbidity in underdeveloped countries including Nepal. Recently drug resistance in Vibrio cholerae has become a serious problem mainly in developing countries. The main objectives of our study were to investigate the occurrence of Vibrio cholerae in stool samples from patients with watery diarrhea and to determine the antimicrobial susceptibility patterns of V. cholerae isolates. METHODS: A total of 116 stool samples from patients suffering from watery diarrhea during July to December 2012 were obtained from outbreak areas from all over Nepal. Alkaline peptone water and thiosulphate citrate bile salt sucrose agar (TCBS) were used to isolate the Vibrio cholerae. The isolates were identified with the help of colony morphology, Gram's staining, conventional biochemical testing, serotyping and biotyping. Antimicrobial susceptibility testing was performed by determining the minimum inhibitory concentration (MIC) by agar dilution method. RESULTS: Vibrio cholerae was isolated from 26.72 % of total samples. All isolated Vibrio cholerae were confirmed to be Vibrio cholerae serogoup O1 biotype El Tor and serotype Ogawa. All isolates were resistant to ampicillin and cotrimoxazole. Twenty nine isolates were resistant toward two different classes of antibiotics, one strain was resistant to three different classes of antibiotics and one strain was resistant to four different classes of antibiotics. According to the definition of the multidrug resistant bacteria; 6.45 % of the strains of Vibrio cholerae were found to be multidrug resistant. CONCLUSIONS: Cholera due to multidrug resistant Vibrio cholerae is also possible in Nepal. According to the antimicrobial susceptibility pattern of Vibrio cholerae in our study we recommend to use any antibiotics among tetracycline, doxycycline, levofloxacin, azithromycin, chloramphenicol and ciprofloxacin for preliminary treatment of cholera in Nepal. PMID- 27274816 TI - Feasibility of a hemodialysis safety checklist for nurses and patients: a quality improvement study. AB - BACKGROUND: Patients with end-stage renal disease are at high risk for medical errors given their comorbidities, polypharmacy and coordination of care with other hospital departments. We previously developed a hemodialysis safety checklist (Hemo Pause) to be jointly completed by nurses and patients. Our objective was to determine the feasibility of using this checklist during every hemodialysis session for 3 months. METHODS: We conducted a single-center, prospective time series study. A convenience sample of 14 nurses and 22 prevalent in-center hemodialysis patients volunteered to participate. All participants were trained in the administration of the Hemo Pause checklist. The primary outcome was completion of the Hemo Pause checklist, which was assessed at weekly intervals. We also measured the acceptability of the Hemo Pause checklist using a local patient safety survey. RESULTS: There were 799 hemodialysis treatments pre intervention (13 January-5 April 2014) and 757 post-intervention (5 May-26 July 2014). The checklist was completed for 556 of the 757 (73%) treatments. Among the hemodialysis nurses, 93% (13/14) agreed that the checklist was easy to use and 79% (11/14) agreed it should be expanded to other patients. Among the hemodialysis patients, 73% (16/22) agreed that the checklist made them feel safer and should be expanded to other patients. CONCLUSIONS: The Hemo Pause safety checklist was acceptable to both nurses and patients over 3 months. Our next step is to spread this checklist locally and conduct a mixed methods study to determine mechanisms by which its use may improve safety culture and reduce adverse events. PMID- 27274817 TI - Omics databases on kidney disease: where they can be found and how to benefit from them. AB - In the recent decades, the evolution of omics technologies has led to advances in all biological fields, creating a demand for effective storage, management and exchange of rapidly generated data and research discoveries. To address this need, the development of databases of experimental outputs has become a common part of scientific practice in order to serve as knowledge sources and data sharing platforms, providing information about genes, transcripts, proteins or metabolites. In this review, we present omics databases available currently, with a special focus on their application in kidney research and possibly in clinical practice. Databases are divided into two categories: general databases with a broad information scope and kidney-specific databases distinctively concentrated on kidney pathologies. In research, databases can be used as a rich source of information about pathophysiological mechanisms and molecular targets. In the future, databases will support clinicians with their decisions, providing better and faster diagnoses and setting the direction towards more preventive, personalized medicine. We also provide a test case demonstrating the potential of biological databases in comparing multi-omics datasets and generating new hypotheses to answer a critical and common diagnostic problem in nephrology practice. In the future, employment of databases combined with data integration and data mining should provide powerful insights into unlocking the mysteries of kidney disease, leading to a potential impact on pharmacological intervention and therapeutic disease management. PMID- 27274818 TI - The cell cycle biomarkers: promising research, but do not oversell them. AB - This review focuses on the most recent scientific and clinical information on the development and clinical applicability of the cell cycle biomarkers TIMP-2 and IGFBP-7 in the diagnosis and prognosis of patients at risk for and suffering from acute kidney injury (AKI). A number of evaluation studies have demonstrated that compared with existing biomarkers, urinary excretion of the product of both biomarkers, [TIMP-2]*[IGFBP-7], improved diagnostic performance in assessing the risk for AKI, predicting the need for renal replacement therapy, AKI-related complications and short- and long-term prognoses. The reference intervals for these biomarkers, measured by the recently approved NephroCheck test, have been determined in apparently healthy adults and those with stable chronic morbid conditions without AKI. This review recognizes that the combination of these two cell cycle arrest markers for the early detection of AKI is promising but concludes that its clinical impact is still unproved. Clinicians should understand the utility and limitations of this test before deciding whether to make it available at their institution. PMID- 27274820 TI - Fat tissue and inflammation in patients undergoing peritoneal dialysis. AB - BACKGROUND: Body weight has been increasing in the general population and is an established risk factor for hypertension, diabetes, and all-cause and cardiovascular mortality. Patients undergoing peritoneal dialysis (PD) gain weight, mainly during the first months of treatment. The aim of this study was to assess the relationship between body composition and metabolic and inflammatory status in patients undergoing PD. METHODS: This was a prospective, non interventional study of prevalent patients receiving PD. Body composition was studied every 3 months using bioelectrical impedance (BCM((r))). We performed linear regression for each patient, including all BCM((r)) measurements, to calculate annual changes in body composition. Thirty-one patients in our PD unit met the inclusion criteria. RESULTS: Median follow-up was 26 (range 17-27) months. Mean increase in weight was 1.8 +/- 2.8 kg/year. However, BCM((r)) analysis revealed a mean increase in fat mass of 3.0 +/- 3.2 kg/year with a loss of lean mass of 2.3 +/- 4.1 kg/year during follow-up. The increase in fat mass was associated with the conicity index, suggesting that increases in fat mass are based mainly on abdominal adipose tissue. Changes in fat mass were directly associated with inflammation parameters such as C-reactive protein (r = 0.382, P = 0.045) and inversely associated with high-density lipoprotein cholesterol (r= 0.50, P = 0.008). CONCLUSIONS: Follow-up of weight and body mass index can underestimate the fat mass increase and miss lean mass loss. The increase in fat mass is associated with proinflammatory state and alteration in lipid profile. PMID- 27274819 TI - Adipocytokines in renal transplant recipients. AB - In the last two decades, perceptions about the role of body fat have changed. Adipocytes modulate endocrine and immune homeostasis by synthesizing hundreds of hormones, known as adipocytokines. Many studies have been investigating the influences and effects of these adipocytokines and suggest that they are modulated by the nutritional and immunologic milieu. Kidney transplant recipients (KTRs) are a unique and relevant population in which the function of adipocytokines can be examined, given their altered nutritional and immune status and subsequent dysregulation of adipocytokine metabolism. In this review, we summarize the recent findings about four specific adipocytokines and their respective roles in KTRs. We decided to evaluate the most widely described adipocytokines, including leptin, adiponectin, visfatin and resistin. Increasing evidence suggests that these adipocytokines may lead to cardiovascular events and metabolic changes in the general population and may also increase mortality and graft loss rate in KTRs. In addition, we present findings on the interrelationship between serum adipocytokine levels and nutritional and immunologic status, and mechanisms by which adipocytokines modulate morbidity and outcomes in KTRs. PMID- 27274822 TI - Efficacy and safety of adrenocorticotropic hormone treatment in glomerular diseases: a systematic review and meta-analysis. AB - BACKGROUND: There is growing evidence that adrenocorticotropic hormone (ACTH) may be effective in treating various forms of glomerular diseases. However, the efficacy of treatment and frequency of adverse effects associated with the use of ACTH in glomerular diseases are unknown. A systematic review and meta-analysis of the literature was performed. METHODS: A literature search was performed using Medline, Embase, Google Scholar and the Cochrane Database of Systematic Reviews from inception through 18 July 2015. Studies assessing the efficacy and safety of ACTH treatment in adults with glomerular diseases were included. RESULTS: Of the 343 identified citations, 18 evaluated the drug efficacy and 12 evaluated the adverse effects. The most common glomerular diseases were membranous nephropathy (MN), primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). The overall rate of complete remission in MN was 80% at 0-6 months, 69% at >6-12 months, 90% at >12-24 months and 95% beyond 24 months of follow-up. Fifty percent of primary FSGS and MCD patients treated with ACTH were in remission at 6 months, but the relapse rate was high after ACTH discontinuation (17%). Evidence of ACTH efficacy for other glomerular diseases was scarce. Edema was the most commonly reported adverse effect {incidence rate [IR] 0.10 [95% confidence interval (CI) 0.04-0.18]} followed by insomnia [IR 0.08 (95% CI 0.03-0.15)]. The dropout rate due to adverse events was 7%, mostly due to edema and weight gain. CONCLUSIONS: ACTH is a well-tolerated therapy and is most promising when treating patients with MN. There may be a potential role for ACTH in patients with MCD and FSGS, but data are lacking. PMID- 27274821 TI - Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis. AB - BACKGROUND: Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence-practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. METHODS: Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. RESULTS: We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 +/- 13.2 weeks and the mean global duration was 38 +/- 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = -0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 +/- 1.6 versus 1.56 +/- 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients. CONCLUSIONS: We found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected. PMID- 27274823 TI - Revisiting post-infectious glomerulonephritis in the emerging era of C3 glomerulopathy. AB - BACKGROUND: Post-infectious glomerulonephritis (PIGN) is an immune complex mediated glomerular injury that typically resolves. Dominant C3 deposition is characteristic of PIGN, but with the emergence of C3 glomerulonephritis (C3GN) as a distinct entity, it is unclear how the pathologic similarities between PIGN and C3GN should be reconciled. Therefore, nephrologists and nephropathologists need additional guidance at the time of biopsy. METHODS: We studied 23 pediatric and young adult patients diagnosed with PIGN. Patients were divided into two groups, one with co-dominance between C3 and immunoglobulins and the other meeting proposed diagnostic criteria for C3GN. Clinical and pathological features were compared. RESULTS: No clinical and/or pathological features could distinguish between those with C3-co-dominant deposits and those with C3 dominance. Nearly all patients in both groups regained their baseline renal function without clinical intervention. CONCLUSIONS: Although the identification of abnormalities of the alternative pathway of complement is characteristic of C3GN, testing is not widely available and the turnaround time often exceeds 1 month. Our study found that PIGN with either co-dominant or dominant C3 deposition in a cohort of young patients has excellent short-term outcomes. Close clinical observation for persistent abnormalities, such as hypocomplementemia, prolonged hematuria or proteinuria, is recommended to single out patients that may harbor intrinsic complement abnormalities. PMID- 27274824 TI - Kidney transplant outcomes in familial C3 glomerulopathy. AB - C3 glomerulopathy, a newly designated entity, is characterized by glomerular disease associated with dysregulation of the alternative complement pathway and is a rare cause of end-stage kidney disease. Overall disease characteristics that include clinical presentation, laboratory assessment, histopathology and genetic background have only been unravelled in recent years and have led to the development of anti-complement therapies targeting different levels of the alternative pathway. We describe the long-term outcomes following kidney transplantation in an Irish family with familial C3 glomerulopathy due to a hybrid CFHR3-1 gene. PMID- 27274825 TI - Recurrent focal segmental glomerulosclerosis apparently resistant to plasmapheresis improves after surgical repair of arteriovenous fistula aneurysms. AB - Focal segmental glomerulosclerosis (FSGS) is a leading cause of end-stage renal disease and has a high recurrence rate after kidney transplantation, attributed to a circulating permeability factor. Plasmapheresis is the treatment of choice after recurrence to remove the circulating factor. We present a case of recurrent FSGS 6 years after transplantation. It is instructive because proteinuria did not respond to intensive plasmapheresis-combined with rituximab-until the possibility of ineffective apheresis secondary to multiple aneurysms in the arteriovenous fistula (AVF) was considered. Proteinuria improved soon after alternative access for plasmapheresis was secured and AVF aneurysms were surgically repaired. PMID- 27274826 TI - Severe acute interstitial nephritis after combination immune-checkpoint inhibitor therapy for metastatic melanoma. AB - Immune-checkpoint inhibitors are emerging as revolutionary drugs for certain malignancies. However, blocking the co-inhibitory signals may lead to immune related adverse events, mainly in the spectrum of autoimmune diseases including colitis, endocrinopathies and nephritis. Here, we report a case of a 75-year-old man with metastatic malignant melanoma treated with a combination of nivolumab (anti-PD1-antibody) and ipilimumab (anti-CTLA-4 antibody) who developed systemic rash along with severe acute tubulointerstitial nephritis after two doses of combination therapy. Kidney biopsy and peripheral blood immune profile revealed highly proliferative and cytotoxic T cell features. Herein, we discuss the pathophysiology and management of immune checkpoint blockade-related adverse events. PMID- 27274827 TI - Haematological malignancies and acute kidney injury requiring nephrology consultation: challenging the worst of the worst. AB - BACKGROUND: Acute kidney injury (AKI) often complicates the course of haematological malignancies (HMs) and confers a worse prognosis. The majority of these patients are managed by the attending physician, yet, a small group, mostly coincident with the worst presentation and outcomes, requires nephrology consultation, challenging the clinician with ethical issues regarding the decision to initiate or forgo renal support therapy. The purpose of this work is to identify the prognostic determinants for in-hospital mortality in this population. METHODS: A retrospective, observational chart review was undertaken at a single tertiary referral oncological centre. We reviewed the medical records of in-hospital patients with AKI and HM between 1 January 1995 and 31 December 2014 who met the criteria for RIFLE (Risk, Injury, and Failure; and Loss; and End stage kidney disease) classification of I or higher and were followed by a nephrologist. RESULTS: Three hundred and forty-five patients were included in the study. Predictors of in-hospital death in patients with HM and AKI were septic shock [odds ratio (OR) 4.290 (95% CI 2.058-8.943)], invasive mechanical ventilation (IMV) [OR 4.305 (95% CI 2.075-8.928)] and allogeneic stem cell transplantation (SCT) [OR 2.232 (95% CI 1.260-3.953)]. The combination of each risk factor was used to estimate the probability of dying. Patients with all three risk factors had a risk of death of 86%. CONCLUSIONS: Septic shock, IMV and allogeneic SCT were identified as independent predictors of death in patients with HM and AKI, with only a small chance of survival if all three were present. Depending on the combination of risk factors, the indication for aggressive life support therapies, such as RST, might be questionable. PMID- 27274828 TI - A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis. AB - A 40-year-old Japanese man who had a medical history of hypokalemic periodic paralysis 4 months prior was hospitalized to undergo a cholecystectomy. Hypokalemia, nephrocalcinosis and alkaluria suggesting distal renal tubular acidosis (dRTA) were detected, but metabolic acidosis was not evident. An ammonium chloride/furosemide-fludrocortisone/bicarbonate loading test demonstrated a remarkable disability in urinary H(+) excretion. A novel heterozygous mutation in the ATP6V0A4 gene encoding the vacuolar H(+)-ATPase (V ATPase) a4 subunit p.S544L was detected. Among cases of V-ATPase a4 mutations, this is the first case in which a heterozygous mutation developed to an incomplete or latent form of dRTA. PMID- 27274829 TI - Familial vasculitides: granulomatosis with polyangitis and microscopic polyangitis in two brothers with differing anti-neutrophil cytoplasm antibody specificity. AB - Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases. Although the aetiology of AAV is uncertain, it is likely that genetic and environmental factors contribute. We report the unusual case of two brothers presenting with AAV with differing clinical pictures and differing ANCA specificity. There is a recently identified difference in genetic risk factors associated with ANCA specificity, making it surprising that first degree relatives develop AAV with differing clinical and serological features. Our report illustrates the complex aetiology of AAV and suggests that further research on the interaction of genetic and environmental factors is needed. PMID- 27274830 TI - Incident chronic kidney disease: trends in management and outcomes. AB - BACKGROUND: Management trends in early chronic kidney disease (CKD) and their associations with clinical outcomes have not previously been reported. METHODS: We evaluated incident (Stage G3A) CKD patients from an integrated health care system in 2004-06, 2007-09 and 2010-12 to determine adjusted trends in screening (urinary protein quantification), treatment [prescription for angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and statin] and nephrology referral. For the same time periods, adjusted rates for mortality, progression to Stage G4 CKD and hospitalization for myocardial infarction or heart failure were calculated and compared across time periods. RESULTS: There were 728, 788 and 956 patients with incident CKD in 2004-06, 2007 09 and 2010-12, respectively. Adjusted rates of proteinuria quantification (31, 39 and 51 screens/100 person-years), statin prescription (53, 63 and 64 prescriptions/100 person-years) and nephrology referral (2, 3 and 5 referrals/100 person-years) all increased over time (P for trend <0.001 in all cases). ACEI/ARB prescription rates did not change (88, 83 and 80 prescriptions/100 person-years, P = 0.68). Adjusted death rates (7, 5 and 6 deaths/100 person-years), CKD progression (9, 10 and 7 progressors/100 person-years) and cardiovascular hospitalization (10, 8 and 9 hospitalizations per 100/person-years) did not change (P for trend >0.4 in all cases). CONCLUSION: In this integrated health care system, management of incident CKD over the past decade has intensified. PMID- 27274831 TI - High prevalence of chronic kidney disease in a semi-urban population of Western India. AB - BACKGROUND: Globally there is an increase in incidence of chronic kidney diseases (CKDs). Diabetes mellitus (DM), hypertension and stone diseases are the major risk factors for CKD. We organized kidney disease screening camps in a semi-urban population of Gujarat, India on the occasion of World Kidney Day (WKD). METHODS: Voluntary participants from six towns were screened. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula and CKD was defined as an eGFR <60 mL/min/1.73 m(2) or albuminuria >=1+. Urogenital ultrasonography was performed with emphasis on stone burden. Participants with known diabetes, stone diseases, hypertension, kidney/liver/cardiac disease, hepatitis, HIV, transplant recipients, pregnant women and those <18 years were excluded from the study. RESULTS: Of the 2350 participants (1438 men), CKD was found in 20.93% and eGFR <60 mL/min/1.73 m(2) was noted in 8.29% of participants. The prevalence of CKD peaked after the seventh decade of life in both genders. There was no significant difference in the prevalence of CKD between coastal and non-coastal regions, however, obesity, hypertension and diabetes were more common in the coastal belt, whereas stone burden was greater in the non-coastal region. CONCLUSIONS: The prevalence of CKD in a semi-urban apparently healthy Indian population was higher than the reported prevalence in developed countries. Significant differences between regions point to the need to evaluate and correctregion-specific risk factors. PMID- 27274833 TI - Diabetes mellitus as a cause of end-stage renal disease in Europe: signs of improvement. PMID- 27274832 TI - Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling. AB - BACKGROUND: In the setting of chronic kidney disease (CKD), altered extra-renal urate handling may be necessary to regulate plasma uric acid. The Remote Sensing and Signaling Hypothesis (Nigam S. What do drug transporters really do? Nat Rev Drug Discov 2015; 14: 29-44) suggests that multispecific solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters in different tissues are part of an inter-organ communication system that maintains levels of urate and other metabolites after organ injury. METHODS: Data from the Chronic Renal Insufficiency Cohort (CRIC; n = 3598) were used to study associations between serum uric acid and single nucleotide polymorphisms (SNPs) on the following uric acid transporters: ABCG2 (BRCP), SLC22A6 (OAT1), SLC22A8 (OAT3), SLC22A10 (OAT5), SLC22A11 (OAT4), SLC22A12 (URAT1), SLC22A13 (OAT10), SLC17A1-A3 (NPTs), SLC2A9 (GLUT9), ABCC2 (MRP2) and ABCC4 (MRP4). Regression models, controlling for principal components age, gender and renal function, were run separately for those of European (EA) and African ancestry (AA), and P-values corrected for multiple comparisons. A twin cohort with participants of EA and normal renal function was used for comparison. RESULTS: Among those of EA in CRIC, statistically significant signals were observed for SNPs in ABCG2 (rs4148157; beta-coefficient = 0.68; P = 4.78E-13) and SNPs in SLC2A9 (rs13125646; beta coefficient = -0.30; P = 1.06E-5). Among those of AA, the strongest (but not statistically significant) signals were observed for SNPs in SLC2A9, followed by SNPs in ABCG2. In the twin study (normal renal function), only SNPs in SLC2A9 were significant (rs4481233; beta-coefficient=-0.45; P = 7.0E-6). In CRIC, weaker associations were also found for SLC17A3 (NPT4) and gender-specific associations found for SLC22A8 (OAT3), SLC22A11 (OAT4), and ABCC4 (MRP4). CONCLUSIONS: In patients of EA with CKD (CRIC cohort), we found striking associations between uric acid and SNPs on ABCG2, a key transporter of uric acid by intestine. Compared with ABCG2, SLC2A9 played a much less significant role in this subset of patients with CKD. SNPs in other SLC (e.g. SLC22A8 or OAT3) and ABC (e.g. ABCC4 or MRP4) genes appear to make a weak gender-dependent contribution to uric acid homeostasis in CKD. As renal urate transport is affected in the setting of declining kidney function, extra-renal ABCG2 appears to play a compensatory role a notion consistent with animal studies and the Remote Sensing and Signaling Hypothesis. Overall, the data indicate how different urate transporters become more or less important depending on renal function, ethnicity and gender. Therapies focused on enhancing ABCG2 urate handling may be helpful in the setting of CKD and hyperuricemia. PMID- 27274835 TI - A study to describe the health trajectory of patients with advanced renal disease who choose not to receive dialysis. AB - BACKGROUND: Some patients with end-stage renal failure (ESRF) are unlikely to benefit from dialysis and conservative management (CM) is offered as a positive alternative. Understanding the trajectory of illness by health care professionals may improve end-of-life care. METHODS: We aimed to describe the trajectory of functional status within our CM population through a prospective, observational study using the objective Timed Up and Go (TUG) test and subjective Barthel Index (BI) and health-related quality of life (HRQoL) [EuroQol 5D-5L (EQ-5D-5L)] measurements and correlating them with demographic and laboratory data and with sentinel events. RESULTS: There was a significant increase in TUG scores over the 6 months prior to death {2.24 [95% confidence interval (CI) 1.16-4.32], P = 0.017} and a significant decrease in EQ-5D-5L [-0.19 (95% CI -0.33 to -0.06), P = 0.006]. The only significant associations with mortality were serum albumin [hazard ratio (HR) 0.81 (95% CI 0.67-0.97), P = 0.024] and male gender [HR 5.94 (95% CI 1.50-23.5), P = 0.011]. CONCLUSIONS: We have shown there is a significant decline in functional status in the last 6 months before death in the CM population. Of interest, there was a significant relationship of lower serum albumin with functional decline and risk of death. We hope that with improved insight into disease trajectories we can improve our ability to identify and respond to the changes in needs of these patients, facilitate complex and sensitive end-of-life discussions and improve end-of-life care. PMID- 27274836 TI - Comparison of Turkish and US haemodialysis patient mortality rates: an observational cohort study. AB - BACKGROUND: There are significant differences between countries in the mortality rates of haemodialysis (HD) patients. The extent of these differences and possible contributing factors are worthy of investigation. METHODS: As of March 2009, all patients undergoing HD or haemodiafiltration for >3 months (n = 4041) in the Turkish clinics of the NephroCare network were enrolled. Data were prospectively collected for 2 years through the European Clinical Dialysis Database. Mean age +/- standard deviation was 58.7 +/- 14.7 years, 45.9% were female and 22.9% were diabetic. Comparison with US data was performed by applying an indirect standardization technique, using specific mortality rates for patients on HD by age, gender, race and primary diagnosis as provided by the 2012 US Renal Data System Annual Data Report as reference. RESULTS: The crude mortality rate in Turkey was 95.1 per 1000 patient-years. Compared with the US reference population, the annual mortality rate for Turkey was significantly lower, irrespective of gender, age and diabetes. After adjustments for age, gender and diabetes, the mortality risk in the Turkish cohort was 50% lower than US whites [95% confidence interval (CI) 0.46-0.54, P < 0.001], 44% lower than US African-Americans (95% CI 0.52-0.61, P < 0.001) and 20% lower than Asian Americans (95% CI 0.74-0.86, P < 0.05). CONCLUSIONS: The annual mortality rate of prevalent HD patients was found to be significantly lower in the studied Turkish cohort compared with that published by the US Renal Data System Annual Data Report. Differences in practice patterns may contribute to the divergence. PMID- 27274837 TI - Sevelamer carbonate reduces the risk of hypomagnesemia in hemodialysis-requiring end-stage renal disease patients. AB - BACKGROUND: Sevelamer has been associated with less progression of vascular calcifications. This effect could be due to a reduction in serum phosphate levels but also to other additive effects. Magnesium has been also shown to prevent vascular calcification but the effect of sevelamer on serum magnesium levels has not been thoroughly evaluated. Our aim was to analyze whether the use of sevelamer reduces the risk of hypomagnesemia in hemodialysis (HD)-requiring end stage renal disease patients. METHODS: All prevalent patients from the dialysis unit of the Hospital Italiano de Buenos Aires as of 1 June 2015 were evaluated. They were on three times per week bicarbonate/citrate-buffered HD. They were not receiving phosphate binders or magnesium-containing drugs. The average of three successive monthly magnesium serum levels was considered as the baseline magnesium concentration. Sevelamer carbonate use was retrieved from the patient's clinical records. RESULTS: One hundred and fifty-one patients were included. A large proportion of individuals were on proton pump inhibitors (PPIs) (66%) and more than 50% were using sevelamer carbonate. Serum magnesium levels were significantly higher in those receiving sevelamer compared with those who did not (2.05 +/- 0.3 versus 1.8 +/- 0.4 mg/dL; P < 0.05). A larger proportion of individuals receiving sevelamer were among those with normal serum magnesium (P = 0.02), while among those with hypomagnesemia, a larger proportion were on PPIs. In the multivariate model including the use of PPIs, sevelamer carbonate resulted in an independent protective factor for hypomagnesemia (odds ratio: 0.44; 95% confidence interval: 0.21-0.87). CONCLUSIONS: Hemodialysis patients receiving sevelamer show higher serum magnesium levels and a reduced risk of hypomagnesemia. This effect remains even after adjustment for PPI use. This effect could contribute to the still controversial superiority of sevelamer in preventing vascular calcifications. PMID- 27274834 TI - Renal replacement therapy in Europe: a summary of the 2013 ERA-EDTA Registry Annual Report with a focus on diabetes mellitus. AB - BACKGROUND: This article provides a summary of the 2013 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era-edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). METHODS: In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient data were provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. RESULTS: In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013 was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp). When compared with the USA, the incidence of patients starting RRT pmp secondary to DM in Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5-61.3] and 50.6% (95% CI 49.9-51.2) for patients with DM as the cause of ESRD. PMID- 27274838 TI - Dialyzing women and men: does it matter? An observational study. AB - BACKGROUND: Application and consequences of hemodialysis treatment may differ between genders; focusing on these differences may be useful to optimize outcomes. METHODS: Data from 1 999 648 hemodialysis sessions performed in 10 984 (3316 incident and 7668 prevalent) patients, treated in 55 centers of the European Clinical Database (EuCliD)-Turkey, were analyzed, and various demographic, clinical, biochemical, therapeutic and prognostic parameters were compared. RESULTS: There were 1905 male and 1411 female incident and 4339 male and 3329 female prevalent patients. For females, the mean age in incident (61.8 +/- 14.9 years) and prevalent (58.3 +/- 15.2 years) patients was higher than for males (60.2 +/- 14.8 and 56.5 +/- 14.9 years, respectively) (P < 0.001 for both analyses). Also, body mass index was higher, while the hemoglobin level, and the percentage of interdialytic weight gain and arteriovenous fistula were lower. Serum phosphorus was similar in both genders in incident cases, while it was lower in prevalent female patients. Serum parathyroid hormone levels were lower in incident, but higher in prevalent male cases. Erythropoiesis-stimulating agents and vitamin D preparations were more frequently used in female incident and prevalent patients. Hospitalization was more frequent in prevalent females, while it did not differ significantly in the incident cases. Overall, no significant difference was observed in survival rates at 3 years in both incident and prevalent male and female patients. CONCLUSIONS: Many parameters differ significantly between female and male dialysis patients. Considering the effects of sex on several parameters may be a valuable approach for achieving better outcomes when formulating treatment strategies in this patient population. PMID- 27274839 TI - Patient's perceptions of chronic kidney disease and their association with psychosocial and clinical outcomes: a narrative review. AB - Patients with chronic kidney disease (CKD) form organized beliefs regarding their illness and treatment. These perceptions influence the coping strategies employed by an individual to manage his/her illness and may act as a predictor for his/her willingness to engage in self-management behaviours. While illness perceptions have been identified as predictors of non-adherence, depression and mortality in dialysis patients, there is a paucity of research in CKD patients not requiring renal replacement therapy. This narrative review synthesizes the existing literature regarding the role of illness perceptions and associated clinical and psychosocial outcomes in non-dialysis CKD patients. Studies were identified following database searches of AMED, BNI, CINAHL, EMBASE, Health Business Elite, HMIC, Medline, PsycINFO and Google Scholar in January 2016. Despite the small evidence base, existing studies indicate that negative illness perceptions are associated with disease progression and a number of psychosocial outcomes in non dialysis CKD patients. Evidence from other clinical populations suggests that illness perceptions are modifiable through psychological intervention, which may be most effective if delivered early before beliefs have the chance to become more established. Therefore, targeting illness perceptions in the earlier stages of CKD may be optimal. Further studies are now required to ascertain the mechanisms through which illness perceptions predict psychosocial and clinical outcomes in CKD patients and to ultimately test the efficacy of illness perception-based interventions. PMID- 27274840 TI - Differences in emotional responses in living and deceased donor kidney transplant patients. AB - BACKGROUND: The psychological functioning of living donor (LD) and deceased donor (DD) recipients are important factors for emotional adjustment to transplantation. This study investigated differences in medical, sociodemographic and emotional factors between these two groups. METHODS: A total of 241 kidney transplant recipients (68 LD, 173 DD) completed questionnaires on emotional and behavioural responses to transplantation, including quality of life, anxiety and depression, social support and experience with immunosuppressive medication. RESULTS: Overall, LD recipients were younger, better educated, more often employed and had a shorter duration of dialysis prior to transplantation. Findings indicate that LD recipients expressed more guilt towards the donor than DD recipients. In addition, more LD recipients experienced clinically significant levels of anxiety. Both groups experienced high levels of negative effects of immunosuppressant medication. No differences between LD and DD recipients were found for gender, relationship status, time since transplantation or transplant rejection treatment during the last 12 months. In addition, perceived social support and quality of life were comparable between the two groups. CONCLUSIONS: Feelings of guilt and anxiety may be an important focus for interventions to improve emotional adjustment to transplantation, especially in LD recipients. PMID- 27274841 TI - Caregiver word reading literacy and health outcomes among children treated in a pediatric nephrology practice. AB - BACKGROUND: Caregivers play a major role in the healthcare of pediatric patients, particularly during childhood and adolescence. This study examined the impact of caregivers' functional literacy on the health outcomes of adolescents with chronic kidney disease (CKD) or end-stage kidney disease (ESKD). METHODS: Caregiver-child dyads in a Southeastern US pediatric nephrology clinic participated in this cross-sectional study. We collected demographic information, data on caregivers' functional literacy skills (Wechsler Individual Achievement Test Word Reading Subtest) and child health outcomes (healthcare utilization and adherence). Negative binomial regression analyses were used to test the relationships. RESULTS: A total of 98 pediatric patients and their caregivers participated. Caregivers' word reading literacy was associated with their children's healthcare utilization. Patients whose caregivers had lower word reading literacy skills (<7th grade) had greater incidence of emergency room (ER) visits (adjusted incidence rate ratio = 2.05, 95% confidence interval: 1.007, 4.177, P < 0.05) after adjusting for major demographic factors. Patients' hospitalization rates and adherence to medication/diet/appointments were comparable in the two groups. CONCLUSIONS: Low caregiver functional word reading literacy was negatively related to health outcomes of adolescents with CKD/ESKD as reflected by greater ER visits. Educational materials and teaching strategies (dialysis training protocols, patient education materials) adjusted for low literacy levels may contribute to better outcomes. PMID- 27274843 TI - Resveratrol compares with melatonin in improving in vitro porcine oocyte maturation under heat stress. AB - BACKGROUND: Resveratrol, an important phyto-antioxidant commonly found in grapes, mulberry, and other plants, has a variety of functions including anti-aging, anti cancer and anti-inflammatory activities. In the current study, we investigated the beneficial effects of resveratrol on in vitro porcine oocyte maturation under heat stress (HS). The effect of resveratrol, melatonin and their combination on alleviating HS was compared according to the maturation rate of oocytes and the development competence of embryos after parthenogenetic activation (PA). RESULTS: Supplementation with resveratrol (2.0 MUmol/L) not only improved the nuclear maturation but also raised the blastocyst rate of porcine embryos' PA from oocytes that underwent HS by increasing their glutathione (GSH) level, reducing reactive oxygen species (ROS) and up-regulating the expression of Sirtuin 1 (SIRT1). It was also found that melatonin (10(-7) mol/L) and the combination of resveratrol (2.0 MUmol/L) plus melatonin (10(-7) mol/L) exhibited more potent effects than resveratrol alone regarding their protective activities on oocyte maturation under HS. CONCLUSIONS: This study compared the efficiencies of resveratrol, melatonin and their combination for protecting porcine oocytes from heat stress. The mechanisms are attributed to the fact that each treatment may have different ability to regulate the synthesis of steroid hormones and the expression of mature related genes. PMID- 27274842 TI - Improving clinical skills to support the emotional and psychological well-being of patients with end-stage renal disease: a qualitative evaluation of two interventions. AB - BACKGROUND: Many patients with end-stage renal disease (ESRD) need and want improved emotional and psychological support. Explicit attention to patients' emotional issues during consultations can help, yet renal consultants rarely address emotional problems. This qualitative study aimed to evaluate whether two different low-cost interventions could individually enable consultants to talk with patients about their emotional concerns during routine outpatient consultations. METHOD: One intervention involved patients using a Patient Issues Sheet to identify two to three issues they would like to talk about in their consultation and the second involved consultants asking patients a direct question about their emotional feelings. Consultants were trained to handle any emotional issues raised. Semi-structured interviews were conducted with five consultants and 36 ESRD patients from two UK renal units. Interviews were transcribed verbatim and analysed using the constant comparative method. RESULTS: Although consultants and patients tended to use the two interventions in different ways, they expressed generally positive views about how helpful the interventions were in promoting discussion of emotional issues. Consultants appreciated the training for facilitating empathetic handling of patients' emotional disclosures and containment of discussion. Most patients who raised emotional concerns were satisfied with their consultant's responses, while others were dissuaded from more explicit discussion by their consultant's concentration on physical considerations. CONCLUSIONS: These qualitative study findings suggest that both interventions are feasible and acceptable and have the potential to help consultants improve emotional and psychological patient care, providing cognitive and behavioural tools to enable discussion of emotional issues during routine outpatient consultations. PMID- 27274844 TI - Modification of TiO2 by Bimetallic Au-Cu Nanoparticles for Wastewater Treatment. AB - Au, Cu and bimetallic Au-Cu nanoparticles were synthesized on the surface of commercial TiO2 compounds (P25) by reduction of the metal precursors with tetrakis (hydroxymethyl) phosphonium chloride (THPC) (0.5 % in weight). The alloyed structure of Au-Cu NPs was confirmed by HAADF-STEM, EDS, HRTEM and XPS techniques. The photocatalytic properties of the modified TiO2 have been studied for phenol photodegradation in aqueous suspensions under UV-visible irradiation. The modification by the metal nanoparticles induces an increase in the photocatalytic activity. The highest photocatalytic activity is obtained with Au Cu/TiO2 (Au/Cu 1:3). Their electronic properties have been studied by time resolved microwave conductivity (TRMC) to follow the charge-carrier dynamics. TRMC measurements show that the TiO2 modification with Au, Cu and Au-Cu nanoparticles plays a role in charge-carrier separations increasing the activity under UV-light. Indeed, the metal nanoparticles act as a sink for electron, decreasing the charge carrier recombination. The TRMC measurements show also that the bimetallic Au-Cu nanoparticles are more efficient in electron scavenging than the monometallic Au and Cu ones. PMID- 27274845 TI - Pituitary abscess: a case report and review of the literature. AB - Pituitary abscess is a rare life-threating entity that is usually misdiagnosed as a pituitary tumor with a definite diagnosis only made postoperatively. Over the last several decades, advances in healthcare have led to a significant decrease in morbidity and mortality due to pituitary abscess. We report a case of a 34 year-old woman who was admitted to our department for investigation of a pituitary mass and with symptoms of pituitary dysfunction, headaches and impaired vision. During her admission, she developed meningitis-like symptoms and was treated with antibiotics. She eventually underwent transsphenoidal surgery for excision of the pituitary mass. A significant amount of pus was evident intraoperatively; however, no pathogen was isolated. Six months later, the patient was well and had full recovery of the anterior pituitary function. Her menses returned, and she was only on treatment with desmopressin for diabetes insipidus that developed postoperatively. LEARNING POINTS: Pituitary abscess is a rare disease and the reported clinical features vary mimicking other pituitary lesions.The diagnosis of pituitary abscess is often very difficult to make and rarely included in the differential.The histological findings of acute inflammatory infiltration confirm the diagnosis of pituitary abscess.Medical and surgical treatment is usually recommended upon diagnosis of a pituitary abscess. PMID- 27274846 TI - Challenges in achieving a target international normalized ratio for deep vein thrombosis among HIV-infected patients with tuberculosis: a case series. AB - BACKGROUND: Tuberculosis (TB) and HIV are among the risk factors for deep vein thrombosis (DVT). There are several challenges in the management of DVT patients with TB-HIV co-infection including drug-drug interactions and non-adherence due to pill burden. METHODS: HIV infected patients starting treatment for TB were identified and followed up two weekly. Cases of DVT were diagnosed with Doppler ultrasound and patients were initiated on oral anticoagulation with warfarin and followed up with repeated INR measurements and warfarin dose adjustment. RESULTS: We describe 7 cases of TB and HIV-infected patients in Uganda diagnosed with DVT and started on anticoagulation therapy. Their median age was 30 (IQR: 27-39) years and 86 % were male. All patients had co-medication with cotrimoxazole, tenofovir, lamivudine and efavirenz and some were on fluconazole. The therapeutic range of the International Normalization Ratio (INR) was difficult to attain and unpredictable with some patients being under-anticoagulated and others over anticoagulated. The mean Time in Therapeutic Range (TTR) for patients who had all scheduled INR measurements in the first 12 weeks was 33.3 %. Only one patient among those with all the scheduled INR measurements had achieved a therapeutic INR by 2 weeks. Four out of seven (57 %) of the patients had at least one INR above the therapeutic range which required treatment interruption. None of the patients had major bleeding. CONCLUSION: We recommend more frequent monitoring and timely dose adjustment of the INR, as well as studies on alternative strategies for the treatment of DVT in TB-HIV co-infected patients. PMID- 27274847 TI - A systematic review of financial incentives given in the healthcare setting; do they effectively improve physical activity levels? AB - BACKGROUND: According to current physical activity guidelines, a substantial percentage of the population in high-income countries is inactive, and inactivity is an important risk factor for chronic conditions and mortality. Financial incentives may encourage people to become more active. The objective of this review was to provide insight in the effectiveness of financial incentives used for promoting physical activity in the healthcare setting. METHODS: A systematic literature search was performed in three databases: Medline, EMBASE and SciSearch. In total, 1395 papers published up until April 2015 were identified. Eleven of them were screened on in- and exclusion criteria based on the full-text publication. RESULTS: Three studies were included in the review. Two studies combined a financial incentive with nutrition classes or motivational interviewing. One of these provided a free membership to a sports facility and the other one provided vouchers for one episode of aerobic activities at a local leisure center or swimming pool. The third study provided a schedule for exercise sessions. None of the studies addressed the preferences of their target population with regard to financial incentives. Despite some short-term effects, neither of the studies showed significant long-term effects of the financial incentive. CONCLUSIONS: Based on the limited number of studies and the diversity in findings, no solid conclusion can be drawn regarding the effectiveness of financial incentives on physical activity in the healthcare setting. Therefore, there is a need for more research on the effectiveness of financial incentives in changing physical activity behavior in this setting. There is possibly something to be gained by studying the preferred type and size of the financial incentive. PMID- 27274848 TI - Pre-pubertal males practising Taekwondo exhibit favourable postural and neuromuscular performance. AB - BACKGROUND: The postural and neuromuscular performances in healthy children taekwondo (TKD) practitioners in comparison with control children were examined. METHODS: Seventeen healthy pre-pubertal males undertaking only physical education at school (age: 11.88 +/- 0.33 years) and 12 pre-pubertal male TKD practitioners (>3 years, 4 sessions a week) (age 11.66 +/- 0.49 years) were recruited. Performances in the dynamic postural control (Star Excursion Balance Test -SEBT), vertical jump [squat jump (SJ) and countermovement jump (CMJ)] and sprint running (distances: 5, 10, 20 and 30 m) tests were compared between the two groups. RESULTS: The performances of the TKD practitioners were better than those of the non-TKD active for the SEBT (for 14 of 16 conditions, p < 0.05), SJ (p < 0.01), CMJ (p < 0.03) sprint running (5 m, p < 0.01; 10 m, p < 0.04; the performances for the 20 and 30 m sprints were not significant, p > 0.05). CONCLUSIONS: TKD practice would stimulate sensory input and motor output of the postural system that would enhance its efficiency. In addition, the dynamic nature of TKD would develop the muscle power of the lower limbs. In our sample of healthy pre pubertal males, TKD appears to improve postural and neuromuscular functions, but further research is required. PMID- 27274849 TI - Complete coding sequence of Zika virus from Martinique outbreak in 2015. AB - Zika virus is an Aedes-borne Flavivirus causing fever, arthralgia, myalgia rash, associated with Guillain-Barre syndrome and suspected to induce microcephaly in the fetus. We report here the complete coding sequence of the first characterized Caribbean Zika virus strain, isolated from a patient from Martinique in December, 2015. PMID- 27274850 TI - First genome sequences of buffalo coronavirus from water buffaloes in Bangladesh. AB - We report the complete genome sequences of a buffalo coronavirus (BufCoV HKU26) detected from the faecal samples of two domestic water buffaloes (Bubalus bubalis) in Bangladesh. They possessed 98-99% nucleotide identities to bovine coronavirus (BCoV) genomes, supporting BufCoV HKU26 as a member of Betacoronavirus 1. Nevertheless, BufCoV HKU26 possessed distinct accessory proteins between spike and envelope compared to BCoV. Sugar-binding residues in the N-terminal domain of S protein in BCoV are conserved in BufCoV HKU26. PMID- 27274851 TI - Linezolid-resistant mucoid Staphylococcus haemolyticus from a tertiary-care centre in Delhi. AB - We report an unusual morphological mucoid variant of Staphylococcus haemolyticus associated with linezolid resistance from a patient with sepsis. Linezolid resistance and mucoid character together made this pathogen difficult to treat. To our knowledge this is the first such report. PMID- 27274852 TI - Polydrug abuse associated with nitrous oxide causes death. PMID- 27274853 TI - Cefepime-induced encephalopathy with normal renal function. AB - Cefepime is a fourth-generation cephalosporin that is frequently used in a wide array of infections. Since approval for use, concerns have been raised due to adverse effects including seizures, encephalopathy and myoclonus especially if renal dysfunction is present. Despite having appropriate renal dose adjustments, cases have been found with adverse neurological effects. On this occasion, we present a case of a patient with normal renal function that had demonstrated cefepime-induced encephalopathy with full resolution of symptoms following discontinuation of the medication. PMID- 27274854 TI - Dengue fever complicated by hemophagocytosis. AB - Dengue is a common acute viral febrile illness in the tropics. Although the usual presentation is that of a self-limiting illness, its complications are protean. We report a 29-year-old man who presented with an acute febrile illness and was diagnosed with dengue hemorrhagic fever. Despite appropriate supportive therapy, the patient initially improved, but subsequently had clinical deterioration. Evaluation revealed features of hemophagocytic lymphohistiocytosis. He was successfully treated with glucocorticoids and had an uneventful recovery. This case adds to the limited adult cases of virus-associated hemophagocytic syndrome in the literature and the need for prompt recognition and treatment of this rare complication. PMID- 27274855 TI - Competing interests in a lung cancer with metastasis to the pituitary gland: syndrome of inappropriate ADH secretion versus diabetes insipidus. AB - Metastases to the pituitary gland are rare; cancers that most commonly metastasize to the pituitary are breast and lung cancers. No specific computed tomography or magnetic resonance imaging features reliably distinguish primary pituitary masses from metastases. A combination of a detailed clinical assessment together with specialist endocrine and neuroradiology support is essential to make the rare diagnosis of a pituitary metastasis. We present the case of a man with metastatic lung cancer, initially presenting as hypopituitarism. Subtle features in the history, together with neuroimaging findings atypical for pituitary adenomas, provided clues that the diagnosis was one of the pituitary metastases. Treatment of diabetes insipidus (DI) with replacement antidiuretic hormone (ADH) was complicated by extreme difficulties in achieving a satisfactory sodium and water balance. This was the result of coexistent DI and syndrome of inappropriate ADH secretion perpetuated by the patient's primary lung cancer, a phenomenon not previously described in the literature. PMID- 27274856 TI - Saddle pulmonary embolism: right ventricular strain an indicator for early surgical approach. AB - Current mainstay treatment for pulmonary embolism (PE) includes oral anticoagulation, thrombolytic therapy, catheter embolectomy and acute surgical embolectomy. Surgical embolectomy is reserved for hemodynamically unstable patients (cardiogenic shock, cardiac arrest) and contraindication to thrombolytic therapy. We report a case of saddle PE in a young female with echocardiographic signs of right ventricular (RV) dysfunction who underwent early acute surgical embolectomy with a positive outcome. It would be beneficial to use bedside echocardiography even in hemodynamically stable patients to determine RV strain as this could act as an early indicator suggesting the escalation of therapy. PMID- 27274858 TI - A novel type II collagen gene mutation in a family with spondyloepiphyseal dysplasia and extensive intrafamilial phenotypic diversity. AB - The purpose of this study was to describe a family with spondyloepiphyseal dysplasia caused by a novel type II collagen gene (COL2A1) mutation and the family's phenotypic diversity. Clinical and radiographic examinations of skeletal dysplasia were conducted on seven affected family members across two generations. The entire coding region of COL2A1, including the flanking intron regions, was analyzed with PCR and direct sequencing. The stature of the subjects ranged from extremely short to within normal height range. Hip deformity and advanced osteoarthritis were noted in all the subjects, ranging from severe coxa plana to mild acetabular dysplasia. Atlantoaxial subluxation combined with a hypoplastic odontoid process was found in three of the subjects. Various degrees of platyspondyly were confirmed in all subjects. Genetically, a novel COL2A1 mutation (c.1349G>C, p.Gly450Ala) was identified in all the affected family members; however, it was not present in the one unaffected family member tested. We described a family with spondyloepiphyseal dysplasia and a novel COL2A1 mutation (c.1349G>C, p.Gly450Ala). Phenotypes were diverse even among individuals with the same mutation and within the same family. PMID- 27274857 TI - A catalog of hemizygous variation in 127 22q11 deletion patients. AB - The 22q11.2 deletion syndrome is the most common microdeletion disorder, with wide phenotypic variability. To investigate variation within the non-deleted allele we performed targeted resequencing of the 22q11.2 region for 127 patients, identifying multiple deletion sizes, including two deletions with atypical breakpoints. We cataloged ~12,000 hemizygous variant positions, of which 84% were previously annotated. Within the coding regions 95 non-synonymous variants, three stop gains, and two frameshift insertions were identified, some of which we speculate could contribute to atypical phenotypes. We also catalog tolerability of 22q11 gene mutations based on related autosomal recessive disorders in man, embryonic lethality in mice, cross-species conservation and observations that some genes harbor more or less variants than expected. This extensive catalog of hemizygous variants will serve as a blueprint for future experiments to correlate 22q11DS variation with phenotype. PMID- 27274859 TI - A de novo microdeletion in a patient with inner ear abnormalities suggests that the 10q26.13 region contains the responsible gene. AB - Microdeletions in the 10q26.1 region are related to intellectual disability, growth delay, microcephaly, distinctive craniofacial features, cardiac defects, genital abnormalities and inner ear abnormalities. The genes responsible for inner ear abnormalities have been narrowed to fibroblast growth factor receptor 2 gene (FGFR2), H6 family homeobox 2 gene (HMX2) and H6 family homeobox 3 gene (HMX3). An additional patient with distinctive craniofacial features, congenital deafness and balance dysfunctions showed a de novo microdeletion of 10q26.11q26.13, indicating the existence of a gene responsible for inner ear abnormalities in this region. PMID- 27274860 TI - Novel OPN1LW/OPN1MW deletion mutations in 2 Japanese families with blue cone monochromacy. AB - Blue cone monochromacy (BCM) is caused by the lack of expression of the normal proteins encoded by the OPN1LW and OPN1MW genes, resulting in the absence of red and green cone sensitivities. We analyzed two cases of BCM in two different families and identified deletion mutations in the locus control region upstream of the two genes. Deletion breakpoints were determined to an accuracy of one base for both cases. PMID- 27274861 TI - Physical, morphological, and wound healing properties of a polyurethane foam-film dressing. AB - BACKGROUND: We investigated the physicochemical properties of Medifoam(r) N and its wound healing performance compared to other commercially available polyurethane (PU) foam dressing in vitro and in vivo to gain insight in their clinical performance. METHODS: Wound contact layer and cross-section of eleven polyurethane foam dressings were assessed with field-emission scanning electron microscope. Thickness, density, tensile strength, elongation, moisture-vapor transmission rate (MVTR), retention and absorptivity were measured to compare physical properties. Phosphate-buffered saline (PBS) solution absorption patterns were compared. An animal model for wound-healing was applied to validate in vitro findings. RESULTS: Among eleven tested foam dressings, Medifoam(r) N has the smallest pore and cell sizes with excellent uniformity, i.e. it has 25 ~ 75 MUm on the wound contact layer and 100 ~ 350 MUm in the cross-section while other dressings have a larger pose size with larger variability. Compared to other PU foams, Medifoam(r) N also has moderate thickness, density, tensile strength, elongation and MVTR. Furthermore, it has excellent fluid absorption and retention capacity. These intrinsic properties of Medifoam(r) N contributed to improve fluid absorption patterns, i.e. other dressing material flawed out PBS solution on the dressings while Medifoam(r) N retained all the tested solutions. In animal wound-healing study, Medifoam(r) N treated animals showed excellent angiogenesis and collagen deposition even though epithelial recovery rate was not significantly different to other dressings. CONCLUSIONS: Medifoam(r) N has optimized physical properties and thus improved fluid absorption/retention capacity. Compared to other dressings, Medifoam(r) N showed excellent fluid absorption patterns and these characteristics contributed to improved wound healing and excellent angiogenic potential. We found that Medifoam(r) N showed the best results among the employed dressing samples. PMID- 27274863 TI - Fast range measurement of spot scanning proton beams using a volumetric liquid scintillator detector. AB - Accurate confirmation and verification of the range of spot scanning proton beams is crucial for correct dose delivery. Current methods to measure proton beam range using ionization chambers are either time-consuming or result in measurements with poor spatial resolution. The large-volume liquid scintillator detector allows real-time measurements of the entire dose profile of a spot scanning proton beam. Thus, liquid scintillator detectors are an ideal tool for measuring the proton beam range for commissioning and quality assurance. However, optical artefacts may decrease the accuracy of measuring the proton beam range within the scintillator tank. The purpose of the current study was to 1) develop a geometric calibration system to accurately calculate physical distances within the liquid scintillator detector, taking into account optical artefacts; and 2) assess the accuracy, consistency, and robustness of proton beam range measurement using the liquid scintillator detector with our geometric calibration system. The range of the proton beam was measured with the calibrated liquid scintillator system and was compared to the nominal range. Measurements were made on three different days to evaluate the setup robustness from day to day, and three sets of measurements were made for each day to evaluate the consistency from delivery to delivery. All proton beam ranges measured using the liquid scintillator system were within half a millimeter of the nominal range. The delivery-to-delivery standard deviation of the range measurement was 0.04 mm, and the day-to-day standard deviation was 0.10 mm. In addition to the accuracy and robustness demonstrated by these results when our geometric calibration system was used, the liquid scintillator system allowed the range of all 94 proton beams to be measured in just two deliveries, making the liquid scintillator detector a perfect tool for range measurement of spot scanning proton beams. PMID- 27274862 TI - Uncovering low-dimensional, miR-based signatures of acute myeloid and lymphoblastic leukemias with a machine-learning-driven network approach. AB - Complex phenotypic differences among different acute leukemias cannot be fully captured by analyzing the expression levels of one single molecule, such as a miR, at a time, but requires systematic analysis of large sets of miRs. While a popular approach for analysis of such datasets is principal component analysis (PCA), this method is not designed to optimally discriminate different phenotypes. Moreover, PCA and other low-dimensional representation methods yield linear or non-linear combinations of all measured miRs. Global human miR expression was measured in AML, B-ALL, and TALL cell lines and patient RNA samples. By systematically applying support vector machines to all measured miRs taken in dyad and triad groups, we built miR networks using cell line data and validated our findings with primary patient samples. All the coordinately transcribed members of the miR-23a cluster (which includes also miR-24 and miR 27a), known to function as tumor suppressors of acute leukemias, appeared in the AML, B-ALL and T-ALL centric networks. Subsequent qRT-PCR analysis showed that the most connected miR in the B-ALL-centric network, miR-708, is highly and specifically expressed in B-ALLs, suggesting that miR-708 might serve as a biomarker for B-ALL. This approach is systematic, quantitative, scalable, and unbiased. Rather than a single signature, our approach yields a network of signatures reflecting the redundant nature of biological signaling pathways. The network representation allows for visual analysis of all signatures by an expert and for future integration of additional information. Furthermore, each signature involves only small sets of miRs, such as dyads and triads, which are well suited for in depth validation through laboratory experiments. In particular, loss-and gain-of-function assays designed to drive changes in leukemia cell survival, proliferation and differentiation will benefit from the identification of multi miR signatures that characterize leukemia subtypes and their normal counterpart cells of origin. PMID- 27274864 TI - The role of the priming loop in Influenza A virus RNA synthesis. AB - RNA-dependent RNA polymerases (RdRps) are used by RNA viruses to replicate and transcribe their RNA genomes1. They adopt a closed, right-handed fold with conserved subdomains called palm, fingers, and thumb1,2. Conserved RdRp motifs A F coordinate the viral RNA template, NTPs, and magnesium ions to facilitate nucleotide condensation1. For the initiation of RNA synthesis, most RdRps use either a primer-dependent or de novo mechanism3. The Influenza A virus RdRp in contrast, uses a capped RNA oligonucleotide to initiate transcription, and a combination of terminal and internal de novo initiation for replication4. To understand how the Influenza A virus RdRp coordinates these processes, we analysed the function of a thumb subdomain beta-hairpin using initiation, elongation, and single-molecule FRET assays. Our data shows that this beta hairpin is essential for terminal initiation during replication, but auxiliary for internal initiation and transcription. Analysis of individual residues in the tip of the beta-hairpin shows that PB1 proline 651 is critical for efficient RNA synthesis in vitro and in cell culture. Overall, this work advances our understanding of Influenza A virus RNA synthesis and identifies the initiation platform of viral replication. PMID- 27274865 TI - Retinal Ganglion Cell Atrophy in Homonymous Hemianopia due to Acquired Occipital Lesions Observed Using Cirrus High-Definition-OCT. AB - Purpose. To report a reduction in macular ganglion cell layer and inner plexiform layer (GCL+IPL) thickness and circumpapillary retinal nerve fiber layer (cpRNFL) thickness using spectral-domain optical coherence tomography in patients with homonymous hemianopia due to posterior cerebral artery (PCA) stroke. Methods. Seven patients with PCA stroke were examined using Cirrus high-definition-OCT. The GCL+IPL thicknesses were divided into the hemianopic and unaffected sides. The relationship between the time after stroke and the GCL+IPL thicknesses in the hemianopic side was evaluated. Results. The average thicknesses of the GCL+IPL were 64.6 and 82.0 MUm on the hemianopic and unaffected sides, respectively, and the measurement was significantly thinner on the former side (p = 0.018). A regression analysis revealed a negative linear relationship (R (2) = 0.574, p = 0.049) between the time after stoke and the GCL+IPL thicknesses on the hemianopic side. The supratemporal and inferotemporal cpRNFL thicknesses in the eyes ipsilateral to the stroke showed a significant reduction. Conclusion. Our findings confirmed our previous observations that the degeneration of retinal ganglion cells can occur after PCA stroke. GCL+IPL thinning was demonstrated in the hemiretinae corresponding to the affected hemifields. Also, it is suggested that the retinal changes observed are progressive. PMID- 27274866 TI - Daily Optical Coherence Tomography Examinations after First Antivascular Endothelial Growth Factor Injections: An Interventional Case Series. AB - Purpose. To evaluate daily spectral-domain optical coherence tomography (SD-OCT) changes in naive-treatment patients with diagnosis of exudative age-related macular degeneration (AMD) treated with intravitreous bevacizumab (1.25 mg), during a 30-day follow-up period. Methods. In prospective, interventional study, SD-OCT was performed daily for 30 days after the first intravitreal injection. The baseline, initial-decrease, minimal, and final central retinal thicknesses (CRTs) were assessed. Results. Nine eyes of nine patients with neovascular AMD were enrolled. The mean baseline CRT was 625.3 +/- 182.5 MUm, and the mean final CRT was 383.4 +/- 163.0 MUm (mean difference, 206.1 +/- 167.6 MUm), a difference that reached significance (P = 0.006). After the first injection, the initial decrease in the CRT was seen as an average of one day after injection (mean CRT, 503.6 +/- 189.10 MUm; P = 0.0431). The speed of the reduction in the CRT tended to decrease by day 17. The mean CRT was 336.5 +/- 105.44 MUm and the mean minimal CRT on day 30 was 320.75 +/- 96.38 MUm. Conclusion. The CRT decreased early after the first injection. We observed a tendency for reductions in the speed with which the CRT decreased by day 17 after the first injection, which may affect retreatment regime. PMID- 27274867 TI - Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia. AB - High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whether the postprandial DMAA profiles are associated with fasting glycaemia. We used a crossover design with twenty-one healthy individuals and four different isocaloric test meals, containing proteins from different dietary sources (dairy, fish, meat, and plants). Analysis of the postprandial DMAAs concentrations was performed using targeted mass spectrometry. A DMAA score was defined as the sum of all the three amino acid concentrations. The postprandial area under the curve (AUC) of all the three amino acids and the DMAA score was significantly greater after intake of the meal with dairy protein compared to intake of the three other meals. The postprandial AUC for the DMAA score and all the three amino acids strongly associated with fasting glucose level and insulin resistance. This indicates the importance of the postprandial kinetics and metabolism of DMAAs in understanding the overall association between DMAAs and glycaemia. PMID- 27274868 TI - Salivary Myeloperoxidase, Assessed by 3,3'-Diaminobenzidine Colorimetry, Can Differentiate Periodontal Patients from Nonperiodontal Subjects. AB - Periodontal diseases, which result from inflammation of tooth supporting tissues, are highly prevalent worldwide. Myeloperoxidase (MPO), from certain white blood cells in saliva, is a biomarker for inflammation. We report our study on the salivary MPO activity and its association with severity of periodontal diseases among Thai patients. Periodontally healthy subjects (n = 11) and gingivitis (n = 32) and periodontitis patients (n = 19) were enrolled. Assessments of clinically periodontal parameters were reported as percentages for gingival bleeding index (GI) and bleeding on probing (BOP), whereas pocket depth (PD) and clinical attachment loss (CAL) were measured in millimeters and then made to index scores. Salivary MPO activity was measured by colorimetry using 3,3'-diaminobenzidine as substrate. The results showed that salivary MPO activity in periodontitis patients was significantly higher than in healthy subjects (p = 0.003) and higher than in gingivitis patients (p = 0.059). No difference was found between gingivitis and healthy groups (p = 0.181). Significant correlations were observed (p < 0.01) between salivary MPO activity and GI (r = 0.632, p < 0.001), BOP (r = 0.599, p < 0.001), PD (r = 0.179, p = 0.164), and CAL (r = 0.357, p = 0.004) index scores. Sensitivity (94.12%), specificity (54.55%), and positive (90.57%) and negative (66.67%) predictive values indicate that salivary MPO activity has potential use as a screening marker for oral health of the Thai community. PMID- 27274869 TI - Obesity May Be Protective against Severe Perineal Lacerations. AB - Objective. To determine if there is an association between BMI and 3rd- or 4th degree perineal lacerations in normal spontaneous and operative vaginal deliveries. Study Design. We performed a retrospective case control study using a large obstetric quality improvement database over a six-year period. Cases were identified as singleton gestations with third- and fourth-degree lacerations. Controls were obtained randomly from the database of patients without third- or fourth-degree lacerations in a 1 : 1 ratio. Univariate and multivariate logistic regression analyses were performed. Results. Of 32,607 deliveries, 22,011 (67.5%) charts with BMI documented were identified. Third- or fourth-degree lacerations occurred in 2.74% (n = 605) of patients. 37% (n = 223) were identified in operative vaginal deliveries. In the univariate analysis, obesity, older maternal age, non-Asian race, and birth weight <4000 g were all protective against 3rd- and 4th-degree lacerations. After controlling for age, race, mode of vaginal delivery, and birth weight, obesity remained significant. Conclusion. Being obese may protect against third- and fourth-degree lacerations independent of parity, race, birth weight, and mode of delivery. PMID- 27274870 TI - Active Holistic Surveillance: The Nutritional Aspect of Delayed Intervention in Prostate Cancer. AB - Purpose. Active surveillance is an emergent strategy for management of indolent prostate cancer. Our institution's watchful waiting protocol, Active Holistic Surveillance (AHS), implements close monitoring for disease progression along with various chemopreventive agents and attempts to reduce unnecessary biopsies. Our objective is to report on the treatment rates of men on our AHS protocol as well as determine reasons for progression. Materials/Methods. Low risk and low intermediate risk patients were enrolled in AHS at Winthrop University Hospital between February 2002 and August 2015. Our IRB-approved study analyzed survival rate, discontinuation rates, and definitive treatments for patients in our AHS cohort. Results. 235 patients met inclusion criteria. Median age and follow-up for the cohort were 66 (44-88) years and 42 (3-166) months, respectively. The overall survival for the cohort was 99.6% and the disease specific survival was 100%. A total of 27 (11.5%) patients discontinued AHS. Conclusion. The incorporation of chemopreventive agents in our AHS protocol has allowed patients to prolong definitive treatment for many years. Longer follow-up and additional studies are necessary to further validate the effectiveness of AHS. PMID- 27274871 TI - Retracted: Is Hippocampus Susceptible to Antinociceptive Tolerance to NSAIDs Like the Periaqueductal Grey? AB - [This retracts the article DOI: 10.1155/2014/654578.]. PMID- 27274872 TI - Exploring Self-Efficacy in Australian General Practitioners Managing Patient Obesity: A Qualitative Survey Study. AB - Background. Obesity is a leading cause of morbidity and mortality in the Australian community, and general practitioners (GPs) are commonly approached by patients for assistance in losing weight. Previous studies have shown that GPs have low self-efficacy and low outcome expectation when it comes to managing overweight and obese patients, which affects their willingness to initiate and continue with weight counselling. This qualitative survey study aimed to explore the factors influencing confidence and behaviour in obesity management in GPs. Method. Twelve GPs recruited to deliver a pilot of an obesity management program participated in semistructured interviews, and interpretive analysis underpinned by social cognitive theory was performed on the transcripts. Results. Analysis identified five main themes: (1) perceived knowledge and skills, (2) structure to management approach, (3) the GP-patient relationship, (4) acknowledged barriers to weight loss and lifestyle change, and (5) prior experience and outcome expectation. Conclusions. GPs are likely to welcome tools which provide a more structured approach to obesity management. Shifting away from weight and BMI as sole yardsticks for success or failure and emphasising positive lifestyle changes for their own sake may improve GP self-efficacy and allow for a more authentic GP patient interaction. PMID- 27274873 TI - Astrocyte Hypertrophy Contributes to Aberrant Neurogenesis after Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is a widespread epidemic with severe cognitive, affective, and behavioral consequences. TBIs typically result in a relatively rapid inflammatory and neuroinflammatory response. A major component of the neuroinflammatory response is astrocytes, a type of glial cell in the brain. Astrocytes are important in maintaining the integrity of neuronal functioning, and it is possible that astrocyte hypertrophy after TBIs might contribute to pathogenesis. The hippocampus is a unique brain region, because neurogenesis persists in adults. Accumulating evidence supports the functional importance of these newborn neurons and their associated astrocytes. Alterations to either of these cell types can influence neuronal functioning. To determine if hypertrophied astrocytes might negatively influence immature neurons in the dentate gyrus, astrocyte and newborn neurons were analyzed at 30 days following a TBI in mice. The results demonstrate a loss of radial glial-like processes extending through the granule cell layer after TBI, as well as ectopic growth and migration of immature dentate neurons. The results further show newborn neurons in close association with hypertrophied astrocytes, suggesting a role for the astrocytes in aberrant neurogenesis. Future studies are needed to determine the functional significance of these alterations to the astrocyte/immature neurons after TBI. PMID- 27274874 TI - Increase in Growth Cone Size Correlates with Decrease in Neurite Growth Rate. AB - Several important discoveries in growth cone cell biology were made possible by the use of growth cones derived from cultured Aplysia bag cell neurons, including the characterization of the organization and dynamics of the cytoskeleton. The majority of these Aplysia studies focused on large growth cones induced by poly-L lysine substrates at early stages in cell culture. Under these conditions, the growth cones are in a steady state with very little net advancement. Here, we offer a comprehensive cellular analysis of the motile behavior of Aplysia growth cones in culture beyond this pausing state. We found that average growth cone size decreased with cell culture time whereas average growth rate increased. This inverse correlation of growth rate and growth cone size was due to the occurrence of large growth cones with a peripheral domain larger than 100 MUm(2). The large pausing growth cones had central domains that were less consistently aligned with the direction of growth and could be converted into smaller, faster-growing growth cones by addition of a three-dimensional collagen gel. We conclude that the significant lateral expansion of lamellipodia and filopodia as observed during these culture conditions has a negative effect on neurite growth. PMID- 27274876 TI - Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis. AB - Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions. PMID- 27274875 TI - Early Social Enrichment Improves Social Motivation and Skills in a Monogenic Mouse Model of Autism, the Oprm1 (-/-) Mouse. AB - Environmental enrichment has been proven to have positive effects on both behavioral and physiological phenotypes in rodent models of mental and neurodevelopmental disorders. In this study, we used mice lacking the u-opioid receptor gene (Oprm1 (-/-)), which has been shown to have deficits in social competence and communication, to assess the hypothesis that early enrichment can ameliorate sociability during development and adulthood. Due to the immaturity of sensory-motor capabilities of young pups, we chose as environmental stimulation a second lactating female, who provided extra maternal care and stimulation from birth. The results show that double mothering normalized the abnormal response to maternal separation in Oprm1 (-/-) pups and increased social motivation in juveniles and adult knockout mice. Additionally, we observed that Oprm1 (-/-) mice act as less attractive social partners than wild types, which suggests that social motivation can be modulated by the stimulus employed. This experiment supports previous findings suggesting that early social environmental stimulation has profound and long-term beneficial effects, encouraging the use of nonpharmacological interventions for the treatment of social defects in neurodevelopmental diseases. PMID- 27274877 TI - Aggressive Angiomyxoma in Pregnancy: A Rare Condition, a Common Misdiagnosis. AB - Introduction. Aggressive angiomyxoma is a rare mesenchymal neoplasm. Although benign in the majority of the cases, these neoplasms usually present a locally infiltrative nature and high rates of recurrence. Due to its rarity, misdiagnosis is a common problem. Case Presentation. We present one case of aggressive angiomyxoma in a 25-year-old pregnant woman. The patient presented with a large vaginal mass that was interpreted as a vaginal cyst. We performed surgical resection of the neoplasm and the correct diagnosis was only achieved after histological examination. With this case, we highlight the importance of considering this diagnosis in patients with genital and perineal masses of unknown origin and the impact of a correct preoperative diagnosis in patient's management and follow-up. Conclusion. Although aggressive angiomyxoma is rare, it should be considered in differential diagnosis of pelviperineal masses in young women. Its positivity to estrogen and progesterone receptors can justify enlargement and recurrence during pregnancy, although few cases are reported. Early recognition demands high index of suspicion for both gynaecologists and pathologists. Wide surgical excision with tumor free margins is the basis of curative treatment. Adjuvant therapy may be necessary for residual or recurrent tumors. Long-term follow-up is recommended. PMID- 27274878 TI - Bilateral, Simultaneous, Acute Angle Closure Glaucoma in Pseudophakia Induced by Chlorthalidone. AB - Purpose. To report two persons with acute, bilateral, and simultaneous angle closure glaucoma in pseudophakia secondary to uveal effusions induced by administration of chlorthalidone. Methods. CASE REPORTS: Results. Bilateral shallow anterior chambers and high intraocular pressure with decline in visual acuity were reported in two patients within days of intake of chlorthalidone for systemic hypertension. Gonioscopy confirmed appositional angle closure while choroidal detachment and ciliochoroidal detachment were revealed on ultrasonographic studies. Discontinuing chlorthalidone and institution of aqueous suppressants to reduce IOP and cycloplegics reversed angle closure and glaucoma. Conclusions. Reports of angle closure glaucoma in pseudophakic eyes induced by idiosyncratic reaction to chlorthalidone confirms that osmotic changes in the crystalline lens has no role in the pathogenesis of drug induced glaucoma and reaffirms that glaucoma is secondary to ciliochoroidal detachment and ciliary body rotation and edema. PMID- 27274879 TI - Extraction of a Large Central Airway Foreign Body Using Flexible Bronchoscopy Combined with an Endobronchial Blocker. AB - Adult foreign body (FB) aspiration is an uncommon but potentially fatal event. Options for extraction include flexible bronchoscopy (FLXB), rigid bronchoscopy (RB), and surgical extraction. We report the case of a large, smooth aspirated rock causing airway obstruction in an elderly male. RB is generally the preferred approach for extraction of a large complex FB; however, due to its size, the FB had to be removed using FLXB combined with an endobronchial blocker. In this report, we describe the anesthetic and surgical considerations and the novel technique used to extract the FB. PMID- 27274880 TI - A Giant Aggressive Angiomyxoma of the Pelvis Misdiagnosed as Incarcerated Femoral Hernia: A Case Report and Review of the Literature. AB - Aggressive angiomyxoma (AA) is an uncommon mesenchymal tumor that is mostly derived from the female pelvic and perineal regions. AA is a locally infiltrative slow growing tumor with a marked tendency to local recurrence. Painless swelling located around the genitofemoral region is the common symptom; thus, it is often misdiagnosed as a gynecological malignancy or a groin hernia. A 35-year-old female patient who previously underwent surgery for left femoral hernia operation resulting in surgical failure was reoperated for a giant AA located in the pelvis. The tumor was completely excised with free margins. Histopathologic examination revealed an AA. The tumor size was measured as 24 * 12 * 6 cm with a weight of 4.2 kg. Immunohistochemically, the cells show positive staining with vimentin, desmin, estrogen, and progesterone receptor. S100, MUC4, CD34, and SMA were negative in the tumor cells. AA should be considered in the differential diagnosis of any painless swelling located in the genitofemoral region, particularly in women of reproductive age. The principle treatment should be complete surgical excision with tumor-free margins. Long-term follow-up and careful monitoring are essential due to its high tendency of local recurrence in spite of wide excision of the tumor. Adjuvant antihormonal therapy yields promising results for preventing recurrence. PMID- 27274881 TI - Application of the Liver Maximum Function Capacity Test in Acute Liver Failure: A Helpful Tool for Decision-Making in Liver Transplantation? AB - Background. Despite aggressive intensive medical management acute liver failure (ALF) may require high-urgency liver transplantation (LTx). Available prognostic scores do not apply for all patients; reliable tools to identify individuals in need of LTx are highly required. The liver maximum function capacity test (LiMAx) might represent an appropriate option. Referring to a case of ALF after Amanita phalloides-intoxication the potential of the LiMAx-test in this setting is discussed. Presentation of Case. LiMAx was performed in a 27-year-old patient prior to and after high-urgency LTx. In accordance with clinical appearance of hepatic encephalopathy, coagulopathy, and acute kidney failure, the LiMAx-test constituted a fulminant course of ALF with hardly any detectable metabolic activity. Following LTx with a marginal donor organ (95% hepatosteatosis), uptake of liver function was demonstrated by postoperative increase of the LiMAx-value. The patient was discharged from hospital on postoperative day 26. Discussion. ALF often is associated with a critical state of the patient that requires almost immediate decision-making regarding further therapy. Application of a noninvasive liver function test might help to determine the prognosis of ALF and support decision-making for or against LTx as well as acceptance of a critical donor organ in case of a critically ill patient. PMID- 27274882 TI - An Expert Diagnosis System for Parkinson Disease Based on Genetic Algorithm Wavelet Kernel-Extreme Learning Machine. AB - Parkinson disease is a major public health problem all around the world. This paper proposes an expert disease diagnosis system for Parkinson disease based on genetic algorithm- (GA-) wavelet kernel- (WK-) Extreme Learning Machines (ELM). The classifier used in this paper is single layer neural network (SLNN) and it is trained by the ELM learning method. The Parkinson disease datasets are obtained from the UCI machine learning database. In wavelet kernel-Extreme Learning Machine (WK-ELM) structure, there are three adjustable parameters of wavelet kernel. These parameters and the numbers of hidden neurons play a major role in the performance of ELM. In this study, the optimum values of these parameters and the numbers of hidden neurons of ELM were obtained by using a genetic algorithm (GA). The performance of the proposed GA-WK-ELM method is evaluated using statical methods such as classification accuracy, sensitivity and specificity analysis, and ROC curves. The calculated highest classification accuracy of the proposed GA-WK-ELM method is found as 96.81%. PMID- 27274884 TI - Development and Characterization of Novel Floating-Mucoadhesive Tablets Bearing Venlafaxine Hydrochloride. AB - The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR) and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3) and citric acid were used as gas (CO2) generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72 +/- 2.49 seconds and duration of floating 24.50 +/- 0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF) at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr) and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr). PMID- 27274883 TI - Polycystic Ovary Syndrome May Be an Autoimmune Disorder. AB - Polycystic ovarian syndrome (PCOS) is the most prevalent endocrine disorder affecting females. It is a common cause of menstrual irregularities and infertility during reproductive age. Genetic and hormonal factors play crucial role in the pathogenesis of PCOS. Low level of progesterone in PCOS causes overstimulation of immune system that produces more estrogen which leads to various autoantibodies. Different autoantibodies have been documented in PCOS, for example, anti-nuclear (ANA), anti-thyroid, anti-spermatic, anti-SM, anti histone, anti-carbonic anhydrase, anti-ovarian, and anti-islet cell antibodies. There is an association between PCOS and autoimmune diseases such as ANA and anti TPO that have been documented in systemic lupus erythematosus and Hashimoto thyroiditis, respectively, and it is suspected that there are autoantibodies that might affect the long term clinical management of these patients. Therefore fluctuating levels of autoantibodies in different PCOS patients give us the way to open new chapter for future research on molecular level. This may lead to discovery of better treatment options for PCOS in near future. PMID- 27274885 TI - Environmental Risk Factors in Patients with Noninvasive Fungal Sinusitis. AB - Objective. The aim of our study was to try to determine the possible environmental risk factors for noninvasive fungal sinusitis in Egyptian patients. Methods. This is a prospective epidemiological case control study on the environmental risk factors of noninvasive fungal sinusitis. It included 60 patients and 100 age and sex matched controls. Results. There was a statistically significant relation between apartment floor, surface area, exposure to dust, exposure to cockroaches, poor air conditioning, and fungal sinusitis. Yet, no statistical significance was found between allergy related occupations, exposure to animals or plants, although their percentages were higher among cases, smoking, and urban or rural residence. Conclusion. We suggest that for patients with noninvasive fungal sinusitis a change in their living environment must be implied with better exposure to sunlight, larger well ventilated homes, proper cleaning of dust and cockroach extermination, and if possible the judicious use of air conditioners. PMID- 27274886 TI - Adaptability of Napiergrass (Pennisetum purpureum Schumach.) for Weed Control in Site of Animals Buried after Foot-and-Mouth Disease Infection. AB - After the infection of foot-and-mouth disease outbreaks in Miyazaki, Japan, in 2010, cattle and swine were slaughtered and buried in a site of 100 ha, where weed control is difficult and costly since lands are unlevelled and prohibited to be plowed for 3 years. To consider the adaptability of napiergrass (Pennisetum purpureum Schumach.) to the animal burial site for weed control, two napiergrass varieties, normal Wruk wona (WK) and dwarf late-heading variety (DL), were transplanted, compared with sowing of maize (MZ) and sorghum (SR) in both burial (BU) and neighboring bordered area (BO) in mid-June 2011. Even though several weed control methods were subjected to lands, MZ and SR failed to be established stably at only 1/3-1/2 due to the suppression of growth by indigenous weeds, while WK and DL successfully established as high as 82-91% and 73-85%, respectively, in 2011. The poor establishment of MZ and SR after sowing tended to be increased with the year from establishment. Plant dry matter yield and cellulose concentration were the highest in WK in 2011, while overwintering ability was constantly higher in DL in the 3 years. It is necessary to consider the utilization of forage plants on the animal burial site. PMID- 27274887 TI - Approach to bulbar urethral strictures: Which technique and when? AB - Bulbar urethra is the most common site of anterior urethral stricture and this stricture develops secondary to idiopathic (40%), iatrogenic (35%), inflammatory (10%), and traumatic (15%) causes. Various techniques and approaches with buccal mucosal graft have been described. We wanted to describe different techniques of repair with specific advantages. PMID- 27274888 TI - TMPRSS2-ERG gene fusion in Turkish patients with localized prostate cancer: results of radical prostatectomy specimens. AB - OBJECTIVE: Our aim was to evaluate and determine the frequency of Transmembrane protease, serine 2 (TMPRSS2)-ERG fusion in Turkish patients with clinically localized prostate cancer by using immunohistochemistry and reveal its relationship with clinicopathologic variables. MATERIAL AND METHODS: Radical prostatectomy specimens of 99 patients, who underwent radical retropubic prostatectomy for localized cancer, between January 2002 and December 2011 were analyzed in the study. To detect ERG fusions, monoclonal ERG antibodyclone ID: EPR3864 (Epitomics, San Diego, CA, USA) and monoclonal anti-ERG antibody (9FY) (BiocareMedical, LLC, USA) were used. The immunistochemical expression of ERG protein was assessed as positive or negative regardless of stain intensity. Patients' age, total and primary Gleason scores, PSA levels, prostate volumes, tumor volumes, tumor stages and perineural invasion status were analysed retrospectively. Total fusion rate and correlation between the variables and fusion were evaluated. RESULTS: Mean age, prostate volume, tumor volume, PSA value of 99 patients were 62.02 years (+/-5.93), 50.02 cc (+/-20.67), 3.19 cc (+/ 4.16), and 9.34 ng/mL (+/-3.37) respectively. TMPRSS2-ERG fusion was seen in 46 (46.5%) of 99 patients. When the variables analysed with independent samples t test to predict fusion (+) status, none of them was found to be statistically significant. When evaluated by logistic regression analysis for (+) or (-) status, only tumor stage was found to be statistically significantly correlated with fusion (p=0.049). CONCLUSION: The incidence of TMPRSS-ERG fusion in patients with localised prostate cancer in our study with Turkish population was found as 46.5%. Only tumor stage correlated with TMPRSS2-ERG fusion. PMID- 27274889 TI - The effect of ureteroscope size in the treatment of ureteral stone: 15-year experience of an endoscopist. AB - OBJECTIVE: We aimed to investigate the ureter stone treatment results performed by using different- caliber semirigid ureteroscopes (URS). MATERIAL AND METHODS: Adult patients who were treated for ureteral stones by a single endoscopist between January 2000 and March 2015 were analyzed. The patients were divided into 3 groups in accordance with the caliber of the ureteroscope used: 10/10.5 F Storz (Karl Storz, Tuttlingen, Germany) (January 2002-January 2005) URS was used in group 1, 8.9/9.8 F Storz (February 2005-December 2011) URS was used in group 2, and 6/7.5 FWolf (Richard Wolf, Knittlingen, Germany) (January 2012-March 2015) URS was used in group 3. Patients' age and gender, size and site of stones, stone free rates (SFR), intra- and perioperative complication rates, and durations of surgery were compared among the groups. Intraoperative complications were classified according to modified Satava, and perioperative complications were classified according to modified Clavien classification systems. RESULTS: A total of 2461 patients treated for ureteral stones were analyzed. There were 583 patients in group 1 (10/10.5 F Storz), 1302 patients in group 2 (8.9/9.8 F Storz), and 576 patients in group 3 (6/7.5 F Wolf). SFR were 83.7%, 87.4%, and 92.2% in groups 1, 2, and 3, respectively (p=0.01). Duration of surgery was 30.34+/-10.36 min in group 1, 31.61+/-10.10 min in group 2, and 42.40+/-7.35 min in group 3 (p=0.01). The overall complication rates classified according to modified Satava classification were 10.8%, 7.6%, and 6.9% (p=0.01) while grade 3 modified Satava complication rates were 1.9%, 1.5%and 0.5% in groups 1, 2, and 3, respectively (p=0.01). CONCLUSION: In this study, we found that more frequent use of a small- caliber URS resulted in a longer duration of surgery and an increased rate for JJ stent insertion, however it facilitated a safer and more successful ureteroscopy procedure. PMID- 27274890 TI - Evaluation of the complications in transperitoneal laparoscopic renal and adrenal surgery with Clavien-Dindo classification. AB - OBJECTIVE: To evaluate our complications in renal and adrenal transperitoneal laparoscopic surgeries with Clavien-Dindo classification. MATERIAL AND METHODS: Two hundred and eight patients to whom renal and adrenal laparoscopic surgeries were performed between January 2008 and June 2015 were included the study. One hundred and twenty one (58.2%) patients were female and 87 (41.8%) of them were male. Laparoscopic procedures were performed as radical nephrectomy (n=49; 23.6%), simple nephrectomy (n=56; 26.9%), and partial nephrectomy (n=7; 3.4%), renal cyst decortication (n=27; 13%), pyelopasty (n=14; 6.7%) and adrenalectomy (n=55; 26.4%). Complications were classified according to Clavien-Dindo classification. RESULTS: The mean age of the patients was 48.01+/-14.9 years. The mean duration of hospital stay was 3.5+/-1.9 days. According to European Scoring System for Laparoscopic Operations the procedures were graded based on procedural difficulty as simple (n=27; 12.9%), difficult (n=172; 82.8%), and highly difficult (n=9; 4.3%). Complications were observed in 13 (6.3%) interventions. One of these occurred during very hard and 14 during difficult procedures. According to Clavien-Dindo Classification; Grades 1, 2, and 3 A complications developed in 3 (1.4%), 9 (4.3%), and 1(0.5%) patient, respectively. CONCLUSION: Laparoscopic surgery is an efficient procedure in well-chosen patients for renal and adrenal diseases with low complication rates. PMID- 27274891 TI - Clinical and histopathological results of the adult patients with unilateral cryptorchidism. AB - OBJECTIVE: To evaluate the clinical and histopathological results of adult unilateral cryptorchidism patients. MATERIAL AND METHODS: Data from adult unilateral cryptorchidism patients that underwent orchiectomy in our clinic between between January 2004 and March 2013 were retrospectively evaluated. Patients were divided into three groups as intra-abdominal, inguinal canal and superficial inguinal region according to the location of the undescended testes. Patients were also grouped according to their testicular volume (<4 cc, 4.1-12 cc, and >12 cc). Histopathology results of orchiectomy specimens were classified as follows: 1. Sertoli cells only, testicular atrophy and vanished testis (anorchia) 2. Hypospermatogenesis, and 3. Maturation arrest. Patients were grouped as normospermia, azoospermia and oligo/astheno/teratospermia groups according to semen analysis results. Correlations between testicular localization, testicular size, semen analysis and pathology results were evaluated. Incidental tumor detection rates were also calculated. RESULTS: Two hundred and forty-four adult unilateral cryptorchidism patients underwent orchiectomy in our clinic. There was no a significant relationship between location of the testis and testicular pathology results (p=0.707). Most common semen analysis results was normospermia in patients with high testicular volume group however azoospermia and oligoasthenospermia observed commonly in patients with low testicular volume group. There was a significant relationship between testicular volume and semen analysis results (p=0.023). No significant relationship was observed between semen analysis and pathological results (p=0.929). After an evaluation of all factors with possible effects on the semen analysis results, only testicular volume (p=0.036) was found to have a significant impact. Only one case (0.4%) was incidentally diagnosed seminoma after a review of 233 patients with available histopathological results on record. CONCLUSION: Adult unilateral cryptorchidism has a minimal effect on male fertility or even this effect can be overlooked. Low detection rates of incidental germ cell tumors also make an orchiectomy decision questionable in such cases. PMID- 27274892 TI - Early removal of urinary catheter after excision and primary anastomosis in anterior urethral stricture. AB - OBJECTIVE: To investigate the feasibility of removing the urinary catheter 7 days after excision and primary anastomosis (EPA) performed with the indication of anterior urethral stricture disease. MATERIAL AND METHODS: Retrospective review of medical records of the patients who had undergone EPA between January 2005 and December 2010 was performed. These patients were divided into 2 groups: Group 1 (urethral catheter removed on or before 7. postoperative day) and Group 2 (urethral catheter removed on 8. postoperative day or later). We compared 2 groups as for the frequency of extravasation as detected on retrograde pericatheter urethrogram (PUG) and recurrence rate till the last follow-up. RESULTS: PUG was performed on an average day 7 and 14 in Groups 1 (n=102) and 2 (n=134), respectively followed by removal of the catheter. Extravasation on the first PUG was detected in 6.8% of the patients in Group 1, and in 4.5% of the cases in Group 2 had extravasation on the first PUG. Urethral catheter was left in situ in these patients and a repeat PUG after one week was performed which was normal in all cases. The incidence of extravasation and recurrence rate did not differ significantly whether catheter was removed on day 7 or 14 (6.8% vs. 4.5% and 4.9% vs. 5.2% respectively) (p>0.5). CONCLUSION: We conclude that removal of the catheter on postoperative day 7 after EPA does not increase the rate of extravasation and recurrence during long-term follow-up. Urethral catheter restricts physical activity in the postoperative period which is bothersome to the patient. Hence early removal of a catheter should be offered to men after EPA. PMID- 27274893 TI - Comparison of sonoelastography with sonourethrography and retrograde urethrography in the evaluation of male anterior urethral strictures. AB - OBJECTIVE: Retrograde urethrography (RUG) is the most common and preferred imaging modality for imaging of the anterior urethral strictures despite its well known limitations and disadvantages. Sonourethrography (SUG) was introduced in 1988 to overcome the limitations of RUG and to provide more accurate results. As proper selection of imaging modality is very important for planning the treatment, various advances in this area are required. One of the major factors for recurrence of stricture disease is spongiofibrosis. Sonoelastography (SE) is a newer technique, tried in various other pathologies. In this study, we have used this technique for the first time to assess its efficacy in the evaluation of anterior urethral stricture disease by comparison with RUG and SUG. MATERIAL AND METHODS: Between August 2014 and May 2015, 77 patients with clinical features of anterior urethral stricture disease were included in the study and evaluated by RUG followed by SUG and SE for stricture location, length, depth of spongiofibrosis and periurethral pathologies. The results were then correlated with operative and histopathological findings. RESULTS: Overall diagnostic accuracy of SE, SUG, and RGU for the estimation of stricture location, and length were estimated 92.68% vs. 91.54%, 79% vs. 78.87% and 80.48% vs. 43.66%, respectively, while for depth of spongiofibrosis SE, and SUG had accuracy rates of 87.3%, 48%, respectively. The mean length measured on SE was nearest to the mean intra-operative stricture length (21.34+11.8 mm). SE findings significantly correlated with the colour of bladder mucosa on cystoscopic examination (p=0.003) whereas the association was non-significant (p=0.127) for difficulty in incision. While a nonsignificant correlation existed between SUG findings related both to the colour of the bladder mucosa and difficulty in incision on cystoscopy, SE findings had a significant association (p<0.001) with histopathology findings for severe degree of fibrosis. CONCLUSION: Sonoelastography estimates stricture site and length better in comparison with RUG and SUG. It estimates degree of spongiofibrosis which serves as an important prognostic factor for stricture recurrence more accurately than SUG. PMID- 27274894 TI - 2% Lidocaine gel or plain lubricating gel: Which one should be used in male flexible cystoscopy? AB - OBJECTIVE: To investigate and compare the effects on pain of intraurethral 2% lidocaine gel and plain lubricating gel in male patients underwent flexible cystoscopy. MATERIAL AND METHODS: The data of 220 male patients who underwent flexible cystoscopy between March 2012 and August 2014 were retrospectively analized. The patients were divided into 2 groups according to using intraurethral gel types. Group I included 120 patients who were underwent flexible cystoscopy with 2% lidocaine gel and Group II was consisted from 100 patients who underwent flexible cystoscopy with plain lubricating gel. The groups were compared according to postprocedure data including pain score, procedure time and age of patients. RESULTS: The mean age of the patients in Group I was 50.02+/-11.87 years while that in Group II was 52.03+/-13.37 years (p=0.492). The mean procedure times were 6.02+/-0.787 and 6.28+/-0.689 minutes in Group I and Group II respectively (p=0.061). Pain perception scores were not statistically different between the groups (Group I: 3.10+/-0.980, Group II: 3.34+/-0.789, p=0.132). CONCLUSION: Use of intraurethral 2% lidocaine gel has no advantage over plain lubricating gel in regard to pain control during flexible cystoscopy in men. PMID- 27274895 TI - Assessment of bladder wall thickness in women with overactive bladder. AB - OBJECTIVE: To compare bladder wall thickness (BWT) between female patients with overactive bladder (OAB) and aged-matched healthy controls. MATERIAL AND METHODS: Thirty-six female patients with OAB and 31 healthy women were enrolled in the present prospective observational study. Qmax and Qave were measured by using uroflowmetry in all of the women in the patient and control groups, and also maximum bladder capacity (MBC), post- void residual urine (PVRU), prevoiding and postvoiding BWT were measured by using transabdominal ultrasound. Lower urinary tract symptoms of the participants were assessed by using Overactive Bladder Version-8 (OAB-V8) and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF). All of the data were statistically compared between the patient and control groups. In the patient group, the relationships between parameters were evaluated correlation analysis. RESULTS: The mean age of the patients and controls were similar (respectively, 45.58+/-12.35 and 44.21+/-11.60 years (p=0.68). The mean pre- and post-voiding BWT, OAB-V8 and ICIQ-SF scores of the patients were significantly higher than the controls. In the patient group, the moderate positive correlations between BWT with Qmax (p=0.02) and Qave (p=0.02) were found. CONCLUSION: This study showed that the BWTs of the female patients with OAB are higher than those of healthy women. Further studies should investigate the changes in BWT of patients with OAB after treatment of OAB. PMID- 27274896 TI - Hamartoma of the urinary bladder in a 15-year-old boy. AB - Hamartoma of the bladder is an unusual entity described in only eleven patients to date. It may present as painless hematuria, irritative urinary tract symptoms, or inability to void or it may be diagnosed incidentally. Hamartoma of the bladder may be isolated or occur as part of a syndrome. No isolated bladder hamartoma to date has shown malignant potential. We describe here a bladder hamartoma in a 15-year-old boy. PMID- 27274897 TI - Gastric metastasis of renal cell carcinoma 20 years after radical nephrectomy. AB - Renal cell carcinomas account for 2-3% of malignant neoplasms in adults. The lung, soft tissues and bone represent the most frequent sites of distant metastasis in renal cell carcinoma. Gastric metastasis is rare. Our case was a 72 year-old man with complaints of fatigue and loss of appetite. In history, he had unergone radical nephrectomy due to renal cell carcinoma in 1993. A polypoid lesion was observed in upper gastrointestinal endoscopy. Histopathology of gastric biopsy specimen was reported as renal cell carcinoma. In English literature, there are 50 cases diagnosed as gastric metastasis from renal cell carcinoma. To date, there are only 4 cases with extremely late gastric metastasis of renal cell carcinoma. Herein, we present a rare case which underwent radical nephrectomy due to renal cell carcinoma and found to have gastric metastasis at 20. year of his follow-up. PMID- 27274898 TI - A rare cause of ureteral injuries; simultaneous common iliac artery and ureter injury during posterior lumbar disc surgery. AB - Major vascular injuries during lumbar disc surgery are rare but well-recognized complications. However, vascular injuries of the branches of the aorta and ureteral injuries are very rare. Although its incidence is not known definitely, it is estimated to be 1/1000. Ureteral injuries comprise less than 1% of all genitourinary traumas. In this article, we report clinical progress of a patient who had simultaneous internal iliac artery and ureteral injury during lumbar discectomy. The patient was managed with primary ureteroureterostomy. To our knowledge, this is the first case reported with simultaneous ureter and iliac artery trauma during lumbar disc surgery. PMID- 27274899 TI - Surgical reconstruction in female genital mutilation. AB - Female genital mutilation (FGM) is an unusual condition for our country. However, an increase in FGM in future days can be predicted with the increasing numbers of exchange students coming from African countries, migration of refugees and socioeconomic relations with the African countries. We want to share our experience of two FGM victims admitted to our clinic with the request of reconstructive vulvar surgery before their marriage. Both women had WHO Type III FGM. Physical examination findings and surgical reconstruction techniques were presented. PMID- 27274900 TI - RE: Percutaneous nephrolithotomy for isolated calyceal stones: How important is the stone location? PMID- 27274901 TI - Training problems of residents in urology. PMID- 27274902 TI - Late-Stage Diversification of Biologically Active Molecules via Chemoenzymatic C H Functionalization. AB - Engineered variants of rebeccamycin halogenase were used to selectively halogenate a number of biologically active aromatic compounds. Subsequent Pd catalyzed cross-coupling reactions on the crude extracts of these reactions were used to install aryl, amine, and ether substituents at the halogenation site. This simple, chemoenzymatic method enables non-directed functionalization of C-H bonds on a range of substrates to provide access to derivatives that would be challenging or inefficient to prepare by other means. PMID- 27274903 TI - Drug Use and Spatial Dynamics of Household Allocation. AB - : Household space allocation by women who consume drugs in New York and North Florida is depicted to demonstrate the complex character of household space and social relations. Some parents attempt to hide their drug consumption through the allocation space in the household for drug use. Women allocation of space for drug use within their households and the impact of this on the household are relevant issues with implications for therapy and prevention. OBJECTIVE: The use of household space has not been a focus of social scientists. Middle class households have been used by decoration literature to specify space utilization. Modest literature pay attention to the utilization of household space among drug focused households. Analysis herein looks at the lived social relations of drug users to their children through controlling household space. METHODS: Data presented comes from two studies, New York and Florida. The studies involved a total of 158 participants in 72 families from New York and 26 participants in 23 families in North Florida. Both researches used an ethnographic methodology focusing on a variety of behavior patterns and conduct norms occurring within drug abusing households. Repeated interviews and observations took place in households which were visited at different times and days of the week. Florida study was conducted over a 2-year period; New York study took place over a 5-year period. RESULTS: Data suggest parents attempted to conceal their drug use from their offspring by using various strategies. Mental, social, and physical were tied together in space allocation. Household space acquired a different meaning and arose from use practice. CONCLUSION: In urban and rural settings a pattern of household allocation space and drug consumption is emerging. Although drug consumption is still prominent, it is not all consuming or the primary focus in the lives of women who use drugs. These women may have learned to integrate their consumption into their daily household/family life through the reallocation of space in their homes. PMID- 27274904 TI - Implementation of Computer-delivered Brief Alcohol Intervention in HIV Clinical Settings: Who Agrees to Participate? AB - OBJECTIVE: Addressing alcohol use in primary HIV settings can improve medical outcomes and overall quality of life of persons living with HIV (PLWH). In order to assess the feasibility of computer-delivered brief alcohol intervention (CBI) and to inform future efforts to improve access to CBI, we examined patient-level socio-demographic, clinical and behavioral characteristics associated with agreement to participate in CBI among non-treatment seeking PLWH with alcohol misuse. METHODS: Participants were recruited from two Centres for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) HIV clinics. PLWH completed a clinical assessment of patient-reported measures and outcomes using tablet based assessments, including socio-demographic and behavioural characteristics. HIV biological indicators, i.e., CD4 count and viral load, were also available from the electronic medical record. Participants were approached for CBI participation based on scores on the Alcohol Use Disorders Identification Test (AUDIT); no incentives were offered for CBI participation. We performed chi square tests, analysis of variance and multivariate logistic regression to compare socio-demographic, behavioural and clinical factors among participants who agreed to participate compared with those who refused/postponed participation. RESULTS: We observed that 42% of non-treatment seeking, non incentivized PLWH with alcohol misuse provided written agreement to participate in on-site CBI delivered in their HIV primary care clinic. A larger proportion of PLWH who agreed to enrol in CBI had detectable viral loads, heavier weekly alcohol use, and higher DSM-5 alcohol use disorder symptom counts and mental health symptoms. Neither socio-demographic background nor drug use status was associated with CBI enrolment. CONCLUSION: CBI implementation reached those patients most in need of care. The findings of this study may assist HIV-care providers to better identify appropriate patients and initiate discussions to facilitate the participation of PLWH in alcohol intervention services. PMID- 27274905 TI - Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity. AB - Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes. PMID- 27274906 TI - Adoptive Transfer of Dendritic Cells Expressing Fas Ligand Modulates Intestinal Inflammation in a Model of Inflammatory Bowel Disease. AB - BACKGROUND: Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory conditions of unknown cause and likely result from the loss of immunological tolerance, which leads to over-activation of the gut immune system. Gut macrophages and dendritic cells (DCs) are essential for maintaining tolerance, but can also contribute to the inflammatory response in conditions such as IBD. Current therapies for IBD are limited by high costs and unwanted toxicities and side effects. The possibility of reducing intestinal inflammation with DCs genetically engineered to over-express the apoptosis-inducing FasL (FasL-DCs) has not yet been explored. OBJECTIVE: Investigate the immunomodulatory effect of administering FasL-DCs in the rat trinitrobenzene sulfonic acid (TNBS) model of acute colitis. METHODS: Expression of FasL on DCs isolated from the mesenteric lymph nodes (MLNs) of normal and TNBS-colitis rats was determined by flow cytometry. Primary rat bone marrow DCs were transfected with rat FasL plasmid (FasL-DCs) or empty vector (EV-DCs). The effect of these DCs on T cell IFNgamma secretion and apoptosis was determined by ELISPOT and flow cytometry for Annexin V, respectively. Rats received FasL-DCs or EV-DCs intraperitoneally 96 and 48 hours prior to colitis induction with TNBS. Colonic T cell and neutrophil infiltration was determined by immunohistochemistry for CD3 and myeloperoxidase activity assay, respectively. Macrophage number and phenotype was measured by double immunofluorescence for CD68 and inducible Nitric Oxide Synthase. RESULTS: MLN dendritic cells from normal rats expressed more FasL than those from colitic rats. Compared to EV-DCs, FasL-DCs reduced T cell IFNgamma secretion and increased T cell apoptosis in vitro. Adoptive transfer of FasL-DCs decreased macroscopic and microscopic damage scores and reduced colonic T cells, neutrophils, and proinflammatory macrophages when compared to EV-DC adoptive transfer. CONCLUSION: FasL-DCs are effective at treating colonic inflammation in this model of IBD and represent a possible new treatment for patients with IBD. PMID- 27274907 TI - Restoration of Retarded Influenza Virus-specific Immunoglobulin Class Switch in Aged Mice. AB - OBJECTIVE: The declined immune response to infection causes significant higher morbidity and mortality in aging in spite of the coexisted hyperimmunoglobulinemia (HIG). This study is to reveal the cellular basis of HIG and mechanism of weakened HA-specific IgG response in aged mice and to test cell therapy in the treatment of age-related IgG antibody production deficiency with immunocyte adoptive transfer. METHODS: BALB/c mice was immunized with Influenza A/Taiwan vaccine and challenged with the same strain of virus. ELISA was used to assess the levels of total immunoglobulins and antigen specific antibody response. The flow cytometry and ELISPOT were used to evaluate the frequencies of total immunoglobulin- and specific antibody-producing and secreting B lymphocytes. In vitro expanded mononuclear cells, CD4+ T lymphocytes and CD20+ B lymphocytes from old and young mice were adoptively transferred into influenza virus-challenged aged mice, and HA-specific IgG responses were observed. RESULTS: It is found that old mice exhibited higher levels of total serum IgG, IgM and IgA, higher frequencies of IgG+, IgM+ and IgA+ cells, and greater antigen specific IgM and IgA responses to influenza infection, in comparison to young mice. However, influenza antigen- specific IgG and its subclass responses in old mice were significantly lower. CONCLUSION: The retarded specific IgG response could be attributed to an insufficiency of immunoglobulin class switch in aging. Correlation analysis indicated that HIG and deficient specific IgG production in aged mice could be independent to each other in their pathogenesis. Correction of deficient specific IgG production by adoptive transfer of in vitro expanded and unexpanded CD4+ cells from immunized young mice suggests the CD4+ cell dysfunction contributes to the insufficiency of immunoglobulin class switch in aged mice. The transfusion of in vitro expanded lymphocytes could be a potential effective therapy for the age-related immunodeficiency and could play a role in the infection prevention in aging. PMID- 27274909 TI - Soluble material secreted from Penicillium chrysogenum isolate exhibits antifungal activity against Cryphonectria parasitica- the causative agent of the American Chestnut Blight. AB - The American chestnut (Castanea dentata) was once the dominant canopy tree along the eastern region of the United States. Cryphonectria parasitica, the causative agent of chestnut blight, was introduced from Asia in the early 1900's, and obliterated the chestnut population within 50 years. We sought to identify environmental microbes capable of producing factors that were fungicidal or inhibited growth of C. parasitica in the hopes developing a biological control of chestnut blight. We isolated a filamentous fungus that significantly inhibited the growth of C. parasitica upon co-cultivation. Extracellular fractions of this fungal isolate prevented C. parasitica growth, indicating that a potential fungicide was produced by the novel isolate. Sequence analysis of 18S rRNA identified this inhibitory fungus as Penicillium chrysogenum. Furthermore, these extracellular fractions were tested as treatments for blight in vivo using chestnut saplings. Scarred saplings that were treated with the P. chrysogenum extracellular fractions healed subjectively better than those without treatment when inoculated with C. parasitica. These data suggest that material secreted by P. chrysogenum could be used as a treatment for the American chestnut blight. This work may assist the reclamation of the American chestnut in association with breeding programs and blight attenuation. Specifically, treatment of small groves under the right conditions may allow them to remain blight free. Future work will explore the mechanism of action and specific target of the extracellular fraction. PMID- 27274908 TI - Magnetofection Enhances Adenoviral Vector-based Gene Delivery in Skeletal Muscle Cells. AB - The goal of magnetic field-assisted gene transfer is to enhance internalization of exogenous nucleic acids by association with magnetic nanoparticles (MNPs). This technique named magnetofection is particularly useful in difficult-to transfect cells. It is well known that human, mouse, and rat skeletal muscle cells suffer a maturation-dependent loss of susceptibility to Recombinant Adenoviral vector (RAd) uptake. In postnatal, fully differentiated myofibers, the expression of the primary Coxsackie and Adenoviral membrane receptor (CAR) is severely downregulated representing a main hurdle for the use of these vectors in gene transfer/therapy. Here we demonstrate that assembling of Recombinant Adenoviral vectors with suitable iron oxide MNPs into magneto-adenovectors (RAd MNP) and further exposure to a gradient magnetic field enables to efficiently overcome transduction resistance in skeletal muscle cells. Expression of Green Fluorescent Protein and Insulin-like Growth Factor 1 was significantly enhanced after magnetofection with RAd-MNPs complexes in C2C12 myotubes in vitro and mouse skeletal muscle in vivo when compared to transduction with naked virus. These results provide evidence that magnetofection, mainly due to its membrane-receptor independent mechanism, constitutes a simple and effective alternative to current methods for gene transfer into traditionally hard-to-transfect biological models. PMID- 27274910 TI - Ataxia with Vitamin E Deficiency May Present with Cervical Dystonia. AB - BACKGROUND: Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disorder that usually presents with ataxia, areflexia, and proprioceptive and vibratory sensory loss. Dystonia has been reported rarely. CASE REPORT: An 11 year-old female presented with dystonic head tremor and cervical and bilateral arm dystonia. Her 14-year-old older brother had dystonic head tremor and generalized dystonia. One year later, the brother developed dysarthria, limb dysmetria, and gait ataxia. Compound heterozygous mutations in TTPA were detected, confirming the diagnosis of AVED. DISCUSSION: AVED may present with dystonia rather than ataxia, and should be considered in the differential diagnosis of progressive dystonia. PMID- 27274911 TI - Multicollinearity in Regression Analyses Conducted in Epidemiologic Studies. AB - The adverse impact of ignoring multicollinearity on findings and data interpretation in regression analysis is very well documented in the statistical literature. The failure to identify and report multicollinearity could result in misleading interpretations of the results. A review of epidemiological literature in PubMed from January 2004 to December 2013, illustrated the need for a greater attention to identifying and minimizing the effect of multicollinearity in analysis of data from epidemiologic studies. We used simulated datasets and real life data from the Cameron County Hispanic Cohort to demonstrate the adverse effects of multicollinearity in the regression analysis and encourage researchers to consider the diagnostic for multicollinearity as one of the steps in regression analysis. PMID- 27274913 TI - Optical Diffraction in Close Proximity to Plane Apertures. IV. Test of a Pseudo Vectorial Theory. AB - Rayleigh's pseudo-vectorial theory of the diffraction of polarized light by apertures which are small compared to the wavelength of light is analyzed with respect to its mathematical rigor and physical significance. It is found that the results published by Rayleigh and Bouwkamp for s-polarized incident do not obey the conditions assumed in their derivation and must therefore be dismissed. It is also found that the theory leads to paradoxical predictions concerning the polarization of the diffracted field, so that the pseudo-vectorial approach is intrinsically incapable of describing polarization effects. PMID- 27274914 TI - A Summary of Lightpipe Radiation Thermometry Research at NIST. AB - During the last 10 years, research in light-pipe radiation thermometry has significantly reduced the uncertainties for temperature measurements in semiconductor processing. The National Institute of Standards and Technology (NIST) has improved the calibration of lightpipe radiation thermometers (LPRTs), the characterization procedures for LPRTs, the in situ calibration of LPRTs using thin-film thermocouple (TFTC) test wafers, and the application of model-based corrections to improve LPRT spectral radiance temperatures. Collaboration with industry on implementing techniques and ideas established at NIST has led to improvements in temperature measurements in semiconductor processing. LPRTs have been successfully calibrated at NIST for rapid thermal processing (RTP) applications using a sodium heat-pipe blackbody between 700 degrees C and 900 degrees C with an uncertainty of about 0.3 degrees C (k = 1) traceable to the International Temperature Scale of 1990. Employing appropriate effective emissivity models, LPRTs have been used to determine the wafer temperature in the NIST RTP Test Bed with an uncertainty of 3.5 degrees C. Using a TFTC wafer for calibration, the LPRT can measure the wafer temperature in the NIST RTP Test Bed with an uncertainty of 2.3 degrees C. Collaborations with industry in characterizing and calibrating LPRTs will be summarized, and future directions for LPRT research will be discussed. PMID- 27274915 TI - A Tale About the First Weights and Measures Intercomparison in the United States in 1832. AB - In preparation for the Hassler memorial tablet dedication in the National Institute of Standards and Technology (NIST) Administration Building lobby in December of 2004, I learned that Ferdinand Rudolph Hassler had carried out the first systematic study of weights and measures in the United States. I obtained a copy of Comparison of Weights and Measures of Length and Capacity Reported to the Senate of the United States which is Hassler's 1832 report to Congress on this comparison that related all the weights and measures then in use by the states and federal customhouses. Handwritten inscriptions in the book reveal interesting facts about Hassler's work and his communication with other scientists in Europe at that time. PMID- 27274916 TI - Phase Transformations in the High-Tc Superconducting Compounds, Ba2RCu3O7-delta (R = Nd, Sm, Gd, Y, Ho, and Er). AB - The phase transformation between the orthorhombic and tetragonal structures of six high-T c superconductors, Ba2RCu3O7- delta , where R = Nd, Sm, Gd, Y, Ho, and Er, and delta = 0 to 1, has been investigated using techniques of x-ray diffraction, differential thermal analysis/thermogravimetric analysis (DTA/TGA) and electron diffraction. The transformation from the oxygen-rich orthorhombic phase to the oxygen-deficient tetragonal phase involves two orthorhombic phases. A superlattice cell caused by oxygen ordering, with a' = 2a, was observed for materials with smaller ionic radius (Y, Ho, and Er). For the larger lanthanide samples (Nd, Sm, and Gd), the a' = 2a type superlattice cell was not observed. The structural phase transition temperatures, oxygen stoichiometry and characteristics of the T c plateaus appear to correlate with the ionic radius, which varies based on the number of f electrons. Lanthanide elements with a smaller ionic radius stabilize the orthorhombic phase to higher temperatures and lower oxygen content. Also, the superconducting temperature is less sensitive to the oxygen content for materials with smaller ionic radius. The trend of dependence of the phase transformation temperature on ionic radius across the lanthanide series can be explained using a quasi-chemical approximation (QCA) whereby the strain effect plays an important role on the order-disorder transition due to the effect of oxygen content on the CuO chain sites. PMID- 27274917 TI - An Examination of New Paradigms for Spline Approximations. AB - Lavery splines are examined in the univariate and bivariate cases. In both instances relaxation based algorithms for approximate calculation of Lavery splines are proposed. Following previous work Gilsinn, et al. [7] addressing the bivariate case, a rotationally invariant functional is assumed. The version of bivariate splines proposed in this paper also aims at irregularly spaced data and uses Hseih-Clough-Tocher elements based on the triangulated irregular network (TIN) concept. In this paper, the univariate case, however, is investigated in greater detail so as to further the understanding of the bivariate case. PMID- 27274918 TI - Integer Representation of Decimal Numbers for Exact Computations. AB - A scheme is presented and software is documented for representing as integers input decimal numbers that have been stored in a computer as double precision floating point numbers and for carrying out multiplications, additions and subtractions based on these numbers in an exact manner. The input decimal numbers must not have more than nine digits to the left of the decimal point. The decimal fractions of their floating point representations are all first rounded off at a prespecified location, a location no more than nine digits away from the decimal point. The number of digits to the left of the decimal point for each input number besides not being allowed to exceed nine must then be such that the total number of digits from the leftmost digit of the number to the location where round-off is to occur does not exceed fourteen. PMID- 27274912 TI - Microbiota and Neurological Disorders: A Gut Feeling. AB - In the past century, noncommunicable diseases have surpassed infectious diseases as the principal cause of sickness and death, worldwide. Trillions of commensal microbes live in and on our body, and constitute the human microbiome. The vast majority of these microorganisms are maternally derived and live in the gut, where they perform functions essential to our health and survival, including: digesting food, activating certain drugs, producing short-chain fatty acids (which help to modulate gene expression by inhibiting the deacetylation of histone proteins), generating anti-inflammatory substances, and playing a fundamental role in the induction, training, and function of our immune system. Among the many roles the microbiome ultimately plays, it mitigates against untoward effects from our exposure to the environment by forming a biotic shield between us and the outside world. The importance of physical activity coupled with a balanced and healthy diet in the maintenance of our well-being has been recognized since antiquity. However, it is only recently that characterization of the host-microbiome intermetabolic and crosstalk pathways has come to the forefront in studying therapeutic design. As reviewed in this report, synthetic biology shows potential in developing microorganisms for correcting pathogenic dysbiosis (gut microbiota-host maladaptation), although this has yet to be proven. However, the development and use of small molecule drugs have a long and successful history in the clinic, with small molecule histone deacetylase inhibitors representing one relevant example already approved to treat cancer and other disorders. Moreover, preclinical research suggests that epigenetic treatment of neurological conditions holds significant promise. With the mouth being an extension of the digestive tract, it presents a readily accessible diagnostic site for the early detection of potential unhealthy pathogens resident in the gut. Taken together, the data outlined herein provide an encouraging roadmap toward important new medicines and companion diagnostic platforms in a wide range of therapeutic indications. PMID- 27274919 TI - One-Center Location With Block and Euclidean Distance. AB - A geometrical analysis is made of the dual simplex algorithm applied to a linear programming formulation of the one-center location problem in IR (2) using block distance. A geometric rule is given, and shown to be equivalent to the minimum ratio rule of the simplex algorithm, for updating the dual basis. The geometric analysis is applied to the Euclidean distance one-center problem and yields an alternative updating procedure for the dual algorithm. PMID- 27274920 TI - Optimal Facility-Location. AB - Dr. Christoph Witzgall, the honoree of this Symposium, can count among his many contributions to applied mathematics and mathematical operations research a body of widely-recognized work on the optimal location of facilities. The present paper offers to non-specialists a sketch of that field and its evolution, with emphasis on areas most closely related to Witzgall's research at NBS/NIST. PMID- 27274921 TI - Optimization Models for Scheduling of Jobs. AB - This work is motivated by a particular scheduling problem that is faced by logistics centers that perform aircraft maintenance and modification. Here we concentrate on a single facility (hangar) which is equipped with several work stations (bays). Specifically, a number of jobs have already been scheduled for processing at the facility; the starting times, durations, and work station assignments for these jobs are assumed to be known. We are interested in how best to schedule a number of new jobs that the facility will be processing in the near future. We first develop a mixed integer quadratic programming model (MIQP) for this problem. Since the exact solution of this MIQP formulation is time consuming, we develop a heuristic procedure, based on existing bin packing techniques. This heuristic is further enhanced by application of certain local optimality conditions. PMID- 27274922 TI - Fast Algorithms for Structured Least Squares and Total Least Squares Problems. AB - We consider the problem of solving least squares problems involving a matrix M of small displacement rank with respect to two matrices Z 1 and Z 2. We develop formulas for the generators of the matrix M (H) M in terms of the generators of M and show that the Cholesky factorization of the matrix M (H) M can be computed quickly if Z 1 is close to unitary and Z 2 is triangular and nilpotent. These conditions are satisfied for several classes of matrices, including Toeplitz, block Toeplitz, Hankel, and block Hankel, and for matrices whose blocks have such structure. Fast Cholesky factorization enables fast solution of least squares problems, total least squares problems, and regularized total least squares problems involving these classes of matrices. PMID- 27274923 TI - Projections Onto Order Simplexes and Isotonic Regression. AB - Isotonic regression is the problem of fitting data to order constraints. This problem can be solved numerically in an efficient way by successive projections onto order simplex constraints. An algorithm for solving the isotonic regression using successive projections onto order simplex constraints was originally suggested and analyzed by Grotzinger and Witzgall. This algorithm has been employed repeatedly in a wide variety of applications. In this paper we briefly discuss the isotonic regression problem and its solution by the Grotzinger Witzgall method. We demonstrate that this algorithm can be appropriately modified to run on a parallel computer with substantial speed-up. Finally we illustrate how it can be used to pre-process mass spectral data for automatic high throughput analysis. PMID- 27274924 TI - Three Rings of Polyhedral Simple Functions. AB - We survey three ways to multiply elements of the additive subgroup of the group of real-valued functions on R(d) which is generated by the indicator functions of polyhedra. In the resulting commutative rings, identities often correspond to useful techniques of decomposition of polyhedra. We are led immediately to various interesting topics, including Ehrhart polynomials, mixed volumes, Gram's relation, and transversal characteristics. PMID- 27274925 TI - Analysis of Interior-Point Paths. AB - Infeasible-interior-point paths are the main tools in interior-point methods for solving many kinds of optimization problems. These paths are usually parametrized by a penalty-parameter r ? 0 and further parameters describing their off centrality and infeasiblilty. Starting with an early result of C. Witzgall et al. [12] in linear programming, this paper gives an overview on results concerning the existence of these paths, their analyticity and the limiting behavior of their derivatives as r ? 0, and this also for degenerate problems in the areas of linear programming, linear complementarity problems, and semi-definte programming. PMID- 27274926 TI - Evaluation of Aerodynamic Drag and Torque for External Tanks in Low Earth Orbit. AB - A numerical procedure is described in which the aerodynamic drag and torque in low Earth orbit are calculated for a prototype Space Shuttle external tank and its components, the "LO2" and "LH2" tanks, carrying liquid oxygen and hydrogen, respectively, for any given angle of attack. Calculations assume the hypersonic limit of free molecular flow theory. Each shell of revolution is assumed to be described by a series of parametric equations for their respective contours. It is discretized into circular cross sections perpendicular to the axis of revolution, which yield a series of ellipses when projected according to the given angle of attack. The drag profile, that is, the projection of the entire shell is approximated by the convex envelope of those ellipses. The area of the drag profile, that is, the drag area, and its center of area moment, that is, the drag center, are then calculated and permit determination of the drag vector and the eccentricity vector from the center of gravity of the shell to the drag center. The aerodynamic torque is obtained as the cross product of those vectors. The tanks are assumed to be either evacuated or pressurized with a uniform internal gas distribution: dynamic shifting of the tank center of mass due to residual propellant sloshing is not considered. PMID- 27274927 TI - A Column-Generation and Branch-and-Cut Approach to the Bandwidth-Packing Problem. AB - The telecommunications problem of assigning calls with point to point demand to a capacitated network where each call can be assigned to at most one path has been called the Bandwidth-Packing Problem. For a given network, with specified arc costs and arc capacities, one wishes to route calls (defined by a starting and ending point) through the network to maximize the profit from the calls routed. Each such call is single path routed and not all calls will be routed. We propose a branch-and-cut methodology coupled with column generation to optimally solve such problems. We examine the alternative approaches in the literature and explain how this new method takes the best of all components of methods suggested previously. The method we suggest is new in that it includes a linear programming based heuristic for obtaining good lower bounds, uses lifted minimal covers that take into account special-ordered set constraints, and dynamically choose among three alternative branching strategies. In addition, whenever a new column is generated, it is lifted into all existing cuts. We also discuss the need to generate all tied optimal linear optimization solutions if one wishes to assure that the solution obtained is optimal. Our computational results provide solutions to problems previously unsolvable. PMID- 27274928 TI - RM 8111: Development of a Prototype Linewidth Standard. AB - Staffs of the Semiconductor Electronics Division, the Information Technology Laboratory, and the Precision Engineering Laboratory at NIST, have developed a new generation of prototype Single-Crystal CD (Critical Dimension) Reference (SCCDRM) Materials with the designation RM 8111. Their intended use is calibrating metrology instruments that are used in semiconductor manufacturing. Each reference material is configured as a 10 mm * 11 mm silicon test-structure chip that is mounted in a 200 mm silicon carrier wafer. The fabrication of both the chip and the carrier wafer uses the type of lattice-plane-selective etching that is commonly employed in the fabrication of micro electro-mechanical systems devices. The certified CDs of the reference features are determined from Atomic Force Microscope (AFM) measurements that are referenced to high-resolution transmission-electron microscopy images that reveal the cross-section counts of lattice planes having a pitch whose value is traceable to the SI meter. PMID- 27274929 TI - Requirements for the Development of Bacillus Anthracis Spore Reference Materials Used to Test Detection Systems. AB - Bacillus anthracis spores have been used as biological weapons and the possibility of their further use requires surveillance systems that can accurately and reliably detect their presence in the environment. These systems must collect samples from a variety of matrices, process the samples, and detect the spores. The processing of the sample may include removal of inhibitors, concentration of the target, and extraction of the target in a form suitable for detection. Suitable reference materials will allow the testing of each of these steps to determine the sensitivity and specificity of the detection systems. The development of uniform and well-characterized reference materials will allow the comparison of different devices and technologies as well as assure the continued performance of detection systems. This paper discusses the special requirements of reference materials for Bacillus anthracis spores that could be used for testing detection systems. The detection of Bacillus anthracis spores is based on recognition of specific characteristics (markers) on either the spore surface or in the nucleic acids (DNA). We have reviewed the specific markers and their relevance to characterization of reference materials. We have also included the approach for the characterization of candidate reference materials that we are developing at the NIST laboratories. Additional applications of spore reference materials would include testing sporicidal treatments, techniques for sampling the environment, and remediation of spore-contaminated environments. PMID- 27274930 TI - Variable Magnification With Kirkpatrick-Baez Optics for Synchrotron X-Ray Microscopy. AB - We describe the distinction between the operation of a short focal length x-ray microscope forming a real image with a laboratory source (convergent illumination) and with a highly collimated intense beam from a synchrotron light source (Kohler illumination). We demonstrate the distinction with a Kirkpatrick Baez microscope consisting of short focal length multilayer mirrors operating at an energy of 8 keV. In addition to realizing improvements in the resolution of the optics, the synchrotron radiation microscope is not limited to the usual single magnification at a fixed image plane. Higher magnification images are produced by projection in the limit of geometrical optics with a collimated beam. However, in distinction to the common method of placing the sample behind the optical source of a diverging beam, we describe the situation in which the sample is located in the collimated beam before the optical element. The ultimate limits of this magnification result from diffraction by the specimen and are determined by the sample position relative to the focal point of the optic. We present criteria by which the diffraction is minimized. PMID- 27274931 TI - Simulating Timescale Dynamics of Network Traffic Using Homogeneous Modeling. AB - Simulating and understanding traffic dynamics in large networks are difficult and challenging due to the complexity of such networks and the limitations inherent in simulation modeling. Typically, simulation models used to study traffic dynamics include substantial detail representing protocol mechanisms across several layers of functionality. Such models must be restricted in space and time in order to be computationally tractable. We propose an alternative simulation approach that uses homogeneous modeling with an increased level of abstraction, in order to explore networks at larger space-time scales than otherwise feasible and to develop intuition and insight about the space-time dynamics of large networks. To illustrate the utility of our approach, we examine some current understandings of the timescale dynamics of network traffic, and we discuss some speculative results obtained with homogeneous modeling. Using a wavelet-based technique, we show correlation structures, and changes in correlation structures, of network traffic under variations in traffic sources, transport mechanisms, and network structure. Our simulation results justify further investigation of our approach, which might benefit from cross-verifications against more detailed simulation models. PMID- 27274933 TI - Erratum: External-Field Shifts of the (199)Hg(+) Optical Frequency Standard. AB - [This corrects the article on p. 829 in vol. 105.]. PMID- 27274932 TI - Simple Thermal-Efficiency Model for CMOS-Microhotplate Design. AB - Simple, semi-empirical, first-order, analytic approximations to the current, voltage, and power as a function of microhotplate temperature are derived. To lowest order, the voltage is independent of, and the power and current are inversely proportional to, the length of the microhotplate heater legs. A first order design strategy based on this result is described. PMID- 27274934 TI - Measurement of 100 nm and 60 nm Particle Standards by Differential Mobility Analysis. AB - The peak particle size and expanded uncertainties (95 % confidence interval) for two new particle calibration standards are measured as 101.8 nm +/- 1.1 nm and 60.39 nm +/- 0.63 nm. The particle samples are polystyrene spheres suspended in filtered, deionized water at a mass fraction of about 0.5 %. The size distribution measurements of aerosolized particles are made using a differential mobility analyzer (DMA) system calibrated using SRM((r)) 1963 (100.7 nm polystyrene spheres). An electrospray aerosol generator was used for generating the 60 nm aerosol to almost eliminate the generation of multiply charged dimers and trimers and to minimize the effect of non-volatile contaminants increasing the particle size. The testing for the homogeneity of the samples and for the presence of multimers using dynamic light scattering is described. The use of the transfer function integral in the calibration of the DMA is shown to reduce the uncertainty in the measurement of the peak particle size compared to the approach based on the peak in the concentration vs. voltage distribution. A modified aerosol/sheath inlet, recirculating sheath flow, a high ratio of sheath flow to the aerosol flow, and accurate pressure, temperature, and voltage measurements have increased the resolution and accuracy of the measurements. A significant consideration in the uncertainty analysis was the correlation between the slip correction of the calibration particle and the measured particle. Including the correlation reduced the expanded uncertainty from approximately 1.8 % of the particle size to about 1.0 %. The effect of non-volatile contaminants in the polystyrene suspensions on the peak particle size and the uncertainty in the size is determined. The full size distributions for both the 60 nm and 100 nm spheres are tabulated and selected mean sizes including the number mean diameter and the dynamic light scattering mean diameter are computed. The use of these particles for calibrating DMAs and for making deposition standards to be used with surface scanning inspection systems is discussed. PMID- 27274935 TI - Methods to Characterize Ricin for the Development of Reference Materials. AB - Ricin is an abundant protein from the castor bean plant Ricinus communis. Because of its high toxicity and the simplicity of producing mass quantities, ricin is considered a biological terrorism agent. We have characterized ricin extensively with a view to develop Reference Materials that could be used to test and calibrate detection devices. The characterization of ricin includes: 1) purity test of a commercial batch of ricin using electrophoresis in polyacrylamide gels, 2) biological activity assay by measuring its ability to inhibit protein synthesis, 3) quantitation of protein concentration by amino acid analysis, 4) detection of ricin by an immunoassay using a flow cytometer, and 5) detection of ricin genomic DNA by polymerase chain reaction using nine different primer sets. By implementing these five methods of characterization, we are in a position to develop a reference material for ricin. PMID- 27274936 TI - Intercomparison of the LBIR Absolute Cryogenic Radiometers to the NIST Optical Power Measurement Standard. AB - The Low Background Infrared calibration (LBIR) facility at the National Institute of Standards and Technology (NIST) presently maintains four absolute cryogenic radiometers (ACRs) which serve as standard reference detectors for infrared calibrations performed by the facility. The primary standard for optical power measurements at NIST-Gaithersburg has been the High Accuracy Cryogenic Radiometer (HACR). Recently, an improved radiometer, the Primary Optical Watt Radiometer (POWR), has replaced the HACR as the primary standard. In this paper, we present the results of comparisons between the radiometric powers measured by the four ACRs presently maintained by the LBIR facility to that measured by the HACR and POWR. This was done by using a Si photodiode light-trapping detector as a secondary transfer standard to compare the primary national standards to the ACRs maintained by the LBIR facility. The technique used to compare an ACR to the trap detector is described in detail. The absolute optical power measurements are found to be within 0.1 % of the primary standard for all the ACRs examined in this study. PMID- 27274937 TI - Development of Argon Isotope Reference Standards for the U.S. Geological Survey. AB - The comparison of physical ages of geological materials measured by laboratories engaged in geochronological studies has been limited by the accuracy of mineral standards or monitors for which reported ages have differed by as much as 2 %. In order to address this problem, the U.S. Geological Survey is planning to calibrate the conventional (40)Ar/(40)K age of a new preparation of an international hornblende standard labeled MMhb-2. The (40)K concentration in MMhb 2 has already been determined by the Analytical Chemistry Division at NIST with an uncertainty of 0.2 %. The (40)Ar concentration will be measured by the USGS using the argon isotope reference standards that were recently developed by NIST and are described in this paper. The isotope standards were constructed in the form of pipette/reservoir systems and calibrated by gas expansion techniques to deliver small high-precision aliquots of high-purity argon. Two of the pipette systems will deliver aliquots of (38)Ar having initial molar quantities of 1.567 * 10(-10) moles and 2.313 * 10(-10) moles with expanded (k = 2) uncertainties of 0.058 % and 0.054 %, respectively. Three other pipette systems will deliver aliquots (nominally 4 * 10(-10) moles) of (40)Ar:(36)Ar artificial mixtures with similar accuracy and with molar ratios of 0.9974 +/- 0.06 %, 29.69 +/- 0.06 %, and 285.7 +/- 0.08 % (k = 2). These isotope reference standards will enable the USGS to measure the (40)Ar concentration in MMhb-2 with an expanded uncertainty of ~ 0.1 %. In the process of these measurements, the USGS will re-determine the isotopic composition of atmospheric Ar and calculate a new value for its atomic weight. Upon completion of the USGS calibrations, the MMhb-2 mineral standard will be certified by NIST for its K and Ar concentrations and distributed as a Standard Reference Material (SRM). The new SRM and the NIST-calibrated transportable pipette systems have the potential for dramatically improving the accuracy of interlaboratory calibrations and thereby the measured ages of geological materials, by as much as a factor of ten. PMID- 27274938 TI - Normalization and Technical Variation in Gene Expression Measurements. AB - Using data from the Microarray Quality Control (MAQC) project, we demonstrate two data-analysis methods that shed light on the normalization of gene expression measurements and thereby on their technical variation. One is an improved method for normalization of multiple assays with mRNA concentrations related by a parametric model. The other is a method for characterizing limitations on the effectiveness of normalization in reducing technical variation. We apply our improved normalization to the four project materials as part of testing the linearity of the probe responses. We find that the lack of linearity is statistically significant but small enough that its sources cannot be easily identified. Applying our characterization method to assays of the same material, we show that there is a source of variation that cannot be eliminated by normalization and therefore must be dealt with by other means. Four high-density, single probe, one-color microarray platforms underlie our demonstration. PMID- 27274940 TI - Comparison of the NIST and BIPM Standards for Air Kerma in Medium-Energy X-Rays. AB - A comparison has been made of the air-kerma standards for medium-energy x-rays of the National Institute of Standards and Technology (NIST) and the Bureau International des Poids et Mesures (BIPM). The comparison involved a series of measurements at the BIPM and the NIST using the air-kerma standards and three NIST reference-class transfer ionization chamber standards. Reference beam qualities in the range from 100 kV to 250 kV were used. The results show the standards to be in reasonable agreement within the combined standard uncertainty of the comparison of 0.37 %, although a significant trend with radiation quality is observed and the possible sources discussed. PMID- 27274939 TI - Form-Profiling of Optics Using the Geometry Measuring Machine and the M-48 CMM at NIST. AB - We are developing an instrument, the Geometry Measuring Machine (GEMM), to measure the profile errors of aspheric and free form optical surfaces, with measurement uncertainties near 1 nm. Using GEMM, an optical profile is reconstructed from local curvatures of a surface, which are measured at points on the optic's surface. We will describe a prototype version of GEMM, its repeatability with time, a measurements registry practice, and the calibration practice needed to make nanometer resolution comparisons with other instruments. Over three months, the repeatability of GEMM is 3 nm rms, and is based on the constancy of the measured profile of an elliptical mirror with a radius of curvature of about 83 m. As a demonstration of GEMM's capabilities for curvature measurement, profiles of that same mirror were measured with GEMM and the NIST Moore M-48 coordinate measuring machine. Although the methods are far different, two reconstructed profiles differ by 22 nm peak-to-valley, or 6 nm rms. This comparability clearly demonstrates that with appropriate calibration, our prototype of the GEMM can measure complex-shaped optics. PMID- 27274942 TI - Spectrally Tunable Sources for Advanced Radiometric Applications. AB - A common radiometric platform for the development of application-specific metrics to quantify the performance of sensors and systems is described. Using this platform, sensor and system performance may be quantified in terms of the accuracy of measurements of standardized sets of source distributions. The prototype platform consists of spectrally programmable light sources that can generate complex spectral distributions in the ultraviolet, visible and short wave infrared regions for radiometric, photometric and colorimetric applications. In essence, the programmable spectral source is a radiometric platform for advanced instrument characterization and calibration that can also serve as a basis for algorithm testing and instrument comparison. PMID- 27274941 TI - Ambiguities in Powder Indexing: the Impact of a Quaternary Lattice Metric Singularity on the Characterization of Mawsonite and Chatkalite. AB - A lattice metric singularity occurs when unit cells defining two (or more) lattices yield the identical set of unique calculated d-spacings. The minerals Mawsonite and Chatkalite are of especial interest as both are characterized by tetragonal unit cells that correspond to the second member of a quaternary lattice metric singularity. This singularity includes lattices that are Cubic I, Tetragonal P, Orthorhombic F, and Orthorhombic P. The Mawsonite and Chatkalite lattices are unique in that they are highly specialized. In each case: (1) the determinative c/a ratio is very near 1/?2, (2) the symmetrical scalars of the reduced form [ a . a : b . b : c . c = 1:2:2] have greater specialization than required for the given reduced form type, (3) the tetragonal lattice has derivative lattices of higher symmetry, and (4) the powder pattern is highly compressed. Mawsonite and Chatkalite serve as exemplar-type compounds. Their tetragonal structure has important implications in structure determination using powder diffraction data. First, any cubic I lattice - established solely on the basis of indexing procedures - may actually be tetragonal or orthorhombic. Second, in establishing the lattice of an unknown, results from powder data indexing require routine confirmation by other techniques (e.g., single crystal, optical, etc.). PMID- 27274943 TI - Bayesian Tomography for Projections with an Arbitrary Transmission Function with an Application in Electron Microscopy. AB - The vast majority of the developments in tomography assume that the transmission of the probe through the sample follows Beer's Law, i.e., the rule of exponential attenuation. However, for transmission electron microscopy of samples a few times their mean free path, Beer's Law is no longer an accurate description of the transmission of the probe as a function of the sample thickness. Recent simulations [Z. H. Levine, Appl. Phys. Lett. 82, 3943 (2003)] have demonstrated accounting for the correct transmission function leads to superior tomographic reconstructions for a photonic band gap sample 8 um square. Those recent simulations assumed that data was available at all angles, i.e., over 180 degrees . Here, we consider a limited-angle case by generalizing the Bayesian formalism of Bouman and Sauer to allow an arbitrary transmission function. The new formalism is identical to that of Bouman and Sauer when the transmission function obeys Beer's Law. The examples, based on 140 degrees of data, suggest that using the physical transmission function is a requirement for performing limited angle reconstructions. PMID- 27274944 TI - NIST Calibration of a Neutron Spectrometer ROSPEC. AB - A neutron spectrometer was acquired for use in the measurement of National Institute of Standards and Technology neutron fields. The spectrometer included options for the measurement of low and high energy neutrons, for a total measurement range from 0.01 eV up to 17 MeV. The spectrometer was evaluated in calibration fields and was used to determine the neutron spectrum of an Americium Beryllium neutron source. The calibration fields used included bare and moderated (252)Cf, monoenergetic neutron fields of 2.5 MeV and 14 MeV, and a thermal neutron beam. Using the calibration values determined in this exercise, the spectrometer gives a good approximation of the neutron spectrum, and excellent values for neutron fluence, for all NIST calibration fields. The spectrometer also measured an Americium-Beryllium neutron field in a NIST exposure facility and determined the field quite well. The spectrometer measured scattering effects in neutron spectra which previously could be determined only by calculation or integral measurements. PMID- 27274945 TI - Synthetic Incoherence via Scanned Gaussian Beams. AB - Tomography, in most formulations, requires an incoherent signal. For a conventional transmission electron microscope, the coherence of the beam often results in diffraction effects that limit the ability to perform a 3D reconstruction from a tilt series with conventional tomographic reconstruction algorithms. In this paper, an analytic solution is given to a scanned Gaussian beam, which reduces the beam coherence to be effectively incoherent for medium size (of order 100 voxels thick) tomographic applications. The scanned Gaussian beam leads to more incoherence than hollow-cone illumination. PMID- 27274946 TI - In-situ Attenuation Corrections for Radiation Force Measurements of High Frequency Ultrasound With a Conical Target. AB - Radiation force balance (RFB) measurements of time-averaged, spatially-integrated ultrasound power transmitted into a reflectionless water load are based on measurements of the power received by the RFB target. When conical targets are used to intercept the output of collimated, circularly symmetric ultrasound sources operating at frequencies above a few megahertz, the correction for in situ attenuation is significant, and differs significantly from predictions for idealized circumstances. Empirical attenuation correction factors for a 45 degrees (half-angle) absorptive conical RFB target have been determined for 24 frequencies covering the 5 MHz to 30 MHz range. They agree well with previously unpublished attenuation calibration factors determined in 1994 for a similar target. PMID- 27274947 TI - Recollections on Sixty Years of NBS Ionizing Radiation Programs for Energetic X Rays and Electrons. AB - These recollections are on ionizing radiation programs at the National Bureau of Standards (NBS) that started in 1928 and ended in 1988 when NBS became the National Institute of Standards and Technology (NIST). The independent Council on Ionizing Radiation Measurements and Standards (CIRMS) was formed in 1992. This article focuses on how measurements and standards for x rays, gamma rays, and electrons with energies above 1 MeV began at NBS and how they progressed. It also suggests how the radiation processors of materials and foods, the medical radiographic and radiological industries, and the radiological protection interests of the government (including homeland security) represented in CIRMS can benefit from NIST programs. PMID- 27274948 TI - Erratum: Noise-Parameter Uncertainties: A Monte Carlo Simulation. AB - [This corrects the article on p. 433 in vol. 107.]. PMID- 27274950 TI - Cellulose, Chitosan and Keratin Composite Materials: Facile and Recyclable Synthesis, Conformation and Properties. AB - A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites formed to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl-]), an ionic liquid, was used as the sole solvent, and because the majority of [BMIm+Cl-] used (at least 88%) was recovered, the method is green and recyclable. FTIR, XRD, 13C CP-MAS NMR and SEM results confirm that KER, CS and CEL remain chemically intact and distributed homogeneously in the composites. We successfully demonstrate that the widely used method based on the deconvolution of the FTIR bands of amide bonds to determine secondary structure of proteins is relatively subjective as the conformation obtained is strongly dependent on the choice of parameters selected for curve fitting. A new method, based on the partial least squares regression analysis (PLSR) of the amide bands, was developed, and proven to be objective and can provide more accurate information. Results obtained with this method agree well with those by XRD, namely they indicate that although KER retains its second structure when incorporated into the [CEL+CS] composites, it has relatively lower alpha-helix, higher beta-turn and random form compared to that of the KER in native wool. It seems that during dissolution by [BMIm+Cl-], the inter- and intramolecular forces in KER were broken thereby destroying its secondary structure. During regeneration, these interactions were reestablished to reform partially the secondary structure. However, in the presence of either CEL or CS, the chains seem to prefer the extended form thereby hindering reformation of the alpha-helix. Consequently, the KER in these matrices may adopt structures with lower content of alpha-helix and higher beta-sheet. As anticipated, results of tensile strength and TGA confirm that adding CEL or CS into KER substantially increase the mechanical strength and thermal stability of the [CS/CEL+KER] composites. PMID- 27274949 TI - Spontaneous Eye-Blink Rate as an Index of Reward Responsivity: Validation and Links to Bipolar Disorder. AB - Extensive research supports the role of striatal dopamine in pursuing and responding to reward, and that eye-blink rate is a valid indicator of striatal dopamine. This study tested whether phasic changes in blink rate could provide an index of reward pursuit. This hypothesis was tested in people with bipolar I disorder (BD; a population with aberrations in reward responsivity), and in those without BD. Thirty-one adults with BD and 28 control participants completed a laboratory task involving effort towards monetary reward. Blink rate was recorded using eye-tracking at baseline, reward anticipation, and post-reward. Those in the BD group completed self-report measures relating to reward and ambition. Results showed that across all participants, blink rates increased from reward anticipation to post-reward. In the BD group, reward-relevant measures were strongly correlated with variation in blink rate. These findings provide validation for phasic changes in blink rate as an index of reward response. PMID- 27274951 TI - A Comparative Review of Waivers Granted in Pediatric Drug Development by FDA and EMA from 2007-2013. AB - BACKGROUND: The European Union and the United States have different legal frameworks in place for pediatric drug development, which can potentially lead to different pediatric research requirements for the pharmaceutical industry. This manuscript compares pediatric clinical trial waivers granted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). METHODS: This is a retrospective review comparing EMA's Paediatric Committee (PDCO) decisions with FDA's Pediatric Review Committee (PeRC) recommendations for all product-specific pediatric full waiver applications submitted to EMA from January 2007 through December 2013. Using baseline data from EMA, we matched product specific waivers with their FDA equivalents during the study period. RESULTS: For single active substance products, PDCO and PeRC adopted similar opinions in 42 of 49 indications (86%). For fixed-dose combinations, PDCO and PeRC adopted similar opinions in 24 of 31 indications (77%). CONCLUSION: Despite the different legal frameworks, criteria, and processes of determination, the waiver decisions of the 2 agencies were similar in the majority of cases. PMID- 27274952 TI - References for Haplotype Imputation in the Big Data Era. AB - Imputation is a powerful in silico approach to fill in those missing values in the big datasets. This process requires a reference panel, which is a collection of big data from which the missing information can be extracted and imputed. Haplotype imputation requires ethnicity-matched references; a mismatched reference panel will significantly reduce the quality of imputation. However, currently existing big datasets cover only a small number of ethnicities, there is a lack of ethnicity-matched references for many ethnic populations in the world, which has hampered the data imputation of haplotypes and its downstream applications. To solve this issue, several approaches have been proposed and explored, including the mixed reference panel, the internal reference panel and genotype-converted reference panel. This review article provides the information and comparison between these approaches. Increasing evidence showed that not just one or two genetic elements dictate the gene activity and functions; instead, cis interactions of multiple elements dictate gene activity. Cis-interactions require the interacting elements to be on the same chromosome molecule, therefore, haplotype analysis is essential for the investigation of cis-interactions among multiple genetic variants at different loci, and appears to be especially important for studying the common diseases. It will be valuable in a wide spectrum of applications from academic research, to clinical diagnosis, prevention, treatment, and pharmaceutical industry. PMID- 27274953 TI - Orderly Steps in Progression of JC Virus to Virulence in the Brain. AB - Progressive multifocal leukoencephalopathy is a neurodegenerative disease caused by demyelination in the brain. The demyelination is due to infection of oligodendroglial cells by polyomavirus JC, a circular DNA virus. The virus resides as an archetype form in uroepithelial cells and bone marrow of more than 70% of adults, in whom it seldom causes overt symptoms. The JC viral form infecting the brain differs from the archetype. This viral form contains two deletions and a duplication in the non-coding control region that are thought to be derived from the archetype. These rearrangements are necessary for neurovirulence. This review considers how these rearrangements occur in the context of transit to the brain and adaptation to infect glial cells. PMID- 27274954 TI - Treatment considerations for patient with Amelogenesis Imperfecta: a review. AB - Amelogenesis imperfecta (AI) is a group of inherited disorders primary affecting the structural of enamel. Patients with AI experience poor esthetic, excessive tooth sensitivity and compromised chewing function that dental treatments are frequently required at early age. This review describes the non-enamel implications, stage-specific management strategies and outcomes of selected restorative materials based on literature evidence. PMID- 27274955 TI - Did John B. Watson Really "Found" Behaviorism? AB - Developments culminating in the nineteenth century, along with the predictable collapse of introspective psychology, meant that the rise of behavioral psychology was inevitable. In 1913, John B. Watson was an established scientist with impeccable credentials who acted as a strong and combative promoter of a natural science approach to psychology when just such an advocate was needed. He never claimed to have founded "behavior psychology" and, despite the acclaim and criticism attending his portrayal as the original behaviorist, he was more an exemplar of a movement than a founder. Many influential writers had already characterized psychology, including so-called mental activity, as behavior, offered many applications, and rejected metaphysical dualism. Among others, William Carpenter, Alexander Bain, and (early) Sigmund Freud held views compatible with twentieth-century behaviorism. Thus, though Watson was the first to argue specifically for psychology as a natural science, behaviorism in both theory and practice had clear roots long before 1913. If behaviorism really needs a "founder," Edward Thorndike might seem more deserving, because of his great influence and promotion of an objective psychology, but he was not a true behaviorist for several important reasons. Watson deserves the fame he has received, since he first made a strong case for a natural science (behaviorist) approach and, importantly, he made people pay attention to it. PMID- 27274956 TI - Contingency Horizon: on Private Events and the Analysis of Behavior. AB - Skinner's radical behaviorism incorporates private events as biologically based phenomena that may play a functional role with respect to other (overt) behavioral phenomena. Skinner proposed four types of contingencies, here collectively termed the contingency horizon, which enable certain functional relations between private events and verbal behavior. The adequacy and necessity of this position has met renewed challenges from Rachlin's teleological behaviorism and Baum's molar behaviorism, both of which argue that all "mental" phenomena and terminology may be explained by overt behavior and environment behavior contingencies extended in time. A number of lines of evidence are presented in making a case for the functional characteristics of private events, including published research from behavior analysis and general experimental psychology, as well as verbal behavior from a participant in the debate. An integrated perspective is offered that involves a multiscaled analysis of interacting public behaviors and private events. PMID- 27274957 TI - Gamification: The Intersection between Behavior Analysis and Game Design Technologies. AB - Deterding et al. (Proceedings of the 15th International Academic MindTrek Conference: Envisioning Future Media Environments, USA 15: 9-15, 2011) report a recent rise in popularity of video game inspired software designed to address issues in a variety of areas, including health, energy conservation, education, and business. These applications have been based on the concept of gamification, which involves a process by which nongame activities are designed to be more like a game. We provide examples of how gamification has been used to increase health related behavior, energy consumption, academic performance, and other socially significant behavior. We argue that behavior analytic research and practice stands to benefit from incorporating successful elements of game design. Lastly, we provide suggestions for behavior analysts regarding applied and basic research related to gamification. PMID- 27274958 TI - The Evidence-Based Practice of Applied Behavior Analysis. AB - Evidence-based practice (EBP) is a model of professional decision-making in which practitioners integrate the best available evidence with client values/context and clinical expertise in order to provide services for their clients. This framework provides behavior analysts with a structure for pervasive use of the best available evidence in the complex settings in which they work. This structure recognizes the need for clear and explicit understanding of the strength of evidence supporting intervention options, the important contextual factors including client values that contribute to decision making, and the key role of clinical expertise in the conceptualization, intervention, and evaluation of cases. Opening the discussion of EBP in this journal, Smith (The Behavior Analyst, 36, 7-33, 2013) raised several key issues related to EBP and applied behavior analysis (ABA). The purpose of this paper is to respond to Smith's arguments and extend the discussion of the relevant issues. Although we support many of Smith's (The Behavior Analyst, 36, 7-33, 2013) points, we contend that Smith's definition of EBP is significantly narrower than definitions that are used in professions with long histories of EBP and that this narrowness conflicts with the principles that drive applied behavior analytic practice. We offer a definition and framework for EBP that aligns with the foundations of ABA and is consistent with well-established definitions of EBP in medicine, psychology, and other professions. In addition to supporting the systematic use of research evidence in behavior analytic decision making, this definition can promote clear communication about treatment decisions across disciplines and with important outside institutions such as insurance companies and granting agencies. PMID- 27274959 TI - Publishing Outside the Box: Popular Press Books. AB - Writing and publishing popular press books requires a set of skills, not natural to basic and applied researchers trained to publish in peer-referred behavior analytic journals or to practice behavior analysis in applied settings. This article provides suggestions and examples. These include finding a distinctive idea, securing a contract, hiring an agent (or not), deciding on a publisher, and writing engagingly for a broad audience. The last is the greatest challenge. Among my recommendations are to read good prose, good models, and good books about publishing; talk to experienced colleagues; read aloud to judge the appropriateness of your vocabulary and style; and interject humor, imagery, and drama. Book publishing is a long and difficult process, but it is possible. It has a great potential for bringing behavior analytic research, practice and theory to the attention of the general public. PMID- 27274961 TI - Publishing Outside the Box: Unforeseen Dividends of Talking to Strangers. AB - This article describes publishing outside behavior analysis, letters to editors, and columns, as well as communicating outside the box with editors, authors, and journalists. Publishing can occur in a wide range of journals (e.g., Consciousness and Cognition), in-house publications of professional associations (e.g., Association for Psychological Science's Observer), general science publications (e.g., American Scientist, The Scientist), publications in service to professions (e.g., The Chronicle of Higher Education), general interest and specialized magazines (e.g., Atlantic Monthly, Skeptical Inquirer), and newspapers (e.g., Los Angeles Times). Communicating with editors, authors, and journalists includes, for instance, formal correspondence with editors and personal correspondence with authors and journalists outside the box about misunderstandings, commonalities, and complementarities of their work with respect to ours. The consequences of publishing and communicating are often unforeseen and fortuitous, many of which can never occur by remaining in the box. PMID- 27274960 TI - Publishing in Journals Outside the Box: Attaining Mainstream Prominence Requires Demonstrations of Mainstream Relevance. AB - Primary pediatric medical care is as mainstream as any major cultural practice in the USA. Thus, publishing behavior analytic papers that pertain to problems that present in pediatric settings in pediatric medical journals is one route to mainstream relevance. With sufficient numbers of such papers, it could even lead to prominence. This article describes examples of publishing in pediatric journals and some lessons I learned from the experience. For example, (1) all child behavior problems that present in pediatric settings are of social importance but most are high-frequency, low-intensity problems that are not necessarily exotic or representative of serious pathology, and they usually respond to straightforward behavioral applications; (2) it is usually best to use a "colloquialized version of learning theory" when writing for and speaking to pediatric providers (and the families for whom they provide care); (3) pediatricians often have limited knowledge about behavior analytic research designs; and (4) when submissions are rejected by pediatric journals, the rejection can be exploited as an opportunity to educate pediatric editors and reviewers. PMID- 27274962 TI - Determining How, When, and Whether You Should Publish Outside the Box: Sober Advice for Early Career Behavior Analysts. AB - Publishing outside of behavior analysis is necessary for the field's impact in advancing its science or improving its treatments. As consumers of behavior analysis, we typically only see the success stories in outlets such as the Journal for the Experimental Analysis of Behavior, the Journal of Applied Behavior Analysis, and The Behavior Analyst. Lacking from these models is a description of the hard work and occasional missteps that accompany dissemination outside the box. In this paper, I propose that prospective disseminators need to (a) critically evaluate what they have to say, (b) carefully consider the field's interests, and (c) honestly analyze professional and personal contingencies to determine whether publishing outside the box should be a priority, depending on one's stage of professional development. I conclude with some general recommendations to early career behavior analysts aspiring to disseminate outside the field. PMID- 27274963 TI - Stop Preaching to the Choir, Publish Outside the Box: A Discussion. AB - In this article, I comment on Normand's, Vyse's, Friman's, Schlinger's, and Reed's articles on publishing books, journal articles, letters to the editor, and columns outside of behavior analysis, that is, "outside the box," as well as communicating with editors, authors, and journalists. Among the topics I address are the prerequisite repertoires and these authors' guidance (e.g., task analyses), as well as technical terms and language and the many opportunities available to us, yet also caveats about how, whether, and when we should publish outside the box. In the process, I include lessons I have learned from submitting my own manuscripts outside the box and suggestions I have gleaned from my failures and successes. In conclusion, if the field values publishing outside the box, then, it should analyze the necessary repertoires and provide systematic instruction in them. PMID- 27274964 TI - Nu-Way Snaps and Snap Leads: an Important Connection in the History of Behavior Analysis. AB - Beginning in the early 1950s, the snap lead became an integral and ubiquitous component of the programming of electromechanical modules used in behavioral experiments. It was composed of a Nu-Way snap connector on either end of a colored electrical wire. Snap leads were used to connect the modules to one another, thereby creating the programs that controlled contingencies, arranged reinforcers, and recorded behavior in laboratory experiments. These snap leads populated operant conditioning laboratories from their inception until the turn of the twenty-first century. They allowed quick and flexible programming because of the ease with which they could be connected, stacked, and removed. Thus, the snap lead was integral to the research activity that constituted the experimental analysis of behavior for more than five decades. This review traces the history of the snap lead from the origins of the snap connector in Birmingham, England, in the late eighteenth century, through the use of snaps connected to wires during the Second World War, to its adoption in operant laboratories, and finally to its demise in the digital age. PMID- 27274965 TI - Behavior Analysts to the Front! A 15-Step Tutorial on Public Speaking. AB - Mainstream prominence was Skinner's vision for behavior analysis. Unfortunately, it remains elusive, even as we approach the 110th anniversary of his birth. It can be achieved, however, and there are many routes. One that seems overlooked in many (most?) behavior analytic training programs is what I call the front of the room. The front of the room is a very powerful locus for influencing people. Mastering it can turn a commoner into a king; a middling man into a mayor; or a group of disorganized, dispirited people into an energized force marching into battle. The most powerful members of our species had their most memorable moments at the front of the room. If so much is available there, why is mastery of it in such short supply, not just in behavior analysts but in the population at large? In this paper, I address why, argue that the primary reason can be overcome, and supply 15 behaviorally based steps to take in pursuit of front of the room mastery. PMID- 27274966 TI - Improving the Conversational Skills of a College Student with Peer-Mediated Behavioral Skills Training. AB - We used a multiple baseline design across behaviors to evaluate peer-mediated behavioral skills training to improve a complex repertoire of conversational skills of an undergraduate student diagnosed with a learning disability NOS. Following treatment, we observed a decrease in interrupting and content specificity and an increase in questioning. Treatment effects maintained with naive peers during unstructured conversations and outcomes compared favorably with normative data on the conversational skills of three undergraduates without learning disabilities. PMID- 27274967 TI - Mands for Information Using "How" Under EO-Absent and EO-Present Conditions. AB - The present study replicates and extends previous research on teaching "How?" mands for information to children with autism. The experimental preparation involved mand training in the context of completing preferred activities and included training and testing under conditions when the establishing operation (EO) was present and absent. Results show that two children with autism acquired mands for information using How? only in situations where information was valuable (i.e., the EO was present); they then consistently made use of the information provided in activity completion. Generalization to novel, untaught situations was assessed. PMID- 27274968 TI - Observing Tacting Increases Uninstructed Tacts in Children with Autism. AB - The effects of observing an adult emitting tacts on children's rate of uninstructed (i.e., "spontaneous") tacts were examined in three children diagnosed with autism. Each participant was exposed to two conditions in four settings each: in condition 1, participants received 20 trials of teacher initiated interactions in which the child was asked to tact 20 objects during 5 min. Condition 2 was identical to condition 1 except that the teacher also tacted 20 objects interspersed with the 20 tact trials. The number of uninstructed tacts was recorded in both conditions. Children emitted between 1.58 and 2.68 times more uninstructed tacts in condition 2 than in condition 1. These results indicate that teachers' emission of tacts increases the emission of uninstructed tacts in children with autism. PMID- 27274969 TI - Teaching Tacting of Private Events Based on Public Accompaniments: Effects of Contingencies, Audience Control, and Stimulus Complexity. AB - Our current understanding of the role of private events in the science of behavior is based largely on Skinner's natural science interpretation of private events. Skinner described public accompaniments as one source of control for a verbal community to differentially reinforce verbal behavior regarding private events. In this study, we developed an experimental analogue to study variables influencing tacting of private events. The participant had exclusive access to one set of stimuli (the private stimuli), and the experimenter attempted to teach tacts for private stimuli based on their correspondence with public stimuli accessible to both the experimenter and participant. Results of experiments 1 and 2 demonstrated that reports of private stimuli were a function of degree of public-private correspondence, reinforcement contingency, and audience control. In some cases, we encountered reports controlled exclusively by public stimuli. Results of experiment 3 showed that public control was less likely when public stimuli were more complex and the experimenter had a unique behavioral history with respect to those stimuli that was not shared by the learner. The orderly patterns of data obtained suggest that analogue arrangements might be a useful, and even necessary, starting point for experimental investigations of how private events may enter into the analysis of behavior. PMID- 27274970 TI - The Effects of Contingent Caregiver Imitation of Infant Vocalizations: a Comparison of Multiple Caregivers. AB - The present study replicated and extended the Pelaez et al. (Journal of Applied Behavior Analysis 44:33-40, 2011) study, which examined the reinforcing effects of mothers' contingent imitation of their infants' vocalizations. Three infants aged 7-12 months who could vocalize sounds but not words participated with two caregivers for each infant (i.e., triads). During the intervention phase, the caregivers were asked to immediately imitate all vocalizations emitted by the child for a 3-min period. During the yoked control phase, the caregivers listened to an audio recording from the preceding condition and provided vocalizations non contingently on the infants' responses. The procedures yielded different results across participants; one infant emitted a higher frequency of vocalizations during the contingent imitation phases over the control phases, and the other two infants showed higher rates of responding during the control phases. However, all infants emitted more imitative return vocalizations during contingent reinforcement conditions compared with the yoked control condition. PMID- 27274971 TI - Establishing Concurrent Mands for Items and Mands for Information about Location in Children with Autism. AB - This study replicated and extended the methodology used in Howlett et al. (Journal of Applied Behavior Analysis, 44, 943-947 2011) to bring the mands "Where's (item)?" and "I want (item)" under appropriate antecedent control in two boys diagnosed with autism. Trials were alternated in which items were present, missing, and within view (but inaccessible) and missing and out of view. To program for generalization, fifteen items, multiple trainers, and multiple settings were used during teaching. For both participants, manding generalized to novel items, instructors, settings, and situations and maintained after 2 weeks following teaching. Results of the social validity assessment indicated that school staff found the procedures highly acceptable. PMID- 27274972 TI - Implementing the Verbal Behavior Milestones Assessment and Placement Program (VB MAPP): Teaching Assessment Techniques. AB - The Verbal Behavior Milestones Assessment and Placement Program (VB-MAPP) is an assessment tool used with individuals diagnosed with autism spectrum disorder and other language delays (Sundberg 2008). The milestones assessment section of the VB-MAPP is used to determine an individual's current skill level. The results of the milestones assessment can be used to identify instructional goals and objectives. The current study examined the effects of behavioral skills training (BST) on the administration of the milestones assessment by two educational professionals. The BST intervention resulted in immediate increases in performance for both participants. PMID- 27274973 TI - Stimulus-Stimulus Pairing of Vocalizations: A Systematic Replication. AB - The current study replicated an enhanced stimulus-stimulus pairing (SSP) procedure used by Esch et al. (Journal of Applied Behavior Analysis 42: 42-225, 2009) for increasing vocalizations in children with autism. The enhanced SSP procedure consisted of pairing target vocalizations with high-preference items, interspersed target and nontarget trials, an observing response, and the presentation of the vocalizations in "motherese" speech. Results showed substantial increases in target vocalizations above baseline levels and above nontarget vocalizations for two of three participants. PMID- 27274974 TI - Cultural and Linguistic Diversity in Recent Verbal Behavior Research on Individuals with Disabilities: a Review and Implications for Research and Practice. AB - The number of individuals from various culture and language backgrounds who are receiving behavior-analytic services is growing. Therefore, a behavioral understanding of the role of cultural and linguistic diversity (CLD) in language acquisition may be warranted. We searched recent editions of The Analysis of Verbal Behavior and the Journal of Applied Behavior Analysis to determine the degree to which researchers report the CLD of individuals with disabilities who participate in verbal behavior research. Our results indicate that researchers in these journals rarely report the culture and language background of their participants. Given these results, we provide a conceptual analysis and describe implications for research and clinical practice. A further understanding of the role of CLD may aid in the development of better behavioral interventions and culturally sensitive treatments. Finally, research that explores the role of CLD in language acquisition may add to the generality of behavior-analytic research and practice. PMID- 27274975 TI - Caregivers as Interventionists and Trainers: Teaching Mands to Children with Developmental Disabilities. AB - We evaluated the use of behavioral skills training (BST) to train caregivers to conduct procedures commonly associated with mand training. We trained two caregivers on the following procedures: (a) conducting preference assessments, (b) delivering preferred items contingent on appropriate behavior, (c) capturing and contriving motivating operations, (d) conducting probes to assess the child's current mand repertoire, (e) errorless prompting procedures using echoic prompts, (f) vocal shaping, (g) collecting data, and (h) correcting errors. We also assessed whether a trained caregiver could in turn train their spouse on these procedures. We evaluated the effects of the intervention on the frequency of child spontaneous and prompted mands. The three caregivers performed near zero percent accuracy during baseline but increased to above 80 % accuracy with training, and high performance persisted during most maintenance probes. These results were replicated for the parent who received training from their spouse. In addition, spontaneous mands were occurring more frequently than prompted mands by the end of the study. The implications of caregivers implementing mand training procedures based on Skinner's analysis of verbal behavior are discussed. PMID- 27274976 TI - An Investigation of Stimulus Pairing and Listener Training to Establish Emergent Intraverbals in Children with Autism. AB - We examined two methods to facilitate the emergence of untaught intraverbal responses to children with autism. Listener behavior training (LT) involved reinforcement of a selection-based response following presentation of an array of pictures on an iPad(r) and an auditory instruction describing a characteristic of the picture. Stimulus pairing (SP) involved presentation of one picture in isolation on the iPad(r) and an auditory instruction describing a characteristic of the picture. Participants were not required to emit an overt vocal response during SP. Results indicate both procedures were effective at producing some untaught intraverbal responses, but a transfer of stimulus control procedure was required for two of the three participants to meet mastery criterion. Results are discussed in terms of necessary prerequisite skills for each procedure, and the requirement of an overt or echoic response to help facilitate the emergence of intraverbals. PMID- 27274977 TI - Selection-Based Instruction and the Emergence of Topography-Based Responses to Interview Questions. PMID- 27274978 TI - Emerging Tacts and Selections from Previous Learned Skills: A Comparison between Two Types of Naming. AB - Naming consists of tacting an object and selecting it upon hearing its name as a result of emergence. After acquiring naming, children learn object-name relations more quickly and, hence, it is an important achievement in development. We studied the acquisition of the two skills that define naming, using two procedures, in seven typically developing 4-year-old children. The tact-selection procedure consisted of (a) teaching tacts of objects (or pictures) and probing for object selection upon hearing the objects' names, and (b) teaching object selection and probing tacts. The pairing procedure consisted of presenting objects (or pictures) at the same time that an adult said their names, without requiring from the child other response than attending. Of the seven children, five showed emergence of selection responses and tacts. Children showed more instances of emergence with the tact-selection procedure than with the pairing procedure and with three-dimensional (3-D) objects than with pictures. The results have important implications for teaching preschool children and children with learning disabilities. PMID- 27274979 TI - Simple and Conditional Discrimination and Specific Reinforcement in Teaching Reading: An Intervention Package. AB - This study evaluated an intervention package combining simple and conditional discrimination training and specific reinforcement for each stimulus class in teaching reading of simple words to individuals with intellectual disabilities. In conditional discrimination training, participants matched printed words and pictures to the recorded sounds made by the pictured objects and animals. Fourteen children and adolescents with intellectual disabilities were assigned to an experimental and a control group. The two groups' performance did not differ in the pretest. The experimental group demonstrated equivalence class formation and read the words that participated in the equivalence classes, whereas the control group did not. PMID- 27274980 TI - Clinical epidemiology of vancomycin-resistant Enterococcus gallinarum and Enterococcus casseliflavus bloodstream infections. AB - This study aimed to evaluate the clinical outcomes of vancomycin-resistant enterococcal bloodstream infections (VRE BSI) caused by Enterococcus gallinarum or Enterococcus casseliflavus. Variables associated with treatment failure were determined and treatment options were compared. This was a national retrospective study of hospitalised Veterans Affairs patients with non-faecium, non-faecalis VRE BSI. The primary outcome was treatment failure, defined as a composite of: (i) 30-day all-cause mortality; (ii) microbiological failure; and (iii) 30-day VRE BSI recurrence. Stepwise Poisson regression was conducted to determine variables associated with treatment failure. In total, 48 patients were included, with 29 cases (60.4%) caused by E. gallinarum and 19 cases (39.6%) caused by E. casseliflavus. Among these cases, 20 (41.7%) were treated with an anti-VRE agent (linezolid or daptomycin) and 28 (58.3%) were treated with an anti-enterococcal beta-lactam. Overall, 30-day mortality was 10.4% (5/48) and composite treatment failure was 39.6% (19/48). In multivariate analysis, treatment with an anti enterococcal beta-lactam was associated with increased treatment failure in comparison with anti-VRE therapy (adjusted risk ratio = 1.73, 95% confidence interval 1.06-4.97; P = 0.031). Overall, treatment with linezolid or daptomycin for vancomycin-resistant E. gallinarum or E. casseliflavus BSI resulted in improved clinical outcomes in comparison with anti-enterococcal beta-lactam treatment. PMID- 27274981 TI - Assessing Uncertainties of Theoretical Atomic Transition Probabilities with Monte Carlo Random Trials. AB - This paper suggests a method of evaluation of uncertainties in calculated transition probabilities by randomly varying parameters of an atomic code and comparing the results. A control code has been written to randomly vary the input parameters with a normal statistical distribution around initial values with a certain standard deviation. For this particular implementation, Cowan's suite of atomic codes (R.D. Cowan, The Theory of Atomic Structure and Spectra, Berkeley, CA: University of California Press, 1981) was used to calculate radiative rates of magnetic-dipole and electric-quadrupole transitions within the ground configuration of titanium-like iron, Fe V. The Slater parameters used in the calculations were adjusted to fit experimental energy levels with Cowan's least squares fitting program, RCE. The standard deviations of the fitted parameters were used as input of the control code providing the distribution widths of random trials for these parameters. Propagation of errors through the matrix diagonalization and summation of basis state expansions leads to significant variations in the resulting transition rates. These variations vastly differ in their magnitude for different transitions, depending on their sensitivity to errors in parameters. With this method, the rate uncertainty can be individually assessed for each calculated transition. PMID- 27274982 TI - Exploring the motivations behind misreporting self-measured blood glucose in adolescents with type 1 diabetes - a qualitative study. AB - BACKGROUND: Despite advances in diabetes management, the reporting and self monitoring of blood glucose (SMBG) remains fundamental. While previous work has established that the misreporting of SMBG to family and medical professionals is surprisingly common, the motivations behind this behaviour have never been examined. We aimed to investigate the motivations behind misreporting of SMBG in adolescents with type 1 diabetes (T1DM). METHODS: Fifteen semi-structured interviews were conducted with adolescents (aged 12-19 inclusive) with T1DM recruited through diabetes clinics across the Otago/Southland region of New Zealand from November 2015 to January 2016. These were transcribed and content analysis performed to identify themes and subthemes in misreporting behaviour. RESULTS: The mean age of participants was 15.7 years, 60 % were male, with 67 % using multiple daily insulin injections, and 33 % on insulin pumps. Their median HbA1c was 84 mmol/mol, range 52-130. Misreporting behaviour was described for both electronic pump records and written logbooks, as well as verbally. Multiple motivations for misreporting were given, spanning three major themes: Achieving potential benefits; the avoidance of negative consequences; and the avoidance of worry/concern (in self or in others). The main suggestion of participants to reduce misreporting behaviour was to reduce the negative reactions of others to suboptimal blood glucose readings. CONCLUSION: Electronic, written, and verbal SMBG misreporting remains common. This study provides deeper insight into the motivations leading to this behaviour in adolescents, suggesting that further understanding and attention to this aspect of adherence may lead to improvements not only in glycaemic control and safety, but also to the psychological wellbeing of those with T1DM. PMID- 27274983 TI - Immunologic special forces: anti-pathogen cytotoxic T-lymphocyte immunotherapy following hematopoietic stem cell transplantation. AB - Anti-pathogen adoptive T-cell immunotherapy has been proven to be highly effective in preventing or controlling viral infections following hematopoietic stem cell transplantation. Recent advances in manufacturing protocols allow an increased number of targeted pathogens, eliminate the need for viral transduction, broaden the potential donor pool to include pathogen-naive sources, and reduce the time requirement for production. Early studies suggest that anti fungal immunotherapy may also have clinical benefit. Future advances include further broadening of the pathogens that can be targeted and development of T cells with resistance to pharmacologic immunosuppression. PMID- 27274984 TI - A Quantitative Genomic Approach for Analysis of Fitness and Stress Related Traits in a Drosophila melanogaster Model Population. AB - The ability of natural populations to withstand environmental stresses relies partly on their adaptive ability. In this study, we used a subset of the Drosophila Genetic Reference Panel, a population of inbred, genome-sequenced lines derived from a natural population of Drosophila melanogaster, to investigate whether this population harbors genetic variation for a set of stress resistance and life history traits. Using a genomic approach, we found substantial genetic variation for metabolic rate, heat stress resistance, expression of a major heat shock protein, and egg-to-adult viability investigated at a benign and a higher stressful temperature. This suggests that these traits will be able to evolve. In addition, we outline an approach to conduct pathway associations based on genomic linear models, which has potential to identify adaptive genes and pathways, and therefore can be a valuable tool in conservation genomics. PMID- 27274986 TI - Bioinformatics Applications in Life Sciences and Technologies. PMID- 27274985 TI - Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens. AB - The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are multidrug resistant isolates, which is one of the greatest challenges in clinical practice. Multidrug resistance is amongst the top three threats to global public health and is usually caused by excessive drug usage or prescription, inappropriate use of antimicrobials, and substandard pharmaceuticals. Understanding the resistance mechanisms of these bacteria is crucial for the development of novel antimicrobial agents or other alternative tools to combat these public health challenges. Greater mechanistic understanding would also aid in the prediction of underlying or even unknown mechanisms of resistance, which could be applied to other emerging multidrug resistant pathogens. In this review, we summarize the known antimicrobial resistance mechanisms of ESKAPE pathogens. PMID- 27274987 TI - Association between the Type of Workplace and Lung Function in Copper Miners. AB - The aim of the analysis was to retrospectively assess changes in lung function in copper miners depending on the type of workplace. In the groups of 225 operators, 188 welders, and 475 representatives of other jobs, spirometry was performed at the start of employment and subsequently after 10, 20, and 25 years of work. Spirometry Longitudinal Data Analysis software was used to estimate changes in group means for FEV1 and FVC. Multiple linear regression analysis was used to assess an association between workplace and lung function. Lung function assessed on the basis of calculation of longitudinal FEV1 (FVC) decline was similar in all studied groups. However, multiple linear regression model used in cross-sectional analysis revealed an association between workplace and lung function. In the group of welders, FEF75 was lower in comparison to operators and other miners as early as after 10 years of work. Simultaneously, in smoking welders, the FEV1/FVC ratio was lower than in nonsmokers (p < 0,05). The interactions between type of workplace and smoking (p < 0,05) in their effect on FVC, FEV1, PEF, and FEF50 were shown. Among underground working copper miners, the group of smoking welders is especially threatened by impairment of lung ventilatory function. PMID- 27274988 TI - Diagnostic Value of White Blood Cell and C-Reactive Protein in Pediatric Appendicitis. AB - Background. Acute appendicitis (AA) associated with acute phase reaction is the most prevalent disease which requires emergency surgery. Its delayed diagnosis and unnecessarily performed appendectomies lead to numerous complications. In our study, we aimed to detect the role of WBC and CRP in the exclusion of acute and complicated appendicitis and diagnostic accuracy in pediatric age group. Methods. Appendectomized patient groups were constructed based on the results of histological evaluation. The area under a receiver operating characteristic (ROC) curve (AUC) was performed to examine diagnostic accuracy. Results. When WBC and CRP were used in combination, based on cut-off values of >=13.1 * 10(3)/MUL for WBC counts and >=1.17 mg/dL for CRP level, diagnostic parameters were as follows: sensitivity, 98.7%; specificity, 71.3%; PPV, 50.6%; NPV, 99.5%; diagnostic accuracy, 77.6%; LR(+), 3.44; LR(-), 0.017. AUC values were 0.845 (95% CI 0.800 0.891) for WBC and 0.887 (95% CI 0.841-0.932) for CRP. Conclusions. For complicated appendicitis, CRP has the highest degree of diagnostic accuracy. The diagnosis of appendicitis should be made primarily based on clinical examination, and obviously more specific and systemic inflammatory markers are needed. Combined use of cut-off values of WBC (>=13100/MUL) and CRP (>=1.17 mg/L) yields a higher sensitivity and NPV for the diagnosis of complicated appendicitis. PMID- 27274989 TI - Combinatorial Antitumor Effect of Rapamycin and beta-Elemene in Follicular Thyroid Cancer Cells. AB - Background. mTOR signaling would be a promising target for thyroid cancer therapy. However, in clinical trials, objective response rate with mTOR inhibitor monotherapy in most cancer types was modest. A new focus on development of combinatorial strategies with rapalogs is increasing. Objective. Investigating the combinatorial antitumor effect of rapamycin and beta-elemene in follicular thyroid cancer cells. Methods. MTT assay was used to determine the FTC-133 cell proliferation after culturing with rapamycin and/or beta-elemene. To analyze their combinatorial effect, immunoblotting was performed to analyze the activation status of AKT. Moreover, beta-elemene attenuated rapamycin-induced immunosuppression was tested in mice. Results. Combination of rapamycin and beta elemene exerted significant synergistic antiproliferative effects in FTC-133 cell lines in vitro, based on inhibiting the AKT feedback activation induced by rapamycin. In vivo, the beta-elemene could attenuate rapamycin-induced immunosuppression via reversing imbalance of Treg/Th17, with the underlying mechanism needed to be declared. Conclusions. We demonstrate that the novel combination of mTOR inhibitor with beta-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation. PMID- 27274990 TI - Tanshinone IIA Alleviates the AD Phenotypes in APP and PS1 Transgenic Mice. AB - Therapeutic approach for Alzheimer's disease (AD) is still deficient. To find active compounds from herbal medicine is of interest in the alleviation of AD symptoms. This study aimed to investigate the protective effects of Tanshinone IIA (TIIA) on memory performance and synaptic plasticity in a transgenic AD model at the early phase. 25-100 mg/kg TIIA (intraperitoneal injection, i.p.) was administered to the six-month-old APP and PS1 transgenic mice for 30 consecutive days. After treatment, spatial memory, synaptic plasticity, and related mechanisms were investigated. Our result showed that memory impairment in AD mice was mitigated by 50 and 100 mg/kg TIIA treatments. Hippocampal long-term potentiation was impaired in AD model but rescued by 100 mg/kg TIIA treatment. Mechanically, TIIA treatment reduced the accumulations of beta-amyloid 1-42, C terminal fragments (CTFs), and p-Tau in the AD model. TIIA did not affect basal BDNF but promoted depolarization-induced BDNF synthesis in the AD mice. Taken together, TIIA repairs hippocampal LTP and memory, likely, through facilitating the clearance of AD-related proteins and activating synaptic BDNF synthesis. TIIA might be a candidate drug for AD treatment. PMID- 27274991 TI - Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study. AB - Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H(+)-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction. PMID- 27274992 TI - Toxoplasma gondii and Neospora caninum in Free-Range Chickens in Henan Province of China. AB - Background. Chickens serve as an intermediate host for Toxoplasma gondii and Neospora caninum; infection of free-range (FR) chickens with these organisms is a useful indicator of soil and environmental contamination with oocysts. A total of 700 FR chicken serum samples and 300 heart samples were collected from Henan province from March to July 2015. Antibodies to T. gondii were found in 18.86% (132/700) of the chickens by modified agglutination test (cut-off 1 : 25), while 23.14% (162/700) were positive for N. caninum by indirect fluorescent antibody test (cut-off 1 : 25). T. gondii DNA was detected in the myocardium digestion liquids of 4/25 (16%) FR chickens. The PCR results of N. caninum DNA from FR chicken myocardium digestion liquids (n = 25) were all negative. Attempts to isolate viable T. gondii were unsuccessful. The results showed that there were antibodies to T. gondii and N. caninum in FR chickens from Henan province. Accordingly, effective control of feces from cats and dogs and improved pets hygiene habits were needed. To the author's knowledge, this is the first report of the presence of N. caninum antibody in chickens from China. PMID- 27274993 TI - Three-Dimensional Computer-Aided Detection of Microcalcification Clusters in Digital Breast Tomosynthesis. AB - We propose computer-aided detection (CADe) algorithm for microcalcification (MC) clusters in reconstructed digital breast tomosynthesis (DBT) images. The algorithm consists of prescreening, MC detection, clustering, and false-positive (FP) reduction steps. The DBT images containing the MC-like objects were enhanced by a multiscale Hessian-based three-dimensional (3D) objectness response function and a connected-component segmentation method was applied to extract the cluster seed objects as potential clustering centers of MCs. Secondly, a signal-to-noise ratio (SNR) enhanced image was also generated to detect the individual MC candidates and prescreen the MC-like objects. Each cluster seed candidate was prescreened by counting neighboring individual MC candidates nearby the cluster seed object according to several microcalcification clustering criteria. As a second step, we introduced bounding boxes for the accepted seed candidate, clustered all the overlapping cubes, and examined. After the FP reduction step, the average number of FPs per case was estimated to be 2.47 per DBT volume with a sensitivity of 83.3%. PMID- 27274994 TI - Synergistic Effects of Six Chronic Disease Pairs on Decreased Physical Activity: The SMILE Cohort Study. AB - Little is known about whether and how two chronic diseases interact with each other in modifying the risk of physical inactivity. The aim of the present study is to identify chronic disease pairs that are associated with compliance or noncompliance with the Dutch PA guideline recommendation and to study whether specific chronic disease pairs indicate an extra effect on top of the effects of the diseases individually. Cross-sectional data from 3,386 participants of cohort study SMILE were used and logistic regression analysis was performed to study the joint effect of the two diseases of each chronic disease pair for compliance with the Dutch PA guideline. For six chronic disease pairs, patients suffering from both diseases belonging to these disease pairs in question show a higher probability of noncompliance to the Dutch PA guideline, compared to what one would expect based on the effects of each of the two diseases alone. These six chronic disease pairs were chronic respiratory disease and severe back problems; migraine and inflammatory joint disease; chronic respiratory disease and severe kidney disease; chronic respiratory disease and inflammatory joint disease; inflammatory joint disease and rheumatoid arthritis; and rheumatoid arthritis and osteoarthritis of the knees, hips, and hands. PMID- 27274995 TI - Evaluation of Qualitative Changes in Simulated Periodontal Ligament and Alveolar Bone Using a Noncontact Electromagnetic Vibration Device with a Laser Displacement Sensor. AB - Evaluating periodontal tissue condition is an important diagnostic parameter in periodontal disease. Noncontact electromagnetic vibration device (NEVD) was previously developed to monitor this condition using mechanical parameters. However, this system requires accelerometer on the target tooth. This study assessed application of laser displacement sensor (LDS) to NEVD without accelerometer using experimental tooth models. Tooth models consisted of cylindrical rod, a tissue conditioner, and polyurethane or polyurethane foam to simulate tooth, periodontal ligament, and alveolar bone, respectively. Tissue conditioner was prepared by mixing various volumes of liquid with powder. Mechanical parameters (resonant frequency, elastic modulus, and coefficient of viscosity) were assessed using NEVD with the following methods: Group A, measurement with accelerometer; Group B, measurement with LDS in the presence of accelerometer; and Group C, measurement with LDS in the absence of accelerometer. Mechanical parameters significantly decreased with increasing liquid volume. Significant differences were also observed between the polyurethane and polyurethane foam models. Meanwhile, no statistically significant differences were observed between Groups A and B; however, most mechanical parameters in Group C were significantly larger and more distinguishable than those of Groups A and B. LDS could measure mechanical parameters more accurately and clearly distinguished the different periodontal ligament and alveolar bone conditions. PMID- 27274996 TI - The Relationships between Anabolic Hormones and Body Composition in Middle-Aged and Elderly Men with Prediabetes: A Cross-Sectional Study. AB - The influence of anabolic hormones and body composition in men with prediabetes (PD) is unknown. In a cross-sectional study we investigated the relationships between total testosterone (TT), calculated free testosterone (cFT), dehydroepiandrosterone sulfate (DHEAS), and insulin-like growth factor 1 (IGF-1) and body composition assessed using dual-energy X-ray absorptiometry (DXA) method in 84 patients with PD (40-80 years) and 56 men in control group. Patients with PD had lower TT, cFT, and DHEAS levels but similar IGF-1 levels in both groups. Patients with PD presented the higher total and abdominal fat as well as the lower total and abdominal lean than control (p < 0.02, p < 0.01, p < 0.05, and p < 0.02, resp.). We observed negative relationship between TT and total fat (p = 0.014) and positive with abdominal lean mass (p = 0.034), while cFT was negatively associated with abdominal (p = 0.02), trunk (p = 0.024), and leg fat (p = 0.037) and positively associated with total (p = 0.022) and trunk lean (p = 0.024). DHEAS were negatively associated with total fat (p = 0.045), and IGF-1 were positively associated with abdominal (p = 0.003) and leg lean (p = 0.015). In conclusion, the lowered anabolic hormones are involved in body composition rearrangement in men with PD. Further studies are needed to establish whether the androgen replacement therapy would be beneficial in men with PD. PMID- 27274997 TI - A Molecular and Whole Body Insight of the Mechanisms Surrounding Glucose Disposal and Insulin Resistance with Hypoxic Treatment in Skeletal Muscle. AB - Although the mechanisms are largely unidentified, the chronic or intermittent hypoxic patterns occurring with respiratory diseases, such as chronic pulmonary disease or obstructive sleep apnea (OSA) and obesity, are commonly associated with glucose intolerance. Indeed, hypoxia has been widely implicated in the development of insulin resistance either via the direct action on insulin receptor substrate (IRS) and protein kinase B (PKB/Akt) or indirectly through adipose tissue expansion and systemic inflammation. Yet hypoxia is also known to encourage glucose transport using insulin-dependent mechanisms, largely reliant on the metabolic master switch, 5' AMP-activated protein kinase (AMPK). In addition, hypoxic exposure has been shown to improve glucose control in type 2 diabetics. The literature surrounding hypoxia-induced changes to glycemic control appears to be confusing and conflicting. How is it that the same stress can seemingly cause insulin resistance while increasing glucose uptake? There is little doubt that acute hypoxia increases glucose metabolism in skeletal muscle and does so using the same pathway as muscle contraction. The purpose of this review paper is to provide an insight into the mechanisms underpinning the observed effects and to open up discussions around the conflicting data surrounding hypoxia and glucose control. PMID- 27274999 TI - Randomized Phase II Study of Docetaxel plus Personalized Peptide Vaccination versus Docetaxel plus Placebo for Patients with Previously Treated Advanced Wild Type EGFR Non-Small-Cell Lung Cancer. AB - Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m(2) on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed. PMID- 27275000 TI - Comparison of Indiana High School Football Injury Rates by Inclusion of the USA Football "Heads Up Football" Player Safety Coach. AB - BACKGROUND: In Indiana, high school football coaches are required to complete a coaching education course with material related to concussion awareness, equipment fitting, heat emergency preparedness, and proper technique. Some high schools have also opted to implement a player safety coach (PSC). The PSC, an integral component of USA Football's Heads Up Football (HUF) program, is a coach whose primary responsibility is to ensure that other coaches are implementing proper tackling and blocking techniques alongside other components of the HUF program. PURPOSE: To compare injury rates in Indiana high school football teams by their usage of a PSC or online coaching education only. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Athletic trainers (ATs) evaluated and tracked injuries at each practice and game during the 2015 high school football season. Players were drawn from 6 teams in Indiana. The PSC group, which used the PSC component, was comprised of 204 players from 3 teams. The "education only" group (EDU), which utilized coaching education only, was composed of 186 players from 3 teams. Injury rates and injury rate ratios (IRRs) were reported with 95% confidence intervals (CIs). RESULTS: During 25,938 athlete-exposures (AEs), a total of 149 injuries were reported, of which 54 (36.2%) and 95 (63.8%) originated from the PSC and EDU groups, respectively. The practice injury rate was lower in the PSC group than the EDU group (2.99 vs 4.83/1000 AEs; IRR, 0.62; 95% CI, 0.40-0.95). The game injury rate was also lower in the PSC group than the EDU group (11.37 vs 26.37/1000 AEs; IRR, 0.43; 95% CI, 0.25-0.74). When restricted to concussions only, the rate was lower in the PSC group (0.09 vs 0.73/1000 AEs; IRR, 0.12; 95% CI, 0.01-0.94), although only 1 concussion was reported in the PSC group. No differences were found in game concussion rates (0.60 vs 4.39/1000 AEs; IRR, 0.14; 95% CI, 0.02-1.11). CONCLUSION: Findings support the PSC as an effective method of injury mitigation in high school football. Future research should seek to replicate this study using larger samples from additional states. PMID- 27275001 TI - Recombinant Human Elastase Treatment of Cephalic Veins. AB - BACKGROUND: Vessel injury at the time of Arteriovenous Fistula (AVF) creation may lead to neointimal hyperplasia that impairs AVF maturation. Vonapanitase, a recombinant human chymotrypsin-like elastase family member 1, is an investigational drug under development to improve AVF maturation and patency. The current studies were designed to document vonapanitase effects in human cephalic veins that are used in AVF creation. METHODS: Human cephalic veins were mounted on a perfusion myograph. Vonapanitase 1.2, 4, 13.2, and 40 MUg/ml or saline was applied drop wise on the vein followed by saline rinse. Vein segments were cut into rings for elastin content determination by desmosine radioimmunoassay and histology. Fluorescently-labelled vonapanitase was applied to veins and adventitial imaging was performed using laser scanning confocal microscopy. In vivo time course experiments were performed by treating rabbit jugular veins and harvesting 1 h and 4 h after vonapanitase treatment. RESULTS / CONCLUSION: Vonapanitase reduced desmosine content in a dose-related manner. Histology also confirmed a dose-related reduction in elastic fiber staining. Fluorescently labelled vonapanitase persistently localized to elastic fibers in the vein adventitia. In vivo experiments showed a reduction in desmosine content in jugular veins from 1 h to 4 h following treatment. These data suggest that vonapanitase targets elastin in elastic fibers in a dose related manner and that elastase remains in the vessel wall and has catalytic activity for at least 1 h. PMID- 27274998 TI - Adjuvants: Classification, Modus Operandi, and Licensing. AB - Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations. PMID- 27275002 TI - Major vault protein in cardiac and smooth muscle. AB - Major vault protein (MVP) is the major component of the vault particle whose functions are not well understood. One proposed function of the vault is to serve as a mechanism of drug transport, which confers drug resistance in cancer cells. We show that MVP can be found in cardiac and smooth muscle. In human airway smooth muscle cells, knocking down MVP was found to cause cell death, suggesting that MVP serves as a cell survival factor. Further, our laboratory found that MVP is S-glutathionylated in response to ligand/receptor-mediated cell signaling. The S-glutathionylation of MVP appears to regulate protein-protein interactions between MVP and a protein called myosin heavy chain 9 (MYH9). Through MYH9 and Vsp34, MVP may form a complex with Beclin-1 that regulates autophagic cell death. In pulmonary vascular smooth muscle, proteasome inhibition promotes the ubiquitination of MVP, which may function as a mechanism of proteasome inhibition mediated cell death. Investigating the functions and the regulatory mechanisms of MVP and vault particles is an exciting new area of research in cardiovascular/pulmonary pathophysiology. PMID- 27275003 TI - Western Analysis of Histone Modifications (Aspergillus nidulans). AB - Western blotting allows for the specific detection of proteins and/or modifications of proteins by an antibody of interest. This protocol utilizes a crude nuclei extraction protocol for Aspergillus nidulans to enrich for histones and other nuclear proteins prior to gel electrophoresis. Post translational modifications of histones may then be easily detected. After electrophoresis, the selected antibodies are used to detect and quantify levels of the modifications of interest. PMID- 27275005 TI - Genetic Analysis of Reduced gamma-Tocopherol Content in Ethiopian Mustard Seeds. AB - Ethiopian mustard (Brassica carinata A. Braun) line BCT-6, with reduced gamma tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced gamma-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both gamma- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of gamma-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of gamma-tocopherol is required. PMID- 27275006 TI - Visuomotor Map Determines How Visually Guided Reaching Movements are Corrected Within and Across Trials. AB - When a visually guided reaching movement is unexpectedly perturbed, it is implicitly corrected in two ways: immediately after the perturbation by feedback control (online correction) and in the next movement by adjusting feedforward motor commands (offline correction or motor adaptation). Although recent studies have revealed a close relationship between feedback and feedforward controls, the nature of this relationship is not yet fully understood. Here, we show that both implicit online and offline movement corrections utilize the same visuomotor map for feedforward movement control that transforms the spatial location of visual objects into appropriate motor commands. First, we artificially distorted the visuomotor map by applying opposite visual rotations to the cursor representing the hand position while human participants reached for two different targets. This procedure implicitly altered the visuomotor map so that changes in the movement direction to the target location were more insensitive or more sensitive. Then, we examined how such visuomotor map distortion influenced online movement correction by suddenly changing the target location. The magnitude of online movement correction was altered according to the shape of the visuomotor map. We also examined offline movement correction; the aftereffect induced by visual rotation in the previous trial was modulated according to the shape of the visuomotor map. These results highlighted the importance of the visuomotor map as a foundation for implicit motor control mechanisms and the intimate relationship between feedforward control, feedback control, and motor adaptation. PMID- 27275007 TI - Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Botzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition. AB - The rhythm of breathing in mammals, originating within the brainstem pre Botzinger complex (pre-BotC), is presumed to be generated by glutamatergic neurons, but this has not been directly demonstrated. Additionally, developmental expression of the transcription factor Dbx1 or expression of the neuropeptide somatostatin (Sst), has been proposed as a marker for the rhythmogenic pre-BotC glutamatergic neurons, but it is unknown whether these other two phenotypically defined neuronal populations are functionally equivalent to glutamatergic neurons with regard to rhythm generation. To address these problems, we comparatively investigated, by optogenetic approaches, the roles of pre-BotC glutamatergic, Dbx1-derived, and Sst-expressing neurons in respiratory rhythm generation in neonatal transgenic mouse medullary slices in vitro and also more intact adult perfused brainstem-spinal cord preparations in situ. We established three different triple-transgenic mouse lines with Cre-driven Archaerhodopsin-3 (Arch) expression selectively in glutamatergic, Dbx1-derived, or Sst-expressing neurons for targeted photoinhibition. In each line, we identified subpopulations of rhythmically active, Arch-expressing pre-BotC inspiratory neurons by whole-cell recordings in medullary slice preparations in vitro, and established that Arch mediated hyperpolarization of these inspiratory neurons was laser power dependent with equal efficacy. By site- and population-specific graded photoinhibition, we then demonstrated that inspiratory frequency was reduced by each population with the same neuronal voltage-dependent frequency control mechanism in each state of the respiratory network examined. We infer that enough of the rhythmogenic pre BotC glutamatergic neurons also have the Dbx1 and Sst expression phenotypes, and thus all three phenotypes share the same voltage-dependent frequency control property. PMID- 27275008 TI - Rank Order Coding: a Retinal Information Decoding Strategy Revealed by Large Scale Multielectrode Array Retinal Recordings. AB - How a population of retinal ganglion cells (RGCs) encodes the visual scene remains an open question. Going beyond individual RGC coding strategies, results in salamander suggest that the relative latencies of a RGC pair encode spatial information. Thus, a population code based on this concerted spiking could be a powerful mechanism to transmit visual information rapidly and efficiently. Here, we tested this hypothesis in mouse by recording simultaneous light-evoked responses from hundreds of RGCs, at pan-retinal level, using a new generation of large-scale, high-density multielectrode array consisting of 4096 electrodes. Interestingly, we did not find any RGCs exhibiting a clear latency tuning to the stimuli, suggesting that in mouse, individual RGC pairs may not provide sufficient information. We show that a significant amount of information is encoded synergistically in the concerted spiking of large RGC populations. Thus, the RGC population response described with relative activities, or ranks, provides more relevant information than classical independent spike count- or latency- based codes. In particular, we report for the first time that when considering the relative activities across the whole population, the wave of first stimulus-evoked spikes is an accurate indicator of stimulus content. We show that this coding strategy coexists with classical neural codes, and that it is more efficient and faster. Overall, these novel observations suggest that already at the level of the retina, concerted spiking provides a reliable and fast strategy to rapidly transmit new visual scenes. PMID- 27275004 TI - Translational aspects in targeting the stromal tumour microenvironment: from bench to bedside. AB - Solid tumours comprise, not only malignant cells but also a variety of stromal cells and extracellular matrix proteins. These components interact via an array of signalling pathways to create an adaptable network that may act to promote or suppress cancer progression. To date, the majority of anti-tumour chemotherapeutic agents have principally sought to target the cancer cell. Consequently, resistance develops because of clonal evolution, as a result of selection pressure during tumour expansion. The concept of activating or inhibiting other cell types within the tumour microenvironment is relatively novel and has the advantage of targeting cells which are genetically stable and less likely to develop resistance. This review outlines key players in the stromal tumour microenvironment and discusses potential targeting strategies that may offer therapeutic benefit. PMID- 27275009 TI - Liver Injury Assessment by Vetscan VS2 Analyzer and Most Frequently Used ALT/GTP Reagent. AB - BACKGROUND AND AIM: Liver injury is estimated by serum alanine aminotransferases (ALT) levels in experimental animal models. Laboratories use various techniques to measure ALT levels including assay reagents and chemistry analyzers. VetScan VS2 (VS2) is widely used in veterinary clinics and research laboratories for highly reproducible, convenient and effective testing. Alternatively, ALT liquid reagent is used by laboratories to estimate liver injury in animal studies. The aim of this study was to perform comparative analyses of data obtained from these two assays in two different animal models. METHODS: In this study, we used two different mouse models and compared the ALT levels measured using VetScan VS2 chemistry analyzer and ALT liquid reagent. Immunohistochemical analysis of hepatic tissue was also performed to document liver pathology. The first model is a high fat diet feeding model that results in a mild hepatic steatosis (fat accumulation in the liver) without elevation of ALT levels. For a severe liver injury model, we employed a hepatotoxin-induced liver injury model (carbon tetrachloride, CCl4), which leads to the development of hepatic fibrosis and very high ALT levels. RESULTS: VetScan VS2 and ALT reagent gave different values of ALT for all animal groups. However, linear regression analysis showed a significantly high association between ALT levels obtained by VS2 and ALT liquid reagent in a high-fat feeding model with no liver injury. For the CCl4 induced liver injury model, serum dilution (5 and 10 times) was performed to obtain accurate results with ALT reagent. ALT levels acquired from both techniques showed a close association. Interestingly, this correlation was closer when serum was diluted 5 fold. CONCLUSION: This study demonstrates that both methods give similar results when evaluating liver injury in animal studies. However, the serum dilution factor is critical for severe liver injury assessment when using ALT reagent and requires some optimization. In this regard, VetScan VS2 is easier to use and gives comparable results. PMID- 27275010 TI - High-Throughput Luciferase-Based Assay for the Discovery of Therapeutics That Prevent Malaria. AB - In order to identify the most attractive starting points for drugs that can be used to prevent malaria, a diverse chemical space comprising tens of thousands to millions of small molecules may need to be examined. Achieving this throughput necessitates the development of efficient ultra-high-throughput screening methods. Here, we report the development and evaluation of a luciferase-based phenotypic screen of malaria exoerythrocytic-stage parasites optimized for a 1536 well format. This assay uses the exoerythrocytic stage of the rodent malaria parasite, Plasmodium berghei, and a human hepatoma cell line. We use this assay to evaluate several biased and unbiased compound libraries, including two small sets of molecules (400 and 89 compounds, respectively) with known activity against malaria erythrocytic-stage parasites and a set of 9886 diversity-oriented synthesis (DOS)-derived compounds. Of the compounds screened, we obtain hit rates of 12-13 and 0.6% in preselected and naive libraries, respectively, and identify 52 compounds with exoerythrocytic-stage activity less than 1 MUM and having minimal host cell toxicity. Our data demonstrate the ability of this method to identify compounds known to have causal prophylactic activity in both human and animal models of malaria, as well as novel compounds, including some exclusively active against parasite exoerythrocytic stages. PMID- 27275011 TI - Next-generation profiling to identify the molecular etiology of Parkinson dementia. AB - OBJECTIVE: We sought to determine the underlying cortical gene expression changes associated with Parkinson dementia using a next-generation RNA sequencing approach. METHODS: In this study, we used RNA sequencing to evaluate differential gene expression and alternative splicing in the posterior cingulate cortex from neurologically normal control patients, patients with Parkinson disease, and patients with Parkinson disease with dementia. RESULTS: Genes overexpressed in both disease states were involved with an immune response, whereas shared underexpressed genes functioned in signal transduction or as components of the cytoskeleton. Alternative splicing analysis produced a pattern of immune and RNA processing disturbances. CONCLUSIONS: Genes with the greatest degree of differential expression did not overlap with genes exhibiting significant alternative splicing activity. Such variation indicates the importance of broadening expression studies to include exon-level changes because there can be significant differential splicing activity with potential structural consequences, a subtlety that is not detected when examining differential gene expression alone, or is underrepresented with probe-limited array technology. PMID- 27275012 TI - Mutation of TBCK causes a rare recessive developmental disorder. AB - OBJECTIVE: To characterize the underlying genetic defect in a family with 3 siblings affected by a severe, yet viable, congenital disorder. METHODS: Extensive genetic and metabolic investigations were performed, and the affected children were imaged at different ages. Whole-genome genotyping and whole-exome sequencing were undertaken. A single large region (>8 Mb) of homozygosity in chromosome 4 (chr4:100,268,553-108,609,628) was identified that was shared only in affected siblings. Inspection of genetic variability within this region led to the identification of a novel mutation. Sanger sequencing confirmed segregation of the mutation with disease. RESULTS: All affected siblings share homozygosity for a novel 4-bp deletion in the gene TBCK (NM_033115:c.614_617del:p.205_206del). CONCLUSIONS: This finding provides the genetic cause of a severe inherited disease in a family and extends the number of mutations and phenotypes associated with this recently identified disease gene. PMID- 27275013 TI - Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis. AB - In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a "wave" of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 * 104 to 9.9 * 107 MUm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3 of lung tissue to a maximum of 11.1 per mm3 of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair. PMID- 27275014 TI - Deficiency of mitochondrial modulator MCJ promotes chemoresistance in breast cancer. AB - Despite major advances in early detection and prognosis, chemotherapy resistance is a major hurdle in the battle against breast cancer. Identifying predictive markers and understanding the mechanisms are key steps to overcoming chemoresistance. Methylation-controlled J protein (MCJ, also known as DNAJC15) is a negative regulator of mitochondrial respiration and has been associated with chemotherapeutic drug sensitivity in cancer cell lines. Here we show, in a retrospective study of a large cohort of breast cancer patients, that low MCJ expression in breast tumors predicts high risk of relapse in patients treated with chemotherapy; however, MCJ expression does not correlate with response to endocrine therapy. In a prospective study in breast cancer patients undergoing neoadjuvant therapy, low MCJ expression also correlates with poor clinical response to chemotherapy and decreased disease-free survival. Using MCJ-deficient mice, we demonstrate that lack of MCJ is sufficient to induce mammary tumor chemoresistance in vivo. Thus, loss of expression of this endogenous mitochondrial modulator in breast cancer promotes the development of chemoresistance. PMID- 27275015 TI - Abnormal PTPN11 enhancer methylation promotes rheumatoid arthritis fibroblast like synoviocyte aggressiveness and joint inflammation. AB - The PTPN11 gene, encoding the tyrosine phosphatase SHP-2, is overexpressed in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) compared with osteoarthritis (OA) FLS and promotes RA FLS invasiveness. Here, we explored the molecular basis for PTPN11 overexpression in RA FLS and the role of SHP-2 in RA pathogenesis. Using computational methods, we identified a putative enhancer in PTPN11 intron 1, which contained a glucocorticoid receptor- binding (GR-binding) motif. This region displayed enhancer function in RA FLS and contained 2 hypermethylation sites in RA compared with OA FLS. RA FLS stimulation with the glucocorticoid dexamethasone induced GR binding to the enhancer and PTPN11 expression. Glucocorticoid responsiveness of PTPN11 was significantly higher in RA FLS than OA FLS and required the differentially methylated CpGs for full enhancer function. SHP-2 expression was enriched in the RA synovial lining, and heterozygous Ptpn11 deletion in radioresistant or innate immune cells attenuated K/BxN serum transfer arthritis in mice. Treatment with SHP-2 inhibitor 11a-1 reduced RA FLS migration and responsiveness to TNF and IL-1beta stimulation and reduced arthritis severity in mice. Our findings demonstrate how abnormal epigenetic regulation of a pathogenic gene determines FLS behavior and demonstrate that targeting SHP-2 or the SHP-2 pathway could be a therapeutic strategy for RA. PMID- 27275016 TI - Glycoprofiling of cancer biomarkers: Label-free electrochemical lectin-based biosensors. AB - Glycosylation of biomolecules is one of the most prevalent post- and co translational modification in a human body, with more than half of all human proteins being glycosylated. Malignant transformation of cells influences glycosylation machinery resulting in subtle changes of the glycosylation pattern within the cell populations as a result of cancer. Thus, an altered terminal glycan motif on glycoproteins could provide a warning signal about disease development and progression and could be applied as a reliable biomarker in cancer diagnostics. Among all highly effective glycoprofiling tools, label-free electrochemical impedance spectroscopy (EIS)-based biosensors have emerged as especially suitable tool for point-of-care early-stage cancer detection. Herein, we highlight the current challenges in glycoprofiling of various cancer biomarkers by ultrasensitive impedimetric-based biosensors with low sample consumption, low cost fabrication and simple miniaturization. Additionally, this review provides a short introduction to the field of glycomics and lectinomics and gives a brief overview of glycan alterations in different types of cancer. PMID- 27275018 TI - Information Propagation in Prior-Image-Based Reconstruction. AB - Advanced reconstruction methods for computed tomography include sophisticated forward models of the imaging system that capture the pertinent physical processes affecting the signal and noise in projection measurements. However, most do little to integrate prior knowledge of the subject - often relying only on very general notions of local smoothness or edges. In many cases, as in longitudinal surveillance or interventional imaging, a patient has undergone a sequence of studies prior to the current image acquisition that hold a wealth of prior information on patient-specific anatomy. While traditional techniques tend to treat each data acquisition as an isolated event and disregard such valuable patient-specific prior information, some reconstruction methods, such as PICCS[1] and PIR-PLE[2], can incorporate prior images into a reconstruction objective function. Inclusion of such information allows for dramatic reduction in the data fidelity requirements and more robustly accommodate substantial undersampling and exposure reduction with consequent benefits to imaging speed and reduced radiation dose. While such prior-image-based methods offer tremendous promise, the introduction of prior information in the reconstruction raises significant concern regarding the accurate representation of features in the image and whether those features arise from the current data acquisition or from the prior images. In this work we propose a novel framework to analyze the propagation of information in prior-image-based reconstruction by decomposing the estimation into distinct components supported by the current data acquisition and by the prior image. This decomposition quantifies the contributions from prior and current data as a spatial map and can trace specific features in the image to their source. Such "information source maps" can potentially be used as a check on confidence that a given image feature arises from the current data or from the prior and to more quantitatively guide the selection of parameter values affecting the strength of prior information in the resulting image. PMID- 27275017 TI - Sphingosine 1-Phosphate Receptor 2 Regulates the Migration, Proliferation, and Differentiation of Mesenchymal Stem Cells. AB - Mesenchymal stem cells (MSCs) are a multipotent cell population acquired most prominently from bone marrow with the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, and others. MSCs demonstrate the capacity to home to sites of injury and contribute to tissue repair. Sphingosine 1-phosphate (S1P) is a biologically active sphingolipid impacting proliferation, apoptosis, inflammation, and angiogenesis with changes in S1P concentration providing significant implications for various disease conditions including cancer, diabetes, and cardiac disease. These functions are primarily mediated by interactions with 5 G-protein coupled S1P receptors (S1PR1-5). In this paper, we demonstrate that inhibition of S1PR2 results in increased MSC clonogenicity, migration, and proliferation; features dependent on Erk phosphorylation. Furthermore, decreased S1PR2 expression decreases the differentiation of MSCs into adipocytes and mature osteoblasts that may be the result of increased expression of MSC pluripotency factors including Nanog, Sox-9, and Oct-4. Inhibition of S1PR1 and S1PR3 in contrast does not impact MSC migration or Erk activation although increased proliferation is observed. In the study, we describe the essential role of S1PR2 in MSC differentiation pathways through modification of pluripotency factors. We propose a MAPK dependent mechanism through S1PR2 inhibition that promotes equally multipotent MSC proliferation. PMID- 27275019 TI - Heuristics in Managing Complex Clinical Decision Tasks in Experts' Decision Making. AB - BACKGROUND: Clinical decision support is a tool to help experts make optimal and efficient decisions. However, little is known about the high level of abstractions in the thinking process for the experts. OBJECTIVE: The objective of the study is to understand how clinicians manage complexity while dealing with complex clinical decision tasks. METHOD: After approval from the Institutional Review Board (IRB), three clinical experts were interviewed the transcripts from these interviews were analyzed. RESULTS: We found five broad categories of strategies by experts for managing complex clinical decision tasks: decision conflict, mental projection, decision trade-offs, managing uncertainty and generating rule of thumb. CONCLUSION: Complexity is created by decision conflicts, mental projection, limited options and treatment uncertainty. Experts cope with complexity in a variety of ways, including using efficient and fast decision strategies to simplify complex decision tasks, mentally simulating outcomes and focusing on only the most relevant information. APPLICATION: Understanding complex decision making processes can help design allocation based on the complexity of task for clinical decision support design. PMID- 27275020 TI - Supporting novice clinicians cognitive strategies: System design perspective. AB - Infections occur among all clinical domains. The changing nature of microbes, viruses and infections poses a great threat to the overall well-being in medicine. Clinicians in the infectious disease (ID) domain deal with diagnostic as well as treatment uncertainty in their everyday practice. Our current health information technology (HIT) systems do not consider the level of clinician expertise into the system design process. Thus, information is presented to both novice and expert ID clinicians in identical ways. The purpose of this study was to identify the cognitive strategies novice ID clinicians use in managing complex cases to make better recommendations for system design. In the process, we interviewed 14 ID experts and asked them to give us a detailed description of how novice clinicians would have dealt with complex cases. From the interview transcripts, we identified four major themes that expert clinicians suggested about novices' cognitive strategies including: A) dealing with uncertainty, B) lack of higher macrocognition, C) oversimplification of problems through heuristics and D) dealing with peer pressure. Current and future innovative decision support tools embedded in the electronic health record that can match these cognitive strategies may hold the key to cognitively supporting novice clinicians. The results of this study may open up avenues for future research and suggest design directions for better healthcare systems. PMID- 27275021 TI - Context matters: A community-based study of urban minority parents' views on child health. AB - BACKGROUND: Among children, there are substantial ethno-racial minority disparities across a broad range of health-related behaviors, experiences, and outcomes. Addressing these disparities is important, as childhood and adolescence establish health trajectories that extend throughout life. METHODS: The current study employed a community-based participatory research approach to gain community insight on child health priorities and to frame an intervention aimed at improving the health of minority children. Eight focus groups were conducted among seventy-five African American parents in a Southeastern city. The current study was guided by an ecological theoretical framework. RESULTS: Although the focus of this investigation was on community identification of child health priorities, participants cited, as root determinants, contextual factors, which included lack of healthy food options, lack of spaces for physical activity, and community violence. These co-occurring factors were related to limited engagement in outdoor activities and physical activity, increased obesity, and poor mental health and coping. Poor parenting was cited as the most substantial barrier to improving child health outcomes, and quality parenting was identified as the most important issue to address for community programs focused on promoting the health and success of children. For improving health outcomes for children in their neighborhoods, establishment of positive social capital and constructive activities were also cited. CONCLUSIONS: These results reinforce social determinants of health as influences on child health outcomes and describe how community engagement can address potential solutions through interventions that resonate with program participants. PMID- 27275022 TI - Cross-domain, soft-partition clustering with diversity measure and knowledge reference. AB - Conventional, soft-partition clustering approaches, such as fuzzy c-means (FCM), maximum entropy clustering (MEC) and fuzzy clustering by quadratic regularization (FC-QR), are usually incompetent in those situations where the data are quite insufficient or much polluted by underlying noise or outliers. In order to address this challenge, the quadratic weights and Gini-Simpson diversity based fuzzy clustering model (QWGSD-FC), is first proposed as a basis of our work. Based on QWGSD-FC and inspired by transfer learning, two types of cross-domain, soft-partition clustering frameworks and their corresponding algorithms, referred to as type-I/type-II knowledge-transfer-oriented c-means (TI-KT-CM and TII-KT CM), are subsequently presented, respectively. The primary contributions of our work are four-fold: (1) The delicate QWGSD-FC model inherits the most merits of FCM, MEC and FC-QR. With the weight factors in the form of quadratic memberships, similar to FCM, it can more effectively calculate the total intra-cluster deviation than the linear form recruited in MEC and FC-QR. Meanwhile, via Gini Simpson diversity index, like Shannon entropy in MEC, and equivalent to the quadratic regularization in FC-QR, QWGSD-FC is prone to achieving the unbiased probability assignments, (2) owing to the reference knowledge from the source domain, both TI-KT-CM and TII-KT-CM demonstrate high clustering effectiveness as well as strong parameter robustness in the target domain, (3) TI-KT-CM refers merely to the historical cluster centroids, whereas TII-KT-CM simultaneously uses the historical cluster centroids and their associated fuzzy memberships as the reference. This indicates that TII-KT-CM features more comprehensive knowledge learning capability than TI-KT-CM and TII-KT-CM consequently exhibits more perfect cross-domain clustering performance and (4) neither the historical cluster centroids nor the historical cluster centroid based fuzzy memberships involved in TI-KT-CM or TII-KT-CM can be inversely mapped into the raw data. This means that both TI-KT-CM and TII-KT-CM can work without disclosing the original data in the source domain, i.e. they are of good privacy protection for the source domain. In addition, the convergence analyses regarding both TI-KT-CM and TII-KT-CM are conducted in our research. The experimental studies thoroughly evaluated and demonstrated our contributions on both synthetic and real-life data scenarios. PMID- 27275023 TI - Plankton dynamics and biogeochemical fluxes in the Costa Rica Dome: introduction to the CRD Flux and Zinc Experiments. AB - The Costa Rica Dome (CRD) is an open-ocean upwelling system in the Eastern Tropical Pacific that overlies the ocean's largest oxygen minimum zone (OMZ). The region has unique characteristics, biomass dominance by picophytoplankton, suppressed diatoms, high biomass of higher consumers and presumptive trace metal limitation, but is poorly understood in terms of pelagic stock and process relationships, including productivity and production controls. Here, we describe the goals, project design, physical context and major findings of the Flux and Zinc Experiments cruise conducted in June-July 2010 to assess trophic flux relationships and elemental controls on phytoplankton in the CRD. Despite sampling during a year of suppressed summertime surface chlorophyll, cruise results show high productivity (~1 g C m-2 day-1), high new production relative to export, balanced production and grazing, disproportionate biomass-specific productivity of large phytoplankton and high zooplankton stocks. Zinc concentrations are low in surface waters relative to phosphorous and silicate in other regions, providing conditions conducive to picophytoplankton, like Synechococcus, with low Zn requirements. Experiments nonetheless highlight phytoplankton limitation or co-limitation by silicic acid, driven by a strong silica pump that is linked to low dissolution of biogenic silica in the cold shallow thermocline of the lower euphotic zone. PMID- 27275024 TI - Patterns of microbial community biomass, composition and HPLC diagnostic pigments in the Costa Rica upwelling dome. AB - We investigated biomass, size-structure, composition, depth distributions and spatial variability of the phytoplankton community in the Costa Rica Dome (CRD) in June-July 2010. Euphotic zone profiles were sampled daily during Lagrangian experiments in and out of the dome region, and the community was analyzed using a combination of digital epifluorescence microscopy, flow cytometry and HPLC pigments. The mean depth-integrated biomass of phytoplankton ranged 2-fold, from 1089 to 1858 mg C m-2 (mean +/- SE = 1378 +/- 112 mg C m-2), among 4 water parcels tracked for 4 days. Corresponding mean (+/-SE) integrated values for total chlorophyll a (Chl a) and the ratio of autotrophic carbon to Chl a were 24.1 +/- 1.5 mg Chl a m-2 and 57.5 +/- 3.4, respectively. Absolute and relative contributions of picophytoplankton (~60%), Synechococcus (>33%) and Prochlorococcus (17%) to phytoplankton community biomass were highest in the central dome region, while >20 um phytoplankton accounted for <=10%, and diatoms <2%, of biomass in all areas. Nonetheless, autotrophic flagellates, dominated by dinoflagellates, exceeded biomass contributions of Synechococcus at all locations. Order-of-magnitude discrepancies in the relative contributions of diatoms (overestimated) and dinoflagellates (underestimated) based on diagnostic pigments relative to microscopy highlight potential significant biases associated with making community inferences from pigments. PMID- 27275025 TI - Phytoplankton production and taxon-specific growth rates in the Costa Rica Dome. AB - During summer 2010, we investigated phytoplankton production and growth rates at 19 stations in the eastern tropical Pacific, where winds and strong opposing currents generate the Costa Rica Dome (CRD), an open-ocean upwelling feature. Primary production (14C-incorporation) and group-specific growth and net growth rates (two-treatment seawater dilution method) were estimated from samples incubated in situ at eight depths. Our cruise coincided with a mild El Nino event, and only weak upwelling was observed in the CRD. Nevertheless, the highest phytoplankton abundances were found near the dome center. However, mixed-layer growth rates were lowest in the dome center (~0.5-0.9 day-1), but higher on the edge of the dome (~0.9-1.0 day-1) and in adjacent coastal waters (0.9-1.3 day-1). We found good agreement between independent methods to estimate growth rates. Mixed-layer growth rates of Prochlorococcus and Synechococcus were largely balanced by mortality, whereas eukaryotic phytoplankton showed positive net growth (~0.5-0.6 day-1), that is, growth available to support larger (mesozooplankton) consumer biomass. These are the first group-specific phytoplankton rate estimates in this region, and they demonstrate that integrated primary production is high, exceeding 1 g C m-2 day-1 on average, even during a period of reduced upwelling. PMID- 27275026 TI - Net biogenic silica production and the contribution of diatoms to new production and organic matter export in the Costa Rica Dome ecosystem. AB - We determined the net rate of biogenic silica (bSiO2) production and estimated the diatom contribution to new production and organic matter export in the Costa Rica Dome during summer 2010. The shallow thermocline significantly reduces bSiO2 dissolution rates below the mixed layer, leading to significant enhancement of bSiO2 relative to organic matter (silicate-pump condition). This may explain why deep export of bSiO2 in this region is elevated by an order of magnitude relative to comparable systems. Diatom carbon, relative to autotrophic carbon, was low (<3%); however, the contribution of diatoms to new production averaged 3 and 13% using independent approaches. The 4-old discrepancy between methods may be explained by a low average C:Si ratio (~1.4) for the net produced diatom C relative to the net produced bSiO2. We speculate that this low production ratio is not the result of reduced C, but may arise from a significant contribution of non-diatom silicifying organisms to bSiO2 production. The contribution of diatoms to organic matter export was minor (5.7%). These results, and those of the broader project, suggest substantial food-web transformation of diatom organic matter in the euphotic zone, which creates enriched bSiO2 relative to organic matter within the exported material. PMID- 27275027 TI - Biomass and composition of protistan grazers and heterotrophic bacteria in the Costa Rica Dome during summer 2010. AB - We investigated biomass and composition of heterotrophic microbes in the Costa Rica Dome during June-July 2010 as part of a broader study of plankton trophic dynamics. Because picophytoplankton (<2 MUm) are known to dominate in this unique upwelling region, we hypothesized tight biomass relationships between size determined predator-prey pairs (i.e. picoplankton-nano-grazers, nanoplankton micro-grazers) within the microbial community. Integrated biomass of heterotrophic bacteria ranged from 180 to 487 mg C m-2 and was significantly correlated with total autotrophic carbon. Heterotrophic protist (H-protist) biomass ranged more narrowly from 488 to 545 mg C m-2, and was comprised of 60% dinoflagellates, 30% other flagellates and 11% ciliates. Nano-sized (<20 MUm) protists accounted for the majority (57%) of grazer biomass and were positively correlated with picoplankton, partially supporting our hypothesis, but nanoplankton and micro-grazers (>20 MUm) were not significantly correlated. The relative constancy of H-protist biomass among locations despite clear changes in integrated autotrophic biomass, Chl a, and primary production suggests that mesozooplankton may exert a tight top-down control on micro-grazers. Biomass specific consumption rates of phytoplankton by protistan grazers suggest an instantaneous growth rate of 0.52 day-1 for H-protists, similar to the growth rate of phytoplankton and consistent with a trophically balanced ecosystem dominated by pico-nanoplankton interactions. PMID- 27275028 TI - Preferential depletion of zinc within Costa Rica upwelling dome creates conditions for zinc co-limitation of primary production. AB - The Costa Rica Dome (CRD) is a wind-driven feature characterized by high primary production and an unusual cyanobacterial bloom in surface waters. It is not clear whether this bloom arises from top-down or bottom-up processes. Several studies have argued that trace metal geochemistry within the CRD contributes to the composition of the phytoplankton assemblages, since cyanobacteria and eukaryotic phytoplankton have different transition metal requirements. Here, we report that total dissolved zinc (Zn) is significantly depleted relative to phosphate (P) and silicate (Si) within the upper water column of the CRD compared with other oceanic systems, and this may create conditions favorable for cyanobacteria, which have lower Zn requirements than their eukaryotic competitors. Shipboard grow-out experiments revealed that while Si was a limiting factor under our experimental conditions, additions of Si and either iron (Fe) or Zn led to higher biomass than Si additions alone. The addition of Fe and Zn alone did not lead to significant enhancements. Our results suggest that the depletion of Zn relative to P in upwelled waters may create conditions in the near-surface waters that favor phytoplankton with low Zn requirements, including cyanobacteria. PMID- 27275029 TI - Microplankton trace element contents: implications for mineral limitation of mesozooplankton in an HNLC area. AB - Mesozooplankton production in high-nutrient low-chlorophyll regions of the ocean may be reduced if the trace element concentrations in their food are insufficient to meet growth and metabolic demands. We used elemental microanalysis (SXRF) of single-celled plankton to determine their trace metal contents during a series of semi-Lagrangian drift studies in an HNLC upwelling region, the Costa Rica Dome (CRD). Cells from the surface mixed layer had lower Fe:S but higher Zn:S and Ni:S than those from the subsurface chlorophyll maximum at 22-30 m. Diatom Fe:S values were typically 3-fold higher than those in flagellated cells. The ratios of Zn:C in flagellates and diatoms were generally similar to each other, and to co occurring mesozooplankton. Estimated Fe:C ratios in flagellates were lower than those in co-occurring mesozooplankton, sometimes by more than 3-fold. In contrast, Fe:C in diatoms was typically similar to that in zooplankton. RNA:DNA ratios in the CRD were low compared with other regions, and were related to total autotrophic biomass and weakly to the discrepancy between Zn:C in flagellated cells and mesozooplankton tissues. Mesozooplankton may have been affected by the trace element content of their food, even though trace metal limitation of phytoplankton was modest at best. PMID- 27275030 TI - Phytoplankton growth and microzooplankton grazing dynamics across vertical environmental gradients determined by transplant in situ dilution experiments. AB - The Costa Rica Dome (CRD) represents a classic case of the bloom-forming capacity of small phytoplankton. Unlike other upwelling systems, autotrophic biomass in the CRD is dominated by picocyanobacteria and small eukaryotes that outcompete larger diatoms and reach extremely high biomass levels. We investigated responses of the subsurface phytoplankton community of the CRD to changes associated with vertical displacement of water masses, coupling in situ transplanted dilution experiments with flow cytometry and epifluorescence microscopy to assess group specific dynamics. Growth rates of Synechococcus (SYN) and photosynthetic picoeukaryotes (PEUK) were positively correlated with light (Rpearson_SYN = 0.602 and Rpearson_PEUK = 0.588, P < 0.001). Growth rates of Prochlorococcus (PRO), likely affected by photoinhibition, were not light correlated (Rpearson_PRO = 0.101, P = 0.601). Overall, grazing and growth rates were closely coupled in all picophytoplankton groups (Rspearman_PRO = 0.572, Rspearman_SYN = 0.588, Rspearman_PEUK = 0.624), and net growth rates remained close to zero. Conversely, the abundance and biomass of larger phytoplankton, mainly diatoms, increased more than 10-fold in shallower transplant incubations indicating that, in addition to trace-metal chemistry, light also plays a significant role in controlling microphytoplankton populations in the CRD. PMID- 27275031 TI - Biological response of Costa Rica Dome phytoplankton to Light, Silicic acid and Trace metals. AB - The Costa Rica Dome (CRD) is a unique open-ocean upwelling system, with picophytoplankton dominance of phytoplankton biomass and suppressed diatoms, yet paradoxically high export of biogenic silica. As a part of Flux and Zinc Experiments cruise in summer (June-July 2010), we conducted shipboard incubation experiments in the CRD to examine the potential roles of Si, Zn, Fe and light as regulating factors of phytoplankton biomass and community structure. Estimates of photosynthetic quantum yields revealed an extremely stressed phytoplankton population that responded positively to additions of silicic acid, iron and zinc and higher light conditions. Size-fractioned Chl a yielded the surprising result that picophytoplankton, as well as larger phytoplankton, responded most to treatments with added silicic acid incubated at high incident light (HL + Si). The combination of Si and HL also led to increases in cell sizes of picoplankton, notably in Synechococcus. Such a response, coupled with the recent discovery of significant intracellular accumulation of Si in some picophytoplankton, suggests that small phytoplankton could play a potentially important role in Si cycling in the CRD, which may help to explain its peculiar export characteristics. PMID- 27275032 TI - Vertical distribution of Eucalanoid copepods within the Costa Rica Dome area of the Eastern Tropical Pacific. AB - A variety of ecological strategies for tolerance of low-oxygen conditions within the Costa Rica Dome (CRD) area of the Eastern Tropical Pacific are documented for the copepod family Eucalanidae. During the summer of 2010, we compared the ecological strategies used by the Eucalanidae inside and outside the central CRD region. We compared the vertical and horizontal distributions of five species, Eucalanus inermis, Subeucalanus subtenuis, Subeucalanus subcrassus, Subeucalanus pileatus and Pareucalanus attenuatus together with Rhincalanus species, in the epipelagic (upper 200 m) among four locations, which we grouped into a section roughly crossing the core CRD area (inside-outside core CRD). The coastal area outside the CRD supported the most diverse assemblage, whereas overall abundance of Eucalanidae in the central CRD was 2-fold greater than outside and dominated by E. inermis (>60%). Eucalanidae in the central CRD had a shallow depth distribution, closely associated with the shallow thermocline (10-20 m). There was no evidence of daily vertical migration in the central CRD, but E. inermis demonstrated vertical migration outside the CRD. The vertical abundance patterns of Eucalanidae in the CRD region reflect complex interactions between subtle physical-chemical differences and food resources. PMID- 27275033 TI - Mesozooplankton biomass and grazing in the Costa Rica Dome: amplifying variability through the plankton food web. AB - We investigated standing stocks and grazing rates of mesozooplankton assemblages in the Costa Rica Dome (CRD), an open-ocean upwelling ecosystem in the eastern tropical Pacific. While phytoplankton biomass in the CRD is dominated by picophytoplankton (<2-um cells) with especially high concentrations of Synechococcus spp., we found high mesozooplankton biomass (~5 g dry weight m-2) and grazing impact (12-50% integrated water column chlorophyll a), indicative of efficient food web transfer from primary producers to higher levels. In contrast to the relative uniformity in water-column chlorophyll a and mesozooplankton biomass, variability in herbivory was substantial, with lower rates in the central dome region and higher rates in areas offset from the dome center. While grazing rates were unrelated to total phytoplankton, correlations with cyanobacteria (negative) and biogenic SiO2 production (positive) suggest that partitioning of primary production among phytoplankton sizes contributes to the variability observed in mesozooplankton metrics. We propose that advection of upwelled waters away from the dome center is accompanied by changes in mesozooplankton composition and grazing rates, reflecting small changes within the primary producers. Small changes within the phytoplankton community resulting in large changes in the mesozooplankton suggest that the variability in lower trophic level dynamics was effectively amplified through the food web. PMID- 27275034 TI - Factors affecting Fe and Zn contents of mesozooplankton from the Costa Rica Dome. AB - Mineral limitation of mesozooplankton production is possible in waters with low trace metal availability. As a step toward estimating mesozooplankton Fe and Zn requirements under such conditions, we measured tissue concentrations of major and trace nutrient elements within size-fractioned zooplankton samples collected in and around the Costa Rica Upwelling Dome, a region where phytoplankton growth may be co-limited by Zn and Fe. The geometric mean C, N, P contents were 27, 5.6 and 0.21 mmol gdw-1, respectively. The values for Fe and Zn were 1230 and 498 nmol gdw-1, respectively, which are low compared with previous measurements. Migrant zooplankton caused C and P contents of the 2-5 mm fraction to increase at night relative to the day while the Fe and Zn contents decreased. Fe content increased with size while Zn content decreased with size. Fe content was strongly correlated to concentrations of two lithogenic tracers, Al and Ti. We estimate minimum Fe:C ratios in large migrant and resident mixed layer zooplankton to be 15 and 60 umol mol-1, respectively. The ratio of Zn:C ranged from 11 umol mol-1 for the 0.2-0.5 mm size fraction to 33 umol mol-1 for the 2-5 mm size fraction. PMID- 27275035 TI - The biological pump in the Costa Rica Dome: an open-ocean upwelling system with high new production and low export. AB - The Costa Rica Dome is a picophytoplankton-dominated, open-ocean upwelling system in the Eastern Tropical Pacific that overlies the ocean's largest oxygen minimum zone. To investigate the efficiency of the biological pump in this unique area, we used shallow (90-150 m) drifting sediment traps and 234Th:238U deficiency measurements to determine export fluxes of carbon, nitrogen and phosphorus in sinking particles. Simultaneous measurements of nitrate uptake and shallow water nitrification allowed us to assess the equilibrium balance of new and export production over a monthly timescale. While f-ratios (new:total production) were reasonably high (0.36 +/- 0.12, mean +/- standard deviation), export efficiencies were considerably lower. Sediment traps suggested e-ratios (export/14C-primary production) at 90-100 m ranging from 0.053 to 0.067. ThE-ratios (234Th disequilibrium-derived export) ranged from 0.038 to 0.088. C:N and N:P stoichiometries of sinking material were both greater than canonical (Redfield) ratios or measured C:N of suspended particulates, and they increased with depth, suggesting that both nitrogen and phosphorus were preferentially remineralized from sinking particles. Our results are consistent with an ecosystem in which mesozooplankton play a major role in energy transfer to higher trophic levels but are relatively inefficient in mediating vertical carbon flux to depth, leading to an imbalance between new production and sinking flux. PMID- 27275036 TI - Phytoplankton production and grazing balances in the Costa Rica Dome. AB - We investigated phytoplankton production rates and grazing fates in the Costa Rica Dome (CRD) during summer 2010 based on dilution depth profiles analyzed by flow cytometry and pigments and mesozooplankton grazing assessed by gut fluorescence. Three community production estimates, from 14C uptake (1025 +/- 113 mg C m-2 day-1) and from dilution experiments analyzed for total Chla (990 +/- 106 mg C m-2 day-1) and flow cytometry populations (862 +/- 71 mg C m-2 day-1), exceeded regional ship-based values by 2-3-fold. Picophytoplankton accounted for 56% of community biomass and 39% of production. Production profiles extended deeper for Prochlorococcus (PRO) and picoeukaryotes than for Synechococcus (SYN) and larger eukaryotes, but 93% of total production occurred above 40 m. Microzooplankton consumed all PRO and SYN growth and two-third of total production. Positive net growth of larger eukaryotes in the upper 40 m was balanced by independently measured consumption by mesozooplankton. Among larger eukaryotes, diatoms contributed ~3% to production. On the basis of this analysis, the CRD region is characterized by high production and grazing turnover, comparable with or higher than estimates for the eastern equatorial Pacific. The region nonetheless displays characteristics atypical of high productivity, such as picophytoplankton dominance and suppressed diatom roles. PMID- 27275038 TI - Maximizing organ yield from deceased Lead donors. PMID- 27275037 TI - Diazotroph community structure in the deep oxygen minimum zone of the Costa Rica Dome. AB - Oxygen minimum zones (OMZs), characterized by depleted dissolved oxygen concentration in the intermediate depth of the water column, are predicted to expand under the influence of global warming. Recent studies in the Eastern Tropical South Pacific Ocean and Arabian Sea have reported that heterotrophic nitrogen fixation is active in the OMZs. In this study, we investigated the community structure of diazotrophs in the OMZ of the Costa Rica Dome (CRD) upwelling region in the Eastern Tropical North Pacific Ocean, using 454 pyrosequencing of nifH gene amplicons. Comparing diazotroph assemblages in different depth strata of the OMZ (200-1000 m in depth), we found a unique diazotroph community in the OMZ core, which was mainly dominated by methanotroph like diazotrophs, suggesting a potential coupling of nitrogen cycle and methane assimilation. In addition, some OTUs revealed in this study, especially those belonging to the large sub-cluster Vibrio diazotrophicus, were reported to be abundant and expressing the nifH gene in other OMZs. Our results suggest that the unique hydrographic conditions in OMZs may support similar assemblages of diazotrophs, and heterotrophic nitrogen fixation could also be occurring in our studied region. Our study provides the first insight into the composition and distribution of putative diazotrophs in the CRD OMZ. PMID- 27275039 TI - Dexmedetomidine: The game changer or a team player? PMID- 27275040 TI - Brain death and care of the organ donor. AB - Brain death has specific implications for organ donation with the potential for saving several lives. Awareness on maintenance of the brain dead has increased over the last decade with the progress in the field of transplant. The diagnosis of brain death is clinical and can be confirmed by apnea testing. Ancillary tests can be considered when the apnea test cannot be completed or is inconclusive. Reflexes of spinal origin may be present and should not be confused against the diagnosis of brain death. Adequate care for the donor targeting hemodynamic indices and lung protective ventilator strategies can improve graft quality for donation. Hormone supplementation using thyroxine, antidiuretic hormone, corticosteroid and insulin has shown to improve outcomes following transplant. India still ranks low compared to the rest of the world in deceased donation. The formation of organ sharing networks supported by state governments has shown a substantial increase in the numbers of deceased donors primarily by creating awareness and ensuring protocols in caring for the donor. This review describes the steps in the establishment of brain death and the management of the organ donor. Material for the review was collected through a Medline search, and the search terms included were brain death and organ donation. PMID- 27275041 TI - Amniotic fluid embolism. AB - Amniotic fluid embolism (AFE) is one of the catastrophic complications of pregnancy in which amniotic fluid, fetal cells, hair, or other debris enters into the maternal pulmonary circulation, causing cardiovascular collapse. Etiology largely remains unknown, but may occur in healthy women during labour, during cesarean section, after abnormal vaginal delivery, or during the second trimester of pregnancy. It may also occur up to 48 hours post-delivery. It can also occur during abortion, after abdominal trauma, and during amnio-infusion. The pathophysiology of AFE is not completely understood. Possible historical cause is that any breach of the barrier between maternal blood and amniotic fluid forces the entry of amniotic fluid into the systemic circulation and results in a physical obstruction of the pulmonary circulation. The presenting signs and symptoms of AFE involve many organ systems. Clinical signs and symptoms are acute dyspnea, cough, hypotension, cyanosis, fetal bradycardia, encephalopathy, acute pulmonary hypertension, coagulopathy etc. Besides basic investigations lung scan, serum tryptase levels, serum levels of C3 and C4 complements, zinc coproporphyrin, serum sialyl Tn etc are helpful in establishing the diagnosis. Treatment is mainly supportive, but exchange transfusion, extracorporeal membrane oxygenation, and uterine artery embolization have been tried from time to time. The maternal prognosis after amniotic fluid embolism is very poor though infant survival rate is around 70%. PMID- 27275042 TI - Intravenous sub-anesthetic ketamine for perioperative analgesia. AB - Ketamine, an N-methyl-d-aspartate antagonist, blunts central pain sensitization at sub-anesthetic doses (0.3 mg/kg or less) and has been studied extensively as an adjunct for perioperative analgesia. At sub-anesthetic doses, ketamine has a minimal physiologic impact though it is associated with a low incidence of mild psychomimetic symptoms as well as nystagmus and double vision. Contraindications to its use do exist and due to ketamine's metabolism, caution should be exercised in patients with renal or hepatic dysfunction. Sub-anesthetic ketamine improves pain scores and reduces perioperative opioid consumption in a broad range of surgical procedures. In addition, there is evidence that ketamine may be useful in patients with opioid tolerance and for preventing chronic postsurgical pain. PMID- 27275043 TI - Effect of magnesium sulfate nebulization on the incidence of postoperative sore throat. AB - BACKGROUND AND AIMS: Postoperative sore throat (POST) is a well-recognized complication after general anesthesia (GA). Numerous nonpharmacological and pharmacological measures have been used for attenuating POST with variable success. The present study was conducted to compare the efficiency of preoperative nebulization of normal saline and magnesium sulfate in reducing the incidence of POST following GA. MATERIALS AND METHODS: Following institutional ethical committee approval and written informed consent, a prospective randomized double-blinded study was conducted in 100 cases divided into two equal groups. Patients included in the study were of either gender belonging to American Society of Anesthesiologist (ASA) status 1 or 2 undergoing elective surgery of approximately 2 h or more duration requiring tracheal intubation. Patients in Group A are nebulized with 3 ml of normal saline and the patients in Group B are nebulized with 3 ml of 225 mg isotonic nebulized magnesium sulfate for 15 min, 5 min before induction of anesthesia. The incidence of POST at rest and on swallowing and any undue complaints at 0, 2, 4, and 24 h in the postoperative period are evaluated. RESULTS: There is no significant difference in POST at rest during 0(th), 2(nd) and 4(th) h between normal saline and MgSO4. Significant difference is seen at 24(th) h, where MgSO4 lessens POST. There is no significant difference in POST on swallowing during 0(th) and 2(nd) h between normal saline and MgSO4. Significant difference is seen at 4(th) h, where MgSO4 has been shown to lessen POST. CONCLUSIONS: MgSO4 significantly reduces the incidence of POST compared to normal saline. PMID- 27275044 TI - Perioperative problems in patients with brainstem tumors and their influence on patient outcome. AB - BACKGROUND AND AIMS: Patients with brainstem tumors have many associated systemic abnormalities and are prone to develop perioperative complications. We studied the problems associated with brainstem tumors and their influence on the postoperative neurological outcome. MATERIAL AND METHODS: Retrospective review of records of patients who underwent surgery for brainstem tumors over a period of 8 years was done. Preoperative variables, perioperative complications and neurological outcome as assessed by Glasgow Outcome Scale at the time of hospital discharge were noted. Association between perioperative factors and the unfavorable neurological outcome was evaluated. RESULTS: Data of 70 patients were retrieved, 7 patients were excluded from the study because of incomplete data and data analysis was carried out for 63 patients. We found that lower cranial nerve palsies (32%) and hydrocephalus (43%) were common preoperatively. Various intraoperative problems encountered were hemodynamic instability (56%), major blood loss requiring blood transfusion (40%) and venous air embolism (11%), and postoperative problems were meningitis (51%), hypokalemia (38%), chest infection (21%), seizure (11%), deterioration of Glasgow Coma Scale (GCS, 11%), hyponatremia (8%), hydrocephalus (6%), respiratory distress (3%) and operatives site hematoma (3%). Fifty-six (89%) patients had favorable outcome at hospital discharge whereas, 7 (11%) had an unfavorable outcome. There was no association between pre- and intra-operative factors and the neurological outcome. Deterioration of GCS, chest infection, and the need for reintubation and tracheostomy were associated with unfavorable neurological outcome. CONCLUSION: Patients of brainstem tumors are at increased risk of perioperative complications. Some of the postoperative complications were associated with unfavorable neurological outcome. PMID- 27275045 TI - Incidence of hemidiaphragmatic paresis after peripheral nerve stimulator versus ultrasound guided interscalene brachial plexus block. AB - BACKGROUND AND AIMS: We compared interscalene brachial plexus block (ISBPB) using peripheral nerve stimulation (PNS) and ultrasound (US) techniques. The primary outcomes were the incidence of hemidiaphragmatic paresis (HDP) and the duration of the block. Secondary outcomes were the block success rate, time to conduct the block, onset of sensory block, and dermatomal spread, postoperative pain by Numeric Rating Scale (NRS), duration of postoperative analgesia and incidence of complications. MATERIAL AND METHODS: We conducted a prospective, randomized, and observer-blinded study in 60 patients undergoing shoulder arthroscopy under block plus general anesthesia. ISBPB was performed with 10 ml of 0.5% bupivacaine using either PNS (Group PNS, n = 30) or US (Group US, n = 30). Hemidiaphragmatic function, the primary outcome, was assessed by ultrasonographic evaluation of diaphragmatic movement and pulmonary function tests using a bedside spirometer (forced vital capacity, forced expiratory volume in 1 s and peak expiratory flow rate). General anesthesia was administered to all the patients for surgery. P < 0.05 test was considered to be statistically significant. RESULTS: Twelve patients in Group PNS had HDP and none in Group US (P < 0.0001). PFTs were also significantly reduced in Group PNS (P < 0.0001). The time to conduct the block and sensory onset time both were less in Group US (P < 0.05). The groups did not differ in block success rate, duration of analgesia, and NRS. Other complications like incidence of Horner's syndrome and vascular puncture were comparable in both the groups. CONCLUSIONS: PNS guided ISBPB with 10 ml of 0.5% bupivacaine is associated with a higher incidence of HDP as compared to US guided ISBPB. There is no significant difference in quality or duration of analgesia in the two groups. PMID- 27275046 TI - Outcomes associated with stroke volume variation versus central venous pressure guided fluid replacements during major abdominal surgery. AB - BACKGROUND AND AIMS: There is limited data on the impact of perioperative fluid therapy guided by dynamic preload variables like stroke volume variation (SVV) on outcomes after abdominal surgery. We studied the effect of SVV guided versus central venous pressure (CVP) guided perioperative fluid administration on outcomes after major abdominal surgery. MATERIAL AND METHODS: Sixty patients undergoing major abdominal surgeries were randomized into two equal groups in this prospective single blind randomized study. In the standard care group, the CVP was maintained at 10-12 mmHg while in the intervention group a SVV of 10% was achieved by the administration of fluids. The primary end-points were the length of Intensive Care Unit (ICU) and hospital stay. The secondary end points were intraoperative lactate, intravenous fluid use, requirement for inotropes, postoperative ventilation and return of bowel function. RESULTS: The ICU stay was significantly shorter in the intervention group as compared to the control group (2.9 +/- 1.15 vs. 5.4 +/- 2.71 days). The length of hospital stay was also shorter in the intervention group, (9.9 +/- 2.68 vs. 11.96 +/- 5.15 days) though not statistically significant. The use of intraoperative fluids was significantly lower in the intervention group than the control group (7721.5 +/- 4138.9 vs. 9216.33 +/- 2821.38 ml). Other secondary outcomes were comparable between the two groups. CONCLUSION: Implementation of fluid replacement guided by a dynamic preload variable (SVV) versus conventional static variables (CVP) is associated with lesser postoperative ICU stay and reduced fluid requirements in major abdominal surgery. PMID- 27275047 TI - Evaluation of low-dose dexmedetomidine and neostigmine with bupivacaine for postoperative analgesia in orthopedic surgeries: A prospective randomized double blind study. AB - BACKGROUND AND AIMS: Neuraxial adjuants to local anesthetics is an effective technique of improving the quality and duration of postoperative analgesia. The safety and efficacy of drugs like dexmedetomidine and neostigmine as epidural medications have been sparsely investigated. MATERIAL AND METHODS: Combined spinal-epidural anesthesia was performed in 60 American Society of Anesthesiologists I and II patients who required lower limb surgeries of <=3 h duration. The epidural drug was administered at the end of surgery with patients randomized into three groups. Group I, II and III received 6 ml of 0.25% bupivacaine alone, with 1 ug/kg of neostigmine and with 0.5 ug/kg of dexmedetomidine + 1 ug/kg of neostigmine, respectively. The patients were prescribed 50 mg tramadol intravenous as rescue analgesic. Patients were assessed for hemodynamic parameters, pain scores, duration of analgesia, rescue analgesic requirements and the incidence of side-effects over the next 10 h. Data was analyzed using SPSS((r)) version 17.0 (Chicago, IL, USA). P < 0.05 was considered as statistically significant. RESULTS: Patients in Group III had significantly longer mean duration of analgesia (273.5 min) compared to Group II (176.25 min) and Group I (144 min). There was increased requirement of fluids to maintain blood pressures in Group III. Neostigmine did not cause significant incidence of gastrointestinal side effects. CONCLUSIONS: Epidurally administered dexmedetomidine and neostigmine exhibit synergism in analgesic action. The incidence of drug-related side-effects was low in our study. PMID- 27275048 TI - Nitroglycerine, esmolol and dexmedetomidine for induced hypotension during functional endoscopic sinus surgery: A comparative evaluation. AB - BACKGROUND AND AIM: Induced hypotension limits intra-operative blood loss to provide better visibility of the surgical field and diminishes the incidence of major complications during functional endoscopic sinus surgery (FESS). We aimed at comparing nitroglycerine, esmolol and dexmedetomidine for inducing controlled hypotension in patients undergoing FESS. MATERIAL AND METHODS: One hundred and fifty American Society of Anesthesiologists physical status I or II adult patients undergoing FESS under general anesthesia were randomly allocated to three groups of 50 patients each. Group E received esmolol in a loading and maintenance dose of 1 mg/kg over 1 min and 0.5-1.0 mg/kg/h, respectively. Group D received a loading dose of dexmedetomidine 1 MUg/kg over 10 min followed by an infusion 0.5-1.0 MUg/kg/h, and group N received nitroglycerine infusion at a dose of 0.5-2 MUg/kg/min so as to maintain mean arterial pressure (MAP) between 60 and 70 mmHg in all the groups. The visibility of the surgical field was assessed by surgeon using Fromme and Boezaart scoring system. Hemodynamic variables, total intra-operative fentanyl consumption, emergence time and time to first analgesic request were recorded. Any side-effects were noted. The postoperative sedation was assessed using Ramsay Sedation Score. RESULT: The desired MAP (60-70 mmHg) could be achieved in all the three study groups albeit with titration of study drugs during intra-operative period. No significant intergroup difference was observed in Fromme's score during the intra-operative period. The mean total dose of fentanyl (MUg/kg) used was found to be significantly lower in group D compared to groups E and N (1.2 +/- 0.75 vs. 3.6 +/- 1.3 and 2.9 +/- 1.1 respectively). The mean heart rate was significantly lower in group D compared to groups E and N at all times of measurement (P < 0.05). The MAP was found to be significantly lower in group D compared to groups E and N after infusion of study drugs, after induction, just after intubation and 5 min after intubation (P < 0.05). The Ramsay Sedation Scores were significantly higher in group D (score 3 in 46%) when compared to group E (score 2 in 50%) and group N (score 2 in 54%) (P < 0.001). The emergence time was significantly lower in group E and group N compared to group D. Time to first analgesic request was significantly longer in group D. CONCLUSION: Dexmedetomidine and esmolol provided better hemodynamic stability and operative field visibility compared to nitroglycerin during FESS. Dexmedetomidine provides an additional benefit of reducing the analgesic requirements and providing postoperative sedation. PMID- 27275049 TI - The effects of intravenous dexmedetomidine premedication on intraocular pressure and pressor response to laryngoscopy and intubation. AB - BACKGROUND AND AIMS: Penetrating eye injuries are a challenge for the anesthesiologists in emergency due to increase in intraocular pressure (IOP). The aim of this study was to evaluate the effects of intravenous dexmedetomidine premedication on changes in IOP and hemodynamic response following laryngoscopy and tracheal intubation. MATERIAL AND METHODS: Hundred patients aged 18-60 years undergoing elective nonophthalmic surgery were divided into two groups of 50 each. Group D received a bolus dose of dexmedetomidine (0.4 MUg/kg) diluted to 20 ml normal saline and Group C received normal saline (0.4 ml/kg) over 10 min as premedication. Heart rate (HR), systolic blood pressure (SBP) and IOP were measured and recorded before premedication (T1), 5 and 10 m after premedication (T2, T3), immediately after induction, intubation and then 1, 3, 5 min after intubation (T4, 5, 6, 7, 8). RESULTS: HR was comparable in both groups at preoperative level, but it was significantly low in the drug group when compared with the control group at T4-T8 (P = 0.034, P < 0.001, 0.001, 0.036 and 0.001, respectively). The SBP was comparable in both the groups at baseline and till before induction. At T4-T8 there was a fall in SBP in Group D compared to the Group C (P = 0.045, P = 0.007, 0.001, 0.001 and 0.001, respectively). The baseline IOP was comparable in both the groups (P = NS). There was a significant fall in the IOP in Group D, 5 min after the drug infusion compared to Group C, which was sustained till 5 min after intubation (T8) (P < 0.001 at all intervals). CONCLUSION: Dexmedetomidine premedication in the dose of 0.4 MUg/kg lowers the IOP and attenuates the pressor response to laryngoscopy and intubation. PMID- 27275051 TI - Efficacy of intravenous paracetamol on pressor response in patients undergoing cesarean section under general anesthesia. AB - BACKGROUND AND AIMS: Profound hemodynamic alterations due to stress and pain during endotracheal intubation may cause deleterious effects. The purpose of this study was to evaluate the effect of intravenous (IV) paracetamol on hemodynamic changes due to endotracheal intubation during cesarean section under general anesthesia. MATERIAL AND METHODS: Random allocation of one hundred and ten patients in two groups (Group A - placebo and Group B - paracetamol), was achieved as per computer generated table. The placebo (normal saline) and paracetamol solutions looked identical as both were available in 100 ml piggy bags and were labeled as study drug. Infusion of the drug was given 1 h before surgery. Two baseline readings of heart rate, systolic blood pressure (BP), diastolic BP and mean BP were recorded before induction, and these readings were repeated during intubation. Detrimental effect on neonate was evaluated by Apgar score measured at 1 and 5 min after birth. RESULTS: There were no significant demographic differences found between the two groups. Hemodyamic changes during intubation also did not differ between the two groups. CONCLUSION: Administration of IV paracetamol 1 h before cesarean section has no significant effect in preventing hemodynamic changes at the time of endotracheal intubation. PMID- 27275050 TI - The efficacy and safety of epidural dexmedetomidine and clonidine with bupivacaine in patients undergoing lower limb orthopedic surgeries. AB - BACKGROUND AND AIMS: Alpha (alpha-2) adrenergic agonists have both analgesic and sedative properties when used as an adjuvant in regional anesthesia. A prospective randomized double-blind study was carried out to evaluate the efficacy of epidural route and to compare the efficacy and clinical profile of dexmedetomidine and clonidine as an adjuvant to bupivacaine with special emphasis on their quality of analgesia, sedation and the ability to provide the smooth intra-operative and postoperative course. MATERIAL AND METHODS: The study was conducted in prospective, randomized and double-blind manner. It included 60 American Society of Anesthesiologists Class I and II patients undergoing lower limb surgery under epidural anesthesia. Patients were randomly divided into Group A receiving 0.5% isobaric bupivacaine 15 ml with dexmedetomidine 1 MUg/kg and Group B receiving 0.5% isobaric bupivacaine 15 ml with clonidine 2 MUg/kg epidurally. Onset and duration of sensory and motor blocks, duration of analgesia, sedation, and adverse effects were assessed. RESULTS: Demographic data, surgical characteristics cardio-respiratory parameters, side-effect profile were comparable and statistically not significant in both the groups. However, sedation scores with dexmedetomidine were better than clonidine and turned out to be statistically significant. The onset times for sensory and motor blocks were significantly shorter in Group A as compared to Group B. The duration of analgesia and motor block was significantly longer in A Group as compared to Group B. CONCLUSION: Dexmedetomidine is a superior neuraxial adjuvant to bupivacaine when compared to clonidine for early onset of analgesia, superior intra-operative analgesia, stable cardio-respiratory parameters, prolonged postoperative analgesia and providing patient comfort. PMID- 27275052 TI - Dexmedetomidine versus midazolam as adjuvants to intrathecal bupivacaine: A clinical comparison. AB - BACKGROUND AND AIMS: Trials are being carried out to identify an adjuvant to intrathecal bupivacaine that preferably potentiates postoperative analgesia. This prospective, randomized, double-blind study was aimed to compare the onset and duration of sensory and motor block, postoperative analgesia and adverse effects of dexmedetomidine or midazolam given with 0.5% hyperbaric bupivacaine for spinal anesthesia. MATERIAL AND METHODS: A total of 80 patients, scheduled for vaginal hysterectomies, were randomly allocated to Group D (n = 40) to receive intrathecally 3.0 mL 0.5% hyperbaric bupivacaine +5 ug dexmedetomidine in 0.5 mL of normal saline; and Group M (n = 40) to receive 3 mL of 0.5% hyperbaric bupivacaine +2 mg midazolam in 0.4 mL (5 mg/mL) +0.1 mL normal saline. The onset, duration of sensory and motor block, time to first postoperative analgesia and side effects were noted. Power and Sample size (PS) version 3.0.0.34 was used for power and sample size calculation. Statistical analysis was performed using Microsoft (MS) Office Excel software with the Student's t-test and Chi-square test (level of significance P = 0.05). RESULTS: Duration of sensory, motor blockade and time to the first requirement of analgesia were significantly higher in Group D. Postoperative visual analog scale was significantly less in Group D than Group M. Both groups were similar with respect to sedation, hemodynamic variables and side-effects. CONCLUSION: Intrathecal dexmedetomidine was better adjuvant than midazolam as it produces significantly longer duration of sensory block, reduced doses of postoperative analgesic agents with comparable side effects. PMID- 27275053 TI - Postoperative analgesia in children: A comparison of three different doses of caudal epidural morphine. AB - BACKGROUND AND AIMS: Caudal epidural block is the most commonly used neuraxial block in children. Morphine has been used as a caudal additive for more than three decades. The aim of our study was to evaluate the efficacy and duration of analgesia of three different doses of caudal epidural morphine (CEM), and to find out the incidence of side effects. MATERIAL AND METHODS: This study was conducted on 75 patients of American Society of Anesthesiologists grades I and II, aged 2 12 years, undergoing lower abdominal and urogenital surgeries. Patients were randomly allocated to one of the three groups according to the dose of morphine. Group I received 30 MUg/kg, group II 50 MUg/kg, and group III 70 MUg/kg. Heart rate, blood pressure, oxygen saturation, electrocardiogram, pain score, sedation score, duration of analgesia, and side-effects were noted. RESULTS: The mean duration of analgesia was 8.63 h in group I, 13.36 h in group II and 19.19 h in group III. Respiratory depression was noted in three patients in group III. One patient in group I had itching. One patient each in groups I, II, and III had nausea/vomiting. CONCLUSION: CEM significantly prolongs the duration of analgesia, though with a higher dose the risk of respiratory depression should always be kept in mind. PMID- 27275054 TI - Thoracic combined spinal epidural anesthesia for laparoscopic cholecystectomy: A feasibility study. AB - BACKGROUND AND AIMS: The use of regional anesthesia for laparoscopic cholecystectomy has been reserved for patients who are at high-risk under general anesthesia (GA). The aim of this study was to assess whether thoracic combined spinal epidural (CSE) anesthesia is a feasible option for American Society of Anesthesiologists (ASA) physical status I and II patients undergoing elective laparoscopic cholecystectomy. MATERIAL AND METHODS: Thirty ASA physical status I and II patients undergoing elective laparoscopic cholecystectomy received thoracic CSE anesthesia at T9-T10 or T10-T11 interspinous space using the midline approach. Two ml of isobaric levobupivacaine 0.5% with 25 MUg of fentanyl was given intrathecally. RESULTS: Surgery was conducted successfully in all except one patient. Thoracic CSE was performed at T9-T10 interspace in 25 patients and T10-T11 interspace in five patients. Paresthesia occurred in two patients (6.6%) transiently on Whitacre needle insertion that disappeared spontaneously. Dural puncture on epidural needle insertion occurred in one patient, and intrathecal placement of epidural catheter occurred in one. Ten patients (33%) complained of shoulder pain. Conversion to GA was done in one patient due to severe shoulder pain and anxiety. Hypotension occurred in 11 patients (36%) and all responded to single dose of mephenteramine 6 mg and fluid bolus. Bradycardia occurred in six patients (20%) which was managed in all with a single dose of atropine. CONCLUSION: Thoracic CSE anesthesia can be used effectively for ASA I and II patients undergoing laparoscopic cholecystectomy with significant postoperative benefits. PMID- 27275055 TI - Intrathecal buprenorphine versus fentanyl as adjuvant to 0.75% ropivacaine in lower limb surgeries. AB - BACKGROUND AND AIMS: This study aims to compare the anesthesia characteristics between buprenorphine and fentanyl when added as an adjuvant to intrathecal ropivaciane in an attempt to prolong the duration of spinal anesthesia. MATERIAL AND METHODS: The present prospective double-blind study was undertaken on ninety American Society of Anesthesiologist I and II patients between 18 and 60 years of age undergoing subarachnoid block for lower limb surgery. Group I (n = 30) patients were administered 3 ml of intrathecal solution (2.8 ml of 0.75% ropivacaine + 0.2 ml of isotonic sodium chloride), while Groups II and III patients (n = 30 each) received 2.8 ml 0.75% ropivacaine + 0.2 ml buprenorphine (60 MUg) and 2.8 ml 0.75% ropivacaine + 0.2 ml fentanyl (10 MUg), respectively. Following parameters were observed: Onset times and duration of sensory and motor block, time to first analgesic use, total dose of rescue analgesia, intra- and post-operative pain scores based on visual analog scale, sedation scores, hemodynamic parameters, and side effects if any. Data were analyzed by appropriate statistical tests and P < 0.05 were considered significant. RESULTS: Time to onset of sensory and motor block in all the three groups was comparable. However, duration of sensory block was significantly prolonged in Groups II and III in comparison to Group I (P < 0.05) and it was the longest in Group II (P < 0.05). The duration of motor blockade was similar in all the three groups. The time to first analgesic dose was also significantly prolonged in Groups II and III as compared to Group I (P < 0.05) but was comparable between Groups II and III. Intra- and post-operative hemodynamic parameters, as well as side effects, were comparable. CONCLUSION: Addition of buprenorphine and fentanyl as adjuvants to intrathecal 0.75% ropivacaine prolongs postoperative pain relief without causing any increase in the duration of motor blockade but buprenorphine is better as compared to fentanyl in prolonging the duration of sensory block and achieving a better outcome in terms of pain relief. PMID- 27275056 TI - Effect of dexamethasone in low volume supraclavicular brachial plexus block: A double-blinded randomized clinical study. AB - BACKGROUND AND AIMS: With the use of ultrasound, a minimal effective volume of 20 ml has been described for supraclavicular brachial plexus block. However achieving a long duration of analgesia with this minimal volume remains a challenge. We aimed to determine the effect of dexamethasone on onset and duration of analgesia in low volume supraclavicular brachial plexus block. MATERIAL AND METHODS: Sixty patients were randomly divided into two groups of 30 each. Group C received saline (2 ml) + 20 ml of 0.5% bupivacaine and Group D received dexamethasone (8 mg) + 20 ml of 0.5% bupivacaine in supraclavicular brachial plexus block. Hemodynamic variables and visual analog scale (VAS) score were noted at regular intervals until 450 min. The onset and duration of sensory and motor block were measured. The incidence of "Halo" around brachial plexus was observed. Student's t-test and Chi-square test were used for statistical analysis. RESULTS: The onset of sensory and motor block was significantly earlier in dexamethasone group (10.36 +/- 1.99 and 12 +/- 1.64) minutes compared to control group (12.9 +/- 2.23 and 18.03 +/- 2.41) minutes. The duration of sensory and motor block was significantly prolonged in dexamethasone group (366 +/- 28.11 and 337.33 +/- 28.75) minutes compared to control group (242.66 +/- 26.38 and 213 +/- 26.80) minutes. The VAS score was significantly lower in dexamethasone group after 210 min. "Halo" was present around the brachial plexus in all patients in both the groups. CONCLUSION: Dexamethasone addition significantly increases the duration of analgesia in patients receiving low volume supraclavicular brachial plexus block. No significant side-effects were seen in patients receiving dexamethasone as an adjunct. PMID- 27275057 TI - Comparative efficacy of intravenous dexmedetomidine, clonidine, and tramadol in postanesthesia shivering. AB - BACKGROUND AND AIMS: Postanesthesia shivering continues to be a major challenge in the perioperative care. We compared the efficacy of tramadol, clonidine, and dexmedetomidine in preventing postoperative shivering and its potential adverse effects in patients undergoing laparoscopic cholecystectomy under general anesthesia. MATERIAL AND METHODS: One hundred and twenty American Society of Anesthesiologists I and II patients scheduled for elective laparoscopic cholecystectomy under general anesthesia were divided into four equal groups. Group 1 received clonidine 2 MUg/kg, Group 2 received tramadol 1 mg/kg, Group 3 received dexmedetomidine 1 mcg/kg all intravenous diluted in NS to 5 ml, and Group 4 received NS intravenous 5 ml. Parameters analysed included postoperative blood pressure (BP), pulse rate, respiratory rate (RR), arterial saturation, and tympanic membrane temperature. Patients were observed for shivering episodes, sedation, pain, respiratory depression, nausea, and vomiting. Analysis of variance, Tukey's post-hoc comparison, Chi-square test and Bonferroni post-hoc comparison test were performed using SPSS (Statistical analysis by Statistical Package of Social Sciences of Microsoft Windows) Statistics (version 16.0). RESULTS: The incidence of shivering was 10, 3.3, 13.3 and 40% in Groups 1, 2, 3, and 4 respectively. Patients who were given tramadol had significantly less shivering than patients in clonidine and dexmedetomidine groups (P < 0.01). CONCLUSION: All the three drugs were effective in preventing postoperative shivering. However, tramadol has been found to be more efficacious in preventing postoperative shivering. PMID- 27275058 TI - Intravenous dexmedetomidine versus propofol for intraoperative moderate sedation during spinal anesthesia: A comparative study. AB - BACKGROUND AND AIMS: There has been a paradigm shift of focus toward quality of spinal anesthesia with sedation being an integral aspect of this regional anesthesia technique. Thus, this study was designed to compare efficacy of intravenous dexmedetomidine and propofol for moderate sedation during spinal anesthesia. MATERIAL AND METHODS: A total of 120 patients of age group 18-60 years of American Society of Anesthesiologists grade I & II, posted for surgeries under spinal anesthesia were randomly divided in to three groups (n = 40 each); Group D received infusion of dexmedetomidine 1 MUg/kg over 10 min followed by maintenance infusion of 0.5 MUg/kg/h. Group P received infusion of propofol 6 mg/kg/h for 10 min followed by the infusion maintenance of 2.5 mg/kg/h. Group C (control group) received normal saline. Level of sedation (using observer's assessment of alertness/sedation score), pain intensity (by visual analogue scale), onset and recovery from sedation, hemodynamic changes, and overall patient's satisfaction were assessed. RESULTS: The onset and recovery from sedation were significantly earlier with propofol (15.57 +/- 1.89 min vs. 27.06 +/- 2.26 min; P < 0.001) however intraoperative sedation (level 4), and overall patient's satisfaction was significantly better with dexmedetomidine group (p < 0.05). Duration of postoperative analgesia was significantly prolonged with dexmedetomidine (225.53 +/- 5.61 min vs. 139.60 +/- 3.03 min; P = 0.0013). Mean heart rate and blood pressure were significantly lower in the propofol group (P < 0.05). CONCLUSION: Dexmedetomidine with its stable cardio-respiratory profile, better sedation, overall patient's satisfaction, and analgesia could be a valuable adjunct for intraoperative sedation during spinal anesthesia. PMID- 27275060 TI - Intraperitoneal pre-insufflation of 0.125% bupivaciane with tramadol for postoperative pain relief following laparoscopic cholecystectomy. AB - BACKGROUND AND AIMS: Laparoscopic cholecystectomy is associated with a fairly high incidence of postoperative discomfort which is more of visceral origin than somatic. Studies have concluded that the instillation of local anesthetic with opioid around gall bladder bed provides more effective analgesia than either local anesthetic or opioid alone. MATERIAL AND METHODS: The study included 90 American Society of Anesthesiologists I-II patients of age 16-65 years scheduled for laparoscopic cholecystectomy under general anesthesia. The patients received the study drugs at the initiation of insufflation of CO2 in the intraperitoneal space by the operating surgeon under laparoscopic camera guidance over the gallbladder bed. Patients in Group T received tramadol 2 mg/kg in 30 ml normal saline, in Group B received bupivacaine 30 ml of 0.125% and in Group BT received tramadol 2 mg/kg in 30 ml of 0.125% bupivacaine intraperitoneally. Postoperative pain assessment was done at different time intervals in the first 24 h using Visual Analog Scale of 0-10 (0 = No pain, 10 = Worst pain imagined). Time to first dose of rescue analgesic and total analgesics required in the first 24 h postoperatively were also recorded. The incidence of side effects during the postoperative period was recorded. RESULTS: Reduction in postoperative pain was elicited, at 4 and 8 h postoperatively when Group BT (bupivacaine-tramadol group) was compared with Group T (tramadol group) or Group B (bupivacaine group) (P < 0.01). There was a significantly lower requirement of analgesics during first 24 h postoperatively in Group BT compared to Group B or T but no significant difference in the intake of analgesics was noted between Groups B Group T. Time to first dose of rescue analgesic was also significantly prolonged in Group BT compared to Group B or T. The incidence of nausea and vomiting was comparable in all the study groups. CONCLUSIONS: Intraperitoneal application of bupivacaine with tramadol was a more effective method for postoperative pain control after laparoscopic cholecystectomy compared to intraperitoneal bupivacaine or tramadol alone. PMID- 27275059 TI - Comparison of surgical conditions following premedication with oral clonidine versus oral diazepam for endoscopic sinus surgery: A randomized, double-blinded study. AB - BACKGROUND AND AIMS: Endoscopic sinus surgery (ESS) provides a challenge and an opportunity to the anesthesiologists to prove their mettle and give the surgeons a surgical field which can make their delicate surgery safer,more precise and faster. The aim of the study was to evaluate the surgical field and the rate of blood loss in patients premedicated with oral clonidine versus oral diazepam for endoscopic sinus surgery. MATERIAL AND METHODS: ASA I or II patients who were scheduled to undergo ESS were randomly allocated to group D (n = 30) or group C (n = 30). The patients' vital parameters, propofol infusion rate, and rate of blood loss were observed and calculated. The surgeon, who was blinded, rated the visibility of the surgical field from grade 0-5. RESULTS: In the clonidine group, the rate of blood loss, the surgical time, propofol infusion rate was found to be statistically lower as compared to the diazepam group. Also a higher number of patients in the clonidine group had a better surgical score (better surgical field) than the diazepam group and vice versa. CONCLUSIONS: Premedication with clonidine as compared to diazepam, provides a better surgical field with less blood loss in patients undergoing ESS. PMID- 27275061 TI - Off-pump awake coronary artery bypass grafting under high thoracic epidural anesthesia. AB - Conventionally general anesthesia has been the preferred anesthetic technique for coronary artery bypass grafting (CABG). Ever since the first awake CABG the concept though appearing promising is still being continually evaluated. From the Indian perspective, the practice has been largely limited to certain institutions and seems to be not widely practiced across India. This case reports our experience with this technique from the western part of the country. PMID- 27275062 TI - Epidural chloroprocaine bolus in emergency cesarean section-lessons learned from a near mishap. AB - Administration of a large bolus of epidural chloroprocaine to hasten the spread of anesthesia is an accepted practice during emergency cesarean section. Occasionally, this practice can result in a very high block that can compromise patient's safety. We describe a case of epidural chloroprocaine administration in a 4 point position resulting in a high dermatomal block requiring respiratory assistance. Events surrounding the case are discussed, with a view to warn the reader about the pitfalls of such a practice. PMID- 27275063 TI - Supraglottic airway and caudal epidural for anesthetic management of a child with Larsen syndrome. PMID- 27275064 TI - Difficult airway: When deliberate is too close to improvisation. PMID- 27275065 TI - Spinal anesthesia and direction of spinal needle bevel. PMID- 27275066 TI - Thoracic combined spinal epidural anesthesia in patient of dilated cardiomyopathy undergoing laparoscopic cholecystectomy. PMID- 27275067 TI - Anesthetic management of a rare case of Takayasu's arteritis posted for total abdominal hysterectomy. PMID- 27275068 TI - Pneumocephalus after epidural analgesia: Should loss of resistance with air be blown out? PMID- 27275069 TI - Heparin resistance during pediatric cardiac surgery: An unanticipated challenge for an anesthesiologist. PMID- 27275070 TI - A case of postpartum lateral sinus thrombosis following cesarean section under spinal anesthesia. PMID- 27275071 TI - Worldwide contribution of Indian authors in various anesthesia-related journals. PMID- 27275072 TI - Vaporizer interlock malfunctioning. PMID- 27275073 TI - Comparison of suction above cuff and standard endotracheal tubes in neurological patients for the incidence of ventilator-associated pneumonia and in-hospital outcome: A randomized controlled pilot study. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) is a common complication with endotracheal intubation. The occurrence of VAP results in significant mortality and morbidity. Earlier studies have shown reduction in the incidence of VAP with subglottic secretion drainage. The incidence of VAP in neurologically injured patients is higher and can impact the neurological outcome. This study aimed to compare the incidence of VAP with standard endotracheal tube (SETT) and suction above cuff endotracheal tube (SACETT) in neurologically ill patients and its impact on clinical outcome. METHODS: Fifty-four patients with neurological illnesses aged >=18 years and requiring intubation and/or ventilation and anticipated to remain on ETT for >=48 h were randomized to receive either SETT or SACETT. All the VAP preventive measures were similar between two groups except for the difference in type of tube. RESULTS: The data of 50 patients were analyzed. The incidence of clinical VAP was 20% in SETT group and 12% in SACETT group; (P = 0.70). The incidence of microbiological VAP was higher in the SETT group (52%) as compared to SACETT group (44%) but not statistically significant; (P = 0.78). There was no difference between the two groups for measured outcomes such as duration of intubation, mechanical ventilation, and Intensive Care Unit stay. CONCLUSIONS: In this pilot study in neurological population, a there was no significant difference in incidence of clinical and microbiological VAP was seen between SETT and SACETT, when other strategies for VAP prevention were similar. Other outcomes were similar with use of either tube for intubation. PMID- 27275074 TI - Oral care practices for patients in Intensive Care Units: A pilot survey. AB - OBJECTIVE: To assess the level of knowledge and difficulties concerning hospitalized patients regarding preventive oral health measures among professionals working in Intensive Care Units (ICUs). STUDY POPULATION AND METHODS: A cross-sectional survey was conducted among 71 health professionals working in the ICU. A self-administered questionnaire was used to determine the methods used, frequency, and attitude toward oral care provided to patients in Brazilian ICUs. The variables were analyzed using descriptive statistics (percentages). A one-sample t-test between proportions was used to assess significant differences between percentages. t-statistics were considered statistically significant for P < 0.05. Bonferroni correction was applied to account for multiple testing. RESULTS: Most participants were nursing professionals (80.3%) working 12-h shifts in the ICU (70.4%); about 87.3% and 66.2% reported having knowledge about coated tongue and nosocomial pneumonia, respectively (P < 0.05). Most reported using spatulas, gauze, and toothbrushes (49.3%) or only toothbrushes (28.2%) with 0.12% chlorhexidine (49.3%) to sanitize the oral cavity of ICU patients (P < 0.01). Most professionals felt that adequate time was available to provide oral care to ICU patients and that oral care was a priority for mechanically ventilated patients (80.3% and 83.1%, respectively, P < 0.05). However, most professionals (56.4%) reported feeling that the oral cavity was difficult to clean (P < 0.05). CONCLUSION: The survey results suggest that additional education is necessary to increase awareness among ICU professionals of the association between dental plaque and systemic conditions of patients, to standardize oral care protocols, and to promote the oral health of patients in ICUs. PMID- 27275075 TI - Antimicrobial agents' utilization and cost pattern in an Intensive Care Unit of a Teaching Hospital in South India. AB - BACKGROUND AND AIMS: High utilization and inappropriate usage of antimicrobial agents (AMAs) in an Intensive Care Unit (ICU) increases resistant organisms, morbidity, mortality, and treatment cost. Prescription audit and active feedback are a proven method to check the irrational prescription. Measuring drug utilization in DDD/100 bed-days is proposed by the WHO to analyze and compare the utilization of drugs. Data of AMAs utilization are required for planning an antibiotic policy and for follow-up of intervention strategies. Hence, in this study, we proposed to evaluate the utilization pattern and cost analysis of AMA used in the ICU. METHODOLOGY: A prospective observational study was conducted for 1 year from January 1, 2014, to December 31, 2014, and the data were obtained from the ICU of a tertiary care hospital. The demographic data, disease data, relevant investigation, the utilization of different classes of AMAs (WHO-ATC classification) as well as individual drugs and their costs were recorded. RESULTS: One thousand eight hundred and sixty-two prescriptions of AMAs were recorded during the study period with an average of 1.73 +/- 0.04 prescriptions/patient. About 80.4% patients were prescribed AMAs during admission. Ceftriaxone (22.77%) was the most commonly prescribed AMA followed by piperacillin/tazobactam (15.79%), metronidazole (12%), amoxicillin/clavulanic acid (6.44%), and azithromycin (4.34%). Ceftriaxone, piperacillin/tazobactam, metronidazole, and linezolid were the five maximally utilized AMAs with 38.52, 19.22, 14.34, 8.76, and 8.16 DDD/100 bed-days respectively. An average cost of AMAs used per patient was 2213 Indian rupees (INR). CONCLUSION: A high utilization of AMAs and a high cost of treatment were noticed which was comparable to other published data, though an increased use of newer AMAs such as linezolid, clindamycin, meropenem, colistin was noticed. PMID- 27275076 TI - Tracheostomy in special groups of critically ill patients: Who, when, and where? AB - Tracheostomy is one of the most common procedures undertaken in critically ill patients. It offers many theoretical advantages over translaryngeal intubation. Recent evidence in a heterogeneous group of critically ill patients, however, has not demonstrated a benefit for tracheostomy, in terms of mortality, length of stay in Intensive Care Unit (ICU), or incidence of ventilator-associated pneumonia. It may be a beneficial intervention in articular subsets of ICU patients. In this article, we will focus on the evidence for the timing of tracheostomy and its effect on various subgroups of patients in critical care. PMID- 27275077 TI - Exploration of eosinopenia as a diagnostic parameter to differentiate sepsis from systemic inflammatory response syndrome: Results from an observational study. AB - AIM OF THE STUDY: Initial differentiation of sepsis from systemic inflammatory response syndrome (SIRS) is of prime importance for early institution of appropriate treatment. This study aimed to compare the differential diagnostic efficacy of absolute eosinophil count (AEC - a routinely available economic marker) with total leukocyte count (TLC) and procalcitonin (PCT - a costly marker available only in specialized settings). MATERIALS AND METHODS: In this prospective observational study, 170 patients of sepsis (severe sepsis = 125; SIRS = 45) were enrolled. AEC, TLC, and PCT were measured in the blood of all patients at the time of admission and data analyzed statistically. RESULTS: Median AEC was 0 cells/mm(3) in both SIRS and sepsis. TLC and PCT levels were significantly higher (P < 0.001) in culture negative, culture positive, and overall sepsis groups in comparison to SIRS group. At a cutoff of < 50 cells/mm(3), AEC demonstrated a sensitivity and specificity of 23% and 68%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of TLC were 57%, 71%, 85%, 37% and of PCT were 82.4%, 82.2%, 93%, and 63%, respectively with area under curve of 0.455 for AEC, 0.640 for TLC, 0.908 for PCT. CONCLUSIONS: This study suggests that eosinopenia is not a reliable diagnostic tool to differentiate sepsis from SIRS. PCT and TLC are better differential diagnostic biomarkers. PMID- 27275078 TI - Evaluation of antibiotic use in Pediatric Intensive Care Unit of a developing country. AB - BACKGROUND: Pediatric Intensive Care Unit (PICU) patients are often prescribed antibiotics with a low threshold in comparison to patients elsewhere. Irrational antibiotics use can lead to rapid emergence of drug resistance, so surveillance of their use is important. OBJECTIVES: To evaluate the use of antibiotics in relation to bacteriological findings in PICU of a Tertiary Hospital. METHODS: Retrospective review of medical records of all children (age 1 month-16 years) admitted in our closed multidisciplinary-cardiothoracic PICU from January to June 2013 was performed, after approval from Ethical Review Committee. For each antibiotic, indication (prophylactic, empiric, therapeutic) and duration of use were recorded. All diagnoses of infections were recorded according to diagnostic criteria of IPSCC 2005. Results are presented as frequency and percentages and median with inter quartile range using SPSS version 19. RESULTS: All of the total 240 patients admitted in PICU during the study period received antibiotics: 43% (n = 104) prophylactically, 42% (n = 102) empirically, and 15% (n = 15) therapeutically. Median number of antibiotic use per patient in PICU was 3, with range of 1-7. 25% received 1 antibiotic, 23% received 2 antibiotics, 29% received 3 antibiotics, and rest received >=4 antibiotics. Most commonly used antibiotics were cefazolin, meropenem, vancomycin and ceftriaxone, and most frequently used combination was meropenem and vancomycin. In majority of the cases, (70%) empiric antibiotic combinations were stopped in 72 h. CONCLUSION: This is the first report of antibiotics use in PICU from our country, which shows that antibiotics are prescribed universally in our PICU. Strategies to assess the need for antibiotic use are needed. PMID- 27275079 TI - Extracorporeal treatment with high-volume continuous venovenous hemodiafiltration and charcoal-based sorbent hemoperfusion for severe metformin-associated lactic acidosis. AB - We present a case of a 49-year-old female with an alleged history of ingestion of approximately 100 tablets of metformin (850 mg each). Investigations revealed severe lactic acidosis with lactate levels of 13.5 mmol/L and pH of 7.17. This indicates severe toxicity and is associated with a high mortality. Charcoal-based sorbent hemoperfusion was done as a desperate effort, as patient continued to deteriorate despite supportive care and high-volume continuous venovenous hemodiafiltration. The patient survived despite metformin-associated lactic acidosis related to severe metformin toxicity. PMID- 27275080 TI - A rare complication of tracheal intubation. AB - Accidental endobronchial intubation is a frequent complication in critically ill patients requiring tracheal intubation (TI). If such complication occurs, it is more often the right main bronchus that is intubated due to anatomical reasons. Left main bronchus (LMB) intubation is rare. Here, we report a case with auscultatory, bronchoscopic, and radiographic evidence of accidental LMB intubation in a pregnant woman with dengue shock syndrome. We highlight this case to increase awareness about this possible-but-rare complication of TI. PMID- 27275081 TI - Spontaneous arterial hemorrhage as a complication of dengue. AB - Bleeding complications of dengue hemorrhagic fever such as epistaxis, gum bleeding, gastrointestinal bleeding, hypermenorrhea, hematuria, and thrombocytopenia have been documented. A 49-year-old female presented with complaints of intermittent high-grade fever for the past 4 days, lower abdominal pain and altered sensorium for 1 day. Laboratory investigations revealed severe anemia, mild thrombocytopenia, hypofibrinogenemia, and positive dengue serology. Emergency ultrasound examination of the abdomen revealed a possible rapidly expanding hematoma from the inferior epigastric artery and suggested urgent computed tomography (CT) angiogram for confirmation of the same. CT angiogram was confirmatory, and patient underwent emergency embolization of the right inferior epigastric artery. We report the first case of inferior epigastric hemorrhage and rectus sheath hematoma as a consequence of dengue. PMID- 27275082 TI - Statin-induced rhabdomyolysis in patient with renal failure and underlying undiagnosed hypothyroidism. AB - Rhabdomyolysis is a syndrome characterized by muscle necrosis which causes the release of myoglobin into the bloodstream. The manifestations of this syndrome range from asymptomatic elevation of serum muscle enzymes to life-threatening cases associated with extremely high enzyme levels, electrolyte imbalance, and acute renal failure. Symptoms of rhabdomyolysis include dark urine, muscle weakness, and fatigue. Statins are commonly used drugs for the prevention and management of dyslipidemia. We present an interesting and critical case on statin induced rhabdomyolysis with renal failure and previously undiagnosed idiopathic hypothyroidism. PMID- 27275083 TI - Dying within dying: Ethical dilemmas of treating terminally ill patients with acute life-threatening illnesses. PMID- 27275084 TI - Scorpion bite, a sting to the heart! PMID- 27275085 TI - An aberrantly positioned central venous catheter: A presage of an underlying anatomical anomaly. PMID- 27275086 TI - Mid-term assessment of the decade of action for road safety: Progress made, yet at a slow rate. PMID- 27275087 TI - Another cutaneous sign of acute pancreatitis. PMID- 27275088 TI - Surgical dilemmas in the management of colorectal liver metastases: The role of timing. AB - Colorectal cancer (CRC) is an emerging health problem in the Western World both for its raising tendency as well as for its metastatic potential. Almost half of the patients with CRC will develop liver metastases during the course of their disease. The liver surgeon dealing with colorectal liver metastases faces several surgical dilemmas especially in the setting of the timing of operation. Synchronous resectable metastases should be treated prior or after induction chemotherapy? Furthermore in the case of synchronous colorectal liver metastases which organ should we first deal with, the liver or the colon? All these questions are set in the editorial and impulse for further investigation is put focusing on multidisciplinary approach and individualization of treatment modalities. PMID- 27275089 TI - How important is donor age in liver transplantation? AB - The age of liver donors has been increasing in the past several years because of a donor shortage. In the United States, 33% of donors are age 50 years or older, as are more than 50% in some European countries. The impact of donor age on liver transplantation (LT) has been analyzed in several studies with contradictory conclusions. Nevertheless, recent analyses of the largest databases demonstrate that having an older donor is a risk factor for graft failure. Donor age is included as a risk factor in the more relevant graft survival scores, such as the Donor Risk Index, donor age and Model for End-stage Liver Disease, Survival Outcomes Following Liver Transplantation, and the Balance of Risk. The use of old donors is related to an increased rate of biliary complications and hepatitis C virus-related graft failure. Although liver function does not seem to be significantly affected by age, the incidence of several liver diseases increases with age, and the capacity of the liver to manage or overcome liver diseases or external injuries decreases. In this paper, the importance of age in LT outcomes, the role of donor age as a risk factor, and the influence of aging on liver regeneration are reviewed. PMID- 27275090 TI - Current status of laparoscopic and robotic ventral mesh rectopexy for external and internal rectal prolapse. AB - External and internal rectal prolapse with their affiliated rectocele and enterocele, are associated with debilitating symptoms such as obstructed defecation, pelvic pain and faecal incontinence. Since perineal procedures are associated with a higher recurrence rate, an abdominal approach is commonly preferred. Despite the description of greater than three hundred different procedures, thus far no clear superiority of one surgical technique has been demonstrated. Ventral mesh rectopexy (VMR) is a relatively new and promising technique to correct rectal prolapse. In contrast to the abdominal procedures of past decades, VMR avoids posterolateral rectal mobilisation and thereby minimizes the risk of postoperative constipation. Because of a perceived acceptable recurrence rate, good functional results and low mesh-related morbidity in the short to medium term, VMR has been popularized in the past decade. Laparoscopic or robotic-assisted VMR is now being progressively performed internationally and several articles and guidelines propose the procedure as the treatment of choice for rectal prolapse. In this article, an outline of the current status of laparoscopic and robotic ventral mesh rectopexy for the treatment of internal and external rectal prolapse is presented. PMID- 27275091 TI - Multiorgan chronic inflammatory hepatobiliary pancreatic murine model deficient in tumor necrosis factor receptors 1 and 2. AB - AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues. METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naive animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological changes were examined postmortem in tissues. Collagen accumulation and fibrosis were confirmed with Sirius Red staining. RESULTS: Animals lost weight after oral administration of DBTC and developed persistent inflammatory abdominal and hindpaw hypersensitivity compared to sham-treated controls (P < 0.0001). These pain related secondary mechanical hypersensitivity responses increased more than 2-fold in DBTC-treated animals. The drastically diminished rearing and grooming rates persisted after DBTC administration throughout the study. Gross as well as micropathology at one month confirmed that animals treated with DBTC developed chronic hepatobiliary injuries evidenced with activation of stellate cells, multifocal necrosis, fatty degeneration of hepatocytes, periportal infiltration of inflammatory cells, and prominent biliary ductal dilation. The severity of hepatitis was scored 3.7 +/- 0.2 (severe) in DBTC-treated animals vs score 0 (normal) in sham-treated animals. Fibrotic thickening was extensive around portal ducts, in hepatic parenchyma as well as in lobular pancreatic structures and confirmed with Sirius Red histopathology. In addition, pancreatic microarchitecture was presented with distortion of islets, and parenchyma, infiltration of inflammatory cells, degeneration, vacuolization, and necrosis of acinar cells and distention of pancreatic ducts. Extent of pancreatic damage and pancreatitis were scored 3.6 +/ 0.4 (severe) for DBTC-treated in contrast to score 0 (normal) in sham-treated animals. The gall bladder became expanded with ductal distention, and occasional bile stones were detected along with microscopic hepatic lesions. DBTC-treated animals developed splenic hypertrophy with increased weight and length (P < 0.01) along with thymic atrophy (P < 0.001). Finally, colitic lesions and colitis were prominent in DBTC-treated animals and scored 3.4 +/- 0.3 (moderately severe) vs 0 (normal) for the sham-treated animals. CONCLUSION: This is the first report of chronic inflammatory multiorgan hepatobiliary pancreatitis, along with fibrosis and calculi formation induced reliably utilizing oral DBTC administration in TNFR1/R2 deficient mice. PMID- 27275092 TI - Phosalone-induced inflammation and oxidative stress in the colon: Evaluation and treatment. AB - AIM: To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid (EA) as a remedy. METHODS: In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given (1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received (1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers. RESULTS: The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a (TNF-alpha), interlukin-6beta (IL-6beta) and nuclear factor (NF)-kappaB proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF alpha (230.47 +/- 16.55 pg/mg protein vs 546.43 +/- 45.24 pg/mg protein, P < 0.001), IL-6beta (15.85 +/- 1.03 pg/mg protein vs 21.55 +/- 1.3 pg/mg protein, P < 0.05), and NF-kappaB (32.47 +/- 4.85 pg/mg protein vs 51.41 +/- 0.71 pg/mg protein, P < 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone's side effects, it improved the level of AChE activity (48.5% +/- 6% vs 25% +/- 7%, P < 0.05), TTM (0.391 +/- 0.008 mmol/L vs 0.249 +/- 0.032 mmol/L, P < 0.05), FRAP (46.04 +/- 5.005 MUmol/L vs 18.22 +/- 1.9 MUmol/L, P < 0.01) and MPO (0.222 +/- 0.019 U/mg protein vs 0.387 +/- 0.04 U/mg protein, P < 0.05). CONCLUSION: This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins. PMID- 27275093 TI - CdSe/ZnS quantum dots induce photodynamic effects and cytotoxicity in pancreatic cancer cells. AB - AIM: To investigate the photodynamic effect of CdSe/ZnS quantum dots (QDs) on pancreatic cancer cells and elucidate the probable mechanisms. METHODS: The pancreatic cancer cell line SW1990 was treated with different concentrations of CdSe/ZnS QDs (0, 0.5, 1.0, 1.5, 2.0, 2.5 MUmol/L), with or without illumination. The viability of SW1990 cells was tested using the Cell Counting Kit-8 (CCK-8) assay. The ultrastructural changes of SW1990 cells were observed by transmission electron microscopy. Apoptosis was detected by nuclear staining and flow cytometry (FCM). Reactive oxygen species (ROS) were measured by dichlorofluorescein diacetate via fluorescence microscopy. Expression of Bax, Bcl 2 and caspase-3 was measured by real-time polymerase chain reaction (PCR) and protein immunoblotting 24 h after SW1990 cells were treated with CdSe/ZnS QDs and illuminated. RESULTS: The CCK-8 assay results showed that both CdSe/ZnS QDs with and without illumination suppressed SW1990 cell proliferation. Cell viability was significantly lower when illuminated or with a longer incubation time and a higher light dose. CdSe/ZnS QDs with illumination caused ultrastructural changes in SW1990 cells, such as organelle degeneration and chromatin condensation and aggregation at the periphery of the nucleus. Fluorescence microscopy and FCM showed that CdSe/ZnS QDs (1.5 MUmol/L) with illumination increased SW1990 cell apoptosis (53.2%) and ROS generation compared with no illumination. Real-time PCR showed that expression of Bax and caspase-3 was upregulated and Bcl-2 was downregulated. Immunoblotting results were consistent with real-time PCR results. Inhibition of ROS and apoptosis both attenuated QD-photodynamic-therapy-induced cell death. CONCLUSION: CdSe/ZnS QDs can be used as a photosensitizer to inhibit SW1990 cell proliferation through ROS generation and apoptotic protein expression regulation. PMID- 27275094 TI - Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice. AB - AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP) associated lung injury and the possible signaling pathway involved. METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05). CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway. PMID- 27275095 TI - (125)I-labeled anti-bFGF monoclonal antibody inhibits growth of hepatocellular carcinoma. AB - AIM: To investigate the inhibitory efficacy of (125)I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC). METHODS: bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with (125)I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of (125)I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), (125)I-bFGF mAb, (125)I plus bFGF mAb, bFGF mAb, or (125)I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction. RESULTS: The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 degrees C. After coupling, (125)I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 degrees C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, (125)I, bFGF mAb, (125)I plus bFGF mAb, and (125)I-bFGF mAb groups was 1.88 +/- 0.25, 1.625 +/- 0.21, 1.5 +/- 0.18, 1.41 +/- 0.16, and 0.98 +/- 0.11 g, respectively. The tumor inhibition ratio in the (125)I, bFGF mAb, (125)I plus bFGF mAb, and (125)I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the (125)I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the (125)I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for (125)I group) compared with the control group. CONCLUSION: (125)I-bFGF mAb inhibits growth of HCC xenografts. The coupling effect of (125)I-bFGF mAb is more effective than the concomitant use of (125)I and bFGF mAb. PMID- 27275096 TI - Transarterial administration of integrin inhibitor loaded nanoparticles combined with transarterial chemoembolization for treating hepatocellular carcinoma in a rat model. AB - AIM: To compare the effect of transarterial chemoembolization (TACE) plus GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro, integrin-inhibitor) loaded nanoparticles with TACE alone or TACE + GRGDSP in a rat model of liver tumor. METHODS: Morris hepatoma 3924A tumors were implanted in the livers of 30 ACI rats. The ACI rats were divided randomly into three groups (10 animals each). Tumor volume before treatment (V1) was examined by magnetic resonance imaging (MRI), and then, after laparotomy and placement of a PE-10 catheter into the hepatic artery, the following interventional protocols were performed: TACE (mitomycin C + lipiodol + degradable starch microspheres) + GRGDSP loaded nanoparticles for group A; TACE + GRGDSP for group B (control group 1); TACE alone for group C (control group 2). Tumor volume (V2) was assessed by MRI and the mean ratio of the post-treatment to pretreatment tumor volumes (V2/V1) was calculated. Immunohistochemical analysis was performed to assess the quantification of matrix metalloprotein 9 (MMP-9) and vascular endothelial growth factor (VEGF) positive tumor cells in each treatment group. RESULTS: The mean tumor growth ratios (V2/V1) were 1.3649 +/- 0.1194 in group A, 2.0770 +/- 0.1595 in group B, and 3.2148 +/- 0.1075 in group C. Compared with groups B and C, group A showed a significant reduction in tumor volume. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C. The angiogenesis of tumor was evaluated using anti-VEGF antibodies, and the metastasis of tumor was assessed using anti-MMP-9 antibody. MMP-9 and VEGF were expressed in all specimens. The immunoexpression of these proteins was confirmed by the presence of red cytoplasmic staining in tumor cells. Lower expression of MMP-9 and VEGF in hepatocellular carcinoma was observed in group A than in groups B and C. CONCLUSION: Transarterial administration of integrin inhibitor loaded nanoparticles combined with TACE evidently retards tumor growth and intrahepatic metastases compared with TACE alone or TACE plus integrin inhibitor in an animal model of hepatocellular carcinoma. PMID- 27275097 TI - Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity. AB - AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers. METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 degrees C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria. RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 MUg/g in 2 participants, and above 50 MUg/g in a further 5 participants. CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins. PMID- 27275098 TI - Serum Helicobacter pylori KatA and AhpC antibodies as novel biomarkers for gastric cancer. AB - AIM: To investigate catalase (KatA) and alkyl hydroperoxide reductase (AhpC) antibodies of Helicobacter pylori as biomarkers for gastric cancer (GC). METHODS: This study included 232 cases and 264 controls. Recombinant KatA and AhpC proteins were constructed and the levels of antibodies were tested by indirect enzyme-linked immunosorbent assay (ELISA). Logistic regression was applied to analyze the relationships between KatA, AhpC and GC. The chi(2) trend test was used to evaluate the dose-response relationships between serum KatA and AhpC antibody levels and GC. Receiver operating characteristic (ROC) curve was used to evaluate the screening accuracy of KatA and AhpC as biomarkers. Combined analysis was used to observe screening accuracy of predictors for GC. RESULTS: In all subjects, the association between KatA and AhpC and GC risk was significant (P < 0.001) with odds ratio (OR) = 12.84 (95%CI: 7.79-21.15) and OR = 2.4 (95%CI: 1.55 3.73), respectively. KatA and AhpC antibody levels were strongly related to GC risk with a dose-dependent effect (P for trend < 0.001). The area under the ROC (AUC) for KatA was 0.806, providing a sensitivity of 66.81% and specificity of 86.36%; and the AUC for AhpC was 0.615, with a sensitivity of 75.65% and specificity of 45.49%. The AUC was 0.906 for KatA and flagella protein A (FlaA) combined analysis. CONCLUSION: Serum KatA and AhpC antibodies are associated with GC risk and KatA may serve as a biomarker for GC. KatA/FlaA combined analysis improved screening accuracy. PMID- 27275099 TI - Endoscopy-based management decreases the risk of postoperative recurrences in Crohn's disease. AB - AIM: To investigate whether an endoscopy-based management could prevent the long term risk of postoperative recurrence. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients (follow up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95%CI: 0.25 0.66, P < 0.001) and surgical postoperative recurrence (HR = 0.30, 95%CI: 0.13 0.70, P = 0.006). CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation. PMID- 27275100 TI - Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse. AB - AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results. METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results. RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations <= 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23). CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk. PMID- 27275101 TI - Blood neutrophil-lymphocyte ratio predicts survival after hepatectomy for hepatocellular carcinoma: A propensity score-based analysis. AB - AIM: To investigate whether an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) can predict poor survival in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 526 patients with HCC who underwent surgery between 2004 and 2011. RESULTS: Preoperative NLR >= 2.81 was an independent predictor of poor disease-free survival (DFS, P < 0.001) and overall survival (OS, P = 0.044). Compared with patients who showed a preoperative NLR < 2.81 and postoperative increase, patients who showed preoperative NLR >= 2.81 and postoperative decrease had worse survival (DFS, P < 0.001; OS, P < 0.001). Among patients with preoperative NLR >= 2.81, survival was significantly higher among those showing a postoperative decrease in NLR than among those showing an increase (DFS, P < 0.001; OS, P < 0.001). When elevated, alpha-fetoprotein (AFP) provided no prognostic information, and so preoperative NLR >= 2.81 may be a good complementary indicator of poor OS whenever AFP levels are low or high. CONCLUSION: Preoperative NLR >= 2.81 may be an indicator of poor DFS and OS in patients with HCC undergoing surgery. Preoperative NLR >= 2.81 may be a good complementary indicator of poor OS when elevated AFP levels provide no prognostic information. PMID- 27275102 TI - Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease. AB - AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 +/- 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-alpha levels were associated independently with steatosis grade of more than 33% [beta = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [beta = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003 1.15), P < 0.05]. Similarly, higher TNF-alpha, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [beta = 1.06 (95%CI: 1.002 1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-alpha values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [beta = 1.05 (95%CI: 1.01 1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately. PMID- 27275103 TI - Usefulness of portal vein pressure for predicting the effects of tolvaptan in cirrhotic patients. AB - AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention. METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response. RESULTS: Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 * 10(-6)) and -1.3 kg (P = 1.83 * 10(-5)), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 * 10(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors. CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure. PMID- 27275104 TI - Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial. AB - AIM: To determine the efficacy of rectally administered naproxen for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: This double-blind randomized control trial conducted from January 2013 to April 2014 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 324 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients received a single dose of Naproxen (500 mg; n = 162) or a placebo (n = 162) per rectum immediately before ERCP. The overall incidence of PEP, incidence of mild to severe PEP, serum amylase levels and adverse effects were measured. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and elevation of the serum amylase level to > 3 * the upper normal limit (60-100 IU/L) within 24 h after ERCP. The severity of PEP was classified according to the duration of therapeutic intervention for PEP: mild, 2-3 d; moderate 4-10 d; and severe, > 10 d and/or necessitated surgical or intensive treatment, or contributed to death. RESULTS: PEP occurred in 12% (40/324) of participants, and was significantly more frequent in the placebo group compared to the naproxen group (P < 0.01). Of the participants, 25.9% (84/324) developed hyperamylasemia within 2 h of procedure completion, among whom only 35 cases belonged to the naproxen group (P < 0.01). The incidence of PEP was significantly higher in female sex, in patients receiving pancreatic duct injection, more than 3 times pancreatic duct cannulations, and ERCP duration more than 40 min (Ps < 0.01). There were no statistically significant differences between the groups regarding the procedures or factors that might increase the risk of PEP, sphincterotomy, precut requirement, biliary duct injection and number of pancreatic duct cannulations. In the subgroup of patients with pancreatic duct injection, the rate of pancreatitis in the naproxen group was significantly lower than that in the placebo (6 patients vs 23 patients, P < 0.01, RRR = 12%, AR = 0.3, 95%CI: 0.2-0.6). Naproxen reduced the PEP in patients with >= 3 pancreatic cannulations (P < 0.01, RRR = 25%, AR = 0.1, 95%CI: 0.1-0.4) and an ERCP duration > 40 min (P < 0.01, RRR = 20%, AR = 0.9, 95%CI: 0.4-1.2). CONCLUSION: Single dose of suppository naproxen administered immediately before ERCP reduces the incidence of PEP. PMID- 27275105 TI - Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit. AB - AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) in adults and to identify factors that influence these outcomes. METHODS: We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT. RESULTS: A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38 (95%CI: 0.23-0.53, P < 0.001). Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation (SMD: 0.57 vs 0.22, P < 0.01) and in studies with high vs low study quality (SMD: 0.45 vs 0.00, P = 0.01). Constipation (R (2) = 38%, P < 0.01), higher study quality (R (2) = 31%, P = 0.01), older age (R (2) = 27%, P = 0.02), higher percentage of female subjects (R (2) = 26%, P = 0.02), and fewer probiotic strains (R (2) = 20%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019 (SMD: 0.67, P < 0.001) and B. lactis DN-173 010 (SMD: 0.54, P < 0.01) while other probiotic strains yielded negligible reductions in ITT relative to control. CONCLUSION: Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains. PMID- 27275108 TI - Separation and purification and in vitro anti-proliferative activity of leukemia cell K562 of Galium aparine L. petroleum ether phase. AB - To explore material basis of in vitro anti-proliferative activity of leukemia cell K562 of petroleum ether phase of product resulting from Galium aparine L. 60% ethanol extraction, the experiment adopts column chromatography combined with thin layer preparation, isolates and purifies petroleum ether, conducts structural identification of obtained single compound and applies MTT method for viability assay of in vitro anti-proliferative activity of leukemia cell K562. Experimental results show that G. aparine L. petroleum ether contains mainly beta sitosterol, daucosterol and dibutyl phthalate and other substances. Under experimental conditions, the three could inhibit the proliferation of leukemia cell K562 with dose-effect and time-effect relationship, of which dibutyl phthalate has strongest activity. Dibutyl phthalate with excellent activity, beta sitosterol with rich content and moderate effect should be the main contributor to its biological activity. PMID- 27275106 TI - Modified single transluminal gateway transcystic multiple drainage technique for a huge infected walled-off pancreatic necrosis: A case report. AB - We report a successful endoscopic ultrasonography-guided drainage of a huge infected multilocular walled-off necrosis (WON) that was treated by a modified single transluminal gateway transcystic multiple drainage (SGTMD) technique. After placing a wide-caliber fully covered metal stent, follow-up computed tomography revealed an undrained subcavity of WON. A large fistula that was created by the wide-caliber metal stent enabled the insertion of a forward viewing upper endoscope directly into the main cavity, and the narrow connection route within the main cavity to the subcavity was identified with a direct view, leading to the successful drainage of the subcavity. This modified SGTMD technique appears to be useful for seeking connection routes between subcavities of WON in some cases. PMID- 27275107 TI - Natural cures for breast cancer treatment. AB - For centuries, herbs and plants have been used for medicinal purposes and as food as well. This review concerns about different types of plants that retain the immune stimulating and anti-tumor properties. Large variety of active phytochemicals such as carotenoids, flavonoids, ligands, polyphenolics, terpenoids, sulfides, lignans and plant sterols has been identified in different types of herbs. These phytochemicals have different mechanisms of action. They either stimulate the protective enzyme like glutathione transferase or prevent the cell proliferation. This review has centered on the biochemical properties of Allium sativum, Echinacea, Curcuma longa, Arctium lappa, Camellia sinensis, Panax ginseng and Flax seed. Extracts and juices of Withania somnifera, Amoora rohituka, Dysoxylum binectariferum and Vaccinium macrocarpon, respectively also used as anti-breast cancer. The volatile oils and extracts of these herbs and plants inhibit the synthesis of mevalonate that lessen the tumor growth and cholesterol synthesis. PMID- 27275109 TI - Release property study on the novel divalproex sodium enteric-coated capsules. AB - In the present study, a novel divalproex sodium (DS) enteric-coated capsule was prepared, and high performance liquid chromatography (HPLC) assay method for DS was developed. Their uniformity, release curve and release characteristics in different solvents were examined. The release studies were performed using marketed sample as a reference and data were analyzed in terms of cumulative release amounts as a function of time. It was demonstrated by the results that assay developed was specific, rapid and reliable, which can be used to determine DS in vitro accurately, and our developed samples were similar to reference preparation in in vitro release characteristics. The release characteristics of different batches of samples were quite similar to each other, and the total release percents of DS from enteric-coated capsule were within 0-10% in HCl, and reached close to 100% in phosphate buffer. Similarity factors (f 2) of three batches between two preparations were all higher than 50. The developed enteric coated capsule may be a promising alternative dosage form for treatment of related diseases. PMID- 27275110 TI - Study on fluorouracil-chitosan nanoparticle preparation and its antitumor effect. AB - To successfully prepare fluorouracil-chitosan nanoparticles, and further analyze its anti-tumor activity mechanism, this paper makes a comprehensive study of existing preparation prescription and makes a detailed analysis of fluorouracil chitosan in vitro release and pharmacodynamic behavior of animals. Two-step synthesis method is adopted to prepare 5-FU-CS-mPEG prodrugs, and infrared, (1)H NMR and differential thermal analysis are adopted to analyze characterization synthetic products of prepared drugs. To ensure clinical efficacy of prepared drugs, UV spectrophotometry is adopted for determination of drug loading capacity of prepared drugs, transmission electron microscopy is adopted to observe the appearance, dynamic dialysis method is used to observe in vitro drug release of prepared drugs and fitting of various release models is done. Anti-tumor effect is studied via level of animal pharmacodynamics. After the end of the experiment, tumor inhibition rate, spleen index and thymus index of drugs are calculated. Experimental results show that the prepared drugs are qualified in terms of regular shape, dispersion, drug content, etc. Animal pharmacodynamics experiments have shown that concentration level of drug loading capacity of prepared drugs has a direct impact on anti-tumor rate. The higher the concentration, the higher the anti-tumor rate. Results of pathological tissue sections of mice show that the prepared drugs cause varying degrees of damage to receptor cells, resulting in cell necrosis or apoptosis problem. It can thus be concluded that ion gel method is an effective method to prepare drug-loading nanoparticles, with prepared nanoparticles evenly distributed in regular shape which demonstrate good slow-release characteristics in receptor vitro and vivo. At the same time, after completion of drug preparation, relatively strong anti-tumor activity can be generated for the receptor, so this mode of preparation enjoys broad prospects for development. PMID- 27275111 TI - Preparation and application of functionalized nano drug carriers. AB - OBJECTIVE: Targeting at category memory characteristics and preparation methods of functionalized nano drugs, preparation technology of functionalized nano drug carriers is studied, and then important role of functionalized nano drug carrier in preparation of medicine is studied. METHODS: Carry out the relevant literature search with computer, change limited language in the paper to Chinese and necessarily remove repetitive studies. RESULTS: After first review of 1260 retrieved literature, it can be found that nano drug is with accurate quantity, relatively good targeting, specificity and absorbency. Necessary research of nano drug carriers can prevent and treat disease to a certain extent. CONCLUSION: Preparation of functionalized nanocarrier is simple and convenient, which can improve frequency of use of nano preparation technology and provide better development space for medical use. Therefore, nanocarriers should be combined with drugs with relatively strong specificity in clinics, in order to be able to conduct effective research on nanometer intelligent drug, effectively promote long-term development of nano biotechnology, and then provide favorable, reliable basis for clinical diagnosis and treatment. PMID- 27275112 TI - Forgotten topological index of chemical structure in drugs. AB - A massive of early drug tests implies that there exist strong inner relationships between the bio-medical and pharmacology characteristics of drugs and their molecular structures. The forgotten topological index was defined to be used in the analysis of drug molecular structures, which is quite helpful for pharmaceutical and medical scientists to grasp the biological and chemical characteristics of new drugs. Such tricks are popularly employed in developing countries where enough money is lacked to afford the relevant chemical reagents and equipment. In our article, by means of drug molecular structure analysis and edge dividing technology, we present the forgotten topological index of several widely used chemical structures which often appear in drug molecular graphs. PMID- 27275113 TI - Diagnosis of Genus Helicobacter through a hemi-nested PCR assay of 16S rRNA. AB - The present study aimed to establish a genus-specific PCR-based assay to detect helicobacters using 16S rRNA gene as the target template. We designed the hemi nested primers based on sequences of 16S rRNA gene of 34 types of Helicobacter species. The inclusivity, sensitivity, and specificity of the PCR assay using these primers were examined in three different models, comprising feces simulated samples, BLAB/c mice infection model and clinic patients samples. The detection sensitivity of Helicobacter pylori, Helicobacter hepaticus and Helicobacter bilis strains from feces simulated samples was all 102 CFU/ml. We successfully detected H. hepaticus and H. bilis in the liver, cecum and feces of experimentally infected mice. H. pylori was successfully detected in the feces samples from 3 patients infected with H. pylori while not in the feces samples from 3 healthy human. However, the C97/C05-C97/C98 PCR assay detected H. pylori in the 2 positive samples. Due to the PCR assay's excellent inclusivity, high sensitivity and specificity it may be used to detect the presence of Helicobacters. PMID- 27275114 TI - Endophytic filamentous fungi from a Catharanthus roseus: Identification and its hydrolytic enzymes. AB - This paper reported on the various filamentous fungi strains that were isolated from a wild grown Catharanthus roseus. Based on the morphological characteristics and molecular technique through a Polymerase Chain Reaction and DNA sequencing method using internal transcribed spacer (ITS), these fungi had been identified as a Colletotrichum sp., Macrophomina phaseolina, Nigrospora sphaerica and Fusarium solani. The ultrastructures of spores and hyphae were observed under a Scanning Electron Microscope. The hydrolytic enzyme test showed that all strains were positive in secreting cellulase. Colletotrichum sp. and F. solani strains also gave a positive result for amylase while only F. solani was capable to secrete protease. These fungi were putatively classified as endophytic fungi since they produced extracellular enzymes that allow them to penetrate plant cell walls and colonize with symbiotic properties. PMID- 27275115 TI - New discovery of cryptorchidism: Decreased retinoic acid in testicle. AB - This study focuses on investigation of cryptorchidism induced by flutamide (Flu) and its histopathological damage, and detects retinoic acid concentration in testicle tissue, in order to find a new method for clinical treatment to infertility caused by cryptorchidism. Twenty SD (Sprague Dawley) pregnant rats were randomly divided into Flu cryptorchidism group (n = 10) and normal control group (n = 10). HE stained for observing morphological difference. Transmission electron microscope (TEM) was used for observing the tight junction structure between Sertoli cells. Epididymal caudal sperms were counted and observed in morphology. The expression of stimulated by retinoic acid gene 8 (Stra8) was detected using immunohistochemistry, western blot, and Q-PCR. High performance liquid chromatography (HPLC) analysis was made on retinoic acid content. Sperm count and morphology observation confirmed cryptorchidism group was lower than normal group in sperm quantity and quality. The observation by TEM showed a loose structure of tight junctions between Sertoli cells. Immunohistochemistry, western blot, and Q-PCR showed that cryptorchidism group was significantly lower than normal group in the expression of Stra8. HPLC showed that retinoic acid content was significantly lower in cryptorchid testis than in normal testis. In the cryptorchidism model, retinoic acid content in testicular tissue has a significant reduction; testicles have significant pathological changes; damage exists in the structure of tight junctions between Sertoli cells; Stra8 expression has a significant reduction, perhaps mainly contributing to spermatogenesis disorder. PMID- 27275116 TI - The transport mechanism of monocarboxylate transporter on spinosin in Caco-2 cells. AB - OBJECTIVES: The aim of this study was to determine the uptake mechanism of spinosin (SPI) by the monocarboxylic acid transporters (MCTs) in Caco-2 cells. METHODS: The Caco-2 cells were pretreated with various monocarboxylic acids, and the uptake of spinosin from Caco-2 cells was measured by High Performance Liquid Chromatography (HPLC). KEY FINDINGS: Preloading of various monocarboxylic acids enhanced the uptake of SPI, especially salicylic acid (a substrate of MCTs) had a 23.4 times increase in SPI uptake, indicating that the monocarboxylic acid transporters had an efflux effect on SPI uptake and salicylic acid had a strong inhibition on SPI efflux in Caco-2 cells. At the same time, the uptake of SPI through Caco-2 cells was Na(+)- and temperature-dependent, pretreatment without Na(+) significantly increased the uptake of SPI by 1.85 times and incubated at low temperature (4 degrees C) SPI uptake increased 20% than that of 37 degrees C. Furthermore, SPI was transported mainly via a carrier-mediated transport: [Vmax = 5.364 MUg/mg protein, Km = 657.0 MUg/mL]. CONCLUSION: The uptake of spinosin (SPI) in Caco-2 cells was mainly regulated by the monocarboxylic acid transporters along with Salicylic acid. PMID- 27275117 TI - The effect of chitooligosaccharides on oleic acid-induced lipid accumulation in HepG2 cells. AB - This experiment aimed to evaluate the capacities of two types of chitooligosaccharides (COS) with different molecular weights for the ability to eliminate lipid accumulation in hepatocytes. We have established a lipid accumulation model in HepG2 cells for these studies in vitro, which was established by induction with oleic acid. The capacity of COS to eliminate lipid accumulation was evaluated using three metrics: the thiazolyl blue dye absorbance (MTT value), the morphology of intracellular lipid droplets and the triglyceride level (TG). Two types of COS with different molecular weights (1000 Da and 3000 Da) can significantly reduce intracellular lipid accumulation and decrease TG content in HepG2 cells, in a dose-dependent fashion. We found that low molecular weight COS is more efficacious than high molecular weight COS. Two types of COS can eliminate lipid accumulation induced by oleic acid in HepG2 cells, leading to an obvious hypolipidemic effect in vitro. These results suggest that COS may be effective preventive agents in fatty liver disease. PMID- 27275118 TI - Patients treatment with neuroglioma by teniposide and semustine and its influence on Twist and E-cadherin expression. AB - This study focuses on curative effects of teniposide combining with semustine on patients with neuroglioma and the influences on the expression of Twist and E cadherin in tissue. Sixty-eight patients with neuroglioma taking operation in our hospital were divided into two groups randomly. Single radiotherapy was given to 34 patients in group A, and teniposide (VM-26) and semustine (Me-CCUN) were added to radiotherapy for 34 patients in group B. Then, curative effects, survival rate, living quality and adverse reaction rate after operation were compared between two groups. Moreover, the difference in positive expression rate of Twist and E-cadherin before and after treatment between two groups was analyzed by immunohistochemistry. RESULTS: In group B, the effective rate of treatment was 88.2%, and the disease control rate was 70.6%, higher than 52.9% and 32.4% in group A with statistical significance (P < 0.05). Moreover, the survival rate in three years of group B was 44.1%, and the score of living quality was 67.11 +/- 4.32, and also higher than 23.5% and 63.79 +/- 4.53 in group A with statistical significance (P < 0.05). However, the difference between two groups in adverse reaction rate has no statistical significance (P > 0.05). In addition, the difference in positive expression rate of Twist and E-cadherin between group A and group B has no statistical significance before treatment (P > 0.05). After treatment, however, the positive rate of Twist in group B is lower than that in group A, while the positive rate of E-cadherin is higher. Both differences have statistical significance (P < 0.05). Chemotherapy of VM-26 combining with Me-CCNU can inhibit Twist expression and improve the expression rate of E-cadherin to help improving the curative effects and living quality and increasing survival rate. PMID- 27275119 TI - Biomechanical analysis of press-extension technique on degenerative lumbar with disc herniation and staggered facet joint. AB - This study investigates the effect of a new Chinese massage technique named "press-extension" on degenerative lumbar with disc herniation and facet joint dislocation, and provides a biomechanical explanation of this massage technique. Self-developed biomechanical software was used to establish a normal L1-S1 lumbar 3D FE model, which integrated the spine CT and MRI data-based anatomical structure. Then graphic technique is utilized to build a degenerative lumbar FE model with disc herniation and facet joint dislocation. According to the actual press-extension experiments, mechanic parameters are collected to set boundary condition for FE analysis. The result demonstrated that press-extension techniques bring the annuli fibrosi obvious induction effect, making the central nucleus pulposus forward close, increasing the pressure in front part. Study concludes that finite element modelling for lumbar spine is suitable for the analysis of press-extension technique impact on lumbar intervertebral disc biomechanics, to provide the basis for the disease mechanism of intervertebral disc herniation using press-extension technique. PMID- 27275120 TI - Structure characteristics of self-bonding boards during hot press for leukemia inhibition. AB - 80% leukemia was caused by indoor formaldehyde pollution. And the results have shown that the absorbances of many connection bonds (such as C-O-C, and C-OOC) increased. It could be inferred that a lot of bonds were produced and played the role of molecular crosslinking. After hot press, the content of lignin in Eucalyptus wood fiber was all lower than the ones of self-bonding boards. And the change of content of lignin was closely related to time and temperature of hot press. PMID- 27275121 TI - Research on AIDS patients' survival time after highly active antiretroviral therapy, treatment effect and treatment modes. AB - To fully define clinical efficacy of highly active antiretroviral therapy for AIDS, analyze patients' survival time and treatment mode after receiving treatment, and provide scientific theory to guide improvement of antiviral therapy, this paper selected 3100 cases of patients diagnosed with AIDS during April 2006 and April 2014 as object of this study. All patients were treated with highly active antiretroviral therapy. The main analysis contents of this study include CD4 + T lymphocyte count, viral load changes, incidence of opportunistic infections, specific cause of death and the like. The results show that patients' CD4 + T lymphocyte levels are significantly increased 3, 18, and 24 months after treatment, difference between the situation after and before receiving treatment, P < 0.05, with statistically significant difference. Analyzed from effective inhibition of virus, effective inhibition rate is 72.58.0% (2250/3100). Main causes of death in patients is usually respiratory failure. It thus can be concluded that highly active antiretroviral therapy for AIDS is with good clinical effect, which can effectively improve survival time of patients. So it enjoys application value of being widely used in clinical treatment of AIDS. PMID- 27275122 TI - Effect of cynomorium flavonoids on morphology of perimenopausal depression mice model. AB - OBJECTIVE: In this report, the effects of cynomorium flavonoids on mouse model of perimenopausal depression were investigated. METHOD: 60 ovariectomized female mice were randomly divided into 6 groups evenly: high, medium and low doses of cynomorium flavonoids groups (400 mg kg(-1), 200 mg kg(-1), 100 mg kg(-1)), Gengnian'an capsule group (675 mg kg(-1)), soy isoflavones soft capsule group (250 mg kg(-1)), and model group. Give the corresponding drug five days after surgery once a day, consecutive thirty days. The model group and control group were given the water of same volume. The model related groups were applied with different stress for consecutive eighteen days. Kill the mice and remove the thymus, spleen, uterus and one hand of brain when it is 2 h after the last administration in mice of each group. Observe the histological changes of each group under light microscope. RESULTS: By observing the pathological section, compared with model group, the pathological changes of the uterus and hypothalamus of mice were significantly improved. The thymic cortex markedly thickened, volume of splenic nodule also significantly increased, and the number of lymphocytes significantly increased (p < 0.01). Simulation results show that the high dose of cynomorium flavonoids group has the best effective. CONCLUSION: Cynomorium flavonoids on mouse uterus, hypothalamus, thymus and spleen lesions have a significant role in the improvement. Cynomorium flavonoids have a good therapeutic effect on mice with perimenopausal depression. PMID- 27275123 TI - Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells. AB - To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice. PMID- 27275124 TI - Serum TNF-alpha, GTH and MDA of high-fat diet-induced obesity and obesity resistant rats. AB - OBJECTIVE: Mechanism of high fat diet-induced obesity is analyzed and serum tumor necrosis factor, malondialdehyde and glutathione levels of obesity resistant rats are effectively analyzed. METHODS: 120 male SD rats were grouped into obesity group and control group, each group with 60 rats. Obese rats were fed with high fat diet, while control rats were fed with ordinary fodder. After six months of feeding, growth degree of two groups of rats is observed , and the rats are divided into obesity group and obesity resistant group based on extent of growth. Then glutathione, tumor necrosis factor-alpha and MDA content in bat serum are detected with enzyme-linked immunosorbent assay. RESULTS: The content of tumor necrosis factor alpha in obese rats and obesity resistant rats is far higher than that in control group (P < 0.05), there exists no statistical significance (P > 0.05) in tumor necrosis factor alpha in obesity group and obesity resistant group, glutathione level of obesity group rats and obesity resistant group rats is significantly increased (P < 0.05) compared with that of control group, and also serum MDA level of the two groups has statistical significance compared with that of normal control group (P < 0.05). CONCLUSION: Among rats fed with high fat diet, in comparison with weight of obesity resistant rats and control group rats, there is no statistically significant difference, (P > 0.05). However, high fat diet will impact mechanisms in vivo in rats, which then induces oxidative stress response and inflammatory response in rats. PMID- 27275125 TI - Pathogen distribution and drug resistance of nephrology patients with urinary tract infections. AB - OBJECTIVE: Pathogen distribution characteristics of nephrology patients with urinary tract infections are studied, and drug resistance of nephrology and urinary tract infection disease are analyzed, so as to provide sufficient evidence for treatment of patients. METHODS: Conduct randomized control study of 3500 cases of nephrology patients with urinary tract infections treated in different hospitals from December 2013 to December 2015, isolate pathogens in patients' urine samples, perform identification and drug sensitive test and then conduct detailed analysis of drug resistance of pathogens. RESULTS: Through isolation of pathogens, it can be found that all pathogens include Escherichia coli, Gram-positive cocci, gram-negative bacteria, fungi, Acinetobacter baumannii, Enterococcus faecalis, and urinary Enterococcus. Among them, proportion of E. coli is the largest. Patients have relatively high drug resistance to ceftriaxone, gentamicin, ciprofloxacin and cotrimoxazole. CONCLUSION: For nephrology patients with urinary tract infection, the main pathogen is E. coli, which has had some drug resistance. Drug resistance detection of pathogen should be strengthened in clinics, so as to provide strong guidance for clinical treatment and promote effective treatment of patients. PMID- 27275126 TI - Protective effect of Astragaloside IV against sepsis-induced acute lung injury in rats. AB - The study aimed to explore the protective effects of AS-IV against sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) method in Sprague Dawley rats. Rats were randomly assigned into five groups: animals undergoing a sham CLP (sham group); animals undergoing CLP (CLP group); animals undergoing CLP and treated with AS-IV at 2.5 mg/kg bw (low-dose AS-IV [L-AS] group), at 5 mg/kg bw (mid-dose AS-IV [M-AS] group), and at 10 mg/kg bw (high-dose AS-IV [H-AS] group). At 6 h, 12 h and 24 h post-CLP surgery, six rats were respectively sacrificed to collect blood and lung tissue samples. The levels of arterial blood gas index, lung water content, protein level and leukocyte counts (total amount, neutrophils and lymphocytes) in bronchoalveolar lavage fluid (BALF) and cytokines such as TNF-alpha and IL-6 in BALF were measured at each time point in different groups. HE-staining and optical microscopy were performed to examine the pathological changes in lungs. The 72 h-survival rate of each group was also recorded. PaO2 was decreased significantly, while the lung water content, BALF protein level, cell numbers, BALF cytokine TNF-alpha and IL-6 levels were increased significantly for CLP group as compared with sham group. Moreover, pathological injury was observed in lung tissue indicating the successful sepsis induced ALI model. Speaking of the effect of AS-IV, we founded that, compared with the CLP group, the AS-IV treatment groups could significantly alleviate all the above negative changes exited in the CLP group in a dose-dependent manner. What's more, the pathological injury was also gradually improved by AS-IV treatment compared with the CLP rats. AS-IV exerts its protective effect against sepsis-induced ALI in rats via improving pulmonary ventilation function, decreasing the permeability of alveolar epithelium and capillary as well as repressing lung inflammation. PMID- 27275127 TI - Analgesic effect and possible mechanism of SCH772984 intrathecal injection on rats with bone cancer pain. AB - This study is to establish a model of rat tibial osteocarcinoma pain, intrathecally inject specific ERK1/2 inhibitors SCH772984, observe the analgesic effect, and discuss the influence of ERK-P90RSK-Fos signal path in bone cancer pain. Forty female SD rats were randomly divided into 5 groups. Establish a bone cancer pain model after putting the intrathecal tube 5d and determine the rats' mechanical withdrawal threshold (MWT) after tube 5d; 40 SD rats with intrathecal tube back 5d were randomly divided into 5 groups. Sham Group receives no medication, the other four respectively receive 5% DMSO 10 MUl, SCH 0.1, 1.0, 10 MUg (SCH dissolved in 10 MUl 5% DMSO) intrathecally. Determine the rats' mechanical withdrawal threshold (MWT) before and after giving medication 1, 3, 6, 9, 12, 15, 18, 24 h, and 2 min spontaneous paw withdrawal. Western blot and immuno-fluorescence determine the expression condition of spinal cord dorsal horn of p-ERK, p-p90RSK and Fos protein. Intrathecal injection of SCH772984 has analgesic effects on rats with bone cancer pain, and the effects enhance with increasing dose; intrathecal injection of SCH772984 10 MUg could greatly reduce the expression of spinal dorsal horn Fos protein. Injecting walker 256 tumor cells into rats' tibia could cause behavior changes, such as idiopathic pain sensitivity and pain; the intrathecal tube almost has no effect on motor function of rats; ERK1/2 is involved in bone cancer pain, and intrathecal injection of ERK1/2 specific inhibitors SCH772984 10 MUg may effectively relieve bone cancer pain. PMID- 27275128 TI - Preparation and evaluation of rotigotine-loaded implant for the treatment of Parkinson's disease and its evolution study. AB - PURPOSE: To develop rotigotine-loaded implants (RI) to achieve continuous release of rotigotine for long duration for the treatment of Parkinson's disease (PD). METHODS: RI was prepared by hot-melt extrusion method using poly (lactide-co glycolide) (PLGA) as the matrix. In vitro drug release was optimized by drug loading, melting temperature during preparing process and additives. The surface and internal morphology of RI was imaged by SEM. The in vivo release profile of RI was investigated on rat. RESULTS: RI prepared with PLGA 7525 5A showed sustained release of 40 days while suffering a lag phase, which was significantly shortened by blending 5050 2A and mannitol in the matrix. RI prepared by 7525 5A/5050 2A/mannitol = 55:10:5 (rotigotine 30%) showed a 40-day sustained release in vivo with no lag phase. The drug release from RI was also affected by drug loading and melting temperature probably due to the drug state existed in the implant. The evolution of implants during release process was correlated well with the drug release kinetics. CONCLUSION: RI could achieve sustained drug release for 40 days which could supply an alternative of continuous dopaminergic stimulation (CDS) for the treatment of PD. PMID- 27275129 TI - The standard aqueous stem bark extract of Mangifera indica L. inhibits toxic PLA2 - NN-XIb-PLA2 of Indian cobra venom. AB - The aqueous extract of Mangifera indica is known to possess diverse medicinal properties, which also includes anti-snake venom activities. However, its inhibitory potency and mechanism of action on multi-toxic snake venom phospholipases A2s are still unknown. Therefore, the objective of this study was to evaluate the modulatory effect of standard aqueous bark extract of M. indica on NN-XIb-PLA2 of Indian cobra venom. The in vitro sPLA2, in situ hemolytic and in vivo edema inhibition effect were carried out as described. Also the effect of substrate and calcium concentration was carried out. M. indica extract dose dependently inhibited the GIA sPLA2 (NN-XIb-PLA2) activity with an IC50 value of 7.6 MUg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ~40 MUg/ml concentration. Further, M. indica extract (0-50 MUg/ml) inhibited the edema formed in a dose dependent manner. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect of M. indica extract on the NN-XIb-PLA2. Further, the inhibition was irreversible as evident from binding studies. The in vitro inhibition is well correlated with in situ and in vivo edema inhibiting activities of M. indica. As the inhibition is independent of substrate and calcium and was irreversible, it can be concluded that M. indica extract mode of inhibition could be due to direct interaction of components present in the extract with the PLA2 enzyme. The aqueous extract of M. indica effectively inhibits svPLA2 enzymatic and its associated toxic activities, which substantiate their anti-snake venom properties. Further in-depth studies on the role and mechanism of the principal constituents present in the extract, responsible for the anti-PLA2 activity will be interesting to develop them into potent antisnake component and also as an anti-inflammatory agent. PMID- 27275130 TI - Investigation of the Mechanism of Electron Capture and Electron Transfer Dissociation of Peptides with a Covalently Attached Free Radical Hydrogen Atom Scavenger. AB - The mechanisms of electron capture and electron transfer dissociation (ECD and ETD) are investigated by covalently attaching a free-radical hydrogen atom scavenger to a peptide. The 2,2,6,6-tetramethylpiperidin-l-oxyl (TEMPO) radical was chosen as the scavenger due to its high hydrogen atom affinity (ca. 280 kJ/mol) and low electron affinity (ca. 0.45 ev), and was derivatized to the model peptide, FQXTEMPOEEQQQTEDELQDK. The XTEMPO residue represents a cysteinyl residue derivatized with an acetamido-TEMPO group. The acetamide group without TEMPO was also examined as a control. The gas phase proton affinity (882 kJ/mol) of TEMPO is similar to backbone amide carbonyls (889 kJ/mol), minimizing perturbation to internal solvation and sites of protonation of the derivatized peptides. Collision induced dissociation (CID) of the TEMPO tagged peptide dication generated stable odd-electron b and y type ions without indication of any TEMPO radical induced fragmentation initiated by hydrogen abstraction. The type and abundance of fragment ions observed in the CID spectra of the TEMPO and acetamide tagged peptides are very similar. However, ECD of the TEMPO labeled peptide dication yielded no backbone cleavage. We propose that a labile hydrogen atom in the charge reduced radical ions is scavenged by the TEMPO radical moiety, resulting in inhibition of N-Calpha backbone cleavage processes. Supplemental activation after electron attachment (ETcaD) and CID of the charge-reduced precursor ion generated by electron transfer of the TEMPO tagged peptide dication produced a series of b + H (bH) and y + H (yH) ions along with some c ions having suppressed intensities, consistent with stable O-H bond formation at the TEMPO group. In summary, the results indicate that ECD and ETD backbone cleavage processes are inhibited by scavenging of a labile hydrogen atom by the localized TEMPO radical moiety. This observation supports the conjecture that ECD and ETD processes involve long-lived intermediates formed by electron capture/transfer in which a labile hydrogen atom is present and plays a key role with low energy processes leading to c and z ion formation. Ab initio and density functional calculations are performed to support our conclusion, which depends most importantly on the proton affinity, electron affinity and hydrogen atom affinity of the TEMPO moiety. PMID- 27275131 TI - How much training data for facial action unit detection? AB - By systematically varying the number of subjects and the number of frames per subject, we explored the influence of training set size on appearance and shape based approaches to facial action unit (AU) detection. Digital video and expert coding of spontaneous facial activity from 80 subjects (over 350,000 frames) were used to train and test support vector machine classifiers. Appearance features were shape-normalized SIFT descriptors and shape features were 66 facial landmarks. Ten-fold cross-validation was used in all evaluations. Number of subjects and number of frames per subject differentially affected appearance and shape-based classifiers. For appearance features, which are high-dimensional, increasing the number of training subjects from 8 to 64 incrementally improved performance, regardless of the number of frames taken from each subject (ranging from 450 through 3600). In contrast, for shape features, increases in the number of training subjects and frames were associated with mixed results. In summary, maximal performance was attained using appearance features from large numbers of subjects with as few as 450 frames per subject. These findings suggest that variation in the number of subjects rather than number of frames per subject yields most efficient performance. PMID- 27275132 TI - Accuracy in Rietveld quantitative phase analysis: a comparative study of strictly monochromatic Mo and Cu radiations. AB - This study reports 78 Rietveld quantitative phase analyses using Cu Kalpha1, Mo Kalpha1 and synchrotron radiations. Synchrotron powder diffraction has been used to validate the most challenging analyses. From the results for three series with increasing contents of an analyte (an inorganic crystalline phase, an organic crystalline phase and a glass), it is inferred that Rietveld analyses from high energy Mo Kalpha1 radiation have slightly better accuracies than those obtained from Cu Kalpha1 radiation. This behaviour has been established from the results of the calibration graphics obtained through the spiking method and also from Kullback-Leibler distance statistic studies. This outcome is explained, in spite of the lower diffraction power for Mo radiation when compared to Cu radiation, as arising because of the larger volume tested with Mo and also because higher energy allows one to record patterns with fewer systematic errors. The limit of detection (LoD) and limit of quantification (LoQ) have also been established for the studied series. For similar recording times, the LoDs in Cu patterns, ~0.2 wt%, are slightly lower than those derived from Mo patterns, ~0.3 wt%. The LoQ for a well crystallized inorganic phase using laboratory powder diffraction was established to be close to 0.10 wt% in stable fits with good precision. However, the accuracy of these analyses was poor with relative errors near to 100%. Only contents higher than 1.0 wt% yielded analyses with relative errors lower than 20%. PMID- 27275133 TI - In situ diagnostics of the crystal-growth process through neutron imaging: application to scintillators. AB - Neutrons are known to be unique probes in situations where other types of radiation fail to penetrate samples and their surrounding structures. In this paper it is demonstrated how thermal and cold neutron radiography can provide time-resolved imaging of materials while they are being processed (e.g. while growing single crystals). The processing equipment, in this case furnaces, and the scintillator materials are opaque to conventional X-ray interrogation techniques. The distribution of the europium activator within a BaBrCl:Eu scintillator (0.1 and 0.5% nominal doping concentrations per mole) is studied in situ during the melting and solidification processes with a temporal resolution of 5-7 s. The strong tendency of the Eu dopant to segregate during the solidification process is observed in repeated cycles, with Eu forming clusters on multiple length scales (only for clusters larger than ~50 um, as limited by the resolution of the present experiments). It is also demonstrated that the dopant concentration can be quantified even for very low concentration levels (~0.1%) in 10 mm thick samples. The interface between the solid and liquid phases can also be imaged, provided there is a sufficient change in concentration of one of the elements with a sufficient neutron attenuation cross section. Tomographic imaging of the BaBrCl:0.1%Eu sample reveals a strong correlation between crystal fractures and Eu-deficient clusters. The results of these experiments demonstrate the unique capabilities of neutron imaging for in situ diagnostics and the optimization of crystal-growth procedures. PMID- 27275134 TI - NearTree, a data structure and a software toolkit for the nearest-neighbor problem. AB - Many problems in crystallography and other fields can be treated as nearest neighbor problems. The neartree data structure provides a flexible way to organize and retrieve metric data. In some cases, it can provide near-optimal performance. NearTree is a software tool that constructs neartrees and provides a number of different query tools. PMID- 27275135 TI - Structure of nanocrystalline calcium silicate hydrates: insights from X-ray diffraction, synchrotron X-ray absorption and nuclear magnetic resonance. AB - The structure of nanocrystalline calcium silicate hydrates (C-S-H) having Ca/Si ratios ranging between 0.57 +/- 0.05 and 1.47 +/- 0.04 was studied using an electron probe micro-analyser, powder X-ray diffraction, 29Si magic angle spinning NMR, and Fourier-transform infrared and synchrotron X-ray absorption spectroscopies. All samples can be described as nanocrystalline and defective tobermorite. At low Ca/Si ratio, the Si chains are defect free and the Si Q3 and Q2 environments account, respectively, for up to 40.2 +/- 1.5% and 55.6 +/- 3.0% of the total Si, with part of the Q3 Si being attributable to remnants of the synthesis reactant. As the Ca/Si ratio increases up to 0.87 +/- 0.02, the Si Q3 environment decreases down to 0 and is preferentially replaced by the Q2 environment, which reaches 87.9 +/- 2.0%. At higher ratios, Q2 decreases down to 32.0 +/- 7.6% for Ca/Si = 1.38 +/- 0.03 and is replaced by the Q1 environment, which peaks at 68.1 +/- 3.8%. The combination of X-ray diffraction and NMR allowed capturing the depolymerization of Si chains as well as a two-step variation in the layer-to-layer distance. This latter first increases from ~11.3 A (for samples having a Ca/Si ratio <~0.6) up to 12.25 A at Ca/Si = 0.87 +/- 0.02, probably as a result of a weaker layer-to-layer connectivity, and then decreases down to 11 A when the Ca/Si ratio reaches 1.38 +/- 0.03. The decrease in layer-to-layer distance results from the incorporation of interlayer Ca that may form a Ca(OH)2-like structure, nanocrystalline and intermixed with C-S-H layers, at high Ca/Si ratios. PMID- 27275136 TI - X-ray diffraction from nonuniformly stretched helical molecules. AB - The fibrous proteins in living cells are exposed to mechanical forces interacting with other subcellular structures. X-ray fiber diffraction is often used to assess deformation and movement of these proteins, but the analysis has been limited to the theory for fibrous molecular systems that exhibit helical symmetry. However, this approach cannot adequately interpret X-ray data from fibrous protein assemblies where the local strain varies along the fiber length owing to interactions of its molecular constituents with their binding partners. To resolve this problem a theoretical formulism has been developed for predicting the diffraction from individual helical molecular structures nonuniformly strained along their lengths. This represents a critical first step towards modeling complex dynamical systems consisting of multiple helical structures using spatially explicit, multi-scale Monte Carlo simulations where predictions are compared with experimental data in a 'forward' process to iteratively generate ever more realistic models. Here the effects of nonuniform strains and the helix length on the resulting magnitude and phase of diffraction patterns are quantitatively assessed. Examples of the predicted diffraction patterns of nonuniformly deformed double-stranded DNA and actin filaments in contracting muscle are presented to demonstrate the feasibly of this theoretical approach. PMID- 27275137 TI - A crystallization apparatus for temperature-controlled flow-cell dialysis with real-time visualization. AB - Many instrumentation developments in crystallization have concentrated on massive parallelization assays and reduction of sample volume per experiment to find initial crystallization conditions. Yet improving the size and diffraction quality of the crystals for diffraction studies often requires decoupling of crystal nucleation and growth. This in turn requires the control of variables such as precipitant and protein concentration, equilibration rate, and temperature, which are all difficult parameters to control in the existing setups. The success of the temperature-controlled batch method, originally developed to grow very large crystals for neutron crystallography, demonstrated that the rational optimization of crystal growth has potential in structural biology. A temperature-controlled dialysis button has been developed for our previous device, and a prototype of an integrated apparatus for the rational optimization of crystal growth by mapping and manipulating temperature precipitant concentration phase diagrams has been constructed. The presented approach differs from the current paradigm, since it involves serial instead of parallel experiments, exploring multiple crystallization conditions with the same protein sample. The sample is not consumed in the experiment and the conditions can be changed in a reversible fashion, using dialysis with a flowing precipitant reservoir as well as precise temperature control. The control software allows visualization of the crystals, as well as control of the temperature and composition of the crystallization solution. The rational crystallization optimization strategies presented here allow tailoring of crystal size, morphology and diffraction quality, significantly reducing the time, effort and amount of expensive protein material required for structure determination. PMID- 27275138 TI - Quantifying radiation damage in biomolecular small-angle X-ray scattering. AB - Small-angle X-ray scattering (SAXS) is an increasingly popular technique that provides low-resolution structural information about biological macromolecules in solution. Many of the practical limitations of the technique, such as minimum required sample volume, and of experimental design, such as sample flow cells, are necessary because the biological samples are sensitive to damage from the X rays. Radiation damage typically manifests as aggregation of the sample, which makes the collected data unreliable. However, there has been little systematic investigation of the most effective methods to reduce damage rates, and results from previous damage studies are not easily compared with results from other beamlines. Here a methodology is provided for quantifying radiation damage in SAXS to provide consistent results between different experiments, experimenters and beamlines. These methods are demonstrated on radiation damage data collected from lysozyme, glucose isomerase and xylanase, and it is found that no single metric is sufficient to describe radiation damage in SAXS for all samples. The radius of gyration, molecular weight and integrated SAXS profile intensity constitute a minimal set of parameters that capture all types of observed behavior. Radiation sensitivities derived from these parameters show a large protein dependence, varying by up to six orders of magnitude between the different proteins tested. This work should enable consistent reporting of radiation damage effects, allowing more systematic studies of the most effective minimization strategies. PMID- 27275139 TI - Neutron and hard X-ray diffraction studies of the isothermal transformation kinetics in the research reactor fuel candidate U-8 wt%Mo. AB - Exposing uranium-molybdenum alloys (UMo) retained in the gamma phase to elevated temperatures leads to transformation reactions during which the gamma-UMo phase decomposes into the thermal equilibrium phases, i.e. U2Mo and alpha-U. Since alpha-U is not suitable for a nuclear fuel exposed to high burn-up, it is necessary to retain the gamma-UMo phase during the production process of the fuel elements for modern high-performance research reactors. The present work deals with the isothermal transformation kinetics in U-8 wt%Mo alloys for temperatures between 673 and 798 K and annealing durations of up to 48 h. Annealed samples were examined at room temperature using either X-ray or neutron diffraction to determine the phase composition after thermal treatment, and in situ annealing studies disclosed the onset of phase decomposition. While for temperatures of 698 and 673 K the start of decomposition is delayed, for higher temperatures the first signs of transformation are already observable within 3 h of annealing. The typical C-shaped curves in a time-temperature-transformation (TTT) diagram for both the start and the end of phase decomposition could be determined in the observed temperature regime. Therefore, a revised TTT diagram for U-8 wt%Mo between 673 and 798 K and annealing durations of up to 48 h is proposed. PMID- 27275140 TI - Ultra-small-angle neutron scattering with azimuthal asymmetry. AB - Small-angle neutron scattering (SANS) measurements from thin sections of rock samples such as shales demand as great a scattering vector range as possible because the pores cover a wide range of sizes. The limitation of the scattering vector range for pinhole SANS requires slit-smeared ultra-SANS (USANS) measurements that need to be converted to pinhole geometry. The desmearing algorithm is only successful for azimuthally symmetric data. Scattering from samples cut parallel to the plane of bedding is symmetric, exhibiting circular contours on a two-dimensional detector. Samples cut perpendicular to the bedding show elliptically dependent contours with the long axis corresponding to the normal to the bedding plane. A method is given for converting such asymmetric data collected on a double-crystal diffractometer for concatenation with the usual pinhole-geometry SANS data. The aspect ratio from the SANS data is used to modify the slit-smeared USANS data to produce quasi-symmetric contours. Rotation of the sample about the incident beam may result in symmetric data but cannot extract the same information as obtained from pinhole geometry. PMID- 27275141 TI - Fast two-dimensional grid and transmission X-ray microscopy scanning methods for visualizing and characterizing protein crystals. AB - A fast continuous grid scan protocol has been incorporated into the Swiss Light Source (SLS) data acquisition and analysis software suite on the macromolecular crystallography (MX) beamlines. Its combination with fast readout single-photon counting hybrid pixel array detectors (PILATUS and EIGER) allows for diffraction based identification of crystal diffraction hotspots and the location and centering of membrane protein microcrystals in the lipid cubic phase (LCP) in in meso in situ serial crystallography plates and silicon nitride supports. Diffraction-based continuous grid scans with both still and oscillation images are supported. Examples that include a grid scan of a large (50 nl) LCP bolus and analysis of the resulting diffraction images are presented. Scanning transmission X-ray microscopy (STXM) complements and benefits from fast grid scanning. STXM has been demonstrated at the SLS beamline X06SA for near-zero-dose detection of protein crystals mounted on different types of sample supports at room and cryogenic temperatures. Flash-cooled crystals in nylon loops were successfully identified in differential and integrated phase images. Crystals of just 10 um thickness were visible in integrated phase images using data collected with the EIGER detector. STXM offers a truly low-dose method for locating crystals on solid supports prior to diffraction data collection at both synchrotron microfocusing and free-electron laser X-ray facilities. PMID- 27275142 TI - Rapid automated superposition of shapes and macromolecular models using spherical harmonics. AB - A rapid algorithm to superimpose macromolecular models in Fourier space is proposed and implemented (SUPALM). The method uses a normalized integrated cross term of the scattering amplitudes as a proximity measure between two three dimensional objects. The reciprocal-space algorithm allows for direct matching of heterogeneous objects including high- and low-resolution models represented by atomic coordinates, beads or dummy residue chains as well as electron microscopy density maps and inhomogeneous multi-phase models (e.g. of protein-nucleic acid complexes). Using spherical harmonics for the computation of the amplitudes, the method is up to an order of magnitude faster than the real-space algorithm implemented in SUPCOMB by Kozin & Svergun [J. Appl. Cryst. (2001 ?), 34, 33-41]. The utility of the new method is demonstrated in a number of test cases and compared with the results of SUPCOMB. The spherical harmonics algorithm is best suited for low-resolution shape models, e.g. those provided by solution scattering experiments, but also facilitates a rapid cross-validation against structural models obtained by other methods. PMID- 27275144 TI - Identification of rogue datasets in serial crystallography. AB - Advances in beamline optics, detectors and X-ray sources allow new techniques of crystallographic data collection. In serial crystallography, a large number of partial datasets from crystals of small volume are measured. Merging of datasets from different crystals in order to enhance data completeness and accuracy is only valid if the crystals are isomorphous, i.e. sufficiently similar in cell parameters, unit-cell contents and molecular structure. Identification and exclusion of non-isomorphous datasets is therefore indispensable and must be done by means of suitable indicators. To identify rogue datasets, the influence of each dataset on CC1/2 [Karplus & Diederichs (2012 ?). Science, 336, 1030-1033], the correlation coefficient between pairs of intensities averaged in two randomly assigned subsets of observations, is evaluated. The presented method employs a precise calculation of CC1/2 that avoids the random assignment, and instead of using an overall CC1/2, an average over resolution shells is employed to obtain sensible results. The selection procedure was verified by measuring the correlation of observed (merged) intensities and intensities calculated from a model. It is found that inclusion and merging of non-isomorphous datasets may bias the refined model towards those datasets, and measures to reduce this effect are suggested. PMID- 27275145 TI - Modeling truncated pixel values of faint reflections in MicroED images. AB - The weak pixel counts surrounding the Bragg spots in a diffraction image are important for establishing a model of the background underneath the peak and estimating the reliability of the integrated intensities. Under certain circumstances, particularly with equipment not optimized for low-intensity measurements, these pixel values may be corrupted by corrections applied to the raw image. This can lead to truncation of low pixel counts, resulting in anomalies in the integrated Bragg intensities, such as systematically higher signal-to-noise ratios. A correction for this effect can be approximated by a three-parameter lognormal distribution fitted to the weakly positive-valued pixels at similar scattering angles. The procedure is validated by the improved refinement of an atomic model against structure factor amplitudes derived from corrected micro-electron diffraction (MicroED) images. PMID- 27275143 TI - Room-temperature macromolecular crystallography using a micro-patterned silicon chip with minimal background scattering. AB - Recent success at X-ray free-electron lasers has led to serial crystallography experiments staging a comeback at synchrotron sources as well. With crystal lifetimes typically in the millisecond range and the latest-generation detector technologies with high framing rates up to 1 kHz, fast sample exchange has become the bottleneck for such experiments. A micro-patterned chip has been developed from single-crystalline silicon, which acts as a sample holder for up to several thousand microcrystals at a very low background level. The crystals can be easily loaded onto the chip and excess mother liquor can be efficiently removed. Dehydration of the crystals is prevented by keeping them in a stream of humidified air during data collection. Further sealing of the sample holder, for example with Kapton, is not required. Room-temperature data collection from insulin crystals loaded onto the chip proves the applicability of the chip for macromolecular crystallography. Subsequent structure refinements reveal no radiation-damage-induced structural changes for insulin crystals up to a dose of 565.6 kGy, even though the total diffraction power of the crystals has on average decreased to 19.1% of its initial value for the same dose. A decay of the diffracting power by half is observed for a dose of D1/2 = 147.5 +/- 19.1 kGy, which is about 1/300 of the dose before crystals show a similar decay at cryogenic temperatures. PMID- 27275146 TI - Data processing pipeline for serial femtosecond crystallography at SACLA. AB - A data processing pipeline for serial femtosecond crystallography at SACLA was developed, based on Cheetah [Barty et al. (2014). J. Appl. Cryst.47, 1118-1131] and CrystFEL [White et al. (2016). J. Appl. Cryst.49, 680-689]. The original programs were adapted for data acquisition through the SACLA API, thread and inter-node parallelization, and efficient image handling. The pipeline consists of two stages: The first, online stage can analyse all images in real time, with a latency of less than a few seconds, to provide feedback on hit rate and detector saturation. The second, offline stage converts hit images into HDF5 files and runs CrystFEL for indexing and integration. The size of the filtered compressed output is comparable to that of a synchrotron data set. The pipeline enables real-time feedback and rapid structure solution during beamtime. PMID- 27275147 TI - Hummingbird: monitoring and analyzing flash X-ray imaging experiments in real time. AB - Advances in X-ray detectors and increases in the brightness of X-ray sources combined with more efficient sample delivery techniques have brought about tremendous increases in the speed of data collection in diffraction experiments. Using X-ray free-electron lasers such as the Linac Coherent Light Source (LCLS), more than 100 diffraction patterns can be collected in a second. These high data rates are invaluable for flash X-ray imaging (FXI), where aerosolized samples are exposed to the X-ray beam and the resulting diffraction patterns are used to reconstruct a three-dimensional image of the sample. Such experiments require immediate feedback on the quality of the data collected to adjust or validate experimental parameters, such as aerosol injector settings, beamline geometry or sample composition. The scarcity of available beamtime at the laser facilities makes any delay extremely costly. This paper presents Hummingbird, an open-source scalable Python-based software tool for real-time analysis of diffraction data with the purpose of giving users immediate feedback during their experiments. Hummingbird provides a fast, flexible and easy-to-use framework. It has already proven to be of great value in numerous FXI experiments at the LCLS. PMID- 27275148 TI - IOTA: integration optimization, triage and analysis tool for the processing of XFEL diffraction images. AB - Serial femtosecond crystallography (SFX) uses an X-ray free-electron laser to extract diffraction data from crystals not amenable to conventional X-ray light sources owing to their small size or radiation sensitivity. However, a limitation of SFX is the high variability of the diffraction images that are obtained. As a result, it is often difficult to determine optimal indexing and integration parameters for the individual diffraction images. Presented here is a software package, called IOTA, which uses a grid-search technique to determine optimal spot-finding parameters that can in turn affect the success of indexing and the quality of integration on an image-by-image basis. Integration results can be filtered using a priori information about the Bravais lattice and unit-cell dimensions and analyzed for unit-cell isomorphism, facilitating an improvement in subsequent data-processing steps. PMID- 27275149 TI - On the release of cppxfel for processing X-ray free-electron laser images. AB - As serial femtosecond crystallography expands towards a variety of delivery methods, including chip-based methods, and smaller collected data sets, the requirement to optimize the data analysis to produce maximum structure quality is becoming increasingly pressing. Here cppxfel, a software package primarily written in C++, which showcases several data analysis techniques, is released. This software package presently indexes images using DIALS (diffraction integration for advanced light sources) and performs an initial orientation matrix refinement, followed by post-refinement of individual images against a reference data set. Cppxfel is released with the hope that the unique and useful elements of this package can be repurposed for existing software packages. However, as released, it produces high-quality crystal structures and is therefore likely to be also useful to experienced users of X-ray free-electron laser (XFEL) software who wish to maximize the information extracted from a limited number of XFEL images. PMID- 27275150 TI - OnDA: online data analysis and feedback for serial X-ray imaging. AB - This article describes a free and open-source data analysis utility designed for fast online feedback during serial X-ray diffraction and scattering experiments: OnDA (online data analysis). Three complete real-time monitors for common types of serial X-ray imaging experiments are presented. These monitors are capable of providing the essential information required for quick decision making in the face of extreme rates of data collection. In addition, a set of modules, functions and algorithms that allow developers to modify the provided monitors or develop new ones are provided. The emphasis here is on simple, modular and scalable code that is based on open-source libraries and protocols. OnDA monitors have already proven to be invaluable tools in several experiments, especially for scoring and monitoring of diffraction data during serial crystallography experiments at both free-electron laser and synchrotron facilities. It is felt that in the future the kind of fast feedback that OnDA monitors provide will help researchers to deal with the expected very high throughput data flow at next generation facilities such as the European X-ray free-electron laser. PMID- 27275151 TI - DCC: a Swiss army knife for structure factor analysis and validation. AB - Since 2008, X-ray structure depositions to the Protein Data Bank archive (PDB) have required submission of experimental data in the form of structure factor files. RCSB PDB has developed the program DCC to allow worldwide PDB (wwPDB; http://wwpdb.org) biocurators, using a single command-line program, to invoke a number of third-party software packages to compare the model file with the experimental data. DCC functionality includes structure factor validation, electron-density map generation and slicing, local electron-density analysis, and residual B factor analysis. DCC outputs a summary containing various crystallographic statistics in PDBx/mmCIF format for use in automatic data processing and archiving pipelines. PMID- 27275152 TI - Retraction: Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design. AB - [This retracts the article on p. 137 in vol. 5, PMID: 24966835.]. PMID- 27275153 TI - Determinants of Mortality in Patients with Chronic Kidney Disease Undergoing Percutaneous Coronary Intervention. AB - BACKGROUND: Renal impairment is a known predictor of mortality in both the general population and in patients with cardiac disease. The aim of this study was to evaluate factors that determine mortality in patients with chronic kidney disease (CKD) who have undergone percutaneous coronary intervention (PCI). METHODS: In this study we included 293 consecutive patients with CKD who underwent PCI between 1st January 2007 and 30th September 2012. The primary outcome that we studied was all-cause mortality in a follow-up period of 12-69 months (mean 38.8 +/- 21.7). RESULTS: Age (p < 0.001), PCI indication (p = 0.035), CKD stage (p < 0.001) and left ventricular ejection fraction (p < 0.001) were significantly related to mortality. CKD stage 5 [hazard ratio (HR) = 6.39, 95% CI: 1.51-27.12) and severely impaired left ventricular function (HR = 4.04, 95% CI: 2.15-7.59) were the strongest predictors of mortality. Other factors tested (gender, hypertension, diabetes, hyperlipidaemia, established peripheral vascular disease/stroke, coronary arteries intervened, number of vessels treated, number of stents implanted and length of lesion treated) did not show any correlation with mortality. CONCLUSIONS: The mortality of patients with CKD undergoing PCI increases with age, worsening CKD stage and deteriorating left ventricular systolic function, and it is also higher in patients with acute coronary syndromes compared to those with stable coronary artery disease. PMID- 27275154 TI - Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction. AB - BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a marker for acute kidney injury and cardiovascular outcome. However, the relative importance of inflammation versus kidney function on plasma NGAL levels is uncertain, making the interpretation of plasma NGAL unclear. Accordingly, we investigated the relationship between plasma NGAL, inflammation and kidney function in patients with myocardial infarction (MI). METHODS: We prospectively included 584 patients with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2006 to 2008. Blood samples were drawn immediately before PCI. Additionally, we included 42 patients who had 4 blood samples drawn before and after PCI. Plasma NGAL was measured using a time resolved immunofluorometric assay. Cross-sectional analyses were performed in these two single-center, prospective study cohorts. RESULTS: Estimated glomerular filtration rate (eGFR) was associated significantly more strongly with plasma NGAL when eGFR was abnormal compared to normal eGFR: a decrease in eGFR of 10 ml/min was associated with an increase in NGAL of 27% (18-36%) versus 4% (1-7%), respectively (p < 0.001). Leukocyte count and C-reactive protein were the main determinants of plasma NGAL in patients with normal eGFR, whereas eGFR was the main determinant at reduced kidney function. CONCLUSIONS: eGFR determines the association of NGAL with either inflammation or kidney function; in patients with normal eGFR, plasma NGAL reflects inflammation but when eGFR is reduced, plasma NGAL reflects kidney function, highlighting the dual perception of plasma NGAL. From a clinical perspective, eGFR may be used to guide the interpretation of elevated NGAL levels in patients with STEMI. PMID- 27275155 TI - Serum Uric Acid Levels and Renal Impairment among ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Intervention. AB - BACKGROUND: Elevated serum uric acid (UA) levels are associated with adverse outcomes in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). However, the relation between UA and acute kidney injury (AKI) in this population is unclear. We evaluated the effect of elevated UA levels on the risk to develop AKI among consecutive STEMI patients treated with primary PCI. METHODS: We performed a retrospective analysis of 1,372 consecutive patients admitted with the diagnosis of STEMI between January 2008 and February 2015. Patients were stratified into quartiles according to UA levels as follows: quartile 1, <4.7 mg/dl; quartile 2, 4.8 to <5.6 mg/dl; quartile 3, 5.7 to <6.6 mg/dl, and quartile 4, >6.7 mg/dl. RESULTS: STEMI patients with elevated UA levels had a higher frequency of AKI (4 vs. 6% vs. 10 vs. 24%; p < 0.001). In a subgroup analysis of patients with reduced baseline estimated glomerular filtration rate (<=60 ml/min/1.73 m(2)), an elevated UA level was associated with a significant risk to develop AKI, with 46% of patients developing AKI in the highest UA quartile. In a multivariate logistic regression model, for every 1-mg/dl increase in the UA concentration, the adjusted risk for AKI increased by 46% (OR = 1.46, 95% CI 1.18-1.66; p < 0.001). CONCLUSIONS: Among STEMI patients undergoing primary PCI, elevated UA levels are an independent predictor of AKI. PMID- 27275156 TI - Psychological Distress and Hypertension: Results from the National Health Interview Survey for 2004-2013. AB - BACKGROUND/AIMS: Psychological conditions are increasingly linked with cardiovascular disorders. We aimed to examine the association between psychological distress and hypertension. METHODS: We used data from the National Health Interview Survey for 2004-2013. Hypertension was self-reported and the 6 item Kessler Psychological Distress Scale was used to assess psychological distress (a score >=13 indicated distress). We used a logistic regression model to test the assumption that hypertension was associated with psychological distress. RESULTS: Among the study participants completing the survey (n = 288,784), 51% were female; the overall mean age (+/-SEM) was 35.3 +/- 0.02 years and the mean body mass index was 27.5 +/- 0.01. In the entire sample, the prevalence of psychological distress was 3.2%. The adjusted odds of reporting hypertension in psychologically distressed individuals was 1.53 (95% CI = 1.31 1.80, p = 0.01). CONCLUSION: The findings suggest that psychological distress is associated with higher odds of hypertension after adjusting for other risk factors for high blood pressure. Further studies are needed to confirm these findings and to elucidate the mechanisms by which stress increases hypertension risk. PMID- 27275157 TI - Circadian Blood Pressure Rhythm Is Changed by Improvement in Hypoalbuminemia and Massive Proteinuria in Patients with Minimal Change Nephrotic Syndrome. AB - BACKGROUND: Proteinuria and nighttime blood pressure (BP) elevation are notable risk markers of chronic kidney disease and correlate closely with each other. However, daily urinary protein excretion (UPE) always fluctuates. In patients with minimal change nephrotic syndrome (MCNS), serum albumin concentrations (SAC) decrease but fluctuate less than UPE. We evaluated whether SAC is a reliable marker for proteinuria, and compared the relations among circadian BP changes, SAC, and UPE. METHODS: In patients with MCNS (12 men and 11 women, 43 +/- 18 years), blood and spot urine samples were collected on three consecutive days before treatment, and 24-hour BP was also measured on the three days. Then, an intervention study was conducted in the patients to examine circadian BP changes induced by treatment. Sleeping/waking BP ratio was analyzed as an indicator of circadian BP rhythm. RESULTS: In the three-day measurements before treatment, mean coefficient of variation, an index of dispersion of data, for SAC was 7.4 +/ 7.4%, which was markedly lower (p < 0.01) than 35.7 +/- 15.4% for UPE. SAC correlated inversely with sleeping/waking systolic and diastolic BP ratios on all three days, whereas UPE did not correlate significantly with sleeping/waking diastolic BP ratio on day 3. Sleeping/waking systolic and diastolic BP ratios were 96 +/- 5 and 95 +/- 6%, and were higher (p < 0.05) than in healthy subjects (89 +/- 8 and 88 +/- 10%). Treatment improved hyperproteinuria and hypoalbuminemia, and was accompanied by decreases (p < 0.05) in sleeping and waking systolic/diastolic BP ratio to 91 +/- 8 and 89 +/- 9%. CONCLUSION: These findings suggest that reduced SAC in patients with proteinuria is associated with disrupted circadian BP rhythm. PMID- 27275158 TI - Risk Factors for Acute Kidney Injury after Coronary Artery Bypass Surgery and Its Detection Using Neutrophil Gelatinase-Associated Lipocalin. AB - INTRODUCTION: Acute kidney injury (AKI) is an important complication of cardiac surgery due to its high mortality. The aim of the present study was to detect the factors leading to AKI in patients who underwent coronary artery bypass surgery (CABS) and also to determine the optimal timing for detecting AKI using the biomarker neutrophil gelatinase-associated lipocalin (NGAL). MATERIALS AND METHODS: The records of 375 patients who underwent CABS were reviewed in this case-control study. Ejection fraction (EF), common carotid artery intima-media thickness (CCA-IMT) and cross-clamp (C-C) time of the patients were recorded. Blood samples were taken from all patients on preoperative day 1 as well as 6, 12, 24, 36, 48 h and 7 days after operation. Biochemical parameters were studied in patients with and without AKI. RESULTS: According to the Risk Injury Failure Loss End Stage criteria, 24 patients had renal risk, 17 had injury and 4 had failure. Postoperative 24-hour serum creatinine levels indicated the risk of renal dysfunction for only 4 patients in the AKI group. CCA-IMT, C-C time, haematocrit (HCT) and preoperative interleukin-6 levels were significantly higher in the AKI group than in the non-AKI group. Postoperative 6- and 12-hour NGAL levels in the AKI group correlated with postoperative 36-hour serum creatinine levels. The optimal cut-off values for postoperative 6- and 12-hour NGAL test were 310 and 283 ng/ml, respectively. The area under the curve was higher in the 12-hour NGAL test (p < 0.0086). CONCLUSION: The number of stenotic coronary arteries, EF, CCA-IMT and HCT are all important risk factors. Early postoperative NGAL results were highly specific for the early recognition of AKI. PMID- 27275159 TI - Clinical and Echocardiographic Factors Associated with Right Ventricular Systolic Dysfunction in Hemodialysis Patients. AB - BACKGROUND: Chronic kidney disease is a disorder of epidemic proportions that impairs cardiac function. Cardiovascular diseases are the leading cause of death in hemodialysis patients, and the understanding of new nontraditional predictors of mortality could improve their outcomes. Right ventricular systolic dysfunction (RVSD) has recently been recognized as a predictor of cardiovascular death in heart failure and hemodialysis patients. However, the factors contributing to RVSD in hemodialysis patients remain unknown. The aim of this study was to evaluate the clinical and echocardiographic factors associated with RVSD in hemodialysis patients. METHODS: A cross-sectional study was conducted in which 100 outpatients with end-stage renal disease on chronic hemodialysis were evaluated. A transthoracic echocardiographic examination was performed at optimal dry weight. Right ventricular systolic function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Clinical and echocardiographic data were recorded for each patient. A multivariate linear logistic regression was created using RVSD (TAPSE <14 mm) as the dependent variable. RESULTS: Fifteen patients with RVSD and 85 patients without RVSD were analyzed. TAPSE had a positive correlation with left ventricular ejection fraction (LVEF) and myocardial relaxation velocity. Independent contributors to RVSD were LVEF (OR 1.14, 95% CI 1.05-1.26), left ventricular mass index (OR 1.02, 95% CI 1.00-1.04), and myocardial relaxation velocity (OR 1.81, 95% CI 1.18-3.19). CONCLUSIONS: Echocardiographic factors were significant contributors to RVSD. These measurements could be included as part of the routine workup in all end-stage renal disease patients on hemodialysis. PMID- 27275160 TI - Risk Factors for Acute Kidney Injury after Cardiovascular Surgery: Evidence from 2,157 Cases and 49,777 Controls - A Meta-Analysis. AB - PURPOSE: Cardiovascular surgery-associated acute kidney injury (AKI-CS) contributes to mortality and morbidity. However, risk factors accelerating its development are unclear. We identified risk factors for AKI-CS in patients with cardiopulmonary bypass in the hospital surgical intensive care unit to predict and minimize renal complication in future cardiac surgery. METHODS: We analyzed data from 14 case-control studies published prior to June 2014 and indexed in Science Citation Index, PubMed, and other databases to determine the major risk factors for AKI-CS. RESULTS: Analyzed risk factors were divided into three groups: preoperative, intraoperative and postoperative. Preoperative factors included: age (OR, 4.87; 95% CI, 3.50-6.24), NYHA class III/IV (OR, 2.53; 95% CI, 1.32-4.86), hypertension (OR, 1.68; 95% CI, 1.44-1.97), preoperative creatinine (OR, 0.66; 95% CI, 0.18-1.14), peripheral vascular disease (OR, 1.31 95% CI, 1.09 1.57), respiratory system disease (OR, 1.29; 95% CI, 1.10-1.50), diabetes mellitus (OR, 1.52; 95% CI, 1.07-2.16), and cerebrovascular disease (OR, 2.13; 95% CI, 1.11-4.09). Intraoperative factors were: cardiopulmonary bypass time (OR, 33.78; 95% CI, 23.15-44.41), aortic clamping time (OR, 13.24; 95% CI, 7.78 18.69), use of intra-aortic balloon pump (OR, 4.44; 95% CI, 2.37-8.30), and type of surgery (OR, 1.01; 95% CI, 0.43-2.39). Postoperative factors were: infection (OR, 3.58; 95% CI, 1.43-8.97), redo operation (OR, 2.57; 95% CI, 1.75-3.78), emergency surgery (OR, 4.76; 95% CI, 3.05-7.43), and low cardiac output (OR, 2.30; 95% CI, 1.05-5.04). CONCLUSIONS: Our results support that preoperative, intraoperative, and postoperative factors are associated with AKI-CS. Ejection fraction, BMI, acute myocardial infarction, type of surgery, and congestive heart failure were not absolutely associated with AKI. PMID- 27275161 TI - Angiogenic Factors and Risks of Technique Failure and Cardiovascular Events in Patients Receiving Peritoneal Dialysis. AB - BACKGROUND: Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family that acts as a pleiotropic cytokine capable of stimulating angiogenesis and accelerating atherogenesis. Soluble fms-like tyrosine kinase-1 (sFlt-1) antagonizes PlGF action. Higher levels of PlGF and sFlt-1 have been associated with cardiovascular events in patients with chronic kidney disease, yet little is known about their relationship with adverse outcomes in patients on peritoneal dialysis (PD). The aim of this study was to investigate the association of PlGF and sFlt-1 with technique survival and cardiovascular events. METHODS: We measured serum levels of PlGF and plasma levels of sFlt-1 in 40 PD patients at Nara Medical University. RESULTS: PlGF and sFlt-1 levels were significantly correlated with the dialysate-to-plasma ratio of creatinine (r = 0.342, p = 0.04 and r = 0.554, p < 0.001) although PlGF and sFlt 1 levels were not correlated with total creatinine clearance and total Kt/V. Additionally, both PlGF and sFlt-1 levels were significantly higher in patients with high transport membranes compared to those without (p = 0.039 and p < 0.001, respectively). Patients with PlGF levels above the median had lower technique survival and higher incidence of cardiovascular events than patients with levels below the median, with hazard ratios of 11.9 and 7.7, respectively, in univariate Cox regression analysis. However, sFlt-1 levels were not associated with technique survival or cardiovascular events (p = 0.11 and p = 0.10, respectively). CONCLUSION: Elevated PlGF and sFlt-1 are significantly associated with high transport membrane status. PlGF may be a useful predictor of technique survival and cardiovascular events in PD patients. PMID- 27275162 TI - Renal Effects and Carcinogenicity of Occupational Exposure to Uranium: A Meta Analysis. AB - PURPOSE: Uranium is a heavy metal with alpha radioactivity. We state the hypothesis that uranium exposure is harmful to human kidneys and carcinogenic to body tissues. Therefore, we review epidemiological studies from people with known long-lasting uranium exposure. MATERIALS AND METHODS: Three meta-analyses are performed using clinical studies published in the PubMed database and applying RevMan 5.3 from the Cochrane Collaboration to calculate the outcome. The first two meta-analyses examine the standardized mortality ratio (SMR) and the standardized incidence ratio for any cancers of uranium workers who were operating in areas ranging from uranium processing to the assembly of final uranium products. The third meta-analysis evaluates the nephrotoxic risk in uranium workers as well as soldiers and of individuals with exposure to drinking water containing uranium. RESULTS: Overall and contrasting to our hypothesis, the tumor risk is significantly lower for uranium workers than for control groups (SMR = 0.90 with a 95% confidence interval of 0.84 to 0.96). In addition and also contrasting to our hypothesis, the risk of nephrotoxicity is not increased either. This holds for both the incidence and the mortality due to renal cell carcinoma or due to acute kidney injury or chronic kidney disease. In contrast, a significantly better creatinine clearance is found for the uranium cohort as compared to the control groups (mean difference = 7.66 with a 95% confidence interval of 0.12 to 15.2). CONCLUSION: Our hypothesis that a chronic uranium exposure is associated with an increased risk of cancer mortality or of kidney failure is refuted by clinical data. The decreased risk may result from better medical surveillance of uranium workers. PMID- 27275163 TI - The Liver MicroRNA Expression Profiles Associated With Chronic Hepatitis C Virus (HCV) Genotype-4 Infection: A Preliminary Study. AB - BACKGROUND: MicroRNAs (miRNAs) have been repeatedly shown to play important roles in liver pathologies, including hepatitis, liver cirrhosis, and liver cancer. Egypt has the highest hepatitis C virus (HCV) infection rate worldwide, predominantly involving genotype-4. OBJECTIVES: In this study, we attempted to characterize the miRNA profile of the poorly studied genotype 4 of HCV in chronically infected Egyptian patients to obtain a better understanding of the disease and its complications and help in the design of better management protocols. PATIENTS AND METHODS: We analyzed the expression levels of a selected panel of 94 miRNAs in fresh liver biopsies collected from 50 Egyptian patients diagnosed with chronic HCV infection using quantitative real-time polymerase chain reaction (PCR) assay. Non-parametric tests were used to analyze the expression level of each miRNA and association with the clinicopathological features of enrolled patients in this study. RESULTS: Our results revealed differential expression levels of the analyzed miRNAs compared to the normal controls. Twenty-seven miRNAs (including miR-105, miR-147, miR-149-3p, and miR 196b) showed up-regulation, while 17 miRNAs (including miR-21, miR-122, miR-199a 3p, and miR-223) showed down-regulation. An inverse correlation was observed between levels of miR-95, miR-130a, and miR-142-5p with the blood albumin level. Increased expression levels of seven miRNAs (miR-29c, miR-30c, miR-126, miR-145, miR-199a, miR-199a-3p, and miR-222) were observed with severe chronic hepatic inflammation. Several deregulated miRNAs found in this study have been previously linked to chronic liver inflammation and the risk of hepatocellular carcinoma (HCC) development. CONCLUSIONS: The identified expression profiles of some examined miRNAs might offer important points to consider for the treatment of naive patients and the management of chronically infected HCV patients in Egypt and around the world. PMID- 27275164 TI - Next Steps Toward Eradication of Hepatitis C in the Era of Direct Acting Antivirals. AB - CONTEXT: After the introduction of safe and highly effective hepatitis C virus (HCV) treatments, eradication of HCV in the next 20 years is the ultimate goal. Since 2011, the advent of first generation direct acting antivirals (DAAs) were started and followed by the introduction of a new wave of DAAs in 2013 which exhibit outstanding efficacy. It is obvious that the eradication of hepatitis C is not restricted to development of DAAs. EVIDENCE ACQUISITION: An electronic search of available literature published was conducted in all peer-reviewed journal indexed in PubMed, Scopus and Google scholar. The literature search was done among articles related treatment of hepatitis C with DAAs in different patient groups with mass screening of the patients and cost benefit of new treatments as main key words. RESULTS: There are major steps that should be taken to eradicate HCV, including (1) the development of screening strategies, particularly for groups such as intravenous drug users and recipients of blood or blood products before the introduction of HCV screening in donors; (2) the development of strategies to overcome issues with the high cost of recently introduced treatments; (3) special attention to special patient groups, such as HIV/HCV co-infection, hemophilia, thalassemia, hemodialysis, and liver-transplant patients; and (4) development of preventive strategies, such as the development of an efficient HCV vaccine, special attention to harm reduction in high-risk groups, and promotion of mass awareness of HCV. CONCLUSIONS: The eradication of HCV will require significant governmental financial investment for screening, prevention, and treatment of infected patients. Although, we have a long way to eradication of HCV, the next steps could be including proper planning to patient finding, availability of new treatments to all patients and development of HCV prevention strategies such as vaccines. PMID- 27275166 TI - Angiotensin Receptor Blocker for Stroke Prevention in Atrial Fibrillation: beyond Blood Pressure Lowering? PMID- 27275165 TI - 2015 Korean Guidelines for the Management of Dyslipidemia: Executive Summary (English Translation). PMID- 27275167 TI - Antioxidative Activity after Rosuvastatin Treatment in Patients with Stable Ischemic Heart Disease and Decreased High Density Lipoprotein Cholesterol. AB - BACKGROUND AND OBJECTIVES: The clinical significance of statin-induced high density lipoprotein cholesterol (HDL-C) changes is not well known. We investigated whether rosuvastatin-induced HDL-C changes can influence the anti oxidative action of high-density lipoprotein particle. SUBJECTS AND METHODS: A total of 240 patients with stable ischemic heart disease were studied. Anti oxidative property was assessed by paraoxonase 1 (PON1) activity. We compared the lipid profile and PON1 activity at baseline and at 8 weeks after rosuvastatin 10 mg treatment. RESULTS: Rosuvastatin treatment increased the mean HDL-C concentration by 1.9+/-9.2 mg/dL (6.4+/-21.4%). HDL-C increased in 138 patients (57.5%), but decreased in 102 patients (42.5%) after statin treatment. PON1 activity increased to 19.1% in all patients. In both, the patients with increased HDL-C and with decreased HDL-C, PON1 activity significantly increased after rosuvastatin treatment (+19.3% in increased HDL-C responder; p=0.018, +18.8% in decreased HDL-C responder; p=0.045 by paired t-test). Baseline PON1 activity modestly correlated with HDL-C levels (r=0.248, p=0.009); however, the PON1 activity evaluated during the course of the treatment did not correlate with HDL C levels (r=0.153, p=0.075). CONCLUSION: Rosuvastatin treatment improved the anti oxidative properties as assessed by PON1 activity, regardless of on-treatment HDL C levels, in patients with stable ischemic heart disease. PMID- 27275168 TI - Differential Clinical Implications of High-Degree Atrioventricular Block Complicating ST-Segment Elevation Myocardial Infarction according to the Location of Infarction in the Era of Primary Percutaneous Coronary Intervention. AB - BACKGROUND AND OBJECTIVES: The clinical implication of high-degree (second- and third-degree) atrioventricular block (HAVB) complicating ST-segment elevation myocardial infarction (STEMI) is ripe for investigation in this era of primary percutaneous coronary intervention (PCI). We sought to address the incidence, predictors and prognosis of HAVB according to the location of infarct in STEMI patients treated with primary PCI. SUBJECTS AND METHODS: A total of 16536 STEMI patients (anterior infarction: n=9354, inferior infarction: n=7692) treated with primary PCI were enrolled from a multicenter registry. We compared in-hospital mortality between patients with HAVB and those without HAVB with anterior or inferior infarction, separately. Multivariate analyses were performed to unearth predictors of HAVB and to identify whether HAVB is independently associated with in-hospital mortality. RESULTS: STEMI patients with HAVB showed higher in hospital mortality than those without HAVB in both anterior (hazard ratio [HR]=9.821, 95% confidence interval [CI]: 4.946-19.503, p<0.001) and inferior infarction (HR=2.819, 95% CI: 2.076-3.827, p<0.001). In multivariate analyses, HAVB was associated with increased in-hospital mortality in anterior myocardial infarction (HR=19.264, 95% CI: 5.804-63.936, p<0.001). However, HAVB in inferior infarction was not an independent predictor of increased in-hospital mortality (HR=1.014, 95% CI: 0.547-1.985, p=0.901). CONCLUSION: In this era of primary PCI, the prognostic impact of HAVB is different according to the location of infarction. Because of recent improvements in reperfusion strategy, the negative prognostic impact of HAVB in inferior STEMI is no longer prominent. PMID- 27275169 TI - Differential Benefit of Statin in Secondary Prevention of Acute Myocardial Infarction according to the Level of Triglyceride and High Density Lipoprotein Cholesterol. AB - BACKGROUND AND OBJECTIVES: The differential benefit of statin according to the state of dyslipidemia has been sparsely investigated. We sought to address the efficacy of statin in secondary prevention of myocardial infarction (MI) according to the level of triglyceride and high density lipoprotein cholesterol (HDL-C) on admission. SUBJECTS AND METHODS: Acute MI patients (24653) were enrolled and the total patients were divided according to level of triglyceride and HDL-C on admission: group A (HDL-C>=40 mg/dL and triglyceride<150 mg/dL; n=11819), group B (HDL-C>=40 mg/dL and triglyceride>=150 mg/dL; n=3329), group C (HDL-C<40 mg/dL and triglyceride<150 mg/dL; n=6062), and group D (HDL-C<40 mg/dL & triglyceride>=150 mg/dL; n=3443). We evaluated the differential efficacy of statin according to the presence or absence of component of dyslipidemia. The primary end points were major adverse cardiac events (MACE) for 2 years. RESULTS: Statin therapy significantly reduced the risk of MACE in group A (hazard ratio=0.676; 95% confidence interval: 0.582-0.785; p<0.001). However, the efficacy of statin was not prominent in groups B, C, or D. In a propensity matched population, the result was similar. In particular, the benefit of statin in group A was different compared with group D (interaction p=0.042). CONCLUSION: The benefit of statin in patients with MI was different according to the presence or absence of dyslipidemia. In particular, because of the insufficient benefit of statin in patients with MI and dyslipidemia, a different lipid-lowering strategy is necessary in these patients. PMID- 27275170 TI - Effects of Angiotensin-II Receptor Blocker on Inhibition of Thrombogenicity in a Canine Atrial Fibrillation Model. AB - BACKGROUND AND OBJECTIVES: Angiotensin-II receptor blockers (ARBs) are known to reduce the development of atrial fibrillation (AF) through reverse-remodeling. However, the effect of ARBs on thrombogenicity in AF remains unknown. MATERIALS AND METHODS: Twelve dogs were assigned to control (n=4), ARB (candesartan cilexitil 10 mg/kg/day p.o., 12 weeks; n=4), or sham (n=4) groups. Sustained AF was induced by rapid atrial pacing. Both arterial and venous serum levels of tissue inhibitor of matrix metalloproteinase-1, von Willebrand factor, P selectin, and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and during AF (0, 4, and 12 weeks) with enzyme-linked immunosorbent assay. Biopsies from both atria including the appendages were performed to semi quantitatively assess endocardial and myocardial fibrosis after 12 weeks. RESULTS: The serum levels of bio-markers were not significantly different at baseline or during AF between the control and the candesartan groups. The levels were not significantly different over time, but there was a trend toward a decrease in arterial VCAM-1 from 4 to 12 weeks in the candesartan group compared to the control group. The grades of endocardial fibrosis after 12 weeks but not those of myocardial fibrosis were slightly reduced in the candesartan group compared to the control group. CONCLUSION: This study did not show that the ARB candesartan significantly reverses thrombogenicity or fibrosis during AF. Future studies using a larger number of subjects are warranted to determine the therapeutic effect of renin-angiotensin-aldosterone system blockade on prothrombogenic processes in AF. PMID- 27275171 TI - Effects of Trimetazidine on T Wave Alternans in Stable Coronary Artery Disease. AB - BACKGROUND AND OBJECTIVES: Studies reveal that the microvolt T wave alternans (MTWA) test has a high negative predictive value for arrhythmic mortality among patients with ischemic or non-ischemic cardiomyopathy. In this study, we investigate the effects of trimetazidine treatment on MTWA and several echocardiographic parameters in patients with stable coronary artery disease. SUBJECTS AND METHODS: One hundred patients (23 females, mean age 55.6+/-9.2 years) with stable ischemic heart disease were included in the study group. Twenty-five age- and sex-matched patients with stable coronary artery disease formed the control group. All patients were stable with medical treatment, and had no active complaints. Trimetazidine, 60 mg/day, was added to their current treatment for a minimum three months in the study group and the control group received no additional treatment. Pre- and post-treatment MTWA values were measured by 24 hour Holter testing. Left ventricular systolic and diastolic functions were assessed by echocardiography. RESULTS: After trimetazidine treatment, several echocardiographic parameters related with diastolic dysfunction significantly improved. MTWA has been found to be significantly improved after trimethazidine treatment (63+/-8 MUV vs. 53+/-7 MUV, p<0.001). Abnormal MTWA was present in 29 and 11 patients pre- and post-treatment, respectively (p< 0.001). CONCLUSION: Trimetazidine improves MTWA, a non-invasive determinant of electrical instability. Moreover, several echocardiographic parameters related with left ventricular functions also improved. Thus, we can conclude that trimetazidine may be an effective agent to prevent arrhythmic complications and improve myocardial functions in patients with stable coronary artery disease. PMID- 27275172 TI - Two Distinct Responses of Left Ventricular End-Diastolic Pressure to Leg-Raise Exercise in Euvolemic Patients with Exertional Dyspnea. AB - BACKGROUND AND OBJECTIVES: Few studies have invasively assessed diastolic functional reserve and serial changes in left ventricular hemodynamics in euvolemic patients with exertional dyspnea. In this study, sequential changes in left ventricular end-diastolic pressure (LVEDP) to leg-raise exercise were measured invasively in patients with early heart failure with preserved ejection fraction (HFpEF) to determine the association between these serial changes and echocardiographic results or clinical features. SUBJECTS AND METHODS: During their hospital stay, 181 patients with early HFpEF underwent left cardiac catheterization, coronary angiography, and transthoracic echocardiography (TTE). Leg-raise exercise was performed in two stages: during cardiac catheterization and again during TTE. RESULTS: Compared with the initial values, all the invasively measured LVEDP values increased significantly during the leg-raise exercise, whereas the septal e/e' ratio remained unchanged. Active leg-raise led to increased LVEDP, which caused dyspnea. The severity of symptoms correlated with the level and extent of changes in LVEDP. At the end of active leg-raise, LVEDP decreased in 40 patients (22.1%), who were younger and had significantly lower e/e' ratios. On multivariate analysis to predict the response of LVEDP to active leg-raise, age and the septal e/e' ratio remained significant predictors. CONCLUSION: Despite having similar LVEDP values at rest, patients may respond to exercise with different LVEDP levels and clinical manifestations, depending on their diastolic capacity. The leg-raise exercise in early HFpEF can elucidate individual diastolic profiles, and the LVEDP response to the leg-raise test may serve as a useful criterion in stratifying patients with early HFpEF with respect to functional reserve. PMID- 27275173 TI - Higher Blood Pressure Variability in White Coat Hypertension; from the Korean Ambulatory Blood Pressure Monitoring Registry. AB - BACKGROUND AND OBJECTIVES: Blood pressure variability (BPV) was recently shown to be a risk factor of stroke. White coat hypertension (WCH) used to be regarded as innocuous, but one long-term follow-up study reported that WCH increased stroke rate compared to normotension (NT). In this study, we aimed to evaluate the relationship between WCH and BPV. SUBJECTS AND METHODS: We analyzed 1398 subjects from the Korean Ambulatory Blood Pressure Registry, who were divided into NT (n=364), masked hypertension (n=122), white coat hypertension (n=254), and sustained hypertension (n=658) groups. RESULTS: Baseline characteristics were similar among groups. The average real variability (ARV), a highly sensitive BPV parameter, was highest in the WCH group, followed by the sustained hypertension, masked hypertension, and NT groups. The results persisted after being adjusted for covariates. The WCH vs. sustained hypertension results (adjusted mean+/ standard error) were as follows: 24-h systolic ARV, 22.9+/-0.8 vs. 19.4+/-0.6; 24 h diastolic ARV, 16.8+/-0.6 vs. 14.3+/-0.5; daytime systolic ARV, 21.8+/-0.8 vs. 16.8+/-0.6; and daytime diastolic ARV, 16.2+/-0.6 vs. 13.4+/-0.5 (p<0.001 for all comparisons). CONCLUSION: From the registry data, we found that subjects with WCH or masked hypertension had higher BPV than NT. However, long-term follow-up data assessing the clinical influences of WCH on stroke are needed. PMID- 27275174 TI - Inter-Arm Difference in Brachial Blood Pressure in the General Population of Koreans. AB - BACKGROUND AND OBJECTIVES: We investigated the inter-arm difference in blood pressure of the general Korean population to identify associated factors. SUBJECTS AND METHODS: A total of 806 participants aged 30 to 64 years without history of major cardiovascular disease were analyzed in this cross-sectional study. They participated in the Cardiovascular and Metabolic Disease Etiology Research Center cohort study that began in 2013. Brachial blood pressure was measured simultaneously for both arms using an automated oscillometric device equipped with two cuffs in seated position. After five minutes of rest, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured three times. The average of the three measurements was used for analysis. Multivariate logistic regression models were used to identify factors associated with inter arm differences in blood pressure. RESULTS: The mean inter-arm difference was 3.3 mmHg for SBP and 2.0 mmHg for DBP. Large inter-arm differences (>=10 mmHg) in SBP and in DBP were found in 3.7% and 0.9% of subjects, respectively. A large inter arm difference in SBP was associated with mean SBP (p=0.002) and C-reactive protein (p=0.014) while a large inter-arm different in DBP was only associated with body mass index (p=0.015). Sex, age, and anti-hypertensive medication use were not associated with differences in inter-arm blood pressure. CONCLUSION: Large inter-arm difference in blood pressure is only present in a small portion of healthy Korean adults. Our findings suggest that high SBP, chronic inflammation, and obesity may be associated with larger difference in inter-arm blood pressure. PMID- 27275175 TI - Medication Adherence and the Occurrence of Complications in Patients with Newly Diagnosed Hypertension. AB - BACKGROUND AND OBJECTIVES: In this retrospective cohort study, we sought to elucidate the relationship between medication adherence (MA) and the incidence of complications in patients with newly diagnosed hypertension. SUBJECTS AND METHODS: Using claims data from the National Health Insurance Service, we measured health outcomes based on levels of MA, analyzed the incidence of complications in patients with a good MA, and clarified factors that may affect or predict MA. RESULTS: In 2008, a total of 4294773 patients were diagnosed with hypertension and were subsequently prescribed anti-hypertensive medications. In the present study, we enrolled 564782 patients who met our inclusion/exclusion criteria. The 40-59% medication possession ratio (MPR) group had a 1.36 times higher risk of developing complications (95% confidence interval [CI]: 1.27-1.45) than did the MPR>= 80% group, as revealed through Cox's proportional hazards analysis. Similarly, the <20% MPR group was 2.01 times more likely to develop complications than the good MA group (95% CI: 1.82-2.23). Overall, patients who had a lower level of MA had a higher risk of developing complications. CONCLUSION: Our results demonstrate that MA is tightly correlated with hypertension health outcomes. Improving MA could be one strategy for reducing the risk of cerebrovascular disease complications and the loss of productivity in these patients. PMID- 27275176 TI - Obesity and Hypertension in Association with Diastolic Dysfunction Could Reduce Exercise Capacity. AB - BACKGROUND AND OBJECTIVES: Empirical evidence is lacking on the cumulative disease burden of obesity and hypertension and its impact on cardiac function and exercise capacity. The purpose of this study was to determine whether the presence of obesity and hypertension together was associated with cardiac dysfunction and exercise capacity. SUBJECTS AND METHODS: Using a retrospective study design, medical records were reviewed for echocardiographic and treadmill exercise stress test data. Subjects were grouped according to four categories: normal control, obese, hypertensive, or obese and hypertensive. RESULTS: Obese, hypertensive persons showed significantly lower Ea and E/A ratio and greater E/Ea ratio, deceleration time, left ventricular (LV) mass, and LV mass index compared to their counter parts (normal control, obese and/or hypertensive) (all p<0.05), after controlling for age and sex. After controlling for age and sex, significant differences in exercise capacity indices were found, with the obese group having shorter exercise time, lower metabolic equivalents, and lower maximal oxygen uptake than the normal control, hypertensive, or both groups (all p<0.05). The hypertensive or obese and hypertensive group had greater maximal blood pressure compared with the normal control group (all p<0.001). Obese and hypertensive persons were approximately three times more likely to have diastolic dysfunction (odd ratio=2.96, p=0.001), when compared to the reference group (normotensive, non-obese, or hypertensive only persons). CONCLUSION: Diastolic dysfunction was associated with obesity and/or hypertension. The cumulative risk of obesity and hypertension and their impact on diastolic dysfunction which could be modifiable could reduce exercise capacity. PMID- 27275177 TI - Levosimendan Reduces Lung Injury in a Canine Model of Cardiopulmonary Bypass. AB - BACKGROUND AND OBJECTIVES: To explore the lung-protective effect of levosimendan (LS) during cardiopulmonary bypass in a canine model by determining the wet/dry weight (W/D) ratio of lung tissue, malonaldehyde (MDA) and superoxide dismutase (SOD) concentrations, and performing a histological evaluation. MATERIALS AND METHODS: Thirty-two canines were divided randomly into four groups and underwent a routine aortic cross-clamping cardiopulmonary bypass procedure for 1 h, followed by recovery for 2 h. Animals were handled as follows: group C (means control group), no special treatment after aortic cross clamping; group P (means pulmonary artery perfusion group), pulmonary artery perfusion with cold oxygenated blood after aortic cross clamping; group LSIV (means intravenous injection of LS group), intravenous injection of LS (65 ug/kg) before thoracotomy, and the rest of the procedure was identical to the control group; group LPS (means pulmonary perfusion with LS group), pulmonary perfusion with cold oxygenated blood combined with LS (65 ug/kg) after aortic cross clamping. Lung tissues were removed and subjected to evaluation of pathological alterations, W/D ratio and MDA and SOD concentrations. RESULTS: In group C, the W/D ratio and MDA concentration were higher, while the SOD concentrations were lower (p<0.05). Compared with groups P and LSIV, the MDA concentration was lower in group LPS, while that of SOD was higher (p<0.05); Light and electron microscopy indicated that LS intervention reduced impairment of lung tissues. CONCLUSION: Our findings suggest that LS plays an important role in protecting lung tissues. PMID- 27275178 TI - Abdominal Wall Hematoma as a Rare Complication following Percutaneous Coronary Intervention. AB - Abdominal wall hematoma is a rare but potentially serious vascular complication that may develop after coronary angiographic procedures. In particular, an oblique muscle hematoma caused by an injury of the circumflex iliac artery is very rare, yet can be managed by conservative treatment including hydration and transfusion. However, when active bleeding continues, angiographic embolization or surgery might be needed. In this study, we report an uncommon case of injury to the circumflex iliac artery by an inappropriate introduction of the hydrophilic guidewire during the performance of a percutaneous coronary intervention. PMID- 27275179 TI - Preservation of Internal Iliac Artery after Endovascular Repair of Common Iliac Artery Dissection Using Modified Fenestrated Stent Graft. AB - Standard endovascular repair of iliac/aortoiliac pathologies can lead to complications, such as buttock claudication, colon ischemia and erectile dysfunction. Branch grafts have been developed but require at least 6 weeks for customization and are not currently available in China; they are also quite expensive. To our knowledge, modified fenestrated stent grafts (MFSGs) are a safe and effective alternative for treating patients with juxtarenal aneurysms. Most MFSGs are used for the preservation of renal and left subclavian arteries. Few cases of MFSGs have been reported in the treatment of iliac pathologies. The use of an MFSG is decided on a case-by-case basis. This report presents our first clinical use of an MFSG for preservation of the internal iliac artery. PMID- 27275180 TI - Endovascular Treatment of Multilevel Chronic Total Occlusion Using a Stent Puncture Technique in Buerger's Disease. AB - We reported a patient with Buerger's disease who presented with critical limb ischemiawith prior recurrent occlusions after multiple surgical and endovascular treatments. Total occlusion of the whole native femoropopliteal and infrapopliteal arteries was observed. The femoropopliteal bypass graft, as well as a stent that was implanted in the mid-popliteal artery, were also occluded. Because of the lack of distal targets for bypass, surgical revascularization was not feasible; therefore, we decided to perform endovascular treatment. To overcome the limitation of vascular access, the previously implanted popliteal stent was directly punctured, and a guide wire was passed through the bypass graft. After the organized thrombus in the bypass graft was aspirated, further recanalization below the popliteal stent down to the plantar arteries was performed successfully. In conclusion, the stent puncture technique is a feasible and safe option for overcoming the limitations of vascular access in patients with multilevel occlusions. PMID- 27275181 TI - Reversal of Pacing-Induced Cardiomyopathy by Normal QRS Axis Pacing. AB - Right ventricular apical pacing has been a commonly used method for placement of permanent pacemaker, but it is known to be associated with ventricular dyssynchrony and may lead to heart failure. Septal pacing could be an alternative method to improve this complication but the results have been conflicting; hence, other strategies are needed. This case is about a patient with pacing-induced cardiomyopathy who showed much improvement after repositioning the leads to a site different from that of normally paced QRS axis. PMID- 27275182 TI - Non-Bacterial Thrombotic Endocarditis in a Patient with Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is frequently associated with various extra-joint complications. Although rare, thromboembolic complications are associated with high morbidity and mortality. We experienced a very rare case of nonbacterial thrombotic endocarditis (NBTE) and subsequent embolic stroke in a patient with RA. A 72-year-old male with a 15-year history of RA suddenly developed neurologic symptoms of vomiting and dizziness. Brain magnetic resonance imaging revealed recently developed multiple cerebellar and cerebral lacunar infarctions. Echocardiography showed a pulsating mitral valve vegetation involving the posterior cusp of the mitral valve leaflet, which was confirmed as NBTE. Immediate anti-coagulation therapy was started. The NBTE lesion disappeared in follow-up echocardiography after 4 weeks of anti-coagulation treatment. PMID- 27275183 TI - Sympathetic Activity Index Should Be Kept in Mind When Assessing Autonomic Tonus. PMID- 27275184 TI - Apelin Levels in Patients with Coronary Artery Ectasia. PMID- 27275185 TI - Erratum: Psychiatric Characteristics of the Cardiac Outpatients with Chest Pain. AB - [This corrects the article on p. 169 in vol. 46, PMID: 27014347.]. PMID- 27275186 TI - Application of a modified drop method for high-resolution pachytene chromosome spreads in two Phalaenopsis species. AB - BACKGROUND: Preparation of good chromosome spreads without cytoplasmic contamination is the crucial step in cytogenetic mapping. To date, cytogenetic research in the Orchidaceae family has been carried out solely on mitotic metaphase chromosomes. Well-spread meiotic pachytene chromosomes can provide higher resolution and fine detail for analysis of chromosomal structure and are also beneficial for chromosomal FISH (fluorescence in situ hybridization) mapping. However, an adequate method for the preparation of meiotic pachytene chromosomes in orchid species has not yet been reported. RESULTS: Two Taiwanese native Phalaenopsis species were selected to test the modified drop method for preparation of meiotic pachytene chromosomes from pollinia. In this modified method, pollinia were ground and treated with an enzyme mixture to completely remove cell walls. Protoplasts were resuspended in ethanol/glacial acetic acid and dropped onto a wet inclined slide of 30 degrees from a height of 0.5 m. The sample was then flowed down the inclined plane to spread the chromosomes. Hundreds of pachytene chromosomes with little to no cytoplasmic contamination were well spread on each slide. We also showed that the resolution of 45S rDNA containing chromosomes at the pachytene stage was up to 20 times higher than that at metaphase. Slides prepared following this modified drop method were amenable to FISH mapping of both 45S and 5S rDNA on pachytene chromosomes and, after FISH, the chromosomal structure remained intact for further analysis. CONCLUSION: This modified drop method is suitable for pachytene spreads from pollinia of Phalaenopsis orchids. The large number and high-resolution pachytene spreads, with little or no cytoplasmic contamination, prepared by the modified drop method could be used for FISH mapping of DNA fragments to accelerate the integration of cytogenetic and molecular research in Phalaenopsis orchids. PMID- 27275187 TI - Advanced SPARQL querying in small molecule databases. AB - BACKGROUND: In recent years, the Resource Description Framework (RDF) and the SPARQL query language have become more widely used in the area of cheminformatics and bioinformatics databases. These technologies allow better interoperability of various data sources and powerful searching facilities. However, we identified several deficiencies that make usage of such RDF databases restrictive or challenging for common users. RESULTS: We extended a SPARQL engine to be able to use special procedures inside SPARQL queries. This allows the user to work with data that cannot be simply precomputed and thus cannot be directly stored in the database. We designed an algorithm that checks a query against data ontology to identify possible user errors. This greatly improves query debugging. We also introduced an approach to visualize retrieved data in a user-friendly way, based on templates describing visualizations of resource classes. To integrate all of our approaches, we developed a simple web application. CONCLUSIONS: Our system was implemented successfully, and we demonstrated its usability on the ChEBI database transformed into RDF form. To demonstrate procedure call functions, we employed compound similarity searching based on OrChem. The application is publicly available at https://bioinfo.uochb.cas.cz/projects/chemRDF. PMID- 27275188 TI - Current Scientific Impact of Ss Cyril and Methodius University of Skopje, Republic of Macedonia in the Scopus Database (1960-2014). AB - AIM: The aim of this study was to analyze current scientific impact of Ss Cyril and Methodius University of Skopje, Republic of Macedonia in the Scopus Database (1960-2014). MATERIAL AND METHODS: Affiliation search of the Scopus database was performed on November 23, 2014 in order to identify published papers from the Ss Cyril and Methodius University of Skopje (UC&M), Republic of Macedonia. A total number of 3960 articles (3055 articles from UC&M, 861 articles from Faculty of Medicine, UC&M, and 144 articles from Faculty of Pharmacy, UC&M) were selected for analysis (1960-2014). SCImago Journal Rank (SJR), Source Normalized Impact per Paper (SNIP) and h-index were calculated from the Scopus database. RESULTS: The number of published papers was sharply increased with maximum of 379 papers in 2012 year. The largest number of papers has been published in Macedonian Journal of Medical Sciences, Journal of Molecular Structure, Lecture Notes in Computer Science, Acta Pharmecutica, and Macedonian Journal of Chemistry and Chemical Engineering. The biggest SJR and SNIP has journal Nephrology Dialysis Transplantation. First three places of the top ten authors belong to Dimirovski GM, Gavrilovska L, and Gusev M. Top three places based on Scopus h-index (total number of published papers) belong to Kocarev L, Stafilov T, and Polenakovic M. The majority of papers originate from UC&M, but significant numbers of papers are affiliated to Faculty of Medicine, Faculty of Pharmacy, and Institute of Chemistry as members of UC&M, as well as Macedonian Academy of Sciences and Arts. Articles are the most dominant type of documents followed by conference papers, and review articles. Medicine is the most represented subject. CONCLUSION: Officials of the Ss Cyril and Methodius University of Skopje should undertake more effective and proactive policies for journal publishers and their Editorial Boards in order to include more journals from UC&M in the Scopus database. PMID- 27275189 TI - Gastrointestinal Colonization with Vancomycin-Resistant Enterococci In Hospitalized and Outpatients. AB - BACKGROUND: The incidence of infection and intestinal colonization with vancomycin resistant enterococci (VRE) is increasing in many countries in the last decade. Concerning the difficult antimicrobial treatment of infections caused by VRE, decreasing the incidence and prevalence of these infections is an important factor in VRE-induced morbidity and mortality control. AIM: To determine the prevalence of gastrointestinal colonization with vancomycin resistant enterococci in hospitalized and outpatients, and to determine the genetic base of the vancomycin resistance in VRE isolates. MATERIAL AND METHODS: Seven hundred and eighty stool specimens were investigated for the gastrointestinal carriage of vancomycin-resistant enterococci (VRE). Susceptibility to vancomycin was tested in all isolates by disk-diffusion test and E-test (AB Biodisk, Sweden). Determined vancomycin resistant enterococci were than tested for detection of vanA, vanB and vanC genes by PCR. RESULTS: Vancomycin resistant strains of enterococci were isolated from 46 (16.1 %) of the 285 hospitalized patients and 5 (7.7 %) of the 65 patients living in the community (p < 0.05). The most of the highly resistant enterococci strains to vancomycin (95.2 %), were identified as E. faecium. Minimal inhibitory concentrations (MICs) to vancomycin in all 39 vanA genotypes of E. faecium and two vanA genotypes of E. fecalis were > 256 MUg/ml. Three vanB genotypes of E. faecium and one vanB genotype of E. faecalis had MICs of 32 MUg/ml. All six vanC genotypes of E. gallinarum had MICs of 8 MUg/ml. All vanA genotypes of VRE were highly resistant to vancomycin, with MICs above 256 MUg/ml. Three vanB genotypes of VR E. faecium and one VR E. fecalis were resistant, with MICs 32 MUg/ml. vanC genotypes of VR E. gallinarum were intermediate resistant to vancomycin with MICs of 8 MUg/ml. CONCLUSIONS: The prevalence of vancomycin resistant enterococci in Republic of Macedonia was 2-fold higher in hospitalized than in outpatients. VanA genotype was dominant in isolates of E. faecium and it was highly associated with the MIC values above the 256 MUg/ml. Since most of the enterococcal infections are endogenous, there is a need for screening the colonization of patient's intestinal flora with VRE at the hospital entry. Identification and genotyping of faecal enterococci, together with their susceptibility testing to vancomycin, could be useful marker for the infection control. PMID- 27275190 TI - Eating Habits and Lifestyles among a Sample of Obese Working Egyptian Women. AB - BACKGROUND: The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories expended. AIM: To figure out food habits and different lifestyle pattern among a sample of Egyptian females working at the National Research Centre. METHODS: A cross-sectional, descriptive study, including 138 overweight and obese Egyptian females (BMI >= 25 Kg/m(2)); working at the National Research Centre; was done. A specific questionnaire was used to gather information regarding lifestyle including dietary habits, physical activity and sedentary behaviour. RESULTS: The prevalence of overweight among the studied subjects was 27%, while that of obesity was 38%. Missing and or infrequent intake of breakfast at home, frequent consumption of snacks, low serving per day of fruits and vegetables with frequent consumption of sweets, fried food, eating while watching TV and sedentary behaviour were all predictors of obesity and overweight among the current sample. CONCLUSION: The present study identified several lifestyle factors and improper dietary habits associated with overweight and obesity among Egyptian females. There is a great need to change these habits to avoid the increasing risk of obesity. A national plan of action to overcome obesity is urgently needed to reduce its economic and health burden. PMID- 27275191 TI - Serum Ceramide Kinase as a Biomarker of Cognitive Functions, and the Effect of Using Two Slimming Dietary Therapies in Obese Middle Aged Females. AB - AIM: Highlighting the impact of obesity on mental and cognitive functions using serum ceramide kinase enzyme concentration as a biomarker for cognitive evaluation in the middle aged females, and also targeting to control the obesity and simultaneously postponing the deterioration of the cognitive functions, by implementing two slimming dietary therapies each incorporating different functional ingredients known to boost cognition. SUBJECTS AND METHODS: Ninety six obese middle aged females, divided into two groups volunteered to follow a low caloric balanced diet combined with two bread supplements composed essentially of barley flour and wheat germ mixed with either 5% turmeric, group (A); or with 5% ginger, group (B) for 4 weeks, phase (1); to be followed by the hypocaloric diet alone for another 4 weeks, phase (2). RESULTS: By the end of phase (1), the biochemical analysis showed a positive response of the levels of C-peptide and modified homeostatic model assessment of insulin resistance; also increased levels of the serum ceramide kinase enzyme, coupled with improved cognitive functions tests. Improvement of the relevant metabolic profile, fasting blood glucose, blood pressure and the anthropometric measurements was detected. CONCLUSION: Using dietary therapy supported by special formulas which contain active ingredients succeeded in reducing weight and improving both the metabolic profile and the cognitive functions. PMID- 27275192 TI - Is Neck Circumference an Indicator for Metabolic Complication of Childhood Obesity? AB - BACKGROUND: The possible role of neck circumference (NC) for screening childhood obesity and its complication is not well characterized. AIM: To assess NC and to explore its increase as risk factor with metabolic syndrome (MS) variables. METHODS: Cross sectional case-control study included 50 obese children (BMI >=95(th) percentile) and 50 healthy (BMI 15(th)-<85(th) percentile). All were subjected to clinical examination, measuring blood pressure (BP), body weight, height, NC, waist (WC) and hip (HC)., fasting blood glucose, insulin and lipid profile. RESULTS: MS was detected among 52% of obese participants, but not among controls (0%). Clinical parameters and most of the laboratory values were higher in subjects with MS than in non-metabolic subjects, with statistical significance only in blood pressure and triglycerides. Among obese without MS, NC showed significantly positive correlations with age, weight, height, WC, HC and negative with LDL. While among Obese with MS, NC showed significantly positive correlations with age, weight, height, BMI-SDS, WC, HC and DBP. CONCLUSION: NC can be considered as a good indicator and predictor for obesity, especially central obesity. However, NC has no relation with lipid profile or fasting blood sugar. PMID- 27275193 TI - Determination of Acyclovir in Human Plasma Samples by HPLC Method with UV Detection: Application to Single-Dose Pharmacokinetic Study. AB - BACKGROUND: The aim of this study is estimation of pharmacokinetic parameters: Cmax, tmax, t1/2, AUC0-t and AUC0-infinity with the two-way analysis of variance, single observation (ANOVA) for two preparations containing acyclovir. OBJECTIVE: In order to evaluate pharmacokinetic study of acyclovir, method for quantitative determination of acyclovir in human plasma should be simple, rapid and reproducible. Therefore, the method is developed, validated and applied for analysis of acyclovir in plasma samples obtained from healthy volunteers. MATERIAL AND METHODS: High performance liquid chromatographic (HPLC) method with UV-detection for the determination of acyclovir in human plasma is presented. This method involves protein precipitation with 20 % (V/V) perchloric acid. The chromatographic separation was accomplished on a reversed phase C8 column with a mobile phase composed of 0.1 % (V/V) triethylamine in water (pH 2.5). No internal standard is required. UV detection was set at 255 nm. The method was successfully applied for the evaluation of pharmacokinetic profiles of acyclovir tablets in 24 healthy volunteers. RESULTS: The validation results shows that proposed method is rugged, precise (RSDs for intra- and inter-day precision ranged from 1.02 to 8.37 %) and accurate (relative errors are less than 6.66 %). The calibration curve was linear in the concentration range of 0.1-2.0 ug/ml and the limit of quantification was 0.1 ug/ml. The Cmax, tmax and AUCs for the two products were not statistically different (p>0.05), suggesting that the plasma profiles generated by Zovirax were comparable to those produced by acyclovir manufactured by Jaka 80 company. CONCLUSION: Good precision, accuracy, simplicity, sensitivity and shorter time of analysis of the method makes it particularly useful for processing of multiple samples in a limited period of time for pharmacokinetic study of acyclovir. PMID- 27275194 TI - Prediction of Gut Wall Integrity Loss in Viral Gastroenteritis by Non-Invasive Marker. AB - BACKGROUND: Intestinal fatty acid binding proteins (I-FABPs) are mainly expressed in the intestinal villi, which are the initial site of destruction in viral gastroenteritis. AIM: This study was designed to assess serum I-FABPs as a predictor of gut wall integrity loss in viral gastroenteritis. PATIENTS AND METHODS: This case-control cross-sectional study was conducted on 93 cases of acute viral gastroenteritis. Twenty-eight healthy children matching in age were recruited as control group. Serum I-FABPs were measured using ELISA technique. Viral detection and typing were done by PCR for adenovirus, and by Reverse transcriptase PCR for rotavirus, astrovirus and norovirus. RESULTS: Serum I-FABPs level was significantly higher in the cases compared to the controls and was also higher in the 46 rotavirus gastroenteritis cases compared to other viral gastroenteritis cases. Serum I- FABPs level was significantly higher in severely dehydrated cases as compared to mildly dehydrated ones (P=0.037). CONCLUSION: Serum I-FABPs could be used as an early and sensitive predictor marker of gut wall integrity loss in children with viral gastroenteritis and its level can indicate case severity. PMID- 27275195 TI - Some Adverse Effects of Used Engine Oil (Common Waste Pollutant) On Reproduction of Male Sprague Dawley Rats. AB - AIM: Used oil is contaminated not only with heavy metals but also with polycyclic aromatic hydrocarbons (PAHs) that are insignificant in the unused oil. In our study we determined possible reproductive effects of used engine oil on male rats. MATERIAL AND METHODS: Twenty eight male Wistar rats were used for the study. The rats had average weight of 181.5 +/- 10 g, animal feeds and portable water was provided ad-libitum. The rats were assigned to 4 groups (n = 7) including control. The treated groups orally received 0.1 ml/rat, 0.2 ml/rat and 0.4 ml/rat of the used engine oil every other day for 28 days using oral canulla. The spermatozoa were collected from epididymis for sperm analysis and testes were removed and preserved in Bouin's fluid for routine histological analysis. RESULTS: Our results showed that there was progressive weight increase among the control group of rats that received distilled water. Meanwhile, rats that received 0.4 ml/rat of the used engine oil showed significant (P < 0.05) weight loss in second and third week of administration while rats that received 0.2 ml/rat and 0.1 ml/rat of the used engine oil showed non-significant (P > 0.05) weight reduction. The spermatozoa number was decreased with significance (P < 0.05) at 0.2 ml/rat (2.38 +/- 0.29) and 0.4 ml/rat (1.98 +/- 0.08) when compared with the control (5.00 +/- 0.89). However, the percentage of motile sperms was reduced significantly (P <0.05) at 0.2 ml/rat (52.86 +/- 3.59) and 0.4 ml/rat (45.71 +/- 2.94) except at 0.1 ml/rat where the reduction (64.00 +/- 7.5) was not significant (P> 0.05). The percentage of head deformity been 41.43 +/- 2.61 and 42.00 +/- 3.74 at 0.2 ml/rat and 0.4 ml/rat respectively, also significant increase of middle piece deformity was observed only at 0.1 ml/rat (45.71 +/- 2.02) while tail deformity significantly decreased (15.71 +/- 2.02, 20.00 +/- 4.36 and 20.00 +/- 4.47) when compared with the control (30.00 +/- 1.29). The testicular seminiferous tubules were slightly degenerated with absence of Lumen. The germinal cell layer consisting of necrosis of spermatogonia and interstitial (Leydig) cells with affected Sertoli cells at different maturation stages. CONCLUSION: Hence, it can be said that there is a negative relation between used engine oil and male reproductive parameters. And it can be concluded that used engine oil should be prevented from leaking, spilling or improperly discarded as through medium it may enter storm water runoff and eventually affect the environmental health receiving water bodies. PMID- 27275196 TI - Investigation of Propolis' Effect on Thiobarbituric Acid Reactive Substances and Anti-Oxidant Enzyme Levels of Hippocampus in Diabetic Rats Induced by Streptozotocin. AB - BACKGROUND: Propolis is an organic resinous viscous substance collected from flower bud and plant sprig by bees. Propolis has a potential treatment agent for oxidative damage caused by diabetes in hippocampus due to its flavonoid and phenolic content. AIM: In this study effect of propolis on thiobarbituric acid reactive substances and anti-oxidative enzyme levels of hippocampus in diabetic rats induced by streptozotocin was investigated. MATERIALS AND METHODS: The study involved measuring levels of SOD, CAT, GSH-Px and TBARs in hippocampus tissue of STZ-induced diabetic rats (Adult Male Sprague Dawley rats) after applying propolis for one month. The subjects of the study were composed of 51 rats randomly assigned to four groups (Control, STZ, P+STZ and STZ+P). For analysis of data, Kruskal Wallis Test was utilized. RESULTS: The findings of the study showed that there were no significant difference in the levels of TBARS, SOD, CAT and GSH-Px of hippocampus across the groups. CONCLUSION: Propolis application in four week duration does not have effect on TBARS, SOD, CAT and GSH-Px levels of hippocampus of diabetic rats. These findings mean that more time for observing oxidative harms on hippocampus is needed. PMID- 27275197 TI - Preferentially Expressed Antigen of Melanoma (PRAME) and Wilms' Tumor 1 (WT 1) Genes Expression in Childhood Acute Lymphoblastic Leukemia, Prognostic Role and Correlation with Survival. AB - BACKGROUND: Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in children. In young children it is also largely curable, with more than 90% of afflicted children achieving long-term remission. PRAME (Preferentially expressed antigen of melanoma) gene belongs to Group 3 class I HLA-restricted widely expressed antigens in which genes encoding widely expressed tumor antigens have been detected in many normal tissues as well as in histologically different types of tumors with no preferential expression on a certain type of cancer. It has been found to be expressed in a variety of cancer cells as leukemia & lymphoma. PRAME monitoring can be useful for detection of minimal residual disease and subsequent relapses particularly those leukemias in which specific tumor markers are unavailable. Wilms' tumor1 (WT1) gene was identified as a gene that plays an important role in normal kidney development and inactivation of its function was shown to result in the development of Wilms' tumors in paediatric patients. Disruption of WT1 function has been implicated in the formation of many different tumor types. AIM: to study how PRAME & WT 1 genes expression patterns influence cancer susceptibility & prognosis. PATIENTS & METHODS: 50 patients with denovo childhood acute lymphoblastic leukemia, as well as 50 age and sex matched apparently healthy volunteers were genotyped for PRAME and WT1 genes expression by reverse transcription polymerase chain reaction (RT PCR). RESULTS: PRAME gene was expressed in 34 of the patients (68%) and WT1 gene was expressed in 26 of the patients (52%). Expression of both genes was significantly higher compared to controls (P < 0.0001). Analysis of relapse free survival among our patients revealed that patients expressing PRAME gene or WT1 gene had better relapse free survival (p value=0.02 and 0.01 respectively). Relapse free survival increased significantly among patients coexpressing PRAME and WT 1(p value =0.001). CONCLUSION: It is concluded that the expression of PRAME and WT1 genes are indicators of favorable prognosis and can be useful tools for monitoring minimal residual disease (MRD) in acute leukemia especially in patients without known genetic markers. Differential expression between acute leukemia patients and healthy volunteers suggests that the immunogenic antigens (PRAME and WT1) are potential candidates for immunotherapy in childhood acute leukemia. PMID- 27275198 TI - Early Zinc Supplementation and Enhanced Growth of the Low-Birth Weight Neonate. AB - BACKGROUND: Nutritional deficits are almost universal in Low-Birth Weight babies. Zinc is essential for normal infant growth and its supplementation assists growth probably through insulin-like growth factor-1. AIM: This double-blind randomized controlled trial aimed at evaluating the role of zinc in catch-up growth of low birth-weight infants and investigating its proposed mediator. MATERIAL AND METHODS: The study was conducted in Ain Shams University Maternity Hospital. Two hundred low-birth-weight neonates were simply randomized to either oral zinc therapy or placebo. Anthropometric measurements were recorded at birth, 3, 6, and 12 months; including weight, recumbent length, head, waist, chest, and mid-upper arm circumferences, and triceps and sub-scapular skin fold thickness. RESULTS: We found that initial and 3-months measurements, except weight, were comparable in the 2 groups. All measurements at 6- and 12-months, except sub-scapular skin-fold thickness, were significantly higher in zinc group than placebo. Catch-up growth, at 12-months, was significant in zinc group and was significantly higher in appropriate-for-gestational-age vs. small-for-gestational-age, in preterm vs. term, and in male vs. female infants. The median 6-months insulin-like growth factor-1 levels were significantly higher in zinc group. CONCLUSION: We conclude that early start of oral zinc supplementation in low-birth-weight neonates assists catch-up growth, probably through rise of insulin-like growth factor-1. PMID- 27275199 TI - Gender Associated High Body Mass Index in Allergic Diseases. AB - BACKGROUND: The increasing prevalence of allergic diseases and atopy is affected by sex, age and lifestyle factors. Obesity and excess weight are reported to be potential risk factors for atopy and specifically for asthma symptoms in children and adults. OBJECTIVE: To assess the relation between body mass index (BMI) and allergic diseases in patients of both genders, as well as association of BMI with atopy in healthy subjects. METHODS: BMI (kg/m(2)), skin-prick test and total serum immunoglobulin E levels were assessed in 139 subjects: 109 were patients with allergic diseases (M to F ratio was 51:58) and 30 were healthy controls (M to F ratio was 6:24). RESULTS: The study population was grouped into asthma, asthmarhinitis, rhinitis, Urticaria oreczema and controls by BMI and sex. Females with the highest BMI were in asthma and urticaria/eczema group. Males with the highest BMI were in asthmarhinitis and urticariaeczema group. High BMI was associated with atopy in both genders of healthy controls. High levels of total IgE were in male allergic patients. CONCLUSION: High BMI was associated with asthma in females, urticaria/eczema in both genders and atopy in both genders of healthy controls. Higher levels of total IgE were concluded in male patients. PMID- 27275200 TI - Prognostic Factors and Survival in Non-Small Cell Lung Cancer Patients Treated with Chemoradiotherapy. AB - BACKGROUND: According to the literature, performance status, stage-tumor dimension and nodal status, weight loss, were the most important prognostic factors for survival in patients with locally advanced non-small cell lung cancer. AIM: To evaluate the treatment results and the prognostic variables in our patients treated with sequential and concurrent chemoradiotherapy. MATERIAL AND METHODS: In the study 85 patients were randomly assigned to one of the two treatment arms. In the sequential arm, 45 patients had previously received sequential chemotherapy with 4 cycles of and etoposide followed by conformal radiotherapy (RT). In the second concurrent group, 40 patients received concomitant chemotherapy of cisplatine and etoposide and conformal RT, followed by two cycles of consolidation chemotherapy of carboplatine and etoposide. We described all phases of the conformal three dimensional (3-D) RT. RESULTS: From October 2005 to March 2008, 93 patients were enrolled. Eight patients were not eligible, seven had stage IV and one patient had pleural effusion. They were all initially considered to have stage IIIB disease. The median survival was 13 months for the patients in the sequential arm and 19 months for those in the concurrent treatment arm. The differences were statistically significant (log rank test p=0.0039). The disease-free survival was 9 months in the sequential arm and 16 months in the concurrent treatment group. The differences were statistically significant (log-rank test p=0.0023). We found that the following prognostic factors significantly influenced the survival in lung cancer patients treated with conservative method: - age, p<0.05; - performant status, p<0.001; - weight loss, p<0.001; tumor dimension, p<0.05; and - nodal involvement, p<0.05. CONCLUSION: In our study, the dose-limiting toxicity, esophagitis was reduced by performing conformal radiotherapy. Conformal thoracic radiotherapy and new radiotherapy technics, such as respiratory gated radiotherapy, allow dose escalating and may probably improve survival and local control in lung cancer patients. PMID- 27275201 TI - Association of Serum 25-Hydroxyvitamin D with Life Style and Dietary Factors in Egyptian Prepubescent Children. AB - BACKGROUND: There had been a growing evidence of high prevalence of vitamin D deficiency especially among children which may increase the risk of many chronic diseases in adulthood. AIM: Assessment of different lifestyles and dietary behaviour influencing the level of serum 25-OHD in a group of Egyptian prepubescent children. SUBJECTS AND METHODS: Two hundred boys and girls aged from 9 to 11 years were recruited from two primary public schools situated in Giza governorate in Egypt. A questionnaire was developed to obtain relevant information related to age, dietary habits, and physical activity. Thorough clinical examination and measurement of weight and height were performed. Body mass index was calculated. Serum samples were assayed for 25-hydroxy vitamin D (25-OHD). RESULTS: Low serum 25-OHD (< 20 ng/ml) was found in 11.5% of the whole sample. Mean serum 25-OHD was significantly lower in obese subjects and in those with low physical activity (p < 0.05). Multiple stepwise linear regression analysis showed that BMI and physical activity were the main predictors of serum 25-OHD (P < 0.05). CONCLUSIONS: Lifestyle factors in terms of physical activity and BMI may contribute significantly to the optimal vitamin D status of apparently healthy children. PMID- 27275202 TI - Effect of Acupuncture on Body Weight Reduction and Inflammatory Mediators in Egyptian Obese Patients. AB - AIM: Aim of this study was to examine the effectiveness of body acupuncture on body weight loss, routine laboratory tests and pro-inflammatory markers. METHODOLOGY: The study was performed on eighty obese patients. They were divided into three groups according to their body mass index. Subjects received acupuncture for three- six months in combination with a low-calorie diet. They were assessed pre and post acupuncture, by anthropometric measurement, routine laboratory tests and, tumor necrosis factor- alpha (TNF-alpha), interleukin- 6 (IL-6), and high sensitivity C-reactive protein (hsCRP) levels in serum. RESULTS: The pre-acupuncture results showed significant difference between the three grades of obesity and the controls regarding TNFalpha, IL-6 and hsCRP. We found significant reduction in anthropometric measurement of adiposity after acupuncture. In comparing the pre &post acupuncture results of TNF-alpha, IL-6 and hsCRP showed high significant reduction after acupuncture. There are highly significant decrease in kidney function (creatinine and uric acid) and lipid profile (cholesterol and triglycerides) and fasting blood glucose, but there was no significant difference in urea, SGPT, SGOT, HDL and LDL. CONCLUSION: Body acupuncture in combination with diet restriction was found to be effective for weight loss and also reduction of the inflammatory reactions. Acupuncture could be used as a synergistic treatment option for obesity control. PMID- 27275203 TI - Predictors of High Serum Casein Antibody Levels among Malnourished Infants and Young Children with Congenital Heart Disease. AB - BACKGROUND: Factors predictive of growth retardation and malnutrition in patients with congenital heart disease remain unclear. OBJECTIVES: This study aimed to measure antibody response to bovine casein through assessing serum casein antibody levels in malnourished patients three year or younger with CHD, and to determine its relationship to gastrointestinal symptoms, anthropometric measures, and laboratory data. SUBJECTS AND METHODS: This cross sectional case control study was conducted in sixty patients with CHD aged 4 to 72 months. They were subdivided into thirty patients with cyanotic and thirty patients with acyanotic CHD compared with thirty apparently healthy children. RESULTS: On comparison with controls, patients showed highly significant lower anthropometric measures, calcium, iron, hemoglobin levels, and higher serum levels of casein antibody, total iron binding capacity, and alkaline phoshatase activity (P<0.000). Serum levels of casein antibody showed significantly positive correlations with serum total iron binding capacity and alkaline phosphatase activities and negatively correlated with the age at onset of symptoms, anthropometric measures, serum calcium, and iron levels. CONCLUSION: Serum casein antibody levels play a significant role in the pathogenesis of malnutrition. Encouragement of breast feeding and avoidance of early cow's milk consumption could prevent the development of antibody response to bovine casein. PMID- 27275204 TI - Achieving Higher Diagnostic Results in Stereotactic Brain Biopsy by Simple and Novel Technique. AB - BACKGROUND: Neurosurgeons have preferred to perform the stereotactic biopsy for pathologic diagnosis when the intracranial pathology located eloquent areas and deep sites of the brain. AIM: To get a higher ratio of definite pathologic diagnosis during stereotactic biopsy and develop practical method. MATERIAL AND METHODS: We determined at least two different target points and two different trajectories to take brain biopsy during stereotactic biopsy. It is a different way from the conventional stereotactic biopsy method in which one point has been selected to take a biopsy. We separated our patients into two groups, group 1 (N=10), and group 2 (N= 19). We chose one target to take a biopsy in group 1, and two different targets and two different trajectories in group 2. In group 2, one patient underwent craniotomy due to hemorrhage at the site of the biopsy during tissue biting. However, none of the patients in both groups suffered any neurological complication related biopsy procedure. RESULTS: In group 1, two of 10 cases, and, in group 2, fourteen of 19 cases had positive biopsy harvesting. These results showed statistically significant difference between group 1 and group 2 (P<0.05). CONCLUSIONS: Regarding these results, choosing more than one trajectories and taking at least six specimens from each target provides higher diagnostic rate in stereotaxic biopsy taking method. PMID- 27275205 TI - Clinical Relevance of Transforming Growth Factor-beta1, Interleukin-6 and Haptoglobin for Prediction of Obesity Complications in Prepubertal Egyptian Children. AB - BACKGROUND: The rate of obesity is increasing throughout the world. Obesity in adults' research is characterized by chronic inflammation, associated with type 2 Diabetes and cardiovascular risk. The degree to which these changes occur in childhood obesity is not fully defined. AIM: This study was designed to explore the relation between circulating levels of pro-inflammatory cytokines, and obesity. PATIENTS AND METHODS: This cross sectional case control study was carried out in 50 randomly selected pre-pubertal overweight and obese children compared with fifty apparently healthy children of matched age and sex. Serum levels of transforming growth factor-beta1, interleukin-6, and haptoglobin were quantified by ELISA technique. RESULTS: ANOVA test followed by Post Hoc test showed highly significant increase in the serum levels of the transforming growth factor-beta1, interleukin-6 and haptoglobin among obese children compared to overweight and healthy children respectively. The body weight, BMI and BMI z score were significantly positively correlated with serum levels of the three pro inflammatory cytokines. Serum levels of interleukin-6, and haptoglobin were found to be strong predictors of complications in severe obesity by linear regression analysis. CONCLUSIONS: Obesity is associated with chronic low-grade inflammation. High levels of interleukin-6 and haptoglobin are considered to be early biomarkers of inflammation associated with severe obesity with subsequent cardiovascular and type 2 diabetes risk. PMID- 27275206 TI - Correlation of the CT Compatible Stereotaxic Craniotomy with MRI Scans of the Patients for Removing Cranial Lesions Located Eloquent Areas and Deep Sites of Brain. AB - The first goal in neurosurgery is to protect neural function as long as it is possible. Moreover, while protecting the neural function, a neurosurgeon should extract the maximum amount of tumoral tissue from the tumour region of the brain. So neurosurgery and technological advancement go hand in hand to realize this goal. Using of CT compatible stereotaxy for removing a cranial tumour is to be commended as a cornerstone of these technological advancements. Following CT compatible stereotaxic system applications in neurosurgery, different techniques have taken place in neurosurgical practice. These techniques are magnetic resonance imaging (MRI), MRI compatible stereotaxis, frameless stereotaxy, volumetric stereotaxy, functional MRI, diffusion tensor (DT) imaging techniques (tractography of the white matter), intraoperative MRI and neuronavigation systems. However, to use all of this equipment having these technologies would be impossible because of economic reasons. However, when we correlated this technique with MRI scans of the patients with CT compatible stereotaxy scans, it is possible to provide gross total resection and protect and improve patients' neural functions. PMID- 27275207 TI - Significance of Serum Cytokeratin-18 in Prediction of Hepatocellular Carcinoma in Chronic Hepatitis C Infected Egyptian Patients. AB - BACKGROUND: Hepatitis C virus is one of the most common etiologic agents of chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma in which there is continuous inflammation and regeneration of hepatocytes. Cytokeratin-18 (CK18) has been suggested to play an important role in tumorigenesis of epithelial cancers. AIM: Estimation of CK18 serum levels in patients with chronic viral hepatitis C (CHCV) and hepatocellular carcinoma (HCC) and find the relationship between their levels, the severity of the disease and the development of HCC. METHODS: We measured serum levels of CK18 in 60 Egyptian patients (30 with CHCV & 30 with HCC) and 30 healthy controls. RESULTS: Patients with HCC had highly significant increased CK18 levels compared with CHCV patients, healthy controls. Cytokeratin-18 among the three classes of Child-Pugh classification show highly significant gradual increase from child A to C. Furthermore, In HCC there were positive correlations between CK18 and with RBCs, ESR, and AFP. CONCLUSION: CK18 is a sensitive indicator of the severity of liver disease. Patients with CHCV infection can be followed up by measurement of its serum level which can predict the development of HCC. The combination of AFP and CK18 increased the sensitivity of detection for HCC. PMID- 27275208 TI - Association between Serum Cortisol and DHEA-S Levels and Response to Antipsychotic Treatment in Schizophrenia. AB - BACKGROUND: Previous studies suggested that alterations in serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia. AIM: To compare serum cortisol and DHEA-S levels between patients with schizophrenia and healthy controls and to evaluate their association with the response to antipsychotic treatment. MATERIAL AND METHODS: In this clinical prospective study were included 60 patients with schizophrenia and 40 healthy age and sex matched control subjects. Clinical evaluation of patients was performed using the Positive and Negative Symptom Scale. A questionnaire for socio-demographic and clinical data collection was used. For the purposes of the study, the examined group was divided in two subgroups: responders and nonresponders. Serum cortisol and DHEA-S levels were measured at baseline in all participants and after 3 and 6 weeks of the antipsychotic treatment in patients with schizophrenia. RESULTS: Patients with schizophrenia had significantly higher serum cortisol and DHEA-S levels in comparison to the control group. Responders had significantly higher serum cortisol and DHEA-S levels compared with nonresponders. CONCLUSION: Elevated serum cortisol and DHEA-S levels may play a role in the pathophysiology of schizophrenia and they may be related to positive response to antipsychotic treatment in patients with schizophrenia. PMID- 27275209 TI - Klippel - Feil Syndrome Associated with Congential Heart Disease Presentaion of Cases and a Review of the Curent Literature. AB - First time described in 1912, from Maurice Klippel and Andre Feil independently, Klippel-Feil syndrome (synonyms: cervical vertebra fusion syndrome, Klippel-Feil deformity, Klippel-Feil sequence disorder) is a bone disorder characterized by the abnormal joining (fusion) of two or more spinal bones in the neck (cervical vertebrae), which is present from birth. Three major features result from this abnormality: a short neck, a limited range of motion in the neck, and a low hairline at the back of the head. Most affected people have one or two of these characteristic features. Less than half of all individuals with Klippel-Feil syndrome have all three classic features of this condition. Since first classification from Feil in three categories (I - III) other classification systems have been advocated to describe the anomalies, predict the potential problems, and guide treatment decisions. Patients with Klippel-Feil syndrome usually present with the disease during childhood, but may present later in life. The challenge to the clinician is to recognize the associated anomalies that can occur with Klippel-Feil syndrome and to perform the appropriate workup for diagnosis. PMID- 27275210 TI - Cervicothoracic Arachnoid Cyst Causing Cervical Myelopathy: A Case Report. AB - Several types of intraspinal cyst develop within the spinal canal from the craniovertebral junction to the sacrum. These lesions occur in both children and adults. Arachnoid cysts are one of them and are more frequent in the paediatric population, being a relatively uncommon lesion in adults. The arachnoid cyst may be located intradurally or extradurally. The intradural type may be congenital or from spinal trauma, infection or spondylosis. Although intradural arachnoid cysts are often asymptomatic, they may give early symptoms when they exist with synchronous pathologies constricting the spinal canal gradually as in cervical spondylosis. In this report, a 60-year-old man with an arachnoid cyst of the cervicothoracic spine is presented. His cyst remained undiagnosed because of the nonspecific nature of the symptoms. It was only when he developed right hemiparesis that a posterior fluid collection compressing the spinal cord was found in Magnetic resonance imaginig. An intradural extramedullary cyst was removed with successful surgery and cord compression and symptoms were reversed. We discuss radiological diagnosis and surgical treatment of an arachnoid cyst in this report. PMID- 27275211 TI - Internal Mammary Sentinel Lymph Nodes in Breast Cancer - Effects on Disease Prognosis and Therapeutic Protocols - A Case Report. AB - BACKGROUND: The main prognostic factor in early staged breast cancer is the axillary lymph node metastatic affection. Sentinel lymph node biopsy, as a staging modality, significantly decreases surgical morbidity. The status of internal mammary lymph nodes gains an increased predictive role in grading breast carcinomas and modulation of postoperative therapeutic protocols. If positive, almost always are associated with worse disease outcome. Nevertheless, the clinical significance of internal mammary lymph node micrometastases has not been up to date precisely defined. AIM: To present a case of female patient clinically diagnosed as T1, N0, M0 (clinical TNM) ductal breast carcinoma with scintigraphic detection of internal mammary and axillary sentinel lymph nodes. METHODS: Dual method of scintigraphic sentinel lymph node detection using 99mTc-SENTI-SCINT and blue dye injection, intraoperative gamma probe detection, radioguided surgery and intraoperative ex tempore biopsy were used. CASE REPORT: We present a case of clinically T1, N0, M0 ductal breast cancer with scintigraphic detection of internal mammary and axillary sentinel lymph nodes. Intraoperative ex tempore biopsy revealed micrometastases in the internal mammary node and no metastatic involvement of the axillary sentinel lymph node. CONCLUSION: Detection of internal mammary lymph node metastases improves N (nodal) grading of breast cancer by selecting a high risk subgroup of patients that require adjuvant hormone therapy, chemotherapy and/or radiotherapy. PMID- 27275212 TI - Symptomatic Pneumocephalus after Lumbar Disc Surgery: a Case Report. AB - Symptomatic pneumocephalus is frequently seen after traumatic fracture of the skull base bone. However, it has rarely been reported after spinal surgery and its mechanism has not been fully explained. In this paper, we present a 30 year old male patient who had lumbar discectomy due to a symptomatic midline lumbar disc herniation. He had developed symptomatic pneumocephalus after the lumbar disc surgery associated with application of a vacuum suction device. We present and discuss our patient in the light of the literatures. PMID- 27275213 TI - Work-Related Upper Limb Disorders: A Case Report. AB - In this study the complex interrelationship between physical factors, job stress, lifestyle and genetic factors on symptoms of work-related musculoskeletal disorders of the upper limbs is demonstrated by a case report and discussion of the literature. A 58 year old woman with long lasting complaints of the upper limbs with increasing intensity and duration, generalisation, combined with skin thickness, Raynaud's phenomenon, joint disorders, arterial and pulmonary hypertension, metabolic lipid dysfunctions is presented. Occupational history proves continuous duration of service at a job with occupational physical static load with numerous repetitive monotonous systematic motions of fingers and hands as a weaver of Persian rugs followed by work at an automated loom and variable labour activities. Though the complaints dated since the time she was a manual weaver, the manifestations of generalized joint degenerative changes, system sclerosis with Raynaud's phenomenon with similar upper extremities signs and symptoms discount upper limbs musculoskeletal disorder as caused only or mainly by occupational risk factors. The main principles and criteria for occupational diagnosis of musculoskeletal upper limb disorders and legislative requirements for their reglamentation are discussed. PMID- 27275214 TI - Use of Medicines from the Group of Benzodiazepines in the Period of 2003-2013 Year in the Republic of Macedonia. AB - AIM: The aim of this study was to analyze the use of benzodiazepines in the period of 2003-2013 year in the Republic of Macedonia (MKD). METHOD: The study was cross sectional and analyzes the available data on the use of benzodiazepines in the country. This study used several sources of data: Statistical Reports of the United Nations regarding the consumption of psychotropic substances; data from the Ministry of Health associated with the use of benzodiazepines (BZD), derived from reports of Ministry of Health stakeholders; Data extracted from the database of the Ministry of Health in the electronic database "My term" and Analysis of reports of Health Insurance Fund. RESULTS: The analysis for the period 2003-2013 showed that the most consumed drug in MKD from the group of BZD is Diazepam, with 54.8 and predominantly is use of diazepam of 5 mg with 59 %. According to the Health Insurance Fund, Diazepam is second most prescribed medicaments of all medicaments with marketing authorization in MKD. CONCLUSIONS: The analysis shows that the use of BZD in MKD is particularly high. Limited number of studies was performed for this kind of drugs relating to their effects; differences in use between genders; adult population. There is need for additional focused research that will contribute to developing a full picture of the situation. PMID- 27275215 TI - Chronic Respiratory Symptoms and Lung Function in Agricultural Workers - Influence of Exposure Duration and Smoking. AB - INTRODUCTION: Job exposure in agricultural workers often leads to respiratory impairment. AIM: To assess the influence of exposure duration and smoking on chronic respiratory symptoms and ventilatory capacity in agricultural workers. METHODS: A cross-sectional study covered 75 agricultural workers, compared with an equal number of office workers matched by age, exposure duration and smoking status. Standardized questionnaire was used to obtain data on chronic respiratory symptoms, job and smoking history. Lung functional testing was performed by spirometry. RESULTS: The prevalence of respiratory symptoms was higher in agricultural workers, with significant difference for cough (P = 0.034), and dyspnea (P = 0.028). Chronic respiratory symptoms among agricultural workers were significantly associated with duration of exposure (P < 0.05) and daily smoking (P < 0.01), as well as with daily smoking in controls (P < 0.01). The average values of spirometric parameters in exposed workers were significantly different for MEF50 (P = 0.002), MEF75 (P = 0.000), and MEF25-75 (P = 0.049). Obstructive changes in small airways in exposed workers were strongly related to exposure duration (P < 0.05) and smoking (P < 0.01). Agricultural workers with job exposure more than 15 years had more expressed adverse respiratory symptoms and lung function decline. CONCLUSION: The results confirmed the influence of agricultural exposure and daily smoking on chronic respiratory symptoms and airflow limitation, primarily targeting the small airways. PMID- 27275216 TI - Burnout and Work Demands Predict Reduced Job Satisfaction in Health Professionals Working In a Surgery Clinic. AB - BACKGROUND: Burnout syndrome develops in health professionals (HPs) as a result of exposure to chronic emotional and interpersonal workplace stressors. Research demonstrates the links between burnout, work demands, and job satisfaction in hospital HPs. AIMS: To examine the associations between burnout, work demands and job satisfaction, and to demonstrate the mediation effect of emotional exhaustion on the relationship between work demands and job satisfaction in surgery clinic HPs. METHODS: Maslach Burnout Inventory was used for assessment of burnout. Work demands and job satisfaction were measured with Hospital Experience Scale and Job Satisfaction Survey, respectively. In order to examine the role of emotional exhaustion, depersonalization, and work demands, controlling for age, hospital tenure, and unit tenure, a hierarchical multiple regression models were tested for each job satisfaction factor. RESULTS: Job satisfaction was negatively predicted by emotional exhaustion. Certain types of work demands negatively predicted different factors of job satisfaction. Emotional exhaustion was a significant partial mediator of the relationship between work demands and job satisfaction. CONCLUSIONS: Adequate management of work demands, particularly excessive workload, time pressure, and lack of staff can lead to prevention of burnout and reduced job satisfaction in surgery clinic HPs, and contribute to better quality of patient care. PMID- 27275217 TI - Ebola in West Africa. AB - Ebola viral disease (EVD) is a severe and life-threatening disease. The current Ebola outbreak in West Africa entered its second year and is unprecedented because it is the largest one in history, involved urban centers and affected a large number of health care workers. It quickly escalated from medical into a humanitarian, social, economic, and security crisis. The primary pillars to prevent EVD are: early diagnosis, isolation of patients, contact tracing and monitoring, safe burials, infection prevention and control and social mobilization. The implementation of all these components was challenged in the field. Key lessons from this Ebola outbreak are that countries with weak health care systems can't withstand the major outbreaks; preparedness to treat the first confirmed cases is a national emergency; all control measures must be coordinated together and community engagement is the great factor to combat this disease. PMID- 27275218 TI - Work Demands-Burnout and Job Engagement-Job Satisfaction Relationships: Teamwork as a Mediator and Moderator. AB - BACKGROUND: Few studies have examined teamwork as mediator and moderator of work demands-burnout and job engagement-job satisfaction relationships in healthcare workers (HCWs) in South-East Europe. AIM: To assess mediation and moderation effect of teamwork on the relationship between independent (work demands or job engagement) and dependent (burnout or job satisfaction) variables. METHODS: Work demands, burnout, job engagement, and job satisfaction were measured with Hospital Experience Scale, Maslach Burnout Inventory, Utrecht Work Engagement Scale, and Job Satisfaction Survey, respectively. Hospital Survey on Patient Safety Culture was used for assessment of teamwork. In order to examine role of teamwork as a mediating variable we fit series of regression models for burnout and job satisfaction. We also fit regression models predicting outcome (burnout or job satisfaction) from predictor (work demands or job engagement) and moderator (teamwork) variable. RESULTS: Teamwork was partial mediator of work demands-burnout relationship and full mediator of job engagement-job satisfaction relationship. We found that only job engagement-job satisfaction relationship was moderated by teamwork. CONCLUSIONS: Occupational health services should target detection of burnout in HCWs and implementation of organizational interventions in hospitals, taking into account findings that teamwork predicted reduced burnout and higher job satisfaction. PMID- 27275219 TI - Association between Macronutrients Intake, Visceral Obesity and Blood Pressure in a Sample of Obese Egyptian Women. AB - AIM: Study the association between the total caloric intake, protein, lipid, and some classes of fatty acids of the diet, and their effects on blood pressure in a sample of Egyptian obese women with and without visceral obesity. METHODS: Five hundred forty-nine obese women were included in the study with mean age of 38.1 +/- 11.56 years and mean Body mass index [BMI] of 36.17 +/- 7.23. They enrolled in a program for losing weight. Visceral fat was determined using ultrasound. Blood pressure was measured 3 times and the mean was recorded. Twenty four hours dietary recall was reported. RESULTS: Thirty point four percentages of samples has visceral obesity >= 7cm; they were the older, showed higher values of BMI, visceral obesity and blood pressure. Significant difference was found between groups regarding mean value of BMI, visceral obesity, both systolic blood pressure SBP and diastolic blood pressure DBP and most of the daily macronutrients intake. In groups (2&3) positive significant correlation was recorded between (SBP) & (DBP) and total daily intake of total calories, carbohydrate, total fat, saturated fatty acids and cholesterol, and negative significant correlation with total daily intake of total protein, animal and vegetable protein, linolenic and linoleic fatty acids, while oleic fatty acid showed negative correlation with SBP&DBP in all groups. CONCLUSION: This study emphasizes the hypothesis that the macronutrients composition of diet influences blood pressure in different ways, in obese patients with visceral obesity. PMID- 27275220 TI - Statistical Study of Risk Factors of End Stage Renal Failure in Peshawar, Pakistan. AB - BACKGROUND: End Stage Renal Failure (ESRD) is the last stage of the chronic renal failure in which kidneys become completely fail to function. AIM: The basic aim of this study was to discover the important risk factors of ESRD and to construct a model for prediction of the ESRD patients in various hospitals of Peshawar, Pakistan. MATERIAL AND METHODS: The data were collected from the patients of renal diseases from three major hospitals of Peshawar. Brown method was used to obtain initial model, then backward elimination logistic regression analysis was performed to find the significant variables (risk factors). The response variable (ESRD) in this study is binary; therefore, logistic regression analysis is used to identify the significant variables. A Statistical Package GLIM and SPSS were used for fitting the model and for finding the significant variables. RESULTS: The backward elimination procedure selects predictor variables diabetic, hypertension, glomerulonephritis and heredity, for males. Thus, these variables are the main causes of ESRD. For females, the predictor variables selected are hypertension & (Diabetic*Hypertension), which means that hypertension and hypertensive diabetic are significant causes of ESRD. CONCLUSION: Our main conclusion from this analysis is that diabetic, hypertension and glomerulonephritis are the significant risk factors of ESRD. PMID- 27275221 TI - Lactoferrin Enhanced Apoptosis and Protected Against Thioacetamide-Induced Liver Fibrosis in Rats. AB - BACKGROUND: Liver fibrosis is the common pathologic consequence of all chronic liver diseases. AIM: Lactoferrin (Lf) was investigated for its possible hepatoprotective effect against thioacetamide (TAA)-induced liver fibrosis rat model. MATERIAL AND METHODS: Rats received TAA (200 mg/kg/biweekly, ip) for four successive weeks. Lf (200 mg/kg/day, p.o.) or vehicle (VHC) was administered for one month before and another month during TAA injection. Body weight and mortality rate were assessed during the month of TAA-intoxication. Thereafter, serum and liver tissues were analyzed for liver function, oxidative, fibrotic and apoptotic markers. RESULTS: Lf conserved rats against TAA-induced body weight loss and mortality. Preservation of serum albumin, alkaline phosphatase and total bilirubin levels was also observed. Lf also protected rats against TAA-induced decrease in reduced glutathione and increase in malondialdehyde liver contents. Normal liver contents of hydroxyproline, nuclear factor kappa B and alpha fetoprotein; as markers of fibrosis; were increased with TAA and conserved with Lf-TAA. Lf maintained the normal architecture of the liver and immunohistochemical findings revealed increase in apoptotic bodies compared to TAA that favored necrosis. CONCLUSION: In conclusion, Lf improved liver function, reduced oxidative stress and liver fibrosis, and enhanced apoptosis in rats with liver fibrosis, suggesting it to have useful therapeutic potential in patients with liver fibrosis. PMID- 27275222 TI - Total IgE Distribution in Food Allergy Suspected Patients in Republic of Macedonia (2001-2011). AB - BACKGROUND: IgE may be considered the hallmark of allergic disorders. It is easily detected in serum and can be measured as total IgE and as allergen specific IgE. In fact, the serum IgE assay is used to diagnose an allergy. AIM: The aim of this study is to evaluate, investigate and present the distribution of total serum IgE levels, determined with UniCap system, in food-allergy suspected patients in a Republic of Macedonia. MATERIAL AND METHODS: In this study we analyzed retrospectively 8898 consecutive patients that were admitted for allergy testing at the Institute of Immunobiology and Human Genetics during the ten year period between 01.01.2001 and 01.01.2011. Total IgE levels in patient sera were detected with the in vitro system UniCAP100 (Pharmacia, Uppsala, Sweden). RESULTS: When we analyzed the number of patients according to the total IgE groups, we noted that most of the patients have normal levels of total IgE in serum. However, we also discovered a group of patients with elevated levels of total IgE that are greater than 200 kU/L. The average concentration of total serum IgE is higher in women in the age group 6 (6-7 years), followed by a steep decrease in the age group 9 (9-10 years), and after that the average concentrations of total IgE were mostly constant with the exception of a partial increase in the age group 21 (65-69 years). For men, the average serum concentrations of total IgE were highest in the age group of 6 (6-7 years), which was significantly higher than the average concentrations of total IgE in all other age groups. CONCLUSION: The large number of enrolled patients, a particular strength of this study, revealed that average concentrations of total IgE in men are higher than in women and that total IgE did not decrease with age. On the contrary, increased total IgE levels were found in patients aged 65 and 69 of both genders. We continue our work with analyses of the specific IgE antibodies values toward food and the correlation with total IgE values. PMID- 27275223 TI - Tumor-Associated Macrophage (TAM) and Angiogenesis in Human Colon Carcinoma. AB - AIM: This study aimed to clarify how macrophages affect prognosis in cancer colon and their association with tumor angiogenesis. MATERIAL AND METHODS: Forty four biopsies of colon carcinoma and 15 of benign adenomatous polyps were investigated for macrophages infiltration and microvessels density using immunohistochemistry and image morphometric analysis. Macrophages and blood vessels were stained immunohistochemically by CD68 and F-VIII markers respectively. The morphometric analysis was carried out on the immunohistochemically stained slides using the Leica Qwin 500 Image Analyzer. Both of macrophages infiltration and microvessels density were correlated with histological tumor grade, stage and lymph node metastases and were correlated with each others. RESULTS: Macrophage infiltration was significantly higher in malignant cases than in benign polyps. High macrophage infiltration and hypervascularity were significantly correlated with T staging and lymph nodes metastasis. A significant correlation was found between macrophage infiltration and microvessels densitie in malignant tumors where hypervascularity was significantly correlated with high macrophages infiltration. CONCLUSION: The significant correlation between macrophage infiltration and tumor angiogenesis suggests an interaction between macrophages and cancer cells stimulating microvessels formation, tumor invasion and metastasis in colon cancer. We recommend that macrophages infiltration should be evaluated to investigate their clinical value in development of individualized therapeutic regimens for management of colon carcinoma. PMID- 27275224 TI - The Effect of the PEEK Cage on the Cervical Lordosis in Patients Undergoing Anterior Cervical Discectomy. AB - BACKGROUND: Loss of cervical lordosis is a significant factor in the development of degeneration of the spine with aging. This degenerative changings of the cervical spine would cause pressure effect on the cervical root and/or medulla spinalis. AIM: Our goal is to understand the effect of the PEEK cage on cervical lordosis in the early postoperative period. Also, to interpret the effects of one level, two- level, three-level and four- level disc pathologies on cervical lordosis. MATERIAL AND METHODS: We retrospectively investigated our archive, and we selected thirty-four patients undergoing anterior cervical discectomy and fusion with PEEK cage filled with demineralized bone matrix (ACDFP). RESULTS: We determined that ACDFP provides improvement in the cervical lordosis angle in both groups. Also, we found statistically significant difference between group 1 and 2 regarding causes of radiculomyelopathy statistically. CONCLUSION: We achieved better cervical lordotic angles at the postoperative period by implanting one level, two-level, three-level or four-level PEEK cage filled with demineralized bone matrix. Also, the causes of cervical root and or medulla spinalis impingement were different in group1 and 2. While extruded cervical disc impingement was the first pathology in group 1, osteophyte formation was the first pathology in group 2. PMID- 27275225 TI - The Accuracy of Noninvasive Imaging Techniques in Diagnosis of Carotid Plaque Morphology. AB - BACKGROUND: The stroke is leading cause of death and severe disability worldwide. Atherosclerosis is responsible for over 30% of all ischemic strokes. It has been recently discovered that plaque morphology may help predict the clinical behavior of carotid atherosclerosis and determine the risk of stroke. The noninvasive imaging techniques have been developed to evaluate the vascular wall in an attempt to identify "vulnerable plaques". AIM: The purpose is to investigate the diagnostic accuracy of ultrasound, multidetector computed tomography and magnetic resonance imaging in the identification of plaque components associated with plaque vulnerability. MATERIAL AND METHODS: One hundred patients were admitted for carotid endarterectomy for high grade carotid stenosis. We defined the diagnostic value of B-mode ultrasound of carotid plaque in a half, and the accuracy of multidetector computed tomography and magnetic resonance imaging, in the other group, for detection of unstable carotid plaque. The reference standard was histology. RESULTS: Sensitivity of ultrasound, multidetector computed tomography and magnetic resonance imaging is 94%, 83% and 100%, and the specificity is 93%, 73% and 89% for detection of unstable carotid plaque. CONCLUSION: The ultrasound has high accuracy for diagnostics of carotid plaque morphology, magnetic resonance imaging has high potential for tissue differentiation and multidetector computed tomography determines precisely degree of stenosis and presence of ulceration and calcifications. The three noninvasive imaging modalities are complementary for optimal evaluation of the morphology of carotid plaque. This will help to determine the risk of stroke and to decide on the best treatment - carotid endarterectomy or carotid stenting. PMID- 27275226 TI - Detection of BCR/ABL Translocation in Bone Marrow Derived Mesenchymal Stem Cells in Egyptian CML Patients. AB - BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. It is characterized at the cytogenetic level by Philadelphia (ph) chromosome and at the molecular level by the BCR/ABL gene rearrangement. Bone marrow derived mesenchymal stem cells (MSCs) are pluripotent stem cells that can differentiate into several mesenchymal tissues. AIM: To observe the biological characteristics of MSCS from CML patients and to determine whether MSCs harbor the abnormal BCR/ABL translocation similar to CML bone marrow cells. SUBJECTS AND METHODS: Characterized MSCs were isolated from 12 newly diagnosed Philadelphia positive untreated CML patients. RESULTS: MSCs can be readily isolated from CML marrow and exhibit major expansion. Flow cytometry analysis revealed the typical MSC phenotype. Moreover; MSCs do not harbor the BCR/ABL translocation confirmed by karyotype and real time PCR. CONCLUSION: MSCs from CML patients express the typical MSC phenotype; and do not express the BCR/ABL gene. Since; MSCs are able to support engraftment of hematopoietic stem cells in stem cell transplantation(SCT) as well as suppress alloreactive T cells causing graft versus -host disease, this current study provides evidence that in a SCT setting of CML patients, autologous MSCs could be a source of stem cell support in future cell therapy applications. PMID- 27275227 TI - Prelabour Rupture of Membranes: Mode of Delivery and Outcome. AB - BACKGROUND: Pre-labour Rupture of Membranes (PROM) is an important cause of maternal and fetal morbidity and increased rate of cesarean section delivery. AIM: The aim of this study is to investigate the clinical characteristics, PROM delivery interval, mode of delivery, and early maternal neonatal outcome among pregnant patients presenting with pre-labour rupture of membranes. MATERIAL AND METHODS: This prospective case control study is implemented at the Obstetric and Gynecology Clinic of the University Clinical Center of Kosovo. The study included 100 pregnant patients presenting with prelabour rupture of membranes of which 63 were primigravida and 37 patients were multigravida. RESULTS: The incidence of cesarean section in this study is 28 % and the most common indications for cesarean delivery were fetal distress, malpresentation, cephalopelvic disproportion, and failed induction. The most common maternal complications in this study are chorioamnionitis, retained placenta and postpartum hemorrhage. Neonatal infectious morbidity was present in 16 % of cases. CONCLUSION: PROM is a significant issue for obstetricians and an important cause of maternal and neonatal morbidity and increased rate of cesarean section delivery. PMID- 27275228 TI - Incidence of A-V Fistulas after Renal Biopsy of Native and Transplanted Kidney - Two Centers Experience. AB - AIM: The aim of the study is to make a retrospective analysis of the incidence of AV fistulas after renal biopsy (RB) of native and transplanted kidney. MATERIALS AND METHODS: Five hundred and sixteen (516) RB were analyzed. One hundred twenty nine (129) were native kidneys RB performed in Clinic of Nephrology (CN), 190 were performed in Clinic of Nephrology and transplantation (CNT) and 197 were transplanted kidney biopsies from the same clinic. Biopsy technique type Gun with needle 14G, 16 and 18 G was used in CN, CNT used the same technique with needles 16G. Doppler ultrasound was made for A-V fistulas diagnosis. RESULTS: The A-V fistulas incidence was 0.8%. The frequency of A-V fistulas registered in CN was significantly higher than that registered in CNT (2.3% vs. 0.5%, p < 0.01). Biopsies performed by 14 G needles provide a higher percentage of A-V fistulas compared to those done by 16 G. (3.3% vs. 2.4%, p < 0.5). The frequency of the A V fistulas in native and transplanted kidneys in CNT was similar (0.5% vs. 0.5%, p > 0.05). CONCLUSION: The A-V fistulas incidence is very low. The needle thickness is an important factor relevant to the risk of occurrence of A-V fistulas. PMID- 27275229 TI - Interactive Effects of Immunoglobulin Gamma and Human Leucocyte Antigen Genotypes on Response to Interferon Based Therapy of Hepatitis C Virus. AB - AIM: We examined the role that immunoglobulin GM 23 and KM allotypes-genetic markers of gamma and kappa chains, respectively-play in response to treatment of hepatitis C virus (HCV) infection in Egyptian patients. MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA -C genotyping was also done. RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001). Individuals who lacked this GM genotype (but were positive for KM1,2 and 3) were likely to respond to treatment (P=0.045). Association of heterozygous GM23 (+/-) with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001) and (P = 0.0001) respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027) while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001). The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001) and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003) while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001). CONCLUSION: Our results didn't support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies. PMID- 27275230 TI - IDH1 Mutation in Gliomas in Mosul City - Iraq. AB - BACKGROUND: IDH1 (isocitrate dehydrogenase 1) mutation might be encounter in the low grade glioma and directs the progression of the tumor to a higher grade. OBJECTIVE: To assess the frequency of IDH1 mutations in gliomas and to correlate the IDH1 positivity with the type and grade of tumors, the age and sex of the patients. MATERIAL AND METHODS: A retro- and prospective case series study. One hundred and nine cases of intracranial gliomas were collected between 2008 and 2014 from Mosul Private Laboratories and Al-Jamboree Teaching Hospitals in Mosul. IDH1 mutations were assessed immunohistochemically using anti-IDH1 R132H mouse monoclonal antibody. RESULTS: IDH1 mutation was perceived in 34.86% of gliomas. In adult gliomas, the secondary glioblastoma and the low-grade astrocytoma had the greatest values of IDH1 positivity (88.88% and 62.5% respectively), followed by oligoastrocytoma/oligodendroglioma (50.0%), and anaplastic astrocytoma (47.36%). The primary glioblastomsa showed 17.64% IDH1 positivity. Males and females expressed the IDH1 equally. While, there was no role of IDH1 in pediatric gliomas. CONCLUSION: IDH1 mutation is commonly present in adult gliomas particularly in low-grade gliomas, and secondary glioblastoma, with equal sex distribution, but it has no role in pediatric gliomas. PMID- 27275231 TI - Vitamin D Status in Patients with Systemic Lupus Erythematosus in Serbia: Correlation with Disease Activity and Clinical Manifestations. AB - BACKGROUND: Numerous studies indicate potential role of vitamin D as an important factor in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). Patients with SLE are especially prone to the development of vitamin D deficiency due to the nature of their illness. AIM: The aims of our study were to determine the prevalence of vitamin D insufficiency and deficiency in patients with SLE in Serbia, to identify clinical variables associated with vitamin D status and to examine the impact of vitamin D status on disease activity and presence of specific lupus autoantibodies. MATERIAL AND METHODS: The study included 46 patients with SLE. Serum 25(OH)D concentration was measured by electrohemiluminiscent immunoassay. RESULTS: The mean serum concentration of 25(OH)D was 11.9 +/- 7.3 ng/ml. The prevalence of insufficiency was 32.6%, while the prevalence of deficiency was 67.4%. There was no association between vitamin D status and photosensitivity, skin lesions, arthritis and lupus nephritis. Vitamin D status was not associated with the presence of specific autoantibodies. There was no correlation between disease activity assessed by SLEDAI scale with the concentration of 25(OH)D. Patients who used vitamin D supplements and calcium did not have a significantly higher concentration of 25(OH)D. CONCLUSION: In conclusion, vitamin D deficiency is common in patients with SLE. PMID- 27275232 TI - Dietary Patterns of Children with Autism Spectrum Disorder: A Study Based in Egypt. AB - AIM: In the hope to assist in tailoring individualized nutritional therapy, this study aimed to assess the nutritional status of autistic children. MATERIAL AND METHODS: This cross-sectional study included 80 autistic children, divided into two groups: group 1 (aged 3- 5 years) and group 2 (aged 6-9 years). Diagnosis was performed based on the criteria for autistic disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Autism Diagnostic Interview Revised and Autism Rating Scale. RESULTS: Socio-demographic data, anthropometric measurements and dietary intake patterns were recorded using a validated questionnaire. The daily intakes of calories and nutrients were converted to percentages of the Recommended Dietary Allowance or Dietary Reference Intake based on age- and gender-normalized DRIs. Plotting on the Egyptian sex-specific growth chart, BMI-z scores of both age groups were slightly overweight. Autistic children suffered inadequate intake of some micronutrients such as vitamin D and C, calcium, folate, magnesium, phosphorus, zinc, and iron, some deficiencies were highly significant especially at older age. CONCLUSIONS: Tailoring a specially designed balanced diet with appropriate micronutrient supplementation may ameliorate the severity of autism symptoms and related abnormal behaviours. PMID- 27275233 TI - The Effect of Combined Therapy ICS/LABA and ICS/LABA plus Montelukast in Patients with Uncontrolled Severe Persistent Asthma Based on the Serum IL-13 and FEV1. AB - BACKGROUND: IL-13 is one of many cytokines responsible for the chronic inflammation of asthma. AIM: The aim of this study was to determine the effect of combined therapy ICS/LABA and ICS/LABA plus Montelukast in patients with uncontrolled severe persistent asthma by analyzing of serum IL-13 and FEV1 before the treatment and after 6 months of therapy. MATERIAL AND METHODS: In study we included two groups. First group with 27 patients were treated with ICS/LABA. Second group with 29 patients were treated with ICS/LABA plus Montelukast. In each of them were measured serum IL-13 levels by the ELISA method and FEV1 before and after 6 months of treatment. Results were statistically analyzed according to the Wilcoxon Pairs Test and T-test. RESULTS: The obtained results in both groups showed that the serum IL-13 before the start of therapy were much higher and after 6 months of treatment significantly reduces their value, which in the second group were more expressed. The difference in the average value of FEV1 in both groups before and after therapy was statistically significant. CONCLUSION: Treatment with ICS/LABA plus Montelukast proved superior compared to therapy of ICS/LABA in patients with uncontrolled severe persistent asthma and allows achievement of well controlled of asthma with subjective clinical improvement. PMID- 27275234 TI - Hook Wire Localization Procedure and Early Detection of Breast Cancer - Our Experience. AB - AIM: The purpose of this study is to describe our experience with needle localization technique in diagnosing small breast cancers. MATERIAL AND METHODS: This retrospective study included a hundred and twenty patients' with impalpable breast lesions and they underwent wire localization. All patients had mammography, ultrasound exam and pathohystological results. We use Mammomat Inspiration Siemens digital unit for diagnosing mammography, machine - Lorad Affinity with fenestrated compressive pad for wire localization and ultrasound machine Acuson X300 with linear array probe 10 MhZ. We use two types of wire: Bard hook wire and Kopans breast lesion localization needle, Cook. Comparative radiologic and pathologic data were collected and analyzed. RESULTS: In 120 asymptomatic women, 68 malignancies and 52 benign findings were detected with mammography and ultrasound. The mean age for patients with malignancy was 58.6 years. According BI-RADS classification for mammography the distribution is our group was: BI-RADS 3 was presented in 6 (8.82%) patients, BI-RADS 4 was presented in 56 (82.35%) patients and BI-RADS 5 was present in 6 (8.82%) of the patients. Most wire localizations were performed under mammographic guidance in 58 from 68 patients with malignant lesions (85.29%) and with ultrasound in 10 (14.7%). According the mammographic findings patients with mass on mammograms were 29 (42.65%), mass with calcifications 9 (13.23%), calcifications 20 (29.41%) and architectural distortions or asymmetry 10 (14.71%). CONCLUSION: Wire localization is a well established technique for the management of impalpable breast lesions. PMID- 27275235 TI - Association between Estrogen Receptor Alpha Gene Polymorphisms and Susceptibility to Idiopathic Scoliosis in Bulgarian Patients: A Case-Control Study. AB - BACKGROUND: The current consensus on idiopathic scoliosis maintains that it has a multifactorial etiology with genetic predisposing factors. AIM: Estrogen receptor alpha gene has been considered as candidate gene of idiopathic scoliosis. MATERIAL AND METHODS: We conducted a case-control study of Bulgarian population samples (eighty patients with idiopathic scoliosis and one hundred-sixty healthy unrelated gender-matched controls) trying to investigate the association between common genetic polymorphisms of estrogen receptor alpha and the susceptibility to idiopathic scoliosis. Molecular detection of the restriction polymorphisms XbaI and PvuII was performed by polymerase chain reaction following by restriction fragment length polymorphism. The statistical analysis was performed by Pearson's chi-squared test. RESULTS: Our case-control study showed statistically significant association between the PvuII polymorphism and susceptibility to idiopathic scoliosis and curve progression. No genotype or allele of XbaI polymorphism was found to be correlated with the onset or severity of the disease. CONCLUSIONS: The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures. PMID- 27275236 TI - Evaluation of C-Reactive Protein in Patients with Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with evidence of systemic oxidative stress, activation of circulating inflammatory cells and increased plasma level of proinflamatory cytokines which include C reactive protein (CRP). CRP is one biomarker of extrapulmonary or systemic consequences of COPD that can be detected. AIM: The aim of this research is to determine whether the level of CRP statistically significantly correlates with the level of bronchial obstruction and the accompanying co-morbidities in patients with COPD. MATERIAL AND METHODS: This study included 80 patients with exacerbation of COPD, hospitalised at the Institute for Lung Diseases and Tuberculosis in Skopje. We measured the level of CRP in the blood in all of these patients in fasting conditions. The classification of COPD patients by the severity of airflow limitation was made according to the actual version of the Global initiative for chronic Obstructive Lung Disease (GOLD). The Student's Independent Samples t-test was used for the statistic analysis of the data. RESULTS: In 52 (65%) of the patients with exacerbation of COPD we detected an increase of the mean value of CRP. The statistical analysis using the Student's t test showed statistically significant differences in the mean value of CRP in patients with different level of bronchial obstruction. Hypertension, heart failure, diabetes mellitus, hyperlipidemia, coronary disease, and CVI were confirmed as co-morbidities in 45 (73.1%) of the patients, hypertension being the most frequent one (40%). The statistical analysis using the Student's t-test showed statistically significant difference of the mean value of CRP (p< 0.01) depending on the number of co-morbidities. CONCLUSION: In 52 (65%) of the patients with exacerbation of COPD, were detected an increase of the mean value of CRP. The mean values of CRP statistically significantly correlate with the level of bronchial obstruction and the number of co-morbidities in patients with COPD. PMID- 27275237 TI - Liver Enzymes in Children with beta-Thalassemia Major: Correlation with Iron Overload and Viral Hepatitis. AB - BACKGROUND: Beta Thalassemia is the most common chronic hemolytic anemia in Egypt (85.1%) with an estimated carrier rate of 9-10.2%. Injury to the liver, whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST). AIM: Evaluating the potentiating effect of iron overload & viral hepatitis infection on the liver enzymes. PATIENTS AND METHODS: Eighty (80) thalassemia major patients were studied with respect to liver enzymes, ferritin, transferrin saturation, HBsAg, anti-HCV antibody and HCV-PCR for anti-HCV positive patients. RESULTS: Fifty % of the patients were anti-HCV positive and 55% of them were HCV-PCR positive. Patients with elevated ALT and AST levels had significantly higher mean serum ferritin than those with normal levels. Anti-HCV positive patients had higher mean serum ferritin, serum ALT, AST and GGT levels and higher age and duration of blood transfusion than the negative group. HCV-PCR positive patients had higher mean serum ferritin and serum ALT and also higher age and duration of blood transfusion than the negative group. CONCLUSION: Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload. PMID- 27275238 TI - Correlation between the Amount of Anti-D Antibodies and IgG Subclasses with Severity of Haemolytic Disease of Foetus and Newborn. AB - AIM: The aim of this study was to investigate the influence of subclasses to IgG anti-D on the intensity of hemolytic disease of fetus and newborn (HDFN) at 45 fetuses/newborns with symptoms of mild and severe HDFN in Republic of Macedonia. MATERIAL AND METHODS: In retrospective and prospective studies, in a period of 10 years, from 2004 to 2014, there have been immunohemathology tests performed on 22 009 samples on serums of pregnant women. RESULTS: At 37.78% of the total number of tested patients, IgG1 and IgG3 was the reason for severe HDFN. At 17.77% of the total number of tested patients, which had only IgG1detected, was the reason for serious intensity of HDFN. The correlation of the titer to anti-D antibodies in the mother's serum and the intensity of HDFN were researched in 48 newborns. The titers between 1:8 and 1:32 resulted in 3 cases of HDFN with symptoms of severe disease and in 4 cases there were no signs of HDFN. At 12 women that had a titre between 1:32 and 1:512, five of the newborns developed severe HDFN, and seven had symptoms of mild and weak intensity form. In 3 cases the titer was higher than 512, and out of them one newborn had weak symptoms of HDFN, one developed severe HDFN and one ended with foetal death. Only in one case the titer reached a value higher than 1000, and it ended with a fetal death. CONCLUSIONS: The titers of the pregnant women serum those are lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The research study results suggest that IgG1 and IgG3 should be included in a multi - parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer hight and the significance of the antibodies. PMID- 27275239 TI - Combined Adiponectin Deficiency and Resistance in Obese Patients: Can It Solve Part of the Puzzle in Nonalcoholic Steatohepatitis. AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths. AIM: To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD. METHODS: Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level. RESULTS: According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 +/- 2.569 ng/dl in NASH vs. 5.138 +/- 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 +/- 0.4671 vs. 1.0688 +/- 0.3965 in non-NASH). CONCLUSION: Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients. PMID- 27275240 TI - Comparison of Serum IgG Antibody Test with Gastric Biopsy for the Detection of Helicobacter Pylori Infection among Egyptian Children. AB - BACKGROUND: In developing countries, Helicobacter pylori (H. pylori) infection is mainly acquired during childhood and may be a predisposing factor for peptic ulcer or gastric cancer later in life. Noninvasive diagnostic tools are particularly useful in children for screening tests and epidemiological studies. Data on serologic testing of children are lacking. Accurate noninvasive tests for diagnosing Helicobacter pylori infection in children are strongly required. AIM: The aim of this study was to evaluate the performance of a serological test (serum IgG antibody for H. pylori) in Egyptian children with recurrent abdominal pain necessitating endoscopy. SUBJECTS AND METHODS: One hundred children, referred to the endoscopy unit at Mansoura University. Upper endoscopy was done for each with rapid urease test (RUT) and histological examination as the gold standard test for detection of H. pylori infection. Serum samples were collected for detecting IgG for H. pylori infection. RESULTS: The mean age of the subjects included in the study was 7.23 +/- 1.94 year. Serological test (IgG to H. pylori) was positive in 60% of all cases. A highly significant association between the standard test and the serological test at a cutoff > 10 U/ml at p = 0.001 were detected for the diagnosis of H. pylori infection. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the IgG antibody a cutoff > 10 U/ml, were 96.5%, 93%, 13.83, 0.038 respectively. CONCLUSION: Serum IgG antibody to H. pylori infection has a high diagnostic value and can be considered as a suitable and reliable noninvasive test for detection of H. pylori infection. PMID- 27275241 TI - Fine Needle Aspiration in Thyroid Nodules - One Year Experience. AB - AIM: To estimate suspect nodule for benign or malignant characteristics, and to verify cytological features of the node with the fine needle aspiration (FNA) under ultrasound. DESIGN: A total of 106 patients were analyzed. FNA biopsy was performed at outpatient clinic via ultrasound. Inform consent was signed for each patient. Preparation of procedure with local anaesthesia was made by assistant nurse. PROCEDURE: Parallel approach of ultrasound guided fine needle aspiration (USGFNA) was used for each patient. This approach allows the operator to observe needle penetration, location and pathway of the entire needle within the neck, thyroid and nodule, which remain visible on the monitor. As a side effect commonly noticed mild pain and dizziness were recorded. RESULTS: General findings: According the gender, 96 (90.5%) of them were women and 10 (9.5%) men. Median age was 47 +/- 9 years. Cytological findings: 5 patients were with papillary carcinoma, 3 with Hurtle cell metaplasia, 1 follicular tumour and 1 with unclear differentiation. CONCLUSION: Close collaboration between endocrinologists, morphologists and surgeons in a multidisciplinary frame is the key to correct preoperative thyroid cancer diagnosis and optimal treatment. FNA biopsy remains the most accurate diagnostic method in detecting thyroid cancer. PMID- 27275242 TI - Bristow-Latarjet Technique: Still a Very Successful Surgery for Anterior Glenohumeral Instability - A Forty Year One Clinic Experience. AB - AIM: To evaluate the functional outcomes of the Bristow-Latarjet procedure in patients with recurrent anterior glenohumeral instability. PATIENTS AND METHODS: Personal clinical records of 42 patients with 45 operated shoulders were reviewed retrospectively. Patient age at time of first dislocation, injury mechanism, and number of recurring dislocations before surgery were recorded. The overall function and stability of the shoulder was evaluated. RESULTS: Thirty five (78%) of the scapulohumeral humeral instabilities were caused by trauma. The mean number of recurring dislocations was 9 (95% confidence interval [CI], 0-18); one patient had had 17 recurrences. Mean follow-up 46 months (95% CI, 16-88). No dislocation happened postoperatively. Four patients have fibrous union (9%). Only two had clinical sign of pain and discomfort. One of them was reoperated for screw removal with very good post-operative result. The overall functional outcome was good, with a mean Rowe score of 88 points (95% CI, 78-100). Scores of 27 (64%) of the patients were excellent, 9 (22%) were good, 4 (9.5%) were fair, and 2 (4.5%) were poor. CONCLUSION: The Bristow-Latarjet procedure is a very good surgical treatment for recurrent anterior-inferior instability of the glenohumeral joint. It must not be used for multidirectional instability or psychogenic habitual dislocations. PMID- 27275244 TI - Klippel Trenaunay Syndrome: A Case Report in an Adolescent Nigerian Boy. AB - AIM: This is to report a case of Klippel Trenauay Weber syndrome in a fifteen year old Nigerian boy. This is a rare syndrome and it is the first case to be reported in UCTH Calabar. CASE PRESENTATION: Product of a full term uneventful pregnancy, delivered to non-consanguineous apparently healthy parents. At birth was noted to gradually develop swelling on the right leg, worse at the right foot. There was crossed hemi-hypertrophy with right leg bigger than the left. As child grew symptoms worsened, parents separated and eventually he was abandoned to the streets. He presented at University of Calabar Teaching Hospital for medical care at the age of fifteen years with lymphatic obstruction, persistent foul smelling drainage, lipodermatosclerosis of right foot as well psycho-social and financial constraints. The diagnosis was made with x-rays and Doppler studies of the lower limb vessels. He is currently being managed conservatively with compression dressings on the affected limbs, Antibiotics for the infection and analgesics. De-bulking surgery is being anticipated at this time. CONCLUSION: This is a case of KTWS presenting in adolescence and due to its rarity in Nigeria, this report is to increase awareness. PMID- 27275243 TI - Sleep Deficiency is a Modifiable Risk Factor for Obesity and Cognitive Impairment and Associated with Elevated Visfatin. AB - AIM: To study the interaction between sleep deprivation, obesity and cognitive functions, and the effect of following a balanced low caloric diet and increasing sleep duration on those variables. SUBJECTS AND METHODS: Ninety two obese females with mean age 47.00 +/- 2.00 years and body mass index (BMI) 36.14 +/- 3.00 kg/m2 were divided into 3 groups according to their sleeping hours. They followed balanced low-caloric diet and were instructed to increase sleeping hours. Full clinical examination, 24 hours dietary intake recall, anthropometric measurements, mini mental state test, questionnaire for subjective sleep and life style evaluation were performed at baseline and after 2 months. Serum visfatin, fasting blood glucose and C-peptide were assessed; Modified homeostatic model assessment of insulin resistance was calculated. RESULTS: About one third of our sample slept less than 6 hours daily, group (1), all patients had elevated visfatin serum level (33.87 +/- 2.8 ng/ml) with the highest level in group (1). At base line, group (1) showed the highest BMI, lowest cognitive functions, highest visfatin level and highest insulin resistance (P < 0.05). After 2 months of intervention, improvement was recorded in all variables, with the best improvement in group (1) after extending sleep duration (P < 0.05). CONCLUSION: Sleep deprivation may be a modifiable risk factor for obesity, cognitive impairment and visfatin elevation. PMID- 27275245 TI - Sjogren's Syndrome and Silicosis - a Case Report. AB - Sjogren's syndrome is an autoimmune disease of unknown etiology where immune response to self-antigens is believed to result from interactions between genetic and environmental factors. We describe the case of a patient who has been diagnosed with Sjogren's syndrome based on typical clinical and immunological parameters. The clinical picture was dominated by the respiratory symptoms, and radiographic and multislice computed tomography examination of the chest showed certain changes characteristic of pneumoconiosis. Given that the patient has worked in a foundry where he has been exposed to the silica dust, he was subject to examination by occupational health specialists under the suspicion of lung silicosis, who confirmed the silicosis. This case report points to the possible connection between a professional exposure to silica and Sjogren's syndrome. Occupational exposure to silica is a possible risk factor for the development of autoimmune diseases, and in the evaluation of patients with connective tissue diseases it is important to consider work-related history. PMID- 27275246 TI - Beetroot-Carrot Juice Intake either Alone or in Combination with Antileukemic Drug 'Chlorambucil' As A Potential Treatment for Chronic Lymphocytic Leukemia. AB - Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms). It is characterized by a progressive accumulation of functionally incompetent lymphocytes. Patients with leukemia often seek unconventional treatments not prescribed by hematologist in order to improve their cancer treatment outcome or to manage symptoms. In the present report, a 76 year-old patient was diagnosed with B-cell chronic lymphocytic leukemia (B-CLL). Beetroot-carrot juice is used as a complementary and or/alternative therapy used in conjunction with conventional leukemic treatment (chlorambucil) that has been a standard first-line chemotherapeutic agent for patients with CLL and known to have serious and undesirable side-effects. After one month and 15 days of administration of beetroot-carrot juice therapy, the patient had improved appetite, a sense of general well-being and increased vigor daily activities. Furthermore, beetroot-carrot juice was used as an adjuvant to chlorambucil resulted in a substantial reduction in leukocytes and lymphocytes count in peripheral blood and improvement in the relevant biochemical parameters. Beetroot carrot juice can be used as an effective treatment for CLL alone or in combination with chlorambucil when taken orally with regular diet on daily basis. PMID- 27275247 TI - Comparison of Results from Inpatient and Outpatient Treatment of Tuberculosis in Republic of Macedonia. AB - BACKGROUND: The successful treatment of patients with active tuberculosis is one of the priorities in the Tuberculosis Control Programs. AIM: The aim was to establish whether there was a statistically significant difference in the treatment outcome in patients with tuberculosis who began their initial treatment phase and/or pursued it as inpatient, as opposed to patients with tuberculosis who underwent their entire treatment regime as outpatient. Moreover, our goal was to determine whether there is a statistically significant difference in the outcome from the treatment between patients with tuberculosis who were hospitalized up to one month, two months, or more than two months. MATERIALS AND METHOD: The study includes 355 patients, divided into two groups. The first group, which consists of 219 patients, began their initial treatment phase as inpatient, and then they continued the treatment as outpatient. The second group, 136 patients, underwent their entire treatment as outpatient. The treatment outcome is determined with every patient (cured, treatment completed, treatment default, treatment failed, died, treatment in progress). For the statistical data analysis and for establishing the significance of the findings regarding the differences between the two groups we used the Pearson Chi-Square Test and the Yates Corrected Test. RESULTS: The statistical analysis with the Pearson Chi Square Test showed that the treatment outcome does not significantly depend on the model of treatment (p = 0.31). The statistical data analysis showed that there is no statistically significant difference in the achievement of conversion of the bacterial result of the sputum at the end of the initial phase of treatment regarding the studied groups (p = 0.89). The statistical data analysis showed that the length of inpatient treatment affects the outcome of the treatment and that the difference is statistically highly significant (p < 0.00005). CONCLUSION: There are no statistically significant differences in the sputum conversion and the treatment outcome among inpatient/outpatient with tuberculosis or outpatient only; however, the length of inpatient treatment is statistically significant regarding its effect on the treatment outcome. PMID- 27275248 TI - Cost-Effectiveness of Thrombolytic Therapy, Compared with Anticoagulants Therapy in the Treatment of Acute Myocardial Infarction in Albania. AB - AIM: The study aim is to evaluate the cost-effectiveness of thrombolytic treatment in acute MI comparing with anticoagulants therapy and between each other thrombolytic (SK, r-Pa). MATERIAL AND METHODS: We used a prospective registry of all patients admitted for acute myocardial infarction in intensive care units in Tirana. The average drugs cost was calculated for the hospitalization period in Albanian money (ALL). Survival and life quality were estimated by phone contact 1 year after acute MI. RESULTS: Anticoagulant group cost is 23865.3 ALL (170.5?), SK group cost is 54148.63 ALL (386.7?), r-Pa group has a cost of 92184.90 ALL (658.5?). In the group treated with SK the hospital survival is 100%, while in the control group 88.8%. Reteplase group has a lower period of stay in hospital than SK group 13.04 days vs. 17.97 days, mean age in group treated with r-Pa is 64.29 +/- 10.03 approximate with anticoagulant group mean age 64.17 +/- 11.08; differ significantly with SK group mean age 56.75 +/- 10.04. Survival after 1 year was 96.4% for r-Pa and 96.9% SK. CONCLUSIONS: SK and r-Pa are successful thrombolytics with high effectiveness. It is gained a higher survival with the thrombolytic treatments. Reteplase is well tolerated in older patients than SK, is easier to apply than Streptokinase, but has higher cost. PMID- 27275249 TI - The Heavy Metals in Agrosystems and Impact on Health and Quality of Life. AB - The metal is a chemical element that conducts electricity well and heat, and the nonferrous metals builds cations and ionic bonds. Heavy metals include metals whose density is higher than 5 g/cm(3). The whole range of the metal is in the form of essential trace elements, essential for a number of functions in the human body, and its deficiency results in a lack of occurrence of a serious symptom. The best examples are anemia lack of iron, lack of chromium in diabetes, growth problems in lack of nickel. Other elements such as lead, cadmium, mercury, arsenic and molybdenum have been shown to exhibit large quantities of toxic effects. The paper examines the problem of heavy metals originating from agriculture on agroecosystems. This group of pollutants is considered the most important cause of degradation of soil quality, surface and groundwater and direct causal adverse effects on human and animal health. In order to complete the environmental monitoring of pollutants, these main categories, origins, and possible negative impacts of the basic principles of preventing their toxic effects were examined. PMID- 27275250 TI - An Assessment of Mental Health Status of Undergraduate Medical Trainees in the University of Calabar, Nigeria: A Cross-Sectional Study. AB - BACKGROUND: The mental health status of medical students has been proven to be poor compared to their peers in other disciplines and has led to grave personal and professional consequences. This subject has however remained largely unexplored in our medical school. AIM: The study was therefore conducted to assess the prevalence of mental health of medical students in the University of Calabar, Cross river state, Nigeria. METHODOLOGY: A descriptive cross-sectional survey of 451 randomly selected medical students from the pre-clinical and clinical levels of study in the University of Calabar. A self administered questionnaire including the GHQ12 was used to elicit information from the respondents. A score of >= 3 suggested poor mental while a score < 3 represented good mental health. Data were summarized using proportions, and chi2 test was used to explore associations between categorical variables. Level of significance was set at p < 0.05. RESULTS: The mean age of the respondents was 23.4 +/- 4.3 years, 63.8% were males, 34.8% were from the preclinical and 65.2% from clinical levels of study. Based on the GHQ categorisation, 39.2% had a poor mental health status, compared to 60.8% with good mental health status. The factors significantly associated with poor mental health, were recent experience of mistreatment by trainers or colleagues, perceived inadequate monthly allowance and perception that medical training is stressful (p < 0.05). CONCLUSION: With more than a third of undergraduate medical trainees with traits of poor mental health, provision of accessible mental health services/counselling is strongly recommended early in their training. PMID- 27275251 TI - Challenging Role of Dietary Aflatoxin B1 Exposure and Hepatitis B Infection on Risk of Hepatocellular Carcinoma. AB - Aflatoxins (AFT) are poisonous substances which are classified in Group 1 carcinogenic agents to humans by International Agency for Research on Cancer (IARC). AFT can occur naturally in food commodities (maize, corn, rice) as a result of fungal contamination in hot and humid environments. In the food, toxin contamination can remain during manufacturing and long after fungi have stopped being biologically active. Aflatoxin B1 (AFB1) is the most dominant and potent agent from all AFT. In developing countries, high exposure to AFB1 can cause chronic toxicity and usually increases the incidence of Hepatocellular Carcinoma (HCC). However, in these regions hepatitis B is the most common risk factor for HCC cases. Many researches were aimed to enlighten the mechanism and the role of two etiological agents on risk of HCC, but the obtained data was conflicting with each other. It was uncertain that the indicators/biomarkers might be the contribution of the carcinogenic status of the patient; and, the biomarker samples from the subject may only reflect the recent effects of the toxin exposure after consumption of AFB1 contaminated commodities. The studies were facing with the errors of methods which were un-fit to enlighten the possible interaction between Hepatitis B and AFB1 on contribution to HCC. It was pivotal to understand the effect of each risk factor in order to prevent and improve public health in poor and undeveloped regions. Although some of the studies evaluate AFB1 alone as a considerable factor on HCC risk, according to this review it was concluded vice versa. This study was aimed to clarify the main etiological agent of HCC where AFB1 and HBV are endangering public health. In additionally, the purpose was to enlighten the possible synergistic effect between these two factors among HCC pathogenesis. Hence forth, appropriate and right applications could be conducted in undeveloped countries in order to protect public health. PMID- 27275252 TI - Association between VNTR Polymorphism in Promoter Region of Prodynorphin (PDYN) Gene and Methamphetamine Dependence. AB - AIM: Prodynorphin (PDYN; OMIM: 131340) is the precursor of the dynorphin related peptides which plays an important role in drug abuse. Previous studies have been shown that the expression of PDYN is regulated by a genetic polymorphism of VNTR in the promoter region of the gene. MATERIALS AND METHODS: The present case control study was performed on 52 (41 males, 11 females) methamphetamine dependence patients and 635 (525 males, 110 females) healthy blood donors frequency matched with the patients according to age and gender, as a control group was participated in the study. RESULTS: The genotypes of VNTR PDYN polymorphism were determined using PCR method. The HL (OR = 1.22, 95%CI: 0.67 2.20, P = 0.500) and LL (OR = 0.86, 95%CI: 0.28-2.57, P = 0.792) genotypes does not alter the risk of methamphetamine dependence, in comparison with the HH genotypes. CONCLUSION: The present study revealed no association between the VNTR polymorphism in the promoter region of the PDYN gene and methamphetamine dependence risk. PMID- 27275253 TI - Chemical Composition and Antifungal Activity of Ocimum basilicum L. Essential Oil. AB - BACKGROUND: The leaves of Ocimum basilicum L. (basil) are used in traditional cuisine as spices; its essential oil has found a wide application in perfumery, dental products as well as antifungal agents. AIM: To assess the chemical composition as well as the in vitro antifungal activity of O. basilicum L. essential oil against Aspergillus flavus fungal growth and aflatoxin B1 production. MATERIAL AND METHODS: The essential oil of O. basilicum was obtained by hydrodistillation and analysed using gas chromatography (GC) and GC coupled with mass spectrometry (GC/MS). The essential oil was tested for its effects on Aspergillus flavus (A. flavus) mycelial growth and aflatoxin B1 production in Yeast Extract Sucrose (YES) growth media. Aflatoxin B1 production was determined by high performance liquid chromatography (HPLC). RESULTS: Nineteen compounds, representing 96.7% of the total oil were identified. The main components were as follows: linalool (48.4%), 1,8-cineol (12.2%), eugenol (6.6%), methyl cinnamate (6.2%), alpha-cubebene (5.7%), caryophyllene (2.5%), beta-ocimene (2.1%) and alpha-farnesene (2.0%). The tested oil showed significant antifungal activity that was dependent on the used oil concentration. The complete inhibition of A. flavus growth was observed at 1000 ppm oil concentration, while marked inhibition of aflatoxin B1 production was observed at all oil concentrations tested (500, 750 and 1000 ppm). CONCLUSION: These results confirm the antifungal activities of O. basilicum L. oil and its potential use to cure mycotic infections and act as pharmaceutical preservative against A. flavus growth and aflatoxin B1 production. PMID- 27275254 TI - Effect of Streptozotocin on Plasma Insulin Levels of Rats and Mice: A Meta analysis Study. AB - BACKGROUND: In the studies focusing on diabetic organisms, Streprozotocine (STZ) is a frequently used agent to induce diabetes in rats and mice. However the current studies do not represent practical importance of their statistical findings. For showing practical importance of the differences in plasma insulin levels of diabetic rats and mice induced by STZ, there should be a statistical synthesis regarding statistical findings of the studies. AIM: The purpose of this study is to make a meta-analysis of the studies on the effect of STZ on plasma insulin levels in diabetic rats and mice. MATERIALS AND METHODS: In this study 39 effect sizes (37 studies) about levels of plasma insulin were analyzed by calculating individual effect sizes (d) and mean effect size. RESULTS: The effect sizes were between -13.7 and +65.3 and the mean effect size value (+9.33) represented a large effect indicating that STZ was an effective agent to significantly decrease plasma insulin levels of diabetic rats and mice. CONCLUSION: It can be said that the differences in plasma insulin levels between STZ-applied and no application groups has a practical importance in making animal model of diabetes. PMID- 27275255 TI - Change in Profile of Entrants in a Brazilian Large Cardiovascular Rehabilitation Service. AB - BACKGROUND: There are references regarding physical activity and cardiovascular disease since the nineteenth century. New evidences support that cardiac rehabilitation is closely related to therapeutic success after major coronary events. Although the benefits of cardiac rehabilitation programs are well established, referencing and enrolment in such services remain low. AIM: The aim of this paper is to describe the profile changes throughout the years in a large cardiac rehabilitation service in Brazil. MATERIAL AND METHODS: This is a retrospective analysis of medical records of all patients referred to cardiac rehabilitation service of the Institute of Sports Medicine, University of Caxias do Sul from March 2003 to July 2014. Data collection was carried out using SPSS software and the statistical analysis with Student's t-test, ANOVA test and chi square test. RESULTS: It has seen a substantial increase of patients, mostly routed via universal health system, also an increase of post-myocardial infarction patients and ex-smokers. Also, it was seen few patients in the 7th and 8th life decades, and men were in majority since the beginning. CONCLUSION: An increase in the number of patients referred by universal health system occurred because there is a governmental interest in this type of program. About tobacco, hospitalizations appear to be influential in the decision of abandonment. There was a substantial increase of patients with more severe disease which is in accordance with the latest guidelines of Cardiovascular and Metabolic Rehabilitation. PMID- 27275256 TI - Fetuin-A and Ghrelin Levels in Children with End Stage Renal Disease and the Effect of a Single Hemodialysis Session on Them. AB - BACKGROUND: Fetuin-A and ghrelin have been implicated in cardiovascular diseases and mortality among end stage renal disease patients. The exact mechanisms have not been fully elucidated. There is robust data supporting an association between ghrelin and various cardiovascular conditions, and some common processes such as inflammation, oxidative stress, and endoplasmic reticulum stress have been implicated. AIM: This study was conducted to assay serum fetuin-A and ghrelin in chronic renal failure pediatric patients and to study changes in their level that may occur after a single hemodialysis. MATERIAL AND METHODS: Forty nine pediatric patients suffering from ESRD on maintenance hemodialysis (HD), 20 patients with chronic renal failure (CRF) not on dialysis and 35 healthy subjects as control group were included. The mean age of the study population was 10.58 +/- 3.94, 10.62 +/- 3.24 and 10.61 +/- 3.97 years respectively. Serum fetuin-A and plasma acyl ghrelin levels were measured by using ELISA method. RESULTS: The present study revealed that predialysis serum fetuin-A level was significantly increased in pediatric HD patients compared with the normal population, while ghrelin levels were significantly reduced. Furthermore, serum levels of fetuin-A decreased significantly after a single HD session. CONCLUSION: Our study concluded that fetuin-A and acyl ghrelin may play a role in inflammatory process among HD pediatric patients which may account for cardiovascular insults and mortality but their use as biochemical markers among ESRD pediatric patients have limitations due to wide fluctuations. PMID- 27275257 TI - Orthostatic Reactivity in Patients with Ischemic Stroke in the Chronic Period. AB - AIM: This study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on orthostatic reactivity in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: An active orthostatic test is used for the evaluation of the orthostatic reactions. The arterial blood pressure and heart rate were defined in the 10 minutes of supine position, before and after 1, 5 and 10 minutes of active upright position. The orthostatic autoregulation is evaluated four times - at the beginning of the study, on the 10th day, on the 1st month and three months after the start of the KT. The classification by Thulesius was used to separate the patients into two groups depending on the type of their orthostatic reactivity. RESULTS: At the beginning of the study of infringements symptomatic type orthostatic reactivity (SOR) was observed in 24 patients and hypertensive type orthostatic reactivity (HOR) was observed in the remaining 32 patients. Once applied SKTM establish improvement of orthostatic autoregulation for the groups SOR and HOR at the 10th day and the 1st month with a level of significance p <0.05. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as an adapted exercise program at home, has significantly improved the orthostatic reactivity in patients with orthostatic dysregulation due to the ISChP. PMID- 27275258 TI - Bifidobacterium lactis in Treatment of Children with Acute Diarrhea. A Randomized Double Blind Controlled Trial. AB - BACKGROUND: Probiotics are becoming increasingly popular treatment for children diarrhea. Although there are several probiotic strains potentially useful, researches were often limited to certain strains. AIM: To test Bifidobacterium lactis on morbidity of acute diarrhea in children less than 2 years. SUBJECTS AND METHODS: A randomized double-blind controlled clinical trial was conducted in 50 children (1 - 23 months) admitted with acute diarrhea to the Pediatric Hospital, Cairo University and were randomly assigned to receive in addition to usual treatment of diarrhea according to WHO guidelines; one of two treatments either milk formula non-supplemented (n = 25) or supplemented (n = 25) with Bifidobacterium lactis 14.5 * 10(6) CFU/100 ml daily for one week. Primary outcomes were frequency and duration of diarrhea and hospital stay. Secondary outcomes were duration of fever and vomiting episodes. Safety and tolerance were also recorded. RESULTS: On admission, patients' characteristics of both groups (50 cases) were similar. For children who received the probiotics for one week; mean duration of diarrhoea was shorter than in controls (3.12 +/- 0.92 vs. 4.10 +/- 0.94 days) (P = 0.02), number of motions per day was less than in controls (3.96 +/- 0.62 vs. 4.46 +/- 0.85) (P = 0.04) and discharge from hospital <2 days was more frequent than in controls (72% vs. 44%) (P = 0.048). There was no effect on fever (P = 0.63) or vomiting (P = 0.54). CONCLUSION: Bifidobacterium lactis probiotics in supplemented milk formula decreased significantly frequency, duration of diarrhea, and hospital stay than usual treatment alone in children with acute diarrhea. Additional researches on other uncommon local probiotic species should be encouraged. PMID- 27275259 TI - Interventional Treatment of Pulmonary Valve Stenosis: A Single Center Experience. AB - BACKGROUND: Percutaneous pulmonary valvuloplasty is well established treatment of choice in pulmonary valve stenosis. AIM: The aim of our study was to present our experience with the interventional technique, its immediate and mid-term effectiveness as well as its complication rate. MATERIAL AND METHODS: The study included 43 patients, where 33 (74%) of them were children between the age of 1 month and 15 years. RESULTS: The procedure was successful in 38 patients or 90%. Mean peak to peak transvalvular gradient was reduced from 91.2 mmHg (55-150 mmHg) to 39.1 mmHg (20-80 mmHg). Follow- up of patients was between 2 and 13 years and included echocardiographic evaluation of pulmonary valve gradient, right heart dimensions and function as well as assessment of pulmonary regurgitation. We experienced one major complication pericardial effusion in a 5 months old child that required pericardiocenthesis. Six patients (13.9%) required a second intervention. During the follow up period there was significant improvement of right heart function and echocardiography parameters. Mild pulmonary regurgitation was noted in 24 (55%) patients, and four (9%) patients developed moderate regurgitation, without affecting the function of the right ventricle. CONCLUSIONS: Percutaneous pulmonary valvuloplasty is an effective procedure in treatment of pulmonary stenosis with good short and mid-term results. PMID- 27275260 TI - Bone Density, Osteocalcin and Deoxypyridinoline for Early Detection of Osteoporosis in Obese Children. AB - AIM: This study aimed at comparing between bone density using DEXA, serum osteocalcin and urinary DPD in obese and non obese prepubertal children. METHODS: After taking the consent of eighty children they were subjected to: full examination, anthropometric measurements, blood samples were withdrawn to determine serum osteocalcin, Ca, Ph, alkaline phosphatase, and urinary DPD. Bone densities, body composition of the whole body were examined using DEXA. Data were analyzed using SPSS. RESULTS: All anthropometric variables showed significant increase in obese children except for height in comparison to control group. Total mass, lean + BMC, lean, fat, area, BMC, BMD and Z score of the whole body were significantly increased in obese children. Serum calcium showed significant increase while alkaline phosphatase was significantly decreased in obese children. DPD showed no significant difference between obese and non obese children. Significant negative correlation was found between ca, lean, lean + BMC and total mass. Serum alkaline phosphatase showed also a significant negative correlation with (lean + BMC and total mass). Serum osteocalcin showed negative significant correlation with area, BMC, BMD, lean and Z score. CONCLUSION: Obese children showed significant increase in anthropometric and DEXA parameters, increase in serum calcium and significant decrease in serum alkaline phosphatase. Osteocalcin was negatively correlated with most of DEXA results. PMID- 27275261 TI - A Case of Unicornuate Uterus with Atypical Located Hyperstimulated Ovary after in Vitro Fertilization Pre-Embryo Transfer (IVF-ET). AB - The authors describe a case of a congenital Mullerian anomaly, uterus unicornis with missing right fallopian tube. An in Vitro Fertilization Pre-Embryo Transfer (IVF-ET) procedure was done and presently is known that the patient has left fallopian tube and left ovary, two kidneys, and right ovary is missing. No diagnostic laparoscopy and hysteroscopy were done, only hysterosalpingography (HSG) before the IVF procedure. Several days after the follicular puncture of the left ovary the patient was urgently admitted to the hospital for specialized gynaecology in Varna. Transabdominal ultrasonography showed right ovary atypically located immediately next to the liver and with emerging theca-lutein cysts. PMID- 27275262 TI - The Surgical Lips Deformity Corrected with Hyaluronic Fillers: A Case Report. AB - BACKGROUND: Hyaluronic filler is a sterile, biodegradable, viscoelastic, isotonic, transparent injectable gel implant which was approved by Food and Drug Administration (FDA) 1996. It is used for face reconstruction and modelling. CASE PRESENTATION: We report the case of a 40-year-old Serbian woman who presented after surgery of cleft lip, primary and secondary palate. We performed a biphasic therapy; in the first stage in the zone semimucosis lips is initially carried incision scar tissue. The second stage is placed hyaluronan implant. CONCLUSION: This case illustrates that, although hyaluronic fillers used mainly for correction of healthy tissue can be successfully used in the treatment of postoperative scars. PMID- 27275263 TI - A Case of Secondary Abdominal Pregnancy after in Vitro Fertilization Pre-Embryo Transfer (IVF-ET). AB - The authors describe a rare case of secondary abdominal pregnancy after in vitro fertilization pre-embryo transfer (IVF-ET). Ultrasonography was applied to image ectopic gestational sac containing a yolk vesicle and located adjacent to the anterior uterine wall and left adnexa. Laparoscopy was done on the same day followed by sinistral salpingectomy due to tubal abortion indications. Intraabdominal examination showed chorionic structures penetrating pl. vesicouterina. Histological tests confirmed the EP diagnosis in the second material, i.e. indications of secondary abdominal pregnancy. PMID- 27275264 TI - Cystic Adventitial Disease in Former Athlete. AB - In this paper we present a 39-year old former athlete complaining with pain in his legs during long walk resembling to intermittent claudication. Color duplex scan described a popliteal artery with 10 mm in diameter with mural thrombus that caused stenosis 75% of lumen. Digital subtraction angiography demonstrated a stenosis of right popliteal artery. The suspicion for Cystic adventitial disease was set. The patient was operated on by posterior direct approach. After incision, a yellowish viscous material was observed in adventitia. Partial resection of the affected popliteal artery and replacement by an autogenous great saphenous vein graft was performed. Patient was dismissed on the seventh postoperative day, in good condition and without any complication. Cystic adventitial disease of the popliteal artery should be considered in the differential diagnosis of intermittent claudication, especially in former sportsmen patients. Partial resection of the affected popliteal artery and replacement by an autogenous great saphenous vain graft produces excellent results. PMID- 27275265 TI - Perioperative Challenges in Repeat Bladder Exstrophy Repair - Case Report. AB - Bladder exstrophy is a rare congenital malformation. It presents as leakage of urine in the anterior abdominal wall following defects in midline anterior abdominal wall skin and bladder. We report the use of combined general anaesthesia and caudal epidural analgesia in a 4yr old boy for repeat bladder exstrophy repair. Problems of prolonged surgery and the challenges of pain and sedation management in the post operative period are discussed. PMID- 27275266 TI - A Very Rare Presentation of Multiple Myeloma: Unilateral Raccoon Eye. AB - Multiple myeloma (MM), the second most common hematological malignancy, is caused by the accumulation of monoclonal plasma cells in bone marrow. It accounts for 10 15% of deaths from hematological malignancies and approximately 2% of deaths from cancer. The median age at presentation is 70 years old. The diagnosis is incidental in 30% of cases. MM is often discovered through routine blood screening with a large gap between the total protein and the albumin levels. Two thirds of patients complain of bone pain, especially lower back pain. MM could be diagnosed after a pathologic fracture occurs in one third of patients. Presentation with symptoms related to hyperviscosity, hypercalcemia and bleeding tendency could also be observed. A rare presentation of MM is peri-orbital ecchymotic lesion (raccoon eye). Here, we report a 64 years old, male patient presented with unilateral raccoon eye and high erythrocyte sedimentation rate (ESR) to internal medicine outpatient. The patient was referred to hematology outpatient and was diagnosed with multiple myeloma. PMID- 27275267 TI - Systemic Lupus Erythematosus and Secondary Antiphospholipid Syndrome after Thymectomy for Myasthenia Gravis - A Case Report. AB - INTRODUCTION: Systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are autoimmune diseases that show some similarities: a higher incidence in young women, relapsing-remitting course and positive anti-nuclear antibodies (ANA). However, they are two different clinical syndromes, which can coexist or precede each other. Thymectomy is a therapeutic option for patients with severe MG or thymoma. There are many cases of SLE after thymectomy described in the literature, so the question arises whether thymectomy predisposes patients to SLE and what are imunopathogenetic mechanisms behind this process. CASE REPORT: We report a case of a patient who was diagnosed with SLE and secondary antiphospholipid syndrome (APS) 28 years after thymectomy for MG. Clinical picture of SLE was characterized by cutaneous and articular manifestations, polyserositis, lupus nephritis and immunological parameters showed positive ANA, anti-ds-DNA, excessive consumption of complement components, positive cryoglobulins. Clinical and laboratory immunological parameters for the diagnosis of secondary APS where also present. The patient was initially treated with glucocorticoids followed by mycophenolate mofetil. During one year follow-up patient was in a stable remission of SLE. CONCLUSION: Thymectomy for MG may predispose SLE development in some patients. Further studies are needed to better understand the connection between these two autoimmune diseases. PMID- 27275268 TI - Fulminate Hepatic Failure in a 5 Year Old Female after Inappropriate Acetaminophen Treatment. AB - BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses. CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day. The blood level of acetaminophen after 10 hours of the last administered dose was 32 mg/l. The patient presented with high fever, jaundice, lethargic, agitating with abdominal pain accompanied by encephalopathy. The liver function test revealed with high level of alanine aminotransferase 5794 UI/l and aspartate aminotransferase 6000 UI/l. Early initiation of oral N-acetylcysteine (NAC) after biochemical evidence of liver toxicity was beneficial with rapid improvement of liver enzymes, hepatic function and encephalopathy. During the course of the illness the child developed acute pancreatitis with hyperamylasemia 255 UI/L and hyperlypasemia 514 UI/L. Patient totally recovered within 29 days. CONCLUSION: Healthcare providers should considered probable acetaminophen toxicity in any child who has received the drug and presented with liver failure. When there is a high index of suspicion of acetaminophen toxicity NAC should be initiated and continued until there are no signs of hepatic dysfunction. PMID- 27275269 TI - Treatment of Gingival Hyperpigmentation by Diode Laser for Esthetical Purposes. AB - BACKGROUND: Gingival hyperpigmentation is a common esthetical concern in patients with gummy smile or excessive gingival display. Laser ablation has been recognized recently as the most effective, pleasant and reliable technique. It has the advantage of easy handling, short treatment time, hemostasis, decontamination, and sterilization effect. AIM: In the present study we wanted to explore the efficacy of a 980 nm wavelength diode laser in gingival depigmentation clinically by using both VAS and digital imaging method as means of assessment. METHODS: Diode laser ablation was done for 15 patients who requested cosmetic therapy for melanin pigmented gums. The laser beam delivered by fiberoptic with a diameter of 320 um, the diode laser system has 980 nm wave lengths and 3 W irradiation powers, in a continuous contact mode in all cases, the entire surface of each pigmented maxillary and mandibular gingiva that required treatment was irradiated in a single session. Clinical examination and digital image analysis were done and the patients were followed up for 3 successive months. RESULTS: There was a statistically significant change in prevalence of bleeding after treatment, as none of the cases showed any signs of bleeding 1 week, 1 month and 3 months after ablation. No statistically significant change was observed in the prevalence of swelling after treatment The VAS evaluation demonstrated that only 4 patients complained of mild pain immediately after the procedure. No pain was perceived from the patients in the rest of the follow up period. There was no statistically significant change in prevalence of pain immediately after treatment compared to pain during treatment. There was a decrease in cases with mild pain after 1 week, 1 month as well as 3 months compared to pain during treatment and immediately after treatment. CONCLUSION: Within the limitations of this study, the use of diode laser was shown to be a safe and effective treatment modality that provides optimal aesthetics with minimal discomfort in patients with gingival hyperpigmentation. PMID- 27275270 TI - The Biomechanical Effect of Different Denture Base Materials on the Articular Disc in Complete Denture Wearers: A Finite Element Analysis. AB - AIM: The objective of the present study was to evaluate the effect of different denture base materials on the stress distribution in TMJ articular disc (AD) in complete denture wearers. MATERIAL AND METHODS: A three dimensional Finite Element (FEA) models of an individual temporomandibular joint (TMJ) was built on the basis CT scan. The FEA model consisted of four parts: the condyle, the articular disc, the denture base, and the articular eminence skull. Acrylic resin and chrome-cobalt denture base materials were studied. Static loading of 300N was vertically applied to the central fossa of the mandibular second premolar. Stress and strain were calculated to characterize the stress/strain patterns in the disc. RESULTS: The maximum tensile stresses were observed in the anterior and posterior bands of (AD) on load application with the two denture base materials. The superior boundaries of the glenoid fossa showed lower stress than those on the inferior boundaries facing the condyle. CONCLUSIONS: Within the limitations of the present study it may be concluded that: The denture base material may have an effect in stress-strain pattern in TMJ articular disc. The stiffer denture base material, the better the distribution of the load to the underling mandibular supporting structures & reducing stresses induced in the articular disc. PMID- 27275271 TI - A Comparative Evaluation of Low-Level Laser and Topical Steroid Therapies for the Treatment of Erosive-Atrophic Lichen Planus. AB - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease that causes bilateral white striations, papules, or plaques on the buccal mucosa, tongue, and gingivae. Erythema, erosions, and blisters may or may not be present. Several empirical therapies have been used in the treatment of (OLP). OBJECTIVE: To evaluate the effect of low level laser therapy (LLLT) versus topical steroids for the treatment of erosive-atrophic lichen planus. SUBJECTS AND METHODS: Twenty four patients with erosive-atrophic (OLP) were categorized into two groups. In the first group patients were treated with 970 nm diode laser irradiation, while, in the second group patients used topical corticosteroids (0.1% triamcinolone acetonide orabase). The gender, medical history and pain score were recorded. The pain score was measured before and after treatment by visual analogue scale (VAS). RESULTS: Steroid-treated group (0.1% triamcinolone acetonide orabase) show reduced pain score than laser group. CONCLUSION: Topical steroids are more effective than LLLT. LLLT may be used as an alternative treatment for symptomatic OLP when steroids are contraindicated. PMID- 27275272 TI - Serum Levels of Copper, Ceruloplasmin and Angiotensin Converting Enzyme among Silicotic and Non-Silicotic Workers. AB - BACKGROUND: Silicosis is the most frequently occurring pneumoconiosis. AIM: Measurement of serum levels of Angiotensin converting enzyme (ACE), Copper (Cu) and Ceruloplasmin (Cp) in cement workers occupationally exposed to silica dust as biomarkers of exposure rather than biomarkers of effect for silicosis. METHODS: Plain chest X-ray & pulmonary functions were done for 30 silicotic and 42 non silicotic workers and 42 controls. CT scan was done for the exposed groups. Serum levels of Cu, Cp and ACE were estimated. RESULTS: The results showed a higher significant difference between the exposed groups and controls, and between the two exposed groups regarding the mean levels of all measured biochemical parameters. The pulmonary functions were significantly lower among silicotic workers than controls and non-silicotic groups. There was a significant positive correlation between duration of employment and serum ACE and Cu. CONCLUSION: Since respirable dust exposure-linked lung fibrosis disease is non-curable, the biochemical parameters (Cu, ACE and Cp) can be used as exposure biomarkers to silica dust, providing a better way for early diagnosis of this deadly disease. Down regulating the inflammatory responses could potentially reduce the adverse clinical pulmonary effects of air pollution. PMID- 27275273 TI - The Health Status of the Reproductive System in Women Living In the Aral Sea Region. AB - In order to assess women's reproductive health in the Kyzylorda region (the Aral Sea) of Kazakhstan, 1406 women were involved in an integrated clinical-functional and laboratory examination, given regional and environmental ecological factors. The high level of endocrine gynecological pathology is indicated in the examined women. In both examined zones, there is a late menarche over 16 years old, which is 39%. It is indicated a trend towards younger age of menopause onset. Inflammatory diseases of the female genital organs affect a third of the examined women. In the zone of ecological disaster, every fourth woman has fetal losses, cases of spontaneous pregnancy termination and/or non-developing pregnancies in anamnesis, which can be repeated many times. PMID- 27275274 TI - Reliability, Validity and Factor Structure of the 12-Item General Health Questionnaire among General Population. AB - AIM: The aim of the study is to analyze the internal consistency; validity and factor structure of the twelve item General Health Questionnaire for the Macedonian general population. MATERIAL AND METHODS: Data came from nationally representative sample of 1603 randomly selected Macedonians all aged 18 years or older. RESULTS: The mean GHQ score in the general sample was found to be 7.9 (SD = 4.3). The results revealed a higher GHQ score among women (M = 8.91, SD = 4.5) compared to men (M = 6.89; SD = 4.2). The participants from the rural areas obtained a lower GHQ score (M = 7.55, SD = 3.8) compared to participants coming from the urban areas (M = 9.37, SD = 4.1). The principal component analysis with oblique rotation (direct oblimin) with maximum likelihood procedure solution was performed and the results yielded a three factor solution which jointly accounted for 57.17% of the total variance: Factor I named social management (items 1, 3, 4, 6, 7 and 8); Factor II stress (items 2, 5 and 9) and Factor III named self confidence (items 10, 11 and 12). Its factor structure is in line with representative research from other population groups. CONCLUSION: The GHQ-12 can be used effectively for assessment of the overall psychological well-being and detection of non-psychotic psychiatric problems among the Macedonian population. PMID- 27275275 TI - Level of Work Related Stress among Teachers in Elementary Schools. AB - BACKGROUND: Teaching is considered a highly stressful occupation, with work related stress levels among teachers being among the highest compared to other professions. Unfortunately there are very few studies regarding the levels of work-related stress among teachers in the Republic of Macedonia. AIM: To identify the level of self-perceived work-related stress among teachers in elementary schools and its relationship to gender, age, position in the workplace, the level of education and working experience. MATERIAL AND METHODS: We performed a descriptive-analytical model of a cross-sectional study that involved 300 teachers employed in nine elementary schools. Evaluation of examined subjects included completion of a specially designed questionnaire. RESULTS: We found that the majority of interviewed teachers perceive their work-related stress as moderate. The level of work-related stress was significantly high related to the gender, age, position in workplace, as well as working experience (p < 0.01), while it was significant related to level of education (p < 0.05). Significantly greater number of lower-grade teachers perceives the workplace as extremely stressful as compared to the upper-grade teachers (18.5% vs. 5.45%), while the same is true for female respondents as compared to the male ones (15.38% vs. 3.8%). In addition, our results show that teachers with university education significantly more often associate their workplace with stronger stress than their colleagues with high education (13.48% vs. 9.4%). We also found that there is no significant difference of stress levels between new and more experienced teachers. CONCLUSION: Our findings confirm that the majority of interviewed teachers perceived their work-related stress as high or very high. In terms of the relationship between the level of teachers' stress and certain demographic and job characteristics, according to our results, the level of work-related stress has shown significantly high relation to gender, age, levels of grades taught as well as working experience, and significant relation to the level of education. PMID- 27275276 TI - Disturbance of Antioxidant Enzymes and Purine Metabolism in the Ejaculate of Men Living in Disadvantaged Areas of Kyzylorda Region. AB - AIM: Objective of the study was to evaluate the state of the main indicators of antioxidant status and enzymes of purine metabolism in the germ cells of men living in the zone of ecological catastrophe Aral Sea region. METHODS: The criterion for inclusion is the stay of an adult in the Aral Sea area is not less than 5 years, employment in occupations with no more than 2 hazard class. Determination of the activity of adenosine deaminase (ADA) was conducted in semen by the method of Nemechek et al., 1993. Determination of the activity of catalase (CAT) was performed according by the method of Korolyuk et al., 1988. RESULTS: Results of the study indicate a change in the activity of catalase and adenosine deaminase, due to increased levels of oxidative stress and the development of the pathological process. CONCLUSIONS: According to the results of study, it was put the influence of negative factors of the Aral Sea region in men's sperm of reproductive age gives to disability free-radical processes, that proves changing of ferments of ant oxidative protection Catalase and adenosine deaminase (ADA). This disturbance in men's sperm of reproductive age leading to increased level of oxidative stress and impaired activity of antioxidant enzymes and purine metabolism, responsible for the abnormal transmembrane and intracellular processes, reflecting the degree of imbalance of enzymes. PMID- 27275277 TI - Stress Causing Factors Among Teachers in Elementary Schools and Their Relationship with Demographic and Job Characteristics. AB - BACKGROUND: Once high levels of work-related stress among teachers were confirmed many studies concentrated on identifying and investigating key stress factors among school teachers. Unfortunately there are very few researches made on stress causing factors among teachers in Republic of Macedonia. AIM: To determine the most frequent stress causing factors among teachers in elementary schools and to investigate their relationship with demographic and job characteristics. METHODOLOGY: We performed a descriptive-analytical model of a cross-sectional study which involved 300 teachers employed in nine elementary schools. Evaluation of examined subjects included completion of a specially designed questionnaire. RESULTS: Among six categories of factors that generate work related stress (job demands, control, relationships, role, changes and support) control and support had the highest mean scores. Within the control category the highest levels of perceived teacher's work-related stress were caused by the following factors - changes in terms and conditions without consultation and given responsibility without the authority to take decisions. 141 out of the interviewed teachers (47%) have mentioned changes in terms and conditions without consultation as very stressful, while another 50 (16.67%) have reported it as stressful. 123 out of interviewed teachers (41%) have stated given responsibility without the authority to take decisions as very stressful, with another 105 (35%) have reported it as stressful. In the category support the highest levels of perceived teacher's work related stress were caused by stress factors - lack of funds/resources to do the job and limited or no access to training. Out of 300 interviewed teachers, 179 (59.67%) have reported lack of funds/resources to do the job as very stressful, while another 50 (16.67%) as stressful. There is no significant relationship between the stress factor limited or no access to training and demographic and job characteristics. CONCLUSION: Our findings confirm that within the control category, the highest levels of perceived teacher's work-related stress were caused by changes in terms and conditions without consultation and given responsibility without the authority to take decisions, while in the category support, the same was true for stress factors lack of funds/resources to do the job and limited or no access to training. We have also concluded that the lower grade school teachers, female teachers, teachers for whom this is the first job and teachers with university education perceive more often the lack of authority to take decisions as a very stressful factor than the upper-grade school teachers, male teachers, teachers previously employed in another workplace, and those with high education. The lower-grade school teachers, older teachers and teachers with university education perceive more often changes in education as a very stressful factor than the upper grade school teachers, younger teachers and those with high education. PMID- 27275278 TI - Respiratory Symptoms and Lung Function in Never-Smoking Male Workers Exposed To Hardwood Dust. AB - BACKGROUND: Results from many studies suggest that workplace exposure to organic dust may lead to adverse respiratory effects in exposed workers. AIM: In order to assess the respiratory effects of the workplace exposure to hardwood dust we performed a cross-sectional study of never-smoking male workers employed in parquet manufacture and never-smoking male office workers as a control. MATERIAL AND METHODS: We performed a cross-sectional study including 37 never-smoking male workers employed in parquet manufacture and an equal number of never-smoking male office workers studied as a control. Evaluation of examined subjects included completion of a questionnaire for respiratory symptoms in the last 12 months and baseline spirometry performed according to the actual recommendations. RESULTS: We found a higher prevalence of respiratory symptoms in parquet manufacturers than in office workers with significant difference for cough and phlegm. Majority of the respiratory symptoms in the parquet manufacturers were work-related. The mean values of all spirometric parameters with exception of forced ventilatory capacity (FVC) were significantly lower in the parquet manufacturers as compared to their mean values in the office workers. We found close relationship between both the prevalence of respiratory symptoms and the reduction of spirometric parameters in the parquet manufacturers and the duration of the workplace exposure to wood dust. CONCLUSION: Our data suggest that workplace exposure to hardwood dust may lead to adverse respiratory effects indicating the need of adequate preventive measures in order to protect the respiratory health of exposed workers. PMID- 27275279 TI - Burnout, Engagement, and Organizational Culture: Differences between Physicians and Nurses. AB - BACKGROUND: Burnout results from a prolonged response to chronic emotional and interpersonal workplace stressors. The focus of research has been widened to job engagement. AIM: Purpose of the study was to examine associations between burnout, job engagement, work demands, and organisational culture (OC) and to demonstrate differences between physicians and nurses working in general hospital in Skopje, Republic of Macedonia. MATERIAL AND METHODS: Maslach Burnout Inventory and Utrecht Work Engagement Scale were used for assessment of burnout and job engagement. Work demands and OC were measured with Hospital Experience Scale and Competing Values Framework, respectively. RESULTS: Higher scores of dedication, hierarchy OC, and organizational work demands were found in physicians. Nurses demonstrated higher scores of clan OC. Burnout negatively correlated with clan and market OC in physicians and nurses. Job engagement positively correlated with clan and market OC in nurses. Different work demands were related to different dimensions of burnout and/or job engagement. Our findings support job demands resources (JD-R) model (Demerouti and Bakker). CONCLUSIONS: Data obtained can be used in implementation of specific organizational interventions in the hospital setting. Providing adequate JD-R interaction can lead to prevention of burnout in health professionals (HPs) and contribute positively to better job engagement in HPs and higher quality of patient care. PMID- 27275280 TI - Quality of Life of the Health Care Workers in the Pre-Retirement Period from the Private Sector of the Primary Health Care from the Skopje Region. AB - BACKGROUND: The quality of life (QOL) of the workers in the pre-retirement period is an important line in their functioning, as well as in the process of their preparing for retirement. AIM: To assess the QOL of the health care workers - HCW (doctors and nurses/medical technicians) in the pre-retirement period from the private sector of the Primary Health Care (PHC). MATERIAL AND METHODS: We performed a cross-sectional, questionnaire-based study including 200 HCW in their pre-retirement period from the PHC from the Skopje region divided in two groups. The examined group (EG) included 100 HCW working in the private sector, whereas the control group (CG) consisted of 100 HCW employed in the public sector, matched to EG by age and duration of employment at the actual workplace. The QOL of the examinees was assessed by the World Health Organization Quality of Life - Bref questionnaire (WHOQOL - BREF). RESULTS: Examinees from both group assessed their QOL as good, i.e. there was no significant difference between the mean scores of EG and CG in regard to assessment of their QOL (3.7 vs. 3.6; p = 0.274). Regarding the satisfaction with their health, we found that examinees from EG are significantly more satisfied with their health than the examinees of CG as it was expressed by the obtained mean scores (3.9 vs. 3.6; p = 0.017). The mean scores of the domain assessing physical health and environment did not differ significantly between EG and CG (23.4 vs. 22.9; p = 0.187 and 25.7 vs. 24.9; p = 0.290, respectively). We found significant difference between EG and CG in regard to the mean scores assessing the psychological health (23.1 vs. 21.5; p = 0.003) and social life (11.6 vs. 10.1; p < 0.001). CONCLUSION: HCW from EG evaluated their QOL slightly better and they were more satisfied with their health than HCW from CG. In addition, HCW from EG assessed better their psychological health and social life than HCW from CG, whereas regarding the assessment of the physical health and environment, there was no difference between two groups. PMID- 27275281 TI - Heart Failure with Preserved Ejection Fraction - Concept, Pathophysiology, Diagnosis and Challenges for Treatment. AB - Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) occurs in 40 to 60% of the patients with HF, with a prognosis which is similar to HF with reduced ejection fraction (HFrEF). HFpEF pathophysiology is different from that of HFrEF, and has been characterized with diastolic dysfunction. Diastolic dysfunction has been defined with elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filing and elevated LV end diastolic pressure. Arterial hypertension occurs in majority cases with HFpEF worldwide. Patients are mostly older and obese. Diabetes mellitus and atrial fibrillation appear proportionally in a high frequency of patients with HFpEF. The HFpEF diagnosis is based on existence of symptoms and signs of heart failure, normal or approximately normal ejection and diagnosing of LV diastolic dysfunction by means of heart catheterization or Doppler echocardiography and/or elevated concentration of plasma natriuretic peptide. The present recommendations for HFpEF treatment include blood pressure control, heart chamber frequency control when atrial fibrillation exists, in some situations even coronary revascularization and an attempt for sinus rhythm reestablishment. Up to now, it is considered that no medication or a group of medications improve the survival of HFpEF patients. Due to these causes and the bad prognosis of the disorder, rigorous control is recommended of the previously mentioned precipitating factors for this disorder. This paper presents a universal review of the most important parameters which determine this disorder. PMID- 27275282 TI - Letter to the Editor: Orthostatic Reactivity in Patients with Ischemic Stroke in the Chronic Period. OA Maced J Med Sci. http://dx.doi.org/10.3889/oamjms.2015.090. PMID- 27275283 TI - Errata Corrige. Orthostatic Reactivity in Patients with Ischemic Stroke in the Chronic Period. http://dx.doi.org/10.3889/oamjms.2015.090. AB - AIM: This study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on orthostatic reactivity in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: An active orthostatic test is used for the evaluation of the orthostatic reactions. The arterial blood pressure and heart rate were defined in the 10 minutes of supine position, before and after 1, 5 and 10 minutes of active upright position. The orthostatic autoregulation is evaluated four times - at the beginning of the study, on the 10th day, on the 1st month and three months after the start of the KT. The classification by Thulesius was used to separate the patients into two groups depending on the type of their orthostatic reactivity. RESULTS: At the beginning of the study of infringements symptomatic type orthostatic reactivity (SOR) was observed in 24 patients and hypertensive type orthostatic reactivity (HOR) was observed in the remaining 32 patients. Once applied SKTM establish improvement of orthostatic autoregulation for the groups SOR and HOR at the 10th day and the 1st month with a level of significance p <0.05. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as an adapted exercise program at home, has significantly improved the orthostatic reactivity in patients with orthostatic dysregulation due to the ISChP. PMID- 27275284 TI - DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors. AB - BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID- 27275285 TI - Lamivudine-Induced Liver Injury. AB - BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention. AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine. MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10 day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), gamma-glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05. RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses >= 100 mg/kg. CONCLUSION: Lamivudine toxicity in rat liver appeared to be mediated by oxidative stress. PMID- 27275286 TI - Dysplasia in Gastric Mucosa and its Reporting Problems. AB - BACKGROUND: The recognition, terminology used and histopathologic evaluation of two essential elements in gastric carcinogenesis, atrophy and dysplasia, are characterized by controversy. MATERIALS AND METHODS: One hundred fifteen cases, with slides and their histopathologic reports from the archive of the Laboratory of Pathology were studied for the diagnostic value, reporting of dysplasia, interobserver variability, the relation of dysplastic lesions with inflammation, atrophy and metaplasia. After retrospectively studying the histopathologic reports from the archive we distributed the cases according to endoscopic and histopathologic diagnosis, together with the reexamination of the slides. The comparison of the median values of the numeric variables was made with the Mann Whitney test (non-parametric equivalent of the Student's "t" test). RESULTS: The endoscopic clinical diagnosis were: malignancy/suspicious for malignancy 88 cases (76%) and non-neoplastic diagnosis (like ulcer or gastritis) 27 cases (24%). From the reexamination of the cases it resulted that there is no difference in reporting the malignancy, but there is a difference in the cases reported as dysplasia (p = 0.001) and negative for neoplasia (p = 0.063, borderline). CONCLUSION: Clinicians and pathologists can feel directly the discrepancy called "interobserver variability" and should be assured that the use of guidelines will cause a lowering of this variability. PMID- 27275287 TI - Neck Circumference as a Predictor of Adiposity among Healthy and Obese Children. AB - BACKGROUND: Obesity, particularly in the upper part of body, is a major health problem. Because body mass index (BMI) does not adequately describe regional adiposity, other indices of body fatness are being explored. OBJECTIVES: To determine if neck circumference is a valid measure of adiposity (fat distribution) among group of Egyptian children. SUBJECTS AND METHODS: This is a cross sectional study, included 50 obese subjects, aged 7 - 12 years recruited from Endocrine, obesity and Metabolism Pediatric Unit at Children Hospital, Cairo University and 50 healthy children, age and sex matched. All children were subjected to blood pressure assessment (systolic SBP and diastolic DBP), and anthropometric assessment (body weight, height, neck circumference (NC), waist (WC) and hip (HC) circumferences, and skin fold thicknesses at three sites: biceps, triceps and sub scapular. BMI [weight (kg)/height (m2)] was calculated. RESULTS: In healthy females, significant associations were detected between NC and SBP, DBP and all anthropometric measurements. However, in healthy males NC was not significantly associated with BMI, SBP and DBP. In the obese group; both sexes; insignificant association was found between NC and SBP, DBP, BMI and skinfold thickness. CONCLUSION: NC is related to fat distribution among normal healthy female children. However, this relation disappears with increasing adiposity. The results do not support the use of NC as a useful screening tool for childhood obesity. PMID- 27275288 TI - Adipokines Vaspin and Visfatin in Obese Children. AB - BACKGROUND: Adipokines provides new insights about the physiology, pathology and treatment of obesity. AIM: We investigated the association between serum vaspin and serum visfatin concentrations with obesity in Egyptian children. MATERIAL AND METHODS: Twenty two obese children with body mass index (BMI) above 95th percentile; 11 males and 11 females were included in this study. Their mean age was 9.18 +/- 2.8 years. After general clinical examination, fasting blood glucose, triglycerides, total cholesterol and high density lipoprotein cholesterol were measured in cases and controls (n=11). Fasting insulin, vaspin and visfatin were detected using ELIZA. Insulin resistance was estimated by Homeostasis model assessment method (HOMA-IR). RESULTS: Blood pressure, in both systolic and diastolic measurements was elevated significantly in obese children. Significant elevation of serum insulin and insulin resistance (HOMA/IR) were observed in obese children too. Vaspin and visfatin showed significant elevation in obese children than controls. Significant positive correlations were detected between visfatin and BMI, waist circumference, hip circumference and HOMA/IR. We found that Vaspin and visfatin are higher in obese children. CONCLUSION: Visfatin but not vaspin correlates positively with waist circumference and HOMA/IR in obese children. PMID- 27275289 TI - Amelioration of Cadmium-Induced Nephropathy using Polyphenol-rich Extract of Vernonia amygdalina (Del.) Leaves in Rat Model. AB - AIM: To determine the effects of polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA) in rats with Cd-induced nephropathy. MATERIALS AND METHODS: Sixty five male Wistar rats were divided into five groups as follows; Group 1 received distilled water throughout the period of study. Group 2 received 5 mg/kg body weight of cadmium (Cd), in the form of CdSO4, for five consecutive days via intraperitoneal route. Groups 3, 4 and 5 were pretreated with Cd as group 2 and thereafter received oral treatment of PEVA for 4 weeks at 100 mg/kg, 200 mg/kg and 400 mg/kg body weight, respectively. RESULTS: Exposure to Cd toxicity significantly induced deleterious alterations in plasma and urine levels of creatinine, urea and glucose as well as creatinine and urea clearance (p < 0.05) in the rat model. There was a significant disturbance in the antioxidant system as revealed by the levels of thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH) (p < 0.05) in the kidney tissue of the rats. With marked improvements in renal histoarchitecture, PEVA treatment showed a duration and non dose-dependent ameliorative potential. CONCLUSION: PEVA treatment reversed the compromise of renal function that was induced by Cd toxicity in rat model. PMID- 27275290 TI - Association of Neck Circumference with Obesity in Female College Students. AB - BACKGROUND: Obesity levels have been dramatically increased in the United Arab Emirates over the last few years. High levels of body Mass Index, waist circumference, and percent of total body fat as a measure of obesity have found to be related to cardiovascular risk factors and other diseases. Neck circumference is a new tool that has been linked to obesity. However, no studies in UAE have been conducted yet. AIM: The purpose of this study was to measure the obesity levels in a college population and to correlate them with NC and other anthropometrical indexes. METHODS AND SUBJECTS: Two hundred forty three (243) female students aged 18-25 were conveniently selected to participate in the study. Anthropometrical indexes were obtained from all subjects e after fasting. RESULTS: The prevalence of overweight and obesity together was found to be 28.4 % (n = 69). Pearson correlation showed that WC, NC and BF (%) were significantly positively related to obesity, (r = 0.790; r = 0.758; r = 0.767, p < 0.001), respectively. In multiple regression analysis, only NC (Beta: 1.627, 95 %CI: 0.370, 2.846, p < 0.001) and WC (Beta: 0.464, 95 %CI: 0.135, 0.664, p < 0.001) were found to be independently associated with obesity. CONCLUSION: NC was found to be independently associated with obesity levels in Emirati college students. PMID- 27275291 TI - Biochemical Assessment of Bone Health in Working Obese Egyptian Females with Metabolic Syndrome; the Effect of Weight Loss by Natural Dietary Therapies. AB - AIM: To investigate the relation between bone parameters and the metabolic syndrome criteria, before and after the administration of two different natural dietary supplements in middle aged working obese Egyptian women suffering from metabolic syndrome (MetS). SUBJECTS AND METHODS: Fifty eight middle aged obese female volunteers suffering from metabolic syndrome were divided into two groups. During the first period, group (A) consumed a low caloric diet and nutritional supplement consisting of doum flour biscuits, while group (B) consumed whole meal wheat flour biscuit with the same instructions. During the second period, both supplements were omitted. Assessment of blood pressure, relevant anthropometric parameters, lipid accumulation product, fasting blood glucose, uric acid, 25 hydroxy vitamin D (25 (OH) D), parathyroid hormone (PTH) and bone-specific alkaline phosphatase were performed. RESULTS: Data showed that although both supplements improved the MetS criteria and the bone health parameters, the supplement containing the doum flour proved to be more effective. CONCLUSION: These results confirm the benefit of doum in improving bone health parameter [25 (OH) D/PTH axis] in the MetS patients, beside the MetS criteria. So, we can conclude that natural effective supplements lead towards the optimization of biochemical parameters in favor of a healthy outcome. PMID- 27275292 TI - Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption. AB - BACKGROUND: Factor V Leiden, Prothrombin and MTHFR gene mutation, could have an influence in pregnancy with adverse outcome Preeclamsia, IUGR and Placental abruption. AIM: The aim of this study is to investigate the presence of above mentioned inherited thrombophilias and its statistical significance, distribution among the complicated and normal pregnancy, and relative risk for carrier of mutation to develop preeclampsia, IUGR and placental abruption. MATERIAL AND METHODS: Prospective cohort study is implemented at University Clinic for Obstetric and Gynecology in Skopje, Republic of Macedonia. The study included 109 delivered patients: 40 with preeclapmsia, 22 with IUGR, 17 with placental abruption and 30 as control group with normal pregnancy. The amount of 3 ml venous blood has been used for detection of these point mutations using ThromboStrip -Opegen, QIAGEN kit manufactured for thrombotic risk. RESULTS: The highest frequency was found: in the group with preeclampsia 35% were MTHFR homozygous, IUGR -MTHFR heterozygous 45%, Placental abruption- 52.9% MTHFR heterozygous, and in the control group without thrombophilia 56.7%. There were combined thrombophilia in 3 patients. There aren't statistical significance in presence of thrombophilia among groups (p > 0.05). Statistical significance (p < 0.05) was found between carriers of MTHFR homozygous in preeclampsia and group with placental abruption and control group. Relative risk in IUGR group for MTHFR homozygous was 5.54 (1.37= 6.5%), controlled (<7%) and uncontrolled (>=7%) known DM. RESULTS: 150 patients, (93 male and 57 female) were included. Impaired glucose metabolism was detected in 44.5% of patients, 7.9% of whom were newly-diagnosed DM. The highest levels of stress glycaemia were found in new and uncontrolled known DM. The in hospital event rate was 20.7%, the mortality rate 7.3%, being the highest in new diagnosed and uncontrolled known DM patients. CONCLUSIONS: The prevalence of unknown DM was high among patients with ACS. Stress glycaemia and failure to achieve glycemic controlee, were an independent predictors of in-hospital cardiac events. PMID- 27275296 TI - Study of Adiponectin Level in Diabetic Adolescent Girls in Relation to Glycemic Control and Complication of Diabetes. AB - AIM: To study the relation between adiponectin level with glycemic control and complication of diabetes. PATIENTS AND METHODS: The study included 40 female adolescent type 1 diabetic patients and 40 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile and adiponectine. Urine sample was taken for assessment of albumin/creatinine ratio. RESULTS: Diabetic patients had a significantly higher diastolic blood pressure, triglyceride, total cholesterol, LDL and adiponectin than controls. Patients with diabetes complication had a significant lower BMI and HDL. On the other hand, they had higher disease duration, total cholesterol, HbA1, albumin/creatinine ratio and adiponectin. Patients with microalbuminuria had a lower BMI, higher disease duration, diastolic blood pressure and adiponectin. Patients with diabetic retinopathy had higher disease duration, insulin dose, HbA1, microalbuminuria and adiponectin. Adiponectin in diabetic patients had a significant negative correlation with BMI and positive correlation with systolic blood pressure and microlabuminuria. CONCLUSION: Serum adiponectin level is high in adolescent type 1 diabetic girls. It can be used as a predictor of diabetes complications rather than a sensitive biochemical marker for glycemic control. PMID- 27275297 TI - Influence of Kinesitherapy on Gait in Patients with Ischemic Stroke in the Chronic Period. AB - AIM: The study aims to trace the influence of specialized kinesitherapeutic methodology (SKTM) on gait in patients with ischemic stroke in the chronic period (ISChP). MATERIAL AND METHODS: The study was conducted with 56 patients with ISChP (duration of the disease up to 1 year). For determining changes in gait before and after the treatment a cadence of gait and maximum movement speed were taken into consideration. To determine the cadence, steps are counted for covering 6 meters and 10 meters respectively. The maximum speed of the gait is determined in m / min by dividing undergone distance (m) and time (min). RESULTS: Patients were found to significantly normalize the parameters of gait. Compared to the initial data, there is a significant reduction in the number of steps on 6 and 10 meters and a tendency to increase the speed of gait, with the significant change during the 1st month with a level of significance of p <0.001. CONCLUSION: The applied specialized kinesitherapeutic methodology continued later as exercise program at home, which significantly improved gait cadence and speed of movement in patients with ischemic stroke in the chronic period and is with a supportive prolonged exposure. PMID- 27275298 TI - Incidence and Impact of Patient-Prosthesis Mismatch in Isolated Aortic Valve Surgery. AB - AIM: The mains topics of this work are the incidence of patient-prosthesis mismatch and the influence in the early results of isolated aortic valve surgery. METHODS: In 193 patients isolated aortic valve surgery was performed. The study population was divided in three subgroups: 20 patients with severe, 131 patients with moderate and 42 patients without patient-prosthesis mismatch. The indexed effective orifice area was used to define the subgroups. Operative mortality and perioperative complications were considered the indicators of the early results of aortic valve surgery. RESULTS: The incidence of severe and moderate patient prosthesis mismatch was respectively 10.3% and 67.8%. Hospital mortality and perioperative complications were: mortality 5% vs. 3.1% vs. 2.4% (p = 0.855), low cardiac output 5% vs. 6.9% vs. 4.8% (p = 0.861); pulmonary complications 5% vs. 3.1 vs. 0.0% (p = 0.430); exploration for bleeding 5% vs. 0.8% vs. 2.4% (p = 0.319); atrial fibrillation 30% vs. 19.8% vs. 11.9% (p = 0.225); wound infection 5% vs. 0.8% vs. 0.00% (p = 0.165), respectively for the group with severe, moderate and without patient-prosthesis mismatch. CONCLUSIONS: Patient-prosthesis mismatch is a common occurrence in aortic valve surgery. This phenomenon does not affect the early results of aortic valve surgery. PMID- 27275299 TI - Role and Significance of Markers of Inflammation in the Asthmatic Disease. AB - BACKGROUND: Asthma is characterized by airway inflammation which can be reversible. AIM: Investigation the importance of eosinophils, ECP and IL-5 in asthmatics versus patients with obstructive bronchitis and healthy subjects. We investigated the values before and after the treatment in asthmatics. MATERIAL AND METHODS: We studied 77 subjects divided in three groups as follows: 1) asthma patients; 2) patients with obstructive bronchitis and 3) control group of healthy subjects. In all the subjects there were determined: Total number of eosinophils (Eo), eosinophilic cationic protein (ECP), Interleukin 5 (IL-5) and allergy tests. RESULTS: The total number of eosinophils was significantly increased in the group of asthma patients versus second and third group. We found that the presence of ECP demonstrate an ongoing inflammation, with or without clinical symptoms of asthma patients. There was significant difference between the values of ECP of asthma patients versus second and third group. Our results have shown that IL-5 was significantly increased versus second group and controls (p < 0.01). We also found the decrease of the values of inflammatory markers after the treatment with corticosteroids. CONCLUSIONS: Eosinophils, ECP and IL-5 could be useful markers for selecting allergic patients and could be the monitors of treatment effects. PMID- 27275300 TI - Psychological Patient Reactions after Septorhinoplasty - Our Personal View. AB - AIM: The aim of our study is to observe adequate and inadequate psychological reactions in patients who are candidates for septorhinoplasty, before and after surgery and to create an adequate psychological model of a person suitable for septorhinoplasty in this group of patients. MATERIAL AND METHODS: In this study, 140 patients with nasal septal deviation (deviatio septi nasi), alone or together with other nasal deformities, were observed in the period of 4 years (2011-2015 year). Our patients were psychologically observed using two standard psychological tests: Patients selection for septorhinoplasty and their psychological abilities ("Self-body image" questionnaire) and Brief Symptom Inventory (BSI) test. RESULTS: Most of the patients 43 (39.8%), thought that after rhinoseptoplasty their self-confidence arise, 32 (29.63%) expected changing's in their life's, few of them 9 (8, 3%) thought that the environment will act different with them. The Brief Symptom Inventory (BSI) in women group was shown that most of the women patients presented symptoms of somatisation; 23 (23.33%) and 15 (25%) one year after surgery. CONCLUSIONS: The patients made a sound decision for intervention, which was useful for the surgeon too, because it helped them choose an adequate operative technique and especially helped them in the postoperative period. PMID- 27275301 TI - Clinical Significance of Serum IL-12 Level in Patients with Early Breast Carcinoma and Its Correlation with Other Tumor Markers. AB - AIM: To investigate the diagnostic significance of Interleukin 12 (IL-12) in breast cancer (BC) and its correlation with other tumor markers including cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MMP9/TIMP1 ratio. METHODS: Serum levels of IL-12, tumor markers, and hormone receptors were measured in 92 BC and 56 benign lesion patients versus 40 healthy subjects. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were recorded. RESULTS: BC patients have lower IL-12, but higher CA 15.3 and CEA than control group. High levels of serum IL-12 were associated with lymph node positivity and progesterone receptor negativity. IL-12 was significant lower in invasive ductal carcinoma (IDC) compared to non IDC histological type. IL-12 was higher in patients with higher stage and grade but the difference was not statistically significant. IL-12 correlates negatively with MMP9/TIMP1 ratio. CONCLUSION: IL-12 is less specific than CEA for screening early BC, but its correlation with tumor aggressiveness and progression markers may have a prognostic value. PMID- 27275302 TI - Evaluation of Clinicopathological and Risk Factors for Nonmalignant H. Pylori Associated Gastroduodenal Disorders in Iraqi Patients. AB - AIM: To determine the risk factors associated with H. pylori infection and possible correlation with clinicopathological parameters. MATERIAL AND METHODS: Gastroduodenal biopsies were examined by rapid urease test and Gram staining. Cag A cytotoxin was detected by in situ hybridization. RESULTS: Risk of H. pylori acquisition reported as following: Males have 1.38 fold, rural residents have 0.63 fold, Nonsmokers have 0.39 fold, mild smokers have 18 fold, and moderate smokers have 1.4 fold while heavy smokers have 1 fold. A person who's in contact with animals has 1.52 fold risks. Illiterates and patients with primary education have 5.36 & 3 fold risk respectively. Patients under proton pump inhibitor (PPI) therapy have 1.02 fold. Patients under NSAID therapy have 3.48 fold while nonalcoholic Patients have 0.75 fold. Patients using tap water have 0.45 fold risk. H. pylori infection positively correlated with age, weight loss, and heartburn. H. pylori inversely correlated with endoscopic diagnosis, Cag A positivity, and education level. Cag A positivity correlated with animal contact and NSAID usage. CONCLUSIONS: Several life style factors, education, animal contact, using of PPI, and NSAIDs increase the risk of H. pylori infection. Weight loss and heartburn cardinal signs for H. pylori infection. Endoscopic diagnosis and clinicopathological parameters not strictly associated with Cag A positivity. PMID- 27275303 TI - Predictive Factors for the Effect of Treatment by Noninvasive Ventilation in Patients with Respiratory Failure as a Result of Acute Exacerbation of the Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Noninvasive mechanical ventilation (NIV) applies ventilator support through the patient's upper airway using a mask. AIM: The aim of the study is to define factors that will point out an increased risk of NIV failure in patients with exacerbation of Chronic Obstructive Pulmonary Disease (COPD). PATIENTS AND METHODS: Patients over the age of 40, treated with NIV, were prospectively recruited. After data processing, the patients were divided into two groups: 1) successful NIV treatment group; 2) failed NIV treatment group. RESULTS: On admission arterial pH and Glasgow coma scale (GCS) levels were lower (pH: p < 0.05, GCS: p < 0.05), and Acute Physiology and Chronic Health Evaluation II (APACHE) score and PaCO2 were higher (p < 0.05) in the NIV failure group. Arterial pH was lower (p < 0.05) and PaCO2 and respiratory rate were higher (p < 0.05) after 1h, and arterial pH was lower (p < 0.05) and PaCO2 (p < 0.05), respiratory and heart rate were higher (p < 0.05) after 4h in the NIV failure group. CONCLUSION: Measurement and monitoring of certain parameters may be of value in terms of predicting the effectiveness of NIV treatment. PMID- 27275304 TI - Depression and Resilience in Breast Cancer Patients. AB - OBJECTIVE: A significant number of breast cancer patients, during their life with the diagnosis, experience emotional distress in the form of depression and anxiety. Psychological resilience is the ability of a person to protect his/her mental health when faced with adverse circumstances such as the cancer diagnosis. This study aims to assess the resilience in breast cancer patients and to explore whether depression affects the resilience. MATERIAL AND METHODS: Two hundred eighteen (218) women, treated for early breast cancer responded to Connor - Davidson Resilience Scale and Hospital Depression and Anxiety Scale, in order to assess the level of psychological resilience and the level of depression. RESULTS: There is a significant negative correlation between depression and resilience in our sample (r = - 0.562, p < 0.001). Individuals with higher levels of depression have lower levels of psychological resilience. There is no statistically significant correlation between the ages of the participants; time passed since diagnosis, cancer stage and resilience levels. CONCLUSION: This study shows that patients who are less depressed have higher levels of resilience and that psychological resilience may independently contribute to lower levels of depression among breast cancer patients. The level of psychological resilience may be a protective factor for depression and psychological distress. PMID- 27275305 TI - The Effect of Pre-Incision Field Block versus Post-Incision Inguinal Wound Infiltration on Postoperative Pain after Paediatric Herniotomy. AB - BACKGROUND: The Ilioinguinal/iliohypogastric nerve block has been shown to significantly decrease opioid analgesic requirements and side effects after inguinal herniotomy. We compared the effect of pre-incisional field block with 0.25% bupivacaine and post-incisional wound infiltration with 0.25% bupivacaine for postoperative pain control after inguinal herniotomy. PATIENTS & METHODS: This was a randomized controlled double blind study in 62 ASA I and II children aged 1-7 years scheduled for inguinal herniotomy. They were assigned to receive either pre-incision field block (group I) or post-incision wound infiltration at the time of wound closure (group II). The pain score was assessed in the recovery room using mCHEOPS score and VAS or FLACC score at home by the parents for 24 hours. RESULTS: The mean pain scores during the 2 hour stay in the recovery room, at 12 and 18 hours at home were similar in both groups, p > 0.05. However, the mean pain scores were significantly lower at 6 hours at home in group I (1.22 +/- 0.57) than in group II (1.58 +/-0.90), p <0.001, but significantly higher at 24 hours at home in group I (3.29 +/- 0.46) than in group II (2.32 +/- 0.24), p = 0.040. There was no difference in mean paracetamol requirement, and in the number of patients who required paracetamol for pain relief at home in both groups, p > 0.05. CONCLUSION: We have demonstrated that both pre-incisional ilioinguinal/iliohypogastric field block and post incisional wound infiltration provided adequate postoperative analgesia for 24 hours after inguinal herniotomy. PMID- 27275306 TI - Analysis of Plasma Concentrations of Theophylline in Smoking and Nonsmoking Patients with Asthma. AB - BACKGROUND: While dosing theophylline in asthmatics, we should consider that a lot of medicines, substances, conditions and diseases affect the clearance of theophylline, such as smoking, macrolide antibiotics, barbiturates, oral contraceptives, heart and liver insufficiency, alcohol, calcium-antagonists, pneumonia, viral infections, hypoxemia, etc. AIM: The aim of the study is to investigate the concentrations of theophylline during the day in smoking and nonsmoking patients with asthma. MATERIAL AND METHODS: We have estimated the concentrations of theophylline 6 times daily by the HPLC method (Keith Muir, J Chromatography) in 20 smoking and 20 nonsmoking asthmatic patients, who were treated with theophylline sustained-release tablets 175 mg twice daily. RESULTS: In the first group of 20 nonsmoking patients we obtained constant therapeutic and optimal concentrations of theophylline. In the second group of 20 smoking asthmatics the concentration of theophylline in plasma, in 8pm and 8am the next day was very low. CONCLUSION: Because in smokers we have increased clearance and the decreased half- life of theophylline, and in order to prevent the night time life-threatening attacks, it is necessary to recommend maximal doses of theophylline, especially in the evening. According to the study, dosage should be individualized in order to optimize the treatment based on the measurement of theophylline concentration in plasma. PMID- 27275307 TI - Glutathione Transferase as a Potential Marker for Gut Epithelial Injury versus the Protective Role of Breast Milk sIgA in Infants with Rota Virus Gastroenteritis. AB - BACKGROUND: Secretory immunoglobulin A (SIgA) plays an important protective role in the recognition and clearance of enteric pathogens. AIM: This study was designed to assess if mucosal integrity "measured by secretory IgA (SIgA)" is a protective factor from more epithelial alteration "measured by glutathione transferase" in infants with Rota gastroenteritis and its relation to infants' feeding pattern. PATIENTS AND METHODS: This study was conducted on 79 infants aged 6 months and less from those diagnosed as having gastroenteritis and admitted to Gastroenteritis Department in Abo El Rish Pediatric Hospital, Cairo University. Plasma glutathione s-transferases and Stool SIgA were measured using ELISA technique. Rota virus detection was done by Reverse transcriptase PCR. RESULTS: SIgA was found to be significantly positive in exclusive breast fed infants, Glutathione transferase was significantly more frequently positive in Rota positive cases than Rota negative cases by Reverse transcriptase PCR. A significant negative correlation between Glutathione transferase and Secretory IgA was found, (p < 0.05). CONCLUSION: Breast feeding should be encouraged and highly recommended in the first two years of life as it provides Secretory IgA to breast fed infants who in turn protect them against epithelial damage caused by Rota viral gastroenteritis. PMID- 27275308 TI - Cardiovascular Autonomic Neuropathy and Early Atherosclerosis in Adolescent Type 1 Diabetic Patient. AB - AIM: To evaluate cardiovascular autonomic neuropathy (CAN) in type 1 Diabetics and to detect its relation to coronary artery calcification. PATIENTS AND METHODS: It is a cross sectional study included 62 diabetics and 30 controls. Clinical, laboratory assessment and 24 Hr holter were done for all patients and controls and coronary artery calcium (CAC) scoring by multisclice CT was done for all patients only. T-test, Mann Whitney U test, and stepwise multiple regression were used for statistical analyses. RESULTS: CAC score was positive in 8.1 % of patients. Heart rate variability (HRV) was significantly lower in diabetics. All parameters of HRV were insignificantly lower in diabetics with positive CAC score. Patients with microalbuminuria had a significantly lower HRV. HRV had a significant correlation with age of patients, duration of disease, HbA1, and Qtc in diabetics. CONCLUSION: Percentage of arrhythmia and early atherosclerosis is high in adolescent type 1 diabetic patients. CAN is associated with early atherosclerosis. Cardiac autonomic neuropathy is associated with older age, longer duration, and poor glycemic control and microalbuminuria. PMID- 27275309 TI - Ultrasonographic Findings in Patients with Benign and Malignant Thyroid Nodules who underwent Ultrasound Guided Fine Needle Aspiration Cytology. AB - BACKGROUND: Patients with thyroid nodules represent common problem in daily routine of thyroidologists as well as other medical specialties. Fortunately only small number of thyroid nodules turns out to be malignant. Ultrasound is most frequently used imaging modality in the evaluation of thyroid nodules and certain ultrasonographic features are associated with greater risk for malignancy. AIM: The aim of our study was to evaluate the diagnostic performance of various ultrasonographic findings regarding thyroid malignancy. METHODS: Between September 2012 and August 2013 a total of 592 patients with 694 nodules were included in the present study. They were evaluated for thyroid nodules as a part of routine work up at outpatient's unit of Institute of Pathophysiology and Nuclear Medicine, Medical Faculty, UKIM Skopje. In all patients thyroid ultrasound and fine needle aspiration cytology (FNAC) were performed. Surgically were removed 84 nodules and ultrasonography and cytology data were compared to histology results. RESULTS: From all examined ultrasonographic features, significant association with malignancy has been found for hypoechogenecity, marked central vascularisation, ultrasound suspicious nodules (including at least two suspicious features) and marginal for presence of microcalcifications. Highest sensitivity was obtained for hypoechogenecity, and highest specificity for microcalcifications and marked central vascularisation. CONCLUSION: Awareness of the suspicious ultrasound features is mandatory in order to optimize diagnostic and therapeutic approach to the vast number of patients with thyroid nodules. PMID- 27275310 TI - Evaluation of Neonatal Hemolytic Jaundice: Clinical and Laboratory Parameters. AB - BACKGROUND: Neonatal jaundice that occurs in ABO or Rhesus issoimunisation has been recognized as one of the major risk factors for development of severe hyperbilirubinemia and bilirubin neurotoxicity. AIM: Aim of our study was to investigate clinical and laboratory parameters associated with hemolytic jaundice due to Rh and ABO incompatibility and compare results with the group of unspecific jaundice. MATERIAL AND METHODS: One hundred sixty seven (167) neonatal hyperbilirubinemia cases were included in the study, 24.6% of which presented with ABO/Rhesus type hemolytic jaundice, and the rest with unspecific jaundice. Evaluation included: blood count, reticulocites, serum bilirubin, aminotransferases, blood grouping, and Coombs test, also the day of bilirubin peak, duration of the hyperbilirubinemia, and additional bilirubin measurements. RESULTS: We showed significantly lower mean values of hemoglobin, erythrocytes and hematocrit and significantly higher values of reticulocytes in the group of ABO/Rh incompatibility compared to the group of jaundice of unspecific etiology; also an earlier presentation and a higher-grade jaundice in this group. CONCLUSIONS: The laboratory profile in ABO/Rh isoimmunisation cases depicts hemolytic mechanism of jaundice. These cases carry a significant risk for early and severe hyperbilirubinemia and are eligible for neurodevelopmental follow-up. Hematological parameters and blood grouping are simple diagnostic methods that assist the etiological diagnosis of neonatal hyperbilirubinemia. PMID- 27275311 TI - Cardiac Affection in Type 1 Diabetic Patients in Relation to Omentin. AB - AIM: To evaluate cardiac affection in type 1 diabetes in relation to Omentin. PATIENTS AND METHODS: Sixty two diabetics and 30 volunteer of the same age and sex were included as a control group. Blood sample was taken for assessment of omentin and oxidized low density lipoprotein (OxLDL), glycosylated hemoglobin (HbA1) and lipid profile. Urine sample was taken for assessment of albumin/creatinine ratio. 24 hour holter was also done. T-test, simple correlation followed by stepwise multiple regression analysis was used for analysis of data. RESULTS: Parameters of 24 hour holter were significantly lower in diabetics. Omentin was significantly lower, while OxLDL were significantly higher than controls. RMSSD, ST deviation and OxLDL were the parameters related to omentin by stepwise multiple regression analysis in diabetics. CONCLUSION: Diabetic patients had a cardiac autonomic neuropathy. A significant reduction of omentin and elevation OxLDL imply that they influence glucose metabolism in type 1 diabetes. Omentin had a significant relation to 24 hr holter which may reflect its role in cardiac affection. Omentin and OxLDL had a role in renal affection. PMID- 27275313 TI - Parkinsonism as a Complication of Bariatric Surgery. AB - BACKGROUND: The association between Parkinsonism and BS has already been reported in only three patients worldwide. CASE SUMMARY: We report a 39-years old Kuwaiti female who presented with parkinsonian features and mononeuropathy (carpal tunnel syndrome) 3 years after a vertical sleeve gastrectomy operation. CONCLUSION: We conclude that with the increasing popularity of bariatric surgery, clinicians will need to recognize and manage neurologic complications that may appear soon after or years to decades later. Thorough evaluation is essential for any patient who has undergone bariatric surgery and develops neurologic symptoms. PMID- 27275312 TI - Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis. AB - AIM: We are presenting an uncommon case of pulmonary embolism, followed with an acute myocardial infarction, in a patient with progressive systemic sclerosis. CASE PRESENTATION: A female 40 years of age was admitted with signs of pulmonary embolism, confirmed with CT scan, which also reviled a thrombus in the right ventricle. The patient had medical history of systemic sclerosis since the age of 16 years. She suffered an ischemic stroke 6 years ago, but she was not taking any anticoagulant or antithrombotic medications ever since. She received a treatment with thrombolytic therapy, and subsequent UFH, but, on the second day after receiving fibrinolysis, she felt chest pain accompanied with ECG changes consistent for ST-segment elevation myocardial infarction (STEMI). Urgent coronary angiography was undertaken, which reviled cloths causing total occlusion in 4 blood vessels, followed with thromboaspiration, but without successful reperfusion. Several hours later the patient developed rapid deterioration with letal ending. During the very short hospital course, blood sampling reviled presence of antiphospholipid antibodies. CONCLUSION: The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis. PMID- 27275314 TI - Pheochromocytoma and Neurofibromatosis Type 1 in a Patient with Hypertension. AB - BACKGROUND: Neurofibromatosis type 1 is an autosomal dominant condition that has a variety of clinical manifestations. Essential or secondary hypertension may be associated with neurofibromatosis. A rare finding is hypertension due to pheochromocytoma in patient with neurofibromatosis type 1. CASE REPORT: We present a case with a 7-year medical history of hypertension which was poorly controlled and with wide variations of blood pressure before the examination. Investigations did not reveal a secondary cause of hypertension. After the physical examination and establishing the diagnosis of neurofibromatosis, as well as the history of symptomes suggestive of catecholamine discharge, diagnostic procedures for pheochromocytoma were undertaken. Abdominal CT and MRI have proven the presence of a right adrenal tumor mass which was suspected to be a pheochromocytoma. Patient was preoperatively treated for two weeks with alpha and beta blokers and right adrenalectomy was performed. Perioperatively and on a longer term, blood pressure remained well controlled with less antihypertensive therapy. Diagnosis and management of pheochromocytoma in neurofibromatosis involves a dermatologist, endocrinologist, nephrologist and an urologist and requires a well-coordinated multidisciplinary approach. CONCLUSIONS: Pheochromocytoma, although a rare condition in patients with neurofibromatosis, may be a cause for uncontrolled hypertension, as well as other cardiovascular complications and the clinician should do all available clinical investigations to confirm it or exclude it on time. PMID- 27275315 TI - Clinical Assessment of the Efficiency of Low Level Laser Therapy in the Treatment of Oral Lichen Planus. AB - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa of uncertain etiology. AIM: To evaluate the effect of using low level laser therapy (LLLT (970 nm Siro laser Advance) for the treatment of symptomatic (OLP). SUBJECTS AND METHODS: The present study was conducted on ten patients suffering from persistent oral lichen planus (OLP). Patients were treated with diode laser (970nm) for the symptomatic relief of pain and burning sensation. The patients were assessed before, during and after the completion of the laser treatment which was done twice weekly for two successive months with maximum of ten sessions. The assessment was performed using visual analogue scale (VAS) and clinical investigation for each patient. RESULTS: Detailed significant reduction in lesion size and showed complete remission of burning sensation and pain. No reported complications or therapy side effects were observed in any of the treated patients. CONCLUSION: Diode laser therapy seems to be an effective adjunctive treatment modality for relieving pain and clinical symptoms of OLP. PMID- 27275316 TI - Impact of Platelet-Rich Plasma on Bone Height Changes around Platform Switched Implants Supporting Mandibular Overdentures in Controlled Diabetic Patients. AB - BACKGROUND: The platform switching concept was recently introduced to implant dentistry involving the reduction of restoration abutment diameter with respect to the diameter of dental implant. Long-term follow-up around these implants showed higher levels of bone preservation and proper stress distribution and improved esthetics. AIM: The aim of the present study was to evaluate the changes in bone height by means of radiographic examination around platform switched implant supporting mandibular overdentures in controlled diabetic patients. SUBJECTS AND METHODS: Fourteen male complete edentulous patients were selected and enrolled in a follow-up study plan. Split mouth technique was applied; one side implant chosen randomly with Platelet-rich-plasma (PRP) and the other without PRP, bone height changes was assessed by Cone Beam Computed Tomography (CBCT) radiographic examination after 3 months, 6 months, 9 months and 1 year later. RESULTS: There was increase in bone height loss in both sides but with no statistical significance difference between the two sides after 3 months, 6 months, 9 months and 1 year respectively. CONCLUSION: The result of this article satisfied the patients both esthetically and functionally with recorded increase in bone height loss. PMID- 27275317 TI - Resilience and Quality of Life in Breast Cancer Patients. AB - BACKGROUND: Many studies have shown that a relationship exists between quality of life (QoL) and resilience in breast cancer patients, but few studies present information on the nature of this relationship of resilience on QoL. Our aim was to examine the relationship between resilience and quality of life in breast cancer patients. METHODS: QoL was measured in 218 consequent breast cancer patients, with EORTC - QLQ Core 30 questionnaire, and EORTC QLQ-BR23. The resilience was measured with Connor Davidson Resilience Scale. RESULTS: The global quality of life was positively correlated with the levels of resilience (R = 0.39 p < 0.001). All functional scales (physical, role, emotional, cognitive and social functioning was in a positive correlation with resilience. The symptoms severity (fatigue, nausea and vomitus, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) was in negative correlation with resilience. Less resilient breast cancer patients reported worse body image and future perspective and suffered from more severe adverse effects of systemic therapy, and arm/breast symptoms. CONCLUSION: Our findings show that psychological resilience affects different aspects of health-related quality of life. More resilient patients have significantly better quality of life in almost all aspects of QoL. PMID- 27275318 TI - Hepatocellular Carcinoma: Risk Factors, Diagnosis and Treatment. AB - Hepatocellular carcinoma (HCC) is the most often primary cancer of the liver and is one if the leading cause of cancer-related death worldwide. The incidence of HCC has geographic distribution with the highest levels in countries with developing economies. Patients with hepatocellular carcinoma have poor prognosis despite the achievements in surgery techniques and other therapeutic procedures and it is a reason why continuous attention should be paid to this issue. This article provides an overview of this disease based on an extensive review of relevant literature. The article summarizes the current risk factors, diagnosis, staging and the management of HCC. PMID- 27275319 TI - How to Verify Plagiarism of the Paper Written in Macedonian and Translated in Foreign Language? AB - AIM: The aim of this study was to show how to verify plagiarism of the paper written in Macedonian and translated in foreign language. MATERIAL AND METHODS: Original article "Ethics in Medical Research Involving Human Subjects", written in Macedonian, was submitted as an assay-2 for the subject Ethics and published by Ilina Stefanovska, PhD candidate from the Iustinianus Primus Faculty of Law, Ss Cyril and Methodius University of Skopje (UKIM), Skopje, Republic of Macedonia in Fabruary, 2013. Suspected article for plagiarism was published by Prof. Dr. Gordana Panova from the Faculty of Medical Sciences, University Goce Delchev, Shtip, Republic of Macedonia in English with the identical title and identical content in International scientific on-line journal "SCIENCE & TECHNOLOGIES", Publisher "Union of Scientists - Stara Zagora". RESULTS: Original document (written in Macedonian) was translated with Google Translator; suspected article (published in English pdf file) was converted into Word document, and compared both documents with several programs for plagiarism detection. It was found that both documents are identical in 71%, 78% and 82%, respectively, depending on the computer program used for plagiarism detection. It was obvious that original paper was entirely plagiarised by Prof. Dr. Gordana Panova, including six references from the original paper. CONCLUSION: Plagiarism of the original papers written in Macedonian and translated in other languages can be verified after computerised translation in other languages. Later on, original and translated documents can be compared with available software for plagiarism detection. PMID- 27275320 TI - The Study of Cellular and Molecular Physiological Characteristics of Sperm in Men Living in the Aral Sea Region. AB - BACKGROUND: Extreme environmental situation in the Aral crisis has caused a massive chemical pollution of the territory for decades with high doses of pesticides, herbicides. Discharge of industrial waste into the rivers that feed the Aral Sea has lead to the development of various pathological processes in the human body, as well as disruption of reproductive function in young men. AIM: To evaluate the performance of molecular cellular changes in the sperm of men under the influence of dust and salt aerosols in Aral Sea region. MATERIAL AND METHODS: Clinical and laboratory studies were conducted in men 5 settlements (Aralsk-city, v. Aiteke-Bi, v. Zhalagash, v. Zhusaly, v. Shieli). We have studied male ejaculate obtained after 4-5 days of abstinence, and placed it in a warm tube with a glass stopper. On the investigation proceeded ejaculate within 20-30 minutes after its preparation, during which time he was subjected to liquefaction. Isolation and quantification of ASF, RNA, DNA, and determining the fraction of histones in sperm was performed by the method of Markusheva and Savina. RESULTS: It was found that the value of ASF in the semen of men living in the zone of ecological disaster higher compared with the values of parameters in men living in the area of environmental crisis, and this trend is observed in all age groups. The study of circulating extracellular DNA and RNA in the sperm of men registered their decline with a corresponding increase of acid precursors that can be attributed to the degradation of nucleic acids under the influence of negative factors in the complex area of ecological trouble. Also, according to a study in men residing in the areas of environmental catastrophe at the age of 18 29 years, found an increased content of the H1 histone H2A lower total fraction, H3, H4 - and a sharp increase in histone H2B content - histones. CONCLUSIONS: Men living in environmentally disadvantaged areas of Kyzylorda region under the influence of dust and salt aerosols and other toxicants leads to disruption of the reproductive function in men. PMID- 27275321 TI - Expression of OCT-4 and SOX-2 in Bone Marrow-Derived Human Mesenchymal Stem Cells during Osteogenic Differentiation. AB - AIM: Determine the levels of expression of pluripotency genes OCT-4 and SOX-2 before and after osteogenic differentiation of human mesenchymal stem cells (hMSCs). METHODS: Human MSCs were derived from the bone marrow and differentiated into osteoblasts. The analyses were performed on days 0 and 14 of the cell culture. In vitro differentiation was evaluated due to bone markers - alkaline phosphatase (AP) activity and the messenger RNA (mRNA) expression of AP and bone sialoprotein (BSP). The OCT-4 and SOX-2 expression was evaluated at mRNA level by real-time qPCR and at protein level by immunocytochemistry. RESULTS: In vitro cultures on day 14 showed an increase in AP activity and upregulation of AP and BSP gene expression. OCT-4 and SOX-2 in undifferentiated hMSCs on day 0 is detectable and very low compared to tumor cell lines as a positive control. Immunocytochemistry detected OCT-4 in the cell nuclei prior (day 0) and post differentiation (day 14). On the same time points, cultures were negative for SOX 2 protein. CONCLUSION: Messenger RNA for pluripotency markers OCT-4 and SOX-2 isolated from hMSCs was less present, while OCT-4 protein was detected in cell nuclei prior and post differentiation into osteoblast lineage. PMID- 27275322 TI - Role of Cardiac Myocytes Heart Fatty Acid Binding Protein Depletion (H-FABP) in Early Myocardial Infarction in Human Heart (Autopsy Study). AB - BACKGROUND: Many immunohistochemical markers have been used in the postmortem detection of early myocardial infarction. AIM: In the present study we examined the role of Heart-type fatty acid binding protein (H-FABP), in the detection of early myocardial infarction. MATERIAL AND METHODS: We obtained samples from 40 human autopsy hearts with/without histopathological signs of ischemia. RESULTS: All cases of definite and probable myocardial infarction showed a well-defined area of H-FABP depletion. All of the control cases showed strong H-FABP expression, except two markedly autolysed myocardial samples that showed affected antigenicity. CONCLUSION: Thus, we suggest H-FABP as being one of the valuable tools facing the problem of postmortem detection of early myocardial infarction/ischemia, but not in autolysis. PMID- 27275323 TI - Susceptibility of Urinary Tract Bacteria to Newer Antimicrobial Drugs. AB - Urinary tract infections (UTIs) are among the commonest types of bacterial infections. The antibiotic treatment for UTIs is associated with important medical and economic implications. Many different microorganisms can cause UTIs though the most common pathogens are E. coli and members of family Enterobacteriaceae. The knowledge of etiology and antibiotic resistance pattern of the organisms causing urinary tract infection is essential. The present study was undertaken to evaluate trends of antibiotic susceptibility of commonly isolated uropathogens using newer antimicrobial agents, prulifloxacin, fosfomycin (FOM) and doripenem. We conclude that maintaining a record of culture results and the antibiogram may help clinicians to determine the empirical and/or specific treatment based on the antibiogram of the isolate for better therapeutic outcome. PMID- 27275324 TI - The Validity of Body Adiposity Indices in Predicting Metabolic Syndrome and Its Components among Egyptian Women. AB - AIM: To assess the associations between the body adiposity indices and risk of metabolic syndrome (MS) and its components in Egyptian women and to evaluate their predictive power. MATERIALS AND METHODS: This was a cross-sectional analysis performed on 180 Egyptian women aged between 25-35 years. They were 90 women with MS diagnosed by International Diabetes Federation (IDF) and 90 healthy age matched controls. Body adiposity index (BAI), body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were calculated and serum samples were analyzed for metabolic parameters. Receiver operating characteristic curves (ROC) was used to determine the discriminatory capacity of BAI, WHR WHtR and BMI for MS. RESULTS: Area under the curve (AUC) was highest for BIA, followed by WHR, WHtR and then BMI. All adiposity indices were significantly correlated with metabolic components and BAI had the highest correlation coefficients compared to other indices. CONCLUSION: BAI is a practical predictor for MS and has satisfactory diagnostic accuracy for diagnosing MS among Egyptian women and can be used in addition to WHR, WHtR and BMI for identifying MS in the field studies. PMID- 27275326 TI - Fractional Carbon Dioxide Laser in Treatment of Acne Scars. AB - BACKGROUND: Scars appear as a result of skin damage during the process of the skin healing. There are two types of acne scars, depending on whether there is a loss or accumulation of collagen: atrophic and hypertrophic. In 80-90% it comes to scars with loss of collagen compared to smaller number of hypertrophic scars and keloids. AIM: The aim of the study was to determine efficiency and safety of fractional carbon dioxide laser in the treatment of acne scars. MATERIAL AND METHODS: The study was carried out in Acibadem Sistina Clinical Hospital, Skopje at the Department of Dermatovenerology, with a total of 40 patients treated with fractional carbon dioxide laser (Lutronic eCO2). The study included patients with residual acne scars of a different type. RESULTS: Comedogenic and papular acne in our material were proportionately presented in 50% of cases, while the other half were the more severe clinical forms of acne - pustular inflammatory acne and nodulocystic acne that leave residual lesions in the form of second, third and fourth grade of scars. CONCLUSION: The experiences of our work confirm the world experiences that the best result with this method is achieved in dotted ice pick or V-shaped acne scars. PMID- 27275325 TI - Relation between microRNAs and Apoptosis in Hepatocellular Carcinoma. AB - AIM: To determine the relation between serum microRNAs and apoptotic markers as regards development of HCC to understand the underlying mechanism of HCV related hepatocarcinogenesis. PATIENTS AND METHODS: A total of 65 serum samples (25 samples from controls, 20 samples from hepatitis and 20 samples from HCC patients) were collected for miRNAs (mir 21, mir 199-a, and mir 155) detection. Human Programmed cell death protein-4 (PDCD-4) and Human Cytochrome-C (CYT-C) were determined. RESULTS: miRNAs 21 and 155 were over expressed in sera of patients with HCC compared to patients with chronic hepatitis (p < 0.0001). While serum means values of miR 199a was significantly decreased among HCC group patients when compared to patients with chronic hepatitis (p < 0.0001). The serum levels of PCDC4 and CYTC were increased in patients with HCC when compared to chronic hepatitis patients. They were also increased in patients with chronic hepatitis when compared to controls (p < 0.05, significant). There was direct correlations between apoptotic markers and oncomirs miRNAs 21 and 155 while apoptotic markers were inversely correlated with miRNA 199-a. CONCLUSION: Both microRNAs and apoptotic markers have roles in HCC pathogenesis. It seems that oncogenic microRNAs induce liver carcinogenesis in HCV patients irrespective of suppression of apoptosis. PMID- 27275327 TI - Association between Nephrolithiasis, Hypertension and Obesity in Polycystic Kidney Disease. AB - AIM: We aim to define the correlations between nephrolithiasis, hypertension, age and obesity in patients with autosomal dominant polycystic kidney disease (ADPKD) in Albania. MATERIAL AND METHODS: We included 100 patients with autosomal dominant polycystic kidney from 2011 to 2014. The patients underwent X-ray and renal ultrasonography. We performed the metabolic evaluation of blood and urine. RESULTS: The patients with renal stones had a higher level of mean systolic and diastolic blood pressure compared with patients without stones (155 +/- 12 mmHg vs. 145 +/- 8 mmHg, and 105 +/- 0.9 mmHg vs. 92 +/- 1.28 mmHg, respectively). Patients with renal stones were older (47 +/- 15 vs. 38 +/- 5 years), had a higher prevalence of obesity [body mass index (BMI): 28 +/- 2.4 vs. 25.7 +/- 0.6], had higher levels of total cholesterol level (220 +/- 5 mg/dl vs. 203 +/- 4 mg/dl) as well as triglyceride levels (160 +/- 9 mg/dl vs. 126 +/- 4 mg/dl), compared with no renal stone individuals. CONCLUSION: ADPKD patients with renal stones in our study had a higher mean level of systolic and diastolic blood pressure, BMI and cholesterol and triglycerides levels compared with individuals without renal stones. PMID- 27275328 TI - Prosthetic Subclavian-Aortic Bypass as a Safe Surgical Technique for the Coarctation of the Aorta in Adults. AB - BACKGROUND: Coarctation represents 5-8% of congenital heart disease. Residual hypertension remains the main problem after late correction. Surgical treatment in the adult remains a challenge for the surgeon. Our prefered method used in this category is the Subclavian-aortic bypass. MATERIAL AND METHODS: We have reviewed our registry for the period of 12 years (1998- 2010) and we found a group of 18 adult patients being operated for coarctation of the aorta. The mean age of this group of patients was 24.7 +/- 8.43 years (range 16-42 years). 13 were males and 5 females. RESULTS: Sugical technique: Most of the patients (13 pts, 72%) which were obviously treated with subclavian-aortic bypass with a Dacron prostheses. Mean preoperative and postoperative pressure gradients measured by echocardiography were 77.7 +/- 20.16 mmHg and 22.3 +/- 9.14 mmHg respectively. No mortality was observed in this series of patients. Chylothorax was the only complication observed in one patient in the early postoperative period. CONCLUSION: Coarctation of the aorta in adults is treated with optimal early results at our surgical centre. Subclavian-aortic bypass grafting requires less aortic dissection, can be performed with a partially occluding clamp, and does not compromise the spinal cord vascularization. PMID- 27275329 TI - Analysis of Lymphocyte Immunological Reactivity in Patients with Pleural Effusions of Different Aetiology. AB - BACKGROUND: The proportion of T and B lymphocytes in pleural fluids and blood may point to the presence of local immunological phenomena in pleural disorders. AIM: Aim of study was to evaluate the lymphocyte phenotype and the ratio between helper (CD4+) and cytotoxic/suppressor (CD8+) lymphocytes in malignant and non malignant effusions. MATERIAL AND METHODS: We studied 48 patients with pleural effusions. First group had 18 patients with tuberculosis pleural effusions; second group had 20 patients with malignant pleural fluids, third group had 10 patients with transudates and 30 healthy controls. We investigated the distribution of T and B lymphocytes, T cells with helper/inducer CD4 or suppresser/cytotoxic CD8 phenotypes and the CD16 subset. RESULTS: Results showed decreases levels of CD3, CD4, and CD16 T cells in blood of patients versus healthy controls. There were increases in the percentage of the CD3 and CD4 T cells in the pleural fluid compared with values in the blood with statistical significance in tuberculous pleurisy. The values of CD8 were similar in the pleural fluid and in blood. Levels of CD16 were non-significantly higher in pleural fluid in all groups. CONCLUSION: This study confirms the hypothesis that pleural cavity is compartment with immunological reactivity and results could be used in differential diagnosis together with other examinations. PMID- 27275330 TI - Maternal and Neonatal Effects of Vasopressors Used for Treating Hypotension after Spinal Anesthesia for Caesarean Section: A Randomized Controlled Study. AB - AIM: The aim of the study was to examine whether ephedrine and phenylephrine were different in their efficacy for managing maternal hypotension and their effect of adverse maternal and neonatal outcome. METHODS: A double-blind randomized controlled study in healthy pregnant women ASA physical status 2, which underwent elective caesarian delivery under spinal anesthesia. Patients were randomized to receive an intravenous bolus of either phenylephrine (Ph group) or ephedrine (E group) immediately after the episode of hypotension after spinal anesthesia. Maternal and neonatal outcomes were recorded. RESULTS: Two hundred and two (202) pregnant women at term were entered in this study. There were no differences between group E and group Ph regarding the incidence of hypotension after vasopressor therapy, and the incidence of nausea and vomiting. There was no significant difference between groups in the first-minute and the 5th minute Apgar score, none of the neonates had the true fetal acidosis. CONCLUSIONS: Ephedrine and phenylephrine have the same efficacy in treating hypotension after spinal anesthesia for caesarean section. The use of Phenylephrine was associated with better fetal acid-base status, and there were no differences on Apgar score values and on the incidence of maternal bradycardia and hypotension. PMID- 27275332 TI - Validation of the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4) Among Patients with Schizophrenia. AB - BACKGROUND: The main goal of psychiatric care is not to be focused only on reducing psychopathological symptoms, but on improvement of the patient's quality of life. AIM: To examine validation and reliability SQLS-R4 among patients with schizophrenia. METHODS: The sample consisted of 61 outpatients with schizophrenia attending the Psychiatry Hospital "Skopje". nclusion criteria for subject selection were: 1) age more than 18 years, 2) clinically stable (not acutely ill or has not been recently hospitalized at least for the past 3 months). They completed SQLS-R4 and SF36 questioners. RESULTS: The internal consistency reliability was satisfactory for both the psychosocial and vitality domains (Cronbach's alpha = 0.928, 0.83). Most of the items were significantly correlated with own scale score (from 0.189 to 0.687). The average of the score for the psychosocial quality life was 39.9 +/- 8.6 (sometimes), for the cognition and vitality was 26.5 +/- 6.1 (sometimes) (SQLS-R4). There was moderate correlation between SF 36-energy with SQOLS - motivation and energy; SF 36-mental health correlation with SQOLS-psychosocial. CONCLUSION: SQLS-R4 appears to offer excellent potential as an easily administered and patient acceptable assessment and monitoring measure of quality of life (QoL). However, a principle psychometric criterion crucial to the use and validity of the instrument concerns the underlying factor structure. PMID- 27275331 TI - Cardiac Biomarkers and Left Ventricular Hypertrophy in Asymptomatic Hemodialysis Patients. AB - BACKGROUND: Cardiac biomarkers are often elevated in dialysis patients showing the presence of left ventricular dysfunction. The aim of the study is to establish the plasma levels of high-sensitivity cardiac troponin T (hs TnT), precursor of B-natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hs CRP) and their relation to the presence of left ventricular hypertrophy (LVH) in patients undergoing hemodialysis without signs of acute coronary syndrome or heart failure. MATERIAL AND METHODS: We studied 48 patients 26 men and 22 women. Pre and postdialysis levels of hs cTnT, NT-proBNP and hs CRP were measured at week interim procedure. Patients were divided in two groups according to the presence of echocardiographic evidence of LVH - gr A - 40 patients (with LVH), and gr B - 8 patients (without LVH). RESULTS: In the whole group of patients was found elevated predialysis levels of all three biomarkers with significant increase (p < 0.05) after dialysis with low-flux dialyzers. Predialysis values of NT-proBNP show moderate positive correlation with hs cTnT (r = 0.47) and weaker with hs CRP (r = 0.163). Such dependence is observed in postdialysis values of these biomarkers. There is a strong positive correlation between the pre and postdialysis levels: for hs cTnT (r = 0.966), for NT-proBNP (r = 0.918) and for hs CRP (r = 0.859). It was found a significant difference in the mean values of hs cTnT in gr. A and gr. B (0.07 +/- 0.01 versus 0.03 +/- 0.01 ng/mL, p < 0.05) and NT-proBNP (15,605.8 +/- 2,072.5 versus 2,745.5 +/- 533.55 pg/mL, p < 0.05). Not find a significant difference in hs CRP in both groups. CONCLUSIONS: The results indicate the relationship of the studied cardiac biomarkers with LVH in asymptomatic patients undergoing hemodialysis treatment. PMID- 27275333 TI - Thumb Reconstruction Using Foucher's Flap. AB - BACKGROUND: Extensive pulp defects of the thumb, with the exposure of tendon or bone, are challenging reconstructive problems. Surgical treatment includes the use of local, regional, and free flaps. AIM: This paper is focused in Foucher's neuro vascular flap. First DMCA or Foucher's pedicle flap is a successful thumb reconstruction method, especially in patients not disturbed by its cosmetic appearance. MATERIAL AND METHODS: The first dorsal metacarpal artery (FDMCA) arises from the radial artery in the first intermetacarpal space, just distal to the tendon of the extensor pollicis longus. Pulp area of the thumb is the area where Foucher's flap is more utilizable. This technique has other applications such as first web reconstruction, thumb lengthening, and following resection of tumors on the dorsum of the hand. RESULTS: We have in study 7 cases with work related trauma in two years period of time, between 2012 and 2014. We had only one partial flap survival and all the other flaps survived entirely. We have also taken in consideration subjective satisfaction with a range score from 4 to 10, cold intolerance, flap area and donor site sensibility with a range score from low to medium to normal. CONCLUSION: Careful pedicle discovery, secured elevation, pedicle strangulation prevention are very important for flap survival. PMID- 27275334 TI - Echocardiography as a Predicting Method in Diagnosis, Evaluation and Assessment of Children with Subvalvar Aortic Stenosis. AB - BACKGROUND: Obstruction to the left ventricular outflow of the heart may be above the aortic valve (5%), at the valve (74%), or in the subvalvar region (23%). These anomalies represent 3 to 6% of all patients with congenital heart defects (CHD), and it occurs more often in males (male-female ratio of 4:1). AIM: The purpose of this study was to determine the sensitivity and specificity of transthoracic echocardiography in diagnosis of discrete subaortic membrane, to determine convenient time for surgical intervention, and for identifying involvement of the aortic valve by subaortic shelf. MATERIAL AND METHODS: A retrospective review of the medical records and echocardiograms of 18 patients [14 male (77%) and 4 female (23%)] with discrete subaortic membrane, aged 11 month to 12 years, with mean age of 5 years and 3 month, diagnosed at the Pediatric Clinic in Prishtina, during the period September, 1999 and December, 2010 were done. RESULTS: Four patients, in neonatal age were operated from critical coarctation of the aorta and, initial signs of congestive heart failure were presented. 2 of them were operated in Belgrade, Serbia and 2 in Lausanne, Switzerland. CONCLUSION: In all presented patients bicuspid aortic valve was noted, but none of them subaortic membrane was registered. PMID- 27275335 TI - Prevalence of Diabetes Mellitus in Patients with Chronic Kidney Disease. AB - BACKGROUND: Chronic kidney disease (CKD) became a new epidemic of the twentieth and twenty-first centuries. Diabetic nephropathy is one of the leading causes of end-stage renal failure as a result of the diabetes epidemic worldwide. AIM: The aim of our study was to assess the prevalence of CKD in the Republic of Macedonia and its association with diabetes mellitus. MATERIALS AND METHODS: The study was a part of a study conducted in 2006 in terms of screening for early detection of kidney disease. It was a cross-sectional study based on a random sample of patients aged > 20, consecutively consulting their primary physician for any cause. Fifty physicians throughout the country were included in the study. A total of 2637 patients have been analyzed based on integrity data. GFR was estimated using corrected values of serum creatinine and calculating kidney function by the Cockroft & Gault formula, adjusted for body surface using the Gehan & George formula. Patients with estimated glomerular filtration rate (eGFR) less than 60 ml/min were considered as having CKD. Blood pressure, body weight, height, serum creatinine, glucose, hemoglobin, hematocrit, urinalysis and medical history for presence of cardiovascular diseases or diabetes were also assessed. RESULTS: The mean age of the subjects was 45.97 +/- 16.55 SD and 17.97% were older than 60. Regarding gender, 44.14% were males. The prevalence of diabetes mellitus was 13.9%. Subjects with CKD (eGFR less than 60 ml/min) were 7.53% of the total. Subjects aged 60 or above, had 20 times higher risk of having CKD (eGFR less than 60 ml/min/1.73 m(2)). Out of the total group of subjects, 13.9% had diabetes mellitus and they had 3.13 times higher risk of having CKD stage 3-5 (eGFR less than 60 ml/min/1.73 m(2)) when compared to non-diabetics. The results showed that diabetes was significantly more associated with lower eGFR (less than 60 ml/min/1.73 m(2)) in younger subjects (age less than 60) compared to older ones (odds ratio 3.29 versus 1.21). CONCLUSION: Our study showed that chronic kidney disease is frequent in the Republic of Macedonia and is associated with older age and diabetes. Diabetes had a significantly stronger association with CKD at younger age. PMID- 27275336 TI - Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women. AB - BACKGROUND: Insulin resistance (IR) is closely associated with diabetes mellitus. On the other hand, increased visceral fat in menopause is also associated with IR, which makes postmenopausal diabetic women in a big risk for cardiovascular diseases. There are conflicting reports about the effects on hormone replacement therapy (HRT) on IR. AIM: The aim of the study was to investigate the effects of HRT on IR. METHODS: A total of 40 postmenopausal women with type 2 diabetes were enrolled and followed for 12 months. Half of them were assigned to take HRT, while the other half made the control group. Fasting plasma glucose (FPG) and insulinemia were measured in both groups at baseline and after 12 months. IR was represented by Homeostatic model assessment for IR (HOMA-IR). RESULTS: HRT was associated with significant decrease in HOMA-IR, FPG and insulinemia in the examined group. There was no significant reduction in FPG and no significant increase in insulinemia levels and HOMA-IR values in control group after 12 months. CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause. PMID- 27275337 TI - Evaluation of Anesthesia Profile in Pediatric Patients after Inguinal Hernia Repair with Caudal Block or Local Wound Infiltration. AB - AIM: The aim of this study is to evaluate anesthesia and recovery profile in pediatric patients after inguinal hernia repair with caudal block or local wound infiltration. MATERIAL AND METHODS: In this prospective interventional clinical study, the anesthesia and recovery profile was assessed in sixty pediatric patients undergoing inguinal hernia repair. Enrolled children were randomly assigned to either Group Caudal or Group Local infiltration. For caudal blocks, Caudal Group received 1 ml/kg of 0.25% bupivacaine; Local Infiltration Group received 0.2 ml/kg 0.25% bupivacaine. Investigator who was blinded to group allocation provided postoperative care and assessments. Postoperative pain was assessed. Motor functions and sedation were assessed as well. RESULTS: The two groups did not differ in terms of patient characteristic data and surgical profiles and there weren't any hemodynamic changes between groups. Regarding the difference between groups for analgesic requirement there were two major points - on one hand it was statistically significant p < 0.05 whereas on the other hand time to first analgesic administration was not statistically significant p = 0.40. There were significant differences in the incidence of adverse effects in caudal and local group including: vomiting, delirium and urinary retention. CONCLUSIONS: Between children undergoing inguinal hernia repair, local wound infiltration insures safety and satisfactory analgesia for surgery. Compared to caudal block it is not overwhelming. Caudal block provides longer analgesia, however complications are rather common. PMID- 27275338 TI - The Impact of Treatment with Beta-Blockers upon Mortality in Chronic Heart Failure Patients. AB - BACKGROUND: Besides the conventional therapy for heart failure, the diuretics, cardiac glycosides and ACE-inhibitors, current pharmacotherapy includes beta blockers, mainly because of their pathophysiological mechanisms upon heart remodeling. AIM: The study objective was to assess the cardiovascular mortality in the beta-blocker therapy group and to correlate it with the mortality in the control group as well as to correlate the combined outcome of death and/or hospitalization for cardiovascular reason between the two groups. MATERIALS AND METHODS: The study included 113 chronic heart failure patients followed up for a period of 18 months. The therapy group received conventional therapy plus the target dose of beta blockers, and the control group received the conventional therapy only. The therapy group was divided in three separate subgroups in terms of the type of beta-blocker (Metoprolol subgroup, Bisoprolol and Carvedilol subgroup). To compare the mortality and the combined outcome, the RRR (relative risk reduction) and NNT (number needed to treat) were used, as well as the survival analysis by Kaplan-Meier. RESULTS: The results showed the following: in regards of the cardiovascular mortality, the relative risk for death in the therapy group was 34%, which, though statistically not significant, is of great clinical significance. In regards of the combined outcome (death and/or number of hospitalizations) the results showed a RRR of 40% in the therapy group compared to the control group, which is statistically highly significant. CONCLUSION: The study confirmed that patients with stable chronic heart failure, treated with optimal doses of beta-blockers, show a significant reduction of the risk from death as well as combined outcome (death and/or number of hospitalizations). PMID- 27275339 TI - Refractory Epilepsy-MRI, EEG and CT scan, a Correlative Clinical Study. AB - OBJECTIVES: Refractory epilepsies (RE), as well as, the surgically correctable syndromes, are of great interest, since they affect the very young population of children and adolescents. The early diagnosis and treatment are very important in preventing the psychosocial disability. Therefore MRI and EEG are highly sensitive methods in the diagnosis and localization of epileptogenic focus, but also in pre-surgical evaluation of these patients. The aim of our study is to correlate the imaging findings of EEG, MRI and CT scan in refractory symptomatic epilepsies, and to determine their specificity in detecting the epileptogenic focus. METHODS: The study was prospective with duration of over two years, open labelled, and involved a group of 37 patients that had been evaluated and diagnosed as refractory epilepsy patients. In the evaluation the type and frequency of seizures were considered, together with the etiologic factors and their association, and finally the risk for developing refractory epilepsy was weighted. EEG and MRI findings and CT scan results were evaluated for their specificity and sensitivity in detecting the epileptogenic focus, and the correlation between them was analyzed. RESULTS: Regarding the type of seizures considered in our study, the patients with PCS (partial complex seizures) dominated, as opposed to those with generalized seizures (GS) (D=1.178, p < 0.05). Positive MRI findings were registered in 28 patients (75.7%). Most of them were patients with hippocampal sclerosis, 12 (42.8%), and also they were found to have the highest risk of developing refractory epilepsy (RE) (Odds ratio = 5.7), and the highest association between the etiologic factor and refractory epilepsy (p < 0.01). In detecting the epileptogenic focus, a significant difference was found (p < 0.01) between MRI and CT scan findings, especially in patients with hippocampal sclerosis and cerebral malformations. There was a strong correlation between the MRI findings and the etiologic factor (R = 1), and for CT scan and etiologic factor an R=0.75 correlation. There was a significant difference between imaging methods MRI/CT (p < 0.1), and CT/EEG (p < 0.05) in detecting the etiologic factor, and little difference was noticed between findings of EEG/MRI. CONCLUSION: Our study confirms that for an accurate diagnosis of refractory epilepsy in patients, a combination of neuroimaging and neurophysiologic methods is required. MRI showed to be highly sensitive in detecting the etiologic factor in RE patients, whereas EEG was sensitive in localization of the epileptogenic focus, with high correlation between these two methods. An early diagnosis of these patients is very important in having a better therapeutic response and prognosis for them. PMID- 27275340 TI - Evaluation of Maternal Complications in Severe Preeclampsia in a University Hospital in Tirana. AB - BACKGROUND: Preeclampsia is a hypertensive multisystem disorder of pregnancy that complicates up to 10% of pregnancies worldwide and is one of the leading causes of maternal and perinatal morbidity and mortality. AIM: To evaluate maternal complications associated with severe preeclampsia. METHODS: This is a retrospective cross-sectional study conducted in the UHOG "Koco Gliozheni", in Tirana. Primary outcomes evaluated: maternal death, eclampsia, stroke, HELLP syndrome, and pulmonary edema. SECONDARY OUTCOMES: renal failure, admission in ICU, caesarean section, placental abruption, and postpartum hemorrhage. Fisher's exact test and Chi-squared test were used as statistical methods. RESULTS: In women with severe preeclampsia we found higher rates of complications comparing to the group with preeclampsia. Eclampsia (1.5% vs. 7.1%, P < 0.001), HELLP syndrome (2.4% vs. 11.0%; P < 0.001), stroke (0.5% vs 1.9%, P = 0.105) pulmonary edema (0.25% vs. 1.3%, P = 0.0035), renal failure (0.9% vs. 2.6%, P = 0.107), admission in ICU (19.5% vs. 71.4%, P = 0.007), caesarean section rates (55.5% vs. 77%, P = 0.508), placental abruption (4.3% vs. 7.8%, P = 0.103) and severe postpartum hemorrhage (3.2% vs. 3.9%, P = 0.628). CONCLUSION: Severe preeclampsia is associated with high rates of maternal severe morbidity and early diagnosis and timely intervention can prevent life treating complications. PMID- 27275341 TI - Splenectomy in Patients with Sickle Cell Disease in Tabuk. AB - BACKGROUND: Sickle cell disease is a common genetic disease in Saudi Arabia; it is an autosomal recessive disorder characterized by production of abnormal hemoglobin S and is associated with high morbidity and mortality. Acute splenic sequestration is a life-threatening complication for this disease. Prophylactic splenectomy is the only effective strategy for preventing future life-threatening episodes. AIM: The aim of this study was to study hospital records for all children aged 2 to 12 year old with Sickle cell disease who underwent splenectomy in Tabuk in Saudi Arabia. METHODS: Records of 24 children (13 males, 11 females) who underwent splenectomy in surgery department of King Salman North West Armed Hospital, Tabuk, Saudi Arabia between 2008 and 2015 were reviewed retrospectively and analyzed for age, sex, indications for splenectomy, surgical technique, preoperative and postoperative length of stay, operative and postoperative complications, acute chest syndrome, painful crises, blood transfusion and fever (preoperative and postoperative). RESULTS: We stressed on the information about the details of operation, the frequency of blood transfusion, fever, acute chest syndrome and painful crisis before and after operation. CONCLUSION: Here we found that blood transfusion frequency decreased after splenectomy. PMID- 27275342 TI - Report on von Willebrand Disease in Malaysia. AB - BACKGROUND: Von Willebrand disease (vWD) is an inherited hemostatic disorder that affects the hemostasis pathway. The worldwide prevalence of vWD is estimated to be 1% of the general population but only 0.002% in Malaysia. AIM: Our present paper has been written to disclose the statistical counts on the number of vWD cases reported from 2011 to 2013. MATERIAL AND METHODS: This article is based on sociodemographic data, diagnoses and laboratory findings of vWD in Malaysia. A total of 92 patients were reported to have vWD in Malaysia from 2011 to 2013. RESULTS: Sociodemographic-analysis revealed that 60% were females, 63% were of the Malay ethnicity, 41.3% were in the 19-44 year old age group and 15.2% were from Sabah, with the East region having the highest registered number of vWD cases. In Malaysia, most patients are predominately affected by vWD type 1 (77.2%). Factor 8, von Willebrand factor: Antigen and vWF: Collagen-Binding was the strongest determinants in the laboratory profiles of vWD. CONCLUSION: This report has been done with great interest to provide an immense contribution from Malaysia, by revealing the statistical counts on vWD from 2011-2013. PMID- 27275343 TI - Metabolic Syndrome and Cardiovascular Risk Factors in Obese Adolescent. AB - BACKGROUND: Childhood and adolescent obesity is associated with insulin resistance, abnormal glucose metabolism, hypertension, dyslipidemia, inflammation, liver disease, and compromised vascular function. The purpose of this study was to determine the prevalence of cardiovascular risk factor abnormalities and metabolic syndrome in a sample of obese adolescent as prevalence data might be helpful in improving engagement with obesity treatment in future. The high blood lipid levels and obesity are the main risk factors for cardio vascular diseases. Atherosclerotic process begins in childhood. AIM: This study aimed to investigate the relationship between obesity in adolescent and their blood lipids levels and blood glucose level. METHODS: This study was conducted with 100 adolescents of both gender age 12-17 years and body mass index (BMI) greater than 95th percentiles and 100 normal adolescents as control group. The blood samples were collected from all adolescents after overnight fasting (10 hours) to analyze blood lipids (Total cholesterol, high density lipoprotein, low density lipoprotein) and hematological profile (Hemoglobin, platelets and red blood cell, C reactive protein and fasting blood glucose. RESULTS: There were statistical difference between the two groups for red blood cells (P<0.001), Hemoglobin (P < 0.001) and platelets (P = 0.002), CRP (P = 0.02). Positive correlation was found between the two groups as regards total cholesterol (P = 0.0001), P value was positive for HDL (P = 0.005 and Atherogenic index P value was positive (P = 0.002). Positive correlation was found between the two group as regards fasting blood glucose (P = 0.001). CONCLUSION: Saturated fat was associated with elevated lipid levels in obese children. These results reinforce the importance of healthy dietary habits since child-hood in order to reduce the risks of cardiovascular diseases in adulthood. PMID- 27275344 TI - Characteristic of the Oxidative Stress in Blood of Patients in Dependence of Community-Acquired Pneumonia Severity. AB - BACKGROUND: At the present time the alternation of the oxidative metabolism is considered as one of the leading pathogenic mechanisms in the development and progression of community-acquired pneumonia (CAP). However the nature and direction of the oxidative protein changes in CAP patient's blood had been almost unexplored. AIM: To define oxidative and modified proteins in erythrocytes and blood plasma of CAP patients. MATERIAL AND METHODS: Blood plasma and erythrocytes obtained from: 42 patients with moderate severity pneumonia, 12 patients with grave severity pneumonia and 32 healthy volunteers. Content of advanced oxidation protein products, malondialdehyde and reactive carbonyl derivatives were estimated as indicators of the oxidative stress and oxidative damage of proteins. RESULTS: In patients with grave severity the level of oxidative proteins and MDA in erythrocytes exceeded both: control values and similar meanings in CAP patients with moderate severity. The further growth of MDA in this group patients' blood plasma was observed, but the level of oxidative proteins decreased in comparison with those in CAP patients with moderate severity. CONCLUSION: To sum up, our derived data show, that injury of erythrocytes' redox status and blood plasma components plays an essential role in development and progression CAP. PMID- 27275345 TI - Spontaneous Regression of an Incidental Spinal Meningioma. AB - AIM: The regression of meningioma has been reported in literature before. In spite of the fact that the regression may be involved by hemorrhage, calcification or some drugs withdrawal, it is rarely observed spontaneously. CASE REPORT: We report a 17 year old man with a cervical meningioma which was incidentally detected. In his cervical MRI an extradural, cranio-caudal contrast enchanced lesion at C2-C3 levels of the cervical spinal cord was detected. Despite the slight compression towards the spinal cord, he had no symptoms and refused any kind of surgical approach. The meningioma was followed by control MRI and it spontaneously regressed within six months. There were no signs of hemorrhage or calcification. CONCLUSION: Although it is a rare condition, the clinicians should consider that meningiomas especially incidentally diagnosed may be regressed spontaneously. PMID- 27275346 TI - Surgical Treatment of Anomalous Origin of Right Coronary Artery in a Patient with Mitral Stenosis. AB - BACKGROUND: An anomalous origin of the right coronary artery is rarely observed, with a reported incidence between 0.026% and 0.25%. This condition is often completely asymptomatic and is found incidentally during angiographic evaluation for other cardiac diseases. However some patients present with exertion angina or sudden death. Surgical treatment in patients with anomalous RCA is still controversial. Treatment can be conservative, angioplasty or surgery. CASE PRESENTATION: A 59-year-old man was admitted with severe mitral stenosis. He complained exertion and rest dyspnea, NYHA III class. He had sequels of embolic stroke, results of left atrial thrombus. Echocardiography showed calcified severe mitral stenosis with mitral orifice area of 1.1 square centimeters with PSPAP 60 mmHg and normal LV function. Routine coronary angiography before surgery showed aberrant origin of RCA from the left sinus of Valsalva with 90% stenosis at his origin. Multi-slice computed tomography proved the diagnosis of anomalous RCA arising from the left sinus of Valsalva and taking an inter-arterial course between the aorta and pulmonary artery. The patient underwent mitral valve replacement with mechanical St. Jude prosthesis No 29 and saphenous vein graft to RCA. We chose by-pass grafting techniques because after aortotomy, RCA was too close to LMCA, intramural course was too short and stenosis of RCA was outside of aortic wall. The patient's perioperative course was without complications and patient was discharged on the seventh postoperative day. CONCLUSION: Correction of anomalous of the origin of right coronary artery is mandatory in cases where patient has to be operated for other cardiac causes. PMID- 27275347 TI - Vesicoureteral Reflux Detected with (99m)Tc-DTPA Renal Scintigraphy during Evaluation of Renal Function. AB - BACKGROUND: Radionuclide techniques, as direct radionuclide cystography and (99m)Tc-DMSA scintigraphy, have been used in evaluation of vesicoureteral reflux (VUR) and reflux nephropathy (RN) in children. Dynamic (99m)Tc-DTPA scintigraphy is reserved for evaluation of differential renal function and obstruction in children, where hydronephrosis is detected by ultrasonography (US) pre- or postnatally. CASE REPORT: Six year old boy was prenatally diagnosed with bilateral hydronephrosis. Postnatal, severe bilateral VUR was detected by voiding urethrocytography. US and (99m)Tc-DTPA scintigraphy performed in the first month of life showed small left kidney that participated with 2% in the global renal function. Bilateral cutaneous ureterostomy has been performed in order to obtain good renal drainage and promote optimal renal growth. Twelve months later, classic antireflux procedure was done. Control (99m)Tc-DTPA scintigraphy, 5 ys after antireflux surgery, revealed persisting radioactivity during the diuretic phase, in the left kidney that indicated antireflux procedure failure with VUR reappearance. CONCLUSION: (99m)Tc-DTPA scintigraphy is the first method of choice for long-term monitoring of individual kidney function in children with VUR and other congenital urinary tract anomalies. Additionally, it can be used as indirect radionuclide cystography when rising of radioactivity in the kidney region, during the diuretic phase can indicate presence of VUR. PMID- 27275348 TI - Pure Motor Stroke Secondary to Cerebral Infarction of Recurrent Artery of Heubner after Mild Head Trauma: A Case Report. AB - BACKGROUND: The recurrent Heubner's artery is the distal part of the medial striate artery. Occlusion of the recurrent artery of Heubner, classically contralateral hemiparesis with fasciobrachiocrural predominance, is attributed to the occlusion of the recurrent artery of Heubner and is widely known as a stroke syndrome in adults. However, isolated occlusion of the deep perforating arteries following mild head trauma also occurs extremely rarely in childhood. CASE REPORT: Here we report the case of an 11-year-old boy with pure motor stroke. The brain MRI showed an acute ischemia in the recurrent artery of Heubner supply area following mild head trauma. His fasciobrachial hemiparesis and dysarthria were thought to be secondary to the stretching of deep perforating arteries leading to occlusion of the recurrent artery of Heubner. CONCLUSION: Post-traumatic pure motor ischemic stroke can be secondary to stretching of the deep perforating arteries especially in childhood. PMID- 27275349 TI - Endothelial Nitric Oxide Synthase T-786C Mutation, Prothrombin Gene Mutation (G 20210-A) and Protein S Deficiency Could Lead to Myocardial Infarction in a Very Young Male Adult. AB - INTRODUCTION: Myocardial infarction is a rare medical event in young people. The main reasons include congenital coronary abnormalities, coronary artery spasm, and coronary thrombosis due to hypercoagulable states (hereditary and acquired). AIM: We present a case of a young male adult with myocardial infarction caused by a combination of gene mutations and anticoagulation protein deficiency. CASE PRESENTATION: A 19 years old young man was admitted to our hospital complaining of chest pain during the last two weeks. The patient did not have any known cardiovascular risk factors, except a positive family anamnesis. Subacute inferior nonST segment myocardial infarction was diagnosed according to the patient's history, electrocardiographic and laboratory findings. Coronary angiography revealed suboclusive thrombus in the proximal, medial and distal part of the right coronary artery (TIMI 2). Percutaneous coronary intervention was performed. Anticoagulant and antiagregant therapy (heparin, acetilsalicilic acid and clopidogrel) according to protocol was started. The hospital stay was uneventful. Homozygous endothelial nitric oxid synthase (eNOS) T-786-C mutation, heterozygote prothrombin gene mutation (G-20210-A), and protein S deficiency were verified from the thrombophilia testing. Other trombophilic tests were normal. Three months after discharge from hospital another coronary angiography was performed. It revealed normal coronary arteries. Four years after the attack, the patient is free of symptoms and another cardiovascular event. CONCLUSION: Combination of genetic mutations and anticoagulation protein deficiency could be a reasonable cause for myocardial infarction in a very young male adult without any other cardiovascular risk factors. PMID- 27275350 TI - Long-Term Outcome after Rehabilitation of Bilateral Total Hip Arthroplasty in Renal Transplant Recipient - A Case Report. AB - INTRODUCTION: Total hip replacement is generally proposed for renal transplant patients with avascular osteonecrosis of the femoral head. PURPOSE: The purpose of the study is to report the long-term outcome after rehabilitation of bilateral total hip arthroplasty in a patient with renal transplantation suffering from avascular osteonecrosis of the both femoral heads. MATERIAL AND METHOD: The patient S.D, 49 years old at follow-up. Few months after renal transplantation, the patient had got avascular osteonecrosis of both femoral head. One year after transplantation the total hip arthroplasty for both hip joints were performed. Three years later repeat total hip arthroplasty surgery for left hip was performed. After any surgery intervention the patient was referred for inpatient rehabilitation. For clinical assessment the clinical findings and Harris Hip Score have been used. The rehabilitation program consisted of exercises, occupational therapy, and patient education. RESULTS: After any rehabilitation treatment the patient had improvement of clinical findings. At follow-up assessment outcome for both hip function was good - Harris Hip Score was 81 points. CONCLUSION: Rehabilitation is integral part of multidisciplinary treatment of renal transplant recipient after total hip arthroplasty. Regular exercise training of these patients is very important for improving of their long term outcome. PMID- 27275351 TI - Clinical Therapeutic Effects of the Application of Doxycycline in the Treatment of Periodontal Disease. AB - OBJECTIVE: To compare the therapeutic effects of the application of doxycycline full dose (100 mg) and sub-dose (20 mg) in the treatment of periodontal disease. MATERIAL AND METHODS: A total of 60 patients with periodontal disease were examined. Patients are divided into two groups: A) treated with antimicrobial dose of 100 mg doxycycline once daily for 30 days, and B) treated with 2 x 20 mg/day. doxycycline, during 75 days. Among all patients a conservative treatment was carried out and ordinated the proper dose doxycycline in total dose during treatment from 3 gr. Index of dental plaque by Loe-Sillness, index of gingival inflammation and gingival bleeding by Cowell were followed. RESULTS: Values of dental plaque in relation first examination, 10th, 20th day, 1 month and 2.5 months, showed that after 2.5 months, average value (x = 0.83) of dental plaque in second group is slightly less than the value (x = 0.93) of dental plaque in the first group. The average value (x = 0.17) of gingival inflammation in second group is significantly less than the value (x = 0.50) of gingival inflammation in the first group. The average value (x = 0.97) of gingival bleeding in patients from the first group was significantly higher than value(x = 0.37) of gingival bleeding in the second group. CONCLUSION: Patients whose therapy was helped by a sub-dose doxycycline demonstrated positive therapeutic effects on gingival inflammation and bleeding. PMID- 27275352 TI - The Effects of NBF Gingival Gel Application in the Treatment of the Erosive Lichen Planus: Case Report. AB - The therapy of erosive lichen planus (ELP) has been particular problem in the treatment of oral lesions. This case of ELP in male patient 29 years old was treated with topic application of the NBF gingival gel, three times a day after meal, previously rinsed with Clorhexidine gluconate 0.12%. After 5 days of treatment, initial improvements were recorded, and after two weeks of application of the NBF gingival gel we observed significant improvement. Clinical monitoring after the fifth day showed mild epithelialization of the eroded mucosa, yet still present erythematous base of the lesion. After the second week the erythema area was significantly reduced and the eroded surfaces of the mucosa were minimal, measured less than 0.5 mm. After the third week there were no erosions to detect on the oral mucosa, yet still present vague redness, which completely pulled after the fourth week. Treatment ended after the fifth week when the topical application of the NBF gingival gel was terminated, and therapy was done, and clinically achieved effects remained stable even after the third month of the treatment. Topic application of the NBF gingival gel with ELP patients showed positive clinical effects in relatively short time period. PMID- 27275353 TI - 3D Finite Element Study on: Bar Splinted Implants Supporting Partial Denture in the Reconstructed Mandible. AB - AIM: This study aimed to estimate the stress patterns induced by the masticatory loads on a removable prosthesis supported and retained by bar splinted implants placed in the reconstructed mandible with two different clip materials and without clip, in the fibula-jaw bone and prosthesis using finite element analysis. METHODS: Two 3D finite element models were constructed, that models components were modeled on commercial CAD/CAM software then assembled into finite element package. Vertical loads were applied simulating the masticatory forces unilaterally in the resected site and bilaterally in the central fossa of the lower first molar as 100N (tension and compression). Analysis was based on the assumption full osseointegration between different types of bones, and between implants and fibula while fixing the top surface of the TMJ in place. RESULTS: The metallic bar connecting the three implants is insensitive to the clips material. Its supporting implants showed typical behavior with maximum stress values at the neck region. Fibula and jaw bone showed stresses within physiologic, while clips material effect seems to be very small due to its relatively small size. CONCLUSION: Switching loading force direction from tensile to compression did-not change the stresses and deformations distribution, but reversed their sign from positive to negative. PMID- 27275354 TI - Misuse of Psychologically Active Substances of Convicts being in Prisons and their Treatment. AB - Due to the data of the Ministry of Justice of the Republic of Serbia, over 70% of persons being in prisons and serving their sentences are drug addicts, and 50% of them are drug users. In the European prisons, the percentage of persons using drugs in the entire prison population is 20-70%, and in the USA 70-80%, in the Australian prisons between 50 and 80% of the convicts in prisons are addicts of psychologically active substances. The results of our survey are pursuant to official statistics data for Serbia, the European countries, USA and Australia, since 80% of our convicts in prisons have misused psychologically active substances during the period of 30 days, the previous period before coming to these institutions. More than a half of our examinees (60%), misuses narcotics and alcohol occasionally or permanently, the alcohol users only 12.7%, and only narcotics 7.3% of the ones, meaning that a treatment of addiction disease should have a significant role in prevention of recidivism. PMID- 27275355 TI - Genomic Imprinting. AB - BACKGROUND: Genomic imprinting is the inheritance out of Mendelian borders. Many of inherited diseases and human development violates Mendelian law of inheritance, this way of inheriting is studied by epigenetics. AIM: The aim of this review is to analyze current opinions and options regarding to this way of inheriting. RESULTS: Epigenetics shows that gene expression undergoes changes more complex than modifications in the DNA sequence; it includes the environmental influence on the gametes before conception. Humans inherit two alleles from mother and father, both are functional for the majority of the genes, but sometimes one is turned off or "stamped" and doesn't show in offspring, that gene is imprinted. Imprinting means that that gene is silenced, and gene from other parent is expressed. The mechanisms for imprinting are still incompletely defined, but they involve epigenetic modifications that are erased and then reset during the creation of eggs and sperm. Genomic imprinting is a process of silencing genes through DNA methylation. The repressed allele is methylated, while the active allele is unmethylated. The most well-known conditions include Prader-Willi syndrome, and Angelman syndrome. Both of these syndromes can be caused by imprinting or other errors involving genes on the long arm of chromosome 15. CONCLUSIONS: Genomic imprinting and other epigenetic mechanisms such as environment is shown that plays role in offspring neurodevelopment and autism spectrum disorder. PMID- 27275356 TI - Application of a Small Molecule Radiopharmaceutical Concept to Improve Kinetics. AB - Recently, large molecules or nanoparticles are actively studied as radiopharmaceuticals. However, their kinetics is problematic because of a slow penetration through the capillaries and slow distribution to the target. To improve the kinetics, a two-step targeting method can be applied by using small molecules and very rapid copper-free click reaction. Although this method might have limitations such as internalization of the first targeted conjugate, it will provide high target-to-non-target ratio imaging of radiopharmaceuticals. PMID- 27275357 TI - Start from Scratch: the Prospect of Nuclear Cardiology. PMID- 27275359 TI - Instrumentation for Time-of-Flight Positron Emission Tomography. AB - Positron emission tomography (PET) is a molecular imaging modality that provides information at the molecular level. This system is composed of radiation detectors to detect incoming coincident annihilation gamma photons emitted from the radiopharmaceutical injected into a patient's body and uses these data to reconstruct images. A major trend in PET instrumentation is the development of time-of-flight positron emission tomography (ToF-PET). In ToF-PET, the time information (the instant the radiation is detected) is incorporated for image reconstruction. Therefore, precise and accurate timing recording is crucial in ToF-PET. ToF-PET leads to better localization of the annihilation event and thus results in overall improvement in the signal-to-noise ratio (SNR) of the reconstructed image. Several factors affect the timing performance of ToF-PET. In this article, the background, early research and recent advances in ToF-PET instrumentation are presented. Emphasis is placed on the various types of scintillators, photodetectors and electronic circuitry for use in ToF-PET, and their impact on timing resolution is discussed. PMID- 27275358 TI - Combination Radioimmunotherapy Approaches and Quantification of Immuno-PET. AB - Monoclonal antibodies (mAbs), which play a prominent role in cancer therapy, can interact with specific antigens on cancer cells, thereby enhancing the patient's immune response via various mechanisms, or mAbs can act against cell growth factors and, thereby, arrest the proliferation of tumor cells. Radionuclide labeled mAbs, which are used in radioimmunotherapy (RIT), are effective for cancer treatment because tumor associated-mAbs linked to cytotoxic radionuclides can selectively bind to tumor antigens and release targeted cytotoxic radiation. Immunological positron emission tomography (immuno-PET), which is the combination of PET with mAb, is an attractive option for improving tumor detection and mAb quantification. However, RIT remains a challenge because of the limited delivery of mAb into tumors. The transport and uptake of mAb into tumors is slow and heterogeneous. The tumor microenvironment contributed to the limited delivery of the mAb. During the delivery process of mAb to tumor, mechanical drug resistance such as collagen distribution or physiological drug resistance such as high intestinal pressure or absence of lymphatic vessel would be the limited factor of mAb delivery to the tumor at a potentially lethal mAb concentration. When alpha emitter-labeled mAbs were used, deeper penetration of alpha-emitter-labeled mAb inside tumors was more important because of the short range of the alpha emitter. Therefore, combination therapy strategies aimed at improving mAb tumor penetration and accumulation would be beneficial for maximizing their therapeutic efficacy against solid tumors. PMID- 27275360 TI - A Comparison Study of Esophageal Findings on (18)F-FDG PET/CT and Esophagogastroduodenoscopy. AB - PURPOSE: The aim of this study was to compare the esophageal findings of 2-deoxy 2-[(18)F]fluoro-d-glucose positron emission tomography-computed tomography ((18)F FDG PET/CT) and esophagogastroduodenoscopy (EGD). METHODS: We retrospectively reviewed (18)F-FDG PET/CT and EGD findings of 369 subjects who underwent medical examination between January 2014 and December 2014. The range and intensity of esophageal (18)F-FDG uptake were visually analyzed. The maximum standardized uptake value (SUVmax) of the esophagus and around the esophagogastric (EG) junction was measured. EGD results were provided by the gastroenterologist. We compared the esophageal findings obtained using (18)F-FDG PET/CT and EGD. RESULTS: There were typical linear FDG uptakes in (18)F-FDG PET/CT patients who underwent EGD the same day. In visual analysis of the range and intensity of the (18)F-FDG uptake, the patients who underwent (18)F-FDG PET/CT and EGD on the same day showed relatively diffuse and discernible (18)F-FDG uptake in the esophagus. Reflux esophagitis was diagnosed in 59 subjects, and 27 of these were classified as higher than Los Angeles classification A. With an increasing degree of reflux esophagitis observed on EGD, the SUVmax in the esophagus and around the EG junction was also increased. CONCLUSION: Our study showed that FDG uptake at the esophagus or the EG junction might be clinically significantly related to esophagitis. However, EGD performed before (18)F-FDG PET/CT on the same day may affect the esophageal (18)F-FDG uptake. PMID- 27275361 TI - Clinical Usefulness of F-18 FDG PET/CT in Papillary Thyroid Cancer with Negative Radioiodine Scan and Elevated Thyroglobulin Level or Positive Anti-thyroglobulin Antibody. AB - PURPOSE: Elevated thyroglobulin (Tg) levels, along with a negative radioiodine scan, present a clinical problem for the diagnosis of recurrence in papillary thyroid cancer (PTC) patients. The purpose of this study was to assess (1) the usefulness of (18)F-fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) for PTC patients with negative diagnostic radioiodine scan and elevated serum Tg level or positive anti-thyroglobulin antibody (TgAb), and (2) the effect of endogenous thyroid stimulating hormone (TSH) stimulation (ETS) on detecting recurrence in these circumstances. METHODS: Eighty-four patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb under ETS were included. Correlation with clinicopathological features and recurrence, detectability of FDG PET/CT and cut-off value of serum Tg for recurrence in PTC patients with these circumstance were assessed. In addition, detectability of F-18 FDG PET/CT under ETS and suppression were compared. RESULTS: In Cox regression analysis, only serum Tg level was significantly associated with recurrence (P < 0.001, HR = 1.13; 95 % CI, 1.061 1.208). The cut-off level of Tg was 21.5 ng/mL (AUC, 0.919; P < 0.001) for discriminating the recurrence in the patients with positive PET/CT finding. The sensitivity, specificity, PPV, NPV, and accuracy of F-18 FDG PET/CT for detecting recurrence were 64 %, 94 %, 86 %, 81 %, and 83 %. In the analysis of F-18 FDG PET/CT under ETS, the sensitivity, specificity, PPV, NPV and accuracy was 64 %, 94 %, 88 %, 81 % and 83 %. Those under TSH suppression were 67 %, 92 %, 80 %, 85 % and 83 %. CONCLUSIONS: F-18 FDG PET/CT, although less sensitive, showed high specificity, PPV, NPV, and accuracy and therefore can be useful for the patients with negative diagnostic radioiodine scan and elevated serum Tg or positive TgAb. In addition, FDG PET/CT under ETS does not seem to have an additive role in detecting recurrence in these patients. PMID- 27275362 TI - Correlation of Uptake Patterns on Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) and Treatment Response in Patients with Knee Pain. AB - PURPOSE: To determine whether treatment response in patients with knee pain could be predicted using uptake patterns on single-photon emission computed tomography/computed tomography (SPECT/CT) images. METHODS: Ninety-five patients with knee pain who had undergone SPECT/CT were included in this retrospective study. Subjects were divided into three groups: increased focal uptake (FTU), increased irregular tracer uptake (ITU), and no tracer uptake (NTU). A numeric rating scale (NRS-11) assessed pain intensity. We analyzed the association between uptake patterns and treatment response using Pearson's chi-square test and Fisher's exact test. Uptake was quantified from SPECT/CT with region of interest (ROI) counting, and an intraclass correlation coefficient (ICC) calculated agreement. We used Student's t-test to calculate statistically significant differences of counts between groups and the Pearson correlation to measure the relationship between counts and initial NRS-1k1. Multivariate logistic regression analysis determined which variables were significantly associated with uptake. RESULTS: The FTU group included 32 patients; ITU, 39; and NTU, 24. With conservative management, 64 % of patients with increased tracer uptake (TU, both focal and irregular) and 36 % with NTU showed positive response. Conservative treatment response of FTU was better than NTU, but did not differ from that of ITU. Conservative treatment response of TU was significantly different from that of NTU (OR 3.1; p = 0.036). Moderate positive correlation was observed between ITU and initial NRS-11. Age and initial NRS-11 significantly predicted uptake. CONCLUSIONS: Patients with uptake in their knee(s) on SPECT/CT showed positive treatment response under conservative treatment. PMID- 27275363 TI - Clinical Value of a One-Stop-Shop Low-Dose Lung Screening Combined with (18)F-FDG PET/CT for the Detection of Metastatic Lung Nodules from Colorectal Cancer. AB - PURPOSE: The aim of this study was to evaluate the clinical usefulness of additional low-dose high-resolution lung computed tomography (LD-HRCT) combined with (18)F-fluoro-2-deoxyglucose positron emission tomography with CT ((18)F-FDG PET/CT) compared with conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer. METHODS: From January 2011 to September 2011, 649 patients with colorectal cancer underwent additional LD-HRCT at maximum inspiration combined with (18)F-FDG PET/CT. Forty five patients were finally diagnosed to have lung metastasis based on histopathologic study or clinical follow-up. Twenty-five of the 45 patients had <=5 metastatic lung nodules and the other 20 patients had >5 metastatic nodules. One hundred and twenty nodules in the 25 patients with <=5 nodules were evaluated by conventional lung setting image of (18)F-FDG PET/CT and by additional LD-HRCT respectively. Sensitivities, specificities, diagnostic accuracies, positive predictive values (PPVs), and negative predictive values (NPVs) of conventional lung setting image of (18)F-FDG PET/CT and additional LD-HRCT were calculated using standard formulae. The McNemar test and receiver-operating characteristic (ROC) analysis were performed. RESULTS: Of the 120 nodules in the 25 patients with <=5 metastatic lung nodules, 66 nodules were diagnosed as metastatic. Eleven of the 66 nodules were confirmed histopathologically and the others were diagnosed by clinical follow-up. Conventional lung setting image of (18)F-FDG PET/CT detected 40 of the 66 nodules and additional LD-HRCT detected 55 nodules. All 15 nodules missed by conventional lung setting imaging but detected by additional LD-HRCT were <1 cm in size. The sensitivity, specificity, and diagnostic accuracy of the modalities were 60.6 %, 85.2 %, and 71.1 % for conventional lung setting image and 83.3 %, 88.9 %, and 85.8 % for additional LD HRCT. By ROC analysis, the area under the ROC curve (AUC) of conventional lung setting image and additional LD-HRCT were 0.712 and 0.827 respectively. CONCLUSION: Additional LD-HRCT with maximum inspiration was superior to conventional lung setting image of (18)F-FDG PET/CT for the detection of metastatic lung nodules from colorectal cancer (P < 0.05). PMID- 27275364 TI - Correlation Between Apparent Diffusion Coefficients and Standardized Uptake Values in Hybrid (18)F-FDG PET/MR: Preliminary Results in Rectal Cancer. AB - PURPOSE: Fluorine-18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI) share the same role in clinical oncology and it is feasible to obtain the standardized uptake value (SUV) and apparent diffusion coefficient (ADC) simultaneously by emerging the hybrid positron emission tomography/magnetic resonance (PET/MR). This study investigated the correlation between the ADCs of rectal cancer lesions and their SUVs derived from hybrid PET/MR. METHODS: Nine patients with histologically proven rectal adenocarcinoma (5 men, 4 women; mean age, 70 +/- 15.91 years) underwent torso (18)F-FDG PET/CT and regional hybrid (18)F-FDG PET/MR sequentially. A fixed threshold value of 40 % of maximum uptake was used to determine tumor volume of interest (VOI) on PET image; SUVmax, SUVpeak, and SUVmean were calculated automatically. A single freehand region of interest (ROI) was drawn on high b-value (b1000) DWI image and copied to corresponding ADC map to determine the ADCmean of rectal cancer lesion. Spearman's rank correlation coefficient (rho) was calculated to determine the correlation between SUVs and ADC values. RESULTS: SUVmax, SUVpeak, and SUVmean derived by hybrid PET/MR were 12.35 +/- 4.66 (mean +/- standard deviation), 9.66 +/- 3.15 and 7.41 +/- 2.54, respectively. The ADCmean value of rectal cancer lesions was 1.02 +/- 0.08 * 10( 3)mm(2)/s. ADCmean was significantly and inversely correlated with SUV values (SUVmax, rho = -0.95, p < 0.001; SUVpeak, rho = -0.93, p < 0.001; SUVmean, rho = 0.91, p = 0.001). CONCLUSIONS: This preliminary hybrid PET/MR study demonstrates a significant inverse correlation exists between metabolic activity on (18)F-FDG PET and water diffusion on DWI in rectal cancer. PMID- 27275365 TI - Growth Arrest Line Mimicking Lymphoma Involvement: The Findings of (99m)Tc-MDP Bone SPECT/CT and Serial Bone Scan in a Child with Non-Hodgkin's Lymphoma. AB - Growth arrest lines appear as dense sclerotic lines parallel to the growth plate of long bones on radiography. We describe the case of a 9-year-old female with growth arrest lines initially masquerading as lymphoma involvement on (99m)Tc-MDP bone scintigraphy who had been treated with chemotherapy for non-Hodgkin's lymphoma about 3 years previously. Subsequent regional bone SPECT/CT clearly diagnosed the growth arrest lines, and retrograde review of previous bone scintigraphy demonstrated line migration in this patient. Growth arrest lines should be considered a possible diagnosis on bone scintigraphy, especially in the surveillance of children who have experienced severe childhood infections, malnutrition, immobilization, or treatment with immunosuppressive or chemotherapeutic drugs that may inhibit bone growth. PMID- 27275366 TI - A Rare Case of Multilocular Thymic Cyst with Follicular Lymphoid Hyperplasia: Radiologic and Histopathologic Features. AB - Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose. PMID- 27275367 TI - Value of (99m)Tc-Technegas SPECT/CT for Localization of Alveolar-pleural Fistulas. PMID- 27275368 TI - Adrenocortical Carcinoma: False Positive in an I-123 Metaiodobenzylguanedine Scan. PMID- 27275369 TI - Intramedullary Spinal Cord Metastasis from Breast Cancer Mimicking Delayed Radiation Myelopathy: Detection With (18)F-FDG PET/CT. PMID- 27275370 TI - 18F-FDG PET/CT for Detecting Sarcoma of the Aorta in a Patient with Takayasu Arteritis. PMID- 27275371 TI - Lymphoscintigraphy SPECT/CT: Instrumental Navigator in Repair of Thoracic Duct Injury. PMID- 27275372 TI - Primary Rectal Adenocarcinoma Metastasizing to Bilateral Breasts - a Rare Case Demonstrated by (18) F-FDG PET/CT. PMID- 27275373 TI - Inferior Vena Cava Filter Thrombus: a Possible Cause of an Unanticipated Finding of (99m)Tc-labeled Red Blood Cell Scintigraphy. AB - (99m)Tc-labeled red blood cell scintigraphy, a sensitive and specific diagnostic test, is useful for patients suspected of suffering from active gastrointestinal bleeding. This study follows a case of a patient who was suspected of gastrointestinal bleeding after an inferior vena cava filter was inserted due to a deep vein thrombosis of the femoral vein. To evaluate an exact focus of bleeding, (99m)Tc-labeled red blood cell scintigraphy was executed. Herein, an unanticipated finding of (99m)Tc-labeled red blood cell scintigraphy probably due to a thrombus on the inferior vena cava filter is reported. PMID- 27275374 TI - Detection of Synchronous Parathyroid Adenoma and Breast Cancer with (18)F Fluorocholine PET-CT. PMID- 27275375 TI - Towards a fourth spatial dimension of brain activity. AB - Current advances in neurosciences deal with the functional architecture of the central nervous system, paving the way for general theories that improve our understanding of brain activity. From topology, a strong concept comes into play in understanding brain functions, namely, the 4D space of a "hypersphere's torus", undetectable by observers living in a 3D world. The torus may be compared with a video game with biplanes in aerial combat: when a biplane flies off one edge of gaming display, it does not crash but rather it comes back from the opposite edge of the screen. Our thoughts exhibit similar behaviour, i.e. the unique ability to connect past, present and future events in a single, coherent picture as if we were allowed to watch the three screens of past-present-future "glued" together in a mental kaleidoscope. Here we hypothesize that brain functions are embedded in a imperceptible fourth spatial dimension and propose a method to empirically assess its presence. Neuroimaging fMRI series can be evaluated, looking for the topological hallmark of the presence of a fourth dimension. Indeed, there is a typical feature which reveal the existence of a functional hypersphere: the simultaneous activation of areas opposite each other on the 3D cortical surface. Our suggestion-substantiated by recent findings-that brain activity takes place on a closed, donut-like trajectory helps to solve long standing mysteries concerning our psychological activities, such as mind wandering, memory retrieval, consciousness and dreaming state. PMID- 27275376 TI - An exploration of spatial auditory BCI paradigms with different sounds: music notes versus beeps. AB - Visual brain-computer interfaces (BCIs) are not suitable for people who cannot reliably maintain their eye gaze. Considering that this group usually maintains audition, an auditory based BCI may be a good choice for them. In this paper, we explore two auditory patterns: (1) a pattern utilizing symmetrical spatial cues with multiple frequency beeps [called the high low medium (HLM) pattern], and (2) a pattern utilizing non-symmetrical spatial cues with six tones derived from the diatonic scale [called the diatonic scale (DS) pattern]. These two patterns are compared to each other in terms of accuracy to determine which auditory pattern is better. The HLM pattern uses three different frequency beeps and has a symmetrical spatial distribution. The DS pattern uses six spoken stimuli, which are six notes solmizated as "do", "re", "mi", "fa", "sol" and "la", and derived from the diatonic scale. These six sounds are distributed to six, spatially distributed, speakers. Thus, we compare a BCI paradigm using beeps with another BCI paradigm using tones on the diatonic scale, when the stimuli are spatially distributed. Although no significant differences are found between the ERPs, the HLM pattern performs better than the DS pattern: the online accuracy achieved with the HLM pattern is significantly higher than that achieved with the DS pattern (p = 0.0028). PMID- 27275377 TI - Temporal properties of dual-peak responses of mouse retinal ganglion cells and effects of inhibitory pathways. AB - Dual-peak responses of retinal ganglion cells (RGCs) are observed in various species, previous researches suggested that both response peaks were involved in retinal information coding. In the present study, we investigated the temporal properties of the dual-peak responses recorded in mouse RGCs elicited by spatially homogeneous light flashes and the effect of the inhibitory inputs mediated by GABAergic and/or glycinergic pathways. We found that the two peaks in the dual-peak responses exhibited distinct temporal dynamics, similar to that of short-latency and long-latency single-peak responses respectively. Pharmacological studies demonstrated that the application of exogenous GABA or glycine greatly suppressed or even eliminated the second peak of the cells' firing activities, while little change was induced in the first peak. Co application of glycine and GABA led to complete elimination of the second peak. Moreover, application of picrotoxin or strychnine induced dual-peak responses in some cells with transient responses by unmasking a second response phase. These results suggest that both GABAergic and glycinergic pathways are involved in the dual-peak responses of the mouse RGCs, and the two response peaks may arise from distinct pathways that would converge on the ganglion cells. PMID- 27275378 TI - Hemispheric asymmetry non-linear analysis of EEG during emotional responses from idiopathic Parkinson's disease patients. AB - Recent studies show right hemisphere has a unique contribution to emotion processing. The present study investigated EEG using non-linear measures during emotional processing in PD patients with respect to motor symptom asymmetry (i.e., most affected body side). We recorded 14-channel wireless EEGs from 20 PD patients and 10 healthy age-matched controls (HC) by eliciting emotions such as happiness, sadness, fear, anger, surprise and disgust. PD patients were divided into two groups, based on most affected body side and unilateral motor symptom severity: left side-affected (LPD, n = 10) or right side-affected PD patients (RPD, n = 10). Nonlinear analysis of these emotional EEGs were performed by using approximate entropy, correlation dimension, detrended fluctuation analysis, fractal dimension, higher order spectra, hurst exponent (HE), largest Lyapunov exponent and sample entropy. The extracted features were ranked using analysis of variance based on F value. The ranked features were then fed into classifiers namely fuzzy K-nearest neighbor and support vector machine to obtain optimal performance using minimum number of features. From the experimental results, we found that (a) classification performance across all frequency bands performed well in recognizing emotional states of LPD, RPD, and HC; (b) the emotion specific features were mainly related to higher frequency bands; and (c) predominantly LPD patients (inferred right-hemisphere pathology) were more impaired in emotion processing compared to RPD, as showed by a poorer classification performance. The results suggest that asymmetric neuronal degeneration in PD patients may contribute to the impairment of emotional communication. PMID- 27275379 TI - Two generalized algorithms measuring phase-amplitude cross-frequency coupling in neuronal oscillations network. AB - An increasing number of studies pays attention to cross-frequency coupling in neuronal oscillations network, as it is considered to play an important role in exchanging and integrating of information. In this study, two generalized algorithms, phase-amplitude coupling-evolution map approach and phase-amplitude coupling-conditional mutual information which have been developed and applied originally in an identical rhythm, are generalized to measure cross-frequency coupling. The effectiveness of quantitatively distinguishing the changes of coupling strength from the measurement of phase-amplitude coupling (PAC) is demonstrated based on simulation data. The data suggest that the generalized algorithms are able to effectively evaluate the strength of PAC, which are consistent with those traditional approaches, such as PAC-PLV and PAC-MI. Experimental data, which are local field potentials obtained from anaesthetized SD rats, have also been analyzed by these two generalized approaches. The data show that the theta-low gamma PAC in the hippocampal CA3-CA1 network is significantly decreased in the glioma group compared to that in the control group. The results, obtained from either simulation data or real experimental signals, are consistent with that of those traditional approaches PAC-MI and PAC PLV. It may be considered as a proper indicator for the cross frequency coupling in sub-network, such as the hippocampal CA3 and CA1. PMID- 27275380 TI - Functional connectivity between prefrontal cortex and striatum estimated by phase locking value. AB - The interplay between the prefrontal cortex (PFC) and striatum has an important role in cognitive processes. To investigate interactive functions between the two areas in reward processing, we recorded local field potentials (LFPs) simultaneously from the two areas of two monkeys performing a reward prediction task (large reward vs small reward). The power of the LFPs was calculated in three frequency bands: the beta band (15-29 Hz), the low gamma band (30-49 Hz), and the high gamma band (50-100 Hz). We found that both the PFC and striatum encoded the reward information in the beta band. The reward information was also found in the high gamma band in the PFC, not in the striatum. We further calculated the phase-locking value (PLV) between two LFP signals to measure the phase synchrony between the PFC and striatum. It was found that significant differences occurred between PLVs in different task periods and in different frequency bands. The PLVs in small reward condition were significant higher than that in large reward condition in the beta band. In contrast, the PLVs in the high gamma band were stronger in large reward trials than in small trials. These results suggested that the functional connectivity between the PFC and striatum depended on the task periods and reward conditions. The beta synchrony between the PFC and striatum may regulate behavioral outputs of the monkeys in the small reward condition. PMID- 27275381 TI - Saliency computation via whitened frequency band selection. AB - Many saliency computational models have been proposed to simulate bottom-up visual attention mechanism of human visual system. However, most of them only deal with certain kinds of images or aim at specific applications. In fact, human beings have the ability to correctly select attentive focuses of objects with arbitrary sizes within any scenes. This paper proposes a new bottom-up computational model from the perspective of frequency domain based on the biological discovery of non-Classical Receptive Field (nCRF) in the retina. A saliency map can be obtained according to the idea of Extended Classical Receptive Field. The model is composed of three major steps: firstly decompose the input image into several feature maps representing different frequency bands that cover the whole frequency domain by utilizing Gabor wavelet. Secondly, whiten the feature maps to highlight the embedded saliency information. Thirdly, select some optimal maps, simulating the response of receptive field especially nCRF, to generate the saliency map. Experimental results show that the proposed algorithm is able to work with stable effect and outstanding performance in a variety of situations as human beings do and is adaptive to both psychological patterns and natural images. Beyond that, biological plausibility of nCRF and Gabor wavelet transform make this approach reliable. PMID- 27275382 TI - Decreased gene expression activity as a result of a mutation in the calreticulin gene promoter in a family case of schizoaffective disorder. AB - Accumulating evidence of population association studies support the hypothesis that the high heritability of major psychiatric disorders is a combination of relatively common alleles of modest effect, and rare alleles some with relatively larger effects. We have previously reported low frequency mutations in the proximal promoter of the human calreticulin (CALR) gene that co-occur with the spectrum of major psychiatric disorders. One of those mutations at -205C>T (rs556992558) was detected in an isolate case of schizoaffective disorder. In the current study, the functional implication of mutation -205T is studied in the human neuronal cell lines LAN-5, BE(2)-C and HEK-293. In contrast with other mutations in the promoter region which increase gene expression activity, the 205T mutation significantly decreased gene expression in those cell lines in comparison with the wild-type -205C nucleotide (p < 0.000001, p < 0.0005, and p < 0.017, respectively). Treatment of the cell lines with the mood-stabilizing drug, valproic acid (VPA) resulted in differential gene expression activity in the mutant -205T versus the wild-type -205C construct. VPA increased gene expression activity in both constructs, while a significantly higher expression activity was observed in the mutant construct (p < 0.01), indicative of the creation of a positive effector binding site for VPA as a result of the -205T mutation. We conclude that deviation from normalcy in the level of CALR in either direction is associated with major psychiatric disorders. PMID- 27275383 TI - Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. AB - BACKGROUND: Colorectal cancers (CRC) are associated with perturbations in cellular amino acids, nucleotides, pentose-phosphate pathway carbohydrates, and glycolytic, gluconeogenic, and tricarboxylic acid intermediates. A non-targeted global metabolome approach was utilized for exploring human CRC, adjacent mucosa, and stool. In this pilot study, we identified metabolite profile differences between CRC and adjacent mucosa from patients undergoing colonic resection. Metabolic pathway analyses further revealed relationships between complex networks of metabolites. METHODS: Seventeen CRC patients participated in this pilot study and provided CRC, adjacent mucosa ~10 cm proximal to the tumor, and stool. Metabolomes were analyzed by gas chromatography-mass spectrometry (GC/MS) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). All of the library standard identifications were confirmed and further analyzed via MetaboLync(TM) for metabolic network interactions. RESULTS: There were a total of 728 distinct metabolites identified from colonic tissue and stool matrices. Nineteen metabolites significantly distinguished CRC from adjacent mucosa in our patient-matched cohort. Glucose-6-phosphate and fructose-6-phosphate demonstrated 0.64-fold and 0.75-fold lower expression in CRC compared to mucosa, respectively, whereas isobar: betaine aldehyde, N-methyldiethanolamine, and adenylosuccinate had 2.68-fold and 1.88-fold higher relative abundance in CRC. Eleven of the 19 metabolites had not previously been reported for CRC relevance. Metabolic pathway analysis revealed significant perturbations of short-chain fatty acid metabolism, fructose, mannose, and galactose metabolism, and glycolytic, gluconeogenic, and pyruvate metabolism. In comparison to the 500 stool metabolites identified from human CRC patients, only 215 of those stool metabolites were also detected in tissue. This CRC and stool metabolome investigation identified novel metabolites that may serve as key small molecules in CRC pathogenesis, confirmed the results from previously reported CRC metabolome studies, and showed networks for metabolic pathway aberrations. In addition, we found differences between the CRC and stool metabolomes. CONCLUSIONS: Stool metabolite profiles were limited for direct associations with CRC and adjacent mucosa, yet metabolic pathways were conserved across both matrices. Larger patient-matched CRC, adjacent non cancerous colonic mucosa, and stool cohort studies for metabolite profiling are needed to validate these small molecule differences and metabolic pathway aberrations for clinical application to CRC control, treatment, and prevention. PMID- 27275384 TI - Fluticasone furoate/Vilanterol 92/22 MUg once-a-day vs Beclomethasone dipropionate/ Formoterol 100/6 MUg b.i.d.: a 12-week cost analysis in mild-to moderate asthma. AB - BACKGROUND: Asthma is a disease with high cost for the National Health Service. Two of the most recent LABA/ICS combinations for persistent bronchial asthma are Beclomethasone dipropionate/Formoterol (B/F) delivered via the Nexthaler device and Fluticasone furoate/Vilanterol (F/V) delivered via the Ellipta device. No comparison has been carried out yet in terms of cost analysis in asthma, to our knowledge. Aim of the present monocentric, observational, retrospective study was to calculate and compare the costs of mild-to-moderate asthma patients assuming B/F 100/6 MUg b.i.d. to those of patients assuming F/V 92/22 MUg once-a-day over a 12-week treatment period from the Italian National Health Service perspective. METHODS: Data were obtained automatically and anonymously from the institutional database of the Lung Unit of the Specialist Medical Centre (CEMS), Verona, Italy, UNI EN ISO 9001-2008 validated. FEV1 values, number of relapses, healthcare resources as hospitalizations due to asthma relapses, days of hospitalization, general practitioner (GP), specialist visits, and days of inactivity, were recorded over the study period together with the use of extra medications (systemic steroids and antibiotics). In order to compare the outcomes achieved in both groups, the propensity score matching method was used in STATA, and statistical significance was accepted for p < 0.05. RESULTS: Clinical data of 77 patients treated with B/F b.i.d (Group A) and of 40 patients treated with F/V 92/22 MUg once-a-day (Group B) were selected. The PS-matching process, designed as matching on the baseline covariates, gender, age, FEV1 and comorbidities, returned a cohort of 40 group A patients of the entire cohort matched with 40 patients of group B, fully comparable for demographics and clinical characteristics. In the PS-matched cohort, the mean (+/-SE) number of relapses per patient during the follow-up was 0.53 (+/-0.12) in group A and 0.28 (+/-0.07) in group B. In group A, n = 25 (62.50 %), n = 9 (22.50 %), and n = 6 (15 %) patients had 0, 1, 2 relapses, respectively. In group B, n = 29 (72.50 %), and n = 11 (27.50 %) had 0 and 1 relapse, respectively. Over the study period, the average number of hospitalizations per patient was 0.15 (+/-0.06), with 0.28 (+/ 0.12) days of hospitalization in group A, and 0.08 (+/-0.04) with 0.08 (+/-0.04) days of hospitalization in group B, respectively. The difference between the two groups in terms of FEV1(L) improvement vs baseline was 0.11 in favour of group B (p = 0.007). When results were compared, the improvement in lung function obtained in group B proved significantly higher both in terms of absolute FEV1 and of FEV1 % predicted. The mean (+/-SE) cost of hospitalizations per patient was ? 345.30 (+/-133.23) in group A and ? 172.65 (+/-98.18) in group B, respectively, with a mean not significant difference of - ? 172.65 in favour of group B (p = 0.9). In particular, the mean (+/-SE) cost for visits per patient was ? 26.82 (+/-3.73) in group A and ? 11.36 (+/-2.30) in group B (p = 0.002), and the mean cost for rescue medications per patient was ? 35.24 (+/-6.93) in group A, and ? 18.73 (+/-3.38) in group B, respectively (p = 0.05). CONCLUSIONS: Even if both ICS/LABA combinations were checked over a limited period of time, they seem characterized by a different profile in terms of effect on lung function and economic impact on mild-to-moderate asthma. The once-daily inhalation of combined Fluticasone furoate/Vilanterol 92/22 MUg showed the potential for enhanced clinical outcomes and reduced costs when compared to Beclomethasone dipropionate/Formoterol 100/6 MUg b.i.d. PMID- 27275394 TI - Cautionary optimism: caffeine and Parkinson's disease risk. AB - Most Parkinson's disease (PD) patients present without known family history and without a diagnosed prodromal phase, underscoring the difficulty of employing primary (neuroprevention) and secondary (neuroprotection) preventions. In cases of monogenic forms, however, potential gene-carrying family members of a proband could engage in neuroprevention, such as exercise or diet modifications, to attenuate the risk of, or delay, disease development. However, a historical lack of recognized disease-modifying interventions has limited clinicians' ability to recommend reliable preventive measures in caring for at-risk populations. We briefly analyze the first retrospective study to examine caffeine consumption and PD risk in a LRRK2 R1628P cohort. PMID- 27275395 TI - On Edge: the impact of race-related vigilance on obesity status in African Americans. AB - OBJECTIVE: Nearly half of African-Americans are classified as obese. Perceived racism has been associated with obesity, yet the internal experiences of racism have received little attention. African Americans who face racism may "ready themselves" to cope through survival strategies, including race-related vigilance. This study explores the association between race-related vigilance and obesity in African Americans. DESIGN AND METHODS: The Reactions to Race module of the Behavioral Risk Factor Surveillance Survey (years 2002-2010) was used. Our sample size consisted of 12,214 African-Americans. Race-related vigilance was assessed as: "How often do you think about your race?" and classified as: never, < daily, daily, and > daily. Obesity was dichotomized as body mass index (BMI) >=30 kg/m2 vs. < 30 kg/m2 using self-reported weight and height. Multivariable logistic models assessed the association between race-related vigilance and obesity. RESULTS: Seventeen percent of respondents reported thinking about their race > daily; 14% daily; 31% < daily, and 39% reported never thinking about their race. Compared to those who reported never thinking about their race, the adjusted odds of obesity were 0.91, 95% CI: 0.72-1.15 among those thinking about their race daily. CONCLUSIONS: Frequently thinking about one's race was a risk factor for obesity in African-Americans in this study. Internalized impacts of racism captured through race-related vigilance may be particularly detrimental to African Americans, driving their risk for obesity. PMID- 27275397 TI - The siRNA-Mediated Down-Regulation of Vascular Endothelial Growth Factor Receptor1. AB - BACKGROUND: Angiogenesis is an important biological process involved in the proliferation of endothelial cells, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is considered as a prominent regulator of angiogenesis which exerts the aforementioned effect(s) through its respective receptors (VEGFR1 and VEGFR2). VEGF receptors are targeted as a therapeutic candidate for cancer growth inhibition. RNAi as a new and promising strategy has provided a useful means to specifically suppress gene expression in cancer cells. OBJECTIVES: The current study aimed to down-regulate expression of the VEGFR1 using siRNA. MATERIALS AND METHODS: This experimental study designed specific siRNAs against VEGFR1. Total RNA was extracted from human umbilical vain endothelial cell (HUVEC) and subsequently cDNA was synthetized. PCR was performed using specific primers to amplify the target gene. After double digestion and purification, the gene was cloned into pEFGP-N1 expression vector. Then, AGS cells were transfected with recombinant pEGFP-N1 using lipofectamin. The gene expression and down-regulation were evaluated by fluorescence scanning, reverse transcription PCR (RT-PCR) and Western blot techniques. RESULTS: Fluorescent scanning, RT-PCR (27.68%) and western blot analysis (31.06%) showed that the expression of VEGFR1 was suppressed effectively. CONCLUSIONS: The results of the current study showed that specifically designed siRNA can be considered as an appropriate strategy to suppress gene expression and might be a promising tool to prevent angiogenesis. PMID- 27275396 TI - Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration. AB - In vertebrates, 14-3-3 proteins form a family of seven highly conserved isoforms with chaperone activity, which bind phosphorylated substrates mostly involved in regulatory and checkpoint pathways. 14-3-3 proteins are the most abundant protein in the brain and are abundantly found in the cerebrospinal fluid in neurodegenerative diseases, suggesting a critical role in neuron physiology and death. Here we show that 14-3-3eta-deficient mice displayed auditory impairment accompanied by cochlear hair cells' degeneration. We show that 14-3-3eta is highly expressed in the outer and inner hair cells, spiral ganglion neurons of cochlea and retinal ganglion cells. Screening of YWHAH, the gene encoding the 14 3-3eta isoform, in non-syndromic and syndromic deafness, revealed seven non synonymous variants never reported before. Among them, two were predicted to be damaging in families with syndromic deafness. In vitro, variants of YWHAH induce mild mitochondrial fragmentation and severe susceptibility to apoptosis, in agreement with a reduced capacity of mutated 14-3-3eta to bind the pro-apoptotic Bad protein. This study demonstrates that YWHAH variants can have a substantial effect on 14-3-3eta function and that 14-3-3eta could be a critical factor in the survival of outer hair cells. PMID- 27275398 TI - Prevention and Treatment of Flatulence From a Traditional Persian Medicine Perspective. AB - CONTEXT: The feeling of abdominal fullness, bloating, and movement of gas in the abdomen is a very uncomfortable sensation termed flatulence. Since flatulence is one of the most common gastrointestinal symptoms that is bothersome to patients, it is important to identify effective methods to resolve this issue. In modern medicine, management of flatulence is often not satisfactory. On the other hand, traditional systems of medicine can be considered good potential sources to find new approaches for preventing and treating flatulence. The aim of this study is to review flatulence treatments from a traditional Persian medicine (TPM) viewpoint. EVIDENCE ACQUISITION: In this study, the reasons for flatulence and methods for its prevention and treatment are reviewed in traditional Persian medicine (TPM) texts and then related with evidence from modern medicine by searching in databases, including PubMed, Scopus, Google Scholar, and IranMedex. RESULTS: From a traditional Persian scholar viewpoint, one of the most important causes of flatulence is an incorrect manner of eating; valuable advice to correct bad eating habits will be illustrated. In addition, traditional practitioners describe some herbs and vegetables as well as herbal compounds that are effective food additives to relieve flatulence. The anti-flatulent effect of most of these herbs has been experimentally verified using modern medicine. CONCLUSIONS: Attention to TPM can lead to the identification of new preventive and curative approaches to avoid and treat flatulence. In addition, Persian viewpoints from the medieval era regarding flatulence are historically important. PMID- 27275399 TI - Road Traffic Accident Victims' Experiences of Return to Normal Life: A Qualitative Study. AB - BACKGROUND: Road traffic accident (RTA) victims also suffer from different types of injuries and disabilities, which can affect their quality of life. They usually face with various physical, mental, and social problems. Most traffic accident victims had difficulty to return to normal life. OBJECTIVES: This study aimed to understand the experiences of return to normal life in RTA victims. PATIENTS AND METHODS: This qualitative study with content analysis approach was conducted on 18 Iranian patients with disability in the upper or lower limbs caused by traffic accidents, who had passed a time between 3 months till 2 years. A purposeful sampling method was applied until reaching data saturation. Data were collected using semi-structured interviews. Afterwards, the gathered data were analyzed through conventional content analysis. RESULTS: By analyzing 498 primary codes, four main categories, including supportive needs, adaptation to the new situation, seeking information, and transition from functional limitation, were extracted from traffic accident victims' experiences of reintegration to normal life. CONCLUSIONS: The results of this study may help policy-makers to take steps toward health promotion and recovery of RTA victims. Considering the results of this study, it is a need for further research to investigate RTAs victims' needs for reintegration to home and community. Access to training and supportive facilities like strong therapeutic, nursing and social support, and the possibility to participate in self-care activities is essential for reintegration to community in RTA victims. PMID- 27275400 TI - Association Between Outcomes and Demographic Factors in an Azeri Turkish Population With Cystic Fibrosis: A Cross-Sectional Study in Iran From 2001 Through 2014. AB - BACKGROUND: Outcomesforcystic fibrosis patients are improving rapidly. The demographic factors are notable variables inoutcomes, which can be evaluated and modified. OBJECTIVES: This study was designed to investigate the association between outcome and demographic factors in patients with cystic fibrosis. PATIENTS AND METHODS: This was a cross-sectional study and data were gathered for 331 patients using the census method, from March 2001 to September 2014 in Iran. Data was analyzed using logistic regression analysis, chi-square test, and independent sample t test using SPSS 18. Odds ratio with confidence intervals of 95% and P < 0.05 were considered significant. RESULTS: There were 85 (25.7%) deceased patients and 246 (74.3%) living patients at the time of the study. Of the 246 living CF patients, 202 (82.2%) were less than nine years of age, and 77 (90.6%) out of the 85 deceased CF patients had died younger than four years of age. There was a significant difference between outcome and location of residence. The risk of mortality was 50% less in urban patients than in rural patients (P = 0.03). The risk of mortality was approximately two times higher in patients with a positive family history than in those with a negative family history (P = 0.02). The proportion of mortality was approximately two times, or 94%, higher for those in a consanguineous marriage than for those in a non consanguineous marriage (P = 0.01). CONCLUSIONS: The results demonstrated that the mortality rate was higher in CF patients with a positive family history, a consanguineous marriage, and residence in a rural area. Therefore, demographic factors play an important role in the outcome of cystic fibrosis. Unfortunately, these parameters, which can be managed easily and with low cost, have been overlooked. PMID- 27275401 TI - Preemptive Analgesic Effects of Transcutaneous Electrical Nerve Stimulation (TENS) on Postoperative Pain: A Randomized, Double-Blind, Placebo-Controlled Trial. AB - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non pharmacological analgesic method used to control different types of pain. OBJECTIVES: The aim of this study was to evaluate the effects of preoperative TENS on post inguinal hernia repair pain. PATIENTS AND METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed on 66 male patients with unilateral inguinal hernias who were admitted to the Shahid Beheshti hospital in Kashan, Iran, from April to October 2014. Participants were selected using a convenience sampling method and were assigned to intervention (n = 33) and control (n = 33) groups using permuted-block randomization. Patients in the intervention group were treated with TENS 1 hour before surgery, while the placebo was administered to patients in the control group. All of the patients underwent inguinal hernia repair by the Lichtenstein method, and pain intensity was evaluated at 2, 4, 6, and 12 hours after surgery using a visual analogue scale. Additionally, the amounts of analgesic administered by pump were calculated and compared between the two groups. RESULTS: The mean estimated postoperative pain intensity was 6.21 +/- 1.63 in the intervention group and 5.45 +/- 1.82 in the control group (P = 0.08). In the intervention group pain intensity at 2 and 4 hours after surgery were 3.54 +/- 1.48 and 5.12 +/- 1.41 (P < 0.001), respectively. In the control group these values were 4.0+/-1.5 and 4.76 +/- 1.39 (P = 0.04), respectively. No significant differences were observed in mean pain intensities at 6 and 12 hours. CONCLUSIONS: TENS can reduce postoperative pain in the early hours after inguinal hernia repair surgery. PMID- 27275402 TI - The Effects of Group Play Therapy on Self-Concept Among 7 to 11 Year-Old Children Suffering From Thalassemia Major. AB - BACKGROUND: Children suffering from thalassemia have higher levels of depression and lower levels of self-concept. OBJECTIVES: The aim of this study was to determine if group play therapy could significantly increase self-concept among children with thalassemia major ages 7 to 11 years old in teaching hospitals of Golestan province, Iran, in 2012. PATIENTS AND METHODS: In this randomized, controlled clinical trial, 60 children with thalassemia major were randomly assigned to intervention (30 children) and control (30 children) groups. The intervention included eight 45 to 60 minute sessions during four weeks, during which the intervention group received group play therapy. The control group received no interventions. Self-concept was measured three times using the Piers Harris children's self-concept scale: before, immediately after, and a month after the intervention. RESULTS: For the intervention group, results showed that the mean self-concept score was significantly higher at the second point in time compared to the baseline (P < 0.001), going from 60.539 to 69.908. Likewise, comparing the first and third time points, the mean score significantly increased and reached 70.611 (P < 0.001). Furthermore, changes in the mean score from the second to the third time point, though non-significant (P = 0.509), followed the trend, going from 69.908 to 70.611. For the control group, comparing the first, second, and third time points did not result in any significant change in the mean score (P > 0.05). CONCLUSIONS: The results showed that group play therapy improves self-concept in children suffering from thalassemia major. PMID- 27275403 TI - Survey on Hypothermia and Hyperthermia in Poisoned Patients in a Unique Referral Hospital, Tehran, Iran. AB - BACKGROUND: Body temperature is a critical criterion of health. Drugs and a variety of poisons can affect body temperature in poisoned patients, causing hyperthermia and hyperpyrexia. OBJECTIVES: Our previous study's findings in patients poisoned with organophosphate led us to the goal of this study: obtaining the initial tympanic temperature in patients poisoned by a variety of toxins. MATERIALS AND METHODS: A cross-sectional study reviewed the records of poisoned patients who were admitted to the toxicological intensive care unit (TICU) at Loghman Hakim hospital poison center (LHHPC) from February 2014 to February 2015. The data collected included gender, age, type of poisoning, the season during which poisoning occurred, vital signs, initial tympanic temperature (first four hours), presence of seizures, white blood cell (WBC) count, creatinine phosphokinase (CPK), length of stay and patient outcome. We determined the mean (SD) for normally distributed continuous variables, the median and interquartile range for non-normally distributed continuous variables, and the absolute and relative frequency (%) for categorical variables. All were determined using SPSS version 16. RESULTS: Data were collected from 310 eligible patients. The mean patient age was 32.65 (with a standard deviation of 14.40). Of the patients in the study, 183 (59%) were male. Intentional poisoning in an attempted suicide was documented in 253 (81.6%) patients. The most prevalent poisoning agent was aluminum phosphate (18.70%), followed by methadone (10%) and opium (10%). Seventy percent of the patients (n = 217) were diagnosed and classified with fever or hyperthermia. A temperature >= 40 degrees C was detected in just three cases. The highest mean temperature was found in patients poisoned with amphetamine, organophosphate and tramadol. Patients with alcohol and phenobarbital poisoning were included in the sample, but these patients were not diagnosed with hypothermia. WBC >= 10,000 cells/mL and CPK >= 975 IU/L were recorded in 57.7% and 13.2% of subjects, respectively. CONCLUSIONS: Body temperature changes in human poisonings are a matter in need of special attention. A literature review did not reveal any controversy over hypothermia, but poisoning cases exhibit a variety of patterns of fever and hyperthermia. If there are no limits to the diagnosis of fever and hyperthermia, all cases with a poor prognosis which fail to respond to treatment could be categorized as drug induced hyperthermia. Therefore, a different approach is needed for poisoning cases. PMID- 27275404 TI - Heart Failing Jehovah Witness Patient Successfully Treated by Minimally-Invasive Left Ventricular Assist Device Implantation without any Blood Transfusions. PMID- 27275405 TI - Effects of Mands on Instructional Control: A Laboratory Simulation. AB - The effects of two types of mands on participants' adherence to instructions were examined across two groups using procedures based on Hackenberg and Joker (Journal of the Experimental Analysis of Behavior 62:367-383, 1994). Participants were presented with instructions describing a pattern of responding for producing points later exchanged for money and were exposed to choice trials in which a progressive-time (PT) and a fixed-time (FT) schedule were concurrently available. The instructions initially described how to optimize point production; however, the PT schedule was manipulated over the course of the experiment such that response patterns maximizing point production differed across conditions. All participants experienced the same experimental arrangement, and the two groups differed only in the form of the mand contained in the instructions presented to them. The instructions for the directive group contained the mand "you must..." (i.e., command) preceding the instructed response pattern, whereas the non directive group instructions contained the mand "you might consider..." (i.e., suggestion) preceding the instructed response pattern. Results indicated that instruction type influenced response patterns across changing contingencies. The directive group exhibited greater adherence to the instruction than the non directive group when instruction following was less profitable. Results are interpreted in terms of Skinner's analysis of verbal behavior, and implications for practical application are discussed. PMID- 27275406 TI - Multilevel D-loop PCR identification of hunting game. AB - The control region of mtDNA (D-loop) was used for hair samples of the five hunting game species identification: red deer (Cervus elaphus), roe deer (Capreolus capreolus), fallow deer (Dama dama), mouflon (Ovis aries musimon), and wild boar (Sus scrofa). For D-loop multilevel PCR detection scheme was applied in six primers (CE CVZV 1 = 5'-GATCACGAGCTTGATCACCA-3'; CE CVZV 2 = 5' AGGAGTGGGCGATTTTAGGT-3'; DD CVZV 3 = 5'-CGCGTGAAACCAACAACCCGC-3'; DD CVZV 4 = 5' CCGGGTCGGGGCCTTAGACG-3'; SSW CVZV 5 = 5'-ACACGTGCGTACACGCGCATA-3'; SSW CVZV 6 = 5'-GGTGCCTGCT T TCGTAGCACG-3') designed to identify unknown biological samples of the hunting game animals. The PCR reaction volume was 25 MUl at conditions 95 degrees C for 2 min, 94 degrees C for 30 s, 60 degrees C for 30 s, 72 degrees C for 30 s, 35 cycles, with last extension at 72 degrees C for 10 min. D-loop mtDNA amplicons of the game animals are characterized with specific PCR product sizes depending on species: red deer = 163 bp and 140 bp, fallow deer = 280 bp and 138 bp, roe deer = 303 bp, 280 bp, 160 bp and 138 bp, mouflon = 299 bp and 178 bp, wild boar = 137 bp and 229 bp. PMID- 27275407 TI - Association of polymorphism in cytochrome P450 2C9 with susceptibility to head and neck cancer and treatment outcome. AB - The present case-control study involving 750 cases and equal number of healthy controls investigates the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemotherapy or combination of radio-chemotherapy. The frequency of heterozygous or homozygous genotypes of CYP2C9*2 & CYP2C9*3, which leads to the poor metabolizer (PM) genotype was significantly higher in HNSCC cases when compared to the healthy controls resulting in significantly increased risk in the cases. Tobacco use in the form of tobacco smoking or tobacco chewing was found to increase the risk several fold in cases when compared to the non tobacco users. Likewise, alcohol intake in cases with variant genotypes of CYP2C9*2 or CYP2C9*3 also significantly increased the HNSCC risk in cases when compared to non-alcohol users. Further, majority of the cases carrying variant alleles of both CYP2C9*2 or CYP2C9*3 were found to respond poorly to the chemotherapy or combination of radio-chemotherapy. The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome. PMID- 27275408 TI - Cloning and expression of dnaK gene from Bacillus pumilus of hot water spring origin. AB - A set of thermotolerant strains isolated from hot springs of Manikaran and Bakreshwar (India) were selected with an aim to isolate dnak gene which encodes DnaK protein. The gene dnaK along with its flanking region was successfully amplified from 5 different strains (4 from Bakreshwar and one from Manikaran). Restriction fragment length polymorphism (RFLP) revealed that amplicons were almost identical in sequence. The dnak gene from one representative, Bacillus pumilus strain B3 isolated from Bakreshwar hot springs was successfully cloned and sequenced. The dnaK gene was flanked by gene grpE on one side. The dnaK gene was 1842 bp in length encoding a polypeptide of 613 amino acid residues. Calculated molecular weight and pI of the protein were 66,128.36 Da and 4.72 respectively. The deduced amino acid sequence of this gene shared high sequence homology with other DnaK proteins and its homologue Hsp 70 from other microorganisms, but possessed 36 substitutions and two insertions, as compared to DnaK protein of Bacillus subtilis. The dnaK gene of B. pumilus was successfully expressed in Escherichia coli BL 21 (DE3) using pET expression systems. Heterologous expression of dnaK of B. pumilus in E. coli BL 21 (DE3) allowed for the growth of E. coli up to 50 degrees C and survival up to 60 degrees C for 16 h, suggesting that dnak from B. pumilus imparts tolerance to host cells under high temperature. This novel gene can be an important component for possible utilization in abiotic stress management of plants. PMID- 27275409 TI - Special Issue - From Biobanks to the Clinic. PMID- 27275410 TI - Rare disease research: Breaking the privacy barrier. AB - Due to the few patients affected, rare disease research has to count on international registries to exist in order to produce significant research outputs. Data sharing of registries is therefore a unique resource to allow rare disease research to flourish and any lost data will jeopardize the quality of an already extremely difficult research. The rules usually applied to research such as the right to withdraw or the need for specific consent for every use of data can be detrimental in order to get effective results. Privacy rights regulated through traditional informed consent mechanisms have been regarded as a major barrier in order to effectively share data worldwide. Some authors argue that this barrier hampers results that could be beneficial to the patients so that another right will be overstated: the right to quality healthcare. We argue in this paper that privacy has been often interpreted just one-sided as the right to secrecy but it can entail another meaning: the right to manage one's own private sphere. Managing it pertains, not only to the right to deny access, but also to the right to grant access. At the same time research on patient participation and transparency shows that new forms of IT-based informed consent can provide a good balance between the right of individuals to be in control of their data and the opportunity for science to pursue international research. PMID- 27275411 TI - Biobanking and translation of human genetics and genomics for infectious diseases. AB - Biobanks are invaluable resources in genomic research of both the infectious diseases and their hosts. This article examines the role of biobanks in basic research of infectious disease genomics, as well as the relevance and applicability of biobanks in the translation of impending knowledge and the clinical uptake of knowledge of infectious diseases. Our research identifies potential fields of interaction between infectious disease genomics and biobanks, in line with global trends in the integration of genome-based knowledge into clinical practice. It also examines various networks and biobanks that specialize in infectious diseases (including HIV, HPV and Chlamydia trachomatis), and provides examples of successful research and clinical uptake stemming from these biobanks. Finally, it outlines key issues with respect to data privacy in infectious disease genomics, as well as the utility of adequately designed and maintained electronic health records. We maintain that the public should be able to easily access a clear and detailed outline of regulations and procedures for sample and data utilization by academic or commercial investigators, and also should be able to understand the precise roles of relevant governing bodies. This would ultimately facilitate uptake by researchers and clinics. As a result of the efforts and resources invested by several networks and consortia, there is an increasing awareness of the prospective uses of biobanks in advancing infectious disease genomic research, diagnostics and their clinical management. PMID- 27275412 TI - P(3)G - 10 years of toolbuilding: From the population biobank to the clinic. AB - Over the past ten years, the Public Population Project in Genomics and Society ("P(3)G") has grown as a consortium. It has expanded its range of services and resources to adapt to the ever-evolving needs of the research community. From its outset - when P(3)G first tackled the building of biobanks as resources as well as data cataloguing and harmonization for data integration - to its new mission and vision, it has continually developed the tools for the conceptualization and design of population biobanks from their inception to their use to their closure. In so doing, P(3)G has become key in fostering research infrastructures to facilitate transition to the clinic. The consortium has become a crucial stakeholder in the international scientific, ethical, legal, and social research communities. PMID- 27275413 TI - Comprehensive and computational analysis of genes in human umbilical vein endothelial cells responsive to X-irradiation. AB - Radiation exposure such as A-bomb or radiation therapy is considered a major health-risk factor for cardiovascular disease. In order to understand the molecular mechanisms underlying the inflammatory reaction frequently encountered in the vascular system after exposure to ionizing radiation, we carried out a global scale microarray and computational gene expression analyses on human umbilical endothelial cells (HUVECs) exposed to X-ray (2.5 Gy). The gene ontology analysis revealed that the down-regulated genes were associated with cell cycle regulation, whereas the up-regulated genes were associated with inflammatory responses, in particular, the type 1 interferon response. The computational analysis using ingenuity pathway analysis also identified a gene network containing the interferon response factor 7 (IRF7) and its transcriptional targets such as interferon-induced transcripts (IFITs) and Mx1, which have been known to be associated with inflammation in endothelial cells. The up-regulated genes and the gene network identified here may explain the inflammatory response induced by X-irradiation. These findings uncover part of the molecular basis of the mechanism(s) of the inflammatory disorder in response to X-irradiation in HUVECs. The dataset is publicly available at the Gene Expression Omnibus (GEO) repository (http://www.ncbi.nlm.nih.gov/geo/) with accession number GSE76484. PMID- 27275414 TI - Combined sequencing of mRNA and DNA from human embryonic stem cells. AB - Combined transcriptome and whole genome sequencing of the same ultra-low input sample down to single cells is a rapidly evolving approach for the analysis of rare cells. Besides stem cells, rare cells originating from tissues like tumor or biopsies, circulating tumor cells and cells from early embryonic development are under investigation. Herein we describe a universal method applicable for the analysis of minute amounts of sample material (150 to 200 cells) derived from sub colony structures from human embryonic stem cells. The protocol comprises the combined isolation and separate amplification of poly(A) mRNA and whole genome DNA followed by next generation sequencing. Here we present a detailed description of the method developed and an overview of the results obtained for RNA and whole genome sequencing of human embryonic stem cells, sequencing data is available in the Gene Expression Omnibus (GEO) database under accession number GSE69471. PMID- 27275415 TI - Sustained-release genistein from nanostructured lipid carrier suppresses human lens epithelial cell growth. AB - AIM: To design and investigate the efficacy of a modified nanostructured lipid carrier loaded with genistein (Gen-NLC) to inhibit human lens epithelial cells (HLECs) proliferation. METHODS: Gen-NLC was made by melt emulsification method. The morphology, particle size (PS), zeta potentials (ZP), encapsulation efficiency (EE) and in vitro release were characterized. The inhibition effect of nanostructured lipid carrier (NLC), genistein (Gen) and Gen-NLC on HLECs proliferation was evaluated by cell counting kit-8 (CCK-8) assay, gene and protein expression of the proliferation marker Ki67 were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence analyses. RESULTS: The mean PS of Gen-NLC was 80.12+/-1.55 nm with a mean polydispersity index of 0.11+/-0.02. The mean ZP was -7.14+/-0.38 mV and the EE of Gen in the nanoparticles was 92.3%+/-0.73%. Transmission electron microscopy showed that Gen NLC displayed spherical-shaped particles covered by an outer-layer structure. In vitro release experiments demonstrated a prolonged drug release for 72h. The CCK 8 assay results showed the NLC had no inhibitory effect on HLECs and Gen-NLC displayed a much more prominent inhibitory effect on cellular growth compared to Gen of the same concentration. The mRNA and protein expression of Ki67 in LECs decreased significantly in Gen-NLC group. CONCLUSION: Sustained drug release by Gen-NLCs may impede HLEC growth. PMID- 27275416 TI - Use of high-throughput targeted exome sequencing in genetic diagnosis of Chinese family with congenital cataract. AB - AIM: To identify disease-causing mutation in a congenital cataract family using enrichment of targeted genes combined with next-generation sequencing. METHODS: A total of 371 known genes related to inherited eye diseases of the proband was selected and captured, followed by high-throughput sequencing. The sequencing data were analyzed by established bioinformatics pipeline. Validation was performed by Sanger sequencing. RESULTS: A recurrent heterozygous non-synonymous mutation c.130G>A (p.V44M) in the GJA3 gene was identified in the proband. The result was confirmed by Sanger sequencing. The mutation showed co-segregation with the disease phenotype in the family but was not detected in unaffected controls. CONCLUSION: Targeted exome sequencing is a rapid, high-throughput and cost-efficient method for screening known genes and could be applied to the routine gene diagnosis of congenital cataract. PMID- 27275417 TI - Human melanopsin-AAV2/8 transfection to retina transiently restores visual function in rd1 mice. AB - AIM: To explore whether ectopic expression of human melanopsin can effectively and safely restore visual function in rd1 mice. METHODS: Hematoxylin-eosin staining of retinal sections from rd1 mice was used to detect the thickness of the outer nuclear layer to determine the timing of surgery. We constructed a human melanopsin-AAV2/8 viral vector and injected it into the subretinal space of rd1 mice. The Phoenix Micron IV system was used to exclude the aborted injections, and immunohistochemistry was used to validate the ectopic expression of human melanopsin. Furthermore, visual electrophysiology and behavioral tests were used to detect visual function 30 and 45d after the injection. The structure of the retina was compared between the human melanopsin-injected group and phosphate buffer saline (PBS)-injected group. RESULTS: Retinas of rd1 mice lost almost all of their photoreceptors on postnatal day 28 (P28). We therefore injected the human melanopsin-adeno-associated virus (AAV) 2/8 viral vector into P30 rd1 mice. After excluding aborted injections, we used immunohistochemistry of the whole mount retina to confirm the ectopic expression of human melanopsin by co-expression of human melanopsin and YFP that was carried by a viral vector. At 30d post-injection, visual electrophysiology and the behavioral test significantly improved. However, restoration of vision disappeared 45d after human melanopsin injection. Notably, human melanopsin-injected mice did not show any structural differences in their retinas compared with PBS-injected mice. CONCLUSION: Ectopic expression of human melanopsin effectively and safely restores visual function in rd1 mice. PMID- 27275418 TI - In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype. AB - AIM: To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. METHODS: A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. RESULTS: By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A) of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. CONCLUSION: The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment. PMID- 27275419 TI - Anti-proliferative effect of olmesartan on Tenon's capsule fibroblasts. AB - AIM: To evaluate the inhibitive effect of olmesartan to fibroblast proliferation and the anti-scarring effect in Tenon's capsule, both in vitro and in vivo. METHODS: Human primary Tenon's capsule fibroblasts were cultured in vitro, treated with up titrating concentrations of olmesartan. The rate of inhibition was tested with methyl thiazol tetrazolium (MTT) method. Real-time PCR was performed to analyze changes in mRNA expressions of the fibrosis-related factors: matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase (TIMP 1,2) and proliferating cell nuclear antigen (PCNA). Thirty rabbits were divided into 5 groups (3, 7, 14, 21, and 28d). A rabbit conjunctiva flap model was created in each eye. Olmesartan solution was injected subconjunctivally and then evaluated its anti-proliferation and anti-fibrosis effects through the histological morphology and immunohistochemistry of MMP-2 and PCNA in each group. Only the 7d group was treated with Masson's trichrome to compare the neovascularization in the subconjunctiva area. RESULTS: In vitro, cultured Tenon's capsule human fibroblasts showed a dose dependent inhibition by olmesartan in MTT. Olmesartan reduced mRNA expressions of MMP-2 and PCNA but increased mRNA expressions of TIMP-1 and TIMP-2. In vivo, the rabbit eyes treated with olmesartan at 3(rd), 7(th), 14(th) and 21(st) days demonstrated a significant reduced expressions of MMP-2 and PCNA compared with control eye, no significant difference observed in 28(th) day group. The cellular proliferation and neovascularization was suppressed by olmesartan in Masson's trichrome observation. CONCLUSION: By inhibiting fibroblasts in vitro and in vivo, olmesartan prevents the proliferation and activity of fibroblasts in scar tissue formation, which might benefit glaucoma filtering surgery. PMID- 27275421 TI - Real-time polymerase chain reaction for the diagnosis of necrotizing herpes stromal keratitis. AB - AIM: To design, optimize and validate a rapid, internally controlled real-time polymerase chain reaction (RT-PCR) test for herpes simplex virus (HSV) in the diagnosis of necrotizing herpes stromal keratitis. METHODS: Tears alone or together with corneal epithelium scrapings from 30 patients (30 eyes) suspected of necrotizing herpes stromal keratitis were tested for HSV DNA by RT-PCR. The samples were collected during the first visit and then on the subsequent 7, 14, 28, 42, and 56d. The symptoms of the patients were scored before treatment to determine the correlation between HSV concentration in the corneal epithelium scrapings and clinical scores. RESULTS: The positive rate (46.4%) in the corneal epithelium group before the therapy was significantly higher than that (13.3%) in the tears group (P=0.006). There were 13 positive HSV patients before the therapy, the concentration of HSV DNA in corneal epithelium scrapings group was significantly higher than that in the tears group (paired t-test, P=0.0397). Multilevel mixed-effects model analysis showed that the difference between the corneal epithelium scrapings group and the tears group was statistically significant (P=0.0049). The Spearman rank correlation analysis indicated a positive correlation between the HSV concentration in the corneal epithelium scrapings and clinical scores before the treatment (r=0.844, P<0.0001). CONCLUSION: RT-PCR appears to be a powerful molecular tool for the diagnosis of necrotizing herpes stromal keratitis. PMID- 27275420 TI - Effect of sodium tungstate on visual evoked potentials in diabetic rats. AB - AIM: To evaluate the effect of sodium tungstate on visual evoked potentials (VEPs) in diabetic rats. METHODS: Wistar rats were randomly divided into three groups as normal control, diabetic control and diabetic rats treated with sodium tungstate. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg). Sodium tungstate [40 mg/(kg.d)] was administered for 12wk and then VEPs were recorded. Additionally, thiobarbituric acid reactive substance (TBARS) levels were measured in brain tissues. RESULTS: The latencies of P1, N1, P2, N2 and P3 waves were significantly prolonged in diabetic rats compared with control group. Diabetes mellitus caused an increase in the lipid peroxidation process that was accompanied by changes in VEPs. However, prolonged latencies of VEPs for all components returned to control levels in sodium tungstate-treated group. The treatment of sodium tungstate significantly decreased brain TBARS levels and depleted the prolonged latencies of VEP components compared with diabetic control group. CONCLUSION: Sodium tungstate shows protective effects on visual pathway in diabetic rats, and it can be worthy of further study for potential use. PMID- 27275422 TI - Comparison of phacotrabeculectomy and sequential surgery in the treatment of chronic angle-closure glaucoma coexisted with cataract. AB - AIM: To compare the safety and effectiveness of phacotrabeculectomy versus sequential surgery in chronic angle-closure glaucoma (CACG) with coexisting cataract. METHODS: One hundred and sixty-two CACG patients (162 eyes) were retrospectively analyzed. Of them, 87 patients (87 eyes) in group A had underwent phacotrabeculectomy with intraocular lens (IOL) implantation, and 75 patients (75 eyes) in group B had underwent sequential surgery with IOL implanted. Best corrected visual acuity (BCVA), intraocular pressure (IOP), complications and anterior chamber angle (ACA) were measured. RESULTS: Demographic characteristics of the two groups were similar. A mean follow-up period was 15+/-6mo (range 13 to 24mo), a mean IOP of 16.61+/-6.43 mm Hg in group A and 15.80+/-5.35 mm Hg in group B (P=0.84) at the last follow up. The Kaplan-Meier analysis revealed that the cumulative probability of success in both groups was similar (P=0.61). Anterior uveitis and hypotony were the most common complications in group A, whereas group B experienced shallow anterior chamber with trabeculectomy. With the exception of anterior uveitis, no complications occurred to 11 trabeculectomized eyes. All postoperative measurements of anterior chamber showed statistically significant differences in each group according to the preoperative data (P<0.05). However, fewer changes occurred in group B than in group A. CONCLUSION: Phacotrabeculectomy and sequential surgery exhibit similar IOP reduction, visual recovery, and complications when treating CACG patients with cataract. However, for a wider ACA, phacotrabeculectomy has demonstrated higher effectiveness than sequential surgery. PMID- 27275423 TI - Efficacy of combined cataract extraction and endoscopic cyclophotocoagulation for the reduction of intraocular pressure and medication burden. AB - AIM: To report on the efficacy of combined endoscopic cyclophotocoagulation (ECP) and phacoemulsification cataract extraction (PCE) with intraocular lens placement for reduction of intraocular pressure (IOP) and medication burden in glaucoma. METHODS: A retrospective case review of 91 eyes (73 patients) with glaucoma and cataract that underwent combined PCE/ECP surgery was performed. Baseline demographic and ocular characteristics were recorded, as well as intraocular pressure, number of glaucoma medications, and visual acuity postoperatively with 12-month follow-up. Treatment failure was defined as less than 20% reduction in IOP from baseline on two consecutive visits (at 1, 3, 6, or 12mo postoperatively), IOP >=21 mm Hg or <=5 mm Hg on two consecutive visits, or additional glaucoma surgery performed within 12mo after PCE/ECP. RESULTS: Overall, mean medicated IOP was reduced from 16.65 mm Hg at baseline to 13.38 mm Hg at 12mo (P<0.0001). Mean number of glaucoma medications was reduced from 1.88 medications at baseline to 1.48 medications at 12mo (P=0.0003). At 3mo postoperatively, the success rate was 73.6% (95%CI: 63.3, 81.5), 57.1% at 6mo (95% CI: 46.3, 66.6), and 49.7% at 12mo (95%CI: 38.9, 59.6). Patient demographic characteristics were not associated with treatment success. The only ocular characteristic associated with treatment success was a higher baseline IOP. CONCLUSION: Combined PCE/ECP surgery is an effective surgical option for the reduction of IOP and medication burden in glaucoma patients. Patients with higher baseline IOP levels are most likely to benefit from this procedure. PMID- 27275424 TI - The refractive outcome of Toric Lentis Mplus implant in cataract surgery. AB - AIM: To evaluate the refractive outcome of Toric Lentis Mplus intraocular lens (IOL) implant. METHODS: This is a retrospective case series. Consecutive patients with corneal astigmatism of at least 1.5 D had Toric Lentis Mplus IOL implant during cataract surgery. The exclusion criteria included irregular astigmatism on corneal topography, large scotopic pupil diameter (>6 mm), poor visual potential and significant ocular comorbidity. Postoperative manifest refraction, uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BCVA), uncorrected intermediate visual acuity (UIVA) at 3/4 m and uncorrected near visual acuity (UNVA) were obtained. RESULTS: There were 70 eyes from 49 patients in this study. Patients were refracted at a median of 8.9wk (range 4.0 to 15.5) from the operation date. Sixty-five percent of eyes had 6/7.5 (0.10 logMAR) or better, and 99% 6/12 (0.30 logMAR) or better postoperative UDVA. Eighty-nine percent could read Jaeger (J) 3 (0.28 logMAR) and 95% J5 (0.37 logMAR) at 40 cm. The median magnitude of astigmatism decreased from 1.91 D to 0.49 D (Wilcoxon, P<0.001) after the operation. The range of the cylindrical error was reduced from 1.5-3.95 D (keratometric) preoperatively to 0.00-1.46 D (subjective refraction transposed to corneal plane) postoperatively. CONCLUSION: Toric Lentis Mplus IOL has good predictability in reducing preexisting corneal astigmatism. PMID- 27275425 TI - Comparison of two different methods of preoperative marking for toric intraocular lens implantation: bubble marker versus pendulum marker. AB - AIM: To compare the accuracy of two different methods of preoperative marking for toric intraocular lens (IOL) implantation, bubble marker versus pendulum marker, as a means of establishing the reference point for the final alignment of the toric IOL to achieve an outcome as close as possible to emmetropia. METHODS: Toric IOLs were implanted in 180 eyes of 110 patients. One group (55 patients) had preoperative marking of both eyes done with bubble marker (ASICO AE-2791TBL) and the other group (55 patients) with pendulum marker (Rumex((r))3-193). Reference marks were placed at 3-, 6-, and 9-o'clock positions on the limbus. Slit-lamp photographs were analyzed using Adobe Photoshop (version 7.0). Amount of alignment error (in degrees) induced in each group was measured. RESULTS: Mean absolute rotation error in the preoperative marking in the horizontal axis was 2.42+/-1.71 in the bubble marker group and 2.83+/-2.31in the pendulum marker group (P=0.501). Sixty percent of the pendulum group and 70% of the bubble group had rotation error <=3 (P=0.589), and 90% eyes of the pendulum group and 96.7% of the bubble group had rotation error <=5 (P=0.612). CONCLUSION: Both preoperative marking techniques result in approximately 3 of alignment error. Both marking techniques are simple, predictable, reproducible and easy to perform. PMID- 27275426 TI - The association analysis polymorphism of CDKAL1 and diabetic retinopathy in Chinese Han population. AB - AIM: To identify the contribution of CDKAL1 to the development of diabetic retinopathy (DR) in Chinese population. METHODS: A case-control study was performed to investigate the genetic association between DR and polymorphic variants of CDKAL1 in Chinese Han population with type 2 diabetes mellitus (T2DM). A well-defined population with T2DM, consisting of 475 controls and 105 DR patients, was recruited. All subjects were genotyped for the genetic variant (rs10946398) of CDKAL1. Genotyping was performed by iPLEX technology. The association between rs10946398 and T2DM was assessed by univariate and multivariate logistic regression (MLR) analysis. RESULTS: There were significant differences in C allele frequencies of rs10946398 (CDKAL1) between control and DR groups (45.06% versus 55.00%, P<0.05). The rs10946398 of CDKAL1 was found to be associated with the increased risk of DR among patients with diabetes. CONCLUSION: Our findings suggest that rs10946398 of CDKAL1 is independently associated with DR in a Chinese Han population. PMID- 27275427 TI - Infrared autofluorescence, short-wave autofluorescence and spectral-domain optical coherence tomography of optic disk melanocytomas. AB - AIM: To investigate the findings of infrared fundus autofluorescence (IR-AF) and spectral-domain optical coherence tomography (SD-OCT) in eyes with optic disc melanocytoma (ODM). METHODS: IR-AF findings and those of other ophthalmologic imaging examinations, including short-wave autofluorescence (SW-AF), fluorescein angiography (FA), fundus color photography, and SD-OCT of 8 eyes of 8 consecutive cases with ODM were assessed. RESULTS: The ODMs in all cases (100%) presented similar IR-AF, SW-AF, and FA findings. On IR-AF images, ODMs showed outstanding hyper-AF with well-defined outline. On SW-AF images, the area of ODMs presented as hypo-AF. FA images revealed the leaking retinal telangiectasia on the surface of the ODMs. On SD-OCT images in 8 cases (100%), the ODMs were sloped with highly reflective surface, which were disorganized retina and optic nerve layers. In 7 cases (87.5%), peripapillary choroids were involved. The melanocytomas of 8 cases (100%) presented as optically empty spaces. Vitreous seeds were found in one case (12.5%). CONCLUSION: IR-AF imaging may provide a new modality to evaluate the pathologic features of ODMs, and together with SW-AF imaging, offers a new tool to study biological characteristics associated with ODMs. SD-OCT is a valuable tool in delimitating the tumor extension and providing morphological information about the adjacent retinal tissue. PMID- 27275428 TI - Axial length in unilateral idiopathic central serous chorioretinopathy. AB - AIM: To evaluate the axial length (AXL) in unilateral idiopathic central serous chorioretinopathy (CSC). METHODS: This retrospective case-control study was comprised of a consecutive case series of 35 patients with acute unilateral idiopathic CSC, and age- and sex-matched 50 control eyes. AXL of both eyes of unilateral CSC patients and the control eyes were investigated. AXL was measured by ultrasonic biometry, and the adjusted AXL was calculated for CSC eyes as measured AXL plus differences of foveal thickness between CSC and normal fellow eyes in millimeters. The main outcome measures were comparison of AXL between CSC, fellow and control eyes. RESULTS: The mean age of 35 CSC patients was 45.5y, and 31 males were included. The adjusted AXL of CSC eyes was 23.52 mm, and the AXL of fellow eyes was 23.46 mm, and of control eyes 23.94 mm. The AXL of both CSC and fellow eyes were significantly shorter than control eyes (CSC vs control, P=0.044; fellow vs control, P=0.026). There was no statistically significant difference in AXL between CSC and fellow eyes. CONCLUSION: In unilateral idiopathic CSC, the AXL of CSC and fellow eyes are shorter than that of control eyes. Short AXL may be related with choroidal circulation abnormality in CSC. PMID- 27275429 TI - Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus. AB - AIM: To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients. METHODS: Aqueous humor and plasma samples from 26 patients with DR (in nonproliferative and proliferative stages) and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme linked immunosorbent assay (ELISA). RESULTS: Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy (PDR) [18.57+/-2.67 pg/mL (range 15.20-23.06) vs 13.63+/-2.71 pg/mL (range 10.20 20.20), P=0.0001], but not in those with nonproliferative retinopathy (NPDR) [13.79+/-2.56 pg/mL (range 9.80-20.10) vs 13.63+/-2.71 pg/mL (range 10.20-20.20), P=0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [5.37+/-1.74 pg/mL (range 2.85-8.65) vs 6.11+/-1.90 pg/mL (range 3.13-9.41), P=0.293], or between control and DR groups [NPDR 6.11+/ 1.90 pg/mL (range 3.13-9.41) vs control 6.15+/-1.91 pg/mL (range 2.18-9.86); PDR (5.37+/-1.74 pg/mL (range 2.85-8.65) vs control 6.15+/-1.91 pg/mL (range 2.18 9.86), P=0.808, P=0.264]. CONCLUSION: Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity. PMID- 27275430 TI - Choroidal thickness measurements with optical coherence tomography in branch retinal vein occlusion. AB - AIM: To evaluate central macular thickness (CMT) and mean choroidal thickness (MCT) in eyes with branch retinal vein occlusion (BRVO), before and after ranibizumab treatment using spectral domain-optical coherence tomography (SD OCT). METHODS: Forty-two patients with unilateral BRVO and macular edema were included in this study. There were 25 men and 17 women. Using SD-OCT, choroidal thickness was measured at 500 um intervals up to 1500 um temporal and nasal to the fovea. MCT was calculated based on the average of the 7 locations. All the eyes with BRVO were treated with intravitreal ranibizumab (0.5 mg/0.05 mL). Comparisons between the BRVO and fellow eyes were analyzed using Mann-Whitney U test. Pre-injection and post-injection measurements were analyzed using Wilcoxon test and repeated measure analysis. RESULTS: At baseline, there was a significant difference between the BRVO and fellow eyes in MCT [BRVO eyes 245 (165-330) um, fellow eyes 229 (157-327) um] and CMT [BRVO eyes 463 (266-899) um, fellow eyes 235 (148-378) um (P=0.041, 0.0001, respectively)]. Following treatment, CMT [295 (141-558) um] and MCT [229 (157-329) um] decreased significantly compared to the baseline measurements (P=0.001, 0.006, respectively). Also BCVA (logMAR) improved significantly (P=0.0001) in the BRVO eyes following treatment. After treatment CMT [BRVO eyes 295 (141-558) um, fellow eyes 234 (157-351) um] and MCT [BRVO eyes 229 (157-329) um, fellow eyes 233 (162-286) um] values did not reveal any significant difference in BRVO eyes and fellow eyes (P=0.051, 0.824, respectively). CONCLUSION: In eyes with BRVO, CMT and MCT values are greater than the fellow eyes, and decrease significantly following ranibizumab injection. PMID- 27275431 TI - Clinical features and in vivo confocal microscopy assessment in 12 patients with ocular cicatricial pemphigoid. AB - AIM: To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy (IVCM) in patients with ocular cicatricial pemphigoid (OCP). METHODS: A descriptive, uncontrolled case series study. Patients diagnosed with OCP were examined by clinical history, slit-lamp biomicroscopy features and IVCM images. The results of direct immunofluorescence (DIF) biopsies and indirect immunofluorescence (IIF) were also recorded. Local and systemic immunosuppressive therapy were administered and adjusted according to response. RESULTS: A total of 12 consecutive OCP patients (7 male, 5 female; mean age 60.42+/-10.39y) were recruited. All patients exhibited bilateral progressive conjunctival scarring and recurrent chronic conjunctivitis was the most frequent clinical pattern. The mean duration of symptoms prior to diagnosis of OCP was 2.95+/-2.85y (range: 5mo to 10y). The Foster classification varied from stage I to IV and 20 eyes (83%) were within or greater than Foster stage III on presentation. Two of the 12 patients (17%) demonstrated positive DIF; 3 of the 12 (25%) patients reported positive IIF. The mean duration of the follow-up period was 20.17+/-11.88mo (range: 6 to 48mo). IVCM showed variable degrees of abnormality in the conjuctiva-cornea and conjuctival scarring was detected in all the involved eyes. Corneal stromal cell activation and dendritic cell infiltration presented as ocular surface inflammation, ocular surface keratinization along with the destroyed Vogt palisades was noted in eyes with potential limbal stem cell deficiency. After treatment, remission of ocular surface inflammation was achieved in all the patients, 18 eyes (75%) remained stable, 6 eyes (25%) had recurrent conjunctivitis and cicatrization in 2 eyes (8%) was progressing. CONCLUSION: As an autoimmune disease, OCP manifests as variable degrees of clinical and laboratory abnormalities with both local and systemic immunosuppressive treatment playing important roles in disease therapy. IVCM can be as a valuable non-invasive technique to assess ocular surface changes in a cellular level with a potential value for providing diagnostic evidence and monitoring therapeutic effects during follow-up. PMID- 27275432 TI - Ocular trauma treated with pars plana vitrectomy: early outcome report. AB - AIM: To evaluate demographic variables and visual outcomes, among patients with ocular injuries involving the posterior segment, managed with pars plana vitrectomy. METHODS: The records of patients were studied retrospectively from March to September 2010, to determine the age, gender, place of occurrence of trauma, visual acuity, anatomical site, nature of injury, wound length, the presence of an afferent pupillary defect, and the timing of vitrectomy. The Ocular Trauma Score was measured. The minimum follow-up from presentation was 6mo. RESULTS: Ninety patients (77 males, 13 females), with a mean age of 32.7+/ 15.8y were included over the 6-month period. The majority of cases occurred in the workplace (47 patients), followed by home (14 patients). The mean visual acuity (logMAR) of patients significantly improved from 2.36+/-0.72 preoperatively to 1.50+/-1.14 postoperatively. Twenty-three patients had preoperative vision better than 2.0 logMAR, the postoperative visual acuity was significantly better among these patients than patients with worse than 2.0 logMAR (P<0.001). Visual improvement between groups with early vitrectomy (<7d) and delayed vitrectomy (>7d) was not significantly different (P=0.66). Postoperative visual acuity was not significantly different between patients with injury in Zone I and II (P=0.64), but patients with injury in Zone III had significantly poorer visual acuity (P=0.02). Patients with relative afferent pupillary defect had significantly poorer postoperative visual acuity (P=0.02). Preoperative visual acuity, the difference of preoperative and postoperative visual acuity, and postoperative visual acuity were significantly different between groups with different ocular trauma scores (P<0.001). CONCLUSION: Trauma is more likely to occur in men under 40y of age and in the workplace. The favorable final visual outcome is associated with the absence of afferent pupillary defect, ocular trauma score and presenting visual acuity as well as the zone of injury, and not associated with the timing of vitrectomy. PMID- 27275433 TI - An overlooked effect of systemic anticholinergics: alteration on accommodation amplitude. AB - AIM: To investigate the effect of oral solifenacin succinate, tolterodine-L tartarate and oxybutinin hydrochloride (HCl) on accommodation amplitude. METHODS: Female overactive bladder syndrome (OAB) patients who were planned to use oral anticholinergics, patients that uses solifenacin succinate 5 mg (Group I, n=25), tolterodine-L-tartarate 4 mg (Group II, n=25), and oxybutinin HCl 5 mg b.i.d (Group III, n=25) and age matched healthy female subjects (Group IV, n=25) were recruited and complete ophthalmological examination and accommodation amplitude assessment were done at baseline and 4wk after initiation of treatment. RESULTS: The mean age of 100 consecutive female subjects was 51.6+/-5.7 (40-60)y and there were no statistically significant difference with regard to the mean age (P=0.107) and baseline accommodation amplitude (P=0.148) between study groups. All treatment groups showed a significant decrease in accommodation amplitude following a 4-week course of anticholinergic treatment (P=0.008 in Group I, P=0.002 in Group II, P=0.001 in Group III), but there was no statistically significant difference in Group IV (P=0.065). CONCLUSION: A 4-week course of oral anticholinergic treatment have statistically significant effect on accommodation amplitude. Clinicians should avoid both overestimating this result, as this would unnecessarily restrict therapeutic possibilities, and also underestimating it which may lead to drug intolerance. PMID- 27275434 TI - Binocular vision and abnormal head posture in children when watching television. AB - AIM: To determine the association between the binocular vision and an abnormal head posture (AHP) when watching television (TV) in children 7-14y of age. METHODS: Fifty normal children in the normal group and 52 children with an AHP when watching TV in the AHP group were tested for spherical equivalents, far and near fusional convergence (FC) and fusional divergence (FD) amplitudes, near point of convergence, far and near heterophoria, accommodative convergence/ accommodation ratio and stereoacuity. The values of these tests were compared between the two groups. The independent t test was applied at a confidence level of 95%. RESULTS: The far and near FC amplitudes and far FD amplitudes were lower in the AHP group (the far FC amplitudes: break point 13.6+/-5.4(Delta), recovery point 8.7+/-5.4(Delta). The near FC amplitudes: break point 14.5+/-7.3(Delta), recovery point 10.3+/-5.1(Delta). The far FD amplitudes: break point 3.9+/ 2.7(Delta), recovery point 2.6+/-2.3(Delta)) compared with those in the normal group (the far FC amplitudes: break point 19.1+/-6.2(Delta), recovery point 12.4+/-4.5(Delta). The near FC amplitudes: break point 22.3+/-8.0(Delta), recovery point 16.1+/-5.7(Delta). The far FD amplitudes: break point 7.0+/ 2.1(Delta), recovery point 4.6+/-1.9(Delta)). Other tests presented no statistically significant differences. CONCLUSION: An association between the reduced FC and FD amplitudes and the AHP in children when watching TV is proposed in the study. This kind of AHP is considered to be an anomalous manifestation which appears in a part of puerile patients of fusional vergence dysfunction. PMID- 27275435 TI - Long-term assessment of prostaglandin analogs and timolol fixed combinations vs prostaglandin analogs monotherapy. AB - AIM: To draw a Meta-analysis over the comparison of the intraocular pressure (IOP)-lowering efficacy and safety between the commonly used fixed-combinations of prostaglandin analogs and 0.5% timolol with prostaglandin analogs (PGAs) monotherapy. METHODS: After searching the published reports from MEDLINE, EMBASE, the Cochrane Library, all randomized controlled clinical trials (RCTs) comparing the fixed combination of PGAs/timolol therapy (FCs) and PGAs monotherapy with treatment duration at least 6mo were included. The efficacy outcomes were mean diurnal IOP, percentage of participants whose IOP were lower than 18 mm Hg, incidence of visual field change, while the safety outcomes included corneal side effects, hyperemia and eye irritation. The analysis was carried out in RevMan version 5.3 software. RESULTS: After six-month medical intervention, the mean diurnal IOP of FCs was lower than PGAs (MD -1.14, 95% CI -1.82 to -0.46, P=0.001); the percentage of target IOP achieving between FCs and PGAs showed no significant difference (RR 1.18, 95% CI 0.97 to 1.43, P=0.10). No statistically significant differences of the incidence of hyperemia (RR 0.67, 95% CI 0.45 to 1.01, P=0.06) and eye irritation (RR 1.20, 95% CI 0.95 to 1.51, P=0.12) between the FCs and PGAs monotherapy were detected. Only one research involved in corneal events, result of this trial revealed no difference between two intervention groups regarding corneal effects (central endothelial cell density, MD -0.20, 95% CI -0.72 to 0.32, P=0.45; central corneal thickness, MD -0.01, 95% CI -0.02 to 0.00, P=0.23). The evaluation of visual field change was not performed due to the limited duration of the trials included in this Meta-analysis. CONCLUSION: The long-term efficacy of the FCs overweighed the PGAs monotherapy in lowering IOP, but in the incidence of hyperemia and eye irritation syndromes, the differences are not statically significant. More RCTs with detailed and authentic data over the assessments of visual functions and morphology of optic nerve heads are hoped to be conducted. PMID- 27275436 TI - Efficacy, safety, predictability, aberrations and corneal biomechnical parameters after SMILE and FLEx: Meta-analysis. AB - AIM: To identify possible differences of efficacy, safety, predictability, higher order aberrations and corneal biomechnical parameters after small-incision lenticule extraction (SMILE) and femtosecond lenticule extraction (FLEx). METHODS: A systematic literature retrieval was conducted in Medline, Embase and the Cochrane Library, up to October, 2015. The included studies were subject to a Meta-analysis. Comparison between SMILE and FLEx was measured as pooled odds ratio (OR) or weighted mean differences (WMD). Of 95% confidence intervals (CI) were used to analyze data. RESULTS: A total of seven studies were included. Firstly, there were no differences in uncorrected distance visual acuity (UDVA) 20/20 or better (OR, 1.37; 95% CI, 0.69 to 2.69; P=0.37) and logMAR UDVA (WMD, 0.02; 95% CI, -0.05 to 0.01; P=0.17) after SMILE versus FLEx. We found no differences in corrected distance visual acuity (CDVA) unchanged (OR, 0.98; 95% CI, 0.46 to 2.11; P=0.97) and logMAR CDVA (WMD, -0.00; 95% CI, -0.01 to 0.01; P=0.90) either. Secondly, we found no differences in refraction within +/-1.00 D (OR, 0.98; 95% CI, 0.13 to 7.28; P=0.99) and +/-0.50 D (OR, 1.62; 95% CI, 0.62 to 4.28; P=0.33) of target postoperatively. Thirdly, for higher-order aberrations, we found no differences in the total higher-order aberrations (WMD, -0.04; 95% CI, -0.09 to 0.01; P=0.14), coma (WMD, -0.04; 95% CI, -0.09 to 0.01; P=0.11), spherical (WMD, 0.01; 95% CI, -0.02 to 0.03; P=0.60) and trefoil (WMD, -0.00; 95% CI, -0.04 to 0.03; P=0.76). Furthermore, for corneal biomechanical parameters, we also found no differences (WMD, 0.08; 95% CI, -0.17 to 0.33; P=0.54) after SMILE versus FLEx. CONCLUSION: There are no statistically differences in efficacy, safety, predictability, higher-order aberrations and corneal biomechnical parameters postoperative between SMILE and FLEx. PMID- 27275437 TI - Unilateral visual impairment in rural south India-Andhra Pradesh Eye Disease Study (APEDS). AB - AIM: To report the prevalence and causes of unilateral visual impairment (UVI) in rural population of all ages in rural Andhra Pradesh, India. METHODS: A population-based cross sectional study using a multi-stage cluster sampling methodology was carried out in West Godavari, Adilabad and Mahbubnagar districts in south India. A comprehensive eye examination that included presenting and best corrected visual acuity and dilated fundus examination was conducted by trained professionals. UVI is defined as presenting visual acuity <6/18 in one eye but >=6/18 in other eye. Multiple logistic regression analysis was used to test association of UVI with socio-demographic risk factors. RESULTS: Data were analyzed for 6634/7771 participants after excluding those with bilateral visual impairment. The mean age of the participants was 27.4y (standard deviation: 17.9y), 51.9% were women and 49.1% were educated. The prevalence of UVI was 7.8% (95% CI: 7.2%-8.5%). Uncorrected refractive error (60.8%), cataract (17.4%) and retinal causes (6.6%) were the leading causes of UVI. On multiple logistic regression analyses, older age, not having education, living in well-off district had significantly higher odds of being associated with UVI. UVI was not associated with gender. CONCLUSION: UVI is common in rural south India. Most of it is due to cataract and refractive errors, both of which can be addressed at primary and secondary levels of eye care. Burden of UVI should also be considered in planning eye care services. PMID- 27275440 TI - Intravitreal triamcinolone acetonide: a "real world" analysis of visual acuity, pressure and outcomes. PMID- 27275441 TI - Hydration with Cefuroxime-a method for sealing a small leaking corneal perforation. PMID- 27275438 TI - Molecular underpinnings of corneal angiogenesis: advances over the past decade. AB - The cornea is maintained in an avascular state by maintaining an environment whereby anti-angiogenic factors take the upper hand over factors promoting angiogenesis. Many of the common pathologies affecting the cornea involve the disruption of such equilibrium and the shift towards new vessel formation, leading to corneal opacity and eventually-vision loss. Therefore it is of paramount importance that the molecular underpinnings of corneal neovascularization (CNV) be clearly understood, in order to develop better targeted treatments. This article is a review of the literature on the recent discoveries regarding pro-angiogenic factors of the cornea (such as vascular endothelial growth factors, fibroblast growth factor and matrix metalloproteinases) and anti-angiogenic factors of the cornea (such as endostatins and neostatins). Further, we review the molecular underpinnings of lymphangiogenesis, a process now known to be almost separate from (yet related to) hemangiogenesis. PMID- 27275442 TI - Homozygosity mapping of a consanguineous Pakistani family affected with oculocutaneous albinism to Tyrosinase gene. PMID- 27275439 TI - Ocular diseases: immunological and molecular mechanisms. AB - Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation. PMID- 27275443 TI - An update to monocanalicular stent surgery. PMID- 27275444 TI - Selected current data on metronomic therapy (and its promise) from India. PMID- 27275445 TI - An audit of the results of a triplet metronomic chemotherapy regimen incorporating a tyrosine kinase inhibitor in recurrent/metastatic head and neck cancers patients. AB - BACKGROUND: Addition of erlotinib to metronomic chemotherapy (MCT) may lead to further improvement in progression-free survival (PFS) and overall survival in head and neck cancers. The aim of this study was to study the PFS with MCT + erlotinib combination in our setting. METHODS: A single-arm prospective observational study conducted at Malabar Cancer Center. Patients warranting palliative chemotherapy for head and neck cancers, having adequate organ function, not-affording cetuximab and not willing for intravenous chemotherapy were included in this study. Oral methotrexate (15 mg/m(2)/week), oral celecoxib (200 mg twice daily), and erlotinib (150 mg once daily) were administered till the progression of the disease or till intolerable side-effects. Patients underwent toxicity (CTCAE version 4.02) and response (RECIST version 1.1) assessment every 30 days. Statistical analysis was performed using SPSS version 16 (IBM, New York, USA). Descriptive statistics and Kaplan-Meier analysis have been performed. RESULTS: A total of 15 patients received MCT. The median age of these patients was 65 years (range: 48-80). The Eastern Cooperative Oncology Group Performance Status was 0-1 in seven patients (46.7%), while it was 2 in eight patients (53.3%). The primary sites of tumor were predominantly oral cavity, 11 (73.4%). Prior to MCT, treatment with palliative radiation therapy was given in 11 patients and curative treatment in two patients. The best response post-MCT was complete remission in two patients, partial remission in seven patients, stable disease in four patients, and progressive disease in two patients. The median estimated PFS was 148 days (95% confidence interval 95.47 200.52 days). For a median follow-up of 181 days, there were only three deaths. Grade 3-4 toxicity was seen in six patients (40%). Dose reduction was required in four patients (26.7%). CONCLUSION: The addition of erlotinib to an MCT schedule of methotrexate and celecoxib resulted in a promising PFS and should be tested in future studies. PMID- 27275446 TI - Outcome of operable oral cavity cancer and impact of maintenance metronomic chemotherapy: A retrospective study from rural India. AB - BACKGROUND: Oral cavity cancer is the most common cancer among rural India. There is a paucity of data for outcomes of operable oral cavity cancer from rural India. Use of maintenance metronomic may delay or avoid relapse. AIM: To evaluate outcomes of operable oral cavity carcinoma and evaluate impact of maintenance metronomic chemotherapy. OBJECTIVES: To evaluate disease-free survival (DFS), overall survival (OS), and factors affecting the outcome in operable oral cavity cancer. MATERIALS AND METHODS: Data of patients diagnosed with oral cavity cancer registered between May 2008 and May 2014 were retrieved. Only those patients with operable oral cavity cancer and upfront definitive surgery were included in the study. Demographic profile, stage, tobacco consumption, adjuvant therapy, and pattern of failure were collected. Kaplan-Meir survival analysis was used to determine DFS and OS. Log-rank test was used to evaluate factors affecting outcome. RESULTS: Median follow-up is 24 months. Out of 335 patients, 225 (67%) had advanced operable cancer with 42/225 (18%) and 183/225 (82%) as Stages III and IVA, respectively. Buccal mucosa was the most common subsite (178/335, 53%) followed by tongue (63/335, 19%). Ninety-two percent patients were addicted to smokeless tobacco, whereas 27% were smokers. Median DFS is 13 months with 2 years relative DFS 32%. Median OS is 30 months, with 2 years OS of 54%. Metronomic adjuvant oral chemotherapy was given in 130/225 (58%); Stage III and IVA patients with median of 14 months (3-18 months). Use of metronomic chemotherapy improved DFS (8 vs. 14 months, P = 0.22) and OS (14 vs. 26 months, P = 0.04). CONCLUSION: Oral cavity cancer is a major health care problem in rural India. Presentation at advanced stage leads to suboptimal outcomes. Benefit of metronomic maintenance chemotherapy in locally advanced oral cavity needs to be further evaluated prospectively. PMID- 27275447 TI - Metronomic palliative chemotherapy in maxillary sinus tumor. AB - BACKGROUND: Metronomic chemotherapy consisting of methotrexate and celecoxib recently has shown promising results in multiple studies in head and neck cancers. However, these studies have not included patients with maxillary sinus primaries. Hence, the role of palliative metronomic chemotherapy in patients with maxillary sinus carcinoma that is not amenable to radical therapy is unknown. METHODS: This was a retrospective analysis of carcinoma maxillary sinus patients who received palliative metronomic chemotherapy between August 2011 and August 2014. The demographic details, symptomatology, previous treatment details, indication for palliative chemotherapy, response to therapy, and overall survival (OS) details were extracted. SPSS version 16 was used for analysis. Descriptive statistics have been performed. Survival analysis was done by Kaplan-Meier method. RESULTS: Five patients had received metronomic chemotherapy. The median age was 60 years (range 37-64 years). The proportion of patients surviving at 6 months, 12 months, and 18 months were 40%, 40%, and 20%, respectively. The estimated median OS was 126 days (95% confidence interval 0-299.9 days). The estimated median survival in patients with an event-free period after the last therapy of <6 months was 45 days, whereas it was 409 days in patients with an event-free period postlast therapy above 6 months (P = 0.063). CONCLUSION: Metronomic chemotherapy in carcinoma maxillary sinus holds promise. It has activity similar to that seen in head and neck cancers and needs to be evaluated further in a larger cohort of patients. PMID- 27275448 TI - Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience. AB - BACKGROUND: Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge. AIM: To evaluate outcomes of epithelial ovarian carcinoma. OBJECTIVES: To calculate disease-free survival (DFS), overall survival (OS), and factors affecting outcomes. MATERIALS AND METHODS: Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan-Meir survival was used to determine disease-free and OS. Log rank test used to evaluate factors affecting outcome. RESULTS: Median follow-up is 26 months. 93/102 patients (91%) underwent cytoreductive surgery, of which 37 had primary cytoreduction (40%) while 56 had interval cytoreduction. 21/93 (23%), 57/93 (61%), and 15/93 (16%) patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel platinum was used in 35/63 (56%) patients while 28/63 patients (44%) received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01), OS was 54 versus 26 months (P = 0.01).40/88 (45%) patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2 18 months). Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69). CONCLUSION: Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression. PMID- 27275449 TI - Bromide contamination in rice, cancer risk for consumer. PMID- 27275450 TI - Tolerance of weekly metronomic paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin. AB - OBJECTIVE: There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT) in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to examine the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. METHODS: Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly paclitaxel (80 mg/m(2)) and carboplatin AUC 2 as NACT. The data regarding the baseline characteristics, chemotherapy tolerance, completion rates, toxicity (Common Terminology Criteria for Adverse Events version 4.02), and radiological response rates are presented. SPSS version 16 was used for analysis. Descriptive statistics is presented. RESULTS: Eleven patients received this schedule. Nine patients completed nine cycles of NACT. Except one, all patients completed NACT with an average relative dose intensity of >0.8. There was no chemotherapy-related mortality. Grade 3-4 life-threatening complications were seen in two patients. The post NACT response rate was 100%. CONCLUSIONS: Weekly paclitaxel and carboplatin chemotherapy is safe and efficacious in patients who are unsuitable for 3 weekly paclitaxel and carboplatin chemotherapy schedules. PMID- 27275451 TI - Micrometastases in axillary nodes: Out of the reckoning? PMID- 27275452 TI - Weekly paclitaxel as metronomic palliative chemotherapy in small cell lung cancer. AB - BACKGROUND: Topotecan is the standard second line agent used in relapsed small cell lung cancer (SCLC). However, the erratic availability and the cost of the drug has been a prohibitive factor for its use in second-line setting in India. Paclitaxel has shown antitumor activity in heavily pretreated patients with SCLC. Hence, this audit was performed to study the efficacy of weekly paclitaxel as a form of metronomic therapy in the second-line setting in SCLC. MATERIALS AND METHODS: Fifty-seven patients of relapsed SCLC who presented to the thoracic medical oncology unit of Tata Memorial Centre, Mumbai between January 2011 and December 2015 were selected for this analysis. Weekly paclitaxel at a dose of 80 mg/m(2) was administered until progression or development of intolerable side effects or patient refusal. Data regarding baseline demographics, previous treatment history, response rate, progression-free survival, overall survival (OS), and toxicity to weekly paclitaxel was extracted from a prospectively maintained database in the thoracic medical oncology unit and was analyzed using SPSS version 16 (IBM, New York, USA). Kaplan-Meier survival analysis was performed. RESULTS: Median age of the cohort was 58 years (40-77 years). Etoposide with carboplatin was the regimen used in 40 patients (70.2%) whereas the remaining 17 patients received etoposide with cisplatin (29.8%). Eastern Cooperative Oncology Group performance status at relapse was 1 in 3 (5.3%), 2 in 49 (86.0%), and 3 in 5 (8.7%) patients. The response rate and clinical benefit rate were 9.1% (5 patients) and 52.7% (29 patients), respectively. Grade 3-4 toxicities were seen in 10.5% (6 patients). The median PFS was 145 days (95% confidence interval [CI]: 116.6-173.5 days) whereas the median OS was 168 days (95% CI: 112.5-223.5 days). CONCLUSION: Weekly paclitaxel as a second line agent in relapsed small cell cancer of the lung is a feasible and well-tolerated agent. PMID- 27275453 TI - Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: A prospective pilot study. AB - INTRODUCTION: Acute myeloid leukemia (AML) in elderly patients differs biologically from that in younger patients and is known to have unfavorable chromosomal rearrangements, higher resistance, and lower tolerance to chemotherapy. In such circumstances, instead of giving full-blown chemotherapy, palliative metronomic chemotherapy (MCT) could be a treatment option. PATIENTS AND METHODS: We performed a prospective pilot study of old AML patients (age >60 years) not amenable to curative treatment. Thirty-two patients were enrolled into the study and were treated with daily oral 6-mercaptopurine 75 mg/m(2). The following inclusion criteria were used: age >60 years, nonpromyelocytic AML, the absence of uncontrolled comorbidities, and patient not amenable to curative treatment. Overall survival (OS) was calculated using Kaplan-Meier method and Cox regression analysis were used to calculate the hazards ratio of significant factors. RESULTS: The median age of the patients was 69 years (range: 61-86 years) with male: female ratio of 2.5:1. About 59.4% of patients had Eastern Cooperative Oncology Group performance status of 2 while rest had the status of 3. The median OS was 6 months (95% confidence interval [CI]: 4.4-7.6). Males had median OS of 7 months (95% CI: 5.4-8.6) versus females with OS of 3 months (95% CI: 1.5-4.4; P = 0.008). There was no survival difference on the basis of baseline hemoglobin or French-American-British class. There were no Grade 4 toxicities and no episode of febrile neutropenia. CONCLUSIONS: MCT with oral 6 mercaptopurine is an attractive treatment option in elderly AML patients who are not amenable to curative therapy with minimal toxicities. PMID- 27275454 TI - Evaluation of p16 hypermethylation in oral submucous fibrosis: A quantitative and comparative analysis in buccal cells and saliva using real-time methylation specific polymerase chain reaction. AB - AIMS: The aim of this study was to quantitatively investigate the hypermethylation of p16 gene in buccal cells and saliva of oral submucous fibrosis (OSMF) patients using real-time quantitative methylation-specific polymerase chain reaction (PCR) and to compare the values of two methods. SUBJECTS AND METHODS: A total of 120 samples were taken from 60 subjects selected for this study, of which 30 were controls and 30 patients were clinically and histopathologically diagnosed with OSMF. In both groups, two sets of samples were collected, one directly from the buccal cells through cytobrush technique and the other through salivary rinse. We analyzed the samples for the presence of p16 hypermethylation using quantitative real-time PCR. RESULTS: In OSMF, the hypermethylation status of p16 in buccal cells was very high (93.3%) and in salivary samples, it was partially methylated (50%). However, no hypermethylation was found in controls suggesting that significant quantity of p16 hypermethylation was present in buccal cells and saliva in OSMF. CONCLUSIONS: This study indicates that buccal cell sampling may be a better method for evaluation than the salivary samples. It signifies that hypermethylation of p16 is an important factor to be considered in epigenetic alterations of normal cells to oral precancer, i.e. OSMF. PMID- 27275455 TI - Limitations of cytological cervical cancer screening (Papanicolaou test) regarding technical and cultural aspect in rural India. PMID- 27275456 TI - Long term results of comparison of concurrent low-dose daily cisplatin versus the standard weekly cisplatin with six fractions per week radiotherapy in locally advanced head neck cancer. AB - AIM AND OBJECTIVE: Weekly administration of cisplatin (cis diamminedichloroplatinum [CDDP]) appears more feasible and substantially more popular than the 3 weekly schedules due to better compliance. Different concurrent cisplatin schedules have been attempted including a daily schedule. We did a comparison of two consecutive single arm studies, i.e., use of weekly cisplatin versus daily cisplatin when used with concurrently with a moderately accelerated radiotherapy (RT) schedule. PATIENTS AND METHODS: Two prospective feasibility, safety and efficacy studies were carried out consecutively within the department. The weekly CDDP study was done from August 2003 to August 2005 and daily CDDP study was conducted from November 2005 to June 2007. Both studies included locally advanced stage III and IV squamous cell carcinoma of the head and neck region with RT dose of 70 Gy. Concurrent single-agent cisplatin was administered weekly (35 mg/m(2)) in the first and daily (6 mg/m(2)) in the second study. RESULTS: Weekly cisplatin study had 68 and daily CDDP study had 52 patients. The median follow-up in the two studies was 93 and 63 months, respectively. Compliance in the two studies was comparable. Acute Grade III/IV mucositis and dysphagia were significantly higher in weekly cisplatin study. Late Grade II/III toxicities such as xerostomia, dysphagia, ototoxicity and nephrotoxicity were similar. The 5 years locoregional control was 18% and 25% and 5 years overall survival rate was 32% and 31% in weekly and daily cisplatin studies, respectively. CONCLUSIONS: Modest acceleration along with either weekly or daily cisplatin, whichever is possible in one's setup, is do-able, provided due attention is paid to patient selection and supportive care. PMID- 27275457 TI - Acute Respiratory Distress Syndrome and Posterior Reversible Encephalopathy Syndrome following Rituximab Therapy. AB - The anti-CD20 monoclonal antibody rituximab is associated with rare but significant adverse events, notably posterior reversible encephalopathy syndrome (PRES) and acute respiratory distress syndrome (ARDS). We report a case of concomitant ARDS and PRES developing after rituximab therapy for treatment of cryoglobulinaemic vasculitis. There are 7 reported cases of PRES complicating rituximab use. PRES onset varied from immediate to 21 days after administration. All patients recovered completely, and rituximab was reintroduced in half of the cases. The occurrence of ARDS in association with rituximab is rarer. Only 3 confirmed cases exist, and ARDS may occur as a delayed reaction. PMID- 27275458 TI - Hormonal control of the metabolic machinery of hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide. It is an aggressive cancer with low cure rate, frequent metastasis, and highly resistant to conventional chemotherapies. Better knowledge regarding the molecular and metabolic alterations in HCC will be instrumental to the development of novel therapeutic interventions against HCC. In the August 2015 issue of Hepatology, Nie et al. reports an important molecular pathway that contributes to the Warburg Effect in HCC. They have beautifully demonstrated that the loss of a component of a hormonal system, the mineralocorticoid receptor (MR), reprogrammed the metabolic machinery of HCC cells to aerobic glycolysis through the miR-338-3p-PKL/R axis. The implication could be that in addition to drugs that directly target the metabolic enzymes in cancer cells, more translational efforts could be focused on the development of drugs that involve the activation of the MR-aldosterone system or other hormonal systems to target the Warburg effect. PMID- 27275459 TI - Circulating microRNAs for early detection of hepatitis B-related hepatocellular carcinoma. PMID- 27275460 TI - STAT3 is a key transcriptional regulator of cancer stem cell marker CD133 in HCC. AB - Cancer stem cell (CSC) marker CD133 was found to be upregulated in many cancers including hepatocellular carcinoma (HCC). However, the molecular mechanism of CD133 regulation in the liver tumor microenvironment has remained elusive. In this study Won and colleagues report that interleukin-6 (IL-6) mediated signal transducer and activator of transcription factor 3 (STAT3) signaling and hypoxia enhance the expression of CD133 and promote the progression of HCC. PMID- 27275461 TI - In vitro three dimensional culture of hepatocellular carcinoma to measure prognosis and responsiveness to chemotherapeutic agents. AB - BACKGROUND: Understanding the prognosis of hepatocellular carcinoma (HCC) informs plans for care. Tumor morphology and molecular markers have been correlated with outcomes. Three-dimensional tissue culture (3DTC) allows for direct in vitro measurement of a tumor's ability to grow and metastasize. The impact of chemotherapeutic agents, alone or in combinations, may also be measured. METHODS: All patients with a presumed diagnosis of HCC were eligible for this study including those undergoing resection, chemoembolization and transplantation. Concomitant diseases and outcomes were recorded. One mm(3) HCC specimens were grown in multiwell plates containing gel media, without and with chemotherapeutic agents. RESULTS: Tumors were sampled from 17 patients. Only 13 had HCC, all of whom had liver transplantation. Of the confirmed HCC patients, 6 (46%) are alive and disease free 82 months following transplantation, 1 (7%) is alive with recurrence of disease and 6 (46%) died, with a mean survival of 12 months post liver transplant. Ten of thirteen 3DTC samples grew, having an average migration distance of 108.3um in the first 24 hours. Two of three patients who had prior chemoembolization had successful 3DTC. Migration distances (um) were 188.8+/ 104.3, 104.5+/-111.7 and 39.6+/-32.4 for tumors categorized as high, intermediate and low grade, respectively. Tumor migration was inhibited by irinotecan, paclitaxel and docetaxel (-68%+/-7%, -61%+/-19% and -60%+/-21%, respectively) whereas the effect was variable with 5 fluorouracil (5FU) and doxorubicin (-12%+/ 51% and 9%+/-76%, respectively). CONCLUSIONS: It is feasible to grow tissue from HCC in 3DTC to study the tumor's capacity to grow and migrate and its responsiveness to commonly used chemotherapeutic protocols. PMID- 27275462 TI - Ophthalmological side effects of interferon therapy of chronic hepatitis C. AB - BACKGROUND: Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity. METHODS: We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment. RESULTS: IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy. CONCLUSIONS: Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately it's asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important. PMID- 27275463 TI - Hypophosphatemia and recovery of post-hepatectomy liver insufficiency. AB - BACKGROUND: Hypophosphatemia (HP) is frequent following liver resection, and thought to represent use of phosphate during liver regeneration. We sought to evaluate the association of post-hepatectomy HP with liver insufficiency and recovery. METHODS: Liver resections were retrospectively reviewed from 2009 to 2012 at a single institution. We explored the relationship between HP (defined as serum phosphate <=0.65 mmol/L), occurrence of initial liver insufficiency (ILI) [bilirubin >50 umol/L, international normalized ratio (INR) >1.7 within 72 hours of surgery] and in-hospital recovery of ILI. Secondary outcomes included 30-day post-operative major morbidity (Clavien grade 3 and 4 complications), mortality, and re-admission. RESULTS: Among 402 patients, 223 (55.5%) experienced HP and 64 (15.9%) met our definition of ILI, of which 53 (82.8%) recovered. Length of stay, 30-day post-operative major morbidity, mortality, and re-admission were similar between patients with and without HP. Among patients with ILI, 44 (68.8%) experienced HP. Following ILI, patients with HP recovered more often than those with NP (90.9% vs. 65.0%; P=0.03). CONCLUSIONS: In patients who experience post hepatectomy ILI, HP is associated with improved recovery, potentially indicating more efficient liver regeneration. Further studies should explore the usefulness of post-hepatectomy HP as an early prognostic factor of recovery from ILI. PMID- 27275464 TI - Radiofrequency and microwave ablation in combination with transarterial chemoembolization induce equivalent histopathologic coagulation necrosis in hepatocellular carcinoma patients bridged to liver transplantation. AB - BACKGROUND: Bridging therapy plays an increasingly important role in the management of patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). Combination therapy with drug-eluting bead transarterial chemoembolization (DEB-TACE) and percutaneous thermal ablation, such as radiofrequency ablation (RFA) or microwave ablation (MWA), has shown success at prolonging survival and bridging patients to LT. However, few studies have evaluated the two combination therapy regimens head-to-head at a single institution, and fewer have compared histopathology. This retrospective study compares tumor coagulation on explanted livers in patients with HCC treated with DEB-TACE sequentially combined with RFA versus MWA. METHODS: From 2005 to 2015, 42 sequential patients underwent combination therapy prior to LT by Milan criteria, with 11 patients (11 tumors; mean, 2.9 cm; range, 1.8-4.3 cm) in the DEB-TACE/RFA cohort and 31 patients (40 tumors; mean, 2.4 cm; range, 1.1-5.4 cm) in the DEB-TACE/MWA cohort. The mean TACE procedures in the RFA and MWA cohorts were 1.3 (range, 1-2) and 1.3 (range, 1-3), respectively. The mean thermal ablations in the RFA and MWA cohorts were 1.2 (range, 1-2) and 1.3 (range, 1-3), respectively. Tumor coagulation was evaluated on explanted livers. RESULTS: Mean tumor coagulation in the RFA and MWA cohorts were 88.9% (range, 0-100%) and 90.5% (range, 30-100%), respectively (P=0.82). Rates of complete tumor coagulation in the RFA and MWA cohorts were 45% and 53%, respectively (P=0.74). No difference in tumor coagulation was found between the cohorts when separating tumors <3 cm (P=0.21) and >3 cm (P=0.09). Among all 51 tumors, the 36 in complete response (CR) on imaging at LT demonstrated mean tumor coagulation of 95.8%. No correlation was found between tumor coagulation and initial tumor size or time interval to LT. No tumor seeding was seen along the ablation tracts. CONCLUSIONS: RFA and MWA in sequential combination with DEB-TACE, used as a bridge to LT, are equally efficacious at inducing HCC tumor coagulation. PMID- 27275465 TI - Societal reintegration following cadaveric orthotopic liver transplantation. AB - BACKGROUND: Studies on patients' societal reintegration following orthotopic liver transplantation (OLT) are scarce. METHODS: Between September 2006 and January 2008, all adults who were alive after 3 years post OLT were included in this prospective cohort study. Validated questionnaires were administered to all candidates with the primary aim of investigating the rate of their social re integration following OLT and potential barriers they might have encountered. RESULTS: Among 157 eligible patients 110 (70%) participated. Mean participants' age was 57 years (SD 11.4) and 43% were females. Prior to OLT, 75% of patients were married and 6% were divorced. Following OLT there was no significant difference in marital status. Employment rate fell from 72% to 30% post-OLT. Patients who had been employed in either low-skill or advanced-skill jobs were less likely to return to work. After OLT, personal income fell an average of 4,363 Canadian dollars (CAN$) (SD 20,733) (P=0.03) but the majority of recipients (80%) reported high levels of satisfaction for their role in society. CONCLUSIONS: Although patients' satisfaction post-OLT is high, employment status is likely to be negatively affected for individuals who are not self-employed. Strategies to assist recipients in returning to their pre-OLT jobs should be developed to improve patients' economical status and societal ability to recoup resources committed for OLT. PMID- 27275466 TI - Laparoscopic long sleeve pancreaticogastrostomy (LPG): a novel pancreatic anastomosis following central pancreatectomy. AB - BACKGROUND: Central pancreatectomy (CP) is preferred to distal pancreatectomy (DP) for the excision of benign tumours at the neck or body of the pancreas, in order to preserve pancreatic function and the spleen. However, the pancreaticoenterostomy is technically difficult to perform laparoscopically and the postoperative pancreatic fistula (POPF) rate is high. METHODS: A novel laparoscopic reconstruction of the pancreatic stump during CP is described, the laparoscopic long sleeve pancreaticogastrostomy (LPG). RESULTS: Two males and two females with a median age of 49 years had a laparoscopic CP with LPG. After a median follow-up of 27.5 months, there was no mortality. One patient had a grade A POPF, managed conservatively. CONCLUSIONS: The LPG is a safe and technically less demanding method to reconstruct pancreatic drainage laparoscopically. PMID- 27275467 TI - Losartan may inhibit the progression of liver fibrosis in chronic HCV patients. AB - BACKGROUND: Abundant experimental evidence indicates overproduction of angiotensin II in the injured liver, and a role in stimulation of hepatic stellate cell (HSC) activation and fibrogenesis thereby, representing an attractive antifibrotic target. The aim of this study was to examine the antifibrotic effect of losartan on histopathologic level in chronic HCV patients. METHODS: A prospective study on fifty patients with chronic HCV and liver fibrosis proved by liver biopsy was conducted. They included patients who did not respond (n=36) or comply (n=2) or receive therapy due to established cirrhosis (n=10), or refused to receive (n=2) combined interferon and ribavirin therapy. They were divided randomly into 2 groups. The 1(st) group (n=25) was given losartan 50 mg OD for 1 year and the 2(nd) group (25 patients) was given silymarin, 140 mg t.i.d., (silymarin group). Liver biopsy was done at baseline and 1 year from the onset of treatment (end of study). RESULTS: In the second liver biopsy after 1 year, the decrease in fibrosis stage was significantly different between losartan group and silymarin group (a decrease of 1.88+/-0.96 (50.9%) vs. 0.45+/-0.93 (11.7%), respectively; P<0.01). In patients treated with losartan, regression in fibrosis stage was observed in 14/16 patients vs. 2/11 in silymarin group (P<0.01). No differences were observed in inflammation grades in both groups. A significant increase in albumin and prothrombin levels and a decrease in systolic blood pressure were found in losartan but not in silymarin group (P=0.009, 0.001 & 0.018 respectively and P=0.158, 0.603 & 0.288, respectively). CONCLUSIONS: Histopathological scores showed that losartan had an inhibitory effect on progression and even led to regression of fibrosis stage but had no effect on the grade of inflammation. PMID- 27275469 TI - Spontaneous bilateral adrenal hemorrhage following cholecystectomy. AB - Postoperative bilateral adrenal hemorrhage is a rare but potentially life threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment. PMID- 27275468 TI - Preoperative body mass index-to-prognostic nutritional index ratio predicts pancreatic fistula after pancreaticoduodenectomy. AB - BACKGROUND: Estimating or scoring the risk of post-operative pancreatic fistula (POPF) may help with selection of high-risk patients and individualized patient consent. However, there are no simple and reliable preoperative predictors of POPF used in daily clinical practice. METHODS: We investigated the utility of body mass index-to-prognostic nutritional index (BMI/PNI) ratio as a preoperative marker to predict the development of POPF in 87 patients undergoing pancreaticoduodenectomy. RESULTS: The overall incidence of clinical (grade B/C) POPF was 17% (15 of 87 patients). Among various pre-, intra-, and post-operative variables analyzed, higher BMI and lower PNI were identified as independent predictors for POPF by multivariate analysis. We therefore investigated BMI/PNI ratio as a preoperative predictor for POPF. BMI/PNI ratio was significantly higher in patients with POPF than in those without POPF (0.54 vs. 0.45, P=0.0007). A receiver operating characteristic (ROC) curve analysis demonstrated a fair capability of BMI/PNI ratio to predict the occurrence of POPF (area under the ROC curve 0.781). With a cut-off value of 0.5, the sensitivity, specificity, and diagnostic accuracy of BMI/PNI ratio to predict POPF was 73%, 74%, and 74%, respectively. In particular, when restricted to a subgroup of elderly (>=75 years old) male patients, the sensitivity, specificity, and diagnostic accuracy of BMI/PNI ratio was 100%, 100%, and 100%, respectively. CONCLUSIONS: The BMI/PNI ratio is a simple preoperative marker to predict the occurrence of POPF after pancreaticoduodenectomy. PMID- 27275470 TI - An unusual case of adrenocortical carcinoma with liver metastasis that occurred at 23 years after surgery. AB - Adrenocortical carcinoma (ACC) is an uncommon and aggressive cancer occurring more frequently in women; local or distant recurrences occur in 80% of cases, typically within 1 year after curative resection. Liver is the preferred metastatic site. Herein, we report the case of a unique liver metastasis from ACC occurring 23 years after the curative prior tumor surgery. A 45-year-old woman was operated in 1991 for adrenocortical stage II without microvascular involvement or capsular infiltration. At that time, no adjuvant treatment was indicated. The initial surgery consisted on a left adrenalectomy with contemporaneous left nephrectomy and regional lymphadenectomy. Five years after surgery, the patient was considered cured. However, 23 years later, the patient presented an atypical right subcostal pain. A 4 cm liver ACC metastasis involving the segment 4 and initially diagnosed as a hemangioma was discovered. A curative resection of the segment 4 was performed. Final pathological examination confirmed the diagnosis of ACC metastasis with a complete R0 resection; no lymph node metastases were observed. This case is the latest metachronous ACC metastasis ever reported in literature. To date, the patient is alive with no signs of recurrence after a post-surgical follow-up of 13 months. PMID- 27275471 TI - The veno-venous bypass in liver transplantation: an unfinished product. AB - Veno-venous bypass (VVB) using a patent para-umbilical vein during liver transplantation (LT) has not been reported previously. Here, we report the decompression of the porto-mesenteric compartment via a patent para-umbilical vein in a patient needing a VVB during LT. Pre-transplant CT-scan showed a large patent para-umbilical vein. A femoro-axillary percutaneous VVB was installed prior to abdominal opening to decompress massive collateral veins in the abdominal wall. The para-umbilical vein was stapled and its proximal end was cannulated and connected to the VVB. The severe atrophy of the native liver allowed to place the whole liver graft in the "liver fossa" while maintaining the native liver pulled toward the left side and connected to the VVB. This maneuver maintained splanchnic venous decompression during latero-lateral cavo-caval anastomosis. The "portal" cannula was clamped and removed. The native portal vein was clamped and divided. Standard portal, arterial, and biliary reconstructions were then performed. A patent para-umbilical vein, present in one third of patients with portal hypertension could be used whenever VVB is indicated during LT in this setting. PMID- 27275473 TI - Dr. Matteo Donadon: the status of hepatic resection in Italy. PMID- 27275472 TI - Spontaneous erosion of peripancreatic catheter into the duodenum: an unforeseen complication of percutaneous drainage. PMID- 27275474 TI - Prognostic factors for long term survival in patients with advanced non-small cell lung cancer. AB - BACKGROUND: Non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. It is estimated that 60% of patients with NSCLC at time of diagnosis have advanced disease. The aim of this study was to investigate clinical and demographic prognostic factors of long term survival in patients with unresectable NSCLC. METHODS: We retrospectively reviewed data of 1,156 patients with NSCLC stage IIIB or IV who survived more than 60 days from the time of diagnosis and treated from August 1987 until March 2013 in the Oncology Department of Pulmonary Clinic of the General Hospital Papanikolaou. Initially univariate analysis using the log-rank test was conducted and then multivariate analysis using the proportional hazards model of Cox. Also Kaplan Meier curves were used to describe the distribution of survival times of patients. The level of significance was set at 0.05. RESULTS: The mean age at diagnosis was 62 years. About 11.9% of patients were women and 88.1% were male. The majority of cases were adenocarcinomas (42.2%), followed squamous (33%) and finally the large cell (6%). Unlike men, most common histological type among women was adenocarcinoma rather than squamous (63% vs. 10.9%). In univariate analysis statistically significant factors in the progression free survival (PFS) and overall survival (OS) were: weight loss >=5%, histological type, line 1 drugs, line 1 combination, line 1 cycles and radio lung. Specifically radio lung gives clear survival benefit in the PFS and OS in stage IIIB (P=0.002) and IV (P<0.001). On the other hand, the number of distant metastases in stage IV patients did not affect OS, neither PFS. In addition patients who received platinum and taxane had better PFS (P=0.001) and OS (P<0.001) than those who received platinum without taxane. Also the third drug administration proved futile, since survival (682.06+/-34.9) (P=0.023) and PFS (434.93+/-26.93) (P=0.012) of patients who received less than three drugs was significantly larger. Finally, large cell carcinoma recorded the shortest OS and PFS compared with adenocarcinoma (P=0.043 and P=0.016 respectively) and squamous cell carcinoma (P=0.021 and P=0.004 respectively). In multivariate analysis the same predictors were statistically significant except for line 1 drugs. CONCLUSIONS: This study confirms the increased incidence of adenocarcinoma in women than in men and the aggressiveness of large cell carcinoma. It also underlines the vitality of factors such as weight loss, radio lung and doublet platinum-based. On the other hand, it excludes significant factors such as gender, age and smoking. PMID- 27275475 TI - A pilot study-is there a role for mitoxantrone pleurodesis in the management of pleural effusion due to lung cancer? AB - BACKGROUND: Lung cancer is the leading cause of malignant pleural effusion (MPE). Management of MPEs remains a clinical challenge due to recurrence and poor quality of life. An ideal sclerosing agent has yet to be found. The aim of this cohort pilot study was to evaluate the role of mitoxantrone pleurodesis (MP) as an alternative to talc sclerotherapy for managing MPEs in lung cancer patients. METHODS: A retrospective chart review was conducted on consecutively admitted patients with MPE to the Department of Post-Intensive Care at the Clinic for Respiratory Diseases "Jordanovac", University Hospital Centre Zagreb, in Croatia. RESULTS: Of 34 patients with MPE, twenty-one (64.8+/-9.46 years; 47-84 years) with primary lung carcinoma who received MP (30 mg of mitoxantrone) between December 2003 and February 2009 were included in this study. Chest radiographs taken prior to sclerotherapy and at 1-, 2-, and 3-month follow-up were compared. At the post-sclerotherapy evaluation periods, overall success (OS) rates of MP were 88.2% [17.6%, complete response (CR); 70.6%, partial response (PR)], 53.9% (7.7% CR; 46.2% PR), and 45.5% (PR), respectively. Kaplan-Meier median survival from MP until death was 5.2 months, while that from diagnosis of primary lung cancer was 12.3 months. CONCLUSIONS: MP may be a safe and effective method of managing MPE due to lung cancer. Future randomized controlled studies comparing mitoxantrone and talc pleurodesis in lung cancer patients are warranted to elucidate whether a significant difference exists between these agents. Factors affecting success, survival probability, and quality of life also require further investigation. PMID- 27275476 TI - Biliary tract injuries after lap cholecystectomy-types, surgical intervention and timing. AB - Bile duct lesions, including leaks and strictures, are immanent complications of open or laparoscopic cholecystectomy (LC). Endoscopic procedures have gained increasing potential as the treatment of choice in the management of postoperative bile duct injuries. Bile duct injury (BDI) is a severe and potentially life-threatening complication of LC. Several series have described a 0.5% to 0.6% incidence of BDI during LC. Early recognition and an adequate multidisciplinary approach are the cornerstones for the optimal final outcome. Suboptimal management of injuries often leads to more extensive damage to the biliary tree and its vasculature. Early referral to a tertiary care center with experienced hepatobiliary surgeons and skilled interventional radiologists would appear to be necessary to assure optimal results. PMID- 27275477 TI - Increasing incidence of colon cancer in patients <50 years old: a new entity? AB - Colorectal cancer (CRC) is the third most common cancer type in humans, the fourth most common cause of death because of cancer, and the second most common cancer type in terms of the number of individuals living with cancer 5 years after diagnosis worldwide, almost 694,000 people die from CRC annually. As it is expected is more frequent in older patients (patients older than 70 years old than in young patients (patients younger than 40 years old). The incidence of CRC in young adults is rising the last years and this fact arises the question; is this coincidence or is young adult CRC a real epidemy. In our current commentary we try and elucidate based on current data whether disease on young individuals is a new entity. PMID- 27275479 TI - Thoracic duct cyst of posterior mediastinum: a "challenging" differential diagnosis. AB - Thoracic duct cysts of the mediastinum are extremely rare entities and their pathogenesis still remains unknown. Imaging methods are not specific and show a cystic mass, however the real nature of the lesion is confirmed only with the help of histopathological examination after surgical excision. Here, we present a case of thoracic cyst in a 28-year-old female, lining in posterior lower mediastinum. The cyst was removed by video-assisted thoracic surgery (VATS) and the histopathological findings were that of thoracic duct cyst. Through this case, we propose an ideal surgical approach and diagnostic procedure. PMID- 27275480 TI - Isolated polycystic liver disease and aneurism: a case report. AB - Isolated polycystic liver disease (PCLD) has not been associated with aneurysms and concomitant PLD has not been reported previously in association with bilateral popliteal aneurysms. A case of a middle-aged man with PLD, marfanoid habitus and bilateral popliteal aneurysms is presented. PMID- 27275478 TI - Pancreatic cancer from bench to bedside: molecular pathways and treatment options. AB - In the last forty years the pancreatic cancer treatment has made advances, however; still novel drugs are needed. It is known that the five year survival rate remains around 5%. The best treatment option still remains surgery, if patients are diagnosed early. In the last decade the biology of pancreatic cancer has been vastly explored and novel agents such as; tyrosine kinase agents, or vaccines have been added as a treatment perspective. The big challenge is now to translate this knowledge in better outcomes for patients. In this current review we will present information from pancreatic cancer diagnosis to molecular pathways and treatment options; current and future. PMID- 27275481 TI - Use of GeneXpert Mycobacterium tuberculosis/rifampicin for rapid detection of rifampicin resistant Mycobacterium tuberculosis strains of clinically suspected multi-drug resistance tuberculosis cases. AB - BACKGROUND: Multi-drug resistance (MDR) TB is defined as tuberculosis (TB) disease caused by a strain of Mycobacterium tuberculosis (MTB) that was resistant to at least isoniazid and rifampicin (RIF). Emerging Multidrug-Resistant TB is one of the major concerns of health policy and rapid detection of M. tuberculosis and detection of RIF resistance in infected patients are essential for disease management. The aim of this study was to evaluate patterns of RIF resistance in cases of sputum positive pulmonary TB by using GeneXpert MTB/RIF and comparing between phenotypic and genotypic testing of RIF resistance in MTB strains of clinically suspected MDR-TB isolated cases in western Algeria. METHODS: In this study 50 sputum positive cases of pulmonary TB who were potential MDR suspect were included. Their sputum samples were collected and subjected to sputum smear microscopy, culture and conventional MTB/RIF test followed by GeneXpert MTB/RIF assay. RESULTS: Of total 50 cases included in this study, MTB was detected in all patients (100%) by GeneXpert MTB/RIF. However, RIF's resistance was detected in only 21 cases (42%) by GeneXpert MTB/RIF. All RIF resistant strains detected by GeneXpert MTB/RIF were phenotypically confirmed as MDR strains. 42.85% of cases were retreatment failure cases, retreatment cases smear positive at 4 months were 23.82%. While 19.05% of cases were retreatment cases smear positive at diagnosis, and 14.28% patient had history of contact with MDR-TB. Sensitivity, specificity, positive predictive value and negative predictive value of Xpert MTB/RIF to detect RIF resistance in comparison to conventional phenotypic drug susceptibility technique were found equal to the rates of 100%, 100%, 100% and 100%, respectively. CONCLUSIONS: GeneXpert MTB/RIF assay is efficient and reliable technique for the rapid diagnostic of TB. It's simplicity, high sensitivity and specificity for RIF resistance detection make this technique a very attractive tool for diagnostic of MTB and RIF resistance in MDR cases. PMID- 27275482 TI - Cross table lateral radiography for measurement of acetabular cup version. AB - BACKGROUND: Appropriate orientation of the acetabular cup is an important factor for long-term results of total hip arthroplasty. For measurement of cup version cross-table lateral radiography is frequently used, but the reliability has been questioned. We compared cross table lateral radiography with computed tomography in patients that had undergone primary total hip arthroplasty. METHODS: The study was prospectively done in 117 patients (117 hips). At 3 months after total hip replacement the acetabular version was measured by cross table lateral radiography and compared to measurements by computed tomography. RESULTS: By cross table lateral radiography acetabular anteversion was on mean 13.9 degrees with a standard deviation of 10.1 degrees as compared to 17.8 degrees +/-12.6 degrees by computed tomography. Mean difference was -3.8 with a distribution of measurements of +/-13 degrees for 95% of the cases. CONCLUSIONS: Our study shows that cross table radiography provides acceptable information for clinical use, but has limited use for precise analysis of acetabular cup version. PMID- 27275483 TI - Gene expression profile of THP-1 cells treated with heat-killed Candida albicans. AB - BACKGROUND: Mechanisms under immune response against Candida albicans (C. albicans) remain largely unknown. To better understand the mechanisms of innate immune response against C. albicans, we analyzed the gene expression profile of THP-1 cells stimulated with heat-killed C. albicans. METHODS: THP-1 cells were stimulated with heat-killed C. albicans for 9 hours at a ratio of 1:1, and gene expression profile of the cells was analyzed using Whole Human Genome Oligo Microarray. Differentially expressed genes were defined as change folds more than 2 and with statistical significance. Gene ontology (GO) and pathway analysis were used to systematically identify biological connections of differentially expressed genes, as well as the pathways associated with the immune response against C. albicans. RESULTS: A total of 355 genes were up-regulated and 715 genes were down-regulated significantly. The up-regulated genes were particularly involved in biological process of RNA processing and pathway of the spliceosome. In case of down-regulated genes, the particularly involved immune-related pathways were G-protein coupled receptor signaling pathway, calcium signaling pathway, MAPK signaling pathway and Ras pathway. CONCLUSIONS: We depict the gene expression profile of heat-killed C. albicans stimulated THP-1 cells, and identify the major pathways involved in immune response against C. albicans. These pathways are potential candidate targets for developing anti-C. albicans agent. PMID- 27275484 TI - Determining the incidence of the hereditary form of retinoblastoma. AB - Retinoblastoma (Rb) is used here as the prototype of a condition which has a dominant mode of inheritance. Under the two-hit model of carcinogenesis, a germinal mutation may be followed by somatic mutation producing a tumour or tumours, in which case the carrier has relatively lower fitness. If somatic mutation does not occur, the carrier is assumed to have normal fitness, that is the Rb germinal mutation is incompletely penetrant. Formulae are given for the frequency of the Rb allele and the incidence of Rb in equilibrium as functions of the mutation rate, penetrance and fitness. PMID- 27275485 TI - Uveal melanoma as a target for immune-therapy. AB - Uveal melanoma (UM) is a rare disease that can be deadly in spite of adequate local treatment. Systemic therapy with chemotherapy is usually ineffective and new-targeted therapies have not improved results considerably. The eye creates an immunosuppressive environment in order to protect eyesight. UM cells use similar processes to escape immune surveillance. Regarding innate immunity the production of macrophage inhibiting factor (MIF) and TGF-beta, added to MHC class I upregulation, inhibits the action of natural killer (NK) cells. UM cells produce cytokines such as IL-6 and IL-10 that favor macrophage differentiation to the M2 subtype, which promote tumor growth instead of an effective immune response. UM cells also impair the adaptive immune response through production of indoleamine 2,3-dioxygenase (IDO), overexpression of programmed death ligand-1 (PD-L1), alteration of FasL expression, and resistance to perforin. This biological background suggests that immunotherapy could be effective in fighting UM. A Phase II clinical trial with Ipilimumab has shown promising results with mean Overall Survival rate of ten months, and close to 50% of the patients alive at one year. Clinical trials with anti-PD1 antibodies in monotherapy and in combination with anti-CTLA4 are currently recruiting patients worldwide. PMID- 27275487 TI - Multivariable fractional polynomial method for regression model. PMID- 27275486 TI - The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications. AB - Head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, with low survival rates for advanced stage tumors and minimal improvement in survival trends through the past decades. It is becoming increasingly clear that HNSCC oncogenesis and evolution is characterized by profound immune defects, as cancer cells evade immunosurveillance due to accumulation of genetic mutations and tumor heterogeneity. Improved understanding of the role of the immune system in cancer has led to the identification of novel therapeutic targets, which are being investigated for their potential to provide durable responses. In this review, we will summarize the role of the immune system in HNSCC, the rationale behind immunotherapy strategies and their clinical applications. PMID- 27275488 TI - Successful management of H1N1 related severe acute respiratory distress syndrome with noninvasive positive pressure ventilation. AB - Acute respiratory distress syndrome (ARDS) is a life threatening complication of H1N1 pneumonia. According to the Berlin conference guidelines, severe ARDS requires management with early invasive mechanical ventilation. Whether noninvasive positive pressure ventilation (NIPPV) should be attempted in patients with H1N1 pneumonia is still a matter of debate. We report the case of one patient with severe ARDS without other organ failure. The patient was managed successfully using NIPPV. Endotracheal intubation was avoided and the patient was discharged from the intensive care unit (ICU) after 10 days with a successful outcome. NIPPV can be useful in patients with isolated severe H1N1 ARDS provided early improvement of the oxygenation parameters is achieved. Patients with multiple organ failure or with persistent severe hypoxemia under noninvasive ventilation should be electively intubated and started on invasive mechanical ventilation. PMID- 27275489 TI - Presacral schwannoma: laparoscopic resection, a viable option. AB - Schwannomas are benign nerve sheath tumours arising from Schwann cells. Presacral schwannomas are rare with only case report and short case series being reported in literature. Complete surgical resection is the treatment of choice for these rare tumours. Approach to surgical resection depends on the type of the tumour. Type 3 tumours have conventionally been treated with open intra or extra peritoneal approach. With improvement in the laparoscopic surgical skills, more and more complex surgical procedures have been attempted via this approach. We are presenting a case of presacral schwannoma in an overweight lady treated by laparoscopic resection. PMID- 27275491 TI - When our body clocks run late: does it make us depressed? PMID- 27275492 TI - Revisiting of cancer vaccine?-Specific immunotherapy comes to field with the biomarker. PMID- 27275490 TI - What does the future hold for immunotherapy in cancer? PMID- 27275493 TI - Vps4A-mediated tumor suppression upon exosome modulation? PMID- 27275494 TI - Standardizing in vitro diagnostics tasks in clinical trials: a call for action. AB - Translational research is defined as the process of applying ideas, insights and discoveries generated through basic scientific inquiry to treatment or prevention of human diseases. Although precise information is lacking, several lines of evidence attest that up to 95% early-phase studies may not translate into tangible outcomes for improving clinical management. Major theoretical hurdles exist in the translational process, but is it also undeniable that many studies may have failed for practical reasons, such as the use of inappropriate diagnostic testing for evaluating efficacy, effectiveness or safety of a given medical intervention, or poor quality in laboratory testing. This can generate biased test results and result in misconceptions during data interpretation, eventually leading to no clinical benefit, possible harm, and a waste of valuable resources. From a genuine economic perspective, it can be estimated that over 10 million euros of funding may be lost each year in clinical trials in the European Union due to preanalytical and analytical problems. These are mostly attributions to the heterogeneity of current guidelines and recommendations for the testing process, to the poor evidence base for basic pre-analytical, analytical and post analytical requirements in clinical trials, and to the failure to thoughtfully integrate the perspectives of clinicians, patients, nurses and diagnostic companies in laboratory best practices. The most rational means for filling the gap between what we know and what we practice in clinical trials cannot discount the development of multidisciplinary teams including research scientists, clinicians, nurses, patients associations and representative of in vitro diagnostic (IVD) companies, who should actively interplay and collaborate with laboratory professionals to adapt and disseminate evidence-based recommendations about biospecimen collection and management into the research settings, from preclinical to phase III studies. PMID- 27275495 TI - Long non-coding RNAs in heart failure: an obvious lnc. AB - Heart failure is a life-threatening and costly ailment characterized by structural and functional impairment of the heart. Despite major advances in understanding protein-mediated transcriptional control and signaling pathways that underlie the cellular and interstitial alterations of heart failure, significant therapeutical breakthroughs for innovative treatments of this disease are still missing. The recent extensive profiling of the mammalian transcriptome has revealed a large number of long non-coding RNAs (lncRNAs) that play a diversity of important regulatory roles in gene expression. In here, we focus on a recent work by Ounzain and colleagues comprising genome-wide profiling of the cardiac transcriptome after myocardial infarction with an emphasis on the identification of novel heart-specific lncRNAs. PMID- 27275496 TI - Focal loss of long non-coding RNA-PRAL, as determinant of cell function and phenotype of hepatocellular carcinoma. PMID- 27275497 TI - From genes to chronotypes: the influence of circadian clock genes on our daily patterns of sleep and wakefulness. PMID- 27275498 TI - TG4010 immunotherapy: a novel weapon against advanced non-small cell lung cancer? PMID- 27275499 TI - Design of nutrition trials in critically ill patients: food for thought. PMID- 27275500 TI - Erratum to Lifestyle changes might prevent Alzheimer's disease. AB - [This corrects the article on p. 222 in vol. 3, PMID: 26488018.]. PMID- 27275501 TI - Erratum to Body fluid biomarkers in Alzheimer's disease. AB - [This corrects the article on p. 70 in vol. 3, PMID: 25992369.]. PMID- 27275502 TI - Erratum to Mitochondrial dysfunction in Kennedy's disease: a new pharmacological target? AB - [This corrects the article on p. 66 in vol. 3, PMID: 25992365.]. PMID- 27275503 TI - Erratum to Rate of early onset Alzheimer's disease: a systematic review and meta analysis. AB - [This corrects the article on p. 38 in vol. 3, PMID: 25815299.]. PMID- 27275504 TI - Letter to the editor regarding the editorial "Quo vadis? - Medical education 2020 between politics and science". PMID- 27275505 TI - Preparation courses for medical clerkships and the final clinical internship in medical education - The Magdeburg Curriculum for Healthcare Competence. AB - BACKGROUND/GOALS: Supporting medical students entering their internships - the clinical clerkship and the internship "final clinical year" (Praktisches Jahr, PJ) - the seminars "Ready for Clerkship" and "Ready for PJ" were held for the first time in 2014 and continued successfully in 2015. These seminars are part of the "Magdeburg Curriculum for Healthcare Competence" (Magdeburger Curriculum zur Versorgungskompetenz, MCV). The concept comprises three main issues: "Understanding interdisciplinary clinical procedures", "Interprofessional collaboration", and "Individual cases and their reference to the system." The aim of the seminar series is to prepare students as medical trainees for their role in the practice-oriented clinical clerkship and PJ, respectively. METHODS: Quality assurance evaluations and didactic research are integral parts of the seminars. In preparation for the "Ready for PJ" seminar a needs assessment was conducted. The seminars were rated by the participants using an anonymized questionnaire consisting of a 5-choice Likert scale (ranging from 1=fully agree to 5=fully disagree) and spaces for comments that was generated by the evaluation software Evasys. RESULTS: The results are presented for the preparatory seminars "Ready for Clerkship" and "Fit fur PJ" held in 2014 and 2015. Overall, the students regarded the facultative courses as very good preparation for the clerkship as well as for the PJ. The three-dimensional main curricular concept of the MCV was recognized in the evaluation as a valuable educational approach. Interprofessional collaboration, taught by instructors focussing in teamwork between disciplines, was scored positively and highly valued. CONCLUSIONS: The "Magdeburg Curriculum for Healthcare Competence" (MCV) integrates clerkship and PJ in a framing educational concept and allows students a better appreciation of their role in patient care and the tasks that they will face. The MCV concept can be utilized in other practice-oriented phases (nursing internship, bed-side teaching, block internships). PMID- 27275506 TI - Simulating the physician as healthcare manager: An innovative course to train for the manager role. AB - INTRODUCTION: During their formal studies medical students acquire extensive medical expertise. However, the medical profession demands additional competencies, such as those involved in efficient resource allocation, business administration, development, organization, and process management in the healthcare system. At present students are not sufficiently prepared for the physician's role as manager. In response, we designed the seminar course, MeCuM SiGma, to impart basic knowledge about healthcare policy and management to students of medicine. This project report describes our teaching strategies and the initial evaluation of this educational project. PROJECT DESCRIPTION: In this semester-long, seminar course introduced in 2010, medical students gather experience with the competencies mentioned above as well as learn basic management skills. The course is offered each winter semester, and students sign up to attend voluntarily; course coordination and organization is done on a voluntary basis by physicians and employees of the Mentoring Office (MeCuM Mentor) at the Medical School of the Ludwig Maximilian University (LMU) in Munich, Germany. The course is open to all students enrolled at the two medical schools in Munich. During the first part of this elective, students learn about the basic principles of the German political and healthcare systems in case based, problem-based tutorials led by trained tutors and in lectures held by experts. In the second part of the course students take on the roles of the University Hospital's executive board of directors and supervisory board to work on an existing hospital project as a group within the scope of a simulation. This phase of the course is accompanied by workshops conducted in cooperation with university-based and off-campus partners that address the procedural learning objectives (teamwork, project management, negotiation strategies, etc.). A suitable, authentic issue currently facing the hospital is selected in advance by the course organizers in coordination with the hospital's executive board. Students then work on this issue in the third and final phase of the course under the supervision of tutors and with assistance from hospital employees. At the end of the course the students formally present the results of their work to the hospital's executive and supervisory boards. RESULTS: The course undergoes written student evaluation, a round of oral feedback, evaluation of the final projects, and feedback from the hospital's executive and supervisory boards. All attendees to date have reported a substantial gain in general knowledge and increased knowledge about the healthcare system, and rate the relevance of the course as being high. The majority felt the content was important for their future practice of medicine. Overall, students evaluated the course very positively [overall rating on a six-point grading scale (1=excellent; 6=unsatisfactory): 1.28 (mean)+/-0.45 (standard deviation)]. DISCUSSION: The importance of the physician's role as manager in medical organizations and as a guiding force in the healthcare system is neglected in medical degree programs. Our seminar course attempts to address this shortcoming, is the object of great interest and receives positive evaluations from seminar participants, our cooperative partners and the executive and supervisory boards of the University Hospital in Munich. PMID- 27275508 TI - Learning Doctor-Patient Communication - Evaluating the effectiveness of the communication training course at Leipzig University from the students' point of view. AB - OBJECTIVE: At the University of Leipzig, the requirements of the Licensing Regulations for Doctors (Approbationsordnung fur Arzte) for the practical training of communication skills are actively implemented by a two-semester communication course. During this course, student tutors impart the basics of interpersonal as well as selected aspects of doctor-patient communication using interactive training methods. This article reports on the effect the training has on the self-assessed communication skills of the medicine students. METHODS: The students' self-perceived communication skills were assessed, both at the beginning and after the completion of the first and second course semesters using questionnaires related to the course's learning goals. Pre-post comparisons were then carried out. 142 students (of 163 students in total) participated in the survey at the start of the course, of which 117 completed the T2-questionnaire at the end of the first course semester. Only the 84 students who also completed the questionnaires in the second course semester were included in the statistical analysis. These responses were analysed using both descriptive and inferential statistics. RESULTS: The comparison of the self-assessments between the four measurement points showed that statistically significant learning progress for all assessed communication skills had taken place from the point of view of the students. The largest changes between measurements, and therefore the greatest learning progress, could be seen in knowledge related skills. CONCLUSION: From the students' point of view the communication training contributes significantly to the acquisition of communication skills. The results suggest that this "hands on" course concept is suited to successfully enhance the students' communication skills. The course concept should therefore be retained for both the course in its current form as well as for any extension of the course into the clinical part of medical school. However, further assessments on the exam results and long term effects should take place. PMID- 27275507 TI - Working as simulated patient has effects on real patient life - Preliminary insights from a qualitative study. AB - BACKGROUND: Persons who simulate patients during medical education understand the routines and the underlying script of medical consultations better. We aimed to explore how simulated patients (SPs) integrated this new understanding into their daily life, how this work affected their private life as patients, and what we can learn from these changes for concepts of empowerment. DESIGN, SETTING, AND PARTICIPANTS: A qualitative interview study. All SPs of Gottingen medical school who had been working longer than three semesters (n=14) were invited and agreed to take part in an open interview about their daily experience with real doctors. Documentary method was used to identify the main issues. Several cases were chosen according to maximum contrast and analysed by in-depth analysis to provide vivid examples of how simulations may affect the real life of the SPs as patients. RESULTS: Our analysis revealed three main changes in the behaviour of SPs as real patients. They were more attentive, had a better understanding of the circumstances under which doctors work, and acted more self-confidently. From the selected cases it became apparent that working as a SP may lead to a constant and significant decrease of fear of hospitals and medical procedures or, in other cases, may enable the SPs to develop new abilities for giving feedback, questioning procedures, and explanations for real doctors. CONCLUSION: working as a simulated patient seems to be well-suited to understand own progression of diseases, to increase self-responsibility and to a confident attitude as patient. PMID- 27275509 TI - An algorithm for calculating exam quality as a basis for performance-based allocation of funds at medical schools. AB - OBJECTIVE: The amendment of the Medical Licensing Act (AAppO) in Germany in 2002 led to the introduction of graded assessments in the clinical part of medical studies. This, in turn, lent new weight to the importance of written tests, even though the minimum requirements for exam quality are sometimes difficult to reach. Introducing exam quality as a criterion for the award of performance-based allocation of funds is expected to steer the attention of faculty members towards more quality and perpetuate higher standards. However, at present there is a lack of suitable algorithms for calculating exam quality. METHODS: In the spring of 2014, the students' dean commissioned the "core group" for curricular improvement at the University Medical Center in Rostock to revise the criteria for the allocation of performance-based funds for teaching. In a first approach, we developed an algorithm that was based on the results of the most common type of exam in medical education, multiple choice tests. It included item difficulty and discrimination, reliability as well as the distribution of grades achieved. RESULTS: This algorithm quantitatively describes exam quality of multiple choice exams. However, it can also be applied to exams involving short assay questions and the OSCE. It thus allows for the quantitation of exam quality in the various subjects and - in analogy to impact factors and third party grants - a ranking among faculty. CONCLUSION: Our algorithm can be applied to all test formats in which item difficulty, the discriminatory power of the individual items, reliability of the exam and the distribution of grades are measured. Even though the content validity of an exam is not considered here, we believe that our algorithm is suitable as a general basis for performance-based allocation of funds. PMID- 27275510 TI - Awareness of ethical issues in medical education: an interactive teach-the teacher course. AB - PURPOSE: We conducted an international, interdisciplinary teach-the-teacher course to sensitize physicians from different countries to ethical issues in medical education. The purpose of this study was to assess the effects of this course. METHOD: Before and after participating in a short session on ethical issues in medical education, 97 physicians from different countries in Africa, Asia, and Europe completed a self-assessment questionnaire on their competence and interest in this field. The short session consisted of working in small groups to identify, analyze and discuss ethical dilemmas described in case vignettes adapted from published examples or written by medical students. In addition to the questionnaire, we conducted a large-group experience to explore four basic orientations of participants in ethical thinking: relativism, intentionalism, consequentialism, and absolutism. RESULTS: We found a significant self-perceived increase in the participants' ability to identify and describe ethical issues and students' dilemmas, in their knowledge about these issues and teaching professionalism, and in their ability to describe both students' perspectives and teachers' and students' behaviors. In addition, participants' feeling of understanding their own culturally learned patterns of determining what is right and wrong increased after taking part in the course. The four contrasting basic ethical orientations showed no significant differences between participants regarding nationality, age, or gender. CONCLUSION: Ethics of education is an important issue for medical teachers. Teachers' self-perceived competence can be increased by working on case vignettes in small groups. PMID- 27275511 TI - An Introduction to the Inverted/Flipped Classroom Model in Education and Advanced Training in Medicine and in the Healthcare Professions. AB - In describing the inverted classroom model (ICM), the following paper is meant to provide an introduction to the subject matter and to serve as a practical guide for those wishing to employ its methods in basic and advanced medical training and education. The ICM is a blended-learning method in which a self-directed learning phase (individual phase) precedes the classroom-instruction phase. During the online phase, factual knowledge is imparted that serves as a basis for the classroom phase. The classroom phase should subsequently be used to assimilate and implement the previously gained knowledge. In contrast, traditional course concepts impart factual knowledge in lectures, for example, or in other face-to-face teaching formats and are followed by the students' self instruction in order to assimilate this knowledge. The goal of the ICM is the shift from passive learning to accelerated learning in order to foster learning at cognitively demanding levels such as analysis, synthesis and evaluation. The concurrent increase in production and use of screencasts and educational videos, the Open Educational Resources "movement" and the widespread use of Massive Open Online Courses (MOOCS) have contributed to the increased dissemination of the inverted-classroom method. The intention of the present paper is to provide an introduction to the subject matter and simultaneously to offer a short overview of important projects and research results in the field of medical education and other health professions. Furthermore, an outline is given of the advantages and disadvantages of the model as well as its potential benefit to the future of medical education and training. PMID- 27275512 TI - Generation of Synthetic Copolymer Libraries by Combinatorial Assembly on Nucleic Acid Templates. AB - Recent advances in nucleic acid-templated copolymerization have expanded the scope of sequence-controlled synthetic copolymers beyond the molecular architectures witnessed in nature. This has enabled the power of molecular evolution to be applied to synthetic copolymer libraries to evolve molecular function ranging from molecular recognition to catalysis. This Review seeks to summarize different approaches available to generate sequence-defined monodispersed synthetic copolymer libraries using nucleic acid-templated polymerization. Key concepts and principles governing nucleic acid-templated polymerization, as well as the fidelity of various copolymerization technologies, will be described. The Review will focus on methods that enable the combinatorial generation of copolymer libraries and their molecular evolution for desired function. PMID- 27275513 TI - Dual Influence of Reduction Annealing on Diffused Hematite/FTO Junction for Enhanced Photoelectrochemical Water Oxidation. AB - Band structure engineering of the interface between the semiconductor and the conductive substrate may profoundly influence charge separation and transport for photovoltaic and photoelectrochemical devices. In this work, we found that a reduction-annealing treatment resulted in a diffused junction through enhanced interdiffusion of hematite/FTO at the interface. The activated hematite exhibited higher nanoelectric conductivity that was probed by a PeakForce TUNA AFM method. Furthermore, charge accumulation and recombination via surface states at the interface were dramatically reduced after the reduction-annealing activation, which was confirmed by transient surface photovoltage measurements. The diffused hematite junction promises improved photoelectrochemical performance without the need for a buffer layer. PMID- 27275514 TI - Antifungal agents and liver toxicity: a complex interaction. AB - INTRODUCTION: The number of antifungal agents has sharply increased in recent decades. Antifungals differ in their spectrum of activity, pharmacokinetic/pharmacodynamic properties, dosing, safety-profiles and costs. Risk of developing antifungal associated hepatotoxicity is multifactorial and is influenced by pre-existing liver disease, chemical properties of the drug, patient demographics, comorbidities, drug-drug interactions, environmental and genetic factors. Antifungal related liver injury typically manifests as elevations in serum aminotransferase levels, although the clinical significance of these biochemical alterations is not always clear. Incidence rates of hepatotoxicity induced by antifungal therapy range widely, occurring most frequently in patients treated with azole antifungals for documented fungal infections. AREAS COVERED: This review provides an update regarding the hepatotoxicity profiles of the modern systemic antifungals used in treatment of invasive fungal infections. Expert commentary: Understanding the likelihood and pattern of hepatotoxicity for all suspected drugs can aid the clinician in early detection of liver injury allowing for intervention and potential mitigation of liver damage. Therapeutic drug monitoring is emerging as a potential tool to assess risk for hepatotoxicity. PMID- 27275515 TI - Synthesis of Glycosyl Amides Using Selenocarboxylates as Traceless Reagents for Amide Bond Formation. AB - Carbohydrate-derived amides were successfully prepared in good yields from a broad range of substrates, including furanosyl and pyranosyl derivatives. The methodology successfully relied on the in situ generation of lithium selenocarboxylates from Se/LiEt3BH and acyl chlorides or carboxylic acids and their reaction with sugar azides. A key aspect of the present protocol is that we start from elemental selenium; isolation and handling of all reactive and sensitive selenium-containing intermediates is avoided, therefore providing the selenocarboxylate the status of a traceless reagent. PMID- 27275516 TI - Sequential Block Copolymer Self-Assemblies Controlled by Metal-Ligand Stoichiometry. AB - While numerous efforts have been devoted to developing easy-to-use probes based on block copolymers for detecting analytes due to their advantages in the fields of self-assembly and sensing, a progressive response on block copolymers in response to a continuing chemical event is not readily achievable. Herein, we report the self-assembly of a 4-piperazinyl-1,8-naphthalimide based functional block copolymer (PS-b-PN), whose self-assembly and photophysics can be controlled by the stoichiometry-dependent metal-ligand interaction upon the side chain. The work takes advantages of (1) stoichiometry-controlled coordination-structural transformation of the piperazinyl moiety on PS-b-PN toward Fe(3+) ions, thereby resulting in a shrinkage-expansion conversion of the self-assembled nanostructures in solution as well as in thin film, and (2) stoichiometry controlled competition between photoinduced electron transfer and spin-orbital coupling process upon naphthalimide fluorophore leading to a boost-decline emission change of the system. Except Fe(3+) ions, such a stoichiometry-dependent returnable property cannot be observed in the presence of other transition ions. The strategy for realizing the dual-channel sequential response on the basis of the progressively alterable nanomorphologies and emissions might provide deeper insights for the further development of advanced polymeric sensors. PMID- 27275517 TI - Ruffling in a Series of Nickel(II) meso-Tetrasubstituted Porphyrins as a Model for the Conserved Ruffling of the Heme of Cytochromes c. PMID- 27275518 TI - Hidden Components in Aqueous "Gold-144" Fractionated by PAGE: High-Resolution Orbitrap ESI-MS Identifies the Gold-102 and Higher All-Aromatic Au-pMBA Cluster Compounds. AB - Experimental and theoretical evidence reveals the resilience and stability of the larger aqueous gold clusters protected with p-mercaptobenzoic acid ligands (pMBA) of composition Aun(pMBA)p or (n, p). The Au144(pMBA)60, (144, 60), or gold-144 aqueous gold cluster is considered special because of its high symmetry, abundance, and icosahedral structure as well as its many potential uses in material and biological sciences. Yet, to this date, direct confirmation of its precise composition and total structure remains elusive. Results presented here from characterization via high-resolution electrospray ionization mass spectrometry on an Orbitrap instrument confirm Au102(pMBA)44 at isotopic resolution. Further, what usually appears as a single band for (144, 60) in electrophoresis (PAGE) is shown to also contain the (130, 50), recently determined to have a truncated-decahedral structure, and a (137, 56) component in addition to the dominant (144, 60) compound of chiral-icosahedral structure. This finding is significant in that it reveals the existence of structures never before observed in all-aromatic water-soluble species while pointing out the path toward elucidation of the thermodynamic control of protected gold nanocrystal formation. PMID- 27275520 TI - Activation of Sigma-1 receptor ameliorates anxiety-like behavior and cognitive impairments in a rat model of post-traumatic stress disorder. AB - Among learning and memory processes, fear memories are crucial in some psychiatric disorders like post-traumatic stress disorder (PTSD). Accumulating evidence shows that the sigma-1 receptor (Sig-1R) has comprehensive involvement in cognitive impairment and neuroprotective effects. It has also been reported that BDNF appears to enhance extinction of fear in anxiety disorders via the MAPK signaling cascade. However, it remains unclear whether BDNF-TrkB-MAPK pathway may be mechanistically involved in the therapeutic effect of sigma-1 receptor in the development of PTSD. To address this question, rats were subjected to a classical single-prolonged stress procedure (SPS) and kept undisturbed for 7 days. After that, rats were re-stressed by re-exposure to the forced swim component of SPS (RSPS). Behavior tests were subsequently performed to assess anxiety and cognitive impairments. Furthermore, we analyzed the expression of BDNF and the phosphorylation of TrkB and three MAPK pathways, namely, the ERK, JNK and p38. We found that the levels of BDNF and p-TrkB were increased following the RSPS procedure, which were reversed by the administration of PRE-084. Meanwhile, among the three MAPK signaling pathways, only the p-ERK expression was increased following the RSPS procedure. Collectively, our results indicate that BDNF-TrkB ERK signaling pathway may be involved in the activation of sigma-1 receptor to yield therapeutic benefits for PTSD. PMID- 27275519 TI - Extinction learning in childhood anxiety disorders, obsessive compulsive disorder and post-traumatic stress disorder: implications for treatment. AB - INTRODUCTION: Threat conditioning and extinction play an important role in anxiety disorders, obsessive compulsive disorder (OCD), and post-traumatic stress disorder (PTSD). Although these conditions commonly affect children, threat conditioning and extinction have been primarily studied in adults. However, differences in phenomenology and neural architecture prohibit the generalization of adult findings to youth. AREAS COVERED: A comprehensive literature search using PubMed and PsycInfo was conducted to identify studies that have used differential conditioning tasks to examine threat acquisition and extinction in youth. The information obtained from this review helps to clarify the influence of these processes on the etiology and treatment of youth with OCD, PTSD and other anxiety disorders. Thirty studies of threat conditioning and extinction were identified Expert commentary: Youth with anxiety disorders, OCD, and PTSD have largely comparable threat acquisition relative to unaffected controls, with some distinctions noted for youth with PTSD or youth who have suffered maltreatment. However, impaired extinction was consistently observed across youth with these disorders and appears to be consistent with deficiencies in inhibitory learning. Incorporating strategies to improve inhibitory learning may improve extinction learning within extinction-based treatments like cognitive behavioral therapy (CBT). Strategies to improve inhibitory learning in CBT are discussed. PMID- 27275521 TI - Elucidating the role of D4 receptors in mediating attributions of salience to incentive stimuli on Pavlovian conditioned approach and conditioned reinforcement paradigms. AB - The power of drug-associated cues to instigate drug 'wanting' and consequently promote drug seeking is a corner stone of contemporary theories of addiction. Gambling disorder has recently been added to the pantheon of addictive disorders due to the phenomenological similarities between the diseases. However, the neurobiological mechanism that may mediate increased sensitivity towards conditioned stimuli in addictive disorders is unclear. We have previously demonstrated using a rodent analogue of a simple slot machine that the dopamine D4 receptor is critically engaged in controlling animals' attribution of salience to stimuli associated with reward in this paradigm, and consequently may represent a target for the treatment of gambling disorder. Here, we investigated the role of acute administration of a D4 receptor agonist on animals' responsivity to conditioned stimuli on both a Pavlovian conditioned approach (autoshaping) and a conditioned reinforcement paradigm. Following training on one of the two tasks, separate cohorts of rats (male and female) were administered a dose of PD168077 shown to be maximally effective at precipitating errors in reward expectancy on the rat slot machine task (10mg/kg). However, augmenting the activity of the D4 receptors in this manner did not alter behaviour on either task. These data therefore provide novel evidence that the D4 receptor does not alter incentive motivation in response to cues on simple behavioural tasks. PMID- 27275527 TI - Clinical significance of residual platelet reactivity in patients treated with platelet P2Y12 inhibitors. AB - Platelet P2Y12 inhibitors have become an essential component of the treatment strategy for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. It is now well-established that approximately 30% of patients treated with the P2Y12 inhibitor clopidogrel display high residual platelet reactivity despite treatment. Patients with high on-treatment platelet reactivity have approximately 2-3-fold greater risk of adverse cardiovascular events and stent thrombosis than those without high platelet reactivity. Conversely, clopidogrel-treated patients with low platelet reactivity display approximately 1.7-fold increased risk of major bleeding. High platelet reactivity is uncommon during treatment with prasugrel and ticagrelor, which achieve a greater reduction in adverse cardiovascular events compared to clopidogrel in ACS patients treated with PCI. This is at the expense of an increase in spontaneous bleeding, however. Minor bleeding events, such as skin haematomas, are more common in prasugrel- and ticagrelor-treated patients that have particularly low platelet reactivity values. These minor bleeding events may occasionally prompt discontinuation of therapy, but their overall prognostic impact is uncertain. However, risk factors for bleeding tend to overlap with risk factors for adverse cardiovascular events. Therefore, patients with these minor bleeding events may also be at higher risk of adverse cardiovascular events, conferring a benefit from low platelet reactivity. Further work is needed to determine the optimal level of platelet reactivity in individuals by taking into account their risk of subsequent adverse cardiovascular events and bleeding. PMID- 27275529 TI - Excitonic Properties of Ordered Metal Nanocluster Arrays: 2D Silver Clusters at Multiporphyrin Templates. AB - The design of ordered arrays of metal nanoclusters such as, for example, two dimensional cluster-organic frameworks might open a new route toward the development of materials with tailored optical properties. Such systems could serve as plasmonically enhanced light-harvesting materials, sensors, or catalysts. We present here a theoretical approach for the simulation of the optical properties of ordered arrays of metal clusters that is based on the ab initio parametrized Frenkel exciton model. We demonstrate that small atomically precise silver clusters can be assembled in one- and two-dimensional arrays on suitably designed porphyrin templates exhibiting remarkable optical properties. By employing explicit time-dependent density functional theory calculations on smaller homologues, we show that the intrinsic optical properties of metal clusters are largely preserved but undergo J- and H-type excitonic coupling that results in controllable splitting of their excited states. Furthermore, ab initio parametrized Frenkel exciton model calculations allow us to predict an energetic splitting of up to 0.77 eV in extended two-dimensional square arrays and 0.79 eV in tilted square aggregates containing up to 25 cluster-porphyrin subunits. PMID- 27275528 TI - Is platelet inhibition correlated with time from last intake on P2Y12 blockers after an acute coronary syndrome? A pilot study. AB - Delay from the last intake of drug could be an important and unexplored variable in the biological response to antiplatelet agents after acute coronary syndrome (ACS) discharge. The objective was to define the impact of the delay from P2Y12 blocker intake on the platelet inhibition level. We compared ticagrelor-, prasugrel-, and clopidogrel-treated patients. All consecutive patients, who had been addressed between 2013 and 2014 for ACS, treated with aspirin and a P2Y12 blocker as maintenance dose, were eligible. One month after discharge, blood sample and a questionnaire were proposed to the patient by a nurse blinded to the protocol. On this questionnaire, three questions about name of the drug, regularity of the intakes, and hour of the last intake were collected. The response to antiplatelet therapy was assessed using platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) and % of adenosine-5' diphosphate-induced aggregation (%ADP).The primary objective of this study was to evaluate the correlation between platelet inhibition and delay from drug intake. We enrolled 474 ACS treated with clopidogrel 75 mg in 182 cases (38% patients), prasugrel in 190 cases (40%), or ticagrelor in 102 patients (22%). We observed a significant correlation between delay from intake and PRI VASP and %ADP for ticagrelor (r = 0.25, p = 0.01; r = 0.21, p = 0.03; respectively). On clopidogrel (r = 0.09, p = 0.24; r = 0.02, p = 0.80; respectively) and prasugrel (r = 0.02, p = 0.82; r = 0.11, p = 0.12 respectively), no correlation exists. In conclusion, ticagrelor, unlike thienopyridines, is associated with a significant correlation between delay from the last intake and platelet inhibition. PMID- 27275530 TI - Evaluation of T1-Weighted MRI to Detect Intratumoral Hemorrhage Within Papillary Renal Cell Carcinoma as a Feature Differentiating From Angiomyolipoma Without Visible Fat. AB - OBJECTIVE: The objective of the present study is to determine whether hemorrhage within papillary renal cell carcinoma (RCC) can be detected using T1-weighted MRI and to ascertain whether it can be used to differentiate papillary RCC from angiomyolipoma (AML) without visible fat. MATERIALS AND METHODS: A retrospective case-control study compared 11 AMLs without visible fat with 58 papillary RCCs smaller than 5 cm that were evaluated using MRI between 2003 and 2015. Two blinded radiologists subjectively evaluated MR images to identify the presence of intratumoral hemorrhage on the basis of a decrease in signal intensity (SI) on in phase, compared with opposed-phase, chemical-shift MRI and also on the basis of the SI of the lesion compared with that of the renal cortex on fat-suppressed T1 weighted MRI. A third radiologist established consensus and measured the ratio of the SI of the lesion to that of the renal cortex (hereafter referred to as the "SI ratio") on T2-weighted MRI; the SI loss index, as calculated using the equation [(SItumorIP - SItumorOP) / SItumorOP] * 100, where IP denotes the in phase image and OP denotes the opposed-phase image; and the SI ratio on fat suppressed T1-weighted MRI. Analyses were performed using tests of association and ROCs. RESULTS: When AMLs without visible fat were compared with papillary RCCs, no statistically significant difference in the T2-weighted SI ratio was noted (p = 0.08). Papillary RCCs had a lower mean (+/- SD) SI loss index (-3.7% +/- 17.3%; range, -51.3% to 31.3%) than did AMLs without visible fat (37.8% +/- 76.1%; range, -15.6% to 184.4%) (p < 0.001). A mean SI loss index of less than 16% resulted in an AUC of 0.71 (95% CI, 0.52-0.91), with a sensitivity and specificity of 22.8% and 100%, respectively, for the diagnosis of papillary RCC. After consensus review, none of the AMLs without visible fat and 16 of the 58 papillary RCCs (27.6%) were found to have a decrease in SI on subjective analysis (p = 0.06, kappa = 0.60). Between groups, no differences were noted in the SI ratio on fat-suppressed T1-weighted MRI (p = 0.58) or in the SI observed on subjective analysis of fat-suppressed T1-weighted MRI (p = 0.20, kappa = 0.48). CONCLUSION: The presence of intratumoral hemorrhage within papillary RCC is a specific feature that differentiates papillary RCCs from AMLs without visible fat. Subjective analysis may be more clinically appropriate than chemical-shift MRI because of limitations in the quantitative measurement of T2* signal with the use of chemical-shift MRI. PMID- 27275531 TI - Neonates and Infants Discharged Home Dependent on Medical Technology: Characteristics and Outcomes. AB - BACKGROUND: Preterm neonates and neonates with complex conditions admitted to a neonatal intensive care unit (NICU) may require medical technology (eg, supplemental oxygen, feeding tubes) for their continued survival at hospital discharge. Medical technology introduces another layer of complexity for parents, including specialized education about neonatal assessment and operation of technology. The transition home presents a challenge for parents and has been linked with greater healthcare utilization. PURPOSE: To determine incidence, characteristics, and healthcare utilization outcomes (emergency room visits, rehospitalizations) of technology-dependent neonates and infants following initial discharge from the hospital. METHODS: This descriptive, correlational study used retrospective medical record review to examine technology-dependent neonates (N = 71) upon discharge home. Study variables included demographic characteristics, hospital length of stay, and type of medical technology used. Analysis of neonates (n = 22) with 1-year postdischarge data was conducted to identify relationships with healthcare utilization. Descriptive and regression analyses were performed. FINDINGS: Approximately 40% of the technology-dependent neonates were between 23 and 26 weeks' gestation, with birth weight of less than 1000 g. Technologies used most frequently were supplemental oxygen (66%) and feeding tubes (46.5%). The mean total hospital length of stay for technology dependent versus nontechnology-dependent neonates was 108.6 and 25.7 days, respectively. Technology-dependent neonates who were female, with a gastrostomy tube, or with longer initial hospital length of stay were at greater risk for rehospitalization. IMPLICATIONS FOR PRACTICE: Assessment and support of families, particularly mothers of technology-dependent neonates following initial hospital discharge, are vital. IMPLICATIONS FOR RESEARCH: Longitudinal studies to determine factors affecting long-term outcomes of technology-dependent infants are needed. PMID- 27275532 TI - Attention and Working Memory in Female Adolescents With Chronic Pain and Pain free Female Adolescents: A Preliminary Pilot Study. AB - OBJECTIVES: Adolescents with chronic pain often report inattention and poor memory. There has been little research on cognitive function in this population. The goal of this preliminary pilot study was to examine differences in cognitive function between adolescents with chronic pain to pain-free adolescents. MATERIALS AND METHODS: All participants completed baseline assessments of pain, school absences, depression, anxiety, and sleep habits. Standardized neurocognitive tests were used to examine cognitive function with a focus on working memory and attention. RESULTS: Recruitment from the chronic pain clinic resulted in a female sample of 13 individuals (largely reflective of the clinical population). Pain-free age-matched and sex-matched individuals (n=12) were therefore also recruited as controls. Individuals with chronic pain had significantly lower working memory scores than controls. Differences were found between groups on the most difficult selective attention task and not on tests of sustained attention, divided attention, or attentional switching. In a stepwise regression with baseline characteristics entered in the first step, pain accounted for approximately 15% of the variance in working memory and medication score counted for 49% of the variance. DISCUSSION: This pilot study is the first study to examine differences in working memory and attention between participants with chronic pain and pain-free adolescents. Our findings suggest that chronic pain may negatively affect adolescents' working memory function and highlights the risk for cognitive difficulties and problems with educational progression in addition to negative health and social effects associated with chronic pain. The study provides a starting point for more research and has the potential to direct better identification and treatment of these cognitive deficits. PMID- 27275533 TI - Cytochrome P450 genes in coronary artery diseases: Codon usage analysis reveals genomic GC adaptation. AB - Establishing codon usage biases are imperative for understanding the etiology of coronary artery diseases (CAD) as well as the genetic factors associated with these diseases. The aim of this study was to evaluate the contribution of 18 responsible cytochrome P450 (CYP) genes for the risk of CAD. Effective number of codon (Nc) showed a negative correlation with both GC3 and synonymous codon usage order (SCUO) suggesting an antagonistic relationship between codon usage and Nc of genes. The dinucleotide analysis revealed that CG and TA dinucleotides have the lowest odds ratio in these genes. Principal component analysis showed that GC composition has a profound effect in separating the genes along the first major axis. Our findings revealed that mutational pressure and natural selection could possibly be the major factors responsible for codon bias in these genes. The study not only offers an insight into the mechanisms of genomic GC adaptation, but also illustrates the complexity of CYP genes in CAD. PMID- 27275534 TI - Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release. PMID- 27275535 TI - Loss of insulin-like growth factor II imprinting is a hallmark associated with enhanced chemo/radiotherapy resistance in cancer stem cells. AB - Insulin-like growth factor II (IGF2) is maternally imprinted in most tissues, but the epigenetic regulation of the gene in cancer stem cells (CSCs) has not been defined. To study the epigenetic mechanisms underlying self-renewal, we isolated CSCs and non-CSCs from colon cancer (HT29, HRT18, HCT116), hepatoma (Hep3B), breast cancer (MCF7) and prostate cancer (ASPC) cell lines. In HT29 and HRT18 cells that show loss of IGF2 imprinting (LOI), IGF2 was biallelically expressed in the isolated CSCs. Surprisingly, we also found loss of IGF2 imprinting in CSCs derived from cell lines HCT116 and ASPC that overall demonstrate maintenance of IGF2 imprinting. Using chromatin conformation capture (3C), we found that intrachromosomal looping between the IGF2 promoters and the imprinting control region (ICR) was abrogated in CSCs, in parallel with loss of IGF2 imprinting in these CSCs. Loss of imprinting led to increased IGF2 expression in CSCs, which have a higher rate of colony formation and greater resistance to chemotherapy and radiotherapy in vitro. These studies demonstrate that IGF2 LOI is a common feature in CSCs, even when the stem cells are derived from a cell line in which the general population of cells maintain IGF2 imprinting. This finding suggests that aberrant IGF2 imprinting may be an intrinsic epigenetic control mechanism that enhances stemness, self-renewal and chemo/radiotherapy resistance in cancer stem cells. PMID- 27275536 TI - Nuclearly translocated insulin-like growth factor 1 receptor phosphorylates histone H3 at tyrosine 41 and induces SNAI2 expression via Brg1 chromatin remodeling protein. AB - The insulin-like growth factor-1 receptor (IGF-1R) is a receptor tyrosine kinase that has crucial roles in cell proliferation and protection from apoptosis. It is therefore not surprising that IGF-1R is often found overexpressed in many types of tumors. This has made IGF-1R a prominent target molecule for pharmacological companies to develop new anti-cancer agents. However, several clinical trials during the last 5 years using IGF-1R specific antibodies have shown disappointing results. We have previously shown that upon IGF-1 stimulation, the receptor becomes SUMOylated and translocates into the nucleus of cancer cells to act as a transcription co-factor. Soon after our original study, several others have reported nuclear IGF-1R (nIGF-1R) as well, and some of them have demonstrated a prognostic value of nIGF-1R expression in cancer. In the current study we demonstrate that nIGF-1R binds to and phosphorylates histone H3 at tyrosine 41 (H3Y41) in HeLa cells. Furthermore, our results suggest that phosphorylation of H3Y41 by nIGF-1R, stabilizes the binding of Brg1 chromatin remodeling protein to Histone H3. Our findings suggest that phosphorylated nIGF-1R, rather than total nIGF-1R, plays a superior role in these contexts. We identified SNAI2 oncogene as a target gene for nIGF-1R and its expression was decreased upon mutation of H3Y41 or by Brg1 knockdown. Furthermore, we demonstrate that both IGF-1R and Brg1 binds to the SNAI2 promoter. As SNAI2 protein is implicated in e.g. cancer invasion and metastasis, the nIGF-1R-mediated effects shown in this study may influence such important tumor phenotypic actions. PMID- 27275537 TI - The HIV-derived protein Vpr52-96 has anti-glioma activity in vitro and in vivo. AB - Patients with actively replicating human immunodeficiency virus (HIV) exhibit adverse reactions even to low irradiation doses. High levels of the virus-encoded viral protein R (Vpr) are believed to be one of the major underlying causes for increased radiosensitivity. As Vpr efficiently crosses the blood-brain barrier and accumulates in astrocytes, we examined its efficacy as a drug for treatment of glioblastoma multiforme (GBM).In vitro, four glioblastoma-derived cell lines with and without methylguanine-DNA methyltransferase (MGMT) overexpression (U251, U87, U251-MGMT, U87-MGMT) were exposed to Vpr, temozolomide (TMZ), conventional photon irradiation (2 to 6 Gy) or to combinations thereof. Vpr showed high rates of acute toxicities with median effective doses of 4.0+/-1.1 MUM and 15.7+/-7.5 MUM for U251 and U87 cells, respectively. Caspase assays revealed Vpr-induced apoptosis in U251, but not in U87 cells. Vpr also efficiently inhibited clonogenic survival in both U251 and U87 cells and acted additively with irradiation. In contrast to TMZ, Vpr acted independently of MGMT expression.Dose escalation in mice (n=12) was feasible and resulted in no evident renal or liver toxicity. Both, irradiation with 3x5 Gy (n=8) and treatment with Vpr (n=5) delayed intracerebral tumor growth and prolonged overall survival compared to untreated animals (n=5; p3x5 Gy<0.001 and pVpr=0.04; log-rank test).Our data show that the HIV-encoded peptide Vpr exhibits all properties of an effective chemotherapeutic drug and may be a useful agent in the treatment of GBM. PMID- 27275538 TI - Post-transcriptional knowledge in pathway analysis increases the accuracy of phenotypes classification. AB - MOTIVATION: Prediction of phenotypes from high-dimensional data is a crucial task in precision biology and medicine. Many technologies employ genomic biomarkers to characterize phenotypes. However, such elements are not sufficient to explain the underlying biology. To improve this, pathway analysis techniques have been proposed. Nevertheless, such methods have shown lack of accuracy in phenotypes classification. RESULTS: Here we propose a novel methodology called MITHrIL (Mirna enrIched paTHway Impact anaLysis) for the analysis of signaling pathways, which extends the work of Tarca et al., 2009. MITHrIL augments pathways with missing regulatory elements, such as microRNAs, and their interactions with genes. The method takes as input the expression values of genes and/or microRNAs and returns a list of pathways sorted according to their degree of deregulation, together with the corresponding statistical significance (p-values). Our analysis shows that MITHrIL outperforms its competitors even in the worst case. In addition, our method is able to correctly classify sets of tumor samples drawn from TCGA. AVAILABILITY: MITHrIL is freely available at the following URL: http://alpha.dmi.unict.it/mithril/. PMID- 27275539 TI - Human induced pluripotent stem cell differentiation and direct transdifferentiation into corneal epithelial-like cells. AB - The corneal epithelium is maintained by a small pool of tissue stem cells located at the limbus. Through certain injuries or diseases this pool of stem cells may get depleted. This leads to visual impairment. Standard treatment options include autologous or allogeneic limbal stem cell (LSC) transplantation, however graft rejection and chronic inflammation lowers the success rate over long time. Induced pluripotent stem (iPS) cells have opened new possibilities for treating various diseases with patient specific cells, eliminating the risk of immune rejection. In recent years, several protocols have been developed, aimed at the differentiation of iPS cells into the corneal epithelial lineage by mimicking the environmental niche of limbal stem cells. However, the risk of teratoma formation associated with the use of iPS cells hinders most applications from lab into clinics. Here we show that the differentiation of iPS cells into corneal epithelial cells results in the expression of corneal epithelial markers showing a successful differentiation, but the process is long and the level of gene expression for the pluripotency markers does not vanish completely. Therefore we set out to determine a direct transdifferentiation approach to circumvent the intermediate state of pluripotency (iPS-stage). The resulting cells, obtained by direct transdifferentiation of fibroblasts into limbal cells, exhibited corneal epithelial cell morphology and expressed corneal epithelial markers. Hence we shows for the first time a direct transdifferentiation of human dermal fibroblasts into the corneal epithelial lineage that may serve as source for corneal epithelial cells for transplantation approaches. PMID- 27275540 TI - GLI1 inhibitor GANT61 exhibits antitumor efficacy in T-cell lymphoma cells through down-regulation of p-STAT3 and SOCS3. AB - T-cell lymphomas are lymphoid malignancies with aggressive clinical course and poor prognosis. Increasing evidences suggest that deregulation of signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) is associated with the pathogenesis of T-cell lymphomas. The hedgehog (Hh)/glioma-associated oncogene-1 (GLI1) pathway, aberrantly activated in a number of tumors, has also been extensively studied. We found that protein expressions of GL11, p-STAT3, STAT3, and SOCS3 were up-regulated in T-cell lymphoma tissues and cell lines. Moreover, the protein expressions of p-STAT3 and SOCS3 were positively correlated with GLI1 in T-cell lymphomas. GLI1 inhibitor GANT61 and lentivirus-mediated siGLI1 exhibited inhibitory effects in the three T cell lines (Jurkat, Karpass299 and Myla3676 cells). The protein expressions of p STAT3 and SOCS3 were decreased accompanied with the inhibition of GLI1. These findings indicated that GANT61 is a promising agent against T-cell lymphoma and the antitumor activity might be partly mediated by down-regulating p-STAT3 and SOCS3. PMID- 27275541 TI - A novel predictive model based on preoperative blood neutrophil-to-lymphocyte ratio for survival prognosis in patients with gastric neuroendocrine neoplasms. AB - PURPOSE: Evaluate the predictive value of the preoperative blood neutrophil-to lymphocyte ratio (NLR) on the clinical outcomes of patients with gastric neuroendocrine neoplasms (g-NENs) after radical surgery. RESULTS: The NLR was significantly higher in patients with g-NENs than in matched normal volunteers (P < 0.05). A higher blood NLR was not significantly associated with clinical characteristics (all P > 0.05). According to the multivariate analysis, the NLR was an independent prognostic factor of RFS and OS. Nomograms, including the NLR, Ki-67 index and lymph node ratio, had superior discriminative abilities to predict clinical outcomes. The recurrence rate was 37% (55/147). The median time to recurrence was 9 months; 48 (87%) patients experienced recurrence within the first 2 years. Both the NLR and Ki-67 index were correlated with liver metastases (both P < 0.05) and were also negatively correlated with recurrence time (both P < 0.05). MATERIALS AND METHODS: We enrolled 147 patients who were diagnosed with g-NENs and underwent radical surgery. Receiver operating characteristic curve analysis was used to identify the optimal value for blood NLR. Univariate and multivariate survival analysis were used to identify prognostic factors for g NENs. A nomogram was adopted to predict RFS and OS after surgery. CONCLUSIONS: As an independent prognostic factor for g-NENs, blood NLR can improve the predictability of RFS and OS. We recommend that g-NEN patients with a high blood NLR or high Ki-67 index undergo surveillance during the first month and then every 3 months for 2 years post-surgery. PMID- 27275542 TI - The reverse-mode NCX1 activity inhibitor KB-R7943 promotes prostate cancer cell death by activating the JNK pathway and blocking autophagic flux. AB - We explored the effects of KB-R7943, an inhibitor of reverse-mode NCX1 activity, in prostate cancer (PCa). NCX1 was overexpressed in PCa tissues and cell lines, and higher NCX1 levels were associated higher PCa grades. At concentrations greater than 10 MUM, KB-R7943 dose-dependently decreased PC3 and LNCaP cell viability. KB-R7943 also increased cell cycle G1/S phase arrest and induced apoptosis in PC3 cells. KB-R7943 increased autophagosome accumulation in PCa cells as indicated by increases in LC3-II levels and eGFP-LC3 puncta. Combined treatment with chloroquine (CQ) and KB-R7943 decreased P62 and increased LC3-II protein levels in PC3 cells, indicating that KB-R7943 blocked autophagic flux. KB R7943 induced autophagosome accumulation mainly by downregulating the PI3K/AKT/m TOR pathway and upregulating the JNK pathway. In xenograft experiments, KB-R7943 inhibited tumor growth. Combined treatment with KB-R7943 and an autophagy inhibitor inhibited growth and increased apoptosis. These results indicate that KB-R7943 promotes cell death in PCa by activating the JNK signaling pathway and blocking autophagic flux. PMID- 27275545 TI - pH driven addressing of silicon nanowires onto Si3N4/SiO2 micro-patterned surfaces. AB - pH was used as the main driving parameter for specifically immobilizing silicon nanowires onto Si3N4 microsquares at the surface of a SiO2 substrate. Different pH values of the coating aqueous solution enabled to experimentally distribute nanowires between silicon nitride and silicon dioxide: at pH 3 nanowires were mainly anchored on Si3N4; they were evenly distributed between SiO2 and Si3N4 at pH 2.8; and they were mainly anchored on SiO2 at pH 2. A theoretical model based on DLVO theory and surface protonation/deprotonation equilibria was used to study how, in adequate pH conditions, Si nanowires could be anchored onto specific regions of a patterned Si3N4/SiO2 surface. Instead of using capillary forces, or hydrophilic/hydrophobic contrast between the two types of materials, the specificity of immobilization could rely on surface electric charge contrasts between Si3N4 and SiO2. This simple and generic method could be used for addressing a large diversity of nano-objects onto patterned substrates. PMID- 27275544 TI - Cancer megafunds with in silico and in vitro validation: accelerating cancer drug discovery via financial engineering without financial crisis. AB - Advances in financial engineering are radically reshaping the biomedical marketplace. For instance, new methods of pooling diversified drug development programs by placing them in a special purpose vehicle (SPV) have been proposed to create a securitized cancer megafund allowing for debt and equity participation. In this study, we perform theoretical and numerical simulations that highlight the role of empirical validation of the projects comprising a cancer megafund. We quantify the degree to which the deliberately designed structure of derivatives and investments is key to its liquidity. Research megafunds with comprehensive in silico and laboratory validation protocols and ability to issue both debt, and equity as well as hybrid financial products may enable conservative investors including pension funds and sovereign government funds to profit from unique securitization opportunities. Thus, while hedging investor's longevity risk, such well-validated megafunds will contribute to health, well being and longevity of the global population. PMID- 27275579 TI - Readmission Rates, Reasons, and Risk Factors in Elderly Patients Treated With Lumbar Fusion for Degenerative Pathology. AB - STUDY DESIGN: Retrospective database review. OBJECTIVE: To determine readmission rates after 1 to 2 level, primary, elective lumbar spinal fusion surgery for degenerative pathology and elucidate risk factors that predict increased risk of 30-day readmission SUMMARY OF BACKGROUND DATA.: Early postoperative readmissions after spine surgery represent a significant source of increased cost and morbidity. As the elderly population represents a demographic with a growing need for spine surgery, readmissions within this population are of significant interest. METHODS: Medicare data (2005-2012) from an insurance database was queried for patients who underwent primary 1 to 2 level posterolateral lumbar spine fusion surgeries for degenerative lumbar pathology. After applying specific exclusion criteria to select for elderly patients (65-84 yr) undergoing mostly elective procedures, 52,567 patients formed the final study population. Readmission rates for medical, surgical, and all reasons were calculated within 30 days, 90 days, and 1 year postoperatively. Risk factors for medical, surgical, and all 30-day readmissions were also determined. RESULTS: Within 30 days, 90 days, and 1 year, 1510 (2.9%), 2776 (5.3%), and 6574 (12.5%) patients were readmitted, respectively. At 30 days, surgical diagnoses constituted 50.1% of all readmissions. Wound infection was the reason for readmission in 25.8% of all readmissions within 30 days. Diagnoses of chronic pulmonary disease (OR 1.41 95% CI 1.22-1.63), obesity (OR 2.20 95% CI 1.90-2.54), and positive smoking history (OR 1.33 95% CI 1.15-1.54) were associated with increased risk of surgical readmission. CONCLUSION: Elderly patients undergoing lumbar spine fusion experience 30-day, 90-day, and 1-year readmission rates of 2.9, 5.3, and 12.5% for both medical and surgical reasons. Surgical site infection and wound complications are the most common surgery-related reasons for readmission. Medical diagnoses are more predominant during later readmissions, highlighting the comorbidity burden present in elderly patients. LEVEL OF EVIDENCE: 4. PMID- 27275580 TI - Development and Implementation of a Capstone Objective Structured Clinical Examination in Nurse Practitioner and Nurse-Midwifery Programs. AB - Determining when advanced practice registered nurse students are safe and competent for beginning-level practice is challenging. This article describes the development and testing of a capstone objective structured clinical examination designed to evaluate the practice readiness of students enrolled in the family, adult-gerontology, women's health nurse practitioner, and nurse-midwifery tracks. Lessons learned from this process and how they were used to enhance the curricula are discussed. PMID- 27275581 TI - Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors. AB - The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27275583 TI - Locally Downscaled and Spatially Customizable Climate Data for Historical and Future Periods for North America. AB - Large volumes of gridded climate data have become available in recent years including interpolated historical data from weather stations and future predictions from general circulation models. These datasets, however, are at various spatial resolutions that need to be converted to scales meaningful for applications such as climate change risk and impact assessments or sample-based ecological research. Extracting climate data for specific locations from large datasets is not a trivial task and typically requires advanced GIS and data management skills. In this study, we developed a software package, ClimateNA, that facilitates this task and provides a user-friendly interface suitable for resource managers and decision makers as well as scientists. The software locally downscales historical and future monthly climate data layers into scale-free point estimates of climate values for the entire North American continent. The software also calculates a large number of biologically relevant climate variables that are usually derived from daily weather data. ClimateNA covers 1) 104 years of historical data (1901-2014) in monthly, annual, decadal and 30-year time steps; 2) three paleoclimatic periods (Last Glacial Maximum, Mid Holocene and Last Millennium); 3) three future periods (2020s, 2050s and 2080s); and 4) annual time-series of model projections for 2011-2100. Multiple general circulation models (GCMs) were included for both paleo and future periods, and two representative concentration pathways (RCP4.5 and 8.5) were chosen for future climate data. PMID- 27275582 TI - The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment. AB - BACKGROUND: Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. METHODS: Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS). RESULTS: High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29-0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014). CONCLUSION: This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers. PMID- 27275584 TI - Location of Tessellations in Ocular Fundus and Their Associations with Optic Disc Tilt, Optic Disc Area, and Axial Length in Young Healthy Eyes. AB - Tessellated fundus is found as common and early-phase characteristic of myopic eyes and their locations are varied among patients. However, the relationship between their locations and morphological parameters of the eyes is still unknown. The purpose is this study is to determine the locations of the tessellations in the ocular fundus of young healthy eyes, and to determine relationships between their locations and morphological parameters of the eyes. This is a prospective observational cross sectional study of 126 eyes of 126 healthy volunteers (mean age 26.0+/-4.1 years). The eyes were classified into eight groups based on the location of the tessellations; no tessellation, temporal, infra-temporal, inferior, nasal, peripapillary, whole retina, and unclassified tessellations. The degree of optic disc tilt was quantified using a sine curve fitting program on the optical coherence tomographic circle scan images. The correlations between each tessellation location and the axial length, area of the optic disc plus conus (AOC), and optic disc tilt were determined. Forty-four eyes were place in the no tessellation group, 12 eyes in the temporal, 21 eyes in the infra-temporal, 9 eyes in the inferior, 8 eyes in the nasal, 15 eyes in the peripapillary, 11 eyes in the whole, and 6 eyes in the unclassified groups. The differences in the axial lengths between the no tessellation group and the infra-temporal groups were significant. A significant difference was found in the AOC between the no tessellation and the inferior, infra-temporal, and peripapilalry groups. A significant difference was found in the optic disc tilt between the no tessellation and infra-temporal groups (P<0.05). The tessellations are located at specific sites in the fundus of young healthy eyes with the infra-temporal location most frequent. It was correlated with some parameters associated with myopia. PMID- 27275586 TI - "I would like to be a surgeon, but ...." Will two years be enough? PMID- 27275585 TI - Post-traumatic stress symptoms in children and adolescents with chronic pain: A topical review of the literature and a proposed framework for future research. AB - BACKGROUND AND OBJECTIVE: The co-occurrence of chronic pain and post-traumatic stress symptoms (PTSS) and post-traumatic stress disorder (PTSD) has gained increasing research attention. Studies on associations among pain and PTSS or PTSD in youth have largely been conducted in the context of acute injury or trauma. Less is known about the risk for co-occurrence with paediatric chronic pain. In this review, we (1) propose a conceptual framework to outline factors salient during childhood that may be associated with symptom severity, co occurrence and mutual maintenance, (2) present relevant literature on PTSS in youth with acute and chronic pain and identify research gaps and (3) provide recommendations to guide paediatric research examining shared symptomatology. DATABASES AND DATA TREATMENT: Electronic databases (PubMed and Google Scholar) were used to identify relevant articles using the search terms 'child, adolescent, paediatric, chronic pain, acute pain, post-traumatic stress symptoms and post-traumatic stress disorder'. Studies were retrieved and reviewed based on relevance to the topic. RESULTS: Our findings revealed that existing biobehavioural and ecological models of paediatric chronic pain lack attention to traumatic events or the potential development of PTSS. Paediatric studies are also limited by lack of a conceptual framework for understanding the prevalence, risk and trajectories of PTSS in youth with chronic pain. CONCLUSIONS: Our new developmentally informed framework highlights individual symptoms and shared contextual factors that are important when examining potential associations among paediatric chronic pain and PTSS. Future studies should consider bidirectional and mutually maintaining associations, which will be aided by prospective, longitudinal designs. WHAT DOES THIS REVIEW ADD?: This review presents relevant literature on pain and PTSS in youth and proposes a conceptual framework to examine factors salient during childhood that may be associated with symptom severity, comorbidity and mutual maintenance of chronic pain and PTSS in paediatric populations. We highlight dynamic factors that may change across children's development and provide recommendations to guide paediatric research examining potential associations among PTSS and chronic pain. PMID- 27275587 TI - Expression of Ki-67 and P16 INK4a in chemically-induced perioral squamous cell carcinomas in mice. AB - OBJECTIVE: to evaluate the influence of Ki-67 and P16INK4a proteins immunohistochemical expressions on the clinical and morphological parameters of perioral squamous cell carcinoma induced with 9,10-dimethyl-1,2-benzanthracene (DMBA) in mice. METHODS: we topically induced the lesions in the oral commissure of ten Swiss mice for 20 weeks, determining the time to tumors onset and the average tumor volume up to 26 weeks. In histopathological analysis, the variables studied were histological malignancy grade and the immunohistochemical expression of Ki-67 and P16INK4a proteins. The correlation between variables was determined by application of the Spearman correlation test. RESULTS: the mean time to onset of perioral lesions was 21.1 +/- 2.13 weeks; mean tumor volume was 555.91 +/- 205.52 mm3. Of the induced tumors, 80% were classified as low score and 20% high score. There was diffuse positivity for Ki-67 in 100% of lesions - Proliferation Index (PI) of 50.1 +/- 18.0. There was a strong direct correlation between Ki-67 immunoreactivity and tumor volume (R = 0.702) and a low correlation with the malignancy score (R = 0.486). The P16INK4a protein expression was heterogeneous, showing a weak correlation with tumor volume (R = 0.334). There was no correlation between the immunohistochemical expression of the two proteins studied. CONCLUSION: in an experimental model of DMBA-induced perioral carcinogenesis, tumor progression was associated with the tumor proliferative fraction (Ki-67 positive cells) and with tumor histological grading, but not with P16INK4a expression. OBJETIVO: avaliar a influencia da expressao imuno histoquimica das proteinas Ki-67 e p16INK4a sobre parametros clinico-morfologicos em carcinomas espinocelulares periorais quimicamente induzidos com 9,10-dimetil 1,2-benzantraceno (DMBA) em modelo murino. METODOS: as lesoes foram induzidas topicamente na comissura labial de dez camundongos Swiss durante 20 semanas, sendo determinado o momento de surgimento dos tumores e volume tumoral medio ate 26 semanas. Na analise histopatologica, as variaveis estudadas foram gradacao histologica de malignidade tumoral e expressao imuno-histoquimica das proteinas Ki-67 e p16INK4a. A correlacao entre as variaveis estudadas foi determinada pela aplicacao do teste de correlacao de Spearman. RESULTADOS: o tempo medio de surgimento das lesoes periorais foi 21,1+/-2,13 semanas. Volume tumoral medio foi de 555,91+/-205,52mm3. Dos tumores produzidos, 80% foram classificados como de baixo escore e 20%, alto escore. Evidenciou-se positividade difusa para Ki-67 em 100% das lesoes - indice de marcacao (PI) de 50,1+/-18,0. Verificou-se correlacao direta forte entre a imunoexpressao do Ki-67 e o volume tumoral (R=0,702) e fraca correlacao com o escore de malignidade (R=0,486). A expressao da proteina p16INK4a foi heterogenea, mostrando fraca correlacao com o volume tumoral (R=0,334). Nao houve correlacao entre a expressao imuno-histoquimica das duas proteinas estudadas. CONCLUSAO: Em modelo experimental de carcinogenese perioral DMBA-induzida, a progressao tumoral esta associada a fracao proliferativa do tumor (celulas ki-67 positivas) e com a gradacao histologica tumoral, porem nao com a expressao da p16INK4a. PMID- 27275588 TI - Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine. AB - OBJECTIVE: to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. METHODS: we divided forty Wistar rats into four groups: group I - control group (Sham); group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. RESULTS: in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000). CONCLUSION: Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones. OBJETIVO: o objetivo deste trabalho e avaliar o efeito da L-lisina nos epitelios vesical e intestinal de ratas submetidas a vesicossigmoidostomia. METODOS: quarenta ratas Wistar, foram divididas em quatro grupos: grupo I- grupo controle (Sham); grupo II- submetido a vesicossigmoidostomia e tratado com L-lisina 150mg/kg; grupo III- submetido apenas a vesicossigmoidostomia; e grupo IV- recebeu L-lisina 150mg/kg. Apos oito semanas os animais foram sacrificados. RESULTADOS: na bexiga de todos os animais operados observou-se hiperplasia simples, papilar e nodular de celulas transicionais, papiloma de celulas transicionais e metaplasia escamosa. Quanto a ocorrencia de focos de criptas aberrantes nos colos dos animais operados, nao foi evidenciado diferenca estatistica significante em nenhum dos fragmentos distal, proximal e medio, e todos juntos (P=1,0000). CONCLUSAO: apesar de, estatisticamente, nao ter havido promocao de carcinogenese nos epitelios dos ratos tratados com L-lisina, no tempo observado, e nitida a histogenese da carcinogenese de bexiga em sua fase inicial, no epitelio vesical, em todos os ratos operados, estando esta provavelmente associada a infeccao cronica e aos diminutos calculos vesicais. PMID- 27275589 TI - The influence of nicotine in healing of small bowel anastomoses in rats: angiogenesis and miofibroblasts. AB - OBJECTIVE: to know the effect of nicotine on angiogenesis and myofibroblast formation in anastomoses of the small bowel of rats. METHODS: we randomly divided 60 Wistar rats into the groups Nicotine (N) and control (C), according to the proposed treatment. Each group was subdivided into three subgroups according to the time interval used for the evaluation (7, 14 or 28 days). The N group with 30 animals received nicotine subcutaneously at a dose of 2mg/kg body weight, diluted in 0.3ml of 0.9% saline, twice daily for 28 days prior to the operation, and for more 7, 14 or 28 days, depending on the subgroup. The C group (also 30 animals) received only saline on the same conditions and time intervals. After 28 days we carried out an end-to-end anastomosis 10cm distal to the duodenojejunal flexure in each rat. After 7, 14 or 28 days after surgery, we euthanized ten animals of each group, sent specimens of the anastomosis areas, 1cm proximal to 1cm distal, to counting of blood vessels and myofibroblasts through immunohistochemical staining by the application of monoclonal anti-factor VIII antibodies and anti smooth muscle alpha-actin. RESULTS: the administration of nicotine led to the decrease in the number of blood vessels measured on the 28th postoperative day and the number of myofibroblasts measured on the seventh day following completion of the anastomoses. CONCLUSION: administration of nicotine was deleterious on angiogenesis and myofibroblast formation in rats' small intestine anastomoses. OBJETIVO: conhecer o efeito da nicotina sobre a angiogenese e formacao de miofibroblastos em anastomoses do intestino delgado de ratos. METODOS: sessenta ratos Wistar foram divididos de maneira aleatoria em grupos Nicotina(N) e Controle (C), conforme o tratamento proposto. Cada grupo foi subdividido em tres subgrupos, de acordo com o intervalo de tempo utilizado para a avaliacao (7, 14 ou 28 dias). O grupo N, com 30 animais, recebeu nicotina por via subcutanea, na dose de 2mg/Kg de peso, diluida em 0,3ml de solucao salina a 0,9%, em duas aplicacoes diarias, durante 28 dias previos a operacao e por mais 7, 14 ou 28 dias, conforme o subgrupo. O grupo C (igualmente com 30 animais) recebeu somente a solucao salina nas mesmas condicoes e intervalos de tempo. Apos 28 dias efetuou se, em cada rato, anastomose termino-terminal a 10cm da flexura duodenojejunal. Apos 7, 14 ou 28 dias da cirurgia, os dez animais de cada subgrupo foram eutanasiados, sendo que as areas anastomosadas, 1cm proximal a 1cm distal, foram encaminhadas para contagem de vasos sanguineos e miofibroblastos, atraves de coloracao imuno-histoquimica por aplicacao dos anticorpos monoclonais antifator VIII e anti-alfa-actina muscular lisa. RESULTADOS: a administracao de nicotina levou a diminuicao do numero de vasos sanguineos aferidos no 28o dia pos operatorio e do numero de miofibroblastos aferidos no setimo dia apos a realizacao das anastomoses. CONCLUSAO: a administracao de nicotina foi deleteria sobre a angiogenese e formacao de miofibroblastos em anastomoses do intestino delgado de ratos. PMID- 27275590 TI - Extended pelvic resections for the treatment of locally advanced and recurrent anal canal and colorectal cancer: technical aspects and morbimortality predictors aftet 24 consecutive cases. AB - OBJECTIVE: to evaluate the profile of morbidity and mortality and its predictors related to extensive pelvic resections, including pelvic exenteration, to optimize the selection of patients and achieve better surgical results. METHODS: we performed 24 major resections for anorectal pelvic malignancy from 2008 to 2015 in the Instituto do Cancer do Ceara. The factors analyzed included age, weight loss, resected organs, total versus posterior exenteration, angiolymphatic and perineural invasion, lymph node metastasis and overall and disease-free survival. RESULTS: the median age was 57 years and the mean follow-up was ten months. Overall morbidity was 45.8%, with five (20.8%) serious complications. There were no deaths in the first 30 postoperative days. The median overall survival was 39.5 months, and disease-free survival, 30.7 months. Concomitant resection of the bladder was an isolated prognostic factor for higher risk of complications (87.5% vs. 26.7%, p = 0.009). Angiolymphatic invasion and lymph node metastasis did not reach significance with respect to disease-free survival. CONCLUSION: treatment of advanced anorectal tumors is challenging, often requiring combined resections, such as cystectomy and sacrectomy, and complex reconstructions. The magnitude of the operation still carries a high morbidity rate, but is a procedure considered safe and feasible, with a low mortality and adequate locoregional tumor control when performed in referral centers. OBJETIVOS: avaliar o perfil de morbimortalidade e seus fatores preditivos relacionados as resseccoes pelvicas extensas, incluindo a exenteracao pelvica, com o intuito de otimizar a selecao dos pacientes e obtencao de melhores resultados cirurgicos. METODOS: foram realizadas 24 grandes resseccoes pelvicas por neoplasia maligna anorretal de 2008 a 2015 no Instituto do Cancer do Ceara. Os fatores analisados incluiram idade, perda de peso, orgao ressecados, exenteracao total versus posterior, invasao angiolinfatica e perineural, metastase linfonodal e sobrevida global e livre de doenca. RESULTADOS: a mediana de idade foi 57 anos e o tempo medio de seguimento foi dez meses. A morbidade global foi 45,8%, com cinco (20,8%) complicacoes graves. Nao houve obito nos primeiros 30 dias de pos-operatorio. A sobrevida global media foi 39,5 meses e a sobrevida livre de doenca foi 30,7 meses. A resseccao concomitante da bexiga foi fator prognostico isolado com maior risco para complicacoes (87,5% vs. 26,7%, p=0.009). Invasao angiolinfatica e metastase linfonodal nao alcancaram significancia com relacao a sobrevida livre de doenca. CONCLUSAO: o tratamento dos tumores anorretais avancados e desafiador, necessitando frequentemente de resseccoes combinadas, como a cistectomia e sacrectomia, alem de reconstrucoes complexas. A magnitude da cirurgia ainda carrega uma elevada taxa de morbidade, porem e um procedimento considerado seguro e factivel, com uma baixa mortalidade e adequado controle locorregional tumoral quando realizado em centros de referencia. PMID- 27275591 TI - Impact of neoadjuvant therapy in downstaging of lower rectal adenocarcinoma and the role of pelvic magnetic resonance in staging. AB - OBJECTIVE: to evaluate the effect of neoadjuvant therapy on the stage (TNM) of patients with rectal adenocarcinoma and validate the use of MRI as a method of determining locoregional stage. METHODS: we conducted a retrospective study of 157 patients with lower rectum adenocarcinoma, whom we divided into two groups: Group 1, 81 patients (52%) who had undergone surgical treatment initially, with the purpose to analyze the accuracy of locoregional staging by pelvic magnetic resonance imaging throug the comparison of radiological findings with pathological ones; Group 2, 76 patients (48%), who had been submitted to neoadjuvant therapy (chemotherapy and radiation) prior to definitive surgical treatment, so as to evaluate its effects on the stage by comparing clinical and radiological findings with pathology. RESULTS: In group 1, the accuracy of determining tumor depth (T) and lymph node involvement (N) was 91.4% and 82.7%, respectively. In group 2, neoadjuvant therapy decreased the T stage, N stage and TNM stage in 51.3%, 21% and 48.4% of cases, respectively. CONCLUSION: neoadjuvant therapy in patients with rectal adenocarcinoma is effective in decreasing disease stage, and pelvic magnetic resonance imaging is effective for locoregional staging. OBJETIVO: avaliar o efeito da terapia neoadjuvante, nos pacientes portadores de adenocarcinoma de reto, sobre o estadio (TNM) e validar o emprego da ressonancia magnetica como metodo de determinacao do estadio locorregional. METODOS: estudo retrospectivo de 157 pacientes com diagnostico de adenocarcinoma de reto baixo, que foram divididos em dois grupos: Grupo 1, 81 pacientes (52%), submetidos ao tratamento cirurgico de principio, cuja finalidade foi analisar a acuracia da determinacao do estadio locorregional pela ressonancia magnetica da pelve, atraves da comparacao entre os achados radiologicos e os achados anatomopatologicos; Grupo 2, 76 pacientes (48%), encaminhados a terapia neoadjuvante (quimioterapia e radioterapia), antes do tratamento cirurgico definitivo, com o intuito de avaliar seus efeitos sobre o estadio, atraves da comparacao dos achados clinico-radiologicos com os anatomopatologicos. RESULTADOS: no grupo 1, a acuracia da determinacao da profundidade da lesao (T) e do comprometimento linfonodal (N), foram de 91,4% e 82,7%, respectivamente. No grupo 2, a terapia neoadjuvante diminuiu o estadio T, estadio N e o estadio TNM em 51,3%, 21% e 48,4% dos casos, respectivamente. CONCLUSAO: a terapia neoadjuvante nos pacientes com adenocarcinoma de reto e efetiva na diminuicao do estadio e a ressonancia magnetica da pelve e eficaz na determinacao do estadio locorregional. PMID- 27275592 TI - The collagen, fibrinogen and thrombin biological adhesive is effective in treating experimental liver injuries. AB - OBJECTIVE: to evaluate the effectiveness of an collagen-based adhesive associated with fibrinogen and thrombin in experimental liver injuries in rats. METHODS: we randomly divided 30 Wistar rats into three groups: A, B and C. All underwent a standard liver traumatic injury. In group A, the lesion was treated with the adhesive; in group B, with conventional, absorbable suture; group C received no treatment. We analyzed the time of hemostasis, mortality, occurrence of adhesions and any histological changes. RESULTS: there was no statistical difference in relation to mortality (p=0.5820). The adhesive treated group showed the lowest hemostasis times (p=0.0573, odds ratio 13.5) and lower incidence of adhesions (p=0.0119). The histological alterations of the Groups A and B were similar, with foreign body granuloma formation separating the adhesive material and the hepatic stroma suture. CONCLUSION: the collagen adhesive associated with fibrinogen and thrombin was effective in treating experimental hepatic injury, providing a lower incidence of adhesions between the liver and surrounding structures. OBJETIVO: avaliar a eficacia de um adesivo a base de colageno associado ao fibrinogenio e trombina, no trauma hepatico experimental em ratos. METODOS: toram incluidos no estudo 30 ratos Wistar, igualmente divididos aleatoriamente em tres grupos: A, B e C. Todos foram submetidos a lesao traumatica hepatica padronizada. No grupo A, a lesao foi tratada com o adesivo, no grupo B, com sutura convencional com fio absorvivel, e no grupo C, nao houve tratamento da lesao. Foram analisados o tempo de hemostasia, mortalidade, ocorrencia de aderencias e eventuais alteracoes histologicas. RESULTADOS: os resultados mostraram que nao houve diferenca estatistica em relacao a mortalidade (p=0,5820). O grupo tratado com adesivo apresentou os menores tempos de hemostasia (p=0,0573 e odds ratio 13,5) e menor ocorrencia de aderencias (p=0,0119). Microscopicamente as alteracoes histologicas dos grupos A e B foram semelhantes, com a formacao de granuloma de corpo estranho separando o material do adesivo e do fio de sutura do estroma hepatico. CONCLUSAO: o adesivo de colageno associado ao fibrinogenio e trombina foi eficaz no tratamento do trauma hepatico experimental, proporcionado menor ocorrencia de aderencias entre o figado e as estruturas vizinhas. PMID- 27275593 TI - Epidemiology and outcome of patients with postoperative abdominal fistula. AB - OBJECTIVE: to present the epidemiological profile, incidence and outcome of patients who developing postoperative abdominal fistula. METHODS: This observational, cross-sectional, prospective study evaluated patients undergoing abdominal surgery. We studied the epidemiological profile, the incidence of postoperative fistulas and their characteristics, the outcome of this complication and the predictors of mortality. RESULTS: The sample consisted of 1,148 patients. The incidence of fistula was 5.5%. There was predominance of biliary fistula (26%), followed by colonic fistulas (22%) and stomach (15%). The average time to onset of fistula was 6.3 days. For closure, the average was 25.6 days. The mortality rate of patients with fistula was 25.4%. Predictors of mortality in patients who developed fistula were age over 60 years, presence of comorbidities, fistula closure time more than 19 days, no spontaneous closure of the fistula, malnutrition, sepsis and need for admission to the Intensive Care Unit. CONCLUSION: abdominal postoperative fistulas are still relatively frequent and associated with significant morbidity and mortality. OBJETIVO: apresentar o perfil epidemiologico, incidencia e desfecho em pacientes que evoluiram com fistula abdominal pos-operatoria. METODOS: trata-se de um estudo prospectivo transversal observacional que avaliou pacientes submetidos a cirurgia abdominal. Foram estudados o perfil epidemiologico, a incidencia das fistulas pos operatorias e suas caracteristicas, desfecho desta complicacaoe fatores preditivos de mortalidade. RESULTADOS: a amostra constou de 1148 pacientes. A incidencia de fistula foi 5,5%. Houve predominancia de fistulas biliares (26%), seguidas de fistulas colonicas (22%) e gastricas (15%). O tempo medio para o surgimento da fistula foi 6,3 dias. Para o fechamento, a media foi 25,6 dias. A taxa de mortalidade dos pacientes com fistula foi 25,4%. Os fatores preditivos de mortalidade nos casos que desenvolveram fistula foram idade maior do que 60 anos, presenca de comorbidades, tempo de fechamento da fistula superior a 19 dias, nao fechamento espontaneo da fistula, desnutricao, sepse e necessidade de admissao em Unidade de Terapia Intensiva. CONCLUSAO: as fistulas pos-operatorias abdominais ainda sao relativamente frequentes e associadas a morbidade e mortalidade significativas. PMID- 27275594 TI - Analysis of electrocautery generated smoke by chromatographic-mass spectrometry. AB - OBJECTIVE: to analyze the chemical components of the smoke from electrocautery from coagulating muscle and liver tissues of pigs. METHODS: we collected smoke produced by electrocautery applied to porcine tissue in previously evacuated bottles, with qualitative and quantitative analysis of the compounds present through the hyphenated technique gas chromatography / mass spectrometry. RESULTS: there was a majority of decanal aldehyde in the fumes from the subcutaneous, muscle and liver tissues. Fumes of subcutaneous and muscular tissues also showed the presence of hexanal and phenol. In the fumes of subcutaneous and liver tissues we also found toluene and limonene and, finally, nonanal smoke was present in the muscle and liver tissues. CONCLUSION: there is increasing evidence showing that smoke from electrocautery used in subcutaneous, muscle and liver tissue is harmful to human health. Thus, there is need to reduce exposure to it or wear masks with filters capable of retaining these particles. OBJETIVO: analisar quimicamente os componentes da fumaca do eletrocauterio, provenientes da coagulacao de tecidos, muscular e hepatico de suino. METODOS: coleta de fumaca produzida por eletrocauterizacao de tecido porcino em frascos previamente evacuados com analise qualitativa e quantitativa dos compostos presentes, atraves de tecnica hifenada, cromatografia a gas/espectrometria de massas. RESULTADOS: houve presenca majoritaria do aldeido decanal nas fumacas provenientes dos tecidos subcutaneo, muscular e hepatico. Fumacas dos tecidos subcutaneo e muscular mostraram tambem a presenca de hexanal e fenol. Nas fumacas dos tecidos subcutaneo e hepatico foram encontrados ainda tolueno e limoneno e, por fim, nonanal estava presente nas fumacas dos tecidos muscular e hepatico. CONCLUSAO: ha numero crescente de evidencias mostrando que fumaca proveniente de eletrocauterizacao de tecidos subcutaneo, muscular e hepatico e nociva a saude de seres humanos. Portanto, ha necessidade de reduzir a exposicao a ela ou usar mascara com filtro capaz de reter essas particulas. PMID- 27275595 TI - Preliminary analysis of hybrid laparoscopic procedure for resection of gastric submucosal tumors. AB - OBJECTIVE: to evaluate the feasibility, safety and benefits of minimally invasive surgery for resection of gastric submucosal tumor (GSMT). METHODS: we conducted a retrospective study of medical records of patients undergoing endoscopy-assisted laparoscopic resection of gastric submucosal tumors (prospectively collected) from 2011 to 2014. We evaluated clinical data, surgical approach, clinicopathological characteristics of the GSMT (size, location, histopathological and immunohistochemical exams), outcome and patients follow-up. RESULTS: we evaluated six patients, 50% male, mean age 52+/-18 years and common symptoms of heartburn and gastric fullness. All patients underwent hybrid procedure without anatomical impairment of the organ. The average length of stay was 3.5 days and the average size of the tumors was 2.0+/-0.8cm, five of them (83%) in the proximal third of the stomach. The surgical specimens pathological and immunohistochemistry examination revealed one case of ectopic pancreas (17%), one grade 2 neuroendocrine tumor (17%), one lipoma (17%), one GIST (17%) and two leiomyomas (32%). There were no episodes of tumor rupture or intraoperative complications and no conversion to open surgery. During the postoperative follow up period, none of the patients had recurrence, metastasis, fistula or stenosis. CONCLUSION: the results showed that endoscopy-assisted laparoscopic resection is feasible and safe for patients with GSMT. Endoscopy proved to be essential in the location of lesions and as intraoperative support, especially when attempting to preserve the pylorus and cardia during surgery. OBJETIVO: avaliar a viabilidade, seguranca e vantagens da cirurgia minimamente invasiva para resseccao de tumores submucosos gastricos (TUSG). METODOS: estudo retrospectivo dos prontuarios de pacientes submetidos a resseccao videolaparoscopica assistida por endoscopia digestiva alta para tumores submucosos gastricos (coletados prospectivamente) de 2011 a 2014. Os fatores avaliados foram dados clinicos, abordagem cirurgica, caracteristicas clinicopatologicas dos TUSG (tamanho, localizacao, exame anatomopatologico e imuno-histoquimico), resultados e acompanhamento dos pacientes. RESULTADOS: foram avaliados seis pacientes, 50% do sexo masculino, com media de idade 52+/-18 anos e sintomas comuns de pirose e plenitude gastrica. Todos os pacientes foram submetidos ao procedimento hibrido e sem comprometimento anatomico do orgao. O tempo medio de internacao foi 3,5 dias e o tamanho medio dos tumores foi 2,0+/-0,8cm, cinco deles (83%) no terco proximal do estomago. Os exames anatomopatologicos e imuno-histoquimicos das pecas cirurgicas demonstraram um caso de pancreas ectopico (17%), um tumor neuroendocrino grau 2 (17%), um lipoma (17%), um GIST (17%) e dois leiomiomas (32%). Nao houve episodios de ruptura do tumor nem complicacoes intraoperatorias e nenhuma conversao para cirurgia aberta. Durante o periodo de acompanhamento pos-operatorio nenhum dos pacientes apresentou recidiva, metastase, fistula ou estenose. CONCLUSAO: os resultados obtidos mostraram que a resseccao laparoscopica assistida por endoscopia e viavel e segura para pacientes com TUSG. A endoscopia mostrou-se fundamental na localizacao das lesoes e suporte intraoperatorio, principalmente na tentativa de preservar a cardia e o piloro durante a cirurgia. PMID- 27275596 TI - Duodenum inclusion in alimentary transit for preventing or correcting nutritional deficiencies resulting from Roux-en-y gastric bypass in obesity treatment. AB - Nutritional and metabolic complications can develop after Roux-en-Y gastric bypass (RYGB) when there is an exaggerated response to the anatomical and functional changes or when there is inadequate nutritional supplementation. Severe malnutrition is rare, but deficiencies of vitamin B12, iron, calcium and thiamin, metabolic bone disease and gallstones are common after RYGB. Shortage of vitamin B12, iron, calcium and also cholelithiasis are caused at least partially by excluding the duodenum and proximal jejunum from food transit. We designed a new procedure, with the maintenance of the duodenum and proximal jejunum in the gastrointestinal transit through interposition of jejunal loop, as a primary operation to prevent such deficiencies or as corrective surgery for severe malnutrition after RYGB with failure in responding to conservative treatment. Complicacoes nutricionais e metabolicas podem se desenvolver apos a derivacao gastrica em Y de Roux (DGYR) quando ha uma resposta exagerada as mudancas anatomicas e funcionais ou quando ha suplementacao nutricional inadequada. A desnutricao grave e rara, mas deficiencias de vitamina B12, ferro, calcio e tiamina, doenca ossea metabolica e calculos biliares sao comuns apos a DGYR. Dessas deficiencias mencionadas, a de vitamina B12, de ferro, de calcio e tambem a colelitiase, sao causadas, ao menos parcialmente, pela exclusao do duodeno e jejuno proximal. Um novo procedimento com a manutencao do duodeno e do jejuno proximal no transito gastrointestinal, mediante interposicao de alca jejunal, foi idealizado como operacao primaria para prevenir essas deficiencias ou como cirurgia corretiva de desnutricao grave apos DGYR com falha na resposta a exaustivas tentativas de tratamento conservador. PMID- 27275597 TI - Correction: Global Role and Burden of Influenza in Pediatric Respiratory Hospitalizations, 1982-2012: A Systematic Analysis. AB - [This corrects the article DOI: 10.1371/journal.pmed.1001977.]. PMID- 27275598 TI - Chiral Allenes via Alkynylogous Mukaiyama Aldol Reaction. AB - Herein we describe the development of a catalytic enantioselective alkynylogous Mukaiyama aldol reaction. The reaction is catalyzed by a newly designed chiral disulfonimide and delivers chiral allenoates in high yields and with excellent regio-, diastereo-, and enantioselectivity. Our process tolerates a broad range of aldehydes in combination with diverse alkynyl-substituted ketene acetals. The reaction products can be readily derivatized to furnish a variety of highly substituted enantiomerically enriched building blocks. PMID- 27275599 TI - Identification of Targets of a New Nutritional Mixture for Osteoarthritis Management Composed by Curcuminoids Extract, Hydrolyzed Collagen and Green Tea Extract. AB - OBJECTIVE: We have previously demonstrated that a mixture of curcuminoids extract, hydrolyzed collagen and green tea extract (COT) inhibited inflammatory and catabolic mediator's synthesis by osteoarthritic human chondrocytes. The objective of this study was to identify new targets of COT using genomic and proteomic approaches. DESIGN: Cartilage specimens were obtained from 12 patients with knee osteoarthritis. Primary human chondrocytes were cultured in monolayer until confluence and then incubated for 24 or 48 hours in the absence or in the presence of human interleukin(IL)-1beta (10-11M) and with or without COT, each compound at the concentration of 4 MUg/ml. Microarray gene expression profiling between control, COT, IL-1beta and COT IL-1beta conditions was performed. Immunoassays were used to confirm the effect of COT at the protein level. RESULTS: More than 4000 genes were differentially expressed between conditions. The key regulated pathways were related to inflammation, cartilage metabolism and angiogenesis. The IL-1beta stimulated chemokine ligand 6, matrix metalloproteinase-13, bone morphogenetic protein-2 and stanniocalcin1 gene expressions and protein productions were down-regulated by COT. COT significantly decreased stanniocalcin1 production in basal condition. Serpin E1 gene expression and protein production were down-regulated by IL-1beta. COT reversed the inhibitory effect of IL-1beta. Serpin E1 gene expression was up-regulated by COT in control condition. CONCLUSION: The COT mixture has beneficial effect on osteoarthritis physiopathology by regulating the synthesis of key catabolic, inflammatory and angiogenesis factors. These findings give a scientific rationale for the use of these natural ingredients in the management of osteoarthritis. PMID- 27275600 TI - Sex Differences in Diabetes Mellitus Mortality Trends in Brazil, 1980-2012. AB - AIMS: To investigate the hypothesis that the change from the female predominance of diabetes mellitus to a standard of equality or even male preponderance can already be observed in Brazilian mortality statistics. METHODS: Data on deaths for which diabetes mellitus was listed as the underlying cause were obtained from the Brazilian Mortality Information System for the years 1980 to 2012. The mortality data were also analyzed according to the multiple causes of death approach from 2001 to 2012. The population data came from the Brazilian Institute of Geography and Statistics. The mortality rates were standardized to the world population. We used a log-linear joinpoint regression to evaluate trends in age standardized mortality rates (ASMR). RESULTS: From 1980 to 2012, we found a marked increment in the diabetes ASMR among Brazilian men and a less sharp increase in the rate among women, with the latter period (2003-2012) showing a slight decrease among women, though it was not statistically significant. CONCLUSIONS: The results of this study suggest that diabetes mellitus in Brazil has changed from a pattern of higher mortality among women compared to men to equality or even male predominance. PMID- 27275602 TI - Formation of Oxazoles from Elusive Gold(I) alpha-Oxocarbenes: A Mechanistic Study. AB - The gold(I) catalyzed reaction between phenylacetylene, pyridine N-oxide and acetonitrile leading, via a putative gold-alpha-oxocarbene intermediate, towards an oxazole product has been investigated. A novel mass spectrometric method called "delayed reactant labeling" is used to track consecutive and parallel reactions. It clearly shows that the intramolecular formation of a pyridine adduct of gold-alpha-oxocarbene is in competition with the formation of the oxazole product. The reaction mechanism most probably corresponds to competition between acetonitrile and pyridine in an almost barrierless reaction with putative gold-alpha-oxocarbene within the solvent cage. The detected ionic species have been characterized by helium tagging infrared photodissociation spectroscopy. PMID- 27275601 TI - Chronic Methamphetamine Effects on Brain Structure and Function in Rats. AB - Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA-induced neurotoxicity. PMID- 27275603 TI - Functional Relationship between Sucrose and a Cariogenic Biofilm Formation. AB - Sucrose is an important dietary factor in cariogenic biofilm formation and subsequent initiation of dental caries. This study investigated the functional relationships between sucrose concentration and Streptococcus mutans adherence and biofilm formation. Changes in morphological characteristics of the biofilms with increasing sucrose concentration were also evaluated. S. mutans biofilms were formed on saliva-coated hydroxyapatite discs in culture medium containing 0, 0.05, 0.1, 0.5, 1, 2, 5, 10, 20, or 40% (w/v) sucrose. The adherence (in 4-hour biofilms) and biofilm composition (in 46-hour biofilms) of the biofilms were analyzed using microbiological, biochemical, laser scanning confocal fluorescence microscopic, and scanning electron microscopic methods. To determine the relationships, 2nd order polynomial curve fitting was performed. In this study, the influence of sucrose on bacterial adhesion, biofilm composition (dry weight, bacterial counts, and water-insoluble extracellular polysaccharide (EPS) content), and acidogenicity followed a 2nd order polynomial curve with concentration dependence, and the maximum effective concentrations (MECs) of sucrose ranged from 0.45 to 2.4%. The bacterial and EPS bio-volume and thickness in the biofilms also gradually increased and then decreased as sucrose concentration increased. Furthermore, the size and shape of the micro-colonies of the biofilms depended on the sucrose concentration. Around the MECs, the micro colonies were bigger and more homogeneous than those at 0 and 40%, and were surrounded by enough EPSs to support their structure. These results suggest that the relationship between sucrose concentration and cariogenic biofilm formation in the oral cavity could be described by a functional relationship. PMID- 27275604 TI - Utilization of Electrochromically Luminescent Transition-Metal Complexes for Erasable Information Recording and Temperature-Related Information Protection. AB - Transition metal complexes containing pyrazinium or pyridinium moieties display reversible luminescence changes in response to electrical stimuli, which is useful in the development of erasable information recording electric devices. These complexes are also suitable for temperature-related information protection, since chemically-induced luminescence turn-on is temperature-dependent. PMID- 27275605 TI - Acclimatization of Photosynthetic Apparatus of Tor Grass (Brachypodium pinnatum) during Expansion. AB - The aim of this study was to understand the acclimatization mechanisms of photosynthetic apparatus in Brachypodium pinnatum (L.) P. Beauv grass during its expansion. Twelve populations differentiated by age: young (30-50 years old), intermediate age (ca. 100 y) and old (>300 y) were studied. It was confirmed that the decrease of the number of genotypes as a result of environmental stress and competition were reflected in changes in chlorophyll fluorescence (ChlF) parameters. The old stands were dominated by a few genotypes which seem to be the best acclimatized to the self-shading/competition by lowering their photosynthetic performance during light-phase of photosynthesis. On the other hand, the 'high-speed' photosynthetic rate observed in the young populations can be seen as acclimatization to very adverse conditions. Our results clearly confirm that ChlF is a powerful method of inferring physiological mechanisms of the expansion of tor grass. The Principal Component and Redundancy Analyses, followed with k-means classification, allowed to find the differentiation of groups of distinct ChlF parameters and enabled us to relate them to changes in genotypic diversity of populations. We conclude that the plastic morphological and physiological response to changeable habitat light conditions with its optimum in half-shade refers to its forest-steppe origin. PMID- 27275606 TI - Lipopolysaccharide Biosynthesis Genes of Yersinia pseudotuberculosis Promote Resistance to Antimicrobial Chemokines. AB - Antimicrobial chemokines (AMCs) are a recently described family of host defense peptides that play an important role in protecting a wide variety of organisms from bacterial infection. Very little is known about the bacterial targets of AMCs or factors that influence bacterial susceptibility to AMCs. In an effort to understand how bacterial pathogens resist killing by AMCs, we screened Yersinia pseudotuberculosis transposon mutants for those with increased binding to the AMCs CCL28 and CCL25. Mutants exhibiting increased binding to AMCs were subjected to AMC killing assays, which revealed their increased sensitivity to chemokine mediated cell death. The majority of the mutants exhibiting increased binding to AMCs contained transposon insertions in genes related to lipopolysaccharide biosynthesis. A particularly strong effect on susceptibility to AMC mediated killing was observed by disruption of the hldD/waaF/waaC operon, necessary for ADP-L-glycero-D-manno-heptose synthesis and a complete lipopolysaccharide core oligosaccharide. Periodate oxidation of surface carbohydrates also enhanced AMC binding, whereas enzymatic removal of surface proteins significantly reduced binding. These results suggest that the structure of Y. pseudotuberculosis LPS greatly affects the antimicrobial activity of AMCs by shielding a protein ligand on the bacterial cell surface. PMID- 27275607 TI - Oral Tori in Chronic Peritoneal Dialysis Patients. AB - BACKGROUND: The pathogenesis of oral tori has long been debated and is thought to be the product of both genetic and environmental factors, including occlusal forces. Another proposed mechanism for oral tori is the combination of biomechanical forces, particularly in the oral cavity, combined with cortical bone loss and trabecular expansion, as one might see in the early stages of primary hyperparathyroidism. This study investigated the epidemiology of torus palatinus (TP) and torus mandibularis (TM) in peritoneal dialysis patients, and analyzed the influences of hyperparathyroidism on the formation of oral tori. METHOD: In total, 134 peritoneal dialysis patients were recruited between July 1 and December 31, 2015 for dental examinations for this study. Patients were categorized into two subgroups based on the presence or absence of oral tori. Demographic, hematological, biochemical, and dialysis-related data were obtained for analysis. RESULTS: The prevalence of oral tori in our sample group was high at 42.5% (57 of 134), and most patients with oral tori were female (61.4%). The most common location of tori was TP (80.7%), followed by TP and TM (14.0%), then TM (5.3%). All 54 TP cases were at the midline, and most were <2 cm (59.3%), flat (53.7%), and located in the premolar region (40.7%). Of the 11 TM cases, all were bilateral and symmetric, mostly <2 cm (81.9%), lobular (45.4%), and located at premolar region (63.6%). Interestingly, patients with oral tori had slightly lower serum levels of intact parathyroid hormones than those without oral tori, but the difference was not statistically significant (317.3+/-292.0 versus 430.1+/-492.6 pg/mL, P = 0.126). In addition, patients with oral tori did not differ from patients without tori in inflammatory variables such as serum high sensitivity C-reactive protein levels (6.6+/-8.2 versus 10.3+/-20.2 mg/L, P = 0.147) or nutritional variables such as serum albumin levels (3.79+/-0.38 versus 3.77+/-0.45 g/dL, P = 0.790). Furthermore, there were no differences between patients with and without oral tori in dialysis adequacy (weekly Kt/Vurea, 2.14+/ 0.39 versus 2.11+/-0.33, P = 0.533; weekly creatinine clearance rate, 59.31+/ 17.58 versus 58.57+/-13.20 L/1.73 m2, P = 0.781), or peritoneal membrane transporter characteristics (P = 0.098). CONCLUSION: Secondary hyperparathyroidism does not contribute to the formation of tori in peritoneal dialysis patients. Further studies are warranted. PMID- 27275608 TI - In Vitro Interactions between Non-Steroidal Anti-Inflammatory Drugs and Antifungal Agents against Planktonic and Biofilm Forms of Trichosporon asahii. AB - Increasing drug resistance has brought enormous challenges to the management of Trichosporon spp. infections. The in vitro antifungal activities of non-steroidal anti-inflammatory drugs (NSAIDs) against Candida spp. and Cryptococcus spp. were recently discovered. In the present study, the in vitro interactions between three NSAIDs (aspirin, ibuprofen and diclofenac sodium) and commonly used antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin and amphotericin B) against planktonic and biofilm cells of T. asahii were evaluated using the checkerboard microdilution method. The spectrophotometric method and the XTT reduction assay were used to generate data on biofilm cells. The fractional inhibitory concentration index (FICI) and the DeltaE model were compared to interpret drug interactions. Using the FICI, the highest percentages of synergistic effects against planktonic cells (86.67%) and biofilm cells (73.33%) were found for amphotericin B/ibuprofen, and caspofungin/ibuprofen showed appreciable percentages (73.33% for planktonic form and 60.00% for biofilm) as well. We did not observe antagonism. The DeltaE model gave consistent results with FICI (86.67%). Our findings suggest that amphotericin B/ibuprofen and caspofungin/ibuprofen combinations have potential effects against T. asahii. Further in vivo and animal studies to investigate associated mechanisms need to be conducted. PMID- 27275609 TI - Schizophrenia in the Netherlands: Continuity of Care with Better Quality of Care for Less Medical Costs. AB - BACKGROUND: Patients with schizophrenia need continuous elective medical care which includes psychiatric treatment, antipsychotic medication and somatic health care. The objective of this study is to assess whether continuous elective psychiatric is associated with less health care costs due to less inpatient treatment. METHODS: Data concerning antipsychotic medication and psychiatric and somatic health care of patients with schizophrenia in the claims data of Agis Health Insurance were collected over 2008-2011 in the Netherlands. Included were 7,392 patients under 70 years of age with schizophrenia in 2008, insured during the whole period. We assessed the relationship between continuous elective psychiatric care and the outcome measures: acute treatment events, psychiatric hospitalization, somatic care and health care costs. RESULTS: Continuous elective psychiatric care was accessed by 73% of the patients during the entire three year follow-up period. These patients received mostly outpatient care and accessed more somatic care, at a total cost of ?36,485 in three years, than those without continuous care. In the groups accessing fewer or no years of elective care 34% 68% had inpatient care and acute treatment events, while accessing less somatic care at average total costs of medical care from ?33,284 to ?64,509. CONCLUSIONS: Continuous elective mental and somatic care for 73% of the patients with schizophrenia showed better quality of care at lower costs. Providing continuous elective care to the remaining patients may improve health while reducing acute illness episodes. PMID- 27275610 TI - Fixed Erythema on the Abdomen in a Hematologic Patient. PMID- 27275611 TI - On gardens, brackets and money. PMID- 27275612 TI - Should deciduous teeth be preserved in adult patients? How about stem cells? Is it reasonable to preserve them? AB - When seeking orthodontic treatment, many adolescents and adult patients present with deciduous teeth. Naturally, deciduous teeth will inevitably undergo exfoliation at the expected time or at a later time. Apoptosis is the biological trigger of root resorption. In adult patients, deciduous teeth should not be preserved, as they promote: infraocclusion, traumatic occlusion, occlusal trauma, diastemata and size as well as morphology discrepancy malocclusion. Orthodontic movement speeds root resorption up, and so do restoring or recontouring deciduous teeth in order to establish esthetics and function. Deciduous teeth cells are dying as a result of apoptosis, and their regeneration potential, which allows them to act as stem cells, is limited. On the contrary, adult teeth cells have a greater proliferative potential. All kinds of stem cell therapies are laboratory investigative non authorized trials. PMID- 27275613 TI - Bonding brackets on white spot lesions pretreated by means of two methods. AB - OBJECTIVE: The aim of this study was to evaluate the shear bond strength (SBS) of brackets bonded to demineralized enamel pretreated with low viscosity Icon Infiltrant resin (DMG) and glass ionomer cement (Clinpro XT Varnish, 3M Unitek) with and without aging. METHODS: A total of 75 bovine enamel specimens were allocated into five groups (n = 15). Group 1 was the control group in which the enamel surface was not demineralized. In the other four groups, the surfaces were submitted to cariogenic challenge and white spot lesions were treated. Groups 2 and 3 were treated with Icon Infiltrant resin; Groups 4 and 5, with Clinpro XT Varnish. After treatment, Groups 3 and 5 were artificially aged. Brackets were bonded with Transbond XT adhesive system and SBS was evaluated by means of a universal testing machine. Statistical analysis was performed by one-way analysis of variance followed by Tukey post-hoc test. RESULTS: All groups tested presented shear bond strengths similar to or higher than the control group. Specimens of Group 4 had significantly higher shear bond strength values (p < 0.05) than the others. CONCLUSION: Pretreatment of white spot lesions, with or without aging, did not decrease the SBS of brackets. PMID- 27275614 TI - Effect of supplementary zinc on orthodontic tooth movement in a rat model. AB - INTRODUCTION: Osteoclasts and osteoblasts are responsible for regulating bone homeostasis during which the trace element zinc has been shown to exert a cumulative effect on bone mass by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. OBJECTIVE: The aim of the present study was to investigate the effects of zinc (Zn) on orthodontic tooth movement (OTM) in a rat model. MATERIAL AND METHODS: A total of 44 male Wistar rats were divided into four groups of 11 animals each and received 0, 1.5, 20 and 50 ppm Zn in distilled water for 60 days. In the last 21 days of the study, nickel-titanium closed coil springs were ligated between maxillary right incisors and first molars of all rats, and tooth movement was measured at the end of this period. Histological analysis of hematoxylin/eosin slides was performed to assess root resorption lacunae, osteoclast number and periodontal ligament (PDL) width. RESULTS: Mean OTM was calculated as 51.8, 49.1, 35.5 and 45 um in the 0, 1.5, 20 and 50 ppm zinc-receiving groups, respectively. There were no significant differences in neither OTM nor histological parameters among the study groups (p > 0.05). CONCLUSION: According to the results obtained in the current investigation, increase in supplementary zinc up to 50 ppm does not affect the rate of OTM neither bone and root resorption in rats. PMID- 27275615 TI - Comparison of arch forms between Turkish and North American. AB - OBJECTIVE: The aim of this study was to clarify the morphological differences in the mandibular arches of Turkish and North American white subjects. METHODS: The sample included 132 Turkish (34 Class I, 58 Class II, and 40 Class III) and 160 North American (60 Class I, 50 Class II, and 50 Class III) subjects. The most facial portion of 13 proximal contact areas was digitized from photocopied images of patients' mandibular dental arches. Clinical bracket points were calculated for each tooth based on mandibular tooth thickness data. Four linear and two proportional measurements were taken. The subjects were grouped according to arch form types (tapered, ovoid and square) in order to have frequency distribution compared between ethnic groups in each Angle classification. RESULTS: The Turkish group showed significantly lower molar depth and more significant molar width depth (W/D) ratio in all three Angle classifications. On the other hand, the Turkish group also showed a significantly larger intercanine width in Class III malocclusion and intermolar width in Class II malocclusion. The most frequent arch forms seen were the ovoid arch form in the Turkish group and the tapered form in the white group. CONCLUSIONS: Our results demonstrate that when treating Turkish patients, one should expect to use preformed ovoid arch form orthodontic wires in a significant percentage of patients. PMID- 27275616 TI - Self-esteem in adolescents with Angle Class I, II and III malocclusion in a Peruvian sample. AB - OBJECTIVE: To compare self-esteem scores in 12 to 16-year-old adolescents with different Angle malocclusion types in a Peruvian sample. MATERIAL AND METHODS: A cross-sectional study was conducted in a sample of 276 adolescents (159, 52 and 65 with Angle Class I, II and III malocclusions, respectively) from Trujillo, Peru. Participants were asked to complete the Rosenberg Self-Esteem Scale (RSES) and were also clinically examined, so as to have Angle malocclusion classification determined. Analysis of covariance (ANCOVA) was used to compare RSES scores among adolescents with Class I, II and III malocclusions, with participants' demographic factors being controlled. RESULTS: Mean RSES scores for adolescents with Class I, II and III malocclusions were 20.47 +/- 3.96, 21.96 +/- 3.27 and 21.26 +/- 4.81, respectively. The ANCOVA test showed that adolescents with Class II malocclusion had a significantly higher RSES score than those with Class I malocclusion, but there were no differences between other malocclusion groups. Supplemental analysis suggested that only those with Class II, Division 2 malocclusion might have greater self-esteem when compared to adolescents with Class I malocclusion. CONCLUSION: This study shows that, in general, self-esteem did not vary according to adolescents' malocclusion in the sample studied. Surprisingly, only adolescents with Class II malocclusion, particularly Class II, Division 2, reported better self-esteem than those with Class I malocclusion. A more detailed analysis assessing the impact of anterior occlusal features should be conducted. PMID- 27275617 TI - The effect of canine disimpaction performed with temporary anchorage devices (TADs) before comprehensive orthodontic treatment to avoid root resorption of adjacent teeth. AB - OBJECTIVE: The aim of this study was to evaluate the movement of impacted canines away from the roots of neighboring teeth before full-mouth bracket placement, performed by means of TADs to decrease undesired side effects on adjacent teeth. METHODS: The study sample consisted of 34 palatally impacted canines, being 19 in the experimental group and 15 in the control group. In the experimental group, before placement of brackets, the impacted canine was erupted by means of miniscrews. In the control group, after initiation of comprehensive orthodontics, canine disimpaction was performed by means of a cantilever spring soldered to a palatal bar. At the end of treatment, volume of lateral incisors and canine root resorption were measured and compared by means of a CBCT-derived tridimensional model. Visual Analogue Scale (VAS) score, bleeding on probing (BOP) and gingival index (GI) were recorded. Clinical success rate was also calculated. RESULTS: The volume of root resorption of lateral teeth in the control group was significantly greater than in the experimental group (p < 0.001). At the end of treatment, VAS score, GI and BOP were not significantly different between the two groups. CONCLUSION: Based on our results, it seems that disimpaction of canines and moving them to the arch can be done successfully carried out with minimal side effects by means of skeletal anchorage. PMID- 27275618 TI - Peri-implant evaluation of osseointegrated implants subjected to orthodontic forces: results after three years of functional loading. AB - OBJECTIVE: The objective of this study was to clinically and radiographically assess the peri-implant conditions of implants used as orthodontic anchorage. METHODS: Two groups were studied: 1) a test group in which osseointegrated implants were used as orthodontic anchorage, with the application of 200-cN force; and 2) a control group in which implants were not subjected to orthodontic force, but supported a screw-retained prosthesis. Clinical evaluations were performed three, six and nine months after prosthesis installation and 1- and 3 year follow-up examinations. Intraoral periapical radiographs were obtained 30 days after surgical implant placement, at the time of prosthesis installation, and one, two and three years thereafter. The results were compared by Kruskal Wallis test. RESULTS: There was no statistically significant difference in clinical probing depth (p = 0.1078) or mesial and distal crestal bone resorption (p = 0.1832) during the study period. After three years of follow-up, the mean probing depth was 2.21 mm for the control group and 2.39 mm for the test group. The implants of the control group showed a mean distance between the bone crest and implant shoulder of 2.39 mm, whereas the implants used as orthodontic anchorage showed a mean distance of 2.58 mm at the distal site. CONCLUSION: Results suggest that the use of stable intraoral orthodontic anchorage did not compromise the health of peri-implant tissues or the longevity of the implant. PMID- 27275619 TI - Translucency and color match with a shade guide of esthetic brackets with the aid of a spectroradiometer. AB - OBJECTIVE: Since the color of esthetic brackets should match that of teeth, the aims of this study were to determine the color and translucency of esthetic brackets by means of the clinically relevant use of a spectroradiometer, and to compare the color of brackets with that of a commercial shade guide. METHODS: The color of central and tie-wing regions of four plastic and four ceramic brackets was measured according to the CIE L*a*b* color scale over white and black backgrounds. Brackets were classified into five groups based on their composition. The color of Vitapan Classical Shade Guide tabs was also measured. Translucency parameter (TP) and contrast ratio (CR) were calculated to determine translucency. RESULTS: Color differences between brackets and the shade guide tabs were 10.4 - 34.5 ?E*ab units. TP and CR values for the central region were 16.4 - 27.7 and 0.38 - 0.58, whereas for the tie-wings they were 24.0 - 39.9 and 0.25 - 0.45, respectively. The color coordinates, TP and CR values were significantly influenced by bracket composition and brand (p < 0.05). CONCLUSIONS: Esthetic brackets investigated herein showed unacceptable color differences (?E*ab > 5.5) compared with the shade guide tabs. Differences in the translucency of brackets by brand were within the visually perceptible range (?CR > 0.07). Therefore, brackets showing the best matching performance for each case should be selected considering esthetic and functional demands. PMID- 27275620 TI - Orthodontic treatment outcomes obtained by application of a finishing protocol. AB - OBJECTIVE: To evaluate the results of a finishing protocol implemented in patients treated in the Orthodontics graduate program at Universidad de Antioquia. Evaluation was carried out by means of the criteria set by the Objective Grading System (OGS) of the American Board of Orthodontics (ABO). METHODS: Cast models and panoramic radiographs of 34 patients were evaluated. The intervention group (IG) consisted of 17 patients (19.88 +/- 4.4 years old) treated under a finishing protocol. This protocol included training in finishing, application of a finishing guide, brackets repositioning and patient's follow-up. Results of the IG were compared to a control group of 17 patients (21.88 +/- 7.0 years old) selected by stratified randomization without finishing intervention (CG). RESULTS: The scores for both CG and IG were 38.00 +/- 9.0 and 31.41 +/- 9.6 (p = 0.048), respectively. The score improved significantly in the IG group, mainly regarding marginal ridges (CG: 5.59 +/- 2.2; IG: 3.65 +/- 1.8) (p = 0.009) and root angulation (CG: 7.59 +/- 2.8; IG: 4.88 +/- 2.6) (p = 0.007). Criteria that did not improve, but had the highest scores were: alignment (CG: 6.35 +/- 2.7; IG: 6.82 +/- 2.8) (p = 0.62) and buccolingual inclination (CG: 3.6 +/- 5.88; IG: 5.29 +/- 3.9) (p = 0.65). CONCLUSIONS: Standardization and implementation of a finishing protocol contributed to improve clinical performance in the Orthodontics graduate program, as expressed by occlusal outcomes. Greater emphasis should be given on the finishing phase to achieve lower scores in the ABO grading system. PMID- 27275622 TI - Angle Class I malocclusion with anterior negative overjet. AB - This clinical case report describes the orthodontic treatment of an 8-year and 9 month old female patient with Angle Class I malocclusion, anterior crossbite and canine Class III relationship. Orthodontic treatment was carried out in two stages. The first one was orthopedic, while the second one included the use of a fixed appliance and the need for space gain for reshaping of maxillary lateral incisors. The two-stage treatment combined with multidisciplinary Restorative Cosmetic Dentistry allowed excellent esthetic and functional outcomes to be achieved. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as a requirement for the title of certified by the BBO. PMID- 27275621 TI - Changes in alveolar bone support induced by the Herbst appliance: a tomographic evaluation. AB - OBJECTIVE: This study evaluated alveolar bone loss around mandibular incisors, induced by the Herbst appliance. METHODS: The sample consisted of 23 patients (11 men, 12 women; mean age of 15.76 +/- 1.75 years), Class II, Division 1 malocclusion, treated with the Herbst appliance. CBCT scans were obtained before treatment (T0) and after Herbst treatment (T1). Vertical alveolar bone level and alveolar bone thickness of mandibular incisors were assessed. Buccal (B), lingual (L) and total (T) bone thicknesses were assessed at crestal (1), midroot (2) and apical (3) levels of mandibular incisors. Student's t-test and Wilcoxon t-test were used to compare dependent samples in parametric and nonparametric cases, respectively. Pearson's and Spearman's rank correlation analyses were performed to determine the relationship of changes in alveolar bone thickness. Results were considered at a significance level of 5%. RESULTS: Mandibular incisors showed no statistical significance for vertical alveolar bone level. Alveolar bone thickness of mandibular incisors significantly reduced after treatment at B1, B2, B3, T1 and significantly increased at L2. The magnitude of the statistically significant changes was less than 0.2 mm. The changes in alveolar bone thickness showed no statistical significance with incisor inclination degree. CONCLUSIONS: CBCT scans showed an association between the Herbst appliance and alveolar bone loss on the buccal surface of mandibular incisors; however, without clinical significance. PMID- 27275623 TI - Understanding the basis of space closure in Orthodontics for a more efficient orthodontic treatment. AB - INTRODUCTION: Space closure is one of the most challenging processes in Orthodontics and requires a solid comprehension of biomechanics in order to avoid undesirable side effects. Understanding the biomechanical basis of space closure better enables clinicians to determine anchorage and treatment options. In spite of the variety of appliance designs, space closure can be performed by means of friction or frictionless mechanics, and each technique has its advantages and disadvantages. Friction mechanics or sliding mechanics is attractive because of its simplicity; the space site is closed by means of elastics or coil springs to provide force, and the brackets slide on the orthodontic archwire. On the other hand, frictionless mechanics uses loop bends to generate force to close the space site, allowing differential moments in the active and reactive units, leading to a less or more anchorage control, depending on the situation. OBJECTIVE: This article will discuss various theoretical aspects and methods of space closure based on biomechanical concepts. PMID- 27275624 TI - Dynamic self-organization of microwell-aggregated cellular mixtures. AB - Cells with different cohesive properties self-assemble in a spatiotemporal and context-dependent manner. Previous studies on cell self-organization mainly focused on the spontaneous structural development within a short period of time during which the cell numbers remained constant. However the effect of cell proliferation over time on the self-organization of cells is largely unexplored. Here, we studied the spatiotemporal dynamics of self-organization of a co-culture of MDA-MB-231 and MCF10A cells seeded in a well defined space (i.e. non-adherent microfabricated wells). When cell-growth was chemically inhibited, high cohesive MCF10A cells formed a core surrounded by low cohesive MDA-MB-231 cells on the periphery, consistent with the differential adhesion hypothesis (DAH). Interestingly, this aggregate morphology was completely inverted when the cells were free to grow. At an initial seeding ratio of 1 : 1 (MDA-MB-231 : MCF10A), the fast growing MCF10A cells segregated in the periphery while the slow growing MDA-MB-231 cells stayed in the core. Another morphology developed at an inequal seeding ratio (4 : 1), that is, the cell mixtures developed a side-by-side aggregate morphology. We conclude that the cell self-organization depends not only on the cell cohesive properties but also on the cell seeding ratio and proliferation. Furthermore, by taking advantage of the cell self-organization, we purified human embryonic stem cells-derived pancreatic progenitors (hESCs-PPs) from co-cultured feeder cells without using any additional tools or labels. PMID- 27275625 TI - The prevalence of hepatitis C virus infection in Egypt 2015: implications for future policy on prevention and treatment. AB - BACKGROUND & AIMS: In 2015, a national Egyptian health issue survey was conducted to describe the prevalence of hepatitis C virus (HCV) infection. In this paper, we describe the HCV burden in 2015, compare the results with the national survey conducted in 2008, and discuss the implications of the new findings on prevention of HCV in Egypt. METHODS: A multistage probability sampling approach was used, similar to the national demographic survey conducted in 2008. More than 90% of sampled individuals complied with the interview and provided blood samples. RESULTS: In the 15-59-year age groups, the prevalence of HCV antibody was found to be 10.0% (95% CI 9.5-10.5) and that of HCV RNA to be 7.0% (95% CI 6.6-7.4). In children, 1-14 years old, the prevalence of HCV antibody and HCV RNA were 0.4% (95% CI 0.3-0.5) and 0.2% (95% CI 0.1-0.3) respectively. Approximately, 3.7 million persons have chronic HCV infection in the age group 15-59 in 2015. An estimated 29% reduction in HCV RNA prevalence has been seen since 2008, which is largely attributable to the ageing of the group infected 40-50 years ago during the mass schistosomiasis treatment campaigns. Prevention efforts may have also contributed to this decline, with an estimated 75% (95% CI 6-45) decrease in HCV incidence in the 0-19 year age groups over the past 20 years. CONCLUSIONS: These findings can be used to shape future HCV prevention policies in Egypt. PMID- 27275626 TI - Living with Chronic Spontaneous Urticaria in Italy: A Narrative Medicine Project to Improve the Pathway of Patient Care. AB - Chronic spontaneous urticaria (CSU) is perceived as a difficult to manage disease with negative impact on quality of life. The aim of this study was to highlight how to improve the care of people with CSU, using the methodology of narrative medicine. From June 2014 to March 2015, CSU-diagnosed patients and their physicians were asked to record their experiences of the condition in writing. Fourteen healthcare teams participated: 41% considered CSU as a challenge to overcome, while 22% experienced CSU as a big commitment. The number of professional involved was evaluated as insufficient in 11 hospitals. Seventy-five percent of the 190 Italian patients had visited 3 or more physicians before receiving a final diagnosis, with a perceived waste of time and resources. The therapeutic pathways were described as unsatisfactory in 83% of cases. As a result, anger and frustration were life-dominant emotions in 92% of patients. The critical points of the care pathway are related to organizational issues and lack of awareness. PMID- 27275627 TI - Targeted Cancer Therapy: Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity (Adv. Healthcare Mater. 11/2016). AB - On page 1310 J. S. Merzaban, A. E. Porter, and co-workers present fluorescently labeled RGD-targeted ZnO nanoparticles (NPs; green) for the targeted delivery of cytotoxic ZnO to integrin alphavbeta3 receptors expressed on triple negative breast cancer cells. Correlative light-electron microscopy shows that NPs dissolve into ionic Zn(2+) (blue) upon uptake and cause apoptosis (red) with intra-tumor heterogeneity, thereby providing a possible strategy for targeted breast cancer therapy. Cover design by Ivan Gromicho. PMID- 27275629 TI - Microfluidics-Based Biosensors: A Microfluidic Paper-Based Origami Nanobiosensor for Label-Free, Ultrasensitive Immunoassays (Adv. Healthcare Mater. 11/2016). AB - The first microfluidic paper-based origami nano-biosensor featuring zinc oxide nanowires and an electrochemical impedance spectroscopy biosensing mechanism, for label-free, ultrasensitive immunoassays is reported by X. Li and X. Liu on page 1326. The sensor consists of cellulose paper, a carbon ink electrode, and zinc oxide nanowires directly grown on the top. Possible parallelization of assays and high storage stability render the sensor promising for clinical diagnostics applications. PMID- 27275631 TI - Constructing Hierarchically Hollow Core-Shell MnO2 /C Hybrid Spheres for High Performance Lithium Storage. AB - Hierarchical MnO2 /C hybrid spheres (MCS@MnO2 ), consisting of numerous hollow core-shell MnO2 @C nanospheres, are developed via a facile deposition process. The well-defined inner voids and robust carbon framework endow MCS@MnO2 with excellent mechanical stability, efficient utilization of MnO2 , and enhanced reaction kinetics for Li-ion batteries, therefore leading to large specific capacities, superior rate capability, and long-term cycling stability. PMID- 27275633 TI - Oxygen Atom Exchange between H2O and Non-Heme Oxoiron(IV) Complexes: Ligand Dependence and Mechanism. AB - Detailed studies of oxygen atom exchange (OAE) between H2(18)O and synthetic non heme oxoiron(IV) complexes supported by tetradentate and pentadentate ligands provide evidence that they proceed by a common mechanism but within two different kinetic regimes, with OAE rates that span 2 orders of magnitude. The first kinetic regime involves initial reversible water association to the Fe(IV) complex, which is evidenced by OAE rates that are linearly dependent on [H2(18)O] and H2O/D2O KIEs of 1.6, while the second kinetic regime involves a subsequent rate determining proton-transfer step between the bound aqua and oxo ligands that is associated with saturation behavior with [H2(18)O] and much larger H2O/D2O KIEs of 5-6. [Fe(IV)(O)(TMC)(MeCN)](2+) (1) and [Fe(IV)(O)(MePy2TACN)](2+) (9) are examples of complexes that exhibit kinetic behavior in the first regime, while [Fe(IV)(O)(N4Py)](2+) (3), [Fe(IV)(O)(BnTPEN)](2+) (4), [Fe(IV)(O)(1Py BnTPEN)](2+) (5), [Fe(IV)(O)(3Py-BnTPEN)](2+) (6), and [Fe(IV)(O)(Me2Py2TACN)](2+) (8) represent complexes that fall in the second kinetic regime. Interestingly, [Fe(IV)(O)(PyTACN)(MeCN)](2+) (7) exhibits a linear [H2(18)O] dependence below 0.6 M and saturation above 0.6 M. Analysis of the temperature dependence of the OAE rates shows that most of these complexes exhibit large and negative activation entropies, consistent with the proposed mechanism. One exception is complex 9, which has a near-zero activation entropy and is proposed to undergo ligand-arm dissociation during the RDS to accommodate H2(18)O binding. These results show that the observed OAE kinetic behavior is highly dependent on the nature of the supporting ligand and are of relevance to studies of non-heme oxoiron(IV) complexes in water or acetonitrile/water mixtures for applications in photocatalysis and water oxidation chemistry. PMID- 27275634 TI - Delivery room hospice. AB - : Advances in perinatal science over the past five decades have reduced the practical 'threshold of viability' by approximately one week every 10 years such that survivors are expected as early as 22 weeks. Ethical standards regarding treatment of this periviable patient population remain enigmatic. CONCLUSION: We review limitations in the current ethical rationale for caring for these infants in the delivery room and introduce an alternative utilising a delivery room hospice care approach involving the administration of opioids. PMID- 27275635 TI - [Introduction to the molecular diagnostic methods of oncohematology]. AB - Owing to our rapidly expanding knowledge on the genetic background of various oncohematologic diseases and the introduction of novel targeted therapies, molecular genetic techniques have been playing an increasingly important role in the diagnostics and follow-up of hematological malignancies. The various DNA- and RNA-based in situ hybridization, polymerase chain reaction and sequencing technologies are of key significance in diagnostics, classification and prognostic assessment of these diseases, as well as in the monitoring of minimal residual disease and selection of the most appropriate targeted therapy. This review provides an overview on the background and applications of the molecular methods most commonly used in oncohematological diagnostics. PMID- 27275632 TI - Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. AB - IMPORTANCE: Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE: To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50-76 years]; 55% female). Patients registered between May 29, 2013, and February 7, 2014. INTERVENTIONS: Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5 fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES: Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS: The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%-83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%-88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. CONCLUSIONS AND RELEVANCE: The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial's completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01821612. PMID- 27275636 TI - [Molecular and histological features of diffuse large B-cell lymphoma]. AB - Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoproliferative disease of mature B cells, representing the most common lymphoid malignancy of adulthood. There are multiple distinct subgroups of DLBCL in the 2008 WHO classification, organ specific forms, DLBCL associated with immunodeficiency and viral infections and rare CD20 negative and intermediate forms. However, most of the cases are still classified under the DLBCL not otherwise specified (NOS) category. This group of disease shows remarkable heterogeneity with respect to clinical presentation, biology and response to treatment, reflecting several molecular subgroups: the origin of B cells at various developmental stages, the oncogenic pathways that drive tumor development and also epigenetic changes and mutations involving the escape of immune surveillance. Contemporary chemo-immunotherapy does not result in durable remissions in as many as 30% of the cases. To achieve longer survival, the definition of new biomarkers are needed for targeted therapy based on better subgrouping of tumors according to the molecular pathways involved in lymphomagenesis. This paper summarizes the most important features influencing the outcome of this broad disease at the level of morphology, phenotype and genotype and gives a guideline for the routine pathological practice at present for the diagnostics of DLBCL treated by chemo-immunotherapy. PMID- 27275637 TI - [The role of PET/CT investigation in the management of patients with diffuse large B-cell lymphoma]. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma (NHL). Although this lymphoma is curable, 40% of patients with DLBCL will die of relapsed or refractory disease. 18F-Fluoro-deoxyglucose positron emission tomography (FDG-PET) is a noninvasive, 3-dimensional, functional imaging modality. When combined with the anatomical imaging tool computed tomography (CT), PET/CT can differentiate among others necrotic masses and viable tumors. PET scan has become a basic clinical tool for staging and response assessment in aggressive lymphomas, such as DLBCL. It has been evaluated in pretreatment staging, restaging, monitoring during therapy, post-therapy surveillance and assessment of transformation. Based on the preliminary results of several studies FDG-PET scans play an important role in the early assessment of treatment response, in planning of the treatment including radiation therapy and in the estimation of prognosis. PMID- 27275638 TI - [The genetic landscape of chronic lymphocytic leukemia]. AB - Chronic lymphocytic leukemia (CLL) is the most frequent mature B-cell non Hodgkin's lymphoma in the Western countries. The recent next-generation sequencing (NGS) studies lead to an exponential increase in our knowledge of the pathogenesis and progression of CLL. Whole genome and exome sequencing studies revealed a remarkable inter- and intra-patient genetic heterogeneity with a significant therapy-induced clonal evolution in the majority of the patients. Driver mutations were identified in components of various signalling pathways and cellular processes with notable prognostic and therapeutic relevance. Interestingly, these studies revealed only a few genes mutated in at least 15-20% of the patients with a larger number of genes mutated in a smaller proportion of patients. This improved understanding of the genomic landscape of CLL has opened new avenues for a more precise patient stratification and rational application of novel, more effective targeted therapies. PMID- 27275639 TI - [Treatment of patients with chronic lymphocytic leukemia]. AB - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western countries. The abnormal B lymphocytes progress into the blood and infiltrate the bone marrow, liver, spleen and lymph nodes. CLL is a disease of the adults and older individuals who often have coexisting conditions. It usually progresses slowly, but in patients who need treatment, CLL eventually returns. For relapsed, refractory patients treatment options are limited. The only curative treatment is bone marrow transplantation. However, the new, alternative therapeutics show superior efficacy in CLL than standard regimens. The aim of this review is to summarize the most important therapeutic aspects of CLL and to give an insight into the novel treatment options. PMID- 27275641 TI - [The pathology and genetic background of myeloma]. AB - Plasma cell myeloma is a heterogeneous hematologic malignancy of plasma cells, occurring dominantly in the elderly population. It is now accepted that all myeloma cases are preceded by a clinically silent expansion of clonal plasma cells, known as monoclonal gammopathy of undetermined significance. Our knowledge on the genetics of myeloma is still limited and lags behind other well characterized hematological malignancies. One of the reasons of this fact is the difficulty to induce metaphases within the malignant plasma cell population. With the development of new molecular techniques (microarrays and next generation sequencing), our understanding of the pathogenesis and progression of myeloma has been highly improved in the past years. This review offers an insight into this newly gained knowledge. PMID- 27275640 TI - [Novelties in the diagnostics and therapy of hairy cell leukemia]. AB - Differential diagnosis of hairy cell leukemia (HCL) and related disorders (hairy cell leukemia variant and splenic marginal zone lymphoma) is of utmost importance since the treatment and prognosis of these lymphomas differ. Since 2011 diagnosis of hairy cell leukemia has been easier because of discovery of the disease defining somatic mutation BRAF V600E mutation, which has been also known as driver mutation in malignant melanoma. The presence of this mutation enabled targeted molecular therapy in HCL as well. As first line therapy purine nucleoside analogues are the gold standard, but refractory/relapsed patient are candidates for targeted BRAF-inhibitor therapy. This manuscript serves as guidance in making diagnosis and standard treatment of HCL, and summarizes newest data about molecular therapy, including our single center experience collected from 75 patients. PMID- 27275642 TI - [Multiple myeloma and other plasma cell dyscrasias]. AB - Multiple myeloma is the most common primary malignant disease of bone marrow. It mainly occurs among elderly people and, according to international databases, it is twice as frequent in men, however in our country this fact cannot be observed because of the high male mortality rate. The presence of this disease increased by more than one and the half times during the last 60 years. The five year survival for multiple myeloma has increased from 25% to 40% since the seventies due to high-dose chemotherapy followed by autologous stem cell transplantation and the new anti-myeloma drugs which were introduced in the last decade, such as immunomodulators (IMiD) like thalidomide, lenalidomide, pomalidomide and proteasome inhibitors (PI) like bortezomib, carfilzomib, ixazomib. The number of treatment options are growing fast, and not only because of using new combinations of medications, but also due to the development of investigational products which are available for the patients by participating in a clinical trial. PMID- 27275643 TI - [Chemotherapy-induced peripheral neuropathy: characteristics, diagnosis and treatment]. AB - Longer remissions and better overall survival rates can be achieved with the introduction of new, effective treatments and targeted therapies in the past 1-2 decades, however, the incidence of side effects is also increasing parallelly. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially debilitating side effect due to peripheral somatic or autonomic nerve dysfunction. CIPN becomes increasingly important, as it affects patients' quality of life, and it is very often a dose limiting factor with the potential for reduced treatment efficacy. The pathomechanism, diagnosis, prevention and treatment possibilities are described in this review with special attention to the different groups of drugs. PMID- 27275644 TI - Gas phase basicities of polyfunctional molecules. Part 5: Non-aromatic sp2 nitrogen containing compounds. AB - This paper constitutes the fifth part of a general review of the gas-phase protonation thermochemistry of polyfunctional molecules (Part 1: Theory and methods, Mass Spectrom Rev 2007, 26:775-835, Part 2: Saturated basic sites, Mass Spectrom Rev 2012, 31:353-390, Part 3: Amino acids, Mass Spectrom Rev 2012, 31:391-435, Part 4: Carbonyl as basic site, Mass Spectrom Rev 2015, 34:493-534). This part is devoted to non-aromatic molecules characterized by a lone pair located on a sp2 nitrogen atom, it embraces functional groups such as imines, amidines, guanidines, diazenes, hydrazines, oximes, and phosphazenes. Specific examples are examined under five major chapters. In the first one, aliphatic and unsaturated (conjugated and cyclic) imines, hydrazones, and oximes are considered. A second chapter describes the protonation energetic of aliphatic, conjugated, or cyclic amidines. Guanidines, polyguanides, and biomolecules containing guanidine were examined in the third chapter. A fourth chapter describes the particular case of the phosphazene molecules. Finally, diazenes and azides were considered in the last chapter. Experimental data were re-evaluated according to the presently adopted basicity scale, i.e., PA(NH3 ) = 853.6 kJ/mol, GB (NH3 ) = 819 kJ/mol. Structural and energetic information given by G4MP2 quantum chemistry computations on typical systems are presented. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:139-170, 2018. PMID- 27275645 TI - Niche overlap analysis of a lizard assemblage from the Atlantic Rainforest, evaluation of arsenic toxicity in cladocerans, and molecular biology of mycoplasmas. PMID- 27275646 TI - Pertuzumab and trastuzumab: the rationale way to synergy. AB - It has now been 15 years since the HER2-targeted monoclonal antibody trastuzumab was introduced in clinical and revolutionized the treatment of HER2-positive breast cancer patients. Despite this achievement, most patients with HER2 positive metastatic breast cancer still show progression of their disease, highlighting the need for new therapies. The continuous interest in novel targeted agents led to the development of pertuzumab, the first in a new class of agents, the HER dimerization inhibitors. Pertuzumab is a novel recombinant humanized antibody directed against extracellular domain II of HER2 protein that is required for the heterodimerization of HER2 with other HER receptors, leading to the activation of downstream signalling pathways. Pertuzumab combined with trastuzumab plus docetaxel was approved for the first-line treatment of patients with HER2-positive metastatic breast cancer and is currently used as a standard of care in this indication. In the neoadjuvant setting, the drug was granted FDA accelerated approval in 2013. Pertuzumab is also being evaluated in the adjuvant setting. The potential of pertuzumab relies in the dual complete blockade of the HER2/3 axis when administered with trastuzumab. This paper synthetises preclinical and clinical data on pertuzumab and highlights the mechanisms underlying the synergistic activity of the combination pertuzumab-trastuzumab which are essentially due to their complementary mode of action. PMID- 27275647 TI - Thermal boundary conductance enhancement using experimentally achievable nanostructured interfaces - analytical study combined with molecular dynamics simulation. AB - Interfacial thermal resistance presents great challenges to the thermal management of modern electronics. In this work, we perform an analytical study to enhance the thermal boundary conductance (TBC) of nanostructured interfaces with square-shape pillar arrays, extendable to the characteristic lengths that can be fabricated in practice. As a representative system, we investigate a SiC substrate with the square-shape pillar array combined with epitaxial GaN as the nanostructured interface. By applying a first-order ray tracing method and molecular dynamics simulations to analyze phonon incidence and transmission at the nanostructured interface, we systematically study the impact of the characteristic dimensions of the pillar array on the TBC. Based on the multi scale analysis we provide a general guideline to optimize the nanostructured interfaces to achieve higher TBC, demonstrating that the optimized TBC value of the nanostructured SiC/GaN interfaces can be 42% higher than that of the planar SiC/GaN interfaces without nanostructures. The model used and results obtained in this study will guide the further experimental realization of nanostructured interfaces for better thermal management in microelectronics. PMID- 27275648 TI - Photoinduced Electron and Energy Transfer in a Molecular Triad Featuring a Fullerene Redox Mediator. AB - In order to investigate the possibility of a fullerene acting as an electron and/or singlet energy relay between a donor chromophore and an acceptor, a triad consisting of a fullerene (C60) covalently linked to both a porphyrin energy and electron donor (P) and a beta-tetracyanoporphyrin energy and electron acceptor (CyP) was synthesized. Steady state and time-resolved spectroscopic investigations show that the porphyrin first excited singlet state donates singlet excitation and an electron to the fullerene and also donates singlet excitation to the CyP. All three processes differ in rate constant by factors of <=1.3, and all are much faster than the decay of (1)P-C60-CyP by unichromophoric processes. The fullerene excited state accepts an electron from P and donates singlet excitation energy to CyP. The P(*+)-C60(*-)-CyP charge-separated state transfers an electron to CyP to produce a final P(*+)-C60-CyP(*-) state. The same state is formed from P-C60-(1)CyP. Overall, the final charge-separated state is formed with a quantum yield of 85% in benzonitrile, and has a lifetime of 350 ps. Rate constants for formation and quantum yields of all intermediate states were estimated from results for the triad and several model compounds. Interestingly, the intermediate P(*+)-C60(*-)-CyP charge-separated state has a lifetime of 660 ps. It is longer lived than the final state in spite of stronger coupling of the radical ions. This is ascribed to the fact that recombination lies far into the inverted region of the Marcus rate constant vs thermodynamic driving force relationship. PMID- 27275649 TI - Combining Bulk/Surface Engineering of Hematite To Synergistically Improve Its Photoelectrochemical Water Splitting Performance. AB - One of the most promising candidates for photoelectrochemical (PEC) water splitting photoanode is hematite (alpha-Fe2O3) due to its narrow bandgap and chemical stability. However, the poor bulk/surface kinetics of hematite limits its PEC performance. Herein, a facile two-step approach is reported to synergistically improve the PEC performance of Fe2O3. First, through bulk engineering of Ti doping, the photocurrent density of Ti-Fe2O3 photoanode (1.68 mA cm(-2) at 1.23 VRHE) shows a 3-fold increase compared with that of pure Fe2O3 photoanode (0.50 mA cm(-2) at 1.23 VRHE). Second, the photocurrent density of Ti Fe2O3 photoanode could be further enhanced to 2.31 mA cm(-2) by surface engineering of FeOOH. The enhanced PEC water splitting performance is proposed to be the synergistic effect of bulk and surface engineering, which can be mainly attributed to the great increase of charge separation efficiency and surface transfer efficiency. PMID- 27275650 TI - Commentary on "Phimosis with Preputial Fissures as a Predictor of Undiagnosed Type 2 Diabetes in Adults". PMID- 27275651 TI - Ticagrelor versus prasugrel in patients with high on-clopidogrel treatment platelet reactivity after PCI: The ISAR-ADAPT-PF study. AB - Patients with high on-treatment platelet reactivity (HTPR) on clopidogrel are at high risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). The aim of the ISAR-ADAPT-PF study was to assess the antiplatelet efficacy of ticagrelor versus prasugrel in patients with HTPR on clopidogrel. In a prospective and randomized clinical study, 70 patients with HTPR on clopidogrel loading dose (LD) within 24 h post PCI were assigned to receive either ticagrelor [180 mg LD followed by 90 mg maintenance dose (MD) twice daily] or prasugrel (60 mg LD followed by 10 mg MD once daily). The adenosine diphosphate-induced platelet aggregation assessed on the Multiplate analyzer on day 2 after randomization (primary end point) was as follows: the mean difference between the two treatment groups was 6 aggregation units (AU) * min with an upper 95% confidence interval (CI) of 41 AU * min, which was greater than the predefined noninferiority margin of 18 AU * min (P for noninferiority = 0.29). However, no significant differences in absolute platelet reactivity levels between ticagrelor- versus prasugrel-treated patients at that time point were observed (138 +/- 100 AU * min vs. 132 +/- 64 AU * min, P for superiority = 0.77). In conclusion, neither drug was statistically more effective for inhibition of platelet aggregation in patients with HTPR on clopidogrel post PCI, although the study could not formally demonstrate the assumed noninferiority of ticagrelor versus prasugrel. PMID- 27275653 TI - Comparing Gonioscopy With Visante and Cirrus Optical Coherence Tomography for Anterior Chamber Angle Assessment in Glaucoma Patients. PMID- 27275652 TI - Outcomes of Preoperative MRI-Guided Needle Localization of Nonpalpable Mammographically Occult Breast Lesions. AB - OBJECTIVE: MRI-guided needle localization allows access to MRI-detected mammographically occult breast lesions that are not amenable to MRI-guided biopsy. The purpose of this study was to examine the safety and outcomes of MRI guided needle localization. MATERIALS AND METHODS: Ninety-nine consecutive breast lesions that underwent preoperative MRI-guided needle localization were identified. Clinical indications for breast MRI, reasons for performing MRI guided needle localization, and surgical pathology results were recorded. Lesion characteristics, procedure time, and complications were assessed. RESULTS: Of 99 lesions, 60 (60.6%) were in a location inaccessible for MRI biopsy, necessitating MRI-guided needle localization. Histologic evaluation revealed 38 (38.4%) carcinomas, 31 (31.3%) high-risk lesions, and 30 (30.3%) benign lesions. Carcinoma was more likely to be found in women with known cancer (31/61 [50.8%]; p = 0.003) than in women undergoing imaging for high-risk screening (2/18 [11.1%]) or problem solving (6/20 [30%]). Masses (p = 0.013) and foci (p < 0.001) were more likely to be malignant than were lesions with nonmass enhancement. Foci were significantly more often malignant compared with all other lesion types (9/10 [90%]; p < 0.001). The mean (+/- SD) procedure time was 32.9 +/- 9.39 minutes. All lesions were occult on specimen radiographs. There were no procedure related complications. CONCLUSION: The positive predictive value of MRI-guided needle localization (38.4%) is comparable to that of mammography- and tomosynthesis-guided localizations and is highest in women with a known diagnosis of cancer. It is highly accurate in targeting small enhancing lesions, thereby improving surgical management. MRI-guided needle localization is a safe, accurate, and time-efficient procedure. PMID- 27275654 TI - A Pilot Evaluation Assessing the Ease of Use and Accuracy of the New Self/Home Tonometer IcareHOME in Healthy Young Subjects. AB - PURPOSE: We investigated the ease of use and accuracy of a new self/home tonometer (IcareHOME) versus Goldmann applanation tonometry (GAT) and the Icare tonometer (Icare) by measuring the diurnal intraocular pressure (IOP). PATIENTS AND METHODS: The right eyes of 43 healthy young subjects were studied. The IOP was measured using the IcareHOME, GAT, and Icare 6 times a day, every 2 hours, from 8:00 to 18:00. The coincidence of the diurnal curves among all tonometers was analyzed using a linear mixed model. The intradevice and interdevice agreement was evaluated using the intraclass correlation coefficients (ICC) and Bland-Altman method. The subjects' perception of the IcareHOME was evaluated using a questionnaire. RESULTS: The liner mixed model showed similar diurnal IOP curves for all tonometers (P=0.543); however, significant differences were observed between the tonometers over time (P<0.001). The intradevice repeatability was ICC>0.8 among all tonometers, although the interdevice agreement was lowest between the IcareHOME and GAT (ICC=0.641). The IOP values were significantly lower for the IcareHOME than for the GAT at 12:00, 16:00, and 18:00 (P<0.05, Tukey-Kramer test). The mean differences between the Icare and IcareHOME and GAT and IcareHOME were 0.83 and 1.03 mm Hg, respectively (95% limit of agreement: -4.17 to 5.84 mm Hg and -3.91 to 5.98 mm Hg, respectively). Regarding the subjects' perception of handling the IcareHOME, 17 (39.5%) subjects answered "easy to use," 20 (46.5%) answered "normal," and six (13.9%) answered "difficult to use." CONCLUSIONS: The IcareHOME can be used as a self/home tonometer; however, it may result in lower IOP values. PMID- 27275655 TI - The Effects of Physical Exercises on Ocular Physiology: A Review. AB - Sport has been known to be one of the most important factors in preventing cardiovascular disorders; some studies suggest its role in preventing neurodegenerative diseases. This review discusses the results of various studies regarding the effects of physical exercises on intraocular pressure (IOP), myopia, certain physical parameters of the eye, ocular blood flow, and retinal electrical function. Although dynamic exercises are known to reduce IOP from 1.2 to 5.9 mm Hg only for a short period of time, uncertainty persists about whether isometric exercises or activities such as yoga can increase IOP up to 16.7 mm Hg. There has been an established connection between the time being spent outdoor and reduction in the odds of myopia-2% less odds for every hour spent outdoor. Physical activity and the level of physical fitness have an impact on the changes of b-wave electroretinogram and P100. Physical exercises increase perfusion pressure up to 190% baseline and also increase choroidal blood flow up to 140%, thus providing more blood to retina. Sport-induced change on visual field is a subject of controversy. Majority of patients show a better ocular physiological function due to sports and sports are thus considered essential for preventing common ocular diseases. Further research should focus more on long-term effects of sport-induced changes in ocular physiology and newly discovered techniques may be utilized for such purposes. PMID- 27275656 TI - Juvenile-onset Normal Tension Glaucoma From Chronic, Recurrent Low Cerebrospinal Fluid Pressure. AB - INTRODUCTION: The evidence for low cerebrospinal fluid pressure (CSFP) as a key parameter in the pathogenesis of glaucoma is increasing. Primate models have demonstrated the onset normal tension glaucoma (NTG) from experimentally induced chronic intrathecal hypotension; an approach not possible in human subjects. CASE PRESENTATION: A 27-year-old man presented with a central scotoma in his left eye. He had undergone 8 CSF shunt revision procedures over a 25-year period secondary to recurrent low CSFP following surgical excision of a pinealoblastoma, aged 2. A focal nerve fiber layer defect was detected in the left eye associated with reduced retinal sensitivity on microperimetry. Three adjacent optic disc hemorrhages had been documented in the same position over an 18-month period. A diagnosis of left-sided NTG was made; the patient was started on Latanoprost 0.005%. A new generation CSF shunting device (ProGAV)-which neutralizes CSFP fluctuations analogously to trabeculectomy surgery for intraocular pressure-was considered necessary in this patient to alleviate persistent headaches and reduce the risk of progressive glaucomatous visual loss. CONCLUSIONS: This exceptional case illustrates how premature onset NTG may occur as a result of chronic, recurrent intrathecal hypotension-a "pure" human model. We describe an original management approach of implanting an adjustable, programmable CSF shunt valve (ProGAV) to reduce fluctuations in the translaminar cribrosa pressure difference, and reduce the risk of glaucomatous visual loss. PMID- 27275657 TI - Comparison of Rotational Thromboelastography Findings in Pseudoexfoliation Syndrome Patients and Healthy Controls. AB - PURPOSE: Rotational thromboelastography (ROTEM) is a useful test for studying the characteristics of fibrin clot formation. As patients with pseudoexfoliation (PEX) have an increased risk for thrombotic events, clot-forming dysfunction may play a role. The aim of this study is to compare ROTEM findings in PEX syndrome patients with age-matched and sex-matched healthy controls. PATIENTS AND METHODS: A total of 21 patients with PEX syndrome and 22 age-matched and sex-matched healthy controls were included. All study participants underwent detailed ophthalmologic and systemic medical examination, including blood pressure measurement, hemoglobin-hematocrit levels, platelet count, coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels. Peripheral blood samples were collected and analyzed with ROTEM Coagulation Analyzer. RESULTS: The mean age of patients with PEX and controls was 66.5+/-8.3 and 65.9+/-9.5 years, respectively (P=0.7). The 2 groups did not differ with respect to age, sex, hemoglobin, hematocrit, platelet numbers, prothrombin time, activated partial thromboplastin time, fibrinogen levels, D-dimer levels, and glucose levels. When extrinsic thromboelastometry results were analyzed, PEX patients showed a significantly decreased clotting time when compared with healthy controls (79.8 vs. 98.0 s; P=0.01), indicating faster clot formation. Other ROTEM parameters did now show any difference between the 2 groups. CONCLUSIONS: PEX patients showed faster clotting time when compared with healthy controls. This fibrin clot formation dysfunction may lead to vascular thrombotic events in these patients. Further studies are needed to elucidate the exact underlying mechanism of thrombosis seen in PEX patients. PMID- 27275658 TI - [Health care plan: a treatment as a piece of a puzzle. Considerations with respect to judgement of the Central Disciplinary Board for Health Care]. AB - When faced with the question whether a particular treatment is indicated, dentists have to ask themselves to what extent it fits within a health care goal. If it does not, then the indication is usually rejected because it is in conflict with professional standards. Dentists who nevertheless consider such an indication have to bear the responsibility to make clear to the patient not only the general risks of a certain treatment but also the additional risks associated with the hazardous indication. PMID- 27275659 TI - [Gout in the temporomandibular joint]. AB - A 76-year-old woman, with a medical history of diabetes mellitus and hypertension, presented herself to an oral and maxillofacial surgeon with a sudden pre-auricular swelling of the right temporomandibular joint. As a result of the atypical clinical appearance and signs of local destruction in the initial panoramic x-ray, a malign process was first eliminated from consideration. With the aid of extensive diagnostics and an open biopsy, the diagnosis of gout was established. PMID- 27275660 TI - [Oral hygiene behaviour of a group of healthy students]. AB - The aim of this cross-sectional study was to get a picture of the daily oral hygiene behaviour of a group of healthy Dutch students in the age range of 18 to 30 years and its relation to oral health. On the basis of a questionnaire, the students were interviewed concerning their oral hygiene behaviour. The level of gingivitis and the level of tongue coating were analysed in relation to the results of the questionnaire. The study revealed that the majority brushed their teeth twice a day. The different methods of tooth brushing and the use of a manual or electric toothbrush had no significant effect on the clinical parameters in this study population. A small group used an interdental cleaning method daily. The toothpick was the aid most often used and its use resulted in a significant reduction of the tendency to interdental bleeding. The use of a tongue cleaner had no statistically significant effect on the level of tongue coating. PMID- 27275661 TI - [Dissertations 25 years after date 46. Treatment of mandibular fractures]. AB - In the 1980s, professionals wanted to determine what the best method was for treating fractures of the mandibula. The emergence of osteosynthesis plates in the late 1960s, bringing with them the possibility of immediate functional restoration, had had a dramatic effect. This type of plate was most often placed by means of an extra-oral incision. A decade later, a system of smaller plates was introduced, which were placed intra-orally. A doctoral research project from 1991 investigated the advantages and disadvantages of the various methods of treating a mandibular fracture in order to determine which was most applicable. The importance of careful assessment on the basis of the type of fracture and the desired firmness of the osteosynthesis, described in the dissertation, is still decisive in conclusions concerning surgical treatment method and choice of material. PMID- 27275662 TI - [Is amalgam stained dentin a proper substrate for bonding resin composite?]. AB - After the removal of amalgam restorations, black staining of dentin is often observed, which is attributed to the penetration of corrosion products from amalgam. A study was carried out to determine whether this amalgam stained dentin is a proper substrate for bonding resin composites. A literature study and an in vitro study showed that Sn and Zn in particular are found in amalgam stained dentin, and this was the case only in demineralised dentin. In vitro, demineralised dentin acted as porte d'entrEe for amalgam corrosion products. Bond strength tests with 5 adhesive strategies showed no differences between bond strengths to amalgam stained and to sound dentin, but did show different failure types. A clinical study showed good survival of extensive cusp replacing resin composite restorations. No failures were attributed to inadequate adhesion. It is concluded that staining of dentin by amalgam corrosion products has no negative effect upon bond strength of resin composite. It is suggested that Sn and Zn may have a beneficial effect upon dentin, thus compensating the effects of previous carious attacks, preparation trauma and physico-chemical challenges during clinical lifetime. PMID- 27275663 TI - Electrochemically Induced Nanobubbles between Graphene and Mica. AB - We present a new method to create dynamic nanobubbles. The nanobubbles are created between graphene and mica by reducing intercalated water to hydrogen. The nanobubbles have a typical radius of several hundred nanometers, a height of a few tens of nanometers and an internal pressure in the range of 0.5-8 MPa. Our approach paves the way to the realization of nanobubbles of which both size and internal pressure are tunable. PMID- 27275664 TI - Comparison of multiple genotyping methods for the identification of the cancer predisposing founder mutation p.R337H in TP53. AB - Germline mutations in the TP53 gene are associated with Li-Fraumeni and Li Fraumeni-Like Syndromes, characterized by increased predisposition to early-onset cancers. In Brazil, the prevalence of the TP53-p.R337H germline mutation is exceedingly high in the general population and in cancer-affected patients, probably as result of a founder effect. Several genotyping methods are used for the molecular diagnosis of LFS/LFL, however Sanger sequencing is still considered the gold standard. We compared performance, cost and turnaround time of Sanger sequencing, PCR-RFLP, TaqMan-PCR and HRM in the p.R337H genotyping. The performance was determined by analysis of 95 genomic DNA samples and results were 100% concordant for all methods. Sequencing was the most expensive method followed by TaqMan-PCR, PCR-RFLP and HRM. The overall cost of HRM increased with the prevalence of positive samples, since confirmatory sequencing must be performed when a sample shows an abnormal melting profile, but remained lower than all other methods when the mutation prevalence was less than 2.5%. Sequencing had the highest throughput and the longest turnaround time, while TaqMan-PCR showed the lowest turnaround and hands-on times. All methodologies studied are suitable for the detection of p.R337H and the choice will depend on the application and clinical scenario. PMID- 27275665 TI - The Brazilian Hereditary Cancer Network: historical aspects and challenges for clinical cancer genetics in the public health care system in Brazil. PMID- 27275666 TI - Self-reported cancer family history is a useful tool for identification of individuals at risk of hereditary cancer predisposition syndrome at primary care centers in middle-income settings: a longitudinal study. AB - Analysis of cancer family history (CFH) offers a low-cost genetic tool to identify familial cancer predisposition. In middle-income settings, the scarcity of individual records and database-linked records hinders the assessment of self reported CFH consistency as an indicator of familial cancer predisposition. We used self-reported CFH to identify those families at risk for hereditary cancer syndromes in community-based primary care centers of a low-income Brazilian area. We also evaluated the consistency of the information collected by reassessing CFH five years later. We interviewed 390 families and constructed their pedigrees for genetic cancer risk assessment. We found 125 families affected by cancer, 35.2% with moderate to high risk of familial susceptibility to cancer, a number that represents a relatively high prevalence of potential hereditary cancer syndromes in the overall study sample. Upon reassessment of CFH in 14/20 families that were previously identified as having at least one first-degree and one second-degree relative affected by cancer, and presented moderate to high risk for developing cancer, 90% of initial pedigrees were confirmed. These results demonstrate the reliability of self-reports as a means of early identification of healthy individuals at risk, encouraging the wider use of this method in low- and middle income primary care settings. PMID- 27275667 TI - Mesenchymal stem cell therapy promotes the improvement and recovery of renal function in a preclinical model. AB - Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF. PMID- 27275668 TI - Indole-2-carboxamide-based MmpL3 Inhibitors Show Exceptional Antitubercular Activity in an Animal Model of Tuberculosis Infection. AB - Our team had previously identified certain indolecarboxamides that represented a new chemical scaffold that showed promising anti-TB activity at both an in vitro and in vivo level. Based on mutational analysis using bacteria found resistant to one of these indolecarboxamides, we identified the trehalose monomycolate transporter MmpL3 as the likely target of these compounds. In the present work, we now further elaborate on the SAR of these compounds, which has led in turn to the identification of a new analog, 4,6-difluoro-N-((1R,2R,3R,5S)-2,6,6 trimethylbicyclo[3.1.1]heptan-3-yl)-1H-indole-2-carboxamide (26), that shows excellent activity against drug-sensitive (MIC = 0.012 MUM; SI >= 16000), multidrug-resistant (MDR), and extensively drug-resistant (XDR) Mycobacterium tuberculosis strains, has superior ADMET properties, and shows excellent activity in the TB aerosol lung infection model. Compound 26 is also shown to work in synergy with rifampin. Because of these properties, we believe that indolecarboxamide 26 is a possible candidate for advancement to human clinical trials. PMID- 27275669 TI - Emergency Cricothyrotomy Performed by Surgical Airway-naive Medical Personnel: A Randomized Crossover Study in Cadavers Comparing Three Commonly Used Techniques. AB - BACKGROUND: When conventional approaches to obtain effective ventilation and return of effective spontaneous breathing fail, surgical airway is the last rescue option. Most physicians have a limited lifetime experience with cricothyrotomy, and it is unclear what method should be taught for this lifesaving procedure. The aim of this study is to compare the performance of medical personnel, naive to surgical airway techniques, in establishing an emergency surgical airway in cadavers using three commonly used cricothyrotomy techniques. METHODS: Twenty medical students, without previous knowledge of surgical airway techniques, were randomly selected from their class. After training, they performed cricothyrotomy by three techniques (surgical, Melker, and QuickTrach II) in a random order on 60 cadavers with comparable biometrics. The time to complete the procedure, rate of success, and number of complications were recorded. A success was defined as the correct placement of the cannula within the trachea in 3 min. RESULTS: The success rates were 95, 55, and 50% for surgical cricothyrotomy, QuickTrach, and Melker, respectively (P = 0.025). The majority of failures were due to cannula misplacement (15 of 20). In successful procedures, the mean procedure time was 94 +/- 35 s in the surgical group, 77 +/- 34 in the QuickTrach II group, and 149 +/- 24 in the Melker group (P < 0.001). Few significant complications were found in successful procedures. No cadaver biometric parameters were correlated with success of the procedure. CONCLUSION: Surgical airway-naive medical personnel establish emergency cricothyrotomy more efficiently and safely with the surgical procedure than with the other two commonly used techniques. PMID- 27275670 TI - Surgical Cricothyrotomy, Rather than Percutaneous Cricothyrotomy, in "Cannot Intubate, Cannot Oxygenate" Situation. PMID- 27275734 TI - Iridium-Catalyzed Synthesis of Acylpyridines by [2 + 2 + 2] Cycloaddition of Diynes with Acyl Cyanides. AB - 2-Acylpyridines were prepared by iridium-catalyzed [2 + 2 + 2] cycloaddition of alpha,omega-diynes with acyl cyanides. [Ir(cod)Cl]2/rac-BINAP or F-DPPE is an efficient catalyst for this reaction. The scope and limitations of this reaction have been disclosed. PMID- 27275735 TI - Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China. AB - Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China. PMID- 27275736 TI - Dexamethasone-suppressed Salivary Cortisol and Pain Sensitivity in Female Twins. AB - OBJECTIVES: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with chronic pain. Studying pain sensitivity and the HPA axis could elucidate the role of stress in chronic pain development, which might be influenced by familial factors, including genes. METHODS: Associations between pain sensitivity and salivary cortisol and familial confounding in these associations were examined in 88 female, community-based twin pairs (75% monozygotic, mean age 29 y). Cortisol was assessed after 0.25 mg dexamethasone (DEX), recovery from 0.25 mg DEX, and after 0.5 mg DEX. Cold pressor task (CPT) pain ratings were obtained at threshold and at tolerance. Conditioned pain modulation (CPM) was examined using thermal heat as the testing stimulus and hot water as the conditioning stimulus. Generalized estimating equation models were used and adjusted for baseline pain rating, age, and other relevant covariates. RESULTS: After controlling for baseline cortisol, greater cortisol suppression following DEX administration and lower recovery cortisol levels were associated with higher pain ratings at tolerance during the CPT (Bs=-2.42 to -17.82; Ps=0.031 to<0.001) as well as with reduced CPM (Bs=-0.92 to -1.68; Ps=0.003 to 0.046). Interestingly, familial confounding was evident in the CPT and CPM during recovery from DEX administration, but not immediately following DEX administration. DISCUSSION: These findings contribute to understanding possible mechanisms underlying chronic pain by demonstrating that HPA axis response to negative feedback is related to pain sensitivity. PMID- 27275737 TI - A Conceptual Framework for Understanding the Role of Adverse Childhood Experiences in Pediatric Chronic Pain. AB - OBJECTIVES: This review outlines a conceptual framework adapted from the biopsychosocial model of pain to examine the relationship between adverse childhood experiences (ACEs) and chronic pain in youth to highlight the state of current research and guide future efforts. METHODS: A review of the literature was performed in the areas of ACEs and health outcomes with general adult and pediatric populations in addition to studies within the pain literature. Potential relationships between ACEs, chronic pain, and its impact in youth are outlined and discussed. RESULTS: The literature suggests an association between adverse outcomes of ACEs and chronic pain in children and adolescents although causal links have not been confirmed. However, ACEs are associated with multiple risk factors identified in the biopsychosocial model of pain, and may serve to exacerbate or confer heightened risk for pain and poor outcomes. DISCUSSION: Adverse experiences in childhood may be associated with greater risk for the development/maintenance of chronic pain in youth. More research is needed on ACEs and how they uniquely affect the biopsychosocial mechanisms underlying chronic pain in children throughout the lifespan. PMID- 27275738 TI - Disrupted Bone Metabolism in Long-Term Bedridden Patients. AB - BACKGROUND: Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. METHODS: This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged <30 years at baseline. RESULTS: The bone mineral density was reduced (0.58+/-0.19 g/cm3), and the osteocalcin (13.9+/-12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9+/-134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years. CONCLUSIONS: Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients. PMID- 27275739 TI - Association of IL28B SNPs rs12979860 and rs8099917 on Hepatitis C Virus-RNA Status in Donors/Recipients of Living Donor Liver Transplantation. AB - To investigate the effect of IL28B single nucleotide polymorphisms (SNPs) (rs8099917 and rs12979860) in the donors and recipients on the outcome of Hepatitis C virus-RNA clearance after living donor liver transplantation (LDLT). The rs8099917 and rs12979860 genotypes in 50 donor and recipients pairs were explored on the pre-operative day (POD) and post-operative day 30 (POD30). There was a significant difference in HCV-RNA clearance before (12%, 6/50) and after (48%, 24/50) liver transplantation (P < 0.001). The rs8099917 genotype TT was dominant in both the recipients (82%, 41/50) and donors (86%, 43/50), but had no significant effect on HCV-RNA clearance (87.5%, 21/24) and recurrence (76.9%, 20/26) after LDLT. One recipient was detected with genotype GG on POD, which changed to genotype GT on POD30. Prevalence of rs12979860 genotype CT was 98% (49/50 recipient) and 92% (46/50 donor) and prevalence of genotype CC was 2% (1/50 recipient) and 8% (4/50 donor) on POD and POD30, respectively. Of the 4 recipients with rs12979860 genotype CC on POD30, 3 recipients (12.5%, 3/24) exhibited HCV clearance and 1 experienced recurrence (3.9%, 1/26), however, this was not statistically significant. In conclusion, alterations in IL28B SNP genotype may occur after LDLT, leading to modifications in the host genome or donor proteome by HCV. This predicted mechanism will need to be investigated further. PMID- 27275740 TI - Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils. AB - IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Ralpha and beta) were analyzed using RT/real time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague-Dawley(r) rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Ralpha and IL5Rbeta, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis. PMID- 27275741 TI - SQSTM1 Mutations and Glaucoma. AB - Glaucoma is the most common cause of irreversible blindness worldwide. One subset of glaucoma, normal tension glaucoma (NTG) occurs in the absence of high intraocular pressure. Mutations in two genes, optineurin (OPTN) and TANK binding kinase 1 (TBK1), cause familial NTG and have known roles in the catabolic cellular process autophagy. TKB1 encodes a kinase that phosphorylates OPTN, an autophagy receptor, which ultimately activates autophagy. The sequestosome (SQSTM1) gene also encodes an autophagy receptor and also is a target of TBK1 phosphorylation. Consequently, we hypothesized that mutations in SQSTM1 may also cause NTG. We tested this hypothesis by searching for glaucoma-causing mutations in a cohort of NTG patients (n = 308) and matched controls (n = 157) using Sanger sequencing. An additional 1098 population control samples were also analyzed using whole exome sequencing. A total of 17 non-synonymous mutations were detected which were not significantly skewed between cases and controls when analyzed separately, or as a group (p > 0.05). These data suggest that SQSTM1 mutations are not a common cause of NTG. PMID- 27275742 TI - Wide Variations in Compliance with Tuberculosis Screening Guidelines and Tuberculosis Incidence between Antiretroviral Therapy Facilities - Cote d'Ivoire. AB - BACKGROUND: In Cote d'Ivoire, tuberculosis (TB) is a common cause of death among HIV-infected antiretroviral therapy (ART) enrollees. Ivorian guidelines recommend screening for TB and initiation of TB treatment before ART initiation. Compliance with these guidelines can help reduce TB-related mortality during ART and possibly nosocomial TB transmission. METHODS AND FINDINGS: In a retrospective cohort study among 3,682 randomly selected adults (>=15 years old) starting ART during 2004-2007 at 34 randomly selected facilities, documentation of TB screening completion, prevalence of active TB at ART initiation, and incidence of TB during ART were evaluated. At ART initiation, median age was 36 years, 67% were female, and median CD4 count was 135 cells/MUL. Among all 3,682 enrollees, 73 (2%) were on TB treatment at the time of referral to the ART facility. Among the 3,609 not on TB treatment, 1,263 (36%) were documented to receive some TB screening before ART initiation; 21% were screened for cough, 21% for weight loss, 18% for fever, 18% for TB contacts, and 12% for night sweats. Among the 1,263 screened, 111 (11%) were diagnosed with TB and started TB treatment before ART. No associations between patient characteristics and probability of being screened were noted. However, documentation of TB screening completion before ART varied widely by ART facility from 0-100%. TB incidence during ART was 3.0 per 100 person-years but varied widely by ART facility from 0/100 person-year to 13.1/100 person-years. CONCLUSIONS: Screening for TB before ART initiation was poorly documented. Facility-level variations in TB screening documentation suggest facility-level factors, such as investment in training programs, might determine documentation practices. Targeting under-performing ART facilities with improvement activities is needed. Variations among facilities in TB incidence warrant further research. These incidence variations could reflect differences between facilities in TB screening, diagnostic tests, documentation practices, or TB risk possibly related to infection control practices or local community TB incidence. PMID- 27275743 TI - Matrilineal Behavioral and Physiological Changes following the Death of a Non Alpha Matriarch in Rhesus Macaques (Macaca mulatta). AB - In many species, the loss of alpha matriarchs is associated with a number of negative outcomes such as troop fission, eviction, wounding, and reduced vitality. However, whether the dramatic consequences of their loss are due to their role as an old experienced figure or to their alpha status remains unclear. We tested the hypothesis that in a semi-free ranging colony of rhesus macaques (Macaca mulatta), the death of a non-alpha matriarch, who had a large set of kin, would lead to changes in behavior and physiological stress within her matriline. Following her death, her matriline increased in aggression, vigilance, and social grooming. Additionally, hierarchical stability, measured by levels of rank changes, decreased within her matriline, and levels of intense aggression by high ranking animals were more frequent, as well as matrilineal wounding. Although ordinal rank was positively associated with higher chronic hair cortisol concentrations (HCCs) in the months before the matriarch's death, following her death, only those who experienced large increases in rank within her matriline displayed higher HCCs. Changes in matrilineal stability, aggression, behavior, and HCCs within the other two matrilines in the troop were not evident, although caution is needed due to the small sample sizes. We conclude that the death of the non-alpha matriarch led to matrilineal instability, characterized by higher levels of aggression and subsequent vigilance, rank changes, physiological stress, and grooming. We suggest that non-alpha matriarchs with a large number of kin and social support can be integral to the stability of matrilines. PMID- 27275744 TI - Spatial Configuration of Drought Disturbance and Forest Gap Creation across Environmental Gradients. AB - Climate change is increasing the risk of drought to forested ecosystems. Although drought impacts are often anecdotally noted to occur in discrete patches of high canopy mortality, the landscape effects of drought disturbances have received virtually no study. This study characterized the landscape configuration of drought impact patches and investigated the relationships between patch characteristics, as indicators of drought impact intensity, and environmental gradients related to water availability to determine factors influencing drought vulnerability. Drought impact patches were delineated from aerial surveys following an extreme drought in 2011 in southwestern Australia, which led to patchy canopy dieback of the Northern Jarrah Forest, a Mediterranean forest ecosystem. On average, forest gaps produced by drought-induced dieback were moderate in size (6.6 +/- 9.7 ha, max = 85.7 ha), compact in shape, and relatively isolated from each other at the scale of several kilometers. However, there was considerable spatial variation in the size, shape, and clustering of forest gaps. Drought impact patches were larger and more densely clustered in xeric areas, with significant relationships observed with topographic wetness index, meteorological variables, and stand height. Drought impact patch clustering was more strongly associated with the environmental factors assessed (R2 = 0.32) than was patch size (R2 = 0.21); variation in patch shape remained largely unexplained (R2 = 0.02). There is evidence that the xeric areas with more intense drought impacts are 'chronic disturbance patches' susceptible to recurrent drought disturbance. The spatial configuration of drought disturbances is likely to influence ecological processes including forest recovery and interacting disturbances such as fire. Regime shifts to an alternate, non forested ecosystem may occur preferentially in areas with large or clustered drought impact patches. Improved understanding of drought impacts and their patterning in space and time will expand our knowledge of forest ecosystems and landscape processes, informing management of these dynamic systems in an uncertain future. PMID- 27275746 TI - Correction: Predictive Models of Primary Tropical Forest Structure from Geomorphometric Variables Based on SRTM in the Tapajos Region, Brazilian Amazon. AB - [This corrects the article DOI: 10.1371/journal.pone.0152009.]. PMID- 27275745 TI - Regional Variability of Lifestyle Factors and Hypertension with Prediabetes and Newly Diagnosed Type 2 Diabetes Mellitus: The Population-Based KORA-F4 and SHIP TREND Studies in Germany. AB - OBJECTIVE: Type 2 diabetes mellitus (T2D) shows regional differences in Germany. The purpose of the project was to compare the prevalence of prediabetes and undiagnosed T2D in two regions in Germany, the Northeast and the South, and to evaluate their associations with regional variations in lifestyle factors and hypertension. METHODS: Data from the KORA-F4 study (South Germany, 2006-2008) and the SHIP-TREND study (Northeast Germany, 2008-2012) were used. Participants aged 35-79 years without T2D with an overnight fasting of more than 8 hours and an oral glucose tolerance test were included: KORA-F4: n = 2,616 and SHIP-TREND: n = 1,968. RESULTS: The prevalence of prediabetes/newly diagnosed T2D was especially high in men (about 60%) and women (about 50%) in the Northeast, followed by men (about 50%) and women (about 30%) in the South. Lifestyle factors associated with T2D varied between the regions: more participants in the Northeast were active smokers and the percentages of people with overweight or obesity were greater than in their southern counterparts. However, these differences could not explain the striking disparity in prediabetes/newly diagnosed T2D. The frequency of hypertension was also distinctly higher in the Northeast than in the South and clearly associated with prediabetes/newly diagnosed T2D. Especially in men living in the Northeast, screening individuals with blood pressure >= 140/90mmHg might reveal up to 70% of those with prediabetes/newly diagnosed T2D. CONCLUSIONS: Knowledge about regional variability in T2D and related risk factors is important for the planning of diabetes prevention programs. In our analyses, common lifestyle factors did not nearly explain these variations between the northern SHIP-TREND and the southern KORA-F4 studies. Further examinations of regional socioeconomic, political, environmental and other aspects are needed. Meanwhile, targeted diabetes prevention strategies with a special focus on men living in the northern parts of Germany are reasonable. PMID- 27275748 TI - Association between anti-Mullerian hormone and insulin resistance in non-obese adolescent females with polycystic ovary syndrome. AB - OBJECTIVE: The present study was designed to evaluate the association between anti-Mullerian hormone (AMH) and insulin resistance (IR) in non-obese adolescent females with polycystic ovary syndrome (PCOS) with and without IR. METHODS: Seventy-seven consecutive non-obese patients were recruited and distributed into three groups according to diagnoses of PCOS and IR. Group I included 27 females diagnosed with PCOS and IR, group II included 18 females diagnosed with PCOS but without IR, and group III included 32 controls without PCOS. RESULTS: Group I had significantly higher AMH levels compared to group II and group III (p < 0.012 and p < 0.000, respectively). ROC curve analyses demonstrated that the AUC, indicative of the AMH value for discriminating PCOS with IR, was 0.763, with a confidence interval of 0.607-0.920 (p = 0.004). There was a significant positive correlation between serum AMH and HOMA-IR levels in adolescent females with PCOS (p = 0.003). CONCLUSION: We found that serum AMH levels were higher in non-obese adolescent females with PCOS and IR than in PCOS patients without IR and the healthy controls. There was a significant positive correlation between AMH levels and IR in non-obese adolescent females with PCOS. PMID- 27275747 TI - Immunoregulatory Effects of Everolimus on In Vitro Alloimmune Responses. AB - Everolimus (EVL) is a novel mTOR-inhibitor similar to sirolimus (SRL) that is used in organ transplant recipients, often in combination with tacrolimus (TAC) or mycophenolate (MPA). The current study aims to determine its effects on regulatory T cells. Increasing concentrations of EVL, MPA and TAC alone or in combination were added to MLRs of healthy volunteers. Lymphoproliferation by 3H TdR incorporation and the percentage of newly generated CD4+CD127-CD25+FOXP3+ (total Treg) and CD4+CD127-CD25HighFOXP3+ (natural Treg) in CFSE labeled responder cells were assessed by flow cytometry. In comparison to medium controls, EVL and other agents dose-dependently inhibited 3H-TdR incorporation in HLA-2DR-matched and HLA-mismatched MLRs (n = 3-10). However, EVL significantly amplified newly generated total and natural Tregs in CFSE labeled responder cells (p<0.05) at all concentrations, while MPA and SRL did this only at sub therapeutic concentrations and inhibited at therapeutic levels. In contrast, TAC inhibited newly generated Tregs at all concentrations. When tested in combination with TAC, EVL failed to reverse TAC inhibition of Treg generation. Combinations of EVL and low concentrations of MPA inhibited proliferation and amplified Treg generation in an additive manner when compared to medium controls or each drug tested alone (p<0.05). The relative tolerogenic effect from high to low was EVL > SRL> MPA > TAC. If the results from these in vitro studies are extrapolated to clinical transplantation, it would suggest EVL plus low concentrations of MPA may be the most tolerogenic combination. PMID- 27275757 TI - From Kondo lattices to Kondo superlattices. AB - The realization of new classes of ground states in strongly correlated electron systems continues to be a major issue in condensed matter physics. Heavy fermion materials, whose electronic structure is essentially three-dimensional, are one of the most suitable systems for obtaining novel electronic states because of their intriguing properties associated with many-body effects. Recently, a state of-the-art molecular beam epitaxy technique was developed to reduce the dimensionality of heavy electron systems by fabricating artificial superlattices that include heavy fermion compounds; this approach can produce a new type of electronic state in two-dimensional (2D) heavy fermion systems. In artificial superlattices of the antiferromagnetic heavy fermion compound CeIn3 and the conventional metal LaIn3, the magnetic order is suppressed by a reduction in the thickness of the CeIn3 layers. In addition, the 2D confinement of heavy fermions leads to enhancement of the effective electron mass and deviation from the standard Fermi liquid electronic properties, which are both associated with the dimensional tuning of quantum criticality. In the superconducting superlattices of the heavy fermion superconductor CeCoIn5 and nonmagnetic metal YbCoIn5, signatures of superconductivity are observed even at the thickness of one unit cell layer of CeCoIn5. The most remarkable feature of this 2D heavy fermion superconductor is that the thickness reduction of the CeCoIn5 layers changes the temperature and angular dependencies of the upper critical field significantly. This result is attributed to a substantial suppression of the Pauli pair-breaking effect through the local inversion symmetry breaking at the interfaces of CeCoIn5 block layers. The importance of the inversion symmetry breaking in this system has also been supported by site-selective nuclear magnetic resonance spectroscopy, which can resolve spectroscopic information from each layer separately, even within the same CeCoIn5 block layer. In addition, recent experiments involving CeCoIn5/YbCoIn5 superlattices have shown that the degree of the inversion symmetry breaking and, in turn, the Rashba splitting are controllable, offering the prospect of achieving even more fascinating superconducting states. Thus, these Kondo superlattices pave the way for the exploration of unconventional metallic and superconducting states. PMID- 27275756 TI - Bronchus-associated Lymphoid Tissue in Kabuki Syndrome with Associated Hyper-IgM Syndrome/Common Variable Immunodeficiency. PMID- 27275758 TI - [Not Available]. PMID- 27275759 TI - Polyvinyl alcohol-graft-polyethylene glycol hydrogels improve utility and biofunctionality of injectable collagen biomaterials. AB - Collagen-based materials have become a staple in both research and the clinic. In wound care, collagen-based materials comprise a core gamut of biological dressings and therapeutic strategies. In research, collagen-based materials are employed in everything from 3D cultures to bioprinting. Soluble collagen is well characterized to undergo fibrillation at neutral pH and 37 degrees C. To remain stable, a neutralized collagen solution must be maintained at 4 degrees C. These physical characteristics of collagen impose limitations on its utility. In our previous work, we identified that the incorporation of a simple polyvinyl alcohol:borate hydrogel could improve the rate of collagen gel fibrillation. In this work we sought to further investigate the interactions of polyvinyl alcohol blend variants, as surfactant-like polymers, in comparison with known non-polymer surfactants. To conduct our investigations scaffold variants were created using increasing concentrations of polyvinyl alcohol, differing combinations of polymers, and non-polymer surfactants Tweens 20 and 80, and TritonX-100. Activation energy for collagen fibrillation was found to significantly decrease in the presence of polyvinyl alcohols (p < 0.01) at and above 0.4%w/v concentration. Further, addition of polyvinyl alcohol-graft-polyethylene glycol had the greatest enhancement (2.02 fold) on the fibrillation kinetics (p < 0.01), wetting properties and the stability of the collagen scaffolds post-freeze drying. Our results demonstrated that the addition of polyvinyl alcohol hydrogels to a collagen solution could stabilize collagen solution such that the solution could easily be lyophilized (at pH 7) and then reconstituted with water. Cells cultured in polyvinyl alcohol scaffolds also exhibited more organized F-actin, as well as a reduced abundance of pro-collagen and alpha-smooth actin. In conclusion, our results demonstrate for the first time that polyvinyl alcohol, preferably polyvinyl alcohol-graft-polyethylene glycol, directly affects the physical properties of collagen and the physiology of cells cultured within improving the utility of the combined material for both research and clinic needs. PMID- 27275760 TI - Metabolites of the Polycyclic Aromatic Hydrocarbon Phenanthrene in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer. AB - Results from the Multiethnic Cohort Study demonstrated significant differences in lung cancer risk among cigarette smokers from five different ethnic/racial groups. For the same number of cigarettes smoked, and particularly among light smokers, African Americans and Native Hawaiians had the highest risk for lung cancer, Whites had intermediate risk, while Latinos and Japanese Americans had the lowest risk. We analyzed urine samples from 331-709 participants from each ethnic group in this study for metabolites of phenanthrene, a surrogate for carcinogenic polycyclic aromatic hydrocarbon exposure. Consistent with their lung cancer risk and our previous studies of several other carcinogens and toxicants of cigarette smoke, African Americans had significantly (p<0.0001) higher median levels of the two phenanthrene metabolites 3-hydroxyphenanthrene (3-PheOH, 0.931 pmol/ml) and phenanthrene tetraol (PheT, 1.13 pmol/ml) than Whites (3-PheOH, 0.697 pmol/ml; PheT, 0.853 pmol/ml) while Japanese-Americans had significantly (p = 0.002) lower levels of 3-PheOH (0.621 pmol/ml) than Whites. PheT levels (0.838 pmol/ml) in Japanese-Americans were not different from those of Whites. These results are mainly consistent with the lung cancer risk of these three groups, but the results for Native Hawaiians and Latinos were more complex. We also carried out a genome wide association study in search of factors that could influence PheT and 3-PheOH levels. Deletion of GSTT1 explained 2.2% of the variability in PheT, while the strongest association, rs5751777 (p = 1.8x10-62) in the GSTT2 gene, explained 7.7% of the variability in PheT. These GWAS results suggested a possible protective effect of lower GSTT1 copy number variants on the diol epoxide pathway, which was an unexpected result. Collectively, the results of this study provide further evidence that different patterns of cigarette smoking are responsible for the higher lung cancer risk of African Americans than of Whites and the lower lung cancer risk of Japanese Americans, while other factors appear to be involved in the differing risks of Native Hawaiians and Latinos. PMID- 27275762 TI - Extracorporeal Membrane Oxygenation for Acute Cardiogenic Shock: How Do You Mend a Broken Heart? PMID- 27275761 TI - Human MiR-544a Modulates SELK Expression in Hepatocarcinoma Cell Lines. AB - Hepatocellular carcinoma (HCC) is a multi-factorial cancer with a very poor prognosis; therefore, there are several investigations aimed at the comprehension of the molecular mechanisms leading to development and progression of HCC and at the definition of new therapeutic strategies. We have recently evaluated the expression of selenoproteins in HCC cell lines in comparison with normal hepatocytes. Recent results have shown that some of them are down- and others up regulated, including the selenoprotein K (SELK), whose expression was also induced by sodium selenite treatment on cells. However, so far very few studies have been dedicated to a possible effect of microRNAs on the expression of selenoproteins and their implication in HCC. In this study, the analysis of SELK 3'UTR by bioinformatics tools led to the identification of eight sites potentially targeted by human microRNAs. They were then subjected to a validation test based on luciferase reporter constructs transfected in HCC cell lines. In this functional screening, miR-544a was able to interact with SELK 3'UTR suppressing the reporter activity. Transfection of a miR-544a mimic or inhibitor was then shown to decrease or increase, respectively, the translation of the endogenous SELK mRNA. Intriguingly, miR-544a expression was found to be modulated by selenium treatment, suggesting a possible role in SELK induction by selenium. PMID- 27275763 TI - Correction: Underweight, Markers of Cachexia, and Mortality in Acute Myocardial Infarction: A Prospective Cohort Study of Elderly Medicare Beneficiaries. AB - This article was republished on May 19th, 2016 to correct poor figure quality in the PDF version, which was introduced during the typesetting process. [This corrects the article DOI: 10.1371/journal.pmed.1001998.]. PMID- 27275764 TI - Structures of KdnB and KdnA from Shewanella oneidensis: Key Enzymes in the Formation of 8-Amino-3,8-Dideoxy-d-Manno-Octulosonic Acid. AB - 8-Amino-3,8-dideoxy-d-manno-octulosonic acid (Kdo8N) is a unique amino sugar that has thus far only been observed on the lipopolysaccharides of marine bacteria belonging to the genus Shewanella. Although its biological function is still unclear, it is thought that the sugar is important for the integrity of the bacterial cell outer membrane. A three-gene cluster required for the biosynthesis of Kdo8N was first identified in Shewanella oneidensis. Here we describe the three-dimensional structures of two of the enzymes required for Kdo8N biosynthesis in S. oneidensis, namely, KdnB and KdnA. The structure of KdnB was solved to 1.85-A resolution, and its overall three-dimensional architecture places it into the Group III alcohol dehydrogenase superfamily. A previous study suggested that KdnB did not require NAD(P) for activity. Strikingly, although the protein was crystallized in the absence of any cofactors, the electron density map clearly revealed the presence of a tightly bound NAD(H). In addition, a bound metal was observed, which was shown via X-ray fluorescence to be a zinc ion. Unlike other members of the Group III alcohol dehydrogenases, the dinucleotide cofactor in KdnB is tightly bound and cannot be removed without leading to protein precipitation. With respect to KdnA, it is a pyridoxal 5'-phosphate or (PLP)-dependent aminotransferase. For this analysis, the structure of KdnA, trapped in the presence of the external aldimine with PLP and glutamate, was determined to 2.15-A resolution. The model of KdnA represents the first structure of a sugar aminotransferase that functions on an 8-oxo sugar. Taken together the results reported herein provide new molecular insight into the biosynthesis of Kdo8N. PMID- 27275765 TI - Assessment of ghrelin, leptin, orexin A and alpha-MSH serum concentrations and the levels of the autoantibodies against the aforementioned peptides in relation to Helicobacter pylori infections and Candida albicans colonization in children with short stature. PMID- 27275766 TI - [Body mass and body length of warsaw's newborns]. PMID- 27275767 TI - [Screening in specific categories of neonates exposed to congenital hypothyroidism]. PMID- 27275768 TI - [The treatment and monitoring of the therapy of congenital hypothyroidism]. PMID- 27275769 TI - Zespol Silvera-Rusella. Czesc II. PMID- 27275770 TI - [Dental abnormalities and orthodontic disorders in Turner's syndrome patients]. PMID- 27275771 TI - Syncope is a frequently under-diagnosed condition in infants and toddlers and has similar features to those seen in adolescents and adults. AB - AIM: Vagal syncope may not be readily recognised by the caregivers of younger children, often leading to extensive diagnostic evaluation. Our aim was to determine the characteristics of syncope in younger children and to assess whether this age group was more prone to undergoing extensive diagnostic work-ups and receiving wrong aetiological diagnoses. METHODS: We collected clinical data on children up to six years of age, referred to our paediatric neurology clinic between 2007 and 2014 following one or more episodes of sudden loss of consciousness. RESULTS: A family history of syncope was present in 59.5% of the 37 children, and a trigger for syncope was identified in 30 children. Most of the episodes were short, with witnesses reporting an immediate or quick recovery. Most of the children underwent diagnostic procedures, particularly an electroencephalogram, and all the results were normal. Epilepsy did not develop in any of these cases. Syncope recurred in 22 patients during a two-year follow up. CONCLUSION: Vagal syncope had similar features in toddlers and young children to those seen in adolescents and adults. Its diagnosis should be considered following loss of consciousness due to an identifiable trigger and rapidly regaining consciousness to avoid unnecessary diagnostic procedures and hospitalisation. PMID- 27275772 TI - Predicting the Risk of Melanoma. PMID- 27275773 TI - Chronic administration tetrahydroxystilbene glucoside promotes hippocampal memory and synaptic plasticity and activates ERKs, CaMKII and SIRT1/miR-134 in vivo. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Polygonum multiflorum Thunb is a traditional Chinese medicine with anti-aging effect. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D glucoside (TSG) is generally considered as the main active component in Polygonum multiflorum Thunb. However, the effect of TSG on memory in adult is unclear till now. AIM OF STUDY: 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG) is a polyphenols compound from Polygonum multiflorum Thunb. The present study aimed to evaluate the effect of chronic administration of TSG on hippocampal memory in normal mice. MATERIALS AND METHODS: Behavioral test, electrophysiology and golgi staining were used to evaluate the effect of TSG on hippocampus-dependent memory and synaptic plasticity. Western blotting was used to determine the expression of ERK1/2, CaMKII, and SIRT1. Real-time quantitative PCR was explored to measure miR 134. RESULTS: It was found that TSG enhanced hippocampus-dependent contextual fear memory and novel object recognition, facilitated hippocampal LTP and increased dendrite spine density in the CA1 region of hippocampus. TSG obviously promoted the phosphorylations of ERK1/2, CaMKII, CREB and the expression of BDNF in the hippocampus, with upregulation of silent information regulator 1 (SIRT1) and downregulation of miR-134. CONCLUSIONS: Chronic administration of TSG promotes hippocampal memory in normal mice, suggesting that supplementary of TSG might serve as an enhancement of memory. PMID- 27275774 TI - BACE1 molecular docking and anti-Alzheimer's disease activities of ginsenosides. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenosides are natural product steroid glycosides and triterpene saponins obtained from the Panax species. Panax ginseng has been widely used as a traditional Chinese medicine (TCM) for around a thousand years, especially in East Asian countries. Ginseng, the root and rhizome of the most popular species P. ginseng, used as tonic, prophylactic agent and restorative. In TCM, ginseng is highly valued herb and has been applied to a variety of pathological conditions and illnesses such as hypodynamia, anorexia, shortness of breath, palpitation, insomnia, impotence, hemorrhage and diabetes. AIM OF THE STUDY: The basic aim of this study was to evaluate the anti Alzheimer's disease activities of selected ginsenosides (Rb1, Rb2, Rc, Re, Rg1, and Rg3) according to peroxynitrite (ONOO(-)) scavenging activity and inhibitory activity of ONOO(-)-mediated nitrotyrosine formation as a measure of changes in oxidative stress. In addition, molecular docking simulation studies were performed to predict binding energies of the ginsenosides with beta-site amyloid precursor protein cleaving enzyme 1 (BACE1, beta-secretase) and identify the interacting residues. MATERIALS AND METHODS: In vitro cholinesterase enzyme assays by using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1 were performed. In vitro authentic peroxynitrite scavenging activity and inhibitory activity against ONOO(-)-mediated nitrotyrosine formation were also performed. Molecular docking simulation studies were performed with Autodock Vina software and Discovery studio 4.1. RESULTS: In vitro enzyme assays demonstrated that ginsenosides have significant inhibitory potential against AChE, BChE, and BACE1, as well as ONOO(-) and nitrotyrosine formation. Most importantly, significant AChE inhibitory activities were observed for Re; BChE for Rg3; and BACE1 for Rc, with IC50 values of 29.86+/-3.20, 16.80+/-0.36, and 59.81+/ 2.74MUg/mL, respectively. Among the tested ginsenosides, Rb1 exhibited a higher scavenging activity against ONOO(-) with an IC50 value of 27.86+/-1.34MUg/mL, while Rc and Rg3 exhibited impressive inhibitory activity against the formation of nitrotyrosine. In addition, molecular docking studies revealed potential BACE1 inhibitory activity of ginsenosides, especially Rb1 and Rb2, which exhibited good binding affinities towards BACE1, with docking scores of -10kcal/mol. CONCLUSION: The findings of the present study suggest the potential of ginsenosides (Rb1, Rb2, Rc, Re, Rg1, and Rg3) for use in the development of therapeutic or preventive agents for Alzheimer's disease, especially through inhibition of AChE, BChE and BACE1 activities, as well as scavenging of ONOO(-) and inhibition of nitrotyrosine formation. PMID- 27275775 TI - Guanylate binding protein 5: Impairing virion infectivity by targeting retroviral envelope glycoproteins. AB - Guanylate binding proteins (GBPs) are interferon-inducible cellular factors that belong to the superfamily of guanosine triphosphatases (GTPases) and play important roles in the cell-intrinsic defense against bacteria, protozoa and viruses. In a recent report in Cell Host & Microbe, we identify GBP5 as novel restriction factor of HIV-1 that reduces the infectivity of progeny virions by interfering with processing and incorporation of the viral envelope (Env) glycoprotein. The inhibitory activity of GBP5 requires C-terminal isoprenylation, mediating Golgi-association, but not its GTPase function. Notably, GBP5 expression levels vary considerably in human macrophages and inversely correlate with infectious virus yield. We demonstrate that GBP5 can be evaded by an unusual tradeoff mechanism: Naturally occurring mutations in the start codon of the viral accessory gene vpu attenuate GBP5 inhibition by increasing Env expression at the cost of Vpu function. Whether direct counteraction mechanisms or more subtle changes balancing Vpu and Env expression also affect HIV-1 inhibition by GBP5 remains to be clarified. Other open questions are whether GBP5 restricts HIV-1 in CD4+ T cells and if other GBP family members also decrease infectivity of HIV and/or additional enveloped viruses. PMID- 27275776 TI - Electromagnetic fields and anomalous transports in heavy-ion collisions-a pedagogical review. AB - The hot and dense matter generated in heavy-ion collisions may contain domains which are not invariant under P and CP transformations. Moreover, heavy-ion collisions can generate extremely strong magnetic fields as well as electric fields. The interplay between the electromagnetic field and triangle anomaly leads to a number of macroscopic quantum phenomena in these P- and CP-odd domains known as anomalous transports. The purpose of this article is to give a pedagogical review of various properties of the electromagnetic fields, the anomalous transport phenomena, and their experimental signatures in heavy-ion collisions. PMID- 27275777 TI - Survey of Intraocular Antibiotics Prophylaxis Practice after Open Globe Injury in China. AB - PURPOSE: To elucidate the Chinese practice of intraocular antibiotics administration for prophylaxis after open globe injury. METHODS: A cross sectional questionnaire survey was performed online by scanning a Quickmark (QR) code with smartphones at the 20th Chinese National Conference of Ocular Trauma in November 2014. RESULTS: A total of 153 (30.6%) of all participators at the conference responded. Of the respondents, 20.9% were routinely administered with prophylactic intraocular injection of antibiotics at the conclusion of the primary eye repair, and 56.9% were used only in cases with high risk of endophthalmitis development. The intraocular route of delivery was mainly included with intracameral injection (47.9%) and intravitreal injection (42.0%). Cephalosporins (53.8%) and vancomycin (42.0%) were the main choices of antibiotic agents, followed by fluoroquinolones (24.3%), and aminoglycosides (13.4%). Only 21.9% preferred a combination of two or more two drugs routinely. In addition, significantly more respondents from the referral eye hospital (92.7%) replied using intraocular antibiotics injection for prophylaxis compared to those respondents from the primary hospital (69.4%) (p = 0.001, Fisher's exact test). CONCLUSIONS: Intraocular antibiotics injection for post-traumatic endophthalmitis prophylaxis is widely used in China. However, the choice of antibiotic agents and the intraocular route of delivery vary. A well-designed clinical trial is needed to establish a standardized protocol of intraocular antibiotics administration for post-traumatic endophthalmitis prophylaxis. PMID- 27275778 TI - Inflammatory and Immune Responses to Surgery and Their Clinical Impact. AB - OBJECTIVE: The aim of this study was to describe current understanding of the local and systemic immune responses to surgery and their impact on clinical outcomes, predictive biomarkers, and potential treatment strategies. BACKGROUND: Patients undergoing major surgery are at risk of life-threatening inflammatory complications that include infection, the systemic inflammatory response syndrome (SIRS), or sepsis. Although improvements in surgical technique and peri-operative care have resulted in reduction in the rates of these complications, they remain high, especially in patients undergoing complex abdominal procedures. There are currently no drugs licensed specifically for the treatment of sepsis nor is it possible to identify those at highest risk, which would allow pre-emptive therapy that may improve outcomes. CONCLUSIONS: Local immune responses to surgery lead to systemic pro-inflammatory and immunosuppressive phases that are temporally related and proportionate in magnitude. Improved understanding of these mechanisms has implications for clinical study design and has led to the emergence of novel biomarkers such as Toll-like receptor expression. These can be used to stratify patient care pathways to maximize the benefit from current therapies or to select the right target at the right phase of illness for future drug development. PMID- 27275779 TI - Arterial Transit Time Mapping Obtained by Pulsed Continuous 3D ASL Imaging with Multiple Post-Label Delay Acquisitions: Comparative Study with PET-CBF in Patients with Chronic Occlusive Cerebrovascular Disease. AB - Arterial transit time (ATT) is most crucial for measuring absolute cerebral blood flow (CBF) by arterial spin labeling (ASL), a noninvasive magnetic resonance (MR) perfusion assessment technique, in patients with chronic occlusive cerebrovascular disease. We validated ASL-CBF and ASL-ATT maps calculated by pulsed continuous ASL (pCASL) with multiple post-label delay acquisitions in patients with occlusive cerebrovascular disease. Fifteen patients underwent MR scans, including pCASL, and positron emission tomography (PET) scans with 15O water to obtain PET-CBF. MR acquisitions with different post-label delays (1.0, 1.5, 2.0, 2.5 and 3.0 sec) were also obtained for ATT correction. The theoretical framework of 2-compartmental model (2CM) was also used for the delay compensation. ASL-CBF and ASL-ATT were calculated based on the proposed 2CM, and the effect on the CBF values and the ATT correction characteristics were discussed. Linear regression analyses were performed both on pixel-by-pixel and region-of-interest bases in the middle cerebral artery (MCA) territory. There were significant correlations between ASL-CBF and PET-CBF both for voxel values (r = 0.74 +/- 0.08, slope: 0.87 +/- 0.22, intercept: 6.1 +/- 4.9) and for the MCA territorial comparison in both affected (R2 = 0.67, y = 0.83x + 6.3) and contralateral sides (R2 = 0.66, y = 0.74x + 6.3). ASL-ATTs in the affected side were significantly longer than those in the contralateral side (1.51 +/- 0.41 sec and 1.12 +/- 0.30 sec, respectively, p <0.0005). CBF measurement using pCASL with delay compensation was feasible and fairly accurate even in altered hemodynamic states. PMID- 27275780 TI - NrdR Transcription Regulation: Global Proteome Analysis and Its Role in Escherichia coli Viability and Virulence. AB - Bacterial ribonucleotide reductases (RNRs) play an important role in the synthesis of dNTPs and their expression is regulated by the transcription factors, NrdR and Fur. Recent transcriptomic studies using deletion mutants have indicated a role for NrdR in bacterial chemotaxis and in the maintenance of topoisomerase levels. However, NrdR deletion alone has no effect on bacterial growth or virulence in infected flies or in human blood cells. Furthermore, transcriptomic studies are limited to the deletion strain alone, and so are inadequate for drawing biological implications when the NrdR repressor is active or abundant. Therefore, further examination is warranted of changes in the cellular proteome in response to both NrdR overexpression, as well as deletion, to better understand its functional relevance as a bacterial transcription repressor. Here, we profile bacterial fate under conditions of overexpression and deletion of NrdR in E. coli. Biochemical assays show auxiliary zinc enhances the DNA binding activity of NrdR. We also demonstrate at the physiological level that increased nrdR expression causes a significant reduction in bacterial growth and fitness even at normal temperatures, and causes lethality at elevated temperatures. Corroborating these direct effects, global proteome analysis following NrdR overexpression showed a significant decrease in global protein expression. In parallel, studies on complementary expression of downregulated essential genes polA, eno and thiL showed partial rescue of the fitness defect caused by NrdR overexpression. Deletion of downregulated non-essential genes ygfK and trxA upon NrdR overexpression resulted in diminished bacterial growth and fitness suggesting an additional role for NrdR in regulating other genes. Moreover, in comparison with NrdR deletion, E. coli cells overexpressing NrdR showed significantly diminished adherence to human epithelial cells, reflecting decreased bacterial virulence. These results suggest that elevated expression of NrdR could be a suitable means to retard bacterial growth and virulence, as its elevated expression reduces bacterial fitness and impairs host cell adhesion. PMID- 27275781 TI - Joint Effects: A Pilot Investigation of the Impact of Bipolar Disorder and Marijuana Use on Cognitive Function and Mood. AB - Marijuana is the most widely used illicit substance in those diagnosed with bipolar I disorder. However, there is conflicting evidence as to whether marijuana may alleviate or exacerbate mood symptomatology. As bipolar disorder and marijuana use are individually associated with cognitive impairment, it also remains unclear whether there is an additive effect on cognition when bipolar patients use marijuana. The current study aimed to determine the impact of marijuana on mood in bipolar patients and to examine whether marijuana confers an additional negative impact on cognitive function. Twelve patients with bipolar disorder who smoke marijuana (MJBP), 18 bipolar patients who do not smoke (BP), 23 marijuana smokers without other Axis 1 pathology (MJ), and 21 healthy controls (HC) completed a neuropsychological battery. Further, using ecological momentary assessment, participants rated their mood three times daily as well as after each instance of marijuana use over a four-week period. Results revealed that although the MJ, BP, and MJBP groups each exhibited some degree of cognitive impairment relative to HCs, no significant differences between the BP and MJBP groups were apparent, providing no evidence of an additive negative impact of BPD and MJ use on cognition. Additionally, ecological momentary assessment analyses indicated alleviation of mood symptoms in the MJBP group after marijuana use; MJBP participants experienced a substantial decrease in a composite measure of mood symptoms. Findings suggest that for some bipolar patients, marijuana may result in partial alleviation of clinical symptoms. Moreover, this improvement is not at the expense of additional cognitive impairment. PMID- 27275782 TI - 18O-Tracer Metabolomics Reveals Protein Turnover and CDP-Choline Cycle Activity in Differentiating 3T3-L1 Pre-Adipocytes. AB - The differentiation of precursor cells into mature adipocytes (adipogenesis) has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell line is the most well characterized cellular model of adipogenesis. Using a time course metabolomics approach, we show that the 3T3-L1 preadipocyte metabolome is greatly altered during the first 48 hours of differentiation, where cells go through about two rounds of cell division, a process known as mitotic clonal expansion. Short-chain peptides were among several small molecules that were increased during mitotic clonal expansion. Additional indicators of protein turnover were also increased, including bilirubin, a degradation product of heme-containing proteins, and 3 methylhistidine, a post-translationally modified amino acid that is not reutilized for protein synthesis. To study the origin of the peptides, we treated differentiating preadipocytes with 18O labeled water and found that 18O was incorporated into the short chain peptides, confirming them, at least in part, as products of hydrolysis. Inhibitors of the proteasome or matrix metalloproteinases affected the peptide levels during differentiation, but inhibitors of autophagy or peptidases did not. 18O was also incorporated into several choline metabolites including cytidine 5'-diphosphocholine (CDP-choline), glycerophosphocholine, and several phosphatidylcholine species, indicative of phosphatidylcholine synthesis/degradation and of flux through the CDP-choline cycle, a hallmark of proliferating cells. 18O-Tracer metabolomics further showed metabolic labeling of glutamate, suggestive of glutaminolysis, also characteristic of proliferating cells. Together, these results highlight the utility of 18O isotope labeling in combination with metabolomics to uncover changes in cellular metabolism that are not detectable by time-resolved metabolomics. PMID- 27275784 TI - Late Pleistocene/Early Holocene Migratory Behavior of Ungulates Using Isotopic Analysis of Tooth Enamel and Its Effects on Forager Mobility. AB - Zooarchaeological and paleoecological investigations have traditionally been unable to reconstruct the ethology of herd animals, which likely had a significant influence on the mobility and subsistence strategies of prehistoric humans. In this paper, we reconstruct the migratory behavior of red deer (Cervus elaphus) and caprids at the Pleistocene-Holocene transition in the northeastern Adriatic region using stable oxygen isotope analysis of tooth enamel. The data show a significant change in delta18O values from the Pleistocene into the Holocene, as well as isotopic variation between taxa, the case study sites, and through time. We then discuss the implications of seasonal faunal availability as determining factors in human mobility patterns. PMID- 27275783 TI - Terpinen-4-ol: A Novel and Promising Therapeutic Agent for Human Gastrointestinal Cancers. AB - BACKGROUND: Terpinen-4-ol, a naturally occurring monoterpene is the main bioactive component of tea-tree oil and has been shown to have many biological activities. AIM: To study the antitumor effects of terpinen-4-ol and its mechanism of action in prostate and GI malignancies, alone and in combination with chemotherapeutic and biological agents. METHODS: Terpinen-4-ol was administrated alone or combined with standard chemotherapy (Oxaliplatin, Fluorouracil, Gemcitabine, Tarceva) and biological agent (Cetuximab). It was also combined with humanized anti-CD24 mAbs (was developed by us). Killing effects were measured qualitatively by light microscopy and quantitatively using the MTT and FACS analysis, following treatment of colorectal, pancreatic, gastric and prostate cancer cells. Terpinen-4-ol effect on tumor development was evaluated in xenograft model. RESULTS: Terpinen-4-ol induces a significant growth inhibition of colorectal, pancreatic, prostate and gastric cancer cells in a dose-dependent manner (10-90% in 0.005-0.1%). Terpinen-4-ol and various anti-cancer agents (0.2MUM oxaliplatin and 0.5MUM fluorouracil) demonstrated a synergistic inhibitory effect (83% and 91%, respectively) on cancer cell proliferation. In KRAS mutated colorectal cancer cells, which are resistant to anti-EGFR therapy, combining of terpinen-4-ol with cetuximab (1 MUM) resulted in impressive efficacy of 80-90% growth inhibition. Sub-toxic concentrations of terpinen-4-ol potentiate anti-CD24 mAb (150MUg/ml)-induced growth inhibition (90%). Considerable reduction in tumor volume was seen following terpinen-4-ol (0.2%) treatment alone and with cetuximab (10mg/kg) (40% and 63%, respectively) as compare to the control group. CONCLUSION: Terpinen-4-ol significantly enhances the effect of several chemotherapeutic and biological agents. The possible molecular mechanism for its activity involves induction of cell-death rendering this compound as a potential anti-cancer drug alone and in combination in the treatment of numerous malignancies. Terpinen-4-ol restores the activity of cetuximab in cancers with mutated KRAS. PMID- 27275785 TI - Further development of biomarkers in amyotrophic lateral sclerosis. AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an idiopathic neurodegenerative disease usually fatal in less than three years. Even if standard guidelines are available to diagnose ALS, the mean diagnosis delay is more than one year. In this context, biomarker discovery is a priority. Research has to focus on new diagnostic tools, based on combined explorations. AREAS COVERED: In this review, we specifically focus on biology and imaging markers. We detail the innovative field of 'omics' approach and imaging and explain their limits to be useful in routine practice. We describe the most relevant biomarkers and suggest some perspectives for biomarker research. Expert commentary: The successive failures of clinical trials in ALS underline the need for new strategy based on innovative tools to stratify patients and to evaluate their responses to treatment. Biomarker data may be useful to improve the designs of clinical trials. Biomarkers are also needed to better investigate disease pathophysiology, to identify new therapeutic targets, and to improve the performance of clinical assessments for diagnosis and prognosis in the clinical setting. A consensus on the best management of neuroimaging and 'omics' methods is necessary and a systematic independent validation of findings may add robustness to future studies. PMID- 27275786 TI - Aneuploidy Screening in Pregnancy. AB - Prenatal aneuploidy screening has changed dramatically in recent years with increases in the types of chromosomal abnormalities reliably identified and in the proportion of aneuploid fetuses detected. Initially, screening was available only for trisomies 21 and 18 and was offered only to low-risk pregnancies. Improved detection with the quadruple- and first-trimester multiple marker screens led to the option of aneuploidy screening for women 35 years of age and older. Cell-free DNA tests now screen for common autosomal trisomies and sex chromosome aneuploidies. Cell-free DNA screening is particularly effective in older women because of higher positive predictive values and lower false-positive rates. Integrated first- and second-trimester multiple marker tests provide specific risks for trisomies 21, 18, and possibly 13, and may detect an even wider range of aneuploidies. Given current precision in risk assessment, based on maternal age and preferences for screening or diagnostic tests, counseling has become more complex. This review addresses the benefits and limitations of available aneuploidy screening methods along with counseling considerations when offering them. PMID- 27275788 TI - The Accuracy of Web Sites and Cellular Phone Applications in Predicting the Fertile Window. AB - OBJECTIVE: To evaluate the validity of fertility web sites and applications (apps) by comparing the predicted fertile window of these modalities to the actual fertile window of a standard 28-day cycle. METHODS: This was a descriptive study. The top resulting free web sites and electronic apps downloadable to a cellular phone that provide calendars for fertility and ovulation prediction were assessed. Cycles were standardized to 28 days in length, 4 days of menses, and the last menstrual period was set to January 1, 2015. The predicted date of ovulation and fertility window generated were compared with an actual estimated date of ovulation on cycle day 15, January 15, and a fertile window consisting of cycle day 10 to cycle day 15, the day of ovulation plus the preceding 5 cycle days, January 10-15. RESULTS: Data from 20 web sites and 33 apps were collected. Of all the web sites and apps used, one web site and three apps predicted the precise fertile window. CONCLUSION: Web sites and electronic apps used by the general public to predict fertile windows are generally inaccurate, although the clinical effect of this inaccuracy is unknown. Although they all include the most fertile cycle day, the range of the fertility window varies widely. Patients who are trying to conceive with the assistance of calendars generated from web sites and electronic apps should be counseled on the inaccuracy of these modalities. PMID- 27275787 TI - Variation in Postpartum Glycemic Screening in Women With a History of Gestational Diabetes Mellitus. AB - OBJECTIVE: To assess patterns and predictors of postpartum diabetes screening in a commercially insured, geographically and sociodemographically diverse sample of women with gestational diabetes mellitus. METHODS: Using commercial insurance claims (2000-2012) from all 50 states, we conducted a retrospective cohort study in 447,556 women with at least one delivery and continuous enrollment 1 year before and after delivery. We identified women with a gestational diabetes mellitus pregnancy and examined postpartum diabetes screening type and timing and performed logistic regression to identify screening predictors. RESULTS: Gestational diabetes mellitus was diagnosed in 32,253 (7.2%) women during the study timeframe. Three fourths received no screening within 1 year postpartum. Rates of recommended 75-g oral glucose tolerance testing within 6-12 weeks were low but increased over time (27 [2%] in 2001 compared with 249 [7%] in 2011, adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 2.0-47). Among women screened, those in the Northeast (19%) and South (18%) were least likely to receive a 75-g oral glucose tolerance test within 0-12 weeks (adjusted OR 0.4 for each, CI 0.4-0.5) compared with the West (36%). Asian women were most likely to receive any screening (18%; adjusted OR 1.5, CI 1.3-1.6) compared with white women (12%). Black women were most likely to receive hemoglobin A1c (21%; adjusted OR 2.0, CI 1.3-3.2) compared with white women (11%). Antepartum antiglycemic medication (21%; adjusted OR 2.1, CI 2.0-2.3) or visit to a nutritionist-diabetes educator (19%; adjusted OR 1.6, CI 1.4-1.7) or endocrinologist (23%; adjusted OR 1.7, CI 1.6-1.9) predicted screening within 12 weeks postpartum. CONCLUSION: Postpartum diabetes screening remains widely underused among commercially insured women with gestational diabetes mellitus. Differences in screening by geography, race, and antepartum care can inform health system and public health interventions to increase diabetes detection in this high-risk population. PMID- 27275789 TI - Association of Sexual Debut in Adolescents With Microbiota and Inflammatory Markers. AB - OBJECTIVE: To investigate the association of sexual debut and vaginal, anorectal, and oral microbiota and vaginal inflammatory markers in female adolescents. METHODS: We conducted a school-based study in adolescents in Antwerp, Belgium. During three visits over 8 months, participants answered questionnaires and self collected vaginal, anorectal, and oral swabs. Five Lactobacillus species, Lactobacillus genus, Gardnerella vaginalis, and Atopobium vaginae were quantified; and seven inflammatory markers were measured in the vaginal specimens. In the oral and anorectal specimens, Lactobacillus genus, G vaginalis, and A vaginae were ascertained. RESULTS: Of the 93 adolescents (mean age 16.2 years) at the first visit, 41 (44.1%) had passed sexual debut (penile-vaginal intercourse) and five (5.4%) had sexual experience without passing sexual debut. Having sexual experience at the first visit was not found to be associated with species presence or concentrations (acknowledging an underpowered study because the required sample size was not attained). Modeling the longitudinal data on all girls showed that sexual debut was associated with increased odds of vaginal and anorectal G vaginalis (P=.021; P=.030) and A vaginae (P=.041; P=.012) with increments of interleukins (interleukin [IL]-1alpha P<.001, IL-1beta P=.046, IL-8 P=.033) and chemokines (regulated on activation, normal T cell expressed and secreted P<.001; macrophage inflammatory protein-1beta P=.040), whereas no difference was seen when modeling (before-after) the girls initiating and girls staying without sexual intercourse. The association of sexual intercourse with IL 1alpha (P<.001), IL-1beta (P=.030), and IL-8 (P=.002) at the first visit was (greater than 70%) mediated by vaginal G vaginalis and A vaginae concentrations. CONCLUSION: Sexual debut in adolescents is associated with an inflammatory vaginal reaction and with the presence of bacterial vaginosis-related species. Strategies preventing the colonization of bacterial vaginosis-related organisms during early sexual debut are urgently needed and may prevent acquisition of sexually transmitted infections including human immunodeficiency virus in early life. PMID- 27275790 TI - Rhabdomyolysis After Hyperemesis Gravidarum. AB - BACKGROUND: Hyperemesis gravidarum may lead to hypovolemia and substantial electrolyte abnormalities, including hypokalemia. Hypokalemia, when profound, may result in rare consequences, such as rhabdomyolysis. CASE: A 20-year-old woman with hyperemesis gravidarum at 19 weeks of gestation presented with extreme leg weakness and was found to have hypokalemia and hypophosphatemia. Her course was complicated by rhabdomyolysis, which, after excluding other causes, was attributed to hypokalemia and severe dehydration. After aggressive electrolyte and hydration repletion, she experienced resolution of her symptoms. CONCLUSION: Pregnancies complicated by hyperemesis gravidarum represent potentially high-risk clinical scenarios for electrolyte abnormalities and subsequent complications, including rhabdomyolysis. PMID- 27275791 TI - High-Dose Methylprednisolone to Prevent Platelet Decline in Preeclampsia: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate whether early administration of high-dose methylprednisolone limits the fall of platelets in preeclampsia. METHODS: A randomized trial of 180 mg methylprednisolone or placebo administered in divided doses over 36 hours was conducted in women admitted for preeclampsia and platelet counts below 150*10/L in four French academic centers. Patients were not included when platelet counts were below 50*10/L or when immediate delivery was required. The primary study outcome was the proportion of patients with platelet counts above 100*10/L 36 hours after the first dose of study medication. The total sample size needed to detect a 23% difference in the rate of this outcome between groups with a one-tailed alpha of 0.05 and 90% power was 94 patients. RESULTS: Thirty-six patients were randomly assigned to receive methylprednisolone and 34 placebo between October 2007 and May 2011. Platelet counts above 100*10/L at 36 hours after the first dose of study medication were recorded in 30 (83%) in the active group and 29 (85%) in the placebo group (relative risk 0.98, 95% confidence interval 0.80-1.20; P=.82). The only adverse potentially study-related event was hyperglycemia in one woman allocated to methylprednisolone. CONCLUSION: In women with preeclampsia and platelet counts under 150*10/L, methylprednisolone was not effective in maintaining platelet counts above 100*10/L. CLINICAL TRIAL REGISTRATION: EU Clinical Trials Register, http://clinicaltrialsregister.eu, EudraCT 2006-004881-15-FR. PMID- 27275792 TI - Pregnancy-Associated Deaths in Rural, Nonrural, and Metropolitan Areas of Georgia. AB - OBJECTIVE: To characterize pregnancy-associated deaths and examine the relationship between area of residence and pregnancy-associated deaths and pregnancy-related mortality ratios in Georgia from 2010 to 2012. METHODS: The cohort of pregnancy-associated deaths was reviewed and categorized as pregnancy related or resulting from other medical conditions not related to pregnancy, suicide, drug toxicity, homicide, or motor vehicle accident. Georgia Online Analytical Statistical Information System data were used to calculate pregnancy related mortality ratio by rural, nonrural, and metropolitan Atlanta area and by race. Causes of death and pregnancy-related mortality ratio were compared by area of residence and race using chi tests; a P value <.05 was considered significant. RESULTS: There were 262 pregnancy-associated deaths; 40.1% (n=105) were pregnancy related. The 2010-2012 pregnancy-related mortality ratio was 26.5 per 100,000 live births and the pregnancy-related mortality ratio did not differ statistically among rural (27.1), nonrural (24.4), and metropolitan Atlanta (27.7) areas (P=.845). Most pregnancy-related deaths were the result of hemorrhage and cardiovascular factors. In aggregate, the pregnancy-related mortality ratio for black women was 49.5 compared with 14.3 for white women (P<.001). The gap in pregnancy-related mortality ratio between black and white women was highest for metropolitan Atlanta (51.6 compared with 12.4, P<.001), less in nonrural areas (50.3 compared with 12.0, P<.001), and comparable in rural areas (39.4 compared with 22.4, P=.281). CONCLUSION: Although the pregnancy related mortality ratio was similar for rural, nonrural, and metropolitan Atlanta areas, it was significantly higher for black compared with white women living outside of rural areas. PMID- 27275793 TI - Integrating Preexposure Prophylaxis for Human Immunodeficiency Virus Prevention Into Women's Health Care in the United States. AB - Women comprise one in five new human immunodeficiency virus (HIV) diagnoses in the United States. Trials and implementation projects demonstrate preexposure prophylaxis for HIV prevention is effective in women. Preexposure prophylaxis is a method of preventing HIV acquisition by having an HIV-negative individual take antiretroviral medication before exposure. The U.S. Food and Drug Administration approved daily oral tenofovir disoproxil fumarate coformulated with emtricitabine as preexposure prophylaxis for HIV prevention in 2012. Preexposure prophylaxis is highly dependent on adherence for effectiveness. The Centers for Disease Control and Prevention recommends offering preexposure prophylaxis to individuals at significant risk of infection and estimates 468,000 women in the United States are eligible for preexposure prophylaxis. Although variable individual and structural forces affect each woman's medication adherence, and therefore the effectiveness of preexposure prophylaxis, women's health care providers are uniquely positioned to screen, counsel about, and offer preexposure prophylaxis. Shared decision-making provides a framework for these clinical encounters, allowing patients and clinicians to make health care decisions together based on scientific evidence and patient experiences. By incorporating fertility desires and contraceptive needs, health care providers effectively integrate sexual and reproductive health care. Including preexposure prophylaxis in women's health services requires health care provider training and attention to lessons learned from family planning and HIV prevention. Nevertheless, obstetrician-gynecologists have an opportunity to play a critical role in reducing sexual transmission of HIV in the United States by integrating preexposure prophylaxis education and provision into their practices. PMID- 27275794 TI - Baseline Renal Function Tests and Adverse Outcomes in Pregnant Patients With Chronic Hypertension. AB - OBJECTIVE: To examine the relationship between baseline renal function tests in pregnant patients with chronic hypertension and adverse pregnancy outcomes. METHODS: This was a retrospective cohort study of women with a singleton pregnancy and chronic hypertension with assessment of renal function (urine protein-to-creatinine ratio and serum creatinine) before 20 weeks of gestation. The primary outcome was severe preeclampsia at less than 34 weeks of gestation. Secondary outcomes were severe preeclampsia at any gestational age, any preeclampsia, preterm birth at less than 35 weeks of gestation, composite perinatal outcome (perinatal death, assisted ventilation, cord pH less than 7, 5 minute Apgar score 3 or less, or neonatal seizures), and small for gestational age. The association between baseline renal function and the primary outcome was assessed with receiver operating characteristic (ROC) curves and objective cutoffs determined. Outcomes were compared between those with values above and below the cutoffs using univariable and multivariable analyses. RESULTS: Seven hundred fifty-five pregnant women with chronic hypertension had baseline renal function assessment. The urine protein-to-creatinine ratio and creatinine cutoffs for severe preeclampsia at less than 34 weeks of gestation were 0.12 or greater and 0.75 mg/dL or greater, respectively. The area under the ROC curves for severe preeclampsia at less than 34 weeks of gestation was 0.74 (95% confidence interval [CI] 0.7-0.8) for urine protein-to-creatinine ratio and 0.67 (95% CI 0.6-0.8) for creatinine. A urine protein-to-creatinine ratio 0.12 or greater was associated with an increased risk of developing severe preeclampsia at less than 34 weeks of gestation (16.4% compared with 2.6%, adjusted odds ratio [OR] 7.5, 95% CI 3.9 14.6) as was a creatinine 0.75 mg/dL or greater (15.7% compared with 4.6%, adjusted OR 3.5, 95% CI 1.9-6.3). Severe preeclampsia at less than 34 weeks of gestation occurred in only 1.6% of patients if their baseline tests were below both cutoffs. CONCLUSION: Baseline assessment of renal function can be used as a risk stratification tool in pregnant patients with chronic hypertension. PMID- 27275795 TI - Control of Postpartum Hemorrhage Using Vacuum-Induced Uterine Tamponade. AB - BACKGROUND: Postpartum hemorrhage is the leading cause of maternal mortality worldwide. Vacuum-induced uterine tamponade is a possible alternative approach to balloon tamponade systems for the treatment of postpartum hemorrhage resulting from atony. METHOD: In a prospective proof-of-concept investigation of 10 women with vaginal deliveries in a hospital setting who failed first-line therapies for postpartum hemorrhage, tamponade was used. Vacuum-induced uterine tamponade was created through a device inserted transvaginally into the uterine cavity. An occlusion balloon built into the device shaft was inflated at the level of the external cervical os to create a uterine seal. Negative pressure was created by attaching a self-contained, mobile, electrically powered, pressure-regulated vacuum pump with a sterile graduated canister. EXPERIENCE: In all 10 cases, the suction created an immediate seal at the cervical os, 50-250 mL of residual blood was evacuated from the uterine cavity, the uterus collapsed and regained tone within minutes, and hemorrhaging was controlled. The device remained in place for a minimum of 1 hour and up to 6.5 hours in one case while vaginal and perineal lacerations were easily repaired. CONCLUSION: This preliminary investigation suggests that a device designed to create vacuum-induced uterine tamponade may be a reasonable alternative to other devices used to treat atonic postpartum hemorrhage. PMID- 27275796 TI - Postpartum Human Immunodeficiency Virus Care Among Women Diagnosed During Pregnancy. AB - OBJECTIVE: To identify factors associated with continuity of care and human immunodeficiency virus (HIV) virologic suppression among postpartum women diagnosed with HIV during pregnancy in New York State. METHODS: This retrospective cohort study was conducted among 228 HIV-infected women diagnosed during pregnancy between 2008 and 2010. Initial receipt of HIV-related medical care (first CD4 or viral load test after diagnosis) was evaluated at 30 days after diagnosis and before delivery. Retention in care (2 or more CD4 or viral load tests, 90 days or greater apart) and virologic suppression (viral load 200 copies/mL or less) were evaluated in the 12 months after hospital discharge. RESULTS: Most women had their initial HIV-related care encounter within 30 days of diagnosis (74%) and before delivery (87%). Of these women, 70% were retained in the first year postpartum. Women waiting more than 30 days for their initial HIV-related care encounter were more likely diagnosed in the first (29%) compared with the third (11%) trimester and were of younger (younger than 25 years, 32%) compared with older (35 years or older, 13%) age. Loss to follow-up within the first year was significantly greater among women diagnosed in the third compared with the first trimester (adjusted relative risk 2.21, 95% confidence interval [CI] 1.41-3.45) and among women who had a cesarean compared with vaginal delivery (adjusted relative risk 1.76, 95% CI 1.07-2.91). Of the 178 women with one or more HIV viral load test in the first year postpartum, 58% had an unsuppressed viral load. CONCLUSION: Despite the high proportion retained in care, many women had poor postpartum virologic control. Robust strategies are needed to increase virologic suppression among newly diagnosed postpartum HIV-infected women. PMID- 27275797 TI - Enhanced Recovery Pathways for Improving Outcomes After Minimally Invasive Gynecologic Oncology Surgery. AB - OBJECTIVE: To estimate whether an enhanced recovery after surgery pathway facilitates early recovery and discharge in gynecologic oncology patients undergoing minimally invasive surgery. METHODS: This was a retrospective case control study. Consecutive gynecologic oncology patients undergoing laparoscopic or robotic surgery between July 1 and November 5, 2014, were treated on an enhanced recovery pathway. Enhanced recovery pathway components included patient education, multimodal analgesia, opioid minimization, nausea prophylaxis as well as early catheter removal, ambulation, and feeding. Cases were matched in a one to-two ratio with historical control patients on the basis of surgery type and age. Primary endpoints were length of hospital stay, rates of discharge by noon, 30-day hospital readmission rates, and hospital costs. RESULTS: There were 165 patients included in the final cohort, 55 of whom were enhanced recovery pathway patients. Enhanced recovery patients were more likely to be discharged on postoperative day 1 compared with patients in the control group (91% compared with 60%, P<.001, odds ratio 6.7, 95% confidence interval 2.46-18.04). Fifteen percent of enhanced recovery patients achieved discharge by noon compared with 4% of historical control patients (P=.03). Postoperative pain scores decreased (2.6 compared with 3.12, P=.03) despite a 30% reduction in opioid use. Average total hospital costs were decreased by 12% in the enhanced recovery group ($13,771 compared with $15,649, P=.01). Readmission rates, mortality, and reoperation rates did not differ between the two groups. CONCLUSION: An enhanced recovery pathway in patients undergoing gynecologic oncology minimally invasive surgery is associated with significant improvements in recovery time, decreased pain despite reduced opioid use, and overall lower hospital costs. PMID- 27275798 TI - Vaginal Pessary in Women With Symptomatic Pelvic Organ Prolapse: A Randomized Controlled Trial. AB - OBJECTIVE: To compare pelvic floor symptoms, quality of life, and complications in women with symptomatic pelvic organ prolapse (POP) with or without vaginal pessaries in addition to those who do pelvic floor exercises for 12 months. METHODS: This was a parallel-group, single-blind, randomized controlled trial with 12 months of follow-up. Women with symptomatic stage I to stage III POP were randomized to either pelvic floor exercises training (control group) or pelvic floor exercises training and insertion of a vaginal pessary (pessary group). The primary outcome was the change of prolapse symptoms and quality of life by using the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaires. Secondary outcomes included bothersome of prolapse symptoms, desired treatment, and any complications. RESULTS: From December 2011 through November 2014, 311 women were screened and 276 were randomized as follows: 137 to the control and 139 to the pessary group. One hundred thirty-two (95.0%) women in the pessary group and 128 (93.4%) in the control group completed the study. The Pelvic Organ Prolapse Distress Inventory of Pelvic Floor Distress Inventory and the Pelvic Organ Prolapse Impact Questionnaire of Pelvic Floor Impact Questionnaire scores decreased in both groups after 12 months, but the mean score differences were higher in the pessary group (Pelvic Organ Prolapse Distress Inventory: -29.7 compared with -4.7, P<.01; Pelvic Organ Prolapse Impact Questionnaire: -29.0 compared with 3.5, P<.01). Complication rates were low and similar in both groups. CONCLUSION: We provided further evidence in nonsurgical treatment for POP. Prolapse symptoms and quality of life were improved in women using a vaginal pessary in addition to pelvic floor exercises. CLINICAL TRIAL REGISTRATION: Centre for Clinical Research and Biostatistics-Clinical Trials Registry, https://www2.ccrb.cuhk.edu.hk/web/?page_id=746, ChiCTR-TRC-11001796. PMID- 27275799 TI - Pregnancy Intentions and Safer Pregnancy Knowledge Among Female Sex Workers in Port Elizabeth, South Africa. AB - OBJECTIVE: To assess the association between human immunodeficiency virus (HIV) and pregnancy intentions and safer conception knowledge among female sex workers in Port Elizabeth, South Africa. METHODS: This cross-sectional study recruited female sex workers in Port Elizabeth using respondent-driven sampling and completed an interviewer-administered questionnaire alongside HIV testing and counseling. In this secondary analysis, robust Poisson regression was used to model prevalence ratios for positive fertility intentions in this cross-sectional study. Knowledge of safer conception methods by HIV status was compared using Fisher exact tests. RESULTS: Overall 391 women were represented in the analyses. More than 50% had a prior HIV diagnosis, and an additional 12% were diagnosed with HIV during the study. Approximately half (n=185) of the women reported future pregnancy intentions. In univariate analysis, a prior HIV diagnosis was negatively associated with pregnancy intentions as compared with HIV-negative women (prevalence ratio 0.68, 95% confidence interval 0.55-0.85). Only parity remained independently associated with future pregnancy intentions in multivariate regression after controlling for HIV status, age, race, relationship status, and years selling sex. Knowledge of safer conception methods such as timed sex without a condom, preexposure prophylaxis, or self-insemination was low and similar between those with and without future pregnancy plans. CONCLUSION: Pregnancy intentions did not significantly vary according to HIV status. Fertility intentions were high, however, and knowledge of safer conception methods low, suggesting a need to provide female sex workers with advice around options to conceive safely in the context of high HIV prevalence. PMID- 27275800 TI - Obstetric and Neonatal Risks Among Obese Women Without Chronic Disease. AB - OBJECTIVE: To investigate whether prepregnancy obesity is associated with adverse pregnancy outcomes among women without chronic disease. METHODS: Singleton deliveries (N=112,309) among mothers without chronic diseases in the Consortium on Safe Labor, a retrospective U.S. cohort, were analyzed using Poisson regression with robust variance estimation. Relative risks and 95% confidence intervals (CIs) estimated perinatal risks in relation to prepregnancy obesity status adjusted for age, race-ethnicity, parity, insurance, smoking and alcohol use during pregnancy, and study site. RESULTS: Obstetric risks were variably (and mostly marginally) increased as body mass index (BMI) category and obesity class increased. In particular, the risk of gestational hypertensive disorders, gestational diabetes, cesarean delivery, and induction increased in a dose response fashion. For example, the percentage of gestational diabetes among obese class III women was 14.6% in contrast to 2.8% among women with normal BMIs (corresponding relative risks [95% CI] 1.99 [1.86-2.13], 2.94 [2.73-3.18], 3.97 [3.61-4.36], and 5.47 [4.96-6.04] for overweight, obese class I, obese class II, and obese class III women, respectively) compared with women with normal BMIs. Similarly, neonatal risks increased in a dose-response fashion with maternal BMI status including preterm birth at less than 32 weeks of gestation, large for gestational age (LGA), transient tachypnea, sepsis, and intensive care unit admission. The percentage of LGA neonates increased from 7.9% among women with normal BMIs to 17.3% among obese class III women and relative risks increased to 1.52 (1.45-1.58), 1.74 (1.65-1.83), 1.93 (1.79-2.07), and 2.32 (2.14-2.52) as BMI category increased. CONCLUSION: Prepregnancy obesity is associated with increased risks of a wide range of adverse pregnancy and neonatal outcomes among women without chronic diseases. PMID- 27275801 TI - Acute Babesiosis in Pregnancy: A Novel Imitator of Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome. AB - BACKGROUND: Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a serious complication of pregnancy associated with significant maternal and fetal morbidity and mortality. Several medical conditions have been described as imitators of this syndrome, presenting with similar signs and symptoms. CASE: A term, multiparous woman with a history of prior pregnancy complicated by preeclampsia developed symptoms and laboratory abnormalities suggestive of HELLP syndrome. After an uncomplicated repeat caesarean delivery of a healthy newborn, infection with Babesia species was diagnosed incidentally on a peripheral blood smear. She was treated with antibiotics postpartum without sequelae for her or her newborn. The laboratory abnormalities normalized by postoperative day 4. CONCLUSION: Babesiosis complicating pregnancy may be a novel imitator of HELLP syndrome and should be considered in the differential diagnosis, especially where geographically prevalent infection exists. PMID- 27275802 TI - Association of Low-Dose Aspirin and Survival of Women With Endometrial Cancer. AB - OBJECTIVE: To examine the survival outcomes in women with endometrial cancer who were taking low-dose aspirin (81-100 mg/d). METHODS: A multicenter retrospective study was conducted examining patients with stage I-IV endometrial cancer who underwent hysterectomy-based surgical staging between January 2000 and December 2013 (N=1,687). Patient demographics, medical comorbidities, medication types, tumor characteristics, and treatment patterns were correlated to survival outcomes. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio for disease-free and disease-specific overall survival. RESULTS: One hundred fifty-eight patients (9.4%, 95% confidence interval [CI] 8.8 11.9) were taking low-dose aspirin. Median follow-up time for the study cohort was 31.5 months. One hundred twenty-seven patients (7.5%) died of endometrial cancer. Low-dose aspirin use was significantly correlated with concurrent obesity, hypertension, diabetes mellitus, and hypercholesterolemia (all P<.001). Low-dose aspirin users were more likely to take other antihypertensive, antiglycemic, and anticholesterol agents (all P<.05). Low-dose aspirin use was not associated with histologic subtype, tumor grade, nodal metastasis, or cancer stage (all P>.05). On multivariable analysis, low-dose aspirin use remained an independent prognostic factor associated with an improved 5-year disease-free survival rate (90.6% compared with 80.9%, adjusted hazard ratio 0.46, 95% CI 0.25 0.86, P=.014) and disease-specific overall survival rate (96.4% compared with 87.3%, adjusted hazard ratio 0.23, 95% CI 0.08-0.64, P=.005). The increased survival effect noted with low-dose aspirin use was greatest in patients whose age was younger than 60 years (5-year disease-free survival rates, 93.9% compared with 84.0%, P=.013), body mass index was 30 or greater (92.2% compared with 81.4%, P=.027), who had type I cancer (96.5% compared with 88.6%, P=.029), and who received postoperative whole pelvic radiotherapy (88.2% compared with 61.5%, P=.014). These four factors remained significant for disease-specific overall survival (all P<.05). CONCLUSION: Our results suggest that low-dose aspirin use is associated with improved survival outcomes in women with endometrial cancer, especially in those who are young, obese, with low-grade disease, and who receive postoperative radiotherapy. PMID- 27275803 TI - Surgeon Experience and Complications of Transvaginal Prolapse Mesh. AB - OBJECTIVE: To measure the proportion of women with transvaginal prolapse mesh complications and their association with surgeon volume. METHODS: We conducted a retrospective, population-based cohort study of all women who underwent a mesh based prolapse procedure using administrative data (hospital procedure and physician billing records) between 2002 and 2013 in Ontario, Canada. The primary outcome was surgical revision of the mesh. Primary exposure was surgeon volume: high (greater than the 75th percentile, requiring a median of five [interquartile range 5-6] procedures per year) and very high (greater than the 90th percentile, requiring a median of 13 [interquartile range 11-14] procedures per year) volume mesh implanters were identified each year. Primary analysis was an adjusted Cox proportional hazards model. RESULTS: A total of 5,488 women underwent mesh implantation by 1 of 368 unique surgeons. Median follow-up time was 5.4 (interquartile range 3.0-8.0) years. We found that 218 women (4.0%) underwent mesh reoperation a median of 1.17 (interquartile range 0.58-2.90) years after implantation. The hazard of reoperation for complications was only lower for patients of very high-volume surgeons (3.0% [145/3,001] compared with 4.8% [73/2,447], adjusted hazards ratio 0.59, 95% confidence interval 0.40-0.86). In multivariable modeling, younger age, concomitant hysterectomy, blood transfusion, and increased medical comorbidity were all associated with vaginal mesh reoperation. CONCLUSION: Approximately 5% of women who underwent mesh-based prolapse surgery required reoperation for a mesh complication within 10 years. The risk of reoperation was lowest for surgeons performing 14 or more procedures per year. PMID- 27275804 TI - Ensuring Access to Safe, Legal Abortion in an Increasingly Complex Regulatory Environment. AB - Restrictions on access to abortion in the United States have reached proportions unprecedented since the nationwide legalization of abortion in 1973. Although some restrictions aim to discourage women from having abortions, many others impede access by affecting the timeliness, affordability, or availability of services. Evidence indicates that these restrictions do not increase abortion safety; rather, they create logistic barriers for women seeking abortion, and they have the greatest effect on women with the fewest resources. In this commentary, we recall the important role that obstetrician-gynecologists (ob gyns) have played, both before and after Roe v. Wade, in facilitating access to safe abortion care. Using the literature on abortion safety and access as a foundation, we propose several practical ideas about what we as ob-gyns can do to address the current threat to abortion access, whether or not we provide abortion services in practice. We hope that this commentary will encourage discourse within our profession and prompt other suggestions. As ob-gyns who are dedicated to addressing health disparities and promoting the health and well-being of our patients, we can make a difference. PMID- 27275805 TI - Venous Thromboembolism in Minimally Invasive Compared With Open Hysterectomy for Endometrial Cancer. AB - OBJECTIVE: To evaluate whether minimally invasive surgery for endometrial cancer is independently associated with a decreased odds of venous thromboembolism compared with open surgery. METHODS: We performed a secondary analysis cohort study of prospectively collected quality improvement data and examined patients undergoing hysterectomy for endometrial cancer from 2008 to 2013 recorded in the National Surgical Quality Improvement Program database. Patients undergoing minimally invasive (laparoscopic or robotic) surgery were compared with those undergoing open surgery with respect to 30-day postoperative venous thromboembolism. Demographic and procedure variables were examined as potential confounders. Data regarding receipt of perioperative venous thromboembolism prophylaxis were not available. Bivariable tests and logistic regression were used for analysis. RESULTS: Of 9,948 patients who underwent hysterectomy for the treatment of endometrial cancer, 61.9% underwent minimally invasive surgery and 38.1% underwent open surgery. Patients undergoing minimally invasive surgery had a lower venous thromboembolism incidence (0.7%, n=47) than patients undergoing open surgery (2.2%, n=80) (P<.001). In a multivariate model adjusting for age, body mass index, race, operative time, Charlson comorbidity score, and surgical complexity, minimally invasive surgery remained associated with decreased odds of venous thromboembolism (adjusted odds ratio 0.36, 95% confidence interval 0.24 0.53) compared with open surgery. CONCLUSION: Minimally invasive surgery for the treatment of endometrial cancer is independently associated with decreased odds of venous thromboembolism compared with open surgery. PMID- 27275806 TI - Reduction in the Cesarean Delivery Rate After Obstetric Care Consensus Guideline Implementation. AB - OBJECTIVE: To evaluate the rate of primary cesarean delivery after adopting labor management guidelines. METHODS: This is a before-after retrospective cohort study at a single academic center. This center adopted guidelines from the Consensus for the Prevention of the Primary Cesarean Delivery. Nulliparous women attempting vaginal delivery with viable, singleton, vertex fetuses were included. For the primary outcome of cesarean delivery rate among induced or augmented patients, 200 consecutive women managed before guideline adoption were compared with 200 similar patients afterward. Secondary outcomes of overall cesarean delivery rate, maternal morbidity, neonatal outcomes, and labor management practices were analyzed with inclusion of intervening spontaneously laboring women. RESULTS: Between September 13, 2013, and September 28, 2014, 275 women preguideline and 292 postguideline were identified to include 200 deliveries after induction or augmentation each. Among women delivering after induction or augmentation, the cesarean delivery rate decreased from 35.5% to 24.5% (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.38-0.91). The overall cesarean delivery rate decreased from 26.9% to 18.8% (adjusted OR 0.59, CI 0.38-0.92). Composite maternal morbidity was reduced (adjusted OR 0.66, CI 0.46-0.94). The frequency of cesarean delivery documenting arrest of dilation at less than 6 cm decreased from 7.1% to 1.1% postguideline (n=182 and 176 preguideline and postguideline, respectively, P=.006) with no change in other indications. CONCLUSION: Postguideline, the cesarean delivery rate among nulliparous women attempting vaginal delivery was substantially reduced in association with decreased frequency in the diagnosis of arrest of dilation at less than 6 cm. PMID- 27275807 TI - Making Room at the Table for Obstetrics, Midwifery, and a Culture of Normalcy Within Maternity Care. AB - The principle of avoiding the worst possible outcomes guided the enormous successes of modern obstetrics in reducing the morbidity and mortality of childbirth. The challenges of improving the quality of childbirth today has prompted health care providers, policymakers, and patients to ask whether this principle is in fact preventing us from supporting the normal processes of childbirth, resulting in undue intervention and potentially causing harm. In this commentary, we suggest that recognizing the strengths of the medical model of childbirth does not preclude looking outside of it to meet the maternity care needs of the majority of healthy, low-risk women. Obstetricians have the good fortune to have a partner in their work among midwives, who hail from a long tradition of incorporating a perspective of "normalcy" in the care of childbearing women. Given the many evidence-based practices demonstrating the strengths of midwifery to actualize patient-centered, low-intervention birth, we advocate for the explicit establishment of professional standards for team-based physician-midwife care. More than merely introducing midwives into a physician dominated setting, this means elevating the contributions of midwives and meaningfully incorporating a culture of normalcy to standardize practices such as intermittent auscultation, continuous birth support, nonpharmacologic pain management, and positional flexibility in labor. The literature suggests that a woman's health care provider is the most powerful determinant of her birth outcomes; striking the balance between averting poor outcomes and normalcy compels us to make room at the table for both obstetricians and midwives. PMID- 27275808 TI - Prescription of Hormonal Contraception by Pharmacists in Oregon: Implementation of House Bill 2879. AB - Prescription of hormonal contraception by pharmacists, without a doctor's visit or authorization, has been proposed as a strategy to improve access to contraception and reduce unintended pregnancy. Oregon is the first state to implement legislation expanding the scope of pharmacists to directly prescribe and dispense short-acting hormonal contraception (pill and patch). Several other states are considering similar legislation. Implementation of the policy is being researched to identify both barriers and facilitators to the successful dissemination of the practice and to determine the safety, efficacy, and acceptability of pharmacist-prescribed contraception. PMID- 27275809 TI - What Is New in Medical Student and Resident Education?: Best Articles From the Past Year. AB - This month we focus on current research in medical student and resident education. Dr. Fox discusses four recent publications, which are concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in Box 1 on this page, along with direct links to the abstracts. PMID- 27275810 TI - Screening, Prevention, and Treatment of Opioid Use Disorder During Pregnancy: Expectant Mothers Are Depending on You! PMID- 27275811 TI - The Next Generation of Health Care. PMID- 27275812 TI - Opioid Use Disorder in Pregnancy: Health Policy and Practice in the Midst of an Epidemic. AB - Opioid abuse among pregnant women has reached epidemic proportions and has influenced maternal and child health policy at the federal, state, and local levels. As a result, we review the current state of opioid use in pregnancy and evaluate recent legislative and health policy initiatives designed to combat opioid addiction in pregnancy. We emphasize the importance of safe and responsible opioid-prescribing practices, expanding the availability and accessibility of medication-assisted treatment and standardizing care for neonates at risk of neonatal abstinence syndrome. Efforts to penalize pregnant women and negative consequences for disclosing substance use to health care providers are harmful and may prevent women from seeking prenatal care and other beneficial health care services during pregnancy. Instead, health care providers should advocate for health policy informed by scientific research and evidence based practice to reduce the burden of prenatal opioid abuse and optimize outcomes for mothers and their neonates. PMID- 27275814 TI - Connect the Dots-July 2016. PMID- 27275813 TI - Graft and Mesh Use in Transvaginal Prolapse Repair: A Systematic Review. AB - OBJECTIVE: To update clinical practice guidelines on graft and mesh use in transvaginal pelvic organ prolapse repair based on systematic review. DATA SOURCES: Eligible studies, published through April 2015, were retrieved through ClinicalTrials.gov, MEDLINE, and Cochrane databases and bibliography searches. METHODS OF STUDY SELECTION: We included studies of transvaginal prolapse repair that compared graft or mesh use with either native tissue repair or use of a different graft or mesh with anatomic and symptomatic outcomes with a minimum of 12 months of follow-up. TABULATION, INTEGRATION, AND RESULTS: Study data were extracted by one reviewer and confirmed by a second reviewer. Studies were classified by vaginal compartment (anterior, posterior, apical, or multiple), graft type (biologic, synthetic absorbable, synthetic nonabsorbable), and outcome (anatomic, symptomatic, sexual function, mesh complications, and return to the operating room). We found 66 comparative studies reported in 70 articles, including 38 randomized trials; quality of the literature has improved over time, but some outcomes still show heterogeneity and limited power. In the anterior vaginal compartment, synthetic nonabsorbable mesh consistently showed improved anatomic and bulge symptom outcomes compared with native tissue repairs based on meta-analyses. Other subjective outcomes, including urinary incontinence or dyspareunia, generally did not differ. Biologic graft or synthetic absorbable mesh use did not provide an advantage in any compartment. Synthetic mesh use in the posterior or apical compartments did not improve success. Mesh erosion rates ranged from 1.4-19% at the anterior vaginal wall, but 3-36% when mesh was placed in multiple compartments. Operative mesh revision rates ranged from 3-8%. CONCLUSION: Synthetic mesh augmentation of anterior wall prolapse repair improves anatomic outcomes and bulge symptoms compared with native tissue repair. Biologic grafts do not improve prolapse repair outcomes in any compartment. Mesh erosion occurred in up to 36% of patients, but reoperation rates were low. PMID- 27275815 TI - Abnormal Vaginal Pap Test Results After Hysterectomy in Human Immunodeficiency Virus-Infected Women. AB - OBJECTIVE: To evaluate the prevalence of abnormal vaginal cytology and vaginal intraepithelial neoplasia (VAIN) and vaginal cancer in human immunodeficiency virus (HIV)-infected women with no history of abnormal cytologic screening who had a hysterectomy for conditions other than cervical dysplasia and cancer and to explore the risk factors associated with VAIN and vaginal cancer. METHODS: A retrospective cohort study was performed identifying 238 women between January 2000 and January 2015 with a history of HIV, previous hysterectomy, and no previous abnormal Pap test results. Medical records from patients with both HIV and a history of hysterectomy were reviewed from Thomas Street Health Center and Northwest Community Health Center. RESULTS: Among 238 women, 164 (69%) had normal Pap test results, 12 (5%) had results showing atypical cells of undermined significance and human papillomavirus-positive, 55 (23.1%) had results showing low-grade squamous intraepithelial lesion, and seven (2.9%) had results showing high-grade squamous intraepithelial lesion. No demographic risk factor was associated with abnormal Pap test results after hysterectomy. Median follow-up time for the Pap test was 16 years. Of those who underwent vaginal biopsies for abnormal Pap test results, 15 (28%) had normal results, 23 (43%) had VAIN 1, nine (16%) had VAIN 2, and seven (13%) had VAIN 3. No patients had invasive vaginal cancer. CONCLUSION: More than 30% of HIV-infected women who had no prehysterectomy history of abnormal Pap test results had abnormal vaginal Pap test results. Among those who had vaginal biopsies, 29% had VAIN 2 or 3, suggesting that Pap testing posthysterectomy in the HIV population may be indicated. PMID- 27275817 TI - The Complete Chloroplast Genome Sequences of the Medicinal Plant Pogostemon cablin. AB - Pogostemon cablin, the natural source of patchouli alcohol, is an important herb in the Lamiaceae family. Here, we present the entire chloroplast genome of P. cablin. This genome, with 38.24% GC content, is 152,460 bp in length. The genome presents a typical quadripartite structure with two inverted repeats (each 25,417 bp in length), separated by one small and one large single-copy region (17,652 and 83,974 bp in length, respectively). The chloroplast genome encodes 127 genes, of which 107 genes are single-copy, including 79 protein-coding genes, four rRNA genes, and 24 tRNA genes. The genome structure, GC content, and codon usage of this chloroplast genome are similar to those of other species in the family, except that it encodes less protein-coding genes and tRNA genes. Phylogenetic analysis reveals that P. cablin diverged from the Scutellarioideae clade about 29.45 million years ago (Mya). Furthermore, most of the simple sequence repeats (SSRs) are short polyadenine or polythymine repeats that contribute to high AT content in the chloroplast genome. Complete sequences and annotation of P. cablin chloroplast genome will facilitate phylogenic, population and genetic engineering research investigations involving this particular species. PMID- 27275816 TI - Human Saliva Collection Devices for Proteomics: An Update. AB - There has been a rapid growth in the interest and adaptation of saliva as a diagnostic specimen over the last decade, and in the last few years in particular, there have been major developments involving the application of saliva as a clinically relevant specimen. Saliva provides a "window" into the oral and systemic health of an individual, and like other bodily fluids, saliva can be analyzed and studied to diagnose diseases. With the advent of new, more sensitive technologies to detect smaller concentrations of analytes in saliva relative to blood levels, there have been a number of critical developments in the field that we will describe. In particular, recent advances in standardized saliva collection devices that were not available three to four years ago, have made it easy for safe, simple, and non-invasive collection of samples to be carried out from patients. With the availability of these new technologies, we believe that in the next decade salivary proteomics will make it possible to predict and diagnose oral as well as systemic diseases, cancer, and infectious diseases, among others. The aim of this article is to review recent developments and advances in the area of saliva specimen collection devices and applications that will advance the field of proteomics. PMID- 27275818 TI - Gene Set-Based Functionome Analysis of Pathogenesis in Epithelial Ovarian Serous Carcinoma and the Molecular Features in Different FIGO Stages. AB - Serous carcinoma (SC) is the most common subtype of epithelial ovarian carcinoma and is divided into four stages by the Federation of Gynecologists and Obstetrics (FIGO) staging system. Currently, the molecular functions and biological processes of SC at different FIGO stages have not been quantified. Here, we conducted a whole-genome integrative analysis to investigate the functions of SC at different stages. The function, as defined by the GO term or canonical pathway gene set, was quantified by measuring the changes in the gene expressional order between cancerous and normal control states. The quantified function, i.e., the gene set regularity (GSR) index, was utilized to investigate the pathogenesis and functional regulation of SC at different FIGO stages. We showed that the informativeness of the GSR indices was sufficient for accurate pattern recognition and classification for machine learning. The function regularity presented by the GSR indices showed stepwise deterioration during SC progression from FIGO stage I to stage IV. The pathogenesis of SC was centered on cell cycle deregulation and accompanied with multiple functional aberrations as well as their interactions. PMID- 27275819 TI - Could Vitamin D Analogues Be Used to Target Leukemia Stem Cells? AB - Leukemic stem cells (LSCs) are defined as cells that possess the ability to self renew and give rise to the differentiated cancer cells that comprise the tumor. These LSCs seem to show chemo-resistance and radio-resistance leading to the failure of conventional cancer therapies. Current therapies are directed at the fast growing tumor mass leaving the LSC fraction untouched. Eliminating LSCs, the root of cancer origin and recurrence, is considered to be a hopeful approach to improve survival or even to cure cancer patients. In order to achieve this, the characterization of LSCs is a prerequisite in order to develop LSC-based therapies to eliminate them. Here we review if vitamin D analogues may allow an avenue to target the LSCs. PMID- 27275822 TI - Fire Source Localization Based on Distributed Temperature Sensing by a Dual-Line Optical Fiber System. AB - We propose a method for localizing a fire source using an optical fiber distributed temperature sensor system. A section of two parallel optical fibers employed as the sensing element is installed near the ceiling of a closed room in which the fire source is located. By measuring the temperature of hot air flows, the problem of three-dimensional fire source localization is transformed to two dimensions. The method of the source location is verified with experiments using burning alcohol as fire source, and it is demonstrated that the method represents a robust and reliable technique for localizing a fire source also for long sensing ranges. PMID- 27275820 TI - Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability. AB - Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies. PMID- 27275821 TI - Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir. AB - The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV) system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium (BF) and HSV TK/GCV (BF-rTK/GCV). However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV) was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However, the BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular endothelial growth factor (VEGF) expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way for cancer gene therapy. PMID- 27275823 TI - A MEMS Resonant Sensor to Measure Fluid Density and Viscosity under Flexural and Torsional Vibrating Modes. AB - Methods to calculate fluid density and viscosity using a micro-cantilever and based on the resonance principle were put forward. Their measuring mechanisms were analyzed and the theoretical equations to calculate the density and viscosity were deduced. The fluid-solid coupling simulations were completed for the micro-cantilevers with different shapes. The sensing chips with micro cantilevers were designed based on the simulation results and fabricated using the micro electromechanical systems (MEMS) technology. Finally, the MEMS resonant sensor was packaged with the sensing chip to measure the densities and viscosities of eight different fluids under the flexural and torsional vibrating modes separately. The relative errors of the measured densities from 600 kg/m3 to 900 kg/m3 and viscosities from 200 MUPa.s to 1000 MUPa.s were calculated and analyzed with different microcantilevers under various vibrating modes. The experimental results showed that the effects of the shape and vibrating mode of micro-cantilever on the measurement accuracies of fluid density and viscosity were analyzed in detail. PMID- 27275825 TI - Feasibility of Multiple Examinations Using (68)Ga-Labelled Collagelin Analogues: Organ Distribution in Rat for Extrapolation to Human Organ and Whole-Body Radiation Dosimetry. AB - OBJECTIVES: Fibrosis is involved in many chronic diseases. It affects the functionality of vital organs, such as liver, lung, heart and kidney. Two novel imaging agents for positron emission tomography (PET) imaging of fibrosis have previously pre-clinically demonstrated promising target binding and organ distribution characteristics. However, the relevant disease monitoring in the clinical setup would require multiple repetitive examinations per year. Thus, it is of paramount importance to investigate the absorbed doses and total effective doses and thus, the potential maximum number of examinations per year. METHODS: Two cyclic peptide (c[CPGRVMHGLHLGDDEGPC]) analogues coupled via an ethylene glycol linker (EG2) to either 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7 triazonan-1-yl)acetic acid (NO2A-Col) or 4-(4,7-bis(2-(tert-butoxy)-2-oxoethyl) 1,4,7-triazacyclononan-1-yl)-5-(tert-butoxy)-5-oxopentanoic acid (NODAGA-Col) were labelled with (68)Ga. The resulting agents, [(68)Ga]Ga-NO2A-Col and [(68)Ga]Ga-NODAGA-Col, were administered in the tail vein of male and female Sprague-Dawley rats (N = 24). An ex vivo organ distribution study was performed at the 5-, 10-, 20-, 40-, 60- and 120-min time points. The resulting data were extrapolated for the estimation of human organ and total body absorbed and total effective doses using Organ Level Internal Dose Assessment Code software (OLINDA/EXM 1.1) assuming a similar organ distribution pattern between the species. Time-integrated radioactivity in each organ was calculated by trapezoidal integration followed by a single-exponential fit to the data points extrapolated to infinity. The resulting values were used for the residence time calculation. RESULTS: Ex vivo organ distribution data revealed fast blood clearance and washout from most of the organs. Although the highest organ absorbed dose was found for kidneys (0.1 mGy/MBq), this organ was not the dose limiting one and would allow for the administration of over 1460 MBq per year for both [(68)Ga]Ga-NO2A-Col and [(68)Ga]Ga-NODAGA-Col. The total effective dose was the limiting parameter with 0.0155/0.0156 (female/male) mSv/MBq and 0.0164/0.0158 (female/male) mSv/MBq, respectively, for [(68)Ga]Ga-NO2A-Col and [(68)Ga]Ga NODAGA-Col. This corresponded to the total amount of radioactivity that could be administered per year of 643 and 621 MBq before reaching the annual limit of 10 mSv. Thus, up to six examinations would be possible. The residence time and organ absorbed doses in liver and spleen were higher for [(68)Ga]Ga-NODAGA-Col as compared to [(68)Ga]Ga-NO2A-Col. CONCLUSION: The limiting parameter for the administered dose was the total effective dose that would allow for at least six examinations per year that might be sufficient for adequate disease monitoring in longitudinal studies and a routine clinical setup. PMID- 27275826 TI - Enzymatic Hydrolysis of Alginate to Produce Oligosaccharides by a New Purified Endo-Type Alginate Lyase. AB - Enzymatic hydrolysis of sodium alginate to produce alginate oligosaccharides has drawn increasing attention due to its advantages of containing a wild reaction condition, excellent gel properties and specific products easy for purification. However, the efficient commercial enzyme tools are rarely available. A new alginate lyase with high activity (24,038 U/mg) has been purified from a newly isolated marine strain, Cellulophaga sp. NJ-1. The enzyme was most active at 50 degrees C and pH 8.0 and maintained stability at a broad pH range (6.0-10.0) and temperature below 40 degrees C. It had broad substrate specificity toward sodium alginate, heteropolymeric MG blocks (polyMG), homopolymeric M blocks (polyM) and homopolymeric G blocks (polyG), and possessed higher affinity toward polyG (15.63 mM) as well as polyMG (23.90 mM) than polyM (53.61 mM) and sodium alginate (27.21 mM). The TLC and MS spectroscopy analysis of degradation products suggested that it completely hydrolyzed sodium alginate into oligosaccharides of low degrees of polymerization (DPs). The excellent properties would make it a promising tool for full use of sodium alginate to produce oligosaccharides. PMID- 27275827 TI - Nutrient Intakes in Early Life and Risk of Obesity. AB - There is increasing evidence that environmental factors in early life predict later health. The early adiposity rebound recorded in most obese subjects suggests that factors promoting body fat development have operated in the first years of life. Birth weight, growth velocity and body mass index (BMI) trajectories seem to be highly sensitive to the environmental conditions present during pregnancy and in early life ("The first 1000 days"). Particularly, nutritional exposure can have a long-term effect on health in adulthood. The high protein-low fat diet often recorded in young children may have contributed to the rapid rise of childhood obesity prevalence during the last decades. Metabolic programming by early nutrition could explain the development of later obesity and adult diseases. PMID- 27275824 TI - Homogeneous Biosensing Based on Magnetic Particle Labels. AB - The growing availability of biomarker panels for molecular diagnostics is leading to an increasing need for fast and sensitive biosensing technologies that are applicable to point-of-care testing. In that regard, homogeneous measurement principles are especially relevant as they usually do not require extensive sample preparation procedures, thus reducing the total analysis time and maximizing ease-of-use. In this review, we focus on homogeneous biosensors for the in vitro detection of biomarkers. Within this broad range of biosensors, we concentrate on methods that apply magnetic particle labels. The advantage of such methods lies in the added possibility to manipulate the particle labels by applied magnetic fields, which can be exploited, for example, to decrease incubation times or to enhance the signal-to-noise-ratio of the measurement signal by applying frequency-selective detection. In our review, we discriminate the corresponding methods based on the nature of the acquired measurement signal, which can either be based on magnetic or optical detection. The underlying measurement principles of the different techniques are discussed, and biosensing examples for all techniques are reported, thereby demonstrating the broad applicability of homogeneous in vitro biosensing based on magnetic particle label actuation. PMID- 27275828 TI - Individual Characteristics Influencing Physicians' Perceptions of Job Demands and Control: The Role of Affectivity, Work Engagement and Workaholism. AB - The first purpose of the present study was to investigate the role of individual characteristics, i.e., positive and negative affectivity, in explaining the different perception of job control and job demands in a particularly demanding environment such as the healthcare setting. In addition, we aimed to explore the mediational role of work engagement and workaholism using the Job Demands Resources Model as a theoretical framework. Data were collected using a sample of 269 Italian head physicians working in nine general hospitals. To test our hypotheses, the collected data were analyzed with structural equation modeling. Moreover, Sobel Test and bootstrapping were employed to assess the mediating hypotheses. Our results indicated that positive affectivity is related to work engagement, which, in its turn, showed a positive association with job control. In addition, workaholism mediated the relationship between negative affectivity and job demands. All in all, this study represents a first attempt to explore the role of trait affectivity as a dispositional characteristic able to foster the level of work engagement and workaholism exhibited by employees and, in turn, to increase the perceived levels of job control and job demands. PMID- 27275829 TI - Childhood Health Status and Adulthood Cardiovascular Disease Morbidity in Rural China: Are They Related? AB - Cardiovascular diseases (CVDs) are among the top health problems of the Chinese population. Although mounting evidence suggests that early childhood health status has an enduring effect on late life chronic morbidity, no study so far has analyzed the issue in China. Using nationally representative data from the 2013 China Health and Retirement Longitudinal Study (CHARLS), a Probit model and Two Stage Residual Inclusion estimation estimator were applied to analyze the relationship between childhood health status and adulthood cardiovascular disease in rural China. Good childhood health was associated with reduced risk of adult CVDs. Given the long-term effects of childhood health on adulthood health later on, health policy and programs to improve the health status and well-being of Chinese populations over the entire life cycle, especially in persons' early life, are expected to be effective and successful. PMID- 27275830 TI - Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection. AB - Influenza is a serious public health concern worldwide, as it causes significant morbidity and mortality. The emergence of drug-resistant viral strains requires new approaches for the treatment of influenza. In this study, Rubus coreanus seed (RCS) that is left over from the production of wine or juice was found to show antiviral activities against influenza type A and B viruses. Using the time-of addition plaque assay, viral replication was almost completely abolished by simultaneous treatment with the RCS fraction of less than a 1-kDa molecular weight (RCSF1). One of the polyphenols derived from RCSF1, gallic acid (GA), identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against both influenza type A and B viruses, albeit at relatively high concentrations. RCSF1 was bound to hemagglutinin protein, inhibited hemagglutination significantly and disrupted viral particles, whereas GA was found to only disrupt the viral particles by using transmission electron microscopy. In BALB/c mice infected with influenza virus, oral administration of RCSF1 significantly improved the survival rate and reduced the viral titers in the lungs. Our results demonstrate that RCSF1 and GA show potent and broad antiviral activity against influenza A and B type viruses and are promising sources of agents that target virus particles. PMID- 27275831 TI - A Designed "Nested" Dimer of Cyanovirin-N Increases Antiviral Activity. AB - Cyanovirin-N (CV-N) is an antiviral lectin with potent activity against enveloped viruses, including HIV. The mechanism of action involves high affinity binding to mannose-rich glycans that decorate the surface of enveloped viruses. In the case of HIV, antiviral activity of CV-N is postulated to require multivalent interactions with envelope protein gp120, achieved through a pseudo-repeat of sequence that adopts two near-identical glycan-binding sites, and possibly involves a 3D-domain-swapped dimeric form of CV-N. Here, we present a covalent dimer of CV-N that increases the number of active glycan-binding sites, and we characterize its ability to recognize four glycans in solution. A CV-N variant was designed in which two native repeats were separated by the "nested" covalent insertion of two additional repeats of CV-N, resulting in four possible glycan binding sites. The resulting Nested CV-N folds into a wild-type-like structure as assessed by circular dichroism and NMR spectroscopy, and displays high thermal stability with a Tm of 59 degrees C, identical to WT. All four glycan-binding domains encompassed by the sequence are functional as demonstrated by isothermal titration calorimetry, which revealed two sets of binding events to dimannose with dissociation constants Kd of 25 MUM and 900 MUM, assigned to domains B and B' and domains A and A' respectively. Nested CV-N displays a slight increase in activity when compared to WT CV-N in both an anti-HIV cellular assay and a fusion assay. This construct conserves the original binding specifityies of domain A and B, thus indicating correct fold of the two CV-N repeats. Thus, rational design can be used to increase multivalency in antiviral lectins in a controlled manner. PMID- 27275833 TI - Evaluation of the Impact of Mild Steaming and Heat Treatment on the Concentration of Okadaic Acid, Dinophysistoxin-2 and Dinophysistoxin-3 in Mussels. AB - This study explores the effect of laboratory and industrial steaming on mussels with toxin concentrations above and below the legal limit. We used mild conditions for steaming, 100 degrees C for 5 min in industrial processing, and up to 20 min in small-scale laboratory steaming. Also, we studied the effect of heat on the toxin concentration of mussels obtained from two different locations and the effect of heat on the levels of dinophysistoxins 3 (DTX3) in both the mussel matrix and in pure form (7-O-palmitoyl okadaic ester and 7-O-palmytoleyl okadaic ester). The results show that the loss of water due to steaming was very small with a maximum of 9.5%, that the toxin content remained unchanged with no concentration effect or increase in toxicity, and that dinophysistoxins 3 was hydrolyzed or degraded to a certain extent under heat treatment. The use of liquid-certified matrix showed a 55% decrease of dinophysistoxins 3 after 10 min steaming, and a 50% reduction in total toxicity after treatment with an autoclave (121 degrees C for 20 min). PMID- 27275832 TI - Phylogenetic and Molecular Variability Studies Reveal a New Genetic Clade of Citrus leprosis virus C. AB - Citrus leprosis virus C (CiLV-C) causes a severe disease affecting citrus orchards in the Western hemisphere. This study reveals the molecular variability of the virus by analyzing four genomic regions (p29, p15, MP and RNA2-intergenic region) distributed over its two RNAs. Nucleotide diversity (pi) values were relatively low but statistically different over the analyzed genes and subpopulations, indicating their distinct evolutionary history. Values of pip29 and piMP were higher than those of pip15 and piRNA2-IR, whereas piMP was increased due to novel discovered isolates phylogenetically clustered in a divergent clade that we called SJP. Isolate BR_SP_SJP_01 RNA1 and RNA2 sequences, clade SJP, showed an identity of 85.6% and 88.4%, respectively, with those corresponding to CiLV-C, the type member of the genus Cilevirus, and its RNA2 5' proximal region was revealed as a minor donor in a putative inter-clade recombination event. In addition to citrus, BR_SP_SJP_01 naturally infects the weed Commelina benghalensis and is efficiently transmitted by Brevipalpus yothersi mites. Our data demonstrated that negative selection was the major force operating in the evaluated viral coding regions and defined amino acids putatively relevant for the biological function of cilevirus proteins. This work provides molecular tools and sets up a framework for further epidemiological studies. PMID- 27275834 TI - Evaluation of the Toxicity and Toxicokinetics of Cereulide from an Emetic Bacillus cereus Strain of Milk Origin. AB - Bacillus cereus is an opportunistic foodborne agent causing food poisoning and many infectious diseases. The heat-stable emetic toxin cereulide is one of the most prevalent toxins produced by pathogenic B. cereus, resulting in symptoms such as emesis and liver failure. In the present work, the toxicity and toxicokinetics of cereulide from an emetic B. cereus isolate (CAU45) of raw milk were evaluated. The production of cereulide was tested by a cytotoxicity test and enzyme immunoassay, and confirmed by the presence of the ces (cereulide synthetase) gene and the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. All results showed that the amount and toxicity of cereulide produced by CAU45 was 7 to 15.3 folds higher than the reference emetic B. cereus DSMZ 4312. Cereulide in plasma was collected at different time points after a single intravenous injection to evaluate its toxicokinetics in rabbits. The maximum concentration of cereulide was achieved in 2.6 +/- 3.4 h after administration, with the elimination half-life of 10.8 +/- 9.1 h, which expands our understanding of the toxic effects of cereulide. Together, it suggests that urgent sanitary practices are needed to eliminate emetic toxins and emetic B. cereus in raw milk. PMID- 27275836 TI - Molecular Imaging of Angiogenesis and Vascular Remodeling in Cardiovascular Pathology. AB - Angiogenesis and vascular remodeling are involved in a wide array of cardiovascular diseases, from myocardial ischemia and peripheral arterial disease, to atherosclerosis and aortic aneurysm. Molecular imaging techniques to detect and quantify key molecular and cellular players in angiogenesis and vascular remodeling (e.g., vascular endothelial growth factor and its receptors, alphavbeta3 integrin, and matrix metalloproteinases) can advance vascular biology research and serve as clinical tools for early diagnosis, risk stratification, and selection of patients who would benefit most from therapeutic interventions. To target these key mediators, a number of molecular imaging techniques have been developed and evaluated in animal models of angiogenesis and vascular remodeling. This review of the state of the art molecular imaging of angiogenesis and vascular (and valvular) remodeling, will focus mostly on nuclear imaging techniques (positron emission tomography and single photon emission tomography) that offer high potential for clinical translation. PMID- 27275835 TI - A Role for the Intestinal Microbiota and Virome in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)? AB - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous disorder of significant societal impact that is proposed to involve both host and environmentally derived aetiologies that may be autoimmune in nature. Immune related symptoms of at least moderate severity persisting for prolonged periods of time are common in ME/CFS patients and B cell depletion therapy is of significant therapeutic benefit. The origin of these symptoms and whether it is infectious or inflammatory in nature is not clear, with seeking evidence of acute or chronic virus infections contributing to the induction of autoimmune processes in ME/CFS being an area of recent interest. This article provides a comprehensive review of the current evidence supporting an infectious aetiology for ME/CFS leading us to propose the novel concept that the intestinal microbiota and in particular members of the virome are a source of the "infectious" trigger of the disease. Such an approach has the potential to identify disease biomarkers and influence therapeutics, providing much-needed approaches in preventing and managing a disease desperately in need of confronting. PMID- 27275838 TI - Detection of Volatile Metabolites of Garlic in Human Breast Milk. AB - The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo analytically using gas chromatography-mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences. PMID- 27275839 TI - Right Anterolateral Minithoracotomy versus Median Sternotomy Approach for Resection of Left Atrial Myxoma. AB - BACKGROUND: Minimally invasive surgery has become the standard approach for several cardiac diseases. In this retrospective study, we compared right anterolateral minithoracotomy (RALT) with standard median sternotomy (SMS) for resection of left atrial myxoma (LAM). MATERIALS AND METHODS: From January 2009 to June 2015, the clinical data of patients who underwent RALT (n = 30) and SMS (n = 36) for resection of LAM in our hospital were collected. The preoperative clinical data and operative results were compared between the two groups. RESULTS: There were no significant differences in aortic cross-clamp and cardiopulmonary bypass time between the two groups. The total incision length was significantly shorter in RALT group compared with SMS group (p < 0.001). For RALT and SMS groups, respectively, the intensive care unit length of stay was 29.2 +/- 6.5 versus 43.5 +/- 6.9 hours (p < 0.001), and the postoperative hospital length of stay was 5 days (interquartile range [IQR]: 4-6) versus 8 days (IQR: 7-10) (p < 0.001). The total cost in RALT group was 27,000 RMB (IQR: 25,000-29,000) versus 33,000 RMB (IQR: 31,000-35,000) in SMS group (p < 0.001). There were no significant differences in mortality and postoperative complications between the two groups. CONCLUSION: RALT approach for LAM resection can be performed safely with favorable cosmetic outcome, accepted clinical results, and lower cost. It should be considered as a promising alternative to SMS and merit additional study. PMID- 27275837 TI - Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine. AB - Stroke is one of the major causes of death and adult disability worldwide. The underlying pathophysiology of stroke is highly complicated, consisting of impairments of multiple signalling pathways, and numerous pathological processes such as acidosis, glutamate excitotoxicity, calcium overload, cerebral inflammation and reactive oxygen species (ROS) generation. The current treatment for ischemic stroke is limited to thromolytics such as recombinant tissue plasminogen activator (tPA). tPA has a very narrow therapeutic window, making it suitable to only a minority of stroke patients. Hence, there is great urgency to develop new therapies that can protect brain tissue from ischemic damage. Recent studies have shown that new vessel formation after stroke not only replenishes blood flow to the ischemic area of the brain, but also promotes neurogenesis and improves neurological functions in both animal models and patients. Therefore, drugs that can promote angiogenesis after ischemic stroke can provide therapeutic benefits in stroke management. In this regard, Chinese herbal medicine (CHM) has a long history in treating stroke and the associated diseases. A number of studies have demonstrated the pro-angiogenic effects of various Chinese herbs and herbal formulations in both in vitro and in vivo settings. In this article, we present a comprehensive review of the current knowledge on angiogenesis in the context of ischemic stroke and discuss the potential use of CHM in stroke management through modulation of angiogenesis. PMID- 27275840 TI - Rapid Isolation of Staphylococcus aureus Pathogens from Infected Clinical Samples Using Magnetic Beads Coated with Fc-Mannose Binding Lectin. AB - Here we describe how Staphylococcus aureus bacteria can be rapidly isolated from clinical samples of articular fluid and synovial tissue using magnetic beads coated with the engineered chimeric human opsonin protein, Fc-mannose-binding lectin (FcMBL). The FcMBL-beads were used to capture and magnetically remove bacteria from purified cultures of 12 S. aureus strains, and from 8 articular fluid samples and 4 synovial tissue samples collected from patients with osteoarthritis or periprosthetic infections previously documented by positive S. aureus cultures. While the capture efficiency was high (85%) with purified S. aureus strains grown in vitro, direct FcMBL-bead capture from the clinical samples was initially disappointing (< 5% efficiency). Further analysis revealed that inhibition of FcMBL binding was due to coating of the bacteria by immunoglobulins and immune cells that masked FcMBL binding sites, and to the high viscosity of these complex biological samples. Importantly, capture of pathogens using the FcMBL-beads was increased to 76% efficiency by pretreating clinical specimens with hypotonic washes, hyaluronidase and a protease cocktail. Using this approach, S. aureus bacteria could be isolated from infected osteoarthritic tissues within 2 hours after sample collection. This FcMBL-enabled magnetic method for rapid capture and concentration of pathogens from clinical samples could be integrated upstream of current processes used in clinical microbiology laboratories to identify pathogens and perform antibiotic sensitivity testing when bacterial culture is not possible or before colonies can be detected. PMID- 27275841 TI - Trimethylation Enhancement Using (13)C-Diazomethane ((13)C-TrEnDi): Increased Sensitivity and Selectivity of Phosphatidylethanolamine, Phosphatidylcholine, and Phosphatidylserine Lipids Derived from Complex Biological Samples. AB - Significant sensitivity enhancements in the tandem mass spectrometry-based analysis of complex mixtures of several phospholipid classes has been achieved via (13)C-TrEnDi. (13)C-TrEnDi-modified phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylcholine (PC) lipids extracted from HeLa cells demonstrated greater sensitivity via precursor ion scans (PISs) than their unmodified counterparts. Sphingomyelin (SM) species exhibited neither an increased nor decreased sensitivity following modification. The use of isotopically labeled diazomethane enabled the distinction of modified PE and modified PC species that would yield isobaric species with unlabeled diazomethane. (13)C-TrEnDi created a PE-exclusive PIS of m/z 202.1, two PS exclusive PISs of m/z 148.1 and m/z 261.1, and a PIS of m/z 199.1 for PC species (observed at odd m/z values) and SM species (observed at even m/z values). The standardized average area increase after TrEnDi modification was 10.72-fold for PE species, 2.36-fold for PC, and 1.05-fold for SM species. The sensitivity increase of PS species was not quantifiable, as there were no unmodified PS species identified prior to derivatization. (13)C-TrEnDi allowed for the identification of 4 PE and 7 PS species as well as the identification and quantitation of an additional 4 PE and 4 PS species that were below the limit of detection (LoD) prior to modification. (13)C-TrEnDi also pushed 24 PE and 6 PC lipids over the limit of quantitation (LoQ) that prior to modification were above the LoD only. PMID- 27275842 TI - Balancing Water Uptake and Loss through the Coordinated Regulation of Stomatal and Root Development. AB - Root development is influenced by nutrient and water availabilities. Plants are able to adjust many attributes of their root in response to environmental signals including the size and shape of the primary root, lateral roots and root hairs. Here we investigated the response of roots to changes in the levels of leaf transpiration associated with altered stomatal frequency. We found that plants with high stomatal density and conductance produce a larger rooting area and as a result have enhanced phosphate uptake capacity whereas plants with low stomatal conductance produce a smaller root. Manipulating the growth environment of plants indicated that enhanced root growth is most likely a result of an increased demand for water rather than phosphate. Plants manipulated to have an increase or reduction in root hair growth show a reduction or increase respectively, in stomatal conductance and density. Our results demonstrate that plants can balance their water uptake and loss through coordinated regulation of both stomatal and root development. PMID- 27275843 TI - Cardiovascular effects of urocortin 2 and urocortin 3 in patients with chronic heart failure. AB - AIMS: Urocortin 2 and urocortin 3 may play a role in the pathophysiology of heart failure and are emerging therapeutic targets. We aimed to examine the local and systemic cardiovascular effects of urocortin 2 and urocortin 3 in healthy subjects and patients with heart failure. METHODS: Patients with heart failure (n = 8) and age and gender-matched healthy subjects (n = 8) underwent bilateral forearm arterial blood flow measurement using forearm venous occlusion plethysmography during intra-arterial infusions of urocortin 2 (3.6-36 pmol min( 1) ), urocortin 3 (360-3600 pmol min(-1) ) and substance P (2-8 pmol min(-1) ). Heart failure patients (n = 9) and healthy subjects (n = 7) underwent non invasive impedance cardiography during incremental intravenous infusions of sodium nitroprusside (573-5730 pmol kg(-1) min(-1) ), urocortin 2 (36-360 pmol min(-1) ), urocortin 3 (1.2-12 nmol min(-1) ) and saline placebo. RESULTS: Urocortin 2, urocortin 3 and substance P induced dose-dependent forearm arterial vasodilatation in both groups (P < 0.05 for both) with no difference in magnitude of vasodilatation between patients and healthy subjects. During systemic intravenous infusions, urocortin 3 increased heart rate and cardiac index and reduced mean arterial pressure and peripheral vascular resistance index in both groups (P < 0.01 for all). Urocortin 2 produced similar responses to urocortin 3, although increases in cardiac index and heart rate were only significant in heart failure (P < 0.05) and healthy subjects (P < 0.001), respectively. CONCLUSION: Urocortins 2 and 3 cause vasodilatation, reduce peripheral vascular resistance and increase cardiac output in both health and disease. These data provide further evidence to suggest that urocortins 2 and 3 continue to hold promise for the treatment of heart failure. PMID- 27275845 TI - The Candida albicans fimbrin Sac6 regulates oxidative stress response (OSR) and morphogenesis at the transcriptional level. AB - The actin cytoskeleton coordinates numerous fundamental cellular processes. Fimbrins are a class of evolutionally conserved ABPs that mediate actin bundling and regulate actin dynamics and functions. In this study, we identified the fimbrin Sac6 from the important fungal pathogen, Candida albicans. Interestingly, deletion of SAC6 led to increased tolerance to oxidative stress, while its overexpression caused hyper-susceptibility to this stress. Further investigations revealed that Sac6, by interaction with actin, negatively regulated the cytosol to-nucleus transport of the key OSR (oxidative stress response) transcription factor Cap1 and consequent expression of OSR genes. Moreover, loss of Sac6 enhanced hyphal maintenance, and its overexpression caused a defect in hyphal development, which was attributed to abnormal expression of morphogenesis-related genes. In addition, Sac6 was involved in regulation of secretion of lytic enzymes and virulence of C. albicans. This study reveals a novel mechanism by which fimbrin transcriptionally regulates OSR and morphogenesis, and sheds a novel light on the functions of actin cytoskeleton. PMID- 27275846 TI - Comparative analysis of two bacteriophages of Xanthomonas arboricola pv. juglandis. AB - Walnut blight caused by Xanthomonas arboricola pv. juglandis (Xaj) is one of the most frequent infective diseases of walnut, resulting in serious economic losses. One potential solution to control this disease could be the application of bacteriophages. In this study, 24 phages were isolated from soil and walnut aerial tissues infected with Xaj. Two polyvalent bacteriophages, Xaj2 and Xaj24 were chosen for further characterization including their morphological, physiological and genomic analyses. Xaj2 was classified as Siphoviridae whereas Xaj24 belonged to the Podoviridae family. Both phages demonstrated lytic effect on Xaj in laboratory trials. Complete genomes of Xaj2 and Xaj24 were determined. Genomes of Xaj2 and Xaj24 consisted of 49.241 and 44.861 nucleotides encoding 80 and 53 genes, respectively. Comparative genome analyses have revealed that Xaj2 had a unique genome sequence, while Xaj24 was a phiKMV-like phage and it was most similar to the Prado phage which is virulent for Xylella fastidiosa and Xanthomonas spp. In this study, we present the first two complete Xaj phage sequences enabling an insight into the genomics of Xaj phages. PMID- 27275844 TI - Self-Care for Management of Secondary Lymphedema: A Systematic Review. AB - BACKGROUND: Lymphedema is a debilitating and disfiguring sequela of an overwhelmed lymphatic system. The most common causes of secondary lymphedema are lymphatic filariasis (LF), a vector-borne, parasitic disease endemic in 73 tropical countries, and treatment for cancer in developed countries. Lymphedema is incurable and requires life-long care so identification of effective lymphedema management is imperative to improve quality of life, reduce the burden on family resources and benefit the local community. This review was conducted to evaluate the evidence for effective lymphedema self-care strategies that might be applicable to management of all types of secondary lymphedema. METHODOLOGY/PRINCIPAL FINDINGS: Searches were conducted in Medline, CINAHL and Scopus databases in March 2015. Included studies reported before and after measures of lymphedema status or frequency of acute infections. The methodological quality was assessed using the appropriate Critical Appraisal Skills Program checklist. Descriptive synthesis and meta-analysis were used to evaluate effectiveness of the outcomes reported. Twenty-eight papers were included; two RCTs were found to have strong methodology, and overall 57% of studies were rated as methodologically weak. Evidence from filariasis-related lymphedema (FR-LE) studies indicated that hygiene-centred self-care reduced the frequency and duration of acute episodes by 54%, and in cancer-related lymphedema (CR-LE) home-based exercise including deep breathing delivered significant volume reductions over standard self-care alone. Intensity of training in self-care practices and frequency of monitoring improved outcomes. Cultural and economic factors and access to health care services influenced the type of intervention delivered and how outcomes were measured. CONCLUSIONS/SIGNIFICANCE: There is evidence to support the adoption of remedial exercises in the management of FR-LE and for a greater emphasis on self-treatment practices for people with CR-LE. Empowerment of people with lymphedema to care for themselves with access to supportive professional assistance has the capacity to optimise self-management practices and improve outcomes from limited health resources. PMID- 27275847 TI - Phylodynamics of influenza A(H3N2) in South America, 1999-2012. AB - The limited influenza A(H3N2) genetic data available from the Southern Hemisphere (particularly from Africa and Latin America), constrains the accurate reconstruction of viral dissemination dynamics within those regions. Our objective was to describe the spatial dissemination dynamics of influenza A(H3N2) within South America. A total of 469 sequences of the HA1 portion of the hemagglutinin gene (HA) from influenza A(H3N2) viruses sampled in temperate and tropical South American countries between 1999 and 2012 were combined with available contemporary sequences from Australia, Hong Kong, United Kingdom and the United States. Phylogenetic analyses revealed that influenza A(H3N2) sequences from South America were highly intermixed with sequences from other geographical regions, although a clear geographic virus population structure was detected globally. We identified 14 clades mostly (>=80%) composed of influenza sequences from South American countries. Bayesian phylogeographic analyses of those clades support a significant role of both temperate and tropical regions in the introduction and dissemination of new influenza A(H3N2) strains within South America and identify an intensive bidirectional viral exchange between different geographical areas. These findings indicate that seasonal influenza A(H3N2) epidemics in South America are seeded by both the continuous importation of viral variants from other geographic regions and the short-term persistence of local lineages. This study also supports a complex metapopulation model of influenza A(H3N2) dissemination in South America, with no preferential direction in viral movement between temperate and tropical regions. PMID- 27275848 TI - Daytime warming lowers community temporal stability by reducing the abundance of dominant, stable species. AB - Daytime warming and nighttime warming have the potential to influence plant community structure and ecosystem functions. However, their impacts on ecological stability remain largely unexplored. We conducted an eight-year field experiment to compare the effects of daytime and nighttime warming on the temporal stability of a temperate steppe in northern China. Our results showed that the cover and stability of dominant species, stability of subordinate species, and compensatory dynamics among species strongly influenced community-level stability. However, daytime, but not nighttime, warming significantly reduced community temporal stability mainly through the reduction in the abundance of dominant, stable species. These findings demonstrate the differential effects of daytime and nighttime warming on community stability and emphasize the importance of understanding the changes of dominant species for accurately predicting community dynamics under climate warming. PMID- 27275849 TI - Characteristics of the fibroplasia and collagen expression in the abdominal wall after implant of the polypropylene mesh and polypropylene/polyglecaprone mesh in rats. AB - PURPOSE: To compare fibroplasia and the resistance of the abdominal wall when polypropylene meshes and polypropylene/poliglecaprone are used. METHODS: Seventy seven male Wistar rats were divided into three groups: Control Group (for resistance); Group E (polypropylene mesh); and Group U (polypropylene/poliglecaprone mesh). The animals in Groups E and U had a standard muscular and aponeurotic defect, with integral peritoneum, and correction with the mesh. Measurements were taken 4, 7, 14, 28 and 56 days after surgery. The resistance, and collagen density were studied. RESULTS: Resistance on the 56th day was similar in both meshes. The gain in resistance described an ascending curve for the polypropylene mesh and was irregular in the case of the polypropylene/poliglecaprone. Fibroplasia showed a gain in type I and type III collagen in both groups (p<0.001). Collagen III stabilized in the 14th day and collagen I continued to ascend. CONCLUSIONS: The gain in resistance of the polypropylene mesh is regular and ascending, whereas the polypropylene/poliglecaprone is not regular. The final resistance of both meshes is similar; the collagen density increases over time, and show the same inflammatory potential. PMID- 27275850 TI - Simvastatin and biphasic calcium phosphate affects bone formation in critical sized rat calvarial defects. AB - PURPOSE: To investigate the effects of locally applied simvastatin plus biphasic calcium phosphate (BoneCeramic(r)) or collagen sponge on bone formation in critical-sized bone defects. METHODS: Thirty defects of 5mm in diameter were created bilaterally with a trephine bur in the calvariae of fifteen Wistar rats. The defects were divided into five groups: group 1 - control, no treatment; group 2 (BoneCeramic(r)); group 3 (BoneCeramic(r) + 0.1mg simvastatin); group 4 (collagen sponge); and group 5 (collagen sponge + 0.1mg simvastatin). After eight weeks the animals were euthanized and their calvariae were histologically processed. Hematoxylin and eosin-stained sections were subjected to histological and histomorphometrical analyses. The area of newly formed bone was calculated and compared between groups. RESULTS: The greater amount of a bone-like tissue was formed around the carrier in group 3 (BoneCeramic(r) + 0.1mg simvastatin) followed by group 2 (BoneCeramic(r)), and almost no bone was formed in the other groups. Group 3 was significantly different compared to group 2, and both groups were significantly different compared to the other groups. CONCLUSION: Simvastatin combined with BoneCeramic(r) induced significantly greater amounts of newly formed bone and has great potential for the healing of bone defects. PMID- 27275851 TI - Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model. AB - PURPOSE : To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration. METHODS: Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35MUg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II - control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylin-eosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci. RESULTS: Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p<=0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p<=0.001). In the control group, all animals presented the chronology of a normal wound healing. CONCLUSIONS: The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ. PMID- 27275852 TI - Effects of platelet rich plasma on fascial healing in rats with fecal peritonitis AB - PURPOSE: To evaluate the effects of platelet rich plasma (PRP) on the healing of fascia wherein peritonitis has been created. METHODS: Twenty eight Wistar Albino rats were divided into four groups. Only a primary fascial repair following laparotomy was performed on Group 1, a primary fascial repair performed and PRP treatment applied following laparotomy on Group 2, and a fecal peritonitis created following laparotomy and a primary fascial repair carried out on Group 3. A fecal peritonitis was created following laparotomy and primary fascial repair and PRP treatment on the fascia was carried out on Group 4. RESULTS: TNF-alpha was found to be significantly lower in the control group (Group 1). It was detected at the highest level in the group in which fecal peritonitis was created and PRP applied (Group 4). TGF-beta was determined as being significantly higher only in Group 4. Histopathologically, the differences between the groups in terms of cell infiltration and collagen deposition were not found to be significant. CONCLUSION: When platelet rich plasma was given histologically and biochemicaly as wound healing parameters cellular infiltration, collagen accumulation, and tissue hydroxyiproline levels were not increased but neovascularization, fibroblast activation and TNF Alfa levels were increased and PRP accelerated wound healing. PMID- 27275853 TI - Immediate postoperative evaluation of enteric anastomosis after the use of meloxicam in rats AB - PURPOSE: To compare ileal anastomoses in the immediate postoperative healing period after meloxicam use. METHODS: Forty two male Wistar rats were randomly divided into two groups of 21, COX and control group. To COX meloxicam in combination with morphine was given in 3 days period. Control group received only morphine during the same period. Each group was divided into three sub-groups of 7, which were euthanized at 5, 10, and 21 days postoperatively. Comparison was based in histological evaluation of collagen type I and III using sirius red, immunohistochemical through vascular endothelial growth factor and matrix metalloproteinase-9. RESULTS: Healing process in scheduled periods did not show significant differences (p>0.05) between the COX and control groups during any of the periods. CONCLUSION: The use of meloxicam in the postoperative period following ileal anastomosis did not affect healing. PMID- 27275854 TI - Antibacterial properties and healing effects of Melipona scutellaris honey in MRSA-infected wounds of rats. AB - PURPOSE : To investigate the antimicrobial, immunological and healing effects of Melipona scutellaris honey on infected wounds of rat skin. METHODS: Twenty four Wistar rats were distributed in four groups (6-each). The uninfected skin wounds of group I rats were treated daily with saline for 7 days. Uninfected wounds (group II) rats were treated with honey. In group III (treated with saline) and group IV (treated with honey) wounds were inoculated with MRSA ATTC43300. The first bacterial culture was performed 24 hours later. In the 7th day new culture was done, and wound biopsies were used for cytokines dosage and histopathology. RESULTS: In group I and III rats the CFU/g count of S. aureus in wounds was zero. In group II rats the CFU/g counts in the wound tissue were significantly higher than in wounds of group IV rats. The density histopathological parameters and the expression of TNF-alpha, IL1-beta, Il-6 were significantly higher on wounds of group IV then in the other groups. CONCLUSION: Honey of Melipona scutellaris was effective in the management of infected wounds, by significant bacterial growth inhibition, enhancement of cytokine expression, and positively influenced the wound repair. PMID- 27275855 TI - Direct intraperitoneal resuscitation with lidocaine, methylene blue and pentoxiphylline combination does not decreases inflammation after intestinal ischemia-reperfusion injury in rats. AB - PURPOSE: To evaluate the effects of an intraperitoneal solution of methylene blue (MB), lidocaine and pentoxyphylline (PTX) on intestinal ischemic and reperfusion injury. METHODS: Superior mesenteric artery was isolated and clamped in 36 adult male Sprague Dawley rats. After 60 minutes, clamp was removed and a group received intraperitoneally UNITO solution (PTX 25mg/kg + lidocaine 5mg/kg + MB 2mg/kg), while the other group was treated with warm 0.9% NaCl solution. Rats were euthanized 45 min after drug administration. Lung and bowel were collected for histological evaluation (using Park's score) and determination of myeloperoxidase (MPO) and malondialdehyde (MDA) levels. RESULTS: Control samples showed lymphoplasmocytic infiltrate and crypt necrosis of villi. MPO and MDA measurements shown no differences between treated and control groups. CONCLUSION: The combination of lidocaine, methylene blue and pentoxyphylline administered intraperitoneally at the studied dose, did not decreased histological lesion scores and biochemical markers levels in intestinal ischemia/reperfusion injury. PMID- 27275856 TI - Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats. AB - PURPOSE: To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia reperfusion. METHODS: Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. RESULTS: The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. CONCLUSION: Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period. PMID- 27275857 TI - Quantitative analysis of the renal aging in rats. Stereological study. AB - PURPOSE: To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. METHODS: Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. RESULTS: There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. CONCLUSIONS: The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process. PMID- 27275858 TI - Chest drainage teaching and training for medical students. Use of a surgical ex vivo pig model. AB - PURPOSE: Implement a constructivist approach in thoracic drainage training in surgical ex vivo pig models, to compare the acquisition of homogeneous surgical skills between medical students. METHODS: Experimental study, prospective, transversal, analytical, controlled, three steps. Selection, training, evaluation. INCLUSION CRITERIA: a) students without training in thoracic drainage; b) without exposure to constructivist methodology. 2) EXCLUSION CRITERIA: a) students developed surgical skills; b) a history of allergy. (N = 312). Two groups participated in the study: A and B. Lecture equal for both groups. Differentiated teaching: group A, descriptive and informative method; group B, learning method based on problems. A surgical ex vivo pig model for training the chest drain was created. Were applied pre and post-test, test goal discursive and OSATS scale. RESULTS: Theoretical averages: Group A = 9.5 +/- 0.5; Group B = 8.8 +/- 1.1 (p = 0.006). Medium Practices: Group A = 22.8 +/- 1.8; Group B = 23.0 +/- 2.8 (p <0.001). CONCLUSION: Through the constructivist methodology implemented in the thoracic drainage training in surgical ex vivo pig models, has proven the acquisition of surgical skills homogeneous compared among medical students. PMID- 27275859 TI - High-dose omeprazole infusion compared with scheduled second-look endoscopy for prevention of peptic ulcer rebleeding: a randomized controlled trial. AB - BACKGROUND AND STUDY AIM: Previous studies have shown that both scheduled second look endoscopy and high-dose continuous omeprazole infusion are effective in preventing peptic ulcer rebleeding. The aim of this noninferiority trial was to compare the efficacy of these two strategies for the prevention of rebleeding following primary endoscopic hemostasis. PATIENTS AND METHODS: Consecutive patients who received endoscopic treatment for bleeding peptic ulcers (actively bleeding, with nonbleeding visible vessels) were randomized to two treatment groups following hemostasis. One group (second-look endoscopy group) received the proton pump inhibitor (PPI) omeprazole as an intravenous bolus every 12 hours for 72 hours and a second endoscopy within 16 - 24 hours with retreatment for persistent stigmata of bleeding. The other group (PPI infusion group) received continuous high-dose omeprazole infusion for 72 hours. Patients who developed rebleeding underwent surgery if repeat endoscopic therapy failed. The primary outcome was the rebleeding rate within 30 days after initial hemostasis. The margin for noninferiority was set at 5 %. RESULTS: A total of 153 patients were randomized to the PPI infusion group and 152 to the second-look endoscopy group. Rebleeding occurred within 30 days in 10 patients (6.5 %) in the PPI infusion group and in 12 patients (7.9 %) in the second-look endoscopy group (P = 0.646). Surgery was required for rebleeding in six patients from the PPI infusion group and three patients in the second-look endoscopy group (P = 0.32). Intensive care unit stay, transfusion requirements, and mortality were not different between the groups. Patients in the second-look endoscopy group were discharged 1 day earlier than those in the PPI infusion group (P < 0.001). CONCLUSIONS: After endoscopic hemostasis, high-dose PPI infusion was not inferior to second-look endoscopy with bolus PPI in preventing peptic ulcer rebleeding. TRIAL REGISTRATION: ClinicalTrials.gov (NCT: 00164931). PMID- 27275860 TI - Quality of optical diagnosis of diminutive polyps and associated factors. AB - BACKGROUND AND AIMS: The aim of the study was to identify endoscopist-related and procedural factors that may be associated with the quality of optical diagnosis of diminutive polyps using narrow-band imaging (NBI). METHODS: All subjects who participated in a randomized trial on cap-assisted colonoscopy were eligible for the current study. Optical polyp diagnosis was an a priori outcome of the initial trial. Ten participating endoscopists used NBI to assess all of the diagnosed polyps as adenomatous or non-adenomatous in real-time and provided a degree of diagnostic certainty. The main outcome measures were quality benchmarks of optical diagnosis (negative predictive value [NPV] for diminutive rectosigmoid adenomas, agreement with pathology-based surveillance interval) and assessment of endoscopist-related and procedural factors potentially associated with the quality of optical diagnosis. RESULTS: A total of 1650 polyps were found in 607 patients, with 1311 polyps (79 %) being diminutive, of which 672 (53 %) were adenomatous. The NPV of optical diagnosis for rectosigmoid adenomas was 95 %. The optical diagnosis-based surveillance interval agreed with the pathology-based recommendation in 93 % of patients. Prior experience with image-enhanced endoscopy had no effect on optical diagnosis. Low and high adenoma detectors were not different in achieving the quality benchmarks. Cap-assisted colonoscopy was not associated with quality of optical diagnosis. Quality metrics of optical diagnosis remained similar during the first and second half of the study period. CONCLUSION: High quality optical diagnosis of diminutive polyps can be achieved and sustained by endoscopists previously inexperienced in this practice with minimal training. None of the examined factors appear to affect the quality of optical diagnosis; particularly, endoscopists' adenoma detection was not associated with optical diagnosis. PMID- 27275861 TI - Combined ovulation triggering with GnRH agonist and hCG in IVF patients. AB - The aim of the review is to analyse the combination of a gonadotrophin releasing hormone (GnRH) agonist with a human chorionic gonadotrophin (hCG) trigger, for final oocyte maturation in in vitro fertilisation (IVF) cycles. The concept being a ''dual trigger'' combines a single dose of the GnRH agonist with a reduced or standard dosage of hCG at the time of triggering. The use of a GnRH agonist with a reduced dose of hCG in high responders demonstrated luteal phase support with improved pregnancy rates, similar to those after conventional hCG and a low risk of ovarian hyperstimulation syndrome (OHSS). The administration of a GnRH agonist and a standard hCG in normal responders, demonstrated significantly improved live birth rates and a higher number of embryos of excellent quality, or cryopreserved embryos. The concept of the ''double trigger" represents a combination of a GnRH agonist and a standard hCG, when used 40 and 34 h prior to ovum pick-up, respectively. The use of the ''double trigger" has been successfully offered in the treatment of empty follicle syndrome and in patients with a history of immature oocytes retrieved or with low/poor oocytes yield. Further prospective studies are required to confirm the aforementioned observations prior to clinical implementation. PMID- 27275862 TI - Propane Clathrate Hydrate Formation Accelerated by Methanol. AB - The role of methanol as both an inhibitor and a catalyst for the formation of clathrate hydrates (CHs) has been a topic of intense study. We report a new quantitative study of the kinetics of propane CH formation at 253 K from the reaction of propane gas with <75 MUm ice particles that have been doped with varying amounts of methanol. We find that methanol significantly accelerates the formation reaction with quite small doping quantities. Even for only 1 methanol molecule per 10 000 water molecules, the maximum uptake rate of propane into CHs is enhanced and the initiation pressure is reduced. These results enable more efficient production of CHs for gas storage. This remarkable acceleration of the CH formation reaction by small quantities of methanol may place constraints on the mechanism of the inhibition effect observed under other conditions, usually employing much larger quantities of methanol. PMID- 27275863 TI - The H-ATOMIC Criteria for the Etiologic Classification of Patients with Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: There are no generally accepted criteria for the etiologic classification of intracerebral hemorrhage (ICH). For this reason, we have developed a set of etiologic criteria and have applied them to a large number of patients to determine their utility. METHODS: The H-ATOMIC classification includes 7 etiologic categories: Hypertension, cerebral Amyloid angiopathy, Tumour, Oral anticoagulants, vascular Malformation, Infrequent causes and Cryptogenic. For each category, the etiology is scored with three degrees of certainty: Possible(3), Probable(2) and Definite(1). Our aim was to perform a basic study consisting of neuroimaging, blood tests, and CT-angio when a numerical score (SICH) suggested an underlying structural abnormality. Combinations of >1 etiologic category for an individual patient were acceptable. The criteria were evaluated in a multicenter and prospective study of consecutive patients with spontaneous ICH. RESULTS: Our study included 439 patients (age 70.8 +/- 14.5 years; 61.3% were men). A definite etiology was achieved in 176 (40.1% of the patients: Hypertension 28.2%, cerebral Amyloid angiopathy 0.2%, Tumour 0.2%, Oral anticoagulants 2.2%, vascular Malformation 4.5%, Infrequent causes 4.5%). A total of 7 patients (1.6%) were cryptogenic. In the remaining 58.3% of the patients, ICH was attributable to a single (n = 56, 12.7%) or the combination of >=2 (n = 200, 45.5%) possible/probable etiologies. The most frequent combinations of etiologies involved possible hypertension with possible CAA (H3A3, n = 38) or with probable CAA (H3A2, n = 29), and probable hypertension with probable OA (H2O2, n = 27). The most frequent category with any degree of certainty was hypertension (H1+2+3 = 80.6%) followed by cerebral amyloid angiopathy (A1+2+3 = 30.9%). CONCLUSIONS: According to our etiologic criteria, only about 40% patients received a definite diagnosis, while in the remaining patients ICH was attributable to a single possible/probable etiology or to more than one possible/probable etiology. The use of these criteria would likely help in the management of patients with ICH. PMID- 27275864 TI - Antioxidative Activities of Both Oleic Acid and Camellia tenuifolia Seed Oil Are Regulated by the Transcription Factor DAF-16/FOXO in Caenorhabditis elegans. AB - BACKGROUND: Tea seed oil is a high quality edible oil, yet lacking sufficient scientific evidences to support the nutritional and medical purposes. We identified major and minor components in Camellia tenuifolia seed oil and investigated the antioxidative activity and its underlying mechanisms in Caenorhabditis elegans. PRINCIPAL FINDINGS: The results showed that the major constitutes in C. tenuifolia seed oil were unsaturated fatty acids (~78.4%). Moreover, two minor compounds, beta-amyrin and beta-sitosterol, were identified and their antioxidative activity was examined. We found that oleic acid was the major constitute in C. tenuifolia seed oil and plays a key role in the antioxidative activity of C. tenuifolia seed oil in C. elegans. CONCLUSIONS: This study found evidences that the transcription factor DAF-16/FOXO was involved in both oleic acid- and C. tenuifolia seed oil-mediated oxidative stress resistance in C. elegans. This study suggests the potential of C. tenuifolia seed oil as nutrient or functional foods. PMID- 27275865 TI - Enzyme Substrate Complex of the H200C Variant of Homoprotocatechuate 2,3 Dioxygenase: Mossbauer and Computational Studies. AB - The extradiol, aromatic ring-cleaving enzyme homoprotocatechuate 2,3-dioxygenase (HPCD) catalyzes a complex chain of reactions that involve second sphere residues of the active site. The importance of the second-sphere residue His200 was demonstrated in studies of HPCD variants, such as His200Cys (H200C), which revealed significant retardations of certain steps in the catalytic process as a result of the substitution, allowing novel reaction cycle intermediates to be trapped for spectroscopic characterization. As the H200C variant largely retains the wild-type active site structure and produces the correct ring-cleaved product, this variant presents a valuable target for mechanistic HPCD studies. Here, the high-spin Fe(II) states of resting H200C and the H200C homoprotocatechuate enzyme-substrate (ES) complex have been characterized with Mossbauer spectroscopy to assess the electronic structures of the active site in these states. The analysis reveals a high-spin Fe(II) center in a low symmetry environment that is reflected in the values of the zero-field splitting (ZFS) (D ~ - 8 cm(-1), E/D ~ 1/3 in ES), as well as the relative orientations of the principal axes of the (57)Fe magnetic hyperfine (A) and electric field gradient (EFG) tensors relative to the ZFS tensor axes. A spin Hamiltonian analysis of the spectra for the ES complex indicates that the magnetization axis of the integer spin S = 2 Fe(II) system is nearly parallel to the symmetry axis, z, of the doubly occupied dxy ground orbital deduced from the EFG and A-values, an observation, which cannot be rationalized by DFT assisted crystal-field theory. In contrast, ORCA/CASSCF calculations for the ZFS tensor in combination with DFT calculations for the EFG- and A-tensors describe the experimental data remarkably well. PMID- 27275867 TI - The Global Rise of Zero Liquid Discharge for Wastewater Management: Drivers, Technologies, and Future Directions. AB - Zero liquid discharge (ZLD)-a wastewater management strategy that eliminates liquid waste and maximizes water usage efficiency - has attracted renewed interest worldwide in recent years. Although implementation of ZLD reduces water pollution and augments water supply, the technology is constrained by high cost and intensive energy consumption. In this critical review, we discuss the drivers, incentives, technologies, and environmental impacts of ZLD. Within this framework, the global applications of ZLD in the United States and emerging economies such as China and India are examined. We highlight the evolution of ZLD from thermal- to membrane-based processes, and analyze the advantages and limitations of existing and emerging ZLD technologies. The potential environmental impacts of ZLD, notably greenhouse gas emission and generation of solid waste, are discussed and the prospects of ZLD technologies and research needs are highlighted. PMID- 27275866 TI - Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid Phase Uptake through Distinct Mechanisms. AB - Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB) is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME) for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR), and distinct mechanism(s) that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may improve targeted drug delivery. PMID- 27275868 TI - Effectiveness of a Rapid Lumbar Spine MRI Protocol Using 3D T2-Weighted SPACE Imaging Versus a Standard Protocol for Evaluation of Degenerative Changes of the Lumbar Spine. AB - OBJECTIVE: Reducing lumbar spine MRI scanning time while retaining diagnostic accuracy can benefit patients and reduce health care costs. This study compares the effectiveness of a rapid lumbar MRI protocol using 3D T2-weighted sampling perfection with application-optimized contrast with different flip-angle evolutions (SPACE) sequences with a standard MRI protocol for evaluation of lumbar spondylosis. MATERIALS AND METHODS: Two hundred fifty consecutive unenhanced lumbar MRI examinations performed at 1.5 T were retrospectively reviewed. Full, rapid, and complete versions of each examination were interpreted for spondylotic changes at each lumbar level, including herniations and neural compromise. The full examination consisted of sagittal T1-weighted, T2-weighted turbo spin-echo (TSE), and STIR sequences; and axial T1- and T2-weighted TSE sequences (time, 18 minutes 40 seconds). The rapid examination consisted of sagittal T1- and T2-weighted SPACE sequences, with axial SPACE reformations (time, 8 minutes 46 seconds). The complete examination consisted of the full examination plus the T2-weighted SPACE sequence. Sensitivities and specificities of the full and rapid examinations were calculated using the complete study as the reference standard. RESULTS: The rapid and full studies had sensitivities of 76.0% and 69.3%, with specificities of 97.2% and 97.9%, respectively, for all degenerative processes. Rapid and full sensitivities were 68.7% and 66.3% for disk herniation, 85.2% and 81.5% for canal compromise, 82.9% and 69.1% for lateral recess compromise, and 76.9% and 69.7% for foraminal compromise, respectively. CONCLUSION: Isotropic SPACE T2-weighted imaging provides high quality imaging of lumbar spondylosis, with multiplanar reformatting capability. Our SPACE-based rapid protocol had sensitivities and specificities for herniations and neural compromise comparable to those of the protocol without SPACE. This protocol fits within a 15-minute slot, potentially reducing costs and discomfort for a large subgroup of patients. PMID- 27275869 TI - Transition Metal Free Intermolecular Direct Oxidative C-N Bond Formation to Polysubstituted Pyrimidines Using Molecular Oxygen as the Sole Oxidant. AB - Various polysubstituted pyrimidines are smoothly formed via a base-promoted intermolecular oxidation C-N bond formation of allylic C(sp(3))-H and vinylic C(sp(2))-H of allyllic compounds with amidines using O2 as the sole oxidant. This protocol features protecting group free nitrogen sources, good functional group tolerance, high atom economy, and environmental advantages. PMID- 27275871 TI - If nursing associates are here to stay, get involved. AB - Like the idea or not - and professional opinion appears to be divided - nursing associates are coming. It was announced last week that about 1,000 students will be enrolled on courses next year, before starting work at a selection of test sites that are yet to be identified. PMID- 27275870 TI - Prevalence of Smokeless Tobacco among Low Socioeconomic Populations: A Cross Sectional Analysis. AB - BACKGROUND: Cost, social acceptability and non-stringent regulations pertaining to smokeless tobacco (SLT) product sales have made people choose and continue using SLT. If disaggregated data on smokeless forms and smoked practices of tobacco are reviewed, the incidence of SLT remains static. There is a strong positive correlation of SLT intake with the occurrence of adverse cardiovascular disease, particularly in the low socioeconomic populations. AIMS: To investigate the prevalence of smokeless tobacco, its initiation influence and risk factors associated with the practice among lower socioeconomic populations of Bangladesh. In this study, we explore the utilization of SLT among lower socioeconomic populations in industrialized zone of Bangladesh. METHODS: A cross-sectional analysis using both quantitative and categorical approaches was employed. Using systematic random sampling method, four focus group discussions (FGDs) were conducted and 459 participants were interviewed. Multiple logistic regression model was applied to distinguish the significant factors among the SLT users. RESULTS: Almost fifty percent of the respondents initiated SLT usage at the age of 15-24 years and another 22 percent respondents were smoking and using SLT concurrently. The bulk of the women respondents used SLT during their pregnancy. Nearly twenty five percent of the respondents tried to quit the practice of SLT and one-quarter had a plan to quit SLT in the future. More than twenty percent respondents were suffering from dental decay. A noteworthy correlation was found by gender (p<0.01), sufferings from SLT related disease (p<0.05). The multiple logistic regression analysis suggested that, males were 2.7 times more knowledgeable than that of females (p<0.01) about the adversative health condition of SLT usage. The respondents suffering from SLT related diseases were 3.7 times as more knowledgeable about the effect of the practice of SLT than the respondents without diseases (p<0.01). Regarding the knowledge about the health consequences of the practice of SLT, one participant in the FGD session commented that "although the mouth is the gateway to health, we infected our mouth by using Zarda and Gul". Again, informants opined that peer, family, curiosity and hospitality, culture are influencing factors for SLT initiation. CONCLUSION: counselling on tobacco, including SLT, health hazards have to be emphasized through mass media and it is essential for development of relevant policies and communication messages to make people aware of serious health consequences of SLT usages. PMID- 27275872 TI - Associate role in motion, despite concern over 'nursing on the cheap'. AB - Progress towards creating 1,000 nursing associates by 2017 has gathered pace. PMID- 27275873 TI - Belfast gives nurses freedom of the city for work during the Troubles. AB - All nurses who have worked or studied in Belfast were granted freedom of the city at a ceremony attended by about 300 representatives of the profession. PMID- 27275875 TI - Labour: we'll fight the plan. AB - The Labour party has pledged to fight the government every step of the way over the scrapping of nursing student bursaries, shadow health secretary Heidi Alexander said last week. PMID- 27275874 TI - Loss of bursary 'will lead to staff cuts and debts'. AB - Government plans to scrap the bursary for nursing, midwifery and other health students could cost the NHS 2,000 recruits a year, a new report warns. PMID- 27275876 TI - Nurses need to be leaders, NMC told. AB - Future nurses should be equipped to be experts in the fundamentals of nursing care while also demonstrating leadership skills, the Nursing and Midwifery Council has been told. PMID- 27275878 TI - 'We couldn't do this without the bursary'. AB - Our reporter Hannah Flynn sought out nurses' views at the 'save the bursary' lobby in London last week.... PMID- 27275877 TI - Report calls for nurses to have a greater role on governing bodies. AB - Nurses need to be seen as more than 'tokenistic' members of clinical commissioning group governing bodies, the RCN said. PMID- 27275880 TI - 'Patients with lung conditions should have specialist support'. AB - Patients with lung disease must have a nurse specialist to support them, the British Lung Foundation says. PMID- 27275881 TI - Be alert to suicide's silent risk factors. AB - An apparent absence of suicidal ideas cannot be assumed to show lack of risk, say researchers. PMID- 27275882 TI - Hospital staff 'frustrated' at lack of progress on delayed discharge. AB - Leading nurses have expressed their frustration at the latest figures revealing the scale of delays in discharging older people from hospital. PMID- 27275883 TI - Roald Dahl nurses' rose is a peach. AB - A nurse working for Roald Dahl's Marvellous Children's Charity launched a new rose at Chelsea Flower Show to raise money and mark Dahl's centenary. PMID- 27275884 TI - Effective, safe and affordable - the nurse's dream shopping list. AB - A team of nurses is being charged with the task of assessing equipment for cost and clinical effectiveness in a bid to improve NHS procurement. PMID- 27275885 TI - Changes in alcohol intake over time found to affect disease risk. AB - Post-menopausal woman who drank two extra alcoholic drinks a day over a five-year period increased their risk of breast cancer, but reduced their chance of developing coronary heart disease, a new study suggests. PMID- 27275886 TI - NHS should carry out more gastric band surgery to help fight obesity and diabetes. AB - The NHS has been urged to increase the numbers of patients receiving weight loss surgery to 50,000 a year, closer to the European average, to boost health and cut costs. PMID- 27275887 TI - Morning sickness drug is not linked to increased risk of birth defects. AB - A new study has found no evidence of a link between anti-nausea drug Zofran, also known as ondansetron, to an increased risk of having a child with birth defects. PMID- 27275888 TI - Lack of compliance with NICE guidance cited for variations in hip fracture surgery. AB - The use of hip fracture surgery varies widely across England, Wales and Northern Ireland, with men and people with high levels of socio-economic deprivation less likely to receive it. PMID- 27275889 TI - Breast cancer radiotherapy treatments calculated to have environmental impact. AB - Giving radiotherapy during surgery to early-stage breast cancer patients could save millions of travel miles and carbon dioxide emissions, according to a study. PMID- 27275890 TI - Prostate cancer. AB - Essential facts Prostate cancer starts in the prostate gland, at the base of the bladder in men. It surrounds the first part of the urethra, which carries urine from the bladder. The prostate gland helps in the production of semen, which is also carried in the urethra. It is the most common cancer in men - one in eight will develop it during their lifetime. PMID- 27275891 TI - Autism services 'let people down'. PMID- 27275892 TI - New funding cap for cancer drugs. PMID- 27275894 TI - Hard to define. AB - 'What I do,' said an artist friend, 'is walk away from my picture for a while, then come back and turn it sideways and upside down. Then I get a different perspective.' PMID- 27275893 TI - Making health a community issue. PMID- 27275895 TI - Let's hear it for loans. AB - Nursing bursaries. If we always do what we've always done, we'll always get what we've always got. PMID- 27275897 TI - Only skin deep. AB - It is the moment I have been dreading. Janet stares at my face and points to my nose. 'I think you'd better get that checked out,' she says. PMID- 27275896 TI - Voices - Jane Cummings believes her new strategy will help nurses lead NHS change. AB - After an extensive engagement process, last month I launched the new national framework for nursing, midwifery and care staff. PMID- 27275898 TI - Readers panel - When the pressure piles up. AB - Our experts consider a hot topic of the day. PMID- 27275899 TI - Medicine management. AB - I have a patient who would benefit from a medicine not available on the NHS. Is there any advice I can give? PMID- 27275904 TI - The best of the week's health-related TV and radio. AB - Our roundup of what's on. PMID- 27275900 TI - Starting out - Do not write off a placement before you've given it a chance. AB - Never dismiss a placement or take it for granted. We all hear stories about the ones we would not want to do at any cost. I've been there. PMID- 27275905 TI - Forest: Stay Focused app. AB - Did you know one sixth of smartphone owners check their mobiles 50 times a day? The Forest app is clearly aimed at those types of people. PMID- 27275906 TI - Ageist comments by colleagues need to be challenged. AB - I was horrified to read about a senior nurse leaving because of colleagues' unkind ageist comments in 'Age discrimination by fellow nurses is forcing me to leave' (letters, April 27). PMID- 27275907 TI - Action will boost awareness and training on domestic abuse. AB - Valid points on the need for nursing students to be able to competently detect and assess victims of intimate partner violence were made in Artur Dalfo Pibernat's letter in May's issue of Emergency Nurse magazine. PMID- 27275908 TI - This civic honour is just the boost our humble nursing spirits need. AB - For the nurses of Belfast, May 25 marked a special occasion as Belfast City Council conferred the Freedom of the City award to the RCN and Belfast nurses. PMID- 27275910 TI - Former director of RCN Wales Liz Hewett began at Ty Maeth in 1998. AB - Great story in Nursing Standard about the book Nursing Matters, which delves into the 50th anniversary of the RCN headquarters in Wales, Ty Maeth (features, May 18). However, Liz Hewett began working at the RCN in Wales in 1998 - not in 1988 as stated in the article. PMID- 27275911 TI - Join us on streets to demand our say in decisions on NHS reforms. AB - The government knows we have an NHS staffing shortage - that is something we can all agree on. It is also their selling point for the removal of NHS bursaries. If we introduce a loan system, they say, it will give us an additional 10,000 training places for nurses, midwives and allied health professionals. PMID- 27275913 TI - How to perform digital removal of faeces. AB - Rationale and key points This article provides practitioners with information about how to perform digital removal of faeces in a safe, effective and patient centred manner, promoting privacy and dignity. Passing faecal matter is essential to enable the elimination of waste. For some people, however, defecation is not possible without some form of intervention; this could be the administration of oral medication or an enema, insertion of suppositories or digital removal of faeces. ? Bowel care is a fundamental aspect of patient care. ? Digital removal of faeces should be performed by a practitioner competent in this skill. ? Digital removal of faeces is an invasive procedure and should only be carried out when necessary following holistic patient assessment. Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How you think this article will improve your practice. 2. How the patient receiving the care you delivered might have felt. Subscribers can upload their reflective accounts at: rcni.com/portfolio . PMID- 27275912 TI - Health visitors know the benefits of breastfeeding. AB - I find it astonishing that the article promoting health visiting (careers, May 4) should portray formula feeding as normal in its accompanying photograph. This undermines the individual woman's choice to breastfeed. It also reinforces the societal norm of formula feeding. PMID- 27275914 TI - The effect of nursing staff on student learning in the clinical setting. AB - Aim To explore baccalaureate nursing students' perspectives of the influence of nursing staff on their learning and experience in the clinical setting. Method A qualitative description approach was used. Thirty nursing students were interviewed individually or in focus groups. Data were analysed using content analysis. Four researchers analysed the data separately and agreed on the themes. Findings Nursing staff had positive (enabling) and negative (hindering) effects on students' clinical learning and socialisation to nursing. Nursing staff may encourage and excite students when they behave as positive mentors, facilitators and motivators. However, their actions may also have a negative effect on students, decreasing their confidence, learning and desire to continue in the profession. Conclusion Nursing staff influence student learning. Their actions, attitude and willingness to teach are influential factors. The findings have implications for patient safety, nurse retention and recruitment, and preparing students for professional practice. PMID- 27275915 TI - Moving and handling: reducing risk through assessment. AB - Manual handling injuries can occur almost anywhere in a healthcare environment, and most staff perform a variety of moving and handling tasks every day. Heavy lifting, awkward posture, and previous or existing injury can increase the risk of musculoskeletal disorders. A healthcare professional's involvement in moving and handling is more widespread than it might appear, and their actions and understanding of techniques, legislation and guidelines have a direct effect on patient care. Every situation that involves the handling, or partial handling, of a person presents varying levels of risk to the patient and the carer. Maintaining a good level of patient mobility and independence is an essential part of care delivery and can reduce the risk of long-term physical and psychological effects. Delivery of care should focus on the individual's capacity, not their incapacity, to ensure that they are treated with dignity and respect. PMID- 27275916 TI - Pulmonary oedema. AB - This informative CPD article on acute pulmonary oedema has improved my knowledge of the condition. PMID- 27275917 TI - Be a leading candidate. AB - Nerves can take hold and speech become garbled when you are put on the spot. Here, we offer expert advice on being the best you can be at a job interview. PMID- 27275919 TI - Dual role in mesothelioma care. AB - Mention the word mesothelioma and many nurses will know of someone whose life has been affected by this increasingly common cancer. PMID- 27275920 TI - Student life - Professional conduct. AB - It is often said that we form assumptions of people within a few minutes of meeting. PMID- 27275921 TI - Catalase-Loaded TaOx Nanoshells as Bio-Nanoreactors Combining High-Z Element and Enzyme Delivery for Enhancing Radiotherapy. AB - A novel type of bio-nanoreactor with catalase loaded inside TaOx hollow nanoshells is fabricated via a mild one-step method. Such bio-nanoreactors could efficiently improve the tumor oxygenation by supplying oxygen via decomposition of endogenic H2 O2 in a tumor microenvironment, and thus synergistically enhance the efficacy of cancer radiotherapy by both depositing radiation energy within the tumor and overcoming hypoxia-induced radiotherapy resistance. PMID- 27275922 TI - Unilateral Gottron Papules in a Patient Following a Stroke: Clinical Insights Into the Disease Mechanisms and Pathophysiology of Cutaneous Dermatomyositis. PMID- 27275923 TI - Topical Delivery of Tenofovir Disoproxil Fumarate and Emtricitabine from Pod Intravaginal Rings Protects Macaques from Multiple SHIV Exposures. AB - Topical preexposure prophylaxis (PrEP) against HIV has been marginally successful in recent clinical trials with low adherence rates being a primary factor for failure. Controlled, sustained release of antiretroviral (ARV) drugs may help overcome these low adherence rates if the product is protective for extended periods of time. The oral combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is currently the only FDA-approved ARV drug for HIV PrEP. A novel pod-intravaginal ring (IVR) delivering TDF and FTC at independently controlled rates was evaluated for efficacy at preventing SHIV162p3 infection in a rigorous, repeat low-dose vaginal exposure model using normally cycling female pigtailed macaques. Six macaques received pod-IVRs containing TDF (65 mg) and FTC (68 mg) every two weeks, and weekly vaginal exposures to 50 TCID50 of SHIV162p3 began one week after the first pod-IVR insertion. All pod-IVR-treated macaques were fully protected throughout the study (P = 0.0002, Log-rank test), whereas all control animals became infected with a median of 4 exposures to infection. The topical, sustained release of TDF and FTC from the pod-IVR maintained protective drug levels in macaques over four months of virus exposures. This novel and versatile delivery system has the capacity to deliver and maintain protective levels of multiple drugs and the protection observed here warrants clinical evaluation of this pod-IVR design. PMID- 27275924 TI - The Protein Kinase CK2 Mediates Cross-Talk between Auxin- and Salicylic Acid Signaling Pathways in the Regulation of PINOID Transcription. AB - The protein kinase CK2 is a ubiquitous and highly conserved enzyme, the activity of which is vital for eukaryotic cells. We recently demonstrated that CK2 modulates salicylic acid (SA) homeostasis in Arabidopsis thaliana, and that functional interplay between CK2 and SA sustains transcriptional expression of PIN-FORMED (PIN) genes. In this work, we show that CK2 also plays a key role in the transcriptional regulation of PINOID (PID), an AGC protein kinase that modulates the apical/basal localization of auxin-efflux transporters. We show that PID transcription is up-regulated by auxin and by SA and that CK2 is involved in both pathways. On the one hand, CK2 activity is required for proteosome-dependent degradation of AXR3, a member of the AUX/IAA family of auxin transcriptional repressors that must be degraded to activate auxin-responsive gene expression. On the other hand, the role of CK2 in SA homeostasis and, indirectly, in SA-driven PID transcription, was confirmed by using Arabidopsis NahG transgenic plants, which cannot accumulate SA. In conclusion, our results evidence a role for CK2 as a functional link in the negative cross-talk between auxin- and SA-signaling. PMID- 27275925 TI - Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome. AB - BACKGROUND: Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKalpha, IkB, P38, five cytokines IL-6, IL8, IL-1beta, IL-18, and MIP-1beta. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. CONCLUSIONS/SIGNIFICANCE: Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS progression. PMID- 27275926 TI - Novel Dielectric Coagulometer Identifies Hypercoagulability in Patients with a High CHADS2 Score without Atrial Fibrillation. AB - BACKGROUND: Recent reports showed that the CHADS2 score predicted the risk of strokes in patients without atrial fibrillation (AF). Although the hypercoagulability may contribute to the thrombogenesis, it has not been fully investigated due to a lack of a sensitive evaluation modality. Recently a novel dielectric blood coagulometry (DBCM) was invented for evaluating the coagulability by measuring the temporal change in whole blood dielectric permittivity. OBJECTIVE: We evaluated the utility of the DBCM for identifying the coagulability. PATIENTS/METHODS: For fundamental experiments, 133 citrated blood samples were drawn from subjects with or without heparin administration. A DBCM analysis was performed to find the adequate coagulation index, and to delineate its measurement range by adding recombinant human tissue factor (TF) or heparin. Then the coagulability was assessed by DBCM and conventional coagulation assays in 84 subjects without AF, who were divided into 3 groups by their CHADS2 score. Another 17 patients who received warfarin were also assessed by DBCM to evaluate the effect of anticoagulants. RESULTS AND CONCLUSIONS: We calculated the derivative of the dielectric permittivity change after recalcification, and extracted the end of acceleration time (EAT) as a novel index. The EAT showed a dose-dependent shortening with the addition of serial dilutions of TF (*10-2 to *10-4), and a dose-dependent prolongation with the addition of heparin (0.05 to 0.15 U/ml). The EAT was significantly shorter in the higher CHADS2 score group (19.8 +/- 4.8, 18.6 +/- 3.1, and 16.3 +/- 2.7 min in the CHADS2 = 0, 1, and >=2 groups, respectively, p = 0.0065 by ANOVA). Patients receiving warfarin had a significantly more prolonged EAT than those without warfarin (18.6+/-4.2 vs. 25.8+/-7.3 min, p <0.001). DBCM detected the whole blood coagulability with a high sensitivity. Subjects with higher CHADS2 scores exhibited hypercoagulability without AF. PMID- 27275927 TI - Congenital Lobar Emphysema in an Adult. PMID- 27275928 TI - A Critical Evaluation of the Down Syndrome Diagnosis for LB1, Type Specimen of Homo floresiensis. AB - The Liang Bua hominins from Flores, Indonesia, have been the subject of intense scrutiny and debate since their initial description and classification in 2004. These remains have been assigned to a new species, Homo floresiensis, with the partial skeleton LB1 as the type specimen. The Liang Bua hominins are notable for their short stature, small endocranial volume, and many features that appear phylogenetically primitive relative to modern humans, despite their late Pleistocene age. Recently, some workers suggested that the remains represent members of a small-bodied island population of modern Austro-Melanesian humans, with LB1 exhibiting clinical signs of Down syndrome. Many classic Down syndrome signs are soft tissue features that could not be assessed in skeletal remains. Moreover, a definitive diagnosis of Down syndrome can only be made by genetic analysis as the phenotypes associated with Down syndrome are variable. Most features that contribute to the Down syndrome phenotype are not restricted to Down syndrome but are seen in other chromosomal disorders and in the general population. Nevertheless, we re-evaluated the presence of those phenotypic features used to support this classification by comparing LB1 to samples of modern humans diagnosed with Down syndrome and euploid modern humans using comparative morphometric analyses. We present new data regarding neurocranial, brain, and symphyseal shape in Down syndrome, additional estimates of stature for LB1, and analyses of inter- and intralimb proportions. The presence of cranial sinuses is addressed using CT images of LB1. We found minimal congruence between the LB1 phenotype and clinical descriptions of Down syndrome. We present important differences between the phenotypes of LB1 and individuals with Down syndrome, and quantitative data that characterize LB1 as an outlier compared with Down syndrome and non-Down syndrome groups. Homo floresiensis remains a phenotypically unique, valid species with its roots in Plio-Pleistocene Homo taxa. PMID- 27275929 TI - Nanoparticulate Mineralized Collagen Scaffolds and BMP-9 Induce a Long-Term Bone Cartilage Construct in Human Mesenchymal Stem Cells. AB - Engineering the osteochondral junction requires fabrication of a microenvironment that supports both osteogenesis and chondrogenesis. Multiphasic scaffold strategies utilizing a combination of soluble factors and extracellular matrix components are ideally suited for such applications. In this work, the contribution of an osteogenic nanoparticulate mineralized glycosaminoglycan scaffold (MC-GAG) and a dually chondrogenic and osteogenic growth factor, BMP-9, in the differentiation of primary human mesenchymal stem cells (hMSCs) is evaluated. Although 2D cultures demonstrate alkaline phosphatase activity and mineralization of hMSCs induced by BMP-9, MC-GAG scaffolds do not demonstrate significant differences in the collagen I expression, osteopontin expression, or mineralization. Instead, BMP-9 increases expression of collagen II, Sox9, aggrecan (ACAN), and cartilage oligomeric protein. However, the hypertrophic chondrocyte marker, collagen X, is not elevated with BMP-9 treatment. In addition, histologic analyses demonstrate that while BMP-9 does not increase mineralization, BMP-9 treatment results in an increase of sulfated glycosaminoglycans. Thus, the combination of BMP-9 and MC-GAG stimulates chondrocytic and osteogenic differentiation of hMSCs. PMID- 27275930 TI - SIRT1 prevents pulmonary thrombus formation induced by arachidonic acid via downregulation of PAF receptor expression in platelets. AB - SIRT1, a class III histone deacetylase, is critically involved in cellular response to stress and modulates cardiovascular risk factors. However, its role in thrombus formation is largely unknown. Thus, this study investigated the effect of SIRT1 on pulmonary thrombus formation, and then identified its role in the modulation of platelet aggregation. In isolated human platelets, cell aggregation was increased by various platelet activators, such as platelet activating factor (PAF), arachidonic acid (AA), ADP, and thrombin. AA- and PAF mediated platelet aggregations were suppressed by WEB2086, a PAF receptor (PAFR) antagonist. Pulmonary thrombus formation induced by PAF or AA was also attenuated by WEB2086, suggesting that PAFR plays a key role in AA-induced platelet aggregation. In platelets isolated from SIRT1-TG mice as well as in platelets treated with resveratrol or reSIRT1, PAFR expression was decreased, whereas this expressional downregulation by SIRT1 activators was inhibited in platelets treated with MG132 (a proteasome inhibitor) or NH4Cl (a lysosome inhibitor). Furthermore, platelet aggregation induced by AA was markedly attenuated by resveratrol and reSIRT1. Likewise, the increased pulmonary thrombus formation in mice treated with AA was also attenuated by SIRT1 activators. In line with these results, pulmonary thrombus formation was markedly attenuated in SIRT1-TG mice. Taken together, this study showed that SIRT1 downregulates PAFR expression on platelets via proteasomal and lysosomal pathways, and that this downregulation inhibits platelet aggregation in vitro and pulmonary thrombus formation in vivo. PMID- 27275931 TI - Unlikely Fluctuations and Non-Equilibrium Work Theorems-A Simple Example. AB - An exciting development in statistical mechanics has been the elucidation of a series of surprising equalities involving the work done during a nonequilibrium process. Astumian has presented an elegant example of such an equality, involving a colloidal particle undergoing Brownian motion in the presence of gravity. We analyze this example; its simplicity, and its link to geometric Brownian motion, allows us to clarify the inner workings of the equality. Our analysis explicitly shows the important role played by large, unlikely fluctuations. PMID- 27275932 TI - Correlation of In Vivo and In Vitro Assay Results for Assessment of Free Radical Scavenging Activity of Green Tea Nutraceuticals. AB - Green tea (GT)-derived catechins; epigallocatechin gallate (EGCG) in particular are commonly used nutraceuticals for their free-radical scavenging activity (FRSA). The influence of photodegradation on the protective power of GT nutracenticals against oxidative stress was thoroughly explored. Photodegradation of GT extracts was carried out and monitored using orthogonal stability indicating testing protocol; in vitro and in vivo assays. Total polyphenol content (TPC) and FRSA were determined spectrophotometrically while EGCG was selectively monitored using SPE-HPLC. In vivo assessment of photodegraded samples was investigated via measuring a number of biomarkers for hepatic oxidative stress and apoptosis (caspase-3, inducible nitric oxide synthase, nitric oxide, mitogen-activated protein kinase, glutathione, thiobarbituric acid reactive substances, nuclear factor kappa beta, and nuclear factor erythroid 2-related factor) as well as liver damage (alanine transaminase and aspartate transaminase) in serum of rats previously subjected to oxidative stress. Results showed complete degradation of EGCG in photodegraded green tea samples with no correlation with either TPC or FRSA. On the other hand, in vivo assay results revealed not only loss of activity but formation of harmful pro-oxidants. Photostability was found crucial for the protective effect of GT extract against lead acetate insult. Results confirmed that careful design of quality control protocols requires correlation of chemical assays to bioassays to verify efficacy, stability, and most importantly safety of nutraceuticals. PMID- 27275933 TI - Improving your care of patients with spinal cord injury/disease. AB - Ninety percent of patients with spinal cord injury/disease identify FPs as their "regular doctors." So what can you do to keep them healthy and out of the hospital? PMID- 27275934 TI - Diabetes update: Your guide to the latest ADA standards. AB - The authors highlight the latest changes in the ADA standards and review recommendations of particular relevance for family physicians. PMID- 27275935 TI - Is platelet-rich plasma right for your patient? AB - Many pro athletes claim that platelet-rich plasma has improved their performance and saved their careers. But is it right for your patients? And if so, which ones? PMID- 27275936 TI - Increased syncopal episodes post surgery . Dx? AB - This case demonstrates that non-massive PE can present as vasovagal syncope. Recognizing that PE could lead to reflex-mediated syncope in the absence of massive emboli, it is important to rule it out in the evaluation of patients with vasovagal syncope when risk factors for PE are present. PMID- 27275937 TI - 8 USPSTF recommendations FPs need to know about. AB - Treat high blood pressure only if measurements taken outside of the office confirm an initial high BP reading . Screen blood-glucose levels in overweight/obese individuals 40 to 70 years old . and more. PMID- 27275939 TI - Elderly woman with sharp shoulder pain. AB - The patient denied recent trauma or any heavy lifting, but she'd lost 10 pounds over the previous month. What was causing her shoulder pain? PMID- 27275938 TI - PURLs: "Go low" or say "No" to aggressive systolic BP goals? AB - The SPRINT trial demonstrated the benefits--and risks--of reaching a systolic target <120 mm Hg in non-diabetic patients at high risk for CV events. Here's who might benefit. PMID- 27275940 TI - Help Desk Answers: Do corticosteroids reduce bronchiolitis hospitalizations? AB - Corticosteroids alone don't decrease hospital admissions or length of stay among children with bronchiolitis. Combining oral dexamethasone and inhaled epinephrine appears to prevent one hospital admission for every 11 patients treated. PMID- 27275941 TI - A valuable string of PURLs. AB - To qualify as a PURL, a study had to meet 6 criteria. It had to be scientifically valid, relevant to family medicine, applicable in a medical care setting, immediately implementable, clinically meaningful, and practice changing. These criteria still stand today. PMID- 27275942 TI - Clinical Inquiry: Which nonhormonal treatments are effective for hot flashes? AB - Selective serotonin reuptake inhibitors (SSRIs [fluoxetine, sertraline, paroxetine]) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine, as well as clonidine and gabapentin, reduce hot flashes by about 25% (approximately one per day) in women with and without a history of breast cancer. No studies compare medications against each other to determine a single best option. PMID- 27275943 TI - Painful, swollen, oozing right great toe. AB - We initially suspected septic arthritis or osteomyelitis in this patient. Further investigation proved it was neither. PMID- 27275945 TI - Differences in Pediatric Pain Management by Unit Types. AB - PURPOSE: The purpose of this study was to determine differences in pediatric pain management by unit type in hospitals across the United States. The aims were to (a) compare unit-type rates of assessment, intervention, and reassessment (AIR), and (b) describe differences in assessment tools and intervention use by unit type. DESIGN: The study used a cross-sectional design. A secondary analysis of 2013 data from the National Database of Nursing Quality Indicators (NDNQI(r)) pain AIR cycle indicator was conducted. The sample included 984 pediatric units in 390 hospitals. METHODS: Data were gathered via retrospective chart review on the pain assessment tool used, presence of pain, interventions, and reassessment. Descriptive statistics and the Kruskal-Wallis one-way analysis of variance test were conducted. Post-hoc analyses included the Wilcoxon-rank sum test with Bonferroni correction. FINDINGS: Across all units the mean unit-level percentage of patients assessed for pain was 99.6%. Of those patients assessed, surgical units had the highest average unit-level percentage of patients with pain, while Level 4 neonatal intensive care units (NICUs) had the lowest. The most commonly used assessment tool among all units was the Faces, Legs, Activity, Crying, and Consolability (FLACC) Scale. The Neonatal Pain, Agitation, and Sedation Scale (N PASS) and Neonatal Infant Pain Scale (NIPS) specifically developed for infants were more commonly used across NICU unit types. The mean unit-level percentage of patients with pain receiving an intervention was 89.4%, and reassessment was 83.6%. Overall, pharmacologic methods were the most common pain intervention, while music was the least common. CONCLUSIONS: Assessments were performed routinely, yet interventions and reassessments were not. Pain AIR cycle completion varied by unit type. Pain was also widely present across many unit types, and pharmacologic methods were most frequently used. CLINICAL RELEVANCE: Frontline nurses are instrumental to pain management and have the ability to improve patient care and outcomes by effectively managing pain. A comprehensive understanding of it provides valuable insight into improving our practice to produce the best outcomes for pediatric patients. PMID- 27275944 TI - Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits. AB - INTRODUCTION: In bone and joint infections (BJIs), bacterial toxins are major virulence factors: Panton-Valentine leukocidin (PVL) expression leads to severe local damage, including bone distortion and abscesses, while alpha-hemolysin (Hla) production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs) expressed by community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 (LAC WT) were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated. MATERIALS AND METHODS: We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic Deltapsm derivatives (LAC Deltapsmalpha and LAC Deltapsmalphabetahld) using an inoculum of 3 * 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney), lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D) 14). RESULTS: Severe sepsis-related mortality tended to be lower for Deltapsm derivatives (Kaplan-Meier curves, P = .06). Non survivors' bone LAC-Deltapsmalpha (6.9 log10 CFUs/g of bone, P = .04) or Deltapsmalphabetahld (6.86 log10 CFUs/g of bone, P = .014) densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone). Conversely, lung Deltapsmalphabetahld CFUs were significantly lower than LAC WT (P = .04). LAC Deltapsmalpha, Deltapsmalphabetahld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone). Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC Deltapsmalpha- and Deltapsmalphabetahld-infected rabbits compared to LAC WT (P = .04 and .01, respectively) but with comparable lung bacterial densities. CONCLUSION: Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early phase of infection, but did not affect local severity of USA300 rabbit osteomyelitis. PMID- 27275946 TI - Discovery of the Potent and Selective M1 PAM-Agonist N-[(3R,4S)-3 Hydroxytetrahydro-2H-pyran-4-yl]-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]pyridine 2-carboxamide (PF-06767832): Evaluation of Efficacy and Cholinergic Side Effects. AB - It is hypothesized that selective muscarinic M1 subtype activation could be a strategy to provide cognitive benefits to schizophrenia and Alzheimer's disease patients while minimizing the cholinergic side effects observed with nonselective muscarinic orthosteric agonists. Selective activation of M1 with a positive allosteric modulator (PAM) has emerged as a new approach to achieve selective M1 activation. This manuscript describes the development of a series of M1-selective pyridone and pyridine amides and their key pharmacophores. Compound 38 (PF 06767832) is a high quality M1 selective PAM that has well-aligned physicochemical properties, good brain penetration and pharmacokinetic properties. Extensive safety profiling suggested that despite being devoid of mAChR M2/M3 subtype activity, compound 38 still carries gastrointestinal and cardiovascular side effects. These data provide strong evidence that M1 activation contributes to the cholinergic liabilities that were previously attributed to activation of the M2 and M3 receptors. PMID- 27275947 TI - Cancer Appetite and Symptom Questionnaire (CASQ) for Brazilian Patients: Cross Cultural Adaptation and Validation Study. AB - BACKGROUND: Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. METHODS: This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (chi2/df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach's alpha coefficient (alpha), and the invariance of the model in independent samples was estimated by a multigroup analysis (Deltachi2). RESULTS: Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (chi2/df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). The model exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 alpha = .82). The refined model showed strong invariance in two independent samples (Deltachi2: lambda: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Deltachi2: lambda: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Deltachi2: lambda: p = .058; i: p < .001; Res: p < .001). CONCLUSION: The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatments. PMID- 27275948 TI - Why Patients Delay Their First Contact with Health Services After Stroke? A Qualitative Focus Group-Based Study. AB - BACKGROUND: Despite national and local French information campaigns, when acute stroke occurs, waiting times before calling mobile emergency medical services (EMS) to receive appropriate treatment (i.e. thrombolysis) and decrease the risk of physical disability, remain long. We aimed to identify the representations of stroke in the general population and to determine barriers to and facilitators for rapidly contacting EMS. METHOD: We conducted a qualitative study among the general population with 10 focus groups, 5 comprising employed people (N = 29) and 5 comprising retirees (N = 32). The themes discussed were general knowledge about stroke and its risk factors, symptoms, appropriate management and the awareness that stroke is an emergency issue. RESULTS: In addition to a lack of knowledge about stroke, other barriers to rapidly contacting the EMS were difficulties in recognizing symptoms and understanding that these symptoms constitute an emergency. Furthermore, when faced with stroke, a feeling of inevitability and fatalism about the consequences of a stroke was highlighted. Participants were unaware of the existence of an effective treatment and they mistrusted medical competences. Finally, we found a strong presence and participant appreciation of common knowledge, resulting in the sharing of experiences of stroke. This could partly compensate for the lack of specific knowledge about symptom recognition and appropriate action. CONCLUSION: Information campaigns should not only inform the public about stroke symptoms in order to ensure people act appropriately, but should also focus on increasing public awareness about the fact that an effective treatment exists. PMID- 27275950 TI - Two-Dimensional Titanium Carbide MXene As a Cathode Material for Hybrid Magnesium/Lithium-Ion Batteries. AB - As an alternative to pure lithium-ion, Li+, systems, a hybrid magnesium, Mg2+, and Li+ battery can potentially combine the high capacity, high voltage, and fast Li+ intercalation of Li-ion battery cathodes and the high capacity, low cost, and dendrite-free Mg metal anodes. Herein, we report on the use of two-dimensional titanium carbide, Ti3C2Tx (MXene), as a cathode in hybrid Mg2+/Li+ batteries, coupled with a Mg metal anode. Free-standing and flexible Ti3C2Tx/carbon nanotube composite "paper" delivered ~100 mAh g-1 at 0.1 C and ~50 mAh g-1 at 10 C. At 1 C the capacity was maintained for >500 cycles at 80 mAh g-1. The Mo2CTx MXene also demonstrated good performance as a cathode material in this hybrid battery. Considering the variety of available MXenes, this work opens the door for exploring a new large family of 2D materials with high electrical conductivity and large intercalation capacity as cathodes for hybrid Mg2+/Li+ batteries. PMID- 27275949 TI - 207-nm UV Light-A Promising Tool for Safe Low-Cost Reduction of Surgical Site Infections. II: In-Vivo Safety Studies. AB - BACKGROUND: UVC light generated by conventional germicidal lamps is a well established anti-microbial modality, effective against both bacteria and viruses. However, it is a human health hazard, being both carcinogenic and cataractogenic. Earlier studies showed that single-wavelength far-UVC light (207 nm) generated by excimer lamps kills bacteria without apparent harm to human skin tissue in vitro. The biophysical explanation is that, due to its extremely short range in biological material, 207 nm UV light cannot penetrate the human stratum corneum (the outer dead-cell skin layer, thickness 5-20 MUm) nor even the cytoplasm of individual human cells. By contrast, 207 nm UV light can penetrate bacteria and viruses because these cells are physically much smaller. AIMS: To test the biophysically-based hypothesis that 207 nm UV light is not cytotoxic to exposed mammalian skin in vivo. METHODS: Hairless mice were exposed to a bactericidal UV fluence of 157 mJ/cm2 delivered by a filtered Kr-Br excimer lamp producing monoenergetic 207-nm UV light, or delivered by a conventional 254-nm UV germicidal lamp. Sham irradiations constituted the negative control. Eight relevant cellular and molecular damage endpoints including epidermal hyperplasia, pre-mutagenic UV-associated DNA lesions, skin inflammation, and normal cell proliferation and differentiation were evaluated in mice dorsal skin harvested 48 h after UV exposure. RESULTS: While conventional germicidal UV (254 nm) exposure produced significant effects for all the studied skin damage endpoints, the same fluence of 207 nm UV light produced results that were not statistically distinguishable from the zero exposure controls. CONCLUSIONS: As predicted by biophysical considerations and in agreement with earlier in vitro studies, 207-nm light does not appear to be significantly cytotoxic to mouse skin. These results suggest that excimer-based far-UVC light could potentially be used for its anti microbial properties, but without the associated hazards to skin of conventional germicidal UV lamps. PMID- 27275951 TI - Poly(1,3-propylene sebacate) and Poly(sebacoyl diglyceride): A Pair of Potential Polymers for the Proliferation and Differentiation of Retinal Progenitor Cells. AB - Using suitable polymers as a carrier for growing and delivering retinal progenitor cells (RPCs) is a promising therapeutic strategy in retinal cell replacement therapy. Herein recently developed polymer, poly(sebacoyl diglyceride) (PSeD), is selected and its nonhydroxylized counterpart poly(1,3 propylene sebacate) (PPS) is designed to evaluate their potentials for RPC growth and future RPC application. The structures and mechanical properties of the polymers are characterized. The cytocompatibility and effects of these polymers on RPC proliferation, differentiation, and migration are systematically investigated in vitro. Our data show that PPS and PSeD display excellent cytocompatibility with low expression of inflammation and apoptosis factors, which benefit RPC growth. In proliferation assays reveal that RPCs expands well on the polymers, but PPS performs the best for RPC expansion, indicating that PPS can remarkably promote RPC proliferation. In differentiation conditions, RPCs grown on PSeD are more likely to differentiate toward retinal neurons, including photoreceptors, the most interesting type of cells for retinal cell-replacement therapy. Additionally, our results demonstrate that RPCs grown on PSeD display an outstanding ability to migrate. In conclusion, PPS can markedly promote RPC proliferation, whereas PSeD can enhance RPC differentiation toward retinal neurons, suggesting that PSeD and PPS have potential applications in future retinal cell-replacement therapies. PMID- 27275952 TI - High sensitivity plasmonic biosensor based on nanoimprinted quasi 3D nanosquares for cell detection. AB - Quasi three-dimensional (3D) plasmonic nanostructures consisting of Au nanosquares on top of SU-8 nanopillars and Au nanoholes on the bottom were developed and fabricated using nanoimprint lithography with simultaneous thermal and UV exposure. These 3D plasmonic nanostructures were used to detect cell concentration of lung cancer A549 cells, retinal pigment epithelial (RPE) cells, and breast cancer MCF-7 cells. Nanoimprint technology has the advantage of producing high uniformity plasmonic nanostructures for such biosensors. Multiple resonance modes were observed in these quasi 3D plasmonic nanostructures. The hybrid coupling of localized surface plasmon resonances and Fabry-Perot cavity modes in the quasi 3D nanostructures resulted in high sensitivity of 496 nm/refractive index unit. The plasmonic resonance peak wavelength and sensitivity could be tuned by varying the Au thickness. Resonance peak shifts for different cells at the same concentration were distinct due to their different cell area and confluency. The cell concentration detection limit covered a large range of 5 * 10(2) to 1 * 10(7) cells ml(-1) with these new plasmonic nanostructures. They also provide a large resonance peak shift of 51 nm for as little as 0.08 cells mm(-2) of RPE cells for high sensitivity cell detection. PMID- 27275953 TI - The Association of Metabolic Syndrome with Diabetic Retinopathy: The Korean National Health and Nutrition Examination Survey 2008-2012. AB - AIMS: To explore gender differences and associations between metabolic syndrome (MetS) and its components, and diabetic retinopathy (DR) in Korean adults aged 40 years and older with diabetes. METHODS: We analyzed data from the Korean National Health and Nutrition Examination Surveys (2008-2012). In total, 2,576 type 2 diabetic participants, aged 40 and older, were evaluated. Seven standard retinal fundus photographs were obtained after pupil dilation in both eyes. DR was graded using the modified Airlie House classification system. Vision-threatening diabetic retinopathy (VTDR) included proliferative diabetic retinopathy and clinically significant macular edema. MetS was defined according to the Joint Interim Statement, proposed in 2009, by the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Multivariate logistic regression analysis was used to assess the relationship between MetS and its individual components with DR and VTDR. RESULTS: After controlling for confounders, MetS was not associated with DR in men or women. Moreover, the risk for DR or VTDR did not increase with increasing MetS components. However, high waist circumference was significantly inversely associated with VTDR (adjusted odds ratio = 0.36; 95% confidence interval = 0.14 0.93) only in men. CONCLUSIONS: MetS was not associated with DR or VTDR in a Korean diabetic population. However, among MetS components, it seems that abdominal obesity was inversely associated with VTDR in Korean diabetic men. PMID- 27275954 TI - Two-thirds of adolescents who received active perinatal care after extremely preterm birth had mild or no disabilities. AB - AIM: Active perinatal care (APC) increases the survival of extremely preterm (EPT) infants, but may increase the rate of disabilities. We examined neurodevelopmental outcomes in adolescents aged 10-15 years who were born EPT and received APC in two Swedish tertiary care centres. METHODS: Cognitive function was assessed using the Wechsler Intelligence Scale for Children, and neurosensory impairments were assessed by reviewing the case records and a standard parent health questionnaire. The outcomes were compared to term-born controls. RESULTS: We assessed 132 EPT adolescents and 103 controls. The rates of cerebral palsy, moderate to severe visual impairment and moderate to severe hearing impairment were 9%, 4% and 6%, respectively, for the EPT children and zero for the controls. Serious cognitive impairment was present in 31% of the EPT adolescents and 5% of the controls. Combining impairments across domains showed that 34% of EPT adolescents had moderate and severe disabilities compared with 5% of the controls. Impairments were more common at 23-24 weeks of gestational age (43%) than at 25 weeks (28.4%). CONCLUSION: Two-thirds (66%) of adolescents born EPT who received APC had mild or no disabilities. Our results are relevant for healthcare providers and clinicians counselling families. PMID- 27276000 TI - Donor/Acceptor-Stabilized 1-Silaketene: Reversible [2+2] Cycloaddition with Pyridine and Evolution by an Olefin Metathesis Reaction. AB - The reaction of silacyclopropylidene 1 with benzaldehyde generates a 1-silaketene complex 2 by a formal atomic silicon insertion into the C=O bond of the aldehyde. The highly reactive 1-silaketene 2 undergoes a reversible [2+2] cycloaddition with pyridine to give sila-beta-lactam 3. Of particular interest, in the presence of 4-dimethylaminopyridine (DMAP), 1-silaketene complex 2 evolves through an intramolecular olefin metathesis reaction, generating a new 1-silaketene complex 8 and cis-stilbene. Theoretical studies suggest that the reaction proceeds through the formation of a transient silacyclobutanone, a four-membered-ring intermediate, similar to that proposed by Chauvin and co-workers for the transition-metal-based olefin metathesis. PMID- 27276001 TI - Therapeutic Advances in Localized Pancreatic Cancer. AB - IMPORTANCE: It is estimated that pancreatic cancer (PC) will become the second leading cause of cancer-related death in the United States by 2030. OBSERVATIONS: Clinical and preclinical data support the understanding that PC metastases occur early in the pathogenesis of this disease, even before the primary tumor can be detected. This has important implications for the clinical management of patients with localized PC, as surgery alone is unlikely to be curative for most patients. The delivery of postoperative adjuvant therapy is problematic in this disease because of the magnitude of the operation needed to remove the primary tumor, which can affect patient recovery and delay (sometimes indefinitely) the delivery of systemic therapy. For these reasons, the use of chemotherapy and/or chemoradiation prior to surgery (neoadjuvant therapy) is increasingly recognized as the preferred strategy for treatment sequencing. Neoadjuvant therapy is recommended for patients with borderline resectable PC and, at some centers, neoadjuvant therapy has been extended to patients with resectable PC as well. Importantly, therapeutic advances in multidrug systemic therapy and radiation therapy have already been adopted in the neoadjuvant setting where treatment toxicity will not be compounded by surgical recovery. In addition, the use of local-regional therapies in highly selected patients with locally advanced PC, following a prolonged period of induction systemic therapy, will be an area of intense scrutiny. Future improvements in diagnostic biomarkers may allow for real time sequencing of multimodality therapy for individual patients based on a more accurate and timely assessment of treatment response. CONCLUSIONS AND RELEVANCE: Neoadjuvant treatment sequencing allows patients to receive multimodality therapy in a manner that prioritizes early exposure to systemic therapy to maximize the treatment of micrometastatic disease in an immune-competent host prior to surgical intervention. Patients who complete all intended neoadjuvant therapy, including surgery, experience an overall survival benefit that is unmatched by a surgery-first approach. PMID- 27276002 TI - Longitudinal Analysis of Gender Differences in Academic Productivity Among Medical Faculty Across 24 Medical Schools in the United States. AB - PURPOSE: To examine gender differences in academic productivity, as indicated by publications and federal grant funding acquisition, among a longitudinal cohort of medical faculty from 24 U.S. medical schools, 1995 to 2012-2013. METHOD: Data for this research were taken from the National Faculty Survey involving a survey with medical faculty recruited from medical schools in 1995, and followed up in 2012-2013. Data included surveys and publication and grant funding databases. Outcomes were number of publications, h-index, and principal investigator on a federal grant in the prior two years. Gender differences were assessed using negative binomial regression models for publication and h-index outcomes, and logistic regression for the grant funding outcome; analyses adjusted for race/ethnicity, rank, specialty area, and years since first academic appointment. RESULTS: Data were available for 1,244 of the 1,275 (98%) subjects eligible for the follow-up study. Men were significantly more likely than women to be married/partnered, have children, and hold the rank of professor (P < .0001). Adjusted regression models documented that women had a lower rate of publication (relative number = 0.71; 95% CI = 0.63, 0.81; P < .0001) and h-index (relative number = 0.81; 95% CI = 0.73, 0.90; P < .0001) relative to men, but there was no gender difference in grant funding. CONCLUSIONS: Women faculty acquired federal funding at similar rates as male faculty, yet lagged behind in terms of publications and their impact. Medical academia must consider how to help address ongoing gender disparities in publication records. PMID- 27276003 TI - Analysis of National Institutes of Health R01 Application Critiques, Impact, and Criteria Scores: Does the Sex of the Principal Investigator Make a Difference? AB - PURPOSE: Prior text analysis of R01 critiques suggested that female applicants may be disadvantaged in National Institutes of Health (NIH) peer review, particularly for renewals. NIH altered its review format in 2009. The authors examined R01 critiques and scoring in the new format for differences due to principal investigator (PI) sex. METHOD: The authors analyzed 739 critiques-268 from 88 unfunded and 471 from 153 funded applications for grants awarded to 125 PIs (76 males, 49 females) at the University of Wisconsin-Madison between 2010 and 2014. The authors used seven word categories for text analysis: ability, achievement, agentic, negative evaluation, positive evaluation, research, and standout adjectives. The authors used regression models to compare priority and criteria scores, and results from text analysis for differences due to PI sex and whether the application was for a new (Type 1) or renewal (Type 2) R01. RESULTS: Approach scores predicted priority scores for all PIs' applications (P < .001), but scores and critiques differed significantly for male and female PIs' Type 2 applications. Reviewers assigned significantly worse priority, approach, and significance scores to female than male PIs' Type 2 applications, despite using standout adjectives (e.g., "outstanding," "excellent") and making references to ability in more critiques (P < .05 for all comparisons). CONCLUSIONS: The authors' analyses suggest that subtle gender bias may continue to operate in the post-2009 NIH review format in ways that could lead reviewers to implicitly hold male and female applicants to different standards of evaluation, particularly for R01 renewals. PMID- 27276004 TI - Is Science Built on the Shoulders of Women? A Study of Gender Differences in Contributorship. AB - PURPOSE: Women remain underrepresented in the production of scientific literature, and relatively little is known regarding the labor roles played by women in the production of knowledge. This study examined labor roles by gender using contributorship data from science and medical journals published by the Public Library of Science (PLOS), which require each author to indicate their contribution to one or more of the following tasks: (1) analyzed the data, (2) conceived and designed the experiments, (3) contributed reagents/materials/analysis tools, (4) performed the experiments, and (5) wrote the paper. METHOD: The authors analyzed contribution data from more than 85,000 articles published between 2008 and 2013 in PLOS journals with respect to gender using both descriptive and regression analyses. RESULTS: Gender was a significant variable in determining the likelihood of performing a certain task associated with authorship. Women were significantly more likely to be associated with performing experiments, and men were more likely to be associated with all other authorship roles. This holds true controlling for academic age: Although experimentation was associated with academically younger scholars, the gap between male and female contribution to this task remained constant across academic age. Inequalities were observed in the distribution of scientific labor roles. CONCLUSIONS: These disparities have implications for the production of scholarly knowledge, the evaluation of scholars, and the ethical conduct of science. Adopting the practice of identifying contributorship rather than authorship in scientific journals will allow for greater transparency, accountability, and equitable allocation of resources. PMID- 27276005 TI - Factors Associated With Attainment of Specialty Board Qualifications and Doctor of Medical Science Degrees Among Japanese Female Doctors. AB - PURPOSE: Specialty board qualifications or doctor of medical science (DMSc) degrees are essential for women's promotion to leadership positions in medicine in Japan. The authors examined what personal and professional characteristics of female doctors were associated with attainment of specialty board qualifications and DMSc degrees. METHOD: This study was based on alumnae surveys of 13 private medical schools in Japan conducted from 2009 to 2011 and investigating 882 alumnae who had at least one child (mean age 47 years). Multinomial logistic regression models were applied to investigate factors associated with attainment of specialty board qualifications alone, DMSc degrees alone, and both, compared with attainment of neither specialty board qualifications nor DMSc degrees. RESULTS: In total, 34% of the sample obtained both specialty board qualifications and DMSc degrees, 33% obtained specialty board qualifications only, 9% obtained DMSc degrees only, and 24% obtained neither. A one-year increase in age at the time of first birth was associated with an increased likelihood of attaining a specialty board qualification and/or a DMSc versus having neither qualification (P < .0001). Women who resigned from their jobs instead of taking maternity leave at the time of first childbirth had a significantly lower likelihood ratio of obtaining specialty board qualifications either alone or in conjunction with DMSc degrees (P < .0001). CONCLUSIONS: Earlier age and job resignation at the time of first childbirth among physician-mothers in Japan were associated with failure to attain specialty board qualifications and DMSc degrees, with important implications for future career advancement. PMID- 27276006 TI - Using Qualitative Research as a Means to an Effective Survey Instrument. PMID- 27276007 TI - Inequities in Academic Compensation by Gender: A Follow-up to the National Faculty Survey Cohort Study. AB - PURPOSE: Cross-sectional studies have demonstrated gender differences in salaries within academic medicine. No research has assessed longitudinal compensation patterns. This study sought to assess longitudinal patterns by gender in compensation, and to understand factors associated with these differences in a longitudinal cohort. METHOD: A 17-year longitudinal follow-up of the National Faculty Survey was conducted with a random sample of faculty from 24 U.S. medical schools. Participants employed full-time at initial and follow-up time periods completed the survey. Annual pretax compensation during academic year 2012-2013 was compared by gender. Covariates assessed included race/ethnicity; years since first academic appointment; retention in academic career; academic rank; departmental affiliation; percent effort distribution across clinical, teaching, administrative, and research duties; marital and parental status; and any leave or part-time status in the years between surveys. RESULTS: In unadjusted analyses, women earned a mean of $20,520 less than men (P = .03); women made 90 cents for every dollar earned by their male counterparts. This difference was reduced to $16,982 (P = .04) after adjusting for covariates. The mean difference of $15,159 was no longer significant (P = .06) when adjusting covariates and for those who had ever taken a leave or worked part-time. CONCLUSIONS: The continued gender gap in compensation cannot be accounted for by metrics used to calculate salary. Institutional actions to address these disparities include both initial appointment and annual salary equity reviews, training of senior faculty and administrators to understand implicit bias, and training of women faculty in negotiating skills. PMID- 27276008 TI - An Integrated Framework for Gender Equity in Academic Medicine. AB - In 2008, the National Institutes of Health funded 14 R01 grants to study causal factors that promote and support women's biomedical careers. The Research Partnership on Women in Biomedical Careers, a multi-institutional collaboration of the investigators, is one product of this initiative.A comprehensive framework is needed to address change at many levels-department, institution, academic community, and beyond-and enable gender equity in the development of successful biomedical careers. The authors suggest four distinct but interrelated aspects of culture conducive to gender equity: equal access to resources and opportunities, minimizing unconscious gender bias, enhancing work-life balance, and leadership engagement. They review the collection of eight articles in this issue, which each address one or more of the four dimensions of culture. The articles suggest that improving mentor-mentee fit, coaching grant reviewers on unconscious bias, and providing equal compensation and adequate resources for career development will contribute positively to gender equity in academic medicine.Academic medicine must adopt an integrated perspective on culture for women and acknowledge the multiple facets essential to gender equity. To effect change, culture must be addressed both within and beyond academic health centers (AHCs). Leaders within AHCs must examine their institutions' processes, resources, and assessment for fairness and transparency; mobilize personnel and financial resources to implement evidence-based initiatives; and assign accountability for providing transparent progress assessments. Beyond AHCs, organizations must examine their operations and implement change to ensure parity of funding, research, and leadership opportunities as well as transparency of assessment and accreditation. PMID- 27276009 TI - Comparing Trainee and Staff Perceptions of Patient Safety Culture. AB - PURPOSE: The Accreditation Council for Graduate Medical Education implemented the Clinical Learning Environment Review (CLER) program to evaluate and improve the learning environment in teaching hospitals. Hospitals receive a report after a CLER visit with observations about patient safety, among other domains, the accuracy of which is unknown. Thus, the authors set out to identify complementary measures of trainees' patient safety experience. METHOD: In 2014, they administered the Hospital Survey on Patient Safety Culture to residents and fellows and general staff at 10 hospitals in an integrated health system. The survey measured perceptions of patient safety in 12 domains and incorporated two outcome measures (number of medical errors reported and overall patient safety). Domain scores were calculated and compared between trainees and staff. RESULTS: Of 1,426 trainees, 926 responded (65% response rate). Of 18,815 staff, 12,015 responded (64% response rate). Trainees and staff scored five domains similarly communication openness, facility management support for patient safety, organizational learning/continuous improvement, teamwork across units, and handoffs/transitions of care. Trainees scored four domains higher than staff nonpunitive response to error, staffing, supervisor/manager expectations and actions promoting patient safety, and teamwork within units. Trainees scored three domains lower than staff-feedback and communication about error, frequency of event reporting, and overall perceptions of patient safety. CONCLUSIONS: Generally, trainees had comparable to more favorable perceptions of patient safety culture compared with staff. They did identify opportunities for improvement though. Hospitals can use perceptions of patient safety culture to complement CLER visit reports to improve patient safety. PMID- 27276010 TI - Modular, Nondegenerate Polyprotein Scaffolds for Atomic Force Spectroscopy. PMID- 27276011 TI - Integrated Analysis of the Roles of Long Noncoding RNA and Coding RNA Expression in Sheep (Ovis aries) Skin during Initiation of Secondary Hair Follicle. AB - Initiation of hair follicle (HF) is the first and most important stage of HF morphogenesis. However the precise molecular mechanism of initiation of hair follicle remains elusive. Meanwhile, in previous study, the more attentions had been paid to the function of genes, while the roles of non-coding RNAs (such as long noncoding RNA and microRNA) had not been described. Therefore, the roles of long noncoding RNA(LncRNA) and coding RNA in sheep skin during the initiation of sheep secondary HF were integrated and analyzed, by using strand-specific RNA sequencing (ssRNA-seq).A total of 192 significant differentially expressed genes were detected, including 67 up-regulated genes and 125 down-regulated genes between stage 0 and stage 1 of HF morphogenesis during HF initiation. Only Wnt2, FGF20 were just significant differentially expressed among Wnt, Shh, Notch and BMP signaling pathways. Further expression profile analysis of lncRNAs showed that 884 novel lncRNAs were discovered in sheep skin expression profiles. A total of 15 lncRNAs with significant differential expression were detected, 6 up regulated and 9 down-regulated. Among of differentially expressed genes and LncRNA, XLOC002437 lncRNA and potential target gene COL6A6 were all significantly down-regulated in stage 1. Furthermore, by using RNAhybrid, XLOC005698 may be as a competing endogenous RNA ''sponges" oar-miR-3955-5p activity. Gene Ontology and KEGG pathway analyses indicated that the significantly enriched pathway was peroxisome proliferator-activated receptors (PPARs) pathway (corrected P-value < 0.05), indicating that PPAR pathway is likely to play significant roles during the initiation of secondary HF.Results suggest that the key differentially expressed genes and LncRNAs may be considered as potential candidate genes for further study on the molecular mechanisms of HF initiation, as well as supplying some potential values for understanding human hair disorders. PMID- 27276013 TI - Hydrogen bonding induced distortion of CO3 units and kinetic stabilization of amorphous calcium carbonate: results from 2D (13)C NMR spectroscopy. AB - Systematic correlation in alkaline-earth carbonate compounds between the deviation of the CO3 units from the perfect D3h symmetry and their (13)C nuclear magnetic resonance (NMR) chemical shift anisotropy (CSA) parameters is established. The (13)C NMR CSA parameters of amorphous calcium carbonate (ACC) are measured using two-dimensional (13)C phase adjusted spinning sidebands (PASS) NMR spectroscopy and are analyzed on the basis of this correlation. The results indicate a distortion of the CO3 units in ACC in the form of an in-plane displacement of the C atom away from the centroid of the O3 triangle, resulting from hydrogen bonding with the surrounding H2O molecules, without significant out of-plane displacement. Similar distortion for all C atoms in the structure of ACC suggests a uniform spatial disposition of H2O molecules around the CO3 units forming a hydrogen-bonded amorphous network. This amorphous network is stabilized against crystallization by steric frustration, while additives such as Mg presumably provide further stabilization by increasing the energy of dehydration. PMID- 27276012 TI - Penta-EF-Hand Protein Peflin Is a Negative Regulator of ER-To-Golgi Transport. AB - Luminal calcium regulates vesicle transport early in the secretory pathway. In ER to-Golgi transport, depletion of luminal calcium leads to significantly reduced transport and a buildup of budding and newly budded COPII vesicles and vesicle proteins. Effects of luminal calcium on transport may be mediated by cytoplasmic calcium sensors near ER exits sites (ERES). The penta-EF-hand (PEF) protein apoptosis-linked gene 2 (ALG-2) stabilizes sec31A at ER exit sites (ERES) and promotes the assembly of inner and outer shell COPII components. However, in vitro and intact cell approaches have not determined whether ALG-2 is a negative or positive regulator, or a regulator at all, under basal physiological conditions. ALG-2 interacts with another PEF protein, peflin, to form cytosolic heterodimers that dissociate in response to calcium. However, a biological function for peflin has not been demonstrated and whether peflin and the ALG 2/peflin interaction modulates transport has not been investigated. Using an intact, single cell, morphological assay for ER-to-Golgi transport in normal rat kidney (NRK) cells, we found that depletion of peflin using siRNA resulted in significantly faster transport of the membrane cargo VSV-G. Double depletion of peflin and ALG-2 blocked the increased transport resulting from peflin depletion, demonstrating a role for ALG-2 in the increased transport. Furthermore, peflin depletion caused increased targeting of ALG-2 to ERES and increased ALG-2/sec31A interactions, suggesting that peflin may normally inhibit transport by preventing ALG-2/sec31A interactions. This work identifies for the first time a clear steady state role for a PEF protein in ER-to-Golgi transport-peflin is a negative regulator of transport. PMID- 27276014 TI - A C-H Insertion Approach to Functionalized Cyclopentenones. AB - Cyclopentenones are synthetically versatile structures, and their straightforward construction from alkynone substrates by employing synthetically streamlining C-H insertion is conceptually appealing and of high synthetic potential. But, its implementation is very limited. Herein we report a Au-catalyzed version, which affords 2-bromocyclopent-2-en-1-ones with a broad scope and synthetically desirable diastereoselectivities. The proposed key intermediate capable of the observed insertion into unactivated C-H bonds is a fully functionalized gold vinylidene, which is generated via a novel intermolecular strategy. This flexible access of likely gold vinylidenes opens various opportunities to explore their versatile reactivities. PMID- 27276015 TI - Educational intervention for collecting sputum for tuberculosis: a quasi experimental study. AB - OBJECTIVE: to evaluate the quality of the sputum sample before and after the Nursing guidance to patients. METHODS: this is a quasi-experimental research design, single group type, before and after, non-randomized study. The study enrolled patients with suspected pulmonary tuberculosis, respiratory symptomatic patients for over three weeks, aged over 18 years, of both genders and without tuberculosis history in the last two years. The educational intervention consisted of individualized guidance on the collection of sputum sample, which was based on the guidelines of the Ministry of Health of Brazil and on the explanatory folder delivery. RESULTS: in this study participated 138 patients with suspected pulmonary tuberculosis. The results showed significant increase of the samples with purulent particles, volume greater than 5 mL and increased rate of patients diagnosed with tuberculosis, after the educational intervention. CONCLUSION: it was shown that after the educational intervention, it was observed sputum samples with better quality, with satisfactory aspect and volume for the effectiveness of the bacilloscopic examination. PMID- 27276016 TI - Indicators to assess the quality of programs to prevent occupational risk for tuberculosis: are they feasible? AB - OBJECTIVE: to analyze the feasibility of quality indicators for evaluation of hospital programs for preventing occupational tuberculosis. METHOD: a descriptive cross-sectional study. We tested indicators for evaluating occupational tuberculosis prevention programs in six hospitals. The criterion to define feasibility was the time spent to calculate the indicators. RESULTS: time spent to evaluate the indicators ranged from 2h 52min to 15h11min 24sec. The indicator for structure evaluation required less time; the longest time was spent on process indicators, including the observation of healthcare workers' practices in relation to the use of N95 masks. There was an hindrance to test one of the indicators for tuberculosis outcomes in five situations, due to the lack of use of tuberculin skin test in these facilities. The time requires to calculate indicators in regarding to the outcomes for occupational tuberculosis largely depends upon the level of organizational administrative structure for gathering data. PMID- 27276017 TI - Vulnerability to alcohol consumption, spiritual transcendence and psychosocial well-being: test of a theory. AB - OBJECTIVE: to demonstrate the relations among vulnerability, self-transcendence and well-being in the young adult population and the effect of each of these variables on the adoption of low-risk consumption conducts. METHOD: quantitative and cross-sectional correlation study using structural equations analysis to test the relation among the variables. RESULTS: an inverse relation was evidenced between vulnerability to alcohol consumption and spiritual transcendence (beta 0.123, p 0.025) and a direct positive relation between spiritual transcendence and psychosocial well-being (beta 0.482, p 0.000). CONCLUSIONS: the relations among the variables spiritual transcendence, vulnerability to alcohol consumption and psychosocial well-being, based on Reed's Theory, are confirmed in the population group of young college students, concluding that psychosocial well being can be achieved when spiritual transcendence is enhanced, as the vulnerability to alcohol consumption drops. OBJETIVO: demonstrar as relacoes entre vulnerabilidade, autotranscendencia e bem-estar na populacao adulta jovem e o efeito de cada uma destas variaveis na adocao de condutas de baixo risco de consumo. METODO: estudo quantitativo, transversal do tipo correlacional que utilizou a analise estatistica de Equacoes Estruturais para comprovar a relacao entre as variaveis. RESULTADOS: evidenciou-se uma relacao inversa entre a vulnerabilidade ao consumo do alcool e a transcendencia espiritual (beta-0.123, p 0.025) e uma relacao direta positiva entre a transcendencia espiritual e o bem estar psicossocial (beta 0.482, p 0.000). Conclusoes: as relacoes das variaveis transcendencia espiritual, vulnerabilidade ao consumo do alcool e bem-estar psicossocial, fundamentadas na Teoria de Reed, sao confirmadas no grupo populacional de jovens adultos universitarios, concluindo que e possivel alcancar o bem-estar psicossocial quando se incrementa a transcendencia espiritual, enquanto a vulnerabilidade ao consumo do alcool se reduz. OBJETIVO: demostrar las relaciones entre vulnerabilidad, autotrascendencia y bienestar en la poblacion adulta joven y el efecto de cada una de estas variables en la adopcion de conductas de bajo riesgo de consumo. METODO: estudio de abordaje cuantitativo, trasversal de tipo correlacional que utilizo el analisis estadistico de Ecuaciones Estructurales para la comprobacion de la relacion entre las variables. RESULTADOS: se evidencio relacion inversa entre la vulnerabilidad al consumo de alcohol y la trascendencia espiritual (beta-0.123, p 0.025) y una relacion directa positiva entre la trascendencia espiritual y el bienestar psicosocial (beta 0.482, p 0.000). CONCLUSIONES: las relaciones de las variables trascendencia espiritual, vulnerabilidad al consumo de alcohol y bienestar psicosocial, fundamentadas en la Teoria de Reed, son confirmadas en el grupo poblacional de adultos jovenes universitarios, concluyendo que es posible alcanzar el bienestar psicosocial cuando se incrementa la trascendencia espiritual, en tanto que la vulnerabilidad al consumo de alcohol se reduce. PMID- 27276018 TI - Satisfaction with medication in coronary disease treatment: psychometrics of the Treatment Satisfaction Questionnaire for Medication. AB - OBJECTIVE: to psychometrically test the Brazilian version of the Treatment Satisfaction Questionnaire for Medication - TSQM (version 1.4), regarding ceiling and floor effect, practicability, acceptability, reliability and validity. METHODS: participants with coronary heart disease (n=190) were recruited from an outpatient cardiology clinic at a university hospital in Southeastern Brazil and interviewed to evaluate their satisfaction with medication using the TSQM (version 1.4) and adherence using the Morisky Self-Reported Measure of Medication Adherence Scale and proportion of adherence. The Ceiling and Floor effect were analyzed considering the 15% worst and best possible TSQM scores; Practicability was assessed by time spent during TSQM interviews; Acceptability by proportion of unanswered items and participants who answered all items; Reliability through the Cronbach's alpha coefficient and Validity through the convergent construct validity between the TSQM and the adherence measures. RESULTS: TSQM was easily applied. Ceiling effect was found in the side effects domain and floor effect in the side effects and global satisfaction domains. Evidence of reliability was close to satisfied in all domains. The convergent construct validity was partially supported. CONCLUSIONS: the Brazilian TSQM presents evidence of acceptability and practicability, although its validity was weakly supported and adequate internal consistency was observed for one domain. PMID- 27276019 TI - Pharmaceutical interventions in medications prescribed for administration via enteral tubes in a teaching hospital. AB - OBJECTIVE: to analyze the impact of guidelines regarding errors in medications prescribed for administration through enteral tubes. METHOD: quantitative study, in three phases, undertaken in internal medicine, neurology and an intensive care unit in a general teaching hospital. In Phase 1, the following was undertaken: a protocol for dilution and unit-dose repackaging and administration for 294 medications via enteral tubes; a decision flowchart; operational-standard procedures for dilution and unit-dose repackaging of oral pharmaceutical forms and for administration of medications through enteral tubes. In phase 2, errors in 872 medications prescribed through enteral tubes, in 293 prescriptions for patients receiving inpatient treatment between March and June, were investigated. This was followed by training of the teams in relation to the guidelines established. In Phase 3, pharmaceutical errors and interventions in 945 medications prescribed through enteral tubes, in 292 prescriptions of patients receiving inpatient treatment between August and September, were investigated prospectively. The data collected, in a structured questionnaire, were compiled in the Microsoft Office Excel(r) program, and frequencies were calculated. RESULTS: 786 errors were observed, 63.9% (502) in Phase 2, and 36.1% (284) in Phase 3. In Phase 3, a reduction was ascertained in the frequency of prescription of medications delivered via enteral tubes, medications which were contraindicated, and those for which information was not available. CONCLUSION: guidelines and pharmaceutical interventions were determined in the prevention of errors involving medications delivered through enteral tubes. OBJETIVO: analisar o impacto de diretrizes sobre erros em medicamentos prescritos para administracao via sondas enterais. METODO: estudo quantitativo, em tres fases, realizado em clinica medica, neurologia e unidade de terapia intensiva de hospital geral universitario. Na Fase 1 elaborou-se: protocolo de diluicao, unitarizacao - transformacao e administracao para 294 medicamentos via sondas enterais; fluxograma decisorio; procedimentos operacionais-padrao de diluicao e unitarizacao de formas farmaceuticas orais e de administracao de medicamentos via sondas enterais. Na Fase 2 investigou-se, retrospectivamente, erros em 872 medicamentos prescritos via sondas enterais, em 293 prescricoes de pacientes internados de marco a junho. Seguiu-se capacitacao das equipes sobre diretrizes estabelecidas. Na Fase 3 investigou-se, prospectivamente, erros e intervencoes farmaceuticas em 945 medicamentos prescritos via sondas enterais, em 292 prescricoes de pacientes internados de agosto a setembro. Dados coletados, em formulario estruturado, foram compilados no programa Microsoft Office Excel(r) e calculadas as frequencias. RESULTADOS: foram observados 786 erros, 63,9% (502) na Fase 2 e 36,1% (284) na Fase 3. Na Fase 3 verificou-se reducao na frequencia de prescricao de medicamentos, via sondas enterais, contraindicados e sem informacoes disponiveis. CONCLUSAO: diretrizes e intervencoes farmaceuticas foram determinantes na prevencao dos erros de medicamentos via sondas enterais. OBJETIVO: analizar el impacto de directrices sobre errores en medicamentos prescritos para administracion via sondas enterales. METODO: estudio cuantitativo, en tres fases, realizado en una clinica medica-neurologia y en unidad de terapia intensiva de un hospital general universitario. En la Fase 1 se elaboro: protocolo de dilucion, reenvasado - transformacion y administracion para 294 medicamentos via sondas enterales; diagrama de flujo de decision; procedimientos operacionales estandar de dilucion y reenvasado - transformacion de formas farmaceuticas orales y de administracion de medicamentos via sondas enterales. En la Fase 2 se investigo, retrospectivamente, errores en 872 medicamentos prescritos via sondas enterales, en 293 prescripciones de pacientes internados de marzo a junio. La continuacion, capacitacion de los equipos sobre directrices establecidas. En la Fase 3 se investigo, prospectivamente, errores e intervenciones farmaceuticas en 945 medicamentos prescritos via sondas enterales, en 292 prescripciones de pacientes internados de agosto a septiembre. Datos fueron colectados en un formulario estructurado, compilados en el programa Microsoft Office Excel(r) y se calcularon las frecuencias. RESULTADOS: se observaron 786 errores, 63,9% (502) en la Fase 2 y 36,1% (284) en la Fase 3. En la Fase 3 se verifico una reduccion en la frecuencia de prescripcion de medicamentos, via sondas enterales, contraindicados y sin informaciones disponibles. CONCLUSION: las directrices e intervenciones farmaceuticas fueron determinantes en la prevencion de los errores de medicamentos via sondas enterales. PMID- 27276020 TI - Qualitative Description of Global Health Nursing Competencies by Nursing Faculty in Africa and the Americas. AB - OBJECTIVE: to analyze qualitative comments from four surveys asking nursing faculty to rate the importance of 30 global health competencies for undergraduate nursing programs. METHOD: qualitative descriptive study that included 591 individuals who responded to the survey in English (49 from Africa and 542 from the Americas), 163 who responded to the survey in Spanish (all from Latin America), and 222 Brazilian faculty who responded to the survey in Portuguese. Qualitative comments were recorded at the end of the surveys by 175 respondents to the English survey, 75 to the Spanish survey, and 70 to the Portuguese survey. Qualitative description and a committee approach guided data analysis. RESULTS: ten new categories of global health competencies emerged from the analysis. Faculty also demonstrated concern about how and when these competencies could be integrated into nursing curricula. CONCLUSION: the additional categories should be considered for addition to the previously identified global health competencies. These, in addition to the guidance about integration into existing curricula, can be used to guide refinement of the original list of global health competencies. Further research is needed to seek consensus about these competencies and to develop recommendations and standards to guide nursing curriculum development. PMID- 27276021 TI - Complications of central venous catheter in patients transplanted with hematopoietic stem cells in a specialized service. AB - OBJECTIVE: to identify the model, average length of stay on site and complications of central venous catheter in patients undergoing transplant of hematopoietic stem cells and verify the corresponding relationship between the variables: age, gender, medical diagnosis, type of transplant, implanted catheter and insertion site. METHOD: a retrospective and quantitative study with a sample of 188 patients transplanted records between 2007 and 2011. RESULTS: the majority of patients used Hickman catheter with an average length of stay on site of 47.6 days. The complication fever/bacteremia was significant in young males with non Hodgkin's lymphoma undergoing autologous transplant, which remained with the device for a long period in the subclavian vein. CONCLUSION: nurses should plan with their team the minimum waiting time, recommended between the catheter insertion and start of the conditioning regimen, as well as not to extend the length of time that catheter should be on site and undertake their continuing education, focusing on the prevention of complications. PMID- 27276022 TI - MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation. AB - MicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We demonstrate that endogenous or over expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. We report that there is a "seed region" of moR-21 as well as a "seed match region" in the target gene 3'UTR that are indispensable for moR-21-mediated gene down-regulation. We further demonstrate that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. Taken together, these findings provide the first evidence that microRNA offset RNA alters gene expression and is biologically active. PMID- 27276023 TI - Determination of the Preassembled Nucleating Units That Are Critical for the Crystal Growth of the Metal-Organic Framework CdIF-4. AB - Identifying the form and role of the chemical species that traverse the stages of crystallization is critical to understanding the formation process of coordination polymers. Herein, we report the combined use of in situ atomic force microscopy and mass spectrometry to identify preformed, complex, cadmium 2 ethylimidazole containing solution species in the growth solution of the cadmium 2-ethylimidazolate metal-organic framework CdIF-4, and show that they are critical in the surface nucleation for the crystal growth of this material. Surface nucleation appears to be instigated by these [Cdx (CH3 CO2 )y (C5 H7 N2 /C5 H8 N2 )z ]-containing solution species and not by sole addition of the ligand molecules. The CH3 CO2 (-) or Cd(CH3 CO2 )2 groups of the former are substituted subsequently as the framework growth proceeds. Our greater understanding of such solution species and their role in crystallization will guide future syntheses of designed functional coordination polymers. PMID- 27276024 TI - Invasive Bighead and Silver Carps Form Different Sized Shoals that Readily Intermix. AB - Two species of congeneric filter-feeding microphagous carps from Asia, the bighead and the silver carp, were recently introduced to North America and have become highly invasive. These species of carp have similar food habits but the silver carp has the unique habit of jumping when disturbed. Both species have complex but poorly understood social behaviors and while both are thought to aggregate (form groups) and shoal (form tight social groups), this possibility has not yet been examined in these species. The present study examined the grouping tendencies of these species in the laboratory and the effects of fish density and species identity on it. Using nearest neighbor distance (NND) as a metric, we showed that both juvenile bighead and juvenile silver carp grouped (aggregate) strongly (P<0.05) but to different extents, and that fish density had no effect (P>0.05) on this behavior. Within aggregations, bighead carp tended to form a single large shoal while silver carp formed shoals of 2-3 individuals. Further, when tested as mixed-species groups, bighead and silver carp readily shoaled with each other but not with the common carp, which is from Eurasia and a member of another feeding guild. Due to their similar feeding strategies, we speculate that the bighead and silver carp tend to aggregate and shoal to facilitate both their foraging efforts and to avoid predation, while the differences in the size of the shoals they form may seemingly reflect their different anti-predation strategies. These complex shoaling behaviors likely influence Asian carp distribution in rivers, and thus how they might be sampled and managed. PMID- 27276025 TI - Unmeasured Confounding in Observational Studies with Multiple Treatment Arms: Comparing Emergency Department Mortality of Severe Trauma Patients by Trauma Center Level. AB - Comparing emergency department mortality across different levels of trauma care (nontrauma centers, level I and II centers) is important in evaluating regionalized care. Patient population characteristics differ across different levels of trauma care and it is essential to adjust for baseline covariates to make valid comparisons. Propensity score matching has been established as a more robust method to infer causal relationship in observational studies than conventional regression adjustment. We designed and implemented a three group matching methodology. First, we conducted optimal pair matching between the treatment group (nontrauma centers) and the first control group (level I trauma centers); second, we conducted optimal pair matching between the nontrauma centers and the second control group (level II trauma centers); the final step was to link the two sets of matched pairs by the common treatment subjects to form matched triplets. We then implemented a sensitivity analysis with three treatment arms, Lu's imputation based method, to assess the impact due to potential unmeasured confounding. The results showed that if the most severe adult trauma patients treated in nontrauma centers were to be treated in level I or II trauma centers, the odds of emergency department death would be reduced dramatically (odds ratio [OR] = 0.61 and 0.49). There was no difference between being treated in level I or II trauma centers. The sensitivity analysis revealed that the positive association between being treated at level I or II trauma centers and the reduced odds of mortality would remain present even in the presence of strong unmeasured confounding. PMID- 27276026 TI - Commentary: Can't WaSH Without Water: Instrumental Variables Evidence from a Randomized Trial. PMID- 27276027 TI - Commentary: Matched Instrumental Variables: A Possible Solution to Severe Confounding in Matched Observational Studies? PMID- 27276028 TI - Estimating the Effect of School Water, Sanitation, and Hygiene Improvements on Pupil Health Outcomes. AB - BACKGROUND: We conducted a cluster-randomized water, sanitation, and hygiene trial in 185 schools in Nyanza province, Kenya. The trial, however, had imperfect school-level adherence at many schools. The primary goal of this study was to estimate the causal effects of school-level adherence to interventions on pupil diarrhea and soil-transmitted helminth infection. METHODS: Schools were divided into water availability groups, which were then randomized separately into either water, sanitation, and hygiene intervention arms or a control arm. School-level adherence to the intervention was defined by the number of intervention components-water, latrines, soap-that had been adequately implemented. The outcomes of interest were pupil diarrhea and soil-transmitted helminth infection. We used a weighted generalized structural nested model to calculate prevalence ratio. RESULTS: In the water-scarce group, there was evidence of a reduced prevalence of diarrhea among pupils attending schools that adhered to two or to three intervention components (prevalence ratio = 0.28, 95% confidence interval: 0.10, 0.75), compared with what the prevalence would have been had the same schools instead adhered to zero components or one. In the water-available group, there was no evidence of reduced diarrhea with better adherence. For the soil transmitted helminth infection and intensity outcomes, we often observed point estimates in the preventive direction with increasing intervention adherence, but primarily among girls, and the confidence intervals were often very wide. CONCLUSIONS: Our instrumental variable point estimates sometimes suggested protective effects with increased water, sanitation, and hygiene intervention adherence, although many of the estimates were imprecise. PMID- 27276029 TI - Brief Report: Plasma Concentrations of Perfluorooctane Sulfonamide and Time-to pregnancy Among Primiparous Women. AB - BACKGROUND: A previous study reported a negative association between perfluorooctane sulfonamide (PFOSA) concentrations and fecundability. METHODS: We examined this association among women enrolled in the Norwegian Mother and Child Cohort Study (MoBa), in 2003-2004. This analysis was restricted to 451 primiparous women to avoid bias due to previous pregnancy. Self-reported time-to pregnancy (TTP) and plasma were obtained around 18 weeks of gestation. Approximately half of the women had measurable PFOSA levels; missing values were multiply imputed. We used the logistic analogue of discrete-time survival analysis to examine the adjusted association between PFOSA, other perfluoroalkyl substances, and TTP. RESULTS: The median-measured PFOSA concentration was 0.03 ng/ml (interquartile range = 0.02, 0.07). The age and body mass index-adjusted association between an interquartile distance increase in PFOSA and TTP was 0.91 (95% confidence interval = 0.71, 1.17). Imputation of missing PFOSA resulted in similar estimates. No association was observed with other perfluoroalkyl substances. CONCLUSION: Based on a weakly decreased fecundability odds ratio, we found only limited support for an association between plasma PFOSA concentrations and TTP among primiparous women. See Video Abstract at http://links.lww.com/EDE/B79. PMID- 27276030 TI - How Are Mate Preferences Linked with Actual Mate Selection? Tests of Mate Preference Integration Algorithms Using Computer Simulations and Actual Mating Couples. AB - Prior mate preference research has focused on the content of mate preferences. Yet in real life, people must select mates among potentials who vary along myriad dimensions. How do people incorporate information on many different mate preferences in order to choose which partner to pursue? Here, in Study 1, we compare seven candidate algorithms for integrating multiple mate preferences in a competitive agent-based model of human mate choice evolution. This model shows that a Euclidean algorithm is the most evolvable solution to the problem of selecting fitness-beneficial mates. Next, across three studies of actual couples (Study 2: n = 214; Study 3: n = 259; Study 4: n = 294) we apply the Euclidean algorithm toward predicting mate preference fulfillment overall and preference fulfillment as a function of mate value. Consistent with the hypothesis that mate preferences are integrated according to a Euclidean algorithm, we find that actual mates lie close in multidimensional preference space to the preferences of their partners. Moreover, this Euclidean preference fulfillment is greater for people who are higher in mate value, highlighting theoretically-predictable individual differences in who gets what they want. These new Euclidean tools have important implications for understanding real-world dynamics of mate selection. PMID- 27276031 TI - Stable Isotope Dilution Assays for Clinical Analyses of Folates and Other One Carbon Metabolites: Application to Folate-Deficiency Studies. AB - Folate deficiency is generally accepted as a potential direct or indirect risk factor for diseases including spina bifida, coronary heart diseases, malfunctions of the central nervous system, and cancer. The direct inclusion of folates in the methylation cycle, including the remethylation of homocysteine and regeneration of S-adenosylmethionine, underlines the importance of these vitamins and other components of one-carbon metabolism. Therefore, the aim of the present study was to develop a multiple stable isotope dilution assay (SIDA) for the respective analytes in plasma and tissue samples to allow for a closer look at the interaction between a severe folate deficiency and local folate status, as well as further interactions with circulating S-adenosylmethionine, S adenosylhomocysteine, and homocysteine. The analytical methods were based on SIDAs coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis using the deuterated folates [2H4]-5-methyltetrahydrofolic acid, [2H4]-5 formyltetrahydrofolic acid, [2H4]-tetrahydrofolic acid, [2H4]-10-formylfolic acid, and [2H4]-folic acid and the deuterated one-carbon metabolites [2H4] homocysteine, [2H4]-S-adenosylhomocysteine, and [2H3]-S-adenosylmethionine as internal standards. Three analytical methods have been developed for the analysis of homocysteine, S-adenosylmethionine, S-adenosylhomocysteine, and six folate vitamers. Validation data for the analysis of C1-metabolites in plasma and tissue samples or folate analysis in tissue samples revealed excellent sensitivity, precision, and recovery for all analytes studied. The miniaturized methods using sample volumes as low as 50 MUL and weighed portions of 5-25 mg will allow the assessment of the status of folates and additional biomarkers of impaired one carbon metabolism during folate deficiency. PMID- 27276032 TI - Interfacial Coupling-Induced Ferromagnetic Insulator Phase in Manganite Film. AB - Interfaces with subtle differences in atomic and electronic structures in perovskite ABO3 heterostructures often yield intriguingly different properties, yet their exact roles remain elusive. Here, we report an integrated study of unusual transport, magnetic, and structural properties of Pr0.67Sr0.33MnO3 film on SrTiO3 substrate. The variations in the out-of-plane lattice constant and BO6 octahedral rotation across the Pr0.67Sr0.33MnO3/SrTiO3 interface strongly depend on the thickness of the Pr0.67Sr0.33MnO3 film. In the 12 nm film, a new interface sensitive ferromagnetic polaronic insulator (FI') phase is formed during the cubic-to-tetragonal phase transition of SrTiO3, apparently due to the enhanced electron-phonon interaction and atomic disorder in the film. The transport properties of the FI' phase in the 30 nm film are masked because of the reduced interfacial coupling and smaller interface-to-volume ratio. This work demonstrates how thickness-dependent interfacial coupling leads to the formation of a theoretically predicted ferromagnetic-polaronic insulator, as illustrated in a new phase diagram, that is otherwise ferromagnetic metal (FM) in bulk form. PMID- 27276033 TI - Effect of Core/Shell Interface on Carrier Dynamics and Optical Gain Properties of Dual-Color Emitting CdSe/CdS Nanocrystals. AB - Two-color emitting colloidal semiconductor nanocrystals (NCs) are of interest for applications in multimodal imaging, sensing, lighting, and integrated photonics. Dual color emission from core- and shell-related optical transitions has been recently obtained using so-called dot-in-bulk (DiB) CdSe/CdS NCs comprising a quantum-confined CdSe core embedded into an ultrathick (~7-9 nm) CdS shell. The physical mechanism underlying this behavior is still under debate. While a large shell volume appears to be a necessary condition for dual emission, comparison between various types of thick-shell CdSe/CdS NCs indicates a critical role of the interface "sharpness" and the presence of potential barriers. To elucidate the effect of the interface morphology on the dual emission, we perform side-by side studies of CdSe/CdS DiB-NCs with nominally identical core and shell dimensions but different structural properties of the core/shell interface arising from the crystal structure of the starting CdSe cores (zincblende vs wurtzite). While both structures exhibit dual emission under comparable pump intensities, NCs with a zincblende core show a faster growth of shell luminescence with excitation fluence and a more readily realized regime of amplified spontaneous emission (ASE) even under "slow" nanosecond excitation. These distinctions can be linked to the structure of the core/shell interface: NCs grown from the zincblende cores contain a ~3.5 nm thick zincblende CdS interlayer, which separates the core from the wurtzite CdS shell and creates a potential barrier for photoexcited shell holes inhibiting their relaxation into the core. This helps maintain a higher population of shell states and simplifies the realization of dual emission and ASE involving shell-based optical transitions. PMID- 27276036 TI - [Not Available]. PMID- 27276034 TI - Evolution of High Cellulolytic Activity in Symbiotic Streptomyces through Selection of Expanded Gene Content and Coordinated Gene Expression. AB - The evolution of cellulose degradation was a defining event in the history of life. Without efficient decomposition and recycling, dead plant biomass would quickly accumulate and become inaccessible to terrestrial food webs and the global carbon cycle. On land, the primary drivers of plant biomass deconstruction are fungi and bacteria in the soil or associated with herbivorous eukaryotes. While the ecological importance of plant-decomposing microbes is well established, little is known about the distribution or evolution of cellulolytic activity in any bacterial genus. Here we show that in Streptomyces, a genus of Actinobacteria abundant in soil and symbiotic niches, the ability to rapidly degrade cellulose is largely restricted to two clades of host-associated strains and is not a conserved characteristic of the Streptomyces genus or host associated strains. Our comparative genomics identify that while plant biomass degrading genes (CAZy) are widespread in Streptomyces, key enzyme families are enriched in highly cellulolytic strains. Transcriptomic analyses demonstrate that cellulolytic strains express a suite of multi-domain CAZy enzymes that are coregulated by the CebR transcriptional regulator. Using targeted gene deletions, we verify the importance of a highly expressed cellulase (GH6 family cellobiohydrolase) and the CebR transcriptional repressor to the cellulolytic phenotype. Evolutionary analyses identify complex genomic modifications that drive plant biomass deconstruction in Streptomyces, including acquisition and selective retention of CAZy genes and transcriptional regulators. Our results suggest that host-associated niches have selected some symbiotic Streptomyces for increased cellulose degrading activity and that symbiotic bacteria are a rich biochemical and enzymatic resource for biotechnology. PMID- 27276035 TI - Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial. AB - Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600MUg/L) or lower (100-200MUg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort. PMID- 27276037 TI - [Rhetoric of quantification: tuberculosis, statistics and the labor world in Colombia, 1916-1946]. AB - This article examines the application of tuberculosis statistics in the Colombian medical discourse, the gap between these statistics and data officially published, as well as the relationship between the quantitative dynamics, the anti-tuberculosis campaign and the objectivation of tuberculosis in labor world in Colombia over the period ranging from the beginning of the campaign (1916) to the inclusion of tuberculosis in the list of professional diseases (1946). It also analyzes the critical role that labor statistics played in the first developments of the Colombian social security system and in the definition of professional diseases. These historical processes were studied according to its insertion in the international context. PMID- 27276038 TI - [The emergence of Aids in Amazonas]. AB - This article analyzes the historical, social, and political context in which Aids emerged in the Brazilian state of Amazonas, and how local responses were shaped by changes taking place on a national political level. Documental sources from governmental and non-governmental institutions were researched, and the information was supplemented and clarified by oral sources - testimonials of activists and health professionals/managers who have led the organization of healthcare for people with HIV/Aids in the state. This research reveals that the lack of coordination between healthcare institutions and the dearth of any real political will to fight the epidemic in the state have hampered the planning and execution of public strategies and actions covering the whole welfare system in the state. PMID- 27276039 TI - [Philanthropy and welfare policies for the families of people with leprosy in the Brazilian state of Goias, 1920-1962]. AB - This article analyzes the root causes of the shortage of social support for the relatives of people with leprosy, especially their children, in the state of Goias, Central West region of Brazil, between 1920 and 1962. It focuses on the constitution of discourses that defined the medical and philanthropic care for the children of people isolated in leper colonies as a problem, and how this process resulted in the organization of the Society for the Welfare of Lepers and Defense Against Leprosy, and the construction of Afranio de Azevedo children's home in Goiania, the state capital. These elements are directly associated with the construction of a new approach in the regional history and social and medical policies for leprosy. PMID- 27276040 TI - [A giant field of death: medical and scientific controversies about the cholera morbus epidemic of 1855]. AB - The article examines the cholera morbus epidemic that afflicted the province of Pernambuco, Brazil, in 1855, focusing on the medical and scientific controversies about how the disease spread, which split medical opinion into two camps: contagion and infection. Documents and reports produced by the Society of Medicine of Pernambuco and the General Public Health Board were analyzed, based on which it was possible to describe the official medical and sanitation program, involving engineers, scientists, and physicians, designed to plan a salubrious city - a model of civilization that combined redeveloping the urban space and disseminating new habits amongst the local people. It is essentially an exercise in observing a science and a society as they take shape. PMID- 27276041 TI - [From the Belle Epoque to the city of vice: the fight against syphilis in Belem, Para, 1921-1924]. AB - This article analyzes the fight against syphilis in Belem, capital of the Brazilian state of Para, between 1921 and 1924. When Instituto de Profilaxia e Doencas Venereas (Institute for Prophylaxis and Venereal Diseases) was founded, headed by Dr. Heraclides de Souza Araujo, many restrictions were imposed on prostitution in a bid to make prostitutes partners in the city's sanitation reform. The documents produced by the institute and published in newspapers of the day reveal the various clashes that occurred between doctors, the civil police force, and prostitutes, highlighting the prostitutes' attitudes to state intervention in their activities. PMID- 27276042 TI - [The leprosy "drama": Governador Valadares, public health policies, and their territorial implications in the 1980s]. AB - The incidence of leprosy in Governador Valadares, Brazil, in the 1980s spurred this town to pioneer the introduction of polychemotherapy. The aim of this research was to understand how the different actors involved in this context interacted, especially the employees and patients at the Special Public Health Service. To identify the territories that these interactions inevitably constituted, a variety of theoretical instruments were used, including dramatism (Burke) and performance (Turner). By taking a theatrical metaphor, we sought to find out the dynamics by which the different actors took the stage and established their most significant relationships in a dynamic process of constituted and reconstituted territories. PMID- 27276043 TI - [The sertao remediated: the clash between the elite of Goias and sanitation thinking, 1910-1920]. AB - In the early decades of the twentieth century, when health started becoming an issue on the political agenda, Arthur Neiva and Belisario Penna travelled to the sertao semi-arid region of Goias state, Brazil, to diagnose the population's state of health, particularly highlighting the spread of Chagas disease and the decadence of the sertao. The political elite in the state reacted to the sanitarians' findings. This article observes the controversy played out in the pages of A Informacao Goiana magazine. The publication supported the region's interests, because its leaders were sure that it was down to the people of Goias to reveal the truth about the sertao, its people, and its potentialities. PMID- 27276044 TI - [Introduction to a social cartography: the journal Revista de Saude Publica, 1967 to 1977]. AB - Through reliance on a social cartography method based on Karl Mannheim's sociology of knowledge, the article analyzes the first ten issues of Revista de Saude Publica, published by the University of Sao Paulo. Articles and editorials are mapped in order to understand the period's transformations. In the realm of the journal's editorial line, tensions are noted between complying with the principles of the institution and international transformations, which demanded an openness to interdisciplinary topics. Special focus is placed on sub-fields, dominated by an epidemiology that was in flux as it absorbed new knowledge in the context of the formation of the field of public health. PMID- 27276045 TI - [Art, mental health, and public healthcare: profile of a care culture in the history of Sao Paulo city]. AB - By studying the inclusion of artistic and cultural activities in the care provided throughout the history of public mental healthcare in greater Sao Paulo, Brazil, we can better understand and characterize the practices adopted in the Psychosocial Care Centers in the city today. Experiments carried out between the 1920s and 1990s are investigated, based on bibliographic research. The contemporary data were obtained from research undertaken at 126 workshops at 21 Psychosocial Care Centers in the same city between April 2007 and April 2008. The findings indicate that the current trend in mental healthcare, whose clinical perspective spans the realms of art and mental health and has territorial ramifications, has maintained some of the features encountered in earlier mental healthcare experiments. PMID- 27276046 TI - [Communication and mental health: a discursive analysis of posters of the National Anti-Asylum Campaign Movement in Brazil]. AB - The article analyzes two posters that with the same slogan - "Asylums nevermore" promote National Anti-Asylum Day. The analysis was based on principles of the symptomatology of social discourse, articulating analytical concepts and practices arising from the French School and the pragmatic dimension of discourse analysis. The results revealed affirmation strategies of the movement for the qualification and exacerbation of the issues of the enunciation and other enunciators, namely political actors of the anti-asylum movement and their allies. It also reveals the attempt to disqualify competitive discourse, especially that which discloses the serious problems of its institutional models, but also by juxtaposing the positive presence of the issuers and enunciators of the posters. PMID- 27276047 TI - [The translation of knowledge in the ambit of international cooperation: the experience of Fiocruz in introducing health technologies to Haiti]. AB - To investigate the debate about South-South cooperation, we conducted an analysis of a course on the Management of Physical and Technological Resources in Health given in Haiti as part of a partnership between Fiocruz and the Brazilian and Haitian ministries of health with the aim of enabling the functioning of the units built by Brazil, contributing to the sustainability of the tripartite cooperation project. The course format - designing interventions to overcome real problems identified by the students - resulted in the development of eight intervention pre-projects geared towards overcoming management problems at the reference community hospitals built by Brazil in Haiti. PMID- 27276048 TI - ["Tet asanm pou la sante": ethnographic notes on international cooperation for health in Haiti]. AB - This article discusses the functioning of a health-oriented development project pursued in an emergency situation and its impacts beyond its stated goals. The tripartite project between Brazil, Haiti, and Cuba was designed to strengthen Haiti's health and epidemiologic surveillance system, introduced in 2010 as part of the aid effort after the earthquake. An essentially ethnographic perspective is taken, with a focus on describing the practices and perspectives of the agents involved in the program. The networks of agents were mapped out, paying particular attention to translators, drivers, and journalists, who were understood as being "cooperation brokers". Finally, the article discusses the project's position in the broader context of international health initiatives in Haiti. PMID- 27276049 TI - [Sociabilities, networks and the circulation of knowledges in the creation of a "psy scope" in Argentina during the inter-war period (Santa Fe, 1919-1943)]. AB - This article presents the findings of a research study on the construction of a psy scientific field in Argentina during the inter-war period, with a focus on subnational spaces. After 1920, the mental hygiene movement, in its different disciplinary manifestations, became notable in the public sphere, in university education and - belatedly - in healthcare policies, in an expansion that led to the creation of an autonomous field with its own logic. I argue that the creation of this "psy field" - while it was as yet inexistent - was largely due to the strength of sociability networks that facilitated the management of resources and institutional spaces of power, making it possible for the field to become independent and established. PMID- 27276050 TI - [Between images and texts: manuals as a praxis of knowledge]. AB - We investigate a series of writing genres from the Enlightenment in Portugal, especially between 1720 and 1800, comprehending them as manuals of knowledge, and we highlight some of the meanings of the images in these writings that were widely circulated in the Portuguese-speaking world. PMID- 27276051 TI - Antimicrobial Properties of an Immunomodulator - 15 kDa Human Granulysin. AB - Granulysin, a cationic protein expressed by human natural killer cells and cytotoxic T lymphocytes, is a mediator for drug-induced Stevens-Johnson syndrome and graft-versus-host disease. Some 15 kDa granulysin are processed into 9 kDa forms and sequestered in cytolytic granules, while others are constitutively secreted into body fluids. Both 9 and 15 kDa granulysin have been shown to be a serum marker for cell-mediated immunity. Furthermore, 15 kDa is able to activate monocyte differentiation. However, its antimicrobial properties have not been clearly addressed. Here, we report a novel method to prepare both the soluble 9 and 15 kDa granulysin and show that the 15 kDa form is more effective than the 9 kDa form in exerting specific antimicrobial activity against Pseudomonas aeruginosa within a range of few micromolars. We also show that the 15 kDa granulysin is able to hyperpolarize the membrane potential and increase membrane permeability of treated bacteria. Interestingly, the bactericidal activity and membrane permeability of the granulysins were markedly reduced at lower pH (pH 5.4) as a result of probable increase in hydrophobicity of the granulysins. Additionally, we've also shown the granulysin to inhibit biofilm formation by P. aeruginosa. These results suggest that the 15 kDa granulysin exhibits a novel mechanism in bacteria killing in a way that's different from most antimicrobial peptides. Our novel granulysin preparation methodology will be useful for further study of action mechanisms of other antimicrobial, cytotoxic and immunomodulating properties in granulysin-mediated diseases. PMID- 27276053 TI - In Situ Visualization of Lipid Raft Domains by Fluorescent Glycol Chitosan Derivatives. AB - Lipid rafts are highly ordered small microdomains mainly composed of glycosphingolipids, cholesterol, and protein receptors. Optically distinguishing lipid raft domains in cell membranes would greatly facilitate the investigations on the structure and dynamics of raft-related cellular behaviors, such as signal transduction, membrane transport (endocytosis), adhesion, and motility. However, current strategies about the visualization of lipid raft domains usually suffer from the low biocompatibility of the probes, invasive detection, or ex situ observation. At the same time, naturally derived biomacromolecules have been extensively used in biomedical field and their interaction with cells remains a long-standing topic since it is closely related to various fundamental studies and potential applications. Herein, noninvasive visualization of lipid raft domains in model lipid bilayers (supported lipid bilayers and giant unilamellar vesicles) and live cells was successfully realized in situ using fluorescent biomacromolecules: the fluorescein isothiocyanate (FITC)-labeled glycol chitosan molecules. We found that the lipid raft domains in model or real membranes could be specifically stained by the FITC-labeled glycol chitosan molecules, which could be attributed to the electrostatic attractive interaction and/or hydrophobic interaction between the probes and the lipid raft domains. Since the FITC-labeled glycol chitosan molecules do not need to completely insert into the lipid bilayer and will not disturb the organization of lipids, they can more accurately visualize the raft domains as compared with other fluorescent dyes that need to be premixed with the various lipid molecules prior to the fabrication of model membranes. Furthermore, the FITC-labeled glycol chitosan molecules were found to be able to resist cellular internalization and could successfully visualize rafts in live cells. The present work provides a new way to achieve the imaging of lipid rafts and also sheds new light on the interaction between biomacromolecules and lipid membranes. PMID- 27276052 TI - In-Utero Low-Dose Irradiation Leads to Persistent Alterations in the Mouse Heart Proteome. AB - Prenatal exposure to stress such as increased level of reactive oxygen species or antiviral therapy are known factors leading to adult heart defects. The risks following a radiation exposure during fetal period are unknown, as are the mechanisms of any potential cardiac damage. The aim of this study was to gather evidence for possible damage by investigating long-term changes in the mouse heart proteome after prenatal exposure to low and moderate radiation doses. Pregnant C57Bl/6J mice received on embryonic day 11 (E11) a single total body dose of ionizing radiation that ranged from 0.02 Gy to 1.0 Gy. The offspring were sacrificed at the age of 6 months or 2 years. Quantitative proteomic analysis of heart tissue was performed using Isotope Coded Protein Label technology and tandem mass spectrometry. The proteomics data were analyzed by bioinformatics and key changes were validated by immunoblotting. Persistent changes were observed in the expression of proteins representing mitochondrial respiratory complexes, redox and heat shock response, and the cytoskeleton, even at the low dose of 0.1 Gy. The level of total and active form of the kinase MAP4K4 that is essential for the embryonic development of mouse heart was persistently decreased at the radiation dose of 1.0 Gy. This study provides the first insight into the molecular mechanisms of cardiac impairment induced by ionizing radiation exposure during the prenatal period. PMID- 27276054 TI - Decoupled Evolution between Senders and Receivers in the Neotropical Allobates femoralis Frog Complex. AB - During acoustic communication, an audible message is transmitted from a sender to a receiver, often producing changes in behavior. In a system where evolutionary changes of the sender do not result in a concomitant adjustment in the receiver, communication and species recognition could fail. However, the possibility of an evolutionary decoupling between sender and receiver has rarely been studied. Frog populations in the Allobates femoralis cryptic species complex are known for their extensive morphological, genetic and acoustic variation. We hypothesized that geographic variation in acoustic signals of A. femoralis was correlated with geographic changes in communication through changes in male-male recognition. To test this hypothesis, we quantified male call recognition using phonotactic responses to playback experiments of advertisement calls with two, three and four notes in eight localities of the Amazonian basin. Then, we reconstructed the ancestral states of call note number in a phylogenetic framework and evaluated whether the character state of the most recent common ancestor predicted current relative responses to two, three and four notes. The probability of a phonotactic response to advertisement calls of A. femoralis males was strongly influenced by the call mid-frequency and the number of notes in most populations. Positive phonotaxis was complete for calls from each individual's population, and in some populations, it was also partial for allotopic calls; however, in two populations, individuals equally recognized calls with two, three or four notes. This evidence, in conjunction with our results from phylogenetic comparative methods, supports the hypothesis of decoupled evolution between sender and receiver in the male-male communication system of the A. femoralis complex. Thus, signal recognition appears to evolve more slowly than the calls. PMID- 27276055 TI - [Mantle cell lymphoma]. PMID- 27276057 TI - Correction: Characterization and Functional Analysis of 4-Coumarate:CoA Ligase Genes in Mulberry. AB - [This corrects the article DOI: 10.1371/journal.pone.0155814.]. PMID- 27276056 TI - A Milestone: Approval of CEUS for Diagnostic Liver Imaging in Adults and Children in the USA. AB - The approval of microbubbles with the inert gas sulfur hexafluoride (SF6) and a palmitic acid shell (SonoVue((r)), Bracco Geneva, CH) for the diagnostic imaging of liver tumors in adults and children by the FDA in the United States represents a milestone for contrast-enhanced ultrasound (CEUS).This warrants a look back at the history of the development of CEUS. The first publications based on echocardiographic observations of right ventricular contrast phenomena caused by tiny air bubbles following i. v. injection of indocyanine green appeared around 1970 1 2 3. A longer period of sporadic publications but no real progress then followed since, in contrast to X-ray methods, ultrasound works quite well without a contrast agent.It is noteworthy that the foundations for further development were primarily laid in Europe. The development and approval (1991) of the contrast agent Echovist((r)) by a German contrast manufacturer for echocardiography unsuitable for passing through lungcapillaries 4 5 resulted in the first extracardiac indications, e. g. for detecting retrovesical reflux and tubal patency, in the mid-1980 s 6 7 8. The sensitivity of color Doppler was not able to compensate for the lack of an ultrasound contrast agent compared to CT with its obligatory contrast administration.Studies of SHU 508 - microbubbles of air moderately stabilized with galactose and palmitic acid - began in 1990 9 10 11 12 13 14 15 and the contrast agent was then introduced in 1995 in Germany as Levovist((r)). The most important publications by Blomley, Cosgrove, Leen, and Albrecht are named here on a representative basis 16 17 18 19 20.SHU 508 along with other US contrast agents provided impressive proof of the superiority of CEUS for the diagnosis of liver metastases. However, practical application remained complicated and required skill and technical know-how because of a lack of suitable software on US units 21 22 23 24 25. The monograph regarding the use of contrast agent in the liver by Wermke and Gabetamann is impressive but unfortunately only available in German 26. In addition to being applied in the heart and the liver, CEUS was first used in transcranial applications 27 and in vessels 28, the kidneys 29, and the breast 30. Measurements at transit times were also of particular interest 31. It was difficult to convince ultrasound device manufacturers of the need to adapt US units to US contrast agents and not vice versa.The breakthrough came with low MI phase contrast inversion and the introduction of SonoVue((r)) in many European countries in 2001. This more stable US contrast agent is easy to use and is becoming indispensable in diagnostic imaging of the liver 32 33 34 35 36 37 38 39 40. Studies have shown its excellent tolerability 41 and diagnostic reliability comparable to that of MDCT and MRI in the liver 42 43. Today it would be unimaginable to diagnose liver tumors without CEUS 44. This also applies to very small lesions 45 46.EFSUMB published the first CEUS guidelines in 2004 47 which have since been reissued and divided into hepatic 48 and extrahepatic applications 49. The first recommendations regarding quantitative assessment have also been published 50.The increasing scientific interest in CEUS is evident based on the greater number of PubMed hits for Echovist((r)) (ca. 130), Levovist((r)) (ca. 500) and SonoVue((r)) (ca. 1500) as well as on the fact that publications regarding CEUS comprise almost 20 % of UiM/EJU articles in the last 10 years. The number of CEUS articles in UiM/EJU continues to be high 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75.In the clinical reality, CEUS has been able to become established alongside CT and MRI according to the saying "better is the enemy of good" 76 as the method of choice after B-mode ultrasound in the evaluation of liver tumor malignancy in Germany, where the technically challenging method is promoted. In the case of unclear CT and MRI findings, CEUS performed by an experienced examiner/clinician often provides the solution, particularly in the case of small lesions, and is the last resort before US-guided biopsy 45 46. However, there is a lack of competent CEUS examiners and Germany continues to be the world champion of X-ray examinations with no noticeable reverse trend. In almost every doctor's office and hospital, ultrasound costs are by far not fully covered, resulting in an extremely high frequency of CT use with CT being available to everyone regardless of insurance status.The USA is now in the starting position for CEUS. It will be exciting to see how the method will develop there. The FDA's decision to approve sulfur hexafluoride (Lumason((r)) = SonoVue((r))) should be considered against the background of the radiation exposure caused by CT examinations and the fact that MRI using gadolinium-containing contrast agents is no longer considered noninvasive because of nephrogenic systemic fibrosis (NSF) and the accumulation of the agent in the cerebrum. An essential point of the campaign regarding the avoidance of diagnostic radiation exposure triggered in the USA by the publications of Brenner et al. 77 78 was that the agent was approved for use in the liver even for children 79 80 - still off label in Europe - without additional comprehensive studies due to the available scientific results and the very low side effects profile of Lumason((r)) (= SonoVue((r))). It is admittedly unclear why other indications (except the heart which has been approved since 2014) are excluded even though the microbubbles as a pure blood pool contrast agent can be diagnostically used in the entire vascular system and bed of all organs. To our knowledge, there is no such restriction on the approval of X-ray contrast agents.Like echocardiography and emergency ultrasound, CEUS began in Europe but will probably only establish its final diagnostic value as a "reimport".This is a major opportunity to permanently define the role of Ultrasound as a highly valuable, patient-centered imaging method in the German health care system.This may prompt some of our international readers to reflect upon the role of CEUS in their own countries. PMID- 27276058 TI - Rapid Recovery of CD3+CD8+ T Cells on Day 90 Predicts Superior Survival after Unmanipulated Haploidentical Blood and Marrow Transplantation. AB - BACKGROUND: Rapid immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is significantly associated with lower infection, relapse and possibly secondary malignancy rates. The aim of this study was to investigate the role of peripheral lymphocyte subsets, especially CD3+CD8+ cytotoxic T cell recovery, in predicting transplant outcomes, including the overall survival (OS) and non-relapse mortality (NRM) rates after unmanipulated haploidentical blood and marrow transplantation (HBMT). METHODS: Peripheral blood samples were obtained from 214 HBMT recipients with hematological malignancies. The peripheral lymphocyte subsets (CD3+ T cells, CD3+CD4+ helper T cells, CD3+CD8+ cytotoxic T cells, and CD19+ B cells) were analyzed by flow cytometry at days 30, 60, 90, 180, 270 and 360 after HBMT. RESULTS: The CD3+CD8+ cytotoxic T cell recovery at day 90 (CD3+CD8+-90) was correlated with bacterial infection (P = 0.001), NRM (P = 0.001), leukemia-free survival (LFS, P = 0.005), and OS (P = 0.001) at a cutoff value of 375 cells/MUL CD3+CD8+ T cells. The incidence of bacterial infection in patients with the CD3+CD8+-90 at >=375 cells/MUL was significantly lower than that of cases with the CD3+CD8+-90 at <375 cells/MUL after HBMT (14.6% versus 41.6%, P<0.001). Multivariate analysis showed the rapid recovery of CD3+CD8+ T cells at day 90 after HBMT was strongly associated with a lower incidence of NRM (HR = 0.30; 95% CI: 0.15-0.60; P = 0.000) and superior LFS (HR = 0.51; 95% CI: 0.32-0.82; P = 0.005) and OS (HR = 0.38; 95% CI: 0.23-0.63; P = 0.000). CONCLUSION: The results suggest that the rapid recovery of CD3+CD8+ cytotoxic T cells at day 90 following HBMT could predict superior transplant outcomes. PMID- 27276059 TI - An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database. AB - BACKGROUND: This study evaluated the effects of atypical antipsychotic drugs and selective serotonin reuptake inhibitors (SSRIs) on the corrected QT (QTc) interval using a large database obtained from clinical settings. Additionally, the effects of factors including age on QTc intervals were estimated. METHODS: Using an open-access QT database (ECG-ViEW), QTc-lengthening effects of 14 selected atypical antipsychotics and SSRIs were compared to those of a positive control drug, cilostazol, and a negative control drug, diazepam. We also evaluated effects of age, sexgender, and select electrolyte levels on observed QTc intervals. RESULTS: The frequency of QTc prolongation with the pooled data of the 14 study drugs was lower than that with cilostazol (age-adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) = 0.27-0.69), but no significant difference was found relative to when compared with that with diazepam (age adjusted OR = 0.89, 95% CI = 0.55-1.47). Furthermore, administration of the 14 study drugs significantly increased the QTc interval by 2.89 ms after each 10 year age increment (p-value < 0.0001). CONCLUSIONS: This study suggests that atypical antipsychotic drugs and SSRIs are less likely to be associated with QTc prolongation in clinical settings. In addition, age showed a significant association with the QTc interval. Further studies with well-characterized cohorts are warranted. PMID- 27276060 TI - Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma. AB - Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID- 27276061 TI - Investigating the Role of TNF-alpha and IFN-gamma Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages. AB - Macrophage produced inducible nitric oxide synthase (iNOS) is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO) by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS), iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF-alpha). To understand the synergistic effect of IFN-gamma and TNF-alpha activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN gamma priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-gamma and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-gamma priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-alpha contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-gamma stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced. PMID- 27276062 TI - CD24 Expression May Play a Role as a Predictive Indicator and a Modulator of Cisplatin Treatment Response in Head and Neck Squamous Cellular Carcinoma. AB - Platinum-based therapy is most often used to treat advanced cases of head and neck cancers, but only a small fraction of the patient population responds to cisplatin, with a median survival time of less than a year. Although gene signatures and molecular etiology of head and neck cancers have been previously described, none of them are predictive indicators of cisplatin treatment response in particular. Therefore, currently, there is a lack of clinically employable predictive indicators of the disease beyond HPV status to specifically predict patients' response to platinum-based therapy. It beckons a substantial effort to look for predictive indicators of cisplatin treatment response. In this regard, CD24 expression level appears to be a significant molecular phenotype of cisplatin-resistant residual cells in laryngeal carcinoma lines. CD24 expression level directly affects cisplatin sensitivity and affects the expression of critical apoptotic, stem and drug resistance genes. A relatively small retrospective patient tumor analysis suggests that CD24 high tumors go on to show an unfavorable response to cisplatin treatment. Overall, based on the strength of further analysis, CD24 presents a strong rationale to be utilized as a predictive indicator to stratify head and neck cancer patients for platinum-based therapy. It also provides a rationale for using CD24 as a therapeutic adjuvant target along with standard cisplatin therapy. PMID- 27276064 TI - MicroRNA-200b Impacts Breast Cancer Cell Migration and Invasion by Regulating Ezrin-Radixin-Moesin. AB - BACKGROUND Ezrin-radixin-moesin (ERM) plays an important role in multiple links of tumors. It also involved in breast cancer invasion and metastasis, and might be a potential biomarker of breast cancer. Another study suggested that ERM expression was regulated directly by miR-200c, and had a critical role in miR 200c suppressing cell migration. This study aimed to investigate the effect of miR-200b on ERM expression in a breast cancer cell line and its influence on invasion and metastasis ability in vitro. MATERIAL AND METHODS Breast cancer cell lines MCF-7 and MDA-MB-231 with different metastatic potentials were selected as a model. MiR-200b overexpression or inhibition was achieved by LipofectamineTM 2000-mediated miRNA transfection. RT-PCR was used to test miR-200b level, while Western blot was selected to detect ERM protein expression. Wound healing assay and Transwell assay were performed to determine cell migration and invasion ability. RESULTS RT-PCR revealed that miR-200b level in MDA-MB-231 was obviously lower than that in MCF-7, while Western blot analysis showed that ERM expression was significantly higher. MiR-200b inhibition by transfection in MCF-7 markedly decreased miR-200b level, elevated ERM expression, and enhanced cell migration and invasion. MiR-200b overexpression in MDA-MB-231 obviously increased miR-200b level, reduced ERM expression, and weakened cell migration and invasion. CONCLUSIONS MiR-200b participates in breast cancer cell migration and invasion through regulating ERM in MCF-7 and MDA-MB-231. PMID- 27276065 TI - Red Light Treatment in an Axotomy Model of Neurodegeneration. AB - Red light has been shown to provide neuroprotective effects. Axotomizing the optic nerve initiates retinal ganglion cell (RGC) degeneration, and an early marker of this is dendritic pruning. We hypothesized that 670 nm light can delay axotomy-induced dendritic pruning in the retinal explant. To test this hypothesis, we monitored the effects of 670 nm light (radiant exposure of 31.7 J cm(-2) ), on RGC dendritic pruning in retinal explants from C57BL/6J mice, at 40 min, 8 h and 16 h post axotomy. For sham-treated retinae, area under the Sholl curve, peak of the Sholl curve and dendritic length at 8 h post axotomy showed statistically significant reductions by 42.3% (P = 0.008), 29.8% (P = 0.007) and 38.4% (P = 0.038), respectively, which were further reduced after 16 h by 40.56% (P < 0.008), 33.9% (P < 0.007), 45.43% (P < 0.006), respectively. Dendritic field area was also significantly reduced after 16 h, by 44.23% (P < 0.019). Such statistically significant reductions were not seen in light-treated RGCs at 8 or 16 h post axotomy. The results demonstrate the ability of 670 nm light to partially prevent ex vivo dendropathy in the mouse retina, suggesting that it is worth exploring as a treatment option for dendropathy-associated neurodegenerative diseases, including glaucoma and Alzheimer's disease. PMID- 27276063 TI - Melanopsin Regulates Both Sleep-Promoting and Arousal-Promoting Responses to Light. AB - Light plays a critical role in the regulation of numerous aspects of physiology and behaviour, including the entrainment of circadian rhythms and the regulation of sleep. These responses involve melanopsin (OPN4)-expressing photosensitive retinal ganglion cells (pRGCs) in addition to rods and cones. Nocturnal light exposure in rodents has been shown to result in rapid sleep induction, in which melanopsin plays a key role. However, studies have also shown that light exposure can result in elevated corticosterone, a response that is not compatible with sleep. To investigate these contradictory findings and to dissect the relative contribution of pRGCs and rods/cones, we assessed the effects of light of different wavelengths on behaviourally defined sleep. Here, we show that blue light (470 nm) causes behavioural arousal, elevating corticosterone and delaying sleep onset. By contrast, green light (530 nm) produces rapid sleep induction. Compared to wildtype mice, these responses are altered in melanopsin-deficient mice (Opn4-/-), resulting in enhanced sleep in response to blue light but delayed sleep induction in response to green or white light. We go on to show that blue light evokes higher Fos induction in the SCN compared to the sleep-promoting ventrolateral preoptic area (VLPO), whereas green light produced greater responses in the VLPO. Collectively, our data demonstrates that nocturnal light exposure can have either an arousal- or sleep-promoting effect, and that these responses are melanopsin-mediated via different neural pathways with different spectral sensitivities. These findings raise important questions relating to how artificial light may alter behaviour in both the work and domestic setting. PMID- 27276066 TI - Fullerene (C60)-based tumor-targeting nanoparticles with "off-on" state for enhanced treatment of cancer. AB - The traditional drug delivery systems always suffer from the unexpected drug release during circulation and the sluggish release of drug in target site. To address the problem, an "off-on" type drug delivery system with precise control was developed in this study. Doxorubicin (DOX) was covalently conjugated to fullerene (C60) nanoaggregates via a reactive oxygen species (ROS)-sensitive thioketal linker (C60-DOX NPs), and then the hydrophilic shell (Distearoyl-sn glycero-3-phosphoethanolamine-PEG-CNGRCK2HK3HK11, DSPE-PEG-NGR) was attached to the outer surface of C60-DOX, giving it (C60-DOX-NGR NP) excellent stability in physiological solutions and active tumor-targeting capacity. C60-DOX-NGR NPs were able to entrap DOX efficiently even at acidic environment (pH5.5) when they were "off" state. In sharp contrast, when the NPs were "on" state, a large number of ROS were generated by C60, leading to the breaking of ROS-sensitive linker, thereby enabling the burst release of DOX. The "off" or "on" state of C60-DOX-NGR NPs could be precisely remote-controlled by a 532nm laser (at a low power density) with a high spatial/temporal resolution. In the in vivo and in vitro studies, the C60-based drug delivery system with "off-on" state exhibited a high antitumor efficacy and a low toxicity to normal tissues due to its tumor targeting ability, remote-controlled drug release property and combined therapeutic effect (photodynamic therapy combined with chemotherapy). PMID- 27276067 TI - DREMECELS: A Curated Database for Base Excision and Mismatch Repair Mechanisms Associated Human Malignancies. AB - DNA repair mechanisms act as a warrior combating various damaging processes that ensue critical malignancies. DREMECELS was designed considering the malignancies with frequent alterations in DNA repair pathways, that is, colorectal and endometrial cancers, associated with Lynch syndrome (also known as HNPCC). Since lynch syndrome carries high risk (~40-60%) for both cancers, therefore we decided to cover all three diseases in this portal. Although a large population is presently affected by these malignancies, many resources are available for various cancer types but no database archives information on the genes specifically for only these cancers and disorders. The database contains 156 genes and two repair mechanisms, base excision repair (BER) and mismatch repair (MMR). Other parameters include some of the regulatory processes that have roles in these disease progressions due to incompetent repair mechanisms, specifically BER and MMR. However, our unique database mainly provides qualitative and quantitative information on these cancer types along with methylation, drug sensitivity, miRNAs, copy number variation (CNV) and somatic mutations data. This database would serve the scientific community by providing integrated information on these disease types, thus sustaining diagnostic and therapeutic processes. This repository would serve as an excellent accompaniment for researchers and biomedical professionals and facilitate in understanding such critical diseases. DREMECELS is publicly available at http://www.bioinfoindia.org/dremecels. PMID- 27276068 TI - The Human Protein Atlas - an important resource for basic and clinical research. PMID- 27276070 TI - Neopterin and hsCRP are not correlated in gestational diabetes mellitus. AB - OBJECTIVE: To determine serum neopterin and high sensitive C-reactive protein (hsCRP) levels in patients with and without gestational diabetes mellitus (GDM). METHODS: Neopterin and hsCRP levels were quantified in 28 women with GDM and 20 pregnant women with normal glucose tolerance (NGT). Postpartum neopterin and hsCRP levels were measured in a follow-up study. RESULTS: Neopterin levels were significantly higher in women with GDM than in women with NGT (15.89 +/- 8.19 nmol/L versus 10.4 +/- 3.8 nmol/L, p < 0.008, respectively), however the levels significantly decreased after delivery in GDM group (15.89 +/- 8.19 nmol/L versus 11.63 +/- 5.96 nmol/L, p < 0.001). hsCRP levels were not different between women with and without GDM (5.74 +/- 3.91 versus 5.73 +/- 3.34, p = 0.9, respectively). In contrast, hsCRP levels decreased after delivery in patients with GDM (5.74 +/- 3.91 versus 3.78 +/- 2.78, p < 0.01). Neopterin levels were correlated with maternal age (r = 0.3, p = 0.02) and fasting glucose (r = 0.4, p = 0.004), postprandial glucose (r = 0.3, p = 0.01), HbA1c (r = 0.3, p = 0.02), whereas hsCRP levels were correlated with pre-pregnancy (r = 0.3, p = 0.04) and pregnancy body mass index (r = 0.4, p = 0.008). No correlation between serum neopterin and hsCRP levels was found (p = 0.9). CONCLUSION: Neopterin levels increased in patients with GDM; hence, it may be related to inflammation. However, the lack of correlation between neopterin and hsCRP suggests the role of different attitudes of these two parameters in the course of pregnancy and GDM. PMID- 27276069 TI - Structural and Functional Characterization of a Novel Family of Cyclophilins, the AquaCyps. AB - Cyclophilins are ubiquitous cis-trans-prolyl isomerases (PPIases) found in all kingdoms of life. Here, we identify a novel family of cyclophilins, termed AquaCyps, which specifically occurs in marine Alphaproteobacteria, but not in related terrestric species. In addition to a canonical PPIase domain, AquaCyps contain large extensions and insertions. The crystal structures of two representatives from Hirschia baltica, AquaCyp293 and AquaCyp300, reveal the formation of a compact domain, the NIC domain, by the N- and C-terminal extensions together with a central insertion. The NIC domain adopts a novel mixed alpha-helical, beta-sheet fold that is linked to the cyclophilin domain via a conserved disulfide bond. In its overall fold, AquaCyp293 resembles AquaCyp300, but the two proteins utilize distinct sets of active site residues, consistent with differences in their PPIase catalytic properties. While AquaCyp293 is a highly active general PPIase, AquaCyp300 is specific for hydrophobic substrate peptides and exhibits lower overall activity. PMID- 27276071 TI - [Parkinson's Disease at the Border Between Inpatient and Outpatient Care]. AB - Parkinson's disease is characterized by a continuous spectrum of varying severity. The treatment is driven by new and sometimes highly complex therapeutic procedures. These two aspects are responsible for the blurred dividing line between outpatient and inpatient care. The aim of this article is to define criteria that should help determine the indication for inpatient or outpatient treatment. We introduce quality requirements that have already been taken into account in part in therapy modalities such as Parkinson complex treatment. The decision on the appropriate form of care affects the medical freedom of therapy, which must reconcile the legitimate interest of patients to receive optimal care with the given economic conditions. Our aim is to provide guidance on decisions on the best form of treatment in the context of changing framework conditions in the health sector. PMID- 27276072 TI - [The Geriatric Patient with Parkinson's Disease - a Neurological Challenge]. AB - Geriatric patients with Parkinson's disease (PD) represent a particular challenge in terms of diagnostics and treatment. This overview article addresses age related characteristics of this patient group and discusses particularities in PD symptoms in this age group, frequent comorbidities and the resulting polypharmacy. Questions regarding the availability of specialist and therapist care as well as end-of-life aspects are discussed. While comprehensive care structures are not always available, this patient group requires a multidisciplinary treatment team supervised by neurologists with ample experience in PD treatment. PMID- 27276073 TI - [Wearable Technique for the Assessment of Parkinson Symptoms: What's the Future?]. AB - Parkinson's disease (PD) is a multisystem disorder with a plethora of symptoms affecting the quality of life of patients in the home environment. Due to the rapid development of wearable technique in the health and fitness sector, an increasing number of such wearable devices are available to complement diagnostic strategies of PD symptoms not only in the clinical but also in the home environment. This development has clear advantages over clinical evaluation, as the latter is relatively subjective, time-consuming and costly, and provides only a snapshot of the condition. First results about the use of such technology for the assessment of PD symptoms (including bradykinesia, dyskinesia, tremor, daily activity and sleep behavior) in the home environment are promising. They suggest that these techniques can provide complementary information about the symptoms of PD patients, and have the potential to be included in future diagnostic workup concepts of routine care in PD. The use of such technique provides also the opportunity to more actively include patients into medical decision-making processes. PMID- 27276074 TI - [Perioperative Management of PD Patients]. AB - Both patients and caregivers but also treating physicians are concerned about complications along with surgical interventions. A major problem is abrupt cessation of anti-Parkinson medication, which leads to manifold disturbances, sometimes even to an akinetic crisis. There are several means to guarantee continuous dopaminergic stimulation even in patients that are not allowed to take medication orally before they undergo surgery. Amongst others rectally applied levodopa, amantadine infusions, and especially the use of a rotigotine patch are good means to overcome oral intake. Perioperative management is important due to the fact that in Germany alone each year more than 10 000 PD patients undergo surgery. Main reasons for this are fractures, but also elective interventions. Further emergency situations that cause treatment as an inpatient are psychosis, motoric disability, but also pneumonia and cardiovascular disturbances. In contrast PD patients suffer less often from cancer. PMID- 27276075 TI - Converting a Natural Protein Compartment into a Nanofactory for the Size Constrained Synthesis of Antimicrobial Silver Nanoparticles. AB - Engineered biological systems are used extensively for the production of high value and commodity organics. On the other hand, most inorganic nanomaterials are still synthesized via chemical routes. By engineering cellular compartments, functional nanoarchitectures can be produced under environmentally sustainable conditions. Encapsulins are a new class of microbial nanocompartments with promising applications in nanobiotechnology. Here, we engineer the Thermotoga maritima encapsulin EncTm to yield a designed compartment for the size constrained synthesis of silver nanoparticles (Ag NPs). These Ag NPs exhibit uniform shape and size distributions as well as long-term stability. Ambient aqueous conditions can be used for Ag NP synthesis, while no reducing agents or solvents need to be added. The antimicrobial activity of the synthesized protein coated or shell-free Ag NPs is superior to that of silver nitrate and citrate capped Ag NPs. This study establishes encapsulins as an engineerable platform for the synthesis of biogenic functional nanomaterials. PMID- 27276076 TI - Patterns in Volatile Emission of Different Aerial Parts of Caper (Capparis spinosa L.). AB - We analyzed the spontaneous volatile emission of different aerial parts of the caper (Capparis spinosa L.) by HS-SPME-GC/MS. We identified 178 different compounds of which, in different proportions based on the sample type, the main ones were (E)-beta-ocimene, methyl benzoate, linalool, beta-caryophyllene, alpha guaiene, germacrene D, bicyclogermacrene, germacrene B, (E)-nerolidol, isopropyl tetradecanoate, and hexahydrofarnesyl acetone. The multivariate statistical analyses seem to point out that the parameter leading the emission patterns is the function of the analyzed sample; the flower samples showed differences in the emission profile between their fertile and sterile portions and between the other parts of the plant. The green parts emission profiles group together in a cluster and are different from those of seeds and fruits. We also hydrodistilled fully bloomed caper flowers, whose volatile oil showed significant differences in the composition from those of other parts of the plant reported. PMID- 27276078 TI - Who Is Who: An Anomalous Predator-Prey Role Exchange between Cyprinids and Perch. AB - Piscivory in cyprinids (Cyprinidae) is extremely rare. Specifically, common bream (Abramis brama) and common carp (Cyprinus carpio) are zooplanktivorous fish in deep lentic waters. Nevertheless, we observed predation by these two cyprinids under natural conditions in the Vir Reservoir, Czech Republic. We conducted diet analysis for cyprinids caught by trawling and gillnets and the large amount of young-of-the-year (YOY) perch (Perca fluviatilis), with sizes of 37-52 mm standard length, were found in their digestive tracts. In 2010, a large amount of YOY perch caused a significant decrease in Daphnia spp. size and abundance in the reservoir. Hence, a food deficit was induced for the cyprinids, apparent also from the poor nutritional condition of common bream which was much worse than the condition of those in similar reservoirs. Common carp and common bream shifted to forced piscivory, and they utilized the YOY perch as an alternative food source. In contrast, smaller species, such as roach (Rutilus rutilus) and bleak (Alburnus alburnus), widely utilized planktonic cyanobacteria. In the following year, YOY perch occurred in significantly lower numbers and conversely, Daphnia spp. size and abundance were significantly higher. The forced piscivory was not observed. Our results indicate a switch to forced piscivory by cyprinids, which was caused by a shortage of their natural food source. Moreover, this phenomenon presents an effective mechanism for reduction in the numbers of YOY perch, ensuring the stability of the ecosystem. PMID- 27276077 TI - Comparative Effectiveness of Phosphate Binders in Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis. AB - BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. METHODS: Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at >=4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. RESULTS: Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). DISCUSSION/CONCLUSIONS: Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD-42016032945. PMID- 27276079 TI - Psychosocial Interventions for Families with Parental Cancer and Barriers and Facilitators to Implementation and Use - A Systematic Review. AB - BACKGROUND: Parental cancer has a significant impact on minor children and families. Psychosocial interventions for affected families can provide support where necessary. This systematic review aims at providing an overview of existing interventions and support programs and focuses on the systematic investigation of barriers and facilitators for using psychosocial interventions for families affected by parental cancer (PROSPERO; registration number CRD42014013020). METHODS: A search of five electronic databases (EMBASE, MEDLINE, PsycInfo, Psyndex, CINAHL) was conducted in June 2014, and updated in September 2015. We included any kind of studies reporting psychosocial support services or interventions for families affected by parental cancer. Study quality was assessed using the Mixed Method Assessment Tool. Narrative synthesis and thematic analyses were undertaken to examine the included interventions and to identify barriers and facilitators for use and implementation. RESULTS: A total of 36 studies covering 19 interventions and support services were included in the systematic review. Interventions focused on children, parents or several family members and analyses revealed a broad picture of theoretical background and primary aims. Several studies focused on developmental or implementation phases or descriptions of interventions. Other included studies reported results of evaluations using qualitative and quantitative methods. Results suggest that interventions are helpful and that participants improved in various outcomes. The thematic analyses indicate that barriers for use of support services refer to aspects concerning the patients and families, such as practical difficulties, perceived need for support or fear of stigma. Cancer patients who understood the need and benefit of support services may have used them more often. Additionally, intervention characteristics such as a flexible structure and accessibility were important to reach families affected by parental cancer. Disease characteristics and complications in collaborations were identified as potential barriers. The provision of information about interventions by clinicians and understanding the support as part of routine care seem to be key issues for implementation and use of psychosocial support. CONCLUSION: This review identified a broad number of intervention concepts for families with minor children affected by parental cancer. Findings provide a basis for existing or future psychosocial interventions to anticipate potential barriers and facilitators to implementation and use and can help to reach a wider range of families in need for support. PMID- 27276080 TI - Vitamin D Status Does Not Affect Disability Progression of Patients with Multiple Sclerosis over Three Year Follow-Up. AB - BACKGROUND AND OBJECTIVE: The risk of developing multiple sclerosis (MS) as well as MS disease activity is associated with vitamin D (25(OH)D) status. The relationship between the main functional disability hallmark of MS, disability progression, and 25(OH)D status is less well established though, especially not in MS patients with progressive disease. METHODS: This retrospective follow-up study included 554 MS patients with a serum baseline 25(OH)D level and Expanded Disability Status Scale (EDSS) with a minimum follow-up of three years. Logistic regressions were performed to assess the effect of baseline 25(OH)D status on relapse rate. Repeated measures linear regression analyses were performed to assess the effect on disability and disability progression. RESULTS: Baseline deseasonalized 25(OH)D status was associated with subsequent relapse risk (yes/no), but only in the younger MS patients (<= 37.5 years; OR = 0.872, per 10 nmol/L 25(OH)D, p = 0.041). Baseline 25(OH)D status was not significantly associated with either disability or disability progression, irrespective of MS phenotype. CONCLUSION: Within the physiological range, 25(OH)D status is just significantly associated with the occurrence of relapses in younger MS patients, but is not associated with disability or disability progression over three years follow-up. Whether high dose supplementation to supra physiological 25(OH)D levels prevents disability progression in MS should become clear from long term follow-up of supplementation studies. PMID- 27276082 TI - Temporal Trends and Spatial Variability of Vegetation Phenology over the Northern Hemisphere during 1982-2012. AB - Satellite-derived vegetation phenology has been recognized as a key indicator for detecting changes in the terrestrial biosphere in response to global climate change. However, multi-decadal changes and spatial variation of vegetation phenology over the Northern Hemisphere and their relationship to climate change have not yet been fully investigated. In this article, we investigated the spatial variability and temporal trends of vegetation phenology over the Northern Hemisphere by calibrating and analyzing time series of the satellite-derived normalized difference vegetation index (NDVI) during 1982-2012, and then further examine how vegetation phenology responds to climate change within different ecological zones. We found that during the period from 1982 to 2012 most of the high latitude areas experienced an increase in growing period largely due to an earlier beginning of vegetation growing season (BGS), but there was no significant trend in the vegetation growing peaks. The spatial pattern of phenology within different eco-zones also experienced a large variation over the past three decades. Comparing the periods of 1982-1992, 1992-2002 with 2002-2012, the spatial pattern of change rate of phenology shift (RPS) shows a more significant trend in advancing of BGS, delaying of EGS (end of growing season) and prolonging of LGS (length of growing season) during 2002-2012, overall shows a trend of accelerating change. Temperature is a major determinant of phenological shifts, and the response of vegetation phenology to temperature varied across different eco-zones. PMID- 27276083 TI - Intrauterine thrombosis of umbilical artery - case report. AB - CONTEXT: Umbilical cord thrombosis is related to greater fetal and perinatal morbidity and mortality. It is usually associated with umbilical cord abnormalities that lead to mechanical compression with consequent vascular ectasia. Its correct diagnosis and clinical management remains a challenge that has not yet been resolved. CASE REPORT: This study reports a case of umbilical artery thrombosis that occurred in the second half of a pregnancy. The umbilical cord was long, thin and overly twisted and the fetus presented severe intrauterine growth restriction. The clinical and histopathological findings from this case are described. CONCLUSIONS: This case report emphasizes the difficulty in diagnosing and clinically managing abnormalities of intrauterine life with a high chance of perinatal complications. PMID- 27276081 TI - Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data. AB - BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naive patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility. PMID- 27276085 TI - Development of a strategy of physician-patient relationship for improving care for patients with disorders of sex development: a qualitative study. AB - CONTEXT AND OBJECTIVE: Care for patients with disorders of sex development (DSD) should be provided in integrated-care centers by a multidisciplinary team. Implementation of this project within the teaching clinic routine presents several challenges: 1) difficulties in relationships between the medical team and patients and their families; 2) age, ethnic and cultural differences; 3) DSD related prejudice; and 4) physicians' anxiety. We report on a psychologist's work strategy that focused on creating arrangements that could contribute towards development of the relationship between the medical team and patients and their families, as a way of preparing the clinical staff to manage treatment of adult DSD patients. DESIGN AND SETTING: Prospective qualitative study. METHODS: Between February 2010 and April 2015, we conducted a qualitative study in the Adrenal Outpatient Clinic of Escola Paulista de Medicina (Sao Paulo, Brazil), based on interviews, team discussions and group dynamics with resident physicians, postgraduate students and attending physicians. RESULTS: Implementation of the project allowed residents to build a story of differentiated care for their patients, thus facilitating dialog between them and making it possible to address taboo topics. Sequential care provided by the same resident led patients to feel that their doctor cared for them, with individuality, continuity and a sense of interest in their story. CONCLUSION: Presence of a psychologist in the outpatient routine enabled inclusion of subjective factors in the routine of medical consultations, thus broadening the notion of healthcare for patients with DSD, facilitating bonds and providing support for difficulties faced. PMID- 27276086 TI - Correction: Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005589.]. PMID- 27276087 TI - Transcatheter intervention in a child with scimitar syndrome. AB - Scimitar syndrome is a rare congenital heart disease characterised by anomalous pulmonary venous drainage to the inferior vena cava, aortopulmonary collaterals, hypoplasia of the right lung and intracardiac defects. Surgical correction remains the gold-standard therapy. However, non-surgical intervention has been reported effective in selected cases with scimitar syndrome. We report on a one year-old boy with scimitar syndrome who underwent stepwise transcatheter intervention as an alternative treatment. Embolisation of the aortopulmonary collaterals and occlusion of the atrial septal defect were performed using detachable coils and an Amplatzer septal occluder, respectively. The patient's postcathetherisation course was uneventful. The right cardiac chamber and pulmonary arterial pressure returned to normal during follow up. PMID- 27276089 TI - Spleen and Portal Pneumatosis Secondary to Clostridium perfringens Septicemia. PMID- 27276088 TI - Development and External Validation of a Melanoma Risk Prediction Model Based on Self-assessed Risk Factors. AB - IMPORTANCE: Identifying individuals at high risk of melanoma can optimize primary and secondary prevention strategies. OBJECTIVE: To develop and externally validate a risk prediction model for incident first-primary cutaneous melanoma using self-assessed risk factors. DESIGN, SETTING, AND PARTICIPANTS: We used unconditional logistic regression to develop a multivariable risk prediction model. Relative risk estimates from the model were combined with Australian melanoma incidence and competing mortality rates to obtain absolute risk estimates. A risk prediction model was developed using the Australian Melanoma Family Study (629 cases and 535 controls) and externally validated using 4 independent population-based studies: the Western Australia Melanoma Study (511 case-control pairs), Leeds Melanoma Case-Control Study (960 cases and 513 controls), Epigene-QSkin Study (44 544, of which 766 with melanoma), and Swedish Women's Lifestyle and Health Cohort Study (49 259 women, of which 273 had melanoma). MAIN OUTCOMES AND MEASURES: We validated model performance internally and externally by assessing discrimination using the area under the receiver operating curve (AUC). Additionally, using the Swedish Women's Lifestyle and Health Cohort Study, we assessed model calibration and clinical usefulness. RESULTS: The risk prediction model included hair color, nevus density, first degree family history of melanoma, previous nonmelanoma skin cancer, and lifetime sunbed use. On internal validation, the AUC was 0.70 (95% CI, 0.67-0.73). On external validation, the AUC was 0.66 (95% CI, 0.63-0.69) in the Western Australia Melanoma Study, 0.67 (95% CI, 0.65-0.70) in the Leeds Melanoma Case Control Study, 0.64 (95% CI, 0.62-0.66) in the Epigene-QSkin Study, and 0.63 (95% CI, 0.60-0.67) in the Swedish Women's Lifestyle and Health Cohort Study. Model calibration showed close agreement between predicted and observed numbers of incident melanomas across all deciles of predicted risk. In the external validation setting, there was higher net benefit when using the risk prediction model to classify individuals as high risk compared with classifying all individuals as high risk. CONCLUSIONS AND RELEVANCE: The melanoma risk prediction model performs well and may be useful in prevention interventions reliant on a risk assessment using self-assessed risk factors. PMID- 27276091 TI - Sesquiterpenes from Inula japonica with Inhibitory Effects on Nitric Oxide Production in Murine Macrophage RAW 264.7 Cells. AB - Eight new sesquiterpenes (1-8), along with seven known sesquiterpenes (9-15), were isolated from a methanol extract of the flowers of Inula japonica. Their structures were elucidated by a combination of 1D and 2D NMR spectroscopic and HRESIMS data. All of isolates were evaluated for their inhibitory effects on nitric oxide production in LPS-induced RAW 264.7 cells, with their IC50 values ranging from 1.9 to 15.4 MUM. PMID- 27276090 TI - MicroRNA Signatures of Drought Signaling in Rice Root. AB - BACKGROUND: Drought stress is one of the most important abiotic stresses and the main constraint to rice agriculture. MicroRNA-mediated post-transcriptional gene regulation is one of the ways to establish drought stress tolerance in plants. MiRNAs are 20-24-nt regulatory RNAs that play an important role in regulating plant gene expression upon exposure to biotic and abiotic stresses. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we applied a partial root drying system as well as a complete root drying system to identify miRNAs involved in conditions of drought stress, drought signaling and wet signaling using high throughput sequencing. To this end, we produced four small RNA libraries: (1) fully-watered (WW), (2) fully-droughted (WD), and split-root systems where (3) one-half was well watered (SpWW) and (4) the other half was water-deprived (SpWD). Our analysis revealed 10,671 and 783 unique known and novel miRNA reads in all libraries, respectively. We identified, 65 (52 known + 13 novel), 72 (61 known + 11 novel) and 51 (38 known + 13 novel) miRNAs that showed differential expression under conditions of drought stress, drought signaling and wet signaling, respectively. The results of quantitative real-time PCR showed expression patterns similar to the high-throughput sequencing results. Furthermore, our target prediction led to the identification of 244, 341 and 239 unique target genes for drought-stress-, drought-signaling- and wet-signaling responsive miRNAs, respectively. CONCLUSIONS/SIGNIFICANCE: Our results suggest that miRNAs that are responsive under different conditions could play different roles in the regulation of abscisic acid signaling, calcium signaling, detoxification and lateral root formation. PMID- 27276092 TI - Serum Albumin Levels and Economic Status in Japanese Older Adults. AB - BACKGROUND: Low serum albumin levels are associated with aging and medical conditions such as cancer, liver dysfunction, inflammation, and malnutrition and might be an independent predictor of long-term mortality in healthy older populations. We tested the hypothesis that economic status is associated with serum albumin levels and explained by nutritional and health status in Japanese older adults. DESIGN: We performed a cross-sectional analysis using data from the Japan Gerontological Evaluation study (JAGES). The study participants were 6528 functionally independent residents (3189 men and 3339 women) aged >=65 years living in four municipalities in Aichi prefecture. We used household income as an indicator of economic status. Multiple linear regression was used to compare serum albumin levels in relation to household income, which was classified as low, middle, and high. Additionally, mediation by nutritional and health-related factors was analyzed in multivariable models. RESULTS: With the middle-income group as reference, participants with low incomes had a significantly lower serum albumin level, even after adjustment for sex, age, residential area, education, marital status, and household structure. The estimated mean difference was -0.17 g/L (95% confidence interval, -0.33 to -0.01 g/L). The relation between serum albumin level and low income became statistically insignificant when "body mass index", "consumption of meat or fish", "self-rated health", "presence of medical conditions", "hyperlipidemia", or "respiratory disease "was included in the model. CONCLUSION: Serum albumin levels were lower in Japanese older adults with low economic status. The decrease in albumin levels appears to be mediated by nutrition and health-related factors with low household incomes. Future studies are needed to reveal the existence of other pathways. PMID- 27276093 TI - Cost-Effectiveness of Different Cervical Screening Strategies in Islamic Republic of Iran: A Middle-Income Country with a Low Incidence Rate of Cervical Cancer. AB - OBJECTIVE: Invasive cervical cancer (ICC) is the fourth most common cancer among women worldwide. Cervical screening programs have reduced the incidence and mortality rates of ICC. We studied the cost-effectiveness of different cervical screening strategies in the Islamic Republic of Iran, a Muslim country with a low incidence rate of ICC. METHODS: We constructed an 11-state Markov model, in which the parameters included regression and progression probabilities, test characteristics, costs, and utilities; these were extracted from primary data and the literature. Our strategies included Pap smear screening and human papillomavirus (HPV) DNA testing plus Pap smear triaging with different starting ages and screening intervals. Model outcomes included lifetime costs, life years gained, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis was performed to examine the stability of the results. RESULTS: We found that the prevented mortalities for the 11 strategies compared with no screening varied from 26% to 64%. The most cost-effective strategy was HPV screening, starting at age 35 years and repeated every 10 years. The ICER of this strategy was $8,875 per QALY compared with no screening. We found that screening at 5-year intervals was also cost-effective based on GDP per capita in Iran. CONCLUSION: We recommend organized cervical screening with HPV DNA testing for women in Iran, beginning at age 35 and repeated every 10 or 5 years. The results of this study could be generalized to other countries with low incidence rates of cervical cancer. PMID- 27276094 TI - A Triboelectric-Based Artificial Basilar Membrane to Mimic Cochlear Tonotopy. AB - A triboelectric-based artificial basilar membrane (TEABM) can mimic cochlear tonotopy by triboelectrification between Kapton film and aluminum foil. The two films are stacked and clamped to form a beam structure. The TEABM tonotopy is tested using an animal model to verify the feasibility of a self-powered acoustic sensor for a prototype cochlear implant. PMID- 27276095 TI - SCIENTIFIC RESEARCH UNDER AN INTEGRATED PERSPECTIVE OF THE HUMAN BEING. PMID- 27276096 TI - THE APPROVAL OF VEDOLIZUMAB FOR THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASES IN BRAZIL: the beginning of a new biological era. PMID- 27276097 TI - GUIDELINE FOR THE MANAGEMENT OF BILE DUCT CANCERS BY THE BRAZILIAN GASTROINTESTINAL TUMOR GROUP. AB - The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers. PMID- 27276099 TI - Correction to "Diastereoselective Passerini Reaction of Biobased Chiral Aldehydes: Divergent Synthesis of Various Polyfunctionalized Heterocycles". PMID- 27276100 TI - Population aging: The transformation of societies, by Donald T. Rowling. PMID- 27276101 TI - Fundamentals of Joint Injection. AB - OBJECTIVE: Using image guidance for joint access is a valuable fundamental skill. The purpose of this article is to review fluoroscopic and ultrasound-guided techniques and the medications used for injection into the glenohumeral, elbow, wrist, hip, knee, and ankle joints. CONCLUSION: Thorough understanding of basic injection principles, knowledge of the underlying anatomy, and consideration of the advantages and disadvantages of the imaging approaches should facilitate selection of the most appropriate technique for any clinical scenario. PMID- 27276098 TI - Biophysical Characterization of Fluorotyrosine Probes Site-Specifically Incorporated into Enzymes: E. coli Ribonucleotide Reductase As an Example. AB - Fluorinated tyrosines (FnY's, n = 2 and 3) have been site-specifically incorporated into E. coli class Ia ribonucleotide reductase (RNR) using the recently evolved M. jannaschii Y-tRNA synthetase/tRNA pair. Class Ia RNRs require four redox active Y's, a stable Y radical (Y.) in the beta subunit (position 122 in E. coli), and three transiently oxidized Y's (356 in beta and 731 and 730 in alpha) to initiate the radical-dependent nucleotide reduction process. FnY (3,5; 2,3; 2,3,5; and 2,3,6) incorporation in place of Y122-beta and the X-ray structures of each resulting beta with a diferric cluster are reported and compared with wt-beta2 crystallized under the same conditions. The essential diferric-FnY. cofactor is self-assembled from apo FnY-beta2, Fe(2+), and O2 to produce ~1 Y./beta2 and ~3 Fe(3+)/beta2. The FnY. are stable and active in nucleotide reduction with activities that vary from 5% to 85% that of wt-beta2. Each FnY.-beta2 has been characterized by 9 and 130 GHz electron paramagnetic resonance and high-field electron nuclear double resonance spectroscopies. The hyperfine interactions associated with the (19)F nucleus provide unique signatures of each FnY. that are readily distinguishable from unlabeled Y.'s. The variability of the abiotic FnY pKa's (6.4 to 7.8) and reduction potentials (-30 to +130 mV relative to Y at pH 7.5) provide probes of enzymatic reactions proposed to involve Y.'s in catalysis and to investigate the importance and identity of hopping Y.'s within redox active proteins proposed to protect them from uncoupled radical chemistry. PMID- 27276102 TI - Using Wearable Video Technology to Build a Point-of-View Surgical Education Library. PMID- 27276103 TI - Absorption of SO2(g) by TDAE[O2SSO2](s) to Give TDAE[O2SS(O)2SO2](s): Related Reactions of [NR4]2[O2SSO2](s) (R = CH3, C2H5). AB - One mole equivalent of gaseous SO2 is absorbed by purple TDAE[O2SSO2](s), producing red, essentially spectroscopically pure TDAE[O2SS(O)2SO2](s); under prolonged evacuation, the product loses SO2(g), regenerating TDAE[O2SSO2](s). Similarly, [NR4]2[O2SS(O)2SO2](s) (R = Et, Me) can be prepared, albeit at lower purity, from the corresponding tetraalkylammonium dithionites (prepared by a modification of the known [NEt4]2[O2SSO2](s) preparation). While the [NEt4](+) salt is stable at rt; the [NMe4](+) salt has only limited stability at -78 degrees C. Vibrational spectra assignments for the anion in these salts were distinctly different from those for the anion in salts containing the long-known [O3SSSO3](2-) dianion, the most thermodynamically stable form of [S3O6](2-) (we prepared TDAE[O3SSSO3].H2O(s) and obtained its structure by X-ray diffraction and vibrational analyses). The best fit between the calculated ((B3PW91/6-311+G(3df) and PBE0/6-311G(d)) and experimental vibrational spectra were obtained with the dianion having the [O2SS(O)2SO2](2-) structure. Vibrational analyses of the three [O2SS(O)2SO2](2-) salts prepared in this work showed that the corresponding [O3SSO2](2-) salts were present as a ubiquitous decomposition product. The formation of these new [O2SS(O)2SO2](2-) dianion salts was predicted to be favorable for [NMe4](+) and larger cations using a combination of theoretical calculations (B3PW91/6-311+G(3df)) and volume based thermodynamics (VBT). Similar methods accounted for the greater stabilities of the TDAE(2+) and [NEt4](+) salts of [O2SS(O)2SO2](2-) compared to [NMe4]2[O2SS(O)2SO2](s) toward irreversible decomposition to the corresponding [O3SSO2](2-) salts. These salts represent the first known examples of a new class of poly(sulfur dioxide) dianion, [SO2]n(2-) in which n > 2. PMID- 27276104 TI - Chromosome Microarray. AB - Over the last half century, knowledge about genetics, genetic testing, and its complexity has flourished. Completion of the Human Genome Project provided a foundation upon which the accuracy of genetics, genomics, and integration of bioinformatics knowledge and testing has grown exponentially. What is lagging, however, are efforts to reach and engage nurses about this rapidly changing field. The purpose of this article is to familiarize nurses with several frequently ordered genetic tests including chromosomes and fluorescence in situ hybridization followed by a comprehensive review of chromosome microarray. It shares the complexity of microarray including how testing is performed and results analyzed. A case report demonstrates how this technology is applied in clinical practice and reveals benefits and limitations of this scientific and bioinformatics genetic technology. Clinical implications for maternal-child nurses across practice levels are discussed. PMID- 27276105 TI - Posttraumatic Growth After Birth Trauma: "I Was Broken, Now I Am Unbreakable". AB - PURPOSE: The aim of this study was to investigate women's experiences of posttraumatic growth following traumatic childbirth. STUDY DESIGN AND METHODS: A descriptive phenomenological study was conducted using Colaizzi's data analysis method. The Internet sample of 15 mothers was recruited from the Trauma and Birth Stress Web site. Women were asked to describe in as much detail as they could remember, their experiences of any positive changes in their beliefs or life as a result of their traumatic childbirth. RESULTS: Using Calhoun and Tedeschi's metaphor of an earthquake to help explain posttraumatic growth, the seismic waves of birth trauma had enough power to lead to four themes of posttraumatic growth revealed in this phenomenological study: (1) Opening oneself up to a new present, (2) Achieving a new level of relationship nakedness, (3) Fortifying spiritual mindedness, and (4) Forging new paths. CLINICAL IMPLICATIONS: Mothers' experiences of their personal growth after birth trauma can help inform future research that can promote posttraumatic growth in mothers. Clinicians can share results of this study with their patients to provide some hope to mothers struggling with the aftermath of a traumatic birth that some women have reported positive growth. Healthcare providers need to respect trauma survivors' struggles while at the same time permitting mothers to explore possibilities for growth. Clinicians must not, however, create the false expectation that posttraumatic growth will happen in most trauma survivors. PMID- 27276108 TI - Yellow Fever in Angola and Beyond--The Problem of Vaccine Supply and Demand. PMID- 27276110 TI - Correction: Tracking Resilience to Infections by Mapping Disease Space. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002436.]. PMID- 27276109 TI - Neonatal adverse drug reactions: an analysis of reports to the French pharmacovigilance database. AB - AIM: Term and preterm neonates are at high risk for serious adverse drug reactions (ADRs). METHODS: A descriptive study of reports registered in the French pharmacovigilance database from 1986 to 2012 were obtained. All reports concerning neonates (<=1 month of life) with direct drug exposure were retrieved. Characteristics of the reports, including reported ADR(s), drug(s) and the causality assessment using the French causality assessment method, were described. RESULTS: A total of 1688 reports were analyzed and more than half of them were classified as serious (n = 995). Median age at ADR occurrence was 9 days. Overall, 3127 ADRs were described in these reports in relation to 2238 suspect/interacting drugs. The most commonly reported system organ classes (SOCs) were injury, poisoning and procedural complications (16%), general disorders and administration site conditions (12.5%) and blood and lymphatic system disorders (12%). In the majority of ADRs reported (73%), infants fully recovered and less than 4% of neonates deceased as a consequence of the reported ADR. One out of five ADRs was associated with drug administration errors. Therapeutic classes commonly incriminated were anti-infectives, nervous system and alimentary tract drugs. Substances most frequently related to serious ADRs were zidovudine, ibuprofen and nevirapine. Among the 10 most frequently encountered drug-ADR pairs, two substances were mainly implicated, zidovudine in haematological adverse reactions and phytomenadione in maladministrations. CONCLUSIONS: Anti infective drugs, mainly antiretroviral therapy, account for the majority of ADRs reported in neonates. The specific issue of drug maladministration and medication errors remains to be addressed in neonates. PMID- 27276111 TI - Bone Reduction to Facilitate Immediate Implant Placement and Loading Using CAD/CAM Surgical Guides for Patients With Terminal Dentition. AB - The aim of this study is to present a method, using 3 computer-aided design/computer-aided manufacturing (CAD/CAM) surgical guides, to accurately obtain the desired bone reduction followed by immediate implant placements and loading for patients diagnosed with terminal dentition. Patients who had bone reduction, implants placed, and immediate loading using Anatomage Invivo 5 CAD/CAM surgical guides between the period 2013 and 2015 were evaluated retrospectively. Patients diagnosed with terminal dentition and treated using the "3-guide technique" were identified. Pre- and postsurgical images were superimposed to evaluate deviations of the bone reduction and deviations at the crest, apex, and angle of implants placed. Twenty-six implants placed in 5 patients were included in this study. The overall deviation means measured for bone reduction was 1.98 mm. The overall deviation means measured for implant placement at the crest, apex, and angle were 1.43 mm, 1.90 mm, and 4.14 degrees , respectively. The CAD/CAM surgical guide fabrication is an emerging tool that may facilitate the surgical process and aid in safe and predictable execution of bone reduction and immediate implant placement. Using 3 CAD/CAM surgical guides, a method is presented to obtain the desired bone reduction followed by immediate implant placement and loading for patients diagnosed with terminal dentition. This method may improve guide stability for patients with terminal dentition undergoing complete implant-supported treatment by taking advantage of the teeth to be extracted. PMID- 27276112 TI - Loss of CDKN2A Promoter Methylation Coincides With the Epigenetic Transdifferentiation of Uterine Myosarcomatous Cells. AB - Leiomyosarcoma is the most common type of uterine sarcoma and usually displays typical morphology. Heterologous leiomyosarcoma is the rarest variant, in which the tumor contains liposarcomatous, osteosarcomatous, or rhabdomyosarcomatous components. We have investigated the largest series of uterine leiomyosarcoma with a rhabdomyosarcomatous component and we have disclosed a molecular finding, which coincides to the process of transdifferentiation from smooth muscle into striated muscle phenotype. The surgical specimens of 5 rare cases of uterine leiomyosarcoma with a rhabdomyosarcomatous component were formalin fixed and paraffin embedded. In addition to hematoxylin/eosin stains, phosphotungstic acid hematoxylin staining, immunohistochemistry, and methylation-specific polymerase chain reaction the CDKN2A promoter region were performed. Leiomyosarcomatous cells were found to be strongly immunoreactive for both desmin and alpha-smooth muscle actin. Rhabdomyosarcomatous cells were immunoreactive for sarcomeric actin, desmin, vimentin, CD10, and p16. The methylation-specific polymerase chain reaction revealed the presence of a methylated allele and an unmethylated allele in the microdissected samples, coming from leiomyosarcomatous cells. On the contrary, 2 unmethylated alleles, molecular expression of a loss of heterozygosity, were detected in all the microdissected samples in the rhabdomyosarcomatous cells. The loss of heterozygosity methylation in the promoter region of the CDKN2A gene, occurred only in the rhabdomyosarcomatous cells with increases in both p16 and p14 expression. This event may result in an inhibition of cdk4/cdk6 activity, stabilizes the tumor suppressor protein p53, and coincides with the transdifferentiation from smooth muscle into striated muscle. PMID- 27276113 TI - RING domain is essential for the antiviral activity of TRIM25 from orange spotted grouper. AB - Tripartite motif-containing 25 (TRIM25) has been demonstrated to exert crucial roles in the regulation of innate immune signaling. However, the roles of fish TRIM25 in antiviral immune response still remained uncertain. Here, a novel fish TRIM25 gene from orange spotted grouper (EcTRIM25) was cloned and its roles in grouper virus infection were elucidated. EcTRIM25 encoded a 734-aa protein which shared 68% identity to large yellow croaker (Larimichthys crocea). Amino acid alignment showed that EcTRIM25 contained three conserved domains, including a RING-finger domain, a B box/coiled-coil domain and a SPRY domain. In healthy grouper, the transcript of EcTRIM25 was predominantly detected in skin, spleen and intestine. After stimulation with Singapore grouper iridovirus (SGIV) or poly I:C, the relative expression of EcTRIM25 in grouper spleen was significantly increased at the early stage of injection. Subcellular localization analysis showed that EcTRIM25 distributed throughout the cytoplasm in grouper cells. Notably, the deletion RING domain affected its accurate localization and displayed microtubule like structures or bright aggregates in GS cells. After incubation with SGIV or red spotted grouper nervous necrosis virus (RGNNV), overexpression of full length of EcTRIM25 in vitro significantly decreased the viral gene transcription of SGIV and RGNNV. Consistently, the deletion of RING domain obviously affected the inhibitory effect of EcTRIM25. Furthermore, overexpression of EcTRIM25 significantly increased the expression level of interferon related signaling molecules, including interferon regulatory factor (IRF) 3, interferon-induced 35-kDa protein (IFP35), MXI, IRF7 and myeloid differentiation factor 88 (MyD88), suggesting that the positive regulation of interferon immune response by EcTRIM25 might affected RGNNV replication directly. Meanwhile, the expression levels of pro-inflammation cytokines were differently regulated by the ectopic expression of EcTRIM25. We proposed that the regulation of IRF7, MyD88 and pro-inflammation cytokines might contribute more important roles in SGIV infection. In addition, the RING domain of EcTRIM25 also played critical roles in the regulation of interferon immune and inflammation response. Together, our results will provide new evidences that the RING domain was essential for the antiviral action of fish TRIM25 against iridovirus and nodavirus infection. PMID- 27276114 TI - Transcriptome analysis of immune response genes induced by pathogen agonists in the Antarctic bullhead notothen Notothenia coriiceps. AB - Fish are a representative population of lower vertebrates that serve as an essential link to early vertebrate evolution, and this has fueled academic interest in studying ancient vertebrate immune defense mechanisms in teleosts. Notothenia coriiceps, a typical Antarctic notothenioid teleost, has evolved to adapt to the cold and thermally stable Antarctic sea. In this study, we examined adaptive signaling pathways and immune responses to bacterial and viral pathogenic exposure in N. coriiceps. Using RNA sequencing, we investigated transcriptional differences in the liver tissues of N. coriiceps challenged with two pathogen-mimicking agonists, a bacterial ligand (heat-killed Escherichia coli, HKEB) and a viral ligand (polyinosinic:polycytidylic acid, Poly I:C). We found that 567 unique genes were up-regulated two-fold in the HKEB-exposed group, whereas 392 unique genes, including 124 immune-relevant genes, were up-regulated two-fold in the Poly I:C-exposed group. A KEGG pathway analysis of the 124 immune relevant genes revealed that they exhibited major features of antigen processing and presentation bacterial ligand exposure, but they were down-regulated after viral ligand exposure. A quantitative real time RT-PCR analysis revealed that TNFalpha and TNF2, major inducers of apoptosis, were highly up-regulated after exposure to the viral ligand but not the bacterial ligand. The results suggest that the bacterial and viral ligands up-regulate inducers of different immune mechanisms in N. coriiceps liver tissue. N. coriiceps has an immune response defense strategy that uses antigen presentation against bacterial infection, but it may use a different defense, such as TNF-mediated apoptosis, against viral infection. The specific immune responses of N. coriiceps may be adaptations to the Antarctic environment and pathogens. These results will help define the characteristics of Antarctic fish and increase our understanding of their immune response mechanisms. PMID- 27276116 TI - Formation and Self-assembly of Gold Nanoplates through an Interfacial Reaction for Surface-Enhanced Raman Scattering. AB - 3D hierarchical architectures assembled from individual particles have attracted great interest because they displayed novel properties from the individual building blocks as well as their complex structures. Here we present a new strategy to form 3D hierarchical gold (Au) nanostructures via an interfacial reduction reaction. An aniline (ANI) derivative, N-(3-amidino)-aniline (NAAN), and HAuCl4 were separately dissolved in toluene and water to form an organic/water interface. Au nanoplates formed at the interface and subsequently moved to the aqueous phase. As a capping agent for the nanoplate formation, the oxidized NAAN, i.e., poly(N-(3-amidino)-aniline) (PNAAN), also facilitated the self-assembly of Au nanoplates into 3D hierarchical Au nanoflowers (AuNFs) through pi-pi stacking. The individual AuNF exhibited good surface-enhanced Raman scattering (SERS) response both in enhancement factor and reproducibility because it integrates the SERS enhancement effects of individual Au nanoplates and their hierarchical structures. This is the first report depicting the one-pot formation and self-assembly of Au nanoplates into 3D organized hierarchical nanostructures through the molecular interaction of conducting polymer. PMID- 27276115 TI - Minichromosome maintenance protein 7 regulates phagocytosis in kuruma shrimp Marsupenaeus japonicas against white spot syndrome virus. AB - Minichromosome maintenance protein (MCM7) belongs to the MCM protein family and participates in the MCM complex by playing a role in the cell replication cycle and chromosome initiation of eukaryotes. Previously, we found that several genes, including MCM7, were over-expressed in Drosophila melanogaster after white spot syndrome virus (WSSV) infection. In this study, we aimed to further research the MCM7 of kuruma shrimp, Marsupenaeus japonicus (mjMCM7) and determine its role in the innate immune system. To this end, we cloned the entire 2307-bp mjMCM7 sequence, including a 1974-bp open reading frame (ORF) encoding a 658-aa-long protein. Real-time PCR showed that the gene was primarily expressed in the hemolymph and hepatopancreas and over-expressed in shrimp challenged with WSSV. Gene function study was carried out by knocking down the expression of MCM7 using small interference RNA (siRNA). The results revealed that beta-actin, hemocyanin, prophenoloxidase (proPO) and tumor necrosis factor-alpha (TNF-alpha) were up regulated while the cytoskeleton proteins such as myosin and Rho were significantly down-regulated at 24 h after treatment. The results indicate a possible relationship between mjMCM7 and the innate immune system, and suggest that mjMCM7 may play a role in phagocytosis. After WSSV challenge, WSSV copies and mortality count were both higher in the MCM7-siRNA-treated groups at 60 h after treatment, and the mortality count approached that of the control groups over time. The phagocytosis rate was significantly lower in the MCM7-siRNA treated group than in the WSSV group. The findings of this study confirm that mjMCM7 positively regulates phagocytosis and plays an important role against WSSV. These results could help researchers to further understand the function of the MCM7 protein and reveal its potential role in the innate immunity of invertebrates. PMID- 27276117 TI - Predicting preschool pain-related anticipatory distress: the relative contribution of longitudinal and concurrent factors. AB - Anticipatory distress prior to a painful medical procedure can lead to negative sequelae including heightened pain experiences, avoidance of future medical procedures, and potential noncompliance with preventative health care, such as vaccinations. Few studies have examined the longitudinal and concurrent predictors of pain-related anticipatory distress. This article consists of 2 companion studies to examine both the longitudinal factors from infancy as well as concurrent factors from preschool that predict pain-related anticipatory distress at the preschool age. Study 1 examined how well preschool pain-related anticipatory distress was predicted by infant pain response at 2, 4, 6, and 12 months of age. In study 2, using a developmental psychopathology framework, longitudinal analyses examined the predisposing, precipitating, perpetuating, and present factors that led to the development of anticipatory distress during routine preschool vaccinations. A sample of 202 caregiver-child dyads was observed during their infant and preschool vaccinations (the Opportunities to Understand Childhood Hurt cohort) and was used for both studies. In study 1, pain response during infancy was not found to significantly predict pain-related anticipatory distress at preschool. In study 2, a strong explanatory model was created whereby 40% of the variance in preschool anticipatory distress was explained. Parental behaviours from infancy and preschool were the strongest predictors of child anticipatory distress at preschool. Child age positively predicted child anticipatory distress. This strongly suggests that the involvement of parents in pain management interventions during immunization is one of the most critical factors in predicting anticipatory distress to the preschool vaccination. PMID- 27276118 TI - Diagnostic Quality of Magnetic Resonance Imaging Interpretation for Peripheral Nerve Sheath Tumors: Can Malignancy Be Determined? AB - Background Optimal management of peripheral nerve sheath tumors including neurofibromas, schwannomas, and malignant peripheral sheath tumors (MPNSTs) is predicated on knowing the specific pathology. Magnetic resonance imagining (MRI) has the potential to provide insight in the tumor type, yet imprecision in diagnosis remains. We assessed the accuracy of preoperative imaging diagnoses by comparing them with postoperative histopathologic diagnoses. We specifically focus on erroneous diagnosis of MPNSTs. Methods We reviewed all pathologically confirmed cases of nerve sheath tumors treated at our institution retrospectively from 2007 to 2015. Pre- and postoperative imaging data were reviewed for imaging based diagnosis and compared with postresection pathologic diagnosis. Results The study included 127 patients: 82 diagnosed with neurofibroma, 17 with schwannoma, 24 with MPNST, and 4 with other histology types. A mean age of 40.8 +/- 20.4 years, mean tumor size of 4.3 +/- 3.6 cm, and mean follow-up of 29.1 +/- 21.6 months were recorded. A family history of neurofibromatosis type 1 (NF1) was seen in 58 patients (46%). A discordant diagnosis from preoperative imaging and postoperative pathology was found in 65 individuals (51%). Most discordant diagnoses (n = 34) were inconclusive interpretation of preoperative imaging; however, 10 patients were diagnosed with a benign or unknown lesion on preoperative imaging but had an MPNST on histopathology. Patients with MPNST were more likely than those with benign pathologies to have larger lesions (7.6 +/- 4.8 cm versus 3.5 +/- 3.3 cm; p = 0.004); however, a statistically acceptable threshold value could not be found to separate benign from malignant lesions. Clinical factors, such as NF1 status, did not meaningfully improve preoperative diagnosis. Conclusions These results suggest that routine MRI is insufficient to guide surgical decision making reliably. Additional imaging techniques may be necessary to delineate the radiologic features of nerve sheath tumors to determine pathology more precisely. PMID- 27276119 TI - Clinical and Radiographic Results of Indirect Decompression and Posterior Cervical Fusion for Single-Level Cervical Radiculopathy Using an Expandable Implant with 2-Year Follow-Up. AB - Background Indirect posterior cervical nerve root decompression and fusion performed by placing bilateral posterior cervical cages in the facet joints from a posterior approach has been proposed as an option to treat select patients with cervical radiculopathy. The purpose of this study was to report 2-year clinical and radiologic results of this treatment method. Methods Patients who failed nonsurgical management for single-level cervical radiculopathy were recruited. Surgical treatment involved a posterior approach with decortication of the lateral mass and facet joint at the treated level followed by placement of the DTRAX Expandable Cage (Providence Medical Technology, Lafayette, California, United States) into both facet joints. Iliac crest bone autograft was mixed with demineralized bone matrix and used in all cases. The Neck Disability Index (NDI), visual analog scale (VAS) for neck and arm pain, and SF-12 v.2 questionnaire were evaluated preoperatively and 2 years postoperatively. Segmental (treated level) and overall C2-C7 cervical lordosis, disk height, adjacent segment degeneration, and fusion were assessed on computed tomography scans and radiographs acquired preoperatively and 2 years postoperatively. Results Overall, 53 of 60 enrolled patients were available at 2-year follow-up. There were 35 females and 18 males with a mean age of 53 years (range: 40-75 years). The operated level was C3-C4 (N = 3), C4-C5 (N = 6), C5-C6 (N = 36), and C6-C7 (N = 8). The mean preoperative and 2-year scores were NDI: 32.3 versus 9.1 (p < 0.0001); VAS Neck Pain: 7.4 versus 2.6 (p < 0.0001); VAS Arm Pain: 7.4 versus 2.6 (p < 0.0001); SF-12 Physical Component Summary: 34.6 versus 43.6 (p < 0.0001), and SF-12 Mental Component Summary: 40.8 versus 51.4 (p < 0.0001). No significant changes in overall or segmental lordosis were noted after surgery. Radiographic fusion rate was 98.1%. There was no device failure, implant lucency, or surgical reinterventions. Conclusions Indirect decompression and posterior cervical fusion using an expandable intervertebral cage may be an effective tissue-sparing option in select patients with single-level cervical radiculopathy. PMID- 27276120 TI - Socioeconomic Drivers of Greenhouse Gas Emissions in the United States. AB - Existing studies examined the U.S.'s direct GHG emitters and final consumers driving upstream GHG emissions, but overlooked the U.S.'s primary suppliers enabling downstream GHG emissions and relative contributions of socioeconomic factors to GHG emission changes from the supply side. This study investigates GHG emissions of sectors in the U.S. from production-based (direct emissions), consumption-based (upstream emissions driven by final consumption of products), and income-based (downstream emissions enabled by primary inputs of sectors) viewpoints. We also quantify relative contributions of socioeconomic factors to the US's GHG emission changes during 1995-2009 from both the consumption and supply sides, using structural decomposition analysis (SDA). Results show that income-based method can identify new critical sectors leading to GHG emissions (e.g., Renting of Machinery & Equipment and Other Business Activities and Financial Intermediation sectors) which are unidentifiable by production-based and consumption-based methods. Moreover, the supply side SDA reveals new factors for GHG emission changes: mainly production output structure representing product allocation pattern and primary input structure indicating sectoral shares in primary inputs. In addition to production-side and consumption-side GHG reduction measures, the U.S. should also pay attention to supply side measures such as influencing the behaviors of product allocation and primary inputs. PMID- 27276162 TI - The Effects of Trauma History and Prenatal Affective Symptoms on Obstetric Outcomes. AB - Prenatal maternal mood may inform the adverse obstetric outcomes seen in disadvantaged populations. The contribution of having a trauma history is not well studied. We examined the impact of trauma exposure and mood symptoms on obstetric outcomes in 358 women. Women with antecedent trauma were more likely to have a history of depression, odds ratio = 2.83, 95% confidence interval [1.81, 4.42], were younger at their first pregnancy, 18.86 years versus 20.10 years, and had a higher number of previous pregnancies, 2.01 versus 1.54, compared to those with no trauma exposure. Women with prenatal anxiety had significantly smaller babies than nonanxious women, 3,313.17 g, (SD = 441.58) versus 3,429.27 g, (SD = 437.82) Trauma history magnified the effects of maternal prenatal mood on birthweight; the moderating effect was limited to those who first experienced a trauma under 18 years of age. Childhood trauma exposure increased vulnerability for low birthweight delivery associated with prenatal mood disturbance. Screening pregnant women for trauma history and current mood symptoms is indicated. PMID- 27276163 TI - Competitive immobilization of Pb in an aqueous ternary-metals system by soluble phosphates with varying pH. AB - Chemical immobilization by phosphates has been widely and successfully applied to treat Pb in wastewater and contaminated soils. Pb in wastewaters and soils, however, always coexists with other heavy metals and their competitive reactions with phosphates have not been quantitatively and systematically studied. In this approach, immobilization of Pb, Zn, and Cd by mono-, di-, and tripotassium phosphate (KH2PO4, K2HPO4, and K3PO4) was observed in the single- and ternary metals solutions. The immobilization rates of the three metals were determined by the residual concentration. The mineral composition and structure of the precipitates were characterized by powder X-ray diffraction (XRD) analysis and scanning electron microscopy (SEM). The results indicated that competitive reaction occurred in Pb-Zn-Cd ternary system, with immobilization rates decrease of <3.6%, <78%, and <89% for Pb, Zn and Cd (molar ratios of P: metal <1), respectively, compared to single metal system. The reaction of Pb with three phosphates exhibited intense competitiveness and the phosphates had a stronger affinity for Pb when Cl(-) was added. Pb-phosphate minerals formed by KH2PO4 with the better crystalline characteristics and largest size were very stable with a low dissolution rate (<0.02%) in the solution of pH 2.88, compared to K2HPO4 and K3PO4. This study demonstrated that Pb could be firstly and effectively immobilized by phosphates in multi-metal solutions containing Pb, Zn and Cd. Moreover, the research provided the insight of the importance of phosphate with low pH (e.g. KH2PO4) and the presence of Cl(-) for more efficient immobilization of Pb in the multi-metals pollution system. PMID- 27276164 TI - Effect of humic substances aggregation on the determination of fluoride in water using an ion selective electrode. AB - The control of drinking water quality is critical in preventing fluorosis. In this study humic substances (HS) are considered as representative of natural organic matter (NOM) in water. We show that when HS aggregate the response of fluoride ion selective electrodes (ISE) may be perturbed. Dynamic light scattering (DLS) results of both synthetic solutions and natural water sample suggest that low pH and high ionic strength induce HS aggregation. In the presence of HS aggregates, fluoride concentration measured by ISE has a reduction up to 19%. A new "open cage" concept has been developed to explain this reversible phenomenon. The interference of HS aggregation on fluoride measurement can be effectively removed by centrifugation pretreatment. PMID- 27276165 TI - Effects of kinesiotaping versus non-steroidal anti-inflammatory drugs and physical therapy for treatment of pes anserinus tendino-bursitis: A randomized comparative clinical trial. AB - OBJECTIVE: Pes anserinus tendino-bursitis is a condition caused by repetitive friction over the bursa or direct trauma to knee joint and it presents with proximal medial tibial pain and swelling. The aim of this study is to determine the effects of kinesiotaping in comparison with naproxen and physical therapy in treatment of pes anserinus tendino-bursitis. METHODS: In a randomized comparative clinical trial 56 patients with clinical diagnosis of pes anserinus tendino bursitis were randomly assigned to kinesiotaping and naproxen/physical therapy (28 patients in each group). Kinesiotaping on the tender area in the form of space-correction (lifting) technique was used and repeated for three times with a one-week interval. Another group received naproxen (250mg TID for 10 days) and ten sessions of daily physical therapy. The visual analog scale (VAS) was used for evaluation of pain. The depth of swelling of the area was measured with sonography before and after treatment. Wilcoxon signed ranks test has been used for determining the influence of interventions on pain (VAS) and swelling scores in each group. The ANCOVA (Analysis of covariance) test was applied for comparing the influence of interventions on VAS and swelling scores after adjustment for co variables. RESULTS: At end of the study, 27 patients remained in the kinesiotaping group and 19 patients in naproxen/physical therapy group. Treatment with kinesiotaping significantly decreased the pain (P=0.0001) and swelling scores (P=0.0001) in comparison with naproxen/physical therapy after adjustment for baseline characteristics. Kinesiotaping was safe without any complications except for a mild local skin irritation in one patient. CONCLUSION: Kinesiotaping is more effective than naproxen plus physical therapy in reduction of pain and swelling in patients with pes anserinus tendino-bursitis. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov identifier is NCT01680263. PMID- 27276167 TI - Tuning Light Emission of a Pressure-Sensitive Silicon/ZnO Nanowires Heterostructure Matrix through Piezo-phototronic Effects. AB - Based on white light emission at silicon (Si)/ZnO hetrerojunction, a pressure sensitive Si/ZnO nanowires heterostructure matrix light emitting diode (LED) array is developed. The light emission intensity of a single heterostructure LED is tuned by external strain: when the applied stress keeps increasing, the emission intensity first increases and then decreases with a maximum value at a compressive strain of 0.15-0.2%. This result is attributed to the piezo phototronic effect, which can efficiently modulate the LED emission intensity by utilizing the strain-induced piezo-polarization charges. It could tune the energy band diagrams at the junction area and regulate the optoelectronic processes such as charge carriers generation, separation, recombination, and transport. This study achieves tuning silicon based devices through piezo-phototronic effect. PMID- 27276166 TI - Differentiation of Human Mesenchymal Stem Cells Toward Quality Cartilage Using Fibrinogen-Based Nanofibers. AB - Mimicking the complex intricacies of the extra cellular matrix including 3D configurations and aligned fibrous structures were traditionally perused for producing cartilage tissue from stem cells. This study shows that human adipose derived mesenchymal stem cells (hADMSCs) establishes significant chondrogenic differentiation and may generate quality cartilage when cultured on 2D and randomly oriented fibrinogen/poly-lactic acid nanofibers compared to 3D sandwich like environments. The adhering cells show well-developed focal adhesion complexes and actin cytoskeleton arrangements confirming the proper cellular interaction with either random or aligned nanofibers. However, quantitative reverse transcription-polymerase chain reaction analysis for Collagen 2 and Collagen 10 genes expression confirms favorable chondrogenic response of hADMSCs on random nanofibers and shows substantially higher efficacy of their differentiation in 2D configuration versus 3D constructs. These findings introduce a new direction for cartilage tissue engineering through providing a simple platform for the routine generation of transplantable stem cells derived articular cartilage replacement that might improve joint function. PMID- 27276168 TI - Predictive ability of the pooled cohort risk assessment for the incidence and progression of coronary artery calcification. AB - OBJECTIVE: The aim of the present study was to evaluate the predictive ability of pooled cohort risk assessment (PRA) models for the incidence and progression of coronary artery calcification (CAC) over time comparing the Framingham risk score (FRS) in a healthy Korean population. METHODS: The study cohort included 4194 individuals, aged 40 or older, without a history of cardiovascular disease or statin therapy, who underwent repeated cardiac computed tomography for CAC scoring from 2011 to 2014. Logistic regression models and Cox proportional hazards models were used. RESULTS: Of the 4194 individuals, 1244 had CAC progression and during over 5184 person-years of follow-up, 204 participants developed incident CAC. Compared with patients whose FRS was less than 10%, the odds ratios (ORs) [95% confidence intervals (CIs)] for CAC progression in patients whose FRS ranged from 10 to 20% and whose FRS was at least 20% were 2.54 (2.17-2.98) and 3.73 (2.69-5.15), respectively. Similarly, compared with the reference group, whose PRA was less than 5%, the ORs (95% CIs) for CAC progression in patients whose PRAs ranged from 5 to less than 7.5%, 7.5 to less than 10%, and at least 10% were 1.85 (95% CI 1.52-2.25), 2.63 (95% CI 2.01-3.46), and 3.58 (95% CI 2.73-4.70), respectively. Similarly, both PRA and FRS were associated positively with the development of CAC in a dose-response manner. In discriminating incident CAC and progression using receiver operating characteristic analysis, PRA was not significantly different from FRS. CONCLUSION: In a large sample of asymptomatic Korean adults without cardiovascular disease, both the PRA and FRS similarly predict the onset and progression of subclinical atherosclerosis over time. PMID- 27276169 TI - Ferrocenyl Quinone Methide-Thiol Adducts as New Antiproliferative Agents: Synthesis, Metabolic Formation from Ferrociphenols, and Oxidative Transformation. AB - Ferrociphenols (FCs) and their oxidized, electrophilic quinone methide metabolites (FC-QMs) are organometallic compounds related to tamoxifen that exhibit strong antiproliferative properties. To evaluate the reactivity of FC-QMs toward cellular nucleophiles, we studied their reaction with selected thiols. A series of new compounds resulting from the addition of these nucleophiles, the FC SR adducts, were thus synthesized and completely characterized. Such conjugates are formed upon metabolism of FCs by liver microsomes in the presence of NADPH and thiols. Some of the FC-SR adducts exhibit antiproliferative properties comparable to those of their FC precursors. Under oxidizing conditions they either revert to their FC-QM precursors or transform into new quinone methides (QMs) containing the SR moiety, FC-SR-QM. These results provide interesting data about the reactivity and mechanism of antiproliferative effects of FCs, and also open the way to a new series of organometallic antitumor compounds. PMID- 27276170 TI - HIV Incidence Estimates Using the Limiting Antigen Avidity EIA Assay at Testing Sites in Kiev City, Ukraine: 2013-2014. AB - OBJECTIVE: To estimate HIV incidence and highlight the characteristics of persons at greatest risk of HIV in the Ukraine capital, Kiev. METHOD: Residual samples from newly-diagnosed persons attending the Kiev City AIDS Centre were tested for evidence of recent HIV infection using an avidity assay. Questions on possible risk factors for HIV acquisition and testing history were introduced. All persons (>=16yrs) presenting for an HIV test April'13-March'14 were included. Rates per 100,000 population were calculated using region-specific denominators. RESULTS: During the study period 6370 individuals tested for HIV. Of the 467 individuals newly-diagnosed with HIV, 21 had insufficient samples for LAg testing. Of the remaining 446, 39 (8.7%) were classified as recent with an avidity index <1.5ODn, 10 were reclassified as long-standing as their viral load was <1000 copies/mL, resulting in 29 (6.5%) recent HIV infections. The only independent predictor for a recent infection was probable route of exposure, with MSM more likely to present with a recent infection compared with heterosexual contact [Odds Ratio 8.86; 95%CI 2.65-29.60]. We estimated HIV incidence at 21.5 per 100,000 population, corresponding to 466 new infections. Using population estimates for MSM and PWID, incidence was estimated to be between 2289.6 and 6868.7/100,000 MSM, and 350.4 for PWID. CONCLUSION: A high proportion of persons newly-infected remain undiagnosed, with MSM disproportionally affected with one in four newly HIV-diagnosed and one in three recently-HIV-infected. Our findings should be used for targeted public health interventions and health promotion. PMID- 27276171 TI - Photocatalytic Reduction of CO2 over Heterostructure Semiconductors into Value Added Chemicals. AB - Photoreduction of CO2 , which utilizes solar energy to convert CO2 into hydrocarbons, can be an effective means to overcome the increasing energy crisis and mitigate the rising emissions of greenhouse gas. This article covers recent advances in the CO2 photoreduction over heterostructure-based photocatalysts. The fundamentals of CO2 photoreduction and classification of the heterostructured photocatalysts are discussed first, followed by the latest work on the CO2 photoreduction over heterostructured photocatalysts in terms of the classification of the coupling semiconductors. Finally, a brief summary and a perspective on the challenges in this area are presented. PMID- 27276172 TI - [Impact of Morbidity on Health Care Costs of a Department of Health through Clinical Risk Groups. Valencian Community, Spain]. AB - BACKGROUND: Risk adjustment systems based on diagnosis stratify the population according to the observed morbidity. The aim of this study was to analyze the total health expenditure in a health area, relating to age, gender and morbidity observed in the population. METHODS: Observational cross-sectional study of population and area of health care costs in the Health District of Denia-Marina Salud (Alicante) in 2013. Population (N=156,811) were stratified by Clinical Risk Groups into 9 states of health, state 1 being healthy, and state 9 the highest disease burden. Each inhabitant was charged with the hospital costs, primary care and outpatient pharmacy to obtain the total costs. Health status and severity by age and gender, as well as the costs of each group were analysed. The statistical tests, student t and chi2 were applied to verify the existence of significant differences between and intra groups. RESULTS: The average cost per inhabitant was 983 euros which increased from 240 euros to 42,881 at the state 9 and severity level 6. Patients of health states 5 and 6 caused the largest expenditure by concentration of the population, but health states 8 and 9 had the highest average expenditure, with 80% of hospitalised cost. CONCLUSIONS: A different composition of health expenditure per individual morbidity was corroborated, with an exponential growth in hospital spending. PMID- 27276173 TI - NMR Backbone Assignment of Large Proteins by Using (13) Calpha -Only Triple Resonance Experiments. AB - Nuclear magnetic resonance (NMR) is a powerful tool to interrogate protein structure and dynamics residue by residue. However, the prerequisite chemical shift assignment remains a bottleneck for large proteins due to the fast relaxation and the frequency degeneracy of the (13) Calpha nuclei. Herein, we present a covariance NMR strategy to assign the backbone chemical shifts by using only HN(CO)CA and HNCA spectra that has a high sensitivity even for large proteins. By using the peak linear correlation coefficient (LCC), which is a sensitive probe even for tiny chemical-shift displacements, we correctly identify the fidelity of approximately 92 % cross-peaks in the covariance spectrum, which is thus a significant improvement on the approach developed by Snyder and Bruschweiler (66 %) and the use of spectral derivatives (50 %). Thus, we calculate the 4D covariance spectrum from HN(CO)CA and HNCA experiments, in which cross-peaks with LCCs above a universal threshold are considered as true correlations. This 4D covariance spectrum enables the sequential assignment of a 42 kDa maltose binding protein (MBP), in which about 95 % residues are successfully assigned with a high accuracy of 98 %. Our LCC approach, therefore, paves the way for a residue-by-residue study of the backbone structure and dynamics of large proteins. PMID- 27276174 TI - Low-haze, annealing-free, very long Ag nanowire synthesis and its application in a flexible transparent touch panel. AB - Since transparent conducting films based on silver nanowires (AgNWs) have shown higher transmittance and electrical conductivity compared to those of indium tin oxide (ITO) films, the electronics industry has recognized them as promising substitutes. However, due to the higher haze value of AgNW transparent conducting films compared to ITO films, the clarity is decreased when AgNW films are applied to optoelectronic devices. In this study, we develop a highly transparent, low haze, very long AgNW percolation network. Moreover, we confirm that analyzed chemical roles can easily be applied to different AgNW synthesis methods, and that they have a direct impact on the nanowire shape. Consequently, the lengths of the wires are increased up to 200 MUm and the diameters of the wires are decreased up to 45 nm. Using these results, we fabricate highly transparent (96%) conductors (100 Omega/sq) with low-haze (2%) without any annealing process. This electrode shows enhanced clarity compared to previous results due to the decreased diffusive transmittance and scattering. In addition, a flexible touchscreen using a AgNW network is demonstrated to show the performance of modified AgNWs. PMID- 27276175 TI - How and why does the pharmaceutical management of PTSD differ between men and women? PMID- 27276176 TI - DNA nanovehicles and the biological barriers. AB - DNA is emerging as a smart material to construct nanovehicles for targeted drug delivery. The programmability of Watson-Crick base paring enables construction of defined and dynamic DNA nanostructures of almost arbitrary shape and DNA can readily be functionalized with a variety of molecular modules. The applications of DNA nanostructures are still in its infancy, but one of the high expectations are to deliver solutions for targeted therapy. Nucleic acids, however, do not easily enter cells unassisted and biological barriers and harsh nucleolytic conditions in the human body must also be overcome. Here, we highlight recent strategies for DNA nanostructures in drug delivery, DNA nanovehicles, to facilitate targeting and crossing of the biological barriers. In light of this, we discuss future solutions and challenges for DNA nanovehicles to unravel their great potential to facilitate targeted drug delivery. PMID- 27276178 TI - Intensive Care Unit Admission and Death Rates of Infants Admitted With Respiratory Syncytial Virus Lower Respiratory Tract Infection in Mexico. AB - BACKGROUND: Respiratory syncytial virus (RSV) is the most common etiology for acute respiratory infection hospital admissions in young children. Case fatality rates for hospitalized patients range between 0% and 3.4%. Recent reports indicate that deaths associated with RSV are uncommon in developed countries. However, the role of this virus as a current cause of mortality in other countries requires further examination. METHODS: Children with RSV infection admitted between May 2003 and December 2014 to a level 2 specialty hospital in Mexico were included in this analysis. Underlying risk factors, admission to the intensive care unit (ICU) and condition on discharge were assessed to determine the ICU admission and death rates associated to RSV infection. RESULTS: We analyzed data of 1153 patients with RSV infection in whom information regarding underlying illnesses and discharge status was available. Sixty patients (5.2 %) were admitted to the ICU and 12 (1.04 %) died. Relevant underlying conditions were present in 320 (27.7%) patients. Infants with underlying respiratory disorders (excluding asthma) and a history of prematurity had high ICU admission rates (17.1% and 13.8%, respectively). Mortality rates were highest for infants with respiratory disease (excluding asthma) (7.3%), cardiovascular diseases (5.9%) and neurologic disorders (5.3%). The ICU admission and death rates were higher in infants <6 months of age than in other age groups. CONCLUSIONS: The ICU admission rate and mortality rate in Mexican infants hospitalized with RSV infection were 5.2% and 1%, respectively. Mortality rates were high in infants with respiratory, cardiovascular and neurologic disorders. PMID- 27276179 TI - Pharmacokinetics of Colistin Following a Single Dose of Intravenous Colistimethate Sodium in Critically Ill Neonates. AB - In this study, we sought to evaluate the pharmacokinetics of colistin after intravenous administration of colistimethate sodium (CMS) in the critically ill neonates with Gram-negative bacterial infections. A single intravenous dose of CMS [approximately 150,000 IU/kg, equivalent to 5 mg/kg colistin base activity (CBA)] was administered to 7 critically ill neonates. Mean (+/-SD) maximum plasma colistin concentration and area under the time-concentration curve from 0 to infinity were 3.0 +/- 0.7 ug/mL and 25.3 +/- 10.4 ug.h/mL, respectively. Time to maximum concentration, half-life, apparent volume of distribution and clearance were 1.3 +/- 0.9 hours, 9.0 +/- 6.5 hours, 7.7 +/- 9.3 L/kg and 0.6 +/- 0.3 L/h/kg, respectively. After a dose regimen of 5 mg/kg CBA every 24 hours, the average concentration expected at steady state is 1.1 +/- 0.4 ug/mL. In critically ill neonates, a single intravenous dose of 5 mg CBA/kg (approximately 150,000 IU/kg of CMS) resulted in suboptimal plasma concentrations of colistin. According to our pharmacokinetics data, the dosage of CMS currently used in critically ill neonates is insufficient. PMID- 27276177 TI - Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics. AB - BACKGROUND: Twenty-five percent to 50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. METHODS: Two hundred ninety seven children <=6 years of age, admitted to hospital in Slovenia, October 2011 to October 2012, with AGE, and 88 <=6 years old healthy children were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. RESULTS: At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing, and a potential viral pathogen was detected in 17 additional samples (5.8%). CONCLUSIONS: Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens. PMID- 27276180 TI - Nonlinear and Interactive Effects of Temperature and Humidity on Childhood Hand, Foot and Mouth Disease in Hefei, China. AB - BACKGROUND: Hand, foot and mouth disease (HFMD) is one of the major infectious diseases among children and remains a health threat, especially among Asian countries. Many epidemiologic studies suggested significant association of air temperature and humidity with childhood HFMD; however, evidence on the temperature effects on childhood HFMD in temperate cities is limited, and the interactive effects of temperature and humidity have not been studied yet. METHODS: Daily counts of HFMD in children younger than 15 years of age and daily meteorologic variables during 2010 to 2012 were obtained in Hefei, China. A distributed lag nonlinear model was applied to estimate the potential nonlinear association between temperature and childhood HFMD. The interactive effects between temperature and humidity on childhood HFMD were also investigated. RESULTS: Temperature rise was associated with higher risk of childhood HFMD. Within the incubation period of HFMD, temperature rise appeared to have the acute effects on childhood HFMD, and a 5 degrees C increase of temperature at lag 0-6 days was associated with 24.8% (95% confidence interval: 11.94%-39.10%) increase of childhood HFMD. Females and children of 0-4 years of agewere more vulnerable to temperature rise. Notably, there were obvious combined effects between temperature and humidity on childhood HFMD-the risk of childhood HFMD elevated at higher temperature and humidity level. CONCLUSIONS: This study provides evidence that temperature and humidity may jointly affect childhood HFMD, and such interactive impact needs to be considered when evaluating the temperature childhood HFMD relationship. PMID- 27276181 TI - Risk Factors for Presumed Bacterial Pneumonia Among HIV-uninfected Children Hospitalized in Soweto, South Africa. AB - BACKGROUND: Pneumonia is a leading cause of child morbidity and death. Data on risk factors can guide prevention efforts. Within a study on pneumococcal conjugate vaccine effectiveness, we investigated risk factors for presumed bacterial pneumonia (PBP). METHODS: PBP cases were human immunodeficiency virus (HIV) uninfected children with lower respiratory tract infection and consolidation on chest radiograph or nonconsolidated infiltrate with C-reactive protein >=40 mg/L hospitalized at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto. Age-matched community controls were identified using CHBAH birth records +/-1 week of case birth date. Data were analyzed using conditional logistic regression. RESULTS: A total of 889 PBP cases (median age 9 months) were matched to 2628 controls. Crowding was a significant risk factor among well nourished children (adjusted odds ratio [aOR]: 2.29, 95% confidence interval [CI]: 1.89-2.78), but not in those with low weight-for-age. Malnutrition was associated with PBP; strength of association was highest in the absence of crowding (aOR: 6.68, 95% CI: 4.74-9.42). Exclusive breastfeeding was protective only among HIV-unexposed children (aOR: 0.65, 95% CI: 0.54-0.78). Self-reported maternal HIV infection was a risk factor among children exclusively breastfeed up to 4 months (aOR: 2.33, 95% CI: 1.53-3.55). Having indoor tap water was protective (aOR: 0.65, 95% CI: 0.54-0.78), whereas a primary care giver who smoked was a risk factor (aOR: 5.15, 95% CI: 2.94-9.03). CONCLUSIONS: Our findings confirm several known pneumonia risk factors and highlight complex interactions between factors, including HIV exposure, breastfeeding, malnutrition and crowding. Improved housing, reduced secondhand smoke exposure and HIV prevention among women of reproductive age could lessen the child pneumonia burden. PMID- 27276183 TI - Archaeal lipid vaccine adjuvants for induction of cell-mediated immunity. AB - INTRODUCTION: Liposomal vesicles (archaeosomes) composed of total polar lipids (TPL) or semi-synthetic glycerolipids, unique to the domain Archaea, constitute potent vaccine adjuvant and delivery systems. The characteristics of this adjuvant offer a novel prospect for the development of effective vaccines for emerging infections and cancers, which is reviewed in this article. Areas covered: The areas covered in this review include the chemical composition and physical characteristics, various in-vitro and in-vivo pre-clinical immunogenicity and efficacy studies for systemic immunization, induction of mucosal immunity upon modification of the formulation with cations, and the mechanism of adjuvant action following uptake by antigen presenting cells. Expert commentary: The unique features of archaeal lipids confer archaeosomes with many desirable features. With the use of semi-synthetic archaeosomes, highly defined lipids that are safe and robust for induction of cell-mediated immunity may be chosen. These adjuvants function as Toll-like receptor-independent innate immune stimulants. PMID- 27276185 TI - A real-time reverse transcriptase polymerase chain reaction for detection and quantification of Vesiculovirus. AB - Vesiculoviruses (VSV) are zoonotic viruses that cause vesicular stomatitis disease in cattle, horses and pigs, as well as sporadic human cases of acute febrile illness. Therefore, diagnosis of VSV infections by reliable laboratory techniques is important to allow a proper case management and implementation of strategies for the containment of virus spread. We show here a sensitive and reproducible real-time reverse transcriptase polymerase chain reaction (RT-PCR) for detection and quantification of VSV. The assay was evaluated with arthropods and serum samples obtained from horses, cattle and patients with acute febrile disease. The real-time RT-PCR amplified the Piry, Carajas, Alagoas and Indiana Vesiculovirus at a melting temperature 81.02 +/- 0.8oC, and the sensitivity of assay was estimated in 10 RNA copies/mL to the Piry Vesiculovirus. The viral genome has been detected in samples of horses and cattle, but not detected in human sera or arthropods. Thus, this assay allows a preliminary differential diagnosis of VSV infections. PMID- 27276186 TI - Low impact to fixed cell processing aiming transmission electron microscopy. AB - In cell culture, cell structures suffer strong impact due to centrifugation during processing for electron microscope observation. In order to minimise this effect, a new protocol was successfully developed. Using conventional reagents and equipments, it took over one week, but cell compression was reduced to none or the lowest deformation possible. PMID- 27276187 TI - Magnetic Co@g-C3N4 Core-Shells on rGO Sheets for Momentum Transfer with Catalytic Activity toward Continuous-Flow Hydrogen Generation. AB - Magnetic core-shell structures provide abundant opportunities for the construction of multifunctional composites. In this article, magnetic core-shells were fabricated with Co nanoparticles (NPs) as cores and g-C3N4 as shells. In the fabrication process, the Co@g-C3N4 core-shells were anchored onto the rGO nanosheets to form a Co@g-C3N4-rGO composite (CNG-I). For hydrogen generation from the hydrolysis of NaBH4 or NH3BH3, the Co NP cores act as catalytic active sites. The g-C3N4 shells protect Co NPs cores from aggregating or growing. The connection between Co NPs and rGO was strengthened by the g-C3N4 shells to prevent them from leaching or flowing away. The g-C3N4 shells also work as a cocatalyst for hydrogen generation. The magnetism of Co NPs and the shape of rGO nanosheets achieve effective momentum transfer in the external magnetic field. In the batch reactor, a higher catalytic activity was obtained for CNG-I in self stirring mode than in magneton stirring mode. In the continuous-flow process, stable hydrogen generation was carried out with CNG-I being fixed and propelled by the external magnetic field. The separation film is unnecessary because of magnetic momentum transfer. This idea of the composite design and magnetic momentum transfer will be useful for the development of both hydrogen generation and multifunctional composite materials. PMID- 27276184 TI - Pathogenicity and phenotypic sulfadiazine resistance of Toxoplasma gondii isolates obtained from livestock in northeastern Brazil. AB - Toxoplasma gondii is the causative protozoan agent of toxoplasmosis, which is a common infection that is widely distributed worldwide. Studies revealed stronger clonal strains in North America and Europe and genetic diversity in South American strains. Our study aimed to differentiate the pathogenicity and sulfadiazine resistance of three T. gondii isolates obtained from livestock intended for human consumption. The cytopathic effects of the T. gondii isolates were evaluated. The pathogenicity was determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) using a CS3 marker and in a rodent model in vivo. Phenotypic sulfadiazine resistance was measured using a kinetic curve of drug activity in Swiss mice. IgM and IgG were measured by ELISA, and the dihydropteroate synthase (DHPS) gene sequence was analysed. The cytopathic effects and the PCR-RFLP profiles from chickens indicated a different infection source. The Ck3 isolate displayed more cytopathic effects in vitro than the Ck2 and ME49 strains. Additionally, the Ck2 isolate induced a differential humoral immune response compared to ME49. The Ck3 and Pg1 isolates, but not the Ck2 isolate, showed sulfadiazine resistance in the sensitivity assay. We did not find any DHPS gene polymorphisms in the mouse samples. These atypical pathogenicity and sulfadiazine resistance profiles were not previously reported and served as a warning to local health authorities. PMID- 27276188 TI - Diffuse Reflectance Spectroscopy Versus Mexameter((r)) MX18 Measurements of Melanin and Erythema in an African Population. AB - Melanin provides protection against excess exposure to solar ultraviolet radiation (UVR) and related adverse health effects. Diffuse reflectance spectroscopy (DRS) can be used to calculate cutaneous melanin and erythema, but this is complex and has been mostly used for light-to-medium pigmented skin. Handheld reflectance spectrophotometers, such as the Mexameter((r)) MX18, can also be used. We compared DRS-calculated melanin and erythema values with Mexameter melanin and erythema index values to understand how these techniques/measurements correlate in an African population of predominantly deeply pigmented skin. Five hundred and three participants comprised 68.5% self identified Black African, 9.9% Indian/Asian, 18.4% White and 2.9% Colored. The majority of Black African (45%), Indian/Asian (34%) and Colored (53%) participants self-identified their skin as being "brown." Measured melanin levels increased with darker self-reported skin color. DRS-calculated and Mexameter melanin values demonstrated a positive correlation (Spearman rho = 0.87, P < 0.001). The results from both instruments showed erythema values were strongly correlated with their own melanin values. This finding is considered spurious and may result from the complexity of separating brown and red pigment when using narrowband reflectance techniques. Further work is needed to understand melanin, erythema and color in Black skin given sun-related health risks in vulnerable groups in Africa. PMID- 27276189 TI - Size- and shape-dependent catalytic performances of oxidation and reduction reactions on nanocatalysts. AB - Heterogeneous catalysis is one of the most important chemical processes of various industries performed on catalyst nanoparticles with different sizes or/and shapes. In the past two decades, the catalytic performances of different catalytic reactions on nanoparticles of metals and oxides with well controlled sizes or shapes have been extensively studied thanks to the spectacular advances in syntheses of nanomaterials of metals and oxides. This review discussed the size and shape effects of catalyst particles on catalytic activity and selectivity of reactions performed at solid-gas or solid-liquid interfaces with a purpose of establishing correlations of size- and shape-dependent chemical and structural factors of surface of a catalyst with the corresponding catalytic performances toward understanding of catalysis at a molecular level. PMID- 27276190 TI - A rare form of limb girdle muscular dystrophy (type 2E) seen in an Iranian family detected by autozygosity mapping. AB - Sarcoglycanopathies (SGPs) constitute a subgroup of autosomal recessive limb girdle muscular dystrophies (LGMDs) which are caused by mutations in sarcoglycan (SGs) genes. SG proteins form a core complex consisting of alpha, beta, gamma and delta sarcoglycans which are encoded by SGCA, SGCB, SGCG and SGCD genes, respectively. Genetic defect, in any of these SG proteins, results in instability of the whole complex. This effect can be helpful in interpreting muscle biopsy results. Autozygosity mapping is a gene mapping approach which can be applied in large consanguineous families for tracking the defective gene in most autosomal recessive disorders. In the present study, we used autozygosity mapping, to find the gene responsible for muscular dystrophy. Proband was a 10-year-old boy referred to our center for ruling out DMD (Duchenne muscular dystrophy). According to the pedigree and clinical reports, we assessed him for SGPs. Haplotyping, using the four short tandem repeat (STR) markers for each of the SG genes, showed that the phenotype may segregate with SGCB gene; and observing two crossing overs which occurred within the gene suggested that the mutation might be in the first two exons of SGCB gene. Mutation analysis showed a 26 bp duplication (10 bp before the initiation codon till 13 bp after the ATG start codon). This will cause a frameshift in protein synthesis. PMID- 27276192 TI - Effects of EPHX1 and CYP3A4*22 genetic polymorphisms on carbamazepine metabolism and drug response among Tunisian epileptic patients. AB - The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A4*22 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A4*22 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism. PMID- 27276193 TI - Effects of transgenic expression of botulinum toxins in Drosophila. AB - Clostridial neurotoxins (botulinum toxins and tetanus toxin) disrupt neurotransmitter release by cleaving neuronal SNARE proteins. We generated transgenic flies allowing for conditional expression of different botulinum toxins and evaluated their potential as tools for the analysis of synaptic and neuronal network function in Drosophila melanogaster by applying biochemical assays and behavioral analysis. On the biochemical level, cleavage assays in cultured Drosophila S2 cells were performed and the cleavage efficiency was assessed via western blot analysis. We found that each botulinum toxin cleaves its Drosophila SNARE substrate but with variable efficiency. To investigate the cleavage efficiency in vivo, we examined lethality, larval peristaltic movements and vision dependent motion behavior of adult Drosophila after tissue-specific conditional botulinum toxin expression. Our results show that botulinum toxin type B and botulinum toxin type C represent effective alternatives to established transgenic effectors, i.e. tetanus toxin, interfering with neuronal and non neuronal cell function in Drosophila and constitute valuable tools for the analysis of synaptic and network function. PMID- 27276191 TI - Dopamine transporter mutant animals: a translational perspective. AB - The dopamine transporter (DAT) plays an important homeostatic role in the control of both the extracellular and intraneuronal concentrations of dopamine, thereby providing effective control over activity of dopaminergic transmission. Since brain dopamine is known to be involved in numerous neuropsychiatric disorders, investigations using mice with genetically altered DAT function and thus intensity of dopamine-mediated signaling have provided numerous insights into the pathology of these disorders and novel pathological mechanisms that could be targeted to provide new therapeutic approaches for these disorders. In this brief overview, we discuss recent investigations involving animals with genetically altered DAT function, particularly focusing on translational studies providing new insights into pathology and pharmacology of dopamine-related disorders. Perspective applications of these and newly developed models of DAT dysfunction are also discussed. PMID- 27276194 TI - Pharmacological evaluation of orexin receptor antagonists in preclinical animal models of pain. AB - Orexin signaling, known to modulate arousal and vigilance, is also involved in nociception as orexin neurons project to regions of the brain and spinal cord involved in pain processing, and the administration of orexin peptides can alter pain response in a wide range of preclinical models. Pharmacological treatment with the potent, selective and structurally distinct dual orexin receptor antagonists (ORAs) DORA-12 and DORA-2 significantly reduced pain responses during both phases I and II of the mouse formalin pain model and significantly reversed hyperalgesia in the rat complete Freund's adjuvant pain model, respectively. Significant antinociceptive effects of DORA-12 in the formalin model were also observed in orexin 1 receptor (OX1R) knockout mice, but not orexin 2 receptor (OX2R) or OX1R/OX2R double knockout mice. Mechanical hypersensitivity was significantly reduced with a series of structurally distinct, potent and highly selective ORAs (DORA-2, DORA-12 and DORA-22) in the rat spinal nerve ligation (SNL) injury model of neuropathic pain. Selective pharmacological targeting of OX2R with 2-SORA-7 also reduced pain responses in acute inflammatory (complete Freund's adjuvant) and neuropathic (SNL) rat pain models. Performance on the rotarod test of psychomotor performance and baseline thermal sensitivity were not affected in OX1R/OX2R knockout mice or ORA-treated mice, indicating that the observed pain-reducing effects were not due to sedation or motor deficits. These findings indicate that ORAs have pain-reducing effects across a number of acute and chronic neuropathic preclinical mouse and rat pain models. Further studies on the potential pain-relieving effects of orexin receptor antagonism are warranted. PMID- 27276196 TI - Feature Extraction and Machine Learning for the Classification of Brazilian Savannah Pollen Grains. AB - The classification of pollen species and types is an important task in many areas like forensic palynology, archaeological palynology and melissopalynology. This paper presents the first annotated image dataset for the Brazilian Savannah pollen types that can be used to train and test computer vision based automatic pollen classifiers. A first baseline human and computer performance for this dataset has been established using 805 pollen images of 23 pollen types. In order to access the computer performance, a combination of three feature extractors and four machine learning techniques has been implemented, fine tuned and tested. The results of these tests are also presented in this paper. PMID- 27276195 TI - Deficits in social behavioral tests in a mouse model of alternating hemiplegia of childhood. AB - Social behavioral deficits have been observed in patients diagnosed with alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism and CAPOS syndrome, in which specific missense mutations in ATP1A3, encoding the Na(+), K(+)-ATPase alpha3 subunit, have been identified. To test the hypothesis that social behavioral deficits represent part of the phenotype of Na(+), K(+) ATPase alpha3 mutations, we assessed the social behavior of the Myshkin mouse model of AHC, which has an I810N mutation identical to that found in an AHC patient with co-morbid autism. Myshkin mice displayed deficits in three tests of social behavior: nest building, pup retrieval and the three-chamber social approach test. Chronic treatment with the mood stabilizer lithium enhanced nest building in wild-type but not Myshkin mice. In light of previous studies revealing a broad profile of neurobehavioral deficits in the Myshkin model - consistent with the complex clinical profile of AHC - our results suggest that Na(+), K(+)-ATPase alpha3 dysfunction has a deleterious, but nonspecific, effect on social behavior. By better defining the behavioral profile of Myshkin mice, we identify additional ATP1A3-related symptoms for which the Myshkin model could be used as a tool to advance understanding of the underlying neural mechanisms and develop novel therapeutic strategies. PMID- 27276197 TI - Salidroside Promotes Random Skin Flap Survival in Rats by Enhancing Angiogenesis and Inhibiting Apoptosis. AB - Background Flap necrosis is frequently observed in flap transfer operations. Salidroside has been reported to reduce cell apoptosis by alleviating inflammation and oxidative stress. We investigated the effects of salidroside on the survival of random skin flaps. Materials and Methods The McFarlane flap model was established in 80 rats that were divided into two groups and administered salidroside or saline solution intraperitoneally over 7 days. The area of necrosis and the extent of tissue edema were measured. Angiogenesis was assessed via lead oxide-gelatin angiography, immunohistochemistry for CD34, and VEGF expression. Cell apoptosis was evaluated by expression of cleaved caspase 3, caspase 3, Bax, and Bcl-2. The inflammatory response was evaluated using an ELISA kit for TNF-alpha and IL-6 in serum. Oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA). Results Compared with controls, salidroside-treated flaps featured a greater area of surviving tissue and less edema. It also promoted the expression of VEGF and increased skin flap angiogenesis. Cell apoptosis, inflammation reaction, and oxidative stress were significantly attenuated in the salidroside group. Conclusion Salidroside has a positive effect on improving random skin flap survival. PMID- 27276198 TI - Facial-Hypoglossal End-To-Side Neurorrhaphy: Exploration of the Source of Axonal Sprouting. AB - Background The clinical application of end-to-side (ETS) neurorrhaphy is under debate partly due to a lack of consensus on the source of axonal sprouting. Methods In this study, 24 rats were divided into three groups: sham operation, facial-hypoglossal ETS neurorrhaphy, and end-to-end (ETE) neurorrhaphy. Electrophysiological tests were employed to detect the evoked compound muscle action potentials (CMAPs) in different situations, and the latencies and maximal amplitudes of the CMAPs recorded were compared. Fluorescence retrograde tracing studies, hematoxylin and eosin (HE) staining, and immunohistochemical staining of growth-associated protein 43 (GAP-43) were performed. The number and the diameter of myelinated axons proximal and distal to the coaptation sites were measured. Results Twelve weeks after the surgeries, reinnervation of whisker pad muscles by hypoglossal nerves in both the ETS and ETE groups were confirmed via electrophysiological study. The maximal amplitudes of the CMAPs recorded in different situations and the quantification of myelinated axons supported the coexistence spontaneous collateral sprouting and regenerative sprouting of axons. Double-labeled neurons were found within the hypoglossal nuclear areas in the ETS neurorrhaphy group and HE staining illustrated the axons crossed the coaptation site into the facial acceptor nerve. Although immunohistochemical staining of GAP 43 revealed different timeframes between ETS and ETE neurorrhaphy groups, no significant difference on latency or diameters of the myelinated axons distal to the coaptation sites was noted between ETE and ETS groups. Conclusion Both spontaneous collateral sprouting and regenerative sprouting of axons coexisted following ETS neurorrhaphy, which represents an alternative approach to peripheral nerve reconstruction. PMID- 27276199 TI - Anatomical Origins of Radial Artery Perforators Evaluated Using Color Doppler Ultrasonography. AB - Background The radial artery perforator (RAP) flap has been widely used for covering hand and forearm defects, and real-time accurate perforator mapping is important in planning and elevating the perforator flap. The origins of perforators, especially the superficial and ulnar perforators, arising from the radial artery are very important in the elevation of the RAP flap. Recently, color Doppler ultrasonography (US) using a higher frequency transducer has been developed for high-quality detection of lower flow in smaller vessels. This study aimed to identify the anatomical locations and origins of perforators arising from the radial artery using color Doppler US in healthy volunteers. Methods Twenty forearms of 10 volunteers were examined. Results In total, 120 perforators arising from the radial artery were identified 15 cm proximal to the distal wrist crease, with an average of six perforators per forearm. More than half the perforators (n = 72, 60%) were located within 50 mm proximal to the distal wrist crease. Regarding the perforator origins in the axial view, 40 perforators (33%) were located in the radial aspect of the radial artery, 47 (39%) in the ulnar aspect, 15 (13%) in the superficial aspect, and 18 (15%) in the deep aspect. In total, 62 (52%) perforators were located in the superficial and ulnar areas, which are important in nourishing and elevating the RAP flap. Conclusion We are the first to evaluate RAP using color Doppler US. This noninvasive, convenient, and real-time technique could be useful for preoperative planning and reliably elevating the RAP flaps. PMID- 27276200 TI - Value and Efficacy of Sentinel Lymph Node Diagnostics in Patients With Penile Carcinoma With Nonpalpable Inguinal Lymph Nodes: Five-Year Follow-up. AB - PURPOSE: Sentinel lymph node biopsy (SLNB) has been described as a minimally invasive method for lymph node staging in patients with a penile carcinoma and nonpalpable inguinal nodes in national and international guidelines of involved professional societies. However, this method is rarely used. The aim of this study was to validate reliability and morbidity of this method and to discuss radiation exposure of persons involved. METHODS: Twenty-eight patients with histologically negative sentinel lymph nodes in 47 groins with nonpalpable inguinal lymph nodes were included in this study (17 T1(a/b)-, 8 T2- and 3 T3 stages). We recorded prospectively all cases of lymph node recurrence and complications in patients with initially nonpalpable inguinal lymph nodes and histologically negative sentinel lymph nodes. False-negative findings and morbidity were calculated as qualitative criteria. Inguinal regions with palpable lymph nodes and/or evidence of metastases were not considered in accordance with the guidelines. RESULTS: During a median follow-up of 68 (4-131) months, we observed one case of bilateral lymph node recurrence and one case of prolonged inguinal lymphorrhea, which could be managed conservatively. Per inguinal region, false-negative rate was 4.25%, and morbidity rate was 2.12%; seen per patient, the rates were both 3.57%. CONCLUSIONS: Sentinel lymph node biopsy under use of radioactive tracers is a reliable method of lymph node staging in patients with penile carcinoma and nonpalpable inguinal lymph nodes. The methodical complexity is justified by high reliability and low radiation exposure for both patient and medical staff and low morbidity rates. PMID- 27276201 TI - Uremic Leontiasis Ossea in a Patient With Chronic Renal Insufficiency Demonstrated on Bone Scintigraphy. AB - A 37-year-old woman with chronic renal insufficiency underwent bone scintigraphy to evaluate renal osteodystrophy (ROD). Markedly increased uptakes were shown in the maxilla and the mandible, which suggested extensive maxillary and mandibular hypertrophy. CT image revealed that diffuse bony thickening and ground-glass appearance in the skull, maxilla, and mandible with poor distinction of the corticomedullary junction. Whole-body bone scintigraphy images also demonstrated various skeletal characteristics of ROD. This case emphasizes the utility of bone scintigraphy for the surveillance of the whole body in ROD. PMID- 27276202 TI - Clinical Impact of 68Ga-PSMA PET/CT in a Patient With Biochemical Recurrence of Prostate Cancer. AB - A 64-year-old man with history of prostate adenocarcinoma underwent radical prostatectomy in 2003. He remained with undetectable prostate-specific antigen (PSA) levels until 2014, when he then presented rising serum PSA levels and performed a Tc-MDP bone scan that was negative for metastases. In August 2015, his PSA was 4.89 ng/dL, and restaging images with pelvic MR and F-FDG PET/CT were both negative. Therefore, the patient underwent a Ga-PSMA PET/CT that showed marked tracer uptake in a single mediastinal lymph node. Histopathology demonstrated metastatic adenocarcinoma secondary to prostate cancer, altering patient management to hormone therapy instead of pelvic radiotherapy. PMID- 27276203 TI - 68Ga-DOTATATE Breast Uptake and Expression in Breast Milk. AB - The excretion of Ga-DOTA-Octreotate (DOTATATE) and related somatostatin analogues in breast milk has not been demonstrated. We report a case of a 34-year-old woman, 7 months postpartum and breastfeeding, who was referred for DOTATATE imaging after the diagnosis of appendiceal carcinoid and subsequent appendectomy. Prominent breast uptake was noted. A breast milk sample from the patient at 90 minutes postinjection was assayed in a gamma counter and shown to have a concentration of 5.6 Bq/g per MBq administered. The excretion of DOTATATE in breast milk is important to consider when providing radiation safety advice to breastfeeding patients. PMID- 27276205 TI - Left Main Coronary Artery Atresia in Young Man Examined With 99mTc-Tetrofosmin SPECT: A Rare and Challenging Anomaly. AB - A young man underwent Tc-tetrofosmin cardiac SPECT/CT for the evaluation of the 8 month history of exertional dyspnea without chest pain. Tc-tetrofosmin SPECT demonstrated absence of perfusion defects and a mildly decreased uptake in post stress images, consistent with artifact, in the inferior myocardium. Cardiac catheterization showed a large right and a small left coronary artery opacified retrogradely by right collateral vessels without connections between the left main and the left coronary artery. In patients with anomalous coronary arteries, Tc SPECT can shows absence of perfusion defects, in the presence of a collateral circulation. PMID- 27276204 TI - PET/CT Response Criteria (European Organization for Research and Treatment of Cancer) Predict Survival Better Than Response Evaluation Criteria in Solid Tumors in Locally Advanced Cervical Cancer Treated With Chemoradiation. AB - PURPOSE: To investigate whether the ratio of SUVs measured with F-FDG PET/CT between pretreatment and posttreatment has prognostic value in patients with locally advanced cervical cancer treated with primary chemoradiation therapy. METHODS: Cases of locally advanced cervical cancer (International Federation of Gynecology and Obstetrics stages IB1 to IVA) treated with a nonsurgical curative modality (172 cases including chemoradiation or radiation therapy) were reviewed. F-FDG PET/CT parameters, including SUVmax and SUVmean, were evaluated by F-FDG PET/CT performed prior to treatment and 6 weeks after the end of treatment. Metabolic response was evaluated according to the European Organization for Research and Treatment of Cancer guidelines and was compared with radiologic response measured according to the Response Evaluation Criteria In Solid Tumours (RECIST). RESULTS: In total, 142 patients receiving chemoradiation showed radiologic responses (median 56% decrease in maximal diameter), whereas 160 and 146 patients showed metabolic responses measured with SUVmax and SUVmean, respectively (73% decrease in SUVmax; 48% decrease in SUVmean). Radiologic response and metabolic response were significantly correlated for SUVmax and SUVmean (P = 0.0009; P = 0.0457, respectively). Kaplan-Meier analysis revealed significant differences in overall survival and progression-free survival between the responder and nonresponder groups, based on the European Organization for Research and Treatment of Cancer criteria (both P < 0.001), whereas no significant difference was found when using RECIST criteria (P = 0.058, P = 0.088, respectively). CONCLUSIONS: F-FDG PET/CT parameters are good prognostic markers for the response of cervical cancer patients to concurrent chemoradiation therapy, as compared with the RECIST criteria. PMID- 27276206 TI - Intrapatient Comparison of 111In-PSMA I&T SPECT/CT and Hybrid 68Ga-HBED-CC PSMA PET in Patients With Early Recurrent Prostate Cancer. AB - PURPOSE: The aim of this study was to evaluate the detection efficiency of In PSMA-I&T SPECT/CT in comparison to hybrid Ga-PSMA HBED-CC PET in patients with early recurrent prostate cancer. METHODS: Twenty-two patients (mean age, 68.2 +/- 6.8 years; range, 52-76 years) with rising prostate-specific antigen (PSA; median, 1.03 ng/mL; range, 0.2-7.2ng/mL) and known positive lesions in hybrid Ga PSMA HBED-CC PET scheduled for salvage surgery were included. Whole-body scintigraphy and SPECT/CT were performed 4 hours after application of 147.0 +/- 24.8 MBq (range, 90-183 MBq) In-PSMA I&T. Images were evaluated for suspected lesions, and conspicuity of all lesions was rated using a 4-point-scale (0 = not seen, 1 = retrospectively seen in knowledge of Ga-PSMA HBED-CC PET, 2 = low signal, 3 = high signal). Tumor-to-background ratios were determined for SPECT and PET and compared. Tumor-to-background ratio of SPECT was correlated with lesion size as well as patients' Gleason score and PSA level. RESULTS: In-PSMA I&T SPECT/CT detected 14 of 29 PET-positive lesions (48.3%) with no additional lesions identified with In-PSMA I&T SPECT/CT. There was a significant weak to moderate correlation of PSA level with tumor-to-background ratio of In-PSMA I&T SPECT/CT (correlation coefficient r = 0.6406; 95% confidence interval, 0.1667 0.8741; P = 0.0136). There was no significant difference (P > 0.05), but a weak trend toward a higher detectability in In-PSMA I&T SPECT/CT regarding lesion size and initial PSA level. CONCLUSIONS: In a preselected collective of recurrent prostate cancer patients with low PSA values, In-PSMA I&T SPECT/CT showed lower detection rates than hybrid Ga-HBED-CC PSMA PET. However, In-PSMA I&T SPECT/CT showed a patient based detection rate of 59%, making it a potentially valuable imaging tool where PET is not available apart from its proven value as a PSMA targeted probe for radioguided surgery. PMID- 27276207 TI - Prognostic Value of 68Ga-NOTA-RGD PET/CT for Predicting Disease-Free Survival for Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy and Surgery: A Comparison Study With Dynamic Contrast Enhanced MRI. AB - PURPOSE: We performed pretreatment angiogenesis imaging (Ga-NOTA-arginyl-glycyl aspartic acid [RGD] PET/CT) to compare its prognostic value to dynamic contrast enhanced (DCE) MRI in breast cancer patients. METHODS: Forty-four female patients with stage II or III breast cancer (aged 47.3 +/- 8.1 years) were prospectively enrolled and underwent Ga-NOTA-RGD PET/CT and DCE-MRI imaging. All patients received neoadjuvant chemotherapy and underwent surgery. With pretreatment Ga NOTA-RGD PET/CT, SUVmax of the tumor in the torso (-T) and regional (-R) images were measured. With pretreatment DCE-MRI, the largest diameter of the tumor and maximum enhancement index (EImax; EImax = [highest signal / baseline signal] - 1) of the tumor were assessed. RESULTS: Ten patients (22.7%) were found to have breast cancer recurrence after 17.9 +/- 11.2 months. The SUVmax-R (P = 0.017, cutoff >2.79) of Ga-NOTA-RGD PET/CT, the largest diameter of tumor (P = 0.017, cutoff >6.3 cm), and the EImax (P = 0.008, cutoff >5.38) of DCE-MRI showed significant results by univariate analysis. The 3-year disease-free survival of SUVmax-R was 91.7% versus 59.1% by Kaplan-Meier analysis (hazard ratio, 5.379). Multivariable analysis demonstrated that SUVmax-R with tumor diameter or EImax were the significant parameters. In addition, the combined parameters of SUVmax-R and EImax revealed better predictive value for prediction of breast cancer recurrence (75.0%) than each parameter of SUVmax-R (64.2%) and EImax (68.7%). CONCLUSIONS: Increased angiogenic activity of regional Ga-NOTA-RGD PET/CT (SUVmax R) can be an early prognostic marker for the prediction of breast cancer recurrence. PMID- 27276208 TI - 18F-FDG PET/CT Osteometabolic Activity in Metastatic Parathyroid Carcinoma. AB - Parathyroid cancer is an uncommon type of malignancy, which is frequently associated with poor prognosis. Clinical manifestations are caused by elevated serum calcium and parathyroid hormone (PTH). Diagnostic imaging studies as neck ultrasonography, technetium Tc Tc-sestamibi whole body scintigraphy, CT, and MR are already established tools for this malignancy. Nevertheless, the role of F FDG PET/CT remains unknown in this scenario, with few published studies in literature. Hence, in this article, we aimed to report an illustrative case of increased skeletal FDG uptake associated with high calcium and PTH levels. PMID- 27276209 TI - Uterine Cervical Metastasis From Primary Rectal Adenocarcinoma on PET/CT and MRI. AB - FDG avid uterine cervical masses are most commonly due to primary cervical carcinoma; however, history and differential diagnoses are critical when interpreting FDG PET/CT studies. A 51-year-old woman with newly diagnosed moderately differentiated adenocarcinoma of the rectum underwent FDG PET/CT for staging, which revealed the hypermetabolic primary rectal tumor and nodal metastases. Additionally, FDG avid focus in the anterior cervix without a CT correlate was present. Cervical metastasis was suspected, and further evaluation with MRI and histopathologic correlation was recommended, which confirmed cervical metastasis. This case illustrates an unusual case of FDG-avid cervical metastasis from rectal adenocarcinoma. PMID- 27276210 TI - Allergic Reaction to Ginkgo Nut on FDG PET/CT. AB - We report the case of a 36-year-old woman who previously underwent total thyroidectomy for papillary thyroid carcinoma. F FDG PET/CT images demonstrated multiple lymph nodes with increased FDG uptake in the neck, chest, and abdomen and diffusely increased FDG uptake in the spleen, which were highly suspicious findings for malignant lymphoma. However, subsequent biopsy of axillary lymph node presented reactive hyperplasia. Detailed history revealed that the patient had a history of generalized edema and severe arthralgia after contact with ginkgo nut one week ago. This case highlights allergic reaction mimicking lymphoma on FDG PET/CT. PMID- 27276211 TI - False-Positive Finding on 18F FDG PET/CT: Report of a Rare Case With Xanthogranulomatous Inflammation in the Spinal Epidural Space. AB - Xanthogranulomatous inflammation in the spinal epidural space is extremely rare. We report a case of a 62-year-old man with a xanthogranulomatous inflammation in the spinal epidural space mistaken for lymphoma because of its avid F FDG uptake on PET/CT. This case emphasizes the need for caution when evaluating a spinal epidural mass using F FDG PET/CT as xanthogranulomatous inflammation can induce a false-positive reading on F-FDG PET/CT. PMID- 27276212 TI - CRISPR/Cas9-Based Efficient Genome Editing in Clostridium ljungdahlii, an Autotrophic Gas-Fermenting Bacterium. AB - Acetogenic bacteria have the potential to convert single carbon gases (CO and CO2) into a range of bulk chemicals and fuels. Realization of their full potential is being impeded by the absence of effective genetic tools for high throughput genome modification. Here we report the development of a highly efficient CRISPR/Cas9 system for rapid genome editing of Clostridium ljungdahlii, a paradigm for the commercial production of ethanol from synthesis gas. Following the experimental selection of two promoters (Pthl and ParaE) for expression of cas9 and the requisite single guide RNA (sgRNA), the efficiency of system was tested by making precise deletions of four genes, pta, adhE1, ctf and pyrE. Deletion efficiencies were 100%, >75%, 100% and >50%, respectively. The system overcomes the deficiencies of currently available tools (more rapid, no added antibiotic resistance gene, scarless and minimal polar effects) and will find utility in other acetogens, including the pathogen Clostridium difficile. PMID- 27276214 TI - Nutrition in the cause and prevention of cancer: An update. PMID- 27276213 TI - Functional Characterization of Schizophrenia-Associated Variation in CACNA1C. AB - Calcium channel subunits, including CACNA1C, have been associated with multiple psychiatric disorders. Specifically, genome wide association studies (GWAS) have repeatedly identified the single nucleotide polymorphism (SNP) rs1006737 in intron 3 of CACNA1C to be strongly associated with schizophrenia and bipolar disorder. Here, we show that rs1006737 marks a quantitative trait locus for CACNA1C transcript levels. We test 16 SNPs in high linkage disequilibrium with rs1007637 and find one, rs4765905, consistently showing allele-dependent regulatory function in reporter assays. We find allele-specific protein binding for 13 SNPs including rs4765905. Using protein microarrays, we identify several proteins binding >=3 SNPs, but not control sequences, suggesting possible functional interactions and combinatorial haplotype effects. Finally, using circular chromatin conformation capture, we show interaction of the disease associated region including the 16 SNPs with the CACNA1C promoter and other potential regulatory regions. Our results elucidate the pathogenic relevance of one of the best-supported risk loci for schizophrenia and bipolar disorder. PMID- 27276215 TI - Honokiol targets mitochondria to halt cancer progression and metastasis. AB - Cancer continues to be the leading cause of death worldwide. Plants have a long history of use in the treatment of cancer. Honokiol (HNK) is an important bioactive compound found in the bark of Magnolia tree, and has been shown to inhibit cancer growth and metastasis in many cell types in vitro and in animal models. Resistance to chemotherapy and radiotherapy is the major obstacle for cure of cancer. Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death, suggesting that HNK not only directly inhibits primary cancers and metastasis, but also has potential to overcome drug resistance. Ultimately, this may mean that HNK could be combined with traditional chemotherapies administered at lower doses to significantly reduce toxicity, meanwhile enhance efficacy. As a natural compound, HNK is composed of polyphenols and has been described in many studies targeting multiple key cell signaling molecules. Mitochondria are the main hub for cellular energy production and play an important role in cell survival, and are the key target identified for HNK to mediate cancer cell death, survival, and metastasis. In this review, we have summarized different aspects of HNK's anti-cancer effects from recent accumulated literature, as well as the underlying molecular mechanisms. This review is primarily focused on the effects of HNK on epidermal growth factor receptor (EGFR) and signal transduction and activator of transcription 3 (STAT3) signaling, as well as the broader regulation of mitochondrial function and cancer cell metabolism. PMID- 27276216 TI - Small Molecule Recognition and Tools to Study Modulation of r(CGG)(exp) in Fragile X-Associated Tremor Ataxia Syndrome. AB - RNA transcripts containing expanded nucleotide repeats cause many incurable diseases via various mechanisms. One such disorder, fragile X-associated tremor ataxia syndrome (FXTAS), is caused by a noncoding r(CGG) repeat expansion (r(CGG)(exp)) that (i) sequesters proteins involved in RNA metabolism in nuclear foci, causing dysregulation of alternative pre-mRNA splicing, and (ii) undergoes repeat associated non-ATG translation (RANT), which produces toxic homopolymeric proteins without using a start codon. Here, we describe the design of two small molecules that inhibit both modes of toxicity and the implementation of various tools to study perturbation of these cellular events. Competitive Chemical Cross Linking and Isolation by Pull Down (C-Chem-CLIP) established that compounds bind r(CGG)(exp) and defined small molecule occupancy of r(CGG)(exp) in cells, the first approach to do so. Using an RNA GFP mimic, r(CGG)(exp)-Spinach2, we observe that our optimal designed compound binds r(CGG)(exp) and affects RNA localization by disrupting preformed RNA foci. These events correlate with an improvement of pre-mRNA splicing defects caused by RNA gain of function. In addition, the compounds reduced levels of toxic homopolymeric proteins formed via RANT. Polysome profiling studies showed that small molecules decreased loading of polysomes onto r(CGG)(exp), explaining decreased translation. PMID- 27276217 TI - Structure of a Berberine Bridge Enzyme-Like Enzyme with an Active Site Specific to the Plant Family Brassicaceae. AB - Berberine bridge enzyme-like (BBE-like) proteins form a multigene family (pfam 08031), which is present in plants, fungi and bacteria. They adopt the vanillyl alcohol-oxidase fold and predominantly show bi-covalent tethering of the FAD cofactor to a cysteine and histidine residue, respectively. The Arabidopsis thaliana genome was recently shown to contain genes coding for 28 BBE-like proteins, while featuring four distinct active site compositions. We determined the structure of a member of the AtBBE-like protein family (termed AtBBE-like 28), which has an active site composition that has not been structurally and biochemically characterized thus far. The most salient and distinguishing features of the active site found in AtBBE-like 28 are a mono-covalent linkage of a histidine to the 8alpha-position of the flavin-isoalloxazine ring and the lack of a second covalent linkage to the 6-position, owing to the replacement of a cysteine with a histidine. In addition, the structure reveals the interaction of a glutamic acid (Glu426) with an aspartic acid (Asp369) at the active site, which appear to share a proton. This arrangement leads to the delocalization of a negative charge at the active site that may be exploited for catalysis. The structure also indicates a shift of the position of the isoalloxazine ring in comparison to other members of the BBE-like family. The dioxygen surrogate chloride was found near the C(4a) position of the isoalloxazine ring in the oxygen pocket, pointing to a rapid reoxidation of reduced enzyme by dioxygen. A T DNA insertional mutant line for AtBBE-like 28 results in a phenotype, that is characterized by reduced biomass and lower salt stress tolerance. Multiple sequence analysis showed that the active site composition found in AtBBE-like 28 is only present in the Brassicaceae, suggesting that it plays a specific role in the metabolism of this plant family. PMID- 27276218 TI - Identifying Where REDD+ Financially Out-Competes Oil Palm in Floodplain Landscapes Using a Fine-Scale Approach. AB - Reducing Emissions from Deforestation and forest Degradation (REDD+) aims to avoid forest conversion to alternative land-uses through financial incentives. Oil-palm has high opportunity costs, which according to current literature questions the financial competitiveness of REDD+ in tropical lowlands. To understand this more, we undertook regional fine-scale and coarse-scale analyses (through carbon mapping and economic modelling) to assess the financial viability of REDD+ in safeguarding unprotected forest (30,173 ha) in the Lower Kinabatangan floodplain in Malaysian Borneo. Results estimate 4.7 million metric tons of carbon (MgC) in unprotected forest, with 64% allocated for oil-palm cultivations. Through fine-scale mapping and carbon accounting, we demonstrated that REDD+ can outcompete oil-palm in regions with low suitability, with low carbon prices and low carbon stock. In areas with medium oil-palm suitability, REDD+ could outcompete oil palm in areas with: very high carbon and lower carbon price; medium carbon price and average carbon stock; or, low carbon stock and high carbon price. Areas with high oil palm suitability, REDD+ could only outcompete with higher carbon price and higher carbon stock. In the coarse-scale model, oil palm outcompeted REDD+ in all cases. For the fine-scale models at the landscape level, low carbon offset prices (US $3 MgCO2e) would enable REDD+ to outcompete oil-palm in 55% of the unprotected forests requiring US $27 million to secure these areas for 25 years. Higher carbon offset price (US $30 MgCO2e) would increase the competitiveness of REDD+ within the landscape but would still only capture between 69%-74% of the unprotected forest, requiring US $380-416 million in carbon financing. REDD+ has been identified as a strategy to mitigate climate change by many countries (including Malaysia). Although REDD+ in certain scenarios cannot outcompete oil palm, this research contributes to the global REDD+ debate by: highlighting REDD+ competitiveness in tropical floodplain landscapes; and, providing a robust approach for identifying and targeting limited REDD+ funds. PMID- 27276219 TI - Measuring the Impact of Research: Lessons from the UK's Research Excellence Framework 2014. AB - Impactful academic research plays a stellar role in society, pressing to ask the question of how one measures the impact created by different areas of academic research. Measuring the societal, cultural, economic and scientific impact of research is currently the priority of the National Science Foundation, European Commission and several research funding agencies. The recently concluded United Kingdom's national research quality exercise, the Research Excellence Framework (REF) 2014, which piloted impact assessment as part of the overall evaluation offers a lens to view how impact of research in different disciplines can be measured. Overall research quality was assessed through quality of outputs, 'impact' and research environment. We performed two studies using the REF 2014 as a case study. The first study on 363 Impact Case Studies (ICSs) submitted in 5 research areas (UoAs) reveals that, in general, the impact scores were constructed upon a combination of factors i.e. quantity of quartile-one (Q1) publications, quantity and value of grants/income, number of researchers stated in the ICSs, spin-offs created, discoveries/patents and presentation of esteem data, informing researchers/ academics of the factors to consider in order to achieve a better impact score in research impact assessments. However, there were differences among disciplines in terms of the role played by the factors in achieving their overall scores for the ICSs. The outcome of this study is thus a set of impact indicators, and their relationship with the overall score of impact of research in different disciplines as determined in REF2014, which would in the first instance provide some answers to impact measures that would be useful for researchers in different disciplines. The second study extracts the general themes of impact reported by universities by performing a word frequency analysis in all the ICSs submitted in the five chosen research areas, which were substantially varied owing to their fields. PMID- 27276220 TI - Structural and Functional Brain Abnormalities in Attention-Deficit/Hyperactivity Disorder and Obsessive-Compulsive Disorder: A Comparative Meta-analysis. AB - IMPORTANCE: Patients with attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) share impaired inhibitory control. However, it is unknown whether impairments are mediated by shared or disorder-specific neurostructural and neurofunctional abnormalities. OBJECTIVE: To establish shared and disorder-specific structural, functional, and overlapping multimodal abnormalities in these 2 disorders through a voxel-based meta-analytic comparison of whole-brain gray matter volume (GMV) and functional magnetic resonance imaging (fMRI) studies of inhibition in patients with ADHD and OCD. DATA SOURCES: Literature search using PubMed, ScienceDirect, Web of Knowledge, and Scopus up to September 30, 2015. STUDY SELECTION: Whole-brain voxel-based morphometry (VBM) or fMRI studies during inhibitory control comparing children and adults with ADHD or OCD with controls. DATA EXTRACTION AND SYNTHESIS: Voxel-wise meta-analyses of GMV or fMRI differences were performed using Seed-based d-Mapping. Regional structure and function abnormalities were assessed within each patient group and then a quantitative comparison was performed of abnormalities (relative to controls) between ADHD and OCD. MAIN OUTCOMES AND MEASURES: Meta-analytic disorder-specific and shared abnormalities in GMV, in inhibitory fMRI, and in multimodal functional and structural measures. RESULTS: The search revealed 27 ADHD VBM data sets (including 931 patients with ADHD and 822 controls), 30 OCD VBM data sets (928 patients with OCD and 942 controls), 33 ADHD fMRI data sets (489 patients with ADHD and 591 controls), and 18 OCD fMRI data sets (287 patients with OCD and 284 controls). Patients with ADHD showed disorder-contrasting multimodal structural (left z = 1.904, P < .001; right z = 1.738, P < .001) and functional (left z = 1.447, P < .001; right z = 1.229, P < .001) abnormalities in bilateral basal ganglia/insula, which were decreased in GMV and function in patients with ADHD relative to those with OCD (and controls). In OCD patients, they were enhanced relative to controls. Patients with OCD showed disorder-specific reduced function and structure in rostral and dorsal anterior cingulate/medial prefrontal cortex (fMRI z = 2.113, P < .001; VBM z = 1.622, P < .001), whereas patients with ADHD showed disorder-specific underactivation predominantly in the right ventrolateral prefrontal cortex (z = 1.229, P < .001). Ventromedial prefrontal GMV reduction was shared in both disorders relative to controls. CONCLUSIONS AND RELEVANCE: Shared impairments in inhibitory control, rather than representing a transdiagnostic endophenotype in ADHD and OCD, were associated with disorder differential functional and structural abnormalities. Patients with ADHD showed smaller and underfunctioning ventrolateral prefrontal/insular-striatal regions whereas patients with OCD showed larger and hyperfunctioning insular-striatal regions that may be poorly controlled by smaller and underfunctioning rostro/dorsal medial prefrontal regions. PMID- 27276221 TI - Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival. AB - Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience. PMID- 27276222 TI - Public Acceptability in the UK and USA of Nudging to Reduce Obesity: The Example of Reducing Sugar-Sweetened Beverages Consumption. AB - BACKGROUND: "Nudging"-modifying environments to change people's behavior, often without their conscious awareness-can improve health, but public acceptability of nudging is largely unknown. METHODS: We compared acceptability, in the United Kingdom (UK) and the United States of America (USA), of government interventions to reduce consumption of sugar-sweetened beverages. Three nudge interventions were assessed: i. reducing portion Size, ii. changing the Shape of the drink containers, iii. changing their shelf Location; alongside two traditional interventions: iv. Taxation and v. Education. We also tested the hypothesis that describing interventions as working through non-conscious processes decreases their acceptability. Predictors of acceptability, including perceived intervention effectiveness, were also assessed. Participants (n = 1093 UK and n = 1082 USA) received a description of each of the five interventions which varied, by randomisation, in how the interventions were said to affect behaviour: (a) via conscious processes; (b) via non-conscious processes; or (c) no process stated. Acceptability was derived from responses to three items. RESULTS: Levels of acceptability for four of the five interventions did not differ significantly between the UK and US samples; reducing portion size was less accepted by the US sample. Within each country, Education was rated as most acceptable and Taxation the least, with the three nudge-type interventions rated between these. There was no evidence to support the study hypothesis: i.e. stating that interventions worked via non-conscious processes did not decrease their acceptability in either the UK or US samples. Perceived effectiveness was the strongest predictor of acceptability for all interventions across the two samples. CONCLUSION: In conclusion, nudge interventions to reduce consumption of sugar-sweetened beverages seem similarly acceptable in the UK and USA, being more acceptable than taxation, but less acceptable than education. Contrary to prediction, we found no evidence that highlighting the non-conscious processes by which nudge interventions may work decreases their acceptability. However, highlighting the effectiveness of all interventions has the potential to increase their acceptability. PMID- 27276223 TI - Clinical Staging and Prognostic Factors in Folliculotropic Mycosis Fungoides. AB - IMPORTANCE: Large case series suggest that patients with folliculotropic mycosis fungoides (FMF) have a worse prognosis than patients with classic mycosis fungoides (MF). However, recent studies described a subgroup of patients with FMF with a more favorable prognosis. Distinction between indolent and aggressive FMF may have important therapeutic consequences but is hampered by the inability of the current tumor-node-metastasis-blood (TNMB) staging system to classify patients with FMF in a clinically meaningful way. OBJECTIVE: To differentiate between indolent and aggressive FMF using clinicopathological criteria and to define prognostic factors in patients with FMF. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, we followed 203 patients with FMF, included in the Dutch Cutaneous Lymphoma Registry between October 1985 and May 2014 at a tertiary referral center hosting the Dutch Cutaneous Lymphoma Registry. Overall, 220 patients with FMF had been registered, but 17 patients with incomplete follow-up data or a history of classic MF were excluded. MAIN OUTCOMES AND MEASURES: Main outcomes included clinical and histological characteristics, disease progression, and survival. Prognostic factors were investigated using Cox proportional hazard regression analysis. Distinction between early plaque-stage FMF and advanced plaque-stage FMF was made by a blinded review of skin biopsy specimens from patients presenting with plaques. RESULTS: In a cohort of 147 men and 56 women (median [range] age, 59 [15-93] years), patients with histologically early plaque-stage FMF had a very similar overall survival (OS) rate to patients with only patches and/or follicular papules (10-year OS, 71% vs 80%), while the survival rate of patients with histologically advanced plaque-stage FMF was almost identical to that of patients presenting with tumors (10-year OS, 25% vs 27%). Subsequently, 3 clinical subgroups with significantly different survival data were distinguished: early skin-limited FMF (group A; n = 84; 5-year and 10-year OS, 92% and 72%); advanced skin-limited FMF (group B; n = 102; 5-year and 10-year OS, 55% and 28%); and FMF presenting with extracutaneous disease (group C; n = 17; 5-year and 10-year OS, 23% and 2%). Age at diagnosis, large cell transformation and secondary bacterial infection were independent risk factors for disease progression and/or poor survival. CONCLUSIONS AND RELEVANCE: The results of this study provide useful criteria to differentiate between indolent and aggressive FMF and confirm the existence of a subgroup of FMF with a favorable prognosis. PMID- 27276224 TI - Chicken or the egg: ST elevation in lead aVR or SYNTAX score. AB - BACKGROUND: ST-segment elevation in lead aVR (STEaVR) anticipates left main and/or three-vessel disease (LM/3VD) in patients with acute coronary syndromes. STEaVR is generally reciprocal to and accompanied by ST-segment depression (STD) in the precordial leads. SYNTAX score (SS) is an angiographic scoring system and is widely used to evaluate the severity and complexity of coronary artery disease. The purpose of our study was to assess the relationship between STEaVR and SS. METHODS: We performed a retrospective analysis of 117 patients with non ST-segment elevation acute coronary syndrome (NSTEACS). Electrocardiograms at presentation were reviewed, especially for ST-segment elevation of >= 0.05 mV in lead aVR and STD of >= 0.05 mV in more than two contiguous leads. All lesions causing >= 50% stenosis in a coronary artery with a diameter of >= 1.5 mm were included in the SS calculation. SS was divided into two groups: >= 23: high, < 23: low. RESULTS: Among the 117 patients, 80 (68.4%) had STEaVR and 37 (31.6%) did not. Patients with STEaVR had a higher SS and higher rate of LM/3VD (85 vs 67.6%, p < 0.001; 86.2 vs 72.9%, p = 0.03, respectively) than those without STEaVR. On multivariate analysis, STEaVR [odds ratio (OR) 1.85; 95% confidence interval (CI): 1.20-3.97, p = 0.03] and STD in leads V1-V4 (OR 2.14; 95% CI: 1.46 4.23, p = 0.002) were independent predictors of a high SS. CONCLUSION: This study demonstrated that STEaVR was an independent predictor of a high SS. PMID- 27276225 TI - Ultrasound Tutorials in Under 10 Minutes: Experience and Results. AB - OBJECTIVE: The objective of the present study was to validate the use of web based tutorials to teach technical skills in pediatric ultrasound. MATERIALS AND METHODS: A series of 10 video tutorials, each of which was less than 10 minutes long, was created to improve the education of radiology trainees in terms of their ultrasound technique. Pediatric radiology fellow trainees from our institution in the United States and radiology resident trainees from our partner institution in Ethiopia were invited to participate in the study. Validation of the video tutorials was performed using two learning modules that focused on the renal bladder and the right upper quadrant (RUQ). Pretest and posttest skill and confidence assessments were also conducted. After watching the tutorials, the trainees completed questionnaires that assessed the reach, appeal, and learning effectiveness of the modules. RESULTS: Ten fellow trainees and eight resident trainees participated in the study. The fellows were invited to evaluate both the RUQ and the renal bladder learning modules, whereas the residents evaluated the RUQ module only. Before reviewing the RUQ module, the fellows had performed a median of four RUQ ultrasound examinations, whereas the residents had performed a median of 400 RUQ ultrasound examinations. After the trainees viewed the learning module, the median skills test scores of the fellows increased from 20 to 37.5 (highest possible score, 45) (p < 0.01), and those of the residents increased from 38 to 40 (highest possible score, 40) (p = 0.04). With a total possible score of 15, the median confidence score improved from 8 to 11 for fellows (p < 0.01) and from 13.5 to 14.5 for residents (p = 0.04). After the fellows viewed the renal bladder learning module, their median skills test scores increased from 20 to 37.5 (highest possible score, 40) (p < 0.01), and their median confidence score increased from 8.5 to 11 (highest possible score, 15) (p = 0.01). Trainees gave the tutorials positive ratings overall. CONCLUSION: Radiology fellow trainees and resident trainees with disparate backgrounds in ultrasound showed significant improvement in their technical skills in pediatric ultrasound and confidence after viewing the tutorials. The web-based design of the tutorials allows integration of international pediatric radiology training communities. PMID- 27276227 TI - Total Synthesis of (+)-Conolidine by the Gold(I)-Catalyzed Cascade Cyclization of a Conjugated Enyne. AB - A total synthesis of (+)-conolidine has been achieved via the gold(I)-catalyzed cascade cyclization of a conjugated enyne. Remarkably, this strategy allowed for the simultaneous formation of the indole ring and the ethylidene-substituted piperidine moiety of (+)-conolidine under homogeneous gold catalysis in an enantioselective manner (88-91% ee). PMID- 27276226 TI - Study of LAT1 Expression in Brain Metastases: Towards a Better Understanding of the Results of Positron Emission Tomography Using Amino Acid Tracers. AB - Positron emission tomography using radiolabeled amino acid (PET-AA) appears to be promising in distinguishing between recurrent tumour and radionecrosis in the follow-up of brain metastasis (BM). The amino acid transporter LAT1 and its cofactor CD98, which are involved in AA uptake, have never been investigated in BM. The aim of our study was to determine and compare the expression of LAT1 and CD98 in BM and in non-tumoral brain tissue (NT). The expression of LAT1 and CD98 were studied by immunohistochemistry in 67 BM, including 18 BM recurrences after radiotherapy, in 53 NT, and in 13 cases of patients with previously irradiated brain tumor and investigated by [18F] FDOPA-PET. LAT1 and CD98 expression were detected in 98.5% and 59.7% of BM respectively and were significantly associated with BM tissue as compared to NT (p<0.001). LAT1 expression in recurrent BM was significantly increased as compared to newly occurring BM. Ten cases investigated by [18F] FDOPA-PET corresponding to recurrent BM displayed significant [18F] FDOPA uptake and LAT1 overexpression whereas three cases corresponding to radionecrosis showed no or low uptake and LAT1 expression. LAT1 expression level and [18F] FDOPA uptake were significantly correlated. In conclusion, we hypothesized that BM may overexpress the AA transporter LAT1. We have shown that LAT1 overexpression was common in BM and was specific for BM as compared to healthy brain. These results could explain the specific BM uptake on PET-AA. PMID- 27276228 TI - Subtle Ecological Gradient in the Tropics Triggers High Species-Turnover in a Local Geographical Scale. AB - Our perception of diversity, including both alpha- and beta-diversity components, depends on spatial scale. Studies of spatial variation of the latter are just starting, with a paucity of research on beta-diversity patterns at smaller scales. Understanding these patterns and the processes shaping the distribution of diversity is critical to describe this diversity, but it is paramount in conservation too. Here, we investigate the diversity and structure of a tropical community of herbivorous beetles at a reduced local scale of some 10 km2, evaluating the effect of a small, gradual ecological change on this structure. We sampled leaf beetles in the Nui Chua National Park (S Vietnam), studying changes in alpha- and beta-diversity across an elevation gradient up to 500 m, encompassing the ecotone between critically endangered lowland dry deciduous forest and mixed evergreen forest at higher elevations. Leaf beetle diversity was assessed using several molecular tree-based species delimitation approaches (with mtDNA cox1 data), species richness using rarefaction and incidence-based diversity indexes, and beta-diversity was investigated decomposing the contribution of species turnover and nestedness. We documented 155 species in the area explored and species-richness estimates 1.5-2.0x higher. Species diversity was similar in both forest types and changes in alpha-diversity along the elevation gradient showed an expected local increase of diversity in the ecotone. Beta-diversity was high among forest paths (average Sorensen's dissimilarity = 0.694) and, tentatively fixing at 300 m the boundary between otherwise continuous biomes, demonstrated similarly high beta-diversity (Sorensen's dissimilarity = 0.581), with samples clustering according to biome/elevation. Highly relevant considering the local scale of the study, beta-diversity had a high contribution of species replacement among locales (54.8%) and between biomes (79.6%), suggesting environmental heterogeneity as the dominant force shaping diversity at such small scale, directly and indirectly on the plant communities. Protection actions in the Park, especially these addressed at the imperative conservation of dry forest, must ponder the small scale at which processes shape species diversity and community structure for inconspicuous, yet extraordinarily diverse organisms such as the leaf beetles. PMID- 27276229 TI - Repeated and Widespread Evolution of Bioluminescence in Marine Fishes. AB - Bioluminescence is primarily a marine phenomenon with 80% of metazoan bioluminescent genera occurring in the world's oceans. Here we show that bioluminescence has evolved repeatedly and is phylogenetically widespread across ray-finned fishes. We recover 27 independent evolutionary events of bioluminescence, all among marine fish lineages. This finding indicates that bioluminescence has evolved many more times than previously hypothesized across fishes and the tree of life. Our exploration of the macroevolutionary patterns of bioluminescent lineages indicates that the present day diversity of some inshore and deep-sea bioluminescent fish lineages that use bioluminescence for communication, feeding, and reproduction exhibit exceptional species richness given clade age. We show that exceptional species richness occurs particularly in deep-sea fishes with intrinsic bioluminescent systems and both shallow water and deep-sea lineages with luminescent systems used for communication. PMID- 27276230 TI - Contribution of hepatic cytochrome CYP1A and metallothionein mRNA abundance to biomonitoring-A case study with European flounder (Platichthys flesus) from the Gulf of Gdansk. AB - The aim of the research was to explore the contribution of hepatic cytochrome CYP1A and metallothionein (MT) mRNA expression to biological effect monitoring. The study was conducted in the European flounder (Platichthys flesus) from the Gulf of Gdansk. mRNA abundance was measured using reverse transcriptase polymerase chain reaction (RT-PCR) in liver RNA of fish sampled from three coastal stations and from one offshore station in the inner Gulf. The contribution of the mRNA-based biomarkers to the assessment of the environment was determined in conjunction with a selection of commonly applied biochemical markers: 7-ethoxyresorufin-O-deethylase (EROD), glutathione-S-transferase (GST), catalase (CAT), metallothioneins (MT), fluorescent aromatic compounds (FACs), all measured in the same individual fish. The mRNA biomarkers contributed to the separation between the sampling sites, but no correlations between CYP1A mRNA and EROD nor between MT mRNA and MT proteins were found, which should be attributed to the different levels these biomarkers correspond to and to the differences in factors that may affect them. One case of strong correlation between CYP1A mRNA and FACs was encountered. The overall results of this study suggest that biomarkers measured at the mRNA abundance level constitute a valuable addition to biomonitoring studies by providing additional information and contributing to the differentiation of results. PMID- 27276231 TI - A Novel Peptide Hydrogel for an Antimicrobial Bandage Contact Lens. AB - A peptide hydrogel with an antimicrobial activity is developed as a bandage contact lens. The antimicrobial activity is enhanced with the addition of the biomolecules penicillin G or poly-epsilon-lysine and is positive against Staphylococcus aureus and Escherichia coli. The lens is also noncytotoxic toward a human corneal epithelial cell line and as a consequence is of great potential as a drug-eluting bandage lens replacing conventional corneal ulcer treatment. PMID- 27276232 TI - Therapeutic role of a synthesized calcium phosphate nanocomposite material on hepatocarcinogenesis in rats. AB - Nanotechnology research is booming worldwide, and the general belief is that medical and biological applications will form the greatest sector of expansion over the next decade. With this in mind, this study was designed to evaluate the therapeutic effects of a synthesized tricalcium phosphate nanocomposite material (nano-TCP) on hepatocarcinoma in a rat model, as initiated with diethylnitrosamine (DEN) and promoted with phenobarbital (PB). Hepatocarcinoma was induced with intraperitoneal injections of DEN (50 mg.(kg body mass)(-1)) 3 times a week for 2 weeks. Three weeks after the last dose of DEN, the rats received PB (0.05 %, w/v) in their drinking water for a further 6 weeks. Nano-TCP (100 mg.(kg body mass)(-1)) was administered intraperitoneally 3 times per week to rats with HCC. At the end of the experimental period, liver samples were collected from all animals for biochemical and histopathological analysis. The degree of DNA fragmentation was analyzed, in addition to immune status, by measuring the levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2). The activities of the most important free radical scavengers of the antioxidant defense system as well as malondialdehyde (MDA) content and liver enzymes were measured. The levels of hepatic heat shock protein-70 (HSP-70), caspase-3, and metalloproteinase-9 were also measured as markers for inflammation and apoptosis. Histopathological examination of liver tissue was performed. The results revealed the potent efficacy of nano-TCP in repairing the fragmented DNA and ameliorating most of the investigated parameters by significant elevation in the levels of hepatic alanine aminotransferase (ALT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. On the other hand, there was a significant decrease in hepatic gamma-glutamyl transpeptidase (gamma-GT), MDA, IL-2, IFN-gamma, TNF-alpha, matrix metalloproteinase-9 (MMP-9), HSP-70, and caspase-3 levels upon treatment. The findings form histopathological examination of the liver tissues agreed with the biochemical results and confirmed the difference between the control and treatment groups. In conclusion, nano-TCP succeeded in treating hepatocarcinoma efficiently, and presents a new hope for patients to get safe, fast, and effective treatment. PMID- 27276233 TI - Organophosphorus Compounds in Organic Electronics. AB - This Minireview describes recent advances of organophosphorus compounds as opto electronic materials in the field of organic electronics. The progress of (hetero ) phospholes, unsaturated phosphanes, and trivalent and pentavalent phosphanes since 2010 is covered. The described applications of organophosphorus materials range from single molecule sensors, field effect transistors, organic light emitting diodes, to polymeric materials for organic photovoltaic applications. PMID- 27276236 TI - Iodide-Catalyzed Synthesis of Secondary Thiocarbamates from Isocyanides and Thiosulfonates. AB - A new method for the synthesis of secondary thiocarbamates from readily available isocyanides and thiosulfonates with broad functional group tolerance is reported. The reaction proceeds under mild reaction conditions in isopropanol and is catalyzed by inexpensive sodium iodide. PMID- 27276235 TI - Nickel-Catalyzed Asymmetric Kumada Cross-Coupling of Symmetric Cyclic Sulfates. AB - Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate. PMID- 27276238 TI - Interassociation Task Force Punts Decision on Universal ECG Screenings for Athletes. PMID- 27276237 TI - Self-Assembly of Complex DNA Tessellations by Using Low-Symmetry Multi-arm DNA Tiles. AB - Modular DNA tile-based self-assembly is a versatile way to engineer basic tessellation patterns on the nanometer scale, but it remains challenging to achieve high levels of structural complexity. We introduce a set of general design principles to create intricate DNA tessellations by employing multi-arm DNA motifs with low symmetry. We achieved two novel Archimedean tiling patterns, (4.8.8) and (3.6.3.6), and one pattern with higher-order structures beyond the complexity observed in Archimedean tiling. Our success in assembling complicated DNA tessellations demonstrates the broad design space of DNA structural motifs, enriching the toolbox of DNA tile-based self-assembly and expanding the complexity boundaries of DNA tile-based tessellation. PMID- 27276239 TI - Metalloporphines: Dimers and Trimers. AB - Procedures for the purification and subsequent crystallization of the slightly soluble four-coordinate metallporphines, the simplest possible porphyrin derivatives, are described. Crystals of the porphine derivatives of cobalt(II), copper(II), platinum(II), and two polymorphs of zinc(II) were obtained. Analysis of the crystal and molecular structures shows that all except the platinum(II) derivative form an unusual trimeric species in the solid state. The isomorphous cobalt(II), copper(II), and one zinc(II) polymorph pack in the unit cell to form dimers as well as the trimers. Interplanar spacings between porphine rings are similar in both the dimers and trimers and range between 3.24 and 3.37 A. Porphine rings are strongly overlapped with lateral shifts between ring centers in both the dimers and trimers with values between 1.52 and 1.70 A or in Category S as originally defined by Scheidt and Lee. Periodic trends in the M-Np bond distances parallel those observed previously for tetraphenyl- and octaethylporphyrin derivatives. PMID- 27276240 TI - Renal Leiomyoma and Leiomyosarcoma: A Study of 57 Cases. AB - Primary renal leiomyomas and leiomyosarcomas are rare, and there is a paucity of data regarding the pathologic features and outcomes of patients with these tumors. The objective of this study was to review a large series of renal smooth muscle tumors, in order to more fully elucidate their natural histories. Fifty seven renal smooth muscle tumors were reviewed for various histopathologic features, and leiomyosarcomas were graded using the French Federation of Cancer Centers (FNCLCC) system. Tumor cores in tissue microarrays were evaluated for smooth muscle actin, desmin, h-caldesmon, calponin, myogenin, cytokeratin (OSCAR), CD117, Ki67, estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor 1 (WT1). Leiomyomas were selected on the basis of preexisting diagnostic criteria, which included a lack of cytologic atypia, necrosis, and mitotic activity (0 to 1 mitoses/10 hpf). These were found to have a strong predilection for women, tended to arise from the renal capsule, were small (mean size, 4.2 cm), and had a low Ki67 proliferative rate (mean 1.4%). In addition, they uniformly expressed all smooth muscle markers and were ER/PR/WT1 positive in nearly all cases. In 10 patients with clinical follow-up, none had a tumor recurrence. In contrast, leiomyosarcomas had an equal sex distribution, were larger (mean size, 9.8 cm), had significantly higher mitotic activity (mean 8.6 mitoses/10 hpf), with most being FNCLCC grade 2. Leiomyosarcomas expressed at least 1 muscle marker, higher Ki67 proliferative activity (mean 20.4%) than leiomyomas, and most were ER/PR/WT1 negative. Tumor recurrence occurred in 65% of patients, and 35% of patients died of disease. This study therefore validates existing criteria to distinguish between leiomyomas and leiomyosarcomas. PMID- 27276241 TI - Serious adverse drug events related to non-investigational drugs in academic clinical trials: another source of safety data for risk assessment? AB - AIMS: Sponsors of clinical trials have to analyze serious adverse events (SAEs). Both sponsors and investigators determine the relationship between the investigational medicinal product, the investigational device or procedure and SAEs. SAEs related to another cause, such as a non-investigational medicinal product (NIMP), do not have clear pharmacovigilance reporting requirements. The aim of this study was to evaluate the amount and the nature of NIMP-related SAEs recorded by three French academic sponsors and to propose pharmacovigilance requirements for these cases. METHODS: This was a retrospective descriptive study including all cases of NIMP-related SAEs occurring in clinical trials and reported to three academic sponsors between January 2009 and October 2014. RESULTS: Among 5870 cases of SAEs, 300 (5%) were related to a NIMP in 50 clinical trials. Involved NIMPs were mainly antithrombotics, cytostatics and immunosuppressants. Some of these drugs were currently followed by a risk management plan (e.g. rivoxaban). The most frequent NIMP-related SAEs were neurological, gastrointestinal and infectious disorders. Seven NIMP-related SAEs were known as 'rare' or 'very rare' and two were 'unlabelled'. CONCLUSIONS: As far as we know, this is the first study to focus about NIMP-related SAEs occurring in clinical trials. This work highlights the potential high quality source of safety data via NIMP-related SAE collection. Globally, we propose that NIMP-related SAEs occurring in clinical trials should systematically be notified to the pharmacovigilance system of the concerned country. Clearer procedures of interactions between safety units of academic sponsors and pharmacovigilance systems are needed to allow an effective recording of NIMP-related SAEs. PMID- 27276243 TI - Hepatic Gadolinium Deposition and Reversibility after Contrast Agent-enhanced MR Imaging of Pediatric Hematopoietic Stem Cell Transplant Recipients. AB - Purpose To determine if hepatic gadolinium deposition occurs in pediatric patients with iron overload but normal renal and hepatic function who undergo gadolinium-based contrast agent (GBCA)-enhanced magnetic resonance (MR) imaging. Materials and Methods Design and execution of this study was approved by the Ethical Committee of Institute for Research in Maternal and Child Health Burlo Garofolo of Trieste (reference no. 1105/2015). Because of the retrospective nature of the study, the requirement to obtain informed consent was waived. Twenty-one recipients of allogeneic hematopoietic stem cell transplants who underwent GBCA-enhanced MR imaging for suspected infection or relapse followed by liver biopsy comprised the study group. The number of GBCA-enhanced MR examinations and cumulative gadolinium dose for each patient was analyzed by comparing liver histologic analysis and iron and gadolinium liver concentration (GLC). Eight patients had siderosis and underwent chelation therapy. The study group was compared with four control patients who were never exposed to GBCA. Statistical analysis was performed with Spearman rank coefficient for correlation. Results All 21 patients had positive correlations between GLC and total GBCA dose (r = 0.4486; P < .05) and between GLC and liver iron concentration (r = 0.56; P < .05). Patients who underwent deferoxamine therapy had a significant reduction of GLC (from 0.64 MUg/g +/- 0.29 to 0.20 MUg/g +/- 0.17 [standard deviation]; P < .05). Conclusion In the presence of siderosis, a transmetallation mechanism may be set off between ferric ion and gadoterate meglumine. Deferoxamine appears capable of binding to gadolinium ion. Further studies of the safety of GBCAs in severe siderosis are needed. Chelation should be considered in patients with iron overload and a history of GBCA exposure. (c) RSNA, 2016. PMID- 27276242 TI - Assessing the Stability of Aortic Aneurysms with Pulse Wave Imaging. AB - Purpose To assess whether the stability of murine aortic aneurysms is associated with the homogeneity of pulse wave propagation within the saccular wall. Materials and Methods All animal procedures were approved by the institutional Animal Care and Use Committee. Apolipoprotein E and tissue inhibitor of metalloproteinases-1 knockout mice (n = 26) were infused with angiotensin II by using subcutaneously implanted osmotic pumps, with an additional control mouse used for histologic examination (n = 1). Pulse wave imaging (PWI) was performed just before infusion and 15 days after infusion by using 40-MHz ultrasonography at 8000 frames per second (with electrocardiographic gating). Aneurysm appearance on B-mode images was monitored every 2-3 days for 30 days. On the basis of B-mode images obtained after 30 days, aneurysms were deemed to have been unstable if they had ruptured; otherwise, they were deemed stable. Statistical significance was assessed by using two-tailed t tests. Results In normal aortas, the pulse waves propagated at relatively constant velocities (mean +/- standard deviation, 2.8 m/sec +/- 0.9). Fifteen days after infusion, all mice had developed aneurysms, with significant (P < .001/12) changes in maximum anterior-posterior diameter (increase of 54.9% +/- 2.5) and pulse wave velocity (PWV) (decrease of 1.3 m/sec +/- 0.8). While there was no significant difference in these parameters (P = .45 for diameter and P = .55 for PWV) between stable aneurysms (n = 12) and unstable aneurysms (n = 14), the standard deviation of the high-resolution PWV was significantly higher (P < .001/12) in unstable aneurysms (5.7 m/sec +/- 1.6) than in stable ones (3.2 m/sec +/- 0.9). Conclusion High-resolution PWI was used to measure the local homogeneity of pulse wave propagation within the saccular wall, which is lower in unstable aneurysms than in stable ones. Hence, if proven to add additional information beyond size and appearance in human studies, PWI could potentially be used to assess the stability of aneurysms by providing information that is complementary to the anatomic data obtained with conventional B-mode imaging. (c) RSNA, 2016 Online supplemental material is available for this article. PMID- 27276244 TI - Aldehyde dehydrogenase 3A1 promotes multi-modality resistance and alters gene expression profile in human breast adenocarcinoma MCF-7 cells. AB - Aldehyde dehydrogenases participate in a variety of cellular homeostatic mechanisms like metabolism, proliferation, differentiation, apoptosis, whereas recently, they have been implicated in normal and cancer cell stemness. We explored roles for ALDH3A1 in conferring resistance to chemotherapeutics/radiation/oxidative stress and whether ectopic overexpression of ALDH3A1 could lead to alterations of gene expression profile associated with cancer stem cell-like phenotype. MCF-7 cells were stably transfected either with an empty vector (mock) or human aldehyde dehydrogenase 3A1 cDNA. The expression of aldehyde dehydrogenase 3A1 in MCF-7 cells was associated with altered cell proliferation rate and enhanced cell resistance against various chemotherapeutic drugs (4-hydroxyperoxycyclophosphamide, doxorubicin, etoposide, and 5 fluorouracil). Aldehyde dehydrogenase 3A1 expression also led to increased tolerance of MCF-7 cells to gamma radiation and hydrogen peroxide-induced stress. Furthermore, aldehyde dehydrogenase 3A1-expressing MCF-7 cells exhibited gene up regulation of cyclins A, B1, B2, and down-regulation of cyclin D1 as well as transcription factors p21, CXR4, Notch1, SOX2, SOX4, OCT4, and JAG1. When compared to mock cells, no changes were observed in mRNA levels of ABCA2 and ABCB1 protein pumps with only a minor decrease of the ABCG2 pump in the aldehyde dehydrogenase 3A1-expressing cells. Also, the adhesion molecules EpCAM and CD49F were also found to be up-regulated in aldehyde dehydrogenase 3A1expressing cells. Taken together, ALDH3A1 confers a multi-modality resistance phenotype in MCF-7 cells associated with slower growth rate, increased clonogenic capacity, and altered gene expression profile, underlining its significance in cell homeostasis. PMID- 27276245 TI - STAT5a promotes the transcription of mature mmu-miR-135a in 3T3-L1 cells by binding to both miR-135a-1 and miR-135a-2 promoter elements. AB - Despite extensive research on the role of miR-135a in biological processes, very little attention has been paid to the regulation of its transcription. We have previously reported that miR-135a suppresses 3T3-L1 preadipocyte differentiation and adipogenesis by directly targeting the adenomatous polyposis coli (APC) gene and activating the canonical Wnt/beta-catenin signaling pathway, but the regulatory elements that regulate the expression of the two isoforms of miR-135a (miR-135a-1 and miR-135a-2) remain poorly understood. Here, by using deletion analysis, we predicted two binding sites (-874/-856 and -2020/-2002) for the transcription factor Signal Transducers and Activators of Transcription 5a (STAT5a) within the core promoters of miR-135a-1 and miR-135a-2 (-1128/-556 and 2264/-1773), and the subsequent site-directed mutagenesis indicated that the two STAT5a binding sites regulated the activity of the miR-135a-1 and miR-135a-2 promoters. The binding of STAT5a to the miR-135a-1/2 core promoters in vitro and in cell culture was identified by electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays. Overexpression and RNAi knockdown of STAT5a showed that the transcription factor regulated the endogenous miR-135a expression. Additionally, The expression time frame of STAT5a and APC indicated a potential negative feedback between them. In sum, the overall results from this study indicate that STAT5a regulates miR-135a transcription by binding to both miR-135a-1 and miR135a-2 promoter elements and the findings provide novel insights into the molecular regulatory mechanisms of miR-135a during adipogenesis. PMID- 27276246 TI - Ensemble View of RNAs and Proteins: Loops, Knots, Territories, and Evolution. PMID- 27276234 TI - Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. AB - BACKGROUND: Limited data are available to guide the choice of a target for the systolic blood-pressure level when treating acute hypertensive response in patients with intracerebral hemorrhage. METHODS: We randomly assigned eligible participants with intracerebral hemorrhage (volume, <60 cm(3)) and a Glasgow Coma Scale (GCS) score of 5 or more (on a scale from 3 to 15, with lower scores indicating worse condition) to a systolic blood-pressure target of 110 to 139 mm Hg (intensive treatment) or a target of 140 to 179 mm Hg (standard treatment) in order to test the superiority of intensive reduction of systolic blood pressure to standard reduction; intravenous nicardipine to lower blood pressure was administered within 4.5 hours after symptom onset. The primary outcome was death or disability (modified Rankin scale score of 4 to 6, on a scale ranging from 0 [no symptoms] to 6 [death]) at 3 months after randomization, as ascertained by an investigator who was unaware of the treatment assignments. RESULTS: Among 1000 participants with a mean (+/-SD) systolic blood pressure of 200.6+/-27.0 mm Hg at baseline, 500 were assigned to intensive treatment and 500 to standard treatment. The mean age of the patients was 61.9 years, and 56.2% were Asian. Enrollment was stopped because of futility after a prespecified interim analysis. The primary outcome of death or disability was observed in 38.7% of the participants (186 of 481) in the intensive-treatment group and in 37.7% (181 of 480) in the standard treatment group (relative risk, 1.04; 95% confidence interval, 0.85 to 1.27; analysis was adjusted for age, initial GCS score, and presence or absence of intraventricular hemorrhage). Serious adverse events occurring within 72 hours after randomization that were considered by the site investigator to be related to treatment were reported in 1.6% of the patients in the intensive-treatment group and in 1.2% of those in the standard-treatment group. The rate of renal adverse events within 7 days after randomization was significantly higher in the intensive-treatment group than in the standard-treatment group (9.0% vs. 4.0%, P=0.002). CONCLUSIONS: The treatment of participants with intracerebral hemorrhage to achieve a target systolic blood pressure of 110 to 139 mm Hg did not result in a lower rate of death or disability than standard reduction to a target of 140 to 179 mm Hg. (Funded by the National Institute of Neurological Disorders and Stroke and the National Cerebral and Cardiovascular Center; ATACH-2 ClinicalTrials.gov number, NCT01176565 .). PMID- 27276247 TI - Heterogeneous Epitaxy: Designed Peptides Scale Graphene's Surface. PMID- 27276248 TI - Modulation of the pH Stability of Influenza Virus Hemagglutinin: A Host Cell Adaptation Strategy. AB - Proteins undergo dynamic structural changes to function within the range of physical and chemical conditions of their microenvironments. Changes in these environments affect their activity unless the respective mutations preserve their proper function. Here, we examine the influenza A virus spike protein hemagglutinin (HA), which undergoes a dynamic conformational change that is essential to the viral life cycle and is dependent on endosomal pH. Since the cells of different potential hosts exhibit different levels of pH, the virus can only cross species barriers if HA undergoes mutations that still permit the structural change to occur. This key event occurs after influenza A enters the host cell via the endocytic route, during its intracellular transport inside endosomes. The acidic pH inside these vesicles triggers a major structural transition of HA that induces fusion of the viral envelope and the endosomal membrane, and permits the release of the viral genome. HA experiences specific mutations that alter its pH stability and allow the conformational changes required for fusion in different hosts, despite the differences in the degree of acidification of their endosomes. Experimental and theoretical studies over the past few years have provided detailed insights into the structural aspects of the mutational changes that alter its susceptibility to different pH thresholds. We will illustrate how such mutations modify the protein's structure and consequently its pH stability. These changes make HA an excellent model of the way subtle structural modifications affect a protein's stability and enable it to function in diverse environments. PMID- 27276249 TI - Correlation among DNA Linker Length, Linker Histone Concentration, and Histone Tails in Chromatin. AB - Eukaryotic cells condense their genetic material in the nucleus in the form of chromatin, a macromolecular complex made of DNA and multiple proteins. The structure of chromatin is intimately connected to the regulation of all eukaryotic organisms, from amoebas to humans, but its organization remains largely unknown. The nucleosome repeat length (NRL) and the concentration of linker histones (rhoLH) are two structural parameters that vary among cell types and cell cycles; the NRL is the number of DNA basepairs wound around each nucleosome core plus the number of basepairs linking successive nucleosomes. Recent studies have found a linear empirical relationship between the variation of these two properties for different cells, but its underlying mechanism remains elusive. Here we apply our established mesoscale chromatin model to explore the mechanisms responsible for this relationship, by investigating chromatin fibers as a function of NRL and rhoLH combinations. We find that a threshold of linker histone concentration triggers the compaction of chromatin into well-formed 30-nm fibers; this critical value increases linearly with NRL, except for long NRLs, where the fibers remain disorganized. Remarkably, the interaction patterns between core histone tails and chromatin elements are highly sensitive to the NRL and rhoLH combination, suggesting a molecular mechanism that could have a key role in regulating the structural state of the fibers in the cell. An estimate of the minimized work and volume associated with storage of chromatin fibers in the nucleus further suggests factors that could spontaneously regulate the NRL as a function of linker histone concentration. Both the tail interaction map and DNA packing considerations support the empirical NRL/rhoLH relationship and offer a framework to interpret experiments for different chromatin conditions in the cell. PMID- 27276250 TI - Contact Statistics Highlight Distinct Organizing Principles of Proteins and RNA. AB - Although both RNA and proteins have densely packed native structures, chain organizations of these two biopolymers are fundamentally different. Motivated by the recent discoveries in chromatin folding that interphase chromosomes have territorial organization with signatures pointing to metastability, we analyzed the biomolecular structures deposited in the Protein Data Bank and found that the intrachain contact probabilities, P(s) as a function of the arc length s, decay in power-law ~s(-gamma) over the intermediate range of s, 10 ? s ? 110. We found that the contact probability scaling exponent is gamma ~ 1.11 for large RNA (N > 110), gamma ~ 1.41 for small-sized RNA (N < 110), and gamma ~ 1.65 for proteins. Given that Gaussian statistics is expected for a fully equilibrated chain in polymer melts, the deviation of gamma-value from gamma = 1.5 for the subchains of large RNA in the native state suggests that the chain configuration of RNA is not fully equilibrated. It is visually clear that folded structures of large-sized RNA (N ? 110) adopt crumpled structures, partitioned into modular multidomains assembled by proximal sequences along the chain, whereas the polypeptide chain of folded proteins looks better mixed with the rest of the structure. Our finding of gamma ~ 1 for large RNA might be an ineluctable consequence of the hierarchical ordering of the secondary to tertiary elements in the folding process. PMID- 27276252 TI - Structure of the Bacterial Cytoskeleton Protein Bactofilin by NMR Chemical Shifts and Sequence Variation. AB - Bactofilins constitute a recently discovered class of bacterial proteins that form cytoskeletal filaments. They share a highly conserved domain (DUF583) of which the structure remains unknown, in part due to the large size and noncrystalline nature of the filaments. Here, we describe the atomic structure of a bactofilin domain from Caulobacter crescentus. To determine the structure, we developed an approach that combines a biophysical model for proteins with recently obtained solid-state NMR spectroscopy data and amino acid contacts predicted from a detailed analysis of the evolutionary history of bactofilins. Our structure reveals a triangular beta-helical (solenoid) conformation with conserved residues forming the tightly packed core and polar residues lining the surface. The repetitive structure explains the presence of internal repeats as well as strongly conserved positions, and is reminiscent of other fibrillar proteins. Our work provides a structural basis for future studies of bactofilin biology and for designing molecules that target them, as well as a starting point for determining the organization of the entire bactofilin filament. Finally, our approach presents new avenues for determining structures that are difficult to obtain by traditional means. PMID- 27276251 TI - Influence of Glu/Arg, Asp/Arg, and Glu/Lys Salt Bridges on alpha-Helical Stability and Folding Kinetics. AB - Using a combination of ultraviolet circular dichroism, temperature-jump transient infrared spectroscopy, and molecular dynamics simulations, we investigate the effect of salt bridges between different types of charged amino-acid residue pairs on alpha-helix folding. We determine the stability and the folding and unfolding rates of 12 alanine-based alpha-helical peptides, each of which has a nearly identical composition containing three pairs of positively and negatively charged residues (either Glu(-)/Arg(+), Asp(-)/Arg(+), or Glu(-)/Lys(+)). Within each set of peptides, the distance and order of the oppositely charged residues in the peptide sequence differ, such that they have different capabilities of forming salt bridges. Our results indicate that stabilizing salt bridges (in which the interacting residues are spaced and ordered such that they favor helix formation) speed up alpha-helix formation by up to 50% and slow down the unfolding of the alpha-helix, whereas salt bridges with an unfavorable geometry have the opposite effect. Comparing the peptides with different types of charge pairs, we observe that salt bridges between side chains of Glu(-) and Arg(+) are most favorable for the speed of folding, probably because of the larger conformational space of the salt-bridging Glu(-)/Arg(+) rotamer pairs compared to Asp(-)/Arg(+) and Glu(-)/Lys(+). We speculate that the observed impact of salt bridges on the folding kinetics might explain why some proteins contain salt bridges that do not stabilize the final, folded conformation. PMID- 27276253 TI - Three-Dimensional Domain Swapping Changes the Folding Mechanism of the Forkhead Domain of FoxP1. AB - The forkhead family of transcription factors (Fox) controls gene transcription during key processes such as regulation of metabolism, embryogenesis, and immunity. Structurally, Fox proteins feature a conserved DNA-binding domain known as forkhead. Interestingly, solved forkhead structures of members from the P subfamily (FoxP) show that they can oligomerize by three-dimensional domain swapping, whereby structural elements are exchanged between adjacent subunits, leading to an intertwined dimer. Recent evidence has largely stressed the biological relevance of domain swapping in FoxP, as several disease-causing mutations have been related to impairment of this process. Here, we explore the equilibrium folding and binding mechanism of the forkhead domain of wild-type FoxP1, and of two mutants that hinder DNA-binding (R53H) and domain swapping (A39P), using size-exclusion chromatography, circular dichroism, and hydrogen deuterium exchange mass spectrometry. Our results show that domain swapping of FoxP1 occurs at micromolar protein concentrations within hours of incubation and is energetically favored, in contrast to classical domain-swapping proteins. Also, DNA-binding mutations do not significantly affect domain swapping. Remarkably, equilibrium unfolding of dimeric FoxP1 follows a three-state N2 <-> 2I <-> 2U folding mechanism in which dimer dissociation into a monomeric intermediate precedes protein unfolding, in contrast to the typical two-state model described for most domain-swapping proteins, whereas the A39P mutant follows a two-state N <-> U folding mechanism consistent with the second transition observed for dimeric FoxP1. Also, the free-energy change of the N <-> U in A39P FoxP1 is ~2 kcal?mol(-1) larger than the I <-> U transition of both wild-type and R53H FoxP1. Finally, hydrogen-deuterium exchange mass spectrometry reveals that the intermediate strongly resembles the native state. Our results suggest that domain swapping in FoxP1 is at least partially linked to monomer folding stability and follows an unusual three-state folding mechanism, which might proceed via transient structural changes rather than requiring complete protein unfolding as do most domain-swapping proteins. PMID- 27276254 TI - Sequence Context Influences the Structure and Aggregation Behavior of a PolyQ Tract. AB - Expansions of polyglutamine (polyQ) tracts in nine different proteins cause a family of neurodegenerative disorders called polyQ diseases. Because polyQ tracts are potential therapeutic targets for these pathologies there is great interest in characterizing the conformations that they adopt and in understanding how their aggregation behavior is influenced by the sequences flanking them. We used solution NMR to study at single-residue resolution a 156-residue proteolytic fragment of the androgen receptor that contains a polyQ tract associated with the disease spinobulbar muscular atrophy, also known as Kennedy disease. Our findings indicate that a Leu-rich region preceding the polyQ tract causes it to become alpha-helical and appears to protect the protein against aggregation, which represents a new, to our knowledge, mechanism by which sequence context can minimize the deleterious properties of these repetitive regions. Our results have implications for drug discovery for polyQ diseases because they suggest that the residues flanking these repetitive sequences may represent viable therapeutic targets. PMID- 27276255 TI - A Simple Model of Protein Domain Swapping in Crowded Cellular Environments. AB - Domain swapping in proteins is an important mechanism of functional and structural innovation. However, despite its ubiquity and importance, the physical mechanisms that lead to domain swapping are poorly understood. Here, we present a simple two-dimensional coarse-grained model of protein domain swapping in the cytoplasm. In our model, two-domain proteins partially unfold and diffuse in continuous space. Monte Carlo multiprotein simulations of the model reveal that domain swapping occurs at intermediate temperatures, whereas folded dimers and folded monomers prevail at low temperatures, and partially unfolded monomers predominate at high temperatures. We use a simplified amino acid alphabet consisting of four residue types, and find that the oligomeric state at a given temperature depends on the sequence of the protein. We also show that hinge strain between domains can promote domain swapping, consistent with experimental observations for real proteins. Domain swapping depends nonmonotonically on the protein concentration, with domain-swapped dimers occurring at intermediate concentrations and nonspecific interactions between partially unfolded proteins occurring at high concentrations. For folded proteins, we recover the result obtained in three-dimensional lattice simulations, i.e., that functional dimerization is most prevalent at intermediate temperatures and nonspecific interactions increase at low temperatures. PMID- 27276256 TI - Chaperonin TRiC/CCT Recognizes Fusion Oncoprotein AML1-ETO through Subunit Specific Interactions. AB - AML1-ETO is the translational product of a chimeric gene created by the stable chromosome translocation t (8;21)(q22;q22). It causes acute myeloid leukemia (AML) by dysregulating the expression of genes critical for myeloid cell development and differentiation and recently has been reported to bind multiple subunits of the mammalian cytosolic chaperonin TRiC (or CCT), primarily through its DNA binding domain (AML1-175). Through these interactions, TRiC plays an important role in the synthesis, folding, and activity of AML1-ETO. Using single particle cryo-electron microscopy, we demonstrate here that a folding intermediate of AML1-ETO's DNA-binding domain (AML1-175) forms a stable complex with apo-TRiC. Our structure reveals that AML1-175 associates directly with a specific subset of TRiC subunits in the open conformation. PMID- 27276257 TI - Oxidation of RyR2 Has a Biphasic Effect on the Threshold for Store Overload Induced Calcium Release. AB - At the single-channel level, oxidation of the cardiac ryanodine receptor (RyR2) is known to activate and inhibit the channel depending on the level of oxidation. However, the mechanisms through which these changes alter the activity of RyR2 in a cellular setting are poorly understood. In this study, we determined the effect of oxidation on a common form of RyR2 regulation; store overload-induced Ca(2+) release (SOICR). We found that oxidation resulted in concentration and time dependent changes in the activation threshold for SOICR. Low concentrations of the oxidant H2O2 resulted in a decrease in the threshold for SOICR, which led to an increase in SOICR events. However, higher concentrations of H2O2, or prolonged exposure, reversed these changes and led to an increase in the threshold for SOICR. This increase in the threshold for SOICR in most cells was to such an extent that it led to the complete inhibition of SOICR. Acute exposure to high concentrations of H2O2 led to an initial decrease and then increase in the threshold for SOICR. In the majority of cells the increased threshold could not be reversed by the application of the reducing agent dithiothreitol. Therefore, our data suggest that low levels of RyR2 oxidation increase the channel activity by decreasing the threshold for SOICR, whereas high levels of RyR2 oxidation irreversibly increase the threshold for SOICR leading to an inhibition of RyR2. Combined, this indicates that oxidation regulates RyR2 by the same mechanism as phosphorylation, methylxanthines, and mutations, via changes in the threshold for SOICR. PMID- 27276258 TI - Enthalpy-Entropy Compensation in the Binding of Modulators at Ionotropic Glutamate Receptor GluA2. AB - The 1,2,4-benzothiadiazine 1,1-dioxide type of positive allosteric modulators of the ionotropic glutamate receptor A2 (GluA2) are promising lead compounds for the treatment of cognitive disorders, e.g., Alzheimer's disease. The modulators bind in a cleft formed by the interface of two neighboring ligand binding domains and act by stabilizing the agonist-bound open-channel conformation. The driving forces behind the binding of these modulators can be significantly altered with only minor substitutions to the parent molecules. In this study, we show that changing the 7-fluorine substituent of modulators BPAM97 (2) and BPAM344 (3) into a hydroxyl group (BPAM557 (4) and BPAM521 (5), respectively), leads to a more favorable binding enthalpy (DeltaH, kcal/mol) from -4.9 (2) and -7.5 (3) to -6.2 (4) and -14.5 (5), but also a less favorable binding entropy (-TDeltaS, kcal/mol) from -2.3 (2) and -1.3 (3) to -0.5 (4) and 4.8 (5). Thus, the dissociation constants (Kd, MUM) of 4 (11.2) and 5 (0.16) are similar to those of 2 (5.6) and 3 (0.35). Functionally, 4 and 5 potentiated responses of 10 MUM L-glutamate at homomeric rat GluA2(Q)i receptors with EC50 values of 67.3 and 2.45 MUM, respectively. The binding mode of 5 was examined with x-ray crystallography, showing that the only change compared to that of earlier compounds was the orientation of Ser-497 pointing toward the hydroxyl group of 5. The favorable enthalpy can be explained by the formation of a hydrogen bond from the side-chain hydroxyl group of Ser-497 to the hydroxyl group of 5, whereas the unfavorable entropy might be due to desolvation effects combined with a conformational restriction of Ser-497 and 5. In summary, this study shows a remarkable example of enthalpy-entropy compensation in drug development accompanied with a likely explanation of the underlying structural mechanism. PMID- 27276260 TI - Patch-Clamp Study of Hepatitis C p7 Channels Reveals Genotype-Specific Sensitivity to Inhibitors. AB - Hepatitis C is a major worldwide disease and health hazard, affecting ~3% of the world population. The p7 protein of hepatitis C virus (HCV) is an intracellular ion channel and pH regulator that is involved in the viral replication cycle. It is targeted by various classical ion channel blockers. Here, we generated p7 constructs corresponding to HCV genotypes 1a, 2a, 3a, and 4a for recombinant expression in HEK293 cells, and studied p7 channels using patch-clamp recording techniques. The pH50 values for recombinant p7 channels were between 6.0 and 6.5, as expected for proton-activated channels, and current-voltage dependence did not show any differences between genotypes. Inhibition of p7-mediated currents by amantadine, however, exhibited significant, genotype-specific variation. The IC50 values of p7-1a and p7-4a were 0.7 +/- 0.1 nM and 3.2 +/- 1.2 nM, whereas p7-2a and p7-3a had 50- to 1000-fold lower sensitivity, with IC50 values of 2402 +/- 334 nM and 344 +/- 64 nM, respectively. The IC50 values for rimantadine were low across all genotypes, ranging from 0.7 +/- 0.1 nM, 1.6 +/- 0.6 nM, and 3.0 +/- 0.8 nM for p7-1a, p7-3a, and p7-4a, respectively, to 24 +/- 4 nM for p7-2a. Results from patch-clamp recordings agreed well with cellular assays of p7 activity, namely, measurements of intracellular pH and hemadsorption assays, which confirmed the much reduced amantadine sensitivity of genotypes 2a and 3a. Thus, our results establish patch-clamp studies of recombinant viroporins as a valid analytical tool that can provide quantitative information about viroporin channel properties, complementing established techniques. PMID- 27276259 TI - Release of Entropic Spring Reveals Conformational Coupling Mechanism in the ABC Transporter BtuCD-F. AB - Substrate translocation by ATP-binding cassette (ABC) transporters involves coupling of ATP binding and hydrolysis in the nucleotide-binding domains (NBDs) to conformational changes in the transmembrane domains. We used molecular dynamics simulations to investigate the atomic-level mechanism of conformational coupling in the ABC transporter BtuCD-F, which imports vitamin B12 across the inner membrane of Escherichia coli. Our simulations show how an engineered disulfide bond across the NBD dimer interface reduces conformational fluctuations and hence configurational entropy. As a result, the disulfide bond is under substantial mechanical stress. Releasing this entropic spring, as is the case in the wild-type transporter, combined with analyzing the pairwise forces between individual residues, unravels the coupling mechanism. The identified pathways along which force is propagated from the NBDs via the coupling helix to the transmembrane domains are composed of highly conserved residues, underlining their functional relevance. This study not only reveals the details of conformational coupling in BtuCD-F, it also provides a promising approach to other long-range conformational couplings, e.g., in ABC exporters or other ATP driven molecular machines. PMID- 27276261 TI - Effects of Lipid Tethering in Extremophile-Inspired Membranes on H(+)/OH(-) Flux at Room Temperature. AB - This work explores the proton/hydroxide permeability (PH+/OH-) of membranes that were made of synthetic extremophile-inspired phospholipids with systematically varied structural elements. A fluorescence-based permeability assay was optimized to determine the effects on the PH+/OH- through liposome membranes with variations in the following lipid attributes: transmembrane tethering, tether length, and the presence of isoprenoid methyl groups on one or both lipid tails. All permeability assays were performed in the presence of a low concentration of valinomycin (10 nM) to prevent buildup of a membrane potential without artificially increasing the measured PH+/OH-. Surprisingly, the presence of a transmembrane tether did not impact PH+/OH- at room temperature. Among tethered lipid monolayers, PH+/OH- increased with increasing tether length if the number of carbons in the untethered acyl tail was constant. Untethered lipids with two isoprenoid methyl tails led to lower PH+/OH- values than lipids with only one or no isoprenoid tails. Molecular dynamics simulations revealed a strong positive correlation between the probability of observing water molecules in the hydrophobic core of these lipid membranes and their proton permeability. We propose that water penetration as revealed by molecular dynamics may provide a general strategy for predicting proton permeability through various lipid membranes without the need for experimentation. PMID- 27276262 TI - Reorganization of Lipid Diffusion by Myelin Basic Protein as Revealed by STED Nanoscopy. AB - Myelin is a multilayered membrane that ensheathes axonal fibers in the vertebrate nervous system, allowing fast propagation of nerve action potentials. It contains densely packed lipids, lacks an actin-based cytocortex, and requires myelin basic protein (MBP) as its major structural component. This protein is the basic constituent of the proteinaceous meshwork that is localized between adjacent cytoplasmic membranes of the myelin sheath. Yet, it is not clear how MBP influences the organization and dynamics of the lipid constituents of myelin. Here, we used optical stimulated emission depletion super-resolution microscopy in combination with fluorescence correlation spectroscopy to assess the characteristics of diffusion of different fluorescent lipid analogs in myelin membrane sheets of cultured oligodendrocytes and in micrometer-sized domains that were induced by MBP in live epithelial PtK2 cells. Lipid diffusion was significantly faster and less anomalous both in oligodendrocytes and inside the MBP-rich domains of PtK2 cells compared with undisturbed live PtK2 cells. Our data show that MBP reorganizes lipid diffusion, possibly by preventing the buildup of an actin-based cytocortex and by preventing most membrane proteins from entering the myelin sheath region. Yet, in contrast to myelin sheets in oligodendrocytes, the MBP-induced domains in epithelial PtK2 cells demonstrate no change in lipid order, indicating that segregation of long-chain lipids into myelin sheets is a process specific to oligodendrocytes. PMID- 27276263 TI - The Flip-Flop Diffusion Mechanism across Lipids in a Hybrid Bilayer Membrane. AB - In this study, we examine the mechanism of flip-flop diffusion of proton carriers across the lipid layer of a hybrid bilayer membrane (HBM). The HBM consists of a lipid monolayer appended on top of a self-assembled monolayer containing a Cu based O2 reduction catalyst on a Au electrode. The flip-flop diffusion rates of the proton carriers dictate the kinetics of O2 reduction by the electrocatalyst. By varying both the tail lengths of the proton carriers and the lipids, we find the combinations of lengths that maximize the flip-flop diffusion rate. These experimental results combined with biophysical modeling studies allow us to propose a detailed mechanism for transmembrane flip-flop diffusion in HBM systems, which involves the bending of the alkyl tail of the proton carrier as the rate-determining step. Additional studies with an unbendable proton carrier further validate these mechanistic findings. PMID- 27276264 TI - Oligomerization of the Tetraspanin CD81 via the Flexibility of Its delta-Loop. AB - Tetraspanins are master organizers in the plasma membrane, forming tetraspanin enriched microdomains with one another and other surface molecules. Their rod shaped structure includes a large extracellular loop (LEL) that plays a pivotal role in tetraspanin network formation. We performed comparative atomistic and coarse-grain molecular-dynamics simulations of the LEL in isolation and full length CD81, and reproduced LEL flexibility patterns known from wet-lab experiments in which the LEL delta-loop region showed a pronounced flexibility. In a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine lipid bilayer and a plasma membrane environment, the conformational flexibility of the delta-loop initiates CD81-CD81 contacts for oligomerization. Furthermore, in the plasma membrane, CD81 ganglioside bridges arising from preformed glycolipid patches cross-link the complexes. The data suggest that exposing a flexible domain enables binding to interaction partners by circumventing the restriction of orientation and conformational freedom of membrane proteins. PMID- 27276265 TI - A pH-Mediated Topological Switch within the N-Terminal Domain of Human Caveolin 3. AB - Caveolins mediate the formation of caveolae, which are small omega-shaped membrane invaginations involved in a variety of cellular processes. There are three caveolin isoforms, the third of which (Cav3) is expressed in smooth and skeletal muscles. Mutations in Cav3 cause a variety of human muscular diseases. In this work, we characterize the secondary structure, dynamics, and topology of the monomeric form of the full-length lipidated protein. Cav3 consists of a series of membrane-embedded or surface-associated helical elements connected by extramembrane connecting loops or disordered domains. Our results also reveal that the N-terminal domain undergoes a large scale pH-mediated topological rearrangement between soluble and membrane-anchored forms. Considering that roughly one-third of pathogenic mutations in Cav3 influence charged residues located in this domain, we hypothesize that this transition is likely to be relevant to the molecular basis of Cav3-linked diseases. These results provide insight into the structure of Cav3 and set the stage for mechanistic investigations of the effects of pathogenic mutations. PMID- 27276266 TI - The Functional Activity of the Human Serotonin 5-HT1A Receptor Is Controlled by Lipid Bilayer Composition. AB - Although the properties of the cell plasma membrane lipid bilayer are broadly understood to affect integral membrane proteins, details of these interactions are poorly understood. This is particularly the case for the large family of G protein-coupled receptors (GPCRs). Here, we examine the lipid dependence of the human serotonin 5-HT1A receptor, a GPCR that is central to neuronal function. We incorporate the protein in synthetic bilayers of controlled composition together with a fluorescent reporting system that detects GPCR-catalyzed activation of G protein to measure receptor-catalyzed oligonucleotide exchange. Our results show that increased membrane order induced by sterols and sphingomyelin increases receptor-catalyzed oligonucleotide exchange. Increasing membrane elastic curvature stress also increases this exchange. These results reveal the broad dependence that the 5-HT1A receptor has on plasma membrane properties, demonstrating that membrane lipid composition is a biochemical control parameter and highlighting the possibility that compositional changes related to aging, diet, or disease could impact cell signaling functions. PMID- 27276267 TI - Statistical Thermodynamics for Actin-Myosin Binding: The Crucial Importance of Hydration Effects. AB - Actomyosin is an important molecular motor, and the binding of actin and myosin is an essential research target in biophysics. Nevertheless, the physical factors driving or opposing the binding are still unclear. Here, we investigate the role of water in actin-myosin binding using the most reliable statistical-mechanical method currently available for assessing biomolecules immersed in water. This method is characterized as follows: water is treated not as a dielectric continuum but as an ensemble of molecules; the polyatomic structures of proteins are taken into consideration; and the binding free energy is decomposed into physically insightful entropic and energetic components by accounting for the hydration effect to its full extent. We find that the actin-myosin binding brings large gains of electrostatic and Lennard-Jones attractive interactions. However, these gains are accompanied by even larger losses of actin-water and myosin-water electrostatic and LJ attractive interactions. Although roughly half of the energy increase due to the losses is cancelled out by the energy decrease arising from structural reorganization of the water released upon binding, the remaining energy increase is still larger than the energy decrease brought by the gains mentioned above. Hence, the net change in system energy is positive, which opposes binding. Importantly, the binding is driven by a large gain of configurational entropy of water, which surpasses the positive change in system energy and the conformational entropy loss occurring for actin and myosin. The principal physical origin of the large water-entropy gain is as follows: the actin-myosin interface is closely packed with the achievement of high shape complementarity on the atomic level, leading to a large increase in the total volume available to the translational displacement of water molecules in the system and a resultant reduction of water crowding (i.e., entropic correlations among water molecules). PMID- 27276268 TI - Graphene Symmetry Amplified by Designed Peptide Self-Assembly. AB - We present a strategy for designed self-assembly of peptides into two-dimensional monolayer crystals on the surface of graphene and graphite. As predicted by computation, designed peptides assemble on the surface of graphene to form very long, parallel, in-register beta-sheets, which we call beta-tapes. Peptides extend perpendicularly to the long axis of each beta-tape, defining its width, with hydrogen bonds running along the axis. Tapes align on the surface to create highly regular microdomains containing 4-nm pitch striations. Moreover, in agreement with calculations, the atomic structure of the underlying graphene dictates the arrangement of the beta-tapes, as they orient along one of six directions defined by graphene's sixfold symmetry. A cationic-assembled peptide surface is shown here to strongly adhere to DNA, preferentially orienting the double helix along beta-tape axes. This orientational preference is well anticipated from calculations, given the underlying peptide layer structure. These studies illustrate how designed peptides can amplify the Angstrom-level atomic symmetry of a surface onto the micrometer scale, further imparting long range directional order onto the next level of assembly. The remarkably stable nature of these assemblies under various environmental conditions suggests applications in enzymelike catalysis, biological interfaces for cellular recognition, and two-dimensional platforms for studying DNA-peptide interactions. PMID- 27276269 TI - Competition between Coiled-Coil Structures and the Impact on Myosin-10 Bundle Selection. AB - Coiled-coil fusions are a useful approach to enforce dimerization in protein engineering. However, the final structures of coiled-coil fusion proteins have received relatively little attention. Here, we determine the structural outcome of adjacent parallel and antiparallel coiled coils. The targets are coiled coils that stabilize myosin-10 in single-molecule biophysical studies. We reveal the solution structure of a short, antiparallel, myosin-10 coiled-coil fused to the parallel GCN4-p1 coiled coil. Surprisingly, this structure is a continuous, antiparallel coiled coil where GCN4-p1 pairs with myosin-10 rather than itself. We also show that longer myosin-10 segments in these parallel/antiparallel fusions are dynamic and do not fold cooperatively. Our data resolve conflicting results on myosin-10 selection of actin filament bundles, demonstrating the importance of understanding coiled-coil orientation and stability. PMID- 27276270 TI - Actomyosin Cortical Mechanical Properties in Nonadherent Cells Determined by Atomic Force Microscopy. AB - The organization of filamentous actin and myosin II molecular motor contractility is known to modify the mechanical properties of the cell cortical actomyosin cytoskeleton. Here we describe a novel method, to our knowledge, for using force spectroscopy approach curves with tipless cantilevers to determine the actomyosin cortical tension, elastic modulus, and intracellular pressure of nonadherent cells. We validated the method by measuring the surface tension of water in oil microdrops deposited on a glass surface. We extracted an average tension of T ~ 20.25 nN/MUm, which agrees with macroscopic experimental methods. We then measured cortical mechanical properties in nonadherent human foreskin fibroblasts and THP-1 human monocytes before and after pharmacological perturbations of actomyosin activity. Our results show that myosin II activity and actin polymerization increase cortex tension and intracellular pressure, whereas branched actin networks decreased them. Interestingly, myosin II activity stiffens the cortex and branched actin networks soften it, but actin polymerization has no effect on cortex stiffness. Our method is capable of detecting changes in cell mechanical properties in response to perturbations of the cytoskeleton, allowing characterization with physically relevant parameters. Altogether, this simple method should be of broad application for deciphering the molecular regulation of cell cortical mechanical properties. PMID- 27276273 TI - Correction: Neuronal Cell Fate Specification by the Convergence of Different Spatiotemporal Cues on a Common Terminal Selector Cascade. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002450.]. PMID- 27276271 TI - A Computational Model of YAP/TAZ Mechanosensing. AB - In cell proliferation, stem cell differentiation, chemoresistance, and tissue organization, the ubiquitous role of YAP/TAZ continues to impact our fundamental understanding in numerous physiological and disease systems. YAP/TAZ is an important signaling nexus integrating diverse mechanical and biochemical signals, such as ECM stiffness, adhesion ligand density, or cell-cell contacts, and thus strongly influences cell fate. Recent studies show that YAP/TAZ mechanical sensing is dependent on RhoA-regulated stress fibers. However, current understanding of YAP/TAZ remains limited due to the unknown interaction between the canonical Hippo pathway and cell tension. Furthermore, the multiscale relationship connecting adhesion signaling to YAP/TAZ activity through cytoskeleton dynamics remains poorly understood. To identify the roles of key signaling molecules in mechanical signal sensing and transduction, we present a, to our knowledge, novel computational model of the YAP/TAZ signaling pathway. This model converts extracellular-matrix mechanical properties to biochemical signals via adhesion, and integrates intracellular signaling cascades associated with cytoskeleton dynamics. We perform perturbations of molecular levels and sensitivity analyses to predict how various signaling molecules affect YAP/TAZ activity. Adhesion molecules, such as FAK, are predicted to rescue YAP/TAZ activity in soft environments via the RhoA pathway. We also found that changes of molecule concentrations result in different patterns of YAP/TAZ stiffness response. We also investigate the sensitivity of YAP/TAZ activity to ECM stiffness, and compare with that of SRF/MAL, which is another important regulator of differentiation. In addition, the model shows that the unresolved synergistic effect of YAP/TAZ activity between the mechanosensing and the Hippo pathways can be explained by the interaction of LIM-kinase and LATS. Overall, our model provides a, to our knowledge, novel platform for studying YAP/TAZ activity in the context of integrating different signaling pathways. This platform can be used to gain, to our knowledge, new fundamental insights into roles of key molecular and mechanical regulators on development, tissue engineering, or tumor progression. PMID- 27276272 TI - Chloride Anions Regulate Kinetics but Not Voltage-Sensor Qmax of the Solute Carrier SLC26a5. AB - In general, SLC26 solute carriers serve to transport a variety of anions across biological membranes. However, prestin (SLC26a5) has evolved, now serving as a motor protein in outer hair cells (OHCs) of the mammalian inner ear and is required for cochlear amplification, a mechanical feedback mechanism to boost auditory performance. The mechanical activity of the OHC imparted by prestin is driven by voltage and controlled by anions, chiefly intracellular chloride. Current opinion is that chloride anions control the Boltzmann characteristics of the voltage sensor responsible for prestin activity, including Qmax, the total sensor charge moved within the membrane, and Vh, a measure of prestin's operating voltage range. Here, we show that standard narrow-band, high-frequency admittance measures of nonlinear capacitance (NLC), an alternate representation of the sensor's charge-voltage (Q-V) relationship, is inadequate for assessment of Qmax, an estimate of the sum of unitary charges contributed by all voltage sensors within the membrane. Prestin's slow transition rates and chloride-binding kinetics adversely influence these estimates, contributing to the prevalent concept that intracellular chloride level controls the quantity of sensor charge moved. By monitoring charge movement across frequency, using measures of multifrequency admittance, expanded displacement current integration, and OHC electromotility, we find that chloride influences prestin kinetics, thereby controlling charge magnitude at any particular frequency of interrogation. Importantly, however, this chloride dependence vanishes as frequency decreases, with Qmax asymptoting at a level irrespective of the chloride level. These data indicate that prestin activity is significantly low-pass in the frequency domain, with important implications for cochlear amplification. We also note that the occurrence of voltage-dependent charge movements in other SLC26 family members may be hidden by inadequate interrogation timescales, and that revelation of such activity could highlight an evolutionary means for kinetic modifications within the family to address hearing requirements in mammals. PMID- 27276274 TI - Alcohol-Tolerant Platinum Electrocatalyst for Oxygen Reduction by Encapsulating Platinum Nanoparticles inside Nitrogen-Doped Carbon Nanocages. AB - Pt-based electrocatalysts are the most popular for direct alcohol fuel cells, but their performances easily deteriorate for the oxygen reduction reaction (ORR) at the cathode because of the alcohol crossover effect. Herein, we report the novel Pt electrocatalyst encapsulated inside nitrogen-doped carbon nanocages (Pt@NCNC), which presents excellent alcohol-tolerant ORR activity and durability in acidic media, far superior to the Pt counterpart immobilized outside the nanocages (Pt/NCNC). The superb performance is correlated with the molecule-sieving effect of the micropores penetrating through the shells of the nanocages, which admit the small-sized oxygen and ions but block the large-sized alcohols into the nanocages. This mechanism is confirmed by examining the size dependence of ORR and alcohol oxidation activities by regulating the micropores sizes. This study provides a promising strategy to develop the superior alcohol-tolerant Pt-based ORR electrocatalyst in acidic media. PMID- 27276276 TI - Nonparametric analysis of competing risks data with event category missing at random. AB - In competing risks setup, the data for each subject consist of the event time, censoring indicator, and event category. However, sometimes the information about the event category can be missing, as, for example, in a case when the date of death is known but the cause of death is not available. In such situations, treating subjects with missing event category as censored leads to the underestimation of the hazard functions. We suggest nonparametric estimators for the cumulative cause-specific hazards and the cumulative incidence functions which use the Nadaraya-Watson estimator to obtain the contribution of an event with missing category to each of the cause-specific hazards. We derive the propertied of the proposed estimators. Optimal bandwidth is determined, which minimizes the mean integrated squared errors of the proposed estimators over time. The methodology is illustrated using data on lung infections in patients from the United States Cystic Fibrosis Foundation Patient Registry. PMID- 27276275 TI - Posttraumatic stress disorder symptoms in youth with vs without chronic pain. AB - Chronic pain and posttraumatic stress disorder (PTSD) symptoms have been found to co-occur in adults; however, research has not examined this co-occurrence in adolescence, when pediatric chronic pain often first emerges. The aims of this study were to compare the frequency and intensity of PTSD symptoms and stressful life events in cohorts of youth with (n = 95) and without (n = 100) chronic pain and their parents and to determine the association between PTSD symptoms, health related quality of life, and pain symptoms within the chronic pain sample. All participants completed questionnaire measures through an online survey. Findings revealed that youth with chronic pain and their parents had significantly higher levels of PTSD symptoms as compared with pain-free peers. More youth with chronic pain (32%) and their parents (20%) reported clinically significant elevations in PTSD symptoms than youth without chronic pain (8%) and their parents (1%). Youth with chronic pain also reported a greater number of stressful life events than those without chronic pain, and this was associated with higher PTSD symptoms. Among the chronic pain cohort, higher levels of PTSD symptoms were predictive of worse health-related quality of life and were associated with higher pain intensity, unpleasantness, and interference. Results suggest that elevated PTSD symptoms are common and linked to reduced functioning among youth with chronic pain. Future research is needed to examine PTSD at the diagnostic level and the underlying mechanisms that may explain why this co-occurrence exists. PMID- 27276277 TI - An effective host material with thermally activated delayed fluorescence formed by confined conjugation for red phosphorescent organic light-emitting diodes. AB - A thermally activated delayed fluorescence material 2,6-bis(9,9-diphenylacridin 10(9H)-yl)pyrazine was designed and synthesized. The twisted configuration made it possesses very small singlet-triplet splitting. A red electroluminescent device based on this new host material is able to achieve ~26% external quantum efficiency and relatively flat efficiency roll-off. PMID- 27276278 TI - Application of electrochemical impedance spectroscopy: A phase behavior study of babassu biodiesel-based microemulsions. AB - Microemulsions are thermodynamically stable systems of two immiscible liquids, one aqueous and the other of organic nature, with a surfactant and/or co surfactant adsorbed in the interface between the two phases. Biodiesel-based microemulsions, consisting of alkyl esters of fatty acids, open a new means of analysis for the application of electroanalytical techniques, and is advantageous as it eliminates the required pre-treatment of a sample. In this work, the phase behaviours of biodiesel-based microemulsions were investigated through the electrochemical impedance spectroscopy (EIS) technique. We observed thatan increase in the amount of biodiesel in the microemulsion formulation increases the resistance to charge transfer at the interface. Also, the electrical conductivity measurements revealed that a decrease or increase in electrical properties depends on the amount of biodiesel. EIS studies of the biodiesel-based microemulsion samples showed the presence of two capacitive arcs: one high frequency and the other low-frequency. Thus, the formulation of microemulsions plays an important role in estimating the electrical properties through the electrochemical impedance spectroscopy technique. PMID- 27276279 TI - Origin of the Order-Disorder Transition and the Associated Anomalous Change of Thermopower in AgBiS2 Nanocrystals: A Combined Experimental and Theoretical Study. AB - Bulk AgBiS2 crystallizes in a trigonal crystal structure (space group, P3m1) at room temperature, which transforms to a cation disordered rock salt structure (space group, Fm3m) at ~473 K. Surprisingly, at room temperature, a solution grown nanocrystal of AgBiS2 crystallizes in a metastable Ag/Bi ordered cubic structure, which transforms to a thermodynamically stable disorded cubic structure at 610 K. Moreover, the order-disorder transition in nanocrystalline AgBiS2 is associated with an unusual change in thermopower. Here, we shed light on the origin of a order-disorder phase transition and the associated anomalous change of thermopower in AgBiS2 nanocrystals by using a combined experimental, density functional theory based first-principles calculation and ab initio molecular dynamics simulations. Positron-annilation spectroscopy indicates the presence of higher numbers of Ag vacancies in the nanocrystal compared to that of the bulk cubic counterpart at room temperature. Furthermore, temperature dependent two-detector coincidence Doppler broadening spectroscopy and Doppler broadening of the annihilation radiation (S parameter) indicate that the Ag vacancy concentration increases abruptly during the order-disorder transition in nanocrystalline AgBiS2. At high temperature, a Ag atom shuttles between the vacancy and interstitial sites to form a locally disordered cation sublattice in the nanocrystal, which is facilitated by the formation of more Ag vacancies during the phase transition. This process increases the entropy of the system at higher vacancy concentration, which, in turn, results in the unusual rise in thermopower. PMID- 27276337 TI - Low-Temperature Chemical Vapor Deposition Synthesis of Pt-Co Alloyed Nanoparticles with Enhanced Oxygen Reduction Reaction Catalysis. AB - Novel Pt-Co alloyed nanocatalysts are generated via chemical vapor deposition assisted facile one-pot synthesis. The method guarantees highly monodisperse Pt Co alloy nanoparticles with precise control of metallic compositions within 1 at%. A significant features is that a perfectly alloyed single-crystal structure is obtained at temperatures as low as 500 degrees C, which is much lower than conventional alloying temperatures. PMID- 27276338 TI - Yields and Time-of-Flight Spectra of Neutral High-Rydberg Fragments at the K Edges of the CO2 Molecule. AB - We have studied the production of neutral fragments in high-Rydberg (HR) states at the C 1s and O 1s edges of the CO2 molecule by performing two kinds of experiments. First, the yields of neutral HR fragments were measured indirectly by ionizing such fragments in a static electric field and by collecting resulting singly charged positive ions as a function of the photon energy. Such measurements reveal not only excitations below the core ionization thresholds but also thresholds for single core-hole and shakeup photoionization. Second, we obtained the mass spectra of neutral HR fragments at selected photon energies by exploiting pulsed field ionization; they show atomic fragments C(HR) and O(HR). We discuss dissociation pathways leading to the production of neutral HR fragments in core excitation and ionization of CO2. PMID- 27276339 TI - Electrospun Gelatin Fibers with a Multiple Release of Antibiotics Accelerate Dermal Regeneration in Infected Deep Burns. AB - Electrospun fibers of hydrophilic polymers meet challenges in a rapid degradation of fiber matrices and discharge of antibiotics to comply with requirements of infection control as a dermal regeneration template. In the current study, a pH conversion process is initially developed to ensure fluent electrospinning, an efficient in situ cross-linking of electrospun gelatin fibers with oxidized alginate and simultaneous loading of gentamicin sulfate (GS) and hydrophobic ciprofloxacin into fibers. The dual drug-loaded fibers indicate a complete release of GS during 6 d and a sustained release of ciprofloxacin for over three weeks, and the antibiotics release indicates significant growth inhibitions on Pseudomonas aeruginosa and Staphylococcus epidermidis. The wound healing efficacy is evaluated on a deep burn model infected with 10(8) CFU of P. aeruginosa. Compared with fibers with loaded individual drugs, the concomitant release of GS and ciprofloxacin significantly reduces the bacteria numbers in wound and livers, at around 2.30 * 10(5) and 1.25 * 10(3) CFU after 3 d, respectively. The wound re epithelization, blood vessel formation, collagen deposition, and tissue remodeling process are accelerated with a complete healing observed after 21 d. This study provides a feasible strategy to design cross-linked hydrophilic fibers with an extended drug release for biomedical applications. PMID- 27276340 TI - The sensory-motor profile awake-A new tool for pre-, intra-, and postoperative assessment of sensory-motor function. AB - OBJECTIVES: Awake craniotomy is a well-established procedure in surgery of intracranial tumors in eloquent areas. However, sufficiently standardized instruments for the assessment of sensory-motor function before, during and after the operation are currently lacking, despite their importance for evaluation of operative outcome. PATIENTS AND METHODS: To address this issue, we designed a standardized assessment tool (the "sensory-motor profile awake scale"; SMP-a). The final scale consists of three motor sections (face, arm and leg) assessing both gross and fine motor skills and one sensory section. It differentiates between six grades of impairment and its tasks are applicable for intraoperative continuous monitoring of sensory-motor functions and supporting processes. We analyzed the data of 17 patients with intracranial tumors eligible for awake craniotomy who were preoperatively assessed with the SMP-a. In addition, we present an exemplary case. RESULTS: Our data support the assumption that the SMP a is feasible in patients eligible for awake craniotomy, even in patients with symptoms of mild aphasia or more severe sensory-motor deficits caused by tumor recurrence. The exemplary case demonstrates the feasibility of repeated measures with the SMP-a in a tumor patient, including the adaption of tasks to the individual requirements of an intraoperative setting. CONCLUSION: This exploratory study suggests that the SMP-a might be a feasible rating scale in patients with intracranial tumors. The flexibility of the scale enables individual adaption, but preserves the standardized scoring system to allow comparison between assessment dates, patients and, hopefully in the future, institutions. However, future studies are mandatory to provide data on the instrument's diagnostic properties with respect to feasibility, objectivity, validity and reliability. PMID- 27276341 TI - Dynamic Contact Angle at the Nanoscale: A Unified View. AB - Generation of a dynamic contact angle in the course of wetting is a fundamental phenomenon of nature. Dynamic wetting processes have a direct impact on flows at the nanoscale, and therefore, understanding them is exceptionally important to emerging technologies. Here, we reveal the microscopic mechanism of dynamic contact angle generation. It has been demonstrated using large-scale molecular dynamics simulations of bead-spring model fluids that the main cause of local contact angle variations is the distribution of microscopic force acting at the contact line region. We were able to retrieve this elusive force with high accuracy. It has been directly established that the force distribution can be solely predicted on the basis of a general friction law for liquid flow at solid surfaces by Thompson and Troian. The relationship with the friction law provides both an explanation of the phenomenon of dynamic contact angle and a methodology for future predictions. The mechanism is intrinsically microscopic, universal, and irreducible and is applicable to a wide range of problems associated with wetting phenomena. PMID- 27276342 TI - Catalytic C(sp(3) )-H Arylation of Free Primary Amines with an exo Directing Group Generated In Situ. AB - Herein, we report the palladium-catalyzed direct arylation of unactivated aliphatic C-H bonds in free primary amines. This method takes advantage of an exo imine-type directing group (DG) that can be generated and removed in situ. A range of unprotected aliphatic amines are suitable substrates, undergoing site selective arylation at the gamma-position. Methyl as well as cyclic and acyclic methylene groups can be activated. Furthermore, when aniline-derived substrates were used, preliminary success with delta-C-H arylation was achieved. The feasibility of using the DG component in a catalytic fashion was also demonstrated. PMID- 27276343 TI - Validity of Different Delirium Assessment Tools for Critically Ill Children: Covariates Matter. AB - OBJECTIVES: To evaluate test validity of the Pediatric Confusion Assessment Method for the ICU, the Pediatric Anesthesia Emergence Delirium scale, and the newly developed severity scale for the Pediatric Confusion Assessment Method for the ICU; to prospectively assess covariates and their influence on test validity of the scores. DESIGN: Prospective observational cohort study. SETTING: PICU of a tertiary care medical center. PATIENTS: Critically ill patients 5 years old or older ventilated or nonventilated with an ICU length of stay of at least 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were scored with the Pediatric Confusion Assessment Method for the ICU and the Pediatric Anesthesia Emergence Delirium scale once daily for a maximum of 21 days. Validity was determined by comparing scoring results with the evaluations of the delirium experts who used the criteria of the Diagnostic and Statistical Manual, 4th Edition, Text Revision, for delirium diagnosis. Sixty-four patients were enrolled and 214 assessments were conducted and included in data analysis. The first assessments within each patient revealed sensitivities of 69.2% for the Pediatric Anesthesia Emergence Delirium scale, 76.9% for the Pediatric Confusion Assessment Method for the ICU, and 84.9% for the severity scale for the Pediatric Confusion Assessment Method for the ICU. Specificities were 98% for all scores. Considering repeated measurements, sensitivities decreased to 35.9% for the Pediatric Anesthesia Emergence Delirium scale and to 52.3% for the Pediatric Confusion Assessment Method for the ICU. The sensitivity of the severity scale for the Pediatric Confusion Assessment Method for the ICU dropped to 71.8%, which was significantly higher compared to the Pediatric Anesthesia Emergence Delirium scale (p = 0.0008). Receiver operator characteristic regression unveiled that sedation and mechanical ventilation had a significant negative effect on the validity of the Pediatric Anesthesia Emergence Delirium scale and the severity scale for the Pediatric Confusion Assessment Method for the ICU. Age and gender had a significant impact on the receiver operator characteristic curve of the severity scale for the Pediatric Confusion Assessment Method for the ICU. CONCLUSIONS: The severity scale for the Pediatric Confusion Assessment Method for the ICU showed the best test validity when used in critically ill children of 5 years old or older. Nevertheless, validity of delirium screening itself depends on patient specific factors. These factors should be taken into consideration when choosing a delirium screening instrument. PMID- 27276345 TI - A Glimpse of Our Journey into the Design of Optical Probes in Self-assembled Surfactant Aggregates. AB - Dynamic self-assembling amphiphilic surfactant molecules, popularly known as "micelles", have received widespread attention, due to their ability to modulate the photophysical properties of various organic dyes upon encapsulation. Along with their well-known use as cleaning agents, catalysts in organic reactions, and even for drug delivery purposes, these surfactant assemblies also show promising pertinence in the recognition of both ionic and nonionic targeted analytes. Low micropolarity and relatively hydrophobic environments promote their interaction with ionic analytes, whereas neutral species mostly affect the aggregation pattern of the probe molecules upon partitioning inside the micellar hydrophobic milieu. The environment-sensitive nature of micelle-based self-assembled probes also prompts us to devise new sensor arrays for the recognition of multiple analytes. While this account will largely focus on our own work in developing surfactant-triggered self-assembled sensors, our findings have been placed in the context of the relevant contributions from others during their strategic evolution. PMID- 27276344 TI - Relationship Between African-American Race and Delirium in the ICU. AB - OBJECTIVES: Delirium is a highly prevalent syndrome of acute brain dysfunction among critically ill patients that has been linked to multiple risk factors, such as age, preexisting cognitive impairment, and use of sedatives; but to date, the relationship between race and delirium is unclear. We conducted this study to identify whether African-American race is a risk factor for developing ICU delirium. DESIGN: A prospective cohort study. SETTING: Medical and surgical ICUs of a university-affiliated, safety net hospital in Indianapolis, IN. PATIENTS: A total of 2,087 consecutive admissions with 1,008 African Americans admitted to the ICU services from May 2009 to August 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Incident delirium was defined as first positive Confusion Assessment Method for the ICU result after an initial negative Confusion Assessment Method for the ICU; and prevalent delirium was defined as positive Confusion Assessment Method for the ICU on first Confusion Assessment Method for the ICU assessment. The overall incident delirium rate in African Americans was 8.7% compared with 10.4% in Caucasians (p = 0.26). The prevalent delirium rate was 14% in both African Americans and Caucasians (p = 0.95). Significant age and race interactions were detected for incident delirium (p = 0.02) but not for prevalent delirium (p = 0.3). The hazard ratio for incident delirium for African Americans in the 18-49 years age group compared with Caucasians of similar age was 0.4 (0.1-0.9). The hazard and odds ratios for incident and prevalent delirium in other groups were not different. CONCLUSIONS: African-American race does not confer any additional risk for developing incident or prevalent delirium in the ICU. Instead, younger African Americans tend to have lower rates of incident delirium compared with Caucasians of similar age. PMID- 27276346 TI - Interleukin-31 Polymorphisms and Serum IL-31 Level in Patients with Mastocytosis: Correlation with Clinical Presen-tation and Pruritus. AB - Data on interleukin-31 (IL-31) involvement in the patho-genesis of mastocytosis, and its impact on pruritus development in the disease, are limited. The aim of this study was to analyse distinct IL-31 gene polymorphisms in 127 patients (age 0.5-76 years) with mastocytosis and their correlation with clinical presentation, pruritus and serum IL-31 levels. In patients with mastocytosis, the frequency of IL-31 IVS2+12AA genotype and IVS2+12A allele was higher than in control subjects and they were linked to an increased risk of development of mastocytosis. In adult patients, but not in children, -2057AA genotype was also associated with an increased risk of occurrence of mastocytosis. Pruritus affected 83.3% of 78 adult patients with mastocytosis, and a positive correlation between serum IL-31 levels and pruritus was found in these patients. In conclusion, distinct polymorphic variants of the IL-31 gene may be involved in the patho-genesis of mastocytosis, and IL-31 may be involved in the induction of pruritus in patients with mastocytosis. PMID- 27276350 TI - Historical Identification of Melanoma-Dark, Deep, and Deadly. PMID- 27276351 TI - Sugaring-Modern Revival of an Ancient Egyptian Technique for Hair Removal. PMID- 27276352 TI - Purity in the Eye of the Beholder-Home Remedies for Freckles. PMID- 27276347 TI - Characterising the Canine Oral Microbiome by Direct Sequencing of Reverse Transcribed rRNA Molecules. AB - PCR amplification and sequencing of phylogenetic markers, primarily Small Sub Unit ribosomal RNA (SSU rRNA) genes, has been the paradigm for defining the taxonomic composition of microbiomes. However, 'universal' SSU rRNA gene PCR primer sets are likely to miss much of the diversity therein. We sequenced a library comprising purified and reverse-transcribed SSU rRNA (RT-SSU rRNA) molecules from the canine oral microbiome and compared it to a general bacterial 16S rRNA gene PCR amplicon library generated from the same biological sample. In addition, we have developed BIONmeta, a novel, open-source, computer package for the processing and taxonomic classification of the randomly fragmented RT-SSU rRNA reads produced. Direct RT-SSU rRNA sequencing revealed that 16S rRNA molecules belonging to the bacterial phyla Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria and Spirochaetes, were most abundant in the canine oral microbiome (92.5% of total bacterial SSU rRNA). The direct rRNA sequencing approach detected greater taxonomic diversity (1 additional phylum, 2 classes, 1 order, 10 families and 61 genera) when compared with general bacterial 16S rRNA amplicons from the same sample, simultaneously provided SSU rRNA gene inventories of Bacteria, Archaea and Eukarya, and detected significant numbers of sequences not recognised by 'universal' primer sets. Proteobacteria and Spirochaetes were found to be under-represented by PCR-based analysis of the microbiome, and this was due to primer mismatches and taxon-specific variations in amplification efficiency, validated by qPCR analysis of 16S rRNA amplicons from a mock community. This demonstrated the veracity of direct RT-SSU rRNA sequencing for molecular microbial ecology. PMID- 27276353 TI - Dermatology and Comic Book Characters. PMID- 27276354 TI - Exfoliative Excrement. PMID- 27276355 TI - Cryotherapy-As Ancient as the Pharaohs. PMID- 27276356 TI - Hidradenitis Suppurativa. PMID- 27276358 TI - Weighing the evidence for weight loss as a therapeutic strategy for atrial fibrillation. PMID- 27276359 TI - Ammonium hydroxide modulated synthesis of high-quality fluorescent carbon dots for white LEDs with excellent color rendering properties. AB - A novel type of aqueous fluorescent carbon dot (CD) was synthesized using citric acid as the only carbon source via an ammonium hydroxide modulated method, providing a blue color gamut. The amino group is considered to be the key factor in the high fluorescence of CDs and a model is established to investigate the mechanism of fluorescence. In addition, white light-emitting diodes (WLEDs) are fabricated by utilizing the prepared CDs and rare earth luminescent materials (SrSi2O2N2:Eu and Sr2Si5N8:Eu) as color conversion layers and UV-LED chips as the excitation light source. The WLEDs produce bright white light with attractive color rendering properties including a color rendering index of up to 95.1, a CIE coordinate of (0.33, 0.37), and a T c of 5447 K under a 100 mA driven current, indicating that the CDs are promising in the field of optoelectronic devices. PMID- 27276357 TI - (11)C[double bond, length as m-dash]O bonds made easily for positron emission tomography radiopharmaceuticals. AB - The positron-emitting radionuclide carbon-11 ((11)C, t1/2 = 20.3 min) possesses the unique potential for radiolabeling of any biological, naturally occurring, or synthetic organic molecule for in vivo positron emission tomography (PET) imaging. Carbon-11 is most often incorporated into small molecules by methylation of alcohol, thiol, amine or carboxylic acid precursors using [(11)C]methyl iodide or [(11)C]methyl triflate (generated from [(11)C]carbon dioxide or [(11)C]methane). Consequently, small molecules that lack an easily substituted (11)C-methyl group are often considered to have non-obvious strategies for radiolabeling and require a more customized approach. [(11)C]Carbon dioxide itself, [(11)C]carbon monoxide, [(11)C]cyanide, and [(11)C]phosgene represent alternative reactants to enable (11)C-carbonylation. Methodologies developed for preparation of (11)C-carbonyl groups have had a tremendous impact on the development of novel PET tracers and provided key tools for clinical research. (11)C-Carbonyl radiopharmaceuticals based on labeled carboxylic acids, amides, carbamates and ureas now account for a substantial number of important imaging agents that have seen translation to higher species and clinical research of previously inaccessible targets, which is a testament to the creativity, utility and practicality of the underlying radiochemistry. PMID- 27276360 TI - Short-term toxicity studies of loline alkaloids in mice. AB - Epichloe endophytes have been used successfully in pastoral systems to reduce the impact of insect pests through the expression of secondary metabolites. The use of endophytes could be extended to other plant species, such as cereal crops, where the production of bioactive secondary metabolites would reduce the reliance on pesticides for insect control. The success of this approach is dependent on the selection of an appropriate secondary metabolite target which must not only be effective against insect pests but also be safe for grazing and monogastric animals. The loline alkaloids have been identified as possible target metabolites as they are associated with potent effects on insects and low toxicity to grazing animals. The purpose of the current study was to generate toxicological data on the loline alkaloids in a monogastric system using mice. Male and female mice were fed 415 mg/kg/day total lolines for a 3-week period. The loline treatment caused no statistically significant effect on gross pathology, histology, haematology, blood chemistry, heart rate, blood pressure or motor coordination. Reduced weight gain and food consumption were noted in the loline groups during the initial stages of the experiment. This experiment raises no food safety concerns for the loline alkaloids. PMID- 27276361 TI - WHO strategies for the programmatic management of drug-resistant tuberculosis. AB - INTRODUCTION: Adequate management of drug-resistant tuberculosis (TB), including multidrug- (MDR) and extensively drug-resistant (XDR-) TB are within the priorities of the newly launched World Health Organization's End TB and Elimination Strategies. AREAS COVERED: This manuscript presents the evidence on the MDR- /XDR-TB epidemiology and discusses how the five recommended priority actions can be applied at the programmatic level to tackle the epidemic: 1) prevent development of MDR-TB thorough high quality treatment of drug- susceptible TB; 2) expand rapid testing and detection of drug-resistant TB; 3) provide immediate access to effective treatment and proper care; 4) prevent transmission through infection control; 5) increase political commitment and financing. A non-systematic review using Pubmed was carried out in addition to additional relevant information taken from the abstracts of international scientific conferences. Expert commentary: Current and future control of MDR-TB significantly relies on the correct use of new diagnostics and new drugs from one side, and on the consistent application of the five core interventions at the programmatic level. In addition, it is mandatory to tackle the social determinants and socio-economic barriers favouring the MDR-TB, otherwise it will not be possible to reach the planned goals as well as TB Elimination. PMID- 27276362 TI - The Effect of Reduced Water Availability in the Great Ruaha River on the Vulnerable Common Hippopotamus in the Ruaha National Park, Tanzania. AB - In semi-arid environments, 'permanent' rivers are essential sources of surface water for wildlife during 'dry' seasons when rainfall is limited or absent, particularly for species whose resilience to water scarcity is low. The hippopotamus (Hippopotamus amphibius) requires submersion in water to aid thermoregulation and prevent skin damage by solar radiation; the largest threat to its viability are human alterations of aquatic habitats. In the Ruaha National Park (NP), Tanzania, the Great Ruaha River (GRR) is the main source of surface water for wildlife during the dry season. Recent, large-scale water extraction from the GRR by people upstream of Ruaha NP is thought to be responsible for a profound decrease in dry season water-flow and the absence of surface water along large sections of the river inside the NP. We investigated the impact of decreased water flow on daytime hippo distribution using regular censuses at monitoring locations, transects and camera trap records along a 104km section of the GRR within the Ruaha NP during two dry seasons. The minimum number of hippos per monitoring location increased with the expanse of surface water as the dry seasons progressed, and was not affected by water quality. Hippo distribution significantly changed throughout the dry season, leading to the accumulation of large numbers in very few locations. If surface water loss from the GRR continues to increase in future years, this will have serious implications for the hippo population and other water dependent species in Ruaha NP. PMID- 27276363 TI - Analysis of the genetic diversity of Candida isolates obtained from diabetic patients and kidney transplant recipients. AB - Yeasts of the genus Candida have high genetic variability and are the most common opportunistic pathogenic fungi in humans. In this study, we evaluated the genetic diversity among 120 isolates of Candida spp. obtained from diabetic patients, kidney transplant recipients and patients without any immune deficiencies from Parana state, Brazil. The analysis was performed using the ITS1-5.8S-ITS2 region and a partial sequence of 28S rDNA. In the phylogenetic analysis, we observed a consistent separation of the species C. albicans, C. dubliniensis, C. glabrata, C. tropicalis, C. parapsilosis, C. metapsilosis and C. orthopsilosis, however with low intraspecific variability. In the analysis of the C. albicans species, two clades were formed. Clade A included the largest number of isolates (91.2%) and the majority of isolates from GenBank (71.4%). The phylogenetic analysis showed low intraspecific genetic diversity, and the genetic polymorphisms between C. albicans isolates were similar to genetic divergence found in other studies performed with isolates from Brazil. This low genetic diversity of isolates can be explained by the geographic proximity of the patients evaluated. It was observed that yeast colonisation was highest in renal transplant recipients and diabetic patients and that C. albicans was the species most frequently isolated. PMID- 27276364 TI - Highly active ozonides selected against drug resistant malaria. AB - Ever increasing multi-drug resistance by Plasmodium falciparum is creating new challenges in malaria chemotherapy. In the absence of licensed vaccines, treatment and prevention of malaria is heavily dependent on drugs. Potency, range of activity, safety, low cost and ease of administration are crucial issues in the design and formulation of antimalarials. We have tested three synthetic ozonides NAC89, LC50 and LCD67 in vitro and in vivo against multidrug resistant Plasmodium. In vitro, LC50 was at least 10 times more efficient inhibiting P. falciparum multidrug resistant Dd2 strain than chloroquine and mefloquine and as efficient as artemisinin (ART), artesunate and dihydroartemisinin. All three ozonides showed high efficacy in clearing parasitaemia in mice, caused by multi drug resistant Plasmodium chabaudi strains, by subcutaneous administration, demonstrating high efficacy in vivo against ART and artesunate resistant parasites. PMID- 27276365 TI - Doxazosin, an alpha-1-adrenergic-receptor Antagonist, for Nightmares in Patients with Posttraumatic Stress Disorder and/or Borderline Personality Disorder: a Chart Review. AB - Objective: Centrally active alpha-1-adrenergic-receptor antagonists such as prazosin are effective in the treatment of nightmares in patients with posttraumatic stress disorder (PTSD). A pharmacological alternative is doxazosin, which has a longer half-life and fewer side effects. However, doxazosin is currently being used without solid empirical evidence. Furthermore, no study so far has assessed the effects of alpha-1-antagonists on nightmares in patients with borderline personality disorder (BPD). We retrospectively assessed the effectiveness of doxazosin on nightmares in PTSD and BPD. Method: A retrospective chart review of patients treated with doxazosin for trauma-associated nightmares in our clinic was performed. As in previous prazosin studies, the B2 score of the Clinician-Administered PTSD Scale (CAPS) was used as the primary outcome measure. Furthermore, the Pittsburgh Sleep Quality Index-Addendum for PTSD (PSQI-A) and sleep logs were analyzed. Results: We identified 51 patients with PTSD and/or BPD (mean age 35.7 years, 92.3% women) who received doxazosin for nightmares. Of these, 46 patients continued doxazosin over a 4-week period and 31 patients over a 12-week period. Within the 12-week period, doxazosin treatment significantly reduced nightmares regardless of PTSD/BPD. 25 percent of patients treated for 12 weeks had full remission of nightmares. PSQI-A scores indicated that additional trauma-associated sleep symptoms improved over 12 weeks. Furthermore, recuperation of sleep improved with doxazosin within the first 4 weeks of treatment. Conclusion: Doxazosin might improve trauma associated nightmares and more general sleep parameters in patients with PTSD and BPD. Randomized controlled trials are warranted. PMID- 27276366 TI - Translocator Protein (TSPO) Expression in Platelets of Depressed Patients Decreases during Antidepressant Therapy. AB - Introduction: A promising candidate in the field of pharmacological treatment options regarding major depressive disorder (MDD) is the mitochondrial translocator protein (18 kDa) (TSPO). TSPO is crucial for neurosteroid synthesis, which is in turn important for the regulation of emotions. It has already been shown that TSPO expression in platelets of depressed patients is reduced compared to healthy subjects. Methods: We measured TSPO levels in platelets of 37 depressed patients before and after 6 weeks of pharmacological treatment to test the hypotheses that i) such treatment would increase TSPO expression and ii) that this increase would be correlated with therapeutic response. Results: Surprisingly, TSPO levels in platelets of all patients were significantly reduced after 6 weeks of treatment (p=0.044). Within the responder group, a non significant trend towards greater TSPO level reduction could be observed. Discussion: These results challenge our hypotheses that TSPO levels might increase during antidepressant therapy along with a decrease in depressive symptoms. Thus, we assume that TSPO expression in platelets is not a suitable state marker for MDD. PMID- 27276367 TI - An Older Female Patient With Abdominal Distention. PMID- 27276369 TI - Short-segment and intrasphincteric gastroesophageal reflux. AB - PURPOSE OF REVIEW: The traditional gold standard for measuring gastroesophageal acid reflux has been by placing a pH sensor 5 cm proximal to the lower esophageal sphincter. It is known that damage induced by reflux is maximal near to the gastroesophageal junction and this has stimulated interest in determining acid reflux at that site. RECENT FINDINGS: The extent of esophageal exposure from refluxing gastric acid is inversely related to the distance proximal to the gastroesophageal junction. In addition, the pH transition point from gastric to esophageal pH can be displaced proximally within the lower esophageal sphincter without complete loss of sphincter tone. This intrasphincteric reflux is associated with proximal extension of cardia mucosa because of columnar metaplasia of the most distal esophageal squamous mucosa. SUMMARY: The most distal esophageal mucosa is exposed to substantially greater gastric acid refluxate than that recorded at the traditional site 5 cm proximal to the lower esophageal sphincter. PMID- 27276368 TI - Determination of risk for Barrett's esophagus and esophageal adenocarcinoma. AB - PURPOSE OF REVIEW: The incidence of esophageal adenocarcinoma and its precursor, Barrett's esophagus, have increased greatly over the past 40 years and continue to rise. This report summarizes the most recent data on the risk factors for Barrett's esophagus and esophageal adenocarcinoma. RECENT FINDINGS: Other factors, highly correlated with increasing trends for obesity, are the dominant driver of the increase in incidence of esophageal adenocarcinoma, interacting with gastroesophageal reflux disease symptoms. Abdominal obesity, independently of gastroesophageal reflux disease symptoms, is associated with increased risk of Barrett's esophagus and this association is likely mediated by high levels of leptin and insulin. Use of aspirin, nonsteroidal anti-inflammatory drugs, statins, and proton pump inhibitors are associated with a reduced risk of Barrett's esophagus as well as lower risk of neoplastic progression in patients with Barrett's esophagus. An increasing number of genetic loci have been associated with risk of Barrett's esophagus and esophageal adenocarcinoma. SUMMARY: Recent advances in identifying risk factors and reporting of more precise estimates of effect for the main risk factors will positively impact clinical risk stratification efforts for Barrett's esophagus and esophageal adenocarcinoma. Large pooling studies are underway to derive and validate reliable clinical risk models. PMID- 27276370 TI - Common variable immunodeficiency, immune thrombocytopenia, rituximab and splenectomy: important considerations. AB - Common variable immunodeficiency (CVID) is readily considered in patients presenting with recurrent sino-pulmonary infections, however this disease has a broad range of clinical manifestations and diagnosis can be delayed by several years. We present the case of a 44-year-old postpartum female who presented with nausea, vomiting and abdominal distension. Four years prior, she was hospitalized for treatment of immune thrombocytopenia (ITP) with splenectomy and rituximab followed by two episodes of bacterial meningitis despite immunizations. The recurrent meningitis had been attributed to splenectomy and immunotherapy. During this hospitalization, extensive workup for gastrointestinal pathology was negative and she was diagnosed with intestinal pseudo-obstruction. Her hospital course was complicated by development of severe pseudomonas pneumonia, and subsequent immunoglobulin testing and impaired antibody response to vaccines were consistent with CVID. We review the clinical presentation of CVID, its association with autoimmune disease, and treatment implications, specifically the impact of rituximab therapy and splenectomy on immunoglobulin function and risk of serious infection. Intestinal pseudo-obstruction has been reported in children with CVID, but literature search failed to reveal similar presentation in adults. Physicians must consider the heterogeneous clinical manifestations of CVID to avoid delay in diagnosis and treatment. Institution of appropriate therapy with immunoglobulin replacement is important to decrease risk of serious infection. PMID- 27276371 TI - A Perspective on the Trends and Challenges Facing Porphyrin-Based Anti-Microbial Materials. AB - The emergence of multidrug resistant bacterium threatens to unravel global healthcare systems, built up over centuries of medical research and development. Current antibiotics have little resistance against this onslaught as bacterium strains can quickly evolve effective defense mechanisms. Fortunately, alternative therapies exist and, at the forefront of research lays the photodynamic inhibition approach mediated by porphyrin based photosensitizers. This review will focus on the development of various porphyrins compounds and their incorporation as small molecules, into polymers, fibers and thin films as practical therapeutic agents, utilizing photodynamic therapy to inhibit a wide spectrum of bacterium. The use of photodynamic therapy of these porphyrin molecules are discussed and evaluated according to their electronic and bulk material effect on different bacterium strains. This review also provides an insight into the general direction and challenges facing porphyrins and derivatives as full-fledged therapeutic agents and what needs to be further done in order to be bestowed their rightful and equal status in modern medicine, similar to the very first antibiotic; penicillin itself. It is hoped that, with this perspective, new paradigms and strategies in the application of porphyrins and derivatives will progressively flourish and lead to advances against disease. PMID- 27276372 TI - Implications of oxidative stress in the brain plasticity originated by fasting: a BOLD-fMRI study. AB - OBJECTIVES: The goal of this study was assessing the intermittent fasting effect on brain plasticity and oxidative stress (OS) using blood-oxygenation-level dependent (BOLD)-functional magnetic resonance image (fMRI) approach. Evidences of physiological and molecular phenomena involved in this process are discussed and compared to reported literature. METHOD: Six fully healthy male non-smokers volunteered in this study. All volunteers were right handed, and have an equilibrated, consistent and healthy daily nutritional habit, and a healthy lifestyle. Participants were allowed consuming food during evening and night time while fasting with self-prohibiting food and liquids during 14 hours/day from sunrise to sunset. All participants underwent identical brain BOLD-fMRI protocol. The images were acquired in the Department of Radiology and Clinical Imaging of the University Hospital of Fez, Fez, Morocco. The anatomical brain and BOLD-fMRIs were acquired using a 1.5-Tesla scanner (Signa, General Electric, Milwaukee, United States). BOLD-fMRI image acquisition was done using single-shot gradient echo echo-planer imaging sequence. BOLD-fMRI paradigm consisted of the motor task where volunteers were asked to perform finger taping of the right hand. Two BOLD fMRI scan sessions were performed, the first one between the 5th and 10th days preceding the start of fasting and the second between days 25th and 28th of the fasting month. All sessions were performed between 3:30 PM and 5:30 PM. Although individual maps were originated from different individual participants, they cover the same anatomic area in each case. Image processing and statistical analysis were conducted with Statistical Parameter Mapping version 8 (2008, Welcome Department of Cognitive Neurology, London UK). RESULTS AND DISCUSSION: The maximal BOLD signal changes were calculated for each subject in the motor area M1; Activation maps were calculated and overlaid on the anatomical images. Group analysis of the data was performed, and the average volume and the maximum intensity of BOLD signal in the activated area M1 was determined for all studied volunteers. The current study allowed measuring regional brain volumes and neural network activity before and during an extended period of fasting using BOLD-fMRI. This demonstrated and confirmed the impact of fasting on human brain structure and function. Further studies are required to elucidate mechanisms and enable direct inference of a diet-induced OS effect on the brain. PMID- 27276374 TI - Floristic evolution in an agroforestry system cultivation in Southern Brazil. AB - Bracatinga (Mimosa scabrella Bentham) is an important pioneer tree species in Ombrophylous Mixed Forest of Brazil and is widely used as an energy source. In traditional agroforestry systems, regeneration is induced by fire, then pure and dense stands known as bracatinga stands (bracatingais) are formed. In the first year, annual crops are intercalated with the seedlings. At that time the seedlings are thinned, then the stands remain at a fallow period and cut at seven years old. The species is very important mainly for small landowners. We studied the understory species that occur naturally during the succession over several years in order to manage them rationally in the future and maintain the natural vegetation over time. Three to 20 year-old Bracatinga stands were sampled between 1998 and 2011. All tree species with diameter at breast height (DBH) >= 5 cm were measured.The floristic evolution was assessed with respect to Sociability Index, the Shannon Diversity Index and the Pielou Evenness Index. Graphs of rank/abundance over different age groups were evaluated using the Kolmogorov Smirnov test. We identified 153 species dispersed throughout the understory and tend to become aggregated over time. PMID- 27276373 TI - Optimizing Treatment of Complicated Grief: A Randomized Clinical Trial. AB - IMPORTANCE: To our knowledge, this is the first placebo-controlled randomized clinical trial to evaluate the efficacy of antidepressant pharmacotherapy, with and without complicated grief psychotherapy, in the treatment of complicated grief. OBJECTIVE: To confirm the efficacy of a targeted complicated grief treatment (CGT), determine whether citalopram (CIT) enhances CGT outcome, and examine CIT efficacy without CGT. DESIGN, SETTING, AND PARTICIPANTS: Included in the study were 395 bereaved adults who met criteria for CG recruited from March 2010 to September 2014 from academic medical centers in Boston, Massachusetts; New York, New York; Pittsburgh, Pennsylvania; and San Diego, California. Co occurring substance abuse, psychosis, mania, and cognitive impairment were exclusionary. Study participants were randomized using site-specific permuted blocks stratified by major depression into groups prescribed CIT (n = 101), placebo (PLA; n = 99), CGT with CIT (n = 99), and CGT with PLA (n = 96). Independent evaluators conducted monthly assessments for 20 weeks. Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting. INTERVENTIONS: All participants received protocolized pharmacotherapy optimized by flexible dosing, psychoeducation, grief monitoring, and encouragement to engage in activities. Half were also randomized to receive manualized CGT in 16 concurrent weekly sessions. MAIN OUTCOMES AND MEASURES: Complicated grief anchored Clinical Global Impression scale measurments every 4 weeks. Response was measured as a rating of "much improved" or "very much improved." RESULTS: Of the 395 study participants, 308 (78.0%) were female and 325 (82.3%) were white. Participants' response to CGT with PLA vs PLA (82.5% vs 54.8%; relative risk [RR], 1.51; 95% CI, 1.16-1.95; P = .002; number needed to treat [NNT], 3.6) suggested the efficacy of CGT, and the addition of CIT did not significantly improve CGT outcome (CGT with CIT vs CGT with PLA: 83.7% vs 82.5%; RR, 1.01; 95% CI, 0.88-1.17; P = .84; NNT, 84). However, depressive symptoms decreased significantly more when CIT was added to treatment (CGT with CIT vs CGT with PLA: model-based adjusted mean [standard error] difference, -2.06 [1.00]; 95% CI, 4.02 to -0.11; P = .04). By contrast, adding CGT improved CIT outcome (CIT vs CGT with CIT: 69.3% vs 83.7%; RR, 1.21; 95% CI, 1.00-1.46; P = .05; NNT, 6.9). Last, participant response to CIT was not significantly different from PLA at week 12 (45.9% vs 37.9%; RR, 1.21; 95% CI, 0.82-1.81; P = .35; NNT, 12.4) or at week 20 (69.3% vs 54.8%; RR, 1.26; 95% CI, 0.95-1.68; P = .11; NNT, 6.9). Rates of suicidal ideation diminished to a substantially greater extent among participants receiving CGT than among those who did not. CONCLUSIONS AND RELEVANCE: Complicated grief treatment is the treatment of choice for CG, and the addition of CIT optimizes the treatment of co-occurring depressive symptoms. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01179568. PMID- 27276375 TI - Equilibrium pricing and ordering policies in a two-echelon supply chain in the presence of strategic customers. AB - This paper studying the impact of strategic customer behavior on decentralized supply chain gains and decisions, which includes a supplier, and a monopoly firm as a retailer who sells a single product over a finite two periods of selling season. We consider three types of customers: myopic, strategic and low-value customers. The problem is formulated as a bi-level game where at the second level (e.g. horizontal game), the retailer determines his/her equilibrium pricing strategy in a non-cooperative simultaneous general game with strategic customers who choose equilibrium purchasing strategy to maximize their expected surplus. At the first level (e.g. vertical game), the supplier competes with the retailer as leader and follower in the Stackelberg game. They set the wholesale price and initial stocking capacity to maximize their profits. Finally, a numerical study is presented to demonstrate the impacts of strategic behavior on supply chain gain and decisions; subsequently the effects of market parameters on decision variables and total profitability of supply chain's members is studied through a sensitivity analysis. PMID- 27276376 TI - Regarding the real diversity of Glyptodontidae (Mammalia, Xenarthra) in the late Pliocene (Chapadmalalan Age/Stage) of Argentina. AB - A large diversity of Glyptodontidae has been proposed as characterizing the Chapadmalalan Age (Pliocene). Most of these taxa were recognized on the basis of partial dorsal carapaces and/or caudal tubes, whereas the main diagnostic characteristic is a particular morphology of the exposed surface of the osteoderms. From a biostratigraphic point of view some species are biostratigraphically important. The Upper Chapadmalalan is based on the Paraglyptodon chapadmalensis biozone. Both the re-evaluation of the type and referred materials and new significant findings from the Chapadmalal and El Polvorin Formations indicate that the diversity of Pliocene Glyptodontidae is more limited than previously supposed. The particular morphology of the exposed surface of the osteoderms that characterizes some of the species actually corresponds to a taphonomic alteration, which results in a non-real ornamentation pattern. Thus, the Glyptodontinae P. chapadmalensis must be replaced as a fossil guide because neither this species nor the species included in the genera Urotherium, Trachycalyptus and Lomaphorus are well characterized. Taking into account the diversity of Glyptodontidae for this lapse, the Glyptodontinae are very scarce (a situation that contrasts with its records in the Pleistocene), whereas Eosclerocalyptus, "Plohophorini" (Plohophorus) and Doedicurinae (cf. Eleutherocercus antiquus) are among the most recorded taxa. PMID- 27276377 TI - Late Pleistocene echimyid rodents (Rodentia, Hystricognathi) from northern Brazil. AB - Echimyidae (spiny rats, tree rats and the coypu) is the most diverse family of extant South American hystricognath rodents (caviomorphs). Today, they live in tropical forests (Amazonian, coastal and Andean forests), occasionally in more open xeric habitats in the Cerrado and Caatinga of northern South America, and open areas across the southern portion of the continent (Myocastor). The Quaternary fossil record of this family remains poorly studied. Here, we describe the fossil echimyids found in karst deposits from southern Tocantins, northern Brazil. The analyzed specimens are assigned to Thrichomys sp., Makalata cf. didelphoides and Proechimys sp. This is the first time that a fossil of Makalata is reported. The Pleistocene record of echimyids from this area is represented by fragmentary remains, which hinders their determination at specific levels. The data reported here contributes to the understanding of the ancient diversity of rodents of this region, evidenced until now in other groups, such as the artiodactyls, cingulates, carnivores, marsupials, and squamate reptiles. PMID- 27276378 TI - Relevance of Hydrodynamic Effects for the Calculation of Outer Surface Potential of Biological Membrane Using Electrophoretic Data. AB - In this paper, we present the results of a study on the influence of hydrodynamic effects on the surface potentials of the erythrocyte membrane, comparing two different models formulated to simulate the electrophoretic movement of a biological cell: the classical Helmholtz-Smoluchowski model and a model presented by Hsu et al. (1996). This model considers hydrodynamic effects to describe the distribution of the fluid velocity. The electric potential equation was obtained from the non-linear Poisson-Boltzmann equation, considering the spatial distribution of electrical charges fixed in glycocalyx and cytoplasmic proteins, as well as electrolyte charges and ones fixed on the surfaces of lipidic bilayer. Our results show that the Helmholtz-Smoluchowski model is not able to reflect the real forces responsible to the electrophoretic behavior of cell, because it does not take account the hydrodynamic effects of glycocalyx. This charged network that covers cellular surface constitutes a complex physical system whose electromechanical characteristics cannot be neglected. Then, supporting the hypothesis of other authors, we suggest that, in electrophoretic motion analyses of cells, the classical model represents a limiting case of models that take into account hydrodynamic effects to describe the velocity distribution of fluid. PMID- 27276379 TI - An examination of soil and water conservation practices in the paddy fields of Guilan province, Iran. AB - This study examined the use of soil and water conservation (SWC) practices among rice farmers in Iran. A random sample of 400 rice paddy farmers in the Foumanat plain of Guilan province, who use SWC measures, was drawn from a population of 52 thousand farmers. A two-part questionnaire was used to examine the level of utilization of SWC practices and to profile paddy farmers. Internal consistency was demonstrated with a coefficient alpha of 0.76, and the content and face validity of the instrument was confirmed by a panel of soil and water experts. Descriptive and analytical statistics were used to analyze the data. Results of ANOVA indicated that the mean levels of SWC practices vary considerably at the 0.01 level of significance by groups of age, education, non-agricultural income, production costs, yield, cultivated paddies and distance from home to the farm or to the main road. Similarly, significant differences were observed by groups of family size, rice production, ownership of livestock and profits from rice production at 0.05 level. The levels of experience in agriculture and ownership of poultry were found to have no significant effects on SWC practices. PMID- 27276380 TI - Scientists in the public sphere: Interactions of scientists and journalists in Brazil. AB - In order to map scientists' views on media channels and explore their experiences interacting with journalists, the authors conducted a survey of about 1,000 Brazilian scientists. Results indicate that scientists have clear and high expectations about how journalists should act in reporting scientific information in the media, but such expectations, in their opinion, do not always seem to be met. Nonetheless, the results show that surveyed scientists rate their relation with the media positively: 67% say that having their research covered by media has a positive impact on their colleagues. One quarter of the respondents expressed that talking to the media can facilitate acquisition of more funds for research. Moreover, 38% of the total respondents believe that writing about an interesting topic for release on media channels can also facilitate research publication in a scientific journal. However, 15% of the respondents outright agree that research reported in the media beforehand can threaten acceptance for publication by a scientific journal. We hope that these results can foster some initiatives for improving awareness of the two cultures, scientists and journalists; increasing the access of journalists to Brazilian scientific endeavors; stimulating scientists to communicate with the public via social networks. PMID- 27276381 TI - Dating of fossil human teeth and shells from Toca do Enoque site at Serra das Confusoes National Park, Brazil. AB - This work reports the dating of a fossil human tooth and shell found at the archaeological site Toca do Enoque located in Serra das Confusoes National Park (Piaui, Brazil). Many prehistoric paintings have been found at this site. An archaeological excavation unearthed three sepulchers with human skeletons and some shells. Two Brazilian laboratories, in Ribeirao Preto (USP) and Recife (UFPE), independently performed Electron Spin Resonance (ESR) measurements to date the tooth and the shell and obtain the equivalent dose received by each sample. The laboratories determined similar ages for the tooth and the shell (~4.8 kyBP). The results agreed with C-14 dating of the shell and other samples (charcoal) collected in the same sepulcher. Therefore, this work provides a valid inter-comparison of results by two independent ESR-dating laboratories and between two dating methods; i.e., C-14 and ESR, showing the validity of ESR dating for this range of ages. PMID- 27276382 TI - Physico-chemical and sensory evaluation of potato (Solanum tuberosum L.) after irradiation. AB - This work evaluated the effects of ionizing radiation on the physico-chemical and sensory characteristics of the potato cultivar Agata (Solanum tuberosum L.), including budding and deterioration, with the end goal of increasing shelf life. For this, four groups of samples were harvested at the maturation stage. Three of them were separately exposed to a Co-60 source, receiving respective doses of 0.10, 0.15 and 2.00 kGy, while the non-irradiated group was kept as a control. All samples were stored for 35 days at 24 degrees C (+/- 2) and at 39% relative humidity. The following aspects were evaluated: budding, rot, loss of weight, texture, flesh color, moisture, external and internal appearance, aroma, soluble solids, titratable acidity, vitamin C, protein, starch and glucose. The results indicated that 0.15 kGy was the most effective dose to reduce sprouting and post harvest losses, under the conditions studied. PMID- 27276383 TI - Mesoporous Bamboo Charcoal Nanoparticles as a New Near-Infrared Responsive Drug Carrier for Imaging-Guided Chemotherapy/Photothermal Synergistic Therapy of Tumor. AB - Near-infrared-(NIR)-light-triggered photothermal nanocarriers have attracted much attention for the construction of more smart and effective therapeutic platforms in nanomedicine. Here, a multifunctional drug carrier based on a low cost, natural, and biocompatible material, bamboo charcoal nanoparticles (BCNPs), which are prepared by the pyrolysis of bamboo followed by physical grinding and ultrasonication is reported. The as-prepared BCNPs with porous structure possess not only large surface areas for drug loading but also an efficient photothermal effect, making them become both a suitable drug carrier and photothermal agent for cancer therapy. After loading doxorubicin (DOX) into the BCNPs, the resulting DOX-BCNPs enhance drug potency and more importantly can overcome the drug resistance of DOX in a MCF-7 cancer cell model by significantly increasing cellular uptake while remarkably decreasing drug efflux. The in vivo synergistic effect of combining chemotherapy and photothermal therapy in this drug delivery system is also demonstrated. In addition, the BCNPs enhance optoacoustic imaging contrast due to their high NIR absorbance. Collectively, it is demonstrated that the BCNP drug delivery system constitutes a promising and effective nanocarrier for simultaneous bioimaging and chemo-photothermal synergistic therapy of cancer. PMID- 27276384 TI - Ruthenium-Catalyzed Oxidative Homocoupling of Arylboronic Acids in Water: Ligand Tuned Reactivity and Mechanistic Study. AB - Molecular catalysts based on water-soluble arene-Ru(II) complexes ([Ru]-1-[Ru]-5) containing aniline (L1), 2-methylaniline (L2), 2,6-dimethylaniline (L3), 4 methylaniline (L4), and 4-chloroaniline (L5) were designed for the homocoupling of arylboronic acids in water. These complexes were fully characterized by (1)H, (13)C NMR, mass spectrometry, and elemental analyses. Structural geometry for two of the representative arene-Ru(II) complexes [Ru]-3 and [Ru]-4 was established by single-crystal X-ray diffraction studies. Our studies showed that the selectivity toward biaryls products is influenced by the position and the electronic behavior of various substituents of aniline ligand coordinated to ruthenium. Extensive investigations using (1)H NMR, (19)F NMR, and mass spectral studies provided insights into the mechanistic pathway of homocoupling of arylboronic acids, where the identification of important organometallic intermediates, such as sigma aryl/di(sigma-aryl) coordinated arene-Ru(II) species, suggested that the reaction proceeds through the formation of crucial di(sigma-aryl)-Ru intermediates by the interaction of arylboronic acid with Ru-catalyst to yield biaryl products. PMID- 27276385 TI - Palladium/Silver Synergistic Catalysis in Direct Aerobic Carbonylation of C(sp(2))-H Bonds Using DMF as a Carbon Source: Synthesis of Pyrido-Fused Quinazolinones and Phenanthridinones. AB - An unprecedented Pd/Ag synergistic catalysis in the direct carbonylation of C(sp(2))-H bonds utilizing DMF as the carbon source under oxygen is described and demonstrated in the synthesis of pyrido-fused quinazolinone and phenanthridinone scaffolds. Control experiments indicated that the "C" of the carbonyl group is derived from the methyl group of DMF and "O" originates from oxygen as in the case of Ge's recent work. This transformation offers an alternative avenue for "CO-free" carbonylations. PMID- 27276386 TI - Prison Experiences and Psychological Distress among Older Inmates. AB - This study investigates relationships between older prisoners' social experiences and their levels of distress. One hundred and seventy-three older prisoners (aged >= 50 years) from 8 Australian prisons were administered the Kessler Psychological Distress (K10) Scale, with additional information collected via individual interviews. Psychological distress scores were significantly associated with measures of self-reported safety (p < .001), prison victimization (p < .05), perceived social support from staff (p < .01) and inmates (p < .001), current employment (p < .05), and level of exercise (p < .001) among older inmates. Findings suggest that strategies for improving sense of safety, social support and level of exercise may ameliorate distress among older prisoners. PMID- 27276387 TI - Quasi-Block Copolymers Based on a General Polymeric Chain Stopper. AB - Quasi-block copolymers (q-BCPs) are block copolymers consisting of conventional and supramolecular blocks, in which the conventional block is end-terminated by a functionality that interacts with the supramolecular monomer (a "chain stopper" functionality). A new design of q-BCPs based on a general polymeric chain stopper, which consists of polystyrene end-terminated with a sulfonate group (PS SO3 Li), is described. Through viscosity measurements and a detailed diffusion ordered NMR spectroscopy study, it is shown that PS-SO3 Li can effectively cap two types of model supramolecular monomers to form q-BCPs in solution. Furthermore, differential scanning calorimetry data and structural characterization of thin films by scanning force microscopy suggests the existence of the q-BCP architecture in the melt. The new design considerably simplifies the synthesis of polymeric chain stoppers; thus promoting the utilization of q-BCPs as smart, nanostructured materials. PMID- 27276388 TI - Is There a Role for PET/CT Parameters to Characterize Benign, Malignant, and Metastatic Parotid Tumors? AB - OBJECTIVE: Assessment of benign and malignant lesions of the parotid gland, including metastatic lesions, is challenging with current imaging methods. Fluorine-18 FDG PET/CT is a noninvasive imaging modality that provides both anatomic and metabolic information. Semiquantitative data obtained from PET/CT, also known as PET/CT parameters, are maximum, mean, or peak standardized uptake values (SUVs); metabolic tumor volume; total lesion glycolysis; standardized added metabolic activity; and normalized standardized added metabolic activity. Our aim was to determine whether FDG PET/CT parameters can differentiate benign, malignant, and metastatic parotid tumors. MATERIALS AND METHODS: Thirty-four patients with parotid neoplasms underwent PET/CT before parotidectomy; maximum SUV, mean SUV, peak SUV, total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity were calculated on a dedicated workstation. Univariate analyses were performed. A ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven benign, malignant, and metastatic parotid gland neoplasms. RESULTS: Fourteen patients had a benign or malignant primary parotid tumor. Twenty had metastases to the parotid gland. When the specificity was set to at least 85% for each parameter to identify cut points, the corresponding sensitivities ranged from 15% to 40%. Assessment of benign versus malignant lesions of parotid tumors, as well as metastasis from squamous cell carcinoma versus other metastatic causes, revealed that none of the PET/CT parameters has enough power to differentiate among these groups. CONCLUSION: PET/CT parameters, including total lesion glycolysis, metabolic tumor volume, standardized added metabolic activity, and normalized standardized added metabolic activity, are not able to differentiate benign from malignant parotid tumors, primary parotid tumors from metastasis, or metastasis from squamous cell carcinoma and nonsquamous cell carcinoma metastasis. PMID- 27276390 TI - Computing Average Passive Forces in Sarcomeres in Length-Ramp Simulations. AB - Passive forces in sarcomeres are mainly related to the giant protein titin. Titin's extensible region consists of spring-like elements acting in series. In skeletal muscles these elements are the PEVK segment, two distinct immunoglobulin (Ig) domain regions (proximal and distal), and a N2A portion. While distal Ig domains are thought to form inextensible end filaments in intact sarcomeres, proximal Ig domains unfold in a force- and time-dependent manner. In length-ramp experiments of single titin strands, sequential unfolding of Ig domains leads to a typical saw-tooth pattern in force-elongation curves which can be simulated by Monte Carlo simulations. In sarcomeres, where more than a thousand titin strands are arranged in parallel, numerous Monte Carlo simulations are required to estimate the resultant force of all titin filaments based on the non-uniform titin elongations. To simplify calculations, the stochastic model of passive forces is often replaced by linear or non-linear deterministic and phenomenological functions. However, new theories of muscle contraction are based on the hypothesized binding of titin to the actin filament upon activation, and thereby on a prominent role of the structural properties of titin. Therefore, these theories necessitate a detailed analysis of titin forces in length-ramp experiments. In our study we present a simple and efficient alternative to Monte Carlo simulations. Based on a structural titin model, we calculate the exact probability distributions of unfolded Ig domains under length-ramp conditions needed for rigorous analysis of expected forces, distribution of unfolding forces, etc. Due to the generality of our model, the approach is applicable to a wide range of stochastic protein unfolding problems. PMID- 27276389 TI - On- and Off-Cycle Catalyst Cooperativity in Anion-Binding Catalysis. AB - Chiral, neutral H-bond donors have found widespread use as catalysts in enantioselective reactions involving ion-pair intermediates. Herein, a systematic mechanistic study of a prototypical anion-binding reaction, the thiourea catalyzed enantioselective alkylation of alpha-chloroethers, is detailed. This study reveals that the catalyst resting state is an inactive dimeric aggregate that must dissociate and then reassemble to form a 2:1 catalyst-substrate complex in the rate-determining transition structure. Insight into this mode of catalyst cooperativity sheds light on the practical limitations that have plagued many of the H-bond donor-catalyzed reactions developed to date and suggests design strategies for new, highly efficient catalyst structures. PMID- 27276391 TI - Biomechanical Behaviors in Three Types of Spinal Cord Injury Mechanisms. AB - Clinically, spinal cord injuries (SCIs) are radiographically evaluated and diagnosed from plain radiographs, computed tomography (CT), and magnetic resonance imaging. However, it is difficult to conclude that radiographic evaluation of SCI can directly explain the fundamental mechanism of spinal cord damage. The von-Mises stress and maximum principal strain are directly associated with neurological damage in the spinal cord from a biomechanical viewpoint. In this study, the von-Mises stress and maximum principal strain in the spinal cord as well as the cord cross-sectional area (CSA) were analyzed under various magnitudes for contusion, dislocation, and distraction SCI mechanisms, using a finite-element (FE) model of the cervical spine with spinal cord including white matter, gray matter, dura mater with nerve roots, and cerebrospinal fluid (CSF). A regression analysis was performed to find correlation between peak von-Mises stress/peak maximum principal strain at the cross section of the highest reduction in CSA and corresponding reduction in CSA of the cord. Dislocation and contusion showed greater peak stress and strain values in the cord than distraction. The substantial increases in von-Mises stress as well as CSA reduction similar to or more than 30% were produced at a 60% contusion and a 60% dislocation, while the maximum principal strain was gradually increased as injury severity elevated. In addition, the CSA reduction had a strong correlation with peak von-Mises stress/peak maximum principal strain for the three injury mechanisms, which might be fundamental information in elucidating the relationship between radiographic and mechanical parameters related to SCI. PMID- 27276392 TI - The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China. AB - OBJECTIVE: This study investigated the correlation between the albumin-to creatinine ratio in the urine and 24-hour urine proteinuria and whether the ratio can predict chronic kidney disease progression even more reliably than 24-hour proteinuria can, particularly in primary IgA nephropathy. METHODS: A total of 182 patients with primary IgA nephropathy were evaluated. Their mean urine albumin-to creatinine ratio and 24-hour proteinuria were determined during hospitalization. Blood samples were also analyzed. Follow-up data were recorded for 44 patients. A cross-sectional study was then conducted to test the correlation between these parameters and their associations with chronic kidney disease complications. Subsequently, a canonical correlation analysis was employed to assess the correlation between baseline proteinuria and parameters of the Oxford classification. Finally, a prospective observational study was performed to evaluate the association between proteinuria and clinical outcomes. Our study is registered in the Chinese Clinical Trial Registry, and the registration number is ChiCTR-OCH-14005137. RESULTS: A strong correlation (r=0.81, p<0.001) was found between the ratio and 24-hour proteinuria except in chronic kidney disease stage 5. First-morning urine albumin-to-creatinine ratios of >=125.15, 154.44 and 760.31 mg/g reliably predicted equivalent 24-hour proteinuria 'thresholds' of >=0.15, 0.3 and 1.0 g/24 h, respectively. In continuous analyses, the albumin-to creatinine ratio was significantly associated with anemia, acidosis, hypoalbuminemia, hyperphosphatemia, hyperkalemia, hypercholesterolemia and higher serum cystatin C. However, higher 24-hour proteinuria was only associated with hypoalbuminemia and hypercholesterolemia. Higher tubular atrophy and interstitial fibrosis scores were also associated with a greater albumin-to-creatinine ratio, as observed in the canonical correlation analysis. Finally, the albumin-to creatinine ratio and 24-hour proteinuria were associated with renal outcomes in univariate analyses. CONCLUSION: This study supports the recommendation of using the albumin-to-creatinine ratio, rather than 24-hour proteinuria, to monitor proteinuria and prognosis in primary IgA nephropathy. PMID- 27276393 TI - The serum matrix metalloproteinase-9 level is an independent predictor of recurrence after ablation of persistent atrial fibrillation. AB - OBJECTIVES: This study investigated whether the serum matrix metalloproteinase-9 level is an independent predictor of recurrence after catheter ablation for persistent atrial fibrillation. METHODS: Fifty-eight consecutive patients with persistent atrial fibrillation were enrolled and underwent catheter ablation. The serum matrix metalloproteinase-9 level was detected before ablation and its relationship with recurrent arrhythmia was analyzed at the end of the follow-up. RESULTS: After a mean follow-up of 12.1+/-7.2 months, 21 (36.2%) patients had a recurrence of their arrhythmia after catheter ablation. At baseline, the matrix metalloproteinase-9 level was higher in the patients with recurrence than in the non-recurrent group (305.77+/-88.90 vs 234.41+/-93.36 ng/ml, respectively, p=0.006). A multivariate analysis showed that the matrix metalloproteinase-9 level was an independent predictor of arrhythmia recurrence, as was a history of atrial fibrillation and the diameter of the left atrium. CONCLUSION: The serum matrix metalloproteinase-9 level is an independent predictor of recurrent arrhythmia after catheter ablation in patients with persistent atrial fibrillation. PMID- 27276394 TI - The relationship between serum albumin levels and 24-h ambulatory blood pressure monitoring recordings in non-diabetic essential hypertensive patients. AB - OBJECTIVES: The goal of this study was to evaluate the relationship between serum albumin levels and 24-hour ambulatory blood pressure monitoring (24-h ABPM) recordings in non-diabetic essential hypertensive patients. METHODS: A total of 354 patients (mean [SD] age: 55.5 [14.3] years, 50% females) with essential hypertension and 24-h ABPM recordings were included. Patient 24-h nighttime and daytime ABPM values, systolic and diastolic dipping status and average nocturnal dipping were recorded. The correlations between serum albumin levels and nocturnal systolic and diastolic dipping were evaluated, and correlates of average nocturnal systolic dipping were determined via a linear regression model. RESULTS: Overall, 73.2% of patients were determined to be non-dippers. The mean (SD) levels of serum albumin (4.2 [0.3] g/dL vs. 4.4 [0.4] g/dL, p<0.001) and the average nocturnal systolic (15.2 [4.8] mmHg vs. 0.3 [6.6] mmHg, p<0.001) and diastolic dipping (4.2 [8.6] mmHg vs. 18.9 [7.0] mmHg, p<0.001) were significantly lower in non-dippers than in dippers. A significant positive correlation was noted between serum albumin levels and both systolic (r=0.297, p<0.001) and diastolic dipping (r=0.265, p<0.001). The linear regression analysis revealed that for each one-unit increase in serum albumin, the average nocturnal dip in systolic BP increased by 0.17 mmHg (p=0.033). CONCLUSION: Our findings indicate an association between serum albumin levels and the deterioration of circadian BP rhythm among essential hypertensive patients along with the identification of a non-dipper pattern in more than two-thirds of patients. Our findings emphasize the importance of serum albumin levels, rather than urinary albumin excretion, as an independent predictor of nocturnal systolic dipping, at least in non-diabetic essential hypertensive patients with moderate proteinuria. PMID- 27276395 TI - Efficacy and safety of a NiTi CAR 27 compression ring for end-to-end anastomosis compared with conventional staplers: A real-world analysis in Chinese colorectal cancer patients. AB - OBJECTIVES: This study aimed to evaluate the safety and efficacy of a new nickel titanium shape memory alloy compression anastomosis ring, NiTi CAR 27, in constructing an anastomosis for colorectal cancer resection compared with conventional staples. METHODS: In total, 234 consecutive patients diagnosed with colorectal cancer receiving sigmoidectomy and anterior resection for end-to-end anastomosis from May 2010 to June 2012 were retrospectively analyzed. The postoperative clinical parameters, postoperative complications and 3-year overall survival in 77 patients using a NiTi CAR 27 compression ring (CAR group) and 157 patients with conventional circular staplers (STA group) were compared. RESULTS: There were no statistically significant differences between the patients in the two groups in terms of general demographics and tumor features. A clinically apparent anastomotic leak occurred in 2 patients (2.6%) in the CAR group and in 5 patients (3.2%) in the STA group (p=0.804). These eight patients received a temporary diverting ileostomy. One patient (1.3%) in the CAR group was diagnosed with anastomotic stricture through an electronic colonoscopy after 3 months postoperatively. The incidence of postoperative intestinal obstruction was comparable between the two groups (p=0.192). With a median follow-up duration of 39.6 months, the 3-year overall survival rate was 83.1% in the CAR group and 89.0% in the STA group (p=0.152). CONCLUSIONS: NiTi CAR 27 is safe and effective for colorectal end-to-end anastomosis. Its use is equivalent to that of the conventional circular staplers. This study suggests that NiTi CAR 27 may be a beneficial alternative in colorectal anastomosis in Chinese colorectal cancer patients. PMID- 27276396 TI - Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space. AB - OBJECTIVES: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics. METHODS: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1) patients with Gram-negative bacterial infections, aged 53.2+/-18.6 years old, of whom 44.7% had empyemas and 2) patients with Gram-positive bacterial infections, aged 53.5+/-21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman's correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase. RESULTS: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8+/-32.1 U/L vs 81.0+/-16.9 U/L, p<0.01). The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01) at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%); a specificity of 73.7% (56.9 86.6%); positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively. CONCLUSIONS: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the pleural space, which is useful for the selection of antibiotics. PMID- 27276397 TI - Randomized clinical trial comparing lumbar percutaneous hydrodiscectomy with lumbar open microdiscectomy for the treatment of lumbar disc protrusions and herniations. AB - OBJECTIVES: Hydrodiscectomy is a new technique used for percutaneous spinal discectomy that employs a high-intensity stream of water for herniated disc ablation and tissue aspiration. No previous clinical study has examined the effects of percutaneous hydrodiscectomy. The aim of this study is to evaluate the outcomes of hydrodiscectomy compared to open microdiscectomy regarding pain, function, satisfaction, complications and recurrence rates. METHODS: In this randomized clinical trial, patients referred to our tertiary hospital for lumbar back pain were recruited and included in the study if they had disc protrusion or small herniation in only one level, without neurological deficits and with no resolution after six weeks of conservative treatment. One group underwent open microdiscectomy, and the other group underwent percutaneous microdiscectomy via hydrosurgery. Function was evaluated using the Oswestry Disability Index and pain was assessed using a visual analog scale. Evaluations were performed preoperatively, and then during the first week and at one, three, six and twelve months postoperatively. Personal satisfaction was verified. Clinicaltrials.gov: NCT01367860. RESULTS: During the study period, 20 patients were included in each arm and 39 completed one-year of follow-up (one patient died of unrelated causes). Both groups exhibited equal improvement on the visual analog scale and Oswestry evaluations after treatment, without any significant differences. The improvement in the lumbar visual analog scale score was not significant in the hydrodiscectomy group (p=0.138). The rates of infection, pain, recurrence and satisfaction were similar between the two groups. CONCLUSION: Percutaneous hydrodiscectomy was demonstrated to be as effective as open microdiscectomy for reducing pain. The rates of complications and recurrence of herniation were similar between groups. Patient satisfaction with the treatment was also similar between groups. PMID- 27276399 TI - Is the difference in the volume of the pharyngeal space, as measured by acoustic pharyngometry, before and after tonsillectomy proportional to the volume of the excised tonsils? AB - OBJECTIVE: Adenotonsillectomy is recognized as an effective therapy for snoring and sleep disorders in children. It is important to understand whether adenotonsillectomy significantly increases the volume of the pharyngeal space. The goal of this study was to evaluate the change in oropharyngeal volume after adenotonsillectomy and the correlation of this change with the objective volume of the tonsils and body mass index. METHODS: We included 27 subjects (14 males) with snoring caused by tonsil and adenoid hypertrophy. The mean age of the subjects was 7.92 (+/-2.52) years. Children with craniofacial malformations or neuromuscular diseases or syndromes were excluded. The parents/caregivers answered an adapted questionnaire regarding sleep-disordered breathing. All patients were subjected to weight and height measurements and body mass index was calculated. The subjects underwent pharyngometry before and after adenotonsillectomy and the volume of both excised tonsils together was measured in cm3 in the operating room. RESULTS: Pharyngometric analysis showed that the mean pharyngeal volume was 28.63 (+/-5.57) cm3 before surgery and 31.23 (+/-6.76) cm3 after surgery; the volume of the oropharynx was significantly increased post surgery (p=0.015, Wilcoxon test). No correlation was found between the objective tonsil volume and the post-surgical volume increase (p=0.6885). There was a fair correlation between the oropharyngeal volume and body mass index (p=0.0224). CONCLUSION: Adenotonsillectomy increases the volume of the pharyngeal space, but this increase does not correlate with the objective tonsil size. Furthermore, greater BMI was associated with a smaller increase in the pharyngeal volume. Oropharyngeal structures and craniofacial morphology may also play a role in the increase in oropharyngeal volume. PMID- 27276398 TI - Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey. AB - OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day) and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases' 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, Sao Paulo, Parana and Rio Grande do Sul). The mean age was 67+/-11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3), in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, >=3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in patients with and without cirrhosis in Brazil. In this survey, hepatocellular carcinoma was observed in elevated numbers of patients with steatohepatitis without cirrhosis. PMID- 27276400 TI - Effect of a gel containing pilocarpine on vaginal atrophy in castrated rats. AB - OBJECTIVES: To evaluate the effect of Carbopol gel formulations containing pilocarpine on the morphology and morphometry of the vaginal epithelium of castrated rats. METHODS: Thirty-one female Wistar-Hannover rats were randomly divided into four groups: the control Groups I (n=7, rats in persistent estrus; positive controls) and II (n=7, castrated rats, negative controls) and the experimental Groups, III (n=8) and IV (n=9). Persistent estrus (Group I) was achieved with a subcutaneous injection of testosterone propionate on the second postnatal day. At 90 days postnatal, rats in Groups II, III and IV were castrated and treated vaginally for 14 days with Carbopol gel (vehicle alone) or Carbopol gel containing 5% and 15% pilocarpine, respectively. Next, all of the animals were euthanized and their vaginas were removed for histological evaluation. A non parametric test with a weighted linear regression model was used for data analysis (p<0.05). RESULTS: The morphological evaluation showed maturation of the vaginal epithelium with keratinization in Group I, whereas signs of vaginal atrophy were present in the rats of the other groups. Morphometric examinations showed mean thickness values of the vaginal epithelium of 195.10+/-12.23 MUm, 30.90+/-1.14 MUm, 28.16+/-2.98 MUm and 29.84+/-2.30 MUm in Groups I, II, III and IV, respectively, with statistically significant differences between Group I and the other three groups (p<0.0001) and no differences between Groups II, III and IV (p=0.0809). CONCLUSION: Topical gel formulations containing pilocarpine had no effect on atrophy of the vaginal epithelium in the castrated female rats. PMID- 27276401 TI - Adjunctive alpha-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double blind randomized placebo-controlled study. AB - alpha-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics. PMID- 27276403 TI - Special Edition for Anthropology and Medicine Biomedical Technology and Health Inequities in the Global North and South. PMID- 27276404 TI - Technologies of hope? Motherhood, HIV and infant feeding in eastern Africa. AB - A vast number of HIV positive mothers live with a known HIV positive status without an experienced ability to prevent the virus from spreading to their offspring. This article focuses on the dramatic effects on identity and sociality instigated by prevention of mother to child transmission of HIV (PMTCT) programmes, and discusses the potential for the development of HIV related activism linked to programme enrolment. Paying particular attention to the infant feeding options that are promoted through the programme - exclusive breastfeeding and replacement feeding - the article explores women's experiences struggling to secure an HIV free baby. At the heart of the findings lie devastating transformations in perceptions of body and self among HIV positive mothers enrolled in the PMTCT programmes, transformations highlighted by the shifting interpretations of mother's milk. The women suffer from extreme fear of feeding their babies HIV infected mother's milk. Very few mothers could afford formula products, and exclusive breastfeeding emerged as the option of the poor 'who have to breastfeed and let their babies die'. From being a prime symbol of nurture and love, mother's milk became a source of death in babies born to HIV positive mothers. The article argues that the incongruity between notions of maternal love and nurture on the one hand, and sexuality, HIV and death on the other, makes the PMTCT programme ill suited as a basis for activism. The material was collected through interviews and discussion with HIV positive mothers and nurse counsellors in Ethiopia and Tanzania, 2004-2006. PMID- 27276402 TI - Antimyeloma activity of bromodomain inhibitors on the human myeloma cell line U266 by downregulation of MYCL. AB - Bromodomain and extraterminal protein (BET) inhibitors suppress the expression of c-MYC. U266, a human myeloma cell line, expresses the MYCL gene, but not the c MYC gene. Our aim was to analyse the antimyeloma activity of BET inhibitors on U266 cells. Two BET inhibitors, I-BET151 and JQ1, were tested. U266 cell proliferation decreased to 61.5 and 54.0% of the control after incubation with 500 nmol/l I-BET151 for 72 and 96 h and to 53.5 and 56.4% of control after incubation with 500 nmol/l JQ1 for 72 and 96 h by MTS tetrazolium, respectively. BET inhibitors induced cell cycle arrest at the G1 phase in U266 cells, but did not induce apoptosis by flow cytometry. According to Gene Set Enrichment Analysis, MYC-related genes were significantly downregulated in U266 cells treated with I-BET151 similar to KMS11 cells that expressed c-MYC. The MYCL1 was expressed in U266 cells, whereas c-MYC and MYCN were not by quantitative real time reverse-transcription-PCR. Incubation with I-BET151 induced downregulation of MYCL1 in U266 cells. BET inhibitors decreased the cell proliferation in U266 cells with overexpression of MYCL less than those without overexpression of MYCL. BET inhibitors induce G1 arrest without apoptosis and interfere with the proliferation of U266 myeloma cells, which express MYCL, but not c-MYC. BET inhibitors might be active in cancers that express MYCL, but not c-MYC. PMID- 27276405 TI - Living and working in spite of antiretroviral therapies: strength in chronicity. AB - This article is a reflection on the relationship between antiretroviral therapies and work. It is concerned with the impact of biomedical protocols and biotechnologies on the 'lifeworlds' of a small group of seropositive men employed in the construction industry in Milan. Construction workers stand out as a category with specific issues because of their physically demanding jobs and are more subject to the potentially damaging physical consequences of antiretroviral therapies, as data suggest. The article is focused on biomedical rationalities and technologies and interrogates the forms of knowledge and the practices that contribute to reshaping seropositive individuals as 'biological and therapeutic citizens'. At the same time, the relationship between identity and health technologies is explored, examining the individual trajectories and strategies displayed by construction workers in order to cultivate their own ideas of personhood and conception of identity. How they rethink their presence within the work environment is shown in light of drug regimens and through a creative manipulation of antiretroviral therapies. PMID- 27276406 TI - Genomics as public health? Community genetics and the challenge of personalised medicine in Cuba. AB - Making use of a comparative perspective on the emergence of 'breast cancer genetics' in the different cultural context of the UK and Cuba, this article examines the tensions between the modern promise of genomics as personalised medicine and a commitment to public health. Focusing primarily on the Cuba context and drawing on ethnographic research as part of a collaborative project working with genetic professionals and publics, the article examines the particular technologies, identities and socialities at stake in an emerging and evolving field of genetic medicine. It highlights how long-standing continuities in the commitment to the equitable provision of public health, particularly as this relates to 'family medicine', are central to understanding the scope and expansion of 'community genetics' interventions, even when at the level of local practice, public health is also now subject to the unequal dynamics of economic necessity through the working out of 'lo informal'. Illuminating the different ways agency, risk, responsibility, citizenship and activism get configured by and between publics and health professionals in Cuba, the article reveals the challenges and opportunities posed by predictive genomic medicine in relation to the dynamic and shifting terrain of public health. PMID- 27276407 TI - Bionetworking: experimental stem cell therapy and patient recruitment in India. AB - Over the last three to four years, an increasing number of private and public sector tertiary level hospitals and research centres in India have been using stem cell therapy, especially adult stem cell therapy, in the guise of experimental therapy for a variety of medical conditions. The promotion and growth of this experimental field across local and national borders traverses regulatory, ethical, social and financial boundaries. In this complex context, the article examines how healthcare centres in India negotiate bio-medical and health care circumstances in promoting a therapy that raises questionable medical, technical and ethical issues. The process of promoting experimental stem cell therapy is explained here by employing the concept of bionetworking and illustrated by two case studies of hospital groups. The case studies show how through bionetworking a centre creates and maintains novel networks of mutual exchanges with other collaborative bodies situated in local, national and global relations of inequality. Drawing on a three-month period of fieldwork and interviews in various locations in India, this article shows that: (1) Questionable stem cell therapy is promoted through bionetworks that resonate across local, national and global constellations; (2) Regulatory gaps facilitate the growth of such therapeutic practices; (3) The experimental stem cell therapies augment the healthcare divide in Indian society; (4) The weakening Indian state facilitates commercialisation of health, indirectly supporting the 'bionetworking' practices of therapy providers. PMID- 27276408 TI - Between religious philanthropy and individualised medicine: situating inherited breast cancer risk in Greece. AB - This article explores cultural articulations of inherited breast cancer risk at the meeting-point between religious philanthropy and individualised medicine. Drawing on the particularities of the ethnographic context of Northern Greece, in a rural area among a population facing the uneven distribution of biotechnologies, this analysis intends to show how developments in the field of breast cancer prevention and genetics are interwoven with the challenges and possibilities of the modernisation and secularisation processes. Notions of 'control' or 'protection' are put to work in medical discourse and the religious domain, through a renewed repertoire of pre-existing meaning-systems that highlight often contrasting aspects of collectivity and individuality. For women with high-risk family history of breast cancer, these tensions are reflected in ways they negotiate articulations of their biology, inherited risk and female subjectivity. In effect, the issues of inequality and religious philanthropy bring forth a different terrain for thinking about the biosocial configurations and the image of individualised consumers that genetic knowledge has been said to enforce or endorse. PMID- 27276409 TI - Rationalisation and racialisation in the Rainbow Nation: inequalities and identity in the South African bone marrow transplant network. AB - This article examines discourses and practises in the professional network of people and organisations in South Africa that comprise the bone marrow/haematopoietic stem cell transplantation (BMT) network. A prominent discursive inter-relationship asserts that some genetically inherited Human Leukocyte Antigen (HLA) types appear in certain ethnic populations more commonly than others, meaning that patients are most likely to find a transplant match with someone in the same ethnic group. The South African BMT network efforts to increase the number of donors from ethnic groups not well represented on the registry are crucial given South Africa's unique and diverse gene pool. This inter-relationship is at the heart of a complex interweaving of genomics, ethnicity, culture, South African nationhood, and the limits of bodily integrity. It necessitates serious engagement in health resource inequalities and burgeoning biosocial identities in a diverse South Africa, especially given its history and its contemporary political agenda of transformation. The analysis of fieldwork is particularly informed by Troy Duster's concept of feedback loops and Paul Rabinow's work on biosociality. Drawing from this analysis, the article also suggests possibilities for policy and practical application. PMID- 27276411 TI - A History of the US Army Nurse Corps by Mary T. Sarnecky (1999). PMID- 27276410 TI - Tests for life chances: CD4 miracles and obstacles in Uganda. AB - This article discusses the relationship between technologies, socialities and inequities based on case material from a recent study about the first generation of people living with ART - Antiretroviral Therapy - in Uganda. The authors discuss how the diagnostic technologies of HIV tests, 'CD4 counts', and weight measuring produce results and numbers that are appropriated by people living with HIV to reflect upon their lives, bodies and relationships and hence influence their socialities and subjectivities. It is argued that because treatment programmes and especially their associated technologies vary greatly in Uganda, the programmes themselves introduce inequity in the already unequal landscape of HIV patients. In debates about biomedical technology and about HIV/AIDS it has been suggested that new kinds of socialities emerge, which have been conceptualised as 'therapeutic citizenship' and 'bio-sociality'. In the study on which the present article is based, clientship, friendship and kinship are kinds of sociality that play a much larger part in informants' lives than do 'therapeutic citizenship' and 'bio-sociality'. The authors attribute these findings, not only to the Ugandan setting, but to the method of doing extended case studies, which were not institution and programme based, but family and home based. PMID- 27276412 TI - Women at the Crossroads: A Prostitute Community's Response to AIDS in Urban Senegal by Michelle Lewis Renaud. PMID- 27276413 TI - Ageing In Today's World: Conversations between an Anthropologist and a Physician by Renee Rose Shield and Stanley M. Aronson. PMID- 27276414 TI - Culture, subject, psyche. Dialogues in psychoanalysis and anthropology, edited by Anthony Molino. PMID- 27276416 TI - Muslim communities of grace, by Jamil M. Abun-Nasr. PMID- 27276415 TI - Narcotic culture. A history of drugs in China, by Frank Dikotter, Lars Laamann and Zhou Xun. PMID- 27276417 TI - A complex delight. The secularization of the breast, 1350-1750, by Margaret R. Miles. PMID- 27276418 TI - Chemoselective Radical Dehalogenation and C-C Bond Formation on Aryl Halide Substrates Using Organic Photoredox Catalysts. AB - Despite the number of methods available for dehalogenation and carbon-carbon bond formation using aryl halides, strategies that provide chemoselectivity for systems bearing multiple carbon-halogen bonds are still needed. Herein, we report the ability to tune the reduction potential of metal-free phenothiazine-based photoredox catalysts and demonstrate the application of these catalysts for chemoselective carbon-halogen bond activation to achieve C-C cross-coupling reactions as well as reductive dehalogenations. This procedure works both for conjugated polyhalides as well as unconjugated substrates. We further illustrate the usefulness of this protocol by intramolecular cyclization of a pyrrole substrate, an advanced building block for a family of natural products known to exhibit biological activity. PMID- 27276419 TI - Beyond the Ebola Battle--Winning the War against Future Epidemics. PMID- 27276420 TI - A statistical method for detecting differentially expressed SNVs based on next generation RNA-seq data. AB - In this article, we propose a new statistical method-MutRSeq-for detecting differentially expressed single nucleotide variants (SNVs) based on RNA-seq data. Specifically, we focus on nonsynonymous mutations and employ a hierarchical likelihood approach to jointly model observed mutation events as well as read count measurements from RNA-seq experiments. We then introduce a likelihood ratio based test statistic, which detects changes not only in overall expression levels, but also in allele-specific expression patterns. In addition, this method can jointly test multiple mutations in one gene/pathway. The simulation studies suggest that the proposed method achieves better power than a few competitors under a range of different settings. In the end, we apply this method to a breast cancer data set and identify genes with nonsynonymous mutations differentially expressed between the triple negative breast cancer tumors and other subtypes of breast cancer tumors. PMID- 27276422 TI - Indirect DNA Sequence Readout by LAGLIDADG Homing Endonucleases. AB - In this issue of Structure, Lambert et al. (2016) describe extensive structural and functional work on meganucleases, the group of homing endonucleases most commonly adapted to genome engineering applications. The data are of interest to structural biologists, evolutionary biologists, protein designers, and genome engineers. PMID- 27276421 TI - Effects of renal impairment on the pharmacokinetics of orally administered deferiprone. AB - AIMS: In light of the growing recognition of renal disease in thalassemia, it is important to understand the impact of renal impairment on the pharmacokinetics of iron chelators. This study evaluated the pharmacokinetics and safety of the iron chelator deferiprone (DFP) in subjects with renal impairment in comparison with healthy volunteers (HVs). METHODS: Thirty-two subjects were categorized into four groups based on degree of renal impairment: none, mild, moderate or severe, as determined by estimated glomerular filtration rate (eGFR). All subjects received a single oral dose of 33 mg kg(-1) DFP, provided serum and urine samples for pharmacokinetic assessment over 24 h and were monitored for safety. RESULTS: Renal clearance of DFP decreased as renal impairment increased. However, based on Cmax , AUC(0,t) and AUC(0,infinity), there were no significant group differences in systemic exposure, because less than 4% of the drug was excreted unchanged in the urine. DFP is extensively metabolized to a renally excreted, pharmacologically inactive metabolite, deferiprone 3-O-glucuronide (DFP-G), which exhibited higher Cmax , AUC(0,t), AUC(0,infinity) and longer tmax and t1/2 in the renally impaired groups compared with HVs. The Cmax and AUCs of DFP-G increased as eGFR decreased. Overall, 75%-95% of the dose was retrieved in urine, either as DFP or DFP-G, regardless of severity of renal impairment. With respect to safety, DFP was well tolerated. CONCLUSIONS: These data suggest that no adjustment of the DFP dosage regimen in patients with renal impairment is necessary, as there were no significant changes in the systemic exposure to the drug. PMID- 27276423 TI - JAK1 Takes a FERM Hold of Type II Cytokine Receptors. AB - Janus kinases (JAKs) initiate the intracellular signaling cascade triggered by exposure of cells to cytokines and interferons. In order to achieve this, JAKs are bound to the intracellular domain of specific cytokine receptors immediately adjacent to the cell membrane. In this issue of Structure, Ferrao et al. (2016) provide structural details of such an interaction and in doing so, identify for the first time the motif used by type II cytokine receptors to recruit JAK1. PMID- 27276424 TI - The Most Interesting Enzyme in the World. AB - Ribonucleotide reductases of the class I family are alpha2beta2 tetramers. Like all RNRs they are subject to allosteric control mechanisms affecting activity and specificity. In this issue of Structure, Johansson et al. (2016) present a structural analysis of an unusual mode of activity site regulation. PMID- 27276425 TI - Time to Stop Holding the Elevator: A New Piece of the Transport Protein Mechanism Puzzle. AB - In this issue of Structure, McCoy et al. (2016) describe the 2.55-A X-ray structure of the outward-facing occluded conformation of the Bacillus cereus maltose transporter MalT. This structure represents the penultimate piece needed to complete the picture of the transport cycle of the glucose superfamily of membrane-spanning EIIC components. PMID- 27276426 TI - Lipopolysaccharide Transport to the Cell Surface: New Insights in Assembly into the Outer Membrane. AB - In this issue of Structure, Botos et al. (2016) report crystal structures of the outer membrane LptDE translocon from three relevant Gram-negative pathogens. This study provides new details into the molecular mechanism of lipopolysaccharide assembly at the cell surface. PMID- 27276428 TI - Production of Heteromeric Transmembrane Receptors with Defined Subunit Stoichiometry. PMID- 27276429 TI - The first outbreak of Taenia ovis infection in China. AB - Infection of Taenia ovis metacestodes in sheep or goats causes great economic losses due to condemnation of carcasses. T. ovis infection is not formally recorded in China to date. In October, 2015, T. ovis infection occurred in Jingtai County, China, and 113 of 192 sheep from one farm were infected. Cysts resided in the cardiac and skeletal muscle, and evaginated metacestodes had four suckers and scolex armed with approximately 23 hooks. Using cox1 and nad1 as molecular markers, the sample was further identified and the results showed that the cox1 and nad1 nucleotide sequences of the sample shared 99% identity with that of T. ovis and 75%-91.3% with those of other Taenia species. Taken together, these results confirm the first occurrence of T. ovis in China. PMID- 27276430 TI - Feeding Disorders in Children With Autism Spectrum Disorders Are Associated With Eosinophilic Esophagitis. AB - OBJECTIVES: Eosinophilic esophagitis (EoE) can present as food selectivity or feeding disorders in children. Children with autism spectrum disorders (ASDs) commonly demonstrate behavioral food selectivity in type and texture, which often leads to the diagnosis of feeding disorder. We sought to evaluate the association of ASD with EoE. METHODS: A retrospective matched case-cohort study was performed using the Military Health System database from October 2008 to September 2013. We performed a 1:5 case-control match by age, sex, and enrollment timeframe. Feeding disorders, EoE, and atopic disorders were defined using diagnostic and procedure codes. RESULTS: There were 45,286 children with ASD and 226,430 matched controls. EoE was more common in children with ASD (0.4%) compared with controls (0.1%). Feeding disorders were associated with EoE in both children with ASD and controls. Feeding disorders also had a higher odds ratio for EoE compared with other atopic conditions, among both children with ASD (7.17, 95% confidence interval [CI] 4.87-10.5) and controls (11.5, 95% CI 7.57-17.5). Compared with controls with a feeding disorder, children with ASD and a feeding disorder had no difference in the rate of diagnosed EoE (0.85, 0.95% CI 0.39-1.88). CONCLUSIONS: Children with ASD are more likely to be diagnosed with EoE compared with controls; however, among children with feeding disorders, there is no difference in the odds of EoE. A diagnosis of feeding disorder was strongly associated with EoE. Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE. PMID- 27276431 TI - Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial. AB - BACKGROUND: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status. OBJECTIVE: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula. METHODS: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined. RESULTS: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA. CONCLUSIONS: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes. PMID- 27276427 TI - The C-Terminal Arm of the Human Papillomavirus Major Capsid Protein Is Immunogenic and Involved in Virus-Host Interaction. AB - Cervical cancer is the second most prevalent malignant tumor among women worldwide. High-risk human papillomaviruses (HPVs) are believed to be the major causative pathogens of mucosal epithelial cancers including cervical cancer. The HPV capsid is made up of 360 copies of major (L1) and 72 copies of minor (L2) capsid proteins. To date, limited high-resolution structural information about the HPV capsid has hindered attempts to understand details concerning the mechanisms by which HPV assembles and infects cells. In this study, we have constructed a pseudo-atomic model of the HPV59 L1-only capsid and demonstrate that the C-terminal arm of L1 participates in virus-host interactions. Moreover, when conjugated to a scaffold protein, keyhole limpet hemocyanin (KLH), this arm is immunogenic in vivo. These results provide new insights that will help elucidate HPV biology, and hence pave a way for the design of next-generation HPV vaccines. PMID- 27276432 TI - Propofol Use in Pediatric Patients With Food Allergy and Eosinophilic Esophagitis. AB - Propofol is a safe, well-tolerated anesthetic that is labeled as contraindicated in patients with egg or soy allergy. This contraindication has become increasingly problematic given the rising incidence of food allergy and eosinophilic esophagitis (EoE). To address this issue, we studied practice patterns of propofol use for esophagogastroduodenoscopies in children with EoE and food allergies at our institution. A retrospective observational study of 1365 esophagogastroduodenoscopies from January 2013 to June 2014 was performed. Data were analyzed using Student t tests, chi square tests, Fisher exact tests, and multivariable logistic regression. We found that propofol was used significantly less in patients with egg or soy allergy, and in patients with EoE, even after adjusting for the presence of food allergy. There was no difference in complication rates relative to propofol use. Propofol was used safely in pediatric patients with EoE and food allergy in this limited single-center review. PMID- 27276434 TI - Sodium Intake Requirements for Preterm Neonates: Review and Recommendations. AB - It is widely accepted that sodium is an essential nutritional electrolyte and its deficiency is associated with neurological sequelae and poor growth. The provision of an adequate sodium intake to preterm neonates is hampered by the technical difficulty in clinically assessing total body sodium content. As addressed in this review, there is a lack of consensus on the definition of hyponatremia early in life, but there is no evidence that it should deviate from the widely accepted normative data for adult subjects. A low urinary sodium content is accepted by many as reflecting total body sodium deficiency, yet spot urinary sodium measurements are of questionable clinical value. The hormonal regulation of sodium homeostasis is here reviewed and the mechanism accounting for sodium deficiency-induced growth impairment in preterm infants addressed. Lastly, we provide evidence-based gestational and postnatal age-dependent recommendations for the provision of adequate sodium intake to preterm neonates. PMID- 27276433 TI - NASPGHAN 2015 Distinguished Service Award. PMID- 27276435 TI - 2015 Harry Shwachman Award. PMID- 27276437 TI - Efficient access to alkynylated quinalizinones via the gold(i)-catalyzed aminoalkynylation of alkynes. AB - The gold-catalyzed aminoalkynylation of alkynes for the synthesis of quinalizinones is reported. For instance, the reaction of pyridinoalkynes with 1 [(triisopropylsilyl)-ethynyl]-1,2-benziodoxol-3(1H)-one (TIPS-EBX) in the presence of a catalytic amount of AuCl at 50 degrees C afforded alkynylated quinalizinones in 57-87% yields. PMID- 27276438 TI - Nitrogen Molecule Adsorption on Cationic Tantalum Clusters and Rhodium Clusters and Desorption from Their Nitride Clusters Studied by Thermal Desorption Spectrometry. AB - Adsorption and desorption of N2 molecules onto cationic Ta and Rh clusters in the gas phase were investigated in the temperature range of 300-1000 K by using thermal desorption spectrometry in combination with density functional theory (DFT) calculations. For Ta6(+), the first N2 molecule was found to adsorb dissociatively, and it remained adsorbed when Ta6(+)N2 was heated to 1000 K. In contrast, the second and the subsequent N2 molecules adsorbed weakly as a molecular form and were released into the gas phase when heated to 600 K. The difference can be explained in terms of the activation barrier between the molecular and dissociative forms. On the other hand, when Ta clusters were generated in the presence of N2 gas by the laser ablation of a Ta rod, isomeric clusters, TanNm(+), having heat resistivity were formed. For Rh6(+), N2 adsorbed molecularly at 300 K and desorbed totally at 450 K. These results were consistent with the DFT calculations, indicating that the dissociative adsorption of N2 is endothermic. PMID- 27276436 TI - Lactulose Breath Test Gas Production in Childhood IBS Is Associated With Intestinal Transit and Bowel Movement Frequency. AB - OBJECTIVES: In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. METHODS: Children (ages 7-17 years) with pediatric Rome III IBS completed validated psychosocial questionnaires and a 2-week daily diary capturing pain and stooling characteristics. Stool form determined IBS subtype. Subjects then completed a 3-hour lactulose breath test for measurement of total breath hydrogen and methane production. Carmine red was used to determine whole intestinal transit time. RESULTS: A total of 87 children (mean age 13 +/- 2.6 [standard deviation] years) were enrolled, of whom 50 (57.5%) were girls. All children produced hydrogen and 51 (58.6%) produced methane. Hydrogen and methane production did not correlate with either abdominal pain frequency/severity or psychosocial distress. Hydrogen and methane production did not differ significantly by IBS subtype. Methane production correlated positively with whole intestinal transit time (r = 0.31, P < 0.005) and inversely with bowel movement frequency (r = -0.245, P < 0.05). Methane production (threshold 3 ppm) as a marker for identifying IBS-C had a sensitivity of 60% and specificity of 42.9%. CONCLUSIONS: Lactulose breath test total methane production may serve as a biomarker of whole intestinal transit time and bowel movement frequency in children with IBS. In children with IBS, lactulose breath test hydrogen and methane production did not, however, correlate with abdominal pain, IBS subtype, or psychosocial distress. PMID- 27276439 TI - Switching the Stiffness of Polyelectrolyte Assembly by Light to Control Behavior of Supported Cells. AB - Polyelectrolyte block copolymer micelles assembled thin film is switched in response to local photocatalytic reactions on titanium dioxide, resulting in a layer of variable height, stiffness in response to visible light irradiation. Preosteoblasts migrate toward stiffer side of the substrates. PMID- 27276440 TI - Car free cities: Pathway to healthy urban living. AB - BACKGROUND: Many cities across the world are beginning to shift their mobility solution away from the private cars and towards more environmentally friendly and citizen-focused means. Hamburg, Oslo, Helsinki, and Madrid have recently announced their plans to become (partly) private car free cities. Other cities like Paris, Milan, Chengdu, Masdar, Dublin, Brussels, Copenhagen, Bogota, and Hyderabad have measures that aim at reducing motorized traffic including implementing car free days, investing in cycling infrastructure and pedestrianization, restricting parking spaces and considerable increases in public transport provision. Such plans and measures are particularly implemented with the declared aim of reducing greenhouse gas emissions. These reductions are also likely to benefit public health. AIMS: We aimed to describe the plans for private car free cities and its likely effects on public health. METHODS: We reviewed the grey and scientific literature on plans for private car free cities, restricted car use, related exposures and health. RESULTS: An increasing number of cities are planning to become (partly) private car free. They mainly focus on the reduction of private car use in city centers. The likely effects of such policies are significant reductions in traffic-related air pollution, noise, and temperature in city centers. For example, up to a 40% reduction in NO2 levels has been reported on car free days. These reductions are likely to lead to a reduction in premature mortality and morbidity. Furthermore the reduction in the number of cars, and therefore a reduction in the need for parking places and road space, provides opportunities to increase green space and green networks in cities, which in turn can lead to many beneficial health effects. All these measures are likely to lead to higher levels of active mobility and physical activity which may improve public health the most and also provide more opportunities for people to interact with each other in public space. Furthermore, such initiatives, if undertaken at a sufficiently large scale can result in positive distal effects and climate change mitigation through CO2 reductions. The potential negative effects which may arise due to motorized traffic detouring around car free zone into their destinations also need further evaluation and the areas in which car free zones are introduced need to be given sufficient attention so as not to become an additional way to exacerbate socioeconomic divides. The extent and magnitude of all the above effects is still unclear and needs further research, including full chain health impact assessment modeling to quantify the potential health benefits of such schemes, and exposure and epidemiological studies to measure any changes when such interventions take place. CONCLUSIONS: The introduction of private car free cities is likely to have direct and indirect health benefits, but the exact magnitude and potential conflicting effects are as yet unclear. This paper has overviewed the expected health impacts, which can be useful to underpin policies to reduce car use in cities. PMID- 27276441 TI - Unveiling the Switching Riddle of Silver Tetracyanoquinodimethane Towards Novel Planar Single-Crystalline Electrochemical Metallization Memories. AB - The switching riddle of AgTCNQ is shown to be caused by the solid electrolyte mechanism. Both factors of bulk phase change and contact issue play key roles in the efficient work of the devices. An effective strategy is developed to locate the formation/disruption of Ag conductive filaments using the planar asymmetric configuration of Au/AgTCNQ/AlOx /Al. These novel electrochemical metallization memories demonstrate many promising properties. PMID- 27276442 TI - Liquid Chromatography Chip with Low-Dispersion and Low-Pressure-Drop Turn Structure Utilizing a Distribution-Controlled Pillar Array. AB - To realize efficient, fast separations on pillar array columns with turns, a novel turn with low-dispersion and low-pressure-drop properties was developed. This "pillar-distribution-controlled" (PDC) turn was designed as a constant radius turn filled with octagonal pillars that were arranged to control the linear velocity of the mobile phase in the radial direction. After the pillar positions were adjusted by computational fluid dynamics analysis, 27 mm long pillar array columns with two turns were fabricated on a 20 * 20 mm(2) silicon glass plate. The PDC turns suppressed the sample dispersion to a similar extent as the previously developed tapered turn, and the pressure drop of the newly designed turn was reduced to ~1/6 that of the tapered turn. Moreover, the C18 modified pillar array column with the PDC turns showed good bioanalytical applicability; five fluorescently labeled amino acids were separated in only 24 s at a linear velocity of 7.5 mm/s. The developed turn structure offers the advantages of longer pillar array columns with more turns for the fast analysis of complex samples. PMID- 27276443 TI - Fibroblast growth factor 21 (FGF21) inhibits macrophage-mediated inflammation by activating Nrf2 and suppressing the NF-kappaB signaling pathway. AB - Our previous report has shown that FGF21 has anti-inflammatory properties in a collagen-induced arthritis (CIA) model. In this study, the underlying molecular mechanisms of action were also investigated using RAW 264.7 cells, a murine monocyte-macrophage. RAW 264.7 cells were pre-incubated with various concentrations (2000, 500, 100ng/ml) of FGF21 and stimulated with LPS to induce oxidative stress and inflammation. The result of flow cytometry showed that beta Klotho, FGF21 specific receptor, was expressed in murine splenic macrophages and RAW 264.7. In vitro, FGF21 reduced the expression of TNF-alpha, IL-1beta, IL-6 and IFN-gamma and increased the level of IL-10 in a dose-dependent manner in LPS stimulated RAW 264.7 macrophages. FGF21 also suppressed profound elevation of ROS production and oxidative stress, as evidenced by an increase of the MDA level and depletion of the intracellular GSH level, and restored the activities of antioxidant enzymes SOD and GSH-Px in LPS-stimulated RAW 264.7 macrophages. Moreover, FGF21 inhibited LPS-induced nuclear factor-kappaB (NF-kappaB) activation, including degradation of I-kappaB and nuclear translocation of p65. In addition, the result of Western blot and real-time PCR showed that FGF21 induced heme oxygenase-1 (HO-1) expression and increased the nuclear transcription factor-E2-related factor 2 (Nrf2) levels in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophages. In conclusion, the results suggest that macrophages are the targets for the anti-inflammatory effects of FGF21, and FGF21 exerted an anti-inflammatory effect mainly via enhancing Nrf2-mediated anti oxidant capacity and suppressing NF-kappaB signaling pathway. PMID- 27276444 TI - Peripartum cardiomyopathy: challenges in diagnosis and management. AB - INTRODUCTION: Peripartum cardiomyopathy (PPCM) is one of the leading causes of maternal mortality all over the world. Fortunately, some of the most important answers to the "PPCM puzzle" are emerging: AREAS COVERED: This is an update that includes current and recent research results. These developments hold promise to importantly decrease mortality from PPCM and increase recovery rates. Expert commentary: Increasing risks for the development and severity of PPCM include a genetic predisposition and the presence of any form of hypertension in pregnancy. Earlier recognition/diagnosis of PPCM confers greater opportunity for full recovery. Important biomarkers have the potential to help to recognize PPCM earlier and to provide better treatment. "Follow the Guidelines" is good advice for the best opportunity to achieve full recovery. These include the use of diuretics, BB, ACEI/ARB in tolerable dosages. Phasing out specific treatments appears to be safe for some; but the process must be individualized. PMID- 27276445 TI - Multi-Ethnic Attitudes Toward Physician-Assisted Death in California and Hawaii. AB - BACKGROUND: As aid-in-dying laws are gaining more public acceptance and support, it is important to understand diverse perceptions toward physician-assisted death (PAD). We compare attitudes of residents from California and Hawaii to identify variables that may predict attitudes toward PAD. METHODS: A cross-sectional online survey of 1095 participants (a 75.8% survey completion rate) from California and 819 from Hawaii (a 78.4% survey completion rate). Data were collected between July through October 2015. RESULTS: Majority of study participants in California (72.5%) and Hawaii (76.5%) were supportive of PAD. Only 36.8% of participants in Hawaii and 34.8% of participants in California reported completing advance directives. To better understand which subgroups were most in favor of PAD, data were analyzed using both recursive partitioning and stepwise logistic regression. Older participants were more supportive of PAD in both states. Also, all ethnic groups were equally supportive of PAD. Completion of advance directives was not a significant predictor of attitudes toward PAD. Persons who reported that faith/religion/spirituality was less important to them were more likely to support PAD in both states. Thus, the major influences on the attitudes to PAD were religious/spiritual views and age, not ethnicity and gender. Even in the subgroups least supportive of PAD, the majority supported PAD. CONCLUSIONS: This study shows that in the ethnically diverse states of California and Hawaii, faith/religion/spirituality and age are major influencers of attitudes toward PAD and not ethnicity and gender. Even in the subgroups least supportive of PAD, the majority supports PAD. PMID- 27276498 TI - INTRAVITREAL TRIAMCINOLONE IN SUSAC SYNDROME. AB - PURPOSE: To report the use of intravitreal triamcinolone for Susac Syndrome in one patient. METHODS: Case report. RESULTS: A 23-year-old woman presented with presented with sudden visual loss in the left eye with associated neurologic symptoms. Ophthalmic examination and fluorescein angiography showed multiple areas of branch retinal artery occlusion, bilaterally. Magnetic resonance imaging showed dot-like, diffusion-restricted lesions in the corpus callosum, and audiometry showed low-frequency sensory hearing loss, compatible with Susac Syndrome. The patient received a single intravitreal injection of triamcinolone (4 mg) in the left eye. One week later, before beginning systemic corticosteroids, all signs and symptoms resolved in the left eye only. CONCLUSION: In cases of delayed systemic corticosteroid therapy, intravitreal triamcinolone resolves the ocular manifestations of Susac Syndrome. PMID- 27276446 TI - Single particle imaging of mRNAs crossing the nuclear pore: Surfing on the edge. AB - Six years ago, the Singer lab published a landmark paper which described how individual mRNA particles cross the nuclear pore complex in mammalian tissue culture cells. This involved the simultaneous imaging of mRNAs, each labeled by a large number of tethered fluorescent proteins and fluorescently tagged nuclear pore components. Now two groups have applied this technique to the budding yeast Saccharomyces cerevisiae. Their results indicate that in the course of nuclear export, mRNAs likely engage complexes that are present on either side of the pore and that these interactions are modulated by proteins present in the messenger ribonucleoprotein (mRNP) complex. These findings lend support to the notion that just before and/or after the completion of nuclear export, mRNPs undergo one or more maturation steps that prepare the packaged mRNAs for translation. These results represent new and exciting insights into the mechanism of mRNA nuclear export. PMID- 27276499 TI - The length of the bridging chain in ansa-metallocenes influences their antiproliferative activity against triple negative breast cancer cells (TNBC). AB - In order to examine whether the length of the bridging chain in ansa-ferrocenes affects their antiproliferative activity against MDA-MB-231 triple negative breast cancer cell lines (TNBC), we synthesized derivatives of the type 1-[bis-(4 hydroxyphenyl)]methylidene-[n]ferrocenophane and 1-[(4-hydroxyphenyl) phenyl]methylidene-[n]ferrocenophane with n = 3, 4, 5. We found that the derivatives of [3]ferrocenophane, the compounds with the shortest bridging chains, are the most active. IC50 values were 0.09 +/- 0.01, 2.41 +/- 0.10, and 1.85 +/- 0.25 MUM for the dihydroxyphenyl derivatives, with n = 3, 4, 5, respectively. These differences can be explained in terms of modification of the key metabolites (radical versus quinone methides) within the ansa series depending on the length of the bridging chain. The derivative of [5]ferrocenophane, possessing two -[bis-(4-hydroxyphenyl)]methylidene groups, was also prepared. Surprisingly, this relatively large molecule is also active (IC50 = 2.7 +/- 0.3 MUM). Two ruthenocenophane analogs were also synthesized. These ruthenium compounds are practically inactive against MDA-MB-231 cells. The unusual chemistry of these different compounds is discussed in terms of elucidating the mechanism underlying their diverse antiproliferative activity, and their specific advantages are evaluated. PMID- 27276500 TI - Core-Shell Microgels with Switchable Elasticity at Constant Interfacial Interaction. AB - Hydrogels based on poly(N-isopropylacrylamide) (pNIPAAm) exhibit a thermo reversible volume phase transition from swollen to deswollen states. This change of the hydrogel volume is accompanied by changes of the hydrogel elastic and Young's moduli and of the hydrogel interfacial interactions. To decouple these parameters from one another, we present a class of submillimeter sized hydrogel particles that consist of a thermosensitive pNIPAAm core wrapped by a nonthermosensitive polyacrylamide (pAAm) shell, each templated by droplet-based microfluidics. When the microgel core deswells upon increase of the temperature to above 34 degrees C, the shell is stretched and dragged to follow this deswelling into the microgel interior, resulting in an increase of the microgel surficial Young's modulus. However, as the surface interactions of the pAAm shell are independent of temperature at around 34 degrees C, they do not considerably change during the pNIPAAm-core volume phase transition. This feature makes these core-shell microgels a promising platform to be used as building blocks to assemble soft materials with rationally and independently tunable mechanics. PMID- 27276501 TI - Catalysis of Cascade and Multicomponent Reactions of Carbonyl Compounds and C?H Acids by Electricity. AB - This review is concerned with modern trends in the use of electrochemically induced chain reactions in cascade and multicomponent electroorganic synthesis. The review summarizes the data on the use of electrochemically induced chain reactions in cascade and multicomponent organic synthesis, which were published mainly in the last decade. PMID- 27276502 TI - Neutron Scattering of Residual Hydrogen in 1,4-Dioxane-d8 Liquid: Understanding Measurements with Molecular Dynamics Simulations. AB - That incoherent scattering from protiated molecular liquids adds a constant background to the measured scattering intensity is well-known, but less appreciated is the fact that coherent scattering is also induced by the presence of hydrogen in a deuterated liquid. In fact, the scattering intensity can be very sensitive, in the small-q region, with respect to the amounts and distribution of residual H in the system. We used 1,4-dioxane liquid to demonstrate that the partial structure factors of the HD and DD atom pairs contribute significantly to intermolecular scattering and that uncertainty in the extent of deuteration account for discrepancies between simulations and measurements. Both contributions to uncertainty have similar magnitudes: scattering interference of the hydrogen-deuterium pair, and complementary interference from the deuterium deuterium pair by virtue of chemical inhomogeneity. This situation arises in practice since deuteration of liquids is often 99% or less. A combined experimental and extensive computational study of static thermal neutron scattering of 1,4-dioxane demonstrates the foregoing. We show, through simulations, that the reason for the differences is the content of protiated dioxane (vendors quote 1%). We estimate that up to 5% (at 298 K and at 343 K) protiated molar fraction may be involved in generating the scattering differences. Finally, we find that the particular distribution of hydrogen in the protiated molecules affects the results significantly; here, we considered molecules to be either fully protiated or fully deuterated. This scenario best reconciles the computational and experimental results, and leads us to speculate that the deuteration synthesis process tends to leave a molecule either fully deuterated or fully protiated. Although we have used 1,4-dioxane as a model liquid, the effects described in this study extend to similar liquids, and similar systematic experimental/computational studies can be performed to either understand measurements or calibrate/validate molecular dynamics models. PMID- 27276503 TI - Building Evidence: Fuze Versus Skype for Dance-Based Therapy With Older Adults and Nursing Students. PMID- 27276504 TI - Toward a Central Repository for Sharing Nursing Informatics' Best Practices. PMID- 27276505 TI - Teaching Electronic Health Record Communication. PMID- 27276506 TI - An Alternative Narrative. PMID- 27276508 TI - Chlorine Insertion Promoting Iron Reduction in Ba-Fe Hexagonal Perovskites: Effect on the Structural and Magnetic Properties. AB - BaFeCl0.13(2)O2.48(2) has been synthesized and studied. A proper tuning of the synthetic route has been designed to stabilize this compound as a single phase. The thermal stability and evolution, along with the magnetic and structural properties are reported here. The crystal structure has been refined from neutron powder diffraction data, and it is of the type (hhchc)2-10H. It is stable up to a temperature of 900 degrees C, where the composition reads BaFeCl0.13(2)O2.34(2). The study by electron microscopy shows that the crystal structure suffers no changes in the whole BaFeCl0.13(1)O3-y (2.34 <= 3 - y <= 2.48) compositional range. Refinement of the magnetic structure shows that the Fe is antiferromagneticaly ordered, with the magnetic moment parallel to the ab plane of the hexagonal structure. At higher temperature, a nonreversible phase transition into a (hchc)-4H structure type takes place with overall composition BaFeCl0.13(1)O2.26(1). Microstructural characterization shows that, in some crystals, this phase intergrows with a seemingly cubic related phase. Differences between these two crystalline phases reside in the chlorine content, which keeps constant through the phase transition for the former and disappears for the latter. PMID- 27276507 TI - Eruptive Melanocytic Naevi Caused by Radotinib Therapy in Patients with Chronic Myeloid Leukaemia: 10 cases and a literature Review. PMID- 27276509 TI - Crystallographic and Dynamic Aspects of Solid-State NMR Calibration Compounds: Towards ab Initio NMR Crystallography. AB - The excellent results of dispersion-corrected density functional theory (DFT-D) calculations for static systems have been well established over the past decade. The introduction of dynamics into DFT-D calculations is a target, especially for the field of molecular NMR crystallography. Four (13) C ss-NMR calibration compounds are investigated by single-crystal X-ray diffraction, molecular dynamics and DFT-D calculations. The crystal structure of 3-methylglutaric acid is reported. The rotator phases of adamantane and hexamethylbenzene at room temperature are successfully reproduced in the molecular dynamics simulations. The calculated (13) C chemical shifts of these compounds are in excellent agreement with experiment, with a root-mean-square deviation of 2.0 ppm. It is confirmed that a combination of classical molecular dynamics and DFT-D chemical shift calculation improves the accuracy of calculated chemical shifts. PMID- 27276510 TI - Borderline Resectable Pancreatic Cancer: Answering the Most Important Question First. PMID- 27276512 TI - A strain-tunable nanoimprint lithography for linear variable photonic crystal filters. AB - This paper presents the fabrication methodology of a linear variable photonic crystal (PC) filter with narrowband reflection that varies over a broad spectral range along the length of the filter. The key component of the linear variable PC filter is a polymer surface-relief grating whose period changes linearly as a function of its position on the filter. The grating is fabricated using a nanoreplica molding process with a wedge-shaped elastomer mold. The top surface of the mold carries the grating pattern and the wedge is formed by a shallow angle between the top and bottom surfaces of the mold. During the replica molding process, a uniaxial force is applied to stretch the mold, resulting in a nearly linearly varying grating period. The period of the grating is determined using the magnitude of the force and the local thickness of the mold. The grating period of the fabricated device spans a range of 421.8-463.3 nm over a distance of 20 mm. A high refractive index dielectric film is deposited on the graded period grating to act as the waveguide layer of the PC device. The resonance reflection feature of the device varies linearly in a range of 680.2-737.0 nm over the length of the grating. PMID- 27276511 TI - Metformin and resveratrol inhibit Drp1-mediated mitochondrial fission and prevent ER stress-associated NLRP3 inflammasome activation in the adipose tissue of diabetic mice. AB - OBJECTIVE: This study was designed to investigate the hypothesis that metformin and resveratrol exhibited the same effect on inhibition of NLRP3 inflammasome activation with regulation of AMPK in adipose tissue exposed to high glucose. METHODS: To induce adipose tissue dysfunction, we treated epididymal adipose tissue of mice or differentiated 3T3-L1 adipocytes with high glucose (33 mM) for 24 h. Meanwhile, mice were injected with streptozotocin STZ to induce diabetes and followed by oral administration of metformin (200 mg/kg), resveratrol (50 mg/kg) or ER stress inhibitor TUDCA (50 mg/kg) for 7 days. The effects of metformin and resveratrol on ROS production, mitochondrial fission, ER stress, TXNIP/NLRP3 inflammasome activation, inflammation and apoptosis were observed. RESULTS: Metformin and resveratrol inhibited ROS-associated mitochondrial fission by upregulating Drp1 phosphorylation (Ser 637) in an AMPK-dependent manner, and then suppressed ER stress indicated by dephosphorylation of IRE1alpha and eIF2alpha in the adipose tissue. As a result from suppressing TXNIP/NLRP3 inflammasome activation, metformin and resveratrol inhibited inflammation and reduced cell apoptosis in adipose tissue or adipocytes exposed to high glucose. CONCLUSION: Metformin and resveratrol protected mitochondrial integrity by inhibiting Drp1 activity and prevented NLRP3 inflammasome activation by suppressing ER stress, and thereby protected adipose function from high glucose insult. PMID- 27276513 TI - Endoscopic approaches to pancreatic disease. AB - PURPOSE OF REVIEW: Endoscopy plays a central role in the evaluation and management of patients with pancreatic disease. This review focuses on recent clinically relevant developments and timely research questions related to endoscopy in acute and chronic pancreatitis. RECENT FINDINGS: Endoscopic ultrasound (EUS) has moved to the forefront of the evaluation of unexplained pancreatitis; endoscopic retrograde cholangiopancreatography (ERCP) for recurrent acute pancreatitis remains controversial but commonly practiced; fully covered metallic stents are challenging traditional stent therapy in the treatment of benign biliary and pancreatic strictures due to chronic pancreatitis; endoscopic drainage has become central in the therapeutic algorithm for pancreatic fluid collections; EUS-guided access to the pancreatic duct in cases of unsuccessful ERCP is a promising new platform that requires additional research and development. The evidence in these areas is discussed, with an emphasis on recent high-impact publications. SUMMARY: There have been significant recent advances in our endoscopic approach to pancreatic disease; however, additional research is necessary toward providing high-quality, evidence-based care in this area. PMID- 27276515 TI - Erratum. AB - [This corrects the article DOI: 10.1590/bjpt-rbf.2014.0101]. PMID- 27276514 TI - [Local History]. PMID- 27276516 TI - Successful use of eltrombopag for surgical preparation in a patient with ANKRD26 related thrombocytopenia. PMID- 27276517 TI - Configuring Electronic States in an Atomically Precise Array of Quantum Boxes. AB - A 2D array of electronically coupled quantum boxes is fabricated by means of on surface self-assembly assuring ultimate precision of each box. The quantum states embedded in the boxes are configured by adsorbates, whose occupancy is controlled with atomic precision. The electronic interbox coupling can be maintained or significantly reduced by proper arrangement of empty and filled boxes. PMID- 27276518 TI - Quantitative Targeted Absolute Proteomics of Transporters and Pharmacoproteomics Based Reconstruction of P-Glycoprotein Function in Mouse Small Intestine. AB - The purpose of this study was to investigate whether a pharmacokinetic model integrating in vitro mdr1a efflux activity (which we previously reported) with in vitro/in vivo differences in protein expression level can reconstruct intestinal mdr1a function. In situ intestinal permeability-surface area product ratio between wild-type and mdr1a/1b (-/-) mice is one of the parameters used to describe intestinal mdr1a function. The reconstructed ratios of six mdr1a substrates (dexamethasone, digoxin, loperamide, quinidine, verapamil, vinblastine) and one nonsubstrate (diazepam) were consistent with the observed values reported by Adachi et al. within 2.1-fold difference. Thus, intestinal mdr1a function can be reconstructed by our pharmacoproteomic modeling approach. Furthermore, we evaluated regional differences in protein expression levels of mouse intestinal transporters. Sixteen (mdr1a, mrp4, bcrp, abcg5, abcg8, glut1, 4f2hc, sglt1, lat2, pept1, mct1, slc22a18, ostbeta, villin1, Na(+)/K(+)-ATPase, gamma-gtp) out of 46 target molecules were detected by employing our established quantitative targeted absolute proteomics technique. The protein expression amounts of mdr1a and bcrp increased progressively from duodenum to ileum. Sglt1, lat2, and 4f2hc were highly expressed in jejunum and ileum. Mct1 and ostbeta were highly expressed in ileum. The quantitative expression profiles established here should be helpful to understand and predict intestinal transporter functions. PMID- 27276519 TI - Design, Synthesis, and Biological Evaluation of Ganglioside Hp-s1 Analogues Varying at Glucosyl Moiety. AB - Ganglioside Hp-s1 is isolated from the ovary of sea urchin Diadema setosum. It exhibited better neuritogenic activity than GM1 in pheochromocytoma 12 cells. To explore the roles of glucosyl moiety of Hp-s1 in contributing to the neurogenic activity, we developed feasible procedures for synthesis of Hp-s1 analogues (2a 2f). The glucosyl moiety of Hp-s1 was replaced with alpha-glucose, alpha galactose, beta-galactose, alpha-mannose, and beta-mannose, and their biological activities on SH-SY5Y cells and natural killer T (NKT) cells were evaluated. We found that the orientation of C-2 hydroxyl group at glucosyl moiety of Hp-s1 plays an important role to induce neurite outgrowth of SH-SY5Y cells. Surprisingly, compound 2d could activate NKT cells to produce interleukin 2, although it did not show great activity on neurite outgrowth of SH-SY5Y cells. In general, the Hp-s1 might be considered as a lead compound for the development of novel drugs aimed at modulating the activity of neuronal cells. PMID- 27276520 TI - Neonatal Outcomes in Women With Untreated Antenatal Depression Compared With Women Without Depression: A Systematic Review and Meta-analysis. AB - IMPORTANCE: Despite the prevalence of antenatal depression and the fact that only one-third of pregnant women with depression consider it acceptable to take antidepressants, the effect of untreated depression on neonatal outcomes remains to be addressed thoroughly. OBJECTIVE: To undertake a systematic review and meta analysis to understand the effect of untreated depression on neonatal outcomes. DATA SOURCES: We executed our search strategy, with emphasis on its exhaustiveness, in MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials, and Web of Science. The search was conducted in July, 2015. STUDY SELECTION: We included randomized and nonrandomized studies that examined neonatal outcomes in women with depression receiving neither pharmacological nor nonpharmacological treatment compared with women without depression. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles and abstracts, assessed full-text articles, extracted data, and assessed their quality using a modified version of the Newcastle-Ottawa Scale. We pooled data using random-effects meta-analyses, quantified heterogeneity using the I2 statistic, and explored it with subgroup analyses by type of assessment of depression, severity, reported conflicts of interest, and study quality. MAIN OUTCOMES AND MEASURES: Primary outcomes were preterm birth before 37 weeks and before 32 weeks, small and large for gestational age, low birth weight, and neonatal intensive care unit admission. RESULTS: Of the 6646 titles initially identified, 23 studies met inclusion criteria, all observational, with a total of 25 663 women. Untreated depression was associated with significantly increased risks of preterm birth (odds ratio [OR], 1.56; 95% CI, 1.25-1.94; 14 studies; I2, 39%) and low birth weight (OR, 1.96; 95% CI, 1.24-3.10; 8 studies; I2, 48%), with a trend toward higher risks for exposure to more severe depression. While the odds of preterm birth more than doubled in studies reporting conflicts of interest (OR, 2.50; 95% CI, 1.70-3.67; 5 studies; I2, 0%), studies not reporting such conflicts showed more moderate results (OR, 1.34; 95% CI, 1.08-1.66; 9 studies; I2, 30%). CONCLUSIONS AND RELEVANCE: Our results contrast with what is, to our knowledge, the only previous systematic review that examined the question of untreated depression because we found significant risks of 2 key perinatal outcomes, preterm birth and low birth weight. These are important results for pregnant women and clinicians to take into account in the decision-making process around depression treatment. PMID- 27276522 TI - Photoredox-Catalyzed Three-Component Tandem Process: An Assembly of Complex Trifluoromethylated Phthalans and Isoindolines. AB - A novel photoredox-mediated tandem three-component process afforded a wide variety of CF3-containing phthalans and isoindolines in respectable yields and with moderate to excellent diastereoselectivity. PMID- 27276521 TI - Temporal Modulation of Stem Cell Activity Using Magnetoactive Hydrogels. AB - Cell activity is coordinated by dynamic interactions with the extracellular matrix, often through stimuli-mediated spatiotemporal stiffening and softening. Dynamic changes in mechanics occur in vivo through enzymatic or chemical means, processes which are challenging to reconstruct in cell culture materials. Here a magnetoactive hydrogel material formed by embedding magnetic particles in a hydrogel matrix is presented whereby elasticity can be modulated reversibly by attenuation of a magnetic field. Orders of magnitude change in elasticity using low magnetic fields are shown and reversibility of stiffening with simple permanent magnets is demonstrated. The broad applicability of this technique is demonstrated with two therapeutically relevant bioactivities in mesenchymal stem cells: secretion of proangiogenic molecules, and dynamic control of osteogenesis. The ability to reversibly stiffen cell culture materials across the full spectrum of soft tissue mechanics, using simple materials and commercially available permanent magnets, makes this approach viable for a broad range of laboratory environments. PMID- 27276523 TI - The Social Work Role in Reducing 30-Day Readmissions: The Effectiveness of the Bridge Model of Transitional Care. AB - The hospital experience is taxing and confusing for patients and their families, particularly those with limited economic and social resources. This complexity often leads to disengagement, poor adherence to the plan of care, and high readmission rates. Novel approaches to addressing the complexities of transitional care are emerging as possible solutions. The Bridge Model is a person-centered, social work-led, interdisciplinary transitional care intervention that helps older adults safely transition from the hospital back to their homes and communities. The Bridge Model combines 3 key components-care coordination, case management, and patient engagement-which provide a seamless transition during this stressful time and improve the overall quality of transitional care for older adults, including reducing hospital readmissions. The post Affordable Care Act (ACA) and managed care environment's emphasis on value and quality support further development and expansion of transitional care strategies, such as the Bridge Model, which offer promising avenues to fulfil the triple aim by improving the quality of individual patient care while also impacting population health and controlling per capita costs. PMID- 27276524 TI - Gold-Catalyzed Oxidation/C-H Functionalization of Ynones: Efficient and Rapid Access to Functionalized Polycyclic Salicyl Ketones. AB - An efficient strategy to construct salicyl ketones through gold-catalyzed oxidation/C-H functionalization of ynones is reported. A variety of functionalized salicyl ketones are readily accessed by utilizing this non-diazo approach, thus providing a viable alternative to synthetically useful salicyl ketones with a yield up to 98 %. The alpha-oxo gold carbenes generated in situ through gold-catalyzed oxidation of ynones can be trapped effectively by internal aryl and heteroaromatic groups. Electronic and steric effects were also investigated in this reaction. The anticancer activity of one salicyl ketone analogue was investigated and its cytotoxicity assays against the PC-3 prostate cancer cell line and SKOV-3 human ovarian carcinoma cell line yield IC50 were 0.81+/-0.05 and 0.87+/-0.15 MUm, respectively, demonstrating that salicyl ketone analogues showed good anticancer activity. PMID- 27276525 TI - Thermodynamics of Trapping Gases for Underwater Superhydrophobicity. AB - Rough surfaces submerged in a liquid can remain almost dry if the liquid does not fully wet the roughness, and gases are sustained in roughness grooves. Such partially dry surfaces can help reduce drag, enhance boiling, and reduce biofouling. Gases sustained in roughness grooves would be composed of air and the vapor phase of the liquid itself. In this work, the thermodynamics of sustaining gases (e.g., air) is considered. Governing equations are presented along with a solution methodology to determine a critical condition to sustain gases. The critical roughness scale to sustain gases is estimated for different degrees of saturation of gases dissolved in the liquid. It is shown that roughness spacings of less than a micron are essential to sustain gases on surfaces submerged in water at atmospheric pressure. This is consistent with prior empirical data. PMID- 27276527 TI - Comparison of adverse perinatal outcomes after single-needle and double-needle CVS techniques. AB - OBJECTIVE: To determine the impact of the chorion villus sampling (CVS) technique on adverse perinatal outcomes. METHODS: In this case-control study, 412 women who underwent CVS at 11-14 weeks of gestation and 231 women who did not undergo any invasive procedure were retrospectively evaluated. The women in the CVS group were further divided into two groups according to the use of single-needle technique (n=148) vs. double-needle technique (n=264). The adverse outcomes were compared between controls and the two CVS groups, and regression analysis was used to determine the significance of independent contribution. RESULTS: The rate of preeclampsia for the control group was 2.2%, for the double-needle group was 3% and for the single-needle group was 8.1%. CVS with single-needle technique was found to be an independent and statistically significant risk factor for preeclampsia [odds ratio (OR)=2.1, 95% confidence interval (CI); 1.4-2.7, P=0.008]. CONCLUSION: The risk of preeclampsia after CVS appears to be increased with single-needle technique compared with double-needle technique. PMID- 27276526 TI - Striatum on the anxiety map: Small detours into adolescence. AB - Adolescence is the most sensitive period for the development of pathological anxiety. Moreover, specific neural changes associated with the striatum might be related to adolescent vulnerability to anxiety. Up to now, the study of anxiety has primarily focused on the amygdala, bed nucleus of the stria terminalis (BNST), hippocampus and ventromedial prefrontal cortex (vmPFC), while the striatum has typically not been considered as part of the anxiety system. This review proposes the addition of the striatum, a complex, multi-component structure, to the anxiety network by underscoring two lines of research. First, the co-occurrence of the adolescent striatal development with the peak vulnerability of adolescents to anxiety disorders might potentially reflect a causal relationship. Second, the recognition of the role of the striatum in fundamental behavioral processes that do affect anxiety supports the putative importance of the striatum in anxiety. These behavioral processes include (1) attention, (2) conditioning/prediction error, and (3) motivation. This review proposes a simplistic schematic representation of the anxiety circuitry that includes the striatum, and aims to promote further work in this direction, as the role of the striatum in shaping an anxiety phenotype during adolescence could have critical implications for understanding and preventing the peak onset of anxiety disorders during this period. This article is part of a Special Issue entitled SI: Adolescent plasticity. PMID- 27276528 TI - Incretin-based therapy for type 2 diabetes mellitus is promising for treating neurodegenerative diseases. AB - Incretin hormones include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Due to their promising action on insulinotropic secretion and improving insulin resistance (IR), incretin-based therapies have become a new class of antidiabetic agents for the treatment of type 2 diabetes mellitus (T2DM). Recently, the links between neurodegenerative diseases and T2DM have been identified in a number of studies, which suggested that shared mechanisms, such as insulin dysregulation or IR, may underlie these conditions. Therefore, the effects of incretins in neurodegenerative diseases have been extensively investigated. Protease-resistant long-lasting GLP-1 mimetics such as lixisenatide, liraglutide, and exenatide not only have demonstrated promising effects for treating neurodegenerative diseases in preclinical studies but also have shown first positive results in Alzheimer's disease (AD) and Parkinson's disease (PD) patients in clinical trials. Furthermore, the effects of other related incretin-based therapies such as GIP agonists, dipeptidyl peptidase-IV (DPP-IV) inhibitors, oxyntomodulin (OXM), dual GLP-1/GIP, and triple GLP 1/GIP/glucagon receptor agonists on neurodegenerative diseases have been tested in preclinical studies. Incretin-based therapies are a promising approach for treating neurodegenerative diseases. PMID- 27276530 TI - Plasminogen activator inhibitor-1 as a marker of cardiovascular response in professional mountain ultra-marathon runners. PMID- 27276529 TI - Hepatitis B virus surface protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways. AB - The protein inhibitor of activated STAT1 (PIAS1) plays important roles in regulating virus-induced chronic hepatitis, but the interaction between hepatitis B virus (HBV) and hPIAS1 is not clear. Our aim was to verify if HBV encoding proteins enhance the transcription of hPIAS1 and which cis-elements and transcription factors were involved in the mechanism. In order to do, so a series of molecular biological methods, along with functional and histological studies, were performed. We found that the HBV surface protein (HBs) enhanced hPIAS1 transcription through the activities of TAL1, E47, myogenin (MYOG), and NFI, dependent on the activation of p38MAPK and ERK signaling pathways in vitro, which might contribute to the ineffectiveness of treatment in CHB patients. Furthermore, liver samples from patients with high HBsAg levels and HBV DNA displayed increased hPIAS1 expression and high levels of TAL1, E47, MYOG, and NFI, compared to those patients with low HBsAg levels and HBV DNA, and healthy controls. These findings suggest that the HBs protein-induced hPIAS1 transcription requires TAL1, E47, MYOG, NFI, and MAPK signal pathways. It provides new potential targets for antiviral therapeutic strategies for controlling HBV-associated diseases. PMID- 27276531 TI - Potentials of Mangifera indica in the treatment of depressive-anxiety disorders: possible mechanisms of action. AB - BACKGROUND: Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice. METHODS: HeMI (12.5-100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM). RESULTS: HeMI (12.5-100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, p<0.001], [F(6,56)=7.55, p<0.001] in the FST and TST, respectively. Moreover, co-administration of sub therapeutic doses of imipramine or fluoxetine with HeMI (3.125 mg/kg) elicited significant reduction in time spent immobile in the FST. However, pretreatment of mice with parachlorophenylalanine, metergoline, yohimbine or sulpiride abolished the antidepressant-like effect elicited by HeMI. In the EPM, HeMI produced significant [F(5,42)=8.91, p<0.001] increase in open arms exploration by 75.55 % and this effect was blocked by pretreatment of mice with flumazenil or metergoline. CONCLUSIONS: Findings from this study showed antidepressant-like effect of M. indica through interaction with 5-HT2 receptor, alpha2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness. PMID- 27276532 TI - Technique for CT Fluoroscopy-Guided Lumbar Medial Branch Blocks and Radiofrequency Ablation. AB - OBJECTIVE: The purpose of this study is to describe the procedure for CT fluoroscopy-guided lumbar medial branch blocks and facet radiofrequency ablation. CONCLUSION: CT fluoroscopic guidance allows more-precise needle tip positioning and is an alternative method for performing medial branch blocks and facet radiofrequency ablation. PMID- 27276533 TI - A Cu(II)2 Paramagnetic Chemical Exchange Saturation Transfer Contrast Agent Enabled by Magnetic Exchange Coupling. AB - The ability of magnetic exchange coupling to enable observation of paramagnetic chemical exchange saturation transfer (PARACEST) in transition metal ions with long electronic relaxation times (taus) is demonstrated. Metalation of the dinucleating, tetra(carboxamide) ligand HL with Cu(2+) in the presence of pyrophosphate (P2O7)(4-) affords the complex [LCu(II)2(P2O7)](-). Solution-phase variable-temperature magnetic susceptibility data reveal weak ferromagnetic superexchange coupling between the two S = 1/2 Cu(II) centers, with a coupling constant of J = +2.69(5) cm(-1), to give an S = 1 ground state. This coupling results in a sharpened NMR line width relative to a GaCu analogue, indicative of a shortening of taus. Presaturation of the amide protons in the Cu2 complex at 37 degrees C leads to a 14% intensity decrease in the bulk water (1)H NMR signal through the CEST effect. Conversely, no CEST effect is observed in the GaCu complex. These results provide the first example of a Cu-based PARACEST magnetic resonance contrast agent and demonstrate the potential to expand the metal ion toolbox for PARACEST agents through introduction of magnetic exchange coupling. PMID- 27276534 TI - Short Self-Assembling Peptides Are Able to Bind to Copper and Activate Oxygen. AB - We have shown that de novo designed peptides self-assemble in the presence of copper to create supramolecular assemblies capable of carrying out the oxidation of dimethoxyphenol in the presence of dioxygen. Formation of the supramolecular assembly, which is akin to a protein fold, is critical for productive catalysis since peptides possessing the same functional groups but lacking the ability to self-assemble do not catalyze substrate oxidation. The ease with which we have discovered robust and productive oxygen activation catalysts suggests that these prion-like assemblies might have served as intermediates in the evolution of enzymatic function and opens the path for the development of new catalyst nanomaterials. PMID- 27276535 TI - Description and Preliminary Evaluation of a Curriculum for Teaching Conversational Skills to Children With High-Functioning Autism and Other Social Cognition Challenges. AB - PURPOSE: The purpose of this clinical focus article is to provide (a) a detailed description of a school-based intervention designed to teach children with high functioning autism spectrum disorders (HF-ASDs) and other social cognition challenges both the how and the why of conversation and (b) a preliminary evaluation of program outcomes. METHOD: This pilot study involved (a) qualitative and quantitative analysis of video footage of participants' conversational skills at baseline, during intervention, and postintervention; (b) interviews with participants' speech-language pathologist (third author) about individual participant progress; and (c) interviews with instructors responsible for implementing the curriculum regarding overall program effectiveness. Participants were four elementary-aged children with HF-ASDs and other social cognition challenges with deficits in expressive language and auditory processing and comprehension. RESULTS: Analyses of video-recorded footage indicated increases for all four participants in terms of peer-directed interactions, questions asked, use of wh-words to introduce new topics and/or extend conversation on existing topics, and attempts at conversational repair. Three participants also demonstrated increased use of attention-gaining behaviors. Qualitative analysis of transcripts, as well as in-depth interviews with the participants' speech language pathologist and other program instructors, supported these findings. CONCLUSIONS: Preliminary findings from this pilot study suggest that providing comprehensive instruction in many of the basic components required for successful conversation, including explanations for why these components are necessary, may be a promising means of teaching children with HF-ASDs and other social cognition challenges to engage in successful peer-to-peer conversation. PMID- 27276536 TI - [Not Available]. PMID- 27276537 TI - [Perspectives and challenges of the "new" National Health Promotion Policy: to which political arena does management point?]. AB - The "new" National Health Promotion Policy opens up prospects and challenges for the political arena. This is the space where agreements and disagreements relating to decision-making, which will underpin its implementation, are established. This study sought to understand these questions, seeking to reflect upon the formation of arenas, in order to contribute with strategies coherent with the policy. It is a qualitative study, based on the theory of justification and its 'polities' according to Boltanski and Thevenot. Those interviewed were social actors involved with management of this policy. The analysis verified the presence of the polities such as: civic -vision and concepts; project -execution; and industrial - imposed limits. These polities define the arenas where the designated prospects and challenges appear. The configurations arising from the intersection points of these polities reveal arenas established through interests and issues resulting from agreements. It further highlights the grandeur of polities that may be found in controversies or conflicts, especially among the subcategories present in more than one polity. Critical awareness and the establishment of a clear political game are required of the social actors involved in promoting agreements and/or disagreements related to the new policy. PMID- 27276538 TI - [Evaluation of the National Health Promotion Policy (PNPS): prospects and challenges]. AB - This article analyzes prospects and challenges for the evaluation of the implementation of the National Health Promotion Policy in Brazil. Based on a critical review of the literature, it highlights the limits of the approaches that pay little heed to the theory of programs and reject evaluation as know-how entrenched in the historical, cultural and political dynamics of each society. The conclusion is that despite recent advances in this debate, the evaluation of complex, participatory and intersectoral programs imposes in-depth reflection on the nature of proof of effectiveness as well as methodological strategies capable of illuminating aspects of the concept and design of actions and the process of implementation in the local context, over and above the emphasis on risk factors and final results. PMID- 27276539 TI - [Not Available]. PMID- 27276541 TI - [Sustainability of an innovative school food program: a case study in the northeast of Brazil]. AB - The Brazilian School Food Program (PNAE) is intersectoral innature. It encourages social participation and local economies and is considered here as a health promotionpractice. In the Northeastern State of Pernambuco, the city of Tabira acquired international renownin 2012 for the management of its school food program (PAE). This study analyzed the positive and negative factors related to the sustainability of the innovations in Tabira to understand the processes related to the continuity of the innovative actions implemented. The research used a qualitative approach with a case study strategy. A focus group, semi structured interviews with key actors and document analysis were performed. The data were processed using content analysis and the techniques of thematic analysis. Positive organizational and socio-political factors were: the program institutionalization, the efficient use of financial resources, municipalized management, high community participation and the use of local resources. Negative factors were: weak inter-sectoral coordination and training and poor professional qualification. The strong political engagement at the local level showed both positive and negative impacts on sustainability. PMID- 27276540 TI - [The Health Academy Program as a strategy to promote health and healthy lifestyles: the national implementation scenario]. AB - The National Health Promotion Policy reasserted the Brazilian Ministry of Health's commitment to bolster the promotion of health in the Unified Health System. In this context, the Health Academy Program constitutes a new tool of the health network for the enhancement of individual and collective primary healthcare. The scope of this study is to present the program implementation scenario, describing characteristics of its operation in the country. Data were collected through an electronic form sent to all Municipal Health Departments that received federal resources to implement the program. The response rate was 85%, corresponding to 2,418 municipalities. A total of 856 centers were found to be in operation, primarily promoting physical exercise, healthy eating and health education. The main participants were adults and the elderly. Difficulties reported by the administrators involve the inclusion of children and adolescents and the hiring of professionals. Over 90% of the program centers do not depend exclusively on federal funding for operation and receive municipal support to conduct their activities. The results show the potential of the program as a strategy to promote healthcare in the community nationwide in Brazil. PMID- 27276542 TI - [Health promotion policy and urban planning: joint efforts for the development of healthy cities]. AB - The National Health Promotion Policy (PNPS) defines strategies for devising inter sectoral public policies that ensure the development of healthy cities. Urban planning constitutes a tool to improve the quality of life and enhance health promotion. Using the studies and cooperation actions conducted by the Urban Research Laboratory (LABINUR/FEC-Unicamp) as a reference, this article describes relevant aspects of the PNPS that have an interface with urban planning policies in Brazil. An increase in interdisciplinary and inter-sectoral measures related to the new PNPS after the passing of Ordinance 2.446/14 was identified, which include: mobility and accessibility; safe development (sanitation, housing and transport); healthy eating with social inclusion and reduction of poverty (community vegetable gardens); corporal activities and physical exercise and the enhancement of urban spaces. The conclusion drawn is that social participation, inter-sectoral activities and the role of the university are important aspects for the promotion of healthy cities. PMID- 27276543 TI - Common Elements Treatment Approach based on a Cognitive Behavioral Intervention: implementation in the Colombian Pacific. AB - Due to the limited supply of mental health services for Afro-Colombian victims of violence, a Common Elements Treatment Approach (CETA) intervention has been implemented in the Colombian Pacific. Given the importance of improvement in mental health interventions for this population, it is necessary to characterize this process. This article seeks to describe the implementation of CETA for Afro Colombian victims of violence in Buenaventura and Quibdo, Colombia through case studieswith individual in-depth interviews with Lay Psychosocial Community Workers (LPCW), supervisors, and coordinators responsible for implementing CETA. From this six core categories were obtained: 1. Effect of armed conflict and poverty 2. Trauma severity 3. Perceived changes with CETA 4. Characteristics and LPCW's performance 5. Afro-Colombian culturalapproach and 6. Strategies to promote users' well-being.Colombian Pacific's scenario implies several factors, such as the active armed conflict, economic crisis, and lack of mental health care resources, affecting the implementation process and the intervention effects. This implies the need to establish and strengthen partnerships between institutions in order to administer necessary mental health care for victims of violence in the Colombian Pacific. PMID- 27276544 TI - [The promotion of health of the Brazilian female and healthy eating: discourses and opinions printed in the Brazilian newspaper Folha de Sao Paulo]. AB - The study identifies the discourse and opinions about women's health in relation to their eating habits by means of qualitative research using the journalistic discourse analysis method of the Folha de Sao Paulo newspaper. Based on the selection of texts on health, women's health and nutrition published throughout the year 2013, the sample resulted in seven journalistic texts, in which voices from the scientific universe related to research, quotes from journals, scientific associations and the opinion of health professionals and researchers were predominantly identified. However, the discourse of women in general about their health rarely appears in the sample analyzed. The main topics were related to health risks and the connection with diet or supplements, as well as pregnancy. The predominant content discourse related to health risk and its relationship with eating habits, nutrition or supplements, as well as pregnancy and/or the manner of delivery; health as a commodity associated with products or procedures, such as diets, dietary supplements, drugs and bariatric surgery, with no room for the promotion of health and healthy eating. PMID- 27276545 TI - [Prenatal care and risk factors associated with premature birth and low birth weight in the a capital in the Brazilian Northeast]. AB - The main determinants of the risk of mortality in the neonatal period are low birth weight and premature birth. The study sought to analyze the adequacy of prenatal care and risk factors associated with premature birth and low birth weight in a northeastern Brazilian capital. This is a case-control study. A model for adequacy of prenatal conditions composed of four indicators was created. Descriptive statistics for univariate analysis were used; as well as Wald linear trend tests, Student's t and chi-square test for bivariate analysis and multiple logistic regression for multivariate analysis with p <0.05. Multivariate analysis showed that poor education, not performing gainful activity, caesarean section, oligohydramnios, placental abruption and pre-eclampsia are independent factors associated with premature birth and/or low birth weight. For adequacy of prenatal care, variable indicator III remained significant, showing that mothers who had inadequate prenatal care had an increased chance for the occurrence of the outcome, highlighting the need for adequate public health policies of care for pregnant women in the municipality under scrutiny. PMID- 27276546 TI - [Awareness and education regarding sexually transmitted diseases among undergraduate students]. AB - Sexually transmitted diseases (STDs) are the main global cause of acute illness and death and represent a high socioeconomic cost. Undergraduate students are highly exposed to STDs. The research developed at UNICAMP sought to quantify and generate self-perception of knowledge(or lack thereof) about STDs, as well as evaluate the interest of the students in a course on the topic. The data collection instrument was a questionnaire sent electronically to students about to graduate at the end of 2011 and to freshmen in 2012. The questionnaire was answered by 1,448 seniors and 371 freshmen. Twenty percent of seniors and 38% of freshmen had no sexual activity. Among sexually active students, 26.9% had no regular partner and 28.2% more than two partners per year. The condom was used by 99% of students, but less than 20% used them appropriately. About 80% were unaware that condoms do not provide protection outside the barrier area; they intended to read more about STDs and learnt something about the subject. Nearly half of the students considered that a course should be offered to all undergraduates. These findings will be of use in defining strategies for prevention and the teaching tool could be used in other learning environments. PMID- 27276548 TI - Neutron Scattering from Polymers: Five Decades of Developing Possibilities. AB - The first three decades of my research career closely map the development of neutron scattering techniques for the study of molecular behavior. At the same time, the theoretical understanding of organization and motion of polymer molecules, especially in the bulk state, was developing rapidly and providing many predictions crying out for experimental verification. Neutron scattering is an ideal technique for providing the necessary evidence. This autobiographical essay describes the applications by my research group and other collaborators of increasingly sophisticated neutron scattering techniques to observe and understand molecular behavior in polymeric materials. It has been a stimulating and rewarding journey. PMID- 27276547 TI - Effects of cadmium on lipid metabolism in female estuarine crab, Chiromantes dehaani. AB - Due to the nature of their habitat, which contains a high level of pollutants, estuarine crabs are at great risk of exposure to contaminants such as cadmium. Thus, in this study, the effects of cadmium on lipid metabolism were investigated in estuarine crab Chiromantes dehaani. Adult female estuarine crabs were randomly exposed to 0.05, 0.1, 0.5, and 1mg/L of CdCl2 for 7, 14 and 21days, after which the lipid contents of the hepatopancreas and ovary were measured. Also, the substance contents and the activities of the enzyme in lipid digestion, lipid synthesis and lipid transport metabolism were analyzed. The results showed that the lipid contents in the hepatopancreas and ovary of the exposed crabs decreased after prolonged exposure to cadmium compared to the control. The lipase activity decreased while the activities of fatty acid synthase and acetyl coenzyme A in the hepatopancreas increased on day 7 but decreased on days 14 and 21. Moreover, the change in non-esterified fatty acid level was similar to fatty acid synthase. The level of low-density lipoprotein increased in the exposed crabs compared to the control group while the level of high-density lipoprotein and the activity of lipoprotein lipase decreased at a higher concentration of cadmium and longer exposure time. These observations suggest that cadmium decreases the lipid content by weakening the ability of digestion, transportation and synthase of lipid, thus affecting hepatopancreas and ovary indices. PMID- 27276549 TI - A Selection of Recent Advances in C1 Chemistry. AB - This review presents a selection of recent publications related to the chemistry and catalysis of C1 molecules, including methane, methanol, carbon monoxide, and carbon dioxide. These molecules play an important role in the current supply of energy and chemicals and will likely become even more relevant because of the need to decarbonize fuels (shift from coal to natural gas) in line with CO2 capture and use to mitigate global warming, as well as a gradual shift on the supply side from crude oil to natural gas. This review includes both recent industrial developments, such as the huge increase in methanol-to-olefins capacity build in China and the demonstration of oxidative coupling of methane, and scientific developments in these chemistries facilitated by improved capabilities in, for example, analytical tools and computational modeling. PMID- 27276550 TI - Polymer Thin Films and Surface Modification by Chemical Vapor Deposition: Recent Progress. AB - Chemical vapor deposition (CVD) polymerization uses vapor phase monomeric reactants to synthesize organic thin films directly on substrates. These thin films are desirable as conformal surface engineering materials and functional layers. The facile tunability of the films and their surface properties allow successful integration of CVD thin films into prototypes for applications in surface modification, device fabrication, and protective films. CVD polymers also bridge microfabrication technology with chemical and biological systems. Robust coatings can be achieved via CVD methods as antifouling, anti-icing, and antihydrate surfaces, as well as stimuli-responsive or biocompatible polymers and novel nanostructures. Use of low-energy input, modest vacuum, and room temperature substrates renders CVD polymerization compatible with thermally sensitive substrates and devices. Compared with solution-based methods, CVD is particularly useful for insoluble materials, such as electrically conductive polymers and controllably crosslinked networks, and has the potential to reduce environmental, health, and safety impacts associated with solvents. This review discusses the relevant background and selected applications of recent advances by two methods that display and use the high retention of the organic functional groups from their respective monomers, initiated CVD (iCVD) and oxidative CVD (oCVD) polymerization. PMID- 27276551 TI - Thermodynamics of Bioreactions. AB - Thermodynamic principles have been applied to enzyme-catalyzed reactions since the beginning of the 1930s in an attempt to understand metabolic pathways. Currently, thermodynamics is also applied to the design and analysis of biotechnological processes. The key thermodynamic quantity is the Gibbs energy of reaction, which must be negative for a reaction to occur spontaneously. However, the application of thermodynamic feasibility studies sometimes yields positive Gibbs energies of reaction even for reactions that are known to occur spontaneously, such as glycolysis. This article reviews the application of thermodynamics in enzyme-catalyzed reactions. It summarizes the basic thermodynamic relationships used for describing the Gibbs energy of reaction and also refers to the nonuniform application of these relationships in the literature. The review summarizes state-of-the-art approaches that describe the influence of temperature, pH, electrolytes, solvents, and concentrations of reacting agents on the Gibbs energy of reaction and, therefore, on the feasibility and yield of biological reactions. PMID- 27276552 TI - Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives. AB - Stem cells and other functionally defined therapeutic cells (e.g., T cells) are promising to bring hope of a permanent cure for diseases and disorders that currently cannot be cured by conventional drugs or biological molecules. This paradigm shift in modern medicine of using cells as novel therapeutics can be realized only if suitable manufacturing technologies for large-scale, cost effective, reproducible production of high-quality cells can be developed. Here we review the state of the art in therapeutic cell manufacturing, including cell purification and isolation, activation and differentiation, genetic modification, expansion, packaging, and preservation. We identify current challenges and discuss opportunities to overcome them such that cell therapies become highly effective, safe, and predictively reproducible while at the same time becoming affordable and widely available. PMID- 27276553 TI - Polymer Fluid Dynamics: Continuum and Molecular Approaches. AB - To solve problems in polymer fluid dynamics, one needs the equations of continuity, motion, and energy. The last two equations contain the stress tensor and the heat-flux vector for the material. There are two ways to formulate the stress tensor: (a) One can write a continuum expression for the stress tensor in terms of kinematic tensors, or (b) one can select a molecular model that represents the polymer molecule and then develop an expression for the stress tensor from kinetic theory. The advantage of the kinetic theory approach is that one gets information about the relation between the molecular structure of the polymers and the rheological properties. We restrict the discussion primarily to the simplest stress tensor expressions or constitutive equations containing from two to four adjustable parameters, although we do indicate how these formulations may be extended to give more complicated expressions. We also explore how these simplest expressions are recovered as special cases of a more general framework, the Oldroyd 8-constant model. Studying the simplest models allows us to discover which types of empiricisms or molecular models seem to be worth investigating further. We also explore equivalences between continuum and molecular approaches. We restrict the discussion to several types of simple flows, such as shearing flows and extensional flows, which are of greatest importance in industrial operations. Furthermore, if these simple flows cannot be well described by continuum or molecular models, then it is not necessary to lavish time and energy to apply them to more complex flow problems. PMID- 27276554 TI - Conformational Equilibrium and Potential Energy Functions of the O-H Internal Rotation in the Axial and Equatorial Species of 1-Methylcyclohexanol. AB - The rotational spectra of four conformers (At, Ag, Et, Eg) of the tertiary alcohol 1-methylcyclohexanol were assigned by pulsed jet Fourier transform microwave spectroscopy. The transitions of two gauche conformers were split in two separated component lines, but it was not possible-from the available measured transitions-to accurately determine their vibrational DeltaE0+0- ground state splittings, respectively. In addition, the rotational spectra of the four OD deuterated isotopologues were measured and assigned. For the gauche species of this isotopologue we were able to determine the tunneling splittings, DeltaE0+0 (Ag, OD) = 15.581(5) GHz and DeltaE0+0-(Eg, OD) = 18.17(3) GHz, respectively. From these splittings the inversion barriers for Ag and Eg were determined, by using a flexible model, to be B2(Ag) = 356(10) and B2(Eg) = 320(10) cm(-1), respectively. PMID- 27276556 TI - Kinetic Resolution of Racemic and Branched Monosubstituted Allylic Acetates by a Ruthenium-Catalyzed Regioselective Allylic Etherification. AB - We demonstrated the kinetic resolution of racemic and branched monosubstituted allylic acetates by a ruthenium-catalyzed regioselective allylic etherification. The reaction was effectively catalyzed by the chiral ruthenium catalyst, which was generated by [RuCl2(p-cymene)]2 and (S,S)-iPr-pybox and a catalytic amount of TFA, and both the allylic etherification product and recovered allylic acetate were obtained as an enantiomerically enriched form with up to a 103 s value. PMID- 27276555 TI - c-FOS expression in the visual system of tree shrews after monocular inactivation. AB - Tree shrews possess an unusual segregation of ocular inputs to sublayers rather than columns in the primary visual cortex (V1). In this study, the lateral geniculate nucleus (LGN), superior colliculus (SC), pulvinar, and V1 were examined for changes in c-FOS, an immediate-early gene, expression after 1 or 24 hours of monocular inactivation with tetrodotoxin (TTX) in tree shrews. Monocular inactivation greatly reduced gene expression in LGN layers related to the blocked eye, whereas normally high to moderate levels were maintained in the layers that receive inputs from the intact eye. The SC and caudal pulvinar contralateral to the blocked eye had greatly (SC) or moderately (pulvinar) reduced gene expressions reflective of dependence on the contralateral eye. c-FOS expression in V1 was greatly reduced contralateral to the blocked eye, with most of the expression that remained in upper layer 4a and lower 4b and lower layer 6 regions. In contrast, much of V1 contralateral to the active eye showed normal levels of c-FOS expression, including the inner parts of sublayers 4a and 4b and layers 2, 3, and 6. In some cases, upper layer 4a and lower 4b showed a reduction of gene expression. Layers 5 and sublayer 3c had normally low levels of gene expression. The results reveal the functional dominance of the contralateral eye in activating the SC, pulvinar, and V1, and the results from V1 suggest that the sublaminar organization of layer 4 is more complex than previously realized. J. Comp. Neurol. 525:151-165, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27276557 TI - WGO Celebrates World Digestive Health Day 2016 Your Diet and Gut Health! PMID- 27276559 TI - Saving Tiny Tim--Pediatrics and Childhood Poverty in the United States. PMID- 27276560 TI - The Hell of Syria's Field Hospitals. PMID- 27276564 TI - IMAGES IN CLINICAL MEDICINE. Hyperkalemia after Missed Hemodialysis. PMID- 27276563 TI - Renal Complications of Hematopoietic-Cell Transplantation. PMID- 27276561 TI - Genomic Classification and Prognosis in Acute Myeloid Leukemia. AB - BACKGROUND: Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of AML and informs clinical practice. METHODS: We enrolled a total of 1540 patients in three prospective trials of intensive therapy. Combining driver mutations in 111 cancer genes with cytogenetic and clinical data, we defined AML genomic subgroups and their relevance to clinical outcomes. RESULTS: We identified 5234 driver mutations across 76 genes or genomic regions, with 2 or more drivers identified in 86% of the patients. Patterns of co-mutation compartmentalized the cohort into 11 classes, each with distinct diagnostic features and clinical outcomes. In addition to currently defined AML subgroups, three heterogeneous genomic categories emerged: AML with mutations in genes encoding chromatin, RNA-splicing regulators, or both (in 18% of patients); AML with TP53 mutations, chromosomal aneuploidies, or both (in 13%); and, provisionally, AML with IDH2(R172) mutations (in 1%). Patients with chromatin-spliceosome and TP53-aneuploidy AML had poor outcomes, with the various class-defining mutations contributing independently and additively to the outcome. In addition to class-defining lesions, other co occurring driver mutations also had a substantial effect on overall survival. The prognostic effects of individual mutations were often significantly altered by the presence or absence of other driver mutations. Such gene-gene interactions were especially pronounced for NPM1-mutated AML, in which patterns of co-mutation identified groups with a favorable or adverse prognosis. These predictions require validation in prospective clinical trials. CONCLUSIONS: The driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT00146120.). PMID- 27276565 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 17-2016. A 60-Year-Old Woman with Increasing Dyspnea. PMID- 27276567 TI - Roads Diverge--A Robert Frost View of Leukemia Development. PMID- 27276562 TI - Exome Sequencing and the Management of Neurometabolic Disorders. AB - BACKGROUND: Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. METHODS: To uncover the genetic basis of potentially treatable inborn errors of metabolism, we combined deep clinical phenotyping (the comprehensive characterization of the discrete components of a patient's clinical and biochemical phenotype) with whole-exome sequencing analysis through a semiautomated bioinformatics pipeline in consecutively enrolled patients with intellectual developmental disorder and unexplained metabolic phenotypes. RESULTS: We performed whole-exome sequencing on samples obtained from 47 probands. Of these patients, 6 were excluded, including 1 who withdrew from the study. The remaining 41 probands had been born to predominantly nonconsanguineous parents of European descent. In 37 probands, we identified variants in 2 genes newly implicated in disease, 9 candidate genes, 22 known genes with newly identified phenotypes, and 9 genes with expected phenotypes; in most of the genes, the variants were classified as either pathogenic or probably pathogenic. Complex phenotypes of patients in five families were explained by coexisting monogenic conditions. We obtained a diagnosis in 28 of 41 probands (68%) who were evaluated. A test of a targeted intervention was performed in 18 patients (44%). CONCLUSIONS: Deep phenotyping and whole-exome sequencing in 41 probands with intellectual developmental disorder and unexplained metabolic abnormalities led to a diagnosis in 68%, the identification of 11 candidate genes newly implicated in neurometabolic disease, and a change in treatment beyond genetic counseling in 44%. (Funded by BC Children's Hospital Foundation and others.). PMID- 27276566 TI - A New Label for Mifepristone. PMID- 27276568 TI - Targeting a Long Noncoding RNA in Breast Cancer. PMID- 27276569 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276570 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276571 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276572 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276573 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276574 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276575 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276576 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276577 TI - A Randomized Trial of Intensive versus Standard Blood-Pressure Control. PMID- 27276579 TI - Abdominal Sacrocolpopexy with Burch Colposuspension to Reduce Urinary Stress Incontinence. PMID- 27276578 TI - Corrections to Report of a Trial of Burch Colposuspension. PMID- 27276580 TI - IMAGES IN CLINICAL MEDICINE. Ventricular Septal Defect after Acute Myocardial Infarction. PMID- 27276582 TI - Cinacalcet for Symptomatic Hypercalcemia Caused by AP2S1 Mutations. PMID- 27276581 TI - INTERACTIVE MEDICAL CASE. A Woman with Dyspnea and Altered Mental Status. PMID- 27276583 TI - Peapod-Like Carbon-Encapsulated Cobalt Chalcogenide Nanowires as Cycle-Stable and High-Rate Materials for Sodium-Ion Anodes. AB - Peapod-like carbon-encapsulated cobalt chalcogenide nanowires are designed and synthesized by a facile method. The nanowires show excellent electrochemical performance for sodium storage, suggesting that chalcogenides, especially selenides, have potential as advanced anodes for sodium-ion batteries. PMID- 27276584 TI - CRISPR guide RNA design for research applications. AB - The rapid rise of CRISPR as a technology for genome engineering and related research applications has created a need for algorithms and associated online tools that facilitate design of on-target and effective guide RNAs (gRNAs). Here, we review the state of the art in CRISPR gRNA design for research applications of the CRISPR-Cas9 system, including knockout, activation, and inhibition. Notably, achieving good gRNA design is not solely dependent on innovations in CRISPR technology. Good design and design tools also rely on availability of high quality genome sequence and gene annotations, as well as on availability of accumulated data regarding off-targets and effectiveness metrics. PMID- 27276634 TI - Pediatric Tibial Osteomyelitis. AB - BACKGROUND: Osteomyelitis shows a strong predilection for the tibia in the pediatric population and is a significant source of complications. The purpose of this article is to retrospectively review a large series of pediatric patients with tibial osteomyelitis. We compare our experience with that in the literature to determine any factors that may aid diagnosis and/or improve treatment outcomes. METHODS: A 10-year retrospective review was performed of clinical records of all cases of pediatric tibial osteomyelitis managed at the 2 children's orthopaedic departments in the Auckland region. The Osteomyelitis Database was used to identify all cases between 1997 and 2007, at Starship Children's Hospital, and 1998 and 2008 at Middlemore's Kids First Hospital. RESULTS: One hundred ninety-one patients fulfilled the inclusion criteria, and had a review of clinical notes and relevant investigations. The average duration of symptoms before presentation to hospital was 5.7 days. Less than 40% of patients had a recent episode of trauma. Almost 60% of patients could not bear weight on admission. Over 40% of patients had a temperature above 38 degrees C. Erythrocyte sedimentation rate was elevated in 78% and the C-reactive protein was elevated in 90% of patients. In total, 42% of blood cultures and almost 75% of tissue cultures were positive, with Staphylococcus aureus being the most commonly cultured organism. X-rays, bone scans, and magnetic resonance imaging were all used to aid the diagnosis. About 43% of patients had surgery. Treatment length was an average of 2 weeks 6 days of intravenous antibiotics followed by 3 weeks 2 days of oral treatment. Six postsurgical complications and 46 readmissions were noted: 25 for relapse, with the remainder due to social and antibiotic-associated complications. CONCLUSIONS: Although generally diagnosed on presentation, pediatric tibial osteomyelitis can require more sophisticated investigations and prolonged management. Treatment with intravenous and oral antibiotics and surgical debridement where indicated can lead to a good clinical outcome, although complications are often noted. LEVEL OF EVIDENCE: Level IV-Prognostic study. PMID- 27276635 TI - The Anterolateral Ligament of the Knee: An Inconsistent Finding in Pediatric Cadaveric Specimens. AB - BACKGROUND: The anterolateral ligament (ALL) of the knee has been identified as a structure that limits internal rotation, and thus, affects the pivot shift mechanism. It has previously been reported in a high percentage of adult subjects. The purpose of the current study was to evaluate whether the ALL could be identified on pediatric cadaveric knee specimens and compare these findings to previously published reports. METHODS: Eight skeletally immature cadaver knee specimens were examined through gross dissection: ages 3 months, 4 months, 1 year, 2 years, 3 years, 3 years, 8 years, and 10 years. There were 3 male and 5 female (7 right, 1 left) specimens. The presence or absence of the ALL was documented in each specimen, through dissection, intermittent internal and external rotation of the tibia, and anterior translation of the tibia, to produce tension of the lateral collateral tissues and joint capsule. These dissections were performed by a group of fellowship-trained orthopaedic surgeons. RESULTS: The iliotibial band, entire lateral joint capsule, lateral collateral ligament, and popliteus were readily identified in each specimen. In 7 specimens, a distinct ALL structure was not identified during dissection. The ALL was identified in 1 of 8 specimens (1-year-old female, right knee). The ALL was further delineated under applied internal rotational stress. CONCLUSIONS: Previous research has suggested that this ligament is present in the majority of adult specimens. This finding was not reproduced in the current study of pediatric cadaveric specimens, where only one of 8 specimens had an identifiable ALL. This suggests that this ligament may develop later in life, after physiological loads are applied to the joint capsule. Further research in both adult and pediatric knees needs to be conducted to further elucidate the development of this ligament, and the role of this structure in knee stability. CLINICAL RELEVANCE: The ALL is a knee ligament that has been described in adults. However, it is unclear whether this structure is present or fully developed in younger populations. The current study sought to identify the ALL in pediatric cadaver knee specimens, identifying this structure in only one of 8 specimens. The findings of this study suggest that the ALL may be an inconsistent structure in the pediatric population. PMID- 27276636 TI - Arthroscopic Treatment of Discoid Lateral Meniscus Tears in Children With Achondroplasia. AB - BACKGROUND: Achondroplasia is the most common form of skeletal dysplasia that presents to the pediatric orthopaedist. More than half of achondroplasia patients are affected with knee pain. It is thought that the majority of this pain may be due to spinal stenosis, hip pathology, or knee malalignment. Discoid menisci can be a source of lateral knee joint pain in skeletally immature patients in general. We present the first case series of patients with achondroplasia who had symptomatic discoid lateral menisci treated with arthroscopic knee surgery. METHODS: The charts of 6 patients (8 knees) with achondroplasia who underwent arthroscopic knee surgery for symptomatic discoid lateral menisci were collected. History and physical examination data, magnetic resonance imaging findings, and operative reports were reviewed. Meniscal tear configuration and treatment type (meniscectomy vs. repair) were noted. RESULTS: Each patient was found to have a tear of the discoid meniscus. All menisci were treated with saucerization. In addition, meniscal repair was performed in 2 cases, partial meniscectomy in 3 cases, and subtotal meniscectomy in 3 cases. Two patients had bilateral discoid meniscal tears which were treated. Average follow-up was 2.4 years (range, 1 to 4.5 y) and the average pediatric International Knee Documentation Committee (pedi IKDC) score was 85.3% (range, 75% to 95.4%). At final follow-up, all patients were pain free and able to return to full activities. CONCLUSIONS: Discoid meniscus tears may be a source of lateral joint line pain in patients with achondroplasia. These injuries can be successfully treated with arthroscopic surgery in this patient population. Future studies need to be done to determine the exact incidence of discoid menisci in achondroplasia patients and also to determine whether there is a genetic relationship between the 2 conditions. LEVEL OF EVIDENCE: Level IV-case series. PMID- 27276637 TI - Vitamin D Status in Blount Disease. AB - INTRODUCTION: Blount disease can be defined as idiopathic proximal tibial vara. Several etiologies including the mechanical theory have been described. Obesity is the only causative factor proven to be associated with Blount disease. The aim of this study is to assess if there is an association of vitamin D deficiency and Blount disease. METHODS: This a retrospective study of preoperative and postoperative patients with Blount disease who were screened for vitamin D deficiency. Patients with genu varum due to confirmed vitamin D deficiency and rickets were excluded. The study patients had the following blood tests done: calcium, phosphate, alkaline phosphatase, parathyroid, and 25-hydroxyvitamin D (25(OH)D) hormones. RESULTS: We recruited 50 patients. The mean age of these patients was 10.4 years (SD+/-3.88) with average body mass index of 28.7 kg/m (+/ 10.2). Thirty (60%) patients were diagnosed with infantile, 4 (8%) juvenile, and 16 (32%) adolescent Blount disease. Eight (16%) patients were found to be vitamin D deplete (25(OH)D levels <50 nmol/L). Of these, 8 patients, 6 were insufficient (25(OH)D levels between 30 and 50 nmol/L) and the other 2 were deficient (25(OH)D levels <30 nmol/L). CONCLUSIONS: This study showed that the prevalence of vitamin D deficiency in children with Blount disease was similar to that of healthy children living in Johannesburg. There is no evidence that vitamin D deficiency is a factor in causing Blount disease. LEVEL OF EVIDENCE: Level III-retrospective study. PMID- 27276638 TI - Correspondence. PMID- 27276639 TI - Correspondence. PMID- 27276640 TI - Light Pipe Guard-Assisted Cataract Extraction In Combined Pars Plana Vitrectomy. PMID- 27276641 TI - Correspondence. PMID- 27276642 TI - Correspondence. PMID- 27276643 TI - Correspondence. PMID- 27276644 TI - Reply. PMID- 27276645 TI - Reply. PMID- 27276646 TI - Reply. PMID- 27276647 TI - Reply. PMID- 27276649 TI - Reply. PMID- 27276648 TI - Correspondence. PMID- 27276650 TI - Molten salts and energy related materials. AB - Molten salts have been known for centuries and have been used for the extraction of aluminium for over one hundred years and as high temperature fluxes in metal processing. This and other molten salt routes have gradually become more energy efficient and less polluting, but there have been few major breakthroughs. This paper will explore some recent innovations that could lead to substantial reductions in the energy consumed in metal production and in carbon dioxide production. Another way that molten salts can contribute to an energy efficient world is by creating better high temperature fuel cells and novel high temperature batteries, or by acting as the medium that can create novel materials that can find applications in high energy batteries and other energy saving devices, such as capacitors. Carbonate melts can be used to absorb carbon dioxide, which can be converted into C, CO and carbon nanoparticles. Molten salts can also be used to create black silicon that can absorb more sunlight over a wider range of wavelengths. Overall, there are many opportunities to explore for molten salts to play in an efficient, low carbon world. PMID- 27276651 TI - Development of a modified QuEChERS method for the determination of veterinary antibiotics in swine manure by liquid chromatography tandem mass spectrometry. AB - A QuEChERS (quick, easy, cheap, effective, rugged and safe) based methodology was developed for the rapid, simultaneous quantification and identification of 26 veterinary drugs in swine manure by liquid chromatography tandem mass spectrometry. The selected antibiotics included tetracyclines, sulfonamides, macrolides, fluoroquinolones, lincosamides and pleuromutilins. This is the first study to determine pleuromutilin levels in manure. The QuEChERS process involved two simple steps. First, sample extraction with methanol: acetonitrile: 0.1M EDTA McIlvaine buffer followed by phase separation with MgSO4: NaCl addition. The supernatant was then extracted and cleaned by dispersive solid-phase extraction using a primary-secondary amine (PSA) and octadecylsilane (C18) support. The proposed method provides a linearity in the range of 1-500ngmL-1 and linear regression coefficients (r) were greater than 0.996. MDL and MQL ranged between 0.01-1.86MUgkg(-1) and 0.05-5.91MUgkg(-1), respectively. Recoveries ranged from 61.39 to 105.65% with the exception of sulfaquinoxaline (55.7-56.8%) and valnemulin (33.7-37.7%). This method resulted in good precision (repeatability and reproducibility) and relative standard deviations less than 17% within the same day, and lower than 20% between days. The method was then applied to study the swine manure samples collected from Guangdong, China. Chlortetracycline, tetracycline, doxycycline, sulfadimidine and tilmicosin were detected in all samples indicating high residuals in manure. In fact tilmicosin was detected at 14400MUgkg(-1) suggesting that prudent treatment of manure should be conducted to prevent environmental contamination. In conclusion, this workflow can provide a simpler and more cost-effective alternative to conventional methods and is compatible with processing large sample numbers over a short time period. PMID- 27276652 TI - Reticulon 4A/Nogo-A influences the distribution of Kir4.1 but is not essential for potassium conductance in retinal Muller glia. AB - In the adult retina, we have previously shown that Nogo-A was highly expressed in Muller glia. However, the role of Nogo-A in the glial cell physiology is not clear. In this study, we investigated the possible influence that Nogo-A may exert on other polarized molecules in Muller cells, in particular inwardly rectifying potassium channel 4.1 (Kir4.1) and aquaporin 4 (AQP4) that respectively control potassium and water exchange in glial cells. Our results showed that adenovirus-mediated Nogo-A overexpression with AdNogo-A increased the immunofluorescent signal of Kir4.1 in rat Muller cell line 1 (rMC-1) cells but did not change its expression level by Western blotting. In vivo, AdNogo-A induced ectopic Kir4.1 immunoreactivity throughout the radial processes of Muller cells compared with AdLacZ control virus. Surprisingly, AdNogo-A did not modify the distribution of Dp71 and AQP4 that are common binding partners for Kir4.1 in the dystrophin-associated protein (DAP) complex anchored at the plasma membrane of Muller glia. Immunoprecipitation experiments revealed molecular interactions between Nogo-A and Kir4.1. In Nogo-A KO mouse retinae, the distribution of Kir4.1 was not different from that observed in Wild-Type (WT) animals. In addition, potassium conductance did not change in freshly dissociated Nogo-A KO Muller glia compared with WT cells. In summary, the increase of Nogo-A expression can selectively influence the distribution of Kir4.1 in glia but is not essential for Kir4.1-mediated potassium conductance at the plasma membrane in physiological conditions. Nogo-A-Kir4.1 interactions may, however, contribute to pathological processes taking place in the retina, for instance, after ischemia. PMID- 27276654 TI - OMIP-033: A comprehensive single step staining protocol for human T- and B-cell subsets. PMID- 27276653 TI - Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice. AB - Silibinin was reported to be effective in reversing the learning and memory deficits of several AD animal models. These improvements are thought to be regulated by various factors, including antioxidative stress, inhibition of acetylcholinesterase activity and Abeta aggregation. However, there are still no reports that demonstrate the effect of silibinin on microglia activation in vivo. Thus, in this study, we used the senescence-accelerated mouse (SAMP8) strain to test the effects of silibinin on behavioral impairments and microglia activation induced neuroinflammation. Silibinin treatment significantly rescued memory deficits in novel object recognition test and Morris water maze test. Silibinin treatment significantly attenuated microglial activation; down-regulated the level of the proinflammatory cytokine IL-6, anti-inflammatory cytokine IL-4, and inflammation-associated proteins, iNOS and COX-2; and further modulated MAPK to protect neural cells. These results suggest that silibinin could be a potential candidate for the therapy of neurodegenerative disorders. PMID- 27276655 TI - Inverse Association Between Atopy and Melanoma: A Case-control Study. AB - Heightened cutaneous immune surveillance in atopic patients may inhibit development of melanoma. The aim of this study was to analyse the association between atopy and melanoma (development and outcome). A total of 188 cases of melanoma and 596 healthy controls were interviewed by telephone with a standardized questionnaire on atopic, demographic and melanoma characteristics. Cases were matched with controls on important confounders (age, sex, sunburn sensitivity, hair colour, number of moles, sunburn as juvenile, ever solarium, familial melanoma). Melanoma outcome data (disease relapse and death) within cases were retrieved. Analysis showed a general inverse association between atopy and melanoma development, but this was statistically significant only for a history of personal atopy (odds ratio 0.53, 95% confidence interval: 0.30-0.96, p value = 0.04). Among melanoma patients, atopy did not affect survival or progression. In conclusion, this study suggests an inverse association between a history of atopy and melanoma development, but not with disease progression. PMID- 27276656 TI - Achieving Superior Two-Way Actuation by the Stress-Coupling of Nanoribbons and Nanocrystalline Shape Memory Alloy. AB - Inspired by the driving principle of traditional bias-type two-way actuators, we developed a novel two-way actuation nanocomposite wire in which a massive number of Nb nanoribbons with ultralarge elastic strains are loaded inside a shape memory alloy (SMA) matrix to form a continuous array of nanobias actuation pairs for two-way actuation. The composite exhibits a two-way actuation strain of 3.2% during a thermal cycle and an actuation stress of 934 MPa upon heating, which is about twice as high as that (~500 MPa) found in reported two-way SMAs. Upon cooling, the composite shows an actuation stress of 134 MPa and a mechanical work output of 1.08 * 10(6) J/m(3), which are about three and five times higher than those of reported two-way SMAs, respectively. It was revealed that the massive number of Nb nanoribbons in the compressive state provides the high actuation stress and high work output upon cooling, and the SMA matrix with high yield strength offers the high actuation stress upon heating. Compared to traditional bias-type two-way actuators, the two-way actuation composite with a small volume and simple construct works well with the miniaturization and simplification of actuators. PMID- 27276657 TI - Phospholipids as cancer biomarkers: Mass spectrometry-based analysis. AB - Lipids, particularly phospholipids (PLs), are key components of cellular membrane. PLs play important and diverse roles in cells such as chemical-energy storage, cellular signaling, cell membranes, and cell-cell interactions in tissues. All these cellular processes are pertinent to cells that undergo transformation, cancer progression, and metastasis. Thus, there is a strong possibility that some classes of PLs are expected to present in cancer cells and tissues in cellular physiology. The mass spectrometric soft-ionization techniques, electrospray ionization (ESI), and matrix-assisted laser desorption/ionization (MALDI) are well-established in the proteomics field, have been used for lipidomic analysis in cancer research. This review focused on the applications of mass spectrometry (MS) mainly on ESI-MS and MALDI-MS in the structural characterization, molecular composition and key roles of various PLs present in cancer cells, tissues, blood, and urine, and on their importance for cancer-related problems as well as challenges for development of novel PL-based biomarkers. The profiling of PLs helps to rationalize their functions in biological systems, and will also provide diagnostic information to elucidate mechanisms behind the control of cancer, diabetes, and neurodegenerative diseases. The investigation of cellular PLs with MS methods suggests new insights on various cancer diseases and clinical applications in the drug discovery and development of biomarkers for various PL-related different cancer diseases. PL profiling in tissues, cells and body fluids also reflect the general condition of the whole organism and can indicate the existence of cancer and other diseases. PL profiling with MS opens new prospects to assess alterations of PLs in cancer, screening specific biomarkers and provide a basis for the development of novel therapeutic strategies. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:107 138, 2018. PMID- 27276658 TI - Homologues of CsLOB1 in citrus function as disease susceptibility genes in citrus canker. AB - The lateral organ boundary domain (LBD) genes encode a group of plant-specific proteins that function as transcription factors in the regulation of plant growth and development. Citrus sinensis lateral organ boundary 1 (CsLOB1) is a member of the LBD family and functions as a disease susceptibility gene in citrus bacterial canker (CBC). Thirty-four LBD members have been identified from the Citrus sinensis genome. We assessed the potential for additional members of LBD genes in citrus to function as surrogates for CsLOB1 in CBC, and compared host gene expression on induction of different LBD genes. Using custom-designed transcription activator-like (TAL) effectors, two members of the same clade as CsLOB1, named CsLOB2 and CsLOB3, were found to be capable of functioning similarly to CsLOB1 in CBC. RNA sequencing and quantitative reverse transcription polymerase chain reaction analyses revealed a set of cell wall metabolic genes that are associated with CsLOB1, CsLOB2 and CsLOB3 expression and may represent downstream genes involved in CBC. PMID- 27276659 TI - New Giant Fullerenes Identified as Chloro Derivatives: Isolated-Pentagon-Rule C108(1771)Cl12 and C106(1155)Cl24 as well as Nonclassical C104Cl24. AB - High temperature chlorination of HPLC fractions of higher fullerenes followed by single crystal X-ray diffraction with the use of synchrotron radiation resulted in the structure determination of IPR C106(1155)Cl24 and IPR C108(1771)Cl12. C106(1155)Cl24 is cocrystallized with C104Cl24, a chloride of the nonclassical isomer of C104. The moderately stable isomer C106(1155) and the most stable C108(1771) represent so far the largest pristine fullerenes with known cages. PMID- 27276660 TI - Atomic Resolution Insights into the Structural Aggregations and Optical Properties of Neat Imidazolium-Based Ionic Liquids. AB - A fundamental understanding of the structural heterogeneity and optical properties of ionic liquids is crucial for their potential applications in catalysis, optical measurement, and solar cells. Herein, a synergistic approach combining molecular dynamics simulations, excited-state calculations, and statistical analysis was used to explore the explicit correlation between the structural and optical properties of one imidazolium amino acid-based ionic liquid, 1-butyl-3-methylimidazolium glycine. The estimated absorption spectrum successfully rationalizes the unusual and non-negligible absorption band beyond 300 nm for the neat imidazolium-based ionic liquid. The absorption behavior of imidazolium-based ionic liquids is shown to be sensitive to the details of their locally heterogeneous environments. We quantitatively highlight the imidazolium moiety and its various molecular aggregations, rather than the monomeric imidazolium moiety, that are responsible for the absorption characteristics. These results would improve our understanding of the preliminary interplay between structural heterogeneity and optical properties for neat imidazolium based ionic liquids. PMID- 27276661 TI - Tailoring the surface of ZnO nanorods into corrugated nanorods via a selective chemical etch method. AB - Using the chemical vapour deposition method, we successfully converted smooth ZnO nanorods (NRs) into corrugated NRs by simply increasing the reaction time. The surface morphology and crystallographic structure of the corrugated NRs were investigated. The corrugated NRs were decorated by alternant [Formula: see text] and [Formula: see text] planes at the exposed side surfaces while the conventional [Formula: see text] planes disappeared. No twinning boundaries were found in the periodically corrugated structures, indicating that they were type II corrugated NRs. Further investigation told us that they were selectively etched. We introduced a hydrothermal method to synthesize the smooth ZnO NRs and then etched them in a tube furnace at 950 degrees C with a flow of carbon monoxide. By separating the growth stage and the selective etching stage, we explicitly demonstrated a successfully selective etching effect on ZnO NRs with a carbon monoxide reducing atmosphere for the first time. An etching mechanism based on the selective reaction between carbon monoxide and the different exposed surfaces was proposed. Our results will improve the understanding of the growth mechanism on coarse or corrugated NRs and provide a new strategy for the application of surface controlled nanostructured materials. PMID- 27276663 TI - Serological evidence of exposure to tick-borne agents in opossums (Didelphis spp.) in the state of Sao Paulo, Brazil. AB - This work involved a serological investigation of tick-borne pathogens in opossums in eight municipalities of the state of Sao Paulo, Brazil. Serum samples from 109 opossums (91 Didelphis aurita and 18 Didelphis albiventris) were tested to detect antibodies to Rickettsia rickettsii (Taiacu strain, 1:64 cut-off) and Ehrlichia canis (Sao Paulo strain, 1:40 cut-off), by indirect immunofluorescence assay (IFA); and against Borrelia burgdorferi (strain G39/40) by enzyme-linked immunosorbent assay (ELISA). The presence of antibodies to anti-R. rickettsii, anti-E. canis and anti-B. burgdorferi was detected in 32 (29.35%), 16 (14.67%) and 30 (27.52%) opossums, respectively. Opossum endpoint titers ranged from 64 to 1,024 for R. rickettsii, from 40 to 160 for E. canis, and from 400 to >51,200 for B. burgdorferi. These serological results suggest that opossums have been exposed to Rickettsia spp., Ehrlichia spp., and B. burgdorferi-related agents in the state of Sao Paulo. Our study underscores the need for further research about these agents in this study area, in view of the occurrence of Spotted Fever and Baggio-Yoshinari Syndrome disease in humans in the state of Sao Paulo, Brazil. PMID- 27276674 TI - Subarachnoid Hemorrhage: A Sharp Needle in a Haystack. PMID- 27276675 TI - Polypeptide N-acetylgalactosaminyltransferase-6 expression independently predicts poor overall survival in patients with lung adenocarcinoma after curative resection. AB - BACKGROUND: Polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) are important glycosyltransferases in cancer, but the clinical role of its individual isoforms is unclear. We investigated the clinical significance and survival relevance of one isoform, GalNAc-T6 in lung adenocarcinoma after curative resection. RESULTS: GalNAc-T6 was identified in 27.8% (55/198) of patients, and statistically indicated advanced TNM stage (P = 0.069). Multivariate analysis showed GalNAc-T6 to be an independent predictor for reduced overall survival of patients (P = 0.027), and the result was confirmed with bootstraping techniques, and on line "Kaplan-Meier Plotter" and "SurvExpress" database analysis, respectively. Moreover, ROC curve demonstrated that GalNAc-T6 expression significantly improved the accuracy of survival prediction. METHODS: With 198 paraffin-embedded tumor samples from lung adenocarcinoma patients, GalNAc-T6 expression was immunohistochemically assessed for the association with clinicopathological parameters. The prognostic significance was evaluated by Cox proportional hazards regression analysis with 1000 bootstraping. "Kaplan-Meier Plotter", "SurvExpress" database analysis, and receiver-operating characteristic (ROC) curve were performed to provide further validation. CONCLUSIONS: GalNAc-T6 expression correlated significantly with advanced TNM stage, and independently predicted worse OS for lung adenocarcinoma. PMID- 27276676 TI - MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8. AB - microRNAs are aberrantly expressed during the development and progression of a variety of human cancers, including colorectal cancer (CRC). Of these microRNAs, microRNA-375 (miR-375) was previously observed to be downregulated in human colorectal cancer(CRC) plasma and tissues, but its functions are largely unknown. Here, we investigated the impact of miR-375 on CRC metastasis. Specifically, miR 375 expression was significantly decreased in human CRC tissues compared with their matched noncancerous tissues (NCTs), and low levels of miR-375 predicted tumor metastatic potential. The up-regulation of miR-375 suppressed colorectal cancer cell migration and invasion in vitro and reduced tumor metastases in murine models established by both orthotopic implantation and spleen injection. Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/beta-catenin signaling by suppressing FZD8. More importantly, FZD8 expression inversely correlated with overall survival in human CRC patients and is a likely independent predictor of survival. Therefore, we concluded that miR-375 functions as a tumor-suppressive microRNA by directly acting upon FZD8, which may serve as a new therapeutic target to inhibit tumor metastasis in CRC. PMID- 27276677 TI - A novel CBL-Bflox/flox mouse model allows tissue-selective fully conditional CBL/CBL-B double-knockout: CD4-Cre mediated CBL/CBL-B deletion occurs in both T cells and hematopoietic stem cells. AB - CBL-family ubiquitin ligases are critical negative regulators of tyrosine kinase signaling, with a clear redundancy between CBL and CBL-B evident in the immune cell and hematopoietic stem cell studies. Since CBL and CBL-B are negative regulators of immune cell activation, elimination of their function to boost immune cell activities could be beneficial in tumor immunotherapy. However, mutations of CBL are associated with human leukemias, pointing to tumor suppressor roles of CBL proteins; hence, it is critical to assess the tumor intrinsic roles of CBL and CBL-B in cancers. This has not been possible since the only available whole-body CBL-B knockout mice exhibit constitutive tumor rejection. We engineered a new CBL-Bflox/flox mouse, combined this with an existing CBLflox/flox mouse to generate CBLflox/flox; CBL-Bflox/flox mice, and tested the tissue-specific concurrent deletion of CBL and CBL-B using the widely used CD4-Cre transgenic allele to produce a T-cell-specific double knockout. Altered T-cell development, constitutive peripheral T-cell activation, and a lethal multi-organ immune infiltration phenotype largely resembling the previous Lck-Cre driven floxed-CBL deletion on a CBL-B knockout background establish the usefulness of the new model for tissue-specific CBL/CBL-B deletion. Unexpectedly, CD4-Cre-induced deletion in a small fraction of hematopoietic stem cells led to expansion of certain non-T-cell lineages, suggesting caution in the use of CD4 Cre for T-cell-restricted gene deletion. The establishment of a new model of concurrent tissue-selective CBL/CBL-B deletion should allow a clear assessment of the tumor-intrinsic roles of CBL/CBL-B in non-myeloid malignancies and help test the potential for CBL/CBL-B inactivation in immunotherapy of tumors. PMID- 27276678 TI - microRNA-558 facilitates the expression of hypoxia-inducible factor 2 alpha through binding to 5'-untranslated region in neuroblastoma. AB - Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Our previous studies have shown that hypoxia-inducible factor 2 alpha (HIF-2alpha), one member of the bHLH-PAS transcription factor family, facilitates the progression of NB under non-hypoxic conditions. However, the mechanisms underlying HIF-2alpha expression in NB still remain largely unknown. Herein, through analyzing the computational algorithm programs, we identified microRNA 558 (miR-558) as a crucial regulator of HIF-2alpha expression in NB. We demonstrated that miR-558 promoted the expression of HIF-2alpha at translational levels in NB cells through recruiting Argonaute 2 (AGO2). Mechanistically, miR 558 directly bound with its complementary site within 5'-untranslated region (5' UTR) to facilitate the binding of AGO2 to eukaryotic translation initiation factor 4E (eIF4E) binding protein 1, resulting in increased eIF4E enrichment and HIF-2alpha translation. In addition, miR-558 promoted the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo, and these biological features were rescued by knockdown of AGO2, eIF4E, or HIF-2alpha. In clinical NB specimens, miR-558, AGO2, and eIF4E were highly expressed and positively correlated with HIF-2alpha expression. Patients with high miR-558, HIF 2alpha, AGO2, or eIF4E levels had lower survival probability. Taken together, these results demonstrate that miR-558 facilitates the expression of HIF-2alpha through bindingto its 5'-UTR, thus promoting the tumorigenesis and aggressiveness of NB. PMID- 27276679 TI - Upregulation of glycolysis and oxidative phosphorylation in benzo[alpha]pyrene and arsenic-induced rat lung epithelial transformed cells. AB - Arsenic and benzo[alpha]pyrene (B[a]P) are common contaminants in developing countries. Many studies have investigated the consequences of arsenic and/or B[a]P-induced cellular transformation, including altered metabolism. In the present study, we show that, in addition to elevated glycolysis, B[a]P/arsenic induced transformation also stimulates oxidative phosphorylation (OXPHOS). Proteomic data and immunoblot studies demonstrated that enzymatic activities, involved in both glycolysis and OXPHOS, are upregulated in the primary transformed rat lung epithelial cell (TLEC) culture, as well as in subcloned TLEC cell lines (TMCs), indicating that OXPHOS was active and still contributed to energy production. LEC expression, of the glycolytic enzyme phosphoglycerate mutase (PGAM) and the TCA cycle enzyme alpha-ketoglutarate dehydrogenase (OGDH), revealed an alternating cyclic pattern of glycolysis and OXPHOS during cell transformation. We also found that the expression levels of hypoxia-inducible factor-1a were consistent with the pattern of glycolysis during the course of transformation. Low doses of an ATP synthase inhibitor depleted endogenous ATP levels to a greater extent in TLECs, compared to parental LECs, indicating greater sensitivity of B[a]P/arsenic-transformed cells to ATP depletion. However, TLEC cells exhibited better survival under hypoxia, possibly due to further induction of anaerobic glycolysis. Collectively, our data indicate that B[a]P/arsenic-transformed cells can maintain energy production through upregulation of both glycolysis and OXPHOS. Selective inhibition of metabolic pathways may serve as a therapeutic option for cancer therapy. PMID- 27276680 TI - Increased serum levels of betatrophin in pancreatic cancer-associated diabetes. AB - Long-standing diabetes or glucose intolerance is recognized as a crucial event in the process of pancreatic cancer. Betatrophin, a novel liver-derived hormone, promotes beta-cell proliferation and improves glucose intolerance. However, the relationship between betatrophin and PDAC-associated diabetes is not fully understood. To evaluate the serum betatrophin levels in PDAC-associated diabetes, a total 105 Taiwanese subjects including 15 healthy subjects, and 12 patients having PDAC with normal glucose tolerance (PDAC-NGT), 12 patients having PC with impaired glucose tolerance (PDAC-IGT), and 66 patients having PC with diabetes mellitus (PDAC-DM) were enrolled for this study. Serum betatrophin and carbohydrate antigen 19-9 (CA19-9) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Compared to healthy subjects, PDAC patients had higher levels of betatrophin and CA19-9. Consistently, betatrophin protein was significantly expressed in pancreatic ductal of PDAC-associated DM patients using immunohistochemistry (IHC) method. Furthermore, multivariate regression analysis showed the betatrophin was significantly and positively independent with T category (beta= 0.605, P=0.010), serum albumin (beta= 0. 423, P=0.021), lipase (beta= 0.292, P=0.039), and blood urea nitrogen (BUN) (beta= 0.303, P=0.040). Further, the betatrophin was three folds of having PDAC-associated diabetes with the highest odds ratio [OR=3.39; 95% CI (1.20-9.57); P=0.021) and receiver operating characteristic (ROC) curve analysis showed that AUC value of betarophin was 0.853 which is slightly larger than AUC value of CA19-9 (0.792) in PDAC-DM patients. Interestingly, AUC value of betarophin plus CA19-9 was 0.988 in PDAC-DM patients. Therefore, betatrophin combined CA19-9 may serve as a potential biomarker for PDAC-associated diabetes. PMID- 27276681 TI - Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor. AB - Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) - the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. However, mechanisms that contribute to the agonist switch had not been fully clarified, and there were no therapies to block AR F877L. Using cell line models of castration-resistant prostate cancer (CRPC), we determined that cellular androgen content influences enzalutamide agonism of mutant F877L AR. Further, enzalutamide treatment of AR F877L-expressing cell lines recapitulated the effects of androgen activation of F877L AR or wild-type AR. Because the BET bromodomain inhibitor JQ-1 was previously shown to block androgen activation of wild-type AR, we tested JQ-1 in AR F877L-expressing CRPC models. We determined that JQ-1 suppressed androgen or enzalutamide activation of mutant F877L AR and suppressed growth of mutant F877L AR CRPC tumors in vivo, demonstrating a new strategy to treat tumors harboring this mutation. PMID- 27276682 TI - Presence of TMPRSS2-ERG is associated with alterations of the metabolic profile in human prostate cancer. AB - TMPRSS2-ERG has been proposed to be a prognostic marker for prostate cancer. The aim of this study was to identify changes in metabolism, genes and biochemical recurrence related to TMPRSS2-ERG by using an integrated approach, combining metabolomics, transcriptomics, histopathology and clinical data in a cohort of 129 human prostate samples (41 patients). Metabolic analyses revealed lower concentrations of citrate and spermine comparing ERGhigh to ERGlow samples, suggesting an increased cancer aggressiveness of ERGhigh compared to ERGlow. These results could be validated in a separate cohort, consisting of 40 samples (40 patients), and magnetic resonance spectroscopy imaging (MRSI) indicated an in vivo translational potential. Alterations of gene expression levels associated with key enzymes in the metabolism of citrate and polyamines were in consistence with the metabolic results. Furthermore, the metabolic alterations between ERGhigh and ERGlow were more pronounced in low Gleason samples than in high Gleason samples, suggesting it as a potential tool for risk stratification. However, no significant difference in biochemical recurrence was detected, although a trend towards significance was detected for low Gleason samples. Using an integrated approach, this study suggests TMPRSS2-ERG as a potential risk stratification tool for inclusion of active surveillance patients. PMID- 27276683 TI - Schlafen2 mutation unravels a role for chronic ER stress in the loss of T cell quiescence. AB - Immunologically naive lymphocytes are kept in a quiescent state until antigen engagement. These quiescent immune cells are characterized by small cell size, lack of spontaneous proliferation and low metabolic rate. Lymphocyte quiescence is actively enforced condition which ensures the preservation of proper differentiation and proliferation capabilities of naive and memory lymphocytes. Previously we described a chemically induced mutation in Schlafen2 (Slfn2), termed elektra, which breaks quiescence and compromises immunity. However, the mechanism by which Slfn2 maintains quiescence remains unknown. Here we demonstrate that elektra T cells display chronic ER stress under steady state conditions. Modulation of ER stress response by depletion of either UPR mediators XBP1 or CHOP, improved viability and partially corrected the developmental abnormalities and proliferation capabilities of elektra T cells. Altogether, our results demonstrate a functional connection between Slfn2 induced quiescence in T cells and ER homeostasis, clarifying a novel mechanism by which immune cell quiescence is maintained. PMID- 27276684 TI - MEF2C rs190982 polymorphism with late-onset Alzheimer's disease in Han Chinese: A replication study and meta-analyses. AB - The myocyte enhancer factor (MEF2) family of transcription factors plays a vital role in memory and learning due to its functions in regulating synapse number and reducing dendritic spines. Myocyte enhancer factor 2 C (MEF2C) is regarded as modulator of amyloid-protein precursor (APP) proteolytic processing, in which amyloid-beta (Abeta) is produced. A common single nucleotide polymorphism (SNP, rs190982) in MEF2C gene was identified to be related to late-onset Alzheimer's disease (LOAD) in Caucasians in a large meta-analysis of genome-wide association studies (GWAS). Here, we recruited unrelated 984 LOAD patients and 1348 healthy controls matched for gender and age to ascertain whether the rs190982 polymorphism is related to LOAD in Han Chinese. No difference in the genotype and allele distributions of the MEF2C rs190982 polymorphism was found between LOAD cases and healthy controls (genotype: P = 0.861; allele: P = 0.862), even after stratification for APOE epsilon4 allele as well as statistical adjustment for age, gender and APOE epsilon4 status. Furthermore, the meta-analysis in 4089 Chinese individuals did not detect the association of rs190982 within MEF2C with the risk for LOAD (OR = 1.03, 95%CI = 0.90-1.18). Overall, the current evidence did not support the relation between rs190982 polymorphism within MEF2C and the LOAD risk in Northern Han Chinese. PMID- 27276685 TI - Immunoglobulin G promotes skin graft acceptance in an immunologically potent rat model. AB - Immunoglobulin G (IgG) has been shown to protect graft rejection after transplantation, whereas the molecular mechanism of IgG in promoting graft acceptance has not been well established. In this study, we tested the effectiveness of IgG in preventing rejection of transplanted skin graft in an immunologically potent rat model, and studied the mechanism of this protection. We found that systemic or local administration of IgG significantly prolonged the survival of skin grafts with the immune tolerance induced by IgG and subcutaneous local injection of 1mg IgG to adult SD rat yielded the longest survival of skin grafts from 5.8 to 17.3 days. We also found that IgG reduced the number of pro inflammatory cells especially lymphocytes, neutrophils and basophils, increased the seral levels of anti-inflammatory factors including IL-10 and IL-4, and activated CD4+CD25+Foxp3+ regulatory T cells, unveiling the mechanisms of this protective effect. These findings provide new insight to support clinical application of IgG in treating transplantation. PMID- 27276686 TI - ATG4A promotes tumor metastasis by inducing the epithelial-mesenchymal transition and stem-like properties in gastric cells. AB - The metastasis of tumor cells to distant organs is an ominous feature of gastric cancer. However, the molecular mechanisms underlying the invasion and metastasis of gastric cancer cells remain elusive. In this study, we found that the expression of ATG4A, an autophagy-regulating molecule, was significantly increased in gastric cancer tissues and was significantlycorrelated with the gastric cancer differentiation degree, tumor invasion and lymph node metastasis. ATG4A over-expression significantly promoted gastric cancer cell migration and invasion in vitro and metastasis in vivo, as well as promoted gastric cancer cell stem-like properties and the epithelial-mesenchymal transition (EMT) phenotype. By contrast, ATG4A knockdown inhibited the migration, invasion and metastasis of cancer cells, as well as the stem-like properties and EMT phenotype. Mechanistically, ATG4A promotes gastric cancer cell stem-like properties and the EMT phenotype through the activation of Notch signaling not via autophagy, and using the Notch signaling inhibitor DAPT attenuated the effects of ATG4A on gastric cancer cells. Taken together, these findings demonstrated that ATG4A promotes the metastasis of gastric cancer cells via the Notch signaling pathway, which is an autophagy-independent mechanism. PMID- 27276687 TI - Assessing Social Isolation: Pilot Testing Different Methods. AB - Social isolation is a significant public health problem among many older adults; however, most of the empirical knowledge about isolation derives from community based samples. There has been less attention given to isolation in senior housing communities. The objectives of this pilot study were to test two methods to identify socially isolated residents in low-income senior housing and compare findings about the extent of isolation from these two methods. The first method, self-report by residents, included 47 out of 135 residents who completed in person interviews. To determine self-report isolation, residents completed the Lubben Social Network Scale 6 (LSNS-6). The second method involved a staff member who reported the extent of isolation on all 135 residents via an online survey. Results indicated that 26% of residents who were interviewed were deemed socially isolated by the LSNS-6. Staff members rated 12% of residents as having some or a lot of isolation. In comparing the two methods, staff members rated 2% of interviewed residents as having a lot of isolation. The combination of self report and staff report could be more informative than just self-report alone, particularly when participation rates are low. However, researchers should be aware of the potential discrepancy between these two methods. PMID- 27276688 TI - Second-Order Perturbation Theory for Generalized Active Space Self-Consistent Field Wave Functions. AB - A multireference second-order perturbation theory approach based on the generalized active space self-consistent-field (GASSCF) wave function is presented. Compared with the complete active space (CAS) and restricted active space (RAS) wave functions, GAS wave functions are more flexible and can employ larger active spaces and/or different truncations of the configuration interaction expansion. With GASSCF, one can explore chemical systems that are not affordable with either CASSCF or RASSCF. Perturbation theory to second order on top of GAS wave functions (GASPT2) has been implemented to recover the remaining electron correlation. The method has been benchmarked by computing the chromium dimer ground-state potential energy curve. These calculations show that GASPT2 gives results similar to CASPT2 even with a configuration interaction expansion much smaller than the corresponding CAS expansion. PMID- 27276690 TI - Exploring the urinary selenometabolome following a multi-phase selenite administration regimen in humans. AB - To gain more insight into the human metabolism of the essential trace element selenium, we investigate the response of the urinary selenium metabolites to changing selenium intake by applying a stepwise selenium administration regimen based on repeated dosaging. Sodium selenite was administered orally to healthy volunteers at an incrementally increasing dosage. The supplementation regimen extended over 20 days for each volunteer, and daily morning urine samples were collected prior to, during, and following the supplementation phases. A total of 160 urine samples were analyzed for total urinary selenium and a panel of selenometabolites by using ICPMS and HPLC/ICPMS. Selenosugar 1 gave the strongest response followed by TMSe and then selenosugar 3. Se-methylselenoneine excretion was not stimulated by increased selenium intake, suggesting that it is not in equilibrium with selenium body pools. Selenate was detected in all urine samples; it showed a clear and consistent response to supplementation and an abrupt return to baseline levels upon cessation of supplementation, indicating that it arose from the oxidation of the administered selenite rather than from the oxidation of endogenous hydrogen selenide. The gap between total urinary selenium and the sum of Se species markedly increased in response to selenium administration, which highlights the presence of unknown Se species that respond to selenite supplementation. The characterization of these unknown species and their possible biological activities might be essential before considering selenium supplementation in clinical trials. We discuss the implications of the responses of the selenium metabolites and their inter-relationships for selenium metabolism. PMID- 27276691 TI - New Experimental Insight into the Nature of Metal-Metal Bonds in Digallium Compounds: J Coupling between Quadrupolar Nuclei. AB - Multiple bonding between atoms is of ongoing fundamental and applied interest. Here, we report a multinuclear ((1) H, (13) C, and (71) Ga) solid-state magnetic resonance spectroscopic study of digallium compounds which have been proposed, albeit somewhat controversially, to contain single, double, and triple Ga-Ga bonds. Of particular relevance to the nature of these bonds, we have carried out two-dimensional (71) Ga J/D-resolved NMR experiments which provide a direct measurement of J((71) Ga,(71) Ga) spin-spin coupling constants across the gallium gallium bonds. When placed in the context of clear-cut experimental data for analogous singly, doubly, and triply bonded carbon spin pairs or boron spin pairs, the (71) Ga NMR data clearly support the notion of a different bonding paradigm in the gallium systems. Our findings are consistent with an increasing role across the purported gallane-gallene-gallyne series for classical and/or slipped pi-type bonding orbitals. PMID- 27276689 TI - mGlu1 receptor canonical signaling pathway contributes to the opening of the orphan GluD2 receptor. AB - The orphan Glutamate receptor Delta2 (GluD2) intrinsic ion channel activity is indirectly triggered by glutamate through stimulation of the metabotropic glutamate receptor 1 (mGlu1), in cerebellar Purkinje cells. However, the mechanisms of GluD2 ion channel opening are entirely unknown. In this work, we investigated the signaling pathways underlying the mGlu1-induced GluD2 current, performing whole-cell voltage-clamp recordings from mGlu1 and GluD2 transfected HEK293 cells. We show that the activation of GluD2 channels via DHPG-induced mGlu1 stimulation is Galphaq-dependent. Moreover, inhibition of the downstream components of the mGlu1 canonical signaling pathway PLC and PKC with U73122 and GF109203X, respectively, strongly reduced the DHPG-induced GluD2 current. These results were further confirmed on endogenous receptors at the Parallel Fiber - Purkinje Cell cerebellar synapse, indicating that the opening of the GluD2 channel by mGlu1 receptor mobilizes the canonical Gq-PLC-PKC pathway. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'. PMID- 27276693 TI - Highly Stable, Amide-Bridged Autoinducing Peptide Analogues that Strongly Inhibit the AgrC Quorum Sensing Receptor in Staphylococcus aureus. AB - Blocking quorum sensing (QS) pathways has attracted considerable interest as an approach to suppress virulence in bacterial pathogens. Toward this goal, we recently developed analogues of a native autoinducing peptide (AIP-III) signal that can inhibit AgrC-type QS receptors and attenuate virulence phenotypes in Staphylococcus aureus. Application of these compounds is limited, however, as they contain hydrolytically unstable thioester linkages and have only low aqueous solubilities. Herein, we report amide-linked AIP analogues with greatly enhanced hydrolytic stabilities and solubilities relative to our prior analogues, whilst maintaining strong potencies as AgrC receptor inhibitors in S. aureus. These compounds represent powerful tools for the study of QS. PMID- 27276694 TI - A framework for transitioning patients from pediatric to adult health settings for patients with neurogenic bladder. AB - BACKGROUND: Adolescents with neurogenic bladder are a vulnerable population that severely lacks consistent transitional care from pediatric to adult urology settings. AIMS: Our practice determined that 100 patients with spina bifida and other neurogenic bladder conditions were not appropriately transferred to the adult setting once reaching adulthood. METHODS: We initiated a transitional program to establish a dedicated and formal process for adolescent patients to transition to adult urology. The REACH clinic implements a formalized staging framework to facilitate migration of adolescents and young adults to the adult health setting. A social worker was incorporated to act as a patient advocate, behavioral health consultant, and resource specialist. RESULTS: To date 45 patients have been enrolled in the transition program. We have identified and categorized according to the appropriate stage. The REACH clinic has appropriately outlined the goals and mission of the program and resources utilized are financially practical and feasible by conducting a monthly combined clinic. The program has been instrumental in improving tracking and monitoring of these patients through their transition period. CONCLUSION: Through the efforts of the pediatric and adult urology teams, the REACH program is a dedicated framework that provides structure for transition of the adolescent patient. The addition of a social worker has resulted in enriched rapport and will likely result in improved compliance. This program allows for surveillance and evaluation of patient outcome indicators in this patient population. We believe that early introduction and frequent encounters with the adult urologic team is crucial to successful transitions. Neurourol. Urodynam. 36:973-978, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27276695 TI - Comment on the paper by Pitanguy. PMID- 27276696 TI - Comment on the article by Baum et al. PMID- 27276697 TI - [Nutritional status of elderly Brazilians: a multilevel approach]. AB - The objectives of this study were to diagnose the nutritional status of the elderly Brazilian population and to identify associated factors. The study used data from the Brazilian Household Budget Survey (2008/2009) for 20,114 elderly, whose nutritional status was assessed by body mass index (BMI). Associated factors were tested with the Pearson chi-square test and multilevel linear models. The hierarchical analysis showed a significant effect of state of Brazil on BMI variance (p-value = 0.001). The individual level showed a negative association (p-value < 0.001) with Asian-descendant race, male gender, living alone, and older age and a positive association with per capita income. Underweight was more prevalent among elderly in rural areas (26.3%) and in the Northeast (23.7%) and Central regions (20.9%), and obesity was more prevalent in the South (45.1%) and Southeast (38.3%) and in cities (39%). The study suggests the importance of further in-depth research on nutritional status of elderly based on contextual variables. PMID- 27276698 TI - Flexible Transparent Electronic Gas Sensors. AB - Flexible and transparent electronic gas sensors capable of real-time, sensitive, and selective analysis at room-temperature, have gained immense popularity in recent years for their potential to be integrated into various smart wearable electronics and display devices. Here, recent advances in flexible transparent sensors constructed from semiconducting oxides, carbon materials, conducting polymers, and their nanocomposites are presented. The sensing material selection, sensor device construction, and sensing mechanism of flexible transparent sensors are discussed in detail. The critical challenges and future development associated with flexible and transparent electronic gas sensors are presented. Smart wearable gas sensors are believed to have great potential in environmental monitoring and noninvasive health monitoring based on disease biomarkers in exhaled gas. PMID- 27276700 TI - MEND Syndrome: A Case Report with Scanning Electron Microscopy Findings of the Collodion Membrane. PMID- 27276699 TI - High-throughput screening and selection of mammalian cells for enhanced protein production. AB - The production of recombinant proteins for biotherapeutic use is a multibillion dollar industry, which has seen continual growth in recent years. In order to produce the best protein with minimal cost and time, selection methods are utilized during the cell line development process in order to select for the most desirable clonal cell line from a heterogeneous transfectant pool. Today, there is a vast array of potential selection methods available, which vary in cost, complexity and efficacy. This review aims to highlight cell line selection methods that exist for the isolation of high-producing clones, and also reviews techniques that can be used to predict, at a small scale, the performance of clones at large, industrially-relevant scales. PMID- 27276701 TI - Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes? AB - Growing epidemiological evidence suggests that nonalcoholic fatty liver disease (NAFLD) is an early predictor of and determinant for the development of type 2 diabetes and other features of the metabolic syndrome. This finding may have important clinical implications for the diagnosis, prevention and treatment of type 2 diabetes and its chronic complications. However, given the complex and bi directional relationships between NAFLD, insulin resistance and chronic hyperglycaemia, it is extremely difficult to distinguish whether NAFLD is a cause or a consequence of insulin resistance and type 2 diabetes. Indeed, at the molecular level, hepatic lipogenesis and hepatic glucose production depend on differentially regulated branches of the insulin signalling pathway. Furthermore, genetic studies suggest that excess hepatic fat is associated with progressive liver disease, but does not always increase the risk of incident type 2 diabetes. Here, we will briefly review the epidemiological, pathophysiological and molecular evidence linking NAFLD to the development of type 2 diabetes. We will also discuss some recent genetic and therapeutic advances that seem to challenge a causal role of NAFLD in the pathogenesis type 2 diabetes, and propose a working hypothesis to explain this apparent conundrum. In conclusion, progressive liver disease and type 2 diabetes are divergent though inter-related consequences of insulin resistance and the metabolic syndrome. PMID- 27276702 TI - A Case Of Neuroendocrine Carcinoma Expressing Myeloid Markers By Flow Cytometry And Review Of the Literature. AB - BACKGROUND: Flow cytometric data is often analyzed in isolation, without the benefit of clinical and morphologic context, and the findings must be interpreted with caution when unexpected results are obtained. METHODS: A bone marrow aspirate from a 69-year-old female with incidentally discovered pancytopenia was initially analyzed by flow cytometry alone. The results were subsequently correlated with clinical, morphologic, immunohistochemical, and cytogenetic findings. RESULTS: Morphology and immunohistochemistry confirmed metastatic small cell carcinoma; by flow cytometric analysis, the neoplastic cells were positive for CD56 and showed unexpected expression of CD13 and CD117, raising the possibility of a myeloid neoplasm. CONCLUSIONS: Flow cytometric markers are not entirely sensitive or specific, and aberrant expression or lack of expression of certain markers can complicate interpretation, particularly when this is done in isolation (i.e., in reference laboratories). Whenever possible, clinical and morphologic correlation is strongly recommended. (c) 2016 International Clinical Cytometry Society. PMID- 27276703 TI - An Alternative Narrative. PMID- 27276704 TI - Modulation of macrophage polarization and lung cancer cell stemness by MUC1 and development of a related small-molecule inhibitor pterostilbene. AB - Tumor-associated macrophages (TAMs) polarized to the M2 phenotype play key roles in tumor progression in different cancer types, including lung cancer. MUC1 expression in various types of cancer is an indicator of poorer prognosis. Elevated MUC1 expression has been reported in inflammatory lung macrophages and is associated with lung cancer development. Here, we investigated the role of M2 polarized TAMs (M2-TAMs) in the generation of lung cancer stem cells (LCSCs) and tested pterostilbene, a small-molecule agent that modulates MUC1 expression in lung cancer cells, with the goal of subverting the microenvironment toward a favorable anti-tumor impact. We found that MUC1 was overexpressed in lung cancer patients, which was associated with poor survival rates. M2-TAMs and cancer cell lines were co-cultured in an experimental tumor microenvironment model. The expression levels of MUC1 and cancer stemness genes significantly increased in lung cancer cells in the presence of the M2-TAM cells. Intriguingly, pterostilbene dose-dependently suppressed self-renewal ability in M2-TAMs-co cultured lung cancer cells, and this suppression was accompanied by downregulation of MUC1, NF-kappaB, CD133, beta-catenin, and Sox2 expression. Moreover, MUC1-silenced M2-TAMs exhibited a significantly lower ability to promote LCSC generation and decreased levels of NF-kappaB, CD133, and Sox2. The results suggest that MUC1 plays an important role in TAM-induced LCSC progression. Pterostilbene may have therapeutic potential for modulating the unfavorable effects of TAMs in lung cancer progression. PMID- 27276705 TI - 5d, a novel analogue of 3-n-butylphthalide, decreases NADPH oxidase activity through the positive regulation of CK2 after ischemia/reperfusion injury. AB - 5d, a novel analogue of the racemic 3-n-butylphthalide (NBP), has been reported for its free radical scavenging activity in vitro and preventive neuroprotection in vivo. Nevertheless, the mechanism by which 5d attenuated ischemia/reperfusion (I/R) injury is still unknown. Our results showed that 5d significantly increased CK2 activity as well as CK2alpha and 2alpha' protein levels after I/R injury. Besides, 5d suppressed the translocation of cytosolic p47phox and Rac1 to the membrane, decreased NOX4 expression and ROS generation. Furthermore, 5d blocked the dissociation between CK2alpha and Rac1 so as to decrease NADPH oxidase activity. Based on these findings, we propose that the neuroprotective effect of 5d is due to an increase of CK2 activity, which blocks I/R-induced dissociation between CK2alpha and Rac1, decreases NADPH oxidase activity, inhibits ROS production and finally realizes the neuroprotection of I/R. These findings point to that 5d might be considered an attractive candidate for further studies in ischemic stroke. PMID- 27276706 TI - Outcomes of re-treatment with first-line trastuzumab plus a taxane in HER2 positive metastatic breast cancer patients after (neo)adjuvant trastuzumab: A prospective multicenter study. AB - Trastuzumab is the backbone of HER2-positive early breast cancer (eBC) and metastatic breast cancer (mBC) treatment, but limited data exist as to re treatment in relapsed patients. In this prospective, single arm, multicenter trial, we assessed efficacy and safety of trastuzumab and taxane combination in Chinese patients with HER2-positive mBC relapsed after prior (neo)adjuvant trastuzumab. Patients with previous (neo)adjuvant trastuzumab treatment for>=9 weeks and a relapse-free interval >=6 months were assigned to trastuzumab treatment with paclitaxel or docetaxel. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), time to progression (TTP), overall survival (OS) and safety profile. Thirty-two patients were enrolled and treated for a median duration of 33.5 weeks. The median PFS was 9.9 months (95% CI, 6.28 - 13.63 months). The ORR was 81.3% (95% CI, 63.6% - 92.8%) and CBR (CR+PR+SD>=6months) was 81.3% (95% CI, 63.6% - 92.8%). The median DOR was 9.8 months (95% CI, 5.82 - 11.60 months) and median TTP was 9.9 months (95% CI, 6.28-13.63 months). OS median follow-up time was 20.1 months and 25% OS time was 25.5 months. The safety profile was acceptable with common adverse events including leukopenia (59.4%), neutropenia (56.3%), hypoaesthesia (34.4%) and granulocytopenia (31.3%). In conclusion, re-treatment with trastuzumab plus a taxane as first-line therapy is an effective regimen for patients with HER2 positive mBC relapsed after (neo)adjuvant trastuzumab. The safety profile was good and the adverse reactions were tolerable and manageable. PMID- 27276707 TI - Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses. AB - Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Prognosis is particularly poor for relapses occurring less than one year after the end of first-line treatment (early relapses/ER) compared to those occurring more than one year after (late relapses/LR). To better understand genomic alterations underlying the delay of relapse, we identified copy number variations (CNVs) on 39 tumor samples from a homogeneous series of patients included in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) prospective study. To identify CNVs associated with ER or LR, we devised an original method based on Significance Analysis of Microarrays, a permutation based method which allows control of false positives due to multiple testing. Deletions of CDKN2A/B (28%) and IBTK (23%) were frequent events in relapsed DLBCLs. We identified 56 protein-coding genes and 25 long non-coding RNAs with significantly differential CNVs distribution between ER and LR DLBCLs, with a false discovery rate < 0.05. In ER DLBCLs, CNVs were related to transcription regulation, cell cycle and apoptosis, with duplications of histone H1T (31%), deletions of DIABLO (26%), PTMS (21%) and CK2B (15%). In LR DLBCLs, CNVs were related to immune response, with deletions of B2M (20%) and CD58 (10%), cell proliferation regulation, with duplications of HES1 (25%) and DVL3 (20%), and transcription regulation, with MTERF4 deletions (20%). This study provides new insights into the genetic aberrations in relapsed DLBCLs and suggest pathway targeted therapies in ER and LR DLBCLs. PMID- 27276708 TI - Besides an ITIM/SHP-1-dependent pathway, CD22 collaborates with Grb2 and plasma membrane calcium-ATPase in an ITIM/SHP-1-independent pathway of attenuation of Ca2+i signal in B cells. AB - CD22 is a surface immunoglobulin implicated in negative regulation of B cell receptor (BCR) signaling; particularly inhibiting intracellular Ca2+ (Ca2+i)signals. Its cytoplasmic tail contains six tyrosine residues (Y773/Y783/Y817/Y828/Y843/Y863, designated Y1~Y6 respectively), including three (Y2/5/6) lying within immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that serve to recruit the protein tyrosine phosphatase SHP-1 after BCR activation induced phosphorylation. The mechanism of inhibiting Ca2+i by CD22 has been poorly understood. Previous study demonstrated that CD22 associated with plasma membrane calcium-ATPase (PMCA) and enhanced its activity (Chen, J. et al. Nat Immunol 2004;5:651-7). The association is dependent on BCR activation-induced cytoplasmic tyrosine phosphorylation, because CD22 with either all six tyrosines mutated to phenylalanines or cytoplasmic tail truncated loses its ability to associate with PMCA. However, which individual or a group of tyrosine residues determine the association and how CD22 and PMCA interacts, are still unclear. In this study, by using a series of CD22 tyrosine mutants, we found that ITIM Y2/5/6 accounts for 34.3~37.1% Ca2+i inhibition but is irrelevant for CD22/PMCA association. Non-ITIM Y4 and its YEND motif contribute to the remaining 69.4~71.7% Ca2+i inhibition and is the binding site for PMCA-associated Grb2. Grb2, independently of BCR cross-linking, is constitutively associated with and directly binds to PMCA in both chicken and human B cells. Knockout of Grb2 by CRISPR/Cas9 completely disrupted the CD22/PMCA association. Thus, our results demonstrate for the first time that in addition to previously-identified ITIM/SHP 1-dependent pathway, CD22 holds a major pathway of negative regulation of Ca2+i signal, which is ITIM/SHP-1-independent, but Y4/Grb2/PMCA-dependent. PMID- 27276709 TI - Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration. AB - Recent studies have identified biomarkers of chronological age based on DNA methylation levels. Since active smoking contributes to a wide spectrum of aging related diseases in adults, this study intended to examine whether active smoking exposure could accelerate the DNA methylation age in forms of age acceleration (AA, residuals of the DNA methylation age estimate regressed on chronological age). We obtained the DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation450 Beadchip array in two independent subsamples of the ESTHER study and calculated their DNA methylation ages by two recently proposed algorithms. None of the self-reported smoking indicators (smoking status, cumulative exposure and smoking cessation time) or serum cotinine levels was significantly associated with AA. On the contrary, we successfully confirmed that 66 out of 150 smoking-related CpG sites were associated with AA, even after correction for multiple testing (FDR <0.05). We further built a smoking index (SI) based on these loci and demonstrated a monotonic dose-response relationship of this index with AA. In conclusion, DNA methylation-based biological indicators for current and past smoking exposure, but not self-reported smoking information or serum cotinine levels, were found to be related to DNA methylation defined AA. Further research should address potential mechanisms underlying the observed patterns, such as potential reflections of susceptibility to environmental hazards in both smoking related methylation changes and methylation defined AA. PMID- 27276711 TI - FOXC2 disease-mutations identified in lymphedema-distichiasis patients cause both loss and gain of protein function. AB - Dominant mutations in the FOXC2 gene cause a form of lymphedema primarily of the limbs that usually develops at or after puberty. In 90-95% of patients, lymphedema is accompanied by distichiasis. FOXC2 is a member of the forkhead/winged-helix family of transcription factors and plays essential roles in different developmental pathways and physiological processes. We previously described six unrelated families with primary lymphedema-distichiasis in which patients showed different FOXC2 mutations located outside of the forkhead domain. Of those, four were missense mutations, one a frameshift mutation, and the last a stop mutation. To assess their pathogenic potential, we have now examined the subcellular localization and the transactivation activity of the mutated FOXC2 proteins. All six FOXC2 mutant proteins were able to localize into the nucleus; however, the frameshift truncated protein appeared to be sequestered into nuclear aggregates. A reduction in the ability to activate FOXC1/FOXC2 response elements was detected in 50% of mutations, while the remaining ones caused an increase of protein transactivation activity. Our data reveal that either a complete loss or a significant gain of FOXC2 function can cause a perturbation of lymphatic vessel formation leading to lymphedema. PMID- 27276712 TI - 4,4'-diaponeurosporene, a C30 carotenoid, effectively activates dendritic cells via CD36 and NF-kappaB signaling in a ROS independent manner. AB - Carotenoids could be divided into C30 carotenoids and C40 carotenoids. The immune functions of C40 carotenoids had been extensively researched, while those of C30 carotenoids still remain unclear. In this study, the immune functions of a biosynthetic C30 carotenoid, 4,4'-diaponeurosporene (Dia), were identified on dendritic cells (DCs). DCs treated with 1 MUM Dia for 24 h showed morphologic and phenotypic characteristics of mature state and had an increased production of IL 6, IL-10, IL-12p70 and TNFalpha, while beta-carotene had a suppressive effect on DCs maturation. Moreover, Dia promoted antigen uptake of DCs in vitro and increased the quantity of antigen loaded DCs in mesenteric lymph nodes (MLN). Dia treated DCs also had an enhanced ability to stimulate T cell proliferation and Th1 polarization. Further researches showed that Dia activated DCs via CD36 as well as ERK, JNK, and NF-kappaB signals in a reactive oxygen species (ROS) independent manner. PMID- 27276710 TI - Important molecular genetic markers of colorectal cancer. AB - Colorectal cancer (CRC) ranks third in the incidences of cancer morbidity and mortality worldwide. CRC is rather heterogeneous with regard to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers is used for molecular subtype determination, prognosis, and estimation of sensitivity to different drugs in practice. These biomarkers can include germline and somatic mutations, chromosomal aberrations, genomic abnormalities, gene expression alterations at mRNA or protein level and changes in DNA methylation status. In the present review we discuss the most important and well-studied CRC biomarkers, and their potential clinical significance and current approaches to molecular classification of colorectal tumors. PMID- 27276713 TI - Tumor specific mutations in TERT promoter and CTNNB1 gene in hepatitis B and hepatitis C related hepatocellular carcinoma. AB - Recurrent somatic mutations in the promoter region of telomerase reverse transcriptase (TERT) gene and in the exon 3 of CTNNB1 gene have been recognized as common events in hepatocellular carcinoma (HCC) with variable frequencies depending on etiology and geographical region. We have analyzed TERT promoter and CTNNB1 gene mutations in 122 cases of hepatitis B (HBV) and hepatitis C (HCV) related HCCs, in 7 cases of cholangiocarcinoma (CC) and hepatocholangiocarcinoma (HCC-CC) as well as in autologous cirrhotic tissues. Overall, 50.4% and 26% of HCC as well as 14.3% and none of CC and HCC-CC were mutated in TERT promoter and in CTNNB1 exon 3, respectively. TERT and CTNNB1 mutations were found more frequently in HCV related (53.6% and 26.4%, respectively) than HBV related (41.7% and 16.7%, respectively) HCCs and coexisted in 57.6% of CTNNB1 mutated tumors. Mutations in TERT and CTNNB1 were not associated with the functional promoter polymorphism rs2853669. No mutations were detected in the 129 non-HCC cirrhotic tissues. In conclusion, mutations in TERT promoter and in CTNNB1 gene represent specific cancer signatures in the pathogenesis of viral related HCC and could be promising early biomarkers as well as targets for tailored therapies. PMID- 27276714 TI - SSX2 regulates focal adhesion but does not drive the epithelial to mesenchymal transition in prostate cancer. AB - Prostate cancer is the most commonly diagnosed malignancy for men in the United States. Metastatic prostate cancer, the lethal form of the disease, has a life expectancy of approximately five years. Identification of factors associated with this transition to metastatic disease is crucial for future therapies. One such factor is the SSX gene family, a family of cancer/testis antigens (CTA) transcription factors which have been shown to be aberrantly expressed in other cancers and associated with the epithelial to mesenchymal transition (EMT). We have previously shown that SSX expression in prostate cancers was restricted to metastatic tissue and not primary tumors. In this study, we have identified SSX2 as the predominant SSX family member expressed in prostate cancer, and found its expression in the peripheral blood of 19 of 54 (35%) prostate cancer patients, with expression restricted to circulating tumor cells, and in 7 of 15 (47%) metastatic cDNA samples. Further, we examined SSX2 function in prostate cancer through knockdown and overexpression in prostate cancer cell lines. While overexpression had little effect on morphology or gene transcript changes, knockdown of SSX2 resulted in an epithelial morphology, increased cell proliferation, increased expression of genes involved in focal adhesion, decreased anchorage independent growth, increased invasion, and increased tumorigenicity in vivo. We conclude from these findings that SSX2 expression in prostate cancer is not a driver of EMT, but is involved in processes associated with EMT including loss of focal adhesion that may be related to tumor cell dissemination. PMID- 27276716 TI - In thematic volumes of The Alkaloids seminal developments in areas of exceptional interest are summarized. PMID- 27276717 TI - "Nothing About Us Without Us": Toward Patient- and Family-Centered Care. PMID- 27276718 TI - [Not Available]. PMID- 27276715 TI - Emerging roles and underlying molecular mechanisms of DNAJB6 in cancer. AB - DNAJB6 also known as mammalian relative of DnaJ (MRJ) encodes a highly conserved member of the DnaJ/Hsp40 family of co-chaperone proteins that function with Hsp70 chaperones. DNAJB6 is widely expressed in all tissues, with higher expression levels detected in the brain. DNAJB6 is involved in diverse cellular functions ranging from murine placental development, reducing the formation and toxicity of mis-folded protein aggregates, to self-renewal of neural stem cells. Involvement of DNAJB6 is implicated in multiple pathologies such as Huntington's disease, Parkinson's diseases, limb-girdle muscular dystrophy, cardiomyocyte hypertrophy and cancer. This review summarizes the important involvement of the spliced isoforms of DNAJB6 in various pathologies with a specific focus on the emerging roles of human DNAJB6 in cancer and the underlying molecular mechanisms. PMID- 27276719 TI - [Age-related cognitive impairment: conceptual changes and diagnostic strategies]. AB - The actual field of dementia encompasses also the pre-symptomatic phase, which may evolve for decades. Early detection and appropriate diagnosis decrease patient's and family's anxiety, improve patient's global care and allow better legal patient's protection. General Practitioners have at hand several available tools to screen a neurocognitive disorder, with up to 80% of sensitivity and specificity, to complete their clinical evaluation. An accurate diagnosis requires then a complete medical, neurological neuropsychological and neuroradiological evaluation in a Memory Clinic. Other investigations, such as functional cerebral imagery and spinal tap can be critical in unusual situations. Despite mood improvement after diagnostic announcement, increased suicidal risk in the 3 first months should be screened. PMID- 27276720 TI - [Dementia with motor and language disorders]. AB - Memory is not the only core diagnostic criteria in Alzheimer's disease and many dementias are characterized by other cognitive deficits. Moreover dementias are often associated with multiple and complex motor signs. The first part of this reviewcovers parkinsonism in diffuse Lewy Body Disease and other neurodegenerative diseases, corticobasal syndrome, or motor deficit in the motoneurone disease-frontotemporal dementia spectrum. In the second part, primary progressive aphasia and its three variants including basic clinical evaluation are described. These complex clinical syndromes involving motor and language systems are important for the clinical practice since they are part of diagnostic criteria of several neurodegenerative diseases and can be considered as phenotypical markers of neurodegeneration. PMID- 27276721 TI - [Behavorial and psychological symptoms in dementia: what alternative to drug?]. AB - Behavioral and psychological symptoms of dementia (BPSD) are frequent and represent a challenge for an optimal care of patients. They must be investigated systematically and if necessary analyzed with specialized teams in the domain of old age Psychiatry so that these disorders are optimally addressed and complications are prevented. A precise analysis of potential causes of BPSD in concertation with both family members and caring team allows clinicians to avoid the use of drugs that may appear to solve the immediate issue but happen to have serious side effects or even toxicity over time. PMID- 27276722 TI - [Cerebrospinal fluid biomarkers of Alzheimer's disease in current clinical practice]. AB - The cerebrospinal fluid levels of amyloid beta 1-42 (Abeta1-42), total tau and tau phosphorylated at threonine 181 (ptau181) are well established biomarkers of cerebral amyloid pathology and tau related neurodegeneration, two hallmarks of Alzheimer's disease. These biomarkers can help to improve diagnostic accuracy and consequent decisions on counseling, support, and therapy of patients with mild cognitive impairment and dementia. The use of biomarkers is part of the proposed new criteria of AD diagnosis. It may be particularly helpful in cases of atypical clinical presentation and uncertain diagnosis, and if an important benefit for the patient is expected. The ongoing development of new biomarkers based on less or non-invasive procedures will allow for a larger use of biomarkers to improve the diagnosis of cognitive impairment. PMID- 27276723 TI - [Brain imaging of Alzheimer' disease: state of the art and perspectives for clinicians]. AB - To improve the clinical detection of Alzheimer's disease (AD) new diagnostic criteria have been proposed, based on biomarkers of synaptic dysfunction, AD related neurodegeneration, and Abeta cerebral amyloidosis. Magnetic resonance imaging (MRI) and position emission tomography (PET) neuroimaging can be configured as powerful means for the detection of medial-temporal atrophy, reduced uptake of 18F-FDG PET or and increased retention of Abeta amyloid protein by amyloid-PET. In this review, we will discuss these promising techniques that allow assessing in vivo AD pathology and help clinicians to better diagnose and follow-up patients, particularly in clinical trials using disease-modifying treatments. PMID- 27276724 TI - [Dementia: management and prevention]. AB - Dementia represents a great challenge for health care providers. Detection of cognitive impairment is critical for early diagnosis of dementia. Early diagnosis allows to initiate individualized management that focuses on maintaining patient's autonomy and supporting their caregivers. Proposed multimodal interventions include physical activity, cognitive training, mediterranean diet, and management of cardiovascular risk factors. Before the initiation of pro cognitive therapy, medication review is essential to evaluate current treament and determine specific therapeutic objectives, based on patient's overall health and preferences. Overall risk reduction for dementia revolves around similar measures that target physical activity, cognition, diet and management of cardiovascular risk factors. PMID- 27276725 TI - [Iodine excess induced thyroid dysfunction]. AB - The principle sources of iodine overload, amiodarone and radiologic contrast media, are frequently used in modern medicine. The thyroid gland exerts a protective effect against iodine excess by suppressing iodine internalization into the thyrocyte and iodine organification, the Wolff-Chaikoff effect. Insufficiency of this effect or lack of escape from it leads to hypo- or hyperthyroidism respectively. Amiodarone induced thyrotoxicosis is a complex condition marked by two different pathophysiological mechanisms with different treatments. Thyroid metabolism changes after exposure to radiologic contrast media are frequent, but they rarely need to be treated. High risk individuals need to be identifed in order to delay the exam or to monitor thyroid function or apply prophylactic measures in selected cases. PMID- 27276726 TI - [Not Available]. PMID- 27276727 TI - [Not Available]. PMID- 27276728 TI - [Not Available]. PMID- 27276729 TI - [Not Available]. PMID- 27276730 TI - [Not Available]. PMID- 27276731 TI - [Not Available]. PMID- 27276732 TI - [Not Available]. PMID- 27276733 TI - [Not Available]. PMID- 27276734 TI - The Optimal Cut-Points for Weight and Non-Weight Quantitative Ultrasound of the Calcaneus to Screen Osteoporosis in Postmenopausal Women. AB - OBJECTIVE: To determine the optimal cut-off point of quantitative ultrasound (QUS) of the calcaneus, and optimized position for QUS of the calcaneus, between non-weight (sitting) and weight (standing) position, to screen osteoporosis in postmenopausal women. MATERIAL AND METHOD: A cross-sectional study of postmenopausal women aged 65 years or older who came for bone mineral density (BMD) evaluation at the menopause unit, Department of Obstetrics and Gynecology, Ramathibodi Hospital between April 2013 and October 2015. Bone tissue was measured by using QUS of the calcaneus in the standard sitting (non-weight position) and in standing (weight position) consecutively of non-dominant calcaneus to compared with BMD that measured by dual energy X-ray absorptiometry (DXA) of lumbar spine and hip within the same visit of QUS measurement. The area under Receiver Operating Characteristic (ROC) curve and optimal of diagnostic properties to diagnosed osteoporosis were analyzed by sensitivity, specificity, positive and negative likelihood ratio (LR +/-). RESULTS: One hundred sixty one postmenopausal women were enrolled, median age was 70 (65, 94) years old, median time since menopause was 22 (10, 55) years. Ten point five percent of subjects had history of osteoporotic fracture at wrist. The prevalence of osteoporosis was 23% at lumbar spine and 30% at femoral neck respectively. Area under ROC curve for diagnosed osteoporosis was 0.73 in the non-weight QUS of the calcaneus and correlated well with using DXA at neck of femur (gold standard). However the weight or standing position did not improve the diagnostic power of QUS of the calcaneus. The optimal cut-point value of QUS of the calcaneus to screen osteoporosis at stiffness index was determined by T-score of <= -2.6 with 81.42%, 45.83%, 1.5, and 0.41 for the sensitivity, specificity, LR +/- respectively. CONCLUSION: QUS of the calcaneus was acceptable and promising to be alternative tool for screening osteoporosis in postmenopausal woman age older than 65 years by the optimal cut-point of stiffness index T-score at <= -2.6 measured in standard position or non-weight method. PMID- 27276735 TI - Clinical Characteristics of Histoplasmosis in Siriraj Hospital. AB - BACKGROUND: Histoplasmosis is a rare infectious disease caused by Histoplasmosis capsulatum (H. capsulatum), a dimorphic fungus. Histoplasmosis is not endemic to Thailand. Cases of histoplasmosis are sporadic and mostly associated with HIV disease. Clinical characteristics and treatment outcomes of histoplasmosis in Thai patients have not been well described. OBJECTIVE: To investigate the clinical characteristics and outcomes of patients with histoplasmosis at Siriraj Hospital in Bangkok, Thailand MATERIAL AND METHOD: This retrospective investigation studied adult patients with histoplasmosis who attended Siriraj Hospital for treatment between 2002 and 2012 (11 years). Clinical characteristics, microbiological data, and treatment outcomes were analyzed. RESULTS: Fifty-seven patients were included in the study. Twenty-one (37%) were culture-proven, 37 (64.9%) were male, and mean age was 37 years. Fifty-four (95%) patients had co-morbid diseases, of which HIV infection was the most common (85%), followed by autoimmune diseases. Mean CD4 count among HIV-infected patients was 40 (range: 1-320) cells/mm3. The most common clinical syndrome of histoplasmosis was progressive disseminated histoplasmosis (PDH) (86%), followed by chronic non-cavitary histoplasmosis (7%), and fungal synovitis (5%). Organ involvement included lungs (38%), oral cavity (4%), adrenal gland (2%), and heart valve (2%). Bone and joint infection was found in three patients, all of which were HIV-negative. Common clinical manifestations were fever (84%), weight loss (88%), anemia (63%), jaundice (16%), hepatomegaly (38%), splenomegaly (18%), lymphadenopathy (41%), and molluscum-like skin lesions (30%). Chest radiography was abnormal in 54% of patients, with 65% of those having bilateral pulmonary lesions. Interstitial infiltration was the most common radiographic finding (42%), followed by perihilar adenopathy (19%) and cavitary lesion (16%). Microscopic examination was positive for yeast-like organism in bone marrow and skin in 66% and 89% of patients, respectively. Budding yeasts were detected in all biopsied tissues obtained from oral lesions, synovium, and adrenal gland. Fungal cultures were positive from bone marrow, skin, and blood in 20%, 17%, and 5% of patients, respectively. All adrenal glands and heart valve vegetations sent for culture were positive. Fifty-one patients received amphotericin B deoxycholate followed by itraconazole, with clinical cure achieved in 86%. Survival rates at 6- and 12-month were 88% and 75%, respectively. CONCLUSION: PDH is the most common syndrome of histoplasmosis in Siriraj Hospital. Skin and bone marrow study are the most useful investigations for diagnosis. Effective treatment includes amphotericin B, followed by oral itraconazole. PMID- 27276736 TI - Clinical Significance of Bone Marrow Involvement as Confirmed by Bone Marrow Aspiration vs. Bone Marrow Biopsy in Diffuse Large B-cell Lymphoma. AB - BACKGROUND: In diffuse large B-cell lymphoma (DLBCL), bone marrow (BM) involvement confirmed by BM biopsy confers a poor prognosis. However, in clinical practice, there may be disagreement in results between BM biopsy and BM aspiration in determination of BM involvement. It is unknown which of BM biopsy or BM aspiration better correlates with clinical outcome. OBJECTIVE: To evaluate clinical outcome of BM involvement as confirmed by BM aspiration vs. confirmation by BM biopsy in patients with DLBCL. MATERIAL AND METHOD: Clinical data, treatment, and outcome of 126 DLBCL patients with available BM aspirate slides who attended the Hematology Clinic at Siriraj Hospital between January 1, 2007 and December 31, 2009 were reviewed. BM aspirate slides were revised and interpreted by hematologists. RESULTS: BM involvement was found in 12.7% (16/126) by BM biopsy and 24.6% (31/126) by BM aspiration. Regarding BM biopsy results, rates of complete remission (CR) among patients with unequivocal involvement, equivocal involvement, and without involvement were 75.0%, 57.1%, and 77.7%, respectively (p = 0.464). Two-year overall survival (OS) rates among the three groups were not significantly different (p = 0.663). Regarding BM aspiration results, CR rates among patients with unequivocal involvement, equivocal involvement, and without involvement were 80.6%, 75.8%, and 72.7% (p = 0.755). Two-year OS rates among the three groups were not significantly different (p = 0.118). In multivariate analysis, BM involvement as determined by either BM biopsy or BM aspiration was not associated with CR rate or 2-year OS rates. However, the International Prognostic Index (PI) and use of rituximab were found to be signifcantly associated with CR rate and OS. CONCLUSION: In patients with DLBCL, BM involvement confirmed by either BM biopsy or BM aspiration appears not to influence the rate of complete remission or 2-year overall survival. PMID- 27276737 TI - Epidemiology of Antibiotic Use and Antimicrobial Resistance in Selected Communities in Thailand. AB - OBJECTIVE: To generate epidemiological information regarding antibiotic use and antimicrobial resistance (AMR) in targeted communities for use by the Thailand AMR Containment and Prevention Program. MATERIAL AND METHOD: A survey of antibiotics sold by 215 grocery stores and retail shops located in the target communities was done by the local people who were instructed to purchase specified antibiotics and to present to such stores and shops with symptoms of sore throat, backache, common cold, acute diarrhea, inflamed uterus, and dysuria. The purchased drugs were then identified and recorded. Contamination of extended spectrum beta-lactamase (ESBL)-producing E. coli was identified in 174 samples of foods and open water sources collected from the target communities. Carriage of ESBL-producing E. coli in gastrointestinal tracts of 534 adults living in the target communities was performed by stool sample culture. One thousand three hundred one patients with upper respiratory infection (URI) and 235 patients with acute diarrhea who attended the tambon health promoting hospitals located in the target communities were monitored for their clinical outcomes of treatments. The patients with URI and acute diarrhea with no indication of antibiotic received symptomatic treatments as appropriate and they were followed via telephone contact every few days until all symptoms related to URI and acute diarrhea disappeared. The data were analyzed by descriptive statistics. RESULTS: Antibiotics were sold to the local people who were presenting with common ailments at many grocery stores and retail shops in their respective communities. In almost all cases, antibiotics were inappropriately given. Overall prevalence of ESBL-producing E. coli contamination in foods and open water sources was 26.4%. ESBL-producing E. coli was isolated from fresh meat and open water sources in many samples. Overall prevalence of ESBL-producing E. coli carriage in gastrointestinal tracts of the adults cultured was 66.5%. All patients with URI and acute diarrhea who had no indication of antibiotics and did not receive antibiotics had either cure or favorable response within seven days of start of symptomatic treatment. CONCLUSION: Antibiotics are widely available and are inappropriately sold and given by grocery stores and retail shops located within local communities in Thailand. Antibiotic-resistant bacteria commonly and freely circulate within the community. Patients with URI and acute diarrhea with no indication for antibiotic therapy can be treated without antibiotics. Findings and observations from this study will be used as part of a social marketing campaign on prevention and containment of AMR to educate people living within communities in Thailand. PMID- 27276738 TI - Impact of GLI-2012 Spirometric References and Lower Limit of Normal on Prevalence of COPD in Older Urban Thai Persons. AB - BACKGROUND: Previous analysis of survey data from a study in older urban Thai persons reported prevalence of chronic obstructive pulmonary disease (COPD) of 7.11% according to formerly recommended criteria that used fixed ratio (70%) of pre-bronchodilator FEV1/FVC as the cut-off value. In 2012, the Global Lung Initiative (GLI)-2012 equations for spirometric reference were established and the diagnostic criteria for COPD were changed. OBJECTIVE: To reanalyze the data collected during the 2002 respiratory health survey to determine prevalence of COPD in older urban Thai persons according to the new GLI-2012 equations. MATERIAL AND METHOD: Demographic and clinical data of 3,094 subjects aged >= 60 years from 124 urban communities were re-analyzed. Prevalence of COPD determined by post-bronchodilator FEV1/FVC and GLI-2012 equations using lower limit of normal by the Lambda-Mu-Sigma method (LMS-LLN) was compared to COPD prevalence findings based on criteria used in previous analysis. RESULTS: Prevalence of COPD in the study population using post-bronchodilator FEV1/FVC and LMS-LLN was 6.50% (95% CI: 5.63-7.3 7), compared with 7.82% (95% CI: 6.87-8.77) when fixed ratio (70%) of FEV1/FVC was used as cut-off. Diagnostic agreement of COPD between LMS LLN and fixed ratio was high (kappa 0.88, p < 0.0001). However 45/242 (18.6%) subjects diagnosed as COPD by fixed ratio criteria were considered as "over diagnosed" when LMS-LLN was used as the standard cut-off The same comparison applied to subjects aged 80 years revealed an increased rate of over-diagnosis to 7/22 (31.8%) subjects. Higher agreement was observed (kappa 0.95, p < 0.0001) when comparing between cut-offs for diagnosis of "at least GOLD stage II" COPD. CONCLUSION: Prevalence of COPD in older urban Thai persons was lower when LMS-LLN was substituted for fixed ratio (70%) of FEV1/FVC. Agreement in COPD diagnosis between both criteria was high, but a substantial proportion of subjects may be over-diagnosed PMID- 27276739 TI - Impact of Isomaltulose and Sucrose Based Breakfasts on Postprandial Substrate Oxidation and Glycemic/Insulinemic Changes in Type-2 Diabetes Mellitus Subjects. AB - OBJECTIVE: To investigate the effect of isomaltulose (ISO) and sucrose (SUC) based breakfast on the postprandial substrate oxidation and glycemic/insulinemic changes in type 2 diabetes mellitus subjects (T2DM). MATERIAL AND METHOD: This was a randomized, controlled, double blind, and crossover study performed in two to five days. About 10 to 12 hours prior to the test, the subjects were not allowed to consume food or drink other than water. On the experimental day pre- and postprandial plasma glucose, serum insulin, and substrate utilization were measured after the subjects consumed a test breakfast with ISO or SUC, followed by a standard lunch three hours later. RESULTS: The plasma glucose levels in subjects after consuming ISO breakfast tended to be lower than subjects consuming SUC breakfast at 30- and 60-minute, respectively. The second meal effect after standard lunch (240-minute) on insulin levels in subject consuming ISO breakfast tended to be lower than that of subjects consuming SUC breakfast. Substrate oxidation indicated that the incremental area under the fat oxidation of ISO breakfast was 20% higher comparing to SUC breakfast. CONCLUSION: Therefore, ISO based breakfast tends to provide less postprandial glucose and insulin levels than SUC based breakfast, thereby increasing postprandial fat oxidation. PMID- 27276740 TI - Lupus Damage and Waist Circumference as the Independent Risk Factors for Cardiovascular Disease in SLE Patients from Phramongkutklao Hospital. AB - BACKGROUND: Cardiovascular disease (CVD) has been reported to be a major cause of both morbidity and premature mortality in systemic lupus erythematosus (SLE) patients. OBJECTIVE: To determine the prevalence of cardiovascular disease and associated risk factors in Thai SLE patients from Phramongkutklao Hospital, Thailand. MATERIAL AND METHOD: A retrospective cross-sectional study was performed to investigate the frequency of CVD in SLE patients in Phramongkutklao Hospital on the basis of medical record documentation. CVD was defined as coronary heart disease, congestive heart failure, cerebrovascular disease (stroke), transient ischemic attack, and peripheral arterial disease (PAD). The associated risk factors of CVD were examined by univariate and multivariate logistic regression analyses. RESULTS: One hundred fifty nine SLE patients were enrolled in the present study. Nine female and one male SLE patients had CVD (prevalence 6.3%). SLE patients with CVD had higher Systemic Lupus International Collaborating Clinics Damage Index (SDI) score (p-value = 0.025) and received higher average dose of corticosteroid (p-value = 0.034) than SLE patients without CVD. Patients with CVD were more likely to present with malar rash (p-value = 0.054), discoid rash (p-value = 0.047), and more likely to used cyclophosphamide (p-value = 0.045) than patients without CVD. SLE patients with CVD were more likely to have diabetes mellitus (p-value = 0.037), antiphospholipid syndrome (p value = 0.055), and had higher proportion of patients whose waist circumference more than 90 centimeters in male or more than 80 centimeters in female (p-value = 0.06) than SLE patients without CVD. The presence of antiphospholipid antibodies was higher in SLE patients with CVD than SLE patients without CVD (p-value = 0.076). The multivariate regression analysis identified that SDI score (odds ratio (OR) = 1.74 with 95% confidence interval (CI) 1.12-2.69, p-value = 0.013), and waist circumference more than 90 centimeters in male or more than 80 centimeters in female (OR = 6.9 with 95% CI 1.20-38.46, p-value = 0.031) were independently associated risk factors for the occurrence of CVD in SLE patients. The presence of antiphospholipid antibodies also had a trend toward increased risk of CVD in SLE patients (OR = 4.1 with 95% CI 0.96-17.8, p-value = 0.057). CONCLUSION: Lupus damage, waist circumference more than 90 centimeters in male or more than 80 centimeters in female were the independent risk factors for CVD in SLE patients. PMID- 27276741 TI - Monitoring of Effectiveness and Safety of Colistin for Therapy in Resistant Gram Negative Bacterial Infections in Hospitalized Patients at Siriraj Hospital. AB - OBJECTIVE: To monitor the effectiveness and safety of colistin for therapy in resistant Gram-negative bacterial infections at Siriraj Hospital 10 years after colistin was first introduced in Thailand at Siriraj Hospital in 2005. MATERIAL AND METHOD: Study subjects were hospitalized adult patients with documented Gram negative bacterial infections that received parenteral colistin (Colistate) for longer than 48 hours between October 2014 and June 2015. Patient information regarding demographics, characteristics of infections, antibiotic therapy, clinical outcomes, microbiological responses, and nephrotoxicity were identified and retrieved from patient medical records. The data were analyzed using descriptive statistics. RESULTS: One hundred thirty eight patients were included in the study. Many of the patients were elderly males. The most common type of infection was pneumonia and A. baumannii was the most common cause of infection. Nearly all isolates of A. baumannii and P. aeruginosa were resistant to carbapenems. A loading dose of colistin (300 mg) was given in 94.9% of patients. Only 19.6% of patients received colistin alone. Most patients received concomitant antibiotics, especially carbapenems, and piperacillin-tazobactam. Favorable clinical outcome was observed in 71.7% of patients at the end of colistin therapy. Patient mortality at the end of colistin therapy and at 30 days after colistin therapy was completed was 23.2% and 39.9%, respectively. Microbiological eradication of target bacteria at the end of colistin therapy was found in 50.0% of patients. Overall incidence of acute kidney injury was 39.9%, with most cases classified as either risk (20.3%) or injury (13%). Colistin related renal dysfunction was reversible in most cases. CONCLUSION: Colistin remains the principal antibiotic in carbapenem-resistant Gram-negative bacterial infections. Colistin's effectiveness and safety is still rated as moderate for therapy in difficult-to-treat resistant Gram-negative bacterial infections. PMID- 27276742 TI - Moringa Oleifera Leaf Increases Insulin Secretion after Single Dose Administration: A Preliminary Study in Healthy Subjects. AB - BACKGROUND: Herbal medicine has long been used as an alternative medicine for treatment of type 2 diabetes mellitus (T2DM). Recently, Moringa oleifera (MO or ma-rum in Thai) leaf has been widely used in T2DM patients. Several studies in diabetes rat model have shown that MO had effect on glucose metabolism. However study in humans is lacking. OBJECTIVE: Examine effects of MO on plasma glucose and insulin secretion. MATERIAL AND METHOD: Ten healthy volunteers were enrolled in this study (mean age 29 +/- 5 years; BMI 20.6 +/- 1.5 kg/m2; FPG 81 +/- 5 mg/dl). After an overnight fast and every two weeks, subjects received an oral dose of MO at increasing dosages of 0, 1, 2, and 4 g. Plasma glucose (PG) and insulin were collected at baseline and at 0.5, 1, 1.5, 2, 4, and 6 hours after each MO dosage administration. Insulin secretion rate was measured using area under the curve (AUC) of insulin and AUC of insulin/glucose ratio. RESULTS: After doses of 0, 1, 2, and 4 g MO, mean plasma insulin increased (2.3 +/- 0.9, 2.7 +/- 1.0, 3.3 +/- 1.4, and 4.1 +/- 1.7 MUU/ml, respectively) despite there being no differences in mean PG (77 +/- 6, 78 +/- 5, 79 +/- 6, and 79 +/- 5 mg/dl, respectively). AUC of insulin was greater after high-dose MO (4 g) than after baseline or low-dose MO capsule (1 g) (24.0 +/- 3.5 vs. 14.5 +/- 1.8 or 16.1 +/- 2.0, respectively; p = 0.03), while there was no difference in AUC of glucose. Accordingly, insulin secretion rate represented by AUC of insulin/glucose ratio after high-dose MO was significantly increased by 74% (P = 0.041), as compared with that of baseline. CONCLUSION: We concluded that high-dose (4 g) MO leaf powder capsules significantly increased insulin secretion in healthy subjects. These results suggest that MO leaf may be a potential agent in the treatment of type 2 diabetes. Further studies of MO in patients with T2DM are needed. PMID- 27276743 TI - Low Sleeping Time, High TV Viewing Time, and Physical Inactivity in School Are Risk Factors for Obesity in Pre-Adolescent Thai Children. AB - OBJECTIVE: Explore the association between physically active behavior and obesity in 7- to 12-years-old Thai children. MATERIAL AND METHOD: As part of SEANUTS Thailand, information on anthropometry, physical activity, and sociodemographic variables were collected in 7- to 12-years-old urban and rural Thai children. Multi-stage sampling technique was used and 1,345 children (32% urban, and 50.3% boys) participated in the study. Anthropometric measurements included weight, height, and BMI-for-age Z-scores (BAZ) using World Health Organization Growth Reference. Obesity was defined as BAZ > 2SD. Physical activity was assessed using a validated physical activity questionnaire (PAQ). The PAQ provided an activity score, activity time in school, sleeping hours, and TV watching time as categorical variable, low, moderate, and high. Chi-square by likelihood ratio test and logistic regression were used to compare obese and non-obese groups. RESULTS: The overall prevalence of overweight and obesity was 10.2 and 10.8% respectively, whereas 8.2% was classified as thin. Maternal education and religion did not differ between obese and non-obese children. However, obese children's family income was higher. After controlling for family income, maternal education, and religion, obese children were significantly less active during break times in school, slept less, and watched more TV than non-obese. However, there was no difference in the activity score of obese and non-obese children. CONCLUSION: The study showed that physical activity during break time in school, sleep duration, and hours of TV viewing were associated with obesity in pre-adolescent Thai children. It is important to note that activity score was not associated with obesity. One of the most important benefits to be physically active in childhood is the potential to maintain this behavior into adulthood. Therefore, programs that encourage healthy behaviors and address these modifiable risk factors should be incorporated in the school curriculum. PMID- 27276744 TI - Risk Factors for Severe Enteroviral Infections in Children. AB - OBJECTIVE: To study the risk factors associated with severe enterovirus infection among hospitalized pediatric patients with hand, foot, and mouth disease (HFMD) at King Narai Hospital, Lopburi, Thailand. MATERIAL AND METHOD: We reviewed all of the suspected enterovirus infection cases aged less than 15 years admitted to King Narai Hospital between 2011 and 2013. Cases were classified into mild and severe enterovirus infection. Risk factors for severe enterovirus infection were analyzed using univariate and multivariate logistic regressions. RESULTS: During the study period, 156 patients met the case definition for further analysis. Of those 156 patients, 131 (84.0%) were classifed as mild cases, and 25 (16.0%) as severe cases with five (3.2%) deaths. The most common manifestations among the severe cases were seizures, pneumonia, meningoencephalitis, meningitis, and hyperglycemia. Of the 31 identifiable cases, 12 were caused by enterovirus 71 (EV71), 12 by coxsackievirus A16 (CA16), four by both, and three by other enterovirus. The clinical manifestations that were significantly related to severe enterovirus infection in univariate analysis were age of less than one year, highest body temperature greater than 39.0 degrees C, duration of fever greater than three days, absence of skin lesions, diarrhea, dyspnea, and hyperglycemia. The clinical manifestations that were significantly related to severe enterovirus infection by both univariate and multivariate analyses were absence of oral lesions, seizures, and drowsiness/lethargy. CONCLUSION: The major pathogens of severe disease were EV71 and CA16. High-risk factors significantly related to severe enterovirus infection in both univariate and multivariate analyses were absence of oral lesions, seizures, and drowsiness/lethargy. Early recognition of children at risk and prompt treatment is important to mitigate the deterioration of patients with enterovirus infection. PMID- 27276745 TI - Correlation between Serum SCCA and CYFRA 2 1-1, Tissue Ki-67, and Clinicopathological Factors in Patients with Esophageal Squamous Cell Carcinoma. AB - BACKGROUND: Squamous cell carcinoma antigen (SCCA) and CYFRA 21-1 have been reported as useful tumor markers for esophageal squamous cell carcinoma (ESCC), but no information has yet been reported about the relationship between these serum tumor markers and tissue proliferative activity (Ki-67) in ESCC patients. OBJECTIVE: To study the correlation between SCCA, CYFRA 21-1, Ki-67, and clinicopathological factors in ESCC patients. MATERIAL AND METHOD: Pretreatment SCCA and CYFRA 21-1 serum levels were measured, while the expression of Ki-67 was assessed on tumor tissue. The associations between these biomarkers, clinicopathological factors, and overall survival were analyzed. RESULTS: One hundred sixty six patients participated in this study. Elevated SCCA and CYFRA 21 1 were found in 78.9% and 50.0% of the patients, respectively, while 42.8% had both serum markers elevated. The SCCA and CYFRA 21-1 levels were not correlated (p = 0.128) to each other nor to age, sex, T N, M location, grade, or Ki-67. High Ki-67 expression levels were significantly correlated with T4 (p = 0.010), M1 (p = 0.010), and poor grade (p = 0.015) but not to age, sex, N, or location. Levels of SCCA, CYFRA 21-1, and Ki-67, alone or in any combination, were not correlated to survival of patients. CONCLUSION: The authors showed that Ki-67 in tumor tissue is probably a more reliable marker than serum SCCA and CYFRA 21-1 in predicting the clinical course of ESCC. PMID- 27276746 TI - DCE-MRI-Derived Parameters as Predictors of Response to Neo-Adjuvant Chemoradiation Treatment of Rectal Carcinoma. AB - BACKGROUND: Preoperative combined chemoradiation treatment (CRT) is now accepted as the treatment of choice due to its benefits of decreasing the primary tumor volume and enhancing the sphincter preservation surgery. Determining whether a patient is responding to therapy is crucial for rectal cancer patients who may benefit from prompt treatment modifications. OBJECTIVE: To evaluate the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the treatment response. MATERIAL AND METHOD: Nineteen patients with histologically proven rectal adenocarcinoma who were candidates for neo-adjuvant CRT were prospectively included. All patients were examined by conventional and DCE-MRi at three time points (pre-, during-, and post-CRT). Surgical resection was performed after complete CRT. The pathological response and Dworak regression grade were assessed. All parameters were blindly analyzed. RESULTS: The median pathologic response rate for all patients was 40%. Dworak regression grades of 0, 1, 2, 3, and 4 were found in 0.0%, 21.1%, 42.1%, 26.3%, and 10.5% of patients, respectively. The tumor thickness and length were 30% and 32.9% lower at during CRT and 40.6% and 44.7% lower post-CRT and had moderate and fair negative correlations with the pathologic response rate and Dworak regression rate, respectively. Among the DCE-MRI parameters, only a change in the time to peak between pre- and during-CRT was correlated with the Dworak regression grade (p = 0.01). The percentage change in the time to peak in patients with poor regression (grades 0-1) was significantly greater than in patients with intermediate/complete regression (grades 2-4) [139.25% vs. 6.13%]. CONCLUSION: Changes in the tumor thickness and length evaluated by conventional MRI and the time to peak evaluated by DCE-MRI during CRT may be useful for predicting the treatment response of rectal cancer patients. PMID- 27276747 TI - Mediastinal Lymphadenopathy in Patients with Systemic Sclerosis. AB - BACKGROUND: There are few studies regarding the characteristics of mediastinal lymphadenopathy (MN) in patients with systemic sclerosis (SSc). Understanding its features could help radiologists interpret lung imaging more confidently. OBJECTIVE: To determine the prevalence and characteristics of MLN in patients with SSc and factors associated with MLN. MATERIAL AND METHOD: A retrospective review of medical records and high resolution computed tomography (HRCT) of the lungs of all patients with SSc at Srinagarind Hospital, Khon Kaen University, Thailand between 2009 and 2011 was done. Univariate and multivariate logistic regressions were used to analyze the outcomes. RESULTS: Sixty patients were eligible for the present study; the majority of them was women (71.7%) and had diffuse SSc (71.7%). The prevalence of MLN was 56.7% (36 in 60 cases). The distribution of MLN was mainly found in two or more locations (47.1%) and had isodensity on imaging (61.3%). The median size of nodes was 1.2 cm (inter quartile range 1, 1.4 cm). Only the pulmonary fibrosis score was significantly associated with MLN with the adjusted odds ratio of 1.2 (95% confidence interval 1.1, 1.4, p = 0.03). There was no association between MLN with other factors. CONCLUSION: MLN was prevalent in patients with SSc. The pulmonary fibrosis score was an independent factor associated with MLN. PMID- 27276748 TI - Non-insulinoma Pancreatogeneous Hypoglycemia Syndrome with False-Positive Somatostatin Receptor Scintigraphy: A Case Report and Review of Literature. AB - Non-insulinoma pancreatogeneous hypoglycemia syndrome (NIPHS) is a rare cause of hypoglycemia in adults. The cause of NIPHS is diffuse hyperinsulinism. As a result, computed tomography (CT) of pancreas, endoscopic pancreatic ultrasonography (EUS), and somatostatin receptor scintigraphy (SSRS), which are usually performed to locate an insulinoma, are not able to diagnose NIPHS. Moreover, SSRS can give a false-positive result. In this case report, we introduce a 22-year-old Thai woman who presented with fasting and postprandial hyperinsulinemic hypoglycemia. Accordingly, an insulinoma was suspected. She underwent several studies to locate the lesion. Pancreatic CT and EUS failed to locate a lesion; however, SSRS showed a faint focus of increased uptake at the pancreatic head. The suspected insulinoma was not identified during a first operation. Thereafter other diagnostic methods were performed in an effort to locate the suspected insulinoma, including selective arterial calcium stimulation test. The result of the selective arterial calcium stimulation test was negative. Intraoperative ultrasonography during a second operation also failed to locate a tumor. Finally, a pancreatic head resection was performed according to SSRS result, yet capillary blood glucose levels did not increase after resection. In response, a 95% pancreatectomy was performed. The pathology report was consistent with diffuse hyperinsulinism. This report emphasizes that SSRS can give false positive result in NIPHS. PMID- 27276749 TI - Impact of Computer Related Posture on the Occurrence of Musculoskeletal Discomfort among Secondary School Students in Lagos, Nigeria. AB - BACKGROUND: Computers have become an essential part of life particularly in industrially advanced countries of the world. Children now have greater accessibility to computers both at school and at home. Recent studies suggest that with this increased exposure, there are associated musculoskeletal disorders (MSDs) in both school-aged children and adults. OBJECTIVES: To assess the posture assumed by secondary school students during computer use and its impact on the occurrence and severity of reported musculoskeletal discomforts. METHODS: Posture assumed during normal computer class, occurrence of discomforts, body parts involved and the intensity of discomforts were evaluated in 235 school aged children using Rapid Upper Limb Assessment (RULA) scale, Body Discomfort Chart (BDC) and Visual Analogue Scale (VAS) before and after normal computer class. Inferential statistics of t-test and chi-square were used to determine significance difference between variables, with level of significant set at p < 0.05. RESULTS: None of the participants demonstrated acceptable posture. Computer use produced significant discomforts on the neck, shoulder and low back. There was a significant relationship between participants height and posture assumed. Two hundred and eleven (89.8%) participants reported discomforts/pain during the use of computer. Weight and height were contributory factors to the occurrence of musculoskeletal discomfort/pain (p < 0.05) in some of the body parts studied. CONCLUSION: Musculoskeletal discomfort was found to be a problem among the school aged children during computer use. Weight and height were implicated as factors that influenced the form of posture and the nature of the reported discomfort. Creating awareness about the knowledge of ergonomics and safety for promotion of good posture was therefore recommended. PMID- 27276750 TI - QT Dispersion in Healthy Adult Nigerians. AB - BACKGROUND: Increase in QT dispersion (QTd) is associated with an increased risk of cardiovascular morbidity and mortality. OBJECTIVES: This study sought to (i) determine the mean QTd and (ii) characterise QTd in a healthy Nigerian population. METHODS: One hundred healthy Nigerian adults were studied. Healthy status of the subjects was determined by history and physical examination. A resting 12- lead ECG was obtained from all subjects for determination of QTc, QTd and ECG left ventricular hypertrophy (LVH) using Sokolow Lyon (SL) and Araoye's codes. Echocardiography was used to determine LV systolic function, LVM and LVMI for 60 subjects. RESULTS: The QTd ranged from 15-70ms with a mean value of 38.5 +/- 11.2ms. QTd was independent of age (p = 0.86), sex (p = 0.97), heart rate (p = 0.22), blood pressure (p > 0.05), BMI (p = 0.81), QTc (p = 0.41), LVH (ECG and echo) and LV systolic function (p > 0.05). CONCLUSION: QT dispersion is independent of demographic parameters, LV systolic function and LV hypertrophy in healthy adult Nigerians. PMID- 27276751 TI - Accidental Peno-Scrotal Degloving Injuries in a Child. A Case Report and Literature Review. AB - Injury to male external genitalia is very rare because of some intrinsic factors like location, strong investing tunica albuginea and cremasteric muscles. However, when it occurs it is considered a urological emergency. Child labour with poor understanding of risks and safety precautions, especially under harsh supervision, surely poses major challenges. This case illustrates degloving injury of the penis and avulsion of the scrotum in a young boy while operating a roller type machine used in palm trees plantation. The penis was primarily regloved and avulsed skin primarily repaired. A good cosmetic outcome was observed from this treatment. This case also illustrates the importance of early presentation and emergency intervention in this condition. PMID- 27276752 TI - Prevalence of Oro-Facial Lesions in Human Immunodeficiency Virus Infected Women in a Nigerian Teaching Hospital. AB - BACKGROUND: Orofacial lesions are among the earliest clinical manifestations of HIV infections. OBJECTIVE: This study to investigate the oral lesions seen in HIV positive women with emphasis on the need for diagnosis of oral lesions by all health workers. METHOD: A prospective cross-sectional study of HIV positive women attending the HIV/AIDS clinic (PEPFAR) of the University of Benin Teaching Hospital, Benin-city, Nigeria. The subjects were investigated for the presence of oral lesions, between the period January and March, 2011. The study was approved by the ethics committee of the hospital and a written informed consent was obtained from each subject that participated in the study. Determination of HIV related oral lesions was carried out clinically using the criteria proposed by the ECC/WHO, 1993. P values <= 0.05 were considered significant. RESULTS: A total of 107 HIV/AIDS infected women attending the HIV/AIDS Clinic were examined. The age ranged from 18 to 50 years with mean age of 36 +/- 9.2 years. The age group of 21 to 30 was the most affected (n = 36, 33.6%). Sixty-one subjects (57.0%) presented with oral lesions. The most common observed oral lesion was pseudomembranous candidiasis (n = 37, 37.8%); followed by melanotic pigmentation (n = 11, 11.2%) and xerostomia (n = 11, 11.2%). Group 1 oral lesions accounted for 64.3%, group 2 accounted for 30.6%, while group 3 accounted for 5.1%. CONCLUSION: Oro-facial lesions are among the earliest clinical manifestations of HIV infection. These were commonly observed in HIV infected Nigerian women. Oral candidiasis the most common oral lesion observed in the series may therefore be used as a clinical indicator of early immunodeficiency associated with HIV. PMID- 27276753 TI - Improving First Aid Management of Epilepsy by Trainee Teachers of the Federal College of Education (Technical), Akoka - Lagos, South West Nigeria--Can Health Education have an Effect? AB - BACKGROUND: lt is estimated that epilepsy affects approximately 50 million people worldwide and about 40 million of them live in developing countries. Studies have indicated high rates of poor knowledge, negative attitude and poor first aid management skills of students with epilepsy among practicing teachers. However, there is paucity of such studies on trainee teachers to ascertain any similarities or differences (if any) and the effect of educational interventions. OBJECTIVE: To determine the effect of a health education intervention on trainee teachers' knowledge, attitude and first aid management of epilepsy. METHODS: The effect of a health education intervention in first aid management of epilepsy was assessed among 226 trainee teachers, attending the Federal College of Education (Technical), Akoka. This was done using a quasi-experimental study design. Data were analyzed using the SPSS version 15. RESULTS: The respondents had a median age of 22 years with a range of 18 to 56 years. The majority of them were females (68.6%), single (79.2%), Christians (81.9%), Yoruba (70.4%) and in first year (100 level) of their study (69.9%). The highest proportion was from the Accounting department (46.0%). A consistent increase in responses to items on knowledge, attitude and first aid management of epileptic seizure items from baseline to post-intervention was observed. For instance, the proportion of responses that epileptic seizures originate from the brain significantly (p = 0.025) increased from 62.5% at baseline to 74.1% after intervention. Generally, slightly more than two-fifths (44.2%) and about two thirds (61.9%) of the respondents were observed to have poor knowledge and negative attitude to epilepsy respectively at baseline. Overall, giving health education on epilepsy led to a reduction in the proportion of respondents with poor knowledge by 15.5% (increase of good knowledge by 29.6%), decrease of negative attitude by 16.4% and increase of good first aid management skill by 25.0%. The knowledge scores were significantly associated with age (p = 0.001), marital status (p = 0.003) and department (p = 0.004) while the attitude scores were significantly associated with teaching duration (p = 0.020). The knowledge was predicted by department (p = 0.001) while the attitude was predicted by teaching duration (p = 0.036). CONCLUSION: This study reveals that health education could improve the knowledge, attitude. and first aid management of students with epilepsy among trainee teachers. It is therefore proposed that an intervention programme on baseline knowledge of epilepsy and its first aid management be incorporated into the teacher-training curriculum, particularly those in health-related programmes, to address their deficiencies in knowledge, attitude and first aid management of students with epilepsy. PMID- 27276754 TI - Chronic Ulcers in Ikeja-Lagos, Nigeria: an eighteen month review of infecting bacterial agents and susceptibility pattern. AB - BACKGROUND: Chronic ulcers are an important cause of morbidity among surgical and medical patients. Infection in ulcers may delay healing and cause septicemia resulting in mortality. Microbial studies are important for the appropriate management of these ulcers. METHODS: Details of all patients treated for ulcers that were investigated at the department of Medical Microbiology and Parasitology, Lagos State University Teaching Hospital, Ikeja-Lagos, Nigeria between July 1st 2009 and December 31, 2010 were retrieved from the computer database and transferred into the proforma designed for the study. Data collected were demography, date of onset of ulcer, mode of specimen collection, names of isolates and drug sensitivity patterns. RESULTS: A total of 329 cases were seen and reviewed during the study period. Males constituted 50.2%, females 38.3% and the gender of the remaining 11.6% were not indicated. There were 259 (78.7%) adults and 42 (12.8%) children. The ages of 28 cases were not indicated. Microbial growths were obtained in 217 (66.7%) patients. Gram negative (Gn) organisms were isolated in 181 (83.5%) and Gram positive (Gp) in 35 (16%). The most common isolates were Pseudomonas aeruginosa (19.1%) Staphylococcus aureus (9.7%), Proteus mirabilis (7.6%) and Escherichia coli (7.3%). There were widespread resistances by the isolates to the common antibiotics in the study environment. CONCLUSIONS: The wide spread resistance may be due to lack of an antibiotic use policy. Certain antibiotics should be reserved for second line treatment in the emergency setting. PMID- 27276755 TI - Quality of Referral Letters to the Paediatric Department of a Tertiary Hospital in Nigeria. AB - BACKGROUND: The referral letter is a flexible means of transmitting information about the care of patients from one healthcare worker to another. In developing regions of the world like Africa, where it may serve as the only means of transferring patient's information, the referral letter has infrequently been studied. OBJECTIVE: The study is to assess the quality of referral letters to the Paediatric department of a tertiary hospital in Nigeria. METHODS: Referral letters sent to the Olikoye Ransome-Kuti Emergency Center (ORKCEC) and the Paediatric Outpatient Clinics of the Lagos University Teaching (LUTH) between December 2012 and February 2013 were reviewed for content of information. Letter sent to the emergency center were compared with letter sent from sources within LUTH. RESULTS: A total of 356 letters were reviewed, with 196 (55.1%) letters sent to the Emergency center. The majority of the referral letters (262; 73.6%) were from hospitals other than LUTH-(inter-hospital). Patient's name (99.7%), name of referring hospital (93.3%) and presenting complaints (91.1%) were the most consistently filled. Information relating to adverse clinical warning (1.7%), request for feedback (4.2%) and urgency of referral (8.4%), were the least filled. Only in 28.4% of the letters were the results of any or all the investigations done included. More interhospital letters had information on findings on physical examination, treatment, urgency of referral and request for feed-back from the receiving specialists. Referral letters to the clinics were more likely than letters to emergency centre to contain information on presenting complaints, history of the presenting complaints, and findings on physical examination. CONCLUSION: Referral letters sent to the paediatric department of LUTH are poorly written with significant information about patient care frequently missing. Interhospital referral letters and letters sent to the clinics, though similarly low in quality, were more likely to contain information on physical findings and treatment received. PMID- 27276756 TI - Anaemia Prevention In Pregnancy Among Antenatal Clinic Attendees In A General Hospital In Lagos. AB - BACKGROUND: Anemia is the world's second leading cause of disability and thus one of the most serious global public health problems. The World Health Organization (WHO) estimates that an average of 56% of pregnant women in developing countries, are anaemic. OBJECTIVES: This study was conducted to. determine the knowledge, attitude and practices of prevention of anaemia in pregnancy amongst pregnant women attending the Antenatal Clinic at Ifako-Ijaiye General Hospital. METHODS: The design was cross-sectional descriptive study. Simple random sampling method was used to select two hundred and twenty respondents (220). A pretested, structured, interviewer administered questionnaires were used for data collection. RESULTS: Majority (95%) of the respondents was aware of anemia in pregnancy but the mean knowledge score was 56.5%. Less than half (46.3%) of the respondents thought that contraceptives could help prevent anemia in pregnancy by reducing closely spaced pregnancies. Only 31.8% were compliant with the use of iron supplements. About one third (33.2%) didn't combine drinking tea with meals while 47.3% of the respondents didn't use iron supplements with milk products. CONCLUSION: The study showed that most of the respondents had a moderate level of knowledge, and positive attitude towards contraceptive use but a high proportion were not compliant with the daily use of iron supplements. It is recommended that health education of women as well as close family members should be reinforced to improve the compliance with supplements. PMID- 27276757 TI - Parental determinants of offspring head circumference using a sample of patients attending a government hospital in Lagos, Nigeria. AB - BACKGROUND: Head circumference at birth is an important neonatal parameter in view of its association with perinatal and postnatal morbidity and mortality. It is an indicator of brain volume and a tool for assessing the development of the central nervous system. Being a complex hereditary trait, predicting baby's head circumference from parental anthropometrics could complement the already existing ultrasonographic method of prediction. OBJECTIVE: To identify the parental anthropometric determinants of baby's head circumference in Lagos, Nigeria, using a sample of patients attending a government hospital. METHODS: Parental anthropometric parameters were obtained from 250 couples. The baby's head circumference was measured immediately after birth. The data were subjected to multivariate analysis. RESULTS: The parental variables that were most predictive of babies' head circumference were mid-parental weight, maternal height, maternal weight gain during pregnancy and maternal age. CONCLUSION: Assessment of these parental attributes can complement ultrasonographic data in predicting baby's head circumference for better perinatal outcome. PMID- 27276758 TI - Therapeutic Effects of Exercise Training On Selected Cardio-Pulmonary Parameters and Body Composition of Nigerians with Chronic Heart Failure (A Preliminary Study). AB - BACKGROUND: The use of exercise training in the management of individuals with chronic heart failure has not been widely accepted by health care providers especially in Sub-Saharan Africa because of the possibility that the failing hearts may have a negative response to the increased workload and stress of exercise. OBJECTIVE: The study aimed to evaluate the effects of exercise training (ET) on selected cardio-respiratory and body composition variables of Nigerians with chronic heart failure (CHF). METHODS: Thirty two Nigerians with CHF (male - 17), aged 30 to 71 years, mean age 54.2 +/- 1.9 years and New York Heart Association Functional Class (NYHA) II-III recruited from Cardiology Clinic of Lagos University Teaching Hospital Nigeria participated in the study. They were randomized into exercise (EG) and control groups (CG). Exercise group performed 12-weeks of aerobic and resistance training for 60 minutes, three sessions per week. Selected cardio-respiratory and body composition variables were measured pre and post intervention in both groups. Data was analyzed using SPSS-17 package. Level of significance was set at 0.05. RESULTS: There was no significant difference in the measured variables between the groups at baseline (p > 0.05). Significant improvement was seen in EG in all the measured variables except the systolic (p = 0.29) and diastolic blood pressure (p = 0.45). No adverse effect was observed during the exercise training. No significant improvement was observed in the control group (p > 0.05). CONCLUSION: Exercise training may improve cardiorespiratory and body composition variables in patients with chronic heart failure. PMID- 27276759 TI - Undergraduate Students' Knowledge and Practice of Gonorrhea and other Sexually Transmitted Infections. AB - BACKGROUND: Sexually transmitted infections (STIs) are a major public health issue. Adolescents and youth (15-24 years) are the age groups at the greater risk for acquiring them. Also a large percentage of new STIs occur in this age group with 7000 young people worldwide acquiring the infection every day. Sexually transmitted infections (STIs) are poorly recognized and inadequately treated in Nigeria despite the fact that they constitute a major risk factor for sexual transmission of HIV infection. The shortage of trained human resources is among the most important obstacles to strengthening health systems in low-income countries. OBJECTIVE: This study is to document the knowledge and practice of undergraduate students about gonorrhoea and other STIs as a baseline survey for future intervention work. METHODS: It was a questionnaire-based, cross sectional descriptive study of the knowledge and practice of STIs among students in the seven public tertiary academic institutions in Lagos State using list obtained from the Lagos State Ministry of Education. Thirty (30) students who agreed to be surveyed were conveniently selected from each school. Pre-tested, semi structured, validated questionnaires were administered and collected back. Data was entered into Microsoft Excel and analysed using EPI Info, SPSS version 15 and Microsoft Excel. Results were considered to be statistically significant if p < 0.05. RESULTS: Majority of the respondents were of the 21 - 25 year age range (48%) and were mainly single (95%), Christian (61%) and Yoruba (81%). About 51% of the respondents had at least good knowledge of gonorrhoea and other STIs. Knowledge about symptoms and transmission was higher than knowledge of prevention, consequences and drugs. Among those that are sexually active 24% do not use condom while 10% reuse condom. Use of both modern and traditional medical practitioners (TMP) was documented among the students. CONCLUSIONS: Awareness programs with key messages about gonorrhoea and other STIs should be developed and circulated widely in tertiary institutions in the state to improve students' practice. Also strategies to embrace TMP for STI management should be evolved. PMID- 27276760 TI - Pathway to Independence: Implications for Developing A Sustainable MIS Program in low Resource settings. AB - BACKGROUND: Gastrointestinal surgery has been at the forefront of advances in minimally invasive surgery (MIS). In the low resource settings of the developing countries, despite the benefits of MIS, its uptake in sub-Saharan African countries has been slow. OBJECTIVE: The present study reports the process of developing a minimally-invasive surgery service line as well as surgical outcomes in LASUTH. METHODS. We reviewed medical records of all patients who underwent minimally invasive surgery at LASUTH between March 2011 and March 2012. During each of three training missions in LASUTH patients with Gastrointestinal and gynaecological surgical conditions were carefully selected, and prepared for surgery. All patients were admitted a day prior to surgery. A description of the surgical technique and the skills training used is also presented. RESULTS: A total of 24 laparoscopic procedures were performed between March 2011 and March 2012. There were more females 17(70.8%) than males 7(29.2%), with a female to male ratio of 2.5:1. The age range was from 18 yrs to 75 yrs with a peak in the age group between 21-30 yrs. The chief complaints were right hypochondrial pain in 9 cases (37.5%) and right iliac fossa pain in 6 cases (25%) whilst others were right groin swelling, dysphagia, infertility and intersex state. CONCLUSION: The results presented in respect of conversion rate, length of post operative stay and complications rate are similar to the pattern in more established centers. The use of team training as done in LASUTH helps to accelerate the rate of learning and ensures sustainability. PMID- 27276761 TI - Practical Approach to the Management of the Severely Injured. AB - Events associated with severely injured victims are common occurrences. These injured patients should be properly managed to achieve good outcome. Trauma algorithm protocols are known to improve therapeutic process and outcome. However, most hospitals in our subregion that attend to severely injured patients are yet to develop an algorithm treatment protocols for the management of these patients. The ambulance system in Nigeria is still un-coordinated and unsupervised. Most of the existing ambulances are not well equipped and usually not manned by experienced paramedics. Therefore, transfer of severely injured victims is fraught with danger during transit. Communication link to inform the trauma centres ahead of transfer is virtually non-existent. Upgrading of the trauma systems in Nigeria is necessary to prevent unnecessary mortality among the resourceful age group that are mostly affected by events causing severely injured patients . PMID- 27276762 TI - Cytokines, Type 2 DM and the Metabolic Syndrome. AB - BACKGROUND: Inflammatory markers have been widely implicated in Diabetes Mellitus (DM) and the metabolic syndrome (Mets). Data on the association of cytokines (pro inflammatory mediators) and components of the Mets are sparse in sub Saharan Africa. OBJECTIVE: We sought to document the pattern of distribution of cytokines in Nigerian subjects with type 2 DM and compare cytokine levels between DM subjects with and without the Mets. METHODS: 200 subjects with type 2 DM and 100 healthy sex and aged matched Controls were studied. Anthropometric indices, lipid parameters and cytokine levels, which included interleukin 10 (IL-10), tumour necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma) and C reactive protein (CRP) were determined. Continuous variables were compared between subjects with type 2 DM and the controls and also between DM subjects with and without the Mets. RESULTS: The mean levels of all studied cytokines were significantly higher in the subjects with type 2 DM than the Control subjects, save for IFN-gamma which was significantly lower in type 2 DM. The mean cytokine levels were comparable in the DM subjects with and without the Mets and also comparable in obese DM and non obese DM subjects. Of the Mets defining criteria, waist circumference (WC) and Triglyceride (TG) were found to be significantly associated with only two of the studied cytokines. The correlation coefficient and p values of these findings are as follows: WC vs TNF-alpha (r = 0.16, p = 0.001) and TG vs CRP (r = 0.15, p = 0.03). Multiple regression analyses showed that the cytokines were linearly associated with each other but not with other clinical and biochemical variables. The cytokines were found to be interrelated. IL-10 with a beta value of 0.14 predicted the presence of INF-gamma with a 95% confidence interval of 0.000 - 0.109 and a p value of 0.05. TNF-alpha with a beta value of 0.17 predicted the presence of IL-10 with a 95% confidence interval of 0.004 - 0.034 and a p value of 0.01. IL-10 with a beta value of 0.17 predicted the presence of TNF-alpha with a 95% confidence interval of 0.3-0.590 and a p value of 0.01. CONCLUSION: Cytokine levels are higher in DM than non DM subjects; however, the cytokine levels are not strongly associated with the Mets. Limited correlations were found between each of the cytokines and the parameters of the Mets. Further studies on this entity amongst Africans should be carried out to ascertain if these results are peculiar to DM subjects in sub- Saharan Africa. PMID- 27276763 TI - Antidiarrhoeal Activity of Hydroethanolic Leaf Extract of Bryophyllum pinnatum Lam. Kurtz (Crassulaceae). AB - BACKGROUND: Bryophyllum pinnatum Lam. Kurtz (Crassulaceae) is used in traditional African medicine in the treatment of diarrhoea. OBJECTIVE: To investigate the antidiarrhoeal action of the hydroethanolic leaf extract of Bryophyllum pinnatum (BP). METHODS: Normal intestinal transit, castor oil-induced intestinal transit, castor oil-induced diarrhoea, gastric emptying and enteropooling models in rodents were used to investigate antidiarrhoeal effect. The possible mechanism of antidiarrhoeal activity was investigated using prazosin (1 mg/kg, s.c; alpha1, adrenoceptor antagonist), yohimbine (1 mg/kg, s.c; alpha2 adrenoceptor antagonist), propranolol (1 mg/kg, i.p; alpha- adrenoceptor non-selective antagonist), atropine (1 mg/kg, s.c; muscarinic cholinergic antagonist), pilocarpine (1 mg/kg, s.c; muscarinic cholinergic agonist), and isosorbide dinitrate (IDN) (150 mg/kg, p.o; nitric oxide donor). RESULTS: BP (25-100 mg/kg, p.o) produced dose-dependent and significant (P < 0.001) decrease in intestinal propulsion in normal and castor oil-induced intestinal transit models in comparison to distilled water (10 ml/kg, p.o.) treated control. This antidiarrhoeal effect was inhibited by propranolol pretreatment but yohimbine, prazosin, or atropine pretreatment failed to block this effect. BP treatment reduced the increased peristaltic activity induced by pilocarpine, however, co treatment with IDN significantly (P < 0.001) enhanced the antidiarrhoeal effect of the extract. In castor oil-induced diarrhoea test, the extract produced a dose dependent and significant (P < 0.001) increase in onset of diarrhoea, decreased diarrhoea score, the number and weight of wet stools when compared to control. The in vivo antidiarrhoeal index (ADI(in) vivo)) of 53.52 produced by the extract (50 mg/kg, p.o.) was similar to 76.28 ADI(in vivo) produced by morphine (10 mg/kg, s.c.). The extract produced dose- dependent and significant (P < 0.05; P < 0.001) decrease in the weight and volume of intestinal content in the intestinal fluid accumulation model. In gastric emptying test, BP treatment reduced the quantity of test meal emptied in 1 h but not significant. CONCLUSION: The results showed that the hydroethanolic leaf extract of Bryophyllum pinnatum possesses antidiarrhoeal activity possibly mediated by interaction with beta adrenoceptor, muscarinic cholinergic receptor and nitric oxide pathway. PMID- 27276764 TI - Condom use among antiretroviral therapy naive people living with HIV at a tertiary health care hospital in Lagos, Nigeria: implication for prevention of new infections. AB - BACKGROUND: The consistent use of male latex condom significantly reduces the risk of HIV infection among men and women. OBJECTIVE: This study was designed to assess the prevalence and pattern of male and female condom use among antiretroviral therapy naive people living with HIV (PLHIV) in Lagos, Nigeria. METHODS: This was a cross-sectional descriptive study. Interviewer administered questionnaires were used to collect demographic data of age, gender, marital status, rate, pattern of and reasons for not using condoms among PLHIV. RESULTS: Four hundred and forty three respondents were interviewed with age rangefrom 14 to 75 years and a mean of 35 +/- 9 years. There were 175 (39.5%) males and 268 (60.5%) females in the study. Overall, 71 (16.0%) of respondents used condom consistently. Only 55 (12.4%) of the respondents were aware of female condom while 9 (2%) used it. CONCLUSION: This study reveals that there is a low consistent use of male condoms and a very low awareness and use of female condoms among studied PLHIV. PMID- 27276765 TI - Histolopathological Patterns of Cervical Carcinoma Seen at A Radiotherapy Centre in Ibadan, Nigeria. AB - INTRODUCTION: The treatment of cervical carcinoma is dependent on many factors including histological types and degree of differentiation. Degree of differentiation is an important consideration in determining the prognostic outcome. OBJECTIVE: The study is to describe the histological pattern of cervicer cancer seen in our practice with emphasis on tumour differentiation. METHOD: This retrospective study was carried out within Radiotherapy Department of University College Hospital, Ibadan. The records of patients diagnosed of cervical cancer seen between July 2008 and June 2010 were analysed. Data pulled out included age, disease stage at presentation, histological variant and degree of differentiation. RESULTS: 206 patients were seen during the period of which 196 had complete data. Squamous cell carcinoma (SCC) was seen in 178 patients (i.e. 90.8%) while 14 patients (7.1%) had adenocarcinoma. One patient each had adenoid cystic carcinoma, adenosquamous carcinoma, clear cell carcinoma and mucinous carcinoma. Majority of the patients, 99 (50.5%) had poorly differentiated tumours, 64 (32.7%) had well differentiated tumours, while the rest 33 (16.8%) had moderately differentiated tumours. Of the SCC tumours, 95 (53.4%) were poorly differentiated, 58 (32.6%) well differentiated while the remaining 25 (14%) were moderately differentiated. In comparison only 3 of the 14 adenocarcinoma cases (21.4%) were poorly differentiated, 5 cases (35.7%) were well differentiated, while 6 (42.9%) were moderately differentiated. The difference in the degree of differentiation between squamous histology and adenocarcinoma was statistically significant (p value = 0.002). CONCLUSION: Poorly differentiated squamous cell carcinoma remains the leading variants of cervical cancer seen in our environment. PMID- 27276766 TI - Preliminary Anti-Fungal Activity of the Aqueous Bark Extract of Calotropis procera (ASCLEPIADACEAE). AB - BACKGROUND: Calotropis procera is a species of flowering plant which belongs to the Asclepiadaceous family. Its other names are Apple of Sodom, Giant Milkweed and Swallow-wort. It's native to Africa and Asian countries where they exist as a spreading shrub or small tree with height of about 4m. They. exude copious milky sap when cut or broken. It has a broad grey-green leaves with a pointed tip, two rounded basal lobes and no leaf stalk. Their flowers are waxy white. The different part of this plant has been used for different medicinal purposes such as cure of leprosy, eczema, inflammation, cutaneous infections, syphilis, malarial and low hectic fevers, and as abortifacient. OBJECTIVE: The extract of the bark of the plant Calotropis procera used locally by people in Sokoto to treat ringworm infection was investigated for the claimed activity by subjecting the extract collected to both phytochemical and antifungal screening. METHODS: The extracts of water, n-hexane, petroleum ether and chloroform of the bark of the plant Calotropis procera were evaluated for the presence of alkaloids, tannins, glycosides, saponins, steroids and flavonoids. And the water extract which is often used by the local people was tested for antifungal activity using Sabouraud Dextrose Agar (SDA) in Kirby-Bauer disc diffusion method developed by Kirby et al. Fulcin tablet was used as a standard and two petridishes that does not contain the extracts were used as control. RESULTS: In the phytochemical study using extracts of n-hexane, petroleum ether, chloroform and water, the presence of alkaloids, tannins, saponins and steroids (cardiac glycoside) were confirmed. Also, for the antifungal activity of the plant, there was a complete inhibition of Microsporum specie and Trichophyton specie in the sample after 10 days of inoculation when water extract at different concentrations (i.e. 20 mg/L, 30 mg/L and 40 mg/L) were applied. The tablet only completely inhibited Trichophyton specie. Epidermophyton specie was not found in the sample. The inhibitory effect of this extract was significant (p < 0.05) when compared with fulcin tablet. CONCLUSION: The research confirmed that the extract of the bark of the plant Calotropis procera has some antifungal activity. PMID- 27276767 TI - PREDICTORS OF DIFFICULT AIRWAY MANAGEMENT IN THYROID SURGERY: A FIVE-YEAR OBSERVATIONAL SINGLE-CENTER PROSPECTIVE STUDY. AB - Difficult tracheal intubation (DI) is more common in thyroid than in other surgical branches due to thyromegaly. Proper preoperative airway evaluation is necessary in order to reduce the potential numerous complications. The study examined the incidence of DI in thyroid surgery and the influence of tracheal dislocation and other risk factors on DI. A prospective study was conducted on 2379 patients who underwent thyroidectomy at the Center for Endocrine Surgery, Clinical Center of Serbia, from 2007 to 2012. Patients were divided into groups with (n = 162) and without DI (n = 2217). Besides tracheal dislocation, another 13 risk factors contained in 13 screening tests and three additional factors of gender, age and diagnosis were defined. The incidence of DI in our study was 6.81%. The presence of tracheal dislocation was statistically significant, but not an independent predictor of DI. The diagnosis, large circumference and small neck length, previous DI, recessive mandible, tooth characteristics and oral anomalies were the most significant and independent predictors of DI. Neck circumference and small neck length had highest sensitivity. Previous DI had highest specificity. Thyromegaly, if causing tracheal dislocation and/or stenosis, represents a significant DI predictor, not individually, but in combination with other factors. PMID- 27276768 TI - PRACTICAL CHRONIC PAIN ASSESSMENT TOOLS IN CLINICAL PRACTICE. AB - The aim of the study was to show the role of tools in the evaluation of chronic pain (CP) in general practitioner (GP) everyday clinical practice. The study was done by analyzing electronic database of the first visits of 1090 CP patients referred to the Pain Clinic of the Karlovac General Hospital, Karlovac, Croatia, by their GPs. All patient records were analyzed according to the cause of CP, strongest pain a week before the examination, quality of sleep, and the Patients' Global Impression of Change scale. All statistical analyses were done using the IBM SPSS Statistics version 19.0.0.1 (www.spss.com). CP predominantly occurs in older age group. Patients with musculoskeletal pain accounted for the highest percentage (n = 316; 29%), followed by those with neuropathic pain (n = 253; 23.20%) and those with low back pain (n = 225; 20.60%). The mean pain intensity rating scale score was 8.3 +/- 1.8 a week before the examination and the mean quality of sleep score was 6.8 +/- 1.9. Moderate and severe sleep quality disorder was significantly present in patients over 65 years of age (p = 0.007), patients with musculoskeletal and neuropathic pain, back pain, and those having rated Patients' Global Impression of Change scale as worsening (p = 0.001). The severity of pain and poor quality of sleep are the leading causes of deterioration of the Patients' Global Impression of Change scale in patients suffering from musculoskeletal and neuropathic pain. In order to treat CP comprehensively, it is important for GPs to evaluate the outcomes of clinical treatment using tools for CP assessment. PMID- 27276769 TI - EVALUATION AND MANAGEMENT OF DIFFICULT AIRWAY IN OBESITY A SINGLE CENTER RETROSPECTIVE STUDY. AB - The primary aim of this single center retrospective study was to evaluate difficult mask ventilation (DMV) and difficult laryngoscopy (DL) in a unique group of obese patients. A total of 427 adult patients with body mass index (BMI) >= 25 and surgically treated for endometrial cancer from 2011 to 2014 were assessed. Additional increase in BMI, comorbidities, bedside screening tests for risk factors, and the tools used to manage the patients were noted and their effects on DMV and/or DL investigated. Every escalation in the number of risk factors increased the probability of DMV 2.2-fold, DL 1.8-fold and DMV+DL 3.0 fold. Among bedside tests, limited neck movement (LNM), short neck (SN) and absence of teeth were significant for DMV (p < 0.05), LNM, SN and obstructive sleep apnea for DL (p < 0.05), and LNM and SN for DMV+DL (p < 0.05). However, a 10-point increase of BMI was not an independent risk factor when patients with BMI > 25% were considered. In conclusion, LNM and SN are independent risk factors for developing DMV and/or DL in obese endometrial cancer patients, while BMI increase over 30 was not additionally affecting difficult airway. PMID- 27276770 TI - EARLY VERSUS LATE PERCUTANEOUS TRACHEOTOMY IN CRITICALLY ILL PATIENTS: A RETROSPECTIVE SINGLE CENTER OBSERVATIONAL STUDY. AB - Despite decades of experience in tracheotomy, there still exists a controversy over its ideal timing. The aim of our study was to compare the impact of early and late percutaneous tracheotomy in terms of their ability to reduce mechanical ventilation duration and length of stay in Intensive Care Unit, as well as the frequency of ventilator-associated pneumonia and mortality rates in tracheotomized patients. This retrospective observational study indicated that early tracheotomy in surgical and neurosurgical patients was associated with a reduced duration of mechanical ventilation and reduced length of stay in Intensive Care Unit, but was unable to reduce the frequency of ventilator associated pneumonia and mortality. The reason behind the shorter duration of mechanical ventilation and shorter length of stay in Intensive Care Unit in the early tracheotomy arm was shorter duration of mechanical ventilation carried out prior to tracheotomy, while the duration of mechanical ventilation and the length of stay in Intensive Care Unit after tracheotomy were similar in both groups, suggesting that the procedure itself and not its timing influenced the duration of mechanical ventilation and the length of stay in Intensive Care Unit of tracheotomized patients. PMID- 27276772 TI - FIBEROPTIC BRONCHOSCOPY VERSUS VIDEO LARYNGOSCOPY IN PEDIATRIC AIRWAY MANAGEMENT. AB - The primary goal of pediatric airway management is to ensure oxygenation and ventilation. Routine airway management in healthy pediatric patients is normally easy in experienced hands. Really difficult pediatric airway is rare and usually is associated with anatomically and physiologically important findings such as congenital abnormalities and syndromes, trauma, infection, swelling and burns. Using predictors of difficult intubation should be mandatory preoperative assessment in pediatric patients. Difficult airway algorithm for pediatric patients has to consist of three parts: oxygenation (A), tracheal intubation (B), and rescue (C). According to this new algorithm, if conventional direct laryngoscopy fails, we have to use alternative glottic visualization device. Do we really need video laryngoscopy? If we look at numbers, we might estimate that conventional laryngoscopy is successful and effective in around 98.5% of cases. Do we need to replace Macintosh laryngoscope with video laryngoscope completely in our routine practice? Should video laryngoscope be available to replace fiberoptic intubation in pediatric airway management? According to the algorithm, fiberoptic-assisted tracheal intubation combined with extraglottic airway devices is the standard of care. Establishment of protocols for equipping and maintaining airway trolleys and regular training in their use must be provided to avoid tissue hypoxia in children with compromised airway. PMID- 27276771 TI - CHALLENGES IN THE USE OF VIDEO LARYNGOSCOPES. AB - Despite the lack of uniformity and the need of further investigation, video laryngoscopy continues to gain popularity both inside and outside the operating room. It has quickly become a first line strategy for potential and/or encountered difficult intubation. It is well established that video laryngoscope improves laryngeal view as compared with direct laryngoscopy in patients with suspected difficult intubation and simulated difficult airway scenarios. For novices and experienced anesthesiologists alike, video laryngoscopy is easy to use and the skills involved are easy to master. However, it is important to say that video laryngoscopes may be used in a variety of clinical scenarios and settings because of the video laryngoscope design offering an alternative intubation technique in both anaesthetized and awake patients. The aim of this article is to show and highlight clinical situations in which the use of video laryngoscope is a challenge for an experienced anesthesiologist in solving the airway. Challenges in the use of video laryngoscope with which we deal and encounter in everyday clinical practice that are discussed in this paper are intubation in the prehospital setting and emergency departments, intubation in Intensive Care Unit, intubation in a patient with cervical spine immobilization, and awake video laryngoscopy-assisted tracheal intubation in the obese. We also point out the important role of video laryngoscope as a tool for teaching and training in airway education. Training and education in difficult airway management is essential to improve patient safety at endotracheal intubation in emergency situation. PMID- 27276773 TI - SIMPLE, TIMELY, SAFELY? LARYNGEAL MASK AND PEDIATRIC AIRWAY. AB - Laryngeal mask airway (LMA) was a useful, powerful airway management device for routine pediatric airway management, pediatric difficult airway, and in pediatric emergency situations. Over years, various designs, induction and insertion techniques have been described. LMA provides ease of placement and removal as compared with endotracheal intubation, less traumatism for the respiratory tract, better tolerability by patients, improved hemodynamic stability during emergency, less coughing, less sore throat, avoidance of laryngoscopy, and hands free airway. On the other hand, LMA is not suitable to overcome functional airway problems and mechanical airway obstruction in children. Simple airway management in pediatric patients is normally easy in experienced hands, for anesthesiologists working in specialized hospitals with appropriate personnel and equipment that guarantee optimal safety in these patients. On the other hand, pediatric airway management is a great challenge for anesthesiologists working in departments with a small number of pediatric surgical procedures. Careful preoperative evaluation, preparation and training in the recognition of challenges in pediatric airway are essential for the management of the airway in children. LMA plays a special role in the management of difficult pediatric airway; as a supraglottic airway device, it is incorporated into difficult pediatric airway algorithms. PMID- 27276774 TI - AIRWAY VISUALIZATION: EYES SEE WHAT MIND KNOWS. AB - Airway management is basic for anesthesia practice, and sometimes it can represent a really dramatic scenario for both the patient and the physicians. Laryngoscopy has been the gold standard of airway visualization for more than 60 years, showing its limitations and failure rates with time. New technology has made available an opportunity to move the physician's eye inside patient airways thanks to video laryngoscopy and video assisted airway management technique. Undoubtedly, we have entered a new era of high resolution airway visualization and different approach in airway instrumentation. Nevertheless, each new technology needs time to be tested and considered reliable, and pitfalls and limitations may come out with careful and long lasting analysis, so it is probably not the right time yet to promote video assisted approach as a new gold standard for airway visualization, despite the fact that it certainly offers some new prospects. In any case, whatever the visualization approach, no patient dies because of missed airway visualization or failed intubation, but due to failed ventilation, which remains without doubt the gold standard of any patient safety goal and airway management technique. PMID- 27276775 TI - CHALLENGES OF OBSTETRIC ANESTHESIA: DIFFICULT LARYNGEAL VISUALIZATION. AB - Obstetric anesthesia is one of the high risk subspecialties of anesthesia practice. Anesthesia related complications are the sixth leading cause of maternal mortality. Difficult or failed intubation following induction of general anesthesia for CS remains the major contributory factor to anesthesia-related maternal complications. The airway management of obstetric patients is a challenging issue for several reasons. Anatomic and physiologic changes related to pregnancy may increase the difficult and failed intubation rates compared to the general surgical population. Proper evaluation of the airway anatomy and airway structures is vital to prevent airway management related catastrophes. In addition to basic airway and intubation equipment, each anesthesia department must have difficult intubation equipment cart including fiber optic laryngoscope, video laryngoscopes, and different types of laryngeal masks. It is essential that all anesthesiologists have a preconceived and well thought-out algorithm and emergency airway equipment to deal with airway emergencies during difficult or failed intubation of a parturient. PMID- 27276776 TI - VISUALIZATION OF AIRWAY. AB - The author provides an overview of the history of optical instruments for airway management in anesthesiology. It systematically demonstrates the development of laryngoscope down to the present time when video laryngoscope has been introduced in clinical practice. PMID- 27276777 TI - ALTERNATIVE DEVICES IN AIRWAY VISUALIZATION. AB - The Macintosh laryngoscope has been the most widely used device for intubation since its invention by Foregger in the 1940s. Recently, video and optic laryngoscopy assisted tracheal intubation has been used widely in patients with difficult airways. Their routine use, however, is not widely practiced. This review will summarize some of the newly available devices to assist tracheal intubation, with their advantages and disadvantages when compared with conventional laryngoscopes. It also presents the reasons to support their use in both elective and emergency airway management. PMID- 27276778 TI - UPPER AIRWAY BLOCKS FOR AWAKE DIFFICULT AIRWAY MANAGEMENT. AB - Airway anesthesia is pivotal for successful awake intubation provided either topically or by blocks. Airway blocks are considered technically more difficult to perform and carry a higher risk of complications. However, in experienced hands, they can be useful as they provide excellent intubating conditions. For complete upper airway anesthesia, bilateral glossopharyngeal and superior laryngeal nerve blocks with translaryngeal injection are required. Superior laryngeal nerve block and translaryngeal injection can be performed easily, safely and with a high success rate in patients with normal anatomy. In those with difficult landmarks, ultrasound can be of assistance. For the superior laryngeal nerve block, other targets than the nerve itself must be established to make the technique consistently successful, easy to teach, learn and perform. The same applies to the translaryngeal injection, where the use of ultrasound is necessary for correct midline identification. Intraoral glossopharyngeal nerve block is also safe and easy to perform, but associated with long lasting discomfort. Bilateral extraoral peristyloid approach should be discouraged since inadvertent blocks of the closely adjacent vagus nerve cannot be prevented in this location. A safe and easy method of blocking the distal portions of the glossopharyngeal nerve for awake intubation is therefore required. PMID- 27276779 TI - AIRWAY MANAGEMENT WITH DIRECT LARYNGOSCOPY IN A CHILD WITH GOLDENHAR SYNDROME. AB - Goldenhar syndrome, also known as oculoauriculovertebral dysplasia, is a rare congenital condition characterized by facial, cranial, vertebral, ocular, auricular and cardiac abnormalities. This syndrome is associated with hemifacial microsomia due to inadequate growth of the mandible and vertebral anomaly of the cervical part of the spine. For anesthesiologists, airway management is of great interest because of facial and oral abnormalities such as mandibular hypoplasia and limitation of neck movement. Considering different conditions of Goldenhar syndrome, every patient should be preoperatively evaluated in order to make the plan for the anticipated difficult airway management. We report a case of a 2.5 year-old boy undergoing palatoplasty, who required general anesthesia and orotracheal intubation. Our decision to intubate with direct laryngoscopy and with slight external pressure on the larynx proved successful. PMID- 27276780 TI - MOEBIUS SYNDROME: CHALLENGES OF AIRWAY MANAGEMENT. AB - Moebius syndrome is a rare nonprogressive congenital neurological disorder with a wide range of severity and variability of symptoms. This diversity is a consequence of dysfunction of different cranial nerves (most often facial and abducens nerves), accompanying orofacial abnormalities, musculoskeletal malformations, congenital cardiac diseases, as well as specific associations of Moebius and other syndromes. The authors present anesthesia and airway management during the multiple tooth extraction surgery in a 10-year-old girl with Moebius syndrome associated with Poland and trigeminal trophic syndromes. PMID- 27276781 TI - BILATERAL PNEUMOTHORAX AS A COMPLICATION OF PERCUTANEOUS TRACHEOSTOMY: CASE REPORT. AB - Percutaneous dilatational tracheostomy is a common surgical procedure that is becoming the method of choice in critically ill patients whenever prolonged airway secure and/or ventilation support is needed. Although adverse events are relatively uncommon, serious life threatening complications can arise from this bedside procedure. We report a case of a 70-year-old female who developed extensive subcutaneous emphysema and bilateral pneumothorax immediately after a percutaneous dilatational tracheostomy procedure. Different mechanisms, such as damage to posterior or anterior tracheal wall, false passage or paratracheal placement or dislocation of the cannula are considered to be responsible for the development of pneumothorax and subcutaneous emphysema. Although bronchoscopic control after the tracheostomy procedure did not reveal any tracheal injury, we believe that subcutaneous emphysema and bilateral pneumothorax are most likely caused by procedure induced injuries of the trachea in addition to the applied high airway pressure induced by excessive or inappropriate ventilation. In our case report, we would like to emphasize that continuous bronchoscopic guidance during percutaneous tracheostomy is invaluable in decreasing the incidence of its overall complications, especially during enhancing the team experience. PMID- 27276782 TI - ANESTHETIC MANAGEMENT OF A PATIENT WITH CENTRAL AIRWAY COMPRESSION DUE TO POSTERIOR MEDIASTINAL MASS. AB - Patients with mediastinal masses present unique challenge to anesthesiologists. Patients with anterior mediastinal masses have well documented cases of respiratory or cardiovascular collapse during anesthesia and in postoperative period. Masses in the posterior mediastinum have been traditionally regarded to carry a significantly lower risk of anesthesia related complications but cases of near fatal cardiorespiratory complications have been reported. We describe anesthetic management of a patient with posterior mediastinal mass compressing the trachea and the left main bronchus presented for left thoracotomy and tumor excision. The patient experienced pain and cough, and exhibited positional dyspnea. Airway was successfully secured with awake nasotracheal intubation and placement of single lumen endobronchial tube. PMID- 27276783 TI - LARYNGEAL CHONDROSARCOMA: SUCCESSFUL USE OF VIDEO LARYNGOSCOPE IN ANTICIPATED DIFFICULT AIRWAY MANAGEMENT. AB - Laryngeal chondrosarcoma is a rare mesenchymal tumor, most frequently affecting cricoid cartilage. The objective of this report is to present successful video laryngoscope usage in a patient with anticipated difficult airway who refused awake fiberoptic endotracheal intubation (AFOI). A 59-year-old male patient was admitted in our hospital due to difficulty breathing and swallowing. On clinical examination performed by ENT surgeon, preoperative endoscopic airway examination (PEAE) could not be performed properly due to the patient's uncooperativeness. Computed tomography revealed a spherical tumor that obstructed the subglottic area almost entirely. Due to the narrowed airway, the first choice for the anticipated difficult airway management was AFOI, which the patient refused. Consequently, we decided to perform endotracheal intubation with indirect laryngoscope using a C-MAC video laryngoscope (Karl Storz, Tuttlingen, Germany). Reinforced endotracheal tube (6.0 mm internal diameter) was placed gently between the tumor mass and the posterior wall of the trachea in the first attempt. Confirmation of endotracheal intubation was done by capnography. In a patient with subglottic area chondrosarcoma refusing PEAE and AFOI, video laryngoscope is a particularly helpful device for difficult airway management when difficult airway is anticipated. PMID- 27276784 TI - Making Lives better. PMID- 27276786 TI - Government injects L200m to social care programme. PMID- 27276785 TI - Scotland charities demand urgent action for 5,000 homeless children. PMID- 27276787 TI - Interface communities most linked to sectarian violence and deprivation. PMID- 27276788 TI - Breastfeeding reduces ear infections, study shows. PMID- 27276789 TI - Research sheds light on type 2 diabetes origin. PMID- 27276791 TI - Health visitor numbers appear to drop amid data collection confusion. PMID- 27276790 TI - Twenty-year survival expected for majority of liver transplant children. PMID- 27276792 TI - Make sure you're connected. PMID- 27276793 TI - Downbanding: in a CNN's shoes. PMID- 27276794 TI - BREAKING BOUNDARIES. PMID- 27276795 TI - Breathe easy. PMID- 27276796 TI - An urgent need. PMID- 27276797 TI - Recognition and management of learning disabilities in early childhood by community practitioners. PMID- 27276798 TI - Attachment icebergs: Maternal and child health nurses' evaluation of infant caregiver attachment. AB - Secure attachment of infants to their caregiver is important when promoting the emotional wellbeing and mental health of infants. Maternal and child health (MCH) nurses are well positioned to observe the quality of interactions between infants and caregivers and to assess and intervene. However, as yet there are no approved methods to assess the emotional and mental health of infants in community settings. A qualitative descriptive study of 12 MCH nurses in Victoria, Australia, using semi-structured interviews, was thematically analysed. The data revealed that nurses used many skills to identify and manage attachment difficulties. Key among these were observations of interactions, collaboration with caregivers and reflective practice. Assessments and interventions are also influenced by nurses' emotions, attitudes and workplace factors. An unexpected finding was that attachment markers can be likened to an 'iceberg': warning indicators at the tip can be easily observed by the nurse, while the less obvious underlying factors need to be explored in order to support attachment and improve infant mental health outcomes. Education for nurses should include concepts of attachment and link behaviours with emotional wellbeing. PMID- 27276799 TI - Health visitors have much to offer pre-registration child branch student nurses. AB - The primary care workforce has recently become the focus of several reports, which highlight the preparation and upskilling of nurses for a move to acute care in the community and plans to widen the community and primary care workforce. This paper explores current health plans in relation to pre-registration nurse education and identifies the health visitor as having key qualities and skills to manage child branch student nurses' community placements. A health visitor's perspective reinforces the discussion and highlights how the current climate offers a valuable opportunity for health visitors to promote a positive learning environment. Numerous learning opportunities are identified in the community placement, which can serve to equip student nurses with key nursing and interprofessional skills, such as leadership, management, assessment, communication and negotiation. A student's perspective is offered to provide an example of how a positive experience in the community can enhance student learning. This discussion concludes that the health visitor can be a valuable mentor to offer pre-registration student nurses a supportive environment in which to identify their strengths and weaknesses, and encourage students to flourish as caring and compassionate nurses. PMID- 27276800 TI - Last word with ... SHIRLEY SMITH. PMID- 27276801 TI - [OBSERVATION OF EFFECTIVENESS OF HIP RESURFACING ARTHROPLASTY IN TREATMENT OF OSTEONECROSIS OF FEMORAL HEAD IN YOUNG AND MIDDLE-AGED PATIENTS]. AB - OBJECTIVE: To evaluate the clinical and radiographic outcomes of hip resurfacing arthroplasty (HRA) for treating osteonecrosis of the femoral head (ONFH) in young and middle-aged patients. METHODS: Between January 2008 and April 2009, 34 patients with ONFH underwent HRA. There were 19 males and 15 females with an average age of 54 years (range, 33-59 years). Of 34 cases, 16 left hips and 18 right hips were involved, including 9 cases of alcohol-induced ONFH, 8 cases of steroid-induced ONFH, 7 cases of traumatic ONFH, and 10 cases of unexplained ONFH. According to modified Ficat classification system, 26 hips were rated as stage III, and 8 hips as stage IV. The Harris hip score (HHS) and modified University of California, Los Angeles (UCLA) activity score were used to evaluate the clinical results. Migration of prosthesis was assessed on the anteroposterior radiographs. The abduction angle was measured on the acetabular side. On the femoral side, varus-valgus shift was determined by measurement of stem-shaft angle. The axial collapse of femoral component was assessed with the component lateral cortex ratio. RESULTS: Healing of incision by first intention was achieved in all patients without complications of infection and thrombosis of deep vein of lower extremities. Thirty-two patients were followed up 78 months on average (range, 70-84 months). No implant loosening, infection, femoral neck fracture, dislocation, and inflammatory pseudotumor were observed. At last follow up, the HHS score was significantly increased to 95.22 +/- 1.47 from preoperative 50.10 +/- 2.27 (t=1.510, P=0.008). Modified UCLA activity score was significantly increased to 7.70 +/- 1.13 from preoperative 3.90 +/- 0.90 (t=0.830, P=0.003). The abduction angle, stem-shaft angle, and compotent-lateral cortex ratio showed no significant difference between at 3 days after operation and last follow-up (P>0.05). CONCLUSION: If the indication of operation is mastered strictly, HRA may be effective in treatment for ONFH at Ficat stage III or IV in young and middle-aged patients. PMID- 27276802 TI - [CLINICAL STUDY OF INTERNAL TENSION-RELIEVING TECHNIQUE IN ARTHROSCOPIC ASSISTED ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION]. AB - OBJECTIVE: To study the effectiveness of internal tension-relieving technique for arthroscopic assisted anterior cruciate ligament (ACL) reconstruction. METHODS: Between March 2011 and September 2014, 51 cases of complete ACL rupture were randomly divided into 2 groups. Arthroscopic assisted single-bundle ACL reconstruction combined with internal tension-relieving technique was performed in 26 cases (group A), arthroscopic assisted single-bundle ACL reconstruction in 25 cases (group B). There was no significant difference in gender, age, cause of injury, injured side, body mass index, Outerbridge classification of articular cartilage injury, disease duration, and the preoperative International Knee Documentation Committee (IKDC) score, Lysholm score, and KT-1000 test value between 2 groups (P>0.05). At 3, 6, and 12 months after operation, the KT-1000 was used to measure the anterior stability, and IKDC and Lysholm scores to evaluate the function of knee joint. RESULTS: Healing of incision by first intention was obtained in all patients of 2 groups, without complications of infection, deep vein thrombosis of lower extremity, and blood vessels and nerves injury. The patients were followed up 12 months after operation. All patients received second microscopic examination. The reconstructed ACL had good continuity and good coverage of synovial tissue. There was no re-rupture in any cases. The range of motion of the knee joint was close to normal. The MRI showed good healing of the ligament and the bone tunnel at 12 months after operation. KT 1000 test value, IKDC score, and Lysholm score at 3, 6, and 12 months after operation were significantly improved when compared with preoperative ones (P<0.05), but no significant difference was found among different time points after operation (P>0.05). There was no significant difference in IKDC score and Lysholm score between 2 groups at 3 and 12 months (P>0.05); but IKDC score and Lysholm score of group A were significantly higher than those of group B (P<0.05) at 6 months. At diffenent time points after operation, the KT-1000 test values of group A were significantly lower than those of group B (P<0.05) except the value at 3 months (P>0.05). CONCLUSION: For patients with ACL rupture, using internal tension-relieving technique can effectively alleviate tension force of reconstructed ligament, which is beneficial to the healing of reconstructed ligament and early rehabilitation of the knee joint. PMID- 27276803 TI - [EFFECTIVENESS OF SLIDING OSTEOTOMY FOR CORRECTING SEVERE VALGUS DEFORMITY IN TOTAL KNEE ARTHROPLASTY]. AB - OBJECTIVE: To explore the surgical technique and effectiveness of sliding osteotomy of medial femur condyle in handling soft tissue balance of severe valgus deformity in total knee arthroplasty (TKA). METHODS: Between June 2008 and February 2014, 18 cases (19 knees) of severe valgus knees undergoing sliding osteotomy of medial femur condyle in primary TKA were included, Of the 18 patients, 6 were male and 12 were female with an average age of 52.3 years (range, 29-72 years), including 3 cases (3 knees) of osteoarthritis, 11 cases (12 knees) of rheumatoid arthritis, 3 cases (3 knees) of post-traumatic arthritis, and 1 case (1 knee) of deformities in skeletal dysplasia. Before surgery, the tibial femur angle (TFA) was (33.0 +/- 2.9) degrees; the Hospital for Special Surgery (HSS) score was 41.6 +/- 7.7; the Knee Society Score (KSS) lateral stability score was 6.0 +/- 5.4. All cases wererated as type II according to Krackow classification of valgus knee. During primary TKA, sliding osteotomy of medial femur condyle was performed via a medial parapatellar approach. RESULTS: Incision healed by first intention in all cases. Peroneal nerve palsy occurred in 1 patient, which was cured after 6 months of conservative treatment. Eighteen cases were followed up 19 months to 7 years, with an average of 5.7 years. All patients had no complications of deep vein thrombosis, deep infection, and prosthesis loosening. X-ray films showed that bone healing was achieved in all cases at 6 months. At last follow-up, the TFA was (4.8 +/- 1.8) degrees, showing significant difference when compared with preoperative value (t=62.61, P=0.00). The HSS score was 87.2 +/- 10.5 and the KSS lateral stability score was 12.4 +/- 3.1, all showing significant differences when compared with preoperative scores (t = -33.35, P=0.00; t = -6.83, P=0.00). CONCLUSION: Sliding osteotomy of medial femur condyle is effective for correcting severe valgus knee deformity during TKA. Satisfactory joint function and stability may be achieved PMID- 27276804 TI - [SEMITENDINOUS AND GRACILIS TRANSFER FOR TREATMENT OF MEDIAL COLLATERAL LIGAMENT INJURY CAUSED BY TOTAL KNEE ARTHROPLASTY]. AB - OBJECTIVE: To evaluate the effectiveness of semitendinous and gracilis transfer for the treatment of medial collateral ligament (MCL) injury caused by total knee arthroplasty (TKA). METHODS: Between March 2009 and May 2014, 11 patients (11 knees) with MCL injuries caused by primary TKA were treated by semitendinous and gracilis transfer in primary TKA (injury group). Another 18 patients (21 knees) without MCL injury were included as the control group. There was no significant difference in gender, age, injury sides, disease duration, body mass index, knee varus deformity, and preoperative Knee Society Score (KSS) between 2 groups (P>0.05), with comparability. KSS score was used to evaluate the function after operation. RESULTS: Primary healing of incision was obtained in all patients, and no complications of joint instability and pain occurred. The follow-up time was-6 29 months in injury group and was 7-34 months in control group. At last follow up, the KSS clinical score and ftinctional score were significantly increased to 89.82 +/- 3.76 and 89.54 +/- 3.50 in the injury group (P<0.05) and were significantly increased to 90.19 +/- 3.39 and 90.00 +/- 3.53 in the control group (P<0.05) respectively, but no significant difference was shown between 2 groups (t=0.158, P=0.877; t=0.820, P=0.432). X-ray films showed no prosthetic loosening or subsidence during follow-up. CONCLUSION: The semitendinous and gracilis transfer is reliable for the treatment of MCL injury caused by TKA. The insertions of semitendinous tendon and gracilis are close to that of the knee MCL, which can effectively improve knee function. PMID- 27276805 TI - [EFFECTIVENESS COMPARISON OF PROXIMAL FEMORAL NAIL ANTI-ROTATION IN SUPINE "SCISSORS" POSITION AND IN LITHOTOMY POSITION TO TREAT FEMORAL INTERTROCHANTERIC FRACTURES OF OLD PATIENTS]. AB - OBJECTIVE: To compare the effectiveness of proximal femoral nail anti-rotation (PFNA) between in the supine "scissors" position and in the lithotomy position for treating femoral intertrochanteric fractures of old patients. METHODS: A retrospective study was performed on 58 patients with femoral intertrochanteric fractures treated with PFNA between January 2013 and January 2015. Fracture was treated with PFNA in the lithotomy position in 28 cases (group A) and in the supine "scissors" position in 30 cases (group B). There was no significant difference in gender, age, side, cause of injury, fracture type, and interval from injury to operation between 2 groups (P>0.05). The incision length, operation time, perspective times, intraoperative blood loss, complications, and fracture healing time were recorded; Harris hip score was used to access the effectiveness. RESULTS: The wound healed by first intention without infection, pressure sores, deep vein thrombosis of lower extremity, and other complications. There was no significant difference in incision length between 2 groups (t=1.313, P=0.212). Group B was significantly better than group A in operation time, perspective times, and intraoperative blood loss (P<0.05). All patients were followed up 10-31 months (mean, 15.3 months). Stretch injury at normal side and perineal discomfort occurred in 1 case and 5 cases of group A respectively, and no nonunion and other complications was observed in the other patients. There was no significant difference in fracture healing time and Harris hip score at last follow-up between 2 groups (P>0.05). CONCLUSION: PFNA in the supine "scissors" position has exact effectiveness and advantages of shorter operation time, less intraoperative blood loss, less perspective times, and fewer complications. PMID- 27276806 TI - [PRELIMINARY APPLICATION OF THREE-DIMENSIONAL PRINTING PERSONALIZED EXTERNAL FIXATOR IN SERIOUS TIBIOFIBULA FRACTURES]. AB - OBJECTIVE: To explore a new method of treating serious tibiofibula comminuted fracture by using three-dimensional (3-D) printing personalized external fixator. METHODS: In April 2015, a male patient (aged 18 years with a height of 171 cm and a weight of 67 kg) with left tibiofibula comminuted fracture was included in the study. Computer-assisted reduction technique combined with 3-D printing was used to develop a customised personalized external fixator for fracture reduction. The effectiveness was observed. RESULTS: The operation time was about 10 minutes without fluoroscopy, and successful reduction was obtained. The patient had equal limb length after operation. X-ray films showed that the posterior angulation of distal fracture was corrected 37 degrees, and the eversion angle was corrected 4 degrees. The tibial fractures had good paraposition or alignment, and the lower limb force line was corrected completely. No new fracture displacement occurred. The clinical healing time of fracture was 3.5 months and the bone union was achieved after 8 months. The function of affected limb recovered well after operation. CONCLUSION: A personalized external fixator for serious tibiofibula comminuted fracture reduction made by 3-D printing technique has the merits of easy manipulation, high individuation, accurate reduction, stable fixation, and no need of fluoroscopy. PMID- 27276807 TI - [EFFECTIVENESS OF DISTRACTION THERAPY ASSISTED BY ARTHROSCOPE IN TREATMENT OF ANKLE TRAUMATIC OSTEOARTHRITIS]. AB - OBJECTIVE: To investigate the effectiveness of distraction therapy assisted by arthroscope in the treatment of ankle traumatic osteoarthritis. METHODS: Between October 2013 and October 2014, 13 patients with anlde traumatic osteoarthritis were treated, including 8 males and 5 females with an age range of 44-63 years (mean, 55.2 years). The left ankle and the right ankle were involved in 4 and 9 cases respectively. The disease duration was 1.5-10.0 years (median, 5 years). The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hind foot scale score was 51.00 +/- 7.09; the short-form 36 health survey scale (SF-36) score was 40.82 +/- 4.62. According to Scranton grade system, 9 cases were rated as grade II and 4 cases as grade III. First, ande hyperplasia osteophytes was removed under arthroscope, then Ilizarov apparatus was used to maintain distraction of 5 10 mm ande space for 3 months. RESULTS: One case had postoperative pin tract infection after removing the external fixation, and infection was controlled by dressing treatment; no related complications occurred in the other patients. All patients got follow-up of 12-18 months (mean, 14.7 months). Patients achieved disappearance of ankle swelling, pain relief, and were able to walk after rehabilitation. The ankle activity was obviously improved. At last follow-up, AOFAS ankel-hind foot scale score and SF-36 score were significantly increased to 85.23 +/- 6.41 and 56.29 +/- 6.20 respectively (t=20.756, P=0.025; t=11.647, P=0.018). According to AOFAS scores, the results were excellent in 4 cases, good in 8 cases, and fair in 1 case; the excellent and good rate was 92.3%. Postoperative X-ray film showed normal ankle position and alignment, osteophytes at the edges of the tibia and talus, articular surface sclerosis, normal joint space, and no joint swelling. CONCLUSION: Distraction therapy assisted by arthroscope is an effective method for treating ankle traumatic osteoarthritis. PMID- 27276808 TI - [PART-KESSLER TECHNIQUE WITH SUTURE ANCHOR IN REPAIR OF SPONTANEOUS Achilles TENDON RUPTURE]. AB - OBJECTIVE: To summarize the application and experience of repairing spontaneous Achilles tendon rupture by part-Kessler technique with suture anchor. METHODS: Between January 2011 and December 2013, 31 patients with spontaneous Achilles tendon rupture were treated by part-Kessler technique with suture anchor. Of 31 cases, 23 were male and 8 were female, aged 16-53 years (mean, 38 years). The left side was involved in 15 cases and the right side in 16 cases. The causes of injury included sudden heel pain and walking weakness during sports in 22 cases; no surefooted down-stairs, slip, and carrying heavy loads in 9 cases. The distance from broken site to the calcaneus adhension of Achilles tendon was 3-6 cm (mean, 4.2 cm). The time from injury to operation was 7 hours to 4 days (mean, 36.8 hours). RESULTS: All incisions healed by first intention without nerve injury or adhering with skin. The patients were followed up 6-24 months (mean, 15 months). All patients could complete 25 times heel raising without difficulty at 6 months after operation. No Achilles tendon rupture occurred again during follow up. At 6 months after operation, the range of motion of the ankle joint in dorsiflexion and plantar flexion showed no significant difference between normal and affected sides (t=0.648, P=0.525; t=0.524, P=0.605). The circumference of the affected leg was significantly smaller than that of normal leg at 6 months after operation (t=2.074, P=0.041), but no significant difference was found between affected and normal sides at 12 months after operation (t=0.905, P=0.426). The American Orthopedic Foot and Ankle Society (AOFAS) scores at 6, 12, 18, and 24 months after operation were significantly higher than preoperative score (P<0.05); the score at 6 months after operation was significantly lower than that at other time points (P<0.05), but no significant difference was shown between the other time points (P>0.05). CONCLUSION: Repairing spontaneous Achilles tendon rupture by part-Kessler technique with suture anchor can supply strong strain and decrease the shear forces of suture. So part-Kessler technique with suture anchor is successful in repairing spontaneous Achilles tendon rupture. PMID- 27276810 TI - [ESTABLISHMENT OF A NEW RADIUS DEFECT MODEL BASED ON ULNA ANATOMICAL MEASUREMENT IN RABBITS]. AB - OBJECTIVE: To introduce a new bone defect model based on the anatomical measurement of radius and ulna in rabbits for offering a standard model for further tissue engineering research. METHODS: Fifteen healthy 4-month-old New Zealand rabbits were selected for anatomic measurement and radiological measurement of the radius and ulna. Another 30 healthy 4-month-old New Zealand rabbits were randomly divided into groups A, B, and C (n=10). The radius bone defect was created bilaterally in 3 groups. In group A, the periosteum and interosseous membranes were fully removed with jig-saw by approach between extensor carpi radialis muscle and musculus extensor digitorum. The periosteum and interosseous membranes were fully removed in group B, and only periosteum was removed in group C with electric-saw by approach between extensor carpi radialis muscle and flexor digitorum profundus based on anatomical analysis results of ulnar and radial measurement. The gross observation, X-ray, micro-CT three dimensional reconstruction, bone mineral density (BMD), and bone mineral content (BMC) were observed and recorded at immediate and 15 weeks after operation. HE staining and Masson staining were performed to observe bone formation in the defect areas. RESULTS: Blood vessel injury (1 rabbit), tendon injury (2 rabbits), postoperative hematoma (1 rabbit), and infection (1 rabbit) occurred in group A, postoperative infection (1 rabbit) in group C, and no postoperative complications in group B; the complication rate of group A (50%) was significantly higher than that of groups B (0%) and C (10%) (P<0.05). The radiological examination showed bone defects were fully repaired in groups A and B at 15 weeks, but bridging callus formation was observed in group C. There was no significant difference in BMC and BMD among 3 groups (P>0.05). HE staining and Masson staining results showed bone formation in group A, with structure disturbance and sclerosis. New bone formed in groups B and C, cartilage cells were observed in the center of bone cells. CONCLUSION: The radius bone defect model established by approach between extensor carpi radialis muscle and flexor digitorum profundus is an ideal model because of better exposures, less intra-operative blood loss, less complications. Interosseous membranes play a role in bone tissue repair process, and the mechanism needs further study. PMID- 27276809 TI - [EFFECTIVENESS OF REPAIRING OR RECONSTRUCTING DEFECTS OF FOREFOOT]. AB - METHODS: Between February 2006 and February 2013, 57 patients with defects of the forefoot were treated. There were 41 males and 16 females with an average age of 38.9 years (range, 19-68 years). The disease causes included motor vehicles crush injury in 28 cases, crashing injury in 17 cases, and machine extrusion injury in 12 cases. The left side was involved in 25 cases and the right side in 32 cases, with a mean disease duration of 4.7 hours (range, 0.5-75.0 hours). Defect located at the 1st metatarsus in 9 cases, at the 5th metatarsus in 8 cases, at the 1st and the 2nd metatarsus in 16 cases, at the 4th and 5th metatarsus in 11 cases, at multiple metatarsus and the forefoot in 13 cases. The bone defect ranged from 2.5 cm x 1.9 cm x 1.4 cm to 13.3 cm x 11.2 cm x 2.7 cm. The soft tissue defect ranged from 12.4 cm x 6.3 cm to 27.2 cm x 18.7 cm. The iliac bone or vascularized iliac bone or vascularized fibula bone was used to rebuild the arch of the foot, and free flap was used to repair defects of the forefoot. The donor site was sutured directly or covered with skin graft. RESULTS: Venous crisis and partial necrosis occurred in 3 and 2 flaps respectively, which healed after symptomatic treatment. The other flaps and grafted skins survived, and wounds healed primarily. Fifty one cases were followed up 1.5-2.5 years (mean, 2.1 years). The appearance was excellent and the feeling of the flap recovered at different levels. The two point discrimination was 8.4-19.8 mm (mean, 13.7 mm) at 1.5 years after operation. According to upper extremity functional evaluation standard by hand surgery branch of Chinese Medical Association, sensation recovered to 52 in 6 cases, to 53 in 18 cases, and to 54 in 27 cases. The patients began to walk with weight loading at 2-6 months after operation (mean, 3.9 months). The bone healing time was 3-6 months (mean, 4.2 months). Based on American Orthopaedic Foot and Ankle Society (AOFAS) standards, the results were excellent in 19 cases, good in 24 cases, fair in 7 case, and poor in 1 case, and the excellent and good rate was 84.3%. CONCLUSION: It is a good solution to treat defects of the forefoot to use iliac bone or vascularized iliac bone or vascularized fibula bone for rebuilding the arch of the foot and use free flap for repairing defect. PMID- 27276811 TI - [EFFECT OF SPINAL DURAL RELEASE ON TREATMENT OF MULTI-SEGMENTAL CERVICAL MYELOPATHY WITH OSSIFICATION OF POSTERIOR LONGITUDINAL LIGAMENT BY CERVICAL LAMINOPLASTY]. AB - OBJECTIVE: To explore the effect of spinal dural release on the effectiveness of expansive cervical laminoplasty for treating multi-segmental cervical myelopathy with ossification of posterior longitudinal ligament. METHODS: A retrospective analysis was made on the clinical data of 32 patients with multi-segmental cervical myelopathy with cervical ossification of posterior longitudinal ligament who underwent expansive cervical laminoplasty and spinal dural release between February 2011 and October 2013 (group A); and 36 patients undergoing simple expansive cervical laminoplasty between January 2010 and January 2011 served as controls (group B). There was no significant difference in gender, age, disease duration, affected segments, combined internal disease, preoperative cervical curvature, Japanese Orthopaedic Association (JOA) score, and visual analogue scale (VAS) score between 2 groups (P>0.05). Postoperative JOA score and improvement rate, VAS score, posterior displacement of the spinal cord, and the change of cervical curvature were compared between 2 groups. RESULTS: Spinal dural tear occurred in 3 cases (2 cases in group A and 1 case in group B) during operation. Cerebrospinal fluid leakage occurred in 3 cases (2 cases in group A and 1 case in group B) after operation. The patients were followed up 12-46 months (mean, 18.7 months). At last follow-up, the JOA score and VAS score were significantly improved in 2 groups when compared with preoperative scores (P<0.05). JOA score and improvement rate of group A were significantly higher than those of group B (P<0.05), but VAS score of group A was significantly lower than that of group B (P<0.05). At last follow-up, no significant difference in cervical curvature was found between 2 groups (P>0.05); posterior displacement of the spinal cord of group A was significantly larger than that of group B (P<0.05). No reclosed open-door was observed during follow-up. CONCLUSION: For patients with multi-segmental cervical myelopathy with ossification of posterior longitudinal ligament, full spinal dural release during expansive cervical laminoplasty can increase the posterior displacement of spinal cord, and significantly improve the effectiveness. PMID- 27276812 TI - [COMBINED POSTERIOR AND ANTERIOR APPROACHES FOR RESECTION OF THORACOLUMBAR SPINAL HUGE DUMBBELL-SHAPED TUMOR]. AB - OBJECTIVE: To investigate the surgical outcome of combined posterior and anterior approaches for the resection of thoracolumbar spinal canal huge dumbbell-shaped tumor. METHODS: Between January 2009 and March 2015, 12 patients with thoracolumbar spinal canal huge dumbbell-shaped tumor were treated by posterior approach and anterolateral approach through diaphragmatic crura and thoracoabdominal incision for complete resection. There were 9 males and 3 females, with an average age of 45 years (range, 30-65 years). The disease duration was 8-64 weeks (mean, 12.7 weeks). The tumor was located at T(12), L1 in 6 cases, at L(1,2) in 5 cases, and at L(2,3) in 1 case. The tumor size ranged from 4.3 cm x 4.0 cm x 3.5 cm to 7.5 cm x 6.3 cm x 6.0 cm. According to tumor outside the spinal involvement scope and site and based on the typing of Eden, 5 cases were rated as type b, 2 cases as type d, 4 cases as type e, and 1 case as type f in the transverse direction; two segments were involved in 8 cases, and more than two segments in 4 cases. The degree of tumor excision, tumor recurrence, and the spine stability were observed during follow-up. The verbal rating scale (VRS) was used to evaluate pain improvement. RESULTS: The average surgical time was 170 minutes (range, 150-230 minutes); the average intraoperative blood loss was 350 mL (range, 270-600 mL). All incisions healed by first intention, and no thoracic cavity infection and other operation related complication occurred. Of 12 cases, 10 were histologically confirmed as schwannoma, and 2 as neurofibroma. The patients were followed up 6 months to 6 years (mean, 31 months). Neurological symptoms were significantly improved in all patients, without lower back soreness. The thoracolumbar X-ray film and MRI showed no tumor residue. No tumor recurrence, internal fixator loosening, scoliosis, and other complications were observed during follow-up. VRS at last follow-up was significantly improved to grade 0 (10 cases) or grade 1 (2 cases) from preoperative grade 1 (2 cases), grade 11 (8 cases), and grade III (2 cases) (Z = -3.217, P=0.001). CONCLUSION: Combined posterior approach and anterolateral approach through diaphragmatic crura and thoracoabdominal incision for complete resection of thoracolumbar spinal canal huge dumbbell-shaped tumor is feasible and safe, and can protect the stability of thoracolumbar spine and paraspinal muscle function. It can obtain satisfactory clinical result to use this method for treating the complex type of thoracolumbar spinal canal dumbbell-shaped tumor. PMID- 27276813 TI - [CLASSIFICATION AND TREATMENT STRATEGIES OF SYMPTOMATIC SEVERE OSTEOPOROTIC VERTEBRAL FRACTURE AND COLLAPSE]. AB - OBJECTIVE: To investigate the classification and treatment strategies of symptomatic severe osteoporotic vertebral fracture and collapse. METHODS: Between August 2010 and January 2014, 42 patients with symptomatic severe osteoporotic vertebral fracture and collapse were treated, and the clinical data were retrospectively analyzed. According to clinical symptom and imaging materials, 23 cases were classified as type I (local pain, limitation of motion, no neurological symptom, and no obvious deformity), 12 cases as type II (slight neurological symptom and kyphotic Cobb angle < or = 30 degrees), and 7 cases as type III (severe neurological symptom and kyphotic Cobb angle >30 degrees). In 23 type I patients, 17 underwent percutaneous vertebral augmentation, 6 underwent posterior pedicle screw fixation strengthened with bone cement combined with percutaneous vertebral augmentation. In 12 type II patients, they were treated with local spinal decompression and internal fixation strengthened with bone cement. In 7 type III patients, 5 underwent posterior osteotomy, and 2 underwent one stage posterior approach of vertebral resection and reconstruction. The visual analogue scale (VAS), Oswestry disability index (ODI), and local kyphotic Cobb angle were used to evaluate the neurological function. The complications were recorded. RESULTS: The operation was successfully completed in all patients. Wound infection and ketoacidosis secondary to stress blood glucose rise occurred in 1 case of type III patients respectively, and were cured after corresponding treatment; primary healing of wound was obtained in the other patients. The patients were followed up from 6 to 36 months (mean, 11.6 months). The nerve function was improved in 17 cases, and micturition disability was observed in 2 cases. Asymptomatic cement leakage occurred in 13 cases (30.95%) (7 cases in type I, 4 cases in type II, and 2 cases in type III). No bone cement dislocation and internal fixation failure were found during follow-up. The VAS score, ODI, and the local kyphotic Cobb angle at 1 week and last follow-up were significantly improved when compared with preoperative ones (P<0.05), but no significant difference was found between at 1 week and last follow-up (P>0.05). CONCLUSION: In order to improve the effectiveness and reduce the risk and complications of operation, individualized strategies should be performed according to different types of severe osteoporotic vertebral fracture and collapse. PMID- 27276814 TI - [EFFECT OF BODY MASS INDEX ON OUTCOME OF POSTERIOR 360 DEGREES FUSION FOR SINGLE LEVEL LUMBAR DEGENERATIVE DISEASES]. AB - OBJECTIVE: To investigate the effect of body mass index (BMI) on the outcome of posterior 360 degrees fusion for single-level lumbar degenerative diseases. METHODS: A retrospective study was carried on 302 cases of single- level lumbar degenerative diseases treated with posterior 360 degrees fusion between September 2009 and September 2013. All patients were divided into 3 groups according to BMI: normal weight (BMI<24 kg/M2) in 105 cases (group A), overweight (24 kg/M2 < or = BMI < 28 kg/M2) in 108 cases (group B), and obese (BMI > or = 28 kg/m2) in 89 cases (group C). There was no significant difference in gender, age, disease duration, disease patterns, affected segments, preoperative Japanese Orthopaedic Association (JOA) score and Oswestry disability index (ODI) among 3 groups (P>0.05). The operation time, intraoperative blood loss, postoperative hospital stay, and complications were recorded. The lumbar function was assessed by JOA score and ODI at pre- and post-operation (at 3, 6, and 24 months). RESULTS: The operation time, intraoperative blood loss, and postoperative hospital stay of group C were significantly more than those of groups A and B (P<0.05), but no significant difference was found between group A and group B (P>0.05). The patients were followed up 24-45 months. Postoperative JOA score and ODI showed significant improvements in each group when compared with preoperative ones (P<0.05), but there was no significant difference among groups at each time point after operation (P>0.05). There was no significant difference in the incidence of total complications among 3 groups (chi2 = 3.288, P=0.193). The incidence of incision-related complications (infection and poor healing) in group C was significantly higher than that of groups A and B (P<0.05), but no significant difference was shown between group A and group B (P>0.05). However, there was no significant difference in cerebrospinal fluid leak, pseudarthrosis formation, and revision among 3 groups (P>0.05). CONCLUSION: Posterior 360 degrees fusion for single-level lumbar degenerative diseases can obtain good effectiveness in patients with different BMI, but patients whose BMI was > or = 28 kg/in2 have longer operation time, more intraoperative blood loss, longer hospital stay, and higher incidence of postoperative incision-related complications. PMID- 27276815 TI - [EXPERIMENTAL STUDY ON EFFECT OF THREE DIFFERENT OPERATIVE WAYS OF ANNULUS FIBROSUS INCISION ON INTERVERTEBRAL DISC BIOMECHANICAL STRENGTH]. AB - OBJECTIVE: To discuss the effect of three different ways of annulus fibrosus incision on the biomechanical strength of intervertebral disc. METHODS: A total of 30 goats underwent intervertebral disc nucleus pulposus extraction at L3,4 and 45 by the working channel in group A (n=10), by circular incision in group B (n=10), and by square incision in group C (n=10). The body weight, male and female ratio, age, intraoperative blood loss, and wound healing time were recorded and compared among 3 groups. The survival rate and wound healing situation were observed after operation. At 24 weeks after operation, the goats were sacrificed, MRI images were taken to observe the signal intensity of nucleus pulposus. The disc height of L(3,4) and L(4,5) was measured to calculate the loss of disc height; biomechanical test was used to assess the strength of the disc and anulus. Histological staining was also conducted to observe the repair effect at L(4,5). RESULTS: There was no significant difference in body weight, male to female ratio, age, intraoperative blood loss, and wound healing time among groups (P>0.05). All goats survived to the end of the experiment. MRI examination showed decreased signal intensity in 3 groups, indicating intervertebral disc degeneration. According to modified Thompson classification method, the degree of intervertebral disc degeneration of group A was significantly higher than that of groups B and C (P<0.05), but no significant difference was found between groups B and C (P>0.05). Difference was not significant in intervertebral space height before operation among 3 groups (P>0.05). But after 24 weeks, the intervertebral space height in group A was significantly higher than that in groups B and C (P<0.05), and the intervertebral space height loss in group A was significantly lower than that in groups B and C (P<0.05). The biomechanical strength in group A was also significantly higher than that in groups B and C (P<0.05), but no significant difference was found between group B and group C (P>0.05). HE and Masson staining showed good continuity of annulus fibrosus and clear layers in group A; poor continuity of annulus fibrosus and obvious scar tissues were observed in groups B and C. CONCLUSION: Application of working channel may have less destruction of annulus fibrosus, it plays a positive role in the maintenance of biomechanical strength and repair of annulus fibrosus. PMID- 27276816 TI - [APPLICATION OF SPLIT-THICKNESS SCALP GRAFT AND TEMPOROPARIETAL FASCIA FLAP IN LOW HAIRLINE AURICLE RECONSTRUCTION IN MICROTIA PATIENTS]. AB - OBJECTIVE: To investigate the application and effectiveness of split-thickness scalp graft and temporoparietal fascia flap in the low hairline auricle reconstruction in microtia patients. METHODS: Between July 2010 and April 2015, 23 patients with low hairline microtia (23 ears) underwent low hairline auricle reconstruction. There were 16 males and 7 females with the mean age of 12 years (range, 6-34 years). The left ear was involved in 10 cases, and the right ear in 13 cases. There were 18 cases of lobule-type, 4 cases of concha-type, and 1 case of small concha-type. Referring to Nagata's two-stage auricular reconstruction method, the first stage operation included fabrication and grafting of autogenous costal cartilage framework; after 6 months, second stage operation of depilation and formation of cranioauricular sulcus was performed. The split-thickness scalp was taken from the part of the reconstructive ear above hairline. The hair follicles and subcutaneous tissue layers in hair area were cut off during operation. The area of depilation and auriculocephalic sulcus were covered with temporoparietal fascia flap. Then split-thickness skin was implanted on the surface of temporoparieta fascia flap. RESULTS: All operations were successfully completed. Healing of incision by first intention was obtained, without related complication. The patients were followed up 6-20 months (mean, 12 months). The reconstructed ear had satisfactory appearance and, had no hair growth. CONCLUSION: The application of split-thickness scalp graft and temporoparietal fascia flap in low hairline auricle reconstruction in microtia patients can achieve satisfactory results. PMID- 27276817 TI - [DECOMPRESSION AND DIVERTING EFFECTS OF VASCULAR ANASTOMOSIS BASED ON DIGITAL ARTERIAL ARCH BRANCH IN REPLANTATION OF FREE FINGER-PULP]. AB - OBJECTIVE: To investigate the decompression and diverting effects of vascular anastomosis based on the digital arterial arch branch in replantation of free finger-pulp in distal phalanges. METHODS: A retrospective analysis was performed on the clinical data of 12 patients (12 fingers) who underwent free finger-pulp replantation with anastomosis of proper palmar digital artery and the palmar digital artery arch branch in the distal end between December 2004 and March 2015. Of 12 cases, 9 were male and 3 were female, aged 15-39 years with an average of 32 years. The causes of injury included cutting injury in 4 cases, crush injury in 7 cases, and avulsion injury in 1 case. The thumb was involved in 2 cases, index finger in 4 cases, ring finger in 3 cases, middle finger in 1 case, and little finger in 2 cases. The free finger pulp ranged from 1.8 cm x 1.5 cm to 2.8 cmx2.0 cm. The time from injury to operation ranged from 1.5 to 11.0 hours, with an average of 5.7 hours. No arterial arch or proper palmar digital arteriae anastomosis was excluded. RESULTS: Free finger-pulp survived in 11 cases after operation; venous crisis occurred in 1 case at 2 days after operation, and was cured after symptomatic treatment. Nine cases were followed up 6-18 months with an average of 10 months. The finger-pulp had good appearance, clear fingerprint, and soft texture. The two-point discrimination was 3.1-6.0 mm, with an average of 4.6 mm at 6 months after operation. The function of finger flexion and extension was normal. And according to upper extremity functional evaluation standard by hand surgery branch of Chinese Medical Association, the results were excellent in 7 cases, and good in 2 cases. CONCLUSION: In the replantation of amputated pulp with insufficiency of venous blood outflow, the anastomosis of digital arterial arch branch in the distal end can decompress and shunt arterial blood, adjust blood inflow and outflow, and solve the problems of insufficient quantity of the vein and venous reflux disturbance. PMID- 27276818 TI - [FREE CROIN FLAP FOR REPAIRING DEFECTS OF DONOR AFTER TOE TISSUE TRANSPLANTATION]. AB - OBJECTIVE: To discuss the effectiveness of free croin flap in repairing defects of donor after toe or feetissue flap transplantation. METHODS: Between March 2010 and May 2015, 23 cases of defects of donor after toe or feet tissue flap transplantation were repaired with free croin flap and followed up for more than 6 months, and the clinical data were retrospectively analyzed. There were 15 males and 8 females, with an age range from 17 to 52 years (mean, 25.6 years). All finger or soft tissue defects were caused by trauma. Defects were repaired in emergency operation with toe or feet tissue flap transplantation in 18 cases, defects were secondarily reconstructed at 3-8 months after injury in 5 cases. The defect area at the feet donor site ranged from 3 cmx3 cm to 10 cmx6 cm, all accompanied with exposure of bone, and tendon. The area of free croin flap was 3.5 cm x 3.5 cm-11.0 cm x 6.5 cm, the vessel of flap was anastomosed with artery and vein of foot. The inguinal donor site was sutured directly. RESULTS: The operation time was 3-9 hours (mean, 4.5 hours); the intraoperative blood loss was 50-300 mL (mean, 120 mL). Vessel crisis occurred in 1 case postoperatively; mild and moderate swelling occurred in 3 cases, with small sporadic blisters formation; free croin flap survived completely in the other cases, and primary healing was obtained at feet wound and inguinal donor sites. Twenty-three cases were followed up 6-24 months (mean, 9 months). The color and texture of the croin flaps were similar to that of the adjacent skin, no obvious scar contracture and pigmentation were observed; the patient could walk with weight loading, the two point discrimination was 18-35 mm (mean, 26 mm) at 6 months after operation. The color, texture, and shape of reconstructed finger was good; the function of grasping and pinching recovered well; the two-point discrimination was 5.5-11.0 mmfunctional evaluation standard by Chinese Medical Association, the results were excellent in 18 cases and good in 5 cases. CONCLUSION: Free croin flap can effectively repair skin and soft tissue defects of donor after toe or feet tissue flap transplantation, and good function and appearance of feet can be obtained. PMID- 27276819 TI - [AN EXPERIMENTAL STUDY ON REPAIR OF FULL THICKNESS SKIN WOUND WITH GRAFT OF AUTOLOGOUS KERATINOCYTE SUSPENSION IN RATS]. AB - OBJECTIVE: To investigate the application of autologous keratinocyte suspension transplantation in skin reconstruction. METHODS: Forty adult Sprague Dawley rats (weighing, 210-230 g) were randomly divided into 4 groups (n=10): high density keratinocyte suspension transplantation (1X106 cells/cm2) group (group A), middle density (1 x 10(5) cells/cm2) group (group B), low density (1 x 10(4) cells/cm2) group (group C), and control group (group D). Skin samples were harvested from the rats in groups A, B, C for the isolation of keratinocytes. The model of anti contracture of full thickness skin wound was made in rats and autologous keratinocyte suspension was transplanted into the wound. The wound was covered by the allogeneic skin (allogeneic skin derived from Wistar rats). The survival of rats was observed after operation. The survival of allogeneic skin was observed at 7, 14, and 21 days after operation, and wound healing rate was calculated after allogeneic skin dropped off. Histological staining and immunohistochemical staining were carried out at 21 days after operation. RESULTS: All the rats survived to the end of the experiment. The allograft skins survived in all groups, dried and dropped off. The epithelium sheet could be seen in groups A and B at 21 days, a few very thin epithelium in group C, and no epithelization in group D. The wound healing rate of groups A (62.9% +/- 9.6%) and B (64.2% +/- 9.1%) were significantly higher than that of groups C (38.5% +/- 5.7%) and D (22.7% +/- 5.5%) (P<0.05), and significant difference was found between groups C and D (P<0.05), but there was no significant difference between groups A and B (P>0.05). The results of histological observation showed that squamous epithelial cells were observed in groups A, B, and C, but not in group D; obvious layers of epidermis were observed in groups A and B, thin epidermis and inflammatory cell infiltration in group C, and granulation tissue in group D. The immunohistochemistry staining showed that the expressions of collagen type IV and collagen type VII in groups A, B, and C; the percentage of collagen type IV and collagen type VII positive cells in groups A and B were significantly higher than that of group C (P<0.05), but there was no significant difference between groups A and B (P>0.05). The expressions of collagen type IV and collagen type VII in group D were negative. CONCLUSION: The repair of full thickness skin wound with graft of autologous keratinocyte suspension can achieve reconstruction of the skin. The appropriate density of keratinocyte suspension for wound healing is 1 x 10(5) cells/cm2. PMID- 27276820 TI - [CYSTECTASY AND REHABILITATION TRAINING FOR TREATMENT OF NEUROGENIC BLADDER DYSFUNCTION WITH HYPERREFLEXIA]. AB - OBJECTIVE: To investigate the effectiveness of ileal mucosal seromuscular patch for bladder expansion combined with rehabilitation training for treating neurogenic bladder dysfunction (NBD) with hyperreflexia. METHODS: A retrospective study was performed on the clinical data of 61 patients with NBD and hyperreflexia who were treated and followed up between July 2008 and June 2013. There were 36 males and 25 females, aged 6-23 years (mean, 10 years). The reasons included meningomyelocele operation (43 patients),surgery for lipoma in lumbar vertebra (4 patients), operation of thoracolubar teratoma (2 patients), and lumbosacral spina B3ifida (12 patients). The results of urodynamics indicated that bladder volume decreased obviously and the residual urine increased. The voiding cystourethrography (VCUG) showed the vesicoureteral reflux (VUR), including 6 cases (10 sides) of grade V, 7 cases (12 sides) of grade IV, and 6 cases (8 sides) of grade III. The color doppler ultrosound showed mild hydronephrosis in 23 cases (41 sides), moderate hydronephrosis in 25 cases (42 sides), and severe hydronephrosis in 13 cases (22 sides). The blood biochemical examination suggested chronic renal failure (CRF) in 13 cases. The treatment included augmentation for bladder and rehabilitation training after operation. RESULTS: The operation time was (157+/- 26) minutes; the intraoperative blood loss was (43 +/- 15) mL, and no patient was given blood transfusion. The patients were followed up 1.5-6.0 years (mean, 4.5 years). Vesical fistula occurred in 4 cases, urinary infection in 5 cases, dysuresia in 2 cases, and cystolith in 1 case after operation. At 1 year after operation, the International Consultation on Incontinence Questionnaire-Urinary Incontience Short Form (IQ-F) score was significantly better than peoperative score (H=9.813, P=0.000). The aurdynmic data showed that the difference value between observed and theoretical bladder volumes, bladder compliance, residual urine volume, maximum flow rate, and maximum storage detrusor pressure were significantly better than preoperative ones (P<0.05). And the color doppler ultrasound showed mild hydronephrosis in 34 cases (56 sides), moderate hydronephrosis in 18 cases (33 sides), and severe hydronephrosis in 9 cases (16 sides). VCUG showed that bladder volume obviously increased, no contracture was observed; and VUR was improved. And renal function was improved in 13 patients with CRF. CONCLUSION: Heal mucosal seromuscular patch for bladder expansion combined with postoperative rehabilitation training has good effectiveness in treating NBD with hyperreflexia. PMID- 27276821 TI - [EXPERIMENTAL RESEARCH OF CORE FAT TRANSFER WITH DIFFERENT DIAMETERS]. AB - OBJECTIVE: To investigate the survival rate of core fat tissue with different diameters by advanced fat harvesting instrument. METHODS: Based on core fat transfer by 1 mL syringe, the fat harvesting instrument was modified with different diameters, including 4, 6, 8, and 10 mm respectively. Between May 2014 and April 2015, the fat harvesting instrument with diameters of 4, 6, 8, and 10 mm was respectively used to harvest abdominal fat in 3 of 12 patients undergoing autologous fat transplantation. The glucose transportation quantities and the fat cell viability were measured. Then 64 nude mice at the age of 3-4 weeks were randomly divided into 4 groups (groups A, B, C, and D, n=16). And 0.5 mL fat harvested with diameters of 4, 6, 8, and 10 mm was implanted into the dorsal subcutaneous space. After fat transplantation, the mice survival and the appearance at the recipient site were observed. At 1, 2, 4, and 8 weeks after fat transplantation, the grafted fat was harvested for gross, histological and immunohistochemical observations; the intact adipocytes and capillary were counted. RESULTS: The glucose transportation quantities gradually increased with increased diameter, showing significant difference among groups (P<0.05). And the fat cell viability had a rising tendency, showing significant differences when comparing groups A and B with group D (P<0.05). With the time passing by, the protuberant appearance became flat at the recipient site, but the appearance of groups C and D was better than groups A and B. Normal shape of the fat and capillary were found in groups C and D. At immediate and 1 week after fat transplantation, there was no significant difference in fat weight among 4 groups (P>0.05); the fat weight of group A was significantly less than that of groups B, C, and D (P<0.05) at 2, 4, and 8 weeks after fat transplantation, and it was significantly less in group B than groups C and D (P<0.05), but no significant difference was found between groups C and D (P>0.05). Histological and immunohistochemical observations showed better integrity of the cells, less necrosis, and higher vascular density in group D than groups A, B, and C as time extension. The adipocyte integrity of group A was significantly worse than that of other 3 groups at other time points (P<0.05) except at 1 week (P>0.05). At each time point, the capillary counting had an increasing trend with increased diameter in all groups, showing significant difference among groups (P<0.05). CONCLUSION: With diameters within 10 mm, the thicker the core fat is transferred, the better integrlity, higher vessel density, and quicker revascularization time can be predicted. So the postoperative appearance could be maintained longer. PMID- 27276822 TI - [EXPERIMENTAL RESEARCH OF DIFFERENTIATION OF HUMAN AMNIOTIC MESENCHYMAL STEM CELLS INTO LIGAMENT CELLS IN VITRO]. AB - OBJECTIVE: To discuss whether human amniotic mesenchymal stem cells (hAMSCs) possesses the characteristic of mesenchymal stem cells, and could differentiate into ligament cells in vitro after induction. METHODS: The hAMSCs were separated through enzyme digestion, and the phenotypic characteristics of hAMSCs were tested through flow cytometry. The cells at passage 3 were cultured with L DMEM/F12 medium containing transforming growth factor beta1 (TGF-beta1) + basic fibroblast growth factor (bFGF) (group A), containing hyaluronic acid (HA) (group B), containing TGF-beta1+bFGF+HA (group C), and simple L-DMEM/F12 medium (group D) as control group. The morphology changes of cells in each group were observed by inverted phase contrast microscope at 21 days after induction; the cellular activities and proliferation were examined by sulforhodamine (SRB) colorimetric method; and specific mRNA and protein expressions of ligament including collagen type I, collagen type III, and tenascin C (TNC) were measured by real-time fluorescence quantitative PCR and immunohistochemical staining. RESULTS: The flow cytometry result indicated that hAMSCs expressed mesenchymal stem cell phenotype. After 21 days of induction, the cells in groups A, B, and C grew like spindle shaped fibroblasts under inverted phase contrast microscope, and cells showed single shape, obvious directivity, and compact arrangement in group C. The SRB result indicated that the cells in each group reached the peak of growth curve at 6 days; the cellular activities of groups A, B, and C were significantly higher than that of group D at 6 days after induction. Also, the immunohistochemical staining results showed that no expressions of TNC were detected in 4 groups at 7 days; expressions of collagen type I in groups A, B, and C were significantly higher than that in group D at 7, 14, and 21 days (P<0.001); the expressions of collagen type III in groups A, B, and C were significantly higher than that in group D at 14 and 21 days (P<0.001). There was an increasing tendency with time in collagen type I of group B, in collagen type III and TNC of groups A and C, showing significant difference among different time points (P<0.001). The real time fluorescence quantitative PCR results revealed that the mRNA expressions of collagen type I and TNC in group C were significantly higher than those in groups A and B (P<0.05), and the mRNA expression of collagen type III in group B were significantly higher than that in groups A and C at 21 days (P<0.05). The mRNA expressions of collagen type I and TNC in groups A and C and mRNA expression of collagen type III in group C had an increasing tendency with time, showing significant difference among different time points (P<0.001). CONCLUSION: The hAMSCs possesses the characteristics of mesenchymal stem cells and excellent proliferation capacity. After in vitro induction, the expressions of ligament specific genes can be up-regulated and the synthesis of ligament specific proteins can be also strengthened. As a result, it can be used as one of ligament tissue engineering seed cell sources. PMID- 27276823 TI - [PHENOTYPIC CHANGES OF EPIDERMAL STEM CELLS DIFFERENTIATING INTO SWEAT GLANDS CELLS IN VITRO AND ITS MECHANISM]. AB - OBJECTIVE: To explore the phenotypic changes of epidermal stem cells (ESCs) differentiating into sweat glands cells (SGCs) in vitro and its mechanisms. METHODS: ESCs and SGCs were isolated and cultured in vitro, which were identified using immunofluorescence staining. ESCs at passage 2 were divided into 4 groups: ESCs and SGCs co-cultured by Transwell plates in group A, ESCs cultured by simply adding sweat supernatant in group B, ESCs and SGCs co-cultured on Transwell plate adding epidermal growth factor (EGF) (60 ng/mL) in group C, and ESCs and SGCs co cultured on transwell plate adding PD98059 (10 mmol/L) in group D. The inverted microscope was used for observing the morphology of ESCs, flow cytometry for detecting ESCs positive phenotype, and Western blot for exploring mitogen activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) pathway. RESULTS: The morphology observation and immunofluorescence staining suggested that cultured cells were ESCs and SGCs. The inverted phase contrast microscope observation showed that cells had similar morphological changes, with flat polygonal shape at 9 days in groups A, C, and D; cells had slow morphological change in group B, and had similar change to that of other groups at 12 days. Significant decreasing of beta1-integrin expression and increasing of carcino-embryonic antigen (CEA) expression of ESCs were observed in group A when compared with group B, which was inhibited by EGF (group C) and enhanced by PD98059 (group D), and there were significant differences among groups A, C, and D (P<0.05). High level of ERK expression was displayed in 4 groups, but it was significantly lower in group B than the other 3 groups (P<0.05). The expression of phosphorylation ERK was the highest in group A and was the lowest in group C, showing significant difference among 4 groups (P<0.05). CONCLUSION: ESCs can be induced to differentiate into SGCs with the phenotypic changes under the condition of co-cultured by Transwell plates. The MAPK/ERK pathway plays a key role in the diffrentation of ESCs into GCCs PMID- 27276824 TI - [BIOCOMPATIBILITY OF POROUS POLY LACTIC ACID/BONE MATRIX GELATIN COMPOSITE BIOMATERIALS FOR BONE REPAIR]. AB - OBJECTIVE: To evaluate the biocompatibility of poiy lactic acid/bone matrix gelatin (PLA/BMG) composite biomaterial so as to lay a foundation for bone defect repair. METHODS: Rats' MC3T3-E1 cells were cultured with leaching solution of PIJA/BMG and PLA material respectively for 7 days. The cell proliferation rate was tested by MTT and cell toxicity grading was carried out everyday. The PLA/BMG and MG3T3-E1 cells were co-cultured, the cell shape and proliferation were observed by inverted phase contrast microscope at 1, 3, and 5 days and cell adhesion by scanning electron microscope at 5 days. The PLA and PLA/BMG were implanted subcutaneously ilS Wistar rats. The histological observation was done, and the thickness of fibrous membrane, the number of inflammatory cells, and the vascularization area were measured at postoperative 2nd, 4th, and 8th week. RESULTS: The tests for cytotoxicity in vitro showed that the cell proliferation rates were over 100% and the cell cytotoxic grades were grade 0 at 1-7 days in PLA/BMG group. While in PLA group, the cell proliferation rates were less than 100% and the cell cytotoxic grades were grade 1 at 2, 4, and 7 days. After co culture of PLA/BMG and MC3T3-E1 cells, cells grew on the surface and in the pores of PLA! BMG, and the cellular morphology was triangle or polygon with abundant microvillus on the surface. After subcutaneous implantation, the rats survived to the end of experiment, and incision healed well. PLA was wrapped by connective tissue where there were a lot of lymphocytes and neutrophiic granulocytes. The cells and tissue grew slowly in PLA. The PLA! BMG materials were wrapped by utile connective tissue where there were a few inflammatory cells. The connective tissue growth was observed in the center of PLA/BMG. There was no significant difference in the thickness of fibrous membrane between 2 groups at each time point (P>0.05). The number of inflammatory cells of PLA/BMG group were significantly less than those in PLA group at 2, 4, and 8 weeks (P<0.05); the vascularization area was significantly larger than that in PLA group (P<0.05). CONCLUSION: PLA/BMG composite biomaterials prepared by super critical-CO2 technique are good in cell and tissue biocompatibilty. PMID- 27276825 TI - [RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM]. AB - OBJECTIVE: To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. METHODS: The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. RESULTS: Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini invasive approach. CONCLUSION: The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed. PMID- 27276826 TI - The Prevalence and Related Factors of Complementary and Alternative Medicine Used in Thai Breast Cancer Patients. AB - OBJECTIVE: This study's aim is to identify the prevalence and types of complementary and alternative medicine (CAM) used among Thai breast cancer patients and investigate the factors influencing the use of CAM by these patients. MATERIAL AND METHOD: We interviewed 220 Thai breast cancer patients who visited the HRH Princess Maha Chakri Sirindhorn Medical Center and the Maha Vajiralongkorn Cancer Center during the period from October 2008 to September 2010 and collected data about their socio-economic status, history of cancer treatments and complications, the cancer staging, their Quality of life (QoL) and types and reasons of CAM used. RESULTS: The prevalence of CAM usage in Thai breast cancer patients was 560 in every 1,000 patients. Factors which influenced CAM usage were; the patients' educational level, amount of income per month, the duration of the individuals' breast cancer diagnoses, menopausal status, the type of axillary surgery used in the course of their treatment, the incidences of systemic recurrence and physical components as measured by the SF-36. CONCLUSION: The results have shown that most Thai breast cancer patients used CAM for the treatment of their breast cancer and had used CAM after being diagnosed with breast cancer Healthcare providers should recognize and provide pros and cons to patients and their family if CAM were used during breast cancer treatment. PMID- 27276827 TI - Abnormal Semen in Male Partners of Infertile Couples at HRH Maha Chakri Sirindhorn Medical Center. AB - OBJECTIVE: To determine the pattern of abnormal semen and its associate factor in male partners of infertile couples. MATERIAL AND METHOD: This research was a descriptive study. The men who attended our infertility clinic during January 2008 through December 2008 were included in the present study. All of the semen samples were analysed with standard technique using the World Health Organization (1999) protocol. The associate factors for abnormal semen were collected and analyzed. RESULTS: A total of 75 men who had official semen report, sixty-four men (85.3%) were referred for primary infertility. The mean patients' age was 35.6 +/- 5.8 years. The mean duration of infertility of couples was 3.6 +/- 2.6 years. All of these subjects had abnormal semen analysis; the most common finding was astheno-teratozoospermia in 84%. Eight men (10.7%) had oligo-astheno teratozoospermia. Three men (4%) had teratozoospermia alone. The two most common associated factors were heavy exercise and alcoholic drinking. CONCLUSION: Male factor infertility shares a pivotal role in infertile couples. Combine abnormal sperm motility and morphology group was very common. Further studies need to be carried out to explore the cause of this abnormality. PMID- 27276828 TI - Occupational Risk Factors of Lymphohematopoietic Cancer in Rayong Province, Thailand. AB - BACKGROUND: The Lymphohematopoietic Cancer (LHC) incidence rate in Thailand has been rising over the past decade with unknown etiology, including Rayong province. One hypothesis of LHC risks is exposure to occupational carcinogens. OBJECTIVE: To determine the association of occupational exposure and LHC risks in Rayong province, Thailand. MATERIAL AND METHOD: This matched hospital-based case control study was conducted in a Rayong provincial hospital from September 2009 to January 2013. One LHC case was matched with four controls in gender and age, +/-5 years. Demographic data, residential factors, behavioral factors, and occupational exposure-including chemical exposure-were obtained by interviews and collected by occupational health care officers. The risk factor was analyzed by conditional logistic regression and reported in odds ratio with 95% confidence interval. RESULTS: This study found 105 LHC cases which met the inclusion criteria and were included in the study, yielding a 66% cover rate of cases reported in the database. The histology of LHC were 51 leukemia cases (47.7%), 43 lymphoma cases (42.0%), and 11 multiple myeloma cases (10.3%). The results revealed that occupational exposure to pesticide and smoke were statistically significantly associated with LHC with adjusted ORs 2.26 (95% CI 1.30-3.91) and 1.99 (95% CI = 1.13-3.51), respectively. When stratified to histological subtype of LHC by WHO 2000, leukemia was statistically significantly associated with occupational exposure to smoke, adjusted ORs 2.43 (95% CI 1.11-5.36), with occupational pesticide exposure a significant risk of lymphoma, adjusted ORs 4.69 (95% CI 2.01-10.96). However, neither fumes, wood dust, working outdoors, cleaners, contact with animals, petroleum products and chlorine; nor occupational exposure to volatile organic compounds (VOCs) such as benzene or organic solvents, were statistically significant risk factors of LHC. In addition, there were no significant risks in the demographic data, residential factors, and behavioral factors. CONCLUSION: Occupational exposure to pesticides and smoke were important occupational risks in developing LHC in Rayong province. However, the ability or power to detect this problem due to the small sample size and recall bias from the study design could not be excluded. PMID- 27276829 TI - Effects of Long-Term Alpha-mangostin Supplementation on Hyperglycemia and Insulin Resistance in Type 2 Diabetic Rats Induced by High Fat Diet and Low Dose Streptozotocin. AB - OBJECTIVE: The present study investigated the effects of long-term supplementation of alpha-mangostin (MG; a xanthone isolated from mangosteen fruit) on hyperglycemia, and insulin resistance in type 2 diabetic rats. MATERIAL AND METHOD: Type 2 diabetes (DM2) was induced in male Sprague-Dawley rats by feeding high fat diet for three weeks followed by an IP injection of low dose streptozotocin. The rats were divided into four groups: control and diabetes without or with alpha-MG supplementation (CON, DM2, CON-MG and DM2-MG group, respectively). Alpha-MG was administered by gavage feeding in the amount of 200 mg/kg BW/day for 8 or 40 weeks. Fasting blood glucose, plasma HbA1c, cholesterol, and triglyceride were determined in all groups of rats. Serum insulin, calculated HOMA-IR and Oral glucose tolerance test were also carried out. RESULTS: The results showed that both 8 and 40 weeks DM2 groups had a significant increase in fasting blood glucose, HbA1c, plasma cholesterol and triglyceride compared with their aged-match control groups. Furthermore, the serum insulin and HOMA-IR were significantly elevated in 8 weeks DM2 whereas these two parameters were significantly decreased in 40 weeks DM2 group compared with their aged-match CON groups (p < 0.001). The OGTT showed impaired glucose tolerance in DM2 groups. Interestingly, alpha-MG supplemented DM2-MG group had significantly decreased levels of fasting blood glucose, HbA1c, plasma cholesterol, triglyceride when compared with the untreated DM2 groups. Supplementation of alpha-MG for 40 weeks in DM2-MG group showed significantly increase serum insulin levels compared with that of DM2 group (p < 0.001). Moreover alpha-MG supplemented DM-MG group demonstrated a better glucose tolerance pattern which was different from that of DM2 group at both 8 weeks and 40 weeks experimental periods. CONCLUSION: Long term alpha-mangostin supplementation has anti-hyperglycemic, anti-hyperlipidemic effects and increase insulin sensitivity by improving beta-cell functions in type 2 diabetes mellitus. PMID- 27276830 TI - Extracted Anaxagorea luzonensis A. Gray Restored Impairment of Endothelium Dependent Vasorelaxation Induced by Homocysteine Thiolactone in Rat Aortic Rings. AB - OBJECTIVE: To investigate the beneficial effects of Anaxagorea luzonensis (AL) extract on homocysteine thiolactone (HTL)-induced impairment of endothelium dependent relaxation in rat aortic rings. The mechanisms involved in the effects of AL on endothelial dysfunctions by HTL are also examined. MATERIAL AND METHOD: Aortic rings from male Wistar rats were co-incubated for 90 minutes with L arginine (3 mM), a precursor of nitric oxide (NO); superoxide dismutase (SOD, 200 U/mL), a scavenger of superoxide anion; indomethacin (10 uM), a cyclooxygenase (COX) inhibitor; SC560 (10 uM), a COX-1 inhibitor; NS398 (10 uM), a COX-2 inhibitor; or SQ29548 (1 uM), a thromboxane A2 receptor antagonist in the presence of HTL (1 mM). After 90 minutes of incubation period, the rings were pre contracted with methoxamine, and then carbachol was cumulatively added to the bath. AL (1 and 3 ug/mL) was co-incubated with 1 mM HTL in the presence of N(G) nitro-L-arginine methyl ester (L-NAME, 300 uM), a NO synthase inhibitor and p hydroxymercurybenzoate (PHMB, 10 uM), a sulfhydryl group blocking agent. Changes in tension were measured using an isometric force transducer and recorded on the PowerLab. RESULTS: Endothelium-dependent vasorelaxation to carbachol was impaired after exposure of aortic rings to HTL (0.3 and 1 mM). The inhibitory effects of HTL (1 mM) on relaxant responses to carbachol were restored by L-arginine, SOD, indomethacin, SC560 and SQ29548, but not NS398. Interestingly, AL reduced impairment of vasorelaxation induced by HTL (1 mM). However, L-NAME and PHMB largely inhibited the protective effects of AL. CONCLUSION: These results suggest that HTL-induced impairment of endothelium-dependent vasorelaxation may occur via decreased NO release, and generation of oxygen free radical. This study first shows that enhancement of TxA2 production via COX-1 pathway is involved in HTL induced endothelial dysfunctions. The protective effects of AL on impairment of relaxation by HTL may be related to increasing NO production and sulfhydryl dependent. PMID- 27276831 TI - Level of Confidence in the 12 Roles of Medical Teacher. A Descriptive Study at Faculty of Medicine, Srinakharinwirot University, Thailand. AB - BACKGROUND: An appropriate faculty development program is imperative for every medical school and should be tailored to suit the needs of individuals and the institution. OBJECTIVE: To measure the average level of confidence in each of the 12 roles of medical teachers and analyse if any of these factors: age, gender duration of teaching, and teaching in pre-clinical or clinical years has effect on the level of confidence in the teacher roles. MATERIAL AND METHOD: The online questionnaire invitations were sent via email to all 211 faculty members at Faculty of Medicine, Srinakharinwirot University, and 118 (55.9%) responded. The questionnaire asked about demographic data, teaching experience and their specialty or disciplines. The respondents were also asked to rate their level of confidence in each of the 12 teacher roles on a 5 point Likert scale ranging from 1 (none) to 5 (great). RESULTS: The three most highly rated roles on the level of confidence were the clinical teacher (4.11), the on the job role model (4.11) and the lecturer (3.97). The three roles with the lowest rating were the curriculum planner (3.08), the curriculum assessor (3.23) and the mentor (3.31). Age and teaching experience were positively correlated with the level of confidence in nearly all of the 12 teacher roles. The pre-clinical year teachers had a higher mean level of confidence than clinical teachers in 6 out of the 12 roles. CONCLUSION: The future faculty development programs should aim towards supporting self-evaluation of teaching, mentoring as well as promoting facilitative roles of the teacher Retention of faculty members at the institution is also important as the teaching experience significantly correlate with confidence in the teacher roles. PMID- 27276832 TI - Treatment of Disseminated Intravascular Coagulation. AB - Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic activation of blood coagulation, generation of thrombin, and leading to disturbance of the microvasculature. In this article, definition and diagnostic criteria of DIC depend on the International Society of Thrombosis and Haemostasis (ISTH). There is no gold standard for diagnosis of DIC, only low quality evidence is used in general practice. Many diagnostic tests and repeated measurement are required. For the treatment of DIC, there is no good quality evidence. The most important treatment for DIC is the specific treatment of the conditions associated DIC. Platelets and/or plasma transfusion may be also necessary if indicated. Nevertheless, there is no gold standard for diagnosis and treatment of DIC, we use only low quality evidence in general practice. PMID- 27276833 TI - Effect of Short-Term Oral Administration of Phikud Navakot in Rats. AB - BACKGROUND: Phikud Navakot (PN), composed of nine herbs and used as a main component of Yahom Navakot, is used in traditional Thai medicine against dizziness and fainting. OBJECTIVE: To investigate the effects of PN on blood pressure, heart rate (HR), and antioxidant properties on male Sprague Dawley rats. MATERIAL AND METHOD: All rats were weighted everyday in the morning, after that, PN (10, 50, 100, 200 and 400 mg/kg BW) were given oroesophageal feeding for seven days. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and HR were measured once per two days. At the end of the experiment, the blood was taken for determination of biochemical and hematological parameters, and lipid peroxidation in serum. The heart was immediately removed for Western blot analysis. RESULTS: SBP DBP and MAP of rats were transiently increased after 1 day of PN (100 mg/kg BW) treatment. Meanwhile, HR did not change throughout the experiment. PN (400 mg/kg BW) significantly increased (p< 0.05) the percentage of neutrophils in blood after 7 days of administration. PN treatment has no effect on biochemical parameters and peroxidation of lipid. In addition, ingestion of PN (100 mg/kg BW) significant increased (p < 0.05) HO-1 expression, but did not change ERK1/2 and Bax/Bcl-2 ratio when compared with the control group. CONCLUSION: The results may possibly support the use of PN for prevention and/or alleviation of cardiovascular disorders, caused by reactive oxygen species. However, long-term treatment of PN has to be further studies. PMID- 27276834 TI - Variations of the Double Eyelid and the Upper Tarsus in Asians. AB - OBJECTIVE: To identify the variations of the double eyelid shapes and the tarsal shapes in Asians and find the association between them. MATERIAL AND METHOD: Healthy subjects with natural double eyelid and age between 20-40 years were enrolled. Characteristics and variations of the eyelid shapes and the tarsal shapes were evaluated. RESULTS: Of 101 subjects, 50 were males and 51 were females. The most common shape of double eyelid fold was nasally-tapered with merging into medial upper lid fold (39.6%). Then lateral flare configuration (27.7%), parallel (26.7%), and nasally-tapered without merging into medial skin fold (5.9%), followed in descending order of frequency. Sickle type was the most common tarsal shapes observed (45.5%), then trapezoid (32.7%) and triangular type (21.8%). There was a significant association between the double eyelid shapes and the tarsal shapes. CONCLUSION: Variations of double eyelids and tarsus morphology were present among Asians. Ethnic differences should be accounted for when performing aesthetic blepharoplasty as to maintain a natural ethnic appearance. PMID- 27276835 TI - Diabetes Mellitus Treated with Medical Nutritional Therapy and Self Blood Glucose Monitoring: A Randomized Controlled Trial. AB - OBJECTIVE: To assess the effect of Medical Nutritional Therapy (MNT) combined with self blood glucose monitoring (SBGM) in the clinical outcomes of patients with type 2 diabetes. MATERIAL AND METHOD: A randomized controlled trial was conducted on patients with uncontrolled, not-using insulin type 2 diabetes at Her Royal Highness Princess Maha Chakri Sirindhorn Medical Center Sixty patients were recruited and randomized equally into intervention group (MNT with SBGM) and control group (usual care). The primary endpoint was improvement of hemoglobin A1c (HbA1c) at 12 and 24 weeks. RESULTS: At 12 and 24 weeks the intervention group had significantly improved their glycemic control in comparison to control group (median decrement of HbA1c at 12 weeks 0.72% vs. 0.15%; p < 0.001 and at 24 weeks 0.85% vs. 0.20%; p < 0.001). Oral hypoglycemic agents were reduced or discontinued in 7 patients in the intervention group and 1 patient in control group who achieved HbA1c goal after 24 weeks (p = 0.037). After 24 weeks, body weight was significantly decreased from baseline (2.3 kg, p < 0.001) in the intervention group while only non-significant decrease was observed in control group (0.1 kg, p = 0.632). CONCLUSION: MNT combined with SBGM is an effective non pharmacological intervention for patients with uncontrolled type 2 diabetes. PMID- 27276837 TI - Posterolateral Rotatory Apprehension Test in Tennis Elbow. AB - BACKGROUND: Tennis elbow is a syndrome that commonly diagnosed in patient who comes with lateral elbow pain. Instability pain in tennis elbow patient was observed and reported in many previous literatures. Posterolateral rotatory apprehension test was proposed for diagnosis of posterolateral rotatory instability of elbow. However, no review literatures that studied about posterolateral rotatory apprehensions test in tennis elbow. OBJECTIVE: To find out the relationship between posterolateral rotatory apprehension test and tennis elbow. MATERIAL AND METHOD: There were 44 patients that were recruited in this study. We examined the posterolateral rotatory apprehension test in tennis elbow patients. The examination was done in our outpatient clinic from March 2012 to April 2012. The data was collected to find out the ratio of negative test in tennis elbow patient. RESULTS: The results from the posterolateral rotatory apprehension test were negative in 43 patients. The ratio of the negative test result was 98%. CONCLUSION: A result from posterolateral rotatory apprehension test should be negative in general tennis elbow patients. If this test is used in a tennis elbow patients who are suspected with hidden instability and the result is positive, further evaluation is strongly suggested. PMID- 27276836 TI - Microvasculature Improvement of Heart in Diabetic Rat with Curcumin Supplementation. AB - OBJECTIVE: To investigate the effect of curcumin supplementation on the improvement of heart microvasculature in Streptozotocin-induced diabetic rat. MATERIAL AND METHOD: Streptozotocin (STZ: 60 mg/kg BW) was applied into rat to induce diabetic condition. Male rats were divided into three groups, control (C), diabetic (DM) and diabetic rats supplemented with curcumin (DMC) (200 mg/kg BW). After 8 and 12 weeks of experiments, heart microvasculature was investigated under vascular corrosion cast technique with scanning electron microscope (SEM). RESULTS: Destruction of heart microvasculature of DM group was observed at 8 and 12-week experiments. Five important categories of heart vessels and related veins and venules were examined respectively: right coronary arteries (RCA), medium arteries (MA), small arteries (SA), arterioles, and capillaries. RCA, cardiac arteries and veins demonstrated abnormality. Atypical patterns of vessels were presented, including shrinkage of artery vessels, capillary dropout, constriction and tortuousity of small cardiac vein and venules, and microaneurysm. At 12-week experiment, vascular lesion of DM group increased in complicated signs, including arterial constrictions and stenosis, arterial blind endings, capillary dropout and shrinkage. In addition, severity of microaneurysm dilatation of arterial branch of RCA, arterial tortuosity, coiled and twisting arteries were investigated. The diameters of vessels of all DM groups were evidently decreased. Subsequent to curcumin supplementation, typical and healthy heart microvasculatures were restored and redeveloped. The diameter sizes of DMC vessels have nearly increased back to normal situations, especially at artery, arteriole, and capillary levels. CONCLUSION: Efficiency of curcumin treatment beneficially repaired and recovered heart microvascular diabetic complications. This evidence suggests that potential anti-diabetic effect of curcumin is meaningful about the ongoing therapeutic consequences, owing to the improvement and recovery of heart blood vessels. PMID- 27276838 TI - Metabolic Syndrome in Obese Thai Children: Defined Using Modified 'The National Cholesterol Education Program/Adult Treatment Panel III' Criteria. AB - BACKGROUND: Obesity is considered to be a risk of metabolic syndrome; however, data on the prevalence of metabolic syndrome in Thai obese children are scarce. OBJECTIVE: The present study aims to determine the prevalence of metabolic syndrome in Thai obese children. MATERIAL AND METHOD: A cross-sectional study was conducted on 113 obese children who were students of a public elementary school in Ongkharak district, Thailand, in 2013. Anthropometric data, blood pressure and biochemical parameters were measured. Metabolic syndrome was defined using modified 'the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII)' criteria. RESULTS: The prevalence of metabolic syndrome in obese children was 50.4%. Children with metabolic syndrome had significantly higher waist circumference (86.9 vs. 82.4 cm, p-value = 0.049), biceps skinfold thickness (17.2 vs. 14.9 mm, p-value = 0.017), suprailiac skinfold thickness (36.5 vs. 31.8 mm, p-value = 0.019), systolic blood pressure (119.7 vs. 112.6 mmHg, p-value = 0.007), diastolic blood pressure (73.7 vs. 69.0 mmHg, p-value = 0.022), fasting blood glucose (97.4 vs. 93.6 mg/dL, p-value = 0.009) and triglyceride levels (140.0 vs. 85.6 mg/dL, p-value < 0.001) than those without metabolic syndrome. HDL-cholesterol was significantly lower in children with metabolic syndrome than those in without metabolic syndrome (48.7 vs. 63.1 mg/dL, p-value < 0.001). CONCLUSION: Of the sample, approximately half of children with obesity had metabolic syndrome. The prevalence of metabolic syndrome appears to be on the increase. Strategies for childhood obesity and metabolic syndrome prevention are urgently needed for Thai children. PMID- 27276839 TI - Demographics, Management Practices and In-Hospital Outcomes: Results from the HRH Princess Maha Chakri Sirindhorn Medical Center Acute Coronary Syndrome Registry. AB - OBJECTIVE: To determine the demographics and in-hospital outcomes of patients with acute coronary syndrome. It provides a real-life data to assess treatment strategies for acute coronary syndrome (ACS) patients. MATERIAL AND METHOD: The prospective study included patients who were hospitalized with the diagnosis of ACS during January to December, 2013. The data were analyzed in terms of characteristics, clinical presentation, treatment, and in-hospital outcomes. RESULTS: A total of 105 patients were enrolled. Mean age of all patients was 73.8 years and half of the patients were older than 70 years old. Twenty patients were classified as ST-segment elevation myocardial infarction (STEMI) and 85 as unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI). Overall prevalence of diabetes was 52.4%. The STEMI group was predominantly male, with a fewer number of diabetes than in UA/NSTEMI group. Eighty percent of the STEMI patients received reperfusion therapy. Primary percutaneous coronary intervention (PCI) was performed in 70% of STEMI patients. The median door-to needle and door-to-balloon time were 60 and 74 minutes, respectively. Six of fourteen primary PCI patients received it after 90 minutes. Nearly half of UA/NSTEMI patients went to coronary angiography and about one-third of them received revascularization with either PCI or coronary artery bypass grafting. The total mortality rate was 15% in both the STEMI patients and the UA/NSTEMI patients. CONCLUSION: This registry provided a detail of demographics, management practices, and in hospital outcomes of ACS patients. Door-to-needle time and door to-balloon time were considered as suboptimal. In-hospital mortality was higher than the latest national average. Patient delay should be improved by giving more education to the general public and concerted effort to improve in-hospital time delay is warranted. These data have an impact on our patient care system and alert our team to improve patient care. PMID- 27276840 TI - Neurovascular Complications in Forty-Nine Cases Elbow Arthroscopy and Review Literatures. AB - BACKGROUND: An elbow arthroscopic surgery is a minimally invasive surgery. There were several international publications report neurovascular complications in elbow arthroscopic surgery. But there was no study which was conducted in Thailand OBJECTIVE: To report the result of elbow arthroscopic surgery which focus on the neurovascular complications. MATERIAL AND METHOD: A retrospective review of elbow arthroscopic surgery between April 2011 to May 2014 at HRH Princess Maha Chakri Sirindhorn Medical Center Srinakharinwirot University in Nakhon Nayok province was performed. The data of complications were collected since immediately after surgery until 6 weeks after procedure. RESULTS: Forty nine elbow arthroscopic surgeries were performed in 44 patients. The authors found total complications occurred in 2 cases (4%) which were minor complications. One case was transient cutaneous nerve injury (2%) and another case was cellulitis around a portal site (2%). No serious or permanent complication was detected. CONCLUSION: Elbow arthroscopic surgery is considered a safe operation, because only one minor neurological complication was observed and no major neurovascular complications were detected. PMID- 27276841 TI - The Pilot Study of the Effect of Meditation to the Serum Brain-Derived Neurotrophic Factor (BDNF) of Medical Students, Srinakharinvirot University. AB - BACKGROUND: Mindfulness meditation is a method to decrease stress and increase memory. So, mindfulness meditation should increase serum brain-derived neurotrophic factor (BDNF). OBJECTIVE: To study the effect of mindfulness meditation on the serum BDNF of medical students. MATERIAL AND METHOD: The study group consisted of 30 male and female second-year medical students that volunteered to participate in the study, aged 19.1 +/- 0.55 year olds (range 18 20) from Srinakharinwirot University. Their blood was drawn to measure BDNF before and after a four-day mindfulness meditation programme. The comparison of serum BDNF levels before and after meditation were analysed by paired t-test. RESULTS: The subjects were 66.77%female and 33.33% male. The average serum BDNF level before the meditation was 17.67 ng/ml (SD 3.58). After meditation, there was a decrease in serum BDNF to 17.34 ng/ml, which was however not statistically significant (SD 4.04, p > 0.05). CONCLUSION: The levels of blood BDNF decreases slightly after practising meditation. We plan to investigate the reason in the future. PMID- 27276842 TI - The Effects of Single-Dose Preoperative Intravenous Dexamethasone on Clinical Outcome after Laparoscopic Cholecystectomy. AB - BACKGROUND: Laparoscopic cholecystectomy is one of the most common procedures in surgery. Post-operative pain and post- operative nausea and vomiting (PON) are frequently events after laparoscopic cholecystectomy and cause distress to patients. Dexamethasones are known for analgesic, anti-inflammatory, immune modulating and anti-emetic effects. Therefore, preoperative dexamethasone administration may reduce postoperative pain and postoperative nausea vomiting after laparoscopic cholecystectomy. OBJECTIVE: This study aims to determine the effects of single-dose preoperative intravenous dexamethasone on clinical outcome such as postoperative pain nausea and vomiting in patients undergoing laparoscopic cholecystectomy. MATERIAL AND METHOD: This is a prospective randomized controlled trial study. Eighty patients undergoing elective laparoscopic cholecystectomy were randomized to dexamethasone group and control group. Dexamethasone group received 8 mg (2 ml) of intravenous dexamethasone 60 90 minute before surgery whereas control group received 2 ml of normal saline 60 90 minute before surgery. Patients received a similar standardized anesthesia, surgical and multimodal analgesic treatment. The pain score, nausea and vomiting at 1, 6, 24 hours after surgery and before discharge including analgesic consumption and antiemetic required was recorded in both groups. Preoperative and postoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. RESULTS: No significant difference existed between two groups regarding age, sex, previous operation, operation time and hospital stays. All of the patients had no postoperative complication. Postoperative pain score, nausea and vomiting at 1st and 6th hours in dexamethasone group were significantly reduced in comparison with control group. Analgesic consumption, antiemetic requirement and CRIP postoperative were significantly decreased in dexamethasone group. CONCLUSION: Single-dose preoperative dexamethasone 8 mg 60-90 minute before induction of anesthesia improved clinical outcome in terms of significantly less nausea, vomiting, pain at first 6 hours and less inflammatory response after laparoscopic cholecystectomy compared to placebo. The preoperative dexamethasone should be used as routine in patients undergoing laparoscopic cholecystectomy. PMID- 27276843 TI - Xanthones Isolated from the Pericarp of Mangosteen Inhibit Neurotransmitter Receptors Expressed in Xenopus Oocytes. AB - OBJECTIVE: This study aimed to evaluate inhibitory effects of 7 xanthones and 3 extracts obtained from the pericarp of mangosteen on serotonin (5-HT), N-methyl-D aspartate (NMDA) and glycine receptors expressed in Xenopus oocytes. MATERIAL AND METHOD: Xenopus oocytes were injected with RNA of either 5-HT NMDA or glycine receptor and inhibitory effects of the xanthones and extracts were investigated using the two-electrode voltage clamp technique. RESULTS: Xanthones from the pericarp of mangosteen affected 5-HT NMDA and glycine receptor functions with different degree of inhibition. Alpha-mangostin, garcinone-D and 9-hydroxycalaba xanthone inhibited 5-H T-induced currents by more than 80%. Gamma-mangostin and garcinone-E did by more than 50%, but not more than 80%. Garcinone-C and garcinone- D inhibited glutamate-induced currents by more than 80%. The alcohol extract did by more than 50%, but not more than 80%. Alpha-mangostin, garcinone C, garcinone-D, non-tannin extract and the alcohol extract inhibited glycine induced currents between 50-70%, neither compounds inhibited the currents up to 80%. CONCLUSION: These results suggest that each xanthone derivatives has different selectivity to different types of neurotransmitter receptors. PMID- 27276844 TI - Lack of Association between IL-10 Gene Promoter Polymorphisms and Susceptible to Tuberculosis in Thai Patients. AB - BACKGROUND: Cytokines play a major role in defense against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Polymorphisms of the regulatoy cytokine gene, the interleukin (IL)-10 is associated with the risk of tuberculosis (TB) in different populations. However IL-10 gene polymorphism and susceptibility to TB in Thai is still unknown. OBJECTIVE: The purpose of this study was to evaluate whether the common IL-10 promoter gene polymorphisms are associated with TB in Thai population. MATERIAL AND METHOD: Forty-eight patients with newly diagnosed pulmonary tuberculosis were studied. DNA samples were extracted from leukocytes and used to investigate -1087A/G -819C/T -252C/A (rs1800896, rs1800871, rs1800872) in IL-10 gene using restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: In this study, the genotype and allele frequencies of IL-10-1087A/G, -819C/T -252C/A polymorphism did not significantly different between TB patients and healthy controls ((genotype: p = 0.38, p = 0.92,p = 1; allele: p = 0.57, p = 0.77, p = 0.89, respectively). CONCLUSION: The lack of association between common IL-10 promoter polymorphisms and TB susceptibility in this study may provide clue for better understanding of IL-10 1087A/G -819C/T -252C/A polymorphism and TB susceptibility in Thai population, which might facilitate the rationale design of vaccines. However further studies in large scales population are required for confirmation. PMID- 27276845 TI - Functional Results in Arthroscopic Treatment in Patients with Chronic Lateral Elbow Pain. AB - BACKGROUND: Modern surgery as elbow arthroscopic surgery is an accepted operation due to benefit in precise intra-articular lesion detection and minimally invasive surgery. OBJECTIVE: To report the functional results when using arthroscopic surgery to treat chronic lateral elbow pain. MATERIAL AND METHOD: The data was collected from 25 patients with chronic lateral elbow pain that failed in non operative treatment and treated with elbow arthroscopic surgery. Five patients were excluded from this study due to diagnosed as instability that needed the ligament reconstruction. The etiology of pain were grouped in to tennis elbow (4 pts), plica (9 pts), tennis elbow combined with plica (4 pts) and cartilage lesion (3 pts). Thai quick DASH questionnaire was used to evaluate the functional results by comparing pre and post operation score and calculated statistic results with paired t-test by level of significance p < 0.05. RESULTS: The mean follow-up after surgery was 22 months by mean disability module pre and post operative score is 68 and 18 respectively. In the occupation module was 74 and 25 respectively and in sports module was 81 and 17 respectively. All modules, scores was significant improved with p-value = 0.000, 0.000 and 0.004 respectively. The disability mean score in pre and post-operative along the diagnosis, tennis elbow mean score was 74 and 33, in plica lesion mean score was 65 and 11, combined lesions mean score was 60 and 18 and cartilage lesion mean score was 60 and 20. CONCLUSION: Approaching chronic lateral elbow pain with arthroscopy can maintain the signficant improvement of functional result in midterm follow-up. PMID- 27276846 TI - Glycated Haemoglobin and Diabetic Retinopathy in Type 2 Diabetic Patients in HRH Princess Maha Chakri Sirindhorn Medical Center. AB - OBJECTIVE: Diabetic retinopathy (DR) is an important cause of blindness in type 2 diabetic patients. When it occurs, it affects the patient's quality of life including their physical activity, emotion, mentality, and social interactions. Therefore, the objectives of this research were to study the relationship between glycaemic control and DR and the relationship between DR and other factors. We also aim to find the optimal cut-off point to screen diabetic retinopathy using glycated haemoglobin (HbA1c) levels. MATERIAL AND METHOD: We performed a case control study. One hundred patients were divided into two groups (50 patients for DR group and 50 patients for non-DR group). Their HbA1c, weight, height, blood pressure, and lipid profiles were retrospectively reviewed by Electronic Medical Record (EMR). The data was analysed using both Chi-square test and logistic regression with two-tailed hypothesis. RESULTS: The research revealed that uncontrolled glycaemic in type 2 diabetic patients was significantly related to DR (Adjusted odds ratio 8.89, 95% CI = 2.3-18.00, p-value < 0.001). In addition, it occurred more commonly in males (Adjusted odds ratio 6.41, 95% CI = 3.02 26.25, p-value < 0.001). A cut-off level of HbA1c for screening DR is 7.25% (sensitivity 84%, specificity 66%, positive predictive value = 71.2%, negative predictive value = 80.5%). CONCLUSION: HbA1c level and male gender are strongly related to DR (p < 0.001) and the optimal cut-off level for DR screening is 7.25% in type 2 diabetic patients that were treated in HRH Princess Maha Chakri Sirindhorn Medical Center. PMID- 27276847 TI - Early Onset Neonatal Sepsis Due to Salmonella enterica Serovar 4,5,12:i:-: A Case Report with Literature Review. AB - The authors report a case of a 36-week male infant born via spontaneous vaginal delivery who developed Salmonella sepsis at HRH Princess Maha Chakri Sirindhorn Medical Center Srinakharinwirot University, Nakhon Nayok, Thailand. He was born to a mother without identifiable risk factors. On day 3, he developed fever tachycardia, lethargy, poor feeding and diarrhea prompting a sepsis evaluation. Blood and stool cultures were positive for S. enterica serovar 4,5,12:i:-. Therefore, Salmonella infection should be considered in the differential diagnosis of early onset neonatal sepsis (EOS) particularly in endemic areas. PMID- 27276848 TI - Unusual Skin Manifestations in Neonatal Lupus Erythematosus. AB - Neonatal lupus erythematous (NLE) is a rare autoimmune disease caused by placental transfer of maternal anti-SSA/Ro or anti-SSB/La antibodies. It usually presents with transient cutaneous lesions, congenital heart block and other systemic symptoms. The authors report a case of neonatal lupus erythematosus who presented with targetoid-like lesions on both feet. PMID- 27276849 TI - A Report of Peritonitis from Aeromonas sobria in a Peritoneal Dialysis (PD) Patient with Necrotizing Fasciitis. AB - A 70-years of age, male patient with underlying type 2 diabetes mellitus, hypertension, dyslipidemia and ischemic heart disease had undergone continuous ambulatory peritoneal dialysis (CAPD)for 3 years without any episodes of peritonitis. He was diagnosed with necrotizing fasciitis and later developed peritonitis after receiving a laceration from an aquatic injury suffered during the flood disaster of 2011. The blood culture, necrotic tissue and the clear dialysate collected upon admission had shown Aeromonas sobria. The route of peritonitis may be from the hematogenous spread of A. sobria resulting in necrotizing fasciitis. A. sobria should be considered as the pathogen of peritonitis in PD patients who have history of wounds from contaminated water. We suggest that the PD patients who present with septicemia and did not meet the criteria for peritonitis, the initial dialysate effluent should be sent for culture. The benefit of this is to allow early recognition and treatment of peritonitis. PMID- 27276850 TI - Laparoscopic Radical Cystoprostatectomy, Surgical Technique and Result: A Case Report. AB - OBJECTIVE: Laparoscopic radical cystoprostatectomy is a complicated operation. The objective of this study is to present our technique and results of laparoscopic radical cystoprostatectomy. MATERIAL AND METHOD: A 72-year-old Thai male presented with gross hematuria. Cystoscope was performed. Large bladder tumor near right ureteric orifice was observed. Then, transurethral resection of bladder tumor was performed. His tumor pathology was muscle invasive high grade urothelial carcinoma with clinical staging T2N0M0. Laparoscopic radical cystoprostatectomy was then conducted with bilateral pelvic nodes dissection and ileal conduit. RESULTS: Operation period was eight hours. Blood loss was 500 ml. In pathological results, tumor invaded bladder muscle into perivesical tissue. Tumor margin was free. Lymph nodes were positive for malignancy 5/7 for right side and 0/4 for left side. Pathological staging was T3aN1M0. After post operative period, the patient was discharged from hospital uneventfully. CONCLUSION: Laparoscopic radical cystoprostatectomy in Maha Chakri Sirindhorn Medical Center is minimal invasive, feasible and safe. However, a longer follow up period regarding long-term cancer control as well as functional and technical aspects will be required. PMID- 27276851 TI - Carotid artery wall stiffness is increased in patients with small vessel disease: A case-control study. AB - INTRODUCTION: Cerebral ischemic small-vessel disease (SVD), causing lacunar infarcts and white matter hyperintensities on brain magnetic resonance imaging (MRI), is a progressive disease associated with an increased risk of stroke, dementia and death. Increased arterial stiffness has been associated with ischemic stroke and cerebral SVD independently of common vascular risk factors. OBJECTIVE: The aim of the study was to analyze arterial stiffness in our patients with symptomatic SVD. METHODS: In a cross-sectional study design we included 30 patients with clinical and MRI evidence of cerebral SVD and 30 age-, gender- and risk factor-matched control subjects with no neurological diseases. Patients were evaluated at the Ultrasound Laboratory at the Neurology Clinic, Clinical Center of Serbia in Belgrade, during a three-month period (from September 1st to December 1st 2012). Baseline demographic and vascular risk factors were recorded. All patients underwent standard carotid ultrasound scans with measuring of intima media thickness (IMT) and analysis of atheromatous plaques. Internal carotid artery stiffness was evaluated with the use of e-tracking option as beta stiffness index (BSI) value. RESULTS: There were no differences between study groups in regard to degree of carotid stenosis and type of carotid plaques (p > 0.05). Patients in SVD group had significantly higher mean IMT (p = 0.0093) and mean BSI (p < 0.0001) than subjects in the control group. No significant correlation was detected between IMT and BSI in SVD group (r = 0.168; p = 0.376). Brain lesions severity correlated with BSI (r = 0.733; p < 0.0001). CONCLUSION: Arterial stiffness is increased in symptomatic patients with SVD, independently of vascular risk factors and IMT. PMID- 27276852 TI - Estimation of total bacteria by real-time PCR in patients with periodontal disease. AB - INTRODUCTION: Periodontal diseases are associated with the presence of elevated levels of bacteria within the gingival crevice. OBJECTIVE: The aim of this study was to evaluate a total amount of bacteria in subgingival plaque samples in patients with a periodontal disease. METHODS: A quantitative evaluation of total bacteria amount using quantitative real-time polymerase chain reaction (qRT-PCR) was performed on 20 samples of patients with ulceronecrotic periodontitis and on 10 samples of healthy subjects. The estimation of total bacterial amount was based on gene copy number for 16S rRNA that was determined by comparing to Ct values/gene copy number of the standard curve. RESULTS: A statistically significant difference between average gene copy number of total bacteria in periodontal patients (2.55 x 107) and healthy control (2.37 x 106) was found (p = 0.01). Also, a trend of higher numbers of the gene copy in deeper periodontal lesions (> 7 mm) was confirmed by a positive value of coefficient of correlation (r = 0.073). CONCLUSION: The quantitative estimation of total bacteria based on gene copy number could be an important additional tool in diagnosing periodontitis. PMID- 27276853 TI - Relationship between the vertical craniofacial disproportions and the cervicovertebral morphology in adult subjects. AB - INTRODUCTION: Orthodontic diagnosis includes the interpretation of the relations between the craniofacial and cervical system, given the potential impact of the irregularities from one system to another. OBJECTIVE: The aim of this study was to examine morphological characteristics of the cervical spine, depending on the parameters of the vertical craniofacial growth and gender in adult subjects. METHODS: The sample comprised lateral cephalograms of 120 subjects with different vertical facial growth, aged 17.5-35 years. Measured parameters were the following: anterior and posterior vertebral body height (ABHC2-C5, PBHC2-C5), anterior and posterior intervertebral space (AISC2-C5, PISC2-C5), distance between vertebrae and point sella (SC2, SC3, SC4), pterygomaxillare (PmC2), gonion (GoC2) and basion (BaC4); cervical spine angulation (OPT/CVT) and inclination (OPT/HOR, CVT/HOR). RESULTS: Results showed that subjects with anterior facial growth rotation have greater values for BaC4, OPT/HOR, CVT/HOR, OPT/CVT, anterior and posterior vertebral body heights and intervertebral spaces, and lower values for GoC2 and PmC2. Higher values in males were found for anterior and posterior vertebral body heights, distances SC2, SC3, SC4, and BaC4. In females, the greater values were found for GoC2 and OPT/CVT. CONCLUSION: Subjects with anterior facial growth rotation have greater cervical spine inclination and angulation, higher cervical vertebrae and intervertebral spaces, longer upper cervical spines and shorter distances GoC2 and PmC2. Males show smaller cervical column curvature, but higher cervical vertebrae and greater length of the upper cervical spine. PMID- 27276854 TI - Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. AB - INTRODUCTION: Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. OBJECTIVE: We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. METHODS: A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients'status was assessed by an office visit or telephone interview. RESULTS: Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n = 217). Groups had similar total ischemic time (319 +/- 276 vs. 333 +/- 372 min; p = 0.665), but TA+ group had higher maximum values of troponin I (39.5 +/- 30.5 vs. 27.6 +/- 26.9 ng/ml; p < 0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e' > 15, as a marker of severe diastolic dysfunction' (TA+ 23.1% vs. TA- 15.2%; p = 0.050). During average follow-up of 14 +/- 5 months, major adverse cardiac/cerebral events occurred at the similar rate (log rank p = 0.867). CONCLUSION: Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn't influence the incidence of major adverse cardiovascular events. PMID- 27276855 TI - Correlation between demographic characteristics, cognitive functioning and functional independence in stroke patients. AB - INTRODUCTION: It has been assumed that there is causality of the achieved level of functional independence with the degree of preservation of cognitive function in stroke patients. Demographic characteristics may be important for monitoring the achieved level of functional independence. OBJECTIVE: The aim of this study was to examine the relationship of demographic characteristics and functional independence in regard to the level of cognitive impairment in stroke patients. METHODS: The study included 50 stroke patients after rehabilitation, as well as age- and gender-matched 50 subjects selected randomly, according to the demographic characteristics of the studied sample, who in their medical history had no neurological disorders. For the assessment of functional independence, the Functional Independence Measure (FIM) test was used.The general cognition was estimated by the Mini-Mental State Examination (MMSE) test. The statistical analyses included the Mann-Whitney test, for two independent samples, measures of canonical correlation, and chi2 test. RESULTS: There was a statistically significant difference between the groups in relation to risk factors, hypertension and diabetes mellitus type II (p < 0.001); There was a statistically significant difference within the groups in relation to the cognitive impairment in all the examined demographic characteristics (p<0.001); the differences within the groups in relation to the cognitive impairment are present on all subscales of the FIM test (p < 0.05); the differences within the groups in relation to handedness, hemiparesis, show that mild cognitive impairment is more common among left hemiparesis, while a more severe one is more common among right-sided hemiparesis (p < 0.05); More severe cognitive impairment is common among women, the elderly and in persons with lower education (p < 0.05). CONCLUSION: By prevention of risk factors, and prevention of possible cognitive impairment, consequences of stroke can be reduced, the recovery can be made more successful, and quality of life can be improved. PMID- 27276856 TI - Clinical trial/experimental study (consort compliant): Optimal time period to achieve the effects on synbiotic-controlled wheezing and respiratory infections in young children. AB - INTRODUCTION: Urban life is often followed by immune dysfunction and loss of immune tolerance in the youngest children. OBJECTIVE: The study aimed to determine optimal time efficiency of a synbiotic (5 x 109 Lactobacillus acidophilus Rosell-52, Bifidobacterium infantis Rosell-33, Bifidobacterium bifidum Rosell-71) in controlling respiratory infections and wheezing disease. METHODS: We randomly selected a group of children younger than five years, hospitalized earlier, and classified them into three groups. RESULTS: The incidence of respiratory infection before the study was once a month, while after a three-month supplementation with the synbiotic children rarely suffered from respiratory infections, and the state was maintained after six-month and nine month supplementations with the synbiotic. The decreased incidence of respiratory infections was followed by a falling incidence of concomitant wheezing. A significant increase in tIgA serum was observed in all groups for only three months, the increase being the highest in children with recurrent respiratory infections accompanied by wheezing. After a nine-month administration of the synbiotic, total IgE serum was lower in all groups of patients. CONCLUSION: The optimal duration of administration of the synbiotic containing three probiotic cultures to provide effective control of the frequency of respiratory infections was three months, and six months were required to establish control of the frequency of wheezing. This synbiotic is useful for immunomodulation in children and is well-tolerated in young children. PMID- 27276857 TI - Displaced supracondylar humeral fractures in children: Comparison of three treatment approaches. AB - INTRODUCTION: Closed reduction and percutaneous pinning are the most widely used treatment options for displaced supracondylar humerus fractures in children, but there is still no consensus concerning the most preferred technique in injuries of the extension type. OBJECTIVE: The aim of this study was to compare three common orthopaedic procedures in the treatment of displaced extension type supracondylar humerus fractures in children. METHODS: Total of 93 consecutive patients (66 boys and 27 girls) referred to our hospital with Gartland type II or III extension supracondylar humeral fractures were prospectively included in the study over a six-year period. At initial presentation 48 patients were classified as Gartland type II and 45 as Gartland type III fractures. The patients were subdivided into three groups based on the following treatment modality: closed reduction with percutaneous pinning, open reduction with Kirschner wires (K wires) fixation, and closed reduction with cast immobilisation. The treatment outcome and clinical characteristics were compared among groups, as well as evaluated using Flynn's criteria. RESULTS: Excellent clinical outcome was reported in 70.3% of patients treated with closed reduction with percutaneous pinning and in 64.7% of patients treated with open reduction with K-wire fixation. The outcome was significantly worse in children treated with closed reduction and cast immobilisation alone, as excellent outcome is achieved in just 36.4% of cases (p = 0.011). CONCLUSION: Closed reduction with percutaneous pinning is the method of choice in the treatment of displaced pediatric supracondylar humeral fracture, while open reduction with K-wire fixation is as a good alternative in cases with clear indications. PMID- 27276858 TI - Fungal infections in corn picker hand injury. AB - INTRODUCTION: Hand injuries caused by corn pickers are relatively rare but in most cases extensive, with massive tissue destruction. Severe wounds sustained during agricultural work are contaminated, with high incidence of infection. OBJECTIVE: The aim of the study was to determine the frequency and type of fungal infection in corn picker injuries and their impact on the course and outcome of treatment. METHODS: Corn picker hand injuries for the period 2006-2012 were analyzed. After setting up clinical suspicion, direct examination of repeated swabs and histopathological analysis of biopsy material were done in order to detect fungi. RESULTS: From the total number of 60 patients, there was a fungal infection in nine of them (which makes 15% of the total number of patients). Aspergillus spp. was isolated in seven patients, Candida spp. in three, and Mucor spp. in one patient. None of the patients had increased risk factors for developing a fungal infection. In most cases, there was loss of graft and tissue necrosis in previously normally look- ing wound, after seven or more days. All patients were treated with repeated surgical debridement and concomitant parenteral and topical application of appropriate antifungal agents. There was no need for reamputation in any patient. CONCLUSION: A high degree of suspicion and a multidisciplinary approach are needed for early diagnosis of fungal infection. Confirmation of diagnosis and the initiation of surgical and appropriate antifungal therapy are essential for a successful outcome. PMID- 27276859 TI - Clinical and laboratory differences between Epstein-Barr and cytomegalovirus infectious mononucleosis in children. AB - INTRODUCTION: Infective mononucleosis is most commonly caused by Epstein-Barr virus (EBV), and in smaller percentage by cytomegalovirus (CMV). OBJECTIVE: The aim of this paper was to determine the clinical and laboratory differences between EBV and CMV infectious mononucleosis in children. METHODS: Cohort retrospective analytical research was conducted. We used data from medical history in six years period and monitored anamnestic data, frequency of inspection and palpation obtained data during physical examination, several laboratory tests, abdomen ultrasonography examination finding and emergence of disease complications. Statistical processing of data has been performed using SPSS 20. RESULTS: Total number of examined children was 137, out of which 85.4% were with EBV and 14.6% with CMV infection. Affected children were most commonly younger than eight years. Boys were affected more often. There was no difference in frequency of high temperature, sore throat, bad breath, and respiratory symptomatology between examined children. Differences were discovered in frequency of stomachaches, eyelid swelling, skin rash and fatigue. Differences were not proven in the frequency of angina, lymphadenopathy and splenohepatomegaly between the groups. Values of transaminases and lactic dehydrogenases significantly decreased after seven days of hospitalization in both groups. In children with EBV, values of transaminases declined faster than in children with CMV. Anemia and bacterial superinfection of pharynx were most common disease complications. Thrombocytopenia was more common in children with CMV infection. Average duration of hospitalization was 6.7 days. CONCLUSION: In children with CMV abdominal pain, eyelid swelling, skin rash, fatigue and thrombocytopenia were more common. In children with EBV values of transaminases declined significantly faster. PMID- 27276861 TI - Doppler changes as the earliest parameter in fetal surveillance to detect fetal compromise in intrauterine growth-restricted fetuses. AB - INTRODUCTION: It is estimated that 3-10% of infants are growth restricted. Growth disturbances may have long-term issues. Doppler allows insight into the fetal response to intrauterine stress. OBJECTIVE: The aim of this study was to detect fetal compromise in intrauterine growth-restricted (IUGR) fetuses by means of biophysical profile (BPP) vis-a-vis Doppler velocimetry studies of the fetal umbilical artery, and to find out which of the two is a better and earlier predictor of fetal compromise. METHODS: A prospective study was conducted on a total of 50 singleton pregnancies with IUGR between 28 and 42 weeks of gestation. Study patients were managed expectantly with nonstress testing and amniotic fluid assessment, BPP and Doppler velocimetry studies of the fetal umbilical artery. RESULTS: Fetal outcome was poor in 5/50 (10%) of the fetuses, defined as presence of all of the following: poor Apgar test score, neonatal intensive care unit stay, necrotizing enterocolitis, and low birth weight. Of the four with abnormal BPP, 50% had poor fetal outcomes. Out of 46 with normal BPP, 6.5% had poor fetal outcomes. CONCLUSION: Inference drawn from the study is that the Doppler technology provides us the opportunity for repetitive noninvasive hemodynamic monitoring in IUGR pregnancies. PMID- 27276860 TI - Epidemiological characteristics and clinical manifestations of hepatitis E virus infection in Bulgaria: A report on 20 patients. AB - INTRODUCTION: Hepatitis E is one of the leading clinical manifestations of acute viral hepatitis in developing countries. In industrialized countries, during the past several years, sporadic "autochthonous" cases of HEV infection have been increased. OBJECTIVE: The aim of this study was to analyze the epidemiological, clinical and laboratory features of HEV infection among patients hospitalized at the Department of Infectious Diseases in Military Medical Academy, Sofia, Bulgaria. METHODS: A retrospective study of 806 cases of acute viral hepatitis was performed at the Department of Infectious Diseases in Military Medical Academy, Sofia, Bulgaria, between December 2004 and September 2012.The etiological diagnosis was established by ELISA. The statistical analysis was performed using Excel 2007 (Microsoft, Redmond, Washington, USA) and SPSS Statistics 19.0 (IBM Corp., Armonk, NewYork, USA). RESULTS: Specific reaction to anti-HEV-IgM and anti-HEV-IgG antibodies were detected in 20 (2.48%) of 806 patients. The most observed clinical presentations were jaundice (85%), fatigue (85%), anorexia (65%), abdominal discomfort (55%) and fever (40%). The mean values of aspartate transaminase and alanine transaminase were 521 IU/l and 881 IU/l, respectively. The cholestasis was slight, marked with mean values of gamma glutamyl transferase and alkaline phosphatase, respectively 418 IU/I and 486 IU/I. CONCLUSION: We report twenty autochthonous sporadic cases of acute infection with HEV. The zoonotic etiology of the virus as well as the foodborne transmission of the infection is discussed. We found that aging and pre-existing underlying diseases are risk factors for a severe course of the HEV infection. PMID- 27276862 TI - Iris melanocytoma. AB - INTRODUCTION: Iris melanocytoma (IM) is a rare benign tumor, but unavoidable in differential diagnosis of pigmented iris lesions. According to the best knowledge of the authors it is for the first time in Serbia that a well-documented case of IM is presented and that the problem of this tumor is discussed. CASE OUTLINE: In the left eye of a 47-year-old white female at the iris in a six o'clock position, a highly pigmented, dome shaped lesion with a crater-like cavity in the center and with feathery margins was noticed. There were no signs of infiltration of surrounding tissue or intrinsic vessels and the lens was clear. Visual acuity and intraocular pressure were normal. An ultrasound biomicroscopy (UBM) revealed a well-defined lesion with high internal reflectivity, with a base diameter of 1.25 mm and a thickness of 0.80 mm in the periphery, and 0.53 mm in the central part.The diagnosis of IM of the left eye was established and regular checkups were performed for ten years. No changes in clinical or UBM presentation were established. CONCLUSION: Awareness of clinical presentation of IM is most important for correct diagnosis. Ultrasound biomicroscopy is a useful diagnostic procedure in the following up of IM. PMID- 27276863 TI - Peripartum cardiomyopathy in a patient treated for acute myeloid leukemia. AB - INTRODUCTION: Peripartum cardiomyopathy usually presents with systolic heart failure during the last months of pregnancy and up to five months postpartum. The disease is rare and can be fatal. CASE OUTLINE: We report a 30-year-old female who was diagnosed with acute myeloid leukemia, with maturation and cytogenetic finding of t(8;21)(q22;q22),del(9)(q22) in January 2004. She was treated with chemotherapy and achieved complete remission that lasts to date. She became pregnant and delivered a healthy newborn with caesarean section in 2009. Seven months later, she again became pregnant and delivered the second child with caesarean section in January 2011. Seven days after delivery she developed symptoms and signs of heart failure. Electrocardiogram showed sinus rhythm, low voltage and negative T-waves in inferior and lateral leads. Echocardiography revealed global left ventricular dysfunction with ejection fraction of 15%, with mobile thrombotic mass of 12 mm attached to the left ventricle wall. She was treated with both unfractionated and low-molecular heparin, diuretics, cardiotonics, and beta-blockers. Within six following weeks left ventricle systolic function improved up to 25-30%. The full clinical recovery was achieved in September 2013, resulting in absence of heart failure and left ventricular ejection fraction of 54%. CONCLUSION: Peripartum cardiomyopathy is a rare condition. The cause of cardiomyopathy is unknown, but it is believed that it could be triggered by various conditions and risk factors. Although the patient was treated with cardiotoxic drugs (doxorubicin and mitoxantrone) in permitted doses, they could have been contributory factors of myocardial damage. Close monitoring of cardiac function in the peripartal period might be beneficial in patients treated with cardiotoxic drugs. PMID- 27276864 TI - A case of essential thrombocythemia and ankylosing spondylitis treated with a combination of anagrelide, disease-modifying antirheumatic drugs, and etanercept. AB - INTRODUCTION: A high platelet count, or thrombocytosis, is either a reactive process or a result of a myeloproliferative disorder. Ankylosing spondylitis is a chronic inflammatory rheumatic disease affecting the spine and sometimes peripheral joints in which reactive mild to moderate thrombocytosis is a common finding. There have been no previously reported cases of essential thrombocythemia associated with ankylosing spondylitis. CASE OUTLINE: We report a case of a 32-year-old man with human leukocyte antigen B27-positive ankylosing spondylitis and Janus kinase 2-positive essential thrombocythemia who was treated first with a combination of anagrelide and disease-modifying antirheumatic drugs and, after liver toxicity, with a combination of anagrelide and etanercept (TNF alpha antagonist). Both diseases were gradually brought under control. CONCLUSION: Our case of ankylosing spondylitis and essential thrombocythemia suggests that concomitant etanercept and anagrelide therapy is safe, as well as effective. PMID- 27276865 TI - "Stray" achalasia: From gastroenterologist to pulmonologist and back. AB - INTRODUCTION: Achalasia is a rare esophageal disorder which, due to frequent presence of both respiratory and gastrointestinal symptoms, can initially be referred either to pulmonologist or gastroenterologist. CASE OUTLINE: A 50-year old patient was initially referred to gastroenterologist with the following symptoms: nausea, vomiting, occasional hiccups, weight loss, chest pain, dysphonia, and dry cough. After chest X-ray, the patient was referred to pulmonologist with differential diagnosis for pulmonary infiltration and thoracic aortic aneurysm. Pulmonologist interpreted chest X-ray as showing paratracheal mediastinal enlargement with air-fluid levels, thus suspecting achalasia. Computed tomography scan of the thorax with per os contrast showed extremely dilated esophagus with food stasis. The patient was then referred to thoracic surgeon, who ordered additional diagnostics (esophageal passage with contrast, esophagomanometry, esophagogastroduodenoscopy), and finally performed Heller myotomy. Postoperatively there were no complications, and the patient was symptom free during the follow-up. CONCLUSION: Although achalasia can also result in respiratory symptoms, fastidious anamnesis and accurate radiological interpretation are essential for the correct diagnosis. PMID- 27276866 TI - Case report of an infant with severe vitamin D deficiency rickets manifested as hypocalcemic seizures. AB - INTRODUCTION: Hypocalcemic seizures are uncommon in the post-neonatal period. We report an infant with hypocalcemic seizures caused by severe deficiency of vitamin D. CASE OUTLINE: A five-month-old male infant was admitted to hospital in March 2013 with recurrent generalized afebrile seizures resistant to clonazepam therapy. At the clinical examination, the infant showed characteristic rachitic signs, so that after a blood sample was taken for laboratory testing, the infant was given infusion of 2 ml/kg of 10% of calcium gluconate at a rate of 0.5 ml/min.The treatment resulted in immediate termination of seizures and normalization of the consciousness of the infant. Blood sample analysis showed extremely low levels of free and total calcium (0.36/1.24 mmol/) and 25(OH)D (<3 ng/ml), elevated alkaline phosphatase (878 U/) and parathyroid hormone (283 pg/ml), and low calcium/creatinine ratio (mg/mg) in a portion of urine (0.03), while the levels of serum phosphorus, pH, total protein, albumin and creatinine were within the reference range. Wrist X-ray showed typical signs of rickets. In order to fully stabilize calcium homeostasis, along with 2,000 IU of vitamin D3 daily and standard cow's milk formula, calcium gluconate (80 mg/kg daily) was given orally over a period of two weeks.The treatment resulted in complete stabilization of the infant's condition and rapid improvement in laboratory, radiological and clinical findings of rickets. CONCLUSION: Generalized convulsions in the afebrile infant represent a serious and etiopathogenically very heterogeneous problem. Extremely rare, as in the case of our patient, it may be due to severe hypocalcemia caused by a deficiency of vitamin D. PMID- 27276867 TI - Recent advances in research on non-auditory effects of community noise. AB - Non-auditory effects of noise on humans have been intensively studied in the last four decades. The International Commission on Biological Effects of Noise has been following scientific advances in this field by organizing international congresses from the first one in 1968 in Washington, DC, to the 11th congress in Nara, Japan, in 2014. There is already a large scientific body of evidence on the effects of noise on annoyance, communication, performance and behavior, mental health, sleep, and cardiovascular functions including relationship with hypertension and ischemic heart disease. In the last five years new issues in this field have been tackled. Large epidemiological studies on community noise have reported its relationship with breast cancer, stroke, type 2 diabetes, and obesity. It seems that noise-induced sleep disturbance may be one of the mediating factors in these effects. Given a large public health importance of the above-mentioned diseases, future studies should more thoroughly address the mechanisms underlying the reported association with community noise exposure. Keywords: noise; cancer; stroke; diabetes mellitus type 2; obesity PMID- 27276868 TI - Food allergy in children. AB - Food allergy represents a highly up-to-date and continually increasing problem of modern man. Although being present in all ages, it most often occures in children aged up to three years. Sensitization most often occurs by a direct way, but it is also possible to be caused by mother's milk, and even transplacentally. Predisposition of inadequate immune response to antigen stimulation, reaginic or nonreaginic, is of non-selective character so that food allergy is often multiple and to a high rate associated with inhalation and/or contact hypersensitivity. Also, due to antigen closeness of some kinds of food, cross-reactive allergic reaction is also frequent, as is the case with peanuts, legumes and tree nuts or cow's, sheep's and goat's milk. Most frequent nutritive allergens responsible for over 90% of adverse reactions of this type are proteins of cow's milk, eggs, peanuts, tree nuts, wheat, soy, fish, shellfish, crustaceans, and cephalopods. Allergy intolerance of food antigens is characterized by a very wide spectrum of clinical manifestations. Highly severe systemic reactions, sometimes fatal, are also possible.The diagnosis of food allergy is based on a detailed personal and family medical history, complete clinical examination, and corresponding laboratory and other examinations adapted to the type of hypersensitivity and the character of patient's complaints, and therapy on the elimination diet. A positive effect of elimination diet also significantly contributes to the diagnosis. Although most children "outgrow" their allergies, allergy to peanuts, tree nuts, fish, shellfish, crustaceans, and cephalopods are generally life-long allergies. PMID- 27276870 TI - Foreign scientists on the contribution of Serbian physician and scientist Dr. Lazar K. Lazarevic to medical science. AB - Dr. Lazar K. Lazarevic (1851-1890, Julian calendar/1891, Gregorian calendar) was an exceptional Serbian physician, scientist, writer and translator. During his short life and his close to 11-year-long professional career (1879-1890), Dr. Lazarevic authored 78 scientific papers and presentations in various branches of medicine. His greatest contribution to the field of neurology and to medical science in general is his description of the straight leg raising test.The article titled"Ischiac postica Cotunnii--One contribution to its differential diagnosis"was published in the Serbian language (in Cyrillic alphabet) in the Serbian Archives of Medicine in 1880.The article was translated to German and republished in Vienna in 1884 in Allgemeine Wiener medizinische Zeitung. The straight leg raising test is usually called Lasegue's test/sign, after the French clinician Charles Lasegue, although he never described it. However, there are numerous authors who admit that Lasegue never published the description of the straight leg raising test, and instead give full credits for its discovery to Dr. Lazarevic. Our objective in this article is to highlight the major literature written by foreign scientists who give credit to Dr. Lazarevic for his contribution to medical science. PMID- 27276869 TI - Electrocardiography in pre-participation screening and current guidelines for participation in competitive sports. AB - Electrocardiography (ECG) is especially significant in pre-participation screening due to its ability to discover or to rise a suspicion for certain cardiovascular diseases and conditions that represent a serious health risk in athletes. Common, conditionally benign and training related ECG changes are sinus bradycardia and sinus arrhythmia, first degree atrioventricular block, incomplete right bundle branch block, benign early repolarization, and isolated QRS voltage criteria for left ventricular enlargement. Uncommon ECG changes, unrelated to training, and some specific syndromes are ST segment depression and/or >= 2 mm T wave inversion in two or more adjacent leads, intraventricular conduction disorder, Wolf-Parkinson-White syndrome, long QT interval syndrome, short QT interval syndrome, catecholaminergic polymorphic ventricular tachycardia, monomorphic ventricular extrasystole and benign ventricular tachycardia. Keywords: examination; athletes; recommendations PMID- 27276871 TI - How can eHealth enhance adherence to cancer therapy and supportive care? AB - eHealth is currently a hot topic, but is certainly not a new one. The use of communications technology to relay health-related information or provide medical services has been around since the advent of this technology. It has been primarily over the last decade that eHealth has seen a global expansion, due to the far-reaching capabilities of the Internet and the widespread use of wireless technology. This paper will outline what eHealth is, what adherence is, and how eHealth can help with adherence, in cancer and supportive care particularly. It will discuss the current state of the art, and project into the future. Keywords: telemedicine; compliance; use of electronic media for health PMID- 27276872 TI - Double trouble: accessory spleen mimicking renal carcinoma recurrence identified by scintigraphy. PMID- 27276873 TI - Effectiveness of intervention strategies exclusively targeting reductions in children's sedentary time: a systematic review of the literature. AB - An increasing number of interventions targeting sedentary behaviour in children have emerged in recent years. Recently published reviews included sedentary behaviour and physical activity interventions. This review critically summarizes evidence on the effectiveness of intervention strategies that exclusively targeted reducing sedentary time in children and adolescents. We performed a systematic literature search in Pubmed, Embase and the Cochrane Library through November 2015. Two independent reviewers selected eligible studies, extracted relevant data and rated the methodological quality using the assessment tool for quantitative studies. We included 21 intervention studies, of which 8 studies scored moderate on methodological quality and 13 studies scored weak. Four out of eight moderate quality studies reported significant beneficial intervention effects.Although descriptions of intervention strategies were not always clearly reported, we identified encouragement of a TV turnoff week and implementing standing desks in classrooms as promising strategies. Due to a lack of high quality studies and inconsistent findings, we found no convincing evidence for the effectiveness of existing interventions targeting solely sedentary behaviour. We recommend that future studies apply mediation analyses to explore which strategies are most effective. Furthermore, to increase the effectiveness of interventions, knowledge of children's motives to engage in sedentary behavior is required, as well as their opinion on potentially effective intervention strategies. PMID- 27276874 TI - Pneumococcal colonization and invasive disease studied in a porcine model. AB - BACKGROUND: Streptococcus pneumoniae, a Gram-positive bacterium carried in the human nasopharynx, is an important human pathogen causing mild diseases such as otitis media and sinusitis as well as severe diseases including pneumonia, meningitis and sepsis. There is a strong resemblance between the anatomy, immunology and physiology of the pig and human species. Furthermore, there are striking similarities between S. suis pathogenesis in piglets and S. pneumoniae pathogenesis in humans. Therefore, we investigated the use of piglets as a model for pneumococcal colonization and invasive disease. RESULTS: Intravenous inoculation of piglets with an invasive pneumococcal isolate led to bacteraemia during 5 days, showing clear bacterial replication in the first two days. Bacteraemia was frequently associated with fever and septic arthritis. Moreover, intranasal inoculation of piglets with a nasopharyngeal isolate led to colonization for at least six consecutive days. CONCLUSIONS: This demonstrates that central aspects of human pneumococcal infections can be modelled in piglets enabling the use of this model for studies on colonization and transmission but also on development of vaccines and host-directed therapies. Moreover this is the first example of an animal model inducing high levels of pneumococcal septic arthritis. PMID- 27276875 TI - Characteristics of traditional Chinese medicine users and prescription analysis for pediatric atopic dermatitis: a population-based study. AB - BACKGROUND: Atopic dermatitis among children is an important issue due to relapses and skin manifestations. Traditional Chinese medicine (TCM) is commonly used to treat children with atopic dermatitis. The aim of this study was to investigate the characteristics and TCM prescriptions of patients with atopic dermatitis using a nationwide database. METHODS: Children younger than 12 years of age diagnosed with atopic dermatitis, defined as ICD-9-CM codes 691.8 and 692.x, were identified from the database. Data on age, diagnosis codes, area of residence and use of corticosteroids of the TCM users were recorded. Association rule mining was used to analyze the prescriptions used for atopic dermatitis. RESULTS: We identified 13,646 children with atopic dermatitis using TCM in 2007. Female gender (OR: 0.83 for male gender), adolescence (OR: 10.0, 95 % CI: 8.88 11.15) and allergic rhinitis (OR: 2.44, 95 % CI: 2.10-2.85) were associated with the use of TCM. Fewer of the TCM users were prescribed with corticosteroids (35.8 % of all TCM users), but the TCM users had a higher rate of long-term topical corticosteroid therapy (10.6 % for TCM users versus 2.0 % for those who did not use TCM). Chinese herbal medicine (CHM) was used by 93.7 % of all TCM users in 36,398 prescriptions. On average, 5.6 kinds of CHM were used in combination. The relationship between the CHMs constituted a network, in which Xiao-Feng-San was the core treatment for atopic dermatitis. CONCLUSIONS: In this study, we described the characteristics of children with atopic dermatitis who use TCM in Taiwan. and identified the core CHM treatment. Further research on the safety and efficacy of this treatment are still needed. PMID- 27276876 TI - Organ-sparing treatment of penile cancer with interstitial pulsed-dose-rate brachytherapy. AB - AIM: To assess the efficacy and toxicity profile of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy for penile carcinoma. PATIENTS AND METHODS: From August 2002 to February 2014, 13 men with penile cancer were treated by interstitial brachytherapy. The tumor stage was T1 for eight patients, T2 for four patients, and T3 for one patient. The tumor grade was well differentiated for five patients and moderately differentiated for seven patients, while it was unknown for one patient. Lymph node staging was positive for three of 13 patients. All patients were treated using interstitial PDR brachytherapy with dose specifications according to the Paris system. For data collection of erectile dysfunction, the International Index of Erectile Function questionnaire was used, supplemented by the follow-up data. RESULTS: The median follow-up was 54.0 months (range, 13-155 months). Only one patient (1/13, 7.7 %) with local failure was documented. At 5 and 10 years, the local cumulative recurrence rate, disease-free survival, and the cancer-specific survival rates were 12.5 % (95 % CI, 80.4-119.6), 80.8 % (95 % CI, 75.2-124.8), and 77.9 % (95 % CI, 74.3-125.7), respectively. At the time of analysis, nine of 13 men were alive; two of 13 men died of distant metastases from the tumor and two for other reasons with no sign of cancer disease. Serious late side effects such as soft tissue necrosis occurred in four of 13 patients (30 %) and all were successfully treated with medication. Mutilating salvage surgery was not necessary in any of the cases. Urethral stenosis was documented for two of 13 (15.4 %) and dysuria occurred in four of 13 patients (30.8 %). Eight of 11 men (72.7 %) never or only sometimes had erectile dysfunction. CONCLUSION: In selected patients, interstitial PDR brachytherapy of penile cancer is effective as an organ-sparing treatment. It yields satisfactory results for the conservation of sexual function. PMID- 27276877 TI - The impact of cycle proficiency training on cycle-related behaviours and accidents in adolescence: findings from ALSPAC, a UK longitudinal cohort. AB - BACKGROUND: Cycle accidents are a common cause of physical injury in children and adolescents. Education is one strategy to reduce cycle-related injuries. In the UK, some children undertake National Cycle Proficiency Scheme [NCPS] training (now known as Bikeability) in their final years of primary school. It aims to promote cycling and safe cycling behaviours but there has been little scientific evaluation of its effectiveness. METHODS: The sample (n = 5415) were participants in the Avon Longitudinal Study of Parents and Children who reported whether or not they had received NCPS training. Outcomes were self-reported at 14 and 16 years: cycling to school, ownership of cycle helmet, use of cycle helmet and high visibility clothing on last cycle, and involvement in a cycle accident. An additional outcome, hospital admittance due to a cycle accident from 11 to 16 years, was also included for a subsample (n = 2222) who have been linked to Hospital Episode Statistics (HES) data. RESULTS: Approximately 40 % of the sample had received NCPS training. Trained children were more likely to cycle to school and to own a cycle helmet at both 14 and 16 years, to have worn a helmet on their last cycle at age 14, and to have worn high-visibility clothing at age 16, than those who had not attended a course. NCPS training was not associated with self reported involvement in a cycle accident, and only six of those with HES data had been admitted to hospital due to a cycle accident. Irrespective of training, results indicate very low use of high-visibility clothing, very few girls cycling as part of their school commute, and less than half of helmet owners wearing one on their last cycle. CONCLUSIONS: Our results suggest cycle training courses for children can have benefits that persist into adolescence. However, the low use of cycle helmets, very low use of high-visibility clothing, and low levels of cycling to school for girls, indicate the further potential for interventions to encourage cycling, and safe cycling behaviours, in young people. PMID- 27276878 TI - Different outcomes among favourable and unfavourable intermediate-risk prostate cancer patients treated with hypofractionated radiotherapy and androgen deprivation therapy. AB - BACKGROUND: to evaluate the role of a risk stratification system in intermediate risk prostate cancer (PCa) treated with hypofractionated radiotherapy (HyRT). METHODS: 131 patients affected by intermediate-risk PCa were treated with HyRT at the total dose of 54,75 Gy in 15 fraction plus 9 months of androgen deprivation therapy (ADT). Patients were classified as favourable risk (FIR) if they had a single NCCN intermediate-risk factor (IRF), a Gleason score <=3 + 4 = 7, and <50 % of biopsy cores containing cancer (PBCC). If these criteria were not met were classified as unfavourable risk (UIR). Univariate and multivariate analyses using Cox proportional hazards model were calculated for biochemical recurrence-free survival (bRFS), the risk of local recurrence and metastasis-free survival (MFS). RESULTS: After a median follow-up of 56.7 months (range 9.8 to 93.7 months), 11 patients (8.4 %) died, of whom 2 (1.5 %) for PCa. In the univariate analysis, Gleason score, PPBCs, IRFs and PSA at first follow-up were prognostic factors for bRFS and LF while Gleason score, PPBCs and PSA at first follow-up were significant predictor for MFS. In the multivariate analysis only the PSA at first follow-up resulted a prognostic factor for bRFS and MFS. Patients with a value of PSA at first follow-up <0.7 ng/mL respect to those with PSA >=0,7 ng/mL had a 5y bRFS of 93.3 % vs. 57.5 %, 5y-MFS of 99.0 % vs. 78.9 % and 5y-LF of 5.8 % vs. 38.3 %. Patients in the UIR PCa group with a PSA value <0.7 ng/mL at first follow up had significant better bRFS, LF and MFS. CONCLUSIONS: Risk factors currently not included in the guidelines are useful to stratify patients with intermediate risk PCa in two groups of different prognosis even when HyRT is delivered. PSA at first follow-up is useful in UIR PCa to guide the overall length of ADT. PMID- 27276879 TI - How should we measure global and regional left ventricular systolic function? AB - The assessment of left ventricular (LV) systolic function is frequently the most important task during the echocardiography examination. LV ejection fraction (EF) is the most commonly used measure to assess LV systolic function. EF is well established, with strong prognostic and therapeutic implications, but, nevertheless, it may not always be satisfactory in all patients. Other measures of myocardial contractility can provide valuable additive information in some patients. This is particularly true in patients with suspected heart failure but normal EF. The measurement of longitudinal function using M-mode and/or deformation analysis from tissue Doppler data or speckle tracking algorithms can be useful in this respect. Regional LV dysfunction can be difficult to detect using visual semi-quantitative assessment of regional wall motion. Contrast echocardiography can be most helpful in delineating the LV endocardial border and, thus, increasing sensitivity for detecting wall motion abnormalities. Deformation analysis can also be helpful for detecting subtle wall motion abnormalities, but these methods should be used with caution due to measurement variability and image quality dependence. PMID- 27276880 TI - Effect of catheter ablation on the left ventricular mass index and other echocardiograph parameters in atrial fibrillation patients: comparison with antiarrhythmic drug treatment. AB - BACKGROUND: Catheter ablation (CA) is reported to improve left ventricular (LV) function in patients with atrial fibrillation (AF). This study compared the effects of CA and antiarrhythmic drug treatment (AT) on LV remodeling and other echocardiography parameters in AF. METHODS: We performed a non-randomized prospective study involving 72 drug-resistant AF patients who were treated with either CA (n = 42) or who declined CA and continued on AT (n = 30). Baseline and follow-up (mean 20.7 +/- 7.5 months) echocardiography was performed in all patients. The maintenance of sinus rhythm was determined based on clinical interview, electrocardiography, and 24-h Holter and event recording. RESULTS: There were no significant differences between the two groups in regard to demographic features, blood pressure, and medication. CA was superior to AT with respect to sinus rhythm maintenance, LV ejection fraction, left atrium (LA) diameter, and LA volume index. In addition, CA resulted in decreases in the LV mass [from 190.5 +/- 36.1 to 179.3 +/- 32.4 g (p = 0.02)] and the LV mass index [from 104.2 +/- 20.5 to 98.2 +/- 18.3 g/m(2) (p = 0.03)]. No parameter improved in AT patients. These improved echocardiographic parameters were observed in both groups with maintained sinus rhythm. CONCLUSION: Reverse LV remodeling after CA may include a reduction in the LV mass index, which appears to be associated with sinus rhythm maintenance. PMID- 27276881 TI - Impaired coronary flow reserve in obstructive sleep apnea and its improvement after continuous positive airway pressure therapy: a transthoracic Doppler echocardiographic study. AB - BACKGROUND: It is reported that patients with obstructive sleep apnea syndrome (OSAS) show endothelial dysfunction and that treatment of OSAS by continuous positive airway pressure (CPAP) therapy improves it. OBJECTIVE: In this study we evaluated coronary flow reserve (CFR), which is considered to be affected by coronary microvascular dysfunction, and the change in CFR during treatment of OSAS by CPAP. METHODS: Eleven patients who were diagnosed as having OSAS by polysomnography (PSG) were studied. Phasic coronary flow velocity was obtained in the left anterior descending coronary artery at baseline and during hyperemic conditions with transthoracic 2D echocardiography. CFR was defined as the ratio of hyperemic to basal mean diastolic velocity. CFR was obtained before and after the initiation of CPAP therapy. RESULTS: Coronary flow reserve was decreased (<2.5) in 8 of 11 (73%) patients at baseline. After CPAP therapy, CFR of these 8 patients increased significantly. CONCLUSION: Coronary flow reserve was decreased in 73% of the patients with OSAS and was significantly improved after CPAP therapy. PMID- 27276883 TI - A case of cardiac rupture subsequent to myocardial infarction diagnosed in emergency room. AB - A 72-year-old woman was transferred to the emergency room because of left anterior chest pain with cold sweating. Electrocardiography revealed recent anterior myocardial infarction. Echocardiography showed akinesis of the mid ventricular septum to the apex by apical view, a small amount of pericardial effusion and collapse of the right ventricular wall, indicating cardiac tamponade, by subcostal view. These echocardiographic findings strongly suggested cardiac rupture subsequent to the myocardial infarction. Emergent operation was successfully performed to repair the ruptured left ventricle. PMID- 27276882 TI - Global longitudinal strain by two-dimensional speckle tracking imaging predicts exercise capacity in patients with chronic heart failure. AB - BACKGROUND: Left ventricular ejection fraction (LVEF) predicts mortality in patients with chronic heart failure (CHF). However, a weak correlation was found between LVEF and peak oxygen uptake ([Formula: see text]) in CHF patients. Global longitudinal strain measured by two-dimensional (2D) strain is regarded as a more useful predictor of cardiac events than LVEF. We investigated whether 2D strain obtained at rest could predict peak [Formula: see text] in patients with CHF. METHODS: Fifty-one patients (mean age of 54.0 +/- 12.0 years, 14 females, LVEF 46.0 +/- 15.0%) with stable CHF underwent resting echocardiography and cardiopulmonary exercise testing. Leg muscle strength was measured for the evaluation of peripheral factors. Global longitudinal strain (GLS) in the apical 4-, 3-, and 2-chamber views and global circumferential strain (GCS) in the parasternal mid short-axis view were measured. RESULTS: In all patients, peak [Formula: see text] correlated with leg muscle strength (r = 0.55, p < 0.0001), LVEF (r = 0.46, p < 0.001), GLS (r = -0.45, p < 0.001), and GCS (r = -0.41, p = 0.005), respectively. No significant correlation was found between the ratio of early transmitral velocity to peak early diastolic mitral annulus velocity (E/E') and peak [Formula: see text]. In the patients with heart failure and reduced LVEF, a multiple stepwise linear regression analysis based on leg muscle strength, LVEF, E/E', GLS, and GCS was performed to identify independent predictors of peak [Formula: see text], resulting in leg muscle strength and GLS (R (2) = 0.888) as independent predictors of peak [Formula: see text]. CONCLUSION: Global longitudinal strain at rest could possibly predict exercise capacity, which appeared to be more useful than LVEF, E/E', and GCS in CHF patients with reduced LVEF. PMID- 27276884 TI - Inadvertent left ventricular pacing through a patent foramen ovale diagnosed by trans-thoracic echocardiography. PMID- 27276885 TI - The clinical value of real-time three-dimensional transesophageal echocardiography in the assessment of paravalvular leakage after prosthetic mitral valve replacement. PMID- 27276886 TI - A case of coagula tamponade 4 years after Bentall procedure. PMID- 27276887 TI - Bland-White-Garland syndrome. PMID- 27276889 TI - All eyes on relevance: strategic allocation of attention as a result of feature based task demands in multiple object tracking. AB - Multiple object tracking (MOT) plays a fundamental role in processing and interpreting dynamic environments. Regarding the type of information utilized by the observer, recent studies reported evidence for the use of object features in an automatic, low- level manner. By introducing a novel paradigm that allowed us to combine tracking with a noninterfering top-down task, we tested whether a voluntary component can regulate the deployment of attention to task-relevant features in a selective manner. In four experiments we found conclusive evidence for a task-driven selection mechanism that guides attention during tracking: The observers were able to ignore or prioritize distinct objects. They marked the distinct (cued) object (target/distractor) more or less often than other objects of the same type (targets /distractors)-but only when they had received an identification task that required them to actively process object features (cues) during tracking. These effects are discussed with regard to existing theoretical approaches to attentive tracking, gaze-cue usability as well as attentional readiness, a term that originally stems from research on attention capture and visual search. Our findings indicate that existing theories of MOT need to be adjusted to allow for flexible top-down, voluntary processing during tracking. PMID- 27276888 TI - Transcriptomic analysis illuminates genes involved in chlorophyll synthesis after nitrogen starvation in Acaryochloris sp. CCMEE 5410. AB - Acaryochloris species are a genus of cyanobacteria that utilize chlorophyll (chl) d as their primary chlorophyll molecule during oxygenic photosynthesis. Chl d allows Acaryochloris to harvest red-shifted light, which gives them the ability to live in filtered light environments that are depleted in visible light. Although genomes of multiple Acaryochloris species have been sequenced, their analysis has not revealed how chl d is synthesized. Here, we demonstrate that Acaryochloris sp. CCMEE 5410 cells undergo chlorosis by nitrogen depletion and exhibit robust regeneration of chl d by nitrogen repletion. We performed a time course RNA-Seq experiment to quantify global transcriptomic changes during chlorophyll recovery. We observed upregulation of numerous known chl biosynthesis genes and also identified an oxygenase gene with a similar transcriptional profile as these chl biosynthesis genes, suggesting its possible involvement in chl d biosynthesis. Moreover, our data suggest that multiple prochlorophyte chlorophyll-binding homologs are important during chlorophyll recovery, and light independent chl synthesis genes are more dominant than the light-dependent gene at the transcription level. Transcriptomic characterization of this organism provides crucial clues toward mechanistic elucidation of chl d biosynthesis. PMID- 27276891 TI - International Cooperation of the Japanese Society of Echocardiography: a new friend, Asian-Pacific Association of Echocardiography (AAE). PMID- 27276892 TI - Kinetics of left ventricular rotation during exercise and its relation to exercise tolerance in atrial fibrillation: assessment by two-dimensional speckle tracking echocardiography. AB - BACKGROUND: Left ventricular (LV) rotation plays an important role in cardiac function both at rest and during exercise in sinus rhythm. The kinetics of rotation during exercise and the relation between exercise tolerance and rotation related parameters in patients with atrial fibrillation (AF) are unknown. METHODS: Twenty-nine patients (age 62 +/- 13 years, 6 females) with AF and preserved LV ejection fraction (LVEF) were studied using two-dimensional speckle tracking echocardiography at rest and during exercise with a supine bicycle ergometer (20 W, 10 min). We measured the systolic rotation (Rot) and the peak rotation rate in systole and early diastole (eRotR) at the apical and basal levels of the LV. All patients underwent cardiopulmonary exercise testing to obtain their percent achieved of the predicted peak oxygen consumption (% peak VO2) value. RESULTS: During exercise, apical Rot-related indices were significantly increased only in the preserved % peak VO2 group. In contrast, E/e' was significantly elevated only in the reduced % peak VO2 group. Multivariable stepwise regression analysis showed that apical DeltaRot was independently associated with % peak VO2 (beta = 0.72; p < 0.01). Apical DeltaeRotR, which could not be selected as an independent predictor of % peak VO2, had a good linear correlation with apical DeltaRot (r = 0.81, p < 0.01). CONCLUSIONS: The augmentation of apical rotation in response to exercise may coincide with an increase of the apical derotation rate, and apical rotation reserve may reflect exercise tolerance in patients with AF and preserved LVEF. PMID- 27276893 TI - Developmental changes in the left ventricular diastolic wall strain on M-mode echocardiography. AB - BACKGROUND: The diastolic wall strain (DWS) of the left ventricle has been proposed as an indicator of left ventricular (LV) wall stiffness. The DWS is calculated as follows using M-mode echocardiography:[Formula: see text]Although this index is simple and clinically useful, normal values for children, including neonates, have not been reported. METHODS: The DWS was measured in 235 healthy people, ranging from neonates to adults. They were classified into 8 subgroups according to their age. The DWS was compared with conventional echocardiographic parameters for left ventricle function, including shortening fraction of the left ventricle, the Tei index, E/A of mitral flow, mitral annular tissue Doppler velocity during systole (s') and during early diastole (e'), and the E/e' ratio. RESULTS: The DWS in the just after birth group was 0.28 +/- 0.11, which was significantly lower than that of the remaining groups (p < 0.05), except for the neonate group at 5-10 days after birth. The DWS was highest in the 1-9 years of age group, and then gradually decreased with age. Stepwise regression of various echocardiographic parameters showed that e' was the most relevant parameter for the DWS (beta = 0.64). CONCLUSIONS: Normal values for the DWS of the left ventricle change with age. The data reported in this study can be used as normal values for the DWS of the left ventricle determined by M-mode echocardiography. PMID- 27276895 TI - A case of hypertrophic obstructive cardiomyopathy and acquired von Willebrand syndrome: response to medical therapy. AB - Heyde's syndrome is the combined occurrence of acquired von Willebrand disease caused by aortic valve stenosis and gastrointestinal bleeding that occurs particularly in elderly patients. The bleeding may be linked to the intravascular shear-induced proteolysis of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). Hypertrophic obstructive cardiomyopathy (HOCM) in the left ventricular outflow tract generates a high shear stress condition that can induce such proteolysis. We report the case of a 70-year-old woman with HOCM who had severe anemia and loss of HMWMs. After reduction of the outflow gradient by medical treatment, vWF normalized, and her anemia alleviated. PMID- 27276894 TI - Low diastolic wall strain is associated with raised post-exercise E/E' ratio in elderly patients without obvious myocardial ischemia. AB - BACKGROUND: It has been reported that the diastolic wall strain (DWS) inversely correlates with the myocardial stiffness constant. The ratio of early diastolic transmitral flow velocity to annulus velocity (E/E') correlates with the left ventricular (LV) filling pressure. Increased LV wall stiffness is thought be associated with increased LV filling pressure after exercise. The purpose of this study was to evaluate the correlation between the DWS and post-exercise E/E' in elderly patients without obvious myocardial ischemia. METHODS: Fifty-eight elderly patients (age = 74 +/- 6 years) who underwent treadmill stress echocardiography were studied. All patients had normal LV wall motion at rest, and patients with exercise-induced wall motion abnormality were excluded. The DWS was calculated as follows: DWS = (PWTs - PWTd)/PWTs, where PWTs is the LV posterior wall thickness at end-systole and PWTd is that at end-diastole. As previously reported, DWS <= 0.33 was defined as low DWS and E/E' >=15.0 was defined as a marker of increased LV filling pressure. RESULTS: Eighteen patients had low DWS. Patients with low DWS had greater post-exercise E/E' (17.9 +/- 3.2 vs. 12.8 +/- 3.3, p < 0.0001). The DWS was inversely and strongly correlated with post-exercise E/E' (r (2) = 0.534, p < 0.0001). Low DWS predicted the development of raised post-exercise E/E' >=15.0 with a positive predictive value of 94 % and a negative predictive value of 85 %. CONCLUSION: In elderly patients without obvious myocardial ischemia, the DWS correlates strongly and inversely with post exercise E/E'. Patients with low DWS were likely to develop raised E/E' after exercise. PMID- 27276896 TI - Usefulness of transesophageal echocardiography in diagnosis of hemolytic anemia post total aortic arch replacement using the elephant trunk technique. AB - We report a rare case of a patient with hemolytic anemia who underwent emergency total arch replacement using the elephant trunk technique for type A acute aortic dissection 3 years earlier. The 78-year-old woman was referred to our hospital for diagnosis of the cause of the hemolytic anemia, which required twice weekly blood transfusion. Although contrast-enhanced computed tomography could not provide sufficient information, transesophageal echocardiography (TEE) revealed graft flection with high velocity. After percutaneous balloon dilatation, the hemolytic anemia improved and follow-up TEE showed no re-stenosis of the dilatation site. PMID- 27276897 TI - Intimo-intimal intussusception-circumferential aortic dissection: a rare mechanism of severe acute aortic regurgitation. PMID- 27276898 TI - An unusual cause of left ventricular outflow tract obstruction: obstructive pannus on the left ventricular side of a mechanical mitral prosthesis. PMID- 27276899 TI - Mitral valve thickening in Cogan's syndrome. PMID- 27276900 TI - Right heart serpiginous mass. PMID- 27276901 TI - What do cardiologists know about the safety indexes of echocardiography? PMID- 27276902 TI - Ultrasonic diagnosis of diffuse liver disease. PMID- 27276903 TI - Growth inhibition of neurofibroma by ultrasound-mediated interferon gamma transfection. AB - PURPOSE: We have previously shown that ultrasound-mediated transfection (sonotransfection) can be optimized using a concept based on the ultrasound induced apoptosis produced in our in vitro experiments. At optimized conditions, we have shown, using five cancer cell lines, that sonotransfection is superior to other conventional nonviral methods. Interferon gamma (IFN-gamma) transfection using lipofection has been found to markedly inhibit the proliferation of neurofibroma cell lines. In this study, we investigated whether sonotransfection of IFN-gamma to neurofibroma cell lines can suppress cell proliferation. METHODS: The ultrasound device used was the SonoPore KTAC-4000, which is capable of various acoustic settings. Ultrasound transducers at an oscillation frequency of 1.011 MHz were used; the potential ideal conditions were an intensity of 0.17 W/cm(2) at a burst frequency of 0.5 Hz, 25% duty factor, and 30-s sonication duration. Cells were assayed at 3 and 5 days after sonication. RESULTS: The transfection efficiency was found to be 12%. The ultrasound-treated cells were successfully transfected with IFN-gamma genes as detected by enzyme-linked immunosorbent assay, and the cell growth ratio in the IFN-gamma sonotransfection group tended to be lower than that in the other experimental groups. CONCLUSION: These results suggested that IFN-gamma sonotransfection could potentially become a nonsurgical method for treating skin lesions such as neurofibromas. PMID- 27276904 TI - Construction of artificial promoters sensitively responsive to sonication in vitro. AB - PURPOSE: To develop artificial promoters that are activated in response to sonication and to determine these properties in vitro. METHODS: The binding sites of four transcription factors (nuclear factor-kappa B, activating protein-1, nuclear factor-Y, and CArG element binding factor A) that are activated by oxidative stress were randomly ligated and linked to a TATA-box sequence to control the luciferase gene located downstream. Transiently transfected HeLa cells from human cervical cancer with a plasmid vector containing such a gene cassette were exposed to sonication, and enhancement of luciferase expression was assessed by dual luciferase assay. RESULTS: Of 62 promoters constructed, two promoters, designated clone 31 and clone 62 promoters, showed a more than tenfold enhancement 6 h after sonication with 1-MHz ultrasound at 1.0 W/cm(2) for 60 s. These promoters were activated in a dose-dependent manner with the intensity and duration of sonication. The activation was attenuated by addition of dimethyl sulfoxide, an antioxidant, suggesting that oxidative stress was involved. The clone 31 promoter responded to each of two serial sonications. When sonicated 24 h after the first sonication, the peak of promoter enhancement was higher than that after the first sonication. CONCLUSIONS: A promoter sensitively responsive to sonication was constructed using the above method, possibly leading to the construction of a promoter of interest that could be applied for clinical use. PMID- 27276905 TI - Clinical features and characteristics of blood flow of uterine vascular abnormalities. AB - PURPOSE: The purpose of this study was to assess the clinical features and characteristics of the blood flow in uterine vascular abnormalities using ultrasound and magnetic resonance imaging (MRI). METHODS: A total of 17 women were diagnosed with uterine vascular abnormalities by ultrasound. The clinical characteristics of the patients and the distribution and waveform of the intrauterine vessels were examined using transvaginal gray-scale and Doppler ultrasonography, spin-echo MRI, and MR angiography. RESULTS: The average age of the 17 subjects was 44.3 years, and 5 were postmenopausal women. The number of pregnancies and deliveries was 2.0 and 1.7, respectively. Of the 17 subjects, 7 had a moderate or severe grade of dysmenorrhea and 7 had a history of vascular disease. In all subjects, vaginal ultrasound demonstrated tubular or numerous tortuous anechoic areas in the uterine wall, and Doppler ultrasound showed that the tubular or numerous dilated tortuous vessels had an atypical wave flow, unlike that of an artery or a vein. The distribution of displayed flow varied, and the waveforms of the Doppler ultrasound displayed three patterns. The averages of the pulse Doppler flow indices showed low impedance in the abnormal uterine vessel and the uterine artery, especially in cases of true arteriovenous malformations. MR angiography demonstrated distinct, tortuous, and coiled vascular channels in the pelvis during and just after the arterial phase. CONCLUSION: Characterization of the clinical features of uterine vascular abnormalities is considered to be valuable for obstetricians and gynecologists. PMID- 27276906 TI - A case of dermoid cyst of the floor of the mouth: ultrasonography was more useful than computed tomography and magnetic resonance imaging in the preoperative diagnosis. AB - Dermoid cysts are rare in the floor of the mouth. This report presents a case of dermoid cyst (dermoid type) of the floor of the mouth in a 21-year-old man. The preliminary preoperative assessment was made by using three modalities: computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonography (US). CT depicted the lesion as a well-circumscribed, unilocular, homogeneous low-density mass. MRI showed a mass lesion located in the submental region between the geniohyoid and mylohyoid muscles. The lesion exhibited homogeneous intermediate signal intensity on T1-weighted images and homogeneous high signal intensity on T2-weighted images. The wall of the lesion was well enhanced on gadolinium enhanced MRI. CT and MRI could not demonstrate any fatty components within the lesion and only indicated that the lesion was cystic in nature. In contrast, on US, multiple echogenic foci that seemed to be caused by keratin and sebaceous material were detected within the lesion, and this US finding was useful information for the differential diagnosis. In this case, of the three modalities, only US suggested that the lesion might be a dermoid cyst. PMID- 27276907 TI - Xanthogranulomatous pyelonephritis in children: diagnostic and therapeutic aspects. AB - Xanthogranulomatous pyelonephritis (XGP) is a rare, chronic inflammatory disease of the kidneys. It is characterized by destruction of renal parenchyma and accumulation of lipid-laden foamy macrophages. Diffuse and focal forms are known. The condition is mainly observed in middle-aged women, and it is very rare in childhood. Of 32 nephrectomies carried out in children for various diseases in our hospital over the course of 2 years, there were two cases of diffuse XGP. In both cases, the preoperative diagnosis based on ultrasound findings was highly suggestive of XGP. We present the two cases and define the typical ultrasonographic signs for distinguishing XGP from other renal masses. The diagnostic and therapeutic management is discussed and an overview of the literature is given. PMID- 27276908 TI - Glycogen-rich clear cell carcinoma of the breast: a case report. AB - Glycogen-rich clear cell carcinoma (GRCC) of the breast is a rare malignant breast tumor. We recently encountered a case of GRCC and report our imaging findings here. The patient was a 49-year-old woman with a mass in her right breast. Mammographic study showed no definite mass shadow because the breast was dense. No calcifications were identified. Ultrasonography disclosed a hypoechoic mass that had a diameter of 1.3 cm, partially irregular borders, heterogeneous internal echoes, and posterior acoustic enhancement, suggesting an invasive carcinoma. Histologic study of core needle biopsy specimens showed a solid proliferation of large clear carcinoma cells, suggestive of a ductal carcinoma. The carcinoma cells possessed clear cytoplasm larger than that typical of ductal carcinoma cells. Breast-conserving surgery was performed with axillary sentinel lymph node biopsy. Macroscopically, the tumor was a solid, white-yellow mass with fairly well defined margins. Histologic examination of the tumor showed a characteristic feature of GRCC: the tumor cells were positive for estrogen receptor but negative for progesterone receptor and Her 2, and the sentinel lymph node was histologically negative. The patient remains well and has had no clinical recurrence of the disease after 2.5 years of follow-up without radiotherapy or adjuvant therapy. Noteworthy is the usefulness of mammography and ultrasonography, which should be used as complementary imaging tools. PMID- 27276909 TI - Ultrasonographic findings of renal arteriovenous malformations. PMID- 27276910 TI - Roles of three AbrBs in regulating two-phase Clostridium acetobutylicum fermentation. AB - Clostridium acetobutylicum is an important industrial microorganism for n-butanol bioproduction, and its transcription factor AbrB0310 regulates various important cellular processes. However, the roles of two abrB homologues, abrB1941 and abrB3647, have not been determined because they appear inactive during transcription. Here, we performed a detailed investigation into the function of abrB1941 and abrB3647 in C. acetobutylicum. Interestingly, we observed that AbrB3647 exerts an important influence on biphasic fermentation that opposes the influence of AbrB0310, while AbrB1941 might not be essential. When abrB3647 was disrupted using the Targetron system, a greatly improved cellular growth occurred. The following analysis shows that all three AbrBs participated in metabolically regulating acidogenesis, solventogenesis, and a two-phase transition in C. acetobutylicum, but the AbrB0310 and AbrB3647 functions were the most important. Moreover, the target genes subject to AbrB0310 and AbrB3647 regulation closely overlap. Based on these results, we will better understand the roles of the three AbrBs in regulating solventogenic clostridia cell physiology. PMID- 27276912 TI - Robot-assisted excision of cervical cystic hygroma through a retroauricular hairline approach: a case report. AB - BACKGROUND: Cystic hygroma is a rare benign abnormality of the lymphatic system generally occurring in young children less than 2 years old. The standard transcervical surgical treatment of cystic hygroma may often leave a permanent scar in the neck region. CASE PRESENTATION: We report a case of cystic hygroma in a 19-month-old Asian baby girl successfully treated with robot-assisted excision through a hairline neck-lift approach. We present the use of the Yang's retractor as an instrumental advancement to this surgical approach. CONCLUSIONS: Treatment options for cystic hygroma may be surgical or nonsurgical. We report a case of cystic hygroma in a 19-month-old child successfully treated with robot-assisted excision through a small concealed retroauricular hairline approach. This is the first report in the medical literature of treating cystic hygroma with a minimally invasive robot-assisted excision via a small, concealed, hairline incision. PMID- 27276911 TI - Enzymatic synthesis of bioactive compounds with high potential for cosmeceutical application. AB - Cosmeceuticals are cosmetic products containing biologically active ingredients purporting to offer a pharmaceutical therapeutic benefit. The active ingredients can be extracted and purified from natural sources (botanicals, herbal extracts, or animals) but can also be obtained biotechnologically by fermentation and cell cultures or by enzymatic synthesis and modification of natural compounds. A cosmeceutical ingredient should possess an attractive property such as anti oxidant, anti-inflammatory, skin whitening, anti-aging, anti-wrinkling, or photoprotective activity, among others. During the past years, there has been an increased interest on the enzymatic synthesis of bioactive esters and glycosides based on (trans)esterification, (trans)glycosylation, or oxidation reactions. Natural bioactive compounds with exceptional theurapeutic properties and low toxicity may offer a new insight into the design and development of potent and beneficial cosmetics. This review gives an overview of the enzymatic modifications which are performed currently for the synthesis of products with attractive properties for the cosmeceutical industry. PMID- 27276914 TI - Recommended Ethical Safeguards on Fertilization of Human Germ Cells Derived from Pluripotent Stem Cells Solely for Research Purposes. AB - Production of human fertilized embryos by using germ cells derived from pluripotent stem cells (PSCs) entails ethical issues that differ fundamentally depending on the aim. If the aim is solely to conduct research, then embryo generation, utilization and destruction must respect for the human embryo as having the innate potential to develop into a human being. If the aim is human reproduction, this technology must never be used to manipulate human life, confuse social order, or negatively affect future generations. Researchers should distinguish the aims and then accordingly establish a consensus on the safeguards needed to proceed with scientifically significant and socially accepted research, or otherwise set a moratorium. Currently, in Japan, germ cell production from human PSCs is permitted, whereas fertilization of these germ cells is not. The Japanese Expert Panel on Bioethics in the Cabinet Office has proposed that all of the following conditions must be met to approve fertilization for research purposes: (1) the research is significant for the life sciences and medicine; (2) the benefits or anticipated benefits are socially accepted; (3) human safety is assured; and (4) safeguards are put in place. If fertilization is ethically approved, I recommend the following safeguards: limitation of the purpose to improving conventional ART as an initial step; permitted culture of human embryos until the appearance of the primitive streak; restriction of the number of embryos produced to the minimum necessary; prohibition of transplantation into a human or animal uterus; and provision of human-derived ova that are not required for ART treatment. PMID- 27276913 TI - Risk prediction to inform surveillance of chronic kidney disease in the US Healthcare Safety Net: a cohort study. AB - BACKGROUND: The capacity of electronic health record (EHR) data to guide targeted surveillance in chronic kidney disease (CKD) is unclear. We sought to leverage EHR data for predicting risk of progressing from CKD to end-stage renal disease (ESRD) to help inform surveillance of CKD among vulnerable patients from the healthcare safety-net. METHODS: We conducted a retrospective cohort study of adults (n = 28,779) with CKD who received care within 2 regional safety-net health systems during 1996-2009 in the Western United States. The primary outcomes were progression to ESRD and death as ascertained by linkage with United States Renal Data System and Social Security Administration Death Master files, respectively, through September 29, 2011. We evaluated the performance of 3 models which included demographic, comorbidity and laboratory data to predict progression of CKD to ESRD in conditions commonly targeted for disease management (hypertension, diabetes, chronic viral diseases and severe CKD) using traditional discriminatory criteria (AUC) and recent criteria intended to guide population health management strategies. RESULTS: Overall, 1730 persons progressed to end stage renal disease and 7628 died during median follow-up of 6.6 years. Performance of risk models incorporating common EHR variables was highest in hypertension, intermediate in diabetes and chronic viral diseases, and lowest in severe CKD. Surveillance of persons who were in the highest quintile of ESRD risk yielded 83-94 %, 74-95 %, and 75-82 % of cases who progressed to ESRD among patients with hypertension, diabetes and chronic viral diseases, respectively. Similar surveillance yielded 42-71 % of ESRD cases among those with severe CKD. Discrimination in all conditions was universally high (AUC >=0.80) when evaluated using traditional criteria. CONCLUSIONS: Recently proposed discriminatory criteria account for varying risk distribution and when applied to common clinical conditions may help to inform surveillance of CKD in diverse populations. PMID- 27276916 TI - Beneficial Effects of Magnesium Treatment on Heart Rate Variability and Cardiac Ventricular Function in Diabetic Rats. AB - BACKGROUND: Diabetes mellitus induces life-threatening cardiovascular complications such as cardiac autonomic neuropathy and ventricular dysfunction and is associated with hypomagnesemia. In this study, we investigated the short term effects of magnesium (Mg2+) treatment on streptozotocin (STZ)-induced diabetic cardiac complications. METHODS: Adult Wistar rats were treated once with STZ (50 mg/kg, intraperitoneally [ip]) or vehicle (citrate) and then daily for 7 days with MgSO4 (270 mg/kg, ip) or saline. On the eighth day, in vivo tail-pulse plethysmography was recorded for heart rate variability (HRV) analysis, and ex vivo Langendorff-based left ventricular (LV) pressure-volume parameters were measured using an intraventricular balloon. Measurements of plasma lipid and Mg2+ levels as well as blood glucose and cardiac tissue Mg2+ levels were also performed. RESULTS: Treatment with Mg2+ prevented diabetes-induced alterations in the standard deviation of the averages of normal-to-normal (NN) intervals (SDANN), root mean square differences of successive NN intervals (RMSSD), heart rate, and low-frequency (LF) power-high-frequency (HF) power ratio. In addition, Mg2+ restored orthostatic stress-induced changes in SDANN, RMSSD, and LF-HF ratio in diabetic rats. In isolated hearts, Mg2+ reversed the diabetes-induced decrease in LV end-diastolic elastance and the right shift of end-diastolic equilibrium volume intercept, without altering LV-developed pressure or end-systolic elastance. However, Mg2+ did not prevent the elevation in blood glucose, total cholesterol, and triglycerides or the decrease in high-density lipoprotein cholesterol in diabetes. Plasma- or cardiac tissue Mg2+ was not different among the treatment groups. CONCLUSION: These results suggest that Mg2+ treatment may attenuate diabetes-induced reduction in HRV and improve LV diastolic distensibility, without preventing hyperglycemia and dyslipidemia. Thus, Mg2+ may have a modulatory role in the early stages of diabetic cardiovascular complications. PMID- 27276915 TI - Markers of Hippo-Pathway Activity in Tumor Forming Liver Lesions. AB - Hepatocellular Carcinoma (HCC) is a lethal cancer worldwide. Recently, the hippo signaling pathway has been implicated in tumorigenesis of HCC and other malignant tumors. Aim of the study was therefore to evaluate the hippo signaling pathway activity and its clinico-pathological associations and crosstalk in different tumor forming hepatocellular lesions (HCC, hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH) and cirrhosis). A tissue micro array (TMA) from paired human tumorous and non-tumorous (NT) tissue samples of HCC (n = 92), HCA (n = 25), FNH (n = 28) and cirrhosis (n = 28; no NT) was constructed. The hippo pathway related proteins of MST1/2, (nuclear(n)/cytoplasmic(c)) YAP and (phospho(p)) TAZ and interactors as Glypican3, RASSF1a, pAKT, pERK and pP70S6K were evaluated by immunohistochemistry (IHC). Proliferation was assessed by Ki67 IHC and apoptosis by TUNEL-technique. MST1/2- and nYAP-immunoreactivity was associated with lymph node status (p = 0.048, p = 0.001), higher grading (p = 0.012, p = 0.24) and unfavorable relapse-free survival (p = 0.004, p = 0.003). MST1/2, c/nYAP and pTAZ were significantly different between HCC/NT (p < 0.001, p = 0.029, p < 0.001, p < 0.001) and mono-/polyclonal hepatocellular lesions (HCC/HCA vs. FNH/cirrhosis; all p <= 0.001). Phospho-TAZ-negativity and nYAP positivity were almost exclusively and MST1/2 exclusively detected in HCC. MST1/2 correlated with pP70S6K (p = 0.002), pERK (p = 0.042), RASSF1a-IRS (p = 0.002) and GPC3 (p < 0.001) and nYAP with GPC3 (p = 0.025), higher Ki67-indices (p = 0.016) and lower apoptosis rate (p = 0.078). MST1/2 and nYAP are unfavorable prognostic markers associated with an aggressive tumor-phenotype in HCC. Positive nYAP- and negative pTAZ-immunostaining were strong indicators of a monoclonal hepatocellular lesion. The unexpected findings for MST1/2 remain to be elucidated. PMID- 27276917 TI - Good papers, bad papers. PMID- 27276918 TI - Amlodipine has a preventive effect on temporal left ventricular hypokinesia after emotional stress compared with an angiotensin II receptor blocker. AB - PURPOSE: We previously reported that alpha- and beta-blockers protected against emotional stress-induced cardiac dysfunction, but the protective effects of other antihypertensive drugs is unknown. The purpose of this study is to evaluate the ability of a calcium channel blocker, amlodipine, to prevent temporal left ventricular hypokinesia after emotional stress compared with an angiotensin II receptor blocker, olmesartan medoxomil. METHODS: Rats premedicated with amlodipine (0.2 mg/kg), olmesartan (0.8 mg/kg), or vehicle were restrained for 30 min (immobilization stress: IMO) to reproduce emotional stress and then anesthetized to release stress. We measured the fractional area change (FAC) using echocardiography (SONOS5500) with a s12 probe (frequency 5-12 MHz, frame rate 120 Hz) and blood pressure and heart rate at the end of IMO and every 10 for 60 min after IMO. RESULTS: During IMO, FAC in the amlodipine or the olmesartan group was as high as that in the vehicle group. At 20 min after IMO, FAC in the amlodipine group was significantly higher than in the other two groups (84 +/- 8 vs. 60 +/- 7 or 68 +/- 15 %, p < 0.05). During IMO, blood pressure in the amlodipine or the olmesartan group was significantly lower than with vehicle (119 +/- 6 and 110 +/- 7 vs. 124 +/- 5 mmHg, p < 0.05). After IMO, blood pressure in the olmesartan group was significantly lower than in the other two groups. CONCLUSION: Acute administration of amlodipine could prevent a sudden drop in cardiac function after acute stress like IMO, but olmesartan did not. Amlodipine might have a protective effect on temporal left ventricular hypokinesia after emotional stress, which might not be related to decreased blood pressure. PMID- 27276919 TI - Experimental evaluation of portal venous pulsatile flow synchronized with heartbeat intervals: effects of vascular clamping on portal hemodynamics. AB - PURPOSE: We previously showed that blood flow in the portal vein was pulsatile and influenced by both the inferior vena cava and the arterial system in a complex manner (Nihei et al., 38:141-149, 2011). The objective of the present study is to identify determinants of blood flow and to clarify the source of pulsatile flow in the portal vein. METHODS: Three-breed terminal crossbreed mini pigs underwent general anesthesia. Pressure and flow in the portal vein, inferior vena cava, hepatic artery, and mesenteric artery were measured simultaneously. Vascular occluders were placed in the inferior vena cava, hepatic artery, and mesenteric artery to examine the effects of clamping on portal venous flow. RESULTS: Clamping of the mesenteric artery altered pressure and flow waves in the portal vein to waveforms similar to those in the inferior vena cava. Waves resembling those of the inferior vena cava superimposed on portal venous flow appeared later than waves of the inferior vena cava. Clamping of the inferior vena cava promptly altered portal venous pressure and flow. Because clamping of the inferior vena cava led to a sharp rise in portal venous pressure, detailed evaluations were not feasible. Clamping of the hepatic artery had no effect on flow-wave pulsation in the portal vein. CONCLUSIONS: In the hepatic circulation, flow-wave pulsation in the portal vein is influenced by flow in the inferior vena cava via the sinusoids and by flow in the mesenteric artery via the capillary vessels of the intestine. PMID- 27276920 TI - Sonographically guided puncture of the pancreas: incidence of complications, and risk factors. AB - PURPOSE: Data yielded by transabdominal ultrasound-guided puncture techniques are valuable for determining the malignancy of inoperable mass lesions of the pancreas. In this study we analyzed the incidence of complications and the risk factors. METHODS: A total of 430 punctures of the pancreas were performed for 281 patients. Risk factors were prospectively assessed and complications were recorded. All punctures were sonographically guided. RESULTS: The 281 patients underwent a total of 351 puncture procedures including 430 punctures and 901 passes. The maximum diameter of the pancreatic mass lesion was documented; the mean diameter was 48.3 +/- 29.1 mm. 75.8 % of punctures were performed with a needle diameter of 0.7-0.95 mm, and 23.0 % of punctures were performed as cutting biopsies producing a tissue sample 1.2 or 1.6 mm in diameter. In 77.8 % of punctures, one puncture was performed, and in 21.9 %, two punctures were performed. Three punctures were performed for one patient (0.3 %) only. The incidence of major complications was 0.3 %. None of the assessed risk factors was associated with an elevated incidence of complications. CONCLUSION: Our findings demonstrate the safety of transabdominal percutaneous puncture of the pancreas but do not enable conclusions to be drawn with regard to individual risk factors. PMID- 27276921 TI - Ultrasonography of tubular ectasia of the rete testis with associated scrotal findings. AB - PURPOSE: Tubular ectasia of the rete testis (TERT) is a rare disorder that can be seen on ultrasonography (US) during a routine examination. In this study, we aim to discuss 15 cases of TERT and concomitant scrotal pathologies. METHODS: A total of 405 patients who were admitted to our department between March 2009 and December 2011 for scrotal US with different complaints such as scrotal pain, palpable mass, infertility, varicocele, or hydrocele were evaluated. Presence or absence of TERT and associated scrotal anomalies if TERT was present were considered on gray-scale US and color Doppler US. RESULTS: Tubular ectasia of the rete testis was detected in 15 patients (3.7 %). It was unilateral in eleven patients (73.3 %) and bilateral in four patients (26.7 %). The mean age of the patients with TERT in this study was 43.7 years (range 24-85 years). Five patients (33.3 %) with TERT presented with infertility, four of them (26.7 %) presented with palpable mass, and six of them (40%) were admitted with scrotal pain. In 14 patients (93.3 %), at least one of the following disorders associated with TERT was seen: epididymal cyst, spermatocele, hydrocele, and varicocele. CONCLUSION: Tubular ectasia of the rete testis shows characteristic appearances on gray-scale and Doppler US evaluation, and no other modality is necessary for diagnosis. TERT is usually associated with epididymal pathologies such as epididymal cyst or spermatocele located on the same side. Testicular neoplasms, intratesticular varicocele, and cystic dysplasia of the testis should be considered in the differential diagnosis of TERT. PMID- 27276922 TI - Dynamic power Doppler ultrasonography of anterior abdominal wall hernias: confirmation of incarceration. AB - PURPOSE: Power Doppler ultrasonography (PD-US) is a motion-sensitive modality that can display flow characteristics regardless of the direction. This increased motion sensitivity can be used as a parameter to show the tissue motion on artificially generated fremitus images. This study aimed to confirm any signs of incarceration in abdominal wall hernias proven by herniorrhaphy by examination with dynamic PD-US (during manual compression-decompression maneuvers). METHODS: Twenty-seven patients with anterior abdominal wall hernia with a narrow neck (<1 cm in diameter) were examined firstly with gray-scale ultrasonography (GS-US), and then with dynamic PD-US. Two independent radiologists, who were blinded to the real-time images showing the orientation and motion of the hernia neck, completed the examinations. These images were evaluated for any signs of incarceration, as well as the orientation of the hernia neck. RESULTS: Orientations of the hernia neck were not described on GS-US images in 13 lesions and on dynamic PD-US images in 3 lesions. While the GS-US examination revealed incarcerated hernia in four of the patients, the dynamic PD-US examination revealed an additional seven patients with symptoms associated with incarceration. CONCLUSION: Dynamic PD-US may show the orientation of the hernia neck and any sign of incarceration more accurately and clearly than conventional GS-US. Being informed about these features preoperatively is of utmost importance. Thus, anterior abdominal wall hernias should be examined by dynamic PD-US. PMID- 27276923 TI - Case-control study of the RFA therapeutic effect of newly developed 4D US and conventional 2D US. AB - PURPOSE: For radiofrequency ablation (RFA) therapy of hepatocellular carcinoma (HCC), accurate positioning of the inserted needle in the index tumor seems to be an important factor affecting therapeutic effect. In a case-control study, we compared the therapeutic effect of RFA using 4D and 2D ultrasonography (US) to evaluate whether 4D US is more effective. METHODS: Twenty subjects treated with percutaneous RFA using 4D US (4D group) and 20 subjects using conventional 2D US (2D group), who were matched for age, sex, and HCC diameter, were enrolled in this study. Aplio XG was used as the US system and PVT-375MV as the newly developed 4D US probe. The therapeutic effect of RFA was classified into four grades (A-D: "Grade A" is "absolutely curative"). RESULTS: In the 2D group, Grade A was achieved in 12 subjects (60 %). In contrast, Grade A was achieved in 19 subjects (95 %) in the 4D group. The proportion of cases in which Grade A was achieved was significantly higher in the 4D group (P < 0.01). CONCLUSIONS: By using a 4D US device for RFA, more accurate insertion could be achieved and more effective therapy could be performed. PMID- 27276924 TI - A case of focal nodular hyperplasia with a new characteristic finding on contrast enhanced ultrasonography using Levovist. AB - We used contrast-enhanced ultrasound with Levovist, a microbubble contrast agent, to diagnose a case of hepatic focal nodular hyperplasia (FNH). A new characteristic finding of heartbeat-synchronized centrifugal enhancement was discovered. We call this enhancement pattern the "sonographic fireworks sign." It is expected to be useful for diagnosing FNH, especially when the lesions are small and it is difficult to depict a spoke-wheel pattern. PMID- 27276925 TI - Appendiceal mucocele and peritoneal inclusion cyst mimicking right adnexal masses: a diagnostic challenge in gynecologic practice. AB - Mucocele of the appendix (MA) is an uncommon disease. Preoperative differential diagnosis of MA and a peritoneal inclusion cyst (PIC) from gynecologic diseases is still a challenge. We herein report a very rare case with MA and PIC. As far as we know, this is the first report of a case having MA and PIC found simultaneously at surgery. A 31-year-old woman complained of lower abdominal pain and high fever. Based on her symptoms and laboratory tests, pelvic inflammatory disease (PID) was considered to be the most probable diagnosis. She underwent antibiotics therapy and her conditions subsided. However, ascites reappeared in a month, and ultrasound and MRI demonstrated a right ovarian cyst and a suspected right hydrosalpinx. Laparotomy revealed large PIC and MA with normal bilateral adnexa. Patients with an adnexal mass or symptoms suggesting PID should be examined carefully considering such conditions in a daily gynecologic practice. PMID- 27276926 TI - Prenatal diagnosis of intracranial immature teratoma in the third trimester using 2D and 3D sonography. AB - Intracranial tumors are uncommon and represent 0.5-1.5 % of all pediatric tumors. Teratoma is the most frequent intracranial tumor found at birth. Large teratomas are extremely rare and have a guarded prognosis since they grow fast and cause brain tissue destruction. A 31-week primigravida was referred to our hospital for investigation of an intracranial mass seen in the fetus. Two-dimensional ultrasound showed a large heterogeneous solid mass with calcifications inside, measuring 5.3 * 4.8 cm. It was in the right cerebral hemisphere at the level of the middle and posterior fossa, thereby shifting the midline and causing severe ventriculomegaly that measured 3.5 cm at the level of the lateral ventricle. Three-dimensional ultrasound (3DUS) in multiplanar mode allowed us to assess the anatomical relationships between the mass and the midline structures. The neurosurgical team, who had suspected that the case was inoperable, was thus able to gain a better understanding of the case. Transfontanellar ultrasound was performed on the day after the birth and confirmed the previous findings. Moreover, a biopsy confirmed the histology of the mass: it was an immature teratoma. The infant died on the 24th day of life after a large expansion of head circumference. Intracranial teratomas are extremely severe because of their quick growth and mass effect, often leading to neonatal death within days. 3DUS is a new prenatal diagnostic method that makes it possible to assess the anatomical relationships between the mass and the intracranial structures, thus enabling better preoperative planning. PMID- 27276928 TI - Radiologic findings of a giant unilateral abdominoscrotal hydrocele associated with undescended testis. AB - Abdominoscrotal hydrocele (ASH) is an uncommon entity characterized by an hourglass-shaped hydrocele that extends from the scrotum into the abdominal cavity. In this case, ultrasonography and computed tomography findings of an 11 month-old patient with a right ASH and undescended testis are reported. PMID- 27276927 TI - Prenatal ultrasound and magnetic resonance imaging findings of a hypovascular epignathus with a favorable prognosis. AB - Epignathus of a fetus is an extremely rare type of an oropharyngeal teratoma that commonly arises from the palate and often grows in the prenatal period, leading to polyhydramnios due to difficulty in swallowing before birth and a high mortality due to the airway obstruction after birth. We report here a very rare case of a fetus with an epignathus decreasing in size naturally in the prenatal period with a favorable prognosis. In contrast to previously reported cases of epignathus that grew rapidly in the prenatal period, color Doppler fetal ultrasound showed a hypovascular tumor in our case. Moreover, histopathologic examination revealed an epignathus with necrotic areas inside. Based on our experience, a hypovascular epignathus demonstrated by color Doppler fetal ultrasound may be an indicator of a favorable prognosis. PMID- 27276929 TI - US and color Doppler findings in angiolymphoid hyperplasia with eosinophilia involving the superficial temporal artery. AB - Reported here is a 60-year-old man with multiple localizations of angiolymphoid hyperplasia with eosinophilia (ALHE) in the temporal region, involving the superficial temporal artery, detected and analyzed with ultrasound and color Doppler. The usefulness of this diagnostic technique and the peculiar signs of ALHE are discussed. PMID- 27276930 TI - Hepatic parenchymal hemodynamics of cholangitis with portal trunk thrombus using contrast-enhanced ultrasonography with Sonazoid: delineation of so-called central and peripheral zonal differentiation by arrival-time parametric imaging. AB - We carried out contrast-enhanced ultrasonography using Sonazoid for a patient who had portal thrombosis due to choledocholith and cholangitis, and the video images were analyzed by an offline procedure using arrival-time parametric imaging. Colors were changed with the time course from red to orange, yellow, green, light blue, and blue, with the time the contrast agent reached the right hepatic artery as the starting point. The central part of the liver was primarily colored blue, and the peripheral part primarily yellowish-green. In other words, we confirmed the central and peripheral zonal differentiation observed in the arterial phase of dynamic computed tomography by color mapping image of arrival-time parametric imaging. Particularly, real-time changes in the hemodynamics of the hepatic parenchyma could be captured by color mapping image using arrival-time parametric imaging. PMID- 27276931 TI - "Double eyes" sign of congenital bilateral dacryocystoceles. AB - Dacryocystocele is caused by nasolacrimal duct obstruction and results in cystic dilatation of the proximal part of the nasolacrimal duct, which is located inferomedial to the orbit, leading to fluid accumulation. It is important to consider that persistent congenital bilateral dacryocystoceles may cause neonatal nasal obstruction resulting in respiratory difficulty, and large dacryocystoceles may require surgical drainage. Ultrasonography demonstrates that congenital bilateral dacryocystoceles and normal eyeballs prenatally resemble two pairs of cystic "lesions" of different sizes. We herein present a case of prenatally diagnosed isolated congenital bilateral dacryocystoceles and propose the new name of "double eyes" sign for this rare condition to create an impact on medical students and residents. PMID- 27276932 TI - Contrast-enhanced ultrasonography using Sonazoid((r)) is useful for diagnosis of malignant ovarian tumors: comparison with Doppler ultrasound. AB - PURPOSE: The purpose of this study was to assess the usefulness of Sonazoid((r)) enhanced ultrasonography (US) in the diagnosis of ovarian cancer in comparison with Doppler US. METHODS: Twenty-five ovarian tumor patients who were scheduled to undergo surgery were recruited for this study. The day before the operation, each patient was evaluated with color and power Doppler and baseline US during intravenous infusion of Sonazoid. Each lesion was classified as "benign" or "malignant" on the basis of specific criteria for a Doppler signal or Sonazoid enhanced pattern. The reference standard was the histology of surgically removed adnexal tumors. RESULTS: Twenty patients were diagnosed with malignant tumors (invasive cancer, n = 15; metastatic cancer, n = 1; borderline tumor, n = 4), and the remaining five were diagnosed with benign tumors. Sonazoid-enhanced US correctly depicted the presence or absence of intratumoral blood flow in all patients with an accuracy of 92 %. Color Doppler ultrasound depicted the malignancies with an accuracy of 64 %, and power Doppler ultrasound depicted them with an accuracy of 76 %. CONCLUSION: Our study suggests that Sonazoid-enhanced US is superior to conventional color Doppler US for the diagnosis of malignant ovarian tumors, but not to power Doppler US. The data and their interpretation in our study should be taken with some degree of caution because of the small number of subjects. Further studies involving a larger sample size would be needed to confirm these findings. PMID- 27276933 TI - Prenatal diagnosis of congenital syngnathia by 3D ultrasound and pathological correlation. AB - Congenital syngnathia is a maxillomandibular fusion, and it can vary in severity from single mucosal bands (synechiae) to complete bony fusion (synostosis). Cases of combinations of bony or soft tissue adhesions between the mandible and maxilla with cleft of the lip or palate, aglossia, popliteal pterygium, and van der Woude syndrome have been reported. It is a very rare condition, with only one case report of prenatal diagnosis using two-dimensional ultrasound in the literature. We present the first case of prenatal diagnosis of congenital syngnathia by three dimensional ultrasound and the postnatal pathology correlation. PMID- 27276934 TI - The Clinical Utility of Next Generation Sequencing Results in a Community-Based Hereditary Cancer Risk Program. AB - Since the 2013 Supreme Court ruling on BRCA1/BRCA2 patenting, hereditary cancer gene panels now include BRCA1 and BRCA2, making these panels an option for first tier testing. However, questions remain about the clinical utility and implications of these panels for medical management with inclusion of genes of unknown to moderate penetrance. To better understand how use of these panels affected our practice, we reviewed patients who underwent testing in our clinic from July 1, 2013 through May 23, 2014. Indications for testing included personal and/or family history of breast and/or ovarian cancer. A total of 136 patients underwent panel testing via a single commercial laboratory; 12 (8.8 %) patients were positive for a pathogenic or likely pathogenic mutation (four BRCA2 mutations, two TP53 mutations, one CDH1 mutation, two ATM mutations, and one patient each with a CHEK2, NBN, or PALB2 mutation). Of these positive patients, 100 % met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer genetic testing (2.2014). Mutations in seven of twelve (58 %) patients led to changes in medical management; three of seven (43 %) had a non-BRCA1 or BRCA2 gene mutation. Our findings suggest that there is clinical utility of panels that include genes of unknown to moderate penetrance. PMID- 27276937 TI - Communication: Proper use of broken-symmetry calculations in antiferromagnetic polyradicals. AB - The present comment formulates some recommendations regarding the use of broken symmetry Unrestricted Density Functional Theory (UDFT) solutions in those polyradical architectures predicted to be of ground-state singlet character according to Ovchinnikov's rule. It proposes a procedure to identify the number of open shells, to reach the relevant Ms = 0 solution, and to estimate the low energy spectrum of the states which keeps this number of open shells. PMID- 27276935 TI - Evaluating biochemical methane production from brewer's spent yeast. AB - Anaerobic digestion treatment of brewer's spent yeast (SY) is a viable option for bioenergy capture. The biochemical methane potential (BMP) assay was performed with three different samples (SY1, SY2, and SY3) and SY1 dilutions (75, 50, and 25 % on a v/v basis). Gompertz-equation parameters denoted slow degradability of SY1 with methane production rates of 14.59-4.63 mL/day and lag phases of 10.72 19.7 days. Performance and kinetic parameters were obtained with the Gompertz equation and the first-order hydrolysis model with SY2 and SY3 diluted 25 % and SY1 50 %. A SY2 25 % gave a 17 % of TCOD conversion to methane as well as shorter lag phase (<1 day). Average estimated hydrolysis constant for SY was 0.0141 (+/ 0.003) day(-1), and SY2 25 % was more appropriate for faster methane production. Methane capture and biogas composition were dependent upon the SY source, and co digestion (or dilution) can be advantageous. PMID- 27276936 TI - A novel amidase from Brevibacterium epidermidis ZJB-07021: gene cloning, refolding and application in butyrylhydroxamic acid synthesis. AB - A novel amidase gene (bami) was cloned from Brevibacterium epidermidis ZJB-07021 by combination of degenerate PCR and high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). The deduced amino acid sequence showed low identity (<=55 %) with other reported amidases. The bami gene was overexpressed in Escherichia coli, and the resultant inclusion bodies were refolded and purified to homogeneity with a recovery of 22.6 %. Bami exhibited a broad substrate spectrum towards aliphatic, aromatic and heterocyclic amides, and showed the highest acyl transfer activity towards butyramide with specific activity of 1331.0 +/- 24.0 U mg(-1). Kinetic analysis demonstrated that purified Bami exhibited high catalytic efficiency (414.9 mM(-1) s(-1)) for acyl transfer of butyramide, with turnover number (K cat) of 3569.0 s(-1). Key parameters including pH, substrate/co-substrate concentration, reaction temperature and catalyst loading were investigated and the Bami showed maximum acyl transfer activity at 50 degrees C, pH 7.5. Enzymatic catalysis of 200 mM butyramide with 15 MUg mL(-1) purified Bami was completed in 15 min with a BHA yield of 88.1 % under optimized conditions. The results demonstrated the great potential of Bami for the production of a variety of hydroxamic acids. PMID- 27276938 TI - Communication: Proper treatment of classically forbidden electronic transitions significantly improves detailed balance in surface hopping. AB - Surface hopping is the most popular method for nonadiabatic molecular dynamics. Many have reported that it does not rigorously attain detailed balance at thermal equilibrium, but does so approximately. We show that convergence to the Boltzmann populations is significantly improved when the nuclear velocity is reversed after a classically forbidden hop. The proposed prescription significantly reduces the total number of classically forbidden hops encountered along a trajectory, suggesting that some randomization in nuclear velocity is needed when classically forbidden hops constitute a large fraction of attempted hops. Our results are verified computationally using two- and three-level quantum subsystems, coupled to a classical bath undergoing Langevin dynamics. PMID- 27276939 TI - Toward a W4-F12 approach: Can explicitly correlated and orbital-based ab initio CCSD(T) limits be reconciled? AB - In the context of high-accuracy computational thermochemistry, the valence coupled cluster with all singles and doubles (CCSD) correlation component of molecular atomization energies presents the most severe basis set convergence problem, followed by the (T) component. In the present paper, we make a detailed comparison, for an expanded version of the W4-11 thermochemistry benchmark, between, on the one hand, orbital-based CCSD/AV{5,6}Z + d and CCSD/ACV{5,6}Z extrapolation, and on the other hand CCSD-F12b calculations with cc-pVQZ-F12 and cc-pV5Z-F12 basis sets. This latter basis set, now available for H-He, B-Ne, and Al-Ar, is shown to be very close to the basis set limit. Apparent differences (which can reach 0.35 kcal/mol for systems like CCl4) between orbital-based and CCSD-F12b basis set limits disappear if basis sets with additional radial flexibility, such as ACV{5,6}Z, are used for the orbital calculation. Counterpoise calculations reveal that, while total atomization energies with V5Z F12 basis sets are nearly free of BSSE, orbital calculations have significant BSSE even with AV(6 + d)Z basis sets, leading to non-negligible differences between raw and counterpoise-corrected extrapolated limits. This latter problem is greatly reduced by switching to ACV{5,6}Z core-valence basis sets, or simply adding an additional zeta to just the valence orbitals. Previous reports that all electron approaches like HEAT (high-accuracy extrapolated ab-initio thermochemistry) lead to different CCSD(T) limits than "valence limit + CV correction" approaches like Feller-Peterson-Dixon and Weizmann-4 (W4) theory can be rationalized in terms of the greater radial flexibility of core-valence basis sets. For (T) corrections, conventional CCSD(T)/AV{Q,5}Z + d calculations are found to be superior to scaled or extrapolated CCSD(T)-F12b calculations of similar cost. For a W4-F12 protocol, we recommend obtaining the Hartree-Fock and valence CCSD components from CCSD-F12b/cc-pV{Q,5}Z-F12 calculations, but the (T) component from conventional CCSD(T)/aug'-cc-pV{Q,5}Z + d calculations using Schwenke's extrapolation; post-CCSD(T), core-valence, and relativistic corrections are to be obtained as in the original W4 theory. W4-F12 is found to agree slightly better than W4 with ATcT (active thermochemical tables) data, at a substantial saving in computation time and especially I/O overhead. A W4-F12 calculation on benzene is presented as a proof of concept. PMID- 27276940 TI - Generalized quantum Fokker-Planck equation for photoinduced nonequilibrium processes with positive definiteness condition. AB - This work provides a detailed derivation of a generalized quantum Fokker-Planck equation (GQFPE) appropriate for photo-induced quantum dynamical processes. The path integral method pioneered by Caldeira and Leggett (CL) [Physica A 121, 587 (1983)] is extended by utilizing a nonequilibrium influence functional applicable to different baths for the ground and the excited electronic states. Both nonequilibrium and non-Markovian effects are accounted for consistently by expanding the paths in the exponents of the influence functional up to the second order with respect to time. This procedure results in approximations involving only single time integrations for the exponents of the influence functional but with additional time dependent boundary terms that have been ignored in previous works. The boundary terms complicate the derivation of a time evolution equation but do not affect position dependent physical observables or the dynamics in the steady state limit. For an effective density operator with the boundary terms factored out, a time evolution equation is derived, through short time expansion of the effective action and Gaussian integration in analytically continued complex domain of space. This leads to a compact form of the GQFPE with time dependent kernels and additional terms, which renders the resulting equation to be in the Dekker form [Phys. Rep. 80, 1 (1981)]. Major terms of the equation are analyzed for the case of Ohmic spectral density with Drude cutoff, which shows that the new GQFPE satisfies the positive definiteness condition in medium to high temperature limit. Steady state limit of the GQFPE is shown to approach the well-known expression derived by CL in the high temperature and Markovian bath limit and also provides additional corrections due to quantum and non-Markovian effects of the bath. PMID- 27276941 TI - Anharmonic densities of states: A general dynamics-based solution. AB - Density of states is a fundamental physical characteristic that lies at the foundation of statistical mechanics and theoretical constructs that derive from them (e.g., kinetic rate theories, phase diagrams, and others). Even though most real physical systems are anharmonic, the vibrational density of states is customarily treated within the harmonic approximation, or with some partial, often limited, account for anharmonicity. The reason for this is that the problem of anharmonic densities of states stubbornly resisted a general and exact, yet convenient and straightforward in applications, solution. Here we formulate such a solution within both classical and quantum mechanics. It is based on actual dynamical behavior of systems as a function of energy and as observed, or monitored, on a chosen time scale, short or long. As a consequence, the resulting anharmonic densities of states are fully dynamically informed and, in general, time-dependent. As such, they lay the ground for formulation of new statistical mechanical frameworks that incorporate time and are ergodic, by construction, with respect to actual dynamical behavior of systems. PMID- 27276942 TI - J-factors of short DNA molecules. AB - The propensity of short DNA sequences to convert to the circular form is studied by a mesoscopic Hamiltonian method which incorporates both the bending of the molecule axis and the intrinsic twist of the DNA strands. The base pair fluctuations with respect to the helix diameter are treated as path trajectories in the imaginary time path integral formalism. The partition function for the sub ensemble of closed molecules is computed by imposing chain end boundary conditions both on the radial fluctuations and on the angular degrees of freedom. The cyclization probability, the J-factor, proves to be highly sensitive to the stacking potential, mostly to its nonlinear parameters. We find that the J-factor generally decreases by reducing the sequence length (N) and, more significantly, below N = 100 base pairs. However, even for very small molecules, the J-factors remain sizeable in line with recent experimental indications. Large bending angles between adjacent base pairs and anharmonic stacking appear as the causes of the helix flexibility at short length scales. PMID- 27276944 TI - Quantum dynamics of a vibronically coupled linear chain using a surrogate Hamiltonian approach. AB - Vibronic coupling between the electronic and vibrational degrees of freedom has been reported to play an important role in charge and exciton transport in organic photovoltaic materials, molecular aggregates, and light-harvesting complexes. Explicitly accounting for effective vibrational modes rather than treating them as a thermal environment has been shown to be crucial to describe the effect of vibronic coupling. We present a methodology to study dissipative quantum dynamics of vibronically coupled systems based on a surrogate Hamiltonian approach, which is in principle not limited by Markov approximation or weak system-bath interaction, using a vibronic basis. We apply vibronic surrogate Hamiltonian method to a linear chain system and discuss how different types of relaxation process, intramolecular vibrational relaxation and intermolecular vibronic relaxation, influence population dynamics of dissipative vibronic systems. PMID- 27276945 TI - An efficient and numerically stable procedure for generating sextic force fields in normal mode coordinates. AB - In this paper, we outline a general, scalable, and black-box approach for calculating high-order strongly coupled force fields in rectilinear normal mode coordinates, based upon constructing low order expansions in curvilinear coordinates with naturally limited mode-mode coupling, and then transforming between coordinate sets analytically. The optimal balance between accuracy and efficiency is achieved by transforming from 3 mode representation quartic force fields in curvilinear normal mode coordinates to 4 mode representation sextic force fields in rectilinear normal modes. Using this reduced mode-representation strategy introduces an error of only 1 cm(-1) in fundamental frequencies, on average, across a sizable test set of molecules. We demonstrate that if it is feasible to generate an initial semi-quartic force field in curvilinear normal mode coordinates from ab initio data, then the subsequent coordinate transformation procedure will be relatively fast with modest memory demands. This procedure facilitates solving the nuclear vibrational problem, as all required integrals can be evaluated analytically. Our coordinate transformation code is implemented within the extensible PyPES library program package, at http://sourceforge.net/projects/pypes-lib-ext/. PMID- 27276943 TI - Extracting water and ion distributions from solution x-ray scattering experiments. AB - Small-angle X-ray scattering measurements can provide valuable information about the solvent environment around biomolecules, but it can be difficult to extract solvent-specific information from observed intensity profiles. Intensities are proportional to the square of scattering amplitudes, which are complex quantities. Amplitudes in the forward direction are real, and the contribution from a solute of known structure (and from the waters it excludes) can be estimated from theory; hence, the amplitude arising from the solvent environment can be computed by difference. We have found that this "square root subtraction scheme" can be extended to non-zero q values, out to 0.1 A(-1) for the systems considered here, since the phases arising from the solute and from the water environment are nearly identical in this angle range. This allows us to extract aspects of the water and ion distributions (beyond their total numbers), by combining experimental data for the complete system with calculations for the solutes. We use this approach to test molecular dynamics and integral-equation (3D-RISM (three-dimensional reference interaction site model)) models for solvent structure around myoglobin, lysozyme, and a 25 base-pair duplex DNA. Comparisons can be made both in Fourier space and in terms of the distribution of interatomic distances in real space. Generally, computed solvent distributions arising from the MD simulations fit experimental data better than those from 3D-RISM, even though the total small-angle X-ray scattering patterns are very similar; this illustrates the potential power of this sort of analysis to guide the development of computational models. PMID- 27276946 TI - Geometry optimization made simple with translation and rotation coordinates. AB - The effective description of molecular geometry is important for theoretical studies of intermolecular interactions. Here we introduce a new translation rotation-internal coordinate (TRIC) system which explicitly includes the collective translations and rotations of molecules, or parts of molecules such as monomers or ligands, as degrees of freedom. The translations are described as the centroid position and the orientations are represented with the exponential map parameterization of quaternions. When TRIC is incorporated into geometry optimization calculations, the performance is consistently superior to existing coordinate systems for a diverse set of systems including water clusters, organic semiconductor donor-acceptor complexes, and small proteins, all of which are characterized by nontrivial intermolecular interactions. The method also introduces a new way to scan the molecular orientations while allowing orthogonal degrees of freedom to relax. Our findings indicate that an explicit description of molecular translation and rotation is a natural way to traverse the many dimensional potential energy surface. PMID- 27276947 TI - Magnetoelectroluminescence in organic light-emitting diodes. AB - The magnetoelectroluminescence of conjugated organic polymer films is widely accepted to arise from a polaron pair mechanism, but their magnetoconductance is less well understood. Here we derive a new relationship between the experimentally measurable magnetoelectroluminescence and magnetoconductance and the theoretically calculable singlet yield of the polaron pair recombination reaction. This relationship is expected to be valid regardless of the mechanism of the magnetoconductance, provided the mobilities of the free polarons are independent of the applied magnetic field (i.e., provided one discounts the possibility of spin-dependent transport). We also discuss the semiclassical calculation of the singlet yield of the polaron pair recombination reaction for materials such as poly(2,5-dioctyloxy-paraphenylene vinylene) (DOO-PPV), the hyperfine fields in the polarons of which can be extracted from light-induced electron spin resonance measurements. The resulting theory is shown to give good agreement with experimental data for both normal (H-) and deuterated (D-) DOO-PPV over a wide range of magnetic field strengths once singlet-triplet dephasing is taken into account. Without this effect, which has not been included in any previous simulation of magnetoelectroluminescence, it is not possible to reproduce the experimental data for both isotopologues in a consistent fashion. Our results also indicate that the magnetoconductance of DOO-PPV cannot be solely due to the effect of the magnetic field on the dissociation of polaron pairs. PMID- 27276948 TI - omegaB97M-V: A combinatorially optimized, range-separated hybrid, meta-GGA density functional with VV10 nonlocal correlation. AB - A combinatorially optimized, range-separated hybrid, meta-GGA density functional with VV10 nonlocal correlation is presented. The final 12-parameter functional form is selected from approximately 10 * 10(9) candidate fits that are trained on a training set of 870 data points and tested on a primary test set of 2964 data points. The resulting density functional, omegaB97M-V, is further tested for transferability on a secondary test set of 1152 data points. For comparison, omegaB97M-V is benchmarked against 11 leading density functionals including M06 2X, omegaB97X-D, M08-HX, M11, omegaM05-D, omegaB97X-V, and MN15. Encouragingly, the overall performance of omegaB97M-V on nearly 5000 data points clearly surpasses that of all of the tested density functionals. In order to facilitate the use of omegaB97M-V, its basis set dependence and integration grid sensitivity are thoroughly assessed, and recommendations that take into account both efficiency and accuracy are provided. PMID- 27276949 TI - Angular and internal state distributions of H2 (+) generated by (2 + 1) resonance enhanced multiphoton ionization of H2 using time-of-flight mass spectrometry. AB - We report direct measurement of the anisotropy parameter beta for the angular distribution of the photoelectron and photoion in (2 + 1) resonance enhanced multiphoton ionization process of H2 X (1)Sigmag (+) (v = 0, J = 0) molecules through the intermediate H2 E,F (1)Sigmag (+) (v' = 0, J' = 0) level (lambda = 201.684 nm) using a time-of-flight mass spectrometer. The time-of-flight spectra were recorded as the direction of polarization of the ionizing laser was varied with respect to the flight axis of the H2 molecular beam and were fitted to an angular distribution in an appropriately rotated coordinate system with the z axis oriented along the time-of-flight axis. The anisotropy parameter beta was found to be 1.72 +/- 0.13 by fitting the time-of-flight spectra and agreed with previous measurements. Using secondary ionization with a delayed laser pulse of different wavelength, we also determined the vibrational energy distribution of the ions, showing that 98% +/- 4% of the ions are generated in their ground vibrational state, in agreement with the calculated Franck-Condon factors between the H2 E,F (1)Sigmag (+) (v' = 0) and H2 (+) X (1)Sigmag (+) (v") vibrational levels. PMID- 27276950 TI - Absolute molecular transition frequencies measured by three cavity-enhanced spectroscopy techniques. AB - Absolute frequencies of unperturbed (12)C(16)O transitions from the near-infrared (3-0) band were measured with uncertainties five-fold lower than previously available data. The frequency axis of spectra was linked to the primary frequency standard. Three different cavity enhanced absorption and dispersion spectroscopic methods and various approaches to data analysis were used to estimate potential systematic instrumental errors. Except for a well established frequency stabilized cavity ring-down spectroscopy, we applied the cavity mode-width spectroscopy and the one-dimensional cavity mode-dispersion spectroscopy for measurement of absorption and dispersion spectra, respectively. We demonstrated the highest quality of the dispersion line shape measured in optical spectroscopy so far. We obtained line positions of the Doppler-broadened R24 and R28 transitions with relative uncertainties at the level of 10(-10). The pressure shifting coefficients were measured and the influence of the line asymmetry on unperturbed line positions was analyzed. Our dispersion spectra are the first demonstration of molecular spectroscopy with both axes of the spectra directly linked to the primary frequency standard, which is particularly desirable for the future reference-grade measurements of molecular spectra. PMID- 27276951 TI - Single-site Lennard-Jones models via polynomial chaos surrogates of Monte Carlo molecular simulation. AB - In this work, two Polynomial Chaos (PC) surrogates were generated to reproduce Monte Carlo (MC) molecular simulation results of the canonical (single-phase) and the NVT-Gibbs (two-phase) ensembles for a system of normalized structureless Lennard-Jones (LJ) particles. The main advantage of such surrogates, once generated, is the capability of accurately computing the needed thermodynamic quantities in a few seconds, thus efficiently replacing the computationally expensive MC molecular simulations. Benefiting from the tremendous computational time reduction, the PC surrogates were used to conduct large-scale optimization in order to propose single-site LJ models for several simple molecules. Experimental data, a set of supercritical isotherms, and part of the two-phase envelope, of several pure components were used for tuning the LJ parameters (epsilon, sigma). Based on the conducted optimization, excellent fit was obtained for different noble gases (Ar, Kr, and Xe) and other small molecules (CH4, N2, and CO). On the other hand, due to the simplicity of the LJ model used, dramatic deviations between simulation and experimental data were observed, especially in the two-phase region, for more complex molecules such as CO2 and C2 H6. PMID- 27276952 TI - Reflection and extinction of light by self-assembled monolayers of a quinque thiophene derivative: A coherent scattering approach. AB - Scattering matrix theory is used to describe resonant optical properties of molecular monolayers. Three types of coupling are included: exciton-exciton, exciton-photon, and exciton-phonon coupling. We use the K-matrix formalism, developed originally to describe neutron scattering spectra in nuclear physics to compute the scattering of polaritons by phonons. This perturbation approach takes into account the three couplings and allows one to go beyond molecular exciton theory without the need of introducing additional boundary conditions for the polariton. We demonstrate that reflection, absorption, and extinction of light by 2D self-assembled monolayers of molecules containing quinque-thiophene chromophoric groups can be calculated. The extracted coherence length of the Frenkel exciton is discussed. PMID- 27276953 TI - State-to-state mode selectivity in the HD + OH reaction: Perspectives from two product channels. AB - The state-to-state quantum dynamics (Jtot = 0) of the HD + OH(upsilon2 = 0, 1) reaction is studied using a reactant coordinate based method, which allows the analysis of both the H + DOH and D + HOH channels with a single propagation. The stretching vibration of the newly formed bond, namely, the OD bond in DOH and one OH bond in HOH, is excited, thanks to its strong coupling with the reaction coordinate at the transition state. On the other hand, the vibrational energy deposited into the OH reactant (upsilon2 = 1) is sequestered during the reaction in the spectator OH mode. The combined effect leads to the excitation of both the OD and OH stretching modes in the DOH product, and the dominance of the (002) normal-mode state population in the HOH product, which in the local-mode picture corresponds to the excitation of both OH bonds with one quantum each. The energy flow in this prototypical tetratomic reaction can be understood in terms of the sudden vector projection model. PMID- 27276954 TI - Reactions of substituted benzene anions with N and O atoms: Chemistry in Titan's upper atmosphere and the interstellar medium. AB - The likely existence of aromatic anions in many important extraterrestrial environments, from the atmosphere of Titan to the interstellar medium (ISM), is attracting increasing attention. Nitrogen and oxygen atoms are also widely observed in the ISM and in the ionospheres of planets and moons. In the current work, we extend previous studies to explore the reactivity of prototypical aromatic anions (deprotonated toluene, aniline, and phenol) with N and O atoms both experimentally and computationally. The benzyl and anilinide anions both exhibit slow associative electron detachment (AED) processes with N atom, and moderate reactivity with O atom in which AED dominates but ionic products are also formed. The reactivity of phenoxide is dramatically different; there is no measurable reaction with N atom, and the moderate reactivity with O atom produces almost exclusively ionic products. The reaction mechanisms are studied theoretically by employing density functional theory calculations, and spin conversion is found to be critical for understanding some product distributions. This work provides insight into the rich gas-phase chemistry of aromatic ion-atom reactions and their relevance to ionospheric and interstellar chemistry. PMID- 27276955 TI - Quantum chemical study of the geometrical and electronic structures of ScSi3 ( /0) clusters and assignment of the anion photoelectron spectra. AB - The geometrical and electronic structures of ScSi3 (-/0) clusters have been studied with the B3LYP, CCSD(T), and CASPT2 methods. The ground state of the anionic cluster was evaluated to be the (1)A1 of rhombic eta(2)-(Si3)Sc(-) isomer, whereas that of the neutral cluster was computed to be the (2)A1 of the same isomer. All features in the 266 and 193 nm photoelectron spectra of ScSi3 ( ) cluster were interpreted by the one- and two-electron detachments from the (1)A1 of rhombic eta(2)-(Si3)Sc(-) isomer. The Franck-Condon factor simulation results show that the first broad band starting at 1.78 eV in the spectra comprises several vibrational progression peaks of two totally symmetric modes with the corresponding frequencies of 296 and 354 cm(-1). PMID- 27276956 TI - The bond length and bond energy of gaseous CrW. AB - Supersonically cooled CrW was studied using resonant two-photon ionization spectroscopy. The vibronically resolved spectrum was recorded over the region 21 100 to 23 400 cm(-1), showing a very large number of bands. Seventeen of these bands, across three different isotopologues, were rotationally resolved and analyzed. All were found to arise from the ground (1)Sigma(+) state of the molecule and to terminate on states with Omega' = 0. The average r0 bond length across the three isotopic forms was determined to be 1.8814(4) A. A predissociation threshold was observed in this dense manifold of vibronic states at 23 127(10) cm(-1), indicating a bond dissociation energy of D0(CrW) = 2.867(1) eV. Using the multiple bonding radius determined for atomic Cr in previous work, the multiple bonding radius for tungsten was calculated to be 1.037 A. Comparisons are made between CrW and the previously investigated group 6 diatomic metals, Cr2, CrMo, and Mo2, and to previous computational studies of this molecule. It is also found that the accurately known bond dissociation energies of group 5/6 metal diatomics Cr2, V2, CrW, NbCr, VNb, Mo2, and Nb2 display a qualitative linear dependence on the sum of the d-orbital radial expectation values, r; this relationship allows the bond dissociation energies of other molecules of this type to be estimated. PMID- 27276957 TI - Evidence for a liquid-liquid critical point in supercooled water within the E3B3 model and a possible interpretation of the kink in the homogeneous nucleation line. AB - Supercooled water exhibits many thermodynamic anomalies, and several scenarios have been proposed to interpret them, among which the liquid-liquid critical point (LLCP) hypothesis is the most commonly discussed. We investigated Widom lines and the LLCP of deeply supercooled water, by using molecular dynamics simulation with a newly reparameterized water model that explicitly includes three-body interactions. Seven isobars are studied from ambient pressure to 2.5 kbar, and Widom lines are identified by calculating maxima in the coefficient of thermal expansion and the isothermal compressibility (both with respect to temperature). From these data we estimate that the LLCP of the new water model is at 180 K and 2.1 kbar. The oxygen radial distribution function is calculated along the 2 kbar isobar. It shows a steep change in the height of its second peak between 180 and 185 K, which indicates a transition between the high-density liquid and low-density liquid phases and which is consistent with the ascribed location of the critical point. The good agreement of the height of the second peak of the radial distribution function between simulation and experiment at 1 bar, as a function of temperature, supports the validity of the model. The location of the LLCP within the model is close to the kink in the experimental homogeneous nucleation line. We use existing experimental data to argue that the experimental LLCP is at 168 K and 1.95 kbar and speculate how this LLCP and its Widom line might be responsible for the kink in the homogeneous nucleation line. PMID- 27276958 TI - Separating the effects of repulsive and attractive forces on the phase diagram, interfacial, and critical properties of simple fluids. AB - Molecular simulations in the canonical and isothermal-isobaric ensembles were performed to study the effect of varying the shape of the intermolecular potential on the phase diagram, critical, and interfacial properties of model fluids. The molecular interactions were modeled by the Approximate Non-Conformal (ANC) theory potentials. Unlike the Lennard-Jones or Morse potentials, the ANC interactions incorporate parameters (called softnesses) that modulate the steepness of the potential in their repulsive and attractive parts independently. This feature allowed us to separate unambiguously the role of each region of the potential on setting the thermophysical properties. In particular, we found positive linear correlation between all critical coordinates and the attractive and repulsive softness, except for the critical density and the attractive softness which are negatively correlated. Moreover, we found that the physical properties related to phase coexistence (such as span of the liquid phase between the critical and triple points, variations in the P-T vaporization curve, interface width, and surface tension) are more sensitive to changes in the attractive softness than to the repulsive one. Understanding the different roles of attractive and repulsive forces on phase coexistence may contribute to developing more accurate models of liquids and their mixtures. PMID- 27276959 TI - Chemical potential and entropy in monodisperse and polydisperse hard-sphere fluids using Widom's particle insertion method and a pore size distribution-based insertion probability. AB - We estimate the excess chemical potential DeltaMU and excess entropy per particle Deltas of computer-generated, monodisperse and polydisperse, frictionless hard sphere fluids. For this purpose, we utilize the Widom particle insertion method, which for hard-sphere systems relates DeltaMU to the probability to successfully (without intersections) insert a particle into a system. This insertion probability is evaluated directly for each configuration of hard spheres by extrapolating to infinity the pore radii (nearest-surface) distribution and integrating its tail. The estimates of DeltaMU and Deltas are compared to (and comply well with) predictions from the Boublik-Mansoori-Carnahan-Starling-Leland equation of state. For polydisperse spheres, we employ log-normal particle radii distributions with polydispersities delta = 0.1, 0.2, and 0.3. PMID- 27276960 TI - Hydrogen bonding and orientation effects on the accommodation of methylamine at the air-water interface. AB - Methylamine is an abundant amine compound detected in the atmosphere which can affect the nature of atmospheric aerosol surfaces, changing their chemical and optical properties. Molecular dynamics simulation results show that methylamine accommodation on water is close to unity with the hydrophilic head group solvated in the interfacial environment and the methyl group pointing into the air phase. A detailed analysis of the hydrogen bond network indicates stronger hydrogen bonds between water and the primary amine group at the interface, suggesting that atmospheric trace gases will likely react with the methyl group instead of the solvated amine site. These findings suggest new chemical pathways for methylamine acting on atmospheric aerosols in which the methyl group is the site of orientation specific chemistry involving its conversion into a carbonyl site providing hydrophilic groups for uptake of additional water. This conversion may explain the tendency of aged organic aerosols to form cloud condensation nuclei. At the same time, formation of NH2 radical and formaldehyde is suggested to be a new source for NH2 radicals at aerosol surfaces, other than by reaction of absorbed NH3. The results have general implications for the chemistry of other amphiphilic organics, amines in particular, at the surface of atmospherically relevant aerosols. PMID- 27276961 TI - Comparison of three empirical force fields for phonon calculations in CdSe quantum dots. AB - Three empirical interatomic force fields are parametrized using structural, elastic, and phonon dispersion data for bulk CdSe and their predictions are then compared for the structures and phonons of CdSe quantum dots having average diameters of ~2.8 and ~5.2 nm (~410 and ~2630 atoms, respectively). The three force fields include one that contains only two-body interactions (Lennard-Jones plus Coulomb), a Tersoff-type force field that contains both two-body and three body interactions but no Coulombic terms, and a Stillinger-Weber type force field that contains Coulombic interactions plus two-body and three-body terms. While all three force fields predict nearly identical peak frequencies for the strongly Raman-active "longitudinal optical" phonon in the quantum dots, the predictions for the width of the Raman peak, the peak frequency and width of the infrared absorption peak, and the degree of disorder in the structure are very different. The three force fields also give very different predictions for the variation in phonon frequency with radial position (core versus surface). The Stillinger-Weber plus Coulomb type force field gives the best overall agreement with available experimental data. PMID- 27276962 TI - Lateral critical Casimir force in two-dimensional inhomogeneous Ising strip. Exact results. AB - We consider two-dimensional Ising strip bounded by two planar, inhomogeneous walls. The inhomogeneity of each wall is modeled by a magnetic field acting on surface spins. It is equal to +h1 except for a group of N1 neighboring surface spins where it is equal to -h1. The inhomogeneities of the upper and lower wall are shifted with respect to each other by a lateral distance L. Using exact diagonalization of the transfer matrix, we study both the lateral and normal critical Casimir forces as well as magnetization profiles for different temperature regimes: below the wetting temperature, between the wetting and the critical temperature, and above the critical temperature. The lateral critical Casimir force acts in the direction opposite to the shift L, and the excess normal force is always attractive. Upon increasing the shift L we observe, depending on the temperature regime, three different scenarios of breaking of the capillary bridge of negative magnetization connecting the inhomogeneities of the walls across the strip. As long as there exists a capillary bridge in the system, the magnitude of the excess total critical Casimir force is almost constant, with its direction depending on L. By investigating the bridge morphologies we have found a relation between the point at which the bridge breaks and the inflection point of the force. We provide a simple argument that some of the properties reported here should also hold for different models of the strip with the same type of inhomogeneity. PMID- 27276963 TI - Growth and stability of rocksalt Zn1-xMgxO epilayers and ZnO/MgO superlattice on MgO (100) substrate by molecular beam epitaxy. AB - Zn1-xMgxO films with x = 0.04-0.50 grown on MgO (100) substrates by molecular beam epitaxy retain the rocksalt (rs) crystal structure and grow epitaxially for x >= 0.17. In addition, the rs-ZnO epilayer is observed to be stable up to a thickness of 5 nm and also in a ZnO/MgO superlattice sample. However, a portion of the superlattice has transformed to wurtzite (wz)-structure islands in a self accommodated manner during growth. The transformation is a combination of a Bain distortion, an in-plane rotation of 14.5 degrees , and a Peierls distortion, resulting in an orientation relationship of (100)rs//(1010)wz and <011>rs ~//<1213>wz. In such a manner, the volume expansion is only necessary along the growth direction and the in-plane strains can be minimized. A negative pressure generated during the transformation of ZnO stabilizes the MgO into a wurtzite structure. PMID- 27276964 TI - Titratable macroions in multivalent electrolyte solutions: Strong coupling dressed ion approach. AB - We present a theoretical description of the effect of polyvalent ions on the interaction between titratable macroions. The model system consists of two point like macroions with dissociable sites, immersed in an asymmetric ionic mixture of monovalent and polyvalent salts. We formulate a dressed ion strong coupling theory, based on the decomposition of the asymmetric ionic mixture into a weakly electrostatically coupled monovalent salt and into polyvalent ions that are strongly electrostatically coupled to the titratable macro-ions. The charge of the macroions is not considered as fixed, but is allowed to respond to local bathing solution parameters (electrostatic potential, pH of the solution, and salt concentration) through a simple charge regulation model. The approach presented, yielding an effective polyvalent-ion mediated interaction between charge-regulated macroions at various solution conditions, describes the strong coupling equivalent of the Kirkwood-Schumaker interaction. PMID- 27276965 TI - Polymer extension under flow: A path integral evaluation of the free energy change using the Jarzynski relation. AB - The Jarzynski relation (and its variants) has provided a route to the experimental evaluation of equilibrium free energy changes based on measurements conducted under arbitrary non-equilibrium conditions. Schroeder and co-workers [Soft Matter 10, 2178 (2014) and J. Chem. Phys. 141, 174903 (2014)] have recently exploited this fact to determine the elastic properties of model DNA from simulations and experiments of chain extension under elongational flow, bypassing the need to make these measurements mechanically using sophisticated optical trapping techniques. In this paper, motivated by these observations, we investigate chain elasticity analytically, using the Jarzynski relation and a finitely extensible nonlinear elastic-type Rouse model within a path integral formalism to calculate (essentially exactly) both the flow-induced free energy change between chain conformations of definite average end-to-end distance, as well as the force-extension curve that follows from it. This curve, based on a new analytic expression, matches the trends in the corresponding curve obtained from a model of chain stretching developed by Marko and Siggia [Macromolecules 28, 8759 (1995)], which itself is in very satisfactory agreement with the numerical and experimental data from the work of Schroeder et al. PMID- 27276966 TI - Self-assembly and glass-formation in a lattice model of telechelic polymer melts: Influence of stiffness of the sticky bonds. AB - Telechelic polymers are chain macromolecules that may self-assemble through the association of their two mono-functional end groups (called "stickers"). A deep understanding of the relation between microscopic molecular details and the macroscopic physical properties of telechelic polymers is important in guiding the rational design of telechelic polymer materials with desired properties. The lattice cluster theory (LCT) for strongly interacting, self-assembling telechelic polymers provides a theoretical tool that enables establishing the connections between important microscopic molecular details of self-assembling polymers and their bulk thermodynamics. The original LCT for self-assembly of telechelic polymers considers a model of fully flexible linear chains [J. Dudowicz and K. F. Freed, J. Chem. Phys. 136, 064902 (2012)], while our recent work introduces a significant improvement to the LCT by including a description of chain semiflexibility for the bonds within each individual telechelic chain [W.-S. Xu and K. F. Freed, J. Chem. Phys. 143, 024901 (2015)], but the physically associative (or called "sticky") bonds between the ends of the telechelics are left as fully flexible. Motivated by the ubiquitous presence of steric constraints on the association of real telechelic polymers that impart an additional degree of bond stiffness (or rigidity), the present paper further extends the LCT to permit the sticky bonds to be semiflexible but to have a stiffness differing from that within each telechelic chain. An analytical expression for the Helmholtz free energy is provided for this model of linear telechelic polymer melts, and illustrative calculations demonstrate the significant influence of the stiffness of the sticky bonds on the self-assembly and thermodynamics of telechelic polymers. A brief discussion is also provided for the impact of self-assembly on glass-formation by combining the LCT description for this extended model of telechelic polymers with the Adam-Gibbs relation between the structural relaxation time and the configurational entropy. PMID- 27276967 TI - Highly efficient and selective pressure-assisted photon-induced polymerization of styrene. AB - The polymerization process of condensed styrene to produce polystyrene as an industrially important polymeric material was investigated using a novel approach by combining external compression with ultraviolet radiation. The reaction evolution was monitored as a function of time and the reaction products were characterized by in situ Fourier transform infrared spectroscopy. By optimizing the loading pressures, we observed highly efficient and selective production of polystyrene of different tacticities. Specifically, at relatively low loading pressures, infrared spectra suggest that styrene monomers transform to amorphous atactic polystyrene (APS) with minor crystalline isotactic polystyrene. In contrast, APS was found to be the sole product when polymerization occurs at relatively higher loading pressures. The time-dependent reaction profiles allow the examination of the polymerization kinetics by analyzing the rate constant and activation volume as a function of pressure. As a result, an optimized pressure condition, which allows a barrierless reaction to proceed, was identified and attributed to the very desirable reaction yield and kinetics. Finally, the photoinitiated reaction mechanism and the growth geometry of the polymer chains were investigated from the energy diagram of styrene and by the topology analysis of the crystal styrene. This study shows strong promise to produce functional polymeric materials in a highly efficient and controlled manner. PMID- 27276968 TI - Density-functional description of polymer crystals: A comparative study of recent van der Waals functionals. AB - Due to the lack of treatment of long-range dispersion energies, density functional theory with local and semilocal approximations of exchange-correlation energy is known to fail in describing van der Waals complexes, including polymer crystals. This limitation can be overcome by using a different class of functionals, called van der Waals density functional (vdW-DF), originally developed by Dion et al. [Phys. Rev. Lett. 92, 246401 (2004)]. In this work, we performed a systematic study of structural properties of polymeric crystals using the original vdW-DF functional by Dion et al. and its variants and refinements. Our study shows that this class of functional outperforms the conventional LDA or PBE functionals and gives results with similar accuracy to that of empirical dispersion-corrected schemes such as DFT-D. This study suggests the use of vdW DF2 functional - a revised version of vdW-DF functional - to obtain a high fidelity prediction of structural and other properties of polymeric materials. PMID- 27276969 TI - The influence of torsion on excimer formation in bipolar host materials for blue phosphorescent OLEDs. AB - We present a combined detailed spectroscopic and quantum chemical study on the bipolar host materials BPTRZ and MBPTRZ in solution and in neat film. In the two compounds, the hole transporting carbazole is separated from the electron transporting triazine moiety by a fully aromatic but non-conjugated meta-linked biphenyl unit. The two materials differ by an additional steric twist at the biphenyl in MBPTRZ, which is achieved by methyl-substitution in 2- and 2' position of the biphenyl. We find that while the twist shifts the triplet state in MBPTRZ to higher energies (3.0 eV in solution) compared to BPTRZ (2.8 eV in solution), this also localizes electron density on the carbazole moiety, leading to excimer formation in neat films. PMID- 27276971 TI - Bifurcation of transition paths induced by coupled bistable systems. AB - We discuss the transition paths in a coupled bistable system consisting of interacting multiple identical bistable motifs. We propose a simple model of coupled bistable gene circuits as an example and show that its transition paths are bifurcating. We then derive a criterion to predict the bifurcation of transition paths in a generalized coupled bistable system. We confirm the validity of the theory for the example system by numerical simulation. We also demonstrate in the example system that, if the steady states of individual gene circuits are not changed by the coupling, the bifurcation pattern is not dependent on the number of gene circuits. We further show that the transition rate exponentially decreases with the number of gene circuits when the transition path does not bifurcate, while a bifurcation facilitates the transition by lowering the quasi-potential energy barrier. PMID- 27276970 TI - Explicit-water theory for the salt-specific effects and Hofmeister series in protein solutions. AB - Effects of addition of salts on stability of aqueous protein solutions are studied theoretically and the results are compared with experimental data. In our approach, all the interacting species, proteins, ions, and water molecules, are accounted for explicitly. Water molecules are modeled as hard spheres with four off-center attractive square-well sites. These sites serve to bind either another water or to solvate the ions or protein charges. The ions are represented as charged hard spheres, and decorated by attractive sites to allow solvation. Spherical proteins simultaneously possess positive and negative groups, represented by charged hard spheres, attached to the surface of the protein. The attractive square-well sites, mimicking the protein-protein van der Waals interaction, are located on the surface of the protein. To obtain numerical results, we utilized the energy route of Wertheim's associative mean spherical approximation. From measurable properties, we choose to calculate the second virial coefficient B2, which is closely related to the tendency of proteins to aggregate and eventually crystalize. Calculations are in agreement with experimental trends: (i) For low concentration of added salt, the alkali halide salts follow the inverse Hofmeister series. (ii) At higher concentration of added salt, the trend is reversed. (iii) When cations are varied, the salts follow the direct Hofmeister series. (iv) In contrast to the colloidal theories, our approach correctly predicts the non-monotonic behavior of B2 upon addition of salts. (v) With respect to anions, the theory predicts for the B2 values to follow different sequences below and above the iso-ionic point, as also confirmed experimentally. (vi) A semi-quantitative agreement between measured and calculated values for the second virial coefficient, as functions of pH of solution and added salt type and concentration, is obtained. PMID- 27276972 TI - Erratum: "Dissociative adsorption of H2O on LiCoO2 (00l) surfaces: Co reduction induced by electron transfer from intrinsic defects" [J. Chem. Phys. 144, 184706 (2016)]. PMID- 27276973 TI - Erratum: "Linear-scaling time-dependent density-functional theory beyond the Tamm Dancoff approximation: Obtaining efficiency and accuracy with in situ optimised local orbitals" [J. Chem. Phys. 143, 204107 (2015)]. PMID- 27276974 TI - Erratum: "A search for manifestation of two types of collective excitations in dynamic structure of a liquid metal: Ab initio study of collective excitations in liquid Na" [J. Chem. Phys. 144, 194501 (2016)]. PMID- 27276975 TI - Characterization of the nuclear import signal of herpes simplex virus 1 UL31. AB - The herpes simplex virus 1 (HSV-1) UL31 protein is a multifunctional nucleoprotein that is important for viral infection; however, little is known concerning its subcellular localization signal. Here, by transfection with a series of HSV-1 UL31 deletion mutants fused to enhanced yellow fluorescent protein (EYFP), a bipartite nuclear localization signal (NLS) was identified and mapped to amino acids (aa) 1 to 27 (MYDTDPHRRGSRPGPYHGKERRRSRSS). Additionally, fluorescence results showed that the predicted nuclear export signal (NES) might be nonfunctional, and the functional NES of UL31 might require a specific conformation. Taken together, these results would provide significant information for the study of the biological function of UL31 during HSV-1 infection. PMID- 27276976 TI - Intraspecific differences in cadmium tolerance of Nitzschia palea (Kutzing) W. Smith: a biochemical approach. AB - Intraspecific variability occurs in all types of organisms and is a driving force to speciation, conferring genotypic and phenotypic differences that enable adaptive responses to sub-lethal stimuli such as exposure to pollutants (including cadmium, Cd). Thus, differences in biochemical parameters are expected among isolates of the same species. Studying the extent of these differences throughout a stress range, will provide information for the development of approaches to mitigate habitat contamination. This work was designed to identify possible differences in Cd tolerance of five isolates of the freshwater diatom Nitzschia palea from different sampling sites. Each isolate was exposed to five increasing Cd concentrations during 10 days. Growth inhibition was assessed and intracellular accumulation of Cd was quantified. Superoxide dismutase and catalase activities were determined. Glutathione as well as lipid peroxidation (LPO) and intracellular protein content were quantified. The results obtained identified intraspecific differences among isolates. These differences were associated with different approaches of coping with Cd stress. Higher intracellular Cd concentrations induced lower tolerance in isolates, since antioxidant mechanisms were unable to fight effectively against higher oxidative stress. Reversely, lower intracellular accumulation of Cd induced lower oxidative damage and allowed cells to better tolerate exposure to Cd. LPO emerged as an excellent marker of oxidative stress in N. palea and its use can differentiate isolates according to their tolerance. PMID- 27276977 TI - Is it time for airway management education to be mandatory? PMID- 27276979 TI - Detailed analysis of B-mode ultrasonograms: backward-looking ultrasound diagnosis or source of inspiration? PMID- 27276978 TI - Genetic and Environmental Influences on Literacy and Numeracy Performance in Australian School Children in Grades 3, 5, 7, and 9. AB - We examined the extent to which genes and the environment contributed to variation in and covariation among reading, spelling, grammar and punctuation, writing, and numeracy in Australian school children in Grades 3, 5, 7, and 9. Heritability was generally high: reading .58-.71 (excepting Grade 5 girls), spelling .68-.78; grammar and punctuation .52-.66, writing .39-.52, and numeracy .39-.79. Boys' performance varied more than girls in spelling and numeracy, and the common environment was a greater influence in girls than boys in Grade 3 numeracy and Grade 5 reading. Independent pathway models showed similar genetic and environmental structures at each grade with approximately one third to one half of the variation in each domain due to genes that influenced all domains. The covariation among the domains was largely mediated by genes. Results suggest substantial uniformity in the environmental factors influencing these academic domains. PMID- 27276980 TI - A basic study on sonoporation with microbubbles exposed to pulsed ultrasound. AB - PURPOSE: Sonoporation is an ultrasound technique that enables large molecules that normally do not penetrate the cell membrane to pass through it. Recent studies show that pulsed ultrasound in the presence of microbubbles increases the permeability of the cell membrane. However, the mechanism and basic properties of this sonoporation remain unclear. We thus investigated the mechanism of generation and frequency of occurrence of sonoporation, as well as the repair of a cell membrane damaged by microbubbles. METHODS: The spatial relationship between microbubbles and cells was observed microscopically when cells were sonicated with pulsed ultrasound. Effects of microbubbles on the cells were observed with a high-speed camera, and the ratio of cell membrane damage and repair was examined using fluorescent microscopy. RESULTS: Damage to the cell membrane, caused mainly by mechanical effects of the expansion and contraction of microbubbles, significantly increased the permeability of the cell membrane. The frequency of cell membrane damage was closely associated with the presence of microbubbles and increased with increase in acoustic pressure. The ratio of repair of damaged cells was about 70% during 3 min after a single shot of pulsed ultrasound, indicating that repair of damaged cell membranes requires little time. CONCLUSION: We examined the frequency of occurrence of cell membrane damage and repair in sonoporation using pulsed ultrasound and microbubbles. Our results should prove useful for improving pulsed-ultrasound sonoporation. PMID- 27276981 TI - Evaluation of intratumoral hemodynamics with color Doppler imaging in patients with colorectal carcinoma: comparison between waveform analysis and histopathologic characteristics. AB - PURPOSE: We studied the relation between intratumoral hemodynamics and histopathologic characteristics in patients with colorectal carcinoma. METHODS: A series of 82 patients with 28 well-differentiated adenocarcinomas, 40 moderately differentiated adenocarcinomas, 10 poorly differentiated adenocarcinomas, and 4 mucinous adenocarcinomas underwent color Doppler examination and surgical treatment. The waveform of blood flow in the thickened wall of the colon was analyzed by determining the maximum velocity (Vmax) and resistance index (RI). These parameters were compared with histopathologic findings of the resected specimens: gross form, tumor size, depth of invasion, histologic stage, and histopathologic classification. RESULTS: Both Vmax and RI were higher in the invasive tumors rather than the expansive ones. Vmax and tumor size were not correlated; however, the RI increased proportionately with tumor size in tumors larger than 4 cm in diameter. Both parameters increased with depth of invasion and histologic stage through stage IIIb. Both were markedly higher in mucinous adenocarcinomas than in the other histopathologic types. Furthermore, Vmax in well, moderately, and poorly differentiated adenocarcinomas did not differ significantly, although RI was negatively associated with the degree of differentiation. CONCLUSIONS: We concluded that blood-flow analysis is closely associated with histopathologic findings of colorectal carcinomas and that it provides information useful in the clinical management of these patients. PMID- 27276982 TI - Vascularity of gastric carcinoma: evaluation using color Doppler ultrasonography. AB - PURPOSE: The purpose of this study was to investigate the vascularity of primary gastric cancer lesions using color Doppler ultrasonography. METHODS: We used color Doppler ultrasonography to study 78 patients with gastric cancer detected on B-mode ultrasonographic examination and 14 patients without gastric tumors but with a slightly thickened gastric wall that was also detected on B-mode ultrasound. The color Doppler signals of the gastric lesions were graded as (-), no color signals; (+), slight increase in number of color signals; and (++), an obvious increase in number of color signals. The vessel area outside the tumor area in the microscopic pathological specimens was also calculated. RESULTS: The color signals of 13 (18%) of the 71 gastric cancer patients were graded (-); those of 14 (20%) patients were graded (+); and those of 44 (62%) patients were graded (++). The color signals for 9 (65%) of 14 patients without gastric tumors were graded (-); those of 4 (28%) patients were graded (+), and those of 1 patient (7%) were graded (++). These differences were significant (P = 0.0002). The vessel count ratio in the microscopic pathologic specimens was also significantly higher in patients with an increased number of color signals than in those without an increased number of color signals (P = 0.002). CONCLUSION: Color Doppler ultrasound showed increased vascularity in the gastric cancers in most of the subjects (82%, 58/71). Furthermore, color Doppler ultrasound also showed no increase in vascularity in most subjects (65%, 9/14) whose B-mode ultrasonograms showed thickened gastric walls but who did not have gastric cancer. Thus, color Doppler imaging may prove useful as a screening modality for gastric cancer. PMID- 27276983 TI - Primary left atrial tumor showing mitral valve stenosis and left upper lobe pulmonary edema: report of a case. AB - Myxoma and other neoplasms in the left atrium often show signs and symptoms similar to those of mitral valve stenosis. Malignant fibrous histiocytoma, one of the most common sarcomas, occurs in the deep soft tissue of the limbs and retroperitoneum in adults. With the exception of primary lung cancer, however, sarcomatous intravascular extension in the lung and infiltration into the left atrium are rare. We report a case of overt left upper lobe pulmonary edema observed on chest radiograms and a mass occupying much of the left atrium and exhibiting hemodynamics similar to those of mitral valve stenosis on transthoracic echocardiography. Intraoperative and pathologic examination showed the mass to be a primary malignant fibrous histiocytoma extending from the left upper pulmonary vein into the left atrium. PMID- 27276984 TI - Improved prediction of antibody VL-VH orientation. AB - Antibodies are important immune molecules with high commercial value and therapeutic interest because of their ability to bind diverse antigens. Computational prediction of antibody structure can quickly reveal valuable information about the nature of these antigen-binding interactions, but only if the models are of sufficient quality. To achieve high model quality during complementarity-determining region (CDR) structural prediction, one must account for the VL-VH orientation. We developed a novel four-metric VL-VH orientation coordinate frame. Additionally, we extended the CDR grafting protocol in RosettaAntibody with a new method that diversifies VL-VH orientation by using 10 VL-VH orientation templates rather than a single one. We tested the multiple template grafting protocol on two datasets of known antibody crystal structures. During the template-grafting phase, the new protocol improved the fraction of accurate VL-VH orientation predictions from only 26% (12/46) to 72% (33/46) of targets. After the full RosettaAntibody protocol, including CDR H3 remodeling and VL-VH re-orientation, the new protocol produced more candidate structures with accurate VL-VH orientation than the standard protocol in 43/46 targets (93%). The improved ability to predict VL-VH orientation will bolster predictions of other parts of the paratope, including the conformation of CDR H3, a grand challenge of antibody homology modeling. PMID- 27276985 TI - Coagulopathy in fulminant liver failure with ultimately fatal clot formation. PMID- 27276987 TI - A giant epiglottic cyst. PMID- 27276986 TI - Community-acquired pneumonia related to intracellular pathogens. AB - Community-acquired pneumonia (CAP) is associated with high rates of morbidity and mortality worldwide; the annual incidence of CAP among adults in Europe has ranged from 1.5 to 1.7 per 1000 population. Intracellular bacteria are common causes of CAP. However, there is considerable variation in the reported incidence between countries and change over time. The intracellular pathogens that are well established as causes of pneumonia are Legionella pneumophila, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci, and Coxiella burnetii. Since it is known that antibiotic treatment for severe CAP is empiric and includes coverage of typical and atypical pathogens, microbiological diagnosis bears an important relationship to prognosis of pneumonia. Factors such as adequacy of initial antibiotic or early de-escalation of therapy are important variables associated with outcomes, especially in severe cases. Intracellular pathogens sometimes appear to cause more severe disease with respiratory failure and multisystem dysfunction associated with fatal outcomes. The clinical relevance of intracellular pathogens in severe CAP has not been specifically investigated. We review the prevalence, general characteristics, and outcomes of severe CAP cases caused by intracellular pathogens. PMID- 27276988 TI - Desperate times call for desperate measures: benefits and costs of toxin antitoxin systems. AB - Toxin-antitoxin (TA) loci were first described as killing systems for plasmid maintenance. The surprisingly abundant presence of TA loci in bacterial chromosomes has stimulated an extensive research in the recent decade aimed to understand the biological importance of these potentially deadly systems. Accumulating evidence suggests that the evolutionary success of genomic TA systems could be explained by their ability to increase bacterial fitness under stress conditions. While TA systems remain quiescent under favorable growth conditions, the toxins can be activated in response to stress resulting in growth suppression and development of stress-tolerant dormant state. Yet, several studies suggest that the TA-mediated stress protection is costly and traded off against decreased fitness under normal growth conditions. Here, we give an overview of the fitness benefits of the chromosomal TA systems, and discuss the costs of TA-mediated stress protection. PMID- 27276989 TI - Facial palsy following cochlear implantation. AB - Owing to its anatomical location, the facial nerve (FN) is at risk of damage during cochlear implantation, especially during posterior tympanotomy. The aim of this study was, therefore, to evaluate the risk of FN palsy following cochlear implantation surgery via mastoidectomy and posterior tympanotomy approach (facial recess). This is a retrospective study. The data bank of patients who received a cochlear implant between 2000 and 2012 was analyzed. 3403 surgeries were done during this period. Records of the patients who had suffered from FN palsy were evaluated and the type of FN palsy, the severity, time of onset, and need for revision surgery were recorded. 0.76 % (26/3403) of the patients had FN palsy and were, therefore, included in the study. 76.9 % (20/26) subjects were 18 years or older. 0.15 % (5 subjects) suffered from immediate FN palsy and 0.62 % (21 subjects) from delayed FN palsy. Intraoperative FN injury was documented in only three subjects of the immediate FN palsy group. In two subjects with immediate FN palsy, the FN was intraoperatively exposed but not injured, despite these individuals' experiencing FN palsy. In 100 % of the immediate onset FN palsy group a part of the FN was exposed during surgery, whereas it was exposed only in 9.5 % of the delay onset FN palsy group. Although the FN was bone protected in 19 subjects, they had FN palsy. Most of the subjects presented House-Brackmann grade III or IV (69.2 %). All of the subjects were treated initially with a conservative therapy, only 42.3 % (11 subjects) underwent revision surgery. The recovery rate was 80.8 % (in immediate onset palsy 40 %, in delayed onset palsy 90.5 %). Cochlear implantation entails only a minimal risk of FN palsy and that FN palsy is chiefly a transient problem. PMID- 27276990 TI - A clinical assessment of cochlear implant recipient performance: implications for individualized map settings in specific environments. AB - Individual speech intelligibility was measured in quiet and noise for cochlear Implant recipients upgrading from the Freedom to the CP900 series sound processor. The postlingually deafened participants (n = 23) used either Nucleus CI24RE or CI512 cochlear implant, and currently wore a Freedom sound processor. A significant group mean improvement in speech intelligibility was found in quiet (Freiburg monosyllabic words at 50 dBSPL) and in noise (adaptive Oldenburger sentences in noise) for the two CP900 series SmartSound programs compared to the Freedom program. Further analysis was carried out on individual's speech intelligibility outcomes in quiet and in noise. Results showed a significant improvement or decrement for some recipients when upgrading to the new programs. To further increase speech intelligibility outcomes when upgrading, an enhanced upgrade procedure is proposed that includes additional testing with different signal-processing schemes. Implications of this research are that future automated scene analysis and switching technologies could provide additional performance improvements by introducing individualized scene-dependent settings. PMID- 27276991 TI - Dynamic upper airway collapse observed from sleep MRI: BMI-matched severe and mild OSA patients. AB - Dynamic magnetic resonance imaging (MRI) allows real-time characterization of upper airway collapse in sleeping subjects with obstructive sleep apnea (OSA). The aim of our study was to use sleep MRI to compare differences in upper airway collapse sites between BMI-matched subjects with mild OSA and severe OSA. This is a prospective, nested case-control study using dynamic sleep MRI to compare 15 severe OSA subjects (AHI >40) and 15 mild OSA (AHI <10) subjects, who were matched for BMI. Upper airway imaging was performed on sleeping subjects in a 3.0 T MRI scanner. Sleep MRI movies were used by blinded reviewers to identify retropalatal (RP), retroglossal (RG), and lateral pharyngeal wall (LPW) airway collapse. Mean AHI in the severe OSA group was 70.3 +/- 23 events/h, and in the mild group was 7.8 +/- 1 events/h (p < 0.001). All mild and severe OSA subjects demonstrated retropalatal airway collapse. Eighty percent in the mild group showed single-level RP collapse (p < 0.001). All subjects in the severe group showed multi-level collapse: RP + LPW (n = 9), RP + RG + LPW (n = 6). All severe OSA subjects showed LPW collapse, as compared with three subjects in the mild group (p < 0.001). LPW collapse was positively associated with AHI in simple regression analysis (beta = 51.8, p < 0.001). In conclusion, severe OSA patients present with more lateral pharyngeal wall collapse as compared to BMI-matched mild OSA patients. PMID- 27276992 TI - Numerical evaluation of implantable hearing devices using a finite element model of human ear considering viscoelastic properties. AB - Finite element method was employed in this study to analyze the change in performance of implantable hearing devices due to the consideration of soft tissues' viscoelasticity. An integrated finite element model of human ear including the external ear, middle ear and inner ear was first developed via reverse engineering and analyzed by acoustic-structure-fluid coupling. Viscoelastic properties of soft tissues in the middle ear were taken into consideration in this model. The model-derived dynamic responses including middle ear and cochlea functions showed a better agreement with experimental data at high frequencies above 3000 Hz than the Rayleigh-type damping. On this basis, a coupled finite element model consisting of the human ear and a piezoelectric actuator attached to the long process of incus was further constructed. Based on the electromechanical coupling analysis, equivalent sound pressure and power consumption of the actuator corresponding to viscoelasticity and Rayleigh damping were calculated using this model. The analytical results showed that the implant performance of the actuator evaluated using a finite element model considering viscoelastic properties gives a lower output above about 3 kHz than does Rayleigh damping model. Finite element model considering viscoelastic properties was more accurate to numerically evaluate implantable hearing devices. PMID- 27276993 TI - Genomic prediction of crossbred performance based on purebred Landrace and Yorkshire data using a dominance model. AB - BACKGROUND: In pig breeding, selection is usually carried out in purebred populations, although the final goal is to improve crossbred performance. Genomic selection can be used to select purebred parental lines for crossbred performance. Dominance is the likely genetic basis of heterosis and explicitly including dominance in the genomic selection model may be an advantage when selecting purebreds for crossbred performance. Our objectives were two-fold: (1) to compare the predictive ability of genomic prediction models with additive or additive plus dominance effects, when the validation criterion is crossbred performance; and (2) to compare the use of two pure line reference populations to a single combined reference population. METHODS: We used data on litter size in the first parity from two pure pig lines (Landrace and Yorkshire) and their reciprocal crosses. Training was performed (1) separately on pure Landrace (2085) and Yorkshire (2145) sows and (2) the two combined pure lines (4230), which were genotyped for 38 k single nucleotide polymorphisms (SNPs). Prediction accuracy was measured as the correlation between genomic estimated breeding values (GEBV) of pure line boars and mean corrected crossbred-progeny performance, divided by the average accuracy of mean-progeny performance. We evaluated a model with additive effects only (MA) and a model with both additive and dominance effects (MAD). Two types of GEBV were computed: GEBV for purebred performance (GEBV) based on either the MA or MAD models, and GEBV for crossbred performance (GEBV-C) based on the MAD. GEBV-C were calculated based on SNP allele frequencies of genotyped animals in the opposite line. RESULTS: Compared to MA, MAD improved prediction accuracy for both lines. For MAD, GEBV-C improved prediction accuracy compared to GEBV. For Landrace (Yorkshire) boars, prediction accuracies were equal to 0.11 (0.32) for GEBV based on MA, and 0.13 (0.34) and 0.14 (0.36) for GEBV and GEBV-C based on MAD, respectively. Combining animals from both lines into a single reference population yielded higher accuracies than training on each pure line separately. In conclusion, the use of a dominance model increased the accuracy of genomic predictions of crossbred performance based on purebred data. PMID- 27276994 TI - Anodic stripping voltammetry with graphite felt electrodes for the trace analysis of silver. AB - Graphite felt (GF) is a mass produced porous carbon electrode material commonly used in redox flow batteries. Previous studies have suggested GF may have valuable applications in electroanalysis as a low cost disposable carbon electrode material, although most GF sensors have used flow cell arrangements. In this work, an elegant wetting technique is employed that allows GF electrodes to be used in quiescent solution to detect trace levels of silver in water via anodic stripping voltammetry. GF electrodes display good repeatability and a limit of detection of 25 nM of Ag(+) in 0.1 M HNO3, with a linear range spanning two orders of magnitude. This compares to a value of around 140 nM when using conventional carbon electrodes. Combined with their low cost and disposable nature, the results suggest GF electrodes can make a valuable contribution to electroanalysis. PMID- 27276995 TI - Re: Evaluation of Novel Ball-Tip Holmium Laser Fiber: Impact on Ureteroscope Performance and Fragmentation Efficiency (From: Shin RH, Lautz JM, Cabrera FJ, et al. J Endourol 2016;30:189-194). PMID- 27276996 TI - Out of School and Into Distress: Families of Young Adults with Intellectual and Developmental Disabilities in Transition. AB - BACKGROUND: The transition period out of the educational system can be a source of stress for parents of young adults with intellectual and developmental disabilities, as families lose the support and respite offered by schools. MATERIALS AND METHODS: Using a before and after design nested within a 24-month follow-up study of parents seeking adult developmental services for their children, parents' perception of distress was measured using the Brief Family Distress Scale (Journal of Child and Family Studies, 20, 2011, 521) and their perception of helpfulness of formal supports was assessed using the Family Support Scale (Journal of Individual, Family, and Community Wellness, 1, 1984, 45). RESULTS: Parents reported significantly higher levels of distress after their child transitioned out of school. Employed parents and parents of a child with an autism spectrum disorder are at increased risk for distress. CONCLUSIONS: Families fare worse once their adult children are no longer in school, although this is not associated with a reduction in the perception of the helpfulness of formal supports. PMID- 27276997 TI - Temperature dependent local atomic displacements in ammonia intercalated iron selenide superconductor. AB - Recently, ammonia-thermal reaction has been used for molecular intercalation in layered FeSe, resulting a new Lix(NH3)yFe2Se2 superconductor with Tc ~ 45 K. Here, we have used temperature dependent extended x-ray absorption fine structure (EXAFS) to investigate local atomic displacements in single crystals of this new superconductor. Using polarized EXAFS at Fe K-edge we have obtained direct information on the local Fe-Se and Fe-Fe bondlengths and corresponding mean square relative displacements (MSRD). We find that the Se-height in the intercalated system is lower than the one in the binary FeSe, suggesting compressed FeSe4 tetrahedron in the title system. Incidentally, there is hardly any effect of the intercalation on the bondlengths characteristics, revealed by the Einstein temperatures, that are similar to those found in the binary FeSe. Therefore, the molecular intercalation induces an effective compression and decouples the FeSe slabs. Furthermore, the results reveal an anomalous change in the atomic correlations across Tc, appearing as a clear decrease in the MSRD, indicating hardening of the local lattice mode. Similar response of the local lattice has been found in other families of superconductors, e.g., A15-type and cuprates superconductors. This observation suggests that local atomic correlations should have some direct correlation with the superconductivity. PMID- 27276999 TI - PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. AB - BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [ 9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013. PMID- 27276998 TI - Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer's disease: metabolic basis for dementia. AB - Impairment of brain-glucose uptake and brain-copper regulation occurs in Alzheimer's disease (AD). Here we sought to further elucidate the processes that cause neurodegeneration in AD by measuring levels of metabolites and metals in brain regions that undergo different degrees of damage. We employed mass spectrometry (MS) to measure metabolites and metals in seven post-mortem brain regions of nine AD patients and nine controls, and plasma-glucose and plasma copper levels in an ante-mortem case-control study. Glucose, sorbitol and fructose were markedly elevated in all AD brain regions, whereas copper was correspondingly deficient throughout (all P < 0.0001). In the ante-mortem case control study, by contrast, plasma-glucose and plasma-copper levels did not differ between patients and controls. There were pervasive defects in regulation of glucose and copper in AD brain but no evidence for corresponding systemic abnormalities in plasma. Elevation of brain glucose and deficient brain copper potentially contribute to the pathogenesis of neurodegeneration in AD. PMID- 27277000 TI - Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation. AB - BACKGROUND: Increased platelet aggregation is implicated in the pathogenesis of ischemic stroke and anti-platelet strategy may contribute to its therapy. Panaxatriol saponin (PTS), the main components extracted from Panax notoginseng, has been shown to be efficacious in the prevention and treatment of ischemic stroke in China. The aim of this study is to determine the anti-platelet activity and explore the underlying mechanisms. METHODS: Inhibitory effect of PTS and its main ginsenosides on agonists-induced platelet aggregation was determined using rabbit or human platelets. Intracellular Ca(2+) concentration ([Ca(2+)]i) mobilization was detected with fura-2/AM probe. MAPKs phosphorylation was determined by Western blotting. RESULTS: Our results showed PTS inhibited the rabbit platelet aggregation induced by various agonists (collagen, thrombin and ADP). The three main ginsenosides (Rg1, Re and R1) existing in PTS also showed anti-platelet activity, while their combination exhibited no synergistic effect on rabbit platelet aggregation. Further study demonstrated that PTS and its main ginsenosides also exhibited inhibitory effect on human platelet aggregation. Mechanism study demonstrated that pre-treatment with PTS inhibited the agonists induced intracellular calcium mobilization. Moreover, PTS significantly suppressed the activation of both ERK2 and p38 by the agonists via reducing the phosphorylation of ERK2 and p38. CONCLUSION: We proved that PTS is effective in anti-platelet aggregation, which may, at least in part, be related to the suppression of intracellular calcium mobilization and ERK2/p38 activation. This study may provide one reasonable explanation for the efficacy of PTS on the prevention and treatment of ischemic stroke. PMID- 27277004 TI - Deletion upstream of SALL1 producing Townes-Brocks syndrome. PMID- 27277002 TI - Immediate post-operative pain in anterior cruciate ligament reconstruction surgery with bone patellar tendon bone graft versus hamstring graft. AB - BACKGROUND: Pain in the immediate post-operative period after anterior cruciate ligament (ACL) surgery, apart from an unpleasant experience for the patient, can act as a barrier for static quadriceps contractions and optimum execution of the initial rehabilitation protocol resulting in slow recovery and a later return to full function for a sportsperson. There is no report in the literature comparing pain in the immediate post-operative period after using the two most widely used autografts, bone patellar tendon bone (BPTB) graft and hamstring graft. METHODS: The present study compared the visual analogue scale (VAS) pain score in the immediate post-operative period after arthroscopic ACL reconstruction with the BPTB and hamstring autografts. Both groups consisted of 50 patients each. The mean age of the BPTB and hamstring cohorts was 26.9 +/- 7.3 years (age range 18 59 years) and 26.7 +/- 9.0 years (age range 17-52 years), respectively. Unpaired t test was applied to compare pain scores between the BPTB and hamstring cohorts. RESULTS: In the present study, patients in the BPTB cohort showed higher mean pain scores across all the post-operative time intervals except at 6 h. However, the difference in the mean VAS pain score at post-operative 6, 12,18, 24, 36 and 48 h in the two groups was statistically not significant (p value of 1, 0.665, 0.798, 0.377, 0.651 and 0.215 at 6, 12, 18, 24, 36 and 48 h, respectively). CONCLUSIONS: Our study concludes that the arthroscopic ACL reconstruction with BPTB autograft and hamstring autograft is associated with similar pain in the immediate post-operative period. As a result, aggressive physiotherapy regime is not affected by the type of graft being used for ACL reconstruction, as the pain scores in the immediate post-operative period are similar for both techniques. TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2016/01/006502. PMID- 27277005 TI - Daniel R. Mishell Jr, MD, May 7, 1931-May 4, 2016. PMID- 27277001 TI - Food, health, and complexity: towards a conceptual understanding to guide collaborative public health action. AB - BACKGROUND: What we eat simultaneously impacts our exposure to pathogens, allergens, and contaminants, our nutritional status and body composition, our risks for and the progression of chronic diseases, and other outcomes. Furthermore, what we eat is influenced by a complex web of drivers, including culture, politics, economics, and our built and natural environments. To date, public health initiatives aimed at improving food-related population health outcomes have primarily been developed within 'practice silos', and the potential for complex interactions among such initiatives is not well understood. Therefore, our objective was to develop a conceptual model depicting how infectious foodborne illness, food insecurity, dietary contaminants, obesity, and food allergy can be linked via shared drivers, to illustrate potential complex interactions and support future collaboration across public health practice silos. METHODS: We developed the conceptual model by first conducting a systematic literature search to identify review articles containing schematics that depicted relationships between drivers and the issues of interest. Next, we synthesized drivers into a common model using a modified thematic synthesis approach that combined an inductive thematic analysis and mapping to synthesize findings. RESULTS: The literature search yielded 83 relevant references containing 101 schematics. The conceptual model contained 49 shared drivers and 227 interconnections. Each of the five issues was connected to all others. Obesity and food insecurity shared the most drivers (n = 28). Obesity shared several drivers with food allergy (n = 11), infectious foodborne illness (n = 7), and dietary contamination (n = 6). Food insecurity shared several drivers with infectious foodborne illness (n = 9) and dietary contamination (n = 9). Infectious foodborne illness shared drivers with dietary contamination (n = 8). Fewer drivers were shared between food allergy and: food insecurity (n = 4); infectious foodborne illness (n = 2); and dietary contamination (n = 1). CONCLUSIONS: Our model explicates potential interrelationships between five population health issues for which public health interventions have historically been siloed, suggesting that interventions targeted towards these issues have the potential to interact and produce unexpected consequences. Public health practitioners working in infectious foodborne illness, food insecurity, dietary contaminants, obesity, and food allergy should actively consider how their seemingly targeted public health actions may produce unintended positive or negative population health impacts. PMID- 27277003 TI - Modulation of the sympathetic nervous system by renal denervation prevents reduction of aortic distensibility in atherosclerosis prone ApoE-deficient rats. AB - BACKGROUND: Apolipoprotein E-deficient (ApoE(-/-)) rodents spontaneously develop severe hypercholesterolemia and increased aortic stiffness, both accepted risk factors for cardiovascular morbidity and mortality in humans. In patients with resistant hypertension renal denervation (RDN) may improve arterial stiffness, however the underlying mechanisms are incompletely understood. This study investigates the impact of RDN on aortic compliance in a novel atherosclerosis prone ApoE(-/-)-rat model. METHODS: Normotensive, 8 weeks old ApoE(-/-) and Sprague-Dawley (SD) rats were subjected to bilateral surgical RDN (n = 6 per group) or sham operation (n = 5 per group) and fed with normal chow for 8 weeks. Compliance of the ascending aorta was assessed by magnetic resonance imaging. Vasomotor function was measured by aortic ring tension recordings. Aortic collagen content was quantified histologically and plasma aldosterone levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: After 8 weeks, ApoE(-/-)-sham demonstrated a 58 % decrease in aortic distensibility when compared with SD-sham (0.0051 +/- 0.0011 vs. 0.0126 +/- 0.0023 1/mmHg; p = 0.02). This was accompanied by an impaired endothelium-dependent relaxation of aortic rings and an increase in aortic medial fibrosis (17.87 +/- 1.4 vs. 12.27 +/- 1.1 %; p = 0.006). In ApoE(-/-)-rats, RDN prevented the reduction of aortic distensibility (0.0128 +/- 0.002 vs. 0.0051 +/- 0.0011 1/mmHg; p = 0.01), attenuated endothelial dysfunction, and decreased aortic medial collagen content (12.71 +/- 1.3 vs. 17.87 +/- 1.4 %; p = 0.01) as well as plasma aldosterone levels (136.33 +/- 6.6 vs. 75.52 +/- 8.4 pg/ml; p = 0.0003). Cardiac function and metabolic parameters such as hypercholesterolemia were not influenced by RDN. CONCLUSION: ApoE(-/-)-rats spontaneously develop impaired vascular compliance. RDN improves aortic distensibility and attenuated endothelial dysfunction in ApoE(-/-)-rats. This was associated with a reduction in aortic fibrosis formation, and plasma aldosterone levels. PMID- 27277006 TI - Sorokiniol: a new enzymes inhibitory metabolite from fungal endophyte Bipolaris sorokiniana LK12. AB - BACKGROUND: Medicinal plants harboring endophytic fungi could carry significant potential for producing bioactive secondary metabolites. Endophytic fungi serve as alternate source of interesting compounds in their natural and modified synthetic forms to treat different diseases. In this regard, endophytic microflora associated with alkaloid-rich medicinal plants Rhazya stricta is least known. RESULTS: We isolated one new bioactive compound sorokiniol (1) along with two known cyclic peptides BZR-cotoxin I (2) and BZR-cotoxin IV (3) from fungal endophyte Bipolaris sorokiniana LK12. The structures of the isolated new and known compounds were elucidated through spectroscopic data, including 1D and 2D NMR ((1)H, (13)C, HSQC, HMBC, and NOESY), mass, and UV. The known peptides (2-3) were characterized by ESI-MS, MS/MS, and by comparing the NMR data with the literature. The isolated metabolites were assayed for their role against enzyme inhibition. Compound 1 was significantly inhibitory towards acetyl cholinestrase while the other compounds (2-3) had moderate anti-lipid peroxidation and urease activities. CONCLUSION: The present results suggest that the endophytic microorganism associated with indigenously important medicinal plants can offer a rich source of biologically active chemical constituents which could help in discovering enzyme inhibitory lead drugs. PMID- 27277007 TI - Management challenges with brown tumor of primary hyperparathyroidism masked by severe vitamin D deficiency: a case report. AB - BACKGROUND: Hyperparathyroidism is a disease characterized by excessive secretion of parathyroid hormone, the hormone responsible for calcium and phosphate homeostasis in the body. It can be of three types: primary, secondary, or tertiary. It is essential to bear in mind that in any one patient more than one type of hyperparathyroidism may be found, which may create perplexity regarding the etiology of the case. Hyperparathyroidism can become apparent early in its course when a patient presents with symptoms of abdominal pain, recurrent renal calculi, repeated fractures, or behavior changes. It is generally accepted that bone involvement is a late manifestation of primary hyperparathyroidism. It is imperative to consider that some patients, such as our patient described in this report, may be previously asymptomatic clinically and on the basis of laboratory findings and present with only late skeletal manifestations. Brown tumors are one of the mimickers of lytic lesions of the jaw and need to be ruled out early in the course of management. Researchers in several studies published in high-impact journals have recommended the use of high-dose vitamin D as safe in patients with primary hyperparathyroidism without the risk of raising calcium levels significantly. In our patient, we observed considerable hypercalcemia after high dose vitamin D therapy, and we propose exercising discretion with the use of high dose therapies. CASE PRESENTATION: We report a case of a 21-year-old Arab woman with a brown tumor who presented with hypocalcaemia. She presented with a mixed picture of primary hyperparathyroidism and severe vitamin D deficiency. CONCLUSIONS: Brown tumors, although thought to be a forgotten entity with the advent of early screening for hypercalcemia, is still prevalent, as a handful of patients may present late in the disease course with no early markers, such as in our patient. We emphasize using a holistic approach for early diagnosis and adopting a restricted attitude to treating these benign entities, especially in the context of cosmesis for sensitive locations such as the face. In addition, we express caution in using daily supplementation with a high vitamin D dose to improve vitamin D status and decrease parathyroid hormone. PMID- 27277008 TI - Perichondrium mesenchymal stem cells inhibit the growth of breast cancer cells via the DKK-1/Wnt/beta-catenin signaling pathway. AB - In recent years, mesenchymal stem cells (MSCs), which possess the ability to specifically home to tumor sites, with the potential of multi-directional differentiation and low immunogenicity, have been reported to inhibit the growth of various types of tumors. In the present study, we isolated MSCs from the rib perichondrium (PMSCs). By comparing PMSCs with bone marrow-derived mesenchymal stem cells (BMSCs), we demonstrated that PMSCs present biological characteristics similar to those of BMSCs. Furthermore, we explored the effect and antitumor mechanism of PMSCs in rat SHZ-88 breast cancer cells. The growth, migration and invasion of the SHZ-88 cells were significantly inhibited, and the Wnt/beta catenin pathway and its target genes were downregulated in the SHZ-88 cells by PMSC-conditioned medium. The expression level of dickkopf-1 (DKK-1) was higher in the PMSCs than that noted in the SHZ-88 cells. Neutralization of DKK-1 in the PMSC-conditioned medium attenuated the inhibitory effects of PMSCs on SHZ-88 cells. Therefore, PMSC-secreted DKK-1 is involved in the inhibition of SHZ-88 cell growth, migration and invasion, via the Wnt/beta-catenin signaling pathway. In addition, we demonstrated that PMSCs inhibited the growth of breast cancer in vivo and prolonged the survival time of tumor-bearing rats. PMSCs inhibited the growth of transplanted breast tumors through the Wnt/beta-catenin signaling pathway. In conclusion, our data confirmed that MSCs derived from the perichondrium present biological characteristics similar to those of BMSCs and inhibit the growth of breast cancer cells through the Wnt/beta-catenin signaling pathway in vitro and in vivo. DKK-1 secreted by PMSCs played a vital role in controlling the Wnt/beta-catenin signaling pathway in breast cancer. PMID- 27277011 TI - Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring. AB - Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy in offspring. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow diet. At postnatal Week 8, offspring were randomly administered low dose streptozotocin (STZ, 55 mg/kg/day for five days) to induce diabetes. Assessment of renal damage took place at postnatal Week 32. We found that offspring of obese mothers had increased renal fibrosis, inflammation and oxidative stress. Importantly, offspring exposed to maternal obesity had increased susceptibility to renal damage when an additional insult, such as STZ induced diabetes, was imposed. Specifically, renal inflammation and oxidative stress induced by diabetes was augmented by maternal obesity. Our findings suggest that developmental programming induced by maternal obesity has implications for renal health in offspring. Maternal obesity should be considered a risk factor for CKD. PMID- 27277013 TI - Effects of previous episodes of influenza and vaccination in preventing laboratory-confirmed influenza in Navarre, Spain, 2013/14 season. AB - We estimated whether previous episodes of influenza and trivalent influenza vaccination prevented laboratory-confirmed influenza in Navarre, Spain, in season 2013/14. Patients with medically-attended influenza-like illness (MA-ILI) in hospitals (n = 645) and primary healthcare (n = 525) were included. We compared 589 influenza cases and 581 negative controls. MA-ILI related to a specific virus subtype in the previous five seasons was defined as a laboratory-confirmed influenza infection with the same virus subtype or MA-ILI during weeks when more than 25% of swabs were positive for this subtype. Persons with previous MA-ILI had 30% (95% confidence interval (CI): -7 to 54) lower risk of MA-ILI, and those with previous MA-ILI related to A(H1N1)pdm09 or A(H3N2) virus, had a, respectively, 63% (95% CI: 16-84) and 65% (95% CI: 13-86) lower risk of new laboratory-confirmed influenza by the same subtype. Overall adjusted vaccine effectiveness in preventing laboratory-confirmed influenza was 31% (95% CI: 5 50): 45% (95% CI: 12-65) for A(H1N1)pdm09 and 20% (95% CI: -16 to 44) for A(H3N2). While a previous influenza episode induced high protection only against the same virus subtype, influenza vaccination provided low to moderate protection against all circulating subtypes. Influenza vaccine remains the main preventive option for high-risk populations. PMID- 27277012 TI - The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats. AB - The programmed cell death-1(PD-1)/PD-ligand 1 (PD-L1) pathway is critical to immune homeostasis by promoting regulatory T (Treg) development and inhibiting effector T (such as Th17) cell responses. However, the association between the PD 1/PD-L1 pathway and the Treg/Th17 imbalance has not been fully investigated in pre-eclampsia (PE). In this study, we observed an inverse correlation between the percentages of Treg and Th17 cells, and the expression of PD-1 and PD-L1 on the two subsets also changed in PE compared with normal pregnancy. We further explored their relationship in vivo using the L-NG-Nitroarginine Methyl Ester (L NAME) induced PE-like rat models, also characterized by Treg/Th17 imbalance. Administration of PD-L1-Fc protein provides a protective effects on the pre eclamptic models, both to the mother and the fetuses, by reversing Treg/Th17 imbalance through inhibiting PI3K/AKT/m-TOR signaling and enhancing PTEN expression. In addition, we also observed a protective effect of PD-L1-Fc on the placenta by reversing placental damages. These results suggested that altered PD 1/PD-L1 pathway contributed to Treg/Th17 imbalance in PE. Treatment with PD-L1-Fc posed protective effects on pre-eclamptic models, indicating that the use of PD L1-Fc might be a potential therapeutic target in PE treatment. PMID- 27277015 TI - EPID-based daily quality assurance of linear accelerators will likely replace other methods within the next ten years. PMID- 27277014 TI - SCOUP: a probabilistic model based on the Ornstein-Uhlenbeck process to analyze single-cell expression data during differentiation. AB - BACKGROUND: Single-cell technologies make it possible to quantify the comprehensive states of individual cells, and have the power to shed light on cellular differentiation in particular. Although several methods have been developed to fully analyze the single-cell expression data, there is still room for improvement in the analysis of differentiation. RESULTS: In this paper, we propose a novel method SCOUP to elucidate differentiation process. Unlike previous dimension reduction-based approaches, SCOUP describes the dynamics of gene expression throughout differentiation directly, including the degree of differentiation of a cell (in pseudo-time) and cell fate. SCOUP is superior to previous methods with respect to pseudo-time estimation, especially for single cell RNA-seq. SCOUP also successfully estimates cell lineage more accurately than previous method, especially for cells at an early stage of bifurcation. In addition, SCOUP can be applied to various downstream analyses. As an example, we propose a novel correlation calculation method for elucidating regulatory relationships among genes. We apply this method to a single-cell RNA-seq data and detect a candidate of key regulator for differentiation and clusters in a correlation network which are not detected with conventional correlation analysis. CONCLUSIONS: We develop a stochastic process-based method SCOUP to analyze single-cell expression data throughout differentiation. SCOUP can estimate pseudo-time and cell lineage more accurately than previous methods. We also propose a novel correlation calculation method based on SCOUP. SCOUP is a promising approach for further single-cell analysis and available at https://github.com/hmatsu1226/SCOUP. PMID- 27277016 TI - Improving lung cancer prognosis assessment by incorporating synthetic minority oversampling technique and score fusion method. AB - PURPOSE: This study aims to investigate the potential to improve lung cancer recurrence risk prediction performance for stage I NSCLS patients by integrating oversampling, feature selection, and score fusion techniques and develop an optimal prediction model. METHODS: A dataset involving 94 early stage lung cancer patients was retrospectively assembled, which includes CT images, nine clinical and biological (CB) markers, and outcome of 3-yr disease-free survival (DFS) after surgery. Among the 94 patients, 74 remained DFS and 20 had cancer recurrence. Applying a computer-aided detection scheme, tumors were segmented from the CT images and 35 quantitative image (QI) features were initially computed. Two normalized Gaussian radial basis function network (RBFN) based classifiers were built based on QI features and CB markers separately. To improve prediction performance, the authors applied a synthetic minority oversampling technique (SMOTE) and a BestFirst based feature selection method to optimize the classifiers and also tested fusion methods to combine QI and CB based prediction results. RESULTS: Using a leave-one-case-out cross-validation (K-fold cross validation) method, the computed areas under a receiver operating characteristic curve (AUCs) were 0.716 +/- 0.071 and 0.642 +/- 0.061, when using the QI and CB based classifiers, respectively. By fusion of the scores generated by the two classifiers, AUC significantly increased to 0.859 +/- 0.052 (p < 0.05) with an overall prediction accuracy of 89.4%. CONCLUSIONS: This study demonstrated the feasibility of improving prediction performance by integrating SMOTE, feature selection, and score fusion techniques. Combining QI features and CB markers and performing SMOTE prior to feature selection in classifier training enabled RBFN based classifier to yield improved prediction accuracy. PMID- 27277017 TI - Method for simulating dose reduction in digital mammography using the Anscombe transformation. AB - PURPOSE: This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. METHODS: The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. RESULTS: The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. CONCLUSIONS: A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions. PMID- 27277018 TI - Technical Note: Impact of cell repopulation and radionuclide uptake phase on cell survival. AB - PURPOSE: To study theoretically the impact on cell survival of the radionuclide uptake rate inside tumor cells for a single administration of a radiopharmaceutical. METHODS: The instantaneous-uptake model of O'Donoghue ["The impact of tumor cell proliferation in radioimmunotherapy," Cancer 73, 974-980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is here extended to allow for the monoexponential uptake of the radiopharmaceutical by the targeted cells. The time derivative of the survival curve is studied in detail deducing an expression for the minimum of the surviving fraction and the biologically effective dose (BED). RESULTS: Surviving fractions are calculated over a parameter range that is clinically relevant and broad enough to establish general trends. Specifically, results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1-24 h, extrapolated initial dose-rates 0.5-1 Gy h(-1), and a biological clearance half-life of seven days. Representative radiobiological parameters for radiosensitive and rapidly proliferating tumor cells are used, with cell doubling time equal to 2 days and alpha-coefficient equal to 0.3 and 0.5 Gy(-1). It is shown that neglecting the uptake phase of the radiopharmaceutical (i.e., assuming instantaneous-uptake) results in a sizeable over-estimation of cell-kill (i.e., under-estimation of cell survival) even for uptake half-times of only a few hours. The differences between the exponential-uptake model and the instantaneous uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for long-lived radionuclides. Moreover, the sensitivity of the survival curve on the uptake model was found to be higher for the tumor cells with the larger alpha coefficient. CONCLUSIONS: The exponential-uptake rate of the radiopharmaceutical inside targeted cells appears to have a considerable effect on the survival of a proliferating cell population and might need to be considered in radiobiological models of tumor cell-kill in radionuclide therapy. PMID- 27277019 TI - Interindividual registration and dose mapping for voxelwise population analysis of rectal toxicity in prostate cancer radiotherapy. AB - PURPOSE: Recent studies revealed a trend toward voxelwise population analysis in order to understand the local dose/toxicity relationships in prostate cancer radiotherapy. Such approaches require, however, an accurate interindividual mapping of the anatomies and 3D dose distributions toward a common coordinate system. This step is challenging due to the high interindividual variability. In this paper, the authors propose a method designed for interindividual nonrigid registration of the rectum and dose mapping for population analysis. METHODS: The method is based on the computation of a normalized structural description of the rectum using a Laplacian-based model. This description takes advantage of the tubular structure of the rectum and its centerline to be embedded in a nonrigid registration-based scheme. The performances of the method were evaluated on 30 individuals treated for prostate cancer in a leave-one-out cross validation. RESULTS: Performance was measured using classical metrics (Dice score and Hausdorff distance), along with new metrics devised to better assess dose mapping in relation with structural deformation (dose-organ overlap). Considering these scores, the proposed method outperforms intensity-based and distance maps-based registration methods. CONCLUSIONS: The proposed method allows for accurately mapping interindividual 3D dose distributions toward a single anatomical template, opening the way for further voxelwise statistical analysis. PMID- 27277020 TI - Characterization of scintillator-based detectors for few-ten-keV high-spatial resolution x-ray imaging. AB - PURPOSE: High-spatial-resolution x-ray imaging in the few-ten-keV range is becoming increasingly important in several applications, such as small-animal imaging and phase-contrast imaging. The detector properties critically influence the quality of such imaging. Here the authors present a quantitative comparison of scintillator-based detectors for this energy range and at high spatial frequencies. METHODS: The authors determine the modulation transfer function, noise power spectrum (NPS), and detective quantum efficiency for Gadox, needle CsI, and structured CsI scintillators of different thicknesses and at different photon energies. An extended analysis of the NPS allows for direct measurements of the scintillator effective absorption efficiency and effective light yield as well as providing an alternative method to assess the underlying factors behind the detector properties. RESULTS: There is a substantial difference in performance between the scintillators depending on the imaging task but in general, the CsI based scintillators perform better than the Gadox scintillators. At low energies (16 keV), a thin needle CsI scintillator has the best performance at all frequencies. At higher energies (28-38 keV), the thicker needle CsI scintillators and the structured CsI scintillator all have very good performance. The needle CsI scintillators have higher absorption efficiencies but the structured CsI scintillator has higher resolution. CONCLUSIONS: The choice of scintillator is greatly dependent on the imaging task. The presented comparison and methodology will assist the imaging scientist in optimizing their high resolution few-ten-keV imaging system for best performance. PMID- 27277021 TI - Simultaneous extraction of endocardial and epicardial contours of the left ventricle by distance regularized level sets. AB - PURPOSE: Segmentation of the cardiac left ventricle (LV) is still an open problem and is challenging due to the poor contrast between tissues around the epicardium and image artifacts. To extract the endocardium and epicardium of the cardiac left ventricle accurately, the authors propose a two-layer level set approach for segmentation of the LV from cardiac magnetic resonance short-axis images. METHODS: In the proposed method, the endocardium and epicardium are represented by two specified level contours of a level set function. Segmentation of the LV is formulated as a problem of optimizing the level set function such that these two level contours best fit the epicardium and endocardium, subject to a distance regularization (DR) term to preserve a smoothly varying distance between them. The DR term introduces a desirable interaction between the two level contours of a single level set function, which contributes to preserve the anatomical geometry of the epicardium and endocardium of the LV. In addition, the proposed method has an intrinsic ability to deal with intensity inhomogeneity in MR images, which is a common image artifact in MRI. RESULTS: Their method is quantitatively validated by experiments on the datasets for the MICCAI 2009 grand challenge on left ventricular segmentation and the MICCAI 2013 challenge workshop on segmentation: algorithms, theory and applications (SATA). To overcome discontinuity of 2D segmentation results at some adjacent slices for a few cases, the authors extend distance regularized two-layer level set to 3D to refine the segmentation results. The corresponding metrics for their method are better than the methods in the MICCAI 2009 challenge. Their method was ranked at the first place in terms of Hausdorff distance and the second place in terms of Dice similarity coefficient in the MICCAI 2013 challenge. CONCLUSIONS: Experimental results demonstrate the advantages of their method in terms of segmentation accuracy and consistency with the heart anatomy. PMID- 27277022 TI - Technical Note: A fast online adaptive replanning method for VMAT using flattening filter free beams. AB - PURPOSE: To develop a fast replanning algorithm based on segment aperture morphing (SAM) for online replanning of volumetric modulated arc therapy (VMAT) with flattening filter free (FFF) beams. METHODS: A software tool was developed to interface with a VMAT research planning system, which enables the input and output of beam and machine parameters of VMAT plans. The SAM algorithm was used to modify multileaf collimator positions for each segment aperture based on the changes of the target from the planning (CT/MR) to daily image [CT/CBCT/magnetic resonance imaging (MRI)]. The leaf travel distance was controlled for large shifts to prevent the increase of VMAT delivery time. The SAM algorithm was tested for 11 patient cases including prostate, pancreatic, and lung cancers. For each daily image set, three types of VMAT plans, image-guided radiation therapy (IGRT) repositioning, SAM adaptive, and full-scope reoptimization plans, were generated and compared. RESULTS: The SAM adaptive plans were found to have improved the plan quality in target and/or critical organs when compared to the IGRT repositioning plans and were comparable to the reoptimization plans based on the data of planning target volume (PTV)-V100 (volume covered by 100% of prescription dose). For the cases studied, the average PTV-V100 was 98.85% +/- 1.13%, 97.61% +/- 1.45%, and 92.84% +/- 1.61% with FFF beams for the reoptimization, SAM adaptive, and repositioning plans, respectively. The execution of the SAM algorithm takes less than 10 s using 16-CPU (2.6 GHz dual core) hardware. CONCLUSIONS: The SAM algorithm can generate adaptive VMAT plans using FFF beams with comparable plan qualities as those from the full-scope reoptimization plans based on daily CT/CBCT/MRI and can be used for online replanning to address interfractional variations. PMID- 27277023 TI - Noise power spectrum of the fixed pattern noise in digital radiography detectors. AB - PURPOSE: The fixed pattern noise in radiography image detectors is caused by various sources. Multiple readout circuits with gate drivers and charge amplifiers are used to efficiently acquire the pixel voltage signals. However, the multiple circuits are not identical and thus yield nonuniform system gains. Nonuniform sensitivities are also produced from local variations in the charge collection elements. Furthermore, in phosphor-based detectors, the optical scattering at the top surface of the columnar CsI growth, the grain boundaries, and the disorder structure causes spatial sensitivity variations. These nonuniform gains or sensitivities cause fixed pattern noise and degrade the detector performance, even though the noise problem can be partially alleviated by using gain correction techniques. Hence, in order to develop good detectors, comparative analysis of the energy spectrum of the fixed pattern noise is important. METHODS: In order to observe the energy spectrum of the fixed pattern noise, a normalized noise power spectrum (NNPS) of the fixed pattern noise is considered in this paper. Since the fixed pattern noise is mainly caused by the nonuniform gains, we call the spectrum the gain NNPS. We first asymptotically observe the gain NNPS and then formulate two relationships to calculate the gain NNPS based on a nonuniform-gain model. Since the gain NNPS values are quite low compared to the usual NNPS, measuring such a low NNPS value is difficult. By using the average of the uniform exposure images, a robust measuring method for the gain NNPS is proposed in this paper. RESULTS: By using the proposed measuring method, the gain NNPS curves of several prototypes of general radiography and mammography detectors were measured to analyze their fixed pattern noise properties. We notice that a direct detector, which is based on the a-Se photoconductor, showed lower gain NNPS than the indirect-detector case, which is based on the CsI scintillator. By comparing the gain NNPS curves of the indirect detectors, we could analyze the scintillator properties depending on the techniques for the scintillator surface processing. CONCLUSIONS: A robust measuring method for the NNPS of the fixed pattern noise of a radiography detector is proposed in this paper. The method can measure a stable gain NNPS curve, even though the fixed pattern noise level is quite low. From the measured gain NNPS curves, we can compare and analyze the detector properties in terms of producing the fixed pattern noise. PMID- 27277024 TI - A beam hardening and dispersion correction for x-ray dark-field radiography. AB - PURPOSE: X-ray dark-field imaging promises information on the small angle scattering properties even of large samples. However, the dark-field image is correlated with the object's attenuation and phase-shift if a polychromatic x-ray spectrum is used. A method to remove part of these correlations is proposed. METHODS: The experimental setup for image acquisition was modeled in a wave-field simulation to quantify the dark-field signals originating solely from a material's attenuation and phase-shift. A calibration matrix was simulated for ICRU46 breast tissue. Using the simulated data, a dark-field image of a human mastectomy sample was corrected for the finger print of attenuation- and phase image. RESULTS: Comparing the simulated, attenuation-based dark-field values to a phantom measurement, a good agreement was found. Applying the proposed method to mammographic dark-field data, a reduction of the dark-field background and anatomical noise was achieved. The contrast between microcalcifications and their surrounding background was increased. CONCLUSIONS: The authors show that the influence of and dispersion can be quantified by simulation and, thus, measured image data can be corrected. The simulation allows to determine the corresponding dark-field artifacts for a wide range of setup parameters, like tube-voltage and filtration. The application of the proposed method to mammographic dark-field data shows an increase in contrast compared to the original image, which might simplify a further image-based diagnosis. PMID- 27277025 TI - Technical Note: Improving proton stopping power ratio determination for a deformable silicone-based 3D dosimeter using dual energy CT. AB - PURPOSE: The aim of this study was to investigate whether the stopping power ratio (SPR) of a deformable, silicone-based 3D dosimeter could be determined more accurately using dual energy (DE) CT compared to using conventional methods based on single energy (SE) CT. The use of SECT combined with the stoichiometric calibration method was therefore compared to DECT-based determination. METHODS: The SPR of the dosimeter was estimated based on its Hounsfield units (HUs) in both a SECT image and a DECT image set. The stoichiometric calibration method was used for converting the HU in the SECT image to a SPR value for the dosimeter while two published SPR calibration methods for dual energy were applied on the DECT images. Finally, the SPR of the dosimeter was measured in a 60 MeV proton by quantifying the range difference with and without the dosimeter in the beam path. RESULTS: The SPR determined from SECT and the stoichiometric method was 1.10, compared to 1.01 with both DECT calibration methods. The measured SPR for the dosimeter material was 0.97. CONCLUSIONS: The SPR of the dosimeter was overestimated by 13% using the stoichiometric method and by 3% when using DECT. If the stoichiometric method should be applied for the dosimeter, the HU of the dosimeter must be manually changed in the treatment planning system in order to give a correct SPR estimate. Using a wrong SPR value will cause differences between the calculated and the delivered treatment plans. PMID- 27277027 TI - Technical Note: Validation and implementation of a wireless transponder tracking system for gated stereotactic ablative radiotherapy of the liver. AB - PURPOSE: Tracking soft-tissue targets has recently been cleared as a new application of Calypso, an electromagnetic wireless transponder tracking system, allowing for gated treatment of the liver based on the motion of the target volume itself. The purpose of this study is to describe the details of validating the Calypso system for wireless transponder tracking of the liver and to present the clinical workflow for using it to deliver gated stereotactic ablative radiotherapy (SABR). METHODS: A commercial 3D diode array motion system was used to evaluate the dynamic tracking accuracy of Calypso when tracking continuous large amplitude motion. It was then used to perform end-to-end tests to evaluate the dosimetric accuracy of gated beam delivery for liver SABR. In addition, gating limits were investigated to determine how large the gating window can be while still maintaining dosimetric accuracy. The gating latency of the Calypso system was also measured using a customized motion phantom. RESULTS: The average absolute difference between the measured and expected positional offset was 0.3 mm. The 2%/2 mm gamma pass rates for the gated treatment delivery were greater than 97%. When increasing the gating limits beyond the known extent of planned motion, the gamma pass rates decreased as expected. The 2%/2 mm gamma pass rate for a 1, 2, and 3 mm increase in gating limits was measured to be 97.8%, 82.9%, and 61.4%, respectively. The average gating latency was measured to be 63.8 ms for beam-hold and 195.8 ms for beam-on. Four liver patients with 17 total fractions have been successfully treated at our institution. CONCLUSIONS: Wireless transponder tracking was validated as a dosimetrically accurate way to provide gated SABR of the liver. The dynamic tracking accuracy of the Calypso system met manufacturer's specification, even for continuous large amplitude motion that can be encountered when tracking liver tumors close to the diaphragm. The measured beam-hold gating latency was appropriate for targets that will traverse the gating limit each respiratory cycle causing the beam to be interrupted constantly throughout treatment delivery. PMID- 27277026 TI - Spatial and rotational quality assurance of 6DOF patient tracking systems. AB - PURPOSE: External tracking systems used for patient positioning and motion monitoring during radiotherapy are now capable of detecting both translations and rotations. In this work, the authors develop a novel technique to evaluate the 6 degree of freedom 6(DOF) (translations and rotations) performance of external motion tracking systems. The authors apply this methodology to an infrared marker tracking system and two 3D optical surface mapping systems in a common tumor 6DOF workspace. METHODS: An in-house designed and built 6DOF parallel kinematics robotic motion phantom was used to perform motions with sub-millimeter and subdegree accuracy in a 6DOF workspace. An infrared marker tracking system was first used to validate a calibration algorithm which associates the motion phantom coordinate frame to the camera frame. The 6DOF positions of the mobile robotic system in this space were then tracked and recorded independently by an optical surface tracking system after a cranial phantom was rigidly fixed to the moveable platform of the robotic stage. The calibration methodology was first employed, followed by a comprehensive 6DOF trajectory evaluation, which spanned a full range of positions and orientations in a 20 * 20 * 16 mm and 5 degrees * 5 degrees * 5 degrees workspace. The intended input motions were compared to the calibrated 6DOF measured points. RESULTS: The technique found the accuracy of the infrared (IR) marker tracking system to have maximal root-mean square error (RMSE) values of 0.18, 0.25, 0.07 mm, 0.05 degrees , 0.05 degrees , and 0.09 degrees in left-right (LR), superior-inferior (SI), anterior-posterior (AP), pitch, roll, and yaw, respectively, comparing the intended 6DOF position and the measured position by the IR camera. Similarly, the 6DOF RSME discrepancy for the HD optical surface tracker yielded maximal values of 0.46, 0.60, 0.54 mm, 0.06 degrees , 0.11 degrees , and 0.08 degrees in LR, SI, AP, pitch, roll, and yaw, respectively, over the same 6DOF evaluative workspace. An earlier generation 3D optical surface tracking unit was observed to have worse tracking capabilities than both the IR camera unit and the newer 3D surface tracking system with maximal RMSE of 0.69, 0.74, 0.47 mm, 0.28 degrees , 0.19 degrees , and 0.18 degrees , in LR, SI, AP, pitch, roll, and yaw, respectively, in the same 6DOF evaluation space. CONCLUSIONS: The proposed technique was found to be effective at evaluating the performance of 6DOF patient tracking systems. All observed optical tracking systems were found to exhibit tracking capabilities at the sub millimeter and subdegree level within a 6DOF workspace. PMID- 27277028 TI - Technical Note: High temporal resolution characterization of gating response time. AB - PURPOSE: Low temporal latency between a gating ON/OFF signal and the LINAC beam ON/OFF during respiratory gating is critical for patient safety. Here the authors describe a novel method to precisely measure gating lag times at high temporal resolutions. METHODS: A respiratory gating simulator with an oscillating platform was modified to include a linear potentiometer for position measurement. A photon diode was placed at linear accelerator isocenter for beam output measurement. The output signals of the potentiometer and diode were recorded simultaneously at 2500 Hz with an analog to digital converter for four different commercial respiratory gating systems. The ON and OFF of the beam signal were located and compared to the expected gating window for both phase and position based gating and the temporal lag times extracted. RESULTS: For phase based gating, a real time position management (RPM) infrared marker tracking system with a single camera and a RPM system with a stereoscopic camera were measured to have mean gate ON/OFF lag times of 98/90 and 86/44 ms, respectively. For position based gating, an AlignRT 3D surface system and a Calypso magnetic fiducial tracking system were measured to have mean gate ON/OFF lag times of 356/529 and 209/60 ms, respectively. CONCLUSIONS: Temporal resolution of the method was high enough to allow characterization of individual gate cycles and was primary limited by the sampling speed of the data recording device. Significant variation of mean gate ON/OFF lag time was found between different gating systems. For certain gating devices, individual gating cycle lag times can vary significantly. PMID- 27277030 TI - Automated detection of pulmonary nodules in PET/CT images: Ensemble false positive reduction using a convolutional neural network technique. AB - PURPOSE: Automated detection of solitary pulmonary nodules using positron emission tomography (PET) and computed tomography (CT) images shows good sensitivity; however, it is difficult to detect nodules in contact with normal organs, and additional efforts are needed so that the number of false positives (FPs) can be further reduced. In this paper, the authors propose an improved FP reduction method for the detection of pulmonary nodules in PET/CT images by means of convolutional neural networks (CNNs). METHODS: The overall scheme detects pulmonary nodules using both CT and PET images. In the CT images, a massive region is first detected using an active contour filter, which is a type of contrast enhancement filter that has a deformable kernel shape. Subsequently, high-uptake regions detected by the PET images are merged with the regions detected by the CT images. FP candidates are eliminated using an ensemble method; it consists of two feature extractions, one by shape/metabolic feature analysis and the other by a CNN, followed by a two-step classifier, one step being rule based and the other being based on support vector machines. RESULTS: The authors evaluated the detection performance using 104 PET/CT images collected by a cancer screening program. The sensitivity in detecting candidates at an initial stage was 97.2%, with 72.8 FPs/case. After performing the proposed FP-reduction method, the sensitivity of detection was 90.1%, with 4.9 FPs/case; the proposed method eliminated approximately half the FPs existing in the previous study. CONCLUSIONS: An improved FP-reduction scheme using CNN technique has been developed for the detection of pulmonary nodules in PET/CT images. The authors' ensemble FP-reduction method eliminated 93% of the FPs; their proposed method using CNN technique eliminates approximately half the FPs existing in the previous study. These results indicate that their method may be useful in the computer-aided detection of pulmonary nodules using PET/CT images. PMID- 27277029 TI - Characterizing spatiotemporal information loss in sparse-sampling-based dynamic MRI for monitoring respiration-induced tumor motion in radiotherapy. AB - PURPOSE: Sparse-sampling and reconstruction techniques represent an attractive strategy to achieve faster image acquisition speeds, while maintaining adequate spatial resolution and signal-to-noise ratio in rapid magnetic resonance imaging (MRI). The authors investigate the use of one such sequence, broad-use linear acquisition speed-up technique (k-t BLAST) in monitoring tumor motion for thoracic and abdominal radiotherapy and examine the potential trade-off between increased sparsification (to increase imaging speed) and the potential loss of "true" information due to greater reliance on a priori information. METHODS: Lung tumor motion trajectories in the superior-inferior direction, previously recorded from ten lung cancer patients, were replayed using a motion phantom module driven by an MRI-compatible motion platform. Eppendorf test tubes filled with water which serve as fiducial markers were placed in the phantom. The modeled rigid and deformable motions were collected in a coronal image slice using balanced fast field echo in conjunction with k-t BLAST. Root mean square (RMS) error was used as a metric of spatial accuracy as measured trajectories were compared to input data. The loss of spatial information was characterized for progressively increasing acceleration factor from 1 to 16; the resultant sampling frequency was increased approximately from 2.5 to 19 Hz when the principal direction of the motion was set along frequency encoding direction. In addition to the phantom study, respiration-induced tumor motions were captured from two patients (kidney tumor and lung tumor) at 13 Hz over 49 s to demonstrate the impact of high speed motion monitoring over multiple breathing cycles. For each subject, the authors compared the tumor centroid trajectory as well as the deformable motion during free breathing. RESULTS: In the rigid and deformable phantom studies, the RMS error of target tracking at the acquisition speed of 19 Hz was approximately 0.3 0.4 mm, which was smaller than the reconstructed pixel resolution of 0.67 mm. In the patient study, the dynamic 2D MRI enabled the monitoring of cycle-to-cycle respiratory variability present in the tumor position. It was seen that the range of centroid motion as well as the area covered due to target motion during each individual respiratory cycle was underestimated compared to the entire motion range observed over multiple breathing cycles. CONCLUSIONS: The authors' initial results demonstrate that sparse-sampling- and reconstruction-based dynamic MRI can be used to achieve adequate image acquisition speeds without significant information loss for the task of radiotherapy guidance. Such monitoring can yield spatial and temporal information superior to conventional offline and online motion capture methods used in thoracic and abdominal radiotherapy. PMID- 27277031 TI - Combination of voxel-based and projection-based methods in terms of convergence for CT reconstruction. AB - PURPOSE: Recent applications of iterative image reconstruction algorithms to multislice helical CT have shown that iterative reconstruction can significantly improve image quality and reduce artifacts. In this paper, the authors introduce a combination of two different algorithms with different convergence properties: ordered subsets separable paraboloidal surrogates (OS-SPS) and iterative coordinate descent (ICD). The first one updates image voxels simultaneously, slightly changing attenuation values iteration by iteration. The second algorithm updates image voxel by voxel, each time performing full forward and backward projections of the voxel. It has been shown that ICD converges better at high frequency areas and requires more iterations to reconstruct low-frequency components of the image. In contrast to ICD, SPS requires multiple iterations to reconstruct high-frequency areas. In this paper, the authors introduce an algorithm which leverages the benefits of both ICD and SPS. METHODS: The idea is to update the entire image with SPS, determine high-frequency components, and focus ICD computations on it using nonhomogeneous ICD update. RESULTS: The authors have successfully implemented OS-SPS, ICD, their hybrid approach, and few variations of ICD based on spatially nonuniform updates. CONCLUSIONS: The authors have examined the convergence of different algorithms and found that proposed algorithm converges better than OS-SPS, ICD, as well as various improved variants of ICD. PMID- 27277032 TI - MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas. AB - PURPOSE: Imaging biomarker research focuses on discovering relationships between radiological features and histological findings. In glioblastoma patients, methylation of the O(6)-methylguanine methyltransferase (MGMT) gene promoter is positively correlated with an increased effectiveness of current standard of care. In this paper, the authors investigate texture features as potential imaging biomarkers for capturing the MGMT methylation status of glioblastoma multiforme (GBM) tumors when combined with supervised classification schemes. METHODS: A retrospective study of 155 GBM patients with known MGMT methylation status was conducted. Co-occurrence and run length texture features were calculated, and both support vector machines (SVMs) and random forest classifiers were used to predict MGMT methylation status. RESULTS: The best classification system (an SVM-based classifier) had a maximum area under the receiver-operating characteristic (ROC) curve of 0.85 (95% CI: 0.78-0.91) using four texture features (correlation, energy, entropy, and local intensity) originating from the T2-weighted images, yielding at the optimal threshold of the ROC curve, a sensitivity of 0.803 and a specificity of 0.813. CONCLUSIONS: Results show that supervised machine learning of MRI texture features can predict MGMT methylation status in preoperative GBM tumors, thus providing a new noninvasive imaging biomarker. PMID- 27277033 TI - Dosimetric comparison of stopping power calibration with dual-energy CT and single-energy CT in proton therapy treatment planning. AB - PURPOSE: The accuracy of proton dose calculation is dependent on the ability to correctly characterize patient tissues with medical imaging. The most common method is to correlate computed tomography (CT) numbers obtained via single energy CT (SECT) with proton stopping power ratio (SPR). CT numbers, however, cannot discriminate between a change in mass density and change in chemical composition of patient tissues. This limitation can have consequences on SPR calibration accuracy. Dual-energy CT (DECT) is receiving increasing interest as an alternative imaging modality for proton therapy treatment planning due to its ability to discriminate between changes in patient density and chemical composition. In the current work we use a phantom of known composition to demonstrate the dosimetric advantages of proton therapy treatment planning with DECT over SECT. METHODS: A phantom of known composition was scanned with a clinical SECT radiotherapy CT-simulator. The phantom was rescanned at a lower X ray tube potential to generate a complimentary DECT image set. A set of reference materials similar in composition to the phantom was used to perform a stoichiometric calibration of SECT CT number to proton SPRs. The same set of reference materials was used to perform a DECT stoichiometric calibration based on effective atomic number. The known composition of the phantom was used to assess the accuracy of SPR calibration with SECT and DECT. Intensity modulated proton therapy (IMPT) treatment plans were generated with the SECT and DECT image sets to assess the dosimetric effect of the imaging modality. Isodose difference maps and root mean square (RMS) error calculations were used to assess dose calculation accuracy. RESULTS: SPR calculation accuracy was found to be superior, on average, with DECT relative to SECT. Maximum errors of 12.8% and 2.2% were found for SECT and DECT, respectively. Qualitative examination of dose difference maps clearly showed the dosimetric advantages of DECT imaging, compared to SECT imaging for IMPT dose calculation for the case investigated. Quantitatively, the maximum dose calculation error in the SECT plan was 7.8%, compared to a value of 1.4% in the DECT plan. When considering the high dose target region, the root mean square (RMS) error in dose calculation was 2.1% and 0.4% for SECT and DECT, respectively. CONCLUSIONS: DECT-based proton treatment planning in a commercial treatment planning system was successfully demonstrated for the first time. DECT is an attractive imaging modality for proton therapy treatment planning owing to its ability to characterize density and chemical composition of patient tissues. SECT and DECT scans of a phantom of known composition have been used to demonstrate the dosimetric advantages obtainable in proton therapy treatment planning with DECT over the current approach based on SECT. PMID- 27277034 TI - Grating-based x-ray differential phase contrast imaging with twin peaks in phase stepping curves-phase retrieval and dewrapping. AB - PURPOSE: X-ray differential phase contrast CT implemented with Talbot interferometry employs phase-stepping to extract information of x-ray attenuation, phase shift, and small-angle scattering. Since inaccuracy may exist in the absorption grating G2 due to an imperfect fabrication, the effective period of G2 can be as large as twice the nominal period, leading to a phenomenon of twin peaks that differ remarkably in their heights. In this work, the authors investigate how to retrieve and dewrap the phase signal from the phase-stepping curve (PSC) with the feature of twin peaks for x-ray phase contrast imaging. METHODS: Based on the paraxial Fresnel-Kirchhoff theory, the analytical formulae to characterize the phenomenon of twin peaks in the PSC are derived. Then an approach to dewrap the retrieved phase signal by jointly using the phases of the first- and second-order Fourier components is proposed. Through an experimental investigation using a prototype x-ray phase contrast imaging system implemented with Talbot interferometry, the authors evaluate and verify the derived analytic formulae and the proposed approach for phase retrieval and dewrapping. RESULTS: According to theoretical analysis, the twin-peak phenomenon in PSC is a consequence of combined effects, including the inaccuracy in absorption grating G2, mismatch between phase grating and x-ray source spectrum, and finite size of x-ray tube's focal spot. The proposed approach is experimentally evaluated by scanning a phantom consisting of organic materials and a lab mouse. The preliminary data show that compared to scanning G2 over only one single nominal period and correcting the measured phase signal with an intuitive phase dewrapping method that is being used in the field, stepping G2 over twice its nominal period and dewrapping the measured phase signal with the proposed approach can significantly improve the quality of x-ray differential phase contrast imaging in both radiograph and CT. CONCLUSIONS: Using the phase retrieval and dewrapping methods proposed to deal with the phenomenon of twin peaks in PSCs and phase wrapping, the performance of grating-based x-ray differential phase contrast radiography and CT can be significantly improved. PMID- 27277035 TI - Impact of errors in recorded compressed breast thickness measurements on volumetric density classification using volpara v1.5.0 software. AB - PURPOSE: Mammographic density has been demonstrated to predict breast cancer risk. It has been proposed that it could be used for stratifying screening pathways and recommending additional imaging. Volumetric density tools use the recorded compressed breast thickness (CBT) of the breast measured at the x-ray unit in their calculation; however, the accuracy of the recorded thickness can vary. The aim of this study was to investigate whether inaccuracies in recorded CBT impact upon volumetric density classification and to examine whether the current quality control (QC) standard is sufficient for assessing mammographic density. METHODS: Raw data from 52 digital screening mammograms were included in the study. For each image, the clinically recorded CBT was artificially increased and decreased in increments of 1 mm to simulate measurement error, until +/-15% from the recorded CBT was reached. New images were created for each 1 mm step in thickness resulting in a total of 974 images which then had volpara density grade (VDG) and volumetric density percentage assigned. RESULTS: A change in VDG was observed in 38.5% (n = 20) of mammograms when applying +/-15% error to the recorded CBT and 11.5% (n = 6) was within the QC standard prescribed error of +/ 5 mm. CONCLUSIONS: The current QC standard of +/-5 mm error in recorded CBT creates the potential for error in mammographic density measurement. This may lead to inaccurate classification of mammographic density. The current QC standard for assessing mammographic density should be reconsidered. PMID- 27277036 TI - Angular oversampling with temporally offset layers on multilayer detectors in computed tomography. AB - PURPOSE: Today's computed tomography (CT) scanners operate at an increasingly high rotation speed in order to reduce motion artifacts and to fulfill the requirements of dynamic acquisition, e.g., perfusion and cardiac imaging, with lower angular sampling rate as a consequence. In this paper, a simple method for obtaining angular oversampling when using multilayer detectors in continuous rotation CT is presented. METHODS: By introducing temporal offsets between the measurement periods of the different layers on a multilayer detector, the angular sampling rate can be increased by a factor equal to the number of layers on the detector. The increased angular sampling rate reduces the risk of producing aliasing artifacts in the image. A simulation of a detector with two layers is performed to prove the concept. RESULTS: The simulation study shows that aliasing artifacts from insufficient angular sampling are reduced by the proposed method. Specifically, when imaging a single point blurred by a 2D Gaussian kernel, the method is shown to reduce the strength of the aliasing artifacts by approximately an order of magnitude. CONCLUSIONS: The presented oversampling method is easy to implement in today's multilayer detectors and has the potential to reduce aliasing artifacts in the reconstructed images. PMID- 27277038 TI - Validation of Varian TrueBeam electron phase-spaces for Monte Carlo simulation of MLC-shaped fields. AB - PURPOSE: This work evaluates Varian's electron phase-space sources for Monte Carlo simulation of the TrueBeam for modulated electron radiation therapy (MERT) and combined, modulated photon and electron radiation therapy (MPERT) where fields are shaped by the photon multileaf collimator (MLC) and delivered at 70 cm SSD. METHODS: Monte Carlo simulations performed with EGSnrc-based BEAMnrc/DOSXYZnrc and penelope-based PRIMO are compared against diode measurements for 5 * 5, 10 * 10, and 20 * 20 cm(2) MLC-shaped fields delivered with 6, 12, and 20 MeV electrons at 70 cm SSD (jaws set to 40 * 40 cm(2)). Depth dose curves and profiles are examined. In addition, EGSnrc-based simulations of relative output as a function of MLC-field size and jaw-position are compared against ion chamber measurements for MLC-shaped fields between 3 * 3 and 25 * 25 cm(2) and jaw positions that range from the MLC-field size to 40 * 40 cm(2). RESULTS: Percent depth dose curves generated by BEAMnrc/DOSXYZnrc and PRIMO agree with measurement within 2%, 2 mm except for PRIMO's 12 MeV, 20 * 20 cm(2) field where 90% of dose points agree within 2%, 2 mm. Without the distance to agreement, differences between measurement and simulation are as large as 7.3%. Characterization of simulated dose parameters such as FWHM, penumbra width and depths of 90%, 80%, 50%, and 20% dose agree within 2 mm of measurement for all fields except for the FWHM of the 6 MeV, 20 * 20 cm(2) field which falls within 2 mm distance to agreement. Differences between simulation and measurement exist in the profile shoulders and penumbra tails, in particular for 10 * 10 and 20 * 20 cm(2) fields of 20 MeV electrons, where both sets of simulated data fall short of measurement by as much as 3.5%. BEAMnrc/DOSXYZnrc simulated outputs agree with measurement within 2.3% except for 6 MeV MLC-shaped fields. Discrepancies here are as great as 5.5%. CONCLUSIONS: TrueBeam electron phase-spaces available from Varian have been implemented in two distinct Monte Carlo simulation packages to produce dose distributions and outputs that largely reflect measurement. Differences exist in the profile shoulders and penumbra tails for the 20 MeV phase-space off-axis and in the outputs for the 6 MeV phase-space. PMID- 27277037 TI - Geometry planning and image registration in magnetic particle imaging using bimodal fiducial markers. AB - PURPOSE: Magnetic particle imaging (MPI) is a quantitative imaging modality that allows the distribution of superparamagnetic nanoparticles to be visualized. Compared to other imaging techniques like x-ray radiography, computed tomography (CT), and magnetic resonance imaging (MRI), MPI only provides a signal from the administered tracer, but no additional morphological information, which complicates geometry planning and the interpretation of MP images. The purpose of the authors' study was to develop bimodal fiducial markers that can be visualized by MPI and MRI in order to create MP-MR fusion images. METHODS: A certain arrangement of three bimodal fiducial markers was developed and used in a combined MRI/MPI phantom and also during in vivo experiments in order to investigate its suitability for geometry planning and image fusion. An algorithm for automated marker extraction in both MR and MP images and rigid registration was established. RESULTS: The developed bimodal fiducial markers can be visualized by MRI and MPI and allow for geometry planning as well as automated registration and fusion of MR-MP images. CONCLUSIONS: To date, exact positioning of the object to be imaged within the field of view (FOV) and the assignment of reconstructed MPI signals to corresponding morphological regions has been difficult. The developed bimodal fiducial markers and the automated image registration algorithm help to overcome these difficulties. PMID- 27277039 TI - Minimizing treatment planning errors in proton therapy using failure mode and effects analysis. AB - PURPOSE: Failure mode and effects analysis (FMEA) is a widely used tool to evaluate safety or reliability in conventional photon radiation therapy. However, reports about FMEA application in proton therapy are scarce. The purpose of this study is to apply FMEA in safety improvement of proton treatment planning at their center. METHODS: The authors performed an FMEA analysis of their proton therapy treatment planning process using uniform scanning proton beams. The authors identified possible failure modes in various planning processes, including image fusion, contouring, beam arrangement, dose calculation, plan export, documents, billing, and so on. For each error, the authors estimated the frequency of occurrence, the likelihood of being undetected, and the severity of the error if it went undetected and calculated the risk priority number (RPN). The FMEA results were used to design their quality management program. In addition, the authors created a database to track the identified dosimetric errors. Periodically, the authors reevaluated the risk of errors by reviewing the internal error database and improved their quality assurance program as needed. RESULTS: In total, the authors identified over 36 possible treatment planning related failure modes and estimated the associated occurrence, detectability, and severity to calculate the overall risk priority number. Based on the FMEA, the authors implemented various safety improvement procedures into their practice, such as education, peer review, and automatic check tools. The ongoing error tracking database provided realistic data on the frequency of occurrence with which to reevaluate the RPNs for various failure modes. CONCLUSIONS: The FMEA technique provides a systematic method for identifying and evaluating potential errors in proton treatment planning before they result in an error in patient dose delivery. The application of FMEA framework and the implementation of an ongoing error tracking system at their clinic have proven to be useful in error reduction in proton treatment planning, thus improving the effectiveness and safety of proton therapy. PMID- 27277040 TI - Anatomical pulmonary magnetic resonance imaging segmentation for regional structure-function measurements of asthma. AB - PURPOSE: Pulmonary magnetic-resonance-imaging (MRI) and x-ray computed-tomography have provided strong evidence of spatially and temporally persistent lung structure-function abnormalities in asthmatics. This has generated a shift in their understanding of lung disease and supports the use of imaging biomarkers as intermediate endpoints of asthma severity and control. In particular, pulmonary (1)H MRI can be used to provide quantitative lung structure-function measurements longitudinally and in response to treatment. However, to translate such biomarkers of asthma, robust methods are required to segment the lung from pulmonary (1)H MRI. Therefore, their objective was to develop a pulmonary (1)H MRI segmentation algorithm to provide regional measurements with the precision and speed required to support clinical studies. METHODS: The authors developed a method to segment the left and right lung from (1)H MRI acquired in 20 asthmatics including five well-controlled and 15 severe poorly controlled participants who provided written informed consent to a study protocol approved by Health Canada. Same-day spirometry and plethysmography measurements of lung function and volume were acquired as well as (1)H MRI using a whole-body radiofrequency coil and fast spoiled gradient-recalled echo sequence at a fixed lung volume (functional residual capacity + 1 l). We incorporated the left-to-right lung volume proportion prior based on the Potts model and derived a volume-proportion preserved Potts model, which was approximated through convex relaxation and further represented by a dual volume-proportion preserved max-flow model. The max flow model led to a linear problem with convex and linear equality constraints that implicitly encoded the proportion prior. To implement the algorithm, (1)H MRI was resampled into ~3 * 3 * 3 mm(3) isotropic voxel space. Two observers placed seeds on each lung and on the background of 20 pulmonary (1)H MR images in a randomized dataset, on five occasions, five consecutive days in a row. Segmentation accuracy was evaluated using the Dice-similarity-coefficient (DSC) of the segmented thoracic cavity with comparison to five-rounds of manual segmentation by an expert observer. The authors also evaluated the root-mean squared-error (RMSE) of the Euclidean distance between lung surfaces, the absolute, and percent volume error. Reproducibility was measured using the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for two observers who repeated segmentation measurements five-times. RESULTS: For five well-controlled asthmatics, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) was 83% +/- 7% and FEV1 was 86 +/- 9%pred. For 15 severe, poorly controlled asthmatics, FEV1/FV C = 66% +/- 17% and FEV1 = 72 +/- 27%pred. The DSC for algorithm and manual segmentation was 91% +/- 3%, 92% +/- 2% and 91% +/- 2% for the left, right, and whole lung, respectively. RMSE was 4.0 +/- 1.0 mm for each of the left, right, and whole lung. The absolute (percent) volume errors were 0.1 l (~6%) for each of right and left lung and ~0.2 l (~6%) for whole lung. Intra- and inter-CoV (ICC) were <0.5% (>0.91%) for DSC and <4.5% (>0.93%) for RMSE. While segmentation required 10 s including ~6 s for user interaction, the smallest detectable difference was 0.24 l for algorithm measurements which was similar to manual measurements. CONCLUSIONS: This lung segmentation approach provided the necessary and sufficient precision and accuracy required for research and clinical studies. PMID- 27277041 TI - Technical Note: Enhancing the surface dose using a weak longitudinal magnetic field. AB - PURPOSE: The surface dose in radiotherapy is subject to the physical properties of the radiation beam and collimator. The purpose of this work is to investigate the manipulation of surface dose using magnetic fields produced with a resistive magnet. Better understanding of the feasibility and mechanisms of altered surface dose could have important clinical applications where the surface dose must be increased for therapeutic goals, or reduced to enhance the therapeutic benefit. METHODS: A resistive magnet capable of generating a peak magnetic field up to 0.24 T was integrated with a cobalt treatment unit. The magnetic fringe field of the magnet was small due to the self-shielding built within the magnet. The magnetic field at the beam collimation jaws of the cobalt irradiator was less than 10 G. The surface dose and depth dose were measured for varying magnetic field strengths. RESULTS: The resistive magnet was able to alter the dose in the buildup region of the (60)Co depth dose significantly, and the magnitude of dose enhancement was directly related to the strength of the longitudinal magnetic field. Peak magnetic fields as low as 0.08 T were able to affect the surface dose. At a peak field of 0.24 T, the authors measured a surface dose enhancement of 2.8-fold. CONCLUSIONS: Surface dose enhancement using resistive magnets is feasible. Further experimental study is needed to understand the origin of the scattered electrons that contribute to the increase in surface dose. PMID- 27277042 TI - A clinically observed discrepancy between image-based and log-based MLC positions. AB - PURPOSE: To present a clinical case in which real-time intratreatment imaging identified an multileaf collimator (MLC) leaf to be consistently deviating from its programmed and logged position by >1 mm. METHODS: An EPID-based exit-fluence dosimetry system designed to prevent gross delivery errors was used to capture cine during treatment images. The author serendipitously visually identified a suspected MLC leaf displacement that was not otherwise detected. The leaf position as recorded on the EPID images was measured and log-files were analyzed for the treatment in question, the prior day's treatment, and for daily MLC test patterns acquired on those treatment days. Additional standard test patterns were used to quantify the leaf position. RESULTS: Whereas the log-file reported no difference between planned and recorded positions, image-based measurements showed the leaf to be 1.3 +/- 0.1 mm medial from the planned position. This offset was confirmed with the test pattern irradiations. CONCLUSIONS: It has been clinically observed that log-file derived leaf positions can differ from their actual position by >1 mm, and therefore cannot be considered to be the actual leaf positions. This cautions the use of log-based methods for MLC or patient quality assurance without independent confirmation of log integrity. Frequent verification of MLC positions through independent means is a necessary precondition to trust log-file records. Intratreatment EPID imaging provides a method to capture departures from MLC planned positions. PMID- 27277043 TI - Spatial intratumoral heterogeneity of proliferation in immunohistochemical images of solid tumors. AB - PURPOSE: The interactions of neoplastic cells with each other and the microenvironment are complex. To understand intratumoral heterogeneity, subtle differences should be quantified. Main factors contributing to heterogeneity include the gradient ischemic level within neoplasms, action of microenvironment, mechanisms of intercellular transfer of genetic information, and differential mechanisms of modifications of genetic material/proteins. This may reflect on the expression of biomarkers in the context of prognosis/stratification. Hence, a rigorous approach for assessing the spatial intratumoral heterogeneity of histological biomarker expression with accuracy and reproducibility is required, since patterns in immunohistochemical images can be challenging to identify and describe. METHODS: A quantitative method that is useful for characterizing complex irregular structures is lacunarity; it is a multiscale technique that exhaustively samples the image, while the decay of its index as a function of window size follows characteristic patterns for different spatial arrangements. In histological images, lacunarity provides a useful measure for the spatial organization of a biomarker when a sampling scheme is employed and relevant features are computed. The proposed approach quantifies the segmented proliferative cells and not the textural content of the histological slide, thus providing a more realistic measure of heterogeneity within the sample space of the tumor region. The aim is to investigate in whole sections of primary pancreatic neuroendocrine neoplasms (pNENs), using whole-slide imaging and image analysis, the spatial intratumoral heterogeneity of Ki-67 immunostains. Unsupervised learning is employed to verify that the approach can partition the tissue sections according to distributional heterogeneity. RESULTS: The architectural complexity of histological images has shown that single measurements are often insufficient. Inhomogeneity of distribution depends not only on percentage content of proliferation phase but also on how the phase fills the space. Lacunarity curves demonstrate variations in the sampled image sections. Since the spatial distribution of proliferation in each case is different, the width of the curves changes too. Image sections that have smaller numerical variations in the computed features correspond to neoplasms with spatially homogeneous proliferation, while larger variations correspond to cases where proliferation shows various degrees of clumping. Grade 1 (uniform/nonuniform: 74%/26%) and grade 3 (uniform: 100%) pNENs demonstrate a more homogeneous proliferation with grade 1 neoplasms being more variant, while grade 2 tumor regions render a more diverse landscape (50%/50%). Hence, some cases show an increased degree of spatial heterogeneity comparing to others with similar grade. Whether this is a sign of different tumor biology and an association with a more benign/malignant clinical course needs to be investigated further. The extent and range of spatial heterogeneity has the potential to be evaluated as a prognostic marker. CONCLUSIONS: The association with tumor grade as well as the rationale that the methodology reflects true tumor architecture supports the technical soundness of the method. This reflects a general approach which is relevant to other solid tumors and biomarkers. Drawing upon the merits of computational biomedicine, the approach uncovers salient features for use in future studies of clinical relevance. PMID- 27277044 TI - Semiautomated segmentation of head and neck cancers in 18F-FDG PET scans: A just enough-interaction approach. AB - PURPOSE: The purpose of this work was to develop, validate, and compare a highly computer-aided method for the segmentation of hot lesions in head and neck 18F FDG PET scans. METHODS: A semiautomated segmentation method was developed, which transforms the segmentation problem into a graph-based optimization problem. For this purpose, a graph structure around a user-provided approximate lesion centerpoint is constructed and a suitable cost function is derived based on local image statistics. To handle frequently occurring situations that are ambiguous (e.g., lesions adjacent to each other versus lesion with inhomogeneous uptake), several segmentation modes are introduced that adapt the behavior of the base algorithm accordingly. In addition, the authors present approaches for the efficient interactive local and global refinement of initial segmentations that are based on the "just-enough-interaction" principle. For method validation, 60 PET/CT scans from 59 different subjects with 230 head and neck lesions were utilized. All patients had squamous cell carcinoma of the head and neck. A detailed comparison with the current clinically relevant standard manual segmentation approach was performed based on 2760 segmentations produced by three experts. RESULTS: Segmentation accuracy measured by the Dice coefficient of the proposed semiautomated and standard manual segmentation approach was 0.766 and 0.764, respectively. This difference was not statistically significant (p = 0.2145). However, the intra- and interoperator standard deviations were significantly lower for the semiautomated method. In addition, the proposed method was found to be significantly faster and resulted in significantly higher intra- and interoperator segmentation agreement when compared to the manual segmentation approach. CONCLUSIONS: Lack of consistency in tumor definition is a critical barrier for radiation treatment targeting as well as for response assessment in clinical trials and in clinical oncology decision-making. The properties of the authors approach make it well suited for applications in image guided radiation oncology, response assessment, or treatment outcome prediction. PMID- 27277045 TI - A Monte Carlo study on (223)Ra imaging for unsealed radionuclide therapy. AB - PURPOSE: Radium-223 ((223)Ra), an alpha-emitting radionuclide, is used in unsealed radionuclide therapy for metastatic bone tumors. The demand for qualitative (223)Ra imaging is growing to optimize dosimetry. The authors simulated (223)Ra imaging using an in-house Monte Carlo simulation code and investigated the feasibility and utility of (223)Ra imaging. METHODS: The Monte Carlo code comprises two modules, hexagon and nai. The hexagon code simulates the photon and electron interactions in the tissues and collimator, and the nai code simulates the response of the NaI detector system. A 3D numeric phantom created using computed tomography images of a chest phantom was installed in the hexagon code. (223)Ra accumulated in a part of the spine, and three x-rays and 19 gamma rays between 80 and 450 keV were selected as the emitted photons. To evaluate the quality of the (223)Ra imaging, the authors also simulated technetium-99m ((99m)Tc) imaging under the same conditions and compared the results. RESULTS: The sensitivities of the three photopeaks were 147 counts per unit of source activity (cps MBq(-1); photopeak: 84 keV, full width of energy window: 20%), 166 cps MBq(-1) (154 keV, 15%), and 158 cps MBq(-1) (270 keV, 10%) for a low-energy general-purpose (LEGP) collimator, and those for the medium-energy general purpose (MEGP) collimator were 33, 13, and 8.0 cps MBq(-1), respectively. In the case of (99m)Tc, the sensitivity was 55 cps MBq(-1) (141 keV, 20%) for LEGP and 52 cps MBq(-1) for MEGP. The fractions of unscattered photons of the total photons reflecting the image quality were 0.09 (84 keV), 0.03 (154 keV), and 0.02 (270 keV) for the LEGP collimator and 0.41, 0.25, and 0.50 for the MEGP collimator, respectively. Conversely, this fraction was approximately 0.65 for the simulated (99m)Tc imaging. The sensitivity with the LEGP collimator appeared very high. However, almost all of the counts were because of photons that penetrated or were scattered in the collimator; therefore, the proportions of unscattered photons were small. CONCLUSIONS: Their simulation study revealed that the most promising scheme for (223)Ra imaging is an 84-keV window using an MEGP collimator. The sensitivity of the photopeaks above 100 keV is too low for (223)Ra imaging. A comparison of the fractions of unscattered photons reveals that the sensitivity and image quality are approximately two-thirds of those for (99m)Tc imaging. PMID- 27277046 TI - A region-based segmentation method for ultrasound images in HIFU therapy. AB - PURPOSE: Precisely and efficiently locating a tumor with less manual intervention in ultrasound-guided high-intensity focused ultrasound (HIFU) therapy is one of the keys to guaranteeing the therapeutic result and improving the efficiency of the treatment. The segmentation of ultrasound images has always been difficult due to the influences of speckle, acoustic shadows, and signal attenuation as well as the variety of tumor appearance. The quality of HIFU guidance images is even poorer than that of conventional diagnostic ultrasound images because the ultrasonic probe used for HIFU guidance usually obtains images without making contact with the patient's body. Therefore, the segmentation becomes more difficult. To solve the segmentation problem of ultrasound guidance image in the treatment planning procedure for HIFU therapy, a novel region-based segmentation method for uterine fibroids in HIFU guidance images is proposed. METHODS: Tumor partitioning in HIFU guidance image without manual intervention is achieved by a region-based split-and-merge framework. A new iterative multiple region growing algorithm is proposed to first split the image into homogenous regions (superpixels). The features extracted within these homogenous regions will be more stable than those extracted within the conventional neighborhood of a pixel. The split regions are then merged by a superpixel-based adaptive spectral clustering algorithm. To ensure the superpixels that belong to the same tumor can be clustered together in the merging process, a particular construction strategy for the similarity matrix is adopted for the spectral clustering, and the similarity matrix is constructed by taking advantage of a combination of specifically selected first-order and second-order texture features computed from the gray levels and the gray level co-occurrence matrixes, respectively. The tumor region is picked out automatically from the background regions by an algorithm according to a priori information about the tumor position, shape, and size. Additionally, an appropriate cluster number for spectral clustering can be determined by the same algorithm, thus the automatic segmentation of the tumor region is achieved. RESULTS: To evaluate the performance of the proposed method, 50 uterine fibroid ultrasound images from different patients receiving HIFU therapy were segmented, and the obtained tumor contours were compared with those delineated by an experienced radiologist. For area-based evaluation results, the mean values of the true positive ratio, the false positive ratio, and the similarity were 94.42%, 4.71%, and 90.21%, respectively, and the corresponding standard deviations were 2.54%, 3.12%, and 3.50%, respectively. For distance based evaluation results, the mean values of the normalized Hausdorff distance and the normalized mean absolute distance were 4.93% and 0.90%, respectively, and the corresponding standard deviations were 2.22% and 0.34%, respectively. The running time of the segmentation process was 12.9 s for a 318 * 333 (pixels) image. CONCLUSIONS: Experiments show that the proposed method can segment the tumor region accurately and efficiently with less manual intervention, which provides for the possibility of automatic segmentation and real-time guidance in HIFU therapy. PMID- 27277047 TI - Data and methods to estimate fetal dose from fluoroscopically guided prophylactic hypogastric artery balloon occlusion. AB - PURPOSE: To provide data for estimation of fetal radiation dose (DF) from prophylactic hypogastric artery balloon occlusion (HABO) procedures. METHODS: The Monte-Carlo-N-particle (MCNP) transport code and mathematical phantoms representing a pregnant patient at the ninth month of gestation were employed. PA, RAO 20 degrees and LAO 20 degrees fluoroscopy projections of left and right internal iliac arteries were simulated. Projection-specific normalized fetal dose (NFD) data were produced for various beam qualities. The effects of projection angle, x-ray field location relative to the fetus, field size, maternal body size, and fetal size on NFD were investigated. Presented NFD values were compared to corresponding values derived using a physical anthropomorphic phantom simulating pregnancy at the third trimester and thermoluminescence dosimeters. RESULTS: NFD did not considerably vary when projection angle was altered by +/-5 degrees , whereas it was found to markedly depend on tube voltage, filtration, x ray field location and size, and maternal body size. Differences in NFD < 7.5% were observed for naturally expected variations in fetal size. A difference of less than 13.5% was observed between NFD values estimated by MCNP and direct measurements. CONCLUSIONS: Data and methods provided allow for reliable estimation of radiation burden to the fetus from HABO. PMID- 27277048 TI - Development of a temperature-controlled phantom for magnetic resonance quality assurance of diffusion, dynamic, and relaxometry measurements. AB - PURPOSE: Diffusion-weighted (DW) and dynamic contrast-enhanced magnetic resonance imaging (MRI) are increasingly applied for the assessment of functional tissue biomarkers for diagnosis, lesion characterization, or for monitoring of treatment response. However, these techniques are vulnerable to the influence of various factors, so there is a necessity for a standardized MR quality assurance procedure utilizing a phantom to facilitate the reliable estimation of repeatability of these quantitative biomarkers arising from technical factors (e.g., B1 variation) affecting acquisition on scanners of different vendors and field strengths. The purpose of this study is to present a novel phantom designed for use in quality assurance for multicenter trials, and the associated repeatability measurements of functional and quantitative imaging protocols across different MR vendors and field strengths. METHODS: A cylindrical acrylic phantom was manufactured containing 7 vials of polyvinylpyrrolidone (PVP) solutions of different concentrations, ranging from 0% (distilled water) to 25% w/w, to create a range of different MR contrast parameters. Temperature control was achieved by equilibration with ice-water. Repeated MR imaging measurements of the phantom were performed on four clinical scanners (two at 1.5 T, two at 3.0 T; two vendors) using the same scanning protocol to assess the long-term and short term repeatability. The scanning protocol consisted of DW measurements, inversion recovery (IR) T1 measurements, multiecho T2 measurement, and dynamic T1-weighted sequence allowing multiple variable flip angle (VFA) estimation of T1 values over time. For each measurement, the corresponding calculated parameter maps were produced. On each calculated map, regions of interest (ROIs) were drawn within each vial and the median value of these voxels was assessed. For the dynamic data, the autocorrelation function and their variance were calculated; for the assessment of the repeatability, the coefficients of variation (CoV) were calculated. RESULTS: For both field strengths across the available vendors, the apparent diffusion coefficient (ADC) at 0 degrees C ranged from (1.12 +/- 0.01) * 10(-3) mm(2)/s for pure water to (0.48 +/- 0.02) * 10(-3) mm(2)/s for the 25% w/w PVP concentration, presenting a minor variability between the vendors and the field strengths. T2 and IR-T1 relaxation time results demonstrated variability between the field strengths and the vendors across the different acquisitions. Moreover, the T1 values derived from the VFA method exhibited a large variation compared with the IR-T1 values across all the scanners for all repeated measurements, although the calculation of the standard deviation of the VFA-T1 estimate across each ROI and the autocorrelation showed a stability of the signal for three scanners, with autocorrelation of the signal over the dynamic series revealing a periodic variation in one scanner. Finally, the ADC, the T2, and the IR-T1 values exhibited an excellent repeatability across the scanners, whereas for the dynamic data, the CoVs were higher. CONCLUSIONS: The combination of a novel PVP phantom, with multiple compartments to give a physiologically relevant range of ADC and T1 values, together with ice-water as a temperature-controlled medium, allows reliable quality assurance measurements that can be used to measure agreement between MRI scanners, critical in multicenter functional and quantitative imaging studies. PMID- 27277049 TI - Source strength verification and quality assurance of preloaded brachytherapy needles using a CMOS flat panel detector. AB - PURPOSE: Current methods of low dose rate brachytherapy source strength verification for sources preloaded into needles consist of either assaying a small number of seeds from a separate sample belonging to the same lot used to load the needles or performing batch assays of a subset of the preloaded seed trains. Both of these methods are cumbersome and have the limitations inherent to sampling. The purpose of this work was to investigate an alternative approach that uses an image-based, autoradiographic system capable of the rapid and complete assay of all sources without compromising sterility. METHODS: The system consists of a flat panel image detector, an autoclavable needle holder, and software to analyze the detected signals. The needle holder was designed to maintain a fixed vertical spacing between the needles and the image detector, and to collimate the emissions from each seed. It also provides a sterile barrier between the needles and the imager. The image detector has a sufficiently large image capture area to allow several needles to be analyzed simultaneously.Several tests were performed to assess the accuracy and reproducibility of source strengths obtained using this system. Three different seed models (Oncura 6711 and 9011 (125)I seeds, and IsoAid Advantage (103)Pd seeds) were used in the evaluations. Seeds were loaded into trains with at least 1 cm spacing. RESULTS: Using our system, it was possible to obtain linear calibration curves with coverage factor k = 1 prediction intervals of less than +/-2% near the centre of their range for the three source models. The uncertainty budget calculated from a combination of type A and type B estimates of potential sources of error was somewhat larger, yielding (k = 1) combined uncertainties for individual seed readings of 6.2% for (125)I 6711 seeds, 4.7% for (125)I 9011 seeds, and 11.0% for Advantage (103)Pd seeds. CONCLUSIONS: This study showed that a flat panel detector dosimetry system is a viable option for source strength verification in preloaded needles, as it is capable of measuring all of the sources intended for implantation. Such a system has the potential to directly and efficiently estimate individual source strengths, the overall mean source strength, and the positions within the seed-spacer train. PMID- 27277050 TI - Iterative metal artifact reduction for x-ray computed tomography using unmatched projector/backprojector pairs. AB - PURPOSE: Metal artifact reduction (MAR) is a major problem and a challenging issue in x-ray computed tomography (CT) examinations. Iterative reconstruction from sinograms unaffected by metals shows promising potential in detail recovery. This reconstruction has been the subject of much research in recent years. However, conventional iterative reconstruction methods easily introduce new artifacts around metal implants because of incomplete data reconstruction and inconsistencies in practical data acquisition. Hence, this work aims at developing a method to suppress newly introduced artifacts and improve the image quality around metal implants for the iterative MAR scheme. METHODS: The proposed method consists of two steps based on the general iterative MAR framework. An uncorrected image is initially reconstructed, and the corresponding metal trace is obtained. The iterative reconstruction method is then used to reconstruct images from the unaffected sinogram. In the reconstruction step of this work, an iterative strategy utilizing unmatched projector/backprojector pairs is used. A ramp filter is introduced into the back-projection procedure to restrain the inconsistency components in low frequencies and generate more reliable images of the regions around metals. Furthermore, a constrained total variation (TV) minimization model is also incorporated to enhance efficiency. The proposed strategy is implemented based on an iterative FBP and an alternating direction minimization (ADM) scheme, respectively. The developed algorithms are referred to as "iFBP-TV" and "TV-FADM," respectively. Two projection-completion-based MAR methods and three iterative MAR methods are performed simultaneously for comparison. RESULTS: The proposed method performs reasonably on both simulation and real CT-scanned datasets. This approach could reduce streak metal artifacts effectively and avoid the mentioned effects in the vicinity of the metals. The improvements are evaluated by inspecting regions of interest and by comparing the root-mean-square errors, normalized mean absolute distance, and universal quality index metrics of the images. Both iFBP-TV and TV-FADM methods outperform other counterparts in all cases. Unlike the conventional iterative methods, the proposed strategy utilizing unmatched projector/backprojector pairs shows excellent performance in detail preservation and prevention of the introduction of new artifacts. CONCLUSIONS: Qualitative and quantitative evaluations of experimental results indicate that the developed method outperforms classical MAR algorithms in suppressing streak artifacts and preserving the edge structural information of the object. In particular, structures lying close to metals can be gradually recovered because of the reduction of artifacts caused by inconsistency effects. PMID- 27277051 TI - Concurrent Monte Carlo transport and fluence optimization with fluence adjusting scalable transport Monte Carlo. AB - PURPOSE: The future of radiation therapy will require advanced inverse planning solutions to support single-arc, multiple-arc, and "4pi" delivery modes, which present unique challenges in finding an optimal treatment plan over a vast search space, while still preserving dosimetric accuracy. The successful clinical implementation of such methods would benefit from Monte Carlo (MC) based dose calculation methods, which can offer improvements in dosimetric accuracy when compared to deterministic methods. The standard method for MC based treatment planning optimization leverages the accuracy of the MC dose calculation and efficiency of well-developed optimization methods, by precalculating the fluence to dose relationship within a patient with MC methods and subsequently optimizing the fluence weights. However, the sequential nature of this implementation is computationally time consuming and memory intensive. Methods to reduce the overhead of the MC precalculation have been explored in the past, demonstrating promising reductions of computational time overhead, but with limited impact on the memory overhead due to the sequential nature of the dose calculation and fluence optimization. The authors propose an entirely new form of "concurrent" Monte Carlo treat plan optimization: a platform which optimizes the fluence during the dose calculation, reduces wasted computation time being spent on beamlets that weakly contribute to the final dose distribution, and requires only a low memory footprint to function. In this initial investigation, the authors explore the key theoretical and practical considerations of optimizing fluence in such a manner. METHODS: The authors present a novel derivation and implementation of a gradient descent algorithm that allows for optimization during MC particle transport, based on highly stochastic information generated through particle transport of very few histories. A gradient rescaling and renormalization algorithm, and the concept of momentum from stochastic gradient descent were used to address obstacles unique to performing gradient descent fluence optimization during MC particle transport. The authors have applied their method to two simple geometrical phantoms, and one clinical patient geometry to examine the capability of this platform to generate conformal plans as well as assess its computational scaling and efficiency, respectively. RESULTS: The authors obtain a reduction of at least 50% in total histories transported in their investigation compared to a theoretical unweighted beamlet calculation and subsequent fluence optimization method, and observe a roughly fixed optimization time overhead consisting of ~10% of the total computation time in all cases. Finally, the authors demonstrate a negligible increase in memory overhead of ~7-8 MB to allow for optimization of a clinical patient geometry surrounded by 36 beams using their platform. CONCLUSIONS: This study demonstrates a fluence optimization approach, which could significantly improve the development of next generation radiation therapy solutions while incurring minimal additional computational overhead. PMID- 27277052 TI - Maximum likelihood positioning algorithm for high-resolution PET scanners. AB - PURPOSE: In high-resolution positron emission tomography (PET), lightsharing elements are incorporated into typical detector stacks to read out scintillator arrays in which one scintillator element (crystal) is smaller than the size of the readout channel. In order to identify the hit crystal by means of the measured light distribution, a positioning algorithm is required. One commonly applied positioning algorithm uses the center of gravity (COG) of the measured light distribution. The COG algorithm is limited in spatial resolution by noise and intercrystal Compton scatter. The purpose of this work is to develop a positioning algorithm which overcomes this limitation. METHODS: The authors present a maximum likelihood (ML) algorithm which compares a set of expected light distributions given by probability density functions (PDFs) with the measured light distribution. Instead of modeling the PDFs by using an analytical model, the PDFs of the proposed ML algorithm are generated assuming a single gamma-interaction model from measured data. The algorithm was evaluated with a hot-rod phantom measurement acquired with the preclinical hyperion II (D) PET scanner. In order to assess the performance with respect to sensitivity, energy resolution, and image quality, the ML algorithm was compared to a COG algorithm which calculates the COG from a restricted set of channels. The authors studied the energy resolution of the ML and the COG algorithm regarding incomplete light distributions (missing channel information caused by detector dead time). Furthermore, the authors investigated the effects of using a filter based on the likelihood values on sensitivity, energy resolution, and image quality. RESULTS: A sensitivity gain of up to 19% was demonstrated in comparison to the COG algorithm for the selected operation parameters. Energy resolution and image quality were on a similar level for both algorithms. Additionally, the authors demonstrated that the performance of the ML algorithm is less prone to missing channel information. A likelihood filter visually improved the image quality, i.e., the peak-to-valley increased up to a factor of 3 for 2-mm-diameter phantom rods by rejecting 87% of the coincidences. A relative improvement of the energy resolution of up to 12.8% was also measured rejecting 91% of the coincidences. CONCLUSIONS: The developed ML algorithm increases the sensitivity by correctly handling missing channel information without influencing energy resolution or image quality. Furthermore, the authors showed that energy resolution and image quality can be improved substantially by rejecting events that do not comply well with the single-gamma-interaction model, such as Compton-scattered events. PMID- 27277053 TI - Performance characteristics of dedicated molecular breast imaging systems at low doses. AB - PURPOSE: The purpose of this study was to compare the system performance characteristics and lesion detection capability of two molecular breast imaging (MBI) systems: a multicrystal sodium iodide (NaI)-based single-head system and a cadmium zinc telluride (CZT)-based dual-head system at low administered doses (150-300 MBq) of Tc-99m sestamibi. METHODS: System performance characteristics including count sensitivity, uniformity, energy resolution, and spatial resolution were measured using standard NEMA methods, or a modified version thereof in cases where the standard NEMA protocol could not be applied. A contrast-detail phantom with 48 lesions at varying depths from the collimator surface was used to assess lesion contrast-to-noise-ratio (CNR) using background count densities comparable to those observed in patient studies performed with administered doses of 150 MBq Tc-99m sestamibi. Lesions with CNR >3 were deemed to be detectable. Thirty patients undergoing MBI examinations with administered doses of 150-300 MBq were scanned for an additional view on the pixelated NaI system. CNR was calculated for lesions observed on patient images. Background count densities of patient images were measured and compared between the two systems. RESULTS: Over the central field of view, integral and differential uniformity were 6.1% and 4.2%, respectively, for the pixelated NaI system, and 3.8% and 2.7%, respectively, for the CZT system. Count sensitivity was 10.8 kcts/min/MBq for the NaI system and 32.9 kcts/min/MBq for the CZT system. Energy resolution was 13.5% on the pixelated NaI system and 4.5% on the CZT system. Spatial resolution (full-width at half-maximum) for the pixelated NaI detector was 4.2 mm at a distance of 1.2 cm from the collimator and 5.2 mm at 3.1 cm. Spatial resolution of a single CZT detector was 2.9 mm at a distance of 1.2 cm from the collimator and 4.7 mm at 3.1 cm. Effective spatial resolution obtained with dual-head CZT was below 4.7 mm throughout a simulated breast thickness of 6 cm. From contrast-detail phantom images of lesions at distances of 1.5-4.5 cm from the collimator face, the CZT system detected 124 of 144 (86%) of lesions compared to 97 of 144 (67%) with the NaI system. In patient studies, from comparison of the same view with both systems, a total of 7 breast lesions were identified on CZT system in seven patients, and 4 of 7 (57%) were detected on NaI system. Patient image background count densities on the CZT system were on average 3.4 times higher than those on the NaI system. CONCLUSIONS: The CZT system demonstrated better uniformity, count sensitivity, spatial resolution, energy resolution, and lesion detection in phantom and patient studies compared to the NaI system. At administered doses of 150-300 MBq Tc-99m sestamibi, patient results obtained with CZT systems may not be directly translatable to NaI systems. PMID- 27277054 TI - Estimation of trabecular bone parameters in children from multisequence MRI using texture-based regression. AB - PURPOSE: This paper presents a statistical approach for the prediction of trabecular bone parameters from low-resolution multisequence magnetic resonance imaging (MRI) in children, thus addressing the limitations of high-resolution modalities such as HR-pQCT, including the significant exposure of young patients to radiation and the limited applicability of such modalities to peripheral bones in vivo. METHODS: A statistical predictive model is constructed from a database of MRI and HR-pQCT datasets, to relate the low-resolution MRI appearance in the cancellous bone to the trabecular parameters extracted from the high-resolution images. The description of the MRI appearance is achieved between subjects by using a collection of feature descriptors, which describe the texture properties inside the cancellous bone, and which are invariant to the geometry and size of the trabecular areas. The predictive model is built by fitting to the training data a nonlinear partial least square regression between the input MRI features and the output trabecular parameters. RESULTS: Detailed validation based on a sample of 96 datasets shows correlations >0.7 between the trabecular parameters predicted from low-resolution multisequence MRI based on the proposed statistical model and the values extracted from high-resolution HRp-QCT. CONCLUSIONS: The obtained results indicate the promise of the proposed predictive technique for the estimation of trabecular parameters in children from multisequence MRI, thus reducing the need for high-resolution radiation-based scans for a fragile population that is under development and growth. PMID- 27277055 TI - A novel approach to background subtraction in contrast-enhanced dual-energy digital mammography with commercially available mammography devices: Noise minimization. AB - PURPOSE: Dual-energy image subtraction represents a useful tool to improve the detectability of small lesions, especially in dense breasts. A feature it shares with all x-ray imaging techniques is the appearance of fluctuations in the texture of the background, which can obscure the visibility of interesting details. The aim of the work is to investigate the main noise sources, in order to create a better performing subtraction mechanism. In particular, the structural noise cancellation was achieved by means of a suitable extension of the dual-energy algorithm. METHODS: The effect of the cancellation procedure was tested on an analytical simulation of a target with varying structural composition. Subsequently, the subtraction algorithm was also applied to a set of actual radiographs of a breast phantom exhibiting a nonuniform background pattern. The background power spectra of the outcomes were computed and compared to the ones obtained from a standard subtraction algorithm. RESULTS: The comparison between the standard and the proposed cancellations showed an overall suppression of the magnitudes of the spectra, as well as a flattening of the frequency dependence of the structural component of the noise. CONCLUSIONS: The proposed subtraction procedure provides an effective cancellation of the residual background fluctuations. When combined with the polychromatic correction already described in a companion publication, it results in a high performing dual-energy subtraction scheme for commercial mammography units. PMID- 27277056 TI - Segmentation of prostate from ultrasound images using level sets on active band and intensity variation across edges. AB - PURPOSE: In this paper, the authors propose a novel efficient method to segment ultrasound images of the prostate with weak boundaries. Segmentation of the prostate from ultrasound images with weak boundaries widely exists in clinical applications. One of the most typical examples is the diagnosis and treatment of prostate cancer. Accurate segmentation of the prostate boundaries from ultrasound images plays an important role in many prostate-related applications such as the accurate placement of the biopsy needles, the assignment of the appropriate therapy in cancer treatment, and the measurement of the prostate volume. METHODS: Ultrasound images of the prostate are usually corrupted with intensity inhomogeneities, weak boundaries, and unwanted edges, which make the segmentation of the prostate an inherently difficult task. Regarding to these difficulties, the authors introduce an active band term and an edge descriptor term in the modified level set energy functional. The active band term is to deal with intensity inhomogeneities and the edge descriptor term is to capture the weak boundaries or to rule out unwanted boundaries. The level set function of the proposed model is updated in a band region around the zero level set which the authors call it an active band. The active band restricts the authors' method to utilize the local image information in a banded region around the prostate contour. Compared to traditional level set methods, the average intensities inside?outside the zero level set are only computed in this banded region. Thus, only pixels in the active band have influence on the evolution of the level set. For weak boundaries, they are hard to be distinguished by human eyes, but in local patches in the band region around prostate boundaries, they are easier to be detected. The authors incorporate an edge descriptor to calculate the total intensity variation in a local patch paralleled to the normal direction of the zero level set, which can detect weak boundaries and avoid unwanted edges in the ultrasound images. RESULTS: The efficiency of the proposed model is demonstrated by experiments on real 3D volume images and 2D ultrasound images and comparisons with other approaches. Validation results on real 3D TRUS prostate images show that the authors' model can obtain a Dice similarity coefficient (DSC) of 94.03% +/- 1.50% and a sensitivity of 93.16% +/- 2.30%. Experiments on 100 typical 2D ultrasound images show that the authors' method can obtain a sensitivity of 94.87% +/- 1.85% and a DSC of 95.82% +/- 2.23%. A reproducibility experiment is done to evaluate the robustness of the proposed model. CONCLUSIONS: As far as the authors know, prostate segmentation from ultrasound images with weak boundaries and unwanted edges is a difficult task. A novel method using level sets with active band and the intensity variation across edges is proposed in this paper. Extensive experimental results demonstrate that the proposed method is more efficient and accurate. PMID- 27277057 TI - Dynamic PET simulator via tomographic emission projection for kinetic modeling and parametric image studies. AB - PURPOSE: To develop and evaluate a fast and simple tool called dpetstep (Dynamic PET Simulator of Tracers via Emission Projection), for dynamic PET simulations as an alternative to Monte Carlo (MC), useful for educational purposes and evaluation of the effects of the clinical environment, postprocessing choices, etc., on dynamic and parametric images. METHODS: The tool was developed in matlab using both new and previously reported modules of petstep (PET Simulator of Tracers via Emission Projection). Time activity curves are generated for each voxel of the input parametric image, whereby effects of imaging system blurring, counting noise, scatters, randoms, and attenuation are simulated for each frame. Each frame is then reconstructed into images according to the user specified method, settings, and corrections. Reconstructed images were compared to MC data, and simple Gaussian noised time activity curves (GAUSS). RESULTS: dpetstep was 8000 times faster than MC. Dynamic images from dpetstep had a root mean square error that was within 4% on average of that of MC images, whereas the GAUSS images were within 11%. The average bias in dpetstep and MC images was the same, while GAUSS differed by 3% points. Noise profiles in dpetstep images conformed well to MC images, confirmed visually by scatter plot histograms, and statistically by tumor region of interest histogram comparisons that showed no significant differences (p < 0.01). Compared to GAUSS, dpetstep images and noise properties agreed better with MC. CONCLUSIONS: The authors have developed a fast and easy one-stop solution for simulations of dynamic PET and parametric images, and demonstrated that it generates both images and subsequent parametric images with very similar noise properties to those of MC images, in a fraction of the time. They believe dpetstep to be very useful for generating fast, simple, and realistic results, however since it uses simple scatter and random models it may not be suitable for studies investigating these phenomena. dpetstep can be downloaded free of cost from https://github.com/CRossSchmidtlein/dPETSTEP. PMID- 27277058 TI - Multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. AB - PURPOSE: This paper describes the design, fabrication, and characterization of multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. The phantoms comprise epidermis, dermis, and hypodermis skin layers, blood vessels, and blood mimicking fluid. Each tissue component may be individually tailored to a range of physiological and demographic conditions. METHODS: The skin layers were constructed from varying concentrations of gelatin and agar. Synthetic melanin, India ink, absorbing dyes, and Intralipid were added to provide optical absorption and scattering in the skin layers. Bovine serum albumin was used to increase acoustic attenuation, and 40 MUm diameter silica microspheres were used to induce acoustic backscatter. Phantom vessels consisting of thin-walled polydimethylsiloxane tubing were embedded at depths of 2-6 mm beneath the skin, and blood mimicking fluid was passed through the vessels. The phantoms were characterized through uniaxial compression and tension experiments, rheological frequency sweep studies, diffuse reflectance spectroscopy, and ultrasonic pulse-echo measurements. Results were then compared to in vivo and ex vivo literature data. RESULTS: The elastic and dynamic shear behavior of the phantom skin layers and vessel wall closely approximated the behavior of porcine skin tissues and human vessels. Similarly, the optical properties of the phantom tissue components in the wavelength range of 400-1100 nm, as well as the acoustic properties in the frequency range of 2-9 MHz, were comparable to human tissue data. Normalized root mean square percent errors between the phantom results and the literature reference values ranged from 1.06% to 9.82%, which for many measurements were less than the sample variability. Finally, the mechanical and imaging characteristics of the phantoms were found to remain stable after 30 days of storage at 21 degrees C. CONCLUSIONS: The phantoms described in this work simulate the mechanical, optical, and acoustic properties of human skin tissues, vessel tissue, and blood. In this way, the phantoms are uniquely suited to serve as test models for multimodal imaging techniques and image-guided interventions. PMID- 27277059 TI - Automated multistructure atlas-assisted detection of lymph nodes using pelvic MR lymphography in prostate cancer patients. AB - PURPOSE: To investigate whether atlas-based anatomical information can improve a fully automated lymph node detection system for pelvic MR lymphography (MRL) images of patients with prostate cancer. METHODS: Their data set contained MRL images of 240 prostate cancer patients who had an MRL as part of their clinical work-up between January 2008 and April 2010, with ferumoxtran-10 as contrast agent. Each MRL consisted of at least a 3D T1-weighted sequence, a 3D T2* weighted sequence, and a FLASH-3D sequence. The reference standard was created by two expert readers, reading in consensus, who annotated and interactively segmented the lymph nodes in all MRL studies. A total of 5089 lymph nodes were annotated. A fully automated computer-aided detection (CAD) system was developed to find lymph nodes in the MRL studies. The system incorporates voxel features based on image intensities, the Hessian matrix, and spatial position. After feature calculation, a GentleBoost-classifier in combination with local maxima detection was used to identify lymph node candidates. Multiatlas based anatomical information was added to the CAD system to assess whether this could improve performance. Using histogram analysis and free-receiver operating characteristic analysis, this was compared to a strategy where relative position features were used to encode anatomical information. RESULTS: Adding atlas-based anatomical information to the CAD system reduced false positive detections both visually and quantitatively. Median likelihood values of false positives decreased significantly in all annotated anatomical structures. The sensitivity increased from 53% to 70% at 10 false positives per lymph node. CONCLUSIONS: Adding anatomical information through atlas registration significantly improves an automated lymph node detection system for MRL images. PMID- 27277061 TI - Conformal image-guided microbeam radiation therapy at the ESRF biomedical beamline ID17. AB - PURPOSE: Upcoming veterinary trials in microbeam radiation therapy (MRT) demand for more advanced irradiation techniques than in preclinical research with small animals. The treatment of deep-seated tumors in cats and dogs with MRT requires sophisticated irradiation geometries from multiple ports, which impose further efforts to spare the normal tissue surrounding the target. METHODS: This work presents the development and benchmarking of a precise patient alignment protocol for MRT at the biomedical beamline ID17 of the European Synchrotron Radiation Facility (ESRF). The positioning of the patient prior to irradiation is verified by taking x-ray projection images from different angles. RESULTS: Using four external fiducial markers of 1.7 mm diameter and computed tomography-based treatment planning, a target alignment error of less than 2 mm can be achieved with an angular deviation of less than 2(?). Minor improvements on the protocol and the use of smaller markers indicate that even a precision better than 1 mm is technically feasible. Detailed investigations concerning the imaging dose lead to the conclusion that doses for skull radiographs lie in the same range as dose reference levels for human head radiographs. A currently used online dose monitor for MRT has been proven to give reliable results for the imaging beam. CONCLUSIONS: The ESRF biomedical beamline ID17 is technically ready to apply conformal image-guided MRT from multiple ports to large animals during future veterinary trials. PMID- 27277062 TI - A concept for classification of optimal breathing pattern for use in radiotherapy tracking, based on respiratory tumor kinematics and minimum jerk analysis. AB - PURPOSE: During radiotherapy, maintaining the patient in a relaxed and comfortable state helps ensure respiratory regularity and reproducibility, thereby supports accurate respiratory tracking/gating treatment. Criteria to evaluate respiratory naturalness, regularity, and phase robustness are therefore needed to aid for the treatment system numerically and medical observers visually. This study introduces a new concept of respiratory tumor kinematics that describes the trajectory of tumor motion with respiration, leading to the minimum jerk theory. Using this theory, this study proposes novel respiratory criteria for respiratory naturalness, regularity, and phase robustness. METHODS: According to respiratory tumor kinematics, tumor motion follows the minimum curvature/jerk trajectory in 4D spacetime. Using this theory, the following three respiratory criteria are proposed: (1) respiratory naturalness Us, the residual sum of the squared difference between the normalized average free respiratory wave (single inhalation/exhalation averaged over each 10 phases) and the normalized minimum jerk theoretical respiratory wave; (2) respiratory regularity Cj16, the cumulative jerk squared cost function sampling every 0.2 s with a peak adjustment coefficient, 16; and (3) respiratory phase robustness (LDelta), a second-order partial differential in the respiratory position for regarded Cj16 as the respiratory position function. To verify these respiratory criteria, values obtained from CyberKnife tracking marker log data for 15 patients were compared with regard to the correlation error between the correlation model and the imaged tumor position, as well as with the number of remodels. The Cj16 growth curve was also compared between 15 patients and 15 healthy volunteers. RESULTS: In the 15 patients, data with Us < 1 and Cj16(60 s) < 10 000 satisfied average/maximum correlation errors of less than 1/3 mm. Data with higher Us values (less respiratory naturalness) and higher Cj16(60 s) values (less respiratory regularity) demonstrated more than 3 mm average/5 mm maximum correlation errors and an increased number of remodels. The data for the 15 patients and 15 volunteers demonstrated that the Cj16 growth curve over 120 s from the start of sampling indicated patient-specific respiratory trends and that the distribution of LDelta clearly showed the respiratory phase shift. In 22 of 30 subjects, the degree of change in the Cj growth curve trends from 60 to 120 s was 22% +/- 13% (average +/- SD). In contrast, the residual data observed when Cj16 > 1000 showed minimum and mean changes of 91% and 180%, respectively. CONCLUSIONS: The authors developed and verified novel respiratory criteria for respiratory naturalness, regularity, and phase robustness obtained using respiratory tumor kinematics and minimum jerk analysis. These criteria should be useful in monitoring respiratory trends on a real-time basis during treatment, as well as in selecting optimal breathing for tracking/gating radiation treatment and defining numerical goals for respiratory training/gating. PMID- 27277063 TI - Guidelines by the AAPM and GEC-ESTRO on the use of innovative brachytherapy devices and applications: Report of Task Group 167. AB - Although a multicenter, Phase III, prospective, randomized trial is the gold standard for evidence-based medicine, it is rarely used in the evaluation of innovative devices because of many practical and ethical reasons. It is usually sufficient to compare the dose distributions and dose rates for determining the equivalence of the innovative treatment modality to an existing one. Thus, quantitative evaluation of the dosimetric characteristics of innovative radiotherapy devices or applications is a critical part in which physicists should be actively involved. The physicist's role, along with physician colleagues, in this process is highlighted for innovative brachytherapy devices and applications and includes evaluation of (1) dosimetric considerations for clinical implementation (including calibrations, dose calculations, and radiobiological aspects) to comply with existing societal dosimetric prerequisites for sources in routine clinical use, (2) risks and benefits from a regulatory and safety perspective, and (3) resource assessment and preparedness. Further, it is suggested that any developed calibration methods be traceable to a primary standards dosimetry laboratory (PSDL) such as the National Institute of Standards and Technology in the U.S. or to other PSDLs located elsewhere such as in Europe. Clinical users should follow standards as approved by their country's regulatory agencies that approved such a brachytherapy device. Integration of this system into the medical source calibration infrastructure of secondary standard dosimetry laboratories such as the Accredited Dosimetry Calibration Laboratories in the U.S. is encouraged before a source is introduced into widespread routine clinical use. The American Association of Physicists in Medicine and the Groupe Europeen de Curietherapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) have developed guidelines for the safe and consistent application of brachytherapy using innovative devices and applications. The current report covers regulatory approvals, calibration, dose calculations, radiobiological issues, and overall safety concerns that should be addressed during the commissioning stage preceding clinical use. These guidelines are based on review of requirements of the U.S. Nuclear Regulatory Commission, U.S. Department of Transportation, International Electrotechnical Commission Medical Electrical Equipment Standard 60601, U.S. Food and Drug Administration, European Commission for CE Marking (Conformite Europeenne), and institutional review boards and radiation safety committees. PMID- 27277060 TI - Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention. AB - Surgical guidance with fluorescence has been demonstrated in individual clinical trials for decades, but the scientific and commercial conditions exist today for a dramatic increase in clinical value. In the past decade, increased use of indocyanine green based visualization of vascular flow, biliary function, and tissue perfusion has spawned a robust growth in commercial systems that have near infrared emission imaging and video display capabilities. This recent history combined with major preclinical innovations in fluorescent-labeled molecular probes, has the potential for a shift in surgical practice toward resection guidance based upon molecular information in addition to conventional visual and palpable cues. Most surgical subspecialties already have treatment management decisions partially based upon the immunohistochemical phenotype of the cancer, as assessed from molecular pathology of the biopsy tissue. This phenotyping can inform the surgical resection process by spatial mapping of these features. Further integration of the diagnostic and therapeutic value of tumor metabolism sensing molecules or immune binding agents directly into the surgical process can help this field mature. Maximal value to the patient would come from identifying the spatial patterns of molecular expression in vivo that are well known to exist. However, as each molecular agent is advanced into trials, the performance of the imaging system can have a critical impact on the success. For example, use of pre-existing commercial imaging systems are not well suited to image receptor targeted fluorophores because of the lower concentrations expected, requiring orders of magnitude more sensitivity. Additionally the imaging system needs the appropriate dynamic range and image processing features to view molecular probes or therapeutics that may have nonspecific uptake or pharmacokinetic issues which lead to limitations in contrast. Imaging systems need to be chosen based upon objective performance criteria, and issues around calibration, validation, and interpretation need to be established before a clinical trial starts. Finally, as early phase trials become more established, the costs associated with failures can be crippling to the field, and so judicious use of phase 0 trials with microdose levels of agents is one viable paradigm to help the field advance, but this places high sensitivity requirements on the imaging systems used. Molecular guided surgery has truly transformative potential, and several key challenges are outlined here with the goal of seeing efficient advancement with ideal choices. The focus of this vision 20/20 paper is on the technological aspects that are needed to be paired with these agents. PMID- 27277064 TI - Erratum: "Coverage-based treatment planning to accommodate deformable organ variations in prostate cancer treatment" [Med. Phys. 41(10), 101705 (14pp.) (2014)]. PMID- 27277065 TI - Imaging in Nuclear Medicine. PMID- 27277066 TI - Molecular Imaging of Small Animals. PMID- 27277067 TI - Identification of a bipartite nuclear localization signal in the silkworm Masc protein. AB - The silkworm Masculinizer (Masc) gene encodes a CCCH-tandem zinc finger protein that controls both masculinization and dosage compensation. Masc protein is a nuclear protein, but the mechanism underlying the transport of this protein into the nucleus has not yet been elucidated. Here, we identified a functional bipartite nuclear localization signal (NLS) located between residues 274 and 290 of the Masc protein. Sequence comparison revealed that this bipartite NLS is evolutionarily conserved in Masc proteins from other lepidopteran insects. Furthermore, we showed that the degree of nuclear localization is not associated with the masculinizing activity of the Masc protein. PMID- 27277068 TI - Protection of densely populated excited triplet state ensembles against deactivation by molecular oxygen. AB - This critical review discusses different approaches towards protection of photoactive materials based on triplet excited state ensembles against deactivation by molecular oxygen though quenching and photooxidation mechanisms. Passive protection, based on the application of barrier materials for packaging, sealing, or encapsulation of the active substances, which prevent oxygen molecules from penetration and physical contact with excited states and active protection, based on the application of oxygen scavenging species are compared. Efficiencies of different approaches together with examples and prospects of their applications are outlined. PMID- 27277070 TI - Severity of nasal obstruction can predict the anxiety status of patients with allergic rhinitis but not patients with vasomotor rhinitis. AB - BACKGROUND: Allergic rhinitis (AR) is a chronic systemic allergic disease with an association reported between allergy and anxiety. The objective of the current study was therefore to investigate and retrospectively evaluate the factors that may possibly induce state and trait anxiety among patients with AR and vasomotor rhinitis (VMR). METHODS: A total of 253 outpatients suffering from AR and 108 suffering from VMR were assessed for nasal symptoms experienced during the 14 days prior to assessment. All patients scored the severity of their symptoms on a visual analogue scale (VAS) and answered the State-Trait Anxiety Inventory (STAI) questionnaire to evaluate their state (STAI-S) and trait (STAI-T) anxiety scores. Pearson's correlation and multiple regression tests were employed to assess correlations between symptom scores and anxiety status scores. RESULTS: The STAI S/T scores were not significantly different between AR and VMR patients; however, for AR patients, STAI-S and STAI-T were significantly associated with nasal obstruction and the total nasal symptom scores. Multiple regression analysis further demonstrated that only nasal obstruction significantly influenced both STAI-S and STAI-T scores. In contrast, nasal itching and total nasal symptom scores were significantly correlated with the STAI-S and STAI-T scores in VMR patients, whereas continuous sneezing VAS scores were significantly associated with only the STAI-S score. However, multiple regression analysis showed that the associations between any of the 4 nasal symptom scores and STAI-S and STAI-T scores were not significant. CONCLUSION: Nasal obstruction may play a prominent role in mediation of anxiety in patients suffering from AR, but not in patients suffering from VMR. PMID- 27277069 TI - Transcriptomic analysis of the ion channelome of human platelets and megakaryocytic cell lines. AB - Ion channels have crucial roles in all cell types and represent important therapeutic targets. Approximately 20 ion channels have been reported in human platelets; however, no systematic study has been undertaken to define the platelet channelome. These membrane proteins need only be expressed at low copy number to influence function and may not be detected using proteomic or transcriptomic microarray approaches. In our recent work, quantitative real-time PCR (qPCR) provided key evidence that Kv1.3 is responsible for the voltage dependent K+ conductance of platelets and megakaryocytes. The present study has expanded this approach to assess relative expression of 402 ion channels and channel regulatory genes in human platelets and three megakaryoblastic/erythroleukaemic cell lines. mRNA levels in platelets are low compared to other blood cells, therefore an improved method of isolating platelets was developed. This used a cocktail of inhibitors to prevent formation of leukocyte-platelet aggregates, and a combination of positive and negative immunomagnetic cell separation, followed by rapid extraction of mRNA. Expression of 34 channel-related transcripts was quantified in platelets, including 24 with unknown roles in platelet function, but that were detected at levels comparable to ion channels with established roles in haemostasis or thrombosis. Trace expression of a further 50 ion channel genes was also detected. More extensive channelomes were detected in MEG-01, CHRF-288-11 and HEL cells (195, 185 and 197 transcripts, respectively), but lacked several channels observed in the platelet. These "channelome" datasets provide an important resource for further studies of ion channel function in the platelet and megakaryocyte. PMID- 27277071 TI - The clinical results of a novel method for minimal invasive dynamic hip screw fixation of intertrochanteric fractures compared to the conventional one. AB - PURPOSE: Hip intertrochanteric fractures are very frequent. Early mobilization reduces the associated mortality and morbidity rate. DHS is still commonly used in many centers. We describe a new minimal invasive DHS technique (MIDHS) depending on radiological land marks, facilitating the application of DHS in a proper way without the use of an angle guide and we retrospectively compared the functional results of the new technique with that of the conventional DHS (CDHS) technique. METHODS: 116 patients (MIDHS n = 56; CDHS n = 60) with stable intertrochanteric fractures were followed up for at least 12 months. The motoric function using the Barthel index, the post-operative pain using the VAS, and the time of bone healing of the new MIDHS group were compared to that of the CDHS group. RESULTS: The 1st, 2nd, 3rd, 7th, 15th, and 45th days showed a higher motoric function of the MIDHS compared with the CDHS, P (0.001, 0.032, 0.012, 0.001, 0.028 and 0.041), respectively. VAS demonstrated less scores of the MIDHS group in the 1st, 2nd, 3rd, 7th, 15th, and 45th days when compared with that of the CDHS group, P (0.001, 0.032, 0.012, 0.001, 0.028, and 0.041), respectively. However, no statistical significance was detected in bone-healing time between the two groups. CONCLUSIONS: The new MIDHS technique is a trustable procedure that may help the surgeon to perform DHS fixation in a proper way. It offers a better motoric function, less pain. However, further studies should be conducted to evaluate the validity of such radiological land marks in proximal femoral surgery. PMID- 27277072 TI - The characteristics and pre-hospital management of blunt trauma patients with suspected spinal column injuries: a retrospective observational study. AB - BACKGROUND: Pre-hospital spinal immobilisation by emergency medical services (EMS) staff is currently the standard of care in cases of suspected spinal column injuries. There is, however, a lack of data on the characteristics of patients who received spinal immobilisation during the pre-hospital phase and on the adverse effects of immobilisation. The objectives of this study were threefold. First, we determined the pre-hospital characteristics of blunt trauma patients with suspected spinal column injuries who were immobilised by EMS staff. Second, we assessed the choices made by EMS staff regarding spinal immobilisation techniques and reasons for immobilisation. Third, we researched the possible adverse effects of immobilisation. DESIGN: A retrospective observational study in a cohort of blunt trauma patients. STUDY METHOD: Data of blunt trauma patients with suspected spinal column injuries were collected from one EMS organisation between January 2008 and January 2013. Coded data and free text notes were analysed. RESULTS: A total of 1082 patients were included in this study. Spinal immobilisation was applied in 96.3 % of the patients based on valid pre-hospital criteria. In 2.1 % of the patients immobilisation was not based on valid criteria. Data of 1.6 % patients were missing. Main reasons for spinal immobilisation were posterior midline spinal tenderness (37.2 % of patients) and painful distracting injuries (13.5 % of patients). Spinal cord injury (SCI) was suspected in 5.7 % of the patients with posterior midline spinal tenderness. A total of 15.8 % patients were immobilised using non-standard methods. The reason for departure from the standard method was explained for 3 % of these patients. Reported adverse effects included pain (n = 10, 0.9 %,); shortness of breath (n = 3, 0.3 %); combativeness or anxiety (n = 6, 0.6 %); and worsening of pain when supine (n = 1, 0.1 %). CONCLUSION/RECOMMENDATION: Spinal immobilisation was applied in 96.3 % of all included patients based on pre-hospital criteria. We found that consensus among EMS staff on how to interpret the criterion 'distracting injury' was lacking. Furthermore, the adverse effects of spinal immobilisation were incompletely documented in pre-hospital care reports. To provide validated information on potential symptoms of SCI, a uniform EMS scoring system for motoric assessment should be developed. PMID- 27277073 TI - A revised 3-column classification approach for the surgical planning of extended lateral tibial plateau fractures. AB - OBJECTIVES: Variable angle locking compression plates allow for lateral buttress and support of the posterolateral joint surface of tibial plateau fractures. This gives room for improvement of the surgical 3-column classification approach. Our aim was to revise and validate the 3-column classification approach to better guide the surgical planning of tibial plateau fractures extending into the posterolateral corner. METHODS: In contrast to the 3-column classification approach, in the revised approach the posterior border of the lateral column in the revised approach lies posterior instead of anterior of the fibula. According to the revised 3-column classification approach, extended lateral column fractures are defined as single lateral column fractures extending posteriorly into the posterolateral corner. CT-images of 36 patients were reviewed and classified twice online according to Schatzker and revised 3-column classification approach by five observers. The intraobserver reliability was calculated using the Cohen's kappa and the interobserver reliability was calculated using the Fleiss' kappa. RESULTS: The intraobserver reliability showed substantial agreement according to Landis and Koch for both Schatzker and the revised 3-column classification approach (0.746 vs. 0.782 p = 0.37, Schatzker vs. revised 3-column, respectively). However, the interobserver reliability of the revised 3-column classification approach was significantly higher as compared to the Schatzker classification (0.531 vs. 0.669 p < 0.01, moderate vs. substantial agreement, Schatzker vs. revised 3-column, respectively). CONCLUSIONS: With the introduction of variable angle locking compression plates, the revised 3-column classification approach is a very helpful tool in the preoperative surgical planning of tibial plateau fractures, in particular, lateral column fractures that extend into the posterolateral corner. The revised 3-column classification approach is rather a practical supplement to the Schatzker classification. It has a significantly higher interobserver reliability as compared to the Schatzker classification, most likely due to the more simple nature of the revised 3-column classification approach. PMID- 27277074 TI - Lipopolysaccharide Attenuates the Cytotoxicity of Resveratrol in Transformed Mouse Macrophages. AB - Resveratrol and pterostilbene are natural products that are present in plants and have been incorporated into various dietary supplements. Numerous beneficial pharmacologic effects have been reported for these stilbenes; however, the mechanism by which these compounds exert a cytotoxic effect in RAW 264.7 macrophages has not been well characterized. We have previously described that resveratrol is toxic to these tumor-derived macrophages and that stimulation with lipopolysaccharide (LPS) reduces resveratrol toxicity via a mechanism that involves activation of toll like receptor 4. In the present work, we examined the cellular and molecular effects of resveratrol and the related compound pterostilbene by determining cell viability and caspase 3 activity in control and LPS-stimulated RAW 264.7 macrophages incubated with these stilbenes for 24 h. We found that LPS stimulation reduced the cytotoxicity of resveratrol but not of pterostilbene in these cells. When examined for effects on caspase 3 activation after a 24 h incubation, resveratrol and pterostilbene were each found to separately and significantly increase caspase 3 activity in these cells. LPS stimulation prevented caspase 3 activation by pterostilbene and reduced caspase 3 activation by resveratrol in RAW 264.7 macrophages. The data presented here indicate that LPS induces a phenotype switch in tumor-derived RAW 264.7 macrophages in which cells experiencing LPS in the presence of resveratrol or pterostilbene become less likely to activate the pro-apoptotic factor caspase 3. PMID- 27277075 TI - Glycemic Response to Corn Starch Modified with Cyclodextrin Glycosyltransferase and its Relationship to Physical Properties. AB - Corn starch was modified with cyclodextrin glycosyltransferase (CGTase) below the gelatinization temperature. The porous granules with or without CGTase hydrolysis products may be used as an alternative to modified corn starches in foods applications. The amount and type of hydrolysis products were determined, containing mainly beta-cyclodextrin (CD), which will influence pasting behavior and glycemic response in mice. Irregular surface and small holes were observed by microscopic analysis and differences in pasting properties were observed in the presence of hydrolysis products. Postprandial blood glucose in mice fed gelatinized enzymatically modified starch peaked earlier than their ungelatinized counterparts. However, in ungelatinized enzymatically modified starches, the presence of beta- CD may inhibit the orientation of amylases slowing hydrolysis, which may help to maintain lower blood glucose levels. Significant correlations were found between glycemic curves and viscosity pattern of starches. PMID- 27277076 TI - Assessment of pathogenicity and tissue distribution of infectious bronchitis virus strains (Italy 02 genotype) isolated from moroccan broiler chickens. AB - BACKGROUND: Avian infectious bronchitis (IB) is one of the most important viral diseases of poultry, affecting chickens of all ages and causing major economic losses in poultry flocks. Mass vaccination is conducted in Morocco using a vaccine against Massachusetts, which is the most dominant serotype; however no information about the pathogenesis and tissue distribution of the Moroccan Italy 02 genotype was reported. 40 one-day-old specific pathogen free chickens were divided randomly into four groups. Group1, 2 and 3 were inoculated intra oculo nasally with 103.5 EID50 of Italy02 viruses, and group 4 was kept as control. Chickens in each group were monitored for 14 days post-infection (pi). RESULTS: Chickens in all infected groups showed severe respiratory signs, which most of them have been reproduced on 2dpi, with varying times of appearance and disappearance. The infected birds appeared lethargic, reluctant to move, with specific respiratory clinical signs and macroscopic lesions. However no nephritis lesions or mortality were recorded in all groups. The specific histological lesions finding in all infected birds, exhibited tracheal lesions with mucosal thickening, hyperplasia of the surface epithelium, mononuclear inflammatory cell infiltrate of lamina propria. Primary and secondary bronchi, epithelial hyperplasia and mononuclear inflammatory cell infiltrate of the lamina propria were also observed. Tracheal lesions developed in all infected birds, confirm the ability of the three tested strains to induce respiratory disease. The results at 14 dpi also revealed that all strains were able to induce serological response. Virus re-isolation from infected organs and amplification of the viral RNA by real-time PCR proved the presence of the virus in lung and trachea of infected chicks. Neither re-isolation nor significant viral RNA detection were detected in the kidney. CONCLUSION: The results demonstrated that the three strains Italy02 genotype emerging in Moroccan poultry farms have a wide distribution for respiratory system, without kidney damage and without causing mortality. PMID- 27277077 TI - Patients with hepatic breast cancer metastases demonstrate highly specific profiles of matrix metalloproteinases MMP-2 and MMP-9 after SIRT treatment as compared to other primary and secondary liver tumours. AB - BACKGROUND: Patients with primary and metastatic liver malignancies represent a highly heterogeneous patient pool characterised by some of the shortest life expectancies amongst oncology patients. Investigation and better understanding of liver malignancies is an emerging field which requires high-quality multidisciplinary research and collaboration. METHODS: A study of 158 patients with primary hepatic carcinomas and secondary liver metastases, altogether 15 cancer types of different origin, who underwent selective internal radiation therapy (SIRT) with Yttrium(90) or transarterial chemoembolisation, was undertaken in an effort to detect distinguishing features with respect to activity profiles of both blood matrix metalloproteinase (MMP-2 and MMP-9). RESULTS: Noteworthy, stratification of all hepatic cancer groups with respect to MMP-2 and MMP-9 activities revealed characteristic patterns specifically in patients with hepatic breast cancer metastases who had undergone SIRT. In contrast to all other groups, these patients demonstrated well-consolidated profiles of both MMPs, reflecting a common feature, namely an immediate and durable increase of their activity after the SIRT treatment. Although the total number of patients in the breast cancer group is relatively small (15 patients), since increased activities of MMP-2 and MMP-9 are well known prognostic factors for poor outcomes of oncologic patients, the significance and clear group specificity (from 15 ones investigated here) of this previously unanticipated finding requires particular attention and further investigations. Particularly important is to determine, whether this increase of the metalloproteinase activity was provoked by SIRT, as well as whether special selection criteria are required for patients with breast cancer metastases to the liver who are being considered for SIRT. CONCLUSIONS: It is recommended that a more focused, multidisciplinary and large-scaled investigations of the possible adverse effects of SIRT in patients with advanced metastatic disease of breast cancer be undertaken, with an appropriate patients' stratification, set-up of the relevant patient profiles and disease modelling. PMID- 27277078 TI - Can domestic helpers moderate distress of offspring caregivers of cognitively impaired older adults? AB - OBJECTIVE: This study examined the moderating effect of domestic helpers on distress of offspring caring for parents with cognitive impairments and with or without behavioural problems. METHOD: This secondary analysis of data involved 5086 Hong Kong Chinese adults aged 60 or older applying for public long-term care services from 2010 to 2012. All variables were measured using the mandatory Hong Kong version of the Minimum Data Set-Home Care 2.0. RESULTS: Regarding taking care of parents with cognitive impairments, 10.7% of offspring primary caregivers were aided by domestic helpers, 55.54% reported distress, and 75.70% lived with their parents. Assistance from domestic helpers reduced offspring caregiver distress if the offspring provided psychological support to parents (ratio of OR = 0.655, p < .05) and were not living with parents (ratio of OR = 1.183, p < .01). CONCLUSION: These findings might suggest: a) the positive effects of audience on psychological responses to stress; b) caregiving is usually less stressful for informal caregivers not residing with care recipients. Conversely, having a domestic helper could add to caregiving distress if offspring caregivers live with their parents, most likely because offspring may witness difficulties that domestic helpers face in providing dementia care. PMID- 27277080 TI - Chelatococcus thermostellatus sp. nov., a new thermophile for bioplastic synthesis: comparative phylogenetic and physiological study. AB - The poly(3-hydroxybutyrate), PHB, accumulating thermophilic strain MW9(T), isolated from an aerobic organic waste treatment plant, was characterized by detailed physiological and phylogenetic studies. The strain is a Gram-stain negative, rod shaped, non-spore forming member of Alphaproteobacteria. It shows optimum growth at 50 degrees C. Based on 16S rRNA gene sequence similarity, the strain together with five very similar isolates, was affiliated to the genus Chelatococcus (Ibrahim et al. in J Appl Microbiol 109:1579-1590, 2010). Rep-PCR genomic fingerprints and partial dnaK gene sequence also revealed that these isolates are very similar, but differ from other Chelatococcus type strains. The major fatty acids were similar to those of other strains of the genus Chelatococcus. DNA-DNA hybridization of strain MW9(T) with Chelatococcus species type strains revealed 11.0-47.7 % relatedness. G+C content of DNA was 67.1 mol%, which is comparable with the other strains of Chelatococcus species. The physiological and phenotypic characteristics of the new strain MW9(T) are sufficient to differentiate it from previously described species in the genus Chelatococcus. Strain MW9(T) is considered to represent a novel species of the genus Chelatococcus, for which the name Chelatococcus thermostellatus is proposed. The type strain is MW9(T) (=LMG 27009(T) = DSM 28244(T)). Compared to known Chelatococcus strains, strain MW9(T) could be a potent candidate for bioplastic production at elevated temperature. PMID- 27277079 TI - Metabolome analysis of Saccharomyces cerevisiae and optimization of culture medium for S-adenosyl-L-methionine production. AB - S-Adenosyl-L-methionine (SAM) is a fine chemical used as a nutritional supplement and a prescription drug. It is industrially produced using Saccharomyces cerevisiae owing to its high SAM content. To investigate the optimization of culture medium components for higher SAM production, metabolome analysis was conducted to compare the intracellular metabolite concentrations between Kyokai no. 6 (high SAM-producing) and laboratory yeast S288C (control) under different SAM production conditions. Metabolome analysis and the result of principal component analysis showed that the rate-limiting step for SAM production was ATP supply and the levels of degradation products of adenosine nucleotides were higher in Kyokai 6 strain than in the S288C strain under the L-methionine supplemented condition. Analysis of ATP accumulation showed that the levels of intracellular ATP in the Kyokai 6 strain were also higher compared to those in the S288C strain. Furthermore, as expected from metabolome analysis, the SAM content of Kyokai 6 strain cultivated in the medium without yeast extract increased by 2.5-fold compared to that in the additional condition, by increasing intracellular ATP level with inhibited cell growth. These results suggest that high SAM production is attributed to the enhanced ATP supply with L-methionine condition and high efficiency of intracellular ATP consumption. PMID- 27277081 TI - Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in Streptomyces sp. CK4412. AB - Tautomycetin (TMC) is a linear polyketide metabolite produced by Streptomyces sp. CK4412 that has been reported to possess multiple biological functions including T cell-specific immunosuppressive and anticancer activities that occur through a mechanism of differential inhibition of protein phosphatases such as PP1, PP2A, and SHP2. We previously reported the characterization of the entire TMC biosynthetic gene cluster constituted by multifunctional type I polyketide synthase (PKS) assembly and suggested that the linear form of TMC could be generated via free acid chain termination by a narrow TMC thioesterase (TE) pocket. The modular nature of the assembly presents a unique opportunity to alter or interchange the native biosynthetic domains to produce targeted variants of TMC. Herein, we report swapping of the TMC TE domain sequence with the exact counterpart of the macrocyclic polyketide pikromycin (PIK) TE. PIK TE-swapped Streptomyces sp. CK4412 mutant produced not only TMC, but also a cyclized form of TMC, implying that the bioengineering based in vivo custom construct can be exploited to produce engineered macrolactones with new structural functionality. PMID- 27277083 TI - Three-dimensional ultrasound is increasing our knowledge of the fetus little by little. PMID- 27277082 TI - Disorder-related risk factors for revision total hip arthroplasty after hip hemiarthroplasty in displaced femoral neck fracture patients: a nationwide population-based cohort study. AB - BACKGROUND: The choice of primary hip hemiarthroplasty or total hip arthroplasty for displaced femoral neck fracture is still controversial. Revision hip arthroplasty not only increases risk and cost but also could result in worse outcome. Determining the risk factors for revision can help inform medical decision-making and aid in risk stratification of publicly reported outcomes. Therefore, we conducted a nationwide population-based study to identify the disease-related risk factors and construct a risk score nomogram to predict revision surgery. METHODS: Records of all 68,030 femoral neck fracture patients receiving partial hemiarthroplasty (HA) in 2000-2010, with no total hip arthroplasty (THA) or revision HA history, were collected from the National Health Insurance Research Database. Cox proportional hazard regression was used to estimate the risk of revision hip replacement (RHA). The score of each risk factor was the quotient of the regression coefficient of the variable by the regression coefficient for a 10-year increase in age. The predictive accuracy was tested using the area under the receiver operating characteristic curve (AUROC). RESULTS: The revision risk for hemiarthroplasty increased in male, those with schizophrenia and end-stage renal disease patients had 1.58-, 1.88-, and 1.74 fold revision HA risk (95 % confidence interval (CI) = 1.40-1.78, 1.26-2.79, and 1.29-2.34, respectively). In a predictive model, the cumulative risk score ranged from 0 to 13 with a 5.08 to 91.82 % 10-year predicted RHA risk. The percentage of AUROC for 10-year RHA risk in nomogram was 61.9 (95 % CI = 60.0-63.4). CONCLUSIONS: Males, schizophrenia and end-stage renal disease patients have higher risk of revision surgery after hemiarthroplasty for femoral neck fracture. PMID- 27277084 TI - Multiple-frequency ultrasonic imaging by transmitting pulsed waves of two frequencies. AB - PURPOSE: The aim of this study was realization of a broadband measurement system that is capable of effectively carrying out a frequency compound method. In the present method, the secondary wave components of difference and sum frequencies are generated along with the higher harmonic components through the nonlinear interaction of two-frequency ultrasound. A multiple-frequency beam is generated together with the initially radiated frequency components. METHODS: For the structure of a transducer capable of simultaneously radiating two sound waves with different frequencies, a coaxial arrangement of a circular-disc piezoelectric transducer and a ring piezoelectric transducer was designed. The radiating frequencies chosen were 2 and 8 MHz. In addition to the 4-MHz second harmonic sound of the 2-MHz primary sound, sounds of the 6-MHz difference frequency and the 10-MHz sum frequency can be generated. RESULTS: By measuring the acoustic pressure distribution, the formation of a multiple-frequency beam was confirmed. The signal-to-noise ratio in an agar-gel phantom image was increased by 5-6 dB with application of the frequency compound method. The validity of the proposed method was demonstrated through the generation of a human finger image. Further, it was found that the influence of the Doppler effect was small enough that almost all the secondary waves were attributable to the nonlinear propagation of sounds. CONCLUSIONS: A multiple-frequency sound beam was realized by radiating a two-frequency sound. The effectiveness of the presented method was demonstrated through actual imaging. PMID- 27277085 TI - Low-intensity ultrasound adjuvant therapy: enhancement of doxorubicin-induced cytotoxicity and the acoustic mechanisms involved. AB - PURPOSE: In this study, the effects of low-intensity pulsed ultrasound (LIU) as an adjuvant to doxorubicin (DOX) treatment was further investigated in comparison to hyperthermia as another widely used adjuvant. The effects were compared with respect to cell killing and apoptosis induction in U937 cells. Human primary liver cancer (PLC) cells were also used to evaluate the effects of the combinations. The use of an echo contrast agent was investigated for further enhancement of cytotoxicity. Finally, the acoustic mechanisms involved were investigated. METHODS: The effects of different treatment regimens on cell viability were determined using the Trypan blue dye-exclusion test. Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effects. RESULTS: The combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used. The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant. Moreover, the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration. The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation. Non-cavitational forces were also shown to contribute to the effect. CONCLUSION: This study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions. PMID- 27277086 TI - Assessment of left ventricular diastolic function using color kinesis: differentiation between normal and pseudonormalized patterns. AB - PURPOSE: Doppler examination of transmitral flow has been widely used to noninvasively assess left ventricular (LV) diastolic function. However, it has been demonstrated that transmitral flow velocity is dependent on LV relaxation and left atrial pressure. Increases in left atrial pressure compensate for the effects of impaired LV relaxation, frequently resulting in a "pseudonormalization" of the transmitral flow pattern. The purpose of this study was to assess whether analysis of diastolic color kinesis (CK) can be applied to differentiation between normal and pseudonormalized (PN) patterns of LV inflow. METHODS: We studied 60 subjects with a ratio of early to late transmitral peak velocities (E/A) greater than 1.0 according to conventional Doppler echocardiography. All subjects simultaneously underwent measurement of the early diastolic mitral annular velocity (e'), which was measured by tissue Doppler imaging, and LV ejection fraction (EF), which was calculated by the modified Simpson method. Study subjects were classified into the following three groups according to the value of e' and EF: (1) the normal group (e' > 10 cm/s, EF > 60%), including 20 subjects (mean age 35 +/- 10 years); (2) the PN1 group (e' < 7 cm/s, EF > 50%), consisting of 20 patients [mean age 63 +/- 11 years, 15 patients with hypertensive heart disease (HHD), 5 patients with aortic valve stenosis]; and (3) the PN2 group (e' < 7 cm/s, EF < 50%), consisting of 20 patients (mean age 61 +/- 17 years, 18 patients with dilated cardiomyopathy, 2 patients with HHD). Diastolic CK images were obtained for each subject from the LV midpapillary short-axis view. Analysis of CK diastolic images was performed using ICK software. The CK-diastolic index (CK-DI) was defined as the calculated LV segmental filling fraction during the first 30% of diastole, expressed as a percentage. The mean CK-DI was determined from the average CK-DI of six LV segments. RESULTS: The mean CK-DI was 70.9% +/- 6.5% in the normal group, 46.3% +/- 10.4% in the PN1 group, and 36.3% +/- 5.1% in the PN2 group. The mean CK-DI was significantly reduced in the PN1 and PN2 groups compared with the normal group (P < 0.0001). Although there was no difference in e' (PN1 group: 4.6 +/- 1.8 cm/s, PN2 group: 4.4 +/- 1.7 cm/s) between the two pseudonormalized patient groups, the mean CK-DI was significantly reduced in the PN2 group compared with the PN1 group (P < 0.005). The reduction in mean CK-DI was seen not only in pseudonormalized patients with LV systolic dysfunction but also in those with preserved LV systolic function. CONCLUSION: The analysis of diastolic CK with ICK software is a useful method for detecting delayed early diastolic relaxation. We concluded that diastolic CK images may be applied to differentiating between normal and pseudonormalized patterns of LV inflow. PMID- 27277087 TI - Fetal preload index of the inferior vena cava and neonatal outcome of congenital diaphragmatic hernia. AB - PURPOSE: The purpose of this study was to assess prognostic factors in patients with congenital diaphragmatic hernia (CDH). METHODS: Thirteen patients with CDH diagnosed antenatally and delivered in our hospital between 1995 and 2006 were retrospectively studied. Assessments of sonographic examinations included gestational age at time of diagnosis; the ultrasonographic parameters [amniotic fluid index, cardiothoracic area ratio, and the lung-thoracic transverse area ratio (LTR)]; and the incidence of polyhydramnios, intrauterine growth retardation, and hydrops. Doppler velocimetry measurements comprised the resistance index of the umbilical artery, the resistance index of the midcerebral artery, the maximal velocity of the descending aorta, and the preload index of the inferior vena cava (IVCPLI). Results were expressed as the mean +/- standard deviation. The features of survivors and nonsurvivors were compared. RESULTS: Six fetuses were survivors and seven were nonsurvivors. The mean LTR value tended to be markedly low in both groups (23.8 +/- 16.4 vs 12.1 +/- 1.1). In Doppler analysis, the mean IVCPLI value in survivors was significantly lower than that in nonsurvivors (0.34 +/- 0.08 vs 0.52 +/- 0.14, P = 0.01). CONCLUSION: We concluded that fetal IVCPLI might be a good predictor of the outcome in patients with CDH. PMID- 27277088 TI - Feasibility of ultrasonography in determining the diagnosis and treatment of perforated duodenal ulcer. AB - PURPOSE: We diagnosed and treated perforated duodenal ulcers (PDUs) based on the results of ultrasonography (US). We obtained useful ultrasonographic findings regarding the diagnosis and treatment of PDU. METHODS: We experienced 24 PDU cases over 6 years and 4 months (March 2002 to June 2008), and evaluated five useful ultrasonographic findings regarding PDU: (1) Two-way transmigration of liquid and air bubbles through the perforated duodenal wall, (2) hyperechoic band penetration out through the duodenal wall, (3) free air exiting the PDU, (4) fluid exiting the PDU, and (5) liver covering the PDU. RESULTS: Of the 24 cases, two-way transmigration was observed in 4 cases, hyperechoic band penetration was observed in 18 cases, and exiting free air and fluid was observed in all cases. In all patients with two-way transmigration of liquid and air bubbles, we could immediately diagnose PDU. For the PDU cases falling under categories 2, 3, and 4 above, upon analysis, a large majority provided useful ultrasonographic findings for diagnosing PDU. Of the 5 cases in which the liver did not cover the PDU at all, two-way transmigration of liquid and air bubbles was observed in 4 cases, and surgery was performed in all 5 cases. Of the 19 cases where the PDU was completely covered by the surrounding organs (the liver in 16 cases and fatty organs such as the round ligament or the omentum in 3 cases), nonsurgical treatment was selected in 18 cases. As a result, patients with PDUs covered by surrounding organs, mainly by the liver, received nonsurgical treatment, whereas those with noncovered PDUs underwent surgery. CONCLUSION: The findings of ultrasonography are useful for diagnosing and determining the treatment of PDU. PMID- 27277089 TI - Epidermoid cyst appearing as a malignancy-mimicking subcutaneous lesion on ultrasonography. AB - PURPOSE: It is challenging to diagnose epidermoid cysts on ultrasonography; except in typical, benign-appearing cases. The purpose of this study was to include epidermoid cysts in the differential diagnosis of diverse subcutaneous lesions, especially malignancy-mimicking lesions, as seen on ultrasonography. METHODS: We reviewed 19 cases of pathologically confirmed epidermoid cysts in 19 patients (male, 8; female, 11). Three radiologists, who were blinded to the pathology data, classified (by consensus) these epidermoid cysts as benign or malignancy-mimicking lesions, according to generally accepted ultrasonographic criteria, including the margin, shape, echotexture, and transitional zone with surrounding tissue, and also including the growth pattern and adjacent tissue change. The ultrasonographic data were then correlated with the pathology results regarding the ruptured or unruptured status of the cysts. RESULTS: Epidermoid cysts have been noted as showing a wide-spectrum of findings on ultrasonography. Twelve of our cases showed benign ultrasonographic features: six cases had typical, benign ultrasonographic features with unruptured status; two cases with ruptured status did not have clear ultrasonographic features, although we decided by consensus that there were benign ultrasonographic features; and four cases with unruptured status had peculiar internal echogenicities, described as "internal rod-like contents", that could be considered to be a variation of the typical ultrasonographic finding of epidermoid cysts. Seven cases showed malignancy-mimicking ultrasonographic features; all seven of these had ruptured status. CONCLUSION: The diagnosis of ruptured epidermoid cysts should be included in the differential diagnosis of malignancy-mimicking subcutaneous lesions. The internal rod-like contents can be regarded as another typical ultrasonographic finding of epidermoid cysts. PMID- 27277090 TI - The thread and streaks sign. PMID- 27277091 TI - Mucin carriers of TF in ovarian cancer. PMID- 27277092 TI - Postoperative Bleeding and Leakage After Sleeve Gastrectomy: a Single-Center Experience. AB - BACKGROUND: Sleeve gastrectomy is being performed increasingly, mainly due to its low morbidity and mortality, but complications do occur. The aim of this study was to evaluate bleeding and leakage rates of primary and revisional sleeve gastrectomy in a personal series of 664 consecutive patients. METHODS: Medical charts of all patients undergoing a primary or revisional sleeve gastrectomy between August 2008 and December 2014 were reviewed retrospectively. Subgroup analysis compared bleeding in patients after reduced port versus multiport technique and primary versus revisional sleeve gastrectomy. RESULTS: A total of 664 sleeve gastrectomies (489 women and 175 men) were performed. Mean age and body mass index were 36.03 +/- 11.4 years and 42.9 +/- 8.3 kg/m2, respectively. Mean operative time was 58.5 +/- 20.0 min, with a 0.15 % conversion rate. Mean hospital stay was 2.1 +/- 0.3 days. The overall 30-day complication rate was 7.5 %. Thirteen patients sustained postoperative bleeding (2 %), three of whom required reoperation (0.5 %). Staple line leakage and mortality were both nil in this series. No difference in postoperative complications was found between the subgroups. CONCLUSIONS: In this single-surgeon, single-center experience, sleeve gastrectomy was a safe and effective bariatric procedure with a low complication rate. Staple line reinforcement by oversewing was associated with low bleeding complications and no leakage. The majority of patients with postoperative bleeding could be managed conservatively. In our experience, reduced port technique and revisional sleeve gastrectomy had similar complication rates compared to multiport and primary sleeve gastrectomy. PMID- 27277093 TI - Biological activity of soil contaminated with cobalt, tin, and molybdenum. AB - In this age of intensive industrialization and urbanization, mankind's highest concern should be to analyze the effect of all metals accumulating in the environment, both those considered toxic and trace elements. With this aim in mind, a unique study was conducted to determine the potentially negative impact of Sn(2+), Co(2+), and Mo(5+) in optimal and increased doses on soil biological properties. These metals were applied in the form of aqueous solutions of Sn(2+) (SnCl2 (.)2H2O), Co(2+) (CoCl2 . 6H2O), and Mo(5+) (MoCl5), each in the doses of 0, 25, 50, 100, 200, 400, and 800 mg kg(-1) soil DM. The activity of dehydrogenases, urease, acid phosphatase, alkaline phosphatase, arylsulfatase, and catalase and the counts of twelve microorganism groups were determined on the 25th and 50th day of experiment duration. Moreover, to present the studied problem comprehensively, changes in the biochemical activity and yield of spring barley were shown using soil and plant resistance indices-RS. The study shows that Sn(2+), Co(2+), and Mo(5+) disturb the state of soil homeostasis. Co(2+) and Mo(5+) proved the greatest soil biological activity inhibitors. The residence of these metals in soil, particularly Co(2+), also generated a drastic decrease in the value of spring barley resistance. Only Sn(2+) did not disrupt its yielding. The studied enzymes can be arranged as follows for their sensitivity to Sn(2+), Co(2+), Mo(5+): Deh > Ure > Aryl > Pal > Pac > Cat. Dehydrogenases and urease may be reliable soil health indicators. PMID- 27277094 TI - A road map for designing and implementing a biological monitoring program. AB - Designing and implementing natural resource monitoring is a challenging endeavor undertaken by many agencies, NGOs, and citizen groups worldwide. Yet many monitoring programs fail to deliver useful information for a variety of administrative (staffing, documentation, and funding) or technical (sampling design and data analysis) reasons. Programs risk failure if they lack a clear motivating problem or question, explicit objectives linked to this problem or question, and a comprehensive conceptual model of the system under study. Designers must consider what "success" looks like from a resource management perspective, how desired outcomes translate to appropriate attributes to monitor, and how they will be measured. All such efforts should be filtered through the question "Why is this important?" Failing to address these considerations will produce a program that fails to deliver the desired information. We addressed these issues through creation of a "road map" for designing and implementing a monitoring program, synthesizing multiple aspects of a monitoring program into a single, overarching framework. The road map emphasizes linkages among core decisions to ensure alignment of all components, from problem framing through technical details of data collection and analysis, to program administration. Following this framework will help avoid common pitfalls, keep projects on track and budgets realistic, and aid in program evaluations. The road map has proved useful for monitoring by individuals and teams, those planning new monitoring, and those reviewing existing monitoring and for staff with a wide range of technical and scientific skills. PMID- 27277095 TI - Rapid change in environment for research on diagnostic ultrasound. PMID- 27277096 TI - Measurement of regional pulse wave velocity using very high frame rate ultrasound. AB - PURPOSE: Pulse wave velocity (PWV) is the propagation velocity of the pressure wave along the artery due to the heartbeat. The PWV becomes faster with progression of arteriosclerosis and, thus, can be used as a diagnostic index of arteriosclerosis. Measurement of PWV is known as a noninvasive approach for diagnosis of arteriosclerosis and is widely used in clinical situations. In the traditional PWV method, the average PWV is calculated between two points, the carotid and femoral arteries, at an interval of several tens of centimeters. However, PWV depends on part of the arterial tree, i.e., PWVs in the distal arteries are faster than those in the proximal arteries. Therefore, measurement of regional PWV is preferable. METHODS: To evaluate regional PWV in the present study, the minute vibration velocity of the human carotid arterial wall was measured at intervals of 0.2 mm at 72 points in the arterial longitudinal direction by the phased-tracking method at a high temporal resolution of 3472 Hz, and PWV was estimated by applying the Hilbert transform to those waveforms. RESULTS: In the present study, carotid arteries of three healthy subjects were measured in vivo. The PWVs in short segments of 14.4 mm in the arterial longitudinal direction were estimated to be 5.6, 6.4, and 6.7 m/s, which were in good agreement with those reported in the literature. Furthermore, for one of the subjects, a component was clearly found propagating from the periphery to the direction of the heart, i.e., a well known component reflected by the peripheral arteries. By using the proposed method, the propagation speed of the reflection component was also separately estimated to be -8.4 m/s. The higher magnitude of PWV for the reflection component was considered to be the difference in blood pressure at the arrivals of the forward and reflection components. CONCLUSION: Such a method would be useful for more sensitive evaluation of the change in elasticity due to progression of arteriosclerosis by measuring the regional PWV in a specific artery of interest (not the average PWV including other arteries). PMID- 27277097 TI - A single-ensemble-based hybrid approach to clutter rejection combining bilinear Hankel with regression. AB - PURPOSE: Clutter regarded as ultrasound Doppler echoes of soft tissue interferes with the primary objective of color flow imaging (CFI): measurement and display of blood flow. Multi-ensemble samples based clutter filters degrade resolution or frame rate of CFI. The prevalent single-ensemble clutter rejection filter is based on a single rejection criterion and fails to achieve a high accuracy for estimating both the low- and high-velocity blood flow components. METHODS: The Bilinear Hankel-SVD achieved more exact signal decomposition than the conventional Hankel-SVD. Furthermore, the correlation between two arbitrary eigen components obtained by the B-Hankel-SVD was demonstrated. In the hybrid approach, the input ultrasound Doppler signal first passes through a low-order regression filter, and then the output is properly decomposed into a collection of eigen components under the framework of B-Hankel-SVD. The blood flow components are finally extracted based on a frequency threshold. RESULTS: In a series of simulations, the proposed B-Hankel-SVD filter reduced the estimation bias of the blood flow over the conventional Hankel-SVD filter. The hybrid algorithm was shown to be more effective than regression or Hankel-SVD filters alone in rejecting the undesirable clutter components with single-ensemble (S-E) samples. It achieved a significant improvement in blood flow frequency estimation and estimation variance over the other competing filters. PMID- 27277098 TI - Application of high-intensity focused ultrasound for fetal therapy: experimental study using an animal model of lower urinary tract obstruction. AB - OBJECTIVE: The purpose of this study is to investigate whether high-intensity focused ultrasound (HIFU) exposure is able to produce a fistula between the bladder and abdominal wall of a fetus with lower urinary tract obstruction (LUTO). MATERIALS AND METHODS: We constructed a prototype HIFU transducer in combination with an imaging probe. HIFU was applied to the lower abdomen of a rabbit neonate that was complicated by LUTO as an experimental model to produce a fistula; HIFU was applied in a tank filled with degassed water. Exposed lesions were assessed by histological analysis at necropsy. RESULTS: When HIFU was applied at 5.5 kW/cm(2) of spatial-peak temporal average intensity (SPTA), a fistula was created between the lower abdominal wall and the urinary bladder; urine gushed out from the bladder through the fistula within 60 s after HIFU exposure. CONCLUSION: The findings suggest that fetal diseases such as LUTO can be non-invasively treated using HIFU exposure from even outside the maternal body, though this study was performed in a water tank. PMID- 27277099 TI - Impact of milrinone on mitral annular velocity in patients with congestive heart failure. AB - PURPOSE: The purpose of this study is to assess the impact of milrinone on mitral annular velocity in patients with congestive heart failure. METHOD: We studied 27 patients with congestive heart failure. All patients underwent transthoracic echocardiography both before and after administration of milrinone. We measured the early transmitral velocity (E) and the mitral annular early diastolic velocity (Ea). The ratio of E to Ea (E/Ea) was calculated. After the baseline echocardiography, milrinone was administered as a continuous infusion at a rate of 0.25 MUg/kg/min. Echocardiographic measurements were repeated 4 h after milrinone was begun. RESULTS: After administration of milrinone, Ea was significantly increased, while E/Ea was significantly decreased. The population of 27 patients was divided into 20 (74 %) with left ventricular ejection fraction (LVEF) <50 % and seven (26 %) with LVEF >=50 %. Ea was significantly increased in both groups, while E/Ea was significantly decreased. CONCLUSION: Even low-dose milrinone produced an improvement in left ventricular (LV) diastolic function, as evidenced by an increase in Ea, and falls in LV filling pressures, as determined by a decrease in E/Ea, in patients with congestive heart failure throughout a wide range of LV systolic function. PMID- 27277101 TI - Transcranial contrast-enhanced ultrasonography with Sonazoid in semiquantitative evaluation of brain perfusion. AB - PURPOSE: To semiquantitatively evaluate brain perfusion by transcranial contrast enhanced ultrasonography (TCEUS) using Sonazoid. METHODS: We performed TCEUS in 11 healthy volunteers and seven patients with occlusive cerebrovascular disease involving the anterior circulation. After recording first-pass perfusion images on one side of the head and flush-replenishment (FR) images on both sides, we measured the time from arrival to peak (TAP) and peak intensity (PI) at first pass. Using the FR method, plateau value (A) and rise rate (beta) of intensity (I) were obtained from the curve I(t) = A(1 - e (-beta*t) ). RESULTS: In the patients, TAP was longer and PI was smaller in middle cerebral artery (MCA) areas than in posterior cerebral artery (PCA) areas on the ipsilesional side of the head (p < 0.05). A and beta were smaller in MCA areas than in PCA areas on the ipsilesional side of the head (p < 0.05), while these parameters showed no apparent differences between MCA and PCA areas in the volunteers. CONCLUSION: TCEUS with Sonazoid allows effective semiquantitative evaluation of brain perfusion. PMID- 27277100 TI - Longitudinal comparison study of pelvic floor function between women with and without stress urinary incontinence after vaginal delivery. AB - PURPOSE: To compare the pelvic floor function between women with and without stress urinary incontinence after vaginal delivery. METHODS: Seventeen women (age 35.5 +/- 3.5) were prospectively studied at about 6 weeks, 3 months, and 6 months after vaginal delivery. Urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire - Short Form. Pelvic floor function was assessed by antero-posterior diameter of the levator hiatus using transperineal ultrasound. RESULTS: Five of 17 women experienced postpartum stress urinary incontinence. The antero-posterior diameter of the levator hiatus at rest was significantly longer in stress urinary incontinent women than in continent women until 3 months after delivery (p < 0.01), though shortening of the antero posterior diameter of the levator hiatus was not significantly different between continent women and stress urinary incontinent women. Regardless of urinary incontinence, the antero-posterior diameter of the levator hiatus at rest shortened at 6 months postpartum, compared to 6 weeks postpartum (p < 0.001). The antero-posterior diameter of the levator hiatus during contraction had shortened only in continent women by 6 months postpartum (p = 0.02). CONCLUSION: The extended pelvic floor may be a cause of stress urinary incontinence in the postpartum period. Therefore, treatment to improve the extended pelvic floor should be developed for the prevention of stress urinary incontinence. PMID- 27277102 TI - Subvalvular aortic stenosis diagnosed by 3D transesophageal echocardiography. AB - The patient was a 13-year-old male with chief complaints of exertional chest pain and dyspnea. Cardiac murmur was suspected in a medical checkup at 1 month old, at which time he was diagnosed with subvalvular aortic stenosis. He had subsequently been under follow-up observation at a nearby hospital for subvalvular aortic stenosis. He was admitted to our department for surgery due to aggravation of symptoms that had occurred over the previous year. Transthoracic echocardiography after admission showed an abnormal structure in the subvalvular aortic area, and the maximum pressure gradient between the left ventricle and aortic valve was 84 mmHg. The preoperative valve area was 0.71 cm(2), as measured by the Doppler method. Measurement of valve area by the trace method was difficult. Transesophageal echocardiography (TEE) showed a septum-like structure extending from the ventricular septum in the subvalvular area. On 3D TEE, the valve areas in the systolic and diastolic phases were 0.86 and 0.49 cm(2), respectively. Postoperative echocardiography showed resection of the structure in the subvalvular area, and the postoperative course was favorable. PMID- 27277103 TI - A case of giant left main coronary artery aneurysm in an elderly man. AB - Aneurysms of the left main coronary artery are rare and their optimal treatments remain unknown. A 64-year-old man without any symptoms was referred to our department for suspected coronary aneurysm. Transthoracic echocardiography demonstrated an aneurysm of the left main coronary artery. On transesophageal echocardiography, the thrombus was suspected inside and severe ostial stenosis of the left coronary artery was highly suspected due to the accelerated flow velocity. Multidetector computed tomography demonstrated the aneurysm as being 37 mm in diameter with significant stenosis at both left coronary arteries, more clearly than coronary angiography. Because of its size and coexisting coronary artery disease, surgical closure of the aneurysm and coronary artery bypasses were performed. Echocardiography and coronary computed tomography could help in the diagnosis and the therapeutic decision in the case of left main coronary artery aneurysm before coronary angiography. PMID- 27277104 TI - Pilomatricoma of the breast in an adolescent girl: sonographic findings. AB - I report a case of pilomatricoma of the breast in an adolescent girl. Sonograms showed a solitary circumscribed, oval, heterogeneously hyperechoic mass in the skin. This is the first description of sonographic findings for this rare tumor in an adolescent breast. PMID- 27277105 TI - Congenital aortico-left ventricular tunnel in fetuses and infants. AB - Congenital aortico-left ventricular tunnel (ALVT) is a rare congenital heart disease. A 27-year-old woman was referred to us at 37 weeks gestation with fetal cardiac enlargement. The left ventricle (LV) of the fetus was enlarged. Fetal aortic valve (AoV) ring diameter spread was observed. Back flow from the AoV margins to the LV was observed. The prenatal diagnosis of the fetus was aortic regurgitation (AR). A male neonate was delivered by cesarean section at 40 weeks gestation. We made the diagnosis of ALVT because the aorta and the LV of the neonate showed a tunnel with blood flow on echocardiography. We took another look at the fetal echocardiography. The neonate underwent surgery for exacerbation of heart failure on the 7th day after birth. Trivial flow from the tunnel and mild AR were observed after surgery. PMID- 27277106 TI - Usefulness of ultrasonography and MRI for diagnosis of fetal pulmonary agenesis: case report and review of the literature. AB - A pregnant Japanese female was referred to our hospital due to intrauterine fetal growth restriction. A prenatal diagnosis of right pulmonary agenesis could be made using ultrasonography and fetal magnetic resonance imaging, and a Caesarian section was performed at 34 weeks of gestation. The infant developed a respiratory disorder immediately, received systemic management in the neonatal intensive care unit (NICU), and was discharged at age of 103 days without any severe sequelae. PMID- 27277107 TI - An accessory thyroid gland that presented tumor-like images. AB - A 26-year-old woman presented with right breast pain and itching. Incidentally, a firm, non-tender, movable mass (3 cm in diameter) located in the lower right part of the neck was identified by palpation. Ultrasonography revealed a clearly demarcated dumbbell-shaped mass with homogenous hypo- (cranial side) and hyper echogenicity (caudal side) compared with the thyroid gland. Computed tomography scan and magnetic resonance imaging presented images that were different from thyroid gland substance. The right thyroid lobe was strongly compressed by the mass. Hyperparathyroidism was ruled out by laboratory testing. The patient solicited resection of the mass despite recommendations for core needle biopsy, and it was removed surgically. The mass was surrounded by a thin capsule and was not connected with the thyroid gland. Pathological examinations revealed normal thyroid gland tissue. The final diagnosis was an accessory thyroid gland. Accessory thyroid glands should be considered as a possible diagnosis when nodules around the main thyroid gland are encountered. PMID- 27277109 TI - The effectiveness of "Protex" for disinfection of the ultrasound probe. AB - The aim of this study was to evaluate the effectiveness of "Protex" (Parker; Fairfield, NJ, USA) for disinfection of ultrasound probes. We examined bacterial contamination on ultrasound probes that were wiped with a plain paper towel, with a plain and an ethanol-soaked paper towel, or with a plain and Protex-soaked paper towel. The plain paper towel was used to remove the gel, and was contaminated by large numbers of bacteria, but the use of ethanol-soaked paper towels and that of paper towels soaked in ProtexTM broad-spectrum disinfectant (Parker: Fairfield, NJ, USA) reduced those numbers markedly. PMID- 27277110 TI - Ultrasonographic appearance of intestinal Ascaris. PMID- 27277108 TI - The value of ultrasound elastography-guided fine-needle aspiration biopsy of thyroid nodules in reducing nondiagnostic results. AB - Fine-needle aspiration biopsy (FNAB) is an important tool for diagnosing thyroid nodules; however, nondiagnostic results are a problem with FNAB. We evaluated the optimal targeting area of thyroid nodules for FNAB by using ultrasound elastography (USE) to reduce nondiagnostic results. Between December 2008 and November 2010, 96 consecutive prospective subjects scheduled to undergo FNAB were included in the study. Initially, the dominant nodule was evaluated with ultrasound, after which USE was performed. FNABs were performed from both the red (hard foci) and the green (soft foci) color-coded areas using the same technique according to the USE maps. The cellularity of all the specimens was evaluated cytopathologically. Nondiagnostic results from the red and green color-coded areas were compared by Chi-square test. In the red color-coded regions on USE images, the diagnostic rate was 76.0 % and the nondiagnostic rate was 24.0 %. In the green color-coded regions on USE images, the diagnostic rate was 53.1 % and the nondiagnostic rate was 46.9 %. Seven nodules were malignant and 89 were benign. Nondiagnostic results were significantly fewer in red color-coded regions (P = 0.0001). USE can help to enhance the cellularity of biopsy of thyroid nodules to reduce the nondiagnostic results if the red color-coded (less elastic or hard) areas are preferred. PMID- 27277111 TI - Three-dimensional HDlive-rendered images of intrauterine abnormalities during pregnancy. PMID- 27277112 TI - Antenatal three-dimensional sonographic features of multicystic dysplastic kidney. PMID- 27277113 TI - Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype. AB - BACKGROUND: The aim of this study was to investigate the expression and clinical implications of proteins related to serine/glycine metabolism in different subtypes of thyroid cancer. METHODS: Tissue microarray (TMA) was constructed with tissues from 557 thyroid cancers, consisting of 244 papillary thyroid carcinomas (PTC), 112 follicular carcinomas (FC), 70 medullary carcinomas (MC), 23 poorly differentiated carcinomas (PDC), and 8 anaplastic carcinomas (AC). Immunohistochemical staining of the serine/glycine metabolism-related molecules phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase, (PSAT), phosphoserine phosphatase (PSPH), serine hydromethyl transferase (SHMT), and glycine decarboxylase (GLDC) was performed with the TMA blocks and the results were analyzed together with clinicopathologic parameters. RESULTS: The expression of serine/glycine metabolism-related proteins differed among thyroid cancer subtypes. The expression rate of PHGDH (p < 0.001), PSAT1 (p = 0.001), PSPH (p = 0.008), and tumoral SHMT1 (p < 0.001) was higher in PDC and PTC (78.3, 21.7, 21.7, 30.4 and 63.4, 18.6, 12.8, 31.4 %, respectively), and lowest in MC (15.7, 1.4, 0.0, 10.0 %). Stromal SHMT1 expression was highest in AC (62.5 %) and absent in all FC (p < 0.001). In PTC, positivity for PSPH (p = 0.041), tumoral SHMT1 (p = 0.018), and stromal SHMT1 (p < 0.001) expression was higher in the conventional type compared to follicular type (14.1 versus 2.5 %, 33.6 versus 15.0 %, 42.1 versus 10.0 %, respectively). BRAF V600E mutation was associated with a higher rate of PHGDH (p < 0.001), PSAT1 (p = 0.001), PSPH (p < 0.001), tumoral SHMT1 (p = 0.001), stromal SHMT1 (p < 0.001), and GLDC (p < 0.001) expression compared to non-mutant cases (73.5 versus 40.6 %, 23.1 versus 8.5 %, 17.6 versus 1.9 %, 37.0 versus 18.9 %, 45.8 versus 21.7 %, 21.8 versus 6.6 %, respectively). In univariate analysis, stromal SHMT1 expression was associated with shorter disease free survival (p = 0.015) in follicular variant PTC, and GLDC positivity was associated with shorter overall survival (OS) in sclerotic stromal type (p = 0.002). In FC, minimally invasive type, PSPH positivity correlated with shorter OS (p = 0.045) and in MC, PHGDH positivity correlated with shorter OS (p = 0.034). CONCLUSION: The expression of serine/glycine metabolism-related proteins differs among different thyroid cancer types, with a higher rate of expression in PDC and PTC, and lower rate of expression in MC. In PTC, the rate of expression is lower in the follicular variant and higher in cases with BRAF V600E mutation. PMID- 27277114 TI - The association between built environment features and physical activity in the Australian context: a synthesis of the literature. AB - BACKGROUND: There is growing evidence indicating that the built environment is a determinant of physical activity. However, despite the well-established health benefits of physical activity this is rarely considered in urban planning. We summarised recent Australian evidence for the association built environment physical activity among adults. This summary aims to inform policy makers who advocate for the consideration of health in urban planning. METHODS: A combination of built environment and physical activity terms were used to systematically identify relevant peer reviewed and grey literature. RESULTS: A total of 23 studies were included, providing 139 tests of associations between specific built environment features and physical activity. Of the total, 84 relationships using objective measures of built environment attributes were evaluated, whereas 55 relationships using self-reported measures were evaluated. Our results indicate that walkable neighbourhoods with a wide range of local destinations to go to, as well as a diverse use of land, encourage physical activity among their residents. CONCLUSIONS: This research provides a summary of recent Australian evidence on built environments that are most favourable for physical activity. Features of walkability and availability of destinations within walking distance should be accounted for in the development or redevelopment of urban areas. Our findings emphasise the importance of urban planning for health via its impact on population levels of physical activity. PMID- 27277115 TI - Efficacy of chlorophyll c2 for seasonal allergic rhinitis: single-center double blind randomized control trial. AB - Chlorophyll c2 extracted from Sargassum horneri improved allergic symptoms in an animal model of allergic rhinitis. In the present study, we explored the efficacy of chlorophyll c2 in patients with seasonal allergic rhinitis. This was a single center, randomized, double-blind placebo-controlled trial. Sixty-six patients aged 20-43 years, each with a 2-year history of seasonal allergic rhinitis, were randomly assigned to receive either a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. The use of medications including H1-antihistamines and topical nasal steroids was recorded by rescue medication scores (RMSs) noted after 4, 8, and 12 weeks of treatment. Disease-specific quality of life was measured using the Japan Rhinitis Quality of Life Questionnaire (JRQLQ) both before and after 4, 8, and 12 weeks of treatment. The RMS at 8 weeks was significantly better in the chlorophyll c2 than the placebo group (mean RMS difference = -3.09; 95 % confidence interval = -5.96 to -0.22); the mean RMS at 4 weeks was only slightly better in the chlorophyll c2 group. The JRQLQ scores did not differ significantly between the two groups. Chlorophyll c2 would have a potential to be an alternative treatment for allergic rhinitis. PMID- 27277116 TI - Is Thyroglobulin Level by Liquid Chromatography Tandem-Mass Spectrometry Always Reliable for Follow-Up of DTC After Thyroidectomy: A Report on Two Patients. PMID- 27277117 TI - More Time for Science and Less Time for Administration? PMID- 27277120 TI - Progress in science and technology. PMID- 27277118 TI - Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma. AB - Adverse experiences in early life are risk factors for the development of behavioral and physiological symptoms that can lead to psychiatric and cognitive disorders later in life. Some of these symptoms can be transmitted to the offspring, in some cases by non-genomic mechanisms involving germ cells. Using a mouse model of unpredictable maternal separation and maternal stress, we show that postnatal trauma alters coping behaviors in adverse conditions in exposed males when adult and in their adult male progeny. The behavioral changes are accompanied by increased glucocorticoid receptor (GR) expression and decreased DNA methylation of the GR promoter in the hippocampus. DNA methylation is also decreased in sperm cells of exposed males when adult. Transgenerational transmission of behavioral symptoms is prevented by paternal environmental enrichment, an effect associated with the reversal of alterations in GR gene expression and DNA methylation in the hippocampus of the male offspring. These findings highlight the influence of both negative and positive environmental factors on behavior across generations and the plasticity of the epigenome across life. PMID- 27277119 TI - Locomotor Stimulant and Rewarding Effects of Inhaling Methamphetamine, MDPV, and Mephedrone via Electronic Cigarette-Type Technology. AB - Although inhaled exposure to drugs is a prevalent route of administration for human substance abusers, preclinical models that incorporate inhaled exposure to psychomotor stimulants are not commonly available. Using a novel method that incorporates electronic cigarette-type technology to facilitate inhalation, male Wistar rats were exposed to vaporized methamphetamine (MA), 3,4 methylenedioxypyrovalerone (MDPV), and mephedrone (4-methylmethcathinone) in propylene glycol vehicle using concentrations ranging from 12.5 to 200 mg/ml. Rats exhibited increases in spontaneous locomotor activity, measured by implanted radiotelemetry, following exposure to methamphetamine (12.5 and 100 mg/ml), MDPV (25, 50, and 100 mg/ml), and mephedrone (200 mg/ml). Locomotor effects were blocked by pretreatment with the dopamine D1-like receptor antagonist SCH23390 (10 MUg/kg, intraperitoneal (i.p.)). MA and MDPV vapor inhalation also altered activity on a running wheel in a biphasic manner. An additional group of rats was trained on a discrete trial intracranial self-stimulation (ICSS) procedure interpreted to assess brain reward status. ICSS-trained rats that received vaporized MA, MDPV, or mephedrone exhibited a significant reduction in threshold of ICSS reward compared with vehicle. The effect of vapor inhalation of the stimulants was found comparable to the locomotor and ICSS threshold-reducing effects of i.p. injection of mephedrone (5.0 mg/kg), MA (0.5-1.0 mg/kg), or MDPV (0.5-1.0 mg/kg). These data provide robust validation of e-cigarette-type technology as a model for inhaled delivery of vaporized psychostimulants. Finally, these studies demonstrate the potential for human use of e-cigarettes to facilitate covert use of a range of psychoactive stimulants. Thus, these devices pose health risks beyond their intended application for the delivery of nicotine. PMID- 27277121 TI - Measurement of shear wave propagation and investigation of estimation of shear viscoelasticity for tissue characterization of the arterial wall. AB - PURPOSE: The aim of this study was to find an array of frequency components, ranging from 0 Hz (direct current) to several tens of hertz that comprise the small vibrations on the arterial wall using noninvasive in vivo experiments. These vibrations are caused mainly by blood flow. The viscoelasticity of the arterial wall was estimated from the frequency characteristics of these vibrations propagating from the intima to the adventitia. METHODS: Propagation of these frequencies in human tissue displays certain frequency characteristics. Based on the Voigt model, shear viscoelasticity can be estimated from the frequency characteristics of the propagating vibrations. Moreover, we estimated shear viscoelasticity from the measured frequency characteristics of shear wave attenuation. RESULTS: Shear wave propagation from the intima to the adventitia resulting from blood flow was explained theoretically based on the obtained measurements. Shear viscoelasticity was also estimated from the measured frequency characteristics of shear wave attenuation. CONCLUSIONS: Based on the proposed method, shear viscoelasticity can be estimated from ultrasonographic measurements. These results have a novel potential for characterizing tissue noninvasively. PMID- 27277122 TI - Differentiation of myocardial infarction and angina pectoris by processing ultrasonic color kinesis images. AB - PURPOSE: The aim of this study was to develop a method for early, accurate differentiation between old myocardial infarction (OMI) and angina pectoris (AP) using color kinesis (CK) images. We first extracted exact end-diastolic and end systolic contours from CK images and then extracted the features of cardiac function from two CK images (one at rest, the other after exercise) and investigated their effectiveness in differentiating old myocardial infarction and angina pectoris. We then evaluated the effectiveness of several features in recognizing coronary artery disease and used the effective features to show the differentiation results. METHODS: First, we extracted exact end-diastolic and end systolic contours from CK images with an active contour model. Second, we defined the features that seemed to be effective in recognizing coronary artery disease. The features are extracted from the region between the end-diastolic endocardial contour and end-systolic endocardial contour in two CK images: one obtained when the subject was at rest and the other after exercise. Nine features were considered effective for differentiating old myocardial infarction and angina pectoris, and the effectiveness in recognizing coronary artery disease, which includes old myocardial infarction and angina pectoris, was evaluated. Third, coronary artery disease is recognized by the effective features. RESULTS: Contours near a manual trace by a skilled physician were obtained using the proposed method. Multiple comparisons of the mean values of the extracted features were drawn among three groups: a healthy-subject group; an old myocardial infarction patient group; and an angina pectoris patient group. The feature effective in differentiating old myocardial infarction was the "area at rest"; those effective in differentiating angina pectoris were a "decrease in area" and a "decrease in movement." These effective features have almost always differentiated old myocardial infarction and angina pectoris. CONCLUSIONS: This study used the endocardial contour extraction technique with the dynamic contour model and evaluated the validity of the features of cardiac function; it then recognized coronary artery disease from the effective features. Multiple comparisons of the mean value of the extracted features among the healthy-subject group, the old myocardial infarction patient group, and the angina pectoris patient group has proved that the "area at rest" is effective in differentiating old myocardial infarction, and the "decrease in area" and "decrease in movement" are effective for differentiating angina pectoris. PMID- 27277124 TI - A case of unicuspid aortic valve associated with a single coronary artery and ventricular septal defect. AB - The patient was a 26-year-old man who had undergone patch closure of a ventricular septal defect at 2 years of age. After this surgery, his condition was satisfactory until he visited our hospital for treatment of paroxysmal supraventricular tachycardia in November 2000. Echocardiography revealed moderate to severe aortic valve regurgitation and dilatation of the left ventricle and ascending aorta. These echocardiographic abnormalities were attributed to a bicuspid aortic valve. Coronary angiography suggested the presence of a single coronary artery originating from the left Valsalva sinus. We performed Bentall's operation in January 2003. The intraoperative findings revealed that the aortic valve consisted of an extensively calcified single cusp, and there was a single coronary artery originating from the left Valsalva sinus. Because adult patients with a unicuspid aortic valve are rare, and no cases of unicuspid aortic valve associated with a single coronary artery have been reported, we herein report this case with a review of the literature. PMID- 27277123 TI - Contrast-enhanced multiphase dynamic ultrasonography for the characterization of liver tumors. AB - PURPOSE: The purpose of the study was to introduce our protocol for contrast enhanced multiphase dynamic ultrasonography (US) and examine the effectiveness of this method for characterizing liver tumors. METHODS: The subjects were 142 patients with liver tumors. The final diagnoses were 58 hepatocellular carcinomas (HCCs), 4 cholangiocellular carcinomas (CCCs), 14 metastases, 29 hemangiomas, 6 cases of focal nodular hyperplasia (FNH), and 31 other benign lesions. The contrast agent used was Levovist. A wide-band pulse inversion harmonic imaging mode was employed. Multiphase dynamic US was achieved by changing the sound transmission interval automatically from 0.3 s to 15.0 s according to a preset menu. Early arterial-phase images were observed at the short interval, and an equilibrium-phase image was observed at the longest interval. After a series of vascular images, a postvascular liver parenchymal image was obtained. Based on previously published criteria, the most compatible diagnosis was noted. The accuracy of this multiphase dynamic US technique for diagnosing focal liver lesions was examined by comparing our results with the final diagnosis based on a prospective study. RESULTS: The overall accuracy of all 142 cases was 93.7%. The sensitivity, specificity, and positive predictive value were, respectively, 100%, 92.9%, and 90.6% for HCC; 88.9%, 97.6%, and 84.2% for metastasis or CCC; 89.7%, 100%, and 100% for hemangioma; and 83.3%, 100%, and 100% for FNH. CONCLUSION: Contrast-enhanced multiphase dynamic US is a highly accurate, safe diagnostic tool for characterizing liver tumors. PMID- 27277125 TI - Benign endometrial adenofibroma and polyp in patients receiving tamoxifen: findings on transvaginal ultrasonography and magnetic resonance imaging. AB - Tamoxifen, a selective estrogen receptor modulator, is widely used to treat breast cancer, but an association has been reported between tamoxifen and the development of endometrial lesions, including endometrial carcinoma, endometrial polyps, and endometrial hyperplasia. There have also recently been a few reports on the relation between tamoxifen and adenofibroma. We present two case reports, one of a patient with a uterine adenofibroma and one of a patient with an endometrial polyp, both of whom received tamoxifen. Cases 1 and 2 are 75- and 65 year-old postmenopausal women, respectively, undergoing tamoxifen therapy. In both cases, endometrial thickening and many small cysts in the uterine cavity were revealed by transvaginal ultrasonography or magnetic resonance imaging. Postoperative microscopic examination confirmed the mass as an adenofibroma in case 1 and as an endometrial polyp in case 2. PMID- 27277127 TI - Standard measurement of cardiac function indexes (proposal). PMID- 27277126 TI - Wall thickening of the common carotid artery that increased over a 15-month period. PMID- 27277128 TI - Biolistic transformation of Carrizo citrange (Citrus sinensis Osb. * Poncirus trifoliata L. Raf.). AB - KEY MESSAGE: The development of transgenic citrus plants by the biolistic method. A protocol for the biolistic transformation of epicotyl explants and transgenic shoot regeneration of immature citrange rootstock, cv. Carrizo (Citrus sinensis Osb. * Poncirus trifoliata L. Raf.) and plant regeneration is described. Immature epicotyl explants were bombarded with a vector containing the nptII selectable marker and the gfp reporter. The number of independent, stably transformed tissues/total number of explants, recorded by monitoring GFP fluorescence 4 weeks after bombardment was substantial at 18.4 %, and some fluorescing tissues regenerated into shoots. Fluorescing GFP, putative transgenic shoots were micro grafted onto immature Carrizo rootstocks in vitro, confirmed by PCR amplification of nptII and gfp coding regions, followed by secondary grafting onto older rootstocks grown in soil. Southern blot analysis indicated that all the fluorescing shoots were transgenic. Multiple and single copies of nptII integrations were confirmed in five regenerated transgenic lines. There is potential to develop a higher throughput biolistics transformation system by optimizing the tissue culture medium to improve shoot regeneration and narrowing the window for plant sampling. This system will be appropriate for transformation with minimal cassettes. PMID- 27277129 TI - Preimplantation Genetic Diagnosis (PGD) for Monogenic Disorders: the Value of Concurrent Aneuploidy Screening. AB - Pre-implantation genetic diagnosis (PGD) has changed the landscape of clinical genetics by helping families reduce the transmission of monogenic disorders. However, given the high prevalence of embryonic aneuploidy, particularly in patients of advanced reproductive age, unaffected embryos remain at high risk of implantation failure or pregnancy loss due to aneuploidy. 24-chromosome aneuploidy screening has become widely utilized in routine in vitro fertilization (IVF) to pre-select embryos with greater pregnancy potential, but concurrent 24 chromosome aneuploidy screening has not become standard practice in embryos biopsied for PGD. We performed a retrospective cohort study of patients who underwent PGD with or without 24-chromosome aneuploidy screening to explore the value of concurrent screening. Among the PGD + aneuploidy-screened group (n = 355 blastocysts), only 25.6 % of embryos were both Single Gene Disorder (SGD) negative (or carriers) and euploid; thus the majority of embryos were ineligible for transfer due to the high prevalence of aneuploidy. Despite a young mean age (32.4 +/- 5.9y), 49.9 % of Blastocysts were aneuploid. The majority of patients (53.2 %) had >=1 blastocyst that was Single Gene Disorder (SGD)-unaffected but aneuploid; without screening, these unaffected but aneuploid embryos would likely have been transferred resulting in implantation failure, pregnancy loss, or a pregnancy affected by chromosomal aneuploidy. Despite the transfer of nearly half the number of embryos in the aneuploidy-screened group (1.1 +/- 0.3 vs. 1.9 +/- 0.6, p < 0.0001), the implantation rate was higher (75 % vs. 53.3 %) and miscarriage rate lower (20 % vs. 40 %) (although not statistically significant). 24-chromosome aneuploidy screening when performed concurrently with PGD provides valuable information for embryo selection, and notably improves single embryo transfer rates. PMID- 27277130 TI - "The Top Priority Is a Healthy Baby": Narratives of Health, Disability, and Abortion in Online Pregnancy Forum Discussions in the US and China. AB - The introduction of cell-free DNA prenatal genetic screening has rekindled discussion of ethical and social questions surrounding prenatal testing, perceptions of disability, and abortion. The growing use of prenatal genetic screening presents a unique opportunity to assess decision-making around new methods of prenatal testing; especially as there is little available research comparing individual and cultural differences that affect a pregnant woman's decision-making on prenatal testing. We performed a content analysis of online pregnancy forums in the United States and Mainland China. Content from January 2012 to December 2013 was identified through search methodologies and refined to remove duplication. China-based content was translated by a native Mandarin speaker. We used qualitative analysis methods to identify common themes in the dataset. There were 333 English responses and 519 Mandarin responses. Three main themese were identified in the data: decision making factors, attitude towards the pregnancy, and attitudes towards abortion. Women's narratives reflected how broader social forces can have an impact on intimate personal decision-making. Women in the Mandarin dataset evoked stronger narratives of community and/or family decision-making in pregnancy and were more accepting of the possibility of abortion in the event of a finding of fetal abnormality. Narrative in the English dataset more frequently evoked ideas of unconditional love, regardless of fetal diagnosis, but also acknowledged much stronger support services for individuals with disability and less awareness of stigma. These results highlight the necessity of awareness around how broader cultural and social factors can consciously or unconsciously impact women's decisions and highlight potential focus areas for future counseling efforts. PMID- 27277131 TI - Attitudes Toward Discussing Approved and Investigational Treatments for Cystic Fibrosis in Prenatal Genetic Counseling Practice. AB - This project aimed to explore the attitudes of prenatal genetic counselors toward discussion of novel approved and experimental CF treatments in the prenatal setting, and to assess how knowledge of genotype-specific, targeted treatments may influence their current practices. Targeted treatments have the potential to impact the health-related quality of life of individuals affected with CF and therefore, knowledge of the availability of such treatments may influence the decision-making process of parents who receive a fetal diagnosis of CF. Using the 2012 FDA approval and introduction of ivacaftor into CF clinical practice as a case study, a survey was designed to explore the opinions and practices of prenatal genetic counselors with regard to counseling for a prenatal diagnosis of CF, and how those practices might be impacted by the availability of a new genotype-specific treatment. Approximately 800 genetic counselors were sent questionnaires in January of 2013. Respondents were provided information about this treatment and were asked to rate its perceived benefits, along with the likelihood that they would discuss potential benefits and limitations with parents receiving a prenatal diagnosis of CF. One-hundred sixty-nine prenatal genetic counselors (21.1 %) responded to the survey. Results indicated that 80 % of respondents 'never heard of the drug', or they were 'not exactly sure' what it was. After reading the materials provided, counselors felt the new treatment would have 'some' or a 'significant' impact on an affected individual's life. Their opinions varied on what information about this treatment they would choose to discuss with their patients; even if the treatment is currently FDA approved and clinically available for affected individuals with the genotype of the fetus. However, they would 'definitely' refer these patients to a specialist to discuss targeted treatments further. Most prenatal genetic counselors indicated there are certain scenarios in the prenatal setting which warrant a discussion of targeted treatments for CF, at least on some level. Counselor's views on sharing information about new treatment options are shaped by their familiarity with the treatment and their perception of its benefits and limitations, their comfort discussing these subjects, and their interpretation of the genetic counselor's role. Most genetic counselors had never heard of ivacaftor or KalydecoTM prior to taking the survey. Therefore, counselors need to be better educated about the availability of CFTR mutation-based treatments before they will be able to incorporate discussion of new treatment options into their counseling. PMID- 27277132 TI - Atopy and Specific Cancer Sites: a Review of Epidemiological Studies. AB - Mounting evidence appears to link asthma and atopy to cancer susceptibility. This review presents and discusses published epidemiological studies on the association between site-specific cancers and atopy. PubMed was searched electronically for publications between 1995 and 2015, and cited references were researched manually. Quantitative studies relating to atopy, allergy, or asthma and cancer were identified and tabulated. Despite many exposure-related limitations, patterns in the studies were observed. Asthma, specifically, has been observed to be a risk factor for lung cancer. A protective effect of atopic diseases against pancreatic cancer has been shown consistently in case-control studies but not in cohort studies. Allergy of any type appears to be protective against glioma and adult acute lymphoblastic leukemia. Most studies on atopic diseases and non-Hodgkin lymphoma or colorectal cancer reported an inverse association. The other sites identified had varying and non-significant outcomes. Further research should be dedicated to carefully defined exposure assessments of "atopy" as well as the biological plausibility in the association between atopic diseases and cancer. PMID- 27277133 TI - Diagnoses and Management of Drug Hypersensitivity and Anaphylaxis in Cancer and Chronic Inflammatory Diseases: Reactions to Taxanes and Monoclonal Antibodies. AB - Due to the increase in utilization of chemotherapies and antibodies, drug hypersensitivity reactions have increased dramatically worldwide, preventing the use of first-line therapies and impacting patients' survival and quality of life. Some of the more frequently used medications in cancer include taxanes for ovarian, lung, breast, and prostate cancers. Monoclonal antibodies are used in the treatment of neoplastic, autoimmune, and inflammatory diseases, and their clinical applications are becoming broader. Monoclonal antibody targets include CD20, HER-2, EGFR, IL-6 receptor, TNF-alpha, CD30, VEGF-A, IgE, and more, and examples of immune-mediated and inflammatory diseases that respond to monoclonal antibodies include rheumatoid arthritis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, psoriasis and psoriatic arthritis, Wegener's granulomatosis, microscopic polyangiitis, ankylosing spondylitis, plaque psoriasis, and asthma. Neoplastic diseases include non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and colorectal, breast, gastric, and lung cancer. The clinical presentation of drug hypersensitivity reactions ranges from mild cutaneous reactions to life-threatening symptoms including anaphylaxis. Rapid drug desensitization (RDD) has become a groundbreaking approach to the management of immediate drug hypersensitivity reactions IgE and non-IgE mediated. It is the only effective procedure that enables sensitized patients to receive the full treatment dose safely, thus representing an important advance in the patients' treatment and prognosis. The aim of this review is to provide an update on hypersensitivity reactions to commonly used monoclonal and taxanes, their clinical presentations, diagnosis, and the use of RDD for their management. PMID- 27277134 TI - Characterization of the microbial community composition and the distribution of Fe-metabolizing bacteria in a creek contaminated by acid mine drainage. AB - A small watershed heavily contaminated by long-term acid mine drainage (AMD) from an upstream abandoned coal mine was selected to study the microbial community developed in such extreme system. The watershed consists of AMD-contaminated creek, adjacent contaminated soils, and a small cascade aeration unit constructed downstream, which provide an excellent contaminated site to study the microbial response in diverse extreme AMD-polluted environments. The results showed that the innate microbial communities were dominated by acidophilic bacteria, especially acidophilic Fe-metabolizing bacteria, suggesting that Fe and pH are the primary environmental factors in governing the indigenous microbial communities. The distribution of Fe-metabolizing bacteria showed distinct site specific patterns. A pronounced shift from diverse communities in the upstream to Proteobacteria-dominated communities in the downstream was observed in the ecosystem. This location-specific trend was more apparent at genus level. In the upstream samples (sampling sites just below the coal mining adit), a number of Fe(II)-oxidizing bacteria such as Alicyclobacillus spp., Metallibacterium spp., and Acidithrix spp. were dominant, while Halomonas spp. were the major Fe(II) oxidizing bacteria observed in downstream samples. Additionally, Acidiphilium, an Fe(III)-reducing bacterium, was enriched in the upstream samples, while Shewanella spp. were the dominant Fe(III)-reducing bacteria in downstream samples. Further investigation using linear discriminant analysis (LDA) effect size (LEfSe), principal coordinate analysis (PCoA), and unweighted pair group method with arithmetic mean (UPGMA) clustering confirmed the difference of microbial communities between upstream and downstream samples. Canonical correspondence analysis (CCA) and Spearman's rank correlation indicate that total organic carbon (TOC) content is the primary environmental parameter in structuring the indigenous microbial communities, suggesting that the microbial communities are shaped by three major environmental parameters (i.e., Fe, pH, and TOC). These findings were beneficial to a better understanding of natural attenuation of AMD. PMID- 27277135 TI - Non-traumatic lower limb amputation in patients with end-stage renal failure on dialysis: an Australian perspective. AB - BACKGROUND: End-stage renal failure (ESRF) and dialysis have been identified as a risk factor for lower limb amputations (LLAs). High rate of ESRF amongst the Australian population has been reported, however till date no study has been published identifying magnitude and risk factors of LLA in subjects on renal dialysis. OBJECTIVE: The study aims to document trends in the prevalence and identify risk factors of non-traumatic LLA in Australian patients on dialysis. METHODS: A retrospective review of all patients (218) who attended the regional dialysis center between 1st January 2009 and 31st December 2013 was conducted. Demographic, clinical and biochemical data were analyzed. RESULTS: We identified a high prevalence of 13.3% of LLAs amongst Australian patients with ESRF on dialysis at our center. The associated risk factors were the presence of diabetes (OR 1.67 [1.49-1.88] p < 0.001), history of foot ulceration (OR 81 [18.20-360.48] p < 0.001), peripheral arterial disease (OR 31.29 [9.02-108.56] p < 0.001), peripheral neuropathy (OR 31.29 [9.02-108.56] p < 0.001), foot deformity (OR 23.62 [5.82-95.93] p < 0.001), retinopathy (OR 6.08 [2.64-14.02] p < 0.001), dyslipidemia (OR 4.6 [1.05-20.05] p= 0.049) and indigenous background (OR 3.39 [1.38-8.33] p= 0.01). 75% of the amputees had aboriginal heritage. We also identified higher HbA1c and CRP levels as well as low serum albumin, hemoglobin and vitamin D levels to have a strong association with LLAs (p < 0.05). CONCLUSION: There is high prevalence of LLAs amongst Australian indigenous patients with diabetes on dialysis in North Queensland. Other strongly associated risk factors include history of foot ulceration, foot deformity and peripheral neuropathy as well as high HbA1c levels and low serum albumin levels. PMID- 27277136 TI - Assessment of Time to Clinical Response in Patients with Sepsis Treated Before and After Implementation of a Matrix-Assisted Laser Desorption Ionization Time-of Flight Blood Culture Identification Algorithm. AB - OBJECTIVE To evaluate time to clinical response before and after implementation of rapid blood culture identification technologies. DESIGN Before-and-after trial. SETTING Large, tertiary, urban, academic health-sciences center. PATIENTS Patients >18 years old with sepsis and concurrent bacteremia or fungemia were included in the study; patients who were pregnant, had polymicrobial septicemia, or were transferred from an outside hospital were excluded. INTERVENTION Prior to the intervention, polymerase chain reaction was used to identify Staphylococcus species from positive blood cultures, and traditional laboratory techniques were used to identify non-staphylococcal species. After the intervention, matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) assay and FilmArray were also used to identify additional species. During both periods, the antimicrobial stewardship team provided prospective audit and feedback for all patients on antibiotics. RESULTS A total of 219 patients were enrolled in the study: 115 patients prior to the intervention and 104 after the intervention. The median time to clinical response was statistically significantly shorter in the postintervention group than in the preintervention group (2 days vs 4 days, respectively; P=.002). By Cox regression, the implementation of MALDI-TOF and FilmArray was associated with shorter time to clinical response (hazard ratio [HR], 1.360; 95% confidence interval [CI], 1.018-1.816). After controlling for potential confounders, the study group was not independently associated with clinical response (adjusted HR, 1.279; 95% CI, 0.955-1.713). Mortality was numerically, but not statistically significantly, lower in the postintervention group than in the preintervention group (7.6% vs 11.4%; P=.342). CONCLUSIONS In the setting of an existing antimicrobial stewardship program, implementation of MALDI-TOF and FilmArray was associated with improved time to clinical response. Further research is needed to fully describe the effect of antimicrobial stewardship programs on time to clinical response. Infect Control Hosp Epidemiol 2016;37:916-923. PMID- 27277137 TI - Geraniol Induces Antinociceptive Effect in Mice Evaluated in Behavioural and Electrophysiological Models. AB - Geraniol (GER) is a monoterpene alcohol with various biochemical and pharmacological properties present in the essential oil of more than 160 species of herbs (especially the Cymbopogon genus). In this study, we evaluated the antinociceptive activity of GER in behavioural and electrophysiological in vitro experimental models of nociception using male Swiss mice. GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) reduced the number of writhes induced by acetic acid. The opioid antagonist naloxone (5 mg/kg s.c.) administered in mice subsequently treated with GER (25 mg/kg i.p.) did not reverse such antinociceptive activity, suggesting a non-opioid pathway for the mechanism of action. GER (12.5, 25 and 50 mg/kg i.p.) reduced paw licking time in the second phase of the formalin test. Also, in the glutamate test, GER when administered 50 mg/kg i.p. reduced paw licking time, probably modulating glutamatergic neurotransmission. GER blocked reversibly components of the compound action potential (CAP) recorded in isolated sciatic nerve in a concentration- and drug exposure time-dependent manner: 1 mM to 120 min. for the first component and 0.6 mM to 90 min. for the second component. The IC50 was calculated for the peak-to peak amplitude (PPA) at 0.48 +/- 0.04 mM. The conduction velocity was also reduced by exposure to GER starting from the concentration of 0.3 mM for both components of the CAP. In conclusion, it is suggested that GER has antinociceptive activity, especially in pain related to inflammation, and in part related to reduced peripheral nerve excitability. PMID- 27277138 TI - Evolution and Use of Dynamic Transmission Models for Measles and Rubella Risk and Policy Analysis. AB - The devastation caused by periodic measles outbreaks motivated efforts over more than a century to mathematically model measles disease and transmission. Following the identification of rubella, which similarly presents with fever and rash and causes congenital rubella syndrome (CRS) in infants born to women first infected with rubella early in pregnancy, modelers also began to characterize rubella disease and transmission. Despite the relatively large literature, no comprehensive review to date provides an overview of dynamic transmission models for measles and rubella developed to support risk and policy analysis. This systematic review of the literature identifies quantitative measles and/or rubella dynamic transmission models and characterizes key insights relevant for prospective modeling efforts. Overall, measles and rubella represent some of the relatively simplest viruses to model due to their ability to impact only humans and the apparent life-long immunity that follows survival of infection and/or protection by vaccination, although complexities arise due to maternal antibodies and heterogeneity in mixing and some models considered potential waning immunity and reinfection. This review finds significant underreporting of measles and rubella infections and widespread recognition of the importance of achieving and maintaining high population immunity to stop and prevent measles and rubella transmission. The significantly lower transmissibility of rubella compared to measles implies that all countries could eliminate rubella and CRS by using combination of measles- and rubella-containing vaccines (MRCVs) as they strive to meet regional measles elimination goals, which leads to the recommendation of changing the formulation of national measles-containing vaccines from measles only to MRCV as the standard of care. PMID- 27277139 TI - Adaptive evolution and functional innovation of Populus-specific recently evolved microRNAs. AB - Lineage-specific microRNAs (miRNAs) undergo rapid turnover during evolution; however, their origin and functional importance have remained controversial. Here, we examine the origin, evolution, and potential roles in local adaptation of Populus-specific miRNAs, which originated after the recent salicoid-specific, whole-genome duplication. RNA sequencing was used to generate extensive, comparable miRNA and gene expression data for six tissues. A natural population of Populus trichocarpa and closely related species were used to study the divergence rates, evolution, and adaptive variation of miRNAs. MiRNAs that originated in 5' untranslated regions had higher expression levels and their expression showed high correlation with their host genes. Compared with conserved miRNAs, a significantly higher proportion of Populus-specific miRNAs appear to target genes that were duplicated in salicoids. Examination of single nucleotide polymorphisms in Populus-specific miRNA precursors showed high amounts of population differentiation. We also characterized the newly emerged MIR6445 family, which could trigger the production of phased small interfering RNAs from NAC mRNAs, which encode a transcription factor with primary roles in a variety of plant developmental processes. Together, these observations provide evolutionary insights into the birth and potential roles of Populus-specific miRNAs in genome maintenance, local adaptation, and functional innovation. PMID- 27277140 TI - Differential proteomics profiling of the ova between healthy and Rice stripe virus-infected female insects of Laodelphax striatellus. AB - Rice stripe virus-infected females of the small brown planthopper (SBPH, Laodelphax striatellus) usually lay fewer eggs with a longer hatch period, low hatchability, malformation and retarded or defective development compared with healthy females. To explore the molecular mechanism of those phenomena, we analyzed the differential proteomics profiling of the ova between viruliferous and healthy female insects using an isobaric tag for relative and absolute quantitation (iTRAQ) approach. We obtained 147 differentially accumulated proteins: 98 (66.7%) proteins increased, but 49 (33.3%) decreased in the ova of the viruliferous females. RT-qPCR was used to verify the 12 differential expressed proteins from iTRAQ, finding that trends in the transcriptional change for the 12 genes were consistent with those at the proteomic level. Differentially expressed proteins that were associated with meiosis (serine/threonine-protein phosphatase 2B and cyclin B3) and mitosis (cyclin B3 and dynein heavy chain) in viruliferous ova may contribute to low hatchability and defective or retarded development. Alterations in the abundance of proteins involved in the respiratory chain and nutrition metabolism may affect embryonic development. Our study begins to explain macroscopical developmental phenomena and explore the mechanisms by which Rice stripe virus impacts the development of SBPH. PMID- 27277142 TI - Corrigendum. PMID- 27277141 TI - An Epichloe festucae homologue of MOB3, a component of the STRIPAK complex, is required for the establishment of a mutualistic symbiotic interaction with Lolium perenne. AB - In both Sordaria macrospora and Neurospora crassa, components of the conserved STRIPAK (striatin-interacting phosphatase and kinase) complex regulate cell-cell fusion, hyphal network development and fruiting body formation. Interestingly, a number of Epichloe festucae genes that are required for hyphal cell-cell fusion, such as noxA, noxR, proA, mpkA and mkkA, are also required for the establishment of a mutualistic symbiotic interaction with Lolium perenne. To determine whether MobC, a homologue of the STRIPAK complex component MOB3 in S. macrospora and N. crassa, is required for E. festucae hyphal fusion and symbiosis, a mobC deletion strain was generated. The DeltamobC mutant showed reduced rates of hyphal cell cell fusion, formed intrahyphal hyphae and exhibited enhanced conidiation. Plants infected with DeltamobC were severely stunted. Hyphae of DeltamobC showed a proliferative pattern of growth within the leaves of Lolium perenne with increased colonization of the intercellular spaces and vascular bundles. Although hyphae were still able to form expressoria, structures allowing the colonization of the leaf surface, the frequency of formation was significantly reduced. Collectively, these results show that the STRIPAK component MobC is required for the establishment of a mutualistic symbiotic association between E. festucae and L. perenne, and plays an accessory role in the regulation of hyphal cell-cell fusion and expressorium development in E. festucae. PMID- 27277144 TI - Pregnancy and lactation period: Which antibiotic and rinsing solutions? AB - The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and rinsing solutions. Antibiotics as penicillins are the first choice in case of dental infections in pregnancy. In allergic patients, macrolides may be an alternative. Wound and mouth rinsing solutions containing chlorhexidine should be preferred in pregnancy. Ledermix((r)) in endodontic treatment should be avoided in the pregnant woman. Solcoseryl((r)) can be used for wound healing. Elective dental procedures should be postponed after delivery and after lactation period. PMID- 27277145 TI - A political construction or a coincidence? PMID- 27277143 TI - SIRT3 participates in glucose metabolism interruption and apoptosis induced by BH3 mimetic S1 in ovarian cancer cells. AB - The Bcl-2 antiapoptotic proteins are important cancer therapy targets; however, their role in cancer cell metabolism remains unclear. We found that the BH3-only protein mimetic S1, a novel pan Bcl-2 inhibitor, simultaneously interrupted glucose metabolism and induced apoptosis in human SKOV3 ovarian cancer cells, which was related to the activation of SIRT3, a stress-responsive deacetylase. S1 interrupted the cellular glucose metabolism mainly through causing damage to mitochondrial respiration and inhibiting glycolysis. Moreover, S1 upregulated the gene and protein expression of SIRT3, and induced the translocation of SIRT3 from the nucleus to mitochondria. SIRT3 silencing reversed the effects of S1 on glucose metabolism and apoptosis through increasing the level of HK-II localized to the mitochondria, while a combination of the glycolysis inhibitor 2-DG and S1 intensified the cytotoxicity through further upregulation of SIRT3 expression. This study underscores an essential role of SIRT3 in the antitumor effect of Bcl 2 inhibitors in human ovarian cancer through regulating both metabolism and apoptosis. The manipulation of Bcl-2 inhibitors combined with the use of classic glycolysis inhibitors may be rational strategies to improve ovarian cancer therapy. PMID- 27277146 TI - Prolonged stays in hospital acute geriatric care units: identification and analysis of causes. AB - In France, the population of very old frail patients, who require appropriate high-quality care, is increasing. Given the current economic climate, the mean duration of hospitalization (MDH) needs to be optimized. This prospective study analyzed the causes of prolonged hospitalization in an acute geriatric care unit. Over 6 months, all patients admitted to the target acute geriatric care unit were included and distributed into two groups according to a threshold stay of 14 days: long MDH group (LMDHG) and short MDH group (SMDHG). These two groups were compared. 757 patients were included. The LMDHG comprised 442 with a mean age of 86.7 years, of whom 67.65% were women and the SMDHG comprised 315 with a mean age of 86.6 years, of whom 63.2% were women. The two groups were statistically similar for age, sex, living conditions at home (alone or not, help), medical history and number of drugs. Patients in the LMDHG were more dependent (p=0.005), and were more likely to be hospitalized for social reasons (p=0.024) and to have come from their homes (p=0.011) than those in the SMDHG. The reasons for the prolonged stay, more frequent in the LMDHG than the SMDHG (p<0.05), were principally: waiting for imaging examinations, medical complications, and waiting for discharge solutions, assistance from social workers and/or specialist consultations. In order to reduce the MDH in acute geriatric care unit, it is necessary to consider the particularities of the patients who are admitted, their medico-socio-psychological management, access to technical facilities/consultations and post-discharge accommodation. PMID- 27277147 TI - Treatment in idiopathic thrombocytopenic purpura in the elderly: about a retrospective study. AB - There are no specific recommendations on the care of elderly patients with ITP. A retrospective study over two academic centers (Reims and Strasbourg), focused on patients over 65 who have been diagnosed idiopathic thrombocytopenic purpura in two unit of internal medicine. 41 patients were enrolled, including 27 women (66%). The median age is 76.75 years. On admission, the average thrombocytopenia is 34.45 G/L; 24 patients (58.5%) showed severe bleeding mucosal and/or visceral signs; 37 patients (90%) had a first-line treatment. Corticosteroids established for 23 patients (56%). At 1 and 6 months, complete response was 9 patients (39%) and 2 patients (9%) respectively. Adverse events reported for 20 patients (87%). Polyvalent immunoglobulins were used for 6 (16%) with no response at 6 months. 5 patients were treated with danazol. At 6 months, partial response in 3 patients (60%) and failure in 2 patients (40%). Splenectomy was performed for 8 patients (21%). At 1 month, a complete response observed for 7 patients. At 6 months, a failure observed in 4 patients. After failure of first-line treatments, we noted the use of rituximab for 4 patients (9.7%) with a complete response for 1 patient, partial response in 2 patients and a failure for a patient for whom the "eltrombopag" was set up with a partially response. Monitoring of 41 patients, during 7 years, objectified 3 deaths. The clinical presentation of idiopathic thrombocytopenic purpura in the elderly seems more severe. Therapeutic responses are essentially identical to those observed in younger patients, but greater toxicity. Data on biologics is nonexistent in elderly outside small retrospective series. Studies are underway to better assess their effectiveness, long-term safety as well as their mechanism of action. PMID- 27277148 TI - Difficulties encountered by general practitioners during acute behavioral disturbances of their dementia patients. AB - Alzheimer diseases and related disorders (ADRD) remain a major public health issue. The progression of the disease is dominated by behavioral and psychological symptoms of dementia (BPSD) which are frequent and burdensome for caregivers. The aim of our survey was to study how the general practionner managed these behavioral disturbances (particularly agitation and aggressiveness) in community living patients with ADRD and support of their main caregivers. We based our study on a medical survey sent to all general practitioners (GP) practicing in four districts in Marseille near from a secure unit. Ninety five out of 260 answered to the survey and 57 had already been exposed to patients' behavioral decompensation. For these BPSD management, atypical neuroleptics and benzodiazepines were mostly prescribed, and according to the literature and guidelines. Half of the GP's recognized the weak effectiveness of this strategy. Almost all of them are interested in having a document summarizing the main strategy to be set up or a possibility to call a specialized mobile team with doctors and professionals caregivers. A few dedicated consultations were devoted to informal caregivers whereas GP were aware of negative effects of these decompensations on them. This study point out difficulties for GP to provide appropriate management for their patients with ADRD living at home and for their informal caregivers, particularly during acute behavioral disturbance, despite their practical knowledges. PMID- 27277149 TI - Editorial. PMID- 27277150 TI - Ageism and overestimation of cognitive difficulties in older people: a review. AB - Stigmatization related to age (i.e., ageism) is a widespread phenomenon in the modern industrial societies where older people are perceived as cognitively incompetent. Therefore negative stereotypes about age-related cognitive decline may have a detrimental influence on older adults on their cognitive performance. The aim of the present review is to understand how stereotypes can influence the performance of the elderly on cognitive tests. We first describe the stereotype threat phenomenon by providing an overview of situations likely to produce stereotype threat, as well as contextual and personal characteristics that moderate its effects. Possible mechanisms underlying these influences on cognitive performance are also presented. Secondly, we address self-stereotyping, which explains long-term negative effects of stereotypes and their unconscious influence on older adults' cognitive performance. However, some age stereotypes have also positive effects on aged people, as shown by some studies describing such beneficial effects of positive stereotypes on cognitive performance. Finally we try to understand why negative age stereotyping has a much stronger influence on important behavioral outcomes among older adults than does positive age stereotyping. Given all these results, we examine how negative age stereotypes may impact older adults' cognitive performance in real-world settings such as during a cognitive assessment. PMID- 27277151 TI - Alcoholic abstinence in elderly subjects with misuse of alcohol. AB - Alcohol use disorder does not disappear with aging, neither the associated induced-suffering. While the prevalence of alcohol use disorder still remains around 10% in the subjects over 65 year old age, and daily encountered by hospital or nursing-home caregivers. Alcohol misuse is often overlooked in elderly people, which then obtain lesser care than younger adults although the care prognosis remains as good as or better than before the age of 65, alcoholic abstinence gets always a place among care offers to elders suffering of alcohol use disorders and dependence. However abstinence is a complex notion gathering various representations or meanings, and induces necessary psychological changes. Alcoholic abstinence seems thus to be feared by families or caregivers, because of lack of knowledge about the addictive dimension of the disorder. On behalf of ultimate freedom, and allowing a last pleasure, alcohol use disorders and its associated suffering can be neglected because abstinence is considered as aggressive and harmful. However, modalities of reduction of alcohol consumption as well as access control or regulated supply of alcoholic beverages, keep having a place in graduate care offers. Beyond the choice of decreasing or suppress drinking alcohol beverages, which only are terms or conditions of improvement, the main point remains the improvement of well-fare, quality of life and elders' health. PMID- 27277152 TI - Young onset demented patients in French cognitive-behavioral specialized units. AB - The number of patients with young onset dementia (YOD) (first symptoms beginning before the age of 60 years) is estimated around 5,000 in France. On account of the usual severity of behavioral symptoms in these patients, the need for cognitive-behavioral specialized unit (UCC) is expected. To determine the number and characteristics of YOD patients cared for in UCC in France during the year 2013. A specific questionnaire was sent to the 84 French UCC. The questionnaire was completed by 55 UCC (65%), whose 33 received 179 YOD patients. The diagnosis was Alzheimer's disease in 50% of the cases and frontotemporal dementia in 30%. The main reasons for the hospitalization in UCC were the severity of behavioral symptoms in 86% of cases, the need to alleviate the caregiver burden in 31% and the waiting for a place in a nursing home in 23%. Mean duration of hospitalization was 40.4 +/- 20.5 days. At the end of hospitalization 51% of the patients returned to their original living accomodation and 39% entered into a nursing home. The main reason of YOD patients hospitalization reject was the care team's fear in the UCC without experience. The severity of the behavioral troubles was the major issue while the necessary ethical reflection raised by the YOD patients management was a positive aspect. The teams rated how ready do they feel about taking care of YOD patients on a scale from 0 to 100, the median was 35. The welcoming of YOD patients in UCC is necessary, however the severity of the behavioral troubles and the care teams fear prompt to set up specific education and to increase of the number of staff for YOD patients management. PMID- 27277153 TI - Time perception in patients with dementia with Lewy bodies. AB - Disturbances of time perception could explain some behavioral disorders in patients with dementia with Lewy bodies (DLB), and the aim of this preliminary study was to evaluate time perception in these patients. 7 patients with DLB (mean age = 82+/-6,8 years) were compared to 7 cognitively normal subjects (m = 81.2+/-6,8 years) for spatiotemporal orientation, verbal estimation, semantic knowledge, rhythm perception and verbal time estimation. The scores on the semantic scale of temporality were statistically different between the two groups, and patients made more rhythm errors than the control sample. Moreover, a significant improvement between the first and second assessment on verbal time estimation was found in the control subjetcs but not in the patients. Time perception seems to be disturbed in patients with DLB, but more studies are required to understand this result with the behavioural disorders. PMID- 27277154 TI - Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging. AB - Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed. PMID- 27277156 TI - Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression. AB - Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP-1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP-1 cells were differentiated to macrophages by phorbol 12 myristate 13-acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription-quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme-linked immunosorbent assay. IRF5 protein and nuclei co-localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN-gamma stimulation-induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels. PMID- 27277158 TI - Echocardiographically Derived Pulse Wave Velocity and Diastolic Dysfunction Are Associated with an Increased Incidence of Atrial Fibrillation in Patients with Systolic Heart Failure. AB - BACKGROUND: Chronic heart failure (CHF) is an established risk factor of atrial fibrillation (AF), but the prognostic value of cardiac and hemodynamic parameters in assessing the risk of developing AF among patients with CHF is less defined. METHODS AND RESULTS: We followed an outpatients cohort of CHF patients secondary to left ventricular (LV) systolic dysfunction, who were free of AF at baseline. All patients underwent clinical evaluation, comprehensive echocardiography, and blood drawing in the same morning. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was determined by Doppler echocardiography. A total of 77 patients (age 63 +/- 9 years; 79% male) with mean LVEF (34 +/- 8%) formed the study population. Fifteen patients developed incidental AF. At baseline, CHF patients who developed AF during follow-up had higher E-wave velocity (75 +/- 2 cm/sec vs. 60 +/- 2 cm/sec; P = 0.02), higher difference duration between mitral and pulmonary vein A velocity (A'-A), (10 +/- 35 msec vs. 43 +/- 44 msec P = 0.02), aPWV (7.1 +/- 2.6 vs. 5.3 +/- 1.9 m/sec P = 0.004), and furosemide dosage (110 +/- 145 mg vs. 49 +/- 48 mg P = 0.01) than those remaining free from AF. The two groups of patients did not significantly differ in terms of NYHA, LV volumes, ejection fraction, left atrial volume, creatinine, hemoglobin, renin, epinephrine, amino-terminal propeptide of type III and I procollagens, ACE inhibitor, and beta-blocker dose (P > 0.1 for all). Notably, higher aPWV (P = 0.01) and longer A-A' duration (P = 0.04) were associated with an increased incidence of AF, independently of potential confounders. CONCLUSIONS: Increased aortic stiffness and LV diastolic dysfunction are strong predictors of new onset of AF among patients with systolic CHF. PMID- 27277159 TI - Serum drug levels to diagnose non-adherence in acute decompensated heart failure. AB - BACKGROUND: The aim of this study was to analyze medication non-adherence by measuring serum drug levels (SDL) in patients presenting with acute decompensated heart failure (ADHF). METHODS: Included in the study were chronic heart failure patients presenting with signs of acute decompensation. Blood sampling for the measurement of SDL was performed shortly after presentation. SDL were measured using liquid chromatography coupled with mass spectrometry. The estimation of SDL was calculated from the recommended chronic cardiac medications with the exception of drugs administered as part of the acute treatment prior to blood sampling. The patients were labeled as non-adherent when any one of the evaluated medications was not found in the serum. RESULTS: Fifty patients with ADHF were prospectively enrolled. All of the evaluated drugs were detected in the sera of 28 (56%) patients. Non-adherence was diagnosed in the remaining 22 (44%) patients. None of the evaluated medications was detected in the sera of 5 (10%) patients. CONCLUSION: The estimation of SDL indicates that non-adherence to the recommended chronic therapy is a common problem among patients presenting with ADHF. This method should be an essential aspect of routine clinical evaluation in these patients. PMID- 27277157 TI - Effect of glucocorticoids on osteoclast function in a mouse model of bone necrosis. AB - Osteonecrosis, also termed aseptic necrosis, is the cellular death of bone components due to interruption of the blood supply. Glucocorticoid (GC) therapy is a common non-traumatic cause of osteonecrosis. However, the mechanism by which GCs induce osteonecrosis remains to be elucidated. The aim of the present study was to investigate the effects of GCs on osteoclast and osteoblast differentiation and function in a GC-induced osteonecrosis mouse model. BALB/c male mice (n=40; 4-weeks-old) were treated with dexamethasone and asparaginase for 8 weeks. The control group (n=20) was administered normal saline. The results demonstrated that the GC-treated group had a lower mean weight compared with the control group. Morphologically, 16/37 (43%) mice demonstrated significant osteonecrotic lesions in the GC-treated group. However, osteonecrotic lesions were not observed in the mice of the control group. Furthermore, immunohistochemistry demonstrated that the GC-treated group had a higher level of osteoprotegerin compared with the control group, without any change in the expression of receptor activator of nuclear factor-kappaB ligand. In addition, tartarate-resistant acid-phosphatase staining demonstrated significantly decreased osteoclasts in the areas of bone destruction in the GCs-treated group. Furthermore, the present study demonstrated that GCs increased expression levels of osterix and osteocalcin, and decreased expression of matrix metallopeptidase-9 to regulate the differentiation and function of osteoblasts and osteoclasts. The results of the present study suggested that GCs influence bone remolding resulting in decreased osteoclasts formation/differentiation. Therefore, regulating the differentiation and activity of the osteoclasts may be beneficial to the control and treatment of osteonecrosis. PMID- 27277160 TI - Overlap in drug-disease associations between clinical practice guidelines and drug structured product label indications. AB - BACKGROUND: Clinical practice guidelines (CPGs) recommend pharmacologic treatments for clinical conditions, and drug structured product labels (SPLs) summarize approved treatment indications. Both resources are intended to promote evidence-based medical practices and guide clinicians' prescribing decisions. However, it is unclear how well CPG recommendations about pharmacologic therapies match SPL indications for recommended drugs. In this study, we perform text mining of CPG summaries to examine drug-disease associations in CPG recommendations and in SPL treatment indications for 15 common chronic conditions. METHODS: We constructed an initial text corpus of guideline summaries from the National Guideline Clearinghouse (NGC) from a set of manually selected ICD-9 codes for each of the 15 conditions. We obtained 377 relevant guideline summaries and their Major Recommendations section, which excludes guidelines for pediatric patients, pregnant or breastfeeding women, or for medical diagnoses not meeting inclusion criteria. A vocabulary of drug terms was derived from five medical taxonomies. We used named entity recognition, in combination with dictionary-based and ontology-based methods, to identify drug term occurrences in the text corpus and construct drug-disease associations. The ATC (Anatomical Therapeutic Chemical Classification) was utilized to perform drug name and drug class matching to construct the drug-disease associations from CPGs. We then obtained drug-disease associations from SPLs using conditions mentioned in their Indications section in SIDER. The primary outcomes were the frequency of drug disease associations in CPGs and SPLs, and the frequency of overlap between the two sets of drug-disease associations, with and without using taxonomic information from ATC. RESULTS: Without taxonomic information, we identified 1444 drug-disease associations across CPGs and SPLs for 15 common chronic conditions. Of these, 195 drug-disease associations overlapped between CPGs and SPLs, 917 associations occurred in CPGs only and 332 associations occurred in SPLs only. With taxonomic information, 859 unique drug-disease associations were identified, of which 152 of these drug-disease associations overlapped between CPGs and SPLs, 541 associations occurred in CPGs only, and 166 associations occurred in SPLs only. CONCLUSIONS: Our results suggest that CPG-recommended pharmacologic therapies and SPL indications do not overlap frequently when identifying drug disease associations using named entity recognition, although incorporating taxonomic relationships between drug names and drug classes into the approach improves the overlap. This has important implications in practice because conflicting or inconsistent evidence may complicate clinical decision making and implementation or measurement of best practices. PMID- 27277161 TI - IL-17A-producing T cells are associated with the progression of lung adenocarcinoma. AB - Accumulating evidence has shown that T cells are crucial in shaping the tumor microenvironment and regulating tumor development. However, the roles of IL-17A producing T cells (IL-17A+CD4+ Th17, IL-17A+CD8+ Tc17 and IL-17A+ gammadeltaT17 cells) and related cytokines in the progression of lung cancer (LC) remain uncertain. Here, we found that the frequencies of both Th17 and gammadeltaT17 cells in the peripheral blood of patients with lung adenocarcinoma (LA) were higher than those in healthy controls (HCs), whereas the frequency of Tc17 cells in the patients with LA was decreased. In addition, the frequencies of circulating Th17 and gammadeltaT17 cells, but not Tc17 cells, were positively associated with tumor invasion and metastasis. Furthermore, the major source of IL-17A production was Th17 cells, followed by Tc17 and gammadeltaT17 cells, in peripheral blood from patients with LA and HCs; but the percentages of Th17 and gammadeltaT17 cells in total intracellular IL-17A+ cells obtained from the patients with LC were higher than those from HCs. Moreover, the protein and corresponding mRNA levels of IL-17A, IL-23, IL-1beta, and TGF-beta1 were much higher in the patients with LA than those in HCs, and the levels of IL-17A in patients were positively correlated with numbers of both Th17 and gammadeltaT17 cells, but not Tc17 cells. Finally, the frequencies of circulating Th17 and gammadeltaT17 cells, along with the levels of IL-17A, IL-23, IL-1beta, and TGF beta1 were decreased in the patients with LA after tumor resection, whereas the frequency of circulating Tc17 cells was inversely increased in these patients. Our findings indicate that Th17, Tc17, gammadeltaT17 cells, and IL-17A-associated cytokines contribute to the development of LA and thus represent promising targets for therapeutic strategies. PMID- 27277163 TI - Thoracic laminectomy with spinal fixation in a nonambulatory patient with metastatic vertebral tumor from endometrial carcinoma. AB - Vertebral metastasis from endometrial cancer is a rare event and requires emergency treatment at the onset of neurologic symptoms caused by spinal cord compression. We report a case of a metastatic vertebral tumor, according to the International Federation of Gynecology and Obstetrics classification, of stage IVb endometrial cancer with multiple lung metastases. Emergency irradiation to the spinal tumor was conducted as a result of a loss of ambulation. Thoracic laminectomy with spinal fixation was subsequently performed because the patient remained nonambulatory and her neurological function deteriorated. Spinal decompression surgery enabled her to regain the ability to walk. Complete remission was achieved by subsequent pelvic surgery followed by combined chemotherapy consisting of docetaxel and carboplatin. Finally, the patient had no evidence of disease 45 months after the initial treatment. Early recognition and expeditious treatment is crucial for neurological recovery from metastatic spinal cord compression. PMID- 27277162 TI - Golgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis. AB - As the most abundant biopolymer on Earth, cellulose is a key structural component of the plant cell wall. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. While several proteins that affect CesA activity have been identified, components that regulate CSC assembly and trafficking remain unknown. Here we show that STELLO1 and 2 are Golgi-localized proteins that can interact with CesAs and control cellulose quantity. In the absence of STELLO function, the spatial distribution within the Golgi, secretion and activity of the CSCs are impaired indicating a central role of the STELLO proteins in CSC assembly. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen. Hence, we have uncovered proteins that regulate CSC assembly in the plant Golgi apparatus. PMID- 27277164 TI - Rhein lysinate decreases inflammation and adipose infiltration in KK/HlJ diabetic mice with non-alcoholic fatty liver disease. AB - The objective of this study was to investigate the protective effects of rhein lysinate (RHL) on the liver. Mice were divided into four groups: C57BL/J control, the KK/HlJ diabetic model, and 25 and 50 mg/kg/day RHL-treated KK/HlJ groups. The KK/HlJ diabetic mouse model was made by injecting STZ and feeding mice diabetic food. At 16 weeks, mice were sacrificed and their livers were harvested. The results indicated that compared with the C57BL/J control group, the body weights, liver weights and liver weight-to-body weight ratio were increased in KK/HlJ diabetic mice; however, these values were decreased following treatment with RHL. Compared with the C57BL/J control, KK/HlJ diabetic mice had a significantly lower level of SOD and GSH-px in their livers, but had a significantly higher level of MDA. However, these effects were ameliorated by RHL. Hepatic adipose infiltration was observed in KK/HlJ mice, but not in C57BL/J mice. RHL decreased the incidence of hepatic adipose infiltration and significantly decreased the expression of TNF alpha, IL-6, NF-kappaB, SREBP-1c, and Fas, as well as the phosphorylation of NF kappaB in the liver. In conclusion, RHL can improve hepatic function by decreasing hepatic adipose infiltration and the expression of inflammatory factors. PMID- 27277165 TI - Optimization of pancreatic lipase inhibitory and antioxidant activities of Ilex paraguariensis by using response surface methodology. AB - Response surface methodology (RSM) using a Box-Behnken design was used to optimize the extraction conditions for obtaining pancreatic lipase inhibitory and antioxidant principles from Ilex paraguariensis leaves. Three influencing factors: extraction time (min), the liquid-solid ratio, and ethanol concentration (%, v/v) were investigated in the ultrasonic extraction process. Optimization of the extraction conditions to obtain a product with minimum PL activity, maximum antioxidant activity, and maximum yield was performed using RSM by focusing on the three target influencing factors. The optimum conditions were established as the ethanol concentration (54.8 %), liquid-solid ratio (35.4), and extraction time (70.0 min). Under these conditions, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity, PL activity, extraction yield were 59.3 +/- 3.5, 35.3 +/- 3.0, and 34.4 +/- 0.4 %, respectively, similar to the theoretical predicted values of 59.7, 35.2, and 34.3 %, respectively. PMID- 27277166 TI - Current status of stress echocardiography: is it a required procedure for every sonographer? AB - BACKGROUND: Stress echocardiography is a versatile modality in the clinical cardiology. In its earlier days, its sole indication was restricted to diagnosing coronary artery disease. However, in response to the rapid development of ultrasound technology and analysis software, the indications have now evolved with expansion to several fields of cardiovascular disease. METHODS: I reviewed previous stress echocardiography publications, and discussed the current status of stress echocardiography in routine clinical setting. RESULTS: Although its portability and online assessment make possible for immediate diagnosis even at the bedside, establishment of an appropriate procedure and an accurate assessment require some experience. Other imaging competitors, such as multidetector computed tomography and cardiac magnetic resonance are gradually replacing the role of stress echocardiography in some fields. However, stress echocardiography has a potential for other new fields, including valvular heart disease and congestive heart failure. CONCLUSION: Although primary indication of stress echocardiography for coronary artery disease seems to be not relevant especially in Japan, novel indication of stress echocardiography in other field of cardiovascular disease is rapidly expanding in conjunction with the advent of new technology. Stress echocardiography is not a tool for limited researchers, but rather a fundamental routine method of choice for every sonographer. PMID- 27277167 TI - Role of cardiovascular echo in patients with Takayasu arteritis. AB - INTRODUCTION: Takayasu arteritis is an important differential diagnosis in young female patients presenting with fever, fatigue, hypertension, and/or neck pain. ECHOCARDIOGRAPHIC FEATURES: Aortic arch branch vessels are frequently affected and the carotid artery can have diffuse, homogeneous wall thickening, known as the 'macaroni sign'. The descending aorta can be stenotic with 'pseudo coarctation'. CONCLUSION: Cardiovascular echo plays an important role in the screening and characterization of arterial lesions in patients with Takayasu arteritis. PMID- 27277168 TI - Reverse atrial remodeling in patients who maintain sinus rhythm after electrical cardioversion: evidence derived from the measurement of total atrial conduction time assessed by PA-TDI interval. AB - BACKGROUND: A key mechanism of atrial fibrillation (AF) is atrial remodeling. Total atrial conduction time non-invasively assessed via tissue Doppler imaging (PA-TDI interval) may reflect the degree of electrical and structural atrial remodeling. The purpose of this study was to determine whether the PA-TDI interval is an independent predictor of recurrent AF after successful electrical cardioversion (eCV) and if it suggests reverse atrial remodeling. METHODS: Fifty one patients (mean +/- SD 66 +/- 10.6 years; 35 % women) with persistent AF and successful eCV were prospectively enrolled. The PA-TDI interval was measured 6 h and 90 days post-cardioversion. AF relapse was determined via 7-day Holter-ECG immediately after eCV and repeated after 90 days. RESULTS: Early recurrent AF (within 7 days) occurred in 21 patients (41.2 %), whereas after 90-day follow-up 26 patients (51 %) had AF recurrence. PA-TDI interval was longer in patients with AF recurrence within 90 days compared to patients who remained in sinus rhythm (SR) (149.1 +/- 8.3 vs. 129.8 +/- 10.9 ms, p < 0.0001). Optimal cut-off values for recurrent AF after 7 or 90 days from ROC analysis were 142 and 143 ms, respectively. Furthermore, the PA-TDI interval decreased significantly from baseline in those who remained in SR (129.8 +/- 10.9 vs. 125.8 +/- 10 ms, p < 0.0001), whereas the PA-TDI interval increased in patients who developed AF after 90 days (149.1 +/- 8.3 vs. 152 +/- 9 ms, p < 0.0001). CONCLUSIONS: The PA-TDI interval is an independent predictor of early and mid-term AF recurrence after eCV. Moreover, our data suggests reverse atrial remodeling in those patients who remained in stable SR. PMID- 27277169 TI - Right ventricular outflow tract systolic excursion: a useful method for determining right ventricular systolic function. AB - BACKGROUND: Assessment of right ventricular (RV) systolic function is not an easy task. Although RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) are useful in the assessment of RV function, their use can be sometimes limited. Right ventricular outflow tract systolic excursion (RVOT_SE) is a new way to evaluate RV systolic function. The aim of this study was to assess the correlation between RVOT_SE and other RV systolic function assessment methods. METHODS: RVOT_SE was defined as the systolic excursion of the RV outflow tract anterior wall endocardium. A total of 104 patients with a wide range of RV systolic function, ejection fraction, and pulmonary artery systolic pressure were studied. We also measured another four ways to evaluate RV systolic function, FAC, TAPSE, right ventricular outflow tract fractional shortening (RVOT_FS), and tricuspid annular systolic excursion velocity S' (Tissue S'). RESULTS: There was a strong correlation between RVOT_SE and each one of the four studied ways to evaluate RV systolic function. Multivariate regression analysis showed that the independent variables correlated with RVOT_SE were RVOT_FS (p < 0.0001), FAC (p = 0.005) and TAPSE (p = 0.023). RVOT_SE diagnosed patients with reduced RV systolic function with 98 % sensitivity and 96 % specificity. There was no correlation between RVOT_SE and ejection fraction, or between RVOT_SE and pulmonary artery systolic pressure in patients with reduced RV systolic function. Intra-observer and inter-observer reproducibility were favorable for RVOT_SE and all four studied ways. CONCLUSIONS: RVOT_SE is a simple, accurate, and promising method for evaluating RV systolic function. PMID- 27277170 TI - Visually confirmed post-systolic shortening during the recovery period in four cases of Takotsubo cardiomyopathy. AB - We report visually confirmed post-systolic shortening (PSS) during the recovery period and the relationship between PSS and electrocardiographic abnormalities in 4 cases of Takotsubo cardiomyopathy (TTC). In these 4 cases, the appearance of visually confirmed PSS during the recovery period coincided with observation of the deepest T wave and the longest QT interval. The transmural repolarization gradient and heterogeneous duration of myocardial contractions may cause PSS in the TTC recovery period. PMID- 27277171 TI - A case with discrete fibromuscular subaortic stenosis: evaluation by three dimensional echocardiography. PMID- 27277172 TI - Huge pericardial collaterals mistaken for newly developed pericardial effusion by transthoracic echocardiography in a liver transplant recipient. PMID- 27277173 TI - Pomolic acid inhibits metastasis of HER2 overexpressing breast cancer cells through inactivation of the ERK pathway. AB - Expression of the CXC chemokine receptor-4 (CXCR4), a G protein-coupled receptor, and HER2, a receptor tyrosine kinase, strongly correlates with tumor progression and metastatic potential of breast cancer cells. We report the identification of pomolic acid (PA) as a novel regulator of HER2 and CXCR4 expression. We found that PA downregulated the expression of HER2 and CXCR4 in SKBR3 cells in a dose- and time-dependent manner. When investigated for the molecular mechanism(s), it was found that the downregulation of HER2 and CXCR4 was not due to proteolytic degradation but rather to transcriptional regulation as indicated by downregulation of mRNA expression. Moreover, we show that PA inhibits phosphorylation of ERK and reduces NF-kappaB activation. Suppression of CXCR4 expression by PA correlated with the inhibition of CXCL12-induced invasion of HER2-overexpressing breast cancer cells. Overall, our results demonstrate for the first time that PA is a novel inhibitor of HER2 and CXCR4 expression via kinase pathways and may play a critical role in determining the metastatic potential of breast cancer cells. PMID- 27277174 TI - Evaluation of left ventricular rotation by two-dimensional speckle tracking method and real-time three-dimensional echocardiography: comparison with MRI tagging method. AB - BACKGROUND: Recently, it has become possible to evaluate left ventricular (LV) torsion by two-dimensional (2D) speckle tracking images. However, LV torsion is a three-dimensional (3D) performance, which per se cannot be assessed by the 2D speckle tracking method. The present study investigated the accuracy of the 2D speckle tracking method and real-time 3D echocardiography in measuring LV rotation, comparing with the MRI tagging method. METHODS: We assessed LV apical rotation using the 2D speckle tracking method, real-time 3D echocardiography, and MRI tagging method in 26 normal subjects, and compared the results of these three methods. LV apical rotation was measured just before the level in which the posterior papillary muscle was absorbed into the free wall. RESULTS: The degree of LV apical rotation evaluated by the 2D speckle tracking method (Deltatheta 2D) was significantly smaller than that evaluated by 3D echocardiography (Deltatheta 3D) and the MRI tagging method (Deltatheta MRI) (Deltatheta 2D 7.3 +/- 2.8 degrees ; Deltatheta 3D 8.8 +/- 3.4 degrees ; Deltatheta MRI 9.0 +/- 3.4 degrees ; Deltatheta 2D vs. Deltatheta 3D, p = 0.0001; Deltatheta 2D vs. Deltatheta MRI, p < 0.0001). There were good correlations among Deltatheta 2D, Deltatheta 3D, and Deltatheta MRI, but agreement between Deltatheta 3D and Deltatheta MRI (mean difference 0.14 +/- 1.43 degrees ) was better than that between Deltatheta 2D and Deltatheta MRI (mean difference 1.68 +/- 1.89 degrees ). CONCLUSION: The degree of LV apical rotation was underestimated with the 2D speckle tracking method compared with the MRI tagging method, whereas it could be precisely measured by 3D echocardiography. PMID- 27277175 TI - Detection of prolonged regional myocardial systolic dysfunction after exercise induced myocardial ischemia by strain echocardiography with high frame rate tissue Doppler echocardiography. AB - BACKGROUND: Strain echocardiography has enabled quantification of regional myocardial systolic function objectively and is less influenced by tethering effects and cardiac translational artifact than Doppler tissue imaging. Although strain echocardiography has been applied for the detection of inducible ischemia during dobutamine stress, it has not been fully applied to exercise stress echocardiography (ESE) because of technical difficulties. Prolonged myocardial systolic dysfunction after exercise-induced ischemia has been shown previously. Thus, we designed this study to evaluate whether the myocardial strain analysis can detect myocardial ischemia by the assessment of prolonged regional left ventricular (LV) dysfunction in ESE. METHODS: We performed ESE with myocardial strain imaging system in 20 consecutive patients who had exercise Tl-201 single photon emission computed tomography (SPECT). Myocardial strain curves were obtained at six segments in mid LV walls from the apical approach before and 5 min after ESE. We measured the duration from the R wave in the electrocardiogram to the timing of peak systolic strain corrected by the square root of the RR interval (TPSc). We finally calculated the differences of TPSc (DeltaTPSc) before ESE and 5 min after ESE. The results were compared with SPECT as a reference standard. RESULTS: A receiver operating characteristic curve demonstrated that a DeltaTPSc cutoff value of 70 ms had a sensitivity of 80% and a specificity of 84% for the detection of myocardial ischemia. CONCLUSIONS: Prolonged regional LV systolic dysfunction assessed by ESE with strain analysis was useful for the detection of myocardial ischemia. PMID- 27277176 TI - Aging change of left ventricular function in children evaluated by acoustic quantification method. AB - BACKGROUND: There are few reports about acoustic quantification (AQ) in the area of pediatrics. We aim to determine normal values of AQ analysis and investigate the aging change of left ventricular function in children. METHODS: The subjects in this study included 137 patients (aged 29 days to 18 years) who had normal cardiac function and no cardiac load. None of the patients were receiving medical therapy. The instrument used was a PH-6500 (Philips, Andevor). Change of left ventricular area in short-axis view was detected by AQ analysis. From the mitral inflow, peak early (E) and peak late (A) diastolic velocities were measured, and E/A was calculated. RESULTS: End-diastolic area (EDA) and end-systolic area (ESA) increased with age. Fractional area change (FAC) decreased with age. Peak ejection rate (PER) and peak rapid filling rate (PRFR) decreased with age up to 10 years. Atrial filling fraction (AFF) decreased and E/A increased with age up to 5 years. CONCLUSIONS: Maturational or developmental alterations in LV diastolic properties were found up to 5 years old. AQ analysis is one of the useful indexes for investigating left ventricular diastolic function. PMID- 27277177 TI - Determinants of plasma brain natriuretic peptide levels in untreated hypertensive patients. AB - BACKGROUND: Plasma brain natriuretic peptide (BNP) level is elevated in patients with left ventricular (LV) hypertrophy reflecting not only altered LV geometry but LV systolic and/or diastolic dysfunction. However, the values and limitations of BNP measurements are unclear in patients with untreated hypertension. In this study, plasma BNP level was compared with LV geometric and functional characteristics in patients with untreated hypertension. METHODS: Plasma BNP level was measured in 115 patients with untreated hypertension (72 males, 43 females, aged 60 +/- 12 years). Routine echo parameters of LV geometry and LV systolic and diastolic performance were also determined. RESULTS: LV ejection fraction was 67 +/- 6% and plasma BNP level was 32 +/- 30 pg/ml. Plasma BNP levels correlated with age, LV mass index (LVMI), and mitral E velocity, respectively (r = 0.46, p < 0.05; r = 0.21, p < 0.05; r = 0.29, p < 0.05, respectively), but not with systolic blood pressure or relative wall thickness (r = 0.01; r = -0.02). Plasma BNP level correlated with E/E' ratio (r = 0.27, p < 0.05, n = 77). When a stepwise multivariate analysis was performed, E velocity was selected in addition to age and LVMI as significant correlates of plasma BNP level. CONCLUSIONS: LVMI and E velocity were independent determinants of plasma BNP level in patients with untreated hypertension. Plasma BNP level is substantially useful for the screening of abnormalities of LV geometry and/or function in patients with untreated hypertension. Additional echocardiography is useful to assess the mechanism of the elevation of plasma BNP level in untreated hypertensive patients. PMID- 27277178 TI - Turbulent left-to-right shunt flow through the interatrial septum suggesting high left atrial pressure in patients with heart failure with preserved ejection fraction. AB - Lutembacher's syndrome is a combination of interatrial septal (IAS) defect or patent foramen ovale (PFO), associated with mitral stenosis. High left atrial (LA) pressure in mitral stenosis exaggerates left-to-right shunt in patients with interatrial communication. We present a case of heart failure with preserved ejection fraction. Echocardiography revealed normal left ventricular systolic function without mitral stenosis and turbulent left-to-right shunt through the IAS. The peak velocity of the shunt flow was 2.3 m/s and the estimated pressure gradient was 22 mmHg, indicating high LA pressure. The presence of turbulent left to-right shunt through the IAS is helpful for detecting high LA pressure. PMID- 27277179 TI - Type A aortic dissection with transient myocardial ischemia caused by intimal flap inverting into the left ventricle. AB - A 41-year-old man with sudden onset of chest oppression and downslope ST depression was diagnosed as having type A aortic dissection with angina pectoris and aortic regurgitation. Intraoperative transesophageal echocardiogram (TEE) showed intimal flap inverting into the left ventricle through the aortic valve. This case was rare in that transient myocardial ischemia was induced not by dissection of the aortic root reaching the coronary ostia but by back-and-forth movement of the intimal flap, covering the coronary ostia and interrupting the coronary artery flow. TEE was important for correct diagnosis. PMID- 27277180 TI - Giant asymptomatic left atrial myxoma. AB - The classic triad of myxoma clinical presentation is characterized by intracardiac obstruction, embolisms, and constitutional symptoms with fever, weight loss, or symptoms resembling connective tissue disease. Giant myxoma without symptoms are very rare. We present a case of a 30-year-old female with a giant asymptomatic myxoma in the left atrium, discovered by echocardiography. The patient was asymptomatic. PMID- 27277181 TI - Aspergillus cyst of aortic valve bioprosthesis. AB - Aspergillus endocarditis (AE) is an ominous complication of cardiac surgery with a dismal prognosis. We present a 35-year-old female who developed AE 4 months after her aortic and mitral valve replacement. Transesophageal echocardiography revealed an aortic root abscess and a cystic mass attached to the aortic bioprosthesis. Intraoperatively, the cyst was filled with fungal material. The aortic bioprosthesis was replaced and the patient was treated with amphotericin B. Six weeks later her condition suddenly deteriorated and she died on the same day. Early performance of transesophageal echocardiography and extended blood culture is mandatory in suspected cases of AE. PMID- 27277182 TI - Idiopathic internal jugular vein thrombosis in a patient with severe dizziness. AB - Upper torso deep vein thrombosis usually occurs in association with an indwelling venous catheter and/or malignancy as part of a paraneoplastic syndrome. However, idiopathic internal jugular vein thrombosis is a rare but potentially fatal condition. We report a 59-year-old woman who presented with severe dizziness. Ultrasonography and contrast-enhanced multislice computed tomography revealed thrombi in the left internal jugular vein. This patient had no malignancy, coagulation disorder, or infection. A ventilation/perfusion scan of the lungs showed no evidence of pulmonary embolism. This is a rare case of idiopathic thrombosis of the internal jugular vein. PMID- 27277183 TI - Suprasternal optical window to Doppler the superior vena cava in neonates. PMID- 27277184 TI - Severe dilated cardiomyopathy resulting in a globular cardiac silhouette on chest X-ray. PMID- 27277185 TI - Systolic anterior motion of the mitral valve induced by coughing. PMID- 27277186 TI - Visfatin attenuates the ox-LDL-induced senescence of endothelial progenitor cells by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway. AB - Endothelial progenitor cells (EPCs) play an important role in aging-associated senescence, thereby potentially contributing to vascular pathologies. Visfatin, identified as a new adipocytokine, is closely associated with the senescence of human cells. However, the effects of visfatin on the oxidized low-density lipoprotein (ox-LDL)-induced senescence of EPCs has not yet been explored, to the best of our knowledge. For this purpose, in the present study, we examined the effects of visfatin in ox-LDL-stimulated EPCs as well as the underlying mechanism responsible for these effects. We found that visfatin attenuated the ox-LDL induced senescence of EPCs by repressing beta-galactosidase expression and recovering telomerase activity. Western blot analysis confirmed that visfatin induced a dose-dependent increase in sirtuin 1 (SIRT1) expression in EPCs and ox LDL exposure decreased SIRT1 expression. Silencing SIRT1 abolished the inhibition of EPC senescence and the suppression of p53 expression induced by visfatin. Moreover, visfatin attenuated the inhibition of phosphorylation of Akt, phosphoinositide-3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) induced by ox-LDL. Taken together, these findings suggest that the treatment of EPCs with visfatin markedly attenuates the ox-LDL-induced senescence of EPCs by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway. PMID- 27277187 TI - High throughput sequencing of cyclic peptide immobilized on a gel-type single bead. AB - Relatively larger scale peptide libraries immobilized on a gel-type solid support consisting of 24 natural and non-natural amino acids by the "split and combine method" have been constructed to find interacting molecules. The diversity was ca. 200 millions of hexapeptides with cysteinyl residues forming cyclotide. Selected beads after screening can be sequenced by the conventional Edman degradation, although several restrictions and the problems are known. To resolve these, a novel combinatorial method involving partial acid hydrolysis followed by liquid chromatography with on-line mass spectrometric analyses has been established. Problems were uncovered in an early stage of the process. Uncertain assignment caused by byproducts derived from a cystine residue and other materials could be resolved by optimal hydrolysis conditions and derivatization before mass spectrometric analysis. Discrimination between Leu and Ile could be performed using high energy collision induced dissociation in the high resolution MALDI-TOF-MS/MS. The present optimized protocol is useful for discovery of sequences of interacting molecules and a second library construction. PMID- 27277188 TI - Isolation and characterization of autoantibodies against human cystatin C. AB - Hereditary cystatin C amyloid angiopathy (HCCAA) is a severe neurodegenerative disorder related to the point mutation in cystatin C gene resulting in human cystatin C (hCC) L68Q variant. One of the potential immunotherapeutic approaches to HCCAA treatment is based on naturally occurring antibodies against cystatin C. A recent growing interest in autoantibodies, especially in the context of neurodegenerative diseases, emerges from their potential use as valuable diagnostic markers and for controlling protein aggregation. In this work, we present characteristics of natural anti-hCC antibodies isolated from the IgG fraction of human serum by affinity chromatography. The electrophoresis (1-D and 2-D) results demonstrated that the isolated NAbs are a polyclonal mixture, but their electrophoretic properties did not allow to classify the new autoantibodies to any particular type of IgG. The Fc-glycan status of the studied autoantibodies was assessed using mass spectrometry analysis. For the isolated NAbs, the epitopic fragments in hCC sequence were identified by MS-assisted proteolytic excision of the immune complex and compared with the ones predicted theoretically. The knowledge of hCC fragments binding to NAbs and other ligands may contribute to the search for new diagnostic methods for amyloidosis of different types and the search for their treatment. PMID- 27277189 TI - Effect of esomeprazole, a proton pump inhibitor on the pharmacokinetics of sonidegib in healthy volunteers. AB - AIMS: This study aimed to evaluate the impact of esomeprazole on the pharmacokinetics of sonidegib. METHODS: This Phase I study evaluated the impact of the proton pump inhibitor (PPI) esomeprazole on the oral absorption and pharmacokinetics (PKs) of a single dose of sonidegib under fasted conditions. A total of 42 healthy subjects were enrolled to receive either sonidegib alone (200 mg single dose) or sonidegib in combination with esomeprazole (40 mg pre treatment 5 days and combination were given on day 6). Primary PK parameters assessed in the study were area under the concentration-time curve (AUC) from 0 14 days and 0-7 days and maximum observed plasma concentration (Cmax ). RESULTS: The plasma exposure (AUC0-14d, AUC0-7d and Cmax ) of a single 200 mg oral dose of sonidegib was decreased by 32-38% when sonidegib was co-administered with esomeprazole compared with sonidegib alone, with no apparent change in elimination slope and tmax . Baseline gastric pH was similar between the two arms. CONCLUSIONS: These results suggest a modest reduction in the extent of sonidegib absorption by esomeprazole. There was no obvious metabolic drug-drug interaction between the two agents. Both sonidegib and esomeprazole were well tolerated in the study population. PMID- 27277190 TI - In Vitro and In Vivo Differentiation of Progenitor Stem Cells Obtained After Mechanical Digestion of Human Dental Pulp. AB - Human population is facing a revolutionary change in the demographic structure with an increasing number of elderly people requiring an unmet need to ensure a smooth aging process and dental care is certainly an important aspect that has to be considered. To date, dentistry has been conservative and the need of transferring the scientific models of regenerative dentistry into clinical practice is becoming a necessity. The aim of this study was to characterize the differentiation commitment (in vitro) and the clinical grafting ability (in vivo) of a population of progenitor stem cells obtained after mechanical digestion of dental pulp with an innovative system recently developed. This approach was successfully used in previous studies to obtain a clinical-grade ready to use dental pulp fragments that could be grafted in autologous tissues to obtain bone. We are thus showing that micro grafts resulting from mechanical digestion contain stem cells with a mesenchymal phenotype, able to differentiate toward different cell types and to generate new bone in patients. We are providing data for the establishment of standardized and routinely oral surgery approaches, having outlined the cellular properties of human stem cells obtained from the dental pulp. This method can represent a valid tool for both regenerative medicine and tissue engineering purposes not only applicable to the cranio-maxillofacial region but, likely, to different bone pathologies for a fastening and healing recovering of patients. J. Cell. Physiol. 232: 548-555, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27277191 TI - Tibial component rotation during the unicompartmental knee arthroplasty: is the anterior superior iliac spine an appropriate landmark? AB - PURPOSE: No "ideal" landmark for tibial component rotation in medial unicompartmental knee arthroplasty (UKA) has been suggested by a biomechanical and clinical study. The aim of this study was to investigate whether the anterior superior iliac spine (ASIS) could provide a consistent rotational landmark of the tibial component during mobile-bearing medial UKA using computed tomography (CT). METHODS: During sagittal tibial resection, we utilized the ASIS as a rotational landmark. In 47 knees that underwent postoperative CT scans after medial UKA, the tibial component position was assessed by drawing a line tangential to the lateral wall of the tibial component. Rotation of the tibial component was measured using two reference lines: a line perpendicular to the posterior cortical rim of the tibia (angle alpha) and Akagi's line (angle beta). Instant bearing position and posterior cruciate ligament (PCL) fossa involvement were also evaluated. External rotation of the tibial component relative to each reference line was considered positive values. RESULTS: The mean alpha and beta angles were 8.0 degrees +/- 6.1 degrees (range -4.0 to 24.3) and 8.7 degrees +/- 4.8 degrees (range 1.9-25.2), respectively. Fourteen knees (29.8 %) showed PCL fossa involvement of the tibial resection margin. One bearing showed complete 180 degrees rotation at 2 weeks postoperatively. CONCLUSION: Due to the wide variation and inherent difficulty of identifying the ASIS during the operation, it is not recommended for guidance of sagittal tibial resection during medial UKA. In cases of inappropriate tibia component rotation, risk of PE bearing spinning and iatrogenic PCL injury should be reminded after medial UKA. LEVEL OF EVIDENCE: IV. PMID- 27277192 TI - Comparison of graft bending angle during knee motion after outside-in, trans portal and trans-tibial anterior cruciate ligament reconstruction. AB - PURPOSE: To determine graft bending angle (GBA) during knee motion after anatomic anterior cruciate ligament (ACL) reconstruction and to clarify whether surgical techniques affect GBA. Our hypotheses were that the graft bending angle would be highest at knee extension and the difference of surgical techniques would affect the bending steepness. METHODS: Eight healthy volunteers with a mean age of 29.3 +/- 3.0 years were recruited and 3D MRI knee models were created at three flexion angles (0 degrees , 90 degrees and 130 degrees ). Surgical simulation of the tunnel drilling was performed with anatomic tunnel position using each outside-in (OI), trans-portal (TP) and trans-tibial (TT) techniques on the identical cases. The models were matched to other knee positions and the GBA in 3D was measured using computational software. Double-bundle ACL reconstruction was analysed first, and single-bundle reconstruction was also analysed to evaluate its effect to reduce GBA. A repeated-measures ANOVA was used to compare GBA difference at three flexion angles, by three techniques or of three bundles. RESULTS: GBA changed substantially with knee motion, and it was highest at full extension (p < 0.001) in each surgical technique. OI technique exhibited highest GBA for anteromedial bundle (94.3 degrees +/- 5.2 degrees ) at extension, followed by TP (83.1 degrees +/- 6.5 degrees ) and TT (70.0 degrees +/- 5.2 degrees ) techniques (p < 0.01). GBA for posterolateral bundle at extension were also high in OI (84.6 degrees +/- 7.4 degrees ), TP (83.0 degrees +/- 6.3 degrees ) and TT (77.2 degrees +/- 7.0 degrees ) techniques (n.s.). Single-bundle grafts did not decrease GBA compared with double-bundle grafts. In OI technique, a more proximal location of the femoral exit reduced GBA of each bundle at extension and 90 degrees flexion. CONCLUSION: A significant GBA change with knee motion and considerably steep bending at full extension, especially with OI and TP techniques, were simulated. Although single-bundle technique did not reduce GBA as seen in double-bundle technique, proximal location of femoral exits by OI technique, with tunnels kept in anatomic position, was effective in decreasing GBA at knee extension and flexion. For clinical relevance, high stress on graft and bone interface has been suggested by steep GBA at full extension after anatomic ACL reconstruction. LEVEL OF EVIDENCE: Therapeutic study (prospective comparative study), Level II. PMID- 27277193 TI - Acute paraquat exposure determines dose-dependent oxidative injury of multiple organs and metabolic dysfunction in rats: impact on exercise tolerance. AB - This study investigated the pathological morphofunctional adaptations related to the imbalance of exercise tolerance triggered by paraquat (PQ) exposure in rats. The rats were randomized into four groups with eight animals each: (a) SAL (control): 0.5 ml of 0.9% NaCl solution; (b) PQ10: PQ 10 mg/kg; (c) PQ20: PQ 20 mg/kg; and (d) PQ30: PQ 30 mg/kg. Each group received a single injection of PQ. After 72 hours, the animals were subjected to an incremental aerobic running test until fatigue in order to determine exercise tolerance, blood glucose and lactate levels. After the next 24 h, lung, liver and skeletal muscle were collected for biometric, biochemical and morphological analyses. The animals exposed to PQ exhibited a significant anticipation of anaerobic metabolism during the incremental aerobic running test, a reduction in exercise tolerance and blood glucose levels as well as increased blood lactate levels during exercise compared to control animals. PQ exposure increased serum transaminase levels and reduced the glycogen contents in liver tissue and skeletal muscles. In the lung, the liver and the skeletal muscle, PQ exposure also increased the contents of malondialdehyde, protein carbonyl, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase and catalase, as well as a structural remodelling compared to the control group. All these changes were dose-dependent. Reduced exercise tolerance after PQ exposure was potentially influenced by pathological remodelling of multiple organs, in which glycogen depletion in the liver and skeletal muscle and the imbalance of glucose metabolism coexist with the induction of lipid, protein and DNA oxidation, a destructive process not counteracted by the upregulation of endogenous antioxidant enzymes. PMID- 27277194 TI - Acute posterior multifocal placoid pigment epitheliopathy in a patient with familial Mediterranean fever. PMID- 27277195 TI - Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis. AB - Serum levels of the lipid mediator sphingosine-1-phosphate (S1P) are reduced in septic patients and are inversely associated with disease severity. We show that serum S1P is reduced in human sepsis and in murine models of sepsis. We then investigated whether pharmacological or genetic approaches that alter serum S1P may attenuate cardiac dysfunction and whether S1P signaling might serve as a novel theragnostic tool in sepsis. Mice were challenged with lipopolysaccharide and peptidoglycan (LPS/PepG). LPS/PepG resulted in an impaired systolic contractility and reduced serum S1P. Administration of the immunomodulator FTY720 increased serum S1P, improved impaired systolic contractility and activated the phosphoinositide 3-kinase (PI3K)-pathway in the heart. Cardioprotective effects of FTY720 were abolished following administration of a S1P receptor 2 (S1P2) antagonist or a PI3K inhibitor. Sphingosine kinase-2 deficient mice had higher endogenous S1P levels and the LPS/PepG-induced impaired systolic contractility was attenuated in comparison with wild-type mice. Cardioprotective effects of FTY720 were confirmed in polymicrobial sepsis. We show here for the first time that the impaired left ventricular systolic contractility in experimental sepsis is attenuated by FTY720. Mechanistically, our results indicate that activation of S1P2 by increased serum S1P and the subsequent activation of the PI3K-Akt survival pathway significantly contributes to the observed cardioprotective effect of FTY720. PMID- 27277197 TI - miR-126-3p and miR-451a correlate with clinicopathological features of lung adenocarcinoma: The underlying molecular mechanisms. AB - Lung cancer is the most common malignancy worldwide. This study aimed to identify miRNA biomarkers of lung adenocarcinoma and to investigate their molecular mechanisms. miRNA expression profiling of tumor tissues and adjacent normal tissues from 10 patients were detected using microarray. Differentially expressed miRNAs (DEMs) were identified, and were verified using quantitative reverse transcription-PCR. Thereafter, correlations between DEM expression and clinicopathological features were determined in 49 patients. Furthermore, Targetscan was utilized to predict target genes, among which transcription factors (TFs) were identified. The interactions among miRNAs, TFs and target genes were used to construct an miRNA-TF-target network. Totally, 11 DEMs were identified, among which two downregulated miRNAs (miR-126-3p and miR-451a) were validated. Low levels of miR-126-3p and miR-451a were associated with poor pathological stage, large tumor diameter and lymph node metastasis (P<0.05). Receiver operating characteristic analysis showed that both miRNAs could predict pathological stage, tumor diameter and lymph node metastasis of lung adenocarcinoma (AUC >0.65, P<0.05). For miR-126-3p, 154 target genes were predicted (e.g., PLXNB2), which were enriched in 29 pathways mainly concerning apoptosis and cancer. For miR-451a, 397 target genes were predicted, which were enriched in 5 pathways including 'PPAR signaling pathway'. Ten genes were co regulated by miR-126-3p and miR-451a, e.g., TSC1. Furthermore, an miRNA-TF-target network was constructed, and a sub-network was identified, including 2 miRNAs, 15 targets, and 7 TFs. In conclusion, miR-126-3p and miR-451a predicted the severity of lung adenocarcinoma. However, the possible mechanisms explored by bioinformatics need to be further validated. PMID- 27277196 TI - MIC16 gene represents a potential novel genetic marker for population genetic studies of Toxoplasma gondii. AB - BACKGROUND: The zoonotic agent Toxoplasma gondii is distributed world-wide, and can infect a broad range of hosts including humans. Microneme protein 16 of T. gondii (TgMIC16) is responsible for binding to aldolase, and is associated with rhomboid cleavage and presence of trafficking signals during invasion. However, little is known of the TgMIC16 sequence diversity among T. gondii isolates from different hosts and geographical locations. RESULTS: In this study, we examined sequence variation in MIC16 gene among T. gondii isolates from different hosts and geographical regions. The entire genomic region of the MIC16 gene was amplified and sequenced, and phylogenetic relationship was reconstructed using Bayesian inference (BI) and maximum parsimony (MP) based on the MIC16 gene sequences. The results of sequence alignments showed two lengths of the sequence of MIC16 gene among all the examined 12 T. gondii strains: 4391 bp for strains TgCatBr5 and MAS, and 4394 bp for strains RH, TgPLH, GT1, PRU, QHO, PTG, PYS, GJS, CTG and TgToucan. Their A+T content ranged from 50.30 to 50.59 %. A total of 107 variable nucleotide positions (0.1-0.9 %) were identified, including 29 variations in 10 exons and 78 variations in 9 introns. Phylogenetic analysis of MIC16 sequences showed that typical genotypes (Type I, II and III) were able to be grouped into their respective genotypes. Moreover, the three major clonal lineages (Type I, II and III) can be differentiated by PCR-RFLP using restriction enzyme Pst I. CONCLUSIONS: Phylogenetic analysis and PCR-RFLP of the MIC16 locus among T. gondii isolates from different hosts and geographical regions allowed the differentiation of three major clonal lineages (Type I, II and III) into their respective genotypes, suggesting that MIC16 gene may provide a novel potential genetic marker for population genetic studies of T. gondii isolates. PMID- 27277199 TI - Implant integration: Problems at the interface. PMID- 27277200 TI - Platelets and coronary artery disease: Interactions with the blood vessel wall and cardiovascular devices. AB - In view of the rare presence of studies concerning platelet function as risk factor in atherosclerotic patients, processes underlying thromboembolic events are reviewed in this paper. The morphology and the structural organization membrane receptors, the open canalicular and dense tubular systems, the cytoskeleton, mitochondria, granules, lysosomes, and peroxisomes-of platelets are described. Platelet function under physiological conditions in atherosclerosis and after implantation of cardiovascular devices is summarized. PMID- 27277198 TI - The stepwise evolution of the exome during acquisition of docetaxel resistance in breast cancer cells. AB - BACKGROUND: Resistance to taxane-based therapy in breast cancer patients is a major clinical problem that may be addressed through insight of the genomic alterations leading to taxane resistance in breast cancer cells. In the current study we used whole exome sequencing to discover somatic genomic alterations, evolving across evolutionary stages during the acquisition of docetaxel resistance in breast cancer cell lines. RESULTS: Two human breast cancer in vitro models (MCF-7 and MDA-MB-231) of the step-wise acquisition of docetaxel resistance were developed by exposing cells to 18 gradually increasing concentrations of docetaxel. Whole exome sequencing performed at five successive stages during this process was used to identify single point mutational events, insertions/deletions and copy number alterations associated with the acquisition of docetaxel resistance. Acquired coding variation undergoing positive selection and harboring characteristics likely to be functional were further prioritized using network-based approaches. A number of genomic changes were found to be undergoing evolutionary selection, some of which were likely to be functional. Of the five stages of progression toward resistance, most resistance relevant genomic variation appeared to arise midway towards fully resistant cells corresponding to passage 31 (5 nM docetaxel) for MDA-MB-231 and passage 16 (1.2 nM docetaxel) for MCF-7, and where the cells also exhibited a period of reduced growth rate or arrest, respectively. MCF-7 cell acquired several copy number gains on chromosome 7, including ABC transporter genes, including ABCB1 and ABCB4, as well as DMTF1, CLDN12, CROT, and SRI. For MDA-MB-231 numerous copy number losses on chromosome X involving more than 30 genes was observed. Of these genes, CASK, POLA1, PRDX4, MED14 and PIGA were highly prioritized by the applied network-based gene ranking approach. At higher docetaxel concentration MCF-7 subclones exhibited a copy number loss in E2F4, and the gene encoding this important transcription factor was down-regulated in MCF-7 resistant cells. CONCLUSIONS: Our study of the evolution of acquired docetaxel resistance identified several genomic changes that might explain development of docetaxel resistance. Interestingly, the most relevant resistance-associated changes appeared to originate midway through the evolution towards fully resistant cell lines. Our data suggest that no single genomic event sufficiently predicts resistance to docetaxel, but require genomic alterations affecting multiple pathways that in concert establish the final resistance stage. PMID- 27277201 TI - The serial changes of perfusion index in preterm infants with patent ductus arteriosus: is perfusion index clinically significant? AB - BACKGROUND: Perfusion Index (PI) which reflects the peripheral blood flow may help early detection and treatment decision of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. The present study is designed to analyze the usefulness of PI level in early detection of hsPDA in preterm infants. METHODS: Preterm infants born before 36 gestational weeks were assessed for PI and simultaneous echocardiography. Based on echocardiography, each infant is categorized into no-PDA (group 1), non-hsPDA (group 2) and hsPDA (group 3). Heart rate (HR), mean arterial pressure (MAP), body temperature and oxygen saturation (SpO2) and concomitant PI were measured on days 1, 2, 3 and 4. RESULTS: In all preterm infants (N.=42) PI significantly increased from 0.7 on day 1 to 1.4 on day 4. The HR did not change by the days; however, the MAP increased on days 3 and 4 compared to day 1. In hsPDA group, the median PI was 0.7 (IQR, 0.4) on day 1 compared to 0.9 (IQR, 0.2) on day 2. PI is significantly lower in hsPDA group compared to no-PDA group on day 1 and 2; however, this difference disappeared at 48 hour on the intravenous ibuprofen treatment (on day 3 and 4). CONCLUSIONS: PI may predict the perfusion disorder and help to decide for treatment of hsPDA and was also helpful to monitor the response to treatment in hsPDA patients. PMID- 27277202 TI - Schistosoma haematobium infection, health and nutritional status in school-age children in a rural setting in Northern Senegal. AB - BACKGROUND: The aim of this study was to investigate the occurrence of urinary schistosomiasis in school children in a rural village of Northern Senegal, and to evaluate the impact of this parasitic infection on children's health, growth, and nutritional status. METHODS: A cross-sectional survey was carried out on 465 children resident in the village of Kassak Nord, in Senegal, in an area which is highly endemic for Schistosoma haematobium. Data on health, nutritional status and urinary schistosomiasis were collected. RESULTS: The overall prevalence of urinary schistosomiasis in school children in Kassak was 47.4%. As for malnutrition, 29.7% of children were malnourished (BMI-for-age Z-score [BAZ] <-2) and 14.5% had a significant linear growth retardation (height-for-age Z-score [HAZ] <-2). Children with urinary schistosomiasis showed lower mean BAZ and HAZ than uninfected children (HAZ positives -0.7+/-1.4 vs. HAZ negatives -0.4+/-1.4, P=0.004; BAZ positives -1.5+/-1 vs. BAZ negatives -1.3+/-1.1, P=0.03). It was also found that infected children were at greater risk of malnutrition (BAZ<-2; OR 1.5; 95% CI 1.01-2.26). CONCLUSIONS: The results of this study support the hypothesis that urinary schistosomiasis affects negatively childhood health and nutritional status and are of importance for planning intervention aimed to monitoring and control Urinary Schistosomiasis and malnutrition. PMID- 27277203 TI - Fecaloma, a hard nut to crack? PMID- 27277204 TI - Subacute osteomyelitis by Kingella kingae in a 5-year-old boy after chickenpox infection. PMID- 27277205 TI - Hypercalcemia and nephrocalcinosis complicating subcutaneous fat necrosis in a newborn after therapeutic hypothermia. PMID- 27277206 TI - Degradation of di(2-ethyl hexyl) phthalate by Fusarium culmorum: Kinetics, enzymatic activities and biodegradation pathway based on quantum chemical modelingpathway based on quantum chemical modeling. AB - Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in the manufacture of plastics, and it is an environmental contaminant. The specific growth rate (MU), maximum biomass (Xmax), biodegradation constant of DEHP (k), half-life (t1/2) of DEHP biodegradation and removal efficiency of DEHP, esterase and laccase specific activities, and enzymatic yield parameters were evaluated for Fusarium culmorum grown on media containing glucose and different concentrations of DEHP (0, 500 and 1000mg/L). The greatest MU and the largest Xmax occurred in media supplemented with 1000mg of DEHP/L. F. culmorum degraded 95% of the highest amount of DEHP tested (1000mg/L) within 60h of growth. The k and t1/2 were 0.024h(-1) and 28h, respectively, for both DEHP concentrations. The removal efficiency of DEHP was 99.8% and 99.9% for 1000 and 500mg/L, respectively. Much higher specific esterase activity than specific laccase activity was observed in all media tested. The compounds of biodegradation of DEHP were identified by GC MS. A DEHP biodegradation pathway by F. culmorum was proposed on the basis of the intermolecular flow of electrons of the identified intermediate compounds using quantum chemical modeling. DEHP was fully metabolized by F. culmorum with butanediol as the final product. This fungus offers great potential in bioremediation of environments polluted with DEHP. PMID- 27277207 TI - Functional redundancy as a tool for bioassessment: A test using riparian vegetation. AB - There is an urgent need to track how natural systems are responding to global change in order to better guide management efforts. Traditionally, taxonomically based metrics have been used as indicators of ecosystem integrity and conservation status. However, functional approaches offer promising advantages that can improve bioassessment performance. In this study, we aim to test the applicability of functional redundancy (FR), a functional feature related to the stability, resistance and resilience of ecosystems, as a tool for bioassessment, looking at woody riparian communities in particular. We used linear mixed-effect models to investigate the response of FR and other traditional biomonitoring indices to natural (drought duration) and anthropogenic stress gradients (flow regulation and agriculture) in a Mediterranean basin. Such indices include species richness, a taxonomic index, and the Riparian Quality Index, which is an index of ecological status. Then, we explored the ability of FR and the other indices to discriminate between different intensities of human alteration. FR showed higher explanatory capacity in response to multiple stressors, although we found significant negative relationships between all the biological indices (taxonomic, functional and ecological quality) and stress gradients. In addition, FR was the most accurate index to discriminate among different categories of human alteration in both perennial and intermittent river reaches, which allowed us to set threshold values to identify undisturbed (reference condition), moderately disturbed and highly disturbed reaches in the two types of river. Using these thresholds and the best-fitting model, we generated a map of human impact on the functional redundancy of riparian communities for all the stretches of the river network. Our results demonstrate that FR presents clear advantages over traditional methods, which suggests that it should be part of the biomonitoring toolbox used for environmental management so as to obtain better predictions of ecosystem response to environmental changes. PMID- 27277208 TI - Spatial response surface modelling in the presence of data paucity for the evaluation of potential human health risk due to the contamination of potable water resources. AB - Potential human health risk from waterborne diseases arising from unsatisfactory performance of on-site wastewater treatment systems is driven by landscape factors such as topography, soil characteristics, depth to water table, drainage characteristics and the presence of surface water bodies. These factors are present as random variables which are spatially distributed across a region. A methodological framework is presented that can be applied to model and evaluate the influence of various factors on waterborne disease potential. This framework is informed by spatial data and expert knowledge. For prediction at unsampled sites, interpolation methods were used to derive a spatially smoothed surface of disease potential which takes into account the uncertainty due to spatial variation at any pre-determined level of significance. This surface was constructed by accounting for the influence of multiple variables which appear to contribute to disease potential. The framework developed in this work strengthens the understanding of the characteristics of disease potential and provides predictions of this potential across a region. The study outcomes presented constitutes an innovative approach to environmental monitoring and management in the face of data paucity. PMID- 27277209 TI - Arsenic and arsenic species in shellfish and finfish from the western Arabian Gulf and consumer health risk assessment. AB - This study reports the levels of total arsenic and arsenic species in marine biota such as clams (Meretrix meretrix; N=21) and pearl oyster (Pinctada radiata; N=5) collected from nine costal sites in Jan 2014, and cuttlefish (Sepia pharaonis; N=8), shrimp (Penaeus semisulcatus; N=1), and seven commercially important finfish species (N=23) collected during Apr-May 2013 from seven offshore sites in the western Arabian Gulf. Total As and As species such as dimethylarsinic acid (DMA), arsenobetaine (AB), trimethylarsine oxide (TMAO), arsenocholine (AC), tetramethylarsonium ion (Tetra), arsenosugar-glycerol (As Gly) and inorganic As (iAs) were determined by using ICPMS and HPLC/ICPMS. In bivalves, the total As concentrations ranged from 16 to 118mg/kg dry mass; the toxic iAs fraction contributed on average less than 0.8% of the total As, while the nontoxic AB fraction formed around 58%. Total As concentrations for the remaining seafood (cuttlefish, shrimp and finfish) ranged from 11 to 134mg/kg dry mass and the iAs and AB fractions contributed on average 0.03% and 81% respectively of the total As. There was no significant relationship between the tissue concentrations of total As and iAs in the samples. There was also no significant relationship between As levels in seafood and geographical location or salinity of the waters from which samples were collected. Based on our results, we recommend introducing a maximum permissible level of arsenic in seafood from the Gulf based on iAs content rather than based on total As. Our analyses of cancer risks and non-cancer hazards identified non-negligible risks and the potential for hazards; the greatest risks were identified for expatriate consumers of bivalves and high-end consumers of seafood. Despite this, many uncertainties remain that would be best addressed by further analyses. PMID- 27277210 TI - Assessing the relationship between groundwater nitrate and animal feeding operations in Iowa (USA). AB - Nitrate-nitrogen is a common contaminant of drinking water in many agricultural areas of the United States of America (USA). Ingested nitrate from contaminated drinking water has been linked to an increased risk of several cancers, specific birth defects, and other diseases. In this research, we assessed the relationship between animal feeding operations (AFOs) and groundwater nitrate in private wells in Iowa. We characterized AFOs by swine and total animal units and type (open, confined, or mixed), and we evaluated the number and spatial intensities of AFOs in proximity to private wells. The types of AFO indicate the extent to which a facility is enclosed by a roof. Using linear regression models, we found significant positive associations between the total number of AFOs within 2km of a well (p trend <0.001), number of open AFOs within 5km of a well (p trend <0.001), and number of mixed AFOs within 30km of a well (p trend <0.001) and the log nitrate concentration. Additionally, we found significant increases in log nitrate in the top quartiles for AFO spatial intensity, open AFO spatial intensity, and mixed AFO spatial intensity compared to the bottom quartile (0.171log(mg/L), 0.319log(mg/L), and 0.541log(mg/L), respectively; all p<0.001). We also explored the spatial distribution of nitrate-nitrogen in drinking wells and found significant spatial clustering of high-nitrate wells (>5mg/L) compared with low-nitrate (<=5mg/L) wells (p=0.001). A generalized additive model for high nitrate status identified statistically significant areas of risk for high levels of nitrate. Adjustment for some AFO predictor variables explained a portion of the elevated nitrate risk. These results support a relationship between animal feeding operations and groundwater nitrate concentrations and differences in nitrate loss from confined AFOs vs. open or mixed types. PMID- 27277211 TI - Effect of high or low protamine dosing on postoperative bleeding following heparin anticoagulation in cardiac surgery. A randomised clinical trial. AB - While experimental data state that protamine exerts intrinsic anticoagulation effects, protamine is still frequently overdosed for heparin neutralisation during cardiac surgery with cardiopulmonary bypass (CPB). Since comparative studies are lacking, we assessed the influence of two protamine-to-heparin dosing ratios on perioperative haemostasis and bleeding, and hypothesised that protamine overdosing impairs the coagulation status following cardiac surgery. In this open label, multicentre, single-blinded, randomised controlled trial, patients undergoing on-pump coronary artery bypass graft surgery were assigned to a low (0.8; n=49) or high (1.3; n=47) protamine-to-heparin dosing group. The primary outcome was 24-hour blood loss. Patient haemostasis was monitored using rotational thromboelastometry and a thrombin generation assay. The low protamine to-heparin dosing ratio group received less protamine (329 +/- 95 vs 539 +/- 117 mg; p<0.001), while post-protamine activated clotting times were similar among groups. The high dosing group revealed increased intrinsic clotting times (236 +/ 74 vs 196 +/- 64 s; p=0.006) and the maximum post-protamine thrombin generation was less suppressed in the low dosing group (38 +/- 40 % vs 6 +/- 9 %; p=0.001). Postoperative blood loss was increased in the high dosing ratio group (615 ml; 95 % CI 500-830 ml vs 470 ml; 95 % CI 420-530 ml; p=0.021) when compared to the low dosing group, respectively. More patients in the high dosing group received fresh frozen plasma (11 % vs 0 %; p=0.02) and platelet concentrate (21 % vs 6 %; p=0.04) compared to the low dosing group. Our study confirms in vitro data that abundant protamine dosing is associated with increased postoperative blood loss and higher transfusion rates in cardiac surgery. PMID- 27277212 TI - The effect of Riluzole on functional recovery of locomotion in the rat sciatic nerve crush model. AB - PURPOSE: Peripheral nerve injury (PNI) is common disorder that represents more than 3 % of all traumatic injury cases. One type of PNI, sciatic nerve injury, leads to considerable motoneuron dysfunction. Because Riluzole is clinically approved for the treatment of motoneuron disease, we evaluated whether Riluzole treatment could enhance the nerve regeneration process and improve functional outcome after sciatic nerve crush in rats. METHODS: In acute treatment groups, a single dose of Riluzole (6 and 8 mg/kg) was administered intra-peritoneally 15 min after the crush nerve injury. In the chronic treatment groups, animals were treated with Riluzole (4 and 6 mg/kg/d) for 8 days. Sciatic functional index (SFI) was evaluated for 9 weeks after injury. Furthermore, electrophysiological and morphometric evaluations were performed at the 9th week following injury. RESULTS: Acute and chronic administrations of Riluzole immediately after sciatic nerve crush result in significantly delayed regeneration and reduced motor function outcome. CONCLUSIONS: These findings suggest that early administration of even a single dose of Riluzole after sciatic nerve crush injury can delay motor function recovery. This effect may not depend on its anti-nociceptive activity. PMID- 27277213 TI - Longitudinal assessment of health related quality of life of HIV infected patients treated for tuberculosis and HIV in a high burden setting. AB - INTRODUCTION: Assessment of patients receiving treatment for human immunodeficiency virus (HIV) and tuberculosis (TB) using a Health Related Quality of Life (HRQoL) instrument is important to get the subjective view of the patients' wellbeing. METHODS: We used the Functional Assessment of HIV Infection (FAHI) HRQoL instrument to collect perceived wellness information at baseline, month 3, 6 and 12 from patients enrolled in a pharmacokinetic study between March 2007 and April 2008. Composite domain scores at each time point and their relationship with the rate of adverse events (AEs) and serious adverse events were compared between treatment arms. RESULTS: Out of the 82 patients enrolled, 76 were analysed. There was a significant increase in total score in all groups between baseline, month 3, 6 and 12 (all p values < 0.0001), and over time (p < 0.001). Adjusting for baseline total score, baseline CD4 count had a significant effect on the total score over time (p = 0.002) and the rate of change in total score over time, that is; interaction effect (p < 0.001). There was no difference in each domain scores between participants that received ART with TB treatment and those that received TB treatment only. Respiratory AEs had a significant effect on HRQoL. CONCLUSION: We found that assessment of HRQoL of participants in TB-HIV treatment using the FAHI instrument was useful in evaluating treatment responses. It showed improvement consistent with decrease in adverse events and signs and symptoms of TB. Number and type of AEs was related to lower HRQoL in spite of TB cure. PMID- 27277215 TI - What constitutes an Arabian Helicobacter pylori? Lessons from comparative genomics. AB - BACKGROUND: Helicobacter pylori, the human gastric pathogen, causes a variety of gastric diseases ranging from mild gastritis to gastric cancer. While the studies on H. pylori are dominated by those based on either East Asian or Western strains, information regarding H. pylori strains prevalent in the Middle East remains scarce. Therefore, we carried out whole-genome sequencing and comparative analysis of three H. pylori strains isolated from three native Arab, Kuwaiti patients. MATERIALS AND METHODS: H. pylori strains were sequenced using Illumina platform. The sequence reads were filtered and draft genomes were assembled and annotated. Various pathogenicity-associated regions and phages present within the genomes were identified. Phylogenetic analysis was carried out to determine the genetic relatedness of Kuwaiti strains to various lineages of H. pylori. The core genome content and virulence-related genes were analyzed to assess the pathogenic potential. RESULTS: The three genomes clustered along with HpEurope strains in the phylogenetic tree comprising various H. pylori lineages. A total of 1187 genes spread among various functional classes were identified in the core genome analysis. The three genomes possessed a complete cagPAI and also retained most of the known outer membrane proteins as well as virulence-related genes. The cagA gene in all three strains consisted of an AB-C type EPIYA motif. CONCLUSIONS: The comparative genomic analysis of Kuwaiti H. pylori strains revealed a European ancestry and a high pathogenic potential. PMID- 27277214 TI - Development of monoclonal antibodies and serological assays including indirect ELISA and fluorescent microsphere immunoassays for diagnosis of porcine deltacoronavirus. AB - BACKGROUND: A novel porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was reported in China in 2012 and identified in the U.S. in early 2014. Since then, PDCoV has been identified in a number of U.S. states and linked with clinical disease including acute diarrhea and vomiting in the absence of other identifiable pathogens. Since PDCoV was just recently linked with clinical disease, few specific antibody-based reagents were available to assist in diagnosis of PDCoV and limited serological capabilities were available to detect an antibody response to this virus. Therefore, the overall objective of this project was to develop and validate selected diagnostic reagents and assays for PDCoV antigen and antibody detection. RESULTS: The nucleoprotein of PDCoV was expressed as a recombinant protein and purified for use as an antigen to immunize mice for polyclonal, hyperimmune sera and monoclonal antibody (mAb) production. The resulting mAbs were evaluated for use in fluorescent antibody staining methods to detect PDCoV infected cells following virus isolation attempts and for immunohistochemistry staining of intestinal tissues of infected pigs. The same antigen was used to develop serological tests to detect the antibody response to PDCoV in pigs following infection. Serum samples from swine herds with recent documentation of PDCoV infection and samples from expected naive herds were used for initial assay optimization. The tests were optimized in a checkerboard fashion to reduce signal to noise ratios using samples of known status. Statistical analysis was performed to establish assay cutoff values and assess diagnostic sensitivities and specificities. At least 629 known negative serum samples and 311 known positive samples were evaluated for each assay. The enzyme linked immunosorbent assay (ELISA) showed diagnostic sensitivity (DSe) of 96.1% and diagnostic specificity (DSp) of 96.2%. The fluorescent microsphere immunoassay (FMIA) showed a DSe of 95.8% and DSp of 98.1%. Both ELISA and FMIA detected seroconversion of challenged pigs between 8-14 days post-infection (DPI). An indirect fluorescent antibody (IFA) test was also developed using cell culture adapted PDCoV for comparative purposes. CONCLUSION: These new, specific reagents and serological assays will allow for improved diagnosis of PDCoV. Since many aspects of PDCoV infection and transmission are still not fully understood, the reagents and assays developed in this project should provide valuable tools to help understand this disease and to aid in the control and surveillance of porcine deltacoronavirus outbreaks. PMID- 27277216 TI - Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015. AB - We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease. PMID- 27277217 TI - Behavioural problems in the first year after Severe traumatic brain injury: a prospective multicentre study. AB - OBJECTIVE: To investigate the occurrence of behavioural problems in patients with severe traumatic brain injury during the first year after injury and potential associations with outcome. An additional post hoc objective was to analyse the frequency of behaviours with need for intervention from staff. DESIGN AND SETTING: In a prospective population based cohort study 114 patients with severe traumatic brain injury were assessed at three weeks, three months and one year after injury. MAIN MEASURES: Assessments included clinical examination and standardised instruments. Agitation was assessed with the Agitated Behaviour Scale, the course of recovery by the Rancho Los Amigo Scale and outcome by Glasgow Outcome Scale Extended. RESULTS: Agitation were most common at 3 weeks post injury and 28% ( n=68) of the patients showed at least one agitated behaviour requiring intervention from staff. Presence of significant agitation at 3 weeks after injury was not associated with poor outcome. At 3 months agitation was present in 11% ( n=90) and apathy in 26 out of 81 assessed patients. At 3 months agitation and apathy were associated with poor outcome at one year. CONCLUSIONS: Most agitated behaviours in the early phase are transient and are not associated with poor outcome. Agitation and apathy are uncommon at three months but when present are associated with poor outcome at one year after injury. In the early phase after a severe traumatic brain injury agitated behaviour in need of interventions from staff occur in a substantial proportion of patients. PMID- 27277218 TI - Differentiation of severe bilateral panuveitis following phacoemulsification: a case report. AB - BACKGROUND: Cataract surgery typically offers instant visual rehabilitation with rare postoperative complications. However, if complications occur, these complications may be confusing and threatening. We present a case of severe bilateral panuveitis following phacoemulsification and intraocular lens implantation and discuss the importance of a correct diagnosis and management. CASE PRESENTATION: A 75-year-old Asian male with bilateral phacoemulsification and intraocular lens implantation developed severe inflammation with sharp vision loss in both eyes after the surgeries. Physical examination indicated bilateral panuveitis. With a presumptive diagnosis of suppurative endophthalmitis and a history of effective treatment with intravenous antibiotics plus ofloxacin and steroid drops, intravenous ceftazidime and vancomycin were administered. However, the effects were minimal. With a supplemental history of recurrent oral, perineal, and gastrointestinal ulcers, a diagnosis of Behcet's disease was made, and systemic immune inhibitors were prescribed instead of invasive treatments, which might exacerbate the condition. After 5 days of medication, the inflammation was markedly relieved, and no recurrence was observed 2 weeks later. CONCLUSION: Correct differentiation of confusing conditions is crucial to implement appropriate management. Postoperative complications of cataract surgery should be differentiated carefully, and perioperative management in patients with autoimmune uveitis should be provided with caution. PMID- 27277219 TI - [Epidemiology of chronic venous diseases]. AB - AIM: Overview of the recent knowledge in epidemiology of chronic venous diseases. METHODS: Systematic search and discussion of recent studies concerning epidemiology of chronic venous diseases. RESULTS: The more recent epidemiologic studies of venous diseases in which the CEAP classification was used showed a prevalence of 60-70 % CEAP clinical class C0 and C1, app. 25 % for C2 and C3 and up to 5 % for C4 to C6 with skin changes or venous ulcers. The incidence of varicose veins is app. 2 % per year. CONCLUSIONS: Chronic venous diseases like varicose veins and chronic venous insufficiency belong to the most frequent diseases in our adult population. PMID- 27277221 TI - Effect of the presence of trophectoderm vesicles on blastocyst in relation to in vitro hatching, clinical pregnancy, and miscarriage rates. AB - Trophectoderm vesicles (TVs) are observed in some blastocysts that penetrate cells from the zona pellucida to the outer margin. Therefore, we compared this incidence in relation to hatching, pregnancy, and miscarriage rates between conventional in vitro fertilization (c-IVF) and intracytoplasmic sperm injection (ICSI). Vitrified/warmed blastocysts (n = 112) were derived from surplus embryos. The blastocysts were then observed using time-lapse cinematography to resolve the relationship between hatching and implantation. Another study was conducted that comprised 681 embryo transfer cycles in 533 patients who received a single vitrified/warmed blastocyst from our clinic. The incidence of TV was significantly higher in embryos inseminated by ICSI compared with c-IVF [ICSI: 51/56 (91 %); c-IVF: 25/56 (45 %); P < 0.01]. The successful hatching rate was significantly lower in ICSI than in c-IVF [ICSI: 11/56 (20 %); c-IVF: 29/56 (52 %); P < 0.01]. In addition, the hatching rate was significantly lower when TVs were present (14/76; 18 %) than in non-TV embryos (26/36; 72 %) (P < 0.01). In regard to the clinical study results, no significant differences were found between the groups in the pregnancy rate (TV present group: 107/183, 58.5 %; TV absent group: 273/498, 54.8 %) and miscarriage rate (TV present group: 21/107, 19.6 %; TV absent group: 53/273, 19.4 %). In vivo, we hypothesized that hatching and hatched would occur naturally by assisting protease action in the uterus; therefore, these results suggest that the presence of TV has no effect on pregnancy rates in the clinical setting. PMID- 27277222 TI - Ultrasound in the field of urology. PMID- 27277220 TI - International Paediatric Mitochondrial Disease Scale. AB - OBJECTIVE: There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study. METHODS: A clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6-16 years) from five different expert centres from four different continents were evaluated in this study. RESULTS: The feasibility of the IPMDS was good, as indicated by a low number of missing items (4 %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9 % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23-0.99). CONCLUSION: In conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials. PMID- 27277223 TI - Morphological and functional evaluation of normal and abnormal fetal growth by ultrasonography. AB - Correction or estimation of gestational age is essential for the evaluation of fetal growth. When necessary, an appropriate fetal biometric parameter should be selected depending on fetal size. In the first trimester, crown-rump length (CRL) is appropriate, especially when the CRL is 20-40 mm. In the second trimester, biparietal diameter (BPD), head circumference (HC), and femur length (FL) are of equal predictability. Fetal weight estimation is still the basis of evaluation of fetal growth. The most predictable formula currently available includes the parameters BPD (or HC), abdominal circumference (AC), and FL. Serial measurements of AC are useful for diagnosis of intrauterine growth restriction (IUGR) and macrosomia. Quantitative evaluation of soft tissue deposition may be informative for macrosomia. Functional evaluation using Doppler velocimetry is essential in IUGR cases associated with uteroplacental insufficiency. Analysis of blood velocity waveforms of the umbilical and intracranial arteries, predominantly the middle cerebral artery, is widely performed. An increase in the pulsatility index (PI) or resistance index (RI) of the umbilical artery and/or a decrease in the PI or RI of the middle cerebral artery are highly predictable for fetal hypoxia and/or acidosis. PMID- 27277224 TI - Participation of mast cells in angiogenesis in the border zone of myocardial infarction in rats. AB - BACKGROUND: We hypothesized that mast cells may participate in coronary angiogenesis in acute myocardial infarction, contributing to myocardial salvage. METHODS: The left coronary artery was occluded in control (n = 30) and Ws rats (n = 30), which genetically lacked c-kit, resulting in a mast cell deficiency. Four weeks later, the infarct area, i.e., infarct core and surrounding infarct areas, and the non-infarct area were assessed histopathologically. The mast cell and small vessel densities were assessed using toluidine blue and alkaline phosphatase staining. Myocardial perfusion was assessed by myocardial contrast echocardiography (MCE). RESULTS: In Ws rats, the percentage infarct core area increased (p < 0.05) compared with the controls, whereas the percentage surrounding infarct area decreased (p < 0.01). Mast cell density increased most in the surrounding infarct area (p < 0.01) in control rats, whereas mast cells were absent in Ws rats. Compared with the controls, coronary microvessel density decreased in the surrounding infarct area in Ws rats (p < 0.01). MCE showed that the percentage infarct core area, i.e., perfusion defect, increased (p < 0.05) and the percentage surrounding infarct area, i.e., reduced perfusion area, decreased (p < 0.01) in Ws rats. CONCLUSION: Mast cells may participate in promoting coronary angiogenesis in the infarct area surrounding the infarct core, contributing to attenuation of left ventricular dysfunction. PMID- 27277225 TI - Relationship between upper limb peripheral artery stiffness using the radial artery and atherosclerotic parameters. AB - PURPOSE: A new method has been developed for evaluating arterial stiffness using transcutaneous and high-frequency ultrasound. There may be a difference in the clinical significance of peripheral arteries, such as the radial artery (a muscular property), and other medium/large-sized arteries (an elastic property). The aim of this study was to determine the relationship between upper limb peripheral arterial stiffness (ULPAS) using the new method for the radial artery and atherosclerotic parameters in comparison with carotid intima-media thickness (IMT) and cardio-ankle vascular index (CAVI) in a healthy population and a diseased population with hypertension (HT) and diabetes mellitus (DM). METHODS: Forty-four apparently healthy individuals (mean age = 26.3 years, men/women = 14/30), 45 patients with drug-treated HT (mean age = 55.3 years, men/women = 17/28), and 37 patients with drug-treated DM (mean age = 55.2 years, men/women = 21/16) were investigated. Body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), CAVI, IMT, ultrasonographically measured ULPAS, blood lipid/glucose-related parameters, and C-reactive protein (CRP) were all determined. RESULTS: Among the healthy subjects, ULPAS showed a significantly positive correlation with SBP and CRP. ULPAS showed a different correlation pattern with atherosclerotic parameters from that of IMT and CAVI. The HT subjects had significantly higher ULPAS levels than those with DM. In this diseased population, ULPAS showed a significant positive correlation with SBP and DBP, as well as a significant negative correlation with glucose. CONCLUSION: These results suggest that ULPAS may provide new information in association with some atherosclerotic conditions as a unique index different from IMT and CAVI. PMID- 27277226 TI - Initial experience of transcranial contrast-enhanced ultrasonography with Sonazoid in the evaluation of microvascular brain anatomy. AB - PURPOSE: The aim of this study is to visualize the microvascular anatomy of the brain parenchyma using transcranial contrast-enhanced ultrasonography (TCEUS) with Sonazoid. METHODS: TCEUS was performed in 14 subjects using the transtemporal and transnuchal approach (two patients with cerebral infarction and 12 healthy volunteers). An ultrasound system equipped with a 2- to 4-MHz sector probe set to coded phase inversion mode with a mechanical index of 0.4 was used. An intravenous bolus of Sonazoid (0.01 ml/kg) was injected. First-pass perfusion images were recorded from injection to 50 s after injection, and flush replenishment (FR) images were recorded three times on both sides of the head from 1 to 5 min after injection. RESULTS: Real-time perfusion images of the brain parenchyma could be observed in all cases. At first pass, the main cerebral arteries began to be visualized at 10-20 s after injection, followed by the microvasculature at 15-30 s. The microvasculature reconstructed by the FR method could be observed on both sides of the head. CONCLUSION: TCEUS with Sonazoid allows effective, noninvasive evaluation of brain parenchyma microvasculature. PMID- 27277227 TI - Case of right-neck tumor that appears to be ectopic thymus. AB - A 7-year-old female infant presented with an asymptomatic soft tissue mass in the right neck. The tumor was considered to be a benign one because it had a smooth margin and no change in its size was observed. Ultrasonography showed a 4.5-cm diameter solid tumor with a smooth, well-defined border. Inside the tumor, flow signals were observed on color Doppler and there were numerous echogenic spots. Magnetic resonance imaging (MRI) examination showed findings consistent with an ectopic thymus, i.e., T1- and T2-weighted images showed thymus-like signals. The course of the case is being continuously followed. PMID- 27277228 TI - Evaluation of congenital left ventricular aneurysm in the fetus by velocity vector imaging. AB - We report a case of left ventricular aneurysm evaluated using the velocity vector imaging (VVI) technique, an angle-independent method used to calculate the tissue velocity strain and strain rate on routine gray scale two-dimensional images and display the velocities of endocardial points as vectors overlaid on B-mode images. It uses a combination of speckle tracking and complex geometric analysis, allowing tracing of myocardial activity throughout the cardiac cycle. In this case, evaluation of the myocardial dynamics in the fetus by VVI was started at 27 weeks of gestation, and both the systolic and diastolic velocities and the ejection fraction in the aneurysmal segment were less than in the other segments. VVI imaging at 35 weeks of gestation showed this difference even more clearly. Postnatal VVI examination showed no significant difference between results for the systolic and diastolic velocities or ejection fraction and those obtained at the prenatal VVI examination. VVI seemed to be as useful at this time, especially for assessing ventricular systolic function, as it was for postnatal examination. PMID- 27277229 TI - Asymptomatic emphysematous cholecystitis. AB - Emphysematous cholecystitis (EC) is a life-threatening complication of acute cholecystitis. Its clinical manifestations are usually vague, but asymptomatic cases are very rare. We present such a case with an emphasis on sonographic (US) findings. In this case, detection of gas echoes in the gallbladder wall and the surrounding hepatic tissue led us to an appropriate treatment. US is now the technique of first choice for diagnosing gallbladder diseases, and knowledge of US findings encountered in this case can help prevent a hazardous delay in emergent treatment. PMID- 27277230 TI - Accuracy of ultrasonographic fetal weight estimation in Japanese twin pregnancies. PMID- 27277231 TI - Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons. AB - BACKGROUND: Pathological Golgi fragmentation represents a constant pre-clinical feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) but its molecular mechanisms remain hitherto unclear. RESULTS: Here, we show that the severe Golgi fragmentation in transgenic mutant SOD1(G85R) and SOD1(G93A) mouse motor neurons is associated with defective polymerization of Golgi-derived microtubules, loss of the COPI coat subunit beta-COP, cytoplasmic dispersion of the Golgi tether GM130, strong accumulation of the ER-Golgi v SNAREs GS15 and GS28 as well as tubular/vesicular Golgi fragmentation. Data mining, transcriptomic and protein analyses demonstrate that both SOD1 mutants cause early presymptomatic and rapidly progressive up-regulation of the microtubule-destabilizing proteins Stathmins 1 and 2. Remarkably, mutant SOD1 triggered Golgi fragmentation and Golgi SNARE accumulation are recapitulated by Stathmin 1/2 overexpression but completely rescued by Stathmin 1/2 knockdown or the microtubule-stabilizing drug Taxol. CONCLUSIONS: We conclude that Stathmin triggered microtubule destabilization mediates Golgi fragmentation in mutant SOD1 linked ALS and potentially also in related motor neuron diseases. PMID- 27277232 TI - First ultrastructural data on the human tapeworm Taenia asiatica eggs by scanning and transmission electron microscopy (SEM, TEM). AB - Humans are definitive hosts of three species of the Taenia genus, namely Taenia solium, Taenia saginata and Taenia asiatica. The relative novelty of the latter explains the lack of knowledge concerning certain relevant aspects related to this parasite, such as its definite geographical distribution and whether its eggs can infect humans or not. So far, only the eggs of T. solium are known to be infective for humans, producing cysticercosis. Although eggs contain the infective stage, the oncosphere, there is a lack of research on the ultrastructure of eggs of human taeniids. We show, for the first time, the ultrastructure of eggs of T. asiatica by means of SEM and TEM analyses. We detected all the envelopes, namely the egg shell, vitelline layer, outer embryophoric membrane, embryophore, granular layer, basal membrane, oncospheral membrane and oncospheral tegument. Hooks surrounded by myofibrils and glycogen like particles, the two types of secretory granules of the penetration glands, as well as several nuclei and mitochondria were also revealed in the oncospheres. In addition to the already known structures in eggs from other Taenia species, the presence of two types of small vesicles is described herein, possibly corresponding to exosomes and ectosomes because of their shape and size, which could participate in the host/parasite intercellular communication. PMID- 27277233 TI - DNA extraction methods and multiple sampling to improve molecular diagnosis of Sarcocystis spp. in cattle hearts. AB - Molecular detection of Sarcocystis spp. in tissue samples can be useful for experimental and diagnostic purposes. However, the parasite spreads unevenly through tissues, forming tissue cysts, and the cystic wall is an obstacle in DNA extraction protocols. Therefore, adequate sampling and effective disruption of the cysts are essential to improve the accuracy of DNA detection by PCR. The aims of this study were to evaluate the suitability of four protocols for DNA extraction from cysts of Sarcocystis spp. present in bovine myocardium samples or after their harvest in phosphate-buffered saline (PBS) solution as well as determine the effects of single or multiple sampling on the accuracy of molecular diagnosis of sarcocystosis in cattle hearts. Cysts and myocardium samples from nine bovine hearts were randomly distributed to four DNA extraction protocols: kit, kit with modification, DNAzol, and cetyl-trimethyl ammonium bromide (CTAB). Samples were submitted to DNA extraction and PCR as replicates of each heart (simplicate, duplicate, and triplicate), and the probability of a true positive diagnostic was calculated. Among the protocols tested, the kit with modification was determined to be the most suitable for DNA extraction from cysts in PBS solution (92.6 % of DNA detection by PCR); DNAzol resulted in higher DNA detection frequency from bovine myocardium samples (48.1 %). Multiple sampling improved the molecular diagnosis of Sarcocystis spp. infection in cattle hearts, increasing at 22.2 % the rate of true positive diagnostic. PMID- 27277234 TI - Patient men win the day. PMID- 27277235 TI - Effects of a vertical console position on operator muscular stress during ultrasonic diagnosis. AB - Ultrasound examinations tend to put sonographers in unnatural postures, which may lead to musculoskeletal disorders. In this study, we focused on the height of the operation panel of the diagnostic ultrasound system to quantitatively assess the effects of panel height (work plane height) on musculoskeletal stress during scanning in a sitting position. Eight subjects were asked to perform a simulated scanning task that involved touching nine points on the operation panel at four different panel heights. Electromyogram, left wrist joint angle, and subjective evaluation on ease of manipulation, etc., indicated that the optimum height of the operation panel during scanning in a sitting position is elbow height. PMID- 27277236 TI - In vitro study of ultrasound radiation force-driven twinkling sign using PVA-H gel and glass beads tissue-mimicking phantom. AB - The twinkling sign observed in ultrasound coded-excitation imaging (e.g., GE B Flow) has been reported in previous research as a potential phenomenon to detect micro calcification in soft tissue. However, the mechanism of the twinkling sign has not been clearly understood yet. We conducted an in vitro experiment to clarify the mechanism of the twinkling sign by measuring a soft tissue-mimicking phantom with ultrasonic and optical devices. A soft tissue-mimicking phantom was made of poly(vinyl alcohol) hydro (PVA-H) gel and 200-MUm-diameter glass beads. We applied ultrasound to the phantom using medical ultrasound diagnostic equipment to observe the twinkling sign of glass beads. Optical imaging with a laser sheet and a high-speed camera was performed to capture the scatter lights of the glass beads with and without ultrasound radiation. The scatter lights from the glass beads were quantified and analyzed to evaluate their oscillations driven by the ultrasound radiation force. The twinkling sign from the glass beads embedded in the PVA-H gel soft tissue phantom was observed in ultrasound B-Flow color imaging. The intensity and oscillation of the scattered lights from the glass beads showed significant difference between the cases with and without ultrasound radiation. The results showed a close relationship between the occurrence of the twinkling sign and the variations of the scatter lights of glass beads, indicating that ultrasound radiation force-driven micro oscillation causes the twinkling sign of micro calcification in soft tissue. PMID- 27277237 TI - Cardiac variation of inferior vena cava: new concept in the evaluation of intravascular blood volume. AB - Evaluation of the intravascular blood volume is an important assessment in emergency and critical care medicine. Measurement of the inferior vena cava (IVC) respiratory variation by ultrasound echography is useful, but it entails subjective problems. We have hypothesized that IVC cardiac variation is also correlated with intravascular blood volume and analyzed it automatically using computer software of two kinds, later comparing the results. Snakes, software to track boundaries by curve line continuity, and template matching software were incorporated into a computer with an ultrasound machine to track the short-axis view of IVC automatically and analyze it with approximation by ellipse. Eight healthy volunteers with temporary mild hypovolemia underwent echography before and after passive leg raising and while wearing medical anti-shock trousers. IVC cardiac variation was visually decreased by both leg raising and medical anti shock trousers. The collapse index (maximum - minimum/maximum) of area during three cardiac beats was decreased showing a good relationship to fluid load simulations; 0.24 +/- 0.03 at baseline versus 0.11 +/- 0.01 with leg raising and 0.12 +/- 0.01 with medical anti-shock trousers. In conclusion, IVC cardiac variation has the potential to provide an evaluation of water volume. It presents some advantages in mechanical analysis over respiratory variation. At the very least, we need to exercise some caution with cardiac variation when evaluating respiratory variation. PMID- 27277238 TI - Diagnostic value of endoscopic ultrasound-guided directional eFLOW in solid pancreatic lesions. AB - AIM: Ultrasound using microbubble-based contrast agents is useful for vascular imaging. Directional eFLOW (D-eFLOW) is a novel technology for vascular assessment that provides high spatial and temporal resolution. The purpose of this study was to investigate the utility of endoscopic ultrasound (EUS)-guided D eFlow before and after administration of an ultrasound contrast agent (USCA) for assessing the vascularity of solid pancreatic lesions. MATERIALS AND METHODS: D eFlow was compared to power Doppler EUS (PD-EUS) or color Doppler EUS (CD-EUS) before and after USCA injection. We also evaluated the Visual Vascular Assessment (ViVA) scale for the estimation of vascularity and investigated its reliability using the interclass correlation coefficient (ICC). From January 2007 to March 2007, 35 patients (mean age, 64.5 years old; age range, 28-81 years) underwent EUS followed by D-eFLOW EUS, PD-EUS, and CD-EUS before and after administration of USCA. The pancreatic parenchymal ViVA score, pancreatic vascular pattern, and ICC were evaluated for all lesions. RESULTS: Concerning the sensitivity for detection of the hypovascular pattern in pancreatic adenocarcinoma, D-eFLOW (before and after USCA) had similar sensitivity to PD-EUS (before and after USCA) and CD-EUS (before and after USCA). D-eFLOW after contrast showed the highest accuracy (82.3 %) and negative predictive value (53.8 %) among all the modalities investigated. There was a good correlation among the ViVA scores for D-eFLOW before contrast, those for D-eFLOW EUS, and those for PD-EUS and CD-EUS. The reliability of the ViVA scale was excellent with an ICC of 0.81. In conclusion, D eFLOW EUS is a sensitive, reliable, and highly accurate method of assessment of pancreatic vascularity. D-eFLOW EUS with contrast was more sensitive than PD-EUS and CD-EUS for assessment of pancreatic vascularity. PMID- 27277239 TI - Ultrasonographic thyroid nodular findings in Japanese children. AB - PURPOSE: The Fukushima Health Management Survey conducted after the accident at the Fukushima Nuclear Power Plant included thyroid ultrasound examinations for children aged <=18 years at the time of the accident. The purpose of this study was to investigate the frequency of thyroid nodular lesions detected using high quality ultrasonography in a general population of Japanese children, in whom such data have not been previously characterized. METHODS: The current study investigated 4,365 free-living children aged between 3 and 18 years in three Japanese prefectures (Aomori, Yamanashi and Nagasaki). The same ultrasonography equipment as that used in the Fukushima Survey was employed to observe thyroid nodular lesions. The following categories of findings were used-'A', further examinations are not necessary; 'B', the presence of thyroid nodules with a diameter of >=5.1 mm or thyroid cysts with a diameter of >=20.1 mm; and 'C', immediate further examinations are required. As a sub-category of 'A', 'A1' was defined as the absence of nodules or cysts, and 'A2' was defined as the presence of thyroid nodules with a diameter of <=5.0 mm or thyroid cysts with a diameter of <=20.0 mm. RESULTS: Overall, 4,321 (99 %) of the total participants were classified with a status of 'A' and 44 (1 %) were classified with a status of 'B'. No participants were classified with a status of 'C'. A total of 56.5 % of the total participants was classified with a status of 'A2'. Thyroid nodules were identified in 1.6 % of the total participants and thyroid cysts were identified in 56.9 % of the participants. CONCLUSION: The current study provides data regarding the actual frequency of ultrasonographically detected thyroid nodular lesions among the Japanese children. These results would be useful for evaluating thyroid findings in Japanese children, although careful interpretation is required. PMID- 27277240 TI - Sonohysterosalpingography: a suitable choice in infertility workup. AB - PURPOSE: To evaluate the efficacy, compliance, and cost effectiveness of sonohysterosalpingography (HyCoSy) compared with hysteroscopy for uterine cavity evaluation and compared with RX-hysterosalpingography (RX-HSG) for tubal patency determination. METHODS: Three hundred and eight infertile patients underwent HyCoSy, hysteroscopy, and RX-HSG. We compared sensitivity, specificity, positive and negative predictive values (PPV and NPV), discomfort level, and cost of all three procedures. RESULTS: Sensitivity, specificity, PPV, and NPV were higher for HyCoSy than for hysteroscopy but the differences were not significant. HyCoSy also has the same accuracy as RX-HSG. Pain perception and cost were higher for RX HSG and hysteroscopy than for HyCoSy. CONCLUSIONS: HyCoSy can be regarded as a procedure for initial evaluation of the uterine cavity and of tubal patency in infertile patients. PMID- 27277241 TI - Value of ultrasonography for observation of early healing of humeral shaft fractures. AB - PURPOSE: Explore the value of ultrasonography for observation of early healing of humeral shaft fractures. METHODS: Sixty-five humeral shaft fracture patients were recruited. They were examined sonographically with color Doppler ultrasonography (CDU) and/or power Doppler ultrasonography (PDU) during the 1st week, 2nd week, 3rd week, 4th week, 9th week, and 15th week after the initial surgical procedure of internal fixation. Formation of callus consolidation and the resistance indexes (RI) of blood flow in different durations were compared between the good healing group and bad healing (delayed fracture healing or nonunion) group. RESULTS: Ultrasound showed that 59 patients had good fracture healing. Within the 2nd and 4th week after surgery, the RI decreased over time (P < 0.05) and color Doppler flow imaging (CDFI/PDU) grading ranged from II to III. Six patients had bad fracture healing (delayed healing or nonunion). Insufficient or absent blood flow signals demonstrated that no callus was found in and/or around the fracture sites. CDFI grading ranged from 0 to I. There was significant difference compared with the good healing group (P < 0.05). CONCLUSION: CDFI/PDU is an easy, painless, and effective method for predicting the prognosis of humeral shaft fractures by estimating early healing. PMID- 27277242 TI - Sonographic evaluation of anterior cervical lymph nodes. AB - PURPOSE: In this study we evaluated the role of ultrasound in diagnosis of anterior cervical lymph (ACL) node disease. METHODS: Three-hundred and sixty-six patients were included in the study. When ACL nodes were found, we noted the station(s) involved, the number, and the short and long axis of each. Patients had their thyroid investigated and were then divided into four groups: no sonographic signs of thyroid abnormality, already diagnosed autoimmune thyroiditis, probable new diagnosis of autoimmune thyroiditis, and thyroid nodules. RESULTS: ACL nodes were found in 127 out of 366 patients examined. The 127 patients with ACL nodes were classified into group 1 (2 patients), group 2 (97 patients), group 3 (23 patients), and group 4 (5 patients). The only differences were the presence and number of lymph nodes in the prelaryngeal and/or prethyroidal and/or pretracheal stations, and the number of "acutely inflamed" nodes in group 3 compared with all the other groups. CONCLUSION: We observed a strong association between anterior cervical lymphadenopathy and autoimmune thyroiditis; this is certainly a good reason to justify thorough evaluation of anterior cervical lymph nodes for all patients with suspected thyroiditis. PMID- 27277243 TI - A case of mucinous cystic neoplasm of the liver: description of Sonazoid-enhanced ultrasound imaging and histopathologic findings. AB - Mucinous cystic neoplasms (MCNs) of the hepatobiliary system are rare tumors that usually arise within the liver. We encountered a 63-year-old woman with a surgically proven MCN of the liver. We first performed contrast-enhanced ultrasound imaging, and the mass was found to have the appearance of a solid tumor, showing peripheral nodular enhancement in the arterial and portal phases with persistence of enhancement. The lesion remained enhanced in the post vascular phase (Kupffer phase). Based on these findings, we incorrectly identified the tumor as a cavernous hemangioma, despite negative findings in computed tomography and magnetic resonance imaging. In our immunohistologic analysis using anti-CD68 antibody, the antibody-positive cells were identified as macrophages. Therefore, the Sonazoid microbubbles could have been retained within these macrophages, resulting in late enhancement. These findings appear to be of key importance in accurately diagnosing MCNs and clarifying their pathophysiology. PMID- 27277245 TI - A case report of umbilical ring constriction with application of amnioinfusion. AB - This is a case report of a pregnant 38-year-old primigravida woman. Due to severe fetal growth restriction and oligohydramnios, she was referred to our tertiary perinatal center at 24 weeks' gestation. To rule out chromosomal abnormalities and facilitate ultrasound evaluation of fetal morphology, we performed amniocentesis and subsequent amnioinfusion. Thereafter, a precise ultrasound examination revealed no obvious fetal morphological abnormalities except for a hyper-coiled cord and marginal placenta previa. During expectant management, the amount of amniotic fluid was maintained at 20-26 mm for a few days; however, the pregnancy resulted in intrauterine fetal death after 26 weeks + 5 days of gestation. The stillborn infant weighed 530 g (-3.3 SD) and had no obvious external abnormalities apart from umbilical ring constriction. Although a postmortem autopsy was not performed, it is suspected that the fetal growth restriction and the intrauterine fetal death were associated with the hyper coiled cord and the umbilical ring constriction. It is thought that umbilical ring constriction might therefore be an irreversible fatal condition in cases with a hyper-coiled cord. PMID- 27277244 TI - Ultrasonography of intrahepatic bile duct adenoma with renal cell carcinoma: correlation with pathology. AB - Intrahepatic bile duct adenoma (BDA) is a relatively rare benign tumor. Most cases are incidentally discovered during surgery or autopsy. We report here the co-existence of renal cell carcinoma and BDA mimicking metastasis in a 30-year old female. An isoechoic nodule with a hypoechoic rim sized 10 * 9 mm was observed by ultrasonography in S2 of the liver. On contrast-enhanced ultrasonography (CEUS), the mass was enhanced in the early vascular phase and a defect with a clear border appeared in the post-vascular phase. We present the ultrasonography findings of BDA, including those yielded by CEUS using Sonazoid, along with the gross and microscopic pathological correlation. PMID- 27277246 TI - Prenatal diagnosis of persistent left and absent right superior vena cava. AB - We report a case of persistent left superior vena cava (LSVC) with absent right superior vena cava (RSVC) diagnosed prenatally. At 27 weeks' gestation, routine fetal ultrasonography showed an abnormal four-chamber view. Fetal echocardiography revealed a markedly enlarged coronary sinus in the four-chamber view. An absent RSVC and a persistent LSVC were demonstrated in the three-vessel view. No additional cardiac malformations were seen before birth. Postnatal imaging confirmed the prenatal diagnosis. The combination of persistent LSVC and absent RSVC without any other cardiac malformations is an extremely rare cardiac anomaly and less commonly detected in utero. Identification of a dilated coronary sinus in the four-chamber view, with atypical features in the three-vessel view, may lead to the antenatal diagnosis of this condition. PMID- 27277247 TI - Morphological changes observed via fetal ultrasound in prenatally diagnosed and isolated congenital lymphangiomas: three case reports. AB - We illustrate three cases of isolated congenital lymphangioma (CL). Fetal ultrasound (US) demonstrated uniloculated cystic masses that changed to multiloculated, subcutaneous, hypoechoic, avascular cystic masses with thin septations without solid components. Case 1: CL of the right forearm; Case 2: CL of the right hypochondrium; and Case 3: CL of the left upper posterior back. Postnatal US detected multiloculated, subcutaneous, hypoechoic, avascular cystic masses with thin septations without solid components or invasive developments. We prenatally and postnatally diagnosed them as isolated CL cases due to focal, soft, bulging masses with unclear margins. Due to our correct diagnosis and precise evaluation of sizes and locations, no perinatal complications occurred. In this case series, uniloculated features changed to multiloculated features and the largest macrocyst size decreased, whereas the sizes of the smaller microcysts increased. These morphological changes observed via fetal US represent intermittent CL growing processes. PMID- 27277248 TI - Three- and four-dimensional HDlive rendering image of fetal acrania/exencephaly in early pregnancy. AB - We present two cases of fetal acrania/exencephaly reconstructed employing the three- (3D) and four-dimensional (4D) HDlive rendering mode in early gestation. Two fetuses with acrania/exencephaly were studied with the 3D/4D HDlive rendering mode at 13 and 15 weeks, respectively. In Case 1, at 13 weeks' gestation, deformed and degenerated brain tissues were clearly shown using the 3D/4D HDlive rendering mode. In Case 2, at 15 weeks and 6 days of gestation, two amniotic bands and acrania/exencephaly were depicted with the 3D/4D HDlive rendering mode. Fragile brain hemispheres with amniotic bands were rocking with fetal movements. The 3D/4D HDlive rendering mode provides physicians, couples, and their families with important and additional information, and has the potential to supplement two-dimensional and conventional 3D ultrasound in diagnosing fetal acrania/exencephaly. PMID- 27277249 TI - Antenatal three-dimensional sonographic diagnosis of persistent cloaca. AB - We present a case of fetal persistent cloaca diagnosed by two- (2D) and three dimensional (3D) sonography and the HDlive rendering mode. 2D sonography revealed a bicornate uterus with hydrometra, bilateral hydrosalpinx, a single umbilical artery, and ascites. 3D sonography and the HDlive rendering mode clearly showed these intra-abdominal structures. To the best of our knowledge, this is the first report of persistent cloaca employing antenatal 3D sonography and the HDlive rendering mode. PMID- 27277250 TI - Antenatal three-dimensional sonographic features of fetal biliary atresia. AB - We present antenatal three-dimensional (3D) sonographic features of fetal biliary atresia. A 38-year-old pregnant Japanese woman was referred to our ultrasound clinic because of a fetal intra-abdominal cyst at 19 weeks of gestation. Conventional two-dimensional (2D) sonography and 3D sonography with an inversion mode showed a round cyst with a tiny dip in the subhepatic area. At 34 weeks, conventional 2D sonography and 3D sonography with inversion and transparent X-ray modes clearly revealed a round to oval cyst connected with the gallbladder via the cystic duct. A diagnosis of choledochal cyst (type I) was suggested antenatally. However, the final diagnosis made by employing operative cholangiography during surgery was biliary atresia (type I cyst) at 25 days of life. To the best of our knowledge, this is the first report of biliary atresia employing antenatal 3D sonography with inversion and transparent X-ray modes. PMID- 27277251 TI - A case of aggressive angiomyxoma of the vulva. AB - Aggressive angiomyxoma (AA) is a rare mesenchymal neoplasm of the female pelvis and vulva, which has a tendency for local recurrence. AA is occasionally misdiagnosed as Bartholin's gland cyst or abscess, lipoma, simple labial cyst, or soft tissue tumors. We describe a case of AA on the outside of the left labium majus pudendi in a 28-year-old female. We were able to make the preoperative diagnosis of AA by magnetic resonance imaging (MRI) and ultrasound (US), and to perform complete surgical excision with a transperineal minimally invasive approach. The novelty of this case is the use of ultrasound for the diagnostic workup of the perineal tumor and determination of the incision line. PMID- 27277252 TI - Bleeding in abdominal cavity revealed by contrast-enhanced ultrasonography. PMID- 27277253 TI - Three-dimensional HDlive rendering images of the TRAP sequence in the first trimester: reverse end-diastolic umbilical artery velocity in a pump twin with an adverse pregnancy outcome. PMID- 27277254 TI - Three-dimensional HDlive rendering image of cystic hygroma. PMID- 27277255 TI - Evaluation of surgical strategy of conventional vs. percutaneous robot-assisted spinal trans-pedicular instrumentation in spondylodiscitis. AB - Robot-assisted percutaneous insertion of pedicle screws is a recent technique demonstrating high accuracy. The optimal treatment for spondylodiscitis is still a matter of debate. We performed a retrospective cohort study on surgical patients treated with pedicle screw/rod placement alone without the application of intervertebral cages. In this collective, we compare conventional open to a further minimalized percutaneous robot-assisted spinal instrumentation, avoiding a direct contact of implants and infectious focus. 90 records and CT scans of patients treated by dorsal transpedicular instrumentation of the infected segments with and without decompression and antibiotic therapy were analysed for clinical and radiological outcome parameters. 24 patients were treated by free hand fluoroscopy-guided surgery (121 screws), and 66 patients were treated by percutaneous robot-assisted spinal instrumentation (341 screws). Accurate screw placement was confirmed in 90 % of robot-assisted and 73.5 % of free-hand placed screws. Implant revision due to misplacement was necessary in 4.95 % of the free hand group compared to 0.58 % in the robot-assisted group. The average intraoperative X-ray exposure per case was 0.94 +/- 1.04 min in the free-hand group vs. 0.4 +/- 0.16 min in the percutaneous group (p = 0.000). Intraoperative adverse events were observed in 12.5 % of free-hand placed pedicle screws and 6.1 % of robot robot-assisted screws. The mean postoperative hospital stay in the free-hand group was 18.1 +/- 12.9 days, and in percutaneous group, 13.8 +/- 5.6 days (p = 0.012). This study demonstrates that the robot-guided insertion of pedicle screws is a safe and effective procedure in lumbar and thoracic spondylodiscitis with higher accuracy of implant placement, lower radiation dose, and decreased complication rates. Percutaneous spinal dorsal instrumentation seems to be sufficient to treat lumbar and thoracic spondylodiscitis. PMID- 27277256 TI - Trial Validates Biosimilar for Trastuzumab. AB - Preliminary data from the phase III Heritage trial suggest that a biosimilar to trastuzumab, MYL-14010, is just as safe and effective as its brand-name equivalent for women with HER2-positive advanced breast cancer. The findings, presented during the annual meeting of the American Society of Clinical Oncology in June, may pave the way for the first FDA-approved biosimilar for cancer. PMID- 27277257 TI - Treating Tumors by Molecular Profile, Not Type. AB - Preliminary findings from MyPathway, an ongoing phase II basket trial, indicate that matching molecular abnormalities of patients' tumors to relevant targeted therapies-albeit outside a given drug's FDA-approved indication-is both feasible and promising. Notably, patients with HER2-amplified colorectal, bladder, and biliary cancers responded well to the combination of trastuzumab and pertuzumab. PMID- 27277259 TI - Assessing pediatric ileocolonic Crohn's disease activity based on global MR enterography scores. AB - OBJECTIVES: This study was aimed at correlating a magnetic resonance index of activity (MaRIA) and a magnetic resonance enterography global score (MEGS) with activity indexes in a paediatric population with Crohn's disease (CD). METHODS: This retrospective study included 32 paediatric patients (median age 14.5 years, 18 male) with proven CD who underwent magnetic resonance enterography (MRE). A correlation analysis was performed on the MRE-based scores, the simplified endoscopic score for CD (SES-CD), the paediatric Crohn's disease activity index (PCDAI), and C-reactive protein (CRP) levels. Based on PCDAI, comparison of both global MaRIA and MEGS was made between patients with mild and moderate/severe disease activity. RESULTS: Global MaRIA correlated with SES-CD (r = 0.70, p = 0.001) and PCDAI (r = 0.42, p = 0.016). MEGS correlated with PCDAI (r = 0.46, p = 0.007) and CRP levels (r = 0.35, p = 0.046). MEGS differed significantly (p = 0.027) between patients grouped by clinical disease severity. CONCLUSIONS: MRE based global scores correlated with clinical indexes of CD activity. Therefore, they represent a potential useful tool to predict CD activity and severity, as well as a possible promising alternative to endoscopy, to monitor paediatric patients with CD during their follow-up. KEY POINTS: * MRE is widely used to for accurate assessment of CD. * Global MaRIA and MEGS have been suggested as indicators of CD activity. * Paediatric studies comparing MRE-based global scores with clinical CD activity are lacking. * Such scores can serve as predictors of CD activity/severity in paediatric patients. * MRE offers an alternative to clinical score/endoscopy for paediatric CD monitoring. PMID- 27277258 TI - MicroRNA-142-5p contributes to Hashimoto's thyroiditis by targeting CLDN1. AB - BACKGROUND: MicroRNAs have the potential as diagnostic biomarkers and therapeutic targets in autoimmune diseases. However, very limited studies have evaluated the expression of microRNA profile in thyroid gland related to Hashimoto's thyroiditis (HT). METHODS: MicroRNA microarray expression profiling was performed and validated by quantitative RT-PCR. The expression pattern of miR-142-5p was detected using locked nucleic acid-in situ hybridization. The target gene was predicted and validated using miRNA targets prediction database, gene expression analysis, quantitative RT-PCR, western blot, and luciferase assay. The potential mechanisms of miR-142-5p were studied using immunohistochemistry, immunofluorescence, and quantitative assay of thyrocyte permeability. RESULTS: Thirty-nine microRNAs were differentially expressed in HT (Fold change >=2, P < 0.05) and miR-142-5p, miR-142-3p, and miR-146a were only high expression in HT thyroid gland (P < 0.001). miR-142-5p, which was expressed at high levels in injured follicular epithelial cells, was also detected in HT patient serum and positively correlated with thyroglobulin antibody (r >= 0.6, P < 0.05). Furthermore, luciferase assay demonstrated CLDN1 was the direct target gene of miR-142-5p (P < 0.05), and Immunohistochemical staining showed a reverse expression patterns with miR-142-5p and CLDN1. Overexpression of miR-142-5p in thyrocytes resulted in reducing of the expression of claudin-1 both in mRNA and protein level (P = 0.032 and P = 0.009 respectively) and increasing the permeability of thyrocytes monolayer (P < 0.01). CONCLUSIONS: Our findings indicate a previously unrecognized mechanism that miR-142-5p, targeting CLDN1, plays an important role in HT pathogenesis. PMID- 27277260 TI - Do quantitative and qualitative shear wave elastography have a role in evaluating musculoskeletal soft tissue masses? AB - OBJECTIVES: To determine if quantitative and qualitative shear wave elastography have roles in evaluating musculoskeletal masses. METHODS: 105 consecutive patients, prospectively referred for biopsy within a specialist sarcoma centre, underwent B-mode, quantitative (m/s) and qualitative (colour map) shear wave elastography. Reference was histology from subsequent biopsy or excision where possible. Statistical modelling was performed to test elastography data and/or B mode imaging in predicting malignancy. RESULTS: Of 105 masses, 39 were malignant and 6 had no histology but benign characteristics at 12 months. Radiologist agreement for B-mode and elastography was moderate to excellent Kw 0.52-0.64; PABAKw 0.85-0.90). B-Mode imaging had 78.8% specificity, 76.9% sensitivity for malignancy. Quantitatively, adjusting for age, B-mode and lesion volume there was no statistically significant association between longitudinal velocity and malignancy (OR [95% CI] 0.40[0.10, 1.60], p=0.193), but some evidence that higher transverse velocity was associated with decreased odds of malignancy (0.28[0.06, 1.28], p=0.101). Qualitatively malignant masses tended to be towards the blue spectrum (lower velocities); 39.5% (17/43) of predominantly blue masses were malignant, compared to 14.3% (1/7) of red lesions. CONCLUSIONS: Quantitatively and qualitatively there is no statistically significant association between shear wave velocity and malignancy. There is no clear additional role to B-mode imaging currently. KEY POINTS: * Correlation between shear wave velocity and soft tissue malignancy was statistically insignificant * B-mode ultrasound is 76.9 % sensitive and 78.8 % specific * Statistical models show elastography does not significantly add to lesion assessment. PMID- 27277263 TI - The dilemma surrounding nuchal translucency-thickness measurement in Japan. PMID- 27277262 TI - The effectiveness of nutrition education for overweight/obese mothers with stunted children (NEO-MOM) in reducing the double burden of malnutrition in Indonesia: study protocol for a randomized controlled trial. AB - BACKGROUND: Nutrition transition in developing countries were induced by rapid changes in food patterns and nutrient intake when populations adopt modern lifestyles during economic and social development, urbanization and acculturation. Consequently, these countries suffer from the double burden of malnutrition, consisting of unresolved undernutrition and the rise of overweight/obesity. The prevalence of the double burden of malnutrition tends to be highest for moderate levels (third quintile) of socioeconomic status. Evidence suggests that modifiable factors such as intra-household food distribution and dietary diversity are associated with the double burden of malnutrition, given household food security. This article describes the study protocol of a behaviorally based nutrition education intervention for overweight/obese mothers with stunted children (NEO-MOM) in reducing the double burden of malnutrition. METHODS: NEO-MOM is a randomized controlled trial with a three-month behavioral intervention for households involving pairs of 72 stunted children aged 2-5 years old and overweight/obese mothers (SCOWT) in urban Indonesia. The SCOWT pairs were randomly assigned to either an intervention group or to a comparison group that received usual care plus printed educational materials. The intervention consisted of six classroom sessions on nutrition education and home visits performed by trained community health workers using a motivational interviewing approach. The primary outcomes of this study are the prevalence of double burden of malnutrition as measured in SCOWT, child's height-for-age z-score (HAZ) and maternal body mass index (BMI). DISCUSSION: Because previous studies are mainly observational in nature, this study advances understanding of the double burden of malnutrition through a fully powered randomized controlled trial. The intervention assists participants in self-administered goal setting to improve diet and child feeding behaviors by improving self-efficacy. Maternal self efficacy may be enhanced through vicarious and active mastery of experiences gained during six sessions of nutrition education and verbal persuasion during home visits. TRIAL REGISTRATION: The Universal Trial Number (UTN) for this study is U1111-1175-5834. This trial was registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) and is allocated the registration number: ACTRN12615001243505 on 12 November 2015. PMID- 27277264 TI - Moment-based texture segmentation of luminal contour in intravascular ultrasound images. AB - PURPOSE: A system for luminal contour segmentation in intravascular ultrasound images is proposed. METHODS: Moment-based texture features are used for clustering of the pixels in the input image. After the clustering, morphological smoothing and a boundary detection process are applied and the final image is obtained. RESULTS: The proposed method was applied to 15 images from different patients, and a correlation coefficient of 0.86 was obtained between the areas of lumen automatically and manually defined. CONCLUSION: Moment-based texture features together with the radial feature are powerful tools for identification of the lumen region in intravascular ultrasound images. Morphological filtering was useful for improving the segmentation results. PMID- 27277261 TI - Advanced-stage hepatocellular carcinoma with portal vein thrombosis: conventional versus drug-eluting beads transcatheter arterial chemoembolization. AB - OBJECTIVES: Our study sought to compare the overall survival in patients with hepatocellular carcinoma (HCC) and portal venous thrombosis (PVT), treated with either conventional trans-arterial chemoembolization (cTACE) or drug-eluting beads (DEB) TACE. METHODS: This retrospective analysis included a total of 133 patients, treated without cross-over and compared head-to-head by means or propensity score weighting. Mortality was compared using survival analysis upon propensity score weighting. Adverse events and liver toxicity grade >=3 were recorded and reported for each TACE. In order to compare with historical sorafenib studies, a sub-group analysis was performed and included patients who fulfilled the SHARP inclusion criteria. RESULTS: The median overall survival (MOS) of the entire cohort was 4.53 months (95 % CI, 3.63-6.03). MOS was similar across treatment arms, no significant difference between cTACE (N = 95) and DEB TACE (N = 38) was observed (MOS of 5.0 vs. 3.33 months, respectively; p = 0.157). The most common adverse events after cTACE and DEB- TACE, respectively, were as follows: post-embolization syndrome [N = 57 (30.0 %) and N = 38 (61.3 %)], diarrhea [N = 3 (1.6 %) and N = 3 (4.8 %)], and encephalopathy [N = 11 (5.8 %) and N = 2 (3.2 %)]. CONCLUSION: Our retrospective study could not reveal a difference in toxicity and efficiency between cTACE and DEB-TACE for treatment of advanced stage HCC with PVT. KEY POINTS: * Conventional TACE (cTACE) and drug eluting-beads TACE (DEB-TACE) demonstrated equal safety profiles. * Survival rates after TACE are similar to patients treated with sorafenib. * Child-Pugh class and tumor burden are reliable predictors of survival. PMID- 27277265 TI - Contribution of the renin-angiotensin system to the intrarenal resistive index in chronic unilateral partial ureteral obstruction in dogs. AB - PURPOSE: We investigated the role of the renin-angiotensin system on intrarenal hemodynamics in chronic unilateral partial ureteral obstruction (UPUO) using Doppler ultrasound (US). METHODS: In 11 dogs with chronic UPUO, we determined the renal resistive index (RI) before and 1 h after the intravenous infusion of an angiotensin-converting enzyme (ACE) inhibitor (captopril), an angiotensin II receptor type 1 (ART1) antagonist (L-158,809), and the combination of these two drugs. Change in resistive index (DeltaRI) was calculated as RI after the administration of each tested material minus baseline RI. RESULTS: At the baseline measurement, significant differences in RI were seen between obstructed and nonobstructed kidneys. ACE inhibitor, ART1 antagonist, or the combination of these drugs did not result in any significant changes in RI in either obstructed or nonobstructed kidneys. However, in obstructed kidneys, DeltaRI in the combination of ACE inhibitor and ART1 antagonist were significantly greater than those in ACE inhibitor or ART1 antagonist alone, whereas there were no significant differences in those values in nonobstructed kidneys. CONCLUSION: These observations suggest that the renin-angiotensin system in dogs with chronic UPUO may not contribute significantly to the differences in intrarenal RI between obstructed and nonobstructed kidneys. However, the angiotensin-producing pathways and angiotensin II receptor subtypes other than ACE and ART1 may have some different effects between obstructed and nonobstructed kidneys. PMID- 27277266 TI - Evaluation of transcatheter arterial embolization therapy on hepatocellular carcinomas using contrast-enhanced harmonic power Doppler sonography: comparison with CT, power Doppler sonography, and dynamic MRI. AB - PURPOSE: The aim of this study was to assess and compare the sensitivity of power Doppler sonography, contrast-enhanced sonography, plain computed tomography (CT), and dynamic magnetic resonance imaging (MRI) for detecting hepatocellular carcinoma (HCC) nodules incompletely treated with transcatheter arterial embolization (TAE). METHODS: A total of 63 unresectable HCC nodules were examined in this study. The HCCs were treated with TAE. All patients underwent plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI 1 week after TAE. The sensitivity of each modality to incompletely treated HCC nodules was compared. Detection of the residual viable HCC on angiography or tumor biopsy was regarded as the gold standard for the diagnosis of incomplete treatment. RESULTS: Twenty-four nodules (38%) were diagnosed as incompletely treated. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these incompletely treated nodules were 42% (10/24), 46% (11/24), 88% (21/24), and 79% (19/24), respectively. Eighty percent (19 nodules) of the 24 incompletely treated nodules were located within a depth of less than 8 cm. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these superficial incompletely treated nodules were 37% (7/19), 53% (10/19), 100% (19/19), and 74% (14/19), respectively. In contrast, the sensitivities of each modality to deeply located nodules were 60% (3/5), 20% (1/5), 40% (2/5), and 100% (5/5), respectively. CONCLUSION: Plain CT and power Doppler sonography had a low sensitivity to HCC nodules incompletely treated with TAE. Except for those that were deeply located, contrast-enhanced harmonic sonography showed the highest sensitivity in detecting incompletely treated HCC nodules. PMID- 27277267 TI - Congenital diaphragmatic hernia: an evaluation of the prognostic value of the lung-to-head ratio. AB - PURPOSE: A retrospective analysis of the prognostic significance of the lung-to head ratio (LHR) on the outcome of fetuses with left-sided congenital diaphragmatic hernia (CDH). METHODS: A total of 12 fetuses with isolated left CDH without any chromosomal abnormalities were included in this study. Twelve LHR measurements could retrospectively be calculated from the last available ultrasonographic recordings before birth. The relationship between the LHR and fetal outcome and gestational age was investigated. The cutoff levels as previously published were applied to determine their predictive value in this population. The association between other prenatal predictive variables and the fetal outcome was also determined. Survival was defined as being discharged from the hospital. RESULTS: The overall survival rate was 75%, and a statistically significant difference was observed between the mean LHR of the survivors and the mean LHR of the nonsurvivors (1.81 vs. 0.43), whereas the mean gestational age of these two groups did not differ. The LHR was not gestational age dependent with regard to its ability to predict the fetal outcome. The cutoff levels LHR <1, 1 1.4, and >1.4 showed good applicability for predicting fetal outcome within the present study population, with 100% survival if LHR >1.4 and 75% mortality if LHR <1. The intrathoracic position of the stomach, mediastinal shift, and polyhydramnios as individual variables and early diagnosis (<25 weeks gestation) all turned out to be poor sonographic predictors of fetal outcome. CONCLUSION: The LHR proved to be a good predictor of fetal outcome, independent of gestational age at the time of measurement. To further substantiate our observations, a prospective multicenter study is warranted. PMID- 27277268 TI - A case of splenosis: diagnosis with contrast-enhanced ultrasonography. AB - We performed contrast-enhanced ultrasonography (CEUS) for a patient with known splenosis. One mass was clearly enhanced while another mass showed moderate enhancement. The right kidney showed similar enhancement and was a little confusing. We concluded that CEUS is useful for diagnosing this entity, although it has some limitations. CEUS could be a better diagnostic option than scintigraphic studies. PMID- 27277269 TI - A Christmas-tree-like mass in the urinary bladder. PMID- 27277270 TI - 2005 Guidelines for ultrasonic diagnosis of breast diseases regarding the mass image-forming types. PMID- 27277271 TI - New Outstanding Paper Award to accompany the Kikuchi Award. PMID- 27277272 TI - Defensive Medicine Among Plastic and Aesthetic Surgeons in Israel. AB - BACKGROUND: Defensive medicine (DM) includes medical practices that are aimed at avoiding liability rather than benefitting the patient. DM has not been well characterized among plastic surgeons. OBJECTIVES: The authors examined the extents of intended and unintended DM among members of the Israeli Society of Plastic and Aesthetic Surgery (ISPAS) and identified risk factors for DM. METHODS: A total of 108 ISPAS members were asked to complete a questionnaire that addressed physician attitudes toward DM and intended or unintended DM practices. RESULTS: Seventy-eight surgeons (72.2% response rate) returned the questionnaire, although some questionnaires were returned incomplete. Forty respondents acknowledged practicing DM (ie, DM group), and 33 respondents did not (ie, non-DM group). There were no between-group differences in gender, years of practice, or number of previous litigations. Thirty-one percent of respondents in the DM group indicated that they avoid certain surgical procedures, compared with 6% of respondents in the non-DM group (P = .008). In private practice, 66.2% of respondents stated that they obtain written informed consent twice before surgery, and 100% request preoperative blood-coagulation testing. In contrast, 40% and 74% of respondents in public practice, respectively, acknowledged these behaviors (for consent, P = .027; for testing, P = .0059). Sixty-three percent of respondents prescribe antibiotics for more than 24 hours postoperatively, and this practice was slightly more common in the DM group (34 prescribe antibiotics vs 21 in the non-DM group; P = .079). CONCLUSIONS: DM is highly integrated into the daily medical practices of plastic surgeons in Israel. PMID- 27277273 TI - Barbed Suture Rescue Procedure. PMID- 27277274 TI - Anatomical Study of the Lateral Crural Strut Graft in Rhinoplasty and Its Clinical Application. AB - BACKGROUND: Lateral crural strut graft has been used in rhinoplasty to correct deformities such as bulbous nasal tip, lateral crus malposition, alar retraction, collapsed external valve, lateral crus concavity, and alar deformity after domal suture. Despite its widespread use, the lateral crural strut graft has not been the subject of studies that show its benefits objectively and statistically. OBJECTIVES: To assess nasal anatomical variations in cadavers that underwent rhinoplasty using the lateral crural strut graft, considering the clinical applications of this graft. METHODS: The study was conducted with 16 human cadavers that underwent rhinoplasty with lateral crural strut graft. The variables were basilar nasal width, interalar width, columella-nasal tip height, nostril's width, and length and width of the graft. Measurements were taken with a digital caliper before and after rhinoplasty, and nostril cross-sectional area was measured with a computer program. All measurements were submitted to statistical analysis. RESULTS: Most of the cadavers were young, male, and black. Variables values were increased, but only basilar nasal width, columella-nasal tip height, and nostril cross-sectional area showed statistically significant differences (P < .05), leading to changes in the alar base, the nasal tip projection and the external nasal valve. CONCLUSIONS: Lateral crural strut graft improves external nasal valve and increases nasal tip projection and basilar nasal width. PMID- 27277275 TI - Use of the "Septal T" as a Spacer and Conformer for a Properly Contoured Nasal Tip in Rhinoplasty. PMID- 27277276 TI - Commentary on: Who is Publishing in Facial Cosmetic Surgery? A Citation Analysis Across Specialties Over Five Decades. PMID- 27277277 TI - HOSVD-Based 3D Active Appearance Model: Segmentation of Lung Fields in CT Images. AB - An Active Appearance Model (AAM) is a computer vision model which can be used to effectively segment lung fields in CT images. However, the fitting result is often inadequate when the lungs are affected by high-density pathologies. To overcome this problem, we propose a Higher-order Singular Value Decomposition (HOSVD)-based Three-dimensional (3D) AAM. An evaluation was performed on 310 diseased lungs form the Lung Image Database Consortium Image Collection. Other contemporary AAMs operate directly on patterns represented by vectors, i.e., before applying the AAM to a 3D lung volume,it has to be vectorized first into a vector pattern by some technique like concatenation. However, some implicit structural or local contextual information may be lost in this transformation. According to the nature of the 3D lung volume, HOSVD is introduced to represent and process the lung in tensor space. Our method can not only directly operate on the original 3D tensor patterns, but also efficiently reduce the computer memory usage. The evaluation resulted in an average Dice coefficient of 97.0 % +/- 0.59 %, a mean absolute surface distance error of 1.0403 +/- 0.5716 mm, a mean border positioning errors of 0.9187 +/- 0.5381 pixel, and a Hausdorff Distance of 20.4064 +/- 4.3855, respectively. Experimental results showed that our methods delivered significant and better segmentation results, compared with the three other model-based lung segmentation approaches, namely 3D Snake, 3D ASM and 3D AAM. PMID- 27277278 TI - Healthcare Hackathons Provide Educational and Innovation Opportunities: A Case Study and Best Practice Recommendations. AB - Physicians and other healthcare professionals are often the end users of medical innovation; however, they are rarely involved in the beginning design stages. This often results in ineffective healthcare solutions with poor adoption rates. At the early design stage, innovation would benefit from input from healthcare professionals. This report describes the first-ever rehabilitation hackathon-an interdisciplinary and competitive team event aimed at accelerating and improving healthcare solutions and providing an educational experience for participants. Hackathons are gaining traction as a way to accelerate innovation by bringing together a diverse group of interdisciplinary professionals from different industries who work collaboratively in teams and learn from each other, focus on a specific problem ("pain point"), develop a solution using design thinking techniques, pitch the solution to participants, gather fast feedback and quickly alter the prototype design ("pivoting"). 102 hackers including 19 (18.6 %) physicians and other professionals participated, and over the course of 2 days worked in teams, pitched ideas and developed design prototypes. Three awards were given for prototypes that may improve function in persons with disabilities. 43 hackers were women (42.2 %) and 59 men (57.8 %); they ranged in age from 16 to 79 years old; and, of the 75 hackers who reported their age, 63 (84 %) were less than 40 years old and 12 (16 %) were 40 years or older. This report contributes to the emerging literature on healthcare hackathons as a means of providing interdisciplinary education and training and supporting innovation. PMID- 27277279 TI - (11)C-Choline PET/CT for restaging prostate cancer. Results from 4,426 scans in a single-centre patient series. AB - PURPOSE: To evaluate (11)C-choline PET/CT as a diagnostic tool for restaging prostate cancer (PCa), in a large, homogeneous and clinically relevant population of patients with biochemical recurrence (BCR) of PCa after primary therapy. The secondary aim was to assess the best timing for performing (11)C-choline PET/CT during BCR. METHODS: We retrospectively analysed 9,632 (11)C-choline PET/CT scans performed in our institution for restaging PCa from January 2007 to June 2015. The inclusion criteria were: (1) proven PCa radically treated with radical prostatectomy (RP) or with primary external beam radiotherapy (EBRT); (2) PSA serum values available; (3) proven BCR (PSA >0.2 ng/mL after RP or PSA >2 ng/mL above the nadir after primary EBRT with rising PSA levels). Finally, 3,203 patients with recurrent PCa matching all the inclusion criteria were retrospectively enrolled and 4,426 scans were analysed. RESULTS: Overall, 52.8 % of the (11)C-choline PET/CT scans (2,337/4,426) and 54.8 % of the patients (1,755/3,203) were positive. In 29.4 % of the scans, at least one distant finding was observed. The mean and median PSA values were, respectively, 4.9 and 2.1 ng/mL at the time of the scan (range 0.2 - 50 ng/mL). In our series, 995 scans were performed in patients with PSA levels between 1 and 2 ng/mL. In this subpopulation the positivity rate in the 995 scans was 44.7 %, with an incidence of distant findings of 19.2 % and an incidence of oligometastatic disease (one to three lesions) of 37.7 %. The absolute PSA value at the time of the scan and ongoing androgen deprivation therapy were associated with an increased probability of a positive (11)C-choline PET/CT scan (p < 0.0001). In the ROC analysis, a PSA value of 1.16 ng/mL was the optimal cut-off value. In patients with a PSA value <1.16 ng/mL, 26.8 % of 1,426 (11)C-choline PET/CT scans were positive, with oligometastatic disease in 84.7 % of positive scans. CONCLUSION: In a large cohort of patients, the feasibility of (11)C-choline PET/CT for detecting the sites of metastatic disease in PCa patients with BCR was confirmed. The PSA level was the main predictor of a positive scan with 1.16 ng/mL as the optimal cut-off value. In the majority of positive scans oligometastatic disease, potentially treatable with salvage therapies, was observed. PMID- 27277280 TI - Potent Protection Against MPP+-Induced Neurotoxicity via Activating Transcription Factor MEF2D by a Novel Derivative of Naturally Occurring Danshensu/Tetramethylpyrazine. AB - Danshensu (DSS) and tetramethylpyrazine (TMP) are active ingredients of Salvia miltiorrhiza Bge. and Ligusticum chuanxiong Hort that are widely used in oriental medicine. Structural combination of compounds with known biological activity may lead to the formation of a molecule with multiple properties or new function profile. In the current study, the neuroprotective effects of DT-010, a novel analogue in which TMP was coupled to DSS through an ester bond and two allyl groups at the carboxyl group, were evaluated in a cellular model of Parkinson's disease (PD). As evidenced by the increase in cell survival, as well as the decrease in the number of Hoechst-stained apoptotic nuclei and the level of intracellular accumulation of reactive oxygen species, DT-010 at 3-30 uM substantially protected against MPP+-induced neurotoxicity in both PC12 cells and primary cerebellar granule neurons, a protection that was more potent and efficacious than its parent molecules DSS and TMP. Very encouragingly, we found that DT-010, but not DSS or TMP, could enhance myocyte enhancer factor 2D (MEF2D) transcriptional activity using luciferase reporter gene assay. The neuroprotective effects of DT-010 could be blocked by pharmacologic inhibition of PI3K pathways with LY294002, or MEF2D pathway with short hairpin RNA-mediated knockdown of MEF2D. Furthermore, western blot analysis revealed that DT-010 potentiates Akt protein expression against MPP+ to down-regulate MEF2D inhibitor GSK3beta. Taken together, the results suggest that DT-010 prevents MPP+-induced neurotoxicity via enhancing MEF2D through the activation of PI3K/Akt/GSK3beta pathway. DT-010 may be a potential candidate for further preclinical study for preventing and treating PD. PMID- 27277281 TI - Signal and Noise in the Perception of Facial Emotion Expressions: From Labs to Life. AB - Human interactions are replete with emotional exchanges, and hence, the ability to decode others' emotional expressions is of great importance. The present research distinguishes between the emotional signal (the intended emotion) and noise (perception of secondary emotions) in social emotion perception and investigates whether these predict the quality of social interactions. In three studies, participants completed laboratory-based assessments of emotion recognition ability and later reported their perceptions of naturally occurring social interactions. Overall, noise perception in the recognition task was associated with perceiving more negative emotions in others and perceiving interactions more negatively. Conversely, signal perception of facial emotion expressions was associated with higher quality in social interactions. These effects were moderated by relationship closeness in Greece but not in Germany. These findings suggest that emotion recognition as assessed in the laboratory is a valid predictor of social interaction quality. Thus, emotion recognition generalizes from the laboratory to everyday life. PMID- 27277282 TI - Pleasure From Another's Pain: The Influence of a Target's Hedonic States on Attributions of Immorality and Evil. AB - Can people's feelings about harm (i.e., their hedonic reactions) lead them to be morally condemned, even if they do not cause the harm themselves? We show that individuals who experience pleasure at serious harm that has befallen another person are judged both immoral and evil. This effect occurs for harm-causing actors, and for observers who play no role in causing the harm; actors can also be judged as immoral and evil when they experience mere indifference (Study 1). Observers are more likely to be similarly judged when they experience direct rather than indirect pleasure from harm caused to another (Study 2). The effects of pleasure are dissociable from those of malevolent desires (Study 3). Targets' experience of pleasure at the harm caused to another person leads to the social exclusion of observers (Studies 1-3) and the harsh punishment of actors, including the death penalty (Studies 1, 4a, and 4b). PMID- 27277283 TI - Reducing Stereotype Threat With Embodied Triggers: A Case of Sensorimotor-Mental Congruence. AB - In four experiments, we tested whether embodied triggers may reduce stereotype threat. We predicted that left-side sensorimotor inductions would increase cognitive performance under stereotype threat, because such inductions are linked to avoidance motivation among right-handers. This sensorimotor-mental congruence hypothesis rests on regulatory fit research showing that stereotype threat may be reduced by avoidance-oriented interventions, and motor congruence research showing positive effects when two parameters of a motor action activate the same motivational system (avoidance or approach). Results indicated that under stereotype threat, cognitive performance was higher when participants contracted their left hand (Study 1) or when the stimuli were presented on the left side of the visual field (Studies 2-4), as compared with right-hand contraction or right side visual stimulation. These results were observed on math (Studies 1, 2, and 4) and Stroop (Study 3) performance. An indirect effect of congruence on math performance through subjective fluency was also observed. PMID- 27277284 TI - Drinking to toxicity: college students referred for emergency medical evaluation. AB - BACKGROUND: In 2009, a university adopted a policy of emergency department transport of students appearing intoxicated on campus. The objective was to describe the change in ED referrals after policy initiation and describe a group of students at risk for acute alcohol-related morbidity. METHODS: A retrospective cohort of university students during academic years 2007-2011 (September-June) transported to local ED's was evaluated. Data were compared 2 years prior to initiation of the policy and 3 years after and included total number of ED transports and blood or breath alcohol level. RESULTS: 971 Students were transported to local ED's. The mean number of yearly transports 2 years prior to policy initiation was 131 and 3 years after was 236 (56 % increase, p < 0.01). 92 % had a blood or breath alcohol level obtained. The mean alcohol level was 193 mg/dL. Twenty percent of students had alcohol levels greater than 250 mg/dL. CONCLUSIONS: Adoption of a university alcohol policy was followed by a significant increase in ED transports of intoxicated students. College students identified as intoxicated frequently drank to toxicity. PMID- 27277286 TI - Activated carbon becomes active for oxygen reduction and hydrogen evolution reactions. AB - We utilized a facile method for creating unique defects in the activated carbon (AC), which makes it highly active for the oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER). The ORR activity of the defective AC (D-AC) is comparable to the commercial Pt/C in alkaline medium, and the D-AC also exhibits excellent HER activity in acidic solution. PMID- 27277288 TI - The added value of real-time three-dimensional echocardiography in the diagnosis of supravalvar mitral ring: case report and review of the literature. AB - Supravalvular mitral stenosis is a rare condition characterized by an abnormal ridge, with one or two orifices, covering and obstructing the mitral valve. Preoperative identification of the supravalvular ring is the target for obtaining good surgical results. Two-dimensional echocardiogram and transesophageal echocardiography both failed in reaching this objective. In this case, we showed that three-dimensional echocardiogram is a new technique that provides additional and more accurate echocardiographic characterization of congenital supravalvular mitral stenosis. PMID- 27277289 TI - Quantification of mitral valve apparatus by three-dimensional transesophageal echocardiography: in vitro validation study comparing two different analysis systems. AB - BACKGROUND: Two commercial software systems have become available for quantitation of mitral leaflet and annulus geometry based on three-dimensional (3D) transesophageal echocardiographic (3DTEE) images. The aim of this study is to investigate the accuracy and compatibility of the three-dimensional (3D) measurements by Real View((r)) and MVQ((r)). METHODS: 3DTEE images were obtained from phantom models with saddle-shaped annulus of mitral valve prolapse and mitral valve tenting. From reconstructed 3D data, prolapse and tenting volume were calculated by both Real View((r)) and MVQ((r)) and compared with the actual volume. RESULTS: The volume of the phantom models with saddle-shaped annulus measured by Real View((r)) (tenting r = 0.99, prolapse r = 0.99) and MVQ((r)) (tenting r = 0.99, prolapse r = 0.99) showed good agreement with the actual volume. However, significant difference between Real View((r)) and MVQ((r)) was observed in the result of quantification (tenting 2.27 +/- 1.5 ml versus 2.53 +/- 1.6 ml, prolapse 2.55 +/- 1.7 ml versus 2.31 +/- 1.6 ml, both P < 0.05). CONCLUSIONS: Although the 2 commercially available systems allow accurate quantitative measurements of the 3D volume, discrepancy in the quantified value as a result of differences in the estimation of annular level is observed. Therefore, we should take into account the characteristics of each software when interpreting analytical results. PMID- 27277287 TI - Molecular Pathophysiology of Fragile X-Associated Tremor/Ataxia Syndrome and Perspectives for Drug Development. AB - Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder manifesting in carriers of 55 to 200 CGG repeats in the 5' untranslated region (UTR) of the fragile X mental retardation gene (FMR1). FXTAS is characterized by enhanced FMR1 transcription and the accumulation of CGG repeat-containing FMR1 messenger RNA in nuclear foci, while the FMRP protein expression levels remain normal or moderately low. The neuropathological hallmark in FXTAS is the presence of intranuclear, ubiquitin-positive inclusions that also contain FMR1 transcript. Yet, the complete protein complement of FXTAS inclusions and the molecular events that trigger neuronal death in FXTAS remain unclear. In this review, we present the two most accepted toxicity mechanisms described so far, namely RNA gain-of-function and protein gain-of-function by means of repeat associated non-AUG translation, and discuss current experimental and computational strategies to better understand FXTAS pathogenesis. Finally, we review the current perspectives for drug development with disease-modifying potential for FXTAS. PMID- 27277290 TI - Noninvasive assessment of pulmonary vascular resistance and pressure in patients with congenital heart disease: a new method using M-mode echocardiography. AB - BACKGROUND: The accurate evaluation of pulmonary vascular resistance (PVR) and mean pulmonary artery pressure is important to determine the optimal management and therapeutic strategy for patients with congenital heart disease (CHD). We evaluated the PVR and mean pulmonary artery pressure in 46 patients with several CHD types using the interventricular septum (IVS) motion determined by M-mode echocardiography. METHODS: We divided the patients into 2 groups according to the different IVS motions. We measured the maximum anterior displacement from the baseline during early systole (a) and the maximum posterior displacement from the baseline during early diastole (b). We defined type A to be a/b greater than or equal to 1.0, and type B to be a/b less than 1.0. RESULTS: The PVR and mean pulmonary artery pressure in type A patients were significantly higher than those in type B patients (p < 0.05). Type A IVS motion predicted patients with high PVR (>2.5 unit/m(2)) and high mean pulmonary artery pressure (>25 mmHg) (sensitivity 89%, specificity 89% and sensitivity 70%, specificity 91%, respectively). CONCLUSIONS: Our method can noninvasively separate high and low PVR among patients with CHD. This noninvasive method is therefore considered to be useful in the management of patients with CHD in a clinical setting. PMID- 27277291 TI - Left coronary artery ostial stenosis from Takayasu's arteritis diagnosed using transthoracic color flow and pulsed Doppler echocardiography. AB - Coronary artery stenosis is seen in 10-45% of patients with Takayasu's arteritis (TA) and coronary ostia are most frequently involved. It may cause angina pectoris and sudden death during the early course of the disease. We describe a 14-year-old girl who first presented with exertional angina and syncope and was diagnosed as having left coronary artery ostial stenosis from TA by using transthoracic echocardiography. This is the first report showing the important role of color flow and pulsed Doppler echocardiography to detect coronary artery stenosis caused by TA. PMID- 27277292 TI - Prominent isovolumic relaxation flow in a patient with cardiac tamponade. AB - We present herein the case of a 72-year-old man who presented with orthopnea and was diagnosed with cardiac tamponade due to carcinomatous pericarditis. Pulsed Doppler echocardiogram showed prominent isovolumic relaxation flow (IVRF) directed from the cardiac base toward the apex. Such flow is rare in pericardial effusion and may be due to enhanced early diastolic untwisting, sphericalization of apex, and restriction of wall motion by epicardial fibrous tissue. We describe herein a rare case of prominent IVRF with interesting underlying mechanisms. PMID- 27277293 TI - Three-dimensional echocardiographic pictures of isolated double-orifice mitral valve. AB - We present a case of a 12-year-old boy with a rare form of cardiac anomaly, isolated double-orifice mitral valve. He was referred to our hospital at 1.5 years old because of heart murmur. Two-dimensional echocardiography showed double orifice mitral valve without any associated cardiac anomalies. He has been followed carefully without any medication for 11 years. He has had no symptoms and an excellent natural course thus far. PMID- 27277294 TI - Giant left atrial myxoma causing severe pulmonary hypertension. AB - This report describes a case of giant left atrial myxoma in a 43-year-old woman. She presented with general malaise and dyspnea. Electrocardiogram showed severe right-axis deviation. Transthoracic echocardiography demonstrated a giant mobile mass with size of 6.5 * 4.5 cm in the left atrium. This mass protruded into the left ventricle in diastole and disturbed transmitral left ventricular filling flow. Bilateral atrium and right ventricle were dilated. Severe tricuspid regurgitation was demonstrated with peak pressure gradient of 91 mmHg. This mass was surgically excised and was diagnosed as benign atrial myxoma by histological analysis. Pulmonary hypertension was improved after surgery. PMID- 27277295 TI - Visualization of myocardial hemorrhage with real-time three-dimensional myocardial contrast echocardiography in patients with acute myocardial infarction. PMID- 27277296 TI - Cardiac papillary fibroelastoma originated from atrial side of mitral valve leaflet. PMID- 27277297 TI - Bioprosthetic tricuspid valve dysfunction evaluated by real-time three dimensional transesophageal echocardiography. PMID- 27277298 TI - Imaging of pulmonary venous aneurysm. PMID- 27277299 TI - Three-dimensional echocardiography findings of biventricular thrombi complicated by cerebral embolism. PMID- 27277300 TI - Echocardiographic characteristics of aortic intramural hematoma for the differentiation from atheromatous plaques and mural thrombi in the aorta. PMID- 27277301 TI - 41st Annual Meeting - Cape Town, South Africa August 4 - 5, 2016. PMID- 27277302 TI - The effect of high protein diet and exercise on irisin, eNOS, and iNOS expressions in kidney. AB - Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. Irisin, eNOS, and iNOS staining localizations should be supported with various research studies. PMID- 27277303 TI - Functional and pharmacological characterization of two different ASIC1a/2a heteromers reveals their sensitivity to the spider toxin PcTx1. AB - Acid Sensing Ion Channels (ASICs) detect extracellular proton signals and are involved in synaptic transmission and pain sensation. ASIC subunits assemble into homo- and heteromeric channels composed of three subunits. Single molecule imaging revealed that heteromers composed of ASIC1a and ASIC2a, which are widely expressed in the central nervous system, have a flexible 2:1/1:2 stoichiometry. It was hitherto not possible, however, to functionally differentiate these two heteromers. To have a homogenous population of ASIC1a/2a heteromers with either 2:1 or 1:2 stoichiometry, we covalently linked subunits in the desired configuration and characterized their functional properties in Xenopus oocytes. We show that the two heteromers have slightly different proton affinity, with an additional ASIC1a subunit increasing apparent affinity. Moreover, we found that zinc, which potentiates ASIC2a-containing ASICs but not homomeric ASIC1a, potentiates both heteromers. Finally, we show that PcTx1, which binds at subunit subunit interfaces of homomeric ASIC1a, inhibits both heteromers suggesting that ASIC2a can also contribute to a PcTx1 binding site. Using this functional fingerprint, we show that rat cortical neurons predominantly express the ASIC1a/2a heteromer with a 2:1 stoichiometry. Collectively, our results reveal the contribution of individual subunits to the functional properties of ASIC1a/2a heteromers. PMID- 27277320 TI - Clinicopathological features of 11 suspected outbreaks of bovine adenovirus infection and development of a real-time quantitative PCR to detect bovine adenovirus type 10. AB - CASE HISTORY: A retrospective study was conducted to investigate 11 outbreaks of presumptive fatal adenovirus infection diagnosed through two New Zealand diagnostic laboratories during 2014 and 2015. Outbreaks occurred in 6-12-month old Friesian or Friesian cross cattle during autumn, winter and spring. Individual outbreaks were short in duration, with mortality rates ranging from 3/250 to 20/600 (1.2 to 3.3%). CLINICAL AND PATHOLOGICAL FINDINGS: Clinical signs included severe diarrhoea, depression, recumbency, and death. Post-mortem examination revealed congestion and oedema of the alimentary tract and fluid to haemorrhagic intestinal contents. Histopathological lesions were characterised by congestion and haemorrhage of the alimentary tract mucosa, oedema of the submucosa, and mild interstitial inflammation in the kidneys. Large basophilic intranuclear inclusion bodies were identified in vascular endothelial cells of the alimentary tract in 11/11 cases and of the kidney in 8/9 cases. MOLECULAR TESTING: A real-time quantitative PCR (qPCR) assay was designed to detect bovine adenovirus type 10 (BAdV-10) using hexon gene sequences available in GenBank. DNA extracted from a field case and confirmed by sequencing was used as a positive control. The qPCR had a reaction efficiency of 101% (R(2)=0.99) and the limit of detection was <10 DNA copies/reaction. The qPCR detected BAdV-10 in formalin fixed paraffin-embedded (FFPE) tissue from 10/11 cases. DNA sequencing of PCR products from nine of these cases showed them to be identical to BAdV-10 sequences in GenBank. For the PCR-negative case, the PCR product had a hexon sequence 99% similar to bovine adenovirus Wic isolate Ma20-1, a close relative of BadV-10. DIAGNOSIS: Bovine adenovirus type 10 was identified in FFPE tissues from cattle with histopathological evidence of adenovirus infection. CLINICAL RELEVANCE: Bovine adenoviruses, and especially BAdV-10, should be considered in the differential diagnosis for acute enteric disease and death in young cattle. The qPCR detected BAdV-10 from FFPE tissue of cattle with suspected adenoviral infection diagnosed by histopathology. However results should be interpreted in light of clinical and pathological findings due to the possibility of adenovirus shedding by healthy cattle and the presence of pathogenic adenoviruses other than BAdV-10. PMID- 27277319 TI - Copy number variants in the sheep genome detected using multiple approaches. AB - BACKGROUND: Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs. RESULTS: In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %). CONCLUSIONS: This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs. PMID- 27277321 TI - Use of Positron Emission Tomography/Computed Tomography in Radiation Treatment Planning for Lung Cancer. AB - Radiotherapy (RT) plays an important role in the treatment of lung cancer. Accurate diagnosis and staging are crucial in the delivery of RT with curative intent. Target miss can be prevented by accurate determination of tumor contours during RT planning. Currently, tumor contours are determined manually by computed tomography (CT) during RT planning. This method leads to differences in delineation of tumor volume between users. Given the change in RT tools and methods due to rapidly developing technology, it is now more significant to accurately delineate the tumor tissue. F18 fluorodeoxyglucose positron emission tomography/CT (F18 FDG PET/CT) has been established as an accurate method in correctly staging and detecting tumor dissemination in lung cancer. Since it provides both anatomic and biologic information, F18 FDG PET decreases inter-user variability in tumor delineation. For instance, tumor volumes may be decreased as atelectasis and malignant tissue can be more accurately differentiated, as well as better evaluation of benign and malignant lymph nodes given the difference in FDG uptake. Using F18 FDG PET/CT, the radiation dose can be escalated without serious adverse effects in lung cancer. In this study, we evaluated the contribution of F18 FDG PET/CT for RT planning in lung cancer. PMID- 27277322 TI - Morphologic and Metabolic Comparison of Treatment Responsiveness with 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography According to Lung Cancer Type. AB - OBJECTIVE: The aim of the present study was to evaluate the response to treatment by histopathologic type in patients with lung cancer and under follow-up with 18F fluoro-2deoxy-glucose-positron emission tomography/computed tomography (18F-FDG PET/CT) imaging by using Response Evaluation Criteria in Solid Tumors (RECIST) and European Organisation for Research and Treatment of Cancer (EORTC) criteria that evaluate morphologic and metabolic parameters. METHODS: On two separate (pre and post-treatment) 18F-FDG PET/CT images, the longest dimension of primary tumor as well as of secondary lesions were measured and sum of these two measurements was recorded as the total dimension in 40 patients. PET parameters such as standardized uptake value (SUVmax), metabolic volume and total lesion glycolysis (TLG) were also recorded for these target lesions on two separate 18F FDG PET/CT images. The percent (%) change was calculated for all these parameters. Morphologic evaluation was based on RECIST 1.1 and the metabolic evaluation was based on EORTC. RESULTS: When evaluated before and after treatment, in spite of the statistically significant change (p<0.05) in SUVmax, the change was not significant in TLG, in the longest total size and in the longest size (p>0.05). In histopathologic typing, when we compare the post treatment phase change with the treatment responses of RECIST 1.1 and EORTC criteria; for RECIST 1.1 in squamous cell lung cancer group, progression was observed in sixteen patients (57%), stability in seven patients (25%), partial response in five patients (18%); and for EORTC progression was detected in four patients (14%), stability in thirteen patients (47%), partial response in eleven patients (39%), in 12 of these patients an increase in stage (43%), in 4 of them a decrease in stage (14%), and in 12 of them stability in stage (43%) were determined. But in adenocancer patients (n=7), for RECIST 1.1, progression was determined in four patients (57%), stability in two patients (29%), partial response in one patient (14%); for EORTC, progression in one patient (14%), stability in four patients (57%), partial response in two patients (29%) were observed and in these patients, an increase in stage was detected in 3 of them (43%), while 4 of them remained stable. According to histopathologic diagnosis, between squamous cell cancer and adenocancer cases, no significant difference was determined in terms of SUVmax (p>0.05). Post-treatment SUVmax was significantly different in primary tumor but was not significantly different in nodal involvement and metastatic lesions for squamous cell carcinoma patients as compared to the pre-treatment SUVmax measurements. Similarly, there was no significant difference between primary tumor and nodal involvement for adenocarcinoma patients. CONCLUSION: Whether metabolic or morphologic changes are more accurate in evaluating treatment response in lung cancer remains unknown, and there is no gold standard diagnostic method on this issue yet. The most reliable results can only be achieved by survival curve parameters. However, we believe SUVmax seems to provide more easy and practical data for the evaluation of treatment response. PMID- 27277323 TI - Evaluation of Silent Myocardial Ischemia with Single-Photon Emission Computed Tomography/Computed Tomography in Asymptomatic Subjects with Diabetes and Pre Diabetes. AB - OBJECTIVE: The aim of this study was to disclose the prevalence of myocardial ischemia, as detected by adenosine stress myocardial perfusion imaging (MPI) with hybrid single-photon emission computed tomography/computed tomography (SPECT/CT), in asymptomatic diabetic and pre-diabetic patients and to find out whether ischemia predicted the occurrence of adverse cardiac/cerebrovascular events (ACCE) at follow-up. METHODS: Forty-three diabetic and thirty-five pre-diabetic asymptomatic patients without any history of coronary artery disease, underwent MPI and were followed-up for a 12.8+/-2.2 (8-19) months for the occurrence of ACCE. Baseline variables that would predict the presence of ischemia and the value of ischemia on MPI for predicting the occurrence of ACCE at follow-up were evaluated by logistic regression analysis. RESULTS: Ischemia was detected in ten (23.3%) of the diabetic and in four (11.4%) of the pre-diabetic patients. The presence of diabetes was the only independent predictor of myocardial ischemia [odds ratio (OR): 12.31, 95% confidence interval (CI): 1.83-82.66; p<0.01]. During 12.8+/-2.2 (8-19) months of follow-up, ACCE was observed in five out of 78 (6.4%) patients. Patients with ischemia were significantly more likely to have ACCE during follow-up as compared to those with normal MPI scans (event rates: 21.4% vs. 3.1%, OR: 8.455 95% CI: 1.264-56.562, p=0.038). CONCLUSION: Myocardial ischemia as detected by adenosine stress SPECT/CT in a population of asymptomatic patients with diabetes mellitus or pre-diabetes appeared to predict the occurrence of ACCE at follow-up. PMID- 27277324 TI - Is Very High Thyroid Stimulating Hormone Level Required in Differentiated Thyroid Cancer for Ablation Success? AB - OBJECTIVE: Remnant ablation with radioactive iodine (I-131) is a successful form of treatment that aims to destroy the remaining residual tissue and/or metastatic tissue after total thyroidectomy in differentiated thyroid cancer (DTC) patients. High level of thyroid stimulating hormone (TSH) (>=30 mIU/L) is recommended for success of ablation treatment. In this retrospective study, our aim was to investigate whether the TSH levels at the time of ablation effect the success of radioactive iodine remnant ablation. METHODS: Patients who were diagnosed with DTC, treated with bilateral total/near total thyroidectomy and who were referred for I-131 remnant ablation were included in this study. Patients with undetectable TSH-stimulated serum thyroglobulin (Tg) level, normal physical examination, negative results on whole body scan with I-131, and no evidence of neck lymph node metastasis on ultrasound were defined as disease-free. The correlation between TSH level at the time of ablation and ablation success was assessed. RESULTS: Two hundred sixty one consecutive patients were included in the present study. Mean TSH level was 19.47+/-6 mIU/L in the 34 patients with TSH <30 mIU/L, while mean TSH level was 73.65+/-27 mIU/L in the 227 patients with TSH >=30 mIU/L during I-131 remnant ablation. Ablation was unsuccessful in only one patient with TSH <30 mIU/L who had lung metastasis. Ablation was unsuccessful in 5.1% of patients with TSH >=30 mIU/L. The effect of TSH level was not significant on ablation success (p=0.472). CONCLUSION: In conclusion, we think that a high TSH serum level alone is not a factor for the success of ablation. Age, presence of metastasis, extent of residual thyroid mass should also be considered. Especially, in the presence of metastatic tissue, obtaining adequate increase in TSH level is not always possible. The success of ablation at lower levels of TSH elevations may be sufficient for patients, and long-term hypothyroidism may not be required. PMID- 27277325 TI - Recurrence Incidence in Differentiated Thyroid Cancers and the Importance of Diagnostic Iodine-131 Scintigraphy in Clinical Follow-up. AB - OBJECTIVE: Differentiated thyroid cancers (DTC) are tumors with good prognosis. However, local recurrence or distant metastasis can be observed. In our study, we aimed to investigate the incidence of recurrence and the importance of diagnostic iodine-131 whole body scan (WBS) in clinical follow-up in patients with DTC. METHODS: The clinical data of 217 patients with DTC who were followed-up more than 3 years were reviewed retrospectively. The incidence of recurrence was investigated in a group of patients who had radioactive iodine (RAI) treatment and showed no sign of residual thyroid tissue or metastasis with diagnostic WBS that was performed at 6-12 months after therapy and had a thyroglobulin (Tg) level lower than 2 ng/dl. RESULTS: At the time of diagnosis, ten cases had thyroid capsule invasion, 25 cases had extra-thyroid soft tissue invasion, 11 patients showed lymph node metastasis and four patients had distant organ metastasis. One hundred forty-five patients had RAI treatment at ablation dose (75-100 mCi), whereas 35 patients had RAI treatment at metastasis dose (150-200 mCi). Thirty-seven patients with papillary microcarcinoma did not receive RAI treatment. In 12 (%7.5) of the 160 patients who were considered as "successful ablation", a recurrence was identified. Recurrence was detected by diagnostic WBS in all cases and stimulated Tg level was <2 ng/dL with the exception of the two cases who had distant metastasis. CONCLUSION: Identification of pathological findings with WBS in patients who developed local recurrence in the absence of elevated Tg highlights the importance of diagnostic WBS in clinical follow-up. PMID- 27277326 TI - Hypermetabolic Calcified Lymph Nodes on 18Fludeoxyglucose-Positron Emission Tomography/Computed Tomography in a Case of Treated Ovarian Cancer Recurrence: Residual Disease or Benign Formation? AB - The contribution of positron emission tomography/computed tomography (PET/CT) with 18F-fludeoxyglucose (FDG) in evaluating ovarian cancer recurrence even after a prolonged disease-free interval, and in therapy response is well-described. Calcifications observed in CT, although usually attributed to benign conditions, may actually represent active disease. Such an example of calcified formations is psammoma bodies. We present a case of 56-y. o. patient with ovarian cancer relapse at the supraclavicular area 18 years after complete response and disease free interval. The patient received chemotherapy and underwent 18F-FDG-PET/CT for the evaluation of treatment response. Both CT corrected and uncorrected PET images showed hypermetabolism in the massively calcified lymph nodes in the neck, mediastinum, axilla and abdomen, indicative of active residual disease. PMID- 27277327 TI - Sentinel Lymph Node Detection by 3D Freehand Single-Photon Emission Computed Tomography in Early Stage Breast Cancer. AB - We herein present our first experience obtained by 3D freehand single-photon emission computed tomography (SPECT) (F-SPECT) guidance for sentinel lymph node detection (SLND) in two patients with early stage breast cancer. F-SPECT guidance was carried out using one-day protocol in one case and by the two-day protocol in the other one. SLND was performed successfully in both patients. Histopathologic evaluation showed that the excised nodes were tumor negative. Thus, patients underwent breast-conserving surgery alone. PMID- 27277328 TI - Kikuchi Disease with Generalized Lymph Node, Spleen and Subcutaneous Involvement Detected by Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography. AB - Kikuchi-Fujimoto disease, known as Kikuchi disease, is a rare benign and self limiting disorder that typically affects the regional cervical lymph nodes. Generalized lymphadenopathy and extranodal involvement are rare. We report a rare case of a 19-year-old female with a history of persistent fever, nausea, and debilitating malaise. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed multiple hypermetabolic generalized lymph nodes in the cervical, mediastinum, axillary, abdomen and pelvic regions with diffuse spleen, diffuse thyroid gland, and focal parotid involvement, bilaterally. In addition, subcutaneous lesions were noted in the left upper paraspinal and occipital regions. An excisional lymph node biopsy guided by 18F-FDG PET/CT revealed the patient's diagnosis as Kikuchi syndrome. PMID- 27277330 TI - Thermopower measurements in molecular junctions. AB - The measurement of thermopower in molecular junctions offers complementary information to conductance measurements and is becoming essential for the understanding of transport processes at the nanoscale. In this review, we discuss the recent advances in the study of the thermoelectric properties of molecular junctions. After presenting the theoretical background for thermoelectricity at the nanoscale, we review the experimental techniques for measuring the thermopower in these systems and discuss the main results. Finally, we consider the challenges in the application of molecular junctions in viable thermoelectric devices. PMID- 27277329 TI - Daytime nap controls toddlers' nighttime sleep. AB - Previous studies have demonstrated that afternoon naps can have a negative effect on subsequent nighttime sleep in children. These studies have mainly been based on sleep questionnaires completed by parents. To investigate the effect of napping on such aspects of sleep quality, we performed a study in which child activity and sleep levels were recorded using actigraphy. The parents were asked to attach actigraphy units to their child's waist by an adjustable elastic belt and complete a sleep diary for 7 consecutive days. 50 healthy young toddlers of approximately 1.5 years of age were recruited. There was a significant negative correlation between nap duration and both nighttime sleep duration and sleep onset time, suggesting that long nap sleep induces short nighttime sleep duration and late sleep onset time. We also found a significant negative correlation between nap timing and nighttime sleep duration and also a significant positive correlation between nap timing and sleep onset time, suggesting that naps in the late afternoon also lead to short nighttime sleep duration and late sleep onset. Our findings suggest that duration-controlled naps starting early in the afternoon can induce a longer nighttime sleep in full-term infants of approximately 1.5 years of age. PMID- 27277331 TI - The impact of micronized progesterone on the endometrium: a systematic review. AB - Postmenopausal women with an intact uterus using estrogen therapy should receive a progestogen for endometrial protection. International guidelines on menopausal hormone therapy (MHT) do not specify on progestogen type, dosage, route of application and duration of safe use. At the same time, the debate on bioidentical hormones including micronized progesterone increases. Based on a systematic literature review on micronized progesterone for endometrial protection, an international expert panel's recommendations on MHT containing micronized progesterone are as follows: (1) oral micronized progesterone provides endometrial protection if applied sequentially for 12-14 days/month at 200 mg/day for up to 5 years; (2) vaginal micronized progesterone may provide endometrial protection if applied sequentially for at least 10 days/month at 4% (45 mg/day) or every other day at 100 mg/day for up to 3-5 years (off-label use); (3) transdermal micronized progesterone does not provide endometrial protection. PMID- 27277332 TI - Upregulation of microRNA-206 enhances lipopolysaccharide-induced inflammation and release of amyloid-beta by targeting insulin-like growth factor 1 in microglia. AB - Activated microglia are capable of facilitating amyloid-beta (Abeta) accumulation via the release of inflammatory factors, thus resulting in the exacerbation of Alzheimer's disease (AD). MicroRNAs (miRs) participate in the activation of microglia, which is associated with AD. Insulin-like growth factor 1 (IGF1) is a neuroprotective, anti-inflammatory factor, which is able to accelerate clearance of Abeta peptides. The present study aimed to investigate the precise role of miR 206 and IGF1 in lipopolysaccharide (LPS)-induced microglial inflammation. The expression levels of miR-206 and IGF1 were detected in 60 peripheral blood samples from patients with AD and matched age subjects using quantitative polymerase chain reaction. A dual luciferase reporter gene assay was used to indicate the relationship between miR-206 and IGF1. In addition, the role of miR 206 was determined by gain and loss of function experiments in LPS-treated microglia. The results demonstrated that miR-206 upregulation enhanced LPS induced inflammation and Abeta release in microglia by directly targeting the 3' untranslated region of IGF1. These effects were attenuated following treatment with exogenous IGF1, thus indicating that the miR-206/IGF1 signaling pathway may be considered a novel therapeutic target for the treatment of AD-associated microglial inflammation. PMID- 27277333 TI - Low expression of Toll-like receptors in peripheral blood mononuclear cells of pediatric patients with acute lymphoblastic leukemia. AB - Cancer is the second most common cause of death among children aged 1-14 years. Leukemia accounts for one-third of all childhood cancers, 78% of which is acute lymphoblastic leukemia (ALL). The development of cancer has been associated with malignant cells that express low levels of immunogenic molecules, which facilitates their escape from the antineoplastic immune response. It is thought that it may be possible to rescue the antineoplastic immune response through the activation of recognition receptors, such as Toll-like receptors (TLRs), which activate the innate immune system. TLRs are type I membrane glycoproteins expressed mainly in immune system cells such as monocytes, neutrophils, macrophages, dendritic cells, T, B and natural killer cells. The aim of the present study was to evaluate the expression of TLR1, TLR3, TLR4, TLR7 and TLR9 in peripheral blood mononuclear cells (PBMCs) in patients with ALL and prior to any treatment. PBMCs were obtained from 50 pediatric patients diagnosed with ALL and from 20 children attending the ophthalmology and orthopedics services. The mean fluorescence intensity was obtained by analysis of immunofluorescence. We found lower expression levels of TLR1, TLR3, TLR4, TLR7 and TLR9 in PBMCs from patients with ALL compared with those from control patients. We also observed that the PBMCs from patients with Pre-B and B ALL had lower TLR4 expression than controls and patients with Pro-B, Pre-B, B and T ALL had lower TLR7 expression than controls. The present study is the first to demonstrate reduced expression of TLRs in PBMCs from pediatric patients with ALL. This finding is of great relevance and may partly explain the reduction in the antineoplastic immune response in patients with ALL. PMID- 27277334 TI - Pharmacological interventions for clozapine-induced sinus tachycardia. AB - BACKGROUND: Clozapine is an efficacious treatment for treatment-resistant schizophrenia; however its use can be limited by side effect intolerability. Sinus tachycardia is a common adverse event associated with clozapine treatment. Various pharmacological treatments are used to control heart rate increase due to clozapine use and can include a decreased rate of clozapine titration, a switch to a different antipsychotic, or treatment with negative chronotropic drugs. OBJECTIVES: To assess the clinical effects and efficacy of pharmacological interventions for clozapine-induced sinus tachycardia.To systematically review the adverse events associated with pharmacological interventions for clozapine induced sinus tachycardia. SEARCH METHODS: On 23 March 2015, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO and registries of clinical trials. There are no language, date, document type or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: Randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine induced tachycardia. DATA COLLECTION AND ANALYSIS: We independently screened and assessed studies for inclusion using pre-specified inclusion criteria. MAIN RESULTS: The electronic searches located three references. However, we did not identify any studies that met our inclusion criteria. AUTHORS' CONCLUSIONS: With no studies meeting the inclusion criteria, it is not possible to arrive at definitive conclusions. There are currently insufficient data to confidently inform clinical practice. We cannot, therefore, conclude whether specific interventions, such as beta-blockers, are less effective or more effective than standard courses of alternative treatments for tachycardia. This lack of evidence for the treatment of clozapine-induced tachycardia has implications for research and practice. Well-planned, conducted and reported randomised trials are indicated. One trial is currently underway. Current practice outside of well designed randomised trials should be clearly justified. PMID- 27277335 TI - Acute-on-chronic liver failure in cirrhosis. AB - The definition of acute-on-chronic liver failure (ACLF) remains contested. In Europe and North America, the term is generally applied according to the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium guidelines, which defines this condition as a syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure and high short-term mortality. One-third of patients who are hospitalized for acute decompensation present with ACLF at admission or develop the syndrome during hospitalization. ACLF frequently occurs in a closed temporal relationship to a precipitating event, such as bacterial infection or acute alcoholic, drug induced or viral hepatitis. However, no precipitating event can be identified in approximately 40% of patients. The mechanisms of ACLF involve systemic inflammation due to infections, acute liver damage and, in cases without precipitating events, probably intestinal translocation of bacteria or bacterial products. ACLF is graded into three stages (ACLF grades 1-3) on the basis of the number of organ failures, with higher grades associated with increased mortality. Liver and renal failures are the most common organ failures, followed by coagulation, brain, circulatory and respiratory failure. The 28-day mortality rate associated with ACLF is 30%. Depending on the grade, ACLF can be reversed using standard therapy in only 16-51% of patients, leaving a considerable proportion of patients with ACLF that remains steady or progresses. Liver transplantation in selected patients with ACLF grade 2 and ACLF grade 3 increases the 6-month survival from 10% to 80%. PMID- 27277336 TI - Killer-cell immunoglobulin-like receptors and cytomegalovirus reactivation during late pregnancy. AB - Human cytomegalovirus (CMV) represents an important public health concern as it is associated with severe morbidity and mortality in transplant recipients, HIV infected individuals and pregnant women given the risk of congenital infection. Congenital CMV is a leading cause of neurological sequelae, developmental delay and birth defects worldwide. Cytomegalovirus can be transmitted to the foetus following maternal infection or reactivation. NK cells expressing killer-cell immunoglobulin-like receptors (KIR) are part of the innate immune system and the first line of defence against viral incursions. Previous reports have shown that KIR genes are associated with CMV infections in the post-transplant setting. In this study, we set out to determine whether a protective effect of KIR genes over CMV infection is seen in Mexican pregnant women. Cytomegalovirus infection was assessed through nucleic acid testing in 200 pregnant women and 600 healthy blood donors comprising the Mexican mestizo reference population. Killer-cell immunoglobulin-like receptors and HLA-C genotypes were obtained from 200 pregnant women and 300 reference samples using a comprehensive PCR-SSP approach. We observed statistically lower carrier frequencies of cB03|tA01 gene-content haplotype, of cB03 haplotype motif, of the KIR2DL5 + 2DS3/2DS5 gene pair and of KIR2DL5 amongst CMV-positive pregnant women in comparison with those CMV negative. None of these were associated with CMV status in the reference population. Logistic regression analysis revealed that the most important factor determining CMV status during third-trimester pregnancies was the KIR2DL5 + 2DS3/2DS5 gene pair (OR 0.376 (95%CI 0.174, 0.811, P = 0.013). Our results indicate that CMV-protective KIR gene associations described in Caucasoid populations are also present in the genetically distinct Mexican mestizo population. Our results suggest that certain KIR gene combinations provide protection against CMV infections occurring during late-term pregnancies, a finding of utmost epidemiological importance given its implication with congenital CMV infections. PMID- 27277337 TI - Autophagic death induced by thermo-chemotherapy in gastric cancer cells results from the reactive oxygen species pathway. AB - Gastric cancer is the third leading type of cancer and has the third leading cancer-associated mortality in China. The mechanism of thermo-chemotherapy in gastric cancer cells remains to be elucidated. The present study aimed to investigate the role of autophagic cell death in the thermo-chemotherapy of gastric cancer. The current study included four groups: An empty control group, a hyperthermia group, a chemotherapy (oxaliplatin) group, and a thermo-chemotherapy group. Cell viability was analyzed by the MTS assay. Production of intracellular reactive oxygen species (ROS) was quantified by flow cytometry. Autophagy associated proteins, Beclin 1, microtubule-associated protein 1A/1B-light chain (LC3B) and mammalian target of rapamycin (mTOR), were determined by western blot analysis. The results indicated that thermo-chemotherapy markedly increased intracellular ROS production, and decreased mitochondrial membrane potential. The transmission electron microscopy results indicated that thermo-chemotherapy induced production of autophagic bodies. In addition, thermo-chemotherapy-induced cell damage at the cellular and animal levels indicated a notable increase in the expression of the autophagy-associated genes, LC3B and Beclin 1. A negative correlation between mTOR expression and autophagy was also identified, which demonstrates that thermo-chemotherapy induces autophagic cell death by activating the autophagy-associated signaling pathways. The results of the present study demonstrated that the ROS level is important in autophagic death of the gastric carcinoma cells, and the increased ROS level, induced by thermo-chemotherapy treatment, induced autophagy in gastric carcinoma cells. PMID- 27277338 TI - Butyrate-mediated acquisition of chemoresistance by human colon cancer cells. AB - Butyrate is a short-chain fatty acid produced by the intestinal microflora and it not only induces apoptosis but also inhibits the proliferation of cancer cells. Recently, it has been reported that butyrate may cause resistance in colon cancer cells. Therefore, we investigated the effects of increased resistance to butyrate in HCT116 colon cancer cells. We established HCT116 cells resistant to butyrate (HCT116/BR) by treating HCT116 parental cells (HCT116/PT) with increasing concentrations of butyrate to a maximum of 1.6 mM for 3 months. The butyrate concentrations that inhibited cell growth by 50% (IC50) were 0.508 and 5.50 mM in HCT116/PT and HCT116/BR cells. The values after treatment with paclitaxel, 5 fluorouracil (5-FU), doxorubicin and trichostatin A (TSA) were 2.42, 2.36, 4.31 and 11.3-fold higher, respectively, in HCT116/BR cells compared with HCT116/PT cells. The protein expression of drug efflux pumps, such as P-glycoprotein (P gp), breast cancer-resistant protein (BCRP) and the multidrug resistance associated protein 1 (MRP1), did not differ between HCT116/PT and HCT116/BR cells. The expression level of the anti-apoptotic Bcl-xL protein was increased while those of pro-apoptotic Bax and Bim proteins were reduced in HCT116/BR cells. There were no significant differences in cell motility and invasion. This study suggests that exposure of colon cancer cells to butyrate results in development of resistance to butyrate, which may play a role in the acquisition of chemoresistance in colon cancer. PMID- 27277339 TI - Structure dependence of lasing action in organic polymer films on DFB gratings for dinitrotoluene vapor detection. AB - Structure effects of distributed feedback (DFB) gratings on lasing action have been investigated for detecting explosive vapors. For the first time, we have established the optimized profiles of the DFB grating, and given the theoretical path to design its structure for amplified spontaneous emission (ASE) of organic polymer films based on Bragg conditions. A poly(p-phenylene ethynylene) (PPE) film can realize detection of dinitrotoluene (DNT) vapors in 2 min with a reduced excitation threshold of 26 mJ cm(-2) by using a simple and common 405 nm laser. PMID- 27277340 TI - VEGF in nuclear medicine: Clinical application in cancer and future perspectives (Review). AB - Clinical trials using antiangiogenic drugs revealed their potential against cancer. Unfortunately, a large percentage of patients does not yet benefit from this therapeutic approach highlighting the need of diagnostic tools to non invasively evaluate and monitor response to therapy. It would also allow to predict which kind of patient will likely benefit of antiangiogenic therapy. Reasons for treatment failure might be due to a low expression of the drug targets or prevalence of other pathways. Molecular imaging has been therefore explored as a diagnostic technique of choice. Since the vascular endothelial growth factor (VEGF/VEGFR) pathway is the main responsible of tumor angiogenesis, several new drugs targeting either the soluble ligand or its receptor to inhibit signaling leading to tumor regression could be involved. Up today, it is difficult to determine VEGF or VEGFR local levels and their non-invasive measurement in tumors might give insight into the available target for VEGF/VEGFR dependent antiangiogenic therapies, allowing therapy decision making and monitoring of response. PMID- 27277341 TI - Effect of limestone particle size and calcium to non-phytate phosphorus ratio on true ileal calcium digestibility of limestone for broiler chickens. AB - The purpose of this study was to determine the effect of limestone particle size and calcium (Ca) to non-phytate phosphorus (P) ratio on the true ileal Ca digestibility of limestone for broiler chickens. A limestone sample was passed through a set of sieves and separated into fine (<0.5 mm) and coarse (1-2 mm) particles. The analysed Ca concentration of both particle sizes was similar (420 g/kg). Six experimental diets were developed using each particle size with Ca:non phytate P ratios of 1.5:1, 2.0:1 and 2.5:1, with ratios being adjusted by manipulating the dietary Ca concentrations. A Ca-free diet was also developed to determine the basal ileal endogenous Ca losses. Titanium dioxide (3 g/kg) was incorporated in all diets as an indigestible marker. Each experimental diet was randomly allotted to 6 replicate cages (8 birds per cage) and fed from d 21 to 24 post hatch. Apparent ileal digestibility of Ca was calculated using the indicator method and corrected for basal endogenous losses to determine the true Ca digestibility. The basal ileal endogenous Ca losses were determined to be 127 mg/kg of dry matter intake. Increasing Ca:non-phytate P ratios reduced the true Ca digestibility of limestone. The true Ca digestibility coefficients of limestone with Ca:non-phytate P ratios of 1.5, 2.0 and 2.5 were 0.65, 0.57 and 0.49, respectively. Particle size of limestone had a marked effect on the Ca digestibility, with the digestibility being higher in coarse particles (0.71 vs. 0.43). PMID- 27277342 TI - In vitro characterization of TMPRSS2 inhibition in IPEC-J2 cells. AB - The transmembrane serine protease, TMPRSS2 is an important target in the treatment of seasonal influenza infections and contributes to prostate carcinogenesis and metastasis. In this study, the effect of the synthetic TMPRSS2 inhibitor I-432 on jejunal IPEC-J2 cell monolayers cultured on membrane inserts was characterized. Using a fluorogenic substrate, it was found that the apical addition of I-432 could suppress trypsin-like activity in the supernatants of IPEC-J2 cells. The inhibition of TMPRSS2 did not affect physiologically produced hydrogen peroxide levels in the apical and in basolateral compartments. Loss of expression of the TMPRSS2 serine protease domain (28 kDa) was also observed when cells were pre-exposed to I-432. Partial decrease in immunofluorescent signal intensities derived from the altered distribution pattern of TMPRSS2 was detected after a 48 h long incubation of IPEC-J2 cells with the inhibitor indicating the efficacy of TMPRSS2 inhibition via I-432 administration in vitro. PMID- 27277345 TI - A stable room-temperature sodium-sulfur battery. AB - High-energy rechargeable batteries based on earth-abundant materials are important for mobile and stationary storage technologies. Rechargeable sodium sulfur batteries able to operate stably at room temperature are among the most sought-after platforms because such cells take advantage of a two-electron-redox process to achieve high storage capacity from inexpensive electrode materials. Here we report a room-temperature sodium-sulfur battery that uses a microporous carbon-sulfur composite cathode, and a liquid carbonate electrolyte containing the ionic liquid 1-methyl-3-propylimidazolium-chlorate tethered to SiO2 nanoparticles. We show that these cells can cycle stably at a rate of 0.5 C (1 C=1675, mAh g(-1)) with 600 mAh g(-1) reversible capacity and nearly 100% Coulombic efficiency. By means of spectroscopic and electrochemical analysis, we find that the particles form a sodium-ion conductive film on the anode, which stabilizes deposition of sodium. We also find that sulfur remains interred in the carbon pores and undergo solid-state electrochemical reactions with sodium ions. PMID- 27277346 TI - Correlation between Umbilical Cord Diameter and Cross Sectional Area with Gestational Age and Foetal Anthropometric Parameters. AB - The objective of the study was to find out correlation between umbilical cord diameter, cross sectional area with gestational age and foetal anthropometric parameters. This cross sectional study was conducted among healthy women between the 24(th) and 40(th) completed weeks of a normal pregnancy in the Department of Radiology & Imaging, Mymensingh Medical College Hospital, Mymensingh during the study period, from July 2009 to June 2011. A total of 230 consecutive normal pregnancy patients were included in the study. The diameter & cross-sectional area of the umbilical cord were measured on a plane adjacent to the junction of the umbilical cord and the fetal abdomen, in cross-section, with maximum magnification of the image. The cord was manually circled, and it's cross sectional areas was automatically calculated by the ultrasonograph. The mean+/-SD age was 24.3+/-4.7 years with range from 19 to 36 years. The mean gestational age was 32.1+/-4.5 weeks and more than a half (56.4%) of the pregnant women were nulliparas. A positive significant (p<0.001) correlation were found between umbilical cord diameter with bi-parietal diameter (r=0.548); head circumference (r=0.411); abdominal circumference (r=0.444); femur length (r=0.366) and gestational age gestation age (r=0.643). Similarly, a significant (p<0.001) positive week correlation were found between umbilical cross sectional area with bi-parietal diameter (r=0.3303); head circumference (r=0.3202); abdominal circumference (r=0.2651); femur length (r=0.3307) and gestation age (r=0.4051). A positive significant better correlation was found with umbilical cord diameter than cross sectional area with foetal anthropometric parameters. PMID- 27277343 TI - Rapid diagnosis of lymph node metastasis in breast cancer using a new fluorescent method with gamma-glutamyl hydroxymethyl rhodamine green. AB - Sentinel lymph node biopsy is performed as a standard procedure in breast cancer surgery, and the development of quick and simple methods to detect metastatic lesions is in high demand. Here, we validated a new fluorescent method using gamma-glutamyl hydroxymethyl rhodamine green to diagnose metastatic lymph nodes in breast cancer. One hundred and forty-nine lymph nodes from 38 breast cancer patients were evaluated in this study. Comparison of fluorescent and pathological images showed that this fluorescent method was successful for visualizing breast cancer cells in lymph nodes. This method had a sufficiently high sensitivity (97%), specificity (79%) and negative predictive value (99%) to render it useful for an intraoperative diagnosis of cancer. These preliminary findings suggest that this novel method is useful for distinguishing non-cancerous specimens from those in need of careful examination and could help save time and cost for surgeons and pathologists. PMID- 27277344 TI - Strong preference of BRCA1 protein to topologically constrained non-B DNA structures. AB - BACKGROUND: The breast and ovarian cancer susceptibility gene BRCA1 encodes a multifunctional tumor suppressor protein BRCA1, which is involved in regulating cellular processes such as cell cycle, transcription, DNA repair, DNA damage response and chromatin remodeling. BRCA1 protein, located primarily in cell nuclei, interacts with multiple proteins and various DNA targets. It has been demonstrated that BRCA1 protein binds to damaged DNA and plays a role in the transcriptional regulation of downstream target genes. As a key protein in the repair of DNA double-strand breaks, the BRCA1-DNA binding properties, however, have not been reported in detail. RESULTS: In this study, we provided detailed analyses of BRCA1 protein (DNA-binding domain, amino acid residues 444-1057) binding to topologically constrained non-B DNA structures (e.g. cruciform, triplex and quadruplex). Using electrophoretic retardation assay, atomic force microscopy and DNA binding competition assay, we showed the greatest preference of the BRCA1 DNA-binding domain to cruciform structure, followed by DNA quadruplex, with the weakest affinity to double stranded B-DNA and single stranded DNA. While preference of the BRCA1 protein to cruciform structures has been reported previously, our observations demonstrated for the first time a preferential binding of the BRCA1 protein also to triplex and quadruplex DNAs, including its visualization by atomic force microscopy. CONCLUSIONS: Our discovery highlights a direct BRCA1 protein interaction with DNA. When compared to double stranded DNA, such a strong preference of the BRCA1 protein to cruciform and quadruplex structures suggests its importance in biology and may thus shed insight into the role of these interactions in cell regulation and maintenance. PMID- 27277347 TI - Comparative Study between Pentoxifylline and Pioglitazone in the Treatment of Non Alcoholic Fatty Liver Disease among Newly Detected Glucose Intolerant Patients. AB - This quasi experimental study was carried out to compare the efficacy of Pentoxifylline versus Pioglitazone in non-alcoholic fatty liver disease (NAFLD) among newly detected glucose intolerant patients attended at GHPD, BIRDEM, Dhaka, Bangladesh from March 2011 to May 2012. Sixty patients with newly detected abnormal glucose tolerance, naive to any antidiabetic drugs were randomly selected, with the findings of USG changes of fatty liver and raised ALT. Patients were divided into Group A (51.7%; mean age - 44.45+/-7.34 years, BMI - 26.76+/-3.65kg/m(2)) receiving Pioglitazone 30mg/day and Group B (48.3%; mean age - 43.97+/-10.13 years, BMI - 27.52+/-4.44kg/m(2)) receiving Pentoxifylline 1200mg/day along with dietary and lifestyle modification. Baseline, follow up 1 & follow up 2: Serum AST in Group A (66.58+/-40.78U/L, 45.00+/-19.43U/L and 33.25+/ 9.92U/L) respectively and in Group B (54.13+/-20.11U/L, 38.31+/-12.90U/L and 30.62+/-9.63U/L) respectively. Serum ALT in Group A (113.48+/-61.38U/L, 61.16+/ 19.45U/L and 42.45+/-13.84U/L) respectively & in Group B (99.13+/-37.95U/L, 50.27+/-15.95U/L and 37.24+/-9.51U/L) respectively. No patient with normal USG finding was included in the study. Baseline USG finding: Grade I - Group A (35.5%), Group B (27.6%); Grade II - Group A (54.8%), Group B (48.3%); Grade III Group A (9.7%), Group B (24.1%). Final Follow up: Normal - Group A (16.1%), Group B (10.3%); Grade I - Group A (38.7%), Group B (34.5%); Grade II - Group A (41.9%), Group B (44.8%); Grade III - Group A (3.2%), Group B (10.3%). Within groups findings were statistically significant (P<0.001) but between groups not significant (P>0.001). Biochemical and USG grading were improved in follow ups in both the groups. Such findings were observed due to synergistic effect of both therapeutic intervention along with supplementary dietary and lifestyle modification. Both Pioglitazone and Pentoxifylline have similar therapeutic outcome combined with supplementary dietary and lifestyle modification. PMID- 27277348 TI - Estimation of Thyroid Hormone in Early Pregnancy and it's Clinical Correlation. AB - This descriptive cross sectional study was done for the estimation of thyroid hormone in early pregnancy and it's clinical correlation. It was conducted at the Antenatal Clinic of Mymensingh Medical College Hospital, Mymensingh from December 2010 to November 2011. Total 185 cases in early pregnancy were taken purposively and randomly. Among the pregnant women, age ranged from 18-42 years with the Mean+/-SD age 25.77+/-4.96 years, the gestational weeks ranged 6+/-1 to 13+/ 1weeks having Mean+/-SD 9.06+/- 2.49 weeks. The gravida ranged from primi to 8th gravida Mean+/-SD 1.89+/-1.10. Haemoglobin level ranged from 9.0 to 13.2gm/dl; Mean+/-SD 10.90+/-0.99gm/dl. Mean+/-SD of serum FT4 was 17.77+/-7.25 and Mean+/ SD of TSH was 3.95+/-2.94mIU/L. In present study, 5.40% (n=10) of the respondents had hypothyroidism and 0.54% (n=1) showed hyperthyroidism. The present study showed that, the incidence of hypothyroidism had relatively increased then the reference ranges but not statistically significant. But hyperthyroidism was within the reference range. This study showed slightly higher percentage of hypothyroidism in both <=30 (4.52%) and >=30 (10%) years of age groups especially a bit higher percentage in the elderly group. In present study, hypothyroidism was common among women of lower income group. Present study showed a higher percentage of stillbirth &miscarriage among study population. This study showed a relatively higher prevalence of abnormal thyroid function (especially hypothyroidism) in the study population and suggests the routine screening of thyroid hormone in early pregnancy in addition to routine antenatal care. PMID- 27277349 TI - Serum Glucose Level in First and Third Trimester of Pregnancy. AB - In the present study serum glucose were estimated in pregnant women during the first trimester of pregnancy and third trimester of pregnancy to observe the frequency of hyperglycemia during pregnancy and to assess the incidence of gestational diabetes mellitus. This study was a cross sectional study, carried out in the Department of Physiology of Mymensingh Medical College, Mymensingh from July 2014 to June 2015. For this purpose, total 300 women with age ranged from 18 to 35 years were selected and divided into 100 healthy non pregnant women as control group and 200 normal pregnant women as study group. Study group was further divided into 100 pregnant women in first trimester of pregnancy and 100 pregnant women in third trimester of pregnancy. Diagnosed case of type I and type II diabetes, hypothyroidism, cushing's syndrome, polycystic ovary, antipsychotic drug users, regular steroid users were excluded from this study. Serum glucose was evaluated by the glucose-oxidase principle by GOD-PAP method in women with 1st trimester of pregnancy, 3rd trimester of pregnancy and in non pregnant women. Statistical analysis of data was done by unpaired student's t test. The results showed that the serum glucose levels increased significantly in third trimester and the value is not significant in first trimester. The increasing frequency of serum glucose level in third trimester may predispose the women to hyperglycemia of pregnancy or gestational diabetes mellitus. PMID- 27277351 TI - Comparison between Angiographic Findings of Coronary Artery Disease in STEMI and NSTEMI Patients of Bangladesh. AB - Coronary Angiogram (CAG) has been used to detect coronary artery disease in myocardial infarction (both STEMI and NSTEMI) patients. The purpose of this study was to compare the degree of coronary artery disease among STEMI and NSTEMI patients. Among acute coronary syndrome in NSTEMI we found more widespread coronary artery disease other than STEMI. Lack of documentations encouraged us to perform this study in our center. In this retrospective observational study we summarized all myocardial infarction (MI) patients who underwent coronary angiography (CAG) from August 2013 to August 2014 at Enam Medical College Hospital, Dhaka, Bangladesh and data of degree of coronary artery disease were recorded. Data of 100 consecutive MI patients who underwent CAG during that period were recorded. Among them 50 patients having STEMI as Group I (male 45, female 5) & other 50 patients sustained NSTEMI as Group II (male 38, female 12). Among NSTEMI patient group 80% were having multi-vessel disease and in STEMI patient group 80% having single vessel disease and remaining having multi-vessel disease. The degree of coronary artery disease is extensive in NSTEMI patients than in STEMI group. Coronary angiogram can visualize the degree of coronary artery involvement and is a useful screening modality to compare disease extent in MI patients. PMID- 27277350 TI - Serum Uric Acid Level among Acute Stroke Patients. AB - Stroke is one of the leading causes of death and disability in developed as well as developing countries like Bangladesh. Elevated serum uric acid levels may predict an increased risk for cerebro-vascular (CV) events including stroke. Aim of the study was to measure the serum uric acid level among stroke patients and determine the relationship between serum uric acid level and stroke. This descriptive, cross-sectional study was carried out in Department of Medicine, Mymensingh Medical College Hospital, Mymensingh, Bangladesh to measure serum uric acid level among 102 stroke patients in a period of one year by using non probability sampling procedure. Finally, collected data were analyzed using SPSS software Version 17.0. It was observed that the mean age of patients was 60.87+/ 8.05 years, of them 80(78.43%) patients were male and the rest 22(21.57%) were female. About 66(64.70%) of respondents were in age group 60 years and above, while 36(35.30%) were in age group 59 years and below. At least 23(22.55%) of stroke patients had elevated serum uric acid with a mean serum uric acid level of 5.18mg/dl and standard deviation 1.26mg/dl. About 23(27.38%) patients in ischemic stroke had elevated serum uric acid whereas 18(100%) patients in hemorrhagic stroke had normal uric acid level. Uric acid level was elevated in ischemic stroke than haemorrhagic stroke patients (p<0.001). High uric acid level may be considered as a risk factor in patients with acute ischemic stroke. PMID- 27277353 TI - Histomorphological Study on Number of Acini of the Prostate Gland of Bangladeshi Cadaver. AB - The prostate is made up of 30 to 50 compound tubuloalveolar glands that are embedded in a framework of fibromuscular tissue and arranged in three concentric groups (mucosal, submucosal and main prostatic gland). The prostate consists of peripheral, central and transitional zone accounting for approximately 70%, 20% and 5% of the glandular substances. Benign prostatic hyperplasia affects the transitional zone and carcinoma of the prostate affects the peripheral zone. The glandular tissue consists of numerous acini with frequent internal papillae. Follicular epithelium is variable but predominantly columnar and either single layered or pseudostratified. This cross sectional descriptive study was conducted in Department of Anatomy, Mymensingh Medical College, Mymensingh, Bangladesh to find out the difference in number of acini of the prostate gland of Bangladeshi people in relation to age. The present study was performed on 67 postmortem human prostate gland collected from the morgue in the Department of Forensic Medicine, Mymensingh Medical College by non random purposive sampling technique. The specimens were collected from Bangladeshi cadaver of age ranging from 10 to 80 years. All the specimens were grouped into three categories: Group A (up to 18 years), Group B (19 to 45 years) and Group C (above 45 years) according to age. Dissection was performed following standard autopsy techniques. In the present study, total 60 slides were made for histological study from both central and peripheral zone of the prostate which were examined under low power objectives. The number of the acini of the prostate gland were counted and recorded. The mean number of the acini of the prostate gland was 16.45, 43.54 and 42.45 in Group A, B and C respectively in central zone and 30.08, 51.35 and 44.16 in Group A, B and C respectively in peripheral zone of the prostate. Variance analysis shows that mean differences were highly significant between Group A & B and Group C & A and non significant between Group B & C in central zone of the prostate. Mean differences were non significant among all three groups in peripheral zone of the prostate. The number of the acini of prostate gland was increased up to certain age limit but decreased in extreme age. In statistical analysis, differences between age groups were analyzed by using students unpaired 't' test. The present study will help to increase the information pool on the number of the acini of the prostate gland of Bangladeshi people at different age group. PMID- 27277352 TI - Correlation between Troponin-I and B-Type Natriuretic Peptide Level in Acute Myocardial Infarction Patients with Heart Failure. AB - Troponins are regarded as markers of choice for the diagnosis of acute myocardial infarction (AMI). But B-type natriuretic peptide (BNP) level is also elevated in AMI and is a quantitative biochemical marker related to the extent of infarction and the left ventricle systolic dysfunction. Thus, BNP has prognostic value. In this study, we investigate the correlation of Troponin-I with BNP levels in patients presenting with AMI with or without Acute Heart Failure. Rationale of this study is to see, whether quantitative Troponin alone can serve for both diagnosis and prognosis of AMI Patients with heart failure or not. This cross sectional analytical study was conducted in the Department of Cardiology in Mymensingh Medical College Hospital from January 2014 to December 2014. Total 100 patients were studied and divided into two groups - 50 patients in each group. Group I: Patients with first attack of acute myocardial infarction (without heart failure) & Group II: Patients with first attack of acute myocardial infarction with acute heart failure. Mean Troponin-I of Group I and Group II were 3.10+/ 2.68 and 62.93+/-32.75ng/ml respectively & mean BNP value of Group I and Group II were 20.96+/-14.18 and 615.65+/-249.27pg/ml respectively. In this study, it was shown that the levels of BNP had positive correlation with Troponin-I levels, with medium strength of association (r=0.734, p<0.05). Echocardiography shows that patients with high BNP level has low ejection fraction (LVEF) and patients with low BNP level has preserved ejection fraction (LVEF). Thus, the present study shows that the higher the Troponin-I levels, the higher the BNP levels in first attack of AMI patients and the more severe the heart failure (more severe left ventricle dysfunction). There is positive correlation between Troponin-I and BNP levels in first attack of AMI patients with acute heart failure. PMID- 27277354 TI - Associations and Risk Factors of Diabetic Maculopathy. AB - Diabetic maculopathy is characterised by increased capillary leakage in the main retinal vessels and by alterations in the microcirculation of the macula. Maculopathy occurs frequently in type 1 and type 2 diabetic patients. Prevalence is higher in type 2 than in type 1 diabetic patients. Factors associated with the development of maculopathy are mostly unknown. As maculopathy is the main cause of vision deprivation in diabetic patients it is essential to know the associations and risk factors of diabetic maculopathy so that appropriate measures can be taken to prevent as well as treat diabetic maculopathy. We started the research work to find out the relation between diabetic maculopathy and various associated factors and risk factors for patients with diabetic retinopathy with maculopathy. This cross-sectional observational study done at the Department of Ophthalmology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka & National Institute of Ophthalmology & Hospital (NIO & H), Sher-e Bangla Nagar, Dhaka, Bangladesh from January 2006 to June 2006. In this study out of 50 patients, diabetes was controlled in 20(40%) patients and uncontrolled in 30(60%). A significant percentage of patients (40%) had elevated blood pressure. Diabetic autonomic neuropathy was observed in 24% cases and polyneuropathy was observed in 36% cases. It is evident that diabetic maculopathy has association with dyslipidaemia, abnormal renal function due to nephropathy. This study lighted on the association of diabetic maculopathy with diabetic nephropathy, cardiac abnormalities and diabetic neuropathy. PMID- 27277355 TI - A Survey on Current Practice of Management of Early Onset Neonatal Sepsis. AB - It was a survey type of cross sectional study where the participants were from different teaching/referral hospital across the country and was done to gather information regarding current practice of management of neonatal sepsis among paediatricians and neonatologists and was conducted on the spot during a national conference of Bangladesh Perinatal Society in December 2013. Specialists in neonatology, paediatrics, and some other disciplines working in different institutes across the country were requested to respond. Out of 150 physicians, 92 (61.33%) were neonatologists. Physicians suspected early onset neonatal sepsis (EONS) when there is history suggestive of prolonged rupture of membrane (74.77%), prolonged labour (9.33%), chorioamnionitis (7.33%) and maternal fever (2%). Clinical sepsis is found commonly (53.33%) which is later proved by laboratory evidences such as Hb%, TC, DC PBF (peripheral blood film), C-reactive protein, chest X-ray etc. Injection Ampicillin and Gentamycin are still the first choice of antibiotics (61.3%). Preferred route was intravenous (95.3%). Antibiotics were given for 7-10 days by most of the physicians (48.77%). However there is lack of uniformity among the participants in regard to taking decision about antibiotics, the choice of first line and the subsequent options of antibiotics. So, neonatal sepsis is the most important cause of neonatal mortality in the community. Therefore a standard protocolized approach for diagnosis and management of Early Onset Neonatal Sepsis may prove critical which is currently not in practice uniformly. PMID- 27277356 TI - Challenges in HbA1c Analysis and Reporting in Patients with Variant Hemoglobins. AB - Hemoglobin A1c (HbA(1)c) is a well-established indicator of mean glycemia. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA(1)c measurements. Variants of hemoglobin especially Hemoglobin E (HbE) is prevalent in South East Asia including Bangladesh. The objective of our study is to compare the HbA(1)c values measured on high performance liquid chromatography (HPLC) and Turbidimetric Inhibition Immunoassay (TINIA) in diabetic patients with variant hemoglobins including HbE. A total of 7595 diabetic patients receiving treatment at BIRDEM General Hospital were analyzed for HbA(1)c results within a period of two months from December 2013 to January 2014. Seventy two cases out of 7595 (0.95%) had either undetectable or below normal HbA(1)c levels (males-33 and females-39; ratio = 0.82:1) by HPLC method. In 34(0.45%) cases, HbA(1)c value was undetectable by HPLC method but was in the reportable range by TINIA method. In the other 38 (0.55%) cases, HbA(1)c levels were below the reportable range (<4%) by HPLC method but were in the normal or higher range by TINIA method. TINIA method did not agree with HPLC method on Bland Altman plot in the 38 cases with below normal HbA(1)c levels, [Mean bias -5.2(-9.3 to 1.0), 95% CI] but agreed very well [mean bias -0.21 (-0.84 to 0.42), y=1.1037+0.776X; r(2)=0.30, p<0.01] in controls. In control group mean MCV was 83.80+/-7.48 and in study group was 73.65+/-10.44. Alkaline electrophoresis confirmed the variant hemoglobin to be HbE. The fasting blood sugar levels of all the 72 cases correlated strongly with TINIA method (r(2) =0.75, p<0.0001) but not with HPLC (r = 0.24, p=0.13). In our regions where populations have a high prevalence of Hb variant, proper knowledge of hemoglobin variants which affect the measurements HbA(1)c level is essential. MCV of 80fl or below may serve as a rough guide to select samples that require analysis by TINIA method. Moreover, HPLC may be a convenient and inexpensive tool for screening of hemoglobinopathies especially among diabetic population in Bangladesh. It may therefore be helpful in improving management of complications related to both anaemia and iron overload. PMID- 27277357 TI - Effect of Serum Lipoprotein (a) [Lp(a)] in Menopausal Women. AB - The behavior of LP during the menopausal trinities and their relationship with sex hormones and body fat distribution is still unclear. The aim of this case control study was to estimate the serum lipoprotein (a) in postmenopausal women and women in reproductive age group and comparison of the above mention serum lipids between the two groups and was carried out in the Department of Biochemistry, Dhaka Medical College (DMC), Dhaka, in co-operation with the Department of Immunology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka from July-2005 to June 2006. A total number of 70 women were selected. Selected women were grouped as Group A and Group B. In Group A 30 postmenopausal women were selected with age range 55-70 years. In Group B, 40 women within reproductive age were selected. Group B was again divided into two groups - Group B1 & Group B2 according to their ages. In Group B1 20 women were selected with age range 25-35 years, and in Group B2 another 20 women were selected with age range 36-45 years. Serum lipoprotein (a) or Lp(a) and lipid profile of all groups were measured. Mean sLp(a) concentration were compared between groups by" Mann Whitney U" test. Mean concentrations of every individual components of lipid profile (sTAG, sTc, sLDL & sHDL) were compared with different groups. sLp(a) concentration of Group A compared to Group B1 was found to be significantly higher (p<0.001). In the same way mean serum Lp(a) concentration of Group A compared to Group B2 was also significantly higher (p<0.001). Mean sLp(a) concentration of B1 compared B2 did not differ significantly. Mean values of lipid profiles were slightly elevated in Group A compared to Group B1 and Group B2 except sHDL-c level. Mean concentrations HDL-c was significantly lower in Group A compared to Group B1 and Group B2. Thus the present study has revealed that there is increased Lp(a) in menopause & decreased HDL in menopause. PMID- 27277358 TI - Outcome of Endoscopic Sinus Surgery in the Treatment of Chronic Rhinosinusitis. AB - This prospective study was conducted to compare the outcome of endoscopic sinus surgery (ESS) using SNOT-20 score chart (subjective) and Lund & Kennedy scoring chart (objective) and carried out in the Department of Otolaryngology & Head-Neck Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Dhaka Medical College Hospital (DMCH) & Shaheed Suhrawardy Medical College Hospital (ShSMCH) from July 2010 to March 2012. Total 73 admitted cases were selected purposively for ESS, male 53(72.60%) and female 20(27.40%). Among the study participants 10(13.7%) had chronic rhinosinusitis with bilateral polyposis and 26(35.62%) had chronic rhinosinusitis with unilateral polyposis and 12(16.44%) had bilateral chronic rhinosinusitis without polyposis and 25(34.25%) had unilateral chronic rhinosinusitis without polyposis. Surgical procedures done among the patients were Uncinectomy (infundibulectomy), Middle Meatal Antrostomy; Anterior Ethmoidectomy; Sphenoidotomy, Associated septoplasty and no significant per or post operative complications were noted. In Chronic rhinosinusitis (CRS) with polyposis pre operative SNOT-20 mean and SD 1.322+/-0.341 and post ESS snot 20 mean and SD 0.3472+/-0.0755, CRS without polyposis pre operative SNOT-20 mean and SD 0.9297+/-0.86 and post ESS SNOT-20 mean and SD 1986+/-0.0558. In CRS with polyposis pre operative Lund & Kennedy score of endoscopic assessment, mean and SD 5.333+/-2.255 and post ESS mean and SD 1.31+/-1.009. In CRS without polyposis pre op Lund & Kennedy score mean and SD 3.108+/-1.074 and post ESS mean and SD 0.76+/-0.641.Post ESS SNOT-20 in CRS with Polyposis, 't' test result was 27.58 which was significant (p<0.001) and in CRS without Polyposis was 21.622 which was significant (p<0.001); Lund & Kennedy Score of post ESS in CRS with Polyposis 't' test result was 7.763 which was significant (p<0.001), CRS without Polyposis was 7.177 which was significant (p<0.001).This implies that outcome of ESS in treatment of CRS with or without polyposis had statistically significant role. Symptomatic relief and quality of life improvement after ESS was compared by improvement in post operative scores of SNOT-20 & Lund-Kennedy score of endoscopic assessment. Post operative lower values were considered to be better improvement status. The results of the study suggests that ESS performed in Chronic Rhinosinusitis without Polyposis cases, relief of symptoms and quality of life improved was better than Chronic Rhinosinusitis with Polyposis cases postoperatively as compared by SNOT-20 and Lund & Kennedy score of endoscopic assessment. PMID- 27277359 TI - CRP (C-reactive protein) in Early Pregnancy Predictor for Development of GDM. AB - This case-control study was done to find out whether elevated serum CRP in early pregnancy is a predictor of GDM and conducted under joined supervision of Obstetrics & Gynecology Department, Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital and Biomedical Research Group (BMRG), BIRDEM, from August 2005 to November 2007. Pregnant mothers at their first 16 weeks of gestation without any medical disorder of pregnancy were included in the study. For the purpose of this study blood samples were again collected for OGTT at their 16weeks, 24-28 weeks and 32 weeks of pregnancy to detect GDM. After confirmation of GDM, C reactive protein and C-peptide were done from the preserved fasting serum sample at the end of this study to compare GDM with control group. A total of 297 patients were included in this study. Among them 145(48%) patients completed follow up, 59(20%) lost from follow-up and 11(4%) patients had abortion; 82(28%) are due for follow up 31(10%) pregnant patients developed GDM subsequently. Finally 28 GDM patients were taken as cases and 71 were control matched for their gestational age and parity. At earlier weeks of gestation, hsCRP could predict (PPV) development of GDM in 59% with NPV 84%, sensitivity 61% and specificity 83%. C-peptide in the 50th percentile could predict (PPV) development of GDM in 58% with NPV 96%, sensitivity 72% and specificity 93%. The present data indicates that hsCRP and C-peptide both is sensitive markers in predicting GDM. PMID- 27277360 TI - Preoperative Assessment of Serum Albumin Level as Risk Factor for Morbidity Following Routine Oncological Surgery. AB - This cross-sectional observational study was to establish the preoperative assessment of serum albumin level as indicator for morbidity following cancer surgery and to reduce the incidence of related postoperative complications. Therefore this study was undertaken to assess the morbidity associated with low serum level albumin and identify it as a risk factor following cancer surgery in Bangladeshi population. This study included 312 patients with malignancy who were waiting for surgery or within 60 days of postoperative period were enrolled for the study from indoor of surgical oncology department, National Institute of Cancer Research & Hospital (NICR&H), Dhaka, Bangladesh. Then the patients were submitted for further study to evaluate the preoperative fitness in terms of nutritional assessment - both clinical and biological especially serum albumin level. All the clinical (pre & post-operative including complication, if any), investigation findings were recorded accordingly. Statistical correlation was discovered between BMI and morbidity but no statistical correlation was found between WL >10% and major surgical complications of either infectious or noninfectious origin (p=NS). Conversely, a substantial statistical correlation was found between Hb% or albumin <30gm/l and major surgical complications (either infectious or noninfectious) (p<0.001). The serum albumin level below 30gm/l is a significant risk factor for oncological postoperative major complications (MC). PMID- 27277361 TI - Mini-Laparoscopic Cholecystectomy: Review of 7200 Cases. Could it be the New Gold Standard? AB - Mini-Laparoscopy by reducing the instrument size and hence incision can lead to better surgical outcome. The safety and feasibility of mini-laparoscopic cholecystectomy (mini-Lch) has not been documented with a large patient sample. This observational descriptive study reports the results of 7200 cases of mini Lch performed at Ibrahim General Hospital and Eden Multi-care hospital, Dhaka, Bangladesh by a single surgeon. From May 1998 till July 2013in total 8700 patients were offered Mini-lch and 7200 procedures were completed successfully. The operative indication, total operative time, conversion rate, hospital stay, patient satisfaction, post operative pain, complications, morbidity and mortality were reviewed. In this series conversion to open surgery was 0.39%. Average operating time was 30.22 minutes. Early acute cases (9%) did not require conversion to open. Average post operative hospital stay was 21 hours. There was no mortality in the series. Six patients developed incisional hernia at the umbilical port site and 16 patients had umbilical wound infection. Patient acceptance was excellent, postoperative analgesic requirement was less. With Mini Lch better cosmetic result was achieved, recovery was early. Minilaparoscopic cholecystectomy is an economically feasible, and more acceptable considering the cosmetic outcome and patient acceptance. Our results indicate that this procedure could be performed successfully and safely by experienced surgeons. PMID- 27277362 TI - Factors Associated with Periodontal Disease in Pregnant Diabetic Women. AB - There have been an association between systemic diseases and hormonal changes particularly diabetes which has been cited as a risk factor in the progression of periodontitis in pregnant women. The incidence and severity of periodontal diseases are increasing at a higher rate and a common condition in pregnant diabetic women among Bangladeshi population. This cross sectional study included 200 pregnant women who were selected from gynecological department and examined at the dental unit. The clinical parameters used were the Silness and Loe plaque index (PI), gingival scores and periodontal status and any relationship to socio demographic variables (age, occupation, level of education and urban or rural residence) and clinical variables (gestation period, previous pregnancy, type of diabetes and periodontal maintenance) were evaluated. The results showed that these clinical parameters increased concomitantly with an increase in the stage of pregnancy and in women with multiple pregnancies. Increased age, lower level of education, unemployment and patients residing in rural areas were associated with significantly higher gingival scores and periodontal measures. Women with increased age and multiple pregnancies usually have less interest to frequent periodontal maintenance showing a significant statistical relation between an increased age and changes in gingival and periodontal status; however no significant association was found between increased age and plaque index. It is concluded that gingival inflammatory symptoms are aggravated during pregnancy in diabetic women and are related to different clinical and demographic variables. PMID- 27277363 TI - Pattern of Head Injuries (Cranio-cerebral) due to Homicide in Association with Other Injuries: A Retrospective Post-mortem Study Autopsied at Dhaka Medical College Morgue House. AB - Annually, homicide contributes to a greater number of the total head injury cases. This retrospective study was conducted from 1(st) January 2009 to 31(st)December 2011 at Dhaka Medical College Mortuary. During this study period of three years a total of 15300 autopsies were done of which 5649 cases (36.84%) were of head injuries. Of them 747(13.22%) were of homicidal, 4080(72.22%) road traffic accidents, 502(8.88%) accidental and 320(5.66%) cases of fall from heights. Three hundred ninety eight (398) urban cases (53.27%) out numbered 307 rural cases (41.09%) followed by 42 unknown cases (5.62%). Most cases belong to the younger age group i.e. 21-40 years (43.34%) with male preponderance 470(63.10%). Defense wounds were present in 281 cases (37.82%) out of the total 747 homicidal head injuries. There were 206(27.57%) upper limb, 176(23.56%) spinal, 139(18.60%) abdominal, 135(18.07%) thoracic, 58(7.76%) lower limb and 33(4.41%) pelvic injuries found as associated injury. There were 258(34.53%) fractures of occipital followed by 209(28.29%) parietal, 113(15.01%) frontal, 104(13.75%) temporal, 24(3.21%) ant. Cranial fossa, 23(3.07%) post. Cranial fossa and 16(2.08%) of middle cranial fossa fractures. Extradural haemorrhage was more i.e. 434 cases (58.43%) followed by subdural, combination of all, subarachnoid and intra-cerebral haemorrhages. Cases of concussion were more common i.e. 445(59.75%) than lacerated and combination of them. Blunt weapon tops the list of causative weapons i.e. 669(89.22%) than firearms 59(8.07%) and sharp pointed weapons 19(2.68%). PMID- 27277364 TI - Role of Serum Follicle Stimulating Hormone, Luteinizing Hormone, Testosterone and Prolactin Levels in Azoospermic Male Partner of Subfertile Couple. AB - This cross sectional study was carried out in the Infertility Unit, Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from January 2011 and June 2013. Eighty one (81) consecutive azoospermic male partner of married couple, aged 20-50 years with at least two years of subfertility and no known endocrinopathy and ejaculatory dysfunction were included in this study to find out their abnormal hormonal pattern. None of them had received any form of treatment within the last 3 months prior to hormonal evaluation. Men with hypertension, recent fever, chemo or radiation exposure were excluded from the study. Eight weeks interval two semen analyses were done in the Andrology Laboratory of above department following standard WHO guideline, 2004. Using standard ELISA technique, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin were measured/assayed/estimated. The results of this study demonstrated that 40 (49.4%) men had normal endocrine pattern against 51 (50.6%) with endocrinopathy. The former may be related to obstructive azoospermia, which needs further analyses. Both the increased FSH (>11.1mIU/ml) and LH (>7.6mIU/ml) were observed in 25 (30.9%) men, only elevated FSH (>11.1mIU/ml) in 9(11.1%), and only elevated LH (>7.6mIU/ml) in 7(8.6%). Low testosterone level (<270ng/dl) was observed in 11(13.6%), low TSH (<0.4MUIU/ml) in 1(1.2%) and low prolactin (<2.5ng/dl) in 5(6.2%). PMID- 27277365 TI - Presentation and Treatment Outcomes of 100 Lupus Nephritis Patients: Single Center Study. AB - Over a period of 3 years (January 2011 to December 2013) 100 cases of Lupus nephritis patients admitted in nephrology department of Bangabandhu Sheikh Mujib Medical University (BSMMU) were evaluated. Their clinical characteristics, biochemical parameters, renal histology according to WHO classification were categorized and their treatment modalities and outcome was observed. Among 100 patients, 84 were female and 16 were male, with F:M ratio 5:1. Mean age of female were 23+/-4 years and male were 29+/-4 years, mean BP in male was systolic 135+/ 8 mmHg, diastolic 80+/-9mmHg and in female systolic was 130+/-7mmHg, diastolic 75+/-6 mmHg, mean Serum Creatinine for male was 180+/-12MUmol/L and mean serum creatinine in female was 170+/-20MUmol/L. Sixty five percent (65%) patient showed extra renal manifestation. All patients presented with proteinuria, among them 45% were nephrotic presentation, 25% patients presented with acute nephritic illness, 15% were nephritic nephrotic, 10% patients had rapidly progressing glomerulonephritis (RPGN), and 5% were with asymptomatic proteinuria. Renal biopsy of 100 patient according to WHO classification showed class I - 5%, class II - 20%, class III - 26%, class IV - 35%, class V - 8%, class VI - 6%. Immunosuppressive protocol used was prednisolone and cyclophorphamide in the majority of patients in class III to class VI LN patients. Few patients received prednisolone and mycophenolate mofetil. Twenty four percent (24%) patients were in complete remission during this study period and 12% developed end stage renal disease (ESRD). Seventy six percent (76%) patients passed through various stages of CKD, majority of them were in CKD stage IV and stage III, and few were in CKD stage I and stage II. About 70% of the participants had suffered from one or more complications, where majority were infections. Infections and renal failure were the leading cause of death in our study. PMID- 27277366 TI - Comparison between Decompressive Craniectomy with Durotomy and Conservative Treatment in Spontaneous Supratentorial Intracerebral Hemorrhage. AB - Large Intracerebral hematoma (ICH), compounded by perihematomal edema can produce severe elevations of intracranial pressure (ICP). Decompressive craniectomy (DC) beneficially addresses mass effect. Therefore this study is aimed to prove that decompressive craniectomy with durotomy has better outcome in patients with spontaneous supratentorial ICH than conservatively treated patients. This Quasi Experimental study was carried out in the Department of Neurosurgery, Dhaka Medical College & Hospital (DMCH), Dhaka, Bangladesh from July 2012 to December 2013 using purposive sampling procedure. A total of 80 admitted adult hypertensive patients with spontaneous supratentorial ICH were enrolled in the study population fulfilling all selection criteria. Of them 40 patients underwent decompressive craniectomy with durotomy was considered as surgical group and 40 patients were treated conservatively was considered as conservative group. All the cases were continuously followed up and GCS score at 7(th) day of treatment (D7) and at discharge was recorded. Mean+/-SD hematoma volume was 56.91+/-13.72ml in surgical patients and in conservative group 51.80+/-13.58ml. Outcome measured by modified Rankin Scale at 3 months. Sixty percent (60%) patients had good outcome (mRS 0-4) and 40% patients had poor outcome (mRS 5-6) in surgical group. On the other hand, 52.5% patients had good (mRS 0-4) and 47.5% had poor (mRS 5-6) outcome in conservative group. In logistic regression analysis, conservative group was 3.643 times more prone to develop poor outcome than surgical group which was statistically significant (95% CI, 1.040-13.047; p value <0.05) and volume of hematoma [OR (95% CI), 1.131(1.059-1.207); p value <0.001)] was the most important predictor of outcome. This study indicates that decompressive craniectomy with preservation of brain integrity in patients with spontaneous supratentorial ICH is feasible and safe. It can be a useful alternative surgical procedure in the treatment of spontaneous supratentorial ICH. PMID- 27277367 TI - Prognostic Role of Multiple Cardiac Biomarkers in Newly Diagnosed Acute Coronary Syndrome Patients. AB - Acute coronary syndrome includes unstable angina and myocardial infarction with or without ST-segment elevation, is life-threatening disorders that remain a source of high morbidity and mortality despite advances in treatment. The aim of the study was to evaluate the prognostic role of serum cTnI, CK-MB, hsCRP, MPO and BNP in newly diagnosed acute coronary syndrome patients. This cohort study was carried out in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University in cooperation with the Department of Cardiology, BSMMU and NICVD during the period of March 2013 to February 2014. A total 100 newly diagnosed acute coronary syndrome patients were purposively enrolled in this study within 24 hours of attacked, among them 30 were NSTEMI, 65 were STEMI and 5 were unstable angina. Serum cTnI, CK-MB, hsCRP, MPO and BNP concentrations were measured at enrollment and grouping of the study subjects were done on the basis of their empirical cut off values into two groups. In cTnI: Group I (n=20) having cTnI <4ng/ml and Group II (n=80) having cTnI >=4ng/ml. In CK-MB: Group I (n=18) having CK-MB <10ng/ml and Group II (n= 82) having CK-MB >=10ng/ml. In hsCRP: Group I (n=36) having hsCRP <5mg/L and Group II (n=64) having hsCRP >=5mg/L. In MPO: Group I (n=30) having MPO <285.5pmol/L and Group II (n=70) having MPO >=285.5pmol/L. In BNP: Group I (n=26) having BNP <135pg/ml and Group II (n=74) having BNP >=135pg/ml. All the study subjects were treated and managed identically by standard management protocol and were followed up periodically up to three months from the onset of events during hospital stay and after discharge. Clinical outcomes of the study subjects such as good recovery, morbidity (recurrent ACS, heart failure, arrhythmia and revascularization) and mortality were evaluated with respect to their base line cTnI, CK-MB, hsCRP, MPO and BNP concentrations. Increased levels of base line cardiac biomarkers in Group II patients showed significantly high morbidity and mortality cTnI (p=0.044), CK MB (p=0.045), hsCRP (p=0.009), MPO (p=0.003), and BNP (p=0.001) in compared to Group I. In relative risk ratio analysis showed significantly worse outcome in Group II acute coronary syndrome patients in comparison to Group I. In case of cTnI RR - 1.85 at 95% CI 1.19-2.88, in case of CK-MB RR- 1.88 at 95% CI 1.21 2.92, in case of hsCRP RR- 2.05 at 95% CI 1.30-3.25, in case of MPO RR- 2.59, at 95% CI 1.49-4.49, and in case of BNP RR- 3.47 at 95% CI 2.5-5.36. It was concluded from this study that base line serum cTnI, CK-MB, hsCRP, MPO, and BNP can be used clinically as prognostic biomarkers of acute coronary syndrome. PMID- 27277368 TI - Does Education Have Any Influence on Symptom Score of IBS Patients: A Randomized Controlled Study. AB - Despite much research, the pathophysiology of IBS remains poorly understood. So it is very difficult to treat. There is no standard treatment for IBS. Because IBS symptoms can be elicited or exacerbated by diet and stress, this suggests that patient education regarding his or her illness might be beneficial to patients in managing their symptoms. This study was done to see the short term effects of outpatient education in relation to change of symptom score in IBS patients. This is a prospective randomized comparative study. In this study a total of 80 patients were included. Forty patients were given only pharmacological management with Mebevarine hydrochloride 135mg thrice daily half an hour before meal and Amitryptline 10mg at night for six months and another forty were given education in addition to the same pharmacological treatment. In both the study group [medical management only versus medical management with education] changes of symptoms and quality of life of patients of IBS were assessed by using previously used, specially designed symptoms scoring system and a validated IBS-QOL instrument. There was no significant difference in severity of symptoms between only drug treatment group (118.973) and education plus drug treatment group (119.57) before treatment. The difference of improvement between the education group and without education group was not statistically significant (P>0.05), though the subsidence of pain in both the group before and after treatment was statistically significant (P<0.01). PMID- 27277369 TI - Relationship between Serum Iron Profile and Blood Groups among the Voluntary Blood Donors of Bangladesh. AB - Blood donation results in a substantial iron loss and subsequent mobilization from body stores. Chronic iron deficiency is a well-recognized complication of regular blood donation. The present study conducted to compare the level of serum ferritin, serum iron, total iron binding capacity (TIBC) and percentage transferrin saturation in different ABO and Rhesus type blood groups among the voluntary blood donors of Bangladesh. The present prospective study included 100 healthy voluntary donors attending at Department of Blood Transfusion, Dhaka Medical College, Dhaka between the periods of July 2013 to Jun 2014. From each donor 10mL venous blood sample was taken and divided into heparinized and non heparinized tubes for determination of hemoglobin (Hb), hematocrit (Hct), serum iron (SI), total iron binding capacity (TIBC) and serum ferritin by standard laboratory methods. Percentage of transferrin saturation (TS) calculated from serum iron and TIBC. Data were analyzed with SPSS (version 16) software and comparisons between groups were made using student's t-test and one way ANOVA. In the present study mean+/-SD of age of the respondents was 27.2+/-6.5 years with a range of 18 to 49 years and 81.0% were male and 19.0% were female. Among the donors 18.0% had blood group A, 35.0% had blood group B, 14.0% had blood group AB and 33.0% had blood group O. Among the donors 91.0% had rhesus positive and 9.0% had rhesus negative. Donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels. Donors with blood group A had highest TIBC level. Donors with blood group B had lowest serum ferritin level. An independent samples 't' test showed statistically significant difference in serum ferritin and percentage transferrin saturation between blood group AB and blood group O and in percentage transferrin saturation between blood group B and blood group O. One way ANOVA showed that there is no significant difference in haemoglobin, serum iron, serum ferritin and percentage transferring saturation in different ABO and Rh blood grouping categories. Blood donors with blood group O had lowest haemoglobin, serum iron and transferring saturation levels and donors with blood group A had highest TIBC level. Blood donors with blood group B had lowest serum ferritin level. The understanding of the different blood groups ability to retain iron in their system can give an insight into their ability to handle the disease iron deficiency anaemia. PMID- 27277370 TI - Anatomical and Morphological Characterization of the Nasopalatine Canal: A Cone Beam Computed Tomography Study. AB - The anterior maxilla, also called pre-maxilla, is an area frequently requiring surgical interventions. Rehabilitation of this area remains a complex restorative challenge. The most prominent anatomical structure within the anterior maxilla is the Nasopalatine Canal. Thorough knowledge about this anatomical structure plays an important role in the successful outcomes of surgical procedures. This retrospective study was done to evaluate the anatomy and morphology of the Nasopalatine Canal using cone-beam computed tomography (CBCT). The study included 125 subjects aged between 15 and 78 years who were divided into the following 5 groups: i) 15-30 years, ii) 30-45 years, iii) 45-60 years, iv) 60-75 years, v) >=75 years in the Department of Oral Medicine & Radiology, Sri Aurobindo College of Dentistry, Indore, Madhya Pradesh, India from January 2012 to January 2015. Cone-beam computed tomography (CBCT) was performed using a standard exposure and patient positioning protocol. The data of the CBCT images were sliced in three dimensions. Image planes on the three axes (X, Y, and Z) were sequentially analyzed for the location, morphology and dimensions of the Nasopalatine Canal. The correlation of age and gender with all the variables were evaluated. ANOVA and Z-test was used. P value <0.05 was considered statistically significant. Males and females showed significant differences in the length of the canal and anterior bone width in the sagittal sections. Inverted L was identified as a new dimension to the morphological shape of Nasopalatine Canal in central Madhya Pradesh population. The present study highlighted important variability observed in the anatomy and morphology of the Nasopalatine Canal. PMID- 27277371 TI - A 47 Years Lady with Intrathoracic Lipoma. AB - A case of a 47 years old female who presented to Mymensingh Medical College Hospital, Medicine Unit-5, complaining of severe dyspnea and occasional leg swelling. Chest X-ray, USG of chest and chest CT scan revealed a right sided giant intrathoracic mass extending across the posterior mediastinum into the left chest cavity. CT guided FNAC of right lung revealed lipoma. PMID- 27277372 TI - Small Bowel Perforation during Suprapubic Trocar Cystotomy: A Case Report. AB - A 35 years old man presented with retention of urine secondary to meatal stenosis with bulbar urethral stricture. He had a distended, palpable, tender urinary bladder. Urethral catheterization and dilatation was tried but failed. A trocar cystostomy was performed under local anaesthesia, which led to the injury to the small bowel when least expected. This is a rare but well recognized complication of small bowel injury following blind trocar suprapubic cystostomy when it was least expected and as such had a significant bearing on its management. We discuss its subsequent management and possible mechanism underlying this unexpected and unfortunate complication in the given circumstances. PMID- 27277373 TI - Huge Perineal Tumour: A Rare Presentation of Gastrointestinal Stromal Tumour of Rectum. AB - Gastrointestinal stromal tumour (GIST) is a relatively rare neoplasm of gastrointestinal tract of which Rectal GIST is uncommon. It produces symptoms of per rectal bleeding or change in bowel habit. Recurrences following curative resection are predominantly intraabdominal, hepatic metastasis occurring at a median 20-25 months following the primary surgery. A 42 years old male presented a huge mass in hypogastrium, the size of which was reduced ofter neoadjuvant therapy for period of 1.5 years. He underwent abdominoperineal resection. He developed recurrences in perineum three times and in thigh at short intervals after primary resection. He also developed liver metastasis. He died two and half years after primary diagnosis. Rectal GIST should be included in differential diagnosis of intraabdominal mass and preoperative diagnosis based on histopathological as well as the immunohistochemical feature of the CD(117) and CD(34). Although complete surgical resection with negative tumour margin is the principal curative procedure for primary and non metastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients of rectal GIST. PMID- 27277374 TI - Bartter Syndrome with Normal Aldosterone Level: An Unusual Presentation. AB - Bartter syndrome (BS) is a hereditary disease, with an autosomal recessive or autosomal dominant mode of transmission. It is characterized by salt wasting hypochloraemic, hypokalaemic metabolic alkalosis and hyperreninaemia with normal blood pressure. The primary defect is in the thick ascending limb of loop of Henle (TAL). Herein, we report a case that had typical features of BS like severe dehydration, severe hypokalaemia, metabolic alkalosis and failure to thrive but had normal aldosterone level which is very uncommon. PMID- 27277375 TI - Left Atrial Myxoma in a Late Case of Lung Carcinoma. AB - Concomitant occurrence of lung carcinoma and an atrial myxoma is rare. We are reporting such a case, a 55 year old male, farmer, smoker for 30 years was under evaluation for his recent episode of stroke with hemiparesis during which an echocardiography showed presence of a left atrial myxoma and chest x-ray showed a lesion in the midzone of right lung. Fine needle aspiration cytology (FNAC) from enlarged right supraclavicular lymphnode revealed metastatic adenocarcinoma. Patient was referred to a tertiary cancer care hospital thereafter. PMID- 27277376 TI - A Case of Massive Pleural Effusion: Pleurodesis by Bleomycin. AB - Malignant pleural effusion is a common complication of primary and metastatic pleural malignancies. Pleurodesis for the management of malignant pleural effusion is intended to achieve symphysis between parietal and visceral pleura, and to prevent relapse of pleural effusion. Many chemical agents are tried to induce inflammation and damage of the pleural mesothelial layer to achieve this symphysis. Hemorrhagic pleural effusion, especially in the right hemithorax commonly occurs as presentation of primary and metastatic pleural malignancies. This case reports massive right-sided hemorrhagic pleural effusion as the sole manifestation of primary lung cancer in a 45 year old man. Patient attended our department of thoracic surgery complaining of cough, shortness of breath and right sided chest pain. A chest X-ray and chest computer tomography (CT) radiograph shows right sided massive pleural effusion. Right sided tube thoracotomy done. Pleural fluid study was done. Fluid for cytopathology was positive for malignant cell. Computed tomography guided fine needle aspiration cytology from right lung lesion was also done. Diagnosis was as small cell carcinoma. Pleural effusion resolved after 9(th) post operative day of chest tube insertion. Bleomycin pleurodesis was done. Day after pleurodesis intra thoracic tube was removed and patient was discharged from hospital on 10(th) Post operative day with an advice to attend the oncology department for further treatment. The protocol of tube thoracostomy and chemical pleurodesis was almost always successful in giving symptomatic relief of respiratory distress for a considerable period of time. However, chemical pleurodesis is not possible in all cases of malignant pleural effusion because it has got potential complication including death. PMID- 27277377 TI - Niemann-Pick Disease Type B in a 21 Year Old Male. AB - Niemann-pick disease is a group of autosomal recessive disorder of lipid storage with progressive accumulation of sphingomyelin and other lipids in the lysosomes of various tissues. We are reporting a 21 year old male who had hepatosplenomegaly, cherry red macula and normal cognitive function. Bone marrow biopsy showed plenty of foam cells and sphingomyelinase level was low, thus conforming our diagnosis. Survival into adulthood and absence of gross neurological involvement suggests Niemann-Pick disease type B. PMID- 27277378 TI - A Patient with Grave's Disease and Tuberculous Lymphadenitis. AB - Immune reactivity between Mycobacteria and human antigens can play an important role in the pathogenesis of autoimmune disease. We report a case of Graves's disease and tuberculous lymphadenitis to explain the mechanism of correlation between immune-mediated diseases and tuberculosis and to raise awareness of the importance of screening for TB in this context, especially in endemic country. Screening for latent TB at immune mediated disease diagnosis and regular timely screening thereafter may be beneficial. PMID- 27277379 TI - Cutaneous Tuberculosis: An Update. AB - Among extra pulmonary tuberculosis cutaneous tuberculosis occurs rarely, despite a high and increasing prevalence of tuberculosis worldwide particularly in developing countries. Cutaneous tuberculosis can be acquired exogenously or endogenously and present as a diverse of differing clinical morphologies. Diagnosis of these lesions can be difficult, as they resemble many other dermatological conditions that are often primarily considered. Moreover, microbiological confirmation is poor, despite scientific advances, such as the more frequent use of polymerase chain reaction. Furthermore, treatment of cutaneous tuberculosis is also challenging in many cases. PMID- 27277380 TI - Herd Immunity: A Brief Review. AB - Immunization is a means of protecting the greatest number of people. By reducing the number of susceptible in the community, it augments "herd immunity" making the infection more difficult to spread. It also reduces the risk for those individuals who have escaped vaccination or those who have not developed satisfactory protection. It is well to bear in mind that immunizations are not at all 100 per cent effective, particularly when an individual is exposed to a large dose of pathogenic organisms. PMID- 27277381 TI - The impact of familiarization strategies on the missing-letter effect. AB - When reading a text and searching for a target letter, readers make more omissions of the target letter if it is embedded in frequent function words than if it is in rare content words. While word frequency effects are consistently found, few studies have examined the impacts of passage familiarity on the missing-letter effect and studies that have present conflicting evidence. The present study examines the effects of passage familiarity, as well as the impacts of passage familiarization strategy promoting surface or deep encoding, on the missing-letter effect. Participants were familiarized with a passage by retyping a text, replacing all common nouns with synonyms, or generating a text on the same topic as that of the original text, and then completed a letter search task on the familiar passage as well as an unfamiliar passage. In Experiment 1, when both familiar and unfamiliar passages use the same words, results revealed fewer omissions for the retyping and synonyms conditions. However, in Experiment 2, when different words are used in both types of texts, no effect of familiarization strategy was observed. Furthermore, the missing-letter effect is maintained in all conditions, adding support to the robustness of the effect regardless of familiarity with the text. PMID- 27277382 TI - Selection and evaluation of micro-organisms for biocontrol of Verticillium dahliae in olive. AB - AIMS: To identify potential biological control agents against Verticillium wilt in olive through a mass screening approach. METHOD AND RESULTS: A total of 47 strains and nine mixtures of micro-organisms were evaluated against Verticillium dahliae in a three stage screening: (i) in vitro, by the effect on the mycelial growth and spore germination of the pathogen; (ii) in natural infested soil, by the effect on the reduction of microsclerotia of the pathogen; (iii) in planta, by the effect on the infection of olive plants under controlled conditions. Various fungal and bacterial strains and mixtures inhibited the pathogen and showed consistent biocontrol activity against Verticillium wilt of olive. CONCLUSION: The screening has resulted in promising fungi and bacteria strains with antagonistic activity against Verticillium, such as two non-pathogenic Fusarium oxysporum, one Phoma sp., one Pseudomonas fluorescens and two mixtures of micro-organisms that may possess multiple modes of action. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides a practical basis for the potential use of selected strains as biocontrol agents for the protection of olive plants against V. dahliae infection. In addition, our study presented an effective method to evaluate antagonistic micro-organisms of V. dahliae in olive. PMID- 27277383 TI - Immature ovarian teratoma with hyponatremia and low serum vasopressin level. AB - Hyponatremia is often caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Hypersecretion of vasopressin from malignant tumors can be considered a cause of SIADH. Most of these ectopic productions of vasopressin are complications of small cell lung cancer. Cases concomitant with ovarian tumors are very rare, and a specific causative substance from the ovary is often unknown. A 16-year-old woman was diagnosed with an ovarian tumor. She developed hyponatremia that was resistant to medical treatment, but immediately improved after surgical resection of the tumor. Her diagnosis was SIADH caused by an ovarian tumor; however, her serum vasopressin level was normal. It is possible that a vasopressin-like substance causing SIADH was secreted by either nervous system tissue within an immature teratoma or small cell lung cancer. We should be cautious when SIADH is a complication of an ovarian tumor. PMID- 27277384 TI - Regulation of CBL and ESR1 expression by microRNA-22-3p, 513a-5p and 625-5p may impact the pathogenesis of dust mite-induced pediatric asthma. AB - Despite evidence for the involvement of microRNAs (miRNAs or miRs) in pediatric asthma, the mechanism responsible has not yet been fully elucidated. We aimed to identify novel miRNAs and to study their pathogenic role(s) in children with dust mite-induced asthma in order to gain a better understanding of the underlying mechanism responsible for this disease. For this purpose, 62 patients with asthma as well as 62 age- and gender-matched healthy controls were recruited. Twelve pairs of subjects were randomly subjected to microarray-based discovery analysis using a miRCURY LNATM array. The differential expression of miRNAs and their targeted messenger RNAs were validated using RT-qPCR. Plasma concentrations of cytokines were determined using an enzyme-linked immunosorbent assay (ELISA) kit. The results revealed that three novel miRNAs - miR-22-3p, miR-513a-5p and miR-625 5p - were significantly downregulated in the asthma group compared with the control group (p<0.01), whereas the transcript levels of Cbl proto-oncogene, E3 ubiquitin protein ligase (CBL), peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B), and estrogen receptor 1 (ESR1) that are targeted by these miRNAs were increased (p<0.01). There were significant differences in the plasma concentrations of gamma-interferon, tumor necrosis factor-alpha, interleukin (IL)-12 and IL-10 between the two groups (p<0.05). Thus, miR-513a-5p, miR-22-3p and miR-625-5p may have an impact on the regulation of the immune response and inflammatory cytokine pathways through the regulation of their target gene(s), CBL, PPARGC1B and ESR1, which may then lead to a dust mite induced asthma attack. Our findings may provide novel insights into the pathogenesis of pediatric asthma. PMID- 27277385 TI - RIN2 syndrome: Expanding the clinical phenotype. AB - Biallelic defects in the RIN2 gene, encoding the Ras and Rab interactor 2 protein, are associated with a rare autosomal recessive connective tissue disorder, with only nine patients from four independent families reported to date. The condition was initially termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis), based on the clinical features of the first identified family; however, with the expansion of the clinical phenotype in additional families, it was subsequently coined RIN2 syndrome. Hallmark features of this condition include dysmorphic facial features with striking, progressive facial coarsening, sparse hair, normal to enlarged occipitofrontal circumference, soft redundant and/or hyperextensible skin, and scoliosis. Patients with RIN2 syndrome present phenotypic overlap with other conditions, including EDS (especially the dermatosparaxis and kyphoscoliosis subtypes). Here, we describe a 10th patient, the first patient of Caucasian origin and the oldest reported patient so far, who harbors the previously identified homozygous RIN2 mutation c.1878dupC (p. (Ile627Hisfs*7)). Besides the hallmark features, this patient also presents problems not previously associated with RIN2 syndrome, including cervical vertebral fusion, mild hearing loss, and colonic fibrosis. We provide an overview of the clinical findings in all reported patients with RIN2 mutations and summarize some of the possible pathogenic mechanisms that may underlie this condition. (c) 2016 Wiley Periodicals, Inc. PMID- 27277386 TI - Pectus excavatum: echocardiographic, pathophysiologic, and surgical insights. AB - Patients with pectus excavatum (PEX) may be referred for echocardiographic examination for a variety of complaints including exercise intolerance, dyspnea, palpitations, or chest pain. It is therefore important for the echocardiographer to have an appreciation of the various abnormalities associated with this disorder. Echocardiographic imaging may reveal a number of structural alterations of the right ventricle as well as a reduction in right ventricular systolic function. Interestingly, a number of these abnormalities have also been described in patients with arrhythmogenic right ventricular dysplasia, although patients with PEX do not share a predilection for malignant ventricular arrhythmias. Additional echocardiographic abnormalities associated with PEX include prolapse of the mitral and/or tricuspid valves, Marfan's aortopathy, pericardial effusion, prominence of the crista terminalis, and possibly a number of congenital cardiac anomalies. This review discusses the echocardiographic abnormalities associated with PEX and their pathophysiologic significance. The effects of corrective orthopedic surgery on cardiac function are also discussed. PMID- 27277387 TI - Synthesis and evaluation of a (18) F-labeled 4-phenylpiperidine-4-carbonitrile radioligand for sigma1 receptor imaging. AB - We report the design and synthesis of several 4-phenylpiperidine-4-carbonitrile derivatives as sigma1 receptor ligands. In vitro radioligand competition binding assays showed that all the ligands exhibited low nanomolar affinity for sigma1 receptors (Ki (sigma1 ) = 1.22-2.14 nM) and extremely high subtype selectivity (Ki (sigma2 ) = 830-1710 nM; Ki (sigma2 )/Ki (sigma1 ) = 680-887). [(18) F]9 was prepared in 42-46% isolated radiochemical yield, with a radiochemical purity of >99% by HPLC analysis after purification, via nucleophilic (18) F(-) substitution of the corresponding tosylate precursor. Biodistribution studies in mice demonstrated high initial brain uptakes and high brain-to-blood ratios. Administration of SA4503 or haloperidol 5 min prior to injection of [(18) F]9 significantly reduced the accumulation of radiotracers in organs known to contain sigma1 receptors. Two radioactive metabolites were observed in the brain at 30 min after radiotracer injection. [(18) F]9 may serve as a lead compound to develop suitable radiotracers for sigma1 receptor imaging with positron emission tomography. PMID- 27277388 TI - Stable and null current hysteresis perovskite solar cells based nitrogen doped graphene oxide nanoribbons hole transport layer. AB - Perovskite solar cells are becoming one of the leading technologies to reduce our dependency on traditional power sources. However, the frequently used component poly(3,4-ethylenedioxythiophene) polystyrene sulfonate ( PEDOT: PSS) has several shortcomings, such as an easily corroded indium-tin-oxide (ITO) interface at elevated temperatures and induced electrical inhomogeneity. Herein, we propose solution-processed nitrogen-doped graphene oxide nanoribbons (NGONRs) as a hole transport layer (HTL) in perovskite solar cells, replacing the conducting polymer PEDOT: PSS. The conversion efficiency of NGONR-based perovskite solar cells has outperformed a control device constructed using PEDOT: PSS. Moreover, our proposed NGONR-based devices also demonstrate a negligible current hysteresis along with improved stability. This work provides an effective route for substituting PEDOT: PSS as the effective HTL. PMID- 27277389 TI - Failure pressures after repairs of 2-cm * 2.5-cm rhinologic dural defects in a porcine ex vivo model. AB - BACKGROUND: The objective of this study was to determine failure pressures of 6 rhinologic repair techniques of large skull base/dural defects in a controlled, ex vivo model. METHODS: Failure pressures of 6 dural repairs in a porcine model were studied using a closed testing apparatus; 24-mm * 19-mm dural defects were created; 40-mm * 34-mm grafts composed of porcine Duragen (Integra), fascia lata, and Biodesign (Cook) were used either with or without Tisseel (Baxter International Inc.) to create 6 repairs: Duragen/no glue (D/NG), Duragen/Tisseel (D/T), fascia lata/no glue (FL/NG), fascia lata/Tisseel (FL/T), Biodesign/no glue (B/NG), and Biodesign/Tisseel (B/T). Saline was infused at 30 mL/hour, applying even force to the underside of the graft until repair failure. Five trials were performed per repair type for a total of 30 repairs. RESULTS: Mean failure pressures were as follows: D/NG 1.361 +/- 0.169 cmH2 O; D/T 9.127 +/- 1.805 cmH2 O; FL/NG 0.200 +/- 0.109 cmH2 O; FL/T 7.833 +/- 2.657 cmH2 O; B/NG 0.299 +/- 0.109 cmH2 O; and B/T 2.67 +/- 0.619 cmH2 O. There were statistically significant differences between glued (Tisseel) and non-glued repairs for each repair category (p < 0.05). CONCLUSION: All glued repairs performed better than non glued repairs. Both D/T and FL/T repairs performed better than B/T repairs. No repair tolerated pressures throughout the full range of adult supine intracranial pressure. PMID- 27277390 TI - Alteration of transbilayer phospholipid compositions is involved in cell adhesion, cell spreading, and focal adhesion formation. AB - We previously showed that P4-ATPases, ATP10A/ATP8B1, and ATP11A/ATP11C have flippase activities toward phosphatidylcholine (PC), and aminophospholipids [phosphatidylserine (PS) and phosphatidylethanolamine], respectively. Here, we investigate the effect of PC-specific flippases versus aminophospholipid-specific flippases in cell spreading on the extracellular matrix. Expression of PC flippases, but not PS-flippases, delayed cell adhesion, cell spreading and inhibited formation of focal adhesions. In addition, overexpression of a PS binding probe that sequesters PS in the cytoplasmic leaflet delayed cell spreading and inhibited formation of focal adhesions. These results suggest that elevation of PC at the cytoplasmic leaflet of the plasma membrane by expression of PC-flippases may reduce the local concentration of PS or phosphoinositides, required for efficient cell adhesion, focal adhesion formation, and cell spreading. PMID- 27277391 TI - Promoter and Terminator Discovery and Engineering. AB - Control of gene expression is crucial to optimize metabolic pathways and synthetic gene networks. Promoters and terminators are stretches of DNA upstream and downstream (respectively) of genes that control both the rate at which the gene is transcribed and the rate at which mRNA is degraded. As a result, both of these elements control net protein expression from a synthetic construct. Thus, it is highly important to discover and engineer promoters and terminators with desired characteristics. This chapter highlights various approaches taken to catalogue these important synthetic elements. Specifically, early strategies have focused largely on semi-rational techniques such as saturation mutagenesis to diversify native promoters and terminators. Next, in an effort to reduce the length of the synthetic biology design cycle, efforts in the field have turned towards the rational design of synthetic promoters and terminators. In this vein, we cover recently developed methods such as hybrid engineering, high throughput characterization, and thermodynamic modeling which allow finer control in the rational design of novel promoters and terminators. Emphasis is placed on the methodologies used and this chapter showcases the utility of these methods across multiple host organisms. PMID- 27277392 TI - Engineering Biomolecular Switches for Dynamic Metabolic Control. AB - Living organisms have been exploited as production hosts for a large variety of compounds. To improve the efficiency of bioproduction, metabolic pathways in an organism are usually manipulated by various genetic modifications. However, bottlenecks during the conversion of substrate to a desired product may result from cellular regulations at different levels. Dynamic regulation of metabolic pathways according to the need of cultivation process is therefore essential for developing effective bioprocesses, but represents a major challenge in metabolic engineering and synthetic biology. To this end, switchable biomolecules which can sense the intracellular concentrations of metabolites with different response types and dynamic ranges are of great interest. This chapter summarizes recent progress in the development of biomolecular switches and their applications for improvement of bioproduction via dynamic control of metabolic fluxes. Further studies of bioswitches and their applications in industrial strain development are also discussed. PMID- 27277393 TI - Anaerobes in Industrial- and Environmental Biotechnology. AB - Anaerobic microorganisms present in diverse ecological niches employ alternative strategies for energy conservation in the absence of oxygen which enables them to play a key role in maintaining the global cycles of carbon, nitrogen, and sulfur, and the breakdown of persistent compounds. Thereby they become useful tools in industrial and environmental biotechnology. Although anaerobes have been relatively neglected in comparison to their aerobic counterparts, with increasing knowledge about their diversity and metabolic potential and the development of genetic tools and process technologies to utilize them, we now see a rapid expansion of their applications in the society. This chapter summarizes some of the developments in the use of anaerobes as tools for biomass valorization, in production of energy carriers and chemicals, wastewater treatment, and the strong potential in soil remediation. The ability of several autotrophic anaerobes to reduce carbon dioxide is attracting growing attention as a means for developing a platform for conversion of waste gases to chemicals, materials, and biofuels. PMID- 27277394 TI - Biological Processes for Hydrogen Production. AB - Methane is produced usually from organic waste in a straightforward anaerobic digestion process. However, hydrogen production is technically more challenging as more stages are needed to convert all biomass to hydrogen because of thermodynamic constraints. Nevertheless, the benefit of hydrogen is that it can be produced, both biologically and thermochemically, in more than one way from either organic compounds or water. Research in biological hydrogen production is booming, as reflected by the myriad of recently published reviews on the topic. This overview is written from the perspective of how to transfer as much energy as possible from the feedstock into the gaseous products hydrogen, and to a lesser extent, methane. The status and remaining challenges of all the biological processes are concisely discussed. PMID- 27277395 TI - Acknowledging Rural Disadvantage in Mental Health: Views of Peer Workers. AB - PURPOSE: The aim of this article was to present views and opinions of people employed to work from their personal experience of significant mental health challenges (peer workers). The specific focus was on their capacity to contribute meaningfully to mental health service provision and in rural areas and associated barriers. DESIGN AND METHODS: Grounded Theory was the methodology utilized. In depth interviews were conducted with peer workers throughout Australia. FINDINGS: Participants described significant barriers to the provision of quality mental health services in rural and regional locations. The two main areas identified were the following: transport and distance, and lack of mental health staff and services. CONCLUSIONS: The identified barriers place limitations on the capacity of peer workers to maximize effectiveness in rural settings. Peer workers could potentially play an important role in overcoming shortages of staff and services and improving mental health service delivery. PMID- 27277396 TI - Motor features in Parkinson's disease with normal olfactory function. AB - BACKGROUND: Normosmic Parkinson's disease (PD) might be a unique clinical phenotype with a more benign course when compared with hyposmic PD. OBJECTIVE: The objective of this study was to evaluate motor features and the acute levodopa response according to olfactory function. METHODS: A total of 169 de novo PD patients that underwent olfactory testing and acute levodopa challenge for clinical prediction of sustained long-term dopaminergic response were evaluated. RESULTS: The overall frequency of normosmia was 33%. Normosmic PD patients scored nonsignificantly different to hyposmic/anosmic patients on motor scale and on degree of improvement with levodopa. Motor scores at follow-up were comparable among groups. CONCLUSIONS: Normal olfactory function is common in early PD and was not associated with a different motor phenotype when compared with PD patients with olfactory dysfunction. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 27277397 TI - Identification of polymorphisms in Apolipoprotein M gene and their relationship with risk of recurrent venous thromboembolism. AB - Apolipoprotein M (ApoM) plasma levels have been reported to be associated with risk of venous thromboembolism (VTE) recurrence. However, the role of genetic alterations in the ApoM gene in VTE recurrence remains unknown. The aim of this study was to identify genetic aberrations in ApoM gene in VTE recurrence and their role in prediction of VTE recurrence in a prospective follow-up study of 1465 VTE patients. During follow-up, 156 (10.6 %) patients had VTE recurrence. First screening of whole ApoM gene was performed by Sanger's sequencing in selected age and sex matched non-recurrent and recurrent patients (n=95). In total six polymorphisms were identified and two polymorphisms (rs805297 and rs9404941) with minor allele frequency (MAF) >=5 % were further genotyped in the whole cohort by Taqman PCR. ApoM rs805297 polymorphism was significantly associated with higher risk of VTE recurrence in males but not in females on both univariate (p= 0.038, hazard ratio = 1.72, confidence interval = 1.03-2.88) and on multivariate analysis adjusted with mild and severe thrombophilia, family history, location and acquired risk factors for VTE. However, ApoM rs9404941 polymorphism showed no significant association with risk of VTE recurrence in all patients as well as in different gender groups. Moreover, ApoM rs805297 and rs9404941 polymorphisms were not associated with the ApoM plasma levels. In conclusion, for the first time we have sequenced whole ApoM gene in VTE and identified six polymorphisms. ApoM rs805297 was significantly associated with higher risk of VTE recurrence in male but not in female patients. PMID- 27277398 TI - Multiparametric magnetic resonance imaging and active surveillance: How to better select insignificant prostate cancer? AB - OBJECTIVES: To evaluate the role of multiparametric magnetic resonance imaging in improving the predictive accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria for active surveillance in prostate cancer. METHODS: A retrospective study was carried out with 126 prostate cancer patients treated with robot-assisted radical prostatectomy, but eligible for active surveillance according to the Prostate Cancer Research International: Active Surveillance criteria; 63 patients were also eligible according to the Epstein criteria. All patients underwent preoperative multiparametric magnetic resonance imaging, after at least 6 weeks from biopsy. The images from the multiparametric magnetic resonance imaging were assessed, and diagrams showing prostate sextants were used to designate regions of abnormalities within the prostate. Findings in the prostate were assigned to one of five categories according the Prostate Imaging-Reporting and Data System guidelines (v1.0), and considered positive for prostate cancer if the final Prostate Imaging-Reporting and Data System guidelines were >3 and negative if <=3. Multivariate logistic regression analysis was carried out to evaluate the gain in accuracy of the Prostate Cancer Research International: Active Surveillance and Epstein criteria when added to multiparametric magnetic resonance imaging. Decision curve analysis was carried out to identify the net benefit of each model. RESULTS: The inclusion of multiparametric magnetic resonance imaging to the Epstein criteria and the Prostate Cancer Research International: Active Surveillance multivariate model significantly increased their accuracy in predicting pathologically-confirmed insignificant prostate cancer by 7% and 5%, respectively. At the decision curve analysis evaluation, the model including the Prostate Cancer Research International: Active Surveillance criteria and multiparametric magnetic resonance imaging improved the clinical risk prediction over the other models. CONCLUSIONS: The present findings suggest that multiparametric magnetic resonance imaging is able to increase the predictive accuracy of Prostate Cancer Research International: Active Surveillance and Epstein criteria to identify prostate cancer patients eligible for active surveillance. PMID- 27277399 TI - Leucine-Rich Amelogenin Peptide (LRAP) Uptake by Cementoblast Requires Flotillin 1 Mediated Endocytosis. AB - Basic, pre-clinical, and clinical studies have documented the potential of amelogenin, and its variants, to affect cell response and tissue regeneration. However, the mechanisms are unclear. Thus, the aim of the present study was to identify, in cementoblasts, novel binding partners for an alternatively spliced amelogenin form (Leucine-Rich Amelogenin Peptide-LRAP), which is supposed to act as a signaling molecule in epithelial-mesenchymal interactions. LRAP-binding protein complexes from immortalized murine cementoblasts (OCCM-30) were achieved by capture affinity assay (GST pull down) and proteins present in these complexes were identified by mass spectrometry and immunoblotting. Flotillin-1, which functions as a platform for signal transduction, vesicle trafficking, endocytosis, and exocytosis, was identified and confirmed by co-precipitation and co-localization assays as a protein-binding partner for LRAP in OCCM-30 cells. In addition, we found that exogenously added GST-LRAP recombinant protein was internalized by OCCM-30 cells, predominantly localized in the perinuclear region and, that inhibition of flotillin1-dependent functions by small interference RNA (siRNA) methodology significantly affected LRAP uptake and its biological properties on OCCM-30 cells, including LRAP effect on the expression of genes encoding osteocalcin (Ocn), bone sialoprotein (Bsp), and runt-related transcription factor 2 (RunX2). In conclusion, LRAP uptake by cementoblast involves flotillin-assisted endocytosis, which suggests an involvement of LRAP in lipid-raft-dependent signaling pathways which are mediated by flotillin-1. J. Cell. Physiol. 232: 556-565, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27277400 TI - Interactions between Genetic and Ecological Effects on the Evolution of Life Cycles. AB - Sexual reproduction leads to an alternation between haploid and diploid phases, whose relative length varies widely across taxa. Previous genetical models showed that diploid or haploid life cycles may be favored, depending on dominance interactions and on effective recombination rates. By contrast, niche differentiation between haploids and diploids may favor biphasic life cycles, in which development occurs in both phases. In this article, we explore the interplay between genetical and ecological factors, assuming that deleterious mutations affect the competitivity of individuals within their ecological niche and allowing different effects of mutations in haploids and diploids (including antagonistic selection). We show that selection on a modifier gene affecting the relative length of both phases can be decomposed into a direct selection term favoring the phase with the highest mean fitness (due to either ecological differences or differential effects of mutations) and an indirect selection term favoring the phase in which selection is more efficient. When deleterious alleles occur at many loci and in the presence of ecological differentiation between haploids and diploids, evolutionary branching often occurs and leads to the stable coexistence of alleles coding for haploid and diploid cycles, while temporal variations in niche sizes may stabilize biphasic cycles. PMID- 27277401 TI - Evolution of Conspecific Brood Parasitism versus Cooperative Breeding as Alternative Reproductive Tactics. AB - Cooperative breeding and conspecific brood parasitism can both be favored by ecological saturation of breeding territories or nest sites. Here, we develop a model that links these alternative reproductive tactics by focusing on nonnesting females (S) that either breed cooperatively with a nesting female (N) or parasitize a third, outside host female (H). We find that cooperative breeding is more likely to evolve with increasing relatedness of cooperating females (S or N) to the outside host female (H) and with increasing costs to the hosts for receiving parasitic eggs. Conversely, cooperation is less likely with increasing kinship between the two potentially cooperative nesters (S and N). This is because even the nesting female gains higher inclusive fitness as long as the number of parasitic eggs (of her otherwise potentially cooperating partner) is sufficiently high. We find the relationship between kinship and reproductive skew within cooperative nests can be either positive or negative depending on the fecundity of parasites versus nesting females. We also find that either of the cooperatively nesting females is more likely to tolerate a smaller fraction of group reproduction as kinship with the host female increases and as the host reproduces more (relative to the parasite) in outside nests. Finally, our model predicts that, as the outside option of conspecific brood parasitism becomes more profitable, helping behavior (zero reproduction by one female) is less likely to evolve in cooperatively breeding groups. PMID- 27277402 TI - The Role of Within-Host Competition for Coexistence in Multiparasitoid-Host Systems. AB - Multiparasitism (females of multiple species parasitizing the same host) is a ubiquitous phenomenon in parasitoids, yet the role of within-host competition has been mostly ignored in multiparasitoid-host models. Here we study the effect of varying the degree of competition at different life stages: competition over oviposition sites (between-adult competition) and larval competition over resources within the host (within-host competition). We adapt a Nicholson-Bailey model to allow for varying levels of between-adult competition (varying the overlap in species distributions) and within-host competition (varying the number of offspring that can successfully emerge from a host). Surprisingly, while stronger between-adult competition reduces coexistence, stronger within-host competition promotes it. Asymmetric between-adult competition (a fecundity difference between the two species) reduces coexistence when compared to symmetric competition; this can be counteracted by asymmetric within-host competition (within-host competitive advantage of the lower-fecundity species), but only when within-host competition is strong and the correlation between the parasitoids' distributions is intermediate. We discuss our results in the context of the interaction between two parasitoid species, Nasonia vitripennis and Nasonia giraulti, which have strongly correlated distributions and high levels of multiparasitism in the field. We conclude that either low or asymmetric within host competition is unlikely to explain their coexistence. PMID- 27277403 TI - Successful by Chance? The Power of Mixed Models and Neutral Simulations for the Detection of Individual Fixed Heterogeneity in Fitness Components. AB - Heterogeneity in fitness components consists of fixed heterogeneity due to latent differences fixed throughout life (e.g., genetic variation) and dynamic heterogeneity generated by stochastic variation. Their relative magnitude is crucial for evolutionary processes, as only the former may allow for adaptation. However, the importance of fixed heterogeneity in small populations has recently been questioned. Using neutral simulations (NS), several studies failed to detect fixed heterogeneity, thus challenging previous results from mixed models (MM). To understand the causes of this discrepancy, we estimate the statistical power and false positive rate of both methods and apply them to empirical data from a wild rodent population. While MM show high false-positive rates if confounding factors are not accounted for, they have high statistical power to detect real fixed heterogeneity. In contrast, NS are also subject to high false-positive rates but always have low power. Indeed, MM analyses of the rodent population data show significant fixed heterogeneity in reproductive success, whereas NS analyses do not. We suggest that fixed heterogeneity may be more common than is suggested by NS and that NS are useful only if more powerful methods are not applicable and if they are complemented by a power analysis. PMID- 27277404 TI - Process-Based Species Pools Reveal the Hidden Signature of Biotic Interactions Amid the Influence of Temperature Filtering. AB - A persistent challenge in ecology is to tease apart the influence of multiple processes acting simultaneously and interacting in complex ways to shape the structure of species assemblages. We implement a heuristic approach that relies on explicitly defining species pools and permits assessment of the relative influence of the main processes thought to shape assemblage structure: environmental filtering, dispersal limitations, and biotic interactions. We illustrate our approach using data on the assemblage composition and geographic distribution of hummingbirds, a comprehensive phylogeny and morphological traits. The implementation of several process-based species pool definitions in null models suggests that temperature-but not precipitation or dispersal limitation acts as the main regional filter of assemblage structure. Incorporating this environmental filter directly into the definition of assemblage-specific species pools revealed an otherwise hidden pattern of phylogenetic evenness, indicating that biotic interactions might further influence hummingbird assemblage structure. Such hidden patterns of assemblage structure call for a reexamination of a multitude of phylogenetic- and trait-based studies that did not explicitly consider potentially important processes in their definition of the species pool. Our heuristic approach provides a transparent way to explore patterns and refine interpretations of the underlying causes of assemblage structure. PMID- 27277405 TI - Scaling of Morphological Characters across Trait Type, Sex, and Environment. AB - Biological diversity is, to a large extent, a matter of variation in size. Proportional (isometric) scaling, where large and small individuals are magnified versions of each other, is often assumed to be the most common way morphological traits scale relative to overall size within species. However, the many traits showing nonproportional (allometric) scaling have motivated some of the most discussed hypotheses on scaling relationships in biology, like the positive allometry hypothesis for secondary sexual traits and the negative allometry hypothesis for genitals. I evaluate more than 3,200 allometric parameters from the literature and find that negative allometry, not isometry, is the expected scaling relationship of morphological traits within species. Slopes of secondary sexual traits are more often steeper compared with other traits, but slopes larger than unity are also common for traits not under sexual selection. The steepness of the allometric slope is accordingly a weak predictor of past and present patterns of selection. Scaling of genitals varies across taxonomic groups, but negative allometry of genitals in insects and spiders is a consistent pattern. Finally, I find indications that terrestrial organisms may have a different scaling of morphological traits overall compared with aquatic species. PMID- 27277406 TI - Interspecific Functional Convergence and Divergence and Intraspecific Negative Density Dependence Underlie the Seed-to-Seedling Transition in Tropical Trees. AB - The seed-to-seedling transition constitutes a critical bottleneck in the life history of plants and represents a major determinant of species composition and abundance. However, we have surprisingly little knowledge regarding the forces driving this ontogenetic transition. Here we utilize information regarding organismal function to investigate the strength of intra- and interspecific negative density dependence during the seed-to-seedling transition in Puerto Rican tree species. Our analyses were implemented at individual sites and across an entire 16-ha forest plot, spanning 6 years. The functional richness of seedling assemblages was significantly lower than expected given the seed assemblages, but the functional evenness was significantly higher than expected, indicating the simultaneous importance of constraints on the overall phenotypic space and trait differences for successful transitions from seed to seedling. The results were consistent across years. Within species, we also found evidence for strong intraspecific negative density dependence, where the probability of transition was proportionally lower when in a site with high conspecific density. These results suggest that filtering of similar phenotypes across species and strong negative density dependence within and among species are simultaneously driving the structure and dynamics of tropical tree assemblages during this critical life-history transition. PMID- 27277407 TI - Dynamics of Adaptation in Experimental Yeast Populations Exposed to Gradual and Abrupt Change in Heavy Metal Concentration. AB - Directional environmental change is a ubiquitous phenomenon that may have profound effects on all living organisms. However, it is unclear how different rates of such change affect the dynamics and outcome of evolution. We studied this question using experimental evolution of heavy metal tolerance in the baker's yeast Saccharomyces cerevisiae. To this end, we grew replicate lines of yeast for 500 generations in the presence of (1) a constant high concentration of cadmium, nickel, or zinc or (2) a gradually increasing concentration of these metals. We found that gradual environmental change leads to a delay in fitness increase compared with abrupt change but not necessarily to a different fitness of evolutionary endpoints. For the nonessential metal cadmium, this delay is due to reduced fitness differences between genotypes at low metal concentrations, consistent with directional selection to minimize intracellular concentrations of this metal. In contrast, for the essential metals nickel and zinc, different genotypes are selected at different concentrations, consistent with stabilizing selection to maintain constant intracellular concentrations of these metals. These findings indicate diverse fitness consequences of evolved tolerance mechanisms for essential and nonessential metals and imply that the rate of environmental change and the nature of the stressor are crucial determinants of evolutionary dynamics. PMID- 27277408 TI - Soldiers in a Stingless Bee. AB - The differentiation of workers into morphological subcastes (e.g., soldiers) represents an important evolutionary transition and is thought to improve division of labor in social insects. Soldiers occur in many ant and termite species, where they make up a small proportion of the workforce. A common assumption of worker caste evolution is that soldiers are behavioral specialists. Here, we report the first test of the "rare specialist" hypothesis in a eusocial bee. Colonies of the stingless bee Tetragonisca angustula are defended by a small group of morphologically differentiated soldiers. Contrary to the rare specialist hypothesis, we found that soldiers worked more (+34%-41%) and performed a greater variety of tasks (+23%-34%) than other workers, particularly early in life. Our results suggest a "rare elite" function of soldiers in T. angustula, that is, that they perform a disproportionately large amount of the work. Division of labor was based on a combination of temporal and physical castes, but soldiers transitioned faster from one task to the next. We discuss why the rare specialist assumption might not hold in species with a moderate degree of worker differentiation. PMID- 27277409 TI - Can Clustering in Genotype Space Reveal "Niches"? AB - Community ecology lacks the success enjoyed by population genetics to quantify the relative roles played by deterministic and stochastic processes. It has been proposed that clustered patterns of abundance in genotype space provide evidence of selection in microbial communities, since no such clustering would arise in the absence of selection. We critique this test for its unrealistic null hypothesis. We show mathematically and with simulations that point mutations alone lead to clustering in genotype space by causing correlations between abundances of similar genotypes. We also show potential deviations from the mutation-only pattern caused by immigration from a source pool. Clustered patterns in genotype space may still be revealing of selection if analyzed quantitatively but only if neutral and selective regimes can be distinguished once mutation and immigration are included in the null model. PMID- 27277410 TI - The Adequate Use of Limited Information in Dispersal Decisions. AB - Several theoretical studies predict that informed (e.g., density-dependent) dispersal should generally result in lower emigration probabilities than uninformed (random) dispersal. In a 2012 publication, Bocedi et al. surprisingly come to the opposite conclusion. For most scenarios investigated, they found that noninformed and, particularly, less precisely informed dispersers evolve lower dispersal propensity than dispersers following "fully informed" strategies. Further, they observed that fully informed individuals evolved a steplike dispersal response-a response to local density that contradicts theoretical predictions for organisms with nonoverlapping generations. Replicating the individual-based simulations of Bocedi et al. we find that these conclusions are not justified and are based on a misinterpretation of simulation results: their controversial findings result from (i) a misleading use of the term "population density," (ii) a misconception concerning the true informative value of the different decision criteria they compared, and (iii) arbitrary constraints on the evolution of the dispersal response that prevented the evolution of strategies that allow for a fitness-enhancing utilization of available information. PMID- 27277411 TI - Models of Dispersal Evolution Highlight Several Important Issues in Evolutionary and Ecological Modeling. AB - Previous results showing that lack of information on local population density leads to higher emigration probabilities in unpredictable environments but to lower emigration probabilities in constant or highly predictable scenarios have recently been challenged by Poethke et al. By reimplementing both our model and that of Poethke and colleagues, we demonstrate that our original results indeed hold to the presented critiques and do not contradict previous findings. The comment by Poethke and colleagues does, however, present potentially intriguing results suggesting that negative density-dependent dispersal evolves under white noise for some model formulations. Here, through intermodel comparison, we seek to better understand the source of the differences in results obtained in our study and theirs. We conclude that the apparent negative density dependence reported by Poethke et al. is effectively density independence and that the shape of the reaction norm they obtain is a model artefact. Further, this response provides an opportunity to elaborate on some important issues in evolutionary and ecological modeling regarding (i) the importance of carefully considering different models' assumptions in comparisons among models, (ii) the need to consider the role of stochasticity and uncertainty when presenting and interpreting results from stochastic individual-based models, (iii) the adequate choice of the underlying ecological model that creates the selective pressures determining the evolution of behavioral reaction norms, and (iv) the appropriate choice of mutation models. PMID- 27277412 TI - Multiple Friends with Benefits: An Optimal Mutualist Management Strategy? AB - Most mutualisms in nature involve interactions between multispecies mutualist guilds and multiple partner species. While mechanisms such as niche partitioning can explain part of this diversity, the presence of low-quality partners, which produce relatively low returns on investment compared with other guild members, is not well understood. Here, we consider a novel explanation for this persistence: that low-quality partners are actively maintained by their hosts as part of a growth-maximizing strategy, even in the presence of higher-quality alternatives. We use a model inspired by the interaction between host trees and ectomycorrhizal fungi to demonstrate that when the environment is variable, trees maintain low-quality fungal partners that they would not otherwise maintain in constant environments. This active investment, which emerges as a response to saturating returns on investment in higher-quality partners, could contribute to the maintenance of diversity in multispecies mutualisms. PMID- 27277415 TI - 2015 American Society of Naturalists Awards. PMID- 27277413 TI - Within-Host Niche Differences and Fitness Trade-offs Promote Coexistence of Plant Viruses. AB - Pathogens live in diverse, competitive communities, yet the processes that maintain pathogen diversity remain elusive. Here, we use a species-rich, well studied plant virus system, the barley yellow dwarf viruses, to examine the mechanisms that regulate pathogen diversity. We empirically parameterized models of three viruses, their two aphid vectors, and one perennial grass host. We found that high densities of both aphids maximized virus diversity and that competition limited the coexistence of two closely related viruses. Even limited ability to simultaneously infect (coinfect) host individuals strongly promoted virus coexistence; preventing coinfection led to priority effects. Coinfection generated stabilizing niche differences by allowing viruses to share hosts. However, coexistence also required trade-offs between vector generalist and specialist life-history strategies. Our predicted outcomes broadly concur with previous field observations. These results show how competition within individual hosts and vectors may lead to unexpected population-level outcomes between pathogens, including coexistence, competitive exclusion, and priority effects, and how contemporary coexistence theory can help to predict these outcomes. PMID- 27277417 TI - Electromagnetically induced transparency metamaterial based on spoof localized surface plasmons at terahertz frequencies. AB - We numerically and experimentally demonstrate a plasmonic metamaterial whose unit cell is composed of an ultrathin metallic disk and four ultrathin metallic spiral arms at terahertz frequencies, which supports both spoof electric and magnetic localized surface plasmon (LSP) resonances. We show that the resonant wavelength is much larger than the size of the unit particle, and further find that the resonant wavelength is very sensitive to the particle's geometrical dimensions and arrangements. It is clearly illustrated that the magnetic LSP resonance exhibits strong dependence to the incidence angle of terahertz wave, which enables the design of metamaterials to achieve an electromagnetically induced transparency effect in the terahertz frequencies. This work opens up the possibility to apply for the surface plasmons in functional devices in the terahertz band. PMID- 27277416 TI - Expression of FOXM1 and related proteins in breast cancer molecular subtypes. AB - Forkhead box (FOX) proteins constitute an extended family of transcriptional regulators. FOXM1 is ubiquitously expressed in cells undergoing proliferation, and overexpression of FOXM1 is associated with poor prognosis in various malignant tumours. FOXM1 and FOXO3a are often transcriptionally antagonistic. FOXO3a plays a critical tumour-suppressive role in breast cancer. FOXO activity is modulated by its acetylation status, which is regulated by class III histone deacetylases (sirtuins; also known as SIRTs). This study evaluated the role of FOX proteins and their regulators in each molecular subtype of breast cancer. Immunohistochemical expressions of FOXM1, FOXO3a, SIRT1 and SIRT6 were evaluated in tissue microarray blocks containing 688 consecutive breast cancer samples. Mean expression levels were used to categorize tumours according to the expression of each protein (high or low). High expression of FOXM1 was significantly correlated with high SIRT1 and SIRT6 expression, higher histologic grade and triple-negative breast cancer (TNBC). High expression of nuclear FOXO3a and nuclear SIRT1 was correlated with a lower histologic grade and the hormone receptor-positive/HER2-negative subtype. In survival analysis, FOXM1 was an independent adverse prognostic factor for disease-free and overall survival in the hormone receptor-positive/HER2-negative subtype but not in the HER2-positive subtype or TNBC. In conclusion, although high FOXM1 expression was noted in the TNBC subtype, it had no prognostic impact in TNBC. However, it had prognostic significance in the hormone receptor-positive/HER2-negative subtype. PMID- 27277418 TI - Grape seed proanthocyanidins induce apoptosis through the mitochondrial pathway in nasopharyngeal carcinoma CNE-2 cells. AB - Although modern radiotherapy offers excellent local control in the treatment of nasopharyngeal carcinoma (NPC), current therapeutic decisions remain burdensome due to the frequency of local recurrence and treatment failure at distant sites. One potential and promising strategy for the prevention or treatment of cancers is the use of bioactive components of plant origin, including dietary plant products. Herein, we studied one class of these bioactive compounds, grape seed proanthocyanidins (GSPs), and explored their effect on NPC CNE-2 cells, as well as the primary mechanism underlying this effect. Our results revealed that treatment of human NPC CNE-2 cells with GSPs reduced cell viability in a dose- and time-dependent manner, and moreover, markedly induced cell cycle arrest at the G2/M phase, leading to induction of apoptosis. In addition, we found that the underlying mechanism was associated with increased expression of the pro apoptotic protein Bax, decreased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PRAP) protein, and the loss of mitochondrial membrane potential (MMP) (Deltapsim). Furthermore, GSPs upregulated the Bcl-2 homology 3 (BH3)-only proteins, Bim and Bad, in a concentration-dependent manner. Taken together, these data supported our hypothesis that, in human NPC CNE-2 cells, GSPs could induce apoptosis through the mitochondrial pathway and ultimately reduce cell viability. Collectively, the results discussed above provide substantive evidence for the potential of GSPs as an effective bioactive phytochemical for the treatment of NPC. PMID- 27277419 TI - Nodal marginal zone B cells in mice: a novel subset with dormant self-reactivity. AB - Marginal zone (MZ) B cells, representing a distinct subset of innate-like B cells, mount rapid T-independent responses to blood-borne antigens. They express low-affinity polyreactive antigen receptors that recognize both foreign and self structures. The spleen is considered the exclusive site for murine MZ B cells. However, we have here identified B cells with a MZ B-cell phenotype in the subcapsular sinuses of mouse lymph nodes. The nodal MZ (nMZ) B cells display high levels of IgM, costimulators and TLRs, and are represented by naive and memory cells. The frequency of nMZ B cells is about 1-6% of nodal B cells depending on mouse strain, with higher numbers in older mice and a trend of increased numbers in females. There is a significant expansion of nMZ B cells following immunization with an autoantigen, but not after likewise immunization with a control protein or with the adjuvant alone. The nMZ B cells secrete autoantibodies upon activation and can efficiently present autoantigen to cognate T cells in vitro, inducing T-cell proliferation. The existence of self-reactive MZ B cells in lymph nodes may be a source of autoantigen-presenting cells that in an unfortunate environment may activate T cells leading to autoimmunity. PMID- 27277420 TI - Food control and a citizen science approach for improving teaching of Genetics in universities. AB - A Citizen Science approach was implemented in the laboratory practices of Genetics at the University of Oviedo, related with the engaging topic of Food Control. Real samples of food products consumed by students at home (students as samplers) were employed as teaching material in three different courses of Genetics during the academic year 2014-2015: Experimental Methods in Food Production (MBTA) (Master level), and Applied Molecular Biology (BMA) and Conservation Genetics and Breeding (COMGE) (Bachelor/Degree level). Molecular genetics based on PCR amplification of DNA markers was employed for species identification of 22 seafood products in COMGE and MBTA, and for detection of genetically modified (GM) maize from nine products in BMA. In total six seafood products incorrectly labeled (27%), and two undeclared GM maize (22%) were found. A post-Laboratory survey was applied for assessing the efficacy of the approach for improving motivation in the Laboratory Practices of Genetics. Results confirmed that students that worked on their own samples from local markets were significantly more motivated and better evaluated their Genetic laboratory practices than control students (chi(2) = 12.11 p = 0.033). Our results suggest that citizen science approaches could not be only useful for improving teaching of Genetics in universities but also to incorporate students and citizens as active agents in food control. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):450-462, 2016. PMID- 27277421 TI - Hepatitis B and C surveillance and screening programmes in the non-EU/EEA Member States of the WHO European Region: survey findings from 10 countries, 2012. AB - The hepatitis B virus (HBV) and hepatitis C virus (HCV) epidemics warrant a comprehensive response based on reliable population-level information about transmission, disease progression and disease burden, with national surveillance systems playing a major role. In order to shed light on the status of surveillance in countries of the World Health Organization (WHO) European Region outside of the European Union and European Economic Area (EU/EEA), we surveyed 18 countries in Central and Eastern Europe. Among the 10 countries that responded, the common features of many surveillance systems included mandatory surveillance, passive case-finding and the reporting of both acute and chronic HBV and HCV. Only some countries had surveillance systems that incorporated the tracking of associated conditions and outcomes such as cirrhosis and liver transplantation. Screening programmes for some key populations appeared to be in place in many countries, but there may be gaps in relation to screening programmes for people who inject drugs, prisoners, sex workers and men who have sex with men. Nonetheless, important components of a surveillance structure are in place in the responding study countries. It is advisable to build on this structure to develop harmonised HBV and HCV surveillance for all 53 Member States of the WHO European Region following the example of the system recently instituted in EU/EEA countries. PMID- 27277422 TI - A novel DNMT1 mutation associated with early onset hereditary sensory and autonomic neuropathy, cataplexy, cerebellar atrophy, scleroderma, endocrinopathy, and common variable immune deficiency. AB - DNA methyltransferase 1 (DNMT1) is an enzyme which has a role in methylation of DNA, gene regulation, and chromatin stability. Missense mutations in the DNMT1 gene have been previously associated with two neurological syndromes: hereditary sensory and autonomic neuropathy type 1 with dementia and deafness (HSAN1E) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN). We report a case showing overlap of both of these syndromes plus associated clinical features of common variable immune deficiency, scleroderma, and endocrinopathy that could also be mutation associated. Our patient was found to be heterozygous for a previously unreported frameshift mutation, c.1635_1637delCAA p.(Asn545del) in the DNMT1 gene exon 20. This case displays both the first frameshift mutation described in the literature which is associated with a phenotype with a high degree of overlap between HSAN1E and ADCA-DN and early age of onset (c. 8 years). Our case is also of interest as the patient displays a number of new non neurological features, which could also be DNMT1 mutation related. PMID- 27277423 TI - TT2016 meeting report on the 13th Transgenic Technology meeting in Prague, Czech Republic. PMID- 27277424 TI - Comparison of the effects of ketamine and fentanyl-midazolam-medetomidine for sedation of rhesus macaques (Macaca mulatta). AB - BACKGROUND: This study assessed the effects of sedation using a combination of fentanyl, midazolam and medetomidine in comparison to ketamine. Rhesus Macaques (Macaca mulatta), (n = 16, 5 males and 3 females randomly allocated to each treatment group) received either ketamine (KET) (10 mg.kg(-1)) or fentanyl midazolam-medetomidine (FMM) (10 MUg/kg(-1); 0.5 mg.kg(-1); 20 MUg.kg(-1)) both IM. Oxygen (100%) was provided by mask and heart rate, blood pressure, respiratory rate, EtCO2 and depth of sedation were assessed every 5 min for 20 min. After the last time point, FMM monkeys were reversed with atipamezole naloxone (0.2 mg.kg(-1); 10 MUg.kg(-1)). Recovery was scored using clinical scoring scheme. Differences in physiological parameters and quality of sedation were compared using Area Under the Curve (AUC) method and either Mann-Witney or t student tests. RESULTS: Heart rate (beats/min) (Ket = 119 +/- 18; FMM = 89 +/- 17; p = 0.0066), systolic blood pressure (mmHg) (Ket = 109 +/- 10; FMM = 97 +/- 10; p = 0.0313), and respiratory rate (breaths/min) (Ket = 39 +/- 9; FMM = 29 +/- 10; p = 0.0416) were significantly lower in the FMM group. End-tidal CO2 (mmHg) did not differ between the groups (KET = 33 +/- 8; FMM = 42 +/- 11; p = 0.0462). Although some depression of physiological parameters was seen with FMM, the variables all remained within the normal ranges in both groups. Onset of a sufficient degree of sedation for safe handling was more rapid with ketamine (KET = 2.9 +/- 1.4 min; FMM = 7.9 +/- 1.2 min; p = 0.0009), but FMM recovery was faster (KET = 21.4 +/- 13.4 min; FMM = 9.1 +/- 3.6 min; p = 0.0379) and of better quality (KET = 1.3 +/- 0.9; FMM = 7.4 +/- 1.9; p = 0.0009) most probably because of the effectiveness of the reversal agents used. CONCLUSION: FMM provides an easily reversible immobilization with a rapid and good recovery quality and may prove a useful alternative to ketamine. PMID- 27277425 TI - Necrotizing herpetic retinopathy in an immune-compromised pediatric patient with minimal signs of inflammation: case report. AB - BACKGROUND: To report a case of necrotizing herpetic retinopathy(NHR) in an immuno-compromised pediatric patient. CASE PRESENTATION: An 11-year-old boy presented with a minimal ocular foreign-body sensation and peripheral visual field defect, as well as mild upper respiratory symptoms. He had undergone the Fontan operation for a ventricular septal defect and single ventricle during infancy, and had been taking oral steroids for 1 year immediately prior to his presentation to treat protein-losing enteropathy. Initially, a case of either cytomegalovirus (CMV) retinitis or acute retinal necrosis (ARN) was suspected, and an intravenous course of ganciclovir and acyclovir was therefore initiated. During treatment, varicella-zoster virus (VZV) was detected in the anterior chamber, and ARN was confirmed when both serum and aqueous humor were found by polymerase chain reaction (PCR) to be positive for VZV DNA. A peripheral retinal break and detachment developed after medical treatment, and a vitrectomy was performed. CONCLUSIONS: Typically, ARN is found in both healthy individuals and subclinically immuno-compromised patients of any age. CMV retinitis is somewhat more typical for immuno-compromised patients. Herein, we report a case of NHR in a pediatric patient with poor general condition and showing minimal signs of inflammation. PMID- 27277426 TI - Comparison of the accuracy of intraocular lens power calculations for cataract surgery in eyes after phototherapeutic keratectomy. AB - PURPOSE: To compare the accuracy of several methods of intraocular lens (IOL) power calculations used for cataract surgery in eyes treated with phototherapeutic keratectomy (PTK) that results in changes in the anterior corneal surface and axial length; these results make power calculations less predictable. METHODS: We evaluated the medical records of 23 eyes of 13 patients (mean age, 68.8 years; range 62-80 years) who underwent cataract surgery after PTK at Keio University Hospital, Tokyo, Japan. The prediction error, defined as the difference between the estimated postoperative spherical equivalent and the postoperative manifest refraction at the spectacle plane, was calculated using five formulas: SRK/T, Haigis-L, Shammas-PL, Camellin-Calossi, and OKULIX ray tracing software. We compared the median values of the arithmetic and absolute prediction errors among the five formulas. RESULTS: The median arithmetic errors after cataract surgery for the five formulas were 0.70 D (diopter) (range -0.41 to 2.78), -0.96 D (range -2.14 to 0.81), -0.81 D (range -1.89 to 1.15), -0.04 D (range -1.35 to 1.47), and 0.68 D (range -0.61 to 2.50), respectively. CONCLUSION: The Camellin-Calossi formula is a good option for calculating IOL powers in eyes that underwent PTK. PMID- 27277427 TI - How is Change in Physical Health Status Reflected by Reports of Nurses and Older People Themselves? AB - Background : Self-rated health is assumed to closely reflect actual health status, but older people's shifting norms and values may influence this association. We investigated how older people's change in self-ratings, in comparison to their retrospective appreciation and change in nurse ratings, reflect functional decline and mortality risk. Methods : A representative sample of 85-year olds from a middle-sized city in the Netherlands, excluding those with severe cognitive dysfunction, was followed for 6 years. Participants and a research nurse annually provided ratings of health, and participants retrospectively appreciated their annual change in health. Functional status was assessed with the Groningen Activity Rating Scale and all were followed for vital status. Results : Functional decline was reflected by all reports of change in health (all p < .001). When incongruent, change in nurse-ratings reflected functional decline better than change in self-ratings but retrospective appreciation reflected functional decline best (p < .001 vs change in self ratings and p < .05 vs change in nurse-ratings). Mortality risk was only reflected by retrospective appreciation (p < .01). Conclusions : Retrospective appreciation of health by older people is superior to change in self-ratings and nurse-ratings in reflecting change in physical health, possibly because similar norms and values are applied in the assessment. The nurse's norms, like the norms of older people, may shift with the ageing of the researched cohort. Asking people to retrospectively appreciate their change in health is a valuable addition to usual enquiries in practice and research. PMID- 27277429 TI - Family caregivers' reports of hospitalizations and emergency department visits in community-dwelling individuals with dementia. AB - Individuals with dementia in the United States have higher rates of hospitalizations and emergency department visits compared to those without. This descriptive study examined the frequency of hospitalizations and emergency department visits among community-dwelling individuals with dementia, reasons for hospitalizations and emergency department visits, and caregivers' actions to prevent these events. Family caregivers (n = 63) from education/support groups offered through Alzheimer's Association chapters in western Ohio completed a survey. Twenty-two percent of caregivers reported that their care recipient stayed overnight in the hospital and 30% reported that their care recipient visited the emergency department at least once in the past three months. The most frequent reasons for hospitalization and emergency department visits, such as urinary tract infections and fall-related injuries, were potentially avoidable. Caregivers reported giving medications, seeking healthcare services, and obtaining home care services, as the most frequently used preventive actions. Family caregivers of individuals with dementia should be provided substantive education about preventable hospitalizations and emergency department visits. PMID- 27277428 TI - Developmental Trajectory of Beta Cortical Oscillatory Activity During a Knee Motor Task. AB - There is currently a void in the scientific literature on the cortical beta oscillatory activity that is associated with the production of leg motor actions. In addition, we have limited data on how these cortical oscillations may progressively change as a function of development. This study began to fill this vast knowledge gap by using high-density magnetoencephalography to quantify the beta cortical oscillatory activity over a cross-section of typically developing children as they performed an isometric knee target matching task. Advanced beamforming methods were used to identify the spatiotemporal changes in beta oscillatory activity during the motor planning and motor action time frames. Our results showed that a widespread beta event-related desynchronization (ERD) was present across the pre/postcentral gyri, supplementary motor area, and the parietal cortices during the motor planning stage. The strength of this beta ERD sharply diminished across this fronto-parietal network as the children initiated the isometric force needed to match the target. Rank order correlations indicated that the older children were more likely to initiate their force production sooner, took less time to match the targets, and tended to have a weaker beta ERD during the motor planning stage. Lastly, we determined that there was a relationship between the child's age and the strength of the beta ERD within the parietal cortices during isometric force production. Altogether our results suggest that there are notable maturational changes during childhood and adolescence in beta cortical oscillatory activity that are associated with the planning and execution of leg motor actions. PMID- 27277430 TI - A collaborative clinical and population-based curriculum for medical students to address primary care needs of the homeless in New York City shelters : Teaching homeless healthcare to medical students. AB - Background Millions of Americans experience homelessness annually. Medical providers do not receive adequate training in primary care of the homeless.Methods Starting in 2012, a comprehensive curriculum was offered to medical students during their family medicine or ambulatory clerkship, covering clinical, social and advocacy, population-based, and policy aspects. Students were taught to: elicit specific social history, explore health expectations, and assess barriers to healthcare; evaluate clinical conditions specific to the homeless and develop plans for care tailored toward patients' medical and social needs; collaborate with shelter staff and community organizations to improve disease management and engage in advocacy efforts. A mixed methods design was used to evaluate students' knowledge, attitudes, and skills including pre- and post-curriculum surveys, debriefing sessions, and observed clinical skills.Results The mean age of the students (n = 30) was 26.5 years; 55 % were female. The overall scores improved significantly in knowledge, attitude, and self-efficacy domains using paired t-test (p < 0.01). Specific skills in evaluating mental health, substance abuse, and risky behaviours improved significantly (p < 0.05). In evaluation of communication skills, the majority were rated as having 'outstanding rapport with patients.'Conclusions Comprehensive and ongoing clinical component in shelter clinics, complementary teaching, experienced faculty, and working relationship and collaboration with community organizations were key elements. PMID- 27277431 TI - Hidden Reservoir: An Outbreak of Tuberculosis in Hospital Employees with No Patient Contact. AB - We describe an outbreak of tuberculosis (TB) in the food preparation area of a hospital, which demonstrates that employees in healthcare settings may serve as potential risks for spread of TB even if they have no direct patient contact. Infect Control Hosp Epidemiol 2016;37:1111-1113. PMID- 27277432 TI - Pulmonary manifestation of immunoglobulin G4-related disease in a 7-year-old immunodeficient boy with Epstein-Barr virus infection: a case report. AB - BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan fibroinflammatory condition with lymphoplasmacytic infiltrates containing abundant IgG4-positive plasma cells. The immunopathogenesis of the disease and the potential role of triggering autoantigens or infectious factors have not been clearly defined. Immunoglobulin G4-related lung disease is a new and emerging condition in pediatric patients and to date, there have been only two reports regarding pulmonary manifestation of IgG4-RD in children recently published. This is the first report of IgG4-related lung disease in an immunodeficient child with Epstein-Barr virus infection. CASE PRESENTATION: We report on the case of a 7 year old atopic boy who was hospitalized with an initial clinical and radiological diagnosis of pneumonia, positive Epstein-Barr virus (EBV)-DNA in the blood and defective adaptive immunity. The lung CT showed a consolidated mass lesion adjacent to the posterior wall of the chest and the diaphragm. The child underwent surgical resection of the tumor, and the histologic examination of the lung specimens revealed lymphoplasmacytic infiltrates with fibrosis and vasculitis correlating with IgG4-related lung disease. Subsequent monitoring of the patient with lung CT, pulmonary function tests and IgG4 levels did not show signs of active disease. CONCLUSIONS: The diagnosis of IgG4-related lung disease in children is challenging because of its rarity, nonspecific symptomatology and heterogeneous morphological manifestations. Further studies are required in children with pulmonary presentation of IgG4-RD to better understand pathogenesis of this condition, possible immunological or infectious triggering factors, and finally, to determine pediatric patient-targeted therapeutic interventions. PMID- 27277433 TI - Effects of extracts from Echinacea purpurea (L) MOENCH on mice infected with different strains of Toxoplasma gondii. AB - In recent years, due to the growing concern about recurrent epidemics by Toxoplasma gondii and other pathogens in Brazil, there has been an increase in the use of different preparations obtained from Echinacea purpurea in order to test their effectiveness against these infections. Although studies have suggested the beneficial effects of this species against the influenza virus, no data are available on the use of E. purpurea aqueous extract in T. gondii infections. Thus, the aim of this study was to analyze the effect of its administration in Swiss mice submitted to acute and prolonged infection with different T. gondii strains. This study showed that E. purpurea extract induced a significant reduction in the number of tachyzoites in the peritoneal fluid and liver imprints from mice infected by the RH strain. Moreover, prolonged treatment significantly increased the number of brain cysts of animals infected with ME 49 strain. The results obtained in this study suggest that the crude extract obtained from E. purpurea has important protective activities against infection with different T. gondii strains. PMID- 27277435 TI - Is newer better in the assessment of left ventricular diastolic function? Revival of left atrial size. PMID- 27277434 TI - First study on seroepidemiology and isolation of Toxoplasma gondii in free-range chickens in the semi-arid region of Paraiba state, Brazil. AB - The aim of this study was to investigate the seroprevalence and isolation of Toxoplasma gondii in free-range chickens in the state of Paraiba, northeastern Brazil. For this, blood samples were collected from 483 chickens in five municipalities in the state of Paraiba. The indirect immunofluorescence assay for anti-T. gondii antibodies was performed. The seropositive birds were slaughtered, and their brains and hearts were collected in order to perform a bioassay in mice. An epidemiological questionnaire was applied on the smallholdings visited, and univariable and multivariable logistic regressions were used to evaluate risk factors. The prevalence of chickens seropositive for T. gondii was found to be 31.5 % (152/483), and 86.1 % (56/65) of the smallholdings were positive. Among the 71 chickens subjected to bioassaying in mice, isolates of T. gondii were obtained from 33 (46.5 %). The isolates were named TgCkBrPB1 to 33. It was observed that the higher the chickens' antibody titer was, the greater the chance of isolating the parasite also was. Sixteen of the 33 isolates (48.5 %) were lethal for all the mice inoculated until 30 days post-inoculation. The risk factors for infection with T. gondii among these free-range chickens were extensive and semi-extensive rearing systems, smallholdings located in urban areas, and presence of cats. The results indicate that the prevalence of T. gondii among chickens in the state of Paraiba is high. Many parasites remained viable in the tissues of the birds studied, and presence of the protozoan was directly related to the management of these birds. PMID- 27277436 TI - First trimester ultrasound: current approaches and practical pitfalls. AB - Revolutionary technological improvements and high-frequency transvaginal scanning have enabled the resolution of ultrasound imaging in the first trimester to increase such that detailed early fetal development can now be well visualized. This investment in imaging technology has enabled not only normal embryonic development but also chromosomal abnormalities and structural anomalies to be more easily and accurately diagnosed before the second trimester. This article is intended to help radiologists in the interpretation and clinical application of normal and abnormal first trimester ultrasound findings in early pregnancy. We review the current literature and applications and interpretations of first trimester ultrasound. PMID- 27277437 TI - High-intensity focused ultrasound induced apoptosis with caspase 3, 8, and 9/6 activation in rat hepatoma. AB - PURPOSE: The purpose of the present study is to investigate anticancer efficacy and apoptosis confirmed by caspase under several exposure conditions of high intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Twenty-five rats with KDH-8 hepatoma were treated by HIFU at several acoustic energies to evaluate treatment efficacy. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and Hoechst 33258 staining, and caspase 3, 8, and 9/6 activity was respectively assayed. RESULTS: The KDH-8 subcutaneous tumors were reduced by HIFU, and these rats survived longer than the nontreatment rats (P < 0.01). The minimal threshold of HIFU energy was 30 W * 1.0 s for tumor control and long-term survival. The tumors exposed to HIFU exhibited marked apoptotic features under conditions of less than 10 W * 1.0 s. In cultured KDH-8 cells, apoptosis was caused at less than 30 W * 1.0 s (P < 0.01), and more was induced as the energy went down. Caspase 3, 8, and 9/6 were more activated at low energy under 10 W * 1.0 s (P < 0.01), and caspase 8, which is death receptor dependent, was significantly more activated than caspase 9/6, which is mitochondria dependent (P < 0.01). CONCLUSION: HIFU-induced apoptosis in vivo and in vitro is one of the mechanisms for tumor control and is mediated by caspase 3, 8, and 9/6. The significantly greater activation of caspase 8 than of caspase 9/6 suggests that the apoptosis pathway induced by HIFU might be more mitochondria dependent than death receptor dependent. However, further examination will be needed. PMID- 27277438 TI - Comparison of methods for evaluating bacterial contamination of ultrasound probes. AB - PURPOSE: To determine suitable methods for evaluating bacterial contamination of ultrasound probes. METHODS: We compared probe imprinting, swab streaking, and swab suspension methods for evaluating bacterial contamination of ultrasound probes. RESULTS: Experimental and clinical investigations showed that the sensitivity for detecting bacterial contamination of ultrasound probes was higher with probe imprinting than with swab methods. Probe imprinting was very simple and required only agar plates. CONCLUSION: Probe imprinting was the most suitable method for evaluating bacterial contamination of ultrasound probes. PMID- 27277440 TI - The ratio of the atrial areas reflects the clinical status of patients with pulmonary arterial hypertension. AB - PURPOSE: Echocardiography is useful not only for detecting pulmonary hypertension (PH) but also for estimating the severity of PH by evaluating various morphological changes of the heart caused by pressure and volume overload and by ventricular interaction. We investigated whether a novel echocardiographic index, i.e., the ratio of the atrial areas (RA/LA), would be useful for evaluating the clinical status of patients with pulmonary arterial hypertension (PAH) treated with intravenous epoprostenol. METHODS: We introduced epoprostenol therapy for seven PAH patients without severe tricuspid regurgitation. We evaluated clinical criteria indicative of prognosis, for example World Health Organization functional class (WHO-FC), brain natriuretic peptide (BNP) level, echocardiographic indices such as indexed RA area and RA/LA, and hemodynamics before and one year after intravenous epoprostenol therapy. RESULTS: There were significant improvements in both RA/LA (2.5 +/- 1.0, 1.3 +/- 0.4, P < 0.001) and indexed RA area (22.5 +/- 8.9, 14.5 +/- 5.8, P < 0.001). The improvement in RA/LA was more sensitive than that in indexed RA area (P < 0.01). Moreover, RA/LA was significantly correlated with WHO-FC (r = 0.50, P < 0.01) and BNP level (r = 0.82, P < 0.01). CONCLUSIONS: RA/LA is useful for evaluating the clinical status of patients with PAH treated with intravenous epoprostenol. PMID- 27277439 TI - Bladder neck evaluation by perineal ultrasound before and after reconstructive surgery for pelvic organ prolapse. AB - PURPOSE: To study the correlation between stress urinary incontinence (SUI) and the mobility and funneling of the bladder neck (BN) by observation of pre- and postoperative course by perineal ultrasound (PUS). METHODS: We investigated 123 cases that underwent reconstructive surgery for pelvic organ prolapse (POP). We prospectively checked bladder neck mobility (BNM) during the Valsalva maneuver and funneling of the BN at rest by PUS. We defined the width multiplied by the depth of the funnel-like profile of the BN as the funneling index (FI). We checked BNM, FI, and the presence of SUI just before the operation, and we checked the postoperative course of BNM and SUI. RESULTS: When BNM was >=10 mm before surgery, the odds ratio for accompanying SUI was 2.68 relative to BNM <10 mm (p = 0.031). When FI was >=150 before surgery, the odds ratio for accompanying SUI was 4.12 relative to FI <150 (p = 0.004). Although postoperative BNM values were significantly improved immediately after surgery, they gradually increased within 2 years. Among the cases with preoperative SUI, the recurrence rate was significantly higher in the patients whose FI was <150 (p = 0.019). CONCLUSIONS: Our results yielded by PUS suggested that larger BNM and FI values were the causative factors of SUI. PUS may be beneficial for selecting a suitable surgical procedure for POP, and it may also be helpful for assessing surgical efficacy. PMID- 27277441 TI - Portal gas in a diabetic patient under pharmacotherapy with an alpha-glucosidase inhibitor: report of a case with emphasis on US findings. AB - Portal gas is relatively rare, and its relation to ischemic bowel diseases has been emphasized. We report the case of a 56-year-old diabetic man under pharmacotherapy with an alpha-glucosidase inhibitor in which portal gas was incidentally detected by ultrasound (US). It showed multiple echo spots moving in the portal vein. Doppler signals confirmed them to be bidirectional and spiky, which immediately led to the diagnosis of portal gas. A change in oral antidiabetic drug caused the portal gas to disappear. We stress the usefulness of US and Doppler US for detecting and diagnosing portal gas. Although detailed analysis of a larger series of diabetic patients under this therapy is needed to draw a definitive conclusion, our observation merits attention. We also briefly review the literature. PMID- 27277442 TI - Severe subaortic stenosis that progressed over a 12-year period after cardiac surgery. AB - A 12-year-old girl who had undergone cardiac surgery for ventricular septal defect (VSD), atrial septal defect (ASD), and patent ductus arteriosus (PDA) in infancy was referred to our institution for fatigue and excessive sweating. Transthoracic and transesophageal echocardiographic studies revealed tunnel-type subaortic stenosis with aortic valvular stenosis, for which she underwent aortic valve replacement and myomectomy of left ventricular outflow tract. Progression of subaortic stenosis should be considered in patients with only mild aortic valve stenosis after previous cardiovascular surgery. Echocardiography contributed significantly to making the diagnosis and therapeutic decision in our patient. PMID- 27277443 TI - Atypical medullary carcinoma of the breast. PMID- 27277444 TI - Standard method for ultrasound evaluation of carotid artery lesions. PMID- 27277445 TI - Editor's Note. PMID- 27277446 TI - Scp3 expression in relation to the ovarian differentiation in the protogynous hermaphroditic ricefield eel Monopterus albus. AB - Synaptonemal complex protein 3 (Scp3), which is encoded by scp3, is a meiotic marker commonly used to trace the timing of gonadal differentiation in vertebrates. In the present study, the ricefield eel scp3 cDNA was cloned, and a fragment encoding amino acids 49 to 244 was overexpressed. The recombinant Scp3 polypeptide was purified and used to generate a rabbit anti-Scp3 polyclonal antiserum. In adult ricefield eels, scp3 mRNA was predominantly detected in the gonads and faintly detected in discrete brain areas. In the gonads, Scp3 immunoreactivities were shown to be localized to the germ cells, including meiotic primary growth oocytes, spermatocytes, and pre-meiotic spermatogonia. During early ovarian differentiation, immunoreactive Scp3 was not detected in the gonads of ricefield eels at 6 days post-hatching (dph) but was found to be abundantly localized in the cytoplasm of some oogonia at 7 dph, coinciding with the appearance of the ovarian cavity and ovarian differentiation. At 14 dph, strong Scp3 immunostaining was detected on one side of the nucleus with a distinct polarity in some germ cells, presumably at the leptotene stage. Consistent with these results, the expression of scp3 mRNA was faintly detected in the gonads of ricefield eels at 6 dph, increased at 8 dph, and then remained relatively high thereafter. Taken together, these results suggest that the appearance of immunoreactive Scp3 in oogonia could be a marker for early ovarian differentiation in ricefield eels. The translocation of the Scp3 protein from the cytoplasm to the nucleus in the oogonium of ricefield eels appears to be a controlled process that warrants further study. PMID- 27277447 TI - Open innovation in medical ultrasonics. PMID- 27277448 TI - Effect of fractionation on treatment outcome in local dual-frequency sonication and Dox-encapsulated nanomicelles. AB - PURPOSE: The goal of this study was to localize drug release from nanomicelles using dual-frequency sonication at low levels of acoustic intensity. METHODS: In this study, the antitumor effect of simultaneous dual-frequency sonication (28 kHz and 3 MHz) at low levels of acoustic intensity in combination with doxorubicin and micellar doxorubicin injection was assessed in a spontaneous model of breast adenocarcinoma in female Balb/c mice. Sixty-three tumor-bearing mice were randomly grouped into control, sham, dual-frequency sonication, doxorubicin injection with and without dual-frequency sonication, and micellar doxorubicin injection with and without dual-frequency sonication groups. RESULTS: The results of volume change relative to initial volume showed that in the micellar doxorubicin injection with sonication group, this parameter was significantly different from that of the control, sham, sonication, and doxorubicin injection groups (P < 0.05). In addition, the volume began to increase on the 15th day after the start of treatment, which is a good indication to repeat treatment; therefore, another group received an extra treatment on day 15. The animal life span in the micellar doxorubicin with sonication and repeated treatment groups was significantly higher than that in all the other experimental groups except for the micellar doxorubicin injection group (P < 0.05). CONCLUSION: It was concluded that dual-frequency sonication with micellar doxorubicin injection extends the life span relative to doxorubicin injection or dual-frequency sonication alone, and that repeating this treatment on day 15 decreases the rate of tumor growth significantly. PMID- 27277449 TI - JSUM ultrasound elastography practice guidelines: basics and terminology. AB - Ten years have passed since the first commercial equipment for elastography was released; since then clinical utility has been demonstrated. Nowadays, most manufacturers offer an elastography option. The most widely available commercial elastography methods are based on strain imaging, which uses external tissue compression and generates images of the resulting tissue strain. However, imaging methods differ slightly among manufacturers, which results in different image characteristics, for example, spatial and temporal resolution, and different recommended measurement conditions. In addition, many manufacturers have recently provided a shear wave-based method, providing stiffness images based on shear wave propagation speed. Each method of elastography is designed on the basis of assumptions of measurement conditions and tissue properties. Thus, we need to know the basic principles of elastography methods and the physics of tissue elastic properties to enable appropriate use of each piece of equipment and to obtain more precise diagnostic information from elastography. From this perspective, the basic section of this guideline aims to support practice of ultrasound elastography. PMID- 27277451 TI - JSUM ultrasound elastography practice guidelines: breast. AB - Ten years have passed since the first elastography application: Real-time Tissue ElastographyTM. Now there are several elastography applications in existence. The Quality Control Research Team of The Japan Association of Breast and Thyroid Sonology (JABTS) and the Breast Elasticity Imaging Terminology and Diagnostic Criteria Subcommittee, Terminology and Diagnostic Criteria Committee of the Japan Society of Ultrasonics in Medicine (JSUM) have advocated breast elastography classifications for exact knowledge and good clinical use. We suggest two types of classifications: the technical classification and the classification for interpretation. The technical classification has been created to use vibration energy and to make images, and also shows how to obtain a good elastic image. The classification for interpretation has been prepared on the basis of interpretation of evidence in this decade. Finally, we describe the character and specificity of each vender equipment. We expect the present guidelines to be useful for many physicians and examiners throughout the world. PMID- 27277450 TI - JSUM ultrasound elastography practice guidelines: liver. AB - In diffuse liver disease, it is extremely important to make an accurate diagnosis of liver fibrosis prior to determining indications for therapy or predicting treatment outcome and malignant potential. Although liver biopsy has long been the gold standard in the diagnosis of liver fibrosis, it is still an invasive method. In addition, the sampling error is an intrinsic problem of liver biopsy. Non-invasive serological methods for the diagnosis of liver fibrosis can be affected by factors unrelated to the liver. Recently, after the introduction of FibroScan, it became possible to measure liver fibrosis directly and non invasively by elastography, which has attracted attention as a non-invasive imaging diagnostic tool for liver fibrosis. In addition, real-time tissue elastography is currently being used to conduct clinical trials at many institutions. Moreover, virtual touch quantification enables the observation of liver stiffness at any location by simply observing B-mode images. Furthermore, the recently developed ShearWave elastography visualizes liver stiffness on a color map. Elastography is thought to be useful for all types of diffuse liver diseases. Because of its association with portal hypertension and liver carcinogenesis, elastography is expected to function as a novel prognostic tool for liver disease. Although various elastographic devices have been developed by multiple companies, each device has its own measurement principle, method, and outcome, creating confusion in clinical settings. Therefore, it is extremely important to understand the characteristics of each device in advance. The objective of this guideline, which describes the characteristics of each device based on the latest knowledge, is for all users to be able to make the correct diagnosis of hepatic fibrosis by ultrasound elastography. PMID- 27277452 TI - Frequency and implication of focal fatty sparing in segmental homogeneous fatty liver at ultrasound. AB - PURPOSE: The purpose of this study was to investigate whether focal fatty sparing arises from preexisting segmental homogeneous nonalcoholic fatty liver (NAFL). METHODS: Patients with various patterns of fatty liver were recruited from among 16,127 people, and 132 participants with segmental homogeneous NAFL were followed during the second year. All participants underwent ultrasonography. The sonographic findings in segmental homogeneous NAFL were analyzed. RESULTS: Of the 16,127 participants, 1,619 had fatty liver (10.0 %), and of these 1,568 had NAFL (9.72 %) and 51 had alcoholic fatty liver (0.31 %). Of the 1,568 patients with NAFL, 176 had homogeneous fatty liver with focal fatty sparing (11.2 %), 132 had segmental homogeneous fatty liver (8.42 %), and the rest had other patterns. At follow-up, of the 132 patients with segmental homogeneous fatty liver, 3 (2.3 %) were found to have a normal liver and 26 (19.7 %) diffuse homogeneous and heterogeneous fatty liver, and no focal fatty sparing was found (P < 0.001). CONCLUSIONS: Focal fatty sparing usually does not arise in preexisting segmental homogeneous NAFL. This implies that newly appearing nodular hypoechogenicity in segmental homogeneous fatty liver is more likely to be a true lesion rather than focal fatty sparing. PMID- 27277453 TI - Dorsal acoustic windows may ameliorate liver ultrasound in patients with chronic liver disease and meteorism/obesity/ascites. AB - PURPOSE: To identify dorsal acoustic windows (DAWs) for the study of the liver and to investigate whether they could improve the visualization of the liver in patients with chronic liver disease and ascites, meteorism, and/or obesity. METHODS: The study was based on a single ultrasound examination and divided into three successive stages. Firstly, we performed a preliminary study involving 10 cirrhotic patients to identify new DAWs. Inter-observer reproducibility of measurements obtained through the DAWs was then assessed in another 29 cirrhotic patients. Finally, in 50 patients with chronic hepatitis/cirrhosis, we employed the DAWs when ascites, meteorism or obesity hampered the conventional ultrasound examination. RESULTS: With patients sitting, we found three new DAWs, by the combined use of which it was possible to explore the liver, spleen, and their vascular structures, and which provided reproducible measurements. In the clinical setting, we found 11 of 50 patients in whom the addition of the new DAWs led to better results in terms of successful visualization/Doppler measurements for portal vein (ratio = 100 % vs 27 %, p = 0.001), hepatic artery (ratio = 90 % vs 27 %, p = 0.004), and hepatic veins (mean number = 2.4 +/- 0.2 vs 1.0 +/- 0.2, p = 0.01). Among these 11 patients, in one case the addition of DAWs led to visualization of hepatic focal lesions in the right lobe, not previously displayed through conventional ultrasound. CONCLUSION: These DAWs may be an additional tool that improves the accuracy of ultrasound examinations in patients with meteorism, ascites, or obesity. PMID- 27277454 TI - B-flow imaging of vascular structure for the diagnosis of liver tumor. AB - PURPOSE: B-flow is a non-Doppler-based technology for visualizing blood flow and has a high spatial resolution. The aim of this study is to evaluate the blood flow information of liver tumors using B-flow in comparison with color Doppler sonography (CDS). METHODS: Seventy-nine patients with 82 hepatic nodules were studied using B-flow and CDS. The study group included 45 HCC nodules, 23 liver metastasis nodules, four intrahepatic cholangiocarcinomas (ICC), and 13 hemangiomas. The visualized vascularity and morphological findings of the hepatic tumor vessel were evaluated. RESULTS: B-flow showed multiple vessels in 48 nodules (58.5 %) and a single vessel in 13 nodules (15.9 %). CDS showed multiple vessels in 44 nodules (53.7 %) and a single vessel in 23 nodules (28.0 %). Multivariate analysis showed basket pattern was significant for HCC (OR 49.263; p = 0.0002), and penetrating vessel was significant for liver metastasis or ICC (OR 14.545; p < 0.0001). CONCLUSION: B-flow detects hepatic tumor blood flow with sensitivity as high as that of CDS. Vascular structure information obtained using B-flow could be potentially used to diagnose liver tumors. PMID- 27277455 TI - Total and viable residual splenic volume measurement after partial splenic embolization by three-dimensional ultrasound. AB - PURPOSE: We prospectively evaluated the validity of total and viable residual splenic volume after partial splenic embolization (PSE) with three-dimensional (3D) ultrasound (US) measurement. METHODS: Twenty patients with splenomegaly were included. All splenic volumes were measured with transabdominal US using virtual organ computer-aided analysis (VOCAL). The viable residual splenic volume after PSE was estimated by using contrast-enhanced (CE) US with VOCAL. The agreement of the measurements from VOCAL and computed tomography (CT) was confirmed using interclass correlation coefficients (ICCs) and Bland-Altman plots. RESULTS: Mean volume was 503 +/- 250 ml for total spleen and 209 +/- 108 ml for viable residual volume. Regarding total volume, there was a high correlation and agreement (ICCs = 0.90) between 3D US and CT volumetry. Regarding viable residual volume, although there was a moderate correlation between 3D CEUS and CT volumetry, mean ICCs of 0.617 indicated poor agreement. With Bland-Altman plots, a narrow 95 % limit of agreement was observed among patients with a total volume under 1000 ml. CONCLUSION: The total splenic volume could be accurately estimated with 3D US. However, estimation of viable residual splenic volume should be limited in cases with total splenic volume under 1000 ml. PMID- 27277456 TI - Approach to improving sonographic visualization of elongated left lobe of the liver and its implications. AB - PURPOSE: To determine whether visualization of the elongated left lobe of the liver can be improved by distending the stomach with water and the implications of this technique. METHODS: Forty-three out of 87 patients with elongated left lobe of the liver found at abdominal CT were included in this study after obtaining informed consent. Their livers were examined using ultrasound before and after drinking water. The left lobe of the liver was scanned from the subxiphoid and left subcostal approaches, with the sound beam directed to the spleen and the left lobe of the liver neighboring or behind the stomach; the elongated left lobe of the liver overlying the spleen was detected by scanning from the 9th-11th intercostal approach of the left flank. RESULTS: The overall visualization of the elongated left lobe of the liver before and after filling the stomach with water was 4.7 % (2/43) and 100.0 % (43/43), respectively (P < 0.001); and the overall visualization of the spleen before and after filling the stomach with water was 4.7 % (2/43) and 100.0 % (43/43), respectively (P < 0.001). CONCLUSION: Distending the stomach with sufficient water can substantially improve visualization of elongated left lobe of the liver at ultrasound, potentially improving detection of tumors in the liver and preventing misdiagnosis. PMID- 27277457 TI - Ultrasound elastography for the differential diagnosis of nipple retraction. AB - PURPOSE: Nipple retraction is difficult to diagnose radiologically and extremely worrisome for patients. It occurs most commonly due to pathologies such as previous mastitis or an infiltrative malignancy. With this in mind, the goal of this study was to differentiate benign from malignant lesions of nipple retraction, using the differential characteristics of retroareolar area stiffness, observed by means of the new technological modality of ultrasound elastography (USE). MATERIALS AND METHODS: Nineteen unilateral nipple retraction cases, including five cases of mammary ductal carcinoma posteriorly infiltrated the areola, two cases of Paget disease, and 12 cases of mastitis, were investigated. Imaging findings [gray-scale ultrasound (US) and USE analyses of the breasts' nipple-areolar complex], pathological evaluation, and the results of 4 years of follow-up treatment were obtained. The recorded images were evaluated by two different radiologists, and all data were analyzed statistically. RESULTS: Statistical analysis showed that there was a strong correlation between the two radiologists' evaluations. The US images were not diagnostic for either the malignant or benign conditions. The correlation between the diagnosis using US and the final diagnosis was calculated as 0.436 (p = 0.006). However, the USE images were more informative since the correlation ratio between the USE results and the final diagnosis was found to be 0.723 (p < 0.001). While the area under the concentration curve (AUC) values that were used for the diagnostic determination of the US results were inconclusive at 0.274 (p < 0.021), the AUC values for USE were significant, with a diagnostic value of 0.866 for all cases (p < 0.01). CONCLUSION: The USE modality, which is not commonly used in routine practice, has the potential to solve the problem of differentiation of nipple retraction etiologies in the near future. PMID- 27277458 TI - Four-dimensional HDlive rendering image of fetal facial expression: a pictorial essay. AB - BACKGROUND: Our objective was to present our experience of fetal facial expressions reconstructed employing the four-dimensional (4D) HDlive rendering mode. METHODS: A total of 23 normal fetuses at 18-36 weeks' gestation were studied using the 4D HDlive rendering mode. RESULTS: The 4D HDlive rendering mode provided extraordinarily realistic features of the fetal face. In particular, blinking, mouthing, swallowing, yawning, tongue expulsion, and sucking were clearly noted. Moreover, various realistic fetal emotional expressions such as smiling-like and crying-like movements were recognized. The 4D HDlive rendered images of fetal facial expressions seem to be more readily discernible than those obtained by conventional 4D ultrasonography. CONCLUSION: Observation of facial expressions using the 4D HDlive rendering mode is considered to reflect the normal and abnormal neurological development of the fetus. Therefore, the 4D HDlive rendering mode may assist in evaluation of fetal brain function, and offer potential advantages relative to conventional 4D ultrasonography. PMID- 27277459 TI - Ultrasound evaluation of elbow fractures in children. AB - PURPOSE: Elbow fractures are a common pathology in any pediatric emergency unit. X-ray of the elbow is the standard diagnostic procedure. Previous studies have shown that fractures can also be visualized by ultrasound (US). The aim of our study was to evaluate the diagnostic accuracy of US in comparison to X-rays in diagnosing pediatric elbow fractures. METHODS: Sixty-seven patients aged 1-13 years with clinically suspected elbow fracture were first examined by US followed by standard two-plane radiographs. US examination was done with a 12-MHz linear probe from seven longitudinal positions across the distal humerus and additionally from longitudinal positions across the radial head and olecranon. The sonographic and radiological findings were compared in a contingency table, and sensitivity, specificity, and positive and negative predictive values of the US diagnostic procedure were calculated. RESULTS: With X-ray, we found 48 patients with an elbow fracture and 19 patients with no fracture. With US, we found 46 patients with an elbow fracture and 21 patients with no fracture. In comparison to X-ray diagnosis, we calculated for US diagnosis a sensitivity of 97.9 %, a specificity of 95 %, a negative predictive value of 95 %, and a positive predictive value of 97.9 %. CONCLUSION: Typical elbow fractures in children could also be visualized by US. A positive fat pad sign, in particular, serves as a strong indicator for elbow joint fractures and can be identified very sensitively by US. We confirm US as a valuable primary screening tool for elbow injuries in children. In the absence of US signs of fracture and in sonographically confirmed non-displaced fractures, standard X-rays are dispensable, thereby minimizing the X-ray burden in children without loss of diagnostic safety. PMID- 27277460 TI - Nonbacterial thrombotic endocarditis demonstrated by repeat echocardiography. AB - We report a case of nonbacterial thrombotic endocarditis (NBTE) in a patient with bladder cancer presenting with multiple cerebral infarctions. Initial transthoracic and transesophageal echocardiography did not show any abnormalities. However, repeat transthoracic and transesophageal echocardiography demonstrated a vegetation on the anterior leaflet of the mitral valve with mild mitral regurgitation and no evidence of leaflet destruction. Persistent high grade fevers and leukocytosis were observed. The patient was suspected to have infective endocarditis. However, abdominal ultrasound and computed tomography scan revealed multiple metastatic masses, and serial blood cultures were negative. The patient was ultimately diagnosed with NBTE associated with multiple metastases of bladder cancer. This case suggests that even if echocardiography does not initially demonstrate any abnormalities in patients with embolism, it must be repeated at the recurrence of embolism, and that even if clinical signs of infection are documented, NBTE should be suspected in any cancer patient with thromboembolic events. PMID- 27277461 TI - Rare sonographic finding of osteogenesis imperfecta type 2: fluid retention in the subarachnoid space. AB - Osteogenesis imperfecta (OI) type 2 is the most severe form of this osteogenetic disorder. A 26-year-old woman was referred to our hospital for suspected fetal hydrocephalus at 26 weeks' gestation. Detailed ultrasonographic examination revealed fluid retention in the subarachnoid space. The fetal head was expanded, and the skull bone was easily deformed by the pressure of the ultrasound probe. Pleural effusion and ascites were noted, and the upper and lower extremities were extremely shortened and deformed. On helical 3D-CT, the skull bones could not be imaged, and multiple rib fractures and deformed long bones were suspected. Based on these findings, the fetus was diagnosed with OI type 2, and it was explained to the patient and her family that this disease was fatal. Due to non-reassuring fetal status at 28 weeks, induced breech delivery resulted in a stillborn infant. The head of the infant was soft, and the upper and lower extremities were extremely shortened. Post-mortem radiography confirmed the presence of deformed long bones and ribs with multiple fractures, while the skull bones could not be imaged. Detailed ultrasound observation may detect cerebrospinal fluid retention in the subarachnoid space, a finding that may be associated with the membranous skull bones of this osteogenetic disorder. PMID- 27277462 TI - Early ultrasonographic evaluation of tumor thrombus level during sunitinib therapy for renal cell carcinoma. AB - A 72-year-old man presenting with a 14-cm left renal mass, an inferior vena cava (IVC) tumor thrombus, and pulmonary metastases underwent renal mass biopsy that revealed clear cell renal cell carcinoma. Because of metastases and the extent of the tumor thrombus, sunitinib was administered, which resulted in a marked reduction in the tumor thrombus (from level III to level II after 11 weeks of treatment). Ultrasonography, preceding computed tomography, showed a slight shrinkage of the tumor thrombus level in the first 2 weeks. Therefore, ultrasound may be advantageous to monitor the IVC tumor thrombus level during the early phase of targeted therapy. PMID- 27277464 TI - Sonography of multifocal hydatidosis involving lung and liver in a female child. AB - Hydatid disease, caused by Echinococcus granulosus, is a zoonotic infection encountered worldwide. Though involvement of the liver and lungs is quite common, pelvic involvement is rarely reported, with the incidence being 0.2-2.2 %. Ovarian and broad ligament hydatids are rare entities and are usually seen after rupture of a hepatic hydatid cyst. These cysts are usually asymptomatic, and a high index of clinical suspicion coupled with unequivocal imaging findings is required to make an accurate and timely diagnosis. We present a case of multifocal hydatid disease in a female child involving the lungs and liver and provide an account of the quintessential radiological findings. PMID- 27277463 TI - Utility of ultrasound in the diagnosis of chronic worsened gout. AB - Ultrasound (US) may be used to diagnose chronic worsened gout. US confirmed the clinical evidence of tophaceous deposits in the left elbow of a 75-year-old man; it also identified crystalline materials on the cartilage surface of the second metacarpophalangeal joint of the left hand. US may be helpful to detect signs of deposition of monosodium urate crystals in periarticular and intra-articular joints of patients with clinically suspected chronic worsened gout. PMID- 27277465 TI - Ultrasound-guided arthroscope insertion and decompression of a supraspinous fossa cyst. AB - A cyst arising in the scapular supraspinous fossa may cause shoulder pain; subsequently, enlargement of the cyst may result in severe compression of the adjacent suprascapular nerve, leading to muscle weakness and sensory disorder. Decompression of the nerve through cyst removal is effective in resolving these symptoms. However, treatment can also be performed less invasively through arthroscopy. Insertion of an arthroscope without visual guidance could cause tissue damage and, consequently, would become an invasive procedure itself. The use of ultrasonography to guide the scope to the cyst decreases the invasiveness of the procedure. Here, we present the case of a patient with a cyst arising in the scapular supraspinous fossa, in whom we could relatively readily and safely observe the cyst by advancing an arthroscope under ultrasonographic guidance. The suprascapular nerve was decompressed via cyst removal. PMID- 27277466 TI - Primary cardiac lymphoma diagnosed by endomyocardial biopsy using transthoracic echocardiography in the substernal window. AB - We report a case of a 56-year-old man with a cardiac tumor, which grew and spread rapidly in the right heart. Using transthoracic echocardiography (TTE) in the substernal window, a transvenous biopsy of the tumor was performed safely. The tissue diagnosis revealed a diffuse large B cell lymphoma. After undergoing chemotherapy, the tumor was completely cured and the patient continues to be in good health. A biopsy using TTE in the substernal window may be a useful method to diagnose right-sided extensive tumors. PMID- 27277468 TI - Ultrasonographic findings: an unusual case of secondary leiomyosarcoma after radiotherapy for breast cancer. PMID- 27277467 TI - Atherosclerotic splenic artery aneurysm in a decompensated cirrhotic patient. AB - Splenic artery aneurysm is a rare condition with potential lethal complications. If associated with severe diseases, the diagnosis and management may be challenging. Usually, ultrasound examination is the first step in the diagnosis, and the specific ultrasound features suggest the diagnosis. When combined with contrast-enhanced ultrasound examination, the accuracy of ultrasound increases and can therefore rule out some severe complications. We present the case of a patient hospitalized with decompensated cirrhosis in whom the ultrasound examination revealed the presence of a high-risk splenic artery aneurysm. However, the treatment decisions were profoundly influenced by the liver disease complications. PMID- 27277469 TI - HDlive rendering image at 6 weeks of gestation. PMID- 27277470 TI - Ultrasonographic diagnostic criteria for pancreatic cancer. PMID- 27277471 TI - Editor's Note. PMID- 27277473 TI - Wellens' syndrome. PMID- 27277474 TI - Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance. AB - BACKGROUND: Guizhi-Shaoyao-Zhimu decoction (GSZD) has been extensively used for rheumatoid arthritis (RA) therapy. Marked therapeutic efficacy of GSZD acting on RA has been demonstrated in several long-term clinical trials without any significant side effects. However, its pharmacological mechanisms remain unclear due to a lack of appropriate scientific methodology. METHODS: GSZD's mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation. RESULTS: A total of 77 putative targets were identified for 165 assessed chemical components of GSZD. After calculating the topological features of the nodes and edges in the created drug-target network, we identified a candidate GSZD-targeted signal axis that contained interactions between two putative GSZD targets [histone deacetylase 1 (HDAC1) and heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1)] and three known RA-related targets [NFKB2; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB); and tumor necrosis factor-alpha (TNF-alpha)]. This signal axis could connect different functional modules that are significantly associated with various RA-related signaling pathways, including T/B cell receptor, Toll-like receptor, NF-kappa B and TNF pathways, as well as osteoclast differentiation. Furthermore, the therapeutic effects and putative molecular mechanisms of GSZD's actions on RA were experimentally validated in vitro and in vivo. CONCLUSIONS: GSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1-HSP90AA1-NFKB2-IKBKB-TNF-alpha signaling axis. PMID- 27277475 TI - The 5-HTTLPR and BDNF polymorphisms moderate the association between uncinate fasciculus connectivity and antidepressants treatment response in major depression. AB - Symptom improvement in depression due to antidepressant treatment is highly variable and clinically unpredictable. Linking neuronal connectivity and genetic risk factors in predicting antidepressant response has clinical implications. Our investigation assessed whether indices of white matter integrity, serotonin transporter-linked polymorphism (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) val66met polymorphism predicted magnitude of depression symptom change following antidepressant treatment. Fractional anisotropy (FA) was used as an indicator of white matter integrity and was assessed in the uncinate fasciculus and superior longitudinal fasciculus using tract-based spatial statistics (TBSS) and probabilistic tractography. Forty-six medication-free patients with major depressive disorder participated in a diffusion tensor imaging scan prior to completing an 8-week treatment regime with citalopram or quetiapine XR. Indexed improvements in Hamilton Depression Rating Scale score from baseline to 8-week endpoint were used as an indicator of depression improvement. Carriers of the BDNF met allele exhibited lower FA values in the left uncinate fasciculus relative to val/val individuals [F(1, 40) = 7.314, p = 0.009]. Probabilistic tractography identified that higher FA in the left uncinate fasciculus predicted percent change in depression severity, with BDNF moderating this association [F(3, 30) = 3.923, p = 0.018]. An interaction between FA in the right uncinate fasciculus and 5-HTTLPR also predicted percent change in depression severity [F(5, 25) = 5.315, p = 0.002]. Uncorrected TBSS results revealed significantly higher FA in hippocampal portions of the cingulum bundle in responders compared to non-responders (p = 0.016). The predictive value of prefrontal and amygdala/hippocampal WM connectivity on antidepressant treatment response may be influenced by 5-HTTLPR and BDNF polymorphisms in MDD. PMID- 27277479 TI - The contributions of ultrasound to medicine. PMID- 27277478 TI - Disordered eating behavior, health and motives to exercise in young men: cross sectional population-based MOPO study. AB - BACKGROUND: Being overweight is an increasing problem among young people, among whom disordered eating behavior is linked with weight problems as well as unhealthy weight control. The aim of the present study was to investigate whether health factors and motives to exercise differ in young men by the type of disordered eating behavior. METHODS: The population-based, cross-sectional MOPO study consisted of 2,096 young Finnish men (mean age 17.9, SD 0.7) attending compulsory call-ups for military service in the Oulu area in 2010, 2011, and 2013. They responded to a questionnaire that included two subscales of the Eating Disorder Inventory-3 indicating drive for thinness and bulimic behavior and questions on health, physical activity, and motives to exercise. The association between disordered eating behavior and related factors was analyzed by binary logistic regression. RESULTS: Altogether, 6.9 % (n = 145) of the men had symptoms of disordered eating, i.e., 5.4 % had a drive for thinness (n = 114) and 3.7 % had bulimic behavior (n = 77). Drive for thinness was associated with a perception of being overweight (OR 3.7; 95 % CI 2.2-6.1), poor self-rated health (2.3; 1.2-4.4), more leisure sitting time (1.1; 1.0-1.2), and body-related exercise motives (body acceptance: 3.0; 1.7-5.2; weight loss: 2.5; 1.4-4.4). Bulimic behavior was positively associated with poor self-rated health (2.6; 1.1 5.8) and several motives to exercise, i.e., due to another person's suggestion (2.8; 1.6-4.8), competitive sports (2.1; 1.2-3.7), body acceptance (2.1; 1.1 3.9), and weight loss (1.9; 1.1-3.3), but inversely associated with health/fitness-related exercise motives (health promotion: 0.3; 0.1-0.5; muscular strength or physical performance: 0.5; 0.2-0.9). CONCLUSIONS: In young men, disordered eating behavior was associated with being overweight, having poor self rated health, and having a greater amount of leisure sitting time as well as non health-related motives to exercise. In order to recognize those at risk for disordered eating behavior, evaluating these factors could be beneficial. PMID- 27277480 TI - Quantitative evaluation of diagnostic information around the contours in ultrasound images. AB - PURPOSE: To develop a new contour extraction method for identifying abnormal tissue. METHODS: We combined two techniques: logarithmic K distribution of a scattering model (method 1) and regional discrimination using the characteristics of local ultrasound images (method 2) into an integrated method (method 3) that provides accurate contours, which are essential for quantitizing border information. RESULTS: The diagnostic tissue information around the border of an image can be characterized by its shape and texture statistics. The degrees of circularity and irregularity and the depth-width ratio were calculated for the extracted contours of breast tumors. In addition, gradients, separability, and variance between the two regions along the contour and the area and variance of the internal echoes, were calculated as indices of diagnostic criteria of breast tumors. The quantitized indices were able to discriminate among cysts, fibroadenomas, and cancer. CONCLUSION: In many ultrasound images of breast tumors, the combined techniques, the variance ratio of the logarithmic K distribution to the logarithmic Rayleigh distribution and the multilevel technique with local image information can effectively extract abnormal tissue contours. PMID- 27277477 TI - Correlation between prostate volume and single nucleotide polymorphisms implicated in the steroid pathway. AB - OBJECTIVES: A few preliminary studies have suggested a link between some genetics variants and benign prostatic hyperplasia (BPH). Our goal was to study the link between a set of single nucleotide polymorphisms (SNPs) implicated in the steroid pathway and accurate measurement of prostate volume in a cohort of men who underwent radical prostatectomy. METHODS: Clinical and pathological data including prostate weight were obtained from 611 Caucasian patients with small volume, localized prostate cancer treated by radical prostatectomy. Patients were genotyped for 90 SNPs located inside or nearby genes implicated in the steroid pathway (Sequenom iPLEX). Correlation between prostate weight and genotypes from each SNP was studied by analysis of covariance, adjusted on age and tumor stage. A Bonferroni correction was applied, and the SNPs implicated were then incorporated in a multivariable model. RESULTS AND LIMITATIONS: Seven SNPs located in or nearby genes implicated in steroid hormone metabolism were significantly associated with prostate volume: HSD17B2 (rs1119933), ESR2 (rs8006145), SULT2B1 (rs279451), NQO1 (rs2917670), ESR1 (rs1569788), GSTP1 (rs1138272), and CYP19A1 (rs17523880). Significant association was maintained after multivariate analysis for four SNPs, indicating their independent association with prostate volume. The power of the association of each SNP with prostate volume was comparable to the effect of age. The strongest associations were found with variants in ESR1, ESR2, HSD17B2, and CYP19A1 genes, indicating a potential role of the estrogen signaling pathway in genesis of BPH. CONCLUSIONS: Our results are in favor of an implication of estrogen biotransformation and signaling pathways in the pathophysiology of BPH. PMID- 27277481 TI - Effects of sublingual nitroglycerin on working conditions of the heart and arterial system: analysis using wave intensity. AB - PURPOSE: The effects of nitroglycerin (NTG) on the vascular system are well known. However, the effects of NTG on the heart are still obscure, because these effects are modified by those on the vascular system, and vice versa. Therefore, to evaluate the hemodynamic effects of NTG, it is important to understand the interaction between the heart and the vascular system. Wave intensity (WI) is a new hemodynamic index that provides information about working conditions of the heart interacting with the arterial system. The purpose of this study was to evaluate the interactive effects of NTG on the cardiovascular system in normal subjects using wave intensity. METHODS: We simultaneously measured carotid arterial blood flow velocity and diameter change using a specially designed ultrasonic system, and calculated the WI and the stiffness parameter beta. Measurements were made in 13 normal subjects (9 men and 4 women, aged 47 +/- 10 years) in the supine position before and after sublingual NTG. RESULTS: The maximum value of WI (W 1) and the mid-systolic expansion wave (X) increased (W 1 from 9.1 +/- 4.3 to 12.3 +/- 5.5 * 10(3) mmHg m/s(3), P < 0.001; X from 105 +/- 185 to 345 +/- 370 mmHg m/s(3), P < 0.05). beta increased (from 10.5 +/- 3.8 to 14.1 +/- 3.8, P < 0.001). The pressure contours changed considerably. CONCLUSIONS: NTG increased W 1 and the mid-systolic expansion wave, which suggests enhanced cardiac power during the initial ejection and mid-systolic unloading. These results are new findings about the effects of NTG that can be added to the widely known late systolic unloading and preload reduction. NTG also increased arterial stiffness, which reduces the Windkessel function. By using an echo-Doppler system, WI can be obtained noninvasively. WI has the clinical potential to provide quantitative and detailed information about working conditions of the heart interacting with the arterial system. PMID- 27277482 TI - Diagnosis of follicular carcinoma of the thyroid: role of sonography in preoperative diagnosis of follicular nodules. AB - The purpose of this study was to evaluate sonographic examination, as well as other clinical tests, for clarifying the parameters for predicting follicular carcinoma in follicular nodules of the thyroid. Nine hundred and ten consecutive patients with follicular nodules were pathologically classified as having follicular carcinoma (109 patients) or benign tumor (811 patients). Benign tumors included follicular adenoma (237 patients) and adenomatous thyroid nodules (574 patients). A case-control study was performed for follicular carcinomas and benign tumors. "Thyroglobulin 1000 ng/ml?", "cytology class 3?", and a "solid pattern", "low-echoic level of internal echo", and "jagged borders" of follicular carcinomas were found to be significantly higher than those of benign tumors. The sensitivities of a solid pattern (79.8%) and a low-echoic level (75.2%) were found to be relatively higher than those of other features and findings. The specificities of thyroglobulin 1000 ng/ml?(84.0%), cytology class 3?, and jagged borders (86.2%) were found to be relatively higher than those of other features and findings. We concluded that thyroglobulin 1000 ng/ml? and cytology class 3? in clinical features, and a solid pattern, low-echoic level, and jagged borders on sonography, indicated an increased risk of follicular carcinoma of the thyroid in follicular nodules. PMID- 27277483 TI - Trial of a quantitative method for evaluating hemangioma of the liver and hepatocellular carcinoma using a radio-frequency signal. AB - PURPOSE: In recent years, advances in ultrasonographic techniques have allowed the detection of even small hepatocellular carcinomas. However, many cases do not show distinctive ultrasonographic features. A quantitative ultrasonographic procedure for making the diagnosis would therefore be desirable. It is recognized that radio-frequency (RF) signals from hepatic tumors conform to the K distribution. The K distribution is used for the characterization of the statistical properties of backscattering signals from heterogeneous regions. In this study, RF signals were acquired from hemangioma of the liver (hemangioma) and hepatocellular carcinoma (HCC), and parameters of the K distribution, i.e., phi (the mean square of the amplitude of RF signals) and alpha (the number of effective scatterers), were calculated for the quantitative ultrasonographic evaluation of hepatic tumors. METHODS: This study included 10 nodules of 10 patients with hemangioma and 27 nodules of 24 patients with HCC. The A-mode RF signals passing through the hepatic tumors were acquired with an Aloka SSD-1000 ultrasound system, and measurement units comprising 279 points were set on the RF signals corresponding to the tumor lesion. The parameters of the K distribution that were most consistent with the histogram were calculated and assessed. RESULTS: With regard to phi, the values were high in hemangioma, and there was a significant (P < 0.05) difference in the phi value between hemangioma and HCC. On the other hand, there was no significant difference in the alpha value between hemangioma and HCC. CONCLUSION: The alpha values of hemangioma were equivalent to those of HCC, while the phi values for hemangioma were higher than those for HCC. It was deduced from these observations that a situation in which an electron beam is likely to scatter exists in the tumor. This is also consistent with the pathological findings reported from previous studies. The use of these parameters is expected to allow quantitative ultrasonographic evaluation of hepatic tumors. PMID- 27277484 TI - Detection of hepatocellular carcinoma capsule by contrast-enhanced ultrasound using Levovist: correlations with pathological findings. AB - PURPOSE: To determine the most appropriate therapy for each hepatocellular carcinoma (HCC) nodule, it is important to ascertain whether the tumor has a capsule. The aim of this study was to investigate the diagnostic potential of contrast-enhanced ultrasound (CEUS) in HCC capsule detection by comparing ultrasound findings with histological results from operative specimens. METHODS: Thirty-six HCC nodules (all smaller than 5 cm) from 36 patients who had undergone hepatectomy were examined by CEUS using Levovist with agent detection imaging. The vascular phase images and time course changes of HCC were observed after a bolus injection of Levovist. We classified the appearance of the tumor artery, tumor enhancement, and washout into several patterns. We grouped HCCs into encapsulated or nonencapsulated on the basis of the histology of the operative specimens, taking into account the effectiveness of transcatheter arterial chemoembolization. Ultrasound and pathological findings were compared to assess the ability of CEUS to detect HCC capsules. RESULTS: During the arterial phase, 12 (80.0%) encapsulated and 3 (14.3%) nonencapsulated HCC nodules showed a surrounding artery with branches pattern (P < 0.0001). The sensitivity, specificity, and accuracy of this pattern for HCC capsule detection were 80%, 86%, and 83%, respectively. A branching artery was found in 15 (71.4%) nonencapsulated but in only 3 (20.0%) encapsulated HCC nodules (P < 0.01). The sensitivity, specificity, and accuracy of this branching artery pattern for confirming the absence of a capsule in HCC nodules were 71%, 80%, and 75%, respectively. Almost all HCC nodules showed strong-moderate or weak enhancement and strong-moderate or mild washout. Neither enhancement nor washout pattern correlated with the presence of a capsule. CONCLUSION: The arterial phase of CEUS is very useful for detection of HCC capsules and therefore facilitates selection of the most appropriate treatment method for HCC. PMID- 27277485 TI - Current state and effectiveness of abdominal ultrasonography in complete medical screening. AB - PURPOSE: The current state and effectiveness of abdominal ultrasonography (US) were investigated by reviewing statistical data for US of the kidney as part of complete medical screenings conducted at our institution between April 1994 and March 2004. METHODS: Among 4339 individuals with US findings, computed tomography (CT) was performed on 129 individuals at our institution. Among these individuals, US findings and CT diagnoses were compared and analyzed. RESULTS: US findings indicated renal tumors in 73 of the 129 subjects, and the breakdown of CT diagnoses for these 73 individuals was as follows: no lesion, n = 45 (61.6%); simple renal cyst, n = 13 (17.8%); complicated renal cyst, n = 5 (6.8%); suspected malignant tumor, n = 5 (6.8%); renal angiomyolipoma, n = 2 (2.7%); pelvic dilatation, n = 1 (1.4%); granuloma, n = 1 (1.4%); teratoma, n = 1 (1.4%). Magnetic resonance imaging (MRI) was performed on 4 of the 5 subjects with suspected malignant tumor, and surgery was performed in all 4 cases with suspected kidney cancer. Kidney cancer was histopathologically confirmed in 2 patients, resulting in a detection rate of 0.046% for kidney cancer by US as part of a complete medical screening. In the 2 patients with kidney cancer, differentiating cystic renal cell cancer from a renal cyst was not possible based on US findings alone in 1 patient, and no thorough examinations were performed in the 3 years leading up to surgery. CONCLUSIONS: These results suggest that additional US and thorough examinations are necessary if a lesion cannot be confirmed as a simple renal cyst on initial US. Furthermore, to improve the skill levels of healthcare professionals who perform and interpret US, a feedback system should be established where data related to complete medical screenings are available to the personnel involved. PMID- 27277486 TI - Three-dimensional ultrasonography of hydrocephalus. AB - We examined two infants with hydrocephalus using three-dimensional (3-D) ultrasonography. One infant had congenital hydrocephalus with a ventriculoperitoneal shunt. On 2-D ultrasonography, the shunt tube was shown only as "a point." However, on 3-D ultrasonography, we could easily see the three dimensional position of the shunt tube, which was situated in the lateral ventricle. The other patient had hydrocephalus associated with an arachnoid cyst. We could understand the complex shape of the cyst and distinguish it from the third ventricle using 3-D ultrasonography. Thus, 3-D ultrasonography imaging is more useful than 2-D ultrasonography imaging in evaluating hydrocephalus. PMID- 27277487 TI - Multiple metastases from a meningeal hemangiopericytoma associated with severe hypoglycemia. AB - Hemangiopericytomas are rare vascular tumors that may be associated with profound hypoglycemia. We present correlative imaging findings for a 57-year-old woman who had multiple abdominal and muscular metastases with severe hypoglycemia 11 years after resection of meningeal hemangiopericytoma. The metastases were well-defined masses containing solid and cystic components, and they were extremely hypervascular in the solid component. Those characteristics on imaging associated with hypoglycemia and the past history of meningeal hemangiopericytoma may suggest the diagnosis and be helpful in differentiating the mass from other vascular tumors. Color and power Doppler ultrasound may play a valuable role in characterizing and diagnosing metastasis from hemangiopericytoma. A delay of several years between diagnosis of the primary hemangiopericytoma and the manifestation of metastasis appears to be a special feature of hemangiopericytoma. PMID- 27277488 TI - Hepatic angiomyolipoma: identification of an efferent vessel as a hepatic vein by contrast-enhanced harmonic sonography. AB - Two cases of hepatic angiomyolipoma were studied by contrast-enhanced harmonic sonography. The special tumor hemodynamics, namely the efferent blood flow of the hepatic angiomyolipoma draining into the hepatic vein, were clearly shown on harmonic imaging, and they corresponded well with those seen on angiography and computed tomography during angiography. Benign hepatic tumors were diagnosed preoperatively in both cases according to the hemodynamic findings. Hepatic angiomyolipoma was finally identified histologically. The special tumor hemodynamics might be one of the important characteristics of hepatic angiomyolipoma. Contrast-enhanced harmonic sonography is useful for the detection of special tumor hemodynamics and may facilitate the differential diagnosis from other hepatic tumors, especially malignant liver tumors. PMID- 27277489 TI - Hemodynamic and morphologic changes of peripheral hepatic vasculature in chronic liver disease: a preliminary study by contrast-enhanced coded phase-inversion harmonic sonography. AB - To investigate whether observing the morphology of the peripheral hepatic vasculature and the hemodynamics of microbubble arrival time in these vessels can provide useful information for the diagnosis of liver disease, Five normal volunteers and 16 patients were studied by contrast-enhanced coded phase inversion harmonic sonography. Vessel images of the peripheral vessels were observed in real time after intravenous injection of Levovist. The time when the microbubbles appeared in the peripheral vessels was measured. Three patterns of morphologic change of the peripheral hepatic vasculature were seen, marked, slight, and no abnormal changes. The microbubble arrival times at the peripheral vessels were all shorter in patients with cirrhosis than chronic hepatitis or normal subjects. Marked, slight, and no abnormal morphologic changes of the peripheral hepatic vasculature in patients with liver cirrhosis were found in five, one and zero of the six patients, respectively. Those patients with chronic hepatitis, were found in one, six and three of the ten patients, respectively. There was a significant difference among the different groups (P < 0.001). Evaluating the hemodynamics and morphology by contrast-enhanced coded pulse inversion harmonic sonography may offer useful information in the diagnosis of liver disease. PMID- 27277491 TI - When ultrasound fails to demonstrate a palpable abdominal mass. PMID- 27277490 TI - Imaging findings of biliary hamartomas (von Meyenburg complexes). AB - To evaluate the imaging findings of biliary hamartomas (von Meyenburg complexes, vMCs) and discuss their differential diagnosis from other related diseases, imaging findings of biliary hamartomas on ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and hepatobiliary scintigraphy were prospectively analyzed in six patients. On ultrasound images, five of the six cases showed multiple small hyper- and hypoechoic lesions with comet-tail echoes, especially when magnified using the zoom function. In all six cases, multiple tiny hypodense lesions less than 10 mm in diameter were scattered throughout the liver with no enhancement on CT. These tiny lesions were demonstrated to be hyper and hypointense on T2- and TI-weighted images, respectively, in three patients who underwent MRI examinations. MRCP was performed in two patients, and it clearly showed multiple tiny round and irregular-shaped hyperintense lesions. MRCP and hepatobiliary scintigraphy showed normal appearances of intra- and extrahepatic bile ducts in two and one patients, respectively. Imaging modalities are useful in the diagnosis and differential diagnosis of vMCs. A correct diagnosis might be obtained when typical imaging findings present even without histological confirmation. PMID- 27277492 TI - Criteria for the diagnosis of developmental dysplasia of the hip joint (proposal). PMID- 27277495 TI - Hospital-Based Outpatient Direct Access to Physical Therapist Services: Current Status in Wisconsin. AB - BACKGROUND: Direct access to physical therapist services is available in all 50 states, with reported benefits including reduced health care costs, enhanced patient satisfaction, and no apparent compromised patient safety. Despite the benefits and legality of direct access, few data exist regarding the degree of model adoption, implementation, and utilization. OBJECTIVES: The purposes of the study were: (1) to investigate the extent of implementation and utilization of direct access to outpatient physical therapist services in Wisconsin hospitals and medical centers, (2) to identify barriers to and facilitators for the provisioning of such services, and (3) to identify potential differences between facilities that do and do not provide direct access services. DESIGN: A descriptive survey was conducted. METHODS: Eighty-nine survey questionnaires were distributed via email to the directors of rehabilitation services at Wisconsin hospitals and medical centers. The survey investigated facility adoption of the direct access model, challenges to and resources utilized during model implementation, and current barriers affecting model utilization. RESULTS: Forty seven (52.8%) of the 89 survey questionnaires were completed and returned. Forty two percent of the survey respondents (20 of 47) reported that their facility offered direct access to physical therapist services, but fewer than 10% of patients were seen via direct access at 95% of the facilities offering such services. The most frequently reported obstacles to model implementation and utilization were lack of health care provider, administrator, and patient knowledge of direct access; its legality in Wisconsin; and physical therapists' differential diagnosis and medical screening abilities. LIMITATIONS: Potential respondent bias and limited generalizability of the results are limitations of the study. These findings apply to hospitals and medical centers located in Wisconsin, not to facilities located in other geographic regions. CONCLUSIONS: Respondents representing direct access organizations reported more timely access to physical therapist services, enhanced patient satisfaction, decreased organizational health care costs, and improved efficiency of resource utilization as benefits of model implementation. For organizations without direct access, not being an organizational priority, concerns from referral sources, and concerns that the physician-patient relationship would be negatively affected were noted as obstacles to model adoption. PMID- 27277494 TI - Identifying Multimodal Intermediate Phenotypes Between Genetic Risk Factors and Disease Status in Alzheimer's Disease. AB - Neuroimaging genetics has attracted growing attention and interest, which is thought to be a powerful strategy to examine the influence of genetic variants (i.e., single nucleotide polymorphisms (SNPs)) on structures or functions of human brain. In recent studies, univariate or multivariate regression analysis methods are typically used to capture the effective associations between genetic variants and quantitative traits (QTs) such as brain imaging phenotypes. The identified imaging QTs, although associated with certain genetic markers, may not be all disease specific. A useful, but underexplored, scenario could be to discover only those QTs associated with both genetic markers and disease status for revealing the chain from genotype to phenotype to symptom. In addition, multimodal brain imaging phenotypes are extracted from different perspectives and imaging markers consistently showing up in multimodalities may provide more insights for mechanistic understanding of diseases (i.e., Alzheimer's disease (AD)). In this work, we propose a general framework to exploit multi-modal brain imaging phenotypes as intermediate traits that bridge genetic risk factors and multi-class disease status. We applied our proposed method to explore the relation between the well-known AD risk SNP APOE rs429358 and three baseline brain imaging modalities (i.e., structural magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and F-18 florbetapir PET scans amyloid imaging (AV45)) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The empirical results demonstrate that our proposed method not only helps improve the performances of imaging genetic associations, but also discovers robust and consistent regions of interests (ROIs) across multi modalities to guide the disease-induced interpretation. PMID- 27277496 TI - The 2015 Nepal Earthquake(s): Lessons Learned From the Disability and Rehabilitation Sector's Preparation for, and Response to, Natural Disasters. AB - The frequency of natural disasters appears to be mounting at an alarming rate, and the degree to which people are surviving such traumatic events also is increasing. Postdisaster survival often triggers increases in population and individual disability-related outcomes in the form of impairments, activity limitations, and participation restrictions, all of which have an important impact on the individual, his or her family, and their community. The increase in postdisaster disability-related outcomes has provided a rationale for the increased role of the disability and rehabilitation sector's involvement in emergency response, including physical therapists. A recent major earthquake that has drawn the world's attention occurred in the spring of 2015 in Nepal. The response of the local and international communities was large and significant, and although the collection of complex health and disability issues have yet to be fully resolved, there has been a series of important lessons learned from the 2015 Nepal earthquake(s). This perspective article outlines lessons learned from Nepal that can be applied to future disasters to reduce overall disability related outcomes and more fully integrate rehabilitation in preparation and planning. First, information is presented on disasters in general, and then information is presented that focuses on the earthquake(s) in Nepal. Next, field experience in Nepal before, during, and after the earthquake is described, and actions that can and should be adopted prior to disasters as part of disability preparedness planning are examined. Then, the emerging roles of rehabilitation providers such as physical therapists during the immediate and postdisaster recovery phases are discussed. Finally, approaches are suggested that can be adopted to "build back better" for, and with, people with disabilities in postdisaster settings such as Nepal. PMID- 27277497 TI - Use of Perturbation-Based Gait Training in a Virtual Environment to Address Mediolateral Instability in an Individual With Unilateral Transfemoral Amputation. AB - BACKGROUND AND PURPOSE: Roughly 50% of individuals with lower limb amputation report a fear of falling and fall at least once a year. Perturbation-based gait training and the use of virtual environments have been shown independently to be effective at improving walking stability in patient populations. An intervention was developed combining the strengths of the 2 paradigms utilizing continuous, walking surface angle oscillations within a virtual environment. This case report describes walking function and mediolateral stability outcomes of an individual with a unilateral transfemoral amputation following a novel perturbation-based gait training intervention in a virtual environment. CASE DESCRIPTION: The patient was a 43-year-old male veteran who underwent a right transfemoral amputation 7+ years previously as a result of a traumatic blast injury. He used a microprocessor-controlled knee and an energy storage and return foot. OUTCOMES: Following the intervention, multiple measures indicated improved function and stability, including faster self-selected walking speed and reduced functional stepping time, mean step width, and step width variability. These changes were seen during normal level walking and mediolateral visual field or platform perturbations. In addition, benefits were retained at least 5 weeks after the final training session. DISCUSSION: The perturbation-based gait training program in the virtual environment resulted in the patient's improved walking function and mediolateral stability. Although the patient had completed intensive rehabilitation following injury and was fully independent, the intervention still induced notable improvements to mediolateral stability. Thus, perturbation-based gait training in challenging simulated environments shows promise for improving walking stability and may be beneficial when integrated into a rehabilitation program. PMID- 27277498 TI - Diet may influence the oral microbiome composition in cats. AB - BACKGROUND: Periodontal disease is highly prevalent amongst domestic cats, causing pain, gingival bleeding, reduced food intake, loss of teeth and possibly impacts on overall systemic health. Diet has been suggested to play a role in the development of periodontal disease in cats. There is a complete lack of information about how diet (composition and texture) affects the feline oral microbiome, the composition of which may influence oral health and the development of periodontal disease. We undertook a pilot study to assess if lifelong feeding of dry extruded kibble or wet (canned and/or fresh meat combinations) diets to cats (n = 10) with variable oral health affected the microbiome. RESULTS: Oral microbiome composition was assessed by amplifying the V1-V3 region of the 16S gene from supragingival dental plaque DNA extracts. These amplicons were sequenced using Illumina technology. This deep sequencing revealed the feline oral microbiome to be diverse, containing 411 bacterial species from 14 phyla. We found that diet had a significant influence on the overall diversity and abundance of specific bacteria in the oral environment. Cats fed a dry diet exclusively had higher bacterial diversity in their oral microbiome than wet-food diet cats (p < 0.001). Amongst this higher diversity, cats on dry-food diets had a higher abundance of Porphyromonas spp. (p < 0.01) and Treponema spp. (p < 0.01). CONCLUSIONS: While we observed differences in the oral microbiome between cats on the two diets assessed, the relationship between these differences and gingival health was unclear. Our preliminary results indicate that further analysis of the influence of dietary constituents and texture on the feline oral microbiome is required to reveal the relationship between diet, the oral microbiome and gingival health in cats. PMID- 27277500 TI - Role of serotonin in the regulation of renal proximal tubular epithelial cells. AB - In various renal injuries, tissue damage occurs and platelet activation is observed. Recent studies suggest that some factors, such as serotonin, are released into microenvironment upon platelet activation following renal injury. In the present study, we aimed to investigate whether platelets and platelet released serotonin are involved in the functional regulation of renal proximal tubular epithelial cells (PTECs). PTECs were obtained by primary cell culture and treated with platelet lysate (PL) (2 * 10(6)/mL, 4 * 10(6)/mL, 8 * 10(6)/mL) or serotonin (1 MUM or 5 MUM) for 12 or 24 h. Phenotypic transdifferentiation of epithelial cells into myofibroblasts were demonstrated under light microscope and confirmed by the determination of alpha-smooth muscle actin gene expression. Serotonin and PL were shown to induce epithelial-mesenchymal transdifferentiation of PTECs. After stimulation of PTECs with serotonin or PL, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and collagen-alpha1 gene expressions, which were reported to be elevated in renal injury, were determined by real-time PCR and found to be upregulated. Expressions of some inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta1 were found to be increased in both protein and gene levels. Recently there is no published report on the effect of serotonin on renal PTECs. Results obtained in this study have lightened the role of serotonin and platelet-mediated effects of serotonin on fibrotic and inflammatory processes in PTECs. PMID- 27277501 TI - Identification of G protein-coupled receptors required for vitellogenin uptake into the oocytes of the red flour beetle, Tribolium castaneum. AB - Previous studies suggested that a membrane receptor might be involved in mediating vitellogenin (Vg) uptake and juvenile hormone (JH)-regulated remodeling of follicular epithelium (also called 'patency'). G protein-coupled receptor (GPCR) family is one of the largest membrane receptor protein families and controls many key physiological processes. To investigate the role of GPCRs in insect reproduction and juvenile hormone-regulated Vg uptake, we performed a comprehensive RNA interference (RNAi) screen targeting GPCRs in the red flour beetle, Tribolium castaneum. Out of 112 GPCRs tested, knockdown of 41 GPCRs resulted in a reduction in fecundity. Interestingly, RNAi against two GPCRs (a Rhodopsin-like receptor and a Dopamine D2-like receptor) led to a significant reduction in Vg accumulation in developing oocytes. Functional assays of these two GPCRs showed that JH triggers a dose-dependent inhibition of intracellular cAMP levels in HEK293 cells expressing Tribolium Dopamine D2-like receptor. These data suggest that Dopamine D2-like receptor plays crucial roles in regulating Vg uptake and is a promising candidate membrane receptor mediating JH regulation of patency in the red flour beetle. PMID- 27277502 TI - Patient preparation for cardiac fluorine-18 fluorodeoxyglucose positron emission tomography imaging of inflammation. AB - Although the number of clinical applications for fluorine-18 fluorodeoxyglucose (18F-FDG) cardiac positron emission tomography (PET) has continued to grow, there remains a lack of consensus regarding the ideal method of suppressing normal myocardial glucose utilization for image optimization. This review describes various patient preparation protocols that have been used as well as the success rates achieved in different studies. Collectively, the available literature supports using a high-fat, no-carbohydrate diet for at least two meals with a fast of 4-12 hours prior to 18F-FDG PET imaging and suggests that isolated fasting for less than 12 hours and supplementation with food or drink just prior to imaging should be avoided. Each institution should adopt a protocol and continuously monitor its effectiveness with a goal to achieve adequate myocardial suppression in greater than 80% of patients. PMID- 27277517 TI - The impact of oral rehabilitation on oral health-related quality of life in patients receiving radiotherapy for the treatment of head and neck cancer. AB - OBJECTIVES: To analyze the influence of dental treatment on oral health-related quality of life (OHRQoL) in head and neck cancer patients. MATERIALS AND METHODS: This study included the data of 116 patients who underwent radiotherapy (RT) because of head and neck cancer. For each patient, the variables age, sex, tumor site, irradiation technique, dose on the spared parotid gland, concomitant chemotherapy, and denture status were documented. OHRQoL was determined using the OHIP-G14 questionnaire. Patients were divided into subgroups according to denture status: none or fixed partial dentures (none/FPD), removable partial dentures (RPD), and full dentures (CD). OHIP summary scores were determined and tested for clinical relevant differences with respect to the different variables. The association between OHRQol and the variables was assessed using linear regression. RESULTS: No clinically relevant influence on OHRQoL was found for gender, irradiation technique, and chemotherapy. Patients with tumors located in the oral cavity had a significantly higher OHIP score than patients with other tumor sites (p < 0.001). None/FPD and RPD patients had higher values than those found in a normal population, but did not differ significantly from each other (p = 0.387). CONCLUSIONS: In contrast to tumor site, teeth and type of denture seem to have a limited effect on OHRQoL in head and neck cancer patients. CLINICAL SIGNIFICANCE: Prosthetic treatment in head and neck cancer patients do not lead to the same improvement in OHRQoL as found in the normal population. This might be taken into account especially if extensive dental treatment is intended. PMID- 27277519 TI - An effort to assess the relation between productivity loss costs and presenteeism at work. AB - PURPOSE: This study assesses potential presenteeism costs and the association of these with a company's business figures. MATERIALS AND METHODS: We conducted the questionnaire surveys in alternate years between 2003 and 2007 and linked them to sickness absence register data. Perceived work ability levels were assessed and converted into presenteeism days using the Presenteeism Scale tool. Sickness absence and presenteeism days were converted into monetary figures using median monthly salary information. RESULTS: The share of presenteeism costs was constant at about 1% of annual turnover and about 3.7% of personnel costs. The lowest annual presenteeism cost per employee was EUR 986 and the highest was EUR 1302. The lowest number of presenteeism days per employee in a year was 8.7 days and the highest number was 10.4 days. Estimated losses to a company due to sickness absences and presenteeism ranged from EUR 4.6 million to EUR 5.6 million annually. The potential presenteeism costs to the company and to Finnish society were vast. CONCLUSIONS: Presenteeism is a costly problem but more research is needed to reveal the connections between presenteeism and a company's turnover, personnel costs and profit. PMID- 27277518 TI - Randomized trial investigating zirconia electroplated telescopic retainers: quality of life outcomes. AB - OBJECTIVES: The study aims to evaluate the effect of electroplated telescopic removable dental prostheses (E-RDPs) with zirconia primary crowns on oral-health related quality of life (OHRQoL). MATERIALS AND METHODS: For E-RDPs, electroplating is used to produce precisely fitting gold copings on telescopic primary crowns. These copings are bonded intra-orally to the denture framework. Fifty-six participants in need of 60 removable restorations were randomly allocated one of two materials for the primary crowns: cobalt-chromium alloy or zirconia. OHRQoL was assessed by use of the 49-item Oral Health Impact Profile (OHIP-49) and by additional patient self-rating at baseline before treatment, and after 6 and 12 months. Statistical analysis was performed by use of one- and two sample t-tests and analysis of covariance. RESULTS: Mean OHIP sum score at baseline was 53.4 (SD 37.4, 95 % CI 41.3-62). At follow-ups, it decreased significantly (after 6 months: mean 20, SD 26, 95 % CI 13-27.1; after 12 months: mean 16.4, SD 17.9, 95 % CI 11.6-21.2). The mean reduction in OHIP sum score after 12 months was 25 (SD 31.2, 95 % CI 13.1-36.9) for cobalt-chromium alloy and 44.4 (SD 32.3, 95 % CI 31.1-57.8) for zirconia. However, no statistically significant difference of the two materials on OHIP change or patient self-rating was detected. CONCLUSIONS: Although OHRQoL was improved by using both cobalt chromium alloy and zirconia primary crowns for E-RDPs, post-treatment differences between the groups were not statistically significant. CLINICAL RELEVANCE: Zirconia E-RDPs enhance OHRQoL. However, zirconia primary crowns do not outperform cobalt-chromium alloy crowns regarding patient satisfaction-despite their tooth-like color. PMID- 27277520 TI - Roles of the glutathione- and thioredoxin-dependent systems in the Escherichia coli responses to ciprofloxacin and ampicillin. AB - Recently, it was proposed that some antibiotics stimulate the production of reactive oxygen species (ROS), which contribute to cell death. Later, other research groups have provided arguments against ROS-mediated killing of bacteria by antibiotics. At present, there remain a number of unanswered questions in understanding of the role of ROS in killing by antibiotics. Mutants of Escherichia coli in components of the thioredoxin and glutaredoxin redox pathways used in this study possess a great variability in antioxidant activity, and they therefore are a useful model for the investigation of the role of oxidative stress in bactericidal effect of antibiotics. Statistical analysis did not reveal a significant correlation between the susceptibility of the mutants to ciprofloxacin and ampicillin and their resistance to peroxide stress. However, we found strong reverse correlations between the bactericidal activity of antibiotics and the specific growth rate of these mutants at the moment of drug addition. Supplements changing the level of intra- and extracellular glutathione considerably affected E. coli susceptibility to ciprofloxacin and ampicillin. The effect of GSH precursors on bactericidal activity of antibiotics was also observed in gshA mutants. PMID- 27277521 TI - Engineered disorder and light propagation in a planar photonic glass. AB - The interaction of light with matter strongly depends on the structure of the latter at wavelength scale. Ordered systems interact with light via collective modes, giving rise to diffraction. In contrast, completely disordered systems are dominated by Mie resonances of individual particles and random scattering. However, less clear is the transition regime in between these two extremes, where diffraction, Mie resonances and near-field interaction between individual scatterers interplay. Here, we probe this transitional regime by creating colloidal crystals with controlled disorder from two-dimensional self-assembly of bidisperse spheres. Choosing the particle size in a way that the small particles are transparent in the spectral region of interest enables us to probe in detail the effect of increasing positional disorder on the optical properties of the large spheres. With increasing disorder a transition from a collective optical response characterized by diffractive resonances to single particles scattering represented by Mie resonances occurs. In between these extremes, we identify an intermediate, hopping-like light transport regime mediated by resonant interactions between individual spheres. These results suggest that different levels of disorder, characterized not only by absence of long range order but also by differences in short-range correlation and interparticle distance, exist in colloidal glasses. PMID- 27277522 TI - Significantly enhanced proteolytic activity of cyclen complexes by monoalkylation. AB - A simple approach towards efficient artificial proteases based on the cyclen ligand is presented. We thus achieved an increase of the proteolytic activity of two orders of magnitude when compared to the unsubstituted cyclen complex. Amphiphilic Cu(ii) and Co(iii) complexes cut BSA and myoglobin as model substrates at MUM concentrations. MALDI-ToF MS is used to identify the cleavage fragments. PMID- 27277523 TI - Medical Registry Data Collection Efficiency: A Crossover Study Comparing Web Based Electronic Data Capture and a Standard Spreadsheet. AB - BACKGROUND: Electronic medical records and electronic data capture (EDC) have changed data collection in clinical and translational research. However, spreadsheet programs, such as Microsoft Excel, are still used as data repository to record and organize patient data for research. OBJECTIVE: The objective of this study is to assess the efficiency of EDC as against a standard spreadsheet in regards to time to collect data and data accuracy, measured in number of errors after adjudication. METHODS: This was a crossover study comparing the time to collect data in minutes between EDC and a spreadsheet. The EDC tool used was Research Electronic Data Capture (REDCap), whereas the spreadsheet was Microsoft Excel. The data collected was part of a registry of patients who underwent coronary computed tomography angiography in the emergency setting. Two data collectors with the same experience went over the same patients and collected relevant data on a case report form identical to the one used in our Emergency Department (ED) registry. Data collection tool was switched after the patient that represented half the cohort. For this, the patient cohort was exactly 30 days of our ED coronary Computed Tomography Angiography registry and the point of crossover was determined beforehand to be 15 days. We measured the number of patients admitted, and time to collect data. Accuracy was defined as absence of blank fields and errors, and was assessed by comparing data between data collectors and counting every time the data differed. Statistical analysis was made using paired t -test. RESULTS: The study included 61 patients (122 observations) and 55 variables. The crossover occurred after the 30th patient. Mean time to collect data using EDC in minutes was 6.2+/-2.3, whereas using Excel was 8.0+/-2.0 (P <.001), a difference of 1.8 minutes between both means (22%). The cohort was evenly distributed with 3 admissions in the first half of the crossover and 4 in the second half. We saw 2 (<0.1%) continuous variable typos in the spreadsheet that a single data collector made. There were no blank fields. The data collection tools showed no differences in accuracy of data on comparison. CONCLUSIONS: Data collection for our registry with an EDC tool was faster than using a spreadsheet, which in turn allowed more efficient follow-up of cases. PMID- 27277525 TI - Lubricant sensitivity in function of paddle movement in the forced feeder of a high-speed tablet press. AB - CONTEXT: The negative impact of magnesium stearate (MgSt) on the hardness of tablets is a well-known phenomenon, but the influence of paddle movement in the forced feeder on the lubricant effect during tablet compression is often neglected. OBJECTIVE: The purpose of this research was to investigate the influence of paddle speed in the forced feeder on tablet tensile strength (TS). MATERIALS AND METHODS: Mixtures of microcrystalline cellulose (MCC) and MgSt (0.5%) were blended using different methods (low & high shear). After blending, the formulations were compressed into tablets. All parameters of the tableting cycle were kept constant except the speed of the paddles in the forced feeder. RESULTS AND DISCUSSION: The blending technique affected the sensitivity of the formulation to the paddle speed. The TS of pure MCC tablets did not change in function of paddle speed, while tablets prepared by low shear mixing became softer at higher paddle speed. The TS of tablets manufactured using the high shear mixed blend was low and did not vary in function of paddle speed, suggesting that overlubrication already occurred during the initial blending step. Furthermore, analysis of the machine parameters allowed evaluation of the influence of the paddles on the flowability, initial packing, and compactability of the powder mixtures. CONCLUSION: The results elucidated that during manufacturing of tablets using MgSt-containing blends care should not only be taken during the blending step prior to tableting, but also during the tableting process itself, as paddle speed can affect tablet TS, a critical quality attribute. PMID- 27277526 TI - Adulthood revictimization: looking beyond childhood trauma. PMID- 27277524 TI - Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment. AB - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in inhabitants from low-income countries and in visitors to these countries. The impact of the human intestinal microbiota on the initiation and progression of ETEC diarrhea is not yet well understood. RESULTS: We used 16S rRNA (ribosomal RNA) gene sequencing to study changes in the fecal microbiota of 12 volunteers during a human challenge study with ETEC (H10407) and subsequent treatment with ciprofloxacin. Five subjects developed severe diarrhea and seven experienced few or no symptoms. Diarrheal symptoms were associated with high concentrations of fecal E. coli as measured by quantitative culture, quantitative PCR, and normalized number of 16S rRNA gene sequences. Large changes in other members of the microbiota varied greatly from individual to individual, whether or not diarrhea occurred. Nonetheless the variation within an individual was small compared to variation between individuals. Ciprofloxacin treatment reorganized microbiota populations; however, the original structure was largely restored at one and three month follow-up visits. CONCLUSION: Symptomatic ETEC infections, but not asymptomatic infections, were associated with high fecal concentrations of E. coli. Both infection and ciprofloxacin treatment caused variable changes in other bacteria that generally reverted to baseline levels after three months. PMID- 27277527 TI - The role of quantitation of real-time 3-dimensional contrast-enhanced ultrasound in detecting microvascular invasion: an in vivo study. AB - PURPOSE: This study was to evaluate the role of quantitative perfusion analysis of 3-dimensional (3D) contrast-enhanced ultrasound (CEUS) in detecting microvascular invasion (MVI) of liver tumor in vivo. METHODS: VX2 tumors were implanted in the livers of sixteen New Zealand rabbits. On day 10, real-time 3D CEUS was performed, and the real-time dynamic images were analyzed using online quantification software. The animals were sacrificed and sent for pathology examinations. According to the gold standard of pathology, the animals were divided into an MVI group and a group without MVI (non-MVI group). Time-intensity curves (TICs) were obtained for the VX2 tumors and the surrounding liver parenchyma, and the parameters peak intensity (PI), mean transit time (MTT), and time to peak (TTP) were compared within and between the MVI and non-MVI groups. RESULTS: The TTP and MTT of the VX2 tumors were significantly faster than those of the surrounding liver parenchyma in both MVI and non-MVI groups. The PI of the VX2 tumors was significantly lower than that of the surrounding liver parenchyma in the non-MVI group but not the MVI group. The TTP and MTT of the VX2 tumors and surrounding liver parenchyma were not significantly different in the MVI group compared with the non-MVI group, whereas the DeltaPI (the PI ratio between the VX2 liver tumors and the reference liver parenchyma) of the VX2 tumors in the MVI group was larger than that in the non-MVI group. VX2 tumors with MVI present different hemodynamic parameters, with a larger DeltaPI than tumors without MVI. CONCLUSIONS: Our data suggest that quantitative perfusion analysis of 3D CEUS might be a promising method for predicting MVI in liver tumors. PMID- 27277528 TI - Cancer therapy-related complications in the bowel and mesentery: an imaging perspective. AB - Cancer therapy-induced complications in the bowel and mesentery are fairly common. It is important for clinicians to be aware of these complications and the agents most frequently implicated. Cancer therapy is rapidly evolving and often encompasses both classic cytotoxic drugs and newer molecular targeted agents. Drugs from both broad classes can have numerous adverse effects on the bowel and mesentery that can be detected on imaging. These adverse effects include ileus, various forms of enterocolitis, gastrointestinal perforation, pneumatosis intestinalis, secretory diarrhea, and sclerosing mesenteritis. These complications are diverse and range from relatively benign to life threatening. The management is also variable, but many of these conditions are easily controlled and reversed with supportive care and cessation of the particular cancer therapy. The objective of this pictorial essay is to demonstrate some of the more common cancer therapy-induced complications of the bowel and mesentery, with a focus on the radiographic findings. PMID- 27277529 TI - Slug inhibition increases radiosensitivity of oral squamous cell carcinoma cells by upregulating PUMA. AB - As a new strategy, radio-gene therapy was widely used for the treatment of cancer patients in recent few years. Slug was involved in the radioresistance of various cancers and has been found to have an anti-apoptotic effect. This study aims to investigate whether the modulation of Slug expression by siRNA affects oral squamous cell carcinoma sensitivity to X-ray irradiation through upregulating PUMA. Two oral squamous cell carcinoma cell lines (HSC3 and HSC6) were transfected with small interfering RNA (siRNA) targeting Slug and subjected to radiotherapy in vitro. After transfection with Slug siRNA, both HSC3 and HSC6 cells showed relatively lower expression of Slug and higher expression of PUMA. The Slug siRNA transfected cells showed decreased survival and proliferation rates, an increased apoptosis rate and enhanced radiosensitivity to X-ray irradiation. Our results revealed that Slug siRNA transfection in combination with radiation increased the expression of PUMA, which contributed to radiosensitivity of oral squamous cell carcinoma cells. Thus, controlling the expression of Slug might contribute to enhance sensitivity of HSC3 and HSC6 cells toward X-ray irradiation in vitro by upregulating PUMA. PMID- 27277531 TI - Acute-on-chronic liver failure in cirrhosis. PMID- 27277530 TI - Hydroxychloroquine protects melanocytes from autoantibody-induced injury by reducing the binding of antigen-antibody complexes. AB - Vitiligo is a polygenic autoimmune disorder characterized by loss of pigmentation due to melanocyte destruction. Hydroxychloroquine (HCQ) is an effective immunosuppressant widely used in the treatment of autoimmune disorders. As generalized vitiligo (GV) is commonly considered to be a T cell and autoantibody induced immune disorder, the present study aimed to determine whether HCQ protects melanocytes from autoantibody-induced disruption. Anti-melanocyte antibodies were obtained from the serum of patients with progressive GV and the effects of HCQ on prevent the autoantibody-induced disruption of melanocytes was observed. Cell-based ELISA, indirect immunofluorescence and western blotting were used to analyze the autoantibody content of sera samples obtained from 32 patients with progressive GV. The cytotoxicity of HCQ was detected by MTT assay, and 1 ug/ml HCQ was applied to human primary melanocytes (HMCs) to examine whether it could exert protective effects against autoantibody-induced immune injury. Flow cytometry was used to measure autoantibody binding to the surface of HMCs. Complement-dependent cytotoxicity (CDC) and antibody-dependent cell mediated cytotoxicity (ADCC) were monitored by MTT and lactate dehydrogenase releasing assays. The concentration of autoantibodies in sera samples taken from GV patients was significantly higher than in controls, particularly in patients who had >10% of their body surface affected by vitiligo. The majority of the autoantibodies presented in the HMCs and human keratinocytes (HKCs) and were predominantly localized to the cell surface and cytoplasm. The molecular weights of the autoantigens were identified as 30, 37-39, 42, 53, 60-75, 90, 100, 110, and 126 kDa; the 30 kDa protein was observed only in HMCs. The addition of HCQ at a concentration of 1 ug/ml produced no significant cytotoxicity in HMCs and was demonstrated to reduce the binding of GV immunoglobulin G (IgG) to the surface of HMCs. HCQ also significantly decreased the effects of ADCC and CDC that were mediated by GV IgG. The present study provides evidence that HCQ dissociates autoantibody-antigen complexes on the surface of HMCs and reverses ADCC and CDC activity in vitro. Thus, in addition to its effectiveness as an antimalarial therapeutic agent, HCQ may also be a promising potential treatment for patients with vitiligo. PMID- 27277532 TI - Characterization of the recombinant Brettanomyces anomalus beta-glucosidase and its potential for bioflavouring. AB - AIM: Plant materials used in the food industry contain up to five times more aromas bound to glucose (glucosides) than free, unbound aromas, making these bound aromas an unused flavouring potential. The aim of this study was to identify and purify a novel beta-glucosidase from Brettanomyces yeasts that are capable of releasing bound aromas present in various food products. METHODS AND RESULTS: We screened 428 different yeast strains for beta-glucosidase activity and are the first to sequence the whole genome of two Brettanomyces yeasts (Brettanomyces anomalus and Brettanomyces bruxellensis) with exceptionally high beta-glucosidase activity. Heterologous expression and purification of the identified B. anomalus beta-glucosidase showed that it has an optimal activity at a higher pH (5.75) and lower temperature (37 degrees C) than commercial beta glucosidases. Adding this B. anomalus beta-glucosidase to cherry beers and forest fruit milks resulted in increased amounts of benzyl alcohol, eugenol, linalool and methyl salicylate compared to Aspergillus niger and Almond glucosidase. CONCLUSIONS: The newly identified B. anomalus beta-glucosidase offers new possibilities for food bioflavouring. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to sequence the B. anomalus genome and to identify the beta glucosidase-encoding genes of two Brettanomyces species, and reports a new bioflavouring enzyme. PMID- 27277534 TI - MicroRNA-320 was downregulated in non-small cell lung cancer and inhibited cell proliferation, migration and invasion by targeting fatty acid synthase. AB - The expression and functions of microRNA (miR)-320 have been previously investigated in various types of cancer. However, to the best of our knowledge, no previous studies have investigated miR-320 in human lung cancer. The current study determined the expression, biological functions and molecular mechanisms of miR-320 in human lung cancer. The expression level of miR-320 in human non-small cell lung cancer (NSCLC) and normal adjacent tissue samples (NATs), NSCLC cell lines and non-tumorigenic bronchial epithelial cells was measured by reverse transcription-quantitative polymerase chain reaction. Following transfection with miR-320 mimics, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell migration and cell invasion assays, western blot analysis and luciferase assay were performed in human NSCLC cell lines. The results demonstrated that miR 320 was significantly downregulated in NSCLC tissue samples and cell lines compared with NATs and a control cell line, respectively. Statistical analysis demonstrated that expression of miR-320 was significantly associated with the TNM classification and metastasis. It was also observed that miR-320 inhibited cell growth, migration and invasion in NSCLC cells. Additionally, the present study provided evidence that miR-320 may directly target fatty acid synthase. These results suggest that miR-320 may serve as a therapeutic biomarker of NSCLC in the future. PMID- 27277533 TI - Analysis of the genetic diversity and structure across a wide range of germplasm reveals prominent gene flow in apple at the European level. AB - BACKGROUND: The amount and structure of genetic diversity in dessert apple germplasm conserved at a European level is mostly unknown, since all diversity studies conducted in Europe until now have been performed on regional or national collections. Here, we applied a common set of 16 SSR markers to genotype more than 2,400 accessions across 14 collections representing three broad European geographic regions (North + East, West and South) with the aim to analyze the extent, distribution and structure of variation in the apple genetic resources in Europe. RESULTS: A Bayesian model-based clustering approach showed that diversity was organized in three groups, although these were only moderately differentiated (FST = 0.031). A nested Bayesian clustering approach allowed identification of subgroups which revealed internal patterns of substructure within the groups, allowing a finer delineation of the variation into eight subgroups (FST = 0.044). The first level of stratification revealed an asymmetric division of the germplasm among the three groups, and a clear association was found with the geographical regions of origin of the cultivars. The substructure revealed clear partitioning of genetic groups among countries, but also interesting associations between subgroups and breeding purposes of recent cultivars or particular usage such as cider production. Additional parentage analyses allowed us to identify both putative parents of more than 40 old and/or local cultivars giving interesting insights in the pedigree of some emblematic cultivars. CONCLUSIONS: The variation found at group and subgroup levels may reflect a combination of historical processes of migration/selection and adaptive factors to diverse agricultural environments that, together with genetic drift, have resulted in extensive genetic variation but limited population structure. The European dessert apple germplasm represents an important source of genetic diversity with a strong historical and patrimonial value. The present work thus constitutes a decisive step in the field of conservation genetics. Moreover, the obtained data can be used for defining a European apple core collection useful for further identification of genomic regions associated with commercially important horticultural traits in apple through genome-wide association studies. PMID- 27277536 TI - Novel "baby-in-mother" technique with the GuideLiner in the bifurcation coronary intervention with the protect-wire kept in the side branch. AB - We report a case of percutaneous coronary intervention in a bifurcation lesion involving the left anterior descending artery and the first-diagonal branch. The lesion was calcified with vessel tortuosity. Despite adequate lesion preparation using scoring balloon, the stent was not deliverable, even with deep intubation of 7Fr-guiding catheter. The use of 6-in-7 guiding extension catheter would have required removal of wire from the diagonal branch. To avoid this situation, we down-sized the extension catheter to 5Fr, which was successful in delivering the stent without removal of the wire from diagonal branch. We have also demonstrated this novel technique on ex vivo bench testing. PMID- 27277535 TI - A novel CCM2 variant in a family with non-progressive cognitive complaints and cerebral microbleeds. AB - Lobar cerebral microbleeds are most often sporadic and associated with Alzheimer's disease. The aim of our study was to identify the underlying genetic defect in a family with cognitive complaints and multiple lobar microbleeds and a positive family history for early onset Alzheimer's disease. We performed exome sequencing followed by Sanger sequencing for validation purposes on genomic DNA of three siblings with cognitive complaints, reduced amyloid-beta-42 in CSF and multiple cerebral lobar microbleeds. We checked for the occurrence of the variant in a cohort of 363 patients with early onset dementia and/or microbleeds. A novel frameshift variant (c.236_237delAC) generating a premature stop codon in the CCM2 gene shared by all three siblings was identified. Pathogenicity of the variant was supported by the presence of cerebral cavernous malformations in two of the siblings and by the absence of the variant exome variant databases. Two siblings were homozygous for APOE-epsilon4; one heterozygous. The cognitive complaints, reduced amyloid-beta-42 in CSF and microbleeds suggest preclinical Alzheimer's disease, but the stability of the cognitive complaints does not. We hypothesize that the phenotype in this family may be due to a combination of the CCM2 variant and the APOE status. (c) 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID- 27277537 TI - Drinking water insecurity: water quality and access in coastal south-western Bangladesh. AB - National drinking water assessments for Bangladesh do not reflect local variability, or temporal differences. This paper reports on the findings of an interdisciplinary investigation of drinking water insecurity in a rural coastal south-western Bangladesh. Drinking water quality is assessed by comparison of locally measured concentrations to national levels and water quality criteria; resident's access to potable water and their perceptions are based on local social surveys. Residents in the study area use groundwater far less than the national average; salinity and local rainwater scarcity necessitates the use of multiple water sources throughout the year. Groundwater concentrations of arsenic and specific conductivity (SpC) were greater than surface water (pond) concentrations; there was no statistically significant seasonal difference in mean concentrations in groundwater, but there was for ponds, with arsenic higher in the dry season. Average arsenic concentrations in local water drinking were 2 4 times times the national average. All of the local groundwater samples exceeded the Bangladesh guidance for SpC, although the majority of residents surveyed did not perceive their water as having a 'bad' or 'salty' taste. PMID- 27277538 TI - Selective inhibition of apicoplast tryptophanyl-tRNA synthetase causes delayed death in Plasmodium falciparum. AB - The malaria parasite Plasmodium falciparum relies on efficient protein translation. An essential component of translation is the tryptophanyl-tRNA synthetase (TrpRS) that charges tRNA(trp). Here we characterise two isoforms of TrpRS in Plasmodium; one eukaryotic type localises to the cytosol and a bacterial type localises to the remnant plastid (apicoplast). We show that the apicoplast TrpRS aminoacylates bacterial tRNA(trp) while the cytosolic TrpRS charges eukaryotic tRNA(trp). An inhibitor of bacterial TrpRSs, indolmycin, specifically inhibits aminoacylation by the apicoplast TrpRS in vitro, and inhibits ex vivo Plasmodium parasite growth, killing parasites with a delayed death effect characteristic of apicoplast inhibitors. Indolmycin treatment ablates apicoplast inheritance and is rescuable by addition of the apicoplast metabolite isopentenyl pyrophosphate (IPP). These data establish that inhibition of an apicoplast housekeeping enzyme leads to loss of the apicoplast and this is sufficient for delayed death. Apicoplast TrpRS is essential for protein translation and is a promising, specific antimalarial target. PMID- 27277540 TI - Bulk binary ZrO2-based oxides as highly active alternative-type catalysts for non oxidative isobutane dehydrogenation. AB - Bulk binary ZrO2-based oxides efficiently catalyse non-oxidative dehydrogenation of isobutane to isobutylene. Their activity strongly depends on the kind of second metal oxide. So designed CrZrOx showed superior activity to industrially relevant catalysts with supported Pt or CrOx species. It was also stable under alternating dehydrogenation and oxidative regeneration cycles over ca. 110 h under different reaction conditions between 550 and 600 degrees C. PMID- 27277539 TI - Identification of a new HLA-G allele, HLA-G*01:19, by cloning and phasing. AB - A new HLA-G allelic variant, HLA-G*01:19, was identified in a southern Chinese Han population by polymerase chain reaction-sequence-based typing (PCR-SBT), cloning and phasing. HLA-G*01:19 differs from HLA-G*01:04:01 by a nonsynonymous cytosine at position 99 in exon 2, resulting in amino acid change from valine to leucine at codon 34 of the mature HLA-G molecule. PMID- 27277541 TI - Proteasome inhibitor MG132 potentiates TRAIL-induced apoptosis in gallbladder carcinoma GBC-SD cells via DR5-dependent pathway. AB - TRAIL is a tumor-selective apoptosis-inducing cytokine playing a vital role in the surveillance and elimination of some tumor cells. However, some tumors are resistant to TRAIL treatment. Proteasome inhibitor MG132 exhibits anti proliferative and pro-apoptotic properties in many tumors. In this study, we demonstrated that proteasome inhibitor MG132 in vitro and in vivo potentiates TRAIL-induced apoptosis in gallbladder carcinoma GBC-SD cells. MG132 was able to inhibit the proliferation of GBC-SD cells and induce apoptosis in a dose dependent manner. The induction of apoptosis by proteasome inhibitor MG132 was mainly through the extrinsic apoptotic pathways of caspase activation such as caspase-8, caspase-3 and PARP cleavage. In addition, this process was also dependent on the upregulation of death receptor 5 (DR5), which promoted TRAIL induced apoptosis in GBC-SD cells. Taken together, these findings indicate that MG132 possesses anti-gallbladder cancer potential that correlate with regulation of DR5-dependent pathway, and suggest that MG132 may be a promising agent for sensitizing GBC-SD cells to TRAIL-induced apoptosis. PMID- 27277542 TI - Vending Machines of Food and Beverages and Nutritional Profile of their Products at Schools in Madrid, Spain, 2014-2015. AB - BACKGROUND: Policies restricting access to sugary drinks and unhealthy foods in the school environment are associated with healthier consumption patterns. In 2010, Spain approved a Consensus Document regarding Food at Schools with nutritional criteria to improve the nutritional profile of foods and drinks served at schools. The objective of this study was to describe the frequency of food and drink vending machines at secondary schools in Madrid, the products offered at them and their nutritional profile. METHODS: Cross-sectional study of a random sample of 330 secondary schools in Madrid in 2014-2015. The characteristics of the schools and the existence of vending machines were recorded through the internet and by telephone interview. The products offered in a representative sample of 6 vending machines were identified by in situ inspection, and its nutritional composition was taken from its labeling. Finally, the nutritional profile of each product was analyzed with the United Kingdom profile model, which classifies products as healthy and less healthy. RESULTS: The prevalence of vending machines was 17.3%. Among the products offered, 80.5% were less healthy food and drinks (high in energy, fat or sugar and poor in nutrients) and 10.5% were healthy products. CONCLUSIONS: Vending machines are common at secondary schools in Madrid. Most products are vending machines are still less healthy. PMID- 27277543 TI - Ultrasound characterization of the mastoid for detecting middle ear effusion: A preliminary clinical validation. AB - Ultrasound detection of middle ear effusion (MEE) is an emerging technique in otolaryngology. This study proposed using ultrasound characterization of the mastoid to noninvasively measure MEE-induced mastoid effusion (ME) as a new strategy for determining the presence of MEE. In total, 53 patients were enrolled (Group I: normal, n = 20; Group II: proven MEE through both otoscopy and tympanometry, n = 15; Group III: patients with MEE having effusions observed during grommet surgery, n = 18). A 2.25-MHz delay-line transducer was used to measure backscattered signals from the mastoid. The Nakagami parameter was estimated using the acquired signals to model the echo amplitude distribution for quantifying changes in the acoustic structures of mastoid air cells. The median Nakagami parameter and interquartile range were 0.35 (0.34-0.37) for Group I, 0.39 (0.37-0.41) for Group II, and 0.43 (0.39-0.51) for Group III. The echo amplitude distribution observed for patients with MEE was closer to Rayleigh distribution than that without MEE. Receiver operating characteristic (ROC) curve analysis further revealed that the area under the ROC was 0.88, sensitivity was 72.73%, specificity was 95%, and accuracy was 81.13%. The proposed method has considerable potential for noninvasive and comfortable evaluation of MEE. PMID- 27277544 TI - A facile one-step folic acid modified partially oxidized graphene for high sensitivity tumor cell sensing. AB - A highly sensitive and selective tumor cell sensor based on partially oxidized graphene (POG) and folate acid (FA) composite was constructed. The POG was prepared through a modified Hummers method and characterized by means of Raman spectroscopy, X-ray photoelectron spectroscopy, cyclic voltammetry, atomic force microscopy and transmission electron microscopy. The as-prepared POG exhibited the advantages of high electrochemical activity and a good capacity of linking amine derivatives. Using a facile one step reaction, the FA-modified POG was endowed with a more sensitive response to folate-expressing tumor cells than those sensors constructed by the two-step reaction, as well as high selectivity, good reproducibility and long-term stability. PMID- 27277545 TI - Letter to 'Cervical varix complicated by placenta previa: A case report and literature review': A novel simple abdominal traction stitch (Matsubara) to hold the Bakri balloon. PMID- 27277546 TI - Ordered genome change of plant and animal body cells revealed by the genome profiling method. AB - In the past, it was widely thought that, although epigenetically different, the genome sequences of cells are basically the same in a single body. In retrospect, the genome-uniformity idea may have been naive, considering that DNA polymerases cannot be perfect. Here, a systemic, not sporadic, genome change was demonstrated in a single plant (Arabidopsis) and animal (zebrafish) body using genome DNAs taken in an ordered manner using the genome profiling method. This can be explained because mutations accumulate additively in progeny cells, and these results are critically significant for developmental and oncological research. PMID- 27277547 TI - Arctic cut-off high drives the poleward shift of a new Greenland melting record. AB - Large-scale atmospheric circulation controls the mass and energy balance of the Greenland ice sheet through its impact on radiative budget, runoff and accumulation. Here, using reanalysis data and the outputs of a regional climate model, we show that the persistence of an exceptional atmospheric ridge, centred over the Arctic Ocean, was responsible for a poleward shift of runoff, albedo and surface temperature records over the Greenland during the summer of 2015. New records of monthly mean zonal winds at 500 hPa and of the maximum latitude of ridge peaks of the 5,700+/-50 m isohypse over the Arctic were associated with the formation and persistency of a cutoff high. The unprecedented (1948-2015) and sustained atmospheric conditions promoted enhanced runoff, increased the surface temperatures and decreased the albedo in northern Greenland, while inhibiting melting in the south, where new melting records were set over the past decade. PMID- 27277548 TI - Italian Chapter of the International Society of Cardiovascular Ultrasound expert consensus document on coronary computed tomography angiography: overview and new insights. AB - Coronary computed tomography angiography is a noninvasive heart imaging test currently undergoing rapid development and advancement. The high resolution of the three-dimensional pictures of the moving heart and great vessels is performed during a coronary computed tomography to identify coronary artery disease and classify patient risk for atherosclerotic cardiovascular disease. The technique provides useful information about the coronary tree and atherosclerotic plaques beyond simple luminal narrowing and plaque type defined by calcium content. This application will improve image-guided prevention, medical therapy, and coronary interventions. The ability to interpret coronary computed tomography images is of utmost importance as we develop personalized medical care to enable therapeutic interventions stratified on the bases of plaque characteristics. This overview provides available data and expert's recommendations in the utilization of coronary computed tomography findings. We focus on the use of coronary computed tomography to detect coronary artery disease and stratify patients at risk, illustrating the implications of this test on patient management. We describe its diagnostic power in identifying patients at higher risk to develop acute coronary syndrome and its prognostic significance. Finally, we highlight the features of the vulnerable plaques imaged by coronary computed tomography angiography. PMID- 27277549 TI - Isolation and characterization of tumorspheres from a recurrent pineoblastoma patient: Feasibility of a patient-derived xenograft. AB - The existence of tumorspheres (TSs) might confer treatment resistance to pineoblastoma (PB). The existence of PB TSs with cellular immortalization potential has not yet been reported. We developed a procedure for isolating TSs from recurrent PB (rPB) and tested whether their properties made them suitable for use as a patient-derived xenograft (PDX). Immunocytochemical staining, RT-PCR and quantitative real-time PCR showed that, among stemness proteins, CD133, musashi and podoplanin were expressed at elevated levels in rPB TSs, but nestin was not. rPB TSs cultured under neuro-glial differentiation conditions expressed TUBB3, but not GFAP, MBP or NeuN. Unlike glioblastoma TSs, rPB TSs showed no clear evidence of invasion in 3D invasion assay or increased expression of genes associated with epithelial-mesenchymal transition. An orthotopic xenograft showed that tumor xenografts replicated the histopathological features of the patient tumor and expressed similar genome profiles, as determined by short tandem repeat genotyping. These data demonstrate the isolation and the characterization of rPB TSs for the first time. Using an orthotopic xenograft, we showed that rPB TSs could replicate the patient tumor, demonstrating their potential as a PDX for precision medicine. PMID- 27277550 TI - Nuclear import of prototype foamy virus transactivator Bel1 is mediated by KPNA1, KPNA6 and KPNA7. AB - Bel1, a transactivator of the prototype foamy virus (PFV), plays pivotal roles in the replication of PFV. Previous studies have demonstrated that Bel1 bears a nuclear localization signal (NLS); however, its amino acid sequence remains unclear and the corresponding adaptor importins have not yet been identified. In this study, we inserted various fragments of Bel1 into an EGFP-GST fusion protein and investigated their subcellular localization by fluorescence microscopy. We found that the 215PRQKRPR221 fragment, which accords with the consensus sequence K(K/R)X(K/R) of the monopartite NLS, directed the nuclear translocation of Bel1. Point mutation experiments revealed that K218, R219 and R221 were essential for the nuclear localization of Bel1. The results of GST pull-down assay revealed that the Bel1 peptide 215-221, which bears the NLS, interacted with the nucleocytoplasmic transport receptors, karyopherin alpha 1 (importin alpha 5) (KPNA1), karyopherin alpha 6 (importin alpha 7) (KPNA6) and karyopherin alpha 7 (importin alpha 8) (KPNA7). Finally, in vitro nuclear import assays demonstrated that KPNA1, KPNA6 or KPNA7, along with other necessary nuclear factors, caused Bel1 to localize to the nucleus. Thus, the findings of our study indicate that KPNA1, KPNA6 and KPNA7 are involved in Bel1 nuclear distribution. PMID- 27277551 TI - Timing of Gestures: Gestures Anticipating or Simultaneous With Speech as Indexes of Text Comprehension in Children and Adults. AB - The deep comprehension of a text is tantamount to the construction of an articulated mental model of that text. The number of correct recollections is an index of a learner's mental model of a text. We assume that another index of comprehension is the timing of the gestures produced during text recall; gestures are simultaneous with speech when the learner has built an articulated mental model of the text, whereas they anticipate the speech when the learner has built a less articulated mental model. The results of four experiments confirm the predictions deriving from our assumptions for both children and adults. Provided that the recollections are correct, the timing of gestures can differ and can be considered a further measure of the quality of the mental model, beyond the number of correct recollections. PMID- 27277552 TI - A review on the important aspects of lipase immobilization on nanomaterials. AB - Lipase is one of the most widely used enzymes and plays an important role in biotechnological and industrial processes including food, paper, and oleochemical industries, as well as in pharmaceutical applications. However, its aqueous solubility and instability make its application relatively difficult and expensive. The immobilization technique is often used to improve lipase performance, and the strategy has turned out to be a promising method. Immobilized lipase on nanomaterials (NMs) has shown superiority to the free lipase, such as improved thermal and pH stability, longer stable time, and the capacity of being reused. However, immobilization of lipase on NMs also sometimes causes activity loss and protein loading is relatively lowered under some conditions. The overall performance of immobilized lipase on NMs is influenced by mechanisms of immobilization, type of NMs being used, and physicochemical features of the used NMs (such as particle size, aggregation behavior, NM dimension, and type of coupling/modifying agents being used). Based on the specific features of lipase and NMs, this review discusses the recent developments, some mechanisms, and influence of NMs on lipase immobilization and their activity. Multiple application potential of the immobilized lipases has also been considered. PMID- 27277553 TI - Cardiovascular regulation pattern of contamination-related disgust: Consistency and context dependence. AB - The cardiovascular response to contamination-related disgust was proposed to be under parasympathetic or parasympathetic-sympathetic cardiac control. However, findings of physiological disgust responses are inconsistent, possibly due to effects of the emotion induction context and single cardiovascular changes being part of larger cardiovascular regulation patterns. Therefore, we induced an emotionally neutral state and core and contamination disgust in female participants in two induction contexts (auditory script, film clip). Dependent variables were emotion self-reports and 10 cardiovascular factors derived from 23 cardiovascular variables. We found elevated disgust ratings in both induction contexts. On the cardiovascular level, we observed consistent increases in a factor indicating vagal cardiac control in both contexts and changes in factors indicating sympathetic activation that were bound to the respective context. These findings support the notion of a parasympathetic dominance of the contamination-related disgust response and underpin the importance of incorporating the induction context in the study of cardiovascular responses to disgust. PMID- 27277554 TI - Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans. AB - Human antimicrobial RNases, which belong to the vertebrate RNase A superfamily and are secreted upon infection, display a wide spectrum of antipathogen activities. In this work, we examined the antifungal activity of the eosinophil RNase 3 and the skin-derived RNase 7, two proteins expressed by innate cell types that are directly involved in the host defense against fungal infection. Candida albicans has been selected as a suitable working model for testing RNase activities toward a eukaryotic pathogen. We explored the distinct levels of action of both RNases on yeast by combining cell viability and membrane model assays together with protein labeling and confocal microscopy. Site-directed mutagenesis was applied to ablate either the protein active site or the key anchoring region for cell binding. This is the first integrated study that highlights the RNases' dual mechanism of action. Along with an overall membrane destabilization process, the RNases could internalize and target cellular RNA. The data support the contribution of the enzymatic activity for the antipathogen action of both antimicrobial proteins, which can be envisaged as suitable templates for the development of novel antifungal drugs. We suggest that both human RNases work as multitasking antimicrobial proteins that provide a first line immune barrier. PMID- 27277555 TI - Impact of targeted counseling on reported vaginal hygiene practices and bacterial vaginosis: the HIV Prevention Trials Network 035 study. AB - The objective of this study was to describe the impact of intense counseling to reduce vaginal hygiene practices and its effect on bacterial vaginosis. A secondary data analysis of the HIV Prevention Trials Network 035 study was undertaken, focusing on HIV-negative, nonpregnant women who were at least 18 years old, in seven African sites and one US site. At enrollment and during follow-up quarterly visits, vaginal hygiene practices were determined by face-to face administration of a behavioral assessment questionnaire. Vaginal hygiene practices were categorized as insertion into the vagina of (1) nothing, (2) water only, and (3) other substances with or without water. Each practice was quantified by frequency and type/combination of inserted substances. At quarterly visits, diagnosis of bacterial vaginosis was made using the Nugent score. Trends for vaginal hygiene practices and bacterial vaginosis were evaluated using generalized estimating equation models. A total of 3087 participants from the HIV Prevention Trials Network 035 study were eligible for this analysis. At enrollment, 1859 (60%) reported recent vaginal hygiene practices. By one year, this figure had decreased to 1019 (33%) with counseling. However, bacterial vaginosis prevalence remained consistent across the study observation period, with 36%-38% of women testing positive for the condition ( p for trend = 0.27). Overall, those who reported douching with water only (AOR = 1.03, 95%CI: 0.94 1.13) and those who reported inserting other substances (AOR= 0.98, 95%CI: 0.88 1.09) in the past quarter were not more likely to have bacterial vaginosis compared to those who reported no insertions. However, in South Africa, an increase in bacterial vaginosis was seen among those who reported inserting other substances (AOR: 1.48, 95%CI: 1.17, 1.88). In conclusion, targeted counseling against vaginal hygiene practices resulted in change in self-reported behavior but did not have an impact on bacterial vaginosis diagnosis in all but one site. PMID- 27277556 TI - [Laparoscopic rectal resection technique]. AB - The quality of radical oncological operations for patients with rectal cancer determines the rate of local recurrence and long-term survival. Neoadjuvant chemoradiotherapy for locally advanced tumors, a standardized surgical procedure for rectal tumors less than 12 cm from the anus with total mesorectal excision (TME) and preservation of the autonomous nerve system for sexual and bladder function have significantly improved the oncological results and quality of life of patients. The TME procedure for rectal resection has been performed laparoscopically in Germany for almost 20 years; however, no reliable data are available on the frequency of laparoscopic procedures in rectal cancer patients in Germany. The rate of minimally invasive procedures is estimated to be less than 20 %. A prerequisite for using the laparoscopic approach is implicit adherence to the described standards of open surgery. Available data from prospective randomized trials, systematic reviews and meta-analyses indicate that in the early postoperative phase the generally well-known positive effects of the minimally invasive approach to the benefit of patients can be realized without any long-term negative impact on the oncological results; however, the results of many of these studies are difficult to interpret because it could not be confirmed whether the hospitals and surgeons involved had successfully completed the learning curve. In this article we would like to present our technique, which we have developed over the past 17 years in more than 1000 patients. Based on our experiences the laparoscopic approach can be highly recommended as a suitable alternative to the open procedure. PMID- 27277557 TI - [Nutritional deficiencies and supplementation after metabolic surgery]. AB - Increasing prevalence of morbid obesity in Germany is associated with an increasing number of bariatric surgical interventions.Based on the effectiveness of bariatric surgery with regard to a significant reduction of body weight and comorbidity as well as improvement of the quality of life compared with conservative measures, its value and impact has been substantially increased. Long-term metabolic deficits such as nutrient deficiencies can be considered the main risks of various restrictive, combined and malabsorptive procedures of bariatric surgery.The aim of this overview is to characterize metabolic complications after bariatric surgery and their prophylaxis, which require a temporary or permanent surveillance and, if necessary, effective supplementation.Bariatric surgical interventions such as gastric banding (GB) and sleeve gastrectomy (SG) can be subsequently associated with deficiencies related to B-vitamins whereas iron, folate, and vitamins B1, B12 and D deficiencies might be consequences of malabsorptive procedures such as biliopancreatic diversion, duodenal switch and Roux-en-Y gastric bypass.Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life long follow-up investigations. The currently available guidelines of the American Association of Bariatric and Metabolic Surgery are the basis for the latest recommendations on supplementation and treatment in bariatric surgery. PMID- 27277559 TI - Proceedings from the Second International Conference on Physical Employment Standards - Best Practice in Physical Employment Standards: An International Perspective / Comptes rendus du deuxieme Congres international sur les normes physiques relatives a l'emploi - Pratiques exemplaires en matiere de normes physiques relatives a l'emploi : une perspective internationale. PMID- 27277558 TI - Scaling Law for Irreversible Entropy Production in Critical Systems. AB - We examine the Jarzynski equality for a quenching process across the critical point of second-order phase transitions, where absolute irreversibility and the effect of finite-sampling of the initial equilibrium distribution arise in a single setup with equal significance. We consider the Ising model as a prototypical example for spontaneous symmetry breaking and take into account the finite sampling issue by introducing a tolerance parameter. The initially ordered spins become disordered by quenching the ferromagnetic coupling constant. For a sudden quench, the deviation from the Jarzynski equality evaluated from the ideal ensemble average could, in principle, depend on the reduced coupling constant epsilon0 of the initial state and the system size L. We find that, instead of depending on epsilon0 and L separately, this deviation exhibits a scaling behavior through a universal combination of epsilon0 and L for a given tolerance parameter, inherited from the critical scaling laws of second-order phase transitions. A similar scaling law can be obtained for the finite-speed quench as well within the Kibble-Zurek mechanism. PMID- 27277560 TI - The Second International Conference on Physical Employment Standards: An International Perspective. PMID- 27277561 TI - Current considerations related to physiological differences between the sexes and physical employment standards. AB - The use of physical employment standards (PES) has helped ensure that workers have the physical attributes necessary to complete their jobs in a safe and efficient manner. However, PES used in the selection processes have not always reflected the critical physical requirements of the job tasks. Women generally have smaller anthropometric stature than men, less muscle mass, and therefore less strength, power, and endurance, particularly in the upper body. Nonetheless, these attributes in themselves are not valid grounds for exclusion from employment in physically demanding occupations. Selection standards based upon size or strength, irrespective of the job requirements, have resulted in the barring of capable women from physically demanding jobs, claims of gender bias, and costly litigations. To ensure all individuals are provided with equal access to employment, accurate characterization of the critical physical requirements of the job is paramount. This paper summarizes the existing research related to disparities between the sexes that contribute to sex differences in job performance in physically demanding occupations including physical and legal factors. Strategies for mitigating these differences in the setting of PES and the meeting of minimum employment standards are discussed. Where available, injury rates for women and men in physically demanding occupations are presented and the etiology considered. Finally, areas for further research are identified. PMID- 27277562 TI - Protective clothing ensembles and physical employment standards. AB - Physical employment standards (PESs) exist for certain occupational groups that also require the use of protective clothing ensembles (PCEs) during their normal work. This review addresses whether these current PESs appropriately incorporate the physiological burden associated with wearing PCEs during respective tasks. Metabolic heat production increases because of wearing PCE; this increase is greater than that because of simply the weight of the clothing and can vary 2 fold among individuals. This variation negates a simple adjustment to the PES for the effect of the clothing on metabolic rate. As a result, PES testing that only simulates the weight of the clothing and protective equipment does not adequately accommodate this effect. The physiological heat strain associated with the use of PCEs is also not addressed with current PESs. Typically the selection tests of a PES lasts less than 20 min, whereas the requirement for use of PCE in the workplace may approach 1 h before cooling strategies can be employed. One option that might be considered is to construct a heat stress test that requires new recruits and incumbents to work for a predetermined duration while exposed to a warm environmental temperature while wearing the PCE. PMID- 27277563 TI - Load carriage, human performance, and employment standards. AB - The focus of this review is on the physiological considerations necessary for developing employment standards within occupations that have a heavy reliance on load carriage. Employees within military, fire fighting, law enforcement, and search and rescue occupations regularly work with heavy loads. For example, soldiers often carry loads >50 kg, whilst structural firefighters wear 20-25 kg of protective clothing and equipment, in addition to carrying external loads. It has long been known that heavy loads modify gait, mobility, metabolic rate, and efficiency, while concurrently elevating the risk of muscle fatigue and injury. In addition, load carriage often occurs within environmentally stressful conditions, with protective ensembles adding to the thermal burden of the workplace. Indeed, physiological strain relates not just to the mass and dimensions of carried objects, but to how those loads are positioned on and around the body. Yet heavy loads must be borne by men and women of varying body size, and with the expectation that operational capability will not be impinged. This presents a recruitment conundrum. How do employers identify capable and injury-resistant individuals while simultaneously avoiding discriminatory selection practices? In this communication, the relevant metabolic, cardiopulmonary, and thermoregulatory consequences of loaded work are reviewed, along with concomitant impediments to physical endurance and mobility. Also emphasised is the importance of including occupation-specific clothing, protective equipment, and loads during work-performance testing. Finally, recommendations are presented for how to address these issues when evaluating readiness for duty. PMID- 27277564 TI - Thermal stress, human performance, and physical employment standards. AB - Many physically demanding occupations in both developed and developing economies involve exposure to extreme thermal environments that can affect work capacity and ultimately health. Thermal extremes may be present in either an outdoor or an indoor work environment, and can be due to a combination of the natural or artificial ambient environment, the rate of metabolic heat generation from physical work, processes specific to the workplace (e.g., steel manufacturing), or through the requirement for protective clothing impairing heat dissipation. Together, thermal exposure can elicit acute impairment of work capacity and also chronic effects on health, greatly contributing to worker health risk and reduced productivity. Surprisingly, in most occupations even in developed economies, there are rarely any standards regarding enforced heat or cold safety for workers. Furthermore, specific physical employment standards or accommodations for thermal stressors are rare, with workers commonly tested under near-perfect conditions. This review surveys the major occupational impact of thermal extremes and existing employment standards, proposing guidelines for improvement and areas for future research. PMID- 27277566 TI - Abstracts of the Second International Conference on Physical Employment Standards / Resumes scientifique de la deuxieme Congres international sur les normes physiques relatives a l'emploi. PMID- 27277565 TI - Nutra-ergonomics: influence of nutrition on physical employment standards and the health of workers. AB - The importance of ergonomics across several scientific domains, including biomechanics, psychology, sociology, and physiology, have been extensively explored. However, the role of other factors that may influence the health and productivity of workers, such as nutrition, is generally overlooked. Nutra ergonomics describes the interface between workers, their work environment, and performance in relation to their nutritional status. It considers nutrition to be an integral part of a safe and productive workplace that encompasses physical and mental health as well as the long-term wellbeing of workers. This review explores the knowledge, awareness, and common practices of nutrition, hydration, stimulants, and fortified product use employed prior to physical employment standards testing and within the workplace. The influence of these nutra ergonomic strategies on physical employment standards, worker safety, and performance will be examined. Further, the roles, responsibilities, and implications for the applicant, worker, and the employer will be discussed within the context of nutra-ergonomics, with reference to the provision and sustainability of an environment conducive to optimize worker health and wellbeing. Beyond physical employment standards, workplace productivity, and performance, the influence of extended or chronic desynchronization (irregular or shift work) in the work schedule on metabolism and long-term health, including risk of developing chronic and complex diseases, is discussed. Finally, practical nutra-ergonomic strategies and recommendations for the applicant, worker, and employer alike will be provided to enhance the short- and long-term safety, performance, health, and wellbeing of workers. PMID- 27277567 TI - Towards best practice in physical and physiological employment standards. AB - While the scope of the term physical employment standards is wide, the principal focus of this paper is on standards related to physiological evaluation of readiness for work. Common applications of such employment standards for work are in public safety and emergency response occupations (e.g., police, firefighting, military), and there is an ever-present need to maximize the scientific quality of this research. Historically, most of these occupations are male-dominated, which leads to potential sex bias during physical demands analysis and determining performance thresholds. It is often assumed that older workers advance to positions with lower physical demand. However, this is not always true, which raises concerns about the long-term maintenance of physiological readiness. Traditionally, little attention has been paid to the inevitable margin of uncertainty that exists around cut-scores. Establishing confidence intervals around the cut-score can reduce for this uncertainty. It may also be necessary to consider the effects of practise and biological variability on test scores. Most tests of readiness for work are conducted under near perfect conditions, while many emergency responses take place under far more demanding and unpredictable conditions. The potential impact of protective clothing, respiratory protection, load carriage, environmental conditions, nutrition, fatigue, sensory deprivation, and stress should also be considered when evaluating readiness for work. In this paper, we seek to establish uniformity in terminology in this field, identify key areas of concern, provide recommendations to improve both scientific and professional practice, and identify priorities for future research. PMID- 27277568 TI - Human rights at work: Physical standards for employment and human rights law. AB - This review focuses on the human rights dimensions of creating and implementing physical standards for employment for prospective and incumbent employees. The review argues that physical standards for employment engage two fundamental legal concepts of employment law: freedom of contract and workplace human rights. While the former promotes an employer's right to set workplace standards and make decisions of whom to hire and terminate, the latter prevents employers from discriminating against individuals contrary to human rights legislation. With reference to applicable human rights legislative regimes and their judicial interpretation in Canada, the United States, the United Kingdom, and Australia, this review demonstrates the judicial preference for criterion validation in testing mechanisms in the finding of bona fide occupational requirements. With particular attention to the Supreme Court of Canada decision in Meiorin, this review argues that an effective balance between workplace safety and human rights concerns can be found, not in applying different standards to different groups of individuals, but in an approach that holds employers to demonstrating a sufficient connection between a uniform physical standard of employment and the actual minimum requirements to perform the job safety and efficiently. Combined with an employer's duty to accommodate, such an approach to lawful physical standards for employment conceives of worker and public safety and workplace diversity as emanating from a shared concern for human rights. PMID- 27277569 TI - Standard-setting methodology: Establishing performance standards and setting cut scores to assist score interpretation. AB - A critical step in the development and use of tests of physical fitness for employment purposes (e.g., fitness for duty) is to establish 1 or more cut points, dividing the test score range into 2 or more ordered categories reflecting, for example, fail/pass decisions. Over the last 3 decades elaborated theories and methods have evolved focusing on the process of establishing 1 or more cut-scores on a test. This elaborated process is widely referred to as "standard-setting". As such, the validity of the test score interpretation hinges on the standard-setting, which embodies the purpose and rules according to which the test results are interpreted. The purpose of this paper is to provide an overview of standard-setting methodology. The essential features, key definitions and concepts, and various novel methods of informing standard-setting will be described. The focus is on foundational issues with an eye toward informing best practices with new methodology. Throughout, a case is made that in terms of best practices, establishing a test standard involves, in good part, setting a cut score and can be conceptualized as evidence/data-based policy making that is essentially tied to test validity and an evidential trail. PMID- 27277570 TI - Validity and reliability of physical employment standards. AB - In this paper the role of validity and reliability in the development of physical employment standards (PESs) and the consideration of these factors in determining the final pass/fail criteria for a PES and ultimately the legal defensibility of a PES is examined. Particular attention is paid to the use of subject-matter experts, the levels of evidence used in the establishment of the minimum acceptable pace/intensity for the completion of critical tasks, and the considerations needed in physical test selection. PMID- 27277571 TI - Age, human performance, and physical employment standards. AB - The proportion of older workers has increased substantially in recent years, with over 25% of the Canadian labour force aged >=55 years. Along with chronological age comes age-related declines in functional capacity associated with impairments to the cardiorespiratory and muscular systems. As a result, older workers are reported to exhibit reductions in work output and in the ability to perform and/or sustain the required effort when performing work tasks. However, research has presented some conflicting views on the consequences of aging in the workforce, as physically demanding occupations can be associated with improved or maintained physical function. Furthermore, the current methods for evaluating physical function in older workers often lack specificity and relevance to the actual work tasks, leading to an underestimation of physical capacity in the older worker. Nevertheless, industry often lacks the appropriate information and/or tools to accommodate the aging workforce, particularly in the context of physical employment standards. Ultimately, if appropriate workplace strategies and work performance standards are adopted to optimize the strengths and protect against the vulnerability of the aging workers, they can perform as effectively as their younger counterparts. Our aim in this review is to evaluate the impact of different individual (including physiological decline, chronic disease, lifestyle, and physical activity) and occupational (including shift work, sleep deprivation, and cold/heat exposure) factors on the physical decline of older workers, and therefore the risk of work-related injuries or illness. PMID- 27277572 TI - Exon skipping and aberrant signal peptide cleavage produce novel fibrinogen with an Aalpha chain lacking the first 42 residues. PMID- 27277573 TI - Effects of different forage sources as a free-choice provision on the performance, nutrient digestibility, selected blood metabolites and structural growth of Holstein dairy calves. AB - The objective of this study was to determine the effects of different forage sources on the growth performance, nutrient digestibility and blood metabolites of dairy calves. Individually housed calves (n = 40; body weight = 41.2 +/- 3.5 kg) were randomly allocated (n = 10 calves per treatment: five males and five females) to one of the following four treatments: (i) starter without forage provision (CON), (ii) starter plus chopped alfalfa hay (AH), (iii) starter plus chopped wheat straw (WS) and 4) starter plus dried sugar beet pulp (BP) flakes. Calves fed AH diets had lowest (p < 0.05) starter intake than those fed other diets, and WS promoted a significant increase (p < 0.01) in starter intake during 43-80 days. Forage intake was greatest (p < 0.01) for calves fed AH than those fed WS and BP. Calves in the AH treatment consumed less (p < 0.01) total dry matter intake than those offered other forage treatments. Final body weight was greatest (p < 0.05), and age of weaning was lowest for calves fed BP than other treatments. Calves in the BP treatment had greater (p < 0.05) average daily gain (ADG) than CON and WS treatments, but similar to AH calves. Digestibility of NDF and ADF was greater (p < 0.05) in BP treatment than other treatments. Calves fed BP had greater (p < 0.05) digestibility of DM and OM than those fed CON diets and similar to those fed AH and WS diets. Calves in the AH treatment had greater (p < 0.05) CP digestibility than CON, but similar to WS and BP calves. Blood beta hydroxybutyrate concentration was lower in forage-offered calves than CON one. Body measurements (with the exception of body barrel) did not differ across treatments. It was concluded that BP improves final body weight, ADG and nutrient digestibility of calves than starter without forage provision during weaning transition. PMID- 27277574 TI - International Journal of Paediatric Dentistry on Social Media. PMID- 27277575 TI - Biomineralization Guided by Paper Templates. AB - This work demonstrates the fabrication of partially mineralized scaffolds fabricated in 3D shapes using paper by folding, and by supporting deposition of calcium phosphate by osteoblasts cultured in these scaffolds. This process generates centimeter-scale free-standing structures composed of paper supporting regions of calcium phosphate deposited by osteoblasts. This work is the first demonstration that paper can be used as a scaffold to induce template-guided mineralization by osteoblasts. Because paper has a porous structure, it allows transport of O2 and nutrients across its entire thickness. Paper supports a uniform distribution of cells upon seeding in hydrogel matrices, and allows growth, remodelling, and proliferation of cells. Scaffolds made of paper make it possible to construct 3D tissue models easily by tuning material properties such as thickness, porosity, and density of chemical functional groups. Paper offers a new approach to study mechanisms of biomineralization, and perhaps ultimately new techniques to guide or accelerate the repair of bone. PMID- 27277576 TI - Lovastatin, but not orlistat, reduces intestinal polyp volume in an ApcMin/+ mouse model. AB - The statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and orlistat, an inhibitor of fatty acid synthase (FAS), inhibit tumor cell growth by restricting cholesterol and fatty acid synthesis, respectively. We previously demonstrated that an omega (omega)-3 polyunsaturated fatty acid (PUFA) or olive oil-enriched diet reduced the polyp number and volume in ApcMin/+ mice. This phenomenon was associated with a significant inhibition of FAS and HMGCoAR, as well as an increase in the estrogen receptor (ER)beta/alpha ratio. Herein, we evaluated the effect of lovastatin and orlistat on polyp development and ER expression in ApcMin/+ mice, in order to confirm previous data obtained with omega-3-PUFAs and olive oil. As expected, the use of lovastatin and orlistat significantly reduced HMGCoAR and FAS enzymatic activities and gene expression in colonic tissues, but did not affect the number of intestinal polyps, while there was a statistically significant reduction in polyp volume only in the mouse group treated with lovastatin. In the mice receiving orlistat, we observed a significant increase in cell proliferation in the polyp tissue, as well as enhanced expression of ERalpha. Moreover, the overexpression of ERalpha was associated with a statistically significant increase in PES1, Shh and Gli1 protein levels, considered ERalpha-related molecular targets. PMID- 27277577 TI - Connecting common genetic polymorphisms to protein function: A modular project sequence for lecture or lab. AB - Single nucleotide polymorphisms (SNPs) in DNA can result in phenotypes where the biochemical basis may not be clear due to the lack of protein structures. With the growing number of modeling and simulation software available on the internet, students can now participate in determining how small changes in genetic information impact cellular protein structure and function. We have developed a modular series of activities to engage lab or lecture students in examining the basis for common phenotypes. The activities range from basic phenotype testing/observation to DNA sequencing and simulation of protein structure and dynamics. We provide as an example study of the bitterness receptor TAS2R38 and PTC tasting, however these activities are applicable to other SNPs or genomic variants with a direct connection to an observable phenotype. These activities are modular and can be mixed to meet the student capabilities and infrastructure availability. The complete sequence of activities will demonstrate the direct connection between gene structure, protein structure and organism function. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):526 536, 2016. PMID- 27277578 TI - Phylogenetic analysis of Newcastle disease viruses isolated from commercial poultry in Mozambique (2011-2016). AB - The complete sequence of the fusion (F) protein gene from 11 Newcastle disease viruses (NDVs) isolated from commercial poultry in Mozambique between 2011 and 2016 has been generated. The F gene cleavage site motif for all 11 isolates was (112)RRRKRF(117) indicating that the viruses are virulent. A phylogenetic analysis using the full F gene sequence revealed that the viruses clustered within genotype VIIh and showed a higher similarity to NDVs from South Africa, China and Southeast Asia than to viruses previously described in Mozambique in 1994, 1995 and 2005. The identification of these new NDVs has important implications for Newcastle disease management and control in Mozambique. PMID- 27277579 TI - The Ahmed shunt versus the Baerveldt shunt for refractory glaucoma: a meta analysis. AB - BACKGROUND: The purpose of this study was to compare the efficacy and tolerability of the Ahmed glaucoma valve (AGV) implant and the Baerveldt implant for the treatment of refractory glaucoma. METHODS: We comprehensively searched four databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library databases, selecting the relevant studies. The continuous variables, namely, intraocular pressure reduction (IOPR) and a reduction in glaucoma medication, were pooled by the weighted mean differences (WMDs), and the dichotomous outcomes, including success rates and tolerability estimates, were pooled by the odds ratio (ORs). RESULTS: A total of 929 patients from six studies were included. The WMDs of the IOPR between the AGV implant and the Baerveldt implant were 1.58 [95 % confidence interval (CI): -2.99 to 6.15] at 6 months, 1.01 (95 % CI: -3.40 to 1.98) at 12 months, -0.54 (95 % CI: -4.89 to 3.82) at 24 months, and -0.47 (95 % CI: -3.29 to 2.35) at 36 months. No significant difference was detected between the two groups at any point in time. The pooled ORs comparing the AGV implant with the Baerveldt implant were 0.51 (95 % CI: 0.33 to 0.80) for the complete success rate and 0.67 (95 % CI: 0.50 to 0.91) for qualified success rate. The Baerveldt implant was associated with a reduction in glaucoma medication at -0.51 (95 % CI: -0.90 to -0.12). There were no significant differences between the AGV implant and the Baerveldt implant on the rates of adverse events. CONCLUSIONS: The Baerveldt implant is more effective in both its surgical success rate and reducing glaucoma medication, but it is comparable to the AGV implant in lowering IOP. Both implants may have comparable incidences of adverse events. PMID- 27277580 TI - Recovery of bioactive protein from bacterial inclusion bodies using trifluoroethanol as solubilization agent. AB - BACKGROUND: Formation of inclusion bodies poses a major hurdle in recovery of bioactive recombinant protein from Escherichia coli. Urea and guanidine hydrochloride have routinely been used to solubilize inclusion body proteins, but many times result in poor recovery of bioactive protein. High pH buffers, detergents and organic solvents like n-propanol have been successfully used as mild solubilization agents for high throughput recovery of bioactive protein from bacterial inclusion bodies. These mild solubilization agents preserve native-like secondary structures of proteins in inclusion body aggregates and result in improved recovery of bioactive protein as compared to conventional solubilization agents. Here we demonstrate solubilization of human growth hormone inclusion body aggregates using 30% trifluoroethanol in presence of 3 M urea and its refolding into bioactive form. RESULTS: Human growth hormone was expressed in E. coli M15 (pREP) cells in the form of inclusion bodies. Different concentrations of trifluoroethanol with or without addition of low concentration (3 M) of urea were used for solubilization of inclusion body aggregates. Thirty percent trifluoroethanol in combination with 3 M urea was found to be suitable for efficient solubilization of human growth hormone inclusion bodies. Solubilized protein was refolded by dilution and purified by anion exchange and size exclusion chromatography. Purified protein was analyzed for secondary and tertiary structure using different spectroscopic tools and was found to be bioactive by cell proliferation assay. To understand the mechanism of action of trifluoroethanol, secondary and tertiary structure of human growth hormone in trifluoroethanol was compared to that in presence of other denaturants like urea and guanidine hydrochloride. Trifluoroethanol was found to be stabilizing the secondary structure and destabilizing the tertiary structure of protein. Finally, it was observed that trifluoroethanol can be used to solubilize inclusion bodies of a number of proteins. CONCLUSIONS: Trifluoroethanol was found to be a suitable mild solubilization agent for bacterial inclusion bodies. Fully functional, bioactive human growth hormone was recovered in high yield from inclusion bodies using trifluoroethanol based solubilization buffer. It was also observed that trifluoroethanol has potential to solubilize inclusion bodies of different proteins. PMID- 27277582 TI - Erratum: First presentation of Addison's disease as hyperkalaemia in acute kidney injury. PMID- 27277581 TI - Public preferences for vaccination programmes during pandemics caused by pathogens transmitted through respiratory droplets - a discrete choice experiment in four European countries, 2013. AB - This study aims to quantify and compare preferences of citizens from different European countries for vaccination programme characteristics during pandemics, caused by pathogens which are transmitted through respiratory droplets. Internet panel members, nationally representative based on age, sex, educational level and region, of four European Union Member States (Netherlands, Poland, Spain, and Sweden, n = 2,068) completed an online discrete choice experiment. These countries, from different geographical areas of Europe, were chosen because of the availability of high-quality Internet panels and because of the cooperation between members of the project entitled Effective Communication in Outbreak Management: development of an evidence-based tool for Europe (ECOM). Data were analysed using panel latent class regression models. In the case of a severe pandemic scenario, vaccine effectiveness was the most important characteristic determining vaccination preference in all countries, followed by the body that advises on vaccination. In Sweden, the advice of family and/or friends and the advice of physicians strongly affected vaccine preferences, in contrast to Poland and Spain, where the advice of (international) health authorities was more decisive. Irrespective of pandemic scenario or vaccination programme characteristics, the predicted vaccination uptakes were lowest in Sweden, and highest in Poland. To increase vaccination uptake during future pandemics, the responsible authorities should align with other important stakeholders in the country and communicate in a coordinated manner. PMID- 27277583 TI - Acupuncture in Osgood-Schlatter disease. AB - This article describes the use of acupuncture in the management of knee pain in Osgood-Schlatter disease. Manual and electroacupuncture were used. The patient responded well to acupuncture and found it effective in relieving his knee pain. Acupuncture should be considered in Osgood-Schlatter disease, both to manage the pain and to limit the need to take oral analgaesics for a prolonged period. PMID- 27277584 TI - Spontaneous subarachnoid hemorrhage due to ruptured cavernous internal carotid artery aneurysm after medical prolactinoma treatment. AB - Aneurysms of the cavernous segment of the internal carotid artery (ICA) are believed to have a low risk of subarachnoid haemorrhage (SAH), given the confines of the dural rings and the anterior clinoid process. The risk may be greater when the bony and dural protection has been eroded. We report a case of spontaneous SAH from rupture of a cavernous ICA aneurysm in a patient whose large prolactinoma had markedly decreased in size as the result of cabergoline treatment. After passing a balloon test occlusion, the patient underwent successful endovascular vessel deconstruction. This case suggests that an eroding skull base lesion may distort normal anterior cranial base anatomy and allow communication between the cavernous ICA and subarachnoid space. The potential for SAH due to cavernous ICA aneurysm rupture should be recognised in patients with previous pituitary or other skull base lesions adjacent to the cavernous sinus. PMID- 27277585 TI - Case of migrated Gore-Tex implant following external thyroplasty. PMID- 27277586 TI - Unclassified tibial hemimelia. AB - Tibial hemimelia (congenital longitudinal deficiency of the tibia) is rare (1 in 1 000 000). There are several classifications in the literature. We report an unclassified case of tibial hemimelia. A 6-year-old girl presented with shortening of the right lower limb, with a small rudimentary foot (presence of all toes) and hyper lax ankle. Quadriceps function was excellent. Radiograph showed a partial tibia and fibula in synostosis. The Jones and Kalamachi type 2 classifications both mention similar tibial anomalies; however, the fibula is normal in both varieties. The present variety can be considered as a variant of type 2 tibial hemimelia. PMID- 27277588 TI - General ultrasound: The ichiro-type all-around diagnostician and the ichiro-type wide-fielding machine. PMID- 27277587 TI - Acute intermittent porphyria leading to posterior reversible encephalopathy syndrome (PRES): a rare cause of abdominal pain and seizures. AB - Acute intermittent porphyria (AIP) is an inherited deficiency in the haem biosynthesis pathway. AIP is rare, affecting around 1 in 75 000 people. Acute attacks are characterised by abdominal pain associated with autonomic, neurological and psychiatric symptoms. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES). PRES is a clinicoradiological condition caused by the failure of the posterior circulation to autoregulate, resulting in cerebral oedema, headaches, nausea and seizures. This association is important because drugs used in the management of seizures may worsen an attack of AIP. This article describes a case of AIP and PRES in a young woman. PMID- 27277589 TI - Qualitative diagnosis of hepatocellular carcinoma by contrast enhanced ultrasonography using Coded Harmonic Angio with Levovist. AB - We attempted to evaluate diagnosis and characterization and to access therapeutic effects in cases of hepatocellular carcinoma (HCC) by contrast enhanced ultrasound (CEUS) using Coded Harmonic Angio (CHA) with Levovist, an intravenous ultrasound contrast agent. Fifty-seven HCC foci in 39 patients, including 37 HCC foci in 28 patients before and after transcatheter arterial chemoembolization or radio frequency ablation, were examined by CEUS using the CHA mode, which is under development. This mode uses digitally encoded pulse sequences that identify and suppress nonmoving tissue signals and enhance contrast signals from Levovist in a gray-scale format. In all cases, abundant tortuous intratumoral blood flow was visualized in the early vascular phase by continuous transmission, while tumor stain was recognized by consecutive 1-to-2 second intermittent transmission. Residual tumor area after treatment was also clearly depicted by intratumoral blood flow and partial enhancement. CEUS using CHA with Levovist is likely to become important in the qualitative diagnosis of hepatic tumor and to improve the efficacy of treatment for HCC. PMID- 27277590 TI - Proximal bifurcation of hepatic artery: Novel findings on hepatic arteries demonstrated by ultrasound Doppler imaging, B-flow, and US angiography. AB - PURPOSE: It has generally been held that each portal branch is always accompanied by a single arterial branch in the liver. During Doppler ultrasound examination, however, we sometimes encounter a portal branch that appears to be associated with two arterial branches, a phenomenon referred to below asthis finding orthis phenomenon. Here we attempt to confirm that this finding is based on a correct interpretation of the image and to disclose its basic mechanism. MATERIAL AND METHODS: Five cases of chronic liver disease in which this phenomenon appeared were analyzed with B-flow imaging. Videotapes obtained from 30 patients who had chronic liver disease and had undergone ultrasound angiography (USAG) with arterial infusion of CO2 micro bubbles were reviewed in order to look for similar findings. Sixty-nine healthy controls were also examined with Doppler sonography for this purpose. Histopathologic specimens from 7 patients who had undergone hepatectomy (3 with hepatocellular carcinoma, 3 with metastatic tumor, and 1 with focal nodular hyperplasia) were examined to study the basic structure of the hepatic vessels. RESULTS AND DISCUSSION: Three parallel color signals (two pulsatile and one of a constant waveform) observed on Doppler examination were confirmed by the B-flow method to be three independent vessels in all five cases in which both Doppler sonography and B-flow imaging were used. In 13 (43%) of the 30 cases of USAG, two vessels along a portal branch were visualized by the inflow of micro bubbles, indicating that the two vessels were arteries. The trio of one portal and two arterial branches was also detected with Doppler sonography in 12 (17%) of the 69 healthy controls. In 10 (59%) of the 17 cases (5 of liver disease and 12 normal) that showed this finding on Doppler examination, bifurcations of the hepatic artery and portal vein were both visualized. Hepatic arterial branches were found to bifurcate slightly more proximal to the hepatic hilus than the accompanying portal branch. Histopathologic study revealed Glisson's areas that contained one portal branch and two arterial vessels in nontumorous parts of specimens from all 7 patients with hepatectomy. CONCLUSION: Two arterial branches can be demonstrated along a portal branch as a result of a more-proximal bifurcation of the hepatic artery than of the portal vein. PMID- 27277591 TI - A case of Fitz-Hugh-Curtis syndrome: Thickening of the lateroconal fascia and posterior renal fascia. AB - We encountered a case of Fitz-Hugh-Curtis syndrome. Ultrasonography and computed tomography revealed a thickening of the lateroconal fascia and posterior renal fascia. These fasciae might be sensitive, although not specific, markers for this entity. PMID- 27277592 TI - Diagnosis of arteriovenous malformation of the internal iliac vessels by color Doppler ultrasonography: A case report. AB - A 13-year-old girl was admitted to the hospital because of cardiomegaly found incidentally at regular medical checkup at her school. Although dilated cardiomyopathy was suspected, the girl showed no symptoms. chest x-ray film showed cardiomegaly (cardiothoracic ratio, 67%), and echocardiogram demonstrated a dilatation of the left ventricle without thinning of the wall. While contraction was diffusely decreased, estimated cardiac output was increased to 13l/minute. Abdominal ultrasonography conducted to clarify the cause of this high output showed a multicystic lesion (8*6*4 cm) at the back of the left common iliac artery. Color Doppler ultrasonography revealed abundant blood flow within the lesion, establishing the diagnosis of arteriovenous malformation. Aortography delineated the arteriovenous malformation being supplied from the left internal iliac artery and from the left third and fourth lumbar arteries and drainage into the left common iliac vein and the right internal iliac vein. Although it did not show the precise location of the feeding and draining vessels, color Doppler ultrasonography was useful for the diagnosis of arteriovenous malformation. PMID- 27277593 TI - Ultrasonographic features of polypoid myoglandular hyperplasia of the gallbladder, that were difficult to distinguish from early gallbladder cancer. AB - The patient, a 50-year-old man, had been followed up by a neurologist under the diagnosis of mitochondrial encephalomyopathy. A gallstone detected by abdominal ultrasonography (US) had been present for several years, but localized protrusions of the gallbladder wall were first seen at the fundus in May 1995. Endoscopic US after abdominal US showed several small protruding lesions with maximum diameters of about 7 mm. These lesions had irregular surfaces and low internal echogenicity. An external high echoic layer, which represented the subserosa of the gallbladder, was intact. The lesions were enhanced on CT scanning. No anomalies of the pancreaticobiliary system were detected by endoscopic retrograde cholangiopancreatography. Selective cystic arteriography disclosed slight staining of the body of the gallbladder. Because of the high possibility of gallbladder carcinoma, surgery was carried out. Macroscopy showed several elevated or protruding lesions up to 7 mm in diameter at the fundus of the resected gallbladder. The lesions had rough surfaces and were yellowish in color. Histologic examination showed the lesions to be covered by columnar epithelium, and no cellular dysplasia was detected. Because both pyloric gland like hyperplasia and smooth-muscle proliferation were observed, the lesions were diagnosed as polypoid myoglandular hyperplasia. We have encountered four other similar cases of this tumor. Accurate diagnosis of these lesions before surgery is sometimes difficult, and the sonographic features of myoglandular hyperplasia have to be recognized in order to distinguish it from early gallbladder cancer. PMID- 27277595 TI - The AP2-type transcription factors DORNROSCHEN and DORNROSCHEN-LIKE promote G1/S transition. AB - The paralogous genes DORNROSCHEN (DRN) and DORNROSCHEN-LIKE (DRNL) encode AP2 type transcription factors that are expressed and act cell-autonomously in the central stem-cell zone or lateral organ founder cells (LOFCs) in the peripheral zone of the Arabidopsis shoot meristem (SAM), but their molecular contribution is unknown. Here, we show using the Arabidopsis thaliana MERISTEM LAYER 1 promoter that DRN and DRNL share a common function in cell cycle progression and potentially provide local competence for G1-S transitions in the SAM. Analysis of double transgenic DRN::erGFP and DRNL::erCERULEAN promoter fusion lines suggests that the trajectory of this cellular competence starts with DRN activity in the central stem-cell zone and extends locally via DRNL activity into groups of founder cells at the IM or FM periphery. Our data support the scenario that after gene duplication, DRN and DRNL acquired different transcription domains within the shoot meristem, but retained protein function that affects cell cycle progression, either centrally in stem cells or peripherally in primordial founder cells, a finding that is of general relevance for meristem function. PMID- 27277596 TI - A Review of the Key Clinical Trials of 2015: Results and Implications. AB - INTRODUCTION: Multiple significant, potentially practice changing clinical trials in cardiology have been conducted and subsequently presented throughout the past year. METHODS: In this paper, the authors have reviewed and contextualized significant cardiovascular clinical trials presented at major international conferences of 2015 including American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, American Diabetes Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Rhythm Congress, and the American Heart Association Scientific Sessions. RESULTS: The authors describe new trial data for heart failure (including eplerenone, finerenone, patiromer, sacubitril/valsartan, the beta 3 agonist mirabegron, sitagliptin, empagliflozin, alginate-hydrogel LV epicardial implant), anticoagulation (idarucizumab and andexanet alfa reversal agents, adherence programmes, practice in ablation), transcatheter aortic valve replacement (long-term data, valve-in-valve use, the TriGuard embolic deflecting device), patent foramen ovale closure, cardiovascular prevention (PCSK9 inhibitors, hypertension treatment) and antiplatelets strategies (extended duration therapy with clopidogrel or ticagrelor). Trial data are also described for contemporary technologies including the Biofreedom polymer-free drug coated stent, bioabsorbable stents, PCI strategies, left main treatment, atrial fibrillation ablation techniques, leadless pacemakers and the role of coronary computed tomographic angiography. CONCLUSIONS: This paper summarizes and contextualizes multiple pertinent 2015 clinical trials and will be of interest to both clinicians and cardiology researchers. PMID- 27277597 TI - Ultrastructural regenerating features of nasal mucosa following microdebrider assisted turbinoplasty are related to clinical recovery. AB - BACKGROUND: The nasal mucosa plays a key role in conditioning the inhaled air and in regulating the immune response. These functions led many authors to recommend mucosal sparing techniques for the surgical management of inferior turbinate hypertrophy. However, the histological modifications of chronic diseases retain the inflammatory activity and prevent the nasal physiology restoration. It has been proved that the basal cells of the nasal mucosa are able to proliferate and to repair after cold-knife incision. The aim of this study was to demonstrate that the healing process after removal of the inferior turbinate mucosa with cold techniques results in a complete structural restoration. METHODS: A prospective study was performed in 18 patients who underwent Microdebrider inferior turbinoplasty (cold technique). Subjective and objective improvement of nasal patency was evaluated with visual analogue scale, rhinomanometry, videoendoscopy and mucociliary transport test. Pre- and post-operative biopsy specimens were taken from 7 patients to evaluate the healing process. Two samples were taken from two healthy patients as control. The specimens were processed for transmission electron microscopy analysis. RESULTS: Videoendoscopy showed reduction of lower turbinate after surgery. Nasal patency augmented and no adverse consequences were observed. After 4 months the nasal mucosa showed normal appearance, with restoration of the pseudostratified ciliated pattern, intercellular connections and normal cellular morphology. Fibrosis and submucosal edema disappeared. At longer time after operation (4 years) clinical improvement was confirmed. CONCLUSIONS: The total removal of the nasal mucosa with cold techniques results in a complete restoration of the normal structure and permanent resolution of the chronic inflammation typical of hypertrophic rhinopathy. PMID- 27277598 TI - Healthcare providers on the frontlines: a qualitative investigation of the social and emotional impact of delivering health services during Sierra Leone's Ebola epidemic. AB - Although research on the epidemiology and ecology of Ebola has expanded since the 2014-15 outbreak in West Africa, less attention has been paid to the mental health implications and the psychosocial context of the disease for providers working in primary health facilities (rather than Ebola-specific treatment units). This study draws on 54 qualitative interviews with 35 providers working in eight peripheral health units of Sierra Leone's Bo and Kenema Districts. Data collection started near the height of the outbreak in December 2014 and lasted 1 month. Providers recounted changes in their professional, personal and social lives as they became de facto first responders in the outbreak. A theme articulated across interviews was Ebola's destruction of social connectedness and sense of trust within and across health facilities, communities and families. Providers described feeling lonely, ostracized, unloved, afraid, saddened and no longer respected. They also discussed restrictions on behaviors that enhance coping including attending burials and engaging in physical touch (hugging, handshaking, sitting near, or eating with colleagues, patients and family members). Providers described infection prevention measures as necessary but divisive because screening booths and protective equipment inhibited bonding or 'suffering with' patients. To mitigate psychiatric morbidities and maladaptive coping mechanisms-and to prevent the spread of Ebola-researchers and program planners must consider the psychosocial context of this disease and mechanisms to enhance psychological first aid to all health providers, including those in peripheral health settings. PMID- 27277599 TI - Is it possible to stop follow-up of patients with primary T1G3 urothelial carcinoma of the bladder managed with intravesical bacille Calmette-Guerin immunotherapy? AB - BACKGROUND: Recurrence and progression of T1 grade 3 (T1G3) urothelial bladder carcinomas (UBCs) treated with bacille Calmette-Guerin (BCG) are common events, but the long-term follow-up of the disease remains controversial. OBJECTIVE: To evaluate the long-term outcomes of BCG intravesical therapy in relation to disease recurrence and progression in primary T1G3 UBCs and upper tract disease. PATIENTS AND METHODS: A single-institution, retrospective, population-based analysis of 316 patients with primary T1G3 UBC treated with transurethral resection (TUR) and BCG induction intravesical instillations was performed. Response was determined and monitored by routine periodic urine cytology, cystoscopy, and upper tract imaging. RESULTS: The median follow-up was 70 months (maximum 210 months). Among all of the tumours, 49.4 % did not relapse, 48.7 % recurred in the bladder during the first 5 years of surveillance, and only 6 patients (1.9 %) recurred after being free of disease during the first 5 years of follow-up. Nineteen percentage of the UBCs progressed to stage T2, and only 2 patients (1.2 %) progressed after the first 5 years of surveillance. An upper urinary tract recurrence was detected in 9.2 % of the patients; 65.5 % were diagnosed within the upper urinary tract during the first 5 years of follow-up. CONCLUSIONS: Following a 5-year tumour-free period, there is minimal risk of recurrence and progression in T1G3 UBCs treated with TUR and BCG induction intravesical instillations. This finding supports a less intensive and potentially less invasive surveillance scheme of bladder follow-up and upper urinary tract imaging in patients without any recurrence. PMID- 27277602 TI - Electronic journals and reprint requests. PMID- 27277603 TI - Hypotonia-induced cell swelling enhances ultrasound-induced mechanical damage to cancer cells. AB - INTRODUCTION: It has been shown that killing of suspended cells by low-intensity ultrasound (0.08-0.11 W/cm(2)) can be enhanced by a mild non-lethal hypotonic (146 mOsm) medium. PURPOSE: In this study we wished to determine whether hypotonia-induced cell swelling of suspension cells was directly related to enhancement of ultrasound-mediated cell killing, and to verify whether similar effects could be observed on circulating and attached cells. METHODS: U937 cells under mild hypotonia were exposed to ultrasound for different times with real time monitoring of cell size using a particle-size-distribution analyzer. To study the effect on attached cells, HeLa cells were exposed to ultrasound while under hypotonia in an in vivo-simulated set-up. RESULTS: The result showed that the enhanced cell killing (up to more than twice) was directly proportional to hypotonia-induced cell swelling. Similar membrane damage based on PI staining could be observed on HeLa cells treated with hypotonia. An in vivo-simulated circulating system also showed similar findings for hypotonia-enhanced ultrasound cell killing. CONCLUSION: These findings showed that mild hypotonia can be used to augment the effect of ultrasound in the treatment of cancers, particularly leukemia. The results showing that such enhancement is related to cell swelling could guide us toward proper timing of sonication while under hypotonic treatment. PMID- 27277601 TI - Socioeconomic determinants of childhood obesity among primary school children in Guangzhou, China. AB - BACKGROUND: Socioeconomic inequalities in childhood obesity prevalence differ according to a country's stage of nutrition transition. The aim of this study was to determine which socioeconomic factors influence inequalities in obesity prevalence in Chinese primary school children living in an urban setting. METHODS: We assessed obesity prevalence among 9917 children aged 5-12 years from a stratified random sample of 29 state-funded (residents) and private (migrants) schools in Guangzhou, China. Height and weight were objectively measured using standardised methods and overweight (+1 SD < BMI-for-age z-score <= +2 SD) and obesity (BMI-for-age z-score > +2 SD) were defined using the World Health Organisation reference 2007. Socioeconomic characteristics were ascertained through parental questionnaires. Generalised Linear Mixed Models with schools as a random effect were used to compare likelihood of overweight/obesity among children in private, with public schools, adjusting for child age and sex, maternal and paternal BMI and education level, and household per-capita income. RESULTS: The prevalence of overweight/obesity was 20.0 % (95 % CI 19.1 %-20.9 %) in resident compared with 14.3 % (95 % CI 13.0 %-15.4 %) in migrant children. In the adjusted model, the odds of overweight/obesity remained higher among resident children (OR 1.36; 1.16-1.59), was higher in boys compared with girls (OR 2.56; 2.24-2.93), and increased with increasing age (OR 2.78; 1.95-3.97 in 11-12 vs 5-6 year olds), per-capita household income (OR 1.27; 1.01-1.59 in highest vs lowest quartile) and maternal education (OR 1.51; 1.16-1.97 in highest vs lowest). Socioeconomic differences were most marked in older boys, and were only statistically significant in resident children. CONCLUSIONS: The socioeconomic gradient for childhood obesity in China is the reverse of the patterns seen in countries at more advanced stages of the obesity epidemic. This presents an opportunity to intervene and prevent the onset of social inequalities that are likely to ensue with further economic development. The marked gender inequality in obesity needs further exploration. PMID- 27277600 TI - Systemic therapy in metastatic renal cell carcinoma. AB - PURPOSE: Current systemic treatment of targeted therapies, namely the vascular endothelial growth factor-antibody (VEGF-AB), VEGF receptor tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitors, have improved progression-free survival and replaced non-specific immunotherapy with cytokines in metastatic renal cell carcinoma (mRCC). METHODS: A panel of experts convened to review currently available phase 3 data for mRCC treatment of approved agents, in addition to available EAU guideline data for a collaborative review as the plurality of substances offers different options of first-, second- and third-line treatment with potential sequencing. RESULTS: Sunitinib and pazopanib are approved treatments in first-line therapy for patients with favorable- or intermediate-risk clear cell RCC (ccRCC). Temsirolimus has proven benefit over interferon-alfa (IFN-alpha) in patients with non-clear cell RCC (non ccRCC). In the second-line treatment TKIs or mTOR inhibitors are treatment choices. Therapy options after TKI failure consist of everolimus and axitinib. Available third-line options consist of everolimus and sorafenib. Recently, nivolumab, a programmed death-1 (PD1) checkpoint inhibitor, improved overall survival benefit compared to everolimus after failure of one or two VEGFR targeted therapies, which is likely to become the first established checkpoint inhibitor in mRCC. Data for the sequencing of agents remain limited. CONCLUSIONS: Despite the high level of evidence for first and second-line treatment in mRCC, data for third-line therapy are limited. Possible sequences include TKI-mTOR-TKI or TKI-TKI-mTOR with the upcoming checkpoint inhibitors in perspective, which might settle a new standard of care after previous TKI therapy. PMID- 27277604 TI - Ultrasonography for ureteral stone detection in patients with or without caliceal dilatation. AB - PURPOSE: To evaluate the relationship between the degree of hydronephrosis and the detection rates of ureteral stones with ultrasonography (US). METHODS: Of 250 consecutive patients with suspected ureterolithiasis, 214 who were diagnosed with ureterolithiasis were enrolled in this study. First, both kidneys were observed by US to evaluate the intrarenal collecting systems. Thereafter, the possible course of the ureters and the bladder were searched to find any stones. RESULTS: Stones were clearly observed in 80 (73%) of 109 patients with caliceal dilatation, whereas stones were clearly observed in 46 (44%) of 105 patients without dilatation (P < 0.05). Of the former 80 patients, 31 (39%) had stones in the ureterovesical junction (UVJ), whereas 51 (64%) had stones in the more proximal ureter. Of the latter 46 patients, 37 (80%) had stones in the UVJ or the bladder, whereas 9 (20%) had stones in the more proximal ureter. CONCLUSION: The US detection rate of ureteral stones was high in patients with caliceal dilatation. The whole ureter should be scanned in patients with caliceal dilatation for detection of ureteral stones. Even when patients have no caliceal dilatation, it is still considered to be useful to scan the UVJ and the bladder. PMID- 27277605 TI - Use of intraoperative ultrasonography to monitor surgery for large acoustic neuromas: a pilot study. AB - PURPOSE: Operations for large acoustic neuromas were difficult. The aim of this pilot study was to determine whether intraoperative ultrasonography (IOUS) was a useful adjunct to the microsurgery. METHODS: Fifteen patients with large acoustic neuromas underwent surgical interventions. IOUS was applied in seven cases, and the other eight cases served as controls. IOUS was performed to monitor the surgery, and the intraoperative data were compared with postoperative CT/MRI scans. RESULTS: All tumors could be identified in ultrasonic images. Lesions appeared as solid (2/7) or mixed patterns (5/7) with clear boundaries. A larger tumor volume was seen in the IOUS group but without statistical significance (29.05 +/- 15.47 vs. 21.82 +/- 14.78 cm(3), P = 0.3718). The use of IOUS did not prolong the operation time (404.29 +/- 111.18 vs. 420.00 +/- 114.24 min, P = 0.7921) and did not increase the rate of intracranial infections (28.57 vs. 25.00%, P = 1.000). The residual tumor detected with IOUS immediately after the operation was consistent with the data from postoperative CT/MRI scans in all cases. CONCLUSION: IOUS can be used to monitor surgery in real time as a technique to assist microsurgical procedures for large acoustic neuromas with trouble. PMID- 27277606 TI - Painful hepatic hemangioma: report of a case with an emphasis on sonographic findings. AB - Hepatic hemangiomas are usually asymptomatic and very rarely produce abdominal symptoms. We report a painful 10 * 9 cm hemangioma situated at the hepatic surface of segment 6. The lesion showed a heterogeneous internal structure, composed irregularly of hyperechoic and hypoechoic areas, and it also showed weak posterior echo enhancement. Contrast-enhanced US showed the so-called fill-in pattern, leading to the diagnosis of hepatic hemangioma. The patient's abdomen showed no other abnormal findings, which stressed the relationship between the hemangioma and the patient's symptoms. When the diagnosis of hepatic hemangioma is conclusive, surgical therapy is indicated only in patients with severe symptoms. Our patient was considered to be a candidate for enucleation of the lesion. Histopathologically, the lesion included no areas of hemorrhage or necrosis, and the patient's abdominal pain was likely due to distension of the liver capsule. After surgery, the patient was completely free of symptoms, and enucleation was considered to be appropriate. PMID- 27277607 TI - Pleomorphic adenoma originating from the trachea showing the appearance of a follicular tumor of the thyroid on ultrasonography. AB - Pleomorphic adenoma (PA) is the most common tumor of the salivary gland. This report presents a case of a PA originating from the trachea that looked like a thyroid neoplasm on ultrasonography, showing a well-circumscribed, hypovascular, solid, and hypoechoic tumor within the thyroid. The tumor was resected with the right lobe of the thyroid and the first tracheal ring, which revealed a PA impacted within the thyroid. PAs originating outside of the salivary glands are rare, and there have been no reports of PAs arising from the lateral side of the trachea. This report describes the first reported, and unique, case of this type of tumor. PMID- 27277608 TI - Ultrasonographic findings in epiploic appendagitis. PMID- 27277609 TI - High-output heart failure caused by renal arteriovenous fistula. PMID- 27277610 TI - Erratum to: Bladder neck evaluation by perineal ultrasound before and after reconstructive surgery for pelvic organ prolapse. PMID- 27277611 TI - Technological innovations in medicine and health care, and restoration of trust. PMID- 27277612 TI - Confirmation of enhanced expression of heme oxygenase-1 gene induced by ultrasound and its mechanism: analysis by cDNA microarray system, real-time quantitative PCR, and Western blotting. AB - PURPOSE: The present study was undertaken to reconfirm heme oxygenase-1 (HO-1) induction by ultrasound, and elucidate the mechanism by which this occurs. METHODS: After exposure of human lymphoma U937 cells to 1 MHz continuous ultrasound (US), gene profiling by using cDNA microarray analysis, cell viability by using the trypan blue dye exclusion test, mRNA expression by using real-time quantitative polymerase chain reaction, and protein expression by using Western blotting were examined. As an indicator of cavitation, hydroxyl radical formation was studied by using electron paramagnetic resonance-spin trapping. RESULTS: The cDNA microarray analysis reconfirmed HO-1 induction in human lymphoma U937 cells after exposure to US, and further identified one upregulated and two downregulated genes. When U937 cells were exposed to US for 1 min, HO-1 induction, as examined by real-time quantitative polymerase chain reaction and Western blotting, was observed at intensities higher than the cavitational threshold. When a potent antioxidant, N-acetyl-L-cysteine, was added to the culture medium before or after sonication, the induction was attenuated, indicating that reactive oxygen species are involved in HO-1 induction. A decrease in mitochondrial membrane potential and generation of superoxide anion radicals were also observed in the cells exposed to US. CONCLUSION: We used a cDNA microarray system to confirm upregulation of the HO-1 gene and to discover new genes that respond to ultrasonic cavitation. Increased intracellular oxidative stress secondary to the sonomechanical effects arising from ultrasonic cavitation is suggested to be the mechanism of enhancement of HO-1 expression. PMID- 27277613 TI - Analysis of refractive artifacts by reconstructed three-dimensional ultrasound imaging. AB - PURPOSE: Refractive artifacts are frequently encountered in clinical settings, and they have been analyzed on the basis of conventional two-dimensional (2-D) ultrasound (US) images, but this method is restricted to monoplane data and is limited by its inability to assess the three-dimensional (3-D) structure of refractive artifacts. The aim of this study was to evaluate the role of reconstructed 3-D US images in the analysis of refractive artifacts. METHODS: The following representative refractive artifacts were analyzed on the basis of reconstructed 3-D US images: (a) a distorted image of a fine tube behind a cyst (balloon); (b) a deformed image of the bottom of a balloon; and (c) a duplication artifact due to the acoustic lens effect. RESULTS: (a) A tube was imaged as a fine echogenic line with two points of sudden interruption, unlike a curved needle, which was imaged without interruption. (b) 3-D US allowed us to visualize the mode of deformity in the image of the bottom of a fluid-filled balloon in a water bath. When the acoustic velocity in the fluid was greater than that in the surrounding water, the bottom of the balloon appeared to be shrunken. When the acoustic velocity in the fluid was less than that in the surrounding water, the bottom of the balloon appeared to be swollen. (c) When we placed two pieces of white chicken meat in front of a fine needle, the needle was duplicated in the resulting image. In this case, the needle appeared to be vague and fuzzy. In this case, 3-D US did not add further information to the 2-D images. CONCLUSIONS: Our study suggests that reconstructed 3-D US images provide a better understanding of the mode of refractive artifacts than do 2-D US images. PMID- 27277614 TI - Low-dose dobutamine stress echocardiography predicts the improvement of left ventricular systolic function and long-term prognosis in patients with idiopathic dilated cardiomyopathy. AB - PURPOSE: It is unclear whether left ventricular (LV) contractile reserve assessed by low-dose dobutamine stress echocardiography (DSE) can predict the long-term prognosis together with LV functional changes in patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Contractile reserve was determined in 28 patients with DCM, and was then compared with changes in LV fractional shortening (FS) and cardiac events during a follow-up period of 68 +/- 43 months. Nine events (2 sudden deaths, 5 heart failure deaths, and 2 rehospitalizations for heart failure) were observed. FS at peak dose was lower in patients with events (events group) than in those without events (no-events group) (20 +/- 6 vs. 27 +/- 7%; P < 0.05), although there were no differences in FS at baseline between the two groups. FS at follow-up was lower in the events group than in the no-events group (14 +/- 7 vs. 21 +/- 8%; P < 0.05). The change in FS during DSE (FS at peak dose/baseline) correlated with the change in FS during the follow-up time (FS at follow-up/baseline), and it was a predictor of events by multiple regression analysis. CONCLUSIONS: LV contractile reserve assessed by low-dose DSE is a useful marker not only to predict LV functional improvement, but also to determine the long-term prognosis in patients with DCM. PMID- 27277615 TI - Identification of stimulation site of pacemaker lead using tissue tracking method. AB - PURPOSE: We aimed to identify the electrical stimulation sites of pacemaker leads using a tissue tracking method of tissue Doppler imaging. METHODS: The study group consisted of 30 patients who had undergone permanent pacemaker implantation. During tissue Doppler imaging, the initial contraction site was seen as a red area stimulated by the pacemaker lead. This red area was analyzed precisely using time-distance curves generated by tissue tracking. RESULTS: The initial contraction site of the myocardium was located in the interventricular septum in seven patients and in the apical portion of the right ventricle in 11 patients. Furthermore, analysis of time-distance curves demonstrated that one point within the red area started to move earlier than the others. CONCLUSION: The site of electrical stimulation within the myocardium can be determined from the time-distance curves generated by the tissue tracking method. PMID- 27277616 TI - Contrast-enhanced sonography of pancreatic ductal carcinoma using agent detection imaging. AB - PURPOSE: The aim of this study was to evaluate the enhancement behavior of pancreatic ductal carcinoma by contrast-enhanced sonography with agent detection imaging (ADI), and to clarify the origin of microbubble signals by comparisons with histological findings of resected specimens. METHODS: The subjects were 21 patients with resectable pancreatic carcinoma. The final histological diagnosis was tubular adenocarcinoma in 20 cases, and anaplastic carcinoma in one case. Ultrasound examinations were performed using an Acuson Sequoia 512 series system, and the contrast agent (Levovist) was injected intravenously in doses of 7 ml (300 mg/ml). The ADI signals (in the tumor) were recorded continuously for 30 s after an injection of Levovist (vascular image) and then obtained intermittently (30 s time-intervals) until the signal had diminished in pancreatic tissue (perfusion image). RESULTS: Contrast enhancement of the tumor was observed in 71.4% of subjects on the vascular image and 76.3% of subjects on the perfusion image. Enhancement patterns on the vascular image were classified into three types: VI-1 (linear enhancement), VI-2 (spotty enhancement), and VI-3 (no enhancement). VI-1, VI-2, and VI-3 were seen in 9 (42.8%), 6 (28.6%), and 6 (28.6%) of the 21 cases, respectively. Enhancement patterns on the perfusion image were classified into four types: PI-1 (diffuse uneven enhancement), PI-2 (spotty enhancement), PI-3 (peripheral enhancement), and PI-4 (negative enhancement). The incidence of PI-1, PI-2, PI-3, and PI-4 was 4.8%, 42.9%, 28.6%, and 23.8%, respectively. With respect to resectable cases, these enhancement patterns were compared with histological findings, i.e., the distribution of blood vessels in the tumor, remaining pancreatic tissues in the tumor, differentiation of types of adenocarcinoma, volume of stroma, and invasion types of carcinoma. The enhanced patterns consequently corresponded to either the distribution of the blood vessels or the remaining pancreatic tissues in the tumor. CONCLUSION: This study indicated that pancreatic ductal carcinoma is frequently enhanced by microbubbles, and the signals seem to originate from fine blood vessels and the remaining pancreatic tissues in the tumor. PMID- 27277617 TI - Sonographic findings of transvaginal color Doppler ultrasound in ectopic pregnancy. AB - PURPOSE: The objective of this study was to retrospectively assess whether the sonographic findings from transvaginal color Doppler ultrasound (TV-CDU) are helpful in the diagnosis of ectopic pregnancy. METHODS: Thirty-four patients who received surgery for ectopic tubal pregnancies were preoperatively evaluated using TV-CDU. The presence or absence of color vascularity within the ectopic masses was examined. The relationship between the presence or absence of blood flow in the tubal mass and the corpus luteum cyst, or the serum beta-hCG values, was evaluated. RESULTS: Color vascularity within the adnexal mass was detected in 27 of 34 (79.4%) patients with ectopic pregnancies by TV-CDU. Color vascularity within the mass was observed in 18 of 24 (75.0%) patients with a questionable adnexal mass that had no obvious gestational sac in B-mode images. Moreover, color vascularity was seen in all four patients with a serum beta-human chorionic gonadotropin (beta-hCG) value of less than 500 mIU/ml. However, it was difficult to identify the blood flow of the adnexal mass in six of the nine (66.7%) patients with a corpus luteum cyst in the ipsilateral ovary. No relationship was observed between the serum beta-hCG concentrations and the resistance indices, or the peak systolic velocity. CONCLUSIONS: The detection of color vascularity by TV CDU in patients with an ectopic pregnancy is helpful for diagnosis, especially for patients with either a questionable adnexal mass in B-mode images or lower serum beta-hCG concentrations. PMID- 27277618 TI - Three-dimensional sonographic measurement of fetal renal volume. AB - OBJECTIVE: The objective of this longitudinal study was to evaluate the growth of the fetal kidney in normal pregnancies using three-dimensional ultrasound. METHODS: Three-dimensional sonographic examinations were performed on 13 appropriate-for-gestational-age fetuses. Fetal renal volume was measured every 2 to 3 weeks after 20 weeks gestational age until delivery. RESULTS: There was a good linear correlation between left and right renal volumes (r = 0.9614, P < 0.0001). Curvilinear relationships were found between gestational age and left and right renal volume (left: R(2) = 79.1%, P < 0.0001; right: R(2) = 74.2%, P < 0.0001), and normal ranges of left and right renal volume measurements for estimating the growth of the fetal kidney during normal pregnancy were generated. There was a difference for each predicted value of the fetal renal volume in the third trimester of pregnancy in our study and in two other previous studies. The left and right fetal renal volume to estimated fetal weight ratios were constant during the pregnancies studied. CONCLUSION: Our findings suggest that fetal renal volume measurement plays a role in assessment of the growth of fetal kidneys. However, we are doubtful about the reproducibility of fetal renal volume measurements made by using three-dimensional ultrasound in utero. Further studies involving larger sample sizes are needed to reevaluate the usefulness and reproducibility of fetal renal volume measurements. PMID- 27277619 TI - Nodular fascitis in the thigh followed up using ultrasonography. AB - A 41-year-old woman noticed a mass on the inside of her right thigh in April 2003. Ultrasound examination revealed a mass measuring 18 mm * 10 mm * 10 mm in the subcutaneous fatty tissues. Its boundary was relatively clear, with rough edges. The interior of the lesion was hyperechoic and contained an irregular hypoechoic area in its center; a color Doppler sonographic examination detected no blood flow signals. Incision biopsy examination seemed warranted. Pathologically, the specimen showed a proliferation of fibroblast-like spindle shaped cells but no atypical cells. Immunologic staining revealed that sections were positive to vimentin; negative to CD34, CD68, alpha-smooth muscle actin (alpha-SMA), and S-100 protein; and mildly positive to HHF35. These results led to a diagnosis of nodular fascitis. Nodular fascitis is not common, and few studies have described its sonographic characteristics. We therefore used ultrasound to follow up the patient and found that the lesion was markedly smaller 3 months after the first examination, at which time it was hardly discernible as a mass. Here we compare the ultrasound and pathologic findings, and report the results of a bibliographic study. PMID- 27277620 TI - Prevalence of biliary ascariasis and its relation to biliary lithiasis. AB - Hepatobiliary ultrasound was carried out on 2224 consecutive patients at the Center for Nuclear Medicine and Ultrasound and at one private diagnostic center in Mymensingh for ultrasound examination of different systems. The purpose of this study was to investigate the prevalence of biliary ascariasis and its association with other biliary diseases, specially biliary lithiasis. Data regarding the presence of stone, worm or other diseases were recorded accordingly in this prospective study. There were 952 male and 1272 female patients with an age range of 5-90 years. Biliary diseases were detected in 305 patients (13.71%), of whom 97 were male (10.19%) and 208 were female (16.35%). The most common biliary disease in both sexes was cholelithiasis (11.87%), which was found in 84 male patients (8.82%) and in 180 female patients (14.15%). Other diseases found were choledocholithiasis in 14 patients (3 males, 11 females), gall bladder mass in 9 patients (3 males, 6 females), common bile duct mass in 7 patients (4 male, 3 female) and biliary ascariasis in 10 patients (3 male, 7 female). Overall prevalence of biliary ascariasis was 0.45% (0.31% in male patients and 0.55% in female patients), and age range of patients with the condition was 6-50 years. No case of biliary ascariasis was associated with cholelithiasis or choledocholithiasis. Acute cholecystitis was associated with 8 cases (80%) of biliary ascariasis. Common sonographic findings in patients with biliary ascariasis were a single long, linear or curved echogenic structure within the bile duct, without acoustic shadowing. Other findings were gall bladder distention with sludge inside, an edematous wall and mildly dilated biliary tree. Prevalence of biliary ascariasis in the study was 0.45%, with incidence being higher in female subjects (0.55%). No correlation was found between biliary ascariasis and biliary lithiasis. Most of the cases of biliary ascariasis were associated with acute cholecystitis. We concluded that a careful search for biliary ascariasis should be considered for patients with acute acalculus cholecystitis, especially in areas in which ascariasis is endemic, such as Bangladesh. PMID- 27277621 TI - The value of intraoperative ultrasonography in neurosurgery. AB - Intraoperative ultrasonography is widely used in neurosurgery today. Here we attempt to clarify and demonstrate its usefulness in the operating room. Of 113 lesions, 112 were detected during surgery. The undetected lesion was a spinal arachnoid hematoma that had been absorbed during an intraoperative maneuver. No infection or complication occurred after surgery. Ultrasound guidance ensures safe tumor removal by minimizing injury to cerebral tissue and shortening operation time. Intraoperative ultrasonography improves the safety and efficiency of neurosurgery. PMID- 27277622 TI - When the gallbladder is not detected in the usual location. PMID- 27277623 TI - Implication of advanced glycation end products (Ages) and their receptor (Rage) on myocardial contractile and mitochondrial functions. AB - Advanced glycation end products (AGEs) play an important role for the development and/or progression of cardiovascular diseases, mainly through induction of oxidative stress and inflammation. AGEs are a heterogeneous group of molecules formed by non-enzymatic reaction of reducing sugars with amino acids of proteins, lipids and nucleic acids. AGEs are mainly formed endogenously, while recent studies suggest that diet constitutes an important exogenous source of AGEs. The presence and accumulation of AGEs in various cardiac cell types affect extracellular and intracellular structure and function. AGEs contribute to a variety of microvascular and macrovascular complications through the formation of cross-links between molecules in the basement membrane of the extracellular matrix and by engaging the receptor for advanced glycation end products (RAGE). Activation of RAGE by AGEs causes up regulation of the transcription factor nuclear factor-kappaB and its target genes. of the RAGE engagement stimulates oxidative stress, evokes inflammatory and fibrotic reactions, which all contribute to the development and progression of devastating cardiovascular disorders. This review discusses potential targets of glycation in cardiac cells, and underlying mechanisms that lead to heart failure with special interest on AGE induced mitochondrial dysfunction in the myocardium. PMID- 27277625 TI - Differential Associations of Religious Involvement with the Mental Health of Asian-American Subgroups: A Cultural Perspective. AB - In the USA, Asian-Americans (AA) constitute the fastest growing ethnic minority group, in which heterogeneous religious patterns and acculturation experiences can impose significant impacts on their mental health. Using national data, the present study examined the contributions of religious involvement and social support to self-rated mental health (SRMH) of Chinese, Vietnamese, and Filipinos. Findings demonstrated cross-group variations, with Filipinos reporting the highest levels of SRMH, acculturation, and discrimination. However, religious involvement was associated with better SRMH in the least religious Chinese subgroup but not in the most religious Filipino subgroup. Social support predicted SRMH for both Chinese and Vietnamese subgroups. The differential religious patterns in the more acculturated generations between the two AA subgroups suggest religious assimilation as part of their acculturation in the context of divergent immigration experiences. PMID- 27277626 TI - Expectations for contrast-enhanced ultrasonography. PMID- 27277624 TI - Genetic Dissection of the Signaling Cascade that Controls Activation of the Shigella Type III Secretion System from the Needle Tip. AB - Many Gram-negative bacterial pathogens use type III secretion systems (T3SSs) for virulence. The Shigella T3SS consists of a hollow needle, made of MxiH and protruding from the bacterial surface, anchored in both bacterial membranes by multimeric protein rings. Atop the needle lies the tip complex (TC), formed by IpaD and IpaB. Upon physical contact with eukaryotic host cells, T3S is initiated leading to formation of a pore in the eukaryotic cell membrane, which is made of IpaB and IpaC. Through the needle and pore channels, further bacterial proteins are translocated inside the host cell to meditate its invasion. IpaD and the needle are implicated in transduction of the host cell-sensing signal to the T3S apparatus. Furthermore, the sensing-competent TC seems formed of 4 IpaDs topped by 1 IpaB. However, nothing further is known about the activation process. To investigate IpaB's role during T3SS activation, we isolated secretion-deregulated IpaB mutants using random mutagenesis and a genetic screen. We found ipaB point mutations in leading to defects in secretion activation, which sometimes diminished pore insertion and host cell invasion. We also demonstrated IpaB communicates intramolecularly and intermolecularly with IpaD and MxiH within the TC because mutations affecting these interactions impair signal transduction. PMID- 27277627 TI - Ex vivo evaluation of high-intensity focused ultrasound with ultrasonic-induced cavitation bubbles. AB - PURPOSE: In high-intensity focused ultrasound (HIFU) comprising high-intensity burst ultrasound (triggering pulse) and medium-intensity continuous wave ultrasound (heating wave), optimizing the effects of the triggering pulse conditions on the coagulated volume may help to reduce treatment times. METHODS: HIFU combined with a triggering pulse was applied to chicken deep pectoral muscles. The acoustic power of the heating wave was set to 36, 54, or 72 W. Four different triggering pulse conditions were used: heating wave only; or pulse widths and pulse repetition frequencies of 30 MUs and 1 kHz, 300 MUs, and 100 Hz, or 3 ms and 10 Hz. RESULTS: Compared to the heating wave only condition, the coagulated volume was significantly larger under all conditions that included a triggering pulse. Significant differences were also observed in the ellipticity of the coagulated region between some conditions. CONCLUSION: HIFU combined with a triggering pulse may play an important role in reducing treatment times. PMID- 27277629 TI - Experimental verification of color flow imaging based on wideband Doppler method. AB - The purpose of this study is to eliminate the aliasing in color flow imaging. The wideband Doppler method is applied to generate a color flow image, and the validity of the method is experimentally confirmed. The single beam experiment is carried out to confirm the velocity estimation based on the wideband Doppler method. The echo data for the conventional pulsed Doppler method and the wideband Doppler method are obtained using a flow model, and the estimated velocity for each method is compared. The color flow images for each method are also generated using several types of flow model. The generated images are compared, and the characteristics of the imaging based on the wideband Doppler method are discussed. The high velocity beyond the Nyquist limit is successfully estimated by the wideband Doppler method, and the availability in low velocity estimation is also confirmed. The aliasing in color flow images is eliminated, and the generated images show the significance of the elimination of the aliasing in the flow imaging. The aliasing in color flow imaging can be eliminated by the wideband Doppler method. This technique is useful for the exact understanding of blood flow dynamics. PMID- 27277628 TI - Ultrasound image-guided therapy enhances antitumor effect of cisplatin. AB - PURPOSE: The aim of this study was to clarify whether ultrasound image-guided cisplatin delivery with an intratumor microbubble injection enhances the antitumor effect in a xenograft mouse model. METHODS: Canine thyroid adenocarcinoma cells were used for all experiments. Before in vivo experiments, the cisplatin and microbubble concentration and ultrasound exposure time were optimized in vitro. For in vivo experiments, cells were implanted into the back of nude mice. Observed by a diagnostic ultrasound machine, a mixture of cisplatin and ultrasound contrast agent, Sonazoid, microbubbles was injected directly into tumors. The amount of injected cisplatin and microbubbles was 1 MUg/tumor and 1.2 * 10(7) microbubbles/tumor, respectively, with a total injected volume of 20 MUl. Using the same diagnostic machine, tumors were exposed to ultrasound for 15 s. The treatment was repeated four times. RESULTS: The combination of cisplatin, microbubbles, and ultrasound significantly delayed tumor growth as compared with no treatment (after 18 days, 157 +/- 55 vs. 398 +/- 49 mm(3), P = 0.049). Neither cisplatin alone nor the combination of cisplatin and ultrasound delayed tumor growth. The treatment did not decrease the body weight of mice. CONCLUSION: Ultrasound image-guided anticancer drug delivery may enhance the antitumor effects of drugs without obvious side effects. PMID- 27277630 TI - Normal values of liver elasticity measured by real-time tissue elastography (RTE) in healthy infants and children. AB - PURPOSE: To define normal values of liver elasticity measured by real-time tissue elastography (RTE) in healthy infants and children. METHODS: RTE was performed on 91 children and adolescents by two experienced observers (female, n = 43; male, n = 48) and in two age groups (0-10 years, n = 45; 11-20 years, n = 46). Hepatopathies were excluded clinically by extensive laboratory testing and by ultrasound. RTE provides a histogram from a region of interest (ROI) in the liver representing the degree of stiffness of the liver. The distribution of the colors in the histogram corresponds to organ elasticity. By calculating the mean of stiffness values, a numerical value is expressed in arbitrary units (a.u.) representing the mean elasticity of the liver (MEAN). Additionally, the percentage values of relatively stiffer areas (color coded in blue) in the ROI can be calculated (%AREA). A Mann-Whitney U test was performed for these two parameters according to gender. The reproducibility of these values was determined with an intraclass correlation coefficient (ICC) test on another group of 18 healthy volunteers. RESULTS: The median elasticity was 106 a.u. Gender did not have an influence on the parameters (MEAN: p = 0.052; %AREA: p = 0.051). Age specific analyses did not yield any significant difference between the two age groups for either of the two analyzed parameters (MEAN: p = 0.059; %AREA: p = 0.058). The ICC test demonstrated a moderate agreement for MEAN (ICC = 0.582) and %AREA (ICC = 0.659). CONCLUSION: Real-time elastography is a new sonography-based method and may be used as a supportive analysis to assess liver parenchyma elasticity in children, especially when fibrosis is suspected. We measured RTE normal values in children as reference data. PMID- 27277631 TI - Breast US in patients with breast cancer presenting as only microcalcifications on mammography: can US differentiate ductal carcinoma in situ from invasive cancer? AB - PURPOSE: To retrospectively review sonographic findings of breast cancers presenting as only microcalcifications on mammography and to evaluate factors essential for differentiating ductal carcinoma in situ (DCIS) from invasive cancers. METHODS: We retrospectively reviewed the medical records of 620 consecutive patients with confirmed breast cancer according to surgery performed between March 2008 and October 2011 at our institution. Of these, 53 lesions from 52 patients who had only microcalcifications without a mass or other associated findings on mammography were selected. Sonographic findings of microcalcification areas were analyzed and correlated with the histopathological findings. RESULTS: Of the 53 lesions, 26 (49.18 %) were classified as invasive cancer and 27 (50.9 %) as DCIS. Ultrasonography (US) showed only echogenic calcifications in five (9.4 %), calcifications within hypoechoic parenchymal thickening in 14 (26.4 %), calcifications within ductal changes in three (5.7 %), and calcifications within a mass in 14 (26.4 %). Seventeen (32.1 %) lesions were not visible on US. Negative findings in US were more frequently observed for DCIS (n = 15, 55.6 %) than for invasive cancers (n = 2, 7.7 %) (p < 0.001). Masses (n = 11, 42.3 % of invasive cancer; n = 3, 11.1 % of DCIS; p = 0.01) were more frequently observed in invasive cancers than in DCIS. CONCLUSIONS: US findings of breast cancers presenting as only mammographic microcalcifications were significantly different between DCIS and invasive cancers. Targeted US of microcalcifications might be helpful for predicting invasive cancers and for determining the clinical preoperative work-up, including axillary staging. PMID- 27277632 TI - Significance of septa in first trimester increased nuchal translucency thickness. AB - PURPOSE: The objective of this study was to investigate perinatal outcome in cases of increased nuchal translucency (NT) with or without cystic hygroma (CH), and to determine whether first-trimester CH engenders a greater risk than simple increased NT. METHODS: In this retrospective study, data from singleton pregnancies in which fetal NT was found to be 3 mm or more at the 11 + 0 to 13 + 6 weeks scan were reviewed. Cases were classified into two groups, namely 'CH' and 'increased NT'. RESULTS: Of the 76 cases with increased NT, 30 (39.4 %) presented with CH. NT measurement was significantly higher in the CH group (7.25 vs. 3.5 mm, p < 0.001). Abnormal fetal karyotype, major chromosomal anomalies in chromosomally normal fetuses, and adverse outcome were significantly more frequent in the CH group as compared with the increased NT group (p = 0.019, p = 0.021, and p = 0.001, respectively). Regression analysis revealed that NT thickness was the only significant variable in the prediction of chromosomal defect and/or major congenital anomaly (OR 2.05, 95 % CI 1.23-3.42, p = 0.005). CONCLUSION: Cystic hygroma results in poorer outcome due to higher NT measurement, and the thickness of NT rather than the presence of septa should be the mainstay of prenatal counseling in cases of increased NT in the first trimester. PMID- 27277633 TI - High-frequency ultrasound findings in epididymal malformations. AB - PURPOSE: This work aims to investigate high-frequency ultrasound findings in epididymal malformations and their clinical significance. METHODS: Eighty-five of 9,849 patients who had been examined using high-frequency ultrasound for infertility, varicocele, scrotal swelling, and so on had epididymal malformations. A retrospective analysis was conducted on the ultrasound findings of epididymal malformations in these 85 patients. RESULTS: There were a total of 117 malformed epididymides in 85 patients with epididymal malformations. The detection rate of epididymal malformations using high-frequency ultrasound was 0.86 % (85/9,849). CONCLUSIONS: High-frequency ultrasound can be used to diagnose epididymal malformation and seminiferous duct blockage. PMID- 27277634 TI - Acceleration time ratio for the assessment of extracranial internal carotid artery stenosis. AB - PURPOSE: To apply the acceleration time (AcT) ratio as an additional marker for diagnosing internal carotid artery (ICA) stenosis. METHODS: Carotid artery sonography was performed in 140 patients, and the AcT ratio was calculated as the AcT of the ICA divided by the AcT of the ipsilateral common carotid artery, and compared with diameter stenosis. RESULTS: There was a significant correlation between diameter stenosis and the AcT ratio. The receiver operating characteristic curve revealed a cutoff level of 1.5, with 90.0 % sensitivity and 93.5 % specificity for stenosis >65 %. CONCLUSION: Our results indicate that applying the AcT ratio can help in the diagnosis of ICA stenosis. PMID- 27277636 TI - A case of arrhythmogenic right ventricular cardiomyopathy in a 70-year-old patient. AB - A 70-year-old man was admitted because of syncope and dyspnea. Two months before admission, exertional dyspnea occurred with syncope. Ventricular tachycardia with a monomorphic left bundle-branch block configuration was detected. An echocardiographic examination showed severe dilatation and diffuse, severe hypokinesis of the right ventricle, with thrombus formation in the right ventricular apex. Based on the clinical picture, the patient was diagnosed with arrhythmogenic right ventricular cardiomyopathy (ARVC). This case emphasizes the need for early identification of RV abnormalities in patients with ARVC to determine appropriate therapy. PMID- 27277635 TI - Massive tricuspid regurgitation due to pacemaker-lead puncture of the tricuspid valve: successful diagnosis by 3-dimensional echocardiography. AB - An 83-year-old woman presented to our echocardiographic center with symptoms of right heart failure. A dual-chamber DDDR pacemaker had been implanted 9 years earlier. Two-dimensional echocardiography revealed right atrial and ventricular enlargement and massive tricuspid regurgitation with immobilization of the anterior leaflet of the tricuspid valve. Three-dimensional transesophageal echocardiography showed that the pacemaker lead had punctured the leaflet. These echocardiographic findings were confirmed during surgery. The pacemaker lead was transected and removed, and pericardial patch closure of the leaflet hole and tricuspid annuloplasty were performed. The mechanism of regurgitation was elucidated by real-time three-dimensional echocardiography, and surgical repair was straightforward. PMID- 27277637 TI - Ileocecal, colonic, and peritoneal tuberculosis: role of imaging in diagnosis. A case report and literature review. AB - Tuberculosis is a widespread infectious disease that still remains a deadly global health problem and a condition that is life-threatening if misdiagnosed. Extrapulmonary manifestations are prevalent in the endemic areas but limited to the immunocompromised and immigrants in economically developed areas. False diagnostic situations rely on non-specific investigatory findings, the wide spectrum of clinical manifestations, and problems in discriminating between inflammation and neoplasms of the bowel. For an early diagnosis, a high index of suspicion and correlation of clinical and imaging aspects, as well as findings from colonoscopy, tissue biopsy, and microbiologic assessments, are necessary. We present a case of a patient with non-specific abdominal symptoms, mimicking a clinical syndrome of neoplastic impregnation, finally diagnosed as ileal tuberculosis with peritoneal involvement. We stress the importance of ultrasonography as a primary method of investigation, having an important role in raising the suspicion of an infectious bowel disease, as well as the role of contrast-enhanced ultrasound examination. PMID- 27277638 TI - Spontaneously infarcted fibroadenoma of the breast in an adolescent girl: sonographic findings. AB - Spontaneous infarction in fibroadenoma unrelated to any known risk factors is extremely rare. Here, I present a case of a spontaneously infarcted fibroadenoma in an adolescent girl in whom no plausible predisposing factors were identified. High-resolution sonographic imaging showed a unique circumscribed, complex echoic mass containing a frondular solid portion. PMID- 27277639 TI - Role of ultrasonography in detection of renal artery pseudoaneurysm caused by retroperitoneal malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1. AB - Malignant peripheral nerve sheath tumors (MPNSTs) are extremely uncommon neoplasms, predominantly seen within the deep soft tissues of the extremities, in close proximity to the nerve trunks. Retroperitoneal MPNSTs are exceedingly rare, usually seen in association with neurofibromatosis type 1 (NF-1), and often result from malignant degeneration of a plexiform neurofibroma. These tumors are highly malignant and the prognosis is worsened if they occur in association with NF-1. Metastasis is not uncommon, but local invasion by these tumors is rarely reported. Renal artery pseudoaneurysms are mostly iatrogenic and rarely result from invasion by retroperitoneal neoplasms. Ultrasonography is a valuable tool in early diagnosis of these neoplasms and vascular complications, particularly in emergency cases requiring immediate operative intervention. To the best of our knowledge, no case of renal artery pseudoaneurysm caused by retroperitoneal MPNST has been reported to date. We present a case of a middle-aged female with Von Recklinghausen disease, complaining of sudden onset of severe abdominal pain, where ultrasound accurately diagnosed renal artery pseudoaneurysm caused by a large retroperitoneal MPNST, and who was later treated by radical excision of the tumor and nephrectomy. PMID- 27277640 TI - Epididymal lymphoma: report of two cases and imaging findings. AB - Epididymal lymphoma is a very rare tumor that is difficult to differentiate radiologically from other paratesticular tumors. Most cases of epididymal lymphoma are secondary involvement of the epididymis in patients with testicular lymphoma. However, isolated epididymal lymphoma is very rare. We herein report two cases of isolated epididymal lymphoma with different imaging findings. Patient 1 was a 52-year-old man who presented with a painless scrotal mass. Patient 2 was a 65-year-old man who presented with painless scrotal swelling. Ultrasound (US) demonstrated different imaging findings: US in patient 1 showed a well-defined round mass in the tail of the epididymis with hypervascularity confined to the epididymis, while US in patient 2 showed diffuse infiltrative enlargement with hypervascularity confined to the epididymis. Orchiectomy performed in both patients revealed diffuse large B-cell lymphoma confined to the epididymis. PMID- 27277641 TI - Microcalcifications in the breast detected by a color Doppler method using twinkling artifacts: some important discussions based on clinical cases and experiments with a new ultrasound modality called multidetector-ultrasonography (MD-US). AB - The twinkling artifact is well known as a color Doppler artifact but it is still an unresolved phenomenon [Rahmouni et al., Radiology 1996;199:269-271 ; Atan et al., Astas Urol Esp 2001;35:396-402; Kamaya et al., AJR 2003;80:215-222]. Many factors affect the appearance of the twinkling artifact, such as the surface roughness of stones creating multiple reflections and a form of intrinsic noise known as clock jitter within the Doppler circuitry of the ultrasound equipment. However, no studies have reported on the twinkling artifact of breast microcalcifications. While considering these premises, I detected microcalcifications in the breast using twinkling artifacts that could not be detected on B-mode imaging. The twinkling artifact is a well-defined but not well understood phenomenon that may assist in the detection of calcified foci. The phenomenon of the twinkling artifact is discussed here with regard to prospectively and retrospectively studied cases including experiments with a new ultrasound modality called multidetector-ultrasonography (MD-US). MD-US using detectability of the twinkling artifact in microcalcifications of the breast may play an important role in breast screening. PMID- 27277642 TI - HDlive rendering image of cyclopia and a proboscis in a fetus with normal chromosomes at 32 weeks of gestation. PMID- 27277643 TI - Sonographically guided puncture of pancreatic lesions: a low number of needle passes does not compromise the diagnostic yield. PMID- 27277644 TI - Ultrasound diagnostic criteria for hepatic tumors. PMID- 27277645 TI - Differential diagnosis of dialysis-associated renal cell carcinoma with ultrasonography. PMID- 27277646 TI - Fetal venous blood flow pattern reference ranges (2013). PMID- 27277647 TI - New blood pressure goals for patients with increased cardiovascular risk. PMID- 27277648 TI - In this issue July 2016. PMID- 27277649 TI - Pediatric anesthesia editorial-propofol and remifentanil: to mix or not to mix. PMID- 27277650 TI - Anesthesia for muscle biopsy: when nothing bad happened, was no special care needed? PMID- 27277651 TI - Symptomatic endotracheal tube obstruction in infants intubated with Microcuff((r)) endotracheal tubes. PMID- 27277652 TI - ABC Diaphragmatic Evaluation for neonates. PMID- 27277653 TI - Reply to Ideno, Satoshi; Seki, Hiroyuki; Morisaki, Hiroshi, regarding their comment 'Consider an additional pressure-relief port before we abandon the use of the wall oxygen through a bronchoscope'. PMID- 27277654 TI - Response to comment 'Tsui, Ban; Tsui, Jenkin: ABC diaphragmatic evaluation for neonates'. PMID- 27277655 TI - A call to solve the puzzle together by building an evidence base for perioperative management of children with autism spectrum disorder. PMID- 27277656 TI - Correspondence Letter to the Editor regarding 'The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex' by Langley, McFadzean & McCormack. PMID- 27277657 TI - Bubble induction. PMID- 27277659 TI - Impact of neutrophil-to-lymphocyte ratio on periprocedural myocardial infarction in patients undergoing non-urgent percutaneous coronary revascularisation. AB - BACKGROUND: Pro-thrombotic conditions importantly influence myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). The neutrophil-to-lymphocyte ratio (NLR) has emerged as a predictor of cardiovascular events and of long-term prognosis, especially in ST-elevation myocardial infarction patients undergoing primary PCI. The aim of our study was to evaluate the role of NLR on periprocedural myocardial infarction (MI) in patients undergoing non-urgent PCI. METHODS: In a consecutive cohort of 1542 patients undergoing PCI, myonecrosis biomarkers were determined at 6, 12, 24 and 48 hours post-procedure. Patients were divided into quintiles according to NLR values. Periprocedural myonecrosis was defined as a troponin I increase of 3 times the upper limit of normal or as 50 % of an elevated baseline value, whereas periprocedural MI was defined as a CK-MB increase of 3 times the upper limit of normal or 50 % of baseline. RESULTS: Higher NLR was related to age, established risk factors and cardiovascular history. NLR was associated with severe coronary artery disease (p = 0.009), tighter stenosis (p < 0.001), coronary calcifications (p = 0.005), intracoronary thrombus or thrombectomy use (p < 0.001), TIMI flow pre- and post-PCI (p < 0.001), and inversely to restenosis (p = 0.04) and use of a drug-eluting stent (p = 0.001). NLR did not influence the occurrence of myonecrosis (p = 0.75; adjusted OR (95 % CI) = 0.99 (0.63-1.54), p = 0.96), but was associated with a higher occurrence of periprocedural MI, even after correction for baseline differences (p = 0.03; adjusted OR (95 % CI) = 1.33 (1.02 2.3), p = 0.02), with NLR >= 3 best predicting the risk of periprocedural MI at the receiver operating characteristic curve analysis. CONCLUSION: In patients undergoing non-urgent PCI, a higher NLR increases the risk of periprocedural MI, especially for values >= 3. PMID- 27277660 TI - Improvement in Glucose Control in Difficult-to-Control Patients With Diabetes Using a Novel Flash Glucose Monitoring Device. PMID- 27277658 TI - G-quadruplex RNA binding and recognition by the lysine-specific histone demethylase-1 enzyme. AB - Lysine-specific histone demethylase 1 (LSD1) is an essential epigenetic regulator in metazoans and requires the co-repressor element-1 silencing transcription factor (CoREST) to efficiently catalyze the removal of mono- and dimethyl functional groups from histone 3 at lysine positions 4 and 9 (H3K4/9). LSD1 interacts with over 60 regulatory proteins and also associates with lncRNAs (TERRA, HOTAIR), suggesting a regulatory role for RNA in LSD1 function. We report that a stacked, intramolecular G-quadruplex (GQ) forming TERRA RNA (GG[UUAGGG]8UUA) binds tightly to the functional LSD1-CoREST complex (Kd ~ 96 nM), in contrast to a single GQ RNA unit ([UUAGGG]4U), a GQ DNA ([TTAGGG]4T), or an unstructured single-stranded RNA. Stabilization of a parallel-stranded GQ RNA structure by monovalent potassium ions (K(+)) is required for high affinity binding to the LSD1-CoREST complex. These data indicate that LSD1 can distinguish between RNA and DNA as well as structured versus unstructured nucleotide motifs. Further, cross-linking mass spectrometry identified the primary location of GQ RNA binding within the SWIRM/amine oxidase domain (AOD) of LSD1. An ssRNA binding region adjacent to this GQ binding site was also identified via X-ray crystallography. This RNA binding interface is consistent with kinetic assays, demonstrating that a GQ-forming RNA can serve as a noncompetitive inhibitor of LSD1-catalyzed demethylation. The identification of a GQ RNA binding site coupled with kinetic data suggests that structured RNAs can function as regulatory molecules in LSD1-mediated mechanisms. PMID- 27277661 TI - Antagonist wear of monolithic zirconia crowns after 2 years. AB - OBJECTIVES: The aim of this study was to evaluate the amount of wear on the antagonist occlusal surfaces of clinically placed monolithic zirconia premolar and molar crowns (LAVA Plus, 3M ESPE). MATERIALS AND METHODS: Fourteen in situ monolithic zirconia crowns and their opposing antagonists (n = 26) are the subject of an ongoing clinical trial and have been clinically examined at baseline and after 24 months. Silicone impressions were taken and epoxy replicas produced for qualitative SEM analysis and quantitative analysis using optical profilometry. Based on the baseline replicas, the follow-up situation has been scanned and digitally matched with the initial topography in order to calculate the mean volume loss (in mm3) as well as the mean maximum vertical loss (in mm) after 2 years in service. RESULTS: The mean volume loss for enamel antagonist contacts (n = 7) was measured to 0.361 mm3 and the mean of the maximum vertical loss to 0.204 mm. The mean volume loss for pure ceramic contacts (n = 10) was measured to 0.333 mm3 and the mean of the maximum vertical loss to 0.145 mm. The wear rates on enamel contacts were not significantly different from those measured on ceramic antagonists. CONCLUSIONS: Based on the limitations of this study, it can be concluded for the monolithic zirconia material LAVA Plus that the measured wear rates are in consensus with other in vivo studies on ceramic restorations. Further, that no significant difference was found between natural enamel antagonists and ceramic restorations as antagonists. The monolithic zirconia restorations do not seem to be affected by wear within the first 2 years. CLINICAL RELEVANCE: The monolithic zirconia crowns (LAVA Plus) show acceptable antagonist wear rates after 2 years in situ, regardless of natural enamel or ceramics as antagonist materials. PMID- 27277663 TI - Nine-Year Follow-up in a Child with Antenatally Diagnosed Hepatoblastoma. PMID- 27277662 TI - Event-related potentials reflecting smoking cue reactivity and cognitive control as predictors of smoking relapse and resumption. AB - RATIONALE: Given that most attempts to quit smoking fail, it is critical to increase knowledge about the mechanisms involved in smoking relapse and resumption (i.e., the increase in smoking over time after a quit attempt). Neurocognitive measures, such as event-related potentials (ERPs), may provide novel insights into smoking relapse and resumption. OBJECTIVES: The objective of the present study is to investigate the association between smoking relapse and resumption and ERPs reflecting smoking cue reactivity (i.e., P300, LPP), inhibitory control (i.e., N2, P3), and error processing (i.e., error-related negativity (ERN), Pe). METHODS: Seventy-two smokers viewed smoking and neutral pictures and performed a Go-NoGo and an Eriksen Flanker task, while ERPs were measured using electroencephalography. All smokers started a quit attempt in the week following the laboratory visit. Smoking behavior after the quit attempt was measured at 4, 8, and 12 weeks. Both relapse (i.e., 7-day point prevalence at 12 weeks) and smoking resumption (i.e., the number of cigarettes a day at 4, 8, and 12 weeks) were used as outcome measures. RESULTS: Logistic regression analyses showed that smaller P3 amplitudes, reflecting brain activation associated with inhibitory control, are related to an increased relapse risk. Latent growth curve analyses showed that reduced post-error slowing, the main behavioral measure reflecting error processing, is associated with stronger smoking resumption. ERPs reflecting smoking cue reactivity were unrelated to smoking relapse or resumption. CONCLUSIONS: The finding that smaller inhibitory control-related P3 amplitudes are associated with increased relapse risks suggests that strategies to increase inhibitory control in smokers are worth further investigation in the search for more effective smoking cessation interventions. PMID- 27277664 TI - Primary Follicular Lymphoma of the Gastrointestinal Tract: Case Report and Review. AB - PURPOSE: Primary gastrointestinal follicular lymphoma (GI-FL) is considered a rare disease with fewer than 400 cases reported in the literature. It accounts for roughly 1-3 % of GI non-Hodgkins lymphomas (NHL). It originates in the GI tract and typically affects small bowel. The disease has an indolent course, and a prolonged survival can be expected in most cases. Due to its rarity, an optimal diagnostic work up and treatment plan has not been well established. METHODS: Endoscopic evaluation of the entire gastrointestinal (GI) tract using esophagogastroduodenoscopy (EGD), wireless capsule endoscopy, double-balloon enteroscopy, colonoscopy, and whole body examination with fluorodeoxyglucose positron emission tomography (FDG-PET) has been suggested to more accurately stage the disease and guide the treatment plan. RESULTS: Treatment options for GI follicular lymphoma include watch and wait strategy, surgery, chemotherapy, radiation, immuno-radiotherapy, or a combination of these modalities. CONCLUSION: In this article, we have summarized the existing information regarding clinical presentation, diagnostic evaluation, and treatment options for this rare entity after presenting a case of GI-FL who was diagnosed during an EGD for evaluation of belching, heartburn, and weight loss. PMID- 27277666 TI - New blood test could personalise depression treatment. PMID- 27277665 TI - Genetic risk factors for restenosis after percutaneous coronary intervention in Kazakh population. AB - BACKGROUND: After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population. METHODS: Four hundred fifty-nine patients were recruited to the study; 91 patients were also diagnosed with diabetes and were excluded from the sampling. DNA was extracted with the salting-out method. The patients were genotyped for 53 single-nucleotide polymorphisms. Genotyping was performed on the QuantStudio 12K Flex (Life Technologies). Differences in distribution of BMI score among different genotype groups were compared by analysis of variance (ANOVA). Also, statistical analysis was performed using R and PLINK v.1.07. Haplotype frequencies and LD measures were estimated by using the software Haploview 4.2. RESULTS: A logistic regression analysis found a significant difference in restenosis rates for different genotypes. FGB (rs1800790) is significantly associated with restenosis after stenting (OR = 2.924, P = 2.3E-06, additive model) in the Kazakh population. CD14 (rs2569190) showed a significant association in the additive (OR = 0.08033, P = 2.11E-09) and dominant models (OR = 0.05359, P = 4.15E-11). NOS3 (rs1799983) was also highly associated with development of restenosis after stenting in additive (OR = 20.05, P = 2.74 E-12) and recessive models (OR = 22.24, P = 6.811E-10). CONCLUSIONS: Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results. PMID- 27277668 TI - ALD/MLD processes for Mn and Co based hybrid thin films. AB - Here we report the growth of novel transition metal-organic thin-film materials consisting of manganese or cobalt as the metal component and terephthalate as the rigid organic backbone. The hybrid thin films are deposited by the currently strongly emerging atomic/molecular layer deposition (ALD/MLD) technique using the combination of a metal beta-diketonate, i.e. Mn(thd)3, Co(acac)3 or Co(thd)2, and terephthalic acid (1,4-benzenedicarboxylic acid) as precursors. All the processes yield homogeneous and notably smooth amorphous metal-terephthalate hybrid thin films with growth rates of 1-2 A per cycle. The films are stable towards humidity and withstand high temperatures up to 300 or 400 degrees C under an oxidative or a reductive atmosphere. The films are characterized with XRR, AFM, GIXRD, XPS and FTIR techniques. PMID- 27277671 TI - Physiological and comparative proteome analyses reveal low-phosphate tolerance and enhanced photosynthesis in a maize mutant owing to reinforced inorganic phosphate recycling. AB - BACKGROUND: The low-phosphate-tolerant maize mutant Qi319-96 was obtained from Qi319 through cellular engineering. To elucidate the molecular mechanisms underlying the low-phosphate tolerance of this mutant, we performed comparative proteome analyses of the leaves of Qi319-96 and Qi319 under inorganic phosphate (Pi)-sufficient and Pi-deficient conditions. RESULTS: Low-phosphorus levels limit plant growth and metabolism. Although the overall phosphorus contents of shoots were not significantly different between Qi319 and Qi319-96, the Pi level of Qi319-96 was 52.94 % higher than that of Qi319. Under low phosphorus conditions, Qi319-96 had increased chlorophyll levels and enhanced photosynthesis. The changes in starch and sucrose contents under these conditions also differed between genotypes. The proteomic changes included 29 (Pi-sufficient) and 71 (Pi deficient) differentially expressed proteins involved in numerous metabolic processes. Proteome and physiological analyses revealed that Qi319-96 could better remodel the lipid composition of membranes and had higher V-ATPase activity levels than Qi319 under low-phosphate starvation, which enhanced the recycling of intracellular Pi, as reflected by its increased Pi levels. Chlorophyll biosynthesis was improved and the levels, and activities, of several Calvin cycle and "CO2 pump" enzymes were greater in Qi319-96 than in Qi319, which led to a higher rate of photosynthesis under low-phosphate stress in this line compared with in Qi319. CONCLUSIONS: Our results suggest that the increased tolerance of the maize mutant Qi319-96 to low-phosphate levels is owing to its ability to increase Pi availability. Additionally, inbred lines of maize with low P-tolerant traits could be obtained effectively through cellular engineering. PMID- 27277672 TI - Source and risk factors of a cutaneous anthrax outbreak, Jiangsu, Eastern China, 2012. AB - Anthrax is still a severe public health problem and threat to human health. A cutaneous anthrax outbreak occurred in Jiangsu Province, a non-endemic anthrax region of eastern China, from July to August 2012. Epidemiological and laboratory investigation were initiated to trace the source of infection and identify the risk factors of the outbreak. On 25 July 2012, 17 persons were exposed to a sick cow, which had been imported from northeast China a few days previously. Of the 17 exposed, eight developed symptoms between 1 and 8 days and were diagnosed as cutaneous anthrax cases. Three main genes of Bacillus anthracis were detected from both human and cow meat samples, indicating that the outbreak was associated with this infected cow. A retrospective cohort study showed that contact with blood and presence of skin damage contributed to the case infection with B. anthracis. The outbreak highlights the need to enhance quarantine for imported livestock, which should have been vaccinated prior to importation, the significance of education for high-risk individuals, and training for primary healthcare workers even in anthrax-free areas. PMID- 27277673 TI - Accumulation of human full-length tau induces degradation of nicotinic acetylcholine receptor alpha4 via activating calpain-2. AB - Cholinergic impairments and tau accumulation are hallmark pathologies in sporadic Alzheimer's disease (AD), however, the intrinsic link between tau accumulation and cholinergic deficits is missing. Here, we found that overexpression of human wild-type full-length tau (termed hTau) induced a significant reduction of alpha4 subunit of nicotinic acetylcholine receptors (nAChRs) with an increased cleavage of the receptor producing a ~55kDa fragment in primary hippocampal neurons and in the rat brains, meanwhile, the alpha4 nAChR currents decreased. Further studies demonstrated that calpains, including calpain-1 and calpain-2, were remarkably activated with no change of caspase-3, while simultaneous suppression of calpain 2 by selective calpain-2 inhibitor but not calpain-1 attenuated the hTau-induced degradation of alpha4 nAChR. Finally, we demonstrated that hTau accumulation increased the basal intracellular calcium level in primary hippocampal neurons. We conclude that the hTau accumulation inhibits nAChRs alpha4 by activating calpain-2. To our best knowledge, this is the first evidence showing that the intracellular accumulation of tau causes cholinergic impairments. PMID- 27277674 TI - Surgeons' exposure to sevoflurane during paediatric adenoidectomy: a comparison of three airway devices. AB - Although sevoflurane is commonly used in anaesthesia, a threshold value for maximum exposure to personnel does not exist and although anaesthetists are aware of the problem, surgeons rarely focus on it. We used a photo-acoustic infrared device to measure the exposure of surgeons to sevoflurane during paediatric adenoidectomies. Sixty children were randomly allocated to laryngeal mask, cuffed tracheal tube or uncuffed tracheal tube. The average mean (maximum) sevoflurane concentrations within the surgeons' operating area were 1.05 (10.05) ppm in the laryngeal mask group, 0.33 (1.44) ppm in the cuffed tracheal tube group and 1.79 (18.02) ppm in the uncuffed tracheal tube group, (p < 0.001), laryngeal mask and cuffed tracheal tube groups vs. uncuffed tube group. The presence of sevoflurane was noticed by surgeons in 20% of cases but there were no differences between the groups (p = 0.193). Surgical and anaesthetic complications were similar in all three groups. We conclude that sevoflurane can be safely used during adenoidectomies with all three airway devices, but in order to minimise sevoflurane peak concentrations, cuffed tracheal tubes are preferred. PMID- 27277675 TI - ROS homeostasis and metabolism: a dangerous liason in cancer cells. AB - Tumor cells harbor genetic alterations that promote a continuous and elevated production of reactive oxygen species. Whereas such oxidative stress conditions would be harmful to normal cells, they facilitate tumor growth in multiple ways by causing DNA damage and genomic instability, and ultimately, by reprogramming cancer cell metabolism. This review outlines the metabolic-dependent mechanisms that tumors engage in when faced with oxidative stress conditions that are critical for cancer progression by producing redox cofactors. In particular, we describe how the mitochondria has a key role in regulating the interplay between redox homeostasis and metabolism within tumor cells. Last, we will discuss the potential therapeutic use of agents that directly or indirectly block metabolism. PMID- 27277676 TI - Long non-coding RNA regulation of epithelial-mesenchymal transition in cancer metastasis. AB - Metastasis is a multistep process starting with the dissemination of tumor cells from a primary site and ending with secondary tumor development in an anatomically distant location. The epithelial-mesenchymal transition (EMT), a process that endows epithelial tumor cells with mesenchymal properties including reduced adhesion and increased motility, is considered a critical step driving the early phase of cancer metastasis. Although significant progress has been made in understanding the molecular characteristics of EMT, the intracellular mechanisms driving transition through the various stages of EMT remain unclear. In recent years, an increasing number of studies have demonstrated the involvement of long non-coding RNAs (lncRNAs) in tumor metastasis through modulating EMT. LncRNAs and their associated signaling networks have now emerged as new players in the induction and regulation of EMT during metastasis. Here we summarize the recent findings and characterizations of several known lncRNAs involved in the regulation of EMT. We will also discuss the potential use of these lncRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets to slow down or prevent metastatic spread of malignant tumors. PMID- 27277677 TI - KLF4 deletion alters gastric cell lineage and induces MUC2 expression. AB - Gastric cancer is one of the most common types of cancer in the world, particularly in underdeveloped countries. The mechanism of gastric cancer is less understood compared with other types of gastrointestinal (GI) cancers. Kruppel like factor 4 (KLF4) is a zinc-finger transcription factor and is a potential tumor suppressor in GI cancers. In this study, we have generated two mouse models, Rosa-Cre;Klf4(fl/fl) and Lgr5-Cre;Klf4(fl/fl). KLF4 was deleted by Rosa Cre in the gastric epithelia cells or by Lgr5-Cre in the antral stem cells in the adult mice. KLF4 deletion resulted in increased proliferating cells and decreased pit mucous cells. Surprisingly, the intestinal goblet cell marker, MUC2, which is not expressed in normal gastric tissues, was strongly induced at the base of the KLF4-deleted antral glands. To understand the clinical relevance of these findings, we analyzed the expression of KLF4 and MUC2 in human gastric cancer. In a subset of human gastric cancer, the expression of KLF4 is negatively associated with MUC2 expression. In conclusion, KLF4 is essential for normal homeostasis of antral stem cells; loss of KLF4 and expression of MUC2 could be important markers for gastric cancer diagnosis. PMID- 27277678 TI - PAX7 is a required target for microRNA-206-induced differentiation of fusion negative rhabdomyosarcoma. AB - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. RMS can be parsed based on clinical outcome into two subtypes, fusion-positive RMS (FP-RMS) or fusion-negative RMS (FN-RMS) based on the presence or absence of either PAX3-FOXO1 or PAX7-FOXO1 gene fusions. In both RMS subtypes, tumor cells show histology and a gene expression pattern resembling that of developmentally arrested skeletal muscle. Differentiation therapy is an attractive approach to embryonal tumors of childhood including RMS; however, agents to drive RMS differentiation have not entered the clinic and their mechanisms remain unclear. MicroRNA-206 (miR-206) expression increases through normal muscle development and has decreased levels in RMS compared with normal skeletal muscle. Increasing miR 206 expression drives differentiation of RMS, but the target genes responsible for the relief of the development arrest are largely unknown. Using a combinatorial approach with gene and proteomic profiling coupled with genetic rescue, we identified key miR-206 targets responsible for the FN-RMS differentiation blockade, PAX7, PAX3, NOTCH3, and CCND2. Specifically, we determined that PAX7 downregulation is necessary for miR-206-induced cell cycle exit and myogenic differentiation in FN-RMS but not in FP-RMS. Gene knockdown of targets necessary for miR-206-induced differentiation alone or in combination was not sufficient to phenocopy the differentiation phenotype from miR-206, thus illustrating that miR-206 replacement offers the ability to modulate a complex network of genes responsible for the developmental arrest in FN-RMS. Genetic deletion of miR-206 in a mouse model of FN-RMS accelerated and exacerbated tumor development, indicating that both in vitro and in vivo miR-206 acts as a tumor suppressor in FN-RMS at least partially through downregulation of PAX7. Collectively, our results illustrate that miR-206 relieves the differentiation arrest in FN-RMS and suggests that miR-206 replacement could be a potential therapeutic differentiation strategy. PMID- 27277679 TI - DJ-1 deficiency attenuates expansion of liver progenitor cells through modulating the inflammatory and fibrogenic niches. AB - Our previous study suggested that DJ-1 has a critical role in initiating an inflammatory response, but its role in the liver progenitor cell (LPC) expansion, a process highly dependent on the inflammatory niche, remains elusive. The objective of this study is to determine the role of DJ-1 in LPC expansion. The correlation of DJ-1 expression with LPC markers was examined in the liver of patients with hepatitis B or hepatitis C virus (HBV and HCV, respectively) infection, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), nonalcoholic fatty liver disease (NAFLD), cirrhosis or hepatocellular carcinoma (HCC), respectively. The role of DJ-1 in LPC expansion and the formation of LPC associated fibrosis and inflammation was examined in a 3,5-diethoxycarbonyl-1,4 dihydrocollidine (DDC) diet-induced liver injury murine model. We also determined the ability of hepatic stellate cells (HSCs) in recruiting macrophages in DJ-1 knockout (KO) mice. The expression levels of DJ-1 were upregulated in the liver of HBV, HCV, PBC and PSC patients and DDC-fed mice. Additionally, DJ-1 expression was positively correlated with LPC proliferation in patients with liver injury and mice with DDC exposure. DJ-1 has no direct effect on LPC proliferation. Reduced activation of HSCs and collagen deposition were observed in DJ-1 KO mice. Furthermore, infiltrated CD11b(+)Gr-1(low) macrophages and pro-inflammatory factors (IL-6, TNF-alpha) were attenuated in DJ-1 KO mice. Mechanistically, we found that HSCs isolated from DJ-1 KO mice had decreased secretion of macrophage mobilizing chemokines, such as CCL2 and CX3CL1, resulting in impaired macrophage infiltration. DJ-1 positively correlates with LPC expansion during liver injury. DJ-1 deficiency negatively regulates LPC proliferation by impairing the formation of LPC-associated fibrosis and inflammatory niches. PMID- 27277680 TI - Endoplasmic reticulum stress in bone marrow-derived cells prevents acute cardiac inflammation and injury in response to angiotensin II. AB - Inflammation plays an important role in hypertensive cardiac injury. The endoplasmic reticulum (ER) stress pathway is involved in the inflammatory response. However, the role of ER stress in elevated angiotensin II (Ang II) induced cardiac injury remains unclear. In this study, we investigated the role of ER stress in Ang II-induced hypertensive cardiac injury. Transcriptome analysis and quantitative real-time PCR showed that Ang II infusion in mice increased ER stress-related genes expression in the heart. C/EBP homologous protein (CHOP) deficiency, a key mediator of ER stress, increased infiltration of inflammatory cells, especially neutrophils, the production of inflammatory cytokines, chemokines in Ang II-infused mouse hearts. CHOP deficiency increased Ang II-induced cardiac fibrotic injury: (1) Masson trichrome staining showed increased fibrotic areas, (2) immunohistochemistry staining showed increased expression of alpha-smooth muscle actin, transforming growth factor beta1 and (3) quantitative real-time PCR showed increased expression of collagen in CHOP deficient mouse heart. Bone marrow transplantation experiments indicated that CHOP deficiency in bone marrow cells was responsible for Ang II-induced cardiac fibrotic injury. Moreover, TUNEL staining and flow cytometry revealed that CHOP deficiency decreased neutrophil apoptosis in response to Ang II. Taken together, our study demonstrated that hypertension induced ER stress after Ang II infusion. ER stress in bone marrow-derived cells protected acute cardiac inflammation and injury in response to Ang II. PMID- 27277681 TI - ATP2C1 gene mutations in Hailey-Hailey disease and possible roles of SPCA1 isoforms in membrane trafficking. AB - ATP2C1 gene codes for the secretory pathway Ca(2+)/Mn(2+)-ATPase pump type 1 (SPCA1) localizing at the golgi apparatus. Mutations on the human ATP2C1 gene, causing decreased levels of the SPCA1 expression, have been identified as the cause of the Hailey-Hailey disease, a rare skin disorder. In the last few years, several mutations have been described, and here we summarize how they are distributed along the gene and how missense mutations affect protein expression. SPCA1 is expressed in four different isoforms through alternative splicing of the ATP2C1 gene and none of these isoforms is differentially affected by any of these mutations. However, a better understanding of the tissue specific expression of the isoforms, their localization along the secretory pathway, their specific binding partners and the role of the C-terminal tail making isoforms different from each other, will be future goals of the research in this field. PMID- 27277682 TI - Mysm1 is required for interferon regulatory factor expression in maintaining HSC quiescence and thymocyte development. AB - Mysm1(-/-) mice have severely decreased cellularity in hematopoietic organs. We previously revealed that Mysm1 knockout impairs self-renewal and lineage reconstitution of HSCs by abolishing the recruitment of key transcriptional factors to the Gfi-1 locus, an intrinsic regulator of HSC function. The present study further defines a large LSKs in >8-week-old Mysm1(-/-) mice that exhibit increased proliferation and reduced cell lineage differentiation compared with those of WT LSKs. We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at lower levels in Mysm1(-/-) HSCs, and Mysm1 enhanced function of the IRF2 and IRF8 promoters, suggesting that Mysm1 governs the IRFs for HSC homeostasis. We further found that the lower expressions of IRF2 and IRF8 led to an enhanced transcription of p53 in Mysm1(-/-) HSCs, which was recently defined to have an important role in mediating Mysm1(-/-)-associated defects. The study also revealed that Mysm1(-/-) thymocytes exhibited lower IRF2 expression, but had higher Sca1 expression, which has a role in mediating thymocyte death. Furthermore, we found that the thymocytes from B16 melanoma-bearing mice, which display severe thymus atrophy at late tumor stages, exhibited reduced Mysm1 and IRF2 expression but enhanced Sca1 expression, suggesting that tumors may downregulate Mysm1 and IRF2 for thymic T-cell elimination. PMID- 27277683 TI - MicroRNA-155 facilitates skeletal muscle regeneration by balancing pro- and anti inflammatory macrophages. AB - Skeletal muscle has remarkable regeneration capacity and regenerates in response to injury. Muscle regeneration largely relies on muscle stem cells called satellite cells. Satellite cells normally remain quiescent, but in response to injury or exercise they become activated and proliferate, migrate, differentiate, and fuse to form multinucleate myofibers. Interestingly, the inflammatory process following injury and the activation of the myogenic program are highly coordinated, with myeloid cells having a central role in modulating satellite cell activation and regeneration. Here, we show that genetic deletion of microRNA 155 (miR-155) in mice substantially delays muscle regeneration. Surprisingly, miR 155 does not appear to directly regulate the proliferation or differentiation of satellite cells. Instead, miR-155 is highly expressed in myeloid cells, is essential for appropriate activation of myeloid cells, and regulates the balance between pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages during skeletal muscle regeneration. Mechanistically, we found that miR-155 suppresses SOCS1, a negative regulator of the JAK-STAT signaling pathway, during the initial inflammatory response upon muscle injury. Our findings thus reveal a novel role of miR-155 in regulating initial immune responses during muscle regeneration and provide a novel miRNA target for improving muscle regeneration in degenerative muscle diseases. PMID- 27277698 TI - The role of alpha1-adrenergic receptors in regulating metabolism: increased glucose tolerance, leptin secretion and lipid oxidation. AB - The role of alpha1-adrenergic receptors (alpha1-ARs) and their subtypes in metabolism is not well known. Most previous studies were performed before the advent of transgenic mouse models and utilized transformed cell lines and poorly selective antagonists. We have now studied the metabolic regulation of the alpha1A- and alpha1B-AR subtypes in vivo using knock-out (KO) and transgenic mice that express a constitutively active mutant (CAM) form of the receptor, assessing subtype-selective functions. CAM mice increased glucose tolerance while KO mice display impaired glucose tolerance. CAM mice increased while KO decreased glucose uptake into white fat tissue and skeletal muscle with the CAM alpha1A-AR showing selective glucose uptake into the heart. Using indirect calorimetry, both CAM mice demonstrated increased whole body fatty acid oxidation, while KO mice preferentially oxidized carbohydrate. CAM alpha1A-AR mice displayed significantly decreased fasting plasma triglycerides and glucose levels while alpha1A-AR KO displayed increased levels of triglycerides and glucose. Both CAM mice displayed increased plasma levels of leptin while KO mice decreased leptin levels. Most metabolic effects were more efficacious with the alpha1A-AR subtype. Our results suggest that stimulation of alpha1-ARs results in a favorable metabolic profile of increased glucose tolerance, cardiac glucose uptake, leptin secretion and increased whole body lipid metabolism that may contribute to its previously recognized cardioprotective and neuroprotective benefits. PMID- 27277684 TI - Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis. AB - BC200 is a long non-coding RNA (lncRNA) that has been implicated in the regulation of protein synthesis, yet whether dysregulation of BC200 contributes to the pathogenesis of human diseases remains elusive. In this study, we show that BC200 is upregulated in breast cancer; among breast tumor specimens there is a higher level of BC200 in estrogen receptor (ER) positive than in ER-negative tumors. Further experiments show that activation of estrogen signaling induces expression of BC200. To determine the significance of ER-regulated BC200 expression, we knockout (KO) BC200 by CRISPR/Cas9. BC200 KO suppresses tumor cell growth in vitro and in vivo by expression of the pro-apoptotic Bcl-xS isoform. Mechanistically, BC200 contains a 17-nucleotide sequence complementary to Bcl-x pre-mRNA, which may facilitate its binding to Bcl-x pre-mRNA and recruitment of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, a known splicing factor. Consequently, hnRNP A2/B1 interferes with association of Bcl-x pre-mRNA with the Bcl-xS-promoting factor Sam68, leading to a blockade of Bcl-xS expression. Together, these results suggest that BC200 plays an oncogenic role in breast cancer. Thus, BC200 may serve as a prognostic marker and possible target for attenuating deregulated cell proliferation in estrogen-dependent breast cancer. PMID- 27277699 TI - Occupational injuries and sick leaves in household moving works. AB - BACKGROUND: This study is concerned with household moving works and the characteristics of occupational injuries and sick leaves in each step of the moving process. METHODS: Accident data for 392 occupational accidents were categorized by the moving processes in which the accidents occurred, and possible incidents and sick leaves were assessed for each moving process and hazard factor. RESULTS: Accidents occurring during specific moving processes showed different characteristics depending on the type of accident and agency of accidents. The most critical form in the level of risk management was falls from a height in the 'lifting by ladder truck' process. Incidents ranked as a 'High' level of risk management were in the forms of slips, being struck by objects and musculoskeletal disorders in the 'manual materials handling' process. Also, falls in 'loading/unloading', being struck by objects during 'lifting by ladder truck' and driving accidents in the process of 'transport' were ranked 'High'. CONCLUSION: The findings of this study can be used to develop more effective accident prevention policy reflecting different circumstances and conditions to reduce occupational accidents in household moving works. PMID- 27277700 TI - [Hypothermic treatment in deceased organ donors and function of donor kidneys]. PMID- 27277701 TI - Persistence of antibiotic resistance and plasmid-associated genes in soil following application of sewage sludge and abundance on vegetables at harvest. AB - Sewage sludge recovered from wastewater treatment plants contains antibiotic residues and is rich in antibiotic resistance genes, selected for and enriched in the digestive tracts of human using antibiotics. The use of sewage sludge as a crop fertilizer constitutes a potential route of human exposure to antibiotic resistance genes through consumption of contaminated crops. Several gene targets associated with antibiotic resistance (catA1, catB3, ereA, ereB, erm(B), str(A), str(B), qnrD, sul1, and mphA), mobile genetic elements (int1, mobA, IncW repA, IncP1 groups -alpha, -beta, -delta, -gamma, -epsilon), and bacterial 16S rRNA (rrnS) were quantified by qPCR from soil and vegetable samples obtained from unamended and sludge-amended plots at an experimental field in London, Ontario. The qPCR data reveals an increase in abundance of gene targets in the soil and vegetables samples, indicating that there is potential for additional crop exposure to antibiotic resistance genes carried within sewage sludge following field application. It is therefore advisable to allow an appropriate delay period before harvesting of vegetables for human consumption. PMID- 27277702 TI - Proposal for probing energy transfer pathway by single-molecule pump-dump experiment. AB - The structure of Fenna-Matthews-Olson (FMO) light-harvesting complex had long been recognized as containing seven bacteriochlorophyll (BChl) molecules. Recently, an additional BChl molecule was discovered in the crystal structure of the FMO complex, which may serve as a link between baseplate and the remaining seven molecules. Here, we investigate excitation energy transfer (EET) process by simulating single-molecule pump-dump experiment in the eight-molecules complex. We adopt the coherent modified Redfield theory and non-Markovian quantum jump method to simulate EET dynamics. This scheme provides a practical approach of detecting the realistic EET pathway in BChl complexes with currently available experimental technology. And it may assist optimizing design of artificial light harvesting devices. PMID- 27277703 TI - Graphene oxide-based electrochemical label-free detection of glycoproteins down to aM level using a lectin biosensor. AB - A label-free ultrasensitive impedimetric biosensor with lectin immobilised on graphene oxide (GO) for the detection of glycoproteins from 1 aM is shown here. This is the first time a functional lectin biosensor with lectin directly immobilised on a graphene-based interface without any polymer modifier has been described. The study also shows that hydrophilic oxidative debris present on GO has a beneficial effect on the sensitivity of (8.46 +/- 0.20)% per decade for the lectin biosensor compared to the sensitivity of (4.52 +/- 0.23)% per decade for the lectin biosensor built up from GO with the oxidative debris washed out. PMID- 27277704 TI - Adenovirus with p16 gene exerts antitumor effect on laryngeal carcinoma Hep2 cells. AB - Laryngeal cancer is an uncommon form of cancer. The tumor suppressor P16, known to be mutated or deleted in various types of human tumor, including laryngeal carcinoma, is involved in the formation and development of laryngeal carcinoma. It has been previously reported that the inactivation or loss of P16 is associated with the acquisition of malignant characteristics. The current study hypothesized that restoring wild-type P16 activity into P16-null malignant Hep2 cells may exert an antitumor effect. A recombinant adenovirus carrying the P16 gene (Ad-P16) was used to infect and express high levels of P16 protein in P16 null Hep2 cells. Cell proliferation and invasion assays and polymerase chain reaction were performed to evaluate the effects of the P16 gene on cell proliferation and the antitumor effect on Hep2 cells. The results demonstrated that the Hep2 cells infected with Ad-P16 exhibited significantly reduced cell proliferation, invasion and tumor volume compared with untreated or control adenovirus cells. Furthermore, the expression of laryngeal carcinoma-associated genes, EGFR, survivin and cyclin D1, were measured in Ad-P16-infected cells and were significantly reduced compared with control groups. The results of the current study demonstrate that restoring wild-type P16 activity into P16-null Hep2 cells exerts an antitumor effect. PMID- 27277705 TI - Survey of US Patients with Multiple Sclerosis: Comparison of the New Electronic Interferon Beta-1b Autoinjector (BETACONNECTTM) With Mechanical Autoinjectors. AB - INTRODUCTION: Patients with multiple sclerosis (MS) generally undergo long-term treatment with disease-modifying therapies (DMTs). In the US, patients taking glatiramer acetate, interferon beta-1a, or interferon beta-1b, typically use a mechanical autoinjector. Recent survey results have shown that using an electronic autoinjector, such as BETACONNECTTM (Bayer Pharma AG) for interferon beta-1b/Betaseron(r) (Bayer Pharma AG) may reduce injection discomfort and increase patient satisfaction with treatment. The aim of the current survey was to assess patient perceptions of BETACONNECT compared with mechanical autoinjectors using a survey integrated with demonstrations and simulated injections with BETACONNECT. METHODS: Patients with MS currently using mechanical autoinjectors for glatiramer acetate/Copaxone(r) (Teva Pharmaceuticals USA, Inc.), interferon beta-1a/Rebif(r) (EMD Serono Inc.), or interferon beta 1b/Extavia(r) (Novartis Pharmaceuticals Corp.), participated in a 60-min in person interview. Patients rated the importance of 18 ideal autoinjector attributes, and the performance of their current autoinjectors across these attributes. BETACONNECT was demonstrated and patients performed simulated injections with BETACONNECT before rating it across the same attributes. Patient overall autoinjector preference was assessed. RESULTS: Ninety patients completed the survey: 63 were using autoinjectors for Copaxone, 25 for Rebif, and 2 for Extavia. BETACONNECT scored higher than mechanical autoinjectors across all 18 attributes. The top attributes of an ideal autoinjector were the injection process is easy overall, easy to push the button to start the injection, and autoinjector is comfortable to hold during injections. Unique BETACONNECT features most valued by patients were the built-in dwell time, self-check function, greater ability to customize injections, adjustment of injection speed, low injection noise, and automatic needle retraction. Overall, 75 out of 90 patients (83%) expressed a preference for BETACONNECT over their current autoinjector. CONCLUSION: BETACONNECT attributes and features were highly rated by patients, compared with both an ideal autoinjector and their current mechanical autoinjectors. These findings suggest that the use of BETACONNECT may increase patient satisfaction and potentially increase overall medication adherence. FUNDING: Bayer HealthCare Pharmaceuticals. PMID- 27277706 TI - Microcirculatory blood flow during cardiac arrest and cardiopulmonary resuscitation does not correlate with global hemodynamics: an experimental study. AB - BACKGROUND: Current research highlights the role of microcirculatory disorders in post-cardiac arrest patients. Affected microcirculation shows not only dissociation from systemic hemodynamics but also strong connection to outcome of these patients. However, only few studies evaluated microcirculation directly during cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of our experimental study in a porcine model was to describe sublingual microcirculatory changes during CA and CPR using recent videomicroscopic technology and provide a comparison to parameters of global hemodynamics. METHODS: Cardiac arrest was induced in 18 female pigs (50 +/- 3 kg). After 3 min without treatment, 5 min of mechanical CPR followed. Continuous hemodynamic monitoring including systemic blood pressure and carotid blood flow was performed and blood lactate was measured at the end of baseline and CPR. Sublingual microcirculation was assessed by the Sidestream Dark Field (SDF) technology during baseline, CA and CPR. Following microcirculatory parameters were assessed off-line separately for capillaries (<=20 um) and other vessels: total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). RESULTS: In comparison to baseline the CA small vessel microcirculation was only partially preserved: TVD 15.64 (13.59-18.48) significantly decreased to 12.51 (10.57-13.98) mm/mm(2), PVD 15.57 (13.56-17.80) to 5.53 (4.17-6.60) mm/mm(2), PPV 99.64 (98.05 100.00) to 38.97 (27.60-46.29) %, MFI 3.00 (3.00-3.08) to 1.29 (1.08-1.58) and HI increased from 0.08 (0.00-0.23) to 1.5 (0.71-2.00), p = 0.0003 for TVD and <0.0001 for others, respectively. Microcirculation during ongoing CPR in small vessels reached 59-85 % of the baseline values: TVD 13.33 (12.11-15.11) mm/mm(2), PVD 9.34 (7.34-11.52) mm/mm(2), PPV 72.34 (54.31-87.87) %, MFI 2.04 (1.58-2.42), HI 0.65 (0.41-1.07). The correlation between microcirculation and global hemodynamic parameters as well as to lactate was only weak to moderate (i.e. Spearman's rho 0.02-0.51) and after adjustment for multiple correlations it was non-significant. CONCLUSIONS: Sublingual microcirculatory parameters did not correlate with global hemodynamic parameters during simulated porcine model of CA and CPR. SDF imaging provides additional information about tissue perfusion in the course of CPR. PMID- 27277707 TI - Ecology of urban malaria vectors in Niamey, Republic of Niger. AB - BACKGROUND: Urbanization in African cities has major impact on malaria risk. Niamey, the capital of the Republic of Niger, is situated in the West African Sahel zone. The short rainy season and human activities linked with the Niger River influence mosquito abundance. This study aimed at deciphering the factors of distribution of urban malaria vectors in Niamey. METHODS: The distribution of mosquito aquatic stages was investigated monthly from December 2002 to November 2003, at up to 84 breeding sites, throughout Niamey. An exploratory analysis of association between mosquito abundance and environmental factors was performed by a Principal Component Analysis and confirmed by Kruskall-Wallis non-parametric test. To assess the relative importance of significant factors, models were built for Anopheles and Culicinae. In a second capture session, adult mosquitoes were collected weekly with pyrethrum sprays and CDC light-traps from June 2008 to June 2009 in two differentiated urban areas chosen after the study's first step. Members of the Anopheles gambiae complex were genotyped and Anopheles females were tested for the presence of Plasmodium falciparum circumsporozoite antigens using ELISA. RESULTS: In 2003, 29 % of 8420 mosquitoes collected as aquatic stages were Anopheles. They were significantly more likely to be found upstream, relatively close to the river and highly productive in ponds. These factors remained significant in regression and generalized linear models. The Culicinae were found significantly more likely close to the river, and in the main temporary affluent stream. In 2009, Anopheles specimens, including Anopheles gambiae s.l. (95 %), but also Anopheles funestus (0.6 %) accounted for 18 % of the adult mosquito fauna, with a large difference between the two sampled zones. Three members of the An. gambiae complex were found: Anopheles arabiensis, Anopheles coluzzii, and An. gambiae. Nineteen (1.3 %) out of 1467 females tested for P. falciparum antigen were found positive. CONCLUSION: The study provides valuable update knowledge on malaria vector ecology and distribution in Niamey. The identification of spatial and environmental risk factors could pave the way to larval source management strategy and allow malaria vector control to focus on key zones for the benefit of the community. PMID- 27277708 TI - Akreos Adapt AO Intraocular lens opacification after vitrectomy in a diabetic patient: a case report and review of the literature. AB - BACKGROUND: Postoperative optic opacification of hydrophilic acrylic intraocular lenses (IOLs) is an uncommon complication leading to IOL explantation. In the past decade, several studies reported that the granular deposits responsible for the opacification were probably calcium and phosphate salts; however, the exact mechanism causing calcification of IOLs is unknown. The aim of this study is to describe clinical and laboratory findings of a case of late postoperative opacification of an aspheric hydrophilic acrylic IOL (Akreos Adapt AO) after vitrectomy. CASE PRESENTATION: A 60-year-old woman diagnosed with cataract and severe nonproliferative diabetic retinopathy (NPDR) underwent uneventful phacoemulsification and hydrophilic acrylic IOL (Akreos Adapt AO, Bausch & Lomb) implantation in both eyes. Seven months later, the woman came back with a complaint of blurry vision in the left eye. Fundus examination revealed vitreous hemorrhage in the left eye veiling the retinal detail. A 23-gauge vitrectomy with endolaser treatment was performed in the left eye. Ten months after the vitrectomy, the patient complained of decreased visual acuity in the left eye again. On slit-lamp examination, we observed a well circumscribed centrally and paracentrally located opacification within the pupillary area localized to the anterior surface of the IOL. The IOL was explanted from the left eye together with the capsular bag, and an iris-claw lens (Artisan Aphakia OPHTEC) was implanted. The explanted IOL was examined under pathological evaluation (alizarin red method). CONCLUSIONS: IOL opacification is a rare event. We described a case of postoperative opacification of the Akreos Adapt AO IOL after vitrectomy in a patient with proliferative diabetic retinopathy and found the deposits on the anterior surface of the IOL consisted of calcium aggregates. Given the higher frequency of postoperative opacification observed in diabetic patients, hydrophilic acrylic IOLs should be used with caution in patients with diabetes. PMID- 27277709 TI - Primary Care Provider Views About Usefulness and Dissemination of a Web-Based Depression Treatment Information Decision Aid. AB - BACKGROUND: Decisions related to mental health are often complex, problems often remain undetected and untreated, information unavailable or not used, and treatment decisions frequently not informed by best practice or patient preferences. OBJECTIVE: The objective of this paper was to obtain the opinions of health professionals working in primary health care settings about a Web-based information decision aid (IDA) for patients concerning treatment options for depression and the dissemination of the resources in primary care settings. METHODS: Participants were recruited from primary care clinics in Winnipeg and Ottawa, Canada, and included 48 family physicians, nurses, and primary care staff. The study design was a qualitative framework analytic approach of 5 focus groups. Focus groups were conducted during regular staff meetings, were digitally recorded, and transcripts created. Analysis involved a content and theme analysis. RESULTS: Seven key themes emerged including the key role of the primary care provider, common questions about treatments, treatment barriers, sources of patient information, concern about quality and quantity of available information, positive opinions about the IDA, and disseminating the IDA. The most common questions mentioned were about medication and side effects and alternatives to medication. Patients have limited access to alternative treatment options owing to cost and availability. CONCLUSIONS: Practitioners evaluated the IDA positively. The resources were described as useful, supportive of providers' messages, and accessible for patients. There was unanimous consensus that information needs to be available electronically through the Internet. PMID- 27277711 TI - Assignment of an impact factor to our journal. PMID- 27277710 TI - Cardiovascular implanted electronic devices in people towards the end of life, during cardiopulmonary resuscitation and after death: guidance from the Resuscitation Council (UK), British Cardiovascular Society and National Council for Palliative Care. AB - The Resuscitation Council (UK), the British Cardiovascular Society (including the British Heart Rhythm Society and the British Society for Heart Failure) and the National Council for Palliative Care recognise the importance of providing clear and consistent guidance on management of cardiovascular implanted electronic devices (CIEDs) towards the end of life, during cardiorespiratory arrest and after death. This document has been developed to provide guidance for the full range of healthcare professionals who may encounter people with CIEDs in the situations described and for healthcare managers and commissioners. The authors recognise that some patients and people close to patients may also wish to refer to this document. It is intended as an initial step to help to ensure that people who have CIEDs, or are considering implantation of one, receive explanation of and understand the practical implications and decisions that this entails; to promote a good standard of care and service provision for people in the UK with CIEDs in the circumstances described; to offer relevant ethical and legal guidance on this topic; to offer guidance on the delivery of services in relation to deactivation of CIEDs where appropriate; to offer guidance on whether any special measures are needed when a person with a CIED receives cardiopulmonary resuscitation; and to offer guidance on the actions needed when a person with a CIED dies. PMID- 27277712 TI - Practical considerations for a method of rapid cardiac function analysis based on three-dimensional speckle tracking in a three-dimensional diagnostic ultrasound system. AB - PURPOSE: The purpose of this study was to validate the accuracy of our novel 3D speckle tracking method by using numerical data, and to demonstrate the rapid processing of this method by using data obtained from human subjects. METHODS: In order to create a method that can rapidly assess cardiac function in regional heart wall segments, a 3D speckle tracking algorithm was created that focuses on data quality and performance. Prototype application software based on this algorithm was written to evaluate cardiac wall motion and to calculate indices such as strain. Time series 3D image data were generated for artificial numerical models that simulate the shape of the left ventricle and exhibit various types of motion. We compared observed values returned by the algorithm with expected values yielded by the models. This software was also applied to volume data of the human heart acquired by a 3D ultrasound system. RESULTS: Measurement of the indices was evaluated by using an error ratio that was a residual between an expected value and estimated one divided by the expected value. The average error ratio of the time series volumes was less than 5% for all indices, and no individual error ratio was more than 10% for numerical models. The process was complete within 0.5 s per frame for human heart volumes. CONCLUSION: This application software can provide good estimates of various wall motion indices. The results are similar to data from numerical models, and are provided quickly enough for routine clinical usage. PMID- 27277713 TI - Comparison of ultrasound colored image views produced by application of statistical analysis of radio-frequency signals and histological findings in patients with chronic hepatitis C. AB - PURPOSE: To assess the tissue characteristics of chronic liver disease, we statistically analyzed the speckle signal from liver parenchyma. SUBJECTS AND METHODS: Analysis was performed for 65 patients with biopsy-proven chronic hepatitis C; individuals with fatty liver, heavy drinkers, and those with a thick abdominal wall were excluded. The probability density function of radio-frequency signal amplitude was statistically analyzed using a new analytical method. We focused on strong signals which deviated remarkably from the Rayleigh distribution. By applying the analytical results, lesions that caused the strong signals were displayed as red scatter overlaid on B-mode images (we called the red scatter "US-Red" in this study). US-Red% occupancy on the color image was statistically compared with pathological findings. RESULTS: US-Red suggests the existence of an acoustic reflectional plane mainly formed of fibrous bridge and septa. US-Red% increased significantly with progression of liver fibrosis stage. US-Red% varied widely in cirrhosis, and US-Red% in the large nodule group was significantly higher than that in the small nodule group. CONCLUSION: The results suggest that US-Red% is useful for evaluating liver fibrosis stage (F1-3) and the size of nodules in cirrhosis. In addition, visually detecting the acoustic reflectional plane, which increases with progression of disease, as color images will be clinically beneficial. PMID- 27277714 TI - Sonographic finding of papillary thyroid carcinoma with nodular fasciitis-like stroma. AB - Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is an extremely rare variant of papillary thyroid carcinoma characterized by prominent stromal cell proliferation. To our knowledge, sonographic findings of PTS-NFS have not been reported. Here, we report a case of PTC-NFS that presented as a homogenous and hypoechoic mass in the peripheral portion of the left thyroid gland on sonography in a 35-year-old pregnant woman. PMID- 27277715 TI - Retroperitoneal abscess cured by percutaneous drainage with ultrasonography. AB - This report presents an unusual case of an extensive retroperitoneal abscess caused by appendicitis in a child. A 3-year-old boy who presented with right lower abdominal pain and a high fever was found, by abdominal ultrasonography (US) and computed tomography (CT), to have a retroperitoneal abscess. Percutaneous drainage of the abscess under US guidance was successfully performed. There was no sign of recurrence of appendicitis or the abscess 12 months after the drainage. PMID- 27277716 TI - Three cases of angiomyolipoma: diagnostic imaging by contrast-enhanced ultrasonography. AB - We used contrast-enhanced ultrasound using the Sonazoid microbubble contrast agent to diagnose three cases of hepatic angiomyolipoma, which is a rare benign tumor. Some characteristic findings are obtained in the early vascular phase, for example fork-like tumor vessels. However, a variety of findings are seen after the early vascular phase because of microbubbles circulating the vascular enriched tumor. PMID- 27277717 TI - Pseudoaneurysm in a chronic pancreatitis patient: report of a case, with emphasis on contrast-enhanced sonograms. AB - The association between pseudoaneurysm of the splenic artery and pancreatitis is now established. Rupture of an aneurysm is a lethal condition, and early diagnosis and treatment are required to prevent this hazardous life-threatening complication. In our case, early detection of pseudoaneurysm of the splenic artery enabled us to start prompt embolization, which yielded good results. Splenic infarction is known to be an important and frequent complication of transarterial embolization of splenic artery aneurysms. Thus, when performing transarterial embolization of a splenic artery aneurysm, this complication must be kept in mind and it is absolutely necessary to confirm the presence or absence of this complication after embolization of the aneurysm. In our case of pseudoaneurysm of the splenic artery due to acute aggravation of chronic pancreatitis, contrast-enhanced ultrasonography confirmed the spleen to be free from infarction. Thus, this technique is strongly recommended in such instances. PMID- 27277718 TI - Parametric imaging using contrast-enhanced ultrasound with Sonazoid for hepatocellular carcinoma. AB - PURPOSE: To clarify the usefulness of parametric imaging using contrast-enhanced ultrasound (CE-US) with Sonazoid by comparing parametric images of hepatocellular carcinoma (HCC) with histopathological findings. METHODS: Two patients with HCCs underwent CE-US with Sonazoid before surgical resection. A single focus point was set at the lower margin of the tumor, and a bolus intravenous injection of Sonazoid (0.5 ml) was administered. Images of the ideal scanning plane were displayed in real-time mode for the early vascular phase. We analyzed these images using prototype PC software. The software watches, pixel by pixel, the increase in the intensity due to the inflow of the microbubbles, and displays colors if the intensity becomes larger than a certain threshold. Parametric images were compared with histopathological findings. RESULTS: The level of blood flow in the tumor could be visually evaluated using a single image by expressing the detailed hemodynamics of the tumor in terms of differences in color using a time axis appropriate for each case. CONCLUSIONS: Parametric imaging is a very useful way of facilitating straightforward visualization of the level of blood flow within HCC and the distribution of histopathological findings in single static images. PMID- 27277719 TI - A case of high-flow hepatic hemangioma: analysis by parametoric imaging using sonazoid-enhanced ultrasonography. PMID- 27277720 TI - Ductal adenoma of the breast. PMID- 27277723 TI - Hybrid or integrated? An imagined view of medical imaging in the future. PMID- 27277721 TI - Social disparities in parental smoking and young children's exposure to secondhand smoke at home: a time-trend analysis of repeated cross-sectional data from the German KiGGS study between 2003-2006 and 2009-2012. AB - BACKGROUND: Children who are exposed to secondhand smoke (SHS) have an increased risk of a wide range of health problems and illnesses. Smoke-free legislation aims to improve indoor air quality and in this way protect the health of people who do not smoke. This paper examines trends in SHS exposure at home among children in Germany since the introduction of smoking bans in public places. Special focus is placed on the importance of the family of origin's socioeconomic status (SES) and on parental smoking behaviour. METHODS: The analyses are based on two waves of the "German Health Interview and Examination Survey for Children and Adolescents" (KiGGS)-one of which was conducted immediately before the introduction of central smoke-free legislation in the 2003-2006 period, the other approximately 6 years later from 2009 to 2012. A comparison is made between the answers given by the parents of children aged between 0 to 6 (KiGGS baseline study, n = 6680; KiGGS Wave 1, n = 4455). Domestic SHS exposure is covered in the parent interviews by asking whether anyone is allowed to smoke at home in the presence of their child. Parental smoking behaviour is determined separately for mothers and fathers. SES is determined on the basis of the parents' education, occupational status and income. RESULTS: The percentage of 0- to 6-year-old children exposed to SHS in the parental home fell from 23.9 to 6.6 % in the period from 2003-2006 to 2009-2012. At the same time, the percentage of children with at least one parent who smokes decreased from 49.8 to 41.8 %. While relative social inequalities in parental smoking behaviour have tended to increase over time, inequalities in domestic SHS exposure have persisted. Children whose parents smoke and children from low-SES families are still most likely to be exposed to tobacco smoke. In both study periods and after statistical adjustment for parental smoking behaviour, children with a low SES had a 6.6-fold higher risk for SHS exposure in the parental home than children from high-SES households. CONCLUSIONS: The results of the KiGGS study show that the proportion of children in Germany who are exposed to SHS at home has declined significantly over the last few years. There is much to suggest that the smoke-free legislation that has been introduced in Germany has led to a heightened awareness of the health risks of SHS both in public and in the private sphere, as well as to a denormalization of smoking. Children whose parents smoke, and among them particularly children from socially disadvantaged families, should be recognised as key target groups when implementing future tobacco-control measures. PMID- 27277722 TI - Grifolin induces autophagic cell death by inhibiting the Akt/mTOR/S6K pathway in human ovarian cancer cells. AB - Grifolin, a secondary metabolic product isolated from the mushroom Albatrellus confluence, has been reported to possess antitumor activities in various tumors. To date, no report exists on the role of autophagy in grifolin-treated human ovarian cancer cells. In the present study, we investigated the effect and the mechanism of autophagy in ovarian cancer. Ovarian cancer cell lines A2780 and SKOV3 were treated with grifolin. Cell proliferation was assessed by MTT assay and the autophagic effect was determined using flow cytometry, electron microscopy, immunofluorescence staining and GFP-LC3 puncta formation assay. The expression of autophagy markers and the main autophagy-associated Akt/mTOR/S6K pathway proteins were measured by western blot analysis. MTT assay indicated that grifolin inhibits the proliferation of human ovarian cancer cell lines A2780 and SKOV3. Flow cytometry, electron microscopy, immunofluorescence and GFP-LC3 puncta formation assay proved that grifolin induces autophagic cell death in human ovarian cancer. The results of the western blot analysis suggested that grifolin treatment leads to upregulation of autophagy markers LC3B, Atg7, Beclin-1 along with downregulation of P62. In addition, the proteins of the pathways p-Akt, p mTOR, p-p70S6K and p-4E-BP1 were downregulated while the total of these proteins remained unaffected. The present study indicated that grifolin could induce autophagic cell death in human ovarian cancer by inhibiting the Akt/mTOR/S6K pathway. PMID- 27277724 TI - Development of an ultra-broadband ultrasonic imaging system: prototype mechanical sector device. AB - PURPOSE: We constructed an ultra-broadband ultrasonic transducer in a mechanical sector device, and prototyped a system to generate real-time images with higher harmonics. The potential of the system to reduce speckle was also studied. METHODS: To efficiently detect the higher harmonic components in echo signals, in addition to the transmitting transducer, another transducer only for broadband reception is necessary. We constructed a receiving transducer by bonding a polyvinylidene fluoride (PVDF) high-polymer piezofilm to the radiation surface of the transmitting lead zirconate titanate (PZT) transducer. By building this PZT PVDF bi-layered ultrasonic probe into a mechanical sector scanner of an ultrasonic diagnosis system, an ultra-broadband ultrasonic imaging system capable of real-time imaging was prototyped. RESULTS: Using images of phantoms in water acquired using the prototype system, the acquisition of higher harmonic images with less noise up to the fourth order was demonstrated. In addition, we confirmed that the logarithmic summation of harmonic components from the fundamental to the fourth harmonic effectively reduces speckle noise in the images. CONCLUSIONS: By obtaining an echo signal from phantoms using a PZT-PVDF bi-layered ultrasonic mechanical sector probe, real-time imaging was carried out, and the effectiveness of its higher harmonic components from the fundamental to the fourth harmonic was confirmed with respect to speckle reduction. PMID- 27277725 TI - A fundamental study for quantitative measurement of ultrasound contrast concentration by low mechanical index contrast ultrasonography. AB - PURPOSE: In high mechanical index (MI) contrast ultrasonography it has been shown that the power of contrast signal intensity (CI) has a strong linear correlation with the concentration of the ultrasound contrast agent under conditions of constant applied acoustic pressure. However, it is unclear whether the linearity is preserved in low-MI contrast ultrasonography. Thus, we investigated the relationship between ultrasound contrast concentration and CI in vitro. METHODS: Solutions of the ultrasound contrast agents Definity and Imagent were prepared at concentrations of 0.5, 2, 8, 32, and 128 MUl/l. Placing a jelly block between the transducer and the solution, the solutions were transmitted using pulse subtraction imaging with an MI of 0.05, 0.1, and 0.5. CI was measured in dB in a region of interest 3 mm in height placed just below the border between the jelly and the solution. Data were plotted using double logarithm scales, where the concentration was expressed in dB as 10 * log (concentration). RESULTS: CI in dB had a strong linear correlation with concentration in dB for both agents with any MI. Best fitted slopes were close to 1, indicating that the power of CI is proportional to the concentration. CONCLUSIONS: In low-MI contrast ultrasonography, the power of CI is proportional to contrast concentration, and CI in dB is logarithmic to the concentration. Thus, the microbubble concentration can be quantitatively measured even in low-MI contrast ultrasonography. PMID- 27277726 TI - Analysis of posterior echoes using reconstructed vertical ultrasound images. AB - PURPOSE: To evaluate the role of vertical images reconstructed using 3-D data in the analysis of posterior echoes. METHODS: Reconstructed vertical images of US phantoms with the following artifacts were retrieved and analyzed: acoustic shadowing (clean and dirty); posterior echo enhancement (with/without lateral shadowing); and reverberation artifacts (clean and dirty). RESULTS: For acoustic shadowing, a stone and posterior clean acoustic shadowing were imaged as an echogenic mass or an echogenic ring containing a central echo-free area. However, the stone and dirty acoustic shadowing were imaged as an echogenic mass or an echogenic mass consisting of many fine echo spots disseminated throughout the whole mass. For posterior echo enhancement, when lateral shadowing is present, the cyst and posterior echo enhancement are imaged as a round anechoic mass or a triple circle consisting of a thin anechoic outer rim, an echogenic ring, and an anechoic center. However, when lateral shadowing is absent, they are imaged as a round anechoic mass or a double circle consisting of an echogenic outer rim and an anechoic center. For clean reverberation artifacts and dirty reverberation artifacts, vertical images of clean reverberation artifacts consist of either a homogeneous echogenic area or an absent signal. However, vertical images of dirty reverberation artifacts consist of a homogeneous echogenic area and an area consisting of fine echo spots. CONCLUSION: Our study suggests that reconstructed, previously unattainable, vertical plane images help us better understand the mode of posterior echoes. PMID- 27277727 TI - Measurement of renal blood flow in human subjects using the ultrasound velocity profiling technique. AB - PURPOSE: To (1) assess the accuracy of the ultrasound velocity profiling (USVP) technique of renal blood flow (RBF) measurement in normal subjects and (2) compare renal blood flow measurements obtained using USVP and renal clearance rate in patients with renal diseases. METHODS: First, we calculated unilateral renal blood flow (unil-RBF) using USVP and the clearance rate of para aminohippuric acid (CPAH) simultaneously in six healthy male subjects. We then compared unil-RBFUSVP and unil-RBFPAH in nine patients with chronic glomerulonephritis (CGN). RESULTS: In the first study, the limits of agreement in a Bland-Altman plot ranged from -325.3 to 32.0 ml/min per 1.48 m(2). The mean bias was -146.7 ml/min per 1.48 m(2). Subdivision for values of unil-RBFUSVP by flow showed small discrepancies in values above 280 ml/min per 1.48 m(2): mean bias, -98.2 ml/min per 1.48 m(2); limits of agreement, -223.3 to 26.8 ml/min per 1.48 m(2). The three patients in the second study had immunoglobulin A (IgA) nephropathy, in whom unil-RBFPAH was estimated as being markedly lower than unil RBFUSVP, contrary to the primary result. CONCLUSION: Despite its consistent negative bias, USVP may be a reliable method of quantifying renal blood flow noninvasively when measured values exceed 280 ml/min per 1.48 m(2). We assumed that the p-aminohippurate extraction rate (EPAH) was profoundly impaired in the three patients with IgA nephropathy. PMID- 27277728 TI - Management of transvaginal ultrasound-guided absolute ethanol sclerotherapy for ovarian endometriotic cysts. AB - PURPOSE: Endometriosis and endometriotic ovarian cysts are common gynecologic diseases. Excision of the cyst wall by laparotomy or laparoscopy is the standard treatment for endometriotic ovarian cysts. However, some young patients with cysts would prefer not to have an abdominal incision. We reviewed and assessed the effectiveness of transvaginal ultrasound-guided ethanol sclerotherapy in these patients. METHODS: Eighteen patients with endometriotic ovarian cysts underwent transvaginal ultrasound-guided aspiration and ethanol sclerotherapy using spinal anesthesia. The contents of the cysts were drained and sent for cytological examination. The cyst cavities were washed with absolute ethanol, and the cysts were then filled with absolute ethanol for 5 min. The patients were followed up with transvaginal ultrasonography. RESULTS: The transvaginal ethanol sclerotherapy was completed in all cases. The mean long diameter of the cysts was 50 mm (31-100 mm), and the mean operative duration was 22 min (8-45 min). Malignant cells were not isolated from the aspirated fluid in any case. There were no significant intra- or postoperative complications. Two patients (11.1%) had a recurrence at 3 and 32 months after ethanol sclerotherapy, respectively. CONCLUSIONS: Transvaginal ultrasound-guided absolute ethanol sclerotherapy is useful for ovarian endometriotic cysts, particularly in young patients or in patients who would like to become pregnant. However, careful selection based on ultrasonography or magnetic resonance imaging findings and the age of the patients is critical. PMID- 27277729 TI - Hepatic cyst with intracystic bleeding: contrast-enhanced sonographic findings. AB - Intracystic bleeding is a relatively rare complication of hepatic cysts, which is very difficult to diagnose by conventional sonography (US). Hence, a new US technique has been sought for this purpose. We present the case of a hepatic cyst with intracystic bleeding in which contrast-enhanced US showed microbubbles oozing from the cyst wall into the cystic cavity. Contrast-enhanced US is now an important diagnostic tool for diagnosing liver tumors, but contrast-enhanced US findings relating to intracystic bleeding have not been reported. Our observations suggest that this technique may be a useful new diagnostic tool for this purpose. PMID- 27277730 TI - Portal tumor thrombus secondary to gastric carcinoma: report of a case with an emphasis on color Doppler ultrasound findings. AB - We report the case of a 67-year-old woman with portal tumor thrombus (PTT) associated with gastric carcinoma. Abdominal ultrasound (US) revealed a marked thickening of the gastric wall and a mass lesion in the splenic vein. Color Doppler US showed the intraportal mass to be blood flow-poor and revealed a gastroepiploic vein extending from the splenic hilum to the portal confluence, passing behind the peritoneum. These findings corresponded well with gastric carcinoma with PTT. Endoscopy confirmed the presence of an advanced type II carcinoma predominantly located in the upper body, which yielded histological results consistent with a well-differentiated adenocarcinoma. The patient's general condition deteriorated rapidly, and she died 2 months later. To the best of our knowledge, this is the first report describing the presence of a large gastroepiploic vein secondary to gastric carcinoma-associated PTT. PMID- 27277731 TI - Isolated splenic granuloma: report of a case with an emphasis on ultrasound findings. AB - There is a marked paucity of reports on contrast-enhanced ultrasonography (US) for focal splenic disease in the literature, and there are no previously reported contrast-enhanced US findings for splenic granuloma. We report the case of a 77 year-old cirrhotic woman with isolated splenic granulomas. We detail the diagnostic difficulty encountered in this case and briefly review the literature. PMID- 27277732 TI - Papillary fibroelastoma in the left ventricular outflow tract. PMID- 27277734 TI - Standard measurement of cardiac function indexes. PMID- 27277733 TI - A well-demarcated hypervascular round nodule of the pancreas in a patient with a history of nephrectomy. PMID- 27277735 TI - Criteria for the diagnosis of developmental dysplasia of the hip joint. PMID- 27277736 TI - Addressing Deficits and Injustices: The Potential Epistemic Contributions of Patients to Research. AB - Patient or public involvement (PPI) in health research is increasingly expected as a matter of policy. In theory, PPI can contribute both to the epistemic aims intrinsic to research (generating knowledge), and to extrinsically valued features of research such as social inclusion and transparency. In practice, the aims of PPI have not always been clear, although there has been a tendency to encourage the involvement of so-called ordinary people who are regarded as representative of an assumed patient perspective. In this paper we focus on the epistemic potential of PPI, using theoretical work in epistemology to develop a nuanced account of patients' experiential knowledge and how this might contribute directly to conceptual development, hypothesis generation and data interpretation. We also consider how some features of health research pose barriers to this kind of epistemic contribution. Drawing on Miranda Fricker's idea of testimonial injustice, we explore how disciplinary indicators of credibility in clinical and academic health research contexts might be wrongly applied to those involved in PPI, undermining their potential to contribute. Finally we argue for a range of strategies to maximize opportunities for patients to engage with research teams and make epistemologically significant contributions to research. PMID- 27277738 TI - Our new Japanese and English journals serve two different purposes. PMID- 27277737 TI - Medical Need: Evaluating a Conceptual Critique of Universal Health Coverage. AB - Some argue that the concept of medical need is inadequate to inform the design of a universal health care system-particularly an institutional (universal, comprehensive) rather than a residual (minimalist, safety net) system. They argue that the concept (a) contradicts the idea of comprehensiveness; (b) leads to unsustainable expenditures; (c) is too indeterminate for policy; and (d) supports only a prioritarian distribution (and therefore a residual system). I argue (a) that 'comprehensive' understood as 'including the full continuum of care' and 'medically necessary' understood as 'prioritized by medical criteria' are not contradictory, and (b) that UHC is a solution to the problem of sustainability, not its cause. Those who criticize 'medical need' for indeterminacy (c) are not transparent about the source (ethical, semantic, political, or other) of their commitment to their standards of determinacy: they promote standards that are higher than is necessary for legitimate policy, ignoring opportunity costs. Furthermore, the indeterminacy of concepts affects all risk-sharing systems and all systems that rely on medical standard of care. I then argue that (d) the concept of need in itself does not imply a minimal sufficientist standard or a prioritarian distribution; neither does the idea of legitimate public policy dictate that public services be minimalist. The policy choice for a system of health care that is comprehensive and offers as good care as can be achieved when delivered on equal terms and conditions for all is a coherent option. PMID- 27277739 TI - Evaluation of image quality of personal ultrasound imager: Comparison with the conventional machine. AB - OBJECTIVE: To determine if the image quality of a personal ultrasound imager (PUI) is as good as that of a conventional machine (CM). MATERIALS AND METHODS: Ninety patients were studied by the same operator using both the PUI and CM. The quality of the B-mode images obtained from these patients was scored 0, 1 or 2, defined as poor, fair, or good, respectively. Liver-tumor vascularity depicted by power Doppler imaging (PDI) and directional PDI (DPDI) was classified as 0, no blood signal; 1, dot-like blood signal within the tumor; 2, mild blood-flow signal within the tumor; and 3, abundant blood-flow signal within the tumor. RESULTS: The mean score of PUI and CM B-mode image quality was 7.47+/-0.92 and 7.54+/-0.99 (mean+/-SD), respectively (p=0.531). On PDI, grade of vascularity of the liver tumors determined with the PUI was 4.44 and 4.68 in those determined with the CM (p=0.78). On DPDI, tumor vascularity was 3.12 when scored by the PUI and 4.29 when scored with the CM (p=0.03). The qualities of images acquired by the PUI and CM were significantly correlated. CONCLUSION: The quality of B-mode images acquired using the PUI and CM are statistically the same, and they share a similar ability to detect intratumoral blood-flow signals on PDI. Because of its extreme portability, the PUI is expected to become a valuable diagnostic tool in the clinic. PMID- 27277740 TI - Clinical utility of doppler ultrasonography in evaluation of early therapeutic efficacy after transcatheter arterial embolization in patients with hepatocellular carcinoma. AB - This study was undertaken to determine the value of Doppler ultrasonography in the early evaluation of therapeutic efficacy of hepatocellular carcinoma after transcatheter arterial embolization (TAE). Fifty-two nodules in which tumor vascularity had been detected by Doppler ultrasonography before TAE were examined in 41 patients. Doppler signals were evaluated 1 week after TAE, and the results were compared with tumor vascularity as determined by dynamic magnetic resonance imaging (dynamic MRI), which was used as the gold standard. The sonographic signal disappeared in 41 (79%) of the 52 nodules and remained in 11 (21%). All nodules in which intratumor vascularity had been detected showed positive stain to dynamic MRI. Four of 41 nodules in which the sonographic signal disappeard showed positive stain on dynamic MRI. The Sensitivity of Doppler ultrasonography was 73%; specificity, 100%; and accuracy, 92%. Flow signal in deeply (>=5 cm) located small (<3 cm) nodules tended to be more difficult to detect. We conclude that Doppler ultrasonography warrants use after TAE in the early evaluation as a specific and noninvasive imaging technique. PMID- 27277741 TI - A case of double-chambered right ventricle associated with an interventricular septal aneurysm in an elderly patient. AB - Double-chambered right ventricle is a congential malformation caused by an anomalous muscle band obstructing the right ventricular outflow tract. Most reported cases of this condition have been diagnosed in infants, or adolescents. We encountered a 61-year-old woman with a double-chambered right ventricle, associated with a large interventricular septal aneurysm, which is a rare complication. The right ventricular obstruction was corrected with surgery. PMID- 27277742 TI - A case of chronic dissecting aortic aneurysm complicated with rupture into the right atrium: Diagnosis by transesophageal echocardiography. AB - Although rupture of a dissecting aortic aneurysm into the pericardial sac, pleural cavities, or mediastinum is a frequently encountered complication of this entity, rupture into a right-sided cardiac chamber is extremely rare. An 80-year old woman was admitted to this institution because of dyspnea and facial edema. One year before admission, a diagnosis of dissecting aortic aneurysm (Stanford A type) was made based on results of magnetic resonance imaging and transesophageal echocardiography (TEE); however, the patient and her family refused surgical therapy. On admission, blood pressure was 120/60 mmHg, and a Levine 3/6 degrees continuous murmur was audible at the third and fourth intercostal spaces of the right sternal border. Chest x-ray film showed moderate cardiomegaly, congested lung fields, and bilateral pleural effusion. A two-dimensional echocardiogram revealed severe aortic root dilatation 80 mm in diameter with the intimal flap. Color flow Doppler imaging demonstrated abnormal flow toward the back space in dilated ascending aorta. Continuous wave Doppler imaging showed the peak velocity of this flow to be 4.8 m/s. This high-velocity flow strongly suggested that the dissecting aortic aneurysm had ruptured into the right-sided cardiac chamber, and shunt flow from the false lumen of the aortic aneurysm into the right atrium was directly visualized by TEE. Our diagnosis, based on these findings, was chronic dissecting aortic aneurysm with communication into the right atrium. In view of the patient's deteriorating clinical condition, cardiac catheterization was not performed before surgery. Surgery revealed an aneurysm of the ascending aorta measuring 90 mm in diameter and multiple fistulas approximately 2 to 3 mm in diameter arising from the false lumen of the aorta into the right atrium at the base of the atrial appendage. The patient underwent successful replacement of the ascending aorta and closure of the aorto-right atrial fistulas. She had an uneventful postoperative course and was discharged 7 weeks after surgery. PMID- 27277743 TI - Primary carcinoid tumor of the liver: A case report. AB - A53-year-old woman was hospitalized with a hepatic tumor that had been detected on health-screening ultrasonography. Laboratory data showed no marked findings: HBs-Ag and HCV-Ab were negative, and levels of serum AFP, PIVKA-II, CEA, and CA 19-0 were within their normal ranges. Ultrasonogram showed a hyperechoic circle concentric with and inside of a hypoechoic mass in the right hepatic lobe. The tumor appeared isodense with the surrounding liver in unenhanced CT, but enhanced CT showed a low density mass. A celiac arteriogram revealed a hypervascular tumor. The resected tumor measured 20*15 mm. Microscopic findings showed a carcinoid tumor that was positive for Grimelius stain. Further examination of the lung, gastrointestinal tract, and other organs found no primary carcinoid tumor. The patient has been well and free from tumor of the liver or elsewhere for the 7 years since her operation. We therefore considered this lesion to have been a primary carcinoid tumor of the liver. Only 14 cases of this disease have ever been reported in Japan. This report includes a review of the literature on the imaging of this rare tumor. PMID- 27277745 TI - Continuous enzymatic biodiesel production from coconut oil in two-stage packed bed reactor incorporating an extracting column to remove glycerol formed as by product. AB - The transesterification of coconut oil with ethanol catalyzed by Burkholderia cepacia lipase immobilized on polysiloxane-polyvinyl alcohol was performed in a continuous flow. The experimental design consisted of a two-stage packed-bed reactor incorporating a column with cationic resin (Lewatit GF 202) to remove the glycerol formed as by-product and the reactor performance was quantified for three different flow rates corresponding to space-times from 10 to 14 h. The influence of space-time on the ethyl ester (FAEE) concentrations, yields and productivities was determined. The reactor operation was demonstrated for space time of 14 h attaining FAEE concentrations of 58.5 +/- 0.87 wt%, FAEE yields of 97.3 +/- 1.9 % and productivities of 41.6 +/- 1.0 mgester g medium (-1) h(-1). Biodiesel purified samples showed average kinematic viscosity values of 5.5 +/- 0.3 mm(2) s(-1) that meet the criteria established by the American National Standard ASTM (D6751). The immobilized lipase was found to be stable regarding its morphological and catalytic characteristics, showing half-life time (t 1/2) around 1540 h. The continuous packed-bed reactor connected in series with simultaneous glycerol removal has a great potential to attain high level of transesterification yields, raising biodiesel productivity. PMID- 27277746 TI - Difference analysis of the enzymatic hydrolysis performance of acid-catalyzed steam-exploded corn stover before and after washing with water. AB - The difference in the enzymatic hydrolysis yield of acid-catalyzed steam-exploded corn stover (ASC) before and after washing with water reached approximately 15 % under the same conditions. The reasons for the difference in the yield between ASC and washed ASC (wASC) were determined through the analysis of the composition of ASC prehydrolyzate and sugar concentration of enzymatic hydrolyzate. Salts produced by neutralization (CaSO4, Na2SO4, K2SO4, and (NH4)2SO4), sugars (polysaccharides, oligosaccharides, and monosaccharides), sugar-degradation products (weak acids and furans), and lignin-degradation products (ethyl acetate extracts and nine main lignin-degradation products) were back-added to wASC. Results showed that these products, except furans, exerted negative effect on enzymatic hydrolysis. According to the characteristics of acid-catalyzed steam explosion pretreatment, the five sugar-degradation products' mixture and salts [Na2SO4, (NH4)2SO4] showed minimal negative inhibition effect on enzymatic hydrolysis. By contrast, furans demonstrated a promotion effect. Moreover, soluble sugars, such as 13 g/L xylose (decreased by 6.38 %), 5 g/L cellobiose (5.36 %), 10 g/L glucose (3.67 %), as well as lignin-degradation products, and ethyl acetate extracts (4.87 %), exhibited evident inhibition effect on enzymatic hydrolysis. Therefore, removal of soluble sugars and lignin-degradation products could effectively promote the enzymatic hydrolysis performance. PMID- 27277747 TI - Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2 negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK). AB - Endocrine therapy continues to be the optimal systemic treatment for metastatic ER(+)HER2(-) breast cancer. The CDK4/6 inhibitor palbociclib combined with letrozole has recently been shown to significantly improve progression-free survival. Here we examined the cost-effectiveness of this regimen for the Swiss healthcare system. A Markov cohort simulation based on the PALOMA-1 trial (Finn et al. in Lancet Oncol 16:25-35, 2015) was used as the clinical course. Input parameters were based on summary trial data. Costs were assessed from the Swiss healthcare system perspective. Adding palbociclib to letrozole (PALLET) compared to letrozole monotherapy was estimated to cost an additional CHF342,440 and gain 1.14 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio (ICER) of CHF301,227/QALY gained. In univariate sensitivity analyses, no tested variation in key parameters resulted in an ICER below a willingness-to-pay threshold of CHF100,000/QALY. PALLET had a 0 % probability of being cost effective in probabilistic sensitivity analyses. Lowering PALLET's price by 75 % resulted in an ICER of CHF73,995/QALY and a 73 % probability of being cost effective. At current prices, PALLET would cost the Swiss healthcare system an additional CHF155 million/year. Palbociclib plus letrozole cannot be considered cost-effective for the first-line treatment of patients with metastatic breast cancer in the Swiss healthcare system. PMID- 27277749 TI - Clinical significance of RET mutation screening in a pedigree of multiple endocrine neoplasia type 2A. AB - The clinical characteristics and RET proto-oncogene (RET-PO) mutation status of a patient with multiple endocrine neoplasia type 2A pedigree (MEN2A) was analyzed with the aim of preliminarily exploring the molecular mechanisms and clinical significance of the disease. Clinical characteristics of a single MEN2A patient were analyzed. Genomic DNA was extracted from the peripheral blood of the proband and 10 family members. The 21 exons of RET-PO were PCR amplified and the amplified products were sequenced. Of the family members, 5 exhibited a C634Y (TGC->TAC) missense mutation in exon 11 of RET-PO, among which 2 family members were screened as mutation carriers, while the others did not exhibit clinical symptoms of the mutation. The screening and analysis of RET-PO mutations for the MEN2A proband and the family members suggests potential clinical phenotypes and enables assessment of the risk of disease development, thus providing useful information for determining the surgical timing of preventive thyroid gland removal. PMID- 27277748 TI - The structural alteration of gut microbiota in low-birth-weight mice undergoing accelerated postnatal growth. AB - The transient disruption of gut microbiota in infancy by antibiotics causes adult adiposity in mice. Accelerated postnatal growth (A) leads to a higher risk of adult metabolic syndrome in low birth-weight (LB) humans than in normal birth weight (NB) individuals, but the underlying mechanism remains unclear. Here, we set up an experiment using LB + A mice, NB + A mice, and control mice with NB and normal postnatal growth. At 24 weeks of age (adulthood), while NB + A animals had a normal body fat content and glucose tolerance compared with controls, LB + A mice exhibited excessive adiposity and glucose intolerance. In infancy, more fecal bacteria implicated in obesity were increased in LB + A pups than in NB + A pups, including Desulfovibrionaceae, Enterorhabdus, and Barnesiella. One bacterium from the Lactobacillus genus, which has been implicated in prevention of adult adiposity, was enhanced only in NB + A pups. Besides, LB + A pups, but not NB + A pups, showed disrupted gut microbiota fermentation activity. After weaning, the fecal microbiota composition of LB + A mice, but not that of NB + A animals, became similar to that of controls by 24 weeks. In infancy, LB + A mice have a more dysbiotic gut microbiome compared to NB + A mice, which might increase their risk of adult metabolic syndrome. PMID- 27277750 TI - Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells. AB - Combination therapy using anticancer drugs and nucleic acid is a more promising strategy to overcome multidrug resistance in cancer and to enhance apoptosis. In this study, lipid-polymer hybrid nanoparticles (LPNs), which contain both pemetrexed and miR-21 antisense oligonucleotide (anti-miR-21), have been developed for treatment of glioblastoma, the most aggressive type of brain tumor. Prepared LPNs have been well characterized by particle size distribution and zeta potential measurements, determination of encapsulation efficiency, and in vitro release experiments. Morphology of LPNs was determined by transmission electron microscopy. LPNs had a hydrodynamic size below 100 nm and exhibited sustained release of pemetrexed up to 10 h. Encapsulation of pemetrexed in LPNs increased cellular uptake from 6% to 78%. Results of confocal microscopy analysis have shown that co-delivery of anti-miR-21 significantly improved accumulation of LPNs in the nucleus of U87MG cells. Nevertheless, more effective cytotoxicity results could not be obtained due to low concentration of anti-miR-21, loaded in LPNs. We expect that the effective drug delivery systems can be obtained with higher concentration of anti-miR-21 for the treatment of glioblastoma. PMID- 27277751 TI - [Phakic intraocular lenses]. AB - Refractive surgical procedures are generally divided into additive procedures with, e. g. implantation of an artificial lens and subtractive procedures with ablation of corneal tissue. In this article the current status of phakic intraocular lens (IOL) implantation for correction of refractive errors is reviewed. Phakic IOLs are constructed as angle-supported or iris-fixated anterior chamber lenses and sulcus-fixated posterior chamber lenses. The implantation of phakic IOLs has been demonstrated to be an effective, safe, predictable and stable procedure to correct higher refractive errors. Complications are rare and depend to a large extent on the location. For anterior chamber lenses the main concern is critical endothelial cell loss and for posterior chamber lenses early cataract formation. PMID- 27277752 TI - [The IRIS(r) Registry : Purpose and perspectives. German Version]. AB - The American Academy of Ophthalmology IRIS(r) Registry (Intelligent Research in Sight) launched about 2 years ago and has already become the largest national clinical specialty data registry with nearly 50 million patient visits and over 14 million unique patients. The purpose of the registry is to support and promote continued improvement in the delivery of eye care. The perspectives that "big data" encompass are the key issues facing ophthalmology and eye care, including public health and public policy concerning disease incidence and prevalence, utilization of eye care services, natural history of disease, disease surveillance, comparative effectiveness, safety and adverse event monitoring, compliance with "best practices" and clinical guidelines, etc. The valuable real world and current-day insights provided by the IRIS Registry and other registries like it will accelerate scientific learning and improvements in care delivery, particularly in a cost-constrained environment. PMID- 27277753 TI - Examination of the importance of age of onset, callous-unemotional traits and anger dysregulation in youths with antisocial behaviors. AB - Age of onset, callous-unemotional (CU) traits and anger dysregulation have separately been proposed as relevant factors in explaining the heterogeneity of antisocial behaviour (ASB). Taking a dimensional perspective, this study examined the specific contributions and the mutual influences (i.e., interactions) of these three characteristics on specific dimensions of ASB (i.e., criminal behaviours and externalizing symptoms). Assessments were conducted on 536 youths from institutions with the youth psychopathic traits inventory (CU traits), the Massachusetts youth screening instrument-second version (anger dysregulation), the criminology questionnaire (criminal behaviours) and the child behavior checklist (externalizing symptoms), rated by both the youths and their carers. Using Bayes as estimators, the results revealed that the number and frequency of crimes (and, more specifically, damage to property, property offenses and media crimes) were explained by a specific contribution of each factor (age of onset, CU traits and anger dysregulation). Additionally, the interactions between age of onset and CU traits or anger dysregulation were relevant predictors of some types of crimes (i.e., damage to property, property offences and media crimes). Furthermore, when rated by youths, externalizing symptoms were explained by CU traits and anger dysregulation. However, when rated by the carer, anger dysregulation was more important in explaining externalizing symptoms. This study highlights the importance of considering these factors altogether and the value of using a dimensional perspective when examining the structure of ASB in youths. Consequently, future classifications should take into account the mutual account of these characteristics, which were previously studied separately. PMID- 27277754 TI - An initial study of family accommodation in children and adolescents with chronic tic disorders. AB - This initial study examined the nature, incidence, and clinical correlates of family accommodation in youth with tic disorders, and validated a brief self report measure of tic-related family accommodation, the Tic Family Accommodation Scale (TFAS). Seventy-five youth aged 6-18 who were diagnosed with a tic disorder and their parent completed a diagnostic clinical interview, and clinician and parent-report measures of tic severity, depressive symptoms, anxiety symptoms, behavioral problems, family accommodation and impairment. An exploratory factor analysis of the TFAS showed a two-factor structure, with good internal consistency for the Total score, Modification of Child Environment and Modification of Parent Environment subscales (alpha = 0.88, 0.86, and 0.81, respectively). Family accommodation was not associated with tic severity. Family accommodation was associated with increased anxiety and depressive symptoms, higher externalizing, rule breaking, aggressive behaviors and social problems, and with greater tic-related functional impairment. Anxiety and externalizing problems (but not depressive symptoms) predicted family accommodation when controlling for tic severity. Family accommodation predicted high levels of functional impairment over and above the effect of tic severity, anxiety, depression and externalizing problems. Family accommodation is a common phenomenon for youth with tic disorders, with modifications typically encompassing changes to the child and/or parent environments. Accommodation was not associated with tic severity, but was related to higher levels of anxiety, depressive symptoms, externalizing symptoms, aggression, and rule breaking behaviors. Results suggest that other emotional symptoms are more likely to drive accommodation practices than the tic symptoms per se. PMID- 27277755 TI - Magnetofection based on superparamagnetic iron oxide nanoparticle-mediated low lncRNA HOTAIR expression decreases the proliferation and invasion of glioma stem cells. AB - Glioma stem cells (GSCs) are a special subpopulation of glioma cells that are key to the sensitivity of tumors to treatments and to the possibility of tumor recurrence. Identifying new strategies that inhibit the growth of GSCs are therefore important for developing novel therapies for glioblastoma multiforme (GBM). In this study, CD133+ human glioma stem cells were isolated and cultured. Magnetic nanoparticles were used to mediate the expression of siRNAs targeting the HOTAIR (si-HOTAIR) sequence in human gliomas. Effect of downregulation of HOTAIR expression on proliferation, invasion and in vivo tumorigenicity of human GSCs and underlying molecular mechanisms were further evaluated. The results of the MTT assay and flow cytometric analysis showed that downregulation of HOTAIR expression inhibited cell proliferation and induced cell cycle arrest. Transwell assays demonstrated that downregulation of HOTAIR expression resulted in a decrease in the invasive capability of GSCs. Moreover, magnetic nanoparticle mediated low expression of HOTAIR effectively reduced the tumorigenic capacity of glioma stem cells in vivo. In addition, the results of qRT-PCR and western blot analysis demonstrated that downregulation of HOTAIR expression significantly increased the expression of PDCD4 in GSCs, in addition to reducing the expression of CCND1 and CDK4. An in-depth mechanistic analysis showed that downregulation of HOTAIR expression reduced the recruitment of downstream molecules, EZH2 and LSD1, thereby activating the expression of PDCD4 at the transcriptional level. In conclusion, downregulation of HOTAIR expression effectively promoted the expression of PDCD4, thereby inhibiting the proliferation, invasion and in vivo tumorigenicity of human GSCs. PMID- 27277756 TI - Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients. AB - To test the hypothesis that irradiated volume of specific subregions of pelvic active bone marrow as detected by (18)FDG-PET may be a predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation, we analyzed 44 patients submitted to IMRT and concurrent chemotherapy. Several bony structures were defined: pelvic and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. Active BM was characterized employing (18)FDG PET and characterized in all subregions as the volume having standard uptake values (SUVs) higher than SUVmean. All other regions were defined as inactive BM. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hb) and platelet (Plt) nadirs. Generalized linear modeling was used to find correlations between dosimetric variables and blood cells nadirs. WBC nadir was significantly correlated with LSBM mean dose (beta = -1.852; 95 % CI -3.205/ 0.500; p = 0.009), V10 (beta = -2.153; 95 % CI -4.263/-0.721; p = 0.002), V20 (beta = -2.081; 95 % CI -4.880/-0.112; p = 0.003), V30 (beta = -1.971; 95 % CI 4.748/-0.090; p = 0.023) and IBM V10 (beta = -0.073; 95 % CI -0.106/-0.023; p = 0.016). ANC nadir found to be significantly associated with LSBM V10 (beta = 1.878; 95 % CI -4.799/-0.643; p = 0.025), V20 (beta = -1.765; 95 % CI -4.050/ 0.613; p = 0.030) and IBM V10 (beta = -0.039; 95 % CI -0.066/-0.010; p = 0.027). Borderline significance was found for correlation between Plt nadir and LSBM V30 (beta = -0.056; 95 % CI -2.748/-0.187; p = 0.060), V40 (beta = -0.059; 95 % CI 3.112/-0.150; p = 0.060) and IBM V30 (beta = -0.028; 95 % CI -0.074/-0.023; p = 0.056). No inactive BM subsites were found to be correlated with any blood cell nadir. (18)FDG-PET is able to define active bone marrow within pelvic osseous structures. LSBM is the strongest predictor of decreased blood cells nadirs in anal cancer patients undergoing concurrent chemoradiation. PMID- 27277758 TI - Relationship between Fas and Fas Ligand gene polymorphisms and pre-eclampsia. AB - AIM: In normal pregnancy, the Th1 subtype, responsible for the production of inflammatory cytokines, is reduced, and the Th2 subtype is increased to prohibit inflammation. In pre-eclampsia, the Th1 cell population is increased; thus, subsequent inflammation and trophoblast destruction occur. Polymorphisms in the Fas and Fas Ligand (FasL) promoter regions can influence Fas and FasL expression and accused to increase of Th1 subtype. METHODS: DNA samples from 153 pregnant women with pre-eclampsia and 140 controls were genotyped through polymerase chain reaction-restriction fragment length polymorphism. A Fisher's exact test was used to compare the distribution of individual polymorphisms. RESULTS: Fas-1377 AA, AG and GG genotypes were observed in 2.61%, 18.30% and 79.08% in the pre-eclampsia group opposed to 0%, 27.14% and 72.85% in the control group (P = 0.037), respectively. Fas-670 AA, AG and GG genotypes were observed in 37.9%, 41.8% and 20.3% of pre-eclampsia patients compared with 33.6%, 50.7% and 15.7% in healthy pregnant women (P = 0.291), respectively. No statically significant differences in the FasL-844 genotype were observed between the groups (P = 0.69). CONCLUSION: The Fas-1377G > A polymorphism is associated with a higher risk of pre-eclampsia. PMID- 27277757 TI - Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo. AB - Ovarian cancer is the leading cause of death among gynecological malignancies, and high grade serous ovarian carcinoma is the most common and most aggressive subtype. Recently, it was demonstrated that cAMP mediates protein kinase A independent effects through Epac (exchange protein directly activated by cAMP) proteins. Epac proteins, including Epac1 and Epac2, are implicated in several diverse cellular responses, such as insulin secretion, exocytosis, cellular calcium handling and formation of cell-cell junctions. Several reports document that Epac1 could play vital roles in promoting proliferation, invasion and migration of some cancer cells. However, the expression levels and roles of Epac1 in ovarian cancer have not been investigated. In the present study, we detected the expression levels of Epac1 mRNA and protein in three kinds of ovarian cancer cells SKOV3, OVCAR3 and CAOV3. Furthermore, the effect of Epac1 knockdown on the proliferation and apoptosis of SKOV3 and OVCAR3 cells was evaluated in vitro and in vivo. The results showed that there was higher expression of Epac1 mRNA and protein in SKOV3 and OVCAR3 cells. Epac1 knockdown inhibited the proliferation of SKOV3 and OVCAR3 cells in vitro and in vivo. Decreased proliferation may be due to downregulation of Epac1-induced G1 phase arrest by inactivating the AKT/Cyclin D1/CDK4 pathway, but not to alterations in the MAPK pathway or to apoptosis. Taken together, our data provide new insight into the essential role of Epac1 in regulating growth of ovarian cancer cells and suggest that Epac1 might represent an attractive therapeutic target for treatment of ovarian cancer. PMID- 27277760 TI - Right atrial aneurysm with downward displacement of the anterior leaflet that resembled Ebstein's anomaly. AB - A 13-year-old boy presented with right atrial aneurysm and downward displacement of the anterior leaflet in the tricuspid valve into the right ventricle, without tricuspid valve regurgitation. Paroxysmal atrial flutter was caused by an abnormal electrical re-entry circuit, which could not be treated using catheter radiofrequency ablation. Therefore, the patient underwent surgical ablation and resection of the enlarged right atrial wall. The anterior leaflet of the tricuspid valve was plastered and displaced downward into the right ventricle, which resembled Ebstein's anomaly. Pathological evaluation revealed a thin wall that contained fibrous tissue with lipomatous degeneration and few muscular elements. No postoperative arrhythmia was observed. PMID- 27277759 TI - Longitudinal Associations Between Parental Monitoring Discrepancy and Delinquency: An Application of the Latent Congruency Model. AB - Studies have shown that discrepancies (relative concordance or discordance) between parent and adolescent ratings are predictive of problem behaviors; monitoring, in particular, has been consistently linked to them. The current study tested whether discrepancies in perceptions of maternal monitoring, rated by mothers and youth at age 12, foretold delinquency (rule breaking) at age 15, and whether parental closeness and conflict predicted higher discrepancies, and indirectly, higher delinquency. The final study sample used the NICHD longitudinal dataset with N = 966 youth (50.1 % female) and their mothers (80.1 % European American, 12.9 % African American, 7 % other ethnicity). The analytic approach consisted of an extension and application of the Latent Congruency Model (LCM) to estimate monitoring discrepancies as well as age 15 delinquency scores. Findings showed that age 12 monitoring discrepancy was predictive of age 15 delinquency for both boys and girls based on youth reports, but not for maternal reports. Age 11 closeness predicted age 12 monitoring discrepancy, which served as a mediator for its effect on age 15 adolescent-reported delinquency. Thus, based on the rigorous LCM analytic approach which seeks to minimize the effects by competing explanations and to maximize precision in providing robust estimates, rates of perceived discordance in parenting behaviors during early adolescence matter in understanding variability in adolescent delinquency during middle adolescence. PMID- 27277761 TI - Postoperative pyothorax a risk factor for acute exacerbation of idiopathic interstitial pneumonia following lung cancer resection. AB - OBJECTIVE: Acute exacerbation (AE) of idiopathic interstitial pneumonia (IP) is a potentially fatal postoperative complication following lung cancer resection. Postoperative pyothorax (PP) following development of a bronchopleural fistula (BPF) after lung surgery induces continuous inflammation and may affect the occurrence of AE. We investigated the relationship between AE and PP in patients who underwent pulmonary resection for lung cancer. METHODS: A total of 941 patients who underwent lung resection due to primary lung cancer from 2006 to 2015 at our hospital were investigated. RESULTS: Of the 941 enrolled patients, 137 (14.6 %) had idiopathic IP and were predominantly male (p < 0.01). Pathological stage Ia and adenocarcinoma were observed at significantly high rates in the non-IP group (p < 0.01). Patients with IP showed a tendency for a higher percentage of PP (p = 0.054). Of the 137 patients with IP, 17 (12.4 %) showed postoperative AE. Furthermore, PP was observed in three cases in the AE(+) group and two in the AE(-) group. PP had a correlation with a significantly higher incidence of AE (p = 0.007). CONCLUSION: PP was found to be a significant risk factor for postoperative AE in lung cancer patients undergoing a pulmonary resection. Since IP itself is likely a risk factor for PP, prevention of BPF is important for patients with IP, as it can lead to PP. PMID- 27277764 TI - Separate from essential meaning but still important: space, colons and dashes. PMID- 27277763 TI - Female doctors in US earn much less than male doctors, study finds. PMID- 27277762 TI - Influence of alcohol and other substances of abuse at the time of injury among patients in a Norwegian emergency department. AB - BACKGROUND: The presence of alcohol or other substances of abuse in blood or urine from injured patients is often used as a proxy for substance influence at the time of injury. The aim of this study was to obtain an estimate of substance influence at the time of injury based on blood concentrations of alcohol and other substances of abuse, and to explore the relationship between the substance prevalence at the time of admittance to the hospital and the actual influence at the time of the injury. METHODS: The study included all adult patients admitted to the emergency department of a university hospital during 1 year (n = 996). Quantification in blood was done by an enzymatic method for alcohol, and by liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry for 28 other substances of abuse. Concentrations of alcohol and other substances in blood at the time of injury were calculated. The degree of influence was assessed on the basis of the calculated blood concentrations, with a threshold of influence set at a blood alcohol concentration (BAC) of 0.05 %, or a substance concentration leading to an influence similar to that of a BAC of 0.05 %. RESULTS: A total of 324 patients (32.5 %) were determined to be under the influence at the time of injury. In comparison, 394 patients (39.6 %) had one or more substances above the cut-off limit in blood at the time of admittance to the hospital. Alcohol was the most prevalent substance causing influence at 25.9 %. Among patients with violence-related injuries, almost 75 % were under the influence of alcohol and/or substances. Patients under the influence were younger, and men were more often under the influence than women. More patients were under the influence at nighttime and during weekends than at daytime and on weekdays. CONCLUSIONS: About one third of the injured patients were determined to be under the influence at the time of injury, with alcohol being the most prevalent substance causing influence. Approximately 98 % of the patients with alcohol detected in blood at the time of admittance to the hospital were under the influence of alcohol at the time of injury. PMID- 27277765 TI - Dual-frequency ultrasound activation of nanomicellar doxorubicin in targeted tumor chemotherapy. AB - INTRODUCTION: This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice. METHODS: We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two (T 2) and five (T 5) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. RESULTS: The results of the combination of frequencies 28 kHz (0.04 W/cm(2)) and 3 MHz (2.00 W/cm(2)) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication (P < 0.05). The micellar doxorubicin injection with sonication group showed a significant difference in the relative volume percent parameter compared with the other groups (P < 0.05). Additionally, the T 2 and T 5 times in the micellar doxorubicin with sonication group were significantly higher than in the other groups (P < 0.05). Also, the survival period of the mice in the micellar doxorubicin with sonication group was significantly longer than in the other groups (P < 0.05). These findings were verified histopathologically. CONCLUSION: This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is effective in producing cavitation activity at low intensity. We conclude that dual-frequency sonication with micellar doxorubicin injection extends survival in a murine breast adenocarcinoma model. PMID- 27277766 TI - Expanding aliasing limit in measurement of tissue velocity using autocorrelation method. AB - Autocorrelation using in-phase and quadrature (IQ) signals suffers from aliasing when the velocity of rapidly moving tissue, such as the heart wall, is measured. In the present study, a simple method was proposed to expand the aliasing limit. In the proposed method, the velocity difference between two successive frames (corresponding to acceleration) of tissue was also estimated directly from IQ signals. When aliasing occurs in the velocity in the current frame, which was estimated from IQ signals, the velocity in the current frame was corrected by adding the velocity difference to the velocity in the previous frame. Using this procedure, the velocity can be estimated if the difference between velocities in the current and previous frames is less than the aliasing limit. The velocity of the posterior heart wall in the longitudinal-axis view of about 0.08 m/s could be estimated under the aliasing limit of the conventional autocorrelation method of 0.047 m/s. Myocardial velocity over the conventional aliasing limit could be measured by the proposed method. PMID- 27277767 TI - Effects of horizontal console position on operator muscular stress during abdominal ultrasonic diagnosis. AB - Ultrasound examinations may require sonographers to adopt unnatural postures, which can lead to musculoskeletal disorders. We previously assessed the effect of a vertical operation panel on muscular stress. In this study, we focused on the horizontal positioning of the control panel of a diagnostic ultrasound system to quantitatively assess the influence of work plane position on musculoskeletal stress during scanning. Five subjects were asked to perform a simulated scanning task that involved touching five points on the control panel, with the work plane set at different positions in space. Electromyograms of each part of the body and wrist joint angles indicated that the least stressful position of the left hand was about 350 mm from the center of the trunk in the longitudinal (front-back) direction and 100 mm left of the center of the trunk in the lateral (right-left) direction. PMID- 27277768 TI - Erratum to: Effects of horizontal console position on operator muscular stress during abdominal ultrasonic diagnosis. PMID- 27277769 TI - Dynamic changes in ultrasound characteristics of nodules in cirrhotic liver and their implications in surveillance for malignancy. AB - OBJECTIVE: To investigate whether there are ultrasound characteristics that can suggest HCC in ultrasound surveillance of nodules in cirrhotic liver. METHODS: Data from 277 patients with hepatitis B virus-related nodules in cirrhotic liver undergoing ultrasound surveillance of the nodules for malignancy were reviewed. Size of the nodules ranged 6-23 mm. The nodules were followed by color Doppler ultrasound at 3- to 6-month intervals, with focus on size, shape, echogenicity, margin, halo sign, and vasculature. Suspicious malignant nodules underwent contrast-enhanced CT/MRI, and some indeterminate nodules underwent biopsy. RESULTS: Nodules in 189 patients were hypo/isoechoic/faint high echoic, 23 were hyperechoic, and 65 were both hypo/isoechoic/faint high echoic and hyperechoic. Forty-two patients developed hepatocellular carcinoma: 35 from nodules and 7 from background parenchyma. Fourteen nodules recessed (size >10 mm), 11 new nodules emerged (size >10 mm), and the total number of nodules increased over 5 years. All hepatocellular carcinomas developed from hypo/isoechoic/faint high echoic nodules, and no typical hyperechoic nodules developed into hepatocellular carcinomas. The size increased significantly when the nodules developed into hepatocellular carcinomas. No nodule presented an overt halo, seven hepatocellular carcinomas developed from nodules with a halo, and ill-defined margins of 16 nodules became well defined when they developed into hepatocellular carcinomas. No vasculature was detectable in the nodules, while it was detectable in eight hepatocellular carcinomas. No significant change occurred in nodules without malignancy. CONCLUSION: The characteristics for dynamic surveillance of nodules in cirrhotic liver for malignancy should include nodule growth, margin, halo, and vasculature. Apart from evident growth, an ill-defined margin becoming a well-defined margin, a newly emerged halo, and newly detectable vasculature are strongly suggestive of nodule malignancy. PMID- 27277770 TI - Pimobendan improves right ventricular myocardial contraction and attenuates pulmonary arterial hypertension in rats with monocrotaline-induced pulmonary arterial hypertension. AB - PURPOSE: The present study aimed to evaluate the therapeutic effect of pimobendan treatment for pulmonary hypertension (PH) in rats administered monocrotaline (MCT). METHODS: Fifty-four 12-week-old male Sprague-Dawley rats were injected with monocrotaline or saline solution. Serial echocardiography and right ventricular systolic pressure (RVSP) measurement via a cardiac catheter were performed. After injection of MCT, rats received oral pimobendan (MCT/pimobendan group) or no treatment (MCT group) until undergoing echocardiography and cardiac catheter insertion. RESULTS: Right ventricular systolic pressure in the MCT/pimobendan group was lower than that in the MCT group at 6 weeks. Right ventricle free wall (RVFW) myocardial systolic velocity (Sm) in the MCT group showed a reduction compared with the saline group at 2 weeks. RVFW Sm in the MCT/pimobendan group was preserved as compared with the saline group at 2 weeks. RVFW Tei index in the MCT/pimobendan group showed a reduction compared with the saline group and the MCT group at 2 weeks. Echocardiography in the MCT/pimobendan group showed improvement compared with MCT rats. CONCLUSIONS: Both a reduction in RVSP and improvement in myocardial contraction were demonstrated with administration of pimobendan in rats with PH induced by MCT. Echocardiography evaluation of systolic function seems to be useful for monitoring excess administration of pimobendan. PMID- 27277771 TI - HDlive rendering image of adnexal tumors: preliminary report. AB - BACKGROUND: Our objective is to present our first experience of adnexal tumors reconstructed employing the HDlive rendering mode. METHODS: Seven adnexal tumors (one case each of chocolate cyst, benign cystic teratoma, serous cystadenofibroma, and torsion of the hydrosalpinx, and three cases of ovarian cancer) were studied using the HDlive rendering mode. RESULTS: In the case of the chocolate cyst, the smooth inner wall with numerous tiny projections was clearly identified. In the case of benign cystic teratoma, a smooth hair ball inside the cyst was evident. In the case of the serous cystadenofibroma, a smooth, solid projection and relatively smooth septum were noted. In the three cases of ovarian cancer, numerous irregular papillae and irregular, thick septae were depicted. In the case of the bilateral hydrosalpinx with torsion of the right tube, different fluid contents were recognized. CONCLUSION: The HDlive rendering mode provides anatomically realistic features such as macroscopic specimens for physicians and pathologists due to the complete depiction of the inner surface of the adnexal tumors. PMID- 27277772 TI - Long-term investigation of kidney ultrasound in cases of hemolytic uremic syndrome in children. AB - PURPOSE: The aim is to describe the changes in initial findings of kidney ultrasound examinations in cases of hemolytic uremic syndrome (HUS) in children and to evaluate the respective importance of three sonographical parameters: echogenicity, corticomedullary differentiation (CMD), and kidney size. The correlation with laboratory parameters and proteinuria is analysed. METHODS: Reports containing ultrasound examinations and laboratory values from 1989 through 2012 of 39 children (13 cases of atypical HUS and 26 cases of typical HUS, first diagnosis at age 4 months to 10 2/12 years) suffering from HUS were analysed retrospectively. Ultrasound scans of the right kidney (n = 312) were evaluated with regard to the factors echogenicity, CMD, and kidney volume (ml, percentile). Laboratory parameters included serum creatinine, endogenous creatinine clearance in 24-h urine collection, eGFR according to Schwartz, and the protein content of the 24-h urine collection. RESULTS: All patients initially had increased echogenicity of the kidneys. All kidney volumes were ranged in the higher percentiles (the median percentile was the 85th). For assessment of long term progression, the echogenicity proved to be of higher importance than the CMD due to a significant correlation between laboratory parameters of kidney function and the echogenicity. CONCLUSION: Ultrasound examination of the kidneys is an important method in follow-up examinations of patients with HUS. Renal morphology correlates with laboratory parameters of kidney function. PMID- 27277773 TI - Utility of three-dimensional transthoracic echocardiography in diagnosis of intermediate atrioventricular septal defect: report of an adult case. AB - We present the case of a 54-year-old male with an intermediate atrioventricular septal defect (AVSD). He was referred to our institute for treatment of shortness of breath. Two-dimensional transthoracic echocardiography demonstrated an ostium primum defect of the atrial septum, a common atrioventricular valve with mild regurgitations, and an interventricular communication, which are the features of complete AVSD. However, three-dimensional transthoracic echocardiography (3D-TTE) could clearly visualize the tricuspid pouch (i.e., persistence of the tissue in the endocardial cushion), a feature of partial AVSD. 3D-TTE appears to be a useful modality for diagnosis of intermediate AVSD. PMID- 27277774 TI - A case of solitary bile duct hamartoma with advanced gastric carcinoma: findings in contrast-enhanced ultrasonography. AB - Bile duct hamartomas (BDH), which are also known as von Meyenburg complexes, are benign neoplasms that involve cystic dilatation of the bile duct surrounded by fibrous stroma. However, multiple lesions develop in most cases of BDH, whereas a solitary lesion, as seen in our case, is relatively rare. We report here the co existence of gastric carcinoma and BDH mimicking metastasis in a 30-year-old woman. A lesion measuring 13 * 9 mm with the appearance of a hyperechoic nodule with no pulsatile blood flow signals was observed on US and Doppler US in S4 of the liver. On contrast-enhanced ultrasonography (CEUS), the septum-like structure in the tumor was weakly enhanced at 17 s after administration of Sonazoid. There has been no description of solitary BDH findings on CEUS in the literature. We present the US findings of BDH, including those yielded by CEUS using Sonazoid, along with the microscopic pathological correlation. PMID- 27277775 TI - Hemodynamic changes during balloon-occluded transarterial chemoembolization (B TACE) of hepatocellular carcinoma observed by contrast-enhanced ultrasound. AB - Balloon-occluded transarterial chemoembolization (B-TACE) is able to achieve denser accumulation of Lipiodol emulsion (LE) in hepatocellular carcinoma (HCC) than conventional TACE. However, to maximize the therapeutic effect of B-TACE, it is imperative to understand the hemodynamic changes that occur during arterial occlusion. We here present two patients with HCC in whom the hemodynamic changes during arterial occlusion were depicted and evaluated by contrast-enhanced ultrasound (CEUS). Arterial flow beyond the catheter tip was observed by CEUS even after balloon occlusion. In one patient, a reduction in arterial blood flow in the HCC was observed by CEUS during balloon occlusion of the target area for embolization. After B-TACE, dense LE accumulation in the HCC nodule was confirmed by flat-panel detector CT, indicating an excellent therapeutic effect. In the other patient, no changes in arterial blood flow in the HCC nodule were observed by CEUS during balloon occlusion of the target area for embolization. After B TACE, intermediate LE accumulation in the HCC nodule was confirmed by flat-panel detector CT, indicating an incomplete therapeutic effect. The findings obtained in the two patients presented here suggest that B-TACE can be performed more effectively and reliably by monitoring blood flow using CEUS. PMID- 27277776 TI - Associated gastroduodenal artery aneurysm aortic aneurysm: the diagnostic contribution of contrast-enhanced ultrasound in correlation with computed tomography angiography. AB - Splanchnic aneurysms are rare conditions, with localization at the level of the gastroduodenal artery being encountered in only 1.5 % of the cases. Due to the high mortality risk, early detection and optimal treatment are required. We stress the importance of ultrasonography as a primary method of detection as well as the role of contrast-enhanced ultrasound in characterization of visceral aneurysms. Due to its noninvasive nature, the examination could be used for follow-up after therapeutic procedures or in cases were a curative intervention is not possible. PMID- 27277777 TI - Percutaneous radiofrequency ablation for treatment of giant cell tumor of bone guided by real-time US fused with CT. AB - Radiofrequency ablation (RFA) is a well-established technique for the treatment of soft tissue tumors of the liver and kidney that has increasingly been used for both benign and malignant bone tumors, such as giant cell tumor of bone (GCT). Reports in the literature pertaining to RFA for GCT have involved computed tomography (CT)-guided RFA, which presents several drawbacks such as radiation, lack of real-time monitoring, and the fact that it may be time-consuming. We report a case of GCT treated with percutaneous RFA using ultrasound guidance with CT fusion, which offers a simple, real-time guidance solution without radiation. PMID- 27277778 TI - Imaging and surgical approach for a schwannoma of the hand. AB - Schwannomas are benign encapsulated neoplasms of the peripheral nerve sheath. Clinical diagnosis is often difficult, and final diagnosis is usually based on histopathological findings. Imaging techniques, such as magnetic resonance imaging and ultrasonography, can be optimized to improve assessment prior to surgical treatment. The present case demonstrates that high-resolution sonography can be useful in assessing the underlying cause of median nerve pathology. PMID- 27277779 TI - Follicular thyroid carcinoma with predominantly cystic formation presenting initially with multiple distant metastases. AB - Primary malignancies presenting with multiple distant metastases include lung cancer, gastrointestinal malignancy, breast cancer, and prostatic cancer. Multiple distant metastases from follicular thyroid carcinoma (FTC) are uncommon. Cystic formation in FTC is an atypical finding in ultrasonography. The cystic formation of a thyroid nodule is usually considered a benign sonographic finding. We report the case of a 78-year-old man who presented with multiple distant metastases from an FTC with a predominantly cystic formation. PMID- 27277780 TI - Radiofrequency ablation of parathyroid adenoma in primary hyperparathyroidism. AB - We present a case of a 32-year-old woman with hyperparathyroidism, treated with ultrasound-guided percutaneous radiofrequency ablation (RFA). RFA, assisted by saline injection inferomedial to the parathyroid, is a safe technique that prevents burn injury to the nerve. The saline injection technique shifted the parathyroid gland laterally, so that the distance between the nerve and the parathyroid gland was sufficient to prevent burn injury. The completeness of tissue ablation was evaluated based on Doppler ultrasound imaging and serum intact parathyroid hormone (iPTH) level immediately after RFA. There were no complications associated with RFA. Serum iPTH levels normalized during follow-up for 20 months. It was possible to perform RFA for primary parathyroid adenoma safely using a saline injection technique. PMID- 27277781 TI - Three- and four-dimensional sonographic diagnosis of fetal intra-abdominal umbilical vein varix. PMID- 27277782 TI - Active bleeding revealed by contrast-enhanced ultrasonography: beyond the abdominal cavity. PMID- 27277783 TI - Structure of the pulmonary hydatid cyst. PMID- 27277784 TI - Pericyst shell or absent pericyst layer in the brain hydatid cyst? PMID- 27277785 TI - Differentiation of renal cell carcinomas from other renal mass lesions. PMID- 27277786 TI - Introduction to indexes for cardiac resynchronization therapy (CRT) indication. PMID- 27277788 TI - Temporary severe bradycardia due to pacemaker programming. PMID- 27277789 TI - Temporary severe bradycardia due to pacemaker programming. PMID- 27277787 TI - Coordination of the recruitment of the FANCD2 and PALB2 Fanconi anemia proteins by an ubiquitin signaling network. AB - Fanconi anemia (FA) is a chromosome instability syndrome and the 20 identified FA proteins are organized into two main arms which are thought to function at distinct steps in the repair of DNA interstrand crosslinks (ICLs). These two arms include the upstream FA pathway, which culminates in the monoubiquitination of FANCD2 and FANCI, and downstream breast cancer (BRCA)-associated proteins that interact in protein complexes. How, and whether, these two groups of FA proteins are integrated is unclear. Here, we show that FANCD2 and PALB2, as indicators of the upstream and downstream arms, respectively, colocalize independently of each other in response to DNA damage induced by mitomycin C (MMC). We also show that ubiquitin chains are induced by MMC and colocalize with both FANCD2 and PALB2. Our finding that the RNF8 E3 ligase has a role in recruiting FANCD2 and PALB2 also provides support for the hypothesis that the two branches of the FA-BRCA pathway are coordinated by ubiquitin signaling. Interestingly, we find that the RNF8 partner, MDC1, as well as the ubiquitin-binding protein, RAP80, specifically recruit PALB2, while a different ubiquitin-binding protein, FAAP20, functions only in the recruitment of FANCD2. Thus, FANCD2 and PALB2 are not recruited in a single linear pathway, rather we define how their localization is coordinated and integrated by a network of ubiquitin-related proteins. We propose that such regulation may enable upstream and downstream FA proteins to act at distinct steps in the repair of ICLs. PMID- 27277790 TI - Renal denervation: are we at a crossroads? PMID- 27277791 TI - Second-Language Learning Ability Revealed by Resting-State Functional Connectivity. PMID- 27277792 TI - Elucidating a Core Semantic Network in the Brain-Implications for Disorders of Semantic Cognition. PMID- 27277793 TI - Task Encoding across the Multiple Demand Cortex Is Consistent with a Frontoparietal and Cingulo-Opercular Dual Networks Distinction. AB - Multiple-demand (MD) regions of the human brain show coactivation during many different kinds of task performance. Previous work based on resting-state functional magnetic resonance imaging (fMRI) has shown that MD regions may be divided into two closely coupled subnetworks centered around the lateral frontoparietal (FP) and cingulo-opercular cortex. Here, we used on-task fMRI to test whether this division is apparent during the performance of an executive task. Furthermore, we investigated whether there is a difference in the encoding of task between the two subnetworks. Using connectivity methods, we found that activity across the entire MD cortex is correlated during task performance. Meanwhile, however, there was significantly stronger connectivity within each of the subnetworks than between them. Using multivoxel pattern analysis, we also found that, although we were able to decode task-relevant information from all regions of the MD cortex, classification accuracy scores were significantly higher in the FP subnetwork. These results suggest a nested picture with MD regions as a whole showing coactivation and broad rule representation, but with significant functional distinctions between component subnetworks. SIGNIFICANCE STATEMENT: Multiple-demand (MD) regions of frontal and parietal cortex appear essential for the orchestration of goal-directed behavior and problem solving. Understanding the relative specialization of regions within the MD cortex is crucial to understanding how we can coordinate and execute complex action plans. By examining functional connectivity during task performance, we extend previous findings suggesting that the MD cortex can be divided into two subnetworks centered around the frontoparietal (FP) and cingulo-opercular (CO) cortex. Furthermore, using multivoxel pattern analysis, we show that, compared with the CO subnetwork, the FP subnetwork manifests more differentiated coding of specific task events. PMID- 27277794 TI - Testosterone during Puberty Shifts Emotional Control from Pulvinar to Anterior Prefrontal Cortex. AB - Increased limbic and striatal activation in adolescence has been attributed to a relative delay in the maturation of prefrontal areas, resulting in the increase of impulsive reward-seeking behaviors that are often observed during puberty. However, it remains unclear whether and how this general developmental pattern applies to the control of social emotional actions, a fundamental adult skill refined during adolescence. This domain of control pertains to decisions involving emotional responses. When faced with a social emotional challenge (e.g., an angry face), we can follow automatic response tendencies and avoid the challenge or exert control over those tendencies by selecting an alternative action. Using an fMRI-adapted social approach-avoidance task, this study identifies how the neural regulation of emotional action control changes as a function of human pubertal development in 14-year-old adolescents (n = 47). Pubertal maturation, indexed by testosterone levels, shifted neural regulation of emotional actions from the pulvinar nucleus of the thalamus and the amygdala to the anterior prefrontal cortex (aPFC). Adolescents with more advanced pubertal maturation showed greater aPFC activity when controlling their emotional action tendencies, reproducing the same pattern consistently observed in adults. In contrast, adolescents of the same age, but with less advanced pubertal maturation, showed greater pulvinar and amygdala activity when exerting similarly effective emotional control. These findings qualify how, in the domain of social emotional actions, executive control shifts from subcortical to prefrontal structures during pubertal development. The pulvinar and the amygdala are suggested as the ontogenetic precursors of the mature control system centered on the anterior prefrontal cortex. SIGNIFICANCE STATEMENT: Adolescents can show distinct behavioral problems when emotionally aroused. This could be related to later development of frontal regions compared with deeper brain structures. This study found that when the control of emotional actions needs to be exerted, more mature adolescents, similar to adults, recruit the anterior prefrontal cortex (aPFC). Less mature adolescents recruit specific subcortical regions, namely the pulvinar and amygdala. These findings identify the subcortical pulvino-amygdalar pathway as a relevant precursor of a mature aPFC emotional control system, opening the way for a neurobiological understanding of how emotion control related disorders emerge during puberty. PMID- 27277795 TI - Experimental Cortical Spreading Depression Induces NMDA Receptor Dependent Potassium Currents in Microglia. AB - Cortical spreading depression (CSD) is a propagating event of neuronal depolarization, which is considered as the cellular correlate of the migraine aura. It is characterized by a change in the intrinsic optical signal and by a negative DC potential shift. Microglia are the resident macrophages of the CNS and act as sensors for pathological changes. In the present study, we analyzed whether microglial cells might sense CSD by recording membrane currents from microglia in acutely isolated cortical mouse brain slices during an experimentally induced CSD. Coincident with the change in the intrinsic optical signal and the negative DC potential shift we recorded an increase in potassium conductance predominantly mediated by K(+) inward rectifier (Kir)2.1, which was blocked by the NMDA receptor antagonist D-AP5. Application of NMDA and an increase in extracellular K(+) mimics the CSD-induced Kir activation. Application of D-AP5, but not the purinergic receptor antagonist RB2, blocks the NMDA-induced Kir activation. The K(+) channel blocker Ba(2+) blocks both the CSD- and the NMDA triggered increase in Kir channel activity. In addition, we could confirm previous findings that microglia in the adult brain do not express functional NMDA receptors by recording from microglia cultured from adult brain. From these observations we conclude that CSD activates neuronal NMDA receptors, which lead to an increase in extracellular [K(+)] resulting in the activation of Kir channel activity in microglia. SIGNIFICANCE STATEMENT: Cortical spreading depression (CSD) is a wave of neuronal depolarization spreading through the cortex and is associated with the aura of migraine. Here we show that microglial cells, which are viewed as pathologic sensors of the brain, can sense this wave. The increase in the extracellular potassium concentration associated with that wave leads to the activation of an inward rectifying potassium conductance in microglia. The involvement of neuronal NMDA receptors is crucial because NMDA mimics that response and microglia do not express functional NMDA receptors. Although it is now evident that CSD leads to a signal in microglia, the consequences of this microglial activation during CSD needs to be explored. PMID- 27277797 TI - Serial Dependence in Perceptual Decisions Is Reflected in Activity Patterns in Primary Visual Cortex. AB - Sensory signals are highly structured in both space and time. These regularities allow expectations about future stimulation to be formed, thereby facilitating decisions about upcoming visual features and objects. One such regularity is that the world is generally stable over short time scales. This feature of the world is exploited by the brain, leading to a bias in perception called serial dependence: previously seen stimuli bias the perception of subsequent stimuli, making them appear more similar to previous input than they really are. What are the neural processes that may underlie this bias in perceptual choice? Does serial dependence arise only in higher-level areas involved in perceptual decision-making, or does such a bias occur at the earliest levels of sensory processing? In this study, human subjects made decisions about the orientation of grating stimuli presented in the left or right visual field while activity patterns in their visual cortex were recorded using fMRI. In line with previous behavioral reports, reported orientation on the current trial was consistently biased toward the previously reported orientation. We found that the orientation signal in V1 was similarly biased toward the orientation presented on the previous trial. Both the perceptual decision and neural effects were spatially specific, such that the perceptual decision and neural representations on the current trial were only influenced by previous stimuli at the same location. These results suggest that biases in perceptual decisions induced by previous stimuli may result from neural biases in sensory cortex induced by recent perceptual history. SIGNIFICANCE STATEMENT: We perceive a stable visual scene, although our visual input is constantly changing. This experience may in part be driven by a bias in visual perception that causes images to be perceived as similar to those previously seen. Here, we provide evidence for a sensory bias that may underlie this perceptual effect. We find that neural representations in early visual cortex are biased toward previous perceptual decisions. Our results suggest a direct neural correlate of serial dependencies in visual perception. These findings elucidate how our perceptual decisions are shaped by our perceptual history. PMID- 27277798 TI - ZIP It: Neural Silencing Is an Additional Effect of the PKM-Zeta Inhibitor Zeta Inhibitory Peptide. AB - Protein kinase M zeta (PKMzeta), an atypical isoform of protein kinase C, has been suggested to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long-term memory (LTM). This evidence is heavily based on the use of zeta inhibitory peptide (ZIP), a supposed specific inhibitor of PKMzeta that interferes with both LTP and LTM. Problematically, both LTP and LTM are unaffected in both constitutive and conditional PKMzeta knock-out mice, yet both are still impaired by ZIP application, suggesting a nonspecific mechanism of action. Because translational interference can disrupt neural activity, we assessed network activity after a unilateral intrahippocampal infusion of ZIP in anesthetized rats. ZIP profoundly reduced spontaneous hippocampal local field potentials, comparable in magnitude to infusions of lidocaine, but with a slower onset and longer duration. Our results highlight a serious confound in interpreting the behavioral effects of ZIP. We suggest that future molecular approaches in neuroscience consider the intervening level of cellular and systems neurophysiology before claiming influences on behavior. SIGNIFICANCE STATEMENT: Long-term memory in the brain is thought to arise from a sustained molecular process that can maintain changes in synaptic plasticity. A so-called candidate for the title of "the memory molecule" is protein kinase M zeta (PKMzeta), mainly because its inhibition by zeta inhibitory peptide (ZIP) interferes with previously established synaptic plasticity and memory. We show that brain applications of ZIP that can impair memory actually profoundly suppress spontaneous brain activity directly or can cause abnormal seizure activity. We suggest that normal brain activity occurring after learning may be a more primary element of memory permanence. PMID- 27277796 TI - Cross-Modal Plasticity in Higher-Order Auditory Cortex of Congenitally Deaf Cats Does Not Limit Auditory Responsiveness to Cochlear Implants. AB - Congenital sensory deprivation can lead to reorganization of the deprived cortical regions by another sensory system. Such cross-modal reorganization may either compete with or complement the "original" inputs to the deprived area after sensory restoration and can thus be either adverse or beneficial for sensory restoration. In congenital deafness, a previous inactivation study documented that supranormal visual behavior was mediated by higher-order auditory fields in congenitally deaf cats (CDCs). However, both the auditory responsiveness of "deaf" higher-order fields and interactions between the reorganized and the original sensory input remain unknown. Here, we studied a higher-order auditory field responsible for the supranormal visual function in CDCs, the auditory dorsal zone (DZ). Hearing cats and visual cortical areas served as a control. Using mapping with microelectrode arrays, we demonstrate spatially scattered visual (cross-modal) responsiveness in the DZ, but show that this did not interfere substantially with robust auditory responsiveness elicited through cochlear implants. Visually responsive and auditory-responsive neurons in the deaf auditory cortex formed two distinct populations that did not show bimodal interactions. Therefore, cross-modal plasticity in the deaf higher-order auditory cortex had limited effects on auditory inputs. The moderate number of scattered cross-modally responsive neurons could be the consequence of exuberant connections formed during development that were not pruned postnatally in deaf cats. Although juvenile brain circuits are modified extensively by experience, the main driving input to the cross-modally (visually) reorganized higher-order auditory cortex remained auditory in congenital deafness. SIGNIFICANCE STATEMENT: In a common view, the "unused" auditory cortex of deaf individuals is reorganized to a compensatory sensory function during development. According to this view, cross-modal plasticity takes over the unused cortex and reassigns it to the remaining senses. Therefore, cross-modal plasticity might conflict with restoration of auditory function with cochlear implants. It is unclear whether the cross-modally reorganized auditory areas lose auditory responsiveness. We show that the presence of cross-modal plasticity in a higher-order auditory area does not reduce auditory responsiveness of that area. Visual reorganization was moderate, spatially scattered and there were no interactions between cross modally reorganized visual and auditory inputs. These results indicate that cross modal reorganization is less detrimental for neurosensory restoration than previously thought. PMID- 27277799 TI - BDNF Signaling Promotes Vestibular Compensation by Increasing Neurogenesis and Remodeling the Expression of Potassium-Chloride Cotransporter KCC2 and GABAA Receptor in the Vestibular Nuclei. AB - Reactive cell proliferation occurs rapidly in the cat vestibular nuclei (VN) after unilateral vestibular neurectomy (UVN) and has been reported to facilitate the recovery of posturo-locomotor functions. Interestingly, whereas animals experience impairments for several weeks, extraordinary plasticity mechanisms take place in the local microenvironment of the VN: newborn cells survive and acquire different phenotypes, such as microglia, astrocytes, or GABAergic neurons, whereas animals eventually recover completely from their lesion-induced deficits. Because brain-derived neurotrophic factor (BDNF) can modulate vestibular functional recovery and neurogenesis in mammals, in this study, we examined the effect of BDNF chronic intracerebroventricular infusion versus K252a (a Trk receptor antagonist) in our UVN model. Results showed that long-term intracerebroventricular infusion of BDNF accelerated the restoration of vestibular functions and significantly increased UVN-induced neurogenesis, whereas K252a blocked that effect and drastically delayed and prevented the complete restoration of vestibular functions. Further, because the level of excitability in the deafferented VN is correlated with behavioral recovery, we examined the state of neuronal excitability using two specific markers: the cation-chloride cotransporter KCC2 (which determines the hyperpolarizing action of GABA) and GABAA receptors. We report for the first time that, during an early time window after UVN, significant BDNF-dependent remodeling of excitability markers occurs in the brainstem. These data suggest that GABA acquires a transient depolarizing action during recovery from UVN, which potentiates the observed reactive neurogenesis and accelerates vestibular functional recovery. These findings suggest that BDNF and/or KCC2 could represent novel treatment strategies for vestibular pathologies. SIGNIFICANCE STATEMENT: In this study, we report for the first time that brain-derived neurotrophic factor potentiates vestibular neurogenesis and significantly accelerates functional recovery after unilateral vestibular injury. We also show that specific markers of excitability, the potassium-chloride cotransporter KCC2 and GABAA receptors, undergo remarkable fluctuations within vestibular nuclei (VN), strongly suggesting that GABA acquires a transient depolarizing action in the VN during the recovery period. This novel plasticity mechanism could explain in part how the system returns to electrophysiological homeostasis between the deafferented and intact VN, considered in the literature to be a key parameter of vestibular compensation. In this context, our results open new perspectives for the development of therapeutic approaches to alleviate the vestibular symptoms and favor vestibular function recovery. PMID- 27277800 TI - beta1-C121W Is Down But Not Out: Epilepsy-Associated Scn1b-C121W Results in a Deleterious Gain-of-Function. AB - Voltage-gated sodium channel (VGSC) beta subunits signal through multiple pathways on multiple time scales. In addition to modulating sodium and potassium currents, beta subunits play nonconducting roles as cell adhesion molecules, which allow them to function in cell-cell communication, neuronal migration, neurite outgrowth, neuronal pathfinding, and axonal fasciculation. Mutations in SCN1B, encoding VGSC beta1 and beta1B, are associated with epilepsy. Autosomal dominant SCN1B-C121W, the first epilepsy-associated VGSC mutation identified, results in genetic epilepsy with febrile seizures plus (GEFS+). This mutation has been shown to disrupt both the sodium-current-modulatory and cell-adhesive functions of beta1 subunits expressed in heterologous systems. The goal of this study was to compare mice heterozygous for Scn1b-C121W (Scn1b(+/W)) with mice heterozygous for the Scn1b-null allele (Scn1b(+/-)) to determine whether the C121W mutation results in loss-of-function in vivo We found that Scn1b(+/W) mice were more susceptible than Scn1b(+/-) and Scn1b(+/+) mice to hyperthermia-induced convulsions, a model of pediatric febrile seizures. beta1-C121W subunits are expressed at the neuronal cell surface in vivo However, despite this, beta1-C121W polypeptides are incompletely glycosylated and do not associate with VGSC alpha subunits in the brain. beta1-C121W subcellular localization is restricted to neuronal cell bodies and is not detected at axon initial segments in the cortex or cerebellum or at optic nerve nodes of Ranvier of Scn1b(W/W) mice. These data, together with our previous results showing that beta1-C121W cannot participate in trans-homophilic cell adhesion, lead to the hypothesis that SCN1B-C121W confers a deleterious gain-of-function in human GEFS+ patients. SIGNIFICANCE STATEMENT: The mechanisms underlying genetic epilepsy syndromes are poorly understood. Closing this gap in knowledge is essential to the development of new medicines to treat epilepsy. We have used mouse models to understand the mechanism of a mutation in the sodium channel gene SCN1B linked to genetic epilepsy with febrile seizures plus. We report that sodium channel beta1 subunit proteins encoded by this mutant gene are expressed at the surface of neuronal cell bodies; however, they do not associate with the ion channel complex nor are they transported to areas of the axon that are critical for proper neuronal firing. We conclude that this disease causing mutation is not simply a loss-of-function, but instead results in a deleterious gain-of-function in the brain. PMID- 27277801 TI - Variability and Correlations in Primary Visual Cortical Neurons Driven by Fixational Eye Movements. AB - The ability to distinguish between elements of a sensory neuron's activity that are stimulus independent versus driven by the stimulus is critical for addressing many questions in systems neuroscience. This is typically accomplished by measuring neural responses to repeated presentations of identical stimuli and identifying the trial-variable components of the response as noise. In awake primates, however, small "fixational" eye movements (FEMs) introduce uncontrolled trial-to-trial differences in the visual stimulus itself, potentially confounding this distinction. Here, we describe novel analytical methods that directly quantify the stimulus-driven and stimulus-independent components of visual neuron responses in the presence of FEMs. We apply this approach, combined with precise model-based eye tracking, to recordings from primary visual cortex (V1), finding that standard approaches that ignore FEMs typically miss more than half of the stimulus-driven neural response variance, creating substantial biases in measures of response reliability. We show that these effects are likely not isolated to the particular experimental conditions used here, such as the choice of visual stimulus or spike measurement time window, and thus will be a more general problem for V1 recordings in awake primates. We also demonstrate that measurements of the stimulus-driven and stimulus-independent correlations among pairs of V1 neurons can be greatly biased by FEMs. These results thus illustrate the potentially dramatic impact of FEMs on measures of signal and noise in visual neuron activity and also demonstrate a novel approach for controlling for these eye-movement-induced effects. SIGNIFICANCE STATEMENT: Distinguishing between the signal and noise in a sensory neuron's activity is typically accomplished by measuring neural responses to repeated presentations of an identical stimulus. For recordings from the visual cortex of awake animals, small "fixational" eye movements (FEMs) inevitably introduce trial-to-trial variability in the visual stimulus, potentially confounding such measures. Here, we show that FEMs often have a dramatic impact on several important measures of response variability for neurons in primary visual cortex. We also present an analytical approach for quantifying signal and noise in visual neuron activity in the presence of FEMs. These results thus highlight the importance of controlling for FEMs in studies of visual neuron function, and demonstrate novel methods for doing so. PMID- 27277802 TI - Cholinergic Interneurons Use Orbitofrontal Input to Track Beliefs about Current State. AB - When conditions change, organisms need to learn about the changed conditions without interfering with what they already know. To do so, they can assign the new learning to a new "state" and the old learning to a previous state. This state assignment is fundamental to behavioral flexibility. Cholinergic interneurons (CINs) in the dorsomedial striatum (DMS) are necessary for associative information to be compartmentalized in this way, but the mechanism by which they do so is unknown. Here we addressed this question by recording putative CINs from the DMS in rats performing a task consisting of a series of trial blocks, or states, that required the recall and application of contradictory associative information. We found that individual CINs in the DMS represented the current state throughout each trial. These state correlates were not observed in dorsolateral striatal CINs recorded in the same rats. Notably, DMS CIN ensembles tracked rats' beliefs about the current state such that, when states were miscoded, rats tended to make suboptimal choices reflecting the miscoding. State information held by the DMS CINs also depended completely on the orbitofrontal cortex, an area that has been proposed to signal environmental states. These results suggest that CINs set the stage for recalling associative information relevant to the current environment by maintaining a real-time representation of the current state. Such a role has novel implications for understanding the neural basis of a variety of psychiatric diseases, such as addiction or anxiety disorders, in which patients generalize inappropriately (or fail to generalize) between different environments. SIGNIFICANCE STATEMENT: Striatal cholinergic interneurons (CINs) are thought to be identical to tonically active neurons. These neurons have long been thought to have an important influence on striatal processing during reward-related learning. Recently, a more specific function for striatal CINs has been suggested, which is that they are necessary for striatal learning to be compartmentalized into different states as the state of the environment changes. Here we report that putative CINs appear to track rats' beliefs about which environmental state is current. We further show that this property of CINs depends on orbitofrontal cortex input and is correlated with choices made by rats. These findings could provide new insight into neuropsychiatric diseases that involve improper generalization between different contexts. PMID- 27277804 TI - Olfactory Ensheathing Cell Transplantation after a Complete Spinal Cord Transection Mediates Neuroprotective and Immunomodulatory Mechanisms to Facilitate Regeneration. AB - Multiple neural and peripheral cell types rapidly respond to tissue damage after spinal cord injury to form a structurally and chemically inhibitory scar that limits axon regeneration. Astrocytes form an astroglial scar and produce chondroitin sulfate proteoglycans (CSPGs), activate microglia, and recruit blood derived immune cells to the lesion for debris removal. One beneficial therapy, olfactory ensheathing cell (OEC) transplantation, results in functional improvements and promotes axon regeneration after spinal cord injury. The lack of an OEC-specific marker, however, has limited the investigation of mechanisms underlying their proregenerative effects. We compared the effects of enhanced green fluorescent protein-labeled fibroblast (FB) and OEC transplants acutely after a complete low-thoracic spinal cord transection in adult rats. We assessed the preservation of neurons and serotonergic axons, the levels of inhibitory CSPGs and myelin debris, and the extent of immune cell activation between 1 and 8 weeks postinjury. Our findings indicate that OECs survive longer than FBs post transplantation, preserve axons and neurons, and reduce inhibitory molecules in the lesion core. Additionally, we show that OECs limit immune-cell activation and infiltration, whereas FBs alter astroglial scar formation and increase immune cell infiltration and concomitant secondary tissue damage. Administration of cyclosporine-A to enhance graft survival demonstrated that immune suppression can augment OEC contact-mediated protection of axons and neurons during the first 2 weeks postinjury. Collectively, these data suggest that OECs have neuroprotective and immunomodulatory mechanisms that create a supportive environment for neuronal survival and axon regeneration after spinal cord injury. SIGNIFICANCE STATEMENT: Spinal cord injury creates physical and chemical barriers to axon regeneration. We used a complete spinal cord transection model and olfactory ensheathing cell (OEC) or fibroblast (FB; control) transplantation as a repair strategy. OECs, but not FBs, intermingled with astrocytes, facilitated astroglial scar border formation and sequestered invading peripheral cells. OECs attenuated immune cell infiltration, reduced secondary tissue damage, protected neurons and axons in the lesion core, and helped clear myelin debris. Immunosuppression enhanced survival of OECs and FBs, but only OEC transplantation promoted scaffold formation in the lesion site that facilitated axon regeneration and neuron preservation. PMID- 27277803 TI - Quantitative Trait Loci and a Novel Genetic Candidate for Fear Learning. AB - Trauma- and stress-related disorders are clinically heterogeneous and associated with substantial genetic risk. Understanding the biological origins of heterogeneity of key intermediate phenotypes such as cognition and emotion can provide novel mechanistic insights into disorder pathogenesis. Performing quantitative genetics in animal models is a tractable strategy for examining both the genetic basis of intermediate phenotypes and functional testing of candidate quantitative traits genes (QTGs). Here, existing and newly collected data were used for collaborative genome-wide mapping of cued fear acquisition and expression in 65 mouse strains from the BXD genetic reference panel. For fear acquisition, we identified a significant locus on chromosome (Chr) 10 and eight suggestive loci on Chr 2, 4, 5, 11, 13, and 15. For fear expression, we identified one significant and another highly suggestive locus on Chr 13, as well as four suggestive loci on Chr 10, 11, and X. Across these loci, 60 putative QTGs were identified. The quantitative trait locus on distal Chr 13 contained a single, highly promising gene at the location of the peak likelihood ratio statistic score. The gene, hyperpolarization-activated cyclic nucleotide-gated channel 1 (Hcn1), regulates neuronal excitability. Validation experiments using behavioral pharmacology revealed that functional Hcn channels in the basolateral amygdala are necessary for conditioned fear acquisition and expression. Hcn1, together with the other candidate QTGs, thus provide new targets for neurobiological and treatment studies of fear learning and trauma- and stress related disorders. SIGNIFICANCE STATEMENT: There is a knowledge gap in understanding the genetic contributions to behavioral heterogeneity in typical and atypical populations. Mouse genetic reference panels (GRPs) provide one approach for identifying genetic sources of variation. Here, we identified three loci for conditioned fear acquisition and expression in a mouse GRP. Each locus contained candidate quantitative trait genes (QTGs). One locus had a single QTG, Hcn1 (hyperpolarization-activated cyclic nucleotide-gated channel 1), which has been implicated in neuronal excitability and learning. This discovery was validated using behavioral pharmacology, revealing that Hcn channels in the basolateral amygdala are required for fear acquisition and expression. The study thus identifies novel candidate QTGs that may contribute to variation in emotional learning and highlight the utility of mouse GRPs for the identification of genes underlying complex traits. PMID- 27277805 TI - Cholinergic Regulation of hnRNPA2/B1 Translation by M1 Muscarinic Receptors. AB - Cholinergic vulnerability, characterized by loss of acetylcholine (ACh), is one of the hallmarks of Alzheimer's disease (AD). Previous work has suggested that decreased ACh activity in AD may contribute to pathological changes through global alterations in alternative splicing. This occurs, at least partially, via the regulation of the expression of a critical protein family in RNA processing, heterogeneous nuclear ribonucleoprotein (hnRNP) A/B proteins. These proteins regulate several steps of RNA metabolism, including alternative splicing, RNA trafficking, miRNA export, and gene expression, providing multilevel surveillance in RNA functions. To investigate the mechanism by which cholinergic tone regulates hnRNPA2/B1 expression, we used a combination of genetic mouse models and in vivo and in vitro techniques. Decreasing cholinergic tone reduced levels of hnRNPA2/B1, whereas increasing cholinergic signaling in vivo increased expression of hnRNPA2/B1. This effect was not due to decreased hnRNPA2/B1 mRNA expression, increased aggregation, or degradation of the protein, but rather to decreased mRNA translation by nonsense-mediated decay regulation of translation. Cell culture and knock-out mice experiments demonstrated that M1 muscarinic signaling is critical for cholinergic control of hnRNPA2/B1 protein levels. Our experiments suggest an intricate regulation of hnRNPA2/B1 levels by cholinergic activity that interferes with alternative splicing in targeted neurons mimicking deficits found in AD. SIGNIFICANCE STATEMENT: In Alzheimer's disease, degeneration of basal forebrain cholinergic neurons is an early event. These neurons communicate with target cells and regulate their long-term activity by poorly understood mechanisms. Recently, the splicing factor hnRNPA2/B, which is decreased in Alzheimer's disease, was implicated as a potential mediator of long term cholinergic regulation. Here, we demonstrate a mechanism by which cholinergic signaling controls the translation of hnRNPA2/B1 mRNA by activation of M1 muscarinic type receptors. Loss of cholinergic activity can have profound effects in target cells by modulating hnRNPA2/B1 levels. PMID- 27277806 TI - Intracranial Recordings of Occipital Cortex Responses to Illusory Visual Events. AB - Ambiguous visual stimuli elicit different perceptual interpretations over time, creating the illusion that a constant stimulus is changing. We investigate whether such spontaneous changes in visual perception involve occipital brain regions specialized for processing visual information, despite the absence of concomitant changes in stimulation. Spontaneous perceptual changes observed while viewing a binocular rivalry stimulus or an ambiguous structure-from-motion stimulus were compared with stimulus-induced perceptual changes that occurred in response to an actual stimulus change. Intracranial recordings from human occipital cortex revealed that spontaneous and stimulus-induced perceptual changes were both associated with an early transient increase in high-frequency power that was more spatially confined than a later transient decrease in low frequency power. We suggest that the observed high-frequency and low-frequency modulations relate to initiation and maintenance of a percept, respectively. Our results are compatible with the idea that spontaneous changes in perception originate from competitive interactions within visual neural networks. SIGNIFICANCE STATEMENT: Ambiguous visual stimuli elicit different perceptual interpretations over time, creating the illusion that a constant stimulus is changing. The literature on the neural correlates of conscious visual perception remains inconclusive regarding the extent to which such spontaneous changes in perception involve sensory brain regions. In an attempt to bridge the gap between existing animal and human studies, we recorded from intracranial electrodes placed on the human occipital lobe. We compared two different kinds of ambiguous stimuli, binocular rivalry and the phenomenon of ambiguous structure-from-motion, enabling generalization of our findings across different stimuli. Our results indicate that spontaneous and stimulus-induced changes in perception (i.e., "illusory" and "real" changes in the stimulus, respectively) may involve sensory regions to a similar extent. PMID- 27277807 TI - Perineuronal Nets Suppress Plasticity of Excitatory Synapses on CA2 Pyramidal Neurons. AB - Long-term potentiation of excitatory synapses on pyramidal neurons in the stratum radiatum rarely occurs in hippocampal area CA2. Here, we present evidence that perineuronal nets (PNNs), a specialized extracellular matrix typically localized around inhibitory neurons, also surround mouse CA2 pyramidal neurons and envelop their excitatory synapses. CA2 pyramidal neurons express mRNA transcripts for the major PNN component aggrecan, identifying these neurons as a novel source for PNNs in the hippocampus. We also found that disruption of PNNs allows synaptic potentiation of normally plasticity-resistant excitatory CA2 synapses; thus, PNNs play a role in restricting synaptic plasticity in area CA2. Finally, we found that postnatal development of PNNs on CA2 pyramidal neurons is modified by early life enrichment, suggesting that the development of circuits containing CA2 excitatory synapses are sensitive to manipulations of the rearing environment. SIGNIFICANCE STATEMENT: Perineuronal nets (PNNs) are thought to play a major role in restricting synaptic plasticity during postnatal development, and are altered in several models of neurodevelopmental disorders, such as schizophrenia and Rett syndrome. Although PNNs have been predominantly studied in association with inhibitory neurons throughout the brain, we describe a dense expression of PNNs around excitatory pyramidal neurons in hippocampal area CA2. We also provide insight into a previously unrecognized role for PNNs in restricting plasticity at excitatory synapses and raise the possibility of an early critical period of hippocampal plasticity that may ultimately reveal a key mechanism underlying learning and memory impairments of PNN-associated neurodevelopmental disorders. PMID- 27277808 TI - mir-500-Mediated GAD67 Downregulation Contributes to Neuropathic Pain. AB - Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the interactions between synaptic dysfunction and the genes that are involved in persistent pain remain elusive. In the present study, we found that neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection significantly impaired the function of GABAergic synapses of spinal dorsal horn neurons via the reduction of the GAD67 expression. We also found that mir-500 expression was significantly increased and involved in the modulation of GAD67 expression via targeting the specific site of Gad1 gene in the dorsal horn. In addition, knock-out of mir-500 or using mir-500 antagomir rescued the GABAergic synapses in the spinal dorsal horn neurons and attenuated the sensitized pain behavior in the rats with neuropathic pain. To our knowledge, this is the first study to investigate the function significance and the underlying molecular mechanisms of mir-500 in the process of neuropathic pain, which sheds light on the development of novel therapeutic options for neuropathic pain. SIGNIFICANCE STATEMENT: Neuropathic pain is a common neurobiological disease involving multifaceted maladaptations ranging from gene modulation to synaptic dysfunction, but the underlying molecular mechanisms remain elusive. The present study illustrates for the first time a mir-500-mediated mechanism underlying spinal GABAergic dysfunction and sensitized pain behavior in neuropathic pain induced by the chemotherapeutic drug paclitaxel or L5 ventral root transection, which sheds light on the development of novel therapeutic options for neuropathic pain. PMID- 27277813 TI - Hyperspectral backscatter imaging: a label-free approach to cytogenetics. AB - Current techniques for chromosome analysis need to be improved for rapid, economical identification of complex chromosomal defects by sensitive and selective visualisation. In this paper, we present a straightforward method for characterising unstained human metaphase chromosomes. Backscatter imaging in a dark-field setup combined with visible and short near-infrared spectroscopy is used to monitor morphological differences in the distribution of the chromosomal fine structure in human metaphase chromosomes. The reasons for the scattering centres in the fine structure are explained. Changes in the scattering centres during preparation of the metaphases are discussed. FDTD simulations are presented to substantiate the experimental findings. We show that local scattering features consisting of underlying spectral modulations of higher frequencies associated with a high variety of densely packed chromatin can be represented by their scatter profiles even on a sub-microscopic level. The result is independent of the chromosome preparation and structure size. This analytical method constitutes a rapid, cost-effective and label-free cytogenetic technique which can be used in a standard light microscope. Graphical abstract Hyperspectral backscatter imaging for label-free characterization. PMID- 27277809 TI - Distinct Nrf2 Signaling Mechanisms of Fumaric Acid Esters and Their Role in Neuroprotection against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Experimental Parkinson's-Like Disease. AB - A promising approach to neurotherapeutics involves activating the nuclear-factor E2-related factor 2 (Nrf2)/antioxidant response element signaling, which regulates expression of antioxidant, anti-inflammatory, and cytoprotective genes. Tecfidera, a putative Nrf2 activator, is an oral formulation of dimethylfumarate (DMF) used to treat multiple sclerosis. We compared the effects of DMF and its bioactive metabolite monomethylfumarate (MMF) on Nrf2 signaling and their ability to block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinson's disease (PD). We show that in vitro DMF and MMF activate the Nrf2 pathway via S-alkylation of the Nrf2 inhibitor Keap1 and by causing nuclear exit of the Nrf2 repressor Bach1. Nrf2 activation by DMF but not MMF was associated with depletion of glutathione, decreased cell viability, and inhibition of mitochondrial oxygen consumption and glycolysis rates in a dose-dependent manner, whereas MMF increased these activities in vitro However, both DMF and MMF upregulated mitochondrial biogenesis in vitro in an Nrf2-dependent manner. Despite the in vitro differences, both DMF and MMF exerted similar neuroprotective effects and blocked MPTP neurotoxicity in wild-type but not in Nrf2 null mice. Our data suggest that DMF and MMF exhibit neuroprotective effects against MPTP neurotoxicity because of their distinct Nrf2-mediated antioxidant, anti-inflammatory, and mitochondrial functional/biogenetic effects, but MMF does so without depleting glutathione and inhibiting mitochondrial and glycolytic functions. Given that oxidative damage, neuroinflammation, and mitochondrial dysfunction are all implicated in PD pathogenesis, our results provide preclinical evidence for the development of MMF rather than DMF as a novel PD therapeutic. SIGNIFICANCE STATEMENT: Almost two centuries since its first description by James Parkinson, Parkinson's disease (PD) remains an incurable disease with limited symptomatic treatment. The current study provides preclinical evidence that a Food and Drug Administration-approved drug, dimethylfumarate (DMF), and its metabolite monomethylfumarate (MMF) can block nigrostriatal dopaminergic neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine mouse model of PD. We elucidated mechanisms by which DMF and its active metabolite MMF activates the redox-sensitive transcription factor nuclear-factor-E2-related factor 2 (Nrf2) to upregulate antioxidant, anti inflammatory, mitochondrial biosynthetic and cytoprotective genes to render neuroprotection via distinct S-alkylating properties and depletion of glutathione. Our data suggest that targeting Nrf2-mediated gene transcription using MMF rather than DMF is a promising approach to block oxidative stress, neuroinflammation, and mitochondrial dysfunction for therapeutic intervention in PD while minimizing side effects. PMID- 27277811 TI - A sensitive electrochemical impedance immunosensor for determination of malachite green and leucomalachite green in the aqueous environment. AB - Application of malachite green (MG) and leucomalachite green (LMG) in fish farm water causes an environmental problem. This study proposes for the first time a sensitive and convenient electrochemical impedance spectroscopy (EIS) method for determining MG and LMG by a bovine serum albumin-decorated gold nanocluster (BSA AuNC)/antibody composite film-based immunosensor. In order to improve the analytical performance, the glassy carbon electrode (GCE) was modified with 1, 4 phenylenediamine to form a stable layer, and then, BSA-AuNCs were covalently bound to the GCE. An adequate quantity of the polyclonal antibody of LMG was immobilized onto the surface of the BSA-AuNCs by the chemical reaction of EDC/NHS. The sensors can respond to the specific target based on specific covalent bonding. The experimental parameters, such as the pH, incubating concentration, and time, have been investigated and optimized. The calibration curve for LMG was linear in the range of 0.1~10.0 ng/mL with the limit of detection (LOD) 0.03 ng/mL. Furthermore, the sum of MG and LMG was detected in fish farm water by MG reduction. The recovery was between 89.7 % and 99.2 % in spiked samples. The EC sensor method was also compared with the ELISA method and validated by the LC-MS/MS method, which proves its great promise as a field instrument for the rapid monitoring of MG and LMG pollution. Graphical abstract 1, 4-Phenylenediamine and BSA-AuNC/antibody-decorated glassy carbon electrodes have been used for the impedimetric detection of the sum of malachite green and leucomalachite green via specific immuno-binding. PMID- 27277810 TI - TLR4 Deficiency Impairs Oligodendrocyte Formation in the Injured Spinal Cord. AB - Acute oligodendrocyte (OL) death after traumatic spinal cord injury (SCI) is followed by robust neuron-glial antigen 2 (NG2)-positive OL progenitor proliferation and differentiation into new OLs. Inflammatory mediators are prevalent during both phases and can influence the fate of NG2 cells and OLs. Specifically, toll-like receptor (TLR) 4 signaling induces OL genesis in the naive spinal cord, and lack of TLR4 signaling impairs white matter sparing and functional recovery after SCI. Therefore, we hypothesized that TLR4 signaling may regulate oligodendrogenesis after SCI. C3H/HeJ (TLR4-deficient) and control (C3H/HeOuJ) mice received a moderate midthoracic spinal contusion. TLR4-deficient mice showed worse functional recovery and reduced OL numbers compared with controls at 24 h after injury through chronic time points. Acute OL loss was accompanied by reduced ferritin expression, which is regulated by TLR4 and needed for effective iron storage. TLR4-deficient injured spinal cords also displayed features consistent with reduced OL genesis, including reduced NG2 expression, fewer BrdU-positive OLs, altered BMP4 signaling and inhibitor of differentiation 4 (ID4) expression, and delayed myelin phagocytosis. Expression of several factors, including IGF-1, FGF2, IL-1beta, and PDGF-A, was altered in TLR4 deficient injured spinal cords compared with wild types. Together, these data show that TLR4 signaling after SCI is important for OL lineage cell sparing and replacement, as well as in regulating cytokine and growth factor expression. These results highlight new roles for TLR4 in endogenous SCI repair and emphasize that altering the function of a single immune-related receptor can dramatically change the reparative responses of multiple cellular constituents in the injured CNS milieu. SIGNIFICANCE STATEMENT: Myelinating cells of the CNS [oligodendrocytes (OLs)] are killed for several weeks after traumatic spinal cord injury (SCI), but they are replaced by resident progenitor cells. How the concurrent inflammatory signaling affects this endogenous reparative response is unclear. Here, we provide evidence that immune receptor toll-like receptor 4 (TLR4) supports OL lineage cell sparing, long-term OL and OL progenitor replacement, and chronic functional recovery. We show that TLR4 signaling is essential for acute iron storage, regulating cytokine and growth factor expression, and efficient myelin debris clearance, all of which influence OL replacement. Importantly, the current study reveals that a single immune receptor is essential for repair responses after SCI, and the potential mechanisms of this beneficial effect likely change over time after injury. PMID- 27277814 TI - Lectin binding studies on a glycopolymer brush flow-through biosensor by localized surface plasmon resonance. AB - A localized surface plasmon resonance biosensor in a flow-through configuration was applied for investigating kinetics of lectin binding to surface-grafted glycopolymer brushes. Polycarbonate filter membranes with pore sizes of 400 nm were coated with a 114-nm thick gold layer and used as substrate for surface initiated atom-transfer radical polymerization of a glycomonomer. These grafted from glycopolymer brushes were further modified with two subsequent enzymatic reactions on the surface to yield an immobilized trisaccharide presenting brush. Specific binding of lectins including Clostridium difficile toxin A receptor domain to the glycopolymer brush surface could be investigated in a microfluidic setup with flow-through of the analytes and transmission surface plasmon resonance spectroscopy. Graphical abstract Glycopolymer brushes serve as high affinity ligands for lectin and toxin interactions in a sensitive, disposable flow-through LSPR biosensor. PMID- 27277815 TI - Monitoring of changes in lipid profiles during PLK1 knockdown in cancer cells using DESI MS. AB - The importance of the polo-like kinase 1 (PLK1) gene is increasing substantially both as a biomarker and as a target for highly specific cancer therapy. This is due to its involvement in multiple points of cell progression and carcinogenesis. PLK1 inhibitors' efficacy in treating human cancers has been limited due to the lack of a specific targeting strategy. Here, we describe a method of targeted downregulation of PLK1 in cancer cells and the concomitant rapid detection of surface lipidomic perturbations using desorption electrospray ionization mass spectrometry (DESI MS). The efficient delivery of siRNA targeting PLK1 gene selectively to the cancer cells is achieved by targeting overexpressed cell surface epithelial cell adhesion molecule (EpCAM) by the EpDT3 aptamer. The chimeric aptamer (EpDT3-siPLK1) showed the knockdown of PLK1 gene expression and PLK1 protein levels by quantitative PCR and western blotting, respectively. The abundant surface lipids, phosphatidylcholines (PCs), such as PC(32:1) (m/z 754.6), PC(34:1) (m/z 782.6), and PC(36:2) (m/z 808.6), were highly expressed in MCF-7 and WERI-RB1 cancer cells compared to normal MIO-M1 cells and they were observed using DESI MS. These overexpressed cell surface lipids in the cancer cells were downregulated upon the treatment of EpDT3-siPLK1 chimera indicating a novel role of PLK1 to regulate surface lipid expression in addition to the efficient selective cancer targeting ability. Our results indicate that DESI MS has a potential ability to rapidly monitor aptamer-mediated cancer therapy and accelerate the drug discovery process. Graphical abstract Binding of aptamer chimera to the cells and changes in lipid profile. PMID- 27277816 TI - Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2. AB - PURPOSE: In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16-20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment. MATERIALS AND METHODS: All sequential treatment naive mRCC patients treated with HDIL-2 at the University of Utah (1988-2013) and University of Michigan (1997-2013) were included. Best responses on treatment were associated with survival outcomes using log-rank and COX regression with a landmark analysis at 2 months. RESULTS: 391 patients (75 % male; median age 55 years) were included and belonged to the following prognostic risk categories: 20 % good, 64 % intermediate, and 15 % poor. Best responses on treatment were complete response (9 %), partial response (10 %), stable disease (32 %), progressive disease (42 %), and not evaluable for response (7 %). No significant differences in progression-free survival (HR 0.74, 95 % CI 0.48-1.1, p = 0.14) or overall survival (HR 0.66, 95 % CI 0.39-1.09, p = 0.11) were observed between patients achieving partial response versus stable disease. Significant differences in progression-free survival (HR 0.13, 95 % CI 0.09-0.22, p < 0.0001) and overall survival (HR 0.33, 95 % CI 0.23-0.48, p < 0.0001) were observed between patients achieving stable disease compared to those with progressive disease and who were not evaluable. CONCLUSIONS: Survival benefit with HDIL-2 is achieved in ~50 % patients and extends beyond those achieving objective responses. PMID- 27277817 TI - Fibre concentrate from artichoke (Cynara scolymus L.) stem by-products: Characterization and application as a bakery product ingredient. AB - The potential of fibre concentrate from artichoke stem by-product in bakery application was investigated. The elaboration of fibre concentrate was characterized by an extraction yield of 48.5%. The chemical composition showed high total dietary fibre (85 g/100 g d.m) and low lipid contents (0.5 g/100 g d.m). The fibre concentrate showed good water holding capacity (8.17 g/g) and high oil holding capacity (16.17 g/g). The effect of fibre concentrate incorporation to wheat dough, at level of 2%, on the rheological properties and physical characteristics of bread was also evaluated. The results showed that the addition of fibre concentrate in wheat flour significantly improved (P < 0.05) dough properties inducing an increase of water absorption, stability and tenacity, and a reduction of extensibility and softening in comparison to the dough without fibre. The colour values of the crust and crumb were significantly (P < 0.05) altered by the addition of fibre concentrate. It was also found that incorporation of fibre concentrate to bread produced a comparable specific volume and enhanced the shelf life, as textural studies revealed. PMID- 27277818 TI - Exploratory Literature Meta-Analysis to Characterize the Relationship Between Early and Longer Term Body Weight Loss for Antiobesity Compounds. AB - The presented analysis was performed to characterize the relationship between treatment-related early (week 4) and longer term (3-6 months) weight loss to understand the potential utility of 4-week proof-of-mechanism studies in the early decision-making process during clinical development of new antiobesity compounds. A regression-based meta-analysis was performed leveraging publically available clinical outcomes data to (1) characterize the within-trial relationship between treatment-related early and longer term body weight loss and (2) identify and quantify key covariate effects on this relationship. Data from 89 randomized clinical trials with 209 treatment arms, representing observations from 54 461 patients and 9 treatments, were available for the meta-analysis. Results indicated that (1) there is a correlation between treatment-related early and longer term body weight loss (r > 0.9), (2) baseline body weight influences the relationship between early and longer term weight loss, whereas comorbidity such as type 2 diabetes mellitus, class of drugs including GLP-1 analogues and the antiobesity compounds lorcaserin or phentermine/topiramate showed no significant effects on this relationship. The model was externally evaluated with data from the investigational compound beloranib, for which longer term weight loss could be successfully predicted based on early response data. Based on these results, the identified strong relationship between treatment-related early and longer term weight loss appears to be independent of mechanism of action. Thus, findings from this analysis can optimize design of clinical studies and facilitate development of new anti-obesity compounds. PMID- 27277820 TI - Staged Delayed Sternal Closure Using a Binder Clip After Pediatric Cardiac Surgery. AB - After pediatric cardiac surgery, patients who undergo delayed sternal closure may become hemodynamically unstable. We performed a staged sternal closure technique using a binder clip in 31 consecutive patients to minimize cardiopulmonary instability. Only one patient (3.2%) died of mediastinitis. Thus, our technique may be safe and minimize cardiopulmonary instability. doi: 10.1111/jocs.12767 (J Card Surg 2016;31:464-466). PMID- 27277821 TI - Dissociation of NSC606985 induces atypical ER-stress and cell death in prostate cancer cells. AB - Castration-resistant prostate cancer (CRPC) is a major cause of prostate cancer (Pca) death. Chemotherapy is able to improve the survival of CRPC patients. We previously found that NSC606985 (NSC), a highly water-soluble camptothecin analog, induced cell death in Pca cells via interaction with topoisomerase 1 and activation of the mitochondrial apoptotic pathway. To further elucidate the role of NSC, we studied the effect of NSC on ER-stress and its association with NSC induced cell death in Pca cells. NSC produced a time- and dose-dependent induction of GRP78, CHOP and XBP1s mRNA, and CHOP protein expression in Pca cells including DU145, indicating an activation of ER-stress. However, unlike conventional ER-stress in which GRP78 protein is increased, NSC produced a time- and dose-dependent U-shape change in GRP78 protein in DU145 cells. The NSC induced decrease in GRP78 protein was blocked by protease inhibitors, N-acetyl-L leucyl-L-leucylnorleucinal (ALLN), a lysosomal protease inhibitor, and epoxomicin (EPO), a ubiquitin-protease inhibitor. ALLN, but not EPO, also partially inhibited NSC-induced cell death. However, both 4-PBA and TUDCA, two chemical chaperons that effectively reduced tunicamycin-induced ER-stress, failed to attenuate NSC-induced GRP78, CHOP and XBP1s mRNA expression and cell death. Moreover, knockdown of NSC induction of CHOP expression using a specific siRNA had no effect on NSC-induced cytochrome c release and NSC-induced cell death. These results suggest that NSC produced an atypical ER-stress that is dissociated from NSC-induced activation of the mitochondrial apoptotic pathway and NSC induced cell death in DU145 prostate cancer cells. PMID- 27277822 TI - [Input of a laboratory in the management of patients with Ebola virus disease and in the training of health personnel: experience of the Forecariah Ebola treatment centre (Guinea) in 2015]. AB - Ebola virus disease (EVD) is associated with a high lethality rate even when the afflicted are provided with good support in an Ebola treatment center (ETC). Basic laboratory tests can help to better understand the pathophysiology of the disease, to guide treatment and to establish simple protocols and procedures tailored to the practice of medicine in the context of such precarious environment for caregivers. Based on a few clinical cases of patients treated in the ETC of Forecariah, Guinea, run by the French Red Cross, this article describes the difficult conditions associated with the provision of medical practice in this challenging environment, aiming to minimize the casualties in the EVD patient and to train the health staff. PMID- 27277823 TI - A molecular imaging biosensor detects in vivo protein folding and misfolding. AB - Aberrant protein folding represents the molecular basis of many important human diseases. Although the discovery of new anti-misfolding drugs is a major priority in molecular therapeutics, there is currently no generalizable protein folding assay for use in cell-based high throughput screening (HTS) of chemical libraries, or for in vivo imaging. We molecularly engineered a bioluminescence based biosensor composed of rationally split Firefly luciferase reporter fragments flanking a test protein, and used this in a protein-fragment complementation assay to quantitatively measure folding of the test protein. We comprehensively validated this biosensor in vitro, in cells, and by optically imaging protein folding and misfolding in living mice using several test proteins including enhanced green fluorescent protein, Renilla luciferase, Gaussia luciferase, and SIRT1. Applications of this novel biosensor are potentially far reaching in both cell-based HTS approaches to discover new anti-misfolding drugs, and when using the same biosensor in validation studies of drug candidates in small animal models. KEY MESSAGES: Novel anti-misfolding drugs are needed as molecular therapeutics for many diseases. We developed first in vivo imaging protein folding biosensor to aid drug discovery. Biosensor created by flanking a test protein with rationally split Firefly luciferase. Biosensor validated by detecting folding of test proteins EGFP, Rluc, Gluc, and SIRT1. Generalizable molecular biosensor for translational applications in drug screening. PMID- 27277825 TI - A retrospective evaluation of lomustine (CeeNU) in 32 treatment naive cats with intermediate to large cell gastrointestinal lymphoma (2006-2013). AB - Multi-drug chemotherapy protocols for feline lymphoma have demonstrated variable efficacy and tolerability. In phase I trials, lomustine has demonstrated efficacy for cats with lymphoma though its use for treatment naive feline intermediate/large cell gastrointestinal (GI) lymphoma remains unknown. This study evaluated the efficacy and tolerability of lomustine for the treatment of feline GI lymphoma. Thirty-two cats with histologically or cytologically confirmed intermediate/large cell GI lymphoma were evaluated retrospectively. Factors assessed included clinical signs, hematologic/biochemical parameters and use of l-asparaginase at induction. A response rate of 50% (16/32), with median duration of response of 302 days (range 64-1450 days), was found. Median progression-free interval was 132 days (range 31-1450 days), with overall median survival time of 108 days (range 4-1488 days). History of hyporexia, presence of anaemia and dose of lomustine were significantly associated with progression-free survival. Overall, lomustine is a well-tolerated and effective treatment for feline GI lymphoma. PMID- 27277824 TI - Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. AB - Apolipoprotein (apo) E was initially described as a lipid transport protein and major ligand for low density lipoprotein (LDL) receptors with a role in cholesterol metabolism and cardiovascular disease. It has since emerged as a major risk factor (causative gene) for Alzheimer's disease and other neurodegenerative disorders. Detailed understanding of the structural features of the three isoforms (apoE2, apoE3, and apoE4), which differ by only a single amino acid interchange, has elucidated their unique functions. ApoE2 and apoE4 increase the risk for heart disease: apoE2 increases atherogenic lipoprotein levels (it binds poorly to LDL receptors), and apoE4 increases LDL levels (it binds preferentially to triglyceride-rich, very low density lipoproteins, leading to downregulation of LDL receptors). ApoE4 also increases the risk for neurodegenerative diseases, decreases their age of onset, or alters their progression. ApoE4 likely causes neurodegeneration secondary to its abnormal structure, caused by an interaction between its carboxyl- and amino-terminal domains, called domain interaction. When neurons are stressed or injured, they synthesize apoE to redistribute cholesterol for neuronal repair or remodeling. However, because of its altered structure, neuronal apoE4 undergoes neuron specific proteolysis, generating neurotoxic fragments (12-29 kDa) that escape the secretory pathway and cause mitochondrial dysfunction and cytoskeletal alterations, including tau phosphorylation. ApoE4-associated pathology can be prevented by small-molecule structure correctors that block domain interaction by converting apoE4 to a molecule that resembles apoE3 both structurally and functionally. Structure correctors are a potential therapeutic approach to reduce apoE4 pathology in both cardiovascular and neurological disorders. PMID- 27277826 TI - Structural identification of electron transfer dissociation products in mass spectrometry using infrared ion spectroscopy. AB - Tandem mass spectrometry occupies a principle place among modern analytical methods and drives many developments in the 'omics' sciences. Electron attachment induced dissociation methods, as alternatives for collision-induced dissociation have profoundly influenced the field of proteomics, enabling among others the top down sequencing of entire proteins and the analysis of post-translational modifications. The technique, however, produces more complex mass spectra and its radical-driven reaction mechanisms remain incompletely understood. Here we demonstrate the facile structural characterization of electron transfer dissociation generated peptide fragments by infrared ion spectroscopy using the tunable free-electron laser FELIX, aiding the elucidation of the underlying dissociation mechanisms. We apply this method to verify and revise previously proposed product ion structures for an often studied model tryptic peptide, [AlaAlaHisAlaArg+2H](2+). Comparing experiment with theory reveals that structures that would be assigned using only theoretical thermodynamic considerations often do not correspond to the experimentally sampled species. PMID- 27277827 TI - Longitudinal strain of left ventricular basal segments and E/e' ratio differentiate primary cardiac amyloidosis at presentation from hypertensive hypertrophy: an automated function imaging study. AB - BACKGROUND: Longitudinal strain is an early marker of left ventricular (LV) dysfunction in several cardiac diseases. Our aim was to differentiate cardiac amyloidosis (CA) at diagnosis from hypertensive LV hypertrophy (LVH) by analysis of longitudinal myocardial deformation. METHODS: Thirty healthy controls (C), 30 newly diagnosed, never treated hypertensives with LVH (H-LVH), and 33 patients with CA at diagnosis underwent echo Doppler including speckle tracking-based automated function imaging (AFI). Averaged peak systolic global longitudinal strain (GLS, 18 segments) and basal, middle, and apical longitudinal strain (BLS, MLS, and ALS, respectively, six segments each) were calculated. RESULTS: Left ventricular mass index, relative wall thickness, and ejection fraction did not differ between H-LVH and CA. E/e' ratio was higher in CA than in H-LVH (P<.001) and C (P<.0001). GLS was lower in CA than in C (P<.0001), without difference with H-LVH. ALS did not differ among the three groups, MLS was significantly lower in both CA and H-LVH than in C but BLS was lower in CA compared to both H-LVH and C (both P<.0001). In the pooled population, E/e' was independently associated with BLS (beta=-0.54, P<.0001). At receiver operating curve analysis, CA was predicted by BLS<=-11.3% (sensitivity=63.3%, specificity=100%) and E/e'>=12.3 (sensitivity=69.7%, specificity=83.3%). The best AUC (=0.819) was obtained by the combination E/e'+BLS. CONCLUSIONS: Our findings highlight a real difference of E/e' ratio and longitudinal strain of LV basal segments between hypertensive LVH and CA, which could be used to differentiate the two diseases. PMID- 27277829 TI - L p Regularization for Bioluminescence Tomography Based on the Split Bregman Method. AB - PURPOSE: Bioluminescence tomography (BLT) is a promising in vivo optical imaging technique in preclinical research at cellular and molecular levels. The problem of BLT reconstruction is quite ill-posed and ill-conditioned. In order to achieve high accuracy and efficiency for its inverse reconstruction, we proposed a novel approach based on L p regularization with the Split Bregman method. PROCEDURES: The diffusion equation was used as the forward model. Then, we defined the objective function of L p regularization and developed a Split Bregman iteration algorithm to optimize this function. After that, we conducted numerical simulations and in vivo experiments to evaluate the accuracy and efficiency of the proposed method. RESULTS: The results of the simulations indicated that compared with the conjugate gradient and iterative shrinkage methods, the proposed method is more accurate and faster for multisource reconstructions. Furthermore, in vivo imaging suggested that it could clearly distinguish the viable and apoptotic tumor regions. CONCLUSIONS: The Split Bregman iteration method is able to minimize the L p regularization problem and achieve fast and accurate reconstruction in BLT. PMID- 27277828 TI - Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging. AB - PURPOSE: Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with 111indium, via the chelate diethylene triamine pentaacetic acid (DTPA). PROCEDURES: The necrosis avid properties of the radiotracer [111In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo. RESULTS: Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [111In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis. CONCLUSIONS: The radiotracer [111In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy. PMID- 27277830 TI - Hypotension and hypovolemia during hemodialysis: is the usual suspect innocent? AB - Hypotension during intermittent hemodialysis is common, and has been attributed to acute volume shifts, shifts in osmolarity, electrolyte imbalance, temperature changes, altered vasoregulation, and sheer hypovolemia. Although hypovolemia may intuitively seem a likely cause for hypotension in intensive care patients, its role in the pathogenesis of intradialytic hypotension may be overestimated. PMID- 27277831 TI - Prevalence of Plasmodium spp. in illegal gold miners in French Guiana in 2015: a hidden but critical malaria reservoir. AB - BACKGROUND: Malaria is endemic in French Guiana, an overseas territory of France on the Guiana Shield. Since 2005, notified malaria cases are decreasing. However, new data show that malaria affects many Brazilian gold miners working illegally in French Guiana, the majority of whom are not counted in official data. In addition, one major concern is the usual practice of improper self-treatment in this mining population, raising fear of the development of anti-malarial resistance. This prospective study, conducted in 2015, aimed to estimate the prevalence of Plasmodium spp. in illegal gold miners working in French Guiana. METHODS: The recruitment of gold miners was carried out in resting sites along the French Guiana-Suriname border, where they go for supplies, medical care or leisure. After recording agreement, three malaria diagnostic methods were performed: rapid diagnostic test, microscopy and PCR. RESULTS: Among 421 persons recruited in the study, malaria prevalence, detected by nested-PCR, was 22.3 % (CI [18.3-26.3], n = 94/421) of which 84 % were asymptomatic. CONCLUSIONS: This significant malaria reservoir in a mobile and illegal population with difficult access to a health care system raises the threat of artemisinin resistance and puts the population of the Guiana Shield at risk of new transmission foci while countries of the region aim at malaria elimination. Even though French legislation may hamper dealing with this population, France must face the reality of malaria in illegal gold miners in order to meet its commitment to malaria elimination. PMID- 27277832 TI - In situ starch and crude protein degradation in the rumen and in vitro gas production kinetics of wheat genotypes. AB - The objective of this study was to determine the variation of in situ ruminal degradation characteristics of dry matter (DM), crude protein (CP) and starch (ST), and to determine the effective degradation (ED) of wheat genotypes. Further, multivariate associations of these in situ values with their corresponding in vitro gas production (GP) kinetics and laboratory measurements were evaluated using correlation and multiple linear regression analyses. Grains of 20 genotypes of wheat were characterized by proximate constituents, amino acid (AA) composition and physical characteristics. Ruminal degradation kinetics were determined by in situ degradation of DM, CP and ST, and subsequent evaluation of in vitro GP relative to time courses. In situ and GP measurements were fitted to an exponential equation, and ED was calculated using passage rates in the rumen of 5%/h (ED5) and 8%/h (ED8). To predict ED8 of CP (EDCP8) and ST (EDST8), correlations were evaluated and stepwise multiple linear regression analyses were applied. Estimated degradation parameters varied considerably between wheat genotypes irrespective of the nutrient tested. Variance in a, b and c was not reflected in the variation of the ED, due to high degradation rates (c). The assumed passage rate also impacted estimation of the ED minimally. Estimated GP parameters varied only slightly among wheat genotypes. Nevertheless, regression models explained up to 80 and 99% of the variance in EDCP8 and EDST8, respectively, and associations between EDST8 and EDCP8 and chemical and physical characteristics of grains were detected. As ST is the primary nutrient in wheat grains and can comprise substantial portions of dairy rations, the total amount of ST as well as its ED in the rumen should be taken into account when wheat is incorporated into dairy rations. Conversely, variance in wheat grain CP degradation was very low and can largely be neglected in practical ration formulation for ruminants. PMID- 27277834 TI - Constraints on mountain building in the northeastern Tibet: Detrital zircon records from synorogenic deposits in the Yumen Basin. AB - The Cenozoic basins and ranges form the high topography of the northeastern Tibet that resulted from the India-Eurasia collision. Sedimentary rocks in the basins provide direct insight into the exhumation history of the ranges and the tectonic processes that led to the northeastward growth of the Tibetan Plateau. In this study, we analyzed and compared detrital zircon U-Pb ages from sands of modern rivers draining the Bei Shan, and North Qilian Shan and sandstones from the Yumen Basin. The zircon age distributions indicate that the strata dated to 24.2-16.7 Ma in the basin were derived from the Bei Shan, and the basin provenance changed rapidly to the North Qilian Shan terrane at ~16 Ma. These results suggest that an early stage of deformation along the Bei Shan at ~24 Ma was replaced by the growth of the North Qilian Shan at ~16 Ma. We conclude that the far-field effect associated with the Indo-Asian collision may result from Oligocene deformation in the Bei Shan, but the emergence of the North Qilian Shan at ~16 Ma could reflect the most recent outward growth of the Tibetan Plateau that may have been caused by the removal of some lithospheric mantle beneath central Tibet. PMID- 27277833 TI - Mechanisms of brief contact interventions in clinical populations: a systematic review. AB - BACKGROUND: Brief Contact Interventions (BCIs) have been of increasing interest to suicide prevention clinicians, researchers and policy makers. However, there has been no systematic assessment into the mechanisms underpinning BCIs. The aim of the current paper is to provide a systematic review of the proposed mechanisms underpinning BCIs across trial studies. METHOD: A systematic review was conducted of trials using BCIs (post-discharge telephone contacts; emergency or crisis cards; and postcard or letter contacts) for suicide or self-harm. Following PRISMA guidelines, we searched CENTRAL, MEDLINE, EMBASE, and the reference lists of all past reviews in the area. Secondary searches of reference lists were undertaken. RESULTS: Sixteen papers provided a description of possible mechanisms which we grouped into three main areas: social support; suicide prevention literacy, and; learning alternative coping behaviours. After assessment of the studies and considering the plausibility of mechanisms, we suggest social support and improved suicide prevention literacy are the most likely mechanisms underpinning BCIs. CONCLUSION: Researchers need to better articulate and measure the mechanisms they believe underpin BCIs in trial studies. Understanding more about the mechanisms of BCIs' will inform the development of future interventions for self-harm and suicide. PMID- 27277835 TI - Regulation of the RhoA/ROCK/AKT/beta-catenin pathway by arginine-specific ADP ribosytransferases 1 promotes migration and epithelial-mesenchymal transition in colon carcinoma. AB - Arginine-specific ADP-ribosytransferases 1 (ART1) is able to modify the arginine of specific proteins by mono-ADP-ribosylation. We previously reported that the expression of ART1 in human colon adenocarcinoma tissues was higher than in adjacent tissues. Herein, we primarily revealed that ART1 could regulate the epithelial-mesenchymal transition (EMT) and, therefore, the development of colon carcinoma. In CT26 cells, which overexpressed ART1 by lentiviral transfection, the following were promoted: alterations of spindle-like non-polarization, expression of EMT inducers and mesenchymal markers, migration, invasion and adhesion. However, epithelial marker expression was decreased. Correspondingly, knockdown of ART1 in CT26 cells had the opposite effects. The effect of ART1 on EMT and carcinoma metastasis was also verified in a liver metastasis model of BALB/c mice. To further explore the molecular mechanism of ART1 in EMT, CT26 cells were treated with several specific inhibitors and gene silencing. Our data suggest that ART1 could regulate EMT by regulating the RhoA/ROCK1/AKT/beta catenin pathway and its downstream factors (snail1, vimentin, N-cadherin and E cadherin) and that it therefore plays an important role in the progression of colon carcinoma. PMID- 27277837 TI - [Not Available]. PMID- 27277836 TI - Normalization of network connectivity in hemispatial neglect recovery. AB - OBJECTIVE: We recently reported that spatial and nonspatial attention deficits in stroke patients with hemispatial neglect are correlated at 2 weeks postonset with widespread alterations of interhemispheric and intrahemispheric functional connectivity (FC) measured with resting-state functional magnetic resonance imaging across multiple brain networks. The mechanisms underlying neglect recovery are largely unknown. In this study, we test the hypothesis that recovery of hemispatial neglect correlates with a return of network connectivity toward a normal pattern, herein defined as "network normalization." METHODS: We measured attention deficits with a neuropsychological battery and FC in a large cohort of stroke patients at, on average, 2 weeks (n = 99), 3 months (n = 77), and 12 months (n = 64) postonset. The relationship between behavioral improvement and changes in FC was analyzed both in terms of a priori regions and networks known to be abnormal subacutely and in a data-driven manner. RESULTS: Attention deficit recovery was mostly complete by 3 months and was significantly correlated with a normalization of abnormal FC across many networks. Improvement of attention deficits, independent of initial severity, was correlated with improvements of previously depressed interhemispheric FC across attention, sensory, and motor networks, and a restoration of the normal anticorrelation between dorsal attention/motor regions and default-mode/frontoparietal regions, particularly in the damaged hemisphere. INTERPRETATION: These results demonstrate that abnormal network connectivity in hemispatial neglect is behaviorally relevant. A return toward normal network interactions, and presumably optimal information processing, is therefore a systems-level mechanism that is associated with improvements of attention over time after focal injury. Ann Neurol 2016;80:127 141. PMID- 27277838 TI - 'Just wait then and see what he does': a speech act analysis of healthcare professionals' interaction coaching with parents of children with autism spectrum disorders. AB - BACKGROUND: There is evidence indicating that parent training programmes including interaction coaching of parents of children with autism spectrum disorders (ASD) can increase parental responsiveness, promote language development and social interaction skills in children with ASD. However, there is a lack of research exploring precisely how healthcare professionals use language in interaction coaching. AIMS: To identify the speech acts of healthcare professionals during individual video-recorded interaction coaching sessions of a Hanen-influenced parent training programme with parents of children with ASD. METHODS & PROCEDURES: This retrospective study used speech act analysis. Healthcare professional participants included two speech-language therapists and one occupational therapist. Sixteen videos were transcribed and a speech act analysis was conducted to identify the form and functions of the language used by the healthcare professionals. Descriptive statistics provided frequencies and percentages for the different speech acts used across the 16 videos. OUTCOMES & RESULTS: Six types of speech acts used by the healthcare professionals during coaching sessions were identified. These speech acts were, in order of frequency: Instructing, Modelling, Suggesting, Commanding, Commending and Affirming. The healthcare professionals were found to tailor their interaction coaching to the learning needs of the parents. A pattern was observed in which more direct speech acts were used in instances where indirect speech acts did not achieve the intended response. CONCLUSIONS & IMPLICATIONS: The study provides an insight into the nature of interaction coaching provided by healthcare professionals during a parent training programme. It identifies the types of language used during interaction coaching. It also highlights additional important aspects of interaction coaching such as the ability of healthcare professionals to adjust the directness of the coaching in order to achieve the intended parental response to the child's interaction. The findings may be used to increase the awareness of healthcare professionals about the types of speech acts used during interaction coaching as well as the manner in which coaching sessions are conducted. PMID- 27277841 TI - Program Abstracts: American Headache Society(r) 58th Annual Scientific Meeting. PMID- 27277840 TI - Cardiac masses and tumours. PMID- 27277843 TI - (68)Ga-PSMA ligand PET/CT in patients with prostate cancer: How we review and report. AB - Recently, positron emission tomography (PET) imaging using PSMA-ligands has gained high attention as a promising new radiotracer in patients with prostate cancer (PC). Several studies promise accurate staging of primary prostate cancer and restaging after biochemical recurrence with (68)Ga-PSMA ligand Positron emission tomography/computed tomography (PET/CT). However, prospective trials and clinical guidelines for this new technique are still missing. Therefore, we summarized our experience with (68)Ga-PSMA ligand PET/CT examinations in patients with primary PC and biochemical recurrence. It focuses on the technical and logistical aspects of (68)Ga-PSMA ligand PET/CT examination as well as on the specific background for image reading discussing also potential pitfalls. Further, it includes relevant issues on free-text as well as structured reporting used in daily clinical routine. PMID- 27277839 TI - HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4(+) T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial. AB - BACKGROUND: Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. METHODS: The ISS T-003 was a 48 week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 MUg) given intradermally, three times at 4-week intervals, in 200 HIV infected adults on effective cART (randomised 1:1) with CD4(+) T-cell counts >=200 cells/uL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4(+) T-cell counts and therapy compliance. RESULTS: Immunization was safe and well-tolerated and induced durable, high titers anti Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4(+) T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4(+) T cell numbers over study entry levels as compared to placebo. CONCLUSIONS: The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. Trial registration ClinicalTrials.gov NCT01513135, 01/23/2012. PMID- 27277844 TI - Tanshinone IIA decreases the protein expression of EGFR, and IGFR blocking the PI3K/Akt/mTOR pathway in gastric carcinoma AGS cells both in vitro and in vivo. AB - Tan-IIA exerts powerful inhibitory effects in gastric cancer AGS cells. The PI3K/AKT/mTOR pathway is one of the most frequently dysregulated kinase cascades in human cancer. In the present study, we investigated the protein expression levels of PI3K, AKT and mTOR in AGS cells treated with Tan-IIA both in vitro and in vivo. The AGS cells were treated with Tan-IIA for different durations in vitro. In the in vivo study, AGS cell xerograft SCID mice were treated with Tan IIA for 8 weeks. Subsequently, the protein expression of EGFR, IGFR, PI3K, AKT and mTOR was measured by western blotting. The results showed that Tan-IIA was able to decrease the protein expression levels of EGFR, IGFR, PI3K, AKT and mTOR significantly and dose-dependently in vitro and in vivo. In conclusion, these findings indicate Tan-IIA could inhibit AGS cells through decreasing the protein expression of EGFR, IGFR and blocking PI3K/AKT/mTOR pathway both in vitro and in vivo. PMID- 27277845 TI - Chronic Kidney Disease Alters Vitamin A Homeostasis via Effects on Hepatic RBP4 Protein Expression and Metabolic Enzymes. AB - Vitamin A, via retinoic acid (RA), is a critical micronutrient. Normally, plasma concentrations are tightly regulated. Concentrations of vitamin A metabolites (13cis-RA, atRA) and relationships between RBP4 and retinoids have never been fully evaluated in adult patients with CKD. We measured retinoid and RBP4 concentrations in plasma and urine from 55 adult patients with CKD and 21 matched healthy subjects. RBP4 and retinol levels were increased approximately twofold in patients with CKD, with a negative correlation between plasma retinol and eGFR (p = 0.006) and plasma RBP4 and eGFR (p = 0.0007). RBP4 renal clearance was higher in patients with CKD than healthy subjects but not associated with eGFR. Circulating concentrations of atRA increased and concentrations of 13cis-RA decreased in subjects with CKD with no change in RA-to-retinol ratio. Increases in circulating retinol, RBP4, and atRA may be due to increased hepatic RBP4 synthesis, retinyl ester hydrolysis, and/or hepatic secretion of RBP4-retinol. PMID- 27277846 TI - Inflammatory Markers of CRP, IL6, TNFalpha, and Soluble TNFR2 and the Risk of Ovarian Cancer: A Meta-analysis of Prospective Studies. AB - BACKGROUND: There has been growing evidence showing that inflammatory markers play an important role in the development of ovarian cancer. We conducted a meta analysis on the associations between circulating levels of C-reactive protein (CRP), interleukin 6 (IL6), tumor necrosis factor alpha (TNFalpha), and soluble TNFalpha receptor 2 (TNFR2), and the risk of ovarian cancer. METHODS: A systematic search of PubMed and EMBASE up until January 19, 2016 was conducted to retrieve prospective studies. The summary risk estimates were pooled using random effects models. The dose-response relationship was assessed using generalized least-squares trend estimation. RESULTS: Seven nested case-control studies and one prospective cohort study were included in the review. For circulating CRP, women in the highest category had a significantly increased risk of ovarian cancer than women in the lowest category, with no significant between-study heterogeneity [pooled relative risk (RR) = 1.91; 95% confidence intervals (CI) 1.51-2.40; P < 0.001; I(2) = 0.0%]. Influence analyses further supported this positive association. A positive dose-response relationship was also observed (pooled RR = 1.15; 95% CI, 1.03-1.30 per 5 mg/L of CRP). Publication bias was found. However, the association persisted after correction using the trim-and fill method. No significant association was observed for circulating IL6, TNFalpha, and soluble TNFR2. CONCLUSION: This meta-analysis provides evidence that elevated levels of CRP, but not circulating IL6, TNFalpha, or soluble TNFR2, are significantly associated with an increased risk of ovarian cancer. IMPACT: These results suggest that circulating CRP may play a role in the etiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev; 25(8); 1231-9. (c)2016 AACR. PMID- 27277848 TI - Screening ultrasonic examination. PMID- 27277847 TI - Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers. AB - BACKGROUND: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1/2 mutation on the breast cancer lifetime risk, when adjusted for referral bias. METHODS: A Dutch national cohort including 1,314 proven BRCA1/2 mutation carriers and covering 54,752 person years. Data were collected by family cancer clinics, via questionnaires and from the national Dutch Cancer Registry. The parent-of-origin effect was assessed using Cox regression analyses, both unadjusted and adjusted for referral bias. Referral bias was operationalized by number of relatives with cancer and by personal cancer history. RESULTS: The mutation was of paternal origin in 330 (42%, P < 0.001) BRCA1 and 222 (42%, P < 0.001) BRCA2 carriers. Paternal origin increased the risk of prevalent breast cancer for BRCA1 [HR, 1.54; 95% confidence interval (CI), 1.19-2.00] and BRCA2 carriers (HR, 1.40; 95% CI, 0.95-2.06). Adjusted for referral bias by several family history factors, these HRs ranged from 1.41 to 1.83 in BRCA1 carriers and 1.27 to 1.62 in BRCA2 carriers. Adjusted for referral bias by personal history, these HRs were 0.66 (95% CI, 0.25-1.71) and 1.14 (95% CI, 0.42-3.15), respectively. CONCLUSION: A parent-of-origin effect is present after correction for referral bias by family history, but correction for the personal cancer history made the effect disappear. IMPACT: There is no conclusive evidence regarding incorporating a BRCA1/2 parent-of-origin effect in breast cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 25(8); 1251-8. (c)2016 AACR. PMID- 27277849 TI - Ultrasound-mediated gene transfection: problems to be solved and future possibilities. AB - Together, the human genome project and advances in molecular biology have led to identification of many genes, some useful in the field of medicine. Gene therapy has opened a potentially new therapeutic avenue for managing an array of complicated diseases. One of the more critical areas of gene therapy is the design of an appropriate, accurate, and effective gene transfer system that can be safely applied in vivo. Because no known system meets all the requirements for clinical use, a better, more versatile method of gene transfer is desired. Ultrasound-mediated transfection (USMT) could serve as a potential site-specific gene transfer modality. Although no actual mechanism has yet been thoroughly described, we focus on the principles of USMT, discuss the use of microbubbles as a gene-transfer mechanism, and summarize preliminary in vivo experiments using microbubbles as vectors. Although the published data suggest the promise of this method, extensive improvement in USMT remains essential. Reassuringly, recent success in USMT research has positioned ultrasound as a highly safe modality for gene transfer. PMID- 27277850 TI - Measurement of nonlinear property of artery wall using remote cyclic actuation. AB - PURPOSE: For tissue characterization of the arterial wall, we developed a "phased tracking" method to measure the strain (change in wall thickness) and elasticity of the arterial wall. To improve the accuracy of tissue characterization, we are now attempting to measure other mechanical properties in addition to elasticity. METHODS: In this study, the change in elasticity during the cardiac diastole was measured with ultrasound by generating a change in internal pressure using remote cyclic actuation. RESULTS: From the measured change in elasticity during cardiac diastole, the nonlinear property in the stress-strain relationship of the artery wall was estimated. In basic experiments using a silicone rubber tube and in vivo experiments in human carotid arteries. CONCLUSION: The proposal method enables the noninvasive measurement of the nonlinear mechanical property in addition to the elasticity of the arterial wall. PMID- 27277851 TI - New method of sentinel node detection using a combination of contrast-enhanced ultrasound and dye guidance: an animal study. AB - PURPOSE: To determine whether a combination of contrast-enhanced ultrasound guided methods and dye-guided methods can identify sentinel lymph nodes in animals. METHODS: Seven pigs were put under general anesthesia and injected subcutaneously in the neck: three with 2 ml saline and four with 2 ml fluid comprising 0.4 ml 5% patent blue violet solution and 1.6 ml of hydroxyethylated starch (Salinhes) solution (PB + HS). The regional lymph nodes were observed by ultrasound; blue-stained regional lymph nodes found after the skin was cut were situated as ultrasound had shown they would be. RESULTS: The regional lymph nodes of the pigs given saline were unchanged, but in the pigs receiving PB + HS, the echo level in the lymph nodes nearest the injection site was altered, producing a clear contrast with the surrounding tissues. The area of the relevant regional lymph node in each PB + HS-injected pig increased significantly (t-test, P < 0.01; from 25.7, 39.6, 9.36, 70.2 mm(2), and mean, 36.2 mm(2); to 50.7, 65.5, 21.1, 98.3 mm(2), and mean, 58.9 mm(2), respectively). These enlarged regional lymph nodes were easily found by contrast-enhanced ultrasonography. When excised under ultrasound guidance, all were stained blue, indicating that they were sentinel lymph nodes. CONCLUSION: These results suggest that this combination of contrast-enhanced ultrasound-guided and dye-guided methods warrants use as a quick, simple procedure for detecting sentinel lymph nodes. PMID- 27277852 TI - A case with diffuse sclerosing variant of papillary carcinoma of the thyroid: characteristic features on ultrasonography. AB - We describe the case of a patient who had a diffuse sclerosing variant of papillary carcinoma of the thyroid with characteristic features on ultrasonography. Most papillary thyroid carcinomas can be easily recognized and diagnosed by ultrasonography. The thyroid carcinoma in this patient, however, showed diffuse enlargement of the thyroid without formation of any masses, and it had hypoechoic and heterogeneous internal echoes, which contained fine and multiple high-echo spots. Multiple lymph nodes were found to be swollen in the bilateral jugular chains on B-mode ultrasonography. It is very important that this type of papillary carcinoma with characteristic clinical features be detected by careful examination. PMID- 27277853 TI - Development of severe string sign in internal thoracic arterial graft during first month. AB - In the present case, development of the string sign in an internal thoracic arterial graft was observed using transthoracic Doppler echocardiography. Following surgery, the diameter of the internal thoracic graft decreased; however, the diameter of the left anterior descending coronary artery did not change from 1.9 mm. Further, the flow velocity in the internal thoracic artery during the systolic phase became greater than that in the early phase and then decreased on postoperative day 19, and it was not detected on postoperative day 31. Coronary arteriography performed on postoperative day 31 revealed a severely stringed internal thoracic artery. PMID- 27277855 TI - Isolated liver metastasis from a renal cell carcinoma 12 years after nephrectomy: report of a case and literature review. AB - We present a rare case of isolated liver metastasis from renal cell carcinoma 12 years after complete resection of the primary site. Such abnormal behavior of renal cell carcinoma has been reported elsewhere in the literature; thus, careful long-term surveillance should be performed in patients with a past history of renal cell carcinoma, even after radical resection of the primary site. We present also contrast-enhanced sonographic findings for this case. PMID- 27277854 TI - Marked change in Doppler waveform: report of two cases of subcutaneous hematoma. AB - We present two cases of subcutaneous hematoma in which color Doppler US revealed colored areas under probe compression, and Doppler waveforms obtained from these areas changed rapidly (from a constant flow to a pulsatile flow, and from a high velocity flow to a slow-velocity flow) according to the degree of probe compression. In our cases, a sufficient number of blood cells within the lesion moving under probe compression was thought to give rise to Doppler signals and changes in Doppler waveforms. PMID- 27277856 TI - Inflammatory pseudotumor of the spleen: report of a case with emphasis on contrast-enhanced ultrasound findings. AB - Splenic inflammatory pseudotumor is a rare pathology, and the literature stresses the difficulty of preoperative diagnosis. There are no previous reports of contrast-enhanced ultrasound findings for this tumor in the literature. Our case appears to be the first to be examined using this technique. In our case, contrast-enhanced ultrasound showed the mass to be homogeneously and less enhanced than the surrounding parenchyma in all phases, and it included fine enhanced spots. We also briefly review the literature. PMID- 27277857 TI - Portal-systemic shunt through the right renal vein developing following portal tumor thrombus. AB - Despite the semi-routine use of color Doppler sonography for evaluating portal circulation abnormalities, there is a relative paucity of information on portal systemic (P-S) shunt through the right renal vein (P-SR shunt). We report such a case. The patient was a 60-year-old woman with hepatocellular carcinoma on liver cirrhosis. Serial sonography showed an aggravation in findings; an increase in the size of the tumor was followed by formation of a portal tumor thrombus, and then occurrence of a P-SR shunt. We present this case, with a comparison between the patient's clinical course and the color Doppler results. To our knowledge, this is the first report to make such a comparison in a P-SR shunt case. We also briefly review the literature. PMID- 27277858 TI - Ultrasonographic findings for ovarian teratoma. PMID- 27277859 TI - Gallbladder varices. PMID- 27277860 TI - Peritoneal loose body. PMID- 27277861 TI - Guidelines for image presentation and measurement of the ophthalmic region (proposal). PMID- 27277862 TI - Polyomavirus BK Induces Inflammation via Up-regulation of CXCL10 at Translation Levels in Renal Transplant Patients with Nephropathy. AB - Polyomavirus BK-associated nephropathy (BKAN) is an important mechanism for renal losing after kidney transplantation. It seems that Polyomavirus BK can induce nephropathy by direct cell lysis and stimulation of the immune system and induction of inflammation. CXCL10 is a pro-inflammatory cytokine which stimulates the migration and activation of immune cells to the infected sites. Therefore, the aim of the current study was to evaluate the messenger RNA (mRNA) and protein levels of CXCL10 in the Polyomavirus BK-infected and Polyomavirus BK-non-infected post renal transplanted nephropathic patients in comparison to healthy controls. In this cross-sectional study, Polyomavirus BK-infected post renal transplanted nephropathic patients, Polyomavirus BK-non-infected post renal transplanted nephropathic patients, and healthy controls were enrolled to evaluate mRNA and protein levels of CXCL10 by real-time PCR and ELISA techniques, respectively. mRNA levels of CXCL10 were not significantly different among participants, while serum levels of CXCL10 were significantly elevated in the Polyomavirus BK infected patients when compared to non-infected patients as well as controls and in non-infected patients when compared to healthy controls. Due to the results, it seems that Polyomavirus BK may potentially induce renal losing through stimulation of inflammation via increasing translation of CXCL10, as a pro inflammatory chemokine. PMID- 27277863 TI - Genome-wide analysis for identification of adaptive diversification between hepatitis C virus subtypes 1a and 1b. AB - Hepatitis C virus (HCV) is a major cause of liver disease and has been estimated to infect approximately 2%-3% of the world's population. HCV genotype 1 is the subject of intense research and clinical investigations because of its worldwide prevalence and poor access to treatment for patients in developing countries and marginalized populations. The predominant subtypes 1a and 1b of HCV genotype 1 present considerable differences in epidemiological features. However, the genetic signature underlying such phenotypic functional divergence is still an open question. Here, we performed a genome-wide evolutionary study on HCV subtypes 1a and 1b. The results show that adaptive selection has driven the diversification between these subtypes. Furthermore, the major adaptive divergence-related changes have occurred on proteins E1, NS4B, NS5A, and NS5B. Structurally, a number of adaptively selected sites cluster in functional regions potentially relevant to (i) membrane attachment and (ii) the interactions with viral and host cell factors and the genome template. These results might provide helpful hints about the molecular determinants of epidemiological divergence between HCV 1a and 1b. PMID- 27277864 TI - Erratum to: Patterns and correlates of accelerometer-assessed physical activity and sedentary time among colon cancer survivors. PMID- 27277865 TI - Erratum to: Variants of EVER1 and EVER2 (TMC6 and TMC8) and human papillomavirus status in patients with mucosal squamous cell carcinoma of the head and neck. PMID- 27277866 TI - Emotion regulation involves both model-based and model-free processes. PMID- 27277869 TI - Learning and memory: Once upon a recent time. PMID- 27277870 TI - Classifying emotion regulation strategies. PMID- 27277868 TI - Time to connect: bringing social context into addiction neuroscience. AB - Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant. PMID- 27277871 TI - Metabolism and bioactivation of the tricyclic antidepressant amitriptyline in human liver microsomes and human urine. AB - AIM: Amitriptyline is a widely used tricyclic antidepressant, but the metabolic studies were conducted almost 20 years ago using high-performance liquid chromatography coupled with ultraviolet detector or radiolabeled methods. RESULTS: First, multiple ion monitoring (MIM)- enhanced product ion (EPI) scan was used to obtain the diagnostic ions or neutral losses in human liver microsome incubations with amitriptyline. Subsequently, predicted multiple reaction monitoring (MRM)-EPI scan was used to identify the metabolites in human urine with the diagnostic ions or neutral losses. Finally, product ion filtering and neutral loss filtering were used as the data mining tools to screen metabolites. Consequently, a total of 28 metabolites were identified in human urine after an oral administration using LC-MS/MS. CONCLUSION: An integrated workflow using LC MS/MS was developed to comprehensively profile the metabolites of amitriptyline in human urine, in which five N-acetyl-l-cysteine conjugates were characterized as tentative biomarkers for idiosyncratic toxicity. PMID- 27277872 TI - Salvia divinorum: toxicological aspects and analysis in human biological specimens. AB - The identification and quantitation of the main psychoactive component of Salvia divinorum (salvinorin A) in biological specimens are crucial in forensic and clinical toxicology. Despite all the efforts made, its uncontrolled abuse has increased quickly, exposing its users' health to serious risks both in the short and long term. The use of alternative biological matrices in toxicological analyzes can be advantageous as complementary postmortem samples, or in situations when neither blood nor urine can be collected; they may be useful tools in those determinations, providing important information about prior exposure. The aim of this article is to present a brief summary of legal aspects of Salvia divinorum and salvinorin A, including the methods used for the determination of the latter in biological matrices. PMID- 27277867 TI - Integrating neuroimmune systems in the neurobiology of depression. AB - Data from clinical and preclinical studies indicate that immune dysregulation, specifically of inflammatory processes, is associated with symptoms of major depressive disorder (MDD). In particular, increased levels of circulating pro inflammatory cytokines and concomitant activation of brain-resident microglia can lead to depressive behavioural symptoms. Repeated exposure to psychological stress has a profound impact on peripheral immune responses and perturbs the function of brain microglia, which may contribute to neurobiological changes underlying MDD. Here, we review these findings and discuss ongoing studies examining neuroimmune mechanisms that influence neuronal activity as well as synaptic plasticity. Interventions targeting immune-related cellular and molecular pathways may benefit subsets of MDD patients with immune dysregulation. PMID- 27277873 TI - Adaptation of hybrid immunoaffinity LC-MS methods for protein bioanalysis in a Contract Research Organization. PMID- 27277874 TI - Quantification of 18 amino acids in human plasma: application in renal transplant patient plasma by targeted UHPLC-MS/MS. AB - AIM: Quantification of amino acids in human plasma has become an important and essential analysis parameter in life science. In this paper, we developed a targeted UHPLC-MS/MS method for 18 amino acids in the renal transplant patients. METHODS & RESULTS: Plasma in small volume (150 MUl) was pretreated by a one-step protein precipitant extraction for analysis. Detection was executed by MS/MS in the MRM mode. Assays were validated according to current bioanalytical guidelines, with good linearity (R > 0.99), intraday and interday precision (CV < 11.6%, RE <= +/- 14.8%), extraction recovery (between 77.4 and 117.6%), matrix effect (73.3-118.0%) and stability (RE<= +/-14.7%). CONCLUSION: The method was successfully applicable for amino acid analysis in the renal transplant patient. PMID- 27277875 TI - Real-time monitoring of exhaled volatiles using atmospheric pressure chemical ionization on a compact mass spectrometer. AB - AIM: Breath analyses have potential to detect early signs of disease onset. Ambient ionization allows direct combination of breath gases with MS for fast, on line analysis. Portable MS systems would facilitate field/clinic-based breath analyses. Results & methodology: Volunteers ingested peppermint oil capsules and exhaled volatile compounds were monitored over 10 h using a compact mass spectrometer. A rise and fall in exhaled menthone was observed, peaking at 60-120 min. Real-time analysis showed a gradual rise in exhaled menthone postingestion. Sensitivity was comparable to established methods, with detection in the parts per trillion range. CONCLUSION: Breath volatiles were readily analyzed on a portable mass spectrometer through a simple inlet modification. Induced changes in exhaled profiles were detectable with high sensitivity and measurable in real time. PMID- 27277876 TI - Bioanalytical method transfer considerations of chromatographic-based assays. AB - Bioanalysis is an important part of the modern drug development process. The business practice of outsourcing and transferring bioanalytical methods from laboratory to laboratory has increasingly become a crucial strategy for successful and efficient delivery of therapies to the market. This chapter discusses important considerations when transferring various types of chromatographic-based assays in today's pharmaceutical research and development environment. PMID- 27277878 TI - Squeezing more value from the analytes we have: personal baselines for multiple analytes in serial DBS. PMID- 27277877 TI - Development and validation of a UPLC-MS/MS method for the simultaneous determination of paritaprevir and ritonavir in rat liver. AB - AIM: Determination of paritaprevir and ritonavir in rat liver tissue samples. RESULTS: We successfully validated a UPLC-MS/MS method to measure paritaprevir and ritonavir in rat liver using deuterated internal standards (d8-paritapervir and d6-ritonavir). The method is linear from 20 to 20,000 and 5 to 10,000 pg on column for paritaprevir and ritonavir, respectively, and is normalized per milligram tissue. Interday and intraday variability ranged from 0.591 to 5.33% and accuracy ranged from -6.68 to 10.1% for quality control samples. The method was then applied to the measurement of paritaprevir and ritonavir in rat liver tissue samples from a pilot study. CONCLUSION: The validated method is suitable for measurement of paritaprevir and ritonavir within rat liver tissue samples for PK studies. PMID- 27277880 TI - Ultrasound and its psychological effects. PMID- 27277879 TI - Antibody-drug conjugate bioanalysis using LB-LC-MS/MS hybrid assays: strategies, methodology and correlation to ligand-binding assays. AB - BACKGROUND: Antibody-drug conjugates (ADCs) are complex drug constructs with multiple species in the heterogeneous mixture that contribute to their efficacy and toxicity. The bioanalysis of ADCs involves multiple assays and analytical platforms. METHODS: A series of ligand binding and LC-MS/MS (LB-LC-MS/MS) hybrid assays, through different combinations of anti-idiotype (anti-Id), anti-payload, or generic capture reagents, and cathepsin-B or trypsin enzyme digestion, were developed and evaluated for the analysis of conjugated-payload as well as for species traditionally measured by ligand-binding assays, total-antibody and conjugated-antibody. RESULTS & CONCLUSION: Hybrid assays are complementary or viable alternatives to ligand-binding assay for ADC bioanalysis and PK/PD modeling. The fit-for-purpose choice of analytes, assays and platforms and an integrated strategy from Discovery to Development for ADC PK and bioanalysis are recommended. PMID- 27277881 TI - Arterial blood flow occlusion by high intensity focused ultrasound and histologic evaluation of its effect on arteries and surrounding tissues. AB - High intensity focused ultrasound (HIFU) has been used in a number of clinical studies. High intensity focused ultrasound could become the minimally invasive tumor therapy of choice if it could be used to occlude the feeding arteries of tumors by exposure from outside the body. We used high intensity focused ultrasound to insonate the femoral arteries of both thighs of 18 male and female Sprague-Dawley (SD) rats, at frequencies of 1 or 3 MHz. Duration of exposure to high intensity focused ultrasound was 5 or 10 seconds. The femoral artery that was exposed to high intensity focused ultrasound was resected immediately after or 24 hours, 48 hours, or 12 days (at 1 MHz) after insonation. Arterial blood flow occlusion was achieved at 3 MHz, but not at 1 MHz. Free-field spatial peak intensity was 800 W/cm(2) at 1 MHz and 10 kW/cm(2) at 3 MHz. Histologic examination of the resected specimen showed that changes varied with ultrasound frequency and time course after exposure to high intensity focused ultrasound. We suggest that high intensity focused ultrasound might prove useful in occluding arteries when treating tumors in the clinical setting. PMID- 27277882 TI - Qualitative and quantitative analysis of portal Doppler waveform and a novel factor of portal pulsatility: Systolic spike wave. AB - BACKGROUND: We attempted to identify the physiologic circumstances associated with the portal Doppler waveform. METHOD: The subjects were 98 patients: 42 had cirrhosis; 23, hepatitis; and 33, no liver disorder. We measured right portal venous peak velocity, minimum velocity, and hepatic arterial peak systolic velocity. Portal venous pulsatility was calculated as portal venous minimum velocity divided by portal venous peak velocity. We analyzed portal waveforms both qualitatively and quantitatively. RESULTS: Portal Doppler waveforms were classified as nonphasic, monophasic, biphasic, biphasic including spike wave, and triphasic. Portal waveforms were phasic in 84 subjects who had a mild systolic dip during the arterial systolic period. Markedly portal pulsatility (portal venous pulsatility<0.6) was present in only 7 subjects. A systolic spike wave corresponding to a hepatic arterial peak systolic wave was detected in 48 subjects. Hepatic arterial peak systolic velocity was significantly higher in the group with spike wave than in the group without it. CONCLUSION: Although portal pulsatility is generally attributed to multiple factors, the present study has pointed out a new factor; transmission via the hepatic artery through the portal vein vasa vasorum. Hepatic venous drainage and hepatic arterial blood flow influence portal waveform. PMID- 27277883 TI - Contrast-enhanced ultrasonography using levovist: Usefulness of diagnosis of small focal nodular hyperplasia lesions. AB - Differential diagnosis of focal nodular hyperplasia and hepatocellular carcinoma is clinically important because, while both are hypervascular tumors, they have vastly different prognoses. Because the spoke-wheel appearance is the primary characteristic of focal nodular hyperplasia, we attempted to detect this pattern in nodules smaller than 3 cm in diameter with contrast-enhanced ultrasonography using a contrast agent (Levovist). Four patients were examined with contrast enhanced US: two of the patients were examined with Coded Harmonic Angio; the other two patients were examined with contrast-enhanced color and power Doppler US without harmonic imaging. Although the hepatic arteriogram showed the spoke wheel appearance in only one tumor (diameter, 3 cm), contrast-enhanced US clearly demonstrated this characteristic in all four tumors, including three tumors that were less than 2 cm in diameter. Because it is noninvasive and can be carried out in an outpatient clinic, contrast-enhanced US is extremely useful for diagnosing small focal noduler hyperplasia lesions at sites that can be observed with US. PMID- 27277884 TI - Gallbladder carcinoma with ultrasonographically intact outer hyperechoic layer: A sign of a favorable outcome. AB - Thirty-one of 40 patients with gallbladder carcinoma whom we treated from December 1983 through June 1999 underwent resection of cancers extending from the mucosa (m) (pTis-pT1a) to the subserosa (ss) (pT2). The patients were classified into five groups according to the layered-structure of the gallbladder wall and the internal echo of tumors visualized in ultrasound images. Group A included pedunculated polyps with round margins, homogeneous hypoechoic internal echoes, and intact outer hyperechoic layers; group B, broad-based lesions with homogeneous hypoechoic internal echoes and intact outer hyperechoic layers; group C, broad-based lesions with intact outer hyperechoic layers and more heterogeneous hypoechoic internal echoes in their centers than those in the marginal lesions; group D, broad-based lesions with irregularity and/or thinning of outer hyperechoic layers; and group E, tumors that could not be evaluated. The ultrasonograms and histopathologic findings of groups A through D were compared, and the surgical techniques used in each group were examined. Outcomes achieved by groups A through C, with their intact outer hyperechoic layers, were compared with those achieved by groups D and E.The six tumors in group A were all well differentiated adenocarcinomas confined to the mucosa (pTis), and simple cholecystectomy was considered appropriate. The eight tumors in group B comprised three cases of m (pTis-pT1a) cancer, two cases of cancer invading the muscularis propria (mp) (pT1b), and three cases of cancer minutely scattered in the infiltrating subserosal fibrous layer (ss fibrous layer) (pT2). Accordingly, because of the difficulty of determining depth of invasion, resection of the liver bed was considered appropriate in group B. Histopathologic examination of group C showed that the tumors had invaded the ss fibrous layer (pT2) in all six patients. Although the ss fat layer had not been invaded, metastasis to the lymph nodes of the cystic duct (30%) had occurred, suggesting that a favorable outcome could be expected if the patient underwent resection of the liver bed and lymphadenectomy of the cystic duct, pericholedochal, hilar, peripancreatic, periportal, common hepatic, and proper hepatic lymph nodes. Group D comprised two patients with cancers that had invaded the ss fat layer (pT2). All nine tumors in group E were ss (pT2) cancers. The 5-year survival rate was 100 percent in groups A, B, and C; 50 percent in group D, and 45 percent in group E. Five-year survival rates were significantly lower in groups D and E than in groups A, B, and C, in which the outer hyperechoic layer remained intact (p<0.01).Gallbladder carcinomas with intact outer hyperechoic layers were classified into three groups (groups A, B, and C), in which depth of invasion ranged from m (pTis-pT1a) to the ss fibrous layer (pT2). These three groups were associated with favorable outcomes, although different surgical techniques were required for each group. An intact outer hyperechoic layer in the ultrasonogram is a predictor of a favorable outcome in patients with gallbladder carcinoma. PMID- 27277885 TI - Prenatal diagnosis and antenatal history of persistent truncus arteriosus: A case report. AB - We report the prenatal diagnosis and the natural history of a fetus with truncus arteriosus. A 31-year-old woman, gravida 3, was referred for detailed examination for suspected cardiac anomaly during her 33rd week of gestation. Fetal echocardiography demonstrated a large truncal vessel overriding a ventricular septal defect, a right-side aortic arch, and a dilated ascending aortic arch. Pulsed-wave and color-flow Doppler imaging showed truncal valvular stenosis without insufficiency. No sign of congestive heart failure was detected during the prenatal period. A fetus weighing 2860 grams was delivered during the 38th week of gestation. Cyanosis was noted the day after delivery, however, and a Rastelli procedure was carried out 9 days after delivery. The baby died 7 days after the operation. PMID- 27277886 TI - Real time tissue elasticity imaging using the combined autocorrelation method. AB - The elastic properties of tissues are expected to provide novel information for use in diagnosing pathologic changes in tissues and discriminating between malignant and benign tumors. Because it is hard to directly estimate the elastic modulus distribution from echo signals, methods for imaging the distribution of tissue strain under static compression are being widely investigated. Imaging the distribution of strain has proven to be useful for detecting disease tissues on the basis of their differences in elastic properties, although it is more qualitative than elastic modulus distribution. Many approaches to obtaining strain images from echo signals have been proposed. Most of these approaches use the spatial correlation technique, a method of detecting tissue displacement that provides maximum correlation between the echo signal obtained before and the one obtained after compression. Those methods are not suited for real-time processing, however, because of the amount of computation time they require. An alternative approach is a phase-tracking method, which is analogous to Doppler blood flowmetry. Although it can realize the rapid detection of displacement, the aliasing effect prevents its application to the large displacements that are necessary to improve the S/N ratio of the strain image. We therefore developed a more useful technique for imaging tissue elasticity. This approach, which we call the combined autocorrelation (CA) method, has the advantages of producing strain images of high quality with real-time processing and being applicable to large displacements.Numeric simulation and phantom experimentation have demonstrated that this method's capability to reconstruct images of tissue strain distribution under practical conditions is superior to that of the conventional spatial correlation method. In simulation and phantom experimentation, moreover, the image of elastic modulus distribution was also obtained by estimating stress distribution using a three-dimensional tissue model. When the proposed CA method was used to measure breast tumor specimens, the obtained strain images clearly revealed harder tumor lesions that were only vaguely resolved in B-mode images. Moreover, the results indicated the possibility of extracting the pathological characteristics of a tumor, making it useful for determining tumor type. These advantages justify the clinical use of the CA method. PMID- 27277887 TI - Noninvasive measurement of stiffness and density of bone for its diagnosis using ultrasound. AB - Because the acoustic and elastic properties of bone evaluated using ultrasound based methods have proved so useful in the direct evaluation of bone characteristics, many workers have developed methods and systems based on thein vivo measurement of velocity, attenuation, or both, of ultrasound in bone. These include the acoustic emission (AE), apparent velocity of ultrasound (AVU), and speed of sound-broadband ultrasound attenuation (SOS-BUA) methods. Bone stiffness is accepted as an effective index in the diagnosis of such bone diseases as osteoporosis. The literature contains reports of the estimation of bone stiffness from velocity (speed of sound [SOS]) and attenuation (broadband ultrasound attenuation [BUA]). The physical explanation of the methods of evaluating stiffness from the obtained values of BUA and SOS is still not clear, however. Here we propose a new diagnostic method and system based on ultrasound measurement of the stiffness of bone. The proposed method determines stiffness from the velocity of the leaky surface skimming compressional waves (LSSCWs) obtained with the microdefocusing method and the acoustic impedance obtained with the reflectance method. Thus this method can evaluate stiffness without exposing the patient to X-rays; moreover, the physical basis of the calculation of stiffness from velocity and impedance is well understood. We applied this system to the human tibiain vivo: stiffness and density in a young volunteer were successfully evaluated at 24.9 GPa and 2.01*10(3) kg/m(3), respectively. PMID- 27277888 TI - Abdominal ultrasonogram of autoimmune pancreatitis: Five cases of pancreatic lesions accompanied by Sjogren syndrome. AB - The concept of autoimmune pancreatitis has recently been established, and ultrasonographic findings we obtained from five cases consistent with autoimmune pancreatitis are reported here. Case 1, a 77-year-old man, was admitted complaining of loss of body weight. Serum hepatobiliary enzymes and gamma globulin levels were elevated, and antinuclear antibody was positive, Abdominal ultrasonography showed dilatation of the intrahepatic bile duct, wall thickening of the common bile duct and hypoechoic swelling of the pancreatic head and body. ERCP revealed multiple stenosis of the intra-and extra-hepatic bile ducts, and diffuse irregular narrowing of the main pancreatic duct. The patient complained of thirst, and the minor salivary gland was examined histologically. Our diagnosis was Sjogren syndrome accompanied by sclerosing cholangitis and a pancreatic lesion. Obstructive jaundice also developed, and PTCD was therefore performed. Both the pancreatic swelling and multiple stenosis of the bile duct improved after steroids were administered. Case 2, a 71-year-old man, was admitted with jaundice. Abdominal ultrasonography showed hypoechoic swelling of the pancreas. ERCP showed stenosis of the common bile duct in the pancreatic head region and diffuse irregular narrowing of the main pancreatic duct. Histological examination of the minor salivary gland suggested Sjogren syndrome. Steroids were therefore administered because the presence of both hyper-gamma-globulinemia and positive antinuclear antibody suggested involvement of the autoimmune mechanism. Steroid therapy improved the jaundice as well as the findings from the cholangiograms and pancreatograms. We also encountered three similar cases, all consistent with the concept of autoimmune pancreatitis. The ultrasonographic findings of the pancreatic lesion (1) showed them as homogeneous and markedly hypoechoic areas and, (2) visualized the main pancreatic duct in the lesion, which facilitated a differential diagnosis of the neoplastic lesions. (3) Steroid therapy effectively decreased the hypoechoic area; in some cases, however, a hypoechoic area remained around the main pancreatic duct. PMID- 27277890 TI - Clinical Characteristics and Lesions Responsible for Swallowing Hesitation After Acute Cerebral Infarction. AB - Some stroke patients with a unilateral lesion demonstrate acute dysphagia characterized by a markedly prolonged swallowing time, making us think they are reluctant to swallow. In order to clarify the clinical characteristics and causative lesions of delayed swallowing, we conducted a retrospective analysis of 20 right-handed patients without a history of swallowing dysfunction who underwent videofluorography on suspicion of dysphagia after a first ischemic stroke. The oral processing time plus the postfaucial aggregation time required to swallow jelly for patients classified as having delayed swallowing was over 10 s. The time required for swallowing jelly was significantly longer than that without the hesitation (median value, 24.1 vs. 8.9 s, P < 0.001). The oral processing time plus the postfaucial aggregation time required for patients with delayed swallowing to swallow thickened water was largely over 5 s and significantly longer than that of patients without swallowing hesitation (median value, 10.2 vs. 3.3 s, P < 0.001). Swallowing hesitation caused by acute unilateral infarction could be separated into two different patterns. Because four of the five patients with a rippling tongue movement in the swallowing hesitation pattern had a lesion in the left primary motor cortex, which induces some kinds of apraxia, swallowing hesitation with a rippling tongue movement seems to be a representative characteristic of apraxia. The patients with swallowing hesitation with a temporary stasis of the tongue in this study tended to have broad lesions in the frontal lobe, especially in the middle frontal gyrus, which is thought to be involved in higher cognition. PMID- 27277891 TI - Stimulus-Dependent Inhibitor of Apoptosis Protein Expression Prolongs the Duration of B Cell Signalling. AB - Different dynamic behaviours of signalling activity can induce distinct biological responses in a variety of cells. However, the molecular mechanisms that determine the dynamics of kinase activities in immune cells are not well understood. In this study, we showed that the duration of both IkappaB kinase (IKK) and extracellular signal-regulated kinase (ERK) activities in B cell receptor (BCR)- and CD40-signalling pathways in B cells were regulated by transcriptional feedback loops. We conducted a time-course transcriptome analysis after BCR or CD40 stimulation and identified the following four candidate genes as feedback regulators for IKK and ERK: inhibitor of apoptosis protein (IAP), TNF alpha-induced protein 3, dual-specificity phosphatase 5, and sprouty homolog 2. Quantitative experiments and mathematical modelling suggested that IAP inhibition shortened the duration of IKK and ERK activity following both BCR and CD40 pathway stimulation, indicating a positive role for IAP in B cell signalling. Furthermore, transient kinase activities induced by IAP blockage reduced the levels of delayed expression genes. Together, our findings suggest that IKK and ERK activity durations can be fine-tuned by the coordinated regulation of positive and negative transcriptional feedback and that these network properties determine the biological output of B cells. PMID- 27277892 TI - Distress vocalization sequences broadcasted by bats carry redundant information. AB - Distress vocalizations (also known as alarm or screams) are an important component of the vocal repertoire of a number of animal species, including bats, humans, monkeys and birds, among others. Although the behavioral relevance of distress vocalizations is undeniable, at present, little is known about the rules that govern vocalization production when in alarmful situations. In this article, we show that when distressed, bats of the species Carollia perspicillata produce repetitive vocalization sequences in which consecutive syllables are likely to be similar to one another regarding their physical attributes. The uttered distress syllables are broadband (12-73 kHz) with most of their energy focussing at 23 kHz. Distress syllables are short (~4 ms), their average sound pressure level is close to 70 dB SPL, and they are produced at high repetition rates (every 14 ms). We discuss that, because of their physical attributes, bat distress vocalizations could serve a dual purpose: (1) advertising threatful situations to conspecifics, and (2) informing the threatener that the bats are ready to defend themselves. We also discuss possible advantages of advertising danger/discomfort using repetitive utterances, a calling strategy that appears to be ubiquitous across the animal kingdom. PMID- 27277893 TI - Cross Mapping Between the Priority Nursing Care for Stroke Patients Treated With Thrombolytic Therapy and the Nursing Interventions Classification (NIC). AB - OBJECTIVE: To verify the correspondence between the priority nursing care for stroke patients treated with thrombolytic therapy and the Nursing Interventions Classification (NIC). METHODS: A cross-mapping study with a semi-structured interview was conducted with 11 expert nurses who described priority nursing care in clinical practice, and mapped it to the NIC. RESULTS: Eleven nursing care priorities cited by the nurses were mapped to eight NICs, including Thrombolytic Therapy Management (4270). CONCLUSIONS: There was correspondence between all priority nursing care interventions for stroke patients treated with thrombolytic therapy and the NIC. IMPLICATIONS FOR NURSING PRACTICE: The nursing care cited by the nurses was corroborated by the NIC, providing evidence for the clinical practice. OBJETIVO: Verificar a correspondencia entre os cuidados de enfermagem prioritarios a pacientes com acidente vascular encefalico tratados com terapia trombolitica e a Classificacao das Intervencoes de Enfermagem (NIC). METODOS: Estudo de mapeamento cruzado com uma entrevista semi-estruturada aplicada a 11 enfermeiros especialistas que descreveram os cuidados de enfermagem prioritarios na pratica clinica, e mapeados para a NIC. RESULTADOS: Onze cuidados de enfermagem prioritarios foram citados pelos enfermeiros e mapeados em oito intervencoes de enfermagem NIC, incluindo a Thrombolytic Therapy Management (4270). CONCLUSOES: Houve correspondencia entre todos os cuidados de enfermagem prioritarios para pacientes com acidente vascular encefalico tratados com a terapia trombolitica e as intervencaes de enfermagem NIC. IMPLICACOES PARA A PRATICA DE ENFERMAGEM: Os cuidados de enfermagem citados pelos enfermeiros foram corroborados pela NIC, produzindo evidencias para a pratica clinica. PMID- 27277894 TI - Physical activity in European adolescents and associations with anxiety, depression and well-being. AB - In this cross-sectional study, physical activity, sport participation and associations with well-being, anxiety and depressive symptoms were examined in a large representative sample of European adolescents. A school-based survey was completed by 11,110 adolescents from ten European countries who took part in the SEYLE (Saving and Empowering Young Lives in Europe) study. The questionnaire included items assessing physical activity, sport participation and validated instruments assessing well-being (WHO-5), depressive symptoms (BDI-II) and anxiety (SAS). Multi-level mixed effects linear regression was used to examine associations between physical activity/sport participation and mental health measures. A minority of the sample (17.9 % of boys and 10.7 % of girls; p < 0.0005) reported sufficient activity based on WHO guidelines (60 min + daily). The mean number of days of at least 60 min of moderate-to-vigorous activity in the past 2 weeks was 7.5 +/- 4.4 among boys and 5.9 days +/- 4.3 among girls. Frequency of activity was positively correlated with well-being and negatively correlated with both anxiety and depressive symptoms, up to a threshold of moderate frequency of activity. In a multi-level mixed effects model more frequent physical activity and participation in sport were both found to independently contribute to greater well-being and lower levels of anxiety and depressive symptoms in both sexes. Increasing activity levels and sports participation among the least active young people should be a target of community and school-based interventions to promote well-being. There does not appear to be an additional benefit to mental health associated with meeting the WHO recommended levels of activity. PMID- 27277895 TI - Learning the landscape: implementation challenges of primary care innovators around cancer survivorship care. AB - PURPOSE: This study describes the experiences of early implementers of primary care-focused cancer survivorship delivery models. METHODS: Snowball sampling was used to identify innovators. Twelve participants (five cancer survivorship primary care innovators and seven content experts) attended a working conference focused on cancer survivorship population strategies and primary care transformation. Data included meeting discussion transcripts/field notes, transcribed in-depth innovator interviews, and innovators' summaries of care models. We used a multistep immersion/crystallization analytic approach, guided by a primary care organizational change model. RESULTS: Innovative practice models included: (1) a consultative model in a primary care setting; (2) a primary care physician (PCP)-led, blended consultative/panel-based model in an oncology setting; (3) an oncology nurse navigator in a primary care practice; and (4) two subspecialty models where PCPs in a general medical practice dedicated part of their patient panel to cancer survivors. Implementation challenges included (1) lack of key stakeholder buy-in; (2) practice resources allocated to competing (non-survivorship) change efforts; and (3) competition with higher priority initiatives incentivized by payers. CONCLUSIONS: Cancer survivorship delivery models are potentially feasible in primary care; however, significant barriers to widespread implementation exist. Implementation efforts would benefit from increasing the awareness and potential value-add of primary care-focused strategies to address survivors' needs. IMPLICATIONS FOR CANCER SURVIVORS: Current models of primary care-based cancer survivorship care may not be sustainable. Innovative strategies to provide quality care to this growing population of survivors need to be developed and integrated into primary care settings. PMID- 27277897 TI - An institutional approach to the management of the 'Can't Intubate, Can't Oxygenate' emergency in children. AB - The 'Can't Intubate Can't Oxygenate' emergency is rare in children. Nevertheless, airway clinicians involved in pediatric airway management must be able to rescue the airway percutaneously through the front of the neck should this situation be encountered. Little evidence exists in children to guide rescue techniques, and extrapolation of adult evidence may be problematic due to anatomical differences. This document reviews the currently available evidence, and presents a practical approach to standardizing equipment, techniques, and training for managing the 'Can't Intubate Can't Oxygenate' emergency in children. PMID- 27277896 TI - Cancer survivors' experiences with insurance, finances, and employment: results from a multisite study. AB - BACKGROUND: Cancer has significant implications on survivors' insurance coverage, financial status, and employment. We aimed to examine how these outcomes vary for survivors of different cancer types. METHODS: Using the Cancer Survivorship Supplement of the Medical Expenditures Panel Survey (MEPS), in 2013, we surveyed survivors of five common cancers who were diagnosed during 2003-2008 and were continuously enrolled in one of three health plans in Massachusetts, Colorado, and Washington State. RESULTS: Among 615 eligible respondents, 96 % reported having health insurance at the time of or since diagnosis; of those, few reported barriers in coverage to visit doctors or facilities of their choice. Approximately 15 % reported experiencing financial hardships due to cancer. Of the 334 who responded as having been employed at the time of or since diagnosis, approximately 25 % reported that they or their spouses remained at their jobs due to concerns about losing medical insurance. Further, 63 % reported making changes in their jobs or careers (e.g., took extended time off, worked part time, or declined promotion) due to cancer, and 42 % reported that cancer interfered with their physical and/or mental tasks at work or reduced productivity. Negative employment and financial implications were most common among those with lung, breast, and colorectal cancer, and those diagnosed before age 65. CONCLUSIONS: In this insured population, few experienced restrictions in cancer care coverage, though maintaining health insurance often drove employment decisions. Significant negative effects on finances and employment were observed among specific cancer types and younger survivors. IMPLICATIONS FOR CANCER SURVIVORS: Our study findings emphasize a need to identify ways of supporting survivors and provide tailored resources to reduce the untoward financial and work-related implications of cancer. PMID- 27277898 TI - Postmortem serum levels of total IgE. AB - The first aim of this study was to assess whether non-allergic deaths in non atopic individuals with increasing postmortem intervals are characterized by progressively greater concentrations of total IgE in postmortem serum from femoral blood. Our second goal was to determine whether traumatic deaths with different survival times, septic deaths, and deaths in individuals suffering from diseases with significant systemic inflammation are systematically characterized by increased concentrations of total IgE in postmortem serum from femoral blood. Four study groups were prospectively and retrospectively formed (non-allergic deaths in non-atopic individuals with increasing postmortem intervals, traumatic deaths in non-atopic individuals with different survival times, deaths possibly related to sepsis in non-atopic individuals, and deaths occurring in non-atopic individuals with disseminated malignancies at autopsy). Unenhanced computed tomography, autopsy, histology, and biochemistry were performed in all cases. First results indicate that increasing postmortem intervals are not associated with progressively increasing postmortem serum IgE levels. Moreover, the obtained results do not reveal that severe trauma, bacterial sepsis, and disseminated malignancies are systematically associated with increased postmortem serum IgE levels, irrespective of survival time duration. Though the usefulness of increased total IgE concentrations in postmortem samples to assess any underlying atopic disposition or death preceded by acute IgE-mediated allergic reaction remains questionable, measurements of total IgE are possible in postmortem serum samples. PMID- 27277899 TI - Computer-Assisted In Sensu Exposure for Posttraumatic Stress Disorder: Development and Evaluation. AB - BACKGROUND: Dissociative states during psychotherapy sessions reduce the benefit of exposure-based therapy for posttraumatic stress disorder (PTSD). Thus, in evidence-based therapeutic programs such as dialectical behavior therapy for PTSD (DBT-PTSD), therapists apply specific antidissociative skills to reduce dissociative features during in sensu exposure. In addition to therapist-guided sessions, exposure protocols often require that the patients listen to audio recordings of exposure sessions in self-management. The problem of how to prevent dissociative features during such self-administered exposure exercises has not been resolved yet. Hence, we developed the computer program MORPHEUS that supports the application of self-administered exposure exercises. MORPHEUS continuously monitors the level of dissociative states and offers state-related antidissociative skills. OBJECTIVE: This study sought to examine the acceptance and feasibility of the MORPHEUS program. METHODS: Patients who underwent 12 weeks of residential DBT-PTSD treatment used MORPHEUS during exposure exercises in self management. After the treatment, they filled out evaluation questionnaires. RESULTS: In sum, 26 patients receiving a 12-week standard DBT-PTSD program participated in this study; 2 participants could not be analyzed because of missing data. All the patients used MORPHEUS as often as it was required according to the DBT-PTSD treatment (2 to 5 times a week). The overall acceptance and feasibility as rated by the patients was high: for example, patients found the skills useful to block dissociation (mean 4.24 on a scale from 0 to 5, SD 0.24) and stated that they would use the program again (mean 4.72 on a scale from 0 to 5, SD 0.11). Furthermore, patients indicated that they would recommend MORPHEUS to a friend (mean 4.44 on a scale from 0 to 5, SD 0.12). In 82% (32/39) of the cases, the use of antidissociative skills was related to a decrease in dissociation. In 18% (5/39), dissociation remained unchanged or increased. CONCLUSIONS: The evaluative data suggest high acceptability and feasibility of MORPHEUS. Further studies should evaluate the effectiveness of the skills applied during the program. TRIAL REGISTRATION: World Health Organization International Clinical Trials Registry Platform: DRKS00006226; http://apps.who.int/trialsearch/Trial2.aspx?TrialID= DRKS00006226 (Archived by WebCite at http://www.webcitation.org/ 6hxuFbIUr). PMID- 27277900 TI - STAP cells. PMID- 27277902 TI - An improved balloon snake for HIFU image-guided system. AB - Target segmentation in ultrasound images is a key step in the definition of the intro-operative planning of high-intensity focused ultrasound therapy. This paper presents an improvement for the balloon snake in segmentation. A sign function, designed by the edge map and the moving snake, is added to give the direction of the balloon force on the moving snake separately. Segmentation results are demonstrated on ultrasound images and the effectiveness and convenience shown in applications. PMID- 27277901 TI - New developments in paediatric cardiac functional ultrasound imaging. AB - Ultrasound imaging can be used to estimate the morphology as well as the motion and deformation of tissues. If the interrogated tissue is actively deforming, this deformation is directly related to its function and quantification of this deformation is normally referred as 'strain imaging'. Tissue can also be deformed by applying an internal or external force and the resulting, induced deformation is a function of the mechanical tissue characteristics. In combination with the load applied, these strain maps can be used to estimate or reconstruct the mechanical properties of tissue. This technique was named 'elastography' by Ophir et al. in 1991. Elastography can be used for atherosclerotic plaque characterisation, while the contractility of the heart or skeletal muscles can be assessed with strain imaging. Rather than using the conventional video format (DICOM) image information, radio frequency (RF)-based ultrasound methods enable estimation of the deformation at higher resolution and with higher precision than commercial methods using Doppler (tissue Doppler imaging) or video image data (2D speckle tracking methods). However, the improvement in accuracy is mainly achieved when measuring strain along the ultrasound beam direction, so it has to be considered a 1D technique. Recently, this method has been extended to multiple directions and precision further improved by using spatial compounding of data acquired at multiple beam steered angles. Using similar techniques, the blood velocity and flow can be determined. RF-based techniques are also beneficial for automated segmentation of the ventricular cavities. In this paper, new developments in different techniques of quantifying cardiac function by strain imaging, automated segmentation, and methods of performing blood flow imaging are reviewed and their application in paediatric cardiology is discussed. PMID- 27277903 TI - Prolonged vortex formation during the ejection period in the left ventricle with low ejection fraction: a study by vector flow mapping. AB - PURPOSE: Vortex formation in the left ventricle (LV) can be visualized by novel vector flow mapping (VFM) based on color Doppler and speckle tracking data. The aim of this study was to evaluate the impact of a vortex during the ejection period using VFM. SUBJECTS AND METHODS: Color Doppler images were obtained to produce VFM images in 80 subjects (20 normal, 29 with dilated cardiomyopathy, and 31 with old myocardial infarction). The duration of the LV vortex was measured and expressed as the ratio to the ejection time (VTRe). RESULTS: The VTRe showed significant correlations with EDV (rho = 0.672, p < 0.001), ESV (rho = 0.772, p < 0.001), EF (rho = -0.783, p < 0.001), left atrium diameter (LAd) (rho = 0.302, p = 0.007), stroke volume (rho = -0.600, p < 0.001), e' (rho = -0.389, p < 0.001), a' (rho = -0.314, p = 0.005), s' (rho = -0.512, p < 0.001), and E/e' (rho = 0.330, p = 0.003). The diastolic parameters (e', a', E/e', LAd) were not correlated when they were adjusted by EF. CONCLUSIONS: In the normal LV, a vortex existed for only a limited time during the early ejection period. In contrast, the lower the EF was, the longer the vortex remained during systole. Evaluation of vortices by VFM may noninvasively provide novel insights into the pathophysiology of impaired cardiac function. PMID- 27277904 TI - Serial change of liver stiffness measured by acoustic radiation force impulse imaging in chronic liver disease: correlation with biochemical markers. AB - PURPOSE: In patients with chronic diffuse liver diseases, liver fibrosis severity is an important element for prognosis and for selecting therapy. Acoustic radiation force impulse (ARFI) imaging techniques were recently developed to measure liver fibrosis, but their specificity is impaired by cholestasis, inflammation, or edema in acute hepatitis. Herein, our objectives were to evaluate serial changes in shear wave velocity (SWV) and to correlate these changes with biochemical activity. METHODS: This study included 108 patients who underwent ARFI because of viral hepatitis [hepatitis B (HBV) or C (HCV)] with serial follow-up after 3-6 months at our institution between August 2011 and May 2013. Based on baseline and follow-up ARFI, we divided patients with HBV and HCV into two groups: a decreasing SWV group and a non-decreasing SWV group. We evaluated serial SWV changes and correlated these changes with biochemical activity changes. RESULTS: The patients were divided into SWV groups as follows: decreasing SWV group (HBV, n = 23; HCV, n = 7) and non-decreasing SWV group (HBV, n = 40; HCV, n = 38). In both HBV and HVC patients, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly decreased at follow up in the decreasing SWV group. CONCLUSIONS: The liver stiffness value assessed by ARFI became lower over time in patients who had decreasing AST and ALT levels. According to this study, ARFI overestimates fibrosis grade in patients with high AST and ALT. Thus, assessment of liver fibrosis by ARFI elastography should include consideration of biochemical markers such as AST and ALT levels and additional follow-up using ARFI elastography. PMID- 27277905 TI - Use of strain ratio in evaluating superficial soft tissue tumors on ultrasonic elastography. AB - OBJECT: The aim of this study was to describe the strain ratio in histopathologically confirmed superficial soft tissue tumors using ultrasonic elastography (USE). METHODS: From March to August 2012, 94 soft tissue tumors in 79 consecutive patients (age range 19-70 years) were examined using USE for palpable masses. Among them, 39 lesions in 36 patients were histopathologically confirmed. Thirty-four lesions in 31 patients with lipoma, ganglion, epidermal inclusion cyst, and pilomatricoma were included: 34 histopathologically confirmed mature lipomas (n = 19), ganglia (n = 6), epidermal inclusion cysts (n = 5), and pilomatricomas (n = 4). Ultrasonographic features of margins, echogenicity, walls, ultrasonic transmission, and vascular flow via Doppler ultrasonography were evaluated. The strain ratios were calculated from the USE strain measured within the lesion and in adjacent tissue. Intraclass correlation (ICC) with Cohen's kappa was used to determine intraobserver agreement, and the strain ratios of the three groups were compared using Mann-Whitney U tests. All statistical analyses were performed using R package statistical software, and p values <0.05 were considered to be statistically significant. RESULTS: On USE, repeated measurements of the strain ratios showed excellent intraobserver agreement [ICC value = 0.952 (CI 0.905-0.977), p < 0.05]. The strain ratios of lipomas (median +/- standard error 0.83 +/- 0.18) were statistically different (p < 0.05) from those of ganglia, epidermal inclusion cysts, and pilomatricomas. The strain ratios of ganglia (2.78 +/- 0.48) were also statistically different (p < 0.05) from those of epidermal inclusion cysts and pilomatricomas. The strain ratios of epidermal inclusion cysts (0.17 +/- 0.21) were not statistically different (p > 0.05) from that of pilomatricomas (0.13 +/- 0.02). CONCLUSION: Strain ratios determined by USE help to differentiate lipomas and ganglia from other superficial soft tissue tumors. Our results suggest that USE could be used in addition to traditional ultrasound techniques to obtain diagnostic clues in the evaluation of superficial soft tissue tumors. PMID- 27277906 TI - Reproducibility of two different methods for performing mean gray value evaluation of cyst content in endometriomas using VOCAL. AB - OBJECTIVE: To compare two different methods (manual sampling of the entire cyst and semi-automated spherical sampling from the central part of the cyst) for calculating the mean gray value (MGV) from the cystic content in endometriomas using virtual organ computer-aided analysis (VOCAL). METHODS: Forty-one volumes from histologically confirmed endometriomas were retrieved from our database and the volumes were analyzed to compare the MGVs obtained via the two modalities. In addition, to evaluate the reproducibility in a sample of 20 volumes, two different observers calculated the MGV from cyst content using VOCAL software. For each method, each examiner analyzed the volumes twice, 3 weeks apart, for assessment of intra-observer agreement. First, manual sampling of the internal contour of all the cysts was performed, and 1 week later semi-automated 2-cm sphere sampling from the central part of the cyst was carried out. In addition, the observers recorded the time spent performing each analysis. Inter- and intra observer reproducibility was evaluated for each method using intra-class correlation coefficients (ICC). RESULTS: There was no difference in the mean MGV between manual sampling (22.211 +/- 7.541) and the semi-automated modality of sampling (23.840 +/- 8.621, p = 0.439). The correlation between manual and semi automated sampling measurement was high (r = 0.92). According to the ICCs, there was no significant difference in interobserver reliability between manual sampling (0.931; 95 % CI, 0.824-0.973) and the semi-automated modality of sampling (0.924; 95 % CI, 0.809-0.970). Intra-observer reproducibility for both examiners was good (ICC > 0.94). Semi-automated measurements were obtained faster than those obtained by manual evaluation (p = 0.0001 for observer 1 and p = 0.083 for observer 2). CONCLUSIONS: Both methods seem to be reliable, but the semi automated method using the sphere should be preferred because it is a less time consuming procedure. PMID- 27277907 TI - Low-frequency high-definition power Doppler in visualizing and defining fetal pulmonary venous connections. AB - PURPOSE: The use of low-frequency high-definition power Doppler in assessing and defining pulmonary venous connections was investigated. METHODS: Study A included 260 fetuses at gestational ages ranging from 18 to 36 weeks. Pulmonary veins were assessed by performing two-dimensional B-mode imaging, color Doppler flow imaging (CDFI), and low-frequency high-definition power Doppler. A score of 1 was assigned if one pulmonary vein was visualized, 2 if two pulmonary veins were visualized, 3 if three pulmonary veins were visualized, and 4 if four pulmonary veins were visualized. The detection rate between Exam-1 and Exam-2 (intra observer variability) and between Exam-1 and Exam-3 (inter-observer variability) was compared. In study B, five cases with abnormal pulmonary venous connection were diagnosed and compared to their anatomical examination. RESULTS: In study A, there was a significant difference between CDFI and low-frequency high-definition power Doppler for the four pulmonary veins observed (P < 0.05). The detection rate of each pulmonary vein when employing low-frequency high-definition power Doppler was higher than that when employing two-dimensional B-mode imaging or CDFI. There was no significant difference between the intra- and inter-observer variabilities using low-frequency high-definition power Doppler display of pulmonary veins (P > 0.05). The coefficient correlation between Exam-1 and Exam-2 was 0.844, and the coefficient correlation between Exam-1 and Exam-3 was 0.821. In study B, one case of total anomalous pulmonary venous return and four cases of partial anomalous pulmonary venous return were diagnosed by low-frequency high definition power Doppler and confirmed by autopsy. CONCLUSIONS: The assessment of pulmonary venous connections by low-frequency high-definition power Doppler is advantageous. Pulmonary venous anatomy can and should be monitored during fetal heart examination. PMID- 27277908 TI - HDlive imaging of the face of fetuses with autosomal trisomies. AB - BACKGROUND: Our objective is to present our experience of facial dysmorphism reconstructed employing conventional three-dimensional (3D) ultrasound and HDlive in fetuses with autosomal trisomies. METHODS: Seven fetuses with autosomal trisomies (one case of trisomy 13, three of trisomy 18, and three of trisomy 21) at 16-38 weeks' gestation were studied using 3D ultrasound and HDlive. RESULTS: In one case of trisomy 21 at 29 weeks and 5 days, upward slanting eyes, a flattened nose, low-set ears, and the corners of the mouth turned down were noted employing HDlive. In the other two cases of trisomy 21, both techniques showed the same facial findings. In one case of trisomy 18 at 27 weeks and 6 days, a small head accompanied by a prominent back portion of the head, low-set ears, a small jaw, upturned nose, narrow eyelid folds, and widely spaced eyes were identified using HDlive. In the other two cases of trisomy 18, HDlive showed more detailed features of the fetal face compared to conventional 3D ultrasound. In the single case of trisomy 13 at 31 weeks and 1 day, cleft lip and close-set eyes were recognized with both 3D ultrasound and HDlive. CONCLUSION: HDlive can provide clearer facial images than conventional 3D ultrasound. In particular, HDlive is superior to conventional 3D ultrasound for the depiction of eye fissures because of its shadowing effect. HDlive may be a useful diagnostic modality for the antenatal evaluation of subtle fetal facial dysmorphism. PMID- 27277910 TI - Evaluation of common carotid artery changes in Saudi current smokers using medical ultrasound (B-mode and Doppler). AB - PURPOSE: This study evaluates using ultrasound the changes that occur in wall thickness, blood flow velocity, and Doppler indices of the common carotid arteries (CCAs) in healthy Saudi adult males who are current smokers. METHODS: A prospective study was performed between May 2011 and May 2013 with a group consisting of nonsmokers (n = 180; 36 %) and current smokers (n = 320; 64 %) with a mean age of 25 +/- 2.6 years. In all cases, the CCA ultrasound scanning protocol met the standards established by the American Institute of Ultrasound in Medicine (AIUM) to measure intima media thickness (IMT), peak systolic velocity (PSV), and end diastolic velocity (EDV). The Statistical Package for the Social Sciences (SPSS) was used to analyze the results. RESULTS: Significant linear and positive correlations were noted between the level of daily consumption of cigarettes smoked and carotid mean IMT, PSV, and Doppler indices, while a linear and negative correlation was present between cigarette smoking and mean EDV. These findings were significant when compared with the results for nonsmokers. CONCLUSIONS: Cigarette smoking is associated with CCA morphological changes caused by significant impairment of arterial endothelial function, and an increase in daily cigarette consumption significantly leads to a decrease in the blood flow velocity of CCAs. PMID- 27277909 TI - Quantification of sonographic echogenicity by the gray-level histogram in patients with supraspinatus tendinopathy. AB - PURPOSE: The aim of this study was to compare the gray-level value of the supraspinatus tendon of a painful shoulder with that of a normal shoulder measured by ultrasonography, and to investigate whether a low mean gray-level value of the supraspinatus tendon could indicate a partial-thickness or incomplete full-thickness tear. METHODS: Two hundred and ten patients had significant unilateral shoulder pain with the clinical suspicion of rotator cuff tendinopathy. They underwent bilateral shoulder ultrasonography, and the mean echogenicity of the histogram was calculated on the screen. The mean gray-level value of each patient's contralateral asymptomatic shoulder was compared with that of the painful shoulder. RESULTS: Based on the scan of transverse and longitudinal planes, a significant difference existed between the symptomatic shoulder and contralateral asymptomatic shoulder (p < 0.0001). The mean gray level values of symptomatic shoulders showed no statistically significant difference between the patients who underwent surgery and the patients who underwent conservative treatment. CONCLUSIONS: We demonstrated that the ultrasound gray-level histogram is a promising tool for detecting the hypoechogenic appearance of supraspinatus tendinopathy. A decrease in the mean gray-level value on the symptomatic shoulder may be used as an alternative sonographic indicator of rotator cuff partial-thickness tear or tendinopathy. LEVEL OF EVIDENCE: Diagnostic level III. PMID- 27277911 TI - Real-time tissue elastography assessment of skin and subcutaneous tissue strains in legs with lymphedema. AB - PURPOSE: To confirm the feasibility of assessing strains of the skin and subcutaneous tissue in normal legs and legs with lymphedema via free-hand real time tissue elastography (RTE) using a phantom. METHODS: After placing a phantom on the skin, we measured the strains of the phantom (S p), skin (S sk), and subcutaneous tissue (S sc) of the inner thigh and calf by free-hand RTE in 35 healthy volunteers. A reference S p was set using these data. We then assessed S sk and S sc in each leg of 15 patients with unilateral stage II lymphedema. RESULTS: In the healthy volunteers, the strain was largest in the subcutaneous tissue of the thigh, followed by the subcutaneous tissue of the calf, skin of the thigh, and skin of the calf. These differences were each significant. In the patients with unilateral lymphedema, S sk and S sc in the thigh and calf were not different between the affected and unaffected legs. CONCLUSION: It was feasible to assess the strains of the skin and subcutaneous tissue using free-hand RTE and standardization of the compression force using a phantom. We failed to demonstrate decreased strains of the skin and subcutaneous tissue in legs with stage II lymphedema compared with healthy legs. PMID- 27277912 TI - Ultrasonography is convenient and useful for assessment and follow-up of Takayasu's arteritis. AB - A 20-year-old woman first came to our hospital complaining of high fever and pain affecting the whole body. Takayasu's arteritis (TA) was diagnosed. Following full body examination, many vessels between the bilateral neck and iliac arteries were found to be impaired. Ultrasonography (US) showed the characteristic wall thickening of TA in the left common carotid artery. After starting prednisolone treatment (40 mg/day), symptoms improved quickly and vessel walls gradually became thinner. However, chest pain recurred when prednisolone was tapered to 20 mg/day. Blood tests showed no signs of recurring inflammation, and US revealed worsened wall thickening only in the left carotid artery. We therefore diagnosed local recurrence of activation of TA. Assessing local recurrence of TA with a blood test is difficult, particularly after prescribing steroids. In this case, US identified the local changes attributable to TA before any other diagnostic modality. US can be useful in assessing inflammation and offers a good strategic tool for initial diagnosis of TA. PMID- 27277913 TI - Chronological changes in the ultrasonic findings of gallbladder metastasis from renal cell carcinoma: a case report and review. AB - The present case involves a gallbladder metastasis from renal cell carcinoma (GBMRCC). During 11 months of ultrasound follow-up examinations, the mass, covered with a highly echoic surface layer, exhibited the following changes: the wide base became constricted, the tumor surface became irregular, and the mass increased in diameter. A histopathological examination confirmed that the tumor cells were mainly present in the subepithelial layer, the gallbladder epithelium had ruptured, and necrotic debris covered the tumor surface. The highly echoic surface layer observed on the latest ultrasound images corresponded to the necrotic debris. These findings suggested that GBMRCCs initially develop in the subepithelial layer and then undergo expansive intraluminal growth. They subsequently cause the epithelium to rupture, resulting in necrotic debris appearing on the tumor surface. PMID- 27277914 TI - Multiple comet tail artifacts in the liver: a case of congenital hepatic fibrosis showing unusual biliary appearance. AB - Congenital hepatic fibrosis (CHF) is a form of autosomal recessive polycystic kidney disease. Because of the common underlying pathophysiology of ductal plate malformation, CHF can be accompanied by an abnormal biliary appearance, which is characterized by a saccular or fusiform dilatation of the bile ducts. We encountered the case of a 35-year-old man suffering from CHF concomitant with esophageal varices, which were treated by endoscopic sclerotherapy. The patient had elevated serum concentrations of alkaline phosphatase and gamma-glutamyl transpeptidase without apparent biliary disease, including hepatolithiasis or a history of cholangitis. Magnetic resonance cholangiography showed an abnormal biliary appearance, which was not saccular or fusiform but had multiple stenosis with unknown causes. B-mode sonogram showed multiple comet tail artifacts in the liver parenchyma, probably corresponding to the compact fibrosis bands and bile in the bile duct as well as peripheral bile duct dilatation, which was proven pathologically. We propose that multiple comet tail artifacts in the liver may suggest the presence of a bile duct abnormality in patients with CHF, suggesting the potential risk for developing biliary complications. PMID- 27277915 TI - Non-radiation endoscopic removal of common bile duct stone assisted with abdominal ultrasonography in a pregnant patient. AB - A common bile duct stone was detected in a pregnant patient who was in her second trimester. Avoiding the use of fluoroscopy, abdominal ultrasonography-assisted endoscopic removal of the stone was successful. PMID- 27277916 TI - Glomus tumor of a female breast: a case report and review of the literature. AB - Glomus tumor is a benign, subcutaneous neoplasm which usually arises in areas that are rich in glomus bodies, most commonly the digital area, and usually appears as a painful nodule. Glomus tumor of the breast is extremely rare, and there has been only limited information reported in the literature to date. We herein present a case of a glomus tumor arising from the breast, showing a well circumscribed, hypervascular, solid and hypoechoic tumor within the retromammary fat. The tumor was resected and the patient's pain was relieved immediately after the surgery. She remains well without any symptoms after a year. This report describes a unique case of this type of tumor. PMID- 27277917 TI - Usefulness of contrast-enhanced ultrasonography for intracystic breast tumors: a report of three cases. AB - Cystic breast lesions are caused by a wide spectrum of breast diseases and can range from simple cysts to malignant tumors. Ultrasonography is a good tool for evaluation of the morphology and vascularity of cystic breast lesions. We report three patients in whom contrast-enhanced ultrasonography (CEUS) was used to evaluate intracystic tumors. One of the three patients was diagnosed with intracystic papilloma. Compared with conventional ultrasonography alone, CEUS more clearly demonstrated that the solid component within the mass was lobulated with a narrow base. The other two patients were diagnosed with intracystic papillary carcinoma, and CEUS clearly revealed the presence of widely elevated solid components within both masses, suggesting malignancy. Therefore, CEUS simplified morphological evaluation by enhancing the solid components within the cystic masses. PMID- 27277918 TI - Fetal stomach paracentesis in combined duodenal and esophageal atresia. AB - Fetuses with concomitant duodenal atresia (DA) and esophageal atresia (EA) might develop in utero gastric rupture as well as neonatal respiratory complication due to dilated stomach and duodenum. Our patient with the typical "double bubble" appearance was highly suspected to have DA in the second trimester. Follow-up examinations revealed a massively dilated stomach and duodenum with a dilated distal esophagus, indicating concomitant DA and EA. With advancing pregnancy, the fetal abdomen progressively increased in size by retention of fluid in the closed loop of DA and EA. To avoid gastric perforation, prenatal stomach paracentesis using an ultrasound-guided needle was performed three times until delivery. A male neonate born at 37 weeks gestation showed no respiratory complication. Perinatal clinical features and operative findings revealed combined DA and EA (gross type A). He was successfully managed with duodenoduodenostomy, followed by esophago-esophagostomy. On fetal sonography, the marked "double bubble" appearance and the cystic structure presenting peristalsis-like movement above the diaphragm were indicative of concomitant DA and EA. Fetal stomach paracentesis could contribute to the improvement of perinatal outcomes in fetuses with this pathological condition. PMID- 27277919 TI - HDlive 3D ultrasound and follicular development. AB - Two-dimensional (2D) ultrasonography is the fundamental technology on which diagnosis, management, and control in reproductive medicine depends. Over the years there have been efforts to improve 2D ultrasound image quality. In recent years, a series of software has appeared that has generated enormous interest. The goal of these modes has been to improve image quality and diagnostic accuracy. HDlive incorporates a movable virtual adjustable light source which, as it penetrates, produces selective illumination with respective shadows that result from the structures where light is reflected. This combination of light and shadow results in spectacular images which appear much more real than those obtained with conventional 3D ultrasonography. PMID- 27277920 TI - Valsalva test: a new method to evaluate postpartum anal sphincter function by perineal ultrasound. PMID- 27277922 TI - What is coronary blood flow reserve? Insights using myocardial contrast echocardiography. AB - This review will briefly describe the principles of myocardial contrast echocardiography, and then discuss the clinical and experimental observations that led to the use of this approach to investigate the pathophysiological basis of coronary blood flow reserve. The insights offered by myocardial contrast echocardiography are unique and novel, and highlight the importance of the myocardial capillaries in determining coronary blood flow reserve in health and disease. PMID- 27277921 TI - 'Bringing respite in the burden of illness' - dog handlers' experience of visiting older persons with dementia together with a therapy dog. AB - AIMS AND OBJECTIVES: To illuminate meanings of the lived experiences of dog handlers' when visiting older persons with dementia with their therapy dog. BACKGROUND: Studies indicate that care of persons with dementia should focus on a person-centred approach with the person's interests in the centre. Animal assisted therapy using a therapy dog in the care of persons with dementia has been shown to increase well-being and decrease problematic behaviours associated with the illness. DESIGN: A qualitative lifeworld approach was adopted for this study. METHODS: Data were collected from open-ended interviews with nine dog handlers, and the analysis conducted using the phenomenological hermeneutical method. RESULTS: The structural analysis resulted in one theme, 'Respite from the burden of illness for persons with dementia'. CONCLUSIONS: Visiting a person with dementia can be seen as an act of caring, providing temporary respite from their illness, and creating a special relationship between handler and patient. A therapy dog visit can represent a moment of communion between the handler and the person with dementia. IMPLICATION FOR CLINICAL PRACTICE: Dog handlers use their skills and knowledge to promote a situation that reduces symptoms of illness and encourages healthier behaviour. The results of this study may be of interest to researchers, clinical practitioners, caregivers and dog handlers who care for persons with dementia using therapy dog teams on prescription as an alternative method to minimise behavioural and psychological symptoms of dementia. PMID- 27277923 TI - Usefulness of real-time three-dimensional echocardiography in evaluating aortic root diameters during a cardiac cycle. AB - BACKGROUND: The preoperative evaluation of aortic root diameters is important for determining the surgical strategy in patients with aortic valve disease. The purpose of this study was to evaluate the usefulness of real-time three dimensional echocardiography (3D-echo) for the evaluation of aortic root diameters compared with two-dimensional echocardiography (2D-echo) and to evaluate aortic root dynamics. METHODS: We prospectively investigated 23 patients with aortic stenosis (AS) and 37 normal controls. With 2D-echo, aortic root diameters were measured from the parasternal long-axis view. With 3D-echo, long axis and short-axis views of the aortic root were reconstructed from the full volume image, and aortic root diameters were measured at mid-systole, end systole, mid-diastole, and end-diastole. These aortic root diameters were compared between 2D and 3D measurements, regarding intraoperative and computed tomographic measurements as the gold standard. In addition, dynamic changes of aortic root diameters during a cardiac cycle were evaluated. RESULTS: Aortic root diameters measured by 3D-echo were larger than those measured by 2D-echo (annular diameter 19.6 +/- 2.1 vs. 21.2 +/- 2.2 mm, p < 0.0001), and 3D measurements were closer to intraoperative and computed tomographic measurements than 2D measurements. The diameter of the aortic annulus increased during diastole, but the changes during a cardiac cycle were significantly smaller in patients with AS than in normal controls (2.0 +/- 2.2 vs. 7.8 +/- 3.4%, p < 0.0001). CONCLUSIONS: Aortic root diameters can be more accurately measured by 3D-echo than 2D-echo. Dynamic change of the aortic annulus during a cardiac cycle was smaller in patients with AS. 3D-echo is useful for the quantitative evaluation of the aortic root, including dynamics during a cardiac cycle. PMID- 27277924 TI - Time-dependent variation in coronary flow velocity reserve induced by adenosine triphosphate: comparison to low-dose dipyridamole. AB - BACKGROUND: Measuring the coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE) has been widely performed using adenosine. Although adenosine infusion is known to induce transient variation of hyperemia, the timing to measure the CFVR has not been well addressed. Therefore, we aimed to clarify the difference between the peak CFVR and at 2 min following adenosine triphosphate (ATP) infusion compared to the CFVR after low-dose dipyridamole infusion. METHODS AND RESULTS: A total of 26 patients with coronary artery diseases underwent TTDE. The coronary flow velocity (CFV) of the left anterior descending artery (LAD) was monitored during ATP infusion at 0.14 mg/kg/min. The CFVR was measured both at the first peak and at 2 min following ATP infusion, and after dipyridamole infusion at 0.56 mg/kg/min for 4 min. The first peak of hyperemia occurred 63.7 +/- 8 s after starting ATP infusion. The value of the peak CFVR was significantly higher than the CFVR at 2 min following ATP stress, which was equivalent to the CFVR after dipyridamole infusion (2.30 +/- 0.92, 1.83 +/- 0.77, and 1.70 +/- 0.68, respectively, P < 0.001). Applying a cut-off value of 2.0 to predict angiographic LAD stenosis, the CFVR at 2 min following ATP stress was significantly correlated to the angiographic findings. However, the peak CFVR after ATP infusion did not correlate with the angiographic findings. CONCLUSIONS: During ATP infusion, the peak CFVR was significantly higher than the CFVR at 2 min, which was equivalent to the CFVR after low-dose dipyridamole. This finding should be considered for the standardization of CFVR measurements. PMID- 27277925 TI - Aortic regurgitation caused by cusp bending of aortic valve leaflet. AB - Pure aortic regurgitation (AR) is caused by primary disease of the aortic leaflet and/or the aortic root. However, there are many patients with AR with unclear etiology and mechanism. The assessment of mechanism is critical to the decision of surgical modality for AR. Echocardiography, particularly a detailed analysis of the aortic leaflets and root by transesophageal echocardiography (TEE), could be an important diagnostic step to assess its mechanism. In this report, we present a case of AR in which the TEE images led to diagnosis of cusp bending of aortic leaflet without specific findings indicating this pathology. PMID- 27277926 TI - A patient came back with retrograde coronary flow in the distal right coronary artery 2 years after coronary intervention: clinical significance of retrograde coronary flow to detect coronary artery occlusion. AB - A 69-year-old male patient, who had a history of coronary stent implantation to the proximal right coronary artery (RCA), presented with exertional chest pain. Transthoracic Doppler echocardiography revealed retrograde coronary flow in the distal RCA, and treadmill stress echocardiography revealed inducible myocardial ischemia in the inferior and posterior segments. Coronary angiography demonstrated a severe stenotic lesion with flow delay in the mid RCA and collateral circulation to the distal RCA from the left coronary artery. Detection of retrograde coronary flow in the distal RCA using transthoracic Doppler echocardiography is a useful method to diagnose subtotal occlusion of the RCA. PMID- 27277927 TI - Stent placement in the ductus venosus of a neonate with total anomalous pulmonary venous return. AB - A newborn with right isomerism, infracardiac total anomalous pulmonary venous return (TAPVR), and obstruction of the ductus venosus underwent stent implantation in the ductus venosus at 4 h after birth. This procedure averted early pulmonary venous obstruction. Since gradual neointimal proliferation subsequently occurred within the stent, the patient underwent stent balloon dilatation at 35 days of age and underwent surgical repair of the TAPVR with a Blalock-Taussig shunt operation at 53 days of age. Finally, the patient was discharged without any complications. Transthoracic echocardiography is very useful to confirm subsequent minimal change within the stent. PMID- 27277928 TI - Mitral annuloplasty ring detachment in real-time three-dimensional echocardiography. PMID- 27277929 TI - Evidence for impaired left ventricular ejection in hypertrophic obstructive cardiomyopathy: dynamic aortic ejection flow velocity profile demonstrated by pulsed Doppler echocardiography. PMID- 27277930 TI - A case of transient myocardial dysfunction with electrocardiographic abnormality due to acute carbon monoxide poisoning. PMID- 27277931 TI - Impact of the right parasternal view with supine positioning for echocardiographic visualization of acute type A aortic dissection. PMID- 27277933 TI - Immunoanalysis for environmental monitoring and human health. PMID- 27277932 TI - Retinal ganglion cell topography and spatial resolving power in African megachiropterans: Influence of roosting microhabitat and foraging. AB - Megachiropteran bats (megabats) show remarkable diversity in microhabitat occupation and trophic specializations, but information on how vision relates to their behavioral ecology is scarce. Using stereology and retinal wholemounts, we measured the topographic distribution of retinal ganglion cells and determined the spatial resolution of eight African megachiropterans with distinct roosting and feeding ecologies. We found that species roosting in open microhabitats have a pronounced streak of high retinal ganglion cell density, whereas those favoring more enclosed microhabitats have a less pronounced streak (or its absence in Hypsignathus monstrosus). An exception is the cave-dwelling Rousettus aegyptiacus, which has a pronounced horizontal streak that potentially correlates with its occurrence in more open environments during foraging. In all species, we found a temporal area with maximum retinal ganglion cell density (~5,000-7,000 cells/mm2 ) that affords enhanced resolution in the frontal visual field. Our estimates of spatial resolution based on peak retinal ganglion cell density and eye size (~6-12 mm in axial length) range between ~2 and 4 cycles/degree. Species that occur in more enclosed microhabitats and feed on plant material have lower spatial resolution (~2 cycles/degree) compared with those that roost in open and semiopen areas (~3-3.8 cycles/degree). We suggest that the larger eye and concomitant higher spatial resolution (~4 cycles/degree) in H. monstrosus may have facilitated the carnivorous aspect of its diet. In conclusion, variations in the topographic organization and magnitude of retinal ganglion density reflect the specific ecological needs to detect food/predators and the structural complexity of the environments. J. Comp. Neurol. 525:186-203, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27277934 TI - Statin use and the risk of developing diabetes: a network meta-analysis. AB - PURPOSE: Randomized controlled trials have shown mixed findings regarding the association of statins and diabetes. This systematic literature review and network meta-analysis (NMA) was performed to update evidence on this association to possibly assist clinicians in making more informed treatment choices. METHODS: We identified studies relevant to our NMA by performing study searches in databases like Embase, Cochrane, and PubMed, published between August 2010 and June 2014. Pre-2010 studies were identified from bibliography of previously published meta-analyses. Unpublished study data were found from clinicaltrial.gov. Data synthesis was performed by pairwise meta-analysis and NMA within a Frequentist framework. RESULTS: Twenty nine trials in which 1 63 039 participants had been randomized were included in this review; among these 1 41 863 were non-diabetic patients. The direct meta-analysis showed that statins, as a class, significantly increased the likelihood of developing diabetes by 12% (pooled OR 1.12; 95%CI 1.05-1.21; I2 36%; p = 0.002; 18 RCTs). In the NMA, atorvastatin 80 mg was associated with a highest risk of diabetes, with OR of 1.34 (95%CI 1.14-1.57) followed by rosuvastatin (OR: 1.17; 95%CI: 1.02-1.35). The ORs (95%CIs) for simvastatin 80 mg, simvastatin, atorvastatin, pravastatin, lovastatin and pitavastatin were 1.21 (0.99-1.49), 1.13 (0.99-1.29), 1.13 (0.94 1.34), 1.04 (0.93-1.16), 0.98 (0.69-1.38) and 0.74 (0.31-1.77), respectively. High-dose atorvastatin increased the odds of developing diabetes even when compared with pravastatin, simvastatin and low-dose atorvastatin in the NMA. CONCLUSIONS: Based on the results, statins, as a class, increased the risk of diabetes significantly in the pairwise meta-analysis. Overall, there appears to be a small increased risk of incident diabetes, particularly with more intensive statin therapy, although more data would be valuable to increase the robustness of this interpretation, given that the lower confidence intervals of our study analyses are close to, or just crossing one. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27277935 TI - [Evaluation of the blood progesterone concentration in the bitch measured by chemiluminescence immunoassay at the day of ovulation]. AB - OBJECTIVE: Modifications of human test systems used in veterinary laboratory practice could lead to reference-range adaptions for their veterinary use. In 2012 the manufacturer of a widely used chemiluminescence immunoassay modified the test for progesterone measurement leading to a reference range adaption for the breeding-time detection in the bitch. MATERIAL AND METHODS: The aim of the present study was to evaluate the mean progesterone concentration by using the modified chemiluminescence immunoassay at the time of ovulation in the bitch and to compare this with previously used reference ranges. Moreover, internal and external quality controls were performed and progesterone concentrations measured in different laboratories with different methods were compared at a national and international level. RESULTS: In the present study, it could be demonstrated that the concentration of progesterone of 0-6 ng/ml measured by the modified test was clearly lower than that measured by the previously delivered test. National and international quality control assurance showed a good agreement of progesterone measurements between different laboratories and with the modified test. In seven bitches, the mean progesterone concentration on the day of ultrasonographically detected ovulation was 3.4 +/- 0.9 ng/ml (2.0-4.5 ng/ml). CONCLUSION: This analysis indicates the need to change the widely accepted reference value for ovulation from 5-8 ng/ml to ~ 3.5 ng/ml for the currently used method. Particularly in veterinary endocrinology, the routine evaluation of reference values should be standard for good laboratory practice. However, the respective reference range is laboratory specific. CLINICAL RELEVANCE: Reference ranges of the progesterone concentration indicating the day of ovulation should be provided by the respective laboratory. PMID- 27277936 TI - [Representatives of orthopaedic and trauma surgery residents in Germany]. AB - In most German hospitals there are resident representatives to stand in for the rights and interests of residents. The precise number of representatives in orthopaedic and trauma surgery is unknown, as well as the field of duty and the rights of this position.The Junges Forum O&U presents survey data, which were collected from members of the German Society for Trauma Surgery (DGU), the German Society for Orthopaedics and Orthpaedic Surgery (DGOOC) and the German Society for Orthopaedics and Trauma (DGOU). All had an age below 40 years. The Survey was carried out in a period between 27th of January 2015 and 26th of March 2015.These data allowed the Junges Forum O&U to analyse the duties and numbers of representatives for residents in orthopaedic and trauma surgery in Germany. Questionnaires from 316 representatives were fully analysed. Of these, 92 % work at university hospitals. The conditions of election and the duties are not defined. The activity as representative was mainly fulfilled in spare time. The major aspect was conflict resolution between colleagues.The Junge Forum O&U presents the recommendation for election, field of duty and meetings on a regular basis with the other residents or even the first-line management. PMID- 27277937 TI - [Pre-requisites, observations and benefits of the DGU trauma registry in Austria]. AB - The trauma registry of the DGU was founded in 1992 with the objective of collecting data on severely injured patients. The purpose of this registry, in which Austrian trauma units have taken part since 1998, is to answer questions related to the field of trauma management. Using the example of the Linz Trauma Center (UKH Linz), which has actively participated since 2012, the authors would like to share their experiences of collecting data in order to motivate other departments to participate in the trauma registry. We would like to make suggestions regarding implementation methods for high-quality data acquisition.However, the availability of essential human resources must be guaranteed, since the recording of data from severely injured patients sometimes takes 60-90 min. Additionally, an automatic data acquisition method is currently unavailable for technical reasons. PMID- 27277938 TI - Echocardiographic diagnosis of double-chambered left ventricle. AB - Double-chambered left ventricle (DCLV) is a rare congenital abnormality in which the left ventricle is divided into two separate chambers by a septum or anomalous muscular structure. The chambers are observed mostly parallel to each other without stenosis, and less frequently in a superior-inferior arrangement. An asymptomatic girl is presented here who was diagnosed with DCLV on echocardiographic examination that was performed for the evaluation of cardiac murmur detected by a pediatrician. She has been followed up without treatment. PMID- 27277939 TI - Intensity of Left Atrial Spontaneous Echo Contrast as a Correlate for Stroke Risk Stratification in Patients with Nonvalvular Atrial Fibrillation. AB - The intensity of left atrial spontaneous echo contrast (LASEC) by transesophageal echocardiography (TEE) has been proposed as an important variable in the stratification of thromboembolic risk, particularly in patients with nonvalvular atrial fibrillation (NVAF). We hypothesized that the quantification of LASEC by ultrasound will improve its utility in predicting subsequent stroke events in patients with NVAF. Patients (n = 206) with definite NVAF receiving TEE were included for this prospective cohort study. Baseline clinical risk factors of stroke, CHADS2 score and CHA2DS2-Vasc, left atrial thrombus (LAT), the five grades of LASEC and video intensity (VI) value of LASEC were measured. During 2 years follow-up, 20 patients (9.7%) developed stroke. VI value of LASEC in the patients with stroke was higher compared to patients without stroke (25.30 +/- 3.61 vs. 8.65 +/- 0.81, p < 0.001). On logistic regression analysis, LAT, qualitative LASEC, graded LASEC, VI value of LASEC and CHADS2 and CHA2DS2-Vasc score were independent predictors of stroke. Among them, the highest area under the curve of receiver operating characteristic (ROC) in predicting stroke was VI value of LASEC (p < 0.05). These results show that quantification of LASEC by VI value is the most favorable predictor of stroke in patients with NVAF, and calls for improving the utility of LASEC in predicting subsequent stroke events. PMID- 27277940 TI - Should we embed randomized controlled trials within action research: arguing from a case study of telemonitoring. AB - BACKGROUND: Action research (AR) and randomized controlled trials (RCTs) are usually considered to be theoretically and practically incompatible. However, we argue that their respective strengths and weaknesses can be complementary. We illustrate our argument from a recent study assessing the effect of telemonitoring on health-related quality of life, self-care, hospital use, costs and the experiences of patients, informal carers and health care professionals in two urban hospital services and one remote rural primary care service in New Zealand. METHODS: Data came from authors' observations and field notes of discussions with three groups: the healthcare providers and healthcare consumers who participated in the research, and a group of 17 researchers and collaborators. The consumers had heart failure (Site A, urban), airways disease (Site B, urban), and diabetes (Site C, rural). The research ran from 2008 (project inception) until 2012 (project close-off). Researchers came from a wide range of disciplines. Both RCT and AR methods were recognised from early in the process but often worked in parallel rather than together. In retrospect, we have mapped our observed research processes to the AR cycle characteristics (creation of communicative space, democracy and participation, iterative learning and improvement, emergence, and accommodation of different ways of knowing). RESULTS: We describe the context, conduct and outcomes of the telemonitoring trial, framing the overall process in the language of AR. Although not fully articulated at the time, AR processes made the RCT sensitive to important context, e.g. clinical processes. They resulted in substantive changes to the design and conduct of the RCT, and to interpretation and uptake of findings, e.g. a simpler technology procurement process emerged. Creating a communicative space enabled co design between the researcher group and collaborators from the provider participant group, and a stronger RCT design. CONCLUSIONS: It appears possible to enhance the utility of RCTs by explicitly embedding them in an AR framework to shape stronger RCT design. The AR process and characteristics may enable researchers to evaluate telehealth while enhancing rather than compromising the quality of an RCT, where research results are returned to practice as part of the research process. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, reference ACTRN12610000269033 . PMID- 27277942 TI - Behind the Smile. PMID- 27277941 TI - The effect of an affordable daycare program on health and economic well-being in Rajasthan, India: protocol for a cluster-randomized impact evaluation study. AB - BACKGROUND: The provision of affordable and reliable daycare services is a potentially important policy lever for empowering Indian women. Access to daycare might reduce barriers to labor force entry and generate economic opportunities for women, improve education for girls caring for younger siblings, and promote nutrition and learning among children. However, empirical evidence concerning the effects of daycare programs in low-and-middle-income countries is scarce. This cluster-randomized trial will estimate the effect of a community-based daycare program on health and economic well-being over the life-course among women and children living in rural Rajasthan, India. METHODS: This three-year study takes place in rural communities from five blocks in the Udaipur District of rural Rajasthan. The intervention is the introduction of a full-time, affordable, community-based daycare program. At baseline, 3177 mothers with age eligible children living in 160 village hamlets were surveyed. After the baseline, these hamlets were randomized to the intervention or control groups and respondents will be interviewed on two more occasions. Primary social and economic outcomes include women's economic status and economic opportunity, women's empowerment, and children's educational attainment. Primary health outcomes include women's mental health, as well as children's nutritional status. DISCUSSION: This interdisciplinary research initiative will provide rigorous evidence concerning the effects of daycare in lower-income settings. In doing so it will address an important research gap and has the potential to inform policies for improving the daycare system in India in ways that promote health and economic well-being. TRIAL REGISTRATION: (1) The ISRCTN clinical trial registry (ISRCTN45369145), http://www.isrctn.com/ISRCTN45369145 , registered on May 16, 2016 and (2) The American Economic Association's registry for randomized controlled trials (AEARCTR-0000774), http://www.socialscienceregistry.org/trials/774 , registered on July 15, 2015. PMID- 27277943 TI - Isotope-filtered nD NMR spectroscopy of complex mixtures to unravel the molecular structures of phenolic compounds in tagged soil organic matter. AB - Unravelling structures of molecules contained in complex, chromatographically inseparable mixtures is a challenging task. Due to the number of overlapping resonances in NMR spectra of these mixtures, unambiguous chemical shift correlations attributable to individual molecules cannot be achieved and thus their structure determination is elusive by this technique. Placing a tag carrying an NMR active nucleus onto a subset of molecules enables (i) to eliminate signals from the non-tagged molecules, and (ii) to obtain a set of correlated chemical shifts and coupling constants belonging to a single molecular type. This approach provides an opportunity for structure determination without the need for compound separation. Focusing on the most abundant functional groups of natural organic matter molecules, the carboxyl and hydroxyl groups were converted into esters and ethers, respectively by introducing (13)CH3O groups. A set of (13)C-filtered nD NMR experiments was designed yielding structures/structural motives of tagged molecules. The relative sensitivity of these experiments was compared and a step-by-step guide how to use these experiments to analyse the structures of methylated phenolics is provided. The methods are illustrated using an operational fraction of soil organic matter, fulvic acid isolated from a Scottish peat bog. Analysis of 33 structures identified in this sample revealed a correlation between the position of the methoxy cross-peaks in the (1)H, (13)C HSQC spectra and the compound type. This information enables profiling of phenolic compounds in natural organic matter without the need to acquire a full set of experiments described here or access to high field cryoprobe NMR spectrometers. PMID- 27277944 TI - 2016 European guideline on the management of non-gonococcal urethritis published. PMID- 27277945 TI - The Home Observation of Periconceptional Exposures (HOPE) study, a prospective cohort: aims, design, recruitment and compliance. AB - BACKGROUND: To examine transient environmental exposures and their relationship with human fecundity, exposure assessment should occur optimally at the time of conception in both members of the couple. We performed an observational, prospective cohort study with biomonitoring in both members of a heterosexual couple trying to conceive. Couples collected urine, saliva, and semen specimens for up to two menstrual cycles on days corresponding to the time windows of fertilization, implantation, and early pregnancy, identified based on the woman's observations of her cervical fluid. RESULTS: Three hundred nine eligible couples were screened between 2011 and 2015, of which 183 enrolled. Eleven couples (6.0 %) withdrew or were lost to follow up. The most successful and cost effective recruiting strategies were word of mouth (40 % of participating couples), posters and flyers (37 %), and targeted Facebook advertising (13 %) with an overall investment of $37.35 spent on recruitment per couple. Both men and women collected >=97.2 % of requested saliva samples, and men collected >=89.9 % of requested semen samples. Within the periovulatory days (+/-3 days), there was at least one urine specimen collected by women in 97.1 % of cycles, and at least one by men in 91.7 % of cycles. Daily compliance with periovulatory urine specimens ranged from 66.5 to 92.4 % for women and from 55.7 to 75.0 % for men. Compliance was >=88 % for questionnaire completion at specified time points. CONCLUSIONS: Couples planning to conceive can be recruited successfully for periconceptional monitoring, and will comply with intensive study protocols involving home collection of biospecimens and questionnaire data. PMID- 27277947 TI - Fibula regeneration following non-vascularized graft harvest in children. AB - BACKGROUND: A peculiarity of non-vascularized fibular harvest is that the donor site regenerates new bone provided periosteum is preserved. We prospectively investigated the regenerated fibula quantitatively and studied clinical implications of non-regeneration. MATERIAL AND METHODS: The fibula was harvested using a periosteum preserving technique. Only fibulae from healthy legs were harvested. X-rays were done pre- and post-operatively at three and six months. Clinical assessment of donor limb included pain, gait, motor and sensory examination. Fibular regeneration was quantified using defined length and width criteria. RESULTS: There were 16 children with 21 harvested fibula. About 65 % of total fibular length was available for use as graft. There was regeneration of fibula similar to the pre-operative dimensions as early as six months in 71 % of cases. There were no clinical morbid findings as assessed at six months follow up despite non-continuity being observed in 29 % of cases. The predominant site for non-continuity was middle third-distal third junction. CONCLUSIONS: Periosteal preserving non-vascularized fibula grafting was a low morbidity procedure. In two third of the cases, there was regeneration of fibula comparable to pre-operative dimensions as early as six months. The non-continuous regeneration had no clinical implications. PMID- 27277948 TI - Accuracy of measuring acetabular cup position after total hip arthroplasty: comparison between a radiographic planning software and three-dimensional computed tomography. AB - PURPOSE: Various methods are available for measuring acetabular cup position after total hip arthroplasty (THA) on standard anterior-posterior (AP) radiographs. We compared the accuracy of a commercial radiographic planning software program with that of three-dimensional computed tomography (3D-CT) scans. METHODS: We obtained plain AP radiographs and 3D-CTs from 65 patients after THA. In addition to calculating cup anteversion and inclination with 3D-CT, we determined the cup position using the radiographic planning software program mediCAD(r) 2.5 (Hectec, Niederviehbach, Germany). Furthermore, we compared the measurements using the inter-teardrop and bi-ischial lines as pelvic landmarks. RESULTS: The mean difference in anteversion between 3D-CT and mediCAD(r) software was 0.1 degrees using the inter-teardrop line (standard deviation [SD], 8.8 degrees ; range, -21 degrees to 23 degrees ; p = 0.97) and 0.4 degrees using the bi-ischial line (SD, 8.8 degrees ; range, -23 degrees to 21 degrees ; p = 0.72). Inclination showed a mean difference of 0.6 degrees using the inter teardrop line (SD, 4.4 degrees ; range, -9 degrees to 21 degrees ; p = 0.24) and 0.5 degrees using bi-ischial line (SD, 4.6 degrees ; range, -9 degrees to 22 degrees ; p = 0.35). The means for absolute differences were 7.2 degrees for anteversion and 3.1 degrees for inclination. With regard to using the bi-ischial or inter-teardrop line, no significant difference was found between the two pelvic landmarks. The intra-class correlation coefficient (ICC) was analysed for anteversion and inclination using either the inter-teardrop line or the bi ischial line as radiographic baseline. CONCLUSIONS: A radiographic planning software program (mediCAD(r)) is a helpful tool for measuring cup inclination on AP radiographs. With respect to anteversion, measurements are rather susceptible to mistakes with mean inaccuracies of over 7 degrees . Thus, 3D-CT remains the "gold standard" if a lower tolerance limit (+/-3 degrees ) is required for more complex biomechanical evaluations. As a pelvic landmark, the interteardrop line is preferential to the bi-ischial line because of its lower impact on the position of the pelvis. PMID- 27277946 TI - Prevention of depression through nutritional strategies in high-risk persons: rationale and design of the MooDFOOD prevention trial. AB - BACKGROUND: Obesity and depression are two prevalent conditions that are costly to individuals and society. The bidirectional association of obesity with depression, in which unhealthy dietary patterns may play an important role, has been well established. Few experimental studies have been conducted to investigate whether supplementing specific nutrients or improving diet and food related behaviors can prevent depression in overweight persons. METHOD/DESIGN: The MooDFOOD prevention trial examines the feasibility and effectiveness of two different nutritional strategies [multi-nutrient supplementation and food-related behavioral change therapy (FBC)] to prevent depression in individuals who are overweight and have elevated depressive symptoms but who are not currently or in the last 6 months meeting criteria for an episode of major depressive disorder (MDD). The randomized controlled prevention trial has a two-by-two factorial design: participants are randomized to daily multi-nutrient supplement (omega-3 fatty acids, calcium, selenium, B-11 vitamin and D-3 vitamin) versus placebo, and/or FBC therapy sessions versus usual care. Interventions last 12 months. In total 1000 participants aged 18-75 years with body mass index between 25-40 kg/m(2) and with a Patient Health Questionnaire-9 score >= 5 will be recruited at four study sites in four European countries. Baseline and follow-up assessments take place at 0, 3, 6, and 12 months. Primary endpoint is the onset of an episode of MDD, assessed according to DSM-IV based criteria using the MINI 5.0 interview. Depressive symptoms, anxiety, food and eating behavior, physical activity and health related quality of life are secondary outcomes. During the intervention, compliance, adverse events and potentially mediating variables are carefully monitored. DISCUSSION: The trial aims to provide a better understanding of the causal role of specific nutrients, overall diet, and food-related behavior change with respect to the incidence of MDD episodes. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective nutritional public health strategies for the prevention of clinical depression. TRIAL REGISTRATION: ClinicalTrials.gov. Number of identification: NCT02529423 . August 2015. PMID- 27277949 TI - N-ethylmaleimide-sensitive factor siRNA inhibits the release of Weibel-Palade bodies in endothelial cells. AB - The aim of the present study was to examine the effect of small interfering RNA (siRNA) methods on the expression of N-ethylmaleimide sensitive factor (NSF) and Weibel-Palade body (WPB) release in endothelial cells. A small hairpin RNA (shRNA), mediated with an adenovirus vector, was designed to target the N terminal functional area of NSF. Subsequently, viruses were transfected into human aortic endothelial cells. The mRNA and protein expression levels of NSF were detected using reverse transcription-quantitative polymerase chain reaction and Western blot analyses, respectively, and the release of WPBs in the endothelial cells was examined using immunofluorescence. The mRNA expression of NSF in the endothelial cells, which were transfected with the adenoviruses carrying the NSF-shRNA was significantly decreased, compared with the negative control group (P=0.035) and blank control group (P=0.02). In addition, the mRNA expression of NSF was gradually decreased as duration increased; there were marked differences between the 24, 48 and 72 h groups (P<0.05). The protein expression of NSF was significantly decreased in the experimental group, compared with the negative control group (P=0.004) and blank control group (P=0.031), however, no difference was observed between the negative control and blank control groups (P=0.249). The immunofluorescence staining showed that the release of WPBs in the endothelial cells induced with thrombin was inhibited markedly following transfection with the virus carrying the NSF-shRNA. Therefore NSF-siRNA inhibited the mRNA and protein expression levels of NSF, and inhibited the release of WPBs in endothelial cells induced with thrombin. These results suggested that NSF-siRNA may be valuable for preventing and treating atherosclerosis and acute coronary syndrome. PMID- 27277950 TI - Attention bias to threat indicates anxiety differences in sheep. AB - Humans and animals show increased attention towards threatening stimuli when they are in increased states of anxiety. The few animal studies that have examined this phenomenon, known as attention bias, have applied environmental manipulations to induce anxiety but the effects of drug-induced anxiety levels on attention bias have not been demonstrated. Here, we present an attention bias test to identify high and low anxiety states in sheep using pharmacological manipulation. Increased anxiety was induced using 1-methyl-chlorophenylpiperazine (m-CPP) and decreased anxiety with diazepam, and then we examined the behaviour of sheep in response to the presence of a dog as a threat. Increased attention towards the threat and increased vigilance were shown in sheep that received the m-CPP and reduced in sheep receiving the diazepam. The modulated attention towards a threat displayed by the m-CPP and diazepam animals suggests that attention bias can assess different levels of anxiety in sheep. Measuring attention bias has the potential to improve animal welfare assessment protocols. PMID- 27277951 TI - The potential for sexual transmission to compromise control of Ebola virus outbreaks. AB - Recent evidence suggests that sexual contact may give rise to transmission of Ebola virus long after infection has been cleared from blood. We develop a simple mathematical model that incorporates contact transmission and sexual transmission parametrized from data relating to the 2013-2015 West African Ebola epidemic. The model explores scenarios where contact transmission is reduced following infection events, capturing behaviour change, and quantifies how these actions reducing transmission may be compromised by sexual transmission in terms of increasing likelihood, size and duration of outbreaks. We characterize the extent to which sexual transmission operates in terms of the probability of initial infection resolving to sexual infectiousness and the sexual transmission rate, and relate these parameters to the overall case burden. We find that sexual transmission can have large effects on epidemic dynamics (increasing attack ratios from 25% in scenarios without sexual transmission but with contact transmission-reducing behaviour, up to 80% in equivalent scenarios with sexual transmission). PMID- 27277952 TI - On the prior distribution of extinction time. AB - Bayesian inference about the extinction of a species based on a record of its sightings requires the specification of a prior distribution for extinction time. Here, I critically review some specifications in the context of a specific model of the sighting record. The practical implication of the choice of prior distribution is illustrated through an application to the sighting record of the Caribbean monk seal. PMID- 27277953 TI - Intra-ejaculate sperm selection in female zebra finches. AB - Among internal fertilizers, typically fewer than 1% sperm survive the journey through the oviduct. Several studies suggest that the sperm reaching the ovum-the 'fertilizing set'-comprise a non-random sub-population, but the characteristics of this group remain unclear. We tested whether oviductal selection in birds results in a morphologically distinct subset of sperm, by exploiting the fact that the fertilizing set are trapped by the perivitelline layer of the ovum. We show that these sperm have remarkably low morphological variation, as well as smaller head size and greater tail length, compared with those inseminated. Our study shows that the morphological composition of sperm-rather than length alone influences success in reaching the ovum. PMID- 27277954 TI - Distinct effects of pollinator dependence and self-incompatibility on pollen limitation in South African biodiversity hotspots. AB - Global synthesis indicates that limitation of plant fecundity by pollen receipt (pollen limitation) is positively related to regional plant diversity and is higher for self-incompatible than self-compatible species. While self incompatible species are always dependent on pollinating agents, self-compatible species may be pollinator-dependent or autofertile. This should cause variation in pollen limitation among self-compatible species, with lower pollen limitation in autofertile species because they do not depend on pollinators. We hypothesized that the intensity of pollen limitation in self-incompatible compared with pollinator-dependent self-compatible species should depend on whether pollen limitation is determined more by quantity than quality of pollen received. We compared pollen limitation between these three groups using a dataset of 70 biotically pollinated species from biodiverse regions of South Africa. Comparison with a global dataset indicated that pollen limitation in the South African biodiversity hotspots was generally comparable to other regions, despite expectations of higher pollen limitation based on the global plant diversity pollen limitation relationship. Pollen limitation was lowest for autofertile species, as expected. It was also higher for pollinator-dependent self-compatible species than self-incompatible species, consistent with increased pollen-quality limitation in the former group due to negative consequences of pollinator mediated self-pollination. However, there was a higher frequency of plants with zygomorphic flowers, which were also more pollen-limited, among pollinator dependent self-compatible species. Thus, we could not attribute this difference in pollen limitation exclusively to a difference in pollen quality. Nevertheless, our results indicate that comparative studies should control for both pollinator dependence and self-incompatiblity when evaluating effects of other factors on pollen limitation. PMID- 27277955 TI - An Infant with a Prolonged Sympathomimetic Toxidrome after Lisdexamfetamine Dimesylate Ingestion. AB - INTRODUCTION: Stimulant medications are approved to treat attention deficit hyperactivity disorder (ADHD) in children over the age of 6 years. Fatal ingestion of stimulants by children has been reported, although most ingestions do not result in severe toxicity. Lisdexamfetamine dimesylate, a once daily long acting stimulant, is a prodrug requiring conversion to its active form, dextroamphetamine, in the bloodstream. Based on its unique pharmacokinetics, peak levels of d-amphetamine are delayed. We describe a case of accidental ingestion of lisdexamfetamine dimesylate in an infant. CASE REPORT: A previously healthy 10 month-old infant was admitted to the hospital with a 5-h history of tachycardia, hypertension, dyskinesia, and altered mental status of unknown etiology. Confirmatory urine testing, from a specimen collected approximately 16 h after the onset of symptoms, revealed an urine amphetamine concentration of 22,312 ng/mL (positive cutoff 200 ng/mL). The serum amphetamine concentration, from a specimen collected approximately 37 h after the onset of symptoms, was 68 ng/mL (positive cutoff 20 ng/mL). Urine and serum were both negative for methamphetamine, methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA, Ecstasy), and methylenedioxyethamphetamine (MDEA). During the hospitalization, it was discovered that the infant had access to lisdexamfetamine dimesylate prior to the onset of symptoms. CONCLUSION: Amphetamine ingestions in young children are uncommon but do occur. Clinicians should be aware of signs and symptoms of amphetamine toxicity and consider ingestion when a pediatric patient presents with symptoms of a sympathetic toxidrome even when ingestion is denied. PMID- 27277956 TI - Evolutionary consequences of polyploidy in prokaryotes and the origin of mitosis and meiosis. AB - BACKGROUND: The origin of eukaryote-specific traits such as mitosis and sexual reproduction remains disputable. There is growing evidence that both mitosis and eukaryotic sex (i.e., the alternation of syngamy and meiosis) may have already existed in the basal eukaryotes. The mating system of the halophilic archaeon Haloferax volcanii probably represents an intermediate stage between typical prokaryotic and eukaryotic sex. H. volcanii is highly polyploid, as well as many other Archaea. Here, we use computer simulation to explore genetic and evolutionary outcomes of polyploidy in amitotic prokaryotes and its possible role in the origin of mitosis, meiosis and eukaryotic sex. RESULTS: Modeling suggests that polyploidy can confer strong short-term evolutionary advantage to amitotic prokaryotes. However, it also promotes the accumulation of recessive deleterious mutations and the risk of extinction in the long term, especially in highly mutagenic environment. There are several possible strategies that amitotic polyploids can use in order to reduce the genetic costs of polyploidy while retaining its benefits. Interestingly, most of these strategies resemble different components or aspects of eukaryotic sex. They include asexual ploidy cycles, equalization of genome copies by gene conversion, high-frequency lateral gene transfer between relatives, chromosome exchange coupled with homologous recombination, and the evolution of more accurate chromosome distribution during cell division (mitosis). Acquisition of mitosis by an amitotic polyploid results in chromosome diversification and specialization. Ultimately, it transforms a polyploid cell into a functionally monoploid one with multiple unique, highly redundant chromosomes. Specialization of chromosomes makes the previously evolved modes of promiscuous chromosome shuffling deleterious. This can result in selective pressure to develop accurate mechanisms of homolog pairing, and, ultimately, meiosis. CONCLUSION: Emergence of mitosis and the first evolutionary steps towards eukaryotic sex could have taken place in the ancestral polyploid, amitotic proto-eukaryotes, as they were struggling to survive in the highly mutagenic environment of the Early Proterozoic shallow water microbial communities, through the succession of the following stages: (1) acquisition of high-frequency between-individual genetic exchange coupled with homologous recombination; (2) acquisition of mitosis, followed by rapid chromosome diversification and specialization; (3) evolution of homolog synapsis and meiosis. Additional evidence compatible with this scenario includes mass acquisition of new families of paralogous genes by the basal eukaryotes, and recently discovered correlation between polyploidy and the presence of histones in Archaea. REVIEWER: This article was reviewed by Eugene Koonin, Uri Gophna and Armen Mulkidjanian. For the full reviews, please go to the Reviewers' comments section. PMID- 27277958 TI - Left main occlusion - a classic electrocardiogram. AB - Left main occlusion is associated with a dire prognosis, as the left main supplies blood to >75 % of the left ventricle. This is a case showing a classic electrocardiogram (ECG) together with the echocardiogram videos and images from coronary angiography. PMID- 27277957 TI - Genetically encoded optical activation of DNA recombination in human cells. AB - We developed two tightly regulated, light-activated Cre recombinase enzymes through site-specific incorporation of two genetically-encoded photocaged amino acids in human cells. Excellent optical off to on switching of DNA recombination was achieved. Furthermore, we demonstrated precise spatial control of Cre recombinase through patterned illumination. PMID- 27277960 TI - Motivating basic research in the university. PMID- 27277959 TI - Maternal morbidity measurement tool pilot: study protocol. AB - BACKGROUND: While it is estimated that for every maternal death, 20-30 women suffer morbidity, these estimates are not based on standardized methods and measures. Lack of an agreed-upon definition, identification criteria, standardized assessment tools, and indicators has limited valid, routine, and comparable measurements of maternal morbidity. The World Health Organization (WHO) convened the Maternal Morbidity Working Group (MMWG) to develop standardized methods to improve estimates of maternal morbidity. To date, the MMWG has developed a definition and provided input into the development of a set of measurement tools. This protocol outlines the pilot test for measuring maternal morbidity in antenatal and postnatal clinical populations using these new tools. METHODS: In each setting, the tools will be piloted on approximately 250 women receiving antenatal care (ANC) (at least 28 weeks pregnant) and 250 women receiving postpartum care (PPC) (at least 6 weeks postpartum). The tools will be administered by trained health care workers. Each tool has three modules as follows: 1. personal history - socio-economic information, and risk-factors (such as violence and substance abuse) 2. patient symptoms - WHO Disability Assessment Schedule (WHODAS) 12-item, and mental health questionnaires, General Anxiety Disorder, 7-item (GAD-7) and Personal Health Questionnaire, 9-item (PHQ 9) 3. physical examination - signs, laboratory tests and results. DISCUSSION: This pilot (planned for Jamaica, Kenya and Malawi) will allow for comparing the types of morbidities women experience between and across settings, and determine the feasibility, acceptability and utility of using a modified, streamlined tool for routine measurement and summary estimates of morbidity to inform resource allocation and service provision. As part of the post-2015 Sustainable Development Goals (SDGs) estimating and measuring maternal morbidity will be essential to ensure appropriate resources are allocated to address its impact and improve well-being. PMID- 27277961 TI - Elastography: Imaging the elastic properties of soft tissues with ultrasound. AB - Elastography is a method that can ultimately generate several new kinds of images, called elastograms. As such, all the properties of elastograms are different from the familiar properties of sonograms. While sonograms convey information related to the local acoustic backscatter energy from tissue components, elastograms relate to its local strains, Young's moduli or Poisson's ratios. In general, these elasticity parameters are not directly correlated with sonographic parameters, i.e. elastography conveys new information about internal tissue structure and behavior under load that is not otherwise obtainable. In this paper we summarize our work in the field of elastography over the past decade. We present some relevant background material from the field of biomechanics. We then discuss the basic principles and limitations that are involved in the production of elastograms of biological tissues. Results from biological tissues in vitro and in vivo are shown to demonstrate this point. We conclude with some observations regarding the potential of elastography for medical diagnosis. PMID- 27277962 TI - Sound waves and antineoplastic drugs: The possibility of an enhanced combined anticancer therapy. AB - Kremkau wrote a historical review of the use of ultrasound in cancer therapy in 1979((1)) In 1990, Kondo and Kano published a Japanese review of the implications of the thermal and nonthermal effects of ultrasound in the treatment of cancer(2)). Again in 2000, Kondo et al reviewed the therapeutic applications of ultrasound and shock wave, emphasizing their thermal and cavitational effects(3)). Here we focus on the effects of ultrasound or shock waves in combination with anticancer agents, emphasizing their mechanisms of action and interaction. Most of the studies cited here reported promising results. Although the extent of the augmented combined effects in vivo is limited, synergism is the rule in vitro. In addition to the thermal effect of ultrasound, cavitational effects undoubtedly played a major role in both ultrasound and, more prominently, in shock wave therapy. Although the mechanism of the nonthermal noncavitational effects on biological processes is obscure, several factors, including temperature and the occurrence of cavitation and inertial cavitation, probably coexist and blend with these other effects. Magnification of anticancer activity results mainly from increased localization of drugs or other agents in vivo and increased intracellular permeabilisation both in vivo and in vitro. On the other hand, sublethal damage caused by ultrasound or shock waves may render cells more susceptible, to the effects of the agents, and both may act together, further amplifying these effects. We thus conclude that proper combination of an appropriate agent and ultrasound or shock wave should help improve cancer therapy by minimizing the side effects of drugs by lowering the effective dose and reducing the systemic concentration while increasing the efficiency of the therapy as a whole. Future studies should reveal specific conditions in this combined therapy that will lead to optimal outcome. PMID- 27277964 TI - Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging: Preliminary results in hepatic tumors. AB - PURPOSE: To investigate the usefulness of contrast advanced dynamic flow imaging and contrast pulse subtraction imaging in the intranodular hemodynamics of hepatic tumors. MATERIALS AND METHODS: Ten patients underwent contrast advanced dynamic flow imaging and contrast pulse subtraction imaging using Levovist((r)), a microbubble contrast agent. Fourteen hepatic tumor nodules were studied: 9 were hepatocellular carcinoma, 1 metastasis, 1 hemangioma, 1 adenomatous hyperplasia, and 2 metastatic lymph nodes of hepatocellular carcinoma. Real-time scanning of contrast advanced dynamic flow imaging and intermittent interval-delay scanning of contrast pulse subtraction imaging were carried out in the early arterial phase, the late vascular phase, and the postvascular phase. The results obtained from contrast advanced dynamic flow imaging and contrast pulse subtraction imaging were compared with those obtained by precontrast power Doppler imaging and three-phase dynamic CT, respectively. RESULTS: The rate of detection of intranodular vascularity by contrast advanced dynamic flow imaging (93%) or contrast pulse subtraction imaging (93%) was significantly higher than that of precontrast power Doppler imaging (29%) and was as high as that of dynamic CT. Characteristic intranodular hemodynamics were detected in hepatocellular carcinoma, metastasis, hemangioma, and adenomatous hyperplasia with typical appearance of an intranodular blood vessel image in the early arterial phase, a parenchymal stain image in the late vascular phase, and a perfusion defect image in the post-vascular phase. CONCLUSION: Contrast advanced dynamic flow imaging and contrast pulse subtraction imaging clearly show the intranodular hemodynamics in hepatic tumors. PMID- 27277963 TI - Doppler ultrasound measurement of cerebral blood flow in healthy pregnant women. AB - PURPOSE: To compare global cerebral blood supply in healthy pregnant women and nonpregnant women. MATERIALS AND METHODS: Flow volumes in the common, internal, and external carotid, arteries and the vertebral arteries were determined using color Doppler ultrasonography in 17 nonpregnant women, 55 healthy pregnant women at 10 to 40 weeks gestation, and 24 puerperal women within 1 week after spontaneous delivery. Global cerebral blood flow was defined as the sum of flow volumes in the bilateral internal carotid and vertebral arteries. RESULTS: In the nonpregnant group, mean flow volumes of the common, internal, and external carotid arteries and the vertebral arteries, and mean global cerebral blood flow volume were (mean+/-SD) 863+/-108 ml/min, 554 +/-94 ml/min, 386+/-65 ml/min, 115+/-24 ml/min, and 669+/-104 ml/min, respectively. During the second trimester, flow volumes of the common and external carotid arteries increased significantly in the healthy pregnant women, to about 130 percent and 140 percent of the nonpregnant level, respectively. Global cerebral blood flow volume remained unchanged during pregnancy. CONCLUSION: During pregnancy, increase in flow volumes in the common carotid arteries were accompanied by elevated flow volumes of the external carotid arteries but not the internal carotid arteries. This distribution would tend to regulate the volume of global cerebral blood flow throughout the period of pregnancy. PMID- 27277965 TI - The efferent blood flow of early hepatocellular carcinoma and borderline lesions: Demonstration by color Doppler imaging. AB - We performed waveform analysis of the efferent signal detected within early hepatocellular carcinomas and borderline lesions, in which portal flow was demonstrated. Continuity of this flow with the surrounding vessels was also analyzed. Nine nodules in 7 patients with early hepatocellular carcinomas and borderline lesions were included in this study. Tumor diameter ranged from 1.2 to 3.5 cm; average, 2.1 cm. Waveform of the efferent flow signal from within these nodules was continuous in 5 nodules and biphasic venous in 4 nodules. Outside the nodules, the waveform of the efferent flow signal was that of a biphasic venous wave. All efferent signals were confirmed to continue in the hepatic vein. These findings thus suggest that the draining vessel in early hepatocellular carcinomas and their borderline lesions is the hepatic vein. PMID- 27277966 TI - Studies on tissue characterization by texture analysis with co-occurrence matrix method using ultrasonography and CT imaging. AB - We used texture analysis with the co-occurrence matrix method to analyze ultrasonograms from normal and diseased livers, and X-ray CT images obtained from normal cases and cases of idiopathic interstitial pneumonia. Ten cases of normal, fatty, and cirrhotic livers; 10 cases of normal lungs; and 10 cases of idiopathic interstitial pneumonia, all confirmed by clinical findings, laboratory data, surgery, or biopsy, were the subjects of this study. We compared the results of texture analysis in normal and diseased livers under the same conditions of gain, focus, magnification rate, probe frequency, and depth of the region of interest. Here we discuss the relationship between Fisher ratio of texture analysis and pathological character. Although the normal and diseased liver groups did not differ significantly, the different pathological grades of fibrosis and the different size of nodules in the cirrhotic and normal liver groups did have different Fisher ratios. We compared the results of texture analysis with images obtained from normal cases and cases of idiopathic interstitial pneumonia. Significant differences between normal lungs and those with idiopathic interstitial pneumonia were also found. We thus think that texture analysis can be used to analyze ultrasonograms obtained from lesions of different pathological grades and to classify CT images as well. PMID- 27277968 TI - Fetal ascites immediately after rupture of ovarian cysts. AB - Ruptured fetal ovarian cysts are difficult to diagnose. We report on ultrasonograms recorded before and immediately after spontaneous rupture of fetal ovarian cysts followed by transient ascites. Ultrasound findings of transient ascites accompanied by rapid reduction in cyst size could aid in diagnosing rupture of fetal ovarian cysts. PMID- 27277967 TI - Short-term therapy with relatively low-dose cerivastatin improves endothelial function independently of its lipid-lowering effect: Evaluation of brachial artery vasodilatation using B-mode ultrasound imaging. AB - BACKGROUND AND OBJECTIVE: Administration of 0.4 to 0.8 mg of cerivastatin per day for 2 weeks has been reported to have pleiotropic effects and improve endothelial function. Whether low-dose cerivastatin would produce these rapid pleiotropic effects in the clinical setting remains uncertain, however. We investigated the effect of short-term therapy with relatively low-dose cerivastatin (0.15 mg/day) on endothelial function, thrombostatic parameters, and C-reactive protein (CRP) levels in hypercholesterolemic patients. METHODS: Thirteen patients with LDL cholesterol>160 mg/dl were treated with daily doses of 0.15 mg of cerivastatin for 2 weeks. Endothelial function, thrombostatic parameters (tissue-type plasminogen activator [t-PA], plasminogen activator inhibitor type 1 [PAI-1], and CRP were estimated at baseline and again after 2 weeks of treatment. Endothelial function was measured as flow-mediated vasodilation. Flow-mediated vasodilatation was assessed by measuring the percent change in the diameter of the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Endothelium-independent vasodilatation was also measured using sublingual nitroglycerin. RESULTS: No major complications developed after the treatment. Total cholesterol decreased significantly, from 258+/-32 to 211+/-21 mg/dl, and LDL-cholesterol also decreased from 171+/-15 to 133+/-16 mg/dl after the treatment. Flow-mediated vasodilatation increased significantly, from 4.6+/-1.3 percent to 8.7+/-3.5 percent after 2 weeks of therapy, although endothelium independent vasodilatation was not affected (9.5+/-2.4% vs 8.8+/-3.1%). No relation was found between percent change in flow-mediated vasodilatation and improvement in levels of LDL-cholesterol after therapy (r=0.07). PAI-1, t-PA, and CRP were not significantly changed by 2 weeks of therapy. CONCLUSIONS: (1) Evaluating vasodilation of the brachial artery with B-mode ultrasound imaging was useful in investigating the effect of statin on endothelial function. (2) Although no effect was detected in PAI-1, t-PA, or CRP, relatively low-dose cerivastatin therapy for 2 weeks improved endothelial function and lipid level independently and safely in hypercholesterolemic patients. PMID- 27277970 TI - RUNX2 controls human IPO8 basal transcription in Saos-2 cells. AB - Runt-related transcription factor 2 (RUNX2) is a vital regulatory factor that controls osteoblast-specific gene expression; however, RUNX2-regulated genes in human mesenchymal stem cells (hMSCs) remain to be fully elucidated. In the present study, chromatin immunoprecipitation (ChIP)-on-chip analysis of RUNX2 in hMSCs demonstrated that importin 8 (IPO8) may be a novel target gene. The 5' flanking region of the IPO8 gene, which is ~3,300 bp in length, was cloned and inserted into the pGL3-basic luciferase reporter vector. The results of dual luciferase reporter assays indicated that this segment possessed strong basal promoter activity. Furthermore, the RUNX2 binding site, which encompasses positions -496 to -501 bp, was required to achieve maximal IPO8 promoter activity in Saos-2 human osteosarcoma cells. In addition, ChIP analysis indicated that RUNX2 uniquely binds to this specific IPO8 sequence motif. Cells with a knockdown in RUNX2 expression exhibited downregulated IPO8 transcription. Finally, synchronization of IPO8 and RUNX2 expression was observed in Saos-2 cells cultured in osteoblast-induction medium. Taken together, these results indicated that RUNX2 regulates IPO8 gene transcription, and may have a contributory role in osteoblast differentiation. PMID- 27277971 TI - Symptoms and musculoskeletal diseases in hospital nurses and in a group of university employees: a cross-sectional study. AB - BACKGROUND: Most studies have shown that nurses have a higher risk of developing musculoskeletal symptoms compared with other occupational groups. AIM: A cross sectional study was performed to gain more insight into the prevalence rates of musculoskeletal disorders (MSDs) in nurses. METHODS: The presence of musculoskeletal symptoms was revealed by personal interviews in a sample of 177 hospital nurses and in a reference group of 185 university employees. Musculoskeletal diseases were based on radiological examinations in all subjects. RESULTS: Lower back pain (61% vs 42.2%) was the most frequently reported symptom, followed by neck pain (48.6% vs 38.4%) and shoulder pain (36.7% vs 25.9%), with a significantly higher prevalence in nurses. Women had about a 2-fold risk of upper limb region and neck pain compared with men. The most common abnormal findings on radiological examinations were disc herniations (n = 40). CONCLUSIONS: Nurses showed a significantly higher risk of MSDs. Prevalence rates in nurses increased significantly with age. Musculoskeletal symptoms were also common in university employees. This suggests the need for effective intervention strategies involving workers' active participation, in order to improve the process and organization of work and promote a positive psychosocial work environment. PMID- 27277974 TI - Safety of ultrasound diagnosis. PMID- 27277972 TI - The satiety factor oleoylethanolamide impacts hepatic lipid and glucose metabolism in goldfish. AB - Oleoylethanolamide (OEA) is an acylethanolamide synthesized mainly in the gastrointestinal tract with known effects in mammals on food intake and body mass through activation of peroxisome proliferator-activated receptor type alpha (PPARalpha). Since we previously demonstrated that acute treatment with OEA in goldfish resulted in decreased food intake and locomotor activity, as in mammals, we hypothesize that OEA would be involved in the control of energy metabolism in fish. Therefore, we assessed the effects of acute (for 6 h) and chronic (for 11 days) treatments with OEA (5 ug g-1 body mass) on metabolite concentrations and enzyme activities related to glucose and lipid metabolism in liver of goldfish (Carassius auratus). In the chronic treatment, OEA impairs the increase in body mass and reduces locomotor activity, without any signs of stress. The lipolytic capacity in liver decreased after both acute and chronic OEA treatments, whereas lipogenic capacity increased after acute and decreased after chronic treatment with OEA. These results are different from those observed to date in mammalian adipose tissue, but not so different from those known in liver, and might be attributed to the absence of changes in the expression of pparalpha, and/or to the increase in the expression of the clock gene bmal1a after chronic OEA treatment. As for glucose metabolism, a clear decrease in the capacity of hepatic tissue to use glucose was observed in OEA-treated fish. These results support an important role for OEA in the regulation of liver lipid and glucose metabolism, and could relate to the metabolic changes associated with circadian activity and the regulation of food intake in fish. PMID- 27277973 TI - Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy. AB - Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2 (trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38, and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5, and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy. PMID- 27277975 TI - Volume measurement of a pediatric ventricular phantom model using three dimensional echocardiography. AB - PURPOSE: Volume measurement of the ventricle is necessary to evaluate cardiac function. Accurate volume measurement of the ventricle by three-dimensional (3D) echocardiography will mark a new step in pediatric cardiovascular diagnosis and treatment. We studied volume measurement of a pediatric ventricular model using 3D echocardiography. METHODS: The ultrasonic diagnostic setup used in this study comprised a Philips Sonos 7500 ultrasound system with an electronic sector probe of a *4 matrix phased array transducer. The ventricular model was made from a latex surgical glove. The tip of the third finger of the glove was cut off and fixed to a manifold. The ventricular model was gently placed in a reservoir filled with water. Volumes of physiological saline solution ranging from 2 ml to 50 ml in 2-ml increments were injected into the ventricular model and examined. Twenty-five ultrasound images of the ventricular model were obtained using 4D Cardio View RT 1.2 software. RESULTS: There was excellent correlation and agreement between the injected volumes and the calculated volumes (Y = -0.539 + 1.005X, r = 0.997, four cut plane; Y = -0.191 + 1.006X, r = 0.997, eight cut plane). Thus, accurate volume measurement of the ventricular model by 3D echocardiography was confirmed. CONCLUSIONS: Our study demonstrated that 3D echocardiography is highly accurate for volume measurement in a pediatric ventricular model (for volumes of 2 to 50 ml) under static conditions. PMID- 27277976 TI - Usefulness of measurement of carotid arterial wall elasticity distribution in detection of early-stage atherosclerotic lesions caused by cigarette smoking. AB - PURPOSE: The aim of this study was to evaluate early-stage changes in the arterial wall caused by smoking. METHODS: A newly developed real-time ultrasonic measurement system was used to measure the elasticity distribution of the carotid arterial intima-media complex in 53 healthy male volunteers (mean age: 37.6 years), including 27 smokers. Simultaneous measurement of the elasticity distribution and intima-media thickness (IMT) was performed at six locations in the bilateral carotid arteries. RESULTS: The mean elastic modulus in the radial direction (Er) of the carotid arterial area where the IMT was less than 1.1 mm in smokers was larger than that in age-matched nonsmokers. There were no significant correlations between IMT and Er at the same location. However, a significant positive correlation was observed between the maximum IMT (maxIMT) and that of Er (maxEr) in six locations. In smokers, maxEr had a better correlation with the smoking index, and areas of IMT less than 1.1 mm containing harder lesions of Er >= 160 kPa were significantly more frequent than in nonsmokers. CONCLUSION: Measurement of carotid arterial wall elasticity is useful for detecting distortion in the intramural elasticity distribution that occurs prior to IMT thickening caused by smoking as an early-stage atherosclerotic sign. PMID- 27277977 TI - Aging and transmitral flow pattern in patients with systemic hypertension. AB - PURPOSE: Currently, the transmitral flow (TMF) pattern is routinely recorded as the first step in the assessment of left ventricular diastolic function. In young, healthy subjects, it is known that the early diastolic flow (E wave) of TMF is larger than the late diastolic flow (A wave). The E/A ratio then gradually decreases with age. This change in the pattern of TMF can be expected to occur earlier in patients with systemic hypertension than in healthy subjects. However, data pertaining to this matter are limited for Japanese patients. The purpose of this study was to investigate the changing pattern of TMF with age in Japanese patients with systemic hypertension. METHODS: A database of echocardiographic examination reports was surveyed. A total of 553 patients with systemic hypertension (HT group) and 394 patients without hypertension or organic heart disease (control group) were included in this study. The patients were subdivided according to age, after which the E/A ratio was compared for different patient categories and age groups. RESULTS: The E/A ratio gradually decreased with age in the control group, and the mean value of E/A was <1 in the sixth decade. On the other hand, the E/A ratio rapidly decreased and was <1 in the fifth decade in the HT group. CONCLUSION: In patients in the HT group, the E/A ratio decreased about a decade earlier compared with patients in the control group. PMID- 27277978 TI - Predicting prognosis based on the shape of the left ventricular cavity in dilated cardiomyopathy: analysis using rate of improvement in the circle index. AB - PURPOSE: To elucidate the relation between a quantitative measure of the shape of the left ventricular cavity, cardiac function, and prognosis in patients with dilated cardiomyopathy (DCM). METHODS: The hearts of 20 healthy individuals and 18 patients with DCM were evaluated. Participants were aged 48.5 +/- 5.0 years. On the basis of end-systolic four-chamber view echocardiograms, the endocardium of the left ventricle was traced and the resulting curve was segmented using 100 points. A line tangential to the curve was then drawn at each point, and the angle between two adjacent tangential lines was calculated. The deviation of these angles was designated as the circle index. The circle index and hemodynamic findings in patients with DCM were compared, and the rate of improvement in the circle index in these cases of DCM was determined. These patients were then placed into one of two groups: group R (11 patients), those with improvement rates of 10% or higher at time of discharge; and group NR (seven patients), those with rates less than 10%. Diuretic (furosemide) use, New York Heart Association (NYHA) classification, and readmission rate for the two groups were compared 2 years after discharge. RESULTS: The circle index was 2.7 +/- 0.9 in the DCM group and 17.5 +/- 4.2 in the healthy group (P < 0.01). The circle index in the DCM group was correlated with pulmonary capillary wedge pressure (r(2) = 0.42). Use of furosemide was unchanged in group R 2 years after discharge, but had increased for all patients in group NR. All cases in group R were classified as NYHA I 2 years after discharge. In group NR, in contrast, although all cases were classified as NYHA I at discharge, five of seven cases had deteriorated to NYHA III-IV 2 years later and were readmitted to hospital. CONCLUSION: There appears to be a quantifiable correlation between the circularity of the left ventricular cavity and the circle index. This suggests that rate of improvement after treatment for heart failure could predict prognosis in patients with DCM. PMID- 27277979 TI - Relationship between spontaneous echo contrast in the thoracic aorta and plasma von Willebrand factor. AB - PURPOSE: To clarify the relationships between spontaneous echo contrast (SEC) detected by transesophageal echocardiography (TEE) and coagulopathy, ultrasonographic findings that may correlate to biochemical coagulation markers were examined. METHODS: TEE was performed on 49 consecutive patients (mean age 64 +/- 14 years; 28 men, 21 women). Blood samples were taken at the same time as TEE was carried out. Aortic SEC (Ao-SEC) and left atrial SEC (LA-SEC) were classified into three grades: absent, mild and marked. Levels of von Willebrand factor (vWF), thrombin antithrombin III complex (TAT), prothrombin fragments 1+2 (F1+2) and fibrinopeptide A (FPA) were measured. RESULTS: Mean plasma vWF levels by Ao SEC grade were 144 +/- 39% for absent, 177 +/- 55% for mild and 210 +/- 73% for marked, with significantly higher levels in the Ao-SEC marked group than in the Ao-SEC absent group (P < 0.05). Mean plasma vWF levels by LA-SEC were 185 +/- 73% for absent, 180 +/- 49% for mild and 201 +/- 62% for marked, with no significant differences apparent between groups. Moreover, no relationships were identified between Ao-SEC grade and plasma levels of coagulation indicators TAT, F1+2 and FPA. CONCLUSION: Plasma vWF levels correlated to grade of aortic SEC. Characteristics of the coagulation system differ between Ao-SEC and LA-SEC. Ao SEC offers a clinical indicator of platelet thrombus formation. PMID- 27277980 TI - Transabdominal sonographic appearance of adult colonic polyps. AB - PURPOSE: To assess the ability of transabdominal ultrasound to detect adult colonic polyps and to describe their ultrasonographic appearance. METHODS: Total colonoscopy was carried out for 729 consecutive patients over a 39-month period. Ultrasonographic examination of the abdomen was followed by specific examination of the colon. Colorectal ultrasound was carried out for patients with colonic polyps of the protruded type (exclusive of advanced cancers and polyps of the flat or depressed types), and cleansing liquid was administered preparatory to colonoscopic examination. In examining colonic polyps we wanted to determine the sensitivity and specificity of ultrasound for detecting colonic polyps, and the presence of power-Doppler flow signals, location, morphologic classification, and size of the polyps. RESULTS: Ultrasound identified no colonic polyps less than 10 mm in diameter in any of the 729 patients. Of the 732 deternimation (three patients had two polyps greater than 10 mm in diameter), ultrasound yielded a positive diagnosis in 16 cases, false-positive in four cases, false-negative in 40 cases, and negative in 672 cases. Sensitivity of the technique was 28.6% and specificity was 99.4% for detection of polyps greater than 10 mm in diameter. Doppler signals were detected in all positive cases. Most polyps that were false negatives on ultrasound examination occurred in the rectum and sigmoid colon. Sensitivity increased with tumor size, and was as high as 82% (9/11) for polyps exceeding 25 mm in diameter. Fifty-seven percent of pedunculated polyps (type Ip) but no sessile polyps (type Is) were found using ultrasound. CONCLUSION: Colorectal ultrasound detected adult colonic polyps greater than 10 mm in diameter 16 of the 56 in present 729 patients, suggesting that this method may be of limited value in screening for colonic polyps. PMID- 27277981 TI - Establishment of seminars to improve the diagnostic accuracy and effectiveness of breast ultrasound. AB - PURPOSE: To improve the ability of technicians and physicians to find and diagnose breast lesions in breast ultrasound screening. METHODS: Seminars were organized for technicians and physicians engaged in breast ultrasound screening, and tests were carried out to evaluate the usefulness of the seminars. Each seminar lasted 2 days and comprised lectures and group activities. Pretests and post-tests conducted before and after each seminar, respectively, consisted of 100 questions: 50 about animated images, and 50 about static images. The tests required the participant to find lesions in animated images and estimate the probability of malignancy from static images. RESULTS: In the animated image tests, sensitivity was greater after the seminar, although specificity did not change significantly. In the static image tests, sensitivity increased, and a significant increase was also observed in the receiver operating curve analysis for degree of certainty in diagnosing cancer. CONCLUSION: The seminars improved the participants' ability to find and diagnose breast lesions during ultrasound screening. PMID- 27277982 TI - Interventional ultrasound for adrenal masses. AB - PURPOSE: To determine the value of interventional ultrasound (US) for adrenal masses, especially incidentally discovered adrenal masses. METHODS: Demographic, clinical, and pathological data were reviewed for eight patients who underwent percutaneous US-guided puncture or biopsy for adrenal masses from September 1994 through March 2002 in our institute. RESULTS: US-guided intervention was successfully performed for seven patients: two with adrenal cysts, two with adrenocortical adenomas, and three with metastatic adrenal tumors (one from prostate cancer, one from lung cancer, and one from renal cell carcinoma). The remaining patient had bilateral adrenal masses, and a biopsy specimen could not be obtained because safe puncture was difficult. For all patients there was no postoperative hemorrhage or pain, and no major complications were observed during the procedure. CONCLUSIONS: Interventional US using the color Doppler method for adrenal masses is a useful procedure for safe puncture to reveal the orientation of adjacent viscera and blood vessels at the puncture site and to avoid complications including hemorrhage and pneumothorax. US, including color Doppler US, is also useful for detection of complications and follow-up studies because it is noninvasive and can be used for real-time examinations. In addition, pathological examination of specimens obtained by percutaneous biopsy or fine needle aspiration is useful for avoiding unnecessary surgery in patients with metastatic adrenal masses. PMID- 27277983 TI - Isolated gastric varices due to pancreatic cancer. PMID- 27277984 TI - Pancreatic metastasis from lung cancer. PMID- 27277985 TI - Spontaneous ruptured hepatic malignant fibrous histiocytoma. PMID- 27277986 TI - Gallbladder varices. PMID- 27278003 TI - Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss. AB - STUDY QUESTION: In an intent to treat analysis, are clinical outcomes improved in recurrent pregnancy loss (RPL) patients undergoing IVF and preimplantation genetic screening (PGS) compared with patients who are expectantly managed (EM)? SUMMARY ANSWER: Among all attempts at PGS or EM among RPL patients, clinical outcomes including pregnancy rate, live birth (LB) rate and clinical miscarriage (CM) rate were similar. WHAT IS KNOWN ALREADY: The standard of care for management of patients with RPL is EM. Due to the prevalence of aneuploidy in CM, PGS has been proposed as an alternate strategy for reducing CM rates and improving LB rates. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 300 RPL patients treated between 2009 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among two academic fertility centers, 112 RPL patients desired PGS and 188 patients chose EM. Main outcomes measured were pregnancy rate and LB per attempt and CM rate per pregnancy. One attempt was defined as an IVF cycle followed by a fresh embryo transfer or a frozen embryo transfer (PGS group) and 6 months trying to conceive (EM group). MAIN RESULTS AND THE ROLE OF CHANCE: In the IVF group, 168 retrievals were performed and 38 cycles canceled their planned PGS. Cycles in which PGS was intended but cancelled had a significantly lower LB rate (15 versus 36%, P = 0.01) and higher CM rate (50 versus 14%, P < 0.01) compared with cycles that completed PGS despite similar maternal ages. Of the 130 completed PGS cycles, 74% (n = 96) yielded at least one euploid embryo. Clinical pregnancy rate per euploid embryo transfer was 72% and LB rate per euploid embryo transfer was 57%. Among all attempts at PGS or EM, clinical outcomes were similar. Median time to pregnancy was 6.5 months in the PGS group and 3.0 months in the EM group. LIMITATIONS, REASONS FOR CAUTION: The largest limitation is the retrospective study design, in which patients who elected for IVF/PGS may have had different clinical prognoses than patients who elected for expectant management. In addition, the definition of one attempt at conception for PGS and EM groups was different between the groups and can introduce potential confounders. For example, it was not confirmed that patients in the EM group were trying to conceive for each month of the 6-month period. WIDER IMPLICATIONS OF THE FINDING: Success rates with PGS are limited by the high incidence of cycles that intend but cancel PGS or cycles that do not reach transfer. Counseling RPL patients on their treatment options should include not only success rates with PGS per euploid embryo transferred, but also LB rate per initiated PGS cycle. Furthermore, patients who express an urgency to conceive should be counseled that PGS may not accelerate time to conception. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A. TRIAL REGISTRATION DATE: N/A. DATE OF FIRST PATIENT'S ENROLLMENT: N/A. PMID- 27278004 TI - Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell. AB - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which mediate glucose and lipid homeostasis by regulating the expression of a large number of transcription factors. Sphingomyelin synthase (SMS) is a key enzyme in the synthesis of sphingomyelin (SM), and its expression and activity have been reported to be associated with atherosclerosis (AS). Although there have been many functional PPAR and SMS studies on atherosclerosis in recent years, few have investigated the correlation between the activation of PPARdelta and the activity of SMS. In his study, macrophage-induced foam cells were utilized to model important pathological changes that occur in AS. The influence of PPARdelta agonism by GW501516 on SMS and its product molecule SM were measured. Results indicated that the activation of PPARdelta was correlated in a positive manner with the activity of SMS2, and the content of SM was dose dependently increased by GW501516. Together, this study represents the first to suggest that PPARdelta activation may be a potential risk of AS through enhancing activity of SMS2. PMID- 27278005 TI - Neutral endopeptidase and natriuretic peptide receptors participate in the regulation of C-type natriuretic peptide expression in renal interstitial fibrosis. AB - The initiation and progression of renal interstitial fibrosis (RIF) is a complicated process in which many factors may play an activate role. Among these factors, C-type natriuretic peptide (CNP) is an endothelium-derived hormone and acts in a local, paracrine fashion to regulate vascular smooth muscle tone and proliferation. In this study, we established a rat model of unilateral ureteral obstruction (UUO). CNP expression tends to be higher immediately after ligation and declined at later time points, occurring predominantly in tubular epithelial cells. A high-level CNP may contribute to the elevated expression of natriuretic peptide receptor (NPR)-B in the early phase of UUO. However, the sustained expression of NPR-C and neutral endopeptidase (NEP) observed throughout the study period (that is up to 3 months) helps to, at least partly, explain the subsequent decline of CNP. Thus, NEP and NPRs participate in the regulation of CNP expression in RIF. PMID- 27278007 TI - Melancholy about ultrasonography: something is wrong. PMID- 27278006 TI - Downregulation of the PHLDA1 gene in IMR-32 neuroblastoma cells increases levels of Aurora A, TRKB and affects proteins involved in apoptosis and autophagy pathways. AB - We have recently shown that mRNA and protein of PHLDA1 (pleckstrin-homology-like domain family A, member 1) were by far the most upregulated molecules upon treatment of IMR-32 cells with the anti-GD2 ganglioside monoclonal antibody 14G2a. Hence, we decided to study functions of PHLDA1 using human neuroblastoma IMR-32 cells as a model. Here, we show that constitutive expression of mRNA and protein of the PHLDA1 gene in IMR-32 cells was inversely correlated with transcript of the AURKA gene and Aurora A oncoprotein. Next, we silenced PHLDA1 expression in IMR-32 cells using an shRNA interference method. We report that IMR 32 cells with stable downregulation of PHLDA1 showed enhanced cellular ATP levels and an increase in mitochondrial membrane potential, as compared to control and non-transduced cells. We demonstrated that downregulation of PHLDA1 leads to a significant increase in expression of Aurora A and TRKB that are markers of poor prognosis in neuroblastoma. Also, we measured an increase in Aurora A and Akt kinases phosphorylation in the cells. Most importantly, PHLDA1-silenced cells were less susceptible to apoptosis than control cells, as shown by the lower expression of cleaved caspase-3 and PARP as well as a decreased activity of caspase-3 and -7. Our study negatively correlates expression of PHLDA1 and Aurora A in IMR-32 cells and sheds new light on functions of PHLDA1 in the neuroblastoma tumor cells, suggesting its role as a pro-apoptotic protein. Additionally, our results show possible links of the protein to regulation of features of mitochondria and formation of autophagosomes. PMID- 27278008 TI - The current status of contrast-enhanced ultrasound in China. AB - This review article provides an overview of the use of contrast-enhanced ultrasound (CEUS) in China. Currently, the only licensed contrast agent is SonoVue, a sulfur hexafluoride-filled microbubble contrast agent. In combination with a low mechanical index contrast-specific imaging mode, SonoVue-enhanced CEUS can be used to visualize the micro and macro-vasculature continuously. Since 2004, CEUS has been widely used in China in various clinical scenarios. The authors compared CEUS with baseline ultrasound or contrast-enhanced computed tomography with regard to characterization of focal liver lesions (FLLs). On CEUS, heterogeneous or homogeneous hyperenhancement during the arterial phase and washout in the portal/late phase are typical findings for hepatocellular carcinoma. The enhancement features of intrahepatic cholangiocarcinoma, infected FLLs, focal fatty infiltration, focal fatty sparing, complex cystic FLLs, and uncommon benign FLLs were carefully depicted. CEUS was also used for patient selection in ablation therapy and evaluation of response to ablation for liver cancer. The utility of three-dimensional CEUS of the liver was also explored. In non-liver use, CEUS in hilar cholangiocarcinoma, gallbladder, breast, and prostate was initially investigated. In addition, CEUS was used in interventional procedures such as CEUS-guided hemostatic injection, intraoperative CEUS in neurosurgery, and evaluation of response to high-intensity focused ultrasound ablation of uterine fibroids. The Chinese experience has resulted in increased use of CEUS. PMID- 27278009 TI - Mechanical and clinical performance of pulse-inversion tissue harmonic imaging in the superficial region. AB - PURPOSE: To compare image quality between fundamental imaging (FI; transmitted and received frequencies 8.0 and 9.0 MHz, respectively) and pulse-inversion tissue harmonic imaging (PI-THI; transmitted frequencies 4.0 and 4.5 MHz, respectively) within 40 mm of the surface of the probe, we tested axial, lateral, and contrast resolution. METHODS: The axial and lateral resolution were tested by use of a tissue-mimicking test object. For contrast resolution, milk agar blocks of different concentration were used for the comparison test. RESULTS: The lateral resolution was significantly improved by use of PI-THI at a depth of 20 to 40 mm from the surface of the phantom. Axial resolution was not reduced by use of PI-THI compared with FI. The value of the contrast index was higher in PI-THI than in FI. The researchers also evaluated the two modes clinically, by comparing the visibility of 170 cervical lymph nodes (identification of lymph node, echogenic hilus, parenchymal echogenicity). The results revealed significant advantages of PI-THI over FI for three features. CONCLUSION: This study suggests that PI-THI might be mechanically and clinically useful in the superficial region. PMID- 27278010 TI - Clinical experience with newer electronic radial-type endoscopic color Doppler ultrasonography in the diagnosis of esophageal varices. AB - PURPOSE: Endoscopic color Doppler ultrasonography (ECDUS) is a method for obtaining color images of flow in blood vessels. In this study, we report the utility of a newer electronic radial ECDUS for evaluating cases with esophageal varices. METHODS: Nineteen patients with esophageal varices were selected. The ECDUS was performed using a Pentax EG-3670URK (forward-view) with a distal tip diameter of 12 mm. A Hitachi EUB 7500, which provides a 360 degrees view, was used for display. RESULTS: The newer electronic radial ECDUS more clearly delineates images of vessels in patients with esophageal varices. We found two chief advantages over the old probe, i.e., it is easier to manipulate in the distal esophagus than the old probe and it produces 360 degrees images instead of 60 degrees or 270 degrees images. CONCLUSION: Forward-view optics and an extended 360 degrees viewing angle enabled clear color flow images to be obtained from all cases of esophageal varices examined. PMID- 27278011 TI - Ultrasound diagnosis of juvenile forearm fractures. AB - PURPOSE: Metaphyseal forearm fractures are a common pathology in any emergency department. The standard diagnostic procedure is an X-ray of the forearm and wrist. Former studies have shown that these fractures can be visualized by ultrasound. The intention of this study was to evaluate the safety and reliability of the ultrasound diagnostic procedure in comparison with X-ray diagnosis. METHODS: Patients aged 0-12 years with tentative diagnosis of forearm fracture in a physical examination were then examined, from six positions, with a 7.5-MHz linear array transducer. The diagnosis and the recommended treatment were noted, after which standard X-rays were taken. Finally, differences between diagnoses, the extent and direction of the deformity, and the treatment recommended after both diagnostic procedures were analysed. RESULTS: From January 2007 to May 2008, 93 patients were examined. We found 77 fractures in 64 patients (48 radius, 2 physeal fractures of the radius, 1 ulna, and 13 radius and ulna). The sensitivity of ultrasound in diagnosing forearm fractures was 94%, and the specificity was 99%. Difference between the means of the deformities were 1.6 degrees (radius anterior-posterior direction), 1.6 degrees (radius medial lateral direction), 0.2 degrees (ulna anterior-posterior direction), and 0.2 degrees (ulna medial-lateral direction). CONCLUSION: Ultrasound seems to be a valuable and safe alternative to X-ray diagnosis. PMID- 27278012 TI - Calculus detection for ultrasonography using decorrelation of forward scattered wave. AB - PURPOSE: The purpose of this paper is to propose a novel strategy to detect small calculi efficiently. METHODS: The proposed calculus detection strategy focuses on decorrelation of forward scattered waves caused by the failure of Born's approximation. A calculus causes waveform changes of transmit pulses, resulting in a decrease in the cross-correlation coefficients calculated from IQ signals scattered near the calculus position. Therefore, we can detect calculi from the appearance of dips in correlation coefficients. RESULTS: When a calculus exists in a digital tissue map, sharp and deep dips in cross-correlation coefficients between acoustic IQ signals appear around the calculus. By contrast, no apparent dip exists when a tissue map contains no calculus. A scan line interval of 0.2 mm or less is appropriate for the conditions simulated in this paper, and the proper transmit focal range for the proposed method is at a calculus range. CONCLUSION: These results imply that the proposed strategy can improve the efficiency of US devices for small calculus detection. PMID- 27278013 TI - Evaluation of hepatocellular carcinoma with portal vein tumor thrombosis by CEUS before and after hepatic arterial infusion chemotherapy. AB - Hepatocellular carcinoma (HCC) is one of the most common neoplasms worldwide. Portal vein tumor thrombosis (PVTT) is a common complication of advanced HCC, and the prognosis of advanced HCC with PVTT is extremely poor. We report a case of HCC with PVTT evaluated by contrast-enhanced ultrasonography (CEUS) before and after hepatic arterial infusion chemotherapy (HAIC). A 59-year-old man with chronic hepatitis C was admitted to our hospital. CEUS clearly showed the thread and streaks sign in a solid lesion that occupied the right main branch of the portal vein. HAIC was performed, and CEUS after HAIC clearly showed disappearance of the thread and streaks sign. CEUS was very useful in diagnosing PVTT and in evaluating the effectiveness of HAIC in this case. PMID- 27278014 TI - Contrast-enhanced ultrasonography revealed active thoracic bleeding. AB - A 61-year-old woman with a hepatocellular carcinoma located in the subphrenic region was treated by radiofrequency ablation (RFA) under artificial pleural effusion. During RFA, B-mode ultrasonography showed a swirling high echoic lesion in the artificial pleural effusion. A real-time scan performed using contrast enhanced ultrasonography (CEUS) revealed a jet-like extravasation of contrast medium and pooling of microbubbles in the pleural cavity, which were confirmed by angiography. CEUS successfully identified the site of bleeding and can be regarded an effective tool for detecting active bleeding in an emergency. PMID- 27278015 TI - Ultrasonographic findings in isolated superior mesenteric artery dissection. PMID- 27278016 TI - Endoscopic ultrasonographic findings before and after sclerotherapy for gastric varices. PMID- 27278017 TI - Three-dimensional visualisation of soft biological structures by X-ray computed micro-tomography. AB - Whereas the two-dimensional (2D) visualisation of biological samples is routine, three-dimensional (3D) imaging remains a time-consuming and relatively specialised pursuit. Current commonly adopted techniques for characterising the 3D structure of non-calcified tissues and biomaterials include optical and electron microscopy of serial sections and sectioned block faces, and the visualisation of intact samples by confocal microscopy or electron tomography. As an alternative to these approaches, X-ray computed micro-tomography (microCT) can both rapidly image the internal 3D structure of macroscopic volumes at sub-micron resolutions and visualise dynamic changes in living tissues at a microsecond scale. In this Commentary, we discuss the history and current capabilities of microCT. To that end, we present four case studies to illustrate the ability of microCT to visualise and quantify: (1) pressure-induced changes in the internal structure of unstained rat arteries, (2) the differential morphology of stained collagen fascicles in tendon and ligament, (3) the development of Vanessa cardui chrysalises, and (4) the distribution of cells within a tissue-engineering construct. Future developments in detector design and the use of synchrotron X ray sources might enable real-time 3D imaging of dynamically remodelling biological samples. PMID- 27278019 TI - The Rho GTPase Rif signals through IRTKS, Eps8 and WAVE2 to generate dorsal membrane ruffles and filopodia. AB - Rif induces dorsal filopodia but the signaling pathway responsible for this has not been identified. We show here that Rif interacts with the I-BAR family protein IRTKS (also known as BAIAP2L1) through its I-BAR domain. Rif also interacts with Pinkbar (also known as BAIAP2L2) in N1E-115 mouse neuroblastoma cells. IRTKS and Rif induce dorsal membrane ruffles and filopodia. Dominant negative Rif inhibits the formation of IRTKS-induced morphological structures, and Rif activity is blocked in IRTKS-knockout (KO) cells. To further define the Rif-IRTKS signaling pathway, we identify Eps8 and WAVE2 (also known as WASF2) as IRTKS interactors. We find that Eps8 regulates the size and number of dorsal filopodia and membrane ruffles downstream of Rif-IRTKS signaling, whereas WAVE2 modulates dorsal membrane ruffling. Furthermore, our data suggests that Tir, a protein essential for enterohemorrhagic Escherichia coli infection, might compete for Rif for interaction with the I-BAR domain of IRTKS. Based on this evidence, we propose a model in which Rho family GTPases use the I-BAR proteins, IRSp53 (also known as BAIAP2), IRTKS and Pinkbar, as a central mechanism to modulate cell morphology. PMID- 27278020 TI - Diversity in ultrasonics. PMID- 27278018 TI - Sorting nexin 9 negatively regulates invadopodia formation and function in cancer cells. AB - The ability of cancer cells to degrade the extracellular matrix and invade interstitial tissues contributes to their metastatic potential. We recently showed that overexpression of sorting nexin 9 (SNX9) leads to increased cell invasion and metastasis in animal models, which correlates with increased SNX9 protein expression in metastases from human mammary cancers. Here, we report that SNX9 expression is reduced relative to neighboring normal tissues in primary breast tumors, and progressively reduced in more aggressive stages of non-small cell lung cancers. We show that SNX9 is localized at invadopodia where it directly binds the invadopodia marker TKS5 and negatively regulates invadopodia formation and function. SNX9 depletion increases invadopodia number and the local recruitment of MT1-MMP by decreasing its internalization. Together, these effects result in increased localized matrix degradation. We further identify SNX9 as a Src kinase substrate and show that this phosphorylation is important for SNX9 activity in regulating cell invasion, but is dispensable for its function in regulating invadopodia. The diversified changes associated with SNX9 expression in cancer highlight its importance as a central regulator of cancer cell behavior. PMID- 27278021 TI - Effects of cell culture scaffold stiffness on cell membrane damage induced by sonoporation. AB - PURPOSE: As basic studies to realize in vivo sonoporation, rates of cell membrane damage during sonoporation were evaluated using monolayer cells cultured on scaffolds with different degrees of stiffness. METHODS: Four types of scaffolds, constructed using collagen gel, 10 and 30 % acrylamide gels, and a coverslip, were used for cultivation of monolayer cells. Young's moduli measured using an atomic force microscope were in the range 0.09-8.6 kPa for the gel scaffolds, whereas Young's modulus for living cells was 4.5 kPa. Cells with attached microbubbles were exposed to one-shot pulsed ultrasound of 8.0/-1.3 MPa in peak positive/negative pressures with durations of 3, 100, and 10,000 cycles. RESULTS: Cell membrane damage was visualized by fluorescence microscopy using propidium iodide. The 3-cycle ultrasound pulse had no significant effect; however, the rates of damage caused by 100-cycle and 10,000-cycle pulses showed a strong tendency for higher rates of damage with a higher Young's modulus. CONCLUSION: The experimental results indicate that the stiffness of the underlying layer of adherent cells should be considered as an essential parameter of the sonoporation condition and that the optimum exposure conditions for in vivo sonoporation should be determined with consideration of the physical properties of underlying tissues. PMID- 27278022 TI - A micrometer-sized ultrasound contrast agent with nanometer-scale polygonal patterning surfaces. AB - PURPOSE: To develop a smaller micro-sized bubble ultrasound contrast agent which composed of an insoluble, less-dense, self-assembled surfactant with a condensed crystallized nanometer-scale polygonal patterning surface. METHODS: The microbubble was prepared by high-shear mixing a mixture of sucrose esters, glucose sugar, and water. The coulter counter was used to measure the size and concentration of the microbubble. Surface patterns of the microbubble were determined using vitrified samples under cryo-transmission electron microscopy. Myocardial contrast effects of six normal dog's myocardium were assessed. RESULTS: The diameter of the developed microbubble was smaller than Sonovue((r)). Direct imaging of cryo-transmission electron microscopy revealed that the developed microbubble has a nanometer-scale polygonal surface pattern. Both the developed microbubble and Sonovue((r)) effectively enhanced the myocardial contrast. The difference in the peak video intensity, the longevity of the contrast effect, and time-to-peak interval between both microbubbles were not statistically significant (NS). CONCLUSION: The microbubble with nanometer-scale polygonal patterning surfaces is a feasible and promising contrast agent for the ultrasound imaging. PMID- 27278023 TI - In vitro experiment using porcine artery for evaluation of ultrasonic measurement of arterial luminal surface profile. AB - INTRODUCTION: In early-stage atherosclerosis, the luminal surface of the arterial wall becomes rough because of detachment of endothelial cells and degeneration of the internal elastic layer. Therefore, it would be useful if minute luminal surface roughness of the carotid arterial wall, which occurs in the early stage of atherosclerosis, could be measured noninvasively with ultrasound. The injured luminal surface is believed to have roughness of a few hundred micrometers. However, in conventional ultrasonography, the axial resolution of a B-mode image depends on the ultrasonic wavelength (150 MUm at ultrasonic center frequency of 10 MHz) because a B-mode image is constructed using the amplitude of the RF echo signal. Therefore, such surface roughness cannot be measured accurately from a conventional B-mode image. Recently, we successfully measured such minute surface profile transcutaneously using the phase shift of an ultrasonic echo from the carotid arterial wall. In our previous validation experiment, a silicone phantom with minute surface roughness of 10-20 MUm was measured. However, the feasibility of our proposed method has never been validated using biological tissues. MATERIALS AND METHODS: In the present study, luminal surface roughness of a porcine artery was measured and the result was evaluated by comparing it with the result measured using a stylus profilometer. RESULTS AND CONCLUSION: The root mean squared difference between the surface roughness measured by ultrasound and the stylus profilometer was 10.5 MUm. This result proves that our proposed method can be used to measure minute surface roughness of biological tissue. PMID- 27278024 TI - Evaluation of whether the ultrasonographic onion skin sign is specific for the diagnosis of an appendiceal mucocele. AB - PURPOSE: To evaluate whether the onion skin sign on ultrasonography (US) of the lower abdomen is specific for the diagnosis of an appendiceal mucocele. METHODS: Our study included 231 lesions from 229 patients in whom transabdominal US detected lesions in the lower abdomen and who had definitive pathological diagnoses in the small bowel, ileocecal valve, cecum, appendix, mesentery, adnexa uteri or pelvic cavity outside the major organs. Patients with metastatic tumors were excluded. We reviewed the reports and images from transabdominal US and checked for the presence of the onion skin sign. The sensitivity, specificity, and accuracy of the sign for the diagnosis of an appendiceal mucocele were calculated. RESULTS: Five (2.2 %) of the 231 lesions showed the onion skin sign on US and all were diagnosed with an appendiceal mucocele. The sensitivity, specificity, and accuracy of the sign for the diagnosis of an appendiceal mucocele were 63, 100, and 99 %, respectively. CONCLUSIONS: The onion skin sign in the lower abdomen appears to be specific for the diagnosis of an appendiceal mucocele. In cases where the onion skin sign is obviously present in the lower abdomen on US, an appendiceal mucocele should be considered as the leading diagnosis. PMID- 27278025 TI - Acoustic structure quantification (ASQ): a new tool in sonographic examination of liver lesions in hepatic alveolar echinococcosis. AB - PURPOSE: Qualitative and quantitative acoustic structure quantification (ASQ) is a new, noninvasive sonographic imaging method based on B-mode. This prospective clinical pilot study aims to answer the question whether delineation and measurement of liver lesions in hepatic alveolar echinococcosis (HAE) can be improved by ASQ. Furthermore, this is the first pilot study to explore how ASQ parameters in HAE lesions develop. METHODS: A total of 24 patients (male = 13/female = 11, mean age = 52 years (16-85), mean disease duration = 68 months (1 334)) with HAE were examined with ASQ using a Toshiba Aplio 500 unit. ASQ parameters were measured in HAE liver lesions and in adjacent non-tumor parenchyma. Quantitative analysis was performed offline using ASQ quantification software. RESULTS: Subjectively parasitic tumors in HAE appear more prominent in color-coded ASQ imaging, but the size of lesions measured in ASQ mode does not differ from size measurements in B-mode. Median focal disturbance ratio (FD ratio) in lesions was 3 (0.1-3), compared with 0.5 (0.1-1.8) in surrounding liver parenchyma (p < 0.0001). Statistical comparison of other ASQ parameters (mode, average, standard deviation) shows results that are similarly significant with p values between p < 0.0001 and p < 0.0018. CONCLUSION: ASQ is a promising sonographic method for examination and quantification of structural changes of liver parenchyma in HAE lesions. PMID- 27278026 TI - Real-time tissue elastography (RTE) for noninvasive evaluation of fibrosis in liver diseases in children in comparison to liver biopsy. AB - PURPOSE: To determine the value of real-time tissue elastography (RTE) in pediatric liver diseases in comparison to liver biopsy. METHODS: RTE was performed on 34 patients (?, n = 17; ?, n = 17; range 0-21 years) with various acute and chronic liver diseases: autoimmune hepatitis (n = 5), liver transplantation (n = 5), Wilson's disease (n = 4), hepatopathy of unknown origin (n = 4), unclear cholestatic hepatitis (n = 2), thalassemia major (n = 2), glycogenosis (n = 2), hereditary fructose intolerance (n = 1), alpha-1 antitrypsin deficiency (n = 1), diabetes mellitus type 1 (n = 1), chronic intestinal pseudo-obstruction (n = 1), primary sclerosing cholangitis (n = 1), hepatitis B (n = 1), cirrhosis of unknown origin (n = 1), drug-induced hepatopathy (n = 1), unexplained transaminase elevation (n = 1), and nonalcoholic steatohepatitis (n = 1). Included children were biopsied. RTE was performed on a control group (n = 30; ?, n = 15; ?, n = 15). The mean value of strain (MEAN) in arbitrary units and the ratio of blue color-coded harder tissue (AREA) were calculated based on an elasticity histogram of the selected region of interest in liver parenchyma. They were compared with the histologically defined grade of liver fibrosis. RESULTS: In comparison to the scoring systems, a moderate correlation was observed for MEAN and AREA by excluding the F0 patients [MEAN r = -0.575 to -0.645, AREA r = 0.545-0.607 (p < 0.05)]. Differentiation of the control group and low-grade fibrosis (F1) from high-grade fibrosis (F2-4) was significantly possible (p values <0.001 at 5 % significance level). CONCLUSION: RTE parameters enable a possible differentiation of high fibrosis; however, their correlation with fibrosis stage was moderate. RTE seems to be a promising method in liver fibrosis grading in children. PMID- 27278027 TI - Relationship between detection of the cervical gland area during the late third trimester and necessity for induction of labor to prevent post-term delivery. AB - OBJECTIVES: With the maturation of the cervical canal during pregnancy, the cervical gland area (CGA) as observed on transvaginal ultrasonography is gradually obscured. The aim of this study was to elucidate the significance of CGA in the late third trimester as a determinant of the outcome of labor. METHODS: We investigated 123 primiparous women with singleton pregnancies at 36 41 weeks' gestation. The women were divided into two groups: a normal delivery group (93 women), which had vaginal delivery without medical intervention, and an induction of labor group (30 women), which required induction of labor after 41 weeks and 0 day. At outpatient prenatal checkups, the Bishop score (BS) was assessed by pelvic examination, and cervical length (CL) and CGA were evaluated by transvaginal ultrasonography. The relationship between each parameter and induction of labor was retrospectively determined and compared. RESULTS: Time dependent assessment of each outcome determinant showed that the CGA detection rate was higher and the CL was longer in the induction of labor group from 3 weeks to 1 week before delivery at a significant level (P < 0.05); however, the BS was significantly lower in the induction of labor group only at 1 week before delivery (P < 0.05). When multiple logistic regression analysis of the necessity of induction of labor was conducted using BS, CL, and CGA parameters as explanatory variables at 1 week before delivery, CGA alone was shown to be an independent predictor of induction of labor (OR = 6.1, 95 % CI 2.3-16.2). CONCLUSION: The present study suggests that in the late third trimester, evaluation of CGA with transvaginal ultrasonography is most useful in predicting the necessity of induction of labor to prevent post-term delivery. PMID- 27278028 TI - Accuracy of the sonographic fat pad sign for primary screening of pediatric elbow fractures: a preliminary study. AB - PURPOSE: The purpose of this study was to evaluate the diagnostic accuracy of the sonographic fat pad sign (FPS) as a predictor for pediatric elbow fractures. PATIENTS AND METHODS: This is a prospective study of children under 14 years with suspected elbow fractures. All participants underwent at first ultrasonography focused on a FPS followed by standard elbow radiographs. US findings were compared to final fracture diagnosis. RESULTS: 38 out of 79 children had an elbow fracture. A sonographic FPS predicted an elbow fracture with a sensitivity/specificity of 97.3/90.5 %, positive/negative likelihood ratios (LR) were 10.2/0.03 and correct/false classification rates were 93.7/6.3 %. Primary US findings were later reviewed by a blinded physician giving a congruity of 96.2 %. These secondary US findings predicted an elbow fracture with a sensitivity/specificity of 92.1/92.7 %, positive/negative LRs were 12.6/0.09 and correct/false classification rates were 92.4/7.5 %. CONCLUSION: The sonographic FPS could serve as a useful screening tool in primary evaluation of pediatric elbow injuries. If a fracture is unlikely after clinical and US evaluation, additional radiographs are dispensable, thereby potentially minimizing the radiation burden in childhood and reducing the length of stay in the Emergency Department. PMID- 27278029 TI - Reliability of peripheral intraneural microhemodynamics evaluation by using contrast-enhanced ultrasonography. AB - PURPOSE: The purpose of the study was to validate the reliability of quantitative intraneural enhancement patterns by using contrast-enhanced ultrasonography (CEUS). METHODS: Nine asymptomatic wrists underwent a total of three CEUS examinations each conducted at 1-month intervals. The CEUS enhancement pattern of median nerves was quantitatively evaluated. The area under the time-intensity curve was calculated by placing the regions of interest at the proximal, center, and distal regions of the median nerve. An intra-class correlation coefficient for intra-observer, inter-observer, and inter-examination reproducibility was calculated. RESULTS: The intra- and inter-observer reproducibility was almost perfect. Inter-examination reproducibility of the proximal, center, and distal regions was 0.891, 0.614, and 0.535, respectively. In this study, we found that the reproducibility of the distal and center regions of the median nerve in the carpal tunnel was lower than that of the proximal region. CONCLUSION: High intra observer, inter-observer, and inter-examination reproducibility of CEUS was obtained in the evaluation of the intraneural enhancement pattern when the region of interest was placed in the proximal region of the median nerve. PMID- 27278030 TI - Carcinosarcoma, an atypical subset of gallbladder malignancies. AB - Carcinosarcoma represents an atypical subset of gallbladder malignancies, and sonographic imaging features have not yet been precisely defined. Previously reported cases have shown a heterogeneously echogenic solid mass protruding into and filling the gallbladder lumen. We present herein a case of carcinosarcoma and propose another finding suggestive of this tumor. The patient was a woman in her 70s. Abdominal sonography revealed that the gallbladder lumen was half-filled by a large mass (maximum diameter, 68 mm) showing heterogeneous echogenicity slightly higher than that of bile. However, despite the large size of the mass, gallbladder shape was well-preserved. Considering the findings on computed tomography, cholecystectomy was performed under a diagnosis of gallbladder malignancy. Pathological examination revealed two types of malignant histology: a sarcomatous element of malignant spindle cells and a carcinomatous element of adenocarcinoma tissue. Foci of malignant cartilage and bone areas were also found sporadically. Accompanied by immunohistochemical examination, the mass was diagnosed as carcinosarcoma. The present case showed somewhat different imaging findings from those of ordinary gallbladder carcinoma. Carcinosarcoma should be considered when a well-preserved shape of the gallbladder is recognized along with protrusion of a large heterogeneously echogenic mass into and filling the gallbladder lumen. PMID- 27278032 TI - Prenatal ultrasound findings and a new ultrasonographic sign of epidermolysis bullosa with congenital pyloric atresia: a report of three cases. AB - Epidermolysis bullosa with pyloric atresia (EB-PA) is a rare autosomal recessive disease that is characterized by fragility of the skin and mucous membranes. The course of EB-PA is usually severe and often lethal in the neonatal period. In most cases, prenatal diagnosis of this syndrome is considered in pregnancies at risk for recurrence. EB-PA can be described during pregnancy with sonographic signs such as polyhydramnios with a dilated stomach, the "snowflake sign", which are echogenic particles in the amniotic fluid, and several other anomalies. In this report, we present three cases of EB-PA suggested by the results of prenatal sonography, and describe a new ultrasonographic sign, i.e., complete chorioamniotic membrane separation, which can be helpful for the diagnosis. The prenatal diagnoses were confirmed postnatally. Two of the three cases had no family history, and one of these two cases was the product of a non consanguineous couple. PMID- 27278031 TI - Three-dimensional high-definition flow in the diagnosis of placental lakes. AB - Placental lakes are sonolucent areas often found in the normal placenta. Most of them are asymptomatic. They are sometimes related to placenta accreta or intrauterine fetal growth restriction, among other conditions. Although Doppler sonography is useful for evaluating noxious placental lakes, it is not easy to adapt Doppler studies to conventional two-dimensional color Doppler sonography because of the low-velocity blood flow and high vascularity in the placenta. Here, we demonstrate how three-dimensional high-definition imaging of flow provides a novel visual depiction of placental lakes, which helps substantially with the differential diagnosis. As far as we know, there have been no previous reports of observation of placental lakes using three-dimensional high-definition imaging of flow. PMID- 27278033 TI - Conservative management after prenatal ultrasound diagnosis of meconium periorchitis. AB - Meconium periorchitis is caused by the leakage of meconium from a bowel perforation into the peritoneal cavity via a patent processus vaginalis into the scrotal sac during fetal life or in the early postnatal period. Intrauterine meconium peritonitis causes sterile inflammatory response and calcification. Here, we describe a prenatally diagnosed case of meconium periorchitis. During the ultrasound scan at 29 weeks' gestation, enlargement of the scrotum with many small hyperechogenic masses and normal anatomy of testis was observed. Our case is the 11th prenatally diagnosed case presented in the worldwide literature and the first one described in Poland. This case confirms the latest tendency for the conservative management of meconium periorchitis and an asymptomatic postnatal course. PMID- 27278034 TI - HDlive and HD-flow images of early-stage nonhydropic mole. AB - We present our first experience of constructing an image of an early-stage complete hydatidiform mole employing HDlive. Conventional 2D sonography showed massive, lobulated, and mixed masses and intrauterine anechoic fluid collection. Smooth, lobulated masses were clearly recognized using HDlive. Small, irregular, cystic spaces inside the masses were also evident. HDlive provided anatomically realistic features akin to macroscopic specimens for physicians and pathologists, owing to the complete depiction of the inner surface of an early-stage nonhydropic mole. PMID- 27278035 TI - HDlive imaging of fetal enteric duplication cyst. AB - Enteric duplication cysts are rare congenital anomalies, but their antenatal diagnosis is becoming more common because of advances in ultrasonography. With the latest state-of-the-art technology, HDlive facilitates a more realistic anatomical visualization of different fetal organ structures, making diagnosis more precise. We present a case of antenatal HDlive imaging of an enteric duplication cyst. A 26-year-old pregnant Japanese woman was referred to our ultrasound clinic because of a fetal intra-abdominal cyst at 27 weeks of gestation. Two-dimensional (2D) ultrasound revealed a sonolucent, ellipsoid structure in the subhepatic area. Magnetic resonance imaging yielded the same findings. However, irregular internal echoes appeared at 33 weeks of gestation. There was no vascularity on color Doppler. HDlive clearly depicted a more realistic image of the circular mass, which was thick walled, with a large amount of debris inside, and showed no communication with adjacent structures. Careful monitoring was conducted for these unusual findings. A day after delivery, an emergency operation was performed because the infant had sudden signs and symptoms of obstruction. Intra-operative findings were ileus and a necrotic ileal duplication cyst confirmed by histopathologic studies. Complications of enteric duplication cyst can arise at any time of life, and so thorough monitoring may be recommended. The findings of irregular internal echoes and a large amount of debris inside the cyst are relatively characteristic features of a complicated cyst. HDlive gives us additional information on the actual appearance of a complicated cyst that may be difficult to obtain using conventional 2D sonography alone. HDlive can be very useful in the antenatal surveillance of enteric duplication cysts. PMID- 27278036 TI - Prenatal diagnosis of type 1 fibular hemimelia. AB - Fibular hemimelia (FH) is a congenital longitudinal limb deficiency characterized by complete or partial absence of the fibula. Typically, it has been diagnosed at birth, when the neonate is seen to have lower limb shortening and a foot with missing toes. Although it is the most frequent lower limb deficiency anomaly, there are few published reports of prenatally diagnosed cases. Most of these published cases have involved the complete absence of the fibula, which is relatively easy to diagnose with antenatal ultrasound. In our opinion, our case is the first case of unilateral partial absence of the fibula detected using prenatal ultrasound imaging. Herein, we report a FH case associated with foot equinovalgus, and absence of the fourth and fifth foot rays diagnosed at 24 weeks' gestation. The anomaly was confirmed after birth by X-ray, and conservative orthopedic management was chosen. Our case shows that partial limb defects can also be detected by prenatal ultrasound imaging. PMID- 27278037 TI - HDlive imaging of vertical, bridging uterine synechia during pregnancy. AB - We present a case of vertical, bridging uterine synechia in the central part of the uterine cavity diagnosed by conventional two-dimensional (2D) sonography and HDlive at 29 weeks and 5 days of gestation. 2D sonography showed a uterine synechia located vertically in the central part of the uterine cavity, dividing the lower uterine cavity into two parts. HDlive clearly revealed triangular, vertical, and bridging uterine synechia with foot protrusion and umbilical cord prolapse in the lower uterine cavity. The low, liquor-filled amniotic cavity was divided by a thin membrane. MRI confirmed the vertical structure dividing the uterus with umbilical cord prolapse. Emergency cesarean section was performed at 37 weeks and 1 day of gestation because of onset of labor, and a female infant weighing 2,380 g was delivered with an umbilical artery pH of 7.25, and Apgar score of 6/9 at 1 and 5 min, respectively. The vertical, bridging synechia in the central part of uterine cavity was confirmed during the operation. PMID- 27278038 TI - A case of reocclusion of the renal artery diagnosed by the color Doppler method with evaluation of blood flow direction in the collateral circulation of the kidney in addition to the non-detectable blood signal in the renal artery. AB - A 23-year-old woman was referred to our hospital for an interventional procedure for chronic total occlusion of the right renal artery, probably due to fibromuscular dysplasia (FMD), and for control of renal vascular hypertension. Before percutaneous transluminal renal angioplasty (PTRA), aortography revealed collateral circulation to the right kidney from the lower lumbar artery. After PTRA, however, blood flow in the renal side of the collateral circulation flowed outside from the right renal parenchyma. 4 months later, we could not find a blood flow signal in the right renal artery, and there was a contrary flow signal in the right kidney parenchyma continuously from the extrahilar vessel, possibly a collateral artery. These findings indicated reocclusion of the right artery. We confirmed reocclusion of the renal artery and collateral feeding by contrast dynamic computed tomography (CT), and PTRA was performed again without any complications or reocclusion for 5 months. This is the first case report showing that a back-flowing signal in the right renal parenchyma from the extrahilar artery is useful as an indirect finding suggesting reocclusion. PMID- 27278039 TI - Assessment of irreversible electroporation ablation zone using Kupffer-phase contrast-enhanced ultrasound images with Sonazoid. PMID- 27278040 TI - Observation of the interureteric ridge and ureteral orifice in a patient with a cystocele using color Doppler ultrasonography via the prolapsed bladder. PMID- 27278042 TI - Editor's note. PMID- 27278041 TI - Standard method for ultrasound evaluation of aortic and peripheral arterial lesions. PMID- 27278043 TI - Acknowlegment to reviewers. PMID- 27278044 TI - Modified nonlinear complex diffusion filter (MNCDF). AB - BACKGROUND: Speckle noise removal is the most important step in the processing of echocardiographic images. A speckle-free image produces useful information to diagnose heart-related diseases. Images which contain low noise and sharp edges are more easily analyzed by the clinicians. This noise removal stage is also a preprocessing stage in segmentation techniques. METHODS: A new formulation has been proposed for a well-known nonlinear complex diffusion filter (NCDF). Its diffusion coefficient and the time step size are modified to give fast processing and better results. An investigation has been performed among nine patients suffering from mitral regurgitation. Images have been taken with 2D echo in apical and parasternal views. RESULTS: The peak signal-to-noise ratio (PSNR), universal quality index (Qi), mean absolute error (MAE), mean square error (MSE), and root mean square error (RMSE) have been calculated, and the results show that the proposed method is much better than the previous filters for echocardiographic images. CONCLUSIONS: The proposed method, modified nonlinear complex diffusion filter (MNCDF), smooths the homogeneous area and enhances the fine details. PMID- 27278045 TI - A novel global strain diastolic index correlates with plasma NT-proBNP levels in asymptomatic hypertensive patients with preserved left ventricular ejection fraction. AB - BACKGROUND: The strain imaging diastolic index (SI-DI) was reported to be a sensitive marker of regional left ventricular (LV) delayed relaxation induced by ischemia. However, the clinical usefulness of the global SI-DI has not been evaluated. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic diastolic LV dysfunction. This study investigated the ability of a novel parameter, the global SI-DI, obtained using 2D speckle tracking imaging (2DSI) to correlate with the plasma NT-proBNP levels in asymptomatic hypertensive patients with preserved LV ejection fraction. METHODS: We performed 2D echocardiography and 2DSI in 83 asymptomatic hypertensive patients with preserved ejection fraction (>45 %) and in 37 control subjects. In 2DSI, the LV longitudinal peak strain and the SI-DI of 18 LV segments were measured. NT-proBNP was measured in all subjects. The data were compared between hypertensive patients and normal controls. RESULTS: The average peak strain and global SI-DI of 18 LV segments were significantly reduced in hypertensive patients compared with control subjects (P < 0.05); however, only the global SI-DI was significantly correlated with log10 NT-proBNP (r = -0.469, P = 0.001). In Pearson's correlation analyses, log10 NT-proBNP was significantly correlated with E/e', E/A ratio, early diastolic mitral annular velocity (e'), global peak strain, deceleration time of the E-wave, and LV ejection fraction. In the multiple stepwise regression analysis, the global SI-DI was the strongest independent determinant of log10 NT-proBNP (beta = -0.386, P = 0.008). CONCLUSIONS: The global SI-DI derived from 2DSI correlates well with plasma NT proBNP levels and may have prognostic value in asymptomatic hypertensive patients with preserved ejection fraction. PMID- 27278046 TI - Left atrial appendage occlusion device-related thrombus: a case report and review of the literature. AB - A 75-year-old male with persistent atrial fibrillation underwent implantation of a left atrial occlusion device. After 6 weeks, a scheduled trans-esophageal echocardiogram showed a 1.1-cm * 1.1-cm mass within the occluded left atrial appendage, suspected to be thrombus. He was continued on warfarin for an additional 6 weeks and a repeat trans-esophageal echocardiogram showed obliteration of the left atrial appendage. This report describes an uncommon observation detected at scheduled follow up by trans-esophageal echocardiogram, which sheds some light on the mechanism by which this device "matures" after it is implanted inside the left atrial appendage. PMID- 27278047 TI - Endophthalmitis as a first manifestation of right-sided endocarditis in a patient with patent foramen ovale. AB - Endogenous endophthalmitis is a rare complication of endocarditis, rendering poor visual prognosis. We report a case of a 66-year-old female with renal failure who presented with fever, ocular pain, and purulent eye discharge. After a diagnosis of endogenous endophthalmitis, she was treated with antibiotics and enucleation of the eye. Due to persistent fever and positive blood cultures, a transesophageal echocardiography was undertaken, disclosing a large mural vegetation in the right atrium, catheter-associated vegetations, and a patent foramen ovale. Endocarditis is an uncommon source of endogenous endophthalmitis, and has rarely been associated to right-sided endocarditis and paradoxical septic embolization. PMID- 27278048 TI - A case of significantly increased mitral regurgitation early after atrial septal defect closure. AB - We report a rare case in which mitral regurgitation (MR) was exacerbated to a severe level early after atrial septal defect (ASD) closure, even though the female patient had preoperatively mild MR and mild changes in mitral valve (MV) and sinus rhythm. The mechanism of increased MR was considered as poor coaptation and tethering of the MV due to the restricted motion of the posterior leaflet in addition to geometric changes of the left ventricle (LV) after ASD closure. PMID- 27278049 TI - Left main coronary artery origin from the right coronary sinus: rare, dangerous, and easy to miss on routine transoesophageal echocardiography. PMID- 27278050 TI - Left ventricular undulation in a patient with atrial flutter. PMID- 27278051 TI - Biatrial thrombus across a patent foramen ovale with fatal pulmonary and coronary embolism. PMID- 27278052 TI - Parachute-like mass at the superior vena cava occurring after diagnostic right heart catheterization evaluated with real-time three-dimensional transesophageal echocardiography. PMID- 27278053 TI - Giant left atrial thrombus caused by direct invasion of lung cancer. PMID- 27278055 TI - Cooperativity of intermolecular hydrogen bonds in microsolvated DMSO and DMF clusters: a DFT, AIM, and NCI analysis. AB - Density functional theory (DFT) calculations are performed to study the hydrogen bonding in the DMSO-water and DMF-water complexes. Quantitative molecular electrostatic potential (MESP) and atoms-in-molecules (AIM) analysis are applied to quantify the relative complexation of DMSO and DMF with water molecules. The interaction energy of DMSO with water molecules was higher than in DMF-water complexes. The existence of cooperativity effect helps in the strong complex formation. A linear dependence was observed between the hydrogen bond energies EHB, and the total electron densities in the BCP's of microsolvated complexes which supports the existence of cooperativity effect for the complexation process. Due to the stronger DMSO/DMF and water interaction, the water molecules in the formed complexes have a different structure than the isolated water clusters. NCI analysis shows that the steric area is more pronounced in DMF-water complex than the DMSO-water complex which accounts for the low stability of DMF water complexes compared to the DMSO-water complex. Graphical abstract NCI analysis shows that the steric area is more pronounced in DMF-water complex than the DMSO-water complex which accounts for the low stability of DMF-water complexes compared to the DMSO-water complex. PMID- 27278056 TI - Does radiofrequency ablation (RFA) epiphysiodesis affect adjacent joint cartilage? AB - PURPOSE: To test the hypothesis that epiphysiodesis made with radiofrequency ablation (RFA) is a safe procedure that disrupts the growth plate without damaging the adjacent joint articular cartilage. METHODS: RFA epiphysiodesis was done during 8 min in vivo in 40 growing pig tibia physis. In addition, three tibiae were ablated for 16 min and three more for 24 min. As a burned cartilage reference, six tibiae were ablated on the joint articular cartilage for 8 min. After the procedure, the animals were terminated and the tibiae were harvested. Magnetic resonance imaging (MRI) was done ex vivo to evaluate the joint articular cartilage in all samples. We used T1-weighted, T2-weighted, and water content sequences under a 1.5 T magnetic field. RESULTS: On the burned articular cartilage, intensity changes were observed at MRI. We found no evidence of articular cartilage damage on the 40 8-min RFA procedures. The tibiae ablated for 16 min and 24 min showed intact joint cartilage. CONCLUSIONS: Epiphysiodesis using RFA is safe for the adjacent articular cartilage. This study shows that RFA can be done safely in the growing physis of pigs, even with triple duration procedures. PMID- 27278054 TI - Head-to-Head Comparison of Aripiprazole and Risperidone in the Treatment of ADHD Symptoms in Children with Autistic Spectrum Disorder and ADHD: A Pilot, Open Label, Randomized Controlled Study. AB - BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are frequently overlapping neurodevelopmental disorders. Individuals in whom the disorders are comorbid show more severe impairment because of deficits in the processing of social situations, adaptive functioning, and executive control than individuals with either disorder alone. OBJECTIVE: This open-label pilot study aimed to evaluate and compare the efficacy and tolerability of risperidone and aripiprazole for treating ADHD symptoms in patients with both ASD and ADHD over the course of 24 weeks of treatment. METHODS: Patients (n = 44) were randomly assigned to start treatment with risperidone (22 patients) or aripiprazole (22 patients). Children were evaluated before starting treatment (T0), and after 12 weeks (T1) and 24 weeks (T2) of treatment. At each visit, specific psychiatric clinical scales were administered to assess the efficacy of the two drugs. RESULTS: The mean age was 8.4 +/- 2.9 years in the aripiprazole group and 7.8 +/- 2.3 years in the risperidone group. A total of 37 children (29 boys and 8 girls) completed the study (18 in the aripiprazole group and 19 in the risperidone group). Aripiprazole and risperidone appeared to have similar benefits in terms of efficacy and tolerability, although there were slight differences between the two drugs. Both groups showed a significant improvement in ADHD symptoms after 24 weeks of treatment (ADHD Rating Scale, Conners Parent Rating Scale-Hyperactivity, and Clinical Global Improvement Severity Scale). No significant difference between the two drugs on any parameters at 24 weeks were found. Prolactin levels were decreased in the aripiprazole group. Both drugs were well tolerated, with no serious adverse events detected. CONCLUSIONS: Our study confirms the efficacy of both aripiprazole and risperidone in ameliorating ADHD symptoms of children also presenting with ASD. PMID- 27278057 TI - Synchronized and controlled release of metformin hydrochloride/glipizide from elementary osmotic delivery. AB - The combination of metformin hydrochloride (MTF) and glipizide (GLZ) is second line medication for diabetes mellitus type 2 (DMT2). In the present study, elementary osmotic pump ( EOP) tablet is designed to deliver the combination of MTF and GLZ in a sustained and synchronized manner. By analyzing different variables of the formulation, sodium hydrogen carbonate is introduced as pH modifier to improve the release of GLZ, while ethyl cellulose acts as release retardant to reduce the burst release phase of MTF. A two-factor, three-level face-centered central composite design (FCCD) is applied to investigate the impact of different factors on drug release profile. Compared with conventional tablets, the EOP tablet demonstrates a controlled release behavior with relative bioavailability of 99.2% for MTF and 99.3% for GLZ. Data also shows EOP tablet is able to release MTF and GLZ in a synchronized and sustained manner both in vitro and in vivo. PMID- 27278058 TI - [Spontaneous intracranial hypotension and Marfan syndrome]. AB - Spontaneous intracranial hypotension is the most common complication in patients undergoing a lumbar puncture. A much rarer entity is headaches attributed to spontaneous (or idiopathic) low cerebrospinal fluid (CSF) pressure but the combination with a connective tissue disorder is even rarer. The first case of a patient with spontaneous intracranial hypotension and genetically established Marfan syndrome was published in 1995. This article describes the cases of two female patients who presented with postural headache. Magnetic resonance imaging revealed multiple leakages of CSF and both patients had a genetically confirmed diagnosis of Marfan syndrome. The initial symptomatic treatment did not result in a significant relief of the headaches. Epidural blood patching was performed and the intervention was successful in both patients. Finally, the most important epidemiological, diagnostic and pathophysiological aspects are demonstrated and the therapeutic procedures are presented. PMID- 27278059 TI - [Pharmacological prophylactic treatment for relapse of alcohol dependence : Results of current meta-analyses]. PMID- 27278060 TI - Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver. AB - Sodium taurocholate cotransporting polypeptide (NTCP) is a recently discovered hepatitis B virus (HBV) receptor. In the present study, we used TK-NOG mice with a humanized liver to examine the impact of endogenous NTCP expression on HBV infection. Upon inoculation with HBV, these mice exhibited clear viremia in 2 weeks, and serum HBV DNA levels gradually increased. The frequency of HBsAg positive hepatocytes in the liver was 5.1 +/- 0.6% at 2 weeks and increased with increasing HBV DNA levels, reaching 92.9 +/- 2.8% at 10 to 12 weeks. In vivo siRNA-mediated NTCP knockdown before and after HBV inoculation significantly suppressed the levels of HBV replication and the frequency of HBsAg-positive hepatocytes at 2 weeks, whereas NTCP knockdown 13 weeks after infection did not affect these parameters. Similar to the humanized mouse livers in the early phase of HBV infection, human liver samples from chronic hepatitis B patients, especially those treated with nucleos(t)ide analogues, contained a considerable number of hepatocytes that were negative for the anti-HBs antibody. In conclusion, NTCP inhibition prevents the spread of HBV-infected hepatocytes in mice with a humanized liver. NTCP-targeted therapy has potential for regulating HBV infection in patients with chronic hepatitis B. PMID- 27278061 TI - Food variety consumption and household food insecurity coping strategies after the 2010 landslide disaster - the case of Uganda. AB - OBJECTIVE: To evaluate the nutritional situation of the victims of the 2010 landslide disaster in Uganda, food varieties consumed and coping strategies were assessed. DESIGN: Cross-sectional. Food variety scores (FVS) were obtained as the total of food items eaten over the last week while an index was based on severity weighting of household food insecurity coping strategies. We included 545 affected and 533 control households. SETTING: Victims in the affected Bududa district in Eastern Uganda and those victims resettled in the Kiryandongo district, Western Uganda. RESULTS: Adjusted for covariates, in Bududa significantly higher mean FVS were observed among: affected than controls; farmers than others; and relief food recipients. Control households scored higher means (se) on severity of coping: 28.6 (1.3) v. 19.2 (1.2; P<0.01). In Kiryandongo, significantly higher FVS were observed among: control households; household heads educated above primary school; those with assets that complement food source; and recipients of relief food. Severity of coping was significantly higher among affected households and non-recipients of relief food. Affected households had a higher likelihood to skip a day without eating a household meal in Bududa (OR=2.31; 95 % CI 1.62, 3.29; P<0.01) and Kiryandongo (OR=1.77; 95 % CI 1.23, 2.57; P<0.01). CONCLUSIONS: Whereas FVS and severity of coping showed opposite trends in the two districts, resettlement into Kiryandongo led to severe coping experiences. Administrative measures that provide a combination of relief food, social protection and resettlement integration may offset undesirable coping strategies affecting diet. PMID- 27278062 TI - Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation on gait kinematics in Parkinson's disease: a randomized, blinded study. AB - Gait dysfunction in Parkinson's disease (PD) does not always respond to bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Since right hemisphere motor networks may be dominant for gait control, identical stimulation of asymmetric circuits could account for gait dysfunction. We compared the effects of bilateral and unilateral STN-DBS on gait kinematics in PD patients who developed gait impairment after STN-DBS. Twenty-two PD patients with >50 % improvement in motor scores, but dopamine-resistant gait dysfunction 6-12 months after bilateral STN-DBS were blindly tested off dopaminergic effects in four randomly assigned DBS conditions: bilateral, right-sided, left-sided and off stimulation. Motor scores (MDS-UPDRS III), gait scores (MDS-UPRDS 2.11-2.13 + 3.9 3.13), turning time (seconds), stride length (meters) and velocity (meters/second) were measured 1 h after DBS changes. Motor and gait scores significantly improved with bilateral versus unilateral STN-DBS. Stride length and velocity (0.95 +/- 0.06, 0.84 +/- 0.07) significantly improved with bilateral (1.09 +/- 0.04, 0.95 +/- 0.05), right-sided (1.06 +/- 0.04, 0.92 +/- 0.05) and left-sided stimulation (1.01 +/- 0.05, 0.90 +/- 0.05) (p < 0.05). Stride length significantly improved with right-sided versus left-sided (0.05 +/- 0.02) and bilateral versus left-sided stimulation (0.07 +/- 0.02) (p < 0.05). Turning time (4.89 +/- 0.6) tended to improve with bilateral (4.13 +/- 0.5) (p = 0.15) and right-sided (4.27 +/- 0.6) (p = 0.2) more than with left STN-DBS (4.69 +/- 0.5) (p = 0.5). Bilateral STN-DBS yields greater improvement in motor and gait scores in PD patients. Yet, unilateral stimulation has similar effects on gait kinematics. Particularly, right-sided stimulation might produce slightly greater improvements. Although the clinical relevance of differential programming of right versus left-sided STN-DBS is unclear, this approach could be considered in the management of treatment-resistant gait dysfunction in PD. PMID- 27278063 TI - Effect of botulinum toxin treatment on quality of life in patients with isolated lingual dystonia and oromandibular dystonia affecting the tongue. AB - The purpose of this study was to investigate the impact of botulinum toxin (BoNT) treatment on the quality of life (QoL) for patients with prominent lingual dystonia (LD) using a disease-specific questionnaire, the oromandibular dystonia questionnaire-25 (OMDQ-25). This is a prospective, observational study of a cohort of 30 patients treated with BoNT injections for LD, with or without concurrent jaw dystonia. Primary efficacy outcome was the absolute difference between total OMDQ-25 baseline score and total OMDQ-25 scores 4 and 8 weeks after the treatment. Safety outcome was the occurrence of adverse effects. The mean total OMDQ-25 baseline score was 46.8 +/- 17.8. After BoNT treatment, there was a significant reduction in the mean total OMDQ-25 score at 4 weeks (38.2 +/- 17.6; p = 0.004), as well as at 8 weeks (39.6 +/- 18.1; p = 0.008). At the multiple regression analysis, a jaw deviation pattern (JDD) and high questionnaire baseline total score were detected as predictors of a better outcome, whilst associated jaw tremor was a predictor of poor outcome. In patients with JDD, jaw opening muscles were more frequently injected and genioglossus less frequently than in patients without JDD. No major adverse events were detected. A consistent and measurable improvement in QoL, with good safety and tolerability, can be achieved in patients with prominent LD by injecting BoNT into genioglossus and/or other muscles of the oromandibular region. PMID- 27278064 TI - Serial electrophysiological findings in Guillain-Barre syndrome not fulfilling AIDP or AMAN criteria. AB - Guillain-Barre syndrome (GBS) is categorized into two major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). However, a proportion of patients are electrophysiologically unclassified because of electrophysiological findings that do not fulfil AIDP or AMAN criteria, and underlying pathophysiological mechanisms and lesion distributions of unclassified patients are not well defined. The aims of this study are to elucidate disease pathophysiology and lesion distribution in unclassified patients. We retrospectively studied 48 consecutive GBS patients. Patients were classified on the basis of initial electrophysiological findings according to Ho's criteria. Clinical and serial electrophysiological examinations of unclassified patients were conducted. Twelve (25 %) GBS patients were unclassified. All unclassified patients were able to walk independently at 21 days after onset. No unclassified patients, except one patient with diabetes mellitus, had sensory nerve involvement. Eight patients underwent a follow-up study within 15 days of the initial study. Distal motor latencies (DMLs) of the left median motor nerve were found to be significantly and uniformly decreased compared with initial studies (p = 0.008). DMLs (p < 0.0001) and distal compound action potential (CMAP) durations (p = 0.002) of all nerves were significantly decreased, and distal CMAP amplitudes (p = 0.026) significantly increased compared with initial studies. In unclassified GBS patients, DML values during initial electrophysiological studies would be prolonged compared with expected values in the same patient unaffected by GBS and later improve rapidly with increased distal CMAP amplitudes without the development of excessive temporal dispersions. Lesions are also present in distal nerve segments caused by reversible conduction failure. PMID- 27278065 TI - Magnitude of anthropogenic phosphorus storage in the agricultural production and the waste management systems at the regional and country scales. AB - Based on a systematic review of 17 recent substance flow analyses of phosphorus (P) at the regional and country scales, this study presents an assessment of the magnitude of anthropogenic P storage in the agricultural production and the waste management systems to identify the potential for minimizing unnecessary P storage to reduce the input of P as mineral fertilizer and the loss of P. The assessment indicates that in case of all (6) P flow analyses at the regional scale, the combined mass of annual P storage in the agricultural production and the waste management systems is greater than 50 % of the mass of annual P inflow as mineral fertilizer in the agricultural production system, while this is close to or more than 100 % in case of half of these analyses. At the country scale, in case of the majority (7 out of 11) of analyses, the combined mass of annual P storage in the agricultural production and the waste management systems has been found to be roughly equivalent or greater than 100 % of the mass of annual P inflow as mineral fertilizer in the agricultural production system, while it ranged from 30 to 60 % in the remaining analyses. A simple scenario analysis has revealed that the annual storage of P in this manner over 100 years could result in the accumulation of a massive amount of P in the agricultural production and the waste management systems at both the regional and country scales. This study suggests that sustainable P management initiatives at the regional and country scales should put more emphasis on minimizing unwanted P storage in the agricultural production and the waste management systems. PMID- 27278066 TI - Industrial-scale application of the plunger flow electro-oxidation reactor in wastewater depth treatment. AB - Effluents after biochemical treatment contain pollutants that are mostly non degradable. Based upon previous pilot-scale test results, an industrial-scale electro-oxidation device was built to decompose these refractory materials in the effluent from a park wastewater treatment plant. The electro-oxidation device comprised a ditch-shaped plunger flow electrolysis cell, with mesh-plate Ti/PbO2 electrodes as the anode and the same size mesh-plate Ti as the cathode. Wastewater flowed vertically through electrodes; the effective volume of the cell was 2.8 m(3), and the surface-to-volume ratio was 17.14 m(2) m(-3). The optimal current density was 100 A m(-2), and a suitable flow velocity was 14.0 m h(-1). The removal efficiencies for chemical oxygen demand and color in the effluent were over 60.0 and 84.0 %, respectively. In addition, the electro-oxidation system offered a good disinfection capability. The specific energy consumption for this industrial-scale device was 43.5 kWh kg COD(-1), with a current efficiency of 32.8 %, which was superior to the pilot-scale one. To meet the requirements for emission or reuse, the operation cost was $0.44 per ton of effluent at an average price for electricity of $0.11 kWh(-1). PMID- 27278067 TI - Effects and mechanism of acid rain on plant chloroplast ATP synthase. AB - Acid rain can directly or indirectly affect plant physiological functions, especially photosynthesis. The enzyme ATP synthase is the key in photosynthetic energy conversion, and thus, it affects plant photosynthesis. To clarify the mechanism by which acid rain affects photosynthesis, we studied the effects of acid rain on plant growth, photosynthesis, chloroplast ATP synthase activity and gene expression, chloroplast ultrastructure, intracellular H(+) level, and water content of rice seedlings. Acid rain at pH 4.5 remained the chloroplast structure unchanged but increased the expression of six chloroplast ATP synthase subunits, promoted chloroplast ATP synthase activity, and increased photosynthesis and plant growth. Acid rain at pH 4.0 or less decreased leaf water content, destroyed chloroplast structure, inhibited the expression of six chloroplast ATP synthase subunits, decreased chloroplast ATP synthase activity, and reduced photosynthesis and plant growth. In conclusion, acid rain affected the chloroplast ultrastructure, chloroplast ATPase transcription and activity, and P n by changing the acidity in the cells, and thus influencing the plant growth and development. Finally, the effects of simulated acid rain on the test indices were found to be dose-dependent. PMID- 27278068 TI - Novel bacterial consortia isolated from plastic garbage processing areas demonstrated enhanced degradation for low density polyethylene. AB - This study aimed to formulate novel microbial consortia isolated from plastic garbage processing areas and thereby devise an eco-friendly approach for enhanced degradation of low-density polyethylene (LDPE). The LDPE degrading bacteria were screened and microbiologically characterized. The best isolates were formulated as bacterial consortia, and degradation efficiency was compared with the consortia formulated using known isolates obtained from the Microbial Culture Collection Centre (MTCC). The degradation products were analyzed by FTIR, GC-FID, tensile strength, and SEM. The bacterial consortia were characterized by 16S ribosomal DNA (rDNA) sequencing. The formulated bacterial consortia demonstrated 81 +/- 4 and 38 +/- 3 % of weight reduction for LDPE strips and LDPE pellets, respectively, over a period of 120 days. However, the consortia formulated by MTCC strains demonstrated 49 +/- 4 and 20 +/- 2 % of weight reduction for LDPE strips and pellets, respectively, for the same period. Furthermore, the three isolates in its individual application exhibited 70 +/- 4, 68 +/- 4, and 64 +/- 4 % weight reduction for LDPE strips and 21 +/- 2, 28 +/- 2, 24 +/- 2 % weight reduction for LDPE pellets over a period of 120 days (p < 0.05). The end product analysis showed structural changes and formation of bacterial film on degraded LDPE strips. The 16S rDNA characterization of bacterial consortia revealed that these organisms were novel strains and designated as Enterobacter sp. bengaluru btdsce01, Enterobacter sp. bengaluru-btdsce02, and Pantoea sp. bengaluru btdsce03. The current study thus suggests that industrial scale-up of these microbial consortia probably provides better insights for waste management of LDPE and similar types of plastic garbage. PMID- 27278069 TI - Influence of sub-lethal crude oil concentration on growth, water relations and photosynthetic capacity of maize (Zea mays L.) plants. AB - Maize tolerance potential to oil pollution was assessed by growing Zea mays in soil contaminated with varying levels of crude oil (0, 2.5 and 5.0 % v/w basis). Crude oil contamination reduced soil microflora which may be beneficial to plant growth. It was observed that oil pollution caused a remarkable decrease in biomass, leaf water potential, turgor potential, photosynthetic pigments, quantum yield of photosystem II (PSII) (Fv/Fm), net CO2 assimilation rate, leaf nitrogen and total free amino acids. Gas exchange characteristics suggested that reduction in photosynthetic rate was mainly due to metabolic limitations. Fast chlorophyll a kinetic analysis suggested that crude oil damaged PSII donor and acceptor sides and downregulated electron transport as well as PSI end electron acceptors thereby resulting in lower PSII efficiency in converting harvested light energy into biochemical energy. However, maize plants tried to acclimate to moderate level of oil pollution by increasing root diameter and root length relative to its shoot biomass, to uptake more water and mineral nutrients. PMID- 27278072 TI - New challenges for the Journal of Echocardiography with an innovative system for online submission, editorial processing, and publication. PMID- 27278070 TI - Elemental composition of Marrubium astracanicum Jacq. growing in tungsten contaminated sites. AB - This study evaluates the elemental (W, Mo, Zn, Fe, Cu, Cd, Mn, Pb, Cr, Co, B, and Bi) composition of Marrubium astracanicum Jacq. (Lamiaceae), around the abandoned tungsten mine on Uludag Mountain, Turkey, to determine if it is an appropriate candidate for phytomonitoring and/or phytoremediation purposes. Three sample sites were selected around the mine for soil and plant sampling. Two sites approximately 500 m from the mine were assumed to be unpolluted sites. The other site was selected from a waste removal pool (WRP) and was assumed to be a polluted site. The soil and different organs (roots, leaves, and flowers) of plant samples were analyzed by inductively coupled plasma-mass spectrometry (ICP MS) to determine the elemental content. The classic open wet digestion procedure was applied to the samples with 5 mL HNO3 and 3 mL H2O2 in a borosilicate glass vessel for the roots, leaves, and the flowers of the plants. Kjeldahl digestion was used for the soil samples. The W, Zn, Fe, Cu, Cd, Mn, Pb, B, and Bi contents were found to be higher in the soil samples from the waste removal pools compared with the samples from the unpolluted sites. We also found that the elemental composition of M. astracanicum has generally been increased by the activity of the tungsten mine, and there were significant correlations between the elemental contents of the soil samples and plant parts, except for Mo and Cr. The high level of many elements in the soil samples indicates the presence of contamination related to tungsten-mining activity on Uludag Mountain. Assessing the elemental contents of M. astracanicum, we can suggest this species as a candidate for phytoremediation purposes of W-contaminated sites due to its high W accumulation capacity. PMID- 27278071 TI - Acute toxicity and chemical evaluation of coking wastewater under biological and advanced physicochemical treatment processes. AB - This study investigated the changes of toxic compounds in coking wastewater with biological treatment (anaerobic reactor, anoxic reactor and aerobic-membrane bioreactor, A1/A2/O-MBR) and advanced physicochemical treatment (Fenton oxidation and activated carbon adsorption) stages. As the biological treatment stages preceding, the inhibition effect of coking wastewater on the luminescence of Vibrio qinghaiensis sp. Nov. Q67 decreased. Toxic units (TU) of coking wastewater were removed by A1/A2/O-MBR treatment process, however approximately 30 % TU remained in the biologically treated effluent. There is a tendency that fewer and fewer residual organic compounds could exert equal acute toxicity during the biological treatment stages. Activated carbon adsorption further removed toxic pollutants of biologically treated effluent but the Fenton effluent increased acute toxicity. The composition of coking wastewater during the treatment was evaluated using the three-dimensional fluorescence spectra, gas chromatography mass spectrometry (GC-MS). The organic compounds with high polarity were the main cause of acute toxicity in the coking wastewater. Aromatic protein-like matters in the coking wastewater with low biodegradability and high toxicity contributed mostly to the remaining acute toxicity of the biologically treated effluents. Chlorine generated from the oxidation process was responsible for the acute toxicity increase after Fenton oxidation. Therefore, the incorporation of appropriate advanced physicochemical treatment process, e.g., activated carbon adsorption, should be implemented following biological treatment processes to meet the stricter discharge standards and be safer to the environment. PMID- 27278073 TI - Comparison of usefulness of the wall thickness of the left anterior descending coronary artery, determined by transthoracic echocardiography, and carotid intima media thickness in predicting multivessel coronary artery disease. AB - BACKGROUND: Wall thickness in the distal part of the left anterior descending coronary artery (LAD) can be measured by using two-dimensional high-resolution transthoracic echocardiography (2DHTTE). The objective of this study was to compare the diagnostic accuracy of measuring carotid intima-media thickness (IMT) and distal LAD wall thickness for prediction of multivessel coronary artery disease (MVD). METHODS: We measured wall thickness in the distal LAD using 2DHTTE and carotid IMT using B-mode ultrasound in 100 patients who subsequently underwent coronary angiography (CAG). Patients were classified into three groups based on the results of CAG-no significant stenosis (group N), single-vessel disease (group S), or multivessel disease (group M). RESULTS: Successful measurements of LAD wall thickness were accomplished in 96 patients. Distal LAD wall thickness was significantly greater in group M (0.92 +/- 0.20 mm) than in group N (0.72 +/- 0.11 mm, P < 0.01) and group S (0.76 +/- 0.19 mm, P < 0.01). Carotid IMT was significantly greater in group M (0.90 +/- 0.24 mm) than in group N (0.75 +/- 0.21 mm, P < 0.05) and group S (0.80 +/- 0.17 mm, P < 0.05). Distal LAD wall thickness >0.8 mm had a sensitivity of 75% and a specificity of 67% in predicting MVD, whereas carotid IMT >0.8 mm was 63% sensitive and 67% specific in the prediction of MVD. There was a weak but significant correlation between distal LAD wall thickness and IMT (r = 0.31, P < 0.01). CONCLUSIONS: Non-invasive measurement of distal LAD wall thickness by 2DHTTE is feasible, and has equivalent diagnostic accuracy to IMT measurements for predicting MVD. PMID- 27278074 TI - Accuracy of three-dimensional echocardiography in patients with prior anteroseptal myocardial infarction. AB - BACKGROUND: Echocardiography is the most feasible modality for monitoring cardiac volume and function. However, conventional two-dimensional echocardiography (2DE) is frequently not accurate in measuring cardiac performance in cases of abnormal left ventricular wall motion, because of the geometric assumptions. Quantitative gated scintigraphy and magnetic resonance imaging are reliable modalities, but are expensive and not feasible for repetitive use. Real-time three-dimensional echocardiography (RT3DE) has been proved to be applicable in daily practice. The purpose of this study was to confirm the superiority of RT3DE to 2DE in assessing cardiac volume and function in patients with abnormal wall motion. METHODS: The subjects were 41 patients with old anteroseptal myocardial infarction who underwent left ventricular volume and functional measurement by RT3DE, 2DE, and left ventriculography (LVG). End-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) from RT3DE and 2DE were measured and compared with results from LVG. RESULTS: RT3DE correlated well with LVG in measurements of EDV, ESV, and EF (r = 0.815, 0.940, and 0.812, respectively; P < 0.001 each). Likewise, 2DE correlated with LVG, but underestimated left ventricular volume, particularly EDV (r = 0.652, 0.909, and 0.761, respectively; P < 0.001 each). CONCLUSION: Values derived from RT3DE were closer to those from LVG than were values derived from 2DE. RT3DE provides important information on cardiac function in patients with prior anteroseptal myocardial infarction. PMID- 27278075 TI - Transient late-onset ischemic mitral regurgitation following Dor's procedure. AB - A 60-year-old man developed anteroseptal acute myocardial infarction with subsequent left hemiplegia. Echocardiography detected apical aneurysm with thrombus. Coronary artery bypass grafting with Dor's procedure were performed. Chronic heart failure (CHF) developed three months after the surgery. CHF with mitral regurgitation (MR) continued for more than two months and then disappeared. When surgical intervention is considered for late MR after Dor's procedure, it is important to consider that late-onset MR after Dor's procedure can be transient with full medication, which may require four or more months to achieve its full effects. PMID- 27278076 TI - The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Uses its C Terminus to Regulate the A2B Adenosine Receptor. AB - CFTR is an apical membrane anion channel that regulates fluid homeostasis in many organs including the airways, colon, pancreas and sweat glands. In cystic fibrosis, CFTR dysfunction causes significant morbidity/mortality. Whilst CFTR's function as an ion channel has been well described, its ability to regulate other proteins is less understood. We have previously shown that plasma membrane CFTR increases the surface density of the adenosine 2B receptor (A2BR), but not of the beta2 adrenergic receptor (beta2AR), leading to an enhanced, adenosine-induced cAMP response in the presence of CFTR. In this study, we have found that the C terminal PDZ-domain of both A2BR and CFTR were crucial for this interaction, and that replacing the C-terminus of A2BR with that of beta2AR removed this CFTR dependency. This observation extended to intact epithelia and disruption of the actin cytoskeleton prevented A2BR-induced but not beta2AR-induced airway surface liquid (ASL) secretion. We also found that CFTR expression altered the organization of the actin cytoskeleton and PDZ-binding proteins in both HEK293T cells and in well-differentiated human bronchial epithelia. Furthermore, removal of CFTR's PDZ binding motif (DeltaTRL) prevented actin rearrangement, suggesting that CFTR insertion in the plasma membrane results in local reorganization of actin, PDZ binding proteins and certain GPCRs. PMID- 27278077 TI - High extracellular pressure promotes gastric cancer cell adhesion, invasion, migration and suppresses gastric cancer cell differentiation. AB - Slightly increased pressure stimulates tumor cell adhesion and proliferation. In the present study, we aimed to evaluate the effects of high pressure on gene expression and the biological behavior of gastric cancer cells. After incubation for 30 min at 37C under ambient and increased pressure, one portion of SGC7901 cells was used for cell proliferation and apoptosis assays, cell cycle analysis, adhesion invasion or migration assays. The other portion of cells was harvested for detection of matrix metalloproteinase-2 (MMP-2), inhibitor of DNA binding-1 (ID1), sonic Hedgehog (SHH) and E-cadherin expression by western blotting or RT PCR. In addition, we investigated the effects of high pressure on SGC7901 cell ultrastructure by transmission electron microscopy. We found that the adhesion fold under increased pressure of 760 and 1,520 mmHg was 2.39+/-1.05 (P<0.05) and 2.47+/-0.85 (P<0.01) as compared with the control, respectively. The invasion fold was 3.42+/-2.06 (P<0.05) and 5.13+/-2.49 (P<0.01) as compared with the control, respectively. The migration was 1.65+/-0.20 (P<0.001) and 2.53+/-0.50 (P<0.001) as compared with the control, respectively. At increased pressure, MMP 2 and ID1 expression increased significantly, while the expression of SHH decreased significantly. However, we did not find significant change in proliferation, apoptosis, cell cycle or ultrastructure of the SGC7901 cells under high pressure. In conclusion, high pressure promoted the adhesion, invasion and migration of SGC7901 cells. Moreover, the present study suggests that the pressure-augmented invasion and migration may be related to the increase in MMP-2 expression. Moreover, high pressure may suppress SGC7901 cell differentiation, which may result from the change in SHH and ID1 expression. PMID- 27278078 TI - Urine sampling techniques in symptomatic primary-care patients: a diagnostic accuracy review. AB - BACKGROUND: Choice of urine sampling technique in urinary tract infection may impact diagnostic accuracy and thus lead to possible over- or undertreatment. Currently no evidencebased consensus exists regarding correct sampling technique of urine from women with symptoms of urinary tract infection in primary care. The aim of this study was to determine the accuracy of urine culture from different sampling-techniques in symptomatic non-pregnant women in primary care. METHODS: A systematic review was conducted by searching Medline and Embase for clinical studies conducted in primary care using a randomized or paired design to compare the result of urine culture obtained with two or more collection techniques in adult, female, non-pregnant patients with symptoms of urinary tract infection. We evaluated quality of the studies and compared accuracy based on dichotomized outcomes. RESULTS: We included seven studies investigating urine sampling technique in 1062 symptomatic patients in primary care. Mid-stream-clean-catch had a positive predictive value of 0.79 to 0.95 and a negative predictive value close to 1 compared to sterile techniques. Two randomized controlled trials found no difference in infection rate between mid-stream-clean-catch, mid-stream-urine and random samples. CONCLUSIONS: At present, no evidence suggests that sampling technique affects the accuracy of the microbiological diagnosis in non-pregnant women with symptoms of urinary tract infection in primary care. However, the evidence presented is in-direct and the difference between mid-stream-clean catch, mid-stream-urine and random samples remains to be investigated in a paired design to verify the present findings. PMID- 27278079 TI - Academic Productivity of US Cardiothoracic Surgical Centers. AB - BACKGROUND AND AIM: We investigated which metrics represent valid correlates of the academic productivity of cardiothoracic (CT) surgical centers. METHODS: We collected data from 57 US academic CT surgical groups (663 surgeons), including H index and institutional role of each surgeon, ranking by US News & World Report (USNWR) and NIH funding, and designation as department versus division. RESULTS: Academic productivity (median H-index of each group) was significantly different across institutions (p < 0.001). Several USNWR hospital categories ("Honor Roll", "Adult Cardiology and Heart Surgery", "Adult Pulmonology", "Adult Cancer") and medical school ranking for research were associated with differences in academic productivity, while ranking by NIH funding or designation as department versus division was not. Groups with chairperson's individual H-index >=50 were overall more productive than those with chairperson's H-index <50 (median H-index: 18 vs. 14; p = 0.005). CONCLUSIONS: USNWR rankings provide a good representation of academic productivity, while NIH funding ranking or designation as department versus division does not. The individual productivity of the chairperson is correlated with that of the whole group. doi: 10.1111/jocs.12773 (J Card Surg 2016;31:423-428). PMID- 27278080 TI - Calibrating the impact of dual RAAS blockade on the heart and the kidney - balancing risks and benefits. AB - Overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in the pathophysiology of heart failure (HF) and chronic kidney disease (CKD). RAAS antagonists can significantly improve clinical outcomes, but monotherapy blocks but one step of the RAAS and can be bypassed through compensatory mechanisms. Providing more complete RAAS blockade by deploying drugs with complementary actions seemed logical - hence the practice of using dual (or triple) RAAS inhibitors. However, RAAS antagonists also exhibit dose-limiting side effects, including acute kidney injury, hyperkalaemia and hypotension, which blunt their overall effectiveness. Despite achieving better RAAS blockade, several trials failed to show clinical outcome improvements. Patients with concomitant CKD and HF (cardiorenal syndrome) are at the greatest risk of these adverse events and therefore the least able to benefit, yet they also have the worst prognosis. This paradox, where those most in need have fewest therapeutic options, poses three questions which are the focus of this review: whether (i) novel therapies that prevent adverse effects can restore therapeutic benefits to patients who would otherwise be RAAS-therapy intolerant, (ii) there are any validated alternatives to their use and (iii) newer approaches to the detection of fluid congestion are ready for implementation. PMID- 27278082 TI - Neutral detergent fiber increases endogenous ileal losses but has no effect on ileal digestibility of amino acids in growing pigs. AB - Two experiments were conducted to determine the effect of neutral detergent fiber (NDF) on endogenous amino acids and protein ileal losses; and also apparent ileal digestibility (AID), and standardized ileal digestibility (SID) of amino acids and crude protein. Sixteen barrows were fed four protein-free diets containing graded NDF levels in Experiment 1. NDF was a mixture of sugarcane bagasse and corn leaves (SBCL). Twenty-four barrows were fed diets with soybean protein concentrate (SPC) or casein as protein sources and SBCL or corncobs (CC) as NDF sources in Experiment 2. In Experiment 1, a linear increase (P < 0.05) in endogenous amino acid and protein ileal losses was observed with increased NDF levels, except for arginine, histidine, methionine and proline. In Experiment 2, protein (P < 0.001) and NDF (P < 0.01) sources significantly affected AID of dry matter, which was higher in casein diets (71.7%) and CC diets (70.7%). Protein and NDF sources significantly affected (P < 0.05) SID of crude protein, which was higher in casein diets (92.8%) and CC diets (92.7%). NDF source had no effect (P > 0.05) on SID of amino acids. Overall, this study showed that NDF increased endogenous amino acid and protein ileal losses, but did not affect ileal digestibility of amino acids. PMID- 27278081 TI - Incomplete radiofrequency ablation accelerates proliferation and angiogenesis of residual lung carcinomas via HSP70/HIF-1alpha. AB - Radiofrequency ablation (RFA) therapy has been proved effective and feasible for lung cancer. However, the molecular mechanisms of local lung cancer recurrence following RFA are poorly understood. The present study aimed to evaluate the ability of HSP70/HIF-1alpha to affect the proliferation and angiogenesis of non small cell lung cancers (NSCLCs) following insufficient RFA to uncover the molecular mechanisms of local recurrence. In vitro heat treatment was used to establish sublines of NCI-H1650 cells. The NCI-H1650 subline that was established by heat treatment at 54C had a relatively higher viability and significantly elevated heat tolerance (compared to the parental strain). After treatment with the HSP70 inhibitor VER-155008, the HIF-1alpha inhibitor YC-1 and PI3K/Akt inhibitor wortmannin, the viability and proliferation rate of the cells was measured. At the same time, HSP70, HIF-1alpha and Akt were detected by real-time PCR and western blotting. In vivo xenograft tumors were created by subcutaneously inoculating nude mice with NCI-H1650 cells. HSP70, HIF-1alpha and Akt were detected by western blotting, and CD34 expression was detected by immunohistochemistry before and after RFA or treatment with the VER-155008, YC-1 or wortmannin inhibitors. The heat-adapted NCI-H1650 subline established in vitro had a higher viability and proliferative activity compared to parental cells. Inhibiting HSP70/HIF-1alpha abolished this difference. Blocking the PI3K/Akt signaling pathway decreased HSP70/HIF-1alpha expression levels. In vivo, we found that incomplete RFA treatment promoted HSP70/HIF-1alpha and CD34 expression. Additionally, the combination of RFA and treatment targeting HSP70/HIF-1alpha resulted in a synergistic reduction in tumor growth compared to incomplete RFA alone. The PI3K/Akt signaling pathway is also involved in regulating HSP70/HIF 1alpha expression during this process. We conclude that the accelerated proliferation and angiogenesis potential of residual lung carcinomas following RFA treatment was induced by HSP70/HIF-1alpha, expression of which is regulated by the PI3K/Akt signaling pathway. PMID- 27278083 TI - Agency alters perceptual decisions about action-outcomes. AB - Humans experience themselves as agents, capable of controlling their actions and the outcomes they generate (i.e., the sense of agency). Inferences of agency are not infallible. Research shows that we often attribute outcomes to our agency even though they are caused by another agent. Moreover, agents report the sensory events they generate to be less intense compared to the events that are generated externally. These effects have been assessed using highly suprathreshold stimuli and subjective measurements. Consequently, it remains unclear whether experiencing oneself as an agent lead to a decision criterion change and/or a sensitivity change. Here, we investigate this issue. Participants were told that their key presses generated an upward dot motion but that on 30 % of the trials the computer would take over and display a downward motion. The upward/downward dot motion was presented at participant's discrimination threshold. Participants were asked to indicate whether they (upward motion) or the computer (downward motion) generated the motion. This group of participants was compared with a 'no agency' group who performed the same task except that subjects did not execute any actions to generate the dot motion. We observed that the agency group reported seeing more frequently the motion they expected to generate (i.e., upward motion) than the no-agency group. This suggests that agency distorts our experience of (allegedly) caused events by altering perceptual decision processes, so that, in ambiguous contexts, externally generated events are experienced as the outcomes of one's actions. PMID- 27278085 TI - Conversation game: talking bacteria. AB - The story of autonomous unicellular organisms, bacteria with unimaginable computational and evolutionary capabilities along with collective behavior has been running since the first six decades of the twentieth Century. However, do not consider them to be small and simple, because they possess the generic term quorum sensing adopted to describe the cell communication process which co ordinate gene expression, when the population has reached a high cell density. Bacteria release diffusible signal molecules known as autoinducers or quorum sensing molecules. In recent research, the direction for activating or deactivating nature of a wave of gene expression is predicted experimentally which control bacterial populations subject to a diffusing autoinducer signal. On the other hand, it has been observed that the accumulation of the quorum sensing molecules leads to a negative diffusion coefficient in the solution of governing differential equation. PMID- 27278084 TI - Nerve crush but not displacement-induced stretch of the intra-arachnoidal facial nerve promotes facial palsy after cerebellopontine angle surgery. AB - Little is known about the reasons for occurrence of facial nerve palsy after removal of cerebellopontine angle tumors. Since the intra-arachnoidal portion of the facial nerve is considered to be so vulnerable that even the slightest tension or pinch may result in ruptured axons, we tested whether a graded stretch or controlled crush would affect the postoperative motor performance of the facial (vibrissal) muscle in rats. Thirty Wistar rats, divided into five groups (one with intact controls and four with facial nerve lesions), were used. Under inhalation anesthesia, the occipital squama was opened, the cerebellum gently retracted to the left, and the intra-arachnoidal segment of the right facial nerve exposed. A mechanical displacement of the brainstem with 1 or 3 mm toward the midline or an electromagnet-controlled crush of the facial nerve with a tweezers at a closure velocity of 50 and 100 mm/s was applied. On the next day, whisking motor performance was determined by video-based motion analysis. Even the larger (with 3 mm) mechanical displacement of the brainstem had no harmful effect: The amplitude of the vibrissal whisks was in the normal range of 50 degrees -60 degrees . On the other hand, even the light nerve crush (50 mm/s) injured the facial nerve and resulted in paralyzed vibrissal muscles (amplitude of 10 degrees -15 degrees ). We conclude that, contrary to the generally acknowledged assumptions, it is the nerve crush but not the displacement-induced stretching of the intra-arachnoidal facial trunk that promotes facial palsy after cerebellopontine angle surgery in rats. PMID- 27278086 TI - S100A4 influences cancer stem cell-like properties of MGC803 gastric cancer cells by regulating GDF15 expression. AB - Many studies have revealed that S100A4 is involved in cancer progression by affecting a variety of biological functions. Our previous study showed that S100A4 influences many biological properties of gastric cancer cells; however, the underlying mechanisms are far from clear. In this study, we used cDNA microarray analysis to investigate the global alterations in gene expression in MGC803 gastric cancer cells after siRNA-mediated S100A4 inhibition. Among the total genes investigated, 179 differentially expressed genes (38 upregulated and 141 downregulated) were detected in S100A4-siRNA transfected MGC803 cells compared with NC-siRNA transfected cells. We focused on the GDF15 gene, which was significantly downregulated after S100A4 inhibition. ChIP studies showed that the S100A4 protein binds to the GDF15 promoter, implicating S100A4 in GDF15 regulation at the transcriptional level. GDF15 overexpression promoted CSC-like properties of MGC803 cells, such as spheroid and soft-agar colony forming abilities. S100A4 inhibition suppressed the CSC-like properties of the cells, whereas, GV141-GDF15 vector transfection reversed these effects. Our results suggest that S100A4 influences the CSC-like properties of MGC803 gastric cancer cells by regulating GDF15 expression. PMID- 27278087 TI - Aspects of fish conservation in the upper Patos Lagoon basin. AB - The Patos Lagoon basin is a large (201 626 km(2) ) and complex drainage system in southern Brazil. The lagoon is 250 km long and 60 km wide, covering an area of 10 360 km(2) . The exchange of water with the Atlantic Ocean occurs through a 0.8 km wide and 15 m deep inlet, fixed by 4 km long jetties, at the southernmost part of the Patos Lagoon. The estuarine area is restricted to its southern portion (10%), although the upper limit of saline waters migrates seasonally and year to year, influenced by the wind regime and river discharge. The known number of recorded limnetic fish species is 200, but this number is expected to increase. A higher endemism is observed in fish species occurring in upper tributaries. The basin suffers from the direct impact of almost 7 million inhabitants, concentrated in small to large cities, most with untreated domestic effluents. There are at least 16 non-native species recorded in natural habitats of the Patos Lagoon basin, about half of these being from other South American river basins. Concerning the fishery, although sport and commercial fisheries are widespread throughout the Patos Lagoon basin, the lagoon itself and the estuarine area are the main fishing areas. Landing statistics are not available on a regular basis or for the whole basin. The fishery in the northern Patos Lagoon captures 31 different species, nine of which are responsible for most of the commercial catches, but only three species are actually sustaining the artisanal fishery: the viola Loricariichthys anus: 455 kg per 10 000 m(2) gillnet per day, the mullet Mugil liza: 123 kg per 10 000 m(2) gillnet per day and the marine catfish Genidens barbus: 50 kg per 10 000 m(2) gillnet per day. A decline of the fish stocks can be attributed to inadequate fishery surveillance, which leads to overfishing and mortality of juveniles, or to decreasing water quality because of urban and industrial activities and power production. Global climatic changes also represent a major threat to the Patos system by changing the frequency of El Nino-La Nina-Southern Oscillation (ENSO). PMID- 27278088 TI - Ultrasound assessment of perinatal testicular torsion. AB - OBJECTIVE: The goal of this study was to elucidate the different sonographic features of prenatal and postnatal testicular torsion (TT) using high-frequency colour Doppler ultrasound (HCDU) in an effort to increase diagnostic accuracy. METHODS: 29 patients (average age, 7.5 days) with perinatal TT were divided into patients with postnatal (acute) TT vs patients with prenatal (chronic) TT and their clinical characteristics, imaging features on HCDU and surgical pathology results were retrospectively analyzed. RESULTS: Significant differences were observed between prenatal and postnatal TT cases with regard to testicular size (p = 0.01) and echogenicity (p = 0.007). All 17 prenatal cases had non homogeneous testicular parenchymal echo patterns compared with only 9 (64.3%) postnatal TT cases. Five postnatal TT cases presented with homogeneous echo patterns compared with none of the prenatal TT cases. Testicular blood supply was absent in 25 (80.7%) of 31 testes on colour Doppler flow imaging, with the majority occurring in the prenatal TT cases [i.e. 16 (94.1%) cases]. 1 affected testis out of a total 17 testes from 16 patients with prenatal TT was salvaged, with a salvage rate of 1/17 or 0.06%. 7 affected testes out of a total 16 testes from 13 patients with postnatal neonatal TT were salvaged, with a salvage rate of 7/16 or 43.8%. CONCLUSION: In neonates with acute scrotal symptoms, the possibility of perinatal TT should be considered and HCDU examination should be performed in a timely manner. HCDU examination could aid in testicular salvage by prompting quick surgical intervention. ADVANCES IN KNOWLEDGE: This study underlined the clinical contribution of HCDU in evaluating postnatal (acute) vs prenatal (chronic) TT. The sonographic features of postnatal TT with salvageable testes were compared with prenatal torsion and the relative salvage rates in both cases were discussed. PMID- 27278089 TI - Tris(pentafluorophenyl)borane as an efficient catalyst in the guanylation reaction of amines. AB - Tris(pentafluorophenyl)borane, [B(C6F5)3], has been used as an efficient catalyst in the guanylation reaction of amines with carbodiimide under mild conditions. A combined approach involving NMR spectroscopy and DFT calculations was employed to gain a better insight into the mechanistic features of this process. The results allowed us to propose a new Lewis acid-assisted Bronsted acidic pathway for the guanylation reaction. The process starts with the interaction of tris(pentafluorphenyl)borane and the amine to form the corresponding adduct, [(C6F5)3B-NRH2] , followed by a straightforward proton transfer to one of the nitrogen atoms of the carbodiimide, (i)PrN[double bond, length as m-dash]C[double bond, length as m-dash]N(i)Pr, to produce, in two consequent steps, a guanidine borane adduct, [(C6F5)3B-NRC(N(i)PrH)2] . The rupture of this adduct liberates the guanidine product RNC(N(i)PrH)2 and interaction with additional amine restarts the catalytic cycle. DFT studies have been carried out in order to study the thermodynamic characteristics of the proposed pathway. Significant borane adducts with amines and guanidines have been isolated and characterized by multinuclear NMR in order to study the N-B interaction and to propose the existence of possible Frustrated Lewis Pairs. Additionally, the molecular structures of significant components of the catalytic cycle, namely 4-tert butylaniline-[B(C6F5)3] adduct and both free and [B(C6F5)3]-bonded 1-(phenyl)-2,3 diisopropylguanidine, and respectively, have been established by X-ray diffraction. PMID- 27278090 TI - Vertical transport and plant uptake of nanoparticles in a soil mesocosm experiment. AB - BACKGROUND: Agricultural soils represent a potential sink for increasing amounts of different nanomaterials that nowadays inevitably enter the environment. Knowledge on the relation between their actual exposure concentrations and biological effects on crops and symbiotic organisms is therefore of high importance. In this part of a joint companion study, we describe the vertical translocation as well as plant uptake of three different titanium dioxide (nano )particles (TiO2 NPs) and multi-walled carbon nanotubes (MWCNTs) within a pot experiment with homogenously spiked natural agricultural soil and two plant species (red clover and wheat). RESULTS: TiO2 NPs exhibited limited mobility from soil to leachates and did not induce significant titanium uptake into both plant species, although average concentrations were doubled from 4 to 8 mg/kg Ti at the highest exposures. While the mobility of MWCNTs in soil was limited as well, microwave-induced heating suggested MWCNT-plant uptake independent of the exposure concentration. CONCLUSIONS: Quantification of actual exposure concentrations with a series of analytical methods confirmed nominal ones in soil mesocosms with red clover and wheat and pointed to low mobility and limited plant uptake of titanium dioxide nanoparticles and carbon nanotubes. PMID- 27278091 TI - Clonal expansion of antitumor T cells in breast cancer correlates with response to neoadjuvant chemotherapy. AB - The immune microenvironment of tumor plays a critical role in therapeutic responses to chemotherapy. Cancer tissues are composed of a complex network between antitumor and pro-tumor immune cells and molecules; therefore a comprehensive analysis of the tumor immune condition is imperative for better understanding of the roles of the immune microenvironment in anticancer treatment response. In this study, we performed T cell receptor (TCR) repertoire analysis of tumor infiltrating T cells (TILs) in cancer tissues of pre- and post neoadjuvant chemotherapy (NAC) from 19 breast cancer patients; five cases showed CR (complete response), ten showed PR (partial response), and four showed SD/PD (stable disease/progressive disease) to the treatment. From the TCR sequencing results, we calculated the diversity index of the TCRbeta chain and found that clonal expansion of TILs could be detected in patients who showed CR or PR to NAC. Noteworthy, the diversity of TCR was further reduced in the post-NAC tumors of CR patients. Our quantitative RT-PCR also showed that expression ratio of CD8/Foxp3 was significantly elevated in the post-NAC tumors of CR cases (p=0.0032), indicating that antitumor T cells were activated and enriched in these tumors. Collectively, our findings suggest that the clonal expansion of antitumor T cells may be a critical factor associated with response to chemotherapy and that their TCR sequences might be applicable for the development of TCR-engineered T cells treatment for individual breast cancer patients when their tumors relapse. PMID- 27278093 TI - Efficacy of concurrent treatments in idiopathic pulmonary fibrosis patients with a rapid progression of respiratory failure: an analysis of a national administrative database in Japan. AB - BACKGROUND: Some IPF patients show a rapid progression of respiratory failure. Most patients are treated with high-dose corticosteroids. However, no large clinical studies have investigated the prognosis or efficacy of combined treatments including high-dose corticosteroids in IPF patients with a rapid progression of respiratory failure. METHODS: We enrolled IPF patients who received mechanical ventilation and high-dose corticosteroids between April 2010 and March 2013. Records were extracted from a Japanese nationwide inpatient database. We conducted a retrospective epidemiologic and prognostic analysis. RESULTS: Two hundred nine patients receiving an average of 12.8 days of ventilatory support were enrolled. There were 138 (66 %) fatal cases; the median survival was 21 days. The short-term (within 30 days) and long-term (within 90 days) survival rates were 44.6 and 24.6 %, respectively. The average monthly admission rate among the IPF patients with the rapid progression of respiratory failure in the winter was significantly higher than that in spring (p = 0.018). Survival did not differ to a statistically significant extent in the different geographic areas of Japan. Survivors were significantly younger (p = 0.002) with higher rates of mild dyspnea on admission (p = 0.012), they more frequently underwent bronchoscopy (p < 0.001), and received anticoagulants (p = 0.027), co trimoxazole (p < 0.001) and macrolide (p = 0.02) more frequently than non survivors. A multivariate logistic analysis demonstrated that two factors were significantly associated with a poor prognosis: >80 years of age (OR = 2.94, 95 % Cl 1.044-8.303; p = 0.041) and the intravenous administration of high-dose cyclophosphamide (OR = 3.17, 95 % Cl 1.101-9.148; p = 0.033). Undergoing bronchoscopy during intubation (OR = 0.25, 95 % Cl 0.079-0.798; p = 0.019) and the administration of co-trimoxazole (OR = 0.28, 95 % Cl 0.132-0.607; p = 0.001) and macrolides (OR = 0.37, 95 % Cl 0.155-0.867; p = 0.033) were significantly associated with a good prognosis. The dosage of co-trimoxazole significantly correlated with survival. CONCLUSIONS: Co-trimoxazole and macrolides may be a good addition to high-dose corticosteroids in the treatment of IPF patients with a rapid progression of respiratory failure. PMID- 27278095 TI - Acute plasma amylase increase after glucagon-like peptide -1 receptor agonist exenatide administration in Type 2 diabetes. PMID- 27278096 TI - How to develop a more accurate risk prediction model when there are few events. PMID- 27278094 TI - Rel B-modified dendritic cells possess tolerogenic phenotype and functions on lupus splenic lymphocytes in vitro. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by high morbidity and mortality and its treatment remains challenging. Dendritic cells (DCs) have been shown to participate in the initiation and perpetuation of lupus pathogenesis and the DCs that can induce tolerogenicity appear as potential cell-based therapy in this condition. In this study, we examined the in vitro tolerogenic properties of bone-marrow derived DCs (BMDCs) in the murine lupus setting. We used lentiviral transduction of RelB-silencing short hairpin RNA to modify the expression of RelB, a key transcription factor regulating DC maturation, in BMDCs from MRL/MpJ mice. Tolerogenic properties of RelB-modified DCs were compared with scrambled control (SC) -modified DCs. RelB expression was found to be significantly reduced in RelB-modified DCs derived from MRL/MpJ mice, wild-type of the same genetic background as MRL/lpr lupus-prone mice. These MRL/MpJ RelB-modified DCs displayed semi-mature phenotype with expression of lower levels of co-stimulatory molecules compared with SC-modified DCs. RelB modified DCs were found to be low producers of interleukin-12p70 (IL-12p70) and could induce hyporesponsiveness of splenic T cells from MRL/MpJ and MRL/lpr mice. Furthermore, they down-regulated interferon-gamma expression and induced IL-10 producing T cells in MRL/MpJ splenocytes, and attenuated interferon-gamma and IL 17 expression in MRL/lpr splenic CD4(+) lymphocytes. Splenocytes primed by RelB modified DCs demonstrated antigen-specific suppressive effects on allogeneic splenocytes. In conclusion, RelB-silencing in DCs generates DCs of tolerogenic properties with immunomodulatory function and appears as potential option of cell targeted therapy. PMID- 27278098 TI - Lipoic acid stimulates bone formation in ovariectomized rats in a dose-dependent manner. AB - This study was undertaken to determine the osteotropic effect of different doses of lipoic acid (LA) on the mineralization of bone tissue in female Wistar rats with experimental osteopenia induced by bilateral ovariectomy. Fifty-six rats were randomly selected and submitted to either a sham operation (n = 8) or an ovariectomy (n = 48). The ovariectomized rats were randomly placed into two control groups, treated subcutaneously with either physiological saline or 17beta estradiol in the dose of 4 MUg/kg body mass per day, and four experimental groups that received LA subcutaneously in the doses of 12.5, 25, 50, and 100 mg/kg body mass per day (n = 8 in each group). After 28 days of experimental treatment, the rats were sacrificed, and body mass, total skeletal density, and body composition were recorded. Blood serum and isolated femora were stored for further analysis. Our results revealed that the osteoprotective effect of LA was dose-dependent and was observed in rats treated with 50 and 100 mg/kg of LA. Moreover, the LA applied to the ovariectomized rats in the dose of 50 mg/kg not only stopped the bone resorption, but stimulated its formation. PMID- 27278097 TI - Donor-Derived Exosomes With Lung Self-Antigens in Human Lung Allograft Rejection. AB - The immunological role of exosomes in allograft rejection remains unknown. We sought to determine whether exosomes are induced during lung allograft rejection and to define the antigenic compositions of HLA, lung-associated self-antigens (SAgs) and microRNAs (miRNAs). Exosomes were isolated from sera and bronchoalveolar lavage fluid from 30 lung transplant recipients (LTxRs) who were stable or who had acute rejection (AR) or bronchiolitis obliterans syndrome (BOS). Exosomes were defined by flow cytometry for CD63 and western blotting for annexin V SAgs, collagen V (Col-V) and Kalpha1 tubulin were examined by electron microscopy; miRNAs were profiled by a miRNA array. Donor HLA and SAgs were detected on exosomes from LTxRs with AR and BOS but not from stable LTxRs. Exosomes expressing Col-V were isolated from sera from LTxRs 3 mo before AR and 6 mo before BOS diagnosis, suggesting that exosomes with SAgs may be a noninvasive rejection biomarker. Exosomes isolated from LTxRs with AR or BOS also contained immunoregulatory miRNAs. We concluded that exosomes expressing donor HLA, SAgs and immunoregulatory miRNAs are present in the circulation and local site after human lung transplantation and play an important role in the immune pathogenesis of acute allograft rejection and BOS. PMID- 27278099 TI - Self-medication practices among undergraduate nursing and midwifery students in Australia: a cross-sectional study. AB - BACKGROUND: Self-medication is a global phenomenon and a major form of self-care. OBJECTIVES: To explore the self-medication practices of Australian nursing and midwifery students. METHODS: An online questionnaire that examined the prevalence of self-medication, reasons for self-medication, medications consumed and medication knowledge was distributed to student nurses and midwives at one university in Victoria, Australia. Data were collected between February and May 2014. RESULTS: Self-medication practices were reported in 91.7% (n = 110) of students. Students reported the main reason for self-medication was to play an active role in their health. The incidence of stress was high (n = 82, 74.5%), along with back pain (n = 84, 76.4%) and nearly half the students (n = 46, 42.2%) reported using antibiotics that were prescribed for a previous health problem. CONCLUSION: Self-medication practices were common in this student cohort and some results give rise to concern for the general wellbeing of our future nursing and midwifery workforce. PMID- 27278100 TI - Differential induction of type I interferons in macaques by wild-type measles virus alone or with the hemagglutinin protein of the Edmonston vaccine strain. AB - Measles vaccines are highly effective and safe; however, the mechanism(s) underlying their attenuation has not been well understood. In this study, type I IFNs (IFN-alpha and IFN-beta) induction in macaques infected with measles virus (MV) strains was examined. Type I IFNs were not induced in macaques infected with wild-type MV. However, IFN-alpha was sharply induced in most macaques infected with recombinant wild-type MV bearing the hemagglutinin (H) protein of the Edmonston vaccine strain. These results indicate that the H protein of MV vaccine strains may have a role in MV attenuation. PMID- 27278101 TI - Making the journey with me: a qualitative study of experiences of a bespoke mental health smoking cessation intervention for service users with serious mental illness. AB - BACKGROUND: Smoking is one of the major modifiable risk factors contributing to early mortality for people with serious mental illness. However, only a minority of service users access smoking cessation interventions and there are concerns about the appropriateness of generic stop-smoking services for this group. The SCIMITAR (Smoking Cessation Intervention for Severe Mental Ill-Health Trial) feasibility study explored the effectiveness of a bespoke smoking cessation intervention delivered by mental health workers. This paper reports on the nested qualitative study within the trial. METHODS: Qualitative semi-structured interviews were conducted with 13 service users receiving the intervention and 3 of the MHSCPs (mental health smoking cessation practitioners) delivering the intervention. Topic guides explored the perceived acceptability of the intervention particularly in contrast to generic stop-smoking services, and perceptions of the implementation of the intervention in practice. Transcripts were analysed using the Constant Comparative Method. RESULTS: Generic services were reported to be inappropriate for this group, due to concerns over stigma and a lack of support from health professionals. The bespoke intervention was perceived positively, with both practitioners and service users emphasising the benefits of flexibility and personalisation in delivery. The mental health background of the practitioners was considered valuable not only due to their increased understanding of the service users' illness but also due to the more collaborative relationship style they employed. Challenges involved delays in liaising with general practitioners and patient struggles with organisation and motivation, however the MHSCP was considered to be well placed to address these problems. CONCLUSION: The bespoke smoking cessation intervention was acceptable to service users and the both service users and practitioners reported the value of a protected mental health worker role for delivering smoking cessation to this group. The results have wider implications for understanding how to achieve integrated and personalised care for this high-risk population and further underscore the need for sensitised smoking cessation support for people with serious mental illness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN79497236 . Registered 3(rd) July 2009. PMID- 27278103 TI - Erratum to: Is the use of thin, highly cross-linked polyethylene liners safe in total hip arthroplasty? PMID- 27278102 TI - Dynamic protein coronas revealed as a modulator of silver nanoparticle sulphidation in vitro. AB - Proteins adsorbing at nanoparticles have been proposed as critical toxicity mediators and are included in ongoing efforts to develop predictive tools for safety assessment. Strongly attached proteins can be isolated, identified and correlated to changes in nanoparticle state, cellular association or toxicity. Weakly attached, rapidly exchanging proteins are also present at nanoparticles, but are difficult to isolate and have hardly been examined. Here we study rapidly exchanging proteins and show for the first time that they have a strong modulatory effect on the biotransformation of silver nanoparticles. Released silver ions, known for their role in particle toxicity, are found to be trapped as silver sulphide nanocrystals within the protein corona at silver nanoparticles in serum-containing cell culture media. The strongly attached corona acts as a site for sulphidation, while the weakly attached proteins reduce nanocrystal formation in a serum-concentration-dependent manner. Sulphidation results in decreased toxicity of Ag NPs. PMID- 27278105 TI - Deceived by orchids: sex, science, fiction and Darwin. AB - Between 1916 and 1927, botanists in several countries independently resolved three problems that had mystified earlier naturalists - including Charles Darwin: how did the many species of orchid that did not produce nectar persuade insects to pollinate them? Why did some orchid flowers seem to mimic insects? And why should a native British orchid suffer 'attacks' from a bee? Half a century after Darwin's death, these three mysteries were shown to be aspects of a phenomenon now known as pseudocopulation, whereby male insects are deceived into attempting to mate with the orchid's flowers, which mimic female insects; the males then carry the flower's pollen with them when they move on to try the next deceptive orchid. Early twentieth-century botanists were able to see what their predecessors had not because orchids (along with other plants) had undergone an imaginative re-creation: Darwin's science was appropriated by popular interpreters of science, including the novelist Grant Allen; then H.G. Wells imagined orchids as killers (inspiring a number of imitators), to produce a genre of orchid stories that reflected significant cultural shifts, not least in the presentation of female sexuality. It was only after these changes that scientists were able to see plants as equipped with agency, actively able to pursue their own, cunning reproductive strategies - and to outwit animals in the process. This paper traces the movement of a set of ideas that were created in a context that was recognizably scientific; they then became popular non-fiction, then popular fiction, and then inspired a new science, which in turn inspired a new generation of fiction writers. Long after clear barriers between elite and popular science had supposedly been established in the early twentieth century, they remained porous because a variety of imaginative writers kept destabilizing them. The fluidity of the boundaries between makers, interpreters and publics of scientific knowledge was a highly productive one; it helped biology become a vital part of public culture in the twentieth century and beyond. PMID- 27278104 TI - Salvianolic Acid B Attenuates Experimental Pulmonary Fibrosis through Inhibition of the TGF-beta Signaling Pathway. AB - Pulmonary fibrosis is a progressive and fatal disorder. In our previous study, we found that the Yiqihuoxue formula (YQHX), a prescription of Traditional Chinese Medicine, had a curative effect on scleroderma, a typical fibrotic disease. The aim of this study was to determine the key ingredient mediating the therapeutic effects of YQHX and to examine its effect on pulmonary fibrosis, including its mechanism. Luciferase reporter assays showed that the most important anti fibrotic component of the YQHX was Salviae miltiorrhiza (SM). Experiments performed using a bleomycin-instilled mouse model of pulmonary fibrosis showed that Salvianolic acid B (SAB), the major ingredient of SM, had strong anti inflammatory and anti-fibrotic effects through its inhibition of inflammatory cell infiltration, alveolar structure disruption, and collagen deposition. Furthermore, SAB suppressed TGF-beta-induced myofibroblastic differentiation of MRC-5 fibroblasts and TGF-beta-mediated epithelial-to-mesenchymal transition of A549 cells by inhibiting both Smad-dependent signaling and the Smad-independent MAPK pathway. Taken together, our results suggest that SM is the key anti fibrotic component of the YQHX and that SAB, the major ingredient of SM, alleviates experimental pulmonary fibrosis both in vivo and in vitro by inhibiting the TGF-beta signaling pathway. Together, these results suggest that SAB potently inhibits pulmonary fibrosis. PMID- 27278106 TI - Balancing benefits and harms: privacy protection policies. PMID- 27278108 TI - A Pilot Test of Self-Affirmations to Promote Smoking Cessation in a National Smoking Cessation Text Messaging Program. AB - BACKGROUND: Although effective smoking cessation treatments, including mHealth interventions, have been empirically validated and are widely available, smoking relapse is likely. Self-affirmation, a process through which individuals focus on their strengths and behaviors, has been shown to reduce negative effects of self threats and to promote engagement in healthier behavior. OBJECTIVE: To assess the feasibility of incorporating self-affirmations into an existing text messaging based smoking cessation program (Smokefree TXT) and to determine whether self affirmation led to greater engagement and higher cessation rates than the standard intervention. METHODS: Data were collected from smokers (n=1261) who subscribed to a free smoking cessation program and met eligibility criteria. The intervention lasted 42 days. The original design was a 2 (Baseline affirmation: 5 item questionnaire present vs absent) * 2 (Integrated affirmation: texts present vs absent) factorial design. Only 17 eligible users completed all baseline affirmation questions and these conditions did not influence any outcomes, so we collapsed across baseline affirmation conditions in analysis. In the integrated affirmation conditions, affirmations replaced approximately 20% of texts delivering motivational content. RESULTS: In all, 687 users remained enrolled throughout the 42-day intervention and 81 reported smoking status at day 42. Among initiators (n=1261), self-affirmation did not significantly improve (1) intervention completion, (2) days enrolled, (3) 1-week smoking status, or (4) 6 week smoking status (all Ps>.10); and among the 687 completers, there were no significant effects of affirmation on cessation (Ps>.25). However, among the 81 responders, those who received affirmations were more likely to report cessation at 6 weeks (97.5%; 39 of 40) than those not given affirmations (78.1%; 32 of 41; chi(2)(1)=7.08, P=.008). CONCLUSION: This proof-of-concept study provides preliminary evidence that self-affirmation can be integrated into existing text based cessation programs, as the affirmations did not lead to any adverse effects (ie, less engagement or lower rates of cessation). Among those who reported smoking status at the end of the intervention period (6.4% of eligible respondents), affirmations facilitated cessation. This study provides a "proof-of concept" that brief, low-touch interventions may be integrated into a text messaging program with potential benefits, minimal disruption to the program or users, and little cost. Many questions remain regarding how self-affirmation and similar approaches can promote engagement in population interventions. PMID- 27278107 TI - Comparison of equations for dosing of medications in renal impairment. AB - AIM: The aim of this study is to determine the concordance among the Cockcroft Gault, the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in hypothetical dosing of renally cleared medications. METHODS: A total of 2163 patients prescribed at least one of the 31 renally cleared drugs under review were included in the study. Kidney function was estimated using the three equations. We compared actual prescribed dosages of the same drug with recommended dosages based on the kidney function as calculated by each of the equations and applying dosing recommendations in the Australian Medicines Handbook. RESULTS: There was a significant difference in the kidney function values estimated from the three equations (P < 0.001). Despite the good overall agreement in renal drug dosing, we found selected but potentially important discrepancies among the doses rendered from the equations. The CKD-EPI equation non-normalized for body surface area had a greater rate of concordance with the Cockcroft-Gault equation than the Modification of Diet in Renal Disease equation for renal drug dosing. CONCLUSIONS: There is need for a long-term multi-centre study in a diverse population to define the clinical effects of the discrepancies among the equations for drug dosing. Given the greater concordance of the non-normalized CKD-EPI equation with the Cockcroft Gault equation for dosing, the recommendation by Kidney Health Australia and the United States National Kidney Disease Education Program that 'dosing based on either eCrCl or an eGFR with body surface area normalization removed are acceptable' seems suitable and practicable for the purpose of dosing of non critical drugs in the primary care setting. PMID- 27278109 TI - Pharmaceutical cocrystals: walking the talk. AB - Pharmaceutical cocrystals belong to a sub-class of cocrystals wherein one of the components is a drug molecule (or an active pharmaceutical ingredient, API) and the second is a benign food or drug grade additive (generally regarded as safe, GRAS). The two components are hydrogen-bonded in a fixed stoichiometric ratio in the crystal lattice. In the past decade, pharmaceutical cocrystals have demonstrated significant promise in their ability to modify the physicochemical and pharmacokinetic properties of drug substances, such as the solubility and dissolution rate, bioavailability, particle morphology and size, tableting and compaction, melting point, physical form, biochemical and hydration stability, and permeability. In this feature review, we highlight some prominent examples of drug cocrystals which exhibit variable hardness/softness and elasticity/plasticity depending on coformer selection, improvement of solubility and permeability in the same cocrystal, increase of the melting point for solid formulation, enhanced color performance, photostability and hydration stability, and a longer half-life. Cocrystals of flavanoids and polyphenols can make improved pharmaceuticals and also extend to the larger class of nutraceuticals. The application of crystal engineering to assemble ternary cocrystals expands this field to drug-drug cocrystals which may be useful in multi-drug resistance, mitigating side effects of drugs, or attenuating/enhancing drug action synergistically by rational selection. The advent of new techniques for structural characterization beyond the standard X-ray diffraction will provide a better understanding of drug phases which are at the borderline of crystalline amorphous nature and even newer opportunities in the future. PMID- 27278110 TI - Can saliva testing replace blood measurements for health monitoring? Insights from a correlation study of salivary and whole blood glutathione in humans. AB - The feasibility of using saliva samples as diagnostic for health status is assessed. Although blood is regularly used for this purpose, an alternative non invasive route which yields equivalent clinical information is desirable. The non invasive saliva testing is validated by comparing its result to that of blood examination. In this investigation, we used glutathione as a paradigmatic example of a biomarker and diagnostic auxiliary. Correlation between the levels of total unbound glutathione, reduced and oxidized, in saliva and whole blood samples from healthy individuals is evaluated. Both salivary and blood glutathione were measured using an enzymatic kinetic assay which was improved to eliminate measurement errors arising from the variation in the enzyme activity from different batches. PMID- 27278111 TI - Lung cancer radiation therapy in Australia and New Zealand: Patterns of practice. AB - INTRODUCTION: The RANZCR Faculty of Radiation Oncology Lung Interest Cooperative (FROLIC) surveyed patterns of lung cancer radiation therapy practice for non small cell (NSCLC) and small cell lung cancer (SCLC) to evaluate current patterns of care and potential for improvement. METHODS: In October 2014, Radiation Oncologists (ROs) from all 62 departments in Australia and New Zealand were invited to a web-based survey directed at those treating lung cancer. Questions covered current radiation therapy practice as well as quality measures. RESULTS: Fifty-eight per cent of respondents used 4D-CT simulation. For curative treatment, 98% employed 3D-CRT and 34% intensity modulated radiotherapy (IMRT) techniques. Treatment verification was primarily performed using cone-beam CT (86%). In NSCLC, the commonest curative dose-fractionation regime was 60 Gy/30# (96%) and for palliative intent, 30 Gy/10# (76%). Forty-four per cent treated patients with stereotactic ablative body radiotherapy (SABR) and half treated central tumours with this technique. In fit patients with synchronous solitary brain metastases, 80% would give radical treatment. For curative-intent SCLC, 45 50.4 Gy/25-28# (61%) and 45 Gy/30#/1.5 Gy b.d. (48%) were used. Ninety-four per cent discussed lung cancer patients at multidisciplinary meetings. Contours were peer-reviewed by 74% and 50% for conventional fractionation and SABR respectively. CONCLUSION: A significant proportion of ROs did not have access to 4D-CT. The majority used 3D image verification and consistently prescribed evidence based doses. A significant number did not participate in peer-review of contours. Practice in IMRT and synchronous oligo-metastatic disease is variable and should be an area of future research. Utilising survey findings, FROLIC is developing consensus recommendations to guide practice. PMID- 27278112 TI - Identification of the novel HLA-DRB1*11:192 allele by sequence-based typing in Greece. AB - The new allele DRB1*11:192 exon 2 differs from the DRB1*11:01:01:01 by three substitutions. PMID- 27278113 TI - Structural disorder in metallic glass-forming liquids. AB - We investigated structural disorder by a new structural parameter, quasi-nearest atom (QNA), in atomistic configurations of eight metallic glass-forming systems generated through molecular dynamics simulations at various temperatures. Structural analysis reveals that the scaled distribution of the number of QNA appears to be an universal property of metallic liquids and the spatial distribution of the number of QNA displays to be clearly heterogeneous. Furthermore, the new parameter can be directly correlated with potential energy and structural relaxation at the atomic level. Some straightforward relationships between QNA and other properties (per-atom potential energy and alpha-relaxation time) are introduced to reflect structure-property relationship in metallic liquids. We believe that the new structural parameter can well reflect structure disorder in metallic liquids and play an important role in understanding various properties in metallic liquids. PMID- 27278114 TI - Texture Adaption in Dysphagia: Acceptability Differences Between Thickened and Naturally Thick Beverages. AB - PURPOSE: The aim of the study was to investigate differences in the acceptability between thickened and naturally viscous beverages. DESIGN: This was an exploratory, cross-sectional study. METHODS: One hundred twenty-eight healthy volunteers rated overall liking/disliking of a selection of each of three thickened drinks and three beverages of natural viscosity pre- and postconsumption. Mean ratings were subjected to statistical analysis done with t tests. FINDINGS: Although all naturally thick beverages evoked good expectations, there were significant differences in expected acceptance of thickened fluids concerning the kind of beverage. Postconsumption of naturally thick beverages were rated significantly better than thickened. CONCLUSIONS: The findings suggest an alternative offer of naturally thick drinks and waiver of thickening water when viscosity adaption is needed. CLINICAL RELEVANCE: The sufficient and safe oral fluid intake in dysphagia requires compliance to dietetic recommendations. Naturally thick beverages can contribute to increase the appeal of texture modified diet. PMID- 27278115 TI - Expression of VEGFR and PDGFR-alpha/-beta in 187 canine nasal carcinomas. AB - Radiotherapy represents the standard of care for intranasal carcinomas. Responses to tyrosine kinase inhibitors (TKIs) have been reported but data on expression of target receptor tyrosine kinases (rTKs) is limited. This study characterizes the expression of vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR)-alpha and PDGFR-beta in canine intranasal carcinomas. Histological samples from 187 dogs were retrieved. Immunohistochemistry was performed using commercially available antibodies. Expression of rTKs was classified into weak, moderate or intense and additionally recorded as cytoplasmic, membranous, cytoplasmic-membranous, nuclear or stromal. VEGFR was expressed in 158 dogs with predominantly moderate expression (36.9%) and a cytoplasmic-membranous expression pattern (70.9%). PDGFR-alpha was detected in 133 with predominantly weak expression (57.9%) and cytoplasmic pattern (87.9%). PDGFR-beta was identified in 74 patients with a predominantly moderate expression (17.6%) and cytoplasmic expression pattern (63.5%). Co-expression of rTKs was common. These results confirm expression of VEGFR, PDGFR-alpha and PDGFR beta in canine intranasal carcinomas and support the utility of TKIs. PMID- 27278116 TI - Building resilience in the face of adversity: navigation processes used by older lesbian, gay, bisexual and transgender adults living in Ireland. AB - AIMS AND OBJECTIVES: To explore resilience processes among older lesbian, gay, bisexual and transgender adults. BACKGROUND: Older lesbian, gay, bisexual and transgender identities have frequently been viewed from a deficit, vulnerability and pathological perspective; consequently, the natural resilience processes that underpin the lives of many older lesbian, gay, bisexual and transgender people goes unrecognised, with few studies focusing on the processes they use in building resilience. DESIGN: The design of the study is qualitative and exploratory. METHODS: Data were collected through in-depth, face-to-face interviews. Thirty-six lesbian, gay, bisexual and transgender people participated in the interviews. The mean age of the interview participants was 60.3 years. Thematic analysis was used to analyse the data. RESULTS: Nine processes were identified that enhanced participants resilience, namely: 'Making a decision to accept oneself and not be defined by lesbian, gay, bisexual and transgender identity'; 'Acquiring an empowering perspective'; 'Learning to let go and moving on'; 'Leaving oppressive social environments'; 'Experiencing affirming relationships with family and others'; 'Accessing formal supports'; 'Maintaining connections with lesbian, gay, bisexual, and transgender people'; 'Remaining positive and being thankful for life' and 'Remaining active and keeping busy'. These processes fostered the development of characteristics, such as: courage and strength; a positive sense of self and an optimistic outlook on life. CONCLUSION: This study provides evidence of the considerable strength among this group of people, highlighting how adversity has engendered in participants a set of resilience skills, adding to the emerging body of research into resilience and older lesbian, gay, bisexual and transgender people. RELEVANCE TO CLINICAL PRACTICE: Nurses not only need to be aware of the life histories of older lesbian, gay, bisexual and transgender people but they also need to assess their strengths and offer sensitive services that promote and support resilience among this population. PMID- 27278117 TI - Urinary tract infections in cats. Prevalence of comorbidities and bacterial species, and determination of antimicrobial susceptibility to commonly used antimicrobial agents. AB - OBJECTIVE: To investigate the prevalence of comorbidities (CM) in cats with urinary tract infections (UTIs), as well as the prevalence of bacterial species in cats with different CM and their antimicrobial susceptibility to the commonly used antibacterial agents doxycycline, trimethoprim-sulfamethoxazole (TMS), amoxicillin-clavulanic acid (AMC), cephalothin, and enrofloxacin. MATERIAL AND METHODS: A retrospective analysis of cats with positive urine cultures in the years 2003 to 2009 was performed. Cats were assigned to one of four groups: cats with systemic comorbidities (sCM), cats with indwelling urinary catheters (iUC), cats with local comorbidities (lCM), or cats without CM. To evaluate the potential effectivity of the antibiotics the antibacterial impact factors were calculated. RESULTS: A total of 194 cats with 219 isolates were included in the study. In 78.4% (152/194) of cats, a CM was identified; 49.5% had a sCM and 28.9% (56/194) had an iUC or a lCM. Cats with sCM were significantly older than cats in all other groups, and the proportion of female animals was higher in cats with sCM than in cats with iUC or lCM. More than half of the cats with sCM did not show clinical signs of lower urinary tract disease. The most commonly isolated bacteria species were Escherichia (E.) coli, Streptococcus spp., Staphylococcus spp., and Enterococcus spp. with a significantly higher proportion of E. coli isolates in cats with sCM and significantly higher proportions of Streptococcus and Staphylococcus spp. isolates in cats with iUC and other lCM. According to the antimicrobial impact factors bacterial isolates in cats with any CM were most likely susceptible to AMC and TMS. Isolates from cats with iUC and lCM had a lower likelihood to be susceptible to the tested antimicrobials than cats with sCM and cats without CM. CONCLUSION AND CLINICAL RELEVANCE: Relevant comorbidities for bacterial urinary tract infection were identified in the majority of cats in the present study. Cats with sCM often do not show clinical signs of lower urinary tract disease. AMC and TMS were the antimicrobial agents with the highest antimicrobial impact factor in this population of cats. PMID- 27278118 TI - Evidence of human infection by a new mammarenavirus endemic to Southeastern Asia. AB - Southeastern Asia is a recognised hotspot for emerging infectious diseases, many of which have an animal origin. Mammarenavirus infections contribute significantly to the human disease burden in both Africa and the Americas, but little data exists for Asia. To date only two mammarenaviruses, the widely spread lymphocytic choriomeningitis virus and the recently described Wenzhou virus have been identified in this region, but the zoonotic impact in Asia remains unknown. Here we report the presence of a novel mammarenavirus and of a genetic variant of the Wenzhou virus and provide evidence of mammarenavirus-associated human infection in Asia. The association of these viruses with widely distributed mammals of diverse species, commonly found in human dwellings and in peridomestic habitats, illustrates the potential for widespread zoonotic transmission and adds to the known aetiologies of infectious diseases for this region. PMID- 27278119 TI - The effect of dietary supplementation with rumen-protected methionine alone or in combination with rumen-protected choline and betaine on sheep milk and antioxidant capacity. AB - This study investigated the effects of dietary inclusion of rumen-protected methionine alone or in combination with rumen-protected choline and betaine on: (i) milk yield, chemical composition and fatty acids (FA) profile and (ii) blood plasma glutathione transferase (GST) activity of periparturient ewes. Furthermore, the oxidative stress indicators for measuring total antioxidant and free radical scavenging activity [ferric reducing ability of plasma (FRAP) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays] were also determined in plasma and milk of ewes. Thus, 45 ewes were divided into three equal groups. Each animal of the control group fed daily with a basal diet. The same diet was offered also in each animal of the other two groups. However, the concentrate fed to M group was supplemented with 2.5 g/kg rumen-protected methionine, while the concentrate fed to MCB group with 5 g/kg of a commercial product which contained a combination of methionine, choline and betaine, all three in rumen-protected form. The results showed that the M diet, compared with the control, increased significantly the ewe's milk fat and the total solids content. Likewise, a tendency for higher milk fat and total solids content in ewes fed the MCB diet was also observed. Both M and MCB diets had not noticeable impact on ewes milk FA profile. Significantly higher FRAP values in the blood plasma of ewes fed the MCB and in the milk of ewes fed with the M diet compared with the control were found. Additionally, significantly higher GST activity in the blood plasma of ewes fed the M diet, compared with the control, was observed. Moreover, a significant increase (by 20%) and a tendency for increase (by 16.72%) in the growth rate of lambs nursing ewes fed with M and MCB diets, respectively, compared to controls, were found. PMID- 27278120 TI - COP1 is downregulated in renal cell carcinoma (RCC) and inhibits the migration of RCC ACHN cells in vitro. AB - Constitutive photomorphogenic 1 (COP1) belongs to the COP-de-etiolated (DET) fusca (FUS) protein family and has been demonstrated to suppress prostate adenocarcinomas and other types of tumor, such as liver and gastric cancer. The present study investigated the expression of COP1 and its downstream factor, ets variant 1 (ETV1) in renal cell carcinoma (RCC) tissue samples, and evaluated the correlation of COP1 expression levels with the clinicopathological characteristics of RCC. In addition, the role of COP1 in the proliferation and migration of RCC ACHN cells was investigated. The results demonstrated significantly downregulated COP1 expression levels in the RCC intratumors, which was negatively associated with clinicopathological characteristics, such as tumor size, tumor-node-metastasis (TNM) stage and lymph node or distant metastasis. COP1 was demonstrated to markedly reduce the colony size of RCC ACHN cells, and inhibit the migration and invasion of ACHN cells. In addition, ETV1 and matrix metalloproteinase 7 (MMP7) mRNA and protein expression levels were significantly downregulated by the overexpressed COP1. Thus, the results of the present study demonstrate the reduced expression of COP1 and the upregulated expression of ETV1 in RCC tissue samples, which was associated with a high tumor-node-metastasis stage of RCC. Furthermore, the overexpression of COP1 in the RCC ACHN cells inhibited the migration and invasion of ACHN cells, and downregulated ETV1 and MMP7 expression levels. The present study demonstrated the tumor suppressive role of COP1 in RCC by inhibiting cell migration. PMID- 27278121 TI - Relationship of Early Spontaneous Type V Blood Pressure Fluctuation after Thrombolysis in Acute Cerebral Infarction Patients and the Prognosis. AB - We examined the relationship between an early spontaneous type V blood pressure fluctuation and the post-thrombolysis prognosis of patients with acute cerebral infarction. Patients were admitted consecutively. All patients were categorized into the type V blood pressure fluctuation group or non-type V blood pressure group. Their blood pressure was monitored before thrombolysis and until 6 h after thrombolysis. Baseline data and clinical outcomes were compared. Of 170 patients, 43 (25.2%) had an early type V blood pressure fluctuation. The National Institute of Health Stroke Scale (NIHSS) score before thrombolysis and 24 h after thrombolysis, and the modified Rankin scale score at 90 days differed significantly between the two groups (P < 0.05). Multiple logistic regression analysis showed that an unfavorable prognosis at 3 months was associated with the NIHSS score before thrombolysis (P = 0.000) but probably not with this blood pressure fluctuation (P = 0.058). An early spontaneous type V blood pressure fluctuation is common in patients with acute cerebral infarction who received venous thrombolysis, especially if they have a higher NIHSS score before thrombolysis. The type V blood pressure fluctuation may not influence patients' prognosis; however, this needs to be confirmed in future trials. PMID- 27278122 TI - Design of a photoelectrochemical device for the selective conversion of aqueous CO2 to CO: using mesoporous palladium-copper bimetallic cathode and hierarchical ZnO-based nanowire array photoanode. AB - An overall PEC CO2 conversion was firstly reported by integrating both the newly designed metal cathode and the n-type photoanode with functional nanostructures. The maximum Faradaic efficiency (FE) for CO is ca. 75% at -1.2 V with incident photon-to-current conversion efficiency (IPCE) value of 16% at 340 nm. PMID- 27278123 TI - Experimental arthritis: Helminth infection ameliorates arthritis. PMID- 27278124 TI - Inflammatory myopathies: Muscle pathology helps predict JDM outcomes. PMID- 27278125 TI - Systemic sclerosis: Tenascin C perpetuates tissue fibrosis. PMID- 27278126 TI - GWAS analysis implicates NF-kappaB-mediated induction of inflammatory T cells in multiple sclerosis. AB - To identify genes and biologically relevant pathways associated with risk to develop multiple sclerosis (MS), the Genome-Wide Association Studies noise reduction method (GWAS-NR) was applied to MS genotyping data. Regions of association were defined based on the significance of linkage disequilibrium blocks. Candidate genes were cross-referenced based on a review of current literature, with attention to molecular function and directly interacting proteins. Supplementary annotations and pathway enrichment scores were generated using The Database for Annotation, Visualization and Integrated Discovery. The candidate set of 220 MS susceptibility genes prioritized by GWAS-NR was highly enriched with genes involved in biological pathways related to positive regulation of cell, lymphocyte and leukocyte activation (P=6.1E-15, 1.2E-14 and 5.0E-14, respectively). Novel gene candidates include key regulators of NF-kappaB signaling and CD4+ T helper type 1 (Th1) and T helper type 17 (Th17) lineages. A large subset of MS candidate genes prioritized by GWAS-NR were found to interact in a tractable pathway regulating the NF-kappaB-mediated induction and infiltration of pro-inflammatory Th1/Th17 T-cell lineages, and maintenance of immune tolerance by T-regulatory cells. This mechanism provides a biological context that potentially links clinical observations in MS to the underlying genetic landscape that may confer susceptibility. PMID- 27278127 TI - Gene-disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections. AB - Interferon (IFN) lambda (IFN-lambda or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus. Notably, all these conditions have strong involvement of host innate immune responses. After the discovery of a deletion polymorphism that leads to the expression of a functional IFN-lambda4 as the prime 'functional' variant, the relevance of other polymorphisms regulating the expression of IFN-lambda3 is in doubt. Herein, I seek to critically address these issues and review the current literature to provide a framework to help further understanding of IFN-lambda biology. PMID- 27278128 TI - Phorbol ester-mediated re-expression of endogenous LAT adapter in J.CaM2 cells: a model for dissecting drivers and blockers of LAT transcription. AB - Linker for activation of T cells (LAT) is a raft-associated, transmembrane adapter protein critical for T-cell development and function. LAT expression is transiently upregulated upon T-cell receptor (TCR) engagement, but molecular mechanisms conveying TCR signaling to enhanced LAT transcription are not fully understood. Here we found that a Jurkat subline J.CaM2, initially characterized as LAT deficient, conditionally re-expressed LAT upon the treatment with a protein kinase C activator, phorbol 12-myristate 13-acetate (PMA). We took advantage of the above observation for studying cis-elements and trans-acting factors contributing to the activation-induced expression of LAT. We identified a LAT gene region spanning nucleotide position -14 to +357 relative to the ATG start codon as containing novel cis-regulatory elements that were able to promote PMA-induced reporter transcription in the absence of the core LAT promoter. Interestingly, a point mutation in LAT intron 1, identified in J.CaM2 cells, downmodulated LAT promoter activity by 50%. Mithramycin A, a selective Sp1 DNA binding inhibitor, abolished LAT expression upon PMA treatment as did calcium ionophore ionomycin (Iono) and valproic acid (VPA), widely used as an anti epileptic drug. Our data introduce J.CaM2 cells as a model for dissecting drivers and blockers of activation induced expression of LAT. PMID- 27278129 TI - Perception and Assessment of Verbal and Written Information on Sex and Relationships after Hematopoietic Stem Cell Transplantation. AB - This study aimed to investigate experiences of verbal and written information about sex and relationships among men and women treated with hematopoietic stem cell transplantation. The study also aimed to investigate the demand for information and assessment of the quality of written patient information material entitled "Sex and relationships in the treatment of blood diseases." Few studies exist that shed any light on the demand for information about sex and relationships on the part of patients with hematological diseases before, during, and after their treatment. A total of 216 patients undergoing treatment for malignant blood diseases between 2000 and 2010 participated in this study. Patients' experiences of information about sex and relationships, and their opinions about the written patient information, were assessed using a questionnaire created specifically for this study. Most patients (81 %) had not received information about sex and relationships from a healthcare professional. Almost 90 % of men felt that verbal information was important, compared with 82 % of women. The majority also held that written information was important. These results indicate that patients, regardless of gender, age, and treatment, consider oral and written information about sex and relationships to be important and that the healthcare system should provide the information. The written patient information was considered to play an important role in creating an opening for a conversation about a sensitive topic such as sexuality, and also as a source of reference and support for the patient and his/her partner. PMID- 27278130 TI - Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the Quintet Recruitment Intervention (QRI). AB - BACKGROUND: Pragmatic randomised controlled trials (RCTs) are considered essential to determine effective interventions for routine clinical practice, but many fail to recruit participants efficiently, and some really important RCTs are not undertaken because recruitment is thought to be too difficult. The 'QuinteT Recruitment Intervention' (QRI) aims to facilitate informed decision making by patients about RCT participation and to increase recruitment. This paper presents the development and implementation of the QRI. METHODS: The QRI developed iteratively as a complex intervention. It emerged from the National Institute for Health Research (NIHR) ProtecT trial and has been developed further in 13 RCTs. The final version of the QRI uses a combination of standard and innovative qualitative research methods with some simple quantification to understand recruitment and identify sources of difficulties. RESULTS: The QRI has two major phases: understanding recruitment as it happens and then developing a plan of action to address identified difficulties and optimise informed consent in collaboration with the RCT chief investigator (CI) and the Clinical Trials Unit (CTU). The plan of action usually includes RCT-specific, as well as generic, aspects. The QRI can be used in two ways: it can be integrated into the feasibility/pilot or main phase of an RCT to prevent difficulties developing and optimise recruitment from the start, or it can be applied to an ongoing RCT experiencing recruitment shortfalls, with a view to rapidly improving recruitment and informed consent or gathering evidence to justify RCT closure. CONCLUSIONS: The QRI provides a flexible way of understanding recruitment difficulties and producing a plan to address them while ensuring engaged and well-informed decision making by patients. It can facilitate recruitment to the most controversial and important RCTs. QRIs are likely to be of interest to the CIs and CTUs developing proposals for 'difficult' RCTs or for RCTs with lower than expected recruitment and to the funding bodies wishing to promote efficient recruitment in pragmatic RCTs. PMID- 27278131 TI - Puerarin attenuates inflammation and oxidation in mice with collagen antibody induced arthritis via TLR4/NF-kappaB signaling. AB - Puerarin is an important active ingredient in the root of kudzu vine due to its pharmacological properties. The aim of the present study is to contribute to the existing knowledge of the effect of puerarin in the attenuation of inflammation and oxidation in mice with collagen antibody-induced arthritis via toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-kappaB) signaling. Arthritis was induced using injection of anti-type II collagen antibodies. Treatment with puerarin was observed to significantly decrease clinical scoring of the collagen antibody-induced arthritis and suppress oxidative stress and the inflammatory response in mice. Furthermore, puerarin was demonstrated to inhibit mRNA expression of matrix metalloproteinase-9 and protein expression of TLR4 following collagen antibody-induced arthritis in mice. The effect of puerarin may be associated with the suppression of NF-kappaB activity in collagen antibody induced arthritis mice. Furthermore, upregulation of phosphorylated (p)-Janus kinase 2 and p-signal transducer and activator of transcription 3 protein expression was suppressed by puerarin. The results of the present study indicate, for the first time, the effect of puerarin to attenuate inflammation and oxidation in mice with collagen antibody-induced arthritis via TLR4/NF-kappaB signaling. PMID- 27278132 TI - Stressful work characteristics, health indicators and work behavior: the case of machine operators. AB - This article shows the results of research on psychosocial risks for a group of machine and plant operators (n = 1014) from the construction, chemical, energy, mining, metal and food industries in Poland. The Psychosocial Risk Scale designed in Nofer Institute of Occupational Medicine (NIOM) by Moscicka-Teske and Potocka was used to indicate the occurrence of general and specific occupational stressors and the level of their stressfulness. The results revealed that the studied machine and plant operators experience job context stress - related to working environment features concerning work organization - more frequently than job content stressors - related to the type of tasks they perform. Moreover, a correlation analysis between work features and the health and occupational functioning of the respondents revealed significant but weak relationships between the variables (from -0.08 to -0.23). Comparative analysis revealed the differences between the studied sectors. Such a comparison makes it possible to set goals for each sector and to attempt to improve the distinctive areas. PMID- 27278133 TI - Codon optimization of the adenoviral fiber negatively impacts structural protein expression and viral fitness. AB - Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon usage of adenoviral proteins by principal component analysis and assessed their codon adaptation to the host. We observed a general clustering of adenoviral proteins according to their function. However, there was a significant variation in the codon preference between the host-interacting fiber protein and the rest of structural late phase proteins, with a non-optimal codon usage of the fiber. To understand the impact of codon bias in the fiber, we optimized the Adenovirus-5 fiber to the codon usage of the hexon structural protein. The optimized fiber displayed increased expression in a non-viral context. However, infection with adenoviruses containing the optimized fiber resulted in decreased expression of the fiber and of wild-type structural proteins. Consequently, this led to a drastic reduction in viral release. The insertion of an exogenous optimized protein as a late gene in the adenovirus with the optimized fiber further interfered with viral fitness. These results highlight the importance of balancing codon usage in viral proteins to adequately exploit cellular resources for efficient infection and open new opportunities to regulate viral fitness for virotherapy and vaccine development. PMID- 27278134 TI - Expert position paper on prolonged dual antiplatelet therapy in secondary prevention following myocardial infarction. AB - The protective effect of dual antiplatelet therapy (DAPT) following acute coronary syndrome is undisputed, but its duration is subject of debate. Several studies show that prolonged therapy provides a clinical benefit in patients following acute coronary syndrome. The aim of this position paper authored by Austrian experts is to outline the current evidence and provide an overview of recent studies. It is also intended to serve as a practical guide to identify those patients who may benefit from prolonged DAPT. PMID- 27278136 TI - Powered robotic exoskeletons in post-stroke rehabilitation of gait: a scoping review. AB - Powered robotic exoskeletons are a potential intervention for gait rehabilitation in stroke to enable repetitive walking practice to maximize neural recovery. As this is a relatively new technology for stroke, a scoping review can help guide current research and propose recommendations for advancing the research development. The aim of this scoping review was to map the current literature surrounding the use of robotic exoskeletons for gait rehabilitation in adults post-stroke. Five databases (Pubmed, OVID MEDLINE, CINAHL, Embase, Cochrane Central Register of Clinical Trials) were searched for articles from inception to October 2015. Reference lists of included articles were reviewed to identify additional studies. Articles were included if they utilized a robotic exoskeleton as a gait training intervention for adult stroke survivors and reported walking outcome measures. Of 441 records identified, 11 studies, all published within the last five years, involving 216 participants met the inclusion criteria. The study designs ranged from pre-post clinical studies (n = 7) to controlled trials (n = 4); five of the studies utilized a robotic exoskeleton device unilaterally, while six used a bilateral design. Participants ranged from sub-acute (<7 weeks) to chronic (>6 months) stroke. Training periods ranged from single-session to 8-week interventions. Main walking outcome measures were gait speed, Timed Up and Go, 6 min Walk Test, and the Functional Ambulation Category. Meaningful improvement with exoskeleton-based gait training was more apparent in sub-acute stroke compared to chronic stroke. Two of the four controlled trials showed no greater improvement in any walking outcomes compared to a control group in chronic stroke. In conclusion, clinical trials demonstrate that powered robotic exoskeletons can be used safely as a gait training intervention for stroke. Preliminary findings suggest that exoskeletal gait training is equivalent to traditional therapy for chronic stroke patients, while sub-acute patients may experience added benefit from exoskeletal gait training. Efforts should be invested in designing rigorous, appropriately powered controlled trials before powered exoskeletons can be translated into a clinical tool for gait rehabilitation post-stroke. PMID- 27278138 TI - Corrigendum. PMID- 27278135 TI - Hypertension and coronary artery disease: epidemiology, physiology, effects of treatment, and recommendations : A joint scientific statement from the Austrian Society of Cardiology and the Austrian Society of Hypertension. AB - High blood pressure is a major modifiable risk factor for all clinical manifestations of coronary artery disease (CAD). In people without known cardiovascular disease, the lowest systolic (down to 90-114 mmHg) and the lowest diastolic (down to 60-74 mmHg) pressures are associated with the lowest risk for developing CAD. Although diastolic blood pressure is the strongest predictor of CAD in younger and middle-aged people, this relationship becomes inverted and pulse pressure shows the strongest direct relationship with CAD in people above 60 years of age.Pathophysiological mechanisms of blood pressure as a risk factor for CAD are complex and include the influence of blood pressure as a physical force on the development of the atherosclerotic plaque, and the relationship between pulsatile hemodynamics/arterial stiffness and coronary perfusion. Treatment of arterial hypertension has been proven to prevent coronary events in patients without clinical CAD. In patients with established CAD, the effect of blood pressure lowering per se is beneficial, probably more than specific drugs or drug classes. The important exceptions are beta blockers (BBs), which are superior to all other drug classes for use after a recent myocardial infarction. Blood pressure targets in patients with established CAD have created controversy in the light of the so-called J-curve phenomenon, which describes an increase in coronary events at lower diastolic blood pressures. One explanation for this observation is that perfusion of the left ventricle occurs predominantly during diastole, and that coronary autoregulation may be exhausted with low diastolic blood pressure in the setting of left ventricular hypertrophy and atherosclerotic narrowing of the epicardial coronaries. The worst situation is a high systolic blood pressure in the presence of a low diastolic blood pressure, both a hallmark of increased aortic stiffness. However, the lowering of systolic blood pressure is clearly beneficial in this setting, even at the price of further lowering diastolic pressure. Primary blood pressure goal in patients with established CAD is below 140/90 mmHg. Recent studies suggest that a lower systolic blood pressure may be appropriate, whereas caution is advised with diastolic blood pressure below 60 mmHg. PMID- 27278137 TI - Value-based procurement: Canada's healthcare imperative. AB - Value-based healthcare models are being adopted globally to maximize value for patients. Given that procurement is at the heart of purchasing value, value-based procurement goes hand in hand with value-based healthcare. Shifting procurement's traditional focus on short-term cost savings to a more holistic objective that includes health system performance and patient outcomes, giving preference to longer-term cost efficiencies, and working with suppliers to identify opportunities to develop more innovative products and services, is proving successful in leading jurisdictions. This article presents an overview of value within healthcare systems and how healthcare value-based procurement is being implemented across various jurisdictions. PMID- 27278139 TI - Precision medicine: Now, not when. AB - Precision medicine aims to fix what is wrong with today's healthcare: a lack of targeted interventions tailored to the person. It encompasses many aspects of health; chief among these is one's genetic profile. Researchers are making progress as gene-sequencing technologies get better and cheaper. Although there is cause for optimism, as several initiatives at Sunnybrook Research Institute show, scientific, systemic, and logistical challenges must be surmounted before advances can be integrated into the clinic. Despite these barriers, precision medicine is the only way forward. PMID- 27278158 TI - Comparative analysis of hepatic miRNA levels in male marathon mice reveals a link between obesity and endurance exercise capacities. AB - Dummerstorf marathon mice (DUhTP) are characterized by increased accretion of peripheral body fat with fast mobilization in response to mild physical activity if running wheels were included in their home cages. The obese phenotype coincides with elevated hepatic lipogenesis if compared to unselected controls. We now asked, if microRNA (miRNA) species present in the liver may contribute to the obese phenotype of DUhTP mice and if miRNAs respond to mild physical activity in our mouse model. Total RNA was extracted from livers of sedentary or physically active marathon mice and controls and analyzed by array hybridization or real-time PCR using locked nucleic acid probes. Pathway analysis of altered miRNA concentrations identified fatty acid biosynthesis as the most important target for the effects of miRNAs in the liver. A miRNA signature consisting of miR-21, 27, 33, 122, and 143 was present at higher abundance (p < 0.01) in the liver of sedentary or active DUhTP mice indicating involvement of miRNAs with hepatic lipogenesis. Furthermore, in protein lysates from the liver of DUhTP mice, significantly reduced concentrations of total and phosphorylated AKT and lower levels of phosphorylated AMPK were found (p < 0.05). Our results indicate active involvement of miRNAs in the control of hepatic energy metabolism and discuss effects on signal transduction as a potentially direct effect of miR-143 in the liver of DUhTP mice. PMID- 27278159 TI - MicroRNA-205 directly targets Kruppel-like factor 12 and is involved in invasion and apoptosis in basal-like breast carcinoma. AB - We investigated microRNAs (miRs) specific to its target gene and exerting distinct biological functions for basal-like breast carcinoma (BLBC). Total RNA was extracted and subjected to miR microarray and bioinformatics analysis. Based on the comprehensive analysis, expression of miRs including its target was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT PCR), western blot analysis and immunohistochemistry (IHC). Further functional analyses were conducted including proliferation, invasion and apoptosis. miR-205 was identified as downregulated (less than 0.5-fold) in BLBC relatively to normal control (NC). Gene ontology (GO) analysis suggested miR-205 may directly targeted Kruppel-like factor 12 (KLF12; degree=4). Luciferase assay revealed miR-205 directly targeted KLF12 through binding its 3'-untranslated region (3'-UTR; p=0.0016). qRT-PCR and western blot analysis showed miR-205 expression was low in cells (p=0.007) and tumor tissues (n=6; p=0.0074), and KLF12 RNA/protein was observed at high levels in cells (p=0.0026; p=0.0079) and tumor tissues (n=9; p=0.0083); knock-up of miR-205 increased its expression (p=0.0021) but reduced KLF12 RNA/protein levels (p=0.0038; p=0.009) in cells. Modulation of miR-205 expression by transfecting its mimics in cells, was involved in invasion (p=0.00175) and apoptosis (p=0.006). In conclusion, our results supported that miR-205 was a miR specific to BLBC which functioned as tumor suppressor gene through directly targeting and negatively regulating proto-oncogene KLF12. miR 205 dysregulation was involved in invasion and apoptosis. miR-205 and KLF12 provided a potential diagnosis biomarker and therapeutic approach for BLBC. PMID- 27278160 TI - From the 76th Conference of the Japan Society of Ultrasound in Medicine. PMID- 27278157 TI - Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se. AB - The effects of long-term use of nicotine per se on cancer risk, in the absence of tobacco extract or smoke, are not clearly understood. This review evaluates the strength of published scientific evidence, in both epidemiological and animal studies, for the potential carcinogenic effects of nicotine per se; that is to act as a complete carcinogen or as a modulator of carcinogenesis. For human studies, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a carcinogenic effect due to the limited information available. In animal studies, limited evidence suggests an association between long-term nicotine exposure and a lack of a complete carcinogenic effect. Conclusive studies using current bioassay guidelines, however, are missing. In studies using chemical/physical carcinogens or transgenic models, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a modulating (stimulating) effect on carcinogenesis. This is primarily due to the large number of conflicting studies. In contrast, a majority of studies provides sufficient evidence for an association between nicotine exposure and enhanced carcinogenesis of cancer cells inoculated in mice. This modulating effect was especially prominent in immunocompromized mice. Overall, taking the human and animal studies into consideration, there appears to be inadequate evidence to conclude that nicotine per se does or does not cause or modulate carcinogenesis in humans. This conclusion is in agreement with the recent US Surgeon General's 2014 report on the health consequences of nicotine exposure. PMID- 27278161 TI - Echocardiographically evaluated site of attachment of atrial myxoma may predict recurrence. AB - We explore the association between the site of attachment of nonfamilial left atrial myxoma and it's recurrence. Forty-three (11 male and 32 female; mean age, 55.9+/-13.6 years) of 49 consecutive patients with nonfamilial left atrial myxoma who had been evaluated with preoperative echocardiography, X were available for postoperative follow-up with transthoracic echocardiography, transesophageal echocardiography, or both, for an average period of 85.2+/-54.2 months (range, 6.5 to 215.5 months). We compared preoperative clinical and echocardiographic features of recurrent and nonrecurrent myxomas. Three (7%) of the 43 cases of atrial myxoma recurred at the same site after 24.1+/-7.6 months. Involvement of the mitral valve annulus or mitral valve leaflet (3 vs 0,p<0.001) was observed in the recurrent myxomas, but the two groups did not differ significantly in any other clinical features, laboratory data, or echocardiographic features of the recurrent and nonrecurrent myxoma. Preoperative echocardiographic observation of involvement of the mitral valve annulus or mitral valve leaflet may predict recurrence after surgery. Regular follow-up echocardiography was useful in the early detection of recurrence. PMID- 27278162 TI - Contrast-enhanced agent detection imaging: Early experience in hepatocellular carcinoma. AB - PURPOSE: To investigate the usefulness of contrast-enhanced Agent Detection Imaging in assessing intratumoral vasculature in hepatocellular carcinoma. MATERIALS AND METHODS: Fourteen hepatocellular carcinoma nodules in 11 patients were studied with contrast-enhanced Agent Detection Imaging, a wide-band color Doppler imaging method, employing, Levovist((r)), a microbubble contrast agent. High acoustic power was used with contrast-enhanced Agent Detection Imaging. Intermittent transmission of Agent Detection Imaging was performed at intervals of 200, 500, and 350 milliseconds in the early arterial phase (10 to 40 seconds), late vascular phase (1 to 3 minutes) and postvascular phase (5 to 7 minutes), respectively. The results were compared with those of three-phase dynamic CT. RESULTS: Intratumoral blood vessels in the early arterial phase and tumor parenchymal stain in the late vascular phase were depicted in 12 (88%) of the 14 hepatocellular carcinoma nodules, while all nodules were demonstrated as perfusion defect in the postvascular phase on contrast-enhanced Agent Detection Imaging. The results of Agent Detection Imaging, that were compared with those of dynamic CT, were all 100% : diagnostic sensitivity (12/12), specificity (2/2), and accurary (14/14). CONCLUSION: Contrast-enhanced Agent Detection Imaging is a promising method for depicting intratumoral vascularity in hepatocellular carcinoma. PMID- 27278163 TI - Value of new contrast harmonic technique for detecting tumor vascularity in hepatocellular carcinoma: Preliminary results. AB - PURPOSE: To investigate the value of a new wide-band contrast harmonic imaging method in depicting intratumoral vascularity in hepatocellular carcinoma. MATERIALS AND METHODS: Twenty-two patients with 28 hepatocellular carcinoma nodules evaluated with Contrast Harmonic Echo, a new wide-band harmonic imaging method, using Levovist((r)) as a contrast-enhancing agent. Intermittent imaging was carried out in the early arterial phase for 10 to 40 seconds, in the late vascular phase for 1 to 2 minutes, and in the postvascular phase for 5 to 7 minutes. Subtraction images were obtained using the multishot method during the late vascular phase. The ability of Contrast Harmonic Echo imaging to detect vascularity in hepatocellular carcinoma was compared to that of unenhanced color Doppler imaging by analzing results obtained using dynamic CT as a gold standard. RESULTS: Contrast harmonic Echo imaging detected intratumoral vessels, tumor parenchymal stain, and perfusion defect in the early arterial phase, the late vascular phase, and the postvascular phase, respectively. In the late vascular phase, the subtraction image clearly delineated the tumor parenchymal strain. Intratumoral vascularity was detected in 25 (89%) of the hepatocellular carcinoma nodules by Contrast Harmonic Echo, compared with 15 (54%) when color Doppler imaging was used (p<0.05). The diagnostic sensitivity, specificity, and accuracy of Contrast Harmonic Echo were 96.1%, 100% and 96.4%, respectively, corresponding to results obtained using dynamic CT. CONCLUSION: Contrast Harmonic Echo imaging is superior to unenhanced color Doppler imaging in depicting intratumoral vessels and parenchymal stain, and agrees closely with results obtained with three-phase dynamic CT. PMID- 27278164 TI - Optimization of enhancement of therapeutic efficacy of ultrasound: Frequency dependent effects on iodine formation from KI-starch solutions and ultrasound induced killing of rat thymocytes. AB - We investigated liberation of iodine from solutions of KI-starch and cell lysis of rat thymocytes in argon-and nitrous oxide-saturated aqueous solutions induced by ultrasound at frequencies of 38 and 500 kHz and 1 and 2 MHz. Iodine was liberated in argon-saturated solutions exposed to ultrasound at 38 kHz, 500 kHz, and 1 MHz but not at 2 MHz. Lysis occurred in argon-saturated solutions at all four frequencies, but only at 38 kHz in nitrous oxide-saturated cell suspensions. No iodine was liberated in the other nitrous oxide-saturated samples. Relative ratio of the chemical effect versus 70-percent cell survival (an example of the physical effect) was, in order of frequency, 500 kHz>1.0 MHz>38 kHz>2.0 MHz. Partial protection was observed for cell lysis and cell viability after sonication with 500 kHz in argon-saturated solution containing cysteamine, a free radical scavenger. These results suggest that the chemical effects of ultrasound are prominent at specific frequencies, and that free radicals induced by ultrasonic cavitation partially affect lysis and the loss of viability of rat thymocytes. PMID- 27278165 TI - Study of the automated breast tumor extraction using 3D ultrasound imaging: The usefulness of depth-width ratio and surface-volume index. AB - We applied quantitative parameters in three-dimensional ultrasonic images to distinguish benign from malignant breast tumors in 29 benign cases including 8 cysts and 21 fibroadenomas, and 32 malignant cases including 23 ductal carcinomas, 2 special types of carcinoma, 1 malignant lymphoma and 6 others. This procedure involved simultaneously acquiring video data from real-time ultrasonic images and recording the original position and orientation of the probe. Both sets of data were fed directly into a desktop computer. Fuzzy reasoning and relaxation techniques were use to automatedly extract the shape of the tumor and render it in three dimensions. We then evaluated three parameters: 2D-D/W, the so called depth-width ratio measured in B-mode images: 3D-D/W; and the S/V index ([surface area](3)/36pi [volume](2)) calculated from the three-dimensional volume extracted with this system. All three parameters were significantly higher in the malignant group (averages: 0.81, 0.64, and 11.3, respectively) than in the benign group (averages: 0.62, 0.47, and 3.78, respectively). All three parameters were thus found to be useful in differentiating the two groups. PMID- 27278166 TI - The efficacy of cibenzoline for reducing the left ventricular pressure gradient of hypertrophic obstructive cardiomyopathy: A case report. AB - A 46 year-old man with hypertrophic obstructive cardiomyopathy (HOCM) was referred to this clinic complaining of shortness of breath. His symptoms remained even after he had been treated with bisoprolol, lisinopril, and verapamil. We started treating him with cibenzoline, instead of verapamil. Continuous-wave Doppler examination revealed a marked decrease from 95.9 mm Hg to 8.8 mmHg in the left ventricular outflow tract pressure gradient after administration of cibenzoline, and the symptom disappeared. The electrical axis of the electrocardiogram deviated from +53 to +95 degrees, and the QRS interval was increased from 0.095 to 0.114 seconds. By the M-mode echocardiogram, the interventricular septum was observed moved paradoxically in the early, systolic phase. We suggest the possibility that cibenzoline modifies intraventricular conduction and causes asynchronous contraction of the left ventricle, resulting in decrease in the left ventricular outflow tract pressure gradient. PMID- 27278167 TI - Changes in the aortic and pulmonary diameters in a fetus with hypoplastic left heart syndrome. AB - We diagnosed hypoplastic left heart syndrome in a 26-week-old fetus using fetal echocardiography. Color Doppler ultrasonography was helpful for evaluating the structural abnormalities. The diameters of the aorta and the pulmonary artery were measured periodically from 26 to 38 weeks of gestation. Aortic diameter was below the normal range throughout gestation. The diameter of the pulmonary artery was normal at 26 weeks of gestation but gradually dilated and was abnormally dilated after the 36th week of gestation. Here we discuss the cause of enlarged pulmonary artery in fetal hypoplastic left heart syndrome. PMID- 27278168 TI - Primary pancreatic lymphoma forming a giant mass in a short period: A case report. AB - A 69 year old man with chief complaints of vomiting and nausea was referred to our hospital. Ultrasonographic examination on 19 May 1998 showed a hypoechoic homogeneous mass 6 cm in diameter in the head of the pancreas. Degree of intravascular infiltration was angiographically mild despite its large size. Tumor-marker levels were normal. On 9 August 1998, however, ultrasonography showed the mass to have rapidly grown (10 cm in diameter) including a heterogeneous internal structure. The mass had a linear or branching signal pattern. PMID- 27278170 TI - Analysis of Eight Isoflavones in Radix Puerariae by MEEKC: Comparison on Three Different Oil Phases. AB - In this study, three different oil phases include 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide (BMPy[NTf2]), 1-butyl-3-methylimidazolium hexafluorophosphate (BMImPF6) and n-octane were compared for the MEEKC analysis (SDS as surfactant and n-butanol as co-surfactant) of eight isoflavones from pueraria. The investigated isoflavones can be well separated by all of those three microemulsion systems after careful optimization, and the MEEKC with n octane as the oil phase was the best choice (good symmetry and high resolutions of peaks with short analysis time) for the analysis. The optimum conditions of MEEKC method were as follows: 70 mM SDS, 0.7 M n-butanol and 0.5% (w/v) n-octane in 10 mM sodium tetraborate (STB) at pH 8.5, applied voltage was 23 kV and cassette temperature was set at 30 degrees C. And then the developed method was fully validated (limit of detection, limit of quantification, intraday precision, interday precision and recovery) and successfully applied to determine the eight analytes in three Radix Puerariae samples. In addition, although the MEEKC with classic oil phase (n-octane) showed better results for isoflavones analysis in this study, the MEEKC with ionic liquids (BMPy[NTf2] and BMImPF6) also showed great separation potential for analytes, which may be further applied in the analysis of other natural products. PMID- 27278172 TI - Changes in the medical system in Japan. PMID- 27278171 TI - Concurrent NP-HPTLC Determination of Shikonin and beta,beta-Dimethylacryl Shikonin in Arnebia benthamii. AB - Naphthoquinones are important class of molecules found as a natural red color pigments in roots of Arnebia benthamii (Wall. ex G. Don) L M. Johnston. The aim of present investigation is to develop and validates a simple, cost-effective and reliable method for quantification of these compounds. Therefore, a normal phase high performance thin-layer chromatography (NP-HPTLC) method for concurrent determination of shikonin and beta,beta-dimethylacryl shikonin in A. benthamii was established. Method development of naphthoquinones in the methanol extract was done using hexane-ethyl acetate-methanol (40:7.5:2.5, v/v/v) solvent system at 520 nm. The developed method showed good band separation for shikonin (Rf, 0.37) and beta,beta-dimethylacryl shikonin (Rf, 0.58). The linearity ranged between 100 and 8,000 ng spot(-1) with an average recovery of >97% in both cases. The results showed reproducible intraday and interday precision (<2.0% RSD) in quantification of naphthoquinones. The limits of detection are 12.96 and 14.65 ng spot(-1) while the limits of quantification are 39.27 and 44.39 ng spot(-1) for shikonin and beta,beta-dimethylacryl shikonin, respectively. The developed method is reliable, fast, easy to follow and economic in concurrent assessment of shikonin and beta,beta-dimethylacryl shikonin in A. benthamii root samples. In addition, it seems to be first report for identification and quantification of beta,beta-dimethylacryl shikonin from the A. benthamii. PMID- 27278174 TI - Monitoring of hepatic artery resistance index and optimal timing of liver transplantation for biliary atresia. AB - PURPOSE: Biliary atresia (BA) is diagnosed by ultrasound (US) examination of the hepatic artery and gallbladder. This study was designed to assess the usefulness of the hepatic artery resistance index (HRI) measured by Doppler ultrasonography (DUS) for prognostication of liver viability in children with BA. METHODS: Seventeen patients with non-correctable BA were examined by US and DUS before and after hepatoenterostomy to evaluate hepatic artery dynamics. RESULTS: Dilatation of the hepatic artery was demonstrated in all 17 patients. US of the gallbladder showed hypogenesis in seven patients. Preoperatively, all 17 BA patients had an HRI of <1.0. Six of the 17 patients underwent liver transplantation. Four of the six had an HRI of >0.9, and the HRI decreased after the procedure. All patients were alive at the time of writing. CONCLUSIONS: Regular US examinations are helpful for diagnosis of BA and for detecting patients at high risk. A prospective study is required to determine the optimal frequency of assessment. PMID- 27278173 TI - Use of accumulation images obtained by arterial-phase contrast-enhanced harmonic grayscale ultrasonography to evaluate tumor vessels in focal nodular hyperplasia and other hepatic tumors. AB - PURPOSE: To evaluate the usefulness of accumulation images obtained by arterial phase contrast-enhanced harmonic grayscale ultrasonography for examining tumor vessels in focal nodular hyperplasia and other hepatic lesions. METHODS: After injecting a galactose-palmitic acid contrast agent, we used conventional contrast enhanced harmonic grayscale ultrasonography to scan 8 focal nodular hyperplasia lesions, 21 hepatocellular carcinomas, 2 cholangiocellular carcinomas, 12 hepatic metastases, 17 hemangiomas, and 2 angiomyolipomas. We then accumulated and superimposed consecutive conventional images (accumulation images) and compared them with corresponding conventional images to evaluate serial images of hepatic tumor vessels. RESULTS: Serial tumor vessel findings obtained from accumulation images were superior to those obtained from conventional images in 51 (77%) of the 66 various hepatic lesions examined. Evidence of the spoke-wheel artery pattern in 2 of the 8 focal nodular hyperplasia lesions was equivocal in the conventional images, but accumulation images clearly depicted serial images of spoke-wheel arteries, clearly indicating a diagnosis of focal nodular hyperplasia. Accumulation images allowed the diagnosis of two additional focal nodular hyperplasia lesions that had not been correctly diagnosed as focal nodular hyperplasia from conventional images. CONCLUSION: Accumulation images obtained by arterial-phase contrast-enhanced harmonic grayscale ultrasonography are useful in evaluating hepatic tumor vessels, especially spoke-wheel arteries, which specifically indicate focal nodular hyperplasia. PMID- 27278175 TI - Three-dimensional sonographic volume measurement of the fetal cerebellum. AB - PURPOSE: The objective of this longitudinal study was to evaluate the growth of the fetal cerebellum in normal pregnancy by using three-dimensional ultrasound. METHODS: Three-dimensional sonographic examinations were performed for 13 appropriate-for-gestational-age fetuses. Fetal cerebellar volume was measured every 2 to 3 weeks after 20 weeks of gestational age until delivery. The common multiplanar technique was used to calculate the fetal cerebellar volume. RESULTS: A curvilinear relationship was found between gestational age and cerebellar volume (R(2) = 78.6%, P < 0.0001), and normal ranges of cerebellar volume measurements for estimating the growth of the fetal cerebellum during normal pregnancy were generated. The data gathered in this study were fairly comparable with previous data obtained using three-dimensional ultrasound. However, the normal ranges of cerebellar volume that we determined were relatively wide throughout pregnancy. CONCLUSIONS: Our findings suggest that a standard curve for fetal cerebellar volume using three-dimensional ultrasound can play a role in the evaluation of normal cerebellar growth in the fetus. However, we do cast doubt on the reliability and reproducibility of cerebellar volume measurement using three dimensional ultrasound. Further studies involving a larger sample size and another technique (the rotational method with VOCAL) would be needed to confirm these findings. PMID- 27278176 TI - Improved imaging of the carotid artery in the short-axis plane by a mechanical scanning ultrasonic probe. AB - To image the intima-media complex of the carotid artery in a wider region, a method for measuring cross-sectional images in the arterial short-axis plane is presented. Using the proposed mechanical scanning system for an ultrasonic probe, cross-sectional images of a silicon rubber tube and a human carotid artery are measured in basic experiments and in in vivo experiments, respectively. These experiments show that this method successfully images the short-axis cross sections. Using the method proposed in this article, B-mode images in the short axis plane can be accurately measured in a wider region than is possible with conventional methods. PMID- 27278177 TI - Evaluation of left ventricular diastolic function using color kinesis. AB - PURPOSE: Color kinesis (CK) is a real-time echocardiographic technique based on acoustic quantification that yields regional and global information by tracking and color-encoding endocardial motion. The aim of this study was to determine the feasibility and usefulness of diastolic CK images with ICK software to objectively assess global and regional left ventricular (LV) diastolic function. Accordingly, diastolic properties obtained from CK images were compared with conventional Doppler echocardiographic indices. METHODS: We studied 56 subjects who underwent echocardiographic evaluation in our laboratory for assessment of cardiac structure and function. Criteria for inclusion included the presence of normal sinus rhythm and adequate two-dimensional echocardiographic imaging. Exclusion criteria were (1) all types of arrhythmias, (2) pericardial effusion, (3) heart rates <55 or >90 beats/min, (4) abnormal interventricular septal motion caused by right ventricular pressure or volume overload, (5) moderate to severe mitral or aortic regurgitation, and (6) mitral valve stenosis. Using pulsed Doppler echocardiography, peak velocities during rapid filling (E) and atrial contraction (A) were measured, and the E/A ratio and deceleration time of the E wave velocity (DT) were calculated. The time-velocity integral (TVI) of the E wave (TVI-R), A wave (TVI-A), and rapid-filling fraction (TVI-R/TVI-R+TVI-A) was measured. The early diastolic mitral annular velocity (Ea) was measured by tissue Doppler. The 56 subjects were divided into the following three groups: (1) an impaired relaxation group consisting of 30 patients with normal ejection fraction and a mitral inflow pattern with a reduced E/A ratio (E/A < 1.0); (2) a pseudonormal group consisting of 18 patients with a mitral inflow pattern with an increased E/A ratio (E/A > 1.0), an increased E/Ea ratio (E/Ea 10), and no shortened DT (?140 ms) [patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 8), and aortic valve stenosis (n = 2) were included in this group); and (3) a restrictive group consisting of eight patients with a mitral inflow pattern with an increased E/A ratio (E/A >1.5), an increased E/Ea ratio (E/Ea ?10), and a shortened DT (<140 ms) [patients with DCM (n = 5) and HCM (n = 3) were included in this group]. As a control group, 20 normal subjects (30 +/- 18 years) were selected on the basis of having high-quality echocardiographic images. Diastolic CK images were obtained from the LV midpapillary short-axis view. The analysis of CK diastolic images was performed by using ICK software. The CK-diastolic index (CK-DI) was defined as the degree of LV segmental expansion during the first 30% of diastole, expressed as a percentage. The mean CK-DI was calculated from the average CK-DI of six LV segments. RESULTS: No relationship was observed between mean CK-DI and rapid filling fraction in any of the study subjects (r = -0.092, P > 0.2). Mean CK-DI was significantly lower in the restrictive group (34.2% +/- 4.3%) compared with the normal group (70.6% +/- 7.4%), the impaired relaxation group (50.5% +/- 7.7%), and the pseudonormal group (42.3% +/- 7.5%). The reduction of mean CK-DI was found to be associated with the progression of LV diastolic dysfunction. CONCLUSION: We conclude that the analysis of diastolic CK by using ICK software is a useful technique that can be applied to quantitative evaluation of LV global diastolic function. PMID- 27278178 TI - Development of an automatic Doppler flow signal detection system: variability of pulmonary and aortic peak flow velocity. AB - PURPOSE: Automatic Doppler flow signal detection systems can provide beat-to-beat information for large blood vessels. We have developed new equipment for automatic measurement of Doppler flow signals. The reliability of the system was examined, and the variability of aortic and pulmonary peak flow velocity was determined. METHODS: We measured peak flow velocity using a newly developed system in healthy volunteers and patients with atrial fibrillation. Analysis of variability of peak flow velocity was performed with maximal entropy methods. RESULTS: In Bland-Altman plots, the mean and standard deviation (SD) of differences in aortic peak flow velocities between the automatic and manual measurements were 0.22 +/- 0.75 cm/s and 0.85 +/- 0.38 cm/s, respectively, in five normal volunteers. Moreover, less than 5% of the plotted points were beyond +/- 2 SD of the differences. Furthermore, good reproducibility was demonstrated using Bland-Altman plots and Pearson's correlation analysis. Identical reliability was obtained in patients with atrial fibrillation. The same results were obtained for pulmonary peak flow velocity. In five healthy subjects, aortic and pulmonary peak flow showed standard deviations of 7.2 +/- 2.4 and 3.8 +/- 0.6 cm/s, respectively, and coefficients of variation of 6.1% +/- 1.0% and 5.1% +/- 1.1%, respectively, in time-domain variability. Similarly, frequency-domain variability was obtained for both peak flow velocities. CONCLUSION: The present study demonstrated the reliability of a newly developed automatic Doppler flow signal detection system. Using this system, the present study demonstrated for the first time aortic and pulmonary peak flow velocity variability. The present analytical methods may have considerable potential for studying aortic and/or pulmonary flow variability in connection with cardiac performance and prognosis of cardiac disease. PMID- 27278179 TI - Hyalinizing trabecular tumor of the thyroid gland: characteristic features on ultrasonography. AB - We report a case of hyalinizing trabecular tumor of the thyroid gland and describe the characteristic ultrasonographic features of this tumor. This was a rare tumor of follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. The tumor had an irregular shape, a delicately jagged border, and hypoechoic and heterogeneous internal echoes on B mode ultrasonography. Very rich intratumoral blood flow, the so-called "tumor inferno" was evident on power Doppler ultrasonography. In the clinical management of thyroid nodules, clinicians should be aware of this peculiar type of thyroid tumor and its characteristic ultrasonographic findings. PMID- 27278180 TI - A case of solitary intraductal papilloma of the breast coexisting with ductal carcinoma in situ (DCIS). AB - A 54-year-old woman was referred to this institution because of spontaneous bloody discharge from the nipple of her left breast in July 2003. Physical examination revealed no mass, but minimal pressure on the mammary gland exuded a bloody discharge from the nipple. No lymph node swelling was recognized in the axillary or subclavicular regions. Mammography and magnetic resonance imaging revealed mastopathy. Ultrasonography on the immersion method demonstrated a dilated duct with an irregular, solid, hypoechoic mass immediately behind the nipple. Fine-needle aspiration cytology showed the mass to be an intraductal tumor. Carcinoembryonic antigen (CEA) concentration of the nipple discharge was 400 ng/ml. Preoperatively, she was diagnosed as intraductal solitary papilloma, and endoscope-assisted microdochectomy was carried out under general anesthesia. The tumor was 10.5-10.6 mm in diameter and had developed from the posterior wall of the duct adjacent to the nipple. The tumor contained a small solid area in which a two-cell layer of epithelium was missing, and thus solitary papilloma coexisting with ductal carcinoma in situ (DCIS) was diagnosed. Solitary intraductal papilloma coexisting with carcinoma is rare; cases of DCIS are exceptionally rare. Follow-up for 3 years has revealed no evidence of recurrence. PMID- 27278181 TI - Hemodynamic changes in a patient with esophageal varices after endoscopic injection sclerotherapy evaluated by endoscopic color Doppler ultrasonography. AB - A 46-year-old man with alcoholic cirrhosis was admitted to our hospital for treatment of high-risk esophageal varices in February 2000. Images of the esophageal varices, paraesophageal veins and palisade veins were obtained by endoscopic color Doppler ultrasonography (ECDUS) before endoscopic injection sclerotherapy (EIS). Prophylactic EIS was performed six times per week for esophageal varices, and EIS was continued until the esophageal varices were completely eradicated. In July 2002, endoscopy revealed esophageal varices graded as Cb, F1, Lm, and RC(-), and color flow images of the palisade veins (hepatofugal flow), esophageal varices, and a developed paraesophageal vein were obtained with ECDUS. In April 2003, endoscopy showed esophageal varices graded as Cb, F1, Lm, and RC(-), and color flow images of the palisade veins and esophageal varices were obtained using ECDUS. The blood in the palisade veins flowed in an alternate direction on color flow images, and pulsatile waves were delineated at the gastroesophageal junction. In January 2004, endoscopy revealed esophageal varices graded as F0 and RC(-), and pulsatile waves were delineated in the lower esophagus with ECDUS. However, the esophageal varices and palisade veins had disappeared from color flow images. In conclusion, ECDUS was useful for evaluating hemodynamic changes after EIS. PMID- 27278182 TI - Efficacy of color Doppler ultrasonography for the diagnosis of duodenal varices successfully treated with percutaneous transhepatic obliteration. AB - We treated a 74-year-old woman who complained of tarry stool. Neither endoscopic examination of the upper gastrointestinal tract nor colonoscopy revealed any finding indicative of bleeding, and (99m)Tc-HSA-D pool scintigraphic imaging showed no accumulation of blood in the digestive tract. Small tortuous collateral veins were observed on computed tomography (CT) in the distal third portion of the duodenum. Color Doppler ultrasonography obtained color flow images of varices in the distal third portion of the duodenum indicating turbulent flow, and color flow imaging showed the outflow vessel from duodenal varices. Duodenoscopy revealed tortuous varices, with erosions and blue in appearance, in the same area. Percutaneous transhepatic portography was carried out 18 days after the treatment of ascites, and hepatofugal blood flow was confirmed in the pancreatic duodenal vein originating near the junction between the splenic and inferior mesenteric veins with the passage of contrast medium into the duodenal varices, which drained into the left ovarian vein. We performed selective catheterization into the afferent vein of the varices, and injected 8 ml of a 5% solution of ethanolamine oleate containing iopamidol. Microcoil embolization using steel coils was added because the therapeutic effect resulting after the relatively rapid washout of sclerosant was insufficient. CT and color Doppler ultrasonography showed absence of blood flow in the varices 1 week after the therapy. This patient has had no episodes of rebleeding in the 24 months after therapy. Color Doppler ultrasonography was useful in diagnosing this case of duodenal varices and in evaluating therapeutic effect. PMID- 27278183 TI - Hemodynamic evaluation of rectal varices by color Doppler ultrasonography: a case report. AB - A 69-year-old man with liver cirrhosis was admitted to our hospital with general fatigue. Colonoscopy revealed risky red color sign-positive enlarged tortuous rectal varices. Endoscopic injection sclerotherapy (EIS) was performed three times weekly using 5% ethanolamine oleate with iopamidol; the total amount of sclerosant was 7 ml. Images of rectal varices and the outflowing vessel from rectal varices were obtained via color Doppler ultrasonography before EIS, and fast Fourier transform analysis showed a continuous flow with a frequency shift of 276.6 Hz. We successfully performed EIS for this patient, having effective varicealography. After EIS, colonoscopy revealed shrinkage of the varices in the rectum, and color Doppler indicated an extreme decrease of blood flow in the rectal varices. In conclusion, color Doppler is a useful noninvasive modality for detecting rectal varices and for evaluating the therapeutic effects of EIS. PMID- 27278184 TI - Use of hand-held ultrasonography to confirm the correct placement of a central venous catheter tip. AB - To avoid severe complications resulting from malpositioning of a central venous catheter, removal and recannulation of the catheter may be necessary, thus wasting medical equipment and increasing stress on the patient. Therefore, central venous catheters should be inserted correctly the first time. We tested whether real-time hand-held ultrasound-guided confirmation of the location of the tip of a central venous catheter inserted from the femoral vein could reduce the rate of malpositioning. Catheters were inserted using conventional methods for 65 patients, and using ultrasound guidance for 29 patients. For the latter group, when a central venous catheter was inserted, the ultrasound examiner first identified its tip located dorsal to the liver in the inferior vena cava and then fixed the catheter in position. We considered a central venous catheter to be malpositioned when its tip appeared in neither the inferior vena cava nor the right atrium-inferior vena cava junction in X-rays. Flexed or inverted catheters were also considered to be malpositioned. We compared the malpositioning rates for the ultrasound and conventional groups. Malpositioning was identified for two (6.9%) patients in the ultrasound group and 19 (29.2%) patients in the conventional group. The relative risk of ultrasound-guided versus conventional catheter insertion was 0.23 (95% confidence interval, 0.09-0.62). Our data suggest that real-time ultrasound monitoring is useful for avoiding malpositioning of central venous catheters inserted from the femoral vein. PMID- 27278185 TI - Tissue structure of arterial wall revealed with elasticity imaging. PMID- 27278186 TI - Color Doppler determination of gastric content in a patient with gastric carcinoma accompanied by pyloric stenosis. PMID- 27278188 TI - Epoch-making sonographic images changed our world. PMID- 27278187 TI - A novel method to reduce noise in electroretinography using skin electrodes: a study of noise level, inter-session variability, and reproducibility. AB - To determine the feasibility of recording reproducible electroretinograms (ERGs) with skin electrodes using a new ERG system. Seventeen healthy volunteers were studied. The dark-adapted, bright-flash ERGs were recorded with a new ERG recording system (LE-4000, Tomey, Nagoya, Japan) in which the stimulus alternated between the eyes every 15 s, and each eye was stimulated eight times. The active skin electrode was placed on the lower eyelids of both eyes. The voltage changes of the non-stimulated eye were subtracted from that of the stimulated eye to try to increase the signal-to-noise ratio for eight stimulus cycles. The noise levels were measured from 12 subjects with and without the subtraction steps. ERGs were also recorded on five different days from five subjects, and the coefficient of variation (CV) and the intra-class correlation coefficients (ICCs) were calculated. The noise level without the subtraction step was 18.4 +/- 8.4 MUV, and it was significantly reduced to 13.8 +/- 4.0 MUV with the subtraction step (P = 0.001). Reproducible ERGs were obtained from each subject, and the average CV for the five subjects was 6.1 % for the a-wave amplitude, 7.7 % for the b-wave amplitude, and 7.7 % for the sum of the oscillatory potential (OP) amplitude. The ICC was 0.76 for the a-wave amplitude, 0.68 for the b-wave amplitude, and 0.72 for the sum of the OPs amplitude. These findings indicate that our new ERG recording methods shows noise reduction and good reproducibility with low inter session variability even with skin electrodes. PMID- 27278189 TI - Proposal of a parametric imaging method for quantitative diagnosis of liver fibrosis. AB - PURPOSE: Coming up with a quantitative diagnosis method for liver fibrosis using ultrasound would be highly significant. To permit tissue characterization using the characteristics of the echo signal such as power spectrum, texture parameters, local attenuation, and statistical characteristics, the relation between complicated scatterer structures and the echo signal must be understood. METHODS: In this study, we analyzed the property of the echo amplitude envelope using computer-simulated scatterer models. These models mimicked various liver conditions to evaluate our quantitative parametric imaging methods. Statistical echo characteristics changed with the density of the heterogeneous scatterer buried in a speckle. RESULTS: The new analysis method for a medium in which some tissues are embedded was proposed in consideration of analysis results from computer simulations. In the new method, it is possible to eliminate the influence of a cyst or veins and to detect the existence of fibers more clearly than in previous methods. PMID- 27278190 TI - Comparing enhancement and washout patterns of hepatic lesions between sonazoid enhanced ultrasound and contrast-enhanced computed tomography. AB - PURPOSE: To compare sonazoid-enhanced ultrasound (SEUS) and contrast-enhanced computed tomography (CECT) enhancement and washout patterns in hepatic lesions. METHODS: Enhancement and washout patterns on SEUS were compared with those on CECT for 61 lesions. There were 36 hepatocellular carcinomas, three intrahepatic cholangiocarcinomas, three metastatic lesions, eight focal nodular hyperplasias, two angiomyolipomas, and nine undetermined benign lesions. Diagnosis was based on histopathology, or CECT and tumor markers, or findings on 2-year follow-up. RESULTS: All 61 lesions (100%) showed arterial enhancement on both SEUS and CECT. The "washout/no washout" agreement between SEUS and CECT for the 61 lesions was 93.4% (kappa coefficient: 0.816). Of the 42 malignant lesions, 38 lesions (90.5%) showed washout on both SEUS and CECT. The remaining four malignant lesions, of which three lesions contained fibrosis (two intrahepatic cholangiocarcinomas and one scirrhous hepatocellular carcinoma), showed washout on SEUS but not on CECT. For the 19 benign lesions, agreement between SEUS and CECT was 100% (kappa coefficient: 1), with seven lesions showing washout with both methods and 12 lesions showing no washout with both methods. CONCLUSION: The overall concordance rate between SEUS and CECT was good, but some differences were seen in the washout patterns of malignant lesions. PMID- 27278191 TI - Sonographic hemodynamic evaluation of spleno-renal shunt using the Valsalva maneuver. AB - PURPOSE: The purpose of this study was to assess the characteristic features of hemodynamic changes in portal venous hypertension with spleno-renal shunt on conventional B-mode and color Doppler imaging before and after the Valsalva maneuver. MATERIALS AND METHODS: A total of 11 patients with portal venous hypertension underwent conventional B-mode and color Doppler ultrasound during follow-up examinations. Sonographic imaging of the splenic vein and the left renal vein was performed before and after the Valsalva maneuver. RESULTS: In the six patients with spleno-renal shunt formation, dilated left renal veins were depicted after the Valsalva maneuver. In the five patients without spleno-renal shunt, there was no apparent dilatation of the left renal vein either before or after the Valsalva maneuver. In all six patients with spleno-renal shunt, color flow mapping of the left renal veins was emphasized during the Valsalva maneuver. In the five patients without spleno-renal shunt formation, there were no apparent changes on color flow mapping of the left renal vein before or after the Valsalva maneuver. CONCLUSION: The sonographic findings of the splenic vein and the left renal vein on conventional B-mode and color Doppler imaging before and after the Valsalva maneuver are useful for diagnosis of spleno-renal shunt and for grading the hemodynamic changes caused by spleno-renal shunt. PMID- 27278192 TI - Breast mass classification on sonographic images on the basis of shape analysis. AB - PURPOSE: To evaluate the efficiency of novel shape features for classification of benign and malignant sonographic breast masses. METHODS: Mass regions were extracted from the region of interest (ROI) sub-image by applying a segmentation algorithm based on the level set method. Six features (difference area with five features of mass pixel number viewed at different angles) were then extracted for further classification. A multilayered perceptron neural network (MLP) classifier was used to classify breast mass. The leave-one-case-out procedure was used on a database of 81 pathologically proved breast sonographic images of patients (47 benign cases and 34 malignant cases) to evaluate our method. RESULTS: The classification results showed overall accuracy was 93.83%, sensitivity 91.18%, specificity 95.74%, positive predictive value 93.94%, and negative predictive value 93.75%. CONCLUSION: The experimental results showed that this diagnostic system with the features proposed can improve the positive rate of biopsies, provide a second opinion for physicians, and be used as a useful tool for mass classification. PMID- 27278194 TI - Change in cervical length in cases resulting in threatened preterm labor. AB - PURPOSE: To determine the predisposing changes in cervical length (CL) and the critical range of CL in which significant uterine contractions emerge resulting in threatened preterm labor (TPL). METHODS: Sixty-eight uncomplicated singleton pregnancies where the CL was <25 mm before 31 weeks were divided into cases with TPL (n = 23) or without (n = 45). CL and uterine contractions were monitored sequentially starting between 16 and 20 weeks. The gestational ages when a CL of <25 or <15 mm was first observed, the interval between these two measurements, and the CL value at TPL diagnosis were analyzed retrospectively. RESULTS: (1) The gestational ages when a CL of <25 and <15 mm was first detected were lower in the TPL group (25 (median); 18-30 (range) and 28; 25-33 weeks, respectively) than in the non-TPL group (27; 20-30 and 33; 26-35 weeks; P = 0.030 and P < 0.001). (2) The interval between the two measurements was shorter in the TPL group (2.5; 0-15 weeks) than in the non-TPL group (5.5; 0-13 weeks, P = 0.034). (3) The CL value at TPL diagnosis was 13 mm (median), ranging from 7 to 18 mm. CONCLUSION: Cases with early onset and subsequent rapid CL shortening before 31 weeks resulted in TPL when CL decreased below the range 7-18 mm. PMID- 27278193 TI - Evaluation of pelvic floor function by transabdominal ultrasound in postpartum women. AB - PURPOSE: To investigate the relationship between displacement of the bladder base and genitohiatal distance during voluntary contractions of pelvic floor muscles in postpartum women. METHODS: Twenty women (age 34.7 +/- 4.4 years, BMI 21.1 +/- 3.2 kg/m(2)) at about 6 weeks after a vaginal delivery were studied. Displacement of the bladder base and genitohiatal distance were measured by transabdominal and transperineal ultrasound, respectively. RESULTS: Displacement of the bladder base was significantly correlated with shortening of genitohiatal distance (r = 0.772, p < 0.001). The intraclass correlation coefficient of the three measurements in each woman was 0.796 for displacement of the bladder base. There was no significant difference in terms of displacement of the bladder base between continent women and incontinent women. CONCLUSION: This study suggests a strong positive correlation between displacement of the bladder base and shortening of genitohiatal distance during voluntary contractions of pelvic floor muscles in postpartum women. Measurement of displacement of the bladder base by transabdominal ultrasound can be helpful for evaluating pelvic floor function in postpartum women. PMID- 27278195 TI - Establishment of reference ranges for ductus venosus waveform indices in the Japanese population. AB - OBJECTIVE: To establish reference ranges for ductus venosus waveform indices in the Japanese population. METHODS: In this retrospective cross-sectional study, 791 singleton fetuses of healthy Japanese couples were examined from January 2004 to January 2008. Reference ranges for ductus venosus waveform indices were constructed from cross-sectional data obtained at between 18 and 41 weeks of gestation. RESULTS: With a success rate of 84%, a total of 667 measurements in 791 women were eligible for analysis. The median pulsatility index (PI) of fetal ductus venosus decreased from 0.54 at 18 weeks of gestation to 0.30 at 41 weeks of gestation. The median end-diastolic velocity/peak systolic velocity (a/S) of the ductus venosus increased from 0.56 at 18 weeks of gestation to 0.76 at 41 weeks of gestation. CONCLUSIONS: In this study, we established reference ranges for the PI and a/S of the ductus venosus in the Japanese population, which differed slightly from other published reference data. The results will be useful for further studies to determine the validity of the clinical importance of the ductus venosus for at-risk fetuses. PMID- 27278196 TI - Placental multiple chorionic cysts in maternal scleroderma. AB - We present a case of a pregnant woman with scleroderma (Ssc) whose placenta showed multiple chorionic cysts and severe fibrotic changes and large infarcted areas at the maternal side. Fetal growth was appropriate for gestational age and amniotic fluid volume was normal, but fetal tachycardia, loss of variability, and late deceleration were detected by non-stress test at 29 weeks of gestation. She was diagnosed as having non-reassuring fetal status and delivered a female baby who weighed 1092 g (Apgar score 6/9) by Caesarean section. Placental surface cysts are rare findings and their effect on pregnancy is poorly understood, but an association with intrauterine growth restriction (IUGR) has been reported. This is the first report of a pregnant woman with scleroderma showing multiple placental cysts. PMID- 27278197 TI - Large pseudocyst of the umbilical cord detected in the second trimester. AB - We present a case of a large umbilical cord cyst detected at 21 weeks of gestation. Serial ultrasonographic examination revealed a single umbilical artery and progression of the cystic mass. A 2,842-g male infant was delivered at 37 weeks of gestation, and we confirmed that the umbilical cord cyst was a pseudocyst in our pathological examination. This case demonstrated an uneventful course of pregnancy despite the large umbilical cord pseudocyst. PMID- 27278198 TI - Ultrasonographic findings for breast carcinoma with osteoclast-like giant cells. PMID- 27278200 TI - Editor's Note. PMID- 27278199 TI - Erratum to: Ultrasonographic findings for breast carcinoma with osteoclast-like giant cells. PMID- 27278201 TI - Laparoscopic Microwave Liver Ablation and Portal Vein Ligation: An Alternative Approach to the Conventional ALPPS Procedure in Hilar Cholangiocarcinoma. AB - BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a new procedure aimed at promoting the overgrowth of small future liver remnants (FLR). The role of ALPPS in hilar cholangiocarcinoma (h CCA) is currently considered marginal because liver split in the presence of bile duct obstruction increases postoperative morbidity and mortality (Schadde et al. in Ann Surg 260:829-836,2014; Nadalin et al. in Z Gastroenterol 52:35-42,2014). Virtual liver split (Gall et al. in Ann Surg 261:e45-e46,2015) could improve the outcome of ALPPS in h-CCA. METHODS: A 64-year-old woman with a type IIIA h-CCA without evidence of vascular involvement had a small FLR (FLR/body weight: 0.47 cm3/kg). After bilateral percutaneous biliary drainage (PBD) and bilirubin normalization, the patient was planned for laparoscopic step 1 ALPPS using microwave ablation (MWA). Because of possible challenge in hilar dissection in this tumor type, robotic assistance was preferred to conventional laparoscopy for step 1. RESULTS: The patient recovered promptly from step 1, with a 68 % increase in the volume of FLR by postoperative day (POD) 10 (FLR/body weight of 0.79 cm3/kg). On POD 15, the patient underwent open right hepatectomy with en bloc resection of the caudate lobe, bile duct bifurcation, and extrahepatic biliary duct (T2N1M0R0). Estimated blood loss was negligible during step 1 and 150 mL during step 2. The patient recovered well. Chemotherapy was started 6 weeks after ALPPS stage 2, and was well tolerated and full course. Twenty months after resection the patient is alive, well, and disease-free. CONCLUSIONS: Laparoscopic ALPPS (Machado et al. in Ann Surg 256:e13,2012) and MWA on the intended split line (Gringeri and Boetto in Ann Surg 261:e42-e43,2015) have been recently described. The combination of these techniques with PBD allowed successful ALPPS in a patient with h-CCA. PMID- 27278202 TI - National Evaluation of Hospital Performance on the New Commission on Cancer Melanoma Quality Measures. AB - INTRODUCTION: To increase adherence to cancer management guidelines, the Commission on Cancer (CoC) developed and approved five melanoma quality measures in 2015. Our objectives were to evaluate formally the national performance of these melanoma measures and to examine patient, tumor, and hospital characteristics associated with adherence. METHODS: From the National Cancer Data Base (2012), patients with invasive, nonmetastatic melanoma were identified. Inclusion and exclusion criteria were based on the CoC definition for each measure. Patient-level and hospital-level adherence rates were calculated for the five measures. A hospital was deemed "compliant" if it met the CoC standard, which requires 80 % of patients to receive the measure-specific recommended care. Patient, tumor, and hospital characteristics potentially associated with higher likelihood of adherence at the patient-level were estimated using hierarchical random-effects logistic regression models. RESULTS: A total of 31,598 patients from 1343 hospitals were examined. Patient-level adherence rates varied from 31.6 % (Measure 5: >=10 axillary lymph nodes removed/examined) to 72.6 % (Measure 1: sentinel lymph node biopsy (SLNB) appropriateness measure). Hospital-level adherence rates, ranged from 19.3 % of hospitals (N = 538 hospitals for Measure 5) to 44.8 % of hospitals (N = 1090 hospitals for Measure 3: completion lymph node dissection after positive SLNB). No hospital-level factors (e.g., teaching status) were consistently associated with better adherence. CONCLUSIONS: National adherence rates to the five new CoC melanoma quality metrics are low, and most hospitals would not meet the CoC requirement of 80 % adherence. Feedback for performance of these measures to hospitals, decisions support tools, and educational initiatives are needed to improve guideline adherence. PMID- 27278203 TI - Impact of Neoadjuvant Chemoradiation on Short-Term Outcomes for Esophageal Squamous Cell Carcinoma Patients: A Meta-analysis. AB - BACKGROUND: Neoadjuvant chemoradiation (NCRT) has emerged as a component of the standard treatment for esophageal squamous cell carcinoma (SCC). The primary benefit of NCRT is an improvement in long-term survival; however, the impact of NCRT on short-term outcomes is unclear. METHODS: A comprehensive electronic literature search was performed via the MEDLINE (PubMed), Cochrane Library, and Google Scholar databases through November 2015 for the inclusion of randomized controlled trials (RCTs) that evaluated short-term outcomes of patients administered NCRT followed by surgery compared with surgery alone for resectable esophageal SCC. The main outcome measures were postoperative mortality and morbidity. A meta-analysis was performed using random-effects models to calculate odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS: Eight RCTs were included, for a total of 1058 patients. Meta-analysis of the overall postoperative mortality and cardiopulmonary complication rates showed that there was a significant increase for patients administered NCRT followed by surgery compared with surgery alone (OR 1.87, 95 % CI 1.07-3.28, p = 0.03, number of patients needed to harm = 33.3; and OR 2.12, 95 % CI 1.03-4.35, p = 0.04, respectively). Dropout before surgery was higher for patients in the NCRT followed by surgery group compared with patients in the surgery-alone group. NCRT has no statistically impact on anastomosis and other complications compared with surgery alone. CONCLUSIONS: NCRT for esophageal SCC significantly increases postoperative mortality and cardiopulmonary complications. PMID- 27278204 TI - Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer. AB - BACKGROUND: To investigate the prognostic significance of altered breast cancer susceptibility gene 1 (BRCA1) and p53 expression in triple-negative breast cancer (TNBC). METHODS: Immunohistochemical expression of BRCA1 and p53 was examined in the tumor tissues of 465 TNBC cases and relations were sought with clinicopathological features and patient survival. RESULTS: Loss of BRCA1 expression was found in 29.5% (137/465) of TNBCs. Positive expression of p53 was observed in 49.9% (232/465). Patients with loss of BRCA1 expression had a tendency to have higher rate of lymph node metastasis (p = 0.075). An association between p53 expression and high histological grade was observed (p = 0.039). TNBC patients with loss of BRCA1 expression had a tendency to have poorer overall survival (OS) than those positive for BRCA1 (p = 0.09). TNBC patients with positive p53 expression showed better OS than those with p53 negativity (p = 0.001). In terms of combined expression patterns, significantly poorer overall survival (OS) was observed for BRCA1-negative/p53-negative TNBCs and best OS for BRCA1-positive/p53-positive TNBCs (p = 0.005). CONCLUSIONS: Combined expression patterns of BRCA1 and p53 could serve as useful prognostic markers in TNBC. PMID- 27278205 TI - Overweight causes left ventricular diastolic asynchrony and diastolic dysfunction: a study based on speckle tracking echocardiography in healthy subjects. AB - BACKGROUND: Left ventricular (LV) diastolic dysfunction is often observed in healthy subjects and can be a cause of heart failure with preserved ejection fraction (EF). We aimed to investigate the role of LV diastolic asynchrony as a cause of diastolic dysfunction in healthy subjects. METHODS: In 40 healthy subjects, two-dimensional speckle tracking imaging (2DSTI) was performed to measure the peak early diastolic longitudinal strain rates (Esr) of the apical, mid-ventricular, and basal segments of the septum and posterior wall. A mean value of the Esr of the 6 segments (mEsr) was calculated. The time from aortic valve closure to the Esr was measured for each segment, and the standard deviation (SDTEsr) was calculated. The peak global early diastolic strain rate (gEsr) was measured with a region of interest (ROI) on the whole LV myocardium. LV flow propagation velocity (FPV) was measured using conventional Doppler techniques. RESULTS: SDTEsr was not correlated with age, but was significantly correlated with body mass index (BMI) (r = 0.41, p < 0.01). Although no significant correlation was observed between mEsr and FPV, gEsr and SDTEsr significantly correlated with FPV (r = 0.41, p < 0.01; r = -0.54, p < 0.001). As a result of the multiple regression analysis, SDTEsr was the single determinant of FPV. CONCLUSIONS: Diastolic asynchrony, associated with overweight but not with aging, may contribute to diastolic dysfunction in healthy subjects. PMID- 27278207 TI - Long-term follow-up of a rare calcified cardiac tumor: a case report. AB - We describe a case of cardiac masses (high- and iso-echoic mass) which were detected by echocardiography in a 57-year-old man with cerebral infarction. Because he refused both biopsy and surgery, the patient was treated with an anticoagulant and antibiotic in our outpatient clinic. During 3-year follow-up, the iso-echoic mass disappeared and the high-echoic mass did not change. Thus, we considered the iso-echoic mass a thrombus and the high-echoic mass a benign tumor. Cardiac computed tomography revealed that the high-echoic mass had extensive calcifications like phleboliths, and magnetic resonance imaging pattern coincided with that of hemangiomas. We conclude that the benign tumor/high-echoic mass might be a vascular malformation. PMID- 27278206 TI - Single-beat determination of global longitudinal speckle strain in patients with atrial fibrillation. AB - BACKGROUND: Although global left ventricular (LV) systolic function is an important determinant of outcome, the assessment of global longitudinal speckle strain (GLS) in patients with atrial fibrillation (AF) is unreliable because of beat-to-beat variation. Previous studies have confirmed that LV contractility of each irregular beat is predicted from the ratio of preceding R-R (RR1) to pre preceding R-R (RR2) intervals, and the value when the intervals are equal (RR1/RR2 = 1) estimates the average value of LV contractility. The aim of this study was to assess the clinical feasibility of an index that is obtained on the basis of the RR1/RR2 ratio for the estimation of GLS in patients with AF. METHODS: We evaluated the RR1/RR2 ratio for the measurement of GLS with apical 4 chamber views in 20 patients with AF. We obtained the GLS for >=13 cardiac cycles, and the relationship between each GLS at a given cardiac beat and the RR1/RR2 ratio was evaluated by linear regression analysis. The value of GLS at RR1/RR2 = 1 was compared with the measured average value. RESULTS: The GLS showed a significant correlation with the RR1/RR2 ratio (r = -0.80). The calculated value of GLS at RR1/RR2 = 1 was quite similar to the average value (-10.17 +/- 2.1 % vs. -10.06 +/- 2.1 %). The GLS of a single beat with identical RR1 and RR2 intervals showed a significant correlation compared with the measured average value over all cardiac cycles (r = 0.94, y = 0.90x - 0.97). CONCLUSIONS: The GLS at RR1/RR2 = 1 allows the LV systolic parameter to be accurately evaluated during AF and obviates the less reliable process of averaging multiple irregular beats. PMID- 27278208 TI - The dramatic 3D IVUS imaging demonstrating a dislodged coronary stent. AB - A 78-year-old female underwent cardiac evaluation because she had presented with typical effort-induced chest pain. Coronary angiography revealed severe stenoses in the proximal left anterior descending coronary artery (LAD) and ostium of the diagonal branch. Then, a stent was deployed in the LAD covering the takeoff of the branch. Next, we tried to deploy an additional stent in the branch, but the new stent was stripped off the balloon platform. We demonstrate here the dramatic 3D intravascular ultrasound (IVUS) images of a dislodged stent, indicating that 3D IVUS imaging should allow the precise location and statement of lost stent. PMID- 27278209 TI - Three-dimensional transesophageal echocardiography in the diagnosis of atrial septal aneurysm with patent foramen ovale in a patient with ventricular septal defect. AB - We present a case of a rare combination of ventricular septal defect and atrial septal aneurysm (ASA) with a patent foramen ovale (PFO) in a 57-year-old female. She was referred to our hospital for the treatment of irregular palpitation and exertional shortness of breath. Two-dimensional transesophageal echocardiography (2D-TEE) with color Doppler imaging demonstrated an ASA with two lines of shunt flows. Three-dimensional transesophageal echocardiography (3D-TEE) could clearly visualize the morphology of the PFO in the surgeon's view and demonstrated a crescent-shaped opening of the PFO. 3D-TEE appears to be a more accurate modality than 2D-TEE for the assessment of PFO. PMID- 27278210 TI - Biventricular stress-induced (Tako-tsubo) cardiomyopathy complicated by right ventricular thrombus. AB - Tako-tsubo cardiomyopathy is a syndrome characterised by transient ventricular dysfunction most commonly involving the left ventricle. Complications include congestive heart failure, hypotension and intracardiac thrombus formation predisposing to thromboembolic events. Right ventricular involvement may also occur but is usually less marked, with complications of right ventricular dysfunction not commonly seen. PMID- 27278211 TI - A case with double-chambered right ventricle and left ventricular-right atrial communication (Gerbode defect): potential pitfall for Eisenmenger syndrome. AB - The ventricular septal defect (VSD) can rarely be associated with other malformations such as double-chambered right ventricle (DCRV) in which hypertrophied muscle bundles divide the right ventricle into two chambers causing progressive obstruction (Mao et al., Asia Pac J Thorac Cardiovasc Surg 5:14-17, 1996). Most VSDs close spontaneously by apposition of the tricuspid leaflets, but the process is rarely disrupted, resulting in communication between left ventricle and right atrium called Gerbode defect [Cho et al., J Cardiovasc Ultrasound 19(3):148-151, 2011]. Hence, the Gerbode defect involves potential misinterpretation of its high-velocity shunt as pulmonary hypertension. Here we present a case with DCRV and Gerbode defect initially misdiagnosed to have Eisenmenger syndrome. PMID- 27278212 TI - Systolic left ventricular apical bulging after biventricular pacing mimicking takotsubo cardiomyopathy. AB - Resolution of the issue of nonresponsiveness to cardiac resynchronization therapy (CRT) remains crucial to the successful treatment of conduction disturbances in heart failure. In this study, a patient with refractory heart failure including left bundle branch block was treated via surgical CRT. The epicardial left ventricular (LV) lead, implanted using thoracoscopic guidance, was unexpectedly located on the apical side. Echocardiographic findings of the LV motion mimicked takotsubo cardiomyopathy. The LV lead was successfully re-implanted along a lateral branch of the cardiac vein using an endovascular approach, resulting in restored contractility and reversal of the LV remodeling. PMID- 27278213 TI - Congenital ductus arteriosus aneurysm. PMID- 27278214 TI - Non-bacterial thrombotic endocarditis associated with Trousseau's syndrome. PMID- 27278215 TI - Metastases of hepatocellular carcinoma to the heart. PMID- 27278216 TI - Expression of organic cation transporter 1 (OCT1): unique patterns of indirect regulation by nuclear receptors and hepatospecific gene regulation. AB - The organic cation transporter 1 (OCT1) is the dominant carrier of organic cationic drugs and some positively charged endogenous compounds into hepatocytes. OCT1 has unique expression pattern. It has the highest expression among drug transporters in normal human hepatocytes with large interindividual variability, but it has negligible expression in other tissues or their tumors. Nowadays, it is clear that the regulation of SLC22A1 gene encoding OCT1 transporter is rather complex and that transactivation with hepatocyte nuclear factor 4alpha (HNF4alpha) and CCAAT-enhancer-binding protein (C/EBPs) transcription factors as well as epigenetic regulation contribute to its unique hepatocyte-specific expression pattern. Unfortunately, species- and tissue-specific regulation of OCT1 and its orthologs as well as significant down-regulation in most immortalized cell lines hamper the study of SLC22A1 gene regulation. In the current review, we summarize our current understanding of human OCT1 transporter hepatic gene regulation and we propose potential post-transcriptional regulation by predicted miRNAs. We also discuss in detail recent findings on indirect regulation of the transporter via farnesoid X receptor (FXR), glucocorticoid receptor and pregnane X (PXR) receptor, which point out to potential novel mechanisms of xenobiotic-transporting and drug-metabolizing proteins regulation in the human liver as well as to potentially novel drug-drug interaction mechanisms. We also propose that comprehensive understanding of mechanisms of SLC22A1 gene regulation could direct research for other drug transporters and drug-metabolizing enzymes highly expressed in hepatocytes and controlled by HNF4alpha or other liver-enriched transcription factors. PMID- 27278217 TI - Daclatasvir for the Treatment of Chronic Hepatitis C: A Critique of the Clinical and Economic Evidence. AB - The National Institute for Health and Care Excellence (NICE) invited the manufacturer of daclatasvir (Bristol-Myers Squibb) to submit clinical and cost effectiveness evidence for daclatasvir in combination with other medicinal products within its licensed indication for the treatment of chronic hepatitis C, as part of the Institute's single technology appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents the ERG's critical review of the evidence presented in the company submission in the context of a description of the company submission, and the resulting NICE guidance. The main clinical effectiveness data for daclatasvir in combination with sofosbuvir (daclatasvir + sofosbuvir) were derived from two uncontrolled open-label trials. Among patients with genotype 1 infection, 98-100 % of patients had a sustained virologic response at week 12 (SVR12), overall. Among genotype 3 patients, between 85 and 100 % had SVR12 across patient populations and regimens. The main evidence for daclatasvir + pegylated interferon-alpha and ribavirin (PR) came from one randomised controlled trial comparing daclatasvir + PR with PR in patients with genotype 4. This found an SVR12 rate of 82 % in previously untreated patients. Serious adverse event rates associated with daclatasvir were low. The lack of comparative trial evidence for daclatasvir + sofosbuvir and many of the comparators defined in the NICE scope meant that established methods for comparing interventions either directly via head-to-head trial comparisons or via adjusted indirect comparisons were not feasible. Comparisons of SVR rates were therefore largely based on unadjusted estimates drawn from individual trial arms and subgroups of individual trial arms. The ERG concluded that, despite limited evidence, daclatasvir in combination with other treatments appeared to be associated with a high SVR rate. Daclatasvir + sofosbuvir was unlikely to be inferior to comparator treatments in genotype 1 patients; but, due to limited evidence, the relative efficacy of daclatasvir and other treatments in genotype 3 and 4 patients or patients with compensated cirrhosis was uncertain. The economic evaluation compared daclatasvir + sofosbuvir and daclatasvir + PR with a wide range of NICE-approved treatments for hepatitis C. The company submission focused on a series of subgroups defined by disease severity (METAVIR fibrosis stage F3, compensated cirrhosis), genotype and treatment history. In the cost-effectiveness analysis, daclatasvir-containing regimens were cost effective at a L20,000-L30,000 per QALY threshold in the following F3 populations: genotype 1 treatment naive (Incremental cost effectiveness ratio [ICER] = L19,739/QALY) and treatment experienced (L15,687/QALY) and genotypes 1, 3 and 4 interferon ineligible or intolerant (L5906-L9607/QALY depending on subgroup). In patients with cirrhosis, daclatasvir containing regimens were not cost effective. The ERG found the company's economic analyses to be highly uncertain and in places biased. However, the ERG found that daclatasvir-containing regimens were cost effective in certain populations with significant fibrosis, and following new analyses by the company after a price reduction, in certain populations with cirrhosis, including patients who were not eligible for or who were intolerant to interferon therapy. The NICE Appraisal Committee's preliminary recommendation was that daclatasvir + sofosbuvir should be available as an option in genotype 1 and 4 patients with significant fibrosis but without cirrhosis, who had either been treated previously or were ineligible or intolerant to interferon. In response to the preliminary recommendation, the manufacturer submitted additional information including comparator SVR rates and a revised confidential price. Following this, the Committee expanded its original recommendation in its Final Appraisal Determination. The recommendation was expanded to include daclatasvir + sofosbuvir as an option for patients with significant fibrosis but without cirrhosis (in previously untreated patients with genotype 1, and genotype 3 patients ineligible or intolerant to interferon) and genotype 1, 3 and 4 cirrhotic patients who were ineligible or intolerant to interferon. Daclatasvir + PR was also recommended as an option for genotype 4 patients who had significant fibrosis or compensated cirrhosis. PMID- 27278219 TI - The Tensile Behavior of High-Strength Carbon Fibers. AB - Carbon fibers exhibit exceptional properties such as high stiffness and specific strength, making them excellent reinforcements for composite materials. However, it is difficult to directly measure their tensile properties and estimates are often obtained by tensioning fiber bundles or composites. While these macro scale tests are informative for composite design, their results differ from that of direct testing of individual fibers. Furthermore, carbon filament strength also depends on other variables, including the test length, actual fiber diameter, and material flaw distribution. Single fiber tensile testing was performed on high strength carbon fibers to determine the load and strain at failure. Scanning electron microscopy was also conducted to evaluate the fiber surface morphology and precisely measure each fiber's diameter. Fiber strength was found to depend on the test gage length and in an effort to better understand the overall expected performance of these fibers at various lengths, statistical weak link scaling was performed. In addition, the true Young's modulus was also determined by taking the system compliance into account. It was found that all properties (tensile strength, strain to failure, and Young's modulus) matched very well with the manufacturers' reported values at 20 mm gage lengths, but deviated significantly at other lengths. PMID- 27278218 TI - Label-free Chemical Imaging of Fungal Spore Walls by Raman Microscopy and Multivariate Curve Resolution Analysis. AB - Fungal cell walls are medically important since they represent a drug target site for antifungal medication. So far there is no method to directly visualize structurally similar cell wall components such as alpha-glucan, beta-glucan and mannan with high specificity, especially in a label-free manner. In this study, we have developed a Raman spectroscopy based molecular imaging method and combined multivariate curve resolution analysis to enable detection and visualization of multiple polysaccharide components simultaneously at the single cell level. Our results show that vegetative cell and ascus walls are made up of both alpha- and beta-glucans while spore wall is exclusively made of alpha glucan. Co-localization studies reveal the absence of mannans in ascus wall but are distributed primarily in spores. Such detailed picture is believed to further enhance our understanding of the dynamic spore wall architecture, eventually leading to advancements in drug discovery and development in the near future. PMID- 27278220 TI - Laparoscopic ventral hernia repair using a novel intraperitoneal lightweight mesh coated with hyaluronic acid: 1-year follow-up from a case-control study using the Hernia-Club registry. AB - PURPOSE: A case-control study was performed to compare laparoscopic ventral hernia repair (LVHR) using the Ventralight STTM lightweight surgical mesh with LVHR using other types of mesh. METHODS: Adult patients undergoing intraperitoneal implantation of Ventralight STTM during LVHR (Ventralight STTM group; VG) over a 2-year period (2011-2013) were identified from the prospective French Hernia-Club registry. Patients undergoing elective LVHR using other types of intraperitoneal mesh in the first semester of 2013 formed the control group (CG). Patient, hernia and surgical characteristics, and postoperative outcomes after 8 days, 1 month, and 1 year were compared between the two groups. RESULTS: The VG comprised 90 LVHRs in 85 patients, and the CG 86 LVHRs in 81 patients. Patient, hernia and surgical characteristics were similar between the two groups, apart from the method of mesh fixation and the number of procedures involving fascial closure. A low rate of minor complications was observed in both groups at 1 month [4.4 % (VG) and 2.3 % (CG)], and the level of postoperative pain was similar in the two groups at Day 8 and 1 month. After 1 year, no complications, recurrences or cases of chronic pain had occurred in either group, and Quality-of Life outcomes were similar. Patients rated their procedure as excellent or good in 96 % (VG) and 92 % (CG) of cases. CONCLUSIONS: Ventralight STTM mesh is effective and well tolerated in LVHR, producing very low complication and recurrence rates in the short and medium term. The results are comparable to those achieved with other types of mesh. PMID- 27278221 TI - Pharmacologic Approaches to Electrolyte Abnormalities in Heart Failure. AB - Electrolyte abnormalities are common in heart failure and can arise from a variety of etiologies. Neurohormonal activation from ventricular dysfunction, renal dysfunction, and heart failure medications can perturb electrolyte homeostasis which impact both heart failure-related morbidity and mortality. These include disturbances in serum sodium, chloride, acid-base, and potassium homeostasis. Pharmacological treatments differ for each electrolyte abnormality and vary from older, established treatments like the vaptans or acetazolamide, to experimental or theoretical treatments like hypertonic saline or urea, or to newer, novel agents like the potassium binders: patiromer and zirconium cyclosilicate. Pharmacologic approaches range from limiting electrolyte intake or directly repleting the electrolyte, to blocking or promoting their resorption, and to neurohormonal antagonism. Because of the prevalence and clinical impact of electrolyte abnormalities, understanding both the older and newer therapeutic options is and will continue to be necessity for the management of heart failure. PMID- 27278223 TI - Erratum to: Traumatic brain injury and age at onset of cognitive impairment in older adults. PMID- 27278222 TI - Overt hepatic encephalopathy: development of a novel clinician reported outcome tool and electronic caregiver diary. AB - Clinical management and clinical trials of patients with overt hepatic encephalopathy (OHE) are compromised by lack of standardized and reproducible tools for its clinical diagnosis or for caregiver (CG) identification of OHE manifestations which merit medical evaluation. Using an iterative Delphi method, Steering Committee and international hepatologist panel, the West Haven (WH) scale was modified to develop and operationalize a clinician tool for OHE identification and grading (HE Grading Instrument, HEGITM). Major diagnostic criteria included disorientation to time, place, and person, asterixis, lethargy, and coma. Minimum HEGI requirements for OHE diagnosis included: (1) disorientation, or (2) presence of both lethargy and asterixis, or (3) coma. Inter- and intra-rater HEGI reproducibility were 97 % and 98 %, respectively. When applied to a phase II clinical trial population of 178 patients with 388 OHE episodes, HEGI demonstrated excellent concordance with investigator judgement. Additionally, a multi-stage study was conducted to develop a daily CG e-diary, based on OHE manifestations recognizable by CG including speech difficulties, unusual behavior, forgetfulness, confusion, disorientation and level of consciousness. The e-diary was designed for use on smart phone, laptop or desktop, utilized branching logic and skip patterns, incorporated automatic daily completion reminders and real time alerts to clinical sites to facilitate daily standardized CG input and was found to be user friendly and understandable. The HEGI and e-diary, which were developed using methodology accepted by regulatory authorities, are designed to facilitate the design and interpretation of clinical trials for OHE and improve outcomes for OHE patients in clinical practice. PMID- 27278224 TI - Chemical composition and anti-inflammatory activity of the leaves of Byrsonima verbascifolia. AB - An ethnopharmacological survey indicates that the genus Byrsonima has some medicinal species that are commonly found in the Brazilian Cerrado and has been used as an anti-inflammatory and for gastroduodenal disorders. The aim of this study was to evaluate the anti-inflammatory and antioxidant activity along with qualitative chemical characterization of the methanolic extract of the leaves of Byrsonima verbascifolia (BvME) obtained by exhaustive percolation. The data from the chemical analyses by liquid chromatography-mass spectrometry led to tentative identification of 42 compounds belonging to proanthocyanidins, galloyl quinic acid derivatives, flavonoids, and triterpene glycoside derivatives. BvME contain flavonoids and show an antioxidative activity. The methanolic extract administered intraperitoneally at doses of 50, 100, or 300 mg/kg showed a significant reduction in paw edema and modulated the neutrophil influx in a mouse model. Furthermore, the anti-edematogenic activity of the extract provided in smaller doses (12.5 and 25 mg/kg) was also demonstrated in a mouse paw edema model. The extract inhibited NO production by macrophages induced by lipopolysaccharide. We presume that the anti-inflammatory effects of BvME are due to a combination of compounds present in B. verbascifolia, including catechins (procyanidins), flavonoids, and triterpene glycosides and that these anti inflammatory actions should be mediated, at least partly, through the inhibition of NO production. This study supports and validates the ethnopharmacological uses of B. verbascifolia as an anti-inflammatory. PMID- 27278225 TI - Aqueous extract of pomegranate seed attenuates glucocorticoid-induced bone loss and hypercalciuria in mice: A comparative study with alendronate. AB - The present study was performed in order to examine bone loss and calcium homeostasis in mice with glucocorticoid (GC)-induced osteoporosis (GIOP) following treatment with the aqueous extract of pomegranate seed (AE-PS). In addition, a comparative study with alendronate was performed. Biomarkers in the serum and the urine were measured. The tibias, kidney and duodenum were removed in order to measure the levels of bone calcium, protein expression as well as to perform histomorphological analysis of the bone. GC treatment facilitated the induction of hypercalciuria in the mice, and the AE-PS-treated mice exhibited a greater increase in serum calcium and a decrease in urine calcium. The AE-PS reversed the deleterious effects on the trabecular bone induced by DXM and stimulated bone remodeling, including an increase in bone calcium and alkaline phosphatase-b (ALP-b) and a decrease in a the critical bone resorption markers C terminal telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase-5b (TRAP-5b). Hematoxylin and eosin (H&E) staining revealed the increased disconnections and separation between the growth plate and the trabecular bone network as well as the reduction in the trabecular bone mass of the primary and secondary spongiosa throughout the proximal metaphysis of the tibia in the DXM group. Moreover, the decreased protein expression of transient receptor potential vanilloid (TRPV)5, TRPV6 and calbindin-D9k (CaBP-9k) was reversed by the AE-PS or alendronate supplementation in the kidneys and the duodenum as well as plasma membrane Ca2+-ATPase1 (PMCA1) expression in the kidneys of mice with GIOP. There was no marked difference in pharmacological effectiveness between alendronate and the AE-PS. Taken together, these findings suggest that the AE-PS may be an alternative therapy suitable for use in the management of secondary osteoporosis. PMID- 27278226 TI - Clinical significance of anterior mitral leaflet fibrillation in patients with nonvalvular atrial fibrillation: comparison with blood flow and wall motion of the left atrial appendage. AB - BACKGROUND AND PURPOSE: Diastolic fibrillation of the anterior mitral leaflet (AML) is seen in patients with atrial fibrillation (AF). However, its clinical significance has been unclear. On the other hand, reduced blood flow velocity in the left atrial appendage (LAA) may be associated with LA thrombus formation. In this study, we investigate the relationship between the flow velocity and the wall motion velocity of the LAA and diastolic fibrillation of the AML in patients with nonvalvular AF. METHODS: We performed transthoracic echocardiography (TTE) in 45 consecutive patients with chronic nonvalvular AF. The LAA flow velocity was measured by pulsed Doppler echocardiography with the sample volume positioned at the center of the LAA. The LAA wall motion velocity was measured by pulsed Doppler tissue imaging (DTI) with the sample volume at the medial wall of the LAA. The AML fibrillation velocity was measured by pulsed DTI with the sample volume at the AML tip. RESULTS: The AML fibrillation velocity could be measured in 44 patients (97.8%), and the LAA flow and wall motion velocities were measurable in 35 (77.8%) and 42 (93.3%) patients, respectively. The AML fibrillation velocity had a range from 4 to 21 cm/s and showed significant positive correlation with the LAA flow velocity (r = 0.82, P < 0.001) and the wall motion velocity (r = 0.80, P < 0.001) of the LAA. An AML fibrillation velocity of <=7 cm/s predicted patients having a tendency to LA thrombus formation (LAA flow velocity <=20 cm/s) with high sensitivity (87.5%) and specificity (88.9%). CONCLUSION: The AML fibrillation velocity seems to be a viable substitute for the LAA flow velocity in the detection of flow stagnation in the LA. PMID- 27278227 TI - Right ventricular diastolic dysfunction in patients with left ventricular hypertrophy: analysis of right ventricular myocardial relaxation using two dimensional speckle tracking imaging. AB - BACKGROUND: Although several previous studies have suggested the presence of right ventricular (RV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM) and those with hypertensive left ventricular hypertrophy (HT LVH), the mechanisms are still unclear. This study aimed to clarify the relationship between the RV global diastolic dysfunction in these patients and the regional myocardial diastolic function, including synchronicity of the interventricular septum and RV free wall. METHODS: In 20 age-matched patients with HT-LVH, 20 patients with HCM and 22 control subjects without pulmonary hypertension, RV isovolumic relaxation time (IRTR) was measured using continuous wave Doppler echocardiography. The early diastolic peak strain rate (E SR) and time from QRS to E SR (T-E SR) were measured in the apical, mid-ventricular and basal segments of the interventricular septum and RV free wall using two dimensional speckle tracking imaging (2DST). RESULTS: IRTR was more prolonged both in HT-LVH and in HCM than in the controls. The averaged septal E SR was reduced both in HT-LVH and in HCM (P < 0.0001, respectively), but the averaged RV free wall E SR was decreased only in HCM (P = 0.0007). E SR averaged for six septal and RV free wall segments was correlated with IRTR (r = -0.46, P = 0.0001). Neither intergroup difference nor correlation with IRTR was observed in a coefficient of variation of T-E SR for the six segments. CONCLUSIONS: RV global diastolic function is impaired in patients with HT-LVH and HCM due to relaxation abnormalities, not an asynchrony, of the myocardium surrounding the RV cavity. The detection of RV free wall relaxation abnormality using 2DST may be useful to differentiate HCM from HT-LVH. PMID- 27278228 TI - Inverted Takotsubo cardiomyopathy masking acute myocardial infarction. AB - We report a case of inverted Takotsubo cardiomyopathy masking acute myocardial infarction. In this case, echocardiography on admission showed left ventricular mid and basal akinesis and apical hyperkinesis compatible with an inverted Takotsubo contractile pattern. In the subacute phase, however, he was suspected of having acute myocardial infarction by serial changes of cardiac enzymes. After 8 days of admission, echocardiography showed normalization of the left ventricular contraction, except the inferior wall which was compatible with inferior myocardial infarction. Subsequent myocardial scintigraphy confirmed the diagnosis. It is important to recognize that inverted Takotsubo cardiomyopathy may mask acute myocardial infarction when they occur simultaneously. PMID- 27278229 TI - Tornado-like appearance of spontaneous echo contrast assessed by real-time 3D transesophageal echocardiography. AB - We report a case showing that real-time 3D transesophageal echocardiography provides unique information about the dynamic nature of spontaneous echo contrast (SEC) in 3D space and has the potential to provide better understanding of SEC. PMID- 27278230 TI - Large atrial septal defect visualized by real-time three-dimensional echocardiography. PMID- 27278232 TI - Association of alcohol consumption with the onset of natural menopause: a systematic review and meta-analysis. AB - BACKGROUND: Early onset of menopause is associated with long-term health risks, including cardiovascular disease and premature death. Although alcohol intake has been suggested to affect the age at which natural menopause occurs, results from observational studies are not consistent. OBJECTIVE AND RATIONALE: In the view of the differing risks to the health of early menopause and the increasing trends in alcohol consumption in women, in this systematic review, we aimed to quantify the association between all levels of alcohol consumption and menopause onset. SEARCH METHODS: Six electronic databases (Medline, Embase, Cochrane, PubMed, Google Scholar and Web of Science) were systematically searched until 4 November 2015 to identify relevant studies assessing the association between alcohol consumption and onset of menopause. Two independent reviewers screened the titles and abstracts of all initially identified studies according to the selection criteria. Studies were sought if they (i) were observational cross-sectional, prospective and interventional studies, (ii) had reported on natural onset of menopause, (iii) had reported on alcohol consumption, (iv) had assessed the association between alcohol consumption and menopause onset, (v) were conducted in humans and (vi) were not conducted in patients with cancer. Data were extracted by two independent reviewers using a predesigned data-collection form. The primary exposure variable was the presence of active alcohol drinking at baseline compared with a reference group of non-drinkers. Pooled relative risks (RRs) were calculated. OUTCOMES: Of the 1193 references (all in English language) reviewed for eligibility, 22 articles based on 20 unique studies were included in the final analysis. A total of 41 339 and 63 868 non-overlapping women were included in the meta-analysis of cross-sectional and observational cohort studies, respectively. In cross-sectional studies, the pooled RR for earlier onset of menopause was 0.86 (95% confidence interval (CI): 0.78-0.96) between drinkers versus non-drinkers. Analysis of the levels of alcohol consumed showed that low and moderate alcohol consumption (more than one drink per week (RR = 0.60; 95% CI: 0.49-0.75) and three or fewer drinks per week (RR = 0.75; 95% CI: 0.60-0.94)) were associated with later menopause onset, compared to non-drinkers. In prospective studies, RR for earlier menopause onset was 0.95 (95% CI: 0.91 0.98) when comparing women who reported drinking alcohol versus women who did not. Analysis of the dose of alcohol consumed showed that low-to-moderate alcohol intake (0-8 g/day (RR = 0.95; 95% CI: 0.93-0.98), and 16 g/day (RR = 0.89, 95%CI: 0.86-0.92)) was associated with later menopause onset, compared to non-drinking. WIDER IMPLICATIONS: The findings of this review indicate that alcohol consumption, particularly low and moderate alcohol intake, might be associated with later onset of menopause although the magnitude of the association is low. Further studies are needed to corroborate these findings, clarify the level of alcohol intake at which menopause is delayed and identify the potential mechanisms behind this association. PMID- 27278233 TI - Discounting the duration of bolus exposure in impedance testing underestimates acid reflux. AB - BACKGROUND: Combined impedance-pH testing (MII) allows for detection of reflux episodes regardless of pH. However impedance-based diagnosis of reflux may not routinely account for duration of the reflux episode. We hypothesize that impedance testing may be less sensitive than pH-testing in detecting acid reflux off therapy as a result of discounting duration of exposure. METHODS: Baseline characteristics and reflux parameters of MII studies performed off-anti-secretory medications were analyzed. Studies on acid suppressive medication and those with recording times less than 20 h or low baseline impedance were excluded. RESULTS: A total of 73 consecutive MII studies were analyzed of which 31 MII studies had elevated acid exposure while 16 were abnormal by impedance criteria. MII testing off-therapy was more likely to be abnormal by pH criteria (percent time pH < 4) than impedance criteria (total reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH < 4) identified more studies as abnormal than MII-detected acid reflux episodes [42 vs 34 % (p < 0.01)]. Mean acid clearance time (pH-detected) was significantly longer than median bolus clearance time (impedance-detected) in the total [98.7 s vs 12.6 s (p < 0.01)], upright [58.6 s vs 13.1 s (p < 0.01)], and recumbent positions [136.7 s vs 14.2 s (p < 0.01)] with the greatest difference seen in the recumbent position. The mean ratio of mean acid clearance time (pH-detected) and the median bolus clearance time (impedance-detected) was significantly higher in the recumbent position compared to the upright position [11. vs 5.3 (p = 0.01)]. CONCLUSION: Ambulatory impedance testing underestimates acid reflux compared to esophageal acid exposure by discounting the prolonged period of mucosal contact with each acid reflux episode, particularly in the recumbent position. PMID- 27278234 TI - Comparison of (+)- and (-)-Naloxone on the Acute Psychomotor-Stimulating Effects of Heroin, 6-Acetylmorphine, and Morphine in Mice. AB - Toll-like receptor 4 (TLR4) signaling is implied in opioid reinforcement, reward, and withdrawal. Here, we explored whether TLR4 signaling is involved in the acute psychomotor-stimulating effects of heroin, 6-acetylmorphine (6-AM), and morphine as well as whether there are differences between the three opioids regarding TLR4 signaling. To address this, we examined how pretreatment with (+)-naloxone, a TLR4 active but opioid receptor (OR) inactive antagonist, affected the acute increase in locomotor activity induced by heroin, 6-AM, or morphine in mice. We also assessed the effect of pretreatment with (-)-naloxone, a TLR4 and OR active antagonist, as well as the pharmacokinetic profiles of (+) and (-)-naloxone in the blood and brain. We found that (-)-naloxone reduced acute opioid-induced locomotor activity in a dose-dependent manner. By contrast, (+)-naloxone, administered in doses assumed to antagonize TLR4 but not ORs, did not affect acute locomotor activity induced by heroin, 6-AM, or morphine. Both naloxone isomers exhibited similar concentration versus time profiles in the blood and brain, but the brain concentrations of (-)-naloxone reached higher levels than those of (+)-naloxone. However, the discrepancies in their pharmacokinetic properties did not explain the marked difference between the two isomers' ability to affect opioid-induced locomotor activity. Our results underpin the importance of OR activation and do not indicate an apparent role of TLR4 signaling in acute opioid-induced psychomotor stimulation in mice. Furthermore, there were no marked differences between heroin, 6-AM, and morphine regarding involvement of OR or TLR4 signaling. PMID- 27278231 TI - Gamete activation: basic knowledge and clinical applications. AB - BACKGROUND: The first clues to the process of gamete activation date back to nearly 60 years ago. The mutual activation of gametes is a crucial event during fertilization. In the testis and ovaries, spermatozoa and oocytes are in a state of meiotic and metabolic quiescence and require reciprocal signals in order to undergo functional changes that lead to competence for fertilization. First, the oocyte activates sperm by triggering motility, chemoattraction, binding and the acrosome reaction, culminating with the fusion of the two plasma membranes. At the end of this cascade of events, collectively known as sperm capacitation, sperm-induced oocyte activation occurs, generating electrical, morphological and metabolic modifications in the oocyte. OBJECTIVE AND RATIONALE: The aim of this review is to provide the current state of knowledge regarding the entire process of gamete activation in selected specific animal models that have contributed to our understanding of fertilization in mammals, including humans. Here we describe in detail the reciprocal induction of the two activation processes, the molecules involved and the mechanisms of cell interaction and signal transduction that ultimately result in successful embryo development and creation of a new individual. SEARCH METHODS: We carried out a literature survey with no restrictions on publication date (from the early 1950s to March 2016) using PubMed/Medline, Google Scholar and Web of Knowledge by utilizing common keywords applied in the field of fertilization and embryo development. We also screened the complete list of references published in the most recent research articles and relevant reviews published in English (both animal and human studies) on the topics investigated. OUTCOMES: Literature on the principal animal models demonstrates that gamete activation is a pre-requisite for successful fertilization, and is a process common to all species studied to date. We provide a detailed description of the dramatic changes in gamete morphology and behavior, the regulatory molecules triggering gamete activation and the intracellular ions and second messengers involved in active metabolic pathways in different species. Recent scientific advances suggest that artificial gamete activation may represent a novel technique to improve human IVF outcomes, but this approach requires caution. WIDER IMPLICATIONS: Although controversial, manipulation of gamete activation represents a promising tool for ameliorating the fertilization rate in assisted reproductive technologies. A better knowledge of mechanisms that transform the quiescent oocyte into a pluripotent cell may also provide new insights for the clinical use of stem cells. PMID- 27278235 TI - The Role of Presenilin-1 in the Excitotoxicity of Ethanol Withdrawal. AB - Presenilin-1 (PS1) is a core component of gamma-secretase that is involved in neurodegeneration. We have previously shown that PS1 interacts with a mitogen activated protein kinase [(MAPK) jun-NH2-terminal-kinase], and another MAPK (p38) is activated by ethanol withdrawal (EW), abrupt termination from chronic ethanol exposure. EW is excitotoxic in nature, induces glutamate upregulation, and provokes neuronal damage. Here, we explored a potential mechanistic pathway involving glutamate, p38 (p38alpha isozyme), and PS1 that may mediate EW-induced excitotoxic stress. We used the prefrontal cortex of male rats withdrawn from a chronic ethanol diet. Additionally, we used ethanol-withdrawn HT22 cells (mouse hippocampal) treated with the inhibitor of glutamate receptors [dizocilpine (MK 801)], p38alpha (SB203580; 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H imidazol-5-yl]pyridine), or gamma-secretase [N-[N- (3,5-difluorophenacetyl)-l alanyl]-S-phenylglycine t-butyl ester (DAPT)] during EW. Separately, ethanol-free HT22 cells were exposed to glutamate with or without SB203580 or DAPT. Protein levels, mRNA levels, and cell viability were assessed using immunoblotting, qualitative polymerase chain reaction, and calcein assay, respectively. The prefrontal cortex of ethanol-withdrawn rats or HT22 cells showed an increase in PS1 and p38alpha, which was attenuated by MK-801 and SB203580, but mimicked by glutamate treatment to ethanol-free HT22 cells. DAPT attenuated the toxic effect of EW or glutamate on HT22 cells. These results suggest that PS1 expression is triggered by glutamate through p38alpha, contributing to the excitotoxic stimulus of EW. PMID- 27278237 TI - Concomitant Scrofuloderma and Tuberculous Osteomyelitis of Mandible. PMID- 27278236 TI - Features of the Phosphatidylinositol Cycle and its Role in Signal Transduction. AB - The phosphatidylinositol cycle (PI-cycle) has a central role in cell signaling. It is the major pathway for the synthesis of phosphatidylinositol and its phosphorylated forms. In addition, some lipid intermediates of the PI-cycle, including diacylglycerol and phosphatidic acid, are also important lipid signaling agents. The PI-cycle has some features that are important for the understanding of its role in the cell. As a cycle, the intermediates will be regenerated. The PI-cycle requires a large amount of metabolic energy. There are different steps of the cycle that occur in two different membranes, the plasma membrane and the endoplasmic reticulum. In order to complete the PI-cycle lipid must be transferred between the two membranes. The role of the Nir proteins in the process has recently been elucidated. The lipid intermediates of the PI-cycle are normally highly enriched with 1-stearoyl-2-arachidonoyl molecular species in mammals. This enrichment will be retained as long as the intermediates are segregated from other lipids of the cell. However, there is a significant fraction (>15 %) of lipids in the PI-cycle of normal cells that have other acyl chains. Phosphatidylinositol largely devoid of arachidonoyl chains are found in cancer cells. Phosphatidylinositol species with less unsaturation will not be as readily converted to phosphatidylinositol-3,4,5-trisphosphate, the lipid required for the activation of Akt with resulting effects on cell proliferation. Thus, the cyclical nature of the PI-cycle, its dependence on acyl chain composition and its requirement for lipid transfer between two membranes, explain many of the biological properties of this cycle. PMID- 27278238 TI - Recent Advances in Celiac Disease. AB - Recent diagnostic advances have demonstrated that celiac disease is relatively common although most patients have less florid symptoms than previously recognised. The mucosal lesion of this autoimmune disorder depends on both adaptive and innate immune responses. The characteristic antibodies to tissue transglutaminase-2 (tTG-2) and deamidated gliadin peptides may be produced in persons possessing the relevant HLA-DQ genotypes if intact gliadin peptides can penetrate the epithelial barrier to reach antigen presenting cells. Progression from celiac autoimmunity to overt disease may depend on innate immune mechanisms, not HLA-restricted, where IL-15 is generated within the epithelial compartment. A specific innate immune response previously thought restricted to invertebrates, the encapsulation reaction, may contribute to mucosal volume expansion through recruitment of syndecan-expressing leukocytes and stimulated matrix production. It is notable that tissue transglutaminase is critical in this reaction in insects, and that the very few insects that can predate wheat, possess specific salivary or intestinal enzymes that degrade gluten. Animal models in HLA-DQ transgenic mice suggest that the microbial flora of the intestine may play a role in host responses and modulate the evolution of the disease. This suggests that therapeutic modulation of the microbiome may contribute to management of celiac disease. In developing world countries, there is a potential difficulty in histological diagnosis because of the widespread incidence of environmental enteropathy amongst apparently healthy children. Thus, recognition of local patterns of enteropathy will be important for histopathologists, and high titre tTG-2 autoantibody titres may hold considerable diagnostic significance. PMID- 27278239 TI - Ascites in Children. AB - Ascites is an accumulation of serous fluid within the peritoneal cavity. It is the most common complication of liver cirrhosis. In children, hepatic, renal and cardiac disorders are the most common causes. Portal hypertension and sodium and fluid retention are key factors in the pathophysiology of ascites. Peripheral arterial vasodilatation hypothesis is the most accepted mechanism for inappropriate sodium retention and formation of ascites. Diagnostic paracentesis is indicated in children with newly diagnosed ascites and in children with suspected complications of ascites. Ascitic fluid is evaluated for cell count, protein level, and culture. The serum-ascites albumin gradient (SAAG) is the best single test for classifying ascites into portal hypertensive (SAAG >1.1 g/dl) and non-portal hypertensive (SAAG <1.1 g/dl). A neutrophil count >=250 cells/mm3 is highly suggestive of bacterial peritonitis. The treatment of ascites due to non liver disease depends on the underlying condition. In liver disease, diuretics as monotherapy or dual therapy and salt restriction form the mainstay of treatment in children with mild to moderate ascites. Fluid restriction is helpful in children with hyponatremia. In non-responsive ascites or in children with large ascites, large volume paracentesis (LVP) with albumin infusion should be performed. In children with refractory ascites, LVP with albumin administration, transjugular intrahepatic porto-systemic shunt (TIPS), peritoneo-venous shunting and liver transplantation are other therapeutic modalities that need to be considered. PMID- 27278240 TI - Ultra-low-dose CT Imaging of the Thorax: Decreasing the Radiation Dose by One Order of Magnitude. AB - Computed tomography (CT) is an indispensable tool for imaging of the thorax and there is virtually no alternative without associated radiation burden. The authors demonstrate ultra-low-dose CT of the thorax in three interesting cases. In an 18-y-old girl with rheumatoid arthritis, CT of the thorax identified alveolitis in the posterior costophrenic angles (radiation dose = 0.2 mSv). Its resolution was demonstrated on a follow-up scan (4.2 mSv) performed elsewhere. In an 11-y-old girl, CT (0.1 mSv) showed changes of the right collar bone consistent with chronic recurrent multifocal osteomyelitis. CT (0.1 mSv) of a 9-y-old girl with mucopolysaccharidosis revealed altogether three hamartomas, peribronchial infiltrate, and spine deformity. In some indications, the radiation dose from CT of the thorax can approach that of several plain radiographs. This may help the pediatrician in deciding whether "gentle" ultra-low-dose CT instead of observation or follow-up radiographs will alleviate the uncertainty of the diagnosis with little harm to the child. PMID- 27278242 TI - Synthesis of Discrete Alkyl-Silica Hybrid Nanowires and Their Assembly into Nanostructured Superhydrophobic Membranes. AB - We report the synthesis of highly flexible and mechanically robust hybrid silica nanowires (NWs) which can be used as novel building blocks to construct superhydrophobic functional materials with three-dimensional macroporous networks. The hybrid silica NWs, with an average diameter of 80 nm and tunable length of up to 12 MUm, are prepared by anisotropic deposition of the hydrolyzed tetraethylorthosilicate in water/n-pentanol emulsions. A mechanistic investigation reveals that the trimethoxy(octadecyl)silane introduced to the water-oil interface in the synthesis plays key roles in stabilizing the water droplets to sub-100 nm and also growing a layer of octadecyl groups on the NW surface. This work opens a solution-based route for the one-pot preparation of monodisperse, hydrophobic silica NWs and represents an important step toward the bottom-up construction of 3D superhydrophobic materials and macroporous membranes. PMID- 27278241 TI - Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles. AB - BACKGROUND: It is difficult to discriminate healthy subjects and patients with Parkinson disease (PD) or Parkinson disease dementia (PDD) by assaying plasma alpha-synuclein because the concentrations of circulating alpha-synuclein in the blood are almost the same as the low-detection limit using current immunoassays, such as enzyme-linked immunosorbent assay. In this work, an ultra-sensitive immunoassay utilizing immunomagnetic reduction (IMR) is developed. The reagent for IMR consists of magnetic nanoparticles functionalized with antibodies against alpha-synuclein and dispersed in pH-7.2 phosphate-buffered saline. A high-Tc superconducting-quantum-interference-device (SQUID) alternative-current magnetosusceptometer is used to measure the IMR signal of the reagent due to the association between magnetic nanoparticles and alpha-synuclein molecules. RESULTS: According to the experimental alpha-synuclein concentration dependent IMR signal, the low-detection limit is 0.3 fg/ml and the dynamic range is 310 pg/ml. The preliminary results show the plasma alpha-synuclein for PD patients distributes from 6 to 30 fg/ml. For PDD patients, the concentration of plasma alpha-synuclein varies from 0.1 to 100 pg/ml. Whereas the concentration of plasma alpha-synuclein for healthy subjects is significantly lower than that of PD patients. CONCLUSIONS: The ultra-sensitive IMR by utilizing antibody functionalized magnetic nanoparticles and high-Tc SQUID magnetometer is promising as a method to assay plasma alpha-synuclein, which is a potential biomarker for discriminating patients with PD or PDD. PMID- 27278243 TI - Osteoarthritic changes rather than age predict outcome following arthroscopic treatment of femoroacetabular impingement in middle-aged patients. AB - BACKGROUND: Our purpose was to evaluate outcome following arthroscopic treatment of femoroacetabular impingement (FAI) in middle-aged patients and to define risk factors for conversion to total hip arthroplasty (THA). METHODS: This was a retrospective case series of 79 consecutive patients (40 to 65 years) undergoing arthroscopic treatment of FAI (follow-up >=12 months). Outcome at follow-up was assessed using Hip outcome score (HOS). Alpha angle, Kellgren Lawrence grade (K-L grade), joint space width (JS), lateral center edge (LCE) angle, caput-collum diaphysis (CCD) angle and acetabular index (AI) were analysed retrospectively. THA group and Non-THA group were compared. RESULTS: Seventy-nine patients (mean age 48.6 years, mean follow-up 32 months) were included. 18 patients (22.8 %) were converted to THA. Mean HOS score in the Non-THA group at time point of follow-up was 80.2. Non-THA group and THA group showed no significant differences for mean age (48.2 years vs. 49.9 years, p = 0.278), alpha angel (p = 0.541), LCE (p = 0.294), CCD (p = 0.101) and AI (p = 0.661) in contrast to differences for JS (p = <0.001) and K-L grade (p = <0.001). Risk of conversion to THA was higher for patients with K-L grade 3 (p = 0.003) or joint space less or equal 2 mm (p = 0.001). CONCLUSIONS: One fifth of the middle-aged patients required early conversion to THA. Advanced JS narrowing and K-L grade rather than age alone can be considered as risk factor for conversion to THA. PMID- 27278245 TI - Potential diagnostic value of lncRNA SPRY4-IT1 in hepatocellular carcinoma. AB - The manifestation of hepatocellular carcinoma (HCC) involves a multi-factor, multi-step and complex process. Due to the lack of early prediction indices, numerous patients are diagnosed in their late stage. Recently, research in the field of non-coding RNAs (ncRNAs) has changed the original idea that ncRNA genes are just noise. Cumulative evidence shows that long non-coding RNAs (lncRNAs) among ncRNAs play an increasingly important role in epigenetics, pre transcription and post-transcription. In the present study, we focused on the expression pattern of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and its clinical significance in HCC diagnostics. We analyzed the expression, its association with clinical characteristics and the diagnostic value of SPRY4-IT1 using HCC tissues, cell lines and plasma. The levels of SPRY4-IT1 were upregulated in HCC and were associated with tumor differentiation (r=0.249, p=0.039), tumor size (r=0.258, p=0.024) and tumor-node-metastasis (TNM) stage (r=0.287, p=0.015). Meanwhile, the sensitive of SPRY4-IT1 was 87.3% in differentiating HCC patients from controls. Our data suggest that SPRY4-IT1 plays a critical role in HCC tumorigenesis and may be considered as a potential diagnostic indicator in HCC. PMID- 27278247 TI - Corrigendum. PMID- 27278248 TI - Cuts in health prevention budgets will hit the NHS, says NHS England chief. PMID- 27278244 TI - Accuracy of novel diagnostic biomarkers for hepatocellular carcinoma: An update for clinicians (Review). AB - Hepatocellular carcinoma (HCC) is the most common liver malignancy and a leading cause of cancer-related mortality worldwide. Accurate detection and differential diagnosis of early HCC can significantly improve patient survival. Currently, detection of HCC in clinical practice is performed by diagnostic imaging techniques and determination of serum biomarkers, most notably alpha-fetoprotein (AFP), fucosylated AFP and des-gamma-carboxyprothrombin. However, these methods display limitations in sensitivity and specificity, especially with respect to early stages of HCC. Recently, high-throughput technologies have elucidated many new pathways involved in hepatocarcinogenesis and have led to the discovery of a plethora of novel, non-invasive serum biomarkers. In particular, the combination of AFP with these new candidate molecules has yielded promising results. In this review, we aimed at recapitulating the most recent (2013-2015) developments in HCC biomarker research. We compared promising novel diagnostic serum protein biomarkers, such as annexin A2, the soluble form of the receptor tyrosine kinase Axl and thioredoxin, as well as their combinations with AFP. High diagnostic performance (area under the curve >0.75) as shown by threshold-independent receiver operating characteristic curve analysis was a prerequisite for inclusion in this review. In addition, we discuss the role and potential of microRNAs in HCC diagnosis and associated methodological challenges. PMID- 27278246 TI - Endophenotype Network Models: Common Core of Complex Diseases. AB - Historically, human diseases have been differentiated and categorized based on the organ system in which they primarily manifest. Recently, an alternative view is emerging that emphasizes that different diseases often have common underlying mechanisms and shared intermediate pathophenotypes, or endo(pheno)types. Within this framework, a specific disease's expression is a consequence of the interplay between the relevant endophenotypes and their local, organ-based environment. Important examples of such endophenotypes are inflammation, fibrosis, and thrombosis and their essential roles in many developing diseases. In this study, we construct endophenotype network models and explore their relation to different diseases in general and to cardiovascular diseases in particular. We identify the local neighborhoods (module) within the interconnected map of molecular components, i.e., the subnetworks of the human interactome that represent the inflammasome, thrombosome, and fibrosome. We find that these neighborhoods are highly overlapping and significantly enriched with disease-associated genes. In particular they are also enriched with differentially expressed genes linked to cardiovascular disease (risk). Finally, using proteomic data, we explore how macrophage activation contributes to our understanding of inflammatory processes and responses. The results of our analysis show that inflammatory responses initiate from within the cross-talk of the three identified endophenotypic modules. PMID- 27278249 TI - Oridonin enhances the anticancer activity of NVP-BEZ235 against neuroblastoma cells in vitro and in vivo through autophagy. AB - The aberrant activation of PI3K/Akt/mTOR signaling pathway plays an important role in the oncogenesis, prognosis and chemotherapy resistance of neuroblastoma. However, NVP-BEZ235, a potent dual PI3K and mTOR inhibitor have not shown beneficial effects on neuroblastoma especially in terms of apoptosis induction as a single agent. We therefore attempted to explore an effective combination regimen to enhance the anticancer activity of NVP-BEZ235. Interestingly, we found that oridonin, a natural biologically active compound extracted from the Chinese medicinal herb Rabdosia rubescens, combined with NVP-BEZ235 markedly induced apoptosis of neuroblastoma cells. Notably, the synergistic activation of the apoptotic pathway was accompanied with enhanced autophagy as evidenced by significant decreased p62 expression as well as upregulated conversion of LC3-II. Suppression of the Beclin-1, a core component of the autophagy machinery, by means of shRNA resulted in diminished synergistic antitumor effect. Furthermore, the co-treatment with oridonin and NVP-BEZ235 was also much more effective than either agent alone in inhibiting the growth of neuroblastoma xenografts and in inducing tumor cells apoptosis. Taken together, our results suggest that the combination of NVP-BEZ235 and oridonin is a novel and potential strategy for neuroblastoma therapy. PMID- 27278251 TI - Estuarization increases functional diversity of demersal fish assemblages in tropical coastal ecosystems. AB - This study assessed the influence of the seasonal fluctuation of abiotic conditions (wet v. dry season) on the functional diversity (FD) of tropical coastal fish assemblages. Sampling was carried out in three regions of north-east Brazil with contrasting coastlines (influenced by reef, lagoon and estuary). In each region, fishes were sampled from three depth strata (10, 20 and 30 m) and FD was estimated using an index based on key phenotypic and behavioural characteristics. All three regions had higher FD in the wet season at shallower depths, indicating the coexistence of species with low functional redundancy in sites subject to seasonal flushing of fresh water. Deeper sites had lower FD than shallower sites, although this difference was less pronounced for region 3, which is strongly affected by its proximity to the Sao Francisco estuary. The results broadly support the hypothesis that alterations in abiotic conditions in the wet season allow estuarine-adapted fishes with a different suite of functional traits to invade shallow coastal regions. PMID- 27278250 TI - Mentalization-based treatment for psychotic disorder: protocol of a randomized controlled trial. AB - BACKGROUND: Many patients with a non-affective psychotic disorder suffer from impairments in social functioning and social cognition. To target these impairments, mentalization-based treatment for psychotic disorder, a psychodynamic treatment rooted in attachment theory, has been developed. It is expected to improve social cognition, and thereby to improve social functioning. The treatment is further expected to increase quality of life and the awareness of having a mental disorder, and to reduce substance abuse, social stress reactivity, positive symptoms, negative, anxious and depressive symptoms. METHODS/DESIGN: The study is a rater-blinded randomized controlled trial. Patients are offered 18 months of therapy and are randomly allocated to mentalization-based treatment for psychotic disorders or treatment as usual. Patients are recruited from outpatient departments of the Rivierduinen mental health institute, the Netherlands, and are aged 18 to 55 years and have been diagnosed with a non-affective psychotic disorder. Social functioning, the primary outcome variable, is measured with the social functioning scale. The administration of all tests and questionnaires takes approximately 22 hours. Mentalization-based treatment for psychotic disorders adds a total of 60 hours of group therapy and 15 hours of individual therapy to treatment as usual. No known health risks are involved in the study, though it is known that group dynamics can have adverse effects on a psychiatric disorder. DISCUSSION: If Mentalization based treatment for psychotic disorders proves to be effective, it could be a useful addition to treatment. TRIAL REGISTRATION: Dutch Trial Register. NTR4747 . Trial registration date 08-19-2014. PMID- 27278253 TI - Evaluation of VITEK matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of anaerobes. AB - Rapid and adequate identification of anaerobic bacterial species still presents a challenge for most diagnostic laboratories, hindering the selection of appropriate therapy. In this study, the identification capacity of 16S rRNA sequence analysis, VITEK 2 (BioMerieux, Lyon, France) compact analysis and VITEK MS-mediated identification for anaerobic bacterial species was compared. Eighty five anaerobic bacterial isolates from 11 provinces in China belonging to 14 genera were identified by these three methods. Differences in identification between these three methods were compared. Consistent identification results were obtained for 54 (54/85, 63.5%) isolates by all three methods, the most discordant results being concentrated in Clostridium XI (n = 8) and Bacteroides fragilis (n = 9) clusters. Using the VITEK MS system, 74 (74/90, 82.2%) isolates were identified as single species consistent with 16S rRNA sequence analysis, which was significantly better than the results obtained with VITEK 2 Compact (P < 0.01). Misidentifications by the Vitek 2 Compact and Vitek MS systems were mainly observed in the Clostridium XI (n = 8)and B. fragilis clusters (n = 9). VITEK MS identified anaerobic bacteria even after they had been exposed to oxygen for a week. Identification by the Vitek MS system was more consistent with 16S rRNA sequence analysis than identification by Vitek 2 Compact. Continuous expansion of the VITEK MS database with rare described anaerobic species is warranted to improve both the efficiency and accuracy of VITEK MS identification in routine diagnostic microbiology. PMID- 27278252 TI - Tuberin regulates reactive oxygen species in renal proximal cells, kidney from rodents, and kidney from patients with tuberous sclerosis complex. AB - Reactive oxygen species (ROS) are an important endogenous source of DNA damage and oxidative stress in all cell types. Deficiency in tuberin resulted in increased oxidative DNA damage in renal cells. In this study, the role of tuberin in the regulating of ROS and NADPH oxidases was investigated. Formation of ROS and activity of NADPH oxidases were significantly higher in mouse embryonic fibroblasts and in primary culture of rat renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells. In addition, expression of NADPH oxidase (Nox)1, Nox2, and Nox4 (Nox isoforms) was higher in mouse embryonic fibroblasts and renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells. Furthermore, activity levels of NADPH oxidases and protein expression of all Nox isoforms were higher in the renal cortex of rat deficient in tuberin. However, treatment of tuberin-deficient cells with rapamycin showed significant decrease in protein expression of all Nox. Significant increase in protein kinase C betaII expression was detected in tuberin-deficient cells, whereas inhibition of protein kinase C betaII by bisindolylmaleimide I resulted in decreased protein expression of all Nox isoforms. In addition, treatment of mice deficient in tuberin with rapamycin resulted in significant decrease in all Nox protein expression. Moreover, protein and mRNA expression of all Nox were highly expressed in tumor kidney tissue of patients with tuberous sclerosis complex compared to control kidney tissue of normal subjects. These data provide the first evidence that tuberin plays a novel role in regulating ROS generation, NADPH oxidase activity, and Nox expression that may potentially be involved in development of kidney tumor in patients with tuberous sclerosis complex. PMID- 27278255 TI - Measuring individual differences in responses to date-rape vignettes using latent variable models. AB - Vignette methodology can be a flexible and powerful way to examine individual differences in response to dangerous real-life scenarios. However, most studies underutilize the usefulness of such methodology by analyzing only one outcome, which limits the ability to track event-related changes (e.g., vacillation in risk perception). The current study was designed to illustrate the dynamic influence of risk perception on exit point from a date-rape vignette. Our primary goal was to provide an illustrative example of how to use latent variable models for vignette methodology, including latent growth curve modeling with piecewise slopes, as well as latent variable measurement models. Through the combination of a step-by-step exposition in this text and corresponding model syntax available electronically, we detail an alternative statistical "blueprint" to enhance future violence research efforts using vignette methodology. Aggr. Behav. 43:60 73, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27278254 TI - Myeloid cell leukaemia 1 has a vital role in retinoic acid-mediated protection of Toll-like receptor 9-stimulated B cells from spontaneous and DNA damage-induced apoptosis. AB - Vitamin A is an essential anti-infective agent with pleiotropic effects on cells of the immune system. The goal of the present study was to unravel the impact of the vitamin A metabolite retinoic acid (RA) on B-cell survival related both to normal B-cell homeostasis and to the detrimental effects imposed by DNA-damaging agents. By combining RA with Toll-like receptor 9 (TLR9) ligands, we show that RA prevents spontaneous, irradiation- and doxorubicin-induced apoptosis of human B cells in an RA receptor-dependent manner. RA-mediated survival involved up regulation of the anti-apoptotic protein myeloid cell leukemia 1 (MCL1) at the transcriptional level, and knock down of MCL1 by small interfering RNA partially reversed the effects of RA. To ensure that the combination of TLR9-ligands and RA would not promote the survival of malignant B cells, the combined effects of stimulation with RA and TLR9 ligands was assessed on cells from patients with B cell malignancies. In contrast to the effects on normal B cells, the combination of TLR9 stimulation and RA neither enhanced the MCL1 levels nor inhibited the death of malignant B cells challenged by DNA-damaging agents. Taken together, the present results reveal a vital role of MCL1 in RA-mediated survival of normal B cells. Moreover, the findings suggest that RA in combination with TLR9 ligands might be useful adjuvants in the treatment of B-cell malignancies by selectively protecting normal and not malignant B cells from DNA-damage-induced cell death. PMID- 27278256 TI - Differences in strength and speed demands between 4v4 and 8v8 small-sided football games. AB - The aims of this study were (i) to characterise the acceleration demands of two different formats of small-sided game (SSG), i.e., 4v4 + goalkeepers (4v4 + GK) and 8v8 + goalkeepers (8v8 + GK); (ii) to analyse the correlation between performance in power-based tests and acceleration-based physical loading during the two different SSG formats and (iii) to analyse the neuromuscular-induced fatigue. Eighteen adult male footballers participated in the study (20.7 +/- 1.0 years, 178 +/- 5 cm and 71.4 +/- 2.1 kg). Baseline measurements were obtained from countermovement jumps, 15 s repeated jumps and 5 and 15 m sprints. A total of 36 min was analysed for each SSG (4v4 + GK: two sets of 3 * 6 min, and 8v8 + GK: 2 * 18 min). Heart rate, blood lactate, perceived exertion and movement pattern (GPS) were analysed. Distances covered by very-high-intensity activities and very-high-speed running were lower in 4v4 + GK than in 8v8 + GK (effect sizes (ES) = -0.69 +/- 0.67 and -1.04 +/- 0.67, respectively; very likely), while accelerations and decelerations were higher in 4v4 + GK than in 8v8 + GK (ES = 1.13-1.52; almost certainly). Blood lactate concentrations were higher (ES = 1.40 +/- 0.58; almost certainly) and players perceived themselves to be more tired (ES = 0.80-2.31; almost certainly) after 4v4 + GK than after 8v8 + GK. Sprint ability in 5 and 15 m tests decreased (ES = 0.87 +/- 0.58 and 0.89 +/- 0.58, respectively; almost certainly) only after 4v4 + GK. This SSG format appeared more demanding in relation to repetitions and fatigue development of muscle power based actions than 8v8 + GK. It may therefore be logical to use the former type of SSG to target development of power-related football actions. PMID- 27278257 TI - Fuse-binding protein 1 is a target of the EZH2 inhibitor GSK343, in osteosarcoma cells. AB - Osteosarcoma is the primary cancer of leaf tissue and is regarded as a differentiation disease caused by genetic and epigenetic changes which interrupt the osteoblast differentiation from mesenchymal stem cells. Because of its high malignancy degree and rapid development, the morbidity and mortality are high. The enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of polycomb repressive complex 2 (PRC2) and has been demonstrated to be involved in a variety of biological processes, such as cell proliferation and program cell death. EZH2 impairs gene expression by catalyzing the tri-methylation of histone H3 lysine 27 (H3K27me3) which controls gene transcription epigenetically. It is reported that EZH2 expression is higher in osteosarcoma than in osteoblastoma and the highest expression of EZH2 is found in osteosarcoma with metastasis. In the past few years, several potent inhibitors of EZH2 have been discovered, and GSK343 is one of them. In this study, we found that GSK343 inhibited osteosarcoma cell viability, restrained cell cycle transition and promoted programmed cell death. GSK343 not only inhibited the expression of EZH2 and its target, c-Myc and H3K27me3, but it also inhibited fuse binding protein 1 (FBP1) expression, another c-Myc regulator. Furthermore, we found that FBP1 physically interacts with EZH2. Based on these results, we believe that GSK343 is a potential molecule for osteosarcoma clinical treatment. Other than the inhibition on EZH2-c-Myc signal pathway, we postulate that the inhibition on FBP1-c-Myc signal pathway is another potential underlying mechanism with which GSK343 inhibits osteosarcoma cell viability. PMID- 27278258 TI - Plexciton Dirac points and topological modes. AB - Plexcitons are polaritonic modes that result from the strong coupling between excitons and plasmons. Here, we consider plexcitons emerging from the interaction of excitons in an organic molecular layer with surface plasmons in a metallic film. We predict the emergence of Dirac cones in the two-dimensional band structure of plexcitons due to the inherent alignment of the excitonic transitions in the organic layer. An external magnetic field opens a gap between the Dirac cones if the plexciton system is interfaced with a magneto-optical layer. The resulting energy gap becomes populated with topologically protected one-way modes, which travel at the interface of this plexcitonic system. Our theoretical proposal suggests that plexcitons are a convenient and simple platform for the exploration of exotic phases of matter and for the control of energy flow at the nanoscale. PMID- 27278259 TI - Chemoenzymatic synthesis and pH-responsive properties of amphoteric block polysaccharides. AB - Here, we investigated the chemoenzymatic synthesis of alpha(1->4)-linked amphoteric block polysaccharides. Amylouronic acid as an acidic block was first synthesized by 2,2,6,6-tetramethylpiperidine 1-oxyl-mediated oxidation of a water soluble amylose (chemical reaction). A short maltooligosaccharide chain, serving as an initiating site for the following enzymatic polymerization, was then introduced at the nonreducing end of the product by thermostable alpha-glucan phosphorylase-catalyzed enzymatic oligomerization of alpha-d-glucose 1-phosphate. Finally, thermostable alpha-glucan phosphorylase-catalyzed enzymatic polymerization of alpha-d-glucosamine 1-phosphate from the produced primer provided a basic block at the nonreducing end, leading to the desired amphoteric block polysaccharides. The structures of the products at each step were determined by (1)H NMR analysis. Furthermore, amphoteric products exhibited specific inherent isoelectric points (pIs). When the pH-responsive properties in aqueous solutions were evaluated using a divalent acid and base, similar hierarchical assembling/disassembling processes were observed by shifting the pH values from the pI to both the acidic and basic pH. PMID- 27278260 TI - Optimal Environmental Conditions and Anomalous Ecosystem Responses: Constraining Bottom-up Controls of Phytoplankton Biomass in the California Current System. AB - In Eastern Boundary Current systems, wind-driven upwelling drives nutrient-rich water to the ocean surface, making these regions among the most productive on Earth. Regulation of productivity by changing wind and/or nutrient conditions can dramatically impact ecosystem functioning, though the mechanisms are not well understood beyond broad-scale relationships. Here, we explore bottom-up controls during the California Current System (CCS) upwelling season by quantifying the dependence of phytoplankton biomass (as indicated by satellite chlorophyll estimates) on two key environmental parameters: subsurface nitrate concentration and surface wind stress. In general, moderate winds and high nitrate concentrations yield maximal biomass near shore, while offshore biomass is positively correlated with subsurface nitrate concentration. However, due to nonlinear interactions between the influences of wind and nitrate, bottom-up control of phytoplankton cannot be described by either one alone, nor by a combined metric such as nitrate flux. We quantify optimal environmental conditions for phytoplankton, defined as the wind/nitrate space that maximizes chlorophyll concentration, and present a framework for evaluating ecosystem change relative to environmental drivers. The utility of this framework is demonstrated by (i) elucidating anomalous CCS responses in 1998-1999, 2002, and 2005, and (ii) providing a basis for assessing potential biological impacts of projected climate change. PMID- 27278261 TI - Availability and Accessibility of Student-Specific Weight Loss Programs and Other Risk Prevention Health Services on College Campuses. AB - BACKGROUND: More than one third of college students who are overweight or obese are in need of weight loss programs tailored to college students. However, the availability and accessibility of these programs is unknown. OBJECTIVE: The aim of this study is to examine the availability and ease of access to weight loss programs for students at 10 universities with the largest undergraduate enrollment. METHODS: The 10 public universities with the largest student bodies with a mean (SD) undergraduate enrollment of 41,122 (7657) students were examined. The websites of the universities were assessed to determine the availability of weight loss programs. Services for high-risk health needs common to university campuses (ie, alcohol and other drugs, victim services, sexual health, and eating disorders) were searched. RESULTS: Of the universities searched, 3 (30%, 3/10) offered weight loss programming, however, none met the predetermined criteria. Comparatively, all schools (100%, 10/10) offered no-cost and continual enrollment programming for the other high-risk health needs. CONCLUSIONS: There are limited weight loss services available to undergraduate students compared with other university services. Collaboration between existing college health service providers is suggested for the delivery of appropriate programming for overweight and obese undergraduates wanting to lose weight. PMID- 27278262 TI - An Epicardial Mass of Unlikely Etiology. PMID- 27278263 TI - Sleep biosignature of Type 2 diabetes: a case-control study. AB - AIM: To determine whether or not the sleep disturbances associated with Type 2 diabetes affect the structure of sleep. METHODS: We designed a case-control study in 76 patients with Type 2 diabetes and 76 control subjects without Type 2 diabetes, matched by age, gender, BMI and waist and neck circumferences. A subgroup of 32 patients with Type 2 diabetes was also matched with 64 control subjects without Type 2 diabetes according to apnoea-hypopnoea index score. Examination included an overnight full polysomnography. RESULTS: No differences in the percentage of time spent in either rapid eye movement or non-rapid eye movement sleep were observed between groups; however, patients with Type 2 diabetes had more microarousal events during sleep than control subjects [41.4 (total range 4.0-104.4) vs 20.7 (total range 1.3-94.5) events/h; P < 0.001]. These differences were mainly observed during the non-rapid eye movement sleep [7.4 (total range 0-107.2) vs 0.2 (total range 0-65.2) events/h; P < 0.001]. In addition, sleep variables related to oxygen saturation measures, such as the percentage of time spent with oxygen saturation <=90%, were significantly greater during the rapid eye movement sleep in patients with Type 2 diabetes [20.3 (total range 0-99.2) vs. 10.5 (total range 0-94.0)%; P = 0.047]. This pattern was maintained in the subgroup of patients matched by apnoea-hypopnaea index. Finally, stepwise regression analyses showed that apnoea-hypopnoea index, the presence of Type 2 diabetes and fasting plasma glucose value were independently associated with the number of microarousals (R2 =0.667). CONCLUSIONS: Type 2 diabetes is associated with an altered sleep structure, with different effects according to rapid eye movement (increase in nocturnal hypoxia) or non-rapid eye movement (increase in sleep fragmentation) sleep. PMID- 27278265 TI - Complete exon 2 sequence of the HLA-DPA1*03:01 allele by sequence-based typing. AB - Completion of the first 20 nucleotides of exon 2 of DPA1*03:01 allele. PMID- 27278264 TI - Lung Transplant Center Volume Ameliorates Adverse Influence of Prolonged Ischemic Time on Mortality. AB - The influence of prolonged ischemic time on outcomes after lung transplant is controversial, but no research has investigated ischemic time in the context of center volume. We used data from the United Network for Organ Sharing to estimate the influence of ischemic time on patient survival conditional on center volume in the post-lung allocation score era (2005-2015). The analytic sample included 14 877 adult lung transplant recipients, of whom 12 447 were included in multivariable survival analysis. Patient survival was improved in high-volume centers compared with low-volume centers (log-rank test p = 0.001), although mean ischemic times were longer at high-volume centers (5.16 +/- 1.70 h vs. 4.83 +/- 1.63 h, p < 0.001). Multivariable Cox proportional hazards regression stratified by transplant center found an adverse influence of longer ischemic time at low volume centers but not at high-volume centers. At centers performing 50 transplants in the period 2005-2015, for example, 8 versus 6 h of ischemia were associated with an 18.9% (95% confidence interval 6.5-32.7%; p < 0.001) greater mortality hazard, whereas at centers performing 350 transplants in this period, no differences in survival by ischemic time were predicted. Despite longer mean ischemic time at high-volume transplant centers, these centers had favorable patient outcomes and no adverse survival implications of prolonged ischemia. PMID- 27278266 TI - Diagnostic reference levels for common paediatric fluoroscopic examinations performed at a dedicated paediatric Australian hospital. AB - INTRODUCTION: Diagnostic reference levels (DRL) of procedures involving ionising radiation are important tools for optimising radiation doses delivered to patients and to identify cases where the levels of dose are unusually high. This is particularly important for paediatric patients undergoing fluoroscopic examinations as these examinations can be associated with a high radiation dose. In this study, a large amount of paediatric fluoroscopic data has been analysed to: establish local DRL, identify the most significant factors determining radiation dose to patients, and modify fluoroscopic techniques to optimise the examination protocols. METHODS: Paediatric fluoroscopic studies performed at our institution from April 2010 to May 2015 have been retrospectively analysed to determine range, mean, 75th and 95th percentiles of Dose-Area Product (DAP) and fluoroscopic screening time for Micturating Cystourethrography (MCU), Airway, Airway and Swallow, Barium Swallow and Meal, Barium Follow Through and Barium Enema studies. RESULTS: Currently, no Australian paediatric fluoroscopic DRL data are available for comparison and thus our data can only be compared with international published data. No major changes to examination protocols or modification to fluoroscopic techniques were found necessary as our data compared well with the international published values. CONCLUSION: The dose delivered to patients depend on a number of factors particularly the experience of the operators. However, DRL are also important, as shown in this study, as they enable best practice by providing feedback to the operators on their performance and benchmarking the institution with other institutions. PMID- 27278267 TI - Prussian blue type nanoparticles for biomedical applications. AB - Prussian blue type nanoparticles are exciting nano-objects that combine the advantages of molecule-based materials and nanochemistry. Here we provide a short overview focalizing on the recent advances of these nano-objects designed for biomedical applications and give an outlook on the future research orientations in this domain. PMID- 27278268 TI - Kit receptor tyrosine kinase dysregulations in feline splenic mast cell tumours. AB - This study investigated Kit receptor dysregulations (cytoplasmic immunohistochemical expression and/or c-KIT mutations) in cats affected with splenic mast cell tumours. Twenty-two cats were included. Median survival time was 780 days (range: 1-1219). An exclusive splenic involvement was significantly (P = 0.042) associated with longer survival (807 versus 120 days). Eighteen tumours (85.7%) showed Kit cytoplasmic expression (Kit pattern 2, 3). Mutation analysis was successful in 20 cases. Fourteen missense mutations were detected in 13 out of 20 tumours (65%). Eleven (78.6%) were located in exon 8, and three (21.6%) in exon 9. No mutations were detected in exons 11 and 17. Seven mutations corresponded to the same internal tandem duplication in exon 8 (c.1245_1256dup). Although the association between Kit cytoplasmic expression and mutations was significant, immunohistochemistry cannot be considered a surrogate marker for mutation analysis. No correlation was observed between c-Kit mutations and tumour differentiation, mitotic activity or survival. PMID- 27278269 TI - Serum copeptin in children exposed to maltreatment. AB - AIM: Childhood maltreatment (CM) has been related to a persistent reprograming of stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activation; however, few studies have examined copeptin levels in children exposed to CM. The aim of this study was to compare serum copeptin levels in children reporting child abuse and/or neglect and children with no history of CM. METHODS: This study included 65 children with a positive history of moderate to severe CM, as reported by themselves and their parent(s) during a clinical interview, and 71 children with no history of CM as a comparison group. CM was considered moderate to severe based on the child-reported frequency of being exposed to events related to sexual abuse, physical abuse, emotional abuse, emotional neglect, and/or physical neglect. Child psychopathology symptoms were assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin concentration using enzyme-linked immunosorbent assay. RESULTS: Children exposed to CM exhibited higher levels of serum copeptin compared to children without CM when controlling for sex, age, and psychiatric morbidity. The CBCL total score, including internalizing and externalizing symptoms, was higher in children with CM. We found no correlation between copeptin and CBCL scores for internalizing symptoms and externalizing symptoms. CONCLUSION: CM is associated with copeptin serum levels independently of age, sex, and symptom severity. Copeptin is a promising new biomarker for children with a history of abuse and/or neglect. PMID- 27278270 TI - Echocardiographic outcomes of self-expandable CoreValve versus balloon-expandable Edwards SAPIEN XT valves: the comparison of two bioprosthesis implanted in a single centre. AB - Transcatheter aortic valve implantation (TAVI) with self-expandable Medtronic CoreValve (MCV; Medtronic, Minneapolis, MN) or balloon-expandable Edwards SAPIEN XT valve (ESV; Edwards Lifesciences, Irvine, CA) has been widely used for treatment of high-risk patients with severe aortic stenosis (AS). There is limited data comparing the long-term hemodynamic performance of these two valves. Therefore, this study aimed to compare the short and long-term hemodynamic performance of TAVI with either MCV or ESV. A total of 78 patients who underwent TAVI in our center between June 01, 2012 and January 01, 2014 were enrolled in this retrospective study. For each of the patients we recorded the preprocedural echocardiographic data as well as the post-TAVI echocardiographic outcomes at day one, 6 months and 1 year. The MCV group had lower transaortic gradients than the ESV group, with respect to both maximum (13.4 +/- 5.8 vs 18.7 +/- 8.1 mmHg, p = 0.001) and mean values (6.5 +/- 3.2 vs 9.4 +/- 4.3 mmHg, p < 0.001) at post-TAVI day one. These values continued to be significantly lower in the MCV group during post-TAVI 6 months (p < 0.001) and post-TAVI 1 year follow-up (p < 0.05). A paravalvular leak (PVL, grade >=2) was observed in 6.4 % of patients after TAVI; however, this value decreased over time, and there was no significant difference between the MVC and ESV groups (8.2 vs 3.4 %, p = 0.646). The MCV bioprosthesis was associated with lower transaortic gradients than those of the ESV throughout 1 year of follow-up. The incidence of PVL grade >=2 in MCV and ESV was comparable. PMID- 27278271 TI - Qualitative assessment of information and decision support needs for managing menopausal symptoms after breast cancer. AB - PURPOSE: For breast cancer (BrCa) survivors, premature menopause can result from conventional cancer treatment. Due to limited treatment options, survivors often turn to complementary therapies (CTs), but struggle to make informed decisions. In this study, we identified BrCa survivors' CT and general information and decision-making needs related to menopausal symptoms. METHODS: The needs assessment was informed by interpretive descriptive methodology. Focus groups with survivors (n = 22) and interviews with conventional (n = 12) and CT (n = 5) healthcare professionals (HCPs) were conducted at two Canadian urban cancer centers. Thematic, inductive analysis was conducted on the data. RESULTS: Menopausal symptoms have significant negative impact on BrCa survivors. Close to 70 % of the sample were currently using CTs, including mind-body therapies (45.5 %), natural health products (NHPs) and dietary therapies (31.8 %), and lifestyle interventions (36.4 %). However, BrCa survivors reported inadequate access to information on the safety and efficacy of CT options. Survivors also struggled in their efforts to discuss CT with HCPs, who had limited time and information to support women in their CT decisions. Concise and credible information about CTs was required by BrCa survivors to support them in making informed and safe decisions about using CTs for menopausal symptom management. CONCLUSIONS: High quality research is needed on the efficacy and safety of CTs in managing menopausal symptoms following BrCa treatment. Decision support strategies, such as patient decision aids (DAs), may help synthesize and translate evidence on CTs and promote shared decision-making between BrCa survivors and HCPs about the role of CTs in coping with menopause following cancer treatment. PMID- 27278272 TI - Relationship between severity and duration of chemotherapy-induced neutropenia and risk of infection among patients with nonmyeloid malignancies. AB - PURPOSE: Chemotherapy-induced neutropenia (CIN) may increase infection risk for cancer patients; however, there is limited understanding on the quantitative relationships between severity and duration of CIN and infection risk. METHODS: This study combined individual data from adult cancer patients receiving no granulocyte colony-stimulating factor during the first chemotherapy cycle in six trials. We used area over the curve (AOC) of absolute neutrophil count (ANC) time response curve (below different thresholds) to measure the combined effect of severity and duration of CIN. Time-dependent Cox proportional hazards models quantified the hazard of first infection associated with duration of grade 4 or grade 3/4 CIN and the hazard associated with AOC. RESULTS: We analyzed data from 271 patients who had small cell lung cancer, non-Hodgkin's lymphoma, head and neck cancer, or breast cancer; 63.8 % of the patients had advanced cancer, and 77.5 % received chemotherapy regimens with high risk of febrile neutropenia. In the first cycle, 18.8 % of the patients had infection-related hospitalizations. Each additional day patients had grade 3/4 or grade 4 CIN was associated with 28 % (95 % CI 7, 51 %) and 30 % (95 % CI 10, 54 %) increased risk of infection related hospitalization, respectively. Each unit increase in AOC (day * 10(9)/L ANC), with threshold of ANC < 0.5 * 10(9)/L, was associated with a significantly increased risk of infection-related hospitalization (hazard ratio 1.98; 95 % CI 1.35, 2.90). CONCLUSIONS: Infection risk increases dramatically with each additional day of grade 3 or 4 CIN. Interventions limiting CIN severity and duration are of critical importance to reduce infection risk in cancer patients receiving chemotherapy. PMID- 27278274 TI - Erratum to: Complex management of resistant oral herpes simplex virus infection following hematopoietic stem cell transplantation: potential role of topical cidofovir. PMID- 27278273 TI - Gaps exist between patients' experience and clinicians' awareness of symptoms after chemotherapy: CINV and accompanying symptoms. AB - INTRODUCTION: Correlating patients' chemotherapy-induced nausea and vomiting (CINV) experience with clinicians' understanding of the symptom severity and the patients' and clinicians' symptom management goals would aid in advancing symptom management. Identifying rankings of symptom severity after chemotherapy would help prioritizing symptom management. OBJECTIVE: The purpose of this study was to investigate and compare patients' CINV experience and clinicians' awareness of symptoms and symptom management goals. The study also aimed to identify and compare rankings of the severity of symptoms after chemotherapy by patients and clinicians. METHODS: A prospective observational study was conducted. Cancer patients starting the first adjuvant highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) (n = 313), and oncology clinicians at two university hospitals (n = 73) in Korea participated in the study. The Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) items and 20-symptom list were used to generate a symptom diary and survey questions. Descriptive statistics with a 95 % confidence interval and the Mann Whitney U test were used to analyze the data. RESULTS: In general, clinicians overestimated the patients' CINV experience. Patients' symptom experiences and clinicians' estimates only corresponded for delayed nausea after the second cycle MEC. For symptom management goals, patients aimed for absolute vomiting control and avoiding significant nausea. Patients' symptom management goals exceeded the clinicians' goals for CINV control except for the goal for delayed nausea control. Clinicians rated chemotherapy-induced nausea as the most problematic symptom followed by vomiting; however, fatigue and loss of appetite were the top rated symptoms by patients. CONCLUSIONS: Gaps exist between patients' symptom experience and clinicians' symptom awareness. Clinicians overestimated the patients' CINV experience and set less stringent symptom control goals. Enhancing clinicians' understanding of patients' symptom experience and retargeting the CINV management goals are the next steps for advancing symptom management. Symptoms other than CINV require more attention to set symptom management priorities reflecting patient experience and clinical significance. PMID- 27278275 TI - Cognitive Limitations at Work Among Employed Breast Cancer Survivors in China. AB - PURPOSE: This study aimed to determine whether levels of distress (anxiety and depression) and cognitive symptoms at work are related to work productivity and quality of life (QOL) in Chinese breast cancer survivors (BCS), compared to a group of Chinese women without cancer but with different musculoskeletal pain related to work. DESIGN: This study used a cross-sectional study design. METHODS: Working BCS were recruited in a tumor hospital's outpatient department, and women with no history of cancer (noncancer comparison [NCC] group) were recruited from a rehabilitation center. FINDINGS: A total of 412 participants were included. Multiple regression analyses indicated that higher anxiety was associated with work limitations (B = .005, p = .014) and QOL (B = 2.417, p = .004) in the BCS group only. Cognitive limitations at work were associated with work limitations (B = .002, p = .001) and QOL (B = 1.022, p = .003) in the BCS group only. Depressive symptoms (B = .028, p = .017) were significantly associated with work limitations in the NCC group. CONCLUSIONS: Breast cancer survivors reported higher levels of cognitive limitations at work and anxiety, lower levels of work productivity, and QOL. CLINICAL RELEVANCE: When remaining at work is a viable option for the cancer survivor with cognitive limitations at work, the rehabilitation nurse should consider approaches to best accommodate the specific cognitive limitations and work tasks, as well as help the patient manage associated anxiety when present. PMID- 27278278 TI - Proteomic analysis of mTOR inhibition-mediated phosphorylation changes in ribosomal proteins and eukaryotic translation initiation factors. PMID- 27278277 TI - Instrumental indices for upper limb function assessment in stroke patients: a validation study. AB - BACKGROUND: Robotic exoskeletons are increasingly being used in objective and quantitative assessment of upper limb (UL) movements. A set of instrumental indices computed during robot-assisted reaching tasks with the Armeo(r)Spring has been proven to assess UL functionality. The aim of this study was to test the construct validity of this indices-based UL assessment when used with patients who have had a stroke. METHODS: Forty-four 45- to 79-year-old stroke patients with a Wolf Motor Function Test ability score (WMFT-FAS) ranging from 10 to 75 and a Motricity Index (MI) ranging from 14 to 33 at shoulder and elbow were enrolled, thus covering a wide range of impairments. Residual UL function was assessed by both the WMFT-FAS and the WMFT-TIME, as well as by a set of 9 numerical indices assessing movement accuracy, velocity and smoothness computed from a 3D endpoint trajectory obtained during the "Vertical Capture" task of the Armeo(r)Spring device. To explore which variables better represented motor control deficits, the Mann-Whitney U Test was used to compare patients' indices to those obtained from 25 healthy individuals. To explore the inner relationships between indices and construct validity in assessing accuracy, velocity and smoothness, a factor analysis was carried out. To verify the indices concurrent validity, they were compared to both WMFT-FAS and WMFT-TIME by the Spearman's correlation coefficient. RESULTS: Seven indices of stroke subjects were significantly different from those of healthy controls, with effect sizes in the range 0.35-0.74. Factor analysis confirmed that specific subsets of indices belonged to the domains of accuracy, velocity and smoothness (discriminant validity). One accuracy index, both velocity indices and two smoothness indices were significantly correlated with WMFT-FAS and WMFT-TIME (|rho| = 0.31-0.50) (concurrent validity). One index for each of the assessed movement domains was proven to have construct validity (discriminant and concurrent) and was selected. Moreover, the indices were able to detect differences in accuracy, velocity and/or smoothness in patients with the same WMFT level. CONCLUSIONS: The proposed index-based UL assessment can be used to integrate and support clinical evaluation of UL function in stroke patients. PMID- 27278279 TI - A capital Scot: microscopes and museums in Robert E. Grant's zoology (1815-1840). AB - Early nineteenth-century zoology in Britain has been characterized as determined by the ideological concerns of its proponents. Taking the zoologist Robert E. Grant as an exemplary figure in this regard, this article offers a differently nuanced account of the conditions under which natural-philosophical knowledge concerning animal life was established in post-Napoleonic Britain. Whilst acknowledging the ideological import of concepts such as force and law, it points to an additional set of concerns amongst natural philosophers - that of appropriate tool use in investigation. Grant's studies in his native Edinburgh relied heavily on the use of microscopes. On his arrival in London, however, he entered a culture in which a different set of objects - museum specimens - held greater persuasive power. This article relates changes in Grant's ideas and practices to the uneven emphases on microscopic and museological evidence amongst European, Scottish and English natural philosophers at this time. In so doing, it identifies the reliance of London-based natural philosophers on museology as constituting a limiting effect on the kinds of claim that Grant sought to make regarding the nature of life. PMID- 27278280 TI - Fear of hypoglycemia, anxiety, and subjective well-being in parents of children and adolescents with type 1 diabetes. AB - This study explored the association between parental fear of hypoglycemia, anxiety, and subjective well-being in parents of children and adolescents with type 1 diabetes. A total of 120 mothers and 79 fathers participated. Mothers' and fathers' fear of hypoglycemia was significantly associated with anxiety and negative affect as well as with worse glycemic control in child. Paired-samples t test showed that mothers were more involved in diabetes management and reported more fear and anxiety compared to fathers, but they did not differ in worries about hypoglycemia. The findings suggest screening for fear of hypoglycemia and subjective well-being in all parents regardless of whether their child experienced severe hypoglycemia. PMID- 27278276 TI - The influence of a home-based exercise intervention on human health indices in individuals with chronic spinal cord injury (HOMEX-SCI): study protocol for a randomised controlled trial. AB - BACKGROUND: Spinal cord injury (SCI) creates a complex pathology that can lead to an increase in sedentary behaviours and deleterious changes in body composition. Consequently, individuals with SCI are at increased risk of developing cardiovascular disease and type-2 diabetes mellitus. While the role of physical activity on the reduction of chronic disease risk is well documented in non disabled individuals the evidence is less conclusive for persons with SCI. The aim of this methodological paper is to outline the design of a study that will assess the role of a home-based exercise intervention on biomarkers of metabolic and cardiovascular health in persons with SCI: the HOMEX-SCI study. METHODS/DESIGN: Eligible participants will be inactive (physical activity level <=1.60) individuals, with a chronic (more than 1 year) spinal cord lesion between the second thoracic and the fifth lumbar vertebrae, and aged between 18 and 65 years. Following baseline laboratory testing and lifestyle monitoring, participants will be randomly allocated to a control (CON) group or a 6-week home based exercise intervention (INT) group. The INT consists of 45 minutes of moderate-intensity (60-65 % peak oxygen uptake) arm-crank exercise four times per week. Participants assigned to the CON group will be asked to maintain their normal lifestyle. The main outcomes of this study (biomarkers of metabolic and cardiovascular health) are obtained from venous blood samples, collected in the fasted and postprandial state. Eight other measurement categories will be assessed: (1) body composition, (2) physical activity, (3) energy intake, (4) measures of health and wellbeing, (5) resting metabolic rate, heart rate and blood pressure, (6) aerobic capacity, (7) immune function, and (8) adipose tissue gene expression. DISCUSSION: This study will explore the feasibility of home based moderate-intensity exercise and ascertain its impact on metabolic and cardiovascular health in comparison to a lifestyle maintenance CON group. Findings from this study may help to inform new evidence-based physical activity guidelines and also help to elucidate the physiological mechanisms whereby exercise might exert beneficial effects in persons with chronic SCI. The results will also act as a scientific platform for further intervention studies in other diverse and at-risk populations. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN57096451 . Registered on 11 July 2014. PMID- 27278281 TI - Excellent response to deep brain stimulation in a young girl with GNAO1-related progressive choreoathetosis. PMID- 27278282 TI - Complete absence of the roof of the third ventricle in a case of hydrocephalus: an endoscopic view. PMID- 27278283 TI - Outcome of ventriculoperitoneal shunt and predictors of shunt revision in infants with posthemorrhagic hydrocephalus. AB - OBJECT: Ventriculoperitoneal (VP) shunts in infants with posthemorrhagic hydrocephalus (PHH) are prone to failures, with some patients at risk for multiple revisions. The objective of our study is to observe long-term outcomes and identify factors leading to proximal and distal multiple failures. METHODS: We performed a retrospective review of infants with PHH that required VP shunt placement between 1982 and 2014. These patients were monitored clinically and radiographically after VP shunt placement. RESULTS: A total of 502 surgical procedures (initial shunt insertion and revisions) were performed, with 380 shunt revisions in 102 (84 %) patients. Median shunt survival time was 54 months (0.03 220 months). Shunt survival was significantly affected by the following factors: intraventricular hemorrhage (IVH, grade II-III, 95 months vs. grade IV, 28 months, p = 0.022), birth weight (<1.5 kg, 59 months vs. >1.5 kg, 22 months, p = 0.005), gestational age (>27 weeks, 90 months vs. <27 weeks, 20 months, p < 0.0001), distal vs. proximal revision (133 months vs. 48 months, p = 0.013), obstruction (yes, 78 months vs. no, 28 months, p = 0.007), and infection (no, 75 months vs. yes, 39 months, p = 0.045). Regression analysis revealed that multiple gestation, head circumference (>27 cm), congenital anomalies, infection, and obstruction increased the proximal and distal shunt malfunction. CONCLUSION: Long term outcome of VP shunt placement in infants revealed a relatively high rate of complications requiring shunt revision as late as 30 years after initial placement. Infants with VP shunts should be monitored lifelong of these patients by neurosurgeons. PMID- 27278284 TI - Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA MB-231 human breast cancer cells. AB - The aim of the present study was to investigate the expression of matrix metalloproteinase (MMP)9 and MMP2, and their potential roles in bone metastasis nests using a well-standardized model of breast cancer bone metastasis in nude mice. BALB/c nu/nu mice (5-week-old; n=10) were subjected to intracardiac injection of MDA-MB-231 human breast cancer cells. After 4 weeks, the mice exhibiting radiolucent lesions in tibiae were sacrificed, and the tibiae were removed for histochemical analysis. The gene expression of MMP2 and MMP9 in the tumor cells, metaphysis and diaphysis of normal BALB/c nu/nu mice were determined using reverse transcription-polymerase chain reaction analysis. The metastatic tumor tissue occupied almost the entire bone marrow cavity. Numerous tartrate resistant acid phosphatase-positive osteoclasts were found in the metastasized lesions. The invaded tumor cells positive for mammaglobin 1 exhibited different proliferation activities and apoptosis between the metaphysis and diaphysis. Proliferating cell nuclear antigen was expressed at high levels in the metaphyseal area, whereas TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were more evident in the diaphysis area. Of note, MMP9 was expressed predominantly in the proliferating cell nuclear antigen-positive area, whereas the expression of MMP2 was observed predominantly in the diaphysis, which had more TUNEL-positive cells. Taken together, the results suggested that MMP9 and MMP2 may have their own importance in extracellular matrix degradation and trabecular bone damage in different zones of bone metastasis, including the metaphysis and diaphysis. PMID- 27278286 TI - Remote Control Effect of Li(+), Na(+), K(+) Ions on the Super Energy Transfer Process in ZnMoO4:Eu(3+), Bi(3+) Phosphors. AB - Luminescent properties are affected by lattice environment of luminescence centers. The lattice environment of emission centers can be effectively changed due to the diversity of lattice environment in multiple site structure. But how precisely control the doped ions enter into different sites is still very difficult. Here we proposed an example to demonstrate how to control the doped ions into the target site for the first time. Alkali metal ions doped ZnMoO4:Bi(3+), Eu(3+) phosphors were prepared by the conventional high temperature solid state reaction method. The influence of alkali metal ions as charge compensators and remote control devices were respectively observed. Li(+) and K(+) ions occupy the Zn(2) sites, which impede Eu and Bi enter the adjacent Zn(2) sites. However, Na(+) ions lie in Zn(1) sites, which greatly promoted the Bi and Eu into the adjacent Zn(2) sites. The Bi(3+) and Eu(3+) ions which lie in the immediate vicinity Zn(2) sites set off intense exchange interaction due to their short relative distance. This mechanism provides a mode how to use remote control device to enhance the energy transfer efficiency which expected to be used to design efficient luminescent materials. PMID- 27278285 TI - Meta-analysis of the influence of TM6SF2 E167K variant on Plasma Concentration of Aminotransferases across different Populations and Diverse Liver Phenotypes. AB - A nonsynonymous E167K (rs58542926 C/T) variant in TM6SF2 gene was recently associated with nonalcoholic fatty liver disease (NAFLD). We explored the association between E167K and plasma concentrations of alanine (ALT) and aspartate (AST) aminotransferases through a meta-analysis. We also estimated the strength of the effect across diverse liver phenotypes, including NAFLD and chronic viral hepatitis; fourteen studies were included. We found that ALT (p = 3.2 * 10(-6), n = 94,414) and AST (p = 0007, n = 93,809) levels were significantly associated with rs58542926 in NAFLD. By contrast, rs58542926 was not associated with either ALT (p = 0.24, n = 4187) or AST (p = 0.17, n = 2678) levels in four studies on chronic hepatitis. In conclusion, the results of the pooled estimates in patients with NAFLD showed that carriers of the T allele (EK + KK), when compared with homozygous subjects for the C allele (EE genotype) have increased levels of aminotransferases; however, this increase represents -2.5 (9.8%) and 1.2 (5%) IU/L of ALT and AST respectively, which is fairly small compared with the large effect of PNPLA3- rs738409-G allele that is associated with a -28% increase in serum ALT. PMID- 27278288 TI - Editorial: The moral significance of antimicrobial resistance and the rise of 'apocalyptic superbugs'. PMID- 27278287 TI - Histone deacetyltransferase inhibitors Trichostatin A and Mocetinostat differentially regulate MMP9, IL-18 and RECK expression, and attenuate Angiotensin II-induced cardiac fibroblast migration and proliferation. AB - Histone acetylation/deacetylation plays a key role in the epigenetic regulation of multiple pro-fibrotic genes. Here we investigated the effects of histone deacetyltransferase (HDAC) inhibition on angiotensin (Ang)-II-induced pro fibrotic changes in adult mouse cardiac fibroblasts (CF). CF express class I HDACs 1 and 2, and Ang-II induces their activation. Notably, silencing HDAC1 or HDAC2 attenuated Ang-II induced CF proliferation and migration. Under basal conditions, HDAC1 dimerizes with HDAC2 in CF and Ang-II reversed this interaction. Treatment with Trichostatin A (TSA), a broad-spectrum HDAC inhibitor, restored their physical association, and attenuated Ang-II-induced MMP9 expression, IL-18 induction, and extracellular matrix (collagen I, collagen III and fibronectin) production. Further, TSA inhibited Ang-II-induced MMP9 and Il18 transcription by blocking NF-kappaB and AP-1 binding to their respective promoter regions. By inhibiting Sp1 binding to RECK promoter, TSA reversed Ang-II induced RECK suppression, collagen and fibronectin expression, and CF migration and proliferation. The class I-specific HDAC inhibitor Mocetinostat (MGCD) recapitulated TSA effects on Ang-II-treated CF. Together, these results demonstrate that targeting HDACs attenuates the pro-inflammatory and pro-fibrotic effects of Ang-II on CF. PMID- 27278289 TI - Correction: The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase. PMID- 27278290 TI - Debut of new contrast agent. PMID- 27278291 TI - Evaluation of malignancy of hepatocellular carcinoma using the ultrasonic B-mode method: clinical significance of extracapsular invasion of hepatocellular carcinoma using ultrasonography. AB - PURPOSE: To determine the influence of capsule formation or presence of capsular invasion on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The patient group consisted of 70 patients with 74 HCC lesions who had been examined by US and undergone surgical tumor resection at our institution. For these patients, we conducted the following comparative studies: (a) comparison between halo findings on US and microscopic capsular results; (b) comparison between halo findings on US and tumor diameter, tumor histological differentiation, and serum value of each tumor marker; and (c) comparison between halo findings on US and tumor recurrence. RESULTS: (a) The corresponding value between sonographic halo and histological capsule was 90.1%, and that between presence of extracapsular invasion on US and that seen by histology was 88.0%. (b) There was no relation between US images and histological differentiation of tumors. (c) Presence of extracapsular invasion on US was a predisposing factor for the development of tumor recurrence. CONCLUSION: (1) Globally speaking, sonographic halo corresponded to the histological tumor capsule. (2) In patients with extracapsular invasion, tumor recurrence after treatment increased. Thus, a better understanding of sonographic halo findings helps determine diagnostic and therapeutic strategies in HCC patients. PMID- 27278292 TI - Preperitoneal fat thickness by ultrasonography and obesity-related disorders. AB - PURPOSE: To determine optimal cutoff values for preperitoneal fat thickness measured by ultrasonography as indicators for obesity-related disorders. METHODS: We studied 276 men aged 60 +/- 13 years and 307 women aged 64 +/- 11 years. Participants were consecutively enrolled from inpatients aged <=75 years. Demographic data were collected and maximal preperitoneal fat thickness (PFTmax) and carotid intima-media thickness were evaluated on B-mode ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal cutoff values for PFTmax. RESULTS: Multiple regression analysis using one or more obesity-related disorders as an objective variable showed that the tertile on the basis of PFTmax was a significant independent contributing factor in both men and women. Receiver operating characteristic curve analysis identified the cutoff points of 6.1 mm for PFTmax in men (sensitivity, 66.7%; specificity, 62.5%) and 8.7 mm for PFTmax in women (sensitivity, 56.6%; specificity, 63.6%) as discriminator values corresponding to the presence of one or more obesity-related disorders. Using the new criteria to diagnose visceral obesity, we found that adjusted carotid intima-media thickness was significantly higher in men and women with visceral obesity and two or more obesity-related disorders than in those without them. CONCLUSIONS: These findings suggested that PFTmax measured on ultrasonography was useful in screening for indicators of cardiovascular risk factors. PMID- 27278293 TI - Clinical efficacy of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC). AB - PURPOSE: To evaluate the role of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC). METHODS: CEUS and angiography were performed in ten cases of ruptured HCC. We evaluated whether this technique allowed us to determine the bleeding point by observing an extravasation of contrast media into the ascites. RESULTS: In four of the ten cases, CEUS demonstrated an extravasation of Levovist into ascites. Angiography showed an extravasation of contrast medium in three of these four cases. In three of the remaining six cases, in which CEUS did not show the presence of contrast medium in ascites, angiography demonstrated an extravasation. In eight cases, it yielded cessation of bleeding. In two cases, embolization was not successful. The bleeding point was not determined by CEUS or angiography in one case. CONCLUSION: CEUS allows us to differentiate active bleeding (presence of contrast medium in the ascites) from nonactive bleeding. PMID- 27278295 TI - Rupture of liver metastasis: report of a case with an emphasis on contrast enhanced US. AB - We present a case of liver metastasis from an uterine leiomyosarcoma in which contrast-enhanced ultrasonography (CEUS) helped determine the bleeding point and prevented a delay in devising diagnostic and therapeutic strategies. CEUS allowed us to differentiate active from nonactive bleeding on the basis of presence or absence of contrast extravasation in the ascites. CEUS is the first examination performed when liver tumor rupture is suspected. Reference to the preangiographic CEUS results is expected to provide a road map for angiography. PMID- 27278294 TI - Malignant triton tumor in a patient with neurofibromatosis type 1. AB - We report a case of neurofibromatosis type 1 (NF1) complicated by a malignant triton tumor (MTT), with an emphasis on B-mode sonographic (US) and contrast enhanced US (CEUS) findings. To the best of our knowledge, this is the first report describing CEUS findings of MTT. The mass was poorly demarcated and composed of an internal echogenic area and an outer hypoechoic zone. CEUS findings showed the outer zone to be strongly enhanced, and the internal area was very poor in blood flow because of necrotic tissues. PMID- 27278297 TI - Examination guide for ultrasonic image presentation and measurement of the ophthalmic region. PMID- 27278296 TI - SMA invasion without SMV invasion in a pancreatic uncinate carcinoma. PMID- 27278299 TI - Modified Pulsatilla decoction attenuates oxazolone-induced colitis in mice through suppression of inflammation and epithelial barrier disruption. AB - Inflammatory bowel diseases (IBDs) are chronic inflammatory gastrointestinal disorders caused by a dysregulated mucosal immune response and epithelial barrier disruption. Conventional treatment of IBD is currently limited to overcoming patient symptoms and is often associated with severe adverse effects from the drugs used. Modified Pulsatilla decoction has been used previously to treat ulcerative colitis (UC) in clinical practice in China, however, the underlying mechanism in the treatment of UC remains to be elucidated. In the present study, the efficiency and mechanisms of modified Pulsatilla decoction in the treatment of oxazolone-induced colitis were investigated. Assessment of clinical colitis and histological examination found that the administration of modified Pulsatilla decoction attenuated the severity of oxazolone-induced colitis in mice. Measurement of cytokine concentration, western blotting and reverse transcription quantitative polymerase chain reaction demonstrated modified Pulsatilla decoction treatment significantly reduced the secretion of pro-inflammatory cytokines and restored alterations in tight junction proteins in the colon tissues. In addition, modified Pulsatilla decoction suppressed the activation of the nuclear factor-kappaB signaling pathway. Thus, the findings of the present study demonstrated that modified Pulsatilla decoction offers an effective therapeutic approach for the treatment of IBD and revealed the underlying mechanisms of action offered by modified Pulsatilla decoction. PMID- 27278300 TI - Impact of macronutrient composition and palatability in wet diets on food selection in cats. AB - Cats are obligate carnivores adapted to high-protein diets, but are commonly fed diets rich in carbohydrate. The aim of this study was to examine the food intake choices of cats when diets with different protein and carbohydrate contents were offered. Thirty-nine cats participated in voluntary dietary intake studies. Four foods were formulated to provide between 24% and 53% of metabolizable energy as protein, between 43% and 11% as carbohydrate and holding dietary fat constant with a contribution of approximately 36%. Foods were offered either singly to evaluate voluntary food intake or in pairs to compare food intake between pairs of diets. Cats regulated their macronutrient intake to attain an overall diet composition that provided 53% of metabolizable energy as protein, 11% as carbohydrate and 36% as fat. The protein contribution corresponded to approximately 6 g of protein/kg body weight/day. High-protein/low-carbohydrate diets were always eaten preferentially over low-protein/high-carbohydrate foods. When low-protein/high-carbohydrate diets were offered, cats limited their food intake to limit daily carbohydrate intake to less than 3 g of carbohydrate/kg body weight. This carbohydrate ceiling may limit protein and even energy intake when only low-protein/high-carbohydrate diets were offered. The inclusion of palatability enhancer in the diets increased food intake but did not change protein or carbohydrate intake patterns, indicating that macronutrient intake can be regulated regardless of the use of palatability enhancers in cats. We conclude that cats can discriminate between diets based on macronutrient composition and regulate their intake to maintain maximal protein intake but limit carbohydrate intake. PMID- 27278302 TI - The arts and science of ultrasound. PMID- 27278301 TI - Strong modulation of plasmons in Graphene with the use of an Inverted pyramid array diffraction grating. AB - An optical device configuration allowing efficient electrical tuning of surface plasmon wavelength and absorption in a suspended/conformal graphene film is reported. An underlying 2-dimensional array of inverted rectangular pyramids greatly enhances optical coupling to the graphene film. In contrast to devices utilising 1D grating or Kretchman prism coupling configurations, both s and p polarization can excite plasmons due to symmetry of the grating structure. Additionally, the excited high frequency plasmon mode has a wavelength independent of incident photon angle allowing multidirectional coupling. By combining analytical methods with Rigorous Coupled-Wave Analysis, absorption of plasmons is mapped over near infrared spectral range as a function of chemical potential. Strong control over both plasmon wavelength and strength is provided by an ionic gel gate configuration. 0.04eV change in chemical potential increases plasmon energy by 0.05 eV shifting plasmon wavelength towards the visible, and providing enhancement in plasmon absorption. Most importantly, plasmon excitation can be dynamically switched off by lowering the chemical potential and moving from the intra-band to the inter-band transition region. Ability to electrically tune plasmon properties can be utilized in applications such as on-chip light modulation, photonic logic gates, optical interconnect and sensing applications. PMID- 27278298 TI - Environmentally induced epigenetic toxicity: potential public health concerns. AB - Throughout our lives, epigenetic processes shape our development and enable us to adapt to a constantly changing environment. Identifying and understanding environmentally induced epigenetic change(s) that may lead to adverse outcomes is vital for protecting public health. This review, therefore, examines the present understanding of epigenetic mechanisms involved in the mammalian life cycle, evaluates the current evidence for environmentally induced epigenetic toxicity in human cohorts and rodent models and highlights the research considerations and implications of this emerging knowledge for public health and regulatory toxicology. Many hundreds of studies have investigated such toxicity, yet relatively few have demonstrated a mechanistic association among specific environmental exposures, epigenetic changes and adverse health outcomes in human epidemiological cohorts and/or rodent models. While this small body of evidence is largely composed of exploratory in vivo high-dose range studies, it does set a precedent for the existence of environmentally induced epigenetic toxicity. Consequently, there is worldwide recognition of this phenomenon, and discussion on how to both guide further scientific research towards a greater mechanistic understanding of environmentally induced epigenetic toxicity in humans, and translate relevant research outcomes into appropriate regulatory policies for effective public health protection. PMID- 27278303 TI - Errors in measuring blood flow velocity behind hepatic mass lesions using color doppler sonography. AB - The authors designed microcomputer simulation models to investigate the combined effect of a distorted grayscale ultrasound image and an inaccurately measured Doppler angle on the accuracy of measurement of blood-flow velocity in vessels located behind mass lesions in the liver. Error decreased when flow was measured at the midpoint of the posttumoral segment of the vessel and increased with distance between the mass and the vessel, with inclination of the vessel, and with decrease in the diameter of the mass. Error was least with the sector probe, intermediate with the convex probe, and greatest with the linear probe. These findings suggest that the error can be minimized when measuring blood flow velocity in a vessel located behind a mass, if the Doppler images are acquired using a sector probe from the midpoint of the posttumoral segment of the vessel. PMID- 27278304 TI - Detection of tumor vascularity in hepatocellular carcinoma with contrast-enhanced Dynamic Flow imaging: Comparison with contrast-enhanced power Doppler imaging. AB - OBJECTIVE: To compare the effectiveness of contrast-enhanced Dynamic Flow imaging and contrast-enhanced power Doppler imaging using Levovist((r)) as a microbubble contrast agent in evaluating intratumoral vascularity in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-nine patients with 54 hepatocellular carcinoma nodules (before treatment, 31; after treatment, 23) were studied with both Dynamic Flow and power Doppler imaging with intravenous injection of Levovist((r)). Tumor vascularity was categorized as 0, no blood flow signals within the tumor; 1, dotlike blood flow signals within the tumor; 2, moderate blood flow signals within the tumor; and 3, abundant blood flow signals within the tumor. Detectability of intratumoral vascularity of hepatocellular carcinoma in three groups based on tumor depth, blooming and noise artifacts on contrast enhanced Dynamic Flow and contrast-enhanced power Doppler imaging were also compared with results obtained using dynamic CT as a the gold standard. The effectiveness of contrast-enhanced Dynamic Flow and contrast-enhanced power Doppler imaging in assessing therapeutic effect were compared at the same time. RESULTS: The ability of contrast-enhanced Dynamic Flow Doppler imaging to detect tumor vascularity in the superficial and intermediate hepatocellular carcinoma groups was close to that of contrast-enhanced power Doppler imaging (p>0.05). However, contrast-enhanced Dynamic Flow imaging demonstrated tumor parenchymal stain in 28 hepatocellular carcinoma nodules (61%), which was not detected by contrast-enhanced power Doppler imaging. Further, significantly fewer artifacts appeared in contrast-enhanced Dynamic Flow imaging than in contrast-enhanced power Doppler imaging (p<0.001). In assessing therapeutic response, the sensitivity of contrast-enhanced Dynamic Flow imaging was similar to that of dynamic CT. In deep areas, however, those more than 6 cm below the surface of the body, contrast-enhanced Dynamic Flow imaging was less sensitivity than contrast enhanced power Doppler imaging (p=0.005). CONCLUSION: Contrast-enhanced Dynamic Flow imaging provides an effective approach to assessing intratumoral vascularity and therapeutic response in HCC lesions situated less than 6 cm from the surface of the body. It is superior to contrast-enhanced power Doppler imaging in its ability to detect tumor parenchymal stain and production of fewer artifacts. PMID- 27278305 TI - The usefulness of mesenterium thickness as an index of visceral fat accumulation. AB - Visceral fat syndrome, which includes visceral fat accumulation, glucose intolerance, hyperlipidemia, and hypertension, refers to a highly atherogenic state with a cluster of risk factors secondary to visceral fat accumulation. Although X-ray computed tomography (CT) is used commonly in diagnosis of visceral fat accumulation, it is expensive and exposes the patient to radiation. Some indices obtained using ultrasonography, which is fast and easy to use, have been reported. The ratio of the maximum thickness of preperitoneal fat (P) to the minimum thickness of subcutaneous fat (S), the abdominal wall fat index (P/S), is widely used in ultrasonographic diagnosis, however, this ratio tends to vary largely according to examiners. To establish a more reliable ultrasonographic index of visceral fat accumulation, we measured the thickness of the mesenterium, and tried to examine the relation between its thickness and maximum thickness of preperitoneal fat, minimum thickness of subcutaneous fat, and abdominal wall fat index, as well as body mass index, systolic and diastolic blood pressure, and levels of serum triglyceride, high-density lipoprotein cholesterol, total cholesterol, and blood sugar. The subjects were 131 individuals, 98 males and 33 females, averaging 47.0+/-7.9 years, with a mean body mass index of 24.1+/-2.6. The mesenterium was measured with a 3.5 or 3.75 MHz convex probe by longitudinal scanning on the left side of the umbilicus of the patient in the supine position. The thickness of the mesenterium correlated positively with maximum thickness of the preperitoneal fat, abdominal wall fat index, body mass index, and levels of serum triglyceride, total cholesterol, and blood sugar, and negatively with levels of high-density lipoprotein cholesterol. When the subjects were divided into a high-M group and a normal-M group, body mass index, triglyceride level, and blood sugar levels in the high-M group were significantly higher and level of high-density lipoprotein cholesterol was significantly lower than in the normal-M group. These results suggest that the thickness of mesenteium measured by ultrasonography may be useful in the diagnosis of accumulation of visceral fat. PMID- 27278306 TI - Ultrasonographic diagnosis of advanced colorectal cancer. AB - We investigated the efficacy of transabdominal ultrasonography for the diagnosis of advanced colorectal cancer. Colonic examination by colonoscopy, barium study, or surgery was carried out in our institution on 1579 patients during the past 5 years. This study focused on 1564 of these patients, 15 who has been diagnosed with colorectal cancer before ultrasound examination having been excluded. The results included 51 ultrasound-positive cases, 9 ultrasound-false-positive cases, 1476 ultrasound-negative cases, and 28 ultrasound-false-negative cases. Sensitivity was 64.6 percent and specificity was 99.6 percent. Of the 28 ultrasound-false-negative cases, the lesion was detected in the ascending colon in 2, in the transverse colon in 6, in the descending colon in 1, in the sigmoid colon in 3, and in the rectum in 16. Obstruction and dilatation suggested colorectal cancer in 3 cases, which were thus classified as ultrasound-negative when no tumors were detected. Sensitivity was investigated by site. Sensitivity was lowest at 30.4 percent in rectal cancer, but was 78.6 percent in colon cancer, exclusive of rectal cancer. Laboratory findings and clinical symptoms which were suggestive of colorectal cancer were used as information before ultrasound examination was performed. Sensitivity of examinations carried out on examinees on whom prior information was available and on those on whom there was no information did not differ significantly. Furthermore, ultrasound was thought to detect approximately 65 percent of advanced colorectal cancers when it was used aggressively to investigate the large intestine. Ultrasound was thus considered effective for detecting advanced colorectal cancer. PMID- 27278307 TI - Comparison of sonographic triplet fetal growth measurements between Japanese and American populations. AB - OBJECTIVE: To evaluate changes in several triplet fetal growth parameters associated with gestational age by means of a longitudinal study designed to compare ethnic differences in fetal growth in Japanese and American populations. SUBJECTS: Twenty-one Japanese triplet fetuses (7 triplet pregnancies) and 21 American triplet fetuses (7 triplet pregnancies). The Japanese pregnancies were in middle-class Japanese women living in the Kagawa area; the American pregnancies, in middle-class white women living in the Houston area. METHODS: Head circumference, abdominal circumference, femur length, and estimated weight were measured every 2 to 3 weeks from 15 weeks of gestational age until delivery. Values for each parameter at each gestational age were measured in each fetal group, and the data of the groups were compared. RESULTS: Head circumference, abdominal circumference, femur length, and estimated weight were significantly lower in the Japanese than in the American triplet fetuses after 20 weeks of gestation (p<0.01). CONCLUSION: These results suggest that triplet fetal growth in Japanese populations and American populations differs significantly in the second half of pregnancy. PMID- 27278308 TI - Measuring medium-sized muscular arteries using a novel broadband 15-MHz linear array probe. AB - We recently developed a wideband 15-MHz linear array probe (15 M) with a band width of 8 MHz (9-17 MHz). Both axial and lateral resolution of 15 M, evaluated using a phantom model, were better than those of the current 10-MHz linear probe. To compare interobserver variability in measurement of medium-sized muscular arteries acquired using a 7.5-MHz linear probe (7.5 M), a 10-MHz linear probe (10M) and 15 M, two observers independently acquired images of the brachial and radial arteries, and measured the diameter and intima-media thickness (IMT) of those arteries in 17 male volunteers. Intraobserver variability in determining percent flowmediated dilatation (%FMD) was assessed in the same subjects using 15 M. Coefficients of variation (CV) in arteries measured using 7.5 M, 10 M, and 15 M were 7.0%, 2.5%, and 1.5%, respectively, for the diameter of the brachial artery; 10.3%, 5.8%, and 3.2%, respectively, for the diameter of the radial artery; and 17.0%, 13.8%, and 8.5%, respectively, for IMT of the far wall of the brachial artery. The CV of measurement of %FMD was 4.6%. The new 15-MHz probe thus warrants use in evaluating morphology and function of muscular arteries of medium size. PMID- 27278309 TI - Sonographic measurement of renal length in children: Variation associated with body position. AB - We ultrasonographically measured renal length in the major axis in children. Here we discuss the differences in measured lengths in the supine and prone positions. In study 1, which included 214 children, more than 60 percent of the kidneys measured longer in the supine than in the prone position. The difference (S-P: length in the supine position minus length in the prone position) was substantially greater in the left kidney. In study 2, we observed the relation between the kidney and the liver or spleen in 60 children prospectively to determine if artifacts had contributed to the observed differences. When the location of the liver or spleen was above the ki dney, which may induce velocity displacement and renal duplication artifacts, the kidney tended to measure longer. We conclude that kidneys tend to measure longer in the supine than in the prone position. Difference in renal length in different positions was greater in the left kidney than in the right kidney. Sonographic artifacts are presumed to contribute to differences in measured length. PMID- 27278310 TI - A case of solitary necrotic nodule of the liver with acute liver dysfunction: The imaging appearance correlated with pathological findings. AB - A 22-year-old woman was admitted to this institution because of severe liver dysfunction that looked like acute hepatitis. Abdominal ultrasonography revealed a liver mass 20 mm in diameter that resembled the bull's-eye sign. Enhanced CT revealed a low-density mass. The mass was hypointense in T1-weighted MRI images and slightly hyperintense in T2-weighted MRI images. Needle biopsy of the liver under ultrasound guidance led to a diagnosis of solitary necrotic nodule of the liver. The tumor consisted of coagulation necrosis surrounded by fibrotic tissue. These pathologic features were consistent with the Imaging findings. PMID- 27278311 TI - Pulsed Doppler echocardiographic detection of the origin of musical murmurs in a case of pacemaker implantation. AB - We report a case of systolic and diastolic musical murmurs that developed 4 years after DDD pacemaker implantation. Echocardiographic examination disclosed no evidence of serious pacemaker-related complications. Pulsed Doppler examination with a sample volume at the right ventricular portion of a pacemaker lead showed prominent harmonic signals. The timing of the signals was consistent with that of musical murmurs. We considered vibration of the pacemaker lead as a possible origin of the musical murmurs. Systolic and diastolic musical murmurs can develop without serious cause in a patient with a transvenous pacemaker. Pulsed Doppler examination was useful in detecting the origin of musical murmurs. PMID- 27278313 TI - Executive Functions in Older Adults With Autism Spectrum Disorder: Objective Performance and Subjective Complaints. AB - Although deficits in Executive Functioning (EF) are reported frequently in young individuals with Autism Spectrum Disorders (ASD), they remain relatively unexplored later in life (>50 years). We studied objective performance on EF measures (Tower of London, Zoo map, phonetic/semantic fluency) as well as subjective complaints (self- and proxy reported BRIEF) in 36 ASD and 36 typically developed individuals (n = 72). High functioning older adults with ASD reported EF-impairments in metacognition, but did not deviate in EF task performance, except for a longer execution time of the Tower of London. The need for additional time to complete daily tasks may contribute to impairments in daily life and may be correlated to a higher level of experienced EF-difficulties in ASD. PMID- 27278328 TI - 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside suppresses human colorectal cancer cell metastasis through inhibiting NF-kappaB activation. AB - 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), a major component of Polygonum multiflorum Thunb (He-Shou-Wu), has been reported to exhibit antioxidant and anti-inflammatory effects. However, its anti-metastatic effect against colorectal cancer is still unclear. In this study, cell migration, invasion and adhesion abilities as well as metastasis-associated protein and NF kappaB pathway signaling factor expression were analyzed after treating HT-29 cells with THSG. According to the results, the migration and invasiveness of HT 29 cells were reduced after treatment with 5 or 10 mM THSG (p<0.05). Additionally, the levels of matrix metalloproteinase-2 (MMP-2) and phosphorylated VE-cadherin in HT-29 cells were reduced and the transepithelial electrical resistance (TEER) of EA.hy926 endothelial cell monolayers was increased after incubation in THSG for 24 h (p<0.05). Cell adhesion ability and the E-selectin and intercellular adhesion molecule-1 (ICAM-1) protein levels were reduced when EA.hy926 endothelial cells were treated with THSG (p<0.05). In addition, the cytoplasmic phosphorylation of IkappaB, the nuclear p65 level and the DNA-binding activity of NF-kappaB were reduced after treating HT-29 or EA.hy926 cells with 5 or 10 mM THSG (p<0.05). These results suggest that THSG inhibits HT-29 cell metastasis by suppressing cell migration, invasion and adhesion. Furthermore, THSG inhibits metastasis-associated protein expression by suppressing NF-kappaB pathway activation. PMID- 27278330 TI - Brain-derived neurotrophic factor delivered to the brain using poly (lactide-co glycolide) nanoparticles improves neurological and cognitive outcome in mice with traumatic brain injury. AB - Currently, traumatic brain injury (TBI) is the leading cause of death or disabilities in young individuals worldwide. The multi-complexity of its pathogenesis as well as impermeability of the blood-brain barrier (BBB) makes the drug choice and delivery very challenging. The brain-derived neurotrophic factor (BDNF) regulates neuronal plasticity, neuronal cell growth, proliferation, cell survival and long-term memory. However, its short half-life and low BBB permeability are the main hurdles to be an effective therapeutic for TBI. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles coated by surfactant can enable the delivery of a variety of molecules across the BBB by receptor-mediated transcytosis. This study examines the ability of PLGA nanoparticles coated with poloxamer 188 (PX) to deliver BDNF into the brain and neuroprotective effects of BNDF in mice with TBI. C57bl/6 mice were subjected to weight-drop closed head injuries under anesthesia. Using enzyme-linked immunosorbent assay, we demonstrated that the intravenous (IV) injection of nanoparticle-bound BDNF coated by PX (NP-BDNF-PX) significantly increased BDNF levels in the brain of sham-operated mice (p < 0.001) and in both ipsi- (p < 0.001) and contralateral (p < 0.001) parts of brain in TBI mice compared to controls. This study also showed using the passive avoidance (PA) test, that IV injection of NP-BDNF-PX 3 h post injury prolonged the latent time in mice with TBI thereby reversing cognitive deficits caused by brain trauma. Finally, neurological severity score test demonstrated that our compound efficiently reduced the scores at day 7 after the injury indicating the improvement of neurological deficit in animals with TBI. This study shows that PLGA nanoparticles coated with PX effectively delivered BDNF into the brain, and improved neurological and cognitive deficits in TBI mice, thereby providing a neuroprotective effect. PMID- 27278331 TI - Understanding biological systems using ultrasound: complex dynamical systems view. PMID- 27278332 TI - Contrast-enhanced 3D ultrasonography in minute hepatocellular carcinoma. AB - PURPOSE: The study aimed to clarify whether contrast-enhanced (CE) three dimensional (3D) ultrasonography (US) can depict characteristic hyperstain and washout patterns in minute nodules <=10 mm of hepatocellular carcinoma (minute HCC), and whether it serves as a potent diagnostic modality. METHODS: CE 3D US was carried out to depict hyperstain and washout of a solitary nodule <=10 mm in patients with liver cirrhosis. When both patterns were depicted with success, CE computed tomography (CT) and CE magnetic resonance imaging (MRI) were also carried out as part of a comparative study, and then a histological specimen was obtained by needle biopsy. The final diagnosis was based on the histopathological findings and a follow-up on the growth of nodules. RESULTS: All 12 minute nodules exhibiting hyperstain and washout showed evidence of HCC when examined by CE 3D US. The CE CT and CE MRI examinations could depict both of these patterns, characteristic of HCC, in most of the nodules but rather less successfully than CE 3D US. CONCLUSION: CE 3D US can depict hyperstain and washout patterns in minute HCC and serves as a potent modality for diagnosis. PMID- 27278333 TI - Integrated fibrosis scoring by ultrasonography predicts the occurrence of hepatocellular carcinoma in patients with chronic hepatitis C virus infection. AB - PURPOSE: This study was performed to elucidate whether evaluating the liver surface, edge, and texture by high-resolution ultrasonography is useful for predicting the occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-associated chronic liver diseases (CLDs) METHODS: The integrated fibrosis stage (a comprehensive value of scores for liver edge, surface, and texture) of 337 patients with HCV-associated CLDs was evaluated, at entry, by ultrasonography (US), as a US score. The patients were followed up prospectively (mean observation period was 16.4 months; range 2.8-36.2 months) for the occurrence of HCC by US or helical CT at 3-month intervals. A total of 140 patients received interferon therapy, and the occurrence of HCC was compared between those with and without interferon therapy RESULTS: The annual incidence of HCC was 1.1, 5.5, and 10.2% in low, middle, and high US score groups, respectively. Univariate analysis showed that age, serum levels of total bilirubin, alpha-fetoprotein (AFP), platelet count, albumin, total cholesterol, and the US score were associated with HCC occurrence in the patients. A multivariate proportional hazard model revealed that only the middle and high US scores (p = 0.0922, hazard ratio 4.006, 95% CI 0.796-20.153 and p = 0.008, hazard ratio 7.991, 95% CI 1.721-37.10, respectively) and elevated AFP (p = 0.031, hazard ratio 2.774, CI 1.097-7.014) were independently associated with HCC occurrence. Our US scoring based on evaluation of the liver surface, edge, and texture was clearly and strongly associated with the occurrence of HCC in patients with HCV-associated CLDs, and with the higher occurrence rate of HCC in patients with higher US scores CONCLUSION: Thus, US is a good tool for evaluating the fibrosis stage of the liver, and may therefore be useful in designing an optimum follow-up interval for each patient with HCV-associated CLD. PMID- 27278334 TI - Attempt to quantify uterine involution using acoustic radiation force impulse before and after placental delivery. AB - PURPOSE: The aim of the present study was to investigate whether baseline stiffness of the uterine corpus and cervix accurately estimated by acoustic radiation force impulse (AFRI) elastography changed after placental delivery. METHODS: Eleven patients with normal vaginal delivery underwent ARFI elastography before, immediately after, and 1 and 2 h after placental delivery, and the shear wave velocity was measured to determine the stiffness. Each measurement was performed in triplicate to obtain a mean +/- SD. RESULTS: The shear wave velocity of the uterine corpus before, immediately after, and 1 and 2 h after placental delivery was 1.81 +/- 0.60, 3.04 +/- 0.76, 3.12 +/- 0.95, and 2.72 +/- 0.81 m/s, respectively, and the shear wave velocity of the uterine cervix was 1.35 +/- 0.45, 1.87 +/- 0.57, 1.68 +/- 0.59, and 1.70 +/- 0.5 m/s, respectively. The stiffness of the uterine corpus significantly changed over time, although that of the uterine cervix was not significantly altered. The stiffness of the uterine corpus was significantly higher immediately after and 1 and 2 h after placental delivery as compared with that before placental delivery. The uterine corpus had a significantly higher stiffness than the uterine cervix at each of the four time points examined. CONCLUSION: ARFI elastography may be useful to assess uterine involution using the shear wave velocity. PMID- 27278335 TI - A sub-centimeter HCC with bright loop appearance diagnosed by contrast-enhanced ultrasonography. AB - Detection of a hepatocellular carcinoma (HCC) in the early stage is critical, as clinical stage influences treatment selection and patient prognosis. Carcinogenetic development of an HCC is a multi-step process, and a differential diagnosis between a dysplastic nodule and a well-differentiated HCC is often difficult. A bright loop appearance is a significant finding that indicates disappearance of fatty deposition in the central area of the nodule during the progression toward HCC, however such a finding is rare in cases of sub-centimeter sized HCCs. We encountered a case of HCC that developed a bright loop appearance on ultrasound (US) without enlargement approximately 2 years after diagnosis as a dysplastic nodule. Moreover, the hypoechoic area in the center of the nodule showed an HCC pattern in contrast enhanced US with SonazoidTM. Vascularity in the nodule could not be observed on dynamic contrast-enhanced CT or Gd-EOB-DTPA enhanced MRI. When a change in the intranodular echo pattern is observed in sub centimeter-sized nodules, examination of intranodular vascularity by contrast enhanced US is important to evaluate borderline lesions. PMID- 27278336 TI - A case of mediastinal lymphangioma: endosonographic appearance. AB - Mediastinal lymphangioma is a rare, benign disease characterized by an abnormal proliferation of lymphatic vessels. Although a definitive diagnosis can be best made by surgical resection, computed tomography (CT) and magnetic resonance imaging (MRI) can be used as radiological methods to diagnose a pulmonary lymphangioma preoperatively. Endoscopic ultrasonography is a new method for visualizing pathological changes in the mediastum and may be used for preoperative diagnosis of a pulmonary lymphangioma, which is a rare example of a mediastinal disease. PMID- 27278337 TI - A large meconium pseudocyst that developed into the generalized type during the antepartum period. AB - A fetal intraabdominal cystic mass, measuring 6 cm, was detected at 30 weeks of gestation in a 27-year-old gravida 2 para 1 woman. At 33 weeks of gestation, the cyst disappeared. Ultrasonography showed fetal bowel dilatation, polyhydramnios, and intraabdominal calcifications. Fetal meconium peritonitis was diagnosed prenatally. Because the fetal ileus became worse, a cesarean section was performed at 35 weeks of gestation; a female infant weighing 2,131 g with an Apgar score of 8 was delivered. Six hours after birth, the neonate received an ileostomy. The bowel was reanastomosed 42 days after the initial operation. On postoperative pathology, a meconium pseudocyst was diagnosed. To our knowledge, this is the first report of a large fetal meconium pseudocyst that developed into the generalized type in the uterus during the preterm antepartum period. PMID- 27278329 TI - The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC): IUPHAR Review 19. AB - Acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC) are both members of the ENaC/degenerin family of amiloride-sensitive Na(+) channels. ASICs act as proton sensors in the nervous system where they contribute, besides other roles, to fear behaviour, learning and pain sensation. ENaC mediates Na(+) reabsorption across epithelia of the distal kidney and colon and of the airways. ENaC is a clinically used drug target in the context of hypertension and cystic fibrosis, while ASIC is an interesting potential target. Following a brief introduction, here we will review selected aspects of ASIC and ENaC function. We discuss the origin and nature of pH changes in the brain and the involvement of ASICs in synaptic signalling. We expose how in the peripheral nervous system, ASICs cover together with other ion channels a wide pH range as proton sensors. We introduce the mechanisms of aldosterone-dependent ENaC regulation and the evidence for an aldosterone-independent control of ENaC activity, such as regulation by dietary K(+) . We then provide an overview of the regulation of ENaC by proteases, a topic of increasing interest over the past few years. In spite of the profound differences in the physiological and pathological roles of ASICs and ENaC, these channels share many basic functional and structural properties. It is likely that further research will identify physiological contexts in which ASICs and ENaC have similar or overlapping roles. PMID- 27278338 TI - A case of vasa previa diagnosed prenatally, and review of the literature. AB - The perinatal mortality rate of vasa previa is high if it is not prenatally diagnosed. In this report, a case of vasa previa diagnosed prenatally is presented. Antepartum hemorrhage at 24 weeks of gestation prompted a close investigation of the uterine cervix, internal os, and placenta. We detected a low lying bilobed placenta with umbilical cord insertion in the lower uterine segment. Furthermore, one of the connecting vessels of the bilobed placenta passed directly above the internal os. Vasa previa was suspected and confirmed with color Doppler and MRI. The fetus was delivered uneventfully by planned Cesarean section at 38 weeks of gestation. It should be considered that placenta previa (including low-lying placenta), bilobed placenta, and umbilical cord insertion in the lower uterine segment are associated with high risk of vasa previa. Ultrasound screening for cord insertion and placenta around the internal os enables efficient and certain detection of vasa previa. PMID- 27278339 TI - A case of perforated multiple gastric duplication cysts with five-layered appearance on ultrasonography. AB - A case of perforated multiple gastric duplication cysts is presented. One of the gastric duplication cysts without perforation was seen on ultrasonography (US) with the following specific findings of gastric duplication cysts: a five-layered appearance, fold-like structures in the wall, and blood supply from the gastroepiploic artery. Other cysts with perforation presented with irregular and thin walls with a lack of the "double-wall sign" on US. These characteristic findings may be specific to perforated multiple gastric duplication cysts. PMID- 27278340 TI - Erratum to: A case of perforated multiple gastric duplication cysts with five layered appearance on ultrasonography. PMID- 27278341 TI - A case of quadricuspid aortic valve diagnosed by three-dimensional transesophageal echocardiography and multidetector computed tomography. PMID- 27278342 TI - Prenatal ultrasonographic findings of large pseudocysts and edema of the umbilical cord. PMID- 27278343 TI - Modelling of Brain Deformation After Decompressive Craniectomy. AB - Hyperelastic finite element models, with either an idealized cylindrical geometry or with realistic craniectomy geometries, were used to explore clinical issues relating to decompressive craniectomy. The potential damage in the brain tissue was estimated by calculating the volume of material exceeding a critical shear strain. Results from the idealized model showed how the potentially damaged volume of brain tissue increased with an increasing volume of brain tissue herniating from the skull cavity and with a reduction in craniectomy area. For a given herniated volume, there was a critical craniectomy diameter where the volume exceeding a critical shear strain fell to zero. The effects of details at the craniectomy edge, specifically a fillet radius and a chamfer on the bone margin, were found to be relatively slight, assuming that the dura is retained to provide effective protection. The location in the brain associated with volume expansion and details of the material modeling were found to have a relatively modest effect on the predicted damage volume. The volume of highly sheared material in the realistic models of the craniectomy varied roughly in line with differences in the craniectomy area. PMID- 27278344 TI - Reduced-Dimension Modeling Approach for Simulating Recruitment/De-recruitment Dynamics in the Lung. AB - Acute respiratory distress syndrome is a pulmonary disease that requires the use of mechanical ventilation for patient recovery. However, this can lead to development of ventilator-induced lung injury caused by the over-distension of alveolar tissue and by the repetitive closure (de-recruitment) and reopening (recruitment) of airways. In this study, we developed a multi-scale model of the lung from a reduced-dimension approach to investigate the dynamics of ventilation in the lung during airway collapse and reopening. The model consisted of an asymmetric network geometry with 16 generations of liquid-lined airways with airflow driven by a variable pleural pressure. During the respiratory cycle changes in airway radii and film thickness yield the formation of liquid plugs that propagate and rupture throughout the airway network. Simulations were conducted with constant surface tension values [Formula: see text] dyn/cm. It was observed that the time onset of plug creation and rupture depended on the surface tension, as well as the plug aggregation/splitting behavior at bifurcations. Additionally, the plug propagation behavior was significantly influenced by presence of plugs in adjacent airways (i.e. parent and daughters) that affected the driving pressure distribution locally at bifurcations and resulted in complex aggregation and splitting behavior. This model provides an approach that has the ability to simulate normal and pathophysiological lung conditions with the potential to be used in personalized clinical medicine. PMID- 27278345 TI - Genetic characterization and founder effect analysis of recently introduced Salers cattle breed population. AB - Salers are a native French breed used for beef and dairy production that has expanded to all the continents. The Salers breed was introduced to the north of Spain in 1985 with only 15 individuals from France and has successfully increased to over 20 000 animals. Although over time new animals have been imported from France for breeding, it is possible that the limiting number of founder animals could have resulted in a reduction of the genetic diversity found in Spanish Salers. Thus, the purpose of the present study has been to characterize the genetic diversity of Salers breed in Spain and evaluate a possible founder effect due to reduced number of the first reproducers. A total of 403 individuals from 12 Salers herds were analyzed using 12 microsatellite markers and compared with phylogenetically and geographically close related Blonde d'Aquitaine, Limousin and Charolais French breeds but also other 16 European breeds. Microsatellites in Salers were polymorphic, with a mean allelic richness of 5.129 and an expected heterozygosity of 0.621 across loci (0.576 to 0.736 among all breeds). Average observed heterozygosity was 0.618. All the loci fit the Hardy-Weinberg (HW) equilibrium except TGLA227 locus due to a significant deficit of heterozygotes in only one of the herds, probably attributable to a sampling effect. When all loci were combined, Salers inbreeding coefficient did not differ statistically from 0 (F IS=0.005), indicating not significant excess or deficit of heterozygotes (P=0.309). Based in allelic distribution, Salers revealed a frequency of 0.488 in BM2113-131 and 0.064 in BM2113-143 diagnostic alleles, which are specific to the African zebu. These zebu alleles are also found in some French breeds, supported by STR data previously postulated hypothesis of a migration route through Mediterranean route by which North African cattle may have left a genetic signature in southern Europe. Phylogenetic tree and population structure analyses could unambiguously differentiate Salers cattle from the other populations and 10% of the total genetic variability could be attributed to differences among breeds (mean R ST=0.105; P<0.01). Mutation-drift equilibrium tests (sign test and Wilcoxon's sign rank test) were in correspondence to the absence of founder effect when Bonferroni was applied. Gene diversity previously reported in French Salers was comparable with the observed in our population. Thus, high genetic diversity in Spanish Salers highlights the resources of this population, which looks toward future breeding and selection programs. PMID- 27278346 TI - High E/e' disrupts the rapid lowering of blood glucose in response to exercise training. AB - BACKGROUND: No relationship between the ratio of peak early velocity of left ventricular inflow to peak systolic longitudinal velocity of the mitral annulus velocity (E/e') and insulin resistance has yet been shown in patients with cardiac disease. We hypothesized that patients with high E/e' values would tend not to show the rapid blood glucose-lowering in response to exercise training characteristic of impaired glucose tolerance (IGT) or diabetes mellitus (DM) patients. METHODS: The subjects were continuous IGT/DM patients (n = 27) participating in cardiac rehabilitation. All patients' E/e' values were measured by echocardiography. The patients' blood glucose levels (mg/dl) were measured just before (pre-BS) and after (post-BS) exercise training. Post-BS was subtracted from pre-BS to obtain DeltaBS, and the relationship between E/e' and DeltaBS was investigated. RESULTS: E/e' correlated negatively with DeltaBS. Moreover, E/e' was a significant predictor of DeltaBS and as such was independent of hemoglobin A1c (HbA1c), pre-BS, and presence of atrial fibrillation on multivariate analysis. CONCLUSIONS: Patients with high E/e', indicating high left ventricular filling pressure, were unlikely to exhibit the rapid glucose-lowering response. PMID- 27278347 TI - Comparison of the effects of angiotensin II receptor antagonist monotherapy and combination therapy with a diuretic on cardiac function in spontaneously hypertensive rats. AB - OBJECTIVE: Losartan, an angiotensin II receptor blocker (ARB), has been reported to promote sodium excretion and show an enhanced antihypertensive effect when used in combination with hydrochlorothiazide (HCTZ). We investigated the effects of losartan monotherapy and combination therapy together with HCTZ on cardiac function in hypertensive rats using echocardiography. METHODS: Spontaneously hypertensive rats (n = 21) fed on high-salt diet (8 % NaCl) for 13 weeks were randomly assigned to rats without medication (HS, n = 7), those medicated with ARB (ARB, losartan 30 mg/kg/day, n = 8), and those with ARB and HCTZ (ARB + HCTZ, losartan 30 mg/kg/day + HCTZ 10 mg/kg/day, n = 6). Blood pressure measurements and echocardiography were performed at 13, 17, and 29 weeks of age. After the end of the protocol, the proportion of cardiac muscle fibrosis was measured histologically. RESULTS: In the HS group, blood pressure and left ventricular mass/body weight (LV mass/BW) increased, and % fractional shortening (%FS) and early diastolic mitral annular velocity (e') decreased significantly with age. In the ARB group, although blood pressure and %FS were maintained, LV mass/BW increased with age as in the HS group, and e' decreased. In the ARB + HCTZ group, blood pressure decreased and LV mass/BW, %FS, and e' were maintained. The progression of myocardial fibrosis was clearly prevented in rats treated with ARB. CONCLUSION: ARB was shown to inhibit systolic disorder and myocardial fibrosis in hypertensive rats. Combination therapy proved to be more effective than monotherapy and is also effective in inhibiting diastolic disorders. PMID- 27278348 TI - Multiple coronary artery fistulae with biventricular hypertrophy. AB - Here, we report a case of multiple coronary artery fistulae with biventricular hypertrophy. The initial diagnosis of multiple coronary artery fistulae, draining into the left as well as the right ventricle, was made by standard transthoracic 2-dimensional and Doppler echocardiography. Later, multiple coronary fistulae communicating with the left ventricle through persistent sinusoids were diagnosed by coronary angiography. PMID- 27278349 TI - Right- and left-sided carcinoid heart disease without intracardiac shunting. AB - We present a case of a 54-year-old man with carcinoid heart disease and mitral valve involvement. He had hepatic carcinoid with an extremely elevated urinary excretion of 5-hydroxyindole acetic acid and was referred to our division for shortness of breath and leg edema. Transthoracic echocardiography showed the thickened and retracted tricuspid valve leaflets and severe tricuspid regurgitation. Moderate mitral regurgitation was observed, with the involvement of mitral valve leaflets. A patent foramen ovale was not detected on transesophageal echocardiography. The extremely high concentration of circulating serotonin and/or other vasoactive substances may have contributed to left- as well as right-sided carcinoid heart disease. PMID- 27278350 TI - A rare case of impending paradoxical embolism with a complex patent foramen ovale. AB - A 68-year-old woman, who presented with pulmonary embolism, was diagnosed as having an impending paradoxical thromboembolism by transthoracic and transesophageal echocardiography, which revealed an entrapped thrombus in the atrial septum. The patient underwent surgery for thromboembolectomy. A patent foramen ovale (PFO) appeared as a tunnel with three openings into the left atrium; one opening located close to the antero-superior left atrial wall and two small atrial septal defects of a septum primum. A thrombus was trapped at two small atrial septal defects. This was a rare case of impending paradoxical embolism with complex morphology of PFO. PMID- 27278351 TI - Three-dimensional echocardiography in the diagnosis of pacemaker lead perforation. AB - Recently, due to increases in the number of cardiac device implantations, especially implantable cardioverter-defibrillators and cardiac resynchronization therapy, device complications have been experienced more frequently. Myocardial perforation of an implanted lead is one of the most severe complications. We report a case of ventricular lead perforation clearly visualized by 3-dimensional echocardiography, which was not identified by 2-dimensional echocardiography. PMID- 27278352 TI - Systolic anterior motion of the mitral valve and severe mitral regurgitation immediately after transcatheter aortic valve replacement. AB - We report a high-risk patient with severe symptomatic aortic stenosis who showed systolic anterior motion of the mitral valve (SAM) and severe mitral regurgitation immediately after transcatheter aortic valve replacement (TAVR). The patient did not have either SAM or mitral regurgitation, but showed significant septal hypertrophy on preoperative transthoracic echocardiography which could be associated with the occurrence of SAM. Caution should be exercised in patients with significant interventricular septal hypertrophy before TAVR. PMID- 27278353 TI - Double-chambered right ventricle presenting significant outflow tract obstruction only in the right decubitus position. AB - A 75-year-old man was referred to our echocardiography laboratory for presurgical evaluation. His past history included ventricular septal defect closure. He reported chest discomfort in the right decubitus position. Two-dimensional and Doppler echocardiography revealed an anomalous muscle bundle with accelerated blood flow in the right ventricle. The peak flow velocity of the flow increased from 1.4 m/s in the left decubitus position to 2.9 m/s in the right decubitus position. Double-chamber right ventricle with intermittent mid-ventricular obstruction during the right decubitus position was confirmed by transesophageal echocardiography. PMID- 27278354 TI - A case of aortic bicuspid valve with thrombus formation without severe stenosis and calcification. AB - We encountered a patient with a history of juvenile cerebral infarction with an unknown cause in whom a mass adhering to the aortic valve (AV) surface was observed on echocardiography performed upon the development of heart failure. Mild AV stenosis (AS) with moderate regurgitation was noted, and valve repair was applied. It was found during surgery that the AV was a bicuspid valve (BAV) without calcification, and the mass was an organized thrombus. Thrombus formation on the AV with severe AS in BAV has been reported, but the organic lesion in the AV was mild in this patient. PMID- 27278355 TI - Aortic regurgitation caused by fibrous strand rupture in a fenestrated aortic valve. AB - Fibrous strand rupture in a fenestrated aortic valve can cause acute severe aortic regurgitation. We report the case of a 56-year-old woman with severe aortic regurgitation. Transesophageal echocardiography showed an abnormal fibrous strand echo on the prolapsed left coronary cusp (LCC). The operative finding revealed one ruptured fibrous strand attached to the LCC at the commissure between the left and noncoronary cusps. Pathologic examination of the aortic valve revealed myxomatous degeneration. PMID- 27278356 TI - Acute aortic dissection flap prolapsing into the left ventricle on transthoracic echocardiography. PMID- 27278357 TI - A rare case of cardiac myxoma from the left atrial appendage presenting with acute myocardial infarction. PMID- 27278358 TI - LTP-1, a novel antimitotic agent and Stat3 inhibitor, inhibits human pancreatic carcinomas in vitro and in vivo. AB - Pancreatic cancer is the leading cause of cancer death worldwide with a poor survival rate. The objective of this study was to determine the mechanism of action of a novel antimitotic and Stat3 inhibitor, LTP-1, on human pancreatic cancer in vitro and in vivo. We found that LTP-1 inhibited pancreatic cancer cell growth and viability with significant G2/M arrest and disruption of microtubule dynamics. LTP-1 also caused G2/M arrest-independent Stat3 dephosphorylation along with ERK activation, which indicated the possible dual function of LTP-1. Long term treatment of LTP-1 also induced polyploidy, activated caspases, induced subG1 cell population, and therefore, triggered pancreatic cancer cell apoptosis. Finally, we used an in vivo xenograft model to demonstrate that LTP-1 suppressed the growth of pancreatic adenocarcinoma. In summary, our data suggest that LTP-1 may alter microtubule dynamics, which ultimately causes polyploidy and apoptosis, thereby inhibiting pancreatic cancer growth in vitro and in vivo. This study provides evidence that LTP-1 could be a potential therapeutic agent for further development of pancreatic cancer treatment. PMID- 27278359 TI - Decision-making without a brain: how an amoeboid organism solves the two-armed bandit. AB - Several recent studies hint at shared patterns in decision-making between taxonomically distant organisms, yet few studies demonstrate and dissect mechanisms of decision-making in simpler organisms. We examine decision-making in the unicellular slime mould Physarum polycephalum using a classical decision problem adapted from human and animal decision-making studies: the two-armed bandit problem. This problem has previously only been used to study organisms with brains, yet here we demonstrate that a brainless unicellular organism compares the relative qualities of multiple options, integrates over repeated samplings to perform well in random environments, and combines information on reward frequency and magnitude in order to make correct and adaptive decisions. We extend our inquiry by using Bayesian model selection to determine the most likely algorithm used by the cell when making decisions. We deduce that this algorithm centres around a tendency to exploit environments in proportion to their reward experienced through past sampling. The algorithm is intermediate in computational complexity between simple, reactionary heuristics and calculation intensive optimal performance algorithms, yet it has very good relative performance. Our study provides insight into ancestral mechanisms of decision making and suggests that fundamental principles of decision-making, information processing and even cognition are shared among diverse biological systems. PMID- 27278360 TI - Effects of El Nino-driven changes in wind patterns on North Pacific albatrosses. AB - Changes to patterns of wind and ocean currents are tightly linked to climate change and have important implications for cost of travel and energy budgets in marine vertebrates. We evaluated how El Nino-Southern Oscillation (ENSO)-driven wind patterns affected breeding Laysan and black-footed albatross across a decade of study. Owing to latitudinal variation in wind patterns, wind speed differed between habitat used during incubation and brooding; during La Nina conditions, wind speeds were lower in incubating Laysan (though not black-footed) albatross habitat, but higher in habitats used by brooding albatrosses. Incubating Laysan albatrosses benefited from increased wind speeds during El Nino conditions, showing increased travel speeds and mass gained during foraging trips. However, brooding albatrosses did not benefit from stronger winds during La Nina conditions, instead experiencing stronger cumulative headwinds and a smaller proportion of trips in tailwinds. Increased travel costs during brooding may contribute to the lower reproductive success observed in La Nina conditions. Furthermore, benefits of stronger winds in incubating habitat may explain the higher reproductive success of Laysan albatross during El Nino conditions. Our findings highlight the importance of considering habitat accessibility and cost of travel when evaluating the impacts of climate-driven habitat change on marine predators. PMID- 27278362 TI - Open water camouflage via 'leaky' light guides in the midwater squid Galiteuthis. AB - Galiteuthis, a midwater squid, has photophores on the ventral surfaces of its eyes. These photophores emit bioluminescence to counter-illuminate the shadows cast by the eyes in downwelling sunlight, thereby hiding the eyes from upward looking predators. The photophores consist of laminated fibre-like cells with semi-coaxial protein-dense layers around axial cytoplasm. These cells have been suggested to function as light guides: bioluminescence is an isotropic process used to hide in an anisotropic light environment, so any emission must be reshaped to be effective. We found a wide variation in cross-sectional geometries of photophore cells; some were more efficient at light guiding than others. We used a set of optical models to place these photophores in the context of the radiance where Galiteuthis lives and discovered a possible adaptive reason for this variation. In Galiteuthis's horizontal and vertical range, ocean radiance is also quite variable. For complete camouflage, photophores must reproduce this variation in radiance using an isotropic source. Our models show that variation in the geometry of the photophore light guides reproduces the predicted variation in ocean radiance experienced by this species. By selectively activating geometrically distinct populations of photophore cells, the animal may reproduce the angular distribution of light at all positions in its habitat. PMID- 27278361 TI - Control at stability's edge minimizes energetic costs: expert stick balancing. AB - Stick balancing on the fingertip is a complex voluntary motor task that requires the stabilization of an unstable system. For seated expert stick balancers, the time delay is 0.23 s, the shortest stick that can be balanced for 240 s is 0.32 m and there is a [Formula: see text] degrees dead zone for the estimation of the vertical displacement angle in the saggital plane. These observations motivate a switching-type, pendulum-cart model for balance control which uses an internal model to compensate for the time delay by predicting the sensory consequences of the stick's movements. Numerical simulations using the semi-discretization method suggest that the feedback gains are tuned near the edge of stability. For these choices of the feedback gains, the cost function which takes into account the position of the fingertip and the corrective forces is minimized. Thus, expert stick balancers optimize control with a combination of quick manoeuvrability and minimum energy expenditures. PMID- 27278363 TI - Periodicity, synchronization and persistence in pre-vaccination measles. AB - We investigate the relationship between periodicity, synchronization and persistence of measles through simulations of geographical spread on the British Isles. We show that the establishment of areas of biennial periodicity depends on the interplay between human mobility and local population size and that locations undergoing biennial cycles tend to be, on average, synchronized in phase. We show however that occurrences of opposition of phase are actually quite common and correspond to stable dynamics. We also show that persistence is strictly related to circulation of the disease in the highly populated area of London and that this ensures survival of the disease even when human mobility drops to extremely low levels. PMID- 27278365 TI - Modelling the relation between income and commuting distance. AB - We discuss the distribution of commuting distances and its relation to income. Using data from Denmark, the UK and the USA, we show that the commuting distance is (i) broadly distributed with a slow decaying tail that can be fitted by a power law with exponent gamma ~ 3 and (ii) an average growing slowly as a power law with an exponent less than one that depends on the country considered. The classical theory for job search is based on the idea that workers evaluate the wage of potential jobs as they arrive sequentially through time, and extending this model with space, we obtain predictions that are strongly contradicted by our empirical findings. We propose an alternative model that is based on the idea that workers evaluate potential jobs based on a quality aspect and that workers search for jobs sequentially across space. We also assume that the density of potential jobs depends on the skills of the worker and decreases with the wage. The predicted distribution of commuting distances decays as 1/r(3) and is independent of the distribution of the quality of jobs. We find our alternative model to be in agreement with our data. This type of approach opens new perspectives for the modelling of mobility. PMID- 27278364 TI - Understanding the within-host dynamics of influenza A virus: from theory to clinical implications. AB - Mathematical models have provided important insights into acute viral dynamics within individual patients. In this paper, we study the simplest target cell limited models to investigate the within-host dynamics of influenza A virus infection in humans. Despite the biological simplicity of the models, we show how these can be used to understand the severity of the infection and the key attributes of possible immunotherapy and antiviral drugs for the treatment of infection at different times post infection. Through an analytic approach, we derive and estimate simple summary biological quantities that can provide novel insights into the infection dynamics and the definition of clinical endpoints. We focus on nine quantities, including the area under the viral load curve, peak viral load, the time to peak viral load and the level of cell death due to infection. Using Markov chain Monte Carlo methods, we fitted the models to data collected from 12 untreated volunteers who participated in two clinical studies that tested the antiviral drugs oseltamivir and zanamivir. Based on the results, we also discuss various difficulties in deriving precise estimates of the parameters, even in the very simple models considered, when experimental data are limited to viral load measures and/or there is a limited number of viral load measurements post infection. PMID- 27278366 TI - Enhanced identification of synergistic and antagonistic emergent interactions among three or more drugs. AB - Interactions among drugs play a critical role in the killing efficacy of multi drug treatments. Recent advances in theory and experiment for three-drug interactions enable the search for emergent interactions-ones not predictable from pairwise interactions. Previous work has shown it is easier to detect synergies and antagonisms among pairwise interactions when a rescaling method is applied to the interaction metric. However, no study has carefully examined whether new types of normalization might be needed for emergence. Here, we propose several rescaling methods for enhancing the classification of the higher order drug interactions based on our conceptual framework. To choose the rescaling that best separates synergism, antagonism and additivity, we conducted bacterial growth experiments in the presence of single, pairwise and triple-drug combinations among 14 antibiotics. We found one of our rescaling methods is far better at distinguishing synergistic and antagonistic emergent interactions than any of the other methods. Using our new method, we find around 50% of emergent interactions are additive, much less than previous reports of greater than 90% additivity. We conclude that higher order emergent interactions are much more common than previously believed, and we argue these findings for drugs suggest that appropriate rescaling is crucial to infer higher order interactions. PMID- 27278367 TI - FGFR Family Members Protein Expression as Prognostic Markers in Oral Cavity and Oropharyngeal Squamous Cell Carcinoma. AB - INTRODUCTION: Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort. METHODS: Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation. RESULTS: FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC (p > 0.05). CONCLUSION: FGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients. PMID- 27278368 TI - Categorization does not promote symmetry in Guinea baboons (Papio papio). AB - Humans have the capacity to use stimuli interchangeably by forming equivalence classes, and this ability seems to be supported by our language system. According to Sidman and Tailby (Conditional discrimination vs. matching to sample: an expansion of the testing paradigm. J Exp Anal Behav 37:5-22, 1982), the formation of equivalence classes require that three relations are derived among the class members, and past experiments have shown that one of these relations, i.e., symmetry, corresponding to the ability to reverse a relation (if A -> B, then B > A), is extremely difficult to obtain in non-human animals. Because language development and the ability to form equivalence classes both co-occur in children with an increased ability to form categories, the current study tested the idea that category learning might promote symmetry in a nonhuman primate species. In Experiment 1, twelve Guinea baboons (Papio papio) were trained to associate 60 pictures of bears and 60 pictures of cars to two category labels, before being tested in symmetry trials. In Experiment 2, symmetry was trained and tested by reversing the association order between labels and pictures, using a new set of stimuli. In both experiments, the baboons successfully demonstrated category discrimination, but had only a weak (though significant) tendency to respond in accordance with symmetry during test trials. Altogether, our results confirm that symmetry is inherently difficult in non-human animals. We discuss possible explanations for such a limitation and give reasons for thinking that the effects of categorization on symmetry should be further investigated. PMID- 27278371 TI - Sustained release of isoniazid from polylactide microspheres prepared using solid/oil drug loading method for tuberculosis treatment. AB - Polylactide (PLA) microspheres were prepared using the solid-in-oil (S/O) spray drying method to achieve the sustained release of a hydrophilic drug for the treatment of tuberculosis, via intratracheal instillation. Isoniazid (IN), a low molecular-weight hydrophilic drug, was used as a model drug. The effects of various sizes of micronized IN powder, different drug/polymer ratios, spray drying process parameters, and drug-release characteristics were studied to optimize the manufacturing parameters. A high entrapment efficiency (87.3%) was obtained using this method; furthermore, the microspheres were spherical and smooth. They were individually and homogenously distributed, with a mean diameter of 5.6 MUm; furthermore, they showed a satisfactory extended sustained-release phase. After administration of the microspheres to rats, pulmonary drug concentrations were maintained at a relatively stable level for up to 4 weeks. PMID- 27278372 TI - A single mutation in the PBC loop of VP2 is involved in the in vitro replication of infectious bursal disease virus. AB - To test whether amino acid mutations in the PBC and PHI loops of VP2 are involved in the replication and virulence of infectious bursal disease virus (IBDV), a pair of viruses, namely the moderately virulent IBDV (rGx-F9VP2) and the attenuated strain (rGt), were used. Residue mutations A222P (PBC) and S330R (PHI), selected by sequence comparison, were introduced individually into rGx F9VP2 by using a reverse genetics system. In addition, the reverse mutation of either P222A or R330S was introduced into rGt. The four modified viruses were then rescued and evaluated in vitro (CEF cells) and in vivo (SPF chickens). Results showed that A222P elevated the replication efficiency of rGx-F9VP2 while P222A reduced that of rGt in CEF cells. A mutation at residue 330 did not alter IBDV replication. In addition, animal experiments showed that a single mutation at either residue 222 or 330 did not significantly influence the virulence of IBDV. In conclusion, residue 222 in PBC of VP2 is involved in the replication efficiency of IBDV in vitro but does not affect its virulence in vivo, further facilitating our understanding of the gene-function of IBDV. PMID- 27278369 TI - Obstructive Sleep Apnoea and Hypertension: the Role of the Central Nervous System. AB - PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is associated with both nocturnal and daytime hypertensions which increase cardiovascular morbidity and mortality. It is thought that the repeated episodes of hypoxia and hypercapnia during nocturnal airway obstructions that characterise OSA result in increased sympathetic drive that persists during wakefulness. Although the underlying mechanisms responsible for this hypertension remain to be elucidated, several neural and humoral mechanisms have been proposed and recent evidence suggesting changes in the central nervous system may play a significant role. The purpose of this review is to explore recent evidence of central changes associated with elevated sympathetic drive in individuals with OSA. RECENT FINDINGS: Recent human brain imaging investigations and, in particular, combined microneurography recording of resting sympathetic activity with high-resolution functional magnetic resonance imaging have provided some important insights into changes in brain function and anatomy associated with resting sympathetic activity. Functional and anatomical changes occur in OSA, including in regions of the brainstem circuitry known to be responsible for setting resting sympathetic activity. Furthermore, these changes are reversed following continuous positive airway treatment in concert with reductions in resting sympathetic drive. These resent findings suggest that the central changes may contribute significantly to the hypertension associated with OSA. PMID- 27278373 TI - Rhegmatogenous retinal detachment following intravitreal ocriplasmin. AB - PURPOSE: To describe the characteristics and outcomes of patients presenting with rhegmatogenous retinal detachment (RRD) after ocriplasmin (OCP) injection. METHODS: Retrospective, multi-centre, observational case series with case note review. RESULTS: Eight patients with symptomatic vitreomacular traction (six with concomitant macular hole) were diagnosed with RRD after a median of 16 days (range 3-131 days) post-OCP injection. Presentation was within 3 weeks of the OCP injection in six of the cases. Five patients presented with symptoms post-OCP, and three were diagnosed asymptomatically on planned visits. Seven cases were phakic, one had high myopia (>8 dioptres), and two cases had lattice degeneration. Following RRD surgery, hole closure was achieved in 5/6 MH cases. The final median BCVA at 7 months was 20/80 (range 20/40-20/1200) similar to the baseline BCVA 20/80, with four patients gaining >=1 line of vision compared to baseline but three losing >=3 lines. CONCLUSIONS: RRD is a non-negligible risk associated with intravitreal OCP, and it should be used with caution in eyes with high myopia and peripheral retinal pathology predisposing to RRD. Detailed peripheral retinal examination is recommended pre- and postoperatively at all visits. Patients should be advised to seek attention if symptoms recur after initial presentation. PMID- 27278374 TI - Vision loss under silicone oil tamponade. AB - PURPOSE: We aimed to investigate frequency, time course and pathophysiology of vision loss in eyes with macula-on rhegmatogenous retinal detachment operated with vitrectomy and silicone oil tamponade. PATIENTS AND METHODS: Fifteen eyes of 15 patients who had been operated with 5,000 centistoke silicone oil between 2006 and 2014 were included in a retrospective case series. Examinations included logMAR best corrected visual acuity (BCVA), visual field testing (VF), spectral domain optical coherence tomography (OCT), electrophysiology, and fluorescein angiography. RESULTS: Vision loss was seen in eight (53 %) eyes of 15 patients with symptomatic central scotoma, which was confirmed by VF (5/6). Preoperative median BCVA of these patients was 0.15 (0.5 to 0), prior to oil removal 0.7 (1.0 to 0.5), and 6 weeks post oil removal 1.0 (1.5 to 0.2). BCVA recovered in five patients to a median of 0.15 (0.5 to 0.1), and it remained 1.0 in three (20 %) out of 15 eyes. OCT revealed significant thinning of the foveal and parafoveal combined nerve fiber, ganglion cell and inner plexiform layers in affected eyes (mean 58.3 MUm +/-13, horizontal scan through fovea, 500 MUm radius) compared to their healthy fellow eyes (mean 84.5 MUm +/-12.3; p < 0.01, n = 6 patients, 12 eyes) and compared to eyes with no vision loss under silicone oil. CONCLUSIONS: We find persisting vision loss in three out of 15 patients treated for macula-on rhegmatogenous retinal detachment with silicone oil tamponade. Thinning of inner retinal layers possibly evoked by silicone oil tamponade might be a pathophysiological explanation for vision loss in these patients. PMID- 27278375 TI - [Fifth symposium on renal cell cancer]. PMID- 27278376 TI - Partial replacement of left hemidiaphragm in dogs by either cryopreserved or decellularized heterograft patch. AB - OBJECTIVES: Large diaphragmatic defects are still a challenging issue for reconstruction using either synthetic prosthesis or bioprosthesis. To evaluate the possibility of using diaphragm allograft as a natural bioprosthesis in humans, we conducted a two-group study and compared cryopreserved and decellularized diaphragmatic heterograft patched in a canine model. METHODS: At the end of organ harvesting from a human donor, the left hemidiaphragm was taken to the laboratory in phosphate-buffered saline solution. The next step was freezing the grafts at -80 degrees C, and preserving them for up to 2 months in Group 1. It was subjected to a detergent-enzymatic method (containing sodium deoxycholate/DNase lavations) of decellularization for 25 cycles in Group 2. Through left thoracotomy in the eighth intercostal space, cryopreserved patches in six dogs and decellularized patches in five dogs replaced the diaphragm. During the follow-up, sonography was done in all animals, but three and two dogs in Group 1 and 2 underwent computed tomography (CT) scan, respectively. The animals were euthanized after 6 months. RESULTS: There was no mortality. Sonography showed only motion impairment of the patches in all cases. In Group 1, CT scan showed mild atelectasis and scattered infiltration in the left lower lobe, fibrotic bands and minimal fluid collection under the diaphragm. In Group 2, CT scan showed scattered fibrotic bands and mild to moderate elevation of the left hemidiaphragm. There was no evidence of gross disruption and complete healing of the suture line. Necropsy in both groups showed patches were completely replaced with a dense fibrous tissue. In Group 1, focal calcification was noticeable in every case and foreign body-type granulomas were clearly seen all over the grafted tissue. Histology in Group 2 animals showed less inflammatory cell infiltration and scattered foreign body granulomas in comparison with the cryopreserved patch graft. CONCLUSIONS: The gross healing process in the decellularized heterograft is similar to the cryopreserved diaphragm but with fewer inflammatory cells and foreign body granulomas on histology. Both of them can be used instead of bioprostheses with regard to the fact that the decellularized patch technique is more complex and expensive. It is recommended to compare them with commercial bioprostheses. PMID- 27278378 TI - Expression of Membrane-Bound Mucins and p63 in Distinguishing Mucoepidermoid Carcinoma from Papillary Cystadenoma. AB - The aim of this study was to compare the immunoexpression of epithelial mucins (MUCs) in salivary duct cysts, papillary cystadenomas, and mucoepidermoid carcinomas and to evaluate if any of these markers could be useful for differentiating between mucoepidermoid carcinoma and papillary cystadenoma. We also sought to validate the p63 expression pattern found to differentiate between mucoepidermoid carcinoma and papillary cystadenoma. Immunoexpression of MUC1, MUC2, MUC4, MUC7, and p63 was studied and quantified in 22 mucoepidermoid carcinomas, 12 papillary cystadenomas, and 3 salivary duct cysts. The immunohistochemical evaluation was collectively performed by 3 oral pathologists. Scores and trends in proportions were assessed using the nonparametric Wilcoxon Mann-Whitney rank sum test. Mucoepidermoid carcinomas, papillary cystadenomas, and salivary duct cysts demonstrated variable MUC expression patterns. All tumors were positive for p63 immunoexpression with p63 labeling in salivary duct cysts and papillary cystadenomas (15/15) limited to the basal layers of the cystic spaces, whereas in mucoepidermoid carcinomas (22/22) the p63 labeling extended throughout the suprabasal layers (p < 0.001). This study adds more confirmatory data to validate that the reactivity pattern of p63 protein can be used in distinguishing between papillary cystadenoma and low-grade mucoepidermoid carcinoma. Although positive reactivity in a tumor with MUC1 and MUC4 was inconclusive, negative reactivity suggests the diagnosis of a benign PC or SDC. PMID- 27278379 TI - Sinus of Valsalva dilates disproportionately in aortic root aneurysm with moderate to severe aortic regurgitation: quantitative assessment by transesophageal echocardiography. AB - BACKGROUND: Geometric change of the aortic valve and root in patients with aortic root aneurysm has not been well investigated. The aim of this study was to quantitatively assess the characteristics of aortic valve and root morphology in patients with aortic root aneurysm. METHODS: Ten aortic root aneurysm patients (eight males, group A) with moderate to severe aortic regurgitation and ten controls with normal aortic valves (seven males, group N) were examined by transesophageal echocardiography. We measured the diameter of the aortic annulus, sinus of Valsalva, sinotubular junction (STJ) and ascending aorta, and the length of the valve coaptation and annulus to the leaflet tip. We also measured the cusp projection area, STJ arc length, leaflet tip-Valsalva wall diameter and inter commissural diameter in each Valsalva sinus/cusp [left coronary cusp (LCC), right coronary cusp (RCC), non-coronary cusp (NCC)]. RESULT: The diameters of the sinus of Valsalva (P = 0.003), STJ (P = 0.005) and ascending aorta (P = 0.008) were more significantly enlarged in group A than in group N, and the valve coaptation length was significantly shorter in group A than in group N (3.1 +/- 1.1 vs. 4.9 +/- 1.1 mm/m(2), P = 0.007). Moreover, the annulus to leaflet tip length was significantly longer in group A than in group N (P = 0.049). There was no significant difference in the size of the LCC, RCC and NCC in group N, although there was disproportion in the size of those cusps in group A, with the largest being in RCCs. CONCLUSIONS: In patients with aortic root aneurysm, Valsalva sinuses disproportionately dilate with different size, causing the loss of coaptation. PMID- 27278377 TI - Kinetic DTI of the cervical spine: diffusivity changes in healthy subjects. AB - INTRODUCTION: The study aims to assess the influence of neck extension on water diffusivity within the cervical spinal cord. METHODS: IRB approved the study in 22 healthy volunteers. All subjects underwent anatomical MR and diffusion tensor imaging (DTI) at 1.5 T. The cervical cord was imaged in neutral (standard) position and extension. Segmental vertebral rotations were analyzed on sagittal T2-weighted images using the SpineView(r) software. Spinal cord diffusivity was measured in cross-sectional regions of interests at multiple levels (C1-C5). RESULTS: As a result of non-adapted coil geometry for spinal extension, 10 subjects had to be excluded. Image quality of the remaining 12 subjects was good without any deteriorating artifacts. Quantitative measurements of vertebral rotation angles and diffusion parameters showed good intra-rater reliability (ICC = 0.84-0.99). DTI during neck extension revealed significantly decreased fractional anisotropy (FA) and increased radial diffusivity (RD) at the C3 level and increased apparent diffusion coefficients (ADC) at the C3 and C4 levels (p < 0.01 Bonferroni corrected). The C3/C4 level corresponded to the maximal absolute change in segmental vertebral rotation between the two positions. The increase in RD correlated positively with the degree of global extension, i.e., the summed vertebral rotation angle between C1 and C5 (R = 0.77, p = 0.006). CONCLUSION: Our preliminary results suggest that DTI can quantify changes in water diffusivity during cervical spine extension. The maximal differences in segmental vertebral rotation corresponded to the levels with significant changes in diffusivity (C3/C4). Consequently, kinetic DTI measurements may open new perspectives in the assessment of neural tissue under biomechanical constraints. PMID- 27278380 TI - Assessment of atrial septal defect size and residual rim using real-time 3D transesophageal echocardiography. AB - BACKGROUND: Accurate preoperative determination of defect location and size is important for successful transcatheter closure of atrial septal defects (ASD). Real-time 3D transesophageal echocardiography (3DTEE) has the potential to delineate the shape of ASD in 3D space. METHODS: Full volume and 3D zoom datasets by 3DTEE were acquired in 17 ASD patients. Using quantitative software, maximal/minimal diameter, defect area and residual rim length were measured and compared to the standard 2D measurements. RESULTS: Real-time 3DTEE allowed delineation of the en-face view of the ASDs. The defect typically had an oval shape, and its size changed dynamically, having its minimal size at end-diastole and maximal at end-systole. A good correlation was noted between the maximal defect area by 3DTEE and 2DTEE (r = 0.93, p < 0.001). Successful delineation of rim length to the specific cardiac structure was 100% by 3DTEE and 88% by 2DTEE. There was a fair correlation of residual rim length between 3DTEE and 2DTEE (r = 0.69, p < 0.001). Eight patients underwent transcatheter closure of the ASD. Excellent correlation was noted between 3D-derived maximal defect diameter and device diameter (r = 0.97, p < 0.001). CONCLUSIONS: Real-time 3DTEE allows measurements of the temporal and spatial changes of ASD size and shape. This methodology provides detailed information on defect dynamics. PMID- 27278381 TI - A case of echocardiographic evaluation of ruptured pseudoaneurysm of the mitral aortic intervalvular fibrosa by infective endocarditis. AB - This report describes an unusual case of ruptured pseudoaneurysm (PSA) of mitral aortic intervalvular fibrosa (MAIVF) caused by infective endocarditis. The PSA ruptured into the left sinus of Valsalva in addition to the left atrium, resulting in complicated shunting among the aorta, left ventricle and left atrium, leading to refractory heart failure. The transesophageal echocardiography provided the precise information concerning the anatomical detail of the PSA, which is crucial for the surgical repair. This is the first report describing a patient with PSA of MAIVF with two rupture sites. PMID- 27278382 TI - Cor triatriatum sinister disclosed after diagnosis of acute myocardial infarction. AB - We present a case of cor triatriatum sinister diagnosed occasionally after acute anterior myocardial infarction. For management of the acute myocardial infarction (AMI), urgent reperfusion therapy was successfully performed through the left anterior descending coronary artery. Thereafter, no complication associated with AMI occurred. Cor triatriatum sinister was diagnosed and assessed later by means of several modalities. Finally, medical observation was indicated for this patient. This case illustrates the importance of awareness of this congenital disease in an adult when echocardiography shows an abnormal linear echo in the mid portion of the left atrium. PMID- 27278383 TI - Serial images of thrombi traversing the interaterial septum through a patent foramen ovale. PMID- 27278384 TI - Multiwalled carbon nanotubes enter broccoli cells enhancing growth and water uptake of plants exposed to salinity. AB - BACKGROUND: Carbon nanotubes have been shown to improve the germination and growth of some plant species, extending the applicability of the emerging nano biotechnology field to crop science. RESULTS: In this work, exploitation of commercial multiwalled carbon nanotubes (MWCNTs) in control and 100 mM NaCl treated broccoli was performed. Transmission electron microscopy demonstrated that MWCNTs can enter the cells in adult plants with higher accumulation under salt stress. Positive effect of MWCNTs on growth in NaCl-treated plants was consequence of increased water uptake, promoted by more-favourable energetic forces driving this process, and enhanced net assimilation of CO2. MWCNTs induced changes in the lipid composition, rigidity and permeability of the root plasma membranes relative to salt-stressed plants. Also, enhanced aquaporin transduction occurred, which improved water uptake and transport, alleviating the negative effects of salt stress. CONCLUSION: Our work provides new evidences about the effect of MWCNTs on plasma membrane properties of the plant cell. The positive response to MWCNTs in broccoli plants opens novel perspectives for their technological uses in new agricultural practices, especially when 1plants are exposed to saline environments. PMID- 27278386 TI - Survey nonresponse among informal caregivers: effects on the presence and magnitude of associations with caregiver burden and satisfaction. AB - BACKGROUND: Informal caregiving is becoming more relevant with current trends such as population ageing. However, little is known about nonconsent and nonresponse bias in caregiving research. We investigated nonconsent and nonresponse bias in a sample of informal caregivers who participated in the LifeLines Cohort Study, and were invited for participation in an additional caregiving study. METHODS: We compared socio-demographic characteristics, caregiver health, caregiving situation, and caregiver outcomes of nonconsent and consent caregivers, and nonresponse and response caregivers, on LifeLines data, by using Chi-square tests, Independent Sample T-tests, and Mann-Whitney tests. Furthermore, we examined the influence of nonconsent and nonresponse on the presence and magnitude of the associations between caregiver characteristics and two commonly used caregiving outcomes (caregiver burden and satisfaction). We conducted multinomial logistic regression analyses, including interaction terms with nonconsent and nonresponse. RESULTS: Within a subcohort of 8443 caregivers, aged >18 years, 5095 caregivers (60 %) gave consent for participation in the caregiving study. Within the subgroup of 2002 caregivers who received the questionnaire, 965 (48 %) responded. Caregivers who were highly involved in caregiving (i.e. high time investment, high caregiver burden), gave more commonly consent to participate, and responded more often to the questionnaire. Nonconsent and nonresponse influenced the associations between caregiver characteristics and caregiver burden for only a few characteristics, mainly indicating the level of caregiving involvement (e.g. time investment, caregiving duration). Especially for caregiver burden, these indicators were stronger for consent and response caregivers than for nonconsent and nonresponse caregivers. CONCLUSIONS: Our findings are important for caregiving research, as they emphasized that participation might not be evenly distributed among caregivers, and that the possibility of nonconsent and nonresponse bias should be considered. PMID- 27278385 TI - Direct effects of physical training on markers of bone metabolism and serum sclerostin concentrations in older adults with low bone mass. AB - BACKGROUND: Both gravitational loading and the forces generated by muscle contraction have direct effects on serum markers of bone metabolism. The object of this study was to examine the direct effects of a single session of resistance exercise or walking on biochemical markers of bone metabolism in participants with low bone mass. METHODS: A total of 150 otherwise healthy female subjects (mean age = 59.1 +/- 7.1 years) diagnosed with osteoporosis or osteopenia were randomly allocated to either a resistance exercise group (RG; n = 50), walking group (WG; n = 50), or control group (CG; n = 50). Changes in bone-specific alkaline phosphatase (BALP), carboxy-terminal cross-linked telopeptide of type I collagen (CTX), and serum sclerostin concentrations were measured before and immediately after a single exercise intervention. RESULTS: There was no significant change in BALP values in any of the groups. Sclerostin levels increased in the RG and WG, and there was significant difference between the WG and CG after the exercise intervention (P < 0.01). In contrast, the changes in CTX concentrations from baseline were significant in the RG (P < 0.01) but not in the WG (P = 0.11), and there was a significant difference between resistance exercise and walking (P < 0.01). CONCLUSIONS: In participants with low bone mass, resistance exercise influenced the serum concentrations of CTX, a marker of bone resorption, but walking did not. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16329455 ; retrospectively registered on 05/05/2016. PMID- 27278387 TI - A new method for classifying different phenotypes of kidney transplantation. AB - For end-stage renal diseases, kidney transplantation is the most efficient treatment. However, the unexpected rejection caused by inflammation usually leads to allograft failure. Thus, a systems-level characterization of inflammation factors can provide potentially diagnostic biomarkers for predicting renal allograft rejection. Serum of kidney transplant patients with different immune status were collected and classified as transplant patients with stable renal function (ST), impaired renal function with negative biopsy pathology (UNST), acute rejection (AR), and chronic rejection (CR). The expression profiles of 40 inflammatory proteins were measured by quantitative protein microarrays and reduced to a lower dimensional space by the partial least squares (PLS) model. The determined principal components (PCs) were then trained by the support vector machines (SVMs) algorithm for classifying different phenotypes of kidney transplantation. There were 30, 16, and 13 inflammation proteins that showed statistically significant differences between CR and ST, CR and AR, and CR and UNST patients. Further analysis revealed a protein-protein interaction (PPI) network among 33 inflammatory proteins and proposed a potential role of intracellular adhesion molecule-1 (ICAM-1) in CR. Based on the network analysis and protein expression information, two PCs were determined as the major contributors and trained by the PLS-SVMs method, with a promising accuracy of 77.5 % for classification of chronic rejection after kidney transplantation. For convenience, we also developed software packages of GPS-CKT (Classification phenotype of Kidney Transplantation Predictor) for classifying phenotypes. By confirming a strong correlation between inflammation and kidney transplantation, our results suggested that the network biomarker but not single factors can potentially classify different phenotypes in kidney transplantation. PMID- 27278390 TI - Seven days in medicine: 1-7 June 2016. PMID- 27278389 TI - Multimodal imaging of the tricuspid valve: normal appearance and pathological entities. AB - The tricuspid valve, which is the atrioventricular valve attached to the morphological right ventricle, is affected by a wide range of pathological processes. Tricuspid valve diseases are now increasingly recognized as a significant cause of morbidity and mortality. Echocardiography is the most widely available and, hence, the first-line imaging modality used in the evaluation of tricuspid valve disorders; however, CT and MRI are also increasingly used for further evaluation and characterization of these entities. In this article, we first review the normal anatomy and embryology of the tricuspid valve, followed by a discussion of the role of multiple imaging modalities in the evaluation of tricuspid valve abnormalities. We then review and illustrate the imaging appearance of several congenital and acquired tricuspid valve abnormalities. Main Messages * Tricuspid valve diseases have a significant impact on morbidity and mortality. * CT and MRI are increasingly used in the evaluation of tricuspid disorders. * CT and MRI help in diagnosis, functional evaluation, pre-surgical planning and post-surgical follow-up. * The most common cause of tricuspid regurgitation is functional. PMID- 27278388 TI - The 100 most cited articles investigating the radiological staging of oesophageal and junctional cancer: a bibliometric analysis. AB - OBJECTIVES: Accurate staging of oesophageal cancer (OC) is vital. Bibliometric analysis highlights key topics and publications that have shaped understanding of a subject. The 100 most cited articles investigating radiological staging of OC are identified. METHODS: The Thomas Reuters Web of Science database with search terms including "CT, PET, EUS, oesophageal and gastro-oesophageal junction cancer" was used to identify all English language, full-script articles. The 100 most cited articles were further analysed by topic, journal, author, year and institution. RESULTS: A total of 5,500 eligible papers were returned. The most cited paper was Flamen et al. (n = 306), investigating the utility of positron emission tomography (PET) for the staging of patients with potentially operable OC. The most common research topic was accuracy of staging investigations (n = 63). The article with the highest citation rate (38.00), defined as the number of citations divided by the number of complete years published, was Tixier et al. investigating PET texture analysis to predict treatment response to neo-adjuvant chemo-radiotherapy, cited 114 times since publication in 2011. CONCLUSION: This bibliometric analysis has identified key publications regarded as important in radiological OC staging. Articles with the highest citation rates all investigated PET imaging, suggesting this modality could be the focus of future research. MAIN MESSAGES: * This study identifies key articles that investigate radiological staging of oesophageal cancer. * The most common topic was accuracy of staging investigations. * The article with the highest citation rate investigated the use of texture analysis in PET images. PMID- 27278391 TI - The impact of developing a pectus center for chest wall deformities. AB - PURPOSE: In 2011, we established a dedicated center for patients with chest wall deformities. Here, we evaluate the center's effect on patient volume and management. METHODS: A retrospective review of 699 patients with chest wall anomalies was performed. Patients were compared, based on the date of initial consultation, before the pectus center opened (July 2009-June 2011, Group 1) versus after (July 2011-June 2013, Group 2). Analysis was performed utilizing Chi square and Mann-Whitney U tests. RESULTS: 320 patients were in Group 1 and 379 in Group 2, an 18.4 % increase in patient volume. Excavatum patients increased from 172 (Group 1) to 189 (Group 2). Carinatum patients increased from 125 (Group 1) to 165 (Group 2). Patients undergoing operative repair of carinatum/mixed defects dropped significantly from 15 % (Group 1) to 1 % (Group 2) (p < 0.01), whereas those undergoing nonoperative bracing for carinatum/mixed defects rose significantly from 19 % (Group 1) to 63 % (Group 2) (p < 0.01). Patients traveled 3-1249 miles for a single visit. CONCLUSION: Initiating a dedicated pectus center increased patient volume and provided an effective transition to nonoperative bracing for carinatum patients. The concentrated focus of medical staff dedicated to chest wall deformities has allowed us to treat patients on a local and regional level. PMID- 27278393 TI - Abstracts for SFCR-August 2016. PMID- 27278395 TI - Combined anterior screw fixation of an odontoid fracture and the atlanto-axial joints (C1/C2) in a geriatric patient. PMID- 27278394 TI - Reduced blood loss and operation time in lumbar posterolateral fusion using a bipolar sealer. AB - PURPOSE: A bipolar sealer using Transcollation(r) technology, a combination of radiofrequency energy and saline, can provide hemostasis at 100 degrees C, which is lower than that used in standard electrocautery. Previous studies of joint arthroplasty have shown that use of the bipolar sealer reduces blood loss and tissue damage during the operation. However, it is unknown whether a bipolar sealer reduces blood loss and tissue damage in lumbar posterolateral fusion (PLF) surgery. The purpose of this study was to analyze the efficacy of this device in limiting blood loss during exposure of the lumbar spine in the treatment of PLF and postoperative pain. METHODS: Fifty patients who underwent PLF were prospectively enrolled between October 2011 and March 2013. Twenty-five patients were randomized to the bipolar sealer group (BS group) and 25 patients to the standard electrocautery group (control group). Operative time and blood loss during exposure of posterior bony elements including the transverse process for PLF, visual analog scale (VAS) to quantify postoperative pain, and the interval from the surgery to hospital discharge were compared. RESULTS: Operative time and blood loss expressed per level of exposure were significantly lower in the BS group than in the control group. There was a tendency toward a lower VAS at postoperative week 1 in the BS group. The duration of hospitalization was 15 and 26 days in the BS and control groups, respectively. CONCLUSIONS: A large randomized control trial adjusted for the number of fusion levels and body mass index is required to confirm the novelty value of this new bipolar sealers. PMID- 27278396 TI - Diversification of the methodology for evaluating cardiac function. PMID- 27278392 TI - Multivariable modeling of factors associated with spinal pain in young adolescence. AB - PURPOSE: To investigate the factors related to the 1-month period prevalence of low back pain (LBP), neck pain (NP) and thoracic spine pain (TSP) in young adolescents, thereby considering potential correlates from the physical, sociodemographic, lifestyle, psychosocial and comorbid pain domains. METHODS: In this cross-sectional baseline study, 69 factors potentially associated with spinal pain were assessed among 842 healthy adolescents before pubertal peak growth. With consideration for possible sex differences in associations, multivariable analysis was used to simultaneously evaluate contributions of all variables collected in the five domains. RESULTS: A significantly higher odds of LBP was shown for having high levels of psychosomatic complaints (odds ratio: 4.4; 95 % confidence interval: 1.6-11.9), a high lumbar lordotic apex, retroversed pelvis, introverted personality, and high levels of negative over positive affect. Associations with a higher prevalence and odds of NP were found for psychosomatic complaints (7.8; 2.5-23.9), TSP in the last month (4.9; 2.2 10.8), backward trunk lean, high levels of negative over positive affect and depressed mood. Having experienced LBP (2.7; 1.3-5.7) or NP (5.5; 2.6-11.8) in the preceding month was associated with a higher odds of TSP, as were low self esteem, excessive physical activity, sedentarism and not achieving the Fit-norm. CONCLUSIONS: Psychosomatic symptoms and pain comorbidities had the strongest association with 1-month period prevalence of spinal pain in young adolescents, followed by factors from the physical and psychosocial domains. The role that "physical factors" play in non-adult spinal pain may have been underestimated by previous studies. PMID- 27278397 TI - Spatially variant regularization for tissue strain measurement and shear modulus reconstruction. AB - PURPOSE: Regarding the regularization of the displacement vector measurement and shear modulus reconstruction, we propose to properly set the regularization parameters, i.e., to use spatially variant regularization parameters at each point in the region of interest, because the measurement accuracies of the displacements and strains vary spatially. METHOD: As the measurement accuracies of the strains can be evaluated using the correlation coefficient when using the cross-spectrum phase gradient method, preliminarily the regularization parameters were set proportional to the reciprocal of a power of the correlation coefficient. RESULTS AND CONCLUSION: Such a regularization scheme realizes the spatially uniform stabilities of the strain measurement and shear modulus reconstruction. The effectiveness of this method was verified by showing the regularized results of the axial strain measurement and of one-dimensional (1-D) shear modulus reconstruction obtained in vivo from a human liver carcinoma (that was treated by interstitial microwave coagulation therapy) as well as by a 1-D shear modulus reconstruction obtained using an agar phantom. PMID- 27278398 TI - High-resolution real-time three-dimensional acoustic imaging system with a reflector. AB - PURPOSE: We propose an acoustic real-time three-dimensional (3-D) diagnostic imaging system based on a hybrid array-reflector configuration that realizes high time and spatial resolutions with a modest computational load. METHODS: All the elements on a small dense array were excited with proper time delays to transmit a broad beam similar to that of a single transmitter element. The echo was gathered by a concave reflector and received by the dense array. The image of the target was reconstructed by numerical back projection from the defocused image distributed on the array. With this scheme, images of the whole measurement area can be reconstructed from a single transmit and receive event. RESULTS: The number of elements can be reduced to about 1/8.2 that of a dense 2-D array of a digital beamforming system having the same spatial resolution. By weighting individual elements, the sidelobe level could be suppressed to less than -21 dB. The maximum theoretical frame rate is 5000 3-D images/s. This method has a higher signal-to-noise ratio than that of defocused multi-element digital beamforming methods, overcoming conventional phased array performance. CONCLUSION: The proposed scheme is suited for purposes that require high time and spatial resolutions, such as cardiology. PMID- 27278399 TI - Characteristic ultrasonographic features of the encapsulated variant of papillary carcinoma of the thyroid. AB - PURPOSE: The purpose of this study was to evaluate the ultrasonographic and clinical features of the encapsulated variant of papillary carcinoma of the thyroid. METHODS: Of a total of 2020 patients whose papillary carcinoma of the thyroid was treated surgically between 1998 and 2002, 56 patients had the encapsulated variant. Ultrasonographic features of the encapsulated variant of papillary thyroid carcinoma were classified into the following two types based on the shape and character of the border: papillary carcinoma (PC) and follicular tumor (FT). Ultrasonographic features of the PC type are a jagged border and an irregular tumor shape. Those of the FT type are a smooth border and a regular shape (spherical to oval). RESULTS: The PC type was seen in 36 patients and the FT type was found in 20 patients. Both types of encapsulated variant of papillary carcinoma showed cervical lymph node metastases. CONCLUSION: Ultrasonographic findings of the FT type have characteristic features that are similar to those of benign follicular tumors of the thyroid. We should remember that some patients do not show typical and classical features of papillary carcinoma on ultrasonography. PMID- 27278400 TI - Clinical usefulness of quantitative evaluation of visceral fat by ultrasonography. AB - PURPOSE: The aim of this work was to evaluate the usefulness of a proposed method for visceral fat volume assessment by ultrasonography (US) in identifying those at risk of metabolic syndrome, and also to establish the most suitable cutoff level of waist circumference for the diagnosis of visceral adiposity. METHODS: One hundred and fifty-two outpatients with metabolic diseases such as hypertension, diabetes, or dyslipidemia were studied. The total visceral fat volume (total-VFA) was measured by computed tomography (CT), the visceral fat area at the level of the umbilicus was measured by CT (CT-VFA), and the visceral fat area was also measured by US (US-VFA), as we recently proposed. RESULTS: Significant correlation coefficients were found between total-VFA and CT-VFA, US VFA, and waist circumference in men but not in women. The correlation co efficient between US-VFA and waist circumference was significantly positive in men and weakly positive in women. According to receiver-operator characteristic curves, the cutoff value of waist circumference yielding the maximal sensitivity plus specificity for predicting more than 100 cm(2) of US-VFA was 85 cm in men and 84 cm in women. The change in US-VFA was significantly larger than that in waist circumference after a 6-month interval. CONCLUSION: The US-measured visceral fat area is more useful than waist circumference in a clinical setting. PMID- 27278401 TI - Segmental duodenitis: ultrasonographic findings. PMID- 27278402 TI - Common atrioventricular valvular regurgitation as a cause of hydrops fetalis in Down syndrome. PMID- 27278403 TI - A case of pelvic kidney: contrast-enhanced ultrasonographic findings. PMID- 27278406 TI - Behind discoveries, beyond discoveries. PMID- 27278405 TI - Polyphenol- and fibre-rich dried fruits with green tea attenuate starch-derived postprandial blood glucose and insulin: a randomised, controlled, single-blind, cross-over intervention. AB - Polyphenol- and fibre-rich foods (PFRF) have the potential to affect postprandial glycaemic responses by reducing glucose absorption, and thus decreasing the glycaemic response of foods when consumed together. A randomised, single-blind, cross-over study was conducted on sixteen healthy volunteers to test whether PFRF could attenuate postprandial blood glucose in healthy volunteers when added to a source of carbohydrate (starch in bread). This is the first study to examine the effects of a meal comprised of components to inhibit each stage of the biochemical pathway, leading up to the appearance of glucose in the blood. The volunteers were fasted and attended four visits: two control visits (bread, water, balancing sugars) and two test visits (single and double dose of PFRF) where they consumed bread, water and PFRF. Blood samples were collected at 0 (fasted), 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption. The PFRF components were tested for alpha-amylase and alpha-glucosidase inhibitory potential in vitro. Plasma glucose was lower after consumption of both doses compared with controls: lower dose, change in mean incremental areas under the glucose curves (IAUC)=-27.4 (sd 7.5) %, P<0.001; higher dose, IAUC=-49.0 (sd 15.3) %, P<0.001; insulin IAUC was also attenuated by-46.9 (sd 13.4) %, P<0.01. Consistent with this, the polyphenol components of the PFRF inhibited alpha amylase (green tea, strawberry, blackberry and blackcurrant) and alpha glucosidase (green tea) activities in vitro. The PFRF have a pronounced and significant lowering effect on postprandial blood glucose and insulin response in humans, due in part to inhibition of alpha-amylase and alpha-glucosidase, as well as glucose transport. PMID- 27278404 TI - Serological evidence of rift valley fever virus among acute febrile patients in Southern Mozambique during and after the 2013 heavy rainfall and flooding: implication for the management of febrile illness. AB - BACKGROUND: Rift Valley fever virus (RVFV) remains heavily neglected in humans in Mozambique, even though recent outbreaks were reported in neighboring countries in humans and several cases of RVFV in cattle were reported in several districts in Mozambique. FINDINGS: We conducted a cross sectional study during and after severe flooding that occurred in 2013 in Mozambique. Paired acute and convalescent serum samples were tested from febrile patients attending a primary health care unit in a suburban area of Maputo city for the presence of IgG and IgM antibodies against Rift Valley fever virus (RVFV) using enzyme-linked immunosorbent assay (ELISA). Seroconversion of IgG anti-RVFV was observed in 5 % (10/200) of convalescent patients and specific IgM anti-RVFV was detected in one acute patient (0.5 %; 1/200). All sera from acute patient tested negative by real time PCR. CONCLUSION: In conclusion, our results suggest that RVF represent an important but neglected cause of febrile illness following periods of flooding in southern Mozambique. PMID- 27278407 TI - Automatic virtual transducer locating system to assist in interpreting ultrasound imaging. AB - Bodymarkers are used to label the location and orientation of the transducer during ultrasound examination. We attempt to evaluate the usefulness of a new system that indicates transducer location over that of the conventional bodymarker. The proposed system uses an electromagnetic tracking device to track the three-dimensional (3-D) position and orientation of a small electromagnetic receiver attached to the ultrasound transducer relative to a transmitter placed under the bed. The new bodymarker is displayed as a 3-D graphic model. The physique of the examinee is calibrated by representing five locations on the body on the original bodymarker. To evaluate the accuracy of the system visually, we compared the transducer position indicated in the new bodymarker and the actual transducer position in four abdominal sections. Actual and displayed position and orientation closely agreed in all cases, and the transducer position indicator in the bodymarker display moved smoothly. Automatic transducer locator on the virtual 3-D bodymarker accurately indicated its position and orientation. This system is useful and convenient in clinical examinations. PMID- 27278409 TI - Sonographic features of mucus-producing carcinoma of the gallbladder. AB - Few cases of mucus-producing carcinoma of the gallbladder have been reported; accordingly, sonographic features of this entity have not been well described. We discuss two cases of gallbladder carcinoma with marked secretion of mucus that we followed using ultrasound. Acute cholecystitis in these cases resulted from obstruction of the cystic duct by the copious secretion of mucus. Ultrasonography revealed debris-like echoes floating in the lumen of the gallbladder with buoyant migration. Mucus appeared as highly echoic smoke-like or cloud-like masses. Color flow imaging showed no vascularity. The mucus echoes disappeared spontaneously between attacks of cholecystitis. A surgical specimen showed a tumor associated with abundant mucous in the gallbladder. We conclude that mucus-producing carcinoma of the gallbladder should be considered when numerous smoke-like echoes appear in the gallbladder. An accurate diagnosis can be obtained by careful observation using ultrasonography. PMID- 27278408 TI - Significance of acoustic field for the myocardial opacification by intravenous contrast echocardiography. AB - PURPOSE: Myocardial opacification is not always homogeneous even in a normal heart. The aim of this study is to clarify why myocardial opacification is faint at the lateral side of the field or at the part far from the focus point. METHODS: In canine study, videointensity of the opacification at septal and lateral walls of the short axis view was examined by using both electric and mechanical transducers. In in vitro study, acoustic pressure at several points away from the beam direction was measured using a hydrophone in a water tank. In particular, the effect of position of focus point was evaluated with an electronic transducer. RESULTS: In canine experiment, myocardial opacification of the lateral wall was faint with the electronic transducer, however the mechanical one obtained homogeneous opacification. In vitro, using the electronic type the acoustic pressure was low as the beam shifted, laterally, whereas it was almost uniform in the mechanical type. With the electronic type, moreover, the beam width at the near field was not sharp when the focus point was far, resulting in execessive acoustic pressure. CONCLUSION: To obtain homogeneous opacifiction, a homogeneous acoustic field is indispensable. PMID- 27278410 TI - Sonographic features of intra-abdominal abscess caused by spilled stones during laparoscopic cholecystectomy. AB - Spillage of stones into the abdominal cavity resulting from perforation of the gallbladder is one of the common complications of laparoscopic cholecystectomy. Although many surgeons know that stones left in the abdominal cavity can cause late visceral abscess requiring surgical treatment, the sonographic features of such abscesses have not yet to be thoroughly investigated. We investigated the sonographic features of intra-abdominal abscesses caused by spilled stones after laparoscopic cholecystectomy using Hitachi Model EUB-525 (3.5 MHz) and Aloka Model SSD-5500 (3.75 MHz) ultrasound systems. Two thousand thirty-six laparoscopic cholecystectomy procedures were carried out at this institution from 1990 through 2001. During this period, we encountered seven cases of intra abdominal abscess. Three of these cases were symptomatic, but abscess, granulation, or both, were found incidentally by ultrasonography in the other four patients during routine annual health examinations. Laparotomy and open drainage of pus and gallstones from the intra-abdominal abscess were necessary in five cases. Ultrasonography revealed a mass in six of the seven patients. The abscesses were located in either the right subphrenic or subhepatic space on the surface of the liver and were sometimes difficult to distinguish from liver tumors. Ultrasound showed the abscesses as oval, low-echoic, solid masses with posterior enhancement. They ranged from 20 to 58 mm in diameter, had clear margins and highly echoic peripheral rims, and showed lateral shadowing. The lesions also contained several highly echoic spots with acoustic shadows that were thought to be the spilled stones. We conclude that visceral abscess should be considered after laparoscopic cholecystectomy, and that careful observation using ultrasonography is required, especially when the gallbladder is perforated and bile and stones have spilled out. PMID- 27278411 TI - Diagnosis of ischemic heart disease with exercise echocardiography: Comparison of images obtained at peak- and post-exercise. AB - Peak-and post-exercise stress echocardiography were compared with respect to ability to detect coronary artery disease in 138 consecutive patients undergoing supine bicycle stress echocardiography. Sixty of these patients had single-vessel disease; 37, double-vessel disease; and 19, triple-vessel disease. Exercise was performed in the 20- to 30-degree left decubitus position on an echo-bed with an ergometer. Exercise started at 50 watts and was increased in 25-watt every 3 minutes and to a maximum of 150 watts. Two-dimensional echocardiographic images were digitized and assigned in a quad-screen format for nonbiased interpretation. Total wall motion score (TWMS) was the sum of the wall motion score, from normokinesis (0) to dyskinesis (4), of 16 segments. Image quality score index (IQSI) was the mean of the image quality scores in all views. All of the patients underwent coronary arteriography. Significant coronary stenosis was defined as?75% stenosis of the large coronary arteries. Two-dimensional echocardiographic studies were adequate for analysis in 133 patients during the peak-exercise stage (peak-exercise) and in 137 patients 30 to 60 seconds after the end of exercise (post-exercise). TWMS at peak-exercise was higher than at post-exercise, while IQSI at peak-exercise was lower than at post-exercise. Sensitivity at peak exercise versus that at post-exercise was 91% versus 79% (p<0.05); specificity, 76% versus 85%; and diagnostic accuracy, 88% versus 80% (p<0.05), respectively. We conclude that despite poor image quality on exercise echocardiography, better diagnostic accuracy was attained by assessing wall motion changes at peak exercise than at post-exercise. PMID- 27278412 TI - The influence of aging on renal blood flow in human beings. AB - OBJECT: We studied the relationship between age and renal blood flow parameters to determine the clinical significance of using Doppler color flow imaging (CFI) in their measurement. SUBJECTS AND METHODS: One hundred forty-four healthy subjects with no renal or circulatory diseases took part in this study. All subjects were placed in the prone position and examined with CFI. The kidney was visualized in a longitudinal view, and blood flow in the interlobar arteries was studied. Peak systolic flow velocity (Vmax), end-diastolic flow velocity (Vmin), and resistive index (RI) were used as blood flow parameters. RESULTS: Age and Vmax were not significantly associated (p=0.03) in the interlobar artery. Vmin decreased significantly (p<0.01) with age, while RI increased significantly (p<0.01) with age. No statistically significant sex-related renal blood flow parameters were found. DISCUSSION: Ishimura et al have reported that RI was significantly correlated with age in diabetic patients. Here the same result was obtained in healthy subjects. The incidence of arteriosclerosis is known to increase with age. In general, RI is influenced by vascular resistance. Increase in RI with age in this study was explained by the effect of arteriosclerosis on age-related vascular resistance. These results suggest that age should be considered in the study of blood flow in the kidney. PMID- 27278413 TI - Highly mobile pedunculated left atrial appendage thrombus falling into the mitral valve orifice. AB - We treated two patients with atrial fibrillation and stringlike left atrial appendage thrombus: a 66 year-old man who had apical hypertrophic cardiomyopathy and a 86 year-old woman with no underlying heart disease. In the patient with hypertrophic cardiomyopathy, transesophageal echocardiography showed a highly mobile stringlike echo protruding from the left atrial appendage and sometimes falling into the mitral orifice. Pathologic examination after excision proved the stringlike echo to be a pedunculated structure composed of red and white thrombi. Excision of thrombus was also planned for the woman, who had a history of recurrent cerebral embolism. Because her cerebral CT showed infarction with bleeding, however, surgery was postponed. The stringlike mobile thrombus was not detected by transesophageal echocardiography 1 month later, when a new embolic episode affected a foot. Clinical outcomes of these two patients differed remarkably. The critical findings by transesophageal echocardiography which facilitated differential diagnosis from cardiac tumors were: spontaneous contrast echo accompanying mural thrombuslike echo, and low flow velocity in the left atrial appendage. However, the differential diagnosis may be quite difficult in cases of tumors associated with atrial fibrillation. PMID- 27278415 TI - Assessment of acute scrotum by Doppler color flow imaging: A report of four cases. AB - We used an Aloka SSD-2000 ultrasound unit with a 5 MHz convex scanner to assess one case of torsion of the spermatic cord, one case of orchitis, and two cases of epididymitis. Color flow imaging showed absence of blood flow signals in the testis in the case of torsion of the spermatic cord, while blood flow signals in the scrotum were significantly increased in the cases of orchitis and epididymitis. Blood flow signals decreased after chemotherapy. Color flow imaging may thus prove useful in the diagnosis and follow-up of patients with acute scrotum. PMID- 27278414 TI - Rapidly enlarging hepatobiliary cystadenoma. AB - An unusual case of a hepatobiliary cystadenoma caused severe abdominal pain and obstructive jaundice by rapid enlargement in a woman aged 73 years. Magnetic resonance imaging revealed a 12 cm cystic lesion in the left medial segment of the liver and dilatation of the intrahepatic bile ducts. The abdominal pain was worse 4 days later, when magnetic resonance imaging demonstrated enlargement of the cystic lesion, to 14 cm in diameter. Laboratory tests on admission revealed serum alkaline phosphatase, 1342 IU/L; gamma glutamic transpeptidase, 672 IU/L; total serum bilirubin, 7.4 mg/dL; direct bilirubin, 5.8 mg/dL; and carbohydrate antigen 19-9, 37U/mL. Serosanguineous fluid was obtained by emergency percutaneous transhepatic drainage of the cyst, which resolved the patient's abdominal pain. Culture and cytologic examination of the fluid were nondiagnostic. The discharged fluid through dramage tube turned brown, and the total serum bilirubin concentration gradually decreased. Cystography and endoscopic retrograde cholangiography demonstrated communication between the cyst and the intrahepatic bile ducts on the left side of the liver. The cyst was removed by left hepatectomy 14 days after it had been drained. Pathologic examination of the resected specimen confirmed the presence of a hepatobiliary cystadenoma. Although hepatobiliary cystadenoma is a rare benign cystic tumor of the liver, it can become malignant and should thus be excised. PMID- 27278417 TI - Teratogenicity of Artemether-Clindamycin Nanostructured Lipid Carriers in Rats. AB - Currently, artemisinin-based combination therapy is considered the best option in the treatment of malaria. However, toxicity of artemisinins limits their use in pregnancy. In the absence of sufficient toxicity data, the World Health Organization recommends that artemisinins are not to be used in the first trimester of pregnancy and can be used only in second and third trimesters, when other treatments are not available. We have recently observed that drugs loaded in nanolipid carriers are selectively taken up in Plasmodium-infected erythrocytes with a concomitant reduction in the dose required to cure animals. Thus, 20% of the therapeutic dose of artemether-clindamycin (ARM-CP) loaded in nanostructured lipid carriers (NLCs; mean particle size 55 +/- 10 nm) resulted in complete parasite clearance and 100% survival of infected mice. Here, we investigate the teratogenicity of this formulation in rodents (dosing on alternate days from 6th day to 18th day of gestation; 12-15 animals/group). The teratogenicity of drug-free NLCs and artesunate-clindamycin (ARS-CP) solution was also evaluated. We found that the therapeutic dose of ARS-CP caused fetal resorptions (87.5% resorptions in 8 litters), suggesting its unsuitability for use in pregnancy. Artesunate-clindamycin NLCs at therapeutic doses also resulted in ~90% fetal resorptions in 10 litters examined. However, postimplantation losses or fetal malformations were not observed at the dose of ARM-CP NLCs that was required for complete parasite clearance in preclinical trials (ie, 20% of the therapeutic dose). Our data suggest that the NLCs loaded with 20% of the therapeutic dose of ARM-CP may have potential in treating malaria during pregnancy. PMID- 27278418 TI - Clusters of suicides and suicide attempts: detection, proximity and correlates. AB - BACKGROUND: A suicide cluster is defined as a higher number of observed cases occurring in space and/or time than would typically be expected. Previous research has largely focused on identifying clusters of suicides, while there has been comparatively limited research on clusters of suicide attempts. We sought to identify clusters of both types of behaviour, and having done that, identify the factors that distinguish suicide attempts inside a cluster from those that were outside a cluster. METHODS: We used data from Western Australia from 2000 to 2011. We defined suicide attempts as admissions to hospital for deliberate self harm and suicides as deaths due to deliberate self-harm. Using an analytic strategy that accounted for the repetition of attempted suicide within a cluster, we performed spatial-temporal analysis using Poisson discrete scan statistics to detect clusters of suicide attempts and clusters of suicides. Logistic regression was then used to compare clustered attempts with non-clustered attempts to identify risk factors for an attempt being in a cluster. RESULTS: We detected 350 (1%) suicide attempts occurring within seven spatial-temporal clusters and 12 (0.6%) suicides occurring within two spatial-temporal clusters. Both of the suicide clusters were located within a larger but later suicide attempt cluster. In multivariate analysis, suicide attempts by individuals who lived in areas of low socioeconomic status had higher odds of being in a cluster than those living in areas of high socioeconomic status [odds ratio (OR) = 29.1, 95% confidence interval (CI) = 6.3-135.5]. A one percentage-point increase in the proportion of people who had changed address in the last year was associated with a 60% increase in the odds of the attempt being within a cluster (OR = 1.60, 95% CI = 1.29-1.98) and a one percentage-point increase in the proportion of Indigenous people in the area was associated with a 7% increase in the suicide being within a cluster (OR = 1.07, 95% CI = 1.00-1.13). Age, sex, marital status, employment status, method of harm, remoteness, percentage of people in rented accommodation and percentage of unmarried people were not associated with the odds of being in a suicide attempt cluster. CONCLUSIONS: Early identification of and responding to suicide clusters may reduce the likelihood of subsequent clusters forming. The mechanisms, however, that underlie clusters forming is poorly understood. PMID- 27278419 TI - Versatile bonding and coordination modes of ditriazolylidene ligands in rhodium(iii) and iridium(iii) complexes. AB - Metalation of novel ditriazolium salts containing a trimethylene (-CH2CH2CH2-) or dimethylether linker (-CH2OCH2-) was probed with different rhodium(iii) and iridium(iii) precursors. When using [MCp*Cl2]2, a transmetalation protocol via a triazolylidene silver intermediate was effective, while base-assisted metalation with MCl3via sequential deprotonation of the triazolium salt with KOtBu and addition of the metal precursor afforded homoleptic complexes. The N-substituent on the triazole heterocycle directed the metalation process and led to Ctrz,Ctrz,CPh-tridentate chelating ditriazolylidene complexes for N-phenyl substituents. With ethyl substituents, only Ctrz,Ctrz-bidentate complexes were formed, while metalation with mesityl substituents was unsuccessful, presumably due to steric constraints. Through modification of the reaction conditions for the metalation step, an intermediate species was isolated that contains a Ctrz,CPh-bidentate chelate en route to the formation of the tridentate ligand system. Accordingly, Cphenyl-H bond activation occurs prior to formation of the second metal-triazolylidene bond. Stability studies with a Ctrz,Ctrz,CPh tridentate chelating ditriazolylidene iridium complex towards DCl showed deuterium incorporation at both N-phenyl groups and indicate that Cphenyl-H bond activation is reversible while the Ctrz-Ir bond is robust. The flexible linker between the two triazolylidene donor sites provides access to both facial and meridional coordination modes. PMID- 27278420 TI - Dreaming of fetal ICU. PMID- 27278421 TI - Differential cytotoxicity and sonosensitization by sanazole: effect of cell type and acoustic parameters. AB - PURPOSE: Although sanazole has been used as a hypoxic radiosensitizer, we recently reported on its ability to sensitize U937 cells to hyperthermia and X irradiation under aerobic conditions, enhancing apoptotic cell death following the combined treatment. The current study was undertaken to evaluate the effect of sanazole as a sonosensitizer under previously studied acoustic conditions of different pulse repetition frequencies, using two cell lines representative of solid tumours and haematopoietic cancers. METHODS: Cells were treated with different doses of sanazole. Flow-cytometric analysis and DNA fragmentation assay were carried out at different times, and morphological features were also inspected. For ultrasound treatment, cells were pre-incubated with a non cytotoxic dose of sanazole for 30 min before exposure. Evaluation of cell killing and a parallel examination of intracellular oxidative stress levels in both cell lines were performed using flow cytometry. RESULTS: Sanazole alone displayed selective cytotoxic effects towards solid tumour-derived cancer cells, resulting in complete cell death after 24 h of treatment, and enhanced the ultrasound induced cell killing 6 h post-treatment. The enhancement seemed to be mediated by an additive increase in intracellular oxidative stress levels. CONCLUSION: Sanazole seems to be an efficient cytotoxic agent for the treatment of solid tumours and a promising sonosensitizer under aerobic conditions. PMID- 27278422 TI - Small calcification depiction in ultrasound B-mode images using decorrelation of echoes caused by forward scattered waves. AB - PURPOSE: The purpose of this study is to propose a novel method to depict small calcifications in ultrasound B-mode images using decorrelation of forward scattered waves with no decrease in the frame rate. METHODS: Since the waveform of an ultrasound pulse changes when it passes through a calcification location, the echo waveform from regions behind the calcification is quite different from that without a calcification. This indicates that the existence of a calcification is predictable based upon the waveform difference between adjacent scan lines by calculating cross-correlation coefficients. In addition, a high intensity echo should return from the calcification itself. Therefore, the proposed method depicts the high-intensity echo positions with posterior low correlation coefficient regions. RESULTS: Eleven of 15 wires 0.2-0.4 mm in diameter were depicted using this method, yielding a sensitivity of 73.3% and a specificity of 100%, even though they might go undetected under clinical inspection of ultrasound B-mode images. CONCLUSION: This study suggests that an US device could perform well in terms of calcification detection. PMID- 27278423 TI - Extraction of instantaneous changes in arterial walls with sequential ultrasound images. AB - PURPOSE: Many structural and dynamic properties of the arterial wall, e.g., lumen diameter and wall thickness, can be measured with non-invasive ultrasound techniques. We present a new computerized analysis method for measurement of instantaneous changes in far and near arterial walls in sequential ultrasound images. METHODS: In this method, two algorithms, i.e., maximum gradient and dynamic programming, were composed and implemented. Reference points and cost function were based on dynamic programming and maximum gradient, respectively. To evaluate this method, B-mode abdominal aorta ultrasound examinations were obtained for ten New Zealand White rabbits. Approximately 70 sequential ultrasound images spanning three cardiac cycles were analyzed from each examination to detect instantaneous changes in the far and near walls and lumen diameter of rabbit abdominal aorta. The maximum, minimum, and mean diameters extracted by the automated method were compared with the same parameters measured by manual tracing. RESULTS: There was no significant differences between the manual and automated methods according to paired t test analysis (p > 0.05). In a verification study, the correlation between the two methods was calculated (R (2) = 0.98, p < 0.05). Agreement between the automated and manual methods as determined by the Bland-Altman approach was excellent. CONCLUSION: It is concluded that the new computerized analysis method is a reliable technique to assess instantaneous changes in the rabbit arterial wall in sequential B-mode images. The variability between different laboratories will be reduced if the same analysis program is used. By using this method, not only was variation in the results of manual tracing by several observers eliminated, but the duration of image processing was also considerably reduced. PMID- 27278424 TI - Distinctive ultrasonographic finding of complete uterine rupture in early mid trimester. AB - In many cases of uterine rupture, diagnosis is often impossible when characteristic clinical symptoms are absent. We encountered a case of suspected peritoneal pregnancy in which we were able to make a definitive diagnosis by ultrasonography of complete uterine rupture in early mid-trimester. The possibly distinctive finding is the high-echo area that extends from the endometrium to the uterine serosa. This contiguous, highly echogenic finding should be recognized as characteristic of complete rupture of the uterus. PMID- 27278425 TI - Degradation of ultrasound probes caused by disinfection with alcohol. AB - The aim of this study was to clarify the degree of degradation of ultrasonic probes that results from their disinfection with alcohol. No defect in the ultrasound beams was found in any of the probes, but a significant decrease of the brightness was found after a certain period of use of the linear-type probe. Disinfection with alcohol may degrade ultrasound probes despite its high degree of effectiveness in preventing iatrogenic bacterial transmission. PMID- 27278426 TI - Misleading image of mechanical valve leaflet by transesophageal echocardiography. AB - Although bileaflet prosthetic valve function is commonly assessed by means of transesophageal echocardiography (TEE) during surgery, the author reports that the leaflet image is not a real image but an artifact. As the depth of the transducer is altered, the leaflet image is gradually skewed in relation to the plane of the prosthetic valve ring. The leaflet-like image consistently overlaps the line that is drawn from the transducer position to the atrial side edge of the leaflet, indicating that this image is caused by reverberations. Three dimensional TEE shows that the leaflet image is not semilunar but is elongated towards the left ventricle and unusually tilted. As viewed from the ventricular side, the ring image is elongated and forms a cylinder-like image in the left ventricle, and the leaflets appear to be opening and closing at the bottom of this cylinder. Therefore, TEE assessment of leaflets in the open position can be misleading. PMID- 27278428 TI - The day when the echocardiographist went mushrooming.... AB - We report a case of partial congenital absence of the pericardium associated with severe aortic stenosis on a bicuspid valve in a 72-year-old man. Diagnosis was based on echocardiography and confirmed with magnetic resonance imaging, and the patient benefited from pericardioplasty and aortic valve replacement. PMID- 27278427 TI - Early diastolic function during exertion influences exercise intolerance in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction (LVEF) often develop dyspnea and exercise intolerance. Diastolic dysfunction may contribute to exercise intolerance in these patients. This study aimed to clarify our hypothesis as to whether diastolic function rather than systolic function would be associated with exercise intolerance in HCM using two-dimensional (2D) speckle tracking echocardiography during exercise. METHODS: Thirty-three HCM patients (mean age 59.3 +/- 15.7 years) underwent 2D speckle tracking echocardiography at rest and during submaximal semi-supine bicycle exercise. Global longitudinal strain (LS), LS rate during systole (LSRs), early diastole (LSRe), and late diastole (LSRa) were measured. The symptom-limited cardiopulmonary exercise testing was performed using a cycle ergometer for measuring the peak oxygen consumption (peak [Formula: see text]). RESULTS: In the multivariate linear regression analysis, peak [Formula: see text] did not associate with strain or strain rate at rest. However, peak [Formula: see text] correlated with LS (beta = -0.403, p = 0.007), LSRe (beta = 6.041, p = 0.001), and LSRa (beta = 5.117, p = 0.021) during exercise after adjustment for age, gender, and heart rate. The first quartile peak [Formula: see text] (14.2 mL/min/kg) was assessed to predict exercise intolerance. The C-statistic of delta LSRe was 0.74, which was relatively greater than that of delta LS (0.70) and delta LSRa (0.58), indicating that early diastolic function rather than systolic and late diastolic function affects exercise intolerance. CONCLUSIONS: LSRe during exercise is closely associated with the peak [Formula: see text]. Early diastolic function during exercise is an important determinant of exercise capacity in patients with HCM. PMID- 27278429 TI - Assessment of mechanical dyssynchrony in fulminant myocarditis. AB - It is often difficult to assess ventricular synchrony in patients with fulminant myocarditis. We report a pediatric case of fulminant myocarditis where clinical course and changes in dyssynchrony were followed with speckle tracking echocardiography. Dyssynchrony of the left ventricle changed day by day. It was useful to assess the progression of ventricular damage and its recovery. PMID- 27278430 TI - Obstruction of mechanical mitral valves by preserved posterior leaflet remnants. AB - We report two cases of mechanical prosthetic mitral valve obstruction caused by remnants of the mitral valve posterior leaflet tissue preserved from the previous surgery. Both patients had rheumatic mitral stenosis causing New York Heart Association class III symptoms prior to mitral valve replacement. PMID- 27278431 TI - An elderly patient with severe aortic stenosis and myocardial infarction with a huge mobile thrombus as complication in the left ventricle. AB - An 86-year-old woman was admitted for emergency treatment of increasing dyspnea. Transthoracic echocardiography revealed decreased left ventricular systolic function with dyskinesis at the apex, and severe aortic stenosis. The apex of the left ventricle showed a huge mobile thrombus. Coronary angiography revealed total occlusion at the middle portion of the left anterior descending coronary artery. Emergency operation was successful, and a partially calcified thrombus was observed at the site of the old myocardial infarction area. In this case, myocardial infarction and elevated intraventricular pressure due to aortic stenosis likely contributed to the wall motion abnormality and thrombus formation. PMID- 27278432 TI - Prothrombin fragment 1+2 as a sensitive marker of intraventricular thrombus formation in a patient with dilated cardiomyopathy: comparison with echocardiography. AB - A 50-year-old man with dilated cardiomyopathy was admitted to our hospital due to heart failure symptoms. Although prothrombin fragment 1+2 (F1+2) was significantly elevated, there was no thrombus in the left ventricle by echocardiography. However, anticoagulation therapy was started because of a possibility of thrombus formation. On the 4th day, F1+2 was persistently elevated and echocardiography detected intraventricular thrombi. After surgical removal of thrombi, F1+2 level decreased rapidly. F1+2 elevation preceded echocardiographic detection of intraventricular thrombi. Therefore, when F1+2 is significantly elevated, echocardiography should be performed meticulously and repeatedly to detect a thrombus. PMID- 27278433 TI - Early diastolic overinflation in diastolic mitral regurgitation. PMID- 27278434 TI - Multiple coronary artery-left ventricle microfistulae. PMID- 27278435 TI - Transient right-sided Serratia endocarditis after a percutaneous transhepatic procedure. PMID- 27278436 TI - Cardiac involvement of malignant lymphoma and its improvement after chemotherapy. PMID- 27278437 TI - Saint Wilgefortis: sudden hirsutism to prevent an unwanted marriage. PMID- 27278438 TI - The "Lost Caravaggio": a probable case of goiter in seventeenth-century Italy. PMID- 27278440 TI - If a joint is hot it's not the time: health professionals' views on developing an intervention to promote physical activity in rheumatoid arthritis. AB - PURPOSE: The study aimed to explore the views of health professionals on (i) physical activity in people who have rheumatoid arthritis (RA) and (ii) the design of an intervention to promote physical activity in this population. METHOD: We used a qualitative methodology and conducted 14 interviews (rheumatologists n = 7, physiotherapist n = 4, clinical nurse specialists n = 3). Interviews were transcribed verbatim and analyzed using thematic analysis. RESULTS: Three key themes were generated: "Personal opinions", "Supporting physical activity" and "An ideal world". Although health professionals viewed physical activity as important, recommending it to people who have RA was largely based on persons' disease status rather than empirical evidence. Resources were highlight as a key challenge to interventions in clinical practice. Supporting physical activity through provision of information, goal setting and monitoring was also discussed. CONCLUSION: Health professionals believe physical activity is important for people who have RA, although there is uncertainty regarding physical activity recommendations for this population. Thus, there is scope to increase health professionals' knowledge of recent evidence. Views varied on how an intervention to promote physical activity should be delivered, but consideration of barriers to delivery in clinical practice is important. Implications for Rehabilitation Physical activity is an important aspect of disease management for people who have rheumatoid arthritis. Health professionals need to acknowledge the "mixed messages" received by people who have RA about being physically active thus further education for health professionals is suggested to standardize physical activity advice in clinical practice. Health professionals may benefit from education about behavior change theory and techniques. When designing future physical activity interventions consideration of the practical challenges of implementing research in a clinical setting is necessary. PMID- 27278439 TI - Drug-induced reactive oxygen species (ROS) rely on cell membrane properties to exert anticancer effects. AB - Pharmacological concentrations of small molecule natural products, such as ascorbic acid, have exhibited distinct cell killing outcomes between cancer and normal cells whereby cancer cells undergo apoptosis or necrosis while normal cells are not adversely affected. Here, we develop a mathematical model for ascorbic acid that can be utilized as a tool to understand the dynamics of reactive oxygen species (ROS) induced cell death. We determine that not only do endogenous antioxidants such as catalase contribute to ROS-induced cell death, but also cell membrane properties play a critical role in the efficacy of ROS as a cytotoxic mechanism against cancer cells vs. normal cells. Using in vitro assays with breast cancer cells, we have confirmed that cell membrane properties are essential for ROS, in the form of hydrogen peroxide (H2O2), to induce cell death. Interestingly, we did not observe any correlation between intracellular H2O2 and cell survival, suggesting that cell death by H2O2 is triggered by interaction with the cell membrane and not necessarily due to intracellular levels of H2O2. These findings provide a putative mechanistic explanation for the efficacy and selectivity of therapies such as ascorbic acid that rely on ROS induced cell death for their anti-tumor properties. PMID- 27278441 TI - Current Approaches to Neuromodulation in Primary Headaches: Focus on Vagal Nerve and Sphenopalatine Ganglion Stimulation. AB - Neuromodulation is a promising, novel approach for the treatment of primary headache disorders. Neuromodulation offers a new dimension in the treatment that is both easily reversible and tends to be very well tolerated. The autonomic nervous system is a logical target given the neurobiology of common primary headache disorders, such as migraine and the trigeminal autonomic cephalalgias (TACs). This article will review new encouraging results of studies from the most recent literature on neuromodulation as acute and preventive treatment in primary headache disorders, and cover some possible underlying mechanisms. We will especially focus on vagus nerve stimulation (VNS) and sphenopalatine ganglion (SPG) since they have targeted autonomic pathways that are cranial and can modulate relevant pathophysiological mechanisms. The initial data suggests these approaches will find an important role in headache disorder management going forward. PMID- 27278442 TI - Value of in situ ovarian volume measured during cesarean delivery to assess the potential of diminished ovarian reserve. AB - OBJECTIVE: We aimed to determine the value of mean ovarian volume (OV) determined by three-dimensional in situ measurement of ovaries during cesarean delivery (CD) to assess the potential of diminished ovarian reserve (DOR) evaluated by hormonal and ultrasonographic parameters 3 months after the cesarean delivery. METHODS: Each ovary was measured underwent CD in three dimensions, and three months after CD, the mean OV, serum AMH, FSH, LH, and estradiol levels, and antral follicle count (AFC) values were recorded as well as other demographic and obstetric parameters. RESULTS: After categorizing the study subjects as having a potential of DOR by the criteria of serum AMH <1 pg/mL and AFC value <=6, in patients with a potential of DOR, the mean intra-operative and post-operative OVs were significantly decreased (p < 0.05). Considering the correlation coefficients obtained by the correlations of post-operative AMH level and AFC value with the mean intra-operative and post-operative OV values, the mean intra-operative OV provided significantly higher correlation coefficients (p < 0.05). CONCLUSIONS: These findings, overall, support the diagnostic value of mean OV determined by the in situ measurement of three dimensions of left and right ovaries during cesarean delivery for the screening of potential for the DOR. PMID- 27278443 TI - Design, synthesis and biological evaluation of novel 1,2,3-triazolyl beta-hydroxy alkyl/carbazole hybrid molecules. AB - The design, synthesis and biological study of several novel 1,2,3-triazolyl [Formula: see text]-hydroxy alkyl/carbazole hybrid molecules as a new type of antifungal agent has been described. In this synthesis, the N-alkylation reaction of carbazol-9-ide potassium salt with 3-bromoprop-1-yne afforded 9-(prop-2-ynyl) 9H-carbazole. The 'Click' Huisgen cycloaddition reaction of 9-(prop-2-ynyl)-9H carbazole with diverse [Formula: see text]-azido alcohols in the presence of copper-doped silica cuprous sulphate led to target molecules in excellent yields. The in vitro antifungal and antibacterial activities of title compounds were screened against various pathogenic fungal strains, Gram-positive and/or Gram negative bacteria. In particular, 1-(4-((9H-carbazol-9-yl) methyl)-1H-1,2,3 triazol-1-yl)-3-butoxypropan-2-ol (10e) proved to have potent antifungal activity against all fungal tests compared with fluconazole and clotrimazole as studied reference drugs. Our molecular docking analysis revealed an appropriate fitting and a potential powerful interaction between compound 10e and an active site of the Mycobacterium P450DM enzyme. The strong hydrogen bondings between [Formula: see text]-hydroxyl and ether groups in 10e were found to be the main factors that drive the molecule to fit in the active site of enzyme. The in silico pharmacokinetic studies were used for a better description of 10a-10n as potential lead antifungal agents for future investigations. PMID- 27278445 TI - Proceedings of the International Summit on Human Gene Editing: a global discussion-Washington, D.C., December 1-3, 2015. AB - The US Academies of Sciences and Medicine, the Royal Society, and the Chinese Academy of Sciences convened a summit of experts in biology, medicine, law, ethics, sociology, and journalism, in December 2015 to review the state of the art in gene editing technology and discuss the medical and social ramifications of the technologies. The summit concluded with the following consensus recommendations: (1) intensive basic and preclinical research in animal and human models should proceed with appropriate legal and ethical oversight; (2) clinical applications in somatic cells must be rigorously evaluated within existing and evolving regulatory frameworks for gene therapy; (3) it would be irresponsible to proceed with any clinical use of germline editing until relevant safety and efficacy issues have been resolved and there is broad societal consensus about such a use; and (4) the international community should strive to establish generally acceptable uses of human germline editing. PMID- 27278444 TI - Synthesis and biological evaluation of novel tamoxifen-1,2,4-triazole conjugates. AB - A new class of compounds, structurally related to the breast cancer drug tamoxifen, was designed and synthesized. The McMurry coupling reaction was used as the key synthetic step in the preparation of these analogs, and the structural assignments were made on the basis of [Formula: see text] NMR, [Formula: see text] NMR, and HRMS studies. The absolute stereochemistry of E and Z isomers was unambiguously confirmed by a single-crystal X-ray diffraction analysis. Water was found to be an inexpensive nontoxic and effective medium for the C-N bond formation. Utilizing this protocol, various tamoxifen derivatives were synthesized in good yields. Environmental acceptability, low cost, and high yields are the important features of this protocol. These compounds were evaluated for their antiproliferative activity on five human tumor cell lines. Compound 4p ([Formula: see text]) showed improved antiproliferative activity against breast cancer cell line (MDA-MB-231) compared to tamoxifen ([Formula: see text]), while the compound 4o ([Formula: see text]) exhibited similar activity against SiHa compared to the reference drug, tamoxifen ([Formula: see text]). In addition, these analogs were investigated for their antibacterial activity against six bacterial strains. Preliminary results indicate that some of the newly synthesized title compounds exhibited promising antibacterial activity compared with the standard drug, vancomycin. A new class of compounds were designed rationally by the replacement of a ethyl group in tamoxifen with a methylene (1H-1,2,4-triazole) group. The absolute stereochemistry of E and Z isomers were unambiguously confirmed by a single-crystal X-ray diffraction analysis. The title compounds were evaluated for their antiproliferative and antibacterial activities. PMID- 27278447 TI - A significant increase in cases of infectious syphilis in men who have sex with men since November 2013. PMID- 27278446 TI - Glu-tubulin is a marker for Schwann cells and can distinguish between schwannomas and neurofibromas. AB - Schwann cells generate myelin sheaths around the axons of the peripheral nervous system, thus facilitating efficient nerve impulse propagation. Two main tumor types can arise from peripheral nerves, schwannomas and neurofibromas, which are sometimes difficult to distinguish and may require the use of diagnostic biomarkers. Here, we characterize a new marker for Schwann cells and its potential use as a diagnostic marker for schwannomas. Immunohistochemistry for Glu-tubulin, a posttranslational modification of alpha-tubulin, was performed in mouse and human tissues. This technique labels Schwann cells but not oligodendrocytes. All peripheral nerves were immunoreactive for this antibody, including large nerve trunks, thin myelinated nerves, as well as the myenteric and submucous plexus of the digestive tract. In the mouse brain, many neurons were immunoreactive for Glu-tubulin but oligodendrocytes were negative. During embryo development, immunoreactive nerves were already found at E10. In Schwann cells, the staining is restricted to the myelin sheaths and is not present in the perinuclear cytoplasm or the Ranvier nodes. Primary cultures of fibroblasts and Schwann cells were established from mouse sciatic nerves, and Western blot analysis showed that Glu-tubulin immunoreactivity was found in the Schwann cells but not in the fibroblasts. Clinical specimens of schwannomas (n = 20) and neurofibromas (n = 20) were stained with anti-Glu-tubulin antibodies. Schwannomas presented a strong staining in all tumor cells, whereas neurofibromas had a light speckled staining pattern, easily distinguishable from the one found in schwannomas. In conclusion, Glu-tubulin can be used as a marker of Schwann cells and can help in diagnosing peripheral nerve tumors. PMID- 27278448 TI - Pubic hair removal and molluscum contagiosum. PMID- 27278449 TI - QFT-IT for diagnosing and screening TB infection in HIV patients: CD4 cells count as an important influential factor. PMID- 27278450 TI - In response to 'Successful treatment of refractory Trichomonas vaginalis infection using intravenous metronidazole' by Hawkins et al. PMID- 27278451 TI - Onychomadesis in a male patient with secondary syphilis. PMID- 27278452 TI - [Incontinence after implantation of an artificial urinary sphincter]. PMID- 27278453 TI - Soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in Indonesia. AB - BACKGROUND: The clinical spectrum of leprosy is dependent on the host immune response against Mycobacterium leprae or the newly discovered Mycobacterium lepromatosis antigen. Helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. The purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and type 2 leprosy reaction (T2R). METHODS: History or episode of T2R was obtained and direct smear, formalin-ether sedimentation technique, and Kato-Katz smear were performed on 20 paucibacillary (PB) and 61 multibacillary (MB) leprosy participants. RESULTS: There are more helminth-positive participants in MB leprosy compared to PB (11/61 versus 0/20, p = 0.034) and in T2R participants compared to non-T2R (8/31 versus 3/50, p = 0.018). CONCLUSIONS: Our results suggest that soil-transmitted helminth infections may have a role in the progression to a more severe type of leprosy, as well as the occurrence of T2R. These findings could serve as a fundamental base for clinicians to perform parasitological feces examination in patients who have MB leprosy and severe recurrent reactions to rule out the possibility of helminth infection. Further secondary confirmation of findings are needed to support these conclusions. PMID- 27278454 TI - Neuroprotective effects of syringic acid against OGD/R-induced injury in cultured hippocampal neuronal cells. AB - Cerebral ischemic injury and treatment are important topics in neurological science. In the present study, an in vitro model of cerebral ischemia was established by subjecting primary cultures of hippocampal neuronal cells to oxygen-glucose deprivation followed by reperfusion (OGD/R), in order to evaluate the possible neuroprotective role of syringic acid (SA). The results of 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays showed that pre-treatment with SA (0.1, 1, 10, and 20 uM) attenuated OGD/R-induced neuronal injury in a dose-dependent manner, with evidence of increased cell viability and decreased LDH leakage. In addition, oxidative stress markers were evaluated using commercial kits, and the results demonstrated that OGD/R exposure induced distinct oxidative stress, accompanied by elevated levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production, and reduced activity of the antioxidant enzyme superoxide dismutase (SOD), which were dose-dependently restored by pre-treatment with SA. In addition, the concentration of intracellular free calcium [Ca2+]i and mitochondrial membrane potential (MMP or Deltapsim) were determined in order to evaluate the degree of neuronal damage by performing flow cytometric analysis and observing the cells under a fluorescence microscope, respectively. We demonstrated that pre-treatment with SA inhibited elevations in [Ca2+]i, whereas it increased the MMP dose-dependently following exposure to OGD/R. Western blot analysis revealed that OGD/R promoted cell apoptosis with concomitant increases in Bax and caspase-3 expression, and reduced Bcl-2 expression, which was reversed by pre-treatment with SA in a dose-dependent manner. Moreover, these effects were mediated through the JNK and p38 pathways, as pre-treatment with SA inhibited the OGD/R-induced increase in phosphorylated (p-)JNK and p-p38 expression. Taken together, these results suggested that SA exerted strong neuroprotective effects in hippocampal neuronal cells, which may be attributed to the attenuation of OGD/R-induced cell injury through the JNK and p38 signaling pathways. PMID- 27278457 TI - Competitive counterion complexation allows the true host : guest binding constants from a single titration by ionic receptors. AB - Counterion competitive complexation is a background process currently ignored by using ionic hosts. Consequently, guest binding constants are strongly affected by the design of the titration experiments in such a way that the results are dependent on the guest concentration and on the presence of added salts, usually buffers. In the present manuscript we show that these experimental difficulties can be overcome by just considering the counterion competitive complexation. Moreover a single titration allows us to obtain not only the true binding constants but also the stoichiometry of the complex showing the formation of 1 : 1 : 1 (host : guest : counterion) complexes. The detection of high stoichiometry complexes is not restricted to a single titration experiment but also to a displacement assay where both competitive and competitive-cooperative complexation models are taken into consideration. PMID- 27278456 TI - Erratum to: Development of a 68Ga-peptide tracer for PET GnRH1-imaging. PMID- 27278455 TI - Functional connectivity change of brain default mode network in breast cancer patients after chemotherapy. AB - INTRODUCTION: Complaint about attention disorders is common among breast cancer patients who have undergone chemotherapy, which may be associated with the default mode network (DMN). To validate this hypothesis, we investigated the DMN functional connectivity (FC) change and its relationship with the attention function in breast cancer patients (BC) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twenty-two BC treated with chemotherapy and 22 healthy controls (HC) were recruited into this study. The FC between the DMN's hubs and regions of the dorsal medial prefrontal cortex (dMPFC) and medial temporal lobe (MTL) subsystems was respectively calculated for each participant. RESULTS: The statistical result showed significantly lower connectivity in dMPFC and MTL subsystems in the BC group. In addition, the partial correlation analysis result indicated that the low connectivity of some brain regions in MTL subsystem was correlated with attention dysfunction following BC chemotherapy. CONCLUSION: These results suggest that the functional disconnection in MTL subsystem of the DMN may have association with attention function of BC after chemotherapy. PMID- 27278458 TI - Serological survey of viral diseases relating to reproductive failure among Artiodactyla in Ethiopian Camelus dromedarius. AB - Serological surveys were performed on Ethiopian camels with a history of abortion to investigate the presence of antibodies against viruses that infect animals classified in the order Artiodactyla. In 2013, 120 serum samples were collected from camels in various parts of Ethiopia. Several viruses related to abortion in ruminants were prevalent. In particular, antibodies against bluetongue virus, were detected at a high rate (76.7% of samples). Additionally, antibodies against Akabane virus and Japanese encephalitis virus were also detected in samples from more than 40% of the camels; however, their antibody titers were relatively low. PMID- 27278459 TI - Peer-engagement and its role in reducing the risky behavior among crack and methamphetamine smokers of the Downtown Eastside community of Vancouver, Canada. AB - BACKGROUND: The role of peers (former or current drug users) in reducing risky behavior within methamphetamine and crack smokers has not been well described or researched. The current study not only explores the role of peers in reducing risk factors for morbidity within the illicit drug smoking population in the Downtown Eastside (DTES) community of Vancouver but it also investigates the changes in the nature of drug use after the closure of an unsanctioned smoking facility. METHODS: The data pertain to qualitative interviews with 10 peers and 10 illicit drug smokers. The semi-structured interviews were conducted through community-based research, and the digital transcripts were analyzed via NVivo 10 software. RESULTS: The results indicate that peers (former and current drug users who are employed as educators) are instrumental in transferring risk reduction knowledge within crack and methamphetamine smokers. For example, these peers have been able to teach users about the risk of sharing pipes, using brillo, and using public drug. Furthermore, the Vancouver Area Network of Drug Users provides employment for crack and methamphetamine users in Vancouver who tend to have scarce sources of employment. However, since the closure of the unsanctioned inhalation facility, there has been significantly more public drug use and pipe sharing in the vicinity of the facility, placing drug smokers at significant risk of arrest, violence, and blood-borne infections. CONCLUSIONS: The current study recommends expanding the harm reduction peer network for people who smoke illicit drugs in the DTES community of Vancouver who have historically been underserved. PMID- 27278460 TI - Prognostic implications of left atrial dilation evaluated by echocardiographic volume in patients with normal left atrial antero-posterior dimensions. AB - BACKGROUND: The purpose of this study was to clarify the clinical characteristics and prognostic implications of left atrial (LA) dilation evaluated echocardiographic volume in patients with normal LA dimension (LAD). METHODS: A total of 140 consecutive patients (81 men, mean age: 57 +/- 18 years) with normal LAD (<39 mm for women and <41 mm for men) who underwent conventional echocardiography and tissue Doppler imaging were enrolled. LA volume (LAV) >=29 ml/m(2) was defined as abnormal LAV. Hospitalization for heart failure (HF) and cardiac death were defined as cardiac events. RESULTS: Eighty-seven (62%) of the patients had LA dilation, defined as a normal LAD but an abnormal LAV. Patients with LA dilation were significantly older and had a significantly higher left ventricular (LV) mass index (LVMI) and incidences of hypertension and HF than did patients with both normal LAD and normal LAV. Logistic regression analysis revealed that increased LVMI was an independent (p < 0.01) determinant of LA dilatation. During a follow-up period of 16 +/- 10 months, ten patients had cardiac events. Patients with cardiac events had a higher incidence of LA dilation than those without cardiac events (100 vs. 59%, p < 0.05). A Kaplan Meier survival curve showed that patients with LA dilation had a significantly lower survival rate than those with both normal LAD and normal LAV (log rank 6.1, p = 0.014). CONCLUSIONS: LV hypertrophy is an independent determinant of LA dilation in patients with normal LAD. Assessment of LA morphology using LAV can contribute to risk stratification in patients with normal LAD. PMID- 27278461 TI - Four characteristics of vascular echo suggesting arterial thromboembolism: differentiation from aggravation of atherosclerotic peripheral artery disease. AB - BACKGROUND: Arterial thromboembolism (ATE) leading to acute arterial occlusion can involve life-threatening complications, including limb loss and death, without prompt thrombectomy. Several ATEs are hard to differentiate from acute aggravation of atherosclerotic peripheral artery disease (PAD). We determined four characteristics of vascular echos suggesting ATE for the differentiation from PAD and validated their use. METHODS AND RESULTS: Twenty patients (11 men and 9 women; mean age, 74 years) with ATE confirmed by therapeutic findings and 19 patients with PAD including occlusive lesions (14 men and 5 women; mean age, 78 years) were enrolled. Four hallmarks of vascular echo suggesting ATE were defined as the manifestation of the intima-media complex next to the adventitia (M1), mild to moderate echolucency of the intravascular structure (M2), mobility of the intravascular structure (M3), and the pulsatile movement of the arterial wall (M4) in occlusive arterial lesions. In the ATE group, 6 patients had three positive items, and 14 patients had four positive items. In the PAD group, ten patients had no positive items, and nine patients had one positive item. Using a cutoff score of more than 3 for ATE, the sensitivity was 100%, the specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 100%. CONCLUSIONS: The presented characteristics of vascular echo suggesting ATE could be useful for making the differential diagnosis against PAD. PMID- 27278462 TI - Prediction of the response to beta-blocker therapy in patients with dilated cardiomyopathy: comparison of 123I-MIBG scintigraphy and low-dose dobutamine stress echocardiography. AB - BACKGROUND: In this study, we aimed to compare low-dose dobutamine stress echocardiography (DSE) and iodine 123-metaiodobenzylguanidine (MIBG) scintigraphy for predicting the response to beta-blocker therapy in patients with dilated cardiomyopathy (DCM). METHODS: MIBG imaging was performed in 10 patients with DCM (mean EF 28 +/- 8%), who were subsequently treated with beta-blocker therapy. The heart-to-mediastinum (H/M) MIBG uptake ratio was evaluated in initial and delayed images, and the percent washout ratio of myocardial MIBG was determined. DSE was also performed in all patients to measure left ventricular ejection fraction (LVEF) at rest and during dobutamine infusion (10 MUg/kg/min). LVEF at rest was also assessed by echocardiography before and after 6 months of beta-blocker therapy. RESULTS: LVEF was significantly improved after beta-blocker therapy (28 +/- 8 to 41 +/- 11%, p < 0.001). The relative change in LVEF after beta-blocker therapy was significantly correlated with the relative change in LVEF during DSE (r = 0.68, p < 0.03). The H/M MIBG uptake ratio in both early and delayed imaging was not significantly correlated with the relative change in LVEF in response to beta-blockade therapy. CONCLUSIONS: The relative change in LVEF during DSE, but not MIBG imaging predicted the relative change in LVEF in response to beta blockade therapy in a limited number of DCM patients. PMID- 27278463 TI - Accessory mitral valve in an elderly man on maintenance hemodialysis. AB - This report describes a case of accessory mitral valve in an elderly patient on maintenance hemodialysis. Transesophageal echocardiography revealed a mobile sac like structure with size of 12 * 10 mm(2), which attached to the left ventricular surface of base of the anterior mitral valve leaflet. Mobile stick-like structure with diameter of 21 mm was extending from this sac-like structure toward the left ventricular outflow tract and had a floating free edge. Peak pressure gradient across the left ventricular outflow tract was 32 mmHg. There were no other congenital cardiac anomalies. No clinical findings suggestive of bacterial or nonbacterial vegetation were seen. Also other possibilities of mobile thrombus or calcification were unlikely. These abnormal structures were diagnosed as accessory mitral valve with rudimentary chordae. PMID- 27278464 TI - Band-like left ventricular echogenic artifact. PMID- 27278465 TI - A case of an isolated cleft in the posterior mitral leaflet. PMID- 27278466 TI - Echo findings in aortic dissection and car company symbols. PMID- 27278467 TI - An empirically derived short form of the Hypoglycaemia Fear Survey II. AB - AIMS: To develop an empirically derived short version of the Hypoglycaemia Fear Survey II that still accurately measures fear of hypoglycaemia. METHODS: Item response theory methods were used to generate an 11-item version of the Hypoglycaemia Fear Survey from a sample of 487 people with Type 1 or Type 2 diabetes mellitus. Subsequently, this scale was tested on a sample of 2718 people with Type 1 or insulin-treated Type 2 diabetes taking part in DIALOG, a large observational prospective study of hypoglycaemia in France. RESULTS: The short form of the Hypoglycaemia Fear Survey II matched the factor structure of the long form for respondents with both Type 1 and Type 2 diabetes, while maintaining adequate internal reliability on the total scale and all three subscales. The two forms were highly correlated on both the total scale and each subscale (Pearson's R > 0.89). CONCLUSIONS: The short form of the Hypoglycaemia Fear Survey II is an important first step in more efficiently measuring fear of hypoglycaemia. Future prospective studies are needed for further validity testing and exploring the survey's applicability to different populations. PMID- 27278468 TI - Enhanced function and quality of life following 5 months of exercise therapy for patients with irreparable rotator cuff tears - an intervention study. AB - BACKGROUND: Rotator cuff rupture is associated with dysfunction, pain and muscular weakness related to the upper extremity. Some evidence exists to support the beneficial effect of exercises but there is lack of evidence of which exercises imply the best effect and how physiotherapy should be administered. Therefore, the purpose of this study was to examine the effect of a neuromuscular exercise program for patients with irreparable rotator cuff rupture. METHODS: Based on sample-size calculations thirty patients with chronic irreparable rotator cuff tears (of at least m. supraspinatus and m. infraspinatus) was consecutively included. Twenty-four patients completed the five months training to restore function with focus on centering the humeral head in the glenoid cavity trough strengthening m. deltoideus anterior and m. teres minor. The primary outcome measure was Oxford Shoulder Score which was completed at baseline, 3 and 5 months follow-up. One-way, repeated-measure ANOVA was used if data was normally distributed. Secondary outcome measures included EQ-5D, range of motion, strength and muscle activity. Paired t-test and Wilcoxon Signed Ranks Test was used to the appropriate outcomes. RESULTS: Improvements was seen for both primary and secondary outcomes from baseline to follow-up. Oxford Shoulder Score improved from 25.6 (SD 8.1) at baseline to 33.8 (SD 8.7) at 3 months (p = 0.004) and 37.2 (SD 8.2) at five months (p < 0.001). Range of motion in abduction significantly increased by 34.4 degrees (95 % CI: 11.6-57.2). Strength measured in flexion 45, flexion 90 and abduction also significantly increased at 5 months by 10.2 (95 % CI: 0.8-19.6), 7.0 (95 % CI: 0.0-14.0) and 12.3 (95 % CI: 3.4-21.3) respectively. The remaining outcomes for range of motion and strengths only showed small and non-significant changes. Furthermore patients reported higher levels of quality of life and reduced level of pain after five months. CONCLUSION: Following a five months exercise protocol patients with irreparable rotator cuff tears showed increased function in their symptomatic shoulder, reduced pain and increased quality of life. This study therefore supports the use of exercise therapy in patients with irreparable rotator cuff rupture. TRIAL REGISTRATION: This study is approved by The National Committee on Health Research Ethics (N-20120040) and registered retrospectively at ClinicalTrials.gov in April 2016 ( NCT02740946 ). PMID- 27278469 TI - 'It is just the way it was in the past before I went to test': a qualitative study to explore responses to HIV prevention counselling in rural Tanzania. AB - BACKGROUND: Voluntary counselling and testing (VCT) for HIV first evolved in Western settings, with one aim being to promote behaviours which lower the risk of onward transmission or acquisition of HIV. However, although quantitative studies have shown that the impact of VCT on sexual behaviour change has been limited in African settings, there is a lack of qualitative research exploring perceptions of HIV prevention counselling messages, particularly among clients testing HIV-negative. We conducted a qualitative study to explore healthcare worker, community and both HIV-negative and HIV-positive clients' perceptions of HIV prevention counselling messages in rural Tanzania. METHODS: This study was carried out within the context of an ongoing community HIV cohort study in Kisesa, northwest Tanzania. Nine group sessions incorporating participatory learning and action (PLA) activities were conducted in order to gain general community perspectives of HIV testing and counselling (HTC) services. Thirty in depth interviews (IDIs) with HIV-negative and HIV-positive service users explored individual perceptions of HIV prevention counselling messages, while five IDIs were carried out with nurses or counsellors offering HTC in order to explore provider perspectives. RESULTS: Two key themes revolving around socio-cultural and contextual factors emerged in understanding responses to HIV prevention counselling messages. The first included constraints to client-counsellor interactions, which were impeded as a result of difficulties discussing private sexual behaviours during counselling sessions, a hierarchical relationship between healthcare providers and clients, insufficient levels of training and support for counsellors, and client concerns about confidentiality. The second theme related to imbalanced gender-power dynamics, which constrained the extent to which women felt able to control their HIV-related risk. CONCLUSION: Within the broader social context of a rural African setting, HIV prevention counselling based on a Western model of individual-level agency seems unlikely to make a significant contribution to sexual behaviour change until there is greater recognition by counsellors of the ways in which power dynamics within many relationships influence behaviour change. More culturally relevant counselling strategies and messages and infrastructural improvements such as additional training for counsellors and counselling rooms which ensure privacy and confidentiality, may lead to better outcomes in terms of sexual risk reduction. PMID- 27278470 TI - The Editors' Medal 2016. PMID- 27278472 TI - Antecedents of Treatment Resistant Depression in Children Victimized by Peers. AB - Children victimized by peers are at increased risk of ongoing depression. This study investigates treatment resistant depression in children victimized by peers, following participation in a targeted cognitive behavioral family intervention. The sample comprised 39 children aged 6-12 years with elevated depression compared with a general sample, prior to the intervention. Six months after the intervention, 26 were no longer depressed and 13 were still depressed. This study investigated the differentiation of these two groups on the basis of parenting and child factors. Children with treatment resistant depression were discriminated from other children by lower levels of peer support and facilitative parenting immediately after the intervention. It was concluded that ongoing support from parents and peers is needed to reduce the risk of ongoing depression even if victimization has been reduced. Further research could develop a comprehensive profile of children at risk of depression following peer victimization. PMID- 27278471 TI - Pigment epithelium-derived factor (PEDF): a novel trophoblast-derived factor limiting feto-placental angiogenesis in late pregnancy. AB - The rapidly expanding feto-placental vasculature needs tight control by paracrine and endocrine mechanisms. Here, we focused on paracrine influence by trophoblast, the placental epithelium. We aimed to identify differences in regulation of feto placental angiogenesis in early versus late pregnancy. To this end, the effect of conditioned media (CM) from early and late pregnancy human trophoblast was tested on network formation, migration and proliferation of human feto-placental endothelial cells. Only CM of late pregnancy trophoblast reduced network formation and migration. Screening of trophoblast transcriptome for anti angiogenic candidates identified pigment epithelium-derived factor (PEDF) with higher expression and protein secretion in late pregnancy trophoblast. Addition of a PEDF-neutralizing antibody restored the anti-angiogenic effect of CM from late pregnancy trophoblast. Notably, human recombinant PEDF reduced network formation only in combination with VEGF. Also in the CAM assay, the combination of PEDF with VEGF reduced branching of vessels below control levels. Analysis of phosphorylation of ERK1/2 and FAK, two key players in VEGF-induced proliferation and migration, revealed that PEDF altered VEGF signaling, while PEDF alone did not affect phosphorylation of ERK1/2 and FAK. These data suggest that the trophoblast-derived anti-angiogenic molecule PEDF is involved in restricting growth and expansion of the feto-placental endothelium predominantly in late pregnancy and targets to modulate the intracellular effect of VEGF. PMID- 27278473 TI - Negative Bystander Behavior in Bullying Dynamics: Assessing the Impact of Social Capital Deprivation and Anti-social Capital. AB - Bystanders witness bullying, but are not directly involved as a bully or victim; however, they often engage in negative bystander behavior. This study examines how social capital deprivation and anti-social capital are associated with the likelihood of engaging in negative bystander behavior in a sample (N = 5752) of racially/ethnically diverse rural youth. Data were collected using an online, youth self-report; the current study uses cross sectional data. Following multiple imputation, a binary logistic regression with robust standard errors was run. Results partially supported the hypothesis and indicated that social capital deprivation in the form of peer pressure and verbal victimization and anti-social capital in the form of delinquent friends, bullying perpetration, verbal perpetration, and physical perpetration were significantly associated with an increased likelihood of engaging in negative bystander behavior. Findings highlight the importance of establishing sources of positive social support for disenfranchised youth. PMID- 27278475 TI - A mechatronics platform to study prosthetic hand control using EMG signals. AB - In this paper, a low-cost mechatronics platform for the design and development of robotic hands as well as a surface electromyogram (EMG) pattern recognition system is proposed. This paper also explores various EMG classification techniques using a low-cost electronics system in prosthetic hand applications. The proposed platform involves the development of a four channel EMG signal acquisition system; pattern recognition of acquired EMG signals; and development of a digital controller for a robotic hand. Four-channel surface EMG signals, acquired from ten healthy subjects for six different movements of the hand, were used to analyse pattern recognition in prosthetic hand control. Various time domain features were extracted and grouped into five ensembles to compare the influence of features in feature-selective classifiers (SLR) with widely considered non-feature-selective classifiers, such as neural networks (NN), linear discriminant analysis (LDA) and support vector machines (SVM) applied with different kernels. The results divulged that the average classification accuracy of the SVM, with a linear kernel function, outperforms other classifiers with feature ensembles, Hudgin's feature set and auto regression (AR) coefficients. However, the slight improvement in classification accuracy of SVM incurs more processing time and memory space in the low-level controller. The Kruskal-Wallis (KW) test also shows that there is no significant difference in the classification performance of SLR with Hudgin's feature set to that of SVM with Hudgin's features along with AR coefficients. In addition, the KW test shows that SLR was found to be better in respect to computation time and memory space, which is vital in a low-level controller. Similar to SVM, with a linear kernel function, other non-feature selective LDA and NN classifiers also show a slight improvement in performance using twice the features but with the drawback of increased memory space requirement and time. This prototype facilitated the study of various issues of pattern recognition and identified an efficient classifier, along with a feature ensemble, in the implementation of EMG controlled prosthetic hands in a laboratory setting at low-cost. This platform may help to motivate and facilitate prosthetic hand research in developing countries. PMID- 27278474 TI - Recruitment of young adults for weight gain prevention: randomized comparison of direct mail strategies. AB - BACKGROUND: Recruiting young adults (ages 18-35 years) into weight gain prevention intervention studies is challenging and men are particularly difficult to reach. This paper describes two studies designed to improve recruitment for a randomized trial of weight gain prevention interventions. Study 1 used a quasi experimental design to test the effect of two types of direct mailings on their overall reach. Study 2 used a randomized design to test the effect of using targeted messages to increase recruitment of men into the trial. METHODS: For Study 1, 60,000 male and female young-adult households were randomly assigned to receive either a recruitment brochure or postcard. Visits to recruitment websites during each mailing period were used to assess response to each mailing. Study 2 focused on postcard recruitment only. These households received either a targeted or generic recruitment postcard, where targeted postcards included the word "Men" in the headline text. Response rates to each type of card were categorized based on participant report of mailing received. RESULTS: The reach of the postcards and brochures were similar (421 and 386 website visits, respectively; P = 0.22). Individuals who received the brochure were more likely to initiate the online screener than those who received a postcard (P = 0.01). In Study 2, of those who completed the telephone screening, 60.9 % of men (n = 23) had received the targeted postcard as compared to the generic postcard (39.1 %, P = 0.30). The reverse was true for women (n = 62, 38.7 vs. 61.3 %, P = 0.08). CONCLUSIONS: These studies suggest there was little difference in the reach of postcards versus brochures. However, recipients of brochures were more likely to continue to the next stage of study participation. As expected, men's response to the weight gain prevention messages was lower than women's response; but using targeted messages appears to have modestly increased the proportion of male respondents. These studies add to the limited experimental literature on recruitment messaging and provide further indication for using targeted messages to reach underrepresented populations while providing initial evidence on the effect of mailing type on message reach. TRIAL REGISTRATION: The Study of Novel Approaches to Weight Gain Prevention was registered with ClinicalTrials.gov (identifier: NCT01183689 ) on 13 August 2010. PMID- 27278476 TI - Influence of neoadjuvant chemoradiotherapy on the anal sphincter: ultrastructural damage may be critical. AB - BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in addition to the curative surgery has been the first of treatment for local advanced rectal cancer because of its benefits in local recurrence and sphincter-saving. However, its side effects on anorectal function have been recognized. The histopathological changes on internal anal sphincter (IAS) have been reported, but ultrastructure changes of external anal sphincter (EAS) are unknown. The aim of this study is to detect the alterations on the gross morphology of IAS and ultrastructure of EAS after nCRT. METHODS: We collected 34 anal canal specimens of patients undergoing abdominoperineal resection (APR) prospectively. The length and thickness of IAS were measured with vernier caliper. The EAS was dissected for observation with transmission electron microscope (TEM). RESULTS: Ten patients received nCRT (nCRT group) before surgery and 24 underwent APR directly (control group). The length and thickness of IAS in nCRT group were 22.68 +/- 3.56 and 5.39 +/- 0.74 mm, respectively. These parameters were 21.28 +/- 3.62 and 5.35 +/- 1.12 mm in control group, respectively. There were no significant differences in the length and thickness of IAS between the two groups (P>0.05). In nCRT group, the sarcomere and myofibril were arranged disorderly and parts of them that were filled with collagenous fiber, triads, and mitochondria were destroyed severely and the glycogenosome also distributed disorderly. Such alterations of EAS did not occur in control group. CONCLUSIONS: The nCRT cannot change the gross morphology of IAS, while it induces serious damages to the ultrastructures of EAS which may adversely affect the anorectal function. PMID- 27278478 TI - The objectivity of ultrasonic diagnosis. PMID- 27278477 TI - Enhanced external counterpulsation (EECP) decreases advanced glycation end products and proinflammatory cytokines in patients with non-insulin-dependent type II diabetes mellitus for up to 6 months following treatment. AB - AIMS: Enhanced external counterpulsation (EECP) is a noninvasive, non pharmacologic intervention proven to increase nitric oxide bioavailability in patients with coronary artery disease. The purpose of the present study was to evaluate the potential clinical benefits of EECP on advanced glycation end products (AGEs) and proinflammatory cytokine concentrations in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). METHODS: Thirty subjects (60.7 +/- 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched standard care (n = 10). AGEs, receptors for AGEs (RAGEs), soluble vascular cell adhesion molecules-1 (sVCAM-1), and 8-iso-prostaglandin 2alpha (8-iso-PGF2alpha) were evaluated before and at 48 h, 2 weeks, 3, and 6 months following EECP treatment or time-matched control. RESULTS: EECP significantly decreased AGEs and RAGEs at all follow-up measurement time points. AGEs and RAGEs were decreased at 48 h (-75 and -16 %), 2 weeks (-87 and -28 %), 3 months (-89 and -29 %), and 6 months (-92 and -20 %) following EECP treatment, respectively. sVCAM-1 and 8-iso-PGF2alpha were significantly decreased at 48 h (-30 and -49 %) and 2 weeks (-22 and -27 %) following EECP, respectively. sVCAM-1 (-27 %) remained significantly reduced at 3 months following EECP. Nitrite/nitrate (NOx) was significantly increased at 48 h (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. CONCLUSIONS: Our findings provide novel evidence that EECP decreases AGE/RAGE concentrations, inflammation, and oxidative stress in patients with T2DM that persist for up to 6 months following treatment. PMID- 27278479 TI - Shear modulus reconstruction by ultrasonically measured strain ratio. AB - PURPOSE: In addition to a description of our three previously developed one dimensional (1D) methods from the viewpoint of shear modulus reconstruction using the strain ratio, two new methods for stabilizing the 1D methods are described, together with their limitations. As confirmed using human in vivo breast tissues, method 1 for evaluating the strain ratio itself is useful when the measurement accuracy of the strain distribution is high. However, because tissues having high shear moduli, such as scirrhous carcinoma, often form singular points/regions, both methods 2 and 3 using the strain ratio (initial estimate) and a regularization method are effective for realizing a unique, stable, useful shear modulus reconstruction. Because method 3 carries out implicit integration only at singular points/regions, whereas method 2 carries out implicit integration throughout the region of interest (ROI), the smaller number of singular points enables more rapid shear modulus reconstruction by method 3 than by method 2. Like method 1, method 3 is also useful when the measurement accuracy of the strain distribution is high. However, when evaluating strain distribution in an ROI with a high spatial resolution to obtain a shear modulus reconstruction having a high spatial resolution, shear modulus reconstructions obtained by methods 1, 2, and 3 often become laterally unstable due to the instability and low accuracy of the strains in the reference regions (reference strains), i.e., regularization in methods 2 and 3 cannot reduce the instability in the initial estimate. METHODS: To cope with this instability, (i) the reconstruction obtained by calculating the strain ratio should be low-pass filtered; for breast tissues, in particular, the reconstruction of the inverse shear modulus should be low-pass filtered, not the reconstruction of the shear modulus. (ii) Otherwise, when using homogeneous regions as a reference, such as a block of reference material, fatty tissue, or parenchyma, evaluation of the reference strains with a low spatial resolution is effective. RESULTS: Although such evaluation yields a stable reconstruction with a high spatial resolution compared with that obtained by the low-pass filtering of the strain ratio, we confirmed through simulations that, when reducing artifacts due to a 1D reconstruction of the shear modulus, the evaluation yields a low-accuracy reconstruction value of inhomogeneity. In contrast, in such a case the low-pass filtering of the strain ratio yields a more accurate reconstruction value. CONCLUSION: All the above-mentioned methods using the strain ratio realize real-time shear modulus reconstruction and should be selected appropriately in conventional ultrasonic imaging equipment by considering the application of the reconstruction (i.e., in accordance with the measurement accuracy of the strains and the occurrence of artifacts). PMID- 27278480 TI - Tissue characterization of uterine myometrium using the ultrasound gray-level histogram width. AB - PURPOSE: The purpose of this study was to clarify the usefulness of the gray level histogram width for tissue characterization of the uterine myometrium. METHODS: Thirty-five patients with uterine fibroids, 5 patients with adenomyosis, and 9 patients with extensive myometrial invasion by endometrial carcinoma were studied. The gray-level histogram width was determined by transvaginal ultrasonography. The Mann-Whitney U test was used for statistical analysis. Receiver operating characteristic curves were generated for use in tissue characterization. RESULTS: Significant differences in the gray-level histogram width were found between normal myometrium (54.2% +/- 4.2%) and carcinoma (58.2% +/- 3.9%), normal myometrium and fibroid (64.3% +/- 5.2%), and carcinoma and fibroid. However, it was difficult to identify adenomyosis. The cutoff values to distinguish normal myometrium from carcinoma, normal myometrium from fibroid, and carcinoma from fibroid are 56, 58, and 64, respectively. CONCLUSION: The gray level histogram width is useful for tissue characterization of the uterine myometrium. PMID- 27278481 TI - A case of adenoid cystic carcinoma of the breast. AB - A 57-year-old woman was referred to our institution 4 months after she noticed a palpable, painless mass in her left breast. Physical examination revealed a mobile and elastic mass. An axillary or subclavicular lymph node was not palpable. Mammography revealed a lobulated mass with a partially ill-defined border. Ultrasonography depicted a 2.5 * 1.5 cm irregularly shaped mass with heterogeneous internal echo and posterior acoustic enhancement. The border of the mass was poorly defined at the anterior and lateral aspects of the mass. Results of ultrasonography-guided fine-needle aspiration cytology were strongly suggestive of a malignant tumor. Thus, the patient underwent breast-conserving surgery with axillary lymph node dissection. The gross resected specimen revealed a gray-to-white and well-demarcated solid tumor measuring 3 * 2 * 2.5 cm, with an irregular border and heterogeneous internal structure. Histological examination showed the characteristic patterns of adenoid cystic carcinoma of the breast. Immunohistochemical studies for both estrogen receptors (ER) and progesterone receptors (PgR) were negative. The patient remains well and has no clinical recurrence of the disease after 5 years of follow-up without radiotherapy or adjuvant therapy. PMID- 27278483 TI - Portal gas in a patient with acute obstructive cholangitis: report of a case with emphasis on US findings. AB - Portal gas is relatively rare, and its relationship to ischemic bowel diseases has been emphasized. We report the case of a 70-year-old woman with acute obstructive cholangitis in whom portal gas was detected by ultrasonography (US) but not by computed tomography (CT). The former showed multiple echo spots moving in the portal vein. Doppler signals confirmed them to be bidirectional and spiky, which immediately led to the diagnosis of portal gas. Immediate appropriate antibiotic treatment and biliary drainage yielded the disappearance of the portal gas. We stress the usefulness of US and Doppler US for detecting and diagnosing portal gas. Our observation suggests that when portal gas is detected by US, the possibility of cholangitis should be included in the differential diagnosis. PMID- 27278482 TI - Quadricuspid aortic valve associated with aortic stenosis and regurgitation: report of a case and a review of the literature. AB - Quadricuspid aortic valve (QAV) is a rare congenital heart valve disease, and more than half of QAV patients have severe aortic regurgitation (AR). We describe the case of a 66-year-old woman with QAV detected by transthoracic echocardiography during a medical checkup. Doppler echocardiographic examination showed mild aortic stenosis and mild AR. The patient has been under routine medical review without medication therapy. At follow-up echocardiographic examinations over a 4-year period, no significant changes in severity of aortic stenosis or AR were found. The clinical and functional characteristics of 192 cases of QAV were reviewed. The functional status of the QAV was known in 144 cases; of these, only 13 (9%) had both aortic stenosis and AR. PMID- 27278484 TI - Usefulness of endoscopic ultrasonography with a microprobe in the diagnosis of aortoesophageal fistula. AB - Aortoesophageal fistula (AEF) is very rare and is associated with a high mortality rate. AEF manifests with massive gastrointestinal bleeding and is difficult to diagnose from endoscopic findings and clinical features. We encountered a patient with an AEF that was promptly diagnosed by endoscopic ultrasonography (EUS) using a microprobe. A 58-year-old man was admitted to our hospital because of hematemesis. Endoscopic examination revealed a submucosal tumor (SMT)-like lesion 2 cm in diameter 25 cm from the dental arch. EUS with a 20-MHz microprobe revealed a blood vessel-like structure with hypoechoic flowing contents and a high echoic area suggestive of a thrombus protruding into the esophageal lumen. AEF resulting from a ruptured thoracic aortic aneurysm was suggested from the EUS findings and was definitely diagnosed by computed tomography. Graft replacement of the descending aorta was successfully performed. The patient is now in good health 6 years after the first admission. This is the first report of a case of AEF diagnosed by EUS with a microprobe. PMID- 27278485 TI - Tissue elastography imaging of the uterine cervix during pregnancy. PMID- 27278488 TI - MESSAGE FROM THE PRESIDENT. PMID- 27278486 TI - Nucleotide composition of the Zika virus RNA genome and its codon usage. AB - BACKGROUND: RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and Central America and the Caribbean in 2015 and has recently been associated with microcephaly in newborns. METHODS: The nearly 11 kb positive-stranded RNA genome of ZIKV was analyzed for its nucleotide composition, also in the context of the folded RNA molecule. Nucleotide trends were investigated along the genome length by skew analyses and we analyzed the codons used for translation of the ZIKV proteins. RESULTS: ZIKV RNA has a biased nucleotide composition in being purine rich and pyrimidine-poor. This preference for purines is a general characteristic of the mosquito-borne and tick-borne flaviviruses. The virus-specific nucleotide bias is further enriched in the unpaired, single-stranded regions of the structured ZIKV RNA genome, thus further imposing this ZIKV-specific signature. The codons used for translation of the ZIKV proteins is also unusual, but we show that it is the underlying bias in nucleotide composition of the viral RNA that largely dictates these codon preferences. CONCLUSIONS: The ZIKV RNA genome has a biased nucleotide composition that dictates the codon usage of this flavivirus. We discuss the evolutionary scenarios and molecular mechanisms that may be responsible for these distinctive ZIKV RNA genome features. PMID- 27278487 TI - Recognition of a novel HLA-DRB1*09 variant, HLA-DRB1*09:25, in a Taiwanese hematopoietic stem cell donor. AB - One nucleotide replacement at codon 91of the HLA-DRB1*09:01:02 results in a novel allele, HLA-DRB1*09:25. PMID- 27278489 TI - EDITORIAL. PMID- 27278490 TI - Estimation of Doppler shift frequency using selected phase information for high frame rate color flow mapping. AB - PURPOSE: We describe a new approach to processing signals used to estimate the Doppler shift frequency in high frame-rate color flow mapping with fewer pulse transmissions. When an ultrasound pulse is transmitted to a large number of scatterers, the echoes from the scatterers overlap and interfere with one another. This interference causes the phase of the received echo signal to fluctuate, thus disturbing the estimated shift in Doppler frequency. The technique proposed here eliminates this disturbed phase information, leaving the remaining information for use in estimating the shift in Doppler frequency. The instantaneous frequency of the echo signal can serve as an index of the influence of interference. METHODS: To test this technique in vivo we used radio-frequency echo signals from the carotid artery for simulation and evaluated the error of the estimated Doppler shift frequency in several cases. CONCLUSION: Performance was enhanced when the number of pulses transmitted was limited and this technique was used. PMID- 27278491 TI - Texture analysis with a new method in which the region of interest is segmented into multiple layers for radiofrequency amplitude histogram analysis of fibrous rat livers. AB - PURPOSE: The aim of this study was to estimate the severity of fibrosis without a biopsy. METHODS: The signal-to-noise ratio (SNR), skewness, and kurtosis were measured using a 10-MHz transducer with the texture analysis in conjunction with an alternative method for evaluating fibrous rat livers. This method segments the region of interest (ROI) into multiple layers (sub-ROIs). In each sub-ROI of a homogeneous medium, the histogram of enveloped amplitude of radiofrequency (RF) backscattered echoes resembles a Rayleigh distribution. In theory, SNR, skewness, and kurtosis for Rayleigh statistics are constant and independent of the mean scattering intensity, which is enhanced by such undesirable effects as tissue attenuation, beam diffraction, and incident waveforms. Thus, these values, which are averages of the corresponding sub-ROI values, constitute an unbiased estimator. All fibrous liver specimens were induced using the dimethylnitrosamine method. Fiber content was estimated quantitatively as the fibrosis index by computer processing of pathological images obtained by light microscopy. RESULTS: The SNR, skewness and kurtosis, expressed as averages of corresponding values from each sub-ROI, correlated closely with the fibrosis index. CONCLUSION: These results make it possible to predict the severity of liver fibrosis from data obtained without resorting to biopsy. The data, obtained from our earlier study on rats, may be used to evaluate human hepatitis quantitatively by measuring these three values. The method may make it possible to estimate the degree of severity of chronic liver disease noninvasively. PMID- 27278492 TI - Diagnosis of acute cholecystitis in patients with liver cirrhosis: waveform analysis of the cystic artery by color Doppler imaging. AB - PURPOSE: The aim of this study was to investigate the possibility of diagnosing acute cholecystitis in patients with liver cirrhosis using color Doppler imaging to demonstrate the hemodynamics. METHODS: Color Doppler imaging was used to analyze the waveform of the cystic artery in 28 cirrhotic subjects with thickened gallbladder walls and 56 normal controls. The cirrhotic group was further divided into the cholecystitis group, containing 6 cirrhotic patients with acute cholecystitis, and the liver cirrhosis group, containing 22 cirrhotic patients without acute cholecystitis. RESULTS: Maximum velocity (Vmax) was significantly higher in the cholecystitis group (31.6 +/- 23.0 cm/s) than in the normal controls (16.1 +/- 5.9 cm/s) (P < 0.01). The resistance index (RI) was higher in the liver cirrhosis group (0.84 +/- 0.04) than in either the normal controls (0.70 +/- 0.06) (P < 0.01) or the cholecystitis group (0.72 +/- 0.09) (P < 0.01). Sensitivity and specificity were 100% when the diagnostic criteria of acute cholecystitis were a maximum velocity of more than 40 cm/s, a resistance index of more than 0.75, or both. CONCLUSION: A pulsatile signal with a maximum velocity of more than 40 cm/s, a resistance index lower than 0.75, or both indicated the presence of acute cholecystitis in patients with liver cirrhosis and a thickened gallbladder wall. PMID- 27278493 TI - Analysis of clinical background in patients with vegetation-like echoes: importance of clinical information. AB - PURPOSE: Detection of vegetation is important for diagnosing infective endocarditis. METHODS: We analyzed clinical information from 58 patients with vegetation-like echoes on transthoracic echocardiography who had been referred to this institution for an echocardiographic examination during the past 5 years. Patients with healed vegetations were excluded. A vegetation-like echo was defined as a mass, a thread-like echo attached to the valve or endocardium, or both. Diagnosis of a vegetation-like echo required the concurrence of two cardiologists and one sonographer. Altogether, 44 patients were treated with antibiotics because their clinical courses were consistent with active infective endocarditis. RESULTS: Blood cultures were positive in 27 patients and negative in 17 patients. Follow-up data were available for 10 of the 14 patients who had no findings suggestive of active infective endocarditis. The size of the vegetation-like echo remained unchanged over a mean interval of 12.1 months, and no clinical signs or symptoms of active infective endocarditis appeared. In about one-fourth of the patients with a vegetation-like echo, it was not associated with infective endocarditis. CONCLUSION: Clinical information, in addition to detection of a vegetation-like echo, appears to be indispensable for diagnosing infective endocarditis. PMID- 27278494 TI - Ultrasonically induced cell damage and membrane lipid peroxidation by photofrin II: mechanism of sonodynamic activation. AB - PURPOSE: Ultrasonically induced cell damage and active oxygen generation with photofrin II were compared using the same in vitro insonation setup. METHODS: Sarcoma 180 cells suspended in an air-saturated phosphate-buffered saline solution were exposed to ultrasound at 2 MHz for not more than 60 s in the presence and absence of photofrin II. The trypan blue exclusion test was used to determine viability. Lipid peroxidation in cell membranes was estimated by measuring the quantity of reactive substance produced from thiobarbituric acid added immediately after the cells had been exposured to ultrasound. RESULTS: Significant enhancement of the rates of ultrasonically induced cell damage and lipid peroxidation was demonstrated with photofrin II (20-80 ug/ml), and the two rates were closely associated. Enhancement of both rates by photofrin II was suppressed by 10 mM of histidine. CONCLUSION: These results suggest that ultrasonically generated active oxygen is a primary factor in ultrasonically induced cell damage in the presence of photofrin II. PMID- 27278495 TI - Case of hemorrhagic pancreatic pseudocyst in which ultrasound imaging was useful. AB - A 50-year-old man was admitted to our institution for upper abdominal pain. The diagnosis was chronic pancreatitis. A pseudocyst 3 cm in diameter had been detected in the head of the pancreas by ultrasonography a year and a half earlier. At the current hospitalization, ultrasound examination showed a mass 5 cm in diameter where the pseudocyst had been seen. This mass comprised an external hypoechoic lesion, a middle movable hyperechoic lesion, and an internal cystic lesion showing an arterial signal on Doppler ultrasound examination. Computed tomography showed a high-density area thought to be a hematoma in the head of the pancreas, and extravasation in the mass was demonstrated by rapid injection of a contrast medium. Our diagnosis was a bleeding pseudocyst. The patient suddenly vomited fresh blood and went into hypovolemic shock on the 11th hospital day. Emergency angiography and transcatheter embolization with steel coils was accomplished under a diagnosis of rupture of the bleeding pseudocyst into the duodenum. Ultrasonographic examination showed that the mass had decreased in size and the cystic lesion, showing an arterial signal, had disappeared after embolization. Although bleeding pseudocysts occur infrequently, they are a life-threatening complication of chronic pancreatitis. Early diagnosis and treatment are thus essential. Ultrasound examination with Doppler ultrasonography is strongly indicated when diagnosing bleeding pseudocysts and examining patients with chronic pancreatitis accompanied by abdominal pain, gastrointestinal bleeding, or both. Early treatment by transcatheter embolization should be used to avoid this potentially lethal complication. PMID- 27278497 TI - What should each of us do now? PMID- 27278496 TI - Psychosocial interventions for infertile couples: a critical review. AB - AIMS AND OBJECTIVES: This critical review aims to identify, summarize and critically appraise the current literature evaluating the effectiveness of psychosocial interventions to improve infertile couples' well-being. It also aims to identify the design implications of effective psychosocial interventions for the management of psychosocial distress in infertile couples, especially culturally specific interventions for Chinese infertile couples. Directions for future research are discussed. BACKGROUND: Infertility is a life crisis affecting 15% of couples in most countries. The affected couples experience considerable psychological distress and impaired interpersonal relationships. Assisted reproductive technologies offer couples hope for pregnancy, but pose an unbearable psychological burden. Psychosocial interventions have been developed to offer support; however, their effectiveness has been inconsistent. DESIGN: A thorough analysis of the literatures on the topic of psychosocial interventions for infertile couples. METHODS: A systematic search of MEDLINE, CINAHL, PsycINFO, British Nursing Index and GoogleScholar from 2003-2015 was conducted to identify English language articles with the keywords 'psychosocial intervention' and 'infertility'. Two authors assessed all of the identified articles independently for inclusion in the review. RESULTS: Twelve studies were included in the review: seven were interventional studies and five were review studies. The findings indicated that the psychosocial interventions in general improved psychological outcomes, marital relationships and pregnancy rates among infertile couples. CONCLUSIONS: Psychosocial interventions should be incorporated into routine practice for infertile couples to provide timely support and counselling. RELEVANCE TO CLINICAL PRACTICE: The implications of the review findings for the effective design of psychosocial interventions, including the content, format, duration and intervener for clinical practice are discussed. In confirming the efficacy of such intervention design, randomized controlled trials are needed to compare the interventions and usual care at clinical setting. Longitudinal design is also needed to examine the long-term effects of psychosocial interventions in infertile couples' well-being. PMID- 27278498 TI - Usefulness of textural analysis as a tool for noninvasive liver fibrosis staging. AB - PURPOSE: Noninvasive diagnosis of liver fibrosis is a popular topic in the medical literature. Textural analysis on B-mode ultrasound is viewed as a noninvasive tool for fibrosis staging. A liver tissue model is proposed and used to simulate ultrasound images. METHODS: One hundred and twenty-five patients with chronic hepatitis C were included in this study. Patients were investigated using B-mode ultrasound and liver biopsy (Metavir scoring). A texture analysis tool consisting of 12 algorithms and a logistic regression classifier was implemented and validated. Tissue model parameters were varied and ultrasound images were generated. RESULTS: Texture analysis can discriminate between stages F0 and F4 using actual patient data (accuracy 69.5%) and synthetic images (accuracy 76.6%). A human expert is less sensitive than texture analysis in discriminating subtle changes in ultrasound images. High fibrosis detection accuracies are correlated with larger differences in portal space density (r (2) = 0.5). Accuracies measured when we varied only the fibrosis stage and kept the rest of the tissue parameters constant showed high detection rates only in a narrow parameter interval. CONCLUSION: The texture analysis system shows limited performance in staging fibrosis and it cannot be used for accurate monitoring of fibrosis evolution over time. PMID- 27278499 TI - Transmission of 100-MHz-range ultrasound through a fused quartz fiber. AB - PURPOSE: This paper describes an investigation into direct observation of microscopic images of tissue using a thin acoustic wave guide. METHODS: First, the characteristics of the ultrasonic wave propagated in a fused quartz fiber were measured using the reflection method in order to study the insertion loss and the frequency shift of the ultrasonic wave transmitted from the transducer. Next, a receiving transducer was placed close to the end of the fiber, and the characteristics of the ultrasonic waves propagated through the acoustic coupling medium were measured using the penetration method in order to study the insertion loss and the frequency-dependent attenuation of the penetrated waves. Finally, a C-mode image was obtained by optimizing the measuring conditions using the results of the above measurements and scanning the ultrasonic beams on a target (coin) in water. RESULTS: A reflected wave with a peak frequency of approximately 220 MHz was obtained from the end of the fiber. The transmitted ultrasonic waves propagated through the acoustic coupling medium were detected with a frequency range of approximately 125-170 MHz, and the maximum detectable distance of the waves was approximately 1.2 mm within the 100-MHz frequency range. Finally, a high-frequency C-mode image of a coin in water was obtained using a tapered fused quartz fiber. CONCLUSION: The results suggest that it is necessary to improve the signal-to-noise ratio and reduce the insertion loss in the experimental system in order to make it possible to obtain microscopic images of tissue. PMID- 27278500 TI - High-frame-rate echocardiography using diverging transmit beams and parallel receive beamforming. AB - PURPOSE: Echocardiography is a widely used modality for diagnosis of the heart. It enables observation of the shape of the heart and estimation of global heart function based on B-mode and M-mode imaging. Subsequently, methods for estimating myocardial strain and strain rate have been developed to evaluate regional heart function. Furthermore, it has recently been shown that measurements of transmural transition of myocardial contraction/relaxation and propagation of vibration caused by closure of a heart valve would be useful for evaluation of myocardial function and viscoelasticity. However, such measurements require a frame rate much higher than that achieved by conventional ultrasonic diagnostic equipment. In the present study, a method based on parallel receive beamforming was developed to achieve high-frame-rate (over 300 Hz) echocardiography. METHODS: To increase the frame rate, the number of transmits was reduced to 15 with angular intervals of 6 degrees , and 16 receiving beams were created for each transmission to obtain the same number and density of scan lines as realized by conventional sector scanning. In addition, several transmits were compounded to obtain each scan line to reduce the differences in transmit-receive sensitivities among scan lines. The number of transmits for compounding was determined by considering the width of the transmit beam. For transmission, plane waves and diverging waves were investigated. Diverging waves showed better performance than plane waves because the widths of plane waves did not increase with the range distance from the ultrasonic probe, whereas lateral intervals of scan lines increased with range distance. RESULTS: The spatial resolution of the proposed method was validated using fine nylon wires. Although the widths at half-maxima of the point spread functions obtained by diverging waves were slightly larger than those obtained by conventional beamforming and parallel beamforming with plane waves, point spread functions very similar to those obtained by conventional beamforming could be realized by parallel beamforming with diverging beams and compounding. However, there was an increase in the lateral sidelobe level in the case of parallel beamforming with plane and diverging waves. Furthermore, the heart of a 23-year-old healthy male was measured. CONCLUSION: Although the contrast of the B-mode image obtained by the proposed method was degraded due to the increased sidelobe level, a frame rate of 316 Hz, much higher than that realized by conventional sector scanning of several tens of Hertz, was realized with a full lateral field of view of 90 degrees . PMID- 27278501 TI - Experimental evaluation of portal venous pulsatile flow synchronized with heartbeat intervals. AB - PURPOSE: The aim of this study was to analyze pulsatile flow in the portal vein, to clarify the origin of pulsatile flow, and to acquire new knowledge about the hepatic circulation. METHODS: Mini-pigs underwent general anesthesia. Pressure and flow in the portal vein, inferior vena cava, hepatic artery, and mesenteric artery were measured simultaneously. We (1) studied the relationship between changes in pressure and changes in flow and (2) measured heartbeat intervals and the onset times of pressure and flow waves. RESULTS: In the inferior vena cava, pressure and flow showed mirror-image changes. In the hepatic artery and the mesenteric artery, pressure and flow increased simultaneously. In the inferior vena cava, the longer the heartbeat interval, the more delayed were the onset times of pressure and flow waves. The onset time of pressure and flow waves in the hepatic artery and the mesenteric artery was only minimally affected by changes in heartbeat interval. The relationship between pressure and flow in the portal vein was closer to that in the hepatic artery and the mesenteric artery. However, the onset times of pressure and flow waves in the portal vein showed two different patterns: some showed a pattern similar to that of the inferior vena cava, whereas others showed a pattern similar to that of the hepatic artery and the mesenteric artery. CONCLUSIONS: Blood flow in the portal vein is pulsatile and influenced by both the inferior vena cava and the arterial system in a complex manner. PMID- 27278502 TI - Determinants of surgical repair of patent ductus arteriosus in low-birth-weight infants. AB - PURPOSE: To identify risk factors related to the failure of indomethacin therapy and the need for surgical repair in patent ductus arteriosus (PDA) in extremely low-birth-weight (<1000 g) infants (ELBWI). METHODS: Study subjects were 36 ELBWI with PDA born at a single tertiary perinatal center. They were classified into those who required surgery due to failure of indomethacin treatment (surgical group, n = 21) and those with effective indomethacin treatment (non-surgical group, n = 15). The odds ratios (ORs) and 95% confidence intervals (95% CIs) for the relationship between selected risk factors and surgical treatment of PDA were calculated. RESULTS: Gestational age of <28 weeks and diameter of PDA of 2 mm or more were independent and significant determinants of the need for surgical repair of PDA (adjusted ORs [95% CIs] = 9.91 [1.16-84.48] and 24.80 [2.72 225.74], respectively). The need for surgical repair of PDA did not correlate with sex, birth weight, 1-min Apgar score, left atrium diameter/aortic diameter (LA/Ao), left ventricular internal dimension at end-diastole, prophylaxes with indomethacin, and total dosage of indomethacin. CONCLUSIONS: Gestational age at birth of <28 weeks and diameter of PDA of 2 mm or more are determinants of failure of indomethacin treatment for PDA and the need for surgical repair. PMID- 27278503 TI - A case of mitochondrial disease with severe left ventricular hypertrophy. AB - A 35-year-old woman was admitted for progressive dyspnea with lower limb edema. Transthoracic echocardiography showed severe left ventricular hypertrophy (LVH) and heart failure with preserved ejection fraction (HFPEF). Electron microscopy of an endomyocardial biopsy sample revealed a high density of mitochondria of abnormal size and shape. We report a case of mitochondrial disease with severe LVH and HFPEF. PMID- 27278504 TI - Secondary aortoduodenal fistula identified by ultrasonography. AB - A 73-year-old man underwent coronary artery bypass grafting, abdominal aortic aneurysm resection, and prosthetic implantation as a single procedure in 2002. His progress was favorable until April 2008, when he was admitted to our hospital with melena. B-mode ultrasonography revealed a 5-mm defect in the abdominal aorta at the graft anastomosis, and an umbilicated lesion was seen projecting between the posterior wall of the third part of the duodenum and the abdominal aorta. A color signal was noticed at this site on color Doppler ultrasonography, leading to the diagnosis of a secondary aortoduodenal fistula (ADF). We resected the inflammatory mass comprising the graft and the third part of the duodenum, and performed prosthetic re-implantation, omentopexy, and duodenojejunostomy. We could not find any previous reports of successful identification of secondary ADF using ultrasonography. When a patient with gastrointestinal hemorrhage following reconstructive aortic surgery is encountered in the emergency department, ultrasonography may be considered to be a useful modality in the diagnosis of secondary ADF. PMID- 27278505 TI - Splenic artery aneurysm that gradually increased in size over 4 years until threatening rupture. AB - A 47-year-old man was referred to our hospital due to a splenic artery aneurysm. The course of the disease was monitored by ultrasound every 6 months. At each examination, the tumor was found to have increased in size by several millimeters, but the sonographer decided that the increase was within the range of error. After 4 years, the tumor showed a rapid increase in size. With a diagnosis of threatened rupture, the patient's life was saved by surgical intervention. In this case, the observations were only compared to the findings from the previous examination, and the slight increase in tumor size was considered within the range of error. It is important to compare the findings not only with those from the previous examination but also with earlier results. PMID- 27278506 TI - Successful prenatal and perinatal management of a massive cervicofacial teratoma. AB - We report a fetus with a massive cervicofacial teratoma successfully managed in the prenatal and perinatal period. A 34-year-old woman was referred to our hospital at 16 weeks' gestation. Ultrasound examination revealed a left anterolateral fetal neck mass indicating typical findings of a teratoma. The tumor grew to tremendous size until occupying most of the uterine cavity causing severe discomfort for the patient. This necessitated ultrasound-guided removal of the intracystic fluid of the massive cervicofacial teratoma during pregnancy. Fetal MRI clearly demonstrated the mass extending from the orbit to the anterior chest wall without compression or deviation of the fetal airway. The entire mass increased to 18 cm in diameter at 37 weeks' gestation. Classical cesarean section was performed immediately after ultrasound-guided removal of the fluid from the cyst. A female infant weighing 3562 g was delivered. Resection of the tumor was accomplished on day 28 of life. The successful outcome in our case illustrates the value of accurate prenatal diagnosis of a giant cervicofacial teratoma using ultrasound and MRI, and careful management of the mother and fetus during the prenatal and perinatal period. It seems that ultrasound-guided removal of the intracystic fluid from the tumor during pregnancy should be considered to prevent preterm delivery. PMID- 27278507 TI - Influence of general anaesthesia on slow waves of intracranial pressure. AB - OBJECTIVE: Slow vasogenic intracranial pressure (ICP) waves are spontaneous ICP oscillations with a low frequency bandwidth of 0.3-4 cycles/min (B-waves). B waves reflect dynamic oscillations in cerebral blood volume associated with autoregulatory cerebral vasodilation and vasoconstriction. This study quantifies the effects of general anaesthesia (GA) on the magnitude of B-waves compared to natural sleep and conscious state. MATERIALS AND METHODS: The magnitude of B waves was assessed in 4 groups of 30 patients each with clinical indications for ICP monitoring. Normal pressure hydrocephalus patients undergoing Cerebrospinal Fluid (CSF) infusion studies in the conscious state (GROUP A) and under GA (GROUP B), and hydrocephalus patients undergoing overnight ICP monitoring during physiological sleep (GROUP C) were compared to deeply sedated traumatic brain injury (TBI) patients with well-controlled ICP during the first night of Intensive Care Unit (ICU) stay (GROUP D). RESULTS: A total of 120 patients were included. During CSF infusion studies, the magnitude of slow waves was higher in conscious patients ( GROUP A: 0.23+/-0.10 mm Hg) when compared to anaesthetised patients ( GROUP B: 0.15+/-0.10 mm Hg; p = 0.011). Overnight magnitude of slow waves was higher in patients during natural sleep (GROUP C: 0.20+/-0.13 mm Hg) when compared to TBI patients under deep sedation (GROUP D: 0.11+/- 0.09 mm Hg; p = 0.002). CONCLUSION: GA and deep sedation are associated with a reduced magnitude of B-waves. ICP monitoring carried out under GA is affected by iatrogenic suppression of slow vasogenic waves of ICP. Accounting for the effects of anaesthesia on vasogenic waves may prevent the misidentification of potential shunt-responders as non-responders. PMID- 27278508 TI - Needs, expectations and consequences for children growing up in a family where the parent has a mental illness. AB - The lack of pan-European guidelines for empowering children of parents with mental illness led to the EU project CAMILLE - Empowerment of Children and Adolescents of Mentally Ill Parents through Training of Professionals working with children and adolescents. The aim of this initial task in the project was to analyse needs, expectations and consequences for children with respect to living with a parent with mental illness from the perspective of professionals and family members. This qualitative research was conducted in England, Finland, Germany, Italy, Norway, Poland and Scotland with 96 professionals, parents with mental illness, adult children and partners of parents with mental illness. A framework analysis method was used. Results of the study highlighted that the main consequences described for children of parental mental illness were role reversal; emotional and behavioural problems; lack of parent's attention and stigma. The main needs of these children were described as emotional support, security and multidisciplinary help. Implications for practice are that professionals working with parents with mental illness should be aware of the specific consequences for the children and encourage parents in their parental role; multi-agency collaboration is necessary; schools should provide counselling and prevent stigma. PMID- 27278510 TI - Coexisting cardiac diseases and pressure recovery phenomenon contribute to discrepancy between the echocardiographic severity of aortic stenosis and left ventricular hypertrophy. AB - BACKGROUND: Assessing left ventricular (LV) hypertrophy (LVH) is an important step in the echocardiographic diagnosis of aortic stenosis (AS). We aimed to investigate the causes of discrepancies between the degrees of AS and LVH. METHODS: The study subjects consisted of 149 consecutive patients with AS having aortic valve area <2.0 cm(2) (mean age 72.5 +/- 11.9 years, 67 men and 82 women). Coexisting cardiac diseases were determined based on echocardiographic findings and comprehensive clinical judgment. Echocardiographic measurements included LV mass index (LVMI), aortic valve area index (AVAI), transaortic mean pressure gradient (MPG), valvulo-arterial impedance (Zva), energy loss coefficient (ELCo), and energy loss index (ELI). RESULTS: LVMI was not significantly correlated with AVAI and Zva, and had a weak correlation with MPG (r = 0.305, p = 0.0001). There were 55 patients in group A (non-severe AS without significant LVH), 58 in group B (non-severe AS with significant LVH), 7 in group C (severe AS without significant LVH), and 29 in group D (severe AS with significant LVH). Coexisting cardiac diseases were more frequently observed (p = 0.0003) in group B (50 %) than in group A (18 %). In group C, ELCo and (ELI - AVAI)/ELI were significantly greater than in group D (p = 0.043 and 0.007, respectively). CONCLUSION: Significant LVH seen in less than moderate AS is often due to coexisting cardiac diseases, and there may be an overestimation of AS severity due to pressure recovery among patients with apparently severe AS who do not have significant LVH. PMID- 27278509 TI - Concurrent Treatment of Substance Use and PTSD. AB - Substance use disorders (SUD) and posttraumatic stress disorder (PTSD) are chronic, debilitating conditions that frequently co-occur. Individuals with co occurring SUD and PTSD suffer a more complicated course of treatment and less favorable treatment outcomes compared to individuals with either disorder alone. The development of effective psychosocial and pharmacological interventions for co-occurring SUD and PTSD is an active and critically important area of investigation. Several integrated psychosocial treatments for co-occurring SUD and PTSD have demonstrated promising outcomes. While recent studies examining medications to treat co-occurring SUD and PTSD have yielded encouraging findings, there remain substantial gaps in the evidence base regarding the treatment of co occurring SUD and PTSD. This review will summarize the findings from clinical trials targeting a reduction in SUD and PTSD symptoms simultaneously. These results may improve our knowledge base and subsequently enhance our ability to develop effective interventions for this complex comorbid condition. PMID- 27278511 TI - Post-exercise diastolic stunning detected by velocity vector imaging is a useful marker for induced ischemia in ischemic heart disease. AB - BACKGROUND: Recently, post-exercise diastolic stunning (PES) has been reported as a new clinical marker of induced ischemia. Velocity vector imaging (VVI) has been developed to visualize regional wall motion abnormalities based on vectors detected by the tissue tracking technique, which has the potential to visualize PES. Thus, the aim of this study was to evaluate the usefulness of PES detection by VVI as an objective marker of ischemia compared to stress thallium-201 (Tl 201) single photon emission computed tomography (SPECT). METHODS: We studied consecutive patients who were scheduled to undergo exercise stress Tl-201 SPECT for the diagnosis of ischemic heart disease. Transthoracic echocardiography was recorded digitally before and 20 min after exercise for Tl-201 SPECT, and the data were used subsequently for VVI analysis. We defined PES regions as those with new abnormal vectors observed during isovolumic relaxation. RESULTS: After excluding 14 patients with old myocardial infarction and/or atrial fibrillation, echocardiograms suitable for VVI analysis were obtained from 62 of 65 patients (feasibility, 95 %; 44 men; mean age, 64 +/- 11 years). SPECT revealed induced ischemia in 20 patients, whereas VVI identified PES in 18 patients. VVI detected inducible ischemia with 85 % sensitivity and 98 % specificity compared to SPECT. CONCLUSIONS: VVI detection of PES is a new clinical tool for induced ischemia. Regional diastolic wall motion abnormalities following induced ischemia can be noninvasively detected by VVI. PMID- 27278512 TI - Possible further reduction in coronary flow velocity reserve in angina pectoris patients after oral glucose loading. AB - BACKGROUND: Previous studies have suggested an increase in myocardial oxygen demand as a cause of postprandial angina. The purpose of this study was to assess coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) before and after glucose ingestion in patients with known significant LAD stenosis. METHODS: Fourteen patients with significant LAD stenosis and 20 subjects without LAD stenosis were enrolled. Transthoracic Doppler echocardiography was performed to measure the average peak diastolic coronary flow velocity (APDV) in the LAD at rest and during adenosine infusion. CFVR was calculated as APDV during adenosine infusion (APDVATP) divided by APDV at rest (APDVrest). APDVrest, APDVATP, and CFVR were assessed during fasting and 30, 60, and 120 min after a 75-g oral glucose loading. RESULTS: In patients with LAD stenosis, APDVrest at 30 min after glucose loading was the highest at any time point. However, significant differences were not found in the APDVATP among time points in the patients or controls. Consequently, the CFVR in the patients was the lowest at 30 min after glucose loading (fasting, 1.77 +/- 0.19; 30 min, 1.48 +/- 0.16; 60 min, 1.69 +/- 0.17; and 120 min, 1.76 +/- 0.19; p < 0.01, ANOVA), as in the controls. CONCLUSIONS: These findings suggested that the value of CFVR in the LAD was reduced after glucose loading. Myocardial risk area supplied by a stenosed coronary artery may be exposed to myocardial ischemia more frequently during oral glucose loading than during fasting in patients with significant coronary artery stenosis. PMID- 27278513 TI - Aortic arch thrombosis in the neonate. AB - Aortic arch thrombosis (AAT) of the neonate is rare but life-threatening by fatal compromise associated with thrombotic obstruction of the ascending aorta. We report a neonate with AAT who demonstrated a severe coarctation of the aorta and cerebral hypo-perfusion immediately after birth. Echocardiography confirmed the diagnosis of AAT on the findings of a large thrombus located on the transverse arch and blocking the cervical arterial branches. Low-molecular-weight heparin reduced the size of the thrombus and improved the hemodynamics of coarctation and cerebral perfusion. Echocardiography is a powerful tool to make a diagnosis and to monitor the size and regression of AAT. PMID- 27278515 TI - Acute aortic regurgitation due to aortic dissection confined to the sinus of Valsalva. AB - A 34-year-old man with severe heart failure was diagnosed with acute aortic regurgitation (AR) by transthoracic echocardiography (TTE). However, this differential diagnosis was incomplete. Only transesophageal echocardiography (TEE) revealed an intimal flap, leading to a diagnosis of Stanford type A aortic dissection. No abnormal findings were observed in the ascending aorta by contrast enhanced computed tomography (CT). Aortic dissection confined to the sinus of Valsalva has rarely been reported; however, TEE should still be considered for the differential diagnosis of acute AR, even if there is no evidence of dissection by TTE or contrast-enhanced CT. PMID- 27278514 TI - Early abnormality detected by speckle-tracking echocardiography in a patient with suspected cardiac sarcoidosis. AB - A 56-year-old female was admitted to our hospital because of respiratory symptoms. Her admission ECG showed normal sinus rhythm and standard echocardiographic evaluation showed no structural or functional abnormalities. She was diagnosed as having sarcoidosis by imaging modalities and mediastinum lymph node biopsy. In this case, 2-dimensional speckle-tracking echocardiography (STE) demonstrated abnormal regional myocardial function and delayed enhancement cardiac magnetic resonance imaging revealed a high intensity area in the same segments. This case suggests that STE is potentially useful for the detection of cardiac sarcoidosis in the early phase. PMID- 27278516 TI - Cor triatriatum dexter with atrial septal defect evaluated by real-time three dimensional transesophageal echocardiography. PMID- 27278517 TI - Clinical utility of automated ablation lesion tagging based on catheter stability information (VisiTag Module of the CARTO 3 System) with contact force-time integral during pulmonary vein isolation for atrial fibrillation. AB - BACKGROUND: The clinical utility of an automated lesion tagging module based on catheter stability information (VisiTag) with the CARTO system during atrial fibrillation (AF) ablation remains to be established. We investigated whether VisiTag-guided extensive encircling pulmonary vein isolation (EEPVI) produces durable lesions. METHODS: The study involved 54 patients undergoing EEPVI for paroxysmal AF. We performed EEPVI guided by the module-generated ablation tags, i.e., "VisiTags," which are point-by-point ablation tags placed on 3D maps. The patients were divided into two groups: those treated under a moderate catheter stability VisiTag setting, i.e., a 3-mm distance limit for at least 5 s and a minimum contact force (CF) of 8 g over 25 % of the set time period with a target force-time integral (FTI) >=300 g*s (n = 27), and those treated under a strict catheter stability setting, i.e., a 3-mm distance limit for at least 10 s and a minimum CF of 10 g over 50 % of the set time period with a target FTI >=400 g*s (n = 27). RESULTS: After EEPVI, adenosine triphosphate-provoked dormant PV conduction was observed in six (22 %) patients in the moderate catheter stability group and in one (4 %) patient in the strict catheter stability group (p = 0.1003); the 12.9-month success rate was 81 % in both groups. CONCLUSIONS: The strict catheter stability setting for automated lesion tagging together with a target FTI of >400 g*s, vs. the moderate catheter stability setting with a target FTI of >300 g*s, produces less frequent ATP-provoked PV conduction and yields a comparably high mid-term success rate. PMID- 27278518 TI - Sequential vision loss in a patient with headache. PMID- 27278519 TI - Inhibition of pentraxin 3 in glioma cells impairs proliferation and invasion in vitro and in vivo. AB - Pentraxin 3 (PTX3) is an inflammatory molecule that is involved in immune responses, inflammation, and cancer. Recent evidence suggests that PTX3 plays a critical role in tumor progression; however, its impact on the biological function of gliomas remains unknown. In the present study, immunohistochemical staining showed that patients with high-grade gliomas exhibited increased expression levels of PTX3 compared to those with low-grade gliomas (P < 0.001). Furthermore, knockdown of PTX3 in GBM8401 cells inhibits proliferation, increases p21 protein levels, and decreases cyclin D1 protein levels, resulting in cell cycle arrest at the G0/G1 phase. In addition, knockdown of PTX3 significantly decreases GBM8401 cell migration and invasion through the downregulation of matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) expression. In a GBM8401 xenograft animal model, PTX3 knockdown decreases tumor growth in vivo. In conclusion, PTX3 plays an important role in glioma cell proliferation and invasion, and may thus serve as a novel potential therapeutic target in the treatment of gliomas. PMID- 27278520 TI - CD4(+)CD25(+) T Cells in primary malignant hypertension related kidney injury. AB - CD4(+)CD25(+) T cells are critical for maintenance of immunologic self-tolerance. We measured the number of CD4(+)CD25(+) cells in the patients with primary malignant hypertension related kidney injury, to explore the molecular pathogenesis of this disease. We selected 30 patients with primary malignant hypertension related kidney injury and 30 healthy volunteers. Information on clinical characteristics and laboratory tests was obtained from each subject. The number of CD4(+)CD25(+) cells and glomerular injury were assessed by flow cytometry and histopathology, respectively. Both serum IL-2, IL-4, and IL-6 and endothelial cell markers were analyzed by ELISA. ADAMTS13 antibody was detected by Western blotting. CD4(+)CD25(+) cells were significantly reduced in patients with primary malignant hypertension related kidney injury compared to controls (P < 0.05). The number of CD4(+)CD25(+) cells was negatively related to blood urea nitrogen, serum uric acid, proteinuria, and supernatant IL-4; whereas positively associated with estimated glomerular filtration rate in patients. Gradually decreasing CD4(+)CD25(+) cells were also found as increasing renal injury. Additionally, patients exhibited increasing supernatant IL-4, serum IL-2 and IL 6, endothelial cell markers, and anti-ADAMTS13 antibody compared with controls (all P < 0.05). CD4(+)CD25(+) cells may play a key role in the pathogenesis of primary malignant hypertension related kidney injury. PMID- 27278521 TI - Heart rate variability (HRV) in deep breathing tests and 5-min short-term recordings: agreement of ear photoplethysmography with ECG measurements, in 343 subjects. AB - PURPOSE: We analyzed heart rate variability (HRV) taken by ECG and photoplethysmography (PPG) to assess their agreement. We also analyzed the sensitivity and specificity of PPG to identify subjects with low HRV as an example of its potential use for clinical applications. METHODS: The HRV parameters: mean heart rate (HR), amplitude, and ratio of heart rate oscillation (E-I difference, E/I ratio), RMSSD, SDNN, and Power LF, were measured during 1 min deep breathing tests (DBT) in 343 individuals, followed by a 5-min short-term HRV (s-HRV), where the HRV parameters: HR, SD1, SD2, SDNN, Stress Index, Power HF, Power LF, Power VLF, and Total Power, were determined as well. Parameters were compared through correlation analysis and agreement analysis by Bland-Altman plots. RESULTS: PPG derived parameters HR and SD2 in s-HRV showed better agreement than SD1, Power HF, and stress index, whereas in DBT HR, E/I ratio and SDNN were superior to Power LF and RMSSD. DBT yielded stronger agreement than s HRV. A slight overestimation of PPG HRV over HCG HRV was found. HR, Total Power, and SD2 in the s-HRV, HR, Power LF, and SDNN in the DBT showed high sensitivity and specificity to detect individuals with poor HRV. Cutoff percentiles are given for the future development of PPG-based devices. CONCLUSION: HRV measured by PPG shows good agreement with ECG HRV when appropriate parameters are used, and PPG based devices can be employed as an easy screening tool to detect individuals with poor HRV, especially in the 1-min DBT test. PMID- 27278522 TI - Aortic augmentation index in endurance athletes: a role for cardiorespiratory fitness. AB - PURPOSE: Endurance exercise improves cardiovascular health and reduces mortality risk. Augmentation index (AIx) reflects adverse loading exerted on the heart and large arteries and predicts future cardiovascular disease. The purpose of this study was to establish whether endurance athletes possess lower AIx and aortic blood pressure compared to healthy controls, and to determine the association between AIx and cardiorespiratory fitness. METHODS: Forty-six endurance athletes and 43 healthy controls underwent central BP and AIx measurements by non-invasive applanation tonometry before a maximal exercise test. Peak oxygen uptake ([Formula: see text]) was assessed by pulmonary analysis. RESULTS: Relative to controls, athletes had significantly lower brachial diastolic blood pressure (BP, -4.8 mmHg, p < 0.01), central systolic BP (-3.5 mmHg, p = 0.07), and AIx at a heart rate of 75 beats min(-1) (AIx@75, -11.9 %, p < 0.001). No AIx@75 differences were observed between athletes and controls when adjusted for age and [Formula: see text] [athletes vs controls mean (%) +/- SE: -6.9 +/- 2.2 vs -5.7 +/- 2.3, p = 0.76]. Relative to men with low [Formula: see text], those with moderate and high [Formula: see text] had lower age-adjusted AIx@75 (p < 0.001). In women, those with high [Formula: see text] had lower AIx@75 than those with low and moderate [Formula: see text] (p < 0.01). CONCLUSIONS: The lower AIx@75 in endurance athletes is partly mediated by [Formula: see text]. While an inverse relationship between AIx@75 and [Formula: see text] was found in men, women with the highest [Formula: see text] possessed lowest AIx@75 compared to females with moderate or poor cardiorespiratory fitness. We recommend aerobic training aimed at achieving a minimum [Formula: see text] of 45 ml kg(-1) min(-1) to decrease the risk of future cardiovascular events and all-cause mortality. PMID- 27278523 TI - The value of combined elevation of D-dimer and neopterin as a predictive parameter for early stage acute mesenteric ischemia: An experimental study. AB - Background The diagnosis of acute mesenteric ischemia is variable. Early diagnosis is important for reducing the mortality and morbidity rates. Aim This experimental study aims to investigate the diagnostic utility of D-dimer and neopterin as a marker for the early stage of acute mesenteric ischemia caused by occlusion of superior mesenteric artery. Methods The levels of D-dimer and neopterin were measured using an animal acute mesenteric ischemia model in 21 male rabbits. Superior mesenteric artery occlusion (Group 1, n = 14) and control (Group 2, n = 7) groups were identified. Blood samples at different times are collected from each rabbits. Blood samples from superior mesenteric artery occlusion group were taken 30 min after anesthesia but before laparotomy, 1, 2, and 3 h after superior mesenteric artery ligation. Blood samples from control group were taken 1 h before, 1 and 3 h after anesthesia and laparotomy. The D dimer and neopterin levels of each blood sample were measured. Results The probability of acute mesenteric ischemia was found to be 36 times higher when the D-dimer level was over 0.125 ng/L, whereas the probability was 19.2 times higher when the neopterin level was over 1.25 nmol/L. Conclusions In this experimental study, the combined elevation of two significant markers, D-dimer and neopterin, may be helpful for the early diagnosis of acute mesenteric ischemia. PMID- 27278524 TI - Rare occurrence of metastasis from lung cancer to the anus: case report and review of the literature. AB - BACKGROUND: Anal metastases from lung cancer are infrequent, and there are only 10 published cases. Life expectancy is no longer than 1 year after diagnosis because of the typically advanced stage of disease. Treatment, which is typically inefficient, is administered with the intent to cure or avoid local complications. CASE PRESENTATION: We report a case of a patient with non-small cell lung cancer presenting with perianal metastasis mimicking an abscess. CONCLUSIONS: Because perianal masses may be misdiagnosed, patients with lung and other cancers should be evaluated for metastatic disease. PMID- 27278525 TI - Fluoxetine synergizes with temozolomide to induce the CHOP-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells. AB - Although temozolomide (TMZ) is the most effective chemotherapy agent for glioma, chemotherapy resistance has limited its clinical use. Fluoxetine (FLT), which is widely used in cancer-related depression, has exhibited potent anticancer properties in different cancer cell types. The aim of this study was i) to evaluate the antitumor mechanism of FLT, and ii) to further evaluate the effects of a combination of FLT and TMZ on glioma cells. Glioma cell lines were exposed to FLT and/or TMZ. Cell viability and apoptosis were examined by CCK-8 assay, flow cytometry and caspase-3 activity assay, respectively. The expression of endoplasmic reticulum-stress (ERS) apoptosis-related proteins was measured using real-time PCR and western blotting. Synergism between the two drugs was evaluated by the combination index (CI) through CompuSyn software. FLT significantly and dose-dependently inhibited the proliferation of various glioma cell lines, and rat glioma C6 cells had a highly sensitive response to the addition of FLT. FLT treatment increased the early apoptosis rate, induced typical apoptotic morphology in the C6 cells and activated caspase-3 with no change in the mitochondrial membrane potential. Further study showed that FLT activated the ERS marker, CHOP. This induction was associated with activation of the PERK-eIF2alpha ATF4 and ATF6 cascade. Concomitantly, GADD34, a downstream molecule of CHOP, was also increased. Combined FLT and TMZ treatment showed a synergistic cytotoxic effect in the C6 glioma cells. Knockdown of CHOP expression abolished the synergistic effect of FLT and TMZ in the C6 cells, which suggests that FLT may sensitize glioma cells to TMZ through activation of the CHOP-dependent apoptosis pathway. These results revealed that FLT induced glioma cell apoptosis and sensitized glioma cells to TMZ through activation of the CHOP-dependent apoptosis pathway. The present study provides a primary basis for using the combination of these drugs in patients with advanced glioma. PMID- 27278527 TI - Large Size Color-tunable Electroluminescence from Cationic Iridium Complexes based Light-emitting Electrochemical Cells. AB - Solution-processable light-emitting electrochemical cells (LECs) with simple device architecture have become an attractive candidate for application in next generation lighting and flat-panel displays. Herein, single layer LECs employing two cationic Ir(III) complexes showing highly efficient blue-green and yellow electroluminescence with peak current efficiency of 31.6 cd A(-1) and 40.6 cd A( 1), respectively, have been reported. By using both complexes in the device, color-tunable LECs with a single spectral peak in the wavelength range from 499 to 570 nm were obtained by varying their rations. In addition, the fabrication of efficient LECs was demonstrated based on low cost doctor-blade coating technique, which was compatible with the roll to roll fabrication process for the large size production. In this work, for the first time, 4 inch LEC devices by doctor-blade coating were fabricated, which exhibit the efficiencies of 23.4 cd A(-1) and 25.4 cd A(-1) for the blue-green and yellow emission, respectively. The exciting results indicated that highly efficient LECs with controllable color could be realized and find practical application in large size lighting and displays. PMID- 27278526 TI - High-resolution melting analysis for molecular detection of multidrug resistance tuberculosis in Peruvian isolates. AB - BACKGROUND: The emergence of multidrug-resistant strains is a major health problem especially for countries with high TB incidence such as Peru. In this study, we evaluated High Resolution Melting (HRM) assay in Peruvian isolates for the detection of mutations within rpoB, katG genes and promoter region inhA to determine isoniazid and rifampicin resistance in Mycobacterium tuberculosis (Mtb). METHODS: DNA samples extracted from a total of 167 clinical isolates of Mtb, 89 drug-sensitive and 78 multidrug-resistant, were blindly analyzed by HRM analysis and verified by DNA sequencing. RESULTS: The HRM analysis generated patterns that were specific to distinguish between sensitive and resistance isolates. The sensitivity and specificity of the HRM assays in comparison with drug susceptibility testing (DST) for detection of rifampicin resistance were 98.7 % and 97.5 %, and for isoniazid resistance were 98.7 % and 100 %. CONCLUSION: This study suggests that HRM Analysis could help with rapid diagnosis of MDR-TB cases in Peru. PMID- 27278528 TI - Management of adrenal incidentaloma: the role of adrenalectomy may be underestimated. AB - BACKGROUND: To demonstrate clinical characteristics of adrenal incidentaloma in South China and explore its comprehensive management. METHODS: The clinical data of patients with adrenal neoplasm from Jan 1998 to Dec 2012 were retrospectively analysed. Patients with suspicion of adrenal abnormalities or those in whom adrenal abnormalities were detected in the staging procedures of other cancers were excluded. Most patients with adrenal incidentaloma chose to have adrenalectomy, and some chose surveillance. The relationships between clinical features were analysed with a chi-square test and rank sum test. RESULTS: In total, 634 patients with adrenal incidentaloma were studied. Their age ranged from 17 to 85 years old with a median age of 50 years. Of 478 cases with pathological results, adenoma was the most common tumour (233/478), with 84 cases of pheochromocytoma and 36 cases of adrenocortical carcinoma were 84 and 36. When the tumour size was <=4 cm, >95 % were benign; when the tumour size was >6 cm, 33 % were malignant. For patients with a tumour size <=4 cm, 249/376 cases had an adrenalectomy performed. Due to anxiety over a potential malignant transformation and enlargement, most patients (>80 %) under surveillance preferred to undergo adrenalectomy. CONCLUSIONS: Pheochromocytoma and adrenocortical carcinoma were not rare tumours of adrenal incidentaloma, and 4 cm is a good size cutoff to use in the diagnosis of an adrenal incidentaloma. Other than surveillance, laparoscopic adrenalectomy may become the method of choice for management of small adrenal incidentaloma. PMID- 27278529 TI - Hyperoxaluria-induced tubular ischemia: the effects of verapamil on the antioxidant capacity of the affected kidneys. AB - To evaluate the potential protective effects of a calcium channel blocker (Verapamil) on the oxidative stress related changes with an emphasis on the antioxidant capacity of the kidneys an experimental study in rats was performed. A total of 44 rats have been included. Hyperoxaluria was induced in Group 1 by continuous administration of ethylene glycol (EG). Animals in Group 2 received Verapamil in addition to EG. Animals in Group 3 constituted the control group. In addition to the evaluation of tissue and serum levels of three scavenging enzymes, NO, MDA and T-AOC; the presence and degree of crystal formation in renal parenchyma were evaluated in all animals after 7 and 28 days. Our data demonstrated that in addition to the lower level of all three scavenging enzymes (SOD, CAT and GSH) particularly during late phase evaluation (4 weeks); the total antioxidant capacity (T-AOC) of these kidneys were also higher when compared with the animals receiving EG only. Tissue and serum levels of both NO and MDA indicated the preventive effect of Verapamil on the oxidative stress induced changes. Very limited or no crystallization in the kidneys treated with verapamil during early and late phase examination was observed when compared with considerable crystal formation in Group 2 animals. Verapamil treatment may preserve the oxidant capacity of the kidneys and subsequently limit the crystal deposition induced by hyperoxaluria. Verapamil could therefore be considered in the management of kidney stone formation particularly in cases with recurrent kidney stone disease. PMID- 27278530 TI - Proximal junctional kyphosis and failure-diagnosis, prevention, and treatment. AB - Technical advancements have enabled the spinal deformity surgeon to correct severe spinal mal-alignment. However, proximal adjacent segment pathology (ASP) remains a significant issue. Examples include proximal junctional kyphosis (PJK) and proximal junctional failure (PJF). Agreement on the definition, classification, and pathophysiology of PJK and PJF remains incomplete, and an understanding of the risk factors, means of prevention, and treatment of this problem remains to be elucidated. In general, PJK is a relatively asymptomatic radiographic diagnosis managed with patient reassurance and monitoring. On the other hand, PJF is characterized by mechanical instability, pain, and more severe kyphosis, with potential for neurologic compromise. Patients who develop PJF more often require revision surgery than those with PJK. This chapter will review the current understanding of PJK and PJF. PMID- 27278531 TI - Impact of spine surgery complications on costs associated with management of adult spinal deformity. AB - A better understanding of the consequences of spine surgery complications is warranted to optimize patient-reported outcomes and contain the rising health care costs associated with the management of adult spinal deformity (ASD). We systematically searched PubMed and Scopus databases using keywords "adult spinal deformity surgery," "complications," and "cost" for published studies on costs of complications associated with spinal surgery, with a particular emphasis on ASD and scoliosis. In the 17 articles reviewed, we identified 355,354 patients with 11,148 reported complications. Infection was the most commonly reported complication, with an average treatment cost ranging from $15,817 to $38,701. Hospital costs for patients with deep venous thrombosis, pulmonary thromboembolism, and surgical site infection were 2.3 to 3.1 times greater than for patients without those complications. An effort to collect and characterize data on cost of complications is encouraged, which may help health care providers to identify potential resources to limit complications and overall costs. PMID- 27278532 TI - [Not Available]. PMID- 27278533 TI - [Not Available]. PMID- 27278534 TI - [Not Available]. PMID- 27278535 TI - [Not Available]. PMID- 27278536 TI - A comparative study on the complications of conventional and end-to-side inserting pancreatojejunostomy after pancreaticoduodenectomy. AB - PURPOSE: Pancreatico-digestive anastomosis is important in ensuring the safety of pancreaticoduodenectomy. This study compared the postoperative complications of a newly developed method of inserting end-to-side pancreaticojejunostomy with the conventional pancreaticojejunostomy after pancreaticoduodenectomy. METHODS: From April 2012 to December 2015, 108 consecutive patients underwent pancreaticoduodenectomy at Kumamoto University Hospital. A modified child's reconstruction was performed with the inserting or conventional pancreaticojejunostomy. The clinical course and the incidence of postoperative complications were retrospectively evaluated. RESULTS: Five patients were excluded, four who underwent hepato-pancreatoduodenectomy and one who did not require pancreaticojejunostomy because of an atrophic pancreatic remnant. Of the 103 patients that were included in the analysis, 41 and 62 underwent surgery with the inserting and conventional methods, respectively. The incidence of postoperative Clavien-Dindo grade > II complications was similar in the two groups [36.6 % (15/41) vs 27.4 % (17/62)]. However, the rates of grade C postoperative pancreatic fistula [7.3 % (3/41) vs 0 % (0/62) P = 0.030] and re operation for postoperative complications [14.6 % (6/41) vs 3.2 % (2/62), P = 0.034] were significantly higher in the inserting group than in the conventional group. There were no in-hospital deaths in either group. CONCLUSIONS: The conventional pancreaticojejunostomy is safer than the end-to-side inserting pancreaticojejunostomy, as the latter is associated with a risk of severe complications. Improvements in pancreatico-digestive anastomosis techniques are required. PMID- 27278537 TI - Inhibition of DACH1 activity by short hairpin RNA represses cell proliferation and tumor invasion in pancreatic cancer. AB - Cancer of the pancreas is one of the most lethal diseases worldwide. Better understanding of the molecular mechanisms involved in tumorigenesis is of great consequence to elevate the survival rate. Human Dachshund homologue 1 (DACH1) plays a controversial role in human malignancy progression with its expression being altered in a variety of cancers. Nevertheless, its functional roles and molecular mechanisms in pancreatic cancer remain unknown. The expression of DACH1 in pancreatic cancer cell lines and the ductal epithelial cells were evaluated both at mRNA and protein levels. Three pairs of siRNA targeting the DACH1 gene were designed and synthesized, double-stranded short hairpin RNA (shRNA) were annealed and inserted into pGenesil-1 vector, which was confirmed by enzymatic digestion and sequencing analyses. The successfully constructed recombinant plasmids were transfected into Capan-1 cells and our data indicated that knockdown of DACH1 gene expression showed strong correlation with repressing tumorigenesis. The proliferation of Capan-1 cells was significantly repressed as evaluated by CCK-8 and colony formation assays. Flow cymetry revealed that cell apoptosis was promoted in interference plasmid group compared with control groups (P<0.05), whereas cell cycle had no significant differences among the groups (P>0.05). Transwell assay validated the abilities of migration and invasion as being significantly reduced in pshRNA-DACH1 group. Furthermore, our study suggested that DACH1 expression regulates the pancreatic cancer cell apoptosis through interacting with Bcl-2 signaling axis, whereas it controls cell migration and invasion via epithelial-mesenchymal transition (EMT) process. PMID- 27278538 TI - Imaging to guide transcatheter aortic valve implantation. AB - This review article summarizes the value of multi-modality imaging, including 3 dimensional transesophageal echocardiography, for patient selection, procedural guidance, and follow-up of transcatheter aortic valve implantation. PMID- 27278539 TI - Quantitative measurements of aortic valve coaptation by three-dimensional transesophageal echocardiography in patients with aortic regurgitation without primary leaflet disease. AB - BACKGROUND: Aortic regurgitation (AR) without primary leaflet disease (functional AR) is known to occur as a result of loss of coaptation due to sinotubular junction (STJ) dilatation. However, the characteristics of change in the aortic valve coaptation length (AVCL) in 3 cusps in patients with functional AR are, as yet, unclear. The aim of this study was to measure the AVCL in 3 cusps in patients with functional AR by three-dimensional transesophageal echocardiograph (3D TEE). METHODS AND RESULTS: Thirteen patients with functional AR with or without aortic dilatation (trivial to mild AR [group A] and moderate to severe AR [group B]) and 7 controls without AR (group N) were examined. We measured the AVCL between the left coronary cusp (LCC) and right coronary cusp (RCC), the LCC and non coronary cusp (NCC), the RCC and NCC, and we also measured the cusp projection area, STJ arc length, leaflet tip-Valsalva wall distance and inter commissural distance in each cusp by 3D TEE. The average AVCL was significantly shorter in group B than in groups N and A (P < 0.001). Particularly, in group B, there was a significant difference in AVCL in the 3 cusps (P = 0.043). Moreover, although there were no significant differences in the size of cusps in groups N and A, there was disproportion in the size of those cusps in group B with the largest in RCC. CONCLUSION: Cusp enlargement was not uniform and was greatest in the RCC, and the loss of coaptation between the 3 cusps was also not uniform, with predominant reduction in the coaptation between the RCC and the other 2 cusps. PMID- 27278541 TI - Cardiac tamponade during transesophageal echocardiography in a patient with infective endocarditis. AB - An 81-year-old man with a history of diabetes mellitus and end-stage renal disease was admitted because of infective endocarditis. During transesophageal echocardiography (TEE), pericardial effusion rapidly increased and led to cardiac tamponade. Despite intensive therapy, the patient did not recover. Autopsy showed hemopericardium, ruptured sinus of Valsalva, and vegetation on the aortic valve. Our case suggests that cardiac tamponade due to the rupture of a sinus of Valsalva can occur in patients with aortic valve endocarditis complicated by perivalvular abscess. Therefore, we must be aware of this devastating complication and take preventive measures when performing TEE in such patients. PMID- 27278540 TI - Increased mid-left ventricular rotation in patients with Duchenne muscular dystrophy using two-dimensional speckle tracking echocardiography. AB - BACKGROUND: In patients with Duchenne muscular dystrophy (DMD), cardiomyopathy initially occurs during adolescence. In routine echocardiographic examination, we often recognize increased rotational movement of the left ventricle in DMD patients even if their conventional echocardiographic finding is normal. Two dimensional speckle tracking echocardiography can assess left ventricular (LV) rotation. The aim of this study was to analyze the mid-LV rotation and to investigate the clinical implication of this abnormal movement. METHODS: Nineteen DMD patients (age 15.5 +/- 3.1 years) and 22 age-matched healthy subjects were recruited. The two-dimensional speckle tracking method was used to determine the mid-LV rotation at the papillary muscle level. The mid-LV rotation and rotational velocity were calculated and were compared with other echocardiographic data and indices of autonomic function. RESULTS: Total rotation was greater in the DMD group than in the normal group (7.3 +/- 1.4 degrees versus 5.2 degrees +/- 1.3 degrees , p < 0.05). Both peak diastolic clockwise and counterclockwise rotational velocity were greater in the DMD group (p < 0.005 and p < 0.05, respectively). Time from the second heart sound to peak diastolic clockwise rotation (% diastolic duration) was greater in the DMD group (p < 0.005). Total rotation and percentage of adjacent normal R-R intervals more than 50 ms different showed a negative correlation (r = -0.72) in the DMD group. CONCLUSION: In DMD patients, cases diagnosed with normal LV fractional shortening showed an increase in mid-LV rotation that might be due to relative increase of sympathetic nervous function before global cardiac function decreases. PMID- 27278542 TI - Parachute mitral valve incidentally diagnosed in an adult patient with hypertension. AB - We describe a 52-year-old woman incidentally diagnosed as having parachute mitral valve (PMV). Echocardiography displayed a parachute-like deformity of the mitral valve characterized by a unifocal attachment of mitral valve chordae. PMV is a congenital cardiac malformation that causes stenosis of the mitral valve and is often found in combination with left-heart obstruction in the pediatric population. The incidence of PMV in adults is extremely low. This patient had no related cardiac complications, which accounts for the long asymptomatic period. Thus, rare forms of congenital heart disease in late adulthood need attention in echocardiographic study. PMID- 27278543 TI - Inverted left atrial appendage presenting as a large left atrial mass. AB - Inverted left atrial appendage (ILAA) is a rare phenomenon. We describe a patient with mitral stenosis who presented with a homogenous mass in the left atrium, mimicking a large thrombus. The patient was sent to surgery and no thrombus was found; intraoperative examination by the surgeon revealed an ILAA. We briefly discuss the main features of this entity and also some aspects of the differential diagnosis. PMID- 27278544 TI - Sustaining Chicago's Informal Caregivers: an Age-Friendly Approach. AB - The concept of age-friendliness has been globally coined by the World Health Organization (WHO) to give value to the physical, social, and environmental factors that can promote or hinder older residents' ability to age in place in cities. The initiative has been very successful in raising awareness among public health policy makers about the generic needs of older adults and urban features that promote active aging. However, the movement has been less focused on highlighting divergent needs of different older adult populations and their informal caregivers. The objective of this mixed method study is to analyze the ratings of 397 caregivers of urban age-friendly features relative to the ratings of 1737 noncaregivers collected as part of a baseline assessment of the age friendliness of the city of Chicago. Using the approved WHO Vancouver Protocol, the research team also conducted six mixed caregiver/noncaregiver focus groups (n = 84) and three caregiver-only focus groups (n = 21). Survey findings show that informal caregivers rate all eight age-friendly domains with less satisfaction than do noncaregivers. Discussion in focus groups highlighted some of the reasons for these less favorable ratings and foregrounded the domains and themes that mattered most to caregivers. In conclusion, while our study revealed few systematic differences between caregiver and noncaregiver survey satisfaction ratings, caregivers report significantly poorer health than do noncaregivers. In addition, caregiver-only focus groups foregrounded "missing" priority issues specific to caregivers such as respite and the quality of training and flexibility of home help care. Results suggest that one productive next step for researchers would be to widen the usual range of factors considered essential for maintaining the well-being of informal caregivers of community-dwelling older adults. The age-friendly domains provide a starting point for this. Another would be to develop integrated support and improve service responsiveness to particular caregiver/care recipient dyad's physical, psychological, and social needs. PMID- 27278545 TI - Breaking the Silence: Recognizing Sexual Violence in Criminal Justice Reform. PMID- 27278546 TI - Rapid and Sensitive Differentiating Ischemic and Hemorrhagic Strokes by Dried Blood Spot Based Direct Injection Mass Spectrometry Metabolomics Analysis. AB - Cerebral infarction (CI) and intracerebral hemorrhage are lethal cerebrovascular diseases, sometimes sharing similar clinical manifestations but with distinct therapeutic strategies. Delayed treatment usually resulted in poor prognosis. A timely diagnosis report is highly warranted especially in emergency. One hundred twenty-nine CI patients, 73 intracerebral hemorrhage (ICH) patients, and 98 controls were enrolled in this study. A direct injection mass spectrometry metabolomics approach was adopted using dried blood spot samples. This targeted metabolomics analysis focused on absolute quantitation of 23 amino acids, 26 carnitine/carnitine esters, and 22 calculated ratios parameters. Compared to the normal control group, CI and ICH showed distinct metabolite changes, respectively. For stroke differentiation, Tyr, C5-OH/C0, Cit, Asn, Pro, Val, Arg/Orn, Leu, and Val/Phe were elevated in the CI group. On the contrary, C5:1, Phe/Tyr, (C0 + C2 + C3 + C16 + C18:1)/Cit, and Met/Leu were of lower levels in the CI group. Using regression model based on some of the above-mentioned parameters, 79.07% of stroke patients from a new set could be definitely confirmed. This study proved the targeted metabolomics analysis was a promising tool for rapid and timely stroke differentiation. PMID- 27278547 TI - Use of Western Neuropsychological Test Battery in Detecting HIV-Associated Neurocognitive Disorders (HAND) in Zambia. AB - This is a study of neuroAIDS in sub-Saharan Africa, involving 266 Zambian adults infected with the human immunodeficiency virus (HIV), clade C. All HIV+ participants were receiving combination antiretroviral therapy (CART), and were administered a comprehensive neuropsychological (NP) test battery covering seven ability domains that are frequently affected by neuroAIDS. The battery was developed in the U.S. but has been validated in other international settings and has demographically-corrected normative standards based upon 324 healthy Zambian adults. Compared to the healthy Zambian controls, the HIV+ sample performed worse on the NP battery with a medium effect size (Cohen's d = 0.64). 34.6 % of the HIV+ individuals had global NP impairment and met criteria for HIV associated neurocognitive disorder (HAND). The results indicate that the Western-developed NP test battery is appropriate for use in Zambia and can serve as a viable HIV and AIDS management tool. PMID- 27278548 TI - A Self-Reported Adherence Measure to Screen for Elevated HIV Viral Load in Pregnant and Postpartum Women on Antiretroviral Therapy. AB - Maternal adherence to antiretroviral therapy (ART) is a concern and monitoring adherence presents a significant challenge in low-resource settings. We investigated the association between self-reported adherence, measured using a simple three-item scale, and elevated viral load (VL) among HIV-infected pregnant and postpartum women on ART in Cape Town, South Africa. This is the first reported use of this scale in a non-English speaking setting and it achieved good psychometric characteristics (Cronbach alpha = 0.79). Among 452 women included in the analysis, only 12 % reported perfect adherence on the self-report scale, while 92 % had a VL <1000 copies/mL. Having a raised VL was consistently associated with lower median adherence scores and the area under the curve for the scale was 0.599, 0.656 and 0.642 using a VL cut-off of >=50, >=1000 and >=10000 copies/mL, respectively. This simple self-report adherence scale shows potential as a first-stage adherence screener in this setting. Maternal adherence monitoring in low resource settings requires attention in the era of universal ART, and the value of this simple adherence scale in routine ART care settings warrants further investigation. PMID- 27278550 TI - A case of BK virus nephropathy without hemorrhagic cystitis after hematopoietic stem cell transplantation. PMID- 27278549 TI - Factors Associated with Sexual Risk of HIV Transmission Among HIV-Positive Latino Men Who have Sex with Men on the U.S.-Mexico Border. AB - We present results from a cross-sectional, clinic-based survey of border-region Latino men who have sex with men (MSM) and who also are living with HIV in the El Paso-Ciudad Juarez area. Among the 66 participants who reported serodiscordant anal or vaginal intercourse, we examined levels of psychological distress and substance use and the association of these variables with condomless sex. Bivariate analyses indicated that MSM who reported condomless sex with a serodiscordant partner were more likely to report higher scores on measures of anxiety, depression, and trauma. These men were also more likely to report more days of alcohol use to the point of intoxication. In multivariate logistic regression, no variables were independently associated with sexual risk behavior, but symptoms of anxiety trended toward statistical significance. Our study is one of few reports aimed at understanding the HIV epidemic among Latino MSM living with HIV in the El Paso-Ciudad Juarez border region. Although we found no evidence of a relation between our measures of psychological distress and substance use and sexual risk behavior in multivariate analyses, psychological distress and problematic alcohol use were common in the sample and are important targets for intervention in their own right. PMID- 27278551 TI - Colorectal surgery in Italy. Criteria to identify the hospital units and the tertiary referral centers entitled to perform it. AB - Improving the quality and effectiveness of care is a key priority of any health policy. The outcomes of health care can be considered as indicators of effectiveness or quality. The scientific literature that evaluates the association between the volume of activity and the outcome of health interventions has greatly developed over the past decade, but, for practical reasons, ethical and social issues, a few randomized controlled studies were made to evaluate this association, although there are numerous observational studies of outcome and systematic reviews of the studies themselves. The colorectal surgery is the most studied area and it represents the ideal testing ground to determine the effectiveness of the quality indicators because of the high incidence of the disease and the wide spread in the territory of the structures that aim to tackle these issues. Numerous studies have documented an association between the large number of colo-rectal surgical procedures and the quality of results. In particular, the volume of activity is one of the characteristics of measurable process that can have a significant impact on the outcome of health care. In conclusion, the ability to use volume thresholds as a proxy for quality is very tempting but it is only part of reality. Infact, the volume-outcome relationship strictly depends on the type of cancer (colon vs rectum) and it appears somehow stronger for the individual surgeon than for the hospital; especially for the 5-year overall survival, operative mortality and number of permanent stoma. PMID- 27278552 TI - A genome wide analysis of alternative splicing events during the osteogenic differentiation of human cartilage endplate-derived stem cells. AB - Low back pain is a prevalent disease, which leads to suffering and disabilities in a vast number of individuals. Degenerative disc diseases are usually the underlying causes of low back pain. However, the pathogenesis of degenerative disc diseases is highly complex and difficult to determine. Current therapies for degenerative disc diseases are various. In particular, cell-based therapies have proven to be effective and promising. Our research group has previously isolated and identified the cartilage endplate-derived stem cells. In addition, alternative splicing is a sophisticated regulatory mechanism, which greatly increases cellular complexity and phenotypic diversity of eukaryotic organisms. The present study continued to investigate alternative splicing events in osteogenic differentiation of cartilage endplate-derived stem cells. An Affymetrix Human Transcriptome Array 2.0 was used to detect splicing changes between the control and differentiated samples. Additionally, molecular function and pathway analysis were also performed. Following rigorous bioinformatics analysis of the data, 3,802 alternatively spliced genes were identified, and 10 of these were selected for validation by reverse transcription-polymerase chain reaction. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analysis also revealed numerous enriched GO terms and signaling pathways. To the best of our knowledge, the present study is the first to investigate alternative splicing mechanisms in osteogenic differentiation of stem cells on a genome-wide scale. The illumination of molecular mechanisms of stem cell osteogenic differentiation may assist the development novel bioengineered methods to treat degenerative disc diseases. PMID- 27278553 TI - Influence of doxorubicin on apoptosis and oxidative stress in breast cancer cell lines. AB - Breast cancer is one of the leading causes of mortality among women worldwide due to aggressive behavior, early metastasis, resistance to existing chemotherapeutic agent and high mortality rate. Doxorubicin (Dox) is a powerful antitumoral drug. It is one of the most active agents for treatment of breast cancer. The aim of the present study was to evaluate the influence of Dox in apoptosis and oxidative stress in the breast cancer cell lines MCF-10F, MCF-7 and MDA-MB-231. These studies showed that Dox decreased anti-apoptotic Bcl-2 protein expression and affected oxidative stress by increasing hydrogen peroxide production and simultaneously decreasing NF-kappaB gene and protein expression in MCF-7, a tumorigenic triple-positive cell line. Results also indicated that Dox induced apoptosis by upregulating Bax, caspase-8 and caspase-3 and downregulation of Bcl 2 protein expression. On the contrary, ROS damage decreased by increasing SOD2 gene and protein expression and hydrogen peroxide production with parallel NF kappaB protein expression decrease in MDA-MB-231, a tumorigenic triple-negative breast cancer cell line. It can be concluded that Dox activated apoptosis by inducing proteolytic processing of Bcl-2 family, caspases and simultaneously decreased oxidative stress by influencing ROS damage in MCF-7 and MDA-MB-231 cell lines. PMID- 27278554 TI - Effects of combining erlotinib and RNA-interfered downregulation of focal adhesion kinase expression on gastric cancer. AB - OBJECTIVE: To investigate the synergistic effects of combining erlotinib and RNA interference downregulation of focal adhesion kinase (FAK) expression on the proliferation, apoptosis, invasion and migration of the human gastric adenocarcinoma cell line AGS. METHODS: Cells were divided into five experimental groups: Group A, nontransfected control; Group B, transfected with empty vector; Group C, transfected with FAK-shRNA; Group D, erlotinib treatment; Group E, combination erlotinib treatment and transfected with FAK-shRNA. FAK protein levels were confirmed via Western blotting. Cell proliferation (CCK-8 assay, apoptosis (flow cytometry), cell invasion (transwell assay) and migration (scratch assay) were evaluated. RESULTS: RNA interference significantly decreased FAK protein levels. Cell proliferation, invasion and migration were significantly lower in Groups C, D and E compared with Group A, and significantly lower in Group E than in Groups C and D. CONCLUSIONS: RNA interference effectively silences FAK expression and inhibits malignant cell proliferation and invasion in gastric cancer cells. The effect of FAK inhibition is increased by co-treatment with erlotinib. PMID- 27278555 TI - Distance from Dura mater to spinal cord at the thoracic vertebral level: An introductory study on local subdural geometry for thoracic epidural block. AB - OBJECTIVE: To evaluate the anatomical safety margins in relation to thoracic epidural block by analysing magnetic resonance (MR) images. METHODS: This retrospective study identified consecutive patients who underwent MR imaging of the thoracic vertebral spine. The distance from the dura mater to the spinal cord (DTC) was measured at different thoracic intervertebral levels using three different pathways as references: the 'U', 'L' and 'M' lines. RESULTS: A total of 346 patients provided MR images for analysis. The vertical DTC was the longest at the T5/6 intervertebral level (mean +/- SD: 4.22 +/- 1.43 mm) and the shortest at the T11/12 intervertebral level (mean +/- SD: 2.51 +/- 0.87 mm). The DTC was the longest on the 'L' line at the T1/2 and T5/6 intervertebral levels and on the 'U' line at the T10/11 intervertebral level. The difference in DTC between the 'U' and 'L' lines was the greatest at the T5/6 intervertebral level. CONCLUSION: Differences in the DTC were observed among the thoracic intervertebral levels. The variability of the safety margin according to the angle of needle insertion was the largest at the T5/6 intervertebral level. PMID- 27278557 TI - Abdominal ultrasound in 2008. PMID- 27278556 TI - Proprotein convertase subtilisin/kexin type 9 levels and aortic valve calcification: A prospective, cross sectional study. AB - OBJECTIVE: To investigate the possible association between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and the incidence and severity of calcific aortic valve disease (CAVD). METHODS: This prospective, cross sectional study involved patients with and without (controls) aortic valve calcification diagnosed by transthoracic echocardiography and dual source computed tomography (DSCT) scan. Aortic valves calcification scores were calculated from DSCT scans and patients were graded: grade 1, no calcification; grade 2, mildly calcified; grade 3, moderately calcified; grade 4, heavily calcified. Plasma PCSK9 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Forty patients were grade 1 (controls), 32 were grade 2, 48 were grade 3 and 32 were grade 4. Plasma levels of PCSK9 were significantly different between the four groups and the highest value was observed in the patients with grade 2 calcification. Only low-density lipoprotein cholesterol and lipoprotein (Lp)(a) were associated with the severity of CAVD. Regression analysis showed that age, Lp(a) and PCSK9 were independent predictors of CAVD. CONCLUSION: Data from this cross sectional study in a small sample of patients showed that plasma PCSK9 was correlated with the presence of CAVD but not its severity. PMID- 27278558 TI - Accelerating effects of ultrasonic thrombolysis with bubble liposomes. AB - PURPOSE: The accelerating effect on thrombolysis by combined use of 500-kHz low frequency ultrasound (US), recombinant tissue plasminogen activator (rt-PA), and bubble liposomes (BLs) was verified in vitro. METHODS: A fibrin clot was formed by adding thrombin to bovine plasma. It was enclosed in a pressurized container, the pressure and temperature of which were maintained at 150 mmHg and 37 degrees C, respectively. Ultrasonic conditions were set at a continuous wave, a frequency of 500 kHz, an intensity of 0.7 W/cm(2), and a sonication time of 60 s. We derived the rate of reduction in clot weight from the decreased clot weight and the weight before sonication. We compared the rate of reduction in groups combining physiological saline, rt-PA, BLs, and US. RESULTS: Only the rt-PA+US+BL group showed a significantly accelerated thrombolytic effect compared with any other group or with any combination of two factors in the 60-s period (0.001 < P < 0.027). CONCLUSION: BLs have great potential to accelerate the thrombolytic effect of rt-PA with low-frequency, 500-kHz, continuous-wave ultrasound. PMID- 27278559 TI - Preliminary study of contrast-enhanced harmonic endosonography with second generation contrast agents. AB - PURPOSE: We developed a novel echoendoscope that enables contrast harmonic imaging using ultrasound contrast agents and performed contrast-enhanced harmonic endosonography (EUS) both in vitro and in vivo. METHODS: An experimental convex array echoendoscope equipped with a wideband transducer and a specific mode for contrast harmonic imaging was used. A Doppler phantom model was employed in in vitro experiments to determine the optimal mechanical indices for contrast harmonic imaging by the echoendoscope. In the in vivo experiments, the echoendoscope was inserted into the stomachs of dogs. The digestive organs were observed after intravenous infusion of a contrast agent, Definity, using contrast enhanced harmonic EUS. Two patients, one with pancreatic carcinoma and one with a gastrointestinal stromal tumor (GIST), underwent contrast-enhanced harmonic EUS. RESULTS: In vitro experiments revealed that the optimal mechanical indices were 0.35-0.40 for intermittent imaging and 0.30 or less for real-time imaging. In the in vivo experiments, branching vessels and subsequent homogeneous distribution of the signal in the pancreatic tissue were observed. During clinical application, typical vascular patterns were observed in pancreatic carcinoma and a GIST. CONCLUSION: Contrast-enhanced harmonic EUS visualized parenchymal perfusion and the fine vascular structure in digestive organs and should be a useful and powerful method for clinical investigations. PMID- 27278560 TI - Hemodynamic evaluation by endoscopic ultrasonography of esophageal varices resistant to injection sclerotherapy. AB - PURPOSE: Some esophageal variceal cases are resistant to endoscopic injection sclerotherapy (EIS) using 5% ethanolamine oleate (5% EO). We evaluated the hemodynamics of esophageal varices that were resistant to EIS using 5% EO. METHODS: Selected for this study were 290 consecutive patients who underwent hemodynamic evaluation using endoscopic color Doppler ultrasonography (ECDUS) and an ultrasonic microprobe (UMP) before EIS. EIS was performed using 5% EO with iopamidol (5% EOI) under fluoroscopy. We retrospectively evaluated the hemodynamic differences between patients resistant to and not resistant to EIS using 5% EOI. RESULTS: Nine patients were resistant to EIS using 5% EOI (group A). Various parameters were compared between the 281 patients who had been given EIS using 5% EOI for esophageal varices (group B) and the 9 patients in group A. The mean number of EIS treatments until shrinkage of esophageal varices was achieved in group A (6.8 +/- 3.4) was significantly greater than that in group B (4.4 +/- 2.1) (P < 0.01). The mean amount of 5% EOI used in group A (31.1 +/- 17.4 ml) was significantly larger than that used in group B (14.9 +/- 8.8 ml) (P < 0.001). The mean frequency shift of esophageal varices in group A (452.9 +/- 106.6 Hz) was significantly higher than that in group B (313.0 +/- 103.2 Hz) (P < 0.001) as determined by ECDUS. The mean diameter of esophageal varices as found by UMP was 8.0 +/- 3.5 mm in group A and 4.6 +/- 2.4 mm in group B, with the difference being significant (P < 0.01). Perforating veins inflowing from extramural to intramural regions were recognized in 8 (88.9%) of the 9 patients in group A and in 67 (24.1 %) of the 281 patients in group B. The mean diameter of the perforating vein was 3.8 +/- 1.9 mm in group A and 2.1 +/- 0.5 mm in group B, as shown by UMP, a difference that was statistically significant (P < 0.01). CONCLUSION: Hemodynamic evaluation revealed that the esophageal varices were of a higher grade in group A than in group B. By using ECDUS and UMP, this study shed light on the hemodynamics of esophageal variceal cases resistant to EIS using 5% EOI. PMID- 27278561 TI - Ultrasonograms showing multiple myeloma in the skull. PMID- 27278562 TI - Congenital absence of the horizontal portion of the left portal vein. PMID- 27278563 TI - Intrarenal pseudoaneurysm with renal cell carcinoma. PMID- 27278564 TI - Criteria for ultrasound diagnosis of deep venous thrombosis of lower extremities. PMID- 27278565 TI - Three-Dimensional Imaging of Urethral Stricture Disease and Urethral Pathology for Operative Planning. AB - Diagnosing urethral pathology can prove difficult, as clinically, the presentation is often nonspecific and may be suggestive of multiple etiologies. Therefore, detailed and accurate urethral imaging in both males and females is critical. Since the early 1900s, conventional imaging studies including RUG and VCUG, with adjunct cystourethroscopy, have remained the gold standard diagnostic techniques to evaluate urethral pathology. However, limitations of conventional imaging have generated interest in finding alternative imaging modalities with comparable, if not superior, diagnostic accuracy, the goal being a more complete assessment of urethral pathology and anatomy that would allow for appropriate surgical planning. Imaging modalities with three-dimensional (3D) capabilities may provide more comprehensive information regarding urethral diseases through a more detailed illustration of periurethral soft tissue structures. Whether or not these imaging modalities will replace conventional studies is unclear, though there is an increasing body of literature that support their use. PMID- 27278566 TI - Analysis of Internet Suicide Pacts Reported by the Media in Mainland China. AB - BACKGROUND: In mainland China, frequent Internet suicide pacts in recent years have raised strong concerns from several social sectors and the influence of social networks on suicide is constantly growing. AIMS: To identify the epidemiological characteristics of media-reported Internet suicide pacts in mainland China. METHOD: Our study comprised 62 Internet suicide pacts involving 159 victims in mainland China before June 1, 2015. Kendall's randomness test, a trend test, and a circular distribution test were applied to identify the rising or concentrated trends in the time of occurrence of Internet suicide pacts. RESULTS: The overall male-to-female ratio was 2.3:1. Suicide victims were mainly people in their 20s to 30s (84.1%). In all, 87.1% suicide victims completed suicide in sealed hotels or rental housing, and charcoal-burning suicide accounted for 80.6% of cases. CONCLUSION: People who complete suicide as part of an Internet suicide pact are more likely to be males, aged 20-30 years. Charcoal burning suicide in sealed hotels or rental housing was the commonest way of dying. PMID- 27278567 TI - Cluster Analysis of Characteristics of Persons Who Died by Suicide in the Montreal Metro Transit. AB - BACKGROUND: Suicides occur in metro systems worldwide and patterns vary in different urban transit networks. AIMS: This study presents an in-depth analysis of 117 suicides in the Montreal Metro from 2000 to 2008 based on data obtained from coroners' investigations. METHOD: Cluster analyses were performed to identify characteristics of groups of people who kill themselves in the Montreal Metro. We also compared changes in characteristics with data from 1986 to 1995. RESULTS: We identified five clusters of suicidal persons that describe patterns of characteristics of individuals who died by suicide in the metro that may be useful for prevention. Comparisons of suicides during 2000-2008 with data from a previous study of coroners' investigations of Montreal Metro suicides during 1986 1995 indicate changes in age, isolation, types of problems, and geographic patterns. CONCLUSION: Characteristics of metro suicides may be specific to localities and can change over time. Their understanding may facilitate the development of prevention strategies tailored to these different profiles. PMID- 27278568 TI - Risk and Protective Factors for Suicidal Behaviors Among Pacific Youth in New Zealand. AB - BACKGROUND: New Zealand has the second highest youth suicide rate in the OECD and particularly among Pacific New Zealanders, who have a threefold higher risk of suicide attempt compared with the general population. AIMS: Protective and risk factors for suicide attempts among New Zealand Pacific adolescents were assessed using data from Youth'12, an adolescent health and well-being survey. METHOD: This randomly selected nationally representative sample of New Zealand secondary school students included 1,445 Pacific high school students aged 12-17 years. RESULTS: One in 10 (11.6%) Pacific adolescents reported attempting suicide. Risk factors for suicide included: being female, household food insecurity, low levels of family connections and family monitoring, life dissatisfaction, having a religious affiliation, and previous suicide by a family member or friend. Of those who had made a suicide attempt, 71% also experienced both suicide ideation and self-harm. CONCLUSION: This study suggests that given the high rates of suicide ideation and attempts among Pacific young people, targeted trials for new ways of support should be prioritized for this high-risk group. The Pacific family environment, which continues to be the critical space for intervening, and the school environment, as a provider of health services, were both protective of suicide attempt. PMID- 27278569 TI - Prevention of Suicidal Behavior in Prisons. AB - BACKGROUND: Worldwide, prisoners are at high risk of suicide. Research on near lethal suicide attempts can provide important insights into risk and protective factors, and inform suicide prevention initiatives in prison. AIMS: To synthesize findings of research on near-lethal attempts in prisons, and consider their implications for suicide prevention policies and practice, in the context of other research in custody and other settings. METHOD: We searched two bibliographic indexes for studies in any language on near-lethal and severe self harm in prisoners, supplemented by targeted searches over the period 2000-2014. We extracted information on risk factors descriptively. Data were not meta analyzed owing to heterogeneity of samples and methods. RESULTS: We identified eight studies reporting associations between prisoner near-lethal attempts and specific factors. The latter included historical, prison-related, and clinical factors, including psychiatric morbidity and comorbidity, trauma, social isolation, and bullying. These factors were also identified as important in prisoners' own accounts of what may have contributed to their attempts (presented in four studies). CONCLUSION: Factors associated with prisoners' severe suicide attempts include a range of potentially modifiable clinical, psychosocial, and environmental factors. We make recommendations to address these factors in order to improve detection, management, and prevention of suicide risk in prisoners. PMID- 27278570 TI - A Pilot Study on the Efficacy of Volunteer Mentorship for Young Adults With Self Harm Behaviors Using a Quasi-Experimental Design. AB - BACKGROUND: Studies have shown that postdischarge care for self-harm patients is effective in reducing repeated suicidal behaviors. Little is known about whether volunteer support can help reduce self-harm repetition and improve psychosocial well-being. AIM: This study investigated the efficacy of volunteer support in preventing repetition of self-harm. METHOD: This study used a quasi-experimental design by assigning self-harm patients admitted to the emergency departments to an intervention group with volunteer support and treatment as usual (TAU) for 9 months and to a control group of TAU. Outcome measures include repetition of self harm, suicidal ideation, hopelessness, and level of depressive and anxiety symptoms. RESULTS: A total of 74 cases were recruited (38 participants; 36 controls). There were no significant differences in age, gender, and clinical condition between the two groups at the baseline. The intervention group showed significant improvements in hopelessness and depressive symptoms. However, the number of cases of suicide ideation and of repetition of self-harm episodes was similar for both groups at the postintervention period. CONCLUSION: Postdischarge care provided by volunteers showed significant improvement in hopelessness and depression. Volunteers have been commonly involved in suicide prevention services. Further research using rigorous methods is recommended for improving service quality in the long term. PMID- 27278572 TI - Preventing Suicide and Self-Harm. AB - BACKGROUND: Telephone helplines are considered to play an important role in preventing suicide and self-harm among callers in distress. However, inconsistency in the methods of evaluating such services has limited the firm conclusions that can be drawn. AIMS: To evaluate the efficacy of a UK-based helpline from a service user and helpline worker perspective. METHOD: Callers were asked about their mental state at the beginning and end of the call with a short questionnaire. Helpline workers were surveyed about their experiences of using the questionnaire as part of routine service provision. RESULTS: The helpline was successful at reducing suicidal and self-harming ideation. The short questionnaire method was also successfully integrated into routine practice. CONCLUSION: Evaluating the efficacy of helplines can be successfully achieved using the short questionnaire method. PMID- 27278573 TI - Systems biology. PMID- 27278571 TI - Incidence Rates of Deliberate Self-Harm in Denmark 1994-2011. AB - BACKGROUND: The validity and reliability of suicide statistics have been questioned and few nationwide studies of deliberate self-harm have been presented. AIM: To calculate rates of deliberate self-harm in Denmark in order to investigate trends and assess the reliability of hospital records. METHOD: A register study based on all individuals recorded with an episode of deliberate self-harm or probable deliberate self-harm in nationwide registers during 1994 2011. RESULTS: A substantial difference in the rates of deliberate self-harm and probable deliberate self-harm was noted for both genders. The average incidence rate of deliberate self-harm for women and men was 130.7 (95% CI = 129.6-131.8) per 100,000 and 86.9 (95% CI = 86.0-87.8) per 100,000, respectively. The rates of deliberate self-harm for women increased from 137.6 (95% CI = 132.9-142.3) per 100,000 in 1994 to 152.7 (95% CI = 147.8-157.5) in 2011. For a subgroup of younger women aged 15-24 years, an almost threefold increase was observed, IRR = 2.5 (95% CI = 2.4-2.7). The most frequently used method was self-poisoning. CONCLUSION: The rates of deliberate self-harm and probable deliberate self-harm differed significantly. An increased incidence of deliberate self-harm among young Danish women was observed, despite detection bias. An improved registration procedure of suicidal behavior is needed. PMID- 27278574 TI - Determination of peripheral color signal density using contrast-enhanced color Doppler ultrasonography in diffuse liver disease. AB - PURPOSE: The study aimed to quantify hepatic vascular changes that accompany the development of chronic liver disease using contrast-enhanced color Doppler ultrasonography and histopathological examination. METHODS: A series of 62 patients with biopsy-proven chronic liver disease (31 chronic hepatitis, 31 liver cirrhosis) and 8 healthy controls were studied. Altogether, 22 livers (9 chronic hepatitis, 13 liver cirrhosis) obtained at surgery or autopsy were subjected to histopathological examination. Patients with cardiopulmonary disease or intrahepatic tumors were excluded. Intrahepatic color Doppler signals were scanned and counted at the liver surface in a 10 * 30 mm rectangle from liver segment V using color Doppler sonography (SSA 380 A) before and after contrast enhancement with SHU 508A (Levovist). Small arteries 30-1000 um in diameter were counted on the histopathlogical specimen by microscopy. RESULTS: The number of color Doppler signals increased significantly after contrast enhancement in both patients and controls. The number of color Doppler signals was elevated before and after contrast enhancement when chronic liver disease was present, especially in cases of Child-Pugh grade C liver cirrhosis. Histologically, more arteries 30 125 um in diameter were present in patients with chronic hepatitis than in those with liver cirrhosis, whereas more arteries ? 125 um in diameter were present in patients with liver cirrhosis than in those with chronic hepatitis. CONCLUSION: Intrahepatic color Doppler signals are probably derived from peripheral arteries larger than 125 um in diameter, and the signal density in these arteries increases with progression of the chronic liver disease. PMID- 27278575 TI - Optimal number of image slices for reliable measurement of left ventricular volumes and ejection fraction by three-dimensional transesophageal echocardiography. AB - PURPOSE: Quantification of the left ventricular (LV) volume by three-dimensional echocardiography is accurate but time-consuming. To shorten the time required, we sought to determine the minimum number of image planes necessary to measure LV volume reliably. METHODS: We analyzed transesophageal three-dimensional echocardiographic LV data obtained by the rotational scanning method in 16 patients: 11 had ischemic heart disease, and 5 had dilated cardiomyopathy. LV volumes were calculated from 6, 10, and 30 short-axis images using the disk summation method and from 2, 4, 6, 10, 20, and 30 longitudinal images using the new average rotation method. RESULTS: LV volume varied less with the average rotation method than with the disk-summation method. The 95% limit of agreement between the 30-image and 6-image methods was 0.3% +/- 3.7% for the average rotation method, whereas it was -2.0% +/- 6.9% for the disk-summation method. The time required for analysis decreased from 12.5 +/- 2.8 min with the 30-image method to only 3.3 +/- 0.5 min for the 6-image method. CONCLUSIONS: Measurement of six longitudinal images provided reliable LV volume data, even in patients with enlarged or deformed left ventricles. The short measurement time supports the use of three-dimensional echocardiographic LV volume measurement in the clinical setting. PMID- 27278576 TI - Enhancement of stents using interference of low-frequency ultrasonic echo signals. AB - PURPOSE: We set out to enhance the imaging of stents used for coronary coarctation surgery without imaging the reticulation of the stent. Because the stent is a reticulated structure, there is a relation between ultrasound wavelength and the interstice reticulation that produces the echo. METHODS: First we performed computer simulation by ultrasound frequency of transmitted signals to analyze this relation. Then, instead of controlling the transmitted wave, we processed the returned signals through a band-pass filter because of the difficulty of controlling the transmitted waves of diagnostic ultrasound equipment. Following this, we conducted experiments on an agar gel phantom containing a stent to verify the effectiveness of this method. RESULTS: The simulation confirmed that the stent was apparent when the ultrasonic wavelength equaled the product of an integer and twice the interval of the reticulation of the stent. Application of a band-pass filter of 0.8 to 1.5 MHz to the waveform returned from the agar gel phantom containing the stent. CONCLUSIONS: The effectiveness of this method in depicting the stent was confirmed. PMID- 27278577 TI - Ultrasonography and computed tomography of extracapsular invasion in cervical lymph nodes of squamous cell carcinoma in the oral cavity. AB - PURPOSE: This study evaluates the efficacy of imaging for diagnosing extracapsular invasion by metastatic cervical lymph nodes. METHODS: The subjects were 47 patients with squamous cell carcinoma of the oral cavity examined by both ultrasonography and computed tomography. All subjects had undergone neck dissection, and histopathologic examination confirmed the presence of one or more metastatic cervical lymph nodes in each of them. RESULTS: Histopathologic examination confirmed extracapsular invasion in 25 of 48 metastatic nodes; in the remaining 23 nodes, the tumor was confined within the capsule. Average short-axis diameters of the lymph nodes of these groups differed significantly (17.4 +/- 10.6 and 12.7 +/- 4.4 mm, respectively; P = 0.046). The diagnostic sensitivity, specificity, and accuracy of ultrasonography for detecting macroscopic extracapsular invasion were 80%, 74%, and 77%, respectively. The corresponding values for computed tomography were 85%, 83%, and 84%. CONCLUSION: Diagnostic images are effective for the preoperative diagnosis of extracapsular invasion of metastatic cervical nodes of carcinoma of the oral cavity. PMID- 27278578 TI - Evaluating the regional elastic modulus of a cylindrical shell with nonuniform wall thickness. AB - PURPOSE: For noninvasive diagnosis of atherosclerosis, we attempted to evaluate the elasticity of the arterial wall by measuring small changes in thickness caused by the heartbeat. The elasticity of the arterial wall has been evaluated noninvasively by measuring the change in diameter of the artery or the pulse-wave velocity; however, there is no method for noninvasively evaluating the elasticity of the arterial wall from changes in its thickness. METHODS: Employing the phased tracking method that we developed, changes in thickness of less than 100 um were measured in each regional area, which corresponded to the diameter of the ultrasonic beam. RESULTS: The elasticity of the arterial wall could be evaluated with better spatial resolution from the change in thickness than from the change in diameter of the artery or pulse-wave velocity. We therefore propose a method for evaluating the elastic modulus of an arterial wall of nonuniform wall thickness. CONCLUSIONS: In basic experiments employing silicone rubber tubes with nonuniform wall thickness as arterial models, the elastic moduli of silicone rubber tubes were evaluated by measuring changes in wall thickness. These results confirm the value of the proposed method. PMID- 27278579 TI - Clinical application of a new method that segments the region of interest into multiple layers for RF amplitude histogram analysis in the cirrhotic liver. AB - PURPOSE: We used texture analysis in conjunction with an alternative method of analyzing the amplitude histogram using a radiofrequency (RF) signal to differentiate ultrasonograms of normal and cirrhotic livers. This method segments the region of interest (ROI) into multiple layers (sub-ROIs). In each sub-ROI of a homogeneous medium, the histogram of enveloped-amplitude of RF backscattered echoes resembles a Rayleigh distribution. Theoretically, the values of the signal to-noise ratio (SNR), skewness, and kurtosis for Rayleigh statistics are constant and independent of the mean scattering intensity, which is contributed by such undesirable effects as tissue attenuation, beam diffraction, and incident waveforms. These values, which averaged overall sub-ROI, should provide an unbiased estimator. METHODS: We studied 36 normal livers and 28 cirrhotic livers, all confirmed by clinical findings including laboratory and pathology data; the SNR, skewness, and kurtosis values of the disease groups were compared. At the same time, these values were estimated using the conventional method, which did not segment the ROI into multiple sub-ROIs. The unpaired t-test was used to determine statistical significance. RESULTS: With the new method, all values obtained from cirrhotic livers differed significantly from those obtained from normal livers, and the standard deviation of these values was smaller than those obtained using the conventional method. CONCLUSIONS: These results suggest that the new method can be used to diagnose the cirrhotic liver objectively. PMID- 27278581 TI - The Japan Society of Ultrasonics in Medicine amidst the information technology revolution. PMID- 27278580 TI - Bilayer oxidized regenerated cellulose/poly epsilon-caprolactone knitted fabric reinforced composite for use as an artificial dural substitute. AB - A novel bilayer knitted fabric-reinforced composite for potentially being used as a dural substitute was developed by solution infiltration of oxidized regenerated cellulose knitted fabric (ORC) with poly epsilon-caprolactone (PCL) solution at various concentrations ranging 10-40 g/100 mL. It was found that the density of all formulations did not differ significantly and was lower than that of the human dura. Microstructure of the samples typically comprised a bilayer structure having a nonporous PCL layer on one side and the ORC/PCL composite layer on another side. Tensile modulus and strength of the samples initially decreased with increasing PCL solution concentration for up to 20 g/100 mL and re-increased again with further increasing PCL solution concentration. Strain at break of all formulations were not significantly different. Watertight test revealed that all composites could prevent leakage at the pressure within the normal range of intracranial pressure. In vitro degradation study revealed that the weight loss percentage and change in tensile properties of all samples displayed biphasic profile comprising an initially rapid decrease and followed by a gradual decrease with incubation times afterward. Micro and macro porous channels were observed to be in situ generated in the composite layer by ORC dissolution and PCL resorption during degradation while nonporous layer remained relatively unchanged. The degradation rate was found to decrease with increasing PCL solution concentration. In vitro biocompatibility using alamar blue assay on selected samples showed that fibroblasts could attach and proliferate well at all incubation periods. PMID- 27278582 TI - Aortic valve calcification and increased stiffness of the proximal thoracic ascending aorta: association with left ventricular diastolic dysfunction and early chronic kidney disease. AB - PURPOSE: The aim of this study was to clarify the relationship between the severity of aortic valve calcification (AVC) and stiffness of the proximal thoracic ascending aorta (TAA), and to examine their influence on left ventricular (LV) function and renal function. METHODS: A total of 138 hypertensive patients including 32 with diabetes mellitus and 60 with dyslipidemia were divided into four groups based on the severity of AVC. We analyzed the elastic properties of the proximal TAA from the following strain rate indices based on tissue Doppler imaging: maximum strain rate [SR(+)], minimum SR [SR(-)], and the time between the QRS peak and the peak SR(-) of the proximal TAA (SRT). RESULTS: SR(+) and SRT were significantly greater in patients with moderate AVC than in patients with mild AVC. SRT and SR(-) were well correlated with age, peak velocity across AV, TAA wall thickness (IMC), LV diastolic function, and renal function. SRT was independently related to IMC, dyslipidemia, and LV diastolic function. CONCLUSION: The severity of AVC was correlated with the elastic properties of the proximal TAA. The SR indices are useful for assessing the relation of TAA stiffness to LV function and renal function in patients with AVC. PMID- 27278583 TI - Carotid and brachial artery intima-media thickness is related to coronary atherosclerotic burden and may also represent high cardiovascular risk in patients with normal coronary angiograms. AB - BACKGROUND: Carotid and brachial artery intima-media thicknesses (IMT) determined using B-mode ultrasonography are validated surrogate markers of the severity and extent of coronary artery disease (CAD). The markers may also reflect the general vascular atherosclerotic involvement and cardiovascular risk in patients with normal coronary arteries (NCA). We aimed to investigate the relationship of carotid artery IMT (CIMT) and brachial artery IMT (BIMT) with CAD simultaneously, and also examined whether both markers represent cardiovascular risk determined by cardiovascular risk factors in patients with NCA. METHODS: One hundred eligible patients who consecutively underwent coronary angiography under suspicion of CAD were included in this study. The patients were evaluated in terms of age, gender, and the risk factors for CAD, and their total cardiovascular risk was calculated. CIMT and BIMT measurements were performed by B-mode ultrasonography on all patients. The extent and severity of CAD were evaluated by the Gensini score, and the number of severely narrowed vessels was determined by coronary angiography. RESULTS: Sixty-three patients (47 males, 16 females) with a mean age of 62 +/- 10 years had CAD, and 37 patients (20 males, 17 females) with a mean age of 51 +/- 11 years had NCA on coronary angiography. The mean age and male ratio of patients with CAD were significantly higher as compared with the patients with NCA (p < 0.001, p = 0.035, respectively). The mean number of diseased vessels was 2.2 +/- 0.9 (median 2.0), while the mean Gensini score was 25 +/- 31 (median 14.0). The CIMT and BIMT were higher in patients with CAD than in those with NCA (0.9 +/- 0.2 vs. 0.7 +/- 0.2 mm and 0.5 +/- 0.1 vs. 0.4 +/- 0.1 mm, respectively; p < 0.001 for both). The cardiovascular risk score (CVRS) was also significantly higher in the CAD group (3.8 +/- 1.1 vs. 2.9 +/- 1.4, p < 0.001). CIMT, BIMT, and CVRS were significantly correlated with the Gensini score and number of diseased vessels. For the sensitivity and the specificity of CIMT, BIMT, and CVRS to detect the presence of CAD, the areas under the ROC curve were 0.785 (95% CI 0.687-0.883, p = 0.000), 0.842 (95% CI 0.764-0.920, p = 0.000), and 0.721 (95% CI 0.591-0.813, p = 0.001), respectively. When we compared the CVRSs between the groups, which were determined according to cutoff values for CIMT and BIMT (CIMT >=0.9 vs. <0.9 and BIMT >=0.4 vs. <0.4); among the patients with NCA, CVRSs were significantly different (3.5 +/- 0.5 vs. 2.7 +/- 1.4, p = 0.035 and 3.7 +/- 1.1 and 2.7 +/- 1.3, p = 0.073; respectively). CONCLUSION: The increases in both brachial and carotid IMT are positively correlated with the extent of CAD and the number of involved vessels, and have more predictive value for CAD than the traditional CVRS. In addition, carotid IMT is also related to high CVRS in patients with NCA, and this finding may represent general vascular involvement without coronary lesions determined by coronary angiography. PMID- 27278584 TI - Application of pulsed-wave Doppler ultrasound to exploration of the peripheral vasomotor response by gender and hand dominance. AB - PURPOSE: Laser Doppler flowmetry measures peripheral vasomotor response but fails to detect changes in vascular diameters, resistance, and heart rates. Because this response contributes to assessing sympathetic disorders and relies on the above variables to be correctly interpreted, we used pulsed-wave Doppler (PWD) ultrasound to evaluate the response and to determine whether it was affected by gender or hand dominance. METHODS: PWD was applied to bilateral deep palmar branches of the radial arteries of 22 men and 22 women, using post-inspiratory cough as the sympathetic stimulus. Pulsatility index (PI), arterial diameters, heart rates, flow velocity, and blood flow before and after sympathetic stimuli were analyzed for both groups. RESULTS: Women had a higher PI value of the radial arteries at rest; in contrast, that of men was higher after sympathetic stimuli. Blood flow velocity (V max, V max mean, and V mean) at rest was higher for men than for women. A significant difference was observed in V min after stimulus. Arterial diameters and blood flow before and after stimuli were higher for men than for women. Post-inspiratory cough caused significant diameter reduction in women but heart rate elevation in men. Hand dominance had no effect. CONCLUSIONS: This study demonstrated the suitability of PWD for detailing peripheral vasomotor response, which was affected by gender but not hand dominance. Our results suggest application of PWD to diseases with unilateral sympathetic impairment, but responses for different sexes should be treated with caution. PMID- 27278585 TI - Benefit of early abdominal ultrasonography in non-surgical patients admitted to the emergency department: a pilot study. AB - PURPOSE: Ultrasonography plays a decisive role in emergency patients. The primary aim of this study is to assess whether early emergency ultrasonography alters the length of stay. METHODS: In a prospective study, patients admitted to the emergency department were divided into two groups. The first group underwent early abdominal ultrasonography (within 24 h after admission), and the second group underwent ultrasonography after more than 24 h. The two groups were compared in terms of length of stay, age, admission diagnosis, and number of further imaging techniques used. A subgroup analysis was carried out for admission diagnosis. One hundred and forty-five patients were included in the study. RESULTS: In terms of length of stay, no difference was seen between the first group (11.7 +/- 11.4 days) and the second group (13.6 +/- 11.0 days) (p = 0.1196). In the subgroups "abdominal pain" (p = 0.0333) and "cardiopulmonary disorders" (p = 0.0207), a shorter length of stay was associated with early ultrasonography, while in the subgroup "infectious disease/fever," the early ultrasonography group was associated with a prolonged length of stay (p = 0.0211). CONCLUSION: Early ultrasonography in our setting of emergency patients with a variety of different admission diagnoses did not shorten the length of stay, but the subgroups of patients with "abdominal pain" and "cardiopulmonary disorders" might have benefited from early ultrasonography. PMID- 27278586 TI - A case of solid-pseudopapillary neoplasm, focusing on contrast-enhanced endoscopic ultrasonography. AB - We used contrast-enhanced endoscopic ultrasonography (CE-EUS) to diagnose a case of solid-pseudopapillary neoplasm (SPN) in an adult man. A 58-year-old man was referred to our hospital because of a pancreatic mass found by positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) during a medical checkup in 2009. Trans-abdominal ultrasonography revealed a 24-mm hypoechoic mass at the pancreatic tail with calcification inside. Multiphasic computed tomography (CT) showed a solid mass with delayed enhancement. EUS revealed a hypoechoic mass without lateral shadowing, and neither a septum nor cystic component was detected. CE-EUS using Sonazoid((r)) showed a hypovascular mass compared with the surrounding pancreatic parenchyma, and the inside of the mass was enhanced like an alveolus nest, suggesting pseudopapillary change. Diagnosis of a solid pseudopapillary neoplasm and a concomitant small neuroendocrine tumor was made by distal pancreatectomy. PMID- 27278587 TI - Sclerosing stromal tumor of the ovary: ultrasound elastography and MRI findings on preoperative diagnosis. AB - Sclerosing stromal tumor (SST) is a benign stromal tumor of the ovary. Preoperative diagnosis of this benign tumor mainly depends on imaging findings. Dynamic computed tomography (CT) and magnetic resonance imaging (MRI) show typical contrast enhancement of SST with peripheral enhancement in the early phase and centripetal progression in the delayed phases. We present the imaging findings of ultrasonography, ultrasound elastography, and dynamic MRI in the diagnosis of SST. Abdominal ultrasound elastography is a novel technique that depicts the stromal structure of SSTs by comparing the elasticity of the tumor and the myometrium using quantitative strain values. PMID- 27278588 TI - Neonatal distal femoral epiphyseal dislocation: an ultrasound diagnosis. AB - Traumatic epiphyseal dislocation related to birth injury is uncommon. The authors report a case of slipped distal femoral epiphysis during a breech presentation in a twin pregnancy birthing process, diagnosed by ultrasonography. This type of separation could be difficult to detect in the newborn on plain radiographs because of the non-ossification of the epiphysis. Therefore, the use of sonography is helpful to make an early and accurate diagnosis in order to avoid malunion and deformities of the affected limb. Through this case report we will see the diagnostic value of high-resolution ultrasonography in diagnosing newborn injuries of the limbs, and particularly in the diagnosis of radiographically occult epiphyseal separation. PMID- 27278590 TI - Mucin-producing gallbladder carcinoma. PMID- 27278589 TI - Comparison of ultrasound speed in articular cartilage measured by different time of-flight methods. AB - The purpose of this study was to investigate whether different time-of-flight (TOF) methods including amplitude-related methods, which determine tissue borders from the reflected wave itself, and the cross-correlation method, which requires reference signals to determine borders, influence speed of sound (SOS) values for articular cartilage. Left femoral condyle samples from a 6-month-old pig and a 3 year-old pig were used. Radiofrequency signals from the cartilage surface and cartilage-bone interface were acquired using the ultrasound transducer for nine points in each sample. TOF was calculated by three amplitude-related methods (peak amplitude, peak envelope, signal phase) and a cross-correlation method. Cartilage thickness was measured microscopically, and SOS was calculated at each point. Mean (+/- standard deviation) SOSs in cartilage from the 9-point measurement by the four TOF methods were 1488 +/- 51, 1488 +/- 48, 1487 +/- 54, and 1466 +/- 51 m/s (for peak amplitude, peak envelope, signal phase, and cross correlation methods, respectively) for the 6-month-old pig, and 1709 +/- 107, 1717 +/- 104, 1713 +/- 105, and 1695 +/- 138 m/s, respectively, for the 3-year old pig. Paired t testing identified no significant differences between the amplitude-related methods and the cross-correlation method, although SOS values yielded by the amplitude-related methods tended to be higher than those from the cross-correlation method. These results suggest that amplitude-related methods of TOF measurement and the cross-correlation method are equivalently applicable to articular cartilage SOS measurement when a wave is clearly reflected from cartilage. TOF methods should thus be considered in studies on SOS measurement. PMID- 27278591 TI - Contrast-enhanced ultrasonographic image of gangrenous gallbladder. PMID- 27278593 TI - Editor's Note. PMID- 27278592 TI - Another "double bubble" sign or "double bladder" sign: fetal intra-abdominal umbilical vein varix. AB - Fetal intra-abdominal umbilical vein varix increases the incidence of fetal/neonatal morbidity and mortality. Its early diagnosis may be clinically important. For a case of this disorder, we have proposed the new name of "double bladder" sign; "another double bubble" sign may also illustrate this disorder. PMID- 27278594 TI - Correction: From FOX-7 to H-FOX to insensitive energetic materials with hypergolic properties. AB - Correction for 'From FOX-7 to H-FOX to insensitive energetic materials with hypergolic properties' by Dharavath Srinivas et al., Chem. Commun., 2016, 52, 7668-7671. PMID- 27278596 TI - Richard Fieldhouse: Sessional GP supporter. PMID- 27278606 TI - The expression of miR-21 and miR-143 is deregulated by the HPV16 E7 oncoprotein and 17beta-estradiol. AB - MicroRNAs (miRNAs) are a class of non-coding RNAs that negatively regulate their target mRNAs at a posttranscriptional level, thereby affecting crucial processes in cancer development. However, little is known about the molecular events that control expression of miRNAs in cervical cancer (CC). HPV16 E7 oncoprotein in conjunction with estrogen are sufficient to produce high grade cervical dysplasia and invasive cervical malignancies in a mouse model. In the present study, we determined the potential role that the E7 oncoprotein and 17beta-estradiol (E2) play in the deregulation of miR-21 and miR-143 expression levels by these two risk factors. We found that, while the expression of miR-21 was upregulated and the expression of miR-143 was downregulated by the HPV16 E7 oncoprotein in vivo, and in vitro and that E2 treatment is also implicated in the deregulation of these important miRNAs in vivo. Sustained upregulation of miR-21 resulted in suppression of PTEN expression, and repression of miR-143 increased the mRNA and protein levels from Bcl-2. These results suggested that HPV type 16 E7 oncoprotein and E2 play an important role in regulating miR-21 and miR-143 expression. We have observed similar results in CC patients containing HPV16 sequences, suggesting that these miRNAs could serve as diagnostic biomarkers in CC. The present study highlights the roles of miRNAs in cervical tissue and implicates these important molecules in cervical carcinogenesis. PMID- 27278607 TI - First report on spinal metastasis in childhood-onset craniopharyngioma. PMID- 27278595 TI - The legacy of the F344 rat as a cancer bioassay model (a retrospective summary of three common F344 rat neoplasms). AB - The Fischer 344 (F344) rat was used by the National Toxicology Program (NTP) for over 5 decades for toxicity and carcinogenicity studies. However, in 2006, the NTP decided to switch to a different rat stock due largely to high background control incidences of Leydig cell tumors (LCTs) and mononuclear cell leukemia (MNCL), also known as large granular lymphocytic (LGL) leukemia. In the current review, we aim (1) to provide a summary of NTP bioassays with treatment associated effects involving MNCL and LCTs in addition to male F344-specific tunica vaginalis mesothelioma (TVM); (2) to describe important pathobiological differences between these F344 rat tumor responses and similar target tissue tumor response in humans; and (3) to present the NTP reasons for switching away from the F344 rat. We show that due to the highly variable background incidence of F344 MNCL, more reliance on historical control data than is usual for most tumor responses is warranted to evaluate potential effect of any chemical treatment in this rat strain. The high spontaneous incidence of LCTs in the testes of male F344 rats has made this tumor endpoint of little practical use in identifying potential testicular carcinogenic responses. TVM responses in F344 rats have a biological plausible relationship to LCTs unlike TVM in humans. Given their high spontaneous background incidence and species-specific biology, we contend that MNCL and LCT, along with TVM responses, in F344 rat carcinogenicity studies are inappropriate tumor types for human health risk assessment and lack relevance in predicting human carcinogenicity. PMID- 27278608 TI - Comment on: Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients? PMID- 27278610 TI - Journal of Echocardiography Award for the Year 2012. PMID- 27278609 TI - Beyond in-phase and anti-phase coordination in a model of joint action. AB - In 1985, Haken, Kelso and Bunz proposed a system of coupled nonlinear oscillators as a model of rhythmic movement patterns in human bimanual coordination. Since then, the Haken-Kelso-Bunz (HKB) model has become a modelling paradigm applied extensively in all areas of movement science, including interpersonal motor coordination. However, all previous studies have followed a line of analysis based on slowly varying amplitudes and rotating wave approximations. These approximations lead to a reduced system, consisting of a single differential equation representing the evolution of the relative phase of the two coupled oscillators: the HKB model of the relative phase. Here we take a different approach and systematically investigate the behaviour of the HKB model in the full four-dimensional state space and for general coupling strengths. We perform detailed numerical bifurcation analyses and reveal that the HKB model supports previously unreported dynamical regimes as well as bistability between a variety of coordination patterns. Furthermore, we identify the stability boundaries of distinct coordination regimes in the model and discuss the applicability of our findings to interpersonal coordination and other joint action tasks. PMID- 27278611 TI - Discrimination between fibroelastic deficiency and Barlow disease using parameters of mitral annulus derived from real-time three-dimensional echocardiography. AB - BACKGROUND: Discrimination between fibroelastic deficiency (FED) and Barlow disease (BD) is crucial for decision making in mitral valve surgery as BD is a more complex lesion demanding high surgical skill and experience. In our study we focused on the differentiation of FED from BD using three-dimensional (3D) echocardiographic parameters of the mitral annulus assessed by the mitral valve quantification (MVQ) program. METHODS: We examined 90 patients (30 women) with FED and BD aged 37-76 years. The following parameters of the mitral annulus were assessed using the MVQ program: bicommissural and anteroposterior diameter of the mitral annulus, 3D annulus circumference, minimal surface spanning the annulus, and mitral annulus height. The study group was subdivided into 2 subgroups according to the intraoperative findings: the first subgroup comprised 60 individuals (19 women) with FED and the second subgroup comprised 30 patients (11 women) with BD. The discrimination between patients with BD and FED was carried out by univariate as well as multivariate statistical methods. RESULTS: BD and FED patients differed highly significantly in all parameters of the mitral annulus (t test), values of all parameters in BD being higher. In the classification tree modeling, the diagnoses were completely separated by a single parameter-mitral annulus height-with a cutoff value of 6.55 mm. This value and higher stands for BD. Multivariate analysis treating all the variables showed similar results, so the use of a single indicator variable is preferable. CONCLUSION: The only parameter-mitral annulus height-can be used for discrimination between Barlow disease and fibroelastic deficiency. PMID- 27278612 TI - Usefulness of right ventricular tissue Doppler imaging for diagnosis of right ventricular myocardial infarction. AB - BACKGROUND: Right ventricular myocardial infarction (RVMI) is a complication of acute inferior myocardial infarction and sometimes causes severe hemodynamic disturbance. It is therefore important to promptly detect RVMI and assess the severity of right ventricular (RV) dysfunction. Tissue Doppler imaging (TDI) is a useful method to assess left ventricular function and RV function. In this study, we investigated the possibility of diagnosing RVMI using tricuspid annular velocity determined by TDI. METHODS: Thirty consecutive patients with first acute inferior myocardial infarction were studied. The diagnosis of RVMI was based on an ST-segment elevation of at least 0.1 mV in lead V4R. The patients were classified into 12 patients with RVMI (the RVMI group) and 18 patients without RVMI (non-RVMI group). All patients underwent two-dimensional echocardiography, pulsed Doppler and TDI, and coronary angiography within 48 h after onset of myocardial infarction. Tricuspid inflow velocity was recorded by pulsed Doppler and early diastolic tricuspid inflow velocity (TVE) was measured. Peak early diastolic velocity of the tricuspid annulus (TVe') at the RV free wall was recorded using TDI. The ratio of TVE to TVe' (TVE/TVe') was calculated. RESULTS: TVe' was significantly lower in the RVMI group compared to that in the non-RVMI group (5.9 +/- 1.3 vs. 9.1 +/- 3.1; p = 0.0025). On the basis of a TVe' cutoff value of less than 8.3 cm/s, RVMI was diagnosed with 100 % sensitivity and 61 % specificity. CONCLUSIONS: The early diastolic tricuspid annular velocity determined by TDI is a noninvasive and sensitive index for diagnosing RVMI. PMID- 27278613 TI - Prosthetic tricuspid valve dysfunction assessed by three-dimensional transthoracic and transesophageal echocardiography. AB - A 39-year-old male who had undergone tricuspid valve replacement for severe tricuspid regurgitation was admitted with palpitation and general edema. Two dimensional (2D) echocardiography showed tricuspid prosthetic valve dysfunction. Additional three-dimensional (3D) transthoracic and transesophageal echocardiography (TEE) could clearly demonstrate the disabilities of the mechanical tricuspid valve. Particularly, 3D TEE demonstrated a mass located on the right ventricular side of the tricuspid prosthesis, which may have caused the stuck disk. This observation was confirmed by intra-operative findings. PMID- 27278615 TI - Heart failure induced by the restrictive left ventricle due to hiatus hernia. AB - A 76-year-old woman presented with shortness of breath and dyspnea after the intake of meals. Chest X-ray showed pulmonary congestion and pleural effusion. Computed tomography disclosed a hiatus hernia. Echocardiography demonstrated that the motion of the posterior wall in the left ventricle (LV) was paradoxically by the hiatus hernia, although LV ejection fraction was preserved. The restriction of LV by hiatus hernia could cause heart failure and open surgical repair of the hiatus hernia was performed. Dyspnea after the intake of meals disappeared and no recurrence of heart failure was observed in the subsequent period of several years. PMID- 27278614 TI - Isolated accessory mitral valve tissue in an asymptomatic elderly patient. AB - Accessory mitral valve tissue is a membranous or tumor-like structure observed in the left ventricular outflow tract. This congenital anomaly has been reported in more than 100 cases since 1842; however, most of them were found in patients with complex cardiac malformations. We report a 72-year-old Asian woman with isolated accessory mitral valve tissue incidentally found during the evaluation of hypertension and arrhythmia. Her left ventricular outflow tract obstruction was mild. Because worsening of the left ventricular outflow tract obstruction was reported in patients without significant obstruction at the time of diagnosis, periodical echocardiographic follow-up is necessary. PMID- 27278616 TI - A case of left ventricular aneurysm caused by localized myocardial infarction. AB - A 73-year-old man was hospitalized for unstable angina pectoris with no history of myocardial infarction. After undergoing percutaneous coronary intervention, left ventriculography incidentally revealed a cavity in the anterior wall, and echocardiography found the cavity wall to be dyskinetic. Myocardial contrast echocardiography revealed that the wall of the cavity was surrounded by myocardial tissue with low perfusion. Furthermore, radial strain in the wall of the cavity was low. Myocardial scintigraphy showed a localized defect on the anterior wall. The patient was finally diagnosed as true aneurysm after asymptomatic and localized myocardial infarction, and has since been followed up by echocardiography in the outpatient clinic. PMID- 27278617 TI - An echogenic mass on the aortic valve. PMID- 27278618 TI - Giant pulmonary artery aneurysm due to pulmonary stenosis. PMID- 27278619 TI - Post myocardial infarction ventricular septal defect causing left ventricular intramyocardial dissecting hematoma: a very rare complication. PMID- 27278621 TI - Aortic redissection after glue repair: a rare echocardiographic finding. PMID- 27278620 TI - Patent foramen ovale with a riding vermicular thrombus arising from a pacemaker lead. PMID- 27278622 TI - A giant right atrial mass: intracavitary extension from hepatocellular carcinoma. PMID- 27278623 TI - Increased heart murmur with standing in a case of pectus excavatum. PMID- 27278625 TI - Transport of fatty acids within plasma lipoproteins in lactating and non lactating cows fed on fish oil and hydrogenated palm oil. AB - The aim of this study was to elucidate the effect of dietary fish oil (FO) and a blend of FO and hydrogenated palm oil (FOPO) on transport of fatty acids (FA) within plasma lipoproteins in lactating and non-lactating cows. Two trials were conducted (one with lactating and another with non-lactating dairy cows) in two 3 * 3 Latin squares that included three periods of 21 days. Dietary treatments for lactating cows consisted of a basal diet (Control; no fat supplement), and fat supplemented diets containing FO (500 g/day/cow) and FOPO (250 FO + 250 g/day/cow hydrogenated palm oil). For non-lactating cows, dietary treatments consisted of a basal diet (Control; no fat supplement), and fat-supplemented diets containing FO (170 g/day/cow) and FOPO (85 FO + 85 hydrogenated palm oil g/day/cow). In lactating cows, compared with control and FOPO, FO increased C16:0, C18:3 cis-9, 12, 15, C18:2 cis-9, trans-11 and total saturated and polyunsaturated FA in plasma and increased C16:0, C18:2 cis-9, trans-11, total polyunsaturated and total polyunsaturated n-6 in high-density lipoprotein (HDL), whereas in non lactating cows, compared with control and FOPO, FO increased C16:0, C18:1 trans 11, C18:2 trans-9, 12, C18:2 cis-9, trans-11, C20:5 n-3 and total saturated and polyunsaturated FA in plasma; C16:0, C18:1 trans-11, C18:1 cis-9, C18:2 trans-9, 12, C20:5 n-3 and total monounsaturated FA in HDL; and C18:1 trans-6-8, C18:1 trans-9, C18:1 trans-10, C18:1 trans-11, C18:3 cis-9, 12, 15 and C20:5 n-3 in low density lipoprotein (LDL). FO increased C20:5 n-3 in plasma and lipoproteins in non-lactating cows and increased C18:3 cis-9, 12, 15 in plasma (in lactating cows) and LDL (in non-lactating cows). We concluded from results of this study that in bovine plasma, the LDL fraction appears to be the main lipoprotein transporting C18:1 trans isomers and is more responsive than other lipoprotein fractions to variation in supply of dietary lipids. PMID- 27278624 TI - Macrophages transfer antigens to dendritic cells by releasing exosomes containing dead-cell-associated antigens partially through a ceramide-dependent pathway to enhance CD4(+) T-cell responses. AB - Defects in rapid clearance of apoptotic cells lead to an accumulation of dead cells (late apoptotic or secondary necrotic cells), which results in an aberrant immune response. However, little is known about whether and how macrophages (Mphis) cooperate with dendritic cells (DCs) in the presentation of dead-cell associated antigens in this process. By transferring high numbers of dead cells to mimic a failure of apoptotic cell clearance in vivo, we found that Mphis and neutrophils were the predominant phagocytes in the uptake of dead cells in the spleen. Moreover, both Mphis and DCs were required for an optimal CD4(+) T-cell response triggered by dead-cell-associated antigens. Importantly, although Mphis alone had a poor capacity for antigen presentation, they could transfer phagocytosed antigens to DCs for potent antigen presentation to enhance T-cell responses. Finally, we found that exosomes released from Mphis acted as a transmitter to convey antigens to DCs partially in a ceramide-dependent manner, since treatment with the neutral sphingomyelinase inhibitor GW4869 and spiroepoxide resulted in a significant reduction of T-cell proliferation in vitro and in vivo. These findings point to a novel pathway of cross-talk between Mphis and DCs, which will be helpful to explain possible mechanisms for autoimmune diseases characterized by increased rates of apoptosis. PMID- 27278627 TI - Male-specific colon motility dysfunction in the TashT mouse line. AB - BACKGROUND: In Hirschsprung disease (HSCR), the absence of myenteric neural ganglia in the distal bowel prevents motility and thereby causes functional intestinal obstruction. Although surgical resection of the aganglionic segment allows HSCR children to survive this condition, a number of patients still suffer from impaired motility despite having myenteric ganglia in their postoperative distal bowel. Such phenomenon is also observed in patients suffering from other enteric neuropathies and, in both cases, colonic dysmotility is believed to result from abnormalities of myenteric ganglia and/or associated interstitial cells of Cajal (ICC). To better understand this, we used a recently described HSCR mouse model called TashT. METHODS: Intestinal motility parameters were assessed and correlated with extent of aganglionosis and with neuronal density in ganglionated regions. The neural composition of the myenteric plexus and the status of ICC networks was also evaluated using immunofluorescence. KEY RESULTS: TashT(Tg/Tg) mice display a strong male bias in the severity of both colonic aganglionosis and hypoganglionosis, which are associated with male-specific reduced colonic motility. TashT(Tg/Tg) male mice also exhibit a specific increase in nNos(+) neurons that is restricted to the most distal ganglionated regions. In contrast, Calretinin(+) myenteric neurons, Sox10(+) myenteric glial cells, and cKit(+) ICC are not affected in TashT(Tg/Tg) mice. CONCLUSIONS AND INFERENCES: Male-specific impairment of colonic motility in TashT(Tg/Tg) mice is associated with both severe hypoganglionosis and myenteric neuronal imbalance. Considering these parameters in the clinic might be important for the management of postoperative HSCR patients. PMID- 27278626 TI - Small RNA transcriptomes of mangroves evolve adaptively in extreme environments. AB - MicroRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs) are key players in plant stress responses. Here, we present the sRNA transcriptomes of mangroves Bruguiera gymnorrhiza and Kandelia candel. Comparative computational analyses and target predictions revealed that mangroves exhibit distinct sRNA regulatory networks that differ from those of glycophytes. A total of 32 known and three novel miRNA families were identified. Conserved and mangrove-specific miRNA targets were predicted; the latter were widely involved in stress responses. The known miRNAs showed differential expression between the mangroves and glycophytes, reminiscent of the adaptive stress-responsive changes in Arabidopsis. B. gymnorrhiza possessed highly abundant but less conserved TAS3 trans-acting siRNAs (tasiRNAs) in addition to tasiR-ARFs, with expanded potential targets. Our results indicate that the evolutionary alteration of sRNA expression levels and the rewiring of sRNA-regulatory networks are important mechanisms underlying stress adaptation. We also identified sRNAs that are involved in salt and/or drought tolerance and nutrient homeostasis as possible contributors to mangrove success in stressful environments. PMID- 27278628 TI - Genetic divergence of enterovirus D68 in China and the United States. AB - The largest outbreak of human enterovirus 68 (EV-D68) infections associated with severe respiratory illness and neurological complications emerged from the United States in 2014. China reported the circulation of EV-D68 since 2006, but these cases were sporadic and did not display neurological symptoms. Yet viral determinants responsible for the difference in prevalence between China and the U.S. were not clear. We analyzed the genome of 64 reported Chinese EV-D68 strains and found that genogroup replacement has occurred in China since 2006. The six coding mutations (M291T, V341A, T860N, D927N, S1108G and R2005K) associated with neurovirulence reported in American strains were not found in Chinese strains. Moreover, 2014 Chinese strains had a unique R220A mutation in the puff region of VP2 while R220E mutation occurred in other strains. Like other enteroviruses, the loop sequences of the domain X and Y in the 3'-UTR of the Chinese strains are complementary. However, the X loop sequences of the 2014 American strains were not complementary but identical to Y loop sequences. These results indicate that different EV-D68 strains circulated in China and America and the mutations might be responsible for different prevalence. Our findings also provide new evidence for the sequence diversity of EV-D68. PMID- 27278629 TI - Surgical anatomy of the right hepatic artery in Rouviere's sulcus evaluated by preoperative multidetector-row CT images. AB - BACKGROUND: Lymph node dissection in Rouviere's sulcus (RS) is essential during left-sided hepatectomy and caudate lobectomy for hilar cholangiocarcinoma. However, the small segmental or subsegmental arteries (SA/SSA) are often encountered in RS and must be preserved to prevent critical complications, such as liver infarction or liver failure. The aim of this study is to elucidate the anatomy of SA/SSA around RS, which should be understood preoperatively. METHODS: Between January 2008 and April 2013 from a total of 124 consecutive patients with hilar cholangiocarcinoma, preoperative multidetector-row computed tomography (MDCT) images were obtained at our institution and evaluated. The bifurcation patterns of the SA/SSA, the courses of the posterior SA/SSA and the bifurcation site of the SA/SSA were investigated using MDCT images. RESULTS: The typical form, in which right hepatic artery (RHA) bifurcated into the anterior (Aant) and posterior (Apost) hepatic artery and thereafter, Aant/Apost bifurcated into the SA and SSA, was observed in 75 patients (60.5 %). On the other hand, the atypical forms, in which the SA/SSA were independently branched off from RHA before the main bifurcation of the Aant and Apost, were observed in 43 patients (34.7 %). The prior branched arteries supplied the whole or ventral area of segment VI (A6 or A6a) in 11 patients (8.9 %), which was most commonly observed in the atypical form. 15 patients (34.9 %) of the 43 patients with atypical form had partially supraportal posterior branches, that showed early-bifurcated posterior SA/SAA following supraportal course, while the other posterior SA/SSA followed infraportal course. The SA/SSA were extrahepatically bifurcated in 82 patients (66.1 %), comprised of all 43 atypical form and 39 of typical form, while the SA/SSA were intrahepatically bifurcated in remaining 36 patients of typical forms (29.0 %). CONCLUSION: The extrahepatic bifurcation of the SA/SSA from RHA was relatively common. The early-bifurcated SA/SSA was often observed (34.7 % of total cohort) and, in 34.8 % of those atypical forms, posterior SA/SSA from RHA followed a supraportal course. The detailed preoperative knowledge of the anatomy, including SA/SSA, is crucial for left-sided hepatectomy for hilar cholangiocarcinoma. PMID- 27278630 TI - Screening for Congenital Heart Disease in Infants with Down Syndrome: Is Universal Echocardiography Necessary? AB - Current guidelines recommend that all neonates with Down syndrome (DS) be screened for congenital heart disease (CHD) with an echocardiogram. We sought to determine the effectiveness of a more accessible and less expensive screening strategy consisting of physical examination, electrocardiogram (ECG), and chest X ray. The Intermountain Healthcare Enterprise Data Warehouse was used to identify infants with a positive karyotype for DS who were born between January 1, 2000, and June 30, 2012. Infants with the results of an echocardiogram, physical examination, ECG, and chest X-ray documented at age <=6 months were included. Infants with an abnormality on physical examination, ECG, or chest X-ray were considered to have a positive screen. Echocardiography was the gold standard for calculating sensitivity, specificity, positive and negative predictive values for major CHD, defined as any heart defect that would typically require intervention during early childhood. Of 408 eligible infants, 240 (59 %) had major CHD, of whom 228 (95 %) had a positive screen. Screening missed eight infants with moderate/large patent ductus arteriosus and four infants with a moderate/large atrial septal defect. In 11 of these infants, the defect resolved spontaneously by age <=4 months. One infant had a moderate atrial septal defect persisting at 2 year follow-up. Sensitivity and specificity of the screening for detecting CHD were 95 % (CI 92-98 %) and 41 % (CI 32-47 %); positive and negative predictive values were 69 % (CI 63-73 %) and 85 % (CI 75-92 %). Screening with physical examination, ECG, and chest X-ray is an effective method of identifying which infants with DS should have an echocardiogram. This method would have resulted in 69 (17 %) fewer echocardiograms without missing infants with major CHD. PMID- 27278631 TI - Initial Experience with the Nit-Occlud ASD-R: Short-Term Results. AB - We aim to assess the safety, feasibility and efficacy of the new Nit-Occlud ASD-R (NOASD-R) device. From 2014 to 2015, transcatheter closure of atrial septal defect (ASD) using the NOASD-R was performed in 30 consecutive patients. The standard deployment technique as the left upper pulmonary vein approach was used in 25 patients. Right upper pulmonary vein approach was required in five. The median age was 6 years (range 3.5-60 years), and median weight was 21.5 kg (14-79 kg). Implantation was successful in all patients. The median size of devices was 16 mm (12.0-26.0 mm). The mean device size/2D defect diameter ratio was 1.26 +/- 0.09 (1.12-1.40). The mean device size/color flow diameter ratio was 1.07 +/- 0.06 (range 1.0-1.22). Releasing problem was encountered in three patients. A device-related erosion on the day after the closure was observed in one patient. No further device-related complication (erosion, embolization or dislodgement of the device) was encountered in a median follow-up period of 10 months (range 2-14 months). Complete occlusion has occurred in all at follow-up. NOASD-R is a feasible and effective device for use in the transcatheter occlusion of moderate to large secundum ASDs in selected patients. The occurrence of the erosion on the right atrial roof may be due to the high localization of the device and the larger size of the right disk. PMID- 27278632 TI - Diagnostic Utility of Three-Dimensional Rotational Angiography in Congenital Cardiac Catheterization. AB - We evaluated the diagnostic utility of the three modalities of three-dimensional rotational angiography (3DRA): rotational angiography (RA), multiplanar reformat (MPR) and three-dimensional angiographic reconstruction (3D-R) in pediatric cardiac catheterization. The 3DRA studies were classified by anatomy of interest based on our injection protocol: pulmonary arteries (PA), aorta, cavopulmonary connection (CPC), and others. Retrospective review of 3DRA images by two reviewers for each modality was conducted with grading as inferior, similar, or superior in comparison with the diagnostic quality of fixed-plane angiography (FPA). The percentages of grades for each modality were averaged. Weighted kappa statistic was used to evaluate inter-rater reliability. In total, 114 3DRA studies were performed on 87 patients between August 2010 and March 2012. Median age was 2.7 years (1 day-48.4 years) and median weight 12.1 kg (3.6-106.5 kg). For RA: 79.4 % of the studies were of diagnostic quality and 52.2 % were superior; 3D-R: 82 % were of diagnostic quality and 65.8 % were superior; and MPR: 83.5 % were of diagnostic quality and 63 % were superior. Overall 3DRA technologies (RA, 3D-R, MPR) were of diagnostic quality or better in 111/114 (97.4 %) studies and 103/114 (90.4 %) were judged superior. Most common reasons for inferior grading were limited opacification and metallic artifact. In pediatric cardiac catheterization, 3DRA imaging was of diagnostic quality and frequently provided additional clinically relevant data when compared to FPA. PMID- 27278633 TI - Early Postoperative Albumin Administration Contributes to Morbidity After the Fontan Operation. AB - The Fontan operation has low mortality, but is associated with significant postoperative morbidity, including prolonged chest tube output (PCTO), which is associated with prolonged hospital length of stay (PLOS). We sought to identify variables present early in the clinical course that could predict patients at high risk for PCTO and PLOS. Retrospective data were collected on 84 Fontan (extracardiac conduit) operations from 1/2008 to 12/2013 at a single institution. PCTO was defined as >=8 days (>75th percentile); PLOS was defined as >=12 days postoperatively (>75th percentile). Multivariate regression was used to determine covariates associated with PCTO and PLOS. Median age was 3.5 years (IQR 3-5); weight was 14.5 kg (IQR 13-17). There was no mortality. LOS was 9 days (IQR 3 11), and duration of chest tube drainage 6 days (IQR 5-8) at 15 ml/kg/day (IQR 9 20). In univariate analysis, only systemic right ventricle, 24-h 5 % albumin administration, 24-h fluid balance, and 12-h inotrope score were associated with PCTO. In multivariate analysis, only 5 % albumin administration in first 24 h (p < 0.001) and PCTO were independently associated with PLOS. ROC curve analysis showed patients receiving >25 ml/kg of 5 % albumin in first 24-h predicted PLOS (94 % specificity, 93 % sensitivity, AUC = 0.95, p < 0.001). Increased colloid in the first 24-h post-CPB strongly predicts PCTO and PLOS after Fontan operation, potentially providing an early identification of a cohort with unfavorable Fontan physiology. A better understanding of the role of colloid resuscitation after Fontan is necessary, and efforts to reduce perioperative colloid administration could decrease hospital morbidity. PMID- 27278634 TI - Consumers' Patient Portal Preferences and Health Literacy: A Survey Using Crowdsourcing. AB - BACKGROUND: eHealth apps have the potential to meet the information needs of patient populations and improve health literacy rates. However, little work has been done to document perceived usability of portals and health literacy of specific topics. OBJECTIVE: Our aim was to establish a baseline of lung cancer health literacy and perceived portal usability. METHODS: A survey based on previously validated instruments was used to assess a baseline of patient portal usability and health literacy within the domain of lung cancer. The survey was distributed via Amazon's Mechanical Turk to 500 participants. RESULTS: Our results show differences in preferences and literacy by demographic cohorts, with a trend of chronically ill patients having a more positive reception of patient portals and a higher health literacy rate of lung cancer knowledge (P<.05). CONCLUSIONS: This article provides a baseline of usability needs and health literacy that suggests that chronically ill patients have a greater preference for patient portals and higher level of health literacy within the domain of lung cancer. PMID- 27278635 TI - Second denervation in a patient with resistant hypertension. PMID- 27278637 TI - Differential Toxicities of Nickel Salts to the Nematode Caenorhabditis elegans. AB - This study focused on assessing whether nickel (Ni) toxicity to the nematode Caenorhabditis elegans was affected by the molecular structure of the Ni salt used. Nematodes were exposed to seven Ni salts [Ni sulfate hexahydrate (NiSO4.6H2O), Ni chloride hexahydrate (NiCl2.6H2O), Ni acetate tetrahydrate (Ni(OCOCH3)2.4H2O), Ni nitrate hexahydrate (N2NiO6.6H2O), anhydrous Ni iodide (NiI2), Ni sulfamate hydrate (Ni(SO3NH2)2.H2O), and Ni fluoride tetrahydrate (NiF2.4H2O)] in an aquatic medium for 24 h, and lethality curves were generated and analyzed. Ni fluoride, Ni iodide, and Ni chloride were most toxic to C. elegans, followed by Ni nitrate, Ni sulfamate, Ni acetate, and Ni sulfate. The LC50 values of the halogen-containing salts were statistically different from the corresponding value of the least toxic salt, Ni sulfate. This finding is consistent with the expected high bioavailability of free Ni ions in halide solutions. We recommend that the halide salts be used in future Ni testing involving aquatic invertebrates. PMID- 27278636 TI - Chronic ischemic mitral regurgitation and papillary muscle infarction detected by late gadolinium-enhanced cardiac magnetic resonance imaging in patients with ST segment elevation myocardial infarction. AB - BACKGROUND: Both papillary muscle infarction (PMI) and chronic ischemic mitral regurgitation (CIMR) are associated with reduced survival after myocardial infarction. The influence of PMI on CIMR and factors influencing both entities are incompletely understood. OBJECTIVES: We sought to determine the influence of PMI on CIMR after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and to define independent predictors of PMI and CIMR. METHODS: Between January 2011 and May 2013, 263 patients (mean age 57.8 +/- 11.5 years) underwent late gadolinium-enhanced cardiac magnetic resonance imaging and transthoracic echocardiography 4 months after PCI for STEMI. Infarct size, PMI, and mitral valve and left ventricular geometric and functional parameters were assessed. Univariate and multivariate analyses were performed to identify predictors of PMI and CIMR (>=grade 2+). RESULTS: PMI was present in 61 patients (23 %) and CIMR was present in 86 patients (33 %). In patients with PMI, 52 % had CIMR, and in patients without PMI, 27 % had CIMR (P < 0.001). In multivariate analyses, infarct size [odds ratio (OR) 1.09 (95 % confidence interval 1.04-1.13), P < 0.001], inferior MI [OR 4.64 (1.04-20.62), P = 0.044], and circumflex infarct-related artery [OR 8.21 (3.80-17.74), P < 0.001] were independent predictors of PMI. Age [OR 1.08 (1.04-1.11), P < 0.001], infarct size [OR 1.09 (1.03-1.16), P = 0.003], tethering height [OR 19.30 (3.28-113.61), P = 0.001], and interpapillary muscle distance [OR 3.32 (1.31-8.42), P = 0.011] were independent predictors of CIMR. CONCLUSIONS: The risk of PMI is mainly associated with inferior infarction and infarction in the circumflex coronary artery. Although the prevalence of CIMR is almost doubled in the presence of PMI, PMI is not an independent predictor of CIMR. Tethering height and interpapillary muscle distance are the strongest independent predictors of CIMR. PMID- 27278639 TI - I see what you are saying. AB - The motor cortex in the brain tracks lip movements to help with speech perception. PMID- 27278638 TI - PRDM8 internal promoter hyperhydroxymethylation correlates with increased expression of the corresponding transcript in Down syndrome. AB - Down syndrome (DS) is the most common form of intellectual disability associated with central nervous system abnormalities and results from an extra complete or partial copy of human chromosome 21. However, whether DNA hydroxymethylation is perturbed in a specific gene associated with DS phenotypes, or the alteration of DNA hydroxymethy-lation results in changes of gene expression in DS remains unidentified. The current study mapped 5-methylcytosine and 5 hydroxymethylcytosine at CpG islands of the PR domain containing 8 (PRDM8) in the peripheral blood of 16 DS and 19 normal samples by oxidative bisulfite pyrosequencing. Furthermore, the association of the expression levels of the two transcripts and epigenetic modification in different genomic contexts of PRDM8 was analyzed. The results demonstrated hypermethylation and hyperhydroxymethylation at the internal promoter of PRDM8 in DS, and significantly increased the expression of PRDM8 transcript variant 2 in the DS patients (median 3.9 vs. 2.04; P=0.016), accompanied by a positive correlation between the expression of two PRDM8 transcripts and hydroxymethylation at the corresponding external and internal promoters in patients, although not in the controls. A similar association was observed between the expression of transcript variant 1 and intragenic methylation of PRDM8. Taken together, the results of the present study suggest a critical role for DNA hydroxymethylation and methylation in regulating abnormal PRDM8 overexpression in DS. PMID- 27278640 TI - Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. AB - Psychoactive cannabinoids from the marijuana plant (phytocannabinoids), from the body (endocannabinoids), and from the research lab (synthetic cannabinoids) produce their discriminative stimulus effects by stimulation of CB1 receptors in the brain. Early discrimination work with phytocannabinoids confirmed that Delta9 tetrahydrocannabinol (Delta9-THC) is the primary psychoactive constituent of the marijuana plant, with more recent work focusing on characterization of the contribution of the major endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), to Delta9-THC-like internal states. Collectively, these latter studies suggest that endogenous increases in both anandamide and 2-AG seem to be optimal for mimicking Delta9-THC's discriminative stimulus effects, although suprathreshold concentrations of anandamide also appear to be Delta9-THC-like in discrimination assays. Recently, increased abuse of synthetic cannabinoids (e.g., "fake marijuana") has spurred discrimination studies to inform regulatory authorities by predicting which of the many synthetic compounds on the illicit market are most likely to share Delta9-THC's abuse liability. In the absence of a reliable model of cannabinoid self-administration (specifically, Delta9-THC self administration), cannabinoid discrimination represents the most validated and pharmacologically selective animal model of an abuse-related property of cannabinoids - i.e., marijuana's subjective effects. The influx of recent papers in which cannabinoid discrimination is highlighted attests to its continued relevance as a valuable method for scientific study of cannabinoid use and abuse. PMID- 27278641 TI - Mechanisms of Inflammation-Associated Depression: Immune Influences on Tryptophan and Phenylalanine Metabolisms. AB - Metabolic parameters have a direct role in the regulation of immune cell function. Thereby the inflammation-induced metabolism of aromatic amino acids, most importantly of tryptophan and phenylalanine, plays a central role. In addition, neuropsychiatric conditions that go along with disorders that are characterized by acute or chronic inflammation, such as the development of depression, decreased quality of life or cognitive impairments, are connected to disturbed amino acid and subsequent neurotransmitter metabolism.The bioanalytical procedures for the determination of concentrations of tryptophan and phenylalanine and their respective first stable intermediates kynurenine and tyrosine as well as some analytical finesses and potential sources of errors are discussed in this chapter. Monitoring of these immunometabolic parameters throughout therapies in addition to biomarkers of immune response and inflammation such as neopterin can be useful to determine disease progression but also to plan psychiatric interventions timely, thus to establish personalized treatments. PMID- 27278642 TI - The Promise and Limitations of Anti-Inflammatory Agents for the Treatment of Major Depressive Disorder. AB - This review provides a critical perspective on recent meta-analyses suggesting that several anti-inflammatory modalities, including nonsteroidal anti inflammatory drugs (NSAIDs), omega-3 fatty acids, and cytokine antagonist, possess generalizable antidepressant properties. By examining confounds and limitations in the available literature it is suggested that current data suggest that only a sub-group of individuals with major depressive disorder (MDD) have evidence of increased inflammatory biomarkers and it is in these individuals that anti-inflammatory agents show promise for reducing depressive symptoms. The treatment implications of this cautionary perspective are discussed. PMID- 27278643 TI - Author response: The essense of primum no nocere--striking a balance between benefit and harm. PMID- 27278644 TI - The use of a three-dimensional endoscope for different skull base tumors: results of a preliminary extended endonasal surgical series. AB - BACKGROUND: The evolution of skull base surgery over the past decade has been influenced by advancement in visualization technology. Recently, as a result of such improvements, three-dimensional (3-D) scopes have been widely used during endoscopic endonasal approaches. In the present study, we describe the use of 3-D stereoscopic endoscope for the treatment of a variety of skull base lesions. METHODS: From January 2010 to June 2015, a 3-D endoscopic endonasal approach (4 and 4.9 mm, 0 degrees , and 30 degrees rigid endoscopes) was performed in 70 patients with the following lesions: 42 large extrasellar pituitary macroadenomas, seven tuberculum sellae meningiomas, seven clivus chordomas, five craniopharyngiomas, three fibrous dysplasia of the clivus, three sinonasal malignancies, one orbital lymphangioma, one trigeminal neurinoma, one primary suprasellar lymphoma. RESULTS: Total tumor removal was obtained in 50 patients (71.4 %) while in 14 (20 %), subtotal removal was possible in six (8.6 %) only partial removal was achieved. Overall complications included diabetes insipidus in eight patients (11.4 %), hypopituitarism in seven patients (10 %), CSF leak in five patients (7.1 %), cranial nerve injury in two patients (2.8 %), panhypopituitarism in two patients (2.8 %), meningitis in one (1.4 %) and one postoperative central retinal artery occlusion (1.4 %). There was no mortality in the series. The mean follow-up time was 39 months (range, 6-72 months). CONCLUSIONS: In our experience, the 3-D endoscope represents a critical development in visualization, thus enabling improved hand-eye coordination and depth perception, which are mandatory for the management of complex intradural neurovascular structures during tumor removal surgery. PMID- 27278645 TI - Evidence for cohesin sliding along budding yeast chromosomes. AB - The ring-shaped cohesin complex is thought to topologically hold sister chromatids together from their synthesis in S phase until chromosome segregation in mitosis. How cohesin stably binds to chromosomes for extended periods, without impeding other chromosomal processes that also require access to the DNA, is poorly understood. Budding yeast cohesin is loaded onto DNA by the Scc2-Scc4 cohesin loader at centromeres and promoters of active genes, from where cohesin translocates to more permanent places of residence at transcription termination sites. Here we show that, at the GAL2 and MET17 loci, pre-existing cohesin is pushed downstream along the DNA in response to transcriptional gene activation, apparently without need for intermittent dissociation or reloading. We observe translocation intermediates and find that the distribution of most chromosomal cohesin is shaped by transcription. Our observations support a model in which cohesin is able to slide laterally along chromosomes while maintaining topological contact with DNA. In this way, stable cohesin binding to DNA and enduring sister chromatid cohesion become compatible with simultaneous underlying chromosomal activities, including but maybe not limited to transcription. PMID- 27278646 TI - The evolution of scale sensilla in the transition from land to sea in elapid snakes. AB - Scale sensilla are small tactile mechanosensory organs located on the head scales of many squamate reptiles (lizards and snakes). In sea snakes and sea kraits (Elapidae: Hydrophiinae), these scale organs are presumptive scale sensilla that purportedly function as both tactile mechanoreceptors and potentially as hydrodynamic receptors capable of sensing the displacement of water. We combined scanning electron microscopy, silicone casting of the skin and quadrate sampling with a phylogenetic analysis to assess morphological variation in sensilla on the postocular head scale(s) across four terrestrial, 13 fully aquatic and two semi aquatic species of elapids. Substantial variation exists in the overall coverage of sensilla (0.8-6.5%) among the species sampled and is broadly overlapping in aquatic and terrestrial lineages. However, two observations suggest a divergent, possibly hydrodynamic sensory role of sensilla in sea snake and sea krait species. First, scale sensilla are more protruding (dome-shaped) in aquatic species than in their terrestrial counterparts. Second, exceptionally high overall coverage of sensilla is found only in the fully aquatic sea snakes, and this attribute appears to have evolved multiple times within this group. Our quantification of coverage as a proxy for relative 'sensitivity' represents the first analysis of the evolution of sensilla in the transition from terrestrial to marine habitats. However, evidence from physiological and behavioural studies is needed to confirm the functional role of scale sensilla in sea snakes and sea kraits. PMID- 27278648 TI - The missing link: does tunnelling nanotube-based supercellularity provide a new understanding of chronic and lifestyle diseases? AB - Tunnelling nanotubes (TNTs) are increasingly recognized as central players in a multitude of cellular mechanisms and diseases. Although their existence and functions in animal organisms are still elusive, emerging evidence suggests that they are involved in developmental processes, tissue regeneration, viral infections or pathogen transfer, stem cell differentiation, immune responses as well as initiation and progression of neurodegenerative disorders and cancer (see Sisakhtnezhad & Khosravi 2015 Eur. J. Cell Biol. 94, 429-443. (doi:10.1016/j.ejcb.2015.06.010)). A broader field of vision, including their striking functional and structural resemblance with nanotube-mediated phenomena found throughout the phylogenetic tree, from plants down to bacteria, points to a universal, conserved and tightly regulated mechanism of cellular assemblies. Based on our initial definition of TNTs as open-ended channels mediating membrane continuity between connected cells (Rustom et al. 2004 Science 303, 1007-1010. (doi:10.1126/science.1093133)), it is suggested that animal tissues represent supercellular assemblies that-besides opening discrete communication pathways balance diverse stress factors caused by pathological changes or fluctuating physiological and environmental conditions, such as oxidative stress or nutrient shortage. By combining current knowledge about nanotube formation, intercellular transfer and communication phenomena as well as associated molecular pathways, a model evolves, predicting that the linkage between reactive oxygen species, TNT based supercellularity and the intercellular shuttling of materials will have significant impact on diverse body functions, such as cell survival, redox/metabolic homeostasis and mitochondrial heteroplasmy. It implies that TNTs are intimately linked to the physiological and pathological state of animal cells and represent a central joint element of diverse diseases, such as neurodegenerative disorders, diabetes or cancer. PMID- 27278649 TI - Connecting caddisworm silk structure and mechanical properties: combined infrared spectroscopy and mechanical analysis. AB - The underwater silk of an aquatic casemaking caddisfly larvae (Hesperophylax occidentalis) is viscoelastic, and displays distinct yield behaviour, large strain cycle hysteresis and near complete recovery of its initial strength and stiffness when unloaded. Yield followed by a stress plateau has been attributed to sequential rupture of serial Ca(2+)-cross-linked phosphoserine (pS) beta domains. Spontaneous recovery has been attributed to refolding of the Ca(2+)/pS domains powered by an elastic network. In this study, native Ca(2+) ions were exchanged with other metal ions, followed by combined mechanical and FTIR analysis to probe the contribution of pS/metal ion complexes to silk mechanical properties. After exchange of Ca(2+) with Na(+), the fibres are soft elastomers and the infrared spectra are consistent with Cv3 symmetry of the -[Formula: see text] groups. Multivalent metal ions decreased the -[Formula: see text] symmetry and the symmetric stretching modes (vs) split in a manner characteristic of ordered phosphate compounds, such as phosphate minerals and lamellar bilayers of phosphatidic acid lipids. Integrated intensities of the vs bands, indicative of the metal ion's effect on transition dipole moment of the P-O bonds, and thereby the strength of the phosphate metal complex, increased in the order: Na(+) < Mg(2+) < Sr(2+) < Ba(2+) < Ca(2+) < Eu(3+) < La(3+) < Zn(2+) < Fe(2+) With a subset of the metal ion series, the initial stiffness and yield stress of metal ion-exchanged fibres increased in the same order: [Formula: see text] [Formula: see text] establishing the link between phosphate transition dipole moments and silk fibre strength. PMID- 27278647 TI - Multidisciplinary approaches to understanding collective cell migration in developmental biology. AB - Mathematical models are becoming increasingly integrated with experimental efforts in the study of biological systems. Collective cell migration in developmental biology is a particularly fruitful application area for the development of theoretical models to predict the behaviour of complex multicellular systems with many interacting parts. In this context, mathematical models provide a tool to assess the consistency of experimental observations with testable mechanistic hypotheses. In this review, we showcase examples from recent years of multidisciplinary investigations of neural crest cell migration. The neural crest model system has been used to study how collective migration of cell populations is shaped by cell-cell interactions, cell-environmental interactions and heterogeneity between cells. The wide range of emergent behaviours exhibited by neural crest cells in different embryonal locations and in different organisms helps us chart out the spectrum of collective cell migration. At the same time, this diversity in migratory characteristics highlights the need to reconcile or unify the array of currently hypothesized mechanisms through the next generation of experimental data and generalized theoretical descriptions. PMID- 27278650 TI - Or47b plays a role in Drosophila males' preference for younger mates. AB - Reproductive behaviour is important for animals to keep their species existing on Earth. A key question is how to generate more and healthier progenies by choosing optimal mates. In Drosophila melanogaster, males use multiple sensory cues, including vision, olfaction and gustation, to achieve reproductive success. These sensory inputs are important, yet not all these different modalities are simultaneously required for courtship behaviour to occur. Moreover, the roles of these sensory inputs for male courtship choice remain largely unknown. Here, we demonstrate that males court younger females with greater preference and that olfactory inputs are indispensable for this male courtship choice. Specifically, the olfactory receptor Or47b is required for males to discriminate younger female mates from older ones. In combination with our previous work indicating that gustatory perception is necessary for this preference behaviour, our current study demonstrates the requirement of both olfaction and gustation in Drosophila males' courtship preference, thus providing new insights into the role of sensory cues in reproductive behaviour and success. PMID- 27278651 TI - Has the 'Fast-Track' referral system affected the route of presentation and/or clinical outcomes in patients with colorectal cancer? AB - BACKGROUND: The aim of this study is to determine whether the 'Fast-Track' referral system has changed the route by which patients present with colorectal cancer (CRC) and whether the route of presentation has any effect on clinical outcome. METHODS: A retrospective cohort study of patients diagnosed with CRC under the care of two consultant colorectal surgeons between April 2006 and December 2012. The route by which patients presented was categorised as Fast Track (FT), non-Fast-Track (non-FT) or acute. Outcome variables were operative intent, disease stage and 2- and 5-year survival. RESULTS: A total of 558 patients were identified. One hundred ninety-seven patients (35.3 %) were referred as FT, 108 (19.4 %) presented acutely and 253 patients (45.3 %) presented via other routes (non-FT). Over the study period, the route of presentation did not change significantly (P = 0.135). There was no significant difference between FT and non-FT groups in terms of the proportion of patients undergoing potentially curative surgery (70.6 vs 74.3 %, P = 0.092) or with node negative disease (48.2 vs 52.2 %, P = 0.796) nor was there any difference in 2 year or 5-year survival (74.1 vs 73.9 %, P = 0.837 and 52.3 vs 53.8 %, P = 0.889, respectively). Patients who presented acutely were less likely to undergo curative resection, had more advanced disease and had worse 2- and 5-year survival. CONCLUSIONS: The Fast-Track referral system has not affected the route by which patients present with CRC nor has it had any effect on clinical outcomes. Alternative strategies are required if the desired improvement in outcomes is to be achieved. PMID- 27278652 TI - The vascular laboratory. PMID- 27278653 TI - Conceptualizing Internet use disorders: Addiction or coping process? AB - This paper problematizes the tendency to study Internet use disorders from a perspective of addiction. It is argued that an addiction perspective, grounded in our understanding of substance use disorders, has not contributed much to an improved understanding of the antecedents and etiology of Internet use disorders. Despite this, researchers continue to frame Internet use disorders as an addiction, recently exemplified by the inclusion of Internet gaming disorder in the DSM-5 research appendix as a behavioral addiction. This paper claims that the decision to use an addiction framework to study Internet use disorders has consequences for the way in which results are interpreted, which impacts the potential for theoretical and etiological contributions negatively. The paper argues that a perspective of addiction may not be the most useful approach because it causes a mismatch between theory and findings in empirical work: it is not uncommon to find that a study is positioned as a study of addiction, but presents findings more illustrative of coping behaviors. The paper draws on two examples from the literature to illustrate this mismatch and discusses how this hinders theoretical and etiological development. The question that is asked going forward is what alternative explanations we might identify by not exclusively adhering to an addiction framework for purposes of research. Recommendations are given for how to usefully approach the study of Internet use disorders outside a framework of addiction. It also discusses how scholars who still prefer a framework of addiction might strengthen their conceptual position to ensure improved contributions to etiology and theoretical development. PMID- 27278654 TI - Enhanced loading regimen of teicoplanin is necessary to achieve therapeutic pharmacokinetics levels for the improvement of clinical outcomes in patients with renal dysfunction. AB - We evaluated the clinical efficacy and safety of teicoplanin according to the pharmacokinetics (PK) therapeutic level achieved in patients with renal dysfunction. Target trough concentration (Cmin) was >=15-30 MUg/ml which has been recommended in patients with normal renal function. Adult patients (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)) who were treated by teicoplanin were included in the study. We adopted two types of regimen for the initial 3 days: the conventional regimen, and the enhanced loading regimen (10 mg/kg twice daily on the 1st day, followed by 6.7-10 mg/kg once daily for the 2nd and 3rd days]. Two hundred and eighty-eight patients were evaluated for safety, and 106 patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were evaluated for clinical efficacy. A significantly higher success rate was obtained in patients who achieved the target initial Cmin compared with those that did not (75.0 % vs 50.0 %, p = 0.008). In a multivariate analysis, initial Cmin >=15 MUg/ml was an independent factor for clinical success (adjusted odds ratio: 4.20, 95 % confidence interval: 1.34-13.15). In patients with 15-30 MUg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 MUg/ml. In conclusion, achievement of Cmin of 15-30 MUg/ml without delay was necessary to improve clinical outcomes for the treatment by teicoplanin in patients with renal dysfunction. Further investigation is required regarding the optimal loading regimen to achieve the therapeutic levels in those patients. PMID- 27278655 TI - A prospective longitudinal study of tuberculosis among household contacts of smear-positive tuberculosis cases in Lima, Peru. AB - BACKGROUND: Household contacts (HHCs) of TB cases are at increased risk for TB disease compared to the general population but the risk may be modified by individual or household factors. We conducted a study to determine incident TB among HHCs over two years after exposure and to identify individual and household level risk factors. METHODS: Adults newly diagnosed with a first episode of smear positive pulmonary TB (index cases) between March 2010 and December 2011 in eastern Lima, were interviewed to identify their HHC and household characteristics. TB registers were reviewed for up to two years after the index case diagnosis and house visits were made to ascertain TB cases among HHC. The TB incidence rate ratio among HHCs as a function of risk factors was determined using generalized linear mixed models. RESULTS: The 1178 index cases reported 5466 HHCs. In 402/1178 (34.1 %) households, at least one HHC had experienced a TB episode ever. The TB incidence among HHCs was 1918 (95%CI 1669-2194) per 100,000 person-years overall, and was 2392 (95%CI 2005-2833) and 1435 (95%CI 1139-1787) per 100,000 person-years in the first and second year, respectively. Incident TB occurred more than six months following the index case's TB diagnosis in 121/205 (59.0 %) HHCs. In HHCs, bacillary load and time between symptoms and treatment initiation in the index case, as well as the relationship to the index case and the sex of the HHC all had a significant association with TB incidence in HHCs. CONCLUSIONS: Incidence of TB among HHCs was more than ten times higher than in the general population. Certain HHC and households were at higher risk of TB, we recommend studies to compare HHC investigation to households at highest risk versus current practice, in terms of efficiency. PMID- 27278656 TI - Immediate effects of alcohol marketing communications and media portrayals on consumption and cognition: a systematic review and meta-analysis of experimental studies. AB - BACKGROUND: Restricting marketing of alcoholic products is purported to be a cost effective intervention to reduce alcohol consumption. The strength of evidence supporting this claim is contested. This systematic review aimed to assess immediate effects of exposure to alcohol marketing on alcoholic beverage consumption and related cognitions. METHODS: Electronic searches of nine databases, supplemented with reference list searches and forward citation tracking, were used to identify randomised, experimental studies assessing immediate effects of exposure to alcohol marketing communications on objective alcohol consumption (primary outcome), explicit or implicit alcohol-related cognitions, or selection without purchasing (secondary outcomes). Study limitations were assessed using the Cochrane Risk of Bias tool. Random and fixed effects meta-analyses were conducted to estimate effect sizes. RESULTS: Twenty four studies met the eligibility criteria. A meta-analysis integrating seven studies (758 participants, all students) found that viewing alcohol advertisements increased immediate alcohol consumption relative to viewing non alcohol advertisements (SMD = 0.20, 95 % CI = 0.05, 0.34). A meta-analysis integrating six studies (631 participants, all students) did not find that viewing alcohol portrayals in television programmes or films increased consumption (SMD = 0.16, 95 % CI = -0.05, 0.37). Meta-analyses of secondary outcome data found that exposure to alcohol portrayals increased explicit alcohol related cognitions, but did not find that exposure to alcohol advertisements influenced explicit or implicit alcohol-related cognitions. Confidence in results is diminished by underpowered analyses and unclear risk of bias. CONCLUSIONS: Viewing alcohol advertisements (but not alcohol portrayals) may increase immediate alcohol consumption by small amounts, equivalent to between 0.39 and 2.67 alcohol units for males and between 0.25 and 1.69 units for females. The generalizability of this finding beyond students and to other marketing channels remains to be established. PMID- 27278657 TI - JAK3-STAT pathway blocking benefits in experimental lupus nephritis. AB - BACKGROUND: Lupus nephritis (LN) is a complex chronic autoimmune disease of unknown etiology characterized by loss of tolerance against several self antigens. Cytokines are known to be central players in LN pathogenesis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is one important pathway that mediates signal transduction of several cytokines. In this study, we examined the pathogenic role of this pathway and how CP-690,550 treatment influences LN outcome. METHODS: Six-month-old NZB/NZWF1 mice were divided into two different treatment groups: (1) control animals given vehicle treatment, cyclophosphamide, and mycophenolate mofetil treatment as positive controls of the therapy and (2) mice treated with CP-690,550, a JAK3 inhibitor. Mice were treated for 12 weeks. We evaluated renal function, anti-double-stranded DNA (anti-dsDNA) antibody, renal histology changes, kidney complement and immunoglobulin G (IgG) deposits, T-cell and macrophage infiltration, kidney inflammatory gene expression, and circulating cytokine changes. RESULTS: CP 690,550 treatment significantly reduced proteinuria and improved renal function and histological lesions of the kidney. Compared with vehicle-treated animals, those undergoing CP-690,550 treatment showed significantly diminished anti-dsDNA antibody and complement component C3 and IgG deposition in glomeruli. We also observed a significant reduction of T-cell and macrophage infiltration. Kidney gene expression revealed a reduction in inflammatory cytokines and complement and related macrophage-attracting genes. Circulating inflammatory cytokines were also reduced with treatment. CONCLUSIONS: On the basis of our results, we conclude that the JAK-STAT pathway is implicated in the progression of renal inflammation in NZB/WF1 mice and that targeting JAK3 with CP-690,550 is effective in slowing down the course of experimental LN. Thus, CP-690,550 could become a new therapeutic tool in LN and other autoimmune diseases. PMID- 27278658 TI - Heterogeneous contraction of the left ventricle demonstrated by 2-dimensional strain imaging. AB - BACKGROUND: Tissue Doppler imaging (TDI) is useful in quantifying regional myocardial function, but has a significant limitation of Doppler angle dependency. The recently developed 2-dimensional strain imaging (2DS), based on speckle tracking imaging (STI) technology, enables us to evaluate myocardial function independent of ultrasound beam direction. The aim of this study was to assess the mode of contraction of the left ventricle. METHODS: Circumferential, radial and longitudinal strains were measured in 18 segments (anteroseptal, anterior, anterolateral, inferolateral, inferior and inferoseptal walls at the base, mid-ventricle and apex) from apical and short-axis views using 2DS in 24 healthy subjects (mean age, 33 +/- 5 years). We divided the left ventricle into 2 sites: septum (anterior, anteroseptal and inferoseptal walls) and free walls (anterolateral, inferolateral and inferior walls). We then compared the mode of contraction between the septum and free walls. RESULTS: At the base and mid ventricular levels, circumferential strain was larger in the septum (-22.6 +/- 3.6 vs. -18.3 +/- 4.1% and -24.1 +/- 4.8 vs. -18.4 +/- 5.7%, respectively; p < 0.0001 each), and radial strain was larger in the free walls (33.4 +/- 12.4 vs. 38.7 +/- 14.5% and 37.8 +/- 12.6 vs. 43.0 +/- 11.6%, respectively; p < 0.001 each) at the basal and mid-ventricular levels, whereas both were relatively homogeneous at the apex. The longitudinal strain did not differ among walls. CONCLUSIONS: Heterogeneous contraction is seen in the left ventricle. The septum mainly contracts circumferentially, whereas the free walls contract radially. 2DS is helpful in understanding the mode of 3-dimensional myocardial contraction. PMID- 27278659 TI - Gender differences of pulsed and tissue Doppler indexes of left ventricular diastolic function in healthy subjects. AB - BACKGROUND: The purpose of this study is to determine the normative Doppler values and gender differences in left ventricular (LV) diastolic function in healthy subjects at each decade of life. METHODS: Four hundred sixty-seven male and 455 female healthy subjects, aged 20-90 years, underwent standard echocardiography and tissue Doppler imaging. We divided the subjects into seven groups, based on the decade of their age (i.e., 20s, 30s, 40s, 50s, 60s, 70s, and 80s), and measured standard echocardiographic parameters and Doppler indices. RESULTS: Females younger than 50 years had significantly higher mitral E velocity, and females older than 40 years had significantly higher mitral A velocity, compared with their male counterparts. There was no difference in mitral E to A velocity ratio (E/A) at any age. The tissue Doppler method showed significantly lower early diastole velocity of the mitral annulus (E a) in females-especially females older than 50 years-than in males (10.7 +/- 3.7 versus 11.2 +/- 3.7 cm/s, p < 0.025). Mean E/E a ratio was higher in females than in males (6.9 +/- 2.4 versus 6.0 +/- 2.0, p < 0.0001). CONCLUSION: Our results indicate gender differences in Doppler indexes of LV diastolic function in healthy subjects. In clinical settings, assessment of LV diastolic function using the Doppler method should take into account patient gender. PMID- 27278660 TI - Diastolic flow velocity pattern of the left anterior descending coronary artery in hypertrophied heart, with special reference to the difference between hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy. AB - BACKGROUND: This study aimed to clarify the characteristics of diastolic flow velocity pattern of the left anterior descending coronary artery (LAD) in patients with left ventricular hypertrophy (LVH), and the difference in diastolic LAD flow velocity pattern between hypertensive LVH and hypertrophic cardiomyopathy (HCM). METHODS: The flow velocity pattern was recorded at the mid portion of the LAD by high-frequency transthoracic Doppler echocardiography in 22 patients with HCM, 10 hypertensive patients with LVH [LVH(+)HT], and 9 hypertensive patients without LVH [LVH(-)HT]. The diastolic flow pattern was analyzed. Standard two-dimensional echocardiogram and apexcardiogram (ACG) were also recorded. RESULTS: The interventricular septal thickness (IVST) and the sum of the IVST and LV posterior wall thickness (PWT) (IVST + PWT) were greater in HCM than in HT (p < 0.01) patients. Early diastolic upstroke time (D-UT) of the LAD flow velocity wave was longest in HCM, and was longer in LVH(+)HT than in LVH(-)HT (p < 0.01) patients. Direct correlation was found between D-UT and IVST, IVST + PWT in patients with LVH(+)HT and LVH(-)HT (r = 0.80, 0.79, respectively; p < 0.01), but no correlation was found between these parameters in HCM. Late diastolic step (LDS) formation of the LAD flow velocity wave was observed in 68% of HCM, 20% of LVH(+)HT, but none of the LVH(-)HT patients. The A wave ratio of ACG was higher in patients with LDS than in those without (p < 0.01). The LDS occurred coincidently with the A wave of ACG. CONCLUSIONS: The diastolic LAD flow velocity pattern in hypertrophied heart is characterized by slow acceleration and LDS formation, reflecting impaired relaxation and increased stiffness of the LV, respectively. These abnormalities correlate with the degree of hypertrophy in hypertensive heart, but do not correlate with that in HCM. PMID- 27278662 TI - Prenatally diagnosed hypoplastic left heart syndrome with intact atrial septum and ventriculocoronary arterial fistula. AB - Intact atrial septum (IAS) and left ventriculocoronary arterial fistula (LVCAF) are the significant risk factors of hypoplastic left heart syndrome (HLHS), and when they are present, prognosis is grim. We report a case of prenatally diagnosed HLHS with IAS and LVCAF that was treated with surgical atrial septostomy and bilateral pulmonary arterial banding (BPAB) immediately after birth. The Doppler flow pattern of left anterior descending coronary artery (LAD) with dominant retrograde flow was normalized after atrial-septostomy with decompression of left atrial (LA) hypertension. This is the first report showing the influence of atrial-septostomy on coronary flow in HLHS patient with LVCAF. PMID- 27278661 TI - End-systolic and end-diastolic left atrial volume assessment by two-dimensional echocardiography: a comparison study with magnetic resonance imaging. AB - BACKGROUND: The left atrial volume (LAV) is an important indicator of the severity of certain diseases, and measuring LAV through the cardiac cycle may enable the evaluation of various left atrium (LA) functional parameters. The results of two-dimensional (2D) echocardiographic LAV measurement methods vary, and no technique is accepted as being optimal. OBJECTIVE: This study compared the accuracy of end-systolic and end-diastolic LAV measurements by 2D echocardiography with those obtained by magnetic resonance imaging (MRI). METHODS: Fifty consecutive patients who underwent both echocardiography and MRI due to clinical reasons with nonselective cardiac disease were studied. LAVs by 2D echocardiography were obtained with the prolate ellipsoid (PE), biplane area length (AL), and modified Simpson's (MS) methods. RESULTS: End-systolic and end diastolic LAVs calculated by each method correlated significantly with MRI results (P < 0.0001). The prolate ellipsoid method provided LAVs that most correlated with MRI results, and the biplane area-length and modified Simpson's methods provided LAVs with small mean differences (<5 ml) compared to MRI results. CONCLUSION: All three methods of 2D echocardiographic LAV measurement provide valuable LAV data, suggesting the possibility of evaluating various LA functional parameters. PMID- 27278663 TI - Rapidly progressing multiple cardiac rhabdomyosarcoma. PMID- 27278664 TI - Neural pathways in processing of sexual arousal: a dynamic causal modeling study. AB - Three decades of research have investigated brain processing of visual sexual stimuli with neuroimaging methods. These researchers have found that sexual arousal stimuli elicit activity in a broad neural network of cortical and subcortical brain areas that are known to be associated with cognitive, emotional, motivational and physiological components. However, it is not completely understood how these neural systems integrate and modulated incoming information. Therefore, we identify cerebral areas whose activations were correlated with sexual arousal using event-related functional magnetic resonance imaging and used the dynamic causal modeling method for searching the effective connectivity about the sexual arousal processing network. Thirteen heterosexual males were scanned while they passively viewed alternating short trials of erotic and neutral pictures on a monitor. We created a subset of seven models based on our results and previous studies and selected a dominant connectivity model. Consequently, we suggest a dynamic causal model of the brain processes mediating the cognitive, emotional, motivational and physiological factors of human male sexual arousal. These findings are significant implications for the neuropsychology of male sexuality. PMID- 27278665 TI - Comorbid Depression and Other Predictors of PTSD Severity in Urban Public Transit Employees. AB - The purpose of the study was to determine whether post traumatic stress disorder (PTSD) with Major Depressive Disorder (MDD) among urban public transit employees who were exposed to a workplace traumatic event is associated with greater PTSD severity over the 6-month follow-up period compared to PTSD without MDD, and also to identify predictors of PTSD severity among these employees. Information about Axis-I diagnosis and PTSD severity were collected from the SCID-I and the Modified PTSD Symptom Scale (MPSS) respectively. PTSD without MDD (N = 29) and PTSD with MDD (N = 37) groups were not significantly different in terms of PTSD severity. The severity of depression (p = 0.01), female (p = 0.01), non-Caucasian (p = 0.01), perceived high workplace related stress (p = 0.02), and history of lifetime trauma (p = 0.01) were significantly associated with greater PTSD severity after controlling other variables. This study highlights the importance of modifiable variables for reducing PTSD severity after a workplace traumatic event in transit employees. PMID- 27278666 TI - Bone marrow transplantation versus immunosuppressive therapy in patients with acquired severe aplastic anemia. AB - Standard front-line treatment for acquired aplastic anemia (AA) for patients is either immunosuppressive therapy (IST) or bone marrow transplantation (BMT), usually from an HLA identical sibling. Whereas long-term survival is comparable with either treatment, important differences remain: IST patients may have incomplete or no recovery, are exposed to late clonal disorders and relapse of the original disease. Transplantation is a curative treatment, but patients are exposed to transplant-related complications both acute and chronic, such as chronic graft versus host disease (cGvHD). In the year 2000, a study by the European Group for Blood and Marrow Transplantation (EBMT), looked at failure free survival (FFS), in patients receiving first-line BMT from an HLA identical sibling, or the first-line IST. Young patients with low neutrophil counts benefited of the first-line BMT; the opposite was true for older patients with higher neutrophil counts; and a third intermediate group of patients had comparable survival irrespective of the first-line therapy. We have now studied a more recent cohort of patients to assess whether things have changed over the years. We have found similar results, although overall survival has improved, as a consequence of changes in the IST and BMT protocols. PMID- 27278667 TI - Benefit of uridine triacetate (Vistogard) in rescuing severe 5-fluorouracil toxicity in patients with dihydropyrimidine dehydrogenase (DPYD) deficiency. AB - BACKGROUND: 5-Fluorouracil (5-FU), an analog of uracil, is one of the most commonly used chemotherapeutic agents and like other agents has a narrow therapeutic index limited by toxicity. Compared to previous attempts, uridine triacetate (Vistogard) has shown to increase the potential efficacy of 5-FU by allowing administering a higher dose and decreasing the toxicity. Recently, Vistogard received orphan drug designation from the FDA as an antidote in the treatment of 5-FU poisoning and from the European Medicines Agency as a treatment for 5-FU overdose. However, no data have been published to date in humans who were rescued by this agent following severe toxicity associated with 5-FU due to dihydropyrimidine dehydrogenase (DPYD) deficiency, the enzyme which is responsible for the elimination of approximately 80 % of the administered dose of 5-FU. PATIENTS AND METHODS: We identified two patients with advanced pancreatic cancer who were referred to us for testing of DPYD status following severe toxicity associated with 5-FU administered at a dose of 1400 mg/m(2) weekly bolus high-dose 5-FU followed by oral uridine triacetate as a part of a clinical trail. One patient developed grade 3 thrombocytopenia and grade 3 skin rash that resolved with discontinuation of 5-FU and supportive care, while second patient developed grade 4 thrombocytopenia, grade 3 coagulopathy and grade 3 neurological toxicity with a fatal outcome. DPYD status was evaluated as we have previously published. RESULTS: The first patient was found to have an abnormally low DPYD activity of 0.087-nmol/min/mg protein by radioisotopic assay (reference normal range 0.182-0.688 nmol/min/mg protein). Because of pancytopenia, DPYD enzyme activity could not be assessed in patient 2; genotypic analysis of DPYD during autopsy revealed the presence of the heterozygous mutation, IVS14+1 G>A, DPYD*2A, now recognized as the most common cause of DPYD deficiency. CONCLUSION: These two patients present the first two cases of DPYD deficiency that had either delay in severe toxicity or recovered from severe toxicity as they received oral Vistogard as a part of the conical trial. Toxicity was delayed in both patients by a mean of 3.5 weeks (range 3-4 weeks), indicating that Vistogard might be able to delay 5-FU toxicity despite higher doses than standard bolus dose of 5-FU used in gastrointestinal malignancies and the appearance of a potentially less toxic adverse effect of 5-FU at an unusual site (cutaneous) in one patient. The role of uridine triacetate with 5-FU in DPYD-deficient patients needs further investigation. PMID- 27278668 TI - Pharmacokinetics and safety of vitamin E delta-tocotrienol after single and multiple doses in healthy subjects with measurement of vitamin E metabolites. AB - PURPOSE: Vitamin E delta-tocotrienol (VEDT) has demonstrated chemopreventive and antineoplastic activity in preclinical models. The aim of our study was to determine the safety and pharmacokinetics of VEDT and its metabolites after single- and multiple-dose administrations in healthy subjects. METHODS: Thirty six subjects received from 100 to 1600 mg of oral VEDT as a single dose or twice daily for 14 consecutive days. A 3 + 3 dose escalation design was utilized. Pharmacokinetic data were derived from high-performance liquid chromatography (HPLC) assays. Serial blood and urine samples were collected before and during VEDT administration, with serum and urine metabolites assessed using HPLC. RESULTS: No drug-related adverse events were observed. Pharmacokinetic parameters for single and multiple doses were, respectively, as follows (shown as range): time to maximum concentration of 4-9.3 and 4.7-7.3 h, maximum concentration of 795.6-3742.6 and 493.3-3746 ng/mL, half-life of 1.7-5.9 and 2.3-6.9 h, and 0-12 h area under the curve of 4518.7-20,781.4 and 1987.7-22,171.2 ng h/mL. Plasma tocotrienols were significantly increased after VEDT administration, indicating oral bioavailability of VEDT in humans. Plasma and urine levels of metabolites, delta-carboxyethyl hydroxychroman, and delta-carboxymethylbutyl hydroxychroman were elevated after VEDT administration in a dose-dependent manner and were 30-60 times significantly higher than delta-tocotrienol levels. VEDT can be safely administered at doses up to 1600 mg twice daily. Plasma VEDT concentrations were comparable to those obtained in VEDT-treated mice in which tumor growth was delayed. CONCLUSIONS: Our results suggest that VEDT can be safely consumed by healthy subjects and achieve bioactive levels, supporting the investigation of VEDT for chemoprevention. PMID- 27278669 TI - Genomic leftovers: identifying novel microsatellites, over-represented motifs and functional elements in the human genome. AB - The human genome is 99% complete. This study contributes to filling the 1% gap by enriching previously unknown repeat regions called microsatellites (MST). We devised a Global MST Enrichment (GME) kit to enrich and nextgen sequence 2 colorectal cell lines and 16 normal human samples to illustrate its utility in identifying contigs from reads that do not map to the genome reference. The analysis of these samples yielded 790 novel extra-referential concordant contigs that are observed in more than one sample. We searched for evidence of functional elements in the concordant contigs in two ways: (1) BLAST-ing each contig against normal RNA-Seq samples, (2) Checking for predicted functional elements using GlimmerHMM. Of the 790 concordant contigs, 37 had an exact match to at least one RNA-Seq read; 15 aligned to more than 100 RNA-Seq reads. Of the 249 concordant contigs predicted by GlimmerHMM to have functional elements, 6 had at least one exact RNA-Seq match. BLAST-ing these novel contigs against all publically available sequences confirmed that they were found in human and chimpanzee BAC and FOSMID clones sequenced as part of the original human genome project. These extra-referential contigs predominantly contained pentameric repeats, especially two motifs: AATGG and GTGGA. PMID- 27278670 TI - Development and feasibility of the Help to Overcome Problems Effectively (HOPE) self-management intervention for people living with multiple sclerosis. AB - PURPOSE: To describe the development and feasibility of a self-management intervention called the Help to Overcome Problems Effectively (HOPE: MS), aimed at improving the physical and psychological wellbeing of people living with Multiple Sclerosis (MS). METHOD: HOPE: MS is an innovative, 6-week group-based, manualised self-management intervention combining positive psychology theory and practice, and cognitive behavioural therapy (CBT). Participants (N = 21) recruited via a local East Midlands branch of the MS Society attended one of three HOPE: MS interventions and completed self-reported outcome measures in week 1 and week 6. The following outcome measures were used: The Multiple Sclerosis Impact Scale; Multiple Sclerosis Fatigue Severity Scale; The Multiple Sclerosis Self-Efficacy Scale; The Adult State Hope Scale; The Hospital Anxiety and Depression Scale; The Positive and Negative Affect Scale. RESULTS: Post intervention (6 weeks) mean scores decreased in the physical impact (baseline M = 65.6, SD = 17.4; 6 weeks M = 55.1, SD = 17.9, 95% CI [-4.39, -16.47] and the psychological impact of MS (baseline M = 24.0, SD = 7.3; 6 weeks M = 18.9; SD = 6.3, 95% CI [-2.54, -7.66]). There was also a decrease mean fatigue severity scores (baseline 49.4, SD = 13.3, 6 weeks M = 41.1, SD = 14.4, 95% CI [-2.65, 13.44]). There was a mean decrease in depression scores (baseline M = 6.9, SD = 3.5; 6 weeks M = 4.2, SD = 2.8, 95% CI [-1.43, -4.00]). There were smaller mean decreases in anxiety (baseline M = 7.6, SD = 3.4; 6 weeks M = 6.7 (4.0), 95% CI [0.69, -2.50]) and negative affect (baseline M = 22.9, SD = 6.8; 6 weeks M = 20.8 (8.1), 95% CI [0.69, -2.50]) refer Table 3 ). Mean MS self-efficacy scores (baseline 21.7, SD = 4.2; 6 weeks M = 24.1, SD = 4.7, 95% CI [0.23, 4.53]), mean total hope scores (baseline M = 23.3, SD = 10.7; 6 weeks M = 32.2 (10.6), 95% CI [4.91, 12.9]), hope agency scores (baseline M = 10.5, SD = 5.7; 6 weeks M = 15.7 (6.2), 95% CI [2.37, 8.01]), hope pathways (baseline M = 12.9, SD = 6.0; 6 weeks M = 16.6 (4.9), 95% CI [2.00, 5.43]) and positive affect scores increased (baseline M = 27.3, SD = 7.1; 6 months M = 32.2, SD = 8.4, 95% CI [0.42, 9.39]). Participants positively rated the intervention quality and delivery. CONCLUSIONS: This feasibility study showed that the HOPE: MS was acceptable and useful to people living with MS. Further robust evaluations using a randomised controlled trial design with longer follow ups are needed to confirm early promising results of the HOPE: MS. Implications for rehabilitation Living with MS requires constant adjustments to cope with unpredictable symptoms. Self-management interventions have the potential to help people living with MS to improve their quality of life. A feasibility study of the HOPE: MS self-management group-based intervention showed that it was acceptable and useful to people living with MS. PMID- 27278672 TI - An integrative model of the impairments in insight in schizophrenia: emerging research on causal factors and treatments. AB - INTRODUCTION: Poor insight, or unawareness of some major aspect of mental illness, is a major barrier to wellness when it interferes with persons seeking out treatment or forming their own understanding of the challenges they face. One barrier to addressing impaired insight is the absence of a comprehensive model of how poor insight develops. AREAS COVERED: To explore this issue we review how poor insight is the result of multiple phenomena which interfere with the construction of narrative accounts of psychiatric challenges, rather than a single social or biological cause. Expert commentary: We propose an integrative model of poor insight in schizophrenia which involves the interaction of symptoms, deficits in neurocognition, social cognition, metacognition, and stigma. Emerging treatments for poor insight including therapies which focus on the development of metacognition are discussed. PMID- 27278673 TI - Defect in ND2, COX2, ATP6 and COX3 mitochondrial genes as a risk factor for canine mammary tumour. AB - The aim of this study was to identify mutations in ND2, COX2, ATP6 and COX3 mitochondrial genes in canine mammary tumour, determine their association with the process of neoplastic transformation, and phenotypic traits of dogs. In total, 93 biological samples, including blood, normal and neoplastic tissue samples from 31 dogs with diagnosed malignant canine mammary tumours were analysed. DNA sequencing of genes as well as bioinformatics and statistical analyses were performed. A total of 28 polymorphic loci and 11 mutations were identified. One of the mutations was blood heteroplasmy and two of the mutations caused an amino acid change in p.N117S and p.A184T. For the first time, mutations in mitochondrial genes were detected in dogs with mammary tumours. A statistically significant association between the presence of mutations and the size and age of dogs was demonstrated. Some of these changes may imply that these are the hotspot mutations of canine mammary tumour. PMID- 27278671 TI - Gender differences in murine pulmonary responses elicited by cellulose nanocrystals. AB - BACKGROUND: Cellulose-based materials have been used for centuries to manufacture different goods derived from forestry and agricultural sources. In the growing field of nanocellulose applications, its uniquely engineered properties are instrumental for inventive products coming to competitive markets. Due to their high aspect ratio and stiffness, it is speculated that cellulose nanocrystals (CNC) may cause similar pulmonary toxicity as carbon nanotubes and asbestos, thus posing a potential negative impact on public health and the environment. METHODS: The present study was undertaken to investigate the pulmonary outcomes induced by repeated exposure to respirable CNC. C57BL/6 female and male mice were exposed by pharyngeal aspiration to CNC (40 MUg/mouse) 2 times a week for 3 weeks. Several biochemical endpoints and pathophysiological outcomes along with gene expression changes were evaluated and compared in the lungs of male and female mice. RESULTS: Exposure to respirable CNC caused pulmonary inflammation and damage, induced oxidative stress, elevated TGF-beta and collagen levels in lung, and impaired pulmonary functions. Notably, these effects were markedly more pronounced in females compared to male mice. Moreover, sex differences in responses to pulmonary exposure to CNC were also detected at the level of global mRNA expression as well as in inflammatory cytokine/chemokine activity. CONCLUSIONS: Overall, our results indicate that there are considerable differences in responses to respirable CNC based on gender with a higher pulmonary toxicity observed in female mice. PMID- 27278674 TI - Letter to the Editor: Does Degenerative Lumbar Spine Disease Influence Femoroacetabular Flexion in Patients Undergoing Total Hip Arthroplasty? PMID- 27278676 TI - CORR Insights((r)): The ACS NSQIP Risk Calculator Is a Fair Predictor of Acute Periprosthetic Joint Infection. PMID- 27278675 TI - Disparities in TKA Outcomes: Census Tract Data Show Interactions Between Race and Poverty. AB - BACKGROUND: Race is an important predictor of TKA outcomes in the United States; however, analyses of race can be confounded by socioeconomic factors, which can result in difficulty determining the root cause of disparate outcomes after TKA. QUESTIONS/PURPOSES: We asked: (1) Are race and socioeconomic factors at the individual level associated with patient-reported pain and function 2 years after TKA? (2) What is the interaction between race and community poverty and patient reported pain and function 2 years after TKA? METHODS: We identified all patients undergoing TKA enrolled in a hospital-based registry between 2007 and 2011 who provided 2-year outcomes and lived in New York, Connecticut, or New Jersey. Of patients approached to participate in the registry, more than 82% consented and provided baseline data, and of these patients, 72% provided 2-year data. Proportions of patients with complete followup at 2 years were lower among blacks (57%) than whites (74%), among patients with Medicaid insurance (51%) compared with patients without Medicaid insurance (72%), and among patients without a college education (67%) compared with those with a college education (71%). Our final study cohort consisted of 4035 patients, 3841 (95%) of whom were white and 194 (5%) of whom were black. Using geocoding, we linked individual-level registry data to US census tracts data through patient addresses. We constructed a multivariate linear mixed-effect model in multilevel frameworks to assess the interaction between race and census tract poverty on WOMAC pain and function scores 2 years after TKA. We defined a clinically important effect as 10 points on the WOMAC (which is scaled from 1 to 100 points, with higher scores being better). RESULTS: Race, education, patient expectations, and baseline WOMAC scores are all associated with 2-year WOMAC pain and function; however, the effect sizes were small, and below the threshold of clinical importance. Whites and blacks from census tracts with less than 10% poverty have similar levels of pain and function 2 years after TKA (WOMAC pain, 1.01 +/- 1.59 points lower for blacks than for whites, p = 0.53; WOMAC function, 2.32 +/- 1.56 lower for blacks than for whites, p = 0.14). WOMAC pain and function scores 2 years after TKA worsen with increasing levels of community poverty, but do so to a greater extent among blacks than whites. Disparities in pain and function between blacks and whites are evident only in the poorest communities; decreasing in a linear fashion as poverty increases. In census tracts with greater than 40% poverty, blacks score 6 +/- 3 points lower (worse) than whites for WOMAC pain (p = 0.03) and 7 +/- 3 points lower than whites for WOMAC function (p = 0.01). CONCLUSIONS: Blacks and whites living in communities with little poverty have similar patient reported TKA outcomes, whereas in communities with high levels of poverty, there are important racial disparities. Efforts to improve TKA outcomes among blacks will need to address individual- and community-level socioeconomic factors. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27278677 TI - Hips With Protrusio Acetabuli Are at Increased Risk for Failure After Femoroacetabular Impingement Surgery: A 10-year Followup. AB - BACKGROUND: Protrusio acetabuli is a rare anatomic pattern of the hip in which the femoral head protrudes into the true pelvis. The increased depth of the hip and the excessive size of the lunate surface typically lead to severe pincer-type femoroacetabular impingement (FAI); however, to our knowledge, there are no published mid- or long-term studies on results of circumferential acetabular rim trimming through a surgical hip dislocation for patients with this condition. QUESTIONS/PURPOSES: (1) What is the 10-year survivorship of the hips treated with circumferential rim trimming through a surgical hip dislocation compared with a control group of hips that underwent surgery for pincer FAI but that did not have protrusio acetabuli? (2) What are the factors that were associated with a decreased likelihood of survivorship in those hips with the following endpoints: total hip arthroplasty, Merle d'Aubigne score of less than 15, and/or radiographic progression of osteoarthritis (OA)? (3) Does the radiographic pattern of degeneration differ between the two groups? METHODS: We performed a case-control study comparing two groups: a protrusio group (32 patients [39 hips]) and a control group (66 patients [86 hips]). The control group consisted of hips treated with a surgical hip dislocation for pincer FAI and did not include hips with a positive protrusio sign or a lateral center-edge angle > 39 degrees . The study group did not differ from the control group regarding the preoperative Tonnis OA score, age, and body mass index. However, the study group had more women, decreased mean height and weight, and lower preoperative Merle d'Aubigne-Postel scores, which were inherent differences at the time of first presentation. During the period in question, the indication for performing these procedures was a painfully restricted range of motion in flexion and internal rotation (positive impingement sign). The mean followup of the protrusio group (9 +/- 5 years [range, 2-18 years]) did not differ from the control group (11 +/- 1 years [range, 10-13 years], p = 0.109). At the respective minimum followup intervals in the underlying database from which cases and control subjects were drawn, followup was 100% for patients with protrusion who underwent FAI surgery and 97% for patients with FAI who underwent surgery for other anatomic patterns (three of 86 hips). We assessed the Merle d'Aubigne-Postel score, Harris hip score, WOMAC, and UCLA activity score at latest followup. A Kaplan-Meier survivorship analysis of the hip was calculated if any of the following endpoints for both groups occurred: conversion to total hip arthroplasty, a Merle d'Aubigne Postel score < 15, and/or radiographic progression of OA. Differences in survivorship were analyzed using the log-rank test. RESULTS: At 10-year followup, we found a decreased survivorship of the hip for the protrusio group (51% [95% confidence interval {CI}, 34%-67%]) compared with the control group (83% [95% CI, 75%-91%], p < 0.001) with one or more of the endpoints stated. We found four multivariate factors associated with a decreased likelihood of survival of the native hip according to the mentioned endpoints: body mass index > 25 kg/m(2) (adjusted hazard ratio, 6.4; 95% CI, 5.2-8.1; p = 0.009), a preoperative Tonnis OA score >= 1 (13.3; 95% CI, 11.8-14.9; p = 0.001), a postoperative lateral center-edge angle > 40 degrees (4.2; 95% CI, 2.8-5.6; p = 0.042), and a postoperative posterior coverage > 56% (6.0; 95% CI, 4.3-7.6; p = 0.037). Preoperatively, joint space narrowing and osteophytes were more frequent posteroinferior (joint space narrowing 18% versus 2%, p = 0.008; osteophytes 21% versus 4%, p = 0.007), medial (joint space narrowing 33% versus 5%, p < 0.001) and anterior (osteophytes 15% versus 1%, p = 0.004) in the protrusio compared with the control group. After correction in hips with protrusio, progression of joint space narrowing (from 6% to 45%, p = 0.001) and osteophyte formation (from 15% to 52%, p = 0.002) was most pronounced laterally. CONCLUSIONS: At 10 years, in 51% of all hips undergoing open acetabular rim trimming for protrusio acetabuli, the hip can be preserved without further radiographic degeneration and a Merle d'Aubigne score > 15. Even with the lack of a control group with nonoperative treatment, isolated rim trimming may not entirely resolve the pathomorphology in protrusio hips given the clearly inferior results compared with surgical hip dislocation for FAI without severe overcoverage. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 27278678 TI - Your Best Life: Kindness is Its Own Reward. PMID- 27278679 TI - Cementless Total Hip Arthroplasty With Metasul Bearings Provides Good Results in Active Young Patients: A Concise Followup. AB - BACKGROUND: A primary concern of younger, more active patients who have undergone total hip arthroplasty (THA) is the longevity of the implant. Cementless fixation and hard-on-hard bearings are recognized as options to enhance THA durability. Earlier, we published a series of 83 cementless primary THAs using 28-mm metal-on metal (MoM) bearings in patients aged 50 years or younger; here we provide concise followup on that same group after an additional 8-year survey period. QUESTIONS/PURPOSES: (1) What is the long-term survivorship of cementless primary THA using 28-mm MoM bearings in patients aged 50 years or younger? (2) What are the clinical and radiographic results of cementless THA in this active patient population? (3) Can any of the observed implant failures or adverse events be attributed to the metallic nature of the bearing couple? METHODS: We retrospectively reviewed 83 cementless THAs performed in three institutions over a decade (1995-2004) in 68 patients with 28-mm MoM articulation. All patients (15 bilateral) had a median age of 42 years (range, 24-50 years) at the time of the index procedure and 56 of them (82% [70 hips]) had activity level graded Devane 4 or 5 before significant hip pain. A 28-mm MetasulTM articulation was used with an Alloclassic-SLTM cementless stem in all cases paired with three different cementless titanium acetabular components (one threaded and two press-fit cups) from the same manufacturer. Survivorship analysis was calculated according to Dobbs life table, patient clinical results were evaluated with use of the Postel Merle d'Aubigne scoring system, radiographic analysis was performed by independent observers, and cobalt level was determined in whole blood. RESULTS: The 15-year survivorship (33 hips at risk) for revision for any reasons (four hips) and for aseptic loosening (one hip) was 96% (95% confidence interval [CI], 81%-99%) and 99% (95% CI, 85%-99.9%), respectively. The median Merle d'Aubigne Postel score remained stable at 17 points (range, 10-18). Thus far, we have not observed pseudotumors or other adverse reactions to metallic debris. Eight hips have undergone reoperation: trochanteric suture removal (one), psoas tendon impingement (two), and five revisions for periprosthetic fracture (one), late infection (two), acetabular osteolysis (one, as a result of polyethylene backside wear), and one hydroxyapatite-coated cup for aseptic loosening. None of the complications, failures, or revisions observed so far could directly be related to the metallic nature of the 28-mm Metasul bearings used in this selected group of patients. CONCLUSIONS: The current survey at 13-year median followup has not yet indicated any long-term deleterious effects related to dissemination of metallic ions. Two senior authors continue to use 28- or 32-mm MetasulTM bearings with cementless THA components in young and active patient populations. Longer followup with a more sophisticated imaging study is necessary to confirm this so far positive report. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 27278680 TI - Anticancer activity and computational modeling of ternary copper (II) complexes with 3-indolecarboxylic acid and 1,10-phenanthroline. AB - Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit cancer-special proteasome and induce cell death in human cancer cells. However, the involved molecular mechanism is not known yet. We therefore synthesized three copper complexes and investigated their abilities on inhibiting proteasome activity and inducting apoptosis in human breast cancer cells. Furthermore, we employed molecular dockings to analyze the possible interaction between the synthetic copper complexes and the beta5 subunit of proteasome which only reflects the chymotrypsin-like activity. Our results demonstrate that three Cu(II) complexes possess potent proteasome inhibition capability in a dose dependent and time-dependent manner in MDA-MB-231 human breast cancer cells. They could bind to the beta5 subunit of the 20S proteasome, which consequently cause deactivation of the proteasome and tumor cell death. The present study is significant for providing important theoretical basis for design and synthesis of anticancer drugs with low toxicity, high efficiency and high selectivity. PMID- 27278682 TI - A 2-year dyadic longitudinal study of mothers' and fathers' marital adjustment when caring for a child with cancer. AB - OBJECTIVE: Studies examining interrelationships within parental couples confronted with pediatric cancer are scarce. This study explored dyadic longitudinal associations between both partners' family functioning and mood at diagnosis, and marital adjustment 2 years later. METHOD: Parents of children (n = 47 couples) with acute lymphoblastic leukemia (ALL) completed the Family Well Being Assessment and Profile of Mood States-Bipolar Form at diagnosis, and the Locke-Wallace Marital Adjustment Test 2 years post diagnosis. Multilevel linear models using the actor-partner interdependence model (APIM) and controlling for baseline marital adjustment were conducted to evaluate within subject and dyadic longitudinal effects. RESULTS: For mothers, better marital adjustment 2 years post diagnosis was associated with perception of greater family support and less role conflict and role overload at diagnosis. For fathers, better marital adjustment 2 years post-diagnosis was associated with perception of less role conflict, greater role ambiguity, and being more tired at diagnosis, as well as their partner's perception of less role conflict at diagnosis. CONCLUSIONS: These findings highlight the importance of considering both partners' perspectives in understanding marital adjustment across treatment phases in parents of children with ALL. Early interventions for couples should be tailored to meet each partner's needs in order to foster resilience within the couple. PMID- 27278681 TI - Opioid and cannabinoid synergy in a mouse neuropathic pain model. AB - BACKGROUND AND PURPOSE: Clinical studies have reported that pan-cannabinoid receptor agonists may have efficacy in neuropathic pain states and that this might be enhanced by co-administration with opioids. While cannabinoid-opioid analgesic synergy has been demonstrated in animal models of acute pain, it has not been examined in neuropathic pain models. We examined the effect of combination treatment with cannabinoid and opioid receptor agonists on allodynia and side effects in a nerve injury-induced neuropathic pain model. EXPERIMENTAL APPROACH: C57BL/6 mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. The effects of systemic administration of morphine and the pan cannabinoid receptor agonist, WIN55212, on allodynia and side effects were examined at 7-10 days post-CCI surgery. Isobolographic analysis was used to determine whether the effects of the combination were synergistic. KEY RESULTS: The opioid agonist morphine reduced CCI-induced mechanical and cold allodynia and produced motor incoordination, in a dose-dependent manner. WIN55212 reduced CCI induced allodynia and produced motor incoordination, catalepsy and sedation, in a dose-dependent manner, as we have observed previously. When administered together, WIN55212 and morphine reduced allodynia in a synergistic manner but had only an additive effect on motor incoordination. CONCLUSIONS AND IMPLICATIONS: These findings indicate that administration of a combination of a non-selective opioid and cannabinoid receptor agonist synergistically reduces nerve injury induced allodynia, while producing side effects in an additive manner. This suggests that this combination treatment has an improved anti-allodynic potency and therapeutic index in a neuropathic pain model. PMID- 27278683 TI - Interaction of Citrus Juices with Cyclosporine: Systematic Review and Meta Analysis. AB - INTRODUCTION: Cyclosporine is an immunosuppressant with narrow therapeutic window, metabolized mainly by cytochrome P450 3A4 (CYP3A4) and minimally by cytochrome P450 3A5 (CYP3A5). Citrus juices such as grapefruit juice (GFJ), orange, lemon, pomelo and lime were known to interact with cyclosporine in several randomized controlled trials. The present review is a systematic compilation and quantitative synthesis on the changes of cyclosporine pharmacokinetics with concomitant citrus juice administration. METHODS: Electronic databases were searched for randomized controlled trials evaluating the effect of any citrus juice on the pharmacokinetics of cyclosporine comparing with water or placebo in healthy volunteers using appropriate search strategies. Percent mean difference with standard error was used to assess the magnitude of difference in the following outcome measures: area under curve from time of drug administration to 24 h (AUC0-24), area under curve from time of drug administration to infinity (AUC0-infinity), maximum concentration (C max), time to achieve C max (T max), elimination half-life (T 1/2), clearance (CL), volume of distribution and frequency for adverse drug reactions following administration of cyclosporine. RevMan 5.3 software was used to assess heterogeneity (by I2 statistics), use random-effects model and generate pooled results and Forest plot. RESULTS: A total of 57 studies were obtained with the search strategy, of which seven were found eligible to be included in the present review. The pooled percent mean difference [95 % CI] for GFJ in comparison to controls for AUC0-24, AUC0-infinity, C max and T max of cyclosporine was observed to be 53 [43, 64], 53 [45, 62], 24 [12, 36] and 19 [12, 26], respectively. Similarly, pomelo juice was found to significantly increase both AUC0-infinity and C max with the pooled percent mean difference [95 % CI] as 23 [13, 32] and 25 [1, 50], respectively but decrease T 1/2 {-8 [-15, -1]} of cyclosporine. Orange juice did not alter any of the pharmacokinetic parameter of cyclosporine significantly. CONCLUSION: Citrus juices especially GFJ and pomelo juice were found to significantly increase the plasma exposure of cyclosporine while orange juice did not exhibit any significant interaction with cyclosporine. PMID- 27278684 TI - MicroRNA-17 induces epithelial-mesenchymal transition consistent with the cancer stem cell phenotype by regulating CYP7B1 expression in colon cancer. AB - MicroRNA-17 (miRNA-17/miR-17) expression has been confirmed to be significantly higher in colorectal cancer tissues than in normal tissues. However, its exact role in colorectal cancer has not yet been fully elucidated. In this study, we found that miR-17 not only promoted epithelial-mesenchymal transition (EMT), but also promoted the formation of a stem cell-like population in colon cancer DLD1 cells. We also wished to determine the role of cytochrome P450, family 7, subfamily B, polypeptide 1 (CYP7B1) in CRC. miR-17 was overexpressed using a recombinant plasmid and CYP7B1 was silenced by transfection with shRNA. Western blot analysis was used to determine protein expression in the DLD1 cells and in tumor tissues obtained from patients with colon cancer. Our results revealed that miR-17 overexpression led to the degradation of CYP7B1 mRNA expression in DLD1 cells. In addition, we found that the silencing of CYB7B1 promoted EMT and the formation of a stem cell-like population in the cells. Thus, our findings demonstrate that miR-17 induces EMT consistent with the cancer stem cell phenotype by regulating CYP7B1 expression in colon cancer. PMID- 27278685 TI - Validity of the Original and Short Versions of the Dynamic Gait Index in Predicting Falls in Stroke Survivors. AB - PURPOSE: This study aimed to investigate the validity of the original version and short version of the Dynamic Gait Index (DGI-8 and DGI-4) in predicting falls in stroke survivors. DESIGN: This is a retrospective, cross-sectional study. METHOD: This study collected data for 57 chronic stroke survivors and evaluated the validity of the DGI-8 and DGI-4. To test functional ability, the Sit-to-Stand Test, gait subscale of the Performance-Oriented Mobility Assessment, the 10-m Walk Test, the Fugl-Meyer assessment, and the Trunk Impairment Scale were used. FINDINGS: For the DGI-8, the cutoff value for the prediction of a fall was shown to be 16.5, with an area under the curve (AUC) of 0.78. The cutoff value of the DGI-4 was shown to be 9.5, with an AUC of 0.77. CONCLUSIONS: The study results show that the DGI-8 and DGI-4 have discrimination in the prediction of fall in stroke survivors. CLINICAL RELEVANCE: DGI-8 and DGI-4 can be useful for predicting falls of stroke patients, allowing better quality of care. PMID- 27278686 TI - Biomarker discovery using dry-lab technologies and high-throughput screening. PMID- 27278687 TI - The structure of slip-pulses and supershear ruptures driving slip in bimaterial friction. AB - The most general frictional motion in nature involves bimaterial interfaces, when contacting bodies possess different elastic properties. Frictional motion occurs when the contacts composing the interface separating these bodies detach via propagating rupture fronts. Coupling between slip and normal stress variations is unique to bimaterial interfaces. Here we use high speed simultaneous measurements of slip velocities, real contact area and stresses to explicitly reveal this bimaterial coupling and its role in determining different classes of rupture modes and their structures. We directly observe slip-pulses, highly localized slip accompanied by large local reduction of the normal stress near the rupture tip. These pulses propagate in the direction of motion of the softer material at a selected (maximal) velocity and continuously evolve while propagating. In the opposite direction bimaterial coupling favors crack-like 'supershear' fronts. The robustness of these structures shows the importance of bimaterial coupling to frictional motion and modes of frictional dissipation. PMID- 27278689 TI - Essential priorities of a good journal. PMID- 27278688 TI - Tree aboveground carbon storage correlates with environmental gradients and functional diversity in a tropical forest. AB - Tropical forests play a disproportionately important role in the global carbon (C) cycle, but it remains unclear how local environments and functional diversity regulate tree aboveground C storage. We examined how three components (environments, functional dominance and diversity) affected C storage in Dinghushan 20-ha plot in China. There was large fine-scale variation in C storage. The three components significantly contributed to regulate C storage, but dominance and diversity of traits were associated with C storage in different directions. Structural equation models (SEMs) of dominance and diversity explained 34% and 32% of variation in C storage. Environments explained 26-44% of variation in dominance and diversity. Similar proportions of variation in C storage were explained by dominance and diversity in regression models, they were improved after adding environments. Diversity of maximum diameter was the best predictor of C storage. Complementarity and selection effects contributed to C storage simultaneously, and had similar importance. The SEMs disengaged the complex relationships among the three components and C storage, and established a framework to show the direct and indirect effects (via dominance and diversity) of local environments on C storage. We concluded that local environments are important for regulating functional diversity and C storage. PMID- 27278690 TI - Autoimmune pancreatitis: with special reference to a localized variant. AB - In 2006, the Japan Pancreas Society revised the diagnostic criteria for autoimmune pancreatitis (AIP) so as to more clearly define its morphological, pathological, and immunological features, as follows: (1) diffuse or segmental narrowing of the main pancreatic duct with an irregular wall and diffuse or localized enlargement of the pancreas recognized by imaging studies; (2) high serum gamma globulin, IgG, or IgG4 levels, or the presence of autoantibodies; and (3) marked interlobular fibrosis and prominent infiltration of lymphocytes and plasma cells in the periductal area, occasionally with lymphoid follicles in the pancreas. Establishing a diagnosis of AIP has become easier with knowledge of its immunological abnormalities, including serum IgG4 levels. However, the localized form of AIP sometimes mimics pancreatic cancer. The rate of focal mass formation in patients with AIP is reportedly 24%-43%; however, there have been few reports on the histological findings of localized AIP, in contrast to mass-forming pancreatitis (MFP). Our review of patients who had undergone resection due to a preoperative diagnosis of MFP with possible cancer revealed 72% to be patients with localized AIP. For the discrimination of these conditions, it is important to recognize the characteristic ultrasonographic findings of AIP, i.e., (1) diffuse or localized enlargement and hypoechogenicity of the pancreas; (2) rarity of calcification, cystic lesions, and peripancreatic fluid collection; (3) thickened layer structure of the bile duct wall; (4) iso/hypervascularity in the swollen portion of the pancreas; (5) attenuation of pancreatic swelling and bile duct wall thickening after steroid therapy; and (6) multiple hypoechoic masses in various organs, including the pancreas. Contrast-enhanced endoscopic ultrasonography is potentially a useful tool in the differential diagnosis and for assessment of the efficacy of steroid therapy by enabling evaluation of the vascularity of the lesions. Along with the presence of IgG4-positive plasma cells, verification of obliterative phlebitis is highly specific for the histological diagnosis of AIP. PMID- 27278691 TI - Ultrasound follow-up of infantile hypertrophic pyloric stenosis (IHPS) during conservative therapy: ultrasound findings as criteria for diagnosis and cure. AB - PURPOSE: During conservative therapy of infantile hypertrophic pyloric stenosis (IHPS) with atropine sulfate, there are many patients who do not achieve normal values of pyloric wall thickness and canal length even though they are clinically cured (vomiting has ceased); an objective criterion for cure has not yet been established. The aim of this study was to examine whether the appearance of pyloric wall stratification can be used as a criterion for cure. METHODS: Twenty infants with IHPS who were treated conservatively were enrolled. Two of them ultimately required surgery. Ultrasound examinations were done serially and the pyloric wall thickness and canal length were measured. The echogenicity of the pyloric wall and the presence of wall stratification were noted. RESULTS: On admission, all infants satisfied the ultrasound criteria for IHPS and had a heterogeneous pyloric wall without stratification. With conservative therapy, symptoms disappeared, the pyloric wall thickness and the canal length gradually decreased, the echogenicity gradually became homogeneous and hypoechoic, and wall stratification appeared (in most cases before the pyloric wall thickness and the canal length had normalized). The absence of wall stratification suggests that cellular interstitial changes, such as edema or inflammation, are present in the pyloric wall in the acute stage. CONCLUSION: Pyloric wall stratification was absent during the acute stage, but it appeared after initiation of treatment but before the pyloric wall thickness and the canal length had normalized. The presence of pyloric wall stratification can be used as a criterion for cure; the absence of wall stratification can be added to ultrasound diagnostic criteria for IHPS. PMID- 27278692 TI - Analysis of the intensity of radio-frequency signals in intracranial ultrasonography of preterm infants. AB - PURPOSE: The purpose of this study was to evaluate the usefulness of analysis of the intensity of radio-frequency (RF) signals in intracranial ultrasonography of preterm infants. METHODS: Twenty neonatal infants admitted to the neonatal intensive care unit of our hospital were included in this study. Their gestational age was 33-35 weeks. The studies were performed with a System 5 ultrasound system with 3.0-and 5.0-MHz transducers. The transducer was placed on the anterior fontanel to obtain images. Regions of interest were determined based on B-mode images and were positioned at the thalamus, caudate nucleus, cerebral white matter, cerebellum, brain stem, and lateral ventricle. The software used for analysis of the RF signals was EchoMAT (Vingmed Ultrasound). RESULTS: The RF signals of the ventricle and the choroid plexus showed the lowest and the highest intensities, respectively. The intensities of the brain stem and vermis signals were the same, and were higher than the intensity of the cerebellar hemisphere. The thalamus and caudate nucleus showed macroscopically identical brightness levels; however, the intensity of the thalamus was lower than that of the caudate nucleus. The intensity of subependymal hemorrhage was lower than that of the caudothalamic groove. The intensity of subependymal cyst was the same as that of the lateral ventricle. The RF signal frequencies and intensities were distinctive in each tissue. CONCLUSION: The results of this study suggest that measurement of RF signal intensity may be useful to differentiate macroscopically similar lesions. PMID- 27278693 TI - Differential diagnosis of breast mass image-forming lesions based on changes in depth-width ratio and internal echo intensity by hand-held probe compression. AB - PURPOSE: Regarding mass image-forming lesions, the 2005 Guidelines for Ultrasonic Diagnosis of Breast Diseases, published by the Japan Society of Ultrasonics in Medicine (JSUM), includes the evaluation of tumor compressibility, which is visually assessed by the degree of deformation caused by applying external pressure to the tumor. However, this is only a subjective estimation under real time observation; consequently, quantitative evaluation of tumor deformation and the percentage change in internal echo intensity was attempted based on changes in the depth-width ratio and in the internal echo intensity on hand-held probe compression. We evaluated the usefulness of these measurements in the differential diagnosis of benign and malignant tumors. METHODS: The subjects were 139 patients (89 benign and 50 malignant cases) who underwent breast ultrasonography with a 10-MHz (from 4-to 10-MHz) linear probe. The deformation index (D.I.) of the tumor was defined as: [1 - (depth-width ratio with 3.0 +/- 0.6-kg-weighted compression)/(depth-width ratio without compression)] * 100 (%). The rate of change in internal echo intensity was defined as the echo intensity with compression divided by the echo intensity without compression * 100 (%). RESULTS: There was a significant difference in the D.I. between benign lesions (35.5% +/- 14.7%) and malignant lesions (15.4% +/- 6.2%) (P < 0.001). The cut-off ratio in differentiating benign from malignant lesions was approximately 25%. The rate of change in echo intensity of benign lesions (149.7% +/- 34.3%) was significantly higher than that of malignant lesions (122.9% +/- 19.9%) (P < 0.001). CONCLUSION: Using an electronic linear probe, quantitative indexes including the D.I. and the rate of change in internal echo intensity could be obtained with the help of a weight meter, and could prove effective for the differential diagnosis of breast mass-image forming lesions. PMID- 27278694 TI - Antenatal screening for circumvallate placenta. AB - PURPOSE: Prenatal recognition of circumvallate placenta is important because the condition may lead to some serious perinatal complications. METHODS: The possibility of antenatal ultrasonographic screening for circumvallate placenta was examined by measuring the thickness of the placenta at the thickest point. The study group consisted of 722 unselected patients with uncomplicated singleton pregnancies seen for routine ultrasonographic examination between 18 and 21 weeks' gestation. Data were collected from 11 deliveries complicated by completely circumvallate placenta and from 711 unaffected controls. RESULTS: The average thickness of the placenta was 2.22 +/- 0.36 cm in the control subjects, whereas it was 2.74 +/- 0.53 cm (P = 0.01 versus control) for circumvallate placentas. When a placental thickness greater than 3.0 cm was demonstrated, 19.4% (6/31) had a circumvallate placenta at delivery (P < 0.01). CONCLUSION: The current results suggest that measurement of placental thickness is useful for screening for circumvallate placenta. PMID- 27278695 TI - Gastrointestinal stromal tumor with a marked rotation. PMID- 27278696 TI - Portal gas in a patient with alcoholic liver cirrhosis. PMID- 27278697 TI - The spell of ventricular systolic function. PMID- 27278698 TI - The stiffness parameter beta assessed by an ultrasonic phase-locked echo-tracking system is associated with plaque formation in the common carotid artery. AB - PURPOSE: Assessment of plaque formation in the common carotid artery (CCA) is important for stratification of the risk of subsequent stroke. The stiffness parameter beta, which can be assessed using an ultrasonic phase-locked echo tracking system, was developed to evaluate arterial stiffness. The purpose this study was to examine the relationship of the stiffness parameter beta to intima media thickness (IMT) and plaque formation. METHODS: The stiffness parameter beta and mean IMT were measured using an ultrasonic phase-locked echo-tracking system and an automatic IMT measurement system, respectively, and the presence of plaque was assessed by ultrasonography in 347 subjects who took part in a health check up program for community-dwelling people in Hokkaido. RESULTS: Values of the stiffness parameter beta were significantly higher in subjects with plaque formation than in those without plaque (10.60 +/- 0.45 vs. 8.88 +/- 0.23, P < 0.005) in whom IMT was not thickened; however, it was not different in subjects with increased IMT (>1.0 mm). The percentage of plaque formation was significantly correlated with the value of the stiffness parameter beta. Furthermore, the stiffness parameter beta was significantly correlated with plaque formation after adjustment for several clinical variables (odds ratio 1.113-1.178, P < 0.001). CONCLUSION: The stiffness parameter beta is associated with plaque formation in the CCA, especially in subjects with a normal IMT. This could potentially be used as a predictor for plaque formation. PMID- 27278699 TI - Evaluation of procedures for decontaminating ultrasound probes. AB - PURPOSE: To determine suitable procedures for decontaminating ultrasound probes. METHODS: We investigated bacterial transmission via ultrasound probes that were not wiped, wiped with a plain paper towel, or wiped with an ethanol-soaked paper towel. RESULTS: The unwiped probes transmitted large numbers of bacteria, which were markedly reduced by wiping the probes with a plain paper towel, and almost completely eliminated by wiping with an ethanol-soaked paper towel. CONCLUSION: Improperly decontaminated ultrasound probes can transmit bacteria among patients. Ultrasound probes should be decontaminated by wiping with a paper towel after examinations to prevent bacterial transmission. Plain or ethanol-soaked paper towels should be used depending on the situation. PMID- 27278700 TI - Quantification of tumor vascularity with contrast-enhanced ultrasound for early response of transcatheter arterial chemoembolization for hepatocellular carcinoma: a report of three cases. AB - Many contrast-enhanced ultrasound (CE-US) studies have been conducted by qualitative analysis of blood flow, such as classification of enhancement pattern. We evaluated early response of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) by quantitative analysis of intratumoral vascularity with CE-US in three patients. Three patients (one man, two women) with HCCs were treated in July 2009. CE-US with perfluorocarbon microbubbles (Sonazoid) and CT were performed serially before and 5 days after TACE. Post-processing enhancement intensity on US was analyzed to determine mean transit time (s), time to peak (s), enhancement peak intensity (dB), and "A" (scaling factor) by ultrasound quantification software after the data were fitted to a gamma variate curve. Mean transit time was prolonged by TACE in all three patients. Mean transit time rates on CE-US were 64.3, 33.8, and 65.6%, respectively, whereas the avascular rates on CT were 59.07, 31.71, and 62.25%, respectively. Mean transit time rates on CE-US approximated avascular rates on CT. Mean transit time rate may quantitatively indicate the early response of HCC to TACE. PMID- 27278701 TI - A rare case of coiling of the brachial artery: a description of the sonographic features. AB - We report the case of a patient with 360 degrees coiling of the brachial artery that had been previously misdiagnosed as aneurysms of the right brachial artery on sonography performed at another institution. The previous misdiagnosis occurred due to sonographic pitfalls in gray-scale and color imaging, which led the operator to make a false interpretation. Knowledge of Doppler analysis and sonographic interpretation of arterial coiling may improve the diagnostic accuracy for this condition. PMID- 27278702 TI - Congenitally corrected transposition of the great arteries. AB - Congenitally corrected transposition of the great arteries (cTGA) is an uncommon cardiac malformation characterized by discordant atrioventricular and ventriculoarterial connections. Most cases of cTGA are associated with cardiac anomalies. As the ventricular outflow tract may appear to arise correctly from the right and left ventricles, cases of cTGA with a mild associated anomaly are rarely detected prenatally. Parallel vessels are evident in cTGA, but this sign is also present in complete TGA. We report a case of cTGA diagnosed in utero at 29 weeks' gestation. The fetus was diagnosed as TGA and referred to our hospital at 28 weeks' gestation. cTGA was found at 29 weeks' gestation in our hospital, and no additional cardiac anomalies were seen prenatally. After birth, patent ductus arteriosus with bidirectional flow was present. Careful examination of the four-chamber view suggested atrioventricular discordance. Identification of a parallel course of the great vessels, with the aorta anterior and to the left of the pulmonary trunk (l-transposition), may help accurate prenatal diagnosis of cTGA. PMID- 27278703 TI - Sonographic findings of Sister Mary Joseph's nodule from ovarian cancer. AB - Sister Mary Joseph's nodule (SMJN), which is known as a malignant tumor metastasized to the umbilicus, is a rare condition. We report ultrasonic findings of SMJN secondary to ovarian cancer in a 66-year-old woman. The umbilical tumor was observed as a hypoechoic mass with punctate hyperechoic foci. A pathological specimen obtained by needle biopsy confirmed adenocarcinoma with psammoma bodies. A comparison of the ultrasonographic findings with the pathological findings of the resected specimen suggested that the hyperechoic foci corresponded to psammoma bodies. When hyperechoic foci are observed inside SMJN by ultrasonography, adenocarcinoma from ovarian cancer should be included in the differential diagnosis. PMID- 27278704 TI - Measurement of left atrial appendage size by transesophageal echocardiography. AB - Transesophageal echocardiography (TEE) is the most common imaging method for evaluating left atrial morphology. Recent advances in 64-slice multidetector computed tomography (64-MDCT) allow accurate measurement of left atrial appendage (LAA) volume. The aim of this study was to evaluate the accuracy of LAA sizing by TEE in comparison with 64-MDCT in patients with atrial fibrillation. Electrocardiogram-gated 64-MDCT and TEE were performed within 2 days in 18 consecutive patients (63 +/- 9 years old, 12 males, 5 paroxysmal atrial fibrillation) with nonvalvular atrial fibrillation. LAA area and LAA volume were measured at end-systole by TEE and 64-MDCT, respectively. The largest LAA area was measured on TEE image. Five patients were in sinus rhythm during examinations. In all patients, LAA was clearly visualized; the largest area of LAA was 9.3 +/- 3.9 mm(2) and the LAA volume was 21.6 +/- 7.5 ml. A significant correlation between LAA area and LAA volume was observed (p = 0.0003, r = 0.75). TEE allows a detailed evaluation of the LAA structure by two-dimensional imaging. LAA size could be evaluated by TEE despite its morphological complexity, i.e., sac-like or multilobed structure. PMID- 27278705 TI - Processed skin surface images acquired by acoustic impedance difference imaging using the ultrasonic interference method: a pilot study. AB - To clarify the potential of a novel system using the acoustic impedance difference imaging (AIDI) method for diagnosis of skin disorders, we used it on a coin and swine skin. An ultrasound wave with a central frequency of 20 MHz, emitted from a fused quartz rod with a diameter of 1.25 mm, was focused on the surface of the coin and skin samples. The difference in acoustic impedance was determined by the reflection-type interference-based acoustic impedance measurement method. The processed data were produced as greyscale images on which the maximum measured amplitudes were mapped. We applied the method to a coin. Swine skin, burned and covered with an acrylic sheet with a thickness of 0.2 mm (a few times the half-wavelength) to eliminate the undulations of the skin surface, was employed to obtain processed images from which undulation data were excluded. All the processed images obtained corresponded almost exactly with the magnified optical ones. In the processed images of swine skin, a marked difference was found after the burning procedure. The processed images obtained using the AIDI method reflected not only the undulations but also other information such as elasticity. In conclusion, our system using AIDI has the potential to become a useful modality for the diagnosis of skin disorders. PMID- 27278706 TI - Antenatal three-dimensional sonographic features of placental shelf. PMID- 27278707 TI - Inter-twin contact in a case of monochorionic diamniotic twins with acrania of one twin fetus at 10-13 weeks' gestation. PMID- 27278708 TI - Ultrasound diagnostic criteria for thyroid nodule. PMID- 27278709 TI - Elevated levels of chemerin, leptin, and interleukin-18 in gestational diabetes mellitus. AB - OBJECTIVE: We aimed to assess the levels of adipokine and their relation to gestational diabetic related clinical phenotypes and fetal growth parameters. MATERIAL AND METHODS: International Association of the Diabetes and Pregnancy Study criteria was used to classify gestational diabetic cases (n = 208) and euglycemic controls (n = 300). ELISA assays were performed for insulin, chemerin, leptin, and interleukin-18 (IL-18). Mann-Whitney U test, Chi-square/Fisher exact test, multiple regression analyses, and ROC curves were applied with significant p values of <0.05. RESULTS: Levels of chemerin, IL-18, and leptin were seven-, four-, and five-folds higher in cases versus controls, respectively (p < 0.01). The adipokine showed strong positive correlation with fasting blood glucose, homeostasis model assessment of insulin resistance, and fetal weight (p < 0.01). Odds of GDM association remained significant for chemerin (OR 1.522; 1.097-2.110) and leptin (OR 2.579; 1.503-4.425) while all associations were lost for IL-18 (p > 0.05) after multiple adjustments. Raised chemerin levels were identified in 96% cases (n = 201) employing the proposed cut off value >15.49 ng/ml. CONCLUSION: High chemerin and leptin levels are seen in GDM which may be associated with subclinical inflammation suggesting a role in development of insulin resistance. PMID- 27278710 TI - Host and ecology both play a role in shaping distribution of digenean parasites of New Zealand whelks (Gastropoda: Buccinidae: Cominella). AB - Digenean parasites infecting four Cominella whelk species (C. glandiformis, C. adspersa, C. maculosa and C. virgata), which inhabit New Zealand's intertidal zone, were analysed using molecular techniques. Mitochondrial 16S and cytochrome oxidase 1 (COI) and nuclear rDNA ITS1 sequences were used to infer phylogenetic relationships amongst digenea. Host species were parasitized by a diverse range of digenea (Platyhelminthes, Trematoda), representing seven families: Echinostomatidae, Opecoelidae, Microphallidae, Strigeidae and three, as yet, undetermined families A, B and C. Each parasite family infected between one and three host whelk species, and infection levels were typically low (average infection rates ranged from 1.4 to 3.6%). Host specificity ranged from highly species-specific amongst the echinostomes, which were only ever observed infecting C. glandiformis, to the more generalist opecoelids and strigeids, which were capable of infecting three out of four of the Cominella species analysed. Digeneans displayed a highly variable geographic range; for example, echinostomes had a large geographic range stretching the length of New Zealand, from Northland to Otago, whereas Family B parasites were restricted to fairly small areas of the North Island. Our results add to a growing body of research identifying wide ranges in both host specificity and geographic range amongst intertidal, multi host parasite systems. PMID- 27278711 TI - Novel p-wave superfluids of fermionic polar molecules. AB - Recently suggested subwavelength lattices offer remarkable prospects for the observation of novel superfluids of fermionic polar molecules. It becomes realistic to obtain a topological p-wave superfluid of microwave-dressed polar molecules in 2D lattices at temperatures of the order of tens of nanokelvins, which is promising for topologically protected quantum information processing. Another foreseen novel phase is an interlayer p-wave superfluid of polar molecules in a bilayer geometry. PMID- 27278712 TI - Pharmacokinetic and Pharmacodynamic Evaluation of the Drug-Drug Interaction Between Isavuconazole and Warfarin in Healthy Subjects. AB - This phase 1 trial evaluated pharmacokinetic and pharmacodynamic interactions between the novel triazole antifungal agent isavuconazole and warfarin in healthy adults. Multiple doses of isavuconazole were administered as the oral prodrug, isavuconazonium sulfate (372 mg 3 times a day for 2 days loading dose, then 372 mg once daily thereafter; equivalent to isavuconazole 200 mg), in the presence and absence of single doses of oral warfarin sodium 20 mg. Coadministration with isavuconazole increased the mean area under the plasma concentration-time curves from time 0 to infinity of S- and R-warfarin by 11% and 20%, respectively, but decreased the mean maximum plasma concentrations of S- and R-warfarin by 12% and 7%, respectively, relative to warfarin alone. Mean area under the international normalized ratio curve and maximum international normalized ratio were 4% lower in the presence vs absence of isavuconazole. Mean warfarin area under the prothrombin time curve and maximum prothrombin time were 3% lower in the presence vs absence of isavuconazole. There were no serious treatment-emergent adverse events (TEAEs), and no subjects discontinued the study due to TEAEs. All TEAEs were mild in intensity. These findings indicate that coadministration with isavuconazole has no clinically relevant effects on warfarin pharmacokinetics or pharmacodynamics. PMID- 27278713 TI - Multiple functions of volatiles in flowers and leaves of Elsholtzia rugulosa (Lamiaceae) from southwestern China. AB - Although the roles of volatile compounds have been examined separately in plant herbivore or plant-pollinator interactions, few studies have focused on how plant scents can attract effective pollinators, repel ineffective pollinators, and defend against attacks by insect herbivores. We explored the functional significance of volatile compounds that impart a strong odor to Elsholtzia rugulosa, a shrub species in southwestern China. We monitored the pollinating honey bee Apis cerana, as well as two occasional visitors - Vespa velutina and a Bombus sp. - and an herbivorous beetle Oxycetonia jocunda. Behavior experiments using Y-tubes showed that honey bees were attracted primarily by floral scent while hornets and bumble bees were repelled by both the flowers and leaves. Analysis via gas chromatography-mass spectrometry revealed that these tissue types differed in their compositions and relative amounts of volatile compounds. When the plants were damaged, the average relative amounts of Elsholtzia ketone rapidly increased in the flowers and leaves. Furthermore, herbivorous beetles were strongly repelled by damaged tissues, suggesting a potential defense signaling function by these compounds. Our findings again demonstrate that scents have multiple functions in the interactions among plants and insects. PMID- 27278715 TI - Disentangling functions of online aggression: The Cyber-Aggression Typology Questionnaire (CATQ). AB - Aggression in online contexts has received much attention over the last decade, yet there is a need for measures identifying the proximal psychological drivers of cyber-aggressive behavior. The purpose of this study was to present data on the newly developed Cyber-Aggression Typology Questionnaire (CATQ) designed to distinguish between four distinct types of cyber-aggression on dimensions of motivational valence and self-control. A sample 314 undergraduate students participated in the study. The results confirmed the predicted four-factor structure providing evidence for distinct and independent impulsive-aversive, controlled-aversive, impulsive-appetitive, and controlled-appetitive cyber aggression types. Further analyses with the Berlin Cyberbullying Questionnaire, Reactive Proactive Aggression Questionnaire, and the Behavior Inhibition and Activation Systems Scale provide support for convergent and divergent validity. Understanding the motivations facilitating cyber-aggressive behavior could aid researchers in the development of new prevention and intervention strategies that focus on individual differences in maladaptive proximal drivers of aggression. Aggr. Behav. 43:74-84, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27278714 TI - A Randomized Clinical Trial Evaluating the Effects of Oligosaccharides on Transfer of Passive Immunity in Neonatal Dairy Calves. AB - BACKGROUND: Bacterial contamination of colostrum is common and can decrease IgG absorption in neonatal calves. Strategies that mitigate this situation without complicating colostrum management will benefit dairy calf health and survival. OBJECTIVES: To evaluate the effects of supplementing colostrum with oligosaccharides (OS) on serum IgG concentration and apparent efficiency of absorption of IgG (AEA%) in calves fed unpasteurized colostrum and characterize these outcomes with respect to colostrum bacterial exposures. ANIMALS: One hundred twenty-three neonatal dairy calves. METHODS: Randomized, blinded, controlled clinical trial conducted at a commercial dairy operation. Calves were enrolled at birth in 1 of 4 treatment groups. Data were complete for 123 calves, which were distributed across the treatment groups as follows: mannan oligosaccharides (MOS), n = 33; Saccharomyces galacto-oligosaccharides (SGOS), n = 31; Bifidobacterium galacto-oligosaccharides (BGOS), n = 28; and lactose control (CON), n = 31. A commercial radial immunodiffusion kit was used to determine colostrum and serum IgG concentrations. Conventional microbiology methods were used to enumerate colostrum bacterial counts. RESULTS: Bacterial counts were not significantly different among treatment groups. Total bacterial plate counts (TPC) were relatively low for the majority of colostrum samples, but TPC had a significant negative effect on serum IgG concentration and AEA% in the lactose-supplemented control group but not the OS treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that a complement of OS structures may mitigate adverse effects of bacteria on transfer of passive immunity (TPI). PMID- 27278716 TI - The Use of NS1 Rapid Diagnostic Test and qRT-PCR to Complement IgM ELISA for Improved Dengue Diagnosis from Single Specimen. AB - Timely and accurate dengue diagnosis is important for differential diagnosis and immediate implementation of appropriate disease control measures. In this study, we compared the usefulness and applicability of NS1 RDT (NS1 Ag Strip) and qRT PCR tests in complementing the IgM ELISA for dengue diagnosis on single serum specimen (n = 375). The NS1 Ag Strip and qRT-PCR showed a fair concordance (kappa = 0.207, p = 0.001). While the NS1 Ag Strip showed higher positivity than qRT-PCR for acute (97.8% vs. 84.8%) and post-acute samples (94.8% vs. 71.8%) of primary infection, qRT-PCR showed higher positivity for acute (58.1% vs. 48.4%) and post acute (50.0% vs.41.4%) samples in secondary infection. IgM ELISA showed higher positivity in samples from secondary dengue (74.2-94.8%) than in those from primary dengue (21.7-64.1%). More primary dengue samples showed positive with combined NS1 Ag Strip/IgM ELISA (99.0% vs. 92.8%) whereas more secondary samples showed positive with combined qRT-PCR/IgM ELISA (99.4% vs. 96.2%). Combined NS1 Ag Strip/IgM ELISA is a suitable combination tests for timely and accurate dengue diagnosis on single serum specimen. If complemented with qRT-PCR, combined NS1 Ag Strip/IgM ELISA would improve detection of secondary dengue samples. PMID- 27278717 TI - Nursing in an imperfect world: Storytelling as preparation for mental health nursing practice. AB - Storytelling is a valuable adjunctive method of preparing undergraduate mental health nursing students for practice. To explore the possibilities of this method of teaching, 100 stories were collected from experienced nurses working in mental health and analysed using a case study methodology. The aim was to explore the purpose of clinical anecdotes told by experienced nurses working in mental health settings to undergraduates and new recruits, with an ancillary purpose of looking at the implications of these anecdotes for the exploration of contemporary mental health practice and education. A framework for student discussion of stories is provided. The insights gained illuminate not only the history of mental health nursing and the daily activities of nurses working in mental health, but also some of the deep-level skills developed and used by these nurses as they work in the complexity and ambiguity of an imperfect world where the job requires managing the unexpected every shift, and where there might not always be a textbook-perfect solution to clinical situations. PMID- 27278718 TI - Urinary cotinine levels of electronic cigarette (e-cigarette) users. AB - The popularity of electronic cigarettes (e-cigarettes) is rapidly increasing in many countries. These devices are designed to imitate regular cigarettes, delivering nicotine via inhalation without combusting tobacco but currently, there is a lack of scientific evidence on the presence or absence of nicotine exposure. Such research relies on evidence from e-cigarette users urine samples. In this study, we aimed to determine the levels and compare the amount of nicotine to which e-cigarette users, cigarette smokers and passive smokers are exposed. Therefore, urine samples were collected from e-cigarette users, cigarette smokers, passive smokers, and healthy nonsmokers. The urinary cotinine levels of the subjects were determined using gas chromatography-mass spectrometry. The mean (+/-SD) urinary cotinine levels were determined as 1755 +/ 1848 ng/g creatinine for 32 e-cigarette users, 1720 +/- 1335 ng/g creatinine for 33 cigarette smokers and 81.42 +/- 97.90 ng/g creatinine for 33 passive smokers. A significant difference has been found between cotinine levels of e-cigarette users and passive smokers (p < 0.05). There were no statistically significant differences between e-cigarette users and cigarette smokers (p > 0.05). This is a seminal study to demonstrate the e-cigarette users are exposed to nicotine as much as cigarette smokers. PMID- 27278719 TI - Primary health care for people with an intellectual disability: an exploration of demographic characteristics and reasons for encounters from the BEACH programme. AB - BACKGROUND: People with an intellectual disability (ID) have complex and different patterns of healthcare needs. Poor participation in primary health care contributes to the high levels of undetected and unmanaged health issues and premature deaths of people with an ID. Limited research is available on the characteristics of people with an ID, their reasons for consulting general practitioners (GPs), and if these differ to people without an ID. Gaining such insights may provide an avenue to better understand patterns of primary care use and potential gaps in usage by people with an ID given their complex health profile compared with people without an ID. METHOD: A secondary analysis of data collected January 2003 to December 2012 from The Bettering the Evaluation and Care of Health programme was used. Participant characteristics and their reasons for encounter, pre- and post-age-sex standardisation, at all GP encounters with people identified in the encounter record as having an ID ('ID' encounters, n = 690) were compared with those at 'non-ID' encounters (n = 970 641). Statistical significance was tested with chi-squared statistics or 95% confidence intervals as appropriate. RESULTS: This study identified significant differences in participant characteristics and their reasons for consulting GPs at ID encounters compared with non-ID encounters. Participants at ID encounters had a skewed demography, an over-representation of presentations for psychological, social and 'general and unspecified' reasons, and an under-representation of presentations for core physical health and preventive health measures. Administrative rather than medically related reasons dominated presentations to general practice at ID encounters. CONCLUSION: There are significant differences in the characteristics of participants and their reasons for presentation to general practice in Australia for participants at ID encounters compared with non-ID encounters. This work suggests that there is a difference in service use patterns between these two groups. These findings may suggest that people with an ID experience barriers to participating in essential primary healthcare services. PMID- 27278720 TI - Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo. AB - Emodin is an active ingredient derived from root and rhizome of Rheum palmatum L and many studies have reported that it exhibits anticancer effects in a number of human tumors. However, there is little information demonstrating the possible effects of emodin on the proliferation and apoptosis of hepatocellular carcinoma (HCC). In the present study, we show that emodin may inhibit the proliferation of SMMC-7721 cells in a dose- and time-dependent manner and induced apoptosis of cells in a concentration-dependent manner after treatment for 24 h. Moreover, we further discovered that the possible molecular mechanisms involved may relate to the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Emodin may induce the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38 while mildly suppressed the expression of p-c-Jun-N-terminal kinase (p-JNK). However, emodin did not affect the expression of the total (t)-ERK, t-p38 or t-JNK. Furthermore, emodin also suppressed the activation of p-AKT, but not the t-AKT. In vivo, we found that emodin suppressed tumor growth in experimental mice without an obvious change in body weight, which may work through the antiproliferation and apoptosis inducing effects. Moreover, emodin improves the liver and kidney function in mice, revealing that emodin may improve the life quality of the mice with implanted tumors. In conclusion, the above findings indicate that emodin may be a potentially effective and safe drug to induce apoptosis of HCC. PMID- 27278721 TI - Prognostic value of gray matter to white matter ratio in hypoxic and non-hypoxic cardiac arrest with non-cardiac etiology. AB - PURPOSE: This study evaluated the prognostic performance of the gray to white matter ratio (GWR) on brain computed tomography (CT) in out-of-hospital cardiac arrest (OHCA) survivors with a noncardiac etiology and compared the prognostic performance of GWR between hypoxic and nonhypoxic etiologies. METHODS: Using a multicenter retrospective registry of adult OHCA patients treated with targeted temperature management, we identified those with a noncardiac etiology who underwent brain CT within 24 hours after restoration of spontaneous circulation. Attenuation of the gray matter and white matter (at the level of the basal ganglia, centrum semiovale, and high convexity) were measured and GWRs were calculated. The primary outcome was neurologic outcome. RESULTS: Of 164 patients, 145 (88.4%) were discharged with a poor neurologic outcome. Lower GWR was associated with a poor neurologic outcome. The sensitivities of this marker were markedly low (9.7%-43.5%) at cutoff values, with 100% sensitivity. The cutoff values of the GWR for hypoxic arrest showed higher sensitivities than those for nonhypoxic arrest. The area under the curve (AUC) values of the GWR for the caudate nucleus/posterior limb of the internal capsule, putamen/corpus callosum, and basal ganglia were significant in the hypoxic group, whereas the AUC of the putamen/corpus callosum was the only significant GWR in the nonhypoxic group. CONCLUSION: A low GWR is associated with poor neurologic outcome in noncardiac etiology OHCA patients treated with targeted temperature management. Gray to white matter ratio can help to predict the neurologic outcome in a cardiac arrest with hypoxic etiology rather than a nonhypoxic etiology. PMID- 27278722 TI - Ultrasound-accelerated rheolytic thrombectomy for impending paradoxical embolism. PMID- 27278723 TI - Unexpected survival of sudden cardiac arrest patient with large multiple brain infarction after therapeutic hypothermia. PMID- 27278724 TI - Identification and characteristics of the testes-specific gene, Ccdc38, in mice. AB - Distinguishing the testes-specific genes in different species may disclose key genes associated with testes-specific functions and provide sufficient information for the study and treatment of male infertility. A testes-specific gene, coiled-coil domain containing 38 (Ccdc38), was identified by screening UniGene libraries. Systematic bioinformatics analysis demonstrated that the CCDC38 protein was conserved in various mammalian species. It was determined that CCDC38 was exclusively expressed in testes and its expression increased from 2-8 weeks of age. Additional immunohistochemical analysis indicated that CCDC38 was mainly expressed in spermatogonia and spermatocytes. It is of note that, immunofluorescence and co-immunoprecipitation assays demonstrated that CCDC38 interacted with ubiquitinated histone H2A in mouse testes. Therefore, these results suggest that Ccdc38 is a testes-specific gene, which may be important for mouse spermatogenesis. PMID- 27278725 TI - Anti-HIV-1 potency of the CRISPR/Cas9 system insufficient to fully inhibit viral replication. AB - The range of genome-editing tools has recently been expanded. In particular, an RNA-guided genome-editing tool, the clustered regularly interspaced short palindromic repeat (CRISPR)-associated 9 (Cas9) system, has many applications for human diseases. In this study, guide RNA (gRNA) to target gag, pol and a long terminal repeat of HIV-1 was designed and used to generate gRNA-expressing lentiviral vectors. An HIV-1-specific gRNA and Cas9 were stably dually transduced into a highly HIV-1-susceptible human T-cell line and the inhibitory ability of the anti-HIV-1 CRISPR/Cas9 lentiviral vector assessed. Although clear inhibition of the early phase of HIV-1 infection was observed, as evaluated by a VSV-G pseudotyped HIV-1 reporter system, the anti-HIV-1 potency in multiple rounds of wild type (WT) viral replication was insufficient, either because of generation of resistant viruses or overcoming of the activity of the WT virus. Thus, there are potential difficulties that must be addressed when considering anti-HIV-1 treatment with the CRISPR/Cas9 system alone. PMID- 27278736 TI - Resveratrol inhibits hyperglycemia-driven ROS-induced invasion and migration of pancreatic cancer cells via suppression of the ERK and p38 MAPK signaling pathways. AB - Increasing evidence suggests that there is a strong relationship between diabetes mellitus (DM) and pancreatic cancer. Our previous study revealed that hyperglycemia could enhance the invasive and migratory activities of pancreatic cancer cells. Resveratrol, a natural polyphenolic phytoalexin, has many biological and pharmaceutical properties, including antioxidant and anti tumorigenic capabilities. The aim of the present study was to evaluate whether resveratrol affects hyperglycemia-induced reactive oxygen species (ROS) production as well as the invasion and migration of pancreatic cancer and its underlying mechanisms. Human pancreatic cancer Panc-1 cells were exposed to high glucose condition with or without resveratrol, N-acetylcysteine (NAC, a scavenger of free radicals), PD 98059 (an ERK inhibitor) or SB 203580 (a p38 MAPK inhibitor). The intracellular ROS and hydrogen peroxide (H2O2) were determined using 2,7-dichlorodihydrofluorecein diacetate and H2O2 assay. MTT, wound healing assay and transwell matrigel invasion assay were used to detect the proliferation, migration and invasion potential of cancer cells. The expressions of uPA, E-cadherin and Glut-1 were examined using QT-PCR and western blot analysis at mRNA and protein levels. The activation of p-ERK, p-p38 and p-NF kappaB were measured by western blot analysis. The results of the present study showed that resveratrol could significantly decrease high glucose-induced production of ROS and H2O2 in Panc-1 cells. Resveratrol was also able to inhibit high glucose-induced proliferation, migration and invasion of pancreatic cancer cells. High glucose-modulated expression of uPA, E-cadherin and Glut-1 were inhibited by resveratrol. In addition, high glucose-induced activation of ERK and p38 MAPK signaling pathways as well as the transcription factor NF-kappaB could also be suppressed by resveratrol. Furthermore, resveratrol was able to suppress H2O2-induced migration and invasion abilities of pancreatic cancer cells. Taken together, these data indicate that resveratrol plays an important role in suppressing hyperglycemia-driven ROS-induced pancreatic cancer progression by inhibiting the ERK and p38 MAPK signaling pathways, providing evidence that resveratrol might be a potential candidate for chemoprevention of pancreatic cancer. PMID- 27278737 TI - CREBRF is a potent tumor suppressor of glioblastoma by blocking hypoxia-induced autophagy via the CREB3/ATG5 pathway. AB - Hypoxia induces protective autophagy in advanced glioblastoma cells, and targeting this process may improve the outcome for glioblastoma patients. Recent studies have suggested that the autophagic process is upregulated in glioblastoma cells in response to extensive hypoxia. Here, we describe a novel tumor suppressor in glioblastoma cells, whereby hypoxia downregulated CREBRF expression and acts as a potent inhibitor of autophagy in glioblastoma cells via the CREB3/ATG5 pathway. Our results demonstrate that CREBRF expression negatively correlates with autophagic and HIF-1alpha levels in different grade gliomas. Given that CREBRF is a negative regulator of CREB3, CREB3 knockdown also repressed hypoxia-induced autophagy in glioblastoma cells in vitro. Collectively, our findings provide new insight into the molecular mechanisms underlying hypoxia induced glioblastoma cell autophagy and indicate that the hypoxia/CREBRF/CREB3/ATG5 pathway plays a central role in malignant glioma progression. PMID- 27278738 TI - Oscillatory Mechanics in Asthma: Emphasis on Airway Variability and Heterogeneity. AB - Spirometry is one of the most widely used tests in the assessment and monitoring of asthma. However, spirometry cannot be performed in very young children and some adult patients, and is poorly sensitive to small airways, which are primarily involved in the pathophysiology of asthma. The forced oscillation technique (FOT) has emerged as a powerful alternative technique that instead characterizes respiratory mechanics during normal breathing with no forced maneuver. In this review we highlight the current state of the art of the FOT and its utility in the assessment of lung function in asthma. First we briefly discuss the clinical features and characteristics of asthma. This is followed by a discussion of the assessment of airway obstruction and airway hyperresponsiveness using spirometry. We then review the basics of FOT and its application in respiratory diseases. FOT data are particularly amenable to modeling as an aide to physiological interpretation, and we review several common approaches. This is followed by an in-depth discussion of the assessment of airway variability and heterogeneity using FOT in asthma. Finally, we speculate on the potential clinical utility of FOT in asthma. PMID- 27278740 TI - Magnetic Resonance of Brown Adipose Tissue: A Review of Current Techniques. AB - This article reviews recent efforts in magnetic resonance imaging (MRI) and spectroscopy (MRS) of brown adipose tissues (BAT). The article does not differentiate classical BAT from more recently introduced beige/ brite adipocytes, as the unequivocal detection of these hybrid adipocytes with MRI and MRS remains an unmet need and unsolved challenge. BAT studies in both animals and humans have progressed rapidly during the past decade, spanning a broad spectrum of researchers from basic science laboratories to clinical investigators in primary care hospitals. While positron emission and computed tomography (PET/CT) is likely to remain as a reference modality in BAT imaging in the near future, approaches using MRI and MRS have emerged as viable alternatives. The specific signal contrasts that allow an MR system to assess BAT morphology and function are emphasized. Methods that measure tissue fat content, blood flow and perfusion, water diffusion, temperature, and substrate metabolism are explained and pertinent literature reports that utilize these approaches are highlighted. Finally, this article provides an outlook on research opportunities and future directions. PMID- 27278741 TI - Review of Texture Quantification of CT Images for Classification of Lung Diseases. AB - Computer-based identification of abnormal regions and classification of diseases using CT images of the lung has been a goal of many investigators. In this paper, we review research that has used texture analysis along with segmentation and fractal analysis. First, a review of texture methods is performed. Recent research on quantitative analysis of the lung using texture methods is categorized into six groups of computational methods: structural, statistical, model based, transform domain, texture-segmentation, and texture-fractal analysis. Finally, the applications of texture-based methods combined with either segmentation algorithms or fractal analysis is evaluated on lung CT images from patients with diseases such as emphysema, COPD, and cancer. We also discuss applications of artificial neural networks, support vector machine, k-nearest, and Bayesian methods to classify normal and diseased segments of CT images of the lung. A combination of these texture methods followed by classifiers could lead to efficient and accurate diagnosis of pulmonary diseases such as pulmonary fibrosis, emphysema, and cancer. PMID- 27278739 TI - Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits. AB - Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration. PMID- 27278742 TI - Diffusion-Weighted Magnetic Resonance Imaging Attenuation Factors and Their Selection for Cancer Diagnosis and Monitoring. AB - Diffusion-weighted imaging (DWI) is based on the detection of water molecule movement in interstitial and intracellular space, and that motion may be restricted in ischemia and in tumors. An early diagnosis and characterization of several cancer related diseases is possible with DWI. Diffusion-weighted images are therefore important for patient management. Knowledge of the technical requirements for DWI, including a suitable selection of b-values for differentiating between perfusion and true diffusion, as well as an understanding of the advantages and limitations of different b-values selections, is necessary to obtain reliable diagnostic results. The aim of this article is to review the fundamentals of the DWI technique, the common protocols used, b-value selection, and DWI's main contribution to neoplasm detection and staging. PMID- 27278743 TI - Etiology and Biomechanics of Midfoot (Lisfranc) Injuries in Athletes. AB - Tarsometatarsal (TMT) dislocations are an uncommon but debilitating athletic injury. When symptomatic midfoot instability persists, an injured athlete frequently requires surgical stabilization and rehabilitation for up to 9 months before returning to full athletic participation. Unfortunately, the limited biomechanical knowledge of this injury prevents prophylactic measures from being developed that could reduce an athlete's risk of injury. The goal of this article is to summarize the literature on TMT dislocations, with a particular emphasis on the relevant biomechanics, in an attempt to clarify the circumstances and mechanisms under which these injuries occur. Since athletic injuries represent only a small portion of all TMT dislocations, other categories of injuries are also considered for the insight they provide. This review first summarizes the anatomy of the TMT joint as well as the clinical details surrounding TMT dislocations. The various hypothesized injury mechanisms are then reviewed with particular attention given to cadaveric studies that investigate these mechanisms. Based on this critical review, gaps in the research related to epidemiologic data, full-scale and component testing, numerical modeling, and countermeasure development, are identified. Only by improving our understanding of the causes and biomechanics can steps be taken to protect athletes from these injuries. PMID- 27278744 TI - The present state of the Japanese Society of Echocardiography: looking back on the 15th Annual. PMID- 27278745 TI - Left atrial wall motion velocity measured by the velocity profile method with tissue Doppler echocardiography in normal subjects: its relation to aging. AB - PURPOSE: The aim of this study was to find a method for measuring left atrial wall velocity (LAWV) during atrial contraction using tissue Doppler echocardiography. METHODS: The velocity profile method was used to measure left atrial wall velocity at several sites in 64 healthy individuals aged 25-84 years. We attempted to find maximum left atrial wall velocity (LAWVmax) by mapping on four-chamber, two-chamber, short-axis, and long-axis views and studied the relations between maximum left atrial wall velocity, age, and peak velocity during atrial contraction in mitral or pulmonary venous flow. RESULTS: Left atrial wall velocity was varied by changing the position of the sampling volume. The velocity profile pattern was similar to the left ventricular wall velocity pattern near the mitral valve annulus in the left atrium. Left atrial wall velocity had a positive peak during atrial contraction when the sample volume was located in the cranial and dorsal area. Maximum left atrial wall velocity was obtained in 74% of cases with the two-chamber view. Maximum left atrial wall velocity in healthy subjects was 3.1 +/- 0.7 cm/s, and the duration of the atrial contraction was 112 +/- 12 ms. Maximum left atrial wall velocity increased slightly with age but was not significantly correlated with peak velocity during atrial contraction in mitral or pulmonary venous flow. CONCLUSIONS: Left atrial wall velocity was measured by the velocity profile method in 64 healthy subjects aged 25-84 years. Maximum left atrial wall velocity increased slightly with age but was not significantly correlated with the peak velocity during atrial contraction in mitral or pulmonary venous flow. PMID- 27278746 TI - Classification of ultrasonographic images of small hepatocellular carcinoma using galactose-based contrast agent: relation between image patterns and histologic features. AB - PURPOSE: The aim of this study was to establish the relation between observed ultrasonographic (US) images produced with a galactose-based contrast agent and histologic characteristics of small hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: A total of 64 nodules in 64 patients, 22 well differentiated and 42 moderately differentiated with a histologically proven HCC, smaller than 3.0 cm in diameter and who had undergone hepatectomy were consecutively examined by contrast-enhanced US using a galactose-based contrast agent. Perfusion images were acquired by intermittent high-intensity, harmonic power Doppler sonography using a high pulse-repetition frequency and high-pass filter setting. Perfusion images of the arterial and late phases were classified into several patterns and compared with the histologic findings obtained from resected specimens. RESULTS: Most of the well- and moderately differentiated resected HCCs showed hyperechoic change during the arterial phase. However, 13 (59%) of the well-differentiated HCCs showed isoechoic change and 27 (64%) of the moderately differentiated HCCs showed hypoechoic change during the late phase. The difference is statistically significant (P < 0.0001). In a comparison of microscopic portal invasion (vp) of HCCs using enhanced US patterns, both vp(-) and vp(+) groups showed a high incidence of the hypervascular pattern during the arterial phase; in contrast, during the late phase 11 (73%) of 15 vp(+) nodules showed hypoechoic change with spotty signals. This difference is statistically significant (P < 0.0001) when compared with a high incidence (52%) of signal defect in the vp(-) group. The existence of well-differentiated components associated with the periphery of moderately differentiated HCCs also correlated closely with patterns during the late phase (P < 0.01). CONCLUSIONS: Late-phase contrast-enhanced US images of small HCCs with a galactose-based contrast agent are useful for predicting specific histologic characteristics. PMID- 27278747 TI - Characterization of secondary ultrasonic waves radiated by two oscillating bubbles. AB - PURPOSE: A bubble oscillating under an ultrasonic wave produces an interference sound field with the incident ultrasonic wave, forming fringe patterns of trapped microbubbles. We discuss secondary ultrasonic waves radiated by two oscillating bubbles in the incident ultrasonic wave in terms of both theory and experimental conditions. METHODS: Two oscillating bubbles produce an inherent secondary wave field that varies with the distance between the two bubbles and the phases of these waves. Here we discuss the Bjerknes force derived for two bubbles and microbubble trapping around the bubbles. The experiments were carried out using microbubbles produced with an ultrasonic contrast agent (Levovist). RESULTS AND CONCLUSIONS: The microbubble-trapping pattern observed around the bubbles in the experiment closely agrees with the numerical simulation. PMID- 27278748 TI - Atypical focal spared area in fatty liver: evaluation by color Doppler ultrasonography. AB - Ultrasonography often detects focal spared areas in fatty livers. One etiology was attributed to aberrant venous drainage. On ultrasonography images the lesions usually appear wedge-shaped, irregularly shaped, or, less frequently, round. We report a rare case of an irregular, hourglass-shaped focal spared area in segment IV of the liver resulting from the coexistence of an aberrant right gastric vein and anastomoses between the aberrant vein and the portal branches as well as a portohepatic venous shunt. PMID- 27278749 TI - Kinematic comparison of baseball batting off of a tee among various competition levels. AB - Determining and understanding baseball batting mechanics at various competition levels may help players and coaches identify key kinematics crucial to being a successful hitter. The purpose of this study was to compare batting kinematics across competition levels. Kinematic and temporal data were analysed for 170 male batters (youth n = 33; high school n = 69; college n = 22; professional n = 46) using 3D motion capture (480 Hz). The results showed differences in angular positions between competition levels during the five phases of the swing, with the greatest differences seen between the youth and professional batters. At the instant of ball contact, professional batters held the bat farther away from their body, with greater back shoulder abduction (35 degrees ) and less back elbow flexion (78 degrees ) compared to youth (27 degrees and 89 degrees , respectively). These differences were associated with greater back elbow extension velocity for professionals (1539 degrees /s) compared to youth (1174 degrees /s). Additionally, higher level batters had higher bat angular and linear velocities compared to the youth batters. As batters progress through their career, they should focus on their back arm by keeping their elbow up and their arm extended in front of them. PMID- 27278750 TI - MicroRNAs regulate T-cell production of interleukin-9 and identify hypoxia inducible factor-2alpha as an important regulator of T helper 9 and regulatory T cell differentiation. AB - MicroRNAs (miRNAs) regulate many aspects of helper T cell (Th) development and function. Here we found that they are required for the suppression of interleukin 9 (IL-9) expression in Th9 cells and other Th subsets. Two highly related miRNAs (miR-15b and miR-16) that we previously found to play an important role in regulatory T (Treg) cell differentiation were capable of suppressing IL-9 expression when they were over-expressed in Th9 cells. We used these miRNAs as tools to identify novel regulators of IL-9 expression and found that they could regulate the expression of Epas1, which encodes hypoxia-inducible factor (HIF) 2alpha. HIF proteins regulate metabolic pathway usage that is important in determining appropriate Th differentiation. The related protein, HIF-1alpha enhances Th17 differentiation and inhibits Treg cell differentiation. Here we found that HIF-2alpha was required for IL-9 expression in Th9 cells, but its expression was not sufficient in other Th subsets. Furthermore, HIF-2alpha suppressed Treg cell differentiation like HIF-1alpha, demonstrating both similar and distinct roles of the HIF proteins in Th differentiation and adding a further dimension to their function. Ironically, even though miR-15b and miR-16 suppressed HIF-2alpha expression in Treg cells, inhibiting their function in Treg cells did not lead to an increase in IL-9 expression. Therefore, the physiologically relevant miRNAs that regulate IL-9 expression in Treg cells and other subsets remain unknown. Nevertheless, the analysis of miR-15b and miR-16 function led to the discovery of the importance of HIF-2alpha so this work demonstrated the utility of studying miRNA function to identify novel regulatory pathways in helper T-cell development. PMID- 27278751 TI - Core-shell nanocarriers with high paclitaxel loading for passive and active targeting. AB - Rapid blood clearance and premature burst release are inherent drawbacks of conventional nanoparticles, resulting in poor tumor selectivity. iRGD peptide is widely recognized as an efficient cell membrane penetration peptide homing to alphaVbeta3 integrins. Herein, core-shell nanocapsules (NCs) and iRGD-modified NCs (iRGD-NCs) with high drug payload for paclitaxel (PTX) were prepared to enhance the antitumor activities of chemotherapy agents with poor water solubility. Improved in vitro and in vivo tumor targeting and penetration were observed with NCs and iRGD-NCs; the latter exhibited better antitumor activity because iRGD enhanced the accumulation and penetration of NCs in tumors. The NCs were cytocompatible, histocompatible, and non-toxic to other healthy tissues. The endocytosis of NCs was mediated by lipid rafts in an energy-dependent manner, leading to better cytotoxicity of PTX against cancer cells. In contrast with commercial product, PTX-loaded NCs (PTX-NCs) increased area under concentration time curve (AUC) by about 4-fold, prolonged mean resident time (MRT) by more than 8-fold and reduced the elimination rate constant by greater than 68-fold. In conclusion, the present nanocarriers with high drug-loading capacity represent an efficient tumor-targeting drug delivery system with promising potential for cancer therapy. PMID- 27278752 TI - The "self" in pain: the role of psychological inflexibility in chronic pain adjustment. AB - Self-discrepancy occurs when a person feels the failure to fulfill one's hopes or responsibilities. Although self-discrepancy has been widely examined to elucidate patients' chronic pain adjustment, the underlying mechanism is unclear. The present study proposes that the effect of self-discrepancy on pain outcomes is accounted for by psychological inflexibility, which involves the psychological processes that guide behaviors in the pursuit of goals and values. One-hundred patients with chronic pain were recruited from a public hospital. They were invited to participate in a semi-structured interview regarding their self discrepancy and complete self-reported questionnaires regarding their psychological inflexibility and pain outcomes. The results confirmed that psychological inflexibility partly accounts for the variance observed between self-discrepancy and pain outcomes. The current study provides additional insight into the mechanism underpinning the impact of self-discrepancy on patients' pain adjustment and offers clinical implications regarding the use of acceptance commitment therapy for chronic pain management. PMID- 27278753 TI - Alternol inhibits the proliferation and induces the differentiation of the mouse melanoma B16F0 cell line. AB - High malignant potential and low susceptibility to treatment are characteristics of malignant melanoma. Alternol, a novel compound purified from microbial fermentation products obtained from the bark of the yew tree, exhibits a variety of antitumor activities. Based on these findings, the aim of the present study was to extend the knowledge on the antineoplastic effect of alternol in the mouse melanoma B16F0 cell line. Alternol significantly inhibited the proliferation and colony formation of B16F0 cells in a dose-dependent manner as detected by MTT and soft agar colony formation assays. NaOH alkaline lysis and oxidation of Dopa indicated that alternol enhanced the melanin content and tyrosinase activity of the B16F0 cells and results also showed a dose-response relationship. Morphologic changes accompanied by extended dendrites were discovered in the B16F0 cells after treatment with alternol. Furthermore, the mRNA levels of tyrosinase, Trp1 and Trp2 were increased by alternol. Our results confirmed that alternol possesses marked antineoplastic properties against melanoma cells, indicating that this microbial fermentation product is a promising agent for the differentiation therapy of cancer. The inhibition of cell proliferation and colony formation by alternol was associated with both cytotoxicity and induction of differentiation. PMID- 27278754 TI - Preparing non-government organization workers to conduct health checks for people with serious mental illness in regional Australia. AB - WHAT IS KNOWN ON THE SUBJECT?: People diagnosed with schizophrenia or bipolar disorder have a life expectancy 10-15 years less than the general population. In rural and remote Australia, there is a shortage of health care professionals to provide physical health care for people living with a serious mental illness (SMI). A large proportion of the care for people living with a SMI is provided by non-government organizations (NGOs), often employing workers without formal qualifications. There has been minimal research regarding the experiences of NGO workers who have been trained to complete health checks to help people living with SMI to access primary care services. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first study to examine the experiences of preparing NGO workers to use the health improvement profile (HIP) to support the physical health of people with SMI. It builds on previous studies that examined the use of the HIP by trained/qualified staff. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This study highlights that NGO employees may have an important role in helping people with a SMI to address their physical health. Engaging lay workers to use the HIP increases their awareness of the importance of providing good physical health care for people with SMI. The use of a tool, such as the HIP, prepares NGO workers to support the physical health needs and enables them to describe meaningful improvements in the health of people with a SMI. ABSTRACT: Background The life expectancy of people living with a serious mental illness (SMI) is up to 10-15 years less than the general population. They experience difficulties in accessing timely and appropriate physical health care. People with SMI living in regional Australia experience additional barriers to accessing services. This is in part due to the difficulties associated with recruiting and retaining health professionals in regional Australia. Aim To explore the regional non-government organization (NGO) workforce views of using a physical health care check list - the health improvement profile (HIP) - with people with a SMI. Gain insights into the workers' experiences of using the HIP. Understand which aspects of the HIP workers perceived as being most and least helpful. Learn how the HIP and the training program could be modified to better support its application in regional Australia. Method A focus group using a semi-structured interview was conducted with seven NGO employees who had been trained to use the HIP and subsequently used the HIP in their everyday work with patients. A mental health nurse (MHN) and a Psychology graduate working for the University of South Australia Department of Rural Health conducted the focus group. Results Using thematic analysis, the focus group discussion generated four main themes: taking control; accessing services; guiding my conversation; and working with others. The overall meta-theme was that lay workers can work effectively to address physical health problems in SMI patients. Conclusion Our observations highlight the important role lay workers in regional Australia have in helping people with SMI to address their physical health needs. They have an opportunity to extend their role in parts of the world where it is difficult to recruit MHNs. PMID- 27278755 TI - MPs question whether adults with personal care budgets get best care. PMID- 27278756 TI - Optimal Trend Tests for Genetic Association Studies of Heterogeneous Diseases. AB - The Cochran-Armitage trend test is a standard procedure in genetic association studies. It is a directed test with high power to detect genetic effects that follow the gene-dosage model. In this paper, the author proposes optimal trend tests for genetic association studies of heterogeneous diseases. Monte-Carlo simulations show that the power gain of the optimal trend tests over the conventional Cochran-Armitage trend test is striking when the genetic effects are heterogeneous. The easy-to-use R 3.1.2 software (R Foundation for Statistical Computing, Vienna, Austria) code is provided. The optimal trend tests are recommended for routine use. PMID- 27278757 TI - Endothelins Inhibit Osmotic Swelling of Rat Retinal Glial and Bipolar Cells by Activation of Growth Factor Signaling. AB - Water accumulation in retinal glial (Muller) and neuronal cells resulting in cellular swelling contributes to the development of retinal edema and neurodegeneration. Here, we show that endothelin-1 (ET-1) dose-dependently inhibits the hypoosmotic swelling of Muller cells in freshly isolated retinal slices of control and diabetic rats, with a maximal inhibition at 100 nM. Osmotic Muller cell swelling was also inhibited by ET-2. The effect of ET-1 was mediated by activation of ETA and ETB receptors resulting in transactivation of metabotropic glutamate receptors, purinergic P2Y1, and adenosine A1 receptors. ET 1 (but not ET-2) also inhibited the osmotic swelling of bipolar cells in retinal slices, but failed to inhibit the swelling of freshly isolated bipolar cells. The inhibitory effect of ET-1 on the bipolar cell swelling in retinal slices was abrogated by inhibitors of the FGF receptor kinase (PD173074) and of TGF-beta1 superfamily activin receptor-like kinase receptors (SB431542), respectively. Both Muller and bipolar cells displayed immunoreactivities of ETA and ETB receptor proteins. The data may suggest that neuroprotective effects of ETs in the retina are in part mediated by prevention of the cytotoxic swelling of retinal glial and bipolar cells. ET-1 acts directly on Muller cells, while the inhibitory effect of ET-1 on bipolar cell swelling is indirectly mediated, via stimulation of the release of growth factors like bFGF and TGF-beta1 from Muller cells. PMID- 27278758 TI - Experimental Evidence that 3-Methylglutaric Acid Disturbs Mitochondrial Function and Induced Oxidative Stress in Rat Brain Synaptosomes: New Converging Mechanisms. AB - 3-Methylglutaric acid (3MGA) is an organic acid that accumulates in various organic acidemias whose patients present neurodegeneration events in children coursing with metabolic acidurias. Limited evidence describes the toxic mechanisms elicited by 3MGA in the brain. Herein, we explored the effects of 3MGA on different toxic endpoints in synaptosomal and mitochondrial-enriched fractions of adult rat brains to provide novel information on early mechanisms evoked by this metabolite. At 1 and 5 mM concentration, 3MGA increased lipid peroxidation, but decreased mitochondrial function only at 5 mM concentration. Despite less intense effects were obtained at 1 mM concentration, its co-administration with the kynurenine pathway (KP) metabolite and N-methyl-D-aspartate receptor (NMDAr) agonist, quinolinic acid (QUIN, 50 and 100 uM), produced toxic synergism on markers of oxidative stress and mitochondrial function. The toxicity of 3MGA per se (5 mM) was prevented by the cannabinoid receptor agonist WIN55,212-2 and the NMDAr antagonist kynurenic acid (KYNA), suggesting cannabinoid and glutamatergic components in the 3MGA pattern of toxicity. The synergic model (3MGA + QUIN) was also sensitive to KYNA and the antioxidant S-allylcysteine, but not to the nitric oxide synthase inhibitor L-nitroarginine methyl ester. These findings suggest various underlying mechanisms involved in the neurotoxicity of 3MGA that may possibly contribute to the neurodegeneration observed in acidemias. PMID- 27278759 TI - The Protein Tyrosine Kinase Inhibitor Tyrphostin 23 Strongly Accelerates Glycolytic Lactate Production in Cultured Primary Astrocytes. AB - Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases. To investigate potential acute effects of T23 on the viability and the glucose metabolism of brain cells, we exposed cultured primary rat astrocytes to T23 for up to 4 h. While the viability and the morphology of the cultured astrocytes were not acutely affected by the presence of T23 in concentrations of up to 300 uM, this compound caused a rapid, time- and concentration-dependent increase in glucose consumption and lactate release. Maximal effects on glycolytic flux were found for incubations with 100 uM T23 for 2 h which doubled both glucose consumption and lactate production. The stimulation of glycolytic flux by T23 was reversible, completely abolished upon removal of the compound and not found in presence of other known inhibitors of endocytosis. Structurally related compounds such as tyrphostin 25 and catechol or modulators of AMP kinase activity did neither affect the basal nor the T23-stimulated lactate production by astrocytes. In contrast, the presence of the phosphatase inhibitor vanadate completely abolished the stimulation by T23 of astrocytic lactate production in a concentration-dependent manner. These data suggest that T23-sensitive phosphorylation/dephosphorylation events are involved in the regulation of astrocytic glycolysis. PMID- 27278762 TI - Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study. AB - BACKGROUND: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. OBJECTIVE: While guided self help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. METHODS: This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to face/telephone/SkypeTM consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. RESULTS: The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. CONCLUSIONS: This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRTCTN): 22975026; http://www.isrctn.com/ISRCTN22975026 (Archived by WebCite at http://www.webcitation.org/6gBK00CUX). PMID- 27278760 TI - BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway. AB - Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT. PMID- 27278761 TI - Exploring developmental gene toolkit and associated pathways in a potential new model crustacean using transcriptomic analysis. AB - The crustaceans are one of the largest, most diverse, and most successful groups of invertebrates. The diversity among the crustaceans is also reflected in embryonic development models. However, the molecular genetics that regulates embryonic development is not known in those crustaceans that have a short germ band development with superficial cleavage, such as Macrobrachium olfersi. This species is a freshwater decapod and has great potential to become a model for developmental biology, as well as for evolutionary and environmental studies. To obtain sequence data of M. olfersi from an embryonic developmental perspective, we performed de novo assembly and annotation of the embryonic transcriptome. Using a pooling strategy of total RNA, paired-end Illumina sequencing, and assembly with multiple k-mers, a total of 25,636,097 pair reads were generated. In total, 99,751 unigenes were identified, and 20,893 of these returned a Blastx hit. KEGG pathway analysis mapped a total of 6866 unigenes related to 129 metabolic pathways. In general, 21,845 unigenes were assigned to gene ontology (GO) categories: molecular function (19,604), cellular components (10,254), and biological processes (13,841). Of these, 2142 unigenes were assigned to the developmental process category. More specifically, a total of 35 homologs of embryonic development toolkit genes were identified, which included maternal effect (one gene), gap (six), pair-rule (six), segment polarity (seven), Hox (four), Wnt (eight), and dorsoventral patterning genes (three). In addition, genes of developmental pathways were found, including TGF-beta, Wnt, Notch, MAPK, Hedgehog, Jak-STAT, VEGF, and ecdysteroid-inducible nuclear receptors. RT-PCR analysis of eight genes related to embryonic development from gastrulation to late morphogenesis/organogenesis confirmed the applicability of the transcriptome analysis. PMID- 27278764 TI - Type A: right atrial thrombus associated with a sub-massive pulmonary embolism. AB - The increased use of echocardiography in patients with pulmonary thrombo-embolic disease has led to the recognition of sub-massive pulmonary embolism (SMPE) and concurrent right-heart thrombus (RHT). When these findings coincide, they are associated with a poor prognosis, identifying a high-risk group that often requires a rapid management. Since echocardiographers become the "first responders" in this clinical scenario, it is important to raise awareness and familiarize the readers regarding the importance played by the echocardiography laboratory in the prompt diagnosis and management of this entity. We describe two patients presenting with SMPE with an associated simultaneous RHT and discuss their management. PMID- 27278763 TI - Diastolic asynchrony and myocardial dysfunction in patients with univentricular heart after Fontan operation. AB - BACKGROUND: We aimed to assess the existence of myocardial dysfunction and intra univentricular diastolic asynchrony in patients after Fontan operation. METHODS: Twenty patients after Fontan procedure and 30 age-matched controls were included in the study. The global function of the univentricular heart was analyzed by the Tei index. Regional myocardial velocities and strain of the univentricular heart including the rudimentary right ventricle (RV) were quantified by tissue Doppler imaging. Intra-univentricular or intra left ventricular (LV) diastolic delay was measured from the difference of diastolic intervals (time to peak early diastolic velocity), measured at LV lateral wall and the rudimental RV wall in patients, or LV lateral wall and the ventricular septum in controls. RESULTS: Compared to the control group, patients after Fontan operation had significantly elevated Tei index (0.24 +/- 0.02 vs. 0.41 +/- 0.1, p < 0.001). On the other hand, the regional myocardial velocities and strains of the univentricular heart including the rudimentary RV were significantly reduced (p < 0.001). Among patients, there was a significant correlation between the Tei index of the univentricular ventricle and rudimentary RV strain (r = -0.66, p = 0.01). The heart rate corrected intra-univentricular diastolic delay was significantly prolonged among patients when compared to the intra-LV diastolic delay in controls (0.01 +/- 0.9 vs. 1 +/- 1.1, p = 0.005). CONCLUSIONS: Myocardial dysfunctions and intra univentricular diastolic asynchrony of the univentricular heart in patients after Fontan procedure are evident. The rudimentary RV in patients after Fontan procedure plays an important role in the determination of the global function of the univentricular heart. PMID- 27278765 TI - Systemic lupus erythematosus and small vessel coronary infarction: who's to blame? AB - Systemic lupus erythematosus (SLE) with or without accompanying antiphospholipid antibody syndrome (APLS) is known to cause myocardial ischemia via multiple mechanisms, including accelerated coronary atherosclerosis, impaired coronary vasomotor function, spontaneous intracoronary thrombus formation, or endothelial dysfunction in the context of cardiac syndrome X (CSX). We present the case of a young woman with SLE and APLS who presented with myocardial ischemia and peculiar echocardiographic evidence of multiple small septal perforator infarcts despite a normal coronary angiogram, a rare combination. PMID- 27278766 TI - A case of carcinoid heart metastases. AB - Carcinoid tumor is an uncommon tumor that has often already developed metastases at the time of diagnosis. The primary site of tumors are the gastrointestinal tract, breast, and bronchus. The first manifestation of "carcinoid syndrome" occurs as a result of hormone production and cardiac involvement can be recognized in approximately half of the patients. The tricuspid or pulmonary valves are often affected, while, more rarely, the myocardial wall is of interest. A 51-year-old female patient affected by a primary pancreatic carcinoid showed interventricular septum carcinoid disease diagnosed by 2D echocardiography. PMID- 27278767 TI - Spontaneous dissection of the arterial duct during continuous infusion of prostaglandin E1 in a neonate with aortic arch interruption. AB - We report a 3-day-old boy with double outlet of the right ventricle and interruption of the aortic arch who developed spontaneous dissection of the arterial duct (DA) despite use of continuous infusion of lipo-prostaglandin E1 (PGE1). Transthoracic echocardiography demonstrated the spontaneous dissecting aneurysm of DA, which was confirmed by histology at the modified Norwood procedure done at age of 18 days. This is the first report of spontaneous dissection of DA in a neonate receiving PGE1, suggesting a new closing mechanism of DA. PMID- 27278768 TI - Patient with pseudo-retrograde coronary flow in the normal right coronary artery and left circumflex artery: pitfall of retrograde coronary flow to detect coronary artery occlusion. AB - A 75-year-old lady with hypertension and paroxysmal atrial fibrillation underwent echocardiography to evaluate cardiac function. Transthoracic Doppler echocardiography revealed retrograde coronary flow in the right coronary artery (RCA) and left circumflex artery (LCX). Computed tomographic coronary angiography demonstrated normal but tortuous coronary arteries. This tortuosity of the coronary arteries was thought be a cause of pseudo-retrograde coronary flow in the RCA and LCX. The present case demonstrates a pitfall of retrograde coronary flow for the detection of coronary artery occlusion in daily practice. PMID- 27278769 TI - Mid-diastolic mitral regurgitation in a patient with diastolic heart failure. PMID- 27278770 TI - Destructive acute infective endocarditis and purulent pericarditis. PMID- 27278771 TI - Deceased left ventricular compliance contributing to diastolic mitral regurgitation in a patient with atrioventricular block. PMID- 27278772 TI - Mid-diastolic mitral flow vectors in complete atrioventricular block. PMID- 27278773 TI - De novo sequencing and analysis of the transcriptome of Panax ginseng in the leaf expansion period. AB - Panax ginseng, a traditional Chinese medicine, is used worldwide for its variety of health benefits and its treatment efficacy. However, it is difficult to cultivate due to its vulnerability to environmental stresses. The present study provided the first report, to the best of our knowledge, of transcriptome analysis of ginseng at the leaf-expansion stage. Using the Illumina sequencing platform, >40,000,000 high-quality paired-end reads were obtained and assembled into 100,533 unique sequences. When the sequences were searched against the publicly available National Center for Biotechnology Information protein database using The Basic Local Alignment Search Tool, 61,599 sequences exhibited similarity to known proteins. Functional annotation and classification, including use of the Gene Ontology, Clusters of Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes databases, revealed that the activated genes in ginseng were predominantly ribonuclease-like storage genes, environmental stress genes, pathogenesis-related genes and other antioxidant genes. A number of candidate genes in environmental stress-associated pathways were also identified. These novel data provide useful information on the growth and development stages of ginseng, and serve as an important public information platform for further understanding of the molecular mechanisms and functional genomics of ginseng. PMID- 27278774 TI - Targeted, homology-driven gene insertion in stem cells by ZFN-loaded 'all-in-one' lentiviral vectors. AB - Biased integration remains a key challenge for gene therapy based on lentiviral vector technologies. Engineering of next-generation lentiviral vectors targeting safe genomic harbors for insertion is therefore of high relevance. In a previous paper (Cai et al., 2014a), we showed the use of integrase-defective lentiviral vectors (IDLVs) as carriers of complete gene repair kits consisting of zinc finger nuclease (ZFN) proteins and repair sequences, allowing gene correction by homologous recombination (HR). Here, we follow this strategy to engineer ZFN loaded IDLVs that insert transgenes by a homology-driven mechanism into safe loci. This insertion mechanism is driven by time-restricted exposure of treated cells to ZFNs. We show targeted gene integration in human stem cells, including CD34(+) hematopoietic progenitors and induced pluripotent stem cells (iPSCs). Notably, targeted insertions are identified in 89% of transduced iPSCs. Our findings demonstrate the applicability of nuclease-loaded 'all-in-one' IDLVs for site-directed gene insertion in stem cell-based gene therapies. PMID- 27278775 TI - Global, quantitative and dynamic mapping of protein subcellular localization. AB - Subcellular localization critically influences protein function, and cells control protein localization to regulate biological processes. We have developed and applied Dynamic Organellar Maps, a proteomic method that allows global mapping of protein translocation events. We initially used maps statically to generate a database with localization and absolute copy number information for over 8700 proteins from HeLa cells, approaching comprehensive coverage. All major organelles were resolved, with exceptional prediction accuracy (estimated at >92%). Combining spatial and abundance information yielded an unprecedented quantitative view of HeLa cell anatomy and organellar composition, at the protein level. We subsequently demonstrated the dynamic capabilities of the approach by capturing translocation events following EGF stimulation, which we integrated into a quantitative model. Dynamic Organellar Maps enable the proteome-wide analysis of physiological protein movements, without requiring any reagents specific to the investigated process, and will thus be widely applicable in cell biology. PMID- 27278776 TI - Erosive potential of vitamin and vitamin+mineral effervescent tablets. AB - The extrinsic sources for erosion-causing acids are primarily acidic beverages and foodstuffs. Effervescent tablets also contain organic acids (e.g. citric, tartaric, malic) in order to form carbon dioxide by contact with water ? with the help of the carbonate salts of the tablets. To adequately inform patients about the possible erosive potential of effervescent tablets, this study was undertaken in order to investigate the erosive potential of effervescent tablets (ET), containing either a combination of vitamins and minerals or vitamins only, commercially available in Switzerland. One hundred and ninety-two bovine enamel samples were prepared and allocated to 16 groups (A?H and 1?8; n = 12/group). Samples were eroded (120 s/erosive cycle) in freshly prepared solutions (200 ml/12 samples) comprised of tap water and a supplement as follows: none (control groups, A and 1); vitamin+mineral ET: Qualite and Prix (B), Optisana (C), Well and Active (D), Actilife All in One (E), Berocca (F), Isostar (G) and Qualite and Prix Mg + Vit C (H); vitamin ET: Actilife-Multivitamin (2), Sunlife Vitamin C (3), Optisana Vitamin C (4), Optisana Multivitamin (5), Well and Active Multivitamin (6), Kneipp Vitamin C+Zink (7) and Sunlife Multivitamin (8). Enamel loss was measured using profilometry after 10 and 20 erosive cycles. For the vitamin+mineral ET, no loss was observed in groups B?E. Significantly highest enamel loss (mean +/- SD) after 20 cycles was observed for Isostar (5.26 +/- 0.76 um) and Qualite and Prix Mg + Vit C (5.12 +/- 0.67 um). All vitamine ET showed erosive enamel loss. Significantly highest loss was observed for Sunlife Multivitamin (8.45 +/- 1.08 um), while the lowest loss was observed for Actilife Multivitamin (5.61 +/- 1.08 um) after 20 cycles. Some of the tested effervescent tablets showed a considerable erosive potential and patients should be informed accordingly. PMID- 27278777 TI - Association of early PSA decline and time to PSA progression in abiraterone acetate-treated metastatic castration-resistant prostate cancer; a post-hoc analysis of Japanese phase 2 trials. AB - BACKGROUND: Previous studies have demonstrated an association between prostate specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naive and chemotherapy-treated mCRPC patients receiving AA. METHODS: We used two Japanese phase II trial datasets: JPN-201, chemotherapy-naive mCRPC (n = 48) and JPN-202, chemotherapy treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP. RESULTS: PSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 +/- 5.6 and 2.0 +/- 3.4 months, and TTPP was 9.5 +/- 7.4 and 3.8 +/- 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan-Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (>=50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (>=30 %) at week 4 was not significant in JPN 201. CONCLUSIONS: Our results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy. TRIAL REGISTRATION: The original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201 , registered 20 December 2012 and JNJ-212082-JPN-202 , registered 30January 2013. PMID- 27278778 TI - Composition of the Cutaneous Bacterial Community in Japanese Amphibians: Effects of Captivity, Host Species, and Body Region. AB - The cutaneous microbiota plays a significant role in the biology of their vertebrate hosts, and its composition is known to be influenced both by host and environment, with captive conditions often altering alpha diversity. Here, we compare the cutaneous bacterial communities of 61 amphibians (both wild and captive) from Hiroshima, Japan, using high-throughput amplicon sequencing of a segment of the 16S rRNA gene. The majority of these samples came from a captive breeding facility at Hiroshima University where specimens from six species are maintained under highly standardized conditions for several generations. This allowed to identify host effects on the bacterial communities under near identical environmental conditions in captivity. We found the structure of the cutaneous bacterial community significantly differing between wild and captive individuals of newts, Cynops pyrrhogaster, with a higher alpha diversity found in the wild individuals. Community structure also showed distinct patterns when comparing different species of amphibians kept under highly similar conditions, revealing an intrinsic host effect. Bacterial communities of dorsal vs. ventral skin surfaces did not significantly differ in most species, but a trend of higher alpha diversity on the ventral surface was found in Oriental fire-bellied toads, Bombina orientalis. This study confirms the cutaneous microbiota of amphibians as a highly dynamic system influenced by a complex interplay of numerous factors. PMID- 27278779 TI - Urinary MCP-1 as a biomarker for lupus nephritis: a meta-analysis. AB - OBJECTIVE: This study aimed to evaluate whether urinary monocyte chemoattractant protein-1 (MCP-1) could serve as a biomarker for lupus nephritis (LN). METHODS: We performed a meta-analysis to examine the relationship between urinary MCP-1 level and LN in three comparisons: active LN versus inactive LN, active LN versus control, and inactive LN versus control. RESULTS: Eight studies of a total of 399 patients with LN (204 with active LN, and 195 with inactive LN) and 130 controls were available for this meta-analysis. The meta-analysis revealed that the urinary MCP-1 level was significantly higher in the active-LN group than in the inactive-LN group (standard mean difference [SMD] = 1.883, 95 % confidence interval [CI] = 0.811-2.954, p = 0.001). The meta-analysis showed that the urinary MCP-1 level was significantly higher in the active-LN group than in the control group (SMD = 3.085, 95 % CI = 1.684-4.485, p = 1.6 * 10-5). Furthermore, stratification by ethnicity showed significantly elevated urinary MCP-1 levels in the active-LN group in Caucasian, Asian, and Egyptian populations (SMD = 2.408, 95 % CI = 1.711-3.105, p < 1.0 * 10-8; SMD = 1.020, 95 % CI = 0.623-2.153, p = 4.6 * 10-7; and SMD = 7.370, 95 % CI = 1.467-2.157, p = 5.9 * 10-5, respectively). The meta-analysis indicated that the urinary MCP-1 level was also significantly higher in the inactive-LN group than in the control group (SMD = 1.812, 95 % CI = 0.628-2.996, p = 0.003). CONCLUSIONS: The meta-analysis demonstrated that urinary MCP-1 was significantly higher in patients with active LN than in those with inactive LN and control subjects, and the patients with inactive LN showed significantly higher urinary MCP-1 levels than the controls. PMID- 27278780 TI - [Treatment of chronic slipped capital femoral epiphysis : Use of dynamic epiphyseal telescopic screws]. AB - BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a multifactorial structural loosening in the area through the epiphyseal plate between the epiphysis and metaphysis accompanied by slippage of the femoral head in the mid dorsal-caudal direction without additional adequate trauma. In this retrospective study, all patients with chronic SCFE were assessed who had been treated by implanting a dynamic epiphyseal telescopic (DET) screw. METHODOLOGY: All patients who had been treated at our hospital with a DET screw implant between December 2006 and November 2014 following diagnosis of chronic SCFE were included in the study. Clinical and radiological follow-up was carried out after 6 weeks, 12 weeks, and then every 6 months. RESULTS: In all patients, the SCFE proved to have been firmly fixed and no further slippage was observed in any patient on the side affected. None of the prophylactically treated hips showed secondary SCFE either. In all patients, the DET screw led to partial remodeling of the slippage. The average slippage angle according to Southwick (epsilon angle) was about 30 degrees preoperatively and about 19 degrees in the most recent radiological follow-up. The alpha angle according to Notzli was about 91 degrees preoperatively and about 62 degrees in the most recent radiological follow-up. Most of the patients showed none treatment-related dysfunction. CONCLUSION: Surgical treatment with a DET screw seems to be a safe procedure for both the affected hip and the hip to be treated prophylactically. This method is an adequate alternative to the widespread technique of pinning with K-wires. PMID- 27278781 TI - Nanoassemblies constructed from bimodal mesoporous silica nanoparticles and surface-coated multilayer pH-responsive polymer for controlled delivery of ibuprofen. AB - The pH-sensitive poly(D-A) grafted amine-functionalized bimodal mesoporous silica (D-A/BMMs) was prepared by a facile method used as a drug delivery vehicle. They exhibited superior properties such as good dispersion in aqueous medium, high drug loading efficiency, improved stability and high drug release rates. Meanwhile, its structural features and performances in a controlled delivery of ibuprofen (IBU) were systematically investigated by using XRD, N2 adsorption and desorption, SEM, TEM, FT-IR, elemental analysis and TG techniques. The results demonstrated that the obtained nanocomposite presented a flexible control over drug release by controlling the grafting amount of D-A onto the mesopores surface of aminated BMMs. The cumulative percent release of IBU from D-A/BMMs was found to be much higher at pH 7.4 than at pH 2.0. The release rate was very slow in an acidic medium but became faster in a neutral medium, owing to hydrogen bonding in an acidic medium and electrostatic repulsion between negatively charged carboxyl groups in an alkaline medium. PMID- 27278782 TI - Hydroxyapatite microporous bioceramics as vancomycin reservoir: Antibacterial efficiency and biocompatibility investigation. AB - AbstarctInfections after bone reconstructive surgery are a real therapeutic and economic issue for the modern health care system. As the pathogen (most often Staphylococcus aureus) is able to develop a biofilm inside the bone, local delivery of antibiotics is of interest since high drug concentrations would be delivered directly at the target place. In this context, this study evaluated a porous hydroxyapatite implant as biocompatible bone substitute and vancomycin delivery system to prevent post-operative infections. A simple method of impregnation with optimised conditions insured a high antibiotic loading (up to 2.3 +/- 0.3 mg/m2), with a complete in vitro release obtained within 1-5 days. Additionally, the bacteriostatic and bactericidal effects of vancomycin were retained after loading on hydroxyapatite, as demonstrated after challenge with a Staphylococcus aureus strain. Regarding the biocompatibility, a wound healing assay of pre-osteoblastic MC3T3-E1 cells exposed to various concentrations of vancomycin revealed a dose-dependent reduction in cell migration for antibiotic concentrations higher than 1 mg/mL. Meanwhile, cells were able to proliferate normally on vancomycin-loaded scaffolds, although cell initial adhesion was seriously impaired for scaffolds loaded with 2.3 mg/m2 Loaded scaffolds could be stored up to three months at room temperature without any degradation of the antibiotic. Together, these results demonstrate the efficacy of these hydroxyapatite bone substitutes for local delivery of vancomycin in the context of bone infection. PMID- 27278783 TI - CNDP1 genotype and renal survival in pediatric nephropathies. AB - BACKGROUND: The risk of developing type II diabetic nephropathy (DN) is lower in patients carrying the CNDP1 Mannheim polymorphism (homozygosity for the five leucine repeat), resulting in decreased activity of the histidine-dipeptide metabolizing enzyme carnosinase. The role of CNDP1 in other nephropathies is still unknown. METHODS: To evaluate the impact of the CNDP1 Mannheim allele on pediatric chronic kidney disease (CKD), we prospectively followed the long-term clinical outcome of 272 children with non-diabetic kidney disease (glomerulopathies n=32, non-glomerular kidney disease n=240). RESULTS: Renal failure progression was independent of CNDP1 genotype in the total cohort of CKD children. However, in patients with glomerulopathies, only 39% of patients homozygous for the CNDP1 Mannheim polymorphism attained the primary renal endpoint as compared to 77% of patients with any other CNDP1 genotype (p=0.06). CONCLUSIONS: Our findings in pediatric CKD patients suggest that the nephroprotective effect of the CNDP1 Mannheim variant is not restricted to patients with diabetic nephropathy. PMID- 27278784 TI - Diagnostic interview study of the prevalence of depression among public employees engaged in long-term relief work in Fukushima. AB - AIM: The Great East Japan Earthquake and in particular, the Fukushima Daiichi Nuclear Power Plant accident, have had a serious psychological impact on not only residents, but also relief workers in Fukushima. Although public employees work in highly stressful situations and play a very important role in long-term relief, their psychiatric features have yet to be clarified. The two aims of this study were to identify the current prevalence rate of depression and post traumatic stress disorder among public employees working in the disaster area using diagnostic interviews, and to speculate on the psychosocial factors affecting their mental condition. METHODS: We conducted diagnostic interviews and self-administered questionnaires with 168 public employees working in two coastal towns in Fukushima. RESULTS: Results showed that the current prevalence of depression among public employees is as high as 17.9%, in contrast to the relatively low prevalence of post-traumatic stress disorder (4.8%). Based on the results of self-administered questionnaires and interview contents, frequent exposure to strong complaints or anger from residents and role conflicts were considered the cause of the high prevalence of depression. CONCLUSION: The present study reveals the serious mental status of public employees working in Fukushima and sheds light on the urgent need to establish an efficient care network to provide adequate psychiatric intervention. PMID- 27278786 TI - A descriptive analysis of midwifery education, regulation and association in 73 countries: the baseline for a post-2015 pathway. AB - BACKGROUND: Education, regulation and association (ERA) are the supporting pillars of an enabling environment for midwives to provide quality care. This study explores these three pillars in the 73 low- and middle-income countries who participated in the State of the World's Midwifery (SoWMy) 2014 report. It also examines the progress made since the previous report in 2011. METHODS: A self completion questionnaire collected quantitative and qualitative data on ERA characteristics and organisation in the 73 countries. The countries were grouped according to World Health Organization (WHO) regions. A descriptive analysis was conducted. RESULTS: In 82% of the participating countries, the minimum education level requirement to start midwifery training was grade 12 or above. The average length of training was higher for direct-entry programmes at 3.1 years than for post-nursing/healthcare provider programmes at 1.9 years. The median number of supervised births that must be conducted before graduation was 33 (range 0 to 240). Fewer than half of the countries had legislation recognising midwifery as an independent profession. This legislation was particularly lacking in the Western Pacific and South-East Asia regions. In most (90%) of the participating countries, governments were reported to have a regulatory role, but some reported challenges to the role being performed effectively. Professional associations were widely available to midwives in all regions although not all were exclusive to midwives. CONCLUSIONS: Compared with the 2011 SoWMy report, there is evidence of increasing effort in low- and middle-income countries to improve midwifery education, to strengthen the profession and to follow international ERA standards and guidelines. However, not all elements are being implemented equally; some variability persists between and within regions. The education pillar showed more systematic improvement in the type of programme and length of training. The reinforcement of regulation through the development of legislation for midwifery, a recognised definition and the strengthening of midwives' associations would benefit the development of other ERA elements and the profession generally. PMID- 27278787 TI - Detecting multiple variants associated with disease based on sequencing data of case-parent trios. AB - With the advance of next-generation sequencing technology, the rare variants join the common ones in explaining more proportions of heritability. The coexistence of variants of common with rare, causal with neutral and deleterious with protective is a norm and should be appropriately addressed. Some existing methods suffer from low power when one or more forms of coexistence present, impeding their applications in practice. In this paper, for case-parent trios, pseudocontrols are constructed using the nontransmitted alleles of the parents. The Kullback-Leibler divergence is utilized to measure the difference between the distributions of variants in a genetic region for the affected children and pseudocontrols, and two nonparametric test statistics KLTT and cKLTT are proposed. Extensive simulations show that they are robust to the opposite directions of the causal variants and the amount of neutral variants, and have superiority over the existing methods when both rare and common variants are involved. Furthermore, their efficiency is demonstrated in the application to the data from Framingham Heart Study. PMID- 27278788 TI - Regulation of metastasis-promoting LOXL2 gene expression by antitumor microRNAs in prostate cancer. AB - Our recent studies of microRNA (miRNA) expression signatures of prostate cancer (PCa) showed that six miRNAs (specifically, miR-26a, miR-26b, miR-29a, miR-29b, miR-29c and miR-218) were markedly reduced in cancer tissues. Moreover, ectopic expression of these miRNAs suppressed PCa cell aggressiveness, indicating that these miRNAs acted in concert to regulate genes that promoted metastasis. Genome wide gene expression analysis and in silico database analysis identified a total of 35 candidate genes that promoted metastasis and were targeted by these 6 miRNAs. Using luciferase reporter assays, we showed that the lysyl oxidase-like 2 (LOXL2) gene was directly controlled by these tumor-suppressive miRNAs in PCa cells. Overexpression of LOXL2 was confirmed in PCa tissues and knockdown of the LOXL2 gene markedly inhibited the migration and invasion of PCa cells. Aberrant expression of LOXL2 enhanced migration and invasion of PCa cells. Downregulation of antitumor miRNAs might disrupt the tightly controlled RNA networks found in normal cells. New insights into the novel molecular mechanisms of PCa pathogenesis was revealed by antitumor miRNA-regulated RNA networks. PMID- 27278789 TI - The roles of microRNAs in the progression of castration-resistant prostate cancer. AB - Prostate cancer (PCa) is one of the leading causes of cancer-related death in men. PCa is androgen-dependent, and androgen-deprivation therapy is effective for first-line hormonal treatment, but the androgen-independent phenotype of PCa eventually develops, which is difficult to treat and has no effective cure. Recently, microRNAs have been discovered to have important roles in the initiation and progression of PCa, suggesting their use in diagnosis, predicting prognosis and development of treatment for castration-resistant PCa (CRPC). Understanding the networks of microRNAs and their target genes is necessary to ascertain their roles and importance in the development and progression of PCa. This review summarizes the current knowledge about microRNAs regulating PCa progression and elucidates the mechanism of progression to CRPC. PMID- 27278791 TI - Outcome of microvascular decompression for hemifacial spasm associated with the vertebral artery. AB - We retrospectively compared the outcome of microvascular decompression (MVD) for hemifacial spasm (HFS) associated with the vertebral artery (VA) with that of MVD for HFS unrelated to the VA. Between April 2008 and April 2015, 22 patients with VA-associated HFS underwent MVD at our institution. The median follow-up period was 28 months (range, 12-90 months). Results were classified as excellent in 19 patients (86 %), good in one (5 %), fair in one (5 %), and poor in one (5 %). Immediate complications developed in five patients (23 %), and one of these complications (5 %) was permanent. The surgical outcome of MVD for VA-associated HFS was similar to that of MVD for HFS unrelated to the VA; however, the incidence of complications was significantly more frequent in patients whose VA compressed the more proximal portion of the facial nerve root exit zone from the caudal side at the pontomedullary sulcus. We conclude that preoperative evaluation of VA compression patterns is important to predict the difficulty of the planned MVD procedure. PMID- 27278792 TI - Neural signals of vicarious extinction learning. AB - Social transmission of both threat and safety is ubiquitous, but little is known about the neural circuitry underlying vicarious safety learning. This is surprising given that these processes are critical to flexibly adapt to a changeable environment. To address how the expression of previously learned fears can be modified by the transmission of social information, two conditioned stimuli (CS + s) were paired with shock and the third was not. During extinction, we held constant the amount of direct, non-reinforced, exposure to the CSs (i.e. direct extinction), and critically varied whether another individual-acting as a demonstrator-experienced safety (CS + vic safety) or aversive reinforcement (CS + vic reinf). During extinction, ventromedial prefrontal cortex (vmPFC) responses to the CS + vic reinf increased but decreased to the CS + vic safety This pattern of vmPFC activity was reversed during a subsequent fear reinstatement test, suggesting a temporal shift in the involvement of the vmPFC. Moreover, only the CS + vic reinf association recovered. Our data suggest that vicarious extinction prevents the return of conditioned fear responses, and that this efficacy is reflected by diminished vmPFC involvement during extinction learning. The present findings may have important implications for understanding how social information influences the persistence of fear memories in individuals suffering from emotional disorders. PMID- 27278790 TI - Noncoding RNA and colorectal cancer: its epigenetic role. AB - The use of novel sequencing and high-throughput techniques has become widespread, and are now readily available to obtain the comprehensive transcription profile of the human genome. Noncoding RNAs (ncRNAs) are transcripts that have no apparent protein-coding capacity, but they have important roles in human physiology. Most research in this area has focused on micro-RNAs. However, the role of long ncRNAs (lncRNAs) as drivers of tumor suppression and oncogenic functions has recently been examined in numerous cancer types. Epigenetic alterations can reportedly deregulate the expression of any type of transcript. However, the exact mechanisms of epigenetic regulation of lncRNA are still unknown. In this review, the authors primarily focus on the epigenetic effects modulating ncRNA in colorectal cancer (CRC). The authors specifically discuss examples of oncogenic ncRNA in CRC pathobiology, as well as its extended diagnosis, prognosis and therapy. PMID- 27278793 TI - Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study. AB - BACKGROUND: Cardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation. METHODS: The study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP >=61 %) were compared. RESULTS: The mean PRI VASP value was significantly higher in the transplant group (60.1 +/- 3 vs 51.2 +/- 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03-6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status. CONCLUSIONS: KT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population. PMID- 27278794 TI - Modelling estimates of age-specific influenza-related hospitalisation and mortality in the United Kingdom. AB - BACKGROUND: Influenza is rarely confirmed with laboratory testing and accurate assessment of the overall burden of influenza is difficult. We used statistical modelling methods to generate updated, granular estimates of the number/rate of influenza-attributable hospitalisations and deaths in the United Kingdom. Such data are needed on a continuing basis to inform on cost-benefit analyses of treatment interventions, including vaccination. METHODS: Weekly age specific data on hospital admissions (1997-2009) and on deaths (1997-2009) were obtained from national databases. Virology reports (1996-2009) of influenza and respiratory syncytial virus detections were provided by Public Health England. We used an expanded set of ICD-codes to estimate the burden of illness attributable to influenza which we refer to as 'respiratory disease broadly defined'. These codes were chosen to optimise the balance between sensitivity and specificity. A multiple linear regression model controlled for respiratory syncytial virus circulation, with stratification by age and the presence of comorbid risk status (conditions associated with severe influenza outcomes). RESULTS: In the United Kingdom there were 28,516 hospitalisations and 7163 deaths estimated to be attributable to influenza respiratory disease in a mean season, with marked variability between seasons. The highest incidence rates of influenza attributable hospitalisations and deaths were observed in adults aged 75+ years (252/100,000 and 131/100,000 population, respectively). Influenza B hospitalisations were highest among 5-17 year olds (12/100,000 population). Of all estimated influenza respiratory deaths in 75+ year olds, 50 % occurred out of hospital, and 25 % in 50-64 year olds. Rates of hospitalisations and death due to influenza-attributable respiratory disease were increased in adults identified as at-risk. CONCLUSIONS: Our study points to a substantial but highly variable seasonal influenza burden in all age groups, particularly affecting 75+ year olds. Effective influenza prevention or early intervention with anti-viral treatment in this age group may substantially impact the disease burden and associated healthcare costs. The high burden of influenza B hospitalisation among 5-17 year olds supports current United Kingdom vaccine policy to extend quadrivalent seasonal influenza vaccination to this age group. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01520935. PMID- 27278795 TI - Highly selective and sensitive phosphate anion sensors based on AlGaN/GaN high electron mobility transistors functionalized by ion imprinted polymer. AB - A novel ion-imprinted electrochemical sensor based on AlGaN/GaN high electron mobility transistors (HEMTs) was developed to detect trace amounts of phosphate anion. This sensor combined the advantages of the ion sensitivity of AlGaN/GaN HEMTs and specific recognition of ion imprinted polymers. The current response showed that the fabricated sensor is highly sensitive and selective to phosphate anions. The current change exhibited approximate linear dependence for phosphate concentration from 0.02 mg L(-1) to 2 mg L(-1), the sensitivity and detection limit of the sensor is 3.191 MUA/mg L(-1) and 1.97 MUg L(-1), respectively. The results indicated that this AlGaN/GaN HEMT-based electrochemical sensor has the potential applications on phosphate anion detection. PMID- 27278796 TI - Reliability and validity of the Khmer version of the 10-item Connor-Davidson Resilience Scale (Kh-CD-RISC10) in Cambodian adolescents. AB - BACKGROUND: Resilience has been characterized as a defensive factor against the refinement of mental health problems. This study adapted the Connor-Davidson Resilience Scale (Kh-CD-RISC10) for use in Khmer adolescents and subsequently investigates its psychometric properties. METHODS: Using stratified random sampling, this cross-sectional study sampled Cambodian adolescents from high schools selected randomly within three provinces (Phnom Penh, Battambang and Mondulkiri)-location (rural, urban) combinations. Parallel analysis was used to identify the number of component(s), and the structure of the single factor was subsequently explored using principal axis factoring. A confirmatory factor analysis was then performed to establish the fit of the Kh-CD-RISC10 to another sample. To assess convergent validity, the factor scores of the Khmer version of Connor-Davidson Resilience Scale were categorized into three levels, and then the general negative affectivity (GNA) and physiological hyperarousal (PH) scales (derived from the DASS 21) were compared among the three resilience groups. RESULTS: Of the 798 participants who responded (responded rate = 82.26 %), 440 (41.23 %) were female and the age ranged from 14 to 24 years old (mean = 17.36, SD = 1.325). The internal consistency of the Khmer 10-item CD-RISC was also shown to be high in Cambodian adolescents (Cronbach's alpha = 0. 82). Confirmatory factor analysis revealed the single factor model fit data adequately (chi(2) = 100.103, df = 35, p < 0.001, CFI = 0.9484, RMSEA = 0.0384). We found that there were significant differences in both General Negative affectivity and Physiological Hyperarousal among the three resilience groups (FGNA = 12. 84, df = 2, p < 0.001; FPH = 13. 01, df = 2, p < 0.001). CONCLUSION: The results from the present study indicate that the Khmer version of CD-RISC shows good psychometric properties in Cambodian adolescents. Our result confirms that a single dimension underlay the 10 items on the CD-RISC scale of this population, and can be used to assess the resilience comparing to the level of PTSD symptoms in general Khmer adolescent. PMID- 27278797 TI - Diastology 2010: clinical approach to diastolic heart failure. AB - The role of echocardiography in the evaluation of left ventricular diastolic function is increasingly important in both systolic and diastolic heart failure. In routine clinical practice, the diastolic dysfunction associated with diastolic heart failure can mainly be evaluated by Doppler echocardiography. In order to use echocardiographic techniques for this purpose, one should recognize the definition, terminology, epidemiology, and pathophysiology of diastolic dysfunction and diastolic heart failure. There are various echocardiographic parameters for this purpose, including transmitral flow velocity, pulmonary venous flow velocity, mitral annular velocity, flow propagation velocity, left atrial size, strain, strain rate, twist, and so on. However, no single Doppler echocardiographic index has yielded a robust criterion for diastolic dysfunction and elevated left ventricular filling pressure. Thus, multiple indices are required to increase the sensitivity of the diagnosis. Clinicians who take care of heart failure patients should continue to make critical use of a current Doppler echocardiographic evaluation and utilize this information to improve survival and quality of life in these patients. PMID- 27278798 TI - Is the E/V p index useful for evaluating prognosis in chronic heart failure with atrial fibrillation? A pilot study. AB - BACKGROUND: The ratio of transmitral peak E wave velocity to color flow propagation velocity (E/V p index) has proved to be a significant predictor of prognosis in cardiac diseases with sinus rhythm. However, its usefulness in patients with atrial fibrillation (AF) and heart failure has not yet been established. The aim of this study was to determine the feasibility of using the E/V p index for the prediction of mortality and heart failure hospitalization in this group. METHODS: We studied 66 ambulatory patients with stable congestive heart failure (CHF) functional class I-III and AF. Patients were divided into group A and B according to an E/V p index <1.5 and >=1.5, respectively. RESULTS: During follow-up (average 430 days) events were more common in group B (75 vs. 17%, log rank test; hazard ratio (HR) = 6.8). By means of multivariate logistic regression analysis, E/V p proved to be an independent predictor of events (p = 0.0012). CONCLUSIONS: In our patients with stable CHF and AF the E/V p index is a significant predictor of clinical outcome. PMID- 27278799 TI - Relation between progression of aortic valve sclerosis and carotid intima-media thickening in asymptomatic subjects with cardiovascular risk factors. AB - BACKGROUND: Aortic valve sclerosis (AVS) is the early lesion of calcific aortic valve disease and may subsequently progress toward valvular stenosis. Histopathological and clinical evidence has suggested that AVS and atherosclerosis share similar mechanisms. However, little is known regarding the relation between the early AVS progression and the early atherosclerosis progression. The carotid intima-media thickness (IMT) by carotid ultrasonography has been established as the surrogate marker of the early atherosclerosis. The aim of this study was to examine the association between progression of early AVS and increase of carotid IMT. METHODS: We retrospectively analyzed the data of 127 asymptomatic subjects (49 +/- 8 years, 114 men) with >=1 cardiovascular (CV) risk factors, without history of CV disease, who underwent echocardiographic and carotid ultrasonographic examinations twice >=6 months apart. We evaluated aortic valve morphology and function and carotid IMT at the baseline and at follow-up examinations. RESULTS: During a follow-up of 25 +/- 15 months, the number of subjects with AVS was significantly increased (34 vs. 47%, P < 0.0001) and the mean value of carotid IMT was significantly increased (1.16 +/- 0.33 vs. 1.29 +/- 0.41 mm, P < 0.0001). The progression of AVS was observed in 26 subjects. By logistic regression analysis, the baseline carotid IMT value was an independent predictor of AVS progression (odds ratio = 4.07, P = 0.026). CONCLUSION: In asymptomatic subjects with CV risk factors, progression of AVS and increase of carotid IMT were observed during a mean follow-up period of 25 months. Progression of AVS in asymptomatic subjects with CV risk factors was associated with carotid intima-media thickening. PMID- 27278800 TI - Imaging of aortico-left ventricular tunnel by three-dimensional echocardiography. AB - Aortico-left ventricular tunnel (ALVT) is a rare congenital heart disease presenting as congestive heart failure in the neonatal or early infantile period due to severe aortic regurgitation (AR). We presented a 1-month-old boy with ALVT, originally diagnosed by two-dimensional echocardiography; however, the detailed anatomical features were not ascertained. Real-time three-dimensional echocardiography (RT3DE) could provide clear images of the three-dimensional structures of ALVT, just the same as those of surgical findings. ALVT originated from the left coronary cusp and ran an oblique path to the subvalvular orifice, having a narrow segment in the middle. RT3DE is a clinically useful diagnostic tool to clarify the detailed anatomy of ALVT. PMID- 27278801 TI - Exercise echocardiography in the evaluation of severity of functional mitral regurgitation in patients with heart failure. AB - We present two cases with ischemic cardiomyopathy and similar functional mitral regurgitation (fMR) at rest, who represented different outcomes following mitral valve repair. In case 1, fMR was enhanced during exercise echocardiography, and his symptoms were improved following the repair and coronary artery bypass graft (CABG). In case 2, fMR did not change during exercise, and the improvement of his symptoms was small following the operation. Exercise echocardiography evidenced variability of the dynamic changes in fMR in patients with ischemic cardiomyopathy. The variability may be related to the outcome of the mitral valve repair. PMID- 27278802 TI - Distal lower limb strength is reduced in subjects with impaired glucose tolerance and is related to elevated intramuscular fat level and vitamin D deficiency. AB - AIM: To quantify muscle strength and size in subjects with impaired glucose tolerance (IGT) in relation to intramuscular non-contractile tissue, the severity of neuropathy and vitamin D level. METHODS: A total of 20 subjects with impaired glucose tolerance and 20 control subjects underwent assessment of strength and size of knee extensor, flexor and ankle plantar and dorsi-flexor muscles, as well as quantification of intramuscular non-contractile tissue and detailed assessment of neuropathy and serum 25-hydroxy vitamin D levels. RESULTS: In subjects with impaired glucose tolerance, proximal knee extensor strength (P = 0.17) and volume (P = 0.77), and knee flexor volume (P = 0.97) did not differ from those in control subjects. Ankle plantar flexor strength was significantly lower (P = 0.04) in the subjects with impaired glucose tolerance, with no difference in ankle plantar flexor (P = 0.62) or dorsiflexor volume (P = 0.06) between groups. Intramuscular non-contractile tissue level was significantly higher in the ankle plantar flexors and dorsiflexors (P = 0.03) of subjects with impaired glucose tolerance compared with control subjects, and it correlated with the severity of neuropathy. Ankle plantar flexor muscle strength correlated significantly with corneal nerve fibre density (r = 0.53; P = 0.01), a sensitive measure of small fibre neuropathy, and was significantly lower in subjects with vitamin D deficiency (P = 0.02). CONCLUSIONS: People with impaired glucose tolerance have a significant reduction in distal but not proximal leg muscle strength, which is not associated with muscle atrophy, but with increased distal intramuscular non contractile tissue, small fibre neuropathy and vitamin D deficiency. PMID- 27278803 TI - Post-exercise cold water immersion does not alter high intensity interval training-induced exercise performance and Hsp72 responses, but enhances mitochondrial markers. AB - This study aims to evaluate the effect of regular post-exercise cold water immersion (CWI) on intramuscular markers of cellular stress response and signaling molecules related to mitochondria biogenesis and exercise performance after 4 weeks of high intensity interval training (HIIT). Seventeen healthy subjects were allocated into two groups: control (CON, n = 9) or CWI (n = 8). Each HIIT session consisted of 8-12 cycling exercise stimuli (90-110 % of peak power) for 60 s followed by 75 s of active recovery three times per week, for 4 weeks (12 HIIT sessions). After each HIIT session, the CWI had their lower limbs immersed in cold water (10 degrees C) for 15 min and the CON recovered at room temperature. Exercise performance was evaluated before and after HIIT by a 15-km cycling time trial. Vastus lateralis biopsies were obtained pre and 72 h post training. Samples were analyzed for heat shock protein 72 kDa (Hsp72), adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated p38 mitogen activated protein kinase (p-p38 MAPK) assessed by western blot. In addition, the mRNA expression of heat shock factor-1 (HSF-1), peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), nuclear respiratory factor 1 and 2 (NRF1 and 2), mitochondrial transcription factor A (Tfam), calcium calmodulin dependent protein kinase 2 (CaMK2) and enzymes citrate synthase (CS), carnitine palmitoyltransferase I (CPT1), and pyruvate dehydrogenase kinase (PDK4) were assessed by real-time PCR. Time to complete the 15-km cycling time trial was reduced with training (p < 0.001), but was not different between groups (p = 0.33). The Hsp72 (p = 0.01), p38 MAPK, and AMPK (p = 0.04) contents increased with training, but were not different between groups (p > 0.05). No differences were observed with training or condition for mRNA expression of PGC-1alpha (p = 0.31), CPT1 (p = 0.14), CS (p = 0.44), and NRF-2 (p = 0.82). However, HFS-1 (p = 0.007), PDK4 (p = 0.03), and Tfam (p = 0.03) mRNA were higher in CWI. NRF-1 decrease in both groups after training (p = 0.006). CaMK2 decreased with HIIT (p = 0.003) but it was not affected by CWI (p = 0.99). Cold water immersion does not alter HIIT-induced Hsp72, AMPK, p38 MAPK, and exercise performance but was able to increase some markers of cellular stress response and signaling molecules related to mitochondria biogenesis. PMID- 27278804 TI - Effects of salinity acclimation and eyestalk ablation on Na(+), K(+), 2Cl(-) cotransporter gene expression in the gill of Portunus trituberculatus:a molecular correlate for salt-tolerant trait. AB - The Na(+), K(+), 2Cl(-) cotransporter (NKCC) is an important gene in ion transport. In order to elucidate its function, and regulatory mechanisms, in salinity acclimation, the complete cDNA sequence of NKCC (4218 bp) from Portunus trituberculatus (PtNKCC) was first cloned and characterized. It was found to encode 1055 amino acids containing conserved AA-permease and SLC12 motifs. Results show that PtNKCC is expressed to the greatest extent in gills. High salinity stress exposure led to significant increases (9.6-fold) of PtNKCC mRNA expression in the gills 12 h after treatment, declining to less than the levels seen in the control group between 48 and 72 h. During low salinity stress, expression levels of PtNKCC in gills were found to be upregulated at each sampling time, reaching their peak after 6 h (a 12.4-fold increase). Eyestalk ablation also triggered an 11.3-fold increase in PtNKCC mRNA, while re-injection with eyestalk homogenates significantly reduced the expression of PtNKCC mRNA. Four single nucleotide polymorphisms (SNPs) were detected in the PtNKCC open reading frame, and one SNP was associated with salt tolerance. Our results indicate that PtNKCC plays an important role in the salinity acclimation of P. trituberculatus, while there may be a compound present in the XOSG that inhibits the expression of PtNKCC. PMID- 27278805 TI - Photo Inactivation of Streptococcus mutans Biofilm by Violet-Blue light. AB - Among various preventive approaches, non-invasive phototherapy/photodynamic therapy is one of the methods used to control oral biofilm. Studies indicate that light at specific wavelengths has a potent antibacterial effect. The objective of this study was to determine the effectiveness of violet-blue light at 380-440 nm to inhibit biofilm formation of Streptococcus mutans or kill S. mutans. S. mutans UA159 biofilm cells were grown for 12-16 h in 96-well flat-bottom microtiter plates using tryptic soy broth (TSB) or TSB with 1 % sucrose (TSBS). Biofilm was irradiated with violet-blue light for 5 min. After exposure, plates were re incubated at 37 degrees C for either 2 or 6 h to allow the bacteria to recover. A crystal violet biofilm assay was used to determine relative densities of the biofilm cells grown in TSB, but not in TSBS, exposed to violet-blue light. The results indicated a statistically significant (P < 0.05) decrease compared to the non-treated groups after the 2 or 6 h recovery period. Growth rates of planktonic and biofilm cells indicated a significant reduction in the growth rate of the violet-blue light-treated groups grown in TSB and TSBS. Biofilm viability assays confirmed a statistically significant difference between violet-blue light treated and non-treated groups in TSB and TSBS. Visible violet-blue light of the electromagnetic spectrum has the ability to inhibit S. mutans growth and reduce the formation of S. mutans biofilm. This in vitro study demonstrated that violet blue light has the capacity to inhibit S. mutans biofilm formation. Potential clinical applications of light therapy in the future remain bright in preventing the development and progression of dental caries. PMID- 27278806 TI - Differential Response of Extracellular Proteases of Trichoderma Harzianum Against Fungal Phytopathogens. AB - In the present study, production of extracellular proteases by Trichoderma harzianum was evaluated based on the relative gene expression and spectrophotometric assay. The fungal isolates were grown in Czapek Dox Broth medium supplemented with deactivated mycelium of plant fungal pathogens such as Fusarium oxysporum, Colletotrichum capsici, Gloeocercospora sorghi, and Colletotrichum truncatum. The maximum protease activity was detected after 48 h of incubation against Colletotrichum spp. Similarly in qRT-PCR, the relative gene expression of four proteases varied from 48 to 96 h against host pathogens in a time-independent manner. Among proteases, statistically significant upregulation of asp, asp, and srp was observed against Colletotrichum spp., followed by F. oxysporum. But in the case of pepM22, maximum upregulation was observed against F. oxysporum. The variation in enzyme assay and qRT-PCR of proteases at different time intervals against various fungal phytopathogens could be due to the limitation of using casein as a substrate for all types of proteases or protease encoding transcripts selected for qRT-PCR, which may not be true representative of total protease activity. PMID- 27278807 TI - Outcome in dogs with advanced (stage 3b) anal sac gland carcinoma treated with surgery or hypofractionated radiation therapy. AB - Stage 3b anal sac gland carcinoma (ASGC) can be life-threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 * 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression-free interval (PFI) and median survival time (MST) were compared. Twenty-eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life-threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135-184 days) and 182 days (95% CI: 146-218 days), both significantly lower than for RT cases with 347 days (95% CI: 240-454 days) and 447 days (95% CI: 222-672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT. PMID- 27278809 TI - Correction to "1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N methylmethanamine Monofumarate (TAK-438), a Novel and Potent Potassium Competitive Acid Blocker for the Treatment of Acid-Related Diseases.". PMID- 27278808 TI - Atomic layer deposition coating of carbon nanotubes with zinc oxide causes acute phase immune responses in human monocytes in vitro and in mice after pulmonary exposure. AB - BACKGROUND: Atomic layer deposition (ALD) is a method for applying conformal nanoscale coatings on three-dimensional structures. We hypothesized that surface functionalization of multi-walled carbon nanotubes (MWCNTs) with polycrystalline ZnO by ALD would alter pro-inflammatory cytokine expression by human monocytes in vitro and modulate the lung and systemic immune response following oropharyngeal aspiration in mice. METHODS: Pristine (U-MWCNTs) were coated with alternating doses of diethyl zinc and water over increasing ALD cycles (10 to 100 ALD cycles) to yield conformal ZnO-coated MWCNTs (Z-MWCNTs). Human THP-1 monocytic cells were exposed to U-MWCNTs or Z-MWCNTs in vitro and cytokine mRNAs measured by Taqman real-time RT-PCR. Male C57BL6 mice were exposed to U- or Z-MWCNTs by oropharyngeal aspiration (OPA) and lung inflammation evaluated at one day post exposure by histopathology, cytokine expression and differential counting of cells in bronchoalveolar lavage fluid (BALF) cells. Lung fibrosis was evaluated at 28 days. Cytokine mRNAs (IL-6, IL-1beta, CXCL10, TNF-alpha) in lung, heart, spleen, and liver were quantified at one and 28 days. DNA synthesis in lung tissue was measured by bromodeoxyuridine (BrdU) uptake. RESULTS: ALD resulted in a conformal coating of MWCNTs with ZnO that increased proportionally to the number of coating cycles. Z-MWCNTs released Zn(+2) ions in media and increased IL 6, IL-1beta, CXCL10, and TNF-alpha mRNAs in THP-1 cells in vitro. Mice exposed to Z-MWCNTs by OPA had exaggerated lung inflammation and a 3-fold increase in monocytes and neutrophils in BALF compared to U-MWCNTs. Z-MWCNTs, but not U MWCNTs, induced IL-6 and CXCL10 mRNA and protein in the lungs of mice and increased IL-6 mRNA in heart and liver. U-MWCNTs but not Z-MWCNTs stimulated airway epithelial DNA synthesis in vivo. Lung fibrosis at 28 days was not significantly different between mice treated with U-MWCNT or Z-MWCNT. CONCLUSIONS: Pulmonary exposure to ZnO-coated MWCNTs produces a systemic acute phase response that involves the release of Zn(+2), lung epithelial growth arrest, and increased IL-6. ALD functionalization with ZnO generates MWCNTs that possess increased risk for human exposure. PMID- 27278810 TI - Pyrogallol induces the death of human pulmonary fibroblast cells through ROS increase and GSH depletion. AB - Pyrogallol (PG) inhibits the growth of various cells via stimulating O2*- mediated death. This study investigated the effects of PG on cell death in human pulmonary fibroblast (HPF) cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. PG inhibited the growth of HPF cells with an IC50 of ~50-100 uM at 24 h. PG induced a G1 phase arrest of the cell cycle and also triggered cell death accompanied by the loss of mitochondrial membrane potential (MMP; ?psim), Bcl-2 decrease, p53 increase and the activation of caspase-3. PG increased O2*- level in HPF cells and depleted GSH content in these cells. Z-VAD (a pan-caspase inhibitor) did not significantly change cell growth inhibition, death and MMP (?psim) loss in PG-treated HPF cells. N-acetylcysteine (NAC) attenuated growth inhibition, death and MMP (?psim) loss in PG-treated HPF cells and it decreased O2*- level in these cells as well. However, L-buthionine sulfoximine (BSO) strongly increased ROS level in PG-treated HPF cells and it intensified growth inhibition, cell death, MMP (?psim) loss and GSH depletion in these cells. In conclusion, PG-induced HPF cell death was closely related to increases in ROS level and GSH depletion. PMID- 27278811 TI - Taking a Third-Person Perspective Requires Inhibitory Control: Evidence From a Developmental Negative Priming Study. AB - To determine whether the growing ability to take a third-person perspective (3PP) is explained in part by the growing ability to inhibit a first-person perspective (1PP), 10-year-old children (n = 49) and 22-year-old adults (n = 52) performed a negative priming adaptation of the own body transformation task. Both children and adults were less efficient in adopting a 1PP after they adopted a 3PP-with a smaller amplitude of the negative priming effect with older age-and adults' and children's performances in the own body transformation task were predicted in part by their Stroop interference scores. These results suggest that the growing efficiency to adopt a 3PP is rooted in part in the growing efficiency to inhibit the 1PP. PMID- 27278813 TI - On the importance of tetrel bonding interactions in lead(ii) complexes with (iso)nicotinohydrazide based ligands and several anions. AB - Four Pb(ii) complexes of (iso)nicotinohydrazide-based ligands and different anionic coligands (azide, nitrate, acetate and iodide) have been synthesized and characterized by structural, analytical and spectroscopic methods. The mono deprotonated or neutral forms of the ligands coordinate in a tridentate fashion via two nitrogen and one oxygen donor atoms to the Pb. Single-crystal X-ray crystallography showed that the molecular complexes can aggregate into larger entities depending upon the anion coordinated to the metal centre. In all four complexes the lead center is hemidirectionally coordinated and, consequently, it is sterically ideal for establishing tetrel bonding interactions. In the crystal structures of all complexes, the lead atoms participate in short contacts with nitrogen atoms. These contacts are shorter than the sums of the van der Waals radii and larger than the sums of the covalent radii. The tetrel bonding interactions interconnect the covalently bonded units (monomers or dimers) into supramolecular assemblies (chains and 3D structures). We have analysed the interesting supramolecular assemblies observed in the solid state of all four complexes by means of DFT calculations. PMID- 27278812 TI - New Disaccharide-Based Ether Lipids as SK3 Ion Channel Inhibitors. AB - The SK3 potassium channel is involved in the development of bone metastasis and in the settlement of cancer cells in Ca(2+) -rich environments. Ohmline, which is a lactose-based glycero-ether lipid, is a lead compound that decreases SK3 channel activity and consequently limits the migration of SK3-expressing cells. Herein we report the synthesis of three new ohmline analogues in which the connection of the disaccharide moieties (1->6 versus 1->4) and the stereochemistry of the glycosyl linkage was studied. Compound 2 [3-(hexadecyloxy) 2-methoxypropyl-6-O-alpha-d-glucopyranosyl-beta-d-galactopyranoside], which possesses an alpha-glucopyranosyl-(1->6)-beta-galactopyranosyl moiety, was found to decrease SK3 current amplitude (70 % inhibition at 10 MUm), displace SK3 protein outside caveolae, and decrease constitutive Ca(2+) entry (50 % inhibition at 300 nm) and SK3-dependent cell migration (30 % at 300 nm) at a level close to that of the benchmark compound ohmline. Compound 2, which decreases the activity of SK3 channel (but not SK2 channel), is a new drug candidate to reduce cancer cell migration and to prevent bone metastasis. PMID- 27278814 TI - Objective-subjective disparity in cancer-related cognitive impairment: does the use of change measures help reconcile the difference? AB - OBJECTIVE: Studies to date have found little correlation between subjective and objective measures of cognitive function in cancer patients, making it difficult to interpret the significance of their cognitive complaints. The purpose of this study was to determine if a stronger correlation would be obtained using measures of cognitive change rather than static scores. METHODS: Sixty women with early stage breast cancer underwent repeated cognitive assessment over the course of chemotherapy with a neuropsychological test battery (objective measure) and with the FACT-Cog (subjective measure). Their results were compared to 60 healthy women matched on age and education and assessed at similar intervals. We used multilevel modeling, with FACT-Cog as the dependent measure and ordinary least squares slopes of a neuropsychological summary score as the independent variable, to evaluate the co-variation between the subjective and objective measures over time RESULTS: Measures of both objective and subjective cognitive function declined over the course of chemotherapy in the breast cancer patients but there was no significant relationship between them, even when using change measures. Change in objective cognitive function was not related to change in anxiety or fatigue scores but the decline in perceived cognitive function was associated with greater anxiety and fatigue. CONCLUSIONS: The discrepancy in objective and subjective measures of cognition in breast cancer patients cannot be accounted for in terms of a failure to use change measures. Although the results are negative, we contend that this is the more appropriate methodology for analyzing cancer-related changes in cognition. PMID- 27278815 TI - AuDis: an automatic CRF-enhanced disease normalization in biomedical text. AB - Diseases play central roles in many areas of biomedical research and healthcare. Consequently, aggregating the disease knowledge and treatment research reports becomes an extremely critical issue, especially in rapid-growth knowledge bases (e.g. PubMed). We therefore developed a system, AuDis, for disease mention recognition and normalization in biomedical texts. Our system utilizes an order two conditional random fields model. To optimize the results, we customize several post-processing steps, including abbreviation resolution, consistency improvement and stopwords filtering. As the official evaluation on the CDR task in BioCreative V, AuDis obtained the best performance (86.46% of F-score) among 40 runs (16 unique teams) on disease normalization of the DNER sub task. These results suggest that AuDis is a high-performance recognition system for disease recognition and normalization from biomedical literature.Database URL: http://ikmlab.csie.ncku.edu.tw/CDR2015/AuDis.html. PMID- 27278816 TI - SinEx DB: a database for single exon coding sequences in mammalian genomes. AB - Eukaryotic genes are typically interrupted by intragenic, noncoding sequences termed introns. However, some genes lack introns in their coding sequence (CDS) and are generally known as 'single exon genes' (SEGs). In this work, a SEG is defined as a nuclear, protein-coding gene that lacks introns in its CDS. Whereas, many public databases of Eukaryotic multi-exon genes are available, there are only two specialized databases for SEGs. The present work addresses the need for a more extensive and diverse database by creating SinEx DB, a publicly available, searchable database of predicted SEGs from 10 completely sequenced mammalian genomes including human. SinEx DB houses the DNA and protein sequence information of these SEGs and includes their functional predictions (KOG) and the relative distribution of these functions within species. The information is stored in a relational database built with My SQL Server 5.1.33 and the complete dataset of SEG sequences and their functional predictions are available for downloading. SinEx DB can be interrogated by: (i) a browsable phylogenetic schema, (ii) carrying out BLAST searches to the in-house SinEx DB of SEGs and (iii) via an advanced search mode in which the database can be searched by key words and any combination of searches by species and predicted functions. SinEx DB provides a rich source of information for advancing our understanding of the evolution and function of SEGs.Database URL: www.sinex.cl. PMID- 27278817 TI - Mining clinical attributes of genomic variants through assisted literature curation in Egas. AB - The veritable deluge of biological data over recent years has led to the establishment of a considerable number of knowledge resources that compile curated information extracted from the literature and store it in structured form, facilitating its use and exploitation. In this article, we focus on the curation of inherited genetic variants and associated clinical attributes, such as zygosity, penetrance or inheritance mode, and describe the use of Egas for this task. Egas is a web-based platform for text-mining assisted literature curation that focuses on usability through modern design solutions and simple user interactions. Egas offers a flexible and customizable tool that allows defining the concept types and relations of interest for a given annotation task, as well as the ontologies used for normalizing each concept type. Further, annotations may be performed on raw documents or on the results of automated concept identification and relation extraction tools. Users can inspect, correct or remove automatic text-mining results, manually add new annotations, and export the results to standard formats. Egas is compatible with the most recent versions of Google Chrome, Mozilla Firefox, Internet Explorer and Safari and is available for use at https://demo.bmd-software.com/egas/Database URL: https://demo.bmd software.com/egas/. PMID- 27278818 TI - The antineoplastic agent alpha-bisabolol promotes cell death by inducing pores in mitochondria and lysosomes. AB - The sesquiterpene alpha-bisabolol (alpha-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of alpha-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis. The study focuses on the relevant steps in the cytotoxic cascade triggered by alpha-BSB: (1) the lipid rafts through which alpha-BSB enters the cells, (2) the opening of pores in the mitochondria and lysosomes, (3) the activation of both caspase-dependent and caspase-independent cell death pathways, (4) the induction of autophagy and (5) apoptosis. The effectiveness of alpha-BSB as an agent against tumor cells is grounded on its capability to act on different layers of cell regulation to elicit different concurrent death signals, thereby neutralizing a variety of aberrant survival mechanisms leading to treatment resistance in neoplastic cell. PMID- 27278819 TI - Enantioselective direct vinylogous aldol-cyclization cascade reaction between beta,gamma-unsaturated amides and o-quinones. AB - 1,2-Diketones are employed, for the first time, as electrophiles in the vinylogous aldol reaction. With 5 mol% of chiral tertiary amine-thiourea , a direct vinylogous aldol-cyclization cascade reaction between beta,gamma unsaturated amides and o-quinones has been achieved to produce spirocyclic dihydropyranones in 76-99% yield and 82-95% ee. PMID- 27278820 TI - Quercetin inhibits the growth of human gastric cancer stem cells by inducing mitochondrial-dependent apoptosis through the inhibition of PI3K/Akt signaling. AB - Cancer stem cells (CSCs) have recently been linked to new treatment strategies for gastric cancer due to the critical role which they play as the 'heartbeat' of cancer. In the present study, we explored the effects of quercetin, an anti inflammatory and antiviral compound, on gastric CSCs (GCSCs). We noted that quercetin exerted pronounced inhibitory effects on GCSC survival. Moreover, quercetin induced cell apoptosis in a mitochondrial-dependent manner, as shown by the reduction in mitochondrial membrane potential, the activation of caspase-3 and -9, and the downregulation of Bcl-2, as well as the upregulation of Bax and cytochrome c (Cyt-c). Additionally, a marked decrease in Akt phosphorylation levels was observed following treatment with quercetin, whereas pre-treatment with fumonisin B1 (FB1, Akt activator) significantly attenuated the inhibitory effects of quercetin on cell growth and its promoting effects on mitochondrial dependent apoptosis. Notably, FB1 enhanced the expression of Bcl-2, which was inhibited by quercetin, and prevented the decrease in mitochondrial membrane potential induced by quercetin. However, the increase in the levels of caspases, Bax and Cyt-c induced by quercetin was also attenuated by the addition of FB1 to the GCSCs. Therefore, our results demonstrate that quercetin triggers mitochondrial apoptotic-dependent growth inhibition via the blockade of phosphoinositide 3-kinase (PI3K)-Akt signaling in GCSCs, indicating a potential target for the treatment of gastric cancer. PMID- 27278821 TI - Opinions of Nurses About the Evaluation of Risk of Falling Among Inpatients. AB - BACKGROUND: Patient falls and fall-related injuries are an important problem for patients, relatives, caregivers, and the health system at large. AIMS: This study aims to identify opinions of nurses about the risk of falling among patients staying in hospitals. METHOD: This study uses a qualitative descriptive design and employs a semistructured interview method to identify the opinions and experiences of nurses about patient falls. This study evaluated the opinions of a total of 12 staff nurses. FINDINGS: It was found that nurses consider patients in the postoperative period to be most prone to falls. They think that most falls take place during transfers and that the medical diagnosis of the patient plays a crucial role in fall incidents. The most important problem associated with patient falls was symptoms of traumatic brain injury. According to the participating nurses, the risk of fall for every patient should be evaluated upon admission. Measures that the nurses take against patient falls include raising the bed's side rails and securing the bed brakes. CONCLUSIONS: The findings of this research suggest that in-service training programs about the evaluation of the risk of falling should be organized for nurses. Guidelines should be developed for patients with different levels of risk of falling. It is suggested that nurses should be in charge of training patients who are conscious, their relatives, and caregiver personnel. CLINICAL RELEVANCE: The training of nurses and caregivers helps to prevent the falls of inpatients. PMID- 27278823 TI - Potentially Extreme Population Displacement and Concentration in the Tropics Under Non-Extreme Warming. AB - Evidence increasingly suggests that as climate warms, some plant, animal, and human populations may move to preserve their environmental temperature. The distances they must travel to do this depends on how much cooler nearby surfaces temperatures are. Because large-scale atmospheric dynamics constrain surface temperatures to be nearly uniform near the equator, these displacements can grow to extreme distances in the tropics, even under relatively mild warming scenarios. Here we show that in order to preserve their annual mean temperatures, tropical populations would have to travel distances greater than 1000 km over less than a century if global mean temperature rises by 2 degrees C over the same period. The disproportionately rapid evacuation of the tropics under such a scenario would cause migrants to concentrate in tropical margins and the subtropics, where population densities would increase 300% or more. These results may have critical consequences for ecosystem and human wellbeing in tropical contexts where alternatives to geographic displacement are limited. PMID- 27278822 TI - The Parkinson's disease-associated genes ATP13A2 and SYT11 regulate autophagy via a common pathway. AB - Forms of Parkinson's disease (PD) are associated with lysosomal and autophagic dysfunction. ATP13A2, which is mutated in some types of early-onset Parkinsonism, has been suggested as a regulator of the autophagy-lysosome pathway. However, little is known about the ATP13A2 effectors and how they regulate this pathway. Here we show that ATP13A2 depletion negatively regulates another PD-associated gene (SYT11) at both transcriptional and post-translational levels. Decreased SYT11 transcription is controlled by a mechanism dependent on MYCBP2-induced ubiquitination of TSC2, which leads to mTORC1 activation and decreased TFEB mediated transcription of SYT11, while increased protein turnover is regulated by SYT11 ubiquitination and degradation. Both mechanisms account for a decrease in the levels of SYT11, which, in turn, induces lysosomal dysfunction and impaired degradation of autophagosomes. Thus, we propose that ATP13A2 and SYT11 form a new functional network in the regulation of the autophagy-lysosome pathway, which is likely to contribute to forms of PD-associated neurodegeneration. PMID- 27278825 TI - Photo and Collision Induced Isomerization of a Cyclic Retinal Derivative: An Ion Mobility Study. AB - A cationic degradation product, formed in solution from retinal Schiff base (RSB), is examined in the gas phase using ion mobility spectrometry, photoisomerization action spectroscopy, and collision induced dissociation (CID). The degradation product is found to be N-n-butyl-2-(beta-ionylidene)-4 methylpyridinium (BIP) produced through 6pi electrocyclization of RSB followed by protonation and loss of dihydrogen. Ion mobility measurements show that BIP exists as trans and cis isomers that can be interconverted through buffer gas collisions and by exposure to light, with a maximum response at lambda = 420 nm.Graphical Abstract. PMID- 27278824 TI - Ground and Excited-Electronic-State Dissociations of Hydrogen-Rich and Hydrogen Deficient Tyrosine Peptide Cation Radicals. AB - We report a comprehensive study of collision-induced dissociation (CID) and near UV photodissociation (UVPD) of a series of tyrosine-containing peptide cation radicals of the hydrogen-rich and hydrogen-deficient types. Stable, long-lived, hydrogen-rich peptide cation radicals, such as [AAAYR + 2H](+?) and several of its sequence and homology variants, were generated by electron transfer dissociation (ETD) of peptide-crown-ether complexes, and their CID-MS(3) dissociations were found to be dramatically different from those upon ETD of the respective peptide dications. All of the hydrogen-rich peptide cation radicals contained major (77%-94%) fractions of species having radical chromophores created by ETD that underwent photodissociation at 355 nm. Analysis of the CID and UVPD spectra pointed to arginine guanidinium radicals as the major components of the hydrogen-rich peptide cation radical population. Hydrogen-deficient peptide cation radicals were generated by intramolecular electron transfer in Cu(II)(2,2':6',2"-terpyridine) complexes and shown to contain chromophores absorbing at 355 nm and undergoing photodissociation. The CID and UVPD spectra showed major differences in fragmentation for [AAAYR](+?) that diminished as the Tyr residue was moved along the peptide chain. UVPD was found to be superior to CID in localizing Calpha-radical positions in peptide cation radical intermediates. Graphical Abstract ?. PMID- 27278826 TI - Basic-targeted echocardiography for neonatologists: a trainee's perspective. AB - Targeted echocardiography has been promoted by neonatologists in recent years but some aspects of its efficacy remain unexplored. We carried out a survey among trainees of targeted echocardiography courses in order to describe their professional characteristics and abilities. Thirty-eight former trainees were included in the survey. Seventy-six percent were experienced neonatologists and 84% practiced other bedside ultrasound diagnostics. Respondents practiced all major indications of targeted echocardiography, with a variable degree of interaction with available Cardiology services. For all but one indications, less than half of the participants use it independently of a pediatric cardiologist support, with percentages varied between 2% (for use of inhaled nitric oxide) and 53% (to assess myocardial contractility). When planning a standard of education and evaluation of targeted echocardiography, a careful consideration of the profile of the final utilizer is an invaluable piece of information. PMID- 27278827 TI - Comparative pathogenesis of eosinophilic meningitis caused by Angiostrongylus mackerrasae and Angiostrongylus cantonensis in murine and guinea pig models of human infection. AB - This study investigated comparatively the pathogenicity of experimental infection of mice and guinea pigs, with Angiostrongylus mackerrasae and the closely related species A. cantonensis. Time course analyses showed that A. mackerrasae causes eosinophilic meningitis in these hosts, which suggests that the species has the potential to cause meningitis in humans and domestic animals. Both A. mackerrasae and the genetically similar A. cantonensis caused eosinophilic meningitis in mice at two time points of 14 and 21 days post infection (dpi). The brain lesions in mice infected with A. mackerrasae were more granulomatous in nature and the parasites were more likely to appear degenerate compared with lesions caused by A. cantonensis. This may indicate that the mouse immune system eliminates A. mackerrasae infection more effectively. The immunologic responses of mice infected with the two Angiostrongylus species was compared by assessing ex vivo stimulated spleen derived T cells and cytokines including interferon-gamma, interleukin 4 and interleukin 17 on 14 and 21 dpi. The results were similar for mice infected with A. cantonensis and A. mackerrasae. Serum from the infected animals with either A. cantonensis or A. mackerrasae recognized total soluble antigen of A. cantonensis female worms on Western blot. PMID- 27278828 TI - Free-Standing Organic Transistors and Circuits with Sub-Micron Thicknesses. AB - The realization of wearable electronic devices with extremely thin and flexible form factors has been a major technological challenge. While substrates typically limit the thickness of thin-film electronic devices, they are usually necessary for their fabrication and functionality. Here we report on ultra-thin organic transistors and integrated circuits using device components whose substrates that have been removed. The fabricated organic circuits with total device thicknesses down to 350 nm have electrical performance levels close to those fabricated on conventional flexible substrates. Moreover, they exhibit excellent mechanical robustness, whereby their static and dynamic electrical characteristics do not change even under 50% compressive strain. Tests using systematically applied compressive strains reveal that these free-standing organic transistors possess anisotropic mechanical stability, and a strain model for a multilayer stack can be used to describe the strain in this sort of ultra-thin device. These results show the feasibility of ultimate-thin organic electronic devices using free standing constructions. PMID- 27278829 TI - Are you loved by ultrasound? PMID- 27278830 TI - Ultrasonographic findings and natural history of intraductal papillary-mucinous neoplasms of the pancreas. AB - It is clear that the prevalence of malignancy is high in the main-duct type of intraductal papillary-mucinous neoplasm (IPMN). Branch-duct IPMNs include several histologic conditions such as carcinoma, adenoma, and hyperplasia. Intraductal papillary adenocarcinoma and papillary adenoma are characterized by papillary protrusions and thick septum-like structures in dilated ducts as delineated by ultrasonography. A solid mass showing a mixedecho pattern in the pancreatic parenchyma is a characteristic finding of invasive types of IPMN. The international guidelines for the management of branch-duct IPMNs suggest that the appearance of symptoms attributable to the cyst, the presence of intramural nodules, a cyst size greater than 30 mm, and dilation of the main pancreatic duct (>6 mm) are indications for resection. Based on the relationship between the height of a papillary protrusion and the diameter of a cystic dilated branch as well as on histological findings, branch-duct IPMNs with papillary protrusions more than 10 mm in height as shown by imaging should be resected, and it is not adequate to differentiate carcinoma from other lesions based on the diameter of cystic branches alone. A follow-up study on branch-duct IPMNs revealed that most papillary protrusions showed a slow increase in size or development of lateral spread, and that there was no development of cancer with stromal invasion during an average follow-up of 46 months. Therefore, the presence of intramural nodules alone should not be an indication for surgery. Also, patients without papillary protrusions or thick septum-like structures are not immediate candidates for surgery. Invasive adenocarcinoma can develop at a pancreatic site different from the area of interest showing cystic changes, with such invasion possibly being multicentric. Therefore, in patients with branch-duct IPMNs, attention should be paid to the entire pancreas when performing follow-up examinations. PMID- 27278831 TI - Investigation of ultrasound image processing to improve perceptibility of microcalcifications. AB - PURPOSE: This article describes an investigation of the detectability of breast microcalcifications by ultrasound imaging. METHODS: Two kinds of experiments were performed to evaluate the spatial and contrast resolution of microstructures in an agar graphite phantom and to analyze human perception of tiny spots. RESULTS: The results showed that most of the difficulties in finding microstructures were not only due to lower echo levels but also to obstructions in the surrounding texture of the image. Based on these results, a new image processing method was proposed to emphasize microcalcifications in mammary glands. This method utilized statistical analysis of the echo signals and also considered the structural pattern of the mammary gland. Processed images from some clinical cases showed adequate extraction of the microcalcifications with efficient cancellation of the mammary gland structure. CONCLUSION: The results suggested that the perception of microcalcifications could be improved by the proposed method. PMID- 27278832 TI - Wall composition analysis of the human hepatic artery by intravascular ultrasound. AB - PURPOSE: The purpose of this study was to elucidate the wall layer appearance of the human hepatic artery shown by intravascular ultrasound (IVUS). METHODS: We evaluated the wall layer appearance of 57 human hepatic arteries from 36 cadavers. The thickness of the inner high-echoic layer and the second low-echoic layer of the arteries was measured by IVUS, and it was compared with that of the arterial intima and media, respectively. RESULTS: The thickness of the inner high echoic layer was 0.2 +/- 0.1 mm and that of the second low-echoic layer was 0.4 +/- 0.1 mm, on IVUS. However, the histological thickness of the intima was 120 +/ 45 MUm and that of the media was 258 +/- 71 MUm. The media of the hepatic artery correlated significantly with the second low-echoic layer on IVUS (r = 0.62, P < 0.01). The diameter of the vessels measured on IVUS correlated significantly with that of the histological specimens (r = 0.89, P < 0.01). CONCLUSION: From our results, the three layers of the hepatic artery detected with IVUS may correspond to the intima, media, and adventitia, respectively. PMID- 27278833 TI - Longitudinal fractional shortening and its relation to diastolic cardiac function. AB - PURPOSE: Although alterations in longitudinal systolic function have been considered the earliest sign of cardiac damage, the importance of longitudinal fractional shortening (LFS), which reflects left ventricular longitudinal contraction, has not been studied in detail. We introduce a new method of measuring LFS by echocardiography and evaluate its efficiency. METHODS: Our study population consisted of 120 patients with diabetes mellitus (DM), 29 healthy volunteers, and 12 patients with coronary artery disease (CAD). LFS was assessed echocardiographically. Patients with DM underwent conventional echocardiography, assessment of left ventricular diastolic function, and pulsed-wave tissue Doppler study. RESULTS: LFS was 0.07 +/- 0.02 in patients with CAD, 0.16 +/- 0.05 in patients with DM, and 0.26 +/- 0.04 in the normal controls. The three groups differed significantly with respect to the mean LFS values, which were significantly lower in patients with DM than in the normal controls. The ratio of peak diastolic velocities during early filling and atrial contraction (Em/Am) measured on pulsed-wave tissue Doppler images was significantly correlated with LFS (r = 0.37, P < 0.0001). CONCLUSION: LFS is correlated with diastolic cardiac function and is a useful and sensitive index for evaluating long-axis systolic function. PMID- 27278834 TI - Flaming portal vein as a new color Doppler sign of portal gas: report of two cases. AB - Portal gas is relatively rare, and the majority of reported cases have shown it to have a close relation to bowel diseases. At present, portal exploration usually begins with color Doppler sonography, and clinicians now possess a good understanding of color Doppler findings of a wide spectrum of portal abnormalities. However, the color Doppler sign we present in this article has not been reported before. We report two cases of ischemic bowel disease in which B mode ultrasound showed multiple hyperechoic spots moving in the portal vein; the color Doppler appearance was as if the portal vein was on fire (flaming portal vein sign). Knowledge of this simple color Doppler sign helps to improve the diagnostic strategies in patients with portal gas. PMID- 27278835 TI - A symptomatic child with ceftriaxone-associated biliary pseudolithiasis. AB - A 5-year-old boy who had pneumonia was treated in a neighboring hospital. Ceftriaxone was administrated 2 g/day divided into two equal intravenous doses. After 1 week of ceftriaxone therapy, the patient developed abdominal pain. In our hospital, an abdominal sonogram showed a hyperechoic band with postacoustic shadow within the collapsed gallbladder. He was diagnosed with ceftriaxone associated biliary pseudolithiasis, and ceftriaxone therapy was ceased. On the 8th our hospital day, he again complained of right abdominal pain after supper. A sonogram revealed high-amplitude echoes within the gallbladder neck and common bile duct. Furthermore, bile duct dilatation was observed. He was managed conservatively, after which the symptoms were resolved. On the 11th day, a sonogram showed only sludge within the gallbladder, and on the 13th day, he was discharged from our hospital. It is important for sonographers to recognize the possible occurrence of biliary pseudolithiasis in ceftriaxone-treated patients, especially when a high dose is used in children. PMID- 27278836 TI - Left-sided hepatic hydrothorax diagnosed by contrast-enhanced ultrasonography with intraperitoneal injection of Levovist. AB - A 62-year-old Japanese woman was admitted to our hospital with dyspnea. Chest X ray revealed massive pleural effusion on the left side. Contrast-enhanced ultrasonography using Levovist was performed to confirm the transdiaphragmatic passage of ascitic fluid into the pleural cavity. After injection of Levovist into the peritoneal cavity, an enhanced pulsative flow into the pleural cavity was detected. This is the first report of hepatic hydrothorax diagnosed by contrast-enhanced ultrasonography. This method is safe and useful for the diagnosis of hepatic hydrothorax, and it allows observation of the real-time movement of ascitic fluid from the peritoneal cavity to the pleural space and detection of the site of the peritoneopleural communication. PMID- 27278837 TI - Hepatobiliary cystadenocarcinoma with rapid growth: report of a case. AB - We describe a case of histologically proven hepatobiliary cystadenocarcinoma with an emphasis on the longterm clinical course. The patient was a 75-year-old man who had been diagnosed as having a simple hepatic cyst at our hospital and had been followed up by abdominal sonography (US) for about 10 years. However, the lesion subsequently showed a sudden increase in size and a marked change in US findings, i.e., from a benign hepatic cyst to a complete solid lesion. Contrast enhanced US revealed the lesion to be filled with fine vessels. This rapid change led us to strongly suspect a hepatobiliary cystadenocarcinoma and, thus, left lateral segmentectomy was performed. The patient is doing well 6 months after the surgical treatment. PMID- 27278838 TI - Budd-Chiari syndrome due to hepatic vein obstruction without inferior vena cava obstruction. PMID- 27278839 TI - Aneurysm of the left gastric vein in a patient with portal hypertension. PMID- 27278840 TI - Portal vein aneurysm. PMID- 27278841 TI - Concerns about the safety of patient examinations. PMID- 27278842 TI - Nanoporous Structures Similar to Those Reported from Squid Sucker Teeth are also Present in Egg Shells of a Terrestrial Flatworm (Platyhelminthes; Rhabditophora; Geoplanidae) from Hachijojima (Izu Islands, Japan). AB - Shells of the egg cocoon of a terrestrial planarian (Diversibipalium sp.) from Hachijojima were found to be composed of a lattice of parallel nanotubes of ca. 120 nm diameter oriented perpendicular to the shell's surface. The arrangement of the porous proteinaceous tubes closely resembles that has recently been reported from the sucker teeth of squid and to date is the only other example of this kind of structure. Although the array of nanotubes undoubtedly contributes to the stiffness of the shell and helps protecting the embryo, questions such as to how the planary worm produces the array of nanotubes and what exactly their chemical and physical properties are versus those of the squid sucker tooth still remain to be answered. PMID- 27278843 TI - Medical ultrasonics in urology. PMID- 27278844 TI - Contrast-enhanced US of ampullary carcinoma: correlations with pathological findings. AB - PURPOSE: To investigate the utility of contrast-enhanced transabdominal ultrasonography (CEUS) in the diagnosis of ampullary cancer (AC). METHODS: In 12 patients with AC, the presence of tumor enhancement, histological type, amount of connective tissue in cancer, and tumor growth pattern were evaluated. The correlation between the tumor growth pattern and enhancement shape, that between the enhancement pattern and surrounding tissue, and the presence of pancreatic infiltration were evaluated. The depth of cancer invasion was mucosa in five patients, within Oddi's sphincter in four, beyond the duodenum but not to the pancreas in two, and pancreatic invasion less than 5 mm in one. RESULTS: The tumor was enhanced in 11 patients but not in the patient with much connective tissue in the tumor. Enhancement was observed in all patients with the intraluminal papillary or mixed type, but not in those with the periductal invasive type. The enhancement shape was predominantly round or irregular in the intraluminal papillary type and predominantly serrated in the mixed type. The enhancement shape differed among the growth patterns. The normal pancreatic parenchyma around the tumor was enhanced in all patients, and pancreatic infiltration was regarded as absent when there was a continuous unenhanced area between the tumor and pancreatic parenchyma. CONCLUSION: CEUS correlates with pathological findings of ampullary cancer. PMID- 27278845 TI - Sonographic characterization of 271 hepatic hemangiomas with typical appearance on CT imaging. AB - PURPOSE: Hepatic hemangioma is the most frequent benign solid tumor that requires differentiation from hepatic malignancy on ultrasonography. Useful ultrasound findings are therefore required for diagnosis. SUBJECTS AND METHODS: The following factors were investigated for 271 masses diagnosed as hepatic hemangioma by contrast-enhanced computed tomography (CT) in 188 patients: hepatic subsegment location, shape, maximum diameter, internal echo level, hyperechoic rim, posterior echoes, marginal hypoechoic band (halo), lateral shadow, blood flow signal in the central portion of the mass, and underlying liver disease. RESULTS: Hepatic masses were classified by internal echo pattern as homogeneous hyperechoic (35.0%), homogeneous hypoechoic (22.9%), isoechoic (5.2%), mixed hyperechoic (22.1%), or mixed hypoechoic (14.8%) masses. Twelve masses were isoechoic, and could be recognized by the hyperechoic rim. Posterior echo enhancement was present in 66 masses. There were no cases of posterior echo attenuation. A halo was present in six masses, with the underlying condition being fatty infiltrated liver in two masses; a hypoechoic region with a small amount of fat deposit was present around the mass, and this resembled a halo. This finding was termed a "pseudohalo." There were no masses in which a lateral shadow was observed. In terms of blood flow signals in the central portion of the mass, pulsatile flow was present in only one mass. CONCLUSIONS: Important ultrasonographic findings of hepatic hemangioma are characterized as the absence of lateral shadow (100%) and no attenuation of posterior echoes (100%), while the presence of a hyperechoic rim is useful for detecting isoechoic hemangioma. PMID- 27278846 TI - The value of dynamic imaging for standardization of abdominal ultrasonography. AB - PURPOSE: Digital video recording of dynamic images is a potential way to improve the reproducibility of abdominal ultrasonography (US). Static US and dynamic US were compared using contrast-enhanced computed tomography (CE-CT) as a reference standard, and the value of stored video images was verified. METHODS: The subjects were 120 individuals who had undergone CE-CT <=1 month before undergoing US. After static US, dynamic US was carried out according to the Scanning Procedure for Abdominal Ultrasonography described in this paper, and records of 30 separate scans were saved on digital video discs (DVD) as individual video files for interpretation. The findings from static US and dynamic US were compared. RESULTS: With respect to the abdominal US signs covered in this evaluation, dynamic US achieved a detection rate equivalent to or better than that of static US. Detection rates were significantly more frequent on dynamic US for: enlarged hepatic hilum lymph nodes (P < 0.001); gallbladder wall thickness (P < 0.01); cystic lesions of the liver, bright liver, and splenomegaly (P < 0.05). CONCLUSION: Dynamic US is a valuable tool because it enables repeated evaluation of target organs with playback speed adjustment. PMID- 27278847 TI - Phase II clinical study of DD-723 (perflubutane): dose-response study in patients with breast tumors. AB - PURPOSE: We compared the contrast effect of three doses of DD-723 in subjects with breast tumors to determine the recommended dose. We then evaluated differential diagnosis results using plain ultrasonography, contrast-enhanced ultrasonography (plain + enhanced), and contrast-enhanced magnetic resonance imaging (MRI) compared to the pathological diagnosis. METHODS: To evaluate the contrast effect, contrast-enhanced ultrasonic images were independently evaluated in a randomized sequence by three blinded reviewers trained in the evaluation method beforehand. Multiple evaluation results from the three reviewers were used to assess the overall contrast effect. The differential diagnosis was evaluated independently by three blinded reviewers using contrast-enhanced ultrasonic images and contrast-enhanced magnetic resonance images in a randomized sequence; reviewers were also blinded to subject characteristics. Multiple evaluation results from the three reviewers were used to assess the overall differential diagnosis. RESULTS: The recommended dose of DD-723 is an intermediate dose of 0.12 MUL MB/kg. Accuracy, sensitivity, and specificity were improved more in the differential diagnosis by contrast-enhanced ultrasonography than in plain ultrasonography. Accuracy and specificity were better and sensitivity similar compared to contrast-enhanced MRI. CONCLUSIONS: An intermediate dose showed the highest efficacy in terms of overall contrast effect. Contrast-enhanced ultrasonography is safe and useful when used in differential diagnosis. PMID- 27278848 TI - Left ventricular apical and atrial appendage thrombus with hypertrophic cardiomyopathy in sinus rhythm: a case report. AB - A 47-year-old female with a history of untreated hypertension and diabetes mellitus was referred because of a left ventricular echocardiographic mass with congestive heart failure. At the time of admission, she had already had a cardio embolic stroke with loss of recent memory and slight paralysis of the right upper arm. It was difficult to distinguish between thrombus and tumor. However, her clinical condition required surgical resection as soon as possible. We performed cardiac CT to evaluate the coronary arteries and to scan the mass at the left ventricular apex. This CT evaluation revealed another mass at the left atrial appendage. Thus, these two masses were highly suggestive of thrombi. Subemergency surgical resection of the two masses and a part of the myocardium at the left ventricular apex was successfully performed. The pathological results showed that both the mass in the left ventricular apex and the mass in the left atrial appendage were thrombi, and the myocardial disarray confirmed the echocardiographic diagnosis as hypertrophic cardiomyopathy. PMID- 27278849 TI - A case of pyometra treated with endoscopic ultrasound-guided drainage. AB - A 90-year-old woman was admitted to our hospital because of a high-grade fever and appetite loss. On computed tomography scan, a huge cystic lesion about 10 cm in diameter was observed in the pelvic cavity, attached to the vagina and the neck of uterus. Pyometra was strongly suspected; however, a probe could not be inserted into the opening of the uterus because of atrophic changes. Therefore, we decided to perform endoscopic ultrasound (EUS)-guided drainage of the pyometra using the transrectal route. Foul-smelling yellow-brown pus was aspirated. A guide-wire was inserted and a 7 Fr catheter was inserted into the pyometra through an external fistula. We thus completed the treatment of pyometra without surgical resection. PMID- 27278850 TI - A case report of solitary fibrous tumor of the pleura: ultrasound diagnostic features. AB - Solitary fibrous tumor of the pleura is a rarely encountered clinical entity. Although the majority of these neoplasms have a benign course, the malignant form has also been reported. We describe the case of a 57-year-old male smoker with diabetes who was incidentally diagnosed on chest X-ray with a large solitary mass of the left hemithorax. The diagnostic tests included computed tomography, ultrasound, and contrast-enhanced ultrasound. Radical surgical resection was performed and histological examination confirmed a malignant solitary fibrous tumor of the pleura. The novelty of the case is the use of contrast-enhanced ultrasound in the diagnostic workup. PMID- 27278851 TI - To-and-fro waveforms in the left gastric vein in portal hypertension. AB - Unusual to-and-fro waveforms were demonstrated in the left gastric vein on Doppler sonograms in four patients with liver cirrhosis. The patterns of the to and-fro waveforms were diverse in each of the patients: both hepatopetal and hepatofugal flow occurred in a single waveform in case 1, changes in the flow direction with flow interruption were noted in case 2, and changes in flow direction without observation of flow interruption and changes after meals were noted in cases 3 and 4, respectively. These waveforms may represent a transitional phase during the development of a portal systemic shunt in patients with portal hypertension. PMID- 27278852 TI - A case of parathyroid carcinoma accompanied by a brown tumor. PMID- 27278853 TI - Lens-based wavefront sensorless adaptive optics swept source OCT. AB - Optical coherence tomography (OCT) has revolutionized modern ophthalmology, providing depth resolved images of the retinal layers in a system that is suited to a clinical environment. Although the axial resolution of OCT system, which is a function of the light source bandwidth, is sufficient to resolve retinal features at a micrometer scale, the lateral resolution is dependent on the delivery optics and is limited by ocular aberrations. Through the combination of wavefront sensorless adaptive optics and the use of dual deformable transmissive optical elements, we present a compact lens-based OCT system at an imaging wavelength of 1060 nm for high resolution retinal imaging. We utilized a commercially available variable focal length lens to correct for a wide range of defocus commonly found in patient's eyes, and a novel multi-actuator adaptive lens for aberration correction to achieve near diffraction limited imaging performance at the retina. With a parallel processing computational platform, high resolution cross-sectional and en face retinal image acquisition and display was performed in real time. In order to demonstrate the system functionality and clinical utility, we present images of the photoreceptor cone mosaic and other retinal layers acquired in vivo from research subjects. PMID- 27278855 TI - Bayesian coalescent inference reveals high evolutionary rates and diversification of Zika virus populations. AB - Zika virus (ZIKV) is a member of the family Flaviviridae. In 2015, ZIKV triggered an epidemic in Brazil and spread across Latin America. By May of 2016, the World Health Organization warns over spread of ZIKV beyond this region. Detailed studies on the mode of evolution of ZIKV strains are extremely important for our understanding of the emergence and spread of ZIKV populations. In order to gain insight into these matters, a Bayesian coalescent Markov Chain Monte Carlo analysis of complete genome sequences of recently isolated ZIKV strains was performed. The results of these studies revealed a mean rate of evolution of 1.20 * 10(-3) nucleotide substitutions per site per year (s/s/y) for ZIKV strains enrolled in this study. Several variants isolated in China are grouped together with all strains isolated in Latin America. Another genetic group composed exclusively by Chinese strains were also observed, suggesting the co-circulation of different genetic lineages in China. These findings indicate a high level of diversification of ZIKV populations. Strains isolated from microcephaly cases do not share amino acid substitutions, suggesting that other factors besides viral genetic differences may play a role for the proposed pathogenesis caused by ZIKV infection. J. Med. Virol. 88:1672-1676, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27278854 TI - Tracheobronchoscopic Assessment of Exercise-Induced Pulmonary Hemorrhage and Airway Inflammation in Barrel Racing Horses. AB - BACKGROUND: Poor performance is often suspected to be associated with EIPH in barrel racing horses; however, there are no published reports of EIPH for this discipline. The prevalence of EIPH in barrel racing horses is also unknown. OBJECTIVES: This study was performed to determine the prevalence of EIPH and signs of airway inflammation in barrel racing horses under normal racing conditions in Alberta. ANIMALS: About 170 barrel racing horses. METHODS: Observational cross-sectional study. Tracheobronchoscopic examinations were performed at least 30 minutes postrace. Video recordings were scored off-site independently by two observers for EIPH and tracheal mucus accumulation (TMA). Horses with an EIPH score >=2 were not assessed for TMA. Interobserver agreement was calculated by weighted kappa statistics. Run times, environmental variables, and clinical information were also recorded for analysis. RESULTS: 77/170 (45.3%) of horses examined showed evidence of EIPH (grade >= 1). Interobserver agreement was 0.94. 140/141 (99.3%) of horses assessed for TMA showed evidence of tracheal mucus accumulation (grade >= 1) with 104/141 (73.8%) having a TMA score >= 2. Interobserver agreement was 0.73. A weak positive association was found between EIPH scores and average run speed, the presence of cough at rest reported by the riders, increased recovery time, exercise intolerance, and outdoor pattern. CONCLUSIONS AND CLINICAL IMPORTANCE: The high prevalence of EIPH observed in the sampled population indicates that barrel racing induces substantial stress on the lungs. The presence of EIPH did not impact negatively on performance. Factors such as environmental dust and frequent traveling might have contributed to the high prevalence of TMA observed. PMID- 27278856 TI - Reduced anticipation of negative emotional events in alexithymia. AB - Alexithymia is characterized by difficulties in different domains of emotion processing, especially in relation to negative emotions. Nevertheless, its causal mechanisms remain elusive. Reduced anticipation of negative emotional events might be one such mechanism because it enables the individual to prepare to respond effectively to coming events. To test this, changes in skin conductance response (SCR) were recorded during classical fear conditioning in sixty participants with high (HA), medium (MA) and low (LA) levels of alexithymia. Two coloured squares were presented, one was reinforced with a mild electrical stimulation (CS+) while the other was never reinforced (CS-). Critically, despite all groups showing higher SCR to CS+ compared to CS-, SCR to CS+ was lower and extinguished earlier in HA compared to MA and LA. These differences appeared to be attributable neither to differences in the intensity of stimulation received, nor to SCR to the stimulation itself. Groups showed comparable SCR to CS- as well. Therefore, HA exhibited decreased anticipation of the occurrence of a negative emotional event. Disruption of this mechanism may then compromise effective emotion recognition, emotional response and response regulation, which characterise HA, and represent a unifying causal mechanism underlying the difficulties in emotion processing of this group. PMID- 27278857 TI - Environmental changes define ecological limits to species richness and reveal the mode of macroevolutionary competition. AB - Co-dependent geological and climatic changes obscure how species interact in deep time. The interplay between these environmental factors makes it hard to discern whether ecological competition exerts an upper limit on species richness. Here, using the exceptional fossil record of Cenozoic Era macroperforate planktonic foraminifera, we assess the evidence for alternative modes of macroevolutionary competition. Our models support an environmentally dependent macroevolutionary form of contest competition that yields finite upper bounds on species richness. Models of biotic competition assuming unchanging environmental conditions were overwhelmingly rejected. In the best-supported model, temperature affects the per lineage diversification rate, while both temperature and an environmental driver of sediment accumulation defines the upper limit. The support for contest competition implies that incumbency constrains species richness by restricting niche availability, and that the number of macroevolutionary niches varies as a function of environmental changes. PMID- 27278859 TI - Perceptions of dementia and use of services in minority ethnic communities: a scoping exercise. AB - Despite the rapidly ageing population and a predicted sevenfold increase in the prevalence of dementia in minority ethnic communities, people from these communities remain under-represented in specialist dementia services. Leventhal's Model of Self-Regulation suggests perceptions of illness facilitate help-seeking behaviours such as the use of services. This scoping exercise makes use of the model to explore perceptions of dementia in British Indian, African and Caribbean, and East and Central European communities in the United Kingdom. Between August 2013 and April 2014, culturally specific dementia awareness roadshows were attended by people living with dementia, carers and members of the public. During the roadshows, 62 British Indian, 50 African and Caribbean, and 63 East and Central European attenders participated in discussion groups and a dementia knowledge quiz. Thematic and framework analysis were conducted on the discussion group data. Three main themes are presented: Perceptions of dementia, awareness of dementia in the wider family and community, and awareness and use of services. The findings suggest that although groups attributed a biological basis for memory loss, a number of misconceptions prevailed regarding the cause of dementia. Groups also made use of religion, as opposed to medical healthcare services, as a form of personal and treatment control. Seeking help from healthcare services was hindered by lack of awareness of services, and culturally specific barriers such as language. The findings have a number of implications for policy and practice including the development of public health interventions and the need to focus further on reducing barriers to accessing services. PMID- 27278858 TI - Probenecid, an organic anion transporter 1 and 3 inhibitor, increases plasma and brain exposure of N-acetylcysteine. AB - 1. N-acetylcysteine (NAC) is being investigated as an antioxidant for several conditions including traumatic brain injury, but the mechanism by which it crosses membrane barriers is unknown. We have attempted to understand how the transporter inhibitor, probenecid, affects NAC pharmacokinetics and to evaluate the interaction of NAC with transporters. 2. Juvenile Sprague-Dawley rats were administered NAC alone or in combination with probenecid intraperitoneally. Plasma and brain samples were collected serially and NAC concentrations were measured. Transporter studies were conducted with human embryonic kidney-293 cells that overexpress organic anion transporter (OAT)1 or OAT3 and with human multi-drug resistance-associated protein (MRP)1 or MRP4 membrane vesicles. 3. NAC area under the curve was increased in plasma (1.65-fold) and brain (2.41-fold) by probenecid. The apparent plasma clearance was decreased by 65%. Time- and concentration-dependent NAC uptake that was inhibitable by probenecid was observed with OAT1 and OAT3. No uptake of NAC was observed with MRP1 or MRP4. 4. Our results indicate for the first time that NAC is substrate for OAT1 and OAT3 and that probenecid increases NAC plasma and brain exposure in vivo. These data provide insight regarding how NAC crosses biological barriers and suggest a promising therapeutic strategy to increase NAC exposure. PMID- 27278860 TI - Pseudoalteromonas gelatinilytica sp. nov., isolated from surface seawater. AB - Three Gram-stain-negative, rod-shaped bacteria, designated strains NH153T, F-2-11 and M-1-78, were isolated from surface seawater of the South China Sea and the East China Sea. The three isolates were able to grow at 15-45 degrees C (optimum 28-37 degrees C), but no growth occurred at 4 or 50 degrees C. The pH range for growth was pH 5.5-9.5 (optimum pH 7.5-8.5). The isolates required sea salts for growth and growth occurred in the presence of 0-10 % (w/v) NaCl (optimum 3-5 %); no growth occurred in the presence of 12.0, 15.0 or 20.0 % (w/v) NaCl. They were positive for hydrolysis of gelatin and Tween 80. The sole respiratory quinone was ubiquinone-8 (Q-8). The major cellular fatty acids (>10 %) were C16 : 0, C18 : 1omega7c and summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2-OH). The major polar lipid components were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified glycolipid, one unidentified phospholipid and one unidentified lipid. The genomic DNA G+C content of strain NH153T was 41.4 mol%. Based on 16S rRNA gene sequence analysis, the isolates were closely related to the type strain of Pseudoalteromonas shioyasakiensis (98.0 98.6 % sequence similarity). The 16S rRNA gene sequence similarities between the three isolates were 98.8-99.7 %. Phylogenetic analysis indicated that they formed a distinct lineage and clustered with P. shioyasakiensis and Pseudoalteromonas arabiensis. The level of DNA-DNA relatedness among the three isolates was 78.0 85.5 %. Strain NH153T exhibited average nucleotide identity values of 93.4 and 84.2 % with respect to P. shioyasakiensisJCM 18891T and P. arabiensisJCM 17292T, respectively. The genome-to-genome distance analysis revealed that strain NH153T shared 52.4 % DNA relatedness with P. shioyasakiensisJCM 18891T and 28.1 % with P. arabiensisJCM 17292T. On the basis of the phenotypic, genotypic and chemotaxonomic characterizations, as well as phylogenetic inference obtained in this study, strains NH153T, F-2-11 and M-1-78 represent a novel species within the genus Pseudoalteromonas, for which the name Pseudoalteromonasgelatinilytica sp. nov. is proposed. The type strain is NH153T (=CGMCC 1.15370T=DSM 100951T), and F-2-11 (=CGMCC 1.15364=DSM 100953) and M-1-78 (=CGMCC 1.15365=DSM 100952), are additional strains of the species. PMID- 27278861 TI - Soft tissue sarcomas of the distal lower extremities: A single-institutional analysis of the prognostic significance of surgical margins in 120 patients. AB - Soft tissue sarcomas (STS) arising in the distal lower extremities pose a therapeutic challenge due to concerns of functional morbidity. The impact of surgical margins on local recurrence-free survival (LRFS) and overall survival (OS) still remains controversial. The aim of this study was to identify prognostic indicators of survival and functional outcome in patients with STS of the distal lower extremities through a long-term follow-up. Between 1999 and 2014, 120 patients with STS of the foot, ankle and lower leg were treated surgically at our institution. The median follow-up was 6.3 years. The results reveal that the 5-year estimate of the OS rate was 80.0% [95% confidence interval (CI): 69.6-87.1] for the entire series. Surgical margins attained at the resection of the primary tumor did not influence OS significantly [5-year OS: R0 80.5% (69.7-87.9) vs. R1 74.1% (28.9-93.0); P=0.318]. Within the R0 subgroup, negative surgical margin widths <=1 and >1 mm led to similar outcomes, as well as <=5 and >5 mm, respectively. In the multivariate analysis, significant adverse prognostic features included male gender and age >60 years at the time point of primary diagnosis. In conclusion, the data from this study could not underscore the long-term benefit of negative margins achieved at the resection of the primary tumor. Surgical efforts should aim at function-sparing resections when feasible with negative margins. Here, close negative margins seem to be adequate. PMID- 27278862 TI - MAPK pathways are involved in the inhibitory effect of berberine hydrochloride on gastric cancer MGC 803 cell proliferation and IL-8 secretion in vitro and in vivo. AB - Gastric cancer is the second leading cause of cancer-associated mortality worldwide. This investigation aimed to identify whether the mitogen-activated protein kinase (MAPK) signaling pathways are involved in the inhibitory effect of berberine hydrochloride (BER) on MGC 803 cells in vitro and in vivo. BER time- and dose-dependently inhibited proliferation of MGC 803 cells. It also suppressed tumorigenesis in nude mice xenografted with MGC 803 cells. Additionally, BER reduced interleukin-8 (IL-8) secretion in vitro and in vivo. Further investigation demonstrated that inactivation of p38 MAPK, extracellular-signal regulated kinase 1/2 and c-Jun N-terminal kinase by BER contributed to the decreased proliferation and tumorigenesis, and the change in IL-8 expression levels. However, there was no significant synergistic inhibitory effect of combined BER and evodiamine (EVO) treatment on tumorigenesis, and BER reduced the upregulation of IL-8 induced by EVO in vivo. The results of the current study suggested that BER may be an effective and safe drug candidate for treating gastric cancer via modulation of the MAPK signaling pathways. PMID- 27278863 TI - Specificity of Stress-Responsive Transcription Factors Nrf2, ATF4, and AP-1. AB - Cellular stress leads to an upregulation of gene transcription. We asked if there is a specificity in the activation of the stress-responsive transcription factors Nrf2, ATF4, and AP-1/c-Jun, or if activation of these proteins is a redundant cellular answer toward extracellular stressors. Here, we show that oxidative stress, induced by stimulation of the cells with the oxidant arsenite, strongly activated gene transcription via the stress-responsive element (StRE), while phorbol ester or tunicamycin, activators of AP-1/c-Jun or ATF4, respectively, activated AP-1 or nutrient-sensing response element-mediated transcription. Preincubation of the cells with N-acetyl-cysteine or overexpression of thioredoxin selectively attenuated arsenite-induced upregulation of StRE regulated transcription. Expression of either dominant-negative or constitutively active mutants of Nrf2, ATF4, or c-Jun confirmed that distinct transcription units are regulated by these transcription factors. Physiological stimuli involving the activation of either Galphaq-coupled designer receptors or the protein kinases c-Jun N-terminal protein kinase or p38 strongly stimulated transcription via AP-1/c-Jun, with minimal effects on Nrf2 or ATF4-responsive promoters. Thus, activation of transcription by extracellular signaling molecules shows specificity at the level of the chemical nature of the signaling molecule, at the level of the intracellular transduction process, and at the level of signal-responsive transcription factors. J. Cell. Biochem. 118: 127-140, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27278880 TI - Generation of Lung and Airway Epithelial Cells from Embryonic Stem Cells In Vitro. AB - The epithelium covers the internal surface of the lung airways and is composed of numerous cell types that arise from the anterior foregut endoderm. The ability to generate pulmonary cells from embryonic stem cells will allow study of lung development, drug screening, regenerative medicine, and modeling of lung diseases. The aim of this review is to describe the methods used to produce lung cells in vitro, based on mechanisms of lung development in during embryology. PMID- 27278879 TI - Exosome-derived microRNAs contribute to prostate cancer chemoresistance. AB - Certain microRNAs (miRNAs) play a key role in cancer cell chemoresistance. However, the pleiotropic functions of exosome-derived miRNAs on developing chemoresistance remain unknown. In the present study, we aimed to construct potential networks of miRNAs, which derived from the exosome of chemoresistant prostate cancer (PCa) cells, with their known target genes using miRNA expression profiling and bioinformatic tools. Global miRNA expression profiles were measured by microarray. Twelve miRNAs were initially selected and validated by qRT-PCR. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of miRNAs and their targer genes from the selected KEGG pathway 'PCa progression (hsa05215)' were visualized by Cytoscape software. We identified 29 deregulated miRNAs, including 19 upregulated and 10 downregulated, in exosome samples derived from two kinds of paclitaxel resistance PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). The enrichment results of deregulated miRNAs and known target genes showed that a few pathways were correlated with several critical cell signaling pathways. We found that hub hsa-miR3176, -141-3p, -5004-5p, -16-5p, 3915, -488-3p, -23c, -3673 and -3654 were potential targets to hub gene androgen receptor (AR) and phosphatase and tensin homolog (PTEN). Hub gene T-cell factors/lymphoid enhancer-binding factors 4 (TCF4) target genes were mainly regulated by hub hsa-miR-32-5, -141-3p, -606, -381 and -429. These results may provide a linkage between PCa chemoresistance and exosome regulatory networks and thus lead us to propose that AR, PTEN and TCF4 genes may be the important genes which are regulated by exosome miRNAs in chemoresistance cancer cells. PMID- 27278881 TI - Protein Delivery of Thymidylate Kinase Mediated by Tumor-Specific Antibody Precoated Microvesicles. AB - Molecular targeted therapy is an important, novel approach in the treatment of cancer because it interferes with certain molecules involved in carcinogenesis and tumor growth. Examples include monoclonal antibodies, microvesicles, and suicide genes. Several studies have focused on targeted therapies in prostate cancer, which is a serious cause of cancer death in men. We hypothesize that antibody-coated microvesicles can deliver thymidylate kinase, a suicide protein, to prostate cancer cells, potentiating them to death following azidothymidine (AZT) treatment. PMID- 27278882 TI - The Importance of Mutational Drivers in GBM. AB - Glioblastoma (GBM) is the most aggressive primary brain tumor, providing few effective therapeutic options, given the tumor heterogeneity and the accumulation of different genetic abnormalities that cause treatment failure. The many different genetic and epigenetic alterations present in GBM lead to modification of several major signaling pathways resulting in brain tumor growth, progression, and therapeutic resistance. Many functionally important mutations have been discovered, known as neutral passengers. IDH1/2, EZH2, and DNMT3A are the best known epigenetic modifiers in cancer. These mutations are important in determining disease prognosis such that the status of the MGMT gene is a direct target of chemotherapy. For these reasons, newly developed technologies are necessary to determine new candidate targets for targeted-therapy development in GBM. The determination of mutations will aid in this and in the discovery of combinations of targeted and conventional therapies to improve GBM treatment. PMID- 27278884 TI - Human Mesenchymal Stem Cells in Cancer Therapy. AB - Human mesenchymal stem cells (hMSCs) have the ability to differentiate into several tissue types. Their use in cancer therapeutics or as therapeutic delivery vehicles has significant potential, particularly in their exosome/microvesicle mediated tissue regeneration abilities. In this review, the potential use of hMSCs in cancer therapy is discussed. PMID- 27278883 TI - The Route to HPV-Associated Neoplastic Transformation: A Review of the Literature. AB - Human papillomaviruses (HPVs)-small, nonenveloped viruses with double-stranded circular DNA-are believed to have a role in the progression of cancer. However, the exact mechanisms are not well established. The interference of HPV proteins, especially E6 and E7, in the cell cycle is considered to be the main pathway. It is still questioned whether the expression of these proteins or the viral load is more important in neoplastic transformation. Furthermore, HPV is believed to adapt mechanisms to evade the host cell immune system; persistent HPV infection may also play a role in oncogenic transformation by causing genomic instability and local immune suppression. These factors may cause accumulation of genomic alterations within the host cell and integration of the viral genome into the host genome. In recent years, epigenetic modifications, such as methylation, have also been considered to take part in neoplastic transformation. All of these alterations to the genome may be favorable to the development of cancer. This article highlights the association of HPV in neoplastic transformation and cancer progression. PMID- 27278885 TI - Dual Role of p21 in the Progression of Cancer and Its Treatment. AB - Cancer develops due to an imbalance between cell proliferation and cell death. Various mechanisms of carcinogenesis as well as of novel anticancer agents that could be targeted for the treatment of cancer have been proposed by different studies. Among these, p21 is recognized as a potent cyclin-dependent kinase inhibitor that facilitates cell-cycle arrest by interacting with different stimuli such as p53, DNA repair process, CDK, E2F1, MYC, PCNA, STAT3 AP4, proteasomes, K1F, CDX2, and ER-alpha. p21 acts both as a tumor-suppressor gene and an inhibitor of apoptosis by interacting with various molecules and transition factors. In this review, we discuss the complex role of p21 in the development of cancer and as a target in its treatment. We conclude that, in the future, the tumor-suppressor activity of p21 should be the focus of a novel treatment strategies, which may lead to the devolvement of new and selective anti cancer agents for the targeted therapy of cancers. PMID- 27278886 TI - Imaging of DNA and Protein-DNA Complexes with Atomic Force Microscopy. AB - This article reviews atomic force microscopy (AFM) studies of DNA structure and dynamics and protein-DNA complexes, including recent advances in the visualization of protein-DNA complexes with the use of cutting-edge, high-speed AFM. Special emphasis is given to direct nanoscale visualization of dynamics of protein-DNA complexes. In the area of DNA structure and dynamics, structural studies of local non-B conformations of DNA and the interplay of local and global DNA conformations are reviewed. The application of time-lapse AFM nanoscale imaging of DNA dynamics is illustrated by studies of Holliday junction branch migration. Structure and dynamics of protein-DNA interactions include problems related to site-specific DNA recombination, DNA replication, and DNA mismatch repair. Studies involving the structure and dynamics of chromatin are also described. PMID- 27278888 TI - The Journal of Anatomy: origin and evolution. AB - The Journal of Anatomy was launched 150 years ago as the Journal of Anatomy and Physiology, in an age when anatomy and physiology were not regarded as separate disciplines. European science in general was advancing rapidly at the time (it was 7 years after publication of Darwin's Origin of Species), and the recent demise of the Natural History Review meant that there was no English language publication covering these subjects. The founding editors were George Murray Humphry of Cambridge and William Turner of Edinburgh, together with Alfred Newton of Cambridge and Edward Perceval Wright of Dublin (the last two served only for a year). The pivotal event leading to the Journal's foundation was the 1866 meeting of the British Association, at which Humphry delivered the 'Address in Physiology' (printed in the first issue). Turner, who was also present at the 1866 British Association meeting, remained as a member of the editorial team for 50 years and was a major contributor of Journal articles. The title was changed to Journal of Anatomy in October 1916, when it was taken under the wing, in terms of both management and ownership, by the Anatomical Society. This article reviews the early years of the Journal's publication in more detail than later years because of the historical interest of this less familiar material. The subject matter, which has remained surprisingly consistent over the years, is illustrated by examples from some notable contributions. The evolution of illustration techniques is surveyed from 1866 to the present day; the final section provides brief summaries of all of the chief editors. PMID- 27278890 TI - Functional bone histology of zebrafish reveals two types of endochondral ossification, different types of osteoblast clusters and a new bone type. AB - The zebrafish is as an important vertebrate animal model system for studying developmental processes, gene functions and signalling pathways. It is also used as a model system for the understanding of human developmental diseases including those related to the skeleton. However, surprisingly little is known about normal zebrafish skeletogenesis and osteogenesis. As in most vertebrates, it is commonly known that the bones of adult zebrafish are cellular unlike that of some other teleosts. After careful histological analyses of each zebrafish adult bone, we identified several acellular bones, with no entrapped osteocytes in addition to several cellular bones. We show that both cellular and acellular bones can even occur within the same skeletal element and transitions between these two cell types can be found. Furthermore, we describe two types of osteoblast clusters during skeletogenesis and two different types of endochondral ossification. The epiphyseal plate, for example, lacks a zone of calcification and a degradation zone with osteoblasts. A new bone type that we term tubular bone was also identified. This bone is completely filled with adipose tissue, unlike spongy bones. This study provides important insight on how osteogenesis takes place in zebrafish, and especially on the transition from cellular to acellular bones. Overall, this study leads to a deeper understanding of the functional histological composition of adult zebrafish bones. PMID- 27278892 TI - AFSUMB 2004: a group undertaking. PMID- 27278889 TI - A brief history of topographical anatomy. AB - This brief history of topographical anatomy begins with Egyptian medical papyri and the works known collectively as the Greco-Arabian canon, the time line then moves on to the excitement of discovery that characterised the Renaissance, the increasing regulatory and legislative frameworks introduced in the 18th and 19th centuries, and ends with a consideration of the impact of technology that epitomises the period from the late 19th century to the present day. This paper is based on a lecture I gave at the Winter Meeting of the Anatomical Society in Cambridge in December 2015, when I was awarded the Anatomical Society Medal. PMID- 27278893 TI - A novel treatment for early gastrointestinal carcinoma by ultrasonic endoscopic mucosal stripping. AB - PURPOSE: The aim of this study was to clarify the indications for a new endoscopic mucosal resection (EMR) technique that employs a cavitational ultrasonic surgical aspirator (CUSA). Endoscopic mucosal resection has proved an effective technique for treating early mucosal gastrointestinal cancer. However, resecting a lesion larger than 2 cm en bloc requires special devices and a long processing time; and it engenders the risk of bleeding, perforation, and other complications. METHODS: We investigated application of the CUSA for detaching the mucosa from the muscularis propria of extracted porcine stomachs and then clarified the specification of an endoscopic ultrasonic scalpel for endoscopic mucosal resection by investigating characteristics of two original, handmade prototype cavitational ultrasonic surgical aspirators. RESULTS: Use of a cavitational ultrasonic surgical aspirator should improve the ease and safety of detaching the mucosa. A small, high-power ultrasonic cylindrical vibrator should be developed to make possible a probe-type scalpel with a piezoelectric vibrator mounted in the tip of a catheter. An ultrasonic transmission-type scalpel could lead to the development of a new endoscopic mucosal resection device for clinical use. CONCLUSIONS: The CUSA should enable us to develop a safer, simpler, time saving scalpel for endoscopic mucosal resection, although some resolvable technical problems remain. The CUSA might enable us to diagnose carcinoma invasion into the submucosa in aspirated specimens and then aspirate out the entire invading submucosal carcinoma. PMID- 27278891 TI - Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation. AB - Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd(2+) bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K(+) coordination, a hallmark for C-type inactivation. An engineered Cd(2+) bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel. PMID- 27278894 TI - Questionnaire survey on the state of routine echocardiographic examinations in Japan: second report. AB - We mailed questionnaires to 748 registered medical sonographers [RMSs (cardiology)] to gather information for a large-scale survey of RMSs in May 2000. We wanted to evaluate the current state of routine echocardiography in Japan. Altogether, 530 (70.9%) of these sonographers responded; 18 respondents employed by equipment manufacturers were excluded from the start of the study, and 20 others later found to be employed by equipment manufacturers were also excluded. Responses from all personnel at a single institution were treated as a single response; 436 institutions were thus included in the survey. Most or all examinations were carried out by sonographers at 77.3% of the responding institutions but were performed mainly by physicians at 11.1% of the institutions. At least 80% of sonographer or physician working hours were used for echocardiographic examination at 18.9% of the surveyed institutions, whereas up to half the working hours were devoted to echocardiographic examinations at 67.0% of the institutions. The most frequently reported examination time was 30 40 min [35.6% (n = 116) of the institutions], whereas 32.8% (n = 107) of the institutions indicated durations of 10-20 min per examination. Left ventricular (LV) dimensions and wall thickness were measured on M-mode images in all patients at 14.1% (n = 59) of the institutions and mainly on M-mode images but from two dimensional echocardiography in problematic patients at 74.2% (n = 311) of the institutions. The LV ejection fraction was calculated from LV dimensions at 55.7% (n = 205) of the institutions and from the LV cross-sectional area at 44.3% (n = 163) of the institutions. The LV ejection fraction was estimated visually at 57.0% of the institutions. Only 5.5% (n = 22) of the facilities always scored the wall motion. Pulsed Doppler echocardiography was used to assess LV inflow in all patients at 65.9% of the institutions; regurgitation and shunting were always assessed quantitatively at only 2% (n = 8). Comments concerning image quality were reported in all cases or in cases of poor image quality at 98% of the institutions, and the sonographer was also involved in writing the diagnostic report at 94% of institutions. Echocardiography is less expensive than other diagnostic imaging methods, and its importance is thus likely to continue to increase. Echocardiographic examinations should be carried out by skilled RMSs and physician echocardiographers; and an accurate, readily comprehensible report of the findings should be provided promptly to the referring physician. More such surveys are required to ensure that these practices are adopted. PMID- 27278895 TI - Clinical course of acute hemorrhagic infarction of a thyroid nodule. AB - A 27-year-old woman patient with acute hemorrhagic infarction of a thyroid nodule had experienced abrupt painful swelling of the thyroid gland soon after being involved in an automobile accident. We diagnosed her thyroid mass, based on clinical symptoms and laboratory findings, as acute hemorrhagic infarction of a thyroid nodule. The mass diameter gradually decreased from 4.4 cm to 1.9 cm over the following 12 months but did not change thereafter. The serum thyroglobulin level rapidly decreased from 312.4 ng/ml to 14.2 ng/ml during the first 3 months and presented no change during the next 21 months. Fine-needle aspiration biopsy was repeated during the 24th month, when preexistence of a benign neoplasm had become clear. The clinical course of acute hemorrhagic infarction of the thyroid nodule was made apparent by ultrasonography, which readily identified the thyroid mass and accurately measured its dimensions at any time. PMID- 27278896 TI - The Seventh Congress of the Asian Federation of Societies for Ultrasound in Medicine and Biology and the 77th Annual Scientific Meeting of the Japan Society of Ultrasonics in Medicine. PMID- 27278897 TI - Heterogeneous nuclear ribonucleoprotein K is overexpressed and associated with poor prognosis in gastric cancer. AB - Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is one of the major pre-mRNA binding proteins, that is involved in translational modifications. In our previous studies, we found that hnRNP K is associated with human gastric cancer. The protein levels of hnRNP K were detected in cell lines and tissue microarrays. The correlation between hnRNP K expression and patient survival rate was evaluated by Kaplan-Meier survival analysis. In addition, we also detected hnRNP K expression in preoperative and postoperative serum samples from patients with gastric cancer, and serum samples from healthy volunteers. We found that hnRNP K was overexpressed in the gastric cancer cell lines. The levels of hnRNP K were significantly elevated in the gastric cancer tissues compared with that noted in the tumor-adjacent gastric mucosal and normal gastric mucosal sampes, and hnRNP K expression was found to correlate with tumor stage and lymph node metastasis. However, the level of serum hnRNP K did not differ significantly between gastric cancer patients and healthy volunteers. We also found that patients whose tumors showed elevated expression of hnRNP K had poor survival. The present study suggests that hnRNP K is a promising tissue biomarker for diagnosing gastric cancer and is a prognostic indicator for patients with gastric cancer. PMID- 27278898 TI - Pharmacodynamics and differential activity of nitrofurantoin against ESBL positive pathogens involved in urinary tract infections. AB - BACKGROUND: Although nitrofurantoin has been used for >60 years for the treatment of uncomplicated urinary tract infections, its pharmacodynamic properties are not fully explored. Use is increasing because of increasing resistance to other antimicrobials due to ESBLs. METHODS: We tested nine ESBL+ and two ESBL- strains in time-kill assays. Bactericidal activity and regrowth were assessed for all species and concentrations. Early-phase pharmacodynamics was analysed with a sigmoidal Emax model and the maximal killing rate, slope and EC50/MIC ratio were determined for each species. RESULTS: A bactericidal effect was found at >=2* MIC for Enterobacter cloacae after 4-8 h, for Klebsiella pneumoniae after 8-10 h and for Escherichia coli after 12-16 h. Overall, no killing was observed at low sub MIC concentrations, whereas regrowth was found at 0.5-1* MIC after a short decline in cfu. The lowest maximal killing rates were observed for E. coli (0.21 +/- 0.05 h(-1)), followed by K. pneumoniae (0.37 +/- 0.09 h(-1)) and E. cloacae (0.87 +/- 0.01 h(-1)). Surprisingly, the Hill slopes for these three species were significantly different (10.45 +/- 9.37, 2.68 +/- 0.64 and 1.01 +/- 0.06, respectively), indicating a strong concentration-dependent early-phase antibacterial activity against E. cloacae. EC50/MIC ratios were significantly lower for E. coli (0.24 +/- 0.08 mg/L) and K. pneumoniae (0.27 +/- 0.03 mg/L) as compared with E. cloacae (0.77 +/- 0.18 mg/L). CONCLUSIONS: Nitrofurantoin was bactericidal against all species, demonstrating an unusual differential pattern of activity with concentration-dependent-type killing behaviour against E. cloacae and time-dependent killing behaviour against E. coli, which may have significant consequences on species-dependent dosing regimens. The results also demonstrate that the pharmacodynamic properties of some drugs cannot be generalized within a family, here the Enterobacteriaceae. PMID- 27278899 TI - Heterogeneous oxacillin-resistant phenotypes and production of PBP2A by oxacillin susceptible/mecA-positive MRSA strains from Africa. AB - OBJECTIVES: Recent surveillance of MRSA colonizing patients and healthcare workers in two African countries (Angola and Sao Tome and Principe) reported the frequent recovery of oxacillin-susceptible MRSA (OS-MRSA): Staphylococcus aureus strains that gave positive results with the mecA DNA probe, but had low oxacillin MIC values characteristic of susceptible S. aureus. This apparent dissociation of the drug-resistant phenotype from mecA-the primary genetic determinant of resistance-prompted us to perform a more detailed analysis on nine of the African OS-MRSA strains. METHODS: Oxacillin MIC values were determined by Etest and population analysis profiles with and without induction of the stringent stress response by mupirocin. Biochemical profiling using SDS-PAGE followed by western blotting was used for the detection of PBP2A protein produced. RESULTS: Cultures of the African MRSA strains (ST88-IVa and ST8-V) showed heterogeneous oxacillin resistance in which the majority of cells exhibited low oxacillin MICs (<=0.75 mg/L), but highly resistant subpopulations were also present with oxacillin MIC values up to several hundred mg/L and with frequencies of 10(-4) to 10(-6). The same strains after induction of the stringent stress response by mupirocin 'converted' the heterogeneous phenotypes into a more homogeneous and higher level resistance. After induction by oxacillin and mupirocin, each of the nine African OS-MRSA strains produced PBP2A-the protein product of mecA. CONCLUSIONS: The resistant phenotype of OS-MRSA resembles the phenotypes of historically early MRSA clones. The nature of genetic determinants responsible for the heterogeneous phenotypes of OS-MRSA remains to be determined. PMID- 27278900 TI - Gram-negative prosthetic joint infections managed according to a multidisciplinary standardized approach: risk factors for failure and outcome with and without fluoroquinolones. AB - OBJECTIVES: To describe the outcome and risk factors for treatment failure of 76 Gram-negative bacilli (GNB) prosthetic joint infections (PJIs) managed with a curative intent according to a standardized protocol derived from published guidelines. METHODS: We analysed data from all the cases of GNB-PJI treated surgically over an 8 year period. Treatment failure was defined as persistence or recurrence of PJI signs during follow-up, resulting in additional surgery and/or antibiotic administration or death. RESULTS: Treatment failure within the follow up period (median = 2.6 years) was observed in 16 of 76 (21.1%) patients. The failure rate was similar whether the patients were treated with fluoroquinolones in the whole cohort (22.4% versus 16.7%, P = 0.75) and after stratification according to the surgical procedure. The low failure rate observed in patients not receiving fluoroquinolones might be explained by the standardized attitude of maintaining intravenous beta-lactams throughout treatment duration (median = 90 days). In multivariate analysis, C-reactive protein level >=175 mg/L was significantly associated with treatment failure (adjusted HR = 7.75, 95% CI = 2.66-22.59, P < 0.0001). CONCLUSIONS: Management according to standardized procedures may improve the prognosis of GNB-PJI. Intravenous beta-lactams, continued for 3 months, should be considered an effective alternative to fluoroquinolones. PMID- 27278901 TI - Effect of Internal Electric Fields on Charge Carrier Dynamics in a Ferroelectric Material for Solar Energy Conversion. AB - Spontaneous polarization is shown to enhance the lifetimes of photogenerated species in BaTiO3 . This is attributed to polarization-induced surface band bending acting as a thermal barrier to electron/hole recombination. The study indicates that the efficiencies of solar cells and solar fuels devices can be enhanced by the use of ferroelectric materials. PMID- 27278902 TI - Going smoke-free: attitudes of mental health professionals to policy change. AB - WHAT IS KNOWN ON THE SUBJECT?: While smoking rates within the general population in Australia are dropping, 32% of Australians with a mental illness smoke, increasing to 73% among those with severe or chronic mental illness. In Australia and elsewhere, smoking bans within mental health facilities have been implemented. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: We surveyed 98 mental health professionals in Australia to gather information on attitudes toward smoke free policies in mental health/psychiatric units within Australia. While previous research has sought information on agreement or disagreement with smoking-bans, very little research has been conducted focusing on attitudes held by mental health professionals towards smoke-free policies. This study utilized a mixed methods approach in which the qualitative data provides a rich source of information to assist in developing programmes or interventions to influence attitudes and therefore change behaviours of mental health professionals. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This paper can be useful in providing a better understanding of the theories linking smoking and mental illness, and the common 'myths' which influence attitudes to smoking cessation in clinical populations. Results will influence the development of training and education resources for mental health practitioners, and particularly for nursing staff working within psychiatric facilities, in relation to smoking cessation. Importantly, this issue has implications in the areas of policy planning and development, education relating to smoking behaviour and smoking cessation programmes, together with holistic health care. ABSTRACT: Introduction Mental health units in Australia and internationally are increasingly implementing smoke free policies. Due to the high prevalence of smoking among clinical populations, this has become an important research area. Purpose of study This study explored the attitudes of mental health professionals toward smoke-free policies in mental health units within Australia. Method Using an online survey design, 98 Australian mental health professionals participated in the study. Results Results indicated that only 25.5% agreed with a total smoking ban. Although supporting smoke-free initiatives within the wider community, participants commonly held attitudes that were unsupportive of smoking bans, and indicated beliefs inconsistent with a smoke-free policy for clinical populations. Discussion Results suggest the need for appropriate staff education and training regarding smoking behaviours and risks, and smoking cessation treatments for clinical populations if smoke-free policies are to be successfully implemented. Implications for practice Findings suggest important implications for holistic mental health care, staff education and training, as well as policy, planning and development, particularly in relation to this treatment group, who are likely to have entered a psychiatric unit in crisis. PMID- 27278904 TI - A new approach to analyze the dynamic strength of eggs. AB - The mechanical behavior of eggshell was determined in terms of average rupture force and corresponding deformation. For the experiment, we selected goose eggs (Anser anser f. domestica). Samples of eggs were compressed along their x-axis and z-axis. The effect of the loading orientation can be described in terms of the eggshell contour curvature. Two different experimental methods were used: compression between two plates (loading rates up to 5 mm/s) and the Hopkinson split pressure bar technique. This second method enables achieving loading rates up to about 17 m/s. The response of goose eggs to this high loading rate was characterized also by simultaneous measurement of the eggshell surface displacements using a laser vibrometer and by the measurement of both circumferential and meridian strains. PMID- 27278903 TI - Leptospiral outer membrane protein LipL32 induces inflammation and kidney injury in zebrafish larvae. AB - Leptospirosis is an often overlooked cause of acute kidney injury that can lead to multiple organ failure and even death. The principle protein that conserved in many pathogenic leptospires is the outer membrane protein LipL32. However, the role of LipL32 in the pathogenesis of renal injury in leptospirosis is not entirely clear. Here we studied the effects of LipL32 on the developing kidney in zebrafish larvae. Incubation of zebrafish larvae with Leptospira santarosai serovar Shermani induced acute tubular injury predominantly in the proximal pronephric ducts. Furthermore, microinjection of lipl32 mRNA or recombinant LipL32 protein into zebrafish larvae increased macrophage accumulation and disrupted the basolateral location of NA-K-ATPase in pronephric ducts. These changes led to substantial impairment of the pronephric kidney structure. We further demonstrated that morpholino knockdown of tlr2, but not tlr4, reduced the LipL32-induced leukocyte infiltration and kidney injury. These data demonstrate that LipL32 contributes to the renal pathology in leptospirosis and gives some clues to the potential virulence of LipL32. Our results support the use of zebrafish as a model organism for studying the disease mechanism of leptospiral infection. This model might permit the future exploration of the virulence and molecular pathways of different leptospiral outer membrane proteins. PMID- 27278905 TI - Mediators of Atherosclerosis in South Asians Living in America: Use of Web-Based Methods for Follow-Up and Collection of Patient-Reported Outcome Measures. AB - BACKGROUND: A key challenge for longitudinal cohort studies is follow-up and retention of study participants. Participant follow-up in longitudinal cohort studies is costly and time-consuming for research staff and participants. OBJECTIVE: This study determined the feasibility and costs of using Web-based technologies for follow-up and collection of patient-reported outcomes in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. METHODS: The MASALA study is a community-based cohort of 906 South Asians in the United States. Since the baseline in-person visits (2010-2013), a yearly telephone follow-up survey was used to assess participants' health status and incidence of cardiovascular disease. A Web-based version of the follow-up survey was developed using the REDCap (Research Electronic Data Capture) Web app. Participants from the Chicago field center who were due for their annual follow up and who had a valid email address were sent an email link to a secure online portal where they could complete the survey. Telephone follow-up was used with nonresponders. RESULTS: A link to the Web survey was emailed to 285 participants (February to October 2014) and the overall completion rate was 47.7% (136/285). One-third of participants who were unresponsive (n=36) to annual telephone follow up completed the Web survey. Web responders were younger, more likely to be married, and to have higher education and income compared (P<.05) to telephone only responders. Web survey development involved 240 hours of research staff time. Since launching, the Web-based survey has required 3 hours per week of staff time. CONCLUSIONS: Although electronic follow-up will not be a panacea for cohort operations, it will serve as an adjunctive strategy to telephonic follow up for maximizing cohort retention with lower costs. PMID- 27278906 TI - Icariin promotes cell proliferation and regulates gene expression in human neural stem cells in vitro. AB - Icariin (ICA), which is an essential bioactive component extracted from the herb Epimedium, possesses neuroprotective properties. The aim of the present study was to investigate the regulatory roles of ICA in cell proliferation and gene expression in human neural stem cells (NSCs) in vitro. Single cells were isolated from the corpus striatum of 16-20-week human fetuses obtained following spontaneous abortion. The cells were cultured in Dulbecco's modified Eagle's medium/F12 complete medium and were characterized by immunostaining and cell differentiation assay. NSCs were treated with ICA, and cell proliferation was assessed using the Cell Counting kit-8 cell proliferation assay kit. In addition, neurosphere formation was comparatively studied between the ICA-treated and control cells. cDNA microarray analysis was performed to examine the effects of ICA on gene expression. Altered expression of genes important for regulating NSC proliferation was further analyzed by quantitative polymerase chain reaction (qPCR). The results demonstrated that typical neurospheres appeared after 7-10 days of culturing of individual cells isolated from the corpus striatum. These cells expressed nestin, an important NSC marker, and in the presence of differentiation medium they expressed beta-III-tubulin, a specific neuronal marker, and glial fibrillary acidic protein, an astrocyte marker. Treatment with ICA enhanced NSC proliferation and the formation of neurospheres. Microarray data and pathway analysis revealed that the genes regulated by ICA were involved in several signaling pathways, including the Wnt and basic fibroblast growth factor (bFGF) pathways, which are important for the regulation of NSC function. Upregulation of frizzled class receptor 7 and dishevelled segment polarity protein 3, which are key players in the Wnt pathway, and fibroblast growth factor receptor 1, which is the receptor for bFGF, and downregulation of glycogen synthase kinase-3beta, which is a Wnt pathway inhibitor, was further validated by qPCR. In conclusion, ICA promoted proliferation and regulated gene expression in human NSCs, thus suggesting that ICA may exert its neuroprotective effects by regulating NSC activity. PMID- 27278907 TI - [Diagnosis of dental erosions]. PMID- 27278908 TI - Evaluation of the GastroPlusTM Advanced Compartmental and Transit (ACAT) Model in Early Discovery. AB - PURPOSE: The aim of this study was to evaluate the oral exposure predictions obtained early in drug discovery with a generic GastroPlus Advanced Compartmental And Transit (ACAT) model based on the in vivo intravenous blood concentration time profile, in silico properties (lipophilicity, pKa) and in vitro high throughput absorption-distribution-metabolism-excretion (ADME) data (as determined by PAMPA, solubility, liver microsomal stability assays). METHODS: The model was applied to a total of 623 discovery molecules and their oral exposure was predicted in rats and/or dogs. The predictions of Cmax, AUClast and Tmax were compared against the observations. RESULTS: The generic model proved to make predictions of oral Cmax, AUClast and Tmax within 3-fold of the observations for rats in respectively 65%, 68% and 57% of the 537 cases. For dogs, it was respectively 77%, 79% and 85% of the 124 cases. Statistically, the model was most successful at predicting oral exposure of Biopharmaceutical Classification System (BCS) class 1 compounds compared to classes 2 and 3, and was worst at predicting class 4 compounds oral exposure. CONCLUSION: The generic GastroPlus ACAT model provided reasonable predictions especially for BCS class 1 compounds. For compounds of other classes, the model may be refined by obtaining more information on solubility and permeability in secondary assays. This increases confidence that such a model can be used in discovery projects to understand the parameters limiting absorption and extrapolate predictions across species. Also, when predictions disagree with the observations, the model can be updated to test hypotheses and understand oral absorption. PMID- 27278909 TI - A new report of Nocardiopsis valliformis strain OT1 from alkaline Lonar crater of India and its use in synthesis of silver nanoparticles with special reference to evaluation of antibacterial activity and cytotoxicity. AB - The authors report the biological synthesis of silver nanoparticles (AgNPs) by alkaliphilic actinobacterium Nocardiopsis valliformis OT1 strain isolated for the first time from Lonar crater, India. The primary detection of silver NPs formation was made by colour change from colourless to dark brown and confirmed by UV-Vis spectrum of AgNPs at 423 nm, specific for AgNPs. Further, AgNPs were characterized by nanoparticle tracking analysis, Zeta sizer, Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM) analyses. FTIR analysis showed the presence of proteins as capping agent. TEM analysis revealed the formation of spherical and polydispersed AgNPs within the size range of 5-50 nm. The antimicrobial activity of silver nanoparticles against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis was evaluated. The AgNPs showed the maximum antibacterial activity against B. subtilis (Gram positive) and the minimum against E. coli (Gram negative). The minimal inhibitory concentration values of AgNPs for the tested bacteria were found to be in the range of 30-80 ug/mL. The AgNPs demonstrated higher antibacterial activity against all the bacteria tested as compared with the commercially available antibiotics. The cytotoxicity of biosynthesized AgNPs against in vitro human cervical cancer cell line (HeLa) demonstrated a dose-response activity. The IC50 value was found to be 100 ug/mL of AgNPs against cancer HeLa cell line. PMID- 27278910 TI - Three-dimensional echocardiography: a new paradigm shift. AB - Significant advances in three-dimensional echocardiography (3DE) have made this modality a powerful diagnostic tool in the cardiology clinic. It can provide accurate and reliable measurements of chamber size and function. In addition, 3DE offers novel views and comprehensive anatomic definition of valvular and congenital abnormalities by rendering 3D contoured images of the structures. It is also useful in monitoring the effectiveness of surgical or percutaneous transcatheter interventions. With demonstrations of efficacy in various clinical settings, 3DE has become a complementary part of the routine diagnostic armamentarium. However, 3DE is regarded as simply a tool for 3D volume or image rendering. If we confine the role of 3DE to this, it will remain a complementary tool to two-dimensional echocardiography (2DE) in the future. Three-dimensional echocardiography has roles beyond 3D volume or image rendering. Three-dimensional echocardiography can acquire a full volume dataset in a single shot, and with combined use of the multiplanar reconstructive mode, it can provide anatomically well-defined 2D planes from the full volume dataset. Hence, by omitting routine 2DE work, 3DE may save time for image acquisition and allow more precise and reproducible review or measurement. Taking this perspective into account, 3DE can be a suitable modality for use as a substitute for 2DE in daily practice. With further advances of 3DE and development of a unified review system capable of display and geometrical assessment of 2D as well as 3D images, 3DE will represent a new paradigm shift in echocardiographic examination in the future. PMID- 27278911 TI - Low-flow aortic stenosis and preserved left ventricular ejection fraction. AB - Valvular aortic stenosis (AS) is the most frequent valvular disease in developed countries. Treatment decisions in AS are mainly based upon the symptomatic status of the patient and the severity of AS. Doppler echocardiography represents the standard tool for detecting and assessing the severity of the disease. Under the same denomination of severe AS [aortic valve area (AVA) < 1 cm(2)], several entities might be identified that differ in terms of trans-valvular flow rates and pressure gradients development. From a clinical standpoint, severe AS (AVA < 1 cm(2)) can be subdivided into 4 flow-gradient patterns: normal flow/low gradient (NF/LG), normal flow/high gradient (NF/HG), low flow/high gradient (LF/HG) and low flow/low gradient (LF/LG). The most commonly described entity is the paradoxical low-flow, low-gradient severe AS state, in which the stroke volume is unexpectedly reduced, despite preserved left ventricular (LV) ejection fraction. In daily practice, misdiagnosing this clinical condition might lead to an inappropriate timing of follow-up with an unnecessary delay of aortic valve replacement (AVR), which may, in turn, have a negative impact on patient outcome. PMID- 27278912 TI - Predictors of improvement in diastolic function after transcatheter aortic valve implantation. AB - BACKGROUND: Aortic stenosis is associated with concentric left ventricle (LV) hypertrophy or remodeling resulting in impaired diastolic function and elevated left-sided filling pressure. We investigated the changes in LV geometry and LV filling hemodynamics, giving emphasis to parameters associated with changes in diastolic function after transcatheter aortic valve implantation (TAVI). METHODS: Comprehensive diastolic assessment was performed before and six months after TAVI in 70 patients with severe aortic stenosis. Patients with any degree of mitral stenosis or >mild left-sided valvular regurgitation were excluded. RESULTS: In the entire cohort six months after TAVI, LV end-diastolic diameter increased (44.1 +/- 6 versus 45 +/- 6 mm, P = 0.02), whereas LV mass and relative wall thickness (RWT) decreased (270.1 +/- 76 versus 245.1 +/- 75 g and 0.53 +/- 0.15 versus 0.46 +/- 0.1, respectively; P < 0.0001 for both). Lateral e' increased (5.8 +/- 2 versus 6.6 +/- 3 cm/s, P = 0.03) and left atrium (LA) volume, E/e' ratio, and systolic pulmonary pressure decreased (88.1 +/- 30 versus 80 +/- 28 cc, 18 +/- 7.8 versus 16.3 +/- 5.5, and 42.7 +/- 14.9 versus 38.7 +/- 12 mmHg, respectively; P < 0.05 for all), suggesting reduction in LA pressure. The improvement in LA volume and E/e' was almost exclusively seen in patients with LV hypertrophy before TAVI (P < 0.05 both), as opposed to patients with concentric remodeling. CONCLUSIONS: In our preliminary study, TAVI resulted in LV and LA reverse remodeling, and improved LV relaxation and LA filling pressure in patients with severe aortic stenosis and concentric hypertrophy. Patients with concentric remodeling at baseline seem to have limited improvement in LV diastolic function and filling pressure following TAVI, but larger clinical trials would be required to conclude if they have no improvement at all. PMID- 27278913 TI - Assessment of the aortic valve annular geometry by real-time three-dimensional transthoracic echocardiography: comparison with two-dimensional transthoracic echocardiography and multidetector computed tomography. AB - BACKGROUND: Real-time three-dimensional transthoracic echocardiography (3DTTE) has been developed and provides detailed 3D information, noninvasively. However, the accuracy and usefulness of 3DTTE in the evaluation of aortic root geometry are still not clear. METHODS: 2DTTE and 3DTTE were performed in 161 patients with various cardiac diseases. Multidetector computed tomography (MDCT) was performed in 35 of the 161 patients. The diameters and areas of the aortic annulus were evaluated by these three methods and compared. To evaluate the shape of the aortic annuli, eccentricity index (EI) (1 - minimum diameter/long-axis diameter) were calculated. RESULTS: Maximum dimensions of the aortic annulus measured by MDCT were significantly larger than those by 3DTTE and 2DTTE. The aortic annular areas measured by MDCT and 3DTTE were significantly larger than areas by 2DTTE. A good correlation (r = 0.85) was observed between the areas obtained by 3DTTE and MDCT; however, the correlation between the values by 2DTTE and MDCT was rough (r = 0.44). EI values in 46 % of the patients were greater than 0.1, i.e., the aortic annulus was elliptical. CONCLUSION: The images obtained by 3DTTE provided accurate values of the aortic annular area, which were equal to the values measured by MDCT. 3DTTE is a useful method to evaluate the aortic annular geometry. PMID- 27278914 TI - Echocardiography in the diagnosis of apical non-compaction associated with congenital heart diseases. AB - BACKGROUND: Isolated left ventricular non-compaction has been reported extensively. However, apical non-compaction of both ventricles and the interventricular septum (IVS) is not often reported in the literature. The objective of our study is to evolve the echocardiographic diagnostic criteria and to assess the types and impact of the associated lesions in "apical non compaction". METHODS AND RESULTS: Seventy consecutive cases that fulfilled standard echocardiographic criteria for non-compaction of the left ventricle and, in addition, N/C ratio of >3 for the right ventricle and apical IVS formed the material. The age of patients ranged from 3 days to 35 years, with 37 males and 33 females. The associated lesions were present in all 70 cases: 62 had acyanotic (88.6 %) and 8 had cyanotic congenital heart diseases (11.4 %). Of the 70 cases, 18 had pump failure (25.7 %): 8 cases had left ventricular dysfunction, 7 had right ventricular dysfunction, and 3 had biventricular dysfunction; 33 (47.1 %) had pulmonary hypertension, 2 (2.9 %) had thrombus, and 1 (1.4 %) had tachyarrhythmia. Pump failure was worsened by volume overload in 33.9 % and by pressure overload in 8.1 % of cases. Some very rare lesions were detected. All 70 cases had Swiss cheese appearance of the apical half of the IVS, looking like the delta of a river. CONCLUSION: All of the apical non-compaction syndrome cases had associated lesions, mostly acyanotic congenital heart disease with volume overload, rather than obstructive lesions. Transthoracic echocardiography plays an important role in the diagnosis of apical non-compaction syndrome and associated lesions that worsen the pump failure. PMID- 27278915 TI - Double-orifice mitral valve. AB - We report the case of a rare congenital anomaly, a double-orifice mitral valve, in a 21-year-old woman who was asymptomatic and had no history of heart disease. Transthoracic echocardiography revealed two functionally normal orifices mitral valve of equal size. As the presentation in adulthood is rare, echocardiographers should be trained to make the appropriate diagnosis. PMID- 27278916 TI - Hemodynamic influence of triphasic mitral inflow velocity: a case report. PMID- 27278917 TI - Loeffler endocarditis and restrictive cardiomyopathy with biventricular apical thrombi. PMID- 27278918 TI - A case of biventricular involvement of Takotsubo cardiomyopathy: 3D echocardiographic imaging. PMID- 27278919 TI - Erratum to: Low-flow aortic stenosis and preserved left ventricular ejection fraction. PMID- 27278920 TI - TV comedian writes off $15m in US medical debt. PMID- 27278921 TI - Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER ASAP). AB - OBJECTIVE: To compare the efficacy and safety of intravenous ferric carboxymaltose (FCM) with first-line oral ferrous sulfate (FS) in pregnant women with iron deficiency anemia (IDA). MATERIALS AND METHODS: Pregnant women (n=252; gestational weeks 16-33) with IDA were randomized 1:1 to FCM (1000-1500 mg iron) or FS (200 mg iron/day) for 12 weeks. The primary objective was to compare efficacy; secondary objectives included safety and quality of life. RESULTS: Hemoglobin (Hb) levels improved at comparable rates across both treatments; however, significantly more women achieved anemia correction with FCM vs. FS [Hb >=11.0 g/dL; 84% vs. 70%; odds ratio (OR): 2.06, 95% confidence interval (CI): 1.07, 3.97; P=0.031] and within a shorter time frame (median 3.4 vs. 4.3 weeks). FCM treatment significantly improved vitality (P=0.025) and social functioning (P=0.049) prior to delivery. Treatment-related adverse events were experienced by 14 (FCM; 11%) and 19 (FS; 15%) women, with markedly higher rates of gastrointestinal disorders reported with FS (16 women) than with FCM (3 women). Newborn characteristics were similar across treatments. CONCLUSIONS: During late stage pregnancy, FCM may be a more appropriate option than first-line oral iron for rapid and effective anemia correction, with additional benefits for vitality and social functioning. PMID- 27278922 TI - Biphasic insulin Aspart 30 vs. NPH plus regular human insulin in type 2 diabetes patients; a cost-effectiveness study. AB - BACKGROUND: The aim of this study was to compare the efficacy, safety, costs, and cost-effectiveness of biphasic insulin aspart 30 (BIAsp 30) with NPH plus regular human insulin (NPH/Reg) in patients with type 2 diabetes mellitus (T2DM). METHODS: It was a Single-center, parallel-group, randomized, clinical trial (Trial Registration: NCT01889095). One hundred and seventy four T2DM patients with poorly controlled diabetes (HbA1c >= 8 % (63.9 mmol/mol)) were randomly assigned to trial arms (BIAsp 30 and NPH/Reg) and were followed up for 48 weeks. BIAsp 30 was started at an initial dose of 0.2-0.6 IU/Kg in two divided doses and was titrated according to the glycemic status of the patient. Similarly, NPH/Reg insulin was initiated at a dose of 0.2-0.6 IU/Kg with a 2:1 ratio and was subsequently titrated. Level of glycemic control, hypoglycemic events, direct and indirect costs, quality adjusted life year (QALY) and incremental cost effectiveness ratio have been assessed. RESULTS: HbA1c, Fasting plasma glucose (FPG), and two-hour post-prandial glucose (PPG) were improved in both groups during the study (P < 0.05 for all analyses). Lower frequencies of minor, major, and nocturnal hypoglycemic episodes were observed with BIAsp 30 (P < 0.05). Additionally, BIAsp 30 was associated with less weight gain and also higher QALYs (P < 0.05). Total medical and non-medical costs were significantly lower with BIAsp 30 as compared with NPH/Reg (930.55 +/- 81.43 USD vs. 1101.24 +/- 165.49 USD, P = 0.004). Moreover, BIAsp 30 showed lower ICER as a dominant alternative. CONCLUSIONS: Despite being more expensive, BIAsp 30 offers the same glycemic control as to NPH/Reg dose-dependently and also appears to cause fewer hypoglycemic events and to be more cost-effective in Iranian patients with type 2 diabetes. PMID- 27278923 TI - Development of the Japanese version of the Pediatric Quality of Life InventoryTM Transplant Module. AB - BACKGROUND: Health-related quality of life (HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life InventoryTM (PedsQL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity. METHODS: Based on the PedsQL linguistic validation process, the Japanese version of the PedsQL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population. RESULTS: Eighty seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3 7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test-retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed. CONCLUSIONS: Excellent feasibility, reliability, and validity of this Japanese self-report version of the PedsQL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the PedsQL Transplant Module is appropriate for use in clinical and research settings. PMID- 27278924 TI - A pH-dependent charge reversal peptide for cancer targeting. AB - Naturally occurring cationic antimicrobial peptides exhibit not only antimicrobial activity, but also anticancer activity and are expected to be new weapons in cancer treatment. The selectivity for cancer cells over normal cells is at least partly due to the more negative surface of cancer cells. A lower pH in tumor tissue (pH 6.2-6.9) than that in normal tissues (pH 7.3-7.4) has also been utilized to develop anticancer agents. However, cytotoxicity against normal cells at physiological pH is often an issue. Furthermore, acidic regions can be found in some normal tissues such as the kidneys. Therefore, existing approaches to cancer targeting are not fully satisfactory. In this study, we designed a peptide, HE (GIHHWLHSAHEFGEHFVHHIMNS-amide), with a charge that reverses from 1.5 at pH 7.4 to +6 at pH 5.5 for cancer targeting at low pH based on the antimicrobial peptide magainin 2 by introducing 6 His, an additional Glu, and an amidated terminal. HE interacted with cancer-mimicking negatively charged liposomes in a pH-dependent fashion with a midpoint with a pH of 6.5 just above the membrane surface. The peptide killed human renal adenocarcinoma ACHN cells at pH 6.0, but not at pH 7.4, and was nontoxic against human normal glomerular mesangial cells even at this low pH. Thus, the novel peptide may be a promising lead peptide for cancer therapy, although this derivatization resulted in weakened cytotoxicity. PMID- 27278925 TI - 1-Phenyl-3-(2-thiazolyl)-2-thiourea inhibits melanogenesis via a dual-action mechanism. AB - 1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) is a well-characterized dopamine beta hydroxylase inhibitor that prevents 6-hydroxydopamine-induced degenerative neuronal disease. However, the effect of PTTU on melanogenesis has not been reported. In this study, we examined the effect of PTTU on melanogenesis and studied its mechanism of action. We found that PTTU decreased melanin biosynthesis in a dose-dependent manner in normal human epidermal melanocytes (NHEMs). PTTU also inhibited tyrosinase catalytic activity in NHEMs. Moreover, PTTU treatment led to reduced protein levels of tyrosinase in NHEMs, while the protein levels of tyrosinase-related protein-1, tyrosinase-related protein-2, and microphthalmia-associated transcription factor were not affected. However, PTTU treatment did not affect the mRNA expression of tyrosinase. We found that PTTU accelerated tyrosinase degradation via the ubiquitin-dependent proteasome pathway. In summary, we found that PTTU decreased melanin biosynthesis by decreasing the enzymatic activity and stability of tyrosinase. Our results indicate that PTTU could be used as a depigmentation agent for hyperpigmentation disorder. PMID- 27278926 TI - Improvement of hypertension, endothelial function and systemic inflammation following short-term supplementation with red beet (Beta vulgaris L.) juice: a randomized crossover pilot study. AB - Hypertension is a major risk factor for cardiovascular disease and has a prevalence of about one billion people worldwide. It has been shown that adherence to a diet rich in fruits and vegetables helps in decreasing blood pressure (BP). This study aimed to investigate the effect of raw beet juice (RBJ) and cooked beet (CB) on BP of hypertensive subjects. In this randomized crossover study, 24 hypertensive subjects aged 25-68 years old were divided into two groups. One group took RBJ for 2 weeks and the other group took CB. After 2 weeks of treatment, both groups had a washout for 2 weeks then switched to the alternate treatment. Each participant consumed 250 ml day(-1) of RBJ or 250 g day(-1) of CB each for a period of 2 weeks. Body weight, BP, flow-mediated dilation (FMD), lipid profile and inflammatory parameters were measured at baseline and after each period. According to the results, high-sensitivity C reactive protein (hs-CRP) and tumour necrosis factor alpha (TNF-alpha) were significantly lower and FMD was significantly higher after treatment with RBJ compared with CB (P<0.05). FMD was significantly (P<0.05) increased, but systolic and diastolic BP, intracellular adhesion molecule-1 (ICAM-1), vascular endothelial adhesion molecule-1 (VCAM-1), hs-CRP, interleukin-6, E-selectin and TNF-alpha were significantly (P<0.05) decreased with RBJ or CB. Total antioxidant capacity was increased and non-high-density lipoprotein (HDL), low-density lipoprotein (LDL) and total cholesterol (TC) were decreased with RBJ but not with CB. Although both forms of beetroot were effective in improving BP, endothelial function and systemic inflammation, the raw beetroot juice had greater antihypertensive effects. Also more improvement was observed in endothelial function and systemic inflammation with RBJ compared with CB. PMID- 27278928 TI - [Not Available]. PMID- 27278927 TI - Usefulness of the renal resistive index to predict an increase in urinary albumin excretion in patients with essential hypertension. AB - Microalbuminuria is a risk factor for cardiovascular events and death in hypertensive patients. Patients who are expected to increase albuminuria need strict blood pressure control. In the present study, we assessed the association between the renal resistive index (RI) and future increases in albuminuria in patients with essential hypertension. Sixty-six patients with essential hypertension were included in the study. Univariate and multivariate logistic regression analyses were used to identify the factors, including renal RI, that were significant independent determinants of increased in urinary albumin excretion (UAE), defined as an increase of >50% in the urinary albumin-to creatinine ratio over 2 years. Receiver operator characteristics curve analysis was used to select the optimal cut-off point that predicted an increase in UAE. RI was the only significant variable that predicted the increase in UAE, with the optimal cut-off value of renal RI that predicted this increase being 0.71 (sensitivity 52.4% and specificity 84.4%). Renal RI is associated with the future increase in albuminuria in patients with essential hypertension. PMID- 27278930 TI - Cnidoscolus mosaic leaf deformation virus: a novel begomovirus infecting euphorbiaceous plants in Brazil. AB - Begomoviruses have been detected infecting the weed Cnidoscolus urens (family Euphorbiaceae) since 2004, but the viral species to which these viruses belonged was not known. Here, we report for the first time the complete genome sequence of a bipartite begomovirus obtained from C. urens collected in the state of Alagoas, Brazil. This isolate met the criteria to be classified as a member of a new begomovirus species, and the tentative name cnidoscolus mosaic leaf deformation virus (CnMLDV) is proposed. Pairwise sequence comparisons and phylogenetic analysis showed that the DNA-A genomic component of CnMLDV is most closely related to that of passionfruit severe leaf distortion virus, with 86.3 % nucleotide sequence identity. PMID- 27278929 TI - Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening. AB - Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5 dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5 dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5 dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID- 27278931 TI - Structure and function of chicken interleukin-1 beta mutants: uncoupling of receptor binding and in vivo biological activity. AB - Receptor-binding and subsequent signal-activation of interleukin-1 beta (IL 1beta) are essential to immune and proinflammatory responses. We mutated 12 residues to identify sites important for biological activity and/or receptor binding. Four of these mutants with mutations in loop 9 (T117A, E118K, E118A, E118R) displayed significantly reduced biological activity. Neither T117A nor E118K mutants substantially affected receptor binding, whereas both mutants lack the IL-1beta signaling in vitro but can antagonize wild-type (WT) IL-1beta. Crystal structures of T117A, E118A, and E118K revealed that the secondary structure or surface charge of loop 9 is dramatically altered compared with that of wild-type chicken IL-1beta. Molecular dynamics simulations of IL-1beta bound to its receptor (IL-1RI) and receptor accessory protein (IL-1RAcP) revealed that loop 9 lies in a pocket that is formed at the IL-1RI/IL-1RAcP interface. This pocket is also observed in the human ternary structure. The conformations of above mutants in loop 9 may disrupt structural packing and therefore the stability in a chicken IL-1beta/IL-1RI/IL-1RAcP signaling complex. We identify the hot spots in IL-1beta that are essential to immune responses and elucidate a mechanism by which IL-1beta activity can be inhibited. These findings should aid in the development of new therapeutics that neutralize IL-1 activity. PMID- 27278932 TI - Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells. AB - BACKGROUND: ADPKD is a renal pathology caused by mutations of PKD1 and PKD2 genes, which encode for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 plays an important role regulating several signal transducers, including cAMP and mTOR, which are involved in abnormal cell proliferation of ADPKD cells leading to the development and expansion of kidney cysts that are a typical hallmark of this disease. Therefore, the inhibition of both pathways could potentiate the reduction of cell proliferation enhancing benefits for ADPKD patients. METHODS: The inhibition of cAMP- and mTOR-related signalling was performed by Cl-IB-MECA, an agonist of A3 receptors, and rapamycin, respectively. Protein kinase activity was evaluated by immunoblot and cell growth was analyzed by direct cell counting. RESULTS: The activation of A3AR by the specific agonist Cl-IB-MECA causes a marked reduction of CREB, mTOR, and ERK phosphorylation in kidney tissues of Pkd1 flox/-: Ksp-Cre polycystic mice and reduces cell growth in ADPKD cell lines, but not affects the kidney weight. The combined sequential treatment with rapamycin and Cl-IB-MECA in ADPKD cells potentiates the reduction of cell proliferation compared with the individual compound by the inhibition of CREB, mTOR, and ERK kinase activity. Conversely, the simultaneous application of these drugs counteracts their effect on cell growth, because the inhibition of ERK kinase activity is lost. CONCLUSION: The double treatment with rapamycin and Cl-IB-MECA may have synergistic effects on the inhibition of cell proliferation in ADPKD cells suggesting that combined therapies could improve renal function in ADPKD patients. PMID- 27278934 TI - Mortality and illicit drug dependence among hemodialysis patients in the United States: a retrospective cohort analysis. AB - BACKGROUND: Illicit drug use is common and known to cause and exacerbate a wide spectrum of kidney disease, often leading to end-stage renal disease (ESRD), but little is known about its prevalence or associated mortality among incident hemodialysis patients. METHODS: This study is a retrospective cohort analysis using data obtained from the United States Renal Data System. We assembled a cohort of 511,821 incident hemodialysis patients age 20 years and older who initiated hemodialysis between January 1, 2006 and December 31, 2010. Illicit drug dependence was defined by comorbidity on the ESRD Medical Evidence Report (Form CMS-2728). We performed survival analysis to examine the association of drug dependence with overall mortality and mortality due to diagnoses that can be associated with intravenous drug use (drug-sensitive diagnoses) in the first year after initiating hemodialysis. RESULTS: Drug dependence was recorded for 1.5 % (n = 7,461). Drug dependence was independently associated with a 1.3-fold and 2.5 fold higher hazard of overall mortality and mortality due to a potentially drug sensitive diagnosis [adjusted hazard ratio (AHR) 1.34 (1.27-1.41) and 2.54 (2.05 3.14), p < 0.001, respectively]. This association varied significantly by age (pinteraction < 0.001), with a 9-fold higher hazard of mortality due to a potentially drug-sensitive diagnosis among the youngest patients with drug dependence [AHR 9.21 (5.15-16.44), p < 0.001]. CONCLUSION: Illicit drug dependence is a burden within the ESRD program and is strongly associated with premature mortality, particularly among younger patients. Targeted intervention is needed to help reduce this burden. PMID- 27278933 TI - A multicentre demonstration project to evaluate the effectiveness and acceptability of the web-based Joint Asia Diabetes Evaluation (JADE) programme with or without nurse support in Chinese patients with Type 2 diabetes. AB - AIMS: To test the hypothesis that delivery of integrated care augmented by a web based disease management programme and nurse coordinator would improve treatment target attainment and health-related behaviour. METHODS: The web-based Joint Asia Diabetes Evaluation (JADE) and Diabetes Monitoring Database (DIAMOND) portals contain identical built-in protocols to integrate structured assessment, risk stratification, personalized reporting and decision support. The JADE portal contains an additional module to facilitate structured follow-up visits. Between January 2009 and September 2010, 3586 Chinese patients with Type 2 diabetes from six sites in China were randomized to DIAMOND (n = 1728) or JADE, plus nurse coordinated follow-up visits (n = 1858) with comprehensive assessments at baseline and 12 months. The primary outcome was proportion of patients achieving >= 2 treatment targets (HbA1c < 53 mmol/mol (7%), blood pressure < 130/80 mmHg and LDL cholesterol < 2.6 mmol/l). RESULTS: Of 3586 participants enrolled (mean age 57 years, 54% men, median disease duration 5 years), 2559 returned for repeat assessment after a median (interquartile range) follow-up of 12.5 (4.6) months. The proportion of participants attaining >= 2 treatment targets increased in both groups (JADE 40.6 to 50.0%; DIAMOND 38.2 to 50.8%) and there were similar absolute reductions in HbA1c [DIAMOND -8 mmol/mol vs JADE -7 mmol/mol (-0.69 vs 0.62%)] and LDL cholesterol (DIAMOND -0.32 mmol/l vs JADE -0.28 mmol/l), with no between-group difference. The JADE group was more likely to self-monitor blood glucose (50.5 vs 44.2%; P = 0.005) and had fewer defaulters (25.6 vs 32.0%; P < 0.001). CONCLUSIONS: Integrated care augmented by information technology improved cardiometabolic control, with additional nurse contacts reducing the default rate and enhancing self-care. (Clinical trials registry no.: NCT01274364). PMID- 27278935 TI - The way to a man's heart is through his stomach?: a mixed methods study on causal mechanisms through which cash and in-kind food transfers decreased intimate partner violence. AB - BACKGROUND: Intimate partner violence (IPV) is highly prevalent and has detrimental effects on the physical and mental health of women across the world. Despite emerging evidence on the impacts of cash transfers on intimate partner violence, the pathways through which reductions in violence occur remain under explored. A randomised controlled trial of a cash and in-kind food transfer programme on the northern border of Ecuador showed that transfers reduced physical or sexual violence by 30 %. This mixed methods study aimed to understand the pathways that led to this reduction. METHODS: We conducted a mixed methods study that combined secondary analysis from a randomised controlled trial relating to the impact of a transfer programme on IPV with in-depth interviews and focus group discussions with male and female beneficiaries. A sequential analysis strategy was followed, whereby qualitative results guided the choice of variables for the quantitative analysis and qualitative insights were used to help interpret the quantitative findings. RESULTS: We found qualitative and quantitative evidence that the intervention led to reductions in IPV through three pathways operating at the couple, household and individual level: i) reduced day-to-day conflict and stress in the couple; ii) improved household well being and happiness; and iii) increased women's decision making, self-confidence and freedom of movement. We found little evidence that any type of IPV increased as a result of the transfers. DISCUSSION: While cash and in-kind transfers can be important programmatic tools for decreasing IPV, the positive effects observed in this study seem to depend on circumstances that may not exist in all settings or programmes, such as the inclusion of a training component. Moreover, the programme built upon rather than challenged traditional gender roles by targeting women as transfer beneficiaries and framing the intervention under the umbrella of food security and nutrition - domains traditionally ascribed to women. CONCLUSIONS: Transfers destined for food consumption combined with nutrition training reduced IPV among marginalised households in northern Ecuador. Evidence suggests that these reductions were realised by decreasing stress and conflict, improving household well-being, and enhancing women's decision making, self confidence and freedom of movement. TRIAL REGISTRATION: ClinicalTrials.gov NCT02526147 . Registered 24 August 2015. PMID- 27278936 TI - No filters, no fridges: a method for preservation of water samples for eDNA analysis. AB - BACKGROUND: Advancements in the detection of environmental DNA (eDNA) for detecting species of interest will likely allow for expanded use of these techniques in the field. One obstacle that continues to hinder applications in the field is the requirement of a cold chain of storage for water samples containing eDNA. While eDNA has been successfully preserved using Longmire's lysis buffer applied to filters, it has yet to be tried with freshwater samples collected for eDNA detection of an invasive species. We tested the utility of Longmire's solution (100 mM Tris, 100 mM EDTA, 10 mM NaCl, 0.5 % SDS, 0.2 % sodium azide) as an additive to freshwater samples for preservation of eDNA. RESULTS: Environmental DNA was effectively preserved in 15 mL water samples with Longmire's solution added; eDNA positive detection was comparable to freezing the samples at -80 degrees C and occurred out to 56 days at the highest concentration (5 mL Longmire's solution: 15 mL sample water). Medium and low concentrations of Longmire's solution added to 15 mL of sample water generally preserved eDNA out to 56 days but not as well as did freezing or application of the highest concentration of Longmire's lysis buffer. Treatment and degradation time had a significant effect on average DNA concentration of samples, although not the interaction of treatment and time. Perfect detection occurred out to 56 days with the high Longmire's treatment group but DNA concentration was significantly lower at this time point compared to 28 days. CONCLUSION: We conclude that Longmire's lysis buffer is a viable alternative to cold chain storage that can simplify the collection of eDNA by eliminating the need for filtering and allow more time for sample collection when added at our highest concentration (1 part Longmire's:3 parts water sample), which could translate to an increase in the chances of detecting a rare or elusive species. PMID- 27278937 TI - Postmenopausal hyperandrogenism: the under-recognized value of inhibins. AB - We report a 70-year-old female presenting with increased libido and mild but rapid onset virilism. Investigations showed markedly elevated androstenedione and 17 hydroxyprogesterone misdirecting to possible late-onset congenital adrenal hyperplasia. High serum testosterone and oestrogens with suppressed gonadotrophins, however, indicated an androgen-secreting tumour. A normal dehydroepiandrosterone sulphate and elevated inhibins A and B indicated the tumour was ovarian in origin, which was confirmed on pelvic examination and imaging. At laparotomy, a right ovarian sertoliform endometrioid carcinoma was removed, following which the patient developed menopausal vasomotor symptoms and improvement of her virilism. Serum testosterone, oestradiol, inhibins A and B became undetectable, gonadotrophins appropriately increased and 17 hydroxyprogesterone and androstenedione normalized. We propose that inhibins may be of diagnostic value and should be included in investigative algorithms of females with virilization and hyperandrogenaemia, especially if postmenopausal. Androgen-secreting tumours must be excluded before raised 17 hydroxyprogesterone concentrations are used to diagnose late-onset congenital adrenal hyperplasia in females with new-onset virilization. PMID- 27278938 TI - Ultrasound inflammation imaging in rats with myocardial ischemia-reperfusion: evaluation by non-specific targeted contrast microbubbles. AB - BACKGROUND: Reports on ultrasound inflammation imaging with non-specific targeted microbubbles in the heart have been scarce. We investigated whether inflammation induced by myocardial ischemia-reperfusion in rats could be evaluated by ultrasound inflammation imaging with non-specific targeted microbubbles. METHODS: Six rats subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by 4 h of reperfusion (ischemia group) and 4 rats subjected to the sham operation (sham group) were used. Ultrasound inflammation imaging was performed 4 h after reperfusion, and non-circulating signal intensity (SI), which reflects the signal derived from microbubbles phagocytosed by neutrophils in inflamed tissue, was calculated by the SI difference between the initial and subsequent imaging both in the LAD and non-LAD areas. The accumulation of neutrophils was confirmed by myeloperoxidase (MPO) staining. RESULTS: Non circulating SI in the LAD area was significantly greater for the ischemia group than the sham group [5.19 +/- 2.19 (ischemia) vs. 0.31 +/- 0.13 (sham) dB, p < 0.01]. Non-circulating SI in the LAD area was significantly higher than that in the non-LAD area when compared in the same rat of the ischemia group [5.19 +/- 2.19 (LAD) vs. 0.18 +/- 0.64 (non-LAD) dB, p < 0.01]. MPO-positive cells were confirmed in the LAD area of the ischemia group. CONCLUSION: Inflammation induced by myocardial ischemia-reperfusion in rats could be quantitatively assessed by ultrasound inflammation imaging with non-specific targeted microbubbles. PMID- 27278939 TI - Reconsiderations of mitral stenosis: rheumatic mitral valve repair and the Wilkins score. AB - BACKGROUND: Mitral valve repair is a feasible treatment option in patients with rheumatic mitral valve disease, but it is not always successful. Mitral valve replacement is generally the surgical treatment of choice in such patients. We aimed to examine whether the Wilkins score can predict the feasibility of surgical repair in such patients. METHODS: Mitral valve surgery was performed on 14 patients by the same surgeon (A.A.). Five patients underwent mitral valve repair (group I), and nine patients underwent mitral valve replacement (group II). The Wilkins scores were determined by assessing echocardiography findings. The selection of mitral valve repair or replacement was based on the intraoperative findings and the preferences of the same surgeon (A.A.). In group I, we performed chordal reconstruction, augmentation of the posterior leaflet, resection of chordae, decalcification of the commissure, commissurotomy, slicing of the anterior leaflet, division of the papillary muscle, and ring annuloplasty in various combinations. RESULTS: There were no significant differences between the two groups with regard to any component of the preoperative Wilkins score. There was no significant difference in the pre- and postoperative scores in group I; however, the mitral valve orifice area was significantly improved after the operation (pre- and postoperative mean values: 1.3 +/- 0.3 and 2.0 +/- 0.4, P < 0.05). CONCLUSION: Mitral valve repair is effective in treating rheumatic mitral stenosis. However, the Wilkins score may not be useful in predicting the feasibility of mitral repair. PMID- 27278940 TI - Left ventricular remodeling after myocardial infarction impairs early diastolic, but not systolic, function in the radial direction in the remote normal region. AB - BACKGROUND: It is acknowledged that expansion of the remote normal region of the left ventricle causes remodeling after myocardial infarction (MI). However, the characteristics of that region have not been fully elucidated. METHODS: We studied 13 patients with atypical chest pain (controls) and 15 patients with a prior anterior MI who underwent cardiac catheterization. With Doppler strain imaging, we measured the peak radial myocardial systolic strain and peak radial early diastolic strain rate at the posterior wall of the left ventricle. None of the patients with atypical chest pain exhibited significant stenosis of the three major coronary arteries or left ventricular (LV) wall motion abnormality in cardiac catheterization. The patients with a prior anterior MI had single anterior descending artery disease without wall motion abnormality in the LV inferoposterior wall. LV ejection fraction and the LV relaxation time constant were also measured. RESULTS: The LV ejection fraction was significantly smaller in patients with a prior MI compared to controls. The peak radial systolic strain in the LV posterior wall was not significantly different between the patients with a prior MI and controls (125 +/- 49 vs. 122 +/- 29%). In contrast, the peak radial early diastolic strain rate in the same area was significantly lower in the patients with a prior MI than in controls (-7.4 +/- 2.7 vs. -13.2 +/- 4.0 s( 1), p < 0.001). Peak early diastolic radial strain rate was significantly correlated with the LV relaxation time constant in all patients (r = 0.69, p < 0.001). CONCLUSION: LV remodeling after an MI impairs local early diastolic myocardial function in the remote normal region and it is related to global LV diastolic dysfunction. PMID- 27278941 TI - Two cases of quadricuspid aortic valve. AB - Quadricuspid aortic valve (QAV) is a rare congenital aortic valve anomaly. We present two cases of QAV diagnosed by using echocardiography including transesophageal echocardiography (TEE) and cardiac computed tomography (CT). The first case, QAV with four equal-sized cusps, was identified in a 58-year-old man. The second case, QAV with a small accessory cusp between the right coronary and non-coronary cusp, was identified in a 42-year-old man. TEE and cardiac CT could lead to accurate diagnosis of QAV. QAV in these two patients could be diagnosed before indication for surgery but it is necessary to continue careful follow-up. PMID- 27278942 TI - Asymptomatic fistula from a giant aneurysmatic left anterior descending artery to the right ventricular outflow tract. AB - Coronary artery fistulas are unusual congenital or acquired coronary artery abnormalities in which blood is shunted into a cardiac chamber, great vessel or other structure, bypassing the myocardial capillary network (Jung et al. in Cardiovasc Ultrasound 5:10, 2007). We present a young adult patient with an asymptomatic fistula from a giant aneurysmatic left anterior descending artery to the right ventricular outflow tract, first diagnosed by echocardiography examination and further confirmed by 128-slice computed tomography coronary angiography. PMID- 27278943 TI - Infective endocarditis mimicking left atrial myxoma. AB - Infective endocarditis (IE) is an inflammatory disease of the endocardium and can be seen with various clinical presentations such as large intracardiac vegetations. The differential diagnosis of intracardiac mass is important to guide the management. Echocardiography is of critical use in the diagnosis of intracardiac mass. Herein we present a rare case with left atrial IE and a giant vegetation mimicking left atrial myxoma. PMID- 27278944 TI - Acute myocardial infarction in a young adult patient with simultaneous total occlusion of double coronary arteries. AB - We report an otherwise healthy 16-year-old male patient with simultaneous double vessel acute myocardial infarction. Coronary angiography (CAG) showed simultaneous total occlusion of the left anterior descending artery (LAD) and the left circumflex artery (LCX). Emergent percutaneous coronary intervention (PCI) was performed on the diseased lesions. After PCI, coronary artery aneurysms were found in both the LAD and LCX. The patient was discharged after a 56-day hospitalization. The New York Heart Association (NYHA) Functional Classification at discharge was II. Medical therapy became ineffective over time because of exacerbated ischemic mitral regurgitation; successful mitral annuloplasty was performed. The post-operative course was uneventful. PMID- 27278945 TI - Left ventricular apical aneurysm due to unrecognized sarcoidosis. AB - A 47-year-old woman was hospitalized for syncope. An electrocardiogram showed complete right bundle branch block and T-wave inversion in leads III, aVF, and V2 4. Cardiac catheterization was performed since the echocardiogram demonstrated the existence of a left ventricular apical aneurysm and apical thrombus. Coronary angiography revealed normal coronary arteries. An endomyocardial biopsied specimen from the right ventricular apical wall demonstrated typical noncaseating granulomas with giant cells. There was no evidence suggesting the involvement of other systemic organs. The patient was diagnosed as having cardiac sarcoidosis. Cardiac sarcoidosis should be considered within a spectrum of diseases that cause left ventricular apical aneurysm. PMID- 27278946 TI - Isolated true parachute mitral valve in an asymptomatic elderly patient. AB - We report the extremely rare case of a 73-year-old asymptomatic patient who has an isolated true parachute mitral valve (PMV). In the echocardiographic examination, the parasternal long-axis view showed a single papillary muscle. The short-axis view revealed the presence of a symmetric mitral valve orifice with all chordae attaching to a large anterolateral papillary muscle. Because detailed examination did not reveal the presence of other complications, this patient was diagnosed as an isolated true PMV. PMID- 27278947 TI - Giant coronary sinus and a review of the literature. AB - We report a case of persistent left superior caval vein whom presented with angina pectoris and exertional dyspnea. Echocardiography showed wall motion disturbances with an ejection fraction of 40% and a very large coronary sinus. Our case is a very rare case with a very large coronary sinus presented with angina pectoris. PMID- 27278948 TI - Unusual biatrial thrombus in mitral stenosis. PMID- 27278949 TI - Tricuspid valvular dysplasia and its differentiation from Ebstein's anomaly. PMID- 27278950 TI - After-the-fact recognition of myocardial ischemic insult: significance of post systolic thickening evaluated by speckle tracking echocardiography. PMID- 27278951 TI - A "ping-pong ball" in the left ventricle. PMID- 27278952 TI - Mechanism of tricuspid regurgitation in corrected transposition of great arteries. PMID- 27278953 TI - Floating and entangled long right atrial thrombus mimicking myxoma. PMID- 27278954 TI - A 78-year-old case of Bland-White-Garland syndrome with conservative therapy. PMID- 27278955 TI - Simultaneous examination of the aorta in echocardiography of patients with coronary artery disease. PMID- 27278956 TI - Colorectal Cancer in Young African Americans: Is It Time to Revisit Guidelines and Prevention? AB - BACKGROUND & AIMS: Previous studies have suggested an increase in the incidence of colorectal cancer (CRC) in young adults (younger than 50 years). Among older people, African Americans have disproportionally higher CRC incidence and mortality. We assessed whether this CRC disparity also applies to CRC diagnosed among young people. METHODS: Using the Surveillance, Epidemiology, and End Results cancer registries, a population-based cancer registry covering 25.6 % of the United States' African American population, we identified patients diagnosed with CRC between the years of 2000-2012. The age-adjusted rates for non-Hispanic whites (NHW), African Americans, and Asian-Pacific Islanders (API) were calculated for the age categories 20-24, 25-29, 30-34, 35-39, and 40-44. RESULTS: CRC age-adjusted incidence is increasing among all three racial groups and was higher for African Americans compared to NHW and API across all years 2000-2012 (P < 0.001). Stage IV CRC was higher in African Americans compared with NHW, while there was higher stage III CRC in API compared with NHWs. CONCLUSION: CRC incidence is increasing among the young in all racial groups under study. This increase in frequency of CRC is true among young African American adults who display highly advanced tumors in comparison with other races. While the present attention to screening seems to have decreased CRC prevalence in individuals older than 50, special attention needs to be addressed to young African American adults as well, to counter the observed trend, as they have the highest incidence of CRC among young population groups by race/ethnicity. PMID- 27278958 TI - The phenomenon of drop in output at larger field sizes for telecobalt units. AB - It is known that the output factors (OPFs) for external-beam radiotherapy units increase with field size due to increased scattered radiation from the collimator system. Saturation in the OPF value is generally reported beyond approximately 30 * 30 cm(2). For the first time, to the best of our knowledge, we report on a drop in OPF values, although marginal, measured for a telecobalt machine beyond the 38 * 38 cm(2) field size. We believe that reporting and explaining the results will lead to a better understanding of the scatter composition of the radiation from telecobalt machines. This also has the potential to impact the estimation of low dose regions in patients, in addition to being a purely scientific inquiry. We used Monte Carlo (MC) simulations to validate the measured values. The MC data showed that the decrease in OPF was due to decreased scatter from the machine head. PMID- 27278957 TI - A Comparative Study of Treatment-Emergent Adverse Events Following Use of Common Bowel Preparations Among a Colonoscopy Screening Population: Results from a Post Marketing Observational Study. AB - BACKGROUND: Colonoscopy may be one of the most frequent elective procedures in older adults and is associated with a low occurrence of complications. However, reduction of risks attributable to the bowel preparation may be achieved with the use of effective and safer products. AIM: The aim of this study was to examine the incidence of treatment-emergent adverse events (TEAEs) associated with SUPREP((r)) [oral sulfate solution (OSS)] and other common prescription bowel preparations (non-OSS). METHODS: This real-world, observational study used de identified health insurance claims and laboratory results to identify TEAEs in the 3 months following screening colonoscopy in adults with a prescription for a bowel preparation in the prior 60 days. The unadjusted and adjusted (controlling for patient risk factors) cumulative incidences of TEAEs were estimated using Kaplan-Meier and Poisson regression, respectively. RESULTS: Among patients >=45 years, the overall cumulative incidence was significantly lower (p < 0.001) in the OSS cohort than in the non-OSS cohort (unadjusted: 2.31 vs. 2.89 %; adjusted: 1.61 vs. 1.95 %), with significantly lower acute cardiac conditions (1.56 vs. 1.90 %; p < 0.001), renal failure/other serious renal diseases (OSS: 0.21 %, non OSS: 0.32 %; p < 0.001), and serum electrolyte abnormalities (OSS: 0.39 %, non OSS: 0.49 %; p = 0.017). There were no significant differences between cohorts in death, seizure disorders, aggravation of gout, and ischemic colitis. Results were similar in the adjusted cumulative incidences. CONCLUSIONS: In actual use, the overall cumulative incidence of TEAEs was significantly lower in the OSS cohort, demonstrating that OSS is as safe as, or possibly safer than, non-OSS prescription bowel preparations. PMID- 27278959 TI - Curcumin inhibits aerobic glycolysis in hepatic stellate cells associated with activation of adenosine monophosphate-activated protein kinase. AB - Activation of hepatic stellate cells (HSCs) is characterized by expression of extracellular matrix and loss of adipogenic phenotype during liver fibrogenesis. Emerging evidence suggests that HSCs adopt aerobic glycolysis during activation. The present work aimed at investigating whether the anti-fibrogenic effects of curcumin was associated with interfering with glycolysis in HSCs. Primary rat HSCs were cultured in vitro. We demonstrated that inhibition of glycolysis by 2 deoxyglucose or galloflavin reduced the expression of alpha-smooth muscle actin (alpha-SMA) and alpha1(I)procollagen at both mRNA and protein levels, and increased the intracellular lipid contents and upregulated the gene and protein expression of adipogenic transcription factors C/EBPalpha and PPAR-gamma in HSCs. Curcumin at 20 MUM produced similar effects. Moreover, curcumin decreased the expression of hexokinase (HK), phosphofructokinase-2 (PFK2), and glucose transporter 4 (glut4), three key glycolytic parameters, at both mRNA and protein levels. Curcumin also reduced lactate production concentration-dependently in HSCs. Furthermore, curcumin increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), but AMPK inhibitor BML-275 significantly abolished the curcumin downregulation of HK, PFK2, and glut4. In addition, curcumin inhibition of alpha-SMA and alpha1(I)procollagen was rescued by BML-275, and curcumin upregulation of C/EBPalpha and PPAR-gamma was abrogated by BML-275. These results collectively indicated that curcumin inhibited glycolysis in an AMPK activation-dependent manner in HSCs. We revealed a novel mechanism for curcumin suppression of HSC activation implicated in antifibrotic therapy. (c) 2016 IUBMB Life, 68(7):589-596, 2016. PMID- 27278960 TI - A Nomogram to predict parotid gland overdose in head and neck IMRT. AB - PURPOSES: To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). MATERIAL AND METHODS: Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. RESULTS: Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. CONCLUSION: Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning. PMID- 27278961 TI - Biotransformation and Rearrangement of Laromustine. AB - This review highlights the recent research into the biotransformations and rearrangement of the sulfonylhydrazine-alkylating agent laromustine. Incubation of [(14)C]laromustine with rat, dog, monkey, and human liver microsomes produced eight radioactive components (C-1 to C-8). There was little difference in the metabolite profile among the species examined, partly because NADPH was not required for the formation of most components, which instead involved decomposition and/or hydrolysis. The exception was C-7, a hydroxylated metabolite, largely formed by CYP2B6 and CYP3A4/5. Liquid chromatography multistage mass spectrometry (LC-MS(n)) studies determined that collision-induced dissociation, and not biotransformation or enzyme catalysis, produced the unique mass spectral rearrangement. Accurate mass measurements performed with a Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) significantly aided determination of the elemental compositions of the fragments and in the case of laromustine revealed the possibility of rearrangement. Further, collision induced dissociation produced the loss of nitrogen (N2) and methylsulfonyl and methyl isocyanate moieties. The rearrangement, metabolite/decomposition products, and conjugation reactions were analyzed utilizing hydrogen-deuterium exchange, exact mass, (13)C-labeled laromustine, nuclear magnetic resonance spectroscopy (NMR), and LC-MS(n) experiments to assist with the assignments of these fragments and possible mechanistic rearrangement. Such techniques produced valuable insights into these functions: 1) Cytochrome P450 is involved in C-7 formation but plays little or no role in the conversion of [(14)C]laromustine to C-1 through C-6 and C-8; 2) the relative abundance of individual degradation/metabolite products was not species-dependent; and 3) laromustine produces several reactive intermediates that may produce the toxicities seen in the clinical trials. PMID- 27278962 TI - Mercury Human Exposure in Populations Living Around Lake Tana (Ethiopia). AB - A survey carried out in Lake Tana in 2015 found that Hg levels in some fish species exceeded internationally accepted safe levels for fish consumption. The current study assesses human exposure to Hg through fish consumption around the Lake Tana. Of particular interest was that a dietary intake of fishes is currently a health risk for Bihar Dar residents and anglers. Hair samples were collected from three different groups: anglers, college students and teachers, and daily laborers. A questionary includes gender, age, weight, activity. Frequency of fish consumption and origin of the eaten fish were completed by each participant. Mercury concentrations in hair were significantly higher (P value <0.05) for anglers (mean +/- standard deviation 0.120 +/- 0.199 MUg/g) than college students (mean +/- standard deviation 0.018 +/- 0.039 MUg/g) or daily workers (mean +/- standard deviation 16 +/- 9.5 ng/g). Anglers consumed fish more often than daily workers and college group. Moreover, there was also a strong correlation (P value <0.05) between the logarithms of total mercury and age associated with mercury concentration in scalp hair. Mercury concentrations in the hair of men were on average twice the value of the women. Also, users of skin lightening soap on a daily basis had 2.5 times greater mercury in scalp hair than non-users. Despite the different sources of mercury exposure mentioned above, the mercury concentrations of the scalp hair of participants of this study were below levels deemed to pose a threat to health. PMID- 27278963 TI - Mapping Fifteen Trace Elements in Human Seminal Plasma and Sperm DNA. AB - Studies suggest a relationship between semen quality and the concentration of trace elements in serum or seminal plasma. However, trace elements may be linked to DNA and capable of altering the gene expression patterns. Thus, trace element interactions with DNA may contribute to the mechanisms for a trans-generational reproductive effect. We developed an analytical method to determine the amount of trace elements bound to the sperm DNA, and to estimate their affinity for the sperm DNA by the ratio: R = Log [metal concentration in the sperm DNA/metal concentration in seminal plasma]. We then analyzed the concentrations of 15 trace elements (Al, Cd, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Ti, V, Zn, As, Sb, and Se) in the seminal plasma and the sperm DNA in 64 normal and 30 abnormal semen specimens with Inductively Coupled Plasma/Mass Spectrometry (ICP-MS). This study showed all trace elements were detected in the seminal plasma and only metals were detected in the sperm DNA. There was no correlation between the metals' concentrations in the seminal plasma and the sperm DNA. Al had the highest affinity for DNA followed by Pb and Cd. This strong affinity is consistent with the known mutagenic effects of these metals. The lowest affinity was observed for Zn and Ti. We observed a significant increase of Al linked to the sperm DNA of patients with oligozoospermia and teratozoospermia. Al's reproductive toxicity might be due to Al linked to DNA, by altering spermatogenesis and expression patterns of genes involved in the function of reproduction. PMID- 27278964 TI - Correlates of Forced Sex Among Young Men Who Have Sex With Men in Yangon and Monywa, Myanmar. AB - Forced sex at an early age is associated with a variety of negative factors including increased illness, high-risk sexual and substance-use behaviors, and mental and psychological stress. These sequelae may be compounded for men who have sex with men (MSM), especially young MSM and those with feminine gender identity and expression. This survey examined the prevalence and associations of forced sex among young MSM in two cities in Myanmar. In 2013-2014, surveys using respondent-driven sampling collected data on 200 young MSM in Yangon and 200 in Monywa. One quarter of young MSM in Yangon and 21 % in Monywa reported ever experiencing forced sex. In a multivariable model, having problems with family members and having any MSM friends with many partners had higher odds of experiencing forced sex. Having maternal acceptance of same-sex attraction (compared to acceptance by both parents) and becoming aware of their same-sex attraction at or above the age of 16 had lower odds of experiencing forced sex. Focused research is needed to understand the family and other social dynamics affecting vulnerability to forced sex, as well as specific sexual risks associated with forced sex among young MSM, including HIV acquisition and transmission risks. PMID- 27278966 TI - Beyond Heterosexual, Bisexual, and Homosexual: A Diversity in Sexual Identity Expression. PMID- 27278965 TI - Reasons for Non-Disclosure of Sexual Orientation Among Behaviorally Bisexual Men: Non-Disclosure as Stigma Management. AB - Although bisexual men are known to be less likely to disclose their sexual orientation to others than gay men, the reasons why bisexual men choose or feel unable to disclose have received minimal research attention. To examine the reasons behaviorally bisexual men offer for not disclosing to their friends, family, and female partners, in-depth interviews were conducted with an ethnically diverse sample of 203 men who had not disclosed their same-sex behavior to their female sexual partners in New York City. Men were recruited from multiple venues and online sources using a targeted sampling approach. Transcripts were thematically analyzed using Atlas.ti software. Contrary to the theory that non-disclosure is due to uncertainty about one's sexual identity, the reasons offered for non-disclosure revealed that it was largely a method to avoid stigmatizing reactions from others. Men reported a number of specific reasons for non-disclosure, including (1) anticipation of negative emotional reactions; (2) anticipation of negative changes in relationships; (3) belief that others held stigmatizing attitudes toward homosexuality; (4) prior experience with negative reactions to disclosure; (5) wanting to maintain others' perceptions of him; (6) fear that those told would disclose to additional people; and (7) fear of rejection due to culture or religion. These findings provide insights into the reasons why many behaviorally bisexual men choose not to disclose, potential reasons why bisexual and gay men differ in the extent to which they disclose, and potential reasons why some bisexual men report greater emotional distress than gay men. Further, they suggest that greater attention needs to be placed on addressing the stigmatizing contexts that confront bisexual men and providing them with strategies to manage stigma. PMID- 27278967 TI - General practitioners' approach to malingering in basic military training centres. AB - OBJECTIVES: Malingering can be defined as the abuse of the right to benefit from the health services. In this study, the frequency of the malingering cases in Basic Military Training Centres (BMTCs) and the behaviours and the attitudes of the military physicians towards the recruits who are suspected malingerers were described. METHOD: A total of 17 general practitioners in nine different BMTCs in different regions of Turkey constitute the universe of this descriptive study. In the questionnaire, there were a total of 30 questions about the descriptive characteristics of the participants and their attitudes and behaviours towards malingering. Informed consent form and a questionnaire were applied through the intranet via participants' emails. In the study, 15 physicians were reached with a response rate of 88.2%. RESULTS: All of the physicians suspected malingering in some of the soldiers who were examined. A total of 80% of the physicians (n=12) suspected malingering in at least 10% of the patients they examined. Only 13.3% of the physicians (n=2) had officially diagnosed a case of malingering in the last training period. All of the participants stated that they did not report the official decision for every soldier suspected of malingering. Instead of reporting official decision for malingering, the military physicians apply alternative procedures for suspected malingerers. CONCLUSIONS: In countries where the military service is compulsory, prevalence of malingering is estimated to be higher (approximately 5-25%). The problem of malingering is often underestimated due to the fact it is usually overlooked. Malingering remains a problem for the entire military healthcare system, due to the difficulties in exact diagnosis. Therefore, it can be useful to take some practical administrative measures for the soldiers who are prone to malingering, in order to discourage the behaviour. PMID- 27278969 TI - Medicine and literature. PMID- 27278968 TI - Should early amputation impact initial fluid therapy algorithms in burns resuscitation? A retrospective analysis using 3D modelling. AB - AIMS: While the epidemiology of amputations in patients with burns has been investigated previously, the effect of an amputation on burn size and its impact on fluid management have not been considered in the literature. Fluid resuscitation volumes are based on the percentage of the total body surface area (%TBSA) burned calculated during the primary survey. There is currently no consensus as to whether the fluid volumes should be recalculated after an amputation to compensate for the new body surface area. The aim of this study was to model the impact of an amputation on burn size and predicted fluid requirement. METHODS: A retrospective search was performed of the database at the Queen Elizabeth Hospital Birmingham Regional Burns Centre to identify all patients who had required an early amputation as a result of their burn injury. The search identified 10 patients over a 3-year period. Burn injuries were then mapped using 3D modelling software. BurnCase3D is a computer program that allows accurate plotting of burn injuries on a digital mannequin adjusted for height and weight. Theoretical fluid requirements were then calculated using the Parkland formula for the first 24 h, and Herndon formula for the second 24 h, taking into consideration the effects of the amputation on residual burn size. RESULTS AND CONCLUSIONS: This study demonstrated that amputation can have an unpredictable effect on burn size that results in a significant deviation from predicted fluid resuscitation volumes. This discrepancy in fluid estimation may cause iatrogenic complications due to over-resuscitation in burn-injured casualties. Combining a more accurate estimation of postamputation burn size with goal-directed fluid therapy during the resuscitation phase should enable burn care teams to optimise patient outcomes. PMID- 27278970 TI - Transmission electron microscopy study on the effects of the ultrasound contrast agent Levovist on hepatic cells. AB - PURPOSE: The Ultrasound Equipment and Safety Committee of The Japan Society of Ultrasonics in Medicine performed experiments to confirm whether contrast enhanced ultrasonography damages liver cells. METHODS: Rats were injected with 0.1 ml of 300 mg/ml ultrasound contrast agent (UCA). Diagnostic ultrasound pulses with a center frequency of 6 MHz and a mechanical index of 1.9 were applied to rat livers with a water bag as a coupler to maintain a distance of 2-6 cm between the ultrasound probe surface and the liver. Contrast-enhanced ultrasonography was carried out for 10 s to visualize the entire liver. Then, specimens of liver tissue were fixed using two types of fixation: immersion and perfusion fixation. RESULTS: Although some variations were found in electron micrographs of liver tissue fixed using immersion fixation, none of three blinded readers found any significant differences between micrographs of liver tissue from rats receiving UCA with sonication and those from sham-treated control rats. Changes observed were not thought to be group-specific but instead due to differences between individual rats. When the livers were fixed using perfusion fixation and the hepatic vein was cut after injection of physiological saline for perfusion, a large number of vacuoles >=2 MUm in diameter were observed. This finding suggested that hepatic cell damage observed in this study was caused by high perfusion pressure during the liver fixation process rather than by sonication with UCA. CONCLUSION: Blinded readings of electron micrographs showed no clear evidence that the use of Levovist in ADI mode ultrasonography causes significant damage to liver tissue. PMID- 27278971 TI - Comparing the in vivo sonodynamic effects of dual- and single-frequency ultrasound in breast adenocarcinoma. AB - INTRODUCTION: Dual-frequency ultrasound has recently been shown to extensively enhance the acoustic cavitation yield in water. METHODS: In this study, the in vivo antitumor effect of simultaneous, dual-frequency ultrasound at low-level intensity (I SATA = 2 W/cm(2) for 1 MHz and I SATA = 0.2 W/cm(2) for 150 kHz) in combination with an intravenous injection of 5 mg/kg hematoporphyrin (Hp) was investigated in a model of breast adenocarcinoma in Balb/c mice. Seventy-one tumor-bearing mice were divided into nine treatment groups: control, sham, Hp injection, and single- and dual-frequency sonication in the presence and absence of Hp. The tumor growth delay was then calculated based on the tumor volume at various times after treatment using the following parameters: relative volume percent, [Formula: see text] and [Formula: see text] times (to reach five and two times the initial volume), percent of tumor growth inhibition ratio, and survival period. RESULTS: Our results showed no significant difference between the 150 kHz and 1 MHz single-frequency groups when compared with the sham group after 9 days of treatment (p > 0.05). However, treatment with dual-frequency ultrasound significantly delayed tumor growth when compared with the sham group (p < 0.05) after 9 days of treatment. Furthermore, in vivo experiments showed that combined dual-frequency sonication controlled tumor growth more effectively than single frequency sonication. Evaluation of the therapeutic effects of single- and dual frequency ultrasound in sonodynamic therapy revealed that treatment with the combination of dual-frequency ultrasound and Hp resulted in a significant reduction in the relative volume percent of tumors after 3 days of treatment (p < 0.05) compared with the controls. Additionally, the T 5 time and the survival period in the group treated with the combination therapy was significantly longer than those in all the other groups (p < 0.05). These findings were further verified histopathologically. CONCLUSION: In conclusion, our results reveal that sonodynamic therapy using dual-frequency ultrasound is able to extend the survival time of animals compared with single-frequency sonication. PMID- 27278972 TI - Small calcification indicator in ultrasonography using correlation of echoes with a modified Wiener filter. AB - PURPOSE: The purpose of this study is to improve the calcification depiction ability in ultrasonography using correlation of echoes with a modified Wiener filter. METHODS: The waveform of an ultrasound pulse changes when it passes through the location of a calcification. Since the change in echo waveform caused by a calcification decreases the correlation of waveforms in adjacent scan lines, we have proposed a calcification depiction method using the decorrelation of echoes. However, the low signal-to-noise ratio of echoes also decreases the correlation of the echoes. In this study, we employ the correlation of echoes with a modified Wiener filter to suppress the effect of noise, as an indicator of a calcification. RESULTS: The proposed calcification indicator depicted copper cylindrical rods 0.2 mm in size at a depth of 2 cm with a sensitivity of 80% and a positive predictive value of 80%, despite being hardly depicted at all on B mode ultrasound imaging. CONCLUSION: This study suggests the potential of the proposed method to improve the performance of calcification depiction by ultrasound devices. PMID- 27278973 TI - Experimental study on temperature rise of acoustic radiation force elastography. AB - INTRODUCTION: Acoustic radiation force (ARF) elastography is potentially useful for imaging the elasticity of human tissue. Because a "push wave" that is used to generate ARF is a long burst wave comparable to that used in regular clinical imaging, detailed investigation of its safety is required. MATERIALS AND METHODS: We focus on the transient temperature rise in the far field, where the beam paths are overlapped. Soft tissue mimicking a phantom and bone samples were exposed to a 2-MHz plane wave for 20 s. The temperature rises in the far field were measured using a thermocouple. The temperature rises at 1 ms, the time required for the displacement measurement, were estimated by fitting the experimental results. The results showed that the thermosensitivity of the bone was 36 times higher than that of the phantom, and the use of a repeated push wave may have exceeded the allowable maximum temperature rise, 1 degrees C, on the bone surface. CONCLUSION: In conclusion, the imaging area, including the path of the push wave, should be carefully checked and the time interval for consecutive use should be adjusted to prevent thermal risk on the surface of the bone. PMID- 27278974 TI - Impact of transcatheter closure of atrial septal defects on cardiac function. AB - PURPOSE: The purpose of this study was to investigate the effects of transcatheter closure of atrial septal defects (ASD) on left ventricular function. METHODS: Conventional and three-dimensional echocardiographic methods (3D) were performed in 20 patients who underwent ASD closure. Diastolic and systolic volumes (LVVd and LVVs) and ejection fractions (EF) were determined by 3D methods. Doppler and tissue Doppler indices were also measured before and 1 day after the procedure. We determined the predictors of patients with a mitral early Doppler/tissue Doppler velocity ratio (E/E') >=8 after closure. RESULTS: Ejection fraction decreased (from 70 +/- 8 to 63 +/- 8%, p = 0.005) after the procedure because of an equivalent increase in LVVs and LVVd maintaining the same cardiac output. Among the echocardiographic variables before ASD closure that correlated with E/E' after closure, the receiver operating characteristic curve of E' gave the largest area under the curve with E' of 12.2 cm/s as the best predictor of patients with E/E' >=8 after ASD closure. CONCLUSION: Atrial septal defect closure decreased EF on the surface, thereby maintaining the same stroke volume and cardiac output. Patients with diastolic dysfunction before closure might have a higher risk of developing congestive heart failure after ASD closure. PMID- 27278975 TI - Primary echocardiographic results of the Carpentier-Edwards Perimount Magna. AB - PURPOSE: The aim of this study was to investigate the primary echocardiographic results of aortic valve replacement using 21- and 19-mm Carpentier-Edwards Perimount Magna bioprosthesis aortic xenografts in patients with small aortic annulus. METHODS: Twenty patients (mean body surface area 1.63 +/- 0.16 m(2)) underwent aortic valve replacement between June 2008 and December 2009. Eight and 12 patients received 21- and 19-mm Magna bioprostheses, respectively. After 12 months, hemodynamic data were obtained by echocardiography to estimate the prosthesis-patient mismatch. RESULTS: At follow-up, significant decreases in peak and mean left ventricular aortic pressure gradients were observed in the 12 patients with aortic stenosis (P < 0.05). Regression of the left ventricular mass was observed in all the patients (P < 0.05). The mean measured effective orifice area (EOA) and EOA index (EOAI) were 1.61 +/- 0.28 cm(2) and 0.99 +/- 0.16 cm(2)/m(2), respectively. Prosthesis-patient mismatch (EOAI <=0.85) was documented in three patients. CONCLUSION: The primary echocardiographic findings suggested that the hemodynamic performance of the 19- and 21-mm Carpentier Edwards Perimount Magna bioprostheses was satisfactory in the patients with a small aortic annulus. PMID- 27278977 TI - Pseudoaneurysm with left-to-right shunt in a patient with myocardial infarction: evaluation by three-dimensional echocardiography. AB - It is often difficult to noninvasively differentiate a post-infarction left ventricular (LV) pseudoaneurysm from a post-infarction true aneurysm. A 66-year old woman with a past history of inferior acute myocardial infarction was admitted to our hospital because of acute decompensated heart failure. Two dimensional transthoracic echocardiography showed an aneurysm with a narrow orifice in the inferoposterior basal area. The pulmonary to systemic flow ratio (Q p/Q s) was 2.2:1, which corresponded to moderate left-right shunting. Three dimensional transesophageal echocardiography (3D-TEE) showed the orifice in the perforated right ventricular basal area with a color jet through the orifice from the LV to the right ventricle. Collectively, based on the 3D-TEE findings, we diagnosed the case as inferoposterior pseudoaneurysm with a left-to-right shunt caused by myocardial infarction. PMID- 27278976 TI - Contrast-enhanced ultrasonography with SonazoidTM for the evaluation of bowel ischemia. AB - PURPOSE: To determine the usefulness of contrast-enhanced ultrasonography with the contrast agent SonazoidTM for the detection of bowel ischemia. METHODS: From March 2007 to February 2009, 65 patients (35 men and 30 women, mean age 70.4 +/- 16.1 years) were enrolled. Fifty-three patients complained of acute abdominal pain with small bowel dilatation (n = 40) or reduced bowel peristalsis (n = 13). Twelve patients were clinically suspected of having bowel ischemia. After SonazoidTM injection, bowel segments were scanned using harmonic imaging, and the signal intensities were classified as normal or diminished. The definitive diagnosis was confirmed by surgery in 30 patients, autopsy in 6, endoscopy in 3, angiography in 1, and clinical follow-up in 25. RESULTS: All 50 patients with normal signal intensities were confirmed not to have bowel ischemia. In the 15 patients with diminished signal intensities, 14 patients were confirmed to have bowel ischemia, resulting in an overall sensitivity of 100% [95% confidence interval (CI) 80.7-100%], a specificity of 98% [95% CI 89.5-99.9%], a positive predictive value of 93% (95% CI 68.1-99.8%), and a negative predictive value of 100% (95% CI 94.1-100%). CONCLUSION: Contrast-enhanced ultrasonography with SonazoidTM is a highly sensitive and specific method for the diagnosis of bowel ischemia. PMID- 27278978 TI - Left atrial myxoma mimicking papillary fibroelastoma. AB - A 67-year-old woman was referred to our hospital with a diagnosis of deep vein thrombosis due to surgery for left patellar fracture. Deep vein thrombosis resolved with thrombolytic therapy. Transthoracic echocardiogram revealed a mobile left atrial tumor. Transesophageal echocardiography showed a fragile tumor with multiple fronds, implying a papillary fibroelastoma. Because this patient had a history of cerebral embolism, urgent surgery was scheduled. The excised tumor showed a sea anemone-like appearance in saline, which was similar to that of a papillary fibroelastoma. However, histological examination revealed the features of a myxoma and not papillary fibroelastoma. Herein, we illustrate a very rare case of left atrial myxoma with papillary fibroelastoma-like features in terms of both echocardiographic and gross findings. PMID- 27278979 TI - Abnormal first-trimester fetal nuchal translucency and amniotic band syndrome. AB - We report a case of amniotic band syndrome diagnosed prenatally by serial sonographic examinations. Our initial sonographic image showed a large fetal nuchal translucency (NT) at 12 weeks' gestation. Repeated fetal ultrasound images revealed an amniotic band and right upper limb anomaly. Fetal MRI at 19 weeks' gestation revealed right forearm hypoplasia and pseudosyndactyly. The fetus was prenatally diagnosed with amniotic band syndrome and was suspected of having severe functional impairment of the deformed limb. The parents decided to terminate the pregnancy at 21 weeks' gestation. In fetuses with aneuploidy and various structural and genetic abnormalities, the NT thickness is increased in the first trimester. As far as we are aware, this is the first case report of increased NT and limb anomaly associated with amniotic band syndrome. In chromosomally normal fetuses with increased NT, intensive sonographic follow-up should provide grounds for a precise antenatal diagnosis. PMID- 27278980 TI - Neonatal periventricular leukomalacia without evidence of twin-to-twin transfusion syndrome following discordance in nuchal translucency: a case report. AB - We describe a case of neonatal periventricular leukomalacia (PVL) without evidence of twin-to-twin transfusion syndrome (TTTS) following discordance in nuchal translucency (NT). A 34-year-old woman with monochorionic twins after in vitro fertilization and embryo transfer was referred to our hospital. At gestational week 11, fetus A showed increased NT (7.0 mm) and normal crown-rump length (CRL) (34.3 mm). Fetus B had normal values, with a NT of 1.3 mm and a CRL of 32.3 mm. Both twins maintained growth throughout pregnancy, with no evidence of TTTS. During the antepartum period, daily fetal heart rate monitoring showed a reassuring pattern. Cesarean delivery was performed in gestational week 32. Neonates A and B weighed 2,071 and 1,617 g, respectively (discordancy rate 21.9%), each with an Apgar score of 8 at 1 min. Soon after birth, brain ultrasonography of neonate A revealed high-echoic periventricular lesions bilaterally, and brain magnetic resonance imaging on day 7 revealed PVL. Neonate B showed completely unremarkable results. PMID- 27278981 TI - Enlarging amniotic fluid 'sludge' in preterm labor associated with severe course of sepsis and recurrent tension pneumothorax in the infant. AB - Amniotic fluid 'sludge' (AFS) is defined as the presence of dense aggregates of hyperechogenic material in close proximity to the internal cervical os. The presence of AFS is an independent risk factor for impending preterm delivery, histological chorioamnionitis, and microbial invasion of the amniotic cavity in patients with spontaneous preterm labor with intact membranes, and preterm prelabor rupture of membranes. We describe a case showing enlarging AFS on transvaginal ultrasound in a patient with impending preterm labor, followed by chorioamnionitis and emergency cesarean section at 28 weeks of gestation, resulting in a severe course of sepsis and recurrent tension pneumothorax in the infant. Such a case has not been reported as far as we know. Based on our case, sonographic findings of enlarging AFS may be a predictor of severe neonatal outcomes in a case with preterm labor even though the maternal symptoms of inflammation are not obvious. PMID- 27278982 TI - Isolated hepatic metastasis with hepatic venous invasion and tumor thrombus in right atrium. PMID- 27278983 TI - Sonographic diagnosis of Fournier's gangrene: a rare surgical emergency. AB - Early diagnosis of life-threatening Fournier's gangrene, a rare surgical emergency, is essential. Detection of gas within the swollen scrotal skin by ultrasonography (US) is of great help in patients with equivocal physical examination findings. PMID- 27278985 TI - Inquiries and challenges bring joy and confidence. PMID- 27278984 TI - Ultrasonography findings in temporal arteritis. PMID- 27278986 TI - Therapeutic potential of low-intensity ultrasound (part 1): thermal and sonomechanical effects. AB - In this first part of the review, we will focus on and discuss various aspects of low-intensity ultrasound (US), with emphasis on mild thermal effects, apoptosis induction, and sonomechanical effects. Mild thermal effects of US have been commonly applied to physical therapy. Though US has clear beneficial effects, the advantage of using US over other heating modalities remains unclear. US has also been used in vivo and clinically in the treatment of wounds and fractures, with promising results. On the biomolecular level, studies have shown that US can induce apoptosis and that certain conditions can provide optimal apoptosis induction. As to potential therapeutic applications, in addition to the thermal and other physical effects, apoptosis induction by US may offer direct and rapid treatment of tumors or cancer tissues. Technological advances and rapidly accelerating research in this field are providing an ever-increasing array of therapeutic options for lowintensity US. PMID- 27278987 TI - Therapeutic potential of low-intensity ultrasound (part 2): biomolecular effects, sonotransfection, and sonopermeabilization. AB - Part one of this review focused on the thermal and mechanical effects of low intensity ultrasound (US). In this second and final part of the review, we will focus on and discuss various aspects of low-intensity US, with emphasis on the biomolecular effects, US-mediated gene transfection (sonotransfection), and US mediated permeabilization (sonopermeabilization). Sonotransfection of different cell lines in vitro and target tissues in vivo have been reported. Optimization experiments have been done and different mechanisms investigated. It has also been found that several genes can be up-regulated or down-regulated by sonication. As to the potential therapeutic applications, systemic or local sonotransfection might also be a safe and effective gene therapy method in effecting the cure of local and systemic disorders. Gene regulation of target cells may be utilized in modifying cellular response to a treatment, such as increasing the sensitivity of diseased cells while making normal cells resistant to the side effects of a treatment. Advances in sonodynamic therapy and drug sonopermeabilization also offer an ever-increasing array of therapeutic options for low-intensity US. PMID- 27278988 TI - Contributions of mechanical and sonochemical effects to cell membrane damage induced by single-shot pulsed ultrasound with adjacent microbubbles. AB - PURPOSE: The objective was to investigate the contributions of mechanical effects due to kinetic force induced by the dynamic behavior of microbubbles and sonochemical effects due to free radicals produced by inertial cavitation to cell membrane damage under sonoporation conditions in which cells with adjacent microbubbles were irradiated with single-shot pulsed ultrasound. METHODS: The free radical scavenger cysteamine was used to control the occurrence of sonochemical effects, and the ratios of cells with membrane damage to intact cells were compared in the presence and absence of cysteamine. To determine the optimal dose of cysteamine, free radical production on exposure to burst pulse ultrasound was investigated using KI-starch solutions with different concentrations (0-5 mM) of cysteamine. High-speed observation of the dynamic behavior of Levovist microbubbles during ultrasound exposure was also carried out in the presence and absence of cysteamine, and the difference in the ratios of the maximum bubble diameter to the initial diameter was evaluated. Next, human prostate cancer cells with adjacent Levovist microbubbles were exposed to single shot pulsed ultrasound with a center frequency of 1 MHz, a peak negative pressure of 1.1 MPa, and a pulse width of 3 MUs, and the percentages of cells with membrane damage were evaluated by fluorescent microscopy using propidium iodide in the presence and absence of cysteamine. RESULTS: It was confirmed that cysteamine at a concentration of 5 mM completely suppressed sonochemical effects without causing a change in the dynamic response of microbubbles to pulsed ultrasound. The percentages of cells with membrane damage in the presence and absence of cysteamine (5 mM) were 10.3% +/- 4.1% (n = 13) and 8.7% +/- 3.9% (n = 9), respectively. No significant difference was found (P = 0.36). CONCLUSION: The results indicate that cell membrane damage induced by single-shot pulsed ultrasound with adjacent microbubbles was due mainly to mechanical effects, not to sonochemical effects. PMID- 27278989 TI - Sequential changes in rat femoral artery blood flow and tissue degeneration after exposure to high-intensity focused ultrasound. AB - PURPOSE: The purpose of this study was to investigate the sequential changes in rat artery blood flow and tissue degeneration after exposure to high-intensity focused ultrasound (HIFU) in vivo. METHODS: HIFU was applied through the skin to the femoral artery of Sprague-Dawley rats. The peak intensities used were 530, 1080, 2750, and 4300 W/cm(2). After exposure, we measured the peak systolic velocity (PSV) in the artery every 1 min until the velocity stabilized. The vessel was resected and examined histologically 7 days after exposure. RESULTS: PSV was not significantly affected by HIFU exposure at 530 W/cm(2). PSV increased immediately after HIFU exposure at intensities of 1080 and 2750 W/cm(2). PSV after HIFU exposure at 1080 W/cm(2) fell to the control level within minutes; however, PSV increased immediately after HIFU exposure at 2750 W/cm(2) and then decreased slowly but remained at a higher level than the control for 15 min. On HIFU exposure at 4300 W/cm(2), the target artery was completely occluded. Histological studies 7 days after HIFU exposure demonstrated that exposure at 530 and 1080 W/cm(2) induced vacuolar degeneration in the tunica media of the femoral artery in rats; exposure to HIFU at 2750 and 4300 W/cm(2) resulted in strong necrotic degeneration in the tunica media. These histological changes were more marked than those found immediately after HIFU exposure. Organized thrombus formation was observed only for HIFU exposure at 4300 W/cm(2). CONCLUSION: Sequential changes in arterial blood flow after HIFU exposure vary with the intensity, and the histological changes in arterial tissue progress over time. These phenomena should be considered when HIFU is clinically applied to achieve arterial occlusion. PMID- 27278990 TI - Contrast-enhanced ultrasonography with Sonazoid for evaluation of renal microcirculation. AB - PURPOSE: The renal medullary microcirculation plays an important role in regulating sodium and water excretion, and its impairment is closely associated with various renal diseases. Contrast-enhanced ultrasonography (CEUS) using Sonazoid has not yet been reported as a method for evaluating the renal microcirculation; consequently, this study was carried out to reveal the characteristics of renal microcirculation using CEUS with Sonazoid. METHODS: CEUS was performed on three healthy volunteers after they had fasted for at least 6 h. A GE LOGIQ7 ultrasound unit was used with a 2.0- to 5.5-MHz convex probe. Within approximately 1 min of intravenous injection of 0.0050 ml/kg Sonazoid, contrast images of the right kidney were acquired using a coded phase-inversion mode. Time intensity curves were calculated for the cortex and medulla. RESULTS: Peak contrast intensity was significantly higher in the cortex (-56.4 +/- 1.9 dB) than in the medulla (-66.7 +/- 1.7 dB; P < 0.005). Peak times were significantly earlier in the cortex (17.4 +/- 3.7 ms) than in the medulla (28.8 +/- 6.3 ms; P < 0.05). CONCLUSION: CEUS using Sonazoid enables differentiation between the cortical and medullary microcirculation and is useful in clarifying renal pathophysiology and pharmacology. PMID- 27278991 TI - Multiple anechoic hepatic nodules in a patient with malignant lymphoma: report of a case with an emphasis on B-mode sonograms. AB - We present a case of hepatic malignant lymphoma (ML) in which the hepatic ML nodules were imaged as round anechoic nodules with posterior echo enhancement, mimicking hepatic cysts on B-mode ultrasonography (US). However, the boundary echo between the nodules and the surrounding hepatic tissue seemed to be less distinct than that of a hepatic cyst. Contrast-enhanced US showed the nodules to be hypervascular, which ruled out the possibility of hepatic cysts. Our observation stresses the importance of boundary echo for the diagnosis of hepatic ML on B-mode US. We also offer a possible explanation for this phenomenon. PMID- 27278992 TI - Three-dimensional sonographic features of a fetus with Wolf-Hirschhorn syndrome. AB - We present a case of fetal Wolf-Hirschhorn syndrome diagnosed by conventional two dimensional and three-dimensional ultrasonography. Conventional two-dimensional ultrasonography revealed a diaphragmatic hernia, nuchal edema, and suspected hypospadias. Three-dimensional ultrasonography clearly showed a flattening of the face, a high forehead, a broad nasal bridge continuing to the forehead, exophthalmos, and micrognathia (resembling the appearance of a Greek warrior helmet), but conventional two-dimensional ultrasonography did not depict these findings. Prenatal chromosomal analysis confirmed the diagnosis of Wolf Hirschhorn syndrome [46XY, del(4)(p15.2)]. Here we demonstrate how three dimensional ultrasonography provided a novel visual depiction of the facial dysmorphism, which helped substantially in prenatal counseling. PMID- 27278993 TI - A case of dual ectopic thyroid accompanied by positive antithyroid antibodies. AB - Ectopic thyroid tissue is an uncommon congenital aberration that is seldom present at two different sites simultaneously. The patient was a 32-year-old woman with dual ectopic thyroid accompanied by positive antithyroid antibodies. The simultaneous occurrence of dual ectopic thyroid and positive antithyroid antibodies has been documented in only two cases: the case discussed here and one previous case. The cervical ectopic thyroid was followed up by ultrasound, which showed an increase in the size of the lesion and an internal echo texture that became slightly heterogeneous after the patient had her second child. We speculated that these changes resulted from the changes in hormone demand brought on by pregnancy and parturition. PMID- 27278994 TI - Primary small-cell carcinoma of the breast: a case report. AB - We report a case of small-cell carcinoma of the breast. The patient was a 54-year old Japanese woman with a left breast mass. Mammography revealed a 1.2-cm microlobulated mass with partially ill-defined borders. Ultrasonography disclosed a hypoechoic mass measuring 1.8 * 1.2 * 1.2 cm with heterogeneous internal echoes and partially ill-defined borders. The shape of the mass was round and taller than it was wide in the orthogonal section to the longest axis of the mass. These imaging findings suggested a malignant tumor. Fine-needle aspiration cytology of the tumor also suggested a ductal carcinoma. Breast-conserving surgery was performed with axillary sentinel lymph node biopsy. A diagnosis of small-cell carcinoma of the breast was made based on the histologic and immunohistochemical findings. This rare breast tumor has been reported to be aggressive and associated with a poor prognosis; however, our patient is currently well and has had no clinical recurrence of the disease after 5 years of follow-up without radiotherapy or chemotherapy. Therefore, the prognosis may be better if the tumor is detected early and there is an absence of lymph node metastasis. PMID- 27278995 TI - Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy. PMID- 27278996 TI - Gastric carcinoma with portal tumor thrombus. PMID- 27278999 TI - Dual modification of biomolecules. AB - With the advent of novel bioorthogonal reactions and "click" chemistry, an increasing number of strategies for the single labelling of proteins and oligonucleotides have emerged. Whilst several methods exist for the site selective introduction of a single chemical moiety, site-selective and bioorthogonal dual modification of biomolecules remains a challenge. The introduction of multiple modules enables a plethora of permutations and combinations and can generate a variety of bioconjuguates with many potential applications. From de novo approaches on oligomers to the post-translational functionalisation of proteins, this review will highlight the main strategies to dually modify biomolecules. PMID- 27278998 TI - Establishment and characterization of a highly immunogenic human renal carcinoma cell line. AB - Renal cell carcinoma (RCC) is the most common kidney cancer, and accounts for ~3% of all adult malignancies. RCC has proven refractory to conventional treatment modalities but appears to be the only histological form that shows any consistent response to immunotherapeutic approaches. The development of a clinically effective vaccine remains a major strategic target for devising active specific immunotherapy in RCC. We aimed to identify a highly immunogenic antigenic format for immunotherapeutic approaches, so as to boost immune responses in RCC patients. We established and cloned an immunogenic cell line, RCC85#21 named Elthem, which was derived from a non-aggressive and non-metastatic clear cell carcinoma. The cell line characterization was performed by genomics (real-time PCR, genome instability), proteomics (two dimensional electrophoresis, mass spectro-metry) and immunological analysis (mixed lymphocytes tumor cell cultures). Real-time PCR confirmed the RCC85#21 cell expression of tumor antigens and cytokine genes. No difference in microsatellite instability (MSI) in RCC85#21 cell line was found as compared to control, loss of heterozygosity was observed in the RCC85#21 clone, but not in the renal cancer cell lines from which it was generated. The image analysis of RCC85#21 by two-dimensional gels showed 700+/-26 spots and 119 spots were identified by mass spectrometry analysis. RCC85#21 promoted a significant RCC-specific T cells activation by exhibiting a cytotoxic phenotype after mixed lymphocyte and tumor cell cultures. CD8+ T cells isolated from RCC patients displayed an elevated reactivity against RCC85#21 and efficiently lysed the RCC85#21 clone. The RCC85#21 immunogenic cell line will be suitable for immune stimulation. The identification of novel tumor associated antigens will allow the evaluation of the immune response in vitro and, subsequently, in vivo paving the way for new immunotherapeutic strategies in the RCC setting. PMID- 27279000 TI - Elimination of urogenital schistosomiasis in Iran: past history and the current situation. AB - In recent years, through a national programme for schistosomiasis control, this infection has been eliminated from Iran. The aim of this study was to report the process of significant decrease of urogenital schistosomiasis in southwestern Iran. During national programme surveillance for urogenital schistosomiasis control which was implemented by Centres for Disease Control and Prevention (CDC) of Khuzestan province from 1975 to 2013, more than 1.3 million urine samples were taken from inhabitants of high risk foci. All urine samples were gathered between 10:00 a.m and 02:00 p.m and, after centrifuging, specimens were tested under optical microscope in order to detect Schistosoma haematobium eggs. Data analysis was performed using SPSS 18 software. In this retrospective study significant reduction was seen in number of infections between 1975 and 2013. During the years 1975-1980, 1981-1990 and 1991-2000 there were 1582, 761 and 79 cases of S. haematobium, respectively. In 2001 only one case was reported from Ahvaz and indeed this was the last case of urogenital schistosomiasis in Khuzestan and of course, in Iran. Prevalence from 1.064% between 1975 and 1980 slumped to 0% in 2012-2013. During several projects for surveillance of urogenital schistosomiasis, selective population chemotherapy, snail control, population education, environmental improvement, etc were carried out throughout the surveillance period. According to elimination of S. haematobium in Khuzestan province, the only endemic region of Iran, control of disease, especially the campaign with intermediate host snails should be continued. Iran can be a successful model for countries suffering from this disease. PMID- 27279001 TI - Perceptions of cancer treatment decision making among American Indians/Alaska Natives and their physicians. AB - OBJECTIVE: American Indian/Alaska Native (AI/AN) patients are significantly less likely than non-Hispanic whites to receive guideline-concordant cancer care. Our objective was to examine cancer treatment decision making among AI/AN patients and their providers. METHODS: From 2011 to 2014, AI/AN cancer patients and their surgeons were identified through a hospital registry in Washington State. Patients were invited to participate in a mailed survey that queried socio demographics, cultural affiliation, everyday perceived discrimination, and trust in providers. Both patients and surgeons were queried about decision-making quality (collaboration and satisfaction). The primary outcome was association between patient and provider assessments of decision-making quality. The secondary outcome was non-adherence to treatment. RESULTS: Forty-nine patients (62% response rate) and 14 surgeons (37% response rate) returned surveys. Half of patients had not completed high school; 41% were living in poverty. Half of patients reported a strong tribal affiliation and most reported experiencing some form of discrimination. Patients endorsed high trust in surgeons and a high quality decision-making process; and surgeons' rated decision-making quality even more highly than patients did in every domain. Non-adherence to treatment recommendations was common (26%) and was significantly associated with lower patient-reported collaboration and satisfaction with decision making. CONCLUSIONS: Given the importance of adherence to cancer treatment for survival, the many non-clinical reasons for non-adherence, and the currently demonstrated association between decision-making quality and adherence, it would be worthwhile to investigate how to increase AI/AN patient satisfaction with decision making and whether improving satisfaction yields improved adherence to the cancer treatment plan. Copyright (c) 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd. PMID- 27279002 TI - Thigh magnetic resonance imaging for the evaluation of disease activity in patients with idiopathic inflammatory myopathies followed in a single center. AB - INTRODUCTION: In patients with idiopathic inflammatory myopathies (IIM), magnetic resonance imaging (MRI) has been proposed as a useful tool for diagnosis and follow-up. It may identify muscle inflammation (edema) and fatty infiltration for evaluation of disease activity and damage. Little information is available on the role of MRI in assessment of large cohorts of adult patients with IIM. METHODS: Fifty-one patients underwent MRI of the thigh muscles, laboratory tests, and clinical evaluation, including Physician Global Assessment (PGA) of myositis activity and the Manual Muscle Test 8 (MMT8). RESULTS: Muscle edema correlated significantly with creatine kinase values (P = 0.017) and PGA (P < 0.001). A significant correlation between edema and MMT8 values (P = 0.025) was observed when patients with muscle fatty infiltration were excluded. With respect to clinical diagnosis, the sensitivity of MRI was 92.3%, and specificity was 83.3%. CONCLUSIONS: MRI appears to provide additional information that complements clinical and biochemical examinations. Muscle Nerve 54: 666-672, 2016. PMID- 27279004 TI - Factors associated with quality of life in Arab patients with heart failure. AB - The aim of this study was to examine the relationships of demographic characteristics, medical variables and perceived social support with quality of life (QOL) in Arab patients with heart failure. A cross-sectional study was conducted to identify factors associated with QOL in Arab patients with heart failure. Participants with heart failure (N = 99) were enrolled from a nonprofit hospital and an educational hospital. Data were collected on QOL using the Short Form-36 survey. Perceived social support was measured with the Medical Outcomes Study Social Support Survey. The majority of the patients reported significant impairment in QOL as evidenced by subscale scored. Left ventricular ejection fraction was the strongest correlate of most QOL domains. Tangible support was significantly associated with most QOL domains. Other social support dimensions were not significantly related to QOL domains. Most patients with heart failure had significant disrupting pain and limitations in performing activities which interfered with their usual role. Due to the importance of understanding QOL and its determinants within the context of culture, the outcomes of this study may provide valuable guidance to healthcare providers in Arabic countries as well as Western society in caring for these patients. Further studies are needed to explore the relationship between social support and QOL among patients with heart failure in the Arabic culture. PMID- 27279003 TI - Association between Body Condition Score and Cancer Prognosis in Dogs with Lymphoma and Osteosarcoma. AB - BACKGROUND: In humans and rodents obesity appears to promote some cancers by increasing incidence, tumor aggressiveness, recurrence, and fatality. However, the relationship between obesity and cancer in dogs has not been thoroughly evaluated. HYPOTHESIS/OBJECTIVES: Whether body condition score (BCS) at the time of lymphoma (LSA) or osteosarcoma (OSA) diagnosis in dogs is predictive of survival time (ST) or progression-free interval (PFI). We hypothesized that an overweight body state at the time of cancer diagnosis would be associated with negative outcomes. ANIMALS: Dogs with LSA (n = 270) and OSA (n = 54) diagnosed and treated between 2000 and 2010. METHODS: Retrospective case review. Signalment, body weight, BCS, cancer diagnosis and treatment, relevant clinicopathologic values, and survival data were collected. Dogs were grouped by BCS (underweight, ideal, and overweight) and ST and PFI were compared. RESULTS: Overall, 5.5% of dogs were underweight, 54.0% were ideal weight, and 40.4% were overweight at diagnosis. Underweight dogs with LSA had shorter ST (P = .017) than ideal or overweight dogs. BCS was not associated with ST for OSA (P = .474). Progression-free interval did not differ among BCS categories for either cancer. CONCLUSIONS AND CLINICAL IMPORTANCE: Obesity was not associated with adverse outcomes among dogs with LSA or OSA in this retrospective study; however, being underweight at the time of diagnosis of LSA was associated with shorter survival. More research is needed to elucidate the relationship between excessive body weight and cancer development and progression in dogs. PMID- 27279005 TI - Directed percolation identified as equilibrium pre-transition towards non equilibrium arrested gel states. AB - The macroscopic properties of gels arise from their slow dynamics and load bearing network structure, which are exploited by nature and in numerous industrial products. However, a link between these structural and dynamical properties has remained elusive. Here we present confocal microscopy experiments and simulations of gel-forming colloid-polymer mixtures. They reveal that gel formation is preceded by continuous and directed percolation. Both transitions lead to system-spanning networks, but only directed percolation results in extremely slow dynamics, ageing and a shrinking of the gel that resembles synaeresis. Therefore, dynamical arrest in gels is found to be linked to a structural transition, namely directed percolation, which is quantitatively associated with the mean number of bonded neighbours. Directed percolation denotes a universality class of transitions. Our study hence connects gel formation to a well-developed theoretical framework, which now can be exploited to achieve a detailed understanding of arrested gels. PMID- 27279006 TI - Reovirus intermediate subviral particles constitute a strategy to infect intestinal epithelial cells by exploiting TGF-beta dependent pro-survival signaling. AB - Intestinal epithelial cells (IECs) constitute the primary barrier that separates us from the outside environment. These cells, lining the surface of the intestinal tract, represent a major challenge that enteric pathogens have to face. How IECs respond to viral infection and whether enteric viruses have developed strategies to subvert IECs innate immune response remains poorly characterized. Using mammalian reovirus (MRV) as a model enteric virus, we found that the intermediate subviral particles (ISVPs), which are formed in the gut during the natural course of infection by proteolytic digestion of the reovirus virion, trigger reduced innate antiviral immune response in IECs. On the contrary, infection of IECs by virions induces a strong antiviral immune response that leads to cellular death. Additionally, we determined that virions can be sensed by both TLR and RLR pathways while ISVPs are sensed by RLR pathways only. Interestingly, we found that ISVP infected cells secrete TGF-beta acting as a pro survival factor that protects IECs against virion induced cellular death. We propose that ISVPs represent a reovirus strategy to initiate primary infection of the gut by subverting IECs innate immune system and by counteracting cellular death pathways. PMID- 27279007 TI - Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo. AB - Apigenin (4',5,7-trihydroxyflavone) is a flavone that has been reported to have anti-inflammatory, antioxidant and anti-carcinogenic properties. In this study, we investigated the protective effects of apigenin on skin and found that, in experiments using cells, apigenin restored the viability of normal human dermal fibroblasts (nHDFs), which had been decreased by exposure to ultraviolet (UV) radiation in the UVA range. Using a senescence-associated (SA)-beta-gal assay, we also demonstrate that apigenin protects against the UVA-induced senescence of nHDFs. Furthermore, we found that apigenin decreased the expression of the collagenase, matrix metalloproteinase (MMP)-1, in UVA-irradiated nHDFs. UVA, which has been previously identified as a photoaging-inducing factor, has been shown to induce MMP-1 expression. The elevated expression of MMP-1 impairs the collagen matrix, leading to the loss of elasticity and skin dryness. Therefore, we examined the clinical efficacy of apigenin on aged skin, using an apigenin containing cream for clinical application. Specifically, we measured dermal density, skin elasticity and the length of fine wrinkles in subjects treated with apigenin cream or the control cream without apigenin. Additionally, we investigated the effects of the apigenin-containing cream on skin texture, moisture and transepidermal water loss (TEWL). From these experiments, we found that the apigenin-containing cream increased dermal density and elasticity, and reduced fine wrinkle length. It also improved skin evenness, moisture content and TEWL. These results clearly demonstrate the biological effects of apigenin, demonstrating both its cellular and clinical efficacy, and suggest that this compound holds promise as an anti-aging cosmetic ingredient. PMID- 27279008 TI - Docetaxel-loaded PEG-albumin nanoparticles with improved antitumor efficiency against non-small cell lung cancer. AB - The aim of the present study was mainly to assess the advantage of docetaxel loaded PEG-albumin nanoparticles (PEG-DANPs) against non-small cell lung cancer (NSCLC) compared with the commercial product of docetaxel (Aisu(r)) and docetaxel albumin nanoparticles (DANPs). We made systematic assessments on these three drugs against NSCLC both in vitro and in vivo. Based on our experiments, PEG DANPs showed a dose- and time-dependent efficacy in the in vitro cytotoxicity studies; the tumors growth and the metastases in the livers of NSCLC-bearing nude mice in vivo were reduced dmarkedly by PEG-DANPs, and the PEG-DANP-treated mice had a minimum of weight loss; furthermore, the mice which were treated with PEG DANPs can survive longer than the other groups. In conclusion, the PEG-DANPs have the lowest side-effects, and the highest antitumor and metastases activity of the three drugs, and it may provide an alternative to patients with NSCLC. PMID- 27279009 TI - Usefulness and Pitfalls in Sodium Intake Estimation: Comparison of Dietary Assessment and Urinary Excretion in Chilean Children and Adults. AB - BACKGROUND: High sodium intake has been associated with various noncommunicable disease like hypertension, cardiovascular disease, or stroke. To estimate accurately sodium intake is challenging in clinical practice. We investigate the usefulness and limitations of assessing sodium intake simultaneously by dietary assessment and urinary samples in both children and adults. METHODS: We used a cross-sectional study design inviting 298 Chilean subjects (74 children and 222 adults) aged between 9 and 66 years of both genders. Sodium intake by dietary assessment was obtained from Chilean food composition data, based on FAO tables. Sodium and creatinine excretion were measured in 24-hour urine samples, in all participants. RESULTS: Adequate urinary collection was obtained in 81% of children (59/74) and 61% of adults (135/222). The mean sodium intake by dietary assessment was similar to the sodium excretion in 24 hours (3,121+/-1,153mg/d vs. 3,114+/-1,353mg/24h, P = nonsignificant) in children but was significantly lower (3,208+/-1,284mg/d vs. 4,160+/-1,651mg/24h, P < 0.001) in adults. In both children and adults, sodium intake correlated with urinary sodium excretion (r = 0.456, P < 0.003 and r = 0.390, P < 0.001, respectively). Secondary analyses also suggested that the dietary assessment was more inaccurate in overweight adult subjects. CONCLUSIONS: Our results showed that average sodium intake was higher than recommended in both children and adults (WHO <=2,000mg/d). The sodium intake estimated by dietary assessment correlated with urinary excretion in all subjects, but in obese adults was more inaccurate than in children. Future studies to validate the appropriate test to assess sodium intake by age and nutritional status are warranted. PMID- 27279010 TI - [Formula: see text]Dorsal and ventral visual streams: Typical and atypical development. AB - The literature on visuospatial processing describes two distinct pathways within the brain: a dorsal route extending from the visual cortex into the parietal lobes that is critical for spatial processing and a ventral route extending from the visual cortex into the temporal lobes that is critical for form perception. These visual streams appear to differ in their developmental trajectories and their vulnerabilities to diverse neurodevelopmental conditions. The present work aims to investigate development and vulnerability in two aspects of dorsal and ventral visual-stream function, namely attention to location and attention to identity. In Study 1, we compare typically-developing (TD) youth aged 9 to 16 years with young adults aged 18 to 22 years on computerized location and identity tasks. In Study 2, we compare children and adolescents who have congenital hypothyroidism (CH), a pediatric endocrine disorder, with age-matched TD controls on the same tasks. The results from Study 1 show that the youths were less accurate than the adults at judging identity, whereas both groups were equally accurate at judging location. The results from Study 2 show that the youths with CH were slower but not less accurate than the TD youths in making both identity and location judgments. The results are interpreted as signifying later development of ventral (identity) stream functions compared to dorsal (location) but equal vulnerability of both functions in CH. PMID- 27279012 TI - Placental vascularization and apoptosis in Type-1 and gestational DM. AB - OBJECTIVE: The objective of this study is to analyze the alteration in vascularization and apoptosis in the placentas of patients with Type 1 or gestational diabetes mellitus. METHODS: Placental samples drawn from normal (n = 6), GDM (n = 6), and Type 1 DM (n = 6) pregnancies were rinsed in PBS and fixed in 4% paraformaldehyde. The obtained sections were examined by both light and electron microscopy. Subsequently, immunohistochemical staining was performed to evaluate apoptosis and vascularization with caspase-9 and VEGF antibodies. RESULTS: Capillary structures in various sizes, both in free and in stem villi, were observed to be denser in the GDM group than in the control and Type-1 DM groups, utilizing electron microscopy. Similarly, when compared with Type-1 DM and controls, a decreased amount of microvilli with more irregularity and blunting on the villus surface was detected. GDM group showed increased immunoreactivity in capillaries of stem villi, free villi, and endothelial cells when compared with Type-1 DM and control groups. Regarding the immunohistochemical staining with VEGF, Type-1 DM, and GDM groups showed stronger immunoreactivity than the control group, especially in syncytiotrophoblastic cell nuclei and stromal cell nuclei. However, there was no significant difference between Type-1 DM and GDM groups. CONCLUSION: Type-1 DM and GDM placentas showed increased villous stromal capillarization, increased immunoreactivity with VEGF and caspase-9, and increased syncytial nodes, which may develop secondary to placental hypoxia-ischemia. However, more participants are needed to confirm these conclusions. PMID- 27279013 TI - Accuracy of currently available neonatal respiratory function monitors for neonatal resuscitation. AB - This study aimed to test the accuracy in volume measurements of three available respiratory function monitors (RFMs) for neonatal resuscitation and the effect of changing gas conditions. The Florian, New Life Box Neo-RSD (NLB Neo-RSD) and NICO RFM were tested on accuracy with volumes of 10 and 20 mL and on changes in volume measurements under changing gas conditions (oxygen level 21-100 % and from cold dry air (24 +/- 2 degrees C) to heated humidified air (37 degrees C). Volume differences >10 % were considered clinically relevant. We found that the mean (SD) volume difference was clinically acceptable for all devices (10, 20 mL): Florian (+8.4 (1.2)%, +8.4 (0.5)%); NLB Neo-RSD (+5.8 (1.1)%, +4.3 (1.4)%); and NICO (-8.2 (0.9)%, -8.7 (0.8)%). Changing from cold dry to heated humidified air increased the volume difference using the Florian (cold dry air, heated humidified air (+5.2 (1.2)%, +12.2 (0.9)%) but not NLB Neo-RSD (+2.0(1.6)%, +3.4(2.8)%) and NICO (-2.3 % (0.8), +0.1 (0.6)%). Similarly, when using heated humidified air, increasing oxygen enlarged increased the volume difference using the Florian (oxygen 21 %, 100 %: +12.2(1.0)%, +19.8(1.1)%), but not NLB Neo-RSD (+0.2(1.9)%, +1.1(2.8)%) and NICO (-5.6(0.9)%, -3.7(0.9)%). Clinically relevant changes occurred when changing both gas conditions (Florian +25.7(1.7)%; NLB Neo RSD +3.8(2.4)%; NICO -5.7(1.4)%). CONCLUSION: The available RFMs demonstrated clinically acceptable deviations in volume measurements, except for the Florian when changing gas conditions. WHAT IS KNOWN: *Respiratory function monitors (RFMs) are increasingly used for volume measurements during respiratory support of infants at birth. *During respiratory support at birth, gas conditions can change quickly, which can influence the volume measurements. What is new: *The available RFMs have clinically acceptable deviations when measuring the accuracy of volume measurements. *The RFM using a hot wire anemometer demonstrated clinically relevant deviations in volume measurements when changing the gas conditions. These deviations have to be taken into account when interpreting the volumes directly at birth. PMID- 27279011 TI - Challenges in the diagnosis and management of acromegaly: a focus on comorbidities. AB - INTRODUCTION: Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. METHODS: We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. FINDINGS AND CONCLUSIONS: Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management. PMID- 27279014 TI - Congenital diaphragmatic hernia-influence of fetoscopic tracheal occlusion on outcomes and predictors of survival. AB - The morbidity of infants with congenital diaphragmatic hernia (CDH) who had undergone foetal endoscopic tracheal occlusion (FETO) to those who had not was compared and predictors of survival regardless of antenatal intervention were identified. FETO was undertaken on the basis of the lung to head ratio or the position of the liver. A retrospective review of the records of 78 CDH infants was undertaken to determine the lung-head ratio (LHR) at referral and prior to birth, maximum oxygen saturation in the labour suite and neonatal outcomes. The 43 FETO infants were born earlier (mean 34 versus 38 weeks) (p < 0.001). They had a lower mean LHR at referral (0.65 versus 1.24) (p < 0.001) but not prior to birth and did not have a higher mortality than the 35 non-FETO infants. The FETO infants required significantly longer durations of ventilation (median: 15 versus 6 days) and supplementary oxygen (28 versus 8 days) and hospital stay (29 versus 16 days). Overall, the best predictor of survival was the OI in the first 24 h. CONCLUSION: The FETO group had increased morbidity, but not mortality. The lowest oxygenation index in the first 24 h was the best predictor of survival regardless of antenatal intervention. WHAT IS KNOWN: * Randomised controlled trials have demonstrated that foetal endotracheal occlusion (FETO) in high risk infants with congenital diaphragmatic hernia is associated with a higher survival rate. * Mortality is greater in foetuses who underwent FETO and delivered prior to 35 weeks of gestation. What is New: * Infants who had undergone FETO compared to those who had not had significantly longer durations of mechanical ventilation, supplementary oxygen and hospital stay. * Regardless of antenatal intervention, the lowest oxygenation index in the first 24 h was the best predictor of survival. PMID- 27279015 TI - Morphometric and cytomorphologic characterization of EGFR-mutated cancer cells comparison between cultured lung cancer cell lines and lung adenocarcinoma clinical samples. AB - BACKGROUND: Recently molecular targeting therapies such as inhibition of enzyme activities associated with gene mutations responsible for lung carcinogenesis have been demonstrating promising outcomes, increasing the importance of gene analysis using clinical samples. Cytomorphologic findings with predictive value toward specific gene mutation such as EGFR mutation could be a useful tool to select appropriate gene analyses using limited clinical samples. METHODS: Morphometrical and cytomorphological evaluations were performed in 7 cultured lung cancer cell lines and 51 lung adenocarcinoma clinical samples to identify specific cytomorphologic characterization of EGFR-mutated cancer cells compared to the wild type. RESULTS: Morphometry demonstrated that the EGFR mutated cell lines had significantly smaller nuclear area and perimeter and more circular nuclei compared to the wild type. In contrast, EGFR-mutated clinical samples had significantly greater nuclear area and perimeter compared to the wild type EGFR samples. There were no clear differences in cytomorphologic parameters assessing nuclear atypicality between EGFR mutated cells and wild type EGFR cells in either cultured cell lines or clinical samples. CONCLUSION: Although our study suggested that EGFR mutation may have specific effects on nuclear morphology, no consistent characteristics of EGFR-mutated cells were identified in the clinical samples, probably due to various factors such as different pathologic stages and various incidences of lepidic growth. Further assessment of morphological characterization of EGFR-mutated cells in lung adenocarcinoma is warranted, increasing the number of samples and considering the effects of polyploidy, other gene mutations, pathology stage and tumor subtypes such as lepidic growth. Diagn. Cytopathol. 2016;44:717-724. (c) 2016 Wiley Periodicals, Inc. PMID- 27279018 TI - Manganese-catalyzed regiospecific sp(3) C-S bond formation through C-C bond cleavage of cyclobutanols. AB - A manganese-catalyzed regioselective sp(3) C-S bond formation through C-C bond cleavage of cyclobutanols is described. A variety of primary and secondary alkyl thioethers are efficiently prepared under mild reaction conditions. The mechanistic pathways involving radical-mediated tandem C-C bond cleavage and C-S bond formation are proposed. PMID- 27279016 TI - Overexpression of HSPA1A enhances the osteogenic differentiation of bone marrow mesenchymal stem cells via activation of the Wnt/beta-catenin signaling pathway. AB - HSPA1A, which encodes cognate heat shock protein 70, plays important roles in various cellular metabolic pathways. To investigate its effects on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its expression level was compared between undifferentiated and differentiated BMSCs. Rat HSPA1A overexpression in BMSCs increased osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Moreover, it upregulated beta-catenin and downregulated DKK1 and SOST. The enhanced osteogenesis due to HSPA1A overexpression was partly rescued by a Wnt/beta-catenin inhibitor. Additionally, using a rat tibial fracture model, a sheet of HSPA1A-overexpressing BMSCs improved bone fracture healing, as determined by imaging and histological analysis. Taken together, these findings suggest that HSPA1A overexpression enhances osteogenic differentiation of BMSCs, partly through Wnt/beta-catenin. PMID- 27279017 TI - Roscovitine ameliorates endotoxin-induced uveitis through neutrophil apoptosis. AB - Neutrophils have been recognized as critical response cells during the pathogenesis of endotoxin-induced uveitis (EIU). Apoptosis of neutrophils induced by roscovitine has previously been demonstrated to ameliorate inflammation in several in vivo models. The present study aimed to assess whether roscovitine ameliorates EIU. EIU was induced in female C57BL/6 mice by a single intravitreal injection of lipopolysaccharide (LPS; 250 ng). The mice were divided into three groups as follows: LPS alone, LPS plus vehicle, LPS plus roscovitine (50 mg/kg). The mice were euthanized 12, 24, 48 and 72 h after LPS-induced uveitis. Accumulation of inflammatory cells in the vitreous body was confirmed by immunohistochemistry, and quantified following hematoxylin and eosin staining. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was performed to detect of apoptotic cells. The mRNA levels of inflammatory cytokines were analyzed by reverse transcription-quantitative polymerase chain reaction and the changes in protein levels were analyzed by western blotting. Inflammatory cells accumulated in the vitreous near the optic nerve head and the quantity peaked at 24 h after LPS injection. Immunohistochemistry revealed that the majority of the inflammatory cells were neutrophils. The number of infiltrating cells was similar in the LPS and LPS plus vehicle groups, while there were significantly less in the roscovitine group at 24 h. Apoptosis of neutrophils was observed between 12 and 48 h after roscovitine injection, while no apoptosis was observed in the other groups. The mRNA expression levels of GMCSF, CINC-1 and ICAM-1 peaked at 12 h after LPS injection, and decreased to normal levels at 72 h. This trend in mRNA expression was similar in the LPS and LPS plus vehicle groups; however, the expression levels decreased more quickly in the roscovitine group at 24 and 48 h. Following roscovitine administration, upregulated cleaved caspase 3 expression levels and downregulated Mcl-1 expression levels were observed. In conclusion, roscovitine ameliorates EIU by effecting neutrophil apoptosis. Timely apoptosis of neutrophils may be an effective process to promote the amelioration of EIU. PMID- 27279019 TI - Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors. AB - To elucidate the immunological mechanisms critical for tumor progression, we bred novel mouse strains, different in the NKC and H-2D domains. We used inbreeding to generate hybrids of Balb/c and C57BL/6 of stable H-2Db+d-NK1.1neg and H-2Db d+NK1.1high phenotypes. We analyzed the growth of three established MHC class I deficient tumor cell lines: TC-1/A9 tumor (HPV-associated) and B16F10 melanoma, both syngeneic to C57BL/6, and the MCB8 (3-methycholanthrene-induced tumor) syngeneic to Balb/c. Furthermore, we induced colorectal carcinoma by azoxymethane DSS treatment to test the susceptibility to chemically-induced primary cancer. We found that the novel strains spontaneously regressed the tumor transplants syngeneic to both Balb/c (MCB8) and C57BL/6 (B16F10 and TC-1/A9) mice. The H2 Db+d-NK1.1neg, but not the H2-Db-d+NK1.1high strain was also highly resistant to chemically-induced colorectal cancer in comparison to the parental mice. The immune changes during TC-1/A9 cancer development involved an increase of the NK cell distribution in the peripheral blood and spleen along with higher expression of NKG2D activation antigen; this was in correlation with the time-dependent rise of cytotoxic activity in comparison to C57BL/6 mice. The TC-1/A9 cancer regression was accompanied by higher proportion of B cells in the spleen and B220+/CD86+ activated antigen-presenting B cells distributed in the lymphoid organs, as well as in the periphery. The changes in the T-cell population were represented mainly by the prevalence of T helper cells reflected by grown CD4/CD8 ratio, most prominent in the b+d-NK1.1neg strain. The results of the present study imply usefulness of the two novel mouse strains as an experimental model for further studies of tumor resistance mechanisms. PMID- 27279020 TI - Self-Heating and Failure in Scalable Graphene Devices. AB - Self-heating induced failure of graphene devices synthesized from both chemical vapor deposition (CVD) and epitaxial means is compared using a combination of infrared thermography and Raman imaging. Despite a larger thermal resistance, CVD devices dissipate >3x the amount of power before failure than their epitaxial counterparts. The discrepancy arises due to morphological irregularities implicit to the graphene synthesis method that induce localized heating. Morphology, rather than thermal resistance, therefore dictates power handling limits in graphene devices. PMID- 27279021 TI - Retraction notice to "Antinociceptive effects of endomorphin-2: Suppression of substance P release in the inflammatory pain model rat". PMID- 27279022 TI - Glyco-gold nanoparticle shapes enhance carbohydrate-protein interactions in mammalian cells. AB - Advances in shape-dependent nanoparticle (NP) research have prompted a close scrutiny of the behaviour of nanostructures in vitro and in vivo. Data pertaining to cellular uptake and site specific sequestration of different shapes of NPs will undoubtedly assist researchers to design better nano-probes for therapeutic and imaging purposes. Herein, we investigated the shape dependent uptake of glyco gold nanoparticles (G-AuNPs) in different cancer cell lines. Specifically, we have compared the behaviour of spherical, rod and star AuNPs with mannose and galactose conjugations. In vitro experiments showed that the rod-AuNPs exhibited the highest uptake over that of the star and spherical counterparts. Further, an investigation of the mechanism of the uptake clearly demonstrated clathrin mediated endocytosis of the specific G-AuNPs. These results reveal the benefits of different G-AuNP shapes in carbohydrate-mediated interactions. PMID- 27279023 TI - Prognostic risk model development and prospective validation among patients with cervical cancer stage IB2 to IIB submitted to neoadjuvant chemotherapy. AB - This study was designed to develop a risk model for disease recurrence among cervical cancer patients who underwent neoadjuvant chemotherapy and radical surgery. Data for 853 patients were obtained from a retrospective study and used to train the model, and then data for 447 patients from a prospective cohort study were employed to validate the model. The Cox regression model was used for calculating the coefficients of the risk factors. According to risk scores, patients were classified into high-, intermediate-, and low-risk groups. There were 49 (49/144, 34%) recurrences observed in the high-risk group (with a risk score >= 2.65), compared with 3 (3/142, 2%) recurrences in the low-risk group (with a risk score < 0.90). Disease-free survival (DFS) was significantly different (log-rank p < 0.001) among the three risk groups; the risk model also revealed a significant increase in the accuracy of predicting 5-year DFS with the area under the ROC curve (AUC = 0.754 for risk model vs 0.679 for FIGO stage system); the risk model was also validated with data from the prospective study (log-rank p < 0.001, AUC = 0.766). Both high-risk and intermediate-risk patients can be more effectively identified by this risk model. PMID- 27279024 TI - Immunosuppression in the elderly renal allograft recipient: a systematic review. AB - BACKGROUND: The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. METHODS: We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. RESULTS: Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus avoidance using mycophenolate mofetil (MMF). Observational cohort studies looked at different antibody induction strategies, calcineurin-inhibitors based maintenance immunosuppression, calcineurin-inhibitor-free sirolimus-based therapy and use of MMF versus azathioprine. Treatment with interleukin-2 receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account the morbid consequences of acute rejection in the elderly, observational studies support antibody induction with depletive antibodies, calcineurin-inhibitor, MMF and steroids; calcineurin inhibitor-minimization is not recommended. CONCLUSIONS: There is very limited evidence for the benefits and harms of different immunosuppression strategies in the elderly. Most of the published literature are observational studies, and randomized controlled trials are urgently needed. PMID- 27279025 TI - Adult vaccination against tetanus and diphtheria: the European perspective. AB - Besides immunizations against influenza, Streptococcus pneumoniae and herpes zoster, which are recommended specifically for elderly people, regular booster vaccinations against tetanus, diphtheria and in some cases pertussis and polio are recommended in many European countries for adults, including elderly people. Vaccination recommendations for adults differ greatly between individual countries and coverage data is scarce. Tetanus-specific antibody concentrations are generally higher than diphtheria-specific antibodies, and a substantial proportion of adults, and particularly of elderly people, do not have protective antibody concentrations against diphtheria. Antibody levels increase upon booster vaccination in all age groups, but diphtheria-specific antibody concentrations remain below protective levels in some older individuals, even immediately after vaccination and long-term protection is frequently not achieved. Future vaccination strategies should therefore include regular and well-documented booster shots, e.g. against tetanus and diphtheria, throughout life. PMID- 27279026 TI - Efficient production of acetoin in Saccharomyces cerevisiae by disruption of 2,3 butanediol dehydrogenase and expression of NADH oxidase. AB - Acetoin is widely used in food and cosmetic industry as taste and fragrance enhancer. For acetoin production in this study, Saccharomyces cerevisiae JHY605 was used as a host strain, where the production of ethanol and glycerol was largely eliminated by deleting five alcohol dehydrogenase genes (ADH1, ADH2, ADH3, ADH4, and ADH5) and two glycerol 3-phosphate dehydrogenase genes (GPD1 and GPD2). To improve acetoin production, acetoin biosynthetic genes from Bacillus subtilis encoding alpha-acetolactate synthase (AlsS) and alpha-acetolactate decarboxylase (AlsD) were overexpressed, and BDH1 encoding butanediol dehydrogenase, which converts acetoin to 2,3-butanediol, was deleted. Furthermore, by NAD(+) regeneration through overexpression of water-forming NADH oxidase (NoxE) from Lactococcus lactis, the cofactor imbalance generated during the acetoin production from glucose was successfully relieved. As a result, in fed-batch fermentation, the engineered strain JHY617-SDN produced 100.1 g/L acetoin with a yield of 0.44 g/g glucose. PMID- 27279027 TI - Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings. AB - BACKGROUND: In single gene disorders, patients with the same genotype may have variations in severity. One of the main factors affecting disease severity is modifier genes. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by degeneration of alpha motor neurons. Plastin 3 (PLS3) is a phenotypic modifier of SMA, and neuritin 1 (NRN1) has also been suggested as a possible modifier gene. The aim of the present study was therefore to analyze PLS3 and NRN1 expression in SMA siblings in four families. METHODS: The study group consisted of four SMA families with seven with discordant phenotype and two affected siblings. Total RNA was isolated from whole blood. PLS3 and NRN1 expression was analyzed on quantitative real-time polymerase chain reaction. RESULTS: In family 1 only NRN1 expression was increased in the mildly affected sister. In family 2 only PLS3 had a modifier effect. Family 3, which had type III siblings with identical clinical phenotypes, had similar PLS3 expression between the siblings but no NRN1 expression. In family 4, neither PLS3 nor NRN1 had any correlation with severity. CONCLUSION: On analysis of the expression of NRN1 in SMA patients for the first time, NRN1 could be a potential modifier gene. PLS3 expression does not always modify SMA phenotype. In patients with no modifier effect of known genes, genome sequencing and transcriptome analysis are promising for the identification of novel modifiers and understanding of SMA pathophysiology. PMID- 27279028 TI - Developmental origin of the clavicle, and its implications for the evolution of the neck and the paired appendages in vertebrates. AB - In fish, the pectoral appendage is adjacent to the head, but during vertebrate evolution a long neck region emerged via caudal relocation of the pectoral appendage. The pectoral appendage is comprised of endochondral portions, such as the humerus and the scapula, and a dermal portion, such as the clavicle, that contributes to the shoulder girdle. In the search for clues to the mechanism of the caudal relocation of the pectoral appendage, the cell lineage of the rostral lateral plate mesoderm was analyzed in chickens. It was found that, despite the long neck region in chickens, the origin of the clavicle attached to the head mesoderm ranged between 1 and 14 somite levels. Because the pectoral limb bud and the endochondral pectoral appendage developed on 15-20 and 15-24 somite levels, respectively, the clavicle-forming region corresponds to the embryonic neck, which suggests that the relocation would have been executed by the expansion of the source of the clavicle. The rostral portion of the clavicle-forming region overlaps the source of the cucullaris muscle, embraces the pharyngeal arches caudally, and can be experimentally replaced with the head mesoderm to form the cucullaris muscle, which implies that the mesodermal portion could have been the head mesoderm and that the clavicle would have developed at the head/trunk boundary. The link between the head mesoderm and the presumptive clavicle appears to have been the developmental constraint needed to create the evolutionarily conserved musculoskeletal connectivities characterizing the gnathostome neck. In this sense, the dermal girdle of the ganathostomes would represent the wall of the branchial chamber into which the endochondral pectoral appendage appears to have attached since its appearance in evolution. PMID- 27279029 TI - Homeostatic maintenance via degradation and repair of elastic fibers under tension. AB - Cellular maintenance of the extracellular matrix requires an effective regulation that balances enzymatic degradation with the repair of collagen fibrils and fibers. Here, we investigate the long-term maintenance of elastic fibers under tension combined with diffusion of general degradative and regenerative particles associated with digestion and repair processes. Computational results show that homeostatic fiber stiffness can be achieved by assuming that cells periodically probe fiber stiffness to adjust the production and release of degradative and regenerative particles. However, this mechanism is unable to maintain a homogeneous fiber. To account for axial homogeneity, we introduce a robust control mechanism that is locally governed by how the binding affinity of particles is modulated by mechanical forces applied to the ends of the fiber. This model predicts diameter variations along the fiber that are in agreement with the axial distribution of collagen fibril diameters obtained from scanning electron microscopic images of normal rat thoracic aorta. The model predictions match the experiments only when the applied force on the fiber is in the range where the variance of local stiffness along the fiber takes a minimum value. Our model thus predicts that the biophysical properties of the fibers play an important role in the long-term regulatory maintenance of these fibers. PMID- 27279041 TI - The Youth Daily Life Before Fulfilling Socio-educational Measures of Deprivation of Liberty in Brazil: Ordinary Experiences That Are Tangent to the Inclusion in Drug Trafficking. AB - The aim of this paper is to demonstrate some understanding of the daily lives of young people facing socio-educational measures of incarceration, especially regarding the predisposing factors that may explain their involvement in criminal occupations and activities (Although the socio-educational measures applicable to adolescents configures as a response to committing of an offence, it has a mostly educational and not punitive character.). This is an exploratory study with a qualitative approach. The data collection instrument used was semi-structured interviews with 22 young men aged between 12 and 17 years, on condition of deprivation of freedom in four youth centres in Belo Horizonte, Minas Gerais, Brazil. The results showed that these adolescents had a way of life associated with a scarcity of resources owned by households (including little control over them, despite the efforts of their mothers); low adherence to school; limited institutional access to activities in their free time; exposure to predisposing factors to crime, such as early contact with crime through neighbourhood and family relationships; and profiting from crime. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27279040 TI - Nitidine chloride suppresses epithelial-to-mesenchymal transition in osteosarcoma cell migration and invasion through Akt/GSK-3beta/Snail signaling pathway. AB - Metastasis is the main cause of death in osteosarcoma. Targeting the process of metastasis is a main strategy for osteosarcoma therapy. As a traditional Chinese medicine, Zanthoxylum nitidum (Roxb) has been applied to treat various diseases, including cancer. However, no evidence has been shown on the anti-metastasis effect of nitidine chloride (NC) that was extracted from Zanthoxylum nitidum (Roxb) on osteosarcoma cells, or its underling mechanisms. In the present study, we aimed to demonstrate the role of NC on the migration and invasion of osteosarcoma cells. Viability and proliferation of osteosarcoma cells were examined by MTT assay. Then, by appling scratch wound healing assay and Transwell assays, we evaluated migratory and invasive ability of the cells, respectively. Moreover, the expression of epithelial-to-mesenchymal transition (EMT) markers were determined after treatment with NC. Furthermore, the expression of Akt, GSK 3beta and Snail were detected by western blot analysis. In addition, the GSK 3beta activity was examined by GSK-3beta kinase assay. Finally, an inhibitor of GSK-3beta, lithium chloride (LiCl) was applied to testify the effect of NC on the expression of EMT markers and Snail. We found that the proliferative, migratory and invasive ability of the U2OS osteosarcoma cells were all suppressed when treated with NC. NC increased the expression of E-cadherin and decreased the expression of N-cadherin, vimentin and fibronectin in a dose-dependent manner. NC also exerted its ability to suppress the phosphorylation of Akt and GSK-3beta so as to activate GSK-3beta. Then, by using an GSK-3beta inhibitor, LiCl, we revealed the effect of GSK-3beta in the expression of EMT markers. The expression of Snail was inhibited when treated with NC and LiCl also reversed the NC inhibited Snail expression. Taken together, these results revealed that NC suppressed EMT and decreased the invasive ability of osteosarcoma cells via the Akt/GSK-3beta/snail signaling pathway. PMID- 27279039 TI - Global Tn-seq analysis of carbohydrate utilization and vertebrate infectivity of Borrelia burgdorferi. AB - Borrelia burgdorferi maintains a complex life cycle between tick and vertebrate hosts. Although some genes have been identified as contributing to bacterial adaptation in the different hosts, the list is incomplete. In this manuscript, we report the first use of transposon mutagenesis combined with high-throughput sequencing (Tn-seq) in B. burgdorferi. We utilize the technique to investigate mechanisms of carbohydrate utilization in B. burgdorferi and the role of carbohydrate metabolism during mouse infection. We performed genetic fitness analyses to identify genes encoding factors contributing to growth on glucose, maltose, mannose, trehalose and N-acetyl-glucosamine. We obtained insight into the potential functions of proteins predicted to be involved in carbohydrate utilization and identified additional factors previously unrecognized as contributing to the metabolism of the tested carbohydrates. Strong phenotypes were observed for the putative carbohydrate phosphotransferase transporters BB0408 and BBB29 as well as the response regulator Rrp1. We further validated Tn seq for use in mouse studies and were able to correctly identify known infectivity factors as well as additional transporters and genes on lp54 that may contribute to optimal mouse infection. As such, this study establishes Tn-seq as a powerful method for both in vitro and in vivo studies of B. burgdorferi. PMID- 27279042 TI - Mechanisms of Cytotoxic Lymphocyte-Mediated Apoptosis and Relationship with the Tumor Suppressor p53. AB - Cytotoxic T lymphocytes and natural killer cells are key effector cells in the immune response against intracellular infection and transformed cells. These killer cells induce multiple programs of cell death to achieve their function of eliminating their targets. In this review, we summarize our current understanding of the signaling pathways involved in target cells apoptosis triggered by the cytotoxic effector cells. We also discuss the role of an important player in the field of apoptosis, the well-known p53 tumor suppressor, in the modulation of cytotoxic lymphocyte-mediated cell death. PMID- 27279044 TI - Identification of Antigen-Specific B-Cell Receptor Sequences from the Total B Cell Repertoire. AB - Advances in next-generation sequencing now allow characterization of the global B cell receptor (BCR) heavy-chain repertoire at a level that reflects its huge diversity. This technology has provided great insight into the structure of the BCR repertoire and how it responds to specific antigen stimuli. There are numerous potential clinical and research applications of BCR repertoire sequencing, but a major hurdle in the realization of these applications is the identification of the antigen-specific sequences of interest from within the total repertoire. To deconvolute the antigen-specific sequences from total repertoire, either a source of antigen-enriched sequence data is required with which to annotate the total repertoire, or de novo annotation methods must be used based on preconceptions of the features of antigen-specific sequences and their behavior following antigen-specific immune stimulation. We present a review of how these different methods can be applied to identify antigen-specific BCR sequences from the total BCR repertoire. PMID- 27279043 TI - Interleukin-33 and its Receptor in Pulmonary Inflammatory Diseases. AB - Interleukin-33 (IL-33) is a member of the IL-1 cytokine family. It modulates immune responses and biological functions through binding to its membrane receptor, ST2L. ST2L is a member of the Toll-like/IL-1 (TIR)-receptor superfamily, and its isoform, soluble ST2 (sST2), functions as an inhibitor of the IL-33/ST2L pathway. Levels of IL-33 and sST2 in serum and bronchoalveolar lavage fluid (BAL) are known biomarkers for a variety of disorders such as heart failure, non-small-cell lung cancer, and pulmonary inflammatory diseases. IL-33 also exists in the nuclei, and nuclear IL-33 seems to regulate cytokine gene expression. In this review, we focus on the role of IL-33/ST2 in the pathogenesis of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung injury. PMID- 27279045 TI - Regulatory T-Cell Therapy in Transplantation and Severe Autoimmunity. AB - Current approaches to prevent or treat transplant rejection, graft-versus-host disease and severe autoimmunity rely on non-specific immunosuppressive drugs. Ongoing efforts aimed at harnessing regulatory T (Treg) cells hold promise for revolutionizing the current therapeutic options, reducing if not abandoning immune suppression in favor of immune tolerance. This paradigm shift carries the potential of dramatically enhancing efficacy, persistency, and specificity while reducing side effects. Here, we review the various strategies devised to manipulate Treg cells in vitro and in vivo, the clinical progress achieved to date, and critical issues that still need to be addressed. PMID- 27279048 TI - Erratum to: Impact of energy loss index on left ventricular mass regression after aortic valve replacement. PMID- 27279047 TI - Sirtuin 1 promotes the proliferation of C2C12 myoblast cells via the myostatin signaling pathway. AB - Accumulating evidence suggests that Sirtuin (Sirt)1 serves a significant role in proliferation and differentiation of myoblast cells; however the signaling mechanisms involved remain to be established. Myostatin (MSTN), a member of transforming growth factor-beta family, is an vital regulator of myoblast, fibroblast growth and differentiation. To determine if MSTN is involved in the regulation of myoblast cell proliferation by Sirt1, the present study administrated the Sirt1 activator resveratrol, inhibitor nicotinamide (NAM) and MSTN inhibitor SB431542 to C2C12 myoblast cells. It was demonstrated that the Sirt1 activator, resveratrol, repressed, whereas the Sirt1 inhibitor, NAM, enhanced C2C12 myoblast cells proliferation in a Sirt1-dependent manner. SB431542 promoted the proliferation of C2C12 myoblast cells and reversed the inhibition effect of NAM on C2C12 myoblast cell proliferation. Additionally, resveratrol upregulated the mRNA expression of MyoD, but inhibited the expression of MSTN. Additionally, NAM significantly repressed the expression of MyoD and the phosphorylation of P107 (p-P107), but enhanced the expression of MSTN and the protein expression of P107. SB431542 significantly mitigated the effect of NAM on the expression of MyoD, P107 and p-P107. Taken together, these results indicated that Sirt1 promotes the proliferation of C2C12 myoblast cells via the MSTN signaling pathway. PMID- 27279049 TI - Echocardiographic assessment of anomalous origin of the left coronary artery from the pulmonary artery. AB - Transthoracic echocardiography of a 4-month-old boy with heart failure revealed poor left ventricular contractility with severe mitral regurgitation. Deformation analysis revealed significantly decreased circumferential strain in the anterior and anteroseptal segments. Furthermore, post-systolic shortening was evident in the anterior and lateral segments. The pulmonary arterial short-axis view showed that the left coronary artery originated from the pulmonary artery and color Doppler flow mapping showed retrograde flow in the left coronary artery. These findings were quite helpful for concluding the anomalous origin of the left coronary artery from the pulmonary artery. PMID- 27279046 TI - Opportunities for Translation from the Bench: Therapeutic Intervention of the JAK/STAT Pathway in Neuroinflammatory Diseases. AB - Pathogenic CD4+ T cells and myeloid cells play critical roles in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. These immune cells secrete aberrantly high levels of pro inflammatory cytokines that pathogenically bridge the innate and adaptive immune systems and damage neurons and oligodendrocytes. These cytokines include interleukin-2 (IL-2), IL-6, IL-12, IL-21, IL-23, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon-gamma (IFN-gamma). It is, therefore, not surprising that both the dysregulated expression of these cytokines and the subsequent activation of their downstream signaling cascades is a common feature in MS/EAE. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is utilized by numerous cytokines for signal transduction and is essential for the development and regulation of immune responses. Unbridled activation of the JAK/STAT pathway by pro-inflammatory cytokines has been demonstrated to be critically involved in the pathogenesis of MS/EAE. In this review, we discuss recent advancements in our understanding of the involvement of the JAK/STAT signaling pathway in the pathogenesis of MS/EAE, with a particular focus on therapeutic approaches to target the JAK/STAT pathway. PMID- 27279050 TI - Right ventricular thrombosis in two patients with pulmonary atresia with intact ventricular septum. AB - Thrombosis was detected in the right ventricle 7 days after a bidirectional Glenn operation in a 1-year-old boy with pulmonary atresia with intact ventricular septum (PAIVS) and immediately before pulmonary valvuloplasty in a 21-day-old boy with PAIVS. The risk of thrombosis and the blood clotting cascade should be assessed by blood tests, and surveillance echocardiography should be frequently applied in order to diagnose thrombosis early in such patients. PMID- 27279051 TI - Unicuspid aortic valve in a middle-aged man: a rare case report. AB - Unicuspid aortic valve is a rare congenital anomaly. Two forms of unicuspid aortic valve exist: acommisural and unicommisural forms, both with a predisposition to aortic dilatation. Most patients with this congenital abnormality will eventually require therapeutic intervention for resulting severe aortic stenosis during infancy or childhood. In adults, the most common treatment applied is aortic valvular replacement associated with replacement of the aortic root and ascending aorta. We describe a 43-year-old man admitted to our hospital complaining of chest pain with the diagnosis of acute coronary syndrome. Transthoracic and transesophageal echocardiography showed a unicommisural unicuspid aortic valve associated with an aneurysmally dilated ascending aorta. The patient underwent a Bentall operation and was discharged uneventfully. PMID- 27279052 TI - Beta-blocker stress echocardiography in an aortic stenosis patient with associated left ventricular outflow tract obstruction. AB - An 80-year-old man visited our hospital because of dyspnea on exertion from 6 months ago. Echo Doppler study showed severe calcification in the aortic valve with restricted movement and the sigmoid septum causing obstruction at the LV outflow tract (LVOT). Considering the aortic valve area (AVA) might have been inaccurately estimated, we carried out beta-blocker stress echocardiography. The transaortic pressure gradient and AVA were respectively calculated as 52 mmHg and 0.90 cm(2) before propranolol administration and as 64 mmHg and 0.86 cm(2) after propranolol administration. Thus, beta-blocker stress echocardiography may provide an accurate assessment of AS if the LVOT obstruction is concomitant. PMID- 27279053 TI - Perforation of the hypopharynx after transesophageal echocardiography. AB - A 65-year-old obese woman with an oversized neck and dysphagia underwent transesophageal echocardiography (TEE). The procedure was complicated by difficulty in insertion from the pharynx to esophagus, and her head and neck gradually swelled. Computed tomography (CT) revealed extensive emphysema from the neck to superior mediastinum, which suggested pharyngeal perforation. A nasogastric tube was inserted, and the patient received antibiotics to prevent secondary mediastinitis. CT performed 1 week later showed improvement of emphysema and no evidence of mediastinitis. Perforation along the orogastric pathway during TEE is a rare but life-threatening complication to which physicians performing TEE should pay attention. PMID- 27279054 TI - Early failure of quadricuspid aortic valve tricuspidization due to dehiscence of approximating coronary cusps. AB - A 48-year-old woman diagnosed with aortic regurgitation showing a quadricuspid aortic valve (QAV) underwent repair with tricuspidization. Two non-coronary cusps (NCC) with fenestrations were detected intraoperatively. Tricuspidization of QAV was performed by approximating the two NCCs via interrupted sutures. The aortic annulus was plicated by subcommissural annuloplasty. The residual aortic regurgitation was mild, with a vena contracta of 2.1 mm. On postoperative day 5, echocardiography demonstrated a new regurgitation from the middle of the neo-NCC, and increased central regurgitation. Intraoperative findings showed the dehiscence of approximating sutures of the neo-NCC. Mechanical valve replacement was performed uneventfully. PMID- 27279055 TI - Mid-systolic flow reversal in a patient with mid-ventricular obstructive hypertrophic cardiomyopathy. PMID- 27279056 TI - Massive thrombus in the left ventricle: a case report. PMID- 27279057 TI - 'Aortic valve prolapse' in rheumatic heart disease. PMID- 27279058 TI - [Non-communicable disease and their significance for dental medicine]. AB - Non-communicable diseases (NCDs), such as cardiovascular diseases, chronic respiratory diseases, cancers, and diabetes mellitus, are responsible for most deaths worldwide. In view of the rising prevalence and the long-term consequences of NCDs, their prevention is a public health priority. Dentistry plays an important role in this endeavor. Since oral and general diseases share common risk factors (e.g., poor oral hygiene, unhealthy diet, alcohol abuse, tobacco consumption, distress), preventive measures may target both oral diseases (e.g., dental caries, periodontal diseases, oral tumors) and medical NCDs. Consequently, dental medicine assumes an important medical and social role, which has been recognized by the World Health Organization and the General Assembly of the United Nations. To fulfill its mission successfully, consideration of the principles of evidence-based dentistry is a prerequisite. At the same time, the new development provides dentistry with the opportunity to critically reflect on its current and future orientation. PMID- 27279059 TI - Epigenetic regulation of KLK7 gene expression in pancreatic and cervical cancer cells. AB - Kallikrein-related peptidase 7 (KLK7) is a serine protease encoded within the kallikrein gene cluster located on human chromosome region 19q13.3-13.4. KLK7 is overexpressed in human pancreatic ductal adenocarcinomas (PDACs), but not in normal pancreas. Examination of KLK7 mRNA levels in pancreatic cancer cell lines revealed that it is readily detected in MIA PaCa-2 and PK-1 cells, but not in Panc-1 cells. Treatment of Panc-1 cells with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) significantly induced KLK7 mRNA expression. Similarly, KLK7 is highly expressed in cervical cancer cells, but its expression in the human cervical cancer cell line HeLa is only detected following TSA treatment. Promoter deletion analysis revealed that the proximal -238 promoter region, containing a putative Sp1-binding site, was sufficient for TSA activation of luciferase reporter activity, which was abrogated by the disruption of the Sp1 binding sequence. Consistent with the notion that TSA induced KLK7 expression via Sp1, co-expression of Sp1 with the KLK7-promoter/luciferase construct produced a significant increase in reporter activity. Chromatin immunoprecipitation (ChIP) analysis revealed enriched Sp1 occupancy on the KLK7 promoter following TSA treatment. Similarly, ChIP analysis showed the histone active mark, H3K4Me3, in the KLK7 promoter region was significantly increased after exposure to TSA. PMID- 27279060 TI - Common therapeutic strategies for prion and Alzheimer's diseases. AB - A number of unexpected pathophysiological connections linking different neurodegenerative diseases have emerged over the past decade. An example is provided by prion and Alzheimer's diseases. Despite being distinct pathologies, these disorders share several neurotoxic mechanisms, including accumulation of misfolded protein isoforms, stress of the protein synthesis machinery, and activation of a neurotoxic signaling mediated by the cellular prion protein. Here, in addition to reviewing these mechanisms, we will discuss the potential therapeutic interventions for prion and Alzheimer's diseases that are arising from the comprehension of their common neurodegenerative pathways. PMID- 27279061 TI - Novel quinolines carrying pyridine, thienopyridine, isoquinoline, thiazolidine, thiazole and thiophene moieties as potential anticancer agents. AB - As a part of ongoing studies in developing new anticancer agents, novel 1,2 dihydropyridine 4, thienopyridine 5, isoquinolines 6-20, acrylamide 21, thiazolidine 22, thiazoles 23-29 and thiophenes 33-35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2 dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2 dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27-45 MUmol L-1) compared to doxorubicin (IC50 47.9 MUmol L-1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3 dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7 carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl) 1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin. PMID- 27279062 TI - Piecewise function parameters as responses of the design of experiment in the development of a pulsatile release chronopharmaceutical system. AB - The aim of this work was to develop a pulsatile release system with metoprolol for chronotherapeutical use by coating swellable mini-tablets with Eudragit RS. To study the influence of the formulation factors (amount of coating polymer, plasticizer percentage in film coating and swelling agent percentage in mini tablets), a Box-Behnken design of experiment (DoE) was used. To evaluate the influence of the studied factors on the sigmoid shape of the dissolution profile, piecewise function parameters were used as the responses of DoE. The results show that higher concentrations of coating polymer and higher concentrations of plasticizer polymer led to a thicker and more elastic polymeric film, which led to a delay in drug release. Using the parameters of the piecewise function as DoE responses, an optimum formulation with a sigmoid shape dissolution profile and a 2.5-h lag time followed by rapid drug release were obtained. PMID- 27279063 TI - Study of the effect of formulation variables on the characteristics of combination tablets containing enalapril maleate and indapamide as active substances using experimental design. AB - To evaluate the influence of different variables on tablet formulations containing enalapril maleate and indapamide as active substances, two separate experimental designs were employed: one for evaluating powder properties and the other for tablet characteristics. Because of the low active pharmaceutical ingredient content, it was hypothesized that both powder and tablet properties could be determined only by the characteristics of excipients. In order to test this assumption, both experimental designs were done with placebo mixtures. The optimized formulation was then evaluated both with and without APIs. Results indicated that filler and lubricant percentage, along with compression force, were the most important variables during the formulation study. The optimized formulation showed similar characteristics in both cases for all responses, except for angle of repose and friability where only minor differences were observed. The combination of the applied approaches (using placebo composition and fractional experimental design) proved to be efficient, cost effective and time saving. PMID- 27279064 TI - The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process. AB - Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl beta-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-beta-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content). PMID- 27279065 TI - Synthesis of some benzimidazole derivatives endowed with 1,2,3-triazole as potential inhibitors of hepatitis C virus. AB - New derivatives of 2-thiobenzimidazole incorporating triazole moiety were synthesized, characterized and tested in vitro for antiviral activity against hepatitis C virus (HCV) and hepatitis B virus (HBV). Their cytotoxicity was determined by the reduction in the number of viable cell. All of the synthesized compounds are inactive against HBV and some showed activity against HCV. In particular, two compounds showed significant activity, 2-{4-[(1 benzoylbenzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitro-phenyl) acetamide (13) and 2-(4-{[1-(p-chlorobenzoyl)-benzimidazol-2-ylthio)methyl]-1H 1,2,3-triazol-1-yl}-N-(p-nitrophenyl)-acetamide (17). The results give an insight into the importance of the substituent at position 2 of benzimidazole for the inhibition of HCV. PMID- 27279066 TI - Evaluation of the topical spray containing Centella asiatica extract and its efficacy on excision wounds in rats. AB - Centella asiatica was extracted by methanol. The assay content of triterpenes in the extract was 0.12 % asiatic acid, 0.54 % madecassic acid, 0.25 % asiaticoside and 1.02 % madecassoside. The extract was complexed with hydroxypropyl-beta cyclodextrin (HP-beta-CD) and formulated with Eudragit E100, glycerol, PEG 400, copovidone, ethanol and purified water. A clear yellowish solution (F1-F8) was obtained. The formulations had a pH of 5.5-6.0 with viscosity in the range of 20 60 mPa s, surface tension 20.3-24.6 mN m-1 and contact angle less than 20 degrees . The amount of PEG 400 and copovidone affected the film and spreadability. The content of triterpenes in the spray formulation was close to 100 % compared to triterpenes in the extract. The skin irritation study indicated that the formulation was non-irritating in a rat model. An in vivo excision wound healing model showed that wound excision was completely healed after 14 days. PMID- 27279067 TI - Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain. AB - A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach. PMID- 27279068 TI - Coated pellets with delayed-release glucose for prevention of hypoglycemic episodes. AB - Patients tend to prevent hypoglycemia by excessive saccharide intake leading to poorer glycemic control with potentially fatal consequences. This problem could be resolved by means of pellets with glucose release delayed by 120-360 min as a compensation of the antidiabetic drug peak effect. No glucose is released before; hence there is no risk of hyperglycemia and secondary complications. The pellets contain glucose in combination with an osmotically active ingredient and are coated with an ethylcellulose dispersion, which forms an insoluble semipermeable membrane and ensures delayed release. The release of glucose was assessed using dissolution and high-performance liquid chromatography. Dissolution profiles indicated the possibility of achieving the requested lag time using a combination of adequate compositions and coating concentrations. Lag times of 60, 240 and 360 min were achieved. The sample containing carboxymethyl starch was found to be most suitable for the intent of this work. PMID- 27279069 TI - Release of selected amino acids from zinc carriers. AB - The paper deals with the results of an investigation of the release of selected amino acids (histidine, tryptophan, tyrosine) from model suspensions prepared by co-precipitation with zinc chloride. It has been proven that the influence of the Zn(II)/amino acid molar ratio on dissolution profiles of the tested amino acids and dissolution half-life (t1/2) of histidine or tryptophan is significant. The amount of amino acid in the dispersed phase (supporting dose) is a determinant of the amino acid release profile. There is a minimal supporting dose (30.0 MUmol of histidine or 17.4 MUmol of tryptophan) that provides release of similar amounts of amino acid (4.1-4.6 MUmol of histidine or 8.7-9.9 MUmol of tryptophan) after the same time intervals. The tyrosine release profiles follow first order kinetics since the supporting dose (0.9-11.2 MUmol) is limited by the tyrosine low solubility in water. PMID- 27279070 TI - Pharmacokinetic comparisons of S-oxiracetam and R-oxiracetam in beagle dogs. AB - A pharmacokinetic comparison and conformational stability study of S-oxiracetam (S-ORT) and R-oxiracetam (R-ORT) in beagle dogs was used to investigate the possible mechanism of different effects of two oxiracetam enantiomers through a random crossover design. After drug administration to beagle dogs, blood samples were collected at different time points for pharmacokinetic analysis using the UPLC-ESI-MS/MS method. Parts of plasma samples were used for conformation transformation studies using a normal phase high performance liquid chromatographic (NP HPLC) method. The study showed that oxiracetam enantiomers maintained their original conformation when administered orally to beagle dogs. Concentrations of S-ORT were significantly higher than R-ORT 1.5 and 2 h after administration; the AUC0-infinity of S-ORT after oral administration tended to be higher than that of R-ORT, which showed that the different effects between S-ORT and R-ORT may be partly associated with their distinctive absorption at least. PMID- 27279071 TI - Optimized genotyping method for identification of bacterial contaminants in pharmaceutical industry. AB - Microbiological control is of crucial importance in the pharmaceutical industry regarding the possible bacterial contamination of the environment, water, raw materials and finished products. Molecular identification of bacterial contaminants based on DNA sequencing of the hypervariable 16SrRNA gene has been introduced recently. The aim of this study is to investigate the suitability of gene sequencing using our selection of PCR primers and conditions for rapid and accurate bacterial identification in pharmaceutical industry quality control. DNA was extracted from overnight incubated colonies from 10 bacterial ATCC strains, which are common contaminants in the pharmaceutical industry. A region of bacterial 16SrRNA gene was analyzed by bidirectional DNA sequencing. Bacterial identification based on partial sequencing of the 16SrRNA gene is the appropriate method that could be used in the pharmaceutical industry after adequate validations. We have successfully identified all tested bacteria with more than 99 % similarity to the already published sequences. PMID- 27279072 TI - Effect of rutin from tartary buckwheat sprout on serum glucose-lowering in animal model of type 2 diabetes. AB - This study investigates the anti-diabetic effects of rutin from tartary buckwheat sprout in type 2 diabetes mouse model. The rutin content in tartary buckwheat sprout (TBS) is five times higher than that found in common buckwheat sprout (CBS) as evident from high-performance liquid chromatography analysis. Administration of either rutin or TBS ethanolic extract to diabetes mice decreased the serum glucose level significantly. Rutin down-regulated the expression levels of protein-tyrosine phosphatase 1B; it is negative regulator of insulin pathway, both transcriptionally and translationally in myocyte C2C12 in a dose-dependent manner. In conclusion, rutin can play a critical role in down regulation of serum glucose level in type 2 diabetes. PMID- 27279073 TI - Protective effects of BMSCs in combination with erythropoietin in bronchopulmonary dysplasia-induced lung injury. AB - Bronchopulmonary dysplasia (BPD) is the most common type of chronic lung disease in infancy, for which no effective therapy is currently available. The aim of the present study was to investigate the effect of treatment with bone marrow mesenchymal stem cells (BMSCs) in combination with recombinant human erythropoietin (rHuEPO) on BPD-induced mouse lung injury, and discuss the underlying mechanism. The BPD model was established by the exposure of neonatal mice to continuous high oxygen exposure for 14 days, following which 1x106 BMSCs and 5,000 U/kg rHuEPO were injected into the mice 1 h prior to and 7 days following exposure to hyperoxia. The animals received four treatments in total (n=10 in each group). After 14 days, the body weights, airway structure, and levels of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) were detected using histological and immunohistochemical analyses. The effect on cell differentiation was observed by examining the presence of platelet endothelial cell adhesion molecule (PECAM) and VEGF using immunofluorescence. Compared with the administration of BMSCs alone, the body weight, airway structure, and the levels of MMP-9 and VEGF were significantly improved in the BMSCs/rHuEPO group. The results of the present study demonstrated that the intravenous injection of BMSCs significantly improved lung damage in the hyperoxia-exposed neonatal mouse model. Furthermore, the injection of BMSCs in combination with intraperitoneal injection of rHuEPO had a more marked effect, compared with BMSCs alone, and the mechanism may be mediated by the promoting effects of BMSCs and EPO. The results of the present study provided information, which may assist in future clinical trials. PMID- 27279074 TI - Insulin resistance increases loss of antibody to hepatitis B surface antigen in nondiabetic healthy adults. AB - The aim of this study was to evaluate the impact of insulin resistance on the persistence of a protective level of anti-HBs (hepatitis B surface antigen) in a nondiabetic general population. A cohort study was designed comprising of 38 473 Korean men and women with anti-HBs at concentrations >=10 mIU/mL, who underwent a health examination. Insulin resistance was assessed with a homoeostasis model assessment of insulin resistance (HOMA-IR). A decline in anti-HBs to <10 mIU/L during the follow-up was considered to be a loss of protective anti-HBs. Cox proportional hazard models were used to estimate the adjusted hazard ratios and 95% confidence intervals for anti-HBs loss across quintiles of HOMA-IR and insulin. We identified 20 826 incidents of loss of anti-HBs antibody during 180 522 person-years of follow-up (incident rate 11.5 per 100 person-years). Increasing HOMA-IR was positively associated with incident loss of anti-HBs. The multivariable-adjusted hazard ratios (95% confidence intervals) for incident loss of anti-HBs comparing quintiles 2-5 vs quintile 1 of HOMA-IR were 1.09 (1.04 1.14), 1.14 (1.09-1.19), 1.14 (1.09-1.19) and 1.21 (1.16-1.27), respectively. These associations were stronger in younger individuals under the age of 35 than in people 35 years of age or older (P for interaction = 0.004). The association was also more evident in subjects with higher titres (>=100 mIU/mL) of anti-HBs than in those with low titres (P for interaction < 0.001). Insulin resistance was associated with an increased risk for loss of vaccine-acquired anti-HBs in a large sample of a nondiabetic, general population, indicating a possible role of insulin resistance in vaccine-induced immunity. PMID- 27279076 TI - Global Analysis of the Impact of Deleting Trigger Factor on the Transcriptome Profile of Escherichia coli. AB - Trigger factor (TF) is a key component of prokaryotic chaperone network, which is involved various basic cellular processes such as nascent peptide folding, protein trafficking, ribosome assembly. To better understanding the physiological roles of TF, global transcriptome profiles of a variety of TF deletion mutant strains of Escherichia coli were determined. We found that deletion of the tig gene, encoding TF, led to a dramatic alteration of transcriptome profile, not only affecting the gene expression of members of the chaperone network, but also changing the levels of quite a few RNAs related to metabolism and other cellular processes. Further studies showed that this alteration was only partially recovered by knockin of TF domain-deletion mutants into the endogenous tig locus, indicating that structural integrity is crucial for the biological function of TF. Finally, by combining the transcriptome and phenotype results, a physiological mechanism underlying the impact of TF deletion on the transcriptome profile was proposed. J. Cell. Biochem. 118: 141-153, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27279075 TI - Toll-like receptor 7 affects the pathogenesis of non-alcoholic fatty liver disease. AB - Recently, a possible link between toll-like receptor 7 (TLR7) and liver disease was suggested, although it was limited to fibrosis. Based on this report, we investigated whether TLR7 has a pivotal role in non-alcoholic fatty liver disease (NAFLD). The TLR7 signaling pathway, which is activated by imiquimod (TLR7 ligand) naturally, induced autophagy and released insulin-like growth factor 1 (IGF-1) into medium from hepatocytes. Lipid accumulation induced by unsaturated fatty acid (UFA; arachidonic acid:oleic acid = 1:1) in hepatocytes, was attenuated in TLR7 and autophagy activation. Interestingly, TLR7 activation attenuated UFA-induced lipid peroxidation products, such as malondialdehyde (MDA) and 4-Hydroxy-2-Nonenal (4-HNE). To clarify a possible pathway between TLR7 and lipid peroxidation, we treated hepatocytes with MDA and 4-HNE. MDA and 4-HNE induced 2-folds lipid accumulation in UFA-treated hepatocytes via blockade of the TLR7 signaling pathway's IGF-1 release compared to only UFA-treated hepatocytes. In vivo experiments carried out with TLR7 knockout mice produced results consistent with in vitro experiments. In conclusion, TLR7 prevents progression of NAFLD via induced autophagy and released IGF-1 from liver. These findings suggest a new therapeutic strategy for the treatment of NAFLD. PMID- 27279077 TI - "... he always slaps me on my ears": the health consequences of intimate partner violence among a group of patrilineal women in Ghana. AB - Intimate partner violence has implications for women's health globally. Patrilineal women have been shown to have increased risk of experiencing intimate partner violence, yet, the health consequences of intimate partner violence in patrilineal women have not been thoroughly explored or documented. This study used qualitative in-depth interviews to explore the health effects of intimate partner violence among 15 ever-partnered Ghanaian patrilineal women. Participants attributed violence to several factors including gendered domestic relations, cultural and marital rites and alcohol use, among other factors. Abused women reported health problems such as feelings of worthlessness, sleeplessness, suicidal ideation, eye injuries, bodily weakness, hypertension, genital sores and the premature termination of pregnancy. Policy makers should pay particular attention to intimate partner violence-related health consequences in designing health interventions for abused women. PMID- 27279078 TI - Accuracy of transcutaneous bilirubin measurement in newborns after phototherapy. AB - OBJECTIVE: We tested the accuracy of transcutaneous bilirubin (TcB) measure in newborns undergoing phototherapy. STUDY DESIGN: In a prospective study of 150 term Caucasian neonates, 255 measurements of total serum bilirubin (TSB) and TcB concentration were obtained 2 h after discontinuing phototherapy. TcB measurements obtained on the forehead, sternum, abdomen and covered lower abdomen were statistically compared with the corresponding TSB. RESULT: TcB consistently underestimated TSB levels significantly. The smallest but significant difference between TSB and TcB was found on the lower abdomen. The correlation between TSB and TcB was found to be moderately close (r=0.4 to 0.5). TcB measurements were inaccurate, regardless of phototherapy technique (Bilibed, conventional phototherapy). CONCLUSION: Phototherapy significantly interferes with the accuracy of transcutaneous bilirubinometry. TcB measurements performed 2 h after stopping phototherapy were not reliable, even if they were carried out on the unexposed body area. TSB assessment remains necessary, if treatment of hyperbilirubinemia is being considered. PMID- 27279079 TI - Comparing automated vs manual leukocyte differential counts for quantifying the 'left shift' in the blood of neonates. AB - OBJECTIVE: The neutrophil 'left shift' can be measured via the immature to total (I/T) neutrophil ratio or the absolute bands per MUl using a manual differential count. It can also be measured from an automated differential count by the immature granulocyte percentage (IG%) or the absolute IG per MUl. In neonates, it is unknown if the manual or automated differential count is superior. STUDY DESIGN: We directly compared complete blood counts (CBCs) with manual and automated differential counts from infants <90 days old, and documented whether or not each neonate was infected. We developed reference intervals for I/T ratio, bands per MUl, IG% and IG per MUl using values from non-infected neonates. RESULTS: The database had 10 714 CBCs. The upper reference interval for I/T ratio was 0.29 in the first 48 h and 0.31 thereafter; bands per MUl was 3710 MUl(-1) in the first 48 h and 1785 MUl(-1) thereafter. IG% was 6.2% then 4.2%; IG per MUl was 1460 MUl(-1) then 613 MUl(-1). Statistical performances of the four methods were equivalent for identifying infection. CONCLUSIONS: We developed reference intervals for four methods of quantifying a neonate's 'left shift'. The information from automated differentials is not inferior to that from manual differentials in identifying infections, but automated differentials have the advantages of a larger sample size, being less expensive, and faster performance times. PMID- 27279081 TI - GP who was struck off for lying to police is allowed back on medical register. PMID- 27279080 TI - Genetic diversity, seasonality and transmission network of human metapneumovirus: identification of a unique sub-lineage of the fusion and attachment genes. AB - Human metapneumovirus (HMPV) is an important viral respiratory pathogen worldwide. Current knowledge regarding the genetic diversity, seasonality and transmission dynamics of HMPV among adults and children living in tropical climate remains limited. HMPV prevailed at 2.2% (n = 86/3,935) among individuals presented with acute respiratory tract infections in Kuala Lumpur, Malaysia between 2012 and 2014. Seasonal peaks were observed during the northeast monsoon season (November-April) and correlated with higher relative humidity and number of rainy days (P < 0.05). Phylogenetic analysis of the fusion and attachment genes identified the co-circulation of three known HMPV sub-lineages, A2b and B1 (30.2% each, 26/86) and B2 (20.9%, 18/86), with genotype shift from sub-lineage B1 to A2b observed in 2013. Interestingly, a previously unrecognized sub-lineage of A2 was identified in 18.6% (16/86) of the population. Using a custom script for network construction based on the TN93 pairwise genetic distance, we identified up to nine HMPV transmission clusters circulating as multiple sub epidemics. Although no apparent major outbreak was observed, the increased frequency of transmission clusters (dyads) during seasonal peaks suggests the potential roles of transmission clusters in driving the spread of HMPV. Our findings provide essential information for therapeutic research, prevention strategies, and disease outbreak monitoring of HMPV. PMID- 27279082 TI - Effects of new urban motorway infrastructure on road traffic accidents in the local area: a retrospective longitudinal study in Scotland. AB - BACKGROUND: The M74 motorway extension, Glasgow, opened in June 2011. One justification for construction was an expectation that it would reduce road traffic accidents (RTAs) on local non-motorway roads. This study evaluated the impact of the extension on the number of RTAs, stratifying by accident severity. METHODS: Data for the period 1997-2014 were extracted from a UK database of reported RTAs involving a personal injury. RTA severity was defined by the level of injury: minor, severe or fatal. RTAs were assigned to (1) the local area surrounding the motorway extension, (2) a comparator area surrounding an existing motorway or (3) a control area elsewhere in the conurbation. Interrupted time series regression with autoregressive integrated moving average (ARIMA) errors was used to determine longitudinal between-area differences in change in the number of RTAs, which might indicate an intervention effect. RESULTS: Glasgow and surrounding local authorities saw a 50.6% reduction in annual RTAs (n: 5901 to 2914) between 1997 and 2014. In the intervention area, the number of recorded RTAs decreased by 50.7% (n: 758 to 374), and that of fatal/severe RTAs by 57.4% (n: 129 to 55), with similar reductions in the comparator/control areas. The interrupted time-series analysis showed no significant between-area differences in temporal trends. The reduction of pedestrian casualties was attenuated in the intervention area relative to Glasgow and surrounding authorities. CONCLUSIONS: Reduction in RTAs was not associated with the motorway extension. Our findings suggest that in planning future investment, it should not be taken for granted that new road infrastructure alone will reduce RTAs in local areas. Urbanisation is proceeding rapidly worldwide, and evidence of infrastructure changes is lacking; this novel study provides important findings for future developments. PMID- 27279083 TI - Baseline characteristics of participants in the Kerala Diabetes Prevention Program: a cluster randomized controlled trial of lifestyle intervention in Asian Indians. AB - AIMS: To describe the baseline characteristics of participants in the Kerala Diabetes Prevention Program. METHODS: The Kerala Diabetes Prevention Program is a cluster randomized controlled trial of lifestyle intervention for prevention of Type 2 diabetes mellitus in India. Participants in the study were those aged 30 60 years who had an Indian Diabetes Risk Score >= 60 and who were without Type 2 diabetes on oral glucose tolerance test. Data on demographic, lifestyle, clinical and biochemical characteristics were collected using standardized tools. RESULTS: A total of 2586 individuals were screened with the Indian Diabetes Risk Score, of these 1529 people (59.1%) had a score >= 60, of whom 1209 (79.1%) underwent an oral glucose tolerance test. A total of 202 individuals (16.7%) had undiagnosed Type 2 diabetes and were excluded, and the remaining 1007 individuals were enrolled in the trial (control arm, n = 507; intervention arm, n = 500). The mean participant age was 46.0 +/- 7.5 years, and 47.2% were women. The mean Indian Diabetes Risk Score was 67.1 +/- 8.4. More than two-thirds (69.0%) had prediabetes and 31.0% had normal glucose tolerance. The prevalence of cardiometabolic risk factors was high, including current tobacco use (34.4% in men), current alcohol use (39.3% in men), no leisure time exercise (98.0%), no daily intake of fruit and vegetables (78.7%), family history of diabetes (47.9%), overweight or obesity (68.5%), hypertension (22.3%) and dyslipidemia (85.4%). CONCLUSIONS: The Kerala Diabetes Prevention Program recruited participants using a diabetes risk score. A large proportion of the participants had prediabetes and there were high rates of cardiometabolic risk factors. The trial will evaluate the effectiveness of lifestyle intervention in a population selected on the basis of a diabetes risk score. PMID- 27279084 TI - Mechanical Ventilation Outcomes in Patients With Pulmonary Hypertension in the United States: A National Retrospective Cohort Analysis. AB - OBJECTIVE: The outcome of patients with pulmonary arterial hypertension (PAH) who undergo mechanical ventilation is not well known. METHODS: The Nationwide Inpatient Sample for 2006 to 2012 was used to isolate patients with a diagnosis of PAH who also underwent invasive (MV) and noninvasive (NIMV) mechanical ventilation. The primary outcome was in-hospital mortality. RESULTS: The hospital records of 55 208 382 patients were studied, and there were 21 070 patients with PAH, of whom 1646 (7.8%) received MV and 834 (4.0%) received NIMV. Those receiving MV had higher mortality (39.1% vs 12.6%, P < .001) and longer hospital stays (11.9 days, interquartile range [IQR] 6.1-22.2 vs 6.7 days, IQR 3.4-11.9, P < .001) than those undergoing NIMV. Of the patients treated with MV, 4.4% also used home oxygen therapy and had similar overall mortality to those who did not use home oxygen (35.3% vs 39.1%, P = .46). Similarly, there was no relationship between home oxygen use and mortality in patients treated with NIMV (10.6% vs 12.6%, P = .48). Notably, more patients treated with NIMV used home oxygen than those treated with MV (14.4% vs 4.4%, P < .001). CONCLUSION: Patients with PAH who undergo invasive mechanical ventilation have an in-hospital mortality of 39.1%. Future work may help identify the types of patients who benefit most from advanced respiratory support in a critical care setting. PMID- 27279085 TI - Studies on regeneration of central nervous system and social ability of the earthworm Eudrilus eugeniae. AB - Earthworms are segmented invertebrates that belong to the phylum Annelida. The segments can be divided into the anterior, clitellar and posterior parts. If the anterior part of the earthworm, which includes the brain, is amputated, the worm would essentially survive even in the absence of the brain. In these brain amputee-derived worms, the nerve cord serves as the primary control center for neurological function. In this current work, we studied changes in the expression levels of anti-acetylated tubulin and serotonin as the indicators of neuro regenerative processes. The data reveal that the blastemal tissues express the acetylated tubulin and serotonin from day four and that the worm amputated at the 7th segment takes 30 days to complete the regeneration of brain. The ability of self-assemblage is one of the specific functions of the earthworm's brain. The brain amputee restored the ability of self-assemblage on the eighth day. PMID- 27279087 TI - Undetected lymph node metastases in presumed early stage NSCLC SABR patients. AB - INTRODUCTION: Stereotactic body radiation therapy (SBRT, also called stereotactic ablative body radiation SABR) is the treatment of choice for many patients with early-stage non-small cell lung cancer (NSCLC), including those who are unfit for surgery or refuse surgery. AREAS COVERED: In an effort to develop optimal staging for the evaluation of SBRT candidates, we review the performance of available lymph node staging methods, as well as risk factors for lymph node involvement. Pubmed was searched to identify relevant literature. Current staging methods for NSCLC, including Positron Emission Tomography/Computed Tomography(PET/CT) and endobronchial ultra sound (EBUS), have limited sensitivities. Expert commentary: There are several factors, including primary tumor location, tumor size, and histology that are possibly associated with the sensitivity of PET/CT to detect mediastinal lymph node metastasis. Small lymph node metastases typically remain undetected by PET/CT. Therefore invasive nodal staging procedures are indicated for most presumed early-stage NSCLC patients, but these also have limited sensitivity. Occult lymph node metastasis is associated with adverse outcome in NSCLC. Moreover, there is overwhelming evidence that certain patients who have lymph node metastases detected at the time of surgery derive an overall survival benefit from adjuvant therapies. It remains to be determined if improved detection of lymph node metastases in SABR candidates can indeed improve prognosis. PMID- 27279086 TI - How do the macrocyclic lactones kill filarial nematode larvae? AB - The macrocyclic lactones (MLs) are one of the few classes of drug used in the control of the human filarial infections, onchocerciasis and lymphatic filariasis, and the only one used to prevent heartworm disease in dogs and cats. Despite their importance in preventing filarial diseases, the way in which the MLs work against these parasites is unclear. In vitro measurements of nematode motility have revealed a large discrepancy between the maximum plasma concentrations achieved after drug administration and the amounts required to paralyze worms. Recent evidence has shed new light on the likely functions of the ML target, glutamate-gated chloride channels, in filarial nematodes and supports the hypothesis that the rapid clearance of microfilariae that follows treatment involves the host immune system. PMID- 27279088 TI - Doppler echocardiography in diastology: 35 years of Japanese contribution to its advancement and utility. AB - Echocardiography is one of the most important and clinically useful techniques in the assessment of diastolic function. Because of the prevalence of this technique, "diastology" and even the concept of diastolic heart failure have become familiar to researchers and physicians. We believe the first description by Kitabatake and his colleagues in 1982 of the use of Doppler technique to assess the transmitral flow velocity pattern in various cardiac diseases was the beginning of this development. Since then, a number of excellent works regarding echocardiographic assessment of diastolic function have emerged from Japan. Here, we review the Japanese contributions to the development of the use of Doppler echocardiography in diastology. PMID- 27279089 TI - Heterogeneity of apex-to-base dispersion in diastolic lengthening is related to impaired global left ventricular relaxation in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: The presence of apex-to-base disparity in diastolic left ventricle (LV) endocardial lengthening, based on an electromechanical activation sequence, has been recognized as an important determinant of LV diastolic properties. However, the behavior of LV apical and basal diastolic lengthening and its relationship to LV filling in hypertrophic cardiomyopathy (HCM) are unknown. METHODS: We obtained basal and apical LV short-axis views in 27 patients with non obstructive HCM and 25 healthy volunteers. The patients with HCM were subdivided into two groups; those with apical hypertrophy [APH(+)] or those without apical hypertrophy [APH(-)]. Eight equiangular points on the endo-myocardium at end diastole were placed in each view, and the movements of these points were automatically tracked using a two-dimensional echocardiographic tissue tracking system. Time-LV internal diameter curves were obtained and averaged. The time intervals from the aortic valve closure to the point of the first 40% of peak diastolic lengthening (T 40) were measured in each view. The standard deviation of the time to peak systolic circumferential shortening at the base and apex were calculated to assess the heterogeneity of LV contraction. RESULTS: The time difference in the T 40 between the apex and base (dt-T 40) in the HCM-APH(+) and HCM-APH(-) groups was greater than that in the control group. The heterogeneities in LV apical systolic shortening in the HCM groups were greater than those in the control group. There were good linear correlations between the dt-T 40 and the LV early diastolic echo-parameters and the LV mass index. CONCLUSIONS: Delayed apical relaxation and filling in patients with HCM is related to LV diastolic dysfunction and systolic dyssynchronous contraction. PMID- 27279090 TI - Diastolic stress echocardiography in Japanese elderly patients: prevalence and features of patients with elevated left ventricular filling pressure after treadmill stress. AB - PURPOSE: This study attempted to evaluate the prevalence and features of elderly patients with elevated post-exercise left ventricular (LV) filling pressure in Japan. BACKGROUND: Previous studies have validated that LV filling pressure during exercise can be estimated non-invasively by the Doppler index of diastolic filling (E/E'), and diastolic stress echocardiography has been promoted. There is limited information about diastolic stress echocardiography in Japan. METHODS: Three hundred ten elderly patients aged >=60 years who underwent treadmill stress echocardiography were studied. Patients with ischemic response were excluded. Doppler measurements were made before and immediately after the treadmill stress, and patients were divided into two groups regarding post-exercise E/E' with cutoff values of 15. Clinical and echocardiographic characteristics were compared between the two groups. RESULTS: One-third (33.9%) of the patients presented elevated post-exercise LV filling pressure indicated by E/E' >=15. Patients with an elevated post-exercise E/E' were older (p = 0.0052), had a greater mean body mass index (p = 0.0459), were more likely to have an abnormal glucose tolerance (p = 0.0059), had a greater LV mass index (p = 0.0383), a greater left atrial volume index (p = 0.0042), and a higher E/E' value at rest (p < 0.0001). CONCLUSION: One-third of the Japanese elderly patients who were referred for treadmill stress echocardiography and not limited by ischemia presented elevated post-exercise LV filling pressure indicated by E/E' >=15. These patients are likely to have clinical and echocardiographic characteristics of heart failure with preserved ejection fraction. PMID- 27279091 TI - Location of flow axis line in the left ventricle and its interaction with local myocardial motion. AB - BACKGROUND: The interaction between local myocardial motion and blood flow dynamics should be assessed to evaluate left ventricular pump function. METHODS: The contour map of the absolute value of blood flow velocity in the left ventricle (LV) was drawn. The ridgeline of the contour was defined as the "flow axis line". LV wall motion was assessed by the tracing endocardial border in consecutive B-mode images and by myocardial tissue velocity distribution obtained by the optical flow method. RESULTS: The location of the main flow axis line was affected by the local myocardial movement in the short axis direction. The flow axis line method is superior to the previous investigations on two-dimensional blood flow analysis because it considered three-dimensional blood flow. CONCLUSIONS: The flow axis line represents not only intracardiac blood flow structure but also its interaction with the cardiac wall motion. PMID- 27279092 TI - Left ventricular-right atrial communication by perforation of the atrioventricular portion of the membranous septum and severe aortic valve regurgitation caused by infective endocarditis. AB - We report the case of acquired left ventricle (LV) to right atrial (RA) communication through an aneurysm of the atrioventricular septum caused by infectious endocarditis. A severe aortic valve regurgitation and destruction of the aortic valve was detected by echocardiography. Transesophageal echocardiography revealed a flail aortic valve with vegetation and abnormal shunt flow from the LV to RA with ruptured aneurysm of the membranous septum. An abscess cavity of the aortic ring was introduced. Because of worsening congestive heart failure, the patient underwent emergency aortic valve replacement and patch closure of the communication of the membranous septum. The patient's postoperative course was uneventful. PMID- 27279093 TI - Intermittent chest pain with marked ST depression after 13 years of aortic valve replacement. AB - An 80-year-old woman who underwent aortic valve replacement with a 19-mm Medtronic Hall prosthetic valve in 1993 was admitted because of intermittent chest pain. Electrocardiography on admission revealed non-specific changes, but electrocardiography during chest pain revealed significant ST depression. Coronary angiography revealed no significant stenosis. Echocardiography revealed intermittent severe aortic regurgitation and incomplete closure of the prosthetic valve in diastole. An urgent operation was performed, and abnormal pannus formation was observed at the left ventricular side of the prosthetic valve. In this case, intermittent diastolic valvular sticking caused severe aortic regurgitation and induced serious myocardial ischemia. PMID- 27279095 TI - Octopus in a fisherman's heart. PMID- 27279094 TI - Clinical significance of coronary flow velocity measurement using transthoracic Doppler echocardiography for unstable angina: a two-case report. AB - Clinical significance of coronary flow velocity measurement by transthoracic Doppler echocardiography in 2 patients with unstable angina (UA) was reported. No significant abnormality was observed on electrocardiography. Coronary flow sequence of the left anterior descending coronary artery (LAD) was detected in diastole. Peak diastolic flow velocity was 11.1 cm/s in case 1 and 10.1 cm/s in case 2. On the basis of these data, emergency coronary angiography was performed in both cases. Severe stenosis was observed at the proximal portion of LAD; consequently, emergency coronary angioplasty was performed. Coronary flow velocity measurement is useful as a diagnostic strategy in UA. PMID- 27279096 TI - Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study. AB - A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H2 SO4 at lambdaem = 364 nm after excitation at lambdaex = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (+/- SD) of 99.96 (+/- 0.4) and 100.1 (+/- 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27279097 TI - Association Between Primary Care Visits and Colorectal Cancer Screening Outcomes in the Era of Population Health Outreach. AB - BACKGROUND: Population outreach strategies are increasingly used to improve colorectal cancer (CRC) screening. The influence of primary care on cancer screening in this context is unknown. OBJECTIVE: To assess associations between primary care provider (PCP) visits and receipt of CRC screening and colonoscopy after a positive fecal immunochemical (FIT) or fecal occult blood test (FOBT). DESIGN: Population-based cohort study. PARTICIPANTS: A total of 968,072 patients ages 50-74 years who were not up to date with CRC screening in 2011 in four integrated healthcare systems (three with screening outreach programs using FIT kits) in the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. MEASURES: Demographic, clinical, PCP visit, and CRC screening data were obtained from electronic health records and administrative databases. We examined associations between PCP visits in 2011 and receipt of FIT/FOBT, screening colonoscopy, or flexible sigmoidoscopy (CRC screening) in 2012 and follow-up colonoscopy within 3 months of a positive FIT/FOBT in 2012. We used multivariable logistic regression and propensity score models to adjust for confounding. RESULTS: Fifty-eight percent of eligible patients completed a CRC screening test in 2012, most by FIT. Those with a greater number of PCP visits had higher rates of CRC screening at all sites. Patients with >=1 PCP visit had nearly twice the adjusted-odds of CRC screening (OR = 1.88, 95 % CI: 1.86-1.89). Overall, 79.6 % of patients with a positive FIT/FOBT completed colonoscopy within 3 months. Patients with >=1 PCP visit had 30 % higher adjusted odds of completing colonoscopy after positive FIT/FOBT (OR = 1.30; 95 % CI: 1.22-1.40). CONCLUSIONS: Patients with a greater number of PCP visits had higher rates of both incident CRC screening and colonoscopy after positive FIT/FOBT, even in health systems with active population health outreach programs. In this era of virtual care and population outreach, primary care visits remain an important mechanism for engaging patients in cancer screening. PMID- 27279098 TI - Capsule Commentary on Gao, et al., Characteristics Associated with Patient Centered Medical Home Capability in Health Centers: A Cross-Sectional Analysis. PMID- 27279099 TI - Capsule commentary on Lo-Ciganic, et al., Trajectories of Diabetes Medication Adherence and Hospitalization Risk: A Retrospective Cohort Study in a Large State Medicaid Program. PMID- 27279100 TI - Capsule Commentary on Kroll et al., Benzodiazepines Are Prescribed More Frequently to Patients Already at Risk for Benzodiazepine-Related Adverse Events in Primary Care. PMID- 27279101 TI - Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro. AB - Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed. PMID- 27279103 TI - [Corrigendum] Downregulation of cytokeratin 18 is associated with paclitaxel resistance and tumor aggressiveness in prostate cancer. AB - After the publication of the article, the authors noted that they would like to add Dr Robert H. Getzenberg's name to the authors' list and as a co-corresponding author, upon the agreement of all the authors. The correct author list should be as follows: BO YIN1, MO ZHANG1, YU ZENG2,3*, YOUQIANG LI3, CHAO ZHANG1, ROBERT H. GETZENBERG3* and YONGSHENG SONG1* 1Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004; 2Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China; 3James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21087, USA Correspondence should now be addressed to: Correspondence to: Dr Yongsheng Song, Department of Urology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, Liaoning 110004, P.R. China E-mail: yinbowzf@163.com Dr Robert H. Getzenberg, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21087, USA E-mail: getzenberg@outlook.com *Contributed equally [the original article was published in the International Journal of Oncology 48: 1730-1736, 2016; DOI: 10.3892/ijo.2016.3396]. PMID- 27279104 TI - Epidemiology of hyperadrenocorticism among 210,824 dogs attending primary-care veterinary practices in the UK from 2009 to 2014. AB - OBJECTIVES: To estimate prevalence and risk factors for diagnosis with hyperadrenocorticism in dogs attending primary-care veterinary practices in the UK from 2009 to 2014. METHODS: Cases were identified by searching the de identified electronic patient records from UK primary-care veterinary practices participating in the VetCompass Programme. RESULTS: The estimated prevalence for hyperadrenocorticism diagnosis in dogs was 0.28% (95% confidence interval: 0.25 to 0.31). Multivariable logistic regression analysis revealed four associated risk factors: breed, breed-relative bodyweight, age and insurance status. The bichon frise had 6.5 times the odds (95% CI: 3.5 to 12.1, P<0.001) of hyperadrenocorticism compared with crossbreds. Dogs weighing more than or equal to their breed mean had 1.7 times the odds (95% CI: 1.3 to 2.3, P<0.001) of hyperadrenocorticism compared with dogs weighing less than the breed mean. Dogs aged 12.0 years and above showed 5.7 times the odds (95% CI: 3.7 to 8.7, P<0.001) of hyperadrenocorticism compared with dogs aged 6.0 to 8.9 years. Insured dogs had 4.0 times the odds (95% CI: 2.8 to 5.6, P<0.001) of hyperadrenocorticism compared with non-insured dogs. CLINICAL SIGNIFICANCE: This is the first epidemiological report of a non-referral hospital population of dogs diagnosed with hyperadrenocorticism in the UK and describes important breed, age and bodyweight associations with this disorder which may improve diagnosis and enhance understanding of the underlying pathophysiology. PMID- 27279105 TI - Paradigm shift in medical ultrasonography. PMID- 27279102 TI - The genetic heterogeneity of colorectal cancer predisposition - guidelines for gene discovery. AB - BACKGROUND: Colorectal cancer (CRC) is a cumulative term applied to a clinically and genetically heterogeneous group of neoplasms that occur in the bowel. Based on twin studies, up to 45 % of the CRC cases may involve a heritable component. Yet, only in 5-10 % of these cases high-penetrant germline mutations are found (e.g. mutations in APC and DNA mismatch repair genes) that result in a familial aggregation and/or an early onset of the disease. Genome-wide association studies have revealed that another ~5 % of the CRC cases may be explained by a cumulative effect of low-penetrant risk factors. Recent attempts to identify novel genetic factors using whole exome and whole genome sequencing has proven to be difficult since the remaining, yet to be discovered, high penetrant CRC predisposing genes appear to be rare. In addition, most of the moderately penetrant candidate genes identified so far have not been confirmed in independent cohorts. Based on literature examples, we here discuss how careful patient and cohort selection, candidate gene and variant selection, and corroborative evidence may be employed to facilitate the discovery of novel CRC predisposing genes. CONCLUSIONS: The picture emerges that the genetic predisposition to CRC is heterogeneous, involving complex interplays between common and rare (inter)genic variants with different penetrances. It is anticipated, however, that the use of large clinically well-defined patient and control datasets, together with improved functional and technical possibilities, will yield enough power to unravel this complex interplay and to generate accurate individualized estimates for the risk to develop CRC. PMID- 27279106 TI - Ultrasound stimulation induces microRNA expression changes that could be involved in sonication-induced apoptosis. AB - PURPOSE: The purpose of this study is to investigate the involvement of microRNAs (miRNAs) in sonication-induced apoptosis. METHODS: U937 cells derived from human leukemia were sonicated with 1-MHz ultrasound at 0.4 W/cm(2) and 10 % duty factor for 60 s, a condition inducing apoptosis. The total RNA was extracted from cells at various timings after sonication and subjected to microarray and real-time PCR for miRNA expression analyses. RESULTS: Expression of several miRNAs was significantly affected by sonication. For miR-424* and miR-720, whose expressions were eminently decreased by sonication, cell lines overexpressing these miRNAs were established. Conversely, for miR-663B and miR-663, whose expressions were eminently increased by sonication, cell lines inhibiting these miRNA functions were established. When these cell lines were sonicated, a cell line inhibiting miR-663B function significantly increased sonication-induced apoptosis, suggesting this may be involved in cellular responses to sonication. Two genes that could induce apoptosis, KSR2 and CREBZF, were identified as potential target genes of miR-663B since potential target sequences on their 3' UTR mediated to decrease expression of a reporter gene. CONCLUSION: These results suggest that miRNAs may be involved in cellular responses to ultrasound through their expression changes caused by sonication. PMID- 27279107 TI - Ultrasound findings in intersection syndrome. AB - OBJECTIVE: The purpose of our study is to demonstrate the role of ultrasound as a first-line technique in the evaluation of intersection syndrome, reporting and illustrating its typical and atypical findings. METHODS: In a 2-year period, we reviewed nine patients who received an ultrasound examination for non-specific inflammatory signs in the distal forearm: four men (28-53 years old) and five women (34-57 years old), with a mean age of 44.1 years. RESULTS: The ultrasound examination revealed, in all patients, the presence of peritendinous oedema and a small amount of synovial fluid within the tendon sheaths at the crossing intersection point between the first and the second dorsal extensor tendon compartments, with loss of the hyperechoic cleavage plane between the two tendon groups. In two patients, we observed an irregularly thickened tendon sheath, with small hyperechoic nodules within the fluid, related to proliferation of the synovial membrane. In one case, we detected a relevant thickening of the extensor carpi radialis longus and brevis tendon. Only one patient showed moderate muscle oedema within the first extensor compartment muscles, while another one had significant subcutaneous oedema. CONCLUSION: Ultrasound is effective in the first level diagnosis of intersection syndrome. PMID- 27279108 TI - Monocrotaline-induced pulmonary hypertension with sufficient tricuspid regurgitation in a rat model. AB - BACKGROUND AND PURPOSE: It is well known that monocrotaline (MCT) induces pulmonary hypertension (PH) in rats. This model is very useful for understanding the physiology of PH and developing treatments for PH. However, it is very difficult to estimate pulmonary artery pressure (PAP) in this model. The purpose of this study is to establish a PH model with sufficient tricuspid regurgitation (TR) to evaluate PAP. METHOD: We studied 17 male rats that received 15 injections of 5 mg/kg/day of MCT (PH) or vehicle (control). Three weeks after the first MCT injection, we measured left and right ventricular dimensions, the ratio of acceleration to ejection time in pulmonary flow, and the development of TR using an echocardiograph (SONOS5500) with a s12 probe (frequency: 5-12 MHz, frame rate: 120 Hz). RESULTS: The right ventricular end-diastolic area in the PH group was significantly larger than that in the control group. The acceleration time/ejection time ratio and velocity time integral of the pulmonary artery in the PH group were smaller than those in the control group. In 78 % of rats in the PH group, sufficient TR was observed and estimated PAP was 75.4 +/- 13.8 mmHg. There was a good correlation between PAP estimated by a Doppler method and directly measured right ventricular pressure (r = 0.94, P < 0.0001). CONCLUSION: Fifteen injections of 5 mg/kg/day of MCT could induce PH with sufficient TR in rats. Transthoracic echocardiography could be used for monitoring the progress of PH in the rat model. PMID- 27279109 TI - Is there any relation between umbilical artery and vein diameter and estimated fetal weight in healthy pregnant women? AB - PURPOSE: The aim of this study was to investigate the relation between umbilical vessel diameter and estimated fetal weight (EFW) and other fetal biometric parameters, and to assess the role of umbilical vessel diameter in prediction of EFW. Umbilical vein/umbilical artery (UV/UA) ratio and its relation to EFW were also examined. METHODS: A prospective study was designed to assess the sonographic diameter of UA and UV in 720 low-risk pregnant women at 20-40 weeks' gestation. Fetal biometry, EFW, and umbilical vessel measurements were performed. RESULTS: There were strong correlations between umbilical vessel diameter versus gestational age and EFW. Umbilical vessel diameters increased linearly up to 34 weeks, after which they plateaued. No relation was found between EFW versus UV/UA ratio and gestational age versus UV/UA. CONCLUSION: Based on these findings, it is not possible at present to recommend the use of umbilical vessel diameters for prediction of EFW after 34 weeks, but it may be helpful under 34 weeks. UV/UA ratio is not useful for prediction and management of complicated pregnancies. PMID- 27279110 TI - Four-year experience with prenatal diagnosis of congenital heart defects at a single referral center in Japan with focus on inaccurately diagnosed cases. AB - PURPOSE: To evaluate the accuracy of prenatal diagnosis of congenital heart defect at the referral level in our institution. METHODS: One hundred and thirty two cases were referred for prenatal diagnosis of congenital heart defect (CHD). Cases having CHDs were divided into isolated and complex CHDs, and the prenatal and postnatal diagnoses were compared. RESULTS: Thirty-nine cases were diagnosed with CHDs. The remaining 93 cases were diagnosed as normal. Postnatal diagnosis confirmed that 39 cases had CHDs; there were 19 cases of isolated CHD and 20 cases of complex CHD. Among the 19 cases of isolated CHD, all four cases with a false negative diagnosis had ventricular septal defects of an outlet or muscular type with a small defect. Cases with a false positive diagnosis had coarctation of the aorta (3 cases) or total anomalous pulmonary venous connection (1 case). Among the 20 cases of complex CHD, the prenatal diagnoses in two cases were not the same as the postnatal diagnosis and the prognosis was worse than expected. In one case with a single ventricle, pulmonary stenosis, and pulmonary venous atresia, the prenatal diagnosis was hypoplastic left heart syndrome with a suboptimal study at 38 weeks' gestation. In the other case, the diagnosis of corrected transposition of the great arteries had been missed because of misinterpretation of the anatomically right and left ventricles in utero. CONCLUSIONS: There were three possible causes of misdiagnosis or overdiagnosis of CHD: disease orientation, timing of diagnosis, and skill of the examiners. This information may be helpful for the improvement of diagnosis. PMID- 27279111 TI - Diagnosis of anal sphincter defects by three-dimensional transperineal ultrasound in women with anal incontinence. AB - PURPOSE: To assess the utility of transperineal three-dimensional (3D) ultrasound for diagnosing anal sphincter defects and evaluating the function of the anal canal in women with anal incontinence. METHODS: The study subjects were 13 women with anal incontinence. Symptoms of fecal incontinence were assessed by Wexner score. The anal canal of each woman was examined ultrasonically with both a convex transperineal 3D scanner and a radial transanal scanner to compare the accuracy of the two approaches for diagnosis of anal sphincter defects. The anorectal angle and the length of the anal canal were also measured by utilizing the functionality of the transperineal 3D ultrasound. RESULTS: The mean age was 58.9 +/- 14.9 years (+/-SD), and the mean Wexner score was 8.4 +/- 5.6. In terms of ultrasound diagnosis of anal sphincter defects, the two methods showed consistent results in each woman. The length of the portion where both the internal and external anal sphincters were intact was significantly correlated with the Wexner score, whereas the total length of the anal canal was not. CONCLUSIONS: Less invasive transperineal 3D ultrasound provides accurate evaluation of the internal and external anal sphincters in women with anal incontinence, and the method is potentially useful for detection of anal sphincter abnormalities. PMID- 27279112 TI - Analysis of the predictable variables for placenta accreta without placenta previa. AB - OBJECTIVES: To clarify the predictive variables for adherence of the placenta (AP) in cases without placenta previa. METHODS: A prospective cohort study was conducted between 2008 and 2010. Patients without placenta previa who delivered singleton babies after 36 weeks' gestation were enrolled. The maternal and ultrasonographic variables associated with AP were evaluated at the time of admission for delivery. RESULTS: A total of 2834 consecutive subjects were included. Placenta accreta without placenta previa was observed in six cases (0.2 %). Two cases in which the placenta was located on the previous uterine scar had AP, but AP was found only in 0.1 % of cases in which the placenta was not on the previous scar (p < 0.001). AP was frequently observed in cases with a history of previous uterine surgery compared to cases without a history [(1.9 vs. 0.1 %) p < 0.001]. AP was observed in 33 % of cases in which no retroplacental clear zone was detected, whereas AP was observed in only 0.1 % of cases with a clear zone (p < 0.001). CONCLUSION: A past history of uterine surgery, ultrasonographic findings of no retroplacental clear zone, and a placenta on the uterine scar were associated with AP in cases without placenta previa. PMID- 27279113 TI - Ultrasound diagnosis of fracture-separation of the distal humeral chondro epiphysis: a rare but important condition that a radiologist must not miss. AB - Fracture-separation of the distal humeral epiphysis is a rare condition known to be associated with non-accidental injury. Ultrasound is useful in diagnosis of this important disease entity with the humeral epiphysis not yet ossified. PMID- 27279114 TI - Neoadjuvant HIFU treatment for malignant fibrous histiocytoma: report of a case. AB - High-intensity focused ultrasound (HIFU) is an innovative, noninvasive, extracorporeal technique that induces coagulative necrosis of tumor tissue by thermal effects and cavitation. In published studies, HIFU has usually been used as an alternative to surgery, with or without other treatment modalities, to achieve curative tumor ablation or palliative tumor cytoreduction. Neoadjuvant HIFU treatment for primary inoperable malignant fibrous histiocytoma has never been reported, and neoadjuvant radiotherapy, chemoradiation, or chemotherapy is routinely under consideration. This is the first case in which HIFU ablation contributed as a neoadjuvant therapy to facilitate function-sparing resection, not as a replacement for surgery. It suggests that HIFU ablation may have some unique major advantages for treating inoperable huge soft-tissue sarcomas as a neoadjuvant local treatment modality, especially for patients for whom neoadjuvant chemotherapy or radiotherapy is not indicated. PMID- 27279115 TI - Serial evaluation of left ventricular contraction and relaxation in Takotsubo cardiomyopathy by 2D speckle tracking echocardiography. AB - A 78-year-old woman was referred to our hospital because of general fatigue. The electrocardiogram showed ST elevation in the I, II, aVL, and V2-V6 leads. Echocardiography showed left ventricular apical akinesis. On emergent cardiac catheterization, left ventricular basal hyperkinesis and apical akinesis without coronary artery stenosis were found. The patient was diagnosed with Takotsubo cardiomyopathy. Two-dimensional myocardial speckle tracking echocardiography was performed on admission, the 8th hospital day, and the 15th hospital day. Gradual improvement in wall motion abnormality and longitudinal peak systolic strain, peak systolic strain rate, and early diastolic strain rate from the basal to apical region of the left ventricle were observed objectively, and she achieved remission. We herein report a case of Takotsubo cardiomyopathy in which objective improvement in left ventricular contraction and relaxation was observed by 2D speckle tracking imaging and bull's eye mapping. PMID- 27279117 TI - Aortopulmonary septal defect with interrupted aortic arch in a monochorionic diamniotic twin pregnancy. AB - We report a monochorionic diamniotic twin pregnancy with prenatal diagnosis of aortopulmonary septal defect combined with type B interrupted aortic arch in one of the fetuses. The mother was referred for fetal echocardiography at 24 weeks' gestation due to suspected congenital heart disease. Prenatal echocardiography revealed a defect of 2.8 mm between the main pulmonary artery and the ascending aorta. The course of the ascending aorta was straight to the neck and head, and there was no continuity of the aortic arch after the origin of innominate and left common carotid arteries. Thus, aortopulmonary septal defect with type B interrupted aortic arch was suspected. Postnatal echocardiography confirmed the diagnosis, and surgical repair was performed on the 10th day after birth. The combination of aortopulmonary septal defect with type B interrupted aortic arch is a very rare condition that can be diagnosed by fetal echocardiographic examination in the second trimester of gestation. Prenatal diagnosis is important for the prognosis, since early surgical intervention is needed to prevent development of severe heart failure in the neonate. PMID- 27279116 TI - Extrahepatic portal vein aneurysm after orthotopic liver transplantation: a case with 9-year ultrasound observations. AB - We report a case of extrahepatic portal vein aneurysm (PVA) in the late postoperative period after orthotopic liver transplantation (OLT). A 46-year-old man underwent OLT in 2001 for treatment of hepatitis B virus-induced cirrhosis and received ultrasound follow-up for 9 years. The long-term ultrasound observations showed that the diameter of the main portal vein had progressively increased from 12 mm in 2001 to 34 mm in 2007, and then remained at 34 mm from 2007 to 2010. The patient did not show any symptoms or complications that required surgical treatment during the clinical follow-up. Our case suggests that PVA after OLT can remain without a sign of deterioration for a long time, and careful observation by ultrasound may be one of the options in the clinical management. PMID- 27279118 TI - Measurement of displacement and strain in biological tissue generated by ultrasonic dual acoustic radiation force. PMID- 27279119 TI - Gastric varices secondary to splenic vein occlusion: endoscopic color Doppler ultrasonography aids diagnosis. PMID- 27279120 TI - Prenatal diagnosis of Nager syndrome in the third trimester of pregnancy and anatomopathological correlation. AB - Nager syndrome or acrofacial dysostosis is a rare and complex malformation characterized by ear anomalies, micrognathia, radial limb hypoplasia, and absence of the thumb or other fingers. Since the original description of the syndrome in 1948, there have only been four reports of prenatal diagnoses in the literature, all during the second trimester, and only two of them had anatomopathological correlations. We describe a case of Nager syndrome that was suspected in the third trimester of gestation and confirmed postnatally through pathology. The mother was white, 27 years old, and G5P2A2, with a family history of a brother with a harelip. She was referred to our service at 33 weeks of pregnancy with an ultrasound fetal diagnosis of musculoskeletal dysplasia associated with severe micrognathia and severe polyhydramnios. Birth was by means of cesarean section because of suspected fetal distress, which resulted in extraction of a live male fetus with Apgar 1/4, weight of 1,505 g, severe mandibular hypoplasia, low-set ears, severe upper-limb shortening, and absent left thumb. Death occurred 4 h after birth. Anatomopathological examination confirmed the diagnosis of Nager syndrome. PMID- 27279121 TI - Erratum to: Comparing the in vivo sonodynamic effects of dual- and single frequency ultrasound in breast adenocarcinoma. PMID- 27279122 TI - Editor's Notes. PMID- 27279123 TI - Efficacy of nobiletin, a citrus flavonoid, in the treatment of the cardiovascular dysfunction of diabetes in rats. AB - Hyperglycemia induced oxidative stress is a prime factor for cardiovascular dysfunction (CVD) in diabetic patients. In this process matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) play important roles. Nobiletin, a polymethoxy citrus flavone, has potent MMP-2 and MMP-9 inhibitory activity in addition to antioxidant activity. We hypothesized that nobiletin due to its MMP-2 & MMP-9 inhibitory and antioxidant effects may ameliorate the cardiovascular dysfunction of diabetes. Diabetes was induced using streptozotocin (50 mg kg(-1) i.p.) in male wistar rats. Four weeks after the induction of diabetes, the rats were treated with nobiletin (10 mg kg(-1), and 25 mg kg(-1)) for a period of the following four weeks. At the end of eight weeks, hemodynamic parameters were recorded, cardiac hypertrophy was measured, and antioxidant assays, and gelatin zymography for MMP-2 & MMP-9 analysis and histopathology were performed. The vascular reactivity of the aorta was measured by recording the contractile response to phenylephrine and relaxation responses to acetylcholine. Treatment with 25 mg kg(-1) nobiletin ameliorated the hemodynamic parameters, oxidative stress, collagen level, MMP-2 and MMP-9 levels, and vascular reactivity significantly compared with vehicle treated diabetic group. Thus, this study suggests that nobiletin ameliorates the CVD of diabetes by inhibiting oxidative stress, MMP-2 & MMP-9 and can be used as a potential therapeutic approach. PMID- 27279124 TI - A diastereoselective Mannich-type reaction of alpha-fluorinated carboxylate esters: synthesis of beta-amino acids containing alpha-quaternary fluorinated carbon centers. AB - We report a diastereoselective Mannich-type reaction of alpha-alkyl, alpha-aryl, and alpha-vinyl fluoroacetates with N-tert-butylsulfinyl imines. This method provides a powerful means to access a broad range of highly functionalized beta amino acids containing alpha-fluorinated quaternary stereogenic carbon centers. We also show that the stereochemical outcome of the present reaction is highly dependent on the steric and electronic properties of the fluorocarbon nucleophiles. This protocol uses readily available starting materials, tolerates a variety of functional groups, and is operationally simple. PMID- 27279125 TI - Genetic diversity of Bartonella genotypes found in the striped field mouse (Apodemus agrarius) in Central Europe. AB - We investigated the diversity of Bartonella in Apodemus agrarius, an important rodent of peri-domestic habitats, which has spread into Europe in the past 1000 years. Spleen samples of 344 A. agrarius from Eastern Slovakia were screened for the presence of Bartonella spp. using 16S-23S rRNA internal transcribed spacer region and bacteria were detected in 9% of rodents. Based on sequencing of three housekeeping genes (gltA, rpoB and groEL) Bartonella genotypes were ascribed to the species typical for mice and voles: B. grahamii, B. taylorii and B. birtlesii. However, the study also confirmed presence of genotypes belonging to the B. clarridgeiae/B. rochalimae clade, and the B. elizabethae/B. tribocorum clade, which are not commonly found in woodland rodents. In addition, a potential recombination event between these two genotypes was noted, which highlights an important role of A. agrarius in shaping Bartonella diversity and evolution. PMID- 27279126 TI - Travel medicine physician adherence to guidelines for the emergency self treatment of malaria. AB - Few studies have examined emergency self treatment (EST) antimalarial prescribing patterns. 110 physician-members of the Travel Medicine Society of Ireland and British Global and Travel Health Association participated in this study. There was a trend towards the prescription of EST for travel to remote low-risk malaria areas; for long-term residents living in low-risk areas; and for frequent travellers to low-risk areas. This study provides insights into the use of EST in travellers' malaria. PMID- 27279127 TI - Percutaneous coronary intervention under temporary peripheral veno-arterial extracorporeal membrane oxygenation. AB - We describe the case of a 68-year old female presenting with subacute ST elevation myocardial infarction and severe depressed left ventricular ejection fraction (15%) in the presence of severe three-vessel coronary artery disease. The patient was haemodynamically stable. After heart team discussion, a percutaneous coronary intervention was performed under peripheral veno-arterial extracorporeal membrane oxygenation without complications. PMID- 27279128 TI - Prognostic implications of fluid balance in ST elevation myocardial infarction complicated by cardiogenic shock. AB - BACKGROUND: Positive fluid balance has been associated with adverse outcomes in patients admitted to general intensive care units. We analysed the relationship between a positive fluid balance and its persistence over time in terms of in hospital outcomes among ST elevation myocardial infarction (STEMI) patients complicated by cardiogenic shock. METHODS: We retrospectively studied fluid intake and output for 96 hours following hospital admission in 48 consecutive adult patients with STEMI complicated by cardiogenic shock, all undergoing primary angioplasty. Daily and accumulated fluid balance was registered at up to 96 hours following admission. The cohort was stratified into two groups based on the presence or absence of positive fluid balance on day 4. Patients' records were assessed for in-hospital adverse outcomes, as well as 30-day all-cause mortality. RESULTS: A positive fluid balance was present in 19/48 patients (40%). Patients with positive fluid balance were older and more likely to be treated by intra-aortic balloon counter-pulsation and antibiotics. These patients were more likely to develop acute kidney injury and to need new intubation and were less likely to have renal function recovery as well as successful weaning from mechanical ventilation ( p < 0.05 for all). Patients with positive fluid balance had higher 30-day mortality (68% vs. 10%; p < 0.001). In a multivariate Cox regression model, for every 1-L increase in positive fluid balance, the adjusted risk for 30-day mortality increased by 24% (hazard ratio: 1.24, 95% confidence interval: 1.07-1.42; p = 0.003). CONCLUSIONS: A positive fluid balance was strongly associated with higher 30-day mortality in STEMI complicated by cardiogenic shock. PMID- 27279129 TI - Splicing Defect in Mitochondrial Seryl-tRNA Synthetase Gene Causes Progressive Spastic Paresis Instead of HUPRA Syndrome. AB - Mitochondrial aminoacyl-tRNA synthetases are an important group of disease genes typically underlying either a disorder affecting an isolated tissue or a distinct syndrome. Missense mutations in the mitochondrial seryl-tRNA synthetase gene, SARS2, have been identified in HUPRA syndrome (hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis). We report here a homozygous splicing mutation in SARS2 in a patient with progressive spastic paresis. We show that the mutation leads to diminished levels of the synthetase in patient's fibroblasts. This has a destabilizing effect on the tRNASer(AGY) isoacceptor, but to a lesser degree than in HUPRA syndrome patients. tRNASer(UCN) is largely unaffected in both phenotypes. In conclusion, the level of tRNASer(AGY) instability may be a factor in determining tissue manifestation in patients with SARS2 mutations. This finding exemplifies the sensitivity of the nervous system to partially reduced aminoacylation, which is sufficient in other tissues to maintain respiratory chain function. PMID- 27279130 TI - Flebogamma((r)) 5 % DIF Intravenous Immunoglobulin for Replacement Therapy in Children with Primary Immunodeficiency Diseases. AB - PURPOSE: The previous studies with Flebogamma((r)) 5 % DIF intravenous immunoglobulin (IVIG) contained insufficient numbers of pediatric subjects to fully warrant a pediatric indication by the FDA. The objective of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma(r) 5 % DIF for replacement therapy in children (age 2-16) with primary immunodeficiency diseases (PIDD). METHODS: IVIG was administered at eight clinical sites to 24 subjects with well-defined PIDD at a dose of 300-800 mg/kg every 21-28 days for 12 months. The pharmacokinetics endpoint in this study was the dose-adjusted increment of the serum IgG trough levels. RESULTS: The calculated serious bacterial infection rate was 0.05/subject/year. The incidence of adverse events considered potentially related to IVIG during or within 72 h after completing an infusion was within the FDA guidance threshold of <40 % at each time point. Dose adjusted incremental IgG levels remained approximately equal to or slightly greater than pre-study IgG levels (between 800 and 1000 mg/dL throughout) when the subjects were treated with IVIG therapy other than Flebogamma((r)) DIF 5 % indicating no evidence of a different pharmacokinetic profile in this pediatric population if compared to those profiles in previous Flebogamma studies in predominately adult populations. CONCLUSIONS: Flebogamma((r)) 5 % DIF is efficacious and safe, has adequate pharmacokinetic properties, is well-tolerated, and maintains the profile of Flebogamma((r)) 5 % for the treatment of children with primary humoral immunodeficiency diseases. PMID- 27279131 TI - Admission Serum Calcium Levels Improve the GRACE Risk Score Prediction of Hospital Mortality in Patients With Acute Coronary Syndrome. AB - BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) risk score has been extensively validated to predict risk during hospitalization in patients with acute coronary syndrome (ACS). Recently, serum calcium has been suggested as an independent predictor for in-hospital mortality in patients with ST-segment elevation myocardial infarction; however, the relationship between the 2 has not been evaluated. HYPOTHESIS: The combination of GRACE risk score and serum calcium could provide better performance in risk prediction. METHODS: The study enrolled 2229 consecutive patients with ACS. Independent predictors were identified by a multivariate logistic regression model. The incremental prognostic value added by serum calcium to the GRACE score was evaluated by receiver operating characteristic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Patients in the upper quartiles of serum calcium presented with lower in-hospital mortality (odds ratios for 3 upper quartiles vs lowest quartile, respectively: 0.443, 95% confidence interval [CI]: 0.206-0.953; 0.243, 95% CI: 0.090-0.654; and 0.210, 95% CI: 0.082-0.538). Area under the curve increased significantly after adding serum calcium to the GRACE score (0.685 vs 0.746; Z = 2.617, P = 0.009). Furthermore, inclusion of serum calcium in the GRACE score enhanced NRI (0.524; P = 0.009) and IDI (0.011; P = 0.003). CONCLUSIONS: Lower serum calcium level on admission is a possible indicator of increased risk of in-hospital mortality in ACS patients. Inclusion of serum calcium in the GRACE score may lead to a more accurate prediction of this risk. Large prospective studies are needed to confirm this finding. PMID- 27279132 TI - Treatment of MRI-Diagnosed Trigeminal Peripheral Nerve Sheath Tumors by Stereotactic Radiotherapy in Dogs. AB - BACKGROUND: Stereotactic radiotherapy (SRT) is an emerging technique for treating tumors in animals. OBJECTIVES: To assess the outcome of dogs with suspected intracranial trigeminal nerve peripheral nerve sheath tumors (PNST) treated with SRT. ANIMALS: Eight dogs with presumptive PNST. METHODS: This was a retrospective study of dogs identified by searching UC Davis Veterinary Medical Teaching Hospital medical records for dogs treated with SRT for a presumed PNST. Presumptive diagnosis was based on magnetic resonance imaging. SRT was delivered in 3 dose fractions of 8 Gray (Gy) on consecutive days or every other day to a total dose of 24 Gy. RESULTS: Median disease-specific survival was 745 days (range: 99-1375 days, n = 6). No signs of acute adverse effects of radiation treatment were recorded. Late radiation effects versus tumor progression could not be confirmed histopathologically because of few animals undergoing necropsy. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides preliminary evidence that dogs with PNST benefit from SRT in terms of long-term survival. The treatment appears to be well tolerated and requires fewer anesthetic events for animals compared to full-course radiation. PMID- 27279133 TI - Syndecan-4 negatively regulates antiviral signalling by mediating RIG-I deubiquitination via CYLD. AB - Retinoic acid-inducible gene I (RIG-I) plays important roles in pathogen recognition and antiviral signalling transduction. Here we show that syndecan-4 (SDC4) is a RIG-I-interacting partner identified in a yeast two-hybrid screen. We find that SDC4 negatively regulates the RIG-I-mediated antiviral signalling in a feedback-loop control manner. The genetic evidence obtained by using knockout mice further emphasizes this biological role of SDC4 in antiviral signalling. Mechanistically, we show that SDC4 interacts with both RIG-I and deubiquitinase CYLD via its carboxyl-terminal intracellular region. SDC4 likely promotes redistribution of RIG-I and CYLD in a perinuclear pattern post viral infection, and thus enhances the RIG-I-CYLD interaction and potentiates the K63-linked deubiquitination of RIG-I. Collectively, our findings uncover a mechanism by which SDC4 antagonizes the activation of RIG-I in a CYLD-mediated deubiquitination-dependent process, thereby balancing antiviral signalling to avoid deleterious effects on host cells. PMID- 27279134 TI - Syndecans promote mycobacterial internalization by lung epithelial cells. AB - Pulmonary tuberculosis (TB) is an airborne disease caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). Alveolar epithelial cells and macrophages are the first point of contact for Mtb in the respiratory tract. However, the mechanisms of mycobacterial attachment to, and internalization by, nonprofessional phagocytes, such as epithelial cells, remain incompletely understood. We identified syndecan 4 (Sdc4) as mycobacterial attachment receptor on alveolar epithelial cells. Sdc4 mRNA expression was increased in human and mouse alveolar epithelial cells after mycobacterial infection. Sdc4 knockdown in alveolar epithelial cells or blocking with anti-Sdc4 antibody reduced mycobacterial attachment and internalization. At the molecular level, interactions between epithelial cells and mycobacteria involved host Sdc and the mycobacterial heparin-binding hemagglutinin adhesin. In vivo, Sdc1/Sdc4 double knockout mice were more resistant to Mtb colonization of the lung. Our work reveals a role for distinct Sdcs in promoting mycobacterial entry into alveolar epithelial cells with impact on outcome of TB disease. PMID- 27279135 TI - Heat shock protein 90 is involved in IL-17-mediated skin inflammation following thermal stimulation. AB - The pathogenesis of inflammatory skin diseases involves interactions between immune cells and keratinocytes, including the T helper 17 (Th17)-mediated immune response. Several chemokines [chemokine (C-X-C motif) ligand (CXCL)1, CXCL5 and CXCL8] and antimicrobial peptides [beta-defensin 1 (BD1), LL-37, S100A8 and S100A9] were transcriptionally upregulated in the keratinocyte cell line HaCaT upon stimulation with interleukin (IL)-17. Balneotherapy, the treatment of disease by bathing, is an alternative therapy that has frequently been used for the treatment of inflammatory skin diseases. Immersion in pools of thermal mineral water is often considered to have chemical, thermal, mechanical and immunomodulatory benefits. We examined the effect of thermal treatment on IL-17 mediated inflammation in a model of skin disease. As Act1 is required for IL-17 signaling and is a client protein of heat shock protein 90 (HSP90), we evaluated the effect of HSP90 inhibition on IL-17-mediated cytokine and antimicrobial peptide expression in keratinocytes following heat treatment. We found that after thermal stimulation, Act1 binding to HSP90alpha was significantly increased in the presence of IL-17 (100 ng/ml) and 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, 1 uM). Antimicrobial peptide and chemokine expression generally increased after heat treatment; Act1 knockdown and 17-AAG reversed this effect. These observations demonstrate the possible immunomodulatory effect of heat on keratinocytes during the progression of IL-17-mediated inflammatory skin diseases. PMID- 27279136 TI - MicroRNA-23a downregulates the expression of interferon regulatory factor-1 in hepatocellular carcinoma cells. AB - Interferon regulatory factor-1 (IRF-1) is a tumor-suppressor gene induced by interferon-gamma (IFNgamma) and plays an important role in the cell death of hepatocellular carcinoma (HCC). HCC tumors evade death in part by downregulating IRF-1 expression, yet the molecular mechanisms accounting for IRF-1 suppression in HCC have not yet been characterized. Previous studies have shown that microRNA 23a (miR-23a) can suppress apoptosis by targeting IRF-1. Therefore, we hypothesized that miR-23a promotes HCC growth by downregulating IRF-1. For the in vivo studies, 7 cases of resected HCC and adjacent liver samples were analyzed. For the in vitro studies, IRF-1 mRNA and protein were examined in HepG2 and Huh-7 HCC cells after IFNgamma stimulation by real-time PCR and western blotting, respectively. To determine the role of miR-23a in regulating IRF-1, HepG2 cells were transfected with an miR-23a mimic or inhibitor, and IRF-1 expression was examined. Binding of miR-23a was assessed by cloning the 528-bp human IRF-1 3' untranslated region (3'UTR) into luciferase reporter plasmid pMIR-IRF-1-3'UTR. The results showed that IRF-1 mRNA expression was downregulated in the human HCC tumor tissues compared to that in the adjacent background liver tissues. IFNgamma induced IRF-1 protein was less in the HepG2 tumor cells compared to that in the primary human hepatocytes. miR-23a expression was inversely correlated with IRF 1, and addition of the miR-23a inhibitor increased basal IRF-1 mRNA and protein. Likewise, the miR-23a mimic downregulated IFNgamma-induced IRF-1 protein expression, while the miR-23a inhibitor increased IRF-1. Furthermore, the miR-23a mimic repressed IRF-1-3'UTR reporter activity, while the miR-23a inhibitor increased the reporter activity. These results demonstrated that IRF-1 expression is downregulated in human HCC tumors compared to that noted in the background liver. miR-23a downregulates the expression of IRF-1 in HCC cells, and the IRF-1 3'UTR has an miR-23a binding site that binds miR-23a and decreases reporter activity. These findings suggest that the targeting of IRF-1 by miR-23a may be the molecular basis for IRF-1 downregulation in HCC and provide new insight into the regulation of HCC by miRNAs. PMID- 27279137 TI - Identification of insulin gene variants in neonatal diabetes. AB - OBJECTIVES: Permanent neonatal diabetes (PNDM) is caused by mutations in the genes responsible for the synthesis of different proteins that are important for the normal behavior of beta cells in the pancreas. Mutations in the insulin gene (INS) are considered as one of the causes of diabetes in neonates. This study aimed to investigate the genetic variations in the INS gene in a group of Egyptian infants diagnosed with PNDM. METHODS: We screened exons 2 and 3 with intronic boundaries of the INS gene by direct gene sequencing in 30 PNDM patients and 20 healthy controls. A detailed clinical phenotyping of the patients was carried out to specify the diabetes features in those found to carry an INS variant. RESULTS: We identified five variants (four SNPs and one synonymous variant), c(0).187 + 11T > C, c.-17-6T > A, c.*22A > C, c.*9C > T, and c.36G > A (p.A12A), with allelic frequencies of 96.7%, 80%, 75%, 5%, and 1.7%, respectively. All showed no statistically significance difference compared with the controls, with the exception of c.*22A > C. CONCLUSION: Genetic screening for the INS gene did not reveal an evident role in the diagnosis of PNDM. PMID- 27279138 TI - Ultrasonographic and cytopathological features of an inflammatory pseudonodule in the thyroid gland. AB - OBJECTIVE: No previous study has investigated the ultrasonography (US) and cytopathological features of an inflammatory pseudonodule (IFP) associated with underlying thyroiditis. This study aimed to evaluate and identify the characteristic US features of IFP in patients who underwent US-guided fine-needle aspiration (US-FNA). METHODS: From January 2012 to December 2014, 899 patients underwent US-FNA for a solid thyroid nodule that was >=5 mm in diameter, by a single radiologist. Among them, 49 nodules showed lymphocytic thyroiditis on cytological analysis. Based on cytohistopathological and follow-up US results, 28 IFP cases were included. The same radiologist and a cytopathologist retrospectively analyzed all the US images and the cytology slides, respectively. RESULTS: The locations of 28 IFPs were from the right lobe (n = 13), left lobe (n = 13), and isthmus (n = 2). The echogenicity of 28 IFPs was hypoechoic (n = 5) or marked hypoechoic (n = 23). The common US features of IFP were marked hypoechogenicity, no calcification, smooth margin, ovoid shape, and the same vascularity as adjacent parenchyma. However, no IFP cases showed calcification, spiculated margin, taller-than-wide shape, and central or peripheral vascularity. The common cytopathological feature of IFP was lymphocyte infiltration, but the intensity of this was variable, with mild, moderate, and severe intensity observed in 8 (28.6%), 11 (39.2%), and 9 (32.1%) of cases, respectively. CONCLUSION: IFP rarely showed malignant US and cytopathological features, except for marked hypoechogenicity, and these findings may be helpful for US and cytopathological diagnoses. Diagn. Cytopathol. 2016;44:725-730. (c) 2016 Wiley Periodicals, Inc. PMID- 27279140 TI - Infant digestion physiology and the relevance of in vitro biochemical models to test infant formula lipid digestion. AB - Lipids play an important role in the diet of preterm and term infants providing a key energy source and essential lipid components for development. While a lot is known about adult lipid digestion, our understanding of infant digestion physiology is still incomplete, the greatest gap being on the biochemistry of the small intestine, particularly the activity and relative importance of the various lipases active in the intestine. The literature has been reviewed to identify the characteristics of lipid digestion of preterm and term infants, but also to better understand the physiology of the infant gastrointestinal tract compared to adults that impacts the absorption of lipids. The main differences are a higher gastric pH, submicellar bile salt concentration, a far more important role of gastric lipases as well as differences at the level of the intestinal barrier. Importantly, the consequences of improper in vitro replication of gastric digestions conditions (pH and lipase specificity) are demonstrated using examples from the most recent of studies. It is true that some animal models could be adapted to study infant lipid digestion physiology, however the ethical relevance of such models is questionable, hence the development of accurate in vitro models is a must. In vitro models that combine up to date knowledge of digestion biochemistry with intestinal cells in culture are the best choice to replicate digestion and absorption in infant population, this would allow the adaptation of infant formula for a better digestion and absorption of dietary lipids by preterm and term infants. PMID- 27279139 TI - Multiplex giant magnetoresistive biosensor microarrays identify interferon associated autoantibodies in systemic lupus erythematosus. AB - High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice. PMID- 27279142 TI - Nanoscale mapping of intrinsic defects in single-layer graphene using tip enhanced Raman spectroscopy. AB - Non-gap mode tip-enhanced Raman spectroscopy (TERS) is used for the first time to successfully map the intrinsic defects in single-layer graphene with 20 nm spatial resolution. The nanoscale Raman mapping is enabled by an unprecedented near-field to far-field signal contrast of 8.5 at the Ag-coated TERS tip-apex. These results demonstrate the potential of TERS for characterisation of defects in single-layer graphene-based devices at the nanometre length-scale. PMID- 27279141 TI - Shikonin stimulates MC3T3-E1 cell proliferation and differentiation via the BMP 2/Smad5 signal transduction pathway. AB - Shikonin, the predominant naphthoquinone pigment isolated from the Chinese plant Lithospermum erythrorhizon, is anti-inflammatory, antiviral and exerts anticancer effects, amongst other biological activities. However, it is unknown whether shikonin affects bone formation. In the present study, the role of shikonin on cell proliferation was assessed via MTT assay, and shikonin was identified to markedly promote cell growth in a time- and dose-dependent manner in the MC3T3-E1 cell line. In addition, flow cytometric analysis was performed to evaluate the effect of shikonin on the cell cycle, and it was observed that shikonin markedly increased the percentage of S-phase MC3T3-E1 cells to accelerate the G1/S transition. To investigate the potential molecular mechanism by which shikonin enhances bone formation, the changes in bone morphogenic protein-2 (BMP-2), SMAD family member 5 (Smad5), runt related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC) expression levels induced by shikonin were investigated using western blot analysis and quantitative polymerase chain reaction. The results indicated that shikonin increased the BMP-2 and Smad5 mRNA levels, and upregulated Smad5 and Runx2 protein expression levels to promote osteoblast differentiation. Furthermore, ALP staining was performed, and revealed that shikonin enhanced ALP activity. These results indicate that shikonin promotes cell proliferation and differentiation of MC3T3-E1 cells via the BMP 2/Smad5 signaling pathway. PMID- 27279143 TI - Continuation maintenance therapy with S-1 in chemotherapy-naive patients with advanced squamous cell lung cancer. AB - Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naive patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer. PMID- 27279144 TI - Identification and characterization of two cleavage fragments from the Aquareovirus nonstructural protein NS80. AB - Aquareovirus species vary with respect to pathogenicity, and the nonstructural protein NS80 of aquareoviruses has been implicated in the regulation of viral replication and assembly, which can form viral inclusion bodies (VIBs) and recruit viral proteins to its VIBs in infected cells. NS80 consists of 742 amino acids with a molecular weight of approximately 80 kDa. Interestingly, a short specific fragment of NS80 has also been detected in infected cells. In this study, an approximately 58-kDa product of NS80 was confirmed in various infected and transfected cells by immunoblotting analyses using alpha-NS80C. Mutational analysis and time course expression assays indicated that the accumulation of the 58-kDa fragment was related to time and infection dose, suggesting that the fragment is not a transient intermediate of protein degradation. Moreover, another smaller fragment with a molecular mass of approximately 22 kDa was observed in transfected and infected cells by immunoblotting with a specific anti FLAG monoclonal antibody or alpha-NS80N, indicating that the 58- kDa polypeptide is derived from a specific cleavage site near the amino terminus of NS80. Additionally, different subcellular localization patterns were observed for the 22-kDa and 58-kDa fragments in an immunofluorescence analysis, implying that the two cleavage fragments of NS80 function differently in the viral life cycle. These results provide a basis for additional studies of the role of NS80 played in replication and particle assembly of the Aquareovirus. PMID- 27279145 TI - Receptor for activated C kinase 1 (RACK1) promotes the progression of OSCC via the AKT/mTOR pathway. AB - Our previous study suggested that receptor for activated C kinase 1 (RACK1) contribute to the progression of oral squamous cell carcinoma (OSCC). The aim of this study is to elucidate the mechanism by which RACK1 regulates cell growth in OSCC using in vitro and in vivo models. The effects of RACK1 knockdown with lentivirus based shRNA in stable cell lines were evaluated by Q-PCR and western blot analysis. RACK1 silencing effects on the cell cycle in OSCC cells were detected by flow cytometry and western blot analysis. The effect of RACK1 silencing on inhibiting the progression of OSCC was illustrated using a xenografted mouse model. RACK1 and relevant signaling pathways were investigated in tissues and cells using immunohistochemistry and/or western blot analysis. Stable silencing of the RACK1 gene resulted in a distinct G1 and G2 phase arrest by downregulating Cyclin B1 and Cyclin D1. Depleted RACK1 led to markedly decreased tumor volume and the expression of Ki67, CD34, and VEGF in vivo. The expression of RACK1 and p-AKT has a parallel pattern in different stages of oral carcinogenesis tissues. In addition, the protein level of RACK1 was positively correlated with p-AKT in OSCC tissue samples and cell lines. We found specific transient knockdown of RACK1 could downregulate the protein levels of p-AKT, p mTOR, and p-S6 in a dose-dependent manner. This study demonstrates that RACK1 dependent OSCC growth and survival may be related to the increased activation of the AKT/mTOR/S6 pathway. PMID- 27279146 TI - Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects. AB - In this research work, we present a simple and efficient passive microfluidic device for plasma separation from pure blood. The microdevice has been fabricated using conventional photolithography technique on a single layer of polydimethylsiloxane, and has been extensively tested on whole blood and enhanced (upto 62%) hematocrit levels of human blood. The microdevice employs elevated dimensions of about 100 MUm; such elevated dimensions ensure clog-free operation of the microdevice and is relatively easy to fabricate. We show that our microdevice achieves almost 100% separation efficiency on undiluted blood in the flow rate range of 0.3 to 0.5 ml/min. Detailed biological characterization of the plasma obtained from the microdevice is carried out by testing: proteins by ultra violet spectrophotometric method, hCG (human chorionic gonadotropin) hormone, and conducting random blood glucose test. Additionally, flow cytometry study has also been carried on the separated plasma. These tests attest to the high quality of plasma recovered. The microdevice developed in this work is an outcome of extensive experimental research on understanding the flow behavior and separation phenomenon of blood in microchannels. The microdevice is compact, economical and effective, and is particularly suited in continuous flow operations. PMID- 27279147 TI - Time-dependent loss of mitochondrial function precedes progressive histologic cartilage degeneration in a rabbit meniscal destabilization model. AB - The goals of this work were to characterize progression of osteoarthritic cartilage degeneration in a rabbit medial meniscus destabilization (MMD) model and then to use the model to identify pre-histologic disruptions in chondrocyte metabolism under chronically elevated joint contact stresses in vivo. To characterize PTOA progression, 24 rabbits received either MMD or sham surgery. Limb loading was analyzed preoperatively and at regular postoperative intervals using a Tekscan pressure-sensitive walkway. Animals were euthanized 8 (n = 8 MMD; n = 8 sham) or 26 weeks (n = 8 MMD) postoperatively for histological cartilage evaluation by an objective, semi-automated Mankin scoring routine. To examine pre histologic pathology, MMD was performed on an additional 20 rabbits, euthanized 1 (n = 9) or 4 weeks (n = 10) postoperatively. Chondrocytes were harvested fresh for measurement of mitochondrial function, an intracellular indicator of pathology after mechanical injury. Both MMD and sham surgery caused slight decreases in limb loading which returned to preoperative levels after 2 weeks. Histologically apparent cartilage damage progressed from 8 to 26 weeks after MMD. Changes in chondrocyte respiration were variable at 1 week, but by 4 weeks postoperatively chondrocyte mitochondrial function was significantly reduced. Many human injuries that lead to PTOA are relatively mild, and the cell-level mechanisms leading to disease remain unclear. We have documented PTOA progression in an animal model of subtle joint injury under continued use, and demonstrated that this model provides a realistic environment for investigation of multi-stage cellular pathology that develops prior to overt tissue degeneration and which could be targeted for disease modifying treatments. (c) 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:590-599, 2017. PMID- 27279148 TI - Mutational analysis of the Aspergillus ambient pH receptor PalH underscores its potential as a target for antifungal compounds. AB - The pal/RIM ambient pH signalling pathway is crucial for the ability of pathogenic fungi to infect hosts. The Aspergillus nidulans 7-TMD receptor PalH senses alkaline pH, subsequently facilitating ubiquitination of the arrestin PalF. Ubiquitinated PalF triggers downstream signalling events. The mechanism(s) by which PalH transduces the alkaline pH signal to PalF is poorly understood. We show that PalH is phosphorylated in a signal dependent manner, resembling mammalian GPCRs, although PalH phosphorylation, in contrast to mammalian GPCRs, is arrestin dependent. A genetic screen revealed that an ambient-exposed region comprising the extracellular loop connecting TM4-TM5 and ambient-proximal residues within TM5 is required for signalling. In contrast, substitution by alanines of four aromatic residues within TM6 and TM7 results in a weak 'constitutive' activation of the pathway. Our data support the hypothesis that PalH mechanistically resembles mammalian GPCRs that signal via arrestins, such that the relative positions of individual helices within the heptahelical bundle determines the Pro316-dependent transition between inactive and active PalH conformations, governed by an ambient-exposed region including critical Tyr259 that potentially represents an agonist binding site. These findings open the possibility of screening for agonist compounds stabilizing the inactive conformation of PalH, which might act as antifungal drugs against ascomycetes. PMID- 27279149 TI - Relationships between physical properties and sequence in silkworm silks. AB - Silk has attracted widespread attention due to its superlative material properties and promising applications. However, the determinants behind the variations in material properties among different types of silk are not well understood. We analysed the physical properties of silk samples from a variety of silkmoth cocoons, including domesticated Bombyx mori varieties and several species from Saturniidae. Tensile deformation tests, thermal analyses, and investigations on crystalline structure and orientation of the fibres were performed. The results showed that saturniid silks produce more highly-defined structural transitions compared to B. mori, as seen in the yielding and strain hardening events during tensile deformation and in the changes observed during thermal analyses. These observations were analysed in terms of the constituent fibroin sequences, which in B. mori are predicted to produce heterogeneous structures, whereas the strictly modular repeats of the saturniid sequences are hypothesized to produce structures that respond in a concerted manner. Within saturniid fibroins, thermal stability was found to correlate with the abundance of poly-alanine residues, whereas differences in fibre extensibility can be related to varying ratios of GGX motifs versus bulky hydrophobic residues in the amorphous phase. PMID- 27279150 TI - Microglia retard dengue virus-induced acute viral encephalitis. AB - Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice. In microglia-depleted mice, the DENV infection-mediated expression of antiviral cytokines and the infiltration of CD8-positive cytotoxic T lymphocytes (CTLs) was abolished. DENV infection prompted the antigen presenting cell-like differentiation of microglia, which in turn stimulated CTL proliferation and activation. These results suggest that microglial cells play a key role in facilitating antiviral immune responses against DENV infection and acute viral encephalitis. PMID- 27279151 TI - Expression of miR-199a-3p in human adipocytes is regulated by free fatty acids and adipokines. AB - Obesity is associated with a notable risk for disease, including risk of cardiovascular disorders, type 2 diabetes mellitus (T2DM) and hypertension. Adipose tissue modulates the metabolism by releasing free fatty acids (FFAs) and adipokines, including leptin, resistin, tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). Altered secretion patterns of FFAs and adipokines have been demonstrated to result in obesity-associated insulin resistance (IR) and inflammatory responses. MicroRNA-199a-3p (miR)-199a-3p expression is significantly induced in differentiated human adipose-derived mesenchymal stem cells and indicates the association with T2DM. However, the association between miR-199a-3p levels in adipocytes and obesity-associated IR, as well as inflammatory responses remains to be elucidated. The present study observed an elevation of miR-199a-3p expression level in mature human adipocytes (visceral) compared with pre-adipocytes. In addition, miR-199a-3p expression was higher in visceral adipose deposits from obese subjects. FFA, TNF-alpha, IL-6 and leptin significantly induced miR-199a-3p expression in mature human adipocytes, while resistin had the opposite effect. miR-199a-3p may represent a factor in the modulation of obesity-associated IR and inflammatory responses. PMID- 27279152 TI - Artesunate attenuates glioma proliferation, migration and invasion by affecting cellular mechanical properties. AB - Glioma is one of the most common malignant brain tumors. Current chemotherapy is far from providing satisfactory clinical outcomes for patients with glioma. More efficient drugs are urgently needed. Artesunate (ART) is clinically used as an anti-malarial agent and exhibits potent antiproliferative activity as a traditional Chinese medicine. In addition, ART has been shown to exert a profound cytotoxic effect on various tumor cell lines, presenting a novel candidate for cancer chemotherapy. However, its anticancer effect on glioma by altering cell biomechanical properties remains unclear. The present study aimed to identify the anticancer effects of ART on human glioma SHG44 cells by assessing cell proliferation, migration/invasion, the expression of claudin-1 and the biomechanical properties of ART-treated SHG44 cells. The proliferation of the SHG44 cells was assessed by MTT assay. The cell apoptosis was detected by flow cytometry. For cell migration and invasion assays, the Transwell was used. The expression of the gene claudin-1 was detected by polymerase chain reaction. The cell membrane and biomechanical properties, as targets of ART action, were investigated by atomic force microscopy (AFM). ART significantly inhibited the proliferation of SHG44 cells in a dose- and time-dependent manner. After treatment with 30 mg/l ART, the level of cell apoptosis was significantly increased (from 6.88+/-0.062 to 23.7+/-4.16%). Furthermore, the cell migration and invasion abilities of the SHG44 cells were markedly inhibited after treatment with 30 mg/l ART. Compared with the control group (0 mg/l ART), the SHG44 cells treated with 30 mg/l ART exhibited upregulated expression of claudin-1, increased adhesive force (from 2,400+/-300 to 3,600+/-500 pN), increased high connection among SHG44 cells, increased cytomembrane roughness (from 0.118+/-0.011 to 0.269+/-0.015 um) and reduced elasticity (from 23+/-8 to 3.5+/-1.1 MPa). The present study demonstrated that ART could alter the biomechanical properties of the glioma cells to inhibit cell proliferation, migration and invasion. PMID- 27279154 TI - Impact of histopathological transformation and overall survival in patients with progressive anaplastic glioma. AB - Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9years, p=0.0005) and second surgery (1.0 vs. 3.5years, p<0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4years, p=0.008) and OS (median 10.0 vs. 4.2years, p=0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population. PMID- 27279155 TI - Strong dominance of functional alleles over gene deletions in both intensely growing and deeply starved yeast cells. AB - Previous studies with diploid yeast have shown that the deletion of one allele at a single locus typically has little impact on fitness under conditions promoting fast growth. Here, we confirm and quantify this finding. The strong dominance of functional over nonfunctional alleles is predicted by the metabolic control theory which assumes that the cell is a system of metabolic fluxes and that the total metabolic rate is equivalent to fitness. To test whether these requirements are critical, we tested dominance under conditions of long-term starvation when metabolism is low and thus the metabolic activities of proteins are likely inadequate or imbalanced. More fundamentally, the central assumption of the model, that high metabolic rate translates into high fitness, appears implausible. Contrary to these conjectures, we found that the mean rate of survival of starving heterozygotes was affected only slightly more than was the mean rate of growth under good conditions. Under none of the two treatments the central prediction of the model, that fitness of heterozygous strains is higher for the enzymatic proteins than for nonenzymatic ones, was confirmed. Our data add to growing uncertainty whether the metabolic control theory is sufficient to explain the remarkable ubiquity of strong genetic dominance. PMID- 27279153 TI - The applications of the novel polymeric fluoropyrimidine F10 in cancer treatment: current evidence. AB - F10 is a novel polymeric fluoropyrimidine drug candidate with strong anticancer activity in multiple preclinical models. F10 has strong potential for impacting cancer treatment because it displays high cytotoxicity toward proliferating malignant cells with minimal systemic toxicities thus providing an improved therapeutic window relative to traditional fluoropyrimidine drugs, such as 5 fluorouracil. F10 has a unique mechanism that involves dual targeting of thymidylate synthase and Top1. In this review, the authors provide an overview of the studies that revealed the novel aspects of F10's cytotoxic mechanism and summarize results obtained in preclinical models of acute myeloid leukemia, acute lymphocytic leukemia, glioblastoma and prostate cancer that demonstrate the strong potential of F10 to improve treatment outcomes. PMID- 27279156 TI - Axial level-dependent molecular and cellular mechanisms underlying the genesis of the embryonic neural plate. AB - The transcription factor gene Sox2, centrally involved in neural primordial regulation, is activated by many enhancers. During the early stages of embryonic development, Sox2 is regulated by the enhancers N2 and N1 in the anterior neural plate (ANP) and posterior neural plate (PNP), respectively. This differential use of the enhancers reflects distinct regulatory mechanisms underlying the genesis of ANP and PNP. The ANP develops directly from the epiblast, triggered by nodal signal inhibition, and via the combined action of TFs SOX2, OTX2, POU3F1, and ZIC2, which promotes the the ANP development and inhibits other cell lineages. In contrast, the PNP is derived from neuromesodermal bipotential axial stem cells that develop into the neural plate when Sox2 is activated by the N1 enhancer, whereas they develop into the paraxial mesoderm when the N1 enhancer is repressed by the action of TBX6. The axial stem cells are maintained by the activity of WNT3a and T (Brachyury). However, at axial levels more anterior to the 8th somites (cervical levels), the development of both the neural plate and somite proceeds in the absence of WNT3a, T, or TBX6. These observations indicate that distinct molecular and cellular mechanisms determine neural plate genesis based on the axial level, and contradict the classical concept of the term "neural induction," which assumes a pan-neural plate mechanism. PMID- 27279157 TI - [Effects of Gut Microbiota on Stress Response and Behavioral Phenotype of the Host]. AB - Gut microbiota are involved in host patho-physiological functions; however, little is known about whether or not they can affect brain function. Several recent works including ours have shown that gut microbiota play a critical role in the determination of stress response and behavioral phenotype of the host. We here review recent advances in this area, i.e. the interaction between gut microbiota and the brain-gut axis, based on our series of experimental data. PMID- 27279158 TI - [Irritable Bowel Syndrome, Emotion Regulation, and Gut Microbiota]. AB - Irritable bowel syndrome (IBS) is defined as a representative functional gastrointestinal disorder which is characterized by chronic or recurrent abdominal pain and/or abdominal discomfort associated with abnormal bowel movement. Gut microbiota are related to the pathophysiology of IBS. In the field of IBS, post-infectious etiology, stress-induced alteration of microbiota, increased mucosal permeability, bacterial overgrowth, disease-specific microbiota, microbial products, and brain-gut interactions are being investigated. In some individuals, IBS develops after recovery from acute gastroenteritis known as post-infectious IBS. Gut microbiota in IBS patients differ from those in healthy individuals, and the profiles of gut microbiota in IBS patients also vary among IBS patients with constipation, diarrhea, and mixed subtypes. In Japan, gut microbiota in IBS patients also differ from those observed in healthy individuals, and organic acid by-products observed in the patients correlated with symptoms, quality of life, and alexithymia. Further research on gut microbiota in IBS patients is warranted. PMID- 27279159 TI - [Multiple Sclerosis and Commensal Gut Flora]. AB - Although a symbiotic relationship between commensal gut microbiota and host is widely appreciated, recent works have indicated that normal gut flora functions to prevent inflammatory bowel diseases and obesity in the host, indicating a more mutualistic relationship. Dysbiosis of the commensal flora may lead to development of these disorders. Studies using experimental auto immune encephalomyelitis (EAE), a rodent model for studying multiple sclerosis (MS), revealed that onset of MS may be triggered by dysbiosis in the gut. We recently revealed a significant reduction in certain clostridia strains, which probably function to induce regulatory T cells, in the gut microbiota of patients with MS. Results from this study should be consideved when designing strategies for the prevention and treatment of MS. PMID- 27279160 TI - [Autism and Autism-associated Metabolites]. AB - Gene-microbiota interactions are now proposed to be a special case of gene environmental interaction. Preclinical and clinical data summarized in this article reveal that a specific serum metabolite, associated with alterations in gut microbiome composition, might have an emerging role in the onset and pathogenesis of autism. Altered level of this specified metabolite may induce perturbations in the epigenome and modulate the expression of key disease susceptible genes in neurons and their associated cells during critical periods of neurodevelopment. The gut microbiota itself is now regarded as a reservoir for environmental epigenetic factors. PMID- 27279161 TI - [The Importance of Vagus Nerve Afferent in the Formation of Emotions in Attention Deficit Hyperactivity Disorder Model Rat]. AB - It is of interest to know how environmental stimuli contribute to the formation of emotion during development. In a rat model of attention-deficit hyperactivity disorder, monosodium L- glutamate (MSG), a taste substance of umami, was administered for 5 weeks during developmental period, followed by emotional behavior tests such as open-field test and social interaction test in adulthood. Although no significant change was observed in anxiety-like behavior, MSG intake caused a reduction in aggressive behavior. Vagotomy under the level of diaphragm resulted in eliminating the MSG effect on aggression, indicating the importance of neuronal activity of the vagus nerve in this effect. Futher studies will focus on futher questions regarding the gut-brain axis such as the change of microbiota and the mechanism of the axis in the brain. PMID- 27279162 TI - [Depressive Disorder and Gut-brain Interaction]. AB - Depressive disorder is a stress-induced condition, which has been suggested to have bidirectional interactions with the gut microbiota. Probiotics such as Bifidobacterium and Lactobacillus have been suggested to mitigate stress response. Irritable bowel syndrome (IBS) is a typical phenotype of psychological distress manifested in the gastrointestinal system, and often develops in patients with depressive disorder. The altered gut microbiota and resultant inflammation in the gut play an important role in at least a portion of IBS. Animal models of depression have shown abnormalities in the gut such as increased gut permeability, and the probiotics ameliorate their chronic depression-like behaviors and altered stress responses. There have been only a few studies that have directly investigated the gut microbiota in patients with depression. We reported results suggesting that individuals with lower bacterial counts for Bifidobacterium and/or Lactobacillus are more common in patients with major depressive disorder than in healthy controls. the collectively use of gut microbiota in the diagnosis and treatment of depressive disorder seems to be a promising approach. PMID- 27279163 TI - [The Bridge between Pediatric and Adult Neurology]. AB - Pediatric and adult departments are differentiated based on a cutoff age of approximately 15-17 years. In clinical neurology, there are certain disorders and related problems that overlap these age-determined boundaries. In this review, the following three themes are discussed. (1) Manual dexterity: Considering motor skills through the developmental stages of a child and manual impairment due to localized brain damage in adults, manual dexterity has been reviewed extensively from the perspective of cortical association areas. (2) Hepatolenticular degeneration: Wilson's disease (children) and Westphal-Strumpell pseudosclerosis (adults) are compared and assessed based on the age of onset to identify differences in clinical symptoms and pathological findings. (3) Hirayama disease: This disease has been identified as an adult neurological disorder. Since the onset of Hirayama disease occurs around puberty in children and adolescents, it provides a connecting link between pediatric and adult neurology. PMID- 27279164 TI - [Continued Use of Rotigotine Transdermal Patches for Parkinson Disease]. AB - Transdermal patches containing rotigotine, a dopamine agonist (DA) for treatment of Parkinson disease, continuously exert stable effects when applied once daily. Therefore, they are expected to reduce the patient burdens due to complications such as wearing-off and dysphagia. However, dosing is occasionally reduced or discontinued after application because of several reasons such as skin reactions or unsatisfactory efficacy. To identify the risk factors involved in the reduced or discontinued use of rotigotine patches, a retrospective study was conducted with reference to the medical records of patients with Parkinson disease who received rotigotine patches in our hospital. 85 patients were involved in this study. Dosing of rotigotine was reduced or discontinued in 53 patients during the study period. The factors associated with charges in treatment included combination therapy with clonazepam and oral administration of another DA before the application of rotigotine. The reduction or discontinuation rate of rotigotine patches in patients who reduced the equivalent dose of DA on the introduction of rotigotine patches was 94.7%, showing a significantly higher rate compared with 61.3% in the increased dose group. To improve adherence to rotigotine patch therapy, physicians need to carefully consider concomitant drugs and total dose of DAs. (Received December 7, 2015; Accepted February 22, 2016; Published June 1, 2016). PMID- 27279165 TI - [An Extremely Rare Case of Penetrating Head Injury Caused by a Nasal Implant Made of an Ivory Chip and a Review of the Literature]. AB - Although penetrating head injuries are very rare in Japan, an extremely rare case is reported in which an ivory chip, embedded in the subcutaneous tissue by a cosmetic rhinoplasty, penetrated the cranium. A 69-year-old woman with a psychiatric disorder suddenly jumped down from a window and bruised her face. The ivory chip went into her left frontal lobe via the frontal sinus. At surgery, it was completely removed via the nasion. There were no postoperative complications after adequate frontal sinus repair and closure of dura mater with a piece of pericranium. The literature dealing with Japanese penetrating head injuries was also reviewed. (Received May 27, 2015; Accepted December 1, 2015; Published June 1, 2016). PMID- 27279166 TI - [A Case of Inspiration Stridor in Dementia with Lewy Bodies]. PMID- 27279167 TI - Climate-driven vital rates do not always mean climate-driven population. AB - Current climatic changes have increased the need to forecast population responses to climate variability. A common approach to address this question is through models that project current population state using the functional relationship between demographic rates and climatic variables. We argue that this approach can lead to erroneous conclusions when interpopulation dispersal is not considered. We found that immigration can release the population from climate-driven trajectories even when local vital rates are climate dependent. We illustrated this using individual-based data on a trans-equatorial migratory seabird, the Scopoli's shearwater Calonectris diomedea, in which the variation of vital rates has been associated with large-scale climatic indices. We compared the population annual growth rate lambdai , estimated using local climate-driven parameters with rhoi , a population growth rate directly estimated from individual information and that accounts for immigration. While lambdai varied as a function of climatic variables, reflecting the climate-dependent parameters, rhoi did not, indicating that dispersal decouples the relationship between population growth and climate variables from that between climatic variables and vital rates. Our results suggest caution when assessing demographic effects of climatic variability especially in open populations for very mobile organisms such as fish, marine mammals, bats, or birds. When a population model cannot be validated or it is not detailed enough, ignoring immigration might lead to misleading climate-driven projections. PMID- 27279168 TI - (1)H-detected solid-state NMR of proteins entrapped in bioinspired silica: a new tool for biomaterials characterization. AB - Proton-detection in solid-state NMR, enabled by high magnetic fields (>18 T) and fast magic angle spinning (>50 kHz), allows for the acquisition of traditional (1)H-(15)N experiments on systems that are too big to be observed in solution. Among those, proteins entrapped in a bioinspired silica matrix are an attractive target that is receiving a large share of attention. We demonstrate that (1)H detected SSNMR provides a novel approach to the rapid assessment of structural integrity in proteins entrapped in bioinspired silica. PMID- 27279169 TI - Six Hours after Infection, the Metabolic Changes Induced by WSSV Neutralize the Host's Oxidative Stress Defenses. AB - Levels of intracellular ROS (reactive oxygen species) were significantly increased in hemocytes collected from WSSV-infected shrimp within the first 30 120 min after infection. Measurement of the NADPH/NADP(+) and GSH/GSSG ratios revealed that after a significant imbalance toward the oxidized forms at 2 hpi, redox equilibrium was subsequently restored. Meanwhile, high levels of lactic acid production, elevated NADH/NAD(+) ratios, and metabolic changes in the glycolysis pathway show that the Warburg effect was triggered by the virus. The timing of these changes suggests that WSSV uses this metabolic shift into aerobic glycolysis to counteract the high levels of ROS produced in response to viral infection. We further show that if the Warburg effect is inhibited by chemical inhibition of the PI3K-Akt-mTOR signaling pathway, or if the pentose phosphate pathway is chemically inhibited, then in both cases, the production of intracellular ROS is sustained. We conclude that WSSV uses the PI3K-Akt-mTOR regulated Warburg effect to restore host redox balance and to counter the ROS produced by the host in response to WSSV infection. We also found that pyruvate kinase activity was inhibited by WSSV. This inhibition is likely to increase the availability of the raw materials essential for WSSV gene expression and replication. PMID- 27279171 TI - Humanity's forgotten family. PMID- 27279170 TI - 3D-Microarchitectural patterns of Hyperostosis frontalis interna: a micro computed tomography study in aged women. AB - Although seen frequently during dissections and autopsies, Hyperostosis frontalis interna (HFI) - a morphological pattern of the frontal bone thickening - is often ignored and its nature and development are not yet understood sufficiently. Current macroscopic classification defines four grades/stages of HFI based on the morphological appearance and size of the affected area; however, it is unclear if these stages also depict the successive phases in the HFI development. Here we assessed 3D-microarchitecture of the frontal bone in women with various degrees of HFI expression and in an age- and sex-matched control group, hypothesizing that the bone microarchitecture bears imprints of the pathogenesis of HFI and may clarify the phases of its development. Frontal bone samples were collected during routine autopsies from 20 women with HFI (age: 69.9 +/- 11.1 years) and 14 women without HFI (age: 74.1 +/- 9.7 years). We classified the HFI samples into four groups, each group demonstrating different macroscopic type or stage of HFI. All samples were scanned by micro-computed tomography to evaluate 3D bone microarchitecture in the following regions of interest: total sample, outer table, diploe and inner table. Our results revealed that, compared to the control group, the women with HFI showed a significantly increased bone volume fraction in the region of diploe, along with significantly thicker and more plate-like shaped trabeculae and reduced trabecular separation and connectivity density. Moreover, the inner table of the frontal bone in women with HFI displayed significantly increased total porosity and mean pore diameter compared to controls. Microstructural reorganization of the frontal bone in women with HFI was also reflected in significantly higher porosity and lower bone volume fraction in the inner vs. outer table due to an increased number of pores larger than 100 MUm. The individual comparisons between the control group and different macroscopic stages of HFI revealed significant differences only between the control group and the morphologically most pronounced type of HFI. Our microarchitectural findings demonstrated clear differences between the HFI and the control group in the region of diploe and the inner table. Macroscopic grades of HFI could not be distinguished at the level of bone microarchitecture and their consecutive nature cannot be supported. Rather, our study suggests that only two different types of HFI (moderate and severe HFI) have microstructural justification and should be considered further. It is essential to record HFI systematically in human postmortem subjects to provide more data on the mechanisms of its development. PMID- 27279172 TI - Second chances. PMID- 27279173 TI - Energy hit. PMID- 27279174 TI - Gene editing can drive science to openness. PMID- 27279186 TI - Massive ocean-observing project launches - despite turmoil. PMID- 27279187 TI - Fairer way to distribute last-ditch drugs gets real-world trial. PMID- 27279188 TI - Peru's gold rush prompts public-health emergency. PMID- 27279189 TI - Plan to synthesize human genome triggers mixed response. PMID- 27279190 TI - UK government slammed for losing track of its own research. PMID- 27279191 TI - 'Hobbit' relatives found after ten-year hunt. PMID- 27279192 TI - Correction. PMID- 27279193 TI - Can Delhi save itself from its toxic air? PMID- 27279194 TI - The man who can map the chemicals all over your body. PMID- 27279195 TI - Misconduct: Lessons from researcher rehab. PMID- 27279199 TI - Five-Year Plan: Supervise Chinese environment policy. PMID- 27279200 TI - China's primates: preserve wild species. PMID- 27279201 TI - Correction. PMID- 27279202 TI - Elephant poaching: Track the impact of Kenya's ivory burn. PMID- 27279203 TI - Butterflies: Change of identity is not in the air. PMID- 27279204 TI - China's primates: EU can't have it all ways. PMID- 27279205 TI - Ilkka Hanski (1953-2016). PMID- 27279206 TI - Host-microbe interaction: Rules of the game for microbiota. PMID- 27279207 TI - Geochemistry: Hydrogen and oxygen in the deep Earth. PMID- 27279208 TI - Evolutionary biology: To mimicry and back again. PMID- 27279209 TI - Physiology: Microbial signals to the brain control weight. PMID- 27279210 TI - Chemistry: No turning back for motorized molecules. PMID- 27279211 TI - Palaeoanthropology: The dawn of Homo floresiensis. PMID- 27279212 TI - Accounting for reciprocal host-microbiome interactions in experimental science. AB - Mammals are defined by their metagenome, a combination of host and microbiome genes. This knowledge presents opportunities to further basic biology with translation to human diseases. However, the now-documented influence of the metagenome on experimental results and the reproducibility of in vivo mammalian models present new challenges. Here we provide the scientific basis for calling on all investigators, editors and funding agencies to embrace changes that will enhance reproducible and interpretable experiments by accounting for metagenomic effects. Implementation of new reporting and experimental design principles will improve experimental work, speed discovery and translation, and properly use substantial investments in biomedical research. PMID- 27279213 TI - Midbrain circuits for defensive behaviour. AB - Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders. PMID- 27279214 TI - Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome. AB - Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient-gut microbiota interaction and subsequent parasympathetic activation as possible therapeutic targets for obesity. PMID- 27279215 TI - Cold, clumpy accretion onto an active supermassive black hole. AB - Supermassive black holes in galaxy centres can grow by the accretion of gas, liberating energy that might regulate star formation on galaxy-wide scales. The nature of the gaseous fuel reservoirs that power black hole growth is nevertheless largely unconstrained by observations, and is instead routinely simplified as a smooth, spherical inflow of very hot gas. Recent theory and simulations instead predict that accretion can be dominated by a stochastic, clumpy distribution of very cold molecular clouds--a departure from the 'hot mode' accretion model--although unambiguous observational support for this prediction remains elusive. Here we report observations that reveal a cold, clumpy accretion flow towards a supermassive black hole fuel reservoir in the nucleus of the Abell 2597 Brightest Cluster Galaxy (BCG), a nearby (redshift z = 0.0821) giant elliptical galaxy surrounded by a dense halo of hot plasma. Under the right conditions, thermal instabilities produce a rain of cold clouds that fall towards the galaxy's centre, sustaining star formation amid a kiloparsec scale molecular nebula that is found at its core. The observations show that these cold clouds also fuel black hole accretion, revealing 'shadows' cast by the molecular clouds as they move inward at about 300 kilometres per second towards the active supermassive black hole, which serves as a bright backlight. Corroborating evidence from prior observations of warmer atomic gas at extremely high spatial resolution, along with simple arguments based on geometry and probability, indicate that these clouds are within the innermost hundred parsecs of the black hole, and falling closer towards it. PMID- 27279216 TI - Digitized adiabatic quantum computing with a superconducting circuit. AB - Quantum mechanics can help to solve complex problems in physics and chemistry, provided they can be programmed in a physical device. In adiabatic quantum computing, a system is slowly evolved from the ground state of a simple initial Hamiltonian to a final Hamiltonian that encodes a computational problem. The appeal of this approach lies in the combination of simplicity and generality; in principle, any problem can be encoded. In practice, applications are restricted by limited connectivity, available interactions and noise. A complementary approach is digital quantum computing, which enables the construction of arbitrary interactions and is compatible with error correction, but uses quantum circuit algorithms that are problem-specific. Here we combine the advantages of both approaches by implementing digitized adiabatic quantum computing in a superconducting system. We tomographically probe the system during the digitized evolution and explore the scaling of errors with system size. We then let the full system find the solution to random instances of the one-dimensional Ising problem as well as problem Hamiltonians that involve more complex interactions. This digital quantum simulation of the adiabatic algorithm consists of up to nine qubits and up to 1,000 quantum logic gates. The demonstration of digitized adiabatic quantum computing in the solid state opens a path to synthesizing long range correlations and solving complex computational problems. When combined with fault-tolerance, our approach becomes a general-purpose algorithm that is scalable. PMID- 27279217 TI - Metastable high-entropy dual-phase alloys overcome the strength-ductility trade off. AB - Metals have been mankind's most essential materials for thousands of years; however, their use is affected by ecological and economical concerns. Alloys with higher strength and ductility could alleviate some of these concerns by reducing weight and improving energy efficiency. However, most metallurgical mechanisms for increasing strength lead to ductility loss, an effect referred to as the strength-ductility trade-off. Here we present a metastability-engineering strategy in which we design nanostructured, bulk high-entropy alloys with multiple compositionally equivalent high-entropy phases. High-entropy alloys were originally proposed to benefit from phase stabilization through entropy maximization. Yet here, motivated by recent work that relaxes the strict restrictions on high-entropy alloy compositions by demonstrating the weakness of this connection, the concept is overturned. We decrease phase stability to achieve two key benefits: interface hardening due to a dual-phase microstructure (resulting from reduced thermal stability of the high-temperature phase); and transformation-induced hardening (resulting from the reduced mechanical stability of the room-temperature phase). This combines the best of two worlds: extensive hardening due to the decreased phase stability known from advanced steels and massive solid-solution strengthening of high-entropy alloys. In our transformation-induced plasticity-assisted, dual-phase high-entropy alloy (TRIP DP-HEA), these two contributions lead respectively to enhanced trans-grain and inter-grain slip resistance, and hence, increased strength. Moreover, the increased strain hardening capacity that is enabled by dislocation hardening of the stable phase and transformation-induced hardening of the metastable phase produces increased ductility. This combined increase in strength and ductility distinguishes the TRIP-DP-HEA alloy from other recently developed structural materials. This metastability-engineering strategy should thus usefully guide design in the near-infinite compositional space of high-entropy alloys. PMID- 27279218 TI - Strongly correlated perovskite fuel cells. AB - Fuel cells convert chemical energy directly into electrical energy with high efficiencies and environmental benefits, as compared with traditional heat engines. Yttria-stabilized zirconia is perhaps the material with the most potential as an electrolyte in solid oxide fuel cells (SOFCs), owing to its stability and near-unity ionic transference number. Although there exist materials with superior ionic conductivity, they are often limited by their ability to suppress electronic leakage when exposed to the reducing environment at the fuel interface. Such electronic leakage reduces fuel cell power output and the associated chemo-mechanical stresses can also lead to catastrophic fracture of electrolyte membranes. Here we depart from traditional electrolyte design that relies on cation substitution to sustain ionic conduction. Instead, we use a perovskite nickelate as an electrolyte with high initial ionic and electronic conductivity. Since many such oxides are also correlated electron systems, we can suppress the electronic conduction through a filling-controlled Mott transition induced by spontaneous hydrogen incorporation. Using such a nickelate as the electrolyte in free-standing membrane geometry, we demonstrate a low-temperature micro-fabricated SOFC with high performance. The ionic conductivity of the nickelate perovskite is comparable to the best-performing solid electrolytes in the same temperature range, with a very low activation energy. The results present a design strategy for high-performance materials exhibiting emergent properties arising from strong electron correlations. PMID- 27279219 TI - An autonomous chemically fuelled small-molecule motor. AB - Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9 fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9 fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology. PMID- 27279220 TI - FeO2 and FeOOH under deep lower-mantle conditions and Earth's oxygen-hydrogen cycles. AB - The distribution, accumulation and circulation of oxygen and hydrogen in Earth's interior dictate the geochemical evolution of the hydrosphere, atmosphere and biosphere. The oxygen-rich atmosphere and iron-rich core represent two end members of the oxygen-iron (O-Fe) system, overlapping with the entire pressure temperature-composition range of the planet. The extreme pressure and temperature conditions of the deep interior alter the oxidation states, spin states and phase stabilities of iron oxides, creating new stoichiometries, such as Fe4O5 (ref. 5) and Fe5O6 (ref. 6). Such interactions between O and Fe dictate Earth's formation, the separation of the core and mantle, and the evolution of the atmosphere. Iron, in its multiple oxidation states, controls the oxygen fugacity and oxygen budget, with hydrogen having a key role in the reaction of Fe and O (causing iron to rust in humid air). Here we use first-principles calculations and experiments to identify a highly stable, pyrite-structured iron oxide (FeO2) at 76 gigapascals and 1,800 kelvin that holds an excessive amount of oxygen. We show that the mineral goethite, FeOOH, which exists ubiquitously as 'rust' and is concentrated in bog iron ore, decomposes under the deep lower-mantle conditions to form FeO2 and release H2. The reaction could cause accumulation of the heavy FeO2-bearing patches in the deep lower mantle, upward migration of hydrogen, and separation of the oxygen and hydrogen cycles. This process provides an alternative interpretation for the origin of seismic and geochemical anomalies in the deep lower mantle, as well as a sporadic O2 source for the Great Oxidation Event over two billion years ago that created the present oxygen-rich atmosphere. PMID- 27279221 TI - Homo floresiensis-like fossils from the early Middle Pleistocene of Flores. AB - The evolutionary origin of Homo floresiensis, a diminutive hominin species previously known only by skeletal remains from Liang Bua in western Flores, Indonesia, has been intensively debated. It is a matter of controversy whether this primitive form, dated to the Late Pleistocene, evolved from early Asian Homo erectus and represents a unique and striking case of evolutionary reversal in hominin body and brain size within an insular environment. The alternative hypothesis is that H. floresiensis derived from an older, smaller-brained member of our genus, such as Homo habilis, or perhaps even late Australopithecus, signalling a hitherto undocumented dispersal of hominins from Africa into eastern Asia by two million years ago (2 Ma). Here we describe hominin fossils excavated in 2014 from an early Middle Pleistocene site (Mata Menge) in the So'a Basin of central Flores. These specimens comprise a mandible fragment and six isolated teeth belonging to at least three small-jawed and small-toothed individuals. Dating to ~0.7 Ma, these fossils now constitute the oldest hominin remains from Flores. The Mata Menge mandible and teeth are similar in dimensions and morphological characteristics to those of H. floresiensis from Liang Bua. The exception is the mandibular first molar, which retains a more primitive condition. Notably, the Mata Menge mandible and molar are even smaller in size than those of the two existing H. floresiensis individuals from Liang Bua. The Mata Menge fossils are derived compared with Australopithecus and H. habilis, and so tend to support the view that H. floresiensis is a dwarfed descendent of early Asian H. erectus. Our findings suggest that hominins on Flores had acquired extremely small body size and other morphological traits specific to H. floresiensis at an unexpectedly early time. PMID- 27279222 TI - Age and context of the oldest known hominin fossils from Flores. AB - Recent excavations at the early Middle Pleistocene site of Mata Menge in the So'a Basin of central Flores, Indonesia, have yielded hominin fossils attributed to a population ancestral to Late Pleistocene Homo floresiensis. Here we describe the age and context of the Mata Menge hominin specimens and associated archaeological findings. The fluvial sandstone layer from which the in situ fossils were excavated in 2014 was deposited in a small valley stream around 700 thousand years ago, as indicated by (40)Ar/(39)Ar and fission track dates on stratigraphically bracketing volcanic ash and pyroclastic density current deposits, in combination with coupled uranium-series and electron spin resonance dating of fossil teeth. Palaeoenvironmental data indicate a relatively dry climate in the So'a Basin during the early Middle Pleistocene, while various lines of evidence suggest the hominins inhabited a savannah-like open grassland habitat with a wetland component. The hominin fossils occur alongside the remains of an insular fauna and a simple stone technology that is markedly similar to that associated with Late Pleistocene H. floresiensis. PMID- 27279223 TI - Environmental Breviatea harbour mutualistic Arcobacter epibionts. AB - Breviatea form a lineage of free living, unicellular protists, distantly related to animals and fungi. This lineage emerged almost one billion years ago, when the oceanic oxygen content was low, and extant Breviatea have evolved or retained an anaerobic lifestyle. Here we report the cultivation of Lenisia limosa, gen. et sp. nov., a newly discovered breviate colonized by relatives of animal-associated Arcobacter. Physiological experiments show that the association of L. limosa with Arcobacter is driven by the transfer of hydrogen and is mutualistic, providing benefits to both partners. With whole-genome sequencing and differential proteomics, we show that an experimentally observed fitness gain of L. limosa could be explained by the activity of a so far unknown type of NAD(P)H-accepting hydrogenase, which is expressed in the presence, but not in the absence, of Arcobacter. Differential proteomics further reveal that the presence of Lenisia stimulates expression of known 'virulence' factors by Arcobacter. These proteins typically enable colonization of animal cells during infection, but may in the present case act for mutual benefit. Finally, re-investigation of two currently available transcriptomic data sets of other Breviatea reveals the presence and activity of related hydrogen-consuming Arcobacter, indicating that mutualistic interaction between these two groups of microbes might be pervasive. Our results support the notion that molecular mechanisms involved in virulence can also support mutualism, as shown here for Arcobacter and Breviatea. PMID- 27279224 TI - Universality of human microbial dynamics. AB - Human-associated microbial communities have a crucial role in determining our health and well-being, and this has led to the continuing development of microbiome-based therapies such as faecal microbiota transplantation. These microbial communities are very complex, dynamic and highly personalized ecosystems, exhibiting a high degree of inter-individual variability in both species assemblages and abundance profiles. It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies--the Human Microbiome Project and the Student Microbiome Project--we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies. PMID- 27279225 TI - Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice. AB - Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function. The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways, plus glycans present on the antibody's secretory component. Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA. How IgA responses co develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (3) assess the effects of zygosity, birth mode, and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with faecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. Most of these responses were robust to diet, suggesting that 'intrinsic' properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and to help discover ways of repairing or preventing perturbations in this facet of host immunity. PMID- 27279226 TI - The Brazilian Zika virus strain causes birth defects in experimental models. AB - Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain Barre syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment. PMID- 27279227 TI - Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. AB - Precision medicines exert selective pressure on tumour cells that leads to the preferential growth of resistant subpopulations, necessitating the development of next-generation therapies to treat the evolving cancer. The PIK3CA-AKT-mTOR pathway is one of the most commonly activated pathways in human cancers, which has led to the development of small-molecule inhibitors that target various nodes in the pathway. Among these agents, first-generation mTOR inhibitors (rapalogs) have caused responses in 'N-of-1' cases, and second-generation mTOR kinase inhibitors (TORKi) are currently in clinical trials. Here we sought to delineate the likely resistance mechanisms to existing mTOR inhibitors in human cell lines, as a guide for next-generation therapies. The mechanism of resistance to the TORKi was unusual in that intrinsic kinase activity of mTOR was increased, rather than a direct active-site mutation interfering with drug binding. Indeed, identical drug-resistant mutations have been also identified in drug-naive patients, suggesting that tumours with activating MTOR mutations will be intrinsically resistant to second-generation mTOR inhibitors. We report the development of a new class of mTOR inhibitors that overcomes resistance to existing first- and second-generation inhibitors. The third-generation mTOR inhibitor exploits the unique juxtaposition of two drug-binding pockets to create a bivalent interaction that allows inhibition of these resistant mutants. PMID- 27279228 TI - Ribosome-dependent activation of stringent control. AB - In order to survive, bacteria continually sense, and respond to, environmental fluctuations. Stringent control represents a key bacterial stress response to nutrient starvation that leads to rapid and comprehensive reprogramming of metabolic and transcriptional patterns. In general, transcription of genes for growth and proliferation is downregulated, while those important for survival and virulence are upregulated. Amino acid starvation is sensed by depletion of the aminoacylated tRNA pools, and this results in accumulation of ribosomes stalled with non-aminoacylated (uncharged) tRNA in the ribosomal A site. RelA is recruited to stalled ribosomes and activated to synthesize a hyperphosphorylated guanosine analogue, (p)ppGpp, which acts as a pleiotropic secondary messenger. However, structural information about how RelA recognizes stalled ribosomes and discriminates against aminoacylated tRNAs is missing. Here we present the cryo electron microscopy structure of RelA bound to the bacterial ribosome stalled with uncharged tRNA. The structure reveals that RelA utilizes a distinct binding site compared to the translational factors, with a multi-domain architecture that wraps around a highly distorted A-site tRNA. The TGS (ThrRS, GTPase and SpoT) domain of RelA binds the CCA tail to orient the free 3' hydroxyl group of the terminal adenosine towards a beta-strand, such that an aminoacylated tRNA at this position would be sterically precluded. The structure supports a model in which association of RelA with the ribosome suppresses auto-inhibition to activate synthesis of (p)ppGpp and initiate the stringent response. Since stringent control is responsible for the survival of pathogenic bacteria under stress conditions, and contributes to chronic infections and antibiotic tolerance, RelA represents a good target for the development of novel antibacterial therapeutics. PMID- 27279229 TI - Charge-density analysis of an iron-sulfur protein at an ultra-high resolution of 0.48 A. AB - The fine structures of proteins, such as the positions of hydrogen atoms, distributions of valence electrons and orientations of bound waters, are critical factors for determining the dynamic and chemical properties of proteins. Such information cannot be obtained by conventional protein X-ray analyses at 3.0-1.5 A resolution, in which amino acids are fitted into atomically unresolved electron density maps and refinement calculations are performed under strong restraints. Therefore, we usually supplement the information on hydrogen atoms and valence electrons in proteins with pre-existing common knowledge obtained by chemistry in small molecules. However, even now, computational calculation of such information with quantum chemistry also tends to be difficult, especially for polynuclear metalloproteins. Here we report a charge-density analysis of the high-potential iron-sulfur protein from the thermophilic purple bacterium Thermochromatium tepidum using X-ray data at an ultra-high resolution of 0.48 A. Residual electron densities in the conventional refinement are assigned as valence electrons in the multipolar refinement. Iron 3d and sulfur 3p electron densities of the Fe4S4 cluster are visualized around the atoms. Such information provides the most detailed view of the valence electrons of the metal complex in the protein. The asymmetry of the iron-sulfur cluster and the protein environment suggests the structural basis of charge storing on electron transfer. Our charge-density analysis reveals many fine features around the metal complex for the first time, and will enable further theoretical and experimental studies of metalloproteins. PMID- 27279231 TI - Micro ribonucleic acid-93 promotes oncogenesis of cervical cancer by targeting RAB11 family interacting protein 1. AB - AIM: Micro ribonucleic acid (RNA)-93 (miR-93) is a novel oncogenic miRNA dysregulated in many types of tumors. We aimed to further study the expression pattern and clinical significance of miR-93 and its target, the RAB11 family interacting protein 1 (RAB11FIP1) gene, in cervical cancer. METHODS: Mir-93 and RAB11FIP1 expression in cervical cancer (n = 168), cervical intraepithelial neoplasia (CIN) 2 or 3 (n = 60) and normal cervical tissues (n = 48) was examined by real-time reverse transcription polymerase chain reaction and immunohistochemical staining. Methyl thiazolyl tetrazolium assay, flow cytometry, and Transwell chamber invasion assay were performed to investigate the function of miR-93 in the proliferation, apoptosis and invasion of cervical cancer cell lines SiHa and CaSki. Luciferase activity assay was conducted to identify the target gene of miR-93. RESULTS: Mir-93 expression levels in cervical cancer and CIN tissues were significantly increased (P = 0.032), but the RAB11FIP1 protein was significantly decreased (P = 0.006) compared with normal tissues. Neither was associated with clinicopathological variables. Enforced miR-93 knockdown or RAB11FIP1 overexpression suppressed proliferation and promoted apoptosis, but did not influence invasion in cervical cancer cells. Luciferase activity indicated that RAB11FIP1 was a direct target for miR-93. CONCLUSIONS: Our findings suggest that overexpression of miR-93 via targeting RAB11FIP1 as an early event plays an important role in oncogenesis of cervical cancer. MiR-93 and its target protein RAB11FIP1 may be potential therapeutic targets for cervical cancer and its precursors. PMID- 27279232 TI - Impact of aortocaval shunt flow on cardiac and renal function in unilateral nephrectomized rats. AB - We previously reported significantly enhanced cardiac remodeling post aortocaval fistula (AV) in unilateral nephrectomized (UNX) rats. However, the relationship between the size of the AV and the cardiorenal effects in UNX rats remains unknown. In the present study, AV was induced by 20, 18 and 16 gauge needles in UNX rats to see if larger shunt would definitely induce heavier cardiac and renal damage in UNX rats. Our results demonstrated that bigger shunt size is linked with proportional more significant cardiorenal remodeling and dysfunction in UNX rats. Expression of inflammatory biomarkers including CRP, TNF-alpha, IL-6, IL 1beta, TGF-beta and MCP-1 in left kidney and heart was significantly increased in all UNX + AV groups compared to Sham rats. Inflammation might thus participate in the worsening cardiorenal functions and remodeling processes in this model. PMID- 27279233 TI - Clinical Trials in Non-Small Cell Lung Cancer with Biomarker-Driven Treatment Allocation: Ready or Not, Here We Come. AB - Lung cancer is the leading cause of cancer mortality. Great advances in non-small cell lung cancer therapy have been seen in the last decade, beginning with the success in treating lung cancer harboring EGFR mutations and ALK-gene rearrangements. The potential of these biomarker-driven therapies has propelled research in biomarker targeted approaches to the forefront of lung cancer research. The successful development of immunotherapeutic agents targeting PD-L1 and PD-1 with an associated non-genomic biomarker has opened a new front in the effort for targeted approaches. Although early-phase lung cancer studies have hinted at the potential to use biomarkers to select patients for allocation to treatment in the conduct of clinical trials, data from late-phase studies have tempered expectations. The data leave unclear the wisdom of routinely restricting enrollment on lung cancer clinical trials to biomarker restricted populations, particularly non-genomic biomarkers. PMID- 27279234 TI - Non-Small Cell Lung Cancers in Women and Men: Differences in Biology, Behavior, and Outcomes. AB - Lung cancer is the leading cause of cancer deaths in men and women, both because of its high incidence rates and poor prognosis without effective therapies. Environmental carcinogens, most predominantly tobacco smoke, play a significant role. There are continuously emerging data to suggest the biological process differs between lung cancers in men and women. Differences are seen in a variety of cellular pathways and responses to carcinogens and therapies. Particular note in this article is made of carcinogen processing by cytochrome P450s, estrogen receptor pathways, epidermal growth factor receptor mutations, and how these are not necessarily independent cellular processes. These topics are only very briefly summarized here and it was not possible to include many important references. The heterogeneity of lung cancers in men and women, as well as smokers and nonsmokers, are likely to become more apparent with further studies. Work previously done in our laboratory (EDRN, PIs David Chia & Lee Goodglick) served to further emphasize these differences. This report is dedicated to the memory of Lee Goodglick with whom I had the privilege to work for many years prior to his untimely death. PMID- 27279235 TI - Liquid Biopsies in the Screening of Oncogenic Mutations in NSCLC and its Application in Targeted Therapy. AB - Non-small cell lung cancer (NSCLC) still dominates cancer-related deaths in America. Despite this, new discoveries and advancements in technology are helping with the detection and treatment of NSCLC. The discovery of circulating tumor DNA in blood and other biofluids is essential for the creation of a DNA biomarker. Limitations in technology and sequencing have stunted assay development, but with recent advancements in the next-generation sequencing, droplet digital PCR, and EFIRM, the detection of mutations in biofluids has become possible with reasonable sensitivity and specificity. These methods have been applied to the detection of mutations in NSCLC by measuring the levels of circulating tumor DNA. ALK fusion genes along with mutations in EGFR and KRAS have been shown to correlate to tumor size and metastasis. These methods allow for noninvasive, affordable, and efficient diagnoses of oncogenic mutations that overcome the issues of traditional biopsies. These issues include tumor heterogeneity and early detection of cancers with asymptomatic early stages. Early detection and treatment remain the best way to ensure survival. This review aims to describe these new technologies along with their application in mutation detection in NSCLC in order to proactively utilize targeted anticancer therapy. PMID- 27279236 TI - Estrogen Receptor-beta and the Insulin-Like Growth Factor Axis as Potential Therapeutic Targets for Triple-Negative Breast Cancer. AB - Triple-negative breast cancers (TNBCs) lack estrogen receptor-alpha (ERalpha), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) amplification and account for almost half of all breast cancer deaths. This breast cancer subtype largely affects women who are premenopausal, African American, or have BRCA1/2 mutations. Women with TNBC are plagued with higher rates of distant metastasis that significantly diminish their overall survival and quality of life. Due to their poor response to chemotherapy, patients with TNBC would significantly benefit from development of new targeted therapeutics. Research suggests that the insulin-like growth factor (IGF) family and estrogen receptor beta-1 (ERbeta1), due to their roles in metabolism and cellular regulation, might be attractive targets to pursue for TNBC management. Here, we review the current state of the science addressing the roles of ERbeta1 and the IGF family in TNBC. Further, the potential benefit of metformin treatment in patients with TNBC as well as areas of therapeutic potential in the IGF-ERbeta1 pathway are highlighted. PMID- 27279237 TI - Regulation of FAK Activity by Tetraspan Proteins: Potential Clinical Implications in Cancer. AB - Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that regulates multiple cell signaling pathways in both physiological and pathological conditions. Overexpression and activation of FAK is associated with many advanced stage cancers through promoting cancer cell tumorigenicity and progression as well as by regulating the tumor microenvironment. FAK has multiple binding partners through which FAK exerts its functions including RhoGEF, Src family, talin, cortactin, and paxilin. Over the last few years, it has been proposed that a novel group of four transmembrane proteins can interact with FAK and regulate its activity. These include select tetraspanins such as CD151 and CD9 as well as the GAS3 family members epithelial membrane protein-2 (EMP2) and peripheral myelin protein-22 (PMP22). In this review, we discuss the current knowledge of the interaction between FAK and tetraspan proteins in physiological and pathological conditions, with an emphasis on the potential of tetraspan family members as therapeutic targets in cancer. PMID- 27279238 TI - Extracellular Vesicle-Mediated Reversal of Paclitaxel Resistance in Prostate Cancer. AB - Prostate cancer (PCa) is the most common solid tumor in males and the second leading cause of cancer-related deaths in males in the United States. The current first line therapy for metastatic PCa is androgen deprivation therapy and is initially effective against the disease. However, castrate resistant prostate cancer (CRPC) develops in many men within 18-36 months, rendering this treatment ineffective. Chemotherapy, with a class of drugs known as taxanes is the standard of-care cytotoxic option in metastatic castrate resistant PCa (mCRPC). However, the overall survival advantage for chemotherapy in mCRPC is only 2.2 months and the cancer cells often become resistant to these drugs as well. Once patients fail chemotherapy the progression to death is inevitable. Extracellular vesicles (EVs) are involved in cell signaling and play a role in cancer progression. Previous work has demonstrated that EVs are involved in the development of drug resistance in cancer cells. We report the reversal of taxane resistance and tumorigenic phenotype in PCa cells after EVs treatment. This study suggests that EVs represent a potentially novel therapeutic treatment option for CRPC. PMID- 27279239 TI - Hypoxia-Induced Signaling Promotes Prostate Cancer Progression: Exosomes Role as Messenger of Hypoxic Response in Tumor Microenvironment. AB - Prostate cancer (PCA) is the leading malignancy in men and the second leading cause of cancer-related deaths. Hypoxia (low O2 condition) is considered an early event in prostate carcinogenesis associated with an aggressive phenotype. In fact, clinically, hypoxia and hypoxia-related biomarkers are associated with treatment failure and disease progression. Hypoxia-inducible factor 1 (HIF-1) is the key factor that is activated under hypoxia, and mediates adaptation of cells to hypoxic conditions through regulating the expression of genes associated with angiogenesis, epithelial-to-mesenchymal transition (EMT), metastasis, survival, proliferation, metabolism, sternness, hormone-refractory progression, and therapeutic resistance. Besides HIF-1, several other signaling pathways including PI3K/Akt/mTOR, NADPH oxidase (NOX), Wnt/b-catenin, and Hedgehog are activated in cancer cells under hypoxic conditions, and also contribute in hypoxia-induced biological effects in HIF-1-dependent and -independent manners. Hypoxic cancer cells cause extensive changes in the tumor microenvironment both local and distant, and recent studies have provided ample evidence supporting the crucial role of nanosized vesicles "exosomes" in mediating hypoxia-induced tumor microenvironment remodeling. Exosomes' role has been reported in hypoxia-induced angiogenesis, sternness, activation of cancer-associated fibroblasts (CAFs), and EMT. Together, existing literature suggests that hypoxia plays a predominant role in PCA growth and progression, and PCA could be effectively prevented and treated via targeting hypoxia/hypoxia-related signaling pathways. PMID- 27279241 TI - Drug Development for Metastasis Prevention. AB - Metastatic disease is responsible for 90% of death from solid tumors. However, only a minority of metastasis-specific targets has been exploited therapeutically, and effective prevention and suppression of metastatic disease is still an elusive goal. In this review, we will first summarize the current state of knowledge about the molecular features of the disease, with particular focus on steps and targets potentially amenable to therapeutic intervention. We will then discuss the reasons underlying the paucity of metastatic drugs in the current oncological arsenal and potential ways to overcome this therapeutic gap. We reason that the discovery of novel promising targets, an increased understanding of the molecular features of the disease, the effect of disruptive technologies, and a shift in the current preclinical and clinical settings have the potential to create more successful drug development endeavors. PMID- 27279240 TI - Review of the GAS3 Family of Proteins and their Relevance to Cancer. AB - The GAS3 family of tetraspan proteins has recently been implicated in the progression of cancer. Currently, six members of the GAS3 family have been identified in humans and mice, and while their expressions in disease vary, data suggest that they play a role in epithelial cell structure and function. In this review, we highlight the studies implicating four of the members in disease pathogenesis as well as probe the structural similarities between the family members. Finally, the impact of targeting select members of the family such as PMP22 and EMP2 is discussed. PMID- 27279243 TI - Emerging Receptor Tyrosine Kinase Drug Targets: Implications for Antibody-Based Therapies for Oncology and Immunologic Disorders. AB - Protein kinases play a critical regulatory role in essentially every aspect of cell biology. Of the 518 known kinases, the most successful class for drug targeting is the receptor tyrosine kinase (RTK) family consisting of 58 distinct and diverse members. RTKs regulate a broad range of cellular functions, including proliferation, differentiation, survival, and apoptosis and have been intensively studied in development and cancer. Targeting of RTKs has resulted in many marketed small molecule and antibody-based drugs in a number of different solid tumors and hematological malignancies, and more recently in inflammatory diseases such as idiopathic pulmonary fibrosis. In this review, we discuss some of the RTKs in cancer in which drugs targeting the ErbB family (EGFR, HER2, and ErbB3) and KIT have had meaningful clinical benefit to cancer patients, RTKs' emerging role in regulating innate immunity, and the potential to explore targeting RTKs outside of oncology. PMID- 27279242 TI - Dynamins and BAR Proteins-Safeguards against Cancer. AB - Dynamins and BAR proteins are crucial in a wide variety of cellular processes for their ability to mediate membrane remodeling, such as membrane curvature and membrane fission and fusion. In this review, we highlight dynamins and BAR proteins and the cellular mechanisms that are involved in the initiation and progression of cancer. We specifically discuss the roles of the seproteinsin endocytosis, endo-lysosomal trafficking, autophagy, and apoptosis as these processes are all tightly linked to membrane remodeling and cancer. PMID- 27279244 TI - Journey from Jumping Genes to Gene Therapy. AB - Gene therapy for cancer is a still evolving approach that resulted from a long history of studies into genetic modification of organisms. The fascination with manipulating gene products has spanned hundreds if not thousands of years, beginning with observations of the hereditary nature of traits in plants and culminating to date in the alteration of genetic makeup in humans via modern technology. From early discoveries noting the potential for natural mobility of genetic material to the culmination of clinical trials in a variety of disease, gene transfer has had an eventful and sometimes tumultuous course. Within the present review is a brief history of the biology of gene transfer, how it came to be applied to genetic diseases, and its early applications to cancer therapies. Some of the different types of methods used to modify cells, the theories behind the approaches, and some of the limitations encountered along the way are reviewed. PMID- 27279245 TI - Epigenetic/Genetic Mismatch: Using Transdifferentiation as a Potential Cancer Therapy to Exploit the Cell Type Specificity of Cancer. AB - Every cell type capable of proliferation can be malignantly transformed. However, there appears to be no naturally occurring universal set of genetic mutations capable of converting every cell type to a malignant state. Any specific cell type is generally resistant to transformation by the cancer mutations accumulated by cells of different lineages, presumably due to epigenetic differences. Evidence for this idea derives from experiments in which the developmental fates of cancer cells are altered to reduce malignancy. Reprogramming cancer cells to more primitive developmental states using pluripotency factors (IPS) or somatic nuclear transfer suppresses the malignant phenotype, as does subsequent directed differentiation to mature cells of lineages distinct from the originating cell. Direct transdifferentiation to an alternative cell fate also reduces tumorigenicity. In contrast, after reprogramming, cells induced to redifferentiate toward the original tumor cell type are tumorigenic. In these types of experiments an epigenetic/genetic mismatch often results in suppression of malignancy or cell death. Elucidating the specific transcription and cell signaling network incompatibilities will identify new targets for cancer therapy. Moreover, novel strategies to induce an incompatible transdifferentiated state, in which expression of thousands of genes are altered, will prove useful in controlling malignancies that otherwise easily evolve resistance to single target based therapeutics. Engineering small molecules, genetic vectors, cytokines, growth factors, targeted extracellular vesicles, and cell fusion will help realize transdifferentiation-based therapeutics for cancer. PMID- 27279246 TI - Overexpression of neuromedin U is correlated with regional metastasis of head and neck squamous cell carcinoma. AB - Regional metastasis is an important prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). Neuromedin U (Nmu) is a secreted neuropeptide, named due to its potent uterine contraction-inducing activity. The aim of the present study was to analyze the significance of Nmu in the regional metastasis of HNSCC. The characteristics of 240 patients recruited from the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University (Wuhan, China) were summarized retrospectively. The positive rate of neck dissection was analyzed according to the material. The expression levels of Nmu in human tumor samples were analyzed using immunohistochemistry. Subsequently, the expression of Nmu was investigated using a tissue microassay to analyze the association between Nmu protein expression and Tumor Node Metastasis (TNM) status. The positive rate of neck dissection was 51.4% in the study sample. The expression levels of Nmu in primary tumors with regional metastasis were higher, compared with those without metastasis. There was increased protein expression of Nmu in the advanced tumor tissues. The data obtained in the present study demonstrated that the expression of Nmu was correlated with regional metastasis and TNM status. Overexpression of Nmu may be involved in the process of regional metastasis of HNSCC, and may serve as a novel and valuable biomarker for predicting regional metastasis in patients with HNSCC. PMID- 27279248 TI - A single session of neuromuscular electrical stimulation does not augment postprandial muscle protein accretion. AB - The loss of muscle mass and strength that occurs with aging, termed sarcopenia, has been (at least partly) attributed to an impaired muscle protein synthetic response to food intake. Previously, we showed that neuromuscular electrical stimulation (NMES) can stimulate fasting muscle protein synthesis rates and prevent muscle atrophy during disuse. We hypothesized that NMES prior to protein ingestion would increase postprandial muscle protein accretion. Eighteen healthy elderly (69 +/- 1 yr) males participated in this study. After a 70-min unilateral NMES protocol was performed, subjects ingested 20 g of intrinsically l-[1 (13)C]phenylalanine-labeled casein. Plasma samples and muscle biopsies were collected to assess postprandial mixed muscle and myofibrillar protein accretion as well as associated myocellular signaling during a 4-h postprandial period in both the control (CON) and stimulated (NMES) leg. Protein ingestion resulted in rapid increases in both plasma phenylalanine concentrations and l-[1 (13)C]phenylalanine enrichments, which remained elevated during the entire 4-h postprandial period (P < 0.05). Mixed-muscle protein-bound l-[1 (13)C]phenylalanine enrichments increased significantly over time following protein ingestion, with no differences between the CON (0.0164 +/- 0.0019 MPE) and NMES (0.0164 +/- 0.0019 MPE) leg (P > 0.05). In agreement, no differences were observed in the postprandial rise in myofibrillar protein bound l-[1 (13)C]phenylalanine enrichments between the CON and NMES legs (0.0115 +/- 0.0014 vs. 0.0133 +/- 0.0013 MPE, respectively, P > 0.05). Significant increases in mTOR and P70S6K phosphorylation status were observed in the NMES-stimulated leg only (P < 0.05). We conclude that a single session of NMES prior to food intake does not augment postprandial muscle protein accretion in healthy older men. PMID- 27279247 TI - Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans. AB - Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P <= 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient initiated signal in the jejunum that regulates ghrelin secretion. PMID- 27279249 TI - Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1. AB - Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n = 7) compared with lean (LN; n = 10) female Sprague Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P < 0.001), greater fat mass (P < 0.001), and reduced lean mass (P < 0.05) and developed metabolic dysfunction with elevated serum lipids, insulin, leptin, and CCL2 (P < 0.05) compared with LN dams. Microarray analyses identified 284 differentially expressed genes between ovaries from LN vs. OB dams (+/-1.3 fold, P < 0.05). RT qPCR confirmed a decrease in expression of glucose transporters GLUT4 and GLUT9 and elevation of proinflammatory genes, including CCL2, CXCL10, CXCL11, CCR2, CXCR1, and TNFalpha in ovaries from OB compared with LN (P < 0.05). Protein levels of PI3K and phosphorylated Akt were significantly decreased (P < 0.05), whereas nuclear levels of Egr-1 (P < 0.05) were increased in OB compared with LN ovaries. Moreover, Egr-1 was localized to granulosa cells, with the highest expression in cumulus cells of preovulatory follicles. mRNA expression of VCAN, AURKB, and PLAT (P < 0.05) correlated with %visceral fat weight (r = 0.51, -0.77, and -0.57, respectively, P <= 0.05), suggesting alterations in ovarian function with obesity. In summary, maternal obesity led to an upregulation of inflammatory genes and Egr-1 expression in peri-implantation ovarian tissue and a concurrent downregulation of GLUTs and Akt and PI3K protein levels. PMID- 27279250 TI - Identifying the independent effect of HbA1c variability on adverse health outcomes in patients with Type 2 diabetes. AB - AIMS: To characterize the relationship between HbA1c variability and adverse health outcomes among US military veterans with Type 2 diabetes. METHODS: This retrospective cohort study used Veterans Affairs and Medicare claims for veterans with Type 2 diabetes taking metformin who initiated a second diabetes medication (n = 50 861). The main exposure of interest was HbA1c variability during a 3-year baseline period. HbA1c variability, categorized into quartiles, was defined as standard deviation, coefficient of variation and adjusted standard deviation, which accounted for the number and mean number of days between HbA1c tests. Cox proportional hazard models predicted mortality, hospitalization for ambulatory care-sensitive conditions, and myocardial infarction or stroke and were controlled for mean HbA1c levels and the direction of change in HbA1c levels during the baseline period. RESULTS: Over a mean 3.3 years of follow-up, all HbA1c variability measures significantly predicted each outcome. Using the adjusted standard deviation measure for HbA1c variability, the hazard ratios for the third and fourth quartile predicting mortality were 1.14 (95% CI 1.04, 1.25) and 1.42 (95% CI 1.28, 1.58), for myocardial infarction and stroke they were 1.25 (95% CI 1.10, 1.41) and 1.23 (95% CI 1.07, 1.42) and for ambulatory-care sensitive condition hospitalization they were 1.10 (95% CI 1.03, 1.18) and 1.11 (95% CI 1.03, 1.20). Higher baseline HbA1c levels independently predicted the likelihood of each outcome. CONCLUSIONS: In veterans with Type 2 diabetes, greater HbA1c variability was associated with an increased risk of adverse long term outcomes, independently of HbA1c levels and direction of change. Limiting HbA1c fluctuations over time may reduce complications. PMID- 27279251 TI - beta-Blockers and Vascular Hemodynamics in Patients With Peripheral Arterial Disease. AB - Aortic augmentation index (AIx) is a marker of central aortic pressure burden and is modulated by antihypertensive drugs. In patients with peripheral arterial disease (PAD) undergoing antihypertensive treatment, aortic pressures parameters, heart rate-adjusted augmentation index (AIx75), and unadjusted AIx were determined. The (aortic) systolic and diastolic blood pressure did not differ between PAD patients who were taking beta-blockers (n=61) and those who were not taking beta-blockers (n=80). In patients taking beta-blockers, augmentation pressure and pulse pressure were higher than in patients who did not take beta blockers (augmentation pressure, P=.02; pulse pressure, P=.005). AIx75 was lower in PAD patients taking beta-blockers than in patients not taking beta-blockers (P=.04), while the AIx did not differ between PAD patients taking and not taking beta-blockers. The present study demonstrates that beta-blockers potentially affect markers of vascular hemodynamics in patients with PAD. Because these markers are surrogates of cardiovascular risk, further studies are warranted to clarify the impact of selective beta-blocker treatment on clinical outcome in patients with PAD. PMID- 27279253 TI - John Corbett McDonald. PMID- 27279254 TI - Gender and Conflict Resolution Strategies in Spanish Teen Couples: Their Relationship With Jealousy and Emotional Dependency. AB - Previous research has pointed to the need to address the study of violence in teen couples. However, research has not delved into the study of the variables related to the different types of violence employed by boys and girls. The purpose of this study was to test whether gender, jealousy, and dependency predict specific strategies for conflict resolution (psychological aggression and mild physical aggression). Another objective of the study was to test gender differences in the conflict resolution strategies used by Spanish teen couples and to test the association between these variables and jealousy and emotional dependency. A sample of 296 adolescent high school students between 14 and 19 years of age of both genders from the south of Spain participated in this study. Hierarchical regression models were used to estimate the relationship between psychological aggression and mild physical aggression, and jealousy, and dependency. Results showed that jealousy correlated with psychological aggression and mild physical aggression in girls but not in boys. Psychological aggression and mild physical aggression were associated with dependency in boys. Girls scored higher in psychological aggression and jealousy than did boys. Finally, the interaction between jealousy and dependency predicted psychological aggression only in girls. These results highlight the need to address the role of the interaction between dependence and jealousy in the types of violence employed in teen dating. However, it is necessary to delve into the gender differences and similarities to develop appropriate prevention programs. PMID- 27279255 TI - Pre- and Postnatal Effects of Corticosterone on Fitness-Related Traits and the Timing of Endogenous Corticosterone Production in a Songbird. AB - Maternally derived corticosterone in the egg and corticosterone produced endogenously by altricial nestling birds play essential roles during development. Although persistently high corticosterone levels can be harmful, moderately elevated levels above baseline can lead to reallocation of resources between growth and maintenance to ensure immediate survival or to enhance the development of fitness-related traits. We tested two hypotheses concerning the fitness consequences of elevated corticosterone during prenatal and postnatal development in altricial house wrens: (1) elevated corticosterone shifts resources away from growth and immune function and (2) elevated corticosterone serves as a signal to allocate resources to fitness-related traits. We also explored the development of the stress response, hypothesizing that early-stage nestlings have little endogenously produced corticosterone, but that their baseline and stress-induced corticosterone levels increase with age. Nestlings hatching from corticosterone injected eggs were lighter at hatching, but through compensatory growth, ended up heavier than controls near the time of fledging, an important, fitness-related trait. Nestlings that hatched from corticosterone-injected eggs and those given oral doses of corticosterone did not differ from controls in three other fitness related traits: immunoresponsiveness, size, or haematocrit. Early- and late-stage nestlings had similar baseline corticosterone levels, and all nestlings increased their plasma corticosterone levels in response to a capture-and-restraint protocol, with older nestlings mounting a stronger stress-induced response than younger nestlings. These results suggest that prenatal exposure to corticosterone is important in shaping offspring phenotype and are consistent with the hypothesis that maternally derived corticosterone in the egg can have long-term, fitness-related effects on offspring phenotype. PMID- 27279257 TI - Increased intramuscular fat induced by reduced dietary protein in finishing pigs: effects on the longissimus lumborum muscle proteome. AB - Due to genetic selection towards reduced subcutaneous fat, the amount of intramuscular fat (IMF) in commercial pigs has been reduced (<2.5%), compromising pork quality. The use of reduced protein diets (RPD) is a good strategy to increase IMF in pigs. We have previously shown that increased IMF promoted by RPD is mediated by lysine restriction. However, the molecular mechanisms involved remain unclear. Here we performed a proteomics study to quantify differentially regulated proteins in the longissimus lumborum muscle of pigs (n = 4) fed a normal protein diet (NPD) (16.0% CP) or a reduced protein diet (RPD) (13.0% CP). Both isobaric tags for relative and absolute quantification (iTRAQ) and label free methods were used. Glycolysis, Krebs cycle, mitochondrion, contractile proteins, respiratory chain, and calcium signalling were significantly enriched in muscle samples. Thirty five proteins shown to be differentially expressed and were classified using gene ontology (GO) terms and functional annotation clustering, highlighting main relevant biological networks and proteins associated with muscle physiology and meat quality. Members of GO categories "muscle contraction" and "structural constituents of cytoskeleton", were the most significantly up-regulated proteins in muscle from pigs fed RPD. Conversely, in animals fed NPD most up-regulated proteins were enzymes involved in the regulation of energy metabolism. Our data revealed that RPD affects the amounts of proteins related to fibre type and structure, and energy metabolism. It is suggested that the increased IMF promoted by dietary protein reduction in growing finishing pigs is mediated by shifting the metabolic properties of fibres from glycolytic to oxidative. PMID- 27279258 TI - Experimental evidence of incomplete fluorescence quenching of pyrene bound to humic substances: implications for Koc measurements. AB - Fluorescence quenching (FQ) is extensively used for quantitative assessment of partition coefficients (KOC) of polycyclic aromatic hydrocarbons (PAHs) to natural organic materials - humic substances (HS). The presence of bound PAHs with incompletely quenched fluorescence would lead to underestimation of the KOC values measured by this technique. The goal of this work was to prove the validity of this assumption using an original experimental setup, which implied FQ measurements upon excitation into two distinct vibronically coupled electronic states. Pyrene was used as a fluorescent probe, and aquatic fulvic acid (SRFA) and leonardite humic acid (CHP) were used as the humic materials with low and high binding affinity for pyrene, respectively. Excitation of pyrene into the forbidden (S0-S1) and allowed (S0-S2) electronic states yielded two pairs of nonidentical FQ curves. This was indicative of incomplete quenching of the bound pyrene, and the divergence of the two FQ curves was much more pronounced for CHP as compared to SRFA. The two component model of fluorescence response formation was proposed to estimate the KOC values from the data obtained. The resulting pyrene KOC value for CHP (220 +/- 20) g L(-1) was a factor 3 higher compared to the KOC value determined with the use of the Stern-Volmer formalism (68 +/- 2) g L(-1). At the same time for aquatic FA the difference in FQ curves was almost negligible, which enables the use of the Stern-Volmer formalism for weakly interacting HS and PAHs. PMID- 27279256 TI - Combination treatment with flavonoid morin and telomerase inhibitor MST-312 reduces cancer stem cell traits by targeting STAT3 and telomerase. AB - Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. The malignant CRC that undergoes metastasis in the advanced stage is usually refractory to existing chemotherapy and shows a poor prognosis. However, to date, efficient targeted-therapy for metastatic CRC is ill-defined. We tested the hypothesis that combined treatment of flavonoid morin and telomerase inhibitor MST-312 may reduce the cancer stem cell (CSC) traits. To characterize CSC phenotype, we performed the CD133/CD44 subpopulation profiling, tumorsphere formation assay, cell invasion assay and wound healing assay. We have examined the augmenting effects of the combined treatment of morin and MST-312 for 5-FU (5 fluorouracil) efficacy in human colorectal cancer. Morin and MST-312 combined treatment reduced CD133 (+) and CD44 (+) subpopulations in human colorectal and breast cancer cells, respectively. Tumorsphere formation and cell invasiveness were decreased with the morin and MST-312 combination treatment. Consistent with these data, morin and MST-312 treatment decreased the wound healing capacity of human breast cancer cells. Stress and apoptosis antibody arrays revealed that there were specific upregulated and downregulated proteins resulting from different treatments. Phosphorylation levels of BAD, p53 and Chk1 were enhanced upon morin/MST-312 treatments in HT-29 cells, whereas caspase-3 cleavage level and expression of IkappaBalpha were downregulated by combined morin/MST-312 treatment in SW620 cells. Finally, morin and MST-312 co-treatment further augmented the 5-FU efficacy, chemosensitizing the 5-FU resistant human colorectal cancer cells. Taken together, our study suggests that novel targeted-therapy can be implemented by using flavonoid morin and telomerase inhibitor MST-312 for improved cancer prognosis. PMID- 27279259 TI - Echinococcus multilocularis and other zoonotic parasites in red foxes in Estonia. AB - Red fox (Vulpes vulpes) is the most widely distributed canid in the world and an important source of multiple zoonotic pathogens capable of causing life threatening diseases, such as rabies and alveolar echinococcosis. Informing general public of potential risks related to foxes is becoming more important since the fox densities have increased in many countries and the species is colonizing urban areas in Europe and around the world with increasing pace, bringing zoonotic pathogens to the immediate neighbourhood of humans and their companion animals. The aim of this study was to examine the parasite fauna of red foxes in Estonia. We found in Estonian foxes a total of 17 endoparasite taxa, including ten zoonotic species. All the analysed individuals were infected and the average parasite species richness was 6.37. However, the infection rates varied to a very large extent for different parasite species, ranging from 0.9 to 91.5%. Of zoonotic species, the highest infection rate was observed for Alaria alata (90.7%), Eucoleus aerophilus (87.6%) and Uncinaria stenocephala (84.3%). The prevalence of tapeworm Echinococcus multilocularis, a causative agent for alveolar echinococcosis, was also relatively high (31.5%), presenting a potential risk to human health. PMID- 27279260 TI - Priming for destruction: septins at the crossroads of mitochondrial fission and bacterial autophagy. PMID- 27279261 TI - The SSV Evaluation System: A Tool to Prioritize Short Structural Variants for Studies of Possible Regulatory and Causal Variants. AB - Short structural variants (SSVs) are short genomic variants (<50 bp) other than SNPs. It has been suggested that SSVs contribute to many human complex traits. However, high-throughput analysis of SSVs presents numerous technical challenges. In order to facilitate the discovery and assessment of SSVs, we have developed a prototype bioinformatics tool, "SSV evaluation system," which is a searchable, annotated database of SSVs in the human genome, with associated customizable scoring software that is used to evaluate and prioritize SSVs that are most likely to have significant biological effects and impact on disease risk. This new bioinformatics tool is a component in a larger strategy that we have been using to discover potentially important SSVs within candidate genomic regions that have been identified in genome-wide association studies, with the goal to prioritize potential functional/causal SSVs and focus the follow-up experiments on a relatively small list of strong candidate SSVs. We describe our strategy and discuss how we have used the SSV evaluation system to discover candidate causal variants related to complex neurodegenerative diseases. We present the SSV evaluation system as a powerful tool to guide genetic investigations aiming to uncover SSVs that underlie human complex diseases including neurodegenerative diseases in aging. PMID- 27279262 TI - Novel Approach to the Detection of Left Ventricular Hypertrophy Using Body Mass Index-Corrected Electrocardiographic Voltage Criteria in a Group of African Ancestry. AB - BACKGROUND: Electrocardiographic (ECG) QRS voltages used to generate criteria for left ventricular hypertrophy (LVH) detection are considerably attenuated by obesity. This effect renders the utility of ECG criteria to detect LVH in obese individuals of African ancestry to be of limited value. HYPOTHESIS: A novel approach to correcting QRS voltages for the attenuating effect of body mass index (BMI) will improve the ability of ECG criteria to detect LVH in a group of African descent. METHODS: Left ventricular mass was determined from echocardiography in 661 randomly selected participants (43.0% obese) of black African ancestry in South Africa. RESULTS: As compared with Cornell and Sokolow Lyon voltage criteria, BMI best correlated with RaVL , Gubner-Ungerleider, and Lewis QRS complex voltages, but these relations were noted only in those with BMI <29 kg/m(2) . Correcting RaVL and Lewis voltages by the difference in the slope of BMI-voltage relations in those with BMI <29 kg/m(2) vs those with BMI >=29 kg/m(2) showed the greatest performance for LVH detection (uncorrected RaVL : 0.695 +/- 0.025, corrected RaVL : 0.733 +/- 0.022; P < 0.0001), and also increased the sensitivity (uncorrected RaVL : 30.6%, corrected RaVL : 42.4%; P < 0.0005) with no significant change in specificity (uncorrected RaVL : 86.3%, corrected RaVL : 83.0%; P = 0.28). CONCLUSIONS: We offer a novel approach to correcting ECG voltages for the attenuating effects of obesity in individuals of African ancestry, and this improves the performance and sensitivity for LVH detection. PMID- 27279263 TI - Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle. AB - BACKGROUND: Cholesterol deficiency (CD), a newly identified autosomal recessive genetic defect in Holstein cattle, is associated with clinical signs of diarrhea, failure to thrive, and hypocholesterolemia. HYPOTHESIS/OBJECTIVES: The objective is to describe the clinicopathological phenotype of affected Holstein cattle homozygous for the causative apolipoprotein B gene (APOB) mutation. ANIMALS: Six Holstein cattle, 5 calves with a clinical history of chronic diarrhea, and 1 heifer with erosions in the buccal cavity and neurologic symptoms were admitted to the Clinic for Ruminants. METHODS: This case review included a full clinical examination, a complete blood count, blood chemistry, and measurements of cholesterol and triglycerides. The animals were euthanized and necropsied. A PCR based direct gene test was applied to determine the APOB genotype. RESULTS: All 6 animals were inbred, could be traced back to the sire Maughlin Storm, and were confirmed homozygous for the APOB mutation. The clinical phenotype included poor development, underweight, and intermittent diarrhea in the calves, and neurologic signs in the heifer included hypermetria and pacing. Hypocholesterolemia and low triglycerides concentrations were present in all animals. The pathological phenotype of all animals was steatorrhea with enterocytes of the small intestine containing intracytoplasmic lipid vacuoles. The peripheral nervous system of the heifer displayed degenerative changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Suspicion of CD in Holstein cattle is based on the presence of chronic diarrhea with no evidence of primary infections. Confirmation of the associated APOB gene mutation is needed. Additionally, the heifer demonstrated primarily signs of neurologic disease providing an unexpected phenotype of CD. PMID- 27279264 TI - Peri-implant crevicular fluid biomarkers as discriminants of peri-implant health and disease. AB - AIM: The objective of this cross-sectional study was to examine the potential of peri-implant crevicular fluid (PICF) analytes to discriminate between peri implant health and disease using a multi-biomarker approach. METHODS: We collected PICF samples from the mesio-buccal site of every implant (n = 145) from 52 subjects with peri-implantitis and measured the levels of 20 biomarkers using Luminex. We grouped implants and subjects based on the clinical characteristic of the sampled sites and implants into: healthy sites from healthy implants (HH), diseased sites from diseased implants (DD) and healthy sites from diseased implants (HD). The significance of the differences between the HH and DD groups was determined using general linear models controlling for false discovery rate. We used logistic regression to determine the best multi-biomarker models that could distinguish HH from DD subjects and HH from HD subjects. RESULTS: There were statistically significant differences between HH and DD groups for 12/20 biomarkers. Logistic regression resulted in a 6-biomarker model (Flt-3L, GM-CSF, IL-10, sCD40L, IL-17 and TNFalpha) that discriminated HH from DD subjects (AUC = 0.93) and a 3-biomarker model (IL-17, IL-1ra and vascular endothelial growth factor) that distinguished HH from DD subjects (AUC = 0.90). CONCLUSION: PICF biomarkers might help discriminate peri-implant health from disease. PMID- 27279265 TI - Ambiphilic boron in 1,4,2,5-diazadiborinine. AB - Boranes have long been known as the archetypal Lewis acids owing to an empty p orbital on the boron centre. Meanwhile, Lewis basic tricoordinate boranes have been developed in recent years. Here we report the synthesis of an annulated 1,4,2,5-diazadiborinine derivative featuring boron atoms that exhibit both Lewis acidic and basic properties. Experimental and computational studies confirmed that two boron atoms in this molecule are spectroscopically equivalent. Nevertheless, this molecule cleaves C-O, B-H, Si-H and P-H bonds heterolytically, and readily undergoes [4+2] cycloaddition reaction with non-activated unsaturated bonds such as C=O, C=C, C=C and C=N bonds. The result, thus, indicates that the indistinguishable boron atoms in 1,4,2,5-diazadiborinine act as both nucleophilic and electrophilic centres, demonstrating ambiphilic nature. PMID- 27279266 TI - Continuous glucose monitoring in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonist dulaglutide in combination with prandial insulin lispro: an AWARD-4 substudy. AB - AIM: To conduct a substudy, using 24-hour continuous glucose monitoring (CGM), of the AWARD-4 trial, which was designed to compare insulin + glucagon-like peptide 1 receptor agonist treatment with an insulin-only regimen. METHODS: The AWARD-4 trial randomized 884 conventional insulin regimen-treated patients to dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, all in combination with prandial insulin lispro. The CGM substudy included 144 patients inserted with a Medtronic CGMS iPro CGM device to enable 3-day glucose monitoring. CGM sessions were completed at weeks 0, 13, 26 and 52. CGM measures included mean 24-hour glucose, percentage time in target glucose ranges, hyper- and hypoglycaemia and glucose variability. The primary objective was treatment comparison for percentage time spent with CGM glucose values in the 3.9-7.8 mmol/L range after 26 weeks. RESULTS: At week 26, mean CGM values decreased in all treatment groups (change from baseline -2.8 +/- 0.3, -2.4 +/- 0.3 and -2.5 +/- 0.3 mmol/L for dulaglutide 1.5 mg, dulaglutide 0.75 mg and glargine, respectively); between-group differences were not statistically significant. Treatment groups were similar for percentage time in the 3.9-7.8 mmol/L range. Percentage time in the 3.9-10.0 mmol/L range was greater for dulaglutide 1.5 mg than for glargine (p < 0.05). Dulaglutide and glargine were associated with decreased glucose variability for all CGM variability indices. The overall within-patient standard deviation (s.d.) was significantly reduced with dulaglutide 1.5 mg versus glargine (p < 0.05). At week 52, there were no significant differences among the groups with regard to measures of normoglycaemia or near-normoglycaemia and for the overall within patient s.d. Treatment with glargine was associated with greater increases in percentage time spent with glucose values <=3.9 mmol/L, with statistically significant differences between the groups at 52 weeks (p < 0.05). CONCLUSIONS: In combination with prandial lispro, treatment with dulaglutide and glargine resulted in similar proportions of glucose values in the normoglycaemic range, but dulaglutide provided an improved balance between the proportion of values within the near-normoglycaemia range and values within the hypoglycaemic range. PMID- 27279267 TI - CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1. AB - Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin dependent kinase inhibitor 1B (p27Kip1) is a cyclin-dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments. PMID- 27279268 TI - Radiation exposure in patients treated with endovascular aneurysm repair: what is the risk of cancer, and can we justify treating younger patients? AB - Background Endovascular aneurysm repair (EVAR) is becoming the mainstay treatment of abdominal aortic aneurisms (AAA). The postoperative follow-up regime includes a lifelong series of CT angiograms (CTAs) at different intervals in addition to EVAR, which will confer significant cumulative radiation exposure over time. Purpose To examine the impact of age and follow-up regime over time on cumulative radiation exposure and attributable cancer risk after EVAR. Material and Methods We calculated a mean effective dose (ED) for the EVAR procedure, CTA, and plain abdominal X-rays (PAX). Cumulative ED was calculated for standard, complex, and simplified surveillance over 5, 10, and 15 years for different age groups. Results For EVAR, the mean ED was 34 mSv (range, 12-75 mSv) per procedure. For PAX, the ED was 1.1 mSv (range, 0.3-4.4 mSv), and for CTA it was 8.0 mSv (range, 2-20 mSv). For a 55-year-old man, an attributable cancer risk (ACR) in standard surveillance at 5 and 15 years of follow-up was 0.35% and 0.65%, respectively. The corresponding values were 0.22% and 0.37% for a 75-year-old man. When using a simplified follow-up, the ACRs for a 55-year-old at 5 and 15 years were 0.30% and 0.37%, respectively. These values were 0.18% and 0.21% for a 75-year-old man. A complex follow-up with half-yearly CTA over similar age and time span doubled the ACR. Conclusion Treating younger patients with EVAR poses a low ACR of 0.65% (15 year standard surveillance) compared to a lifetime cancer risk of 44%. A simplified surveillance should be used if treating younger patients, which will halve the ACR over 15 years. PMID- 27279269 TI - Leminorella sepsis in very low birth weight neonate as cause of neonatal mortality. AB - Leminorella is a member of Enterobacteriaceae family and was known previously as Enteric Group 57. Based upon genetic differences using DNA hybridization, it has three taxa: Leminorella grimontii, Leminorella richardii, and Leminorella sp. strain 3. The third one is similar biochemically to the L. grimontii strains. The generic name has been derived on the name of a French microbiologist, Leon Le Minor. The biochemical properties includes being facultative anaerobes, growth on sheep blood, TSI, and MacConkey agar; hydrogen sulfide producer, l-arabinose fermenter, and tyrosine hydrolyzer; and are negative for d-mannose fermentation, urea, and lipase. They usually infect in adulthood and result in urinary tract infection, surgical site infection, bacteremia, peritonitis, respiratory tract infection, and soft tissue infection. We report the first case of L. grimontii sepsis in a very low birth weight neonate that died because of neonatal sepsis. PMID- 27279270 TI - Columnar cell variant of papillary thyroid carcinoma: A diagnostic dilemma in fine-needle aspiration cytology. AB - Columnar cell variant of papillary thyroid carcinoma (PTC) is an uncommon variant with an aggressive course as compared to classic papillary carcinoma. Cytologic diagnosis of these tumors is difficult due to absence of characteristic nuclear features of classic pattern of papillary carcinoma. We present a case of columnar cell variant in a young female misdiagnosed on aspiration cytology. A 21-year-old female presented with solitary nodule in the left aspect of thyroid. A diagnosis of medullary thyroid carcinoma was rendered. The resected thyoroidectomy specimen revealed a columnar cell variant of PTC which was further supported by immunohistochemical staining. Diagn. Cytopathol. 2016;44:816-819. (c) 2016 Wiley Periodicals, Inc. PMID- 27279271 TI - Assessing covalency in equatorial U-N bonds: density based measures of bonding in BTP and isoamethyrin complexes of uranyl. AB - Calculations performed at the density functional level of theory have been used to investigate complexes of uranyl with the expanded porphyrin isoamethyrin and the bis-triazinyl-pyridine (BTP) ligands, the latter of which is well-known to be effective in the separation of trivalent lanthanides and actinides. Analysis has been performed using a range of density-based techniques, including the Quantum Theory of Atoms in Molecules (QTAIM), the Electron Localisation Function (ELF) and the reduced density gradient (RDG). The effects of peripheral alkyl substituents on UO2-isoamethyrin, known to be vital for proper replication of the experimental geometry, are considered. Evidence for comparable amounts of covalent character has been found in the largely ionic U-N bonds of UO2 isoamethyrin and [UO2(BTP)2](2+) and examination of the variation in the electronic characteristics of the uranyl unit upon complexation in both of these cases reveal striking similarities in the nature of the U-N bonding and the effect of this bonding on the U-Oyl interaction, as well as evidence of donation into the U-N bonding region from the uranyl unit itself. PMID- 27279273 TI - Clustering of cardiovascular behavioral risk factors and blood pressure among people diagnosed with hypertension: a nationally representative survey in China. AB - This study aimed to examine association between the number of behavioral risk factors and blood pressure (BP) level among a nationally representative sample of Chinese people diagnosed with hypertension. A total of 31,694 respondents aged 18+ years with diagnosed hypertension were extracted from the 2013-2014 China Chronic Disease and Risk Factor Surveillance. BP of each respondent was classified into six levels according to criteria in 2007 Guidelines for the Management of Arterial Hypertension. Information for smoking, alcohol drinking, fruit and vegetables consumption, physical inactivity, and overweight and obesity were obtained. The average number of risk factors was determined by BP level to explore potential risk factor clustering. Ten generalized proportional odds models were used to examine association between clustering of behavioral risk factors and BP level. A clear gradient between the number of behavioral risk factors and BP level was observed for men and women (P < 0.05 for both genders). BP level for men and women was much likely to upgrade as number of risk factors accumulated (P < 0.01 for 10 models). Behavioral modifications may decrease BP, and combinations of two or more behavioral interventions could potentially result in even better BP management among people diagnosed with hypertension. PMID- 27279272 TI - Immunobiotic Lactobacillus strains reduce small intestinal injury induced by intraepithelial lymphocytes after Toll-like receptor 3 activation. AB - OBJECTIVE: Intestinal intraepithelial lymphocytes (IELs) play critical roles in disrupting epithelial homeostasis after Toll-like receptor (TLR)-3 activation with genomic rotavirus dsRNA or the synthetic dsRNA analog poly(I:C). The capacity of immunobiotic Lactobacillus rhamnosus CRL1505 (Lr1505) or Lactobacillus plantarum CRL1506 (Lp1506) to beneficially modulate IELs response after TLR3 activation was investigated in vivo using a mice model. RESULTS: Intraperitoneal administration of poly(I:C) induced inflammatory-mediated intestinal tissue damage through the increase of inflammatory cells (CD3(+)NK1.1(+), CD3(+)CD8alphaalpha(+), CD8alphaalpha(+)NKG2D(+)) and pro inflammatory mediators (TNF-alpha, IL-1beta, IFN-gamma, IL-15, RAE1, IL-8). Increased expression of intestinal TLR3, MDA5, and RIG-I was also observed after poly(I:C) challenge. Treatment with Lr1505 or Lp1506 prior to TLR3 activation significantly reduced the levels of TNF-alpha, IL-15, RAE1, and increased serum and intestinal IL-10. Moreover, CD3(+)NK1.1(+), CD3(+)CD8alphaalpha(+), and CD8alphaalpha(+)NKG2D(+) cells were lower in lactobacilli-treated mice when compared to controls. The immunomodulatory capacities of lactobacilli allowed a significant reduction of intestinal tissue damage. CONCLUSIONS: This work demonstrates the reduction of TLR3-mediated intestinal tissue injury by immunobiotic lactobacilli through the modulation of intraepithelial lymphocytes response. It is a step forward in the understanding of the cellular mechanisms involved in the antiviral capabilities of immunobiotic strains. PMID- 27279274 TI - Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: A double-blind randomized controlled trial. AB - SCOPE: To investigate the effects of n-3 fatty acid supplements, both marine and plant-based, on glycemic traits in Chinese type 2 diabetes patients. METHOD AND RESULTS: In a double-blind randomized controlled trial, 185 recruited Chinese type 2 diabetes patients were randomized to either fish oil (FO, n = 63), flaxseed oil (FSO, n = 61), or corn oil group (served as control group, n = 61) for 180 days. The patients were asked to take corresponding oil capsules (four capsules/day), which totally provided 2 g/day of eicosapentaenoic acid + docosahexaenoic acid in FO group and 2.5 g/day of alpha-linolenic acid in FSO group. No group * time interaction was observed for homeostatic model assessment of insulin resistance, fasting insulin, or glucose. Significant group * time interaction (P = 0.035) was observed for glycated hemoglobin A1c (HbA1c), with HbA1c decreased in FO group compared with corn oil group (P = 0.037). We also found significant group * time interactions for lipid traits, including LDL cholesterol (P = 0.043), total cholesterol (P = 0.021), total cholesterol/HDL cholesterol (P = 0.009), and triacylglycerol (P = 0.003), with the lipid profiles improved in FO group. No significant effects of FSO on glycemic traits or blood lipids were observed. CONCLUSIONS: Marine n-3 PUFA supplements may improve glycemic control and lipid profiles among Chinese type 2 diabetic patients. PMID- 27279275 TI - Ag85A/ESAT-6 chimeric DNA vaccine induces an adverse response in tuberculosis infected mice. AB - The Mycobacterium tuberculosis (M. tb) antigens encoded by the 6 kDa early secretory antigenic target (esat-6) and antigen 85A (ag85a) genes are known to exert protective effects against tuberculosis in animal models. In addition, these antigens represent vaccine components that were tested in early human clinical trials. In the present study, a chimeric DNA vaccine was constructed that contained two copies of the esat-6 gene inserted into the ag85a gene from M. tb. BALB/c mice were treated with this chimeric vaccine following infection with either M. tb H37Rv or a clinical multi-drug-resistant tuberculosis isolate. Treatment of both groups of mice with the chimeric vaccine resulted in accelerated mortality. These findings are in contrast with previous results, which indicated that DNA vaccines expressing the individual antigens were either beneficial or at least not harmful. The results of the present study suggested that the ESAT-6 antigen is not suitable for inclusion in therapeutic vaccines. PMID- 27279276 TI - Genotypic variation in spike fertility traits and ovary size as determinants of floret and grain survival rate in wheat. AB - Spike fertility traits are critical attributes for grain yield in wheat (Triticum aestivum L.). Here, we examine the genotypic variation in three important traits: maximum number of floret primordia, number of fertile florets, and number of grains. We determine their relationship in determining spike fertility in 30 genotypes grown under two contrasting conditions: field and greenhouse. The maximum number of floret primordia per spikelet (MFS), fertile florets per spikelet (FFS), and number of grains per spikelet (GS) not only exhibited large genotypic variation in both growth conditions and across all spikelet positions studied, but also displayed moderate levels of heritability. FFS was closely associated with floret survival and only weakly related to MFS. We also found that the post-anthesis process of grain set/abortion was important in determining genotypic variation in GS; an increase in GS was mainly associated with improved grain survival. Ovary size at anthesis was associated with both floret survival (pre-anthesis) and grain survival (post-anthesis), and was thus believed to 'connect' the two traits. In this work, proximal florets (i.e. the first three florets from the base of a spikelet: F1, F2, and F3) produced fertile florets and set grains in most cases. The ovary size of more distal florets (F4 and beyond) seemed to act as a decisive factor for grain setting and effectively reflected pre-anthesis floret development. In both growth conditions, GS positively correlated with ovary size of florets in the distal position (F4), suggesting that assimilates allocated to distal florets may play a critical role in regulating grain set. PMID- 27279277 TI - Phytoplasma SAP11 alters 3-isobutyl-2-methoxypyrazine biosynthesis in Nicotiana benthamiana by suppressing NbOMT1. AB - Phytoplasmas are bacterial phytopathogens that release virulence effectors into sieve cells and act systemically to affect the physiological and morphological state of host plants to promote successful pathogenesis. We show here that transgenic Nicotiana benthamiana lines expressing the secreted effector SAP11 from Candidatus Phytoplasma mali exhibit an altered aroma phenotype. This phenomenon is correlated with defects in the development of glandular trichomes and the biosynthesis of 3-isobutyl-2-methoxypyrazine (IBMP). IBMP is a volatile organic compound (VOC) synthesized by an O-methyltransferase, via a methylation step, from a non-volatile precursor, 3-isobutyl-2-hydroxypyrazine (IBHP). Based on comparative and functional genomics analyses, NbOMT1, which encodes an O methyltransferase, was found to be highly suppressed in SAP11-transgenic plants. We further silenced NbOMT1 through virus-induced gene silencing and demonstrated that this enzyme influenced the accumulation of IBMP in N. benthamiana In vitro biochemical analyses also showed that NbOMT1 can catalyse IBHP O-methylation in the presence of S-adenosyl-L-methionine. Our study suggests that the phytoplasma effector SAP11 has the ability to modulate host VOC emissions. In addition, we also demonstrated that SAP11 destabilized TCP transcription factors and suppressed jasmonic acid responses in N. benthamiana These findings provide valuable insights into understanding how phytoplasma effectors influence plant volatiles. PMID- 27279278 TI - The intergenic region of the maize defensin-like protein genes Def1 and Def2 functions as an embryo-specific asymmetric bidirectional promoter. AB - Bidirectional promoters are identified in diverse organisms with widely varied genome sizes, including bacteria, yeast, mammals, and plants. However, little research has been done on any individual endogenous bidirectional promoter from plants. Here, we describe a promoter positioned in the intergenic region of two defensin-like protein genes, Def1 and Def2 in maize (Zea mays). We examined the expression profiles of Def1 and Def2 in 14 maize tissues by qRT-PCR, and the results showed that this gene pair was expressed abundantly and specifically in seeds. When fused to either green fluorescent protein (GFP) or beta-glucuronidase (GUS) reporter genes, P ZmBD1 , P ZmDef1 , and P ZmDef2 were active and reproduced the expression patterns of both Def1 and Def2 genes in transformed immature maize embryos, as well as in developing seeds of transgenic maize. Comparative analysis revealed that PZmBD1 shared most of the expression characteristics of the two polar promoters, but displayed more stringent embryo specificity, delayed expression initiation, and asymmetric promoter activity. Moreover, a truncated promoter study revealed that the core promoters only exhibit basic bidirectional activity, while interacting with necessary cis elements, which leads to polarity and different strengths. The sophisticated interaction or counteraction between the core promoter and cis-elements may potentially regulate bidirectional promoters. PMID- 27279279 TI - Hydrothermal synthesis of a 3D double-sided comb-like ZnO nanostructure and its growth mechanism analysis. AB - Self-assembly of two-dimensional (2D) nanosheets and one-dimensional (1D) nanorods into three-dimensional (3D) double-sided comb-like ZnO nanostructures has been successfully performed via a simple one-step hydrothermal method on Si and ITO substrates. It is found that the thickness of the ZnO seeds plays a vital role in the formation of 3D double-sided comb-like ZnO. PMID- 27279280 TI - Host genetics determine susceptibility to avian influenza infection and transmission dynamics. AB - Host-genetic control of influenza virus infection has been the object of little attention. In this study we determined that two inbred lines of chicken differing in their genetic background , Lines 0 and C-B12, were respectively relatively resistant and susceptible to infection with the low pathogenicity influenza virus A/Turkey/England/647/77 as defined by substantial differences in viral shedding trajectories. Resistant birds, although infected, were unable to transmit virus to contact birds, as ultimately only the presence of a sustained cloacal shedding (and not oropharyngeal shedding) was critical for transmission. Restriction of within-bird transmission of virus occurred in the resistant line, with intra nares or cloacal infection resulting in only local shedding and failing to transmit fully through the gastro-intestinal-pulmonary tract. Resistance to infection was independent of adaptive immune responses, including the expansion of specific IFNgamma secreting cells or production of influenza-specific antibody. Genetic resistance to a novel H9N2 virus was less robust, though significant differences between host genotypes were still clearly evident. The existence of host-genetic determination of the outcome of influenza infection offers tools for the further dissection of this regulation and also for understanding the mechanisms of influenza transmission within and between birds. PMID- 27279281 TI - Prevalence and associated survival of high-risk HPV-related adenoid cystic carcinoma of the salivary glands. AB - Adenoid cystic carcinoma (SACC) is a rare malignancy, but a frequent subtype in minor and major salivary glands. The molecular alterations or biomarkers that underlie its development and progression as well as therapy outcomes are poorly characterized. The main study goal was to investigate reliable biomarkers and patient-related factors that may have impact on recurrence and long-term survival of SACC. The prevalence of human papilloma virus (HPV) in SACC was determined by HPV-DNA genotyping and p16 immunostaining. Epithelial growth factor receptor (EGFR), p53 and Ki-67 expression were also evaluated. Twenty-eight (42%) of 67 patients were HPV-DNA positive. Kaplan-Meier analysis indicated that SACC patients with metastases (P=0.03) had a poor overall survival (OS) and a shorter recurrence-free survival (P<0.001). Positive resection margins significantly predicted shorter recurrence-free survival (P=0.01). In the multivariate analysis, non-metastatic disease (P=0.033) and p16 positivity (P=0.005) have shown their prediction value for OS while non-metastatic disease (P=0.002), HPV positivity (P=0.041) and negative resection margin predicted a better recurrence free survival. The present study documents for the first time the positivity for HPV infection and overexpression of certain markers (p16, Ki-67, EGFR and p53) used in diagnostics in SACC as well as characterizes clinical entities. These factors might be exploited in the future as biomarkers for its prognostic value. Using the clinical and pathological basis for predicting different outcomes could significantly facilitate SACC stratification and potentially directing treatment. PMID- 27279282 TI - Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state. AB - This study evaluated whether crocin, a bioactive component of saffron, has a protective effect on kidney through reducing the oxidative stress and inflammatory response in aged rats. In this study the changes in activities of antioxidant enzymes, lipid peroxidation, glutathione (GSH) levels and the expression of pro-inflammatory cytokines in the serum and renal tissue were evaluated by ELISA and RT-PCR, respectively. The middle and aged rats were given intraperitoneal injections of crocin (10, 20, 30 mg/kg/day) for 4 weeks. After 4 weeks, animals were anesthetized with diethyl ether. The kidney samples were taken for biochemical analysis. The results revealed the aging was associated with a significant decrease in the activities of antioxidant enzymes, and GSH content with increase in lipid peroxidation level in kidney of the aged rats (p < 0.001). The increased levels of serum renal functional parameter, oxidative parameters (p < 0.01) and also pro-inflammatory cytokine levels were significantly reduced by crocin administration (p < 0.05). The aged rats exhibited a dysregulation of the oxidative stress, and inflammation in the kidneys, but crocin treatment significantly reduced the expression of the inflammatory genes. These results provide pivotal documentation that crocin has a renoprotective effects against the development of oxidative stress and inflammation in the kidney of old rats. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27279283 TI - Rapamycin suppresses microglial activation and reduces the development of neuropathic pain after spinal cord injury. AB - Rapamycin is an inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway, plays an important role in multiple cellular functions. Our previous study showed rapamycin treatment in acute phase reduced the neural tissue damage and locomotor impairment after spinal cord injury (SCI). However, there has been no study to investigate the therapeutic effect of rapamycin on neuropathic pain after SCI. In this study, we examined whether rapamycin reduces neuropathic pain following SCI in mice. We used a mouse model of thoracic spinal cord contusion injury, and divided the mice into the rapamycin-treated and the vehicle-treated groups. The rapamycin-treated mice were intraperitoneally injected with rapamycin (1 mg/kg) 4 h after SCI. The rapamycin treatment suppressed phosphorylated-p70S6K in the injured spinal cord that indicated inhibition of mTOR. The rapamycin treatment significantly improved not only locomotor function, but also mechanical and thermal hypersensitivity in the hindpaws after SCI. In an immunohistochemical analysis, Iba-1-stained microglia in the lumbar spinal cord was significantly decreased in the rapamycin-treated mice. In addition, the activity of p38 MAPK in the lumbar spinal cord was significantly attenuated by rapamycin treatment. Furthermore, phosphorylated-p38 MAPK-positive microglia was relatively decreased in the rapamycin-treated mice. These results indicated rapamycin administration in acute phase to reduce secondary neural tissue damage can contribute to the suppression of the microglial activation in the lumbar spinal cord and attenuate the development of neuropathic pain after SCI. The present study first demonstrated that rapamycin has significant therapeutic potential to reduce the development of neuropathic pain following SCI. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:93-103, 2017. PMID- 27279284 TI - Laser-Induced Breakdown Spectroscopy Coupled with Multivariate Chemometrics for Variety Discrimination of Soil. AB - The aim of this work was to analyze the variety of soil by laser-induced breakdown spectroscopy (LIBS) coupled with chemometrics methods. 6 certified reference materials (CRMs) of soil samples were selected and their LIBS spectra were captured. Characteristic emission lines of main elements were identified based on the LIBS curves and corresponding contents. From the identified emission lines, LIBS spectra in 7 lines with high signal-to-noise ratio (SNR) were chosen for further analysis. Principal component analysis (PCA) was carried out using the LIBS spectra at 7 selected lines and an obvious cluster of 6 soils was observed. Soft independent modeling of class analogy (SIMCA) and least-squares support vector machine (LS-SVM) were introduced to establish discriminant models for classifying the 6 types of soils, and they offered the correct discrimination rates of 90% and 100%, respectively. Receiver operating characteristic (ROC) curve was used to evaluate the performance of models and the results demonstrated that the LS-SVM model was promising. Lastly, 8 types of soils from different places were gathered to conduct the same experiments for verifying the selected 7 emission lines and LS-SVM model. The research revealed that LIBS technology coupled with chemometrics could conduct the variety discrimination of soil. PMID- 27279285 TI - The transcriptional regulator GalR self-assembles to form highly regular tubular structures. AB - The Gal repressor regulates transport and metabolism of D-galactose in Escherichia coli and can mediate DNA loop formation by forming a bridge between adjacent or distant sites. GalR forms insoluble aggregates at lower salt concentrations in vitro, which can be solubilized at higher salt concentrations. Here, we investigate the assembly and disassembly of GalR aggregates. We find that a sharp transition from aggregates to soluble species occurs between 200 and 400 mM NaCl, incompatible with a simple salting-in effect. The aggregates are highly ordered rod-like structures, highlighting a remarkable ability for organized self-assembly. Mutant studies reveal that aggregation is dependent on two separate interfaces of GalR. The highly ordered structures dissociate to smaller aggregates in the presence of D-galactose. We propose that these self assembled structures may constitute galactose-tolerant polymers for chromosome compaction in stationary phase cells, in effect linking self-assembly with regulatory function. PMID- 27279287 TI - 7-Difluoromethoxyl-5,4'-di-n-octyl genistein inhibits the stem-like characteristics of gastric cancer stem-like cells and reverses the phenotype of epithelial-mesenchymal transition in gastric cancer cells. AB - 7-Difluoromethoxyl-5,4'-di-n-octyl genistein (DFOG), a novel synthetic genistein analogue, exerts anticarcinogenic activity in several types of cancers, including gastric cancer. Accumulating evidence in recent years strongly indicates the existence of cancer stem cells in gastric cancer. The objective of the present study was to investigate whether DFOG inhibits the stemness and reverses the epithelial-mesenchymal transition (EMT) phenotype of gastric cancer stem-like cells (GCSLCs) derived from human gastric cancer SGC-7901 cells and to identify its potential mechanism. Sphere-forming cells (SFCs) from the SGC-7901 cells possessed the properties of GCSLCs. DFOG preferentially inhibited self-renewal, cell migration and cell invasion, and downregulated the expression of stem cell biomarkers in a dose-dependent manner. At the molecular level, these effects were accompanied by the downregulation of forkhead box M1 (FoxM1). Meanwhile, FoxM1 siRNA transfection was able to synergize the inhibition of expression of FoxM1 and Twist1 induced by DFOG in GCSLCs. In addition, we found that DFOG treatment decreased the expression of N-cadherin and increased the expression of E cadherin. More importantly, FoxM1 siRNA transfection cooperated with DFOG to suppress the self-renewal capacity, cell migration and cell invasion, and downregulated the expression of CD133, CD44, ALDH1, and also regulated the expression of N-cadherin and E-cadherin. These findings showed that DFOG inhibited the stem-like characteristics of GCSLCs and reversed the EMT phenotype by modulation of FoxM1 and further decreased Twist1 expression. Our results provide a further rationale and experimental basis for using DFOG to improve the efficacy of treatment for patients with gastric cancer. PMID- 27279286 TI - Human GPR4 and the Notch signaling pathway in endothelial cell tube formation. AB - G protein-coupled receptor 4 (GPR4) is hypothesized to function as a pH sensor and is important in the regulation of proliferation, migration and angiogenesis of vascular endothelial cells (ECs). Furthermore, the Notch signaling pathway is significant in the regulation of the angiogenic behavior of ECs. However, whether GPR4 regulates angiogenesis via the Notch signaling pathway remains unclear. The present study evaluated the effect of Notch signaling in human GPR4-induced angiogenesis in HMEC-1 cells. The results revealed that GPR4 increased Notch1 expression in a time-dependent manner. In addition, the inhibition of Notch1 expression using small interfering RNA or the Notch receptor inhibitor, gamma secretase inhibitor I, significantly blocked GPR4-induced HMEC-1 tube formation and lymphocyte transendothelial migration. Furthermore, the inhibition of Notch1 blocked GPR4-induced vascular endothelial growth factor and hypoxia-inducible factor 1alpha expression. Thus, it was demonstrated that GPR4 affects ECs by regulating Notch1, a function that may be important for physiological and pathological angiogenesis. PMID- 27279288 TI - A new phenolic glycoside from Saprosma merrillii. AB - A new phenolic glycoside derivative, saproglucoside (1), along with five known phenolic glycoside derivatives (2-6) were isolated from the stems of Saprosma merrillii. The structure of the new compound 1 was determined by 1D and 2D NMR as well as by HRESIMS and hydrolysis. The inhibitory activities of all compounds against seven pathogenic bacteria and two cancer cell lines were evaluated. PMID- 27279289 TI - Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma: An updated review of published data from the named patient program. AB - Brentuximab vedotin was available via named patient program (NPP) to patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma in ~60 non-US/Canadian countries, before local approval. Published results were examined recently; through systematic literature review, we identified 12 new NPP publications. Most (10/12) publications included new NPP data describing 8 unique cohorts (N=480; all R/R HL) and new participating countries. Overall response rates were 58-80%, and complete remission rates were 10-40%. With median follow-up of 9.5-26 months, median progression-free survival was 5-10.5 months and median overall survival (OS) had not been reached in most cohorts; 1- and 2-year OS was 67-76% and 58-67%, respectively. Tolerability was as expected from previous reports. Despite intrinsic bias and heterogeneous cohorts, this update supports previous findings showing comparable efficacy and tolerability of brentuximab vedotin between real-world practice and phase 2 trial results in R/R HL. PMID- 27279290 TI - Genetic heritage of Croatians in the Southeastern European gene pool-Y chromosome analysis of the Croatian continental and Island population. AB - OBJECTIVES: The research objective of this study is to enlarge and deepen the Y chromosome research on the Croatian population and enable additional insights into the population diversity and historic events that shaped the current genetic landscape of Croatia and Southeastern Europe (SEE). MATERIALS AND METHODS: A high resolution phylogenetic and phylogeographic analysis of 66 biallelic (SNPs) and 17 microsatellite (STRs) markers of the Y chromosome was performed using 720 Croatian samples. The obtained results were placed in a wider European context by comparison with ~4450 samples from a number of other European populations. RESULTS: A high diversity of haplogroups was observed in the overall Croatian sample, and all typical European Y chromosome haplogroups with corresponding clinal patterns were observed. Three distinct genetic signals were identifiable in the Croatian paternal gene pool - I2a1b-M423, R1a1a1b1a*-M558, and E1b1b1a1b1a V13 haplogroups. DISCUSSION: The analyses of the dominant and autochthonous I2a1b M423 lineage (>30%) suggest that SEE had a significant role in the Upper Paleolithic, the R1a1a1b1a*-M558 lineage (19%) represents a signal from present day Slavic populations of Central Europe in the Croatian population, and the phylogeography of the E1b1b1a1b1a-V13 clade (around 9%) implies cultural diffusion of agriculture into Europe via the Balkan Peninsula. Am. J. Hum. Biol., 2016. (c) 2016 Wiley Periodicals, Inc. Am. J. Hum. Biol. 28:837-845, 2016. (c) 2016Wiley Periodicals, Inc. PMID- 27279291 TI - Maternal behavior influences development of a reflexive action pattern in the newborn rat. AB - This study examined the effect of maternal behavior on the expression and postnatal development of a reflexive behavior in rat pups. In neonatal rats, the leg extension response (LER) is a bilateral hyperextension of the hindlimbs in response to maternal anogenital licking (AGL). Past research has found that intranasal application of zinc sulfate (ZnSO4 ) to the dam induces hyponosmia, thereby reducing the incidence of AGL. In this study, pregnant dams received intranasal application of air (control), distilled water (control), or ZnSO4 on the day before birth and every other day thereafter until postnatal day 9 (P9). The LER was experimentally evoked in pups, using a vibrotactile device, at P1, P5, or P10. Pups born to ZnSO4 -treated dams showed significantly shorter bilateral LER durations and significantly smaller ankle angles than pups born to control dams. Reduction of overall maternal AGL approached significance, and afternoon AGL was significantly reduced. These data suggest that maternal behavior influenced development of the LER in rat pups, demonstrating the influence of maternal care on behavioral development during the perinatal period. PMID- 27279292 TI - Designing artificial two dimensional electron lattice on metal surface: a Kagome like lattice as an example. AB - Recently, a new kind of artificial two dimensional (2D) electron lattice on the nanoscale, i.e. molecular graphene, has drawn a lot of interest, where the metal surface electrons are transformed into a honeycomb lattice via absorbing a molecular lattice on the metal surface [Gomes et al., Nature, 2012, 438, 306; Wang et al., Phys. Rev. Lett., 2014, 113, 196803]. In this work, we theoretically demonstrate that this technique can be readily used to build other complex 2D electron lattices on a metal surface, which are of high interest in the field of condensed matter physics. The main challenge to build a complex 2D electron lattice is that this is a quantum antidot system, where the absorbed molecule normally exerts a repulsive potential on the surface electrons. Thus, there is no straightforward corresponding relation between the molecular lattice pattern and the desired 2D lattice of surface electrons. Here, we give an interesting example about the Kagome lattice, which has exotic correlated electronic states. We design a special molecular pattern and show that this molecular lattice can transform the surface electrons into a Kagome-like lattice. The numerical simulation is conducted using a Cu(111) surface and CO molecules. We first estimate the effective parameters of the Cu/CO system by fitting experimental data of the molecular graphene. Then, we calculate the corresponding energy bands and LDOS of the surface electrons in the presence of the proposed molecular lattice. Finally, we interpret the numerical results by the tight binding model of the Kagome lattice. We hope that our work can stimulate further theoretical and experimental interest in this novel artificial 2D electron lattice system. PMID- 27279293 TI - Image quality for publication. PMID- 27279294 TI - Topical corticosteroids in dermatology. AB - Since their introduction, topical corticosteroids have become indispensable in the treatment of various dermatoses. Hydrocortisone was the first compound. Modifications in the basic structure generated in vivo activity and thus different topically active compounds were discovered. Apart from the Stoughton vasoconstrictor assay, various other methods are used for potency assessment of topical corticosteroids. Topical corticosteroides are classified based upon potency and action of these molecules. Mechanism of action at the cellular level and indications of topical corticosteroid use have been discussed. Various adverse effects often occur as an extension of their activity combined with inappropriate usage. Tachyphylaxis and contact allergy are potential problems in clinical practice. Newer compounds with improved risk-benefit ratio are available. PMID- 27279295 TI - Anatomical segmentations in all forms of vitiligo: A new dimension to the etiopathogenesis. AB - BACKGROUND: We have reported segmented lesions in acral vitiligo as well as in generalized vitiligo and thereby proposed somatic mosaicism as a predisposing feature in all forms of vitiligo. This study is a further attempt to characterize and understand such segmented lesions by screening a large series of patients. METHODS: We searched our electronic archives (from 2002 to 2014) and identified/reviewed the photos of 615 vitiligo patients inclusive of all clinical types. Over 3500 photographs were screened for patterns that were repeatedly seen in two or more patients and a composite picture of these were marked on a body map. RESULTS: Similar unilateral/bilateral segmented lesions were identified among all forms of vitiligo during relatively stable phases of the disease. These appeared to be related to small and large anatomical divisions of the body. In rapidly evolving disease on the trunk, the lesions conformed to Blaschkoid patterns. Several instances of stable mirror image lesions, symmetric incremental progressions and regressions were also recorded. LIMITATIONS: These are observations of a retrospective, single-center review which need to be substantiated further in larger prospective studies. CONCLUSION: Similar unilateral/bilateral segmented patterns delineating major/minor anatomical divisions of the body may indicate a preexisting developmental defect (such as mosaicism). PMID- 27279296 TI - Clinical efficacy of rituximab in the treatment of pemphigus: A retrospective study. AB - BACKGROUND: Pulsed corticosteroids have been used successfully for the management of pemphigus. However, prolonged use of glucocorticoids may be associated with adverse effects and some patients show a poor response to conventional therapy. Biologics have shown a promising role in such cases; however, there is limited data from the Indian subcontinent. OBJECTIVE: The primary objective was to assess the efficacy and adverse effects of rituximab in pemphigus. The secondary objective was to measure the cumulative doses of corticosteroids required for these patients. METHODS: We undertook a retrospective review of records of 25 pemphigus patients (pemphigus vulgaris: 21, pemphigus foliaceus: 4) who had received rituximab infusion (rheumatoid arthritis protocol in 21 patients, modified in 4). Oral prednisolone was administered in dosages up to 0.5 mg/kg of body weight and tapered over the next 3-4 months according to the disease activity. However, other immunosuppressive agents such as cyclophosphamide and azathioprine were continued for one year after clinical remission was achieved. RESULTS: Complete remission was observed in 22 (88%) patients. The mean time to disease control and complete remission was 1.10 and 4.36 months, respectively. Four (16%) patients experienced relapse after a mean duration of 11.75 months. The mean total dose of oral steroids administered was equivalent to 3535.64 mg of prednisolone. Exacerbation of disease was noted in two patients after the first dose of rituximab and infectious complications, pneumonia and cellulitis, developed in one patient each. LIMITATIONS: A small sample size, the retrospective nature of the study and unavailability of follow-up anti-desmoglein autoantibodies levels were limitations. CONCLUSION: Rituximab is an effective agent in the treatment of pemphigus. The use of rituximab enabled use of a lower initial dose of oral prednisolone in pemphigus and hence reduced its total cumulative dose. Severe side effects were rare. PMID- 27279297 TI - Keratoderma-like T cell dyscrasia: A report of 13 cases and its distinction from mycosis fungoides palmaris et plantaris. AB - BACKGROUND: Atypical epitheliotropic T cell lymphocytic infiltrates are commonly encountered in routine and consultative dermatopathology practices and typically do not represent mycosis fungoides. Other conditions can mimic certain light microscopic and phenotypic findings encountered in mycosis fungoides, comprising a diverse spectrum of conditions including the lymphomatoid drug reaction, collagen vascular disease, viral hypersensitivity reactions and cutaneous T cell dyscrasia. AIMS: To examine biopsies obtained from cutaneous T cell dyscrasia localized to the palms and soles and to evaluate whether it exhibits a morphologic and pathogenetic continuum with mycosis fungoides plantaris et palmaris. METHODS: We examined 13 biopsies showing an epidermotropic superficial lymphocytic infiltrate from thirteen patients who presented with a palmar and/or plantar keratoderma without other sites of cutaneous involvement. Conventional light microscopy, immunophenotyping and clonality studies were carried out. The clinical features were recorded. RESULTS: Biopsies showed a variably dense, superficial, angiocentric CD4 or CD8 dominant lymphocytic infiltrate accompanied by a non-destructive pattern of epidermotropism. Low-grade cerebriform atypia along with variable diminution in the expression of CD7 and CD62L was noted. In three cases, statins were suspected to be the cause. Due to lack of familiarity with the entity, treatment interventions were inconsistent and not aggressively pursued. There was no evidence of disease progression to mycosis fungoides in any case. LIMITATIONS: The limitations of this study include the lack of long-term follow up and information on the nature of the therapeutic interventions and responses to treatment. CONCLUSION: The spectrum of cutaneous lymphoid dyscrasias should be expanded to include cases manifesting as palmo-plantar keratoderma. These cases are to be distinguished from mycosis fungoides palmaris et plantaris. As with other forms of cutaneous lymphoid dyscrasia, the lesions tend to be persistent. The course however, is indolent in most cases. PMID- 27279298 TI - Metabolic syndrome in androgenic alopecia. AB - BACKGROUND: Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. AIM: To study the association between metabolic syndrome and early-onset androgenic alopecia. METHODS: A hospital-based analytical cross-sectional study was done on men in the age group of 18-55 years. Eighty five clinically diagnosed cases with early-onset (<35 years) androgenic alopecia of Norwood grade III or above, and 85 controls without androgenic alopecia were included. Data collected included anthropometric measurements, arterial blood pressure and history of chronic diseases. Fasting blood and lipid profile were determined. Metabolic syndrome was diagnosed as per the new International Diabetes Federation criteria. Chi-square and Student's t test were used for statistical analysis using Statistical Package for the Social Sciences (SPSS) version 17.00. RESULTS: Metabolic syndrome was seen in 19 (22.4%) patients with androgenic alopecia and 8 (9.4%) controls (P = 0.021). Abdominal obesity, hypertension and lowered high-density lipoprotein were significantly higher in patients with androgenic alopecia versus their respective controls. LIMITATIONS: The limitations of our study include small sample size in subgroups and the lack of evidence of a temporal relationship between metabolic syndrome and androgenic alopecia. CONCLUSION: A higher prevalence of metabolic syndrome is seen in men with early-onset androgenic alopecia. Early screening for metabolic syndrome and its components is beneficial in patients with early-onset androgenic alopecia. PMID- 27279299 TI - Imatinib induced melasma-like pigmentation: Report of five cases and review of literature. AB - Imatinib mesylate is a cytotoxic agent that targets tyrosine kinase. Common side effects of this drug include nausea, edema and maculopapular rash. Hypopigmentation is a commonly reported side effect of this drug while hyperpigmentation has rarely been described. We describe five cases of melasma like pigmentation induced by this anti-cancer drug. Four of the patients were diagnosed with gastrointestinal stromal tumor while one had chronic myeloid leukemia. Patients received imatinib mesylate in a dose of 400 mg daily. Over an average period of 3 months, well defined hyperpigmented macules appeared over the convexities of the face. One of the patients also developed similar pigmentation on the forearm. Other causes of hyperpigmentation were excluded in each patient. PMID- 27279300 TI - Angiolymphoid hyperplasia with arterial ectasia and arteriovenous malformation: Response to intra-arterial embolization. AB - Angiolymphoid hyperplasia with eosinophilia is a rare disease characterized by vascular proliferation of unknown origin. The lesions are mostly seen in the head and neck region and are characterized by papules or nodules. A 20-year-old man presented with a 1 year history of reddish papulo-nodular lesions overlying a pulsatile swelling on the left auricular area. Histopathology was suggestive of angiolymphoid hyperplasia with eosinophilia. B-mode ultrasonography, color Doppler and angiography revealed arterial ectasia and arteriovenous malformation of the left auricular artery. Such malformations have been reported previously, in association with angiolymphoid hyperplasia with eosinophilia. The cutaneous lesions responded well to transarterial embolization of the nidus. PMID- 27279301 TI - Post-traumatic ectopic nail. PMID- 27279302 TI - Immunotherapy or not? The mystery deepens. PMID- 27279303 TI - Authors' reply. PMID- 27279304 TI - Intralesional immunotherapy with tuberculin purified protein derivative for verruca: A study from a teaching hospital in South India. PMID- 27279305 TI - Total contact casting in the treatment of nonhealing plantar ulcers in anesthetic foot. PMID- 27279306 TI - Multifocal tuberculous gummas and bilateral scrofuloderma followed by papulonecrotic tuberculids developing during anti-tubercular therapy. PMID- 27279307 TI - Uncommon presentations of lupus miliaris disseminatus faciei. PMID- 27279308 TI - A novel missense mutation of the ATP2C1 gene in a Chinese patient with papular acantholytic dermatosis of the anogenital area. PMID- 27279309 TI - Spontaneous sublingual hematoma due to warfarin: An emergency presenting to the dermatologist. PMID- 27279310 TI - Sebaceous cell carcinoma developing in epidermodysplasia verruciformis. PMID- 27279311 TI - Down-regulation of peroxin synthesis by silencing RNA (siRNA): A novel hypothesis for treatment of leishmaniasis. PMID- 27279312 TI - Lionfish envenomation: Relapses controlled by intralesional triamcinolone. PMID- 27279314 TI - Multiple glomeruloid hemangiomas without POEMS syndrome. PMID- 27279313 TI - Juvenile IgA pemphigus: A case report and review of literature. PMID- 27279315 TI - Congenital absence of skin and an absent twin. PMID- 27279316 TI - An asymptomatic inguinal swelling: Lymphatic filariasis. PMID- 27279317 TI - Painful calcifying aponeurotic fibroma. PMID- 27279318 TI - Two cases of D-penicillamine-induced elastosis perforans serpiginosa. PMID- 27279319 TI - Two cases of axillary chromoblastomycosis. PMID- 27279320 TI - Angiolymphoid hyperplasia with eosinophilia treated with surgical excision and electrocoagulation forceps. PMID- 27279321 TI - Severe recalcitrant psoriasis treated with itolizumab, a novel anti-CD6 monoclonal antibody. PMID- 27279322 TI - Reticulate pigmentation in non-bullous ichthyosiform erythroderma. PMID- 27279323 TI - Yellowish-white papules in a cobblestone pattern on the neck. PMID- 27279324 TI - Annular lichenoid dermatitis of youth in a 15-year-old boy: Topical tacrolimus as a treatment option. PMID- 27279325 TI - Localized contact dermatitis from Ferula assa-foetida oleo-gum-resin essential oil, a traditional topical preparation for stomach ache and flatulence. PMID- 27279326 TI - Viva questions from the IJDVL. PMID- 27279327 TI - Near-future pH conditions severely impact calcification, metabolism and the nervous system in the pteropod Heliconoides inflatus. AB - Shelled pteropods play key roles in the global carbon cycle and food webs of various ecosystems. Their thin external shell is sensitive to small changes in pH, and shell dissolution has already been observed in areas where aragonite saturation state is ~1. A decline in pteropod abundance has the potential to disrupt trophic networks and directly impact commercial fisheries. Therefore, it is crucial to understand how pteropods will be affected by global environmental change, particularly ocean acidification. In this study, physiological and molecular approaches were used to investigate the response of the Mediterranean pteropod, Heliconoides inflatus, to pH values projected for 2100 under a moderate emissions trajectory (RCP6.0). Pteropods were subjected to pHT 7.9 for 3 days, and gene expression levels, calcification and respiration rates were measured relative to pHT 8.1 controls. Gross calcification decreased markedly under low pH conditions, while genes potentially involved in calcification were up-regulated, reflecting the inability of pteropods to maintain calcification rates. Gene expression data imply that under low pH conditions, both metabolic processes and protein synthesis may be compromised, while genes involved in acid-base regulation were up-regulated. A large number of genes related to nervous system structure and function were also up-regulated in the low pH treatment, including a GABAA receptor subunit. This observation is particularly interesting because GABAA receptor disturbances, leading to altered behavior, have been documented in several other marine animals after exposure to elevated CO2 . The up-regulation of many genes involved in nervous system function suggests that exposure to low pH could have major effects on pteropod behavior. This study illustrates the power of combining physiological and molecular approaches. It also reveals the importance of behavioral analyses in studies aimed at understanding the impacts of low pH on marine animals. PMID- 27279329 TI - Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles. AB - Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations. PMID- 27279328 TI - Effects of LDL Receptor Modulation on Lymphatic Function. AB - Atherosclerosis is driven by the accumulation of immune cells and cholesterol in the arterial wall. Although recent studies have shown that lymphatic vessels play an important role in macrophage reverse cholesterol transport, the specific underlying mechanisms of this physiological feature remain unknown. In the current report, we sought to better characterize the lymphatic dysfunction that is associated with atherosclerosis by studying the physiological and temporal origins of this impairment. First, we assessed that athero-protected Pcsk9(-/-) mice exhibited improved collecting lymphatic vessel function throughout age when compared to WT mice for up to six months, while displaying enhanced expression of LDLR on lymphatic endothelial cells. Lymphatic dysfunction was present before the atherosclerotic lesion formation in a mouse model that is predisposed to develop atherosclerosis (Ldlr(-/-); hApoB100(+/+)). This dysfunction was presumably associated with a defect in the collecting lymphatic vessels in a non-specific cholesterol- but LDLR-dependent manner. Treatment with a selective VEGFR-3 agonist rescued this impairment observed early in the onset of this arterial disease. We suggest that LDLR modulation is associated with early atherosclerosis related lymphatic dysfunction, and bring forth a pleiotropic role for PCSK9 in lymphatic function. Our study unveils new potential therapeutic targets for the prevention and treatment of atherosclerosis. PMID- 27279330 TI - Enhancement of anaerobic degradation of azo dye with riboflavin and nicotinamide adenine dinucleotide harvested by osmotic lysis of wasted fermentation yeasts. AB - The study presented here aims at identifying the source of redox mediators (riboflavin), electron carriers nicotinamide adenine dinucleotide (NAD) and carbon to perform decolorization of azo dye under anaerobic conditions after osmotic shock pretreatment of residual yeast from industrial fermentation. Pretreatment conditions were optimized by Doehlert experiment, varying NaCl concentration, temperature, yeast density and time. After the optimization, the riboflavin concentration in the residual yeast lysate (RYL) was 46% higher than the one present in commercial yeast extract. Moreover, similar NAD concentration was observed in both extracts. Subsequently, two decolorization experiments were performed, that is, a batch experiment (48 h) and a kinetic experiment (102 h). The results of the batch experiment showed that the use of the RYL produced by the optimized method increased decolorization rates and led to color removal efficiencies similar to those found when using the commercial extract (~80%) and from 23% to 50% higher when compared to the control (without redox mediators). Kinetics analysis showed that methane production was also higher in the presence of yeast extract and RYL, and biogas was mostly generated after stabilization of color removal. In all kinetics experiments the azo dye degradation followed the pseudo-second-order model, which suggested that there was a concomitant adsorption/degradation of the dye on the biomass cell surface. Therefore, results showed the possibility of applying the pretreated residual yeast to improve color removal under anaerobic conditions, which is a sustainable process. PMID- 27279331 TI - A bird's eye view of a deleterious recessive allele. AB - In the endangered Scottish chough (Pyrrhocorax pyrrhocorax) population, a lethal blindness syndrome is found to be caused by a deleterious recessive allele. Photo: Gordon Yates. In Focus: Trask, A.E., Bignal, E.M., McCracken, D.I., Monaghan, P., Piertney, S.B. & Reid, J.M. (2016) Evidence of the phenotypic expression of a lethal recessive allele under inbreeding in a wild population of conservation concern. Journal of Animal Ecology, 85, 879-891. In this issue of Journal of Animal Ecology, Trask et al. () report on a strange, lethal, blindness that regularly affects chicks of an endangered bird population. The authors show that the inheritance mode of this blindness disease precisely matches the expectations of a recessive deleterious mutation. Intriguingly, there is also an indication that the disease-causing variant might be maintained in the population by balancing selection, due to a selective advantage for heterozygotes. Could this finding have consequences for conservation actions implemented for the population? PMID- 27279332 TI - Colonization history and clonal richness of asexual Daphnia in periglacial habitats of contrasting age in West Greenland. AB - Due to climate change, Arctic ice sheets are retreating. This leads to the formation of numerous new periglacial ponds and lakes, which are being colonized by planktonic organisms such as the water flea Daphnia. This system provides unique opportunities to test genotype colonization dynamics and the genetic assemblage of populations. Here, we studied clonal richness of the Daphnia pulex species complex in novel periglacial habitats created by glacial retreat in the Jakobshavn Isbrae area of western Greenland. Along a 10 km transect, we surveyed 73 periglacial habitats out of which 61 were colonized by Daphnia pulex. Hence, for our analysis, we used 21 ponds and 40 lakes in two clusters of habitats differing in age (estimated <50 years vs. >150 years). We tested the expectation that genetic diversity would be low in recently formed (i.e. young), small habitats, but would increase with increasing age and size. We identified a total of 42 genetically distinct clones belonging to two obligately asexual species of the D. pulex species complex: D. middendorffiana and the much more abundant D. pulicaria. While regional clonal richness was high, most clones were rare: 16 clones were restricted to a single habitat and the five most widespread clones accounted for 68% of all individuals sampled. On average, 3.2 clones (range: 1 12) coexisted in a given pond or lake. There was no relationship between clonal richness and habitat size when we controlled for habitat age. Whereas clonal richness was statistically higher in the cluster of older habitats when compared with the cluster of younger ponds and lakes, most young habitats were colonized by multiple genotypes. Our data suggest that newly formed (periglacial) ponds and lakes are colonized within decades by multiple genotypes via multiple colonization events, even in the smallest of our study systems (4 m(2) ). PMID- 27279333 TI - Corrigendum. PMID- 27279335 TI - Long-term patient satisfaction after retropubic and transobturator mid-urethral slings for female stress urinary incontinence. AB - AIM: The aim of this study was to report long-term patient outcomes after retropubic and transobturator mid-urethral slings for female stress urinary incontinence. METHODS: Women who underwent mid-urethral sling for stress urinary incontinence between 2000 and 2010 were invited to participate in a survey regarding their overall improvement. Patients' outcomes were assessed using the International Consultation on Incontinence Questionnaire - Short Form and the Global Response Assessment Scale. RESULTS: The questionnaires were completed by 330 patients. Their median age at the time of surgery was 54.8 years (+/-12.9) and the median follow-up period was 11.9 years (+/-6.4). Retropubic and transobturator approaches were performed in 128 (38.8%) and 202 (61.2%) patients, respectively. The International Consultation on Incontinence Questionnaire - Short Form score dropped from an average of 14 (+/-4.1) to 6.4 (+/-6) with no significant difference between the two groups. The Global Response Assessment Scale showed an 9% greater improvement in the retropubic (66.4%) over the transobturator (57.4%) approach. De novo overactive bladder was the commonest long-term reported adverse event, affecting 18/330 patients (5.5%). Voiding dysfunction that required surgical correction following the retropubic approach occurred in three patients (2.3%). CONCLUSION: Mid-urethral slings for the management of female stress urinary incontinence had good and durable long-term effects. Although the retropubic approach gave better results, they were not significantly different than those of the transobturator approach. PMID- 27279334 TI - SURVIV for survival analysis of mRNA isoform variation. AB - The rapid accumulation of clinical RNA-seq data sets has provided the opportunity to associate mRNA isoform variations to clinical outcomes. Here we report a statistical method SURVIV (Survival analysis of mRNA Isoform Variation), designed for identifying mRNA isoform variation associated with patient survival time. A unique feature and major strength of SURVIV is that it models the measurement uncertainty of mRNA isoform ratio in RNA-seq data. Simulation studies suggest that SURVIV outperforms the conventional Cox regression survival analysis, especially for data sets with modest sequencing depth. We applied SURVIV to TCGA RNA-seq data of invasive ductal carcinoma as well as five additional cancer types. Alternative splicing-based survival predictors consistently outperform gene expression-based survival predictors, and the integration of clinical, gene expression and alternative splicing profiles leads to the best survival prediction. We anticipate that SURVIV will have broad utilities for analysing diverse types of mRNA isoform variation in large-scale clinical RNA-seq projects. PMID- 27279337 TI - Current Trends in Self-Emulsifying Drug Delivery Systems (SEDDSs) to Enhance the Bioavailability of Poorly Water-Soluble Drugs. AB - The main object of the self-emulsifying drug-delivery system (SEDDS) is oral bioavailability (BA) enhancement of a poorly water-soluble drug. Low aqueous solubility and low oral BA are major concerns for formulation scientists. As many drugs are lipophilic in nature, their lower solubility and dissolution are major drawbacks for their successful formulation into oral dosage forms. More than 60% of drugs have a lipophilic nature and exhibit poor aqueous solubility. Various strategies are reported in the literature to improve the solubility and enhance BA of lipophilic drugs, including the formation of a cyclodextrin complex, solid dispersions, and micronization. SEDDSs are ideally isotropic mixtures of drug, oil, surfactant, and/or cosurfactant. SEDDSs have gained increasing attention for enhancing oral BA and reducing drug dose. SEDDSs also provide an effective and excellent solution to the various issues related to the formulation of hydrophobic drugs that have limited solubility in gastrointestinal fluid. Our major focus of this review is to highlight the importance of SEDDSs in oral BA enhancement of poorly water-soluble drugs. PMID- 27279336 TI - Identification and tissue expression profile of genes from three chemoreceptor families in an urban pest, Periplaneta americana. AB - Periplaneta americana is a notorious urban pest prevalent in human habitats; very little is known about its chemosensory mechanism. Employing the advanced next generation sequencing technique, in the present study, we conducted transcriptome sequencing and analysis of the antennae of the adult males and females as well as their mouthparts using an Illumina platform. This resulted in the discovery of a huge number of the members of all major known chemosensory receptor families in P. americana, including 96 odorant receptors (ORs), 53 ionotropic receptors (IRs), and 33 gustatory receptors (GRs). Tissue expression profiles showed most of them mainly expressed in antennae and phylogenetic analysis demonstrated the expansion in the clade distinguishing them from other functionally well-known Lepidoptera species. A high percentage of chemosensory receptor genes (ORs in particular) showing female antenna bias in mRNA expression was observed. Our results provide a basis for further investigations on how P. americana coordinates its chemosensory receptor genes in chemical communication with environments, and for development of novel pest management approaches. PMID- 27279338 TI - The Effective Role of Hydroxyapatite Based Composites in Anticancer Drug Delivery Systems. AB - Tumors consist of a heterogeneous population of cancer cells carrying multiple genetic mutations. During the past few decades, efforts have focused on curing cancer using various methods. However, traditional cancer therapies still carry some drawbacks, such as limited application for only a few cancer types, killing of normal cells, poor specificity, and associated toxicity. To overcome these disadvantages, drug-delivery methods that emphasize biomaterials have been developed and applied to optimize cancer treatments. Hydroxyapatite (HAP) is a biocompatible inorganic material that can be applied in biomedical drug-delivery applications. This review discusses the features and properties of HAP that make it an effective biomaterial and provides a comprehensive summary of recent studies in which HAP and composites containing HAP were applied as anticancer drug carriers. We believe that HAP-based composites show great promise for cancer treatment using controlled release of therapeutic agents, leading to enhanced efficiency, selective release of drugs, and prohibition of cancer cell proliferation. PMID- 27279339 TI - Microsponges: A Pioneering Tool for Biomedical Applications. AB - Microparticulate drug delivery systems have been explored across the globe due to their various advantages. In 1987, Won developed microsponge systems (Micsys), also known as solid-phase porous microspheres, having numerous interconnected voids, which serve as non-collapsible residence for bioactive compounds. A Micsys particle ranges from 5 to 300 MUm in size and shows a wide range of entrapment efficiency with desired release rates. This topical drug delivery system bestows a controlled release of bioactive compounds into the skin with reduced systemic side effects. Currently, the application fields of this promising system include oral, ocular, pulmonary, and parenteral delivery of bioactive compounds. In the present review, we summarize the updated biomedical application potential of Micsys as an effective drug-delivery vector, including an in-depth explanation of the drug-release kinetic models and drug-release mechanisms. We also discuss different techniques used to prepare a Micsys, along with their advantages and disadvantages. Moreover, in this review, we report a plethora of Micsys details, such as drug candidates and polymers, exploited in this field, along with marketed formulations, characterization methods, clinical perspectives, and patents received. This assembly of detailed literature summaries will contribute to future advances in the development of porous carriers. PMID- 27279340 TI - Histone acetylation is involved in TCDD-induced cleft palate formation in fetal mice. AB - The aim of the present was to evaluate the effects of DNA methylation and histone acetylation on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cleft palate in fetal mice. Pregnant mice (n=10) were randomly divided into two groups: i) TCDD group, mice were treated with 28 ug/kg TCDD on gestation day (GD) 10 by oral gavage; ii) control group, mice were treated with an equal volume of corn oil. On GD 16.5, the fetal mice were evaluated for the presence of a cleft palate. An additional 36 pregnant mice were divided into the control and TCDD groups, and palate samples were collected on GD 13.5, GD 14.5 and GD 15.5, respectively. Transforming growth factor-beta3 (TGF-beta3) mRNA expression, TGF-beta3 promoter methylation, histone acetyltransferase (HAT) activity and histone H3 (H3) acetylation in the palates were evaluated in the two groups. The incidence of a cleft palate in the TCDD group was 93.55%, and no cases of cleft palate were identified in the control group. On GD 13.5 and GD 14.5, TGF-beta3 mRNA expression, HAT activity and acetylated H3 levels were significantly increased in the TCDD group compared with the control. Methylated bands were not observed in the TCDD or control groups. In conclusion, at the critical period of palate fusion (GD 13.5-14.5), TCDD significantly increased TGF-beta3 gene expression, HAT activity and H3 acetylation. Therefore, histone acetylation may be involved in TCDD-induced cleft palate formation in fetal mice. PMID- 27279341 TI - Drug safety evaluation of roflumilast for the treatment of COPD: a meta-analysis. AB - INTRODUCTION: Roflumilast is the only phosphodiesterase 4 inhibitor approved for the treatment of COPD patients with chronic cough and sputum, and a history of exacerbations, but the compliance to treatment is reduced by poorly tolerated adverse events (AEs). AREAS COVERED: The synthesis of clinical evidences indicates that roflumilast 500MUg once-daily increased the risk of AEs, with no impact on the risk of serious AEs (SAEs), compared with placebo. Gastrointestinal AEs were common in patients treated with roflumilast, that may also induce headache, backpain and insomnia. Roflumilast protects against COPD related AEs. The frequency of very SAEs was rare but greater in patients treated with roflumilast than placebo, although factors other than the study drug were related with these SAEs. EXPERT OPINION: The safety profile of roflumilast administered in combination with further drugs for the treatment of COPD should be investigated through specifically designed RCTs, and the post-marketing surveillance might help to characterize the real risk of very SAEs. Roflumilast may provide more benefit than harm in patients at high risk of severe exacerbations, and the therapy discontinuation may be reduced by a correct education of patients on the generally transient and mild-to-moderate nature of gastrointestinal AEs induced by this drug. PMID- 27279342 TI - IgG/IgM antiphospholipid antibodies present in the classification criteria for the antiphospholipid syndrome: a critical review of their association with thrombosis. AB - Essentials The clinical value of IgM antibodies in thrombotic antiphospholipid syndrome (APS) is debated. By review of literature, we reconsidered the clinical value of IgM antibodies in thrombotic APS. More significant correlations with thrombosis were found for the IgG compared to IgM isotype. Unavailability of paired IgG/IgM results hampers evaluating the added value of IgM positivity. Click to hear Dr de Groot's perspective on antiphospholipid syndrome SUMMARY: Background Despite the update of the classification criteria for the antiphospholipid syndrome (APS), difficulties persist in the identification of patients at risk for thrombosis. Current guidelines include assays detecting IgG/IgM anti-beta2 -glycoprotein I and anti-cardiolipin antibodies, although the relevance of IgM antibodies has been debated. Objectives Through a review of the literature from 2001 to 2014, we aimed to formally establish the thrombotic risk stratification potential of IgM as compared with IgG anti-phospholipid antibodies (aPLs). Patients/methods One thousand two hundred and twenty-eight articles were selected by a computer-assisted search of the literature. Of the 177 studies that met our inclusion criteria, the clinical value of IgG/IgM aPLs was established through analysis of odds ratios for thrombosis or percentage of positives in the thrombotic population. Results/conclusions We clearly found more significant correlations with thrombosis for the IgG than for the IgM isotype. Nonetheless, in a minority of studies, significant associations with thrombosis were found for IgM but not IgG antibodies. The unavailability of paired results of IgG and IgM for each separate patient hampers evaluation of the added value of isolated IgM positivity. To fully take advantage of results obtained by future studies, we strongly encourage scientists to provide all studied information per patient. We planned a large multicenter study to investigate clinical associations of isolated/combined positivity for criteria/non-criteria aPLs. Importantly, because of the presence of non-pathogenic aPLs, quantitative assays are characterized by a high false-positivity rate. Optimization of functional assays, such as thrombin generation measuring the whole scheme of coagulation, may help to reduce APS related morbidity and mortality. PMID- 27279343 TI - Barriers to and motivators for physical activity among people with Type 2 diabetes: patients' perspectives. AB - AIM: To explore barriers to and motivators for physical activity in a group of overweight and obese individuals with dysregulated Type 2 diabetes. METHODS: Data were collected from the Steno Diabetes Center's outpatient clinic in Denmark. Four focus groups were conducted including 28 individuals with Type 2 diabetes aged 39-71 years. The facilitators used open-ended questions and probes such as images, statements and quotations about physical activity to foster active participation and interaction among participants. Focus groups were recorded on video and the discussions were transcribed and analysed thematically. RESULTS: We identified four main themes: 1) the body as a barrier to physical activity because of functional limitations; 2) logistical challenges, including lack of time and awareness of where to exercise in the local area; 3) being physically active with others, providing a sense of mutual commitment and enjoyment; and 4) goal-setting and self-tracking, which was seen as an opportunity to track physical improvement over time. CONCLUSIONS: The findings suggest that, once people are active, a high level of social interaction may help maintain their activity levels. Further research is needed to investigate the effect of combining individually tailored exercise plans with the establishment of customized and locally based exercise communities that offer enjoyment and support. Additionally, it is relevant to explore experiences of using self tracking technologies to review short- and long-term goals. PMID- 27279344 TI - Societal costs of fetal alcohol syndrome in Sweden. AB - OBJECTIVE: To estimate the annual societal cost of fetal alcohol syndrome (FAS) in Sweden, focusing on the secondary disabilities thought feasible to limit via early interventions. METHODS: Prevalence-based cost-of-illness analysis of FAS in Sweden for 2014. Direct costs (societal support, special education, psychiatric disorders and alcohol/drug abuse) and indirect costs (reduced working capacity and informal caring), were included. The calculations were based on published Swedish studies, including a register-based follow-up study of adults with FAS, reports and databases, and experts. RESULTS: The annual total societal cost of FAS was estimated at ?76,000 per child (0-17 years) and ?110,000 per adult (18-74 years), corresponding to ?1.6 billion per year in the Swedish population using a prevalence of FAS of 0.2 %. The annual additional cost of FAS (difference between the FAS group and a comparison group) was estimated at ?1.4 billion using a prevalence of 0.2 %. The major cost driver was the cost of societal support. CONCLUSIONS: The cost burden of FAS on the society is extensive, but likely to be underestimated. A reduction in the societal costs of FAS, both preventive and targeted interventions to children with FAS, should be prioritized. That is, the cost of early interventions such as placement in family homes or other forms of housing, and special education, represent unavoidable costs. However, these types of interventions are highly relevant to improve the individual's quality of life and future prospects, and also, within a long-term perspective, to limit the societal costs and personal suffering. PMID- 27279345 TI - Repression of Smad4 by miR-205 moderates TGF-beta-induced epithelial-mesenchymal transition in A549 cell lines. AB - The TGF-beta/Smad signaling pathway plays important roles in cancer cell proliferation, apoptosis, differentiation, angiogenesis and epithelial mesenchymal transition (EMT), which is the key event in the early stages of cancer metastasis and enhances the capability of cell migration and invasion. Smad4 acts as the only Co-Smad of TGF/Smad signaling pathway and plays the key role in TGF-beta-mediated EMT. Nevertheless, the mRNA regulation mechanisms of Smad4 in human non-small cell lung cancer (NSCLC) remains largely unclear. Computational algorithms predicted that the 3'-UTR of Smad4 is a target of miR 205. Here, we validated that miR-205 could directly bind to 3'-UTR of Smad4 by luciferase assays. Moreover, we investigated the functional roles of miR-205 and its molecular link to Smad4 in lung cancer cells. In this study, we confirmed that overexpression of miR-205 suppressed the expression of Smad4, in turn, weakened the TGF-beta/Smad signaling pathway and inhibited TGF-beta/Smad4-induced EMT, invasion and migration ultimately. Furthermore, this study shows that miR 205 can serve as a promising therapeutic target of highly aggressive NSCLC. PMID- 27279346 TI - Cardiovascular screening to reduce the burden from cardiovascular disease: microsimulation study to quantify policy options. AB - OBJECTIVES: To estimate the potential impact of universal screening for primary prevention of cardiovascular disease (National Health Service Health Checks) on disease burden and socioeconomic inequalities in health in England, and to compare universal screening with alternative feasible strategies. DESIGN: Microsimulation study of a close-to-reality synthetic population. Five scenarios were considered: baseline scenario, assuming that current trends in risk factors will continue in the future; universal screening; screening concentrated only in the most deprived areas; structural population-wide intervention; and combination of population-wide intervention and concentrated screening. SETTING: Synthetic population with similar characteristics to the community dwelling population of England. PARTICIPANTS: Synthetic people with traits informed by the health survey for England. MAIN OUTCOME MEASURE: Cardiovascular disease cases and deaths prevented or postponed by 2030, stratified by fifths of socioeconomic status using the index of multiple deprivation. RESULTS: Compared with the baseline scenario, universal screening may prevent or postpone approximately 19 000 cases (interquartile range 11 000-28 000) and 3000 deaths (-1000-6000); concentrated screening 17 000 cases (9000-26 000) and 2000 deaths (-1000-5000); population-wide intervention 67 000 cases (57 000-77 000) and 8000 deaths (4000 11 000); and the combination of the population-wide intervention and concentrated screening 82 000 cases (73 000-93 000) and 9000 deaths (6000-13 000). The most equitable strategy would be the combination of the population-wide intervention and concentrated screening, followed by concentrated screening alone and the population-wide intervention. Universal screening had the least apparent impact on socioeconomic inequalities in health. CONCLUSIONS: When primary prevention strategies for reducing cardiovascular disease burden and inequalities are compared, universal screening seems less effective than alternative strategies, which incorporate population-wide approaches. Further research is needed to identify the best mix of population-wide and risk targeted CVD strategies to maximise cost effectiveness and minimise inequalities. PMID- 27279347 TI - A systems biology and proteomics-based approach identifies SRC and VEGFA as biomarkers in risk factor mediated coronary heart disease. AB - Coronary heart disease (CHD) is the most common cause of death worldwide. The burden of CHD increases with risk factors such as smoking, hypertension, obesity and diabetes. Several studies have demonstrated the association of these classical risk factors with CHD. However, the mechanisms of these associations remain largely unclear due to the complexity of disease pathophysiology and the lack of an integrative approach that fails to provide a definite understanding of molecular linkage. To overcome these problems, we propose a novel systems biology approach that relates causative genes, interactomes and pathways to elucidate the risk factors mediating the molecular mechanisms and biomarkers for feasible diagnosis. The literature was mined to retrieve the causative genes of each risk factor and CHD to construct protein interactomes. The interactomes were examined to identify 298 common molecular signatures. The common signatures were mapped to the tissue network to synthesize a sub-network consisting of 82 proteins. Further, the dissection of the sub-network provides functional modules representing a diverse range of molecular functions, including the AKT/p13k, MAPK and wnt pathways. Also, the prioritization of functional modules identifies SRC, VEGFA and HIF1A as potential candidate markers. Further, we validate these candidates with the existing markers CRP, NOS3 and VCAM1 in the serum of 63 individuals, 33 with CHD and 30 controls, using ELISA. SRC, VEGFA, H1F1A, CRP and NOS3 were significantly altered in patients compared to controls. These results support the utility of these candidate markers for the diagnosis of CHD. Overall, our molecular observations indicate the influence of risk factors in the pathophysiology of CHD and identify serum markers for diagnosis. PMID- 27279348 TI - A model for pattern deposition from an evaporating solution subject to contact angle hysteresis and finite solubility. AB - We propose a model for the pattern deposition of the solute from an evaporating drop of a dilute solution on a horizontal substrate. In the model we take into account the three-phase contact angle hysteresis and the deposition of the solute whenever its concentration exceeds the solubility limit. The evaporating drop is governed by a film equation. We show that unless for a very small three-phase contact angle or a very rapid evaporation rate the film adopts a quasi-steady geometry, satisfying the Young-Laplace equation to leading order. The concentration profile is assumed to satisfy an advection diffusion equation subject to the standard Fick's law for the diffusive flux. We further use an integral boundary condition to describe the dynamics of the concentration in the vicinity of the three-phase contact line; we replace an exact geometric description of the vicinity of the contact line, which is usually assumed such that mathematical singularities are avoided, with general insights about the concentration and its flux. We use our model to explore the relationships between a variety of deposition patterns and the governing parameters, show that the model repeats previous findings, and suggest further insights. PMID- 27279349 TI - Letter to the Editor: Postpartum psychosis and pre-eclamptic toxaemia. PMID- 27279350 TI - The Inference-Based Approach (IBA) to the Treatment of Obsessive-Compulsive Disorder: An Open Trial Across Symptom Subtypes and Treatment-Resistant Cases. AB - : The current open trial evaluated an inference-based approach (IBA) to the treatment of obsessive-compulsive disorder (OCD) across symptom subtypes and treatment-resistant cases. Following formal diagnosis through semi-structured interview by an independent evaluator, a total of 125 OCD participants across five major symptom subtypes entered a program of 24 sessions of treatment based on the IBA. An additional group of 22 participants acted as a natural wait-list control group. Participants were administered the Yale-Brown Obsessive-Compulsive Scale before and after treatment as the principal outcome measure, as well as measures of negative mood states, inferential confusion and obsessive beliefs. Level of overvalued ideation was assessed clinically at pre-treatment using the Overvalued Ideation Scale. After 24 weeks of treatment, 102 treatment completers across all major subtypes of OCD showed significant reductions on the Yale-Brown Obsessive-Compulsive Scale with effect sizes ranging from 1.49 to 2.53 with a clinically significant improvement in 59.8% of participants. No improvement was observed in a natural wait-list comparison group. In addition, IBA was effective for those with high levels of overvalued ideation. Change in inferential confusion and beliefs about threat and responsibility were uniquely associated with treatment outcome. The study is the first large-scale open trial showing IBA to be effective across symptom subtypes and treatment-resistant cases. The treatment may be particularly valuable for those who have previously shown an attenuated response to other treatments. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Psychological treatment based on the inference based approach is an effective treatment for all major subtypes of obsessive compulsive disorder. The treatment is equally effective for those with high and low levels of overvalued ideation. Treatment based on the inference-based approach may be particularly valuable for those who have shown an attenuated response to cognitive-behaviour therapy as usual. PMID- 27279351 TI - Determination of iohexol and iothalamate in serum and urine by capillary electrophoresis. AB - Estimation of glomerular filtration rate (eGFR) is essential to assess kidney function. Iodine-containing contrast agents detection by HPLC has been proposed as a safe alternative for inulin or radioactive compounds. However, HPLC is a time-consuming and labor-intensive method. The aim of this study was to develop an assay for iohexol and iothalamate using capillary electrophoresis. Iohexol and iothalamate were directly analyzed by CE in serum and urine, using photometric detection (246 nm). Serum peak height was proportional to iohexol and iothalamate concentrations. Detection limits for iohexol and iothalamate were 10 and 5 mg/L. Limits of quantification were 13.0 and 15.0 mg/L. Within-run CVs were 4.9 and 6.5%; between-run CVs 3.1-9.9% and 3.8-13.7%. A good correlation was observed between CE and HPLC: y = 1.1703x + 5.017 (iohexol) and y = 0.7807x + 11.01 (iothalamate; (y = concentration obtained by CE [mg/L], x = concentration obtained by HPLC [mg/L]). In addition, CE allowed to determine urinary iohexol concentration. Although the detection limit for CE was higher than for HPLC, CE can still be used for eGFR determination. Advantages of this high-throughput method are the absence of sample pretreatment and a minimal sample volume requirement. PMID- 27279353 TI - Thirty-year stability after regeneration of a deep intrabony defect: a case report. AB - AIMS: Report clinical improvements and 30-year stability of clinical outcomes of an intrabony defect treated with non-resorbable barriers and mucogingival surgery. METHODS: A 18-year-old male presenting with a very severe intrabony defect at the upper right central incisor was treated with periodontal regeneration with non-resorbable barriers and a fibrin-fibronectin glue. The barriers were removed after 3 months. At 6 months, a free gingival graft (FGG) was positioned to improve mucogingival conditions. The patient was enrolled into a 6-month supportive periodontal care programme (SPC) for 30 years. RESULTS: Clinical attachment level (CAL) of 16 mm was associated with a 12 mm osseous defect and a pocket (PD) 14 mm deep. At 1 year, a CAL of 5 mm was associated with a PD of 2 mm. The 5 mm gingival recession measured at 6 months and treated with FGG was reduced to 3 mm. Measurements taken at 10, 20 and 30 years showed a consistent creeping of the gingival margin. At 30-year examination, CAL gain was 12 mm associated with a 2 mm PD and a minimal gingival recession. CONCLUSIONS: This case demonstrates that it is possible to treat a very severe infrabony pocket applying regeneration and mucogingival surgery and to maintain the clinical outcomes for 30 years. PMID- 27279352 TI - Influence of Breed Size, Age, Fecal Quality, and Enteropathogen Shedding on Fecal Calprotectin and Immunoglobulin A Concentrations in Puppies During the Weaning Period. AB - BACKGROUND: Fecal calprotectin and immunoglobulin A (IgA) are markers of intestinal inflammation and immunity in adult dogs. HYPOTHESIS: Fecal calprotectin and IgA concentrations in puppies are not influenced by fecal moisture in puppies but by enteropathogen shedding. ANIMALS: Three hundred and twenty-four puppies. METHODS: Fecal consistency was assessed by gross examination. Fecal moisture was evaluated before and after lyophilization. Canine parvovirus and coronavirus were detected in feces by qPCR and qRT-PCR respectively. Giardia intestinalis antigen was quantified by ELISA. The standard McMaster flotation technique was used to detect eggs and oocysts in feces. Fecal calprotectin and IgA concentrations were quantified by in-house radioimmunoassays. RESULTS: For each marker (IgA and calprotectin), a strong positive correlation was observed between concentration in fresh feces and concentration in fecal dry matter. 75.6% of the puppies were found to be infected by at >=1 of the enteropathogens evaluated. Fecal calprotectin concentration was significantly influenced by age (P = .001), with higher concentrations in younger puppies, but not by viral (P = .863) or parasitic infection (P = .791). Fecal IgA concentration was significantly influenced by enteropathogen shedding (P = .01), with a lower fecal IgA concentration in puppies shedding at >=1 enteropathogen compared to puppies without any enteropathogen shedding, but not by age. CONCLUSIONS: Fecal calprotectin and IgA are of no diagnostic value to detect presence of enteropathogens in clinically healthy puppies or puppies with abnormal feces, but could help to better understand the maturation of digestive tract. PMID- 27279354 TI - GP utilisation by education level among adults with COPD or asthma: a cross sectional register-based study. AB - There is a marked socioeconomic gradient in the prevalence of chronic obstructive pulmonary disease (COPD) and asthma, but a large proportion of patients remain undiagnosed. It is a challenge for general practitioners (GPs) to both identify patients and contribute to equity and high quality in services delivered. The aim of this study was to identify patients with COPD and asthma diagnoses recorded by GPs and explore their utilisation of GP services by education level. This was a cross-sectional, national, register-based study from Norwegian general practice in the period 2009-2011. Based on claims from GPs, the number of patients aged ?40 years with a diagnosis of COPD or asthma and their GP services utilisation were estimated and linked to the national education database. Multivariate Poisson and logistic regression models were used to explore the variations in GP utilisation. In the population aged ?40 years, 2.8% had COPD and 3.8% had asthma according to GPs' diagnoses. COPD was four times more prevalent in patients with basic education than higher education; this increase was ?80% for asthma. Consultation rates were 12% higher (P<0.001) for COPD and 25% higher (P<0.001) for asthma in patients with low versus high education in the age group of 40-59 years after adjusting for comorbidity, and patient and GP characteristics. Approximately 25% of COPD patients and 20% of asthma patients had ?1 spirometry test in general practice in 2011, with no significant education differences in adjusted models. The higher consultation rate in lower-education groups indicates that GPs contribute to fair distribution of healthcare. PMID- 27279355 TI - The cost-effectiveness of treating triple coinfection with HIV, tuberculosis and hepatitis C virus. AB - OBJECTIVES: The objective of this study was to estimate the cost-effectiveness of treating patients infected with HIV and simultaneously coinfected with tuberculosis (TB) and hepatitis C virus (HCV). METHODS: A mathematical model for HIV coinfection with TB and HCV is introduced. The model was designed to incorporate parameters of control for the coverage of care, which makes it useful for performing cost-effectiveness analysis of public policies. A cost effectiveness analysis of early medical care of patients with TB and HCV coinfection, with coverage of 0 (basal), 25, 50, 75 and 100%, was performed for the whole cohort of patients and a special analysis was performed in a selected population with triple infection. RESULTS: The cost per resolved infection and the cost per year of life gained were found to be very cost-effective for the population with triple infection, for all different coverages. CONCLUSIONS: It is known that treating patients with HIV who are coinfected with TB or HCV implies high cost and low efficacy, but it is possible that the population with triple infections could achieve important benefits in terms of years of life gained. PMID- 27279356 TI - Increased RANKL expression in peripheral T cells is associated with decreased bone mineral density in patients with COPD. AB - Receptor activator of nuclear factor-kappaB ligand (RANKL)-expressing adaptive T cells contribute to bone damage in autoimmune arthritis, although their role in chronic obstructive pulmonary disease (COPD)-associated osteoporosis is unknown. In the present study, the functional expression of RANKL in CD4+/CD8+ T cells and Th17 cells, and the potential role of these cells in COPD-associated bone loss was investigated. A total of 36 non-smokers, 38 smokers with normal lung function and 57 patients with COPD were enrolled. Femoral and vertebral bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. RANKL expression in peripheral CD4+ and CD8+ T cells and Th17 cells was evaluated by flow cytometry. For in vitro experiments, CD4+ and CD8+ T cells from 17 non-smokers were evaluated for RANKL expression following dose-dependent culture with cigarette smoke extract (CSE) for 5 days. The frequencies of RANKL-positive CD4+ and CD8+ T cells were higher in the patients with COPD than in the non-smokers (P=0.001 and P=0.002, respectively). The proportion of CD4+ T cells positive for both RANKL and interleukin-17 (IL-17) was higher in the patients with COPD than in the non-smokers (P=0.010). However, the frequency of RANKL-expressing Th17 cells was similar among all groups (P=0.508). The frequency of RANKL+CD4+ T cells inversely correlated with BMD of the lumbar vertebrae (P=0.01, r=-0.229), and that of the femoral neck (P<0.001, r=-0.350). The results of our in vitro experiments revealed that CSE increased RANKL expression in CD4+ T cells only. The percentages of RANKL-positive CD4+ T cells and RANKL- and IL-17 double positive CD4+ T cells were increased in the peripheral blood of patients with COPD, and the former were associated with BMD. These observations suggest that RANKL+CD4+ T cells may be mechanistically linked to diseases of the lung and bone in patients with COPD. PMID- 27279358 TI - Does maternal obesity impact pregnancy-related deaths? Michigan experience. AB - Obesity is a multifactorial non-communicable condition that has become a public health epidemic worldwide. The Fifth Millennium Development Goal established the goal of a 75% reduction in the maternal mortality ratio (MMR) between 1990 and 2015. Maternal mortality has been difficult to track over time. Obesity affects pregnancy in more than 50% of women of reproductive age in the state of Michigan; the potential impact of maternal obesity and pregnancy-related deaths (PRDs) has not been studied in Michigan. We conducted a secondary analysis of maternal death cases originally reviewed by the Michigan Maternal Mortality Review Committee from 2004 to 2006 seeking to evaluate the impact of maternal obesity on PRD. Two hundred and five maternal deaths occurred during the period of the study, 61 were classified as PRD. The observed occurrence of PRDs in the obese population was 36 cases while in the non-obese was 25 cases. The study showed a 3.7* risk of PRD in the obese parturient. PMID- 27279359 TI - Saccharide-induced modulation of photoluminescence lifetime in microgels. AB - Sugar-responsive microgels were prepared by the covalent grafting of a poly(N isopropylacrylamide) (pNIPAM) matrix with phenylboronic acid (PBA) as a saccharide sensing unit and a [Ru(bpy)3](2+) derivative (2,2'-bipyridine) as a luminescent reporter. Time-resolved emission studies reveal that the ruthenium complex has an unusually long lifetime (1.6 MUs) and high quantum yield (~0.17) in the PBA-microgel environment. In the presence of sugars, the microgels swell due to the formation of a sugar-boronate ester, leading to a more hydrophilic polymer chain. The swelling is accompanied by a decrease of the lifetime and the photoluminescence quantum yield, which cannot be explained solely by the swelling of the hydrogel. The emission properties of the ruthenium complex in PBA functionalized microgels are compared to those in pNIPAM microgels lacking PBA moieties in various swelling states. The presence of PBA in the vicinity of [Ru(bpy)3](2+) is shown to have a predominant impact on its luminescence properties, mainly through a decrease of the polarity. Sugar-induced triggering of the boronate state thus leads to strong variations of the polarity and the luminescence characteristics. PMID- 27279357 TI - Assessing the criterion validity of four highly abbreviated measures from the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS). AB - OBJECTIVE: Cognitive dysfunction is prevalent in multiple sclerosis. As self reported cognitive functioning is unreliable, brief objective screening measures are needed. Utilizing widely used full-length neuropsychological tests, this study aimed to establish the criterion validity of highly abbreviated versions of the Brief Visuospatial Memory Test - Revised (BVMT-R), Symbol Digit Modalities Test (SDMT), Delis-Kaplan Executive Function System (D-KEFS) Sorting Test, and Controlled Oral Word Association Test (COWAT) in order to begin developing an MS specific screening battery. METHOD: Participants from Holy Name Medical Center and the Kessler Foundation were administered one or more of these four measures. Using test-specific criterion to identify impairment at both -1.5 and -2.0 SD, receiver-operating-characteristic (ROC) analyses of BVMT-R Trial 1, Trial 2, and Trial 1 + 2 raw data (N = 286) were run to calculate the classification accuracy of the abbreviated version, as well as the sensitivity and specificity. The same methods were used for SDMT 30-s and 60-s (N = 321), D-KEFS Sorting Free Card Sort 1 (N = 120), and COWAT letters F and A (N = 298). RESULTS: Using these definitions of impairment, each analysis yielded high classification accuracy (89.3 to 94.3%). CONCLUSIONS: BVMT-R Trial 1, SDMT 30-s, D-KEFS Free Card Sort 1, and COWAT F possess good criterion validity in detecting impairment on their respective overall measure, capturing much of the same information as the full version. Along with the first two trials of the California Verbal Learning Test - Second Edition (CVLT-II), these five highly abbreviated measures may be used to develop a brief screening battery. PMID- 27279360 TI - ICRP Publication 132: Radiological Protection from Cosmic Radiation in Aviation. AB - Abstract -: In this publication, the International Commission on RadiologicalProtection (ICRP) provides updated guidance on radiological protection fromcosmic radiation in aviation, taking into account the current ICRP system of radiologicalprotection, the latest available data on exposures in aviation, and experiencegained worldwide in the management of exposures in aviation. The publicationdescribes the origins of cosmic radiation, how it exposes passengers and aircraftcrew, the basic radiological protection principles that apply to this existing exposuresituation, and the available protective actions. For implementation of the optimisationprinciple, the Commission recommends a graded approach proportionate to thelevel of exposure that may be received by individuals. The objective is to keep theexposure of the most exposed individuals to a reasonable level. The Commission alsorecommends that information be disseminated to raise awareness about cosmic radiation,and to support informed decisions among concerned stakeholders. PMID- 27279361 TI - The epithelial-mesenchymal transition (EMT) is regulated by oncoviruses in cancer. AB - The epithelial-mesenchymal transition (EMT), defined as transdifferentiation of epithelial cells into mesenchymal cells, is critical for embryonic development, wound healing, tissue regeneration, organ fibrosis, and cancer progression. Recently, the role of EMT in carcinogenesis has attracted much attention. Oncoviruses, including human papillomaviruses (HPVs), Epstein-Barr virus (EBV), and hepatitis B and C viruses (HBVs, HCVs), are known to be involved in the etiology of cancer and have been found to play important roles in cancer metastasis, especially in the EMT process. The HPV encoded oncoproteins E6 and E7 (E6/E7), EBV latent membrane protein-1 and -2A, EBV nuclear antigen, HBV-encoded X antigen, and nonstructural HCV protein 5A are all involved in the regulation of EMT. This review primarily focuses on the role of oncoviruses and their encoded proteins or signaling pathways in the EMT process. Understanding their roles will help us in the development of effective strategies for prevention and treatment of virus-related cancers.-Chen, X., Bode, A. M., Dong, Z., Cao, Y. The epithelial mesenchymal transition (EMT) is regulated by oncoviruses in cancer. PMID- 27279362 TI - Epigenetic regulation of soluble guanylate cyclase (sGC) beta1 in breast cancer cells. AB - Soluble guanylate cyclase (sGC) is a heterodimer composed of alpha and beta subunits. The loss of sGCbeta1 has been implicated in several vascular and nonvascular diseases. Our analysis showed that higher levels of sGCbeta1 in breast cancer tissues are correlated with greater survival probability than lower sGCbeta1 levels. However, there is no information on sGC regulation by epigenetic mechanisms. We examined the role of histone deacetylase (HDAC) inhibitors in regulating sGCalpha1 and -beta1 expression in human breast cancer MDA-MB-231 and MDA-MB-468 cell lines. The class I HDAC inhibitors increased the expression of sGCbeta1 more than sGCalpha1. Transient overexpression of HDAC3, but not HDAC1 or HDAC2, significantly reduced sGCbeta1 mRNA. Chromatin immunoprecipitation assay confirmed an enhanced binding of HDAC3 to the sGCbeta1 proximal promoter, which could be reversed by panobinostat (LBH-589) treatment. Mutations at the CCAAT binding sequence, a major element regulating sGCbeta1 expression, markedly reduced the efficacy of LBH-589 in augmenting sGCbeta1 promoter activity. LBH-589 markedly enhanced the binding of nuclear transcription factor Y, subunit alpha, to the sGCbeta1 promoter (CCAAT binding sequence). In summary, HDAC3 is an endogenous antagonist of sGCbeta1 expression. Inhibition of HDAC3 with targeted therapy could benefit treatment of the diseases associated with sGCbeta1 down regulation and/or deficiency such as cancer and several vascular-related diseases.-Sotolongo, A., Monica, F. Z., Kots, A., Xiao, H., Liu, J., Seto, E., Bian, K., Murad, F. Epigenetic regulation of soluble guanylate cyclase (sGC) beta1 in breast cancer cells. PMID- 27279364 TI - High-efficiency sample preparation approach to determine acrylamide levels in high-fat foods. AB - An improved sample preparation method was developed to enhance acrylamide recovery in high-fat foods. Prior to concentration, distilled deionized water was added to protect acrylamide from degradation, resulting in a higher acrylamide recovery rate from fried potato chips. A Chrome-Matrix C18 column (2.6 MUm, 2.1 * 100 mm) was used for the first time to analyze acrylamide levels using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry, displaying good separation of acrylamide from interference. A solid-phase extraction procedure was avoided, and an average recovery of >89.00% was achieved from different food matrices for three different acrylamide spiking levels. Good reproducibility was observed, with an intraday relative standard deviation of 0.04-2.38%, and an interday relative standard deviation of 2.34 3.26%. Thus, combining the improved sample preparation method for acrylamide analysis with the separation on a Chrome-Matrix C18 column (2.6 MUm, 2.1 * 100 mm) using ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry is highly useful for analyzing acrylamide levels in complex food matrices. PMID- 27279363 TI - Cytochrome bd Displays Significant Quinol Peroxidase Activity. AB - Cytochrome bd is a prokaryotic terminal oxidase that catalyses the electrogenic reduction of oxygen to water using ubiquinol as electron donor. Cytochrome bd is a tri-haem integral membrane enzyme carrying a low-spin haem b558, and two high spin haems: b595 and d. Here we show that besides its oxidase activity, cytochrome bd from Escherichia coli is a genuine quinol peroxidase (QPO) that reduces hydrogen peroxide to water. The highly active and pure enzyme preparation used in this study did not display the catalase activity recently reported for E. coli cytochrome bd. To our knowledge, cytochrome bd is the first membrane-bound quinol peroxidase detected in E. coli. The observation that cytochrome bd is a quinol peroxidase, can provide a biochemical basis for its role in detoxification of hydrogen peroxide and may explain the frequent findings reported in the literature that indicate increased sensitivity to hydrogen peroxide and decreased virulence in mutants that lack the enzyme. PMID- 27279365 TI - Research of combined adsorption-coagulation process in treating petroleum refinery effluent. AB - The petroleum refinery industry generates a significant amount of wastewater that contains a high level of organic matter, which calls for effective and costly treatments. In this research, the effectiveness of the petroleum refinery effluent (PRE) treatment with physicochemical process of combined adsorption and coagulation was evaluated. The effects of initial pH, hydraulic condition , and combined sequence of treatment process, different treating reagent types and dosages on the chemical oxygen demand (COD) removal were investigated. Additionally, the elimination efficiency of pollutant wastewater was monitored by gas chromatography-mass spectrometry (GC-MS), and Fourier transformed infrared (FT-IR) spectrophotometer was adopted to describe the structure of the wastewater. Wooden activated carbon was chosen as adsorbent at the dosage of 10 g/L as a primary treatment, and 1500 mg/L polymeric magnesium ferric sulfate was used in coagulation. Results showed that adsorption and subsequent coagulation displayed the best performance when initial pH was 9 at shear rates (G) of G1 = 65 s-1 and G2 = 20 s-1, which reached maximal removal rate of COD and total organic carbon GC-MS testing result revealed that adsorption was effective in phenols and iso-alkanes removal, whereas coagulation was good at removing esters and n-alkanes. PMID- 27279367 TI - Interdisciplinary and innovative : Invitation to the annual conference of the German Society of Neuroradiology and the annual conference of the Austrian Society of Neuroradiology. PMID- 27279366 TI - Establishing Virulence Associated Polyphosphate Kinase 2 as a drug target for Mycobacterium tuberculosis. AB - Inorganic polyphosphate (PolyP) plays an essential role in microbial stress adaptation, virulence and drug tolerance. The genome of Mycobacterium tuberculosis encodes for two polyphosphate kinases (PPK-1, Rv2984 and PPK-2, Rv3232c) and polyphosphatases (ppx-1, Rv0496 and ppx-2, Rv1026) for maintenance of intracellular PolyP levels. Microbial polyphosphate kinases constitute a molecular mechanism, whereby microorganisms utilize PolyP as phosphate donor for synthesis of ATP. In the present study we have constructed ppk-2 mutant strain of M. tuberculosis and demonstrate that PPK-2 enzyme contributes to its ability to cause disease in guinea pigs. We observed that ppk-2 mutant strain infected guinea pigs had significantly reduced bacterial loads and tissue pathology in comparison to wild type infected guinea pigs at later stages of infection. We also report that in comparison to the wild type strain, ppk-2 mutant strain was more tolerant to isoniazid and impaired for survival in THP-1 macrophages. In the present study we have standardized a luciferase based assay system to identify chemical scaffolds that are non-cytotoxic and inhibit M. tuberculosis PPK-2 enzyme. To the best of our knowledge this is the first study demonstrating feasibility of high throughput screening to obtain small molecule PPK-2 inhibitors. PMID- 27279368 TI - Logistical challenges and design considerations for studies using acute anterior cruciate ligament injury as a potential model for early posttraumatic osteoarthritis. AB - Anterior cruciate ligament (ACL) injuries are common and lead to posttraumatic osteoarthritis (PTOA) in a high percentage of patients. Research has been ineffective in identifying successful treatment options for people suffering from symptomatic PTOA resulting in a shift of focus toward the young, ACL injured patients at risk of developing PTOA. Randomized clinical trials examining the very early phase after ACL injury are ideal to study this population; however, these trials face significant challenges regarding recruitment as well as reproducibility of patient-reported outcomes (PROs) and inflammatory and/or chondrodegenerative biomarkers associated with early PTOA. The aim of this work was to develop an approach to allow for early recruitment into an RCT for early treatment following ACL injury and to analyze the variability of commonly used measures and biomarkers at various time points after injury. This paper reports the study design and data related to the first month of treatment for the placebo group of an ongoing 2-year clinical trial to evaluate the effect of an early intra-articular intervention after ACL injury. The results of this study suggest that acute ACL injury results in early changes of both inflammatory and chondrodegenerative biomarkers. These results also provide vital information for researchers to consider when developing future protocols, both related to the logistics of early patient enrollment as well as the appropriate timing of biomarker and patient-reported outcome collection. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:641-650, 2017. PMID- 27279369 TI - Contribution of the Twin Arginine Translocation system to the exoproteome of Pseudomonas aeruginosa. AB - The opportunistic pathogen Pseudomonas aeruginosa uses secretion systems to deliver exoproteins into the environment. These exoproteins contribute to bacterial survival, adaptation, and virulence. The Twin arginine translocation (Tat) export system enables the export of folded proteins into the periplasm, some of which can then be further secreted outside the cell. However, the full range of proteins that are conveyed by Tat is unknown, despite the importance of Tat for the adaptability and full virulence of P. aeruginosa. In this work, we explored the P. aeruginosa Tat-dependent exoproteome under phosphate starvation by two-dimensional gel analysis. We identified the major secreted proteins and new Tat-dependent exoproteins. These exoproteins were further analyzed by a combination of in silico analysis, regulation studies, and protein localization. Altogether we reveal that the absence of the Tat system significantly affects the composition of the exoproteome by impairing protein export and affecting gene expression. Notably we discovered three new Tat exoproteins and one novel type II secretion substrate. Our data also allowed the identification of two new start codons highlighting the importance of protein annotation for subcellular predictions. The new exoproteins that we identify may play a significant role in P. aeruginosa pathogenesis, host interaction and niche adaptation. PMID- 27279370 TI - HDAC3 Is Required for the Downregulation of RORgammat during Thymocyte Positive Selection. AB - To generate functional peripheral T cells, proper gene regulation during T cell development is critical. In this study, we found that histone deacetylase (HDAC) 3 is required for T cell development. T cell development in CD2-icre HDAC3 conditional knockout (cKO) mice (HDAC3-cKO) was blocked at positive selection, resulting in few CD4 and CD8 T cells, and it could not be rescued by a TCR transgene. These single-positive thymocytes failed to upregulate Bcl-2, leading to increased apoptosis. HDAC3-cKO mice failed to downregulate retinoic acid related orphan receptor (ROR) gammat during positive selection, similar to the block in positive selection in RORgammat transgenic mice. In the absence of HDAC3, the RORC promoter was hyperacetylated. In the periphery, the few CD4 T cells present were skewed toward RORgammat(+) IL-17-producing Th17 cells, leading to inflammatory bowel disease. Positive selection of CD8 single-positive thymocytes was restored in RORgammat-KO Bcl-xL transgenic HDAC3-cKO mice, demonstrating that HDAC3 is required at positive selection to downregulate RORgammat. PMID- 27279371 TI - Involvement of PARK2-Mediated Mitophagy in Idiopathic Pulmonary Fibrosis Pathogenesis. AB - Fibroblastic foci, known to be the leading edge of fibrosis development in idiopathic pulmonary fibrosis (IPF), are composed of fibrogenic myofibroblasts. Autophagy has been implicated in the regulation of myofibroblast differentiation. Insufficient mitophagy, the mitochondria-selective autophagy, results in increased reactive oxygen species, which may modulate cell signaling pathways for myofibroblast differentiation. Therefore, we sought to investigate the regulatory role of mitophagy in myofibroblast differentiation as a part of IPF pathogenesis. Lung fibroblasts were used in in vitro experiments. Immunohistochemical evaluation in IPF lung tissues was performed. PARK2 was examined as a target molecule for mitophagy regulation, and a PARK2 knockout mouse was employed in a bleomycin-induced lung fibrosis model. We demonstrated that PARK2 knockdown mediated mitophagy inhibition was involved in the mechanism for activation of the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT signaling pathway accompanied by enhanced myofibroblast differentiation and proliferation, which were clearly inhibited by treatment with both antioxidants and AG1296, a PDGFR inhibitor. Mitophagy inhibition-mediated activation of PDGFR signaling was responsible for further autophagy suppression, suggesting the existence of a self amplifying loop of mitophagy inhibition and PDGFR activation. IPF lung demonstrated reduced PARK2 with concomitantly increased PDGFR phosphorylation. Furthermore, bleomycin-induced lung fibrosis was enhanced in PARK2 knockout mice and subsequently inhibited by AG1296. These findings suggest that insufficient mitophagy-mediated PDGFR/PI3K/AKT activation, which is mainly attributed to reduced PARK2 expression, is a potent underlying mechanism for myofibroblast differentiation and proliferation in fibroblastic foci formation during IPF pathogenesis. PMID- 27279373 TI - FHR3 Blocks C3d-Mediated Coactivation of Human B Cells. AB - The autoimmune renal disease deficient for complement factor H-related (CFHR) genes and autoantibody-positive form of hemolytic uremic syndrome is characterized by the presence of autoantibodies specific for the central complement regulator, factor H, combined with a homozygous deficiency, mostly in CFHR3 and CFHR1 Because FHR3 and FHR1 bind to C3d and inactivated C3b, which are ligands for complement receptor type 2 (CR2/CD21), the aim of the current study was to examine whether FHR3-C3d or FHR1-C3d complexes modulate B cell activation. Laser-scanning microscopy and automated image-based analysis showed that FHR3, but not FHR1 or factor H, blocked B cell activation by the BCR coreceptor complex (CD19/CD21/CD81). FHR3 bound to C3d, thereby inhibiting the interaction between C3d and CD21 and preventing colocalization of the coreceptor complex with the BCR. FHR3 neutralized the adjuvant effect of C3d on B cells, as shown by inhibited intracellular CD19 and Akt phosphorylation in Raji cells, as well as Ca(2+) release in peripheral B cells. In cases of CFHR3/CFHR1 deficiency, the FHR3 binding sites on C3d are occupied by factor H, which lacks B cell-inhibitory functions. These data provide evidence that FHR3, which is absent in patients with the autoimmune form of hemolytic uremic syndrome, is involved in B cell regulation. PMID- 27279372 TI - Autoantibody-Mediated Pulmonary Alveolar Proteinosis in Rasgrp1-Deficient Mice. AB - Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome caused by the accumulation of surfactants in the alveoli. The most prevalent clinical form of PAP is autoimmune PAP (aPAP) whereby IgG autoantibodies neutralize GM-CSF. GM-CSF is a pleiotropic cytokine that promotes the differentiation, survival, and activation of alveolar macrophages, the cells responsible for surfactant degradation. IgG-mediated neutralization of GM-CSF thereby inhibits alveolar macrophage homeostasis and function, leading to surfactant accumulation and innate immunodeficiency. Importantly, there are no rodent models for this disease; therefore, underlying immune mechanisms regulating GM-CSF-specific IgG in aPAP are not well understood. In this article, we identify that autoimmune prone Rasgrp1-deficient mice develop aPAP: 1) Rasgrp1-deficient mice exhibit reduced pulmonary compliance and lung histopathology characteristic of PAP; 2) alveolar macrophages from Rasgrp1-deficient mice are enlarged and exhibit reduced surfactant degradation; 3) the concentration of GM-CSF-specific IgG is elevated in both serum and bronchoalveolar lavage fluid from Rasgrp1-deficient mice; 4) GM CSF-specific IgG is capable of neutralizing GM-CSF bioactivity; and 5) Rasgrp1 deficient mice also lacking CD275/ICOSL, a molecule necessary for conventional T cell-dependent Ab production, have reduced GM-CSF-specific autoantibody and do not develop PAP. Collectively, these studies reveal that Rasgrp1-deficient mice, to our knowledge, represent the first rodent model for aPAP. PMID- 27279375 TI - Improvement in the biological standard of living in 20th century Korea: Evidence from age at menarche. AB - OBJECTIVES: We used age at menarche to understand improvement in the biological standard of living in South Korea during the 20th century. METHODS: The main dataset, the Korean National Health and Nutrition Examination Survey, provided a consistent source of nationally representative data with a large number of observations over a long period of time. We calculated mean ages at menarche by birth year and estimated the rate of decrease in age at menarche, while avoiding survival bias. RESULTS: The mean age at menarche decreased from 16.64 for the birth year 1941 to 12.68 for the birth year 1992, decreasing 0.78 (or 0.81 in a regression) years per decade for the period. Comparisons with other populations demonstrate that this is the fastest rate of decline ever known. In contrast to other developed countries, the decreasing rate in Korea does not appear to slow. We also compared the trend in age at menarche to that of height and found that the rate of increase in height is also the fastest in history. CONCLUSIONS: Age at menarche is an appropriate index of change in the general standard of living in South Korea over the 20th century. Am. J. Hum. Biol. 29:e22882, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27279374 TI - A Novel R848-Conjugated Inactivated Influenza Virus Vaccine Is Efficacious and Safe in a Neonate Nonhuman Primate Model. AB - Influenza virus infection of neonates poses a major health concern, often resulting in severe disease and hospitalization. At present, vaccines for this at risk population are lacking. Thus, development of an effective vaccine is an urgent need. In this study, we have used an innovative nonhuman primate neonate challenge model to test the efficacy of a novel TLR 7/8 agonist R848-conjugated influenza virus vaccine. The use of the intact virus represents a step forward in conjugate vaccine design because it provides multiple antigenic targets allowing for elicitation of a broad immune response. Our results show that this vaccine induces high-level virus-specific Ab- and cell-mediated responses in neonates that result in increased virus clearance and reduced lung pathology postchallenge compared with the nonadjuvanted virus vaccine. Surprisingly, the addition of a second TLR agonist (flagellin) did not enhance vaccine protection, suggesting that combinations of TLR that provide increased efficacy must be determined empirically. These data support further exploration of this new conjugate influenza vaccine approach as a platform for use in the at-risk neonate population. PMID- 27279376 TI - High-efficiency and air-stable P3HT-based polymer solar cells with a new non fullerene acceptor. AB - Solution-processed organic photovoltaics (OPV) offer the attractive prospect of low-cost, light-weight and environmentally benign solar energy production. The highest efficiency OPV at present use low-bandgap donor polymers, many of which suffer from problems with stability and synthetic scalability. They also rely on fullerene-based acceptors, which themselves have issues with cost, stability and limited spectral absorption. Here we present a new non-fullerene acceptor that has been specifically designed to give improved performance alongside the wide bandgap donor poly(3-hexylthiophene), a polymer with significantly better prospects for commercial OPV due to its relative scalability and stability. Thanks to the well-matched optoelectronic and morphological properties of these materials, efficiencies of 6.4% are achieved which is the highest reported for fullerene-free P3HT devices. In addition, dramatically improved air stability is demonstrated relative to other high-efficiency OPV, showing the excellent potential of this new material combination for future technological applications. PMID- 27279377 TI - [A man who was sick of being sick]. PMID- 27279378 TI - [Assessment of microcirculation in critically ill patients]. AB - Adequate organ supply of oxygen and of nutrients depends on microcirculation. Impaired microcirculation may result in temporary or irreversible loss of function. Therefore, critically ill patients require early diagnosis and therapy of microcirculatory disorders. Besides surrogate parameters of microcirculation like urine production or serum lactate levels, direct visualization became possible with sidestream darkfield intravital microscopy. This technique has been evaluated in clinical studies focusing on early diagnosis and therapy in cardiogenic shock like vasopressors, nitrates, or circulatory assist devices. Further studies evaluating measurements of microcirculation are necessary before a general recommendation for its routine use can be made. PMID- 27279379 TI - [Hemodynamic monitoring in intensive care and emergency medicine : Integration of clinical signs and ultrasound findings]. AB - Hemodynamic monitoring is required in critically ill patients presenting with circulatory shock. Besides the clinical evaluation, noninvasive technologies can be used. Guidelines on volume resuscitation and cardiogenic shock already recommend bedside ultrasound as a diagnostic tool. To differentiate the cause of circulatory shock and monitor the effects of therapies, hemodynamic monitoring is necessary. This review discusses possibilities of the different invasive and noninvasive monitoring tools with a focus on the integration of clinical and sonographic parameters. PMID- 27279381 TI - [Corrigendum] Leptin stimulates ovarian cancer cell growth and inhibits apoptosis by increasing cyclin D1 and Mcl-1 expression via the activation of the MEK/ERK1/2 and PI3K/Akt signaling pathways. AB - Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of Figs. 5 and 8; essentially, the beta-actin control bands in Fig. 8 appeared to be a mirror image of the same control bands shown in Fig. 5A. After having re-examined the data, Fig. 5 was correctly presented as shown in the paper, although the beta-actin blot in Fig. 8 had been inadvertently misplaced as a mirror image of the control data from Fig. 5. Two similar experiments were performed at that time, yielding similar results, and the error with the control data did not affect the second of the experiments. Therefore, we present a corrected version of Fig. 8 containing the alternative data. The findings and conclusions of this paper are still supported by our experimental data, and were not affected by this error. We sincerely apologize for this mistake, and thank the reader of our article who drew this matter to our attention. Furthermore, we regret any inconvenience this mistake has caused. [the original article was published in the International Journal of Oncology 42: 1113-1119, 2013; DOI: 10.3892/ijo.2013.1789]. PMID- 27279382 TI - Watch out for a revival of peginesatide in sports. AB - The erythropoietin-mimetic peptide (EMP) peginesatide belongs to the group of erythropoiesis-stimulating agents (ESAs) that are prohibited when misused in sports. Peginesatide is a synthetic pegylated homodimer of two cyclic 21-amino acid chains. It was approved for the treatment of anaemic patients with chronic kidney disease in the USA in 2012, but recalled in 2013 due to prevalent cases of acute severe anaphylactoid reactions and associated fatalities (0.02%). The drug was considered obsolete for athletes and part of the anti-doping scene lost sight of it. However, recent research indicates that the adverse events were not caused by the drug substance, but by the drug product formulated in multi-use vials. These vials contained comparably high levels of subvisible particles. Phenol was identified as a critical component of the drug formulation, which caused the release of histamine from mast cells. Tricky athletes might consider peginesatide a pharmacologically safe ESA in an appropriate formulation. In addition, other EMPs may get a second wind for therapy including misuse in sports. Therefore, it is very important to proceed in developing electrophoretic, immunological, and mass spectroscopic methods for detecting peginesatide and other EMPs in human urine and blood samples. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27279380 TI - Effectiveness of intensification therapies in Danes with Type 2 diabetes who use basal insulin: a population-based study. AB - AIMS: To examine the usage and real-life effectiveness of intensification therapies in people with Type 2 diabetes treated with basal insulin. METHODS: We used population-based healthcare databases in Denmark during 2000-2012 to identify all individuals with a first basal insulin prescription (with or without oral drugs), and evaluated subsequent intensification therapy with bolus insulin, premixed insulin or glucagon-like peptide-1 (GLP-1) receptor agonists. Poisson regression was used to compute the adjusted relative risks of reaching glycaemic control targets. RESULTS: We included 7034 initiators of basal insulin (median age 64 years, diabetes duration 5.3 years, 84% with oral co-medication and median (interquartile range) pre-insulin HbA1c level 77 (65-92) mmol/mol [9.2% (8.1 10.6%)]. Of these, 3076 (43.7%) received intensification therapy after a median of 11 months: 58.5% with premixed insulin, 29.0% with bolus insulin, 10.6% with GLP-1 receptor agonists, and 1.9% with more than one add-on. Overall, 22% had attained an HbA1c level of < 53 mmol/mol (< 7%) by 3-6 months after intensification, while 38% attained an HbA1c < 58 mmol/mol (< 7.5%). Compared with premixed insulin intensification, attainment of HbA1c < 53 and < 58 mmol/mol was similar with bolus insulin add-on [adjusted relative risk 1.03 (95% CI 0.86 1.24) and 1.02 (95% CI 0.91-1.15), and higher for GLP-1 receptor agonist add-on [adjusted relative risk 1.56 (95% CI 1.27-1.92) and 1.27 (1.10-1.47)]. CONCLUSIONS: Among people with Type 2 diabetes, 22 and 38% reached a target HbA1c < 53 mmol/mol (< 7%) or < 58 mmol/mol (< 7.5%), respectively, after intensification of their basal insulin therapy. Compared with premixed insulin, target attainment was similar with bolus insulin and higher with GLP-1 receptor agonists. PMID- 27279383 TI - Retention of eyeblink conditioning in periweanling and adult rats. AB - Eyeblink conditioning is a well-established model for studying the developmental neurobiology of associative learning and memory, though nothing is known regarding developmental differences in retention between periweanling and adult rats. The present study examined retention of eyeblink conditioning in periweanling (postnatal day 24 at the start of training) and adult rats 1, 7, or 28 days after acquisition. Retention was assessed by (1) a conditional stimulus (CS)-alone test session followed by (2) CS-unconditional stimulus (US) reacquisition tests. Conditional response (CR) levels at acquisition were comparable in most respects between ages, and robust CR levels were present at the start of retention tests for both ages in the 1 day group, with CR percentages at block 1 of reacquisition higher in periweanlings relative to adults. At the 7 day retention test there was a trend toward significance for higher CR percentages at the CS-alone test in adults relative to periweanlings, though there were no age differences at reacquisition testing. When testing occurred 28 days after acquisition, however, periweanlings showed fewer CRs relative to adults during reacquisition despite low CR levels in both ages throughout the CS-alone test. Furthermore, periweanlings in the 28 day group required more trials at reacquisition than all other groups to exceed CR levels from their first acquisition session. These findings are consistent with rapid forgetting in the young commonly referred to as "infantile amnesia." The well characterized eyeblink preparation may be useful for future studies investigating neural mechanisms responsible for rapid forgetting in developing animals. PMID- 27279384 TI - Reliability and validity of the Spanish version of the Children's Sleep Habits Questionnaire (CSHQ-SP) in school-age children. AB - BACKGROUND: Sleep disorders in schoolchildren are a common problem worldwide, and when are not adequately diagnosed and treated, their negative impact on daytime functioning may be significant. The aim of this study was to evaluate the psychometric properties of the Spanish version of the Children's Sleep Habits Questionnaire (CSHQ). METHODS: Participants were 286 school-aged children from a community-based sample, aged 4 to 7 years. The sleep behaviour was evaluated using the CSHQ and actigraphy (ActiSleep monitor). The CSHQ was adapted to the Spanish language. The internal consistency of the questionnaire and the test retest reliability between scores at baseline and three-weeks-later were estimated. Associations between CSHQ items and accelerometer sleep quality indicators were used as indicators of concurrent validity. RESULTS: Cronbach's alpha coefficients for the subscales ranged from 0.60 to 0.81, and 0.81 for the full scale; the intraclass correlation coefficients ranged from 0.56 to 0.81. A moderate correlation was observed in sleep latency and awakenings measurements using both parents' reported sleep habits (CSHQ-SP) and sleep quality indicators (ActiSleep). CONCLUSIONS: The CSHQ-SP has demonstrated adequate psychometric properties, and it serves as a useful instrument for clinical and research setting. PMID- 27279385 TI - Nd:YAG laser radiation (1.064 nm) accelerates differentiation of osteoblasts to osteocytes on smooth and rough titanium surfaces in vitro. AB - BACKGROUND: A number of studies revealed beneficial effects of low-level laser therapy (LLLT) regarding cell proliferation and differentiation. AIM: To investigate the effect of Nd:YAG (1.064 nm) laser radiation in the proliferation and differentiation potential of MG-63 osteoblast-like cells. Additionally, the effects of the surface configurations were to be evaluated. MATERIAL AND METHODS: MG-63 osteoblast cells were cultured on different surfaces: plastic tissue culture, smooth (polished) titanium-PT and rough titanium-SLA. The effects of both titanium surfaces and low-level laser therapy (LLLT) on cell adhesion were evaluated by the gene expression of molecules involved in cell proliferation and differentiation. In addition, scanning electron microscopy (SEM) and MTT proliferation assays were used to examine cell morphology and proliferation, respectively. RESULTS: Compared to smooth (PT) surfaces, SLA surfaces favoured MG 63 cell differentiation. Following the application of Nd:YAG laser irradiation, cells yielded statistically significantly improved differentiation on both smooth and SLA surfaces compared with non-irradiated surfaces. CONCLUSIONS: The findings of this present study suggest that both surface morphology and Nd:YAG laser irradiation influence the proliferation and differentiation potential of MG-63 cells. PMID- 27279386 TI - An evaluation of toy quality for increasing self-control in typically developing preschool children. AB - Children often make impulsive choices, and previous research has shown that access to activities during the delay may enhance self-control (e.g., Newquist, Dozier, & Neidert, 2012). The purpose of the current study was to extend the results of Newquist et al. (2012) by comparing the effects of access to low preference, moderate-preference, and high-preference toys during delays. Results showed that (a) all toys increased self-control for 2 participants when toys were available for all choice options and (b) high-preference toys (and sometimes moderate-preference toys) increased self-control for 3 participants when the toys were available only for large delayed choices. PMID- 27279387 TI - Intensive Interaction Training for Paid Carers: 'Looking, Looking and Find Out When They Want to Relate to You'. AB - BACKGROUND: Intensive interaction (II) is a communication approach useful for working with people with severe intellectual disabilities. Health and social care providers offer II training courses to paid carers working in local services with the goal of improving social communication for their clients. MATERIALS AND METHODS: Eight paid carers who had been trained in II were interviewed 2-3 years after training, to explore how their practice had changed, and whether any changes were sustainable. Interviews were analysed using interpretative phenomenological analysis. RESULTS: Analysis revealed a master theme of emotional and practical endurance, with empowerment, better understanding and perceived barriers to implementation comprising subthemes. CONCLUSIONS: Despite actual and perceived barriers to the enduring use of II, all participants spoke positively of the approach and were continuing to use II in practice. PMID- 27279388 TI - Dystrophin Threshold Level Necessary for Normalization of Neuronal Nitric Oxide Synthase, Inducible Nitric Oxide Synthase, and Ryanodine Receptor-Calcium Release Channel Type 1 Nitrosylation in Golden Retriever Muscular Dystrophy Dystrophinopathy. AB - At present, the clinically most advanced strategy to treat Duchenne muscular dystrophy (DMD) is the exon-skipping strategy. Whereas antisense oligonucleotide based clinical trials are underway for DMD, it is essential to determine the dystrophin restoration threshold needed to ensure improvement of muscle physiology at the molecular level. A preclinical trial has been conducted in golden retriever muscular dystrophy (GRMD) dogs treated in a forelimb by locoregional delivery of rAAV8-U7snRNA to promote exon skipping on the canine dystrophin messenger. Here, we exploited rAAV8-U7snRNA-transduced GRMD muscle samples, well characterized for their percentage of dystrophin-positive fibers, with the aim of defining the threshold of dystrophin rescue necessary for normalization of the status of neuronal nitric oxide synthase mu (nNOSMU), inducible nitric oxide synthase (iNOS), and ryanodine receptor-calcium release channel type 1 (RyR1), crucial actors for efficient contractile function. Results showed that restoration of dystrophin in 40% of muscle fibers is needed to decrease abnormal cytosolic nNOSMU expression and to reduce overexpression of iNOS, these two parameters leading to a reduction in the NO level in the muscle fibers. Furthermore, the same percentage of dystrophin-positive fibers of 40% was associated with the normalization of RyR1 nitrosylation status and with stabilization of the RyR1-calstabin1 complex that is required to facilitate coupled gating. We concluded that a minimal threshold of 40% of dystrophin positive fibers is necessary for the reinstatement of central proteins needed for proper muscle contractile function, and thus identified a rate of dystrophin expression significantly improving, at the molecular level, the dystrophic muscle physiology. PMID- 27279389 TI - Oncologic value of laparoscopy-assisted distal gastrectomy for advanced gastric cancer: A systematic review and meta-analysis. AB - BACKGROUND: The oncologic validity of laparoscopic-assisted distal gastrectomy (LADG) in the treatment of advanced gastric cancer (AGC) remains controversial. This study is a systematic review and meta-analysis of the available evidence. MATERIALS AND METHODS: A comprehensive search was performed between 2008 and 2014 to identify comparative studies evaluating morbidity/mortality, oncologic surgery related outcomes, recurrence and survival rates. Data synthesis and statistical analysis were carried out using RevMan 5.2 software. RESULTS: Eight studies with a total of 1456 patients were included in this analysis. The complication rate was lower in LADG [odds ratio (OR) 0.59; 95% confidence interval (CI) = 0.42 0.83; P < 0.002]. The in-hospital mortality rate was comparable (OR 1.22; 95% CI = 0.28-5-29, P = 0.79). There was no significant difference in the number of harvested lymph nodes, resection margins, cancer recurrence rate, cancer-related mortality or overall and disease-free survival (OS and DFS, respectively) rates between the laparoscopic and the open groups (P > 0.05). CONCLUSION: The current study supports the view that LADG for AGC is a feasible, safe and effective procedure in selected patients. Adequate lymphadenectomy, resection margins, recurrence, cancer-related mortality and long-term outcomes appear equivalent to open distal gastrectomy (ODG). PMID- 27279390 TI - Fast-track rehabilitation following video-assisted pulmonary sublobar wedge resection: A prospective randomized study. AB - BACKGROUND: Postoperative morbidity and inhospital length of stay are considered major determinants of total health care expenditure associated with thoracic operations. The aim of this study was to prospectively evaluate the role of video assisted thoracic surgery (VATS) compared to mini-muscle-sparing thoracotomy in facilitating early recovery and hospital discharge after pulmonary sublobar wedge resections. PATIENTS AND METHODS: A total number of 120 patients undergoing elective pulmonary sublobar wedge resection were randomly assigned to VATS (n = 60) or mini-muscle-sparing thoracotomy (n = 60). The primary endpoint was time to hospital discharge. Postoperative complications, cardiopulmonary morbidity and 30 day mortality served as secondary endpoints. RESULTS: Patients' baseline demographic and clinical data did not differ among study arms as well as the number of pulmonary segments resected and the morphology of the nodular lesions. Total hospital stay was significantly shorter in patients assigned to the thoracoscopic technique as opposed to those who were operated using the mini muscle-sparing thoracotomy approach (4 +/- 0.6 versus 4.4 +/- 0.6 days respectively, P = 0.006). Multivariate analysis revealed that VATS approach was inversely associated with longer inhospital stay whereas the number of resected segments was positively associated with an increased duration of hospitalization. Patients in the VATS group were less likely to develop atelectasis (>=1 lobe) compared to those who underwent thoracotomy (0% versus 6.7% respectively, P = 0.042). Kaplan-Meier analysis revealed similar 30-day mortality rates in both study arms (Log-rank P = 0.560). CONCLUSION: VATS was associated with shorter duration of hospitalization positively affecting the patients' quality of life and satisfaction. Significant suppression of the total cost of recovery after thoracoscopic pulmonary resections is expected. PMID- 27279391 TI - Evaluation of hands-on seminar for reduced port surgery using fresh porcine cadaver model. AB - BACKGROUND: The use of various biological and non-biological simulators is playing an important role in training modern surgeons with laparoscopic skills. However, there have been few reports of the use of a fresh porcine cadaver model for training in laparoscopic surgical skills. The purpose of this study was to report on a surgical training seminar on reduced port surgery using a fresh cadaver porcine model and to assess its feasibility and efficacy. MATERIALS AND METHODS: The hands-on seminar had 10 fresh porcine cadaver models and two dry boxes. Each table was provided with a unique access port and devices used in reduced port surgery. Each group of 2 surgeons spent 30 min at each station, performing different tasks assisted by the instructor. The questionnaire survey was done immediately after the seminar and 8 months after the seminar. RESULTS: All the tasks were completed as planned. Both instructors and participants were highly satisfied with the seminar. There was a concern about the time allocated for the seminar. In the post-seminar survey, the participants felt that the number of reduced port surgeries performed by them had increased. CONCLUSION: The fresh cadaver porcine model requires no special animal facility and can be used for training in laparoscopic procedures. PMID- 27279392 TI - Comparison of weight loss outcomes 1 year after sleeve gastrectomy and Roux-en-Y gastric bypass in patients aged above 50 years. AB - INTRODUCTION: Safe, effective weight loss with resolution of comorbidities has been convincingly demonstrated with bariatric surgery in the aged obese. They, however, lose less weight than younger individuals. It is not known if degree of weight loss is influenced by the choice of bariatric procedure. The aim of this study was to compare the degree of weight loss between laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in patients above the age of 50 years at 1 year after surgery. MATERIALS AND METHODS: A retrospective analysis was performed of all patients more than 50 years of age who underwent LSG or LRYGB between February 2012 and July 2013 with at least 1 year of follow-up. Data evaluated at 1 year included age, sex, weight, body mass index (BMI), mean operative time, percentage of weight loss and excess weight loss, resolution/remission of diabetes, morbidity and mortality. RESULTS: Of a total of 86 patients, 54 underwent LSG and 32 underwent LRYGB. The mean percentage of excess weight loss at the end of 1 year was 60.19 +/- 17.45 % after LSG and 82.76 +/- 34.26 % after LRYGB (P = 0.021). One patient developed a sleeve leak after LSG, and 2 developed iron deficiency anaemia after LRYGB. The remission/improvement in diabetes mellitus and biochemistry was similar. CONCLUSION: LRYGB may offer better results than LSG in terms of weight loss in patients over 50 years of age. PMID- 27279393 TI - Usage of a self-adhesive mesh in TAPP hernia repair: A prospective study based on Herniamed Register. AB - INTRODUCTION: Inguinal hernia repair is one of the most frequently performed surgical procedures worldwide in general surgery. The transabdominal laparoscopic (TAPP) approach in the therapy of inguinal hernia seems to be a suitable alternative to classical open inguinal hernia repair mainly in the hands of an experienced surgeon. TAPP repair offers the possibility of gentle dissection with implantation of the mesh and the possibility of non-invasive fixation of the implanted mesh. MATERIALS AND METHODS: Data analysis encompassed all patients who underwent inguinal hernia surgery at our Surgical Department within the period from July 1, 2012 to September 30, 2014 and who fulfilled the inclusion criteria. The standard surgical technique was used. Data were entered and subsequently analysed on the Herniamed platform. Herniamed is an Internet-based register in German and English, and includes all data of outpatient and hospitalised patients who underwent surgery for some type of hernia. All relevant patient data are collected via Internet. RESULTS: There were 241 patients enrolled in the group and there were 396 inguinal hernias repaired in total. Standard long-term follow up after 12 months was evaluated in 205 patients (85.06%), and in the rest of the patients during the closing of the study, but at least 6 months after operation. The mean follow-up was at 19.69 months. At the 1-year assessment, mild discomfort was reported in the groin in 10 patients (4.88%) [1-3 on the visual analogue scale (VAS)]. Post-operative pain lasting over 12 months in the groin of moderate degree (4-6 VAS) was reported in two cases (0.97%). There was no recurrence and no chronic post-operative pain of severe degree reported. CONCLUSION: Our study demonstrates that laparoscopic inguinal hernia repair using the TAPP technique with the implantation of a self-fixation mesh is fast, effective, reliable and economically advantageous method in experienced hands and, according to our results, reduces the occurrence of post-herniorrhaphy inguinal pain (CPIP) and has a low recurrence rate. PMID- 27279394 TI - Single-incision laparoscopic resection of small bowel tumours: Making it easier for patient and surgeon. AB - BACKGROUND: Patients with small bowel tumours frequently require surgical intervention. Minimally invasive techniques require advanced skills and may not be offered to many patients. We present a laparoscopic single-incision technique that is minimally invasive without requiring intracorporeal anastomosis. MATERIALS AND METHODS: The cases of all patients with laparoscopic small bowel resections performed by one surgeon from 2008 to 2012 were reviewed. A single port technique was introduced after it became available at our institution in 2009. Before that, conventional laparoscopy (LAP) was performed with extension of the periumbilical incision to allow externalisation of the bowel. RESULTS: Totally, 10 patients were identified who underwent laparoscopic resection of small bowel tumours: 9 in the small bowel and 1 in the terminal ileum near the cecum. Three tumours were resected before 2009 using LAP, and 7 were resected using the single-port technique. Median length of stay was 3 days, median follow up was 16.5 months, and no patients had a recurrence. Operative time, post operative complications, hospital length of stay, and narcotic utilisation were similar between the single-port and traditional laparoscopic groups. CONCLUSION: Laparoscopic removal of small bowel tumours with a small, periumbilical trocar incision is both effective and feasible without advanced technical skill. PMID- 27279395 TI - Feasibility of thoracoscopic approach for retrosternal goitre (posterior mediastinal goitre): Personal experiences of 11 cases. AB - INTRODUCTION: Posterior mediastinal goitres constitute of a unique surgical thyroid disorder that requires expert management. Occasionally, they require thoracic approach for the completion of thyroidectomy. In this paper, we describe the feasibility and utility of a novel thoracoscopic approach for such goitres. MATERIALS AND METHODS: This is a retrospective study conducted at a tertiary care endocrine surgery department in South India over a period of 5 years from January 2010 to December 2014. We developed a novel thoracoscopic technique for posterior mediastinal goitres instead of a more morbid thoracotomy or sternotomy. All the clinical, investigative, operative, pathological and follow-up data were collected from our prospectively filled database. Statistical analysis was done with SPSS 15.0 version. Descriptive analysis was done. Operative Technique of Thoracoscopic Thyroidectomy: Single lumen endotracheal tube (SLETT) was used of anaesthetic intubation and general inhalational anaesthesia. Operative decubitus was supine with extension and abduction of the ipsilateral arm. Access to mediastinum was obtained by two working ports in the third and fifth intercostal spaces. Mediastinal extension was dissected thoracoscopically and delivered cervically. RESULTS: Out of 1,446 surgical goitres operated during the study period, 72 (5%) had retrosternal goitre. Also, 27/72 (37.5%) cases had posterior mediastinal extension (PME), out of which 11 cases required thoracic approach. We utilised thoracoscopic technique for these 11 cases. The post-operative course was uneventful with no major morbidity. There was one case of recurrent laryngeal nerve (RLN) injury and hoarseness of voice in the third case. Histopathologies in 10 cases were benign, out of which two had subclinical hyperthyroidism. One case had multifocal papillary microcarcinoma. CONCLUSIONS: We opine that novel thoracoscopic technique is a feasibly optimal approach for posterior mediastinal goitre, especially for benign and non-invasive malignant goitres. PMID- 27279396 TI - Experience of single-incision laparoscopy in children. AB - CONTEXT: Laparoscopic surgery is commonly used for the treatment of many pediatric surgical diseases at our department. Single-incision laparoscopic surgery (SILS) is well-known for its cosmetic benefit. We, hereby, present our experience of SILS and evaluate its efficacy. MATERIALS AND METHODS: From July 2012 to June 2014, 78 patients aged less than 18 years who underwent SILS were retrospectively evaluated. There were 44 males and 34 females, with a mean age of 10.3 years. The procedures included appendectomy (n = 64), reduction of intussusception (n = 8), removal of an intestinal foreign body (n = 3), and Meckel's diverticulectomy (n = 3). We compared the patients who underwent SILS with those who underwent conventional laparoscopic surgery (CLS), regarding these procedures. The parameters for analysis included the patient's demographic data, surgical indication, complications, operative time, and length of hospital stay. CONCLUSION: SILS is comparable to CLS regarding two major procedures, namely, appendectomy and reduction of intussusception. There were no significant differences between the two groups regarding the patients' demographic data, complications, and length of hospital stay. According to our experience of SILS, it could be a feasible and safe procedure for the treatment of various pediatric surgical diseases. However, large prospective randomized studies are needed to identify the differences between SIL and CLS. PMID- 27279397 TI - Use of a multi-instrument access device in abdominoperineal resections. AB - BACKGROUND: Laparoscopic colorectal surgery results in less post-operative pain, faster recovery, shorter length of stay and reduced morbidity compared with open procedures. Less or minimally invasive techniques have been developed to further minimise surgical trauma and to decrease the size and number of incisions. This study describes the safety and feasibility of using an umbilical multi-instrument access (MIA) port (Olympus TriPort+) device with the placement of just one 12-mm suprapubic trocar in laparoscopic (double-port) abdominoperineal resections (APRs) in rectal cancer patients. PATIENTS AND METHODS: The study included 20 patients undergoing double-port APRs for rectal cancer between June 2011 and August 2013. Preoperative data were gathered in a prospective database, and post operative data were collected retrospectively. RESULTS: The 20 patients (30% female) had a median age of 67 years (range 46-80 years), and their median body mass index (BMI) was 26 kg/m2 (range 20-31 kg/m2). An additional third trocar was placed in 2 patients. No laparoscopic procedures were converted to an open procedure. Median operating time was 195 min (range 115-306 min). A radical resection (R0 resection) was achieved in all patients, with a median of 14 lymph nodes harvested. Median length of stay was 8 days (range 5-43 days). CONCLUSION: Laparoscopic APR using a MIA trocar is a feasible and safe procedure. A MIA port might be of benefit as an extra option in the toolbox of the laparoscopic surgeon to further minimise surgical trauma. PMID- 27279398 TI - Gut barrier function and systemic endotoxemia after laparotomy or laparoscopic resection for colon cancer: A prospective randomized study. AB - PURPOSE: The gut barrier is altered in certain pathologic conditions (shock, trauma, or surgical stress), resulting in bacterial and/or endotoxin translocation from the gut lumen into the systemic circulation. In this prospective randomized study, we investigated the effect of surgery on intestinal permeability (IP) and endotoxemia in patients undergoing elective colectomy for colon cancer by comparing the laparoscopic with the open approach. PATIENTS AND METHODS: A hundred twenty-three consecutive patients underwent colectomy for colon cancer: 61 cases were open resection (OR) and 62 cases were laparoscopic resection (LR). IP was measured preoperatively and at days 1 and 3 after surgery. Serial venous blood sample were taken at 0, 30, 60, 90, 120, and 180 min, and at 12, 24, and 48 h after surgery for endotoxin measurement. RESULTS: IP was significantly increased in the open and closed group at day 1 compared with the preoperative level (P < 0.05), but no difference was found between laparoscopic and open surgery group. The concentration endotoxin systemic increased significantly in the both groups during the course of surgery and returned to baseline levels at the second day. No difference was found between laparoscopic and open surgery. A significant correlation was observed between the maximum systemic endotoxin concentration and IP measured at day 1 in the open group and in the laparoscopic group. CONCLUSION: An increase in IP, and systemic endotoxemia were observed during the open and laparoscopic resection for colon cancer, without significant statistically difference between the two groups. PMID- 27279399 TI - Comparative study of postoperative analgesic effect of intraperitoneal instillation of dexmedetomidine with bupivacaine and bupivacaine alone after laparoscopic surgery. AB - AIMS: This prospective double-blinded study was designed with the aim of comparing the analgesic effect of intraperitoneal instillation of dexmedetomidine with bupivacaine with that with bupivacaine alone in patients undergoing laparoscopic surgeries. MATERIALS AND METHODS: A total of 100 patients of either sex undergoing elective laparoscopic surgery were randomly divided into two groups containing 50 patients in each group. Group B received intraperitoneal instillation with 50 mL of bupivacaine 0.25% (125 mg) and groups B + D received 50 mL of bupivacaine 0.25% (125 mg) + 1 MUg/kg of dexmedetomidine. Pain was assessed using visual analogue scale (VAS) at 0.5 h, 1 h, 2 h, 4 h, 6 h, and 24 h after the surgery. The requirement of rescue analgesics were recorded. RESULT: Duration of analgesia was longer in group B+D (14.5 hr) compared to group B (13.06 hr). The requirement of rescue analgesic in 24 hours was less in group B+D (1.76) compared to group B (2.56) which were statistically significant (P < 0.05). The mean number of total rescue analgesia given in 24 h was less in group B+D was 1.76 whereas in group B was 2.56 that were statistically significant. CONCLUSION: Intraperitoneal instillation of dexmedetomidine with bupivacaine prolongs the duration of postoperative analgesia as compared to that with bupivacaine alone. And also there is less number of rescue analgesics that are required postoperatively when dexmedetomidine is supplemented as an adjuvant to bupivacaine. PMID- 27279400 TI - Laparoscopic surgery and polycystic liver disease: Clinicopathological features and new trends in management. AB - BACKGROUND: Polycystic liver disease (PLD) has a low frequency overall in the worldwide population. As the patient's symptoms are produced by the expansion of hepatic volume, the different therapeutic alternatives are focused on reducing it. Surgery is still considered the most effective treatment for symptomatic PLD. The aim of this study was to evaluate the long-term outcomes of laparoscopic surgery for PLD. MATERIALS AND METHODS: This study included 14 patients who were diagnosed with symptomatic PLD and underwent surgery by a laparoscopic approach between 2004 and 2012. It involved collecting data on the characteristics of those patients and their liver disease, surgical procedures, intra- and postoperative complications, and the long-term follow-up. RESULTS: Twelve laparoscopic multiple-cyst fenestrations and two segmentary liver resections associated with remaining-cyst fenestration were performed. One procedure required conversion to laparotomy and the other was complicated by anhepatic severe bleeding. The rest of the procedures were uneventful. One patient developed persistent self-limited ascites in the immediate postoperative period. Symptoms disappeared after surgical intervention in all patients. During a median follow-up of 62 months (range 14-113 months), there were two clinical recurrences and one asymptomatic radiological recurrence. One patient required further surgery. CONCLUSION: Laparoscopic cystic fenestration and laparoscopic liver resection are safe and long-term, effective procedures for the treatment of symptomatic PLD. Severity and morphological characteristics of the hepatic disease will determine the surgical indication and the optimal approach for each patient. PMID- 27279401 TI - Early assessment of bilateral inguinal hernia repair: A comparison between the laparoscopic total extraperitoneal and Stoppa approaches. AB - BACKGROUND: The present clinical trial was designed to compare the results of bilateral inguinal hernia repair between patients who underwent the conventional Stoppa technique and laparoscopic total extraperitoneal repair (LTE) with a single mesh and without staple fixation. PATIENTS AND METHODS: This controlled, randomised clinical trial was conducted at General Surgery and Trauma of the Clinics Hospital, Medical School, the University of Sao Paulo between September 2010 and February 2011. Totally, 50 male patients, with a bilateral inguinal hernia, older than 25 years were considered eligible for the study. The following parameters were analysed during the early post-operative period: (1) The intensity of surgical trauma, operation time, C-reactive protein (CRP) levels, white blood cell count, bleeding and pain intensity; (2) quality of life assessment; and (3) post-operative complications. RESULTS: LTE procedure was longer than the Stoppa procedure (134.6 min +/- 38.3 vs. 90.6 min +/- 41.3; P < 0.05). The levels of CRP were higher in the Stoppa group (P < 0.05) but the number of leucocytes, haematocrit, and haemoglobin were similar between the groups (P > 0.05). There was no difference in pain during the 1st and 7th post operative, physical functioning, physical limitation, the impact of pain on daily activities, and the Carolinas Comfort Scale during the 7th and 15th post operative (P > 0.05). Complications occurred in 88% of Stoppa group (22 patients) and 64% in LTE group (16 patients) (P < 0.05). CONCLUSION: The comparative study between the Stoppa and LTE approaches for the bilateral inguinal hernia repair demonstrated that: (1) The LTE approach showed less surgical trauma despite the longer operation time; (2) Quality of life during the early post-operative period were similar; and (3) Complication rates were higher in the Stoppa group. PMID- 27279402 TI - Laparoscopic management of recurrent pheochromocytoma: A case report. AB - Recurrence of pheochromocytoma after a total adrenalectomy is uncommon. Such recurrent tumours are mostly managed by the open technique, with very few studies reporting laparoscopic management. We hereby report a case of successful laparoscopic management of a recurrent pheochromocytoma after total adrenalectomy for left adrenal pheochromocytoma. PMID- 27279403 TI - Congenital absence of the common bile duct: A rare anomaly of extrahepatic biliary tract. AB - Congenital absence of the common bile duct (CBD) is an extremely rare developmental anomaly with right and left hepatic ducts draining directly into the gallbladder (GB). Other synonyms for this clinical condition are "cholecystohepatic ducts", "transverse lie of the GB" or "interposition of the GB". The potential for iatrogenic injury is high, because of either inadvertent division or ligation of the ducts. Diagnosis is mostly made intraoperatively, and needs some form of biliary reconstruction. Herein, we are reporting a case of congenital absence of the CBD in a 36-year-old lady that was detected intraoperatively. PMID- 27279404 TI - Laparoscopic excision of large lower rectal gastrointestinal stromal tumour (GIST): A case report. AB - Gastrointestinal stromal tumour (GIST) involving rectum is rare. No definite method of treatment has been established because of a small number of cases being reported. It is usually managed with invasive or ablative surgery, such as abdominoperineal resection (APR). The acceptance of minimally invasive (laparoscopic) surgery in colorectal disease plays a pivotal role in improving the postoperative quality of life. We report a case of a large lower rectal GIST who underwent laparoscopic excision of tumour through a subserosal approach whilst preserving the anal sphincter and without any rectal resection. PMID- 27279405 TI - Epidermoid cyst at a rare location, as a content of inguinal hernia: A case report with a review of the literature. AB - Epidermoid cysts can occur in a variety of locations including the face, trunk, neck, extremities, and scalp. No case of epidermoid cyst as content of inguinal hernia has been reported so far; however, cases with dermoid, teratoma, lipoma, lymphangioma and leiomyoma as content of inguinal canal have been reported. A 29 year-old female presented with a lump in the left inguinal region that was clinically diagnosed as left inguinal hernia. The patient was planned for laparoscopic inguinal hernia repair after routine investigation. Intraoperatively, a cystic mass was found to be attached to the left round ligament that was excised completely. Histopathological report was consistent with epidermal inclusion cyst. Inguinal epidermoid cyst mimicking inguinal hernia is a rare entity. If such a cyst is encountered during operation, it should be completely excised. PMID- 27279406 TI - Transanal minimally invasive surgery (TAMIS) approach for large juxta-anal gastrointestinal stromal tumour. AB - Gastrointestinal stromal tumours (GISTs) are rarely found in the rectum. Large rectal GISTs in the narrow pelvis sometimes require extended abdominal surgery to obtain free resection margins, and it is a challenge to preserve sufficient anal sphincter and urogenital function. Here we present a 56-year-old male with a locally advanced juxta-anal non-metastatic GIST of approximately 10 cm in diameter. Therapy with imatinib reduced the tumour size and allowed partial intersphincteric resection (pISR). The patient underwent an electrophysiology controlled nerve-sparing hybrid of laparoscopic and transanal minimally invasive surgery (TAMIS) in a multimodal setting. The down-to-up approach provided sufficient dissection plane visualisation and allowed the confirmed nerve sparing. Lateroterminal coloanal anastomosis was performed. Follow-up showed preserved urogenital function and good anorectal function, and the patient remains disease-free under adjuvant chemotherapy as of 12 months after surgery. This report suggests that the TAMIS approach enables extraluminal high-quality oncological and function-preserving excision of high-risk GISTs. PMID- 27279407 TI - Laparoscopic repair in children with traumatic bladder perforation. AB - Here, we report two patients with a traumatic intraperitoneal bladder dome rupture repaired by laparoscopic intracorporeal sutures. The first patient was a 3-year old boy was admitted with a history of road accident. He had a traumatic lesion on his lower abdomen and a pelvic fracture. Computed tomography (CT) scan revealed free intraabdominal fluid. The urethragram showed spreading contrast material into the abdominal cavity. Laparoscopic exploration revealed a 3-cm length perforation at the top of the bladder. The injury was repaired in a two fold fashion. Post-operative follow-up was uneventful. The second case was a 3 year-old boy fell from the second floor of his house on the ground. He had traumatic lesion on his lower abdomen and a pelvic fracture. Due to bloody urine drainage, a cystography was performed and an extravasation from the dome of the bladder into the peritoneum was detected. On laparoscopy, a 3-cm long vertical perforation at the dome of the bladder was found. The perforation was repaired in two layers with intracorporeal suture technique. The post-operative course was uneventful. Laparoscopic repair of traumatic perforation of the bladder dome is a safe, effective and minimally invasive method. The cosmetic outcome is superior. PMID- 27279408 TI - Retrograde intra-vesical reconstructive surgery (RIVRS): A novel technique. AB - Management of distal ureter by en block resection during radical nephrectomy for upper urinary tract transitional cell carcinoma (TCC) is considered as standard of care. In this report, we describe our technique for management of lower ureter which utilizes both the endoscopic and laparoscopic approach. The nephrectomy including the dissection of the lower ureter was completed laproscopically. The ureteral orifice was scored using a hook passed through a 24 Fr nephroscope and secured .Transurethral suturing of the defect with SewRight SR5 device passed through the working channel of the 24 Fr nephroscope was done. Our report highlights the fact that management of lower ureter in TCC pelvis can be done endoscopically/laproscopically without compromising the oncological principles. Our novel technique demonstrates feasibility of intra mural resection of the ureter and primary closure of the bladder endoscopically. PMID- 27279409 TI - Why have we embraced minimally invasive surgery and ignored enhanced recovery after surgery? AB - There has been a lot of enthusiasm about minimally invasive surgery (MIS) in the surgical community in recent times. Some of the main reasons for this are an unmatched appeal to patients, doctors and healthcare systems alike. Push from the industry also serves as an important reason for its popularity. 'Enhanced recovery after surgery' (ERAS) is a programme of implementing multimodal interventions in the perioperative period to promote faster recovery. Even though MIS is an important component of ERAS protocols, the latter has not seen the reception the former has received. In this article, the authors present their personal viewpoint on the matter. The authors intend to highlight issues surrounding an increasing emphasis on MIS and to caution against the MIS operative technique superseding comprehensive perioperative care. PMID- 27279410 TI - Minimally invasive surgery and enhanced recovery: Are we talking about apples and oranges? PMID- 27279411 TI - Serum markers of pre-eclampsia identified on proteomics. AB - AIM: Pre-eclampsia (PE) is a disorder of pregnancy associated with maternal and fetal mortality and morbidity. The aim of the present study was to use proteomics to identify biomarkers of, and elucidate the pathogenesis of, PE. METHODS: Serum samples were analyzed using peptide ligand library beads (PLLB) on liquid chromatography-mass spectrometry/mass spectrometry. Retinol-binding protein 4 (RBP4) was used as the target protein for further validation on enzyme-linked immunosorbent assay, immunohistochemistry and real-time polymerase chain reaction. Transwell invasion assay was used to evaluate whether RBP4 affects the invasive ability of trophoblast tumor cells. RESULTS: Twenty upregulated and 17 downregulated proteins were differentially expressed between severe PE patients and healthy pregnant women. Those proteins were further classified according to molecular function and biological process according to the gene ontology terms. RBP4 concentration was significantly lower in women with severe PE than in those with healthy pregnancy. CONCLUSIONS: RBP4 is able to function as biomarker to distinguish severe PE from normal pregnancy. More importantly, these results may shed light on the role of RPB4 in the pathogenesis in PE. Further studies are required to validate these results, and determine the precise role of RBP4 in the pathogenesis of PE. PMID- 27279412 TI - Evaluating the role of embolization and carotid artery sacrifice and reconstruction in the management of carotid body tumors. AB - OBJECTIVES/HYPOTHESIS: To review the surgical management of carotid body tumors (CBT), outcomes of carotid artery reconstruction, as well as utility of preoperative embolization. STUDY DESIGN: Retrospective chart review. METHODS: A single-surgeon case series with chart review was performed of all cases between 1997 and 2014 at a single institution. Tumor classification, major neurovascular resection, requirement for in-line carotid artery reconstruction, intraoperative blood loss, and operative time, and postoperative neurovascular complications were determined. RESULTS: In all, 96 patients with 101 CBTs underwent definitive resection disease. Vascular sacrifice was 2.9% (three) for the internal jugular vein, 8.9% (nine) for the external carotid artery, and 13.8% (14) for the internal carotid artery (ICA). ICA sacrifices were performed with immediate in line arterial bypass grafting with vascular surgery. Permanent cranial neuropathies occurred in 4.9% (five) of patients, without cerebrovascular events. CONCLUSIONS: We recommend surgical resection as the primary approach to the management of these CBTs. In lesions involving the ICA, we recommend vein bypass grafting. We found no differences or advantages to preoperative embolization. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2282-2287, 2016. PMID- 27279414 TI - Tiotropium for the treatment of asthma: a drug safety evaluation. AB - INTRODUCTION: Tiotropium, a once-daily long-acting anticholinergic bronchodilator, has recently been approved for use in the treatment of asthma in a number of countries, including the EU and the USA, and was incorporated into the 2015 update of the Global Initiative for Asthma treatment guidelines. Here we review safety data from published clinical trials to help inform the use of tiotropium in the treatment of patients with asthma. AREAS COVERED: Safety data from recently published clinical trials, which compared tiotropium with placebo or an active control, were reviewed. Trials included children, adolescents, and adults across severities of symptomatic asthma, and assessed tiotropium delivered via the Respimat and HandiHaler devices. EXPERT OPINION: Based on the reviewed scientific evidence, tiotropium is a safe and well-tolerated long-acting anticholinergic bronchodilator for use in the treatment of asthma. In the trials assessed, the safety of tiotropium was found to be comparable with that of placebo and alternative therapeutic options, including a doubling in the dose of inhaled corticosteroids and the long-acting beta2-agonist salmeterol. PMID- 27279413 TI - Two endoplasmic reticulum proteins (calnexin and calreticulin) are involved in innate immunity in Chinese mitten crab (Eriocheir sinensis). AB - Calnexin (Cnx) and calreticulin (Crt), which are important chaperones in the endoplasmic reticulum (ER), participate in the folding and quality control of client proteins. Cnx and Crt identified from Chinese mitten crab (Eriocheir sinensis) are designated as EsCnx and EsCrt, respectively. EsCnx and EsCrt are expressed in the hemocyte, hepatopancrea, gill, and intestine at the mRNA and protein level. Immunofluorescence analysis indicated that EsCnx and EsCRT are located in the ER. Moreover, the mRNA and protein expression levels of EsCnx and EsCrt were altered by challenge with lipopolysaccharides (LPS), peptidoglycans (PGN), Staphyloccocus aureus, and Vibrio parahaemolyticus. Recombinant EsCnx and EsCrt (rEsCnx and rEsCrt, respectively) proteins can bind to various Gram positive and Gram-negative bacteria, as well as to different polysaccharides (LPS and PGN). rEsCnx and rEsCrt assisted in the clearance of V. parahaemolyticus in vivo, and the clearance efficiency was impaired after silencing of EsCnx and EsCrt. Our results suggest that the two ER proteins are involved in anti bacterial immunity in E. sinensis. PMID- 27279415 TI - Streptomyces as a plant's best friend? AB - Here we discuss the advantages of the majority of this versatile and diverse group of microorganisms for plant health and growth as demonstrated by their contribution to disease-suppressive soils, their antifungal and antibacterial activities, their ability to produce volatile compounds and their capacity to enhance plant biomass. Although much is still to be discovered about the colonization strategies and molecular interactions between plant roots and these microorganisms, they are destined to become important players in the field of plant growth-promoting rhizobacteria for agriculture. PMID- 27279416 TI - Widespread green algae Chlorella and Stichococcus exhibit polar-temperate and tropical-temperate biogeography. AB - Chlorella and Stichococcus are morphologically simple airborne microalgae, omnipresent in terrestrial and aquatic habitats. The minute cell size and resistance against environmental stress facilitate their long-distance dispersal. However, the actual distribution of Chlorella- and Stichococcus-like species has so far been inferred only from ambiguous morphology-based evidence. Here we contribute a phylogenetic analysis of an expanded SSU and ITS2 rDNA sequence dataset representing Chlorella- and Stichococcus-like species from terrestrial habitats of polar, temperate and tropical regions. We aim to uncover biogeographical patterns at low taxonomic levels. We found that psychrotolerant strains of Chlorella and Stichococcus are closely related with strains originating from the temperate zone. Species closely related to Chlorella vulgaris and Muriella terrestris, and recovered from extreme terrestrial environments of polar regions and hot deserts, are particularly widespread. Stichococcus strains from the temperate zone, with their closest relatives in the tropics, differ from strains with the closest relatives being from the polar regions. Our data suggest that terrestrial Chlorella and Stichococcus might be capable of intercontinental dispersal; however, their actual distributions exhibit biogeographical patterns. PMID- 27279417 TI - Monitoring the impact of bioaugmentation with a PAH-degrading strain on different soil microbiomes using pyrosequencing. AB - The effect of bioaugmentation with Sphingobium sp. AM strain on different soils microbiomes, pristine soil (PS), chronically contaminated soil (IPK) and recently contaminated soil (Phe) and their implications in bioremediation efficiency was studied by focusing on the ecology that drives bacterial communities in response to inoculation. AM strain draft genome codifies genes for metabolism of aromatic and aliphatic hydrocarbons. In Phe, the inoculation improved the elimination of phenanthrene during the whole treatment, whereas in IPK no improvement of degradation of any PAH was observed. Through the pyrosequencing analysis, we observed that inoculation managed to increase the richness and diversity in both contaminated microbiomes, therefore, independently of PAH degradation improvement, we observed clues of inoculant establishment, suggesting it may use other resources to survive. On the other hand, the inoculation did not influence the bacterial community of PS. On both contaminated microbiomes, incubation conditions produced a sharp increase on Actinomycetales and Sphingomonadales orders, while inoculation caused a relative decline of Actinomycetales. Inoculation of most diverse microbiomes, PS and Phe, produced a coupled increase of Sphingomonadales, Burkholderiales and Rhizobiales orders, although it may exist a synergy between those genera; our results suggest that this would not be directly related to PAH degradation. PMID- 27279418 TI - Effects of 17-AAG on the cell cycle and apoptosis of H446 cells and the associated mechanisms. AB - As a heat shock protein 90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17 AAG) has been studied in numerous types of cancer, however the effects of 17-AAG on apoptosis and the cell cycle of H446 cells remain unclear. In the current study, the MTT method was used to evaluate the inhibitory effects of different durations and doses of 17-AAG treatment on the proliferation of H446 cells. The cells were stained with Annexin-fluorescein isothiocyanate/propidium iodide and measured by flow cytometry, and the gene and protein expression levels of signal transducer and activator of transcription 3 (STAT3), survivin, cyclin D1, cyt-C, caspase 9 and caspase 3 were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results indicated that with treatment with 1.25-20 mg/l 17-AAG for 24 and 48 h, significant inhibition of H446 cell proliferation was observed in a time- and dose-dependent manner. With treatment of 3.125, 6.25 and 12.5 mg/l 17-AAG for 48 h, significant apoptosis and cell cycle arrest was observed. The results indicated that the gene and protein expression levels of STAT3, survivin and cyclin D1 were downregulated, and cyt-C, caspase 9 and caspase 3 were upregulated by 17-AAG in a dose-dependent manner when the cells were treated with 3.125 and 6.25 mg/l 17-AAG for 48 h. The results indicated that 17-AAG is able to inhibit the cell proliferation, induce apoptosis and G2/M arrest and downregulate the gene and protein expression levels of STAT3, survivin and cyclin D1, and upregulate gene and protein expression of cyt-C, caspase 9, caspase 3. PMID- 27279419 TI - Iloprost supports early development of in vitro-produced porcine embryos through activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. AB - Despite evidence of the presence of prostaglandin (PG) I2 in mammalian oviducts, its role in early development of in vitro-produced (IVP) embryos is largely unknown. Thus, in the present study we examined the effects of iloprost, a PGI2 analogue, on the in vitro developmental competence of early porcine embryos and the underlying mechanism(s). To examine the effects of iloprost on the development rate of IVF embryos, iloprost was added to the in vitro culture (IVC) medium and cultured for 6 days. Supplementation of the IVC medium with iloprost significantly improved developmental parameters, such as blastocyst formation rate, the trophectoderm:inner cell mass ratio and cell survival in IVF and parthenogenetically activated (PA) embryos. In addition, post-blastulation development into the expanded blastocyst stage was improved in iloprost-treated groups compared with controls. Interestingly, the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway was significantly activated by iloprost supplementation in a concentration-dependent manner (10-1000nM), and the beneficial effects of iloprost on the early development of porcine IVF and PA embryos was completely ablated by treatment with 2.5MUM wortmannin, a PI3K/AKT signalling inhibitor. Importantly, expression of the PI3K/AKT signalling pathway was significantly reduced in somatic cell nuclear transfer (SCNT) compared with IVF embryos, and iloprost supported the early development of SCNT embryos, as was the case for IVF and PA embryos, suggesting a consistent effect of iloprost on the IVC of IVP porcine embryos. Together, these results indicate that iloprost can be a useful IVC supplement for production of IVP early porcine embryos with high developmental competence. PMID- 27279420 TI - Secretory leukocyte protease inhibitor promotes differentiation and mineralization of MC3T3-E1 preosteoblasts on a titanium surface. AB - Mineralized bone matrix constituted with collagenous and non-collagenous proteins was synthesized by osteoblasts differentiated from mesenchymal stem cells. Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, promotes cell migration and proliferation, and suppresses the inflammatory response. Recent studies reported that SLPI regulates the formation of dentin and mineralization by odontoblasts and increases the adhesion and viability of preosteoblasts on a titanium (Ti) surface. Ti and its alloys are widely used implant materials in artificial joints and dental implants owing to their biocompatibility with bone. Therefore, this study aimed to examine whether SLPI can be an effective molecule in promoting differentiation and mineralization of osteoblasts on a Ti surface. In order to investigate the effects of SLPI on osteoblasts, an MTT assay, PCR, western blotting and Alizarin Red S staining were performed. The results demonstrated that SLPI increased the viability of osteoblasts during differentiation on Ti discs compared with that of the control. The expression levels of SLPI mRNA and protein were higher than that of the control after treatment of osteoblasts with SLPI on Ti discs during differentiation. SLPI increased the formation of mineralized nodules and mRNA expression of alkaline phosphatase, dentin sialophosphoprotein, dentin matrix protein 1, bone sialoprotein, and collagen I in osteoblasts on Ti discs compared with that of the control. In conclusion, SLPI increases the viability and promotes the differentiation and mineralization of osteoblasts on Ti surfaces, suggesting that SLPI is an effective molecule for achieving successful osseointegration between osteoblasts and a Ti surface. PMID- 27279421 TI - A Pharmacological Review of Bioactive Constituents of Paeonia lactiflora Pallas and Paeonia veitchii Lynch. AB - The roots of two peony species, Paeonia lactiflora Pallas and Paeonia veitchii Lynch are routinely referred to as either chishao () or baishao (). This paper reviews the botanical origins and traditional medicinal usage of each species, as well as pharmacological like activity of their constituents. A search of herbal pharmacological encyclopaedia, PubChem and PubMed databases identified their known constituents. The biological data for these constituents were evaluated and classified according to pharmacological-like activity, with emphasis on compounds of greatest concentration and bioavailability. It was found that P. lactiflora and P. veitchii have some common compounds; however, their phytochemical bioavailability varies. Furthermore, a larger number of compounds have been identified in P. lactiflora. These have greater potential for antiinflammatory, antiviral, antibacterial and antioxidant therapeutic activity compared with P. veitchii. However, evidence indicates both species are similarly indicated for antiviral and glycaemic activity. Major compounds of each are classified as flavonoids, hydrolysable tannins (polyphenols) and monoterpene glycosides. The evidence suggests both species, when administered in entire botanical form, have an excellent safety profile; however, constituent toxicity risk evidence is limited, requiring further investigation. Although experiments show many compounds have biological activity, further investigation of their therapeutic potential is needed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27279423 TI - Mixed-scale channel networks including Kingfisher-beak-shaped 3D microfunnels for efficient single particle entrapment. AB - Reproducible research results for nanofluidics and their applications require viable fabrication technologies to produce nanochannels integrated with microchannels that can guide fluid flow and analytes into/out of the nanochannels. We present the simple fabrication of mixed-scale polydimethylsiloxane (PDMS) channel networks consisting of nanochannels and microchannels via a single molding process using a monolithic mixed-scale carbon mold. The monolithic carbon mold is fabricated by pyrolyzing a polymer mold patterned by photolithography. During pyrolysis, the polymer mold shrinks by ~90%, which enables nanosized carbon molds to be produced without a complex nanofabrication process. Because of the good adhesion between the polymer mold and the Si substrate, non-uniform volume reduction occurs during pyrolysis resulting in the formation of curved carbon mold side walls. These curved side walls and the relatively low surface energy of the mold provide efficient demolding of the PDMS channel networks. In addition, the trigonal prismatic shape of the polymer is converted into to a Kingfisher-beak-shaped carbon structure due to the non-uniform volume reduction. The transformation of this mold architecture produces a PDMS Kingfisher-beak-shaped 3D microfunnel that connects the microchannel and the nanochannel smoothly. The smooth reduction in the cross sectional area of the 3D microfunnels enables efficient single microparticle trapping at the nanochannel entrance; this is beneficial for studies of cell transfection. PMID- 27279422 TI - TGF-beta in jaw tumor fluids induces RANKL expression in stromal fibroblasts. AB - Odontogenic tumors and cysts, arising in the jawbones, grow by resorption and destruction of the jawbones. However, mechanisms underlying bone resorption by odontogenic tumors/cysts remain unclear. Odontogenic tumors/cysts comprise odontogenic epithelial cells and stromal fibroblasts, which originate from the developing tooth germ. It has been demonstrated that odontogenic epithelial cells of the developing tooth germ induce osteoclastogenesis to prevent the tooth germ from invading the developing bone to maintain its structure in developing bones. Thus, we hypothesized that odontogenic epithelial cells of odontogenic tumors/cysts induce osteoclast formation, which plays potential roles in tumor/cyst outgrowth into the jawbone. The purpose of this study was to examine osteoclastogenesis by cytokines, focusing on transforming growth factor-beta (TGF beta), produced by odontogenic epithelial cells. We observed two pathways for receptor activator of NF-kappaB ligand (RANKL) induction by keratocystic odontogenic tumor fluid: the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway through interleukin-1alpha (IL-1alpha) signaling and non-COX-2/PGE2 pathway through TGF-beta receptor signaling. TGF-beta1 and IL-1alpha produced by odontogenic tumors/cysts induced osteoclastogenesis directly in the osteoclast precursor cells and indirectly via increased RANKL induction in the stroma. PMID- 27279424 TI - Oxidized Low-Density Lipoprotein Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes by Modulating the TLR4/NF-kappaB Pathway. AB - This study was designed to investigate the apoptosis induced by oxidized low density lipoprotein (ox-LDL) in cultured neonatal rat cardiomyocytes and explore the possible mechanisms. We evaluated whether ox-LDL-induced apoptosis depended in part on the activation of toll-like receptor-4(TLR4)/Nuclear factor kappaB (NF kappaB) signaling pathway. Cells were cultivated with and without ox-LDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess protein or mRNA expressions. Resatorvid (TAK-242), an exogenous synthetic antagonist for TLR4, was used to inhibit TLR4 signal transduction. Dose- and time-dependent apoptotic index of cardiomyocytes occurred after ox-LDL treatment. Incubation of cardiomyocytes with ox-LDL (50 MUg/mL) for 24 hours increased TLR4 and NF-kappaB expressions significantly. Decrease of Bcl 2/Bax protein ratio, activation of caspase-3 and 9 were also detected. Ox-LDL induced cardiomyocyte apoptosis, TLR4 and NF-kappaB expressions were attenuated by pretreatment with TAK-242. In conclusion, our findings indicate that the apoptosis induced by ox-LDL in cultured neonatal rat cardiomyocytes at least in part by modulating the TLR4/NF-kappaB signaling pathway. PMID- 27279425 TI - Fermentation based carbon nanotube multifunctional bionic composites. AB - The exploitation of the processes used by microorganisms to digest nutrients for their growth can be a viable method for the formation of a wide range of so called biogenic materials that have unique properties that are not produced by abiotic processes. Here we produced living hybrid materials by giving to unicellular organisms the nutrient to grow. Based on bread fermentation, a bionic composite made of carbon nanotubes (CNTs) and a single-cell fungi, the Saccharomyces cerevisiae yeast extract, was prepared by fermentation of such microorganisms at room temperature. Scanning electron microscopy analysis suggests that the CNTs were internalized by the cell after fermentation bridging the cells. Tensile tests on dried composite films have been rationalized in terms of a CNT cell bridging mechanism where the strongly enhanced strength of the composite is governed by the adhesion energy between the bridging carbon nanotubes and the matrix. The addition of CNTs also significantly improved the electrical conductivity along with a higher photoconductive activity. The proposed process could lead to the development of more complex and interactive structures programmed to self-assemble into specific patterns, such as those on strain or light sensors that could sense damage or convert light stimulus in an electrical signal. PMID- 27279426 TI - High-responsivity vertical-illumination Si/Ge uni-traveling-carrier photodiodes based on silicon-on-insulator substrate. AB - Si/Ge uni-traveling carrier photodiodes exhibit higher output current when space charge effect is overcome and the thermal effects is suppressed. High current is beneficial for increasing the dynamic range of various microwave photonic systems and simplifying high-bit-rate digital receivers in many applications. From the point of view of packaging, detectors with vertical-illumination configuration can be easily handled by pick-and-place tools and are a popular choice for making photo-receiver modules. However, vertical-illumination Si/Ge uni-traveling carrier (UTC) devices suffer from inter-constraint between high speed and high responsivity. Here, we report a high responsivity vertical-illumination Si/Ge UTC photodiode based on a silicon-on-insulator substrate. When the transmission of the monolayer anti-reflection coating was maximum, the maximum absorption efficiency of the devices was 1.45 times greater than the silicon substrate owing to constructive interference. The Si/Ge UTC photodiode had a dominant responsivity at 1550 nm of 0.18 A/W, a 50% improvement even with a 25% thinner Ge absorption layer. PMID- 27279427 TI - MPQ-cytometry: a magnetism-based method for quantification of nanoparticle-cell interactions. AB - Precise quantification of interactions between nanoparticles and living cells is among the imperative tasks for research in nanobiotechnology, nanotoxicology and biomedicine. To meet the challenge, a rapid method called MPQ-cytometry is developed, which measures the integral non-linear response produced by magnetically labeled nanoparticles in a cell sample with an original magnetic particle quantification (MPQ) technique. MPQ-cytometry provides a sensitivity limit 0.33 ng of nanoparticles and is devoid of a background signal present in many label-based assays. Each measurement takes only a few seconds, and no complicated sample preparation or data processing is required. The capabilities of the method have been demonstrated by quantification of interactions of iron oxide nanoparticles with eukaryotic cells. The total amount of targeted nanoparticles that specifically recognized the HER2/neu oncomarker on the human cancer cell surface was successfully measured, the specificity of interaction permitting the detection of HER2/neu positive cells in a cell mixture. Moreover, it has been shown that MPQ-cytometry analysis of a HER2/neu-specific iron oxide nanoparticle interaction with six cell lines of different tissue origins quantitatively reflects the HER2/neu status of the cells. High correlation of MPQ cytometry data with those obtained by three other commonly used in molecular and cell biology methods supports consideration of this method as a prospective alternative for both quantifying cell-bound nanoparticles and estimating the expression level of cell surface antigens. The proposed method does not require expensive sophisticated equipment or highly skilled personnel and it can be easily applied for rapid diagnostics, especially under field conditions. PMID- 27279428 TI - Genomic expression profiling and bioinformatics analysis on diabetic nephrology with ginsenoside Rg3. AB - Diabetic nephropathy (DN), a common diabetes-related complication, is the leading cause of progressive chronic kidney disease (CKD) and end-stage renal disease. Despite the rapid development in the treatment of DN, currently available therapies used in early DN cannot prevent progressive CKD. The exact pathogenic mechanisms and the molecular events underlying DN development remain unclear. Ginsenoside Rg3 is a herbal medicine with numerous pharmacological effects. To gain a greater understanding of the molecular mechanism and signaling pathway underlying the effect of ginsenoside Rg3 in DN therapy, an RNA sequencing approach was performed to screen differential gene expression in a rat model of DN treated with ginsenoside Rg3. A combined bioinformatics analysis was then conducted to obtain insights into the underlying molecular mechanisms of the disease development, in order to identify potential novel targets for the treatment of DN. Six Sprague-Dawley male rats were randomly divided into 3 groups: Normal control group, DN group and ginsenoside-Rg3 treatment group, with two rats in each group. RNA sequencing was adopted for transcriptome profiling of cells from the renal cortex of DN rat model. Differentially expressed genes were screened out. Cluster analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to analyze the differentially expressed genes. In total, 78 differentially expressed genes in the DN control group were identified when compared with the normal control group, of which 52 genes were upregulated and 26 genes were downregulated. Differential expression of 43 genes was observed in the ginsenoside-Rg3 treatment group when compared with the DN control group, consisting of 10 upregulated genes and 33 downregulated genes. Notably, 21 that were downregulated in the DN control group compared with the control were then shown to be upregulated in the ginsenoside Rg3 treatment group compared with the DN control group. In addition, 7 upregulated genes in the DN control group compared with the control were then shown to be downregulated in the ginsenoside-Rg3 treatment group compared with the DN control group. Cluster analysis based on differentially expressed genes indicated that the transcriptomes are quite different among the samples. Distinct GO terms associated with these groups of genes were shown to be enriched. KEGG pathway analysis demonstrated that differentially expressed genes were predominantly involved in the fatty acid metabolism pathway and peroxisome proliferator-activated receptor (PPAR) signaling pathway. To the best of our knowledge, this study was the first to present whole genome expression profiling in DN with ginsenoside-Rg3 treatment by RNA-Seq. A set of differentially expressed genes and pathways were identified. These data provided an insight into understanding the molecular mechanisms underlying the effect of ginsenoside-Rg3 treatment of DN. PMID- 27279430 TI - Is resistance futile? The role of activated thrombin-activatable fibrinolysis inhibitor resistance in bleeding in factor XI deficiency. PMID- 27279429 TI - Magnetic resonance elastography identifies fibrosis in adults with alpha-1 antitrypsin deficiency liver disease: a prospective study. AB - BACKGROUND: Limited data exist on the clinical presentation and non-invasive detection of liver fibrosis in adults with homozygous Z genotype alpha-1 antitrypsin (AAT) deficiency. AIMS: To compare demographic, biochemical, histological and imaging data of AAT deficient patients to normal-control and biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients, and to assess the diagnostic accuracy of magnetic resonance elastography (MRE) in detecting fibrosis in AAT deficiency. METHODS: Study includes 33 participants, 11 per group, who underwent clinical research evaluation, liver biopsy (AAT and NAFLD groups), and MRE. Histological fibrosis was quantified using a modified Ishak 6 point scale and liver stiffness by MRE. Diagnostic performance of MRE in detecting fibrosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Mean (+/-s.d.) of age and BMI of normal-control, AAT and NAFLD groups was 57 (+/-19), 57 (+/-18), and 57 (+/-13) years, and 22.7 (+/-2.5), 24.8 (+/-4.0) and 31.0 (+/-5.1) kg/m(2) respectively. Serum ALT [mean +/- s.d.] was similar within normal-control [16.4 +/- 4.0] and AAT groups [23.5 +/- 10.8], but was significantly lower in AAT than NAFLD even after adjustment for stage of fibrosis (P < 0.05, P = 0.0172). For fibrosis detection, MRE-estimated stiffness had an area under the ROC curve of 0.90 (P < 0.0001); an MRE threshold of >=3.0 kPa provided 88.9% accuracy, with 80% sensitivity and 100% specificity to detect presence of any fibrosis (stage >=1). CONCLUSIONS: This pilot prospective study suggests magnetic resonance elastography may be accurate for identifying fibrosis in patients with alpha-1 antitrypsin deficiency. Larger validation studies are warranted. PMID- 27279431 TI - A new approach for two-terminal electronic memory devices - Storing information on silicon nanowires. AB - The work described in this paper focuses on the utilisation of silicon nanowires as the information storage element in flash-type memory devices. Silicon nanostructures have attracted attention due to interesting electrical and optical properties, and their potential integration into electronic devices. A detailed investigation of the suitability of silicon nanowires as the charge storage medium in two-terminal non-volatile memory devices are presented in this report. The deposition of the silicon nanostructures was carried out at low temperatures (less than 400 degrees C) using a previously developed a novel method within our research group. Two-terminal non-volatile (2TNV) memory devices and metal insulator-semiconductor (MIS) structures containing the silicon nanowires were fabricated and an in-depth study of their characteristics was carried out using current-voltage and capacitance techniques. PMID- 27279432 TI - Photoisomerization of azobenzenes isolated in cryogenic matrices. AB - 2,2'-Dihydroxyazobenzene (DAB), 2,2'-azotoluene (AT) and azobenzene (AB) were isolated in argon and xenon matrices and their molecular structures and photochemical transformations were characterized by infrared spectroscopy and theoretical calculations. All these compounds can adopt the E and Z isomeric forms around the central CNNC moiety, which can be enriched by several conformational and tautomeric modifications for DAB and AT. A number of DAB and AT isomeric forms were identified for the first time. For DAB, the E azo-enol isomer with two intramolecular six-membered quasi-rings formed via OHN hydrogen bonds was found after deposition. Irradiation with UV light generated a different E azo-enol form with two intramolecular H-bonded five-membered quasi-rings. Phototransformation was shown to be reversible and the forms could be interconverted by irradiation at different wavelengths. The isomerization between these two forms constitutes a direct experimental observation of an E -> E isomerization in azobenzene-type molecules. Further irradiation generated a form(s) bearing both OH and NH groups. For AT, two E isomers with the CH3 groups forming five-membered and five/six-membered quasi-rings with the azo group were observed in the as-deposited matrices. Irradiation of AT with UV light generated a Z form that can be converted back to the E form at different irradiation wavelengths. E-AB was deposited in a xenon matrix and both E -> Z and Z -> E phototransformations were observed (contrary to what was previously reported in an argon matrix where only the Z -> E conversion occurred). AB photoisomerization becomes more pronounced at elevated temperatures, thus indicating that the matrix effects responsible for hindering the AB photoisomerization are essentially due to steric restrictions. The different photoisomerization channels observed for these compounds are discussed in terms of a small-amplitude pedal motion. PMID- 27279433 TI - Multiple-stable anisotropic magnetoresistance memory in antiferromagnetic MnTe. AB - Commercial magnetic memories rely on the bistability of ordered spins in ferromagnetic materials. Recently, experimental bistable memories have been realized using fully compensated antiferromagnetic metals. Here we demonstrate a multiple-stable memory device in epitaxial MnTe, an antiferromagnetic counterpart of common II-VI semiconductors. Favourable micromagnetic characteristics of MnTe allow us to demonstrate a smoothly varying zero-field antiferromagnetic anisotropic magnetoresistance (AMR) with a harmonic angular dependence on the writing magnetic field angle, analogous to ferromagnets. The continuously varying AMR provides means for the electrical read-out of multiple-stable antiferromagnetic memory states, which we set by heat-assisted magneto-recording and by changing the writing field direction. The multiple stability in our memory is ascribed to different distributions of domains with the Neel vector aligned along one of the three magnetic easy axes. The robustness against strong magnetic field perturbations combined with the multiple stability of the magnetic memory states are unique properties of antiferromagnets. PMID- 27279434 TI - Sedimentation stacking diagrams of binary mixtures of thick and thin hard rods. AB - We use Onsager theory and the local density approximation to study sedimentation diffusion equilibrium density profiles of binary mixtures of thick and thin hard rods. We construct stacking diagrams for three diameter ratios, and find that even a simple spindle-shaped phase diagram with only isotropic-nematic demixing can lead to counter-intuitive stacking sequences such as an isotropic phase sandwiched between two nematic phases. For the most complex phase diagram considered here, we find sixteen distinct stacking sequences, including several with five sedimented layers. By adding sedimentation paths to composition pressure and density-density phase diagrams and calculating density and composition profiles, we show that conclusions about bulk phase diagrams of binary mixtures on the basis of sedimentation-diffusion equilibria should be drawn warily. PMID- 27279435 TI - Electromechanical probe and automated indentation maps are sensitive techniques in assessing early degenerated human articular cartilage. AB - Recent advances in the development of new drugs to halt or even reverse the progression of Osteoarthritis at an early-stage requires new tools to detect early degeneration of articular cartilage. We investigated the ability of an electromechanical probe and an automated indentation technique to characterize entire human articular surfaces for rapid non-destructive discrimination between early degenerated and healthy articular cartilage. Human cadaveric asymptomatic articular surfaces (four pairs of distal femurs and four pairs of tibial plateaus) were used. They were assessed ex vivo: macroscopically, electromechanically, (maps of the electromechanical quantitative parameter, QP, reflecting streaming potentials), mechanically (maps of the instantaneous modulus, IM), and through cartilage thickness. Osteochondral cores were also harvested from healthy and degenerated regions for histological assessment, biochemical analyses, and unconfined compression tests. The macroscopic visual assessment delimited three distinct regions on each articular surface: Region I was macroscopically degenerated, region II was macroscopically normal but adjacent to regions I and III was the remaining normal articular surface. Thus, each extracted core was assigned to one of the three regions. A mixed effect model revealed that only the QP (p < 0.0001) and IM (p < 0.0001) were able to statistically discriminate the three regions. Effect size was higher for QP and IM than other assessments, indicating greater sensitivity to distinguish early degeneration of cartilage. When considering the mapping feature of the QP and IM techniques, it also revealed bilateral symmetry in a moderately similar distribution pattern between bilateral joints. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:858-867, 2017. PMID- 27279436 TI - Normative data for phonemic and semantic verbal fluency test in the adult French Quebec population and validation study in Alzheimer's disease and depression. AB - OBJECTIVE: Verbal fluency tasks are principally used to assess lexical access and have shown usefulness for differential diagnosis. The purpose of Study 1 was to provide normative data in the adult French-Quebec population (Canada) for semantic verbal fluency (animals), for two sets of phonemic verbal fluency (TNP and PFL), and for letter P alone (60 seconds per category/letter). The objectives of Study 2 were to establish the diagnostic and predictive validity of the present tasks and normative data in Alzheimer's disease (AD) and major depressive episode (MDE). METHOD: The normative sample consisted of 932 participants aged 19 91 years. Based on multiple linear regressions, equations to calculate Z-scores were provided. To assess validity, performance of 62 healthy participants was compared to 62 participants with AD and 41 with MDE aged over 50. RESULTS: Age and education, but not gender, predicted performance on each verbal fluency task. Healthy adults aged 50 and younger had a better performance on semantic than phonemic verbal fluency. In comparison to MDE, AD participants had lower performance on animals and TNP, but not on letter P. Ninety percent of people with a Z-score <= -1.50 on semantic verbal fluency had AD and the global accuracy was 76.6%. Test-retest reliability over one year was high for both animals (r = .711) and TNP (r = .790) in healthy older participants, but dropped for animals in people with AD (r = .493). CONCLUSIONS: These data will strengthen accurate detection of verbal fluency deficits in French-Quebec adults. PMID- 27279437 TI - Psychophysiological Manifestations Associated With Stress in Students of a Public University in Mexico. AB - PROBLEM: Academic stress is defined as a physiological, emotional, cognitive, and behavioral activation reaction to stimuli. This stress can impact students' ability to cope with the school environment. OBJECTIVE: To identify the psychophysiological manifestations associated with high-level academic stress in public university students in Mexico. METHODS: A representative random sampling of 527 students was evaluated during 2012. The Academic Stress Symptom Inventory and the Rossi classification were used; data were analyzed with a binary logistic regression analysis to estimate association between psychophysiological manifestations and the high level of academic stress in public university students. FINDINGS: Results indicated a meaningful association between high levels of academic stress situations and psychophysiological manifestations such as concentration and memory problems, mental blocks and chronic fatigue, drowsiness, and despair. CONCLUSION: Identifying academic stress situations and students' maladaptive responses may help promote timely attention to psychophysiological manifestations before they exacerbate and become harmful to college students' health. PMID- 27279438 TI - The role of MAPK signaling pathway in the Her-2-positive meningiomas. AB - Meningiomas are common types of adult nerve system tumors. Although most cases are considered benign, due to its high rate of recurrence and easy malignant progression to anaplastic meningioma they present a puzzle for the current treatment. The HER-2 oncogene has important value for meningioma cells development and progression. So far, little is known about the effect on the exact underlying signal pathway and molecular mechanisms of HER-2-positive meningioma cells. The goal of the present study was to determine the effects of HER-2 gene and possible involvement of MAPK signal pathway in human malignant meningioma. We applied q-PCR analysis, immunofluorescence (IF) staining, western blot analysis, animal model, MAPK inhibition, MTT assay and cell invasion analysis for the investigation. The results demonstrated that the downregulation of the expression of HER-2 significantly inhibited cell motility and proliferation of human meningioma cells in vivo. Accordingly, in the HER-2 overexpression meningioma cells with the inhibition of ERK1/2, ERK5, JNK, in the cells with the ERK1/2, ERK5 inhibition, protein expression was markedly suppressed as well as the cell proliferation resistance. No difference was observed in the HER-2-overexpression meningioma cells with the inhibition of JNK. These findings suggest that HER-2 gene can affect the proliferation ability of human meningioma cells in vivo and MAPK signal pathway may contribute to the carcinogenesis and development of human meningiomas combinating with HER-2. PMID- 27279439 TI - Effect of the Medicinal Mushroom, Grifola gargal (Agaricomycetes), on Bone Turnover Markers and Serum Lipids in Middle-Aged and Elderly Japanese Women. AB - A clinical study was performed to examine the effect of the edible mushroom, Grifola gargal, on bone turnover markers and serum lipids in middle-aged and elderly Japanese women. Postmenopausal women aged 51-73 years (mean age, 61 years) received daily oral administration of 5 g G. gargal fruiting bodies (hot air-dried and powdered; G. gargal powder [GGP]). Serum levels of bone alkaline phosphatase (BAP) and lipids and urinary deoxypyridinoline (DPD) levels were measured before and 2 weeks after the start of GGP treatment. As a result, urinary DPD bone resorption marker levels in women treated with GGP decreased significantly. Serum levels of the BAP bone formation marker also tended to increase, but the difference was not significant. By contrast, the atherogenic index decreased and the high-density lipoprotein (HDL) ratio increased significantly. However, there were no statistically significant differences in serum lipids of total cholesterol, HDL cholesterol, and low-density lipoprotein cholesterol. In addition, this study demonstrated for the first time that G. gargal is safe for human consumption. PMID- 27279440 TI - Medicinal Mushrooms in Guatemala. AB - Guatemala, located in Central America, has a long and rich history in the traditional use of edible, medicinal, and hallucinogenic mushrooms. This article describes the use of these mushrooms and presents studies on the scientific validation of native and foreign species. PMID- 27279441 TI - Development and Validation of an LC-MS/MS Method for the Quantification of Agaritine in Mushrooms. AB - Agaritine, an aromatic hydrazine, is found as a secondary metabolite in mushroom species. It is among others suspected to exhibit genotoxic activity. This publication describes the validation of a method for the quantification of agaritine in mushrooms (i.e., extraction and purification by solid phase extraction) and measurement by liquid chromatography with tandem mass spectrometry detection in positive ionization mode. The results show this method to be selective, accurate, and precise. This method could be used for the quality control of pharmaceutical preparations containing mushrooms. PMID- 27279442 TI - Lentinoid and Polyporoid Fungi, Two Generic Conglomerates Containing Important Medicinal Mushrooms in Molecular Perspective. AB - Polyporoid and lentinoid fungi contain the important producers of substances having immunomodulatory, antitumoral, antiviral, and antihyperlipidemic effects. The discovery of several phylogenetic lines within the lentinoid-polyporoid continuum will help with target metabolomic analysis of species still not studied in pharmacological respects. The purpose of the present work was to increase a resolution in the lentinoid-polyporoid phylogenetic zone by means of selection of both the main representatives of Lentinus-related genera and poorly known/intermediate taxa such as Lentinus suavissimus, Neofavolus spp., and the resupinate part of Polyporus (genera Perenniporia and Pachykytospora) in the context of the basic structure of the Polyporales tree. The molecular phylogeny of highlighting all the polyporoid and lentinoid nodes was reconstructed using nLSU ITS rDNA and TEF datasets. The data obtained from ITS, TEF, and LSU coincide in support of core Polyporaceae of 10 clades corresponded to the generic level and 7 of these (Cerioporus, Cladomeris, Favolus, Lentinus, Neofavolus, Picipes, and Polyporus s.str.) contain generic units characterized by polyporoid or lentinoid morphotypes. The other 2 clades containing lentinoid taxa are outside the core Polyporaceae, namely Panus (Meruliaceae, Polyporales) and Neolentinus (Gloeophyllaceae, Gloeophyllales). A new genus, Picipes, is described and 25 new combinations are proposed. PMID- 27279443 TI - Protective Effects of Black Hoof Medicinal Mushroom from Korea, Phellinus linteus (Higher Basidiomycetes), on Osteoporosis In Vitro and In Vivo. AB - The protective effect of Phellinus linteus (ethanol extract) against osteoporosis was investigated using the Saos-2 human osteoblast-like cell line and osteoclasts. A nontoxic concentration of Ph. linteus (10-2 to 10-8 mg mL-1) increased alkaline phosphatase (ALP) (EC 3.1.3.1) activity to a larger extent than soy did. Ph. linteus also attenuated the number and the activity of tartrate resistant acid phosphatase-positive multinucleated osteoclasts. These results indicate that Ph. linteus likely regulated both osteoblasts and osteoclasts, contributing to the protection against osteoporosis. The protective effect of Ph. linteus was examined in ovariectomized (OVX) rats. Histological analysis indicates that Ph. linteus improved trabecular bone mass and reduced osteoclast frequency without affecting lipid droplet accumulation in the femur of OVX rats. A Ph. linteus supplementation for 12 weeks also significantly increased serum ALP activity and reduced urinary deoxypyridinoline level in OVX rats. Ultimately, we found that 12-week Ph. linteus supplementation increased the bone accumulation of minerals, including calcium, magnesium, and phosphorus. Collectively, Ph. linteus protected against osteoporosis by balancing the number of osteoblasts and osteoclasts, which was particularly associated with increased ALP activity in vitro and in vivo and mineral accumulation in bone. PMID- 27279444 TI - Activity of Extracts from Submerged Cultured Mycelium of Winter Mushroom, Flammulina velutipes (Agaricomycetes), on the Immune System In Vitro. AB - Extracts from submerged cultured mycelium of two strains of Flammulina velutipes, a popular culinary mushroom, were obtained by ultrasound and tested in vitro to determine their activity in innate immunity (monocytes/ macrophages). In addition, polyclonal antibodies against the extracts were produced. Both extracts have similar glycoproteins that contain mannose and glucose but have different glycoproteins with galactoseamine units. Two novel immunogenic glycoproteins with molecular weights of 32 and 25 kDa have been revealed. It is thought that these proteins are produced only by submerged cultured mycelium. Both extracts show immune-enhancing activity based on the significant modification of various parameters such as cytokine production, phagocytosis, and reactive oxygen species production. PMID- 27279445 TI - Taxonomic Identity, Geographic Distribution, and Commercial Exploitation of the Culinary-Medicinal Mushroom Pleurotus nebrodensis (Basidiomycetes). AB - An updated overview of the outcome of studies conducted on the culinary-medicinal mushroom Pleurotus nebrodensis is presented by placing emphasis on the clarification of the taxonomic identity of P. nebrodensis and other related taxa possessing entirely white to cream basidiomes, which grow in association with different plants of the family Apiaceae. Cultivation techniques, quality of the product sold and sales price, as well as nutritional and medicinal aspects are discussed. Taking also into consideration the high economic importance of P. nebrodensis, it is essential to proceed with the verification of the commercial strains currently available in the international market under the name of "P. nebrodensis" since it is very probable that many (or most) of them do not represent the real P. nebrodensis. TO confirm this hypothesis, an in silico analysis was conducted on a large of number of ITS1-5.8S-ITS2 rRNA sequences deposited in the National Center for Biotechnology Information database under the name P. nebrodensis. Results demonstrated that all "P nebrodensis" material examined from China (plus several sequences of no reported origin) corresponded to P. eryngii subsp. tuoliensis, with only 2 exceptions, which were grouped within P. eryngii sensu stricto. The real P. nebrodensis biological material from Italy and Greece is certified and is available upon request by the authors at the University of Palermo and the Agricultural University of Athens. PMID- 27279446 TI - A Lectin Purified from Blood Red Bracket Mushroom, Pycnoporus sanguineus (Agaricomycetidae), Mycelium Displayed Affinity Toward Bovine Transferrin. AB - Fungal lectins constitute excellent ligands for development of affinity adsorbents useful in affinity chromatography. In this work, a lectin was purified from Pycnoporus sanguineus (PSL) mycelium using 3 procedures: by affinity chromatography, using magnetic galactosyl-nanoparticles or galactose coupled to Sepharose, and by ionic exchange chromatography (IEC). The highest lectin yield was achieved by IEC (55%); SDS-PAGE of PSL showed 2 bands with molecular mass of 68.7 and 55.2 kDa and IEC displayed 2 bands at pi 5.5 and 5.2. The lectin agglutinates rat erythrocytes, exhibiting broad specificity toward several monosaccharides, including galactose. The agglutination was also inhibited by the glycoproteins fetal calf fetuin, bovine lactoferrin, bovine transferrin, and horseradish peroxidase. The lectin was then used to synthesize an affinity adsorbent (PSL-Sepharose) and the interaction with glycoproteins was evaluated by analyzing their chromatographic behaviors. The strongest interaction with the PSL derivative was observed with transferrin, although lower interactions were also displayed toward fetuin and lactoferrin. These results indicate that the purified PSL constitutes an interesting ligand for the design of affinity adsorbents to be used (i.e., in glycoprotein purification). PMID- 27279447 TI - Cytological Characterization of Anamorphic Fungus Lecanicillium pui and Its Relationship with Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes). AB - Ophiocordyceps sinensis (syn. Cordyceps sinensis), one of the most valuable medicinal mushrooms, has great economic importance on the Tibetan Plateau. We isolated an anamorphic fungus Lecanicillium pui from natural O. sinensis specimens and found that the optimal temperature for its culture on potato dextrose agar media was 25 degrees C. Cell ultrastructure in L. pui hyphae and spores was characterized by transmission electron microscopy, and it was observed that some primary organelles showed the typical fungal features. Five chemical elements were determined in this fungus and niobium was discovered for the first time even with trace amounts. A species-specific method, nested polymerase chain reaction, was established to investigate the colonization of this fungus. Thus, the extensive distribution of L. pui on O. sinensis, in the shape of hyphae or mycelia, suggested that it may have subtle and chronic effects on the growth of the O. sinensis teleomorphic stage. These findings provide a potential reference, in the view of microbial ecology, for the study on the occurrence and mechanism of development of O. sinensis. PMID- 27279448 TI - Wild Edible Mushrooms from Turkey as Possible Anticancer Agents on HepG2 Cells Together with Their Antioxidant and Antimicrobial Properties. AB - This study was designed to reveal cell growth inhibitory potential of six different edible mushrooms: Ramaria flava, Agrocybe molesta, Volvopluteus gloiocephalus, Lactarius deliciosus, Bovista plumbea, and Tricholoma terreum on HepG2 cells together with their antioxidant and antibacterial power. Methanolic extracts of V gloiocephalus and aqueous extracts of R. flava had the most potential cytotoxic effects over HepG2 cells. The best results for 2,2-diphenyl-1 picrylhydrazyl radical scavenging activities were obtained from both aqueous and methanolic extracts of R. flava. Methanolic extracts of T. terreum (IC50 = 1.62 mg/mL) and aqueous extracts of B. plumbea (IC50 = 0.49 mg/mL) showed maximum metal chelating activity. The highest reducing capacities were observed among the methanolic extracts of R. flava (EC50 = 1.65 mg/mL) and aqueous extracts of B. plumbea (EC50 = 1.71 mg/ mL). High-performance liquid chromatography analysis revealed the presence of many phenolic compounds in macrofungi; gallic acid and p coumaric acid were the two main phenolics identified in all extracts. Antibacterial studies indicated that all six tested mushrooms showed antibacterial activity on at least three microorganisms. These results indicate that different extracts of the investigated mushrooms have considerable cytotoxic, antioxidant, and antibacterial properties and may be utilized as a promising source of therapeutics. PMID- 27279449 TI - p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-beta1 expression in rats. AB - Phosphorylated cAMP-responsive element binding protein-1 (p-CREB-1) is an important transcription factor which has been reported to be implicated in fibrogenesis. However, the association between p-CREB-1 and transforming growth factor-beta1 (TGF-beta1)-mediated liver fibrogenesis remains poorly understood. In the present study, exogenous TGF-beta1 recombinant protein was used to activate hepatic stellate cells (HSCs), and we established a rat model of tetrachloromethane (CCl4)-induced liver fibrosis. Loss- and gain-of-function studies were performed to examine the role of p-CREB-1 in liver fibrogenesis, and the detailed mechanism responsible for these effects was further explored using chromatin immunoprecipitation and luciferase reporter gene assays. We found that p-CREB-1 expression was significantly upregulated in a rat model of hepatic fibrosis. We also demonstrated that p-CREB-1 increased TGF-beta1 expression and auto-induction in HSCs, through directly binding to the CRE site within the TGF beta1 promoter in order to enhance its transcriptional activity. Moreover, lentivirus-mediated CREB-1 overexpression promoted hepatic fibrogenesis in rats. These findings suggest that p-CREB-1 may function as a potent profibrogenic factor through the transactivation of TGF-beta1 expression in liver fibrosis. PMID- 27279450 TI - Overcoming the bottlenecks of anaerobic digestion of olive mill solid waste by two-stage fermentation. AB - Two-stage anaerobic digestion (AD) of two-phase olive mill solid waste (OMSW) was applied for reducing the inhibiting factors by optimizing the acidification stage. Single-stage AD and co-fermentation with chicken manure were conducted coinstantaneous for direct comparison. Degradation of the polyphenols up to 61% was observed during the methanogenic stage. Nevertheless the concentration of phenolic substances was still high; the two-stage fermentation remained stable at OLR 1.5 kgVS/m3day. The buffer capacity of the system was twice as high, compared to the one-stage fermentation, without additives. The two-stage AD was a combined process - thermophilic first stage and mesophilic second stage, which pointed out to be the most profitable for AD of OMSW for the reduced hydraulic retention time (HRT) from 230 to 150 days, and three times faster than the single-stage and the co-fermentation start-up of the fermentation. The optimal HRT and incubation temperature for the first stage were determined to four days and 55 degrees C. The performance of the two-stage AD concerning the stability of the process was followed by the co-digestion of OMSW with chicken manure as a nitrogen-rich co substrate, which makes them viable options for waste disposal with concomitant energy recovery. PMID- 27279451 TI - Health-related quality of life in patients with relapsing-remitting multiple sclerosis treated with subcutaneous interferon beta-1a in Iran. AB - PURPOSE: Multiple sclerosis (MS) requires long-term therapy and can affect many aspects of a patient's life, including quality of life. MS patients score lower on health-related quality of life (HRQoL) measures. The efficacy of subcutaneous interferon (IFN) beta-1a has been extensively evaluated by using objective measures but its impact on HRQoL is currently unclear. In this observational study, we evaluated HRQoL of Iranian patients with relapsing-remitting MS (RRMS) treated with IFN beta-1a by using short-form 36 (SF-36) and multiple sclerosis international quality of life (MusiQoL) questionnaires. METHODS: Four hundred recruited RRMS patients were treated with human serum album free IFN beta-1a for 1 year. Patients were required to fill in SF-36 and MusiQoL questionnaires at the first visit and at each follow-up visit. Expanded disability status scale (EDSS) evaluation was performed at baseline and at each visit. Comparisons in HRQoL between visits were calculated using Cohen's d effect size. The relationship between change in EDSS score and the score of each questionnaire was calculated using Pearson correlation coefficients. RESULTS: Three-hundred and eighty three completed the study. Two-hundred and thirty nine were female. Mean (SD) age was 28.75 (+/-5.49). After 1 year, overall MusiQoL Index score effect size was -0.16 and SF-36 physical component and mental component showed overall effect sizes of 0.28 and -0.53, respectively. Mean (range) EDSS change was 1 (1-4). Three-hundred and seventy four were clinically stable with mean (range) EDSS change of 0.1 (-2 0.5). Increase in EDSS was linked to a decrease in both MusiQoL and SF-36. CONCLUSION: We found that, HRQoL did not change significantly over the first year of therapy. Furthermore, decreases in HRQoL were inversely correlated with increases in EDSS score. PMID- 27279452 TI - Mass spectrometry analysis and transcriptome sequencing reveal glowing squid crystal proteins are in the same superfamily as firefly luciferase. AB - The Japanese firefly squid Hotaru-ika (Watasenia scintillans) produces intense blue light from photophores at the tips of two arms. These photophores are densely packed with protein microcrystals that catalyse the bioluminescent reaction using ATP and the substrate coelenterazine disulfate. The squid is the only organism known to produce light using protein crystals. We extracted microcrystals from arm tip photophores and identified the constituent proteins using mass spectrometry and transcriptome libraries prepared from arm tip tissue. The crystals contain three proteins, wsluc1-3, all members of the ANL superfamily of adenylating enzymes. They share 19 to 21% sequence identity with firefly luciferases, which produce light using ATP and the unrelated firefly luciferin substrate. We propose that wsluc1-3 form a complex that crystallises inside the squid photophores, and that in the crystal one or more of the proteins catalyses the production of light using coelenterazine disulfate and ATP. These results suggest that ANL superfamily enzymes have independently evolved in distant species to produce light using unrelated substrates. PMID- 27279455 TI - Social media patient testimonials in implant dentistry: information or misinformation? AB - OBJECTIVES: This study aims to assess the educational value of YouTube patient testimonial videos in implant dentistry and qualitatively analyse the themes mentioned. METHODS: Videos were sampled consecutively on YouTube, using the keywords "dental implant patients' testimonials experience," sorted "by relevance." Patient testimonials on dental implant treatment were examined. Inaudible or non-English videos were excluded. Four calibrated investigators scored the videos for educational content, using a matrix derived from the European Association for Osseointegration information booklet, and demographic details were recorded. Data were analysed qualitatively through inductive thematic analysis. RESULTS: A total of 202 videos were analysed (48 exclusions). Inter-examiner reliability was fair to moderate for informative statements and poor to substantial for misleading statements. A mean of 1.8 informative statements were made per video, compared with misleading, 0.5. Many topics were rarely mentioned, with 19/30 themes appearing fewer than 5% of videos. Patients often informed that implants could improve aesthetics and function, but were misleading on aspects of pain control. Some statements may heighten expectations or imply permanency of treatment. CONCLUSION: Balanced presentation in YouTube testimonials may be limited by bias of clinician-uploaded content. Greater magnitude and breadth of information would improve educational value. Many important parameters of implant therapy were overlooked, whilst information was often potentially misleading. PMID- 27279453 TI - Reductions in all-cause and cause-specific mortality among HIV-infected individuals receiving antiretroviral therapy in British Columbia, Canada: 2001 2012. AB - OBJECTIVES: Since 2006, the British Columbia HIV/AIDS Drug Treatment Program (DTP) has expanded enrolment and dramatically increased its number of participants. We examined the effect this expansion has had on the underlying cause of death in HIV-infected individuals. METHODS: We analysed data from participants aged 18 years and older in the DTP to measure 2-year mortality rates and causes of death from 2001 to 2012. We conducted tests of trend for all-cause and cause-specific mortality, and compared demographics and characteristics of individuals. Cox proportional hazard models were used to determine the risk of death. RESULTS: A total of 8185 participants received antiretroviral therapy (ART) during the study period. Mortality declined from 3.88 per 100 person-years (PY) in 2001-2002 to 2.15 per 100 PY in 2011-2012 (P = 0.02). There were significant decreases in HIV-related deaths (2.34 to 0.56 per 100 PY; P = 0.02) and deaths attributable to chronic liver disease (0.20 to 0.09 per 100 PY; P = 0.01), cardiovascular disease (0.24 to 0.05 per 100 PY; P = 0.03) and suicides (0.47 to 0 per 100 PY; P = 0.003). Multivariate models, adjusted for age, gender, history of injecting drug use, AIDS diagnoses and baseline CD4 cell counts, demonstrated that initiation of ART in all time periods after 2001-2002 was independently associated with reduced mortality (P < 0.001). CONCLUSIONS: We observed declines in HIV-related mortality and certain non-HIV-related causes of death among participants in the BC DTP from 2001 to 2012. These findings suggest that there may be broader benefits to the increasingly liberal HIV treatment guidelines, including reductions in death caused by cardiovascular disease and chronic liver disease. PMID- 27279454 TI - Improved Gate Dielectric Deposition and Enhanced Electrical Stability for Single Layer MoS2 MOSFET with an AlN Interfacial Layer. AB - Transistors based on MoS2 and other TMDs have been widely studied. The dangling bond free surface of MoS2 has made the deposition of high-quality high-k dielectrics on MoS2 a challenge. The resulted transistors often suffer from the threshold voltage instability induced by the high density traps near MoS2/dielectric interface or inside the gate dielectric, which is detrimental for the practical applications of MoS2 metal-oxide-semiconductor field-effect transistor (MOSFET). In this work, by using AlN deposited by plasma enhanced atomic layer deposition (PEALD) as an interfacial layer, top-gate dielectrics as thin as 6 nm for single-layer MoS2 transistors are demonstrated. The AlN interfacial layer not only promotes the conformal deposition of high-quality Al2O3 on the dangling-bond free MoS2, but also greatly enhances the electrical stability of the MoS2 transistors. Very small hysteresis (DeltaVth) is observed even at large gate biases and high temperatures. The transistor also exhibits a low level of flicker noise, which clearly originates from the Hooge mobility fluctuation instead of the carrier number fluctuation. The observed superior electrical stability of MoS2 transistor is attributed to the low border trap density of the AlN interfacial layer, as well as the small gate leakage and high dielectric strength of AlN/Al2O3 dielectric stack. PMID- 27279456 TI - Liquid chromatography with mass spectrometry enantioseparation of pomalidomide on cyclodextrin-bonded chiral stationary phases and the elucidation of the chiral recognition mechanisms by NMR spectroscopy and molecular modeling. AB - A sensitive and validated liquid chromatography with mass spectrometry method was developed for the enantioseparation of the racemic mixture of pomalidomide, a novel, second-generation immunomodulatory drug, using beta-cyclodextrin-bonded stationary phases. Four cyclodextrin columns (beta-, hydroxypropyl-beta-, carboxymethyl-beta-, and sulfobutyl-beta-cyclodextrin) were screened and the effects of eluent composition, flow rate, temperature, and organic modifier on enantioseparation were studied. Optimized parameters, offering baseline separation (resolution = 2.70 +/- 0.02) were the following: beta-cyclodextrin stationary phase, thermostatted at 15 degrees C, and mobile phase consisting of methanol/0.1% acetic acid 10:90 v/v, delivered with 0.8 mL/min flow rate. For the optimized parameter at multiple reaction monitoring mode 274.1-201.0 transition with 20 eV collision energy and 100 V fragmentor voltage the limit of detection and limit of quantitation were 0.75 and 2.00 ng/mL, respectively. Since enantiopure standards were not available, elution order was determined upon comparison of the circular dichroism signals of the separated pomalidomide enantiomers with that of enantiopure thalidomide. The mechanisms underlying the chiral discrimination between the enantiomers were also investigated. Pomalidomide-beta-cyclodextrin inclusion complex was characterized using nuclear magnetic resonance spectroscopy and molecular modeling. The thermodynamic aspects of chiral separation were also studied. PMID- 27279457 TI - Glutamate protects against Ca(2+) paradox-induced injury and inhibits calpain activity in isolated rat hearts. AB - This study determined the effects of glutamate on the Ca(2+) paradoxical heart, which is a model for Ca(2+) overload-induced injury during myocardial ischaemia and reperfusion, and evaluated its effect on a known mediator of injury, calpain. An isolated rat heart was retrogradely perfused in a Langendorff apparatus. Ca(2+) paradox was elicited via perfusion with a Ca(2+) -free Krebs-Henseleit (KH) solution for 3 minutes followed by Ca(2+) -containing normal KH solution for 30 minutes. The Ca(2+) paradoxical heart exhibited almost no viable tissue on triphenyltetrazolium chloride staining and markedly increased LDH release, caspase-3 activity, cytosolic cytochrome c content, and apoptotic index. These hearts also displayed significantly increased LVEDP and a disappearance of LVDP. Glutamate (5 and 20 mmol/L) significantly alleviated Ca(2+) paradox-induced injury. In contrast, 20 mmol/L mannitol had no effect on Ca(2+) paradox. Ca(2+) paradox significantly increased the extent of the translocation of MU-calpain to the sarcolemmal membrane and the proteolysis of alpha-fodrin, which suggests calpain activation. Glutamate also blocked these effects. A non-selective inhibitor of glutamate transporters, dl-TBOA (10 MUmol/L), had no effect on control hearts, but it reversed glutamate-induced cardioprotection and reduction in calpain activity. Glutamate treatment significantly increased intracellular glutamate content in the Ca(2+) paradoxical heart, which was also blocked by dl TBOA. We conclude that glutamate protects the heart against Ca(2+) overload induced injury via glutamate transporters, and the inhibition of calpain activity is involved in this process. PMID- 27279459 TI - Teaching foundational perspective-taking skills to children with autism using the PEAK-T curriculum: single-reversal "I-You" deictic frames. AB - We taught basic perspective-taking tasks to 3 children with autism and evaluated their ability to derive mutually entailed single-reversal deictic relations of those newly established perspective-taking skills. Furthermore, we examined the possibility of transfers of perspective-taking function to novel untrained stimuli. The methods were taken from the PEAK-T training curriculum, and results yielded positive gains for all 3 children to learn basic perspective taking as well as for 2 of the 3 to derive untrained single-reversal I relations following direct training of single-reversal You relations. All participants demonstrated a transfer of stimulus function to untrained stimuli after the single-reversal deictic relations had been mastered. PMID- 27279458 TI - Tanshinone I induces human colorectal cancer cell apoptosis: The potential roles of Aurora A-p53 and survivin-mediated signaling pathways. AB - Colorectal cancer (CRC) is one of the most common malignancies worldwide and a leading cause of cancer death. Despite decades of intensive investigations, effective interventional options are still limited and patient prognosis remains poor. Tanshinone I, an active compound from traditional Chinese herbal medicine Salvia miltiorrhiza Bunge, has been shown to inhibit cell growth of leukemia, lung, and breast cancers. However, whether and how Tanshinone I exerts similar effects on CRC needs to be elucidated. Tanshinone I induced CRC cell apoptosis was characterized and the roles of Aurora A-p53 and survivin-mediated pathways were analyzed in different CRC cell lines. Tanshinone I markedly inhibited CRC cell growth and induced apoptosis in CRC cells with functional p53 protein. Interestingly, Tanshinone I did not exert as much inhibitory effect on normal colon epithelial cells or CRC cells with mutant p53, indicating relative selectivity toward colorectal cancer cells with full presence of p53. In tse cells with wild-type p53, data showed that Tanshinone I mediated Aurora A inhibition results in p53 upregulation, which is required for cell apoptosis. In CRC cells with mutant p53 protein (not able to localize to the nucleus), however, Aurora A knockdown failed to induce CRC cell apoptosis. Instead, data showed that protein level of survivin decreased following Tanshinone I treatment. These observations were further substantiated by the pivotal role of survivin in Tanshinone I mediated apoptosis in CRC cells with p53 mutant. Tanshinone I, a novel natural compound, exerts significant inhibitory effect on CRC cell growth via a mechanism involving either Aurora A-p53 axis or survivin-involving mechanism depending on different intrinsic characteristics of tumor cells. PMID- 27279460 TI - Spontaneous subdural haemorrhage from an arachnoid cyst: a case report and literature review. AB - We discuss a spontaneous subdural haematoma (SDH) arising from an arachnoid cyst in a healthy adult male, presenting with headache and vomiting. Imaging revealed a large SDH communicating with an arachnoid cyst and intracystic haemorrhage. The patient fully recovered with surgical evacuation. We also discuss the causes of spontaneous SDH, and specific risk factors for bleeding in arachnoid cysts, as well as review the literature on spontaneous SDH from arachnoid cysts - a rare but serious complication. PMID- 27279461 TI - The versatility of the serratus anterior free flap in head and neck reconstruction. AB - OBJECTIVES/HYPOTHESIS: Review the literature on the use of the serratus anterior free flap in the head and neck reconstruction and describe new applications of the serratus anterior free flap. STUDY DESIGN: Case series with retrospective chart review and literature review. METHODS: A PubMed literature review was performed using the search terms "serratus free flap," "serratus skull base," "serratus scalp," and "serratus free tissue transfer." One hundred and seventy six articles were identified, 22 of which included at least one head and neck reconstructive case utilizing the serratus free flap. Twenty-two articles were identified since 1982 that discussed the use of the serratus anterior free flap for reconstruction in the head and neck. However, most of these were harvested in conjunction with latissimus muscle. RESULTS: We present a case series of 15 patients in whom the serratus anterior muscle free flap was used alone for head and neck reconstruction. In seven of these patients, we used the serratus for coverage of the newly created pharynx after total laryngectomy, which has not previously been reported. CONCLUSION: The serratus anterior free muscle flap has great versatility in reconstruction of the head and neck. Because of its low donor site morbidity, thinness, and pliability, as well as its ease of harvest, it is ideal for reconstruction of the skull base and scalp. We have also found that it is ideal for muscle coverage of the newly reconstructed pharynx after total laryngectomy. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:568-573, 2017. PMID- 27279462 TI - Evaluating the Performance Improvement Preferences of Disability Service Managers: An Exploratory Study Using Gilbert's Behavior Engineering Model. AB - BACKGROUND: Front-line managers play an important role in managing the performance of staff working in services for people with intellectual disability, but little is known about the practices they prefer to use to improve staff performance and whether these align with what research has shown to be effective. METHOD: This study comprised two phases. First, the present authors tested the validity and reliability of a short questionnaire designed to evaluate managers' preferences for performance improvement practices. Then, the present authors collected and analysed responses from 175 managers working in disability services in Queensland, Australia. RESULTS: The questionnaire demonstrated good content validity, concurrent validity and test-retest reliability. The participants believed strategies related to changing employee individual characteristics to be more effective than strategies aimed at improving environmental factors. CONCLUSIONS: This study provides important considerations regarding the professional development needs of front-line managers working in organizations that provide services to people with intellectual disability. PMID- 27279463 TI - Analysis of antenatal-onset cerebral palsy secondary to transient ischemia in utero using a national database in Japan. AB - AIM: We conducted a retrospective analysis of summary medical reports of children diagnosed with cerebral palsy (CP) to identify clinical features of antenatal onset of CP secondary to transient ischemia in utero. METHODS: The 658 brief summary reports available in the Japan Obstetric Compensation System for Cerebral Palsy were screened, and we identified cases of singleton pregnancy, delivered at gestational age >= 33 weeks and those with cord blood gas pH >= 7.20. Of the 137 cases identified, 84 were excluded for the following reasons: no evidence of ischemic brain lesion, clear post-natal causative factor of CP, presence of a congenital condition, and sentinel hypoxic event, such as uterine rupture. The demographic profiles of the 53 cases included in our analysis were compared to identify those with and without an abnormal variability in fetal heart rate. RESULTS: Between-group comparison identified an association between abnormal heart rate variability and a lower Apgar score at 1 min (2 vs 6; P < 0.001) and 5 min (5.5 vs 8; P = 0.002), and more frequent episodes of fetal movement loss (41% vs 10%; P = 0.027). An hypoxic event <= 1 week before delivery was more likely to be associated with abnormal heart rate variability (89%) and low Apgar score (82%), while events at > 1 week were associated with development of polyhydramnios (44%). CONCLUSION: In utero transient ischemic events can contribute to term or near-term CP. Careful follow-up is recommended for fetuses with a history of fetal movement loss, abnormal variability in heart rate, and polyhydramnios of unknown causes. PMID- 27279464 TI - Analyzing the 22-item Sino-Nasal Outcome Test using item response theory. AB - BACKGROUND: The 22-item Sino-Nasal Outcome Test (SNOT-22) is a widely applied patient-reported outcome instrument used to assess the severity of symptoms associated with chronic rhinosinusitis. The purpose of this study was to evaluate the measurement performance of the SNOT-22 instrument on an item-level basis, in a sample of patients awaiting elective surgery for chronic rhinosinusitis. METHODS: This study involved secondary analysis of SNOT-22 data that was prospectively collected from patients diagnosed with chronic rhinosinusitis and awaiting endoscopic sinus surgery in Vancouver, Canada. This study used classic test theory and a 2-parameter graded-response model to evaluate the SNOT-22 items' abilities to measure the severity of chronic rhinosinusitis in terms of patients' self-reported symptoms. This approach models each item's discriminability and difficulty, which provides insight into how well they respectively measure symptoms related to chronic rhinosinusitis. RESULTS: Factor analyses indicated that there are 5 domains of measurement in the SNOT-22. The majority of items demonstrated strong discriminability between symptom severities. Likewise, most of the items demonstrated strong difficulty measuring the symptoms across their range of levels. The exception was those items related to psychological symptoms. Differential item functioning demonstrated that very few of the SNOT-22 items were answered significantly differently by gender or age subgroups. CONCLUSION: This item-level analysis demonstrates that, in general, the SNOT-22 is a strong instrument. Items related to psychological symptoms require further investigation and warrant a supplemental patient-reported outcome instrument. PMID- 27279466 TI - Comparison of cytologic preparation methods in endoscopic ultrasound-guided fine needle aspiration for diagnosis of pancreatic adenocarcinoma. AB - BACKGROUND: There are few studies about the diagnostic yield of cytologic preparation method of pancreatic samples obtained by Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to compare the accuracy of ThinPrep((r)) and smear method in diagnosis of pancreatic cancer. METHODS: A total of 125 EUS-FNA procedures were performed between July 2010 and June 2015. Patients in group I (n = 36; July 2010 to June 2014) had cytology slides prepared by consecutive allocation of samples. Patients in group II (n = 12; July 2014 to June 2015) had cytology slides prepared by alternately allocation of samples. RESULTS: There were 24 men and 24 women (median age: 67 years; range 39-84). The median size of lesions was 3.9 cm (range; 1.4-7.2 cm). The locations of the pancreatic cancer were 10 in head (20.8%), 21 in body (43.8%), and 17 in tail (35.4%). The ThinPrep((r)) method confirmed malignancy in 35 of 48 cases (72.9%). On the other hand, the smear method confirmed malignancy in 44 of 48 cases (91.7%). The diagnostic yield of smear method was statistically higher than liquid method (P = 0.012). Also, smear method is superior to liquid method in both consecutive and alternative allocation method. ThinPrep((r)) provided a correct diagnosis in one case where the smear method was incorrect. CONCLUSIONS: Smear method was a superior preparation method to liquid method in diagnosis of pancreatic cancer, even if splitting method was not used and variable allocation method was used. PMID- 27279467 TI - Feasibility and effect of in-home physical exercise training delivered via telehealth before bariatric surgery. AB - Optimal physical activity (PA) interventions are needed to increase PA in individuals with severe obesity, and optimize the results of bariatric surgery (BS). The aim of this study was to assess the feasibility and effect of Pre Surgical Exercise Training (PreSET) delivered in-home via telehealth (TelePreSET) in subjects awaiting BS. Six women following the TelePreSET were compared to the women from a previous study (12 performing the PreSET in a gymnasium and 11 receiving usual care). In-home TelePreSET (12-weeks of endurance and strength training) was supervised twice weekly using videoconferencing. Physical fitness, quality of life, exercise beliefs, anthropometric measures and telehealth perception were assessed before and after 12-weeks. Satisfaction was evaluated with questionnaires at the end of the intervention. The TelePreSET participants attended 96% of the exercise sessions, and were very satisfied by the TelePreSET. The baseline telehealth perception score was high, and increased significantly after the intervention. The TelePreSET group significantly increased their physical fitness compared to the usual care group. No significant change was noted in other outcomes. The TelePreSET is feasible and seems effective to improve the physical fitness of women awaiting BS. Further studies are needed to confirm beneficial effects of this innovative mode of delivery. PMID- 27279465 TI - Higher Plasma S100B Concentrations in Schizophrenia Patients, and Dependently Associated with Inflammatory Markers. AB - Glial damage and immune dysfunction are involved in pathogenesis of schizophrenia. However, interaction between glial damage and immune dysfunction in schizophrenia is undefined. This study aims to compare plasma S100 calcium binding protein (S100B) levels between schizophrenia patients and healthy participants, and to determine if immune markers are independently related with concentration of S100B in schizophrenia patients. Forty-one schizophrenia patients and thirty-three healthy volunteers were enrolled. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of plasma S100B and inflammatory markers. We found that concentrations of S100B were elevated in schizophrenia patients than healthy participants (p < 0.05), and were negatively related with the severity of symptoms (p = 0.046). Receiver operating characteristic (ROC) curve analysis showed that different S100B levels between schizophrenia and healthy participants can be used as a clinical diagnostic factor (predictive value: 0.666, p = 0.015). Multiple linear regression analysis found that length of illness (Beta = -0.161), plasma levels of inflammatory regulation factors (including TGF-beta1, logIL-23 and logIL-10) (Beta = 0.119, 0.475, 0.514) were independently associated with concentrations of S100B (Adjusted R(2) = 0.897, p < 0.001). Therefore, our results suggest the possible function of S100B in pathogenesis of schizophrenia, and implicate the important role of autoimmune response and balance to glial dysfunction in patients with schizophrenia. PMID- 27279468 TI - DTC teledermatology: Access to the specialists' specialist - meeting an unmet need. PMID- 27279469 TI - EDTITRATE (Emergency Department Telemedicine Initiative to Rapidly Accommodate in Times of Emergency). AB - Objective Emergency Department (ED) patient volumes are unpredictable, which can result in service delays and patients leaving without care. We initiated a programme of emergency physician (EP) telepresence in the ED with the objectives of assessing feasibility, safety, patient and provider acceptance, and throughput time. Methods This was a prospective convenience study. Patients presenting to the ED during operation of the study who were planned for placement in the waiting room were considered for enrolment. A faculty EP conducted patient evaluations via telepresence with confirmatory evaluation by the onsite faculty EP prior to disposition. Patient care was either taken to completion by the telemedicine EP or initiated and handed off to the onsite team. Measures included patient demographics, triage class (ESI 1-5), throughput time and a single question satisfaction survey (rating 1-5, 5 most favourable) completed by patients, registered nurses and EPs. Patients were called within 3 days and the electronic health record reviewed at 7 days looking for unscheduled visits and adverse events. Results In total, 130 patients were enrolled. Mean triage class was 3.9 with a median throughput of 150 minutes (IQR = 116.5, 206). Non telemedicine patients during the same time period with similar triage classes had a median throughput of 287 minutes (IQR = 199, 408). Mean satisfaction scores were: patient 4.91, nurse 4.75, onsite EP 4.47 and telemedicine EP 4.79. There was one potential misdiagnosis and no adverse events. Conclusion Patient evaluation by EP via telepresence is feasible, safe, readily accepted by patients and providers and associated with reduced throughput time. PMID- 27279470 TI - Latent cytomegalovirus infection exacerbates experimental pulmonary fibrosis by activating TGF-beta1. AB - The aim of the present study was to investigate the hypotheses that cytomegalovirus (CMV) may trigger idiopathic pulmonary fibrosis (IPF) in a susceptible host and/or that the presence of CMV may alter IPF in response to a well-defined trigger of pulmonary fibrosis. A mouse model of murine CMV (MCMV) infection was established, and the mice were divided into a control group, bleomycin group and an MCMV+bleomycin group. Changes in the weights of the mice were determined in the three groups. Pulmonary fibrosis was detected using a histopathological method. The activity of transforming growth factor (TGF)-beta1 was measured, and the levels of E-cadherin, Vimentin and phosphorylated (phospho) small mothers against decapentaplegic (SMAD)2 were determined using western blot analysis. MCMV was found to invade the lungs, however, it did not cause pulmonary fibrosis. The progression of fibrosis in the mice treated with MCMV+bleomycin was more rapid, compared with that in the control mice. The protein levels of Vimentin and phospho-SMAD2 were upregulated, whereas the level of E-cadherin was downregulated in the MCMV+bleomycin group,. The results suggested that latent MCMV infection aggravated pulmonary fibrosis in the mouse model, possibly through the activation of TGF-beta1. PMID- 27279471 TI - Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof-of-concept, Randomized, Double-blind, Placebo-controlled Clinical Trial. AB - Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 +/- 8.2 years, 70.5% females, HbA1c 5.8 +/- 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 +/- 42.4 vs. +13.4 +/- 52.6 mg/dL, p < 0.05). Homoeostasis model assessment-B was increased (+17.11 +/- 10.69, +5.24 +/- 4.10, and +0.86 +/- 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 +/- 21.2, +8.4 +/- 18.1, and +24.2 +/- 14.5; oxidized low-density lipoprotein: 19.7 +/- 8.5, -13.1 +/- 7.2, and -2.2 +/- 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27279472 TI - Stem cell factor promotes in vitro ovarian follicle development in the domestic cat by upregulating c-kit mRNA expression and stimulating the phosphatidylinositol 3-kinase/AKT pathway. AB - In the present study we examined the effects of stem cell factor (SCF; 50 vs 100ngmL-1) alone or in combination with epidermal growth factor (EGF; 100ngmL-1) on: (1) the in vitro viability and growth of cat follicles within ovarian cortices; (2) phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) phosphorylation; and (3) c-kit and FSH receptor (FSHr) mRNA expression. At 100ngmL-1, SCF increased (P<=0.05) the percentage and size of secondary follicles after 14 days of in vitro culture and sustained AKT phosphorylation after 3 days incubation. EGF suppressed this beneficial effect and reduced (P<=0.05) the percentage of structurally normal follicles and FSHr expression when combined with 100ngmL-1 SCF. Expression of c-kit mRNA was higher (P<=0.05) in the presence of 100ngmL-1 SCF compared with fresh follicles and cohorts cultured under other conditions. A c-kit inhibitor suppressed follicle growth and reduced AKT phosphorylation. Collectively, the results demonstrate that SCF promotes cat follicle development by upregulating c-kit mRNA expression and AKT phosphorylation. EGF suppresses the stimulating effect of SCF, leading to downregulation of FSHr expression. PMID- 27279473 TI - Dietary flavonoid intake and the risk of stroke: a dose-response meta-analysis of prospective cohort studies. AB - OBJECTIVE: To clarify and quantify the potential association between intake of flavonoids and risk of stroke. DESIGN: Meta-analysis of prospective cohort studies. DATA SOURCE: Studies published before January 2016 identified through electronic searches using PubMed, Embase and the Cochrane Library. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective cohort studies with relative risks and 95% CIs for stroke according to intake of flavonoids (assessed as dietary intake). RESULTS: The meta-analysis yielded 11 prospective cohort studies involving 356 627 participants and more than 5154 stroke cases. The pooled estimate of the multivariate relative risk of stroke for the highest compared with the lowest dietary flavonoid intake was 0.89 (95% CI 0.82 to 0.97; p=0.006). Dose-response analysis indicated that the summary relative risk of stroke for an increase of 100 mg flavonoids consumed per day was 0.91 (95% CI 0.77 to 1.08) without heterogeneity among studies (I(2)=0%). Stratifying by follow-up duration, the relative risk of stroke for flavonoid intake was 0.89 (95% CI 0.81 to 0.99) in studies with more than 10 years of follow-up. CONCLUSIONS: Results from this meta-analysis suggest that higher dietary flavonoid intake may moderately lower the risk of stroke. PMID- 27279474 TI - Does employee participation in workplace health promotion depend on the working environment? A cross-sectional study of Danish workers. AB - OBJECTIVES: To investigate if participation in workplace health promotion (WHP) depends on the work environment. METHODS: Questionnaire data on participation in WHP activities (smoking cessation, healthy diet, exercise facilities, weekly exercise classes, contact with health professionals, health screenings) and the work environment (social support, fatiguing work, physical, quantitative and emotional demands, job control and WHP availability setting) were collected cross sectionally in 2010 in a representative sample (n=10 605) of Danish workers. Binary regression analyses of the association between work environment characteristics and participation in WHP were conducted and adjusted for age, gender and industry. RESULTS: WHP offered during leisure time was associated with lower participation in all measured activities compared with when offered during working hours. Low social support and fatiguing work were associated with low participation in WHP. No associations with participation in WHPs were observed for physical work or quantitative demands, work pace or job strain. However, high physical demands/low job control and high emotional demands/low job control were associated with low participation. CONCLUSIONS: Lower participation in WHP was associated with programmes during leisure, low social support, very fatiguing work and high physical or emotional demands with low job control. This suggests that to obtain proper effect of health promotion in a workplace setting, a good work environment is essential. PMID- 27279475 TI - Factors associated with prolonged length of stay following cardiac surgery in a major referral hospital in Oman: a retrospective observational study. AB - OBJECTIVES: Two objectives were set for this study. The first was to identify factors influencing prolonged postoperative length of stay (LOS) following cardiac surgery. The second was to devise a predictive model for prolonged LOS in the cardiac intensive care unit (CICU) based on preoperative factors available at admission and to compare it against two existing cardiac stratification systems. DESIGN: Observational retrospective study. SETTINGS: A tertiary hospital in Oman. PARTICIPANTS: All adult patients who underwent cardiac surgery at a major referral hospital in Oman between 2009 and 2013. RESULTS: 30.5% of the patients had prolonged LOS (>=11 days) after surgery, while 17% experienced prolonged ICU LOS (>=5 days). Factors that were identified to prolong CICU LOS were non elective surgery, current congestive heart failure (CHF), renal failure, combined coronary artery bypass graft (CABG) and valve surgery, and other non-isolated valve or CABG surgery. Patients were divided into three groups based on their scores. The probabilities of prolonged CICU LOS were 11%, 26% and 28% for group 1, 2 and 3, respectively. The predictive model had an area under the curve of 0.75. Factors associated with prolonged overall postoperative LOS included the body mass index, the type of surgery, cardiopulmonary bypass machine use, packed red blood cells use, non-elective surgery and number of complications. The latter was the most important determinant of postoperative LOS. CONCLUSIONS: Patient management can be tailored for individual patient based on their treatments and personal attributes to optimise resource allocation. Moreover, a simple predictive score system to enable identification of patients at risk of prolonged CICU stay can be developed using data that are routinely collected by most hospitals. PMID- 27279476 TI - Consumer concerns about paracetamol: a retrospective analysis of a medicines call centre. AB - OBJECTIVES: To identify consumer information needs about paracetamol, the most commonly used analgesic and antipyretic worldwide. DESIGN: Retrospective analysis of medicines questions from the public. SETTING: Australian consumer medicines call centre. PARTICIPANTS: Callers to National Prescribing Service Medicines Line between September 2002 and June 2010 (n=123 217). MAIN OUTCOME MEASURES: Enquiry profile: demographics, enquiry type and concurrent medicines included in paracetamol calls; question themes derived from subset of call narratives. RESULTS: Paracetamol comprised part of the enquiry in 5.2% of calls (n=6367). The caller age distribution for paracetamol calls was skewed towards a younger cohort, with 45.2% made by those aged 25-44 vs 37.5% in 'rest of calls'. Significantly more paracetamol-related calls were made for a child (23.7%) compared with 'rest of calls' (12.7%, p<0.001). The most frequent concurrently asked about medicines were codeine (11%, n=1521) and ibuprofen (6.4%, n=884). Questions underpinned by paracetamol risk (interaction, use in pregnancy/lactation or other safety concerns) predominated (55.8%). When individual paracetamol enquiry types were compared with 'rest of calls', efficacy was most frequent (24.9% vs 22.8%); however, interaction (21.5% vs 14.8%), administration (15.5% vs 11%) and pregnancy/lactation (13.8% vs 8.3%) categories were more prevalent for paracetamol calls (all p<0.001). Enquiry type frequency also varied by patient age group, with questions about administration more common in younger groups and efficacy dominating in those over 45. Narrative analysis of over-represented paracetamol enquiry types showed specific concerns relevant to life stages: young children, those of reproductive age and the elderly. CONCLUSIONS: Consumers have many concerns about the use of paracetamol that may be under-recognised by healthcare providers, with the nature of enquiries differing across life stages. These concerns are not adequately addressed by available consumer information. Improving access to targeted information about paracetamol would promote the safe and effective use of this common medicine. PMID- 27279477 TI - Trends of CT utilisation in an emergency department in Taiwan: a 5-year retrospective study. AB - OBJECTIVES: To investigate the association between the trends of CT utilisation in an emergency department (ED) and changes in clinical imaging practice and patients' disposition. SETTING: A hospital-based retrospective observational study of a public 1520-bed referral medical centre in Taiwan. PARTICIPANTS: Adult ED visits (aged >=18 years) during 2009-2013, with or without receiving CT, were enrolled as the study participants. MAIN OUTCOME MEASURES: For all enrolled ED visits, we retrospectively analysed: (1) demographic characteristics, (2) triage categories, (3) whether CT was performed and the type of CT scan, (4) further ED disposition, (5) ED cost and (6) ED length of stay. RESULTS: In all, 269 239 adult ED visits (148 613 male patients and 120 626 female patients) were collected during the 5-year study period, comprising 38 609 CT scans. CT utilisation increased from 11.10% in 2009 to 17.70% in 2013 (trend test, p<0.001). Four in 5 types of CT scan (head, chest, abdomen and miscellaneous) were increasingly utilised during the study period. Also, CT was increasingly ordered annually in all age groups. Although ED CT utilisation rates increased markedly, the annual ED visits did not actually increase. Moreover, the subsequent admission rate, after receiving ED CT, declined (59.9% in 2009 to 48.2% in 2013). CONCLUSIONS: ED CT utilisation rates increased significantly during 2009-2013. Emergency physicians may be using CT for non-emergent studies in the ED. Further investigation is needed to determine whether increasing CT utilisation is efficient and cost-effective. PMID- 27279479 TI - Anxiolytic and neuroprotective effects of the Traditional Chinese Medicinal formulation Dan-zhi-xiao-yao-san in a rat model of chronic stress. AB - Dan-zhi-xiao-yao-san is a Traditional Chinese Medicinal formulation widely used for the treatment of neuropsychological disorders. The present study examined the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san in a rat model of chronic stress. The results of an elevated plus maze test showed that Dan-zhi xiao-yao-san significantly attenuated the levels of anxiety-induced stress as evidenced by increases in the time spent in the open arm region, as well as the percentage of entries into this area. In addition, Dan-zhi-xiao-yao-san alleviated stress-induced neuronal death, as indicated by histological examination. Furthermore, mechanistic studies suggested that the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san may be mediated via attenuation of chronic stress-induced upregulation of alpha-synuclein and corticosterone, and downregulation of protein phosphatase 2A (PP2A) in the hippocampal region of the brain at the mRNA and protein level. In addition, Dan-zhi-xiao-yao-san decreased the serum levels of stress-induced corticosterone in the model animals. In conclusion, the present study demonstrated that Dan-zhi-xiao-yao-san exerted anxiolytic and neuroprotective effects in a rat model of chronic stress via attenuation of stress-induced upregulation of alpha-synuclein and corticosterone, and downregulation of PP2A in the hippocampus. PMID- 27279478 TI - Older, vulnerable patient view: a pilot and feasibility study of the patient measure of safety (PMOS) with patients in Australia. AB - OBJECTIVES: The UK-developed patient measure of safety (PMOS) is a validated tool which captures patient perceptions of safety in hospitals. We aimed (1) to investigate the extent to which the PMOS is appropriate for use with stroke, acute myocardial infarction (AMI) and hip fracture patients in Australian hospitals and (2) to pilot the PMOS for use in a large-scale, national study 'Deepening our Understanding of Quality in Australia' (DUQuA). PARTICIPANTS: Stroke, AMI and hip fracture patients (n=34) receiving care in 3 wards in 1 large hospital. METHODS: 2 phases were conducted. First, a 'think aloud' study was used to determine the validity of PMOS with this population in an international setting, and to make amendments based on patient feedback. The second phase tested the revised measure to establish the internal consistency reliability of the revised subscales, and piloted the recruitment and administration processes to ensure feasibility of the PMOS for use in DUQuA. RESULTS: Of the 43 questions in the PMOS, 13 (30%) were amended based on issues patients highlighted for improvement in phase 1. In phase 2, a total of 34 patients were approached and 29 included, with a mean age of 71.3 years (SD=16.39). Internal consistency reliability was established using interitem correlation and Cronbach's alpha for all but 1 subscale. The most and least favourably rated aspects of safety differed between the 3 wards. A study log was categorised into 10 key feasibility factors, including liaising with wards to understand operational procedures and identify patterns of patient discharge. CONCLUSIONS: Capturing patient perceptions of care is crucial in improving patient safety. The revised PMOS is appropriate for use with vulnerable older adult groups. The findings from this study have informed key decisions made for the deployment of this measure as part of the DUQuA study. PMID- 27279480 TI - Silencing FAT10 inhibits metastasis of osteosarcoma. AB - Metastasis is the main challenge of osteosarcoma treatment. Herein, we first reveal the oncogenic role of FAT10 in metastasis of osteosarcoma. FAT10 was upregulated in osteosarcoma, especially in metastatic osteosarcoma. High level of FAT10 was associated with poorer prognosis of osteosarcoma patients. Moreover, Transwell and Matrigel assays revealed that silencing FAT10 significantly inhibited the invasive and migratory abilities of osteosarcoma cells. Metastasis assay in vivo showed that silencing FAT10 decreased the number of mice with distant metastasis. We also found that FAT10 may act its oncogenic functions through regulating HOXB9. Collectively, the results suggested that FAT10 may be a novel therapeutic target for osteosarcoma patients. PMID- 27279481 TI - Integrating landfill bioreactors, partial nitritation and anammox process for methane recovery and nitrogen removal from leachate. AB - A new process consisting of a landfill bioreactor, partial-nitritation (PN) and the anammox process has been developed for landfill leachate treatment. In this study, the landfill bioreactor exhibited excellent performance in methane-rich biogas recovery, with a specific biogas yield of 0.47 L gas g(-1) COD and methane percentages of 53-76%. PN was achieved in the aerobic reactor by high free ammonia (101 +/- 83 mg NH3 L(-1)) inhibition for nitrite-oxidizing bacteria, and the desired PN effluent composition (effluent nitrite: ammonium ratio of 1.1 +/- 0.3) was controlled by adjusting the alkalinity concentration per unit of ammonium oxidized to approximately 14.3 mg CaCO3 mg(-1) N in the influent. The startup of anammox process was successfully achieved with a membrane bioreactor in 160 d, and a maximum nitrogen removal rate of 216 mg N L(-1) d(-1) was attained for real landfill leachate treatment. The quantitative polymerase chain reaction results confirmed that the cell-specific anammox activity was approximately 68-95 fmol N cell(-1) d(-1), which finally led to the stable operation of the system. PMID- 27279482 TI - Inhibition of herpes simplex virus 1 gene expression and replication by RNase P associated external guide sequences. AB - An external guide sequence (EGS) is a RNA sequence which can interact with a target mRNA to form a tertiary structure like a pre-tRNA and recruit intracellular ribonuclease P (RNase P), a tRNA processing enzyme, to degrade target mRNA. Previously, an in vitro selection procedure has been used by us to engineer new EGSs that are more robust in inducing human RNase P to cleave their targeted mRNAs. In this study, we constructed EGSs from a variant to target the mRNA encoding herpes simplex virus 1 (HSV-1) major transcription regulator ICP4, which is essential for the expression of viral early and late genes and viral growth. The EGS variant induced human RNase P cleavage of ICP4 mRNA sequence 60 times better than the EGS generated from a natural pre-tRNA. A decrease of about 97% and 75% in the level of ICP4 gene expression and an inhibition of about 7,000 and 500-fold in viral growth were observed in HSV infected cells expressing the variant and the pre-tRNA-derived EGS, respectively. This study shows that engineered EGSs can inhibit HSV-1 gene expression and viral growth. Furthermore, these results demonstrate the potential for engineered EGS RNAs to be developed and used as anti-HSV therapeutics. PMID- 27279483 TI - Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line. AB - In recent years, genome-wide RNA expression analysis has become a routine tool that offers a great opportunity to study and understand the key role of genes that contribute to carcinogenesis. Various microarray platforms and statistical approaches can be used to identify genes that might serve as prognostic biomarkers and be developed as antitumor therapies in the future. Metastatic renal cell carcinoma (mRCC) is a serious, life-threatening disease, and there are few treatment options for patients. In this study, we performed one-color microarray gene expression (4*44K) analysis of the mRCC cell line Caki-1 and the healthy kidney cell line ASE-5063. A total of 1,921 genes were differentially expressed in the Caki-1 cell line (1,023 upregulated and 898 downregulated). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) approaches were used to analyze the differential-expression data. The objective of this research was to identify complex biological changes that occur during metastatic development using Caki-1 as a model mRCC cell line. Our data suggest that there are multiple deregulated pathways associated with metastatic clear cell renal cell carcinoma (mccRCC), including integrin-linked kinase (ILK) signaling, leukocyte extravasation signaling, IGF-I signaling, CXCR4 signaling, and phosphoinositol 3-kinase/AKT/mammalian target of rapamycin signaling. The IPA upstream analysis predicted top transcriptional regulators that are either activated or inhibited, such as estrogen receptors, TP53, KDM5B, SPDEF, and CDKN1A. The GSEA approach was used to further confirm enriched pathway data following IPA. PMID- 27279484 TI - Role of Nox4 and p67phox subunit of Nox2 in ROS production in response to increased tubular flow in the mTAL of Dahl salt-sensitive rats. AB - Nox4 and Nox2 are the most abundant NADPH oxidases (Nox) in the kidney and have been shown to contribute to hypertension, renal oxidative stress, and injury in Dahl salt-sensitive (SS) hypertensive rats. The present study focused on the role of Nox4 and p67phox/Nox2 in the generation of H2O2 and O2 (.-) in the renal medullary thick ascending limb of Henle (mTAL) of SS rats in response to increasing luminal flow (from 5 to 20 nl/min). Nox4 and p67phox/Nox2 genes were found to be expressed in the mTAL of SS rats. Responses of SS rats were compared with those of SS rats with knockout of Nox4 (SS(Nox4-/-)) or functional mutation of p67phox (SS(p67phox-/-)). Nox4 was the dominant source of increased intracellular H2O2 production in response to increased luminal flow as determined using the fluorescent dye peroxyfluor 6-AM (PF6-AM). The rate of mitochondrial H2O2 production [as determined by mitochondria peroxy yellow 1 (mitoPY1)] was also significantly reduced in SS(Nox4-/-) compared with SS rats, but not in SS(p67phox-/-) rats. In contrast, intracellular superoxide (O2 (.-)) production (the ratio of ethidium to dihydroethidium) in the mTAL of SS(Nox4-/-) rats was nearly identical to that of SS rats in response to luminal flow, indicating that Nox4 made no measurable contribution. mTAL O2 (.-) production was reduced in SS(p67phox-/-) compared with SS rats at the lower luminal flow of 5 nl/min and progressively increased when perfusion was changed to 20 nl/min. We conclude that increased mTAL luminal flow results in increases in intracellular and mitochondrial H2O2, which are dependent on the presence of Nox4, and that p67phox/Nox2 accounts solely for increases in O2 (.-) production. PMID- 27279485 TI - Secretin, at the hub of water-salt homeostasis. AB - Water and salt metabolism are tightly regulated processes. Maintaining this milieu interieur within narrow limits is critical for normal physiological processes to take place. Disturbances to this balance can result in disease and even death. Some of the better-characterized regulators of water and salt homeostasis include angiotensin II, aldosterone, arginine vasopressin, and oxytocin. Although secretin (SCT) was first described >100 years ago, little is known about the role of this classic gastrointestinal hormone in the maintenance of water-salt homeostasis. In recent years, increasing body of evidence suggested that SCT and its receptor play important roles in the central nervous system and kidney to ensure that the mammalian extracellular fluid osmolarity is kept within a healthy range. In this review, we focus on recent advances in our understanding of the molecular, cellular, and network mechanisms by which SCT and its receptor mediate the control of osmotic homeostasis. Implications of hormonal cross talk and receptor-receptor interaction are highlighted. PMID- 27279486 TI - Osmotically inactive sodium and potassium storage: lessons learned from the Edelman and Boling data. AB - Because changes in the plasma water sodium concentration ([Na(+)]pw) are clinically due to changes in the mass balance of Na(+), K(+), and H2O, the analysis and treatment of the dysnatremias are dependent on the validity of the Edelman equation in defining the quantitative interrelationship between the [Na(+)]pw and the total exchangeable sodium (Nae), total exchangeable potassium (Ke), and total body water (TBW) (Edelman IS, Leibman J, O'Meara MP, Birkenfeld LW. J Clin Invest 37: 1236-1256, 1958): [Na(+)]pw = 1.11(Nae + Ke)/TBW - 25.6. The interrelationship between [Na(+)]pw and Nae, Ke, and TBW in the Edelman equation is empirically determined by accounting for measurement errors in all of these variables. In contrast, linear regression analysis of the same data set using [Na(+)]pw as the dependent variable yields the following equation: [Na(+)]pw = 0.93(Nae + Ke)/TBW + 1.37. Moreover, based on the study by Boling et al. (Boling EA, Lipkind JB. 18: 943-949, 1963), the [Na(+)]pw is related to the Nae, Ke, and TBW by the following linear regression equation: [Na(+)]pw = 0.487(Nae + Ke)/TBW + 71.54. The disparities between the slope and y-intercept of these three equations are unknown. In this mathematical analysis, we demonstrate that the disparities between the slope and y-intercept in these three equations can be explained by how the osmotically inactive Na(+) and K(+) storage pool is quantitatively accounted for. Our analysis also indicates that the osmotically inactive Na(+) and K(+) storage pool is dynamically regulated and that changes in the [Na(+)]pw can be predicted based on changes in the Nae, Ke, and TBW despite dynamic changes in the osmotically inactive Na(+) and K(+) storage pool. PMID- 27279488 TI - BIG: a large-scale data integration tool for renal physiology. AB - Due to recent advances in high-throughput techniques, we and others have generated multiple proteomic and transcriptomic databases to describe and quantify gene expression, protein abundance, or cellular signaling on the scale of the whole genome/proteome in kidney cells. The existence of so much data from diverse sources raises the following question: "How can researchers find information efficiently for a given gene product over all of these data sets without searching each data set individually?" This is the type of problem that has motivated the "Big-Data" revolution in Data Science, which has driven progress in fields such as marketing. Here we present an online Big-Data tool called BIG (Biological Information Gatherer) that allows users to submit a single online query to obtain all relevant information from all indexed databases. BIG is accessible at http://big.nhlbi.nih.gov/. PMID- 27279487 TI - The NHERF1 PDZ1 domain and IRBIT interact and mediate the activation of Na+/H+ exchanger 3 by ANG II. AB - Na(+)/H(+) exchanger (NHE)3, a major Na(+) transporter in the luminal membrane of the proximal tubule, is subject to ANG II regulation in renal Na(+)/fluid absorption and blood pressure control. We have previously shown that inositol 1,4,5-trisphosphate receptor-binding protein released with inositol 1,4,5 trisphosphate (IRBIT) mediates ANG II-induced exocytosis of NHE3 in cultured proximal tubule epithelial cells. In searching for scaffold protein(s) that coordinates with IRBIT in NHE3 trafficking, we found that NHE regulatory factor (NHERF)1, NHE3, and IRBIT proteins were coexpressed in the same macrocomplexes and that loss of ANG II type 1 receptors decreased their expression in the renal brush-border membrane. We found that NHERF1 was required for ANG II-mediated forward trafficking and activation of NHE3 in cultured cells. ANG II induced a concomitant increase of NHERF1 interactions with NHE3 and IRBIT, which were abolished when the NHERF1 PDZ1 domain was removed. Overexpression of a yellow fluorescent protein-NHERF1 construct that lacks PDZ1, but not PDZ2, failed to exaggerate the ANG II-dependent increase of NHE3 expression in the apical membrane. Moreover, exogenous expression of PDZ1 exerted a dominant negative effect on NHE3 activation by ANG II. We further demonstrated that IRBIT was indispensable for the ANG II-provoked increase in NHERF1-NHE3 interactions and that phosphorylation of IRBIT at Ser(68) was necessary for the assembly of the NHEF1-IRBIT-NHE3 complex. Taken together, our findings suggest that NHERF1 mediates ANG II-induced activation of renal NHE3, which requires coordination between IRBIT and the NHERF1 PDZ1 domain in binding and transporting NHE3. PMID- 27279489 TI - Wnt6: another player in the yin and yang of renal Wnt signaling. PMID- 27279490 TI - Prediction of renal crystalline size distributions in space using a PBE analytic model. 1. Effect of microgravity-induced biochemical alterations. AB - An analytical Population Balance Equation model is developed and used to assess the risk of critical renal stone formation for astronauts during future space missions. The model uses the renal biochemical profile of the subject as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating calcium oxalate crystals during their transit through the kidney. The model is verified through comparison with published results of several crystallization experiments. Numerical results indicate that the model is successful in clearly distinguishing between 1-G normal and 1-G recurrent stone former subjects based solely on their published 24-h urine biochemical profiles. Numerical case studies further show that the predicted renal calculi size distribution for a microgravity astronaut is closer to that of a recurrent stone former on Earth rather than to a normal subject in 1 G. This interestingly implies that the increase in renal stone risk level in microgravity is relatively more significant for a normal person than a stone former. However, numerical predictions still underscore that the stone-former subject carries by far the highest absolute risk of critical stone formation during space travel. PMID- 27279491 TI - Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures. AB - An analytic Population Balance Equation model is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal ground-based urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures. PMID- 27279493 TI - Magnetically recyclable Bi/Fe-based hierarchical nanostructures via self-assembly for environmental decontamination. AB - Pristine bismuth ferrite usually possesses weak magnetic properties (e.g., saturation magnetization Ms < 3 emu g(-1)) for practical magnetic separation applications. Herein, a superparamagnetic bismuth ferrite with coral-like hierarchical morphology (BFO-M) was fabricated through methanol solvothermal treatment of the as-prepared Bi2Fe4O9 nanoclusters (P-BFO). The BFO-M shows a higher Ms of ~31 emu g(-1) compared to that of P-BFO treated in water (BFO-A), in ethanol (BFO-E) and in ethylene glycol (BFO-G). Compared to single-crystalline Bi2Fe4O9 (PS) and Bi2Fe4O9 clusters (NSP), BFO-M shows an excellent organic pollutant removal rate by virtue of its high adsorption capacity and catalytic activity when methyl orange (MO) is used as the model organic pollutant. BFO-M also exhibits good visible light photo-Fenton oxidation rates for pharmaceuticals and pesticides. Even at a low catalyst loading of 0.12 g L(-1), the removal rate of organic pollutants (e.g., 5-fluorouracil, isoproturon) can be ~99% in 100 min under visible light irradiation. Besides, BFO-M is also a good adsorbent for different kinds of heavy metal ions (Pb(ii), Cr(iii), Cu(ii), As(v), etc.). For example, its maximal adsorption capacity for Pb(ii) is 214.5 mg g(-1). The used BFO-M can be recovered via magnetic separation. The outstanding performances of BFO-M can be ascribed to its coral-like hierarchical morphology which consists of the self-assembly of 1D nanowires (~6 nm in diameter) and 2D ultrathin nanoflakes (~4.5 nm in thickness). A schematic illustration of its morphology formation is proposed. PMID- 27279492 TI - Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats. AB - Immune cells in the kidney are implicated in the development of hypertension and renal damage in the Dahl salt-sensitive (SS) rat. Interestingly, interleukin 6 (IL-6) mRNA is 54-fold higher in T-lymphocytes isolated from the kidney compared with circulating T-lymphocytes. The present experiments assessed the role of IL-6 in the development of SS hypertension by treating rats (n = 13-14/group) with an IL-6 neutralizing antibody or normal IgG during an 11-day period of high-salt (4.0% NaCl chow) intake. The mean arterial pressure (MAP) and urine albumin excretion rates (Ualb) were not different between the groups fed low salt (0.4% NaCl). Following 11 days of drug treatment and high salt, however, the rats receiving anti-IL-6 demonstrated a 47% reduction of IL-6 in the renal medulla compared with control SS. Moreover, the increase in MAP following 11 days of high NaCl intake was significantly attenuated in SS administered anti-IL-6 compared with the control group (138 +/- 3 vs. 149 +/- 3 mmHg) as was the salt-induced increase in Ualb and glomerular and tubular damage. To investigate potential mechanisms of action, a flow cytometric analysis of immune cells in the kidney (n = 8-9/group) demonstrated that the total number of monocytes and macrophages was significantly lower in the treatment vs. the control group. The total number of T and B-lymphocytes in the kidneys was not different between groups. These studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating increased infiltration or proliferation of macrophages into the kidney. PMID- 27279494 TI - Molecular docking studies of Traditional Chinese Medicinal compounds against known protein targets to treat non-small cell lung carcinomas. AB - In silico drug design using virtual screening, absorption, distribution, metabolism and excretion (ADME)/Tox data analysis, automated docking and molecular dynamics simulations for the determination of lead compounds for further in vitro analysis is a cost effective strategy. The present study used this strategy to discover novel lead compounds from an in-house database of Traditional Chinese Medicinal (TCM) compounds against epithelial growth factor receptor (EGFR) protein for targeting non-small cell lung cancer (NSCLC). After virtual screening of an initial dataset of 2,242 TCM compounds, leads were identified based on binding energy and ADME/Tox data and subjected to automated docking followed by molecular dynamics simulation. Triptolide, a top compound identified by this vigorous in silico screening, was then tested in vitro on the H2347 cell line carrying wild-type EGFR, revealing an anti-proliferative potency similar to that of known drugs against NSCLC. PMID- 27279495 TI - Robot-Assisted Laparoscopic Excision of Ureteral and Ureteropelvic Junction Fibroepithelial Polyps in Children. AB - INTRODUCTION: Fibroepithelial polyps of the ureter are a rare cause of asymptomatic and symptomatic upper urinary tract obstruction in children. While these lesions can often be managed endoscopically, large or multifocal polyps may preclude such an approach. OBJECTIVE: We aim to describe our institutional experience with robot-assisted laparoscopic treatment of ureteral polyps and show that a robotic approach is an effective alternative for large or multifocal polyps. MATERIALS AND METHODS: Four children were identified with ureteral polyps over a 5-year period and underwent transperitoneal robot-assisted laparoscopic excision. Patients presented with flank pain and/or worsening hydronephrosis. All patients were evaluated preoperatively with ultrasound and Tc99m mercaptoacetyltriglycine (MAG3) diuretic renogram or MR urogram. Retrograde pyelography corroborated the diagnosis of ureteral polyps. We reviewed the charts of these patients and compared the specific robotic approach for each patient, length of hospitalization, surgical complications, need for additional procedures, and resolution of symptoms and hydronephrosis. RESULTS: In one patient, more than 20 polyps were identified over a long ureteral segment and all were excised; for the remaining three patients, 1 to 2 polyps were found. Mean postoperative length of stay was 1.5 days. One patient developed a ureteral stricture requiring repeat ureteroureterostomy, and another patient required repeat retrograde pyelography for gross hematuria that occurred several months after surgery. No polyps or obstruction was observed on retrograde pyelography in these patients. Mean duration of follow-up was 29 months (9-62 months). Symptoms and degree of hydronephrosis have improved in the three patients who have been followed for at least 12 months. CONCLUSIONS: Robot-assisted laparoscopy is a safe and feasible alternative to endoscopic treatment of fibroepithelial ureteral polyps. The robotic platform may be preferred in cases of multifocal or large ureteral polyps, or in cases in which a concomitant ureteropelvic junction narrowing may be present. PMID- 27279496 TI - Long-term outcomes of lung transplant recipients with hepatitis C infection: a retrospective study of the U.S. transplant registry. AB - BACKGROUND: Chronic hepatitis C patients in need of a lung transplant are often considered ineligible due to their infection. AIM: To assess the association of hepatitis C virus (HCV) infection with long-term outcomes of lung transplants. METHODS: From the Scientific Registry of Transplant Recipients (1995-2011), we selected all adults with and without HCV infection who underwent lung transplantation. RESULTS: A total of 17 762 lung transplant recipients were included (55.5% bilateral). Of those, 319 (1.83%) had positive HCV serology. The HCV-positive recipients were 1.6 years younger, less Caucasian and more African American, and had a significantly higher rate of co-infection with hepatitis B virus (all P < 0.001). Post-transplant patients were discharged alive at similar rates regardless of HCV status: 88.4% in HCV+ vs. 90.3% in HCV- (P = 0.25). The mortality rates were also similar at 1 and 2 years after transplantation (20.7% in HCV+ vs. 19.2% in HCV- and 31.6% in HCV+ vs. 28.9% in HCV-, respectively; both P > 0.05), but at post-transplant year 3 year, mortality rate in HCV+ became significantly higher (42.5% vs. 36.4%, P = 0.04) and remained higher for the duration of the follow-up (mean 9.1 years, max 18.4 years). In multivariate survival analysis, after adjustment for confounders, being HCV+ was associated with higher mortality: adjusted hazard ratio 1.24 (1.04-1.46), P = 0.01. No association of HCV infection with time to graft loss was found (P = 0.92). CONCLUSIONS: Chronic HCV infection is associated with a moderate increase in post lung transplant mortality. Treatment of HCV in lung transplant recipients may, therefore, result in improvement of post-transplant outcomes. PMID- 27279497 TI - Elucidation of the molecular mechanisms of two nanobodies that inhibit thrombin activatable fibrinolysis inhibitor activation and activated thrombin-activatable fibrinolysis inhibitor activity. AB - Essentials Thrombin-activatable fibrinolysis inhibitor (TAFI) is a risk factor for cardiovascular disorders. TAFI inhibitory nanobodies represent a promising step in developing profibrinolytic therapeutics. We have solved three crystal structures of TAFI in complex with inhibitory nanobodies. Nanobodies inhibit TAFI through distinct mechanisms and represent novel profibrinolytic leads. SUMMARY: Background Thrombin-activatable fibrinolysis inhibitor (TAFI) is converted to activated TAFI (TAFIa) by thrombin, plasmin, or the thrombin-thrombomodulin complex (T/TM). TAFIa is antifibrinolytic, and high levels of TAFIa are associated with an increased risk for cardiovascular disorders. TAFI-inhibitory nanobodies represent a promising approach for developing profibrinolytic therapeutics. Objective To elucidate the molecular mechanisms of inhibition of TAFI activation and TAFIa activity by nanobodies with the use of X-ray crystallography and biochemical characterization. Methods and results We selected two nanobodies for cocrystallization with TAFI. VHH-a204 interferes with all TAFI activation modes, whereas VHH-i83 interferes with T/TM-mediated activation and also inhibits TAFIa activity. The 3.05-A-resolution crystal structure of TAFI-VHH a204 reveals that the VHH-a204 epitope is localized to the catalytic moiety (CM) in close proximity to the TAFI activation site at Arg92, indicating that VHH-a204 inhibits TAFI activation by steric hindrance. The 2.85-A-resolution crystal structure of TAFI-VHH-i83 reveals that the VHH-i83 epitope is located close to the presumptive thrombomodulin-binding site in the activation peptide (AP). The structure and supporting biochemical assays suggest that VHH-i83 inhibits TAFIa by bridging the AP to the CM following TAFI activation. In addition, the 3.00-A resolution crystal structure of the triple TAFI-VHH-a204-VHH-i83 complex demonstrates that the two nanobodies can simultaneously bind to TAFI. Conclusions This study provides detailed insights into the molecular mechanisms of TAFI inhibition, and reveals a novel mode of TAFIa inhibition. VHH-a204 and VHH-i83 merit further evaluation as potential profibrinolytic therapeutics. PMID- 27279499 TI - Thermomechanical coupling in coarse grained cholesteric liquid crystal model systems with pitches of realistic length. AB - Thermomechanical coupling in cholesteric liquid crystals, i.e. when a temperature gradient parallel to the cholesteric axis rotates the director, has been studied in a model system of soft ellipsoids where the interaction potential has been augmented by a chiral potential. More specifically, the cross coupling coefficient between the temperature gradient and the director angular velocity, or Leslie coefficient, has been obtained as a function of the pitch by evaluating the corresponding Green-Kubo relation by molecular dynamics simulation. The product of the Leslie coefficient and the pitch has been found to be constant within the statistical uncertainty. This is in accordance with a symmetry condition originally proposed by de Gennes and it means that the Leslie coefficient of systems with longer pitches can be obtained from systems with shorter pitches. Since the pitches of realistic systems are usually very long, it becomes possible to study thermomechanical coupling in these systems which otherwise would have required prohibitively long simulations. Since we also have obtained rather accurate data on the cross correlation function between the director angular velocity and the heat current density, it becomes possible to analyse the mechanism of thermomechanical coupling to some extent. PMID- 27279498 TI - Cross-talk between AMPK and EGFR dependent Signaling in Non-Small Cell Lung Cancer. AB - Lung cancers globally account for 12% of new cancer cases, 85% of these being Non Small Cell Lung Cancer (NSCLC). Therapies like erlotinib target the key player EGFR, which is mutated in about 10% of lung adenocarcinoma. However, drug insensitivity and resistance caused by second mutations in the EGFR or aberrant bypass signaling have evolved as a major challenge in controlling these tumors. Recently, AMPK activation was proposed to sensitize NSCLC cells against erlotinib treatment. However, the underlying mechanism is largely unknown. In this work we aim to unravel the interplay between 20 proteins that were previously associated with EGFR signaling and erlotinib drug sensitivity. The inferred network shows a high level of agreement with protein-protein interactions reported in STRING and HIPPIE databases. It is further experimentally validated with protein measurements. Moreover, predictions derived from our network model fairly agree with somatic mutations and gene expression data from primary lung adenocarcinoma. Altogether our results support the role of AMPK in EGFR signaling and drug sensitivity. PMID- 27279500 TI - Using Fourier Transform Near-Infrared Spectroscopy to Predict the Mechanical Properties of Thermally Modified Southern Pine Wood. AB - This study seeks to estimate the mechanical properties of thermally modified wood (TMW) by using near-infrared (NIR) spectroscopy to measure 80 samples in three point bending tests. Near-infrared spectra collected from the transverse, radial, and tangential sections of wood, coupled with chemometric techniques, were used to predict the mechanical properties of southern pine wood, from which NIR models were constructed based on partial least squares and corresponding cross validation. The coefficient of determination between NIR transverse section spectra, as well as two mechanical properties of wood samples, modulus of rupture (MOR) and modulus of elasticity (MOE), were above 0.92 and greater than values for other sections. Spectral data from the transverse sections were richer than data from other sections, and thus, a model based on transverse sections better predicts the mechanical properties of wood. A close relationship between the values for mechanical properties (MOE and MOR) and the NIR spectra of thermally modified southern pine wood can be demonstrated, which provides the potential to predict the mechanical properties of untreated and thermally modified wood. PMID- 27279501 TI - Corrigendum. AB - Mr. Richard J. George was misidentified as "Richard G. George" as the co-author of the work entitled, "Characterization of Archaeological Sediments Using Fourier Transform Infrared (FT-IR) and Portable X-ray Fluorescence (pXRF): An Application to Formative Period Pyro-Industrial Sites in Pacific Coastal Southern Chiapas, Mexico", by Hector Neff, Scott J. Bigney, Sachiko Sakai, Paul R. Burger, Timothy Garfin, Richard J. George, Brendan J. Culleton, and Douglas J. Kennett, [Applied Spectroscopy, January 2016, vol. 70(01): 110-127. doi: 10.1177/0003702815617124]. We apologize for the error. PMID- 27279502 TI - High Surface-Enhanced Raman Scattering (SERS) Amplification Factor Obtained with Silver Printed Circuit Boards and the Influence of Phenolic Resins for the Characterization of the Pesticide Thiram. AB - In this work, low-cost substrates with rough silver surfaces were prepared from commercial copper foil-covered phenolic board (CPB) and an aqueous solution of AgNO3, and were used for surface-enhanced Raman scattering (SERS) and surface enhanced resonance Raman scattering (SERRS) measurements. A maximum SERS amplification factor of 1.2 * 10(7) was obtained for Rhodamine 6G (R6G), and use of the CPB resulted in a detection limit for Thiram pesticide of 0.5 umol L(-1) The minimum detection level was limited by residual traces of phenolic groups that originated from the substrate resin, which became solubilized in the aqueous Ag(+) solution. It was found that the bands corresponding to the impurities had less influence in the Thiram analysis, which could be explained by the high affinity of sulfur for Ag surfaces. The influence of impurities in the SERS analyses therefore depended on the linkage between the rough silver surface and the analyte. The findings demonstrated the ease and effectiveness of using CPB to prepare a nanostructured surface for SERS. PMID- 27279503 TI - Raman Gas Analyzer (RGA): Natural Gas Measurements. AB - In the present work, an improved model of the Raman gas analyzer (RGA) of natural gas (NG) developed by us is described together with its operating principle. The sensitivity has been improved and the number of measurable gases has been expanded. Results of its approbation on a real NG sample are presented for different measurement times. A comparison of the data obtained with the results of chromatographic analysis demonstrates their good agreement. The time stability of the results obtained using this model is analyzed. It is experimentally established that the given RGA can reliably determine the content of all molecular NG components whose content exceeds 0.005% for 100 s; moreover, in this case the limiting sensitivity for some NG components is equal to 0.002%. PMID- 27279504 TI - Micro-Raman Spectroscopy for the Determination of Local Temperature Increases in TiO2 Thin Films due to the Effect of Radiation. AB - This study applied a classic method involving Raman spectroscopy and the use of Stokes and anti-Stokes peaks to measure the temperature of TiO2 thin films found in dye-sensitized solar cells (DSSCs). In addition, three mathematical formulae were used and analyzed to estimate the increase in temperature generated solely by the effect of the radiation. The tests and calculations performed showed an increase in the temperature of the TiO2 film. That is, the films were heated by the radiation they were exposed to. A temperature increase of up to 30 K was detected for the sample with a single layer of TiO2, and over 40 K for the sample with three layers for the highest radiation powers used, and greater increases in temperature were observed in the thicker films. PMID- 27279505 TI - The potential role of microbes in oncogenesis with particular emphasis on oral cancer. AB - For over a century, non-virus microorganisms, notably bacteria have been implicated as causal agents of cancers, a relatively small number of researchers have provided evidence to support the so-called "cancer germ" hypothesis. With the exception of the link between Helicobacter pylori and stomach cancer, other supposed links have been ignored. A wide range of bacteria and other non-virus microbes, including fungi, have been implicated over the years in oncogenesis, as well as the ability to induce inflammation, which may cause cancer. It seems that there is no single "cancer germ," as most bacteria can apparently induce cancer. Here, the role of bacteria and other non-virus microorganisms and oral cancers will be discussed. By ignoring bacteria as a causal agent of cancer, we set back our understanding of this crucially important disease and, as a result, have hindered the development of potential cures. PMID- 27279506 TI - Comparison of medial versus lateral meniscus allograft transplantation. Literature review and meta-analysis. AB - OBJECTIVES: To perform a literature review and meta-analysis evaluating the effectiveness of medial and lateral meniscus allograft transplantation (MAT). METHODS: The literature review and meta-analysis were conducted between August and October 2015 in the People's Hospital of China Three Gorges University, Yi Chang, China. A systematic search was performed in the Medline and EMBASE databases, and the Cochrane Library for relevant literature published through October 2015. The outcomes of the included studies were analyzed in terms of the Lysholm Score, International Knee Documentation Committee (IKDC) Score, Knee Injury And Osteoarthritis Outcome Score (KOOS), Visual Analog Scale (VAS), Tegner Activity Score, MRI results, and failure rates. An adapted version of the Newcastle-Ottawa Scale was used for the methodological quality assessment in the meta-analyses. RESULTS: The literature review identified 12 observational studies, including 7 retrospective studies, 4 prospective studies, and the nature of one study was not reported. Significant differences in the outcomes of the lateral MAT group and the medial MAT group were observed in the IKDC scores, KOOS pain values, KOOS activities of daily living (ADL) values, and the absolute and relative extrusions observed on MRI, which suggested that the lateral MAT patients experienced superior clinical benefits compared with the medial MAT patients. However, significant differences between the lateral MAT group and the medial MAT group were not observed with regards to the Lysholm Scores, KOOS symptom values, KOOS sports and recreations values, KOOS quality of life (QOL) values, Tegner Activity Scores, VAS for pain values, and failure rates. CONCLUSION: The analysis results indicated that lateral MAT provides superior clinical outcomes compared with medial MAT according to the KOOS and IKDC scores. In addition, greater graft extrusion was observed in the medial group on MRI. Although significant differences were not detected between the 2 groups, the medial MAT patients were more prone to failure compared with the lateral MAT patients. PMID- 27279507 TI - Association of XRCC1 Trp194 allele with risk of breast cancer, and Ki67 protein status in breast tumor tissues. AB - OBJECTIVES: To evaluate the role of this polymorphism as a risk factor for breast cancer in Kurdish patients and to investigate the possible association between Arg194Trp x-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms with clinical and histopathological outcomes of patients with breast cancer. METHODS: A total of 100 breast cancer patients and 200 cancer-free controls in Kurdish population of Kurdistan state admitted to Tohid Hospital, Sanandaj, Kurdistan, Iran between January 2012 and May 2015 were enrolled in this cross sectional study. Tissue expression of estrogen receptor (ER), progesteron receptor (PR), human epidermal growth factor receptor 2 (Her2/neu), and Ki67 were evaluated by immunohistochemistry (IHC). The Arg194Trp genotypes were determined by polymerase chain reaction- restriction fragment length polymorphism method. RESULTS: Our data showed that the risk for breast cancer increased significantly among the Trp variant of XRCC1. Statistically significant association was found between codon 194 polymorphisms and tissue expression of Ki67. CONCLUSION: The Trp allele of codon 194 XRCC1 is a potential risk factor for breast cancer in Kurdish ethnicity. Furthermore, effect of this polymorphism on clinical and histological features of breast cancer was significant. PMID- 27279508 TI - Lung dose analysis in loco-regional hypofractionated radiotherapy of breast cancer. AB - OBJECTIVES: To report the ipsilateral lung dosimetry data of breast cancer (BC) patients treated with loco-regional hypofractionated radiotherapy (HFRT). METHODS: Treatment plans of 150 patients treated in the Radiotherapy Unit, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia between January 2012 and March 2015 by HFRT for BC were retrospectively reviewed. All patients received 42.4 Gy in 16 fractions by tangential and supra-clavicular fields with 6 MV, 18 MV, or mixed energies. Ipsilateral lung dosimetric data V20Gy and mean lung dose (MLD) were recorded. Correlations between lung dose, patient characteristics, and treatment delivery parameters were assessed by a logistic regression test. RESULTS: The mean ipsilateral lung V20Gy was 24.6% and mean MLD was 11.9 Gy. A weak, but statistically significant correlation was found between lung dose and lung volume (p=0.043). The lung dose was significantly decreasing with patient separation and depth of axillary lymph node (ALN) and supra claviculary lymph nodes (SCLN) (p less than 0.0001), and increasing with ALN (p=0.001) and SCLN (p=0.003) dose coverage. Lung dose significantly decreased with beam energy (p less than 0.0001): mean V20Gy was 27.8%, 25.4% for 6 MV, mixed energy, and 21.2% for 18 MV. The use of a low breast-board angle correlates with low lung dose. CONCLUSION: Our data suggest that the use of high energy photon beams and low breast-board angulation can reduce the lung dose. PMID- 27279509 TI - Costly coagulation profile tests prior to performing breast biopsies. Do we really need it? AB - OBJECTIVES: To reassess the need for routine coagulation profile testing in patients undergoing image-guided breast biopsies. METHODS: This is a retrospective cross-sectional study. Data was collected from the logbook of patients that underwent image-guided biopsies in the breast unit at the Department of Radiology, King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Patients' electronic records between November 2013 and October 2014 were included in the study. Exclusion criteria were those on anticoagulants, or platelet aggregation inhibitors, and patients with known primary, or secondary bleeding diathesis. The study was analyzed using the IBM Statistical Packages for Social Sciences Version 22 (IBMCorp, Armonk, NY, USA). RESULTS: A total of 136 patients were included in our study. Neither partial thromboplastin time (PTT), or thrombocytopenia was related to bleeding with p-values of 0.536 PTT and 0.997 thrombocytopenia. Needle gauge was found to be significantly related to bleeding episodes with a p=0.020. CONCLUSION: We advise against the routine use of coagulation profiles to predict bleeding risk. A thorough bleeding assessment is more advantageous. Laboratory tests should be tailored according to the patient's history and examination findings. PMID- 27279510 TI - Effects of hemodialysis on macular and retinal nerve fiber layer thicknesses in non-diabetic patients with end stage renal failure. AB - OBJECTIVES: To evaluate the thicknesses of retinal nerve fiber layer (RNFL) and macula by fourier-domain (FD) optical coherence tomography (OCT) in non-diabetic patients with end-stage-renal-failure (ESRF) undergoing hemodialysis (HD). METHODS: This is a prospective and observational study. Both eyes of 20 patients receiving HD (group 1) and 34 control patients (group 2) were evaluated by FD OCT. Macular and RNFL thicknesses were compared between groups and their correlation with age, duration of HD, and gender were examined. In group 1, macular and RNFL thicknesses were evaluated before and shortly after HD in the first day, first and sixth months. RESULTS: In group 1, pre-HD temporal, inferior, average RNFL thicknesses were thinner than group 2. This thinning did not correlate with duration of HD, age and gender. Pre-HD macular thicknesses were thinner than group 2. These thinnings did not correlate with age, but the thinnings at superior, nasal and average thickness correlated negatively with duration of HD. Nasal, temporal, and average macular thicknesses were thinner in female patients. The thickenings of RNFL and macula that were observed in the after HD first day and first month did not showed consistency in the sixth month except superior quadrant RNFL. CONCLUSION: Macular and RNFL thicknesses of patients receiving HD were less than the normal population. Age has no effect on these thinnings. The duration of HD affects more than gender. Hemodialysis session causes a consistent increase in superior quadrant RNFL. PMID- 27279511 TI - The analgesic efficacy of ultrasound-guided transversus abdominis plane block on postoperative pain and morphine consumption in varicocelectomy. AB - OBJECTIVES: To evaluate the analgesic effect of transversus abdominis plane (TAP) block administered before varicocele surgery. METHODS: This study was completed at the Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale, Turkey, between January 2011 and April 2013. In a prospective, double blind, randomized, placebo controlled clinical study, 40 male patients scheduled for elective varicocele operations were randomized to group T (treatment group) or group C (controls). After receiving general anesthesia, group T received a TAP block using 20 mL 0.25% bupivacaine on the operation side, whereas group C received a control block using 20 mL 0.9% Sodium chloride. During the first 24 hours after surgery, the patient pain was evaluated using the visual analogue scale (VAS) at rest and while coughing. Postoperative patient controlled analgesia morphine consumption, VAS scores, and side effects were recorded. RESULTS: Of 34 patients, Group T (n=18) had significantly lower VAS pain scores than Group C (n=16) both at rest and while coughing. The total morphine consumed was lower (7.7 +/- 4.0) versus 21.6 +/- 12.4 mg, p less than 0.001) in the 24 hours after surgery. CONCLUSION: As part of a multimodal analgesic regime after varicocelectomy surgery, morphine consumption and VAS pain scores were significantly lower among those receiving 20 mL 0.25% bupivacaine administered for a TAP block than among controls. PMID- 27279512 TI - Severe subtype of alopecia areata is highly associated with thyroid autoimmunity. AB - OBJECTIVES: To assess the significance of thyroid autoimmune screening in alopecia areata (AA) patients in Saudi population, and to determine whether there is a difference in thyroid autoimmune susceptibility between mild and severe AA. METHODS: In a prospective case-control study, we included 50 alopecia totalis (AT) and alopecia universalis (AU) patients, 50 age- and gender-matched patients with localized AA, and 50 age- and gender- matched healthy subjects between March 2015 and August 2015. Patients with AA were consecutively recruited from the hair disorders out-patient clinic of King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia. RESULTS: Thyroid autoantibodies (TAAs) were positive in AT/AU (40%), mild AA (14%), and healthy subjects (4%). The frequency of TAAs was significantly higher in patients with AT/AU than in mild AA (p=0.001) and healthy controls (p less than 0.001). The frequency of thyroid peroxidase antibody (TPO Abs) was significantly higher in patients with AT/AU than in mild AA and healthy controls (p less than 0.001 for both). The frequency of TG-Abs was significantly higher in patients with AT/AU (p=0.003) and mild AA (p=0.043) than in healthy controls. Serum TSH level was significantly higher in AT/AU patients than in mild AA patients (p=0.006) and healthy controls (p=0.005). CONCLUSION: Severe subtype of AA is associated with a high risk of autoimmune thyroid disease. This highlights the significance of screening for thyroid abnormalities and TAAs in patients with AT/AU. PMID- 27279513 TI - Suicide attempts and clinical features of bipolar patients. AB - OBJECTIVES: To identify clinical predictors of suicide attempts in patients with bipolar disorder. METHODS: This study included bipolar patients who were treated in the Psychiatry Department, Haseki Training and Research Hospital, Istanbul, Turkey, between 2013 and 2014; an informed consent was obtained from the participants. Two hundred and eighteen bipolar patients were assessed by using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) Axis-I (SCID-I) in order to detect all possible psychiatric comorbid diagnoses. Clinical predictors of suicide attempts were examined in attempters and non-attempters. The study design was retrospective. RESULTS: The lifetime suicide attempt rate for the entire sample was 19.2%. Suicide attempters with bipolar disorder had more lifetime comorbidity of eating disorder. Female gender and family history of mood disorder were significant predictors for suicide attempts. There was no difference between groups in terms of bipolar disorder subtype, onset age of bipolar disorder, total number of episodes, first and predominant episode type, suicide history in first degree relatives, severity of episodes, and hospitalization and being psychotic. CONCLUSION: Our study revealed that female gender, family history of mood disorder, and eating disorder are more frequent in bipolar patients with at least one suicide attempt. PMID- 27279514 TI - Validity and reliability of an Arabic version of the state-trait anxiety inventory in a Saudi dental setting. AB - OBJECTIVES: To test the psychometric properties of an adapted Arabic version of the state trait anxiety-form Y (STAI-Y) in Saudi adult dental patients. METHODS: In this cross-sectional study, the published Arabic version of the STAI-Y was evaluated by 2 experienced bilingual professionals for its compatibility with Saudi culture and revised prior to testing. Three hundred and eighty-seven patients attending dental clinics for treatment at the Faculty of Dentistry Hospital, King Abdullah University, Jeddah, Kingdom of Saudi Arabia, participated in the study. The Arabic version of the modified dental anxiety scale (MDAS) and visual analogue scale (VAS) ratings of anxiety were used to assess the concurrent criterion validity. RESULTS: The Arabic version of the STAI-Y had high internal consistency reliability (Cronbach's alpha: 0.989) for state and trait subscales. Factor analysis indicated unidimensionality of the scale. Correlations between STAI-Y scores and both MDAS and VAS scores indicated strong concurrent criterion validity. Discriminant validity was supported by the findings that higher anxiety levels were present among females as opposed to males, younger individuals as compared to older individuals, and patients who do not visit the dentist unless they have a need as opposed to more frequent visitors to the dental office. CONCLUSION: The Arabic version of the STAI-Y has an adequate internal consistency reliability, generally similar to that reported in the international literature, suggesting it is appropriate for assessing dental anxiety in Arabic speaking populations. PMID- 27279515 TI - Smartphone addiction among university students in Riyadh, Saudi Arabia. AB - OBJECTIVES: To investigate the prevalence and correlates of smartphone addiction among university students in Saudi Arabia. METHODS: This cross-sectional study was conducted in King Saud University, Riyadh, Kingdom of Saudi Arabia between September 2014 and March 2015. An electronic self administered questionnaire and the problematic use of mobile phones (PUMP) Scale were used. RESULTS: Out of 2367 study subjects, 27.2% stated that they spent more than 8 hours per day using their smartphones. Seventy-five percent used at least 4 applications per day, primarily for social networking and watching news. As a consequence of using the smartphones, at least 43% had decrease sleeping hours, and experienced a lack of energy the next day, 30% had a more unhealthy lifestyle (ate more fast food, gained weight, and exercised less), and 25% reported that their academic achievement been adversely affected. There are statistically significant positive relationships among the 4 study variables, consequences of smartphone use (negative lifestyle, poor academic achievement), number of hours per day spent using smartphones, years of study, and number of applications used, and the outcome variable score on the PUMP. The mean values of the PUMP scale were 60.8 with a median of 60. CONCLUSION: University students in Saudi Arabia are at risk of addiction to smartphones; a phenomenon that is associated with negative effects on sleep, levels of energy, eating habits, weight, exercise, and academic performance. PMID- 27279516 TI - Alveolar bone density and its clinical implication in the placement of dental implants and orthodontic mini-implants. AB - OBJECTIVES: To assess the bone density in maxilla and mandible in dentate and edentulous patients in Saudi population. METHODS: This study involved a retrospective analysis of cone beam CT images of 100 patients (50 male and 50 female) who have come to College of Dentistry, University of Dammam, Dammam, Kingdom of Saudi Arabia between January 2014 and 2015. Using the bone density option in the Simplant software, the Hounsfield unit (HU) was calculated at the edentulous sites. While for dentate sites, a region of interest was selected coronally at 3-5 mm to the root apex using I-CAT vision software. The densities of the buccal bone and cancellous bone were measured at interradicular areas of a specific teeth. RESULTS: The highest bone density at the edentulous sites was at the mandibular anterior region (776.5 +/- 65.7 HU), followed by the mandibular posterior region (502.2 +/- 224.2 HU). Regarding the dentate sites, the highest bone density was at the buccal cortical plate of the lower incisor teeth (937.56 +/- 176.92 HU) and the lowest bone density was at the cancellous bone around the posterior maxillary teeth (247.12 +/- 46.75 HU). CONCLUSION: The alveolar bone density at dentate and edentulous sites in our population is generally lower than the norm reference density of other populations, which dictates the need for quantitative assessment of bone density before implants and mini-implants placement. PMID- 27279517 TI - An eosinophilic variant granulomatosis with polyangiitis involving the dura, bilateral orbits, and mastoids. AB - Granulomatosis with polyangiitis (GPA) formerly called Wegener's granulomatosis is a chronic necrotizing granulomatous inflammatory disease with systemic vasculitis involving the upper and lower respiratory tract, and kidneys. The typical histopathology is that of necrotizing granulomatous inflammation with palisading histiocytes, neutrophils, and lymphocytes. We report a case of a 57 year-old lady presenting with left eye swelling, left ear pain and discharge, but with no pulmonary or renal symptoms. Investigations revealed positive cytoplasmic antineutrophil cytoplasmic antibodies and proteinase 3 antibodies. The CT and MRI showed meningeal thickening and bilateral structural changes of the orbits and mastoids. Lacrimal gland biopsy showed non necrotizing granulation with an eosinophilic infiltration. She was diagnosed with eosinophilic variant of GPA of the eyes and mastoid bones bilaterally extending to dura and sparing the lungs and kidneys. She responded to corticosteroids and rituximab. PMID- 27279518 TI - Spontaneous ileostomy closure. AB - Iatrogenic ileostomies are routinely placed during colorectal surgery for the diversion of intestinal contents to permit healing of the distal anastomosis prior to elective reversal. We present an interesting case of spontaneous closure of a diverting ileostomy without any adverse effects to the patient. A 65-year old woman, positive for hereditary non-polyposis colorectal cancer type-I, with locally invasive cancer of the distal colon underwent en-bloc total colectomy, hysterectomy, and bilateral salpingoophorectomy with creation of a proximal loop ileostomy. The ostomy temporarily closed without reoperation at 10 weeks, after spontaneously reopening, it definitively closed, again without surgical intervention at 18 weeks following the original surgery. This rare phenomenon has occurred following variable colorectal pathology and is poorly understood, particularly in patients with aggressive disease and adjunct perioperative interventions. PMID- 27279519 TI - Adequate iodine levels in healthy pregnant women. A cross-sectional survey of dietary intake in Turkey. AB - OBJECTIVES: To assess current iodine levels and related factors among healthy pregnant women. METHODS: In this cross-sectional, hospital-based study, healthy pregnant women (n=135) were scanned for thyroid volume, provided urine samples for urinary iodine concentration and completed a questionnaire including sociodemographic characteristics and dietary habits targeted for iodine consumption at the Department of Obstetrics and Gynecology, School of Medicine,Mugla Sitki Kocman University, Mugla, Turkey, between August 2014 and February 2015. Sociodemographic data were analyzed by simple descriptive statistics. RESULTS: Median urinary iodine concentration was 222.0 MUg/L, indicating adequate iodine intake during pregnancy. According to World Health Organization (WHO) criteria, 28.1% of subjects had iodine deficiency, 34.1% had adequate iodine intake, 34.8% had more than adequate iodine intake, and 3.0% had excessive iodine intake during pregnancy. Education level, higher monthly income, current employment, consuming iodized salt, and adding salt to food during, or after cooking were associated with higher urinary iodine concentration. CONCLUSION: Iodine status of healthy pregnant women was adequate, although the percentage of women with more than adequate iodine intake was higher than the reported literature. PMID- 27279520 TI - Investigation of parasitic and viral pathogens in mussels (Mytilus galloprovincialis) in the Gulf of Izmir, Turkey. AB - OBJECTIVES: To investigate Microsporidia spp. parasite, hepatitis A virus (HAV), and norovirus (NoV) contamination in mussels collected from 8 stations in the inner, middle, and outer regions of the Gulf of Izmir. METHODS: In this cross sectional study carried out between August 2009 and September 2010 in the Gulf of Izmir, Turkey, 15 mussels collected from each of the stations each season were pooled and homogenized to create a single representative sample. Thirty representative samples were available for analysis. Direct polymerase chain reaction (PCR), RT-nested PCR, and RT-booster PCR were used to investigate the pathogens. RESULTS: The mussels were negative for Microsporidia spp., but 8 (26.7%) samples analyzed were positive for HAV and 9 (30%) were positive for NoV. Excluding Foca and Gediz, viral contamination was detected in all of the stations sampled. CONCLUSION: Our results suggest that viral contamination is present in mussels in the Gulf of Izmir and may pose a potential threat to human health in the region. Necessary measures should be taken to prevent future illness due to these pathogens. PMID- 27279521 TI - Student research in Arab world. What is the current state? AB - [No Abstract Available]. PMID- 27279522 TI - A huge mass of the right adrenal in an elderly man. AB - [No Abstract Available]. PMID- 27279523 TI - Growth assessment and risk factors of malnutrition in children with cystic fibrosis. AB - [No Abstract Available]. PMID- 27279524 TI - Out of hospital adult cardiac arrests in a university hospital in Central Saudi Arabia. AB - [No Abstract available]. PMID- 27279525 TI - Ebola Virus Stability Under Hospital and Environmental Conditions. AB - The West African outbreak of Ebola virus (EBOV) is largely contained, but sporadic new cases continue to emerge. To assess the potential contribution of fomites to human infections with EBOV, we tested EBOV stability in human blood spotted onto Sierra Leonean banknotes and in syringe needles under hospital and environmental conditions. Under some of these conditions, EBOV remained infectious for >30 days, indicating that EBOV-contaminated items may pose a serious risk to humans. PMID- 27279526 TI - Sporozoite Route of Infection Influences In Vitro var Gene Transcription of Plasmodium falciparum Parasites From Controlled Human Infections. AB - BACKGROUND: Antigenic variation in Plasmodium falciparum is mediated by the multicopy var gene family. Each parasite possesses about 60 var genes, and switching between active var loci results in antigenic variation. In the current study, the effect of mosquito and host passage on in vitro var gene transcription was investigated. METHODS: Thirty malaria-naive individuals were inoculated by intradermal or intravenous injection with cryopreserved, isogenic NF54 P. falciparum sporozoites (PfSPZ) generated from 1 premosquito culture. Microscopic parasitemia developed in 22 individuals, and 21 in vitro cultures were established. The var gene transcript levels were determined in early and late postpatient cultures and in the premosquito culture. RESULTS: At the early time point, all cultures preferentially transcribed 8 subtelomeric var genes. Intradermal infections had higher var gene transcript levels than intravenous infections and a significantly longer intrahost replication time (P = .03). At the late time point, 9 subtelomeric and 8 central var genes were transcribed at the same levels in almost all cultures. Premosquito and late postpatient cultures transcribed the same subtelomeric and central var genes, except for var2csa CONCLUSIONS: The duration of intrahost replication influences in vitro var gene transcript patterns. Differences between premosquito and postpatient cultures decrease with prolonged in vitro growth. PMID- 27279527 TI - Biomechanical consequences of adding plantar fascia release to metatarsal osteotomies: Changes in forefoot plantar pressures. AB - Destruction of the normal metatarsal arch by a long metatarsal is often a cause for metatarsalgia. When surgery is warranted, distal oblique, or proximal dorsiflexion osteotomies of the long metatarsal bones are commonly used. The plantar fascia has anatomical connection to all metatarsal heads. There is controversial scientific evidence on the effect of plantar fascia release on forefoot biomechanics. In this cadaveric biomechanical study, we hypothesized that plantar fascia release would augment the plantar metatarsal pressure decreasing effects of two common second metatarsal osteotomy techniques. Six matched pairs of foot and ankle specimens were mounted on a pressure mat loading platform. Two randomly assigned surgery groups, which had received either distal oblique, or proximal dorsiflexion osteotomy of the second metatarsal, were evaluated before and after plantar fasciectomy. Specimens were loaded up to a ground reaction force of 400 N at varying Achilles tendon forces. Average pressures, peak pressures, and contact areas were analyzed. Supporting our hypothesis, average pressures under the second metatarsal during 600 N Achilles load were decreased by plantar fascia release following proximal osteotomy (p < 0.05). However contrary to our hypothesis, peak pressures under the second metatarsal were significantly increased by plantar fascia release following modified distal osteotomy, under multiple Achilles loading conditions (p < 0.05). Plantar fasciotomy should not be added to distal metatarsal osteotomy in the treatment of metatarsalgia. If proximal dorsiflexion osteotomy would be preferred, plantar fasciotomy should be approached cautiously not to disturb the forefoot biomechanics. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:800-804, 2017. PMID- 27279528 TI - The association between ruminative thinking and negative interpretation bias in social anxiety. AB - Cognitive models propose that both, negative interpretations of ambiguous social situations and ruminative thoughts about social events contribute to the maintenance of social anxiety disorder. It has further been postulated that ruminative thoughts fuel biased negative interpretations, however, evidence is rare. The present study used a multi-method approach to assess ruminative processing following a social interaction (post-event processing by self-report questionnaire and social rumination by experience sampling method) and negative interpretation bias (via two separate tasks) in a student sample (n = 51) screened for high (HSA) and low social anxiety (LSA). Results support the hypothesis that group differences in negative interpretations of ambiguous social situations in HSAs vs. LSAs are mediated by higher levels of post-event processing assessed in the questionnaire. Exploratory analyses highlight the potential role of comorbid depressive symptoms. The current findings help to advance the understanding of the association between two cognitive processes involved in social anxiety and stress the importance of ruminative post-event processing. PMID- 27279529 TI - An Introduction to the Psychopharmacology of Children and Adolescents With Autism Spectrum Disorder. AB - TOPIC: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that requires a multidisciplinary approach to treatment. Psychopharmacology can play an important role within an array of services to help children and adolescents with ASD. PURPOSE: This article reviews the current evidence supporting the use of various psychiatric medications to treat common symptoms that often compromise functioning: severe irritability, interfering repetitive behaviors, ADHD, anxiety, depression, and sleep dysregulation. Based on the accumulating research, the article also offers practice recommendations. SOURCES: The article primarily draws on the science generated by investigators from the Research Units on Pediatric Psychopharmacology Autism Network. This body of work consists of randomized controlled trials, meta-analyses, open trials, and review articles. CONCLUSIONS: There are currently no FDA-approved medications to treat the core symptoms of ASD. Consequently, all medications, besides risperidone and aripiprazole for severe irritability, are considered off-label. Additionally, due to reduced levels of effectiveness and higher rates of side effects, more typical medications such as antidepressants and stimulants should be used with caution. However, the evidence indicates that the thoughtful use of psychiatric medication in conjunction with other interventions may be beneficial in helping children and adolescents with ASD thrive at school and home. PMID- 27279530 TI - Downregulation of tetrahydrobiopterin inhibits tumor angiogenesis in BALB/c-nu mice with hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a highly vascular tumor, and treatment options for patients of advanced-stage are limited. Nitric oxide (NO), which is derived from endothelial nitric oxide synthase (eNOS), provides crucial signals for angiogenesis in the tumor microenvironment. Tetrahydrobiopterin (BH4) is an essential cofactor eNOS and represents a critical determinant of NO production. To examine whether treatment of 2,4-diamino-6-hydroxypyrimidine (DAHP) inhibits angiogenesis of HCC, BALB/c-nu mice were injected with HepG-2 cells with DAHP. Supplemental DAHP treatment decreased K-ras mRNA transcripts, inhibition of phosphorylation of eNOS and Akt, inhibition of guanosine triphosphate cyclohydrolase (GTPCH), and decreased significantly NO synthesis, and then inhibited angiogenesis, compared with the results observed in the saline group. Histopathology demonstrated angiogenesis and tumor formation were significantly inhibited in HCC. DAHP downregulates GTPCH protein expression, corresponding to decreased levels of BH4 and the contents of NO. In addition, DAHP downregulates eNOS and Akt protein expression, corresponding to decreased eNOS phosphorylation at Ser1177 and Akt phosphorylation, compared with the saline control. We suggest that DAHP, recognized as a specific competitive inhibitor of GTPCH, can decrease tumor BH4 and NO by the inhibition of the wild-type Ras-PI3K/Akt pathway, and then inhibiting angiogenesis, and may provide a novel and promising way to target BH4 synthetic pathways to inhibit angiogenesis and to control potential progression of HCC. Whether DAHP has a therapeutic potential will require more direct testing in humans. PMID- 27279531 TI - Poor prognostic value of lymphovascular invasion for pT1 urothelial carcinoma with squamous differentiation in bladder cancer. AB - Lymphovascular invasion (LVI) is the primary and essential step in the systemic dissemination of cancer cells. The aim of our study was to assess the independent prognostic role of LVI for pT1 urothelial carcinoma with squamous differentiation in bladder cancer. We retrospectively analyzed the clinical and pathological information of 206 patients diagnosed pT1 urothelial carcinoma with squamous differentiation. Of the 206 patients, LVI was detected in 57 (27.6%) patients. The 5 year cancer specific survival (CSS) rates were 87.2% in LVI (-) and 52.4% in LVI (+) (p < 0.001). According to univariate analysis, tumor multiplicity, tumor size, recurrence and LVI were the prognostic factors associated with CSS. Additionally, tumor size and LVI significantly influenced the CSS in multivariate analysis. TURBT had shorter median CSS than RC in recurred patients with LVI (+). Our study suggested that LVI is an important predictor for survival of pT1 urothelial carcinoma with squamous differentiation. LVI positive status and tumor size >=3 cm led to a higher risk of death. RC should be routinely performed in recurred LVI (+) bladder cancer patients of pT1 urothelial carcinoma with squamous differentiation. PMID- 27279532 TI - Bioactive Compounds, Chemical Composition, and Medicinal Value of the Giant Puffball, Calvatia gigantea (Higher Basidiomycetes), from Turkey. AB - In this study, the compositions of Calvatia gigantea were first analyzed in order to elucidate its chemical basis for development as a health-enhancing food or medicine. This study investigates the chemical composition (nutritional value; phenolic, sugar and fatty acid content; aroma compounds) and antioxidant properties (radical scavenging activity, reducing power, and inhibition of lipid peroxidation) of C. gigantea. The results showed that C. gigantea contains phenolic compounds and sugars and is rich in polyunsaturated fatty acids (67.93%), proteins (34.37%), and carbohydrates (51.97%). The most abundant compounds were gentisic acid (23.26 ug/g; as a phenolic compound), trehalose (9.78 g/100g; as a sugar), and hexanal (34.71%; as an aroma compound). These findings suggest that C. gigantea might be a promising source of medicine and has the potential to be a health food and food supplementary product. PMID- 27279533 TI - Protective Effect of Antioxidant Extracts from Grey Oyster Mushroom, Pleurotus pulmonarius (Agaricomycetes), Against Human Low-Density Lipoprotein Oxidation and Aortic Endothelial Cell Damage. AB - This study evaluated the in vitro antioxidant capacities of extracts from Pleurotus pulmonarius via Folin-Ciocalteu, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging, metal chelating, cupric ion reducing antioxidant capacity, and lipid peroxidation inhibition assays. Extract compositions were determined by phenol-sulfuric acid; Coomassie Plus (Bradford) protein; Spectroquant zinc, copper, and manganese test assays; and liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-mass spectrometry (GC/MS). Methanol-dichloromethane extract, water fraction, hot water, aqueous extract and hexane fraction exhibited the most potent extracts in the antioxidant activities. LC/MS/MS and GC/MS showed that the extracts contained ergothioneine, ergosterol, flavonoid, and phenolic compounds. The selected potent extracts were evaluated for their inhibitory effect against oxidation of human low-density lipoproteins and protective effects against hydrogen peroxide-induced cytotoxic injury in human aortic endothelial cells. The crude aqueous extract was deemed most potent for the prevention of human low-density lipoprotein oxidation and endothelial membrane damage. Ergothioneine might be the compound responsible for the activities, as supported by previous reports. Thus, P. pulmonarius may be a valuable antioxidant ingredient in functional foods or nutraceuticals. PMID- 27279534 TI - Royal Sun Medicinal Mushroom, Agaricus brasiliensis (Agaricomycetidae), Derived Polysaccharides Exert Immunomodulatory Activities In Vitro and In Vivo. AB - The royal sun mushroom, Agaricus brasiliensis is a widely consumed mushroom around the world. In this study, the immunoregulatory potential of A. brasiliensis polysaccharides was investigated in vitro and in vivo. In vivo, the polysaccharides remarkably increased the spleen and thymus indexes in mice, and this effect was influenced significantly by age (the adult and the juvenile). The spleen index increased by 27.28% in adult mice treated with the polysaccharides, whereas the increase in juvenile mice was just 12.59% at the dose of 150 mg.kg 1.d-1. Moreover, the effect of the polysaccharides on the thymus and spleen indexes in adult mice was obvious both in males and females. The carbon clearance ability (phagocytic index) was improved with increasing doses, (32.81% at 120 mg.kg-1.d-1, and 38.34% at 150 mg.kg-1.d-1) in mice treated with the polysaccharides. In vitro, the polysaccharides increased the RAW264.7 cell proliferation with 34.78% at 25 ug/mL and 26.78% at 50 ug/mL. Furthermore, the polysaccharides also promoted mRNA expressions of interleukin (IL)-6, IL-1beta, cyclooxygenase-2, and Toll-like receptor 4 (TLR4), myeloid differentiation 88 (MYD88), and TIR-domain-containing adapter-inducing interferon-beta (TRIF) in the cells, indicating that the polysaccharides induce the secretion of inflammatory cytokines by stimulating TLR4/MyD88 and TLR4/TRIF pathways. In conclusion, these results suggest that A. brasiliensis polysaccharides induce a very promising immunostimulation effect in vivo and in vitro. Therefore, it should be explored as a novel natural functional food additive. PMID- 27279535 TI - Antioxidant Potential of the Giant Mushroom, Macrocybe gigantea (Agaricomycetes), from India in Different Drying Methods. AB - Free radicals are responsible for several diseases like cancer, atherosclerosis, gastric ulcers, and several others. Studies have shown that mushrooms possess antioxidant activity and Macrocybe gigantea was recently added to the list of mushrooms under cultivation in India. The methanolic extracts were prepared from lyophilized and oven-dried samples of MA1 and MA2 strains of M. gigantea and their antioxidant properties were studied. MA2 showed comparatively higher total antioxidant activity (111.88 ug/mg) than MA1 (97.00 ug/mg). The scavenging activity on 2,2'-diphenyl picryl hydrazyl free radical (74.41%), ferrous chelating (83.74%), reducing power (0.371), and superoxide anion radical (72.05%) was significantly higher in freeze-dried MA2 than MA1 at 200 ug/mL. Correspondingly, the EC50 values were lower in freeze-dried states (96.03 ug/mL, 95.00 ug/mL, and 68.12 ug/mL in MA2 and 105.12 ug/mL, 109.8 ug/mL, and 74.60 ug/mL in MA1) than in oven-dried states (97.97 ug/mL, 120.2 ug/mL, and 125.33 ug/mL in MA2 and 108.3 ug/mL, 131.2 ug/mL, and 147.5 ug/mL in MA1, respectively). In addition, total phenolic, total flavonoid, and ortho-dihydroxy phenol content was examined and their values were comparatively higher in freeze-dried MA2 (18.00 mg/g of gallic acid equivalents, 1.67 mg/g of quercetin equivalents, and 1.10 mg/g of catechol equivalents, respectively) than in MA1 and oven-dried states in both strains. Further, MA2 showed lower EC50 values in freeze-dried samples than MA1 and oven-dried states in both strains. These results suggested that MA2 contains higher antioxidant potential than MA1 and freeze-drying by lyophilization retains higher antioxidants than heat drying by a hot air oven in both the strains; thus, they can be a good source of nutraceuticals. PMID- 27279537 TI - Determination of Zinc(II) Ions Released into Artificial Digestive Juices from Culinary-Medicinal Button Mushroom, Agaricus bisporus (Agaricomycetidae), Biomass of In Vitro Cultures Using an Anodic Stripping Voltammetry Method. AB - Zinc is one of those microelements that are essential for the proper functioning of the human body and must be supplemented in our food at a daily dose of 15 mg. It is well known that mushrooms accumulate elements; thus, in order to determine the extent of accumulation and the level of zinc released from mushrooms, in vitro cultures of Agaricus bisporus were established. The cultures were run on a modified Oddoux medium (a control culture) as well as on the same medium with the addition of zinc hydroaspartate (100 and 200 mg/L) and zinc sulfate (87.23 and 174.47 mg/L). These compounds were chosen to help estimate which form, organic or inorganic, results in a better assimilation of zinc(II) ions by biomass. As the next step, the level of zinc(II) ions released from the lyophilized biomass of in vitro cultures to the digestive juices, under thermal conditions of the human body (37 degrees C), was determined. For this purpose, artificial digestive juices, imitating the composition of human digestive juices, were used. For determination of zinc(II) ions in the digestive tract, an anodic stripping voltammetry method was employed. The amount of zinc released into artificial saliva over 1 minute varied from 0.15 mg/100 g d.w. in the control culture to 2.35 mg/100 g d.w. in the biomass in the medium to which 200 mg/L zinc hydroaspartate had been added. Values were higher in gastric juice and depended on incubation time (2.66 to 30.63 mg/100 g d.w.). In intestinal juice, the highest value of the released zinc grew to 24.20 mg/100 g d.w. (biomass of A. bisporus in vitro cultures in medium with the addition of 200 mg/L zinc hydroaspartate). Total average amount of zinc released into artificial digestive juices was the highest (56.26 mg/100 g d.w.) from A. bisporus biomass of in vitro cultures in the medium to which 200 mg/L zinc hydroaspartate had been added. PMID- 27279536 TI - Fractionation and Biological Activities of Water-Soluble Polysaccharides from Sclerotium of Tiger Milk Medicinal Mushroom, Lignosus rhinocerotis (Agaricomycetes). AB - This study investigated antioxidant and anti-inflammatory properties, and the direct cytotoxic effect of Lignosus rhinocerotis fractions, especially the polysaccharide fraction, on nasopharyngeal carcinoma cells. L. rhinocerotis crude extract was obtained through hot water extraction. The precipitate saturated with 30% ammonium sulfate was purified with ion-exchanged chromatography. Gel permeation chromatography multiangle laser light scattering analysis equipped with light scattering and UV signals revealed two district groups of polymers. A total of four peaks were observed in the total carbohydrate test. Fraction C, which was the second region of the second peak eluted with 0.3 M NaOH, showed the highest integrated molecular weight, whereas fraction E had the lowest integrated molecular weight of 19,790 Da. Fraction A contained the highest beta-D-glucan content. Enzymatic analysis showed that most of the polysaccharide fractions contained beta-1-3 and beta-1-6 skeletal backbones. The peak eluted with 0.6 M NaOH was separated in fraction D (flask 89-92) and fraction E (93-96). The results showed that fraction E expressed higher antioxidant activities than fraction D whereas fraction D expressed higher chelating activity than fraction E. The extract saturated with 30% ammonium sulfate exhibited higher reducing power than the extract saturated with 100% ammonium sulfate. Fractions D and E significantly inhibited the secretion of tumor necrosis factor-alpha in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. There was no apparent difference in the viability of cells exposed or unexposed to L. rhinocerotis fractions. PMID- 27279538 TI - Selection and Validation of Reference Genes for Quantitative Real-Time Polymerase Chain Reaction Studies in Mossy Maze Polypore, Cerrena unicolor (Higher Basidiomycetes). AB - With its ability to produce ligninolytic enzymes such as laccases, white-rot basidiomycete Cerrena unicolor, a medicinal mushroom, has great potential in biotechnology. Elucidation of the expression profiles of genes encoding ligninolytic enzymes are important for increasing their production. Quantitative real-time polymerase chain reaction (qPCR) is a powerful tool to study transcriptional regulation of genes of interest. To ensure accuracy and reliability of qPCR analysis of C. unicolor, expression levels of seven candidate reference genes were studied at different growth phases, under various induction conditions, and with a range of carbon/nitrogen ratios and carbon and nitrogen sources. The stability of the genes were analyzed with five statistical approaches, namely geNorm, NormFinder, BestKeeper, the DeltaCt method, and RefFinder. Our results indicated that the selection of reference genes varied with sample sets. A combination of four reference genes (Cyt-c, ATP6, TEF1, and beta-tubulin) were recommended for normalizing gene expression at different growth phases. GAPDH and Cyt-c were the appropriate reference genes under different induction conditions. ATP6 and TEF1 were most stable in fermentation media with various carbon/nitrogen ratios. In the fermentation media with various carbon or nitrogen sources, 18S rRNA and GAPDH were the references of choice. The present study represents the first validation analysis of reference genes in C. unicolor and serves as a foundation for its qPCR analysis. PMID- 27279539 TI - Screening of Indian Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes): A UPC2-SQD-MS Approach. AB - Oriental medicinal mushroom Ganoderma lucidum has been widely used for the promotion of health and longevity owing to its various bioactive constituents. Therefore, comprehending metabolomics of different G. lucidum parts could be of paramount importance for investigating their pharmacological properties. Ultra performance convergence chromatography (UPC2) along with mass spectrometry (MS) is an emerging technique that has not yet been applied for metabolite profiling of G. lucidum. This study has been undertaken to establish metabolomics of the aqueous extracts of mycelium (GLM), fruiting body (GLF), and their mixture (GLMF) using ultra-performance convergence chromatography single quadrupole mass spectrometry (UPC2-SQD-MS). Aqueous extracts of G. lucidum prepared using an accelerated solvent extraction technique have been characterized for their mycochemical activities in terms of total flavonoid content, 1,1-diphenyl-2 picryl-hydrazyl scavenging activity, and ferric ion reducing antioxidant power. The UPC2-SQD-MS technique has been used for the first time for metabolite profiling of G. lucidum on a Princeton Diol column (4.6 * 250 mm; 5 um) using supercritical CO2 (solvent) and 20 mM ammonium acetate in methanol (co-solvent). In the present study, UPC2-SQD-MS was found to be a rapid, efficient, and high throughput analytical technique, whose coupling to principal component analysis (PCA) and phytochemical evaluation could be used as a powerful tool for elucidating metabolite diversity between mycelium and fruiting body of G. lucidum. PCA showed a clear distinction in the metabolite compositions of the samples. Mycochemical studies revealed that overall GLF possessed better antioxidant properties among the aqueous extracts of G. lucidum. PMID- 27279540 TI - Active dynamics of colloidal particles in time-varying laser speckle patterns. AB - Colloidal particles immersed in a dynamic speckle pattern experience an optical force that fluctuates both in space and time. The resulting dynamics presents many interesting analogies with a broad class of non-equilibrium systems like: active colloids, self propelled microorganisms, transport in dynamical intracellular environments. Here we show that the use of a spatial light modulator allows to generate light fields that fluctuate with controllable space and time correlations and a prescribed average intensity profile. In particular we generate ring-shaped random patterns that can confine a colloidal particle over a quasi one-dimensional random energy landscape. We find a mean square displacement that is diffusive at both short and long times, while a superdiffusive or subdiffusive behavior is observed at intermediate times depending on the value of the speckles correlation time. We propose two alternative models for the mean square displacement in the two limiting cases of a short or long speckles correlation time. A simple interpolation formula is shown to account for the full phenomenology observed in the mean square displacement across the entire range from fast to slow fluctuating speckles. PMID- 27279542 TI - "Pigmentary incontinence" in the skin of the nasal plane from normal dogs? PMID- 27279541 TI - MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells. AB - The drug-resistance of pancreatic cancer cells results in poor therapeutic effect. To predict the therapeutic effect of the chemotherapy drugs to specific patients and to reverse the resistance of pancreatic cancer cells are critical for chemotherapy of pancreatic cancer. MicroRNAs (miRNAs) have been reported to play important roles in the genesis of drug-resistance of various cancer types. There are also many advantages of miRNAs in diagnosis and therapy of disease. Although several miRNAs regulating 5-Fluorouracil (5-FU) resistance in human pancreatic cancer have been reported, the detailed molecular mechanism remains to be determined. In this study, we found that miR-320a was significantly up regulated in 5-FU resistant pancreatic cancer cells. Over-expression of miR-320a strongly contributed to pathogenesis of pancreatic cancer, which was represented by the increased proliferation, invasion, metastasis, drug-resistance characteristics and the epithelial-to-mesenchymal transition. Furthermore, we demonstrated that miR-320a was able to bind to 3'UTR of PDCD4 mRNA, and mediated its down-regulation in 5-FU resistance of human pancreatic cancer cells. Whereas restoration of PDCD4 expression could partially attenuate the function of miR 320a in pancreatic cancer. Taken together, our study demonstrated that miR-320a played important role in regulating 5-FU resistance by targeting PDCD4 and might be developed as new therapeutic target for pancreatic cancer. PMID- 27279543 TI - New options in treatment of advanced renal cancer. PMID- 27279545 TI - Mn(2+) transport by Ca(2+) -ATPase of sarcoplasmic reticulum. AB - Ca(2+) -ATPase of sarcoplasmic reticulum is known to pump Mn(2+) in addition to Ca(2+) , but whether its transport mechanism is identical to that of Ca(2+) is ambiguous. To clarify, we examined, by atomic absorption spectroscopy, competition between Mn(2+) and Ca(2+) in active transport using vesicles of sarcoplasmic reticulum (SR). Here, we demonstrate that Ca(2+) -ATPase transports Ca(2+) and Mn(2+) concomitantly but has a much lower affinity for Mn(2+) (apparent Kd ~ 0.5 mm). Stoichiometries of transported ions per ATP hydrolysed, Vmax values and activation energies are very similar. Altogether, Ca(2+) -ATPase appears to use the same mechanism for transporting Mn(2+) as that for Ca(2+) . PMID- 27279544 TI - Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. AB - BACKGROUND: Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis. METHODS: In this open-label, randomised phase 3 trial, we randomly assigned (1:1) patients aged 18 years and older with advanced or metastatic clear-cell renal cell carcinoma, measurable disease, and previous treatment with one or more VEGFR tyrosine-kinase inhibitors to receive 60 mg cabozantinib once a day or 10 mg everolimus once a day. Randomisation was done with an interactive voice and web response system. Stratification factors were Memorial Sloan Kettering Cancer Center risk group and the number of previous treatments with VEGFR tyrosine-kinase inhibitors. The primary endpoint was progression-free survival as assessed by an independent radiology review committee in the first 375 randomly assigned patients and has been previously reported. Secondary endpoints were overall survival and objective response in all randomly assigned patients assessed by intention-to-treat. Safety was assessed per protocol in all patients who received at least one dose of study drug. The study is closed for enrolment but treatment and follow-up of patients is ongoing for long-term safety evaluation. This trial is registered with ClinicalTrials.gov, number NCT01865747. FINDINGS: Between Aug 8, 2013, and Nov 24, 2014, 658 patients were randomly assigned to receive cabozantinib (n=330) or everolimus (n=328). The median duration of follow-up for overall survival and safety was 18.7 months (IQR 16.1-21.1) in the cabozantinib group and 18.8 months (16.0-21.2) in the everolimus group. Median overall survival was 21.4 months (95% CI 18.7-not estimable) with cabozantinib and 16.5 months (14.7-18.8) with everolimus (hazard ratio [HR] 0.66 [95% CI 0.53-0.83]; p=0.00026). Cabozantinib treatment also resulted in improved progression-free survival (HR 0.51 [95% CI 0.41-0.62]; p<0.0001) and objective response (17% [13-22] with cabozantinib vs 3% [2-6] with everolimus; p<0.0001) per independent radiology review among all randomised patients. The most common grade 3 or 4 adverse events were hypertension (49 [15%] in the cabozantinib group vs 12 [4%] in the everolimus group), diarrhoea (43 [13%] vs 7 [2%]), fatigue (36 [11%] vs 24 [7%]), palmar plantar erythrodysaesthesia syndrome (27 [8%] vs 3 [1%]), anaemia (19 [6%] vs 53 [17%]), hyperglycaemia (3 [1%] vs 16 [5%]), and hypomagnesaemia (16 [5%] vs none). Serious adverse events grade 3 or worse occurred in 130 (39%) patients in the cabozantinib group and in 129 (40%) in the everolimus group. One treatment related death occurred in the cabozantinib group (death; not otherwise specified) and two occurred in the everolimus group (one aspergillus infection and one pneumonia aspiration). INTERPRETATION: Treatment with cabozantinib increased overall survival, delayed disease progression, and improved the objective response compared with everolimus. Based on these results, cabozantinib should be considered as a new standard-of-care treatment option for previously treated patients with advanced renal cell carcinoma. Patients should be monitored for adverse events that might require dose modifications. FUNDING: Exelixis Inc. PMID- 27279546 TI - Carbon nanotubes affect the toxicity of CuO nanoparticles to denitrification in marine sediments by altering cellular internalization of nanoparticle. AB - Denitrification is an important pathway for nitrate transformation in marine sediments, and this process has been observed to be negatively affected by engineered nanomaterials. However, previous studies only focused on the potential effect of a certain type of nanomaterial on microbial denitrification. Here we show that the toxicity of CuO nanoparticles (NPs) to denitrification in marine sediments is highly affected by the presence of carbon nanotubes (CNTs). It was found that the removal efficiency of total NOX(-)-N (NO3(-)-N and NO2(-)-N) in the presence of CuO NPs was only 62.3%, but it increased to 81.1% when CNTs appeared in this circumstance. Our data revealed that CuO NPs were more easily attached to CNTs rather than cell surface because of the lower energy barrier (3.5 versus 36.2 kT). Further studies confirmed that the presence of CNTs caused the formation of large, incompact, non-uniform dispersed, and more negatively charged CuO-CNTs heteroaggregates, and thus reduced the nanoparticle internalization by cells, leading to less toxicity to metabolism of carbon source, generation of reduction equivalent, and activities of nitrate reductase and nitrite reductase. These results indicate that assessing nanomaterial-induced risks in real circumstances needs to consider the "mixed" effects of nanomaterials. PMID- 27279547 TI - Autogenous demineralized dentin matrix from extracted tooth for the augmentation of alveolar bone defect: a prospective randomized clinical trial in comparison with anorganic bovine bone. AB - OBJECTIVES: The aim of this study was to prospectively evaluate the clinical efficacy and histological outcome of the autogenous tooth graft material (AutoBT) compared to that of anorganic bovine bone (Bio-Oss(r) , Geistlich, Switzerland) in post-extraction alveolar bone augmentation. PATIENTS AND METHODS: A total of 33 graft sites in 24 patients were included in this study. AutoBT was used in 21 sites of 15 patients and Bio-Oss(r) was used in 12 sites of 9 patients for alveolar bone augmentation 2-4 weeks after dental extraction. Vertical dimension of grafted bone was measured both at the time of graft placement and at implant fixture placement after 6 months. Trephine cores were harvested for the histomorphometric evaluations during implant placement when feasible. The primary stability of implant fixture was also measured. RESULTS: Infection of graft material or graft bed was not observed and graft sites healed without any notable complications in both groups. The vertical dimensions of alveolar bone increased by 5.38 +/- 2.65 mm in AutoBT group and 6.56 +/- 3.54 mm in Bio-Oss(r) group at 6 months post-extraction. Histomorphometrically, new bone formation of AutoBT grafted site was 31.24 +/- 13.87% while that of Bio-Oss(r) was 35.00 +/- 19.33%. The implant stability quotient (ISQ) of implants placed in AutoBT-grafted sites measured 72.80 +/- 10.81 while those placed in Bio-Oss(r) -grafted sites measured 70.0 +/- 12.86. There were no statistically significant differences between measurements of the two groups. CONCLUSION: Autogenous demineralized dentin matrix from extracted tooth grafted to extraction sockets for the augmentation of vertical dimension was as effective as augmentation using anorganic bovine bone. Both groups showed favorable wound healing, similar amount of implant stability, and histologically confirmed new bone formation. Thus, the results of this study suggest that autogenous tooth graft material is a viable option for alveolar bone augmentation following dental extraction. PMID- 27279548 TI - Omission of Hemostatic Agents During Robotic Partial Nephrectomy Does Not Increase Postoperative Bleeding Risk. AB - INTRODUCTION: The use of hemostatic agents (HA) during robotic partial nephrectomy (RPN) is largely empiric. We sought to assess the impact of HA on postoperative bleeding after RPN in a contemporary cohort. PATIENTS AND METHODS: Using our institutional RPN database, we identified consecutive patients treated between 2010 and 2015. HA were routinely placed in the nephrectomy bed at the time of renorrhaphy until 2014 when their use was phased out to reduce cost. We compared postoperative bleeding outcomes (blood transfusion and hemoglobin decline) between patients who did and did not receive HA, after excluding patients with preoperative anemia (hemoglobin <11 g/dL) or high estimated blood loss (>=175 mL). The total inflation-adjusted costs (for 2015) of HA were calculated. RESULTS: Of 544 cases, HA were used in 240 (44.1%). The mean number of agents per case was 1.4 +/- 0.73, including 77 (14.2%), 52 (9.6%), and 39 (7.2%) cases in which cellulose, fibrin, or gelatin-based agents were used alone, respectively, and 72 (13.2%) cases in which multiple agents were used. The mean cost of HA per case was $488 +/- 421. Nearly 90% of cases were performed by surgeons who were beyond their learning curves. Overall, 13 (2.4%) patients were transfused, and the median hemoglobin decline was 2.2 g/dL (IQR, 1.4-3.0 g/dL). On univariate analysis, HA use and type of HA were not significantly associated with blood transfusion (p = 0.20 and p = 0.29, respectively), but were associated with hemoglobin decline (p = 0.01 and p = 0.02, respectively). After adjusting for covariates, HA use was no longer significantly associated with postoperative hemoglobin decline. CONCLUSIONS: In nonanemic patients with minimal intraoperative bleeding, HA use does not alter postoperative bleeding outcomes after RPN, suggesting that their routine use in this setting merits reconsideration. Further research is needed to determine if HA may be useful in certain high-risk situations. PMID- 27279549 TI - Presbynasalis. AB - BACKGROUND: As with all systems in the body, the nose and paranasal sinuses change in time as we age. Some of these changes have been individually studied, but a unified description of current research has not been published since 1996. Since that time, a great deal has changed in our understanding of the aging nose. METHODS: The English language literature was examined using a combination of PubMed and Google Scholar search inquiries. The focus was on articles published since 1996 that described sinonasal changes or disease processes within the advanced-age population. RESULTS: Publications since 1996 were prioritized for discussion. Of the 50 articles selected, manuscripts were grouped into categories of allergy and cellular-level change, rhinorrhea, mechanical and airflow change, olfactory change, and sinusitis. CONCLUSION: Understanding the normal aging process is essential for otolaryngologists for patient education. We propose use of the term presbynasalis for description of the aging nose, paranasal sinuses, and olfactory system. Several points are consistent across the literature. The immune system becomes less responsive with age, a process known as immunosenescence. The incidence of rhinorrhea increases as the population ages. Though nasal volumes increase with age, other age-related changes may result in the perception of increasing nasal obstruction with age. There is a trend toward diminished olfaction in the elderly, and in some patients, this may be an early manifestation of neurodegenerative conditions. Sinusitis treatment should be similar in the elderly population, and the data demonstrates the safety of surgery when needed. PMID- 27279550 TI - Quality measures for anticoagulation care. AB - OBJECTIVE: To systematically identify and assess current quality measures for anticoagulation in atrial fibrillation (AF), venous thromboembolism (VTE) treatment and surgical VTE prophylaxis. RESEARCH DESIGN AND METHODS: Fifteen quality measure websites were searched as were bibliographic databases (January 2000-February 2016). Quality measures were included if developed in the United States and incorporating an aspect of anticoagulation for the aforementioned indications or if applicable but not indication specific (non-disease specific measure). Two reviewers independently extracted data regarding the characteristics of each quality measure. RESULTS: Thirty-five measures were identified, mostly in VTE treatment (48.6%), followed by non-disease specific measures (25.7%), AF (17.6%) and surgical VTE prophylaxis (8.8%). Process measures predominated (82.9%). A majority of quality measures (65.7%) were focused on parenteral anticoagulants or warfarin and not applicable to novel oral anticoagulants (NOACs). Ten (28.6%) measures are used by the Centers for Medicare and Medicaid Services or as a core measure of The Joint Commission. Limitations include the inability to statistically pool data and possible publication bias given the nature of databases for quality measures. CONCLUSIONS: Quality measures are recognized in anticoagulation care. Areas for improvement include expanding beyond process measures and capturing adverse events and the advantages offered by NOACs. PMID- 27279552 TI - Stakeholders' Perspectives towards the Use of the Comprehensive Health Assessment Program (CHAP) for Adults with Intellectual Disabilities in Manitoba. AB - BACKGROUND: No standardized tool is used in Canada for comprehensive health assessments of adults with intellectual disabilities. This study was conducted to determine the feasibility of implementing the Comprehensive Health Assessment Program (CHAP) in Manitoba, Canada. METHOD: This was a qualitative study using a purposive sample of physicians, nurse practitioners, support workers and families. Data were collected through individual interviews and focus groups and were analysed using content analysis. RESULTS: Use of the CHAP was perceived as beneficial for persons with intellectual disabilities. Improved continuity of care was of the reported benefits. Six barriers for the future implementation of the CHAP were identified including the time required to complete the CHAP, and the perceived lack of physicians' willingness to do comprehensive assessments. CONCLUSION: The future implementation of the CHAP was strongly supported. For its successful implementation, training of healthcare professionals and support staff and change in regulations and policies were recommended. PMID- 27279551 TI - Intraspecific phytochemical variation shapes community and population structure for specialist caterpillars. AB - Chemically mediated plant-herbivore interactions contribute to the diversity of terrestrial communities and the diversification of plants and insects. While our understanding of the processes affecting community structure and evolutionary diversification has grown, few studies have investigated how trait variation shapes genetic and species diversity simultaneously in a tropical ecosystem. We investigated secondary metabolite variation among subpopulations of a single plant species, Piper kelleyi (Piperaceae), using high-performance liquid chromatography (HPLC), to understand associations between plant phytochemistry and host-specialized caterpillars in the genus Eois (Geometridae: Larentiinae) and associated parasitoid wasps and flies. In addition, we used a genotyping-by sequencing approach to examine the genetic structure of one abundant caterpillar species, Eois encina, in relation to host phytochemical variation. We found substantive concentration differences among three major secondary metabolites, and these differences in chemistry predicted caterpillar and parasitoid community structure among host plant populations. Furthermore, E. encina populations located at high elevations were genetically different from other populations. They fed on plants containing high concentrations of prenylated benzoic acid. Thus, phytochemistry potentially shapes caterpillar and wasp community composition and geographic variation in species interactions, both of which can contribute to diversification of plants and insects. PMID- 27279553 TI - Molecular detection of Wolbachia pipientis in natural populations of mosquito vectors of Dirofilaria immitis from continental Portugal: first detection in Culex theileri. AB - Wolbachia pipientis (Rickettsiales: Rickettsiaceae) protects mosquitoes from infections with arboviruses and parasites. However, the effect of its co infection on vector competence for Dirofilaria immitis (Spirurida: Onchocercidae) in the wild has not been investigated. This study aimed to screen vectors of D. immitis for wPip, to characterize these, and to investigate a possible association between the occurrence of W. pipientis and that of the nematode. The presence of W. pipientis was assessed in the five mosquito potential vectors of D. immitis in Portugal. Polymerase chain reaction (PCR) products were sequenced, and wPip haplotypes were determined by PCR-restricted fragment length polymorphism (RFLP). Results showed that wPip was detected in 61.5% of Culex pipiens (Diptera: Culicidae) pools and 6.3% of Culex theileri pools. wPip 16s rRNA sequences found in Cx. theileri exactly match those from Cx. pipiens, confirming a mosquito origin, rather than a nematode origin, as some specimens were infected with D. immitis. Only wPip haplotype I was found. No association was found between the presence of wPip and D. immitis in mosquitoes and hence a role for this endosymbiont in influencing vectorial competence is yet to be identified. This study contributes to understanding of wPip distribution in mosquito populations and, to the best of the authors' knowledge, is the first report of natural infections by wPip in Cx. theileri. PMID- 27279554 TI - Do patients with intake of drugs labelled as sleep disturbing really sleep worse? A population based assessment from the Heinz Nixdorf Recall Study. AB - AIM: The sleep disturbing effect of many drugs is derived from clinical trials with highly selected patient collectives. However, the generalizability of such findings to the general population is questionable. Our aim was to assess the association between intake of drugs labelled as sleep disturbing and self reported nocturnal sleep disturbances in a population-based study. METHODS: We used data of 4221 participants (50.0% male) aged 45 to 75 years from the baseline examination of the Heinz Nixdorf Recall Study in Germany. The interview provided information on difficulties falling asleep, difficulties maintaining sleep and early morning arousal. We used the summary of product characteristics (SPC) for each drug taken and assigned the probability of sleep disturbances. Thereafter, we calculated cumulative probabilities of sleep disturbances per subject to account for polypharmacy. We estimated prevalence ratios (PR) using log Poisson regression models with robust variance. RESULTS: The adjusted PRs of any regular nocturnal sleep disorder per additional sleep disturbing drug were 1.01 (95% confidence interval (CI) 0.97, 1.06) and 1.03 (95% CI 1.00, 1.07) for men and women, respectively. Estimates for each regular nocturnal sleep disturbance were similarly close to 1. PRs for regular nocturnal sleep disturbances did not increase with rising cumulative probability for drug-related sleep disturbances. CONCLUSIONS: SPC-based probabilities of drug-related sleep disturbances showed barely any association with self-reported regular nocturnal sleep disturbances. We conclude that SPC-based probability information may lack generalizability to the general population or may be of limited data quality. PMID- 27279555 TI - TGF-beta1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway. AB - Hypertrophy of the ligamentum flavum (LF) is one of the key pathomechanisms of lumbar spinal stenosis (LSS). Transforming growth factor (TGF)-beta1 is abundantly expressed in hypertrophied degenerative LF tissues from LSS. However, the molecular mechanisms underling the association between TGF-beta1 and LF hypertrophy have not yet been fully elucidated. In this study, we investigated the important role of the mitogen-activated protein kinase (MAPK) pathway in the pathogenesis of LSS by analyzing the expression of connective tissue growth factor (CTGF) and extracellular matrix (ECM) components (collagen I and collagen III) in TGF-beta1-treated LF cells. Cell growth assay revealed that TGF-beta1, in association with CTGF, enhanced the the proliferation of LF cells, and we found that TGF-beta1 also elevated CTGF expression and subsequently enhanced the mRNA expression of collagen I and collagen III. The increased mRNA expression levels of CTGF, collagen I and collagen III were abolished by p38 inhibitors. Both immunofluorescence imaging and western blot analysis of p38 and p-p38 revealed the increased expression and phosphorylation of p38. Silencing the expression of p38 by siRNA in LF cells decreased the protein expression of p38, p-p38 and CTGF, as well as the mRNA expression of CTGF, collagen I and collagen III. Taken together, our findings indicate that TGF-beta1, in association with the increased expression of CTGF, contribute to the homeostasis of the ECM and to the hypertrophy of LF through the p38 MAPK pathway. PMID- 27279556 TI - Induction of adipose-derived stem cells into Schwann-like cells and observation of Schwann-like cell proliferation. AB - The peripheral nervous system has the potential for full regeneration following injury and recovery, predominantly controlled by Schwann cells (SCs). Therefore, obtaining a sufficient number of SCs in a short duration is crucial. In the present study, rat adipose-derived stem cells (ADSCs) were isolated and cultured, following which characterization of the ADSCs was performed using flow cytometry. The results showed that the cells were positive for the CD29 and CD44 markers, and negative for the CD31, CD45, CD49 and CD106 markers. The multilineage differentiation potential of the ADSCs was assayed by determining the ability of the cells to differentiate into osteoblasts and adipocytes. Following this, the ADSCs were treated with a specific medium and differentiated into Schwann-like cells. Immunofluorescence, western blot and reverse transcription-quantitative polymerase chain reaction analyses showed that ~95% of the differentiated cells expressed glial fibrillary acidic protein, S100 and p75. In addition, the present study found that a substantial number of SCs can be produced in a short duration via the mitotic feature of Schwann-like cells. These data indicated that Schwann like cells derived from ADSCs can undergo mitotic proliferation, which may be beneficial for the treatment of peripheral nerve injury in the future. PMID- 27279557 TI - Monitoring the quality consistency of Fufang Danshen Pills using micellar electrokinetic chromatography fingerprint coupled with prediction of antioxidant activity and chemometrics. AB - A fast micellar electrokinetic chromatography fingerprint method combined with quantification was developed and validated to evaluate the quality of Fufang Danshen Pills, a traditional Chinese Medicine, which has been used in the treatment of cardiovascular system diseases, in which the tetrahedron optimization method was first used to optimize the background electrolyte solution. Subsequently, the index of the fingerprint information amount of I was performed as an excellent objective indictor to investigate the experimental conditions. In addition, a systematical quantified fingerprint method was constructed for evaluating the quality consistency of 20 batches of test samples obtained from the same drug manufacturer. The fingerprint analysis combined with quantitative determination of two components showed that the quality consistency of the test samples was quite good within the same commercial brand. Furthermore, the partial least squares model analysis was used to explore the fingerprint efficacy relationship between active components and antioxidant activity in vitro, which can be applied for the assessment of anti-oxidant activity of Fufang Danshen pills and provide valuable medicinal information for quality control. The result illustrated that the present study provided a reliable and reasonable method for monitoring the quality consistency of Fufang Danshen pills. PMID- 27279558 TI - Motivations for Deceased Organ Donation Among Volunteers in China: A Qualitative Research Study. AB - BACKGROUND To align with guiding principles on human organ and tissue transplantation published by the World Health Organization (WHO), the Red Cross Society of China (RCSC) launched a new nationwide organ donation program in 2010 to recruit organ donation volunteers. Despite severe shortage of donated organs, there is a very low rate of volunteering for organ donation among the Chinese population (only 0.03 donors per million population) in the national program. Motivating organ donation is the key to the success of organ transplantation in China. MATERIAL AND METHODS Semi-structured 45- to 60-min interviews were conducted among 34 volunteers. Data analysis was performed with Nvivo 8.0 software. RESULTS Six motivations for organ donation were identified: helping others/altruism, fulfilling long-cherished wishes, reducing the burdens, making the best use of everything, giving back to society, and life extension. Factors affecting the motivation of organ donation among volunteers in China included traditional values, personal experiences, role model effect, family support, and problems in the donation system. Possible strategies to improve organ donation included fostering a scientific concept of the body and death, focusing donation promotion efforts on certain groups, and simplifying the process of organ donation. CONCLUSIONS There are multiple reasons for Chinese people to register for organ donation, with helping others as the central motivation. PMID- 27279559 TI - Visual analysis of data in a multielement design. AB - Ninety Board Certified Behavior Analysts (BCBAs) and 19 editorial board members evaluated hypothetical data presented in a multielement design. We manipulated the variability, trend, and mean shift of the data and asked the participants to determine if the data demonstrated experimental control. The results showed that variability, trend, and mean shift interacted to affect the participants' ratings of experimental control. The level of agreement between participants was variable, but was generally lower than in previous research. PMID- 27279560 TI - Kinesin family members KIF11 and KIF23 as potential therapeutic targets in malignant pleural mesothelioma. AB - Malignant pleural mesothelioma (MPM) is a rare and aggressive form of cancer commonly associated with asbestos exposure that stems from the thoracic mesothelium with high mortality rate. Currently, treatment options for MPM are limited, and new molecular targets for treatments are urgently needed. Using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and an RNA interference-based screening, we screened two kinesin family members as potential therapeutic targets for MPM. Following in vitro investigation of the target silencing effects on MPM cells, a total of 53 MPMs were analyzed immunohistochemically with tissue microarray. KIF11 and KIF23 transcripts were found to be overexpressed in the majority of clinical MPM samples as well as human MPM cell lines as determined by quantitative RT-PCR. Gene knockdown in MPM cell lines identified growth inhibition following knockdown of KIF11 and KIF23. High expression of KIF11 (KIF11-H) and KIF23 (KIF23-H) were found in 43.4 and 50.9% of all the MPM cases, respectively. Patients who received curative resection with tumors displaying KIF23-H showed shorter overall survival (P=0.0194). These results provide that inhibition of KIF11 and KIF23 may hold promise for treatment of MPMs, raising the possibility that kinesin-based drug targets may be developed in the future. PMID- 27279561 TI - Low Intensity Epicardial Pacing During the Absolute Refractory Period Augments Left Ventricular Function Mediated by Local Catecholamine Release. AB - BACKGROUND: Biventricular epicardial (Epi) pacing can augment left ventricular (LV) function in heart failure. We postulated that these effects might involve catecholamine release from local autonomic nerve activation. To evaluate this hypothesis we applied low intensity Epi electrical stimuli during the absolute refractory period (ARP), thus avoiding altered activation sequence. METHODS: Anesthetized pigs (n = 6) were instrumented with an LV pressure (LVP) transducer, left atrial (LA) and LV Epi pacing electrodes, and sonomicrometer segment length (SL) gauges placed proximal and remote to the LV stimulation site. A catheter was placed into the great cardiac vein adjacent to the LV pacing site for norepinephrine (NE) analysis. During LA pacing at constant rate, 3 pulses (0.8 milliseconds, 2-3x threshold) were applied to the LV Epi electrodes during the ARP. An experimental run consisted of baseline, stimulation (10 minutes), and recovery (5 minutes), repeated 3 times before and after beta1 - receptor blockade (BB, metoprolol). RESULTS: ARP stimulation produced significant increases in cardiac function reflected by elevated LVP, LV, dP/dtmax , and reduced time to LV dP/dtmax . This was accompanied by increased coronary NE levels and increases in LVP versus SL loop area in the remote myocardial segment. In contrast, the proximal segment exhibited early shortening and decreased loop area. BB abolished the changes in SL and LV function despite continued NE release. CONCLUSION: These results demonstrate that ARP EPI stimulation induces NE release mediating augmented global LV function. This effect may contribute to the beneficial effect of biventricular Epi pacing in heart failure in some patients. PMID- 27279562 TI - Application effect of sterile normal saline ice for post-partum hemorrhage at the time of cesarean delivery: A retrospective review. AB - AIM: Post-partum hemorrhage (PPH) is a common complication of cesarean sections (CS) and affects maternal and newborn health. We used a new method to control bleeding and compared its efficacy with conventional methods. METHODS: Eighty-six women who experienced PPH with volume of bleeding over 1000 mL in CS between January 2008 and January 2012 were chosen as samples. Thirty-three underwent the new method in which normal saline ice blocks are placed in the uterus, and 53 underwent the conventional method. We evaluated blood loss, volume of transfusion and complications. RESULTS: Patients who were treated with ice blocks had better hemostatic efficacy than those who underwent the conventional method (1450 +/- 251.9 mL vs 1800 +/- 278.9 mL; P < 0.001); they also had less blood transfusion (806.1 +/- 242.3 mL vs 1222.6 +/- 308.0 mL; P < 0.001), lower rate of hysterectomy and infection (3.03% vs 5.66%; P = 0.971; 0% vs 7.55%; P = 0.276), and shorter duration of hospital stay (5.3 +/- 0.5 days vs 7.6 +/- 3.0 days; P < 0.001). CONCLUSION: PPH in CS can be treated with peeled sterile normal saline ice blocks, a simple and reliable method for stopping bleeding. Nonetheless, there needs to be a large randomized control trial for confirmation. PMID- 27279563 TI - The application of crystallization in the presence of additives to enable drug-in capsule technology. AB - Crystallization in the presence of additives such as surfactants, polymers or impurities has been widely investigated in the pharmaceutical and chemical industries in order to change the crystal habit or to obtain a more desirable polymorph, affect crystal growth and influence dissolution. However, in this study, we investigated the concept of crystallization in the presence of surfactants in order to incorporate into the crystal lattice, a small amount (less than 1% w/w) of surfactant, sodium lauryl sulfate (SLS). The resulting crystals were further compared to crystals coated with SLS using a washing procedure; in order to assess whether either procedure generates improvements in the apparent solubility and dissolution of a poorly soluble drug so it can be filled directly into a capsule without the need of a complex formulation process. PMID- 27279564 TI - Foci of cyclin A2 interact with actin and RhoA in mitosis. AB - Cyclin A2 is a key player in the regulation of the cell cycle. Its degradation in mid-mitosis depends primarily on the ubiquitin-proteasome system (UPS), while autophagy also contributes. However, a fraction of cyclin A2 persists beyond metaphase. In this work, we focus on cyclin A2-rich foci detected in mitosis by high resolution imaging and analyse their movements. We demonstrate that cyclin A2 interacts with actin and RhoA during mitosis, and that cyclin A2 depletion induces a dramatic decrease in active RhoA in mitosis. Our data suggest cyclin A2 participation in RhoA activation in late mitosis. PMID- 27279565 TI - Optical control of filamentation-induced damage to DNA by intense, ultrashort, near-infrared laser pulses. AB - We report on damage to DNA in an aqueous medium induced by ultrashort pulses of intense laser light of 800 nm wavelength. Focusing of such pulses, using lenses of various focal lengths, induces plasma formation within the aqueous medium. Such plasma can have a spatial extent that is far in excess of the Rayleigh range. In the case of water, the resulting ionization and dissociation gives rise to in situ generation of low-energy electrons and OH-radicals. Interactions of these with plasmid DNA produce nicks in the DNA backbone: single strand breaks (SSBs) are induced as are, at higher laser intensities, double strand breaks (DSBs). Under physiological conditions, the latter are not readily amenable to repair. Systematic quantification of SSBs and DSBs at different values of incident laser energy and under different external focusing conditions reveals that damage occurs in two distinct regimes. Numerical aperture is the experimental handle that delineates the two regimes, permitting simple optical control over the extent of DNA damage. PMID- 27279566 TI - Identification and association of RAC1 gene polymorphisms with mRNA and protein expression levels of Rac1 in solid organ (kidney, liver, heart) transplant recipients. AB - The activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) is critical in the renal, hepatic and cardiac diseases that lead to the requirement for transplantation, however, no investigations have been performed in Chinese populations to determine the association between RAC1 genotypes and the activation of Rac1. In the present study, 304 solid organ transplant recipients (SOTRs), consisting of 164 renal transplantations, 85 hepatic transplantations and 55 cardiac transplantations, and 332 Chinese healthy control subjects were recruited to investigate whether differences existed in the mRNA and protein expression levels of Rac1 in the different groups. Furthermore, the present study identified and investigated associations of the RAC1 (rs702482, rs10951982, rs702483 and rs6954996) genotypes with the mRNA expression levels of RAC1, and the protein expression levels of total Rac1 and active Rac1-guanosine triphosphatase (GTP). It was identified that the healthy population had significantly higher levels of Rac1 and Rac1-GTP, compared with the kidney, liver and heart transplantation populations (P<0.001 for all comparisons). Significant associations (P<0.05) were observed between the RAC1 genotypes and the expression levels of mRNA, Rac1 and Rac1-GTP. However, the changes in the mRNA expression levels of RAC1 with genotypes were different from those of the proteins. The results of the present study represent the first, to the best of our knowledge, to report that Rac1 and Rac1-GTP proteins can be downregulated in SOTRs, and that RAC1 genetic polymorphisms can potentially affect the mRNA expression of RAC1, and the protein expression of Rac1 and Rac1-GTP. These results provide a foundation for further functional investigations to determine the biological and molecular functions of the RAC1 gene in SOTRs. PMID- 27279567 TI - The halotolerant Debaryomyces hansenii, the Cinderella of non-conventional yeasts. AB - Debaryomyces hansenii is a halotolerant yeast with a high biotechnological potential, particularly in the food industry. However, research in this yeast is limited by its molecular peculiarities. In this review we summarize the state of the art of research in this microorganisms, describing both pros and cons. We discuss (i) its halotolerance, (ii) the molecular factors involved in saline and osmotic stress, (iii) its high gene density and ambiguous CUG decoding, and (iv) its biotechnological and medical interests. We trust that all the bottlenecks in its study will soon be overcome and D. hansenii will become a fundamental organism for food biotechnological processes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27279568 TI - Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India. AB - BACKGROUND: The clinical phenotype of sickle cell disease (SCD) has been reported to be milder in India than in the United States. The objective of this large single-center study was to examine the rate of complications to define the phenotype of SCD in India. METHODS: The rate of complications per 100 person years in 833 pediatric SCD patients for 1954 person-years in Nagpur, India including those diagnosed on newborn screen (NBS) and those presenting later in childhood (non-NBS) was compared to those reported in the cooperative study of sickle cell disease (CSSCD). Event rates were also compared between patients belonging to scheduled castes (SCs), scheduled tribes (STs), and other backward classes (OBC). RESULTS: Comparison of CSSCD versus Nagpur NBS versus Nagpur non NBS for rates of pain (32.4 vs. 85.2 vs. 62.4), severe anemia (7.1 vs. 27 vs. 6.6), stroke (0.7 vs. 0.8 vs. 1.4), splenic sequestration (3.4 vs. 6.7 vs. 1.6), acute chest syndrome (24.5 vs. 23.6 vs. 1.0), and meningitis (0.8 vs. 0 vs. 0.1) revealed more frequent complications in Nagpur compared to CSSCD. Comparison of ST, SC, and OBC for rates of pain (84.6 vs. 71.9 vs. 63.5), acute chest syndrome (3.6 vs. 2.8 vs. 2.2), severe anemia (5.4 vs. 9.5 vs. 11.4), stroke (1.2 vs. 0.4 vs. 0.3), splenic sequestration (0.6 vs. 2.4 vs. 1.9), and meningitis (0.8 vs. 0 vs. 0.1) revealed significantly more frequent complications among ST. CONCLUSIONS: SCD-related complications are more frequent in Indian children than that observed in CSSCD. Further study is indicated to define SCD phenotype in India. PMID- 27279569 TI - Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis-induced acute renal injury. AB - Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti-inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 were measured with enzyme-linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor-kappaB signal pathway. PMID- 27279570 TI - Rifaximin, a non-absorbable antibiotic, inhibits the release of pro-angiogenic mediators in colon cancer cells through a pregnane X receptor-dependent pathway. AB - Activation of intestinal human pregnane X receptor (PXR) has recently been proposed as a promising strategy for the chemoprevention of inflammation-induced colon cancer. The present study was aimed at evaluating the effect of rifaximin, a non-absorbable antibiotic, in inhibiting angiogenesis in a model of human colorectal epithelium and investigating the role of PXR in its mechanism of action. Caco-2 cells were treated with rifaximin (0.1, 1.0 and 10.0 uM) in the presence or absence of ketoconazole (10 uM) and assessed for cell proliferation, migration and expression of proliferating cell nuclear antigen (PCNA). The release of vascular endothelial growth factor (VEGF) and nitric oxide (NO), expression of Akt, mechanistic target of rapamycin (mTOR), p38 mitogen activated protein kinases (MAPK), nuclear factor kappaB (NF-kappaB) and metalloproteinase-2 and -9 (MMP-2 and -9) were also evaluated. Treatment with rifaximin 0.1, 1.0 and 10.0 uM caused significant and concentration-dependent reduction of cell proliferation, cell migration and PCNA expression in the Caco-2 cells vs. untreated cells. Treatment downregulated VEGF secretion, NO release, VEGFR-2 expression, MMP-2 and MMP-9 expression vs. untreated cells. Rifaximin treatment also resulted in a concentration-dependent decrease in the phosphorylation of Akt, mTOR, p38MAPK and inhibition of hypoxia-inducible factor 1-alpha (HIF 1alpha), p70S6K and NF-kappaB. Ketoconazole (PXR antagonist) treatment inhibited these effects. These findings demonstrated that rifaximin causes PXR-mediated inhibition of angiogenic factors in Caco-2 cell line and may be a promising anticancer tool. PMID- 27279571 TI - Week 96 efficacy and safety of darunavir/ritonavir monotherapy vs. darunavir/ritonavir with two nucleoside reverse transcriptase inhibitors in the PROTEA trial. AB - OBJECTIVES: PROTEA is a randomized controlled trial to assess the efficacy and safety of darunavir/ritonavir (DRV/r) monotherapy as an alternative to triple therapy. METHODS: Patients fully suppressed on first-line antiretrovirals (viral load < 50 HIV-1 RNA copies/mL) were switched to DRV/r 800/100 mg once daily, either as monotherapy (n = 137) or with two nucleoside reverse transcriptase inhibitors (NRTIs) (n = 136). Treatment failure was HIV-1 RNA level >= 50 copies/mL at week 96 or discontinuation of study treatment [Food and Drug Administration (FDA) snapshot algorithm]. RESULTS: Patients were mainly male and white, with mean age 44 years. In the primary efficacy analysis, the percentage of patients with HIV-1 RNA < 50 copies/mL by week 96 [intent to treat (ITT)] was lower in the DRV/r monotherapy arm (103 of 137 patients; 75%) than in the triple therapy arm (116 of 136 patients; 85%) [difference -10.1%; 95% confidence interval (CI) -19.5, -0.7%]. In the switch-included analysis, monotherapy was noninferior to triple therapy. In a post hoc analysis, for patients with nadir CD4 count >= 200 cells/MUL, rates of HIV-1 RNA suppression were 82 of 96 patients (85%) in the DRV/r monotherapy arm and 88 of 106 patients (83%) in the triple therapy arm. No treatment-emergent primary protease inhibitor mutations were detected in either arm. The frequency of adverse events was similar in the two arms; however, one patient in the monotherapy arm was hospitalized with HIV encephalitis and elevated cerebrospinal fluid HIV-1 RNA. CONCLUSIONS: In this study, in patients with HIV-1 RNA < 50 copies/mL at baseline, switching to DRV/r monotherapy showed lower efficacy vs. triple therapy at week 96 in the primary ITT switch-equals-failure analysis, particularly in patients with CD4 counts < 200 cells/MUL. PMID- 27279572 TI - Nanoparticles-cell association predicted by protein corona fingerprints. AB - In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (O~ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells. PMID- 27279573 TI - L-homoarginine administration reduces neointimal hyperplasia in balloon-injured rat carotids. PMID- 27279574 TI - Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases. AB - PURPOSE: The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans. METHODS: Mice underwent MRI twice weekly for up to 31 d following intracardiac injection of the brain-homing breast cancer cell line MDA-MB231-BR. Patients with small cell lung cancer underwent quarterly MRI for 1 year. MTR and ADC were measured in regions of metastasis and matched contralateral tissue at the final time point and in registered regions at earlier time points. Texture analysis and linear discriminant analysis were performed to detect metastasis-containing slices. RESULTS: Compared with contralateral tissue, mouse metastases had significantly lower MTR and higher ADC at the final time point. Some lesions were visible at earlier time points on the MTR and ADC maps: 24% of these were not visible on corresponding T2 -weighted images. Texture analysis using the MTR maps showed 100% specificity and 98% sensitivity for metastasis at the final time point, with 77% sensitivity 2-4 d earlier and 46% 5 8 d earlier. Only 2 of 16 patients developed metastases, and their penultimate scans were normal. CONCLUSIONS: Some brain metastases may be detected earlier on MTR than conventional T2 ; however, the small gain is unlikely to justify "predictive" MRI. Magn Reson Med 77:1987-1995, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID- 27279575 TI - A novel Brassica-rhizotron system to unravel the dynamic changes in root system architecture of oilseed rape under phosphorus deficiency. AB - BACKGROUND AND AIMS: An important adaptation of plants to phosphorus (P) deficiency is to alter root system architecture (RSA) to increase P acquisition from the soil, but soil-based observations of RSA are technically challenging, especially in mature plants. The aim of this study was to investigate the root development and RSA of oilseed rape (Brassica napus L.) under low and high soil P conditions during an entire growth cycle. METHODS: A new large Brassica-rhizotron system (approx. 118-litre volume) was developed to study the RSA dynamics of B. napus 'Zhongshuang11' in soils, using top-soils supplemented with low P (LP) or high P (HP) for a full plant growth period. Total root length (TRL), root tip number (RTN), root length density (RLD), biomass and seed yield traits were measured. KEY RESULTS: TRL and RTN increased more rapidly in HP than LP plants from seedling to flowering stages. Both traits declined from flowering to silique stages, and then increased slightly in HP plants; in contrast, root senescence was observed in LP plants. RSA parameters measured from the polycarbonate plates were empirically consistent with analyses of excavated roots. Seed yield and shoot dry weights were closely associated positively with root dry weights, TRL, RLD and RTN at both HP and LP. CONCLUSIONS: The Brassica-rhizotron system is an effective method for soil-based root phenotyping across an entire growth cycle. Given that root senescence is likely to occur earlier under low P conditions, crop P deficiency is likely to affect late water and nitrogen uptake, which is critical for efficient resource use and optimal crop yields. PMID- 27279577 TI - A Comparison of Cost and Reward Procedures With Interdependent Group Contingencies. AB - The present study evaluated the effectiveness of two variations of a token economy for reducing disruptive behavior within a general education classroom. One variation involved a group contingency in which tokens were removed contingent on disruptive behavior (response cost), and the other variation involved a group contingency in which tokens were gained according to a differential reinforcement of other behavior schedule. Two elementary school teachers and their students participated. Results indicated that both procedures were effective in reducing the overall number of students disrupting; however, both teachers and students indicated a greater preference for the response cost condition. Implications for the use of these behavior management strategies in the classroom are discussed in terms of effectiveness and ease of implementation. PMID- 27279576 TI - Simulation of carbon allocation and organ growth variability in apple tree by connecting architectural and source-sink models. AB - BACKGROUND AND AIMS: Plant growth depends on carbon availability and allocation among organs. QualiTree has been designed to simulate carbon allocation and partitioning in the peach tree (Prunus persica), whereas MappleT is dedicated to the simulation of apple tree (Malus * domestica) architecture. The objective of this study was to couple both models and adapt QualiTree to apple trees to simulate organ growth traits and their within-tree variability. METHODS: MappleT was used to generate architectures corresponding to the 'Fuji' cultivar, accounting for the variability within and among individuals. These architectures were input into QualiTree to simulate shoot and fruit growth during a growth cycle. We modified QualiTree to account for the observed shoot polymorphism in apple trees, i.e. different classes (long, medium and short) that were characterized by different growth function parameters. Model outputs were compared with observed 3D tree geometries, considering shoot and final fruit size and growth dynamics. KEY RESULTS: The modelling approach connecting MappleT and QualiTree was appropriate to the simulation of growth and architectural characteristics at the tree scale (plant leaf area, shoot number and types, fruit weight at harvest). At the shoot scale, mean fruit weight and its variability within trees was accurately simulated, whereas the model tended to overestimate individual shoot leaf area and underestimate its variability for each shoot type. Varying the parameter related to the intensity of carbon exchange between shoots revealed that behaviour intermediate between shoot autonomy and a common assimilate pool was required to properly simulate within-tree fruit growth variability. Moreover, the model correctly dealt with the crop load effect on organ growth. CONCLUSIONS: This study provides understanding of the integration of shoot ontogenetic properties, carbon supply and transport between entities for simulating organ growth in trees. Further improvements regarding the integration of retroaction loops between carbon allocation and the resulting plant architecture are expected to allow multi-year simulations. PMID- 27279578 TI - Chronic Mastitis in Egypt and Morocco: Differentiating between Idiopathic Granulomatous Mastitis and IgG4-Related Disease. AB - Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases. PMID- 27279580 TI - Therapeutic Potential of the Medicinal Plant Aegle Marmelos (Linn.) Correa: Insight. AB - Various plant species are used globally for therapeutic purposes and have been authenticated by the World Health Organization. Aegle marmelos (L.) Corr., one of only three species in the genus Aegle, is a subtropical, fruit-bearing, deciduous tree that grows throughout the hills and plains of sub-Himalayan countries. Plants with medicinal importance have been used in almost every culture since ancient times. Various studies are underway to understand more about the qualities and components of medicinal plants, including drug preparation, phytochemical analysis, cultivation, toxicology, and pharmacology. According to the Indian conventional system of medicine, A. marmelos can successfully treat many diseases and conditions; for example, its extracts have been found to reduce the intensities of hepatic lipid peroxidation and augment the levels of hepatic antioxidants such as catalase, superoxide dismutase, and glutathione. The essential oils present in the foliage (leaves), fruits, and bark of A. marmelos provide strong antifungal action. A. marmelos is thus cytoprotective, works against ulcers and diarhea, promotes skin and bone healing, and acts as a hypoglycemic, antidiabetic, hepatoprotective, antimicrobial, analgesic, antiinflammatory, antipyretic, and anticancer agent. Such qualities have been well documented with scientific evidence. PMID- 27279579 TI - Regulation of tumorigenesis in oral epithelial cells by defined reprogramming factors Oct4 and Sox2. AB - Oct4 and Sox2 are pluripotent stem cell factors but the interplay between them in tumorigenesis is unclear. The aim of the present study was to investigate the roles of Oct4 and Sox2 in the reprogramming of oral cancer stem cells. One or both Oct4 and Sox2 were overexpressed in immortalized oral epithelial (hTERT+ OME) cells by lentivirus transduction. In addition, Oct4 and Sox2 proteins in two oral squamous cell carcinoma cell (OSCC) lines (Cal27 and primary cultured OSCC from a T2N2M0 patient) were individually or combinedly knocked down by shRNA. The results showed that the doubly transduced (Oct4+Sox2+) cells could trigger neoplasms in immunodeficient mice after lentivirus transduction, but single transduced (Oct4+ or Sox2+) cells had no tumor formation ability. The knockdown Sox2low and knockdown Oct4lowSox2low cells resulted in decreased tumor size in the immunodeficient mice but the single knockdown Oct4low cancer cells acquired more aggressive xenografts. Our findings suggest that Oct4+Sox2+ cells may be reprogrammed cancer stem cells inducing oral carcinogenesis. PMID- 27279581 TI - Photoprotective Effect of Carpomitra costata Extract against Ultraviolet B Induced Oxidative Damage in Human Keratinocytes. AB - Natural marine products show various biological properties such as antiphotoaging, antioxidant, anticancer, and anti-inflammation. This study evaluated the protective effects of the brown alga Carpomitra costata (Stackhouse) Batters (Sporochnaceae) against ultraviolet B (UVB)-provoked damage in human HaCaT keratinocytes. C. costata extract (CCE) effectively reduced superoxide anion, hydroxyl radical, and UVB-stimulated intracellular reactive oxygen species (ROS) levels. CCE also restored the expression and activity of UVB suppressed antioxidant enzymes. Furthermore, CCE decreased UVB-triggered oxidative damage to cellular components including DNA, protein, and lipid and defended the cells against mitochondrial membrane depolarization-medicated apoptosis. The results of this study indicate that CCE can safeguard human keratinocytes against UVB-induced cellular damage via a potent antioxidant mechanism. CCE may find utility as part of a therapeutic arsenal against the damaging effects of UVB radiation on the skin. PMID- 27279582 TI - Hepatoprotective and Immunosuppressive Effect of Synedrella nodiflora L. on Carbon Tetrachloride (CCl4)-Intoxicated Rats. AB - Synedrella nodiflora is a medicinal plant that is used by the natives of Sabah, Malaysia to treat rheumatism and several other ailments. This study aims to evaluate the ability of the crude aqueous extract of S. nodiflora leaves to protect against carbon tetrachloride (CCl4)-mediated hepatic injury in rats. S. nodiflora aqueous extract was orally administered to adult Sprague Dawley rats once daily for 14 days (150 and 300 mg/kg body weight [b.w.]) before CCl4 oral treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), hepatic antioxidant enzymes, and malondialdehyde (MDA) levels were estimated. Immunohistochemistry was performed for oxidative stress markers (4-hydroxynonenal [HNE], 8-hydroxy-deoxyguanosine [8-OHdG]) and proinflammatory markers (tumor necrosis factor-alpha, interleukin-6, prostaglandin E2). Biochemical, immunohistochemical, histological, and ultrastructural findings were in agreement to support the hepatoprotective effect of S. nodiflora against CCl4-mediated oxidative hepatic damage. Hepatoprotective effects of S. nodiflora might be attributable to the presence of phenolic antioxidants and their free radical scavenging property. PMID- 27279583 TI - Epithelial-Mesenchymal Transition: A Special Focus on Phthalates and Bisphenol A. AB - Epithelial-mesenchymal transition (EMT) is a process during which epithelial cells lose their polarity and ability to adhere. Instead, they gain properties to move, migrate through the extracellular matrix, become invasive, and finally become mesenchymal stem cells. This trans-differentiation is critical for embryo development, wound healing, and stem cell behavior. However, this same phenomenon is also observed in cancer progression. Phthalates and bisphenol A (BPA) are endocrine-disrupting chemicals (EDCs) that are linked to complex human diseases. These chemicals are suggested to disrupt normal hormonal balance (usually by existing estrogenic/antiandrogenic properties) and stimulate the development of reproductive tumors and steroid hormone-dependent cancers, such as breast cancer. Di(2-ethylhexyl) phthalate (DEHP), the most abundant phthalate, was shown to induce DNA damage in human cells via multiple molecular signals that include altered apoptosis and mitotic rate, increased cell proliferation, tumor mobility, and invasiveness of tumor cells. DEHP was also shown to inhibit gap junction intercellular communication and tight junctions and promote EMT. Phthalates may also cause the proliferation and metastasis of cancer cells and tumor progression via up-regulating histone deacetylase 6 (HDAC6). Phthalates can activate peroxisome proliferator activated receptors (PPARs) that may eventually lead to high proliferation of cancer cells. However, in ovarian cells the expression of Snail, Slug, and vimentin was enhanced by the treatment of BPA, whereas E cadherin was decreased. Mechanistic studies are needed to show the underlying mechanisms of EMT caused by different EDCs. PMID- 27279584 TI - Therapeutic Efficacy of Nigella Sativa Linn. against Antituberculosis Drug Induced Hepatic Injury in Wistar Rats. AB - Antituberculosis drug (ATD)-induced hepatotoxicity is a major impediment for the effective treatment of tuberculosis (TB). All first-line anti-TB medications have adverse effects that interrupt the successful completion of TB treatment. This investigation focuses on the evaluation of the protective role of Nigella sativa (NS) against liver injury caused by ATDs. Female rats were treated with ATDs for 8 weeks (3 d/wk) followed by NS for 8 weeks (3 d/wk). The antioxidant activity of NS was estimated with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and by analyzing total phenolic contents. Qualitative characterization of active compounds of the plant was done by high-performance liquid chromotography (HPLC). ATD-induced adverse effects were associated with sharp elevation in levels of serum transaminases, albumin, cholesterol, urea, uric acid, creatinine, and blood urea nitrogen (BUN). ATDs significantly increased lipid peroxidation (LPO) and decreased enzyme activities (superoxide dismutase [SOD], catalase [CAT], adenosine triphosphatase [ATPase], and glucose-6-phosphatase [G6Pase]) in liver, indicating oxidative stress. Conjoint treatment with NS could reverse the serological biochemistry and inhibit oxidative stress by suppressing LPO and augmenting antioxidant enzyme activity toward that of the control. Histological studies support the above biochemical findings. Results indicate that NS exerts excellent hepatoprotective abilities and can be used as a supplement to improve patient adherence and reduce interruptions in treatment due to ATD-related liver injury. PMID- 27279585 TI - Resveratrol Alleviates Cadmium-Induced Damage and Overexpression of Epidermal Growth Factor Receptor and its Downstream Signaling Proteins in the Reproductive System of Male Swiss Albino Mice. AB - Nowadays, exposure to heavy metals and their detrimental effects in humans are grave health concerns. In this study, we investigated the protective effect of resveratrol (RES) against CdCl2 (cadmium chloride)-induced impairment of spermatogenesis, histopathological alterations, and the up-regulation of epidermal growth factor receptor (EGFR) signaling cascade in Swiss albino mice. Two different doses of CdCl2 were injected intraperitoneally into two groups of mice, and in the third group RES was administered orally before injecting CdCl2 (3 times/wk) for 14 days. Sperm motility, count, vitality, and morphology were analyzed. Hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC), and western blot analyses were performed on testis tissue. In CdCl2-administered animals, significant perturbations of spermatogenesis and histoarchitecture of seminiferous tubules were observed. p-EGFR, p-AKT, AKT1/2/3, NF-kappabeta (p50), and COX-2 of the EGFR cascade were up-regulated. Although there was significant negative correlation between percentage of motile cells and protein expression, we found positive correlation between morphologically abnormal cells and overexpression of proteins in CdCl2-only treated groups. Marked improvement of sperm parameters and histopathological damages as well as down-regulation of the EGFR signaling cascade were observed in the RES-pretreated mice. Hence, the present study elucidates that RES protects against CdCl2-induced perturbation of spermatogenesis and overexpression of EGFR and its downstream signaling proteins. PMID- 27279586 TI - Comparing the Effects of Light- or Sonic-Activated Drug Delivery: Photochemical/Sonochemical Internalization. AB - Photochemical internalization (PCI) is a technique that uses the photochemical properties of photodynamic therapy (PDT) for the enhanced delivery of endolysosomal-trapped macromolecules into the cell cytoplasm. The released agent can therefore exert its full biological activity, in contrast to being degraded by lysosomal hydrolases. Activation of photosensitizers via ultrasound (US), called sonodynamic therapy (SDT), has been proposed as an alternative to light activated PDT for the treatment of cancerous tumors. The use of focused US (FUS) to activate photosensitizers allows treatment at tumor sites buried deep within tissues, overcoming one of the main limitations of PDT/PCI. We have examined ultrasonic activation of photosensitizers together with the anticancer agent bleomycin (BLM) using sonochemical internalization (SCI), as an alternative to light-activated PCI. Our results indicate that, compared to drug or US treatment alone, US activation of the photosensitizer AlPcS2a together with BLM significantly inhibits the ability of treated glioma cells to form clonogenic colonies. PMID- 27279588 TI - Multiple sclerosis should be treated using a step-down strategy rather than a step-up strategy-YES. PMID- 27279587 TI - Radiation-Induced Differentiated Thyroid Cancer Is Associated with Improved Overall Survival but Not Thyroid Cancer-Specific Mortality or Disease-Free Survival. AB - BACKGROUND: Radiation is a well-described risk factor for differentiated thyroid carcinoma (DTC). Although the natural history of DTC following nuclear disasters and in healthcare workers with chronic radiation exposure (RE) has been described, little is known about DTC following short-term exposure to therapeutic medical radiation for benign disease. This study compares DTC morphology and outcomes in patients with and without a prior history of therapeutic external RE. METHODS: A retrospective review was performed of patients with DTC treated at The University of Chicago between 1951 and 1987, with a median follow-up of 27 years (range 0.3-60 years). Patients were classified as either having (RE+) or not having (RE-) a history of therapeutic RE. Variables examined included sex, age at RE, dose of RE, indication for RE, DTC histology, and outcome. Morphology was determined by blinded retrospective review of all available histologic slides. Outcomes were assessed using Cox proportional hazards model and Kaplan-Meier curves. RESULTS: Of 257 DTC patients, 165 (64%) were RE- and 92 (36%) were RE+, with males comprising a greater proportion of the RE+ group (43.5% vs. 27.3%; p = 0.01). A total of 94.2% of DTC cases were classic papillary cancers; histology did not differ between RE+ and RE- cohorts (p = 0.73). RE was associated with an increased median overall survival (OS; 43 years vs. 38 years; hazard ratio [HR] = 0.55 [confidence interval (CI) 0.34-0.89]; p = 0.01). Survival for males in the RE- group was significantly worse than it was for RE- females (HR = 1.78 [CI 1.05 3.03]; p = 0.03) or RE+ males (HR = 2.98 [CI 1.39-6.38]; p = 0.01). Recurrence did not differ between the RE+ and RE- groups (HR = 0.85 [CI 0.52-1.41]; p = 0.54), nor did DTC-specific mortality (HR = 0.54 [CI 0.21-1.37]; p = 0.20). CONCLUSIONS: While DTC following RE has historically been considered a more aggressive variant than DTC in the absence of RE, the present data indicate that RE+ DTC is associated with better OS than RE- DTC, especially for males. Additionally, recent reports are confirmed of equivalent rates of thyroid cancer recurrence. These results warrant further investigation into the factors underlying this unexpected finding. PMID- 27279589 TI - Multiple sclerosis should be treated using a step-down strategy rather than a step-up strategy-Commentary. PMID- 27279590 TI - Multiple sclerosis should be treated using a step-down strategy rather than a step-up strategy-NO. PMID- 27279592 TI - Pigmentary incontinence in the skin of the planum nasale from normal dogs. PMID- 27279593 TI - Transcriptome activity of isochores during preimplantation process in human and mouse. AB - This work investigates the role of isochores during preimplantation process. Using RNA-seq data from human and mouse preimplantation stages, we created the spatio-temporal transcriptional profiles of the isochores during preimplantation. We found that from early to late stages, GC-rich isochores increase their expression while GC-poor ones decrease it. Network analysis revealed that modules with few coexpressed isochores are GC-poorer than medium-large ones, characterized by an opposite expression as preimplantation advances, decreasing and increasing respectively. Our results reveal a functional contribution of the isochores, supporting the presence of structural-functional interactions during maturation and early-embryonic development. PMID- 27279591 TI - Preoperative intra-aortic balloon pump improves the clinical outcomes of off-pump coronary artery bypass grafting in left ventricular dysfunction patients. AB - Severe left ventricular (LV) dysfunction patients undergoing off-pump coronary artery bypass grafting (OPCAB) are often associated with a higher mortality. The efficacy and safety of the preoperative prophylactic intra-aortic balloon pump (IABP) insertion is not well established. 416 consecutive patients with severe LV dysfunction (ejection fraction <=35%) undergoing isolated OPCAB were enrolled in a retrospective observational study. 191 patients was enrolled in the IABP group; the remaining 225 patients was in control group. A total of 129 pairs of patients were propensity-score matched. No significant differences in demographic and preoperative risk factors were found between the two groups. The postoperative 30 day mortality occurred more frequently in the control group compared with the IABP group (8.5% vs. 1.6%, p = 0.02). There was a significant reduction of low cardiac output syndrome in the IABP group compared with the control group (14% vs. 6.2%, p = 0.04). Prolonged mechanical ventilation (>=48 h) occurred more frequently in the control group (34.9% vs. 20.9%, p = 0.02). IABP also decreased the postoperative length of stay. Preoperative IABP was associated with a lower 30-day mortality, suggesting that it is effective in patients with severe LV dysfunction undergoing OPCAB. PMID- 27279594 TI - Tracking airborne CO2 mitigation and low cost transformation into valuable carbon nanotubes. AB - Primary evidence of the direct uptake of atmospheric CO2 and direct transformation into carbon nanotubes, CNTs, is demonstrated through isotopic labeling, and provides a new high yield route to mitigate this greenhouse gas. CO2 is converted directly to CNTs and does not require pre-concentration of the airbone CO2. This C2CNT (CO2 to carbon nanotube) synthesis transforms CO2-gas dissolved in a 750 degrees C molten Li2CO3, by electrolysis, into O2-gas at a nickel electrode, and at a steel cathode into CNTs or carbon or nanofibers, CNFs. CNTs are synthesized at a 100-fold price reduction compared to conventional chemical vapour deposition, CVD, synthesis. The low cost conversion to a stable, value-added commodity incentivizes CO2 removal to mitigate climate change. The synthesis allows morphology control at the liquid/solid interface that is not available through conventional CVD synthesis at the gas/solid interface. Natural abundance (12)CO2 forms hollow CNTs, while equivalent synthetic conditions with heavier (13)CO2 favours closed core CNFs, as characterized by Raman, SEM and TEM. Production ease is demonstrated by the first synthesis of a pure (13)C multiwalled carbon nanofiber. PMID- 27279595 TI - Risk-Mitigating Policies and Adversarial Behavior: Case of Backlash. AB - A probabilistic game-theoretic model is developed within both a static and a dynamic framework to capture adversary-defender conflict in the presence of backlash. I find that not accounting for backlash in counteradversary policies may be costly to the target government. But to minimize adversarial backlash requires understanding how backlash emerges and if, and how, adversaries strategize to goad target governments into policies that induce backlash. The dynamic version of the model shows that when backlash occurs with a time lag, an escalation of the conflict is likely to occur. PMID- 27279596 TI - Evaluating a Research Training Programme for People with Intellectual Disabilities Participating in Inclusive Research: The Views of Participants. AB - BACKGROUND: This article presents the results of evaluating a research training programme aimed at developing the skills of people with intellectual disabilities to actively participate in inclusive research. METHODS: The present authors opted for a responsive approach to evaluation, using a combination of interviews, questionnaires and focus groups to gather information on the views of students, trainers and members of the research team regarding how the programme progressed, the learning achieved and participants' satisfaction with the programme. RESULTS: The evaluation showed that most of the participants were satisfied with the programme and provided guidelines for planning contents and materials, demonstrating the usefulness of these types of programme in constructing the research group and empowering people with intellectual disabilities to participate in research. CONCLUSIONS: The evaluation revealed that the programme had been a positive social experience that fostered interest in lifelong learning for people with intellectual disabilities. PMID- 27279598 TI - Astragalus polysaccharide induces the apoptosis of human hepatocellular carcinoma cells by decreasing the expression of Notch1. AB - Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death worldwide. Astragalus polysaccharide (APS), the primary active component extracted from a traditional Chinese medicinal herb Astragalus membranaceus, has been proved to exert a marked inhibitory effect on a number of types of human solid tumors. In the present study, we aimed to examine the effects of APS on the survival of the HCC cell line H22 and to elucidate the underlying regulatory mechanisms responsible for these effects. Our results revealed that the mRNA and protein expression of Notch1 was significantly upregulated in the HCC tissues compared with that in the normal tissues. APS decreased cell viability and induced the apoptosis of HCC cells in a concentration-dependent manner, which were evaluated using a cell counting kit-8 (CCK-8) assay and flow cytometric analysis, respectively. Furthermore, APS regulated the expression of apoptosis related genes (Bcl-2 and BAX) and proteases (caspase-3 and -8). Mechanically, Notch1 expression was found to be suppressed in HCC cells, and further analysis indicated that Notch1 knockdown by siRNA significantly reduced cell viability, suppressed the metastatic capacity and enhanced the apoptosis of HCC cells. Taken together, these findings suggest that Notch1 may be a potential therapeutic target for the treatment of HCC. PMID- 27279597 TI - Performance of trigger tools in identifying adverse drug events in emergency department patients: a validation study. AB - AIMS: Trigger tools are retrospective surveillance methods that can be used to identify adverse drug events (ADEs), unintended and harmful effects of medications, in medical records. Trigger tools are used in quality improvement, public health surveillance and research activities. The objective of the study was to evaluate the performance of trigger tools in identifying ADEs. METHODS: This study was a sub-study of a prospective cohort study which enrolled adults presenting to one tertiary care emergency department. Clinical pharmacists evaluated patients for ADEs at the point-of-care. Twelve months after the prospective study's completion, the patients' medical records were reviewed using eight different trigger tools. ADEs identified using each trigger tool were compared with events identified at the point-of-care. The primary outcome was the sensitivity of each trigger tool for ADEs. RESULTS: Among 1151 patients, 152 (13.2%, 95% confidence intervals (CI) 11.4, 15.3%) were diagnosed with one or more ADEs at the point-of-care. The sensitivity of the trigger tools for detecting ADEs ranged from 2.6% (95% CI 0.7, 6.6%) to 15.8% (95% CI 10.6, 22.8%). Their specificity varied from 99.3% (95% CI 98.6, 99.7) to 100% (95% CI 99.6, 100%). CONCLUSION: The trigger tools examined had poor sensitivity for identifying ADEs in emergency department patients, when applied manually and in retrospect. Reliance on these methods to detect ADEs for quality improvement, surveillance, and research activities is likely to underestimate their occurrence, and may lead to biased estimates. PMID- 27279599 TI - Simultaneous extraction and preconcentration of aniline, phenol, and naphthalene using magnetite-graphene oxide composites before gas chromatography determination. AB - The coextraction of acidic and basic compounds from different mediums is a significant concept in sample preparation. In this work, simultaneous extraction of acidic, basic, and neutral analytes in a single step was carried out for the first time. This procedure employed the dispersive solid-phase microextraction of analytes with magnetic graphene oxide (graphene oxide/Fe3 O4 ) sorbent followed by gas chromatography with flame ionization detection. After the adsorption of analytes by vortexing and decantation of the supernatant with a magnet, the sorbent was eluted with acetonitrile/methanol (2:1) mixture. The parameters affecting the extraction efficiency were optimized and obtained as follows: sorbent amount 60 mg, desorption time 1 min, extraction time 5 min, pH of the sample 7, sample volume 20 mL, and elution solvent volume 0.3 mL. Under the optimum conditions, linear dynamic ranges were achieved in the range of 0.5-4, 0.25-4, and 0.25-2 MUg/mL and limits of detection were 0.341, 0.110, and 0.167 MUg/mL for aniline, phenol, and naphthalene, respectively. The relative standard deviations were in the range of 3.3-5.7% in eight repeated extractions. Finally, the applicability of the method was evaluated by the extraction and determination of analytes in stream water and drinking water samples and satisfactory results were obtained. PMID- 27279600 TI - Incidental Finding and Management of Mesenteric Fibromatosis. AB - BACKGROUND: Mesenteric fibromatosis, also known as mesenteric desmoids, is part of the clinical-pathologic spectrum of deep fibromatosis, which encompasses a group of benign fibro-proliferative processes that are locally aggressive and have the capacity to infiltrate or recur without metastasis. CASE REPORT: Case of a 45-year-old man, with a history of hypertension and lung fibrosis, presenting for a left abdominal mass, which was found incidentally during his lung fibrosis imaging. He complained of constipation due to pressure upon his bowel leading to difficulty in defecation. CONCLUSIONS: Although there are many overlapping criteria between gastrointestinal stromal tumors and mesenteric fibromatosis, making it difficult to discriminate between the two, there are differences that are unique to mesenteric fibromatosis that should be noticed during the diagnosis. In this case, mesenteric fibromatosis was unusual as it is not associated with Gardner's syndrome, desmoid tumors, nor familial adenomatous polyposis, but was an incidental finding. PMID- 27279601 TI - Browning of White Fat: Novel Insight Into Factors, Mechanisms, and Therapeutics. AB - What is more interesting about brown adipose tissue (BAT) is its ability to provide thermogenesis, protection against obesity by clearing triglycerides, releasing batokines, and mitigating insulin resistance. White adipose tissue (WAT) on the other hand stores excess energy and secretes some endocrine factors like leptin for regulating satiety. For the last decade there has been an increasing interest in the browning of fat keeping in view its beneficial effects on metabolic disorders and protection in the form of perivascular fat. Obesity is one such metabolic disorder that leads to significant morbidity and mortality from obesity-related disorders such as type 2 diabetes mellitus (T2D) and cardiovascular disease risk. Browning of white fat paves the way to restrict obesity and obesity related disorders. Although exercise has been the most common factor for fat browning; however, there are other factors that involve: (1) beta aminoisobutyric acid (BAIBA); (2) gamma amino butyric acid (GABA); (3) PPARgamma agonists; (4) JAK inhibition; and (5) IRISIN. In this review, we propose two novel factors musclin and TFAM for fat browning. Musclin a myokine released from muscles during exercise activates PPARgamma which induces browning of WAT that has beneficial metabolic and cardiac effects. TFAM is a transcription factor that induces mitochondrial biogenesis. Since BAT is rich in mitochondria, higher expression of TFAM in WAT or TFAM treatment in WAT cells can induce browning of WAT. We propose that fat browning can be used as a therapeutic tool for metabolic disorders and cardiovascular diseases. J. Cell. Physiol. 232: 61-68, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 27279602 TI - Naltrexone at low doses upregulates a unique gene expression not seen with normal doses: Implications for its use in cancer therapy. AB - It has been reported that lower doses of the opioid antagonist naltrexone are able to reduce tumour growth by interfering with cell signalling as well as by modifying the immune system. We have evaluated the gene expression profile of a cancer cell line after treatment with low-dose naltrexone (LDN), and assessed the effect that adapting treatment schedules with LDN may have on enhancing efficacy. LDN had a selective impact on genes involved with cell cycle regulation and immune modulation. Similarly, the pro-apoptotic genes BAD and BIK1 were increased only after LDN. Continuous treatment with LDN had little effect on growth in different cell lines; however, altering the treatment schedule to include a phase of culture in the absence of drug following an initial round of LDN treatment, resulted in enhanced cell killing. Furthermore, cells pre-treated with LDN were more sensitive to the cytotoxic effects of a number of common chemotherapy agents. For example, priming HCT116 with LDN before treatment with oxaliplatin significantly increased cell killing to 49+/-7.0 vs. 14+/-2.4% in cultures where priming was not used. Interestingly, priming with NTX before oxaliplatin resulted in just 32+/-1.8% cell killing. Our data support further the idea that LDN possesses anticancer activity, which can be improved by modifying the treatment schedule. PMID- 27279603 TI - Is There a Role for Genetics in the Prevention of Sudden Cardiac Death? AB - The identification of patients at risk for sudden cardiac death (SCD) is fundamental for both acquired cardiovascular diseases (such as coronary artery diseases, CAD) and inherited arrhythmia syndromes (such as the long-QT syndrome, LQTS). Genetics may play a role in both situations, although the potential to exploit this information to reduce the burden of SCD varies among these two groups. Concerning acquired cardiovascular diseases, which affect most of the general population, preliminary data suggest an association between genetics and the risk of dying suddenly. The maximal utility, instead, is reached in inherited arrhythmia syndromes, where the discovery of monogenic diseases such as LQTS tracked the way for the first genotype-phenotype correlations. The aim of this review is to provide a general overview focusing on the current genetic knowledge and on the present and future applicability for prevention in these two populations at risk for SCD. PMID- 27279604 TI - Effectiveness of medical self-experience counseling in pregnant women after echocardiographic detection of a suspected fetal heart anomaly: A longitudinal study. AB - AIM: The purpose of this longitudinal study was to assess maternal psychological responses after echocardiographic detection of a suspected fetal heart anomaly and to evaluate a medical self-experience counseling intervention in improving psychological responses. METHODS: A total of 751 women were referred to Shandong Provincial Hospital, Jinan during May 2014 and April 2015. To analyze the psychological impact on the mothers, the groups were divided into mild, intermediate and severe, according to heart defect severity. State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II) questionnaires were distributed in three steps: first evaluation, after the diagnostic examination; second evaluation, two weeks after step one, both study and control groups underwent routine psychological counseling; third evaluation, two weeks after step two, study groups underwent self-experience counseling and controls underwent routine counseling. Anxiety and depression scores and above clinical cut-off percentages in the subgroups were calculated and compared. RESULTS: The severity of anxiety and depression was not significantly relieved with the alleviative type of suspicious heart abnormality. State-STAI and BDI-II scores and above clinical cut-off percentages were statistically different between steps 2 and 3 in intermediate and mild mothers. Women in control groups did not exhibit obvious relief of anxiety and depression. CONCLUSION: Women pregnant with fetuses with mild or intermediate fetal heart abnormalities presented heightened levels of depression and anxiety when compared with mothers pregnant with fetuses with severe heart disease. Medical self-experience counseling played an important role in relieving anxiety and depression in these mothers. PMID- 27279605 TI - P3N-PIPO, a Frameshift Product from the P3 Gene, Pleiotropically Determines the Virulence of Clover Yellow Vein Virus in both Resistant and Susceptible Peas. AB - Peas carrying the cyv1 recessive resistance gene are resistant to clover yellow vein virus (ClYVV) isolates No.30 (Cl-No.30) and 90-1 (Cl-90-1) but can be infected by a derivative of Cl-90-1 (Cl-90-1 Br2). The main determinant for the breaking of cyv1 resistance by Cl-90-1 Br2 is P3N-PIPO produced from the P3 gene via transcriptional slippage, and the higher level of P3N-PIPO produced by Cl-90 1 Br2 than by Cl-No.30 contributes to the breaking of resistance. Here we show that P3N-PIPO is also a major virulence determinant in susceptible peas that possess another resistance gene, Cyn1, which does not inhibit systemic infection with ClYVV but causes hypersensitive reaction-like lethal systemic cell death. We previously assumed that the susceptible pea cultivar PI 226564 has a weak allele of Cyn1 Cl-No.30 did not induce cell death, but Cl-90-1 Br2 killed the plants. Our results suggest that P3N-PIPO is recognized by Cyn1 and induces cell death. Unexpectedly, heterologously strongly expressed P3N-PIPO of Cl-No.30 appears to be recognized by Cyn1 in PI 226564. The level of P3N-PIPO accumulation from the P3 gene of Cl-No.30 was significantly lower than that of Cl-90-1 Br2 in a Nicotiana benthamiana transient assay. Therefore, Cyn1-mediated cell death also appears to be determined by the level of P3N-PIPO. The more efficiently a ClYVV isolate broke cyv1 resistance, the more it induced cell death systemically (resulting in a loss of the environment for virus accumulation) in susceptible peas carrying Cyn1, suggesting that antagonistic pleiotropy of P3N-PIPO controls the resistance breaking of ClYVV. IMPORTANCE: Control of plant viral disease has relied on the use of resistant cultivars; however, emerging mutant viruses have broken many types of resistance. Recently, we revealed that Cl-90-1 Br2 breaks the recessive resistance conferred by cyv1, mainly by accumulating a higher level of P3N-PIPO than that of the nonbreaking isolate Cl-No.30. Here we show that a susceptible pea line recognized the increased amount of P3N-PIPO produced by Cl 90-1 Br2 and activated the salicylic acid-mediated defense pathway, inducing lethal systemic cell death. We found a gradation of virulence among ClYVV isolates in a cyv1-carrying pea line and two susceptible pea lines. This study suggests a trade-off between breaking of recessive resistance (cyv1) and host viability; the latter is presumably regulated by the dominant Cyn1 gene, which may impose evolutionary constraints upon P3N-PIPO for overcoming resistance. We propose a working model of the host strategy to sustain the durability of resistance and control fast-evolving viruses. PMID- 27279606 TI - Complex Interplay between HIV-1 Capsid and MX2-Independent Alpha Interferon Induced Antiviral Factors. AB - Type I interferons (IFNs), including IFN-alpha, upregulate an array of IFN stimulated genes (ISGs) and potently suppress Human immunodeficiency virus type 1 (HIV-1) infectivity in CD4(+) T cells, monocyte-derived macrophages, and dendritic cells. Recently, we and others identified ISG myxovirus resistance 2 (MX2) as an inhibitor of HIV-1 nuclear entry. However, additional antiviral blocks exist upstream of nuclear import, but the ISGs that suppress infection, e.g., prior to (or during) reverse transcription, remain to be defined. We show here that the HIV-1 CA mutations N74D and A105T, both of which allow escape from inhibition by MX2 and the truncated version of cleavage and polyadenylation specific factor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A, all increase sensitivity to IFN-alpha-mediated inhibition. Using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology, we demonstrate that the IFN-alpha hypersensitivity of these mutants in THP-1 cells is independent of MX2 or CPSF6. As expected, CypA depletion had no additional effect on the behavior of the P90A mutant but modestly increased the IFN-alpha sensitivity of wild-type virus. Interestingly, the infectivity of wild type or P90A virus could be rescued from the MX2-independent IFN-alpha-induced blocks in THP-1 cells by treatment with cyclosporine (Cs) or its nonimmunosuppressive analogue SDZ-NIM811, indicating that Cs-sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-alpha-induced blocks. We propose that cellular interactions with incoming HIV-1 capsids help shield the virus from recognition by antiviral effector mechanisms. Thus, the CA protein is a fulcrum for the dynamic interplay between cell-encoded functions that inhibit or promote HIV-1 infection. IMPORTANCE: HIV-1 is the causative agent of AIDS. During acute HIV-1 infection, numerous proinflammatory cytokines are produced, including type I interferons (IFNs). IFNs can limit HIV-1 replication by inducing the expression of a set of antiviral genes that inhibit HIV-1 at multiple steps in its life cycle, including the postentry steps of reverse transcription and nuclear import. This is observed in cultured cell systems, as well as in clinical trials in HIV-1-infected patients. The identities of the cellular antiviral factors, their viral targets, and the underpinning mechanisms are largely unknown. We show here that the HIV-1 Capsid protein plays a central role in protecting the virus from IFN-induced inhibitors that block early postentry steps of infection. We further show that host cell cyclophilins play an important role in regulating these processes, thus highlighting the complex interplay between antiviral effector mechanisms and viral survival. PMID- 27279607 TI - Role of Conserved E2 Residue W420 in Receptor Binding and Hepatitis C Virus Infection. AB - Hepatitis C virus (HCV) enters cells via interactions with several host factors, a key one being that between the viral E2 envelope glycoprotein and the CD81 receptor. We previously identified E2 tryptophan residue 420 (W420) as an essential CD81-binding residue. However, the importance of W420 in the context of the native virion is unknown, as those previous studies predate the infectious HCV cell culture (cell culture-derived HCV [HCVcc]) system. Here, we introduced four separate mutations (F, Y, A, or R) at position 420 within the infectious HCVcc JFH-1 genome and characterized their effects on the viral life cycle. While all mutations reduced E2-CD81 binding, only two (W420A and W420R) reduced HCVcc infectivity. Further analyses of mutants with hydrophobic residues (F or Y) found that interactions with the receptors SR-BI and CD81 were modulated, which in turn determined the viral uptake route. Both mutant viruses were significantly less dependent on SR-BI, and its lipid transfer activity, for virus entry. Furthermore, these viruses were resistant to the drug erlotinib, which targets epidermal growth factor receptor (EGFR) (a host cofactor for HCV entry) and also blocks SR-BI-dependent high-density lipoprotein (HDL)-mediated enhancement of virus entry. Together, our data indicate a model where an alteration at position 420 causes a subtle change in the E2 conformation that prevents interaction with SR-BI and increases accessibility to the CD81-binding site, in turn favoring a particular internalization route. These results further show that a hydrophobic residue with a strong preference for tryptophan at position 420 is important, both functionally and structurally, to provide an additional hydrophobic anchor to stabilize the E2-CD81 interaction. IMPORTANCE: Hepatitis C virus (HCV) is a leading cause of liver disease, causing up to 500,000 deaths annually. The first step in the viral life cycle is the entry process. This study investigates the role of a highly conserved residue, tryptophan residue 420, of the viral glycoprotein E2 in this process. We analyzed the effect of changing this residue in the virus and confirmed that this region is important for binding to the CD81 receptor. Furthermore, alteration of this residue modulated interactions with the SR-BI receptor, and changes to these key interactions were found to affect the virus internalization route involving the host cofactor EGFR. Our results also show that the nature of the amino acid at this position is important functionally and structurally to provide an anchor point to stabilize the E2-CD81 interaction. PMID- 27279608 TI - Homology-Based Identification of a Mutation in the Coronavirus RNA-Dependent RNA Polymerase That Confers Resistance to Multiple Mutagens. AB - Positive-sense RNA viruses encode RNA-dependent RNA polymerases (RdRps) essential for genomic replication. With the exception of the large nidoviruses, such as coronaviruses (CoVs), RNA viruses lack proofreading and thus are dependent on RdRps to control nucleotide selectivity and fidelity. CoVs encode a proofreading exonuclease in nonstructural protein 14 (nsp14-ExoN), which confers a greater than-10-fold increase in fidelity compared to other RNA viruses. It is unknown to what extent the CoV polymerase (nsp12-RdRp) participates in replication fidelity. We sought to determine whether homology modeling could identify putative determinants of nucleotide selectivity and fidelity in CoV RdRps. We modeled the CoV murine hepatitis virus (MHV) nsp12-RdRp structure and superimposed it on solved picornaviral RdRp structures. Fidelity-altering mutations previously identified in coxsackie virus B3 (CVB3) were mapped onto the nsp12-RdRp model structure and then engineered into the MHV genome with [nsp14-ExoN(+)] or without [nsp14-ExoN(-)] ExoN activity. Using this method, we identified two mutations conferring resistance to the mutagen 5-fluorouracil (5-FU): nsp12-M611F and nsp12 V553I. For nsp12-V553I, we also demonstrate resistance to the mutagen 5 azacytidine (5-AZC) and decreased accumulation of mutations. Resistance to 5-FU, and a decreased number of genomic mutations, was effectively masked by nsp14-ExoN proofreading activity. These results indicate that nsp12-RdRp likely functions in fidelity regulation and that, despite low sequence conservation, some determinants of RdRp nucleotide selectivity are conserved across RNA viruses. The results also indicate that, with regard to nucleotide selectivity, nsp14-ExoN is epistatic to nsp12-RdRp, consistent with its proposed role in a multiprotein replicase-proofreading complex. IMPORTANCE: RNA viruses have evolutionarily fine tuned replication fidelity to balance requirements for genetic stability and diversity. Responsibility for replication fidelity in RNA viruses has been attributed to the RNA-dependent RNA polymerases, with mutations in RdRps for multiple RNA viruses shown to alter fidelity and attenuate virus replication and virulence. Coronaviruses (CoVs) are the only known RNA viruses to encode a proofreading exonuclease (nsp14-ExoN), as well as other replicase proteins involved in regulation of fidelity. This report shows that the CoV RdRp (nsp12) likely functions in replication fidelity; that residue determinants of CoV RdRp nucleotide selectivity map to similar structural regions of other, unrelated RNA viral polymerases; and that for CoVs, the proofreading activity of the nsp14-ExoN is epistatic to the function of the RdRp in fidelity. PMID- 27279609 TI - Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes. AB - African horse sickness virus (AHSV), an orbivirus in the Reoviridae family with nine different serotypes, causes devastating disease in equids. The virion particle is composed of seven proteins organized in three concentric layers, an outer layer made of VP2 and VP5, a middle layer made of VP7, and inner layer made of VP3 that encloses a replicase complex of VP1, VP4, and VP6 and a genome of 10 double-stranded RNA segments. In this study, we sought to develop highly efficacious candidate vaccines against all AHSV serotypes, taking into account not only immunogenic and safety properties but also virus productivity and stability parameters, which are essential criteria for vaccine candidates. To achieve this goal, we first established a highly efficient reverse genetics (RG) system for AHSV serotype 1 (AHSV1) and, subsequently, a VP6-defective AHSV1 strain in combination with in trans complementation of VP6. This was then used to generate defective particles of all nine serotypes, which required the exchange of two to five RNA segments to achieve equivalent titers of particles. All reassortant-defective viruses could be amplified and propagated to high titers in cells complemented with VP6 but were totally incompetent in any other cells. Furthermore, these replication-incompetent AHSV particles were demonstrated to be highly protective against homologous virulent virus challenges in type I interferon receptor (IFNAR)-knockout mice. Thus, these defective viruses have the potential to be used for the development of safe and stable vaccine candidates. The RG system also provides a powerful tool for the study of the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis. IMPORTANCE: African horse sickness virus is transmitted by biting midges and causes African horse sickness in equids, with mortality reaching up to 95% in naive horses. Therefore, the development of efficient vaccines is extremely important due to major economic losses in the equine industry. Through the establishment of a highly efficient RG system, replication-deficient viruses of all nine AHSV serotypes were generated. These defective viruses achieved high titers in a cell line complemented with VP6 but failed to propagate in wild-type mammalian or insect cells. Importantly, these candidate vaccine strains showed strong protective efficacy against AHSV infection in an IFNAR(-/-) mouse model. PMID- 27279610 TI - Virion Structure of Iflavirus Slow Bee Paralysis Virus at 2.6-Angstrom Resolution. AB - The western honeybee (Apis mellifera) is the most important commercial insect pollinator. However, bees are under pressure from habitat loss, environmental stress, and pathogens, including viruses that can cause lethal epidemics. Slow bee paralysis virus (SBPV) belongs to the Iflaviridae family of nonenveloped single-stranded RNA viruses. Here we present the structure of the SBPV virion determined from two crystal forms to resolutions of 3.4 A and 2.6 A. The overall structure of the virion resembles that of picornaviruses, with the three major capsid proteins VP1 to 3 organized into a pseudo-T3 icosahedral capsid. However, the SBPV capsid protein VP3 contains a C-terminal globular domain that has not been observed in other viruses from the order Picornavirales The protruding (P) domains form "crowns" on the virion surface around each 5-fold axis in one of the crystal forms. However, the P domains are shifted 36 A toward the 3-fold axis in the other crystal form. Furthermore, the P domain contains the Ser-His-Asp triad within a surface patch of eight conserved residues that constitutes a putative catalytic or receptor-binding site. The movements of the domain might be required for efficient substrate cleavage or receptor binding during virus cell entry. In addition, capsid protein VP2 contains an RGD sequence that is exposed on the virion surface, indicating that integrins might be cellular receptors of SBPV. IMPORTANCE: Pollination by honeybees is needed to sustain agricultural productivity as well as the biodiversity of wild flora. However, honeybee populations in Europe and North America have been declining since the 1950s. Honeybee viruses from the Iflaviridae family are among the major causes of honeybee colony mortality. We determined the virion structure of an Iflavirus, slow bee paralysis virus (SBPV). SBPV exhibits unique structural features not observed in other picorna-like viruses. The SBPV capsid protein VP3 has a large C terminal domain, five of which form highly prominent protruding "crowns" on the virion surface. However, the domains can change their positions depending on the conditions of the environment. The domain includes a putative catalytic or receptor binding site that might be important for SBPV cell entry. PMID- 27279611 TI - Arabidopsis RNA Polymerases IV and V Are Required To Establish H3K9 Methylation, but Not Cytosine Methylation, on Geminivirus Chromatin. AB - In plants, RNA-directed DNA methylation (RdDM) employs small RNAs to target enzymes that methylate cytosine residues. Cytosine methylation and dimethylation of histone 3 lysine 9 (H3K9me2) are often linked. Together they condition an epigenetic defense that results in chromatin compaction and transcriptional silencing of transposons and viral chromatin. Canonical RdDM (Pol IV-RdDM), involving RNA polymerases IV and V (Pol IV and Pol V), was believed to be necessary to establish cytosine methylation, which in turn could recruit H3K9 methyltransferases. However, recent studies have revealed that a pathway involving Pol II and RNA-dependent RNA polymerase 6 (RDR6) (RDR6-RdDM) is likely responsible for establishing cytosine methylation at naive loci, while Pol IV RdDM acts to reinforce and maintain it. We used the geminivirus Beet curly top virus (BCTV) as a model to examine the roles of Pol IV and Pol V in establishing repressive viral chromatin methylation. As geminivirus chromatin is formed de novo in infected cells, these viruses are unique models for processes involved in the establishment of epigenetic marks. We confirm that Pol IV and Pol V are not needed to establish viral DNA methylation but are essential for its amplification. Remarkably, however, both Pol IV and Pol V are required for deposition of H3K9me2 on viral chromatin. Our findings suggest that cytosine methylation alone is not sufficient to trigger de novo deposition of H3K9me2 and further that Pol IV-RdDM is responsible for recruiting H3K9 methyltransferases to viral chromatin. IMPORTANCE: In plants, RNA-directed DNA methylation (RdDM) uses small RNAs to target cytosine methylation, which is often linked to H3K9me2. These epigenetic marks silence transposable elements and DNA virus genomes, but how they are established is not well understood. Canonical RdDM, involving Pol IV and Pol V, was thought to establish cytosine methylation that in turn could recruit H3K9 methyltransferases, but recent studies compel a reevaluation of this view. We used BCTV to investigate the roles of Pol IV and Pol V in chromatin methylation. We found that both are needed to amplify, but not to establish, DNA methylation. However, both are required for deposition of H3K9me2. Our findings suggest that cytosine methylation is not sufficient to recruit H3K9 methyltransferases to naive viral chromatin and further that Pol IV-RdDM is responsible. PMID- 27279612 TI - A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats. AB - Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (DeltaSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-DeltaSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log10 total PFU and 2.7 log10 PFU/g of tissue, respectively, compared to those in unvaccinated animals (P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. IMPORTANCE: RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by incorporating a low-fusion, subgroup B F protein in the genetic background of codon-deoptimized nonstructural protein genes and a deleted small hydrophobic protein gene. The resultant vaccine candidate, DB1, was attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. PMID- 27279613 TI - 1H Nuclear Magnetic Resonance Metabolomics of Plasma Unveils Liver Dysfunction in Dengue Patients. AB - Dengue, due to its global burden, is the most important arthropod-borne flavivirus disease, and early detection lowers fatality rates to below 1%. Since the metabolic resources crucial for viral replication are provided by host cells, detection of changes in the metabolic profile associated with disease pathogenesis could help with the identification of markers of prognostic and diagnostic importance. We applied (1)H nuclear magnetic resonance exploratory metabolomics to study longitudinal changes in plasma metabolites in a cohort in Recife, Brazil. To gain statistical power, we used innovative paired multivariate analyses to discriminate individuals with primary and secondary infection presenting as dengue fever (DF; mild) and dengue hemorrhagic fever (DHF; severe) and subjects with a nonspecific nondengue (ND) illness (ND subjects). Our results showed that a decrease in plasma low-density lipoprotein (LDL) and very-low density lipoprotein (VLDL) discriminated dengue virus (DENV)-infected subjects from ND subjects, and also, subjects with severe infection even presented a decrease in lipoprotein concentrations compared to the concentrations in subjects with mild infection. These results add to the ongoing discussion that the manipulation of lipid metabolism is crucial for DENV replication and infection. In addition, a decrease in plasma glutamine content was characteristic of DENV infection and disease severity, and an increase in plasma acetate levels discriminated subjects with DF and DHF from ND subjects. Several other metabolites shown to be altered in DENV infection and the implications of these alterations are discussed. We hypothesize that these changes in the plasma metabolome are suggestive of liver dysfunction, could provide insights into the underlying molecular mechanisms of dengue virus pathogenesis, and could help to discriminate individuals at risk of the development of severe infection and predict disease outcome. IMPORTANCE: Dengue, due to its global burden, is the most important mosquito-borne viral disease. There is no specific treatment for dengue disease, and early detection lowers fatality rates to below 1%. In this study, we observed the effects of dengue virus infection on the profile of small molecules in the blood of patients with mild and severe infection. Variations in the profiles of these small molecules reflected the replication of dengue virus in different tissues and the extent of tissue damage during infection. The results of this study showed that the molecules that changed the most were VLDL, LDL, and amino acids. We propose that these changes reflect liver dysfunction and also that they can be used to discriminate subjects with mild dengue from those with severe dengue. PMID- 27279614 TI - Antiretroviral Therapy in Simian Immunodeficiency Virus-Infected Sooty Mangabeys: Implications for AIDS Pathogenesis. AB - Simian immunodeficiency virus (SIV)-infected sooty mangabeys (SMs) do not develop AIDS despite high levels of viremia. Key factors involved in the benign course of SIV infection in SMs are the absence of chronic immune activation and low levels of infection of CD4(+) central memory (TCM) and stem cell memory (TSCM) T cells. To better understand the role of virus replication in determining the main features of SIV infection in SMs, we treated 12 SMs with a potent antiretroviral therapy (ART) regimen for 2 to 12 months. We observed that ART suppressed viremia to <60 copies/ml of plasma in 10 of 12 animals and induced a variable decrease in the level of cell-associated SIV DNA in peripheral blood (average changes of 0.9 , 1.1-, 1.5-, and 3.7-fold for CD4(+) transitional memory [TTM], TCM, effector memory [TEM], and TSCM cells, respectively). ART-treated SIV-infected SMs showed (i) increased percentages of circulating CD4(+) TCM cells, (ii) increased levels of CD4(+) T cells in the rectal mucosa, and (iii) significant declines in the frequencies of HLA-DR(+) CD8(+) T cells in the blood and rectal mucosa. In addition, we observed that ART interruption resulted in rapid viral rebound in all SIV-infected SMs, indicating that the virus reservoir persists for at least a year under ART despite lower infection levels of CD4(+) TCM and TSCM cells than those seen in pathogenic SIV infections of macaques. Overall, these data indicate that ART induces specific immunological changes in SIV-infected SMs, thus suggesting that virus replication affects immune function even in the context of this clinically benign infection. IMPORTANCE: Studies of natural, nonpathogenic simian immunodeficiency virus (SIV) infection of African monkeys have provided important insights into the mechanisms responsible for the progression to AIDS during pathogenic human immunodeficiency virus (HIV) infection of humans and SIV infection of Asian macaques. In this study, for the first time, we treated SIV infected sooty mangabeys, a natural host for the infection, with a potent antiretroviral therapy (ART) regimen for periods ranging from 2 to 12 months and monitored in detail how suppression of virus replication affected the main virological and immunological features of this nonpathogenic infection. The observed findings provide novel information on both the pathogenesis of residual immunological disease under ART during pathogenic infection and the mechanisms involved in virus persistence during primate lentiviral infections. PMID- 27279615 TI - RNA Binding of Ebola Virus VP30 Is Essential for Activating Viral Transcription. AB - The template for Ebola virus (EBOV) transcription and replication is the helical viral nucleocapsid composed of the viral negative-sense (-) RNA genome, which is complexed by the nucleoprotein (NP), VP35, polymerase L, VP24, and VP30. While viral replication is exerted by polymerase L and its cofactor VP35, EBOV mRNA synthesis is regulated by the viral nucleocapsid protein VP30, an essential EBOV specific transcription factor. VP30 is a homohexameric phosphoprotein containing a nonconventional zinc finger. The transcriptional support activity of VP30 is strongly influenced by its phosphorylation state. We studied here how RNA binding contributed to VP30's function in transcriptional activation. Using a novel mobility shift assay and the 3'-terminal 154 nucleotides of the EBOV genome as a standard RNA substrate, we detected that RNA binding of VP30 was severely impaired by VP30 mutations that (i) destroy the protein's capability to form homohexamers, (ii) disrupt the integrity of its zinc finger domain, (iii) mimic its fully phosphorylated state, or (iv) alter the putative RNA binding region. RNA binding of the mutant VP30 proteins correlated strongly with their transcriptional support activity. Furthermore, we showed that the interaction between VP30 and the polymerase cofactor VP35 is RNA dependent, while formation of VP30 homohexamers and VP35 homotetramers is not. Our data indicate that RNA binding of VP30 is essential for its transcriptional support activity and stabilizes complexes of VP35/L polymerase with the (-) RNA template to favor productive transcriptional initiation in the presence of termination-active RNA secondary structures. IMPORTANCE: Ebola virus causes severe fevers with unusually high case fatality rates. The recent outbreak of Ebola virus in West Africa claimed more than 11,000 lives and threatened to destabilize a whole region because of its dramatic effects on the public health systems. It is currently not completely understood how Ebola virus manages to balance viral transcription and replication in the infected cells. This study shows that transcriptional support activity of the Ebola virus transcription factor VP30 is highly correlated with its ability to bind viral RNA. The interaction between VP30 and VP35, the Ebola virus polymerase cofactor, is dependent on the presence of RNA as well. Our data contribute to the understanding of the dynamic interplay between nucleocapsid proteins and the viral RNA template in order to promote viral RNA synthesis. PMID- 27279616 TI - Coinfection with Human Cytomegalovirus Genetic Variants in Transplant Recipients and Its Impact on Antiviral T Cell Immune Reconstitution. AB - Reconstitution of T cell immunity is absolutely critical for the effective control of virus-associated infectious complications in hematopoietic stem cell transplant (HSCT) recipients. Coinfection with genetic variants of human cytomegalovirus (CMV) in transplant recipients has been linked to clinical disease manifestation; however, how these genetic variants impact T cell immune reconstitution remains poorly understood. In this study, we have evaluated dynamic changes in the emergence of genetic variants of CMV in HSCT recipients and correlated these changes with reconstitution of antiviral T cell responses. In an analysis of single nucleotide polymorphisms within sequences encoding HLA class I-restricted CMV epitopes from the immediate early 1 gene of CMV, coinfection with genetically distinct variants of CMV was detected in 52% of patients. However, in spite of exposure to multiple viral variants, the T cell responses in these patients were preferentially directed to a limited repertoire of HLA class I-restricted CMV epitopes, either conserved, variant, or cross reactive. More importantly, we also demonstrate that long-term control of CMV infection after HSCT is primarily mediated through the efficient induction of stable antiviral T cell immunity irrespective of the nature of the antigenic target. These observations provide important insights for the future design of antiviral T cell-based immunotherapeutic strategies for transplant recipients, emphasizing the critical impact of robust immune reconstitution on efficient control of viral infection. IMPORTANCE: Infection and disease caused by human cytomegalovirus (CMV) remain a significant burden in patients undergoing hematopoietic stem cell transplantation (HSCT). The establishment of efficient immunological control, primarily mediated by cytotoxic T cells, plays a critical role in preventing CMV-associated disease in transplant recipients. Recent studies have also begun to investigate the impact genetic variation in CMV has upon disease outcome in transplant recipients. In this study, we sought to investigate the role T cell immunity plays in recognizing and controlling genetic variants of CMV. We demonstrate that while a significant proportion of HSCT recipients may be exposed to multiple genetic variants of CMV, this does not necessarily lead to immune control mediated via recognition of this genetic variation. Rather, immune control is associated with the efficient establishment of a stable immune response predominantly directed against immunodominant conserved T cell epitopes. PMID- 27279617 TI - Changes in HIV-1 Capsid Stability Induced by Common Cytotoxic-T-Lymphocyte-Driven Viral Sequence Mutations. AB - HIV-1-infected individuals with protective HLA class I alleles exhibit better control of viremia and slower disease progression. Virus control in these individuals has been associated with strong and potent HIV-1-specific cytotoxic-T lymphocyte (CTL) responses restricted by protective HLA alleles, but control of viremia also occurs in the presence of selected CTL escape mutations. CTL escape mutations restricted by protective HLA class I molecules are frequently located in the conserved p24 Gag sequence of HIV-1 that encodes the conical capsid core and have been suggested to reduce viral replication capacity. In this study, the consequences of well-described CTL-associated p24 Gag sequence mutations for HIV 1 capsid stability were assessed using a cyclosporine (CsA) washout assay. The frequently occurring HLA-B57- and HLA-B27-associated CTL escape mutations T242N and R264K resulted in delayed capsid uncoating, suggesting modulation of capsid stability. The described compensatory mutations L268M and S173A observed in R264K viruses reconstituted the capsid-uncoating half-time. Interestingly, capsid stability was correlated with infectivity. Taken together, these data demonstrate that CTL-driven escape mutations within p24 Gag restricted by protective HLA class I alleles have a significant impact on capsid stability that might contribute to the persistent control of viral replication observed despite viral escape from CTL responses. IMPORTANCE: Sequence mutations within p24 Gag selected by CTL responses restricted by protective HLA class I alleles have been associated with reduced viral fitness. However, the precise mechanisms underlying the reduced viral replication capacity and lower viral loads associated with these mutations remain unclear. Here, we demonstrate that dominant HLA-B27 associated CTL escape mutations within HIV-1 capsid lead to enhanced capsid rigidity, providing a possible mechanism for the reduced viral fitness of these variants. PMID- 27279618 TI - Infectious Bronchitis Coronavirus Limits Interferon Production by Inducing a Host Shutoff That Requires Accessory Protein 5b. AB - During infection of their host cells, viruses often inhibit the production of host proteins, a process that is referred to as host shutoff. By doing this, viruses limit the production of antiviral proteins and increase production capacity for viral proteins. Coronaviruses from the genera Alphacoronavirus and Betacoronavirus, such as severe acute respiratory syndrome coronavirus (SARS CoV), establish host shutoff via their nonstructural protein 1 (nsp1). The Gammacoronavirus and Deltacoronavirus genomes, however, do not encode nsp1, and it has been suggested that these viruses do not induce host shutoff. Here, we show that the Gammacoronavirus infectious bronchitis virus (IBV) does induce host shutoff, and we find that its accessory protein 5b is indispensable for this function. Importantly, we found that 5b-null viruses, unlike wild-type viruses, induce production of high concentrations of type I interferon protein in vitro, indicating that host shutoff by IBV plays an important role in antagonizing the host's innate immune response. Altogether, we demonstrate that 5b is a functional equivalent of nsp1, thereby answering the longstanding question of whether lack of nsp1 in gammacoronaviruses is compensated for by another viral protein. As such, our study is a significant step forward in the understanding of coronavirus biology and closes a gap in the understanding of some IBV virulence strategies. IMPORTANCE: Many viruses inhibit protein synthesis by their host cell to enhance virus replication and to antagonize antiviral defense mechanisms. This process is referred to as host shutoff. We studied gene expression and protein synthesis in chicken cells infected with the important poultry pathogen infectious bronchitis virus (IBV). We show that IBV inhibits synthesis of host proteins, including that of type I interferon, a key component of the antiviral response. The IBV-induced host shutoff, however, does not require degradation of host RNA. Furthermore, we demonstrate that accessory protein 5b of IBV plays a crucial role in the onset of host shutoff. Our findings suggest that inhibition of host protein synthesis is a common feature of coronaviruses and primarily serves to inhibit the antiviral response of the host. PMID- 27279619 TI - Pandemic Seasonal H1N1 Reassortants Recovered from Patient Material Display a Phenotype Similar to That of the Seasonal Parent. AB - We have previously shown that 11 patients became naturally coinfected with seasonal H1N1 (A/H1N1) and pandemic H1N1 (pdm/H1N1) during the Southern hemisphere winter of 2009 in New Zealand. Reassortment of influenza A viruses is readily observed during coinfection of host animals and in vitro; however, reports of reassortment occurring naturally in humans are rare. Using clinical specimen material, we show reassortment between the two coinfecting viruses occurred with high likelihood directly in one of the previously identified patients. Despite the lack of spread of these reassortants in the community, we did not find them to be attenuated in several model systems for viral replication and virus transmission: multistep growth curves in differentiated human bronchial epithelial cells revealed no growth deficiency in six recovered reassortants compared to A/H1N1 and pdm/H1N1 isolates. Two reassortant viruses were assessed in ferrets and showed transmission to aerosol contacts. This study demonstrates that influenza virus reassortants can arise in naturally coinfected patients. IMPORTANCE: Reassortment of influenza A viruses is an important driver of virus evolution, but little has been done to address humans as hosts for the generation of novel influenza viruses. We show here that multiple reassortant viruses were generated during natural coinfection of a patient with pandemic H1N1 (2009) and seasonal H1N1 influenza A viruses. Though apparently fit in model systems, these reassortants did not become established in the wider population, presumably due to herd immunity against their seasonal H1 antigen. PMID- 27279620 TI - Role for the alphaV Integrin Subunit in Varicella-Zoster Virus-Mediated Fusion and Infection. AB - Varicella-zoster virus (VZV) is an alphaherpesvirus that causes varicella and herpes zoster. Membrane fusion is essential for VZV entry and the distinctive syncytium formation in VZV-infected skin and neuronal tissue. Herpesvirus fusion is mediated by a complex of glycoproteins gB and gH-gL, which are necessary and sufficient for VZV to induce membrane fusion. However, the cellular requirements of fusion are poorly understood. Integrins have been implicated to facilitate entry of several human herpesviruses, but their role in VZV entry has not yet been explored. To determine the involvement of integrins in VZV fusion, a quantitative cell-cell fusion assay was developed using a VZV-permissive melanoma cell line. The cells constitutively expressed a reporter protein and short hairpin RNAs (shRNAs) to knock down the expression of integrin subunits shown to be expressed in these cells by RNA sequencing. The alphaV integrin subunit was identified as mediating VZV gB/gH-gL fusion, as its knockdown by shRNAs reduced fusion levels to 60% of that of control cells. A comparable reduction in fusion levels was observed when an anti-alphaV antibody specific to its extracellular domain was tested in the fusion assay, confirming that the domain was important for VZV fusion. In addition, reduced spread was observed in alphaV knockdown cells infected with the VZV pOka strain relative to that of the control cells. This was demonstrated by reductions in plaque size, replication kinetics, and virion entry in the alphaV subunit knockdown cells. Thus, the alphaV integrin subunit is important for VZV gB/gH-gL fusion and infection. IMPORTANCE: Varicella zoster virus (VZV) is a highly infectious pathogen that causes chickenpox and shingles. A common complication of shingles is the excruciating condition called postherpetic neuralgia, which has proven difficult to treat. While a vaccine is now available, it is not recommended for immunocompromised individuals and its efficacy decreases with the recipient's age. These limitations highlight the need for new therapies. This study examines the role of integrins in membrane fusion mediated by VZV glycoproteins gB and gH-gL, a required process for VZV infection. This knowledge will further the understanding of VZV entry and provide insight into the development of better therapies. PMID- 27279621 TI - Spatial-Temporal Patterns of Viral Amplification and Interference Initiated by a Single Infected Cell. AB - When viruses infect their host cells, they can make defective virus-like particles along with intact virus. Cells coinfected with virus and defective particles often exhibit interference with virus growth caused by the competition for resources by defective genomes. Recent reports of the coexistence and cotransmission of such defective interfering particles (DIPs) in vivo, across epidemiological length and time scales, suggest a role in viral pathogenesis, but it is not known how DIPs impact infection spread, even under controlled culture conditions. Using fluorescence microscopy, we quantified coinfections of vesicular stomatitis virus (VSV) expressing a fluorescent reporter protein and its DIPs on BHK-21 host cell monolayers. We found that viral gene expression was more delayed, infections spread more slowly, and patterns of spread became more "patchy" with higher DIP inputs to the initial cell. To examine how infection spread might depend on the behavior of the initial coinfected cell, we built a computational model, adapting a cellular automaton (CA) approach to incorporate kinetic data on virus growth for the first time. Specifically, changes in observed patterns of infection spread could be directly linked to previous high throughput single-cell measures of virus-DIP coinfection. The CA model also provided testable hypotheses on the spatial-temporal distribution of the DIPs, which remain governed by their predator-prey interaction. More generally, this work offers a data-driven computational modeling approach for better understanding of how single infected cells impact the multiround spread of virus infections across cell populations. IMPORTANCE: Defective interfering particles (DIPs) compete with intact virus, depleting host cell resources that are essential for virus growth and infection spread. However, it is not known how such competition, strong or weak, ultimately affects the way in which infections spread and cause disease. In this study, we address this unmet need by developing an integrated experimental-computational approach, which sheds new light on how infections spread. We anticipate that our approach will also be useful in the development of DIPs as therapeutic agents to manage the spread of viral infections. PMID- 27279622 TI - Mapping of Ebolavirus Neutralization by Monoclonal Antibodies in the ZMapp Cocktail Using Cryo-Electron Tomography and Studies of Cellular Entry. AB - ZMapp, a cocktail of three monoclonal antibodies (MAbs; c2G4, c4G7, and c13C6) against the ebolavirus (EBOV) glycoprotein (GP), shows promise for combatting outbreaks of EBOV, as occurred in West Africa in 2014. Prior studies showed that Fabs from these MAbs bind a soluble EBOV GP ectodomain and that MAbs c2G4 and c4G7, but not c13C6, neutralize infections in cell cultures. Using cryo-electron tomography, we extended these findings by characterizing the structures of c2G4, c4G7, and c13C6 IgGs bound to native, full-length GP from the West African 2014 isolate embedded in filamentous viruslike particles (VLPs). As with the isolated ectodomain, c13C6 bound to the glycan cap, whereas c2G4 and c4G7 bound to the base region of membrane-bound GP. The tomographic data suggest that all three MAbs bind with high occupancy and that the base-binding antibodies can potentially bridge neighboring GP spikes. Functional studies indicated that c2G4 and c4G7, but not c13C6, competitively inhibit entry of VLPs bearing EBOV GP into the host cell cytoplasm, without blocking trafficking of VLPs to NPC1(+) endolysosomes, where EBOV fuses. Moreover, c2G4 and c4G7 bind to and can block entry mediated by the primed (19-kDa) form of GP without impeding binding of the C-loop of NPC1, the endolysosomal receptor for EBOV. The most likely mode of action of c2G4 and c4G7 is therefore by inhibiting conformational changes in primed, NPC1-bound GP that initiate fusion between the viral and target membranes, similar to the action of certain broadly neutralizing antibodies against influenza hemagglutinin and HIV Env. IMPORTANCE: The recent West African outbreak of ebolavirus caused the deaths of more than 11,000 individuals. Hence, there is an urgent need to be prepared with vaccines and therapeutics for similar future disasters. ZMapp, a cocktail of three MAbs directed against the ebolavirus glycoprotein, is a promising anti-ebolavirus therapeutic. Using cryo-electron tomography, we provide structural information on how each of the MAbs in this cocktail binds to the ebolavirus glycoprotein as it is displayed-embedded in the membrane and present at high density-on filamentous viruslike particles that recapitulate the surface structure and entry functions of ebolavirus. Moreover, after confirming that two of the MAbs bind to the same region in the base of the glycoprotein, we show that they competitively block the entry function of the glycoprotein and that they can do so after the glycoprotein is proteolytically primed and bound to its intracellular receptor, Niemann-Pick C1. These findings should inform future developments of ebolavirus therapeutics. PMID- 27279623 TI - Evidence that Receptor Destruction by the Sendai Virus Hemagglutinin Neuraminidase Protein Is Responsible for Homologous Interference. AB - Receptor destruction has been considered one of the mechanisms of homologous Sendai virus (SeV) interference. However, direct evidence of receptor destruction upon virus infection and its relevance to interference is missing. To investigate a precise mechanism of homologous interference, we established SeV persistently infected cells. The persistently infected cells inhibited superinfection by homologous SeV but supported replication of human parainfluenza virus 2 (hPIV2) and influenza A virus (IAV). We confirmed that SeV particles could not attach to or penetrate the infected cells and that the hemagglutinin-neuraminidase (HN) protein of SeV was involved in the interference. Lectin blot assays showed that the alpha2,3-linked sialic acids were specifically reduced in the SeV-infected cells, but the level of alpha2,6-linked sialic acids had not changed. As infection with IAV removed both alpha2,3- and alpha2,6-linked sialic acids, especially alpha2,3-linked sialic acids, IAV-infected cells inhibited superinfection of SeV. These results provide concrete evidence that destruction of the specific SeV receptor, alpha2,3-linked sialic acids, is relevant to homologous interference by SeV. IMPORTANCE: Viral interference is a classically observed phenomenon, but the precise mechanism is not clear. Using SeV interference, we provide concrete evidence that reduction of the alpha2,3-linked sialic acid receptor by the HN of SeV is closely related with viral interference. Since SeV infection resulted in decrease of only alpha2,3-linked sialic acids, IAV, which also utilized alpha2,6-linked sialic acids to initiate infection, superinfected the SeV-infected cells. In contrast, SeV could not superinfect the IAV-infected cells because both alpha2,3- and alpha2,6-linked sialic acids were removed. These results indicate that receptor destruction critically contributes to viral interference. PMID- 27279625 TI - Heavy metal resistance in halophilic Bacteria and Archaea. AB - Heavy metals are dense chemicals with dual biological role as micronutrients and intoxicants. A few hypersaline environmental systems are naturally enriched with heavy metals, while most metal-contaminated sites are a consequence of human activities. Numerous halotolerant and moderately halophilic Bacteria possess metal tolerance, whereas a few archaeal counterparts share similar features. The main mechanisms underlying heavy metal resistance in halophilic Bacteria and Archaea include extracellular metal sequestration by biopolymers, metal efflux mediated by specific transporters and enzymatic detoxification. Biotransformation of metals by halophiles has implications both for trace metal turnover in natural saline ecosystems and for development of novel bioremediation strategies. PMID- 27279624 TI - Structure and Genome Release Mechanism of the Human Cardiovirus Saffold Virus 3. AB - In order to initiate an infection, viruses need to deliver their genomes into cells. This involves uncoating the genome and transporting it to the cytoplasm. The process of genome delivery is not well understood for nonenveloped viruses. We address this gap in our current knowledge by studying the uncoating of the nonenveloped human cardiovirus Saffold virus 3 (SAFV-3) of the family Picornaviridae SAFVs cause diseases ranging from gastrointestinal disorders to meningitis. We present a structure of a native SAFV-3 virion determined to 2.5 A by X-ray crystallography and an 11-A-resolution cryo-electron microscopy reconstruction of an "altered" particle that is primed for genome release. The altered particles are expanded relative to the native virus and contain pores in the capsid that might serve as channels for the release of VP4 subunits, N termini of VP1, and the RNA genome. Unlike in the related enteroviruses, pores in SAFV-3 are located roughly between the icosahedral 3- and 5-fold axes at an interface formed by two VP1 and one VP3 subunit. Furthermore, in native conditions many cardioviruses contain a disulfide bond formed by cysteines that are separated by just one residue. The disulfide bond is located in a surface loop of VP3. We determined the structure of the SAFV-3 virion in which the disulfide bonds are reduced. Disruption of the bond had minimal effect on the structure of the loop, but it increased the stability and decreased the infectivity of the virus. Therefore, compounds specifically disrupting or binding to the disulfide bond might limit SAFV infection. IMPORTANCE: A capsid assembled from viral proteins protects the virus genome during transmission from one cell to another. However, when a virus enters a cell the virus genome has to be released from the capsid in order to initiate infection. This process is not well understood for nonenveloped viruses. We address this gap in our current knowledge by studying the genome release of Human Saffold virus 3 Saffold viruses cause diseases ranging from gastrointestinal disorders to meningitis. We show that before the genome is released, the Saffold virus 3 particle expands, and holes form in the previously compact capsid. These holes serve as channels for the release of the genome and small capsid proteins VP4 that in related enteroviruses facilitate subsequent transport of the virus genome into the cell cytoplasm. PMID- 27279626 TI - Millimeter scale electron conduction through exoelectrogenic mixed species biofilms. AB - The functioning of many natural and engineered environments is dependent on long distance electron transfer mediated through electrical currents. These currents have been observed in exoelectrogenic biofilms and it has been proposed that microbial biofilms can mediate electron transfer via electrical currents on the centimeter scale. However, direct evidence to confirm this hypothesis has not been demonstrated and the longest known electrical transfer distance for single species exoelectrogenic biofilms is limited to 100 MUm. In the present study, biofilms were developed on electrodes with electrically non-conductive gaps from 50 MUm to 1 mm and the in situ conductance of biofilms was evaluated over time. Results demonstrated that the exoelectrogenic mixed species biofilms in the present study possess the ability to transfer electrons through electrical currents over a distance of up to 1 mm, 10 times further than previously observed. Results indicate the possibility of interspecies interactions playing an important role in the spatial development of exoelectrogenic biofilms, suggesting that these biological networks might remain conductive even at longer distance. These findings have significant implications in regards to future optimization of microbial electrochemical systems. PMID- 27279627 TI - Auranofin and N-heterocyclic carbene gold-analogs are potent inhibitors of the bacteria Helicobacter pylori. AB - Auranofin is an FDA-approved gold-containing compound used for the treatment of rheumatoid arthritis. Recent reports of antimicrobial activity against protozoa and bacteria indicate that auranofin targets the reductive enzyme thioredoxin reductase (TrxR). We evaluated auranofin as well as five auranofin analogs containing N-heterocyclic carbenes (instead of the triethylphosphane present in auranofin) and five gold-carbene controls for their ability to inhibit or kill Helicobacter pylori in vitro Auranofin completely inhibited bacterial growth at 1.2 MUM. Purified H. pylori TrxR was inhibited by auranofin in a cell-free assay (IC50 ~88 nM). The most active gold(I)-N-heterocyclic carbene compounds exhibited MICs comparable to auranofin against H. pylori (2 MUM), while also exhibiting lower toxicities for human embryonic kidney cells (HEK-293T cells). Median toxic concentrations (TC50) were 13-20-fold higher compared to auranofin indicating that they were less cytotoxic. The N-heterocyclic carbene analogs maybe well tolerated, but further evaluation is needed in vivo Finally, auranofin was synergistic with the antibiotic amoxicillin, suggesting that targeting both the reductive enzyme TrxR and cell wall synthesis may be effective against H. pylori infections. PMID- 27279628 TI - Endosymbiotic bacteria in honey bees: Arsenophonus spp. are not transmitted transovarially. AB - Intracellular endosymbiotic bacteria are common and can play a crucial role for insect pathology. Therefore, such bacteria could be a potential key to our understanding of major losses of Western honey bees (Apis mellifera) colonies. However, the transmission and potential effects of endosymbiotic bacteria in A. mellifera and other Apis spp. are poorly understood. Here, we explore the prevalence and transmission of the genera Arsenophonus, Wolbachia, Spiroplasma and Rickettsia in Apis spp. Colonies of A. mellifera (N = 33, with 20 eggs from worker brood cells and 100 adult workers each) as well as mated honey bee queens of A. cerana, A. dorsata and A. florea (N = 12 each) were screened using PCR. While Wolbachia, Spiroplasma and Rickettsia were not detected, Arsenophonus spp. were found in 24.2% of A. mellifera colonies and respective queens as well as in queens of A. dorsata (8.3%) and A. florea (8.3%), but not in A. cerana The absence of Arsenophonus spp. from reproductive organs of A. mellifera queens and surface-sterilized eggs does not support transovarial vertical transmission. Instead, horizontal transmission is most likely. PMID- 27279630 TI - Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice. AB - The third generation aromatase inhibitors are currently the drugs of choice for the treatment of early and advanced breast cancer in postmenopausal women. One of the significant limiting factor during therapy is their negative impact on bone health. In this study, we compared the effects of a nonsteroidal (letrozole) and a steroidal aromatase inhibitor (exemestane) on bone mineral density and markers of bone turnover including alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), hydroxyproline (HxP), receptor activator of nuclear factor kappa B ligand (RANKL), sclerostin, and dickkopf-1 (DKK-1) in vinylcyclohexene diepoxide (VCD)-induced ovotoxic female mice. VCD administration for 15 days mimicked a postmenopausal state with reduced serum estradiol levels. Ovotoxicity was accompanied by reduced ALP, HxP and enhanced TRAP, sclerostin and DKK-1 activity in femoral epiphysis and lumbar vertebrae of mice. While letrozole (1 mg/kg) administration for 1 month enhanced bone turnover in ovotoxic mice, exemestane (3.25 mg/kg) was devoid of such effects in both normal and ovotoxic mice. The latter, however, reduced ALP in femoral epiphysis of ovotoxic mice. Letrozole depleted estradiol levels in ovotoxic mice and enhanced RANKL activity while exemestane neither affected estradiol nor RANKL in both normal and ovotoxic mice, and enhanced sclerostin and DKK-1 in femoral epiphysis only. The study indicates that the two aromatase inhibitors possesses differential profile in terms of their effects on bone and that exemestane could be a better option for the treatment of breast cancer in postmenopausal women at least in terms of its effects on bone. PMID- 27279629 TI - Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/beta-catenin pathway activity. AB - To investigate the mitigation effect and mechanism of oestrogen and PTH on disc degeneration in rats after ovariectomy, as well as on Wnt/beta-catenin pathway activity, thirty 3-month-old rats were ovariectomized and divided into three groups. Ten additional rats were used as controls. Eight weeks later, the rats were administered oestrogen or PTH for 12 weeks, and then discs were collected for tests. Results showed that nucleus pulposus cells in the Sham group were mostly notochord cells, while in the OVX group, cells gradually developed into chondrocyte-like cells. Oestrogen or PTH could partly recover the notochord cell number. After ovariectomy, the endplate roughened and endplate porosity decreased. After oestrogen or PTH treatment, the smoothness and porosity of endplate recovered. Compared with the Sham group, Aggrecan, Col2a and Wnt/beta catenin pathway expression in OVX group decreased, and either oestrogen or PTH treatment improved their expression. The biomechanical properties of intervertebral disc significantly changed after ovariectomy, and oestrogen or PTH treatment partly recovered them. Disc degeneration occurred with low oestrogen, and the underlying mechanisms involve nutrition supply disorders, cell type changes and decreased Wnt/beta-catenin pathway activity. Oestrogen and PTH can retard disc degeneration in OVX rats and enhance Wnt/beta-catenin pathway activity in nucleus pulposus. PMID- 27279631 TI - Enhanced osteoprogenitor elongated collagen fiber matrix formation by bioactive glass ionic silicon dependent on Sp7 (osterix) transcription. AB - Bioactive glasses release ions, those enhance osteoblast collagen matrix synthesis and osteogenic marker expression during bone healing. Collagen matrix density and osteogenic marker expression depend on osteogenic transcription factors, (e.g., Osterix (OSX)). We hypothesize that enhanced expression and formation of collagen by Si(4+) depends on enhanced expression of OSX transcription. Experimental bioactive glass (6P53-b) and commercial Bioglass(TM) (45S5) were dissolved in basal medium to make glass conditioned medium (GCM). ICP MS analysis was used to measure bioactive glass ion release rates. MC3T3-E1 cells were cultured for 20 days, and gene expression and extracellular matrix collagen formation was analyzed. In a separate study, siRNA was used to determine the effect of OSX knockdown on impacting the effect of Si(4+) on osteogenic markers and matrix collagen formation. Each bioactive glass exhibited similar ion release rates for all ions, except Mg(2+) released by 6P53-b. Gene expression results showed that GCM markedly enhanced many osteogenic markers, and 45S5 GCM showed higher levels of expression and collagen matrix fiber bundle density than 6P53-b GCM. Upon knockdown of OSX transcription, collagen type 5, alkaline phosphatase, and matrix density were not enhanced as compared to wild type cells. This study illustrates that the enhancement of elongated collagen fiber matrix formation by Si(+/-) depends on OSX transcription. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2604-2615, 2016. PMID- 27279632 TI - Characterization of ApB73, a virulence factor important for colonization of Zea mays by the smut Ustilago maydis. AB - The biotrophic fungus Ustilago maydis, the causal agent of corn smut disease, uses numerous small secreted effector proteins to suppress plant defence responses and reshape the host metabolism. However, the role of specific effectors remains poorly understood. Here, we describe the identification of ApB73 (Apathogenic in B73), an as yet uncharacterized protein essential for the successful colonization of maize by U. maydis. We show that apB73 is transcriptionally induced during the biotrophic stages of the fungal life cycle. The deletion of the apB73 gene results in cultivar-specific loss of gall formation in the host. The ApB73 protein is conserved among closely related smut fungi. However, using virulence assays, we show that only the orthologue of the maize-infecting head smut Sporisorium reilianum can complement the mutant phenotype of U. maydis. Although microscopy shows that ApB73 is secreted into the biotrophic interface, it seems to remain associated with fungal cell wall components or the fungal plasma membrane. Taken together, the results show that ApB73 is a conserved and important virulence factor of U. maydis that localizes to the interface between the pathogen and its host Zea mays. PMID- 27279633 TI - Aldehyde dehydrogenase 3A1 is robustly upregulated in gastric cancer stem-like cells and associated with tumorigenesis. AB - Enhanced aldehyde dehydrogenase (ALDH) activity has been shown to serve as a hallmark for cancer stem cells (CSCs). Recent evidence suggests that its role as a stem cell-related marker has come down to the specific isoform. However, little is known about the specific ALDH isoform contributing to aldefluor activity in gastric cancer. In this study, we isolated ALDHbright cells from 2 human gastric cancer cell lines MKN-45 and SGC-7901 by using an Aldefluor assay and found elevated self-renewal, differentiation and tumorigenicity, as demonstration of stemness characteristics. We also found that ALDHbright cells expressed decreased levels of E-cadherin but increased levels of Snail and Vimentin, indication of an epithelial-mesenchymal transition (EMT) phenotype which may be responsible for the enhanced metastatic potential. Since further research and prognostic application based on ALDH prevalence require the quantification of the specific ALDH isoform, we characterized the expression of all 19 ALDH isoforms in the sorted gastric cancer cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). Compared with the non-stem counterparts, robust upregulation of ALDH-3A1 was observed in these gastric cancer stem-like cells. Furthermore, we performed immunohistological analysis on 93 fixed patient gastric tumor samples and found that ALDH-3A1 expression correlated well with gastric cancer dysplasia and grades, differentiation, lymph node metastasis and cancer stage. Our data, therefore, provide strong evidence that ALDH-3A1 is a novel gastric cancer stem cell related marker with potential prognostic values and demonstrate a clear association between ALDH-3A1 prevalence and gastric cancer progression. PMID- 27279634 TI - Squamous Cell Carcinoma In Situ of the Breast: Report of a Case. AB - We present the case of a 73-year-old woman with pure squamous cell carcinoma in situ of the left breast. This non-invasive malignancy exhibited pure squamous type of architectural and cytologic features without any evidence of glandular differentiation either in the initial needle core biopsy or in the subsequently performed excisional biopsy and simple mastectomy. The tumor spanned 1.6 cm, involved numerous ducts and terminal ducts and extended into lobules, and was characterized by keratinizing squamous cells with intermediate-grade nuclei. Intercellular bridges extended between the malignant squamous cells. Keratinous debris with "pearl" formation was evident in most involved glands. No invasive carcinoma was identified. There was no evidence of metastatic disease in the ipsilateral sentinel lymph nodes. Thus far, only three cases of squamous cell carcinoma in situ of the breast have been reported in one series-none of which showed any evidence of recurrent or metastatic disease at last follow-up. In our case, treated exclusively by surgery, there was no evidence of disease 11 years after diagnosis. PMID- 27279635 TI - miR-375 exhibits a more effective tumor-suppressor function in laryngeal squamous carcinoma cells by regulating KLF4 expression compared with simple co transfection of miR-375 and miR-206. AB - MicroRNAs (miRNAs) are reported to be important regulators of cancer-related processes, and function either as oncogenes or as tumor-suppressor genes. It was found that miR-375 was downregulated in samples of laryngeal squamous cell carcinomas (LSCCs) as compared to the level noted in adjacent non-tumor tissues, and it was inversely correlated with T grade, lymph node metastases and clinical tumor stage. Overexpression of miR-375 led to a decreased protein level of Kruppel-like factor 4 (KLF4) and marked suppression of the proliferation and invasion, and induced apoptosis of LSCC cell line Hep-2 using Cell Counting Kit 8, Transwell chamber and cell cycle assays. In addition, we examined the influence of the upregulation of miR-206 alone and upregulation of both miR-375 and miR-206 on the expression of KLF4 and Hep-2 cell behavior. The results showed that compared with the function of miR-375 in tumor suppression by regulating KLF4, co-transfection of miR-375 and miR-206 exhibited a less effective inhibitory effect not only on tumor cell proliferation and invasion, but also on tumor cell apoptosis. Taken together, miR-375 is possibly a tumor suppressor in LSCC by regulating KLF4. In addition, simple overexpression of several miRNAs did not entail higher efficacy than a single miRNA, similar to co-transfecions of miR 375 and miR-206. PMID- 27279636 TI - Levels of Occupational Exposure to Solar Ultraviolet Radiation in Vancouver, Canada. AB - INTRODUCTION: Outdoor workers are at high risk of exposure to solar ultraviolet radiation (UVR), a known human carcinogen. In Canada, no objective measures of UVR exposure are available for occupational settings. METHODS: The Outdoor Workers Project collected UVR exposure data among outdoor workers in Vancouver, Canada during the summer of 2013. Objective measures of exposure were taken for one week using calibrated electronic UVR dosimeters. Additional data was collected from workers on skin cancer risk factors, family history of skin cancer, and job type; as well as meteorological data for sampling days. Marginal models were constructed to examine the worker, job and meteorological determinants of UVR exposure levels, as measured in standard erythemal dose (SED). RESULTS: Seventy-eight workers were recruited, of which 73 had at least 1 day of measured UVR exposure for this analysis. Participants were mostly male, young and Caucasian. Mean exposure (corrected for repeated measures) was 1.08 SED. Exposure measures were highly variable even in the same workplace, ranging from 0.01 SED to 19.2 SED. Younger age, working in land-based construction, and sunnier weather forecasts led to higher levels of UVR exposure. CONCLUSIONS: Exposure levels capable of causing sunburn were common in this study of outdoor workers, in a location not typically associated with high sun exposure. PMID- 27279637 TI - Identification of 2 Novel Polymorphisms and rs3138521 in 5' Untranslated Region of SERPINC1 Gene in North Indian Population With Deep Vein Thrombosis. AB - Antithrombin III (AT) is the most important endogenous anticoagulant, and genetic variability in SERPINC1, gene encoding AT, is low. Mutations leading to AT deficiency and increased thrombotic risk are well known; however, only 2 studies have reported mutations in regulatory region of SERPINC1 gene till date. Aim of the present study was to identify genetic variations in SERPINC1 5' untranslated region (UTR) in Indian patients with deep vein thrombosis (DVT) having AT deficiency. DNA sequencing was used to identify underlying genetic defects in SERPINC1 regulatory region. In silico tools TFBIND and PROMO were used to identify transcription factor binding sites in the promoter region. We have identified 2 novel polymorphisms, g.25G>A and g.-1A>T, and 2 known g.67G>A and rs3138521 5' UTR polymorphisms in SERPINC1 regulatory region in Indian patients with DVT for the first time. In present study, allele frequencies of rs3138521 (S: 0.37 and F: 0.63) were similar to that reported in Western population and were not associated with low plasma AT levels ( P value .5). This is the first report of regulatory region polymorphisms in SERPINC1 gene in Indian population. Our results strongly suggest that similar studies should be included when ever no mutation is detected in protein-coding region of AT gene. PMID- 27279638 TI - Simultaneous determination of five common additives in insulating mineral oils by high-performance liquid chromatography with ultraviolet and coulometric detection. AB - Dielectric mineral oils are used to impregnate power transformers and large electrical apparatus, acting as both liquid insulation and heat dissipation media. Antioxidants and passivators are frequently added to mineral oils to enhance oxidation stability and reduce the electrostatic charging tendency, respectively. Since existing standard test methods only allow analysis of individual additives, new approaches are needed for the detection of mixtures. For the first time we investigate and discuss the performance of analytical methods, which require or do not require extraction as sample pretreatment, for the simultaneous reversed-phase high-performance liquid chromatography determination of passivators (benzotriazole, Irgamet((r)) 39) and antioxidants (N phenyl-1-naphtylamine, 2,6-di-tert-butylphenol, 2,6-di-tert-butyl-p-cresol), chosen for their presence in marketed oils. Quick easy, cheap, effective, rugged and safe and solid phase extractions were evaluated as sample pretreatments. Direct sample-injection was also studied. Ultraviolet spectrophotometry and direct-current coulometry detection were explored. As less prone to additive concentrations variability, the direct-injection high-performance liquid chromatography with ultraviolet and coulometric detection method was validated through comparison with Standard Method IEC 60666 and through an ASTM interlaboratory proficiency test. Obtained detection limits are (mg kg(-1) ): benzotriazole (2.8), Irgamet((r)) 39 (13.8), N-phenyl-1-naphtylamine (11.9), 2,6 di-tert-butylphenol (13.1), 2,6-di-tert-butyl-p-cresol (10.2). Simultaneous determination of selected additives was possible both in unused and used oils, with good precision and accuracy. PMID- 27279640 TI - Non-ketotic hyperglycaemia presenting as epilepsia partialis continua. AB - Epilepsia partialis continua is a rare epileptic syndrome observed in patients with brain structural lesions and metabolic disorders. We report a patient with non-ketotic hyperglycaemia presenting as epilepsia partialis continua with reversible focal brain lesions. An 83-year-old woman visited our hospital due to sudden and repetitive left facial twitching lasting for two days. Initial laboratory data revealed serum glucose, osmolality, and sodium levels of 631 mg/dl, 310 mOsm/l, and 130 mEq/l, respectively. EEG was normal. Brain MRI showed low signal changes in the right frontal subcortical area and high signal changes in the surrounding right frontal cortical areas on T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted images. No seizures recurred after correcting blood glucose levels, hydrating the patient, and infusing valproate (900 mg/day). Follow-up MRI, six months later, showed complete resolution of the signal changes in the right frontal cortical and subcortical areas and no clinical seizures. When considering non-ketotic hyperglycaemia with epilepsia partialis continua in an elderly patient, early diagnosis and administration of the appropriate therapy is very important in order to decrease morbidity. PMID- 27279639 TI - Targeted Silencing of S100A8 Gene by miR-24 to Increase Chemotherapy Sensitivity of Endometrial Carcinoma Cells to Paclitaxel. AB - BACKGROUND The objective of this study was to determine whether miR-24 can regulate malignant proliferation and chemotherapy sensitivity of EC cells by targeted silencing of the S100 Calcium Binding Protein A8 (S100A8) gene. MATERIAL AND METHODS The expression of miR-24 in EC tissues was detected by quantitative real-time PCR. The proliferation ability and chemotherapy sensitivity were analyzed by MTT assay. Bioinformatics software was used to predict some potential target genes of miR-24. Luciferase activity assay was used to verify the relationship between target genes and miR-24. S100A8 protein expression was detected by Western blot analysis. RESULTS The low expression of miR-24 in EC tissues compared with normal control tissues suggests miR-24 might play a role in tumorigenesis of EC. EC HEC-1A cells were transfected with miR-24 agonist (agomiR 24) to up-regulate the expression of miR-24. Up-regulation of miR-24 inhibited the cell proliferation and advanced the chemotherapy sensitivity to paclitaxel in HEC-1A cells significantly. We used several types of bioinformatic software to predict that miR-24 could specifically combine with the 3' untranslated region (3'UTR) of the S100A8 gene, and this prediction was verified by Western blot and luciferase activities assay. The regulation effects of miR-24 enhancement on cell proliferation and chemotherapy sensitivity were largely reversed by S100A8 up regulation. CONCLUSIONS miR-24 acts as a tumor-suppressing gene to inhibit malignant proliferation and advance chemotherapy sensitivity to paclitaxel in EC by targeted silencing of the S100A8 gene. PMID- 27279641 TI - Diet and disease: transgressing boundaries between science and society understanding neglected diseases through the lens of cultural studies and anthropology. PMID- 27279642 TI - Impact of genomics on the understanding of microbial evolution and classification: the importance of Darwin's views on classification. AB - Analyses of genome sequences, by some approaches, suggest that the widespread occurrence of horizontal gene transfers (HGTs) in prokaryotes disguises their evolutionary relationships and have led to questioning of the Darwinian model of evolution for prokaryotes. These inferences are critically examined in the light of comparative genome analysis, characteristic synapomorphies, phylogenetic trees and Darwin's views on examining evolutionary relationships. Genome sequences are enabling discovery of numerous molecular markers (synapomorphies) such as conserved signature indels (CSIs) and conserved signature proteins (CSPs), which are distinctive characteristics of different prokaryotic taxa. Based on these molecular markers, exhibiting high degree of specificity and predictive ability, numerous prokaryotic taxa of different ranks, currently identified based on the 16S rRNA gene trees, can now be reliably demarcated in molecular terms. Within all studied groups, multiple CSIs and CSPs have been identified for successive nested clades providing reliable information regarding their hierarchical relationships and these inferences are not affected by HGTs. These results strongly support Darwin's views on evolution and classification and supplement the current phylogenetic framework based on 16S rRNA in important respects. The identified molecular markers provide important means for developing novel diagnostics, therapeutics and for functional studies providing important insights regarding prokaryotic taxa. PMID- 27279643 TI - Multistability and dynamic transitions of intracellular Min protein patterns. AB - Cells owe their internal organization to self-organized protein patterns, which originate and adapt to growth and external stimuli via a process that is as complex as it is little understood. Here, we study the emergence, stability, and state transitions of multistable Min protein oscillation patterns in live Escherichia coli bacteria during growth up to defined large dimensions. De novo formation of patterns from homogenous starting conditions is observed and studied both experimentally and in simulations. A new theoretical approach is developed for probing pattern stability under perturbations. Quantitative experiments and simulations show that, once established, Min oscillations tolerate a large degree of intracellular heterogeneity, allowing distinctly different patterns to persist in different cells with the same geometry. Min patterns maintain their axes for hours in experiments, despite imperfections, expansion, and changes in cell shape during continuous cell growth. Transitions between multistable Min patterns are found to be rare events induced by strong intracellular perturbations. The instances of multistability studied here are the combined outcome of boundary growth and strongly nonlinear kinetics, which are characteristic of the reaction diffusion patterns that pervade biology at many scales. PMID- 27279644 TI - Recurrence and survival rates of inflammatory bowel disease-associated colorectal cancer following postoperative chemotherapy: a comparative study. AB - BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC). Studies have shown tumorigenetic and histomorphological differences between IBD-associated CRC and non-IBD CRC, suggesting differences in tumor behavior and response to treatment. We aimed to compare tumor recurrence and survival rates following postoperative chemotherapy in CRC patients with and without IBD. METHODS: Search of the Cleveland Clinic's CRC database revealed 65 patients who had IBD-associated CRC and received postoperative adjuvant chemotherapy between 1994 and 2010. Twenty-one patients were excluded due to incomplete clinical data. Propensity score-matching based on age, surgery intent, CRC site, tumor grade, American Joint Committee on Cancer (AJCC) stage and T stage was used to match IBD and non-IBD patients (1:4). Competing risk and Cox regression models were used to analyze differences in disease-free survival and overall survival, respectively. RESULTS: Forty-four patients with IBD-associated CRC were matched to 176 patients with non-IBD CRC. Among IBD patients, 29 (66%) had ulcerative colitis, 14 (32%) had Crohn's disease, and one (2%) had indeterminate colitis. Mean IBD diagnosis age was 28.1 +/- 14.5 years, and mean IBD duration at time of CRC treatment was 21.5 +/- 12.6 years. Ten (23%) IBD patients had tumor recurrence compared with 34 (19%) non-IBD patients (P = .074). There was no significant difference in disease-free survival (hazard ratio [HR] = 0.60; 95% CI: 0.35-1.05; P = 0.074) or overall survival (HR = 0.87; 95% CI: 0.54-1.4; P = 0.58) between IBD and non-IBD patients. CONCLUSION: Patients with IBD-associated CRC have comparable rates of tumor recurrence and survival following postoperative chemotherapy as CRC patients without IBD. Prospective studies are needed to confirm these findings and guide therapeutic decisions. PMID- 27279645 TI - Natural Treatments for Fissure in Ano Used by Traditional Persian Scholars, Razi (Rhazes) and Ibn Sina (Avicenna). AB - Most cases of chronic fissure do not respond to medical treatment. Razi and Ibn Sina were 2 of the best-known scientists of ancient Persia. The purpose of this study was to find out new scientific evidence in modern medicine about their recommendations, in order to find certain clues to conduct useful researches in the future. First, treatments of anal fissure mentioned by Razi and Ibn Sina were reviewed. Then, literature search was made in electronic databases including PubMed, Scopus, and Google Scholar. Management of anal fissure according to Razi's and Ibn Sina's practices is done based on 3 interventions: lifestyle modifications, drug treatments, and manual procedures. Almost all remedies suggested by Razi and Ibn Sina have shown their effects on fissure in ano via several mechanisms of action in many in vitro and in vivo studies; Still there is lack of human studies on the subject. PMID- 27279646 TI - Genome-Wide Identification and Analysis of the MYB Transcription Factor Superfamily in Solanum lycopersicum. AB - MYB proteins constitute one of the largest transcription factor families in the plant kingdom, members of which perform a variety of functions in plant biological processes. However, there are only very limited reports on the characterization of MYB transcription factors in tomato (Solanum lycopersicum). In our study, a total of 127 MYB genes have been identified in the tomato genome. A complete overview of these MYB genes is presented, including the phylogeny, gene structures, protein motifs, chromosome locations and expression patterns. The 127 SlMYB proteins could be classified into 18 subgroups based on domain similarity and phylogenetic topology. Phylogenetic analysis of SlMYBs along with MYBs from Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) indicated 14 subfamilies. Conserved motifs outside the MYB domain may reflect their functional conservation. The identified tomato MYB genes were distributed on 12 chromosomes at various densities but mainly in chromosomes 6 and 10 (12.6% and 11.8%, respectively). Genome-wide segmental and tandem duplications were also found, which may contribute to the expansion of SlMYB genes. RNA-sequencing and microarray data revealed tissue-specific and stress-responsive expression patterns of SlMYB genes. The expression profiles of SlMYB genes in response to salicylic acid (SA) and jasmonic acid methyl ester (MeJA) were also investigated by real-time PCR. Moreover, ethylene-responsive element-binding factor-associated amphiphilic repression (EAR) motifs were found in 24 SlMYB proteins. Collectively, our comprehensive analysis of SlMYB genes will facilitate future functional studies of the tomato MYB gene family and probably other Solanaceae plants. PMID- 27279648 TI - Supplemental Security Income Benefits for Mental Disorders. AB - The Supplemental Security Income Program (SSI) provides financial support to low income households with children and youth with severe disabilities. The program included children when it began in the early 1970s. The numbers of children receiving SSI benefits increased substantially in the early 1990s, in part through an expansion of the listings of mental health conditions with which children could become eligible. Over the past 20 years, larger numbers of children have received SSI benefits for mental disorders, and these increases have led to questions from the press and Congress regarding these numbers. Do they indicate more of an increase in mental disorders among SSI children than in the general population? The National Academy of Medicine (NAM; formerly the Institute of Medicine) convened a study panel to examine what is known about mental disorders among the child SSI population and how that compares with evidence about mental disorders in children in general. The NAM report provides detailed information about how SSI works, about the changing numbers of children receiving SSI for mental disorders, and some comparisons with other evidence about rising rates of mental disorders in the general population and especially among children living in poverty. The report indicates that increasing numbers of children with mental disorders in SSI mirror similar increases in the population in general. This article summarizes key evidence from the NAM report and suggests the implications for pediatricians. PMID- 27279647 TI - Comparison of Clinical, Maternal, and Self Pubertal Assessments: Implications for Health Studies. AB - BACKGROUND: Most epidemiologic studies of puberty have only 1 source of pubertal development information (maternal, self or clinical). Interpretation of results across studies requires data on reliability and validity across sources. METHODS: The LEGACY Girls Study, a 5-site prospective study of girls aged 6 to 13 years (n = 1040) collected information on breast and pubic hair development from mothers (for all daughters) and daughters (if >=10 years) according to Tanner stage (T1 5) drawings. At 2 LEGACY sites, girls (n = 282) were also examined in the clinic by trained professionals. We assessed agreement (kappa) and validity (sensitivity and specificity) with the clinical assessment (gold standard) for both the mothers' and daughters' assessment in the subcohort of 282. In the entire cohort, we examined the agreement between mothers and daughters. RESULTS: Compared with clinical assessment, sensitivity of maternal assessment for breast development was 77.2 and specificity was 94.3. In girls aged >=11 years, self-assessment had higher sensitivity and specificity than maternal report. Specificity for both mothers and self, but not sensitivity, was significantly lower for overweight girls. In the overall cohort, maternal and daughter agreement for breast development and pubic hair development (T2+ vs T1) were similar (0.66, [95% confidence interval 0.58-0.75] and 0.69 [95% confidence interval 0.61-0.77], respectively), but declined with age. Mothers were more likely to report a lower Tanner stage for both breast and pubic hair compared with self-assessments. CONCLUSIONS: These differences in validity should be considered in studies measuring pubertal changes longitudinally when they do not have access to clinical assessments. PMID- 27279649 TI - Patient and Parent-Reported Signs and Symptoms for Group A Streptococcal Pharyngitis. AB - BACKGROUND AND OBJECTIVES: Identifying symptomatic patients who are at low risk for group A streptococcal (GAS) pharyngitis could reduce unnecessary visits and antibiotic use. The accuracy with which patients and parents report signs and symptoms of GAS has not been studied. Our objectives were to measure agreement between patient or parent and physician-reported signs and symptoms of GAS and to evaluate the performance of a modified Centor score, based on patient or parent and physician reports, for identifying patients at low risk for GAS pharyngitis. METHODS: Children 3 to 21 years old presenting to a single tertiary care emergency department between October 2013 and January 2015 were included if they complained of a sore throat and were tested for GAS. Patients or parents and physicians completed surveys assessing signs and symptoms to determine a modified age-adjusted Centor score for GAS. We evaluated the overall agreement and kappa between patient or parent and physician-reported signs and symptoms and compared the performance of the scores based on assessments by patients or parents and physicians and the risk of GAS. RESULTS: Of 320 patients enrolled, 107 (33%) tested GAS positive. Agreement was higher for symptoms (fever [agreement = 82%, kappa = 0.64] and cough [72%, 0.45]) than for signs (exudate [80%, 0.41] and tender cervical nodes [73%, 0.18]). Agreement was highest when no signs and symptoms contained in the Centor score were present (94%, kappa = 0.61). The proportion of patients testing GAS positive rose as the modified Centor score increased. CONCLUSIONS: For identifying GAS pharyngitis, patients or parents and physicians showed moderate to substantial agreement for 3 of 4 key pharyngitis signs and symptoms. PMID- 27279651 TI - Interdomain regulation of the ATPase activity of the ABC transporter haemolysin B from Escherichia coli. AB - Type 1 secretion systems (T1SS) transport a wide range of substrates across both membranes of Gram-negative bacteria and are composed of an outer membrane protein, a membrane fusion protein and an ABC (ATP-binding cassette) transporter. The ABC transporter HlyB (haemolysin B) is part of a T1SS catalysing the export of the toxin HlyA in E. coli HlyB consists of the canonical transmembrane and nucleotide-binding domains. Additionally, HlyB contains an N-terminal CLD (C39 peptidase-like domain) that interacts with the transport substrate, but its functional relevance is still not precisely defined. In the present paper, we describe the purification and biochemical characterization of detergent solubilized HlyB in the presence of its transport substrate. Our results exhibit a positive co-operativity in ATP hydrolysis. We characterized further the influence of the CLD on kinetic parameters by using an HlyB variant lacking the CLD (HlyB?CLD). The biochemical parameters of HlyB?CLD revealed an increased basal maximum velocity but no change in substrate-binding affinity in comparison with full-length HlyB. We also assigned a distinct interaction of the CLD and a transport substrate (HlyA1), leading to an inhibition of HlyB hydrolytic activity at low HlyA1 concentrations. At higher HlyA1 concentrations, we observed a stimulation of the hydrolytic activities of both HlyB and HlyB?CLD, which was completely independent of the interaction of HlyA1 with the CLD. Notably, all observed effects on ATPase activity, which were also analysed in detail by mass spectrometry, were independent of the HlyA1 secretion signal. These results assign an interdomain regulatory role for the CLD modulating the hydrolytic activity of HlyB. PMID- 27279654 TI - High spatial resolution imaging of SO and H2CO in AB Auriga: The first SO image in a transitional disk. AB - CONTEXT: Transitional disks are structures of dust and gas around young stars with large inner cavities in which planet formation may occur. Lopsided dust distributions are observed in the dust continuum emission at millimeter wavelengths. These asymmetrical structures can be explained as being the result of an enhanced gas density vortex where the dust is trapped, potentially promoting the rapid growth to the planetesimal scale. AIMS: AB Aur hosts a transitional disk with a clear horseshoe morphology which strongly suggests the presence of a dust trap. Our goal is to investigate its formation and the possible effects on the gas chemistry. METHODS: We used the NOEMA (NOrthern Extended Millimeter Array) interferometer to image the 1mm continuum dust emission and the 13CO J=2 ->1, C18OJ=2 ->1, SO J=56 ->45, and H2CO J=303 ->202 rotational lines. RESULTS: Line integrated intensity ratio images are built to investigate the chemical changes within the disk. The I(H2CO J=303 ->202)/I(C18O J=2->1) ratio is fairly constant along the disk with values of ~0.15+/-0.05. On the contrary, the I(SO J=56 ->45)/I(C18O J=2 ->1) and I(SO J=56 ->45)/I(H2CO J=303 ->202) ratios present a clear northeast-southwest gradient (a factor of 3 6) with the minimum towards the dust trap. This gradient cannot be explained by a local change in the excitation conditions but by a decrease in the SO abundance. Gas densities up to ~109 cm-3 are expected in the disk midplane and two-three times larger in the high pressure vortex. We have used a single point (n,T) chemical model to investigate the lifetime of gaseous CO, H2CO, and SO in the dust trap. Our model shows that for densities >107 cm-3, the SO molecules are depleted (directly frozen, or converted into SO2 and then frozen out) in less than 0.1 Myr. The lower SO abundance towards the dust trap could indicate that a larger fraction of the gas is in a high density environment. CONCLUSIONS: Gas dynamics, grain growth and gas chemistry are coupled in the planet formation process. We detect a chemical signature of the presence of a dust trap in a transitional disk. Because of the strong dependence of SO abundance on the gas density, the sulfur chemistry can be used as a chemical diagnostic to detect the birthsites of future planets. However, the large uncertainties inherent to chemical models and the limited knowledge of the disk's physical structure and initial conditions are important drawbacks. PMID- 27279653 TI - The effect of subarachnoid erythrocyte lysate on brain injury: a preliminary study. AB - Abundant erythrocytes remain and lyse partially in the subarachnoid space after severe subarachnoid haemorrhage (SAH). But the effect of subarachnoid erythrocyte lysate on brain injury is still not completely clear. In this study, autologous erythrocytes (the non-lysate group) and their lysate (the lysate group) were injected separately into the cistern magna of rabbits to induce a model of experimental SAH, although the control group received isotonic sodium chloride solution instead of erythrocyte solution. Results showed that vasospasm of the basilar artery was observed at 72 h after experimental SAH, but there was no significant difference between the non-lysate group and the lysate group. Brain injury was more severe in the lysate group than in the non-lysate group. Meanwhile, the levels of peroxiredoxin 2 (Prx2), IL-6 and TNF-alpha in brain cortex and in CSF were significantly higher in the lysate group than those in the non-lysate group. These results demonstrated that brain injury was more likely to be caused by erythrocyte lysate than by intact erythrocytes in subarachnoid space, and inflammation response positively correlated with Prx2 expression might be involved in mechanism of brain injury after SAH. PMID- 27279655 TI - Reactivity of OH and CH3OH Between 22 and 64 K: Modelling the Gas Phase Production of CH3O in Barnard 1B. AB - In the last years, ultra-low temperature chemical kinetic experiments have demonstrated that some gas-phase reactions are much faster than previously thought. One example is the reaction between OH and CH3OH, which has been recently found to be accelerated at low temperatures yielding CH3O as main product. This finding opened the question of whether the CH3O observed in the dense core Barnard 1b could be formed by the gas-phase reaction of CH3OH and OH. Several chemical models including this reaction and grain-surface processes have been developed to explain the observed abundance of CH3O with little success. Here we report for the first time rate coefficients for the gas-phase reaction of OH and CH3OH down to a temperature of 22 K, very close to those in cold interstellar clouds. Two independent experimental set-ups based on the supersonic gas expansion technique coupled to the pulsed laser photolysis-laser induced fluorescence technique were used to determine rate coefficients in the temperature range 22-64 K. The temperature dependence obtained in this work can be expressed as k(22-64 K) = (3.6 +/- 0.1) * 10-12(T/300 K)-(1.0+/-0.2) cm3 molecule-1 s-1. Implementing this expression in a chemical model of a cold dense cloud results in CH3O/CH3OH abundance ratios similar or slightly lower than the value of ~ 3 * 10-3 observed in Barnard 1b. This finding confirms that the gas phase reaction between OH and CH3OH is an important contributor to the formation of interstellar CH3O. The role of grain-surface processes in the formation of CH3O, although it cannot be fully neglected, remains controversial. PMID- 27279656 TI - Maximum likelihood estimation for semiparametric transformation models with interval-censored data. AB - Interval censoring arises frequently in clinical, epidemiological, financial and sociological studies, where the event or failure of interest is known only to occur within an interval induced by periodic monitoring. We formulate the effects of potentially time-dependent covariates on the interval-censored failure time through a broad class of semiparametric transformation models that encompasses proportional hazards and proportional odds models. We consider nonparametric maximum likelihood estimation for this class of models with an arbitrary number of monitoring times for each subject. We devise an EM-type algorithm that converges stably, even in the presence of time-dependent covariates, and show that the estimators for the regression parameters are consistent, asymptotically normal, and asymptotically efficient with an easily estimated covariance matrix. Finally, we demonstrate the performance of our procedures through simulation studies and application to an HIV/AIDS study conducted in Thailand. PMID- 27279657 TI - Nonparametric maximum likelihood estimation for the multisample Wicksell corpuscle problem. AB - We study nonparametric maximum likelihood estimation for the distribution of spherical radii using samples containing a mixture of one-dimensional, two dimensional biased and three-dimensional unbiased observations. Since direct maximization of the likelihood function is intractable, we propose an expectation maximization algorithm for implementing the estimator, which handles an indirect measurement problem and a sampling bias problem separately in the E- and M-steps, and circumvents the need to solve an Abel-type integral equation, which creates numerical instability in the one-sample problem. Extensions to ellipsoids are studied and connections to multiplicative censoring are discussed. PMID- 27279658 TI - Regression analysis of networked data. AB - This paper concerns regression methodology for assessing relationships between multi-dimensional response variables and covariates that are correlated within a network. To address analytical challenges associated with the integration of network topology into the regression analysis, we propose a hybrid quadratic inference method that uses both prior and data-driven correlations among network nodes. A Godambe information-based tuning strategy is developed to allocate weights between the prior and data-driven network structures, so the estimator is efficient. The proposed method is conceptually simple and computationally fast, and has appealing large-sample properties. It is evaluated by simulation, and its application is illustrated using neuroimaging data from an association study of the effects of iron deficiency on auditory recognition memory in infants. PMID- 27279652 TI - RANK-RANKL signalling in cancer. AB - Oncogenic events combined with a favourable environment are the two main factors in the oncological process. The tumour microenvironment is composed of a complex, interconnected network of protagonists, including soluble factors such as cytokines, extracellular matrix components, interacting with fibroblasts, endothelial cells, immune cells and various specific cell types depending on the location of the cancer cells (e.g. pulmonary epithelium, osteoblasts). This diversity defines specific "niches" (e.g. vascular, immune, bone niches) involved in tumour growth and the metastatic process. These actors communicate together by direct intercellular communications and/or in an autocrine/paracrine/endocrine manner involving cytokines and growth factors. Among these glycoproteins, RANKL (receptor activator nuclear factor-kappaB ligand) and its receptor RANK (receptor activator nuclear factor), members of the TNF and TNFR superfamilies, have stimulated the interest of the scientific community. RANK is frequently expressed by cancer cells in contrast with RANKL which is frequently detected in the tumour microenvironment and together they participate in every step in cancer development. Their activities are markedly regulated by osteoprotegerin (OPG, a soluble decoy receptor) and its ligands, and by LGR4, a membrane receptor able to bind RANKL. The aim of the present review is to provide an overview of the functional implication of the RANK/RANKL system in cancer development, and to underline the most recent clinical studies. PMID- 27279659 TI - Exact simulation of max-stable processes. AB - Max-stable processes play an important role as models for spatial extreme events. Their complex structure as the pointwise maximum over an infinite number of random functions makes their simulation difficult. Algorithms based on finite approximations are often inexact and computationally inefficient. We present a new algorithm for exact simulation of a max-stable process at a finite number of locations. It relies on the idea of simulating only the extremal functions, that is, those functions in the construction of a max-stable process that effectively contribute to the pointwise maximum. We further generalize the algorithm by Dieker & Mikosch (2015) for Brown-Resnick processes and use it for exact simulation via the spectral measure. We study the complexity of both algorithms, prove that our new approach via extremal functions is always more efficient, and provide closed-form expressions for their implementation that cover most popular models for max-stable processes and multivariate extreme value distributions. For simulation on dense grids, an adaptive design of the extremal function algorithm is proposed. PMID- 27279660 TI - Data augmentation for models based on rejection sampling. AB - We present a data augmentation scheme to perform Markov chain Monte Carlo inference for models where data generation involves a rejection sampling algorithm. Our idea is a simple scheme to instantiate the rejected proposals preceding each data point. The resulting joint probability over observed and rejected variables can be much simpler than the marginal distribution over the observed variables, which often involves intractable integrals. We consider three problems: modelling flow-cytometry measurements subject to truncation; the Bayesian analysis of the matrix Langevin distribution on the Stiefel manifold; and Bayesian inference for a nonparametric Gaussian process density model. The latter two are instances of doubly-intractable Markov chain Monte Carlo problems, where evaluating the likelihood is intractable. Our experiments demonstrate superior performance over state-of-the-art sampling algorithms for such problems. PMID- 27279661 TI - Exponential tilting in Bayesian asymptotics. AB - We use exponential tilting to obtain versions of asymptotic formulae for Bayesian computation that do not involve conditional maxima of the likelihood function, yielding a more stable computational procedure and significantly reducing computational time. In particular we present an alternative version of the Laplace approximation for a marginal posterior density. Implementation of the asymptotic formulae and a modified signed root based importance sampler are illustrated with an example. PMID- 27279662 TI - Partial least squares for dependent data. AB - We consider the partial least squares algorithm for dependent data and study the consequences of ignoring the dependence both theoretically and numerically. Ignoring nonstationary dependence structures can lead to inconsistent estimation, but a simple modification yields consistent estimation. A protein dynamics example illustrates the superior predictive power of the proposed method. PMID- 27279650 TI - Vagal Afferent Innervation of the Airways in Health and Disease. AB - Vagal sensory neurons constitute the major afferent supply to the airways and lungs. Subsets of afferents are defined by their embryological origin, molecular profile, neurochemistry, functionality, and anatomical organization, and collectively these nerves are essential for the regulation of respiratory physiology and pulmonary defense through local responses and centrally mediated neural pathways. Mechanical and chemical activation of airway afferents depends on a myriad of ionic and receptor-mediated signaling, much of which has yet to be fully explored. Alterations in the sensitivity and neurochemical phenotype of vagal afferent nerves and/or the neural pathways that they innervate occur in a wide variety of pulmonary diseases, and as such, understanding the mechanisms of vagal sensory function and dysfunction may reveal novel therapeutic targets. In this comprehensive review we discuss historical and state-of-the-art concepts in airway sensory neurobiology and explore mechanisms underlying how vagal sensory pathways become dysfunctional in pathological conditions. PMID- 27279663 TI - Skew-normal antedependence models for skewed longitudinal data. AB - Antedependence models, also known as transition models, have proven to be useful for longitudinal data exhibiting serial correlation, especially when the variances and/or same-lag correlations are time-varying. Statistical inference procedures associated with normal antedependence models are well-developed and have many nice properties, but they are not appropriate for longitudinal data that exhibit considerable skewness. We propose two direct extensions of normal antedependence models to skew-normal antedependence models. The first is obtained by imposing antedependence on a multivariate skew-normal distribution, and the second is a sequential autoregressive model with skew-normal innovations. For both models, necessary and sufficient conditions for [Formula: see text]th-order antedependence are established, and likelihood-based estimation and testing procedures for models satisfying those conditions are developed. The procedures are applied to simulated data and to real data from a study of cattle growth. PMID- 27279664 TI - A pairwise interaction model for multivariate functional and longitudinal data. AB - Functional data vectors consisting of samples of multivariate data where each component is a random function are encountered increasingly often but have not yet been comprehensively investigated. We introduce a simple pairwise interaction model that leads to an interpretable and straightforward decomposition of multivariate functional data and of their variation into component-specific processes and pairwise interaction processes. The latter quantify the degree of pairwise interactions between the components of the functional data vectors, while the component-specific processes reflect the functional variation of a particular functional vector component that cannot be explained by the other components. Thus the proposed model provides an extension of the usual notion of a covariance or correlation matrix for multivariate vector data to functional data vectors and generates an interpretable functional interaction map. The decomposition provided by the model can also serve as a basis for subsequent analysis, such as study of the network structure of functional data vectors. The decomposition of the total variance into componentwise and interaction contributions can be quantified by an [Formula: see text]-like decomposition. We provide consistency results for the proposed methods and illustrate the model by applying it to sparsely sampled longitudinal data from the Baltimore Longitudinal Study of Aging, examining the relationships between body mass index and blood fats. PMID- 27279665 TI - On exchangeable multinomial distributions. AB - We derive an expression for the joint distribution of exchangeable multinomial random variables, which generalizes the multinomial distribution based on independent trials while retaining some of its important properties. Unlike de Finneti's representation theorem for a binary sequence, the exchangeable multinomial distribution derived here does not require that the finite set of random variables under consideration be a subset of an infinite sequence. Using expressions for higher moments and correlations, we show that the covariance matrix for exchangeable multinomial data has a different form from that usually assumed in the literature, and we analyse data from developmental toxicology studies. The proposed analyses have been implemented in R and are available on CRAN in the CorrBin package. PMID- 27279666 TI - A pairwise likelihood-based approach for changepoint detection in multivariate time series models. AB - This paper develops a composite likelihood-based approach for multiple changepoint estimation in multivariate time series. We derive a criterion based on pairwise likelihood and minimum description length for estimating the number and locations of changepoints and for performing model selection in each segment. The number and locations of the changepoints can be consistently estimated under mild conditions and the computation can be conducted efficiently with a pruned dynamic programming algorithm. Simulation studies and real data examples demonstrate the statistical and computational efficiency of the proposed method. PMID- 27279667 TI - Nonparametric identification and maximum likelihood estimation for hidden Markov models. AB - Nonparametric identification and maximum likelihood estimation for finite-state hidden Markov models are investigated. We obtain identification of the parameters as well as the order of the Markov chain if the transition probability matrices have full-rank and are ergodic, and if the state-dependent distributions are all distinct, but not necessarily linearly independent. Based on this identification result, we develop a nonparametric maximum likelihood estimation theory. First, we show that the asymptotic contrast, the Kullback-Leibler divergence of the hidden Markov model, also identifies the true parameter vector nonparametrically. Second, for classes of state-dependent densities which are arbitrary mixtures of a parametric family, we establish the consistency of the nonparametric maximum likelihood estimator. Here, identification of the mixing distributions need not be assumed. Numerical properties of the estimates and of nonparametric goodness of fit tests are investigated in a simulation study. PMID- 27279668 TI - Quantile-based classifiers. AB - Classification with small samples of high-dimensional data is important in many application areas. Quantile classifiers are distance-based classifiers that require a single parameter, regardless of the dimension, and classify observations according to a sum of weighted componentwise distances of the components of an observation to the within-class quantiles. An optimal percentage for the quantiles can be chosen by minimizing the misclassification error in the training sample. It is shown that this choice is consistent for the classification rule with the asymptotically optimal quantile and that under some assumptions, as the number of variables goes to infinity, the probability of correct classification converges to unity. The effect of skewness of the distributions of the predictor variables is discussed. The optimal quantile classifier gives low misclassification rates in a comprehensive simulation study and in a real-data application. PMID- 27279669 TI - Modelling complex survey data with population level information: an empirical likelihood approach. AB - Survey data are often collected with unequal probabilities from a stratified population. In many modelling situations, the parameter of interest is a subset of a set of parameters, with the others treated as nuisance parameters. We show that in this situation the empirical likelihood ratio statistic follows a chi squared distribution asymptotically, under stratified single and multi-stage unequal probability sampling, with negligible sampling fractions. Simulation studies show that the empirical likelihood confidence interval may achieve better coverages and has more balanced tail error rates than standard approaches involving variance estimation, linearization or resampling. PMID- 27279670 TI - Calibrated propensity score method for survey nonresponse in cluster sampling. AB - Weighting adjustment is commonly used in survey sampling to correct for unit nonresponse. In cluster sampling, the missingness indicators are often correlated within clusters and the response mechanism is subject to cluster-specific nonignorable missingness. Based on a parametric working model for the response mechanism that incorporates cluster-specific nonignorable missingness, we propose a method of weighting adjustment. We provide a consistent estimator of the mean or totals in cases where the study variable follows a generalized linear mixed effects model. The proposed method is robust in the sense that the consistency of the estimator does not require correct specification of the functional forms of the response and outcome models. A consistent variance estimator based on Taylor linearization is also proposed. Numerical results, including a simulation and a real-data application, are presented. PMID- 27279671 TI - On varieties of doubly robust estimators under missingness not at random with a shadow variable. AB - Suppose we are interested in the mean of an outcome variable missing not at random. Suppose however that one has available a fully observed shadow variable, which is associated with the outcome but independent of the missingness process conditional on covariates and the possibly unobserved outcome. Such a variable may be a proxy or a mismeasured version of the outcome and is available for all individuals. We have previously established necessary and sufficient conditions for identification of the full data law in such a setting, and have described semiparametric estimators including a doubly robust estimator of the outcome mean. Here, we propose two alternative estimators, which may be viewed as extensions of analogous methods under missingness at random, but enjoy different properties. We assess the correctness of the required working models via straightforward goodness-of-fit tests. PMID- 27279672 TI - Sharp sensitivity bounds for mediation under unmeasured mediator-outcome confounding. AB - It is often of interest to decompose the total effect of an exposure into a component that acts on the outcome through some mediator and a component that acts independently through other pathways. Said another way, we are interested in the direct and indirect effects of the exposure on the outcome. Even if the exposure is randomly assigned, it is often infeasible to randomize the mediator, leaving the mediator-outcome confounding not fully controlled. We develop a sensitivity analysis technique that can bound the direct and indirect effects without parametric assumptions about the unmeasured mediator-outcome confounding. PMID- 27279673 TI - Adsorption and Coupling of 4-aminophenol on Pt(111) surfaces. AB - We have deposited 4-aminophenol on Pt(111) surfaces in ultra-high vacuum and studied the strength of its adsorption through a combination of STM, LEED, XPS and ab initio calculations. Although an ordered (2?3*2?3)R30 degrees phase appears, we have observed that molecule-substrate interaction dominates the adsorption geometry and properties of the system. At RT the high catalytic activity of Pt induces aminophenol to lose the H atom from the hydroxyl group, and a proportion of the molecules lose the complete hydroxyl group. After annealing above 420K, all deposited aminophenol molecules have lost the OH moiety and some hydrogen atoms from the amino groups. At this temperature, short single molecule oligomer chains can be observed. These chains are the product of a new reaction that proceeds via the coupling of radical species that is favoured by surface diffusion. PMID- 27279674 TI - The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016 Statement. AB - We developed a reporting guideline to provide authors with guidance about what should be reported when writing a paper for publication in a scientific journal using a particular type of research design: the single-case experimental design. This report describes the methods used to develop the Single-Case Reporting guideline In BEhavioural interventions (SCRIBE) 2016. As a result of 2 online surveys and a 2-day meeting of experts, the SCRIBE 2016 checklist was developed, which is a set of 26 items that authors need to address when writing about single case research. This article complements the more detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016) that provides a rationale for each of the items and examples of adequate reporting from the literature. Both these resources will assist authors to prepare reports of single-case research with clarity, completeness, accuracy, and transparency. They will also provide journal reviewers and editors with a practical checklist against which such reports may be critically evaluated. We recommend that the SCRIBE 2016 is used by authors preparing manuscripts describing single-case research for publication, as well as journal reviewers and editors who are evaluating such manuscripts. PMID- 27279675 TI - Discriminatory power of common genetic variants in personalized breast cancer diagnosis. AB - Technology advances in genome-wide association studies (GWAS) has engendered optimism that we have entered a new age of precision medicine, in which the risk of breast cancer can be predicted on the basis of a person's genetic variants. The goal of this study is to evaluate the discriminatory power of common genetic variants in breast cancer risk estimation. We conducted a retrospective case control study drawing from an existing personalized medicine data repository. We collected variables that predict breast cancer risk: 153 high-frequency/low penetrance genetic variants, reflecting the state-of-the-art GWAS on breast cancer, mammography descriptors and BI-RADS assessment categories in the Breast Imaging Reporting and Data System (BI-RADS) lexicon. We trained and tested naive Bayes models by using these predictive variables. We generated ROC curves and used the area under the ROC curve (AUC) to quantify predictive performance. We found that genetic variants achieved comparable predictive performance to BI-RADS assessment categories in terms of AUC (0.650 vs. 0.659, p-value = 0.742), but significantly lower predictive performance than the combination of BI-RADS assessment categories and mammography descriptors (0.650 vs. 0.751, p-value < 0.001). A better understanding of relative predictive capability of genetic variants and mammography data may benefit clinicians and patients to make appropriate decisions about breast cancer screening, prevention, and treatment in the era of precision medicine. PMID- 27279676 TI - Single-pixel phase-corrected fiber bundle endomicroscopy with lensless focussing capability. AB - In this paper a novel single-pixel method for coherent imaging through an endoscopic fiber bundle is presented. The use of a single-pixel detector allows greater sensitivity over a wider range of wavelengths, which could have significant applications in endoscopic fluorescence microscopy. First, the principle of lensless focussing at the distal end of a coherent fiber bundle is simulated to examine the impact of pixelation at microscopic scales. Next, an experimental optical correlator system using spatial light modulators (SLMs) is presented. A simple contrast imaging method of characterizing and compensating phase aberrations introduced by fiber bundles is described. Experimental results are then presented showing that our phase compensation method enables characterization of the optical phase profile of individual fiberlets. After applying this correction, early results demonstrating the ability of the system to electronically adjust the focal plane at the distal end of the fiber bundle are presented. The structural similarity index (SSIM) between the simulated image and the experimental focus-adjusted image increases noticeably when the phase correction is applied and the retrieved image is visually recognizable. Strategies to improve image quality are discussed. PMID- 27279677 TI - Assessing the Need for a New Household Panel Study: Health Insurance and Health Care. AB - This paper considers the availability of data for addressing questions related to health insurance and health care and the potential contribution of a new household panel study. The paper begins by outlining some of the major questions related to policy and concludes that survey data on health insurance, access to care, health spending, and overall economic well-being will likely be needed to answer them. The paper considers the strengths and weaknesses of existing sources of survey data for answering these questions. The paper concludes that either a new national panel study, an expansion in the age range of subjects in existing panel studies, or a set of smaller changes to existing panel and cross-sectional surveys, would significantly enhance our understanding of the dynamics of health insurance, access to health care, and economic well-being. PMID- 27279678 TI - Effects of Parent and Child Pre-Intervention Characteristics on Child Skill Acquisition during a School Readiness Intervention. AB - 200 preschool children in Head Start (55% girls; 20% Hispanic, 25% African American, 55% European American; M age = 4.80 years old) participated in a randomized-controlled trial of a home visiting intervention designed to promote their emergent literacy skills (the Research-based Developmentally Informed parent [REDI-P] program). This study explored concurrent changes in levels of parent support and child literacy skills that occurred over the course of the intervention, and examined the impact of pre-intervention parent support and child literacy skills as potential moderators of parent and child outcomes. Cross lagged structural equation models and follow-up analyses indicated that intervention had the strongest impact on child literacy skills when parents were high on support at the pre-intervention assessment. Conversely, the REDI-Parent program promoted the greatest gains in parent support when parents entered the program with low levels. These findings suggest that families may benefit from home visit school readiness interventions in different ways: child skill acquisition may be greatest when parents are initially high in support, whereas parenting may improve most when parents are initially low in support. PMID- 27279679 TI - Digital image classification with the help of artificial neural network by simple histogram. AB - BACKGROUND: Visual image classification is a great challenge to the cytopathologist in routine day-to-day work. Artificial neural network (ANN) may be helpful in this matter. AIMS AND OBJECTIVES: In this study, we have tried to classify digital images of malignant and benign cells in effusion cytology smear with the help of simple histogram data and ANN. MATERIALS AND METHODS: A total of 404 digital images consisting of 168 benign cells and 236 malignant cells were selected for this study. The simple histogram data was extracted from these digital images and an ANN was constructed with the help of Neurointelligence software [Alyuda Neurointelligence 2.2 (577), Cupertino, California, USA]. The network architecture was 6-3-1. The images were classified as training set (281), validation set (63), and test set (60). The on-line backpropagation training algorithm was used for this study. RESULT: A total of 10,000 iterations were done to train the ANN system with the speed of 609.81/s. After the adequate training of this ANN model, the system was able to identify all 34 malignant cell images and 24 out of 26 benign cells. CONCLUSION: The ANN model can be used for the identification of the individual malignant cells with the help of simple histogram data. This study will be helpful in the future to identify malignant cells in unknown situations. PMID- 27279680 TI - Etiological study of lymphadenopathy in HIV-infected patients in a tertiary care hospital. AB - INTRODUCTION: Human immunodeficiency virus (HIV) infection has become a global pandemic. Persistent generalized lymphadenopathy (PGL) is very common manifestation of HIV infection. Moreover, different opportunistic infections such as tuberculosis (TB) and malignancies may present with lymphadenopathy. Mycobacterium avium complex (MAC) infection is most common with cluster of differentiation (CD)4+ count <=50 cells/MUL. Fine-needle aspiration cytology (FNAC) offers a simple and effective modality for obtaining a representative sample of the material from lymph nodes, permitting cytological evaluation and other investigations. AIMS AND OBJECTIVES: The aim of this study is to find out the different etiologies of lymphadenopathy in HIV-infected patients and to establish a possible correlation with CD4+ count. MATERIALS AND METHODS: A total of 100 HIV-infected patients having significant (>1 cm) extrainguinal lymphadenopathy were studied in 1 year at the Department of Pathology by FNAC and the stains used were Leishman-Giemsa, Ziehl-Neelsen (ZN), Papanicoloau, and Gram stains. For tubercular culture, Lowenstein-Jensen (LJ) medium was used. CD4+count was done by flow cytometer. RESULT: The present study revealed four types of cytomorphological variants in lymphadenopathy cases by FNAC, which include: Reactive hyperplasia and caseation necrosis; caseation necrosis and ill-formed granuloma; well-formed granuloma without any necrosis; and non-Hodgkin lymphoma (NHL). The highest acid-fast bacilli (AFB) positivity was among the patients showing caseation necrosis. Tubercular culture in LJ media turned out as a more sensitive method for diagnosis than routine ZN staining. The 2 cases that showed well-formed epithelioid granuloma without any necrosis turned out to be histoplasmosis and cryptococcosis, respectively. In this study, we found 2 cases of NHL. The study also revealed that caseation necrosis and AFB positivity along with opportunistic infections increases with decreased CD4+ count. PMID- 27279681 TI - Utility of immunochemistry in cytology. AB - BACKGROUND: The role played by cytology in primary diagnosis is undeniable. With improved management protocols and targeted therapy, the need for accurate diagnosis has become mandatory. Immunochemistry and molecular techniques are increasingly being used on limited tissue samples. AIMS: This study was conducted to find out the impact of immunocytochemistry (ICC) on cytology material in cytology practice. MATERIALS AND METHODS: Immunochemistry was done on alcohol fixed smears and cell-block preparations. It was done with i6000 BioGenex autostainer using BioGenex reagents. RESULTS: A total of 148 cases occurring over a period of 3 years (September 2010-June 2013) were analyzed. Staining was done on cytology smears in 77 cases and on cell-block sections in 71 cases. ICC helped in diagnosis in 8 cases, confirmed the diagnosis in 26 cases, helped in subtyping in 60 cases, and helped in prognostication in 6 cases. ICC has altered the diagnosis in two cases. It was noncontributory in 43 cases, and the material was inadequate in three cases. CONCLUSION: In 102 cases (69%), ICC proved to be a useful adjunct in the diagnosis and prognostication; hence, its use is recommended in practice to aid in cytology services. PMID- 27279682 TI - Fine needle aspiration cytology of atypical (C3) and suspicious (C4) categories in the breast and its histopathologic correlation. AB - BACKGROUND: In 1996, National Cancer Institute (NCI) proposed five categories for the diagnosis of breast cytology in order to bring a degree of uniformity to the diagnostic reporting. Of these, categories 3 and 4 were sparsely studied. AIMS: The present study was undertaken for the evaluation of the fine needle aspiration cytology (FNAC) categories of C3 and C4 in the breast lump and its histopathological correlation. MATERIALS AND METHODS: In the retrospective study, a total number of 728 FNACs were categorized according to the NCI; of these, 28 cases of category C3 and 65 cases of category C4 were compared with histopathological diagnoses. RESULTS: On histopathological examination of category C3, 18 (64.3%) cases showed benign lesions and 10 (35.7%) cases showed malignancy and among the C4 category, benign lesions found in nine (13.8%) and malignancy found in 56 (86.2%) cases. There was a significant statistical difference between the number of benign and malignant diagnoses for cytological categories of C3 (64.3%) and C4 (86.2%) (P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value of C4 category in the diagnoses of malignancy were 84.8%, 66.7%, 86.2%, and 64.3%, respectively. CONCLUSION: FNAC of the breasts is a simple, cost-effective, accurate, quick, and relatively less painful procedure, and it continues to play an integral part in the management of breast lesions. Our study concluded that there was a statistically significant difference between the number of benign and malignant diagnoses for categories of C3 and C4. PMID- 27279683 TI - A comparative analysis of conventional and SurePath liquid-based cervicovaginal cytology: A study of 140 cases. AB - BACKGROUND: The role of Papanicolaou (Pap) test in cervical cancer screening need not be overemphasized. While most Western countries have adopted the liquid-based cytology (LBC), which is considered superior, many developing countries are still using the conventional Pap smear (CPS) technique. OBJECTIVE: To compare the staining and cytomorphological features on conventional versus liquid-based cervicovaginal smears. MATERIALS AND METHODS: One hundred and forty cervicovaginal smears prepared by the standard conventional and LBC techniques were interpreted as per the Bethesda system of reporting cervicovaginal smears. Twelve parameters were studied, compared, and statistically analyzed. A P value <0.05 was considered to be statistically significant. RESULTS: 129/140 (92%) of CPSs and 130/140 (93%) LBC smears were satisfactory. LBC had a significantly shorter screening time (2.0 +/- 0.08 vs 4.0 +/- 0.65) and better representative material than that of CPS (50% vs 42%). Neutrophils were significantly more in CPS than LBC (96% vs 92%) with a P value <0.05 while hemorrhagic background and red blood cells (RBCs) were more prominent in CPS. LBC showed significant artifactual changes in squamous epithelial cells. Epithelial abnormalities ranging from atypical squamous cells of undetermined significance (ASCUS) to high grade squamous intraepithelial lesion (HSIL) were seen in 3% (4) and 2% (2) of CPSs and LBCs, respectively. Organisms were better picked up in CPS (99% in CPS vs 73% LBC) with a value of P = 0.0001. CONCLUSION: Although a shorter screening time and cleaner background are the major advantages of LBC, CPS is not inferior to LBC. Considering the high cost, rather than the advantages associated with LBC, we feel that CPS is a better option for developing countries. PMID- 27279684 TI - Effusion cytomorphology of small round cell tumors. AB - BACKGROUND: Small round cell tumors (SRCTs) are a group of tumors composed of small, round, and uniform cells with high nuclear/cytoplasmic (N/C) ratios. The appearance of SRCT neoplastic cells in the effusion fluid is very rare. We reported the cytomorphological findings of SRCTs in effusion cytology, and performed statistical and mathematical analyses for a purpose to distinguish SRCTs. MATERIALS AND METHODS: We analyzed the cytologic findings of effusion samples from 40 SRCT cases and measured the lengths of the nuclei, cytoplasms, and the cell cluster areas. The SRCT cases included 14 Ewing sarcoma (EWS)/primitive neuroectodermal tumor cases, 5 synovial sarcoma cases, 6 rhabdomyosarcoma cases, 9 small cell lung carcinoma (SCLC) cases, and 6 diffuse large B-cell lymphoma (DLBL) cases. RESULTS: Morphologically, there were no significant differences in the nuclear and cytoplasmic lengths in cases of EWS, synovial sarcoma, and rhabdomyosarcoma. The cytoplasmic lengths in cases of SCLC and DLBL were smaller than those of EWS, synovial sarcoma, and rhabdomyosarcoma. The nuclear density of the cluster in SCLC was higher than that in other SRCTs, and cases of DLBL showed a lack of anisokaryosis and anisocytosis. CONCLUSION: We believe that it might be possible to diagnose DLBL and SCLC from cytologic analysis of effusion samples but it is very difficult to use this method to distinguish EWS, synovial sarcoma, and rhabdomyosarcoma. Statistical and mathematical analyses indicated that nuclear density and dispersion of nuclear and cytoplasmic sizes are useful adjuncts to conventional cytologic diagnostic criteria, which are acquired from experience. PMID- 27279685 TI - Errors, limitations, and pitfalls in the diagnosis of central and peripheral nervous system lesions in intraoperative cytology and frozen sections. AB - CONTEXT: Intraoperative cytology and frozen section play an important role in the diagnosis of neurosurgical specimens. There are limitations in both these procedures but understanding the errors and pitfalls may help in increasing the diagnostic yield. AIMS: To find the diagnostic accuracy of intraoperative cytology and frozen section for central and peripheral nervous system (PNS) lesions and analyze the errors, pitfalls, and limitations in these procedures. SETTINGS AND DESIGN: Eighty cases were included in this prospective study in a span of 1.5 years. MATERIALS AND METHODS: The crush preparations and the frozen sections were stained with hematoxylin and eosin method. The diagnosis of crush smears and the frozen sections were compared with the diagnosis in the paraffin section, which was considered as the gold standard. STATISTICAL ANALYSES USED: Diagnostic accuracy, sensitivity, and specificity. RESULTS: The diagnostic accuracy of crush smears was 91.25% with a sensitivity of 95.5% and specificity of 100%. In the frozen sections, the overall diagnostic accuracy was 95%, sensitivity was 96.8%, and specificity was 100%. The categories of pitfalls noted in this study were categorization of spindle cell lesions, differentiation of oligodendroglioma from astrocytoma in frozen sections, differentiation of coagulative tumor necrosis of glioblastoma multiforme (GBM) from the caseous necrosis of tuberculosis, grading of gliomas in frozen section, and differentiation of the normal granular cells of the cerebellum from the lymphocytes in cytological smears. CONCLUSIONS: Crush smear and frozen section are complimentary procedures. When both are used together, the diagnostic yield is substantially increased. PMID- 27279686 TI - Diagnostic pitfall in a case of ductal carcinoma-in situ with microinvasion. AB - We report a case of microinvasive carcinoma of the breast cytologically diagnosed as ductal carcinoma - in situ in an 80-year-old lady with a breast lump. Extensive sampling of mastectomy specimen showed ductal carcinoma in situ (DCIS). Many ducts showed stromal reaction - periductal sclerosis and lymphocytic infiltration-features suggestive of microinvasion. However, no definite invasion was noted histologically. Immunohistochemical study highlighted the microinvasive foci. PMID- 27279687 TI - Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto's thyroiditis. AB - Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC) and primary thyroid lymphoma (PTL) are known to coexist and are pathogenetically linked with Hashimoto's thyroiditis (HT). However, HT occurring in association with medullary thyroid carcinoma (MTC) is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC) that was interpreted as "MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node." Total thyroidectomy specimen showed "MTC with coexisting HT." At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hurthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists. PMID- 27279688 TI - Emphasizing the pivotal role of fine-needle aspiration cytology in a case of recurrent malignant chondroid syringoma. AB - Fine-needle aspiration cytology (FNAC) features of malignant chondroid syringoma (MCS) are rarely documented. Here, we report a case of recurrent MCS, highlighting its interesting clinicopathologic features. Initially, we received cytology and histopathology slides (for review) of a 57-year-old woman who had undergone resection for an occipital MCS and later presented with recurrence. On reviewing the slides, cytology was consistent with recurrent MCS. However, tissue sections showed features of a malignant epithelial tumor with comedonecrosis and sebaceous differentiation owing to which a diagnosis of metastatic adenocarcinoma/malignant adnexal tumor was suggested. Due to an ambiguous histology, a repeat FNA was performed to perform immunocytochemistry (ICC) and oil-red O stains, which confirmed the diagnosis of MCS with sebaceous differentiation. Thus, in a situation where histology was inconclusive due to lack of representative sections, FNAC played a major role in resolving the diagnostic dilemma and facilitating an appropriate clinical management. PMID- 27279689 TI - Giant cell tumor of soft tissues of low malignant potential: A rare diagnosis on fine needle aspiration cytology. AB - Primary giant cell tumors of soft tissues (GCT-ST) are extremely rare soft tissue tumors, located in both superficial and deep soft tissues. They resemble osseous giant cell tumors morphologically and immunohistochemically. The tumor exhibits strong positive immunoreactivity for cluster of differentiation 68 (CD68) within multinucleated osteoclast-like giant cells and focal staining of mononuclear cells. Case reports describing the cytohistological features of this entity are very few. We report a case of GCT-ST of low malignant potential diagnosed on fine needle aspiration (FNA) and confirmed on histological and immunohistochemical studies. PMID- 27279690 TI - A rare cytological diagnosis of primary non-Hodgkin lymphoma of the parotid gland. AB - Primary lymphoma of the parotid gland is relatively rare and constitutes about 4 5% of extranodal lymphomas. The majority of them is non-Hodgkin lymphoma (NHL) and is B cell in nature. We report a case of primary diffuse large B-cell lymphoma (DLBCL) of the parotid gland in an elderly male. The case was diagnosed on fine needle aspiration cytology (FNAC) of the right parotid gland as high grade B-cell NHL and confirmed on histopathology as DLBCL. In correlation with the clinicoradiological findings, the case was diagnosed as primary parotid DLBCL. The case highlights the role of FNAC as a timely and useful diagnostic tool. PMID- 27279691 TI - Lingual schwannoma: A cytological diagnosis. PMID- 27279692 TI - Erratum: Epidermal growth factor receptor mutations in nonsmall cell lung carcinoma patients in Kuwait. AB - [This corrects the article on p. 1 in vol. 33, PMID: 27011433.]. PMID- 27279693 TI - In vitro Metabolism of Sodium 9-dehydro-17-hydro-andrographolide-19-yl Sulfate in Rat Liver S9 by Liquid Chromatography-Mass Spectrometry Method. AB - BACKGROUND: Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate (DHAS) is the active ingredient of Xiyanping injection, a traditional Chinese medicine in clinical use. However, there has been no report about the metabolic rate and metabolites of DHAS in vitro. MATERIALS AND METHODS: In this article, DHAS was incubated with rat liver S9, and liquid chromatography/mass spectrometry (LC/MS) was used for the metabolism study. The residual concentrations of substrate were determined by ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for the metabolic rate study of DHAS in liver S9. Metabolites were identified by the (UPLC-TOF-MS(E)) Ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry method. RESULTS: The calibration curves of DHAS were linear over the concentration range from 0.75 MUM to 75.22 MUM with correlation coefficients >0.99. The lower limit of quantification was 0.150 MUM for DHAS. The determination recoveries of DHAS were in the range of 84.9-90.6%. The t1/2 and CLint of DHAS in rat liver S9 were 98.6 +/- 2.1 min and 3.5 +/- 0.1 mL/min/g, respectively. Five metabolites were preliminarily identified based on the high resolution mass spectrum data in comparison with related references. These metabolites were mainly the products of dehydration and hydrogenation of DHAS. CONCLUSION: The present in vitro metabolic study of DHAS provided valuable information about the metabolic rate and potential metabolites of DHAS, which are important for future in vivo metabolism studies of DHAS and the discovery of more active andrographolide derivatives. SUMMARY: In this paper, sodium 9-dehydro-17 hydro-andrographolide-19-yl sulfate (DHAS) metabolism in vitro has been investigated with rat liver S9 using liquid chromatography-mass spectrometry (LC MS). The result of quantitative analysis showed that DHAS had a long t1/2, which indicated its high metabolic stability. Five metabolites of DHAS were identified in the incubation system based on the high resolution mass spectrum data in comparison with related references, particularly dehydrated and hydrogenated products. The results would provide certain references to screen out more active andrographolide derivative for pre-clinically. Abbreviations used: MRM: Multiple reaction monitoring, DHAS: Sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate, IS: Internal standard. PMID- 27279694 TI - Effect of Procyanidin-rich Extract from Natural Cocoa Powder on Cellular Viability, Cell Cycle Progression, and Chemoresistance in Human Epithelial Ovarian Carcinoma Cell Lines. AB - BACKGROUND: Over the last 400 years, cocoa and chocolate have been described as having potential medicinal value, being consumed as a beverage or eaten as food. Concentration-dependant, antiproliferation, and cytotoxic effects of some of their polyphenolic constituents have been demonstrated against various cancers. Such an effect remains to be demonstrated in ovarian cancer. OBJECTIVE: To investigate the effect of cocoa procyanidins against ovarian cancer in vitro using OAW42 and OVCAR3 cell lines. MATERIALS AND METHODS: Cocoa procyanidins were extracted and enriched from non alkalized cocoa powder. The polyphenolic content and antioxidant activity were determined. Effect on cell viability was determined after the treatment with <=1000 MUg/mL cocoa procyanidin-rich extract on OAW42 and OVCAR3 and normal human dermal fibroblasts. Similarly, chemosensitization effect was determined by pretreating cancer cell lines with extract followed by doxorubicin hydrochloride treatment. The effect of treatment on cell cycle and P glycoprotein (P-gp) expression was determined using flow cytometry. RESULTS: The cocoa extract showed high polyphenolic content and antioxidant activity. Treatment with extract caused cytotoxicity and chemosensitization in OAW42 and OVCAR3 cell lines. Normal dermal fibroblasts showed an increase in cell viability post treatment with extract. Treatment with extract affected the cell cycle and an increasing percentage of cells in hypodiploid sub-G1/G0 phase was observed. Treatment of OVCAR3 with the extract caused reduction of P-gp expression. CONCLUSION: Cocoa procyanidins were found to be selectively cytotoxic against epithelial ovarian cancer, interfered with the normal cell cycle and sensitized cells to subsequent chemotherapeutic treatment. Chemosensitization was found to be associated with P-gp reduction in OVCAR3 cells. SUMMARY: Among the naturally occurring flavonoids, procyanidins have been shown to be effective against cancersNon alkalized cocoa powder is one of the richest sources of procyanidinsCocoa procyanidin-rich extract (CPRE) caused cytotoxicity and chemosensitization in ovarian carcinoma cell lines OAW42 and OVCAR3CPRE affected normal cell cycle progressionCPRE also downregulated P-glycoprotein, which mediates chemoresistance in multidrug-resistant OVCAR3 cell line. Abbreviations used: P-gp: P-glycoprotein, CPRE: Cocoa procyanidin rich extract, DMAC: 4 dimethylaminocinnamaldehyde, DPPH: Diphenylpicrylhydrazyl, ABTS: 2,2';-azinobis (3-ethylbenzothiazoline-6-sulfonic acid), PI: Propidium iodide, FITC: Fluorescein isothiocyanate, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, TLC: Thin layer chromatography, HPTLC: High-performance thin layer chromatography. PMID- 27279695 TI - Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid. AB - BACKGROUND: Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders. OBJECTIVE: This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function. MATERIALS AND METHODS: The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined. Brain mitochondria were assayed for MAO type-B (MAO-B) using benzylamine as substrates. Rat brain mitochondrial MAO preparation was used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver Burk plot. RESULTS: MAO activity was inhibited by curcumin and ellagic acid; however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM) were required compared to the known MAO-B inhibitor selegiline. It is observed that the curcumin and ellagic acid inhibit the MAO activity with both the competitive and noncompetitive type of inhibitions. CONCLUSIONS: Curcumin and ellagic acid can be considered a possible source of MAO inhibitor used in the treatment of Parkinson's and other neurological disorders. SUMMARY: Monoamine oxidase (MAO) is involved in a variety of neurological disorders including Parkinson's disease (PD)Curcumin and ellagic acid inhibit the monoamine oxidase activityEllagic acid revealed more potent MAO type-B (MAO-B) inhibitory activity than curcuminKinetic studies of MAO inhibition using different concentrations of curcumin and ellagic acid were plotted as double reciprocal Lineweaver-Burk plotThe mode of inhibition of both compounds toward MAO-B is mixed (competitive and uncompetitive) type of inhibition with both the competitive and noncompetitive type of inhibitions. Abbreviations used: MAO: Monoamine oxidase, IC50: Higher half maximal inhibitory concentrations, PD: Parkinson's disease, LB: Lewy bodies, SNpc: Substantia nigra pars compacta, ROS: Reactive oxygen species, SG: Selegiline, DMC: demethoxycurcumin, BDMC: Bisdemethoxycurcumin. PMID- 27279696 TI - Effect of Withinia Somnifera and Shilajit on Alcohol Addiction in Mice. AB - BACKGROUND: Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. OBJECTIVE: Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential. MATERIALS AND METHODS: Effect of ashwagandha churna and shilajit was measured on ethanol withdrawal anxiety using elevated plus maze. Role of ashwagandha and shilajit on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herbs on corticohippocampal GABA, dopamine, and serotonin levels. RESULTS: Both ashwagandha and shilajit were found to reduce alcohol withdrawal anxiety in a dose-dependent manner. These herbs alone or in combination also decreased ethanol intake and increased water intake significantly after 21 days of chronic administration. Chronic administration of ashwagandha was found to significantly increase GABA and serotonin levels whereas shilajit altered cortico-hippocampal dopamine in mice. CONCLUSION: These central nervous system active herbs alone or in combination reduced both alcohol dependence and withdrawal thus showing promising anti-addictive potential. SUMMARY: Withinia Somnifera alone and in combination with Shilajeet prevented ethanol withdrawal and alcohol addiction Abbreviations used: GABA: Gama aminobutyric acid, CNS: Central Nervous System, CPP:Condition place preference, DA: Dopamine, 5-HT: 5-hydroxytryptamine, NMDA:N-methyl-D-aspartate. PMID- 27279697 TI - Flavonoids Derived from Abelmoschus esculentus Attenuates UV-B Induced Cell Damage in Human Dermal Fibroblasts Through Nrf2-ARE Pathway. AB - BACKGROUND: Ultraviolet-B (UV-B) radiation is a smaller fraction of the total radiation reaching the Earth but leads to extensive damage to the deoxyribonucleic acid (DNA) and other biomolecules through formation of free radicals altering redox homeostasis of the cell. Abelmoschus esculentus (okra) has been known in Ayurveda as antidiabetic, hypolipidemic, demulscent, antispasmodic, diuretic, purgative, etc. OBJECTIVE: The aim of this study is to evaluate the protective effect of flavonoids from A. esculentus against UV-B induced cell damage in human dermal fibroblasts. MATERIALS AND METHODS: UV-B protective activity of ethyl acetate (EA) fraction of okra was studied against UV B-induced cytotoxicity, antioxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2 related factor 2-antioxidant response element (Nrf2-ARE) pathway. RESULTS: Flavonoid-rich EA fraction depicted a significant antioxidant potential also showing presence of rutin. Pretreatment of cells with EA fraction (10-30 MUg/ml) prevented UV-B-induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. CONCLUSION: Our study demonstrated for the 1(st) time that EA fraction of okra may reduce oxidative stress through Nrf2-ARE pathway as well as through endogenous enzymatic antioxidant system. These results suggested that flavonoids from okra may be considered as potential UV-B protective agents and may also be formulated into herbal sunscreen for topical application. SUMMARY: Flavonoid-enriched ethyl acetate (EA) fraction from A. esculentus protected against ultraviolet-B (UV-B)-induced oxidative DNA damageEA fraction prevented UV-B-induced cytotoxicity, depletion of endogenous enzymatic antioxidants, and intracellular reactive oxygen species productionEA fraction could reduce oxidative stress through the Nrf2-ARE PathwayEA fraction was found to be nongenotoxic and prevented apoptotic changes. HIGHLIGHTS: Flavonoids from Abelmoschus esculentus protected from ultraviolet-B-induced damageThey were capable of reducing oxidative stress through Nrf2-ARE PathwayThey are nongenotoxic and do not possess mutagenic potentialFlavonoids from A. esculentus can be studied and explored further for its topical application as sunscreen. Abbreviations used: ABTS: 2,2'-azino-bis-(3-ethylbenzothiazoline -6 sulphonic acid), AO: Acridine orange, ANOVA: Analysis of variance, ARE: Antioxidant response elements, BSA: Bovine serum albumin, CAPE: Caffeic acid phenethyl ester, CAT: Catalase, DCFH-DA: 2',7'-dichlorofluorescein diacetate, DMEM: Dulbecco's modified eagle's medium, DMSO: dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DPBS: Dulbecco's phosphate-buffered saline, DPPH: 2,2 diphenyl-1-picryl hydrazyl, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunosorbent assay, EtBr: Ethidium bromide, FBS: Fetal bovine serum, FE Fraction: Flavonoid-enriched fraction, FRAP: Ferric reducing antioxidant power, GPx: Glutathione peroxidase, GR: Glutathione reductase, GST: Glutathione-S-transferase, GSH: Reduced glutathione, GSSG: Oxidized glutathione, HDF: Human dermal fibroblast adult cells, HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid, HRP: Horseradish peroxidase, HO-1: Heme oxygenase-1, HPTLC: High-performance thin layer chromatography, Keap-1: Kelch-like ECH-associated protein-1, MTT: 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NaCl: sodium chloride, NFDM: nonfat dry milk, Nrf2: Nuclear factor E2-related factor 2, NQO1: NAD (P) H: Quinine oxidoreductase 1, OH: Hydroxyl ions, PBST: Phosphate-buffered saline with 0.1% tween 20, PCR: Polymerase chain reaction, PMSF: Phenylmethanesulfonyl fluoride, Rf: Retention factor, ROS: Reactive oxygen species, rRNA: Ribosomal ribonucleic acid, SDS: Sodium dodecyl sulfate, SOD: Superoxide dismutase, TLC: Thin layer chromatography, TLC-DPPH: Thin layer chromatography-2,2-diphenyl-1 picryl hydrazyl, UV: Ultraviolet, UV-A: Ultraviolet-A, UV-B: Ultraviolet-B, UV-C: Ultraviolet-C, qPCR: Quantitative polymerase chain reaction. PMID- 27279698 TI - Epicatechin Plus Treadmill Exercise are Neuroprotective Against Moderate-stage Amyloid Precursor Protein/Presenilin 1 Mice. AB - BACKGROUND: Epidemiological evidence suggests that exercise and dietary polyphenols are beneficial in reducing Alzheimer's disease (AD) risk. MATERIALS AND METHODS: In the present study, 8 months old amyloid precursor protein/presenilin 1 (APP/PS1) mice (a moderate pathology phase) were given the green tea catechin (-)-epicatechin delivered orally in the drinking water (50 mg/kg daily), along with treadmill exercise for 4 months, in order to investigate whether the combination can ameliorate the cognitive loss and delay the progression of AD in APP/PS1 transgenic (Tg) mice. RESULTS: At termination, untreated-Tg mice showed elevated soluble amyloid-beta (Abeta1-40) and Abeta1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermates. The combined intervention protected against cognitive deficits in the Morris water maze, lowered soluble Abeta1-40 and Abeta1-42 levels in the hippocampus as well as reducing brain oxidative stress. In addition, brain derived neurotrophic factor proteins wee elevated and Akt/GSK-3/cAMP response element-binding protein signaling was activated in the combination group. CONCLUSIONS: Dietary polyphenol plus exercise may exert beneficial effects on brain health and slow the progression of moderate- or mid-stages of AD. SUMMARY: Amyloid precursor protein/presenilin 1 transgenic mice showed elevated soluble amyloid-beta (Abeta1-40) and Abeta1-42 levels and deficits in spatial learning and memory, compared with their wild-type littermatesOral administration of epicatechin, combined with treadmill exercise for 4 months, could protect against cognitive deficits, and lowered soluble Abeta1-40 and Abeta1-42 levels as well as reducing brain oxidative stressBrain-derived neurotrophic factor proteins were elevated, and Akt/GSK-3/cAMP response element binding protein signaling was activated in the combination groupDietary polyphenol plus exercise might exert beneficial effects on brain health and slow the progression of moderate- or mid stages of Alzheimer's disease. Abbreviations used: AD: Alzheimer's disease, Tg: APP/PS1 transgenic, BDNF: Brain-derived neurotrophic factor, Abeta: Amyloid-beta, APP: Amyloid precursor protein, PS1: Presenilin 1, nTg: Wild-type littermates, IACUC: Institutional Animal Care and Use Committee, GSSG: Glutathione oxidized form, GSH: Glutathione reductase, SOD: Superoxide dismutase, CAT: Catalase, LPO: Lipoperoxidation, CREB: cAMP response element binding protein. PMID- 27279699 TI - Protective Effect of High Molecular Weight Protein Sub-fraction of Calotropis procera Latex in Monoarthritic Rats. AB - BACKGROUND: Proteins present in the latex of Calotropis procera have been shown to produce anti-inflammatory effect and to afford protection in various disease models. OBJECTIVES: To determine the efficacy of high molecular weight protein sub-fraction (LPPI) of latex of C. procera in ameliorating joint inflammation and hyperalgesia in a preclinical model of arthritis. MATERIALS AND METHODS: Monoarthritis was induced in rats by intra-articular injection of Freund's complete adjuvant (FCA) and the effect of two doses of LPPI (5 and 25 mg/kg) and diclofenac (5 mg/kg) was evaluated on joint swelling, stair climbing ability, motility, and dorsal flexion pain on day 3. The rats were sacrificed on day 3 to measure tissue levels of reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS). Evaluation of joint histology was also made. RESULTS: Intra-articular injection of FCA produced joint swelling and difficulty in stair climbing ability, motility, and pain on flexion of the joint as revealed by scores obtained for these functional parameters. LPPI produced a dose dependent decrease in joint swelling and improved joint functions. Arthritic rats also revealed altered oxidative homeostasis where joint tissue GSH levels were decreased and TBARS levels were increased as compared to normal rats. The levels of these oxidative stress markers were near normal in arthritic rats treated with LPPI. Moreover, treatment with LPPI also maintained the structural integrity of the joint. The protective effect of LPPI was comparable to the standard anti inflammatory drug, diclofenac. CONCLUSION: The findings of the present study show that LPPI fraction comprising high molecular weight proteins could be used for the alleviation of arthritic symptoms. SUMMARY: High molecular weight protein sub fraction of latex of Calotropis procera (LPPI) reduced joint swelling and hyperalgesia in arthritic ratsLPPI produced a significant improvement in stair climbing ability and motility in arthritic ratsLPPI normalized the levels of oxidative stress markers in the arthritic jointsTreatment with LPPI reduced neutrophil influx and edema in the arthritic joints Abbreviations used: FCA: Freund's complete adjuvant, GSH: Glutathione, TBARS: Thiobarbituric acid reactive substances, TBA: Thiobarbituric acid, MDA: Malondialdehyde, LPPI: Latex protein fraction PI. PMID- 27279700 TI - Pharmacognostic Screening of Piper trichostachyon Fruits and its Comparative Analysis with Piper nigrum Using Chromatographic Techniques. AB - BACKGROUND: Piper trichostachyon is a wild, endemic Piper species from Western Ghats of India. The folklore healers of Belagavi region use this plant, similar to Piper nigrum. AIMS: The present study investigates the comparison between P. nigrum and P. trichostachyon using pharmacognostic parameters. MATERIALS AND METHODS: Pharmacognostic evaluation was carried out in terms of morphological, microscopic characters, and phytochemical analysis using standard methods. Comparative physicochemical analysis between P. trichostachyon and P. nigrum was also carried out through estimation of micro-macro nutrients, high-performance thin layer chromatography (HPTLC) investigation and using piperine as a marker compound for reversed phase-ultra flow liquid chromatographic (RP-UFLC) technique. RESULTS: P. trichostachyon grows in the forests, and the fruits are morphologically similar to P. nigrum fruits, so the name in Kannada "Kaadu Kalu menasu" (wild/forest black pepper). The microscopy revealed the presence of stone cells, starch grains, oil cells and globules, beaker cells, and yellowish brown pigment layer, parenchymatous cells. The presence of alkaloids, oil, and tannins were observed in P. trichostachyon fruits. The HPTLC studies visibly indicated differences among two species with 12 peaks and varied banding pattern. RP-UFLC results showed less amount of piperine in P. trichostachyon (0.05 +/- 0.002 mg/g) than in P. nigrum (16.14 +/- 0.807 mg/g). CONCLUSION: The study reports on pharmacognostic parameters of P. trichostachyon for the 1(st) time and will be useful for the identification and authentication. The comparative HPTLC and RP UFLC studies resolve the differentiation impasse among two species. However, further biological efficacy studies are required to establish its use in traditional medicine. SUMMARY: Piper trichostachyon grows in the forests, and the fruits are morphologically similar to Piper nigrum fruitsThe microscopy of P. trichostachyon revealed the presence of stone cells, starch grains, oil cells and globules, beaker cells and yellowish brown pigment layer, parenchymatous cellsThe high-performance thin layer chromatography studies visibly indicated differences among two species with varied banding patternReversed phase-ultra flow liquid chromatographic results showed less amount of piperine in P. trichostachyon than in P. nigrum. Abbreviation used: HPTLC: High Performance Thin Layer Chromatography, RP-UFLC: Reversed phase-ultra flow liquid chromatographic analysis, DST: Length of line, Maj: Length of large half axis for ellipse RDS - radius for circle, Rf: Retention Factor, TS: Transverse Section, TLC: Thin Layer Chromatography. PMID- 27279701 TI - Reversed Phase High-Performance Liquid Chromatographic Ultra-violet (Photo Diode Array) Quantification of Oleanolic Acid and its Isomer Ursolic Acid for Phytochemical Comparison and Pharmacological Evaluation of Four Leucas Species Used in Ayurveda. AB - CONTENT: Different Leucas species are well known as "Dronpushpi," a well-known herb of Ayurveda, used in the treatment of various ailments. OBJECTIVE: Evaluation of four industrially important Leucas species for their in vitro antidiabetic potential and radical scavenging effect along with high-performance liquid chromatographic quantification of the bioactive triterpenes. MATERIALS AND METHODS: The quantification of triterpenes was carried out on C-18 column with acetonitrile and water (90:10) as the solvent system at a detection wavelength of 210 nm. In vitro antidiabetic activity was evaluated by alpha-amylase inhibition assay based on starch-iodine and 3,5 dinitrosalicylic acid (DNS) method. Antioxidant activity was calculated by five different models, namely total phenolic and total flavonoid content, free radical scavenging activity by 1-1 diphenyl-2-pic-rylhydrazyl (DPPH), ferric-reducing power assay, and the total antioxidant capacity. RESULTS: Maximum concentration of oleanolic acid was found in Leucas cristata, followed by Leucas mollissima, Leucas Aspera, and Leucas biflora. Ursolic acid was highest in L. mollissima and then in L. biflora, L. cristata, and L. aspera, respectively. In in vitro antidiabetic activity, IC50 of L. aspera (1.56 +/- 0.01 mg/ml) and L. mollissima (0.75 +/- 0.005 mg/ml) were found to be highest in DNS and iodine starch assay. IC50 in DPPH assay ranges from 0.6 +/- 0.011 to 1.68 +/- 0.011 mg/ml. Antioxidant capacity follows the order; L. aspera > L. mollissima > L. biflora > L. cristata. CONCLUSION: Promising activities were observed in targeted species, thus L. mollissima, L. biflora, and L. cristata can be used alternatively as a substitute to L. aspera. SUMMARY: Physicochemical parameters are within the limit as per the Ayurvedic Pharmacopoeia of IndiaMaximum concentration of oleanolic acid was found in Leucas cristata; however, ursolic acid was highest in Leucas mollissima In vitro antidiabetic activity of Leucas aspera and L. mollissima was found to be heighest as compared to other species. However, antioxidant capacity is almost similar in targeted species.Promising activities were observed in all the species, thus L. mollissima, Leucas biflora, and L. cristata can be used alternatively as a substitute to L. aspera. PMID- 27279702 TI - DNA Barcoding Identification of Kadsurae Caulis and Spatholobi Caulis Based on Internal Transcribed Spacer 2 Region and Secondary Structure Prediction. AB - BACKGROUND: Kadsurae Caulis and Spatholobi Caulis have very similar Chinese names. Their commodities were hard to distinguish because their stems were very alike after dried and processed. These two herbal drugs were often mixed in clinical use. OBJECTIVE: Authenticity assurance is crucial for quality control of herbal drugs. Therefore, it is essential to establish a method for identifying the two herbs. MATERIALS AND METHODS: In this paper, we used the DNA barcoding technology, based on the internal transcribed spacer 2 (ITS2) regions, to differentiate Kadsurae Caulis and Spatholobi Caulis. RESULTS: The ITS2 of these two herbs were very different. They were successfully differentiated using the DNA barcoding technique. CONCLUSIONS: DNA barcoding was a promising and reliable tool for the identification of medicinal plants. It can be a powerful complementary method for traditional authentication. SUMMARY: The internal transcribed spacer 2 (ITS2) regions between Kadsurae Caulis and Spatholobi Caulis varied considerably, totally 139 variable sitesSample 1 was not Kadsurae Caulis as it labeled, but it should be Spatholobi Caulis in fact based on ITS2 regionThe secondary structure can also separate Kadsurae Caulis and Spatholobi Caulis effectivelyDNA barcoding provided an accurate and strong prove to identify these two herbs. Abbreviations used: CTAB: hexadecyltrimethylammonium bromide, DNA: deoxyribonucleic acid, ITS2:internal transcribed spacer 2, PCR: polymerase chain reaction. PMID- 27279703 TI - Cardioprotective and Antioxidant Influence of Aqueous Extracts from Sesamum indicum Seeds on Oxidative Stress Induced by Cadmium in Wistar Rats. AB - BACKGROUND: Oxidative stress has been implicated in the pathogenesis of several acute and chronic diseases of the heart as a result of indiscriminate exposure to cardiotoxic heavy metals. The study reported here was designed to evaluate the possible ameliorative effect of aqueous extracts from Sesamum indicum (SI) seeds on oxidative stress induced by cadmium (Cd) in Wistar rats. MATERIALS AND METHODS: Daily administration of Cd (200 mg/L Cd as CdCl2) in the animals' main drinking water for 21 days led to oxidative stress. Thereafter, the ameliorative effects were assessed by measuring biochemical parameters such as extent of lipid peroxidation (LPO), lipid profile, and enzymatic and nonenzymatic antioxidants, as well as serum aminotransferase activities. RESULTS: Treatment with SI extract elicited notable reduction in serum total cholesterol, triglyceride, and low density lipoprotein cholesterol levels as well as concomitant increase in high density lipoprotein cholesterol. SI extract also reversed the elevations witnessed in serum aminotransferase activities, LPO level, and ameliorated enzymatic and nonenzymatic antioxidant status in the heart of Cd-exposed rats. CONCLUSION: Thus, SI appears to be an attractive candidate with potential for the novel treatment of cardiotoxicity and management of oxidative stress arising from Cd exposure. SUMMARY: Cadmium (200 mg/L) exposure in drinking water caused pronounced oxidative stress and cardiac tissue damage in animal modelAqueous extract of Sesamum indicum (SI) seeds at a dose of 200 or 400 mg/kg body weight exhibited a significant reversal effect in all biochemical parameters measured such as extent of lipid peroxidation, lipid profile, and enzymatic and nonenzymatic antioxidants, as well as serum aminotransferase activitiesAqueous extract of SI seeds possess antioxidant and cardioprotective potential in a dose dependent manner, thus conferring protection against oxidative stress induced by cadmium. Abbreviation used: SI: Sesamum indicum, Cd: Cadmium, CdCl2: Cadmium chloride, LPO: Lipid peroxidation, TBA: Thiobarbituric acid, ALT: Alanine aminotransferase, AST: Aspartate aminotransferase, ALP: Alkaline phosphatise, TC: Total cholesterol, TG: Triglyceride, HDL-C: Highdensity lipoprotein cholesterol, LDL-C: Low-density lipoprotein cholesterol, SD: Standard deviation, GSH: Glutathione, SOD: Superoxide dismutase, CAT: Catalase, GST: Glutathione-S transferase, GPx: Glutathione peroxidise. PMID- 27279704 TI - Minimization of the Risk of Diabetic Microangiopathy in Rats by Nigella sativa. AB - BACKGROUND: Microangiopathy is a chronic diabetic complication resulting from metabolic derangements, oxidative stress, and increased pro-inflammatory cytokine production. Nigella sativa Linn. is used as an herbal medicine that exerts hypoglycemic, antilipidemic, anti-inflammatory, and antioxidant effects. OBJECTIVE: To examine the effects of N. sativa extract on cutaneous microvascular changes in diabetic rats. MATERIALS AND METHODS: Sprague-Dawley rats were randomly assigned into the following four groups: Untreated and N. sativa-treated normal controls and untreated and N. sativa-treated rats with streptozotocin induced diabetes. A cold-pressed N. sativa extract was then orally administered (1000 mg/kg/day). After 8 weeks of treatment, the glucose, glycosylated hemoglobin (HbA1c), tumor necrosis factor-alpha (TNF-alpha), insulin levels, and lipid profile were determined in cardiac blood. Dermal capillary wall thickness was measured in tail skin sections stained with periodic acid-Schiff. Endothelial apoptosis was morphologically evaluated by hematoxylin and eosin staining. RESULTS: Diabetes significantly reduced the circulating insulin and low-density lipoprotein levels and caused elevations in the glucose, HbA1c, and triglyceride levels, accompanied by a slight increase in total cholesterol levels and no change in the high-density lipoprotein and TNF-alpha levels. Capillary basement membrane thickening and a decreased capillary luminal diameter despite no evidence of endothelial cell apoptosis were also observed. N. sativa treatment of diabetic rats reduced the mean HbA1c concentration by 1.4%, enlarged the capillary lumens, and tended to attenuate dermal capillary basement membrane thickening without affecting the lipid profile or TNF-alpha level. CONCLUSION: Our results indicate that N. sativa may be used to minimize the risk of diabetic microangiopathy, potentially due in part to its glycemic control activity. SUMMARY: Diabetes causes dermal capillary basement membrane thickening and a decreased capillary luminal diameterNigella sativa treatment of diabetic rats enlarged the capillary lumens and tended to attenuate dermal capillary basement membrane thickeningN. sativa treatment of diabetic rats reduced the mean glycosylated hemoglobin concentration by 1.4%, which exceeds the necessary reduction previously described to decrease the risk of diabetic microangiopathy, without affecting the lipid profile or tumor necrosis factor-alpha levelN. sativa improves rat diabetic microangiopathy, potentially due in part to its glycemic control activity. Abbreviations used: H and E: Hematoxylin and eosin, HbA1c: Glycosylated hemoglobin, HDL-C: High-density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, PAS: Periodic acid-Schiff, STZ: Streptozotocin. PMID- 27279705 TI - High Performance Liquid Chromatography-mass Spectrometry Analysis of High Antioxidant Australian Fruits with Antiproliferative Activity Against Cancer Cells. AB - BACKGROUND: High antioxidant capacities have been linked to the treatment and prevention of several cancers. Recent reports have identified several native Australian fruits with high antioxidant capacities. Despite this, several of these species are yet to be tested for anticancer activity. MATERIALS AND METHODS: Solvent extracts prepared from high antioxidant native Australian fruits were analyzed for antioxidant capacity by the di (phenyl)-(2,4,6-trinitrophenyl) iminoazanium free radical scavenging assay. Antiproliferative activities against CaCo2 and HeLa cancer cells were determined by a multicellular tumor spheroid based cell proliferation assay. Toxicity was determined by Artemia franciscana bioassay. RESULTS: Methanolic extracts of all plant species displayed high antioxidant contents (equivalent to approximately 7-16 mg of vitamin C per gram of fruit extracted). Most aqueous extracts also contained relatively high antioxidant capacities. In contrast, the ethyl acetate, chloroform, and hexane extracts of most species (except lemon aspen and bush tomato) had lower antioxidant contents (below 1.5 mg of vitamin C equivalents per gram of plant material extracted). The antioxidant contents correlated with the ability of the extracts to inhibit proliferation of CaCo2 and HeLa cancer cell lines. The high antioxidant methanolic extracts of all species were potent inhibitors of cell proliferation. The methanolic lemon aspen extract was particularly effective, with IC50 values of 480 and 769 MUg/mL against HeLa and CaCo2 cells, respectively. In contrast, the lower antioxidant ethyl acetate and hexane extracts (except the lemon aspen ethyl acetate extract) generally did not inhibit cancer cell proliferation or inhibited to only a minor degree. Indeed, most of the ethyl acetate and hexane extracts induced potent cell proliferation. The native tamarind ethyl acetate extract displayed low-moderate toxicity in the A. franciscana bioassay (LC50 values below 1000 MUg/mL). All other extracts were nontoxic. A total of 145 unique mass signals were detected in the lemon aspen methanolic and aqueous extracts by nonbiased high-performance liquid chromatography-mass spectrometry analysis. Of these, 20 compounds were identified as being of particular interest due to their reported antioxidant and/or anticancer activities. CONCLUSIONS: The lack of toxicity and antiproliferative activity of the high antioxidant plant extracts against HeLa and CaCo2 cancer cell lines indicates their potential in the treatment and prevention of some cancers. SUMMARY: Australian fruit extracts with high antioxidant contents were potent inhibitors of CaCo2 and HeLa carcinoma cell proliferationMethanolic lemon aspen extract was particularly potent, with IC50 values of 480 MUg/mL (HeLa) and 769 MUg/mL (CaCo2)High-performance liquid chromatography-mass spectrometry quadrupole time-of-flight analysis highlighted and putatively identified 20 compounds in the antiproliferative lemon aspen extractsIn contrast, lower antioxidant content extracts stimulated carcinoma cell proliferationAll extracts with antiproliferative activity were nontoxic in the Artemia nauplii assay. Abbreviations used: DPPH: di (phenyl)- (2,4,6-trinitrophenyl) iminoazanium, HPLC: High-performance liquid chromatography, IC50: The concentration required to inhibit by 50%, LC50: The concentration required to achieve 50% mortality, MS: Mass spectrometry. PMID- 27279706 TI - The Anticholinesterase Properties of Plants from the Northeast of Brazil Selected by an Ethnopharmacological Study for Disorders Relating to the Nervous System. AB - BACKGROUND: Various factors may trigger Alzheimer's disease and the cholinergic hypothesis, which is one of the most widely accepted, argues damage to the brain nuclei, may reduce the production of the choline acetyltransferase enzyme, and cause a decline in the synthesis of acetylcholine (ACh). Studies have thus focused on discovering molecules that are capable of inhibiting the action of cholinesterase enzymes that degrade ACh, thereby preventing the evolution of the disease. OBJECTIVE: The aim of the present study is to assess the anticholinesterase properties of extracts of medicinal plants in a semi-arid region of Northeast of Brazil. MATERIALS AND METHODS: The species were selected by way of an ethnobotanical study and were collected if there were some indications that they are related to the nervous system. The plant samples were extracted using hexane, ethyl acetate, and methanol. Anticholinesterase activity in vitro was assessed by way of bioautography in thin layer chromatography and microassays in 96-well plates. RESULTS: Twenty-three species of plant were collected, and 75 extracts were analyzed. The bioautography revealed that 26.7% of the samples showed inhibitory activity against the acetylcholinesterase (AChE) enzyme. After the test for false positives, 8% of the samples were found to inhibit AChE. Thirty samples were analyzed by microassay (500 MUg/mL), on which 86.7% showed moderate to powerful anticholinesterase activity. CONCLUSION: Of the extracts tested, Citrus limonum, Ricinus communis, and Senna occidentalis stand out as was the most promising in terms of anticholinesterase activity and may serve as a guide for the discovery and development of new substances for the treatment of AD. SUMMARY: The bioautography revealed that 26.7% of the samples showed inhibitory activity against the acetylcholinesterase enzymeSamples were analyzed by microassay (500 MUg/mL), upon which 86.7% showed moderate to powerful anticholinesterase activityCitrus limonum, Ricinus communis, and Senna occidentalis stand out as being the most promising in terms of anticholinesterase activityC. limonum, R. communis, and S. occidentalis may serve as a guide for the discovery and development of new substances for the treatment of Alzheimer's disease. Abbreviations used: AChE: Acetilcolinesterase. PMID- 27279707 TI - Intrathecal Injection of Resveratrol Attenuates Burn Injury Pain by Activating Spinal Sirtuin 1. AB - OBJECTIVE: The present study sought to detect spinal sirtuin 1 (SIRT1) and acetylation of histone H3 (Ac-H3) expression in rats with burn injury pain (BIP model). PROCEDURES AND RESULTS: A BIP model was first established. BIP rats showed lower paw withdrawal threshold (PWT) from day 1, which persisted for 21 days following the burn injury. Spinal SIRT1/Ac-H3 expression increased following burn injury. The intrathecal use of resveratrol increased PWT and SIRT1 expression but induced down-regulation of Ac-H3 expression. We first demonstrated that the inhibition of SIRT1 significantly induced mechanical allodynia in naive rats. The preinjection of SIRT1 inhibitor partly antagonized the analgesic effects of resveratrol in BIP rats. CONCLUSION: Inhibition of SIRT1 produces pain facilitation in the naive rats. The expression of spinal SIRT1 increased after burn injury in the BIP model. The activation of spinal SIRT1 might mediate the resveratrol-induced analgesic effects. SUMMARY: Burn injury resulted in pain facilitationResveratrol attenuates pain facilitation induced by burn injuryIntrathecal injection of resveratrol attenuates burn injury pain by increasing spinal sirtuin 1 (SIRT1) expressionInhibition of SIRT1 by selisistat, an SIRT1 inhibitor attenuated analgesic effects of resveratrol Abbreviations used: SIRT1: Sirtuin 1, Ac-H3: Acetylation of histone H3, SD: Sprague-Dawley, EX527: Selisistat, an SIRT1 inhibitor, BIP: Burn injury pain, DMSO: Dimethyl sulfoxide, PWTs: Paw withdrawal thresholds. PMID- 27279708 TI - Evaluation of Xanthine Oxidase Inhibitory Potential and In vivo Hypouricemic Activity of Dimocarpus longan Lour. Extracts. AB - BACKGROUND: Longan is a fruit tree known to contain many phenolic components, which are capable of protecting people from oxidative damage through an anti inflammatory mechanism. It may be also worthwhile to study the effect on lowering uric acid activity. MATERIALS AND METHODS: This study investigates the lowering of uric acid using longan extracts, including flowers, pericarps, seeds, leaves, and twigs, on potassium-oxonate-induced hyperuricemia mice and its inhibitory actions against xanthine oxidase (XO) activities. RESULTS: The findings revealed that ethyl acetate fraction of longan extracts exhibited strong XO-inhibitory activity, and the flower extracts (IC50 = 115.8 MUg/mL) revealed more potent XO inhibitory activity to those of pericarps (118.9 MUg/mL), twigs (125.3 MUg/mL), seeds (262.5 MUg/mL), and leaves (331.1 MUg/mL) in vitro. In addition, different dosages of longan extract (50-100 mg/kg) were administered to hyperuricemic mice. The lowering effect of longan extracts on uric acid at 75 mg/kg markedly reduced plasma uric acid levels in decreasing order: Flowers (80%) > seeds (72%) > pericarps (64%) > twigs (59%) > leaves (41%), compared with allopurinol (89%). Finally, 10 isolated phytochemicals from longan flowers were then examined in vitro. The results indicated that proanthocyanidin A2 and acetonylgeraniin A significantly inhibited XO activity in vitro. This is the first report providing new insights into the urate-reducing effect of phenolic dimer and hydrolyzable tannin, which can be developed to potential hypouricemic agents. SUMMARY: Longan flower extracts possess more potent XO-inhibitory activity than pericarps, twigs, seeds, and leaves in vitroThe lowering effect of longan flowers and seeds extracts markedly reduced plasma uric acid levels as compared to allopurinol in vivoThe extract proanthocyanidin A2 and acetonylgeraniin A were demonstrated potent XO inhibitory activity in vitro Abbreviations used: PO: Potassium-oxonate, XO: xanthine oxidase, HE: n-hexane, EA: ethyl acetate, i.p.: intraperitoneal, PBS: phosphate-buffered saline, AP: allopurinol, PUA: plasma uric acid. PMID- 27279709 TI - Ketosteroid Standardized Cissus quadrangularis L. Extract and its Anabolic Activity: Time to Look Beyond Ketosteroid? AB - BACKGROUND: Cissus quadrangularis (CQ) L. reported to contain 3-ketosteroids and have bone health benefits. AIM: This study aimed at establishing the relationship between the ketosteroid content and anabolic as well as bone health-promoting activities of various Cissus extracts in well-established orchidectomized (ORX) rat model. MATERIALS AND METHODS: Supercritical carbon dioxide, ethyl acetate, and aqueous extracts (AE) of CQ L. were prepared and standardized for ketosteroid content by two methods used in commerce. Moreover, ketosteroid standardized extracts of this plant were evaluated for anabolic activity in rats in well established ORX rat model. RESULTS: The increase in the absolute weight was appreciable in the CQ-AE treated group. Similarly, with respect to bone parameters, a similar trend was seen. The mean bone density, strength, and calcium content were found to be highest in the group treated with CQ-AE compared to groups treated with other extracts. This study reveals for the first time that 3-ketosteroids are not linked to the beneficial activities on bone and highlights the need for extensive characterization of biological active principles from CQ L. CONCLUSION: In light of the above estimation studies, we believe that current standardization of Cissus extraction "3-ketosteroids" is incorrect. We also did not find any report suggesting the presence of androgenic steroids in this plant and hence the characterization based on "3-ketosteroids" is scientifically incorrect. This study highlights the insufficient understanding of biological active principles from CQ L. and underlines the need for extensive bioactivity guided studies. SUMMARY: Cissus quadrangularis (CQ) L. reported to contain 3.ketosteroids and have bone health benefitsWe did not find correlation between ketosteroid content obtained by conventional methods and its biological effectStudies indicate that claims of ketosteroid content need not necessarily correlate to biological effects and hence warrants extensive phytochemical characterization of biological active principles from CQ L. Abbreviations used: CQ: Cissus quadrangularis, ORX: Orchidectomized, AE: Aqueous extract, EE: Ethyl acetate extract, SFE: Supercritical fluid extract. PMID- 27279710 TI - Pyrostegia venusta (Ker Gawl.) Miers Crude Extract and Fractions: Prevention of Dental Biofilm Formation and Immunomodulatory Capacity. AB - BACKGROUND: Caries and periodontal diseases remain as important diseases in the Brazilian population. One important pathogen associated with this situation is Streptococcus mutans and other important factor is this pathogen's ability to adhere firmly to the tooth surface leading to dental biofilm formation and caries development. OBJECTIVES: Determine the antibacterial and other biological activities of P. venusta related to its potential to be used in the treatment of caries and periodontal disease. METHODS: The growth inhibition by P. venusta of Streptococcus mutans, S. mitis, S. oralis and Candida albicans was determined using the broth microdilution method. In addition, the effect of the samples in adherence and reducing production of acids by S. mutans, and germ-tube formation of C. albicans was analysed. The Nitric Oxide (NO) production and cytotoxicity of P. venusta to peripheral blood mononuclear cells (PBMC) and RAW 264.7 Cell Line Murine Macrophage from Blood were assessed. RESULTS: The crude extract (CE) and ethyl-acetate (AF) and n-butanol (BF) fractions showed antibacterial activity. The ethyl-acetate (AF) fraction showed the highest inhibition percentage against the adherence of S. mutans and C. albicans cells without budding, beyond NO production inhibition. There was not any cytotoxicity in the murine macrophages RAW 264.7 cells. CONCLUSION: Our results suggest that P. venusta presents potential to be used as a preliminary source of compounds that can provide helpful activity when used in prophylaxis or treatment of caries or periodontal disease. SUMMARY: Biological activities of Pyrostegia venusta and its potential for use in formulations for the prevention of oral diseases. Abbreviations used: NO: Nitric oxide, PBMC: Peripheral blood mononuclear cells, CE: Crude extract, AF: Ethyl-acetate fraction, BF: n-butanol fraction, HF: Hexane fraction, WF: Water fraction, MIC: Minimum inhibitory concentration, MBC: Minimum bactericidal concentration, ATCC: American Type Culture Collection, CFU: Colony-forming units, BHI: Brain heart infusion, RPMI: Roswell Park Memorial Institute, MOPS: 3-(N morpholino)propanesulfonic acid, DMEM: Dulbecco's modified Eagle's medium, LPS: Lipopolysacharide, MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide, OD: Optical density, AC: Acteoside. PMID- 27279711 TI - Phytochemicals from Tradescantia albiflora Kunth Extracts Reduce Serum Uric Acid Levels in Oxonate-induced Rats. AB - BACKGROUND: Tradescantia albiflora (TA) Kunth (Commelinaceae) has been used for treating gout and hyperuricemia as folklore remedies in Taiwan. Therefore, it is worthwhile to study the effect of TA extracts on lowering uric acid activity. The hypouricemic effects of TA extracts on potassium oxonate (PO)-induced acute hyperuricemia were investigated for the first time. MATERIALS AND METHODS: All treatments at the same volume (1 ml) were orally administered to the abdominal cavity of PO-induced hyperuricemic rats. One milliliter of TA extract in n-hexane (HE), ethyl acetate (EA), n-butanol (BuOH), and water fractions has 0.28, 0.21, 0.28, and 1.03 mg TA, respectively; and the plasma uric acid (PUA) level was measured for a consecutive 4 h after administration. RESULTS: All four fractions' extracts derived from TA were observed to significantly reduce PUA compared with the PO group. The EA-soluble fraction (TA-EA) exhibited the best xanthine oxidase (XO) inhibitory activity. Following column chromatography, 12 phytochemicals were isolated and identified from the EA fraction. The IC50 values of isolated phytochemicals indicated that bracteanolide A (AR11) showed the remarkable XO inhibitory effect (IC50 value of 76.4 MUg/ml). These findings showed that the in vivo hypouricemic effect in hyperuricemic rats was consistent with in vitro XO inhibitory activity, indicating that TA extracts and derived phytochemicals could be potential candidates as hypouricemic agents. SUMMARY: Tradescantia albiflora extracts possess in vivo hypouricemic action in hyperuricemic ratsT. albiflora extracts exhibited strong inhibitory activity against xanthine oxidase (XO)Butenolide may play an important role in XO inhibitionThe extract bracteanolide A was demonstrated potent XO inhibitory activity in vitro. Abbreviations used: TA: Tradescantia albiflora, PO: potassium oxonate, HE: n hexane, EA: ethyl acetate, BuOH: n-butanol, PUA: plasma uric acid, XO: xanthine oxidase, MeOH: methanol, IP: intraperitoneal. PMID- 27279712 TI - Life Span and Motility Effects of Ethanolic Extracts from Sophora moorcroftiana Seeds on Caenorhabditis elegans. AB - BACKGROUND: Sophora moorcroftiana is an endemic shrub species with a great value in folk medicine in Tibet, China. In this study, relatively little is known about whether S. moorcroftiana is beneficial in animals' nervous system and life span or not. MATERIALS AND METHODS: To address this question, under survival normal temperature (25 degrees C), S. moorcroftiana seeds were extracted with 95% ethanol, and Caenorhabditis elegans were exposed to three different extract concentrations (100 mg/L, 200 mg/L, and 400 mg/mL) from S. moorcroftiana seeds. RESULTS: The 95% ethanolic extracts from S. moorcroftiana seeds could increase life span and slow aging-related increase in C. elegans and could not obviously influence the motility of C. elegans. CONCLUSION: Given these results by our experiment for life span and motility with 95% ethanolic extracts from S. moorcroftiana seeds in C. elegans, the question whether S. moorcroftiana acts as an anti-aging substance in vivo arises. SUMMARY: The 95% ethanolic extracts from S. moorcroftiana seeds have no effect on the life span in C. elegans when extract concentrations from S. moorcroftiana seeds <400 mg/LThe 400 mg/L 95% ethanolic extracts from S. moorcroftiana seeds could increase life span in C. elegansThe 95% ethanolic extracts from S. moorcroftiana seeds could not obviously influence the motility in C. elegans. Abbreviation used: S. moorcroftiana: Sophora moorcroftiana; C. elegan: Caenorhabditis elegan; E. coli OP50: Escherichia coli OP50; DMSO: Dimethyl sulfoxide. PMID- 27279713 TI - Chemopreventive Agents from Physalis minima Function as Michael Reaction Acceptors. AB - BACKGROUND: The fruits of some varieties of genus Physalis have been used as delicious fruits and functional food in the Northeast of China. MATERIALS AND METHODS: To reveal the functional material basis, we performed bioactivity-guided phytochemical research and chemopreventive effect assay of the constituents from Physalis minima. RESULTS: It was demonstrated that the ethyl acetate extract of P. minima L. (EEPM) had potential quinone reductase (QR) inducing activity with induction ratio (IR, QR induction activity) value of 1.47 +/- 0.24, and glutathione binding property as potential Michael reaction acceptors (with an alpha, beta-unsaturated ketone moiety). Furthermore, bioactivity-guided phytochemical research led eight compounds (1-8), which were elucidated as 3 isopropyl-5-acetoxycyclohexene-2-one-1 (1), isophysalin B (2), physalin G (3), physalin D (4), physalin I (5), physordinose B (6), stigmasterol-3-O-beta-D glucopyranoside (7) and 5alpha-6beta-dihydroxyphysalin R (8) on the basis of nuclear magnetic resonance spectroscopy analyses and HRESIMS. Then, isophysalin B (2) and physordinose B (6) showed significant QR inducing activity with IR value of 2.80 +/- 0.19 and 2.38 +/- 0.46, respectively. SUMMARY: An ultra-performance liquid chromatographic method with glutathione as the substrate was used to detect the Michael reaction acceptors in extracts of Physalis minima (EPM)We investigated the chemical constituents of EPM guided by biological activity methodIsophysalin B (1) and physordinose B (6) showed strong quinone reductase inducing activity with induction ratio values of 2.80 +/- 0.19 and 2.38 +/- 0.46This study generated useful information for consumers and many encourage researchers to utilize edible fruits from Physalis as a source of phytochemicals Abbreviations used: EPM: Extracts of Physalis minima, EEPM: Ethyl acetate extract of Physalis minima L., GSH: Glutathione, MRAs: Michael reaction acceptors, QR: Quinone reductase. PMID- 27279714 TI - Quercetin Suppresses the Migration and Invasion in Human Colon Cancer Caco-2 Cells Through Regulating Toll-like Receptor 4/Nuclear Factor-kappa B Pathway. AB - OBJECTIVE: The migration and invasion features, which were associated with inflammatory response, acted as vital roles in the development of colon cancer. Quercetin, a bioflavonoid compound, was widely spread in vegetables and fruits. Although quercetin exerts antioxidant and anticancer activities, the molecular signaling pathways in human colon cancer cells remain unclear. Hence, the present study was conducted to investigate the suppression of quercetin on migratory and invasive activity of colon cancer and the underlying mechanism. MATERIALS AND METHODS: The effect of quercetin on cell viability, migration, and invasion of Caco-2 cells was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay, wound-healing assay, and transwell chambers assay, respectively. The protein expressions of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-kappaB) p65, mitochondrial membrane potential-2 (MMP 2), and MMP-9 were detected by Western blot assay. The inflammatory factors, such as tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6), in cell supernatant were detected by enzyme-linked immunosorbent assay. RESULTS: The concentration of quercetin <20 MUM was chosen for further experiments. Quercetin (5 MUM) could remarkably suppress the migratory and invasive capacity of Caco-2 cells. The expressions of metastasis related proteins of MMP-2, MMP-9 were decreased, whereas the expression of E cadherin protein was increased by quercetin in a dose-dependent manner. Interestingly, the anti-TLR4 (2 MUg) antibody or pyrrolidine dithiocarbamate (PDTC; 1 MUM) could affect the inhibition of quercetin on cell migration and invasion, as well as the protein expressions of MMP-2, MMP-9, E-cadherin, TLR4, and NF-kappaB p65. In addition, quercetin could reduce the inflammation factors production of TNF-alpha, Cox-2, and IL-6. CONCLUSION: The findings suggested for the 1(st) time that quercetin might exert its anticolon cancer activity via the TLR4- and/or NF-kappaB-mediated signaling pathway. SUMMARY: Quercetin could remarkably suppress the migratory and invasive capacity of Caco-2 cellsThe expressions of metastasis-related proteins of mitochondrial membrane potential-2 (MMP-2), MMP-9 were decreased, whereas the expression of E-cadherin protein was increased by quercetin in a dose-dependent mannerThe anti-toll-like receptor 4 (TLR4) antibody or pyrrolidine dithiocarbamate affected the inhibition of quercetin on cell migration and invasion, as well as the protein expressions of MMP-2, MMP-9, E-cadherin, TLR4, and nuclear factor-kappa B p65Quercetin could reduce the inflammation factors production of tumor necrosis factors-alpha, cyclooxygenase-2, and interleukin-6. Abbreviations used: MTT: 3-(4,5 dimethylthiazol-2-yl)- 2,5-diphen yltetrazolium bromide, TLR4: Toll-like receptor 4, NF-kappaB: Nuclear factor-kappa B, MMP-2: Mitochondrial membrane potential-2, MMP-9: Mitochondrial membrane potential-9, TNF-alpha: Tumor necrosis factor alpha, Cox-2: Cyclooxygenase-2, IL-6: Interleukin-6, ELISA: Enzyme-linked immunosorbent assay, PDTC: Pyrrolidine dithiocarbamate, ROS: Reactive oxygen species, DMSO: Dimethyl sulfoxide, FBS: Fetal bovine serum, DMEM: Dulbecco modified Eagle medium, OD: Optical density, IPP: Image Pro-plus, PBS: Phosphate buffered saline, SD: Standard deviation, ANOVA: One-way analysis of variance, SPSS: Statistical Package for the Social Sciences, ECM: Extracellular matrix, TLRs: Toll-like receptors, LPS: Lipopolysaccharide. PMID- 27279715 TI - Preparation and Evaluation of Andrographolide Solid Dispersion Vectored by Silicon Dioxide. AB - BACKGROUND: Andrographolide (Andro) is a "natural antibiotic" as well as a typical insoluble drug. The purpose of this study was to investigate the feasibility of commercially available silica (SiO2) as a carrier of solid dispersion to enhance the dissolution of Andro. MATERIALS AND METHODS: The solvent evaporation method was adopted, and a series of process parameters were studied to prepare a solid dispersion. Andro, SiO2, physical mixture, and solid dispersion were characterized with respect to particle size distribution, special surface area, pore volume, and scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction studies. RESULTS: Single factor test suggested the best preparation of solid dispersion was the drug and carrier (SiO2B) ratio of 1:8, with tetrahydrofuran as the solvent, and a recovery temperature of 50 degrees C. Compared to crude drug and mixture, solid dispersion was found to form a unique structure to disperse the drug and displayed superior performance in rapid dissolution. CONCLUSION: The present study signifies the commercially available SiO2 is an excellent but cheap carrier to improve the dissolution of Andro. Our results provide a highly operability approach for improving the dissolution of insoluble natural products and are beneficial for the clinical effects improvement. SUMMARY: The potential of commercially available silica as a carrier for enhancing the insoluble drug dissolution was investigatedFactors affecting the dissolution of solid dispersion were investigatedSolid dispersion formed a unique structure to disperse the drug and release drug rapidlyCommercially available silica is an excellent but cheap carrier to improve the dissolution of Andro. Abbreviation used: Andro: Andrographolide, BCS: Biopharmaceutics Classification System, SDS: Tetrahydrofuran and Sodium dodecyl sulfate, HPLC: High Performance Liquid Chromatography, SEM: Scanning Electron Microscope, BET: Brumauer-Emmett-Teller, FTIR: Fourier Transform Infrared Spectroscopy, XRD: X-ray Diffraction. PMID- 27279716 TI - Total Alkaloids of Sophora alopecuroides Inhibit Growth and Induce Apoptosis in Human Cervical Tumor HeLa Cells In vitro. AB - BACKGROUND: Uygur females of Xinjiang have the higher incidence of cervical tumor in the country. Alkaloids are the major active ingredients in Sophora alopecuroides, and its antitumor effect was recognized by the medical profession. Xinjiang is the main site of S. alopecuroides production in China so these plants are abundant in the region. Studies on the antitumor properties of total alkaloids of S. alopecuroides (TASA) can take full use of the traditional folk medicine in antitumor unique utility. OBJECTIVES: To explore the effects of TASA on proliferation and apoptosis of human cervical tumor HeLa cells in vitro. MATERIALS AND METHODS: TASA was extracted, purified, and each monomer component was analyzed by high-performance liquid chromatography. The effect of TASA at different concentrations on the survival of HeLa cells was determined after 24 h using the Cell Counting Kit-8. In addition, cells were photographed using an inverted microscope to document morphological changes. The effect of TASA on apoptotic rate of HeLa cells was assessed by flow cytometry. RESULTS: Monomers of TASA were found to be sophoridine, matrine, and sophocarpine. On treatment with 8.75 mg/ml of TASA, more than 50% of HeLa cells died, and cell death rate increased further with longer incubation. The apoptotic rates of HeLa cells in the experimental groups were 16.0% and 33.3% at concentrations of 6.25 mg/ml and 12.50 mg/ml, respectively. CONCLUSION: TASA can induce apoptosis in cervical tumor HeLa cells, and it has obvious inhibitory effects on cell growth. SUMMARY: Total alkaloids of Sophora alopecuroides (TASA) exhibits anti-human cervical tumor propertiesMonomer component of TASA was analyzed by high-performance liquid chromatography, and its main effect component are sophoridine, matrine, and sophocarpineTASA inhibits growth and induces apoptosis in HeLa cells. Abbreviations used: TASA: Total alkaloids of S. alopecuroides, CCK-8: Cell Counting Kit-8, FBS: Fetal bovine serum, PBS: Phosphate buffered saline, DMEM: Dulbecco's modified Eagle medium. PMID- 27279717 TI - The Inhibitory Effect of Rhein on Proliferation of High Glucose-induced Mesangial Cell Through Cell Cycle Regulation and Induction of Cell Apoptosis. AB - OBJECTIVES: Increased mesangial cell proliferation and accumulation of extracellular matrix (ECM) are the major pathological features of early-stage diabetic nephropathy. This study was sought to investigate the inhibitory effects of rhein (RH) on high glucose (HG)-cultured mesangial cells. Specially, we focus on the analysis of proliferation rate, cell cycle regulation, apoptosis, and the expression of collagen IV and laminin. MATERIALS AND METHODS: The established rat renal mesangial cell (RMC) line was cultured in medium with different concentrations of glucose (5.6 mM or 25 mM) and RH (40 MUM, 20 MUM, and 10 MUM). Pro-treated cells were collected at 12 h, 24 h, and 48 h for cell proliferation analysis and after 24 h for the experiments of flow cytometry, transmission electron microscope, real-time polymerase chain reaction, and Western blotting. RESULTS: Our data shows HG can promote the proliferation of RMCs and RH has an inhibitory effect on HG-induced RMC proliferation and expression of ECM. Based on our data, we hypothesize this inhibitory effect might be a result of cell cycle regulation and the induction of cellular apoptosis. CONCLUSION: RH can inhibit cellular proliferation and downregulate the expression of ECM under the circumstance of HG. The mechanism of growth suppression may be due to cell cycle arrest at G1 phase, induction of cell apoptosis, and upregulation of apoptotic mediators bax and caspase-3. SUMMARY: Rhein (RH) has an inhibitory effect on high glucose.induced rat mesangial cells proliferationRH has an inhibitory effect on the expression of extracellular matrixRH has a growth.suppression effectRH can upregulate the expression of apoptotic mediators bax and caspase-3All above shows RH is one of the main active ingredient in Shenkang injection. Abbreviations used: RH: Rhein, ECM: Extracellular matrix, DN: Diabetic nephropathy, RMC: Renal mesangial cell, SKI: Shenkang injection, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide. PMID- 27279718 TI - Simultaneous Determination of Eight Bioactive Compounds in Dianthus superbus by High-performance Liquid Chromatography. AB - BACKGROUND: Dianthus superbus, one of traditional herbal medicine, is widely used to treat urethritis, carbuncles and carcinoma. OBJECTIVE: A simultaneous determination method was established for controlling the quality of D. superbus using the eight compounds, (E)-methyl-4-hydroxy-4-(8a-methyl-3 oxodecahydronaphthalen-4a-yl) (1), diosmetin-7-O(2'',6''-di-O-alpha-L rhamnopyranosyl)-beta-D-glucopyranoside (2), vanillic acid (3), 4-hydroxyphenyl acetic acid (4), 4-methoxyphenyl acetic acid (5), (E)-4-methoxycinnamic acid (6), 3-methoxy-4-hydroxyphenylethanol (7), and methyl hydroferulate (8) isolated from D. superbus. MATERIALS AND METHODS: This analysis method was developed using high performance liquid chromatography coupled with diode array detector with a Shishedo C18 column at a column temperature of 3 degrees C. The mobile phase was composed of 0.1% trifluoroacetic acid in water and acetonitrile. The flow rate was 1 ml/min and detection wavelength was set at 205 nm and 280 nm. Validation was performed in order to demonstrate selectivity, accuracy and precision of the method. RESULTS: The calibration curves showed good linearity (R (2) > 0.99). The limits of detection and limits of quantification were within the ranges 0.0159 0.6205 MUg/ml and 0.3210-1.8802 MUg/ml, respectively. Moreover, the relative standard deviations of intra- and inter-day precision were both <2.98%. The overall recoveries were in the range of 96.23-109.87%. Quantitative analysis of eight compounds in 12 D. superbus samples (D-1-D-12) from various regions were analyzed and compared by developed method. CONCLUSION: As a result, this established method was accurate and sensitive for the quality evaluation of eight compounds isolated from D. superbus and may provide a new basis for quality control of D. superbus. SUMMARY: A simultaneous determination method of eight compounds in Dianthus superbus was established by high performance liquid chromatography-diode array detectorDeveloped analysis method is validated with linearity, precious and accuracyThe newly established method was successfully evaluated contents of eight compounds in 12 D. superbus samples (D.1.D.12) from various regions and compared. Abbreviations used: HPLC: High performance liquid chromatography, LOD: Limits of detection, LOQ: Limits of quantification, RSD: Relative standard deviation. PMID- 27279719 TI - Quantitative Analysis and Comparison of Four Major Flavonol Glycosides in the Leaves of Toona sinensis (A. Juss.) Roemer (Chinese Toon) from Various Origins by High-Performance Liquid Chromatography-Diode Array Detector and Hierarchical Clustering Analysis. AB - BACKGROUND: Toona sinensis (A. Juss.) Roemer is an endemic species of Toona genus native to Asian area. Its dried leaves are applied in the treatment of many diseases; however, few investigations have been reported for the quantitative analysis and comparison of major bioactive flavonol glycosides in the leaves harvested from various origins. OBJECTIVE: To quantitatively analyze four major flavonol glycosides including rutinoside, quercetin-3-O-beta-D-glucoside, quercetin-3-O-alpha-L-rhamnoside, and kaempferol-3-O-alpha-L-rhamnoside in the leaves from different production sites and classify them according to the content of these glycosides. MATERIALS AND METHODS: A high-performance liquid chromatography-diode array detector (HPLC-DAD) method for their simultaneous determination was developed and validated for linearity, precision, accuracy, stability, and repeatability. Moreover, the method established was then employed to explore the difference in the content of these four glycosides in raw materials. Finally, a hierarchical clustering analysis was performed to classify 11 voucher specimens. RESULTS: The separation was performed on a Waters XBridge Shield RP18 column (150 mm * 4.6 mm, 3.5 MUm) kept at 35 degrees C, and acetonitrile and H2O containing 0.30% trifluoroacetic acid as mobile phase was driven at 1.0 mL/min during the analysis. Ten microliters of solution were injected and 254 nm was selected to monitor the separation. A strong linear relationship between the peak area and concentration of four analytes was observed. And, the method was also validated to be repeatable, stable, precise, and accurate. CONCLUSION: An efficient and reliable HPLC-DAD method was established and applied in the assays for the samples from 11 origins successfully. Moreover, the content of those flavonol glycosides varied much among different batches, and the flavonoids could be considered as biomarkers to control the quality of Chinese Toon. SUMMARY: Four major flavonol glycosides in the leaves of Toona sinensis were determined by HPLC-DAD and their contents were compared among various origins by HCA. Abbreviations used: HPLC-DAD: High performance liquid chromatography-diode array detector, HCA: Hierarchical clustering analysis, MS: Mass spectrometry, RSD: Relative standard deviation. PMID- 27279720 TI - Optimization Extraction Process of Polysaccharides from Suillus granulatus and Their Antioxidant and Immunological Activities In vitro. AB - BACKGROUND: Suillus granulatus is an edible and medicinal fungus in China. S. granulatus polysaccharide (SGP) was considered as the main bioactivity compounds in S. granulatus. Therefore, the extraction of SGP and their antioxidant activities were studied in this work. MATERIALS AND METHODS: Fruiting bodies of S. granulatus were purchased from a local market (Fushun, China). Response surface methodology was adopted to optimize the extraction conditions of SGP. The antioxidant and immunological activities in vitro were also assayed. RESULTS: The extraction of SGP was optimized by a Box-Behnken design. The optimal conditions for the extraction of polysaccharides were as follows: Pre-extraction time, 2 h; extraction temperature, 94 degrees C; ratio of water to raw material, 25; and extraction frequency, 2. Under these conditions, the experimental yield of polysaccharides was 5.38% +/-0.15%, which agreed with the predicted yield. The antioxidant assay in vitro showed that SGPs had relatively high scavenging ability for hydroxyl radicals and higher scavenging ability for 1,1-diphenyl-2 picrylhydrazyl radical. However, the scavenging ability of SGPs for superoxide anion radical and reducing power was relatively low. The polysaccharides also significantly increased splenocyte proliferation in vitro. CONCLUSION: SGP possessed good antioxidant and immunological activities in vitro and explored as a novel natural antioxidant or functional food. SUMMARY: The predictive model of Suillus granulatus polysaccharide (SGP) extraction is adequate for the extraction processSGP possessed a good antioxidant activity in vitroLymphocyte proliferation in vitro was significantly increased by SGPPictorial abstract (in MS Powerpoint Format) is submitted as a separated file in the online submission system. Abbreviation used: SGP: Suillus granulatus polysaccharides, RSM: Response surface methodology, BBD: Box-Behnken design, Vc: Ascorbic acid, DPPH: 1,1-diphenyl-2 picrylhydrazyl, MTT: 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, ConA: Concanavalin A, LPS: lipopolysaccharide, RPMI-1640: Roswell Park Memorial Institute-1640. PMID- 27279721 TI - Chromatographic and Spectrophotometric Analysis of Phenolic Compounds from Fruits of Libidibia ferrea Martius. AB - BACKGROUND: Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz (Fabaceae) is a tree which is native to Brazil, widely known as "Juca," where its herbal derivatives are used in folk medicine with several therapeutic properties. The constituents, which have already been described in the fruit, are mainly hydrolysable tannins (gallic acid [GA] and ellagic acid [EA]). OBJECTIVE: The aim of this study was to investigate the phenolic variability in the fruit of L. ferrea by ultraviolet/visible (UV/VIS) and chromatographic methods (high-performance liquid chromatography [HPLC]/high-performance thin layer chromatography [HPTLC]). MATERIALS AND METHODS: Several samples were collected from different regions of Brazil and the qualitative (fingerprints by HPTLC and HPLC) and quantitative analysis (UV/VIS and HPLC) of polyphenols were performed. RESULTS: The HPTLC and HPLC profiles allowed separation and identification of both major analytical markers: EA and GA. The chemical profiles were similar in a number of spots or peaks for the samples, but some differences could be observed in the intensity or area of the analytical markers for HPTLC or HPLC, respectively. Regarding the quantitative analysis, the polyphenolic content by UV/VIS ranged from 13.99 to 37.86 g% expressed as GA or from 10.75 to 29.09 g% expressed as EA. The contents of EA and GA by liquid chromatography-reversed phase (LC-RP) method ranged from 0.57 to 2.68 g% and from 0.54 to 3.23 g%, respectively. CONCLUSION: The chemical profiles obtained by HPTLC or HPLC, as well as the quantitative analysis by spectrophotometry or LC-RP method, were suitable for discrimination of each herbal sample and can be used as tools for the comparative analysis of the fruits from L. ferrea. SUMMARY: The polyphenols of fruits of Libidibia ferrea can be quantified by UV/VIS and HPLCThe HPLC method was able to detect the gallic and ellagic acids in several samples of fruits of Libidibia ferreaThe phenolic profiles of fruits from Libidibia ferrea by HPTLC and HPLC were reproductible. Abbreviations used: HPTLC: high performance thin layer chromatography, HPLC: high performance liquid chromatography, UV-Vis: spectrophotometry. PMID- 27279722 TI - Carcinoma Gallbladder- an Indian Problem. PMID- 27279724 TI - Rapidly Mixing Gibbs Sampling for a Class of Factor Graphs Using Hierarchy Width. AB - Gibbs sampling on factor graphs is a widely used inference technique, which often produces good empirical results. Theoretical guarantees for its performance are weak: even for tree structured graphs, the mixing time of Gibbs may be exponential in the number of variables. To help understand the behavior of Gibbs sampling, we introduce a new (hyper)graph property, called hierarchy width. We show that under suitable conditions on the weights, bounded hierarchy width ensures polynomial mixing time. Our study of hierarchy width is in part motivated by a class of factor graph templates, hierarchical templates, which have bounded hierarchy width-regardless of the data used to instantiate them. We demonstrate a rich application from natural language processing in which Gibbs sampling provably mixes rapidly and achieves accuracy that exceeds human volunteers. PMID- 27279725 TI - Using Public-Private Partnerships to Mitigate Disparities in Access to Genetic Services: Lessons from Wisconsin. AB - PURPOSE: This mixed-methods study reports on an outreach clinics program designed to deliver genetic services to medically underserved communities in Wisconsin. METHODOLOGY: We show the geographic distribution, funding patterns, and utilization trends for outreach clinics over a 20-year period. Interviews with program planners and outreach clinic staff show how external and internal constraints limited the program's capacity. We compare clinic operations to the conceptual models guiding program design. FINDINGS: Our findings show that state health officials had to scale back financial support for outreach clinic activities while healthcare providers faced increasing pressure from administrators to reduce investments in charity care. These external and internal constraints led to a decline in the overall number of patients served. We also find that redistribution of clinics to the Milwaukee area increased utilization among Hispanics but not among African-Americans. Our interviews suggest that these patterns may be a function of shortcomings embedded in the planning models. IMPLICATIONS: Planning models have three shortcomings. First, they do not identify the mitigation of health disparities as a specific goal. Second, they fail to acknowledge that partners face escalating profit-seeking mandates that may limit their capacity to provide charity services. Finally, they underemphasize the importance of seeking trusted partners, especially in working with communities that have been historically marginalized. CONTRIBUTION: There has been little discussion about equitably leveraging genetic advances that improve healthcare quality and efficacy. The role of State Health Agencies in mitigating disparities in access to genetic services has been largely ignored in the sociological literature. PMID- 27279726 TI - Measuring the "Sandwich": Care for Children and Adults in the American Time Use Survey 2003-2012. AB - While the economic burden of simultaneously caring for young and old family members is widely recognized, it has yet to be accurately measured. Yet, such assessments are relevant both to public policies providing support to family caregivers and to private insurance markets for long-term care. This descriptive study presents a new method to address this problem: the construction of a crosswalk between time-use diaries and other types of surveys using lists of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) for which assistance is required. Analysis of pooled data from American time use survey 2003-2012 provides some quantitative indicators, but understates the temporal burden of care and fails to distinguish types of care that involve personal interaction from those that do not. A crosswalk of time-use survey categories with the list-based approach typically applied in public health surveys clearly demonstrates the importance of clear definitions and also offers more precise measures. Depending on how sandwich caregiving was defined, the temporal burden for caregiving ranged from 11.2 to 60 h per week, clustering at around 20 h per week for most cases. This result demonstrates the magnitude of sandwich care demands and also underscores the need for improved care survey design. As shown in this study, such efforts should take into account the implications of disaggregating data by gender and age, and definitional variations that characterize existing datasets. PMID- 27279727 TI - Transcriptome analysis of aging mouse meibomian glands. AB - PURPOSE: Dry eye disease is a common condition associated with age-related meibomian gland dysfunction (ARMGD). We have previously shown that ARMGD occurs in old mice, similar to that observed in human patients with MGD. To begin to understand the mechanism underlying ARMGD, we generated transcriptome profiles of eyelids excised from young and old mice of both sexes. METHODS: Male and female C57BL/6 mice were euthanized at ages of 3 months or 2 years and their lower eyelids removed, the conjunctival epithelium scrapped off, and the tarsal plate, containing the meibomian glands, dissected from the overlying muscle and lid epidermis. RNA was isolated, enriched, and transcribed into cDNA and processed to generate four non-stranded libraries with distinct bar codes on each adaptor. The libraries were then sequenced and mapped to the mm10 reference genome, and expression results were gathered as reads per length of transcript in kilobases per million mapped reads (RPKM) values. Differential gene expression analyses were performed using CyberT. RESULTS: Approximately 55 million reads were generated from each library. Expression data indicated that about 15,000 genes were expressed in these tissues. Of the genes that showed more than twofold significant differences in either young or old tissue, 698 were identified as differentially expressed. According to the Gene Ontology (GO) analysis, the cellular, developmental, and metabolic processes were found to be highly represented with Wnt function noted to be altered in the aging mouse. CONCLUSIONS: The RNA sequencing data identified several signaling pathways, including fibroblast growth factor (FGF) and Wnt that were altered in the meibomian glands of aging mice. PMID- 27279729 TI - Bipartite Graphs for Visualization Analysis of Microbiome Data. AB - Visualization analysis plays an important role in metagenomics research. Proper and clear visualization can help researchers get their first insights into data and by selecting different features, also revealing and highlighting hidden relationships and drawing conclusions. To prevent the resulting presentations from becoming chaotic, visualization techniques have to properly tackle the high dimensionality of microbiome data. Although a number of different methods based on dimensionality reduction, correlations, Venn diagrams, and network representations have already been published, there is still room for further improvement, especially in the techniques that allow visual comparison of several environments or developmental stages in one environment. In this article, we represent microbiome data by bipartite graphs, where one partition stands for taxa and the other stands for samples. We demonstrated that community detection is independent of taxonomical level. Moreover, focusing on higher taxonomical levels and the appropriate merging of samples greatly helps improving graph organization and makes our presentations clearer than other graph and network visualizations. Capturing labels in the vertices also brings the possibility of clearly comparing two or more microbial communities by showing their common and unique parts. PMID- 27279728 TI - The Simple Chordate Ciona intestinalis Has a Reduced Complement of Genes Associated with Fanconi Anemia. AB - Fanconi anemia (FA) is a human genetic disease characterized by congenital defects, bone marrow failure, and increased cancer risk. FA is associated with mutation in one of 24 genes. The protein products of these genes function cooperatively in the FA pathway to orchestrate the repair of DNA interstrand cross-links. Few model organisms exist for the study of FA. Seeking a model organism with a simpler version of the FA pathway, we searched the genome of the simple chordate Ciona intestinalis for homologs of the human FA-associated proteins. BLAST searches, sequence alignments, hydropathy comparisons, maximum likelihood phylogenetic analysis, and structural modeling were used to infer the likelihood of homology between C. intestinalis and human FA proteins. Our analysis indicates that C. intestinalis indeed has a simpler and potentially functional FA pathway. The C. intestinalis genome was searched for candidates for homology to 24 human FA and FA-associated proteins. Support was found for the existence of homologs for 13 of these 24 human genes in C. intestinalis. Members of each of the three commonly recognized FA gene functional groups were found. In group I, we identified homologs of FANCE, FANCL, FANCM, and UBE2T/FANCT. Both members of group II, FANCD2 and FANCI, have homologs in C. intestinalis. In group III, we found evidence for homologs of FANCJ, FANCO, FANCQ/ERCC4, FANCR/RAD51, and FANCS/BRCA1, as well as the FA-associated proteins ERCC1 and FAN1. Evidence was very weak for the existence of homologs in C. intestinalis for any other recognized FA genes. This work supports the notion that C. intestinalis, as a close relative of vertebrates, but having a much reduced complement of FA genes, offers a means of studying the function of certain FA proteins in a simpler pathway than that of vertebrate cells. PMID- 27279730 TI - A Bayesian Nonparametric Approach for Functional Data Classification with Application to Hepatic Tissue Characterization. AB - Computed tomography perfusion (CTp) is an emerging functional imaging technology that provides a quantitative assessment of the passage of fluid through blood vessels. Tissue perfusion plays a critical role in oncology due to the proliferation of networks of new blood vessels typical of cancer angiogenesis, which triggers modifications to the vasculature of the surrounding host tissue. In this article, we consider a Bayesian semiparametric model for the analysis of functional data. This method is applied to a study of four interdependent hepatic perfusion CT characteristics that were acquired under the administration of contrast using a sequence of repeated scans over a period of 590 seconds. More specifically, our modeling framework facilitates borrowing of information across patients and tissues. Additionally, the approach enables flexible estimation of temporal correlation structures exhibited by mappings of the correlated perfusion biomarkers and thus accounts for the heteroskedasticity typically observed in those measurements, by incorporating change-points in the covariance estimation. This method is applied to measurements obtained from regions of liver surrounding malignant and benign tissues, for each perfusion biomarker. We demonstrate how to cluster the liver regions on the basis of their CTp profiles, which can be used in a prediction context to classify regions of interest provided by future patients, and thereby assist in discriminating malignant from healthy tissue regions in diagnostic settings. PMID- 27279731 TI - Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus. AB - Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time. PMID- 27279732 TI - A Novel Approach to Predict Core Residues on Cancer-Related DNA-Binding Domains. AB - Protein-DNA interactions are involved in different cancer pathways. In particular, the DNA-binding domains of proteins can determine where and how gene regulatory regions are bound in different cell lines at different stages. Therefore, it is essential to develop a method to predict and locate the core residues on cancer-related DNA-binding domains. In this study, we propose a computational method to predict and locate core residues on DNA-binding domains. In particular, we have selected the cancer-related DNA-binding domains for in depth studies, namely, winged Helix Turn Helix family, homeodomain family, and basic Helix-Loop-Helix family. The results demonstrate that the proposed method can predict the core residues involved in protein-DNA interactions, as verified by the existing structural data. Given its good performance, various aspects of the method are discussed and explored: for instance, different uses of prediction algorithm, different protein domains, and hotspot threshold setting. PMID- 27279733 TI - On the Conflicting Estimations of Pigment Site Energies in Photosynthetic Complexes: A Case Study of the CP47 Complex. AB - We focus on problems with elucidation of site energies [Formula: see text] for photosynthetic complexes (PSCs) in order to raise some genuine concern regarding the conflicting estimations propagating in the literature. As an example, we provide a stern assessment of the site energies extracted from fits to optical spectra of the widely studied CP47 antenna complex of photosystem II from spinach, though many general comments apply to other PSCs as well. Correct values of [Formula: see text] for chlorophyll (Chl) a in CP47 are essential for understanding its excitonic structure, population dynamics, and excitation energy pathway(s). To demonstrate this, we present a case study where simultaneous fits of multiple spectra (absorption, emission, circular dichroism, and nonresonant hole-burned spectra) show that several sets of parameters can fit the spectra very well. Importantly, we show that variable emission maxima (690-695 nm) and sample-dependent bleaching in nonresonant hole-burning spectra reported in literature could be explained, assuming that many previously studied CP47 samples were a mixture of intact and destabilized proteins. It appears that the destabilized subpopulation of CP47 complexes could feature a weakened hydrogen bond between the 13(1)-keto group of Chl29 and the PsbH protein subunit, though other possibilities cannot be entirely excluded, as discussed in this work. Possible implications of our findings are briefly discussed. PMID- 27279734 TI - Gentamicin-Impregnated Collagen Sponge: Effectiveness in Preventing Sternal Wound Infection in High-Risk Cardiac Surgery. AB - Sternal wound infections represent one of the most frequent complications after cardiac surgery and are associated with high postoperative mortality. Several preventive methods have been introduced, and recently, gentamicin-impregnated collagen sponges (GICSs) have shown a promising effect in reducing the incidence of this type of complications. Gentamicin is an aminoglycoside antibiotic that has been widely used to treat infections caused by multiresistant bacteria; despite its effectiveness, its systemic use carries a risk of toxicity. GICSs appear to overcome this side effect, topically delivering high antibiotic concentrations to the wound and thus reducing the toxic-related events. Although several retrospective analyses and randomized controlled trials have studied the use of GICSs in cardiac surgery, conclusions regarding their efficacy in preventing sternal wound infection are inconsistent. We have reviewed the current literature focusing on high-risk patients. PMID- 27279735 TI - Medication adherence in patients in treatment for rheumatoid arthritis and systemic lupus erythematosus in a university hospital in Brazil. AB - Medication adherence is essential for the control of symptoms and progression of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The aim of the study was to investigate medication adherence in outpatients in treatment for RA and SLE in a university hospital in Brazil. This was a quantitative, cross sectional analytical study. A total of 92 patients (55 RA patients and 37 SLE patients) were included in the study. A structured questionnaire for patients' interview and a form for collecting data from medical records were used for data collection. Adherence to drug treatment was assessed by the Morisky scale questionnaire. Data storage and analysis were performed using Epi Info 3.5.4 and statistical analysis by Stata/SE 12.0. The Pearson's chi-squared test and Fisher's exact test were applied for statistical and bivariate analyses. For multivariate data analysis the Poisson regression and the Wald test were used. The prevalence of adherence to drug treatment was 16.4% in RA patients and 45.9% in SLE patients. The final model of the multivariate analysis demonstrated associations between medication adherence and the following covariates for both RA and SLE groups: duration of therapy for rheumatic disease at the institution greater than 15 years and presence of more than six chronic comorbidities. The parameter "acquisition of medication at the high-cost pharmacy" was differently associated with medication adherence by group, and for the SLE group, living outside the city of Goiania was a protective factor associated with adherence. This study demonstrated a low prevalence of medication adherence in patients in treatment for RA and SLE treated at this institution. These findings will serve as a base for future studies to elucidate what factors may positively or negatively affect medication adherence in this population. In addition, multidisciplinary approaches are needed to enhance adherence to drug treatment in patients in treatment for rheumatic disease. PMID- 27279736 TI - Genome Data Exploration Using Correspondence Analysis. AB - Recent developments of sequencing technologies that allow the production of massive amounts of genomic and genotyping data have highlighted the need for synthetic data representation and pattern recognition methods that can mine and help discovering biologically meaningful knowledge included in such large data sets. Correspondence analysis (CA) is an exploratory descriptive method designed to analyze two-way data tables, including some measure of association between rows and columns. It constructs linear combinations of variables, known as factors. CA has been used for decades to study high-dimensional data, and remarkable inferences from large data tables were obtained by reducing the dimensionality to a few orthogonal factors that correspond to the largest amount of variability in the data. Herein, I review CA and highlight its use by considering examples in handling high-dimensional data that can be constructed from genomic and genetic studies. Examples in amino acid compositions of large sets of species (viruses, phages, yeast, and fungi) as well as an example related to pairwise shared orthologs in a set of yeast and fungal species, as obtained from their proteome comparisons, are considered. For the first time, results show striking segregations between yeasts and fungi as well as between viruses and phages. Distributions obtained from shared orthologs show clusters of yeast and fungal species corresponding to their phylogenetic relationships. A direct comparison with the principal component analysis method is discussed using a recently published example of genotyping data related to newly discovered traces of an ancient hominid that was compared to modern human populations in the search for ancestral similarities. CA offers more detailed results highlighting links between modern humans and the ancient hominid and their characterizations. Compared to the popular principal component analysis method, CA allows easier and more effective interpretation of results, particularly by the ability of relating individual patterns with their corresponding characteristic variables. PMID- 27279738 TI - Quality Assessment of Domesticated Animal Genome Assemblies. AB - The era of high-throughput sequencing has made it relatively simple to sequence genomes and transcriptomes of individuals from many species. In order to analyze the resulting sequencing data, high-quality reference genome assemblies are required. However, this is still a major challenge, and many domesticated animal genomes still need to be sequenced deeper in order to produce high-quality assemblies. In the meanwhile, ironically, the extent to which RNAseq and other next-generation data is produced frequently far exceeds that of the genomic sequence. Furthermore, basic comparative analysis is often affected by the lack of genomic sequence. Herein, we quantify the quality of the genome assemblies of 20 domesticated animals and related species by assessing a range of measurable parameters, and we show that there is a positive correlation between the fraction of mappable reads from RNAseq data and genome assembly quality. We rank the genomes by their assembly quality and discuss the implications for genotype analyses. PMID- 27279737 TI - Unmasking Upstream Gene Expression Regulators with miRNA-corrected mRNA Data. AB - Expressed micro-RNA (miRNA) affects messenger RNA (mRNA) abundance, hindering the accuracy of upstream regulator analysis. Our objective was to provide an algorithm to correct such bias. Large mRNA and miRNA analyses were performed on RNA extracted from bovine liver and mammary tissue. Using four levels of target scores from TargetScan (all miRNA:mRNA target gene pairs or only the top 25%, 50%, or 75%). Using four levels of target scores from TargetScan (all miRNA:mRNA target gene pairs or only the top 25%, 50%, or 75%) and four levels of the magnitude of miRNA effect (ME) on mRNA expression (30%, 50%, 75%, and 83% mRNA reduction), we generated 17 different datasets (including the original dataset). For each dataset, we performed upstream regulator analysis using two bioinformatics tools. We detected an increased effect on the upstream regulator analysis with larger miRNA:mRNA pair bins and higher ME. The miRNA correction allowed identification of several upstream regulators not present in the analysis of the original dataset. Thus, the proposed algorithm improved the prediction of upstream regulators. PMID- 27279739 TI - Oral supplementation with a nutraceutical formulation containing omega-3 fatty acids, vitamins, minerals, and antioxidants in a large series of patients with dry eye symptoms: results of a prospective study. AB - PURPOSE: To assess the benefits and tolerability of a dietary supplement based on omega-3 fatty acids to relieve dry eye symptoms. METHODS: A total of 1,419 patients (74.3% women, mean age 58.9 years) with dry eye syndrome using artificial tears participated in a 12-week prospective study. Patients were instructed to take 3 capsules/day of the nutraceutical formulation (Brudysec((r)) 1.5 g). Study variables were dry eye symptoms (scratchy and stinging sensation, eye redness, grittiness, painful and tired eyes, grating sensation, and blurry vision), conjunctival hyperemia, tear breakup time (TBUT), Schrimer I test, and Oxford grading scheme. RESULTS: At 12 weeks, each dry eye symptom improved significantly (P<0.001), and the use of artificial tears decreased significantly from 3.77 (standard deviation [SD] =2.08) at baseline to 3.45 (SD =1.72) (P<0.01). In addition, the Schirmer test scores and the TBUT increased significantly, and there was an increase in patients grading 0-I in the Oxford scale and a decrease of those grading IV-V. Significant differences in improvements of dry eye symptoms were also found in compliant versus noncompliant patients as well as in those with moderate/severe versus none/mild conjunctival hyperemia. CONCLUSION: Oral omega-3 fatty acids supplementation was an effective treatment for dry eye symptoms. PMID- 27279740 TI - Association between abdominal aortic plaque and coronary artery disease. AB - OBJECTIVE: Currently, the association between abdominal aortic plaques and coronary artery disease (CAD) has not yet been clarified clearly. The purpose of this study was to determine the prevalence of abdominal aortic plaques by ultrasound imaging and to explore its association with CAD in patients undergoing coronary angiography. METHODS: Between October 2014 and June 2015, a prospective study was conducted in the Department of Cardiology at Guangdong General Hospital, Guangzhou, People's Republic of China. Ultrasound scanning of the abdominal aortas was performed in 1,667 consecutive patients undergoing coronary angiography. Clinical characteristics and coronary profile were collected from the patients. RESULTS: Of the 1,667 study patients (male, 68.9%; mean age, 63+/ 11 years) undergoing coronary angiography, 1,268 had CAD. Compared with 399 patients without CAD, 1,268 patients with CAD had higher prevalence of abdominal aortic plaques (37.3% vs 17%, P<0.001). In multivariate analysis, abdominal aortic plaques served as independent factors associated with the presence of CAD (odds ratio =2.08; 95% confidence interval =1.50-2.90; P<0.001). Of the 1,268 patients with CAD, the prevalence of abdominal aortic plaques was 27.0% (98/363) in patients with one-vessel disease, 35.0% (107/306) in patients with two-vessel disease, and 44.7% (268/599) in patients with three-vessel disease. Stepwise increases in the prevalence of abdominal aortic plaque was found depending on the number of stenotic coronary vessels (P<0.001; P-value for trend <0.001). In an ordinal logistic regression model, abdominal aortic plaques served as independent factors associated with the severity of CAD according to the number of stenotic coronary vessels (P<0.001). CONCLUSION: The prevalence of abdominal aortic plaques was higher in patients with CAD than in those without CAD. Abdominal aortic plaque was an independent factor associated with the presence and severity of CAD. PMID- 27279741 TI - Factors associated with postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians. AB - PURPOSE: To identify the factors affecting 30-day postoperative complications and 1-year mortality after surgery for colorectal cancer in octogenarians and nonagenarians. METHODS: Between 2005 and 2014, a total of 204 consecutive patients aged >=80 years who underwent major colorectal surgery were included. RESULTS: One hundred patients were male (49%) and 52 patients had American Society of Anesthesiologists (ASA) score >=3 (25%). Combined surgery was performed in 32 patients (16%). Postoperative complications within 30 days after surgery occurred in 54 patients (26%) and 30-day mortality occurred in five patients (2%). Independent risk factors affecting 30-day postoperative complications were older age (>=90 years, hazard ratio [HR] with 95% confidence interval [CI] =4.95 [1.69-14.47], P=0.004), an ASA score >=3 (HR with 95% CI =4.19 [1.8-9.74], P=0.001), performance of combined surgery (HR with 95% CI =3.1 [1.13-8.46], P=0.028), lower hemoglobin level (<10 g/dL, HR with 95% CI =7.56 [3.07-18.63], P<0.001), and lower albumin level (<3.4 g/dL, HR with 95% CI =3.72 [1.43-9.69], P=0.007). An ASA score >=3 (HR with 95% CI =2.72 [1.15-6.46], P=0.023), tumor-node-metastasis (TNM) stage IV (HR with 95% CI =3.47 [1.44-8.39], P=0.006), and occurrence of postoperative complications (HR with 95% CI =4.42 [1.39-14.09], P=0.012) were significant prognostic factors for 1-year mortality. CONCLUSION: Patient-related factors (older age, higher ASA score, presence of anemia, and lower serum albumin) and procedure-related factors (performance of combined surgical procedure) increased postoperative complications. Avoidance of 30-day postoperative complications may decrease 1-year mortality. PMID- 27279742 TI - Low-dose aripiprazole for refractory burning mouth syndrome. AB - We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID- 27279743 TI - Effect of Jian-Pi-Zhi-Dong Decoction on striatal glutamate and gamma-aminobutyric acid levels detected using microdialysis in a rat model of Tourette syndrome. AB - BACKGROUND: Jian-Pi-Zhi-Dong Decoction (JPZDD) is a dedicated treatment of Tourette syndrome (TS). The balance of neurotransmitters in the cortico-striato pallido-thalamo-cortical network is crucial to the occurrence of TS and related to its severity. This study evaluated the effect of JPZDD on glutamate (Glu) and gamma-aminobutyric acid (GABA) and their receptors in a TS rat model. MATERIALS AND METHODS: Rats were divided into four groups (n=12 each). TS was induced in three of the groups by injecting them with 3,3'-iminodipropionitrile for 7 consecutive days. Two model groups were treated with tiapride (Tia) or JPZDD, while the control and the remaining model group were gavaged with saline. Behavior was assessed by stereotypic score and autonomic activity. Striatal Glu and GABA contents were detected using microdialysis. Expressions of N-methyl-D aspartate receptor 1 and GABAA receptor (GABAAR) were observed using Western blot and real-time polymerase chain reaction. RESULTS: Tia and JPZDD groups had decreased stereotypy compared with model rats; however, the JPZDD group showed a larger decrease in stereotypy than the Tia group at a 4-week time point. In a spontaneous activity test, the total distance of the JPZDD and Tia groups was significantly decreased compared with the model group. The Glu levels of the model group were higher than the control group and decreased with Tia or JPZDD treatment. The GABA level was higher in the model group than the control group. Expressions of GABAAR protein in the model group were higher than in the control group. Treatment with Tia or JPZDD reduced the expression of GABAAR protein. In the case of the mRNA expression, only Tia reduced the expression of N-methyl-D aspartate receptor 1, compared with the model group. CONCLUSION: JPZDD could alleviate impairments in behavior and dysfunctional signaling by downregulating GABAAR in the striatum. We suggest that this acts to maintain the balance of Glu and GABA. PMID- 27279744 TI - Critical evaluation of ceftolozane-tazobactam for complicated urinary tract and intra-abdominal infections. AB - The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane-tazobactam, a novel beta lactam/beta-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3. The addition of tazobactam protects ceftolozane from hydrolysis by irreversibly binding to some beta-lactamase enzymes. Ceftolozane-tazobactam is active against a wide range of Gram-negative pathogens, including extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and multidrug resistant (MDR) Pseudomonas aeruginosa, several streptococcal species, and Bacteroides fragilis. When anaerobic coverage is needed, it should be used in combination with metronidazole. Ceftolozane demonstrates linear pharmacokinetics, low protein binding, and minimal accumulation with repeated dosing. The major pharmacokinetic/pharmacodynamic index for ceftolozane is the percentage of the dosing interval in which the plasma free drug concentration remains higher than the minimum inhibitory concentration (%T.MIC). Phase III clinical trials for the treatment of cUTIs and cIAIs have been completed, showing that it is an effective and safe alternative for the treatment of these infections. The approved dose for cUTIs and cIAIs is 1.5 g (1 g ceftolozane and 500 mg tazobactam) infused over 1 hour every 8 hours. A higher 3 g dose is currently in Phase III trials for the treatment of ventilated nosocomial pneumonia. Dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Current data suggest that ceftolozane-tazobactam is a promising carbapenem-sparing alternative agent for the treatment of cUTIs and cIAIs, including those caused by ESBL-producing Enterobacteriaceae and MDR P. aeruginosa. PMID- 27279745 TI - The potential utilizations of hydrogen as a promising therapeutic strategy against ocular diseases. AB - Hydrogen, one of the most well-known natural molecules, has been used in numerous medical applications owing to its ability to selectively neutralize cytotoxic reactive oxygen species and ameliorate hazardous inflammations. Hydrogen can exert protective effects on various reactive oxygen species-related diseases, including the transplantation-induced intestinal graft injury, chronic inflammation, ischemia-reperfusion injuries, and so on. Especially in the eye, hydrogen has been used to counteract multiple ocular pathologies in the ophthalmological models. Herein, the ophthalmological utilizations of hydrogen are systematically reviewed and the underlying mechanisms of hydrogen-induced beneficial effects are discussed. It is our hope that the protective effects of hydrogen, as evidenced by these pioneering studies, would enrich our pharmacological knowledge about this natural element and cast light into the discovery of a novel therapeutic strategy against ocular diseases. PMID- 27279746 TI - Heads in the Cloud: A Primer on Neuroimaging Applications of High Performance Computing. AB - With larger data sets and more sophisticated analyses, it is becoming increasingly common for neuroimaging researchers to push (or exceed) the limitations of standalone computer workstations. Nonetheless, although high performance computing platforms such as clusters, grids and clouds are already in routine use by a small handful of neuroimaging researchers to increase their storage and/or computational power, the adoption of such resources by the broader neuroimaging community remains relatively uncommon. Therefore, the goal of the current manuscript is to: 1) inform prospective users about the similarities and differences between computing clusters, grids and clouds; 2) highlight their main advantages; 3) discuss when it may (and may not) be advisable to use them; 4) review some of their potential problems and barriers to access; and finally 5) give a few practical suggestions for how interested new users can start analyzing their neuroimaging data using cloud resources. Although the aim of cloud computing is to hide most of the complexity of the infrastructure management from end-users, we recognize that this can still be an intimidating area for cognitive neuroscientists, psychologists, neurologists, radiologists, and other neuroimaging researchers lacking a strong computational background. Therefore, with this in mind, we have aimed to provide a basic introduction to cloud computing in general (including some of the basic terminology, computer architectures, infrastructure and service models, etc.), a practical overview of the benefits and drawbacks, and a specific focus on how cloud resources can be used for various neuroimaging applications. PMID- 27279747 TI - Age-Related Differences in White Matter Integrity in Healthy Human Brain: Evidence from Structural MRI and Diffusion Tensor Imaging. AB - The aim is to investigate the relationship between microstructural white matter (WM) diffusivity indices and macrostructural WM volume (WMV) among healthy individuals (20-85 years). Whole-brain diffusion measures were calculated from diffusion tensor imaging using FMRIB software library while WMV was estimated through voxel-based morphometry, and voxel-based analysis was carried out using tract-based spatial statistics. Our results revealed that mean diffusivity, axial diffusivity, and radial diffusivity had shown good correlation with WMV but not for fractional anisotropy (FA). Voxel-wise tract-based spatial statistics analysis for FA showed a significant decrease in four regions for middle-aged group compared to young-aged group, in 22 regions for old-aged group compared to middle-aged group, and in 26 regions for old-aged group compared to young-aged group (P < 0.05). We found significantly lower WMV, FA, and mean diffusivity values in females than males and inverted-U trend for FA in males. We conclude differential age- and gender-related changes for structural WMV and WM diffusion indices. PMID- 27279749 TI - Discussion of causes and consequences of sleepiness among college students, 2014. PMID- 27279748 TI - Epidemiological characteristics of chronic fatigue syndrome/myalgic encephalomyelitis in Australian patients. AB - BACKGROUND: No epidemiological investigations have previously been conducted in Australia according to the current clinical definitions of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The aim of this study was to describe sociodemographic and illness characteristics of Australian patients with CFS/ME. METHODS: A cross-sectional survey on the medical history of patients enrolled in an Australian CFS/ME research database between April 2013 and April 2015. Participants were classified according to Fukuda criteria and International Consensus Criteria. RESULTS: A total of 535 patients diagnosed with CFS/ME by a primary care physician were identified. The mean age of all patients was 46.4 years (standard deviation 12.0); the majority were female (78.61%), Caucasian, and highly educated. Of these, 30.28% met Fukuda criteria. A further 31.96% met both Fukuda criteria and International Consensus Criteria. There were 14.58% reporting chronic fatigue but did not meet criteria for CFS/ME and 23.18% were considered noncases due to exclusionary conditions. Within those meeting CFS/ME criteria, the most common events prior to illness included cold or flu, gastrointestinal illness, and periods of undue stress. Of the 60 symptoms surveyed, fatigue, cognitive, and short-term memory symptoms, headaches, muscle and joint pain, unrefreshed sleep, sensory disturbances, muscle weakness, and intolerance to extremes of temperature were the most commonly occurring symptoms (reported by more than two-thirds of patients). Significant differences in symptom occurrence between Fukuda- and International Consensus Criteria-defined cases were also identified. CONCLUSION: This is the first study to summarize sociodemographic and illness characteristics of a cohort of Australian CFS/ME patients. This is vital for identifying potential risk factors and predictors associated with CFS/ME and for guiding decisions regarding health care provision, diagnosis, and management. PMID- 27279750 TI - A STAT6 Intronic Single-Nucleotide Polymorphism is Associated with Clinical Malaria in Ghanaian Children. AB - Malaria pathogenesis may be influenced by IgE responses and cytokine cross regulation. Several mutations in the IL-4/STAT6 signaling pathway can alter cytokine cross-regulation and IgE responses during a Plasmodium falciparum malarial infection. This study investigated the relationship between a STAT6 intronic single-nucleotide polymorphism (rs3024974), total IgE, cytokines, and malaria severity in 238 Ghanaian children aged between 0.5 and 13 years. Total IgE and cytokine levels were measured by ELISA, while genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Compared with healthy controls, heterozygosity protected against clinical malaria: uncomplicated malaria (odds ratios [OR] = 0.13, P < 0.001), severe malarial anemia (OR = 0.18, P < 0.001), and cerebral malaria (OR = 0.39, P = 0.022). Levels of total IgE significantly differed among malaria phenotypes (P = 0.044) and rs3024974 genotypes (P = 0.037). Neither cytokine levels nor IL-6/IL 10 ratios were associated with malaria phenotypes or rs3024974 genotypes. This study suggests a role for rs3024974 in malaria pathogenesis and offers further insights into an IL-4/STAT6 pathway mutation in malaria pathogenesis. PMID- 27279751 TI - Predicting Clinical Outcomes Using Molecular Biomarkers. AB - Over the past 20 years, there has been an exponential increase in the number of biomarkers. At the last count, there were 768,259 papers indexed in PubMed.gov directly related to biomarkers. Although many of these papers claim to report clinically useful molecular biomarkers, embarrassingly few are currently in clinical use. It is suggested that a failure to properly understand, clinically assess, and utilize molecular biomarkers has prevented their widespread adoption in treatment, in comparative benefit analyses, and their integration into individualized patient outcome predictions for clinical decision-making and therapy. A straightforward, general approach to understanding how to predict clinical outcomes using risk, diagnostic, and prognostic molecular biomarkers is presented. In the future, molecular biomarkers will drive advances in risk, diagnosis, and prognosis, they will be the targets of powerful molecular therapies, and they will individualize and optimize therapy. Furthermore, clinical predictions based on molecular biomarkers will be displayed on the clinician's screen during the physician-patient interaction, they will be an integral part of physician-patient-shared decision-making, and they will improve clinical care and patient outcomes. PMID- 27279752 TI - Toxicity of Boswellia dalzielii (Burseraceae) Leaf Fractions Against Immature Stages of Anopheles gambiae (Giles) and Culex quinquefasciatus (Say) (Diptera: Culicidae). AB - Mosquitoes are vectors of several human pathogens, and great attention has recently been placed on insecticides from plant-derived products, in search for mosquito control agents. This study, thus, investigated the potency of Boswellia dalzielii methanol leaf extract and its four fractions as mosquito ovicide, larvicide, and pupicide against Anopheles gambiae and Culex quinquefasciatus. The plant products were tested at the following concentrations: 125, 250, 500, 1000, and 2000 ppm on eggs and 312.5, 625, 1250, and 2500 ppm on the larvae and pupae of the mosquitoes. For results, hatchability of A. gambiae eggs was reduced to 5% with n-hexane fraction at 2000 ppm. Among the plant products tested, n-hexane fraction was most toxic against A. gambiae (LC50 = 385.9 ppm) and C. quinquefasciatus (LC50 = 3394.9 ppm). The n-hexane fraction of B. dalzielii might be used as a mosquitocidal agent in the breeding sites of A. gambiae and C. quinquefasciatus. PMID- 27279753 TI - Case Study: Giant Cell Arteritis with Vertebral Artery Stenosis. AB - In giant cell arteritis (GCA), involvement of the vertebral arteries is rare with reported rates of 3%-4% for ischemic events secondary to vertebral artery stenosis or occlusion for those patients with GCA. This case study describes a patient who initially presented with acute onset of vertigo but was also found to have transient, side-alternating upper limb neurological findings. While initial imaging showed no vascular abnormalities, it was not until GCA was eventually confirmed with a temporal artery biopsy that the initial scans were shown to have bilateral narrowing of the vertebral arteries. While rare, vertebral artery involvement is an important complication to consider in the setting of GCA due to the high rate of associated mortality, despite immunosuppressive therapy. PMID- 27279756 TI - Double Trouble in a Patient with Coronary Ectasia, Bradycardia with Angina: Epiphenomenal or Mechanistic Association. AB - Coronary artery ectasia is a rare angiographical finding, and it accounts for less than 5% of all coronary angiograms. We report a case of a 55-year-old male patient who presented with fatigue and exertional chest pain. Paraclinical tests revealed cardiac ischemia and sinus node dysfunction, as well as coronary artery ectasia without significant coronary stenosis. Factors involved in cardiac ischemia in this context comprise slow flow, poor collateral circulation, microcirculatory dysfunction, lack of adequate exertional coronary vasodilatation, and endothelial dysfunction. Moreover, poor collaterals with rudimentary sinus node artery may explain sinus node dysfunction. Discussion is made in light of the relevant medical literature. PMID- 27279755 TI - Inflammation and Inflammatory Cells in Myocardial Infarction and Reperfusion Injury: A Double-Edged Sword. AB - Myocardial infarction (MI) is the most common cause of cardiac injury, and subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Therefore, inflammation and inflammatory cell infiltration are the hallmarks of MI and reperfusion injury. Ischemic cardiac injury activates the innate immune response via toll-like receptors and upregulates chemokine and cytokine expressions in the infarcted heart. The recruitment of inflammatory cells is a dynamic and superbly orchestrated process. Sequential infiltration of the injured myocardium with neutrophils, monocytes and their descendant macrophages, dendritic cells, and lymphocytes contributes to the initiation and resolution of inflammation, infarct healing, angiogenesis, and ventricular remodeling. Both detrimental effects and a beneficial role in the pathophysiology of MI and reperfusion injury may be attributed to the subset heterogeneity and functional diversity of these inflammatory cells. PMID- 27279754 TI - Differences Regarding Branded HA in Italy, Part 2: Data from Clinical Studies on Knee, Hip, Shoulder, Ankle, Temporomandibular Joint, Vertebral Facets, and Carpometacarpal Joint. AB - OBJECTIVES: The aim of the current study is to collect scientific data on all branded hyaluronic acid (HA) products in Italy that are in use for intra articular (IA) injection in osteoarthritis (OA) compared with that reported in the leaflet. METHODS: An extensive literature research was performed for all articles reporting data on the IA use of HA in OA. Selected studies were taken into consideration only if they are related to products based on HAs that are currently marketed in Italy with the specific joint indication for IA use in patients affected by OA. RESULTS: Sixty-two HA products are marketed in Italy: 30 products are indicated for the knee but only 8 were proved with some efficacy; 9 products were effective for the hip but only 6 had hip indication; 7 products proved to be effective for the shoulder but only 3 had the indication; 5 products proved effective for the ankle but only one had the indication; 6 products were effective for the temporomandibular joint but only 2 had the indication; only 2 proved effective for vertebral facet joints but only 1 had the indication; and 5 products proved effective for the carpometacarpal joint but only 2 had the indication. CONCLUSIONS: There are only a few products with some evidences, while the majority of products remain without proof. Clinicians and regulators should request postmarketing studies from pharmaceuticals to corroborate with that reported in the leaflet and to gather more data, allowing the clinicians to choose the adequate product for the patient. PMID- 27279757 TI - Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease. AB - Pulmonary involvement is common in rheumatoid arthritis (RA) and affects all the components of the lung. Interstitial lung disease (ILD) is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP) pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD. PMID- 27279758 TI - Palliation of Dysphagia in Carcinoma Esophagus. AB - Esophageal carcinoma has a special place in gastrointestinal carcinomas because it contains two main types, namely, squamous cell carcinoma and adenocarcinoma. Carcinoma esophagus patients require some form of palliation because of locally advanced stage or distant metastasis, where it cannot be subjected to curable treatment with surgery and chemoradiation. Many modalities of palliation of dysphagia are available, but the procedure with least morbidity, mortality, and long-term palliation of dysphagia needs to be chosen for the patient. This study aims to discuss the recent trends in palliation of dysphagia with promising results and the most suitable therapy for palliation of dysphagia in a given patient. A total of 64 articles that were published between years 2005 and 2015 on various modes of palliation of dysphagia in carcinoma esophagus were studied, which were mainly randomized and prospective studies. Through this study, we conclude that stents are the first choice of therapy for palliation, which is safe and cost-effective, and they can be combined with either radiotherapy or chemotherapy for long-term palliation of dysphagia with good quality of life. Radiotherapy can be used as a second-line treatment modality. PMID- 27279759 TI - Universal Pulse Oximetry Screening for Early Detection of Critical Congenital Heart Disease. AB - Critical congenital heart disease (CCHD) is a major cause of infant death and morbidity worldwide. An early diagnosis and timely intervention can significantly reduce the likelihood of an adverse outcome. However, studies from the United States and other developed countries have shown that as many as 30%-50% of infants with CCHD are discharged after birth without being identified. This diagnostic gap is likely to be even higher in low-resource countries. Several large randomized trials have shown that the use of universal pulse-oximetry screening (POS) at the time of discharge from birth hospital can help in early diagnosis of these infants. The objective of this review is to share data to show that the use of POS for early detection of CCHD meets the criteria necessary for inclusion to the universal newborn screening panel and could be adopted worldwide. PMID- 27279760 TI - Body Composition, Fitness Status, and Health Behaviors Upon Entering College: An Examination of Female College Students From Diverse Populations. AB - Although poor health-related behaviors that impact development of chronic diseases begin much earlier than when actual disease is evident, few studies have examined health behaviors in college students, who may be at an important transitional period where early intervention could prevent development of chronic diseases. The purpose of this study was to examine health-related factors in female college students (N = 61) by race/ethnicity and weight status. We found significant differences in health profiles between non-Hispanic White (White) and African American students, including greater physical fitness and healthier diets among White students. Overweight/obese students had worse health profiles than healthy BMI students. Furthermore, weight status was significantly associated with cardiovascular fitness. This supports a focus on PA promotion for interventions in the period of emerging adulthood, alongside the other healthy behaviors, to elicit improvements in weight status and potential reduction of chronic disease risks. PMID- 27279762 TI - Checklist of British and Irish Hymenoptera - Platygastroidea. AB - BACKGROUND: A revised checklist of the British and Irish Platygastroidea (Platygastridae) substantially updates the previous comprehensive checklist, dating from 1978. Distribution data (i.e. occurrence in England, Scotland, Wales, Ireland and the Isle of Man) is reported where known. NEW INFORMATION: A total of 381 British and Irish Platygastroidea represents a 47% increase on the number of British and Irish species reported in 1978. PMID- 27279761 TI - Psychosocial Clusters and their Associations with Well-Being and Health: An Empirical Strategy for Identifying Psychosocial Predictors Most Relevant to Racially/Ethnically Diverse Women's Health. AB - BACKGROUND: Strategies for identifying the most relevant psychosocial predictors in studies of racial/ethnic minority women's health are limited because they largely exclude cultural influences and they assume that psychosocial predictors are independent. This paper proposes and tests an empirical solution. METHODS: Hierarchical cluster analysis, conducted with data from 140,652 Women's Health Initiative participants, identified clusters among individual psychosocial predictors. Multivariable analyses tested associations between clusters and health outcomes. RESULTS: A Social Cluster and a Stress Cluster were identified. The Social Cluster was positively associated with well-being and inversely associated with chronic disease index, and the Stress Cluster was inversely associated with well-being and positively associated with chronic disease index. As hypothesized, the magnitude of association between clusters and outcomes differed by race/ethnicity. CONCLUSIONS: By identifying psychosocial clusters and their associations with health, we have taken an important step toward understanding how individual psychosocial predictors interrelate and how empirically formed Stress and Social clusters relate to health outcomes. This study has also demonstrated important insight about differences in associations between these psychosocial clusters and health among racial/ethnic minorities. These differences could signal the best pathways for intervention modification and tailoring. PMID- 27279763 TI - Generic stabilizability for time-delayed feedback control. AB - Time-delayed feedback control is one of the most successful methods to discover dynamically unstable features of a dynamical system in an experiment. This approach feeds back only terms that depend on the difference between the current output and the output from a fixed time T ago. Thus, any periodic orbit of period T in the feedback-controlled system is also a periodic orbit of the uncontrolled system, independent of any modelling assumptions. It has been an open problem whether this approach can be successful in general, that is, under genericity conditions similar to those in linear control theory (controllability), or if there are fundamental restrictions to time-delayed feedback control. We show that, in principle, there are no restrictions. This paper proves the following: for every periodic orbit satisfying a genericity condition slightly stronger than classical linear controllability, one can find control gains that stabilize this orbit with extended time-delayed feedback control. While the paper's techniques are based on linear stability analysis, they exploit the specific properties of linearizations near autonomous periodic orbits in nonlinear systems, and are, thus, mostly relevant for the analysis of nonlinear experiments. PMID- 27279764 TI - Hamiltonian approach to Ehrenfest expectation values and Gaussian quantum states. AB - The dynamics of quantum expectation values is considered in a geometric setting. First, expectation values of the canonical observables are shown to be equivariant momentum maps for the action of the Heisenberg group on quantum states. Then, the Hamiltonian structure of Ehrenfest's theorem is shown to be Lie Poisson for a semidirect-product Lie group, named the Ehrenfest group. The underlying Poisson structure produces classical and quantum mechanics as special limit cases. In addition, quantum dynamics is expressed in the frame of the expectation values, in which the latter undergo canonical Hamiltonian motion. In the case of Gaussian states, expectation values dynamics couples to second-order moments, which also enjoy a momentum map structure. Eventually, Gaussian states are shown to possess a Lie-Poisson structure associated with another semidirect product group, which is called the Jacobi group. This structure produces the energy-conserving variant of a class of Gaussian moment models that have previously appeared in the chemical physics literature. PMID- 27279765 TI - Crack nucleation using combined crystal plasticity modelling, high-resolution digital image correlation and high-resolution electron backscatter diffraction in a superalloy containing non-metallic inclusions under fatigue. AB - A crystal plasticity finite-element model, which explicitly and directly represents the complex microstructures of a non-metallic agglomerate inclusion within polycrystal nickel alloy, has been developed to study the mechanistic basis of fatigue crack nucleation. The methodology is to use the crystal plasticity model in conjunction with direct measurement at the microscale using high (angular) resolution-electron backscatter diffraction (HR-EBSD) and high (spatial) resolution-digital image correlation (HR-DIC) strain measurement techniques. Experimentally, this sample has been subjected to heat treatment leading to the establishment of residual (elastic) strains local to the agglomerate and subsequently loaded under conditions of low cyclic fatigue. The full thermal and mechanical loading history was reproduced within the model. HR EBSD and HR-DIC elastic and total strain measurements demonstrate qualitative and quantitative agreement with crystal plasticity results. Crack nucleation by interfacial decohesion at the nickel matrix/agglomerate inclusion boundaries is observed experimentally, and systematic modelling studies enable the mechanistic basis of the nucleation to be established. A number of fatigue crack nucleation indicators are also assessed against the experimental results. Decohesion was found to be driven by interface tensile normal stress alone, and the interfacial strength was determined to be in the range of 1270-1480 MPa. PMID- 27279766 TI - Topology optimization for three-dimensional electromagnetic waves using an edge element-based finite-element method. AB - This paper develops a topology optimization procedure for three-dimensional electromagnetic waves with an edge element-based finite-element method. In contrast to the two-dimensional case, three-dimensional electromagnetic waves must include an additional divergence-free condition for the field variables. The edge element-based finite-element method is used to both discretize the wave equations and enforce the divergence-free condition. For wave propagation described in terms of the magnetic field in the widely used class of non-magnetic materials, the divergence-free condition is imposed on the magnetic field. This naturally leads to a nodal topology optimization method. When wave propagation is described using the electric field, the divergence-free condition must be imposed on the electric displacement. In this case, the material in the design domain is assumed to be piecewise homogeneous to impose the divergence-free condition on the electric field. This results in an element-wise topology optimization algorithm. The topology optimization problems are regularized using a Helmholtz filter and a threshold projection method and are analysed using a continuous adjoint method. In order to ensure the applicability of the filter in the element wise topology optimization version, a regularization method is presented to project the nodal into an element-wise physical density variable. PMID- 27279767 TI - Surface tension and the Mori-Tanaka theory of non-dilute soft composite solids. AB - Eshelby's theory is the foundation of composite mechanics, allowing calculation of the effective elastic moduli of composites from a knowledge of their microstructure. However, it ignores interfacial stress and only applies to very dilute composites-i.e. where any inclusions are widely spaced apart. Here, within the framework of the Mori-Tanaka multiphase approximation scheme, we extend Eshelby's theory to treat a composite with interfacial stress in the non-dilute limit. In particular, we calculate the elastic moduli of composites comprised of a compliant, elastic solid hosting a non-dilute distribution of identical liquid droplets. The composite stiffness depends strongly on the ratio of the droplet size, R, to an elastocapillary lengthscale, L. Interfacial tension substantially impacts the effective elastic moduli of the composite when [Formula: see text]. When R<3L/2 (R=3L/2) liquid inclusions stiffen (cloak the far-field signature of) the solid. PMID- 27279768 TI - A geostatistical extreme-value framework for fast simulation of natural hazard events. AB - We develop a statistical framework for simulating natural hazard events that combines extreme value theory and geostatistics. Robust generalized additive model forms represent generalized Pareto marginal distribution parameters while a Student's t-process captures spatial dependence and gives a continuous-space framework for natural hazard event simulations. Efficiency of the simulation method allows many years of data (typically over 10 000) to be obtained at relatively little computational cost. This makes the model viable for forming the hazard module of a catastrophe model. We illustrate the framework by simulating maximum wind gusts for European windstorms, which are found to have realistic marginal and spatial properties, and validate well against wind gust measurements. PMID- 27279769 TI - The criterion of subscale sufficiency and its application to the relationship between static capillary pressure, saturation and interfacial areas. AB - Modern imaging techniques, increased simulation capabilities and extended theoretical frameworks, naturally drive the development of multiscale modelling by the question: which new information should be considered? Given the need for concise constitutive relationships and efficient data evaluation; however, one important question is often neglected: which information is sufficient? For this reason, this work introduces the formalized criterion of subscale sufficiency. This criterion states whether a chosen constitutive relationship transfers all necessary information from micro to macroscale within a multiscale framework. It further provides a scheme to improve constitutive relationships. Direct application to static capillary pressure demonstrates usefulness and conditions for subscale sufficiency of saturation and interfacial areas. PMID- 27279770 TI - Adhesion in hydrogel contacts. AB - A generalized thermomechanical model for adhesion was developed to elucidate the mechanisms of dissipation within the viscoelastic bulk of a hyperelastic hydrogel. Results show that in addition to the expected energy release rate of interface formation, as well as the viscous flow dissipation, the bulk composition exhibits dissipation due to phase inhomogeneity morphological changes. The mixing thermodynamics of the matrix and solvent determines the dynamics of the phase inhomogeneities, which can enhance or disrupt adhesion. The model also accounts for the time-dependent behaviour. A parameter is proposed to discern the dominant dissipation mechanism in hydrogel contact detachment. PMID- 27279771 TI - Extended non-local games and monogamy-of-entanglement games. AB - We study a generalization of non-local games-which we call extended non-local games-in which the players, Alice and Bob, initially share a tripartite quantum state with the referee. In such games, the winning conditions for Alice and Bob may depend on the outcomes of measurements made by the referee, on its part of the shared quantum state, in addition to Alice and Bob's answers to randomly selected questions. Our study of this class of games was inspired by the monogamy of-entanglement games introduced by Tomamichel, Fehr, Kaniewski and Wehner, which they also generalize. We prove that a natural extension of the Navascues-Pironio Acin hierarchy of semidefinite programmes converges to the optimal commuting measurement value of extended non-local games, and we prove two extensions of results of Tomamichel et al. concerning monogamy-of-entanglement games. PMID- 27279772 TI - Nonlinear stability analysis of Darcy's flow with viscous heating. AB - The nonlinear stability of a rectangular porous channel saturated by a fluid is here investigated. The aspect ratio of the channel is assumed to be variable. The channel walls are considered impermeable and adiabatic except for the horizontal top which is assumed to be isothermal. The viscous dissipation is acting inside the channel as internal heat generator. A basic throughflow is imposed, and the nonlinear convective stability is investigated by means of the generalized integral transform technique. The neutral stability curve is compared with the one obtained by the linear stability analysis already present in the literature. The growth rate analysis of different unstable modes is performed. The Nusselt number is investigated for several supercritical configurations in order to better understand how the system behaves when conditions far away from neutral stability are considered. The patterns of the neutrally stable convective cells are also reported. Nonlinear simulations support the results obtained by means of the linear stability analysis, confirming that viscous dissipation alone is indeed capable of inducing mixed convection. Low Gebhart or high Peclet numbers lead to a transient overheating of the originally motionless fluid before it settles in its convective steady state. PMID- 27279773 TI - The pulsating orb: solving the wave equation outside a ball. AB - Transient acoustic waves are generated by the oscillations of an object or are scattered by the object. This leads to initial-boundary value problems (IBVPs) for the wave equation. Basic properties of this equation are reviewed, with emphasis on characteristics, wavefronts and compatibility conditions. IBVPs are formulated and their properties reviewed, with emphasis on weak solutions and the constraints imposed by the underlying continuum mechanics. The use of the Laplace transform to treat the IBVPs is also reviewed, with emphasis on situations where the solution is discontinuous across wavefronts. All these notions are made explicit by solving simple IBVPs for a sphere in some detail. PMID- 27279774 TI - Half conformally flat gradient Ricci almost solitons. AB - The local structure of half conformally flat gradient Ricci almost solitons is investigated, showing that they are locally conformally flat in a neighbourhood of any point where the gradient of the potential function is non-null. In opposition, if the gradient of the potential function is null, then the soliton is a steady traceless kappa-Einstein soliton and is realized on the cotangent bundle of an affine surface. PMID- 27279775 TI - Homogenized boundary conditions and resonance effects in Faraday cages. AB - We present a mathematical study of two-dimensional electrostatic and electromagnetic shielding by a cage of conducting wires (the so-called 'Faraday cage effect'). Taking the limit as the number of wires in the cage tends to infinity, we use the asymptotic method of multiple scales to derive continuum models for the shielding, involving homogenized boundary conditions on an effective cage boundary. We show how the resulting models depend on key cage parameters such as the size and shape of the wires, and, in the electromagnetic case, on the frequency and polarization of the incident field. In the electromagnetic case, there are resonance effects, whereby at frequencies close to the natural frequencies of the equivalent solid shell, the presence of the cage actually amplifies the incident field, rather than shielding it. By appropriately modifying the continuum model, we calculate the modified resonant frequencies, and their associated peak amplitudes. We discuss applications to radiation containment in microwave ovens and acoustic scattering by perforated shells. PMID- 27279776 TI - Proteins as templates for complex synthetic metalloclusters: towards biologically programmed heterogeneous catalysis. AB - Despite nature's prevalent use of metals as prosthetics to adapt or enhance the behaviour of proteins, our ability to programme such architectural organization remains underdeveloped. Multi-metal clusters buried in proteins underpin the most remarkable chemical transformations in nature, but we are not yet in a position to fully mimic or exploit such systems. With the advent of copious, relevant structural information, judicious mechanistic studies and the use of accessible computational methods in protein design coupled with new synthetic methods for building biomacromolecules, we can envisage a 'new dawn' that will allow us to build de novo metalloenzymes that move beyond mono-metal centres. In particular, we highlight the need for systems that approach the multi-centred clusters that have evolved to couple electron shuttling with catalysis. Such hybrids may be viewed as exciting mid-points between homogeneous and heterogeneous catalysts which also exploit the primary benefits of biocatalysis. PMID- 27279777 TI - Encoding Gaussian curvature in glassy and elastomeric liquid crystal solids. AB - We describe shape transitions of thin, solid nematic sheets with smooth, preprogrammed, in-plane director fields patterned across the surface causing spatially inhomogeneous local deformations. A metric description of the local deformations is used to study the intrinsic geometry of the resulting surfaces upon exposure to stimuli such as light and heat. We highlight specific patterns that encode constant Gaussian curvature of prescribed sign and magnitude. We present the first experimental results for such programmed solids, and they qualitatively support theory for both positive and negative Gaussian curvature morphing from flat sheets on stimulation by light or heat. We review logarithmic spiral patterns that generate cone/anti-cone surfaces, and introduce spiral director fields that encode non-localized positive and negative Gaussian curvature on punctured discs, including spherical caps and spherical spindles. Conditions are derived where these cap-like, photomechanically responsive regions can be anchored in inert substrates by designing solutions that ensure compatibility with the geometric constraints imposed by the surrounding media. This integration of such materials is a precondition for their exploitation in new devices. Finally, we consider the radial extension of such director fields to larger sheets using nematic textures defined on annular domains. PMID- 27279778 TI - Submesoscale currents in the ocean. AB - This article is a perspective on the recently discovered realm of submesoscale currents in the ocean. They are intermediate-scale flow structures in the form of density fronts and filaments, topographic wakes and persistent coherent vortices at the surface and throughout the interior. They are created from mesoscale eddies and strong currents, and they provide a dynamical conduit for energy transfer towards microscale dissipation and diapycnal mixing. Consideration is given to their generation mechanisms, instabilities, life cycles, disruption of approximately diagnostic force balance (e.g. geostrophy), turbulent cascades, internal-wave interactions, and transport and dispersion of materials. At a fundamental level, more questions remain than answers, implicating a programme for further research. PMID- 27279779 TI - Efficient molecular dynamics using geodesic integration and solvent-solute splitting. AB - We present an approach to Langevin dynamics in the presence of holonomic constraints based on decomposition of the system into components representing geodesic flow, constrained impulse and constrained diffusion. We show that a particular ordering of the components results in an integrator that is an order of magnitude more accurate for configurational averages than existing alternatives. Moreover, by combining the geodesic integration method with a solvent-solute force splitting, we demonstrate that stepsizes of at least 8 fs can be used for solvated biomolecules with high sampling accuracy and without substantially altering diffusion rates, approximately increasing by a factor of two the efficiency of molecular dynamics sampling for such systems. The methods described in this article are easily implemented using the standard apparatus of modern simulation codes. PMID- 27279780 TI - Expansion shock waves in regularized shallow-water theory. AB - We identify a new type of shock wave by constructing a stationary expansion shock solution of a class of regularized shallow-water equations that include the Benjamin-Bona-Mahony and Boussinesq equations. An expansion shock exhibits divergent characteristics, thereby contravening the classical Lax entropy condition. The persistence of the expansion shock in initial value problems is analysed and justified using matched asymptotic expansions and numerical simulations. The expansion shock's existence is traced to the presence of a non local dispersive term in the governing equation. We establish the algebraic decay of the shock as it is gradually eroded by a simple wave on either side. More generally, we observe a robustness of the expansion shock in the presence of weak dissipation and in simulations of asymmetric initial conditions where a train of solitary waves is shed from one side of the shock. PMID- 27279781 TI - Modelling accretion disc and stellar wind interactions: the case of Sgr A. AB - Sgr A* is an ideal target to study low-luminosity accreting systems. It has been recently proposed that properties of the accretion flow around Sgr A* can be probed through its interactions with the stellar wind of nearby massive stars belonging to the S-cluster. When a star intercepts the accretion disc, the ram and thermal pressures of the disc terminate the stellar wind leading to the formation of a bow shock structure. Here, a semi-analytical model is constructed which describes the geometry of the termination shock formed in the wind. With the employment of numerical hydrodynamic simulations, this model is both verified and extended to a region prone to Kelvin-Helmholtz instabilities. Because the characteristic wind and stellar velocities are in ~108 cm s-1 range, the shocked wind may produce detectable X-rays via thermal bremsstrahlung emission. The application of this model to the pericentre passage of S2, the brightest member of the S-cluster, shows that the shocked wind produces roughly a month long X-ray flare with a peak luminosity of L ~ 4 * 1033 erg s-1 for a stellar mass-loss rate, disc number density, and thermal pressure strength of [Formula: see text], nd = 105 cm-3, and alpha = 0.1, respectively. This peak luminosity is comparable to the quiescent X-ray emission detected from Sgr A* and is within the detection capabilities of current X-ray observatories. Its detection could constrain the density and thickness of the disc at a distance of ~3000 gravitational radii from the supermassive black hole. PMID- 27279783 TI - The minimum mass of detectable planets in protoplanetary discs and the derivation of planetary masses from high-resolution observations. AB - We investigate the minimum planet mass that produces observable signatures in infrared scattered light and submillimetre (submm) continuum images and demonstrate how these images can be used to measure planet masses to within a factor of about 2. To this end, we perform multi-fluid gas and dust simulations of discs containing low-mass planets, generating simulated observations at 1.65, 10 and 850 MUm. We show that the minimum planet mass that produces a detectable signature is ~15 M?: this value is strongly dependent on disc temperature and changes slightly with wavelength (favouring the submm). We also confirm previous results that there is a minimum planet mass of ~20 M? that produces a pressure maximum in the disc: only planets above this threshold mass generate a dust trap that can eventually create a hole in the submm dust. Below this mass, planets produce annular enhancements in dust outwards of the planet and a reduction in the vicinity of the planet. These features are in steady state and can be understood in terms of variations in the dust radial velocity, imposed by the perturbed gas pressure radial profile, analogous to a traffic jam. We also show how planet masses can be derived from structure in scattered light and submm images. We emphasize that simulations with dust need to be run over thousands of planetary orbits so as to allow the gas profile to achieve a steady state and caution against the estimation of planet masses using gas-only simulations. PMID- 27279782 TI - Low-radio-frequency eclipses of the redback pulsar J2215+5135 observed in the image plane with LOFAR. AB - The eclipses of certain types of binary millisecond pulsars (i.e. 'black widows' and 'redbacks') are often studied using high-time-resolution, 'beamformed' radio observations. However, they may also be detected in images generated from interferometric data. As part of a larger imaging project to characterize the variable and transient sky at radio frequencies <200 MHz, we have blindly detected the redback system PSR J2215+5135 as a variable source of interest with the Low-Frequency Array (LOFAR). Using observations with cadences of two weeks - six months, we find preliminary evidence that the eclipse duration is frequency dependent (?nu-0.4), such that the pulsar is eclipsed for longer at lower frequencies, in broad agreement with beamformed studies of other similar sources. Furthermore, the detection of the eclipses in imaging data suggests an eclipsing medium that absorbs the pulsed emission, rather than scattering it. Our study is also a demonstration of the prospects of finding pulsars in wide-field imaging surveys with the current generation of low-frequency radio telescopes. PMID- 27279784 TI - Modelling galaxy clustering: halo occupation distribution versus subhalo matching. AB - We model the luminosity-dependent projected and redshift-space two-point correlation functions (2PCFs) of the Sloan Digital Sky Survey (SDSS) Data Release 7 Main galaxy sample, using the halo occupation distribution (HOD) model and the subhalo abundance matching (SHAM) model and its extension. All the models are built on the same high-resolution N-body simulations. We find that the HOD model generally provides the best performance in reproducing the clustering measurements in both projected and redshift spaces. The SHAM model with the same halo-galaxy relation for central and satellite galaxies (or distinct haloes and subhaloes), when including scatters, has a best-fitting chi2/dof around 2-3. We therefore extend the SHAM model to the subhalo clustering and abundance matching (SCAM) by allowing the central and satellite galaxies to have different galaxy halo relations. We infer the corresponding halo/subhalo parameters by jointly fitting the galaxy 2PCFs and abundances and consider subhaloes selected based on three properties, the mass Macc at the time of accretion, the maximum circular velocity Vacc at the time of accretion, and the peak maximum circular velocity Vpeak over the history of the subhaloes. The three subhalo models work well for luminous galaxy samples (with luminosity above L*). For low-luminosity samples, the Vacc model stands out in reproducing the data, with the Vpeak model slightly worse, while the Macc model fails to fit the data. We discuss the implications of the modelling results. PMID- 27279786 TI - Direct collapse to supermassive black hole seeds: comparing the AMR and SPH approaches. AB - We provide detailed comparison between the adaptive mesh refinement (AMR) code enzo-2.4 and the smoothed particle hydrodynamics (SPH)/N-body code gadget-3 in the context of isolated or cosmological direct baryonic collapse within dark matter (DM) haloes to form supermassive black holes. Gas flow is examined by following evolution of basic parameters of accretion flows. Both codes show an overall agreement in the general features of the collapse; however, many subtle differences exist. For isolated models, the codes increase their spatial and mass resolutions at different pace, which leads to substantially earlier collapse in SPH than in AMR cases due to higher gravitational resolution in gadget-3. In cosmological runs, the AMR develops a slightly higher baryonic resolution than SPH during halo growth via cold accretion permeated by mergers. Still, both codes agree in the build-up of DM and baryonic structures. However, with the onset of collapse, this difference in mass and spatial resolution is amplified, so evolution of SPH models begins to lag behind. Such a delay can have effect on formation/destruction rate of H2 due to UV background, and on basic properties of host haloes. Finally, isolated non-cosmological models in spinning haloes, with spin parameter lambda ~ 0.01-0.07, show delayed collapse for greater lambda, but pace of this increase is faster for AMR. Within our simulation set-up, gadget-3 requires significantly larger computational resources than enzo-2.4 during collapse, and needs similar resources, during the pre-collapse, cosmological structure formation phase. Yet it benefits from substantially higher gravitational force and hydrodynamic resolutions, except at the end of collapse. PMID- 27279785 TI - New methods to constrain the radio transient rate: results from a survey of four fields with LOFAR. AB - We report on the results of a search for radio transients between 115 and 190 MHz with the LOw-Frequency ARray (LOFAR). Four fields have been monitored with cadences between 15 min and several months. A total of 151 images were obtained, giving a total survey area of 2275 deg2. We analysed our data using standard LOFAR tools and searched for radio transients using the LOFAR Transients Pipeline. No credible radio transient candidate has been detected; however, we are able to set upper limits on the surface density of radio transient sources at low radio frequencies. We also show that low-frequency radio surveys are more sensitive to steep-spectrum coherent transient sources than GHz radio surveys. We used two new statistical methods to determine the upper limits on the transient surface density. One is free of assumptions on the flux distribution of the sources, while the other assumes a power-law distribution in flux and sets more stringent constraints on the transient surface density. Both of these methods provide better constraints than the approach used in previous works. The best value for the upper limit we can set for the transient surface density, using the method assuming a power-law flux distribution, is 1.3 * 10-3 deg-2 for transients brighter than 0.3 Jy with a time-scale of 15 min, at a frequency of 150 MHz. We also calculated for the first time upper limits for the transient surface density for transients of different time-scales. We find that the results can differ by orders of magnitude from previously reported, simplified estimates. PMID- 27279787 TI - Forming supermassive black hole seeds under the influence of a nearby anisotropic multifrequency source. AB - The photodissociation of H2 by a nearby anisotropic source of radiation is seen as a critical component in creating an environment in which a direct collapse black hole may form. Employing radiative transfer we model the effect of multifrequency (0.76-60 eV) radiation on a collapsing halo at high redshift. We vary both the shape of the spectrum which emits the radiation and the distance to the emitting galaxy. We use blackbody spectra with temperatures of T = 104 K and 105 K and a realistic stellar spectrum. We find that an optimal zone exists between 1 and 4 kpc from the emitting galaxy. If the halo resides too close to the emitting galaxy the photoionizing radiation creates a large H ii region which effectively disrupts the collapsing halo, too far from the source and the radiation flux drops below the level of the expected background and the H2 fraction remains too high. When the emitting galaxy is initially placed between 1 and 2 kpc from the collapsing halo, with a spectral shape consistent with a star forming high-redshift galaxy, then a large central core forms. The mass of the central core is between 5000 and 10 000 M? at a temperature of approximately 1000 K. This core is however surrounded by a reservoir of hotter gas at approximately 8000 K, which leads to mass inflow rates of the order of ~0.1 M? yr-1. PMID- 27279788 TI - ECG-Guided Surveillance Technique in Cryoballoon Ablation for Paroxysmal and Persistent Atrial Fibrillation: A Strategy to Prevent From Phrenic Nerve Palsy. AB - AIMS: Phrenic nerve palsy (PNP) is still a cause for concern in Cryoballoon ablation (CBA) procedures. New surveillance techniques, such as invasive registration of the compound motor action potential (CMAP), have been thought to prevent the occurrence of PNP. The present study investigates the impact of CMAP surveillance via an alternative and non-invasive ECG-conduction technique during CBA. METHODS: PVI with CBA was performed in 166 patients suffering from AF. Diaphragmal contraction was monitored by abdominal hands-on observation in Observation Group I; Observation Group II was treated using additional ECG conduction, as a means of modified CMAP surveillance method. During the ablation of the right superior and inferior pulmonary veins, the upper extremities lead I was newly adjusted between the inferior sternum and the right chest, thereby recording the maximum CMAP. The CMAP in the above-mentioned ECG leads was continuously observed in a semi-quantitative manner. RESULTS: PNP was observed in 10 (6%) patients in total. In Observation Group I, 6 out of 61 (9.8%) demonstrated PNP. In Observation Group II a significant decrease of PNP could be demonstrated (p <0,001) and occurred in 4 out of 105 patients (3.8%). While three patients from Observation Group I left the EP lap with an ongoing PNP, none of the patients in Observation Group II had persistent PNP outside of the EP lab. CONCLUSION: The present study demonstrates that additional ECG-conduction, used as modified CMAP surveillance, is an easy, effective and helpful additional safety measure to prevent PNP in CBA. PMID- 27279789 TI - The Expression of Gli3 and Teashirt3 in the Stenotic Tissue of Congenital Pelvi Ureteric Junction Obstruction in Children. AB - BACKGROUND: The aim of this study was to determine the expression pattern of Gli3 and Teashirt3 in stenotic segments in children with congenital hydronephrosis due to pelvi-ureteric junction obstruction (PUJO) versus in normal control subjects. MATERIALS AND METHODS: 60 patients and 10 controls were included in this study. Immunohistochemistry, Western blot and real-time PCR were used to investigate into the expression of Gli3 and Teashirt3. RESULTS: Immunohistochemistry identified that Gli3 and Teashirt3 located in the cytoplasm of smooth muscle in normal ureter. However, the expression of Gli3 and Teashirt3 was negative in the PUJO group. Gli3 and Teashirt3 protein and mRNA expression was significantly decreased in PUJO group compared with control group on Western blot and real time PCR. CONCLUSIONS: The expression of protein and mRNA of Gli3 and Teashirt3 was significantly decreased in the PUJO group. Gli3 and Teashirt3 protein was mainly located in the cytoplasm of smooth muscle in normal ureter. Gli3 and Teashirt3 might play an important role in the normal development of the ureter. The down regulated Gli3 and Teashirt3 perhaps participated in the pathogenesis of the congenital hydronephrosis due to PUJO. PMID- 27279790 TI - Daclatasvir plus Asunaprevir Treatment for Real-World HCV Genotype 1-Infected Patients in Japan. AB - Background. All-oral combination of direct-acting antivirals could lead to higher sustained virologic response (SVR) in hepatitis C virus (HCV)-infected patients. In the present study, we examined the efficacy and safety of the dual oral treatment with HCV nonstructural protein (NS) 5A inhibitor daclatasvir (DCV) plus HCV NS3/4A inhibitor asunaprevir (ASV) for 24 weeks in real-world HCV genotype 1 infected Japanese individuals. Methods. After screening for HCV NS5A resistance associated variants (RAVs) by PCR invader assay, a total of 54 Japanese patients infected with HCV genotype 1 treated with DCV plus ASV were retrospectively analyzed. SVR12 was used for evaluation of the virologic response. Results. Of the total 54 patients, 46 patients (85.2%) were treated with DCV plus ASV for 24 weeks and achieved SVR12. The other 8 patients (14.8%) discontinued this treatment before 24 weeks due to adverse events. Of these 8 patients, 5 and 3 patients did and did not achieve SVR12, respectively. Finally, 51 of 54 (94.4%) patients achieved SVR12. Conclusion. Treatment with DCV and ASV after screening for HCV NS5A RAVs by PCR invader assay is effective and safe in the treatment of real-world HCV genotype 1-infected patients in Japan. PMID- 27279791 TI - Detection of Human Papillomavirus 16-Specific IgG and IgM Antibodies in Patient Sera: A Potential Indicator of Oral Squamous Cell Carcinoma Risk Factor. AB - The association between human papillomavirus type 16 (HPV16) and oral cancer has been widely reported. However, detecting anti-HPV antibodies in patient sera to determine risk for oral squamous cell carcinoma (OSCC) has not been well studied. In the present investigation, a total of 206 OSCC serum samples from the Malaysian Oral Cancer Database & Tissue Bank System, with 134 control serum samples, were analyzed by enzyme-linked immunosorbant assay (ELISA) to detect HPV16-specific IgG and IgM antibodies. In addition, nested PCR analysis using comprehensive consensus primers (PGMY09/11 and GP5(+)/6(+)) was used to confirm the presence of HPV. Furthermore, we have evaluated the association of various additional causal factors (e.g., smoking, alcohol consumption, and betel quid chewing) in HPV-infected OSCC patients. Statistical analysis of the Malaysian population indicated that OSCC was more prevalent in female Indian patients that practices betel quid chewing. ELISA revealed that HPV16 IgG, which demonstrates past exposure, could be detected in 197 (95.6%) OSCC patients and HPV16-specific IgM was found in a total of 42 (20.4%) OSCC patients, indicating current exposure. Taken together, our study suggest that HPV infection may play a significant role in OSCC (OR: 13.6; 95% CI: 3.89-47.51) and HPV16-specific IgG and IgM antibodies could represent a significant indicator of risk factors in OSCC patients. PMID- 27279792 TI - Study and Therapeutic Progress on Intracranial Serpentine Aneurysms. AB - An intracranial serpentine aneurysm (SA) is a clinically rare entity, and very few multi-case studies on SA have been published. The present study reviewed the relevant literature available on PubMed. The studied information included the formation mechanism and natural history of SA as well as its clinical manifestation, imaging characteristics, and current treatments. After reviewing the literature, we conclude that intracranial SA can be managed surgically and by endovascular embolization, but the degree of blood flow in normal brain tissue distal to the SA must be evaluated. A balloon occlusion test (BOT) or cross compression test is recommended for this evaluation. If the collateral circulation is sufficiently compensatory, direct excision or embolization can be performed. However, if the compensatory collateral circulation is poor, a bypass surgery is necessary. Satisfactory results can be achieved in the majority of SA patients after treatment. However, the size of the aneurysm may increase in some patients after endovascular treatment. Special attention should be paid to cases exhibiting a significant mass effect to avoid subsequent SA excision due to an intolerable mass effect. Satisfactory results can be achieved with careful treatment of SA. PMID- 27279793 TI - Gender Related Survival Differences in ST-Elevation Myocardial Infarction Patients Treated with Primary PCI. AB - BACKGROUND: Data about gender as an independent risk factor for death in ST elevation myocardial infarction (STEMI) patients is still contrasting. Aim was to assess how gender influences in-hospital and long-term all-cause mortality in STEMI patients with primary percutaneous coronary intervention (PCI) in our region. METHODS: We analysed data from 2069 STEMI patients undergoing primary PCI in our institution from January 2009-December 2014, of whom 28.9% were women. In hospital and long-term mortality were observed in women and men. The effect of gender on in-hospital mortality was assessed by binary logistic regression modelling and by Cox regression analysis for long-term mortality. RESULTS: Women were older (68.3+/-61.8 vs 61.8+/-12.0 years; p<0.0001), with a higher prevalence of diabetes (13.7% vs 9.9%; p=0.013) and tend to be more frequently admitted in cardiogenic shock (8.4% vs 6.3%; p =0.085). They were less frequently treated with bivalirudin (15.9% vs 20.3%; p=0.022). In-hospital mortality was higher among women (14.2% vs 7.8%; p<0.0001). After adjustment, age (adjusted OR: 1.05; 95% CI: 1.03 to 1.08; p < 0.001) and cardiogenic shock at admission (adjusted OR: 24.56; 95% CI: 11.98 to 50.35; p < 0.001), but not sex (adjusted OR: 1.47; 95% CI: 0.80 to 2.71) were identified as prognostic factors of in-hospital mortality. During the median follow-up of 27 months (25th, 75th percentile: 9, 48) the mortality rate (23.6% vs 15.1%; p<0.0001) was significantly higher in women. The multivariate adjusted Cox regression model identified age (HR 1.05; 95% CI 1.04 1.07; p<0.0001), cardiogenic shock at admission (HR 6.09; 95% CI 3.78-9.81; p<0.0001), hypertension (HR 1.49; 95% CI 1.02-2.18; p<0.046), but not sex (HR 1.04; 95% CI 0.74-1.47) as independent prognostic factors of follow-up mortality. CONCLUSION: Older age and worse clinical presentation rather than gender may explain the higher mortality rate in women with STEMI undergoing primary PCI. PMID- 27279794 TI - Longitudinal Associations between Triglycerides and Metabolic Syndrome Components in a Beijing Adult Population, 2007-2012. AB - BACKGROUND: Longitudinal associations between triglycerides (TG) and other metabolic syndrome (MetS) components have rarely been reported. The purpose was to investigate the longitudinal association between TG and other MetS components with time. METHODS: The longitudinal study was established in 2007 on individuals who attended health check-ups at Beijing Tongren Hospital and Beijing Xiaotangshan Hospital. Data used in this study was based on 7489 participants who had at least three health check-ups over a period of 5-year follow up. Joint model was used to explore longitudinal associations between TG and other MetS components after adjusted for age. RESULTS: There were positive correlations between TG and other MetS components except for high density lipoprotein (HDL), and the correlations increased with time. A negative correlation was displayed between TG and HDL, and the correlation also increased with time. Among all five pairs of TG and other MetS components, the marginal correlation between TG and body mass index (BMI) was the largest for both men and women. The marginal correlation between TG and fasting plasma glucose was the smallest for men, while the marginal correlation between TG and diastolic blood pressure was the smallest for women. CONCLUSIONS: The longitudinal association between TG and other MetS components increased with time. Among five pairs of TG and other MetS components, the longitudinal correlation between TG and BMI was the largest. It is important to closely monitor subjects with high levels of TG and BMI in health check-up population especially for women, because these two components are closely associated with development of hypertension, diabetes, cardiovascular disease and other metabolic diseases. PMID- 27279795 TI - The Association of -429T>C and -374T>A Polymorphisms in the RAGE Gene with Polycystic Ovary Syndrome. AB - Polycystic ovary syndrome (PCOS) is a complex disorder characterized by hyperandrogenism and insulin resistance. In addition, a number of females with PCOS have ovaries with multiple cysts, an irregular or no menstrual cycle, and an imbalance of female hormones compared to those of normal controls. A variety of genetic factors have been involved in the pathogenesis of PCOS. Among these genetic factors, the receptor for advanced glycation end products (RAGE) that is associated with diabetes and involved in the complications of PCOS, was selected. We aimed to assess the relationship between -429T>C and -374T>A single nucleotide polymorphisms (SNPs) of RAGE gene with the susceptibility to PCOS.128 controls and 265 PCOS patients were used for -374T>A polymorphism and 141 controls and 290 PCOS patients were used for -429T>C polymorphism, respectively. Genotyping of two polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and statistical analysis was performed. P values for both alleles were higher than 0.05. Frequencies of genotype and allele of two polymorphisms in RAGE gene showed no significant differences between controls and PCOS patients. The initial study on the correlation between RAGE gene and PCOS indicates that the two polymorphisms of RAGE are not associated with the pathogenesis of PCOS. However, further studies regarding the association between RAGE gene and PCOS patients in different ethnic groups are required. PMID- 27279797 TI - Efficacy of Honeycomb TCP-induced Microenvironment on Bone Tissue Regeneration in Craniofacial Area. AB - Artificial bone materials that exhibit high biocompatibility have been developed and are being widely used for bone tissue regeneration. However, there are no biomaterials that are minimally invasive and safe. In a previous study, we succeeded in developing honeycomb beta-tricalcium phosphate (beta-TCP) which has through-and-through holes and is able to mimic the bone microenvironment for bone tissue regeneration. In the present study, we investigated how the difference in hole-diameter of honeycomb beta-TCP (hole-diameter: 75, 300, 500, and 1600 MUm) influences bone tissue regeneration histologically. Its osteoconductivity was also evaluated by implantation into zygomatic bone defects in rats. The results showed that the maximum bone formation was observed on the beta-TCP with hole diameter 300MUm, included bone marrow-like tissue and the pattern of bone tissue formation similar to host bone. Therefore, the results indicated that we could control bone tissue formation by creating a bone microenvironment provided by beta-TCP. Also, in zygomatic bone defect model with honeycomb beta-TCP, the result showed there was osseous union and the continuity was reproduced between the both edges of resected bone and beta-TCP, which indicated the zygomatic bone reproduction fully succeeded. It is thus thought that honeycomb beta-TCP may serve as an excellent biomaterial for bone tissue regeneration in the head, neck and face regions, expected in clinical applications. PMID- 27279796 TI - Differential microRNA Profiles Predict Diabetic Nephropathy Progression in Taiwan. AB - OBJECTIVES: Diabetic nephropathy (DN) is a major leading cause of kidney failure. Recent studies showed that serological microRNAs (miRs) could be utilized as biomarkers to identify disease pathogenesis; the DN-related miRs, however, remained to be explored. METHODS: A prospective case-control study was conducted. The clinical significance of five potential miRs (miR-21, miR-29a, miR-29b, miR 29c and miR192) in type 2 Diabetes Mellitus (T2DM) patients who have existing diabetic retinopathy with differential Albumin:Creatinine Ratio (ACR) and estimated Glomerular Filtration Rate (eGFR) was performed using quantitative RT PCR analysis. The subjects with diabetic retinopathy enrolled in Taipei City Hospital, Taiwan, were classified into groups of normal albuminuria (ACR<30mg/g; N=12); microalbuminuria (30mg/g300mg/g; N=21) as well as 18 low-eGFR (eGFR<60ml/min) and 32 high-eGFR (eGFR>60ml/min). The level of serum miRs was statistically correlated with age, Glucose AC, ACR, eGFR and DN progression. RESULTS: The levels of miR-21, miR-29a and miR-192 were significantly enriched in the overt proteinuria group compared with microalbuminuria and/or overt proteinuria groups. It was shown that only miR 21 level was significantly up-regulated in low-eGFR group compared with high-eGFR patients. Interestingly, Pearson's correlation coefficient analysis demonstrated that DN progressors showed significantly greater levels of miR-21, miR-29a, miR 29b and miR-29c in comparison with non-progressors implying the clinical potential of DN associated miRs in monitoring and preventing disease advancement. CONCLUSION: Our findings showed that miR-21, miR-29a/b/c and miR-192 could reflect DN pathogenesis and serve as biomarkers during DN progression. PMID- 27279798 TI - 5-type HPV mRNA versus 14-type HPV DNA test: test performance, over-diagnosis and overtreatment in triage of women with minor cervical lesions. AB - BACKGROUND: Repeat cytology and HPV testing is used in triage of women with minor cytological lesions. The objective of this study was to evaluate 14-type HPV DNA and 5-type HPV mRNA testing in delayed triage of women with ASC-US/LSIL. METHODS: We compared a DNA test (Roche Cobas 4800) and an 5-type mRNA test (PreTect HPV Proofer). In total 564 women were included in the study. RESULTS: The sensitivity among solved cases for CIN3+ were 100 % (15/15) for both tests. The sensitivity for CIN2+ of the HPV DNA test was 100 % (38/38) relative to 79 % (30/38) for the 5-type HPV mRNA test. The corresponding estimates of specificity for CIN2+ among solved cases were 84 % (393/466; 95 % CI: 81-88) and 91 % (451/498; 95 % CI: 88 93). The positive predictive values for CIN3+ were 13.5 % (15/111) for DNA+ and 19.5 % (15/77) for 5-type mRNA+. Significantly more women screened with 5-type mRNA than DNA returned to screening (81 % vs 71 %, p < 0.01). Subsequently, significantly fewer women were referred for colposcopy/biopsies/treatment (19 % (105/564) vs 29 % (165/564), p < 0.01). CONCLUSIONS: 5-type HPV mRNA is more specific than 14-type HPV DNA in delayed triage of women with ASC-US/LSIL. The referral rate for colposcopy was 57 % higher for DNA+ relative to mRNA+ cases (165 vs 105), with the same detection rate of CIN3+, but the 5-type mRNA test had lower sensitivity for CIN2+. It is important to consider the trade-off between sensitivity and specificity of the diagnostic test when designing screening algorithms. PMID- 27279799 TI - Parotid gland, an exceptional localization of sebaceous carcinoma: case report. AB - BACKGROUND: Sebaceous carcinoma (SC) is a rare malignancy, occurring predominantly in eyelids. Till date, only 25 cases of sebaceous carcinoma (SC) of the parotid gland have been reported in world literature. CASE PRESENTATION: A 33 year-old male presented with left sided laterocervical mass. Clinical examination showed enlargement of the left parotid gland, with cervical lymphadenopathy. No skin lesions were found. A resection of the gland was performed. Pathological findings were consistent with primary sebaceous carcinoma of the parotid gland. CONCLUSION: Sebaceous carcinoma of the parotid gland is extremely uncommon. Clinical and radiological features are not specific. The aim of this report, is to describe histopathological, and immunohistochemical findings of this rare entity, and discuss differential diagnosis. PMID- 27279800 TI - Comprehensive characterization of the patient-derived xenograft and the paralleled primary hepatocellular carcinoma cell line. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with high mortality and morbidity worldwide. The limited clinically relevant model has impeded the development of effective HCC treatment strategy. Patient-derived xenograft (PDX) models retain most of the characteristics of original tumors and were shown to be highly predictive for clinical outcomes. Notably, primary cell line models allow in-depth molecular characterization and high-throughput analysis. Combined usage of the two models would provide an excellent tool for systematic study of therapeutic strategies. Here, we comprehensively characterized the novel PDX and the paralleled primary HCC cell line model. METHODS: Tumor tissues were collected from HCC surgical specimens. HCC cells were sorted for in vivo PDX and in vitro cell line establishment by the expression of hepatic cancer stem cell marker to enhance cell viability and the rate of success on subsequent culture. The PDX and its matching primary cell line were authenticated and characterized in vitro and in vivo. RESULTS: Among the successful cases for generating PDXs and primary cells, HCC40 is capable for both PDX and primary cell line establishment, which were then further characterized. The novel HCC40-PDX and HCC40-CL exhibited consistent phenotypic characteristics as the original tumor in terms of HBV protein and AFP expressions. In common with HCC40-PDX, HCC40-CL was tumorigenic in immunocompromised mice. The migration ability in vitro and metastatic properties in vivo echoed the clinical feature of venous infiltration. Genetic profiling by short tandem repeat analysis and p53 mutation pattern consolidated that both the HCC40-PDX and HCC40-CL models were derived from the HCC40 clinical specimen. CONCLUSIONS: The paralleled establishment of PDX and primary cell line would serve as useful models in comprehensive studies for HCC pathogenesis and therapeutics development for personalized treatment. PMID- 27279801 TI - Implementation of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit. AB - The purpose of this study was to examine the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in burn patients with infectious complications. All burn patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections were eligible. Patients were assigned to either a procalcitonin-guided (study group) or a standard (control group) antibiotic regimen. The following variables were analyzed and compared in both groups: duration of antibiotic treatment, mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score (days 1-28), length of ICU and hospital stay. A total of 46 Burn ICU patients receiving antibiotic therapy were enrolled in this study. In 24 patients antibiotic therapy was guided by daily procalcitonin and clinical assessment. PCT guidance resulted in a smaller antibiotic exposure (10.1+/-4 vs. 15.3+/-8 days, p=0.034) without negative effects on clinical outcome characteristics such as mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score, length of ICU and hospital stay. The findings thus show that use of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit may contribute to the reduction of antibiotic exposure without compromising clinical outcome parameters. PMID- 27279802 TI - Prevalence of beta lactamase producing species of pseudomonas and acinetobacter in pediatric burn patients. AB - Burn wound infection is a major cause of morbidity and mortality in burn victims. Pseudomonas and Acinetobacter species are among the most common organisms complicating burn wounds. Presence of extended spectrum beta-lactamase (ESBL) and metallo-beta-lactamase (MBL) genes plays an important role in spreading beta lactam resistant strains of these organisms and is a serious condition in the treatment of the affected patients. As a result, we aimed to determine the prevalence of SHV, TEM, PER and VIM beta-lactamases in Pseudomonas and Acinetobacter species isolates from burn wound swabs of children with burn injury. In this descriptive observational study, 107 Pseudomonas and Acinetobacter isolates collected from burn patients were subjected to PCR assay. Using PCR method and DNA sequencing, the existence of SHV-, TEM-, PER- and VIM type beta-lactamase encoding genes were determined. Out of the 107 Pseudomonas and Acinetobacter isolates, 66 (77.6%) were ESBL positive, 26.2% were positive for SHV gene, 37.4% were positive for TEM gene, 14% were positive for PER gene and 15.9% of them harbored VIM gene. More than half of the Pseudomonas and Acinetobacter strains in our pediatric burn unit harbor beta-lactamase encoding genes that make them resistant to a wide range of beta-lactam antibiotics. Consequently, it is suggested to choose an appropriate antibiotic regimen based on the antibiogram pattern of the strains. PMID- 27279803 TI - Blood transfusion trigger in burns: a four-year retrospective analysis of blood transfusions in eleven burn centers in Ukraine. AB - One focus of improvement of burn care in Ukraine was the management of blood loss and blood transfusions in burn patients. The aim of this project was to analyze blood transfusion triggers in burn patients and outcomes at eleven major burn centers in Ukraine. This multicenter retrospective study reviewed four years of data on blood-transfused burn patients admitted to eleven major burn centers in Ukraine. Data analyzed included: demographics, characteristics of the burns, complications of burn injury, triggers for blood transfusions and outcomes. A total of 928 burn patients who received 2,693 blood transfusions from 11 major burn centers over a four-year period, were studied. Regardless of the total body surface area (TBSA) that was burned, blood transfusions were administered with a hemoglobin (Hb) trigger value of around 9 g/dL. Roughly one third (30.5%) of all transfusions were given in patients with a TBSA <= 10%. We demonstrated that Ukrainian doctors were using the same Hb trigger for blood transfusions for all Ukrainian burn patients, which suggested a need to change blood transfusion policy. PMID- 27279804 TI - Improved survival with an innovative approach to the treatment of severely burned patients: development of a burn treatment manual. AB - The management of severely burned patients remains a major issue worldwide as indicated by the high incidence of permanent debilitating complications and poor survival rates. In April 2012, the Advanced Emergency & Critical Care Medical Center of the Okayama University Hospital began implementing guidelines for severely burned patients, distributed as a standard burn treatment manual. The protocol, developed in-house, was validated by comparing the outcomes of patients with severe extensive burns (SEB) treated before and after implementation of these new guidelines at this institution. The patients included in this study had a burn index (BI) >=30 or a prognostic burn index (PBI = BI + patient's age) >=100. The survival rate of the patients with BI >=30 was 65.2% with the traditional treatment and 100% with the new guidelines. Likewise, the survival rate of the patients with PBI >=100 was 61.1% with the traditional treatment compared to 100% with the new guidelines. Together, these data demonstrate that the new treatment guidelines dramatically improved the treatment outcome and survival of SEB patients. PMID- 27279805 TI - Response of keloid fibroblasts to Vitamin D3 and quercetin treatment - in vitro study. AB - Keloid scars continue to pose a challenge to clinicians as the treatment armamentarium lacks a formidable agent to tackle them. We have undertaken an in vitro study based on the mechanism of action of Vitamin D3 and quercetin on isolated keloid fibroblasts. Dose-dependent action on the reduction of cellular proliferation, collagen synthesis and induction of apoptosis by Vitamin D3 and quercetin are analyzed and probable mechanism of action is elaborated. This study thus opens up newer avenues in tackling keloid scars effectively. PMID- 27279806 TI - [Not Available]. AB - Use of local/regional anesthesia in burn patients is limited by many factors. It is considered as marginal in the multimodal treatment of nociceptive pain. We conducted a retrospective study on regional anesthesia used for analgesia over a period of three years. Given the lack of available literature on this subject, the results obtained from this study will enable suggestions to be made for possible uses of this technique. We identified 634 uses of regional anesthesia of which 96% were in adults. Most cases involved the lower limbs (76%). Spinal anesthesia was performed on 32 patients, including four children. Incidents were infrequent (3%) and had no morbid consequence. Regional anesthesia may be a useful option in a multimodal strategy of analgesia, allowing early passive rehabilitation and recovery after surgical skin grafts. It should be assessed in outpatients, since 95% of burns patients are not hospitalized. Use of regional anesthesia in burn patients should generate more interest to allow the establishment of protocols in multidisciplinary reflection. PMID- 27279807 TI - [Not Available]. AB - The early management of pediatric hand burns includes surgical treatment, medical follow up and prevention of abnormal scarring by splits and/or pressure garment therapy. The aim of this review was to find the best available evidence in the literature on the surgical part of this management. This review started with a search in the PubMed database for the keywords, hand AND/OR child AND/OR burn. Only the articles published between January 1(st), 2005 and January 1(st), 2011 were selected. The data were compared to French and American textbooks. Contradictory findings were reported on the timing of the excision and graft, with only two comparative studies reported, with a lot of biases. The state of the art on the initial management of hand burns in children is not totally conclusive due to the lack of statistic power in these studies, but many expert opinions help to define options for good therapeutic paradigms. It is important to include these patients in prospective protocols with both early and long-term follow-up in order to increase the amount of evidence at our disposal. PMID- 27279808 TI - Surgical treatment of burns sequelae. our experience in the Department of Plastic and Reconstructive Surgery, Pristina, Kosovo. AB - Burn injuries are very frequent in Kosovo, leading to long-lasting physical, functional, aesthetic, psychological and social consequences directly proportional to the time of healing; the longer it takes for the burn wound to heal, the more serious are the sequelae. The objectives of the present study are to review the epidemiological, clinical and therapeutic aspects of burn patients presenting with post-burn sequelae and treated at the Department of Plastic and Reconstructive Surgery, Pristina, Kosovo, from January 2005 until December 2011. This study included 188 patients with burns sequelae. The following variables were considered: age, sex, anatomical location, pathological types, and surgical procedure. There were 82 men (43.6%) and 106 women (56.4%), ranging in age from 0 to 67 years (mean age 33.5 years), most of the patients were children (139 = 73.9%). Burn contractures were observed in 135 (71.8%) patients, hypertrophic scars in 32 (17%), keloids in 10 (5.3%), alopecia in 6 (3.2%), syndactyly in 12 (6.4%), ectropion in 4 (2.1%) and ear deformity in 1 (0.53%) cases. To correct the deformities the most common choice was the Z-plasty technique, used in 31.4% of cases, followed by Z-plasty+full thickness skin grafts in 21.8%, full thickness skin grafts in 18.1%, tissue expansion in 8%, Z-plasty+local flaps in 4.8%, flaps (local, fascio-cutaneous, radial forearm) in 6.9% and direct closure in 6.4%. Timely wound closure and the development of an individual programme for surgical treatment of burns sequelae are crucial for optimal outcomes in patients with burns. PMID- 27279809 TI - Tissue expanders in post-burn alopecia: with or without galeotomies? AB - The tissue expansion technique is part of the reconstructive surgeon's armamentarium. It provides donor skin that is an optimal match in terms of skin colour, texture, sensation and hair-bearing characteristics. Tissue expansion of the scalp is one of the methods used for the management of alopecia. This method allows the expansion of normal hair-bearing scalp to cover the area of alopecia. Unfortunately, the tough galeal layer prevents easy and fast expansion of the scalp and increases the rate of expander extrusion. A prospective and retrospective comparative analysis of the use of subgaleal expanders with or without galeotomies to manage post-burn alopecia was conducted in the Burn Unit of the Menofia University Hospital, in the period from September 2010 to November 2014. Thirty expanders in 30 patients with alopecia were included in the study. These constitute the experience of a single surgeon. Twenty expanders were applied to the subgaleal plane without galeotomies and 10 were applied with galeotomies. Indications for scalp expansion were mainly post-burn alopecia and scarring. Complications and failures were recorded. Adding galeotomies to subgaleal tissue expander placement for scalp alopecia decreases the time of expansion, allows a larger amount of fluid to be injected each time without inducing pain, and decreases the rate of expander extrusion. Adding galeotomies to subgaleal tissue expander placement for post-burn alopecia ensures preservation of galeal blood supply for easier and faster expansion of the scalp and fewer expander extrusion complications. PMID- 27279810 TI - The cost of post-burn scarring. AB - Deep burns lead to scarring and contractures for which there is little or no published data on treatment costs. The purpose of this study was to fill this gap by analysing treatment costs for burn sequelae. To do this, German-DRG for in patient treatment was collected from the Burn Centre Lower Saxony. DRG-related T95.-coding served as a tool for burn-associated sequelae. Data on scar occurrence, plastic-reconstructive surgery and sick leave were collected by a questionnaire. The findings showed that 44.6% patients reported post-burn scarring and 31% needed surgical intervention. The expected risk for readmission was significantly higher (p=0.0002) with scars compared to without. Significantly higher costs for pressure garments were noted for scarred patients (p=0.04). No differences were found for ointments, silicone dressings or pain medication. Treatment costs for patients with scars were 5.6 times higher compared with no scar assessed by G-DRG. No differences were stated subsuming multiple readmissions for post-burn treatment per individual. Significantly higher costs (p=0.03) were noted for patients with burn sequelae other than scars with regard to individual readmissions. It has been revealed that treatment of scars causes higher costs than for other burn sequelae because of multiple surgical interventions. To reduce post-burn scarring and costs, specialized burn centres provide optimal and state-of-the-art treatment. As well as this, more emphasis should be laid on promoting research for the development of novel anti-scarring therapies. PMID- 27279811 TI - Is a self-inflicted burn part of a repeated self-harm pattern? AB - Self-inflicted burns (SIB) consistently account for a small proportion of burn injuries. There is a wide spectrum of SIB, from minor burns through to major life threatening burn injuries in suicidal patients who have committed self immolation. Non-fatal deliberate self-harm (DSH) is a common reason for presenting to hospital. This occurs in many forms including wounding, burning and poisoning to name a few. Such behaviours are commonly repeated, sometimes with increasing severity. DSH is a major risk factor for subsequent suicide. We had observed patterns of repeated self harm behaviours in patients presenting to our centre with SIB. Patterns of repeated DSH in those presenting with self-inflicted burns have not previously been described in the literature. In a five-year period (2008 to 2012) 84 patients presented to our burns centre with SIB. Within this population, 39 patients (46%) were identified on a national database as having been admitted to an acute National Health Service (NHS) trust somewhere in the UK with sequelae of deliberate self-harm. There had been a total of 128 additional hospital admissions. In the majority of cases (85%) another admission preceded the presentation to our service with SIB. Only four out of the 17 SIB patients (24%) who died of their injuries had previous hospital admissions with DSH. This lends weight to the need for thorough holistic assessment of any patient admitted to hospital with sequelae of deliberate self-harm in order to try and provide appropriate support and interventions for these vulnerable individuals to prevent recurrent self-harm or suicide. PMID- 27279813 TI - Fires in history: the cathar heresy, the inquisition and brulology. PMID- 27279812 TI - How fast can a naturopathic medicine cause skin burn? a case report of garlic burn. AB - This paper presents a case in which a chemical burn resulted from the use of garlic as a naturopathic medicine for knee pain. PMID- 27279814 TI - The EVER genes - the genetic etiology of carcinogenesis in epidermodysplasia verruciformis and a possible role in non-epidermodysplasia verruciformis patients. AB - In recent years, the two adjacent novel EVER1 and EVER2 genes have been identified, whose mutations are responsible for the development of epidermodysplasia verruciformis (EV). Epidermodysplasia verruciformis is a rare, autosomal recessive genodermatosis associated with increased risk of skin carcinoma. Up to now 7 mutations in the EVER1 gene and 5 mutations in the EVER2 gene have been identified only in EV. It was also determined that the EVER genes belong to a novel gene family, the transmembrane channel-like (TMC) family, and are responsible for properly functioning zinc homeostasis. These observations have given new insights into EV pathogenesis. PMID- 27279815 TI - Significance of diet in treated and untreated acne vulgaris. AB - The relationship between diet and acne is highly controversial. Several studies during the last decade have led dermatologists to reflect on a potential link between diet and acne. This article presents the latest findings on a potential impact that diet can have on pathogenesis of acne vulgaris. The association between diet and acne can no longer be dismissed. Compelling evidence shows that high glycemic load diets may exacerbate acne. Dairy ingestion appears to be weakly associated with acne and the roles of omega-3 fatty acids, dietary fiber, antioxidants, vitamin A, zinc and iodine remain to be elucidated. The question of what the impact of diet is on the course of acne vulgaris still remains unclear. PMID- 27279816 TI - Diagnostic significance of nitric oxide concentrations in exhaled air from the airways in allergic rhinitis patients. AB - INTRODUCTION: The effect of nitric oxide (NO) on the human body is very important due its physiological regulation of the following functions of airways: modulation of ciliary movement and maintenance of sterility in sinuses. AIM: To evaluate the diagnostic significance of NO concentrations in exhaled air from the upper and lower airways in patients diagnosed with allergic rhinitis (AR). MATERIAL AND METHODS: The subjects included in the study were a group of 30 people diagnosed with sensitivity to environmental allergens and a control group consisting of 30 healthy subjects. The measurement of NO in the air exhaled from the lower and upper airways was performed using an on-line method by means of Restricted Exhaled Breath (REB), as well as using the measurement procedure (chemiluminescence) set out in the guidelines prepared in 2005 by the American Thoracic Society and the European Respiratory Society. RESULTS: In the late phase of the allergic reaction, higher values of the level of exhaled NO concentration from the lower airways were observed in the groups of subjects up to the threshold values of 25.17 ppb in the group of subjects with year-round allergic rhinitis and 21.78 ppb in the group with diagnosed seasonal allergic rhinitis. The difference in the concentration of NO exhaled from the lungs between the test group and the control group in the 4(th) h of the test was statistically significant (p = 0.045). CONCLUSIONS: Exhaled NO should be considered as a marker of airway inflammation. It plays an important role in the differential diagnosis of allergy. PMID- 27279817 TI - Selected CC and CXC chemokines in children with atopic asthma. AB - INTRODUCTION: There are only limited data on CC and CXC chemokines regulation in children with asthma. AIM: We compared the serum profile of selected CC and CXC chemokines in patients with atopic asthma and healthy children. MATERIAL AND METHODS: Serum concentration of CC chemokines RANTES, MCP-1, and CXC chemokines IP-10, MIG, IL-8, RANTES was measured using cytometric bead array in 44 children with atopic asthma and 17 healthy subjects. RESULTS: The concentration of RANTES was significantly higher and the MIG level was lower in all children with asthma as compared to their control counterparts. We observed increased RANTES and decreased MIG levels also in patients with stable asthma when compared with children in the control group. The IP-10 concentration was similar between the whole asthma group and healthy controls, while significantly increased levels of this chemokine in acute asthma have been observed when compared to stable asthma. For MCP-1 and IL-8, the serum concentration was similar in all compared groups. The MIG concentration correlated positively with IP-10, IL-8, and CRP levels and negatively with the eosinophil count. A negative correlation between the IP-10 and eosinophil count and a negative correlation between FEV1 and IP-10 were found. CONCLUSIONS: An increased serum RANTES level in children with asthma may result in enhancement of Th2 lymphocyte recruitment into the airway. A decreased expression of Th1 chemokine MIG in children with stable asthma may contribute to a diminished antagonizing effect on Th2 cytokine production and hence intensify Th2 predominance. An increased IP-10 level in children during an asthma attack suggest that this chemokine is a serological marker of disease exacerbation. PMID- 27279818 TI - Quality of life and severity of skin changes in the dynamics of psoriasis. AB - INTRODUCTION: Psoriasis is a chronic skin disease with periods of recurrence and remission. The skin changes which are typical of this disease can have a considerable effect on the patient's psychological state, self-esteem and body image. It can also affect the patient's functioning in all areas of life and quality of life. AIM: The present study characterized the patient needs to improve the quality of life in specified areas in patients depending on the severity of psoriatic changes. MATERIAL AND METHODS: The study was conducted in two stages on 100 patients aged from 18 to 66. A dermatological examination was conducted in stage one. Patients' dermatological condition was assessed with the Psoriasis Area and Severity Index (PASI). Clinical and socio-economic information was collected in stage two using a questionnaire, a medical interview and a standardized questionnaire measuring quality of life, the WHOQOL-BREF. RESULTS: The following factors had the greatest effect on the general quality of life and quality of health ratings in the studied sample: severity of psoriatic changes, duration of the most recent recurrence and sex. Severity of psoriatic changes had a negative effect on the patient's somatic, psychological, environmental and social functioning. Duration of the most recent recurrence had a negative effect on social functioning. Practical implications of this study allow dermatologists to determine the appropriate therapeutic intervention which improves the quality of life of these patients on the one hand, and will increase patient's involvement in the process of treatment on the other hand. CONCLUSIONS: Quality of life is more impaired by more severe chronic skin disease. PMID- 27279819 TI - Food allergy is associated with recurrent respiratory tract infections during childhood. AB - INTRODUCTION: To find out whether children with food allergy have an increased risk of recurrent upper and lower respiratory tract infections and of asthma. AIM: To describe the clinical profile of children diagnosed with food allergy referred to the Allergy Clinic. MATERIAL AND METHODS: We conducted a retrospective study to assess the patients' demographic, anthropometric and clinical data. The analysis included data of all children by the age of 10 years (registered with the Allergy Clinic between 2012 and 2013) in whom IgE mediated food allergy had been diagnosed during 18 months of observation. RESULTS: We included 280 children into the analysis. Recurrent respiratory tract infections (rRTI), asthma and gastrointestinal (GI) symptoms were observed in 153 (54.6%), 96 (34.3%), 39 (13.9%), respectively, with a significant increasing trend across age-subgroups. In children from 1 to 2 years old, sensitization to beta lactoglobulin increased the risk of rRTI (OR = 3.91; 95% CI: 1.03-14.87). In older children sensitization to allergens other than milk or egg decreases the risk of rRTI (OR = 0.25; 95% CI: 0.10-0.62); sensitization to egg decreased the risk of asthma diagnosis (OR = 0.09; 95% CI: 0.01-0.75). We did not identify food allergens which change the risk of GI symptoms in children. This finding was consistent throughout all age-subgroups. CONCLUSIONS: Sensitization to beta lactoglobulin increased the risk of rRTI in children under 2 years of age nearly four times. The presence of sensitization to food allergens above 3 years of age did not increase the risk of developing clinical presentation of food allergy other than atopic dermatitis. PMID- 27279820 TI - Presence of selected metabolic syndrome components in patients with psoriasis vulgaris. AB - INTRODUCTION: Recent studies have suggested a strong association between psoriasis and obesity, dyslipidemia, hypertension, resistance to insulin and metabolic syndrome. AIM: To assess the prevalence of selected metabolic syndrome components in patients with psoriasis and the effect of the abnormalities on the disease activity. MATERIAL AND METHODS: Two hundred and forty-six patients diagnosed with psoriasis and 75 healthy individuals as controls were included in the study. Psoriasis activity was evaluated by the Psoriasis Area and Severity Index (PASI). RESULTS: There was a statistically significant difference in triglyceride concentration between psoriasis patients and controls (p = 0.00001), which was not found for high-density lipoprotein (HDL) concentration. Mean values of serum glucose level in patients with psoriasis were significantly higher than in controls (p = 0.046). Further statistical analysis of the obtained results showed significantly higher systolic blood pressure in the psoriasis patients than in the controls (p = 0.0001), but there was no statistically significant difference in diastolic blood pressure between the investigated groups (p > 0.05). CONCLUSIONS: Higher prevalence of metabolic syndrome components was observed in patients with psoriasis than in the general population. PMID- 27279821 TI - Differentiating of cross-reactions in patients with latex allergy with the use of ISAC test. AB - INTRODUCTION: Differentiating between cross-reactivity and double sensitization is still a challenging issue in allergology. AIM: To differentiate cross reactions accompanying latex allergy with the use of the ISAC test. MATERIAL AND METHODS: Thirty-nine patients reporting immediate allergic reactions to latex were enrolled into the study (group A). The control group was comprised of 41 patients with allergic diseases not associated with latex (group B) and 20 healthy individuals (group C). Their history was recorded and skin prick tests were performed with latex, airborne and food allergens. Specific IgE against food allergens, latex (k82) and recombined latex allergens were determined. ImmunoCAP ISAC test was performed with 103 molecules. RESULTS: Sensitization to latex was found by means of skin tests in 16 cases and sIgE against latex was revealed in 12 cases (including 10 positive in both SPT and sIgE). In the ISAC test antibodies against recombined latex allergens were found in 8 patients with rHev b 6 as the most common. All the patients positive for rHev b 1, 5, 6, 8 had allergy or asymptomatic sensitization to food allergens cross-reacting with latex. Some reactions could not have been differentiated due to the lack of allergens in the ISAC test. Others, not related to latex-fruits syndrome were explained by cross-reactivity with other profilins or PR-10 proteins. CONCLUSIONS: ImmunoCAP ISAC test could be useful in differentiating between cross reactions and double sensitizations. However, in the case of latex its advantages are limited due to a small panel of allergens. PMID- 27279822 TI - The prevalence of mutations in the gene encoding filaggrin in the population of Polish patients with atopic dermatitis. AB - INTRODUCTION: The genetic background of atopic dermatitis (AD) is complex, involves many genes and their participation varies in varied populations, and depends on the intensity and course of a disease. Changes in the nucleotide sequence of the FLG gene and a reduced number or a deficit of the functional product of processed profilaggrin can be one of risk factors for atopic dermatitis. AIM: To determine the prevalence of R501X and 2282del4 mutations of the FLG gene in patients with AD. MATERIAL AND METHODS: The studied group included 60 patients with clinically diagnosed AD, and the control group included 61 healthy volunteers. The study protocol included collection of biological material for tests, DNA isolation and evaluation of its quality and quantity, and PCR amplification of the isolated genetic material. RESULTS: In the studied group, both changes in the nucleotide sequence of the FLG gene were detected and in the control group no tested mutations were detected. In 18 (30%) patients with AD, 22 mutations (4 heterozygous and 1 homozygous ones of R501X and 10 heterozygous and 7 homozygous ones of 2282del4) were detected. CONCLUSIONS: A high rate of mutations of the FLG gene in patients with clinically diagnosed AD and pathologically dry skin was observed in the studied population. The 2282del4 mutation occurred more often than R501X. PMID- 27279823 TI - Analysis of the quality of life of patients with asthma and allergic rhinitis after immunotherapy. AB - AIM: To assess the quality of life of Polish patients with asthma and/or allergic rhinitis before the implementation and after 30-36 months of immunotherapy. MATERIAL AND METHODS: Two hundred patients have been involved in the study: 101 with allergic asthma and 99 with pollinosis. In order to collect research material, the Polish versions of AQLQ (Asthma Quality of Life) and RQLQ (Rhinoconjunctivitis Quality of Life) questionnaires have been used. The self administered questionnaires concerned such data as age, sex and the patients' subjective evaluation of their quality of life. RESULTS: The average increase in quality of life of patients with asthma was 0.84 and of patients with allergic rhinitis - 1.50. A hypothesis was made that changes of quality of life in each examined group differed significantly. A test for two fractions showed that for patients with asthma it was 7.74 and for patients with allergic rhinitis - 10.38. A statistical analysis showed no such relation in the group of patients with asthma (coefficient of correlation = 0.08) and a slight correlation in the group of patients with allergic rhinitis (coefficient of correlation = 0.20). Applied tests did not show any significant differences, which means that an average increase in quality of life does not depend on sex and age of both examined groups. CONCLUSIONS: On the basis of the research conducted among patients before and after a 3-year period of immunotherapy, the following conclusions have been drawn: 1) immunotherapy significantly improves the objective quality of life in both groups; 2) a slight correlation has been identified between the objective and subjective dimension of quality of life amongst patients with asthma, what contributes to a better quality of life; 3) in both study groups, no significant relationship between gender or age and improvement in quality of life has been noted; 4) immunotherapy, from the point of view of the improvement of quality of life, is a valuable therapeutic tool in patients with atopic bronchial asthma and allergic rhinitis. PMID- 27279824 TI - Carcinoma en cuirasse as an initial manifestation of inflammatory breast cancer. PMID- 27279825 TI - Bowenoid papulosis in a linear distribution. PMID- 27279827 TI - Subcutaneous fat necrosis in neonates after therapeutic hypothermia - report of two cases. PMID- 27279826 TI - Iatrogenic Kaposi's sarcoma following therapy for rheumatoid arthritis. PMID- 27279828 TI - A case of lipoatrophic panniculitis in a 2-year-old boy. PMID- 27279829 TI - Paths to the discovery of antivenom serotherapy in France. AB - The current study presents a descriptive chronological survey of the articles published by Cesaire Auguste Phisalix and Albert Calmette on snake poison, with the aim of shedding a light on the areas of research and reasoning followed by these scientists, leading up to their simultaneous discovery of antivenom serotherapy in 1894. The path taken by Phisalix is revealed in 15 articles that demonstrate the motivation of a naturalist and the way he confronted the puzzle of immunity against snake venom. In the case of Calmette, two articles preceded the discovery; microbiology was his theoretical base and the Pasteurian spirit of solving health problems his driving force. These two researchers followed distinct paths, mobilized by different motivations, but produced one single result. It is incontestable that the discovery of antivenom serotherapy was the work of two groups of researchers who deserve equal recognition, but who, in fact, did not receive it. Following the discovery both Calmette and Phisalix returned to their previous motivations. Calmette put the discovery into practice and began to produce antivenom serum in Lille. He came to be generally considered as the sole discoverer of antivenom serotherapy and was the recipient of a number of prestigious prizes. Phisalix, on the other hand, received little recognition and returned to his original interests, devoting himself to research on natural immunity. In Brazil, the discovery of antivenom serum therapy had a profound impact on the work of Vital Brazil Mineiro da Campanha, a researcher known worldwide for his scientific discoveries and for the evidence of the specificity of antivenom serums. PMID- 27279830 TI - Stata Modules for Calculating Novel Predictive Performance Indices for Logistic Models. AB - BACKGROUND: Prediction is a fundamental part of prevention of cardiovascular diseases (CVD). The development of prediction algorithms based on the multivariate regression models loomed several decades ago. Parallel with predictive models development, biomarker researches emerged in an impressively great scale. The key question is how best to assess and quantify the improvement in risk prediction offered by new biomarkers or more basically how to assess the performance of a risk prediction model. Discrimination, calibration, and added predictive value have been recently suggested to be used while comparing the predictive performances of the predictive models' with and without novel biomarkers. OBJECTIVES: Lack of user-friendly statistical software has restricted implementation of novel model assessment methods while examining novel biomarkers. We intended, thus, to develop a user-friendly software that could be used by researchers with few programming skills. MATERIALS AND METHODS: We have written a Stata command that is intended to help researchers obtain cut point free and cut point-based net reclassification improvement index and (NRI) and relative and absolute Integrated discriminatory improvement index (IDI) for logistic-based regression analyses.We applied the commands to a real data on women participating the Tehran lipid and glucose study (TLGS) to examine if information of a family history of premature CVD, waist circumference, and fasting plasma glucose can improve predictive performance of the Framingham's "general CVD risk" algorithm. RESULTS: The command is addpred for logistic regression models. CONCLUSIONS: The Stata package provided herein can encourage the use of novel methods in examining predictive capacity of ever-emerging plethora of novel biomarkers. PMID- 27279831 TI - Ramadan Fasting Decreases Body Fat but Not Protein Mass. AB - BACKGROUND: Many studies have shown various results regarding the effects of Ramadan fasting on weight and body composition in healthy individuals. OBJECTIVES: This study aimed to evaluate the effect of Ramadan fasting on body composition in healthy Indonesian medical staff. OBJECTIVES: In this study, we examined the influence of Ramadan fasting on body composition in healthy medical staff. PATIENTS AND METHODS: The longitudinal study was performed during and after Ramadan fasting in 2013 (August to October). Fourty-three medical staff members (physicians, nurses and nutritionists) at the Internal Medicine Ward of the Dr. Cipto Mangunkusumo General Hospital were measured to compare their calorie intake, weight, body mass index, waist-to-hip ratio (WHR), and body composition, including body fat, protein, minerals and water, on the first and 28(th) days of Ramadan and also 4-5 weeks after Ramadan fasting. Measurements were obtained for all 43 subjects on the 28(th) day of Ramadan, but they were obtained for only 25 subjects 4 - 5 weeks after Ramadan. RESULTS: By the 28(th) day of Ramadan, it was found that the body weight, BMI, body fat, water and mineral measures had decreased significantly (-0.874 +/- 0.859 kg, P < 0.001; 0.36 +/- 0.371 kg/m(2), P < 0.001; -0.484 +/- 0.597 kg, P < 0.001; -0.293 +/- 0.486 kg, P = 0.001; -0.054 +/- 0.059 kg, P < 0.001, respectively). Protein body mass and calorie intake did not significantly change (-0.049 +/- 0.170 kg, P = 0.561; 12.94 +/- 760.608 Kcal, P = 0.082 respectively). By 4 - 5 weeks after Ramadan, body weight and composition had returned to the same levels as on the first day of Ramadan. CONCLUSIONS: Ramadan fasting resulted in weight loss even it was only a temporary effect, as the weight was quickly regained within one month after fasting. The catabolism catabolic state, which is related to protein loss, was not triggered during Ramadan fasting. Further research is needed to evaluate the effects of weight loss during Ramadan fasting in healthy individuals. PMID- 27279832 TI - Leptin Resistance: A Possible Interface Between Obesity and Pulmonary-Related Disorders. AB - CONTEXT: Under normal physiological conditions, leptin regulates body weight by creating a balance between food intake and energy expenditure. However, in obesity, serum leptin levels increase and become defective to retain energy balance. EVIDENCE ACQUISITION: Elevated serum leptin levels are regarded as an established marker of obesity. It is also reported that obese asthmatic patients have maximum serum leptin levels compared to other groups such as non-obese asthmatics, and normal obese and non obese subjects without asthma. In addition to having an appetite suppressing effect, leptin also regulates certain acute phase protein expressions including alpha-1 antitrypsin (A1AT) in the liver. RESULTS: A1AT is a protease inhibitor that counterbalances the activity of the neutrophil elastase (NE) enzyme. A1AT reductions in obese-leptin resistant subjects lead to increased NE activity. The overactivity of NE degrades lung tissue proteins, which may lead to pulmonary disorders including asthma. CONCLUSIONS: On the basis of prior studies, it could be hypothesized that, in obese asthmatic patients, the highest degree of leptin failure/resistance might lead to the creation of an imbalance between NE and its inhibitor A1AT. To ascertain this, large scale prospective studies are warranted to assess the comparative serum leptin and A1AT levels and NE activity in asthmatic non-obese and obese patients, simultaneously. Such studies might help to devise novel interventional therapies for the treatment of pulmonary-related problems including asthma, chronic obstructive pulmonary disorder (COPD), and other lung defects in susceptible obese subjects in the future. PMID- 27279833 TI - Thyroid and Pregnancy in Tehran, Iran: Objectives and Study Protocol. AB - BACKGROUND: Thyroid dysfunction is the second most common endocrine disease in females of reproductive age. There are controversial data on the adverse effect of subclinical thyroid dysfunctions on adverse feto-maternal outcomes. OBJECTIVES: The current study aimed to identify the prevalence of thyroid dysfunction during pregnancy and to assess the effectiveness of treatment with levothyroxine on pregnancy outcomes of females with thyroid autoimmunity with or without subclinical thyroid dysfunction in Tehran, Iran. PATIENTS AND METHODS: The study encompassed two phases: 1) a population based cross sectional study using a cluster sampling method that screened first trimester pregnant females for thyroid disorders, 2) a double-blind randomized clinical trial to determine the effectiveness of levothyroxine on adverse pregnancy outcomes in females with thyroid autoimmunity with or without subclinical thyroid dysfunction. Pregnant females were assessed at their first prenatal visit for serum TSH, T4, T-uptake, TPOAb and urinary iodine following which they were classified as: 1) normal, 2) subclinical TPOAb negative and 3) subclinical/euthyroid TPOAb positive. Females in groups two and three were randomly divided into two groups: group A was treated with levothyroxine (LT4), and group B did not receive any treatment. There was a follow-up program for participants and rates of adverse pregnancy outcomes in the treated and untreated groups were measured. RESULTS: Results of the study provided reliable information regarding the prevalence of thyroid dysfunction among females in Tehran using universal thyroid screening, along with identification of the iodine status of their community. The study aimed to determine whether LT4 treatment exerts beneficial effects in females without overt thyroid dysfunction. PMID- 27279834 TI - Effects of Concentrated Pomegranate Juice on Subclinical Inflammation and Cardiometabolic Risk Factors for Type 2 Diabetes: A Quasi-Experimental Study. AB - BACKGROUND: The health benefits of pomegranate juice have been reported in several studies. However, limited clinical trials have examined the effects of concentrated pomegranate juice (CPJ) on inflammatory factors. OBJECTIVES: This study aimed to investigate the effects of CPJ on metabolic risk factors, including inflammatory biomarkers, in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: In a quasi-experiment trial, 40 type 2 diabetic patients were asked to consume 50 g of CPJ daily for 4 weeks. Anthropometric indices, dietary intake, blood pressure measurements, and fasting blood samples were conducted at baseline and 4 weeks after the intervention. RESULTS: The intake of CPJ produced a significant increase in both total and high-density lipoprotein cholesterol (HDL-C) (4.7% and 3.9%, respectively) from baseline (P < 0.05). However, changes that were observed in serum triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose, and blood pressure were not statistically significant. Administration of CPJ caused significant reduction in serum interleukin-6 (IL-6) (P < 0.05), but tumor necrosis factor-alpha (TNF alpha) and high-sensitivity C-reactive protein (hs-CRP) remained unchanged during the study. The mean value of serum total antioxidant capacity (TAC) was substantially increased (~ 75%) from 381.88 +/- 114.4 at baseline to 1501 +/- 817 after 4 weeks of CPJ consumption. CONCLUSIONS: Consumption of CPJ (50 g/day) appears to have favorable effects on some markers of subclinical inflammation, and to increase plasma concentrations of antioxidants in patients with type 2 diabetes. PMID- 27279835 TI - Effect of JYTK on Antioxidant Status and Inflammation in Patients With Type 2 Diabetes: A Randomized Double-Blind Clinical Trial. AB - BACKGROUND: Diabetes is a metabolic disorder caused by oxidative stress and inflammation. JianYuTangKang (JYTK), as a potential Chinese integrative medicine, is an antioxidant used in Chinese medicine with potential anti-inflammatory properties. OBJECTIVES: The present randomized clinical trial was carried out to evaluate the effects of JYTK on oxidative stress and inflammation in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: The parallel, randomized, double-blinded, placebo-controlled clinical trial included 150 newly diagnosed T2DM patients receiving metformin treatment (1.5 g/day), some of whom also received JYTK (4.5 g/day) in tablet form. The control group received 4.5 g/day placebo plus 1.5 g/day metformin. Body mass index (BMI), fasting plasma glucose, urinary albumin-to-creatinine ratio, and complete blood count as well as antioxidant and inflammation indices such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GPX), and high sensitivity C-reactive protein (hs-CRP) levels were assessed at baseline and at different time points during the treatment. RESULTS: All 112 patients, including 59 in the treatment group (JYTK + metformin) and 52 controls (metformin only) completed the 26-week clinical trial. JYKT plus metformin treatment increased IL-6 (36.4 +/- 11.5 ng/L; P < 0.05), TNF-alpha (17.5 +/- 11.3 vs. 22.5 +/- 12.9 ng/L; P < 0.05), and MDA (1.9 +/- 0.9; P < 0.05) levels compared to the control (2.2 +/- 0.6 mM/mL), whereas total SOD level decreased (98.1 +/- 30.4 vs. 78.5 +/- 29.3 U/mL; P < 0.05). There were no changes in GPX and hs-CRP levels. There were no adverse effects associated with JYTK treatment. CONCLUSIONS: JYTK combined with metformin improves some antioxidant indices (SOD and MDA), and decreases inflammation in patients with T2DM, suggesting that it can reduce the risk of diabetic complications. PMID- 27279836 TI - miR-630 functions as a tumor oncogene in renal cell carcinoma. AB - INTRODUCTION: MicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cell processes during cancer progression. Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. In this study, we aimed to investigate the roles of miR 630 in RCC progression. MATERIAL AND METHODS: Expression of miR-630 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in four renal cancer cell lines (786-O, ACHN, Caki-1, and Caki-2) and one normal human proximal tubule epithelial cell line (HK-2). Next, miR-630 inhibitor was used to inhibit miR-630 expression in 786-O cells. Finally, its effects on cell proliferation, apoptosis, migration, and invasion were evaluated. RESULTS: The expression level of miR-630 was higher in renal cancer cell lines 786-O, ACHN, Caki-1, and Caki-2 than that in the normal renal cell line HK-2 (p < 0.05). Furthermore, a proliferation assay, apoptosis assay, migration assay and invasion assay were performed, and the results showed that down-regulation of miR-630 expression by miR-630 inhibitor significantly inhibited cell proliferation, migration, and invasion, which meanwhile induced cell apoptosis of the renal cancer cell line 786-O. CONCLUSIONS: This is the first time that miR-630 expression has been shown to be associated with renal cancer progression, and down-regulation of miR-630 can inhibit tumor progression, which provides a potential therapeutic target for renal cancer treatment. PMID- 27279837 TI - Analysis of possible genetic risk factors contributing to development of childhood acute lymphoblastic leukaemia in the Latvian population. AB - INTRODUCTION: Childhood acute lymphoblastic leukaemia (ALL) is a complex disease caused by a combination of genetic susceptibility and environmental exposure. Previous genome-wide association studies have reported several single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. Several variations in genes encoding enzymes involved in carcinogenesis are suggested as being associated with an increased risk of ALL development. MATERIAL AND METHODS: We enrolled 77 paediatric ALL patients and 122 healthy controls, and in addition parental DNA was also available for 45 probands. SNPs rs10821936 (ARID5B), rs4132601 (IKZF1), rs2239633 (CEBPE), rs3731217 (CDKN2A) and rs1800566 (NQO1) and the presence of GSTT1 and GSTM1 null variants were detected. For statistical analysis the hybrid method of two designs 'Haplin' was used as well as linkage disequilibrium for family-based association studies. RESULTS: We identified the SNP rs10821936 in the ARID5B gene as being statistically significantly associated with childhood ALL, especially if the C allele is in a homozygous state, relative risk (RR) 4.65, 95% CI: 2.03-10.6, p = 0.0006. Statistically significant differences were not found in other SNPs. We found risk combinations including all five variations, the strongest association being found in a combination where all five genetic variants are in a homozygous state, CCTTTTTTCC, p = 0.032. CONCLUSIONS: The identified SNP rs10821936 could serve as a potential risk marker for childhood ALL development. Further studies in an independent population are needed for verification. PMID- 27279838 TI - Protective effect of hesperidin on oxidative and histological liver damage following carbon tetrachloride administration in Wistar rats. AB - INTRODUCTION: In the current study, the protective effect of hesperidin (HP) on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats was investigated. MATERIAL AND METHODS: Twenty-eight rats were divided equally into four groups. The first group was kept as a control and given only vehicle. In the second, rats were orally administered 50 mg/kg/day HP for 10 days. Carbon tetrachloride was given in a single intraperitoneal injection at the dose of 2 ml/kg in the third group. In the fourth group, the rats were treated with equal doses of CCl4 and HP. RESULTS: It was found that CCl4 induced oxidative stress via a significant increase in the formation of thiobarbituric acid-reactive substances (TBARS) and caused a significant decline in the levels of glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) in rats. In contrast, HP blocked these toxic effects induced by CCl4, causing an increase in GSH, CAT and SOD levels and decreased formation of TBARS (p < 0.01). In addition, histopathological damage increased with CCl4 treatment. In contrast, HP treatment eliminated the effects of CCl4 and stimulated anti-apoptotic events, as characterized by reduced caspase 3 activation. CONCLUSIONS: The current study demonstrated that CCl4-induced hepatotoxicity can be prevented with HP treatment. Thus, co-administration of HP with CCl4 may be useful for attenuating the negative effects of CCl4 on the liver. PMID- 27279839 TI - Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits. AB - INTRODUCTION: Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits. MATERIAL AND METHODS: The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP 2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment. RESULTS: It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups. CONCLUSIONS: The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits. PMID- 27279840 TI - Regulation of expression level of fms-like tyrosine kinase-4 is related to osteoclast differentiation. AB - INTRODUCTION: The aim of this study is to determine whether regulation of the expression level of fms-like tyrosine kinase-4 (Flt-4) is related to osteoclast differentiation. MATERIAL AND METHODS: Osteoclast formation and differentiation of mouse bone marrow cells and RAW264.7 cells were performed. To induce osteoclast differentiation, RANKL (50 ng/ml) with or without vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor-D (VEGF-D) was added to mouse bone marrow cells and RAW264.7 cells. Then cells were examined under a microscope. TRAP-positive cells with 3 nuclei or more were considered as osteoclasts and counted. The Flt-4 gene was knocked down by transfection of siRNAs against Flt-4. Immunoblot analyses were performed. RESULTS: The osteoclast formation assay indicated that VEGF-C resulted in 500 or 450 vs. 100 (p < 0.05) of osteoclasts in mouse bone marrow cells and RAW264.7 cells, respectively. Vascular endothelial growth factor-D resulted in about 600 or 630 vs. 100 (p < 0.05) of osteoclasts for both mouse bone marrow cells and RAW264.7 cells. The knock-down of Flt-4 expression abolished the induction by VEGF-C or VEGF-D, resulting in induction similar to that of the negative control PBS. CONCLUSIONS: Both VEGF-C and VEGF-D can induce osteoclast differentiation in the presence of the receptor activator of nuclear factor kappaB ligand. Down-regulation of expression level of Flt-4 protein abolishes osteoclast differentiation induced by VEGF-C or VEGF-D. PMID- 27279841 TI - Lipid-lowering and anti-inflammatory effects of omega 3 ethyl esters and krill oil: a randomized, cross-over, clinical trial. AB - INTRODUCTION: Polyunsaturated fatty acids (PUFAs) derived from different sources could have different lipid-lowering effects in humans. The main aim of our study was to compare the short-term triglyceride-lowering efficacy of krill oil and purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects. MATERIAL AND METHODS: This double-blind, randomized clinical trial was carried out in 25 moderately hypertriglyceridemic subjects (TG = 150-500 mg/dl). After a 4-week run-in, participants were allocated to treatment with similar pills containing omega 3 ethyl ester PUFAs 1000 mg twice a day vs. krill oil 500 mg twice a day. After 4 weeks of treatment, participants were asked to observe a 4-week wash-out period, and they were then assigned to the alternative treatment for a further period of 4 weeks. RESULTS: Although both PUFA sources were able to improve TG plasma levels, esterified omega 3 PUFAs were more efficacious than krill oil (p < 0.05). Nonetheless, only krill oil treatment was able to significantly improve high-density lipoprotein cholesterol and apolipoprotein AI levels, compared to both baseline (p < 0.05) and end of treatment with esterified omega 3 PUFAs (p < 0.05) values. Both treatments were able to significantly reduce high-sensitivity C-reactive protein (hs-CRP) levels from the baseline (p < 0.05), but krill oil improved it more efficaciously than esterified omega 3 PUFAs (p < 0.05). CONCLUSIONS: Krill oil has lipid-lowering effects comparable with those obtained through a 4-fold higher dose of purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects, while more efficaciously reducing hs-CRP. PMID- 27279842 TI - Adding carotid total plaque area to the Framingham risk score improves cardiovascular risk classification. AB - INTRODUCTION: Cardiovascular events (CE) due to atherosclerosis are preventable. Identification of high-risk patients helps to focus resources on those most likely to benefit from expensive therapy. Atherosclerosis is not considered for patient risk categorization, even though a fraction of CE are predicted by Framingham risk factors. Our objective was to assess the incremental value of combining total plaque area (TPA) with the Framingham risk score (FramSc) using post-test probability (Ptp) in order to categorize risk in patients without CE and identify those at high risk and requiring intensive treatment. MATERIAL AND METHODS: A descriptive cross-sectional study was performed in the primary care setting in an Argentine population aged 22-90 years without CE. Both FramSc based on body mass index and Ptp-TPA were employed in 2035 patients for risk stratification and the resulting reclassification was compared. Total plaque area was measured with a high-resolution duplex ultrasound scanner. RESULTS: 57% male, 35% hypertensive, 27% hypercholesterolemia, 14% diabetes. 20.1% were low, 28.5% moderate, and 51.5% high risk. When patients were reclassified, 36% of them changed status; 24.1% migrated to a higher and 13.6% to a lower risk level (kappa index = 0.360, SE kappa = 0.16, p < 0.05, FramSc vs. Ptp-TPA). With this reclassification, 19.3% were low, 18.9% moderate and 61.8% high risk. CONCLUSIONS: Quantification of Ptp-TPA leads to higher risk estimation than FramSc, suggesting that Ptp-TPA may be more sensitive than FramSc as a screening tool. If our observation is confirmed with a prospective study, this reclassification would improve the long-term benefits related to CE prevention. PMID- 27279844 TI - Platelet microparticle number is associated with the extent of myocardial damage in acute myocardial infarction. AB - INTRODUCTION: Activated platelets generate microparticles. Increased platelet microparticles occur in acute myocardial infarction (AMI) and contribute to intracoronary thrombosis and subsequent myocardial injury. This study aimed to investigate the impact of platelet microparticles on intracoronary thrombosis by assessing the relationship between platelet microparticles and the extent of myocardial damage in AMI. MATERIAL AND METHODS: This was a cross sectional study. The subjects were patients with acute coronary syndrome (ACS). Forty-one consecutive subjects with ACS admitted to intensive cardiovascular care unit were enrolled. The clinical spectrum of ACS comprised AMI (n = 26), both ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI), and unstable angina (n = 15). Platelet microparticles were isolated from peripheral venous blood and detected with anti-CD42b-PE by the flow cytometry method. The extent of myocardial damage was determined by measuring the peak level of serial cardiac enzymes within 24 h of admission. RESULTS: Subjects with AMI had a significantly higher number of platelet microparticles than those with unstable angina (4855 +/-4509/ul vs. 2181 +/-1923/ul respectively; p = 0.036). Subjects with STEMI had the highest number of platelet microparticles, but no significant difference was detected as compared to those with NSTEMI (5775 +/-5680/ul vs. 3601 +/-1632/ul). The number of platelet microparticles in AMI was positively associated with the extent of myocardial damage (peak CK-MB: r = 0.408, p = 0.019 and peak GOT: r = 0.384, p = 0.026). CONCLUSIONS: The number of platelet microparticles was increased in AMI as compared to unstable angina and associated with the extent of myocardial damage. PMID- 27279843 TI - Association of free testosterone and sex hormone binding globulin with metabolic syndrome and subclinical atherosclerosis but not blood pressure in hypertensive perimenopausal women. AB - INTRODUCTION: Data on the role of androgens as potential mediators of increasing cardiovascular risk in women at midlife are controversial. The aim of the study was to analyze the relationship of free testosterone (FT) and sex hormone binding globulin (SHBG) with blood pressure and subclinical organ damage and metabolic syndrome (MS) in middle aged hypertensive women. MATERIAL AND METHODS: One hundred and fifty-two women with newly diagnosed arterial hypertension were included in the study. In all subjects blood pressure measurements were performed as well as echocardiographic examination with left ventricular structure and function assessment (GE Vivid 7.0), carotid ultrasound with measurement of intima media thickness (IMT), and carotid-femoral pulse wave velocity (PWV) measurement (Sphygmocor). A fasting blood sample was taken to measure glucose and lipid concentrations. Serum testosterone and SHBG were measured. Free testosterone was calculated according to the Vermeulen formula. Metabolic syndrome was defined following the International Diabetes Federation (IDF) recommendations. RESULTS: Free testosterone was significantly higher and SHBG lower in women with MS independently of menopausal status. The odds ratio of MS per quartile increment in FT after adjustment for covariates was 2.06 (95% CI: 1.16-3.65). There was no correlation between FT, SHBG and blood pressure. Free testosterone was associated with decreased left ventricular diastolic function (E/A ratio beta = -0.19, p = 0.05) and subclinical atherosclerosis (IMT beta = 0.34, p = 0.009), but not arterial stiffness. CONCLUSIONS: Free testosterone and SHBG independently of menopause status are related to MS. Free testosterone is associated with worse metabolic profile, subclinical atherosclerosis and impaired diastolic function of the left ventricle. PMID- 27279846 TI - Increased high-sensitivity C-reactive protein, erythrocyte sedimentation rate and lactic acid in stroke patients with internal carotid artery occlusion. AB - INTRODUCTION: Internal carotid artery occlusion (ICAO) causes high annual rates of mortality and morbidity. It has been established that atherosclerosis is the normal cause of ICAO. As the pathogenesis of atherosclerosis may involve blood lipids, inflammatory factors and other biomarkers, the aim of this study was to assess the changes in these biomarkers and investigate the relationship between these biomarkers and the development of ICAO in stroke patients. MATERIAL AND METHODS: A total of 89 ischaemic stroke inpatients with ICAO (ICAO group) and 89 without ICAO (control group) were studied, retrospectively. The serum was collected from each patient on the 3(rd) day of admission, to measure the lipid parameters and biomarkers, e.g. high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and lactic acid (LA). Histories were taken including age, gender, smoking history, and disease history. Additional analysis was carried out to compare between the genders and evaluate the association between certain biomarkers and ICAO. RESULTS: Among the 89 ICAO cases in this study, the serum levels of hs-CRP, ESR and LA were significantly higher than those in the control group (p <= 0.001). No significant differences were found in the mean levels of total cholesterol, triacylglycerol, HDL cholesterol or glucose, or the known risk factors. Gender also had no influence on these biomarkers. Logistic regression analysis indicated that hs-CRP, ESR and LA were significantly associated with ICAO (p <= 0.05). CONCLUSIONS: These results suggest that hs-CRP, ESR and LA are associated with ICAO in ischaemic stroke patients, but gender has no effect. Therefore, Hs-CRP, ESR and LA may be useful in the early detection of patients with ICAO. PMID- 27279845 TI - Clinical factors associated with early readmission among acutely decompensated heart failure patients. AB - INTRODUCTION: Congestive heart failure (CHF) is a common cause of hospital readmission. MATERIAL AND METHODS: A retrospective study was conducted at Harlem Hospital in New York City. Data were collected for 685 consecutive adult patients admitted for decompensated CHF from March, 2009 to December, 2012. Variables including patient demographics, comorbidities, laboratory studies, and medical therapy were compared between CHF patient admissions resulting in early CHF readmission and not resulting in early CHF readmission. RESULTS: Clinical factors found to be independently significant for early CHF readmission included chronic obstructive pulmonary disease (odds ratio (OR) = 6.4), HIV infection (OR = 3.4), African-American ethnicity (OR = 2.2), systolic heart failure (OR = 1.9), atrial fibrillation (OR = 2.3), renal disease with glomerular filtration rate < 30 ml/min (OR = 2.7), evidence of substance abuse (OR = 1.7), and absence of angiotensin-converting enzyme inhibitors or angiotensin receptor blocker therapy after discharge (OR = 1.8). The ORs were used to develop a scoring system regarding the risk for early readmission. CONCLUSIONS: Identifying patients with clinical factors associated with early CHF readmission after an index hospitalization for CHF using the proposed scoring system would allow for an early CHF readmission risk stratification protocol to target particularly high risk patients. PMID- 27279847 TI - Improvement of survival in Polish stroke patients is related to reduced stroke severity and better control of risk factors: the Krakow Stroke Database. AB - INTRODUCTION: In the last decade, the stroke mortality rate in Poland significantly decreased. We hypothesised that stroke severity, the major determinant of outcome, is lowered in Polish stroke patients. MATERIAL AND METHODS: We compared the stroke severity in two cohorts of first-ever ischaemic stroke patients admitted within 24 h after stroke onset to the Department of Neurology, Jagiellonian University, Krakow in the years 1994-2000 and 2008-2012. To assess stroke severity we used the National Institute of Health Stroke Scale (NIHSS). We defined mild stroke as an NIHSS score <= 4. RESULTS: We included 816 patients hospitalised in the years 1994-2000 and 569 patients hospitalised in the years 2008-2012. NIHSS score on admission was higher in the former (mean: 12.0 +/ 7.0 vs. 8.0 +/-6.0, p < 0.01), and the frequency of mild stroke was higher in the latter (12.7% vs. 41.8%, p < 0.01). Although the frequency of hypertension (67.3% vs. 81.2%, p < 0.01), diabetes mellitus (20.8% vs. 26.4%, p = 0.02) and atrial fibrillation (20.7% vs. 26.2%, p = 0.02) was higher in patients hospitalised in the years 2008-2012, the systolic and diastolic blood pressure values and the frequency of fasting hyperglycaemia were lower in this cohort. This cohort also less frequently suffered from hypercholesterolaemia (25.4% vs. 16.3%, p < 0.01). CONCLUSIONS: Reduced stroke severity is associated with better recognition and control of risk factors and explains the improvement of survival in Polish stroke patients. PMID- 27279848 TI - Cardiovascular diseases in patients 65 years and younger with non-cardiogenic stroke. AB - INTRODUCTION: Approximately 10-15% of patients with stroke are under 65 years of age. The aim of the study was to determine types of stroke In people below 65. We analysed the incidence and types of associated cardiovascular diseases in patients with non-cardiogenic stroke. MATERIAL AND METHODS: In this prospective study patients (aged <= 65) with stroke underwent physical examination, computed tomography of the head, blood tests, electrocardiogram, echocardiography, and transcranial and carotid artery ultrasound. Classification of stroke was performed according to the ASCOD scale. Analysis considered the incidence of heart diseases in patients with non-cardiogenic stroke and the incidence of heart diseases recognised as a cause of cerebral embolism in patients with cardiogenic stroke. RESULTS: The study included 611 patients with stroke at the age of 27-65 (mean: 57.2 +/-6.7; M/F 380/231). Stroke of heterogeneous aetiology was observed in 321 patients, cardiogenic stroke in 78, and stroke caused by small vessel and carotid artery disease in 73 and 72 patients, respectively. The most common heart diseases in non-cardiogenic stroke patients included persistent foramen ovale, coronary heart disease and past myocardial infarction. The most common causes of cardiogenic embolism were cardiomyopathy, atrial fibrillation and interatrial septal defect. CONCLUSIONS: Aetiologically heterogeneous stroke and cardiogenic stroke are the most commonly observed among young stroke patients. Cardiomyopathy and atrial fibrillation are the most common sources of cerebral embolism in young patients with cardiogenic stroke. Nearly 1/5 of patients with a non-cardiogenic stroke have congenital or acquired structural changes in the heart. PMID- 27279849 TI - Clinical evaluation of the AutoPulse automated chest compression device for out of-hospital cardiac arrest in the northern district of Shanghai, China. AB - INTRODUCTION: Whether the AutoPulse automated chest compression device is worthy of clinical use for out-of-hospital cardiac arrest (OHCA) remains controversial. A prospective controlled study was conducted to evaluate the effect of AutoPulse versus manual chest compression for cardiopulmonary resuscitation (CPR) of OHCA patients in the northern district of Shanghai, China. MATERIAL AND METHODS: A total of 133 patients with OHCA who were treated at the Emergency Medical Center of the Tenth People's Hospital Affiliated with Tongji University between March 2011 and March 2012 were included. The patients were randomly assigned to the Manual CPR (n = 64) and AutoPulse CPR groups (n = 69) in accordance with the approach of chest compression received. The primary outcome measure was return of spontaneous circulation (ROSC), and the secondary outcome measures included 24-h survival rate, hospital discharge rate, and neurological prognosis at hospital discharge. RESULTS: The ROSC rate of patients with OHCA was significantly higher in the AutoPulse CPR group than in the Manual CPR group (44.9% vs. 23.4%; p = 0.009). The 24-h survival rate of OHCA patients was significantly higher in the AutoPulse CPR group than in the Manual CPR group (39.1% vs. 21.9%; p = 0.03). The hospital discharge rate of the patients with OHCA was significantly higher in the AutoPulse CPR group than in the Manual CPR group (18.8% vs. 6.3%; p = 0.03). The proportion of patients with OHCA and a cerebral performance category score of 1 or 2 points at hospital discharge was higher in the AutoPulse CPR group than in the Manual CPR group, but the difference was not statistically significant (16.2% vs. 13.4%, p = 1.00). CONCLUSIONS: Use of the AutoPulse increases CPR success and survival rates in patients with OHCA, but its ability to improve cerebral performance requires further evaluation. PMID- 27279850 TI - The relationship between neutrophil-to-lymphocyte ratio and albuminuria in type 2 diabetic patients: a pilot study. AB - INTRODUCTION: Diabetes mellitus (DM) has become a global economic burden due to treatment costs and attendant complications. Albuminuria is the precursor of end stage renal failure and is an inflammatory process. In the recent past, it has been reported that the neutrophil/lymphocyte ratio (NLR), which is a cost effective and accessible marker, may be a favorable indicator of the inflammatory status. The aim of this study was to investigate the relationship between the neutrophil/lymphocyte ratio and the presence and level of diabetic nephropathy (DN). MATERIAL AND METHODS: A total of 112 patients with type-2 DM who were followed by our internal medicine and nephrology clinics between February 2013 and June 2014 were included in this pilot study and were retrospectively evaluated. All participants had a 24-hour urinary albumin excretion (UAE) record. Demographic parameters, biochemical parameters and albuminuria levels were recorded. Patients were divided into three groups according to their level of albuminuria. RESULTS: Significant differences were detected between the groups in terms of NLR (p < 0.001). There was a linear increase in NLR in parallel to the increase in 24-hour UAE mean values (p < 0.001). A positive correlation was detected between NLR and C-reactive protein, urea, creatinine, and red cell distribution width. However, 24-hour UAE was negatively correlated with lymphocyte count (p < 0.001). CONCLUSIONS: A high degree of correlation was determined among albuminuria, glomerular filtration rate and NLR levels. These results may suggest the notion that diabetic nephropathy involves an inflammatory process. PMID- 27279851 TI - Three-dimensional reconstruction and morphological characterization of pituitary macroadenomas. AB - INTRODUCTION: The aim was to investigate the relationship between the tumor (clinicopathologic and radiological) characteristics and the morphological parameters of pituitary macroadenoma or giant adenoma patients using a three dimensional (3D) reconstructed model. MATERIAL AND METHODS: Magnetic resoanance imaging (MRI) was performed preoperatively; tumor grade was determined by the Knosp-Steiner classification and tumor morphology by the SIPAP classification. Pituitary adenomas and adjacent structures were reconstructed three-dimensionally by volume rendering. RESULTS: Fifty-two and 6 patients underwent surgery via the transnasal transsphenoidal or pterional approach, respectively. Knosp-Steiner grades I to IV adenomas were observed in 5.2%, 25.9%, 22.4% and 46.6% of the patients, respectively. The 3D model was reconstructed in all cases with superb delineation of tumor morphology and the spatial relationship between the tumor and adjacent tissues. Pituitary adenomas were categorized into intrasellar (13.8%), suprasellar (20.7%), infrasellar (17.2%), and lobulated adenomas (48.3%). Suprasellar adenomas had the smallest (2.27 +/-3.22 cm(3)) and lobulated adenomas the largest volume (24.61 +/-30.50 cm(3)). Intrasellar adenomas were all functioning, while 75%, 60% and 60.7%, respectively, of suprasellar, infrasellar and lobulated adenomas were nonfunctioning, with a significant association between tumor morphology and secretory function (p = 0.005). CONCLUSIONS: Three dimensional reconstruction of pituitary macroadenomas offers a simplified morphological classification of pituitary adenomas and may be helpful for neurosurgeons to categorize and characterize pituitary adenomas. PMID- 27279852 TI - The safety of intracytoplasmic sperm injection in men with hepatitis B. AB - INTRODUCTION: In this study, we aimed to evaluate the safety of using different sources of sperm when male partners were infected with hepatitis B virus (HBV). MATERIAL AND METHODS: A total of 338 couples receiving their first intracytoplasmic sperm injection (ICSI) cycle at the Department of Reproduction, Ren Ji Hospital, between 2007 and 2012 were enrolled if the female partner tested negative for HBV DNA, HBsAg, HBeAg, HBeAb and HBcAb. Couples were divided into HBV active infection (group B), convalescent infection (group C) and controls (group A). Subgroups were divided by source of sperm: ejaculated sperm and testicular sperm aspiration/percutaneous epididymal sperm aspiration (TESA/PESA) sperm. RESULTS: When using ejaculated sperm for ICSI, two pronuclear (2PN) fertilization rate, implantation rate, clinical pregnant rate, early miscarriage rate and live birth rate showed no significant difference between the three groups. However, in the three TESA/PESA groups, the early miscarriage rate was highest in men with active HBV infection (B2) (23.1%, p = 0.035). The 2PN fertilization rate and CPR were also lower in the active infection group (76.7%, 26.3%) than the convalescent infection (82.9%, 36.2%) and control group (78.2%, 50%), but the difference was not statistically significant. No malformed infant was found in any of these groups. CONCLUSIONS: When men have an active HBV infection, using TESA/PESA sperm may cause lower fertilization, a high miscarriage rate and a lower live birth rate, which indicates that HBV active infection may cause adverse effects on ICSI reproductive performance when using testicular or epididymal aspirated sperm. PMID- 27279853 TI - The effect of small intestinal bacterial overgrowth on minimal hepatic encephalopathy in patients with cirrhosis. AB - INTRODUCTION: The aim of the study was to investigate the significance of factors associated with minimal hepatic encephalopathy (MHE) in cirrhotic patients. MATERIAL AND METHODS: Between September 2012 and August 2013, 60 cirrhotic patients, including MHE and non-MHE (NMHE) patients, were included in the study. Associated factors and clinical factors were analyzed to see if they were significantly different between MHE and non-MHE patients. Upon identifying the factors showing differences, we applied multivariate regression analysis to further decide which were the most significant ones to differentiate MHE from NMHE patients. RESULTS: There were 26 patients diagnosed with MHE and 34 with NMHE. Our results demonstrated that the prevalence rate of small intestinal bacterial overgrowth (SIBO) was highly associated with patients with MHE (65.4%, 17 out of 26), in contrast to the rate in NMHE patients (8.8%, 3 out of 34). We also found that factors including age, education level, intelligent test results, plasma albumin level and plasma ammonia levels were significantly different between MHE and NMHE patients. Ultimately, with logistic regression analysis, we found that SIBO was the most significant factor differentiating MHE patients from NMHE patients (p < 0.05). CONCLUSIONS: In cirrhotic patients, SIBO was highly associated with MHE. This may further our understanding of the mechanisms of MHE and help to develop potential therapeutic interventions to treat cirrhotic patients with MHE. PMID- 27279854 TI - Endometrial study in patients with postmenopausal metrorrhagia. AB - INTRODUCTION: The aim of the study was to devise a strategy to diagnose malign endometrial pathologies (adenocarcinoma or atypical hyperplasia) that minimizes the number of invasive tests done (hysteroscopy, aspiration biopsy or curettage) with no loss of its detection efficiency. MATERIAL AND METHODS: We retrospectively studied the clinical histories of 779 postmenopausal women at the University Hospital Complex of Albacete, for whom an endometrial study had been done (hysteroscopy, aspiration biopsy or curettage) with a 1-year follow-up between 1 March 2006 and 31 March 2008. RESULTS: There were 77 cases of a malignant pathology (66 adenocarcinomas and 11 hyperplasias with atypia); 96.1% had metrorrhagia, and there were only 3 cases of asymptomatic patients (all 3 presented endometrial thickness of > 5 mm: 10, 12 and 15 mm). The sensitivity and specificity of the transvaginal ultrasound, with a 5 mm cut-off point to diagnose a malignant pathology, were 98.4% and 30.1%, respectively; 89.1% and 99.6%, respectively, for aspiration biopsy; 83.9% and 99.1%, respectively, for hysteroscopy without biopsy; and both were 100% for biopsy. Statistical significance was considered at p < 0.05 and confidence intervals were calculated at 95%. CONCLUSIONS: In postmenopausal women with metrorrhagia, the first action to take is to do a transvaginal ultrasound, followed by en endometrial study, but only if the endometrium is irregular or endometrial thickness is >= 5 mm; in asymptomatic women, the cut-off point should be set at 10 mm. The immediate method of choice is an ambulatory biopsy. PMID- 27279855 TI - Empirical use of antibiotic therapy in the prevention of early onset sepsis in neonates: a pilot study. AB - INTRODUCTION: To identify and assess the characteristics, risk and outcome of neonates treated with empiric antibiotics for suspected early onset sepsis (EOS). MATERIAL AND METHODS: This is a retrospective study conducted at a Malaysian government hospital. Records of neonatal patients admitted within 72 h of life and prescribed with empirical antibiotic therapy for suspected EOS were reviewed. RESULTS: Three hundred and twenty-three cases met the inclusion criteria and were divided into gestational age (premature < 36 weeks; term >= 37 weeks) and birth weight (low birth weight (LBW) < 2.5 kg; normal body weight (NBW) >= 2.5 kg) groups. Premature (n = 197) and LBW (n = 194) neonates required significantly longer hospital stay, a higher degree of ventilator support and more surfactant (p = 0.001). More than 90.0% of premature and LBW neonates were diagnosed with respiratory distress syndrome, congenital pneumonia and presumed sepsis. Term (n = 123) and NBW (n = 129) neonates had greater maternal risk factors, especially meconium-stained amniotic fluid (MSAF) and perinatal asphyxia. The incidence of demonstrated EOS was 3.1%. Crystalline penicillin plus gentamicin was the standard therapy for all groups and was started within 24 h of life, with a mean treatment duration of ~4 days. The treatment success rate was 89.0%, and only LBW neonates showed a higher risk of overall treatment failure (OR = 3.75; 95% CI: 1.22-11.53). Seventy-four percent of term and NBW neonates discharged well, while 42.0% of premature and LBW neonates required referral. CONCLUSIONS: Crystalline penicillin plus gentamicin prescribed within 24 h of life is effective in the prevention of EOS. However, low birth weight neonates have a higher risk of treatment failure. PMID- 27279856 TI - The effectiveness of rotavirus vaccine in preventing acute gastroenteritis during rotavirus seasons among Polish children. AB - INTRODUCTION: Rotavirus is the main etiological cause of intestinal infections in children. Voluntary rotavirus vaccines were included in the Polish vaccination schedule in 2007. The aim of this study was to assess the effectiveness of a completed rotavirus vaccination course in preventing acute gastroenteritis in Polish infants during their first five years of life. MATERIAL AND METHODS: This was a retrospective cohort study conducted in Lesser Poland (Malopolska Province). The sample population included a group of 303 children who received the completed rotavirus vaccination course and 303 children not vaccinated against rotavirus. The date of the child's acute gastroenteritis diagnosis and his or her vaccination history were extracted from the physicians' records. Each kind of diagnosed acute gastroenteritis during winter-spring rotavirus seasons was treated as the endpoint. The relative risk of having gastrointestinal infection was assessed using the hazard ratio from the Cox proportional hazards regression model. RESULTS: In the examined group, 96 (15.8%) children had winter spring gastrointestinal infections. In the non-vaccinated children, the cumulative incidence of these infections in the first 5 years of life was 20.8%, whereas in the children vaccinated with Rotarix it was only 10.9%. Those who were vaccinated with Rotarix had a 44% reduction in the risk of a winter-spring acute gastroenteritis infection compared to those not vaccinated with Rotarix (p = 0.005). Birth weight less than 2500 g increased the risk of the infection twofold and also reached statistical significance (p = 0.044). CONCLUSIONS: The results showed that Rotarix is effective in preventing acute gastroenteritis in Polish children during rotavirus seasons. PMID- 27279857 TI - Color Doppler dynamic tissue perfusion measurement: a novel tool in the assessment of renal parenchymal perfusion in children with vesicoureteral reflux. AB - INTRODUCTION: Vesicoureteral reflux (VUR) occurs in 20-50% of children suffering from recurrent urinary tract infections (UTIs) and is associated with an increased risk of renal scarring and impaired renal function. Early detection of renal perfusion deterioration would allow for the implementation of more aggressive treatment and potentially prevent further damage to the renal parenchyma. The aim of the study was to assess renal parenchymal perfusions in children with recurrent UTIs with and without coexisting VUR, and compare the findings with the results of healthy patients. MATERIAL AND METHODS: Color Doppler sonographic dynamic renal parenchymal perfusion measurements were performed with PixelFlux (Chameleon-Software, Germany) software in 77 children with recurrent UTIs and coexisting VUR and in 30 children with UTIs without VUR. The findings were compared with the results of 53 healthy children. RESULTS: Cortical parenchymal perfusion of children suffering from UTIs and VUR was significantly reduced when compared to the control group. Statistically significant differences (p < 0.05) were found in all perfusion parameters (i.e. mean velocity (v mix ), mean perfused area (A mix ), mean perfusion intensity (I mix ), tissue pulsatility index (TPI), and tissue resistance index (TRI)) between the control group and children suffering from UTIs and VUR, particularly VUR grades III and IV. There were no significant differences between the UTI group and the control group. No differences were found between the controls and VUR grade II. CONCLUSIONS: Renal parenchymal perfusion decreases significantly with higher grades of VUR. PMID- 27279858 TI - Active hospital-based surveillance of invasive pneumococcal disease and clinical pneumonia in infants and young children in two Polish counties. AB - INTRODUCTION: Invasive pneumococcal disease (IPD) incidence, serotype distribution, and antibiotic susceptibility of Streptococcus pneumoniae were estimated in children aged 28 days to < 60 months. MATERIAL AND METHODS: One-year prospective, hospital-based surveillance was conducted starting on February 15, 2008, at two children's hospitals serving the city and surrounding county of Poznan and Poznanski, Poland. Eligible children had fever >= 39.0 degrees C or physician-suspected IPD. Blood cultures were obtained from all children, cerebrospinal fluid in suspected meningitis cases, and chest radiographs (CXRs) in suspected pneumonia cases. RESULTS: Seven of 1,581 eligible children had confirmed IPD. Estimated IPD incidence per 100,000 children was 11.89 (95% CI: 4.78-24.50) overall and 20.1 (95% CI: 6.52-46.84) in subjects aged 28 days to < 24 months. One S. pneumoniae isolate of each of the following serotypes was obtained: 6B, 14, 23A, 23F, and 33F. Two isolates were resistant to both trimethoprim-sulfamethoxazole and erythromycin. Clinical pneumonia incidence among children aged 28 days to < 24 months and 24 months to < 60 months was 3,151.3 (95% CI: 2934.7-3379.7) and 962.7 (95% CI: 861.2-10,072.9) per 100,000 children, respectively. CXR-confirmed pneumonia rates in the same groups were 1,035.7 (95% CI: 913.2-1,170.1) and 379.8 (95% CI: 317.1-451.3) per 100,000 children, respectively. CONCLUSIONS: IPD is an important cause of morbidity in Poznan and Poznanski county, Poland. Among participants aged < 5 years with fever or suspected IPD, pneumonia was the most common diagnosis and was highest in children aged < 24 months. PMID- 27279859 TI - Colonization of multidrug resistant pathogens in a hybrid pediatric cardiac surgery center. AB - INTRODUCTION: The incidence of multidrug resistant microorganisms worldwide is increasing. The aim of the study was to present institutional experience with the multidrug resistant microorganism colonization patterns observed in children with congenital heart diseases hospitalized in a hybrid pediatric cardiac surgery center. MATERIAL AND METHODS: Microbiological samples were routinely collected in all children admitted to our department. All microbiological samples were analyzed with regard to multidrug resistant microorganisms: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Gram negative rods producing extended-spectrum beta-lactamases (ESBL), multidrug resistant Gram-negative rods (MDR-GNRs), carbapenemase-producing Klebsiella pneumoniae (KPC), carbapenem-resistant Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA). RESULTS: In 30 (9%) swabs 'alert' pathogens from the above group of listed microorganisms were found. All positive swabs were isolated in 19 (16.1%) children. Multidrug resistant pathogen colonization was statistically significantly more often observed in children admitted from other medical facilities than in children admitted from home (38% vs. 10%, p = 0.0089). In the group of children younger than 6 months 'alert' pathogen were more often observed than in older children (34.1% vs. 5.4%, p < 0.001). CONCLUSIONS: Preoperative multidrug resistant pathogen screening in children admitted and referred for congenital heart disease procedures may be of great importance since many of these patients are colonized with resistant bacteria. Knowledge of the patient's microbiome is important in local epidemiological control along with tailoring the most effective preoperative prophylactic antibiotic for each patient. The impact of preoperative screening on postoperative infections and other complications requires further analysis. PMID- 27279861 TI - Medulloblastoma: molecular pathways and histopathological classification. AB - Malignant brain tumors are the leading cause of cancer death among pediatric patients, and medulloblastoma constitutes 20% of them. Currently, the treatment is risk-adapted. Maximum surgical resection is recommended, always followed by chemotherapy and neuroaxis radiotherapy. In spite of the improving survival rate, survivors succumb to treatment-induced side effects. To reduce toxic effects, molecular-targeted treatment is proposed. Medulloblastoma research is very robust, and new articles on the subject are published daily. In the current review we have tried to bring together molecular pathophysiology of the neoplasm and current pathological classification, thus making an effort to relate tumor biology and the histological picture. PMID- 27279860 TI - Molecular mechanisms of statin intolerance. AB - Statins reduce cardiovascular morbidity and mortality in primary and secondary prevention. Despite their efficacy, many persons are unable to tolerate statins due to adverse events such as hepatotoxicity and myalgia/myopathy. In the case of most patients, it seems that mild-to-moderate abnormalities in liver and muscle enzymes are not serious adverse effects and do not outweigh the benefits of coronary heart disease risk reduction. The risk for mortality or permanent organ damage ascribed to statin use is very small and limited to cases of myopathy and rhabdomyolysis. Statin-induced muscle-related adverse events comprise a highly heterogeneous clinical disorder with numerous, complex etiologies and a variety of genetic backgrounds. Every patient who presents with statin-related side effects cannot undergo the type of exhaustive molecular characterization that would include all of these mechanisms. Frequently the only solution is to either discontinue statin therapy/reduce the dose or attempt intermittent dosing strategies at a low dose. PMID- 27279863 TI - Successful combination treatment of a bifocal secretory germinoma with brain stem compression in a 17-year-old girl. PMID- 27279862 TI - Undescended testis - current trends and guidelines: a review of the literature. AB - The best mode of undescended testis (UDT) treatment remains controversial. However, knowledge gained from randomized controlled studies and meta-analyses allowed different groups of researchers to set out guidelines on management of patients with UDT. The authors reviewed recent literature and came to the following conclusions: (1) Hormonal treatment is not recommended, considering both the immediate results (only 15-20% of retained testes descend) and the possible long-term adverse effects on spermatogenesis. (2) Surgery is the treatment of choice; orchiopexy is successful in about 95% of UDT, with a low rate of complications (about 1%). (3) Orchiopexy should be performed between 12 and 18 months of age, or at first contact if diagnosed later. PMID- 27279864 TI - Primary adrenal schwannoma with catecholamine hypersecretion. PMID- 27279865 TI - Erythema multiforme syndrome associated with acute acquired cytomegalovirus infection. PMID- 27279866 TI - Diagnostic one-stop-shop in suspected coronary artery disease gets closer. Coronary computed tomography angiography based fractional flow reserve. PMID- 27279867 TI - Which parameters are important before attempting chronic total occlusions recanalization? PMID- 27279868 TI - Fetal cardiac interventions: clinical and experimental research. AB - Fetal cardiac interventions for congenital heart diseases may alleviate heart dysfunction, prevent them evolving into hypoplastic left heart syndrome, achieve biventricular outcome and improve fetal survival. Candidates for clinical fetal cardiac interventions are now restricted to cases of critical aortic valve stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic left heart syndrome with an intact or highly restrictive atrial septum as well as fetal heart block. The therapeutic options are advocated as prenatal aortic valvuloplasty, pulmonary valvuloplasty, creation of interatrial communication and fetal cardiac pacing. Experimental research on fetal cardiac intervention involves technical modifications of catheter-based cardiac clinical interventions and open fetal cardiac bypass that cannot be applied in human fetuses for the time being. Clinical fetal cardiac interventions are plausible for midgestation fetuses with the above-mentioned congenital heart defects. The technical success, biventricular outcome and fetal survival are continuously being improved in the conditions of the sophisticated multidisciplinary team, equipment, techniques and postnatal care. Experimental research is laying the foundations and may open new fields for catheter-based clinical techniques. In the present article, the clinical therapeutic options and experimental fetal cardiac interventions are described. PMID- 27279869 TI - Twelve months clinical outcome after bioresorbable vascular scaffold implantation in patients with stable angina and acute coronary syndrome. Data from the Polish National Registry. AB - INTRODUCTION: There are limited data describing bioresorbable vascular scaffold (BVS) implantation in complex lesions. Only short-term clinical outcomes are available for patients with acute coronary syndrome (ACS). AIM: To evaluate 12 month clinical outcome, safety and effectiveness of BVS implantation in complex lesions and in stable angina (SA) or ACS. MATERIAL AND METHODS: Five hundred ninety-one patients with SA/ACS were enrolled between October 2012 and November 2013 in 30 invasive cardiology centres in Poland. At least one BVS implantation during percutaneous coronary intervention (PCI) was the only inclusion criteria. The clinical endpoint was the occurrence of a major adverse cardiovascular event (MACE) (all-cause death, myocardial infarction (MI), clinically driven target lesion revascularisation (TLR) with urgent PCI or target vessel revascularisation (TVR) with urgent coronary artery bypass grafting (CABG)) and device-oriented composite endpoint (DOCE) (cardiac death, urgent target vessel revascularisation with PCI/CABG, target vessel MI) during 12-month follow-up. RESULTS: After 12 months TLR with urgent PCI was significantly more often reported in patients with diagnosed UA (4.59%; p < 0.02) in comparison with other PCI indications. No significant differences were found in terms of composite MACE endpoint, cumulative MACE (p = 0.09), stent thrombosis (p = 0.2) or restenosis (p = 0.2). There were no significant differences in cumulative MACE and composite MACE endpoint between patients with no/mild versus moderate/severe tortuosity and no/mild versus moderate/severe calcification of the target vessel. No significant difference was found between groups of patients with or without bifurcation of the target vessel. Device-oriented composite endpoint was significantly more often reported in the ACS group (3.2% vs. 0.47%; p < 0.03), most frequently in patients with diagnosed UA (5.5%). CONCLUSIONS: Bioresorbable vascular scaffold can be successfully and safely used for ACS treatment and in lesions of higher complexity. PMID- 27279870 TI - Stent sizing strategies in renal artery stenting: the comparison of conventional invasive renal angiography with renal computed tomographic angiography. AB - INTRODUCTION: Randomized trials comparing invasive treatment of renal artery stenosis with standard pharmacotherapy did not show substantial benefit from revascularization. One of the potential reasons for that may be suboptimal procedure technique. AIM: To compare renal stent sizing using two modalities: three-dimensional renal computed tomography angiography (CTA) versus conventional angiography. MATERIAL AND METHODS: Forty patients (41 renal arteries), aged 65.1 +/-8.5 years, who underwent renal artery stenting with preprocedural CTA performed within 6 months, were retrospectively analyzed. In CTA analysis, reference diameter (CTA-D) and lesion length (CTA_LL) were measured and proposed stent diameter and length were recorded. Similarly, angiographic reference diameter (ANGIO_D) and lesion length (ANGIO_LL) as well as proposed stent dimensions were obtained by visual estimation. RESULTS: The median CTA_D was 0.5 mm larger than the median ANGIO_D (p < 0.001). Also, the proposed stent diameter in CTA evaluation was 0.5 mm larger than that in angiography (p < 0.0001). The median CTA_LL was 1 mm longer than the ANGIO_LL (p = NS), with significant correlation of these variables (r = 0.66, p < 0.0001). The median proposed stent length with CTA was equal to that proposed with angiography. The median diameter of the implanted stent was 0.5 mm smaller than that proposed in CTA (p < 0.0005) and identical to that proposed in angiography. The median length of the actual stent was longer than that proposed in angiography (p = 0.0001). CONCLUSIONS: Renal CTA has potential advantages as a tool adjunctive to angiography in appropriate stent sizing. Careful evaluation of the available CTA scans may be beneficial and should be considered prior to the planned procedure. PMID- 27279871 TI - Early- and mid-term outcomes after transcatheter aortic valve implantation. Data from a single-center registry. AB - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a less invasive treatment option for elderly, high-risk patients with symptomatic severe aortic stenosis (AS) than aortic valve replacement. More importantly, TAVI improves survival and quality of life as compared to medical treatment in inoperable patients. AIM: To assess early- and mid-term clinical outcomes after TAVI. MATERIAL AND METHODS: All consecutive high-risk patients with severe symptomatic AS undergoing TAVI from November 2008 to August 2014 were enrolled. The clinical and procedural characteristics, as well as clinical outcomes including mortality during 12-month follow-up, were assessed. RESULTS: A total of 101 consecutive patients underwent TAVI for native aortic valve stenosis (100%). Patients were elderly, with a median age of 81.0 (76.0-84.0) years, 60.4% were female and 83.2% presented with NYHA III/IV. Median baseline EuroSCORE I and STS scores were 14.0 (10.0-22.5)% and 12.0 (5.0-24.0)%, respectively. The main periprocedural and in hospital complications were minor vascular complications, bleeding requiring blood transfusions, and the need for a permanent pacemaker. In-hospital, 30-day, 6-month and 12-month mortality rates were 6.9%, 10.9%, 15.8% and 17.8%, respectively. CONCLUSIONS: A mortality rate of < 20% after 12 months seems acceptable given the high-risk population enrolled. PMID- 27279872 TI - Transcatheter closure of paravalvular leaks using a paravalvular leak device - a prospective Polish registry. AB - INTRODUCTION: Transcatheter paravalvular leak closure (TPVLC) has become an established treatment option but is mostly performed with off-label use of different non-dedicated occluders. The first one specifically designed for TPVLC is the paravalvular leak device (PLD - Occlutech). AIM: We present initial short term results of a prospective registry intended to assess the safety and efficacy of TPVLC with PLD. MATERIAL AND METHODS: We screened patients with paravalvular leak (PVL) after surgical valve replacement (SVR). Heart failure symptoms and/or hemolytic anemia were indications for TPVLC. Patients were selected according to PVL anatomy by RT 3D TEE. Only those considered appropriate for closure with a single PLD were enrolled. The procedures were performed via transvascular or transapical access using type W (waist) PLDs only. RESULTS: Thirty patients with 34 PVLs (18 aortic, 16 mitral) were included. We implanted 35 PLDs with a total device success rate of 94.3% (100% for aortic, 88.2% for mitral). The procedural success rate, encompassing device success without in-hospital complications, was 94.1% (100% for aortic, 93.8% for mitral). During the follow-up period we recorded an increase of hemoglobin concentration (3.9 to 4.1 g/dl), red blood count (11.6 to 12.2 M/mm(3)) and functional improvement by NYHA class. CONCLUSIONS: Paravalvular leak device type W is a promising TPVLC device, but meticulous preselection of patients based on imaging of PVL anatomy is a prerequisite. A PLD should only be chosen for channels shorter than 5 mm. Size of the device should match the PVL cross-sectional area without any oversizing. Such an approach facilitates high device and procedural success rates. PMID- 27279873 TI - Pulmonary artery rupture as a complication of Swan-Ganz catheter application. Diagnosis and endovascular treatment: a single centre's experience. AB - INTRODUCTION: The placement of a Swan-Ganz catheter into the pulmonary artery may lead to a number of complications (2-17%). In less than 0.2% of cases Swan-Ganz catheterization results in serious vascular damage - pulmonary artery rupture (PAR). This paper presents two distinct forms of iatrogenic PAR treated endovascularly using different vascular devices. AIM: To evaluate the effectiveness of endovascular treatment and the application of different types of vascular devices in the management of pulmonary artery rupture caused by Swan Ganz catheterization. MATERIAL AND METHODS: In this retrospective study we evaluated 2 patients in whom Swan-Ganz catheter application was used for perioperative monitoring and resulted in pulmonary artery rupture. This complication was treated endovascularly by means of interventional cardiology. RESULTS: We report the cases of 2 patients with a pulmonary artery pseudoaneurysm formed in the perioperative period. In case 1, a single, 4-loop, 3 mm diameter coil was implanted. In case 2, a 5 mm Amplatzer Vascular Plug IV was applied. In both cases, the endovascular approach resulted in total occlusion of the feeding artery and reduced further extravasation of the blood. CONCLUSIONS: Despite its extremely low incidence, iatrogenic PAR is a serious, life-threatening complication of Swan-Ganz catheterization that requires urgent attention. Among available methods of treatment, percutaneous embolization is a relatively quick, safe, accurate and highly effective alternative to traumatizing surgery. PMID- 27279874 TI - Percutaneous retrieval of centrally embolized fragments of central venous access devices or knotted Swan-Ganz catheters. Clinical report of 14 retrievals with detailed angiographic analysis and review of procedural aspects. AB - INTRODUCTION: Totally implantable venous access systems (TIVAS), Swan-Ganz (SG) and central venous catheters (CVC) allow easy and repetitive entry to the central cardiovascular system. Fragments of them may be released inadvertently into the cardiovascular system during their insertion or as a result of mechanical complications encountered during long-term utilization. AIM: To present results of percutaneous retrieval of embolized fragments of central venous devices or knotted SG and review the procedural aspects with a series of detailed angiographies. MATERIAL AND METHODS: Between January 2003 and December 2012 there were 14 (~0.025%) successful retrievals in 13 patients (44 +/-16 years, 15% females) of embolized fragments of TIVAS (n = 10) or CVC (n = 1) or of dislodged guide-wires (n = 2) or knotted SG (n = 1). RESULTS: Foreign bodies with the forward end located in the right ventricle (RV), as well as those found in the pulmonary artery (PA), often required repositioning with a pigtail catheter as compared to those catheter fragments which were located in the right atrium (RA) and/or great vein and possessed an accessible free end allowing their direct ensnarement with the loop snare (57.0% (4/7) vs. 66.7% (2/3) vs. 0.0% (0/3); p = 0.074 respectively). Procedure duration was 2-3 times longer among catheters retrieved from the PA than among those with the forward edge located in the RV or RA (30 (18-68) vs. 13.5 (11-37) vs. 8 min (8-13); p = 0.054 respectively). The SG catheter knotted in the vena cava superior (VCS) was encircled with the loop snare introduced transfemorally, subsequently cut at its skin entrance and then pulled down inside the 14 Fr vascular sheath. CONCLUSIONS: By using the pigtail catheter and the loop snare, it is feasible to retrieve centrally embolized fragments or knotted central venous access devices. PMID- 27279876 TI - A case of percutaneous modified Blalock-Taussig shunt downsize with multiple stent-in-graft technique. PMID- 27279875 TI - Do preoperative C-reactive protein and mean platelet volume levels predict development of postoperative atrial fibrillation in patients undergoing isolated coronary artery bypass grafting? AB - INTRODUCTION: Atrial fibrillation (AF) after coronary artery bypass grafting (CABG) operation is associated with increased risk of prolonged hospitalisation, health expenses and adverse clinical outcomes. AIM: To investigate the relationship of atrial fibrillation after an isolated coronary artery bypass operation with levels of mean platelet volume and C-reactive protein. MATERIAL AND METHODS: Among 1240 patients who underwent operations for isolated coronary artery bypass grafting with cardiopulmonary bypass between January 2007 and May 2014, 1138 (91.8%) patients with preoperative normal sinusal rhythm were enrolled in the study. Patients were assigned to group 1 (n = 294) comprising patients who developed atrial fibrillation in the first 72 postoperative hours or group 2 (n = 844) comprising patients who remained in normal sinusal rhythm in the postoperative period. RESULTS: The incidence of postoperative atrial fibrillation was 25.8%. The preoperative mean platelet volume (fl) and C-reactive protein (mg/dl) values in group 1 were 9.1 +/-0.5 and 1.1 +/-0.9 respectively, while these values were 8.3 +/-0.6 and 0.5 +/-0.3 respectively in group 2, which was statistically significant (p = 0.0001). Length of stay in the hospital (p = 0.0001) was higher in group 1. The values of mean platelet volume (fl) and mean C reactive protein (mg/dl) were 9.9 +/-0.9 and 30.9 +/-3.4 respectively in group 1, while the values of mean platelet volume (fl) and mean C-reactive protein (mg/dl) were 8.8 +/-0.6 and 24.9 +/-4.8 respectively in group 2 (p = 0.0001 for mean platelet volume, p = 0.0001 for C-reactive protein). The difference between the groups was statistically significant in terms of postoperative neurologic events (p = 0.0001) and hospital mortality (p = 0.001). Increased C-reactive protein and mean platelet volume levels were found to be independent predictors of postoperative atrial fibrillation. CONCLUSIONS: In our study, elevated preoperative mean platelet volume and C-reactive protein levels were associated with development of postoperative atrial fibrillation. PMID- 27279877 TI - The successful retrieval of a broken guide wire from the diagonal branch of the left anterior descending coronary artery complicated by partial stent rolling. PMID- 27279878 TI - New endovascular techniques for treatment of life-threatening Takayasu arteritis. PMID- 27279879 TI - Successful percutaneous coronary intervention after transcatheter aortic valve implantation with CoreValve bioprosthesis. PMID- 27279880 TI - Retrograde transcatheter closure of ventricular septal defect with Amplatzer Duct Occluder II. PMID- 27279881 TI - Diffuse coronary artery aneurysms involving three major vessels in a patient with Behcet's disease. PMID- 27279882 TI - Very, very late stent thrombosis triggered by in-stent neoatherosclerosis: optical coherence tomography findings. PMID- 27279883 TI - Percutaneous right atrial pacemaker lead repositioning using a regular deflectable ablation catheter. PMID- 27279885 TI - Clinical features and prognostic factors in drowning children: a regional experience. AB - PURPOSE: This study aimed to evaluate the clinical features of children who have survived a water submersion incident, and to identify risk factors for prognosis. METHODS: We retrospectively reviewed the medical records of patients who experienced submersion between January 2005 and December 2014. The patients were classified into 2 groups, according to complications, and prognostic factors were evaluated. RESULTS: During the study period, 29 children experienced submersion (20 boys and 9 girls; mean age, 83.8+/-46.4 months). Submersion occurred most commonly in the summer, with the peak incidence in August. The most frequent Szpilman clinical score was grade 5 (13 patients; 44.8%), followed by grade 6 (7 patients; 24.1%), and grades 1 or 2 (3 patients; 10.3%). Five children (17.2%) in the poor prognosis group died or had hypoxic ischemic encephalopathy, and the overall mortality rate was 6.9%. Poor prognosis after submersion was associated with lower consciousness levels (P=0.003), higher Szpilman scores (P=0.007), greater need for intubation and mechanical ventilator support (P=0.001), and longer duration of oxygen therapy (P=0.015). Poor prognosis was also associated with lower bicarbonate levels (P=0.038), as well as higher sodium, aspartate transaminase (AST), and alanine transaminase (ALT) levels (P=0.034, P=0.006, and P=0.005, respectively). Szpilman clinical scores were positively correlated with consciousness levels (r=0.489, P=0.002) and serum liver enzyme levels (AST and ALT; r=0.521, P=0.004). CONCLUSION: We characterized the prognostic factors associated with submersion outcomes, using the Szpilman clinical score, which is comparable to consciousness level for predicting mortality. PMID- 27279884 TI - Pathogenesis of minimal change nephrotic syndrome: an immunological concept. AB - Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children. PMID- 27279886 TI - The relationships among birth season, sunlight exposure during infancy, and allergic disease. AB - PURPOSE: The recent increase in the prevalence of allergic diseases is hypothetically attributed to immune dysregulation in turn caused by a reduction in exposure to sunlight. We explored relationships between birth season, sunlight exposure, exercise duration, and an allergic disease. METHODS: We performed a questionnaire-based survey on allergic diseases among elementary school students. Birth time was categorized according to the season (summer and winter). RESULTS: The prevalence of atopic dermatitis (AD) "symptoms ever" was higher in the children born in winter than in those born in summer (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.03-1.49; P=0.024). Birth in winter was associated with an increase in the "symptoms in the past 12 months" prevalence of food allergy (FA) (aOR, 1.56; 95% CI, 1.09-2.24; P=0.015). The lifetime prevalence of allergic diseases except FA was higher in the children whose parents considered their sunlight exposure prior to 24 months of ageas inadequate than those who considered their exposure as adequate ("diagnosis ever" asthma: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; allergic rhinitis [AR]: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; AD: aOR, 1.26; 95% CI, 1.06-1.51; P=0.01). Neither recent sunlight exposure nor exercise duration was associated with the prevalence of an allergic disease. CONCLUSION: Birth in winter may be associated with development of AD and FA. Inadequate sunlight exposure before the age of 24 months might possibly increase the risks of development of asthma, AR, and AD. PMID- 27279887 TI - Efficacy of proton pump inhibitors and H2 blocker in the treatment of symptomatic gastroesophageal reflux disease in infants. AB - PURPOSE: Gastroesophageal reflux disease (GERD) occurs in pediatric patients when reflux of gastric contents presents with troublesome symptoms. The present study compared the effects of omeprazole and ranitidine for the treatment of symptomatic GERD in infants of 2-12 months. METHODS: This study was a clinical randomized double-blind trial and parallel-group comparison of omeprazole and ranitidine performed at Children Training Hospital in Tabriz, Iran. Patients received a standard treatment for 2 weeks. After 2 weeks, the patients with persistent symptoms were enrolled in this randomized study. RESULTS: We enrolled 76 patients in the present study and excluded 16 patients. Thirty patients each were included in group A (ranitidine) and in group B (omeprazole). GERD symptom score for groups A and B was 47.17+/-5.62 and 51.93+/-5.42, respectively, with a P value of 0.54, before the treatment and 2.47+/-0.58 and 2.43+/-1.15, respectively, after the treatment (P=0.98). No statistically significant differences were found between ranitidine and omeprazole in their efficacy for the treatment of GERD. CONCLUSION: The safety and efficacy of ranitidine and omeprazole have been demonstrated in infants. Both groups of infants showed a statistically significant decrease in the score of clinical variables after the treatment. PMID- 27279888 TI - Lipopolysaccharide-binding protein plasma levels as a biomarker of obesity related insulin resistance in adolescents. AB - PURPOSE: Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. METHODS: The study included 87 adolescents aged 12-13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean age of the participants was 12.9+/-0.3 years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (7.8+/-1.9 ug/mL vs. 6.0+/-1.6 ug/mL, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. CONCLUSION: LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents. PMID- 27279889 TI - A giant choledochal cyst in infancy: a case report. AB - Choledochal cyst is a dilation that encloses the intrahepatic or both extra- and intrahepatic portions of the biliary ducts. Postnatally, ultrasonography is the initial diagnostic modality of choice, allowing for precise measurements of intra or extrahepatic duct dilatation and identification of stones and sludge. Symptoms depend on the age at presentation. Common bile duct malformations should be considered as a differential diagnosis of a cystic mass regardless of the cyst's size or patient's age, especially in children presenting with abdominal pain, jaundice, and palpable mass. To the best of our knowledge, we report the largest choledochal cyst in infancy. PMID- 27279890 TI - Bilateral iliac and popliteal arterial thrombosis in a child with focal segmental glomerulosclerosis. AB - Thromboembolic complications (TECs) are clinically important sequelae of nephrotic syndrome (NS). The incidence of TECs in children is approximately 2% 5%. The veins are the most commonly affected sites, particularly the deep veins in the legs, the inferior vena cava, the superior vena cava, and the renal veins. Arterial thrombosis, which is less common, typically occurs in the cerebral, pulmonary, and femoral arteries, and is associated with the use of steroids and diuretics. Popliteal artery thrombosis in children has been described in cases of traumatic dissection, osteochondroma, Mycoplasma pneumoniae infection, and fibromuscular dysplasia. We report of a 33-month-old girl with bilateral iliac and popliteal arterial thrombosis associated with steroid-resistant NS due to focal segmental glomerulosclerosis. Her treatment involved thrombectomy and intravenous heparinization, followed by oral warfarin for 8 months. Herein, we report a rare case of spontaneous iliac and popliteal arterial thrombosis in a young child with NS. PMID- 27279891 TI - A distributional approach to obtain adjusted comparisons of proportions of a population at risk. AB - BACKGROUND: Dichotomisation of continuous data has statistical drawbacks such as loss of power but may be useful in epidemiological research to define high risk individuals. METHODS: We extend a methodology for the presentation of comparison of proportions derived from a comparison of means for a continuous outcome to reflect the relationship between a continuous outcome and covariates in a linear (mixed) model without losing statistical power. The so called "distributional method" is described and using perinatal data for illustration, results from the distributional method are compared to those of logistic regression and to quantile regression for three different outcomes. RESULTS: Estimates obtained using the distributional method for the comparison of proportions are consistently more precise than those obtained using logistic regression. For one of the three outcomes the estimates obtained from the distributional method and from logistic regression disagreed highlighting that the relationships between outcome and covariate differ conceptually between the two models. CONCLUSION: When an outcome follows the required condition of distribution shift between exposure groups, the results of a linear regression model can be followed by the corresponding comparison of proportions at risk. This dual approach provides more precise estimates than logistic regression thus avoiding the drawback of the usual dichotomisation of continuous outcomes. PMID- 27279893 TI - Increased arterial stiffness parameters in panic disorder patients in long term treatment period. AB - BACKGROUND: The relationship between mental stress and cardiovascular disease has been shown in several studies. Panic disorder (PD) is also associated with cardiovascular disease due to increased risk of myocardial infarction. The aim of this study is to evaluate the association between arterial stiffness parameters and depression/anxiety scores in patients with PD. METHODS: The study population consisted of 25 patients with PD and 25 age-sex-matched healthy controls. Depression and anxiety levels were evaluated by Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. Determination of arterial stiffness parameters was conducted using a Mobil-O-Graph arteriograph system that detected signals from the brachial artery. RESULTS: While baseline characteristics were similar between two groups, BDI and BAI scores were significantly higher in patients with PD (p < 0.005). The pulse wave velocity (PWV) and Augmentation Index (AIx) were also significantly higher in patients with PD (p = 0.001, p = 0.006). There was a moderate correlation between PWV and AIx with BAI scores (r = 0.442, p = 0.001, r = 0.441, p = 0.001). AIx was also positively correlated with BDI scores (r = 0.415, p = 0.03). CONCLUSION: We demonstrated a significant relationship between arterial stiffness parameters and anxiety/depression scores in patients with PD who receive antidepressant treatment. PMID- 27279892 TI - Sea shell diversity and rapidly evolving secretomes: insights into the evolution of biomineralization. AB - An external skeleton is an essential part of the body plan of many animals and is thought to be one of the key factors that enabled the great expansion in animal diversity and disparity during the Cambrian explosion. Molluscs are considered ideal to study the evolution of biomineralization because of their diversity of highly complex, robust and patterned shells. The molluscan shell forms externally at the interface of animal and environment, and involves controlled deposition of calcium carbonate within a framework of macromolecules that are secreted from the dorsal mantle epithelium. Despite its deep conservation within Mollusca, the mantle is capable of producing an incredible diversity of shell patterns, and macro- and micro-architectures. Here we review recent developments within the field of molluscan biomineralization, focusing on the genes expressed in the mantle that encode secreted proteins. The so-called mantle secretome appears to regulate shell deposition and patterning and in some cases becomes part of the shell matrix. Recent transcriptomic and proteomic studies have revealed marked differences in the mantle secretomes of even closely-related molluscs; these typically exceed expected differences based on characteristics of the external shell. All mantle secretomes surveyed to date include novel genes encoding lineage-restricted proteins and unique combinations of co-opted ancient genes. A surprisingly large proportion of both ancient and novel secreted proteins containing simple repetitive motifs or domains that are often modular in construction. These repetitive low complexity domains (RLCDs) appear to further promote the evolvability of the mantle secretome, resulting in domain shuffling, expansion and loss. RLCD families further evolve via slippage and other mechanisms associated with repetitive sequences. As analogous types of secreted proteins are expressed in biomineralizing tissues in other animals, insights into the evolution of the genes underlying molluscan shell formation may be applied more broadly to understanding the evolution of metazoan biomineralization. PMID- 27279894 TI - Using IFN-gamma release assay to confirm tuberculin skin test improves the screening of latent tuberculosis infection in Italian healthcare workers. AB - BACKGROUND: Healthcare workers (HCWs) represent a tuberculosis (TB) risk group for a wide range of tasks in healthcare, even in countries with low TB incidence, like Italy. Latent Tuberculosis Infection (LTBI) screening programs are an important tool for TB prevention in these setting. METHODS: A retrospective study under a LTBI screening program among HCWs at the Siena University Hospital (Italy), was conducted between September 2011 and July 2015. Tuberculin Skin Test (TST) was used as a first level examination; all TST-positive cases were tested with QuantiFERON-TB Gold In-Tube (QFT-GIT) test, together with a group of TST negative subjects. RESULTS: Among the 2136 HCWs screened, 144 (6.7 %) were TST positive and therefore tested with QFT-GIT, confirming a positive result in 36 cases (25 %). Agreement between two tests was poor (k = 0.092; 95 %, Confidence Interval [CI]- 0.048-0.136, p = 0.002). Among TST-positive cases, discordant results occurred more frequently in BCG vaccinated than unvaccinated HCWs (86.3 %, p < 0.001). The probability of a QFT-GIT-positive result increased according to the TST diameter (p = 0.001). No putative risk factor was associated with LTBI occurrence. CONCLUSIONS: The use of QFT-GIT test as a second step in TST-positive cases offers an appropriate tool for LTBI detection, especially among BCG vaccinated HCWs. PMID- 27279895 TI - RhizoTubes as a new tool for high throughput imaging of plant root development and architecture: test, comparison with pot grown plants and validation. AB - BACKGROUND: In order to maintain high yields while saving water and preserving non-renewable resources and thus limiting the use of chemical fertilizer, it is crucial to select plants with more efficient root systems. This could be achieved through an optimization of both root architecture and root uptake ability and/or through the improvement of positive plant interactions with microorganisms in the rhizosphere. The development of devices suitable for high-throughput phenotyping of root structures remains a major bottleneck. RESULTS: Rhizotrons suitable for plant growth in controlled conditions and non-invasive image acquisition of plant shoot and root systems (RhizoTubes) are described. These RhizoTubes allow growing one to six plants simultaneously, having a maximum height of 1.1 m, up to 8 weeks, depending on plant species. Both shoot and root compartment can be imaged automatically and non-destructively throughout the experiment thanks to an imaging cabin (RhizoCab). RhizoCab contains robots and imaging equipment for obtaining high-resolution pictures of plant roots. Using this versatile experimental setup, we illustrate how some morphometric root traits can be determined for various species including model (Medicago truncatula), crops (Pisum sativum, Brassica napus, Vitis vinifera, Triticum aestivum) and weed (Vulpia myuros) species grown under non-limiting conditions or submitted to various abiotic and biotic constraints. The measurement of the root phenotypic traits using this system was compared to that obtained using "classic" growth conditions in pots. CONCLUSIONS: This integrated system, to include 1200 Rhizotubes, will allow high-throughput phenotyping of plant shoots and roots under various abiotic and biotic environmental conditions. Our system allows an easy visualization or extraction of roots and measurement of root traits for high throughput or kinetic analyses. The utility of this system for studying root system architecture will greatly facilitate the identification of genetic and environmental determinants of key root traits involved in crop responses to stresses, including interactions with soil microorganisms. PMID- 27279897 TI - Systematic change in global patterns of streamflow following volcanic eruptions. AB - Following large explosive volcanic eruptions precipitation decreases over much of the globe1-6, particularly in climatologically wet regions4,5. Stratospheric volcanic aerosols reflect sunlight, which reduces evaporation, whilst surface cooling stabilises the atmosphere and reduces its water-holding capacity7. Circulation changes modulate this global precipitation reduction on regional scales1,8-10. Despite the importance of rivers to people, it has been unclear whether volcanism causes detectable changes in streamflow given large natural variability. Here we analyse observational records of streamflow volume for fifty large rivers from around the world which cover between two and 6 major volcanic eruptions in the 20th and late 19th century. We find statistically significant reductions in flow following eruptions for the Amazon, Congo, Nile, Orange, Ob, Yenisey and Kolyma amongst others. When data from neighbouring rivers are combined - based on the areas where climate models simulate either an increase or a decrease in precipitation following eruptions - a significant (p<0.1) decrease in streamflow following eruptions is detected in northern South American, central African and high-latitude Asian rivers, and on average across wet tropical and subtropical regions. We also detect a significant increase in southern South American and SW North American rivers. This suggests that future volcanic eruptions could substantially affect global water availability. PMID- 27279896 TI - Wells criteria for DVT is a reliable clinical tool to assess the risk of deep venous thrombosis in trauma patients. AB - BACKGROUND: Deep Vein Thrombosis (DVT) is a common complication in trauma patients. Venous duplex surveillance is used widely for the diagnosis of DVT, however, there is controversy concerning its appropriate use. The Wells criterion is a clinically validated scoring system in an outpatient setting, but its use in trauma patients has not been studied. This study evaluated the application of the Wells scoring system in trauma population. METHODS: Wells scores were calculated retrospectively for all patients who were admitted to the trauma service and underwent Venous Duplex Scanning (VDS) at the author's institution between 2012 and 2013. Correlation of Wells score with DVT and its efficacy in risk stratifying the patients after trauma was analyzed using linear correlation and receiver operating characteristic (ROC) curve. Sensitivity and specificity of Wells score in ruling out or ruling in DVT were calculated in various risk groups. RESULTS: Of 298 patients evaluated, 18 (6 %) patients were positive for DVT. A linear correlation was present between Wells score and DVT with R (2) = 0.88 (p = 0.0016). Median Wells score of patients without DVT was 1 (1-3) compared to a median score of 2 (1-5) in those with DVT (p < 0.0001). In low risk patients (scores <1), Wells scoring was able to rule out the possibility of DVT with a sensitivity of 100 % and NPV of 100 %, while in moderate-high risk patients (scores >=2), it was able to predict DVT with a specificity of 90 %. Area under ROC curve was 0.859 (p < 0.0001) demonstrating the accuracy of Wells scoring system for DVT risk stratification in post trauma patients. CONCLUSIONS: A Wells score of <1 can reliably rule out the possibility of DVT in the trauma patients. Risk of developing DVT correlates linearly with Wells score, establishing it as a valid pretest tool for risk stratification. PMID- 27279898 TI - Prospective associations between adolescent mental health problems and positive mental wellbeing in early old age. AB - BACKGROUND: Mental health problems in adolescence are predictive of future mental distress and psychopathology; however, few studies investigated adolescent mental health problems in relation to future mental wellbeing and none with follow-up to older age. AIMS: To test prospective associations between adolescent mental health problems and mental wellbeing and life satisfaction in early old age. METHODS: A total of 1561 men and women were drawn from the Medical Research Council National Survey of Health and Development (the British 1946 birth cohort). Teachers had previously completed rating scales to assess emotional adjustment and behaviours, which allowed us to extract factors of mental health problems measuring self-organisation, behavioural problems, and emotional problems during adolescence. Between the ages of 60-64 years, mental wellbeing was assessed using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and life satisfaction was self-reported using the Satisfaction with Life Scale (SWLS). RESULTS: After controlling for gender, social class of origin, childhood cognitive ability, and educational attainment, adolescent emotional problems were independently inversely associated with mental wellbeing and with life satisfaction. Symptoms of anxiety/depression at 60-64 years explained the association with life satisfaction but not with mental wellbeing. Associations between adolescent self-organisation and conduct problems and mental wellbeing and life satisfaction were of negligible magnitude, but higher childhood cognitive ability significantly predicted poor life satisfaction in early old age. CONCLUSIONS: Adolescent self-organisation and conduct problems may not be predictive of future mental wellbeing and life satisfaction. Adolescent emotional problems may be inversely associated with future wellbeing, and may be associated with lower levels of future life satisfaction through symptoms of anxiety/depression in early old age. Initiatives to prevent and treat emotional problems in adolescence may have long-term benefits which extend into older age. PMID- 27279899 TI - Anaerobic detoxification of acetic acid in a thermophilic ethanologen. AB - BACKGROUND: The liberation of acetate from hemicellulose negatively impacts fermentations of cellulosic biomass, limiting the concentrations of substrate that can be effectively processed. Solvent-producing bacteria have the capacity to convert acetate to the less toxic product acetone, but to the best of our knowledge, this trait has not been transferred to an organism that produces ethanol at high yield. RESULTS: We have engineered a five-step metabolic pathway to convert acetic acid to acetone in the thermophilic anaerobe Thermoanaerobacterium saccharolyticum. The first steps of the pathway, a reversible conversion of acetate to acetyl-CoA, are catalyzed by the native T. saccharolyticum enzymes acetate kinase and phosphotransacetylase. ack and pta normally divert 30% of catabolic carbon flux to acetic acid; however, their re introduction in evolved ethanologen strains resulted in virtually no acetic acid production. Conversion between acetic acid and acetyl-CoA remained active, as evidenced by rapid (13)C label transfer from exogenous acetate to ethanol. Genomic re-sequencing of six independently evolved ethanologen strains showed convergent mutations in the hfs hydrogenase gene cluster, which when transferred to wildtype T. saccharolyticum conferred a low acid production phenotype. Thus, the mutated hfs genes effectively separate acetic acid production and consumption from central metabolism, despite their intersecting at the common intermediate acetyl-CoA. To drive acetic acid conversion to a less inhibitory product, the enzymes thiolase, acetoacetate:acetate CoA-transferase, and acetoacetate decarboxylase were assembled in T. saccharolyticum with genes from thermophilic donor organisms that do not natively produce acetone. The resultant strain converted acetic acid to acetone and ethanol while maintaining a metabolic yield of 0.50 g ethanol per gram carbohydrate. CONCLUSIONS: Conversion of acetic acid to acetone results in improved ethanol productivity and titer and is an attractive low-cost solution to acetic acid inhibition. PMID- 27279900 TI - Deep metagenome and metatranscriptome analyses of microbial communities affiliated with an industrial biogas fermenter, a cow rumen, and elephant feces reveal major differences in carbohydrate hydrolysis strategies. AB - BACKGROUND: The diverse microbial communities in agricultural biogas fermenters are assumed to be well adapted for the anaerobic transformation of plant biomass to methane. Compared to natural systems, biogas reactors are limited in their hydrolytic potential. The reasons for this are not understood. RESULTS: In this paper, we show that a typical industrial biogas reactor fed with maize silage, cow manure, and chicken manure has relatively lower hydrolysis rates compared to feces samples from herbivores. We provide evidence that on average, 2.5 genes encoding cellulolytic GHs/Mbp were identified in the biogas fermenter compared to 3.8 in the elephant feces and 3.2 in the cow rumen data sets. The ratio of genes coding for cellulolytic GH enzymes affiliated with the Firmicutes versus the Bacteroidetes was 2.8:1 in the biogas fermenter compared to 1:1 in the elephant feces and 1.4:1 in the cow rumen sample. Furthermore, RNA-Seq data indicated that highly transcribed cellulases in the biogas fermenter were four times more often affiliated with the Firmicutes compared to the Bacteroidetes, while an equal distribution of these enzymes was observed in the elephant feces sample. CONCLUSIONS: Our data indicate that a relatively lower abundance of bacteria affiliated with the phylum of Bacteroidetes and, to some extent, Fibrobacteres is associated with a decreased richness of predicted lignocellulolytic enzymes in biogas fermenters. This difference can be attributed to a partial lack of genes coding for cellulolytic GH enzymes derived from bacteria which are affiliated with the Fibrobacteres and, especially, the Bacteroidetes. The partial deficiency of these genes implies a potentially important limitation in the biogas fermenter with regard to the initial hydrolysis of biomass. Based on these findings, we speculate that increasing the members of Bacteroidetes and Fibrobacteres in biogas fermenters will most likely result in an increased hydrolytic performance. PMID- 27279901 TI - Genome-wide redistribution of MeCP2 in dorsal root ganglia after peripheral nerve injury. AB - BACKGROUND: Methyl-CpG-binding protein 2 (MeCP2), a protein with affinity for methylated cytosines, is crucial for neuronal development and function. MeCP2 regulates gene expression through activation, repression and chromatin remodeling. Mutations in MeCP2 cause Rett syndrome, and these patients display impaired nociception. We observed an increase in MeCP2 expression in mouse dorsal root ganglia (DRG) after peripheral nerve injury. The functional implication of increased MeCP2 is largely unknown. To identify regions of the genome bound by MeCP2 in the DRG and the changes induced by nerve injury, a chromatin immunoprecipitation of MeCP2 followed by sequencing (ChIP-seq) was performed 4 weeks after spared nerve injury (SNI). RESULTS: While the number of binding sites across the genome remained similar in the SNI model and sham control, SNI induced the redistribution of MeCP2 to transcriptionally relevant regions. To determine how differential binding of MeCP2 can affect gene expression in the DRG, we investigated mmu-miR-126, a microRNA locus that had enriched MeCP2 binding in the SNI model. Enriched MeCP2 binding to miR-126 locus after nerve injury repressed miR-126 expression, and this was not mediated by alterations in methylation pattern at the miR-126 locus. Downregulation of miR-126 resulted in the upregulation of its two target genes Dnmt1 and Vegfa in Neuro 2A cells and in SNI model compared to control. These target genes were significantly downregulated in Mecp2-null mice compared to wild-type littermates, indicating a regulatory role for MeCP2 in activating Dnmt1 and Vegfa expression. Intrathecal delivery of miR 126 was not sufficient to reverse nerve injury-induced mechanical and thermal hypersensitivity, but decreased Dnmt1 and Vegfa expression in the DRG. CONCLUSIONS: Our study shows a regulatory role for MeCP2 in that changes in global redistribution can result in direct and indirect modulation of gene expression in the DRG. Alterations in genome-wide binding of MeCP2 therefore provide a molecular basis for a better understanding of epigenetic regulation induced molecular changes underlying nerve injury. PMID- 27279902 TI - High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe. AB - The dismal prognosis of patients with malignant brain tumors such as glioblastoma multiforme (GBM) is attributed mostly to their diffuse growth pattern and early microscopic tumor spread to distant regions of the brain. Because the microscopic tumor foci cannot be visualized with current imaging modalities, it remains impossible to direct treatments optimally. Here we explored the ability of integrin-targeted surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles to depict the true tumor extent in a GBM mouse model that closely mimics the pathology in humans. The recently developed SERRS-nanoparticles have a sensitivity of detection in the femtomolar range. An RGD-peptide-conjugated version for integrin-targeting (RGD-SERRS) was compared directly to its non targeted RAD-SERRS control in the same mice via Raman multiplexing. Pre-blocking with RGD peptide before injection of RGD-SERRS nanoparticles was used to verify the specificity of integrin-targeting. In contrast to the current belief that the enhanced permeability and retention (EPR) effect results in a baseline uptake of nanoparticles regardless of their surface chemistry, integrin-targeting was shown to be highly specific, with markedly lower accumulation after pre-blocking. While the non-targeted SERRS particles enabled delineation of the main tumor, the RGD SERRS nanoparticles afforded a major improvement in visualization of the true extent and the diffuse margins of the main tumor. This included the detection of unexpected tumor areas distant to the main tumor, tracks of migrating cells of 2 3 cells in diameter, and even isolated distant tumor cell clusters of less than 5 cells. This Raman spectroscopy-based nanoparticle-imaging technology holds promise to allow high precision visualization of the true extent of malignant brain tumors. PMID- 27279903 TI - Design of Internalizing PSMA-specific Glu-ureido-based Radiotherapeuticals. AB - Despite the progress in diagnosis and treatment, prostate cancer (PCa) is one of the main causes for cancer-associated deaths among men. Recently, prostate specific membrane antigen (PSMA) binding tracers have revolutionized the molecular imaging of this disease. The translation of these tracers into therapeutic applications is challenging because of high PSMA-associated kidney uptake. While both the tumor uptake and the uptake in the kidneys are PSMA specific, the kidneys show a more rapid clearance than tumor lesions. Consequently, the potential of endoradiotherapeutic drugs targeting PSMA is highly dependent on a sustained retention in the tumor - ideally achieved by predominant internalization of the respective tracer. Previously, we were able to show that the pharmacokinetics of the tracers containing the Glu-urea-based binding motif can be further enhanced with a specifically designed linker. Here, we evaluate an eventual influence of the chelator moiety on the pharmacokinetics, including the tumor internalization. A series of tracers modified by different chelators were synthesized using solid phase chemistry. The conjugates were radiolabeled to evaluate the influence on the receptor binding affinity, the ligand-induced internalization and the biodistribution behavior. Competitive binding and internalization assays were performed on PSMA positive LNCaP cells and the biodistribution of the most promising compound was evaluated by positron emission tomography (PET) in LNCaP-tumor-bearing mice. Interestingly, conjugation of the different chelators did not cause significant differences: all compounds showed nanomolar binding affinities with only minor differences. PET imaging of the (68)Ga-labeled CHX-A''-DTPA conjugate revealed that the chelator moiety does not impair the specificity of tumor uptake when compared to the gold standard PSMA-617. However, strong differences of the internalization ratios caused by the chelator moiety were observed: differences in internalization between 15% and 65% were observed, with the CHX-A''-DTPA conjugate displaying the highest internalization ratio. A first-in-man PET/CT study proved the high tumor uptake of this (68)Ga-labeled PSMA-targeting compound. These data indicate that hydrophobic entities at the chelator mediate the internalization efficacy. Based on its specific tumor uptake in combination with its very high internalization ratio, the clinical performance of the chelator-conjugated Glu-urea-based PSMA inhibitors will be further elucidated. PMID- 27279904 TI - Fabrication of Graphene and AuNP Core Polyaniline Shell Nanocomposites as Multifunctional Theranostic Platforms for SERS Real-time Monitoring and Chemo photothermal Therapy. AB - In this work, novel theranostic platforms based on graphene oxide and AuNP core polyaniline shell (GO-Au@PANI) nanocomposites are fabricated for simultaneous SERS imaging and chemo-photothermal therapy. PANI, a new NIR photothermal therapy agent with strong NIR absorption, outstanding stability and low cytotoxicity is decorated on AuNPs by one-pot oxidative polymerization, then the Au@PANI core shell nanoparticles are attached to the graphene oxide (GO) sheet via pi-pi stacking and electrostatic interaction. The obtained GO-Au@PANI nanohybirds exhibit excellent NIR photothermal transduction efficiency and ultrahigh drug loading capacity. The nanocomposites can also serve as novel NIR SERS probes utilizing the intense SERS signals of PANI. Rapid SERS imaging of cancer cells is achieved using this ultrasensitive nanoprobe. GO-Au@PANI also reveals good capability of drug delivery with the DOX-loading efficiency of 189.2% and sensitive NIR/pH-responsive DOX release. The intracellular real-time drug release dynamics from the nanocomposites is monitored by SERS-fluorescence dual mode imaging. Finally, chemo-photothermal ablation of cancer cells is carried out in vitro and in vivo using GO-Au@PANI as high-performance chemo-photothermal therapeutic nanoagent. The theranostic applications of GO-Au@PANI endow it with great potential for personalized and precise cancer medicine. PMID- 27279905 TI - MiR675-5p Acts on HIF-1alpha to Sustain Hypoxic Responses: A New Therapeutic Strategy for Glioma. AB - Hypoxia is a common feature in solid tumours. In glioma, it is considered the major driving force for tumour angiogenesis and correlates with enhanced resistance to conventional therapies, increased invasiveness and a poor prognosis for patients. Here we describe, for the first time, that miR675-5p, embedded in hypoxia-induced long non-coding RNA H19, plays a mandatory role in establishing a hypoxic response and in promoting hypoxia-mediated angiogenesis. We demonstrated, in vitro and in vivo, that miR675-5p over expression in normoxia is sufficient to induce a hypoxic moreover, miR675-5p depletion in low oxygen conditions, drastically abolishes hypoxic responses including angiogenesis. In addition, our data indicate an interaction of miR675-5p, HIF-1alpha mRNA and the RNA Binding Protein HuR in hypoxia-induced responses. We suggest the modulation of miR675-5p as a new therapeutic option to promote or abolish hypoxia induced angiogenesis. PMID- 27279906 TI - Recapitulating the Size and Cargo of Tumor Exosomes in a Tissue-Engineered Model. AB - There is a growing interest in the pivotal role of exosomes in cancer and in their use as biomarkers. However, despite the importance of the microenvironment for cancer initiation and progression, monolayer cultures of tumor cells still represent the main in vitro source of exosomes. As a result, their environmental regulation remains largely unknown. Here, we report a three-dimensional tumor model for studying exosomes, using Ewing's sarcoma type 1 as a clinically relevant example. The bioengineered model was designed based on the hypothesis that the 3-dimensionality, composition and stiffness of the tumor matrix are the critical determinants of the size and cargo of exosomes released by the cancer cells. We analyzed the effects of the tumor microenvironment on exosomes, and the effects of exosomes on the non-cancer cells from the bone niche. Exosomes from the tissue-engineered tumor had similar size distribution as those in the patients' plasma, and were markedly smaller than those in monolayer cultures. Bioengineered tumors and the patients' plasma contained high levels of the Polycomb histone methyltransferase EZH2 mRNA relatively to their monolayer counterparts. Notably, EZH2 mRNA, a potential tumor biomarker detectable in blood plasma, could be transferred to the surrounding mesenchymal stem cells. This study provides the first evidence that an in vitro culture environment can recapitulate some properties of tumor exosomes. PMID- 27279907 TI - Photodynamic Therapy Induced Enhancement of Tumor Vasculature Permeability Using an Upconversion Nanoconstruct for Improved Intratumoral Nanoparticle Delivery in Deep Tissues. AB - Photodynamic therapy (PDT) has recently emerged as an approach to enhance intratumoral accumulation of nanoparticles. However, conventional PDT is greatly limited by the inability of the excitation light to sufficiently penetrate tissue, rendering PDT ineffective in the relatively deep tumors. To address this limitation, we developed a novel PDT platform and reported for the first time the effect of deep-tissue PDT on nanoparticle uptake in tumors. This platform employed c(RGDyK)-conjugated upconversion nanoparticles (UCNPs), which facilitate active targeting of the nanoconstruct to tumor vasculature and achieve the deep tissue photosensitizer activation by NIR light irradiation. Results indicated that our PDT system efficiently enhanced intratumoral uptake of different nanoparticles in a deep-seated tumor model. The optimal light dose for deep tissue PDT (34 mW/cm(2)) was determined and the most robust permeability enhancement was achieved by administering the nanoparticles within 15 minutes following PDT treatment. Further, a two-step treatment strategy was developed and validated featuring the capability of improving the therapeutic efficacy of Doxil while simultaneously reducing its cardiotoxicity. This two-step treatment resulted in a tumor inhibition rate of 79% compared with 56% after Doxil treatment alone. These findings provide evidence in support of the clinical application of deep-tissue PDT for enhanced nano-drug delivery. PMID- 27279909 TI - Redox Regulation of Stem-like Cells Though the CD44v-xCT Axis in Colorectal Cancer: Mechanisms and Therapeutic Implications. AB - Colorectal cancer (CRC) is a common neoplastic disease and a frequent cause of death. Drug resistance is a major challenge to CRC treatment and stem-like side population (SP) cells may play a key role in this resistance. Although it has been recognized that cancer stem cells may be affected by redox status, the underlying mechanisms for this effect and the roles of celllular redox adaptation and antioxidant capacity in CRC remain elusive. Our study shows that CRC SP cells are highly dependent on cellular GSH to maintain ROS levels below those of non-SP cells. Exposing CRC cells to H2O2 produced a significant decrease in the percentage of SP cells, which was rescued by adding N-acetylcysteine. Mechanistically, CD44v interacts with and stabilizes xCT and thereby promotes the uptake of cysteine for GSH synthesis and stimulates SP cell enrichment. Additionally, miR-1297 levels were inversely correlated with the expression of xCT; thus, reduced miR-1297 contributes to SP cell enrichment in CRC tumors, which results in tumor aggressiveness and poor clinical outcomes. Importantly, redox modification by PEITC significantly reduces CRC SP cells in vitro and impairs tumors growth in vivo. The combination of 5FU and PEITC led to synergistic cytotoxic effects against CRC cells in vitro and in vivo. Taken together, our data suggest that a GSH-mediated reduction in cellular ROS levels is an essential regulator of CRC SP cells mediated by the CD44v-xCT axis, and disrupting the redox status may eliminate the chemotherapy-resistant CRC SP cells with potentially significant benefits for cancer treatment. PMID- 27279908 TI - Synthesis and Preclinical Evaluation of Sulfonamido-based [(11)C-Carbonyl] Carbamates and Ureas for Imaging Monoacylglycerol Lipase. AB - Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4 chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [(11)C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [(11)C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL. PMID- 27279910 TI - Polymer-DNA Nanoparticle-Induced CXCR4 Overexpression Improves Stem Cell Engraftment and Tissue Regeneration in a Mouse Hindlimb Ischemia Model. AB - Peripheral arterial disease affects nearly 202 million individuals worldwide, sometimes leading to non-healing ulcers or limb amputations in severe cases. Genetically modified stem cells offer potential advantages for therapeutically inducing angiogenesis via augmented paracrine release mechanisms and tuned dynamic responses to environmental stimuli at disease sites. Here, we report the application of nanoparticle-induced CXCR4-overexpressing stem cells in a mouse hindlimb ischemia model. We found that CXCR4 overexpression improved stem cell survival, modulated inflammation in situ, and accelerated blood reperfusion. These effects, unexpectedly, led to complete limb salvage and skeletal muscle repair, markedly outperforming the efficacy of the conventional angiogenic factor control, VEGF. Importantly, assessment of CXCR4-overexpressing stem cells in vitro revealed that CXCR4 overexpression induced changes in paracrine signaling of stem cells, promoting a therapeutically desirable pro-angiogenic and anti inflammatory phenotype. These results suggest that nanoparticle-induced CXCR4 overexpression may promote favorable phenotypic changes and therapeutic efficacy of stem cells in response to the ischemic environment. PMID- 27279911 TI - Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes. AB - New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the alpha2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the alpha2,3 sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic. PMID- 27279912 TI - Gas6/Axl Axis Contributes to Chemoresistance and Metastasis in Breast Cancer through Akt/GSK-3beta/beta-catenin Signaling. AB - Chemoresistance in breast cancer has been of great interest in past studies. However, the development of rational therapeutic strategies targeting chemoresistant cells is still a challenge in clinical oncology. By integrating data from global differences of gene expression and phospho-receptor tyrosine kinases between sensitive parental cells (MCF-7) and doxorubicin-resistant cells (MCF-7/ADR), we identified Axl as a potential target for chemoresistance and metastasis in multidrug resistant breast cancer cells. We analyzed Axl expression in 57 breast cancer cell lines and detected a dramatic increase in its expression level in mesenchymal breast cancer cell lines. Axl silencing suppressed invasive and metastatic potentials of chemoresistant breast cancer cells as well as increased elimination of cancer cells when combined with doxorubicin. Furthermore, in preclinical assays, an Axl inhibitor R428 showed increased cell death upon doxorubicin treatment. Additionally, using phospho-kinase array based proteomic analysis, we identified that Akt/GSK-3beta/beta-catenin cascade was responsible for Axl-induced cell invasion. Nuclear translocation of beta-catenin then induced transcriptional upregulation of ZEB1, which in turn regulated DNA damage repair and doxorubicin-resistance in breast cancer cells. Most importantly, Axl was correlated with its downstream targets in tumor samples and was associated with poor prognosis in breast cancer patients. These results demonstrate that Gas6/Axl axis confers aggressiveness in breast cancer and may represent a therapeutic target for chemoresistance and metastasis. PMID- 27279913 TI - (18)F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy. AB - Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. (11)C PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, (18)F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE. This study was divided into two parts. The first part compared (18)F-DPA-714 and (11)C-PK11195 radiotracers in ten HE induced rats [bile duct ligation (BDL) and fed hyperammonemic diet (HD)] and 6 control rats. The animal subjects underwent dynamic positron emission tomography (PET) during 2-day intervals. The (11)C-PK11195 PET study showed no differences in whole brain average percent injected dose per gram (%ID/g) values at all time points (all P>0.05), while the (18)F-DPA-714 PET study showed higher whole brain average %ID/g values in HE rats compared to control group rats at 900 s to 3300 s after injecting radiotracer (all P<0.05). The second part of the study evaluated the effectiveness of ibuprofen (IBU) treatment to chronic HE. Forty rats were classified into six groups, including Sham+normal saline (NS), Sham+IBU, BDL+NS, BDL+HD+NS, BDL+IBU, and BDL+HD+IBU groups. (18)F-DPA-714 PET was used to image neuroinflammation. Whole and regional brain average %ID/g values, neurological features, inflammatory factors and activated microglia showed better in the IBU groups than in the NS groups (all P<0.05) and no difference was seen in the Sham groups compared to IBU groups (all P>0.05). In conclusion, this study demonstrated that (18)F-DPA-714 is an ideal TPSO radiotracer for imaging neuroinflammation and monitoring anti-neuroinflammation treatment efficacy of chronic HE. PMID- 27279914 TI - Adaptive and Acquired Resistance to EGFR Inhibitors Converge on the MAPK Pathway. AB - Both adaptive and acquired resistance significantly limits the efficacy of the epidermal growth factor receptor (EGFR) kinase inhibitors. However, the distinct or common mechanisms of adaptive and acquired resistance have not been fully characterized. Here, through systematic modeling of erlotinib resistance in lung cancer, we found that feedback reactivation of MAPK signaling following erlotinib treatment, which was dependent on the MET receptor, contributed to the adaptive resistance of EGFR inhibitors. Interestingly, acquired resistance to erlotinib was also associated with the MAPK pathway activation as a result of CRAF or NRAS amplification. Consequently, combined inhibition of EGFR and MAPK impeded the development of both adaptive and acquired resistance. These observations demonstrate that adaptive and acquired resistance to EGFR inhibitors can converge on the same pathway and credential cotargeting EGFR and MAPK as a promising therapeutic approach in EGFR mutant tumors. PMID- 27279915 TI - Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity. AB - Increased cholinergic activity has been highlighted in the pathogenesis of airway hyperresponsiveness, and alternations of mitochondrial structure and function appear to be involved in many lung diseases including airway hyperresponsiveness. It is crucial to clarify the cause-effect association between mitochondrial dysfunction and cholinergic hyperactivity in the pathogenesis of airway hyperresponsiveness. Male SD rats and cultured airway epithelial cells were exposed to cigarette smoke plus lipopolysaccharide administration; mitochondria isolated from airway epithelium were delivered into epithelial cells in vitro and in vivo. Both the cigarette smoke plus lipopolysaccharide-induced cholinergic hyperactivity in vitro and the airway hyperresponsiveness to acetylcholine in vivo were reversed by the transplantation of exogenous mitochondria. The rescue effects of exogenous mitochondria were imitated by the elimination of excessive reactive oxygen species or blockage of muscarinic M3 receptor, but inhibited by M receptor enhancer. Mitochondrial transplantation effectively attenuates cigarette smoke plus lipopolysaccharide-stimulated airway hyperresponsiveness through the inhibition of ROS-enhanced epithelial cholinergic hyperactivity. PMID- 27279917 TI - Coming full circle - introducing the Multinational Time Use Study Simple File. PMID- 27279916 TI - HER2 Targeting Peptides Screening and Applications in Tumor Imaging and Drug Delivery. AB - Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor 2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery. PMID- 27279921 TI - Peripheral blood methylation profiling of female Crohn's disease patients. AB - BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder belonging to the inflammatory bowel diseases (IBD). CD affects distinct parts of the gastrointestinal tract, leading to symptoms including diarrhea, fever, abdominal pain, weight loss, and anemia. The aim of this study was to assess whether the DNA methylome of peripheral blood cells can be associated with CD in women. METHODS: Samples were obtained from 18 female patients with histologically confirmed ileal or ileocolic CD and 25 healthy age- and gender-matched controls (mean age and standard deviation: 30.5 +/- 6.5 years for both groups). Genome wide DNA methylation was determined using the Illumina HumanMethylation 450k BeadChip. RESULTS: Our analysis implicated 4287 differentially methylated positions (DMPs; corrected p < 0.05) that are associated to 2715 unique genes. Gene ontology enrichment analysis revealed significant enrichment of our DMPs in immune response processes and inflammatory pathways. Of the 4287 DMPs, 32 DMPs were located on chromosome X with several hits for MIR223 and PABPC5. Comparison with previously performed (epi)genome-wide studies revealed that we replicated 33 IBD-associated genes. In addition to DMPs, we found eight differentially methylated regions (DMRs). CONCLUSIONS: CD patients display a characteristic DNA methylation landscape, with the differentially methylated genes being implicated in immune response. Additionally, DMPs were found on chromosome X suggesting X linked manifestations of CD that could be associated with female-specific symptoms. PMID- 27279922 TI - Validity and Reliability of the Attachment Insecurity Screening Inventory (AISI) 2-5 Years. AB - The Attachment Insecurity Screening Inventory (AISI) 2-5 years is a parent-report questionnaire for assessing attachment insecurity in preschoolers. Validity and reliability of the AISI 2-5 years were examined in a general sample (n = 429) and in a clinical sample (n = 71). Confirmatory factor analysis (CFA) confirmed a three-factor model of avoidant, ambivalent/resistant and disorganized attachment, and one higher-order factor of total attachment insecurity. Multi-group CFA indicated measurement invariance across mothers and fathers, and across the general and clinical population sample. Reliability coefficients were generally found to be good. We found partial support for convergent validity in associations between AISI-scores and observed attachment (AQS). Concurrent validity was supported by associations between AISI-scores and observed parental sensitivity (MBQS) and parent-reported psychopathology (SDQ). Finally, the AISI discriminated well between children from the general and from the clinical sample. We argue that both research and practice could benefit from the AISI as there is now a prospect of quickly, reliably and validly screening for attachment insecurity in pre-school aged children. Based on this information, help can be offered timely and, subsequently, the prevention of attachment related problems of children can be strengthened. PMID- 27279923 TI - Identification of eight novel SDHB, SDHC, SDHD germline variants in Danish pheochromocytoma/paraganglioma patients. AB - BACKGROUND: Germline mutations in the succinate dehydrogenase complex genes SDHB, SDHC, and SDHD predispose to pheochromocytomas and paragangliomas. Here, we examine the SDHB, SDHC, and SDHD mutation spectrum in the Danish population by screening of 143 Danish pheochromocytoma and paraganglioma patients. METHODS: Mutational screening was performed by Sanger sequencing or next-generation sequencing. The frequencies of variants of unknown clinical significance, e.g. intronic, missense, and synonymous variants, were determined using the Exome Aggregation Consortium database, while the significance of missense mutations was predicted by in silico and loss of heterozygosity analysis when possible. RESULTS: We report 18 germline variants; nine in SDHB, six in SDHC, and three in SDHD. Of these 18 variants, eight are novel. We classify 12 variants as likely pathogenic/pathogenic, one as likely benign, and five as variants of unknown clinical significance. CONCLUSIONS: Identifying and classifying SDHB, SDHC, and SDHD variants present in the Danish population will augment the growing knowledge on variants in these genes and may support future clinical risk assessments. PMID- 27279924 TI - Myxomatous Mitral Valve with Prolapse and Flail Scallop. AB - BACKGROUND: Myxomatous mitral valve with prolapse are classically seen with abnormal leaflet apposition during contraction of the heart. Hemodynamic disorders can result from eccentric mitral regurgitation usually caused by chordae tendinae rupture or papillary muscle dysfunction. Echocardiography is the gold standard for evaluation of leaflet flail and prolapse due to high sensitivity and specificity. Though most mitral valve prolapse are asymptomatic those that cause severe regurgitation need emergent surgical intervention to prevent disease progression. CASE REPORT: We report a 54 year old Hispanic male who presented with progressively worsening dyspnea and palpitations. Initial evaluation was significant for atrial fibrillation on electrocardiogram with subsequent echocardiography revealing myxomatous mitral valve with prolapse. Following surgical repair of the mitral valve, the dyspnea and palpitations resolved. CONCLUSIONS: Mitral valve prolapse is a common valvular abnormality but the pathogenic cause of myxomatous valves has not been elucidated. Several theories describe multiple superfamilies of proteins to be involved in the process. Proper identification of these severe mitral regurgitation due to these disease valves will help relieve symptomatic mitral valve prolapse patients. PMID- 27279925 TI - Contrast Intravasation During Hysterosalpingography. AB - Hysterosalpingography is an imaging method to evaluate the endometrial and uterine morphology and fallopian tube patency. Contrast intravasation implies backflow of injected contrast into the adjoining vessels mostly the veins and may be related to factors altering endometrial vascularity and permeability. Radiologists and gynaecologists should be well acquainted with the technique of hysterosalpingography, its interpretation, and intravasation of contrast agents for safer procedure and to minimize the associated complications. PMID- 27279926 TI - Use of Ultrasound Elastography in the Assessment of the Musculoskeletal System. AB - This article presents possible applications of ultrasound elastography in musculoskeletal imaging based on the available literature, as well as the possibility of extending indications for the use of elastography in the future. Ultrasound elastography (EUS) is a new method that shows structural changes in tissues following application of physical stress. Elastography techniques have been widely used to assess muscles and tendons in vitro since the early parts of the twentieth century. Only recently with the advent of new technology and creation of highly specialized ultrasound devices, has elastography gained widespread use in numerous applications. The authors performed a search of the Medline/PubMed databases for original research and reviewed publications on the application of ultrasound elastography for musculoskeletal imaging. All publications demonstrate possible uses of ultrasound elastography in examinations of the musculoskeletal system. The most widely studied areas include the muscles, tendons and rheumatic diseases. There are also reports on the employment in vessel imaging. The main limitation of elastography as a technique is above all the variability of applied pressure during imaging, which is operator-dependent. It would therefore be reasonable to provide clear guidelines on the technique applied, as well as clear indications for performing the test. It is important to develop methods for creating artifact-free, closed-loop, compression decompression cycles. The main advantages include cost-effectiveness, short duration of the study, non-invasive nature of the procedure, as well as a potentially broader clinical availability. There are no clear guidelines with regard to indications as well as examination techniques. Ultrasound elastography is a new and still poorly researched method. We conclude, however, that it can be widely used in the examinations of musculoskeletal system. Therefore, it is necessary to conduct large, multi-center studies to determine the methodology, indications and technique of examination. PMID- 27279927 TI - Hyperdense Middle Cerebral Artery Sign Together with Pulmonary Thromboembolism. AB - BACKGROUND: Hyperdense middle cerebral artery sign is an appearance of the middle cerebral artery on non-contrast-enhanced computed tomography. Embolic occlusion of the pulmonary arterial system is referred to as pulmonary embolism. When pulmonary embolism coexists with a patent foramen ovale, increased pressure in the right atrium may result in widening of the foramen and consequently, cause serious conditions due to paradoxical embolus. Coexistence of hyperdense middle cerebral artery sign and pulmonary thromboembolism is very rare in the literature. CASE REPORT: We presented a 60-year-old female patient who had both hyperdense middle cerebral artery sign and pulmonary thromboembolism. CONCLUSIONS: To our knowledge, togetherness of hyperdense MCA sign and pulmonary thromboembolism is extremely rare in the literature. In our case, we found both pulmonary embolism due to DVT and paradoxical embolism due to existing patent foramen ovale. PMID- 27279928 TI - Skin Testing for Allergic Rhinitis: A Health Technology Assessment. AB - BACKGROUND: Allergic rhinitis is the most common type of allergy worldwide. The accuracy of skin testing for allergic rhinitis is still debated. This health technology assessment had two objectives: to determine the diagnostic accuracy of skin-prick and intradermal testing in patients with suspected allergic rhinitis and to estimate the costs to the Ontario health system of skin testing for allergic rhinitis. METHODS: We searched All Ovid MEDLINE, Embase, and Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, CRD Health Technology Assessment Database, Cochrane Central Register of Controlled Trials, and NHS Economic Evaluation Database for studies that evaluated the diagnostic accuracy of skin-prick and intradermal testing for allergic rhinitis using nasal provocation as the reference standard. For the clinical evidence review, data extraction and quality assessment were performed using the QUADAS-2 tool. We used the bivariate random-effects model for meta-analysis. For the economic evidence review, we assessed studies using a modified checklist developed by the (United Kingdom) National Institute for Health and Care Excellence. We estimated the annual cost of skin testing for allergic rhinitis in Ontario for 2015 to 2017 using provincial data on testing volumes and costs. RESULTS: We meta-analyzed seven studies with a total of 430 patients that assessed the accuracy of skin-prick testing. The pooled pair of sensitivity and specificity for skin-prick testing was 85% and 77%, respectively. We did not perform a meta-analysis for the diagnostic accuracy of intradermal testing due to the small number of studies (n = 4). Of these, two evaluated the accuracy of intradermal testing in confirming negative skin-prick testing results, with sensitivity ranging from 27% to 50% and specificity ranging from 60% to 100%. The other two studies evaluated the accuracy of intradermal testing as a stand-alone tool for diagnosing allergic rhinitis, with sensitivity ranging from 60% to 79% and specificity ranging from 68% to 69%. We estimated the budget impact of continuing to publicly fund skin testing for allergic rhinitis in Ontario to be between $2.5 million and $3.0 million per year. CONCLUSIONS: Skin-prick testing is moderately accurate in identifying subjects with or without allergic rhinitis. The diagnostic accuracy of intradermal testing could not be well established from this review. Our best estimate is that publicly funding skin testing for allergic rhinitis costs the Ontario government approximately $2.5 million to $3.0 million per year. PMID- 27279930 TI - Tunable in-situ electro-polymerization of hydrogel films for microchip-based bioanalysis. AB - Electro-polymerization phenomena have been previously investigated at the macroscale in the context of producing polymeric coatings over extended surface areas. But electrical actuation also offers exquisite local control of the polymerized films' position, morphology, and thickness, suggesting compelling advantages in microfluidic-based analysis systems. Here, we introduce a microfabricated platform incorporating arrays of individually addressable on-chip electrodes capable of generating discretely positioned electro-polymerized hydrogel films inside microchannels in timescales of ~5 min. Sequential actuation of specific electrode pairs initiates localized propagation of anchored polyacrylamide gel films and permits directed control of their size, shape, and growth rate. In addition to precise positioning of hydrogel films, obstacles, and barriers within microchannel networks, our approach makes it possible to encapsulate macromolecules within the films during polymerization, suggesting utility in a host of areas including separations, sample purification, and immunoassays. PMID- 27279929 TI - A modified random walk door-to-door recruitment strategy for collecting social and biological data relating to mental health, substance use, addiction, and violence problems in a Canadian community. AB - AIMS: To describe a modified "random walk" door-to-door recruitment strategy used to obtain a random community sample for participation in a study relating to mental health, substance use, addiction, and violence (MSAV) problems and involving the collection of both self-report and biological (hair and saliva) data. This paper describes study protocols, response rates for the study and for the provision of biological data, and possible further applications for this data collection method. DESIGN: A two-stage cluster sample was derived from the 2006 Canadian census sampling frame for a small Ontario community, based on the random selection of city blocks as the primary sampling units and households as the secondary sampling units. SETTING: A small city in Ontario, Canada. PARTICIPANTS: A general population sample of 92 participants selected randomly from households using Kish tables. MEASURES: A computerized questionnaire was administered to obtain self-report data on MSAV problems. Saliva was collected to study genetic vulnerabilities to MSAV problems, and hair was collected to examine stress levels (via the hormone cortisol) as they relate to MSAV problems. FINDINGS: The study showed a response rate of 50% and a high rate of provision of biological samples (over 95%). CONCLUSIONS: Modified random walk methodologies involving face-to face recruitment may represent a useful approach for obtaining general population samples for studies of MSAV problems, particularly those involving the collection of biological samples. Further studies are needed to assess whether this approach leads to better response rates and improved estimates compared to other survey methods used in research on substance use. PMID- 27279931 TI - Microfluidics made easy: A robust low-cost constant pressure flow controller for engineers and cell biologists. AB - Over the last decade, microfluidics has become increasingly popular in biology and bioengineering. While lab-on-a-chip fabrication costs have continued to decrease, the hardware required for delivering controllable fluid flows to the microfluidic devices themselves remains expensive and often cost prohibitive for researchers interested in starting a microfluidics project. Typically, microfluidic experiments require precise and tunable flow rates from a system that is simple to operate. While many labs use commercial platforms or syringe pumps, these solutions can cost thousands of dollars and can be cost prohibitive. Here, we present an inexpensive and easy-to-use constant pressure system for delivering flows to microfluidic devices. The controller costs less than half the price of a single syringe pump but can independently switch and deliver fluid through up to four separate fluidic inlets at known flow rates with significantly faster fluid response times. It is constructed of readily available pressure regulators, gauges, plastic connectors and adapters, and tubing. Flow rate is easily predicted and calibrated using hydraulic circuit analysis and capillary tubing resistors. Finally, we demonstrate the capabilities of the flow system by performing well-known microfluidic experiments for chemical gradient generation and emulsion droplet production. PMID- 27279932 TI - Humidity assay for studying plant-pathogen interactions in miniature controlled discrete humidity environments with good throughput. AB - This paper reports a highly economical and accessible approach to generate different discrete relative humidity conditions in spatially separated wells of a modified multi-well plate for humidity assay of plant-pathogen interactions with good throughput. We demonstrated that a discrete humidity gradient could be formed within a few minutes and maintained over a period of a few days inside the device. The device consisted of a freeway channel in the top layer, multiple compartmented wells in the bottom layer, a water source, and a drying agent source. The combinational effects of evaporation, diffusion, and convection were synergized to establish the stable discrete humidity gradient. The device was employed to study visible and molecular disease phenotypes of soybean in responses to infection by Phytophthora sojae, an oomycete pathogen, under a set of humidity conditions, with two near-isogenic soybean lines, Williams and Williams 82, that differ for a Phytophthora resistance gene (Rps1-k). Our result showed that at 63% relative humidity, the transcript level of the defense gene GmPR1 was at minimum in the susceptible soybean line Williams and at maximal level in the resistant line Williams 82 following P. sojae CC5C infection. In addition, we investigated the effects of environmental temperature, dimensional and geometrical parameters, and other configurational factors on the ability of the device to generate miniature humidity environments. This work represents an exploratory effort to economically and efficiently manipulate humidity environments in a space-limited device and shows a great potential to facilitate humidity assay of plant seed germination and development, pathogen growth, and plant-pathogen interactions. Since the proposed device can be easily made, modified, and operated, it is believed that this present humidity manipulation technology will benefit many laboratories in the area of seed science, plant pathology, and plant-microbe biology, where humidity is an important factor that influences plant disease infection, establishment, and development. PMID- 27279933 TI - Micro electrical impedance spectroscopy on a needle for ex vivo discrimination between human normal and cancer renal tissues. AB - The ex-vivo discrimination between human normal and cancer renal tissues was confirmed using MUEoN (micro electrical impedance spectroscopy-on-a-needle) by measuring and comparing the electrical impedances in the frequency domain. To quantify the extent of discrimination between dissimilar tissues and to determine the optimal frequency at which the discrimination capability is at a maximum, discrimination index (DI) was employed for both magnitude and phase. The highest values of DI for the magnitude and phase were 5.15 at 1 MHz and 3.57 at 1 kHz, respectively. The mean magnitude and phase measured at the optimal frequency for normal tissues were 5013.40 +/- 94.39 Omega and -68.54 +/- 0.72 degrees , respectively; those for cancer tissues were 4165.19 +/- 70.32 Omega and -64.10 +/ 0.52 degrees , respectively. A statistically significant difference (p< 0.05) between the two tissues was observed at all the investigated frequencies. To extract the electrical properties (resistance and capacitance) of these bio tissues through curve fitting with experimental results, an equivalent circuit was proposed based on the MUEoN structure on the condition that the MUEoN was immersed in the bio-tissues. The average and standard deviation of the extracted resistance and capacitance for the normal tissues were 6.22 +/- 0.24 kOmega and 280.21 +/- 32.25 pF, respectively, and those for the cancer tissues were 5.45 +/- 0.22 kOmega and 376.32 +/- 34.14 pF, respectively. The electrical impedance was higher in the normal tissues compared with the cancer tissues. The MUEoN could clearly discriminate between normal and cancer tissues by comparing the results at the optimal frequency (magnitude and phase) and those of the curve fitting (extracted resistance and capacitance). PMID- 27279934 TI - Enhancement of continuous-flow separation of viable/nonviable yeast cells using a nonuniform alternating current electric field with complex spatial distribution. AB - The variability in cell response to AC electric fields is selective enough to separate not only the cell types but also the activation states of similar cells. In this work, we use dielectrophoresis (DEP), which exploits the differences in the dielectric properties of cells, to separate nonviable and viable cells. A parallel-plate DEP device consisting of a bottom face with an array of micro fabricated interdigitated electrodes and a top face with a plane electrode was proposed to facilitate the separation of cells by creating a nonuniform electric field throughout the flow channel. The operation and performance of the device were evaluated using live and dead yeast cells as model biological particles. Further, numerical simulations were conducted for the cell suspensions flowing in a channel with a nonuniform AC electric field, modeled on the basis of the equation of motion of particles, to characterize the separation efficiency by changing the frequency of applied AC voltage. Results demonstrated that dead cells traveling through the channel were focused onto a site around the minimum electric field gradient in the middle of the flow stream, while live cells were trapped on the bottom face. Cells were thus successfully separated under the appropriately tuned frequency of 1 MHz. Predictions showed good agreement with the observation. The proposed DEP device provides a new approach to, for instance, hematological analysis or the separation of different cancer cells for application in circulating tumor cell identification. PMID- 27279935 TI - A dual-core double emulsion platform for osmolarity-controlled microreactor triggered by coalescence of encapsulated droplets. AB - Droplet-based microfluidics has provided a means to generate multi-core double emulsions, which are versatile platforms for microreactors in materials science, synthetic biology, and chemical engineering. To provide new opportunities for double emulsion platforms, here, we report a glass capillary microfluidic approach to first fabricate osmolarity-responsive Water-in-Oil-in-Water (W/O/W) double emulsion containing two different inner droplets/cores and to then trigger the coalescence between the encapsulated droplets precisely. To achieve this, we independently control the swelling speed and size of each droplet in the dual core double emulsion by controlling the osmotic pressure between the inner droplets and the collection solutions. When the inner two droplets in one W/O/W double emulsion swell to the same size and reach the instability of the oil film interface between the inner droplets, core-coalescence happens and this coalescence process can be controlled precisely. This microfluidic methodology enables the generation of highly monodisperse dual-core double emulsions and the osmolarity-controlled swelling behavior provides new stimuli to trigger the coalescence between the encapsulated droplets. Such swelling-caused core coalescence behavior in dual-core double emulsion establishes a novel microreactor for nanoliter-scale reactions, which can protect reaction materials and products from being contaminated or released. PMID- 27279936 TI - DNA hydrogel microspheres and their potential applications for protein delivery and live cell monitoring. AB - Microfluidic devices have been extensively developed as methods for microscale materials fabrication. It has also been adopted for polymeric microsphere fabrication and in situ drug encapsulation. Here, we employed multi-inlet microfluidic channels for DNA hydrogel microsphere formation and in situ protein encapsulation. The release of encapsulated proteins from DNA hydrogels showed different profiles accordingly with the size of microspheres. PMID- 27279937 TI - [Giant cell tumor of the proximal femur treated with total hip arthroplasty]. PMID- 27279938 TI - [Trochanteric tuberculosis, an often difficult diagnosis]. AB - Trochanteric tuberculosis is a rare disease (<2% of osteoarticular tuberculosis), even in high-endemic countries. It is characterized by insidious symptoms. For this reason, diagnosis is often delayed. The authors report a series of 9 cases, the diagnosis was made by bacteriological and histological examinations after imaging assessment (ultrasound, MRI, CT scan). The treatment of this disease is medical (anti-tuberculous antibiotic). Surgical treatment is usually reserved for complications and improves disease progression. PMID- 27279939 TI - [Predictors of malignancy in the management of parotid tumors: about 76 cases]. AB - Salivary gland tumor pathology is complex and poses a diagnostic and therapeutic problem. A good analysis of predictive factors for malignancy in parotid tumors seems currently necessary for better therapeutic planning. The aim of this study was to investigate the predictive factors for malignancy in parotid tumors through a retrospective study of 76 cases of parotid tumor treated in a service of Otorhinolaryngology and Cervico Facial Surgery of Avicenne military hospital of Marrakech between January 2000 and December 2012. The study involved 40 women and 36 men. The average age was 44 years for benign tumours whereas it was 50 years for malignant tumours. The median of consultation time was 24 months for benign tumors and 16 month for malignant tumours. Swelling in the area of the parotid was always a patient detecting sign. Malignancy is clinically suspected based on pain, facial paralysis, surface structure and deeper structure fixity and on the presence of adenopathy. MRI has become the methodology of choice for evaluating parotid tumors due to its good diagnostic value in the assessment of benignity and malignancy. Fine needle aspiration biopsy has no value unless it is positive. Explorative parotidectomy with extemporaneous anatomopathological examination remains the key to positive diagnosis. Parotid benign tumors represent the most frequent entity (80%) and pleomorphic adenoma remains the predominant histologic type (61%). With regard to malignant tumors, they are rare, mainly dominated by mucoepidermoid carcinomas (6,5%). Surgical treatment is the first choice and it is often associated with lymph node dissection and radiation therapy for malignant tumors. Facial paralysis is the most common complication of parotid surgery. PMID- 27279941 TI - [Frequency and Maternals risk factors of foetal intra uterin death at Kamina, Democratic Republic of Congo]. AB - INTRODUCTION: Fetal intrauterine death constitutes a frequent problem in obstetric practice. The objectives of this study were to determine the frequency and to identify risk factors of fetal death at Reference General Hospital of Kamina. METHODS: The study was done in two times. First, a cross-sectional descriptive study of 379 deliveries which allowed to determine the frequency of fetal death. Then, the determination of risk factors was made using a case control study in which the characteristics of 53 fetal deaths were compared to 106 controls constituted of live births. RESULTS: The fetal intrauterine death's frequency at Reference General Hospital of Kamina was at 13,98%. After adjustment, maternal age over 35 years (OR = 6,23; IC= (1,30-29,80)), antecedent of fetal intrauterine death (OR = 3,13; IC= (1,06-9,27)) and diseases during pregnancy (OR = 31,6, IC= [7,66-130,71]) have been identified as factors significantly associated with increased occurrence fetal death. The high maternal education (OR = 0,11; IC= (0,03-0,42)) and Kamina's residency (OR = 0,23; IC= (0,08-0,62)) decreased this risk. CONCLUSION: The frequency of fetal death was 13,9%. The advanced maternal age, the history of fetal death and disease during pregnancy was associated with fetal intra uterin death but the high maternal instruction and the Kamina residence reduced the risk. The monitoring of at-risk pregnant, screening and the treatment of diseases during pregnancy are necessary in view of reducing prevalence of fetal death in our midst. PMID- 27279940 TI - Determination of dichlorvos residue levels in vegetables sold in Lusaka, Zambia. AB - INTRODUCTION: Small scale and large scale farmers around Lusaka, the capital city of Zambia grow vegetables using intensive agriculture methods to satisfy the ever increasing demand. To ensure maximum yield they apply various types of pesticides to control pests and diseases that attack these vegetables. Organophosphate pesticides are widely used in agriculture for the control of various insect pests mainly in developing countries. The purpose of the study was to determine the residual levels of the most commonly used organophosphate, 2, 2-Dichlorovinyl dimethyl phosphate, in three commonestvegetables supplied at various markets around Lusaka. METHODS: Samples of 9 bunches of rape, 14 bunches lettuce and 15 rolls cabbage were randomly picked from several study sites around Lusaka. The vegetables were chopped into small pieces which were chemically treated to get methanol extracts. The extracts were then dissolved in an appropriate solvent and using Shimadzu High Performance Liquid Chromatography-Ultra-violet detector (HPLC UV) levels of 2, 2-Dichlorovinyl dimethyl phosphate were determined. RESULTS: The analysis showed that the average levels of dichlorvos were significantly above the maximum accepted limit as set by Zambian Food and Drugs Act on vegetables. CONCLUSION: Locally grown vegetables from around Lusaka have higher than maximum acceptable limits. This may have implications on human health as the cumulative effect of organophosphates in human body has potential to cause long term health problems. PMID- 27279942 TI - The first cardioverter defibrillator implanted in Central Africa. AB - Sudden cardiac deaths, which account for approximately 350 000 deaths each year, is a major health care problem. Antiarrhythmic drugs have not been reliable in preventing sudden cardiac death. Although beta-blockers, angiotensin-converting enzyme inhibitors, and revascularization play a role in prevention of sudden cardiac death, the development and subsequent refinement of the implantable cardioverter-defibrillator has made the most important contribution to its management. We report the first documented implantation of a cardioverter defibrillator in central, eastern and western Africa. PMID- 27279943 TI - Analysis of Culex and Aedes mosquitoes in southwestern Nigeria revealed no West Nile virus activity. AB - INTRODUCTION: Amplification and transmission of West Nile virus (WNV) by mosquitoes are driven by presence and number of viraemic/susceptible avian hosts. METHODS: In order to predict risk of WNV infection to humans, we collected mosquitoes from horse stables in Lagos and Ibadan, southwestern Nigeria. The mosquitoes were sorted and tested in pools with real-time RT-PCR to detect WNV (or flavivirus) RNA using WNV-specific primers and probes, as well as, pan flavivirus-specific primers in two-step real-time RT-PCR. Minimum infection rate (MIR) was used to estimate mosquito infection rate. RESULTS: Only two genera of mosquitoes were caught (Culex, 98.9% and Aedes, 1.0%) totalling 4,112 females. None of the 424 mosquito pools tested was positive for WNV RNA; consequently the MIR was zero. Sequencing and BLAST analysis of amplicons detected in pan flavivirus primer-mediated RT-PCR gave a consensus sequence of 28S rRNA of Culex quinquefasciatus suggesting integration of flaviviral RNA into mosquito genome. CONCLUSION: While the latter finding requires further investigation, we conclude there was little or no risk of human infection with WNV in the study areas during sampling. There was predominance of Culex mosquito, a competent WNV vector, around horse stables in the study areas. However, mosquito surveillance needs to continue for prompt detection of WNV activity in mosquitoes. PMID- 27279944 TI - A rare case of dermatomyositis revealed during pregnancy with good outcome. AB - There are only few case reports in the literature documenting outcome of pregnancy in patients with DM in contrast with those of other connective tissue diseases especially when dermatomyositis is revealed during pregnancy, most of the publications reported a poor prognosis for both the mother and the fetus, yet, in our case we confirmed the results of the rare recent cases that have tended to show a good outcome, after the treatment with glucocorticoid and immunosuppressant therapy. PMID- 27279945 TI - Condom use and associated factors among men who have sex with men in Togo, West Africa. AB - INTRODUCTION: In 2011, the prevalence of HIV among men who have sex with men (MSM) in Togo was estimated at 19.6% compared to 3.4% in the general population. This study aimed to describe condom use and associated factors among MSM in Togo. METHODS: In 2011, a cross-sectional survey was conducted using the snowball sampling method among MSM in Togo. This study enrolled MSM aged 18 years and above who reported having sexual contact with other men within the last 30 days. A standardized survey form was used for data collection, and multivariate analyses were performed. RESULTS: A total of 724 MSM were included in this study. The median age was 25 years [22-28], 90.3% had at least a secondary school level. The sexual practices during the last sexual encounter with another man included: insertive anal sex (62.2%), receptive anal sex (56.6%), oral sex (33.8%) and oral anal sex (8.6%). A condom was used during the last insertive and receptive anal encounters in 78.4% and 81.2% of the time, respectively. In multivariate analysis, condom use was positively associated with previous participation in HIV/STD prevention activities (aOR=1.72; 95% CI=[1.09-2.71]), with the consideration of the last sexual partner as a casual one (aOR=1.87; 95% CI=[1.24 2.82]) and with having at least a secondary school level (aOR=2.40; 95% CI=[1.22 4.69]). CONCLUSION: One out of five MSM did not use a condom during the last anal encounter with another man. HIV prevention programs in Africa should develop specific interventions targeting MSM to reduce the incidence of HIV in this hidden population. PMID- 27279946 TI - A case of bilateral visual loss after spinal cord surgery. AB - Visual loss is a rare but potentially devastating postoperative complication of prone spinal surgery with a reported incidence of 0.017 to 0.1 percent. We present a case of post-operative bilateral visual loss in a patient who had a laminectomy in prone position under general anesthesia. A 17-year-old male patient with large syringomyelia extending from C2 - T2 level had a surgical procedure done under general anesthesia (GA) in prone position that lasted four hours. After the surgical procedure, the patient presented to the Ophthalmology Clinic of Princess Marina Hospital, with a complaint of visual loss of the right eye followed by left, of one week duration. The patient never had a visual impairment in the past. Physical examination, fundal examination and CT scan revealed no primary cause for the visual loss. In this patient the absence of any finding in the optic disc and the retina and the normal CT scan, suggests that the most likely diagnosis is posterior ischemic optic neuropathy. The patient was treated with prednisolone tablet daily and showed mild improvement in vision. PMID- 27279947 TI - Cerebral venous thrombosis revealing an ulcerative colitis. AB - Cerebral venous thrombosis (CVT) has been reported as an uncommon and devastating complication of ulcerative colitis (UC), with an annual incidence varying between 0,5 to 6,7%. It is suspected to be a consequence of the hypercoagulable state occurring during disease relapse. We report a case of 22-year-old female patient presenting with CVT revealing an UC. Our case raises the awareness among health professionals about the inflammatory bowel diseases (IBD) as a rare etiology of CVT, and signifies the importance of considering antithrombotic prophylaxis in all hospitalised IBD patients, especially those with active disease. PMID- 27279948 TI - End of the Ebola virus outbreak: time to reinforce the African health system and improve preparedness capacity. PMID- 27279949 TI - [An original revealing mode of sarcoidosis: Sweet's syndrome]. AB - Sweet's syndrome is a neutrophilic dermatosis which usually presents as an idiopathic disorder. The combination of Sweet's syndrome and sarcoidosis is rare. We report the clinical case of a Sweet's syndrome revealing sarcoidosis. PMID- 27279950 TI - [Postoperative necrotizing fasciitis: a rare and fatal complication]. AB - Postoperative parietal complications can be exceptionally severe and serious threatening vital prognosis. Necrotizing fasciitis is a rare infection of the skin and deep subcutaneous tissues, spreading along fascia and adipose tissue. It is mainly caused by group A streptococcus (streptococcus pyogenes) but also by other bacteria such as Vibrio vulnificus, Clostridium perfringens or Bacteroides fragilis. Necrotizing fasciitis is a real surgical and medical emergency. We report, in this study, a very rare case of abdominal parietal gangrene occurring in a 75-year-old woman on the fifth day after surgery for an ovarian cyst. Evolution was marked by occurrence of a refractory septic shock with a rapidly fatal course on the third day of management. PMID- 27279951 TI - [Post-traumatic rupture of a liver hydatid cyst into the peritoneal cavity]. PMID- 27279952 TI - Perceptions and uptake of health insurance for maternal care in rural Kenya: a cross sectional study. AB - INTRODUCTION: In Kenya, maternal and child health accounts for a large proportion of the expenditures made towards healthcare. It is estimated that one in every five Kenyans has some form of health insurance. Availability of health insurance may protect families from catastrophic spending on health. The study intended to determine the factors affecting the uptake of health insurance among pregnant women in a rural Kenyan district. METHODS: This was cross-sectional study that sampled 139 pregnant women attending the antenatal clinic at a level 5 hospital in a Kenyan district. The information was collected through a pretested interview schedule. RESULTS: The median age of the study participants was 28 years. Out of the 139 respondents, 86(62%) planned to pay for their deliveries through insurance. There was a significant relationship between insurance uptake and marital status Adjusted odds ratio (AOR) 6.4(1.4-28.8). Those with tertiary education were more likely to take up insurance AOR 5.1 (1.3-19.2). Knowing the benefits of insurance and the limits the insurance would settle in claims was associated with an increase in the uptake of insurance AOR 7.6(2.3-25.1), AOR 6.4(1.5-28.3) respectively. Monthly income and number of children did not affect insurance uptake. RESULTS: Being married, tertiary education and having some knowledge on how insurance premiums are paid are associated with uptake of medical insurance. Information generated from this study if utilized will bring a better understanding as to why insurance coverage may be low and may provide a basis for policy changes among the insurance companies to increase the uptake. PMID- 27279953 TI - [Multidrug-resistant tuberculosis in children: about two cases]. AB - Multidrug-resistant tuberculosis in children is a severe form of tuberculosis, which remains a major health problem especially in developing countries. We report the case of two children treated, during our training, for multidrug resistant tuberculosis and put on second-line regimen. PMID- 27279954 TI - [Knee chondromatosis complicated by secondary genu valgum with common peroneal nerve compression]. PMID- 27279955 TI - The prevalence of hepatitis B virus infection in Nigerian children prior to vaccine introduction into the National Programme on Immunization schedule. AB - INTRODUCTION: Hepatitis B virus infection is a major global health problem of public health importance. In a bid to control the infection, the Nigerian government in 2004 introduced hepatitis B vaccine into the National Program on Immunization. There are no studies on the prevalence of hepatitis B in adolescent prior to 2004. The study was aimed at determining the seroprevalence and predictors of viral Hepatitis B in Nigerian children aged 11-19 years. METHODS: A cross sectional analytical study was conducted in July 2014. Multi-staged sampling technique was used to select 749 children from six secondary schools in Calabar, Cross River State, Nigeria. Ethical clearance was obtained from the Cross River State Medical Ethical Committee. A validated structured interviewer administered questionnaire was used to obtain information from participants following parental consent. Blood samples were obtained for qualitative detection of HBsAg using rapid chromatographic immunoassays with test kits from ABON (China) having sensitivity, specificity and accuracy of >99%, 97% and 98.5% respectively. Data was analyzed using SPSS version 20.2. RESULTS: Nine of the749 students screened were positive for HBsAg giving an overall prevalence of 1.2%. The sex specific prevalence was 0.8% for males and 1.8% for females. After multivariate analysis, age was the predictor of hepatitis B infection (OR 3.92; 95% CI 1.22-12.63; p-value 0.02). CONCLUSION: The prevalence of HBV infection was low. Despite the low prevalence, the introduction of the vaccine is justifiable in view of the public health importance of the infection. PMID- 27279956 TI - [Iodine concentration in cooking salt consumed in Lubumbashi and the iodine status of vulnerable people: case study of pregnant women living in underprivileged areas]. AB - INTRODUCTION: Consumption of low iodine salt can cause different types of disorders associated with iodine deficiency. This study aims to determine iodine content in table salt consumed in Lubumbashi and iodine status of pregnant women who are the main target of iodine deficiency. METHODS: aAdescriptive cross sectional study was devoted to an iodometric iodine analysis of 739 salt samples collected from the households and the markets of Lubumbashi in 2014. Previously, urinary iodine concentrations were determined in 225 pregnant women received for consultation from 15 March 2009 to 25 April 2011 by mineralization technique using ammonium persulphate. RESULTS: Our survey found that 47.5% of the cooking salt samples were adequately iodized (from 15 to 40 ppm), 36,9% of the samples had low iodine levels, 7,4% of the samples had too much iodine and 8,1% of the samples were not iodized. Iodine concentration in the analyzed cooking salt reached an overall average of 54,9%, being clearly below the WHO Standards (90%). By measuring urinary iodine concentration of pregnant women, iodine deficiency (urinary iodine <150 ug/l) was observed in 52%. CONCLUSION: The low availability of iodine from consumed salt in Lubumbashi could be responsible for a large proportion of the observed iodine deficiency in pregnant women, exposing them to the major risks for disorders associated with iodine deficiency. PMID- 27279957 TI - [Small cell bronchial carcinoma and pregnancy: about a case with review of the literature]. AB - Bronchopulmonary cancer (CBP) in pregnant woman is a rare entity with a poor outcome. This situation is becoming increasingly common, due to the increase in smoking among women. Transplacental transmission of tumor associated with fetal damage is described especially among untreated women. Treatment is multidisciplinary and it is not well codified. We report the case of a 23 year old patient with small cell bronchial carcinoma diagnosed during pregnancy. She had received chemotherapy during pregnancy and it was well tolerated. Radiological evaluation objectified a stabilization of the pulmonary process. The treatment was completed with concomitant radiochemotherapy after delivery. PMID- 27279958 TI - [Postcoital bleeding: 68 case-reports and review of the literature]. AB - Consensual or imposed sexual act can cause traumas. Post coital bleeding is a common gynecological symptom. It can reveal serious problems. The aim of our study is to analyze the epidemiological, diagnostic and therapeutic profile as well as preventive measures in case of post coital tear. This is a prospective study, over two years, conducted in the Department of Obstetrics and Gynecology at the Center Hospital University Mohammad VI (CHU) in Marrakech. We collected 68 patients. The average age was 27 years. Most of the patients were nulliparous (89.7% of the cases). Half of the patients had traditional wedding. Sexual intercourse was consensual in 74% of the cases. Vaginal bleeding was the most frequent reason for consultation (98% of the cases). Hymenal lesions were found in 39% of the cases and the lesion involved the posterior fornix of the vagina in 35% of the cases. Therapeutic management consisted of a surgical suture in 97% of the cases, associated with blood transfusion in two patients and sexual abstinence of all patients for at least two weeks. The social context as well as the lack of sex education were often highlighted, hence the importance of psychological support to prevent both the impact of traumas on sexuality and the recurrences. PMID- 27279959 TI - Avulsion of the tuberosity of the calcaneus, an unusual injurie: case report. PMID- 27279960 TI - [A rare mode of revelation of Wegener's granulomatosis: myocarditis associated with a fibroblastic endocarditis]. AB - We report, through this observation, a rare case of Wegener's disease revealed by myocarditis associated with fibroblastic endocarditis. The patient was initially admitted to hospital with global heart failure. The ECG showed atrial flutter rhythm disorder. Echocardiographic examination revealed non-dilated left ventricle with severe dysfunction and positive troponin dosage. Severe renal failure was discovered fortuitously and required hemodialysis. It was associated with an inflammatory anaemia confirmed by serum ferritin and myelogram. c-ANCA dosage was strongly positive, confirming the diagnosis. Chest CT scanning objectified right basal pneumonia. After starting appropriate treatment, including corticotherapy and immunosuppressive treatment, evolution was favorable with the normalization of left ventricular systolic function. Although obvious clinical cardiac events are rare, cardiac involvement in Wegener's disease is described, requiring rapid diagnostic orientation and rigorous knowledge of this serious disease. PMID- 27279961 TI - Trend in mortality from a recent measles outbreak in Cameroon: a retrospective analysis of 223 measles cases in the Benakuma Health District. AB - INTRODUCTION: Measles is a highly contagious viral infection with high mortality in poorly vaccinated regions. We sought to establish the trend in mortality and the factors that favoured the recent measles outbreak that occurred in Benakuma, in the North west region of Cameroon from the 21/06/2015 to 26/09/2015. METHODS: We carried out a retrospective register analysis of 223 measles cases. Time trends were established using the Mann-Kendall test while survival was assessed using the Kaplan-Meier survival analysis and log rank test for comparisons. RESULTS: We had a case fatality of 8.5% and the mortality decreased significantly (p = 0.01) after the following public health interventions were instituted: community sensitisation and education; outbreak response immunisation and the use of a clinician in controlling the outbreak. Furthermore, the number of cases (p < 0.01) and the duration from onset of illness to consultation at a health facility (p < 0.01) decreased significantly after the institution of the aforementioned interventions. Also, survival during the outbreak was better in females (p = 0.02) and in those treated in health facilities (p < 0.01). CONCLUSION: The poor vaccination status in Benakuma coupled with negative cultural beliefs; poor socioeconomic and environmental factors and inadequate public health policies predisposed the region to a measles outbreak and favoured the spread of the virus. Public health policies should be revisited, modified and intensified to scale up vaccination coverage in measles endemic zones in Cameroon to help eliminate the disease and facilitate the overall attainment of the Sustainable Development Goals. PMID- 27279962 TI - [Factors associated with cephalic load carriage in children in Benin: cross sectional study]. PMID- 27279963 TI - [Trans-scapholunate dislocation associated with a vertical fracture-dislocation of the pyramid: a very rare case]. PMID- 27279964 TI - [Infectious profile and mortality of children aged 0-5 years admitted with severe acute malnutrition: a retrospective cohort study conducted in the Therapeutic Nutritional Center in Bukavu, Republic of Congo]. AB - INTRODUCTION: Malnutrition is a backdrop on which several infections are grafted. The aim of this study is to determine the most lethal infections, the median length of stay and the median daily weight gain of malnourished children. METHOD: A retrospective cohort study of malnutrition in children aged 0-59 months hospitalized in the Therapeutic Nutritional Center in Bukavu from 1 January 2011 to 31 December 2013. The evaluation of the risk of deaths related to infectious complication was made measuring the relative risk. Mann-Whitney test was used for comparing the medians. Adjusted odd ratios using logistic regression and 95% confidence interval for the risk of mortality were given for each infectious cause. RESULTS: A total of 574 children were included in the study. Five hundred twenty-one (90.8%) children were cured, 10 (1.7%) had discontinued treatment and 43 (7.5%) had died. The median length of stay was 19 (13-26) days and the median daily weight gain was 7 (3-13) g/kg/j. There was a statistically significant association between mortality and sepsis/septic shock (p = 0.0004), meningitis (p = 0.00001) and HIV infection (p = 0.02). CONCLUSION: A better management of acute malnutrition in our region should be based on the establishment of specialized and well equipped units for the treatment of malnutrition associated with severe infections. PMID- 27279965 TI - Trend of invasive pneumococal disease (IPD) in a South Western, Nigerian hospital. AB - The recent introduction of the Heptavalent-pneumococcal vaccine (PCV-7) by private pharmaceutical companies in Nigeria, has generated interest in invasive bacterial diseases particularly IPD. Our objective in this study is to investigate the trend and occurrence rate of IPD in Abeokuta, Nigeria. Suspected IPD cases were assessed from Jan 2010 to Dec 2010 for demographic and Microbiological characteristics. Bacterial isolations and antibiotics susceptibility testing followed standard bacteriological procedure. Overall 471 cases of probable IPD was assessed, with 21(4.5%) cases of suspected pneumonia, 109(23.1%) cases of suspected meningitis, and 341(72.4%) cases of suspected septicaemia. Confirmed IPD cases were 9 with 2 cases of meningitis, 3 cases of septicaemia and 4 cases of pneumonia. Age range distribution showed, high distribution of IPD cases among children >1 with 5(55.6%) there was a statistically significant difference in gender p< 0.05 (X2 test) with females recording a higher occurrence than males. We conclude by advocating for better detection methods against IPD meningitis cases, and continuous surveillance into the serotypes of streptococcus pneumonia as well inclusion of the PCV vaccine into our childhood immunization program. PMID- 27279966 TI - [A retrospective study on the incidence of chronic renal failure in the Department of Internal Medicine and Nephrology at University Hospital of Antananarivo (the capital city of Madagascar)]. AB - Chronic renal failure is a global public health problem. In developed countries, this disease occurs mainly in the elderly, but in Africa it rather affects active young subjects. This disease need for expensive treatments in a low income country, because of its costs. Our aim is to describe the epidemiology of new cases of chronic renal failure in Madagascar. This is a retrospective, descriptive study of 239 patients with chronic renal failure over a 3 year period, starting from 1 January 2007 to 31 December 2009, in the Department of Internal Medicine and Nephrology at University Hospital of Antananarivo. The incidence was 8.51% among patients hospitalized in the Department. The average age of patients was 45.4 years with extremes of 16 and 82 years and a sex ratio 1,46. The main antecedent was arterial hypertension (59.8%). Chronic renal failure was terminal in 75.31% of the cases (n=180). The causes of chronic renal failure were dominated by chronic glomerulonephritis (40.1%), nephroangiosclerosis (35.5%). Hemodialysis was performed in 3 patients (1.26%), no patient was scheduled for a renal transplantation. Mortality rate in the Department was 28.87%. Chronic renal failure is a debilitating disease with a dreadful prognosis which affects young patients in Madagascar. Its treatment remains inaccessible to the majority of patients. The focus must be mainly on prevention, especially on early effective management of infections, arterial hypertension and diabetes to reduce its negative impacts on the community and public health. The project on renal transplantation: living donor, effective and less expensive treatment compared to hemodialysis could also be a good solution for these Malagasy young subjects. PMID- 27279967 TI - [Synchronous bilateral breast cancer and pregnancy: about 3 cases at Joliot Curie institute of Dakar (Senegal)]. AB - To describe our diagnostic and therapeutic strategy against synchronous, bilateral breast cancer during the pregnancy. Gestational age at diagnosis of cancer was 7; 21 and 25 weeks respectively. Patients had stage IV and IIIA of breast cancer in two and one case respectively. They all received chemotherapy, two cases during pregnancy (6TEC and 3AC) and one case after delivery. Bilateral mastectomy was performed in one case. One patient died. The others were alive but all metastatic. Fetal growth restriction was noted in one case. This association leads to delayed diagnosis of cancer. Surgery is feasible and the type of intervention is only determined by the cancer stage. Chemotherapy is feasible and is associated with less foetal complications in the last two quarters of pregnancy. PMID- 27279968 TI - An unusual etiology of posttraumatic Collet-Sicard Syndrome: a case report. AB - Posttraumatic Unilateral paralysis of the last four cranial nerves (IX-XI), known as collet-Sicard syndrome, is rare following closed head injury. A 21-year-old man presented with slurred speech, hoarseness voice and difficulty swallowing his saliva following closed head trauma. The cranial nerve examination revealed left sided severe dysfunction of cranial nerves VII, IX, X, XI, and XII. A CT-Scan of the neck was performed demonstrating a fracture of the left styloid process at the base of the skull. The Magnetic Resonance Imaging showed unusually well seen lower cranial nerves due to nerve edema. The patient was managed conservatively with steroids and regular sessions of neuromuscular and orthophonic rehabilitation. The nutrition had to be administered by gastrostomy since he was unable to swallow. Six months after the injury a total neurological recovery was noted. We present the exceptional case of Collet-Sicard Syndrome caused by styloid process fracture. PMID- 27279969 TI - [Radiotherapy for endometrial cancer: experience of the national institute of oncology with 52 cases]. AB - Endometrial cancer is the most common gynecological cancer in the Western world. It affects mainly postmenopausal women. The aim of our study is to report the experience of the radiotherapy department of the National Oncology Institute (INO) in the treatment of endometrial cancer. We retrospectively analyzed 52 cases of endometrial cancer treated in the INO radiotherapy department between 2007-2009. Data obtained from the patient medical records were related to the epidemiologic, clinical, therapeutic and evolutionary aspects of this cancer. The median age of the patients was 57 years, 87% were postmenopausal. The median of consultation time was six months. The main symptom was metrorrhagia (51 patients). Histological diagnosis was based on biopsic curettage of uterine endometrium in 51% of the cases. Anatomo-pathological examination showed an endometrioid adenocarcinoma in 92% of the cases. After the assessment, 27% of the patients were stage I, 30% stage II, 20% stage III and 1% stage IVA, according to the International Federation of Gynecological and Obstetrics (FIGO) stage classification. After surgery, 51% of the patients received postoperative external radiotherapy. The delivered dose was 46 Gray (Gy). All patients received internal vaginal brachytherapy. From an evolutionary perspective, 83% of the patients had no recurrences during the follow-up period, 8% of patients had a local recurrence and 4% of patients had distant metastases. Therefore, surgery is the main treatment for endometrial cancer. Radiotherapy is the primary adjuvant treatment. PMID- 27279970 TI - Evaluation of water, sanitation and hygiene program outcomes shows knowledge behavior gaps in Coast Province, Kenya. AB - INTRODUCTION: Water related diseases constitute a significant proportion of the burden of disease in Kenya. Water, sanitation and hygiene (WASH) programs are in operation nation-wide to address these challenges. This study evaluated the impact of the Sombeza Water and Sanitation Improvement Program (SWASIP) in Coast Province, Kenya. METHODS: This study is a cluster randomized, follow-up evaluation that compared baseline (2007) to follow-up (2013) indicators from 250 households. Twenty-five villages were selected with probability proportional to size sampling, and ten households were selected randomly from each village. Follow-up data were collected by in-person interviews using pre-tested questionnaires, and analyzed to compare indicators collected at baseline. Cross sectional results from the follow-up data were also reported. RESULTS: Statistically significant improvements from baseline were observed in the proportions of respondents with latrine access at home, who washed their hands after defecation, who treated their household drinking water and the average time to collect water in the dry season. However, this study also observed significant decreases in the proportion of respondents who washed their hands before preparing their food, or feeding their children, and after attending to a child who has defecated. The analysis also revealed a knowledge-behavior gap in WASH behaviors. CONCLUSION: SWASIP contributed to improvements from baseline, but further progress still needs to be seen. The findings challenge the assumption that providing infrastructure and knowledge will result in behavior change. Further understanding of specific, non-knowledge predictors of WASH related behavior is needed. PMID- 27279971 TI - Inpatient healthcare provider bypassing by women and their children in urban Bo, Sierra Leone. AB - INTRODUCTION: Bypassing refers to a person's decision to seek care at a healthcare facility that is not the nearest one of its type to the person's home. METHODS: This study examined inpatient care facility bypassing in urban Bo, Sierra Leone using data from 1,980 women with children 15 years of age and younger who were interviewed in 2010-2011. The locations of residential structures and hospitals were identified using a geographic information system (GIS), and the road distances from participating households to the nearest and preferred inpatient care facilities were measured. RESULTS: Nine inpatient care facilities serve Bo residents, but more than 70% of the participating women reported that the city's main public hospital (Bo Government Hospital), located in the city center, was their preferred inpatient care provider. Participants resided within a median distance of 0.9 km (Interquartile range (IQR): 0.6, 1.8) from their closest inpatient facility, but they would travel a median distance of 2.4 km (IQR: 1.0, 3.3) to reach their preferred providers. About 87% of the women would bypass their nearest inpatient care facility to access care at a preferred provider. Bypassing rates were similar for various demographic and socioeconomic groups, but higher for women living farther from the city center. CONCLUSION: Although Bo has a diverse healthcare marketplace, access to affordable advanced care options is limited. Most women in Bo would choose to bypass facilities nearer to their homes to seek the low-cost and comprehensive care offered by Bo Government Hospital. PMID- 27279972 TI - Local treatment of burns by honey is not appropriate. PMID- 27279973 TI - [A rare case of suppurative mesenteric adenitis associated with intussusception in a child: a clinical case]. AB - Some cases of suppurative mesenteric adenitis have already been described in the literature but not associated with intussusception. We describe the case of a 3 year-old boy presenting to the department of surgery at the University Hospital of Lubumbashi with bowel obstruction. He was visited elsewhere, in the previous 12 days, for diarrhea, vomiting, fever, coma and treated for cerebral malaria and blackwater fever. Surgery revealed an ileal intussusception and a suppurative mesenteric adenitis whose pyoculture revealed the presence of Enterobacter cloacae, sensitive to norfloxacin. We performed desinvagination, sucked the pus out into a syringe and excized completely the site of suppurative adenitis. The evolution of patient was good. The clinician must know that the association between suppurative mesenteric adenitis and intussusceptions exists. The diagnosis is not easy and there is the risk of developing acute peritonitis due to its fistulation in the abdominal cavity. PMID- 27279974 TI - [Panniculitis in patient undergoing treatment for dermatomyositis with methotrexate]. AB - Panniculitis is a rare cutaneous manifestation of dermatomyositis (DM). The appearance of panniculitis during treatment with methotrexate (MTX) is exceptional and has only been described in 3 cases. We report a case of a 50-year old woman suffering from DM since 1997 who was treated with corticosteroids showing favorable clinical and biological evolution. When a relapse occurred 2 years later, she was treated with higher-dose of corticosteroids in combination with a 7,5 mg weekly dose of methotrexate. The evolution was rapidly favorable. Eighteen months later, the patient had multiple subcutaneous nodules on limbs and buttocks. Anatomopathological examination showed panniculitis. There was no evidence supporting progression in DM. Prednisone dose was increased to 0.5 mg/kg/day, always in combination with MTX, without any clear signs of improvement. MTX treatment was stopped and the cutaneous lesions completely disappeared in 2 months without any relapse. This objective response lasted for 42 months. Our observation is particular given the occurrence of panniculitis in a patient undergoing treatment for dermatomyositis with methotrexate and illustrates the difficulties in the diagnosis. This entity must be known despite its exceptional nature since cutting off MTX treatment generally induces the disappearance of subcutaneous nodules. PMID- 27279975 TI - [Unusual evolution of a complex bile duct injury after a laparoscopic cholecystectomy]. AB - Since the advent of laparoscopic surgery of cholelithiasis the incidence rate of bile duct injuries has increased significantly in the literature in relation to the operators' learning curve. Unknown injuries can have dramatic, immediate consequences and progress to bile peritonitis. Moreover surgical repair of external biliary fistula at the stage of bile duct dilatation requires biliodigestive anastomosis or liver resections "reglees". PMID- 27279976 TI - Nonsense-mediated mRNA decay among coagulation factor genes. AB - OBJECTIVES: Haemostasis prevents blood loss following vascular injury. It depends on the unique concert of events involving platelets and specific blood proteins, known as coagulation factors. The clotting system requires precise regulation and coordinated reactions to maintain the integrity of the vasculature. Clotting insufficiency mostly occurs due to genetically inherited coagulation factor deficiencies such as hemophilia. MATERIALS AND METHODS: A relevant literature search of PubMed was performed using the keywords coagulation factors, Nonsense mediated mRNA decay and premature translation termination codons. Search limitations included English language and human-based studies. RESULTS: Mutations that cause premature translation termination codons probably account for one third of genetically inherited diseases. Transcripts bearing aberrant termination codons are selectively identified and eliminated by an evolutionarily conserved posttranscriptional pathway known as nonsense-mediated mRNA decay (NMD). There are many pieces of evidence of decay among coagulation factor genes. However, the hemophilia gene (F8) does not seem to be subjected to NMD. Since the F8 gene is located on the X-chromosome, a connection between X-linked traits and mRNA decay could be assumed. CONCLUSION: Considering that not all genes go through decay, this review focuses on the basics of the mechanism in coagulation genes. It is interesting to determine whether this translation-coupled surveillance system represents a general rule for the genes encoding components of the same physiological cascade. PMID- 27279977 TI - Tracheal overexpression of IL-1beta, IRAK-1 and TRAF-6 mRNA in obese-asthmatic male Wistar rats. AB - OBJECTIVES: Human and animal studies have shown a close relationship between obesity and asthma severity. Here, we examined the effects of diet-induced obesity (DIO) on the expression levels of IL-1beta, IRAK-1 and TRAF-6 mRNA in male Wistar rats tracheal after sensitization with ovalbumin (OVA). MATERIALS AND METHODS: Twenty male Wistar rats divided to four groups, included, control group with normal diet (C+ND), OVA-sensitized group with normal diet (S+ND), control group with high-fat diet (C+HFD), and OVA-sensitized group with high-fat diet (S+HFD). All animals fed for 8 weeks with standard pelts or high-fat diet, and then were sensitized and challenged with OVA or saline for another 4 weeks with designed regimens. At the end of study, trachea isolated and examined for expression levels of IL-1beta, IRAK-1 and TRAF-6 mRNA with RT-PCR method. RESULTS: Diet-induced obesity groups developed increased weight, obesity indexes and lipid profiles (P<0.05 to P<0.001). The expression levels of IL-1beta mRNA in OVA-sensitization groups (S+ND and S+HFD) showed a significantly increased when compared with control group. Also in S+HFD group, expression level of TRAF-6 mRNA was higher than other groups (P<0.001). IRAK-1 expression level was high in S+HFD compared with control group.IL-1beta and TRAF-6 mRNA correlated positively with obesity indexes. CONCLUSION: The results showed that DIO causes overexpression of IL-1beta, IRAK-1 and TRAF-6 mRNA in an experimental model of asthma. Our results suggested that in obese-asthmatic conditions locally production and activation of pro-inflammatory agents can be increased. These findings showed that possible mechanism for obesity-asthma relationships. PMID- 27279978 TI - Apoptosis inducing capacity of Holothuria arenicola in CT26 colon carcinoma cells in vitro and in vivo. AB - OBJECTIVES: Sea cucumber is one of the classes of echinoderms, which is considered as a health marine product and possess various biological characteristics with therapeutic application. The present investigation attempted to evaluate the potential of anti-cancer Persian Gulf sea cucumber species Holothuria arenicola (H. arenicola) aqueous extract on mice colon carcinoma cells in vitro and in vivo. MATERIALS AND METHODS: The CT26 carcinoma cells were treated with various concentrations of extract in 24 and 48 hr, and then its anti proliferative effect was measured by MTT assay and morphological observations. The apoptotic effect was examined by fluorescence microscopy (DNA fragmentation assay), Flow cytometry, caspase-3 and -9 colorimetric assays. The in vivo anti tumor efficacy of sea cucumber extract on CT26 tumor cells transplanted in BALB/c mice was also investigated. RESULTS: The results showed that the water extract of sea cucumber revealed remarkable anti-proliferative effect on CT26 tumor cells with IC50= 31 ug/ml with recruitment of intrinsic apoptotic pathway in vitro. In addition, the colon tumor volume in treated groups remarkably reduced in homozygous mice. Histopathological examination elucidated that sea cucumber extract attenuated tumor size and volume along with apoptosis characteristics. Moreover, RT-PCR analysis revealed that sea cucumber extract induced intrinsic apoptosis in vivo through suppression of Bcl-2 expression. CONCLUSION: Our data confirmed this notion that sea cucumber administrates anti-cancer effect that can be used as complementary in preclinical experiments, so further characterization are recommended for detection sea cucumber metabolites and clinical application. PMID- 27279979 TI - Parental cigarette smoking, transforming growth factor-alpha gene variant and the risk of orofacial cleft in Iranian infants. AB - OBJECTIVES: We investigated the influence of genetic variation of the transforming growth-factor alpha (TGFA) locus on the relationship between smoking and oral clefts. MATERIALS AND METHODS: In this study 105 Iranian infants with non-syndromic cleft lip/palate and 218 controls with non-cleft birth defects were examined to test for associations among maternal exposures, genetic markers, and oral clefts. Maternal and parental smoking histories during pregnancy were obtained through questionnaire. DNA was extracted from newborn screening blood samples, and genotyping of the BamHI polymorphism in the TGFA gene was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. A number of factors including gender of the newborns, type of oral cleft, consanguinity of the parents, as well as the mother's age and education were evaluated as potential confounders and effect modifiers. RESULTS: Maternal smoking, in the absence of paternal smoking, was associated with an increased risk for CL/P (OR = 19.2, 95% CI = [(6.2-59.5)]) and cleft palate only (OR =48.7, 95% CI = [(8-29.3)]). If both parents smoked, risks were generally greater (OR = 55.6, 95% CI = [12-20.25]). Analyses for the risk of clefting from maternal smoking, stratified by the presence or absence of the TGFA/BamH1variant, revealed that the risk of clefting among the infants with the TGFA/BamH1 variant when their mothers smoked cigarettes was much greater than the infants who had non-smoker mothers (P=0.001, OR=10.4,95% CI=[3.2,33.6]). CONCLUSION: The results of this study indicate that first-trimester maternal smoking and infant TGFA locus mutations are both associated with nonsyndromic cleft lip and/or palate (CL/P). PMID- 27279980 TI - Effects of 1,25-dihydroxyvitamin D3 on IL-17/IL-23 axis, IFN-gamma and IL-4 expression in systemic lupus erythematosus induced mice model. AB - OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune disease which may be characterized by T lymphocytes dysfunctions. Th17 cells have been identified as new effector cells, which play an important role in the pathogenesis. In recent years, immunomodulatory effect of vitamin D3 has been noticed. In the present experiment, the effect of vitamin D3 on the expression of IL-17, IL-23, IL-4 and IFN-gamma were assessed in activated chromatin-induced mouse model for SLE. MATERIALS AND METHODS: Five groups of mice were included in this study; Group one received active chromatin +CFA + PBS; Group 2 received vitamin D3 starting 2 weeks before disease induction; Group 3 received vitamin D3 (50 ng/day) starting with the disease establishment; Group 4 received non active chromatin +CFA + PBS; Group 5 received CFA + PBS. On day 56 splenocytes were isolated and gene expression of interleukin IL-17, IL-23, IL-4 and IFN-gamma were analyzed by Real-Time PCR method. Proteinuria and serum anti-dsDNA and Th17 levels were measured using commercial kits. RESULTS: The results showed that IL 17, IL-23, and IFN-gamma mRNA expression, and IL-17 titers were decreased remarkably and that of IL-4 increased in mice which received vitamin D3 before SLE induction. Administration of vitamin D3 after the establishment of SLE failed to affect the IL-17 or IL-23 mRNA levels. Lastly, pre-treatment of mice with vitamin D3 decreased the anti-ds DNA antibody titer. CONCLUSION: Our findings showed that vitamin D3 supplementation in lupus induced mice through modulating the expression rate of some inflammatory cytokines diminished the inflammatory conditions in SLE. PMID- 27279981 TI - Expression of the Mir-133 and Bcl-2 could be affected by swimming training in the heart of ovariectomized rats. AB - OBJECTIVES: The beneficial and more potent role of exercise to prevent heart apoptosis in ovariectomized rats has been known. The aim of this study was to examine the effects of swimming training on cardiac expression of Bcl-2, and Mir 133 levels and glycogen changes in the myocyte. MATERIALS AND METHODS: Forty animals were separated into four groups as control, sham, ovariectomy (OVX) and ovariectomized group with 8 weeks swimming training (OVX.E). Training effects were evaluated by measuring lipid profiles, Bcl-2 and Mir-133 expression levels in the cardiac tissue. Grafts were analyzed by reverse transcription-polymerase chain reaction for Bcl-2 mRNA and Mir-133 and by Western blot for Bcl-2 protein. RESULTS: Ovariectomy down-regulated Bcl-2 and Mir-133 expression levels in the cardiac tissue, and swimming training up-regulated their expression significantly (P<0.05). CONCLUSION: Our results showed that regular exercise as a physical replacement therapy could prevent and improve the effects of estrogen deficiency in the cardia. PMID- 27279982 TI - Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model. AB - OBJECTIVES: Exposing to stress may be associated with increased production of reactive oxygen species (ROS). Therefore, high level of oxidative stress may eventually give rise to accumulation of oxidative damage and development of numerous neurodegenerative diseases. It has been presented that brain-derived neurotrophic factor (BDNF) supports neurons against various neurodegenerative conditions. Lately, there has been growing evidence that changes in the cerebral neurotrophic support and especially in the BDNF expression and its engagement with ROS might be important in various disorders and neurodegenerative diseases. Hence, we aimed to investigate protective effects of BDNF against stress-induced oxidative damage. MATERIALS AND METHODS: Five- to six-month-old male wild-type and BDNF knock-down mice were used in this study. Activities of catalase (CAT) and superoxide dismutase (SOD) enzymes, and the amount of malondialdehyde (MDA) were assessed in the cerebral homogenates of studied groups in response to acute restraint stress. RESULTS: Exposing to acute physiological stress led to significant elevation in the markers of oxidative stress in the cerebral cortexes of experimental groups. CONCLUSION: As BDNF-deficient mice were observed to be more susceptible to stress-induced oxidative damage, it can be suggested that there is a direct interplay between oxidative stress indicators and BDNF levels in the brain. PMID- 27279983 TI - The effect of spinally administered WIN 55,212-2, a cannabinoid agonist, on thermal pain sensitivity in diabetic rats. AB - OBJECTIVES: Diabetic neuropathy (DN) is a common complication of diabetes that leads to allodynia, impaired nerve conduction, and progressive sensory loss. The aim of this study was to observe the effect of a high-affinity cannabinoid receptors agonist, WIN 55,212-2, on thermal hyperalgesia, nerve conduction velocity and sciatic nerve histopathology in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in rats using a single dose of streptozotocin (45 mg/kg IP). RESULTS: Intrathecal (IT) administration of WIN55, 212-2 (1, 10, 100 ug/10 ul, IT), produced antinociceptive effects in the hot plate test and also improved nerve conduction velocity (100 ug/10 ul, IT) and sciatic nerve histology. CONCLUSION: These data show that cannabinoids have potent antinociceptive effects through direct actions in the spinal dorsal horn of nociceptive pathway. This suggests that intrathecally administered cannabinoids may offer hopeful strategies for the treatment of diabetic neuropathic pain. PMID- 27279984 TI - Effect of carvacrol on various cytokines genes expression in splenocytes of asthmatic mice. AB - OBJECTIVES: With regard to pharmacological effects of carvacrol on the respiratory system, its effect on cytokines genes expression in splenocytes of asthmatic mice was examined in this study. MATERIALS AND METHODS: Splenocytes were isolated from non-sensitized (control group), sensitized mice to ovalbumin (OVA) (group S), and S animals treated with dexamethasone, and three concentrations of carvacrol. IL-4, IFN-gamma, TGF-beta, FOXP3, and IL-17 genes expression were carried out in cultured splenocytes using the real-time PCR method. RESULTS: Compared to the control group, IFN-gamma and FOXP3 genes expression were significantly decreased (P<0.001 for both cases), but IL-4 and IL 17 genes expression were significantly increased in the S group (P<0.001 and P<0.05, respectively). IL-4 gene expression due to treatment of all concentrations of carvacrol, TGF-beta gene expression due to its two higher concentrations, and IL-17 gene expression due to its high concentration were significantly decreased compared to group S (P<0.01 to P<0.001). IFN-gamma gene expression was significantly increased due to last carvacrol concentration (300 ug/ml, P<0.01), and FOXP3 due to its two last concentrations (150 and 300 ug/ml, P<0.05 and P<0.001, respectively) in treated S splenocytes. Dexamethasone treatment of sensitized splenocytes only showed significant inhibitory effect on IL-4 and TGF-beta genes expression (P<0.001 for both cases). CONCLUSION: These results showed the immunomodulatory effect of carvacrol indicating increased IFN gamma and FOXP3 but decreased IL-4, TGF-beta, and IL-17 genes expression, which was more selective than the effect of dexamethasone in sensitized mice splenocytes, which indicates its possible therapeutic value in allergy, autoimmunity, and infectious diseases. PMID- 27279985 TI - Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway. AB - OBJECTIVES: We previously reported a series of quinazoline derivatives as vascular-targeting anticancer agents. In this study, we investigated the mechanism underlying the anti-angiogenic activity of the quinazoline derivative compound 11d. MATERIALS AND METHODS: We examined the effects of quinazoline derivative 11d: on vascular endothelial growth factor receptor-2 (VEGFR2) activation via VEGFR2-specific activation assay. Reverse transcription and immunohistochemistry were used to detect vascular endothelial growth factor (VEGF), VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway in human umbilical vascular endothelial cells and hepatocellular carcinoma cells (HepG-2) after treatment with various concentrations of 11d: (0, 6.25, 12.5, and 25 MUM) for 24 hr. RESULTS: The compound 11d: exhibited potent inhibitory activity against VEGFR2 with an IC50 of 5.49 MUM. This compound significantly downregulated VEGF, VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway in vitro. CONCLUSION: The mechanism underlying the anti-angiogenic activity of the quinazoline derivative 11d: possibly involves the inhibition of VEGFR2 and the downregulation of VEGF, VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway. Overall, the findings indicate that the studied class of compounds is a source of potential antiproliferative and anti angiogenic agents, which must be further investigated. PMID- 27279986 TI - Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats. AB - OBJECTIVES: Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ) induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD). In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. MATERIALS AND METHODS: Diabetic rats were treated with naringin (100 mg/kg/d) for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)] and inflammatory cytokines (TNF-a, IL-1beta, and IL-6) were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARgamma were evaluated by real time (RT)-PCR and Western blot analysis. RESULTS: The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-alpha, IL-1beta, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARgamma expression. CONCLUSION: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD. PMID- 27279987 TI - Inhibitory effect of clemastine on P-glycoprotein expression and function: an in vitro and in situ study. AB - OBJECTIVES: Transporters have an important role in pharmacokinetics of drugs. Inhibition or induction of drug transporters activity can affect drug absorption, safety, and efficacy. P-glycoprotein (P-gp) is the most important membrane transporter that is responsible for active efflux of drugs. It is important to understand which drugs are substrates, inhibitors, or inducers of P-gp to minimize or avoid unwanted interactions. The aim of this study was to investigate the effects of clemastine on the expression and function of P-gp. MATERIALS AND METHODS: The effect of clemastine on P-gp function and expression was evaluated in vitro byrhodamine-123 (Rho123) efflux assay in Caco-2 cells and Western blot analysis. Rat in situ single pass intestinal permeability model was used to investigate the clemastine effect on digoxin Peff, as a known P-gp substrate. Digoxin levels in intestinal perfusates were assayed by high performance liquid chromatography (HPLC) method. RESULTS: The Caco-2 intracellular accumulation of Rho123 in clemastine and verapamil treated cells was 90.8 +/- 9.8 and 420.6+/ 25.4 pg/mg protein, respectively which was significantly higher than that in control cells (50.2+/-6.0; P<0.05). Immunoblotting results indicated that clemastine decreased expression of P-gp in Caco-2 cells in vitro. More over effective intestinal permeability (Peff) of digoxin in the presence of clemastine, was significantly increased compare to control group. CONCLUSION: Findings of our study suggested dose dependent P-gp inhibition activity for clemastine in vitro and in situ. Therefore co-administration of clemastine with P gp substrates may result in unwanted interactions and side effects. PMID- 27279988 TI - Evaluation of antioxidant and cytoprotective activities of Artemisia ciniformis extracts on PC12 cells. AB - OBJECTIVES: In the current study antioxidant capacities of five different extracts of Artemisia ciniformis aerial parts were evaluated by cell-free methods. Then seven fractions of the potent extract were selected and their antioxidant capacity was assayed by cell free and cell based methods. MATERIALS AND METHODS: Antioxidant ability was measured using the: 2, 2-diphenyl-1 picrylhydrazyl (DPPH) radical scavenging test, beta-carotene bleaching (BCB) method and ferrous ion chelating (FIC) assay. Total phenolic contents (TPC) of all the samples also were determined. The cytoprotective effect of fractions was evaluated by measuring the viability of cells after exposure to doxorubicin (DOX). The mechanism of action was studied by investigating caspase-3, mitochondrial membrane potential (MMP), the level of super-oxide dismutase (SOD) and intracellular reactive oxygen species (ROS). RESULTS: Hydroethanolic extract exhibited a notably higher antioxidant activity and phenolic content. Among the fractions (A to G) of hydroethanolic extract, the highest antioxidant capacity was observed in the Fraction E. Moreover, 24 hr pretreatment of PC12 cells with fractions B, C and D decreased DOX-induced cytotoxicity. In addition, pre treatment of cells with fraction B resulted in significant decrease in generation of the reactive oxygen species (ROS) and increase in the activity of SOD. We were able to demonstrate remarkable reduction in the activity of caspase-3 and increase in MMP in PC12 cells following pretreatment with fraction B. CONCLUSION: Our observations indicated that the fraction B of A. ciniformis hydroetanolic extract possessed protective effect on oxidative stress and apoptosis induced by DOX in PC12 cells. PMID- 27279989 TI - Brain-derived neurotrophic and immunologic factors: beneficial effects of riboflavin on motor disability in murine model of multiple sclerosis. AB - OBJECTIVES: In the present study, C57BL/6 female mice (n=56) were used to explore the neuroprotective effects of riboflavin in motor disability of experimental autoimmune encephalomyelitis (EAE) as a model of multiple sclerosis. MATERIALS AND METHODS: The animals were assigned into 7 groups: sham-operated 1 (SO1), healthy mice receiving PBS (phosphate buffer saline); sham-operated 2 (SO2), healthy mice receiving PBS and riboflavin; sham treatment 1 (ST1), EAE mice receiving water; sham treatment 2 (ST2), EAE mice receiving sodium acetate buffer; treatment 1 (T1), EAE mice receiving interferon beta-1a (INFbeta-1a); treatment 2 (T2), EAE mice receiving riboflavin; treatment 3 (T3), EAE mice receiving INFbeta-1a and riboflavin. After EAE induction, scoring was performed based on clinical signs. Upon detecting score 0.5, riboflavin at 10 mg/kg of body weight and/or INFbeta-1a at 150 IU/g of body weight administration was started for two weeks. The brain and spinal cord levels of brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and interleukin-17A (IL-17A) were studied using real-time PCR and ELISA methods. RESULTS: BDNF expression and protein levels were increased in the brain and spinal cord of the T3 group compared with the other groups (P<0.01). IL-6 and IL-17A expressions were increased in the brains of the T3 and T1 groups, respectively, compared to the other groups (P<0.01). The daily clinical score was reduced significantly by riboflavin in both effector and chronic phases of the disease compared with that of the controls (P<0.05). CONCLUSION: Our findings showed that riboflavin is capable of suppressing the neurological disability mediated by BDNF and IL-6. PMID- 27279990 TI - Design of cocktail peptide vaccine against Cytomegalovirus infection. AB - OBJECTIVES: Human Cytomegalovirus (HCMV) remains a major morbidity and mortality cause in immuno suppressed patients. Therefore, significant effort has been made towards the development of a vaccine. In this study, the expression of the pp65 and gB fusion peptides and Fc domain of mouse IgG2a as a novel delivery system for selective uptake of antigens by antigen-presenting cells (APCs) in Pichia pastoris yeast system were studied. MATERIALS AND METHOD: In this study, four immune dominant sequences in pp65 protein and 3 immuno dominant sequences in gB protein were selected according to literature review. Peptide linker -GGGGS- was used for construction of fusion peptide. This fusion peptide was cloned in the pPICZalphaA expression vector and transfected into P. pastoris host cells. RESULTS: Dot blot and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) techniques showed that a high level of pp65-gB-Fc fusion peptide was expressed. CONCLUSION: This CMV pp65-gB-Fc fusion peptide could be a promising candidate for the development of a novel peptide vaccine. PMID- 27279991 TI - Differences in the Biodiversity of the Fecal Microbiota of Infants With Rotaviral Diarrhea and Healthy Infants. AB - BACKGROUND: Rotaviral diarrhea (RD) has been associated with the biodiversity of the fecal microbiota in infants; however, the differences in the biodiversity of the fecal microbiota between infants with RD and healthy (H) infants have not been clearly elucidated. OBJECTIVES: This study aimed to reveal the changes in the biodiversity of the fecal microbiota of infants with RD. PATIENTS AND METHODS: For this study, 30 fecal samples from 15 RD infants and 15 H infants were collected. The biodiversity of the fecal microbiota from the two groups was compared via polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and gene sequencing. RESULTS: The Shannon-Weaver index showed that the biodiversity of the fecal microbiota from the RD infants was significantly lower (P < 0.05) than that from the H infants. All fifteen RD infants were grouped into one cluster and were separated from the H infants by the un weighted-pair group method, with the arithmetic average (UPGMA) clustering algorithm. In addition, when compared with the healthy infants, the communities of the dominant microbes, Lactobacillus and Bifidobacterium, in the fecal microbiota from the RD infants have obviously changed. CONCLUSIONS: With regard to improving the understanding of the differences in the biodiversity of the fecal microbiota between RD infants and H infants, the findings of this study can provide a possible basis to reveal the relationship between RD and intestinal microbiota. PMID- 27279992 TI - The Association of High Risk Human Papillomaviruses in Patients With Cervical Cancer: An Evidence Based Study on Patients With Squamous Cell Dysplasia or Carcinoma for Evaluation of 23 Human Papilloma Virus Genotypes. AB - BACKGROUND: Cervical cancer is one of the leading causes of cancer-related death in females. Human papilloma virus (HPV) is the major risk factor of cervical cancer. OBJECTIVES: The aim of the current study was to explore the frequency and role of 23 different HPVs in patients with cervical cancer. MATERIALS AND METHODS: Overall, 117 formalin-fix and paraffin-embedded (FFPE) tissues from cervical cancer patients with squamous cell carcinoma (SCC) or dysplasia were collected from Mirza-Kochakkhan-Jangali hospital, Tehran, Iran during year 2013, to investigate the presence of HPV- HPV- 67, 68, 6, 11, 13, 16, 17, 30, 69, 39, 40, 42, 64, 66 and 51 to 59 genotypes. RESULTS: The Pap smear report illustrated the presence of malignancy in 71 cases, while 11 cases had no evidence of malignancy. Among the patients, 26 cases had sexually transmitted disease with relative frequency of 0.58. Infection with papilloma virus was observed in 83.6% of SCC patients and 45% of the dysplasia group. The most prevalent HPV genotypes were 18 with 31.62% and 16 with 27.35% of cases. Moreover the relative frequencies of HPV-33, -6, -58, -52, -35 and -51, genotypes were 15.38, 7.69, 5.98, 5.12 and 3.41%, respectively. Among the different genotypes of HPV, 31 had the lowest and 16 had the highest relative frequency. CONCLUSIONS: Our findings demonstrate that HPV-16 and -18 have a higher prevalence in our population than 31 and 51. Further investigations are required to evaluate the role of these genotypes in a larger multicenter setting for establishing their values for early detection of patients, which is useful for screening and vaccination programs of cancerous and precancerous lesions of cervical cancer. PMID- 27279993 TI - Strategies to develop and promote public-private partnerships (PPPs) in the provision of hospital services in Iran: a qualitative study. AB - INTRODUCTION: Public-Private Partnerships (PPPs) have been constructively considered in recent years to reform health sectors in many countries. This study aimed at explaining the strategies to develop and promote PPPs in the provision of hospital services in Iran. METHODS: This qualitative study was conducted in 2015. The study population consisted of experts and professionals of the health system and individuals familiar with PPPs and roles in the development of such models in hospital services in Iran that were selected through purposeful sampling, and semi-structured interviews were used for data collection. To this end, 18 experts and professionals of the health system and individuals familiar with PPPs and roles in the development of such models in hospital services in Iran were selected. The data were analyzed and classified using MAXQDA10 software and content analysis, respectively. RESULTS: According to the results of this study, four main themes and 20 subthemes in terms of strategies to develop and promote PPPs in the provision of hospital services in Iran were identified, including changes in policies and laws, socio-cultural changes, improvement of mechanisms and current processes, and financial and capital capacity building. CONCLUSION: To develop and promote PPPs in the provision of hospital services, there is a need to consider prerequisites and measures to help such partnerships to be effective and produce valuable results. PMID- 27279994 TI - Nasopharyngeal polyp causing sensory disturbances: a case report. AB - Nasopharyngeal polyps are benign abnormal mucosal protrusions associated with nasal and pharyngeal mucosa. They are commonly found in all age groups with various symptoms. This paper presents a case of a 52-year-old male who presented with constant numbness over the dental midline and extending along the right side of the maxilla for the past few weeks. The patient also reported difficulty in breathing, especially lying down. After a comprehensive head and neck examination, including muscle palpation and temporomandibular joint examination, all within normal limits, a CNS lesion was suspected. A cranial nerve screening examination disclosed hyposensitivity in the area of teeth # 7 to 10. A panoramic radiograph demonstrated right sinus abnormality. We determined the need for additional diagnostic testing, including cone beam computed tomography, which showed a thickened sinus membrane with a polypoid structure (extending posterior from the right inferior concha into the oropharynx). The patient was referred to an ear, nose, and throat (ENT) specialist for further evaluation. The ENT diagnosis was a nasal polyp, and the patient was prescribed a steroid spray to be used three times daily. On follow-up, the patient's symptoms were reduced from constant numbness to intermittent "fading sensation" with no breathing difficulties lying down. Ancillary diagnostic testing, such as Cone Beam CT, is useful and may be required for the diagnosis of sensory disturbances in the Orofacial region. PMID- 27279995 TI - Phacoemulsification combined with deep sclerectomy augmented with mitomycin and amniotic membrane implantation in chronic primary open angle glaucoma with cataract. AB - OBJECTIVE: The aim of this study was to determine the safety and efficacy of combined phacoemulsification plus Intraocular lens (IOL) implantation with deep sclerectomy augmented with mitomycin C (MMC) and sub-flap implantation of amniotic membrane for the management of uncontrolled, chronic, primary open-angle glaucoma patients. METHODS: This prospective study included 41 patients with chronic, primary, open-angle glaucoma and cataract uncontrolled with medical treatment who underwent combined phacoemulsification augmented with mitomycin C (MMC) application and amniotic membrane implantation under the scleral flap. Intraocular pressure (IOP), visual acuity, glaucoma medications, stabilization of visual field, complications, and viability of the success rate were assessed a 36 month follow-up period. RESULTS: The mean age of cases was 54.8 +/- 5.3 years. Sixty-one percent of cases were males, and 39% were females. The mean IOP decreased from 23.8 +/- 1.8 mmHg preoperatively to 16.8 +/- 2.3 mmHg postoperatively. The overall success rate was 97.5, 95, and 92.7% in the first, second, and third year, respectively. The overall success rate was 90% in the first year, but that decreased to 85.3 and 78% in the second and third year, respectively. Qualified success was 7.5, 10, and 14.7% in the first, second, and third year, respectively. Failure was recorded as 2.5, 5, and 7.3% in the first, second, and third year, respectively. IOP reduction was sustained through the follow-up period. Visual acuity improved from 0.13 +/- 0.06 to 0.9 +/- 0.07 (p < 0.001). The visual field improved significantly in the first assessment, from 14.0 +/- 2.7 preoperatively to 12.6 +/- 2.6 at three months postoperatively (p < 0.001), after which it became stable for the remainder of the follow-up period. One hundred percent of cases were on three anti-glaucoma drugs preoperatively, while postoperatively, 12.2% were on three drugs, 4.2% were on two drugs, and 82.9% were controlled without anti-glaucoma treatment. There were minor postoperative complications all of which were minor, such as a spike in the post operative IOP and the formation of fibrinous material in the anterior chamber, both of which were treated medically without any adverse effects on the final results. CONCLUSION: Amniotic membrane implantation in conjunction with MMC application may be an effective alternative to expensive implants in deep sclerectomy combined with phacoemulsification, and this approach can be used safely in advanced cases. PMID- 27279996 TI - Clinico-laboratory profile of breath-holding spells in children in Sohag University Hospital, Upper Egypt. AB - INTRODUCTION: Breath-holding spells (BHSs) are involuntary pauses of breathing, sometimes accompanied by loss of consciousness. They usually occur in response to an upsetting or surprising situation. Breath-holding spells are usually caused by either a change in the usual breathing pattern or a slowing of the heart rate. In some children, BHSs may be related to iron deficiency anemia. The aim of the work was to study the clinical and laboratory profile of BPHs in children presented to the Neuropediatric Clinic at Sohag University Hospital. METHODS: An observational prospective study was done at Sohag University Hospital over a period of one year on children diagnosed as having BHSs by clinical history and laboratory evaluation, including complete blood count (CBC), serum iron, serum ferritin, total iron binding capacity, and Electroencephalography (EEG). RESULTS: During the period of study (one year), we reviewed data of 32 children who had been diagnosed as having BHSs. We found that cyanotic spells (71.88%) predominated over pallid spells. There were positive family histories (31.25%) and consanguinity (53.135) in the studied patients. We found a high incidence of iron deficiency anemia (62.5%) in association with BHS. Abnormal EEGs were found in (65.63%) of studied children. CONCLUSION: BHS is a common, important problem associated with iron deficiency anemia, which is, in turn, a common nutritional problem in our country. PMID- 27279997 TI - The efficacy of training of stress-coping strategies on marital satisfaction of spouses of veterans with post-traumatic stress disorder. AB - INTRODUCTION: Marital satisfaction is an important factor in people's quality of life. It has become increasingly crucial in healthcare and health research and is dependent on coping styles of people exposed to traumatic events. The aim of this study was to assess the effectiveness of coping-style training on increasing the marital satisfaction of wives of veterans with post-traumatic stress disorder (PTSD). METHODS: In this experimental study, 60 subjects were selected from the spouses of veterans with PTSD. The veterans were chosen from the Veterans Foundation of Northern Khorasan Province (Iran) in 2014. In this study, we used the Enrich questionnaire to determine the marital satisfaction of the aforementioned spouses. Subjects were assigned randomly to study and control groups. We used the training package of a Practical Guide for Stress Management according to cognitive behavioral approaches. Cognitive-behavioral group therapy was administered in 90-minute sessions over a 12-week period. We used the paired samples t-test and ANCOVA to determine the effect of Cognitive Behavior Therapy (CBT) between the two groups. RESULTS: The mean and the standard deviation of age in the study and control groups were 36.8 +/- 4.33 years and 35.3 +/- 4.7 years, respectively. According to p < 0.005, a significant difference was observed between the subjects in the two groups. Therefore, treatment with cognitive behavioral group therapy showed evidence of clinical improvements in marital satisfaction of the study group. CONCLUSION: The results of our study showed that methods of coping with stress based on CBT are effective in increasing the marital satisfaction of wives of veterans with PTSD. PMID- 27279998 TI - Subungual Ewing sarcoma/PNET tumor family of the great toe: a case report. AB - Ewing's sarcoma is seen mainly in patients less than 18. This aggressive tumor generally affects the axial skeleton and only rarely involves the acral regions. Ewing's sarcoma in the foot is inordinately scarce. Clinical features are uncertain and can imitate other common diseases. This paper presents a case of 62 year-old malewith complaints of pain and swelling of the subungual area of his right great toe. The lesion was excised, and histopathological diagnosis of Ewing's sarcoma was made. Histopathological examination, supported by immunochemical methods, remains the mainstay of diagnosis. Surgical ablation along with chemotherapy is the therapy of choice. To our knowledge, this is the first report of Ewing's sarcoma involving the nail bed of the great toe without bone erosion. The key messages of this case report is "Subungual Ewing sarcoma is a rare case, and Ewing's sarcoma must be kept in mind for acral lesions, especially in the adult population." PMID- 27279999 TI - The Effectiveness of Group Cognitive Behavioral Therapy in Treating Obsessive Compulsive Disorder in Women with Multiple Sclerosis (MS): A randomized double blind controlled trial. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is one of the most prevalent psychiatric disorders and can cause problems for individuals in all aspects of life, including social and personal dimensions. OBJECTIVE: To study the effect of group cognitive-behavioral therapy on the reduction of OCD symptoms in female participants with multiple sclerosis (MS). METHODS: This double-blind randomized control trial was conducted from May 2012 to December 2014. The participants included 75 patients with MS who suffered from OCD and were referred to the Loghman Hakim and Imam Khomeini hospitals in Tehran, Iran. Thirty participants had been diagnosed through Yale-Brown Obsessive-Compulsive Symptoms (Y-BOCS). The participants were randomly divided into an experimental group (n=15) and a control group (n=15). Eleven sessions of cognitive-behavioral therapy were provided for the experimental group. Patients in the control group continued with their normal living. Hypotheses were tested using an analysis of covariance (ANCOVA). RESULTS: A significant reduction was found in the experimental group's obsessive-compulsive symptoms after cognitive-behavioral therapy (p<0.001). In addition, mean scores for participants in the experimental group were significantly lower than for those in the control group (p=0.000). CONCLUSION: It can be inferred that cognitive-behavioral therapy could considerably reduce OCD symptoms in women with MS. The application of this method by therapists, especially Iranian clinicians, is recommended. PMID- 27280000 TI - Determinants of job motivation among frontline employees at hospitals in Tehran. AB - INTRODUCTION: Human resources are the most strategic resource and the most significant input for health systems. Their behavior and motivation can strongly affect the overall performance of the health systems. The aim of this study was to determine the factors that affect motivation in frontline employees at teaching hospitals affiliated with Shahid Beheshti University of Medical Sciences (SBMU) in Tehran, Iran. METHODS: This cross-sectional study was conducted in 2015. The participants (nurses, physiotherapists, radiology and laboratory technicians, operating room and pharmacy staff) were 300 employees selected by the stratified random sampling method from two general and teaching hospitals. The data collection instrument was a questionnaire that consisted of 42 questions in the 7 domains of motivational factors. Data analysis was performed using descriptive statistics and independent samples t-test by SPSS software, version 23. RESULTS: The findings indicated that working relationships (mean of 3.95) were the main determinant of job motivation of frontline employees. Job content (3.76) career development (3.75), social respect (3.75), and autonomy (3.30) were the next four affective factors. Recognition and remuneration had the least influence on the job motivation of frontline employees. The results of the Friedman test indicated that the difference between the mean scores of different dimensions was significant (chi(2) (6) = 607.00, p < 0.001). CONCLUSION: A hospital that seeks to engender increased motivation of its frontline employees should have in place a human resources strategy that includes facilitating communication between personnel and management, supporting employees in the community, and promoting social respect for health professions, providing educational opportunities and career development, development of appropriate promotional policies, employee participation in goal setting, facilitating a good working environment and job security, job enrichment, and delegation. PMID- 27280001 TI - Diagnostic value of lumbar puncture among infants and children presenting with fever and convulsions. AB - INTRODUCTION: Central nervous system (CNS) infections can be categorized according to the nature of the infectious pathogen into viral, bacterial, protozoan, or fungal. The diagnosis of diffuse CNS infections depends on examination of cerebrospinal fluid (CSF) obtained by lumbar puncture (LP). The aim of this work was to determine the diagnostic value of CSF analysis in infants and children presenting with fever and convulsions. METHODS: Detailed clinical data of infants and children included in this study were collected with special reference to the course and duration of the illness, description of the convulsions, consciousness level, signs of increased intracranial pressure, and signs of meningeal irritation. Lumbar puncture and chemical and bacteriological analyses of the obtained cerebrospinal fluid were done for all of the children. RESULTS: The total number of children included in the study was 85, they had a median age 19 months, and 88% of them had generalized convulsions. CSF examination revealed that 20% had abnormal physical findings, while 23.5% had abnormal white blood cell count (WBC) (CSF Pleocytosis). CSF cultures were done in three cases with the highest White blood cells (WBCs), and streptococcus pneumoniae was present in all three cases. CONCLUSION: This study found that CNS infections are not uncommon in infants and children presenting with fever and convulsions in our locality, and acute bacterial meningitis cannot be excluded. However, its presence in the absence of clinical symptoms and signs of meningeal irritation is a remote possibility, but it should always be considered. PMID- 27280002 TI - The association between job satisfaction and general health among employees of Golestan Hospital in Ahvaz, Iran. AB - INTRODUCTION: Job satisfaction is one of the most challenging organizational concepts, and it is the basis of management policies to increase productivity and efficiency of the organization. The general health rate may affect job satisfaction in several ways. This study aimed to determine the association between job satisfaction and general health among employees of Golestan Hospital in Ahvaz, Iran. METHODS: The study population of this cross-sectional research included 100 employees of Golestan Hospital in Ahvaz, Iran. The data collection instruments were the General Health Questionnaire (28-GHQ) and the Job Descriptive Index (JDI) questionnaire. The data were analyzed using Pearson's product-moment correlation coefficient, independent samples t-test, and ANOVA statistical tests in SPSS software. RESULTS: The mean general health was calculated as 26.19 +/- 11.04, which indicated a positive psychiatric condition. Job satisfaction with a mean score of 89.67 +/- 23.3 was deemed to be relatively dissatisfied. A medium negative and significant association was observed between job satisfaction and general health and its subscales (physical health, anxiety, social, and depression). CONCLUSIONS: General health subscales and job satisfaction are associated. Some actions must be planned to cope with the negative factors in general health in order to increase employees' satisfaction in university educational hospitals. PMID- 27280003 TI - Study of the Vitamin D Levels in Patients Referred to Clinical Laboratories in Mashhad in 2015 and their Relationship with the Patients' Lipid Profiles. AB - INTRODUCTION: Vitamin D is a steroid hormone that has a significant role in the metabolism of minerals, especially calcium and phosphorus; it also is a major determinant of the strength of bones. This hormone has a significant effect on three major health issues that people worldwide encounter, i.e., high blood pressure, cancer, and diabetes. Considering the limited and dispersed studies on the prevalence of vitamin D deficiency in Iran and the relationship of vitamin D with lipid profiles in different people, this study was conducted to determine the vitamin D levels in patients and its relationship with their lipid profiles. METHODS: A retrospective cross-sectional study was conducted in 2015 on 1,110 patients who were referred to the two laboratories at Jihad Daneshgahi and to eight specialist laboratories in Mashhad through random sampling of patients for whom serum vitamin D and serum lipid tests were prescribed. The data that were obtained were entered into SPSS 13 software. RESULTS: Sixty-eight percent of the patients in the study were deficient in vitamin D. The vitamin D levels in males were significantly lower than those in females (p < 0.05). The relationship between age and vitamin D deficiency was significant as well (p < 0.05). A positive and significant relationship was observed between age and vitamin D deficiency (p = 0.000, r = 0.187), i.e., vitamin D deficiency was more apparent in patients whose ages were in the range of 40-59. The relationship between the levels of vitamin D and serum lipids was significant and positive (p = 0.05), with the exception of LDL. CONCLUSION: About two-thirds of the population that was studied had a vitamin D deficiency. There was a positive and significant relationship between serum vitamin D and serum lipids and serum calcium. The results of this study showed the necessity for more research and the implementation of preventive measures related to vitamin D deficiency. It is recommended that vitamin D enrichment programs be planned and implemented. PMID- 27280004 TI - Health-related variables and predictors of Health-promoting Lifestyle in cardiovascular disease patients. AB - INTRODUCTION: The principal cause for death in the world is cardiovascular disease. Poor lifestyle is a contributing element in this regard. The objective of this study was to estimate the effects of health-related variables and lifestyle variables on the results of exercise stress tests in patients with cardiovascular disease in Iran. METHODS: The study population in this case control study was 220 patients who were candidates for exercise stress tests in Mazandaran Province (Iran) in 2015. The patients were divided randomly into two groups based on the results of their exercise stress tests, i.e., positive (110 patients) and negative (110 patients). The data collection tool was a standard questionnaire entitled "Health promotion lifestyle profile-II." The data were analyzed using mean, standard deviation, the chi-squared test, and logistic regression by SPSS version 22 software. RESULTS: The risk of a positive exercise stress test increases with age. The age group above 65 was 1.049 times more at risk of a positive exercise stress test than the age group of less than 45. The people with dyslipidemia had 1.635 times greater risk of positive exercise stress tests than the group without dyslipidemia. In addition, patients with hypertension had 1.579 times greater risk of positive exercise stress tests than the group without hypertension. The lack of individual health responsibility (Odds ratio (OR): 1.622), stress management (OR: 1.592), and physical activity (OR: 1.245) contributed more to positive exercise tests than the other risk factors. CONCLUSION: Educational interventions can improve the responsibility for health, physical activity, and stress management among people with the risk of cardiovascular disease. PMID- 27280005 TI - A Survey of the quantity and type of biological aerosols in selected wards of a teaching hospital in Ghazvin. AB - INTRODUCTION: Bioaerosols are agents that can cause infection, allergy or induce other toxic effects in the human body. If the person exposed to such particles is not capable of their destruction or elimination from the body, the established chemical and physiological disorders can result in disease or death. The aim of this study was to assess the concentrations of bioaerosols in several wards of a teaching hospital. METHODS: Given that gas air-conditioners (split and window types) were used for ventilation in the eye operating room, internal intensive care unit, and the respiratory isolation room, these wards were selected for passive sampling. Sterile plates containing culture medium were exposed for two hours to the wards' indoor ambient air. After this time, they were transferred to a lab to undergo incubation, colony count, and identification of the microorganisms. The data were analyzed using SPSS software, version 18, and the significance level of less than 0.05 was used. RESULTS: Based on our findings, the highest colony-forming bacterial unit was observed 22 cfu/plate/h in the eye operating room and, the highest colony-forming fungal unit was observed 4 cfu/plate/h in the internal intensive care unit. Based on the results of the differential tests, the most prevalent bacteria identified were Staphylococcus epidermidis (75%) in the air of eye operating room and Staphylococcus saprophyticus (52%) in the internal intensive care unit and isolation room. The most prevalent identified fungi in the air of selected wards were related to Alternaria alternata (43%), Aspergillus flavus (24%), Penicillium (36%) and Curvularia (21%) types. Based on Spearman's correlation test, no significant relationship was observed between the factor of temperature and the number of fungal and bacterial colonies (r = 0.201, p = 0.42; r = -0.197, p = 0.41). Moreover, a meaningful relationship was observed only between the number of individuals and the bacterial colonies present in the air (r = 0.749, p = 0.0001). CONCLUSION: Comparing the number of diagnosed colonies by 25 cfu/plate/h value showed that the numbers of colonies in all samples were lower than the mentioned values. So, the air-conditioning systems' performance in reducing the number of bioaerosols in the studied wards was satisfactory. However, since the remaining bacterial and fungal contamination can cause serious infections in patients, it is highly necessary that the cleaning intervals and replacement time points of such filters be programmed based on the number of individuals present in the wards and their active surgical hours. PMID- 27280006 TI - Epidemiological aspect of scorpion sting in Bandar Abbas, Iran, during 2009-2011. AB - INTRODUCTION: People in tropical and semi-tropical areas are in danger of scorpion sting, and this can be a serious problem for them. Mortality due to scorpion sting in the tropical and semi-tropical areas of Iran is about 75%, and this makes scorpion sting in these areas a serious medical problem. Because of this problem, our aim was to assess the epidemiological aspects of scorpion sting in Bandar Abbas, Iran, during 2009-2011. METHODS: In this cross-sectional retrospective study, epidemiologic data of 698 scorpion sting cases, who were referred to the Shahid Mohamadi Hospital of Bandar Abbas in Hormozgan Province collected from 2009 until 2011. The data included demographic and individual information, such as age, gender, geographic location, bite site, when the incident occurred, and anti-venom consumption. The required data were extracted from the patients' recorded information in the Hospital, and we recorded data in a special checklist and imported the data into the computer for statistical analysis using of SPSS software, version 21.0. Descriptive statistics, including mean, standard deviation, frequency, and percentage, were used for data analysis. RESULTS: Two hundred and sixty-one (37.4%) of the cases were urban and 437(62.6%) were rural. Males comprised 50.1% of the cases, and women comprised 49.9% (p >0.05). Twenty-five point two percent of scorpion sting cases occurred among people in the 21 to 30 age group, and there were very few cases among people in the 51 to 60 age range (p<0.05). Most of cases were recorded in April and October, and the fewest cases were recorded in July and January (p<0.05); also 32.2% of scorpion sting cases occurred after midnight and in the early morning hours. CONCLUSION: Our survey showed that there was a high incidence of scorpion stings in rural areas, among 21-30 age group, among housekeepers, and among students. These results indicate the need for public education programs and better sanitation services in the rural areas around Bandar Abbas city. Prospective studies can help to health and medicine organization for prevention and treatment of scorpion sting. PMID- 27280007 TI - Molecular typing of uropathogenic E. coli strains by the ERIC-PCR method. AB - INTRODUCTION: Escherichia coli (E. coli) is the most common cause of urinary infections in hospitals. The aim of this study was to evaluate the ERIC-PCR method for molecular typing of uropathogenic E. coli strains isolated from hospitalized patients. METHODS: In a cross sectional study, 98 E. coli samples were collected from urine samples taken from patients admitted to Baqiyatallah Hospital from June 2014 to January 2015. The disk agar diffusion method was used to determine antibiotic sensitivity. DNA proliferation based on repetitive intergenic consensus was used to classify the E. coli strains. The products of proliferation were electrophoresed on 1.5% agarose gel, and their dendrograms were drawn. The data were analyzed by online Insillico software. RESULTS: The method used in this research proliferated numerous bands (4-17 bands), ranging from 100 to 3000 base pairs. The detected strains were classified into six clusters (E1-E6) with 70% similarity between them. CONCLUSION: In this study, uropathogenic E. coli strains belonged to different genotypic clusters. It was found that ERIC-PCR had good differentiation power for molecular typing of uropathogenic E. coli strains isolated from the patients in the study. PMID- 27280008 TI - Microarray-based long oligonucleotides probe designed for Brucella Spp. detection and identification of antibiotic susceptibility pattern. AB - Brucella spp. is a common zoonotic infection referred to as Brucellosis, and it is a serious public health problem around the world. There are currently six classical species (pathogenic species in both animals and humans) within the genus Brucella. The ability and practicality facilitated by a microarray experiment help us to recognize Brucella spp. and its antibiotic resistant gene. Rapid phenotypic determination of antibiotic resistance is not possible by disk diffusion methods. Thus, evaluating antibiotics pattern and Brucella detection appear necessary technique by molecular methods in brucellosis. So, the aim of this study was to design a microarray long oligonucleotides probe and primer for the complete diagnosis of Brucella spp. and obtaining genetic profiles for antibiotic resistance in bacteria at the same time. In this study, we designed 16 antibiotic-resistant gene solid-phase primers with similar melting temperatures of 60 degrees C and 16 long oligonucleotide probes. These primers and probes can identify tetracycline-, chloramphenicol-, and aminoglycoside-resistant genes, respectively. The design of microarray probes is a versatile process that be done in a wide range of selections. Since the long oligo microarray probes are the best choices for specific diagnosis and definite treatment, this group of probes was designed in the present survey. PMID- 27280009 TI - Treating anal fistula with the anal fistula plug: case series report of 12 patients. AB - INTRODUCTION: Recurrent and complex high fistulas remain a surgical challenge. This paper reports our experience with the anal fistula plug in patients with complex fistulas. METHODS: Data were collected prospectively and analyzed from consecutive patients undergoing insertion of a fistula plug from January 2011 through April 2014 at Hazrat-e-Rasoul Hospital in Tehran. We ensured that sepsis had been eradicated in all patients prior to placement of the plug. During surgery, a conical shaped collagen plug was pulled through the fistula tract. RESULTS: Twelve patients were included in this case study. All patients had previously undergone failed surgical therapy to cure their fistula and had previously-placed Setons. There were eight males and four females with an average age of 44 who were treated for complex fistulas. At a median time of follow-up of 22.7 months, 10 of the 12 patients had healed (83.3%). One patient developed an abscess that was noted on the sixth postoperative day, and there was one recurrence during follow-up. CONCLUSIONS: Fistula plugs are effective for the long-term closure of complex anal fistulas. Success of treatment with the fistula plug depends on the eradication of sepsis prior to plug placement. PMID- 27280010 TI - Validity and Reliability of Health Promoting Lifestyle Profile II in the Iranian Elderly. AB - BACKGROUND: With increasing age, the prevalence of chronic diseases increases. Since health-promoting behaviors (HPB) are considered a basic way of preventing diseases, especially chronic diseases, it is important to assess HPB. This study examines the validity and reliability of the Health Promoting Lifestyle Profile II (HPLP-II). METHODS: This is a cross-sectional study which is conducted on 502 elderly individuals aged 60 and over in Tehran, Iran. In order to determine the validity, content and construct validity were used. The content validity index (CVI) was used to assess the content validity and to assess construct validity, confirmatory factor analysis (CFA), and item-total correlations were employed. For reliability, test-retest analysis was used, and the internal consistency of the HPLP-II was confirmed by Cronbach's alpha. For data analysis, SPSS-18 and Amos-7 software was used. RESULTS: The mean age of the subjects was 66.3 +/- 5.3 years. The CVI for the revised HPLP-II and all its subscales was higher than 0.82. The CFA confirmed a six-factor model aligned with the original HPLP-II. Pearson correlation coefficients between the revised HPLP-II and their items were in range of 0.27-0.65. Cronbach's alpha of the revised HPLP-II was obtained as 0.78 and for their subscales were in the range of 0.67-0.84. Intraclass correlation coefficient was obtained 0.79 (95% confidence interval: 0.59-0.86, P < 0.001). CONCLUSIONS: The Iranian HPLP-II scale is an appropriate tool for assessing HPBs of the Iranian elderly. PMID- 27280011 TI - High Fasting Plasma Glucose Mortality Effect: A Comparative Risk Assessment in 25 64 Years Old Iranian Population. AB - BACKGROUND: High fasting plasma glucose (FPG) is one of the main leading risk factors of ischemic heart disease (IHD), stroke, and chronic kidney diseases (CKDs). We estimated population attributable fraction (PAF) and attributed death of these fatal outcomes of high FPG at national and subnational levels in 25-64 years old Iranian adult. METHODS: We used national and subnational data of the Non-Communicable Disease Surveillance Survey for exposure to risk factors in 2005 and 2011 among Iranian adults of 25-64 years old. For estimating the attributed death, using the death registration system data of Iran, we multiply the cause specific PAFs by the number of outcome-specific deaths. RESULTS: In Iran, high FPG was responsible for about 31% of attributed total deaths of IHD, stroke, and CKD in 2011. The related attributed deaths had increased from 2005 to 2011. In females, the PAFs for the effect of high FPG on IHD, stroke, and CKD were higher in 2011 than 2005 in all age groups. In males, this increase has occurred in over 45 years old. The highest PAFs of high FPG outcomes mostly related to central provinces of Iran. The central region of Iran had the highest and the southeast of the country had the lowest levels of attributed deaths. CONCLUSIONS: Considering the global 25 * 25 targets for noncommunicable disease mortality reduction, high FPG as a leading risk factor of fatal outcomes should be more targeted through the dietary, behavioral, and pharmacological interventions in Iran. PMID- 27280012 TI - Cancer Events After Acute or Chronic Exposure to Sulfur Mustard: A Review of the Literature. AB - BACKGROUND: Sulfur mustard (SM) has been considered as a carcinogen in the laboratory studies. However, its carcinogenic effects on human beings were not well discussed. The main purpose of our study is to assess carcinogenesis of SM following acute and/or chronic exposures in human beings. METHODS: The valid scientific English and Persian databases including PubMed, Web of Science, Scopus, IranMedex, and Irandoc were searched and the collected papers reviewed. The used keywords were in two languages: English and Persian. The inclusion criteria were the published original articles indexed in above-mentioned databases. Eleven full-texts out of 296 articles were found relevant and then assessed. RESULTS: Studies on the workers of the SM factories during the World Wars showed that the long-term chronic exposure to mustards can cause a variety of cancers in the organs such as oral cavity, larynx, lung, and skin. Respiratory system was the most important affected system. Acute single exposure to SM was assumed as the carcinogenic inducer in the lung and blood and for few cancers including basal cell carcinoma and squamous cell carcinoma. CONCLUSIONS: SM is a proven carcinogen in chronic situations although data are not enough to strongly conclude in acute exposure. PMID- 27280013 TI - Effects of Omega-3 Supplement in the Treatment of Patients with Bipolar I Disorder. AB - BACKGROUND: Fatty acids play various physiological roles in the organism; they are crucial for the structure of cell membranes, metabolic processes, transmission of nerve impulses and brain functions. In recent years, particular attention has been paid to the rich sources of omega-3 for the treatment of many diseases, especially mental illnesses. The present study aimed to investigate the effects of omega-3 supplement in the treatment of patients with bipolar I disorder (BID). METHODS: In this double-blind clinical trial, 100 patients suffering from BIDs were randomly divided into two, i.e. control (n = 50) and experimental (n = 50) groups. In addition to the other standard treatments, 1000 mg of omega-3 supplement was given to the experimental group on daily basis for 3 months and placebo was given to the control group. The Young Mania Rating Scale was completed for both groups before and after the intervention. Afterward, data were analyzed using paired t-test, independent t-test, and Chi-square test. RESULTS: Before intervention, mean severity of mania in the experimental group (23.50 +/- 7.02) and control group (23.70 +/- 8.09) was not significant (P <= 0.89). The difference after the intervention in the experimental group (10.64 +/- 3.3) and control group (20.12 +/- 6.78) was significant (P < 0.01). The mean intensity of mania before (23.50 +/- 7.02) and after (10.64 +/- 3.3) intervention reported to be significant at P < 0.05. CONCLUSIONS: Since omega-3 supplement was effective for the treatment of BID, it is suggested to use omega-3 supplements as an adjuvant therapy along with the other pharmacotherapies. PMID- 27280014 TI - Expanding clinical roles for nurses to realign the global health workforce with population needs: a commentary. AB - Many countries, including Israel, face health workforce challenges to meet the needs of their citizens, as chronic conditions increase. Provider shortages and geographical maldistribution are common. Increasing the contribution of nurse practitioners and other advanced practice nursing roles through task-shifting and expansion of scope-of-practice can improve access to care and result in greater workforce efficiency. Israel and many other countries are introducing reforms to expand nurses' scope-of-practice. Recent international research offers three policy lessons for how countries just beginning to implement reforms could bypass policy barriers to implementation. First, there is substantial evidence on the equivalence in quality of care, patient safety and high consumer acceptance which should move policy debates from if to how to effectively implement new roles in practice. Second, regulatory and finance policies as well as accessible advanced education are essential to facilitate realignment of roles. Third, country experience suggests that advanced practice roles for nurses improve the attractiveness of nursing as a career thus contributing to solving nursing shortages rather than exacerbating them. Designing enabling policy environments and removing barriers will gain in relevance in the future as the demand for high quality, patient-centered care is increasing. PMID- 27280015 TI - Perceptions of the quality of the therapeutic alliance in chiropractic care in The Netherlands: a cross-sectional survey. AB - BACKGROUND: Research in various medical fields demonstrates a consistent and positive association between clinical outcomes and the quality of the therapeutic alliance between the patient and clinician. The aim of this study was to explore how well chiropractors and their patients in The Netherlands perceive the quality of their working relationship. METHODS: A nationwide survey of chiropractors and their patients was conducted in The Netherlands, using a validated Dutch translation of the Working Alliance Inventory (WAV-12). Data were collected over a 5-week period in September-October 2014. Both patients and chiropractors were requested to reflect on 12 statements about to how well they perceived their collaboration in reaching consensus on treatment goals and treatment strategies, and how well they perceived the existence of an affective bond in their working relationship. A 5-point Likert scale was used to answer each question. Higher ratings reflected a more positive perception of the therapeutic alliance. Furthermore, levels of agreement between patients' and chiropractors' perceptions of the quality of their therapeutic alliance were determined. RESULTS: In total, 207 working relationships between patients and their chiropractor were analysed. The quality of the therapeutic alliance was perceived as being very positive for both patients (n = 183, mean 49.14 +/- 7.12) and chiropractors (n = 202, mean 50.48 +/- 4.97). There was no difference in patients' perceptions whether treated by a male or female chiropractor, nor in relation to the chiropractor's years of experience. Nevertheless, poor agreement was found between perceptions of patients and chiropractors in the same relationship (ICC = 0.13). CONCLUSIONS: Both patients and chiropractors perceived the quality of the therapeutic alliance as being very positive. Despite these positive results, patient and chiropractor pairs perceived the level of collaboration in order to reach agreement on treatment goals and strategies and the quality of their affective bond very differently. Clinically, these results suggest that chiropractors should, during the course of treatment, continue to collaborate with their patient and frequently verify whether their patient continues to agree with the treatment goals and treatment plan applied to further develop, improve and maintain a positive therapeutic alliance. PMID- 27280017 TI - Perioperative bridging anticoagulation for atrial fibrillation-the first randomised controlled trial. AB - ABSTRACT: Patients who have atrial fibrillation (AF) have increased thromboembolic risk. This risk is mitigated through use of anticoagulants, traditionally with vitamin K antagonists such as warfarin, and more recently with drugs such as Xa and thrombin inhibitors. Since anticoagulants increase the risk of bleeding, uncertainty exists regarding their use in the perioperative period. The risk of thromboembolism for each patient must be balanced against risk of bleeding; anticoagulation medication may be continued, replaced with a short acting alternative or withheld entirely. Until recently, evidence on best management relied on expert opinion and observational studies. The recent publication of a randomised, double-blind, placebo-controlled trial (BRIDGE) has added important information to the knowledge base. TRIAL REGISTRATION: BRIDGE ClinicalTrials.gov, NCT00786474. PMID- 27280016 TI - Dose-response of spinal manipulation for cervicogenic headache: study protocol for a randomized controlled trial. AB - BACKGROUND: Cervicogenic headache is a prevalent and costly pain condition commonly treated by chiropractors. There is evidence to support the effectiveness for spinal manipulation, but the dose of treatment required to achieve maximal relief remains unknown. The purpose of this paper is to describe the methodology for a randomized controlled trial evaluating the dose-response of spinal manipulation for chronic cervicogenic headache in an adult population. METHODS/DESIGN: This is a mixed-methods, two-site, prospective, parallel groups, observer-blind, randomized controlled trial conducted at university-affiliated research clinics in the Portland, OR and Minneapolis, MN areas. The primary outcome is patient reported headache frequency. Other outcomes include self reported headache intensity, disability, quality of life, improvement, neck pain intensity and frequency, satisfaction, medication use, outside care, cervical motion, pain pressure thresholds, health care utilization, health care costs, and lost productivity. Qualitative interviews are also conducted to evaluate patients' expectations of treatment. DISCUSSION: With growing concerns regarding the costs and side effects of commonly used conventional treatments, greater numbers of headache sufferers are seeking other approaches to care. This is the first full-scale randomized controlled trial assessing the dose-response of spinal manipulation therapy on outcomes for cervicogenic headache. The results of this study will provide important evidence for the management of cervicogenic headache in adults. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01530321). PMID- 27280018 TI - PredicT-ML: a tool for automating machine learning model building with big clinical data. AB - BACKGROUND: Predictive modeling is fundamental to transforming large clinical data sets, or "big clinical data," into actionable knowledge for various healthcare applications. Machine learning is a major predictive modeling approach, but two barriers make its use in healthcare challenging. First, a machine learning tool user must choose an algorithm and assign one or more model parameters called hyper-parameters before model training. The algorithm and hyper parameter values used typically impact model accuracy by over 40 %, but their selection requires many labor-intensive manual iterations that can be difficult even for computer scientists. Second, many clinical attributes are repeatedly recorded over time, requiring temporal aggregation before predictive modeling can be performed. Many labor-intensive manual iterations are required to identify a good pair of aggregation period and operator for each clinical attribute. Both barriers result in time and human resource bottlenecks, and preclude healthcare administrators and researchers from asking a series of what-if questions when probing opportunities to use predictive models to improve outcomes and reduce costs. METHODS: This paper describes our design of and vision for PredicT-ML (prediction tool using machine learning), a software system that aims to overcome these barriers and automate machine learning model building with big clinical data. RESULTS: The paper presents the detailed design of PredicT-ML. CONCLUSIONS: PredicT-ML will open the use of big clinical data to thousands of healthcare administrators and researchers and increase the ability to advance clinical research and improve healthcare. PMID- 27280019 TI - Low frequency of asymptomatic carriage of toxigenic Clostridium difficile in an acute care geriatric hospital: prospective cohort study in Switzerland. AB - BACKGROUND: The role of asymptomatic carriers of toxigenic Clostridium difficile (TCD) in nosocomial cross-transmission remains debatable. Moreover, its relevance in the elderly has been sparsely studied. OBJECTIVES: To assess asymptomatic TCD carriage in an acute care geriatric population. METHODS: We performed a prospective cohort study at the 296-bed geriatric hospital of the Geneva University Hospitals. We consecutively recruited all patients admitted to two 15 bed acute-care wards. Patients with C. difficile infection (CDI) or diarrhoea at admission were excluded. First bowel movement after admission and every two weeks thereafter were sampled. C. difficile toxin B gene was identified using real-time polymerase chain-reaction (BD MAX(TM)Cdiff). Asymptomatic TCD carriage was defined by the presence of the C. difficile toxin B gene without diarrhoea. RESULTS: A total of 102 patients were admitted between March and June 2015. Two patients were excluded. Among the 100 patients included in the study, 63 were hospitalized and 1 had CDI in the previous year, and 36 were exposed to systemic antibiotics within 90 days prior to admission. Overall, 199 stool samples were collected (median 2 per patient, IQR 1-3). Asymptomatic TCD carriage was identified in two patients (2 %). CONCLUSIONS: We found a low prevalence of asymptomatic TCD carriage in a geriatric population frequently exposed to antibiotics and healthcare. Our findings suggest that asymptomatic TCD carriage might contribute only marginally to nosocomial TCD cross-transmission in our and similar healthcare settings. PMID- 27280020 TI - The geographic pattern of Belgian mortality: can socio-economic characteristics explain area differences? AB - BACKGROUND: Country averages for health outcomes hide important within-country variations. This paper probes into the geographic Belgian pattern of all-cause mortality and wishes to investigate the contribution of individual and area socio economic characteristics to geographic mortality differences in men aged 45-64 during the period 2001-2011. METHODS: Data originate from a linkage between the Belgian census of 2001 and register data on mortality and emigration during the period 2001-2011. Mortality rate ratios (MRRs) are estimated for districts and sub-districts compared to the Belgian average mortality level using Poisson regression modelling. Individual socio-economic position (SEP) indicators are added to examine the impact of these characteristics on the observed geographic pattern. In order to scrutinize the contribution of area-level socio-economic characteristics, random intercepts Poisson modelling is performed with predictors at the individual and the sub-district level. Random intercepts and slopes models are fitted to explore variability of individual-level SEP effects. RESULTS: All cause MRRs for middle-aged Belgian men are higher in the geographic areas of the Walloon region and the Brussels-Capital Region (BCR) compared to those in the Flemish region. The highest MRRs are observed in the inner city of the BCR and in several Walloon cities. Their disadvantage can partially be explained by the lower individual SEP of men living in these areas. Similarly, the relatively low MRRs observed in the districts of Halle-Vilvoorde, Arlon and Virton can be related to the higher individual SEP. Among the area-level characteristics, both the percentage of men employed and the percentage of labourers in a sub-district have a protective effect on the individual MRR, regardless of individual SEP. Variability in individual-level SEP effects is limited. CONCLUSIONS: Individual SEP partly explains the observed mortality gap in Belgium for some areas. The percentage of men employed and the percentage of labourers in a sub-district have an additional effect on the individual MRR aside from that of individual SEP. However, these socio-economic factors cannot explain all of the observed differences. Other mechanisms such as public health policy, cultural habits and environmental influences contribute to the observed geographic pattern in all cause mortality among middle-aged men. PMID- 27280021 TI - Need of education for dry powder inhaler storage and retention - a patient reported survey. AB - BACKGROUND: Dry powder inhalers (DPIs) are the most commonly used devices in asthma treatment in the Nordic countries. As new DPIs become available, patients are likely to be exposed to more than one type of device, with variable optimal handling. The aim was to examine real life storage and retention of multidose DPIs in patients with asthma. METHODS: This patient-reported survey on real life storage and retention of DPIs included asthma patients using multidose DPIs. Basic patient characteristics, information on inhaler use and storage, check of expiry date, and concurrent inhaler use was examined using an on line questionnaire. RESULTS: A total of 738 patients were included with a median age of 41 years, out of which 83 % were women. Sixty-three per cent reported storage conditions pre-defined as risk locations for their maintenance inhaler and 38 % of the responding patients had more than one maintenance inhaler in use at the same time. Two thirds of the study population checked inhaler expiry date less than monthly or not at all. Use after expiry date was frequently reported. Two thirds of the patients had not received information on DPI storage, either from their doctor and/or nurse or at the pharmacy. CONCLUSIONS: This patient reported survey indicates that two thirds of the patients store their inhaler devices in suboptimal conditions, and only a minority had received instruction regarding inhaler handling. Non awareness of inhalers' expiry dates and use of more than one maintenance inhaler simultaneously was common. As inhaler mishandling may impact device functionality, improved communication and patient education is needed. PMID- 27280022 TI - Right heart in septic shock: prospective observational study. AB - BACKGROUND: The right heart often receives less attention during echocardiography. The situation is no different in septic shock. We prospectively investigated the echocardiographic indices of the right heart in septic shock adult patients. METHODS: Septic shock ICU patients within 24 h of admission were subjected to transthoracic echocardiography (TTE) as per the 2005 guidelines from the American Society of Echocardiography. RESULTS: Eighty-eight septic shock patients (M:F = 52:36) underwent TTE. Thirty-six patients survived. Significant differences in demographic and biochemical (laboratory and metabolic) parameters, severity scores, life-support therapies (vasopressors, ventilation), and length of ICU stay were observed between survivors and non-survivors. Right heart abnormalities of chamber dimension and systolic and diastolic function existed in 79, 25, and 86 % of patients, respectively. Right ventricle subcostal wall thickness (91 %), pulse Doppler myocardial performance index (73 %), and E/E' (63 %) were the predominant abnormalities in chamber dimension, systolic function, and diastolic function of the right heart, respectively. However, the presence of these abnormalities did not signify poor survival in our study. CONCLUSIONS: Right heart dimensional and functional abnormalities exist in high proportions in septic shock. However, their predictability of poor outcomes remains questionable. PMID- 27280023 TI - A systematic review of using and reporting survival analyses in acute lymphoblastic leukemia literature. AB - BACKGROUNDS: Survival analysis is commonly used to determine the treatment effect among acute lymphoblastic leukemia (ALL) patients who undergo allogeneic stem cell transplantation (allo-SCT) or other treatments. The aim of this study was to evaluate the use and reporting of survival analyses in these articles. METHODS: We performed a systematic review by searching the MEDLINE, EMBASE and Cochrane library databases from inception to April 2015. Clinical trials of patients with ALL comparing allo-SCT compared to another treatment were included. We included only studies that used survival analysis as a part of the statistical methods. RESULTS: There were 14 studies included in the review. Sample size estimation was described in 4 (29 %) studies. Only 4 (29 %) studies reported the list of covariates assessed in the Cox regression and 6 (43 %) studies provided a description of censorship. All studies reported survival curves using the Kaplan Meier method. The comparisons between groups were investigated using the log-rank test and Wilcoxon test. Crossing survival curves were observed in 11(79 %) studies. The Cox regression model was incorporated in 10 (71 %) studies. None of the studies assessed the Cox proportional hazards assumption or goodness-of-fit. CONCLUSIONS: The use and reporting of survival analysis in adult ALL patients undergoing allo-SCT have significant limitations. Notably, the finding of crossing survival curves was common and none of the studies assessed for the proportional hazards assumption. We encourage authors, reviewers and editors to improve the quality of the use and reporting of survival analysis in the hematology literature. PMID- 27280024 TI - 'Better medicines for children' within the Integrated Management of Childhood Illness framework: a qualitative inquiry in Uganda. AB - BACKGROUND: The Integrated Management of Childhood Illnesses is the main approach for treating children in more than 100 low income countries worldwide. In 2007, the World Health Assembly urged countries to integrate 'better medicines for children' into their essential medicines lists and treatment guidelines. WHO regularly provides generic algorithms for IMCI and publishes the Model Essential Medicines List with child-friendly medicines based on new evidence for member countries to adopt. However, the status of 'better medicines for children' within the Integrated Management of Childhood Illnesses approach in Uganda has not been studied. METHODS: Qualitative interviews were conducted with: two officials from the ministry of health; two district health officials and, 22 health workers from public health facilities. Interview transcripts were manually analyzed for manifest and latent content. RESULTS: Child-appropriate dosage formulations were not included in the package for the Integrated Management of Childhood Illnesses and ministry officials attributed this to resource constraints and lack of initial guidance from the World Health Organization. Underfunding reportedly undercut efforts to: orient health workers; do support supervision and update treatment guidelines to reflect 'better medicines for children'. Health workers reported difficulties in administering tablets and capsules to under-five children and that's why they preferred liquid oral dosage formulations, suppositories and injections. CONCLUSIONS: The IMCI strategy in Uganda was not revised to reflect child-appropriate dosage formulations - a missed opportunity for improving the quality of management of childhood illnesses. Funding was an obstacle to the integration of child-appropriate dosage formulations. Ministry of health should prioritize funding for the Integrated Management of Childhood Illnesses and revising the Essential Medicines and Health Supplies List of Uganda, the Uganda Clinical Guidelines and, the Treatment Charts for the Integrated Management of Childhood Illnesses to reflect child-appropriate dosage formulations. PMID- 27280025 TI - The epidemiology of patellar luxation in dogs attending primary-care veterinary practices in England. AB - BACKGROUND: Canine patellar luxation is one of the most common orthopaedic disorders of dogs and is a potential welfare concern because it can lead to lameness, osteoarthritis and pain. However, there are limited epidemiological data on the disorder relating to the general population of dogs in England. This study aimed to investigate the VetCompass Programme database of dogs attending primary-care veterinary practices in England to report on the prevalence, risk factors and clinical management of diagnosed patellar luxation cases. RESULTS: The study included all dogs with at least one electronic patient record in the VetCompass database from September 1(st), 2009 to August 31(st), 2014. Candidate patellar luxation cases were identified using free-text word searching of the clinical notes and VeNom diagnosis term fields. Univariable and multivariable binary logistic regression modelling was used for risk factor analysis. The overall dataset comprised 210,824 dogs attending 119 clinics in England. The prevalence of patellar luxation diagnosis in dogs was 1.30 % (95 % confidence interval (CI) 1.21-1.39). Of the 751 incident cases, 293 (39.0 %) received medical management, 99 (13.2 %) received surgical intervention and 28 (3.7 %) were referred for further management. Multivariable modelling documented 11 breeds with increased odds of patellar luxation compared with crossbred dogs, including the Pomeranian (odds ratio [OR]: 6.5, 95 % CI 4.0-10.7, P < 0.001), Chihuahua (OR: 5.9, 95 % CI 4.4-7.9, P < 0.001), Yorkshire Terrier (OR: 5.5, 95 % CI 4.3-7.1, P < 0.001) and French Bulldog (OR: 5.4, 95 % CI 3.1-9.3, P < 0.001). Dogs with bodyweight below their mean for breed and sex had a 1.4 times odds of diagnosis (95 % CI 1.2-1.6, P < 0.001). Dogs aged >= 12.0 years showed 0.4 times the odds (95 % CI 0.3-0.5, P < 0.001) compared with dogs aged < 3.0 years. Females had 1.3 times the odds (95 % CI 1.1-1.5, P < 0.001), neutered dogs had 2.4 times the odds (95 % CI 1.8-3.2, P < 0.001) and insured dogs had 1.9 times the odds (95 % CI 1.6-2.3, P < 0.001). CONCLUSIONS: Patellar luxation warrants inclusion as a welfare priority in dogs and control strategies that include this disorder should be considered as worthwhile breeding goals, especially in predisposed breeds. PMID- 27280026 TI - Development of a laser capture microscope-based single-cell-type proteomics tool for studying proteomes of individual cell layers of plant roots. AB - Single-cell-type proteomics provides the capability to revealing the genomic and proteomics information at cell-level resolution. However, the methodology for this type of research has not been well-developed. This paper reports developing a workflow of laser capture microdissection (LCM) followed by gel-liquid chromatography-tandem mass spectrometry (GeLC-MS/MS)-based proteomics analysis for the identification of proteomes contained in individual cell layers of tomato roots. Thin-sections (~10-MUm thick, 10 sections per root tip) were prepared for root tips of tomato germinating seedlings. Epidermal and cortical cells (5000 7000 cells per tissue type) were isolated under a LCM microscope. Proteins were isolated and then separated by SDS-polyacrylamide gel electrophoresis followed by in-gel-tryptic digestion. The MS and MS/MS spectra generated using nanoLC-MS/MS analysis of the tryptic peptides were searched against ITAG2.4 tomato protein database to identify proteins contained in each single-cell-type sample. Based on the biological functions, proteins with proven functions in root hair development were identified in epidermal cells but not in the cortical cells. Several of these proteins were found in Al-treated roots only. The results demonstrated that the cell-type-specific proteome is relevant for tissue-specific functions in tomato roots. Increasing the coverage of proteomes and reducing the inevitable cross-contamination from adjacent cell layers, in both vertical and cross directions when cells are isolated from slides prepared using intact root tips, are the major challenges using the technology in proteomics analysis of plant roots. PMID- 27280027 TI - Cerebellar involvement in Parkinson's disease resting tremor. AB - BACKGROUND: There exists a lack of consensus regarding how cerebellar over activity might influence tremor in Parkinson's disease (PD). Specifically, it is unclear whether resting or postural tremor are differentially affected by cerebellar dysfunction. It is important to note that previous studies have only evaluated the influence of inhibitory stimulation on the lateral cerebellum, and have not considered the medial cerebellum. The aim of the current study was to compare the effects of a low-frequency rTMS protocol applied to the medial versus lateral cerebellum to localize the effects of cerebellar over-activity. METHODS: Fifty PD participants were randomly assigned to receive stimulation over the medial cerebellum (n = 20), lateral cerebellum (n = 20) or sham stimulation (n = 10). 900 pulses were delivered at 1Hz at 120 % resting motor threshold of the first dorsal interosseous muscle. Tremor was assessed quantitatively (before and after stimulation) using the Kinesia Homeview system which utilizes a wireless finger accelerometer to record tremor. RESULTS: The main finding was that resting tremor severity was reduced in tremor-dominant individuals, regardless of whether stimulation was applied over the medial (p = 0.024) or lateral (p = 0.033) cerebellum, but not in the sham group. CONCLUSION: Given that the cerebellum is overactive in PD, the improvements in resting tremor following an inhibitory stimulation protocol suggest that over-activity in cerebellar nuclei may be involved in the generation of resting tremor in PD. Low-frequency rTMS over the medial or lateral cerebellum provides promise of an alternative treatment for tremor in PD, a symptom that is poorly responsive to dopaminergic replacement. PMID- 27280028 TI - Treatment provision for gambling disorder in Britain: call for an integrated addictions treatment and commissioning model. AB - Treatment provision for individuals with gambling problems in Britain is at best inadequate. Here we call for gambling treatment provision to be integrated into mainstream drug and alcohol services, and for its commissioning responsibilities to fall under local public health departments. PMID- 27280029 TI - Little evidence for community treatment orders - a battle fought with heavy weapons. AB - This editorial discusses the pros and cons of community treatment orders (CTOs) from the perspective of community general adult psychiatry. There is little scientific evidence supporting the application of CTOs. Preconditions of a CTO to work are likely to be met by few patients. The time for the application of a CTO may be better spent for patient-centred care until there is sufficient new and robust evidence that identifies the patients that might profit. PMID- 27280030 TI - Community treatment orders in the UK 5 years on: a repeat national survey of psychiatrists. AB - Aims and method Community treatment orders (CTOs) are increasingly embedded into UK practice and their use continues to rise. However, they remain highly controversial. We surveyed psychiatrists to establish their experiences and current opinions of using CTOs and to compare findings with our previous survey conducted in 2010. Results The opinions of psychiatrists in the UK have not changed since 2010 in spite of recent evidence questioning the effectiveness of CTOs. Clinical factors (the need for engagement and treatment adherence, and the achievement of adherence and improved insight) remain the most important considerations in initiating and discharging a CTO. Clinical implications Given the accumulating evidence from research and clinical practice that CTOs do not improve outcomes, it is concerning that psychiatrists' opinions have not altered in response, particularly given the implications for patient care. PMID- 27280031 TI - Community treatment orders and reduced time in hospital: a nationwide study, 2007 2012. AB - Aims and method Community treatment orders (CTOs) were introduced in Scotland in 2005, but are controversial owing to a lack of supportive randomised evidence. The non-randomised studies provide mixed results on their efficacy and utility. We aimed to examine hospital bed day usage across Scotland both before and after CTOs were initiated in a national cohort of patients, spanning 5 years. Results In total, 1558 individuals who were subject to a CTO between 2007 and 2012, of whom 63% were male, were included. After CTO initiation the number of hospital bed days fell, on average, from 66 to 39 per annum per patient. Those with a longer psychiatric history appeared to benefit more from a CTO, in terms of reduced time in hospital. Clinical implications Our data offer cautious support for the use of CTOs in routine practice, in terms of reducing time spent in psychiatric hospital. This finding is balanced by the more rigorous randomised studies which do not find any benefit to CTOs. PMID- 27280032 TI - Body mass index and blood glucose in psychiatric and general practice populations. AB - Aims and method Using a retrospective observational approach, we aimed to discern whether there was a difference in metabolic parameters between psychiatric and general practice populations in the same locality. Second, we aimed to establish differences in metabolic parameters of patients taking olanzapine, clozapine or aripiprazole. Results Patients with psychiatric illness had a body mass index (BMI) comparable to that of the general practice population (28.7 v. 29.7 kg/m(2)), but blood glucose was significantly lower in the general practice population (4.8 v. 6.1 mmol/L). Olanzapine was associated with the lowest BMI (26.1 kg/m(2)) and aripiprazole the highest (32.2 kg/m(2)), with no difference in blood glucose between antipsychotics. Clinical implications Awareness of environmental factors and how they affect individuals is important and medications are not the only cause of metabolic effects. There may be a channelling bias present, meaning practitioners are cognisant of potential metabolic effects prior to prescribing. Overall monitoring of physical health is important regardless of potential cause. PMID- 27280033 TI - Cost and carbon burden of long-acting injections: a sustainable evaluation. AB - Aims and method This study explores the economic cost and carbon footprint associated with current patterns of prescribing long-term flupentixol decanoate long-acting injections. We conducted an analysis of prescription data from a mental health trust followed by economic and carbon cost projections using local and national data. Results A reduction of L300 000 could be achieved across England by improving prescribing behaviour, which equates to L250 per patient per year and 170 000 kg CO2e. These savings are unlikely to be released as cash from the service, but will lead to higher-value service provision at the same or lower cost. Most of these carbon emissions are attributable to the carbon footprint of the appointment - 88 000 kg CO2e (including energy use and materials used) and the overprescribing of medication - 66 000 kg CO2e. Clinical implications Psychiatrists need to review their prescribing practice of long-acting injections to reduce their impact on the National Health Service financial budget and the environment. PMID- 27280034 TI - Changes in risk factors for young male suicide in Newcastle upon Tyne, 1961-2009. AB - Aims and method To ascertain differences in patterns of suicide in young men over three decades (1960s, 1990s and 2000s) and discuss implications for suicide prevention. Data on suicides and open verdicts in men aged 15-34 were obtained from coroner's records in Newcastle upon Tyne and analysed using SPSS software. Results An increase in suicide rates from the first to the second decade was followed by a fall in the third decade. This was associated with an increasing proportion of single men, those living alone, unemployment, consumption of alcohol, use of hanging, previous suicide attempt and history of treatment for mental illness. Clinical implications This study highlights the need for more interventions and focus to be given to young males in the suicide prevention area and is of high importance in the field of public health. Areas that could be tackled include reducing access to means of suicide, reducing alcohol use, support for relationship difficulties, engagement with mental health services and management of chronic illness. PMID- 27280035 TI - Mind how you cross the gap! Outcomes for young people who failed to make the transition from child to adult services: the TRACK study. AB - Aims and method The Transitions of Care from Child and Adolescent Mental Health Services to Adult Mental Health Services (TRACK) study was a multistage, multicentre study of adolescents' transitions between child and adult mental health services undertaken in England. We conducted a secondary analysis of the TRACK study data to investigate healthcare provision for young people (n = 64) with ongoing mental health needs, who were not transferred from child and adolescent mental health services (CAMHS) to adult mental health services mental health services (AMHS). Results The most common outcomes were discharge to a general practitioner (GP; n = 29) and ongoing care with CAMHS (n = 13), with little indication of use of third-sector organisations. Most of these young people had emotional/neurotic disorders (n = 31, 48.4%) and neurodevelopmental disorders (n = 15, 23.4%). Clinical implications GPs and CAMHS are left with the responsibility for the continuing care of young people for whom no adult mental health service could be identified. GPs may not be able to offer the skilled ongoing care that these young people need. Equally, the inability to move them decreases the capacity of CAMHS to respond to new referrals and may leave some young people with only minimal support. PMID- 27280036 TI - End-of-life care in a psychiatric hospital. AB - Since the Liverpool Care Pathway has been withdrawn in the UK, clinicians supporting the palliative needs of patients have faced further challenges, particularly for patients with dementia who are unable to go to a hospice owing to challenging behaviours. It is becoming more important for different services to provide long-term palliative care for patients with dementia. Mental health trusts should construct end-of-life care policies and train staff members accordingly. Through collaborative working, dying patients may be kept where they are best suited. We present the case study of a patient who received end-of-life care at a psychiatric hospital in the UK. We aim to demonstrate how effective end of-life care might be provided in a psychiatric hospital, in accordance with recent new palliative care guidelines, and highlight potential barriers. PMID- 27280037 TI - Prescribing clozapine and rifampicin: clinical impact of their interaction. AB - The predictable pharmacokinetic drug interaction between clozapine and rifampicin is listed in most standard reference texts but little detail is given or emphasis on its clinical significance. The interaction is based on theoretical knowledge of both drugs; to date just two case reports have been published. This article describes a third case demonstrating the significance of this interaction. This was potentially devastating for the patient who required an extended psychiatric admission. The enzyme induction was so potent that the dose of clozapine had to be increased approximately sixfold. Careful management of this significant interaction is essential for effective patient care. PMID- 27280038 TI - Services for people with complex psychosis: towards a new understanding. AB - This paper describes the need for commissioners and service providers to consider the development of a whole-system approach to providing rehabilitation services for patients with complex psychosis, in the context of the current economic pressures and emergence of a competitive market in this area of mental health. The practical and organisational arrangements for the management of risk with such services are described, taking into account the varying provision of rehabilitation services across the UK and considering how these can be developed against the care clustering system and interfaces with other mental health services. PMID- 27280039 TI - Protesting loudly about Prevent is popular but is it informed and sensible? PMID- 27280040 TI - Author's reply. PMID- 27280041 TI - Secure services for patients should be needs based and locally available. PMID- 27280042 TI - Predictive value of ex vivo biodynamic imaging in determining response to chemotherapy in dogs with spontaneous non-Hodgkin's lymphomas: a preliminary study. AB - Biodynamic imaging (BDI) is a novel phenotypic cancer profiling technology which optically characterizes changes in subcellular motion within living tumor tissue samples in response to ex vivo treatment with cancer chemotherapy drugs. The purpose of this preliminary study was to assess the ability of ex vivo BDI to predict in vivo clinical response to chemotherapy in ten dogs with naturally occurring non-Hodgkin's lymphomas. Pre-treatment tumor biopsy samples were obtained from all dogs and treated ex vivo with doxorubicin (10 MUM). BDI measured six dynamic biomarkers of subcellular motion from all biopsy samples at baseline and at regular intervals for 9 h following drug application. All dogs subsequently received doxorubicin to treat their lymphomas. Best overall response to and progression-free survival time following chemotherapy were recorded for all dogs. Receiver operating characteristic (ROC) curves were used to determine accuracy and identify possible cut-off values for the BDI-measured biomarkers which could accurately predict those dogs' cancers that would and would not respond to doxorubicin chemotherapy. One biomarker (designated 'MEM') showed 100% discriminative capability for predicting clinical response to doxorubicin (area under the ROC curve = 1.00, 95% CI 0.692-1.000), while other biomarkers also showed promising predictive capability. These preliminary findings suggest that ex vivo BDI can accurately predict treatment outcome following doxorubicin chemotherapy in a spontaneous animal cancer model, and is worthy of further investigation as a technology for personalized cancer medicine. PMID- 27280043 TI - Enigmatic Inv(9): A Case Report on Rare Findings in Hematological Malignancies. AB - INTRODUCTION: Inversion of chromosome 9 had been widely discussed among geneticists and evolutionary biologists because of its significant impact on various hereditary disorders and in the evolution of man. The role of such inversions in human disease evolution is an area hitherto unclear. CASE PRESENTATION: We present the case of a chronic myeloid leukemia (CML) patient who showed intermittent relapse on treatment, with a rare appearance of clones with dual inversion (9) breakpoints [inv(9)(p22q34); inv(9)(p11q21)]. We also present the first report of inv(9)(p11,q13) as the sole abnormality in a patient with chronic myeloproliferative disorder(CMPD). Both the patients registered in 2012 and were from Kerala, India. CONCLUSIONS: Both the cases discussed in our study have inv(9) as the sole abnormality and are found to confer a relatively poor prognosis. PMID- 27280045 TI - Historical Medical Value of Donguibogam. AB - Oriental medicine, since its origin in China, has had a long history extending over 2000 years. Today, it comprises several types of medicine predominately practiced in East Asia, including traditional Chinese, traditional Korean, and Kampo medicine. The distinctive medical system of traditional Korean medicine was established shortly after the publication of Donguibogam by Dr. Heo Jun in 1613. Donguibogam is highly acclaimed across East Asia; in 2009, in light of its historical medical value, the United Nations Educational, Scientific, and Cultural Organization registered the book on its cultural heritage list. Here, we review the historical medical value of Donguibogam. The findings confirm that Donguibogam developed a unique and independent form of traditional Korean medicine and innovatively reformed the disease classification system. Moreover, Donguibogam emphasized the importance of disease prevention and medical pragmatism. This book also accelerated the development of folk medicine. Owing to its historical medical value, Donguibogam is now considered the 'bible' of Oriental medicine. Its wide acceptance has contributed to the expansion of Korean medicine utilization among the general public. Donguibogam has also played an important role in the establishment of traditional Korean medicine as a universally valid and original form of medicine, independent of traditional Chinese medicine. PMID- 27280044 TI - Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives. AB - OBJECTIVES: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the 'apicoplast', which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. METHODS: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. RESULTS: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle's function, which wouldimpede the survival of the parasite. CONCLUSION: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug resistance. PMID- 27280046 TI - IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms. AB - OBJECTIVES: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. METHODS: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM- 133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. RESULTS: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM- 133N was found to be significant and dose dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/ kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, beta-sitosterol, nonaeicosanol, beta-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. CONCLUSION: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders. PMID- 27280047 TI - The Place of Complementary Medicine in the Treatment of Autistic Children. AB - OBJECTIVES: The purpose of this study is to achieve a vision for autistic children and their parents aimed at generating interest in ideas such as "Sanitas Per Aquam" (SPA), massage and music therapy, which has begun to have widespread use and to attract attention. METHODS: This cross-sectional, descriptive study was carried out with autistic children and their parents from February to April 2015 in Mugla, Turkey. The study was began by interviewing experts in the field and by developing a suitable assessment questionnaire. In order to direct the flow of conversation between the researchers and the autisitc children and their parents, the researchers conducted semi-structured face to face interviews in a form that had been determined by using reports in the literature and the opinions of experts in the field. RESULTS: Forty two boys (84%) and eight girls (16%) with autism participated in our study. Children in the 0 ? 7 age group spent long time in the bathroom (P = 0.001). Boys liked to be hugged more than girls (P = 0.01). Children ages 0 ? 7 years liked bright lighting while those 15 years of age and older liked gloomy lighting (P = 0.009). Except for these statistically significant sex- and age-related differences, no other statistically significant differences were noted in the parameters of this study. Although the result was not statistically significant, more children with mild autism disorder obeyed commands like inhale or exhale (P = 0.051). CONCLUSION: Treatment for autism spectrum disorders is not yet fully possible, so many studies are being done to alleviate some symptoms and to improve the quality of life for individuals with autism and their families. As a result of our study, whether touching the areas the children want touched and listening to their favorite music are required to stimulate the brain remain as questions in our minds. PMID- 27280048 TI - Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target: -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer. AB - OBJECTIVES: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide- co-glycolide) (PLGA) nano encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo]undefined[a]pyrene (BaP)]-induced lung cancer in mice in vivo. METHODS: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. RESULTS: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. CONCLUSION: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer. PMID- 27280049 TI - Antifungal Activity of Bee Venom and Sweet Bee Venom against Clinically Isolated Candida albicans. AB - OBJECTIVES: The purpose of this study was to investigate the antifungal effect of bee venom (BV) and sweet bee venom (SBV) against Candida albicans (C. albicans) clinical isolates. METHODS: In this study, BV and SBV were examined for antifungal activities against the Korean Collection for Type Cultures (KCTC) strain and 10 clinical isolates of C. albicans. The disk diffusion method was used to measure the antifungal activity and minimum inhibitory concentration (MIC) assays were performed by using a broth microdilution method. Also, a killing curve assay was conducted to investigate the kinetics of the anti- fungal action. RESULTS: BV and SBV showed antifungal activity against 10 clinical isolates of C. albicans that were cultured from blood and the vagina by using disk diffusion method. The MIC values obtained for clinical isolates by using the broth microdilution method varied from 62.5 MUg/ mL to 125 MUg/mL for BV and from 15.63 MUg/mL to 62.5 MUg/mL for SBV. In the killing-curve assay, SBV behaved as amphotericin B, which was used as positive control, did. The antifungal efficacy of SBV was much higher than that of BV. CONCLUSION: BV and SBV showed antifungal activity against C. albicans clinical strains that were isolated from blood and the vagina. Especially, SBV might be a candidate for a new antifungal agent against C. albicans clinical isolates. PMID- 27280050 TI - Ethanol Extract of Oldenlandia diffusa - an Effective Chemotherapeutic for the Treatment of Colorectal Cancer in Humans: -Anti-Cancer Effects of Oldenlandia diffusa. AB - OBJECTIVES: Oldenlandia diffusa is traditionally used to relieve the symptoms of and to treat various diseases, but its anti-cancer activity has not been well studied. In the present study, the authors investigated the anti-cancer effects of an ethanol extract of Oldenlandia diffusa (EOD) on HT-29 human adenocarcinoma cells. METHODS: Cells were treated with different concentrations of an EOD, and cell death was assessed by using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) assay. Analyses of the sub G1 peak, the caspase 3 and -9 activities, and the mitochondrial membrane depolarizations were conducted to confirm cell death by apoptosis. Also, intracellular reactive oxygen species (ROS) generation was determined using carboxy-H2DCFDA (5-(and-6)-carboxy 20,70-dichlorodihydrofluorescein diacetate). RESULTS: EOD inhibited the proliferation of HT-29 cells for 24 hours by 78.6% +/- 8.1% at 50 MUg/mL, 74.4% +/- 4.6% at 100 MUg/mL, 65.9% +/- 5.2% at 200 MUg/mL, 51.4% +/- 6.2% at 300 MUg/mL, and by 41.7% +/- 8.9% at 400 MUg/mL, and treatment for 72 hours reduced the proliferation at the corresponding concentrations by 43.3% +/- 8.8%, 24.3 +/- 5.1 mV, 13.5 +/- 3.2 mV, 6.5 +/- 2.3 mV, and by 2.6 +/- 2.3 mV. EOD increased the number of cells in the sub-G1 peak in a dose-dependent manner. The mitochondrial membrane depolarization was elevated by EOD. Also, caspase activities were dose dependently elevated in the presence of EOD, and these activities were repressed by a pan-caspase inhibitor (zVAD-fmk). The ROS generation was significantly increased by EOD and N-acetyl-L-cysteine (NAC; a ROS scavenger) remarkably abolished EOD-induced cell death. In addition, a combination of sub-optimal doses of EOD and chemotherapeutic agents noticeably suppressed the growth of HT-29 cancer cells. CONCLUSION: These results indicate that EOD might be an effective chemotherapeutic for the treatment of human colorectal cancer. PMID- 27280051 TI - Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1. AB - OBJECTIVES: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, H2O2) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. METHODS: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and H2O2 in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and H2O2-induced growth inhibition. RESULTS: The results showed that EGL effectively inhibited H2O2 induced growth and the generation of ROS. EGL markedly suppressed H2O2-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 (p gammaH2AX), a widely used marker of DNA damage, suggesting that EGL prevented H2O2-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against H2O2-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. CONCLUSION: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from H2O2-induced oxidative cytotoxicity. PMID- 27280052 TI - Ethanol Extracts of Achillea millefolium and Hypericum perforatum Low Anti Toxoplasma Activity. AB - OBJECTIVES: This study was performed to determine the lethal and the inhibitory effects of ethanol extracts of Achillea millefolium (A. millefolium) and Hypericum perforatum (H. perforatum) on Toxoplasma gondii (T. gondii) RH strain tachyzoites in vitro. METHODS: The tachyzoites were treated with concentrations of 10, 50, and 100 mg/mL of A. millefolium and H. perforatum extracts within 10, 30, and 45 minutes in the wells. The mortality rates of tachyzoites treated with extracts were determined by using alkaline methylene blue staining. Also, the tachyzoites in cell cultures were treated with concentrations of 50, 100, and 200 mg/mL of these extracts. The cell viability, inhibition concentration (IC50), and selectivity were determined from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assays. RESULTS: In the cell-free in vitro study, all of tachyzoites were killed at concentrations of 100 mg/mL of both extracts while at concentration 10 mg/mL, the mortality was 4.53% - 5.31%. In the cell culture study, the values of the effective concentration (EC50) were 215 and 153 MUg/mL and the selectivities were 0.73 and 0.69 for the A. millefolium and the H. perforatum extracts, respectively. CONCLUSION: We conclude that neither extracts has any significant effect on the tachyzoites of T. gondii in cell cultures. PMID- 27280053 TI - Erratum: Are there a guidelines for implantable spinal cord stimulator therapy in patients using chronic anticoagulation therapy? - A review of decision-making in the high-risk patient. AB - [This corrects the article on p. 33 in vol. 7, PMID: 27127698.]. PMID- 27280054 TI - Erratum: A rare intracranial tumor consisting of malignant anaplastic and papillary meningioma subtypes. AB - [This corrects the article on p. 21 in vol. 7, PMID: 26981322.]. PMID- 27280056 TI - I slew the beast! PMID- 27280055 TI - Spontaneous shrinkage of vestibular schwannoma. AB - BACKGROUND: "Watch, wait, and rescan" (WWR) has an established place as a successful management option for a significant proportion of vestibular schwannomas (VS) as an alternative to microsurgical removal or stereotactic radiotherapy. VS may grow slowly and continuously, followed by stagnation or even shrinkage. We present two case reports of spontaneous shrinkage of VS along with a review of the literature. CASE DESCRIPTION: A 29-year-old female presented with a progressive history of visual blurring and intermittent diplopia over 2 months. A 29 mm of maximum intracranial diameter (ICD) VS with secondary obstructive hydrocephalus was diagnosed. The patient underwent a ventriculo-peritoneal shunt with resolution of her symptoms and opted for initial WWR management. Interval scanning between 2007 and 2014 showed progressive reduction in the maximum ICD together with reduction in the degree of central tumor enhancement. Maximum ICD at most recent follow up was 22 mm. A 28-year-old female was referred with right sensorineural deafness. A right VS of maximum ICD of 27 mm was diagnosed. Initial WWR management was planned after discussion. Serial imaging showed an initial increase in the size of the tumor followed by progressive reduction in size. The most recent follow up showed a maximum ICD of 20 mm. CONCLUSION: Early WWR management can be associated with spontaneous shrinkage of VS over time. Prospective clinical study of larger numbers of such cases using the UK VS database may help to identify predictive factors for the spontaneous regression of VS. PMID- 27280057 TI - An aggressive multidisciplinary approach reduces mortality in rhinocerebral mucormycosis. AB - BACKGROUND: Rhinocerebral mucormycosis occurs in immunocompromised hosts with uncontrolled diabetes, solid organ transplants, and hematologic malignancies. Primary disease is in the paranasal sinuses but often progresses intracranially, via direct extension or angioinvasion. Rhinocerebral mucormycosis is rapidly fatal with a mortality rate of 85%, even when maximally treated with surgical debridement, antifungal therapy, and correction of underlying processes. METHODS: We performed a retrospective chart review of patients with rhinocerebral mucormycosis from 2011 to 2014. These patients were analyzed for symptoms, surgical and medical management, and outcome. We found four patients who were diagnosed with rhinocerebral mucormycosis. All patients underwent rapid aggressive surgical debridement and were started on antifungal therapy on the day of diagnosis. Overall, we observed a mortality rate of 50%. RESULTS: An early aggressive multidisciplinary approach with surgical debridement, antifungal therapy, and correction of underlying disease have been shown to improve survivability in rhinocerebral mucormycosis. CONCLUSION: A multidisciplinary approach to rhinocerebral mucormycosis with otolaryngology, neurosurgery, and ophthalmology, infectious disease and medical intensivists can help reduce mortality in an otherwise largely fatal disease. Even despite these measures, outcomes remain poor, and a high index of suspicion must be maintained in at-risk populations, in order to rapidly execute a multifaceted approach. PMID- 27280058 TI - Role of Biosensing Technology for NeuroAIDS Management. PMID- 27280059 TI - Comparison of an Atomic Model and Its Cryo-EM Image at the Central Axis of a Helix. AB - Cryo-electron microscopy (cryo-EM) is an important biophysical technique that produces three-dimensional (3D) density maps at different resolutions. Because more and more models are being produced from cryo-EM density maps, validation of the models is becoming important. We propose a method for measuring local agreement between a model and the density map using the central axis of the helix. This method was tested using 19 helices from cryo-EM density maps between 5.5 A and 7.2 A resolution and 94 helices from simulated density maps. This method distinguished most of the well-fitting helices, although challenges exist for shorter helices. PMID- 27280060 TI - Fluorescent property of indocyanine green (ICG) rubber ring using LED and laser light sources. AB - Fluorescent properties of ICG depends on solvent. Fluorescent characteristics of ICG rubber rings and optimized detection system condition were identified. The fluorescent rubber rings are produced by drying mixture of ICG solution and liquid rubber. LED and laser light sources were used to test differences between them. Other variables are ICG molar concentration (100, 80, 60, 40, 20, 10MUM), excitation light spectrum (740, 760, 785nm) and angle of view (0~80 degrees ). We observed that ICG ring emitted fluorescence at longer wavelength than in blood and aqueous state. Observation angle between 0 and 50 provided similar brightness of images, while others are significantly less luminous. Excitation light between 740~760nm ensured non-overlapping spectrums of excitation light and fluorescence emission. PMID- 27280061 TI - Zika Virus, Elevation, and Transmission Risk. AB - INTRODUCTION: Zika virus has appeared in the Americas in the form of a major outbreak, and is now known to cause birth defects when pregnant women are infected. As a result, the Centers for Disease Control and Prevention issued travel guidelines, in the form of an elevational risk definition: destinations below 2000m are considered as at-risk. METHODS: We explored the distribution of known Zika virus vector mosquito species in relation to climatic conditions, elevation, latitude, and air traffic connections to the United States. RESULTS: In view of the tropical and subtropical nature of the mosquito species that are the primary Zika virus vectors, we point out that climate varies rather dramatically with respect to elevation and latitude, such that a single elevational criterion will be a poor predictor of potential for transmission. DISCUSSION: We suggest an initial adjustment would consider latitude in addition to elevation; a more definitive, quantitative analysis of risk would consider variables of ecology, climate, human condition, and connectivity of areas. PMID- 27280062 TI - Right Ventricular Myocardial Ischemia with Arrhythmia in an Asphyxiated Newborn. AB - Background Infant and neonatal myocardial infarction (MI) has been described in association with congenital heart disease, coronary artery abnormalities, myocarditis, and tumors. MI in the perinatal period in a structurally normal heart and with ventricular arrhythmia as a presenting feature has not been thoroughly described. Published case reports describe treatment methods extrapolated from adult MI. However, due to the rare occurrence, the most appropriate acute treatment for both MI and ventricular arrhythmia in newborn infants remains unknown. Case A male term infant with perinatal asphyxia and need for extensive cardiopulmonary resuscitation at birth had ventricular tachyarrhythmia and ST-elevations on electrocardiogram. Four hours after birth, he died from cardiogenic failure. A thrombus at the right coronary artery was found on autopsy. Conclusion MI in the perinatal period in a structurally normal heart is very rare and mortality is high. Although acute treatments extrapolated from adult MI has been described to result in favorable outcomes in newborn infants, guidelines are lacking on how to manage acute MI and associated ventricular arrhythmia. PMID- 27280063 TI - The Effect of a Universal Cervical Length Screening Program on Antepartum Management and Birth Outcomes. AB - Objective The objective of this study was to evaluate the effect of a universal cervical length screening program on the incidence of antepartum interventions. Study Design This retrospective cohort study included women delivering >= 20 weeks of gestation with singleton pregnancies before and after implementing universal cervical length screening. Antepartum interventions included admission for threatened preterm birth, >= 2 cervical length measurements, cervical cerclage, neonatology consultation, betamethasone, antibiotic administration for preterm premature rupture of membranes, and tocolysis. Results There were 1,131 women-506 before the screening program (unexposed) and 625 afterward (exposed). The screening program resulted in significantly more women screened (3.0 vs. 69.9%, p < 0.0001). The exposed group was more likely to undergo >= 1 intervention (20.0 vs. 9.5%, p < 0.0001); specifically, admission for threatened preterm birth (3.8 vs. 1.8%, p = 0.04) and >= 2 cervical measurements (11.2 vs. 2.0%, p < 0.001). Other interventions were similar between groups (all p >= 0.06). Median gestation length was significantly longer in the exposed (39.6 weeks [interquartile, IQR: 38.6-40.4] vs. 39.0 weeks [IQR: 38.0-40.0, p < 0.001]); however, preterm delivery incidence was unaffected (9.4 vs. 10.9%, p = 0.43). Remaining neonatal outcomes were similar (all p >= 0.14). Conclusion Implementing universal cervical length screening significantly increased the proportion of women undergoing >= 1 antepartum intervention. With the exception of a modestly prolonged gestation, other outcomes were unaffected. PMID- 27280064 TI - A Narrative Review of Pharmacologic and Non-pharmacologic Interventions for Disorders of Consciousness Following Brain Injury in the Pediatric Population. AB - Traumatic brain injury (TBI) is the most common cause of long-term disability in the United States. A significant proportion of children who experience a TBI will have moderate or severe injuries, which includes a period of decreased responsiveness. Both pharmacological and non-pharmacological modalities are used for treating disorders of consciousness after TBI in children. However, the evidence supporting the use of potential therapies is relatively scant, even in adults, and overall, there is a paucity of study in pediatrics. The goal of this review is to describe the state of the science for use of pharmacologic and non pharmacologic interventions for disorders of consciousness in the pediatric population. PMID- 27280066 TI - Potential problems of removing one invasive species at a time: a meta-analysis of the interactions between invasive vertebrates and unexpected effects of removal programs. AB - Although the co-occurrence of nonnative vertebrates is a ubiquitous global phenomenon, the study of interactions between invaders is poorly represented in the literature. Limited understanding of the interactions between co-occurring vertebrates can be problematic for predicting how the removal of only one invasive-a common management scenario-will affect native communities. We suggest a trophic food web framework for predicting the effects of single-species management on native biodiversity. We used a literature search and meta-analysis to assess current understanding of how the removal of one invasive vertebrate affects native biodiversity relative to when two invasives are present. The majority of studies focused on the removal of carnivores, mainly within aquatic systems, which highlights a critical knowledge gap in our understanding of co occurring invasive vertebrates. We found that removal of one invasive vertebrate caused a significant negative effect on native species compared to when two invasive vertebrates were present. These unexpected results could arise because of the positioning and hierarchy of the co-occurring invasives in the food web (e.g., carnivore-carnivore or carnivore-herbivore). We consider that there are important knowledge gaps to determinate the effects of multiple co-existing invaders on native ecosystems, and this information could be precious for management. PMID- 27280065 TI - Association of potential salivary biomarkers with diabetic retinopathy and its severity in type-2 diabetes mellitus: a proteomic analysis by mass spectrometry. AB - AIM/HYPOTHESIS: The aim of our study was to characterize the human salivary proteome and determine the changes in protein expression in two different stages of diabetic retinopathy with type-2 diabetes mellitus: (1) with non-proliferative diabetic retinopathy (NPDR) and (2) with proliferative diabetic retinopathy (PDR). Type-2 diabetes mellitus without diabetic retinopathy (XDR) was designated as control. METHOD: In this study, 45 saliva samples were collected (15 samples from XDR control group, 15 samples from NPDR disease group and 15 samples from PDR disease group). Salivary proteins were extracted, reduced, alkylated, trypsin digested and labeled with an isobaric tag for relative and absolute quantitation (iTRAQ) before being analyzed by an Orbitrap fusion tribrid mass spectrometer. Protein annotation, fold change calculation and statistical analysis were interrogated by Proteome Discoverer. Biological pathway analysis was performed by Ingenuity Pathway Analysis. Data are available via ProteomeXchange with identifiers PXD003723-PX003725. RESULTS: A total of 315 proteins were identified from the salivary proteome and 119 proteins were found to be differentially expressed. The differentially expressed proteins from the NPDR disease group and the PDR disease group were assigned to respective canonical pathways indicating increased Liver X receptor/Retinoid X receptor (LXR/RXR) activation, Farnesoid X receptor/Retinoid X receptor (FXR/RXR) activation, acute phase response signaling, sucrose degradation V and regulation of actin-based motility by Rho in the PDR disease group compared to the NPDR disease group. CONCLUSIONS/INTERPRETATION: Progression from non-proliferative to proliferative retinopathy in type-2 diabetic patients is a complex multi-mechanism and systemic process. Furthermore, saliva was shown to be a feasible alternative sample source for diabetic retinopathy biomarkers. PMID- 27280067 TI - Living to the range limit: consumer isotopic variation increases with environmental stress. AB - BACKGROUND: Theoretically, each species' ecological niche is phylogenetically determined and expressed spatially as the species' range. However, environmental stress gradients may directly or indirectly decrease individual performance, such that the precise process delimiting a species range may not be revealed simply by studying abundance patterns. In the intertidal habitat the vertical ranges of marine species may be constrained by their abilities to tolerate thermal and desiccation stress, which may act directly or indirectly, the latter by limiting the availability of preferred trophic resources. Therefore, we expected individuals at greater shore heights to show greater variation in diet alongside lower indices of physiological condition. METHODS: We sampled the grazing gastropod Echinolittorina peruviana from the desert coastline of northern Chile at three shore heights, across eighteen regionally-representative shores. Stable isotope values (delta13C and delta15N) were extracted from E. peruviana and its putative food resources to estimate Bayesian ellipse area, carbon and nitrogen ranges and diet. Individual physiological condition was tracked by muscle % C and % N. RESULTS: There was an increase in isotopic variation at high shore levels, where E. peruviana's preferred resource, tide-deposited particulate organic matter (POM), appeared to decrease in dietary contribution, and was expected to be less abundant. Both muscle % C and % N of individuals decreased with height on the shore. DISCUSSION: Individuals at higher stress levels appear to be less discriminating in diet, likely because of abiotic forcing, which decreases both consumer mobility and the availability of a preferred resource. Abiotic stress might be expected to increase trophic variation in other selective dietary generalist species. Where this coincides with a lower physiological condition may be a direct factor in setting their range limit. PMID- 27280068 TI - Assessing Illumina technology for the high-throughput sequencing of bacteriophage genomes. AB - Bacteriophages are the most abundant biological entities on the planet, playing crucial roles in the shaping of bacterial populations. Phages have smaller genomes than their bacterial hosts, yet there are currently fewer fully sequenced phage than bacterial genomes. We assessed the suitability of Illumina technology for high-throughput sequencing and subsequent assembly of phage genomes. In silico datasets reveal that 30* coverage is sufficient to correctly assemble the complete genome of ~98.5% of known phages, with experimental data confirming that the majority of phage genomes can be assembled at 30* coverage. Furthermore, in silico data demonstrate it is possible to co-sequence multiple phages from different hosts, without introducing assembly errors. PMID- 27280069 TI - Long-term oncologic outcomes of laparoscopic nephroureterectomy versus open nephroureterectomy for upper tract urothelial carcinoma: a systematic review and meta-analysis. AB - Background. Several factors have been validated as predictors of disease recurrence in upper tract urothelial carcinoma. However, the oncological outcomes between different surgical approaches (open nephroureterectomy versus laparoscopic nephroureterectomy, ONU vs LNU) remain controversial. Therefore, we performed a meta-analysis to evaluate the oncological outcomes associated with different surgical approaches. Methods. We conducted an electronic search of the PubMed, Embase, ISI Web of Knowledge and Cochrane Library electronic databases through November 2015, screened the retrieved references, collected and evaluated the relevant information. We extracted and synthesized the corresponding hazard ratios (HRs) and 95% confidence intervals (95% CI) using Stata 13. Results. Twenty-one observational studies were eligible for inclusion in the meta analysis. The results of the meta-analysis showed no differences in the intravesical recurrence-free survival (IRFS), unspecified recurrence-free survival (UnRFS) and overall survival (OS) between LNUandONU. However, improvements in the extravesical recurrence free survival (ExRFS) and cancer specific survival (CSS) were observed inLNU. The pooled hazard ratios were 1.05 (95% CI [0.92-1.18]) for IRFS, 0.80 (95% CI [0.64-0.96]) for ExRFS, 1.10 (95% CI [0.93-1.28]) for UnRFS, 0.91 (95% CI [0.66-1.17]) for OS and 0.79 (95% CI [0.68 0.91]) for CSS. Conclusion. Based on current evidence, LNU could provide equivalent prognostic effects for upper tract urothelial carcinoma, and had better oncological control of ExRFS and CSS compared to ONU. However, considering all eligible studies with the intrinsic bias of retrospective study design, the results should be interpreted with caution. Prospective randomized trials are needed to verify these results. PMID- 27280070 TI - Microfungal oasis in an oligotrophic desert: diversity patterns and community structure in three freshwater systems of Cuatro Cienegas, Mexico. AB - The Cuatro Cienegas Basin (CCB) comprises several oligotrophic aquatic ecosystems limited by phosphorus. These aquatic systems are dominated by a high prokaryotic diversity, shaped by the stress of low nutrient supplies and interspecific competition. Although fungi constitute a diverse and important component of microbial diversity, the microfungal diversity in the CCB remains to be unveiled. With the aim to explore microfungal diversity and ecological patterns in this area, we present the first investigation analyzing cultivable taxa from sediment and water, as well as lignocellulolytic taxa obtained from incubated submerged plant debris, and wood panels in three contrasting freshwater systems in the CCB: Churince, Becerra and Pozas Rojas. We chose a culture-based approach to analyze sediment and water samples in order to obtain fungal cultures, providing opportunities for a posteriori studies, and the possibility of ex situ preservation of the diversity. We evaluated sequence data from the nuclear ribosomal internal transcribed spacer including the 5.8 rDNA region for 126 isolates, revealing 37 OTUs. These OTUs were phylogenetically affiliated to several genera in the fungal phyla: Zygomycota, Basidiomycota, and Ascomycota. We recorded two OTUs with saline affinity, agreeing with previous findings on the prokaryotic communities with ancestral marine resemblances. All the studied systems showed moderate diversity levels, however discrepancies among the diversity indexes were observed, due to the occurrence of abundant taxa in the samples. Our results indicated that lignocellulolytic microfungal communities are dominated by transient fungal taxa, as resident species were not recorded perhaps as a result of the long-term strong competition with the highly adapted prokaryotic community. Moreover, the obtained microfungal taxa occurred mostly on the resident plant debris, rather than submerged wood panels, perhaps as a result of the high adaptation to specific environmental conditions. In conclusion, the CCB possess a moderate taxonomical diversity compared to other arid environments, probably as a result of high selective pressures. Nonetheless, due to high spatial and temporal heterogeneity, the functional fungal diversity was considerable as predicted by the intermediate disturbance hypothesis. Decisively, the assessment of microfungal diversity freshwater systems is relevant, since this ecological group of microorganisms represents an important indicator of trophic complexity and biotic interactions among microbial communities, having important implications for understanding eukaryotic survival at the oligotrophic limit for life. PMID- 27280071 TI - Snapshot fecal survey of domestic animals in rural Ghana for Mycobacterium ulcerans. AB - Identifying the source reservoirs of Mycobacterium ulcerans is key to understanding the mode of transmission of this pathogen and controlling the spread of Buruli ulcer (BU). In Australia, the native possum can harbor M. ulcerans in its gastrointestinal tract and shed high concentrations of the bacteria in its feces. To date, an analogous animal reservoir in Africa has not been identified. Here we tested the hypothesis that common domestic animals in BU endemic villages of Ghana are reservoir species analogous to the Australian possum. Using linear-transects at 10-meter intervals, we performed systematic fecal surveys across four BU endemic villages and one non-endemic village in the Asante Akim North District of Ghana. One hundred and eighty fecal specimens from a single survey event were collected and analyzed by qPCR for the M. ulcerans diagnostic DNA targets IS2404 and KR-B. Positive and negative controls performed as expected but all 180 test samples were negative. This structured snapshot survey suggests that common domestic animals living in and around humans do not shed M. ulcerans in their feces. We conclude that, unlike the Australian native possum, domestic animals in rural Ghana are unlikely to be major reservoirs of M. ulcerans. PMID- 27280072 TI - European adults' physical activity socio-demographic correlates: a cross sectional study from the European Social Survey. AB - Background. From a public health perspective, the study of socio-demographic factors related to physical activity is important in order to identify subgroups for intervention programs. Objective. This study aimed to identify the prevalence of, and the socio-demographic correlates related to, the achievement of recommended physical activity levels. Methods. Using data from the European Social Survey round 6, physical activity and socio-demographic characteristics were collected, in 2012, from 39,278 European adults (18,272 men, 21,006 women), aged 18-65 years, from 28 countries. The question of meeting physical activity guidelines was assessed using World Health Organization criteria. Results. A total of 64.50% (63.36% men, 66.49% women) attained physical activity recommended levels. The likelihood of attaining physical activity recommendations was higher in the 55-64 years age group (men: OR = 1.22, p < 0.05; women: OR = 1.66, p < 0.001), among those who had secondary education (men: OR = 1.28, p < 0.01; women: OR = 1.26, p < 0.05), among those who lived in rural areas (men: OR = 1.20, p < 0.001; women: OR = 1.10, p < 0.05), and among those who had three or more people living at home (men: OR = 1.40, p < 0.001; women: OR = 1.43, p < 0.001). On the other hand, attaining physical activity recommendations was negatively associated with being unemployed (men: OR = 0.70, p < 0.001; women: OR = 0.87, p < 0.05), being a student (OR = 0.56, p < 0.001; women: OR = 0.64, p < 0.01), being a retired person (men: OR = 0.86, p < 0.05) and with having a higher household income (OR = 0.80, p < 0.001; women: OR = 0.81, p < 0.01). Conclusions. This research helped clarify that, as the promotion of physical activity is critical to sustain health and prevent disease, socio-demographic factors are important to consider when planning the increase of physical activity. PMID- 27280073 TI - A closer look at four-dot masking of a foveated target. AB - Four-dot masking with a common onset mask was recently demonstrated in a fully attended and foveated target (Filmer, Mattingley & Dux, 2015). Here, we replicate and extend this finding by directly comparing a four-dot mask with an annulus mask while probing masking as a function of mask duration, and target-mask separation. Our results suggest that while an annulus mask operates via spatially local contour interactions, a four-dot mask operates through spatially global mechanisms. We also measure how the visual system's representation of an oriented bar is impacted by a four-dot mask, and find that masking here does not degrade the precision of perceived targets, but instead appears to be driven exclusively by rendering the target completely invisible. PMID- 27280074 TI - Experimental warming decreases arbuscular mycorrhizal fungal colonization in prairie plants along a Mediterranean climate gradient. AB - BACKGROUND: Arbuscular mycorrhizal fungi (AMF) provide numerous services to their plant symbionts. Understanding climate change effects on AMF, and the resulting plant responses, is crucial for predicting ecosystem responses at regional and global scales. We investigated how the effects of climate change on AMF-plant symbioses are mediated by soil water availability, soil nutrient availability, and vegetation dynamics. METHODS: We used a combination of a greenhouse experiment and a manipulative climate change experiment embedded within a Mediterranean climate gradient in the Pacific Northwest, USA to examine this question. Structural equation modeling (SEM) was used to determine the direct and indirect effects of experimental warming on AMF colonization. RESULTS: Warming directly decreased AMF colonization across plant species and across the climate gradient of the study region. Other positive and negative indirect effects of warming, mediated by soil water availability, soil nutrient availability, and vegetation dynamics, canceled each other out. DISCUSSION: A warming-induced decrease in AMF colonization would likely have substantial consequences for plant communities and ecosystem function. Moreover, predicted increases in more intense droughts and heavier rains for this region could shift the balance among indirect causal pathways, and either exacerbate or mitigate the negative, direct effect of increased temperature on AMF colonization. PMID- 27280075 TI - Rapidly increasing macroalgal cover not related to herbivorous fishes on Mesoamerican reefs. AB - Long-term phase shifts from coral to macroalgal dominated reef systems are well documented in the Caribbean. Although the impact of coral diseases, climate change and other factors is acknowledged, major herbivore loss through disease and overfishing is often assigned a primary role. However, direct evidence for the link between herbivore abundance, macroalgal and coral cover is sparse, particularly over broad spatial scales. In this study we use a database of coral reef surveys performed at 85 sites along the Mesoamerican Reef of Mexico, Belize, Guatemala and Honduras, to examine potential ecological links by tracking site trajectories over the period 2005-2014. Despite the long-term reduction of herbivory capacity reported across the Caribbean, the Mesoamerican Reef region displayed relatively low macroalgal cover at the onset of the study. Subsequently, increasing fleshy macroalgal cover was pervasive. Herbivorous fish populations were not responsible for this trend as fleshy macroalgal cover change was not correlated with initial herbivorous fish biomass or change, and the majority of sites experienced increases in macroalgae browser biomass. This contrasts the coral reef top-down herbivore control paradigm and suggests the role of external factors in making environmental conditions more favourable for algae. Increasing macroalgal cover typically suppresses ecosystem services and leads to degraded reef systems. Consequently, policy makers and local coral reef managers should reassess the focus on herbivorous fish protection and consider complementary measures such as watershed management in order to arrest this trend. PMID- 27280076 TI - Are mountain habitats becoming more suitable for generalist than cold-adapted lizards thermoregulation? AB - Mountain lizards are highly vulnerable to climate change, and the continuous warming of their habitats could be seriously threatening their survival. We aim to compare the thermal ecology and microhabitat selection of a mountain lizard, Iberolacerta galani, and a widely distributed lizard, Podarcis bocagei, in a montane area. Both species are currently in close syntopy in the study area, at 1,400 m above the sea level. We determined the precision, accuracy and effectiveness of thermoregulation, and the thermal quality of habitat for both species. We also compared the selection of thermal microhabitats between both species. Results show that I. galani is a cold-adapted thermal specialist with a preferred temperature range of 27.9-29.7 degrees C, while P. bocagei would be a thermal generalist, with a broader and higher preferred temperature range (30.1 34.5 degrees C). In addition, I. galani selects rocky substrates while P. bocagei selects warmer soil and leaf litter substrates. The thermal quality of the habitat is higher for P. bocagei than for I. galani. Finally, P. bocagei achieves a significantly higher effectiveness of thermoregulation (0.87) than I. galani (0.80). Therefore, these mountain habitat conditions seem currently more suitable for performance of thermophilic generalist lizards than for cold specialist lizards. PMID- 27280077 TI - Emotional competence relating to perceived stress and burnout in Spanish teachers: a mediator model. AB - This study examined direct associations between emotional competence, perceived stress and burnout in 489 Spanish teachers. In addition, a model in which perceived stress mediated pathways linking emotional competence to teacher burnout symptoms was also examined. Results showed that emotional competence and stress were significantly correlated with teacher burnout symptoms in the expected direction. Moreover, mediational analysis indicated that perceived stress partly mediated the relationship between emotional competence and the three dimensions of burnout even when controlling for salient background characteristics. These findings suggest an underlying process by which high emotional competence may increase the capacity to cope with symptoms of burnout, by reducing the experience of stress. Implications of these findings for future research and for working with teachers to prevent burnout are discussed. PMID- 27280078 TI - An explicit-solvent conformation search method using open software. AB - Computer modeling is a popular tool to identify the most-probable conformers of a molecule. Although the solvent can have a large effect on the stability of a conformation, many popular conformational search methods are only capable of describing molecules in the gas phase or with an implicit solvent model. We have developed a work-flow for performing a conformation search on explicitly-solvated molecules using open source software. This method uses replica exchange molecular dynamics (REMD) to sample the conformational states of the molecule efficiently. Cluster analysis is used to identify the most probable conformations from the simulated trajectory. This work-flow was tested on drug molecules alpha-amanitin and cabergoline to illustrate its capabilities and effectiveness. The preferred conformations of these molecules in gas phase, implicit solvent, and explicit solvent are significantly different. PMID- 27280079 TI - Uropygial gland and bib colouration in the house sparrow. AB - Birds frequently signal different qualities by plumage colouration, mainly during mating. However, plumage colouration is determined during the moult, and therefore it would indicate the quality of individual birds during the moult, not its current quality. Recent studies, however, suggest that birds could modify plumage colouration by using cosmetic preen oil produced by the uropygial gland. In this study, I show that bib colouration is related to uropygial gland size and body condition in male house sparrows (Passer domesticus). Moreover, I conducted an experiment in which a group of sparrows were inoculated with an antigen, mimicking an illness. In control birds, short-term changes in bib colouration were related to both body condition and change in uropygial gland size. Therefore, birds that reduced uropygial gland size showed a greater colouration change. However, bib colouration did not change with the change in uropygial gland size in experimental birds inoculated with the antigen. Given that the experiment did not affect preen oil production or consumption, this finding tentatively suggests that the immune challenge provoked a change in the composition of preen oil, affecting its cosmetic properties. In short, the results of this study suggest that (1) male house sparrows produce cosmetic preen oil that alters the colouration of their bibs; (2) the more change in uropygial gland size, the more change in bib colouration; and (3) in this way, bib colouration has the potential to signal current health status, since less healthy birds showed less capacity to change bib colouration. PMID- 27280080 TI - Early Graft Dysfunction in Living Donor Liver Transplantation and the Small for Size Syndrome. AB - LDLT has arisen as a viable means to reduce waitlist mortality. However, its widespread embrace by the liver transplant community has been met with frustration centered on donor morbidity and small-for-size-syndrome. Focusing on the later entity, we describe the initial recognition of this early graft dysfunction, the theorized pathophysiology and solutions to remedy its emergence. PMID- 27280081 TI - Nutrient-Deprived Retinal Progenitors Proliferate in Response to Hypoxia: Interaction of the HIF-1 and mTOR Pathway. AB - At a cellular level, nutrients are sensed by the mechanistic Target of Rapamycin (mTOR). The response of cells to hypoxia is regulated via action of the oxygen sensor Hypoxia-Inducible Factor 1 (HIF-1). During development, injury and disease, tissues might face conditions of both low nutrient supply and low oxygen, yet it is not clear how cells adapt to both nutrient restriction and hypoxia, or how mTOR and HIF-1 interact in such conditions. Here we explore this question in vivo with respect to cell proliferation using the ciliary marginal zone (CMZ) of Xenopus. We found that both nutrient-deprivation and hypoxia cause retinal progenitors to decrease their proliferation, yet when nutrient-deprived progenitors are exposed to hypoxia there is an unexpected rise in cell proliferation. This increase, mediated by HIF-1 signalling, is dependent on glutaminolysis and reactivation of the mTOR pathway. We discuss how these findings in non-transformed tissue may also shed light on the ability of cancer cells in poorly vascularised solid tumours to proliferate. PMID- 27280082 TI - Demographic and angiographic profile in premature cases of acute coronary syndrome: analysis of 820 young patients from South India. AB - BACKGROUND: Prevalence of acute coronary syndrome in young individuals is increasing progressively. Previous studies have focused on the analysis of risk factors and to some extent coronary angiographic profile in young vs. old patients with acute coronary syndrome, but no study compared the angiographic profile in young patients based on the type of acute coronary syndrome. So, this study was conducted to determine the differences in demographic and coronary angiographic profile of young patients with ST-elevated myocardial infarction (STEMI) vs. those with non-ST-elevated myocardial infarction (NSTEMI) or unstable angina (UA). METHODS: We retrospectively analyzed young patients (age <40 years) with acute coronary syndrome who underwent coronary angiography at Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru, India between April 2010 and March 2011. Coronary risk factor profile and angiographic features were compared between STEMI and NSTEMI/UA patients. RESULTS: Of 8,268 patients who underwent coronary angiography during the study period, 820 (~10%) were <=40 year age. Of them, 611 exhibited STEMI and 209 exhibited NSTEMI/UA. Angiographic analysis revealed that single-vessel disease was significantly more common in the STEMI group (56.6% vs. 36.6% respectively; P<0.001) whereas triple-vessel disease was significantly more common in the NSTEMI/UA group (3.6% vs. 10.5% respectively; P<0.001). Conversely, left anterior descending coronary artery was more commonly involved in the STEMI group (55.3% vs. 40.2% respectively; P<0.001), whereas left circumflex coronary artery was more commonly involved in the NSTEMI/UA group (11.8 vs. 23.4% respectively; P<0.001). Of note, smoking/tobacco consumption was the most significant coronary risk factor with prevalence as high as 65% in both groups. CONCLUSIONS: In the present study, significant differences were observed in coronary risk factor profile and angiographic features between young patients with STEMI and NSTEMI/UA. Larger studies will be required to establish specific associations between presentation of acute coronary syndromes and angiographic profiles in young patients. PMID- 27280083 TI - Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest. AB - BACKGROUND: Patients admitted to the hospital after primarily successful cardiopulmonary resuscitation (CPR) are at a very high risk for neurologic deficits and death. Targeted temperature management (TTM) for mild therapeutic hypothermia has been shown to improve survival compared to standard treatment. Acute cardiovascular events, such as myocardial infarction (MI), are a major cause for cardiac arrest (CA) in patients who undergo CPR. Recent findings have demonstrated the importance and impact of the leukocyte response following acute MI. METHODS: In this retrospective, single center study we enrolled 169 patients with CA due to non-traumatic causes and primarily successful CPR. A total of 111 subjects (66%) underwent TTM aiming for a target temperature of 32-34 degrees C. RESULTS: Analysis of 30 day follow up showed a significantly improved survival of all patients who received TTM compared to patients without hypothermia (P=0.0001). Furthermore TTM was an independent variable of good neurological outcome after 6 months (P=0.0030). Therapeutic hypothermia was found to be beneficial independent of differences in age and sex between both groups. While a higher rate of pneumonia was observed with TTM, this diagnosis had no additional impact on survival or neurological outcome. The beneficial effect on mortality remained significant in patients with the diagnosis of an acute cardiac event (P=0.0145). Next, we evaluated the kinetics of leukocytes in this group over the course of 7 days after CA. At presentation, patients showed a mean level of 16.5+/-6.7 of leukocytes per microliter. While this level stayed stable in the group of patients without hypothermia, patients who received TTM showed a significant decline of leukocyte levels resulting in significantly lower numbers of leukocytes on days 3 and 5 after CPR. Interestingly, these differences in leukocyte counts remained beyond the time period of TTM while C-reactive protein (CRP) levels were suppressed only during ongoing cooling, but differences between the groups were diminished after TTM was terminated (from day 3 on, P>0.2). Finally, patients who received TTM and showed a leukocyte count of less than 12.7/uL on day 3 had an improved survival (P=0.0214) and neurological outcome (P=0.0049) compared to patients above that level. CONCLUSIONS: Our data underline the beneficial effects of TTM and demonstrate an impact of hypothermia on leukocyte counts after CA. PMID- 27280084 TI - Numerical analysis of the effect of turbulence transition on the hemodynamic parameters in human coronary arteries. AB - BACKGROUND: Local hemodynamics plays an important role in atherogenesis and the progression of coronary atherosclerosis disease (CAD). The primary biological effect due to blood turbulence is the change in wall shear stress (WSS) on the endothelial cell membrane, while the local oscillatory nature of the blood flow affects the physiological changes in the coronary artery. In coronary arteries, the blood flow Reynolds number ranges from few tens to several hundreds and hence it is generally assumed to be laminar while calculating the WSS calculations. However, the pulsatile blood flow through coronary arteries under stenotic condition could result in transition from laminar to turbulent flow condition. METHODS: In the present work, the onset of turbulent transition during pulsatile flow through coronary arteries for varying degree of stenosis (i.e., 0%, 30%, 50% and 70%) is quantitatively analyzed by calculating the turbulent parameters distal to the stenosis. Also, the effect of turbulence transition on hemodynamic parameters such as WSS and oscillatory shear index (OSI) for varying degree of stenosis is quantified. The validated transitional shear stress transport (SST) k omega model used in the present investigation is the best suited Reynolds averaged Navier-Stokes turbulence model to capture the turbulent transition. The arterial wall is assumed to be rigid and the dynamic curvature effect due to myocardial contraction on the blood flow has been neglected. RESULTS: Our observations shows that for stenosis 50% and above, the WSSavg, WSSmax and OSI calculated using turbulence model deviates from laminar by more than 10% and the flow disturbances seems to significantly increase only after 70% stenosis. Our model shows reliability and completely validated. CONCLUSIONS: Blood flow through stenosed coronary arteries seems to be turbulent in nature for area stenosis above 70% and the transition to turbulent flow begins from 50% stenosis. PMID- 27280085 TI - Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis. AB - BACKGROUND: Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. METHODS: In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. RESULTS: Predefined renal function improvement (increase in eGFR >=10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48-0.70), 0.71 (95% CI, 0.61-0.81), 0.52 (95% CI, 0.41-0.65), and 0.56 (95% CI, 0.44-0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m(2), similar findings were obtained. CONCLUSIONS: Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function. PMID- 27280086 TI - Utility of brain natriuretic peptide assay as a predictor of short term outcomes in patients presenting with syncope to the emergency department. AB - BACKGROUND: Syncope is a common condition that accounts for 3% of emergency department (ED) visits and 1-6% of hospital admissions. Current admissions practices result in marginal diagnostic and therapeutic benefit and consume healthcare resources. METHODS: This prospective cohort study examined the use of brain natriuretic peptide (BNP) test as a predictor of short term serious outcome in 159 patients who presented to ED with syncope between August 2012 and August 2013 in two tertiary teaching medical centers. RESULTS: A total of 41 patients (36%) had serious outcomes within 1 month, 21 of them were in the low BNP group and 20 were in the high BNP group. There was a significantly higher incidence of serious outcomes, myocardial infarction (MI), and life-threatening arrhythmias in the high BNP group. Patients with BNP >250 has an 8.844 fold increase risk of serious outcomes [odds ratio (OR) 8.844, 95% CI: (3.281 to 23.8), P<0.001], a 14.8-fold increase risk of MI [OR =14.8, 95% CI: (1.57 to 139), P=0.011], and a 4.46-fold increase risk life threatening arrhythmia [OR =4.46, 95% CI: (1.15 18.8), P=0.034]. However, there was no statistically significant difference between the two groups in one month mortality, major bleeding, major cardiac procedures or stroke. CONCLUSIONS: Our study results further validates the ROSE rule and the utility of BNP in risk stratification of syncope patients. This study showed that measuring BNP and adding ROSE rule to the standard evaluation of syncope can sufficiently predict short-term serious outcomes for patients presenting to ED with syncope. PMID- 27280087 TI - Transcatheter versus surgical aortic valve replacement in intermediate risk patients: a meta-analysis. AB - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been approved in patients with high or prohibited surgical risk for surgery for treatment of severe symptomatic aortic stenosis. Prospective studies examining the benefits of TAVR in intermediate risk patients are ongoing. Other smaller studies including lower risk patients have been conducted, but further meta-analysis of these studies is required to draw more broad comparisons. METHODS: A Medline search was conducted using standard methodology to search for clinical trials and observational studies including intermediate risk patients. We limited our meta analysis to studies matching patient populations by propensity scores or randomization and examined clinical outcomes between TAVR and surgical aortic valve replacement (SAVR). RESULTS: Analysis of the TAVR and SAVR cohorts revealed no significant differences in the outcomes of 30-day [OR (95% CI): 0.85 (0.57, 1.26)] or 1-year mortality [OR (95% CI): 0.96 (0.75, 1.23)]. A trend towards benefit with TAVR was noted in terms of neurological events and myocardial infarction (MI) without statistical significance. A statistically significant decrease in risk of post-procedural acute renal failure in the TAVR group [OR (95% CI): 0.52 (0.27, 0.99)] was observed, but so was a significantly higher rate of pacemaker implantations for the TAVR group [OR (95% CI): 6.51 (3.23, 13.12)]. CONCLUSIONS: We conclude that in intermediate risk patients undergoing aortic valve replacement, the risk of mortality, neurological outcomes, and MI do not appear to be significantly different between TAVR and SAVR. However, there appears to be a significant reduction in risk of acute renal failure at the expense of an increased risk of requiring a permanent pacemaker in low and intermediate risk patients undergoing TAVR compared to SAVR. PMID- 27280089 TI - Implications and limitations of the PREPIC2 study-the interventionist's perspective. PMID- 27280090 TI - Conus artery occlusion causing isolated right ventricular outflow tract infarction: novel application of cardiac magnetic resonance in anterior STEMI. AB - Acute ST elevation in the anterior precordial leads typically suggests an anteroseptal infarction due to left anterior descending coronary artery obstruction, but the differential can be broad. Conus branch artery occlusion is a potentially overlooked cause of anteroseptal ST elevation myocardial infraction. Cardiac magnetic resonance (CMR) imaging is an emerging technology which can differentiate the etiology of anterior ST elevation in patients with no apparent coronary abnormalities on coronary angiography and normal echocardiography. PMID- 27280088 TI - Progression of coronary artery calcification at the crossroads: sign of progression or stabilization of coronary atherosclerosis? AB - Coronary artery calcification (CAC) has been strongly established as an independent predictor of adverse events, with a significant incremental prognostic value over traditional risk stratification algorithms. CAC progression has been associated with a higher rate of events. In parallel, several randomized studies and meta-analysis have shown the effectiveness of statins to slow progression and even promote plaque regression. However, evidence regarding the effect of routine medical therapy on CAC has yielded conflicting results, with initial studies showing significant CAC regression, and contemporaneous data showing rather the opposite. Accordingly, there is currently a great controversy on whether progression of CAC is a sign of progression or stabilization of coronary artery disease (CAD). The finding of inexorable CAC progression despite the implementation of intensive contemporaneous medical therapy suggests that further understanding of this phenomenon should be undertaken before the implementation of CAC as a surrogate endpoint for longitudinal studies, or for prospective follow-up of patients under routine medical treatment. PMID- 27280091 TI - Emergent percutaneous coronary intervention for acute myocardial infarction in patients with mirror dextrocardia: case reports and brief review. AB - Mirror-image dextrocardia is a rare congenital abnormality with a life expectancy and risk of myocardial infarction similar to the normal population. Although there have been few case reports of emergent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in mirror-image dextrocardia, physicians, especially general and interventional cardiologists encounter problems in the diagnosis and treatment of AMI in these patients. In this paper, we report our experience with two cases of emergent transradial PCI for AMI in patients with the mirror-image dextrocardia. Subsequently, we summarize clinical features, electrocardiograph characteristic, approach to emergent PCI based on a review of the literature. PMID- 27280092 TI - Ruptured aneurysm of major aortopulmonary collateral artery: management using amplatzer vascular plug. AB - Aneurysm of a major aortopulmonary collateral artery (MAPCA) is quite rare. Aneurysmally dilated MAPCA may be complicated with rupture and massive hemoptysis leading to sudden death. Possible pathophysiology for aneurysm formation is persistent high pressure state in collateral circulation. High index of suspicion is necessary to avoid catastrophic complications as the amount of hemoptysis does not correlate with disease severity and etiology. We present a case of large ruptured aneurysm of a MAPCA presenting with massive haemoptysis in a patient of cyanotic congenital heart disease which was salvaged by endovascular deployment of vascular plug. PMID- 27280093 TI - Prof. Koffi Herve Yangni-Angate: open heart surgery in Africa. PMID- 27280094 TI - Comparison of Titanium vs. Polycel Total Ossicular Replacement Prosthesis. AB - INTRODUCTION: Even though modern technology progresses so rapidly, annals of otology are replete with so many challenging article, which often compare various types of prosthesis. Since there has not been a prospective randomized clinical trial study which compares the hearing result of total ossicular replacement prosthesis made of Titanium with omega connector and Polycel in the literature, we decided to perform a study encompassing this issue. MATERIALS AND METHODS: 105 patients, who were in the 2nd stage of their operation and who needed total ossicular replacement prosthesis, were included in this prospective single blind randomized clinical trial study. Patients were classified in two groups: titanium Kurz (TTPTM -Vario system, Kurz GmbH, Dusslingen, Germany) with omega connector and Polycel (Sheehy Plastipore Polycel, Medtronic Xomed Inc). The duration of the follow up was 6-12 months. In order to evaluate hearing results, pure tone audiometric in 0.5, 1, 2, and 4 kHz were checked. In addition, speech reception threshold was recorded. A successful surgery was defined as having a postoperative air-bone gap within 20 dB. RESULTS: We accomplished successful hearing in 64.4% of patients with titanium and 65% of patients with a Polycel prosthesis.Improvement in speech reception threshold was 11.5 dB in the titanium group and 13 dB in the Polycel group. In other words, there was no significant difference between the two groups. In addition, air-bone gap improvement after ossiculoplasty was 11.2 dB in the patients with a titanium prosthesis and 12.4 dB in the Polycel group. In fact, the difference was not significant. CONCLUSION: We found that both the titanium and the Polycel prosthesis improve speech reception threshold and air-bone gap closure in a similar manner. PMID- 27280095 TI - Evaluation of Factors Affecting the Surgical Outcome in Tympanoplasty. AB - INTRODUCTION: Tympanoplasty is a standard procedure to repair tympanic membrane perforation. The aim of this study is to evaluate the results of tympanoplasty (hearing improvement and tympanic membrane closure rate) in patients suffering from chronic perforation of the tympanic membrane by considering the prognostic factors. MATERIALS AND METHODS: In a prospective study, based on the results of tympanoplasty with temporal graft fascia in 60 patients in the ENT department of the Medical Science University of Tabriz, we evaluated prognostic factors, such as age, sex, smoking, size, and site of perforation, for the outcome of this surgery. RESULTS: The rate of surgical success- integration of the graft- was 93.3%. Improvement of hearing, as demonstrated through audiometry, occurred in 93% of cases. We did not find any factors to be statistically significant to affect surgical outcome. CONCLUSION: Even by considering the influence of different factors on the results of a tympanoplasty operation, according to the statistical results of this study, there is not a significant difference in the results of the operation, neither in the health of the tympanic membrane after surgery nor in hearing development. PMID- 27280096 TI - Frequency of Congenital Heart Diseases in Prelingual Sensory-Neural Deaf Children. AB - INTRODUCTION: Hearing impairment is the most frequent sensorial congenital defect in newborns and has increased to 2-4 cases per 1,000 live births. Sensory-neural hearing loss (SNHL) accounts for more than 90% of all hearing loss. This disorder is associated with other congenital disorders such as renal, skeletal, ocular, and cardiac disorders. Given that congenital heart diseases are life-threatening, we decided to study the frequency of congenital heart diseases in children with congenital sensory-neural deafness. MATERIALS AND METHODS: All children who had undergone cochlear implantation surgery due to SNHL and who had attended our hospital for speech therapy during 2008-2011 were evaluated by Doppler echocardiography. RESULTS: Thirty-one children (15 boys and 16 girls) with a mean age of 55.70 months were examined, and underwent electrocardiography (ECG) and echocardiography. None of the children had any signs of heart problems in their medical records. Most of their heart examinations were normal, one patient had expiratory wheeze, four (12%) had mid-systolic click, and four (12%) had an intensified S1 sound. In echocardiography, 15 children (46%) had mitral valve prolapse (MVP) and two (6%) had minimal mitral regurgitation (MR). Mean ejection fraction (EF) was 69% and the mean fractional shortening (FS) was 38%. CONCLUSION: This study indicates the need for echocardiography and heart examinations in children with SNHL. PMID- 27280097 TI - Development and Validation of a Persian Version of Dichotic Emotional Word Test. AB - INTRODUCTION: Emotional words in comparison with neutral words have different hemispheric specialization. It is assumed that the right hemisphere has a role in processing every kind of emotional word. The objective of the present study was the development of a Persian version of the dichotic emotional word test and evaluate its validation among adult Persian speakers. MATERIALS AND METHODS: The present study was done on 60 adults, with the age ranging from 18-30 years for both genders, who had no history of neurological disorders with normal hearing. The developed test included eight main lists; each had several dichotic emotional/ neutral pairs of words. Participants were asked to recall as many words in each list as they could after they listened to them. A content validity index was used to analyze the validity of the test. RESULTS: The mean content validity index score was 0.94. The findings showed that in the left ear, emotional words were remembered more than neutral ones (P=0.007). While in the right ear, neutral words were remembered more (P=0.009). There were no significant differences in male and female scores. CONCLUSION: Dichotic emotional word test has a high content validity. The ability to remember emotional words better in the left ear supports the dominant role of the right hemisphere in emotional word perception. PMID- 27280098 TI - Integrated Internal Stabilization for Saddle Nose Surgery. AB - INTRODUCTION: Correction of Saddle nose deformity is one of the most challenging issues in facial plastic surgery. MATERIALS AND METHODS: In this study, a single structure in the form of L-strut was attempted to be created by using one 0.035" Kirschner wire and an autologous costal graft out of the 10th and 11th ribs. This study involved 13 cases, most of whom were traumatic. The corrective surgical techniques used in this study will be described in detail. RESULTS: There was no warping, no rejection, and no infection in the created L-strut and patients' satisfaction was very good during the follow up period. CONCLUSION: Surgical correction of a saddle-shaped nose using the described technique seems to be an acceptable and uncomplicated technique, and the cosmetic result is totally acceptable. PMID- 27280100 TI - Prevalence of Associated Anomalies in Cleft Lip and/or Palate Patients. AB - INTRODUCTION: Orofacial clefts are among the most common congenital anomalies. Patients presenting with orofacial clefts often require surgery or other complex procedures. A cleft lip or palate can be a single anomaly or a part of multiple congenital anomalies. The reported prevalence of cleft disease and associated anomalies varies widely across the literature, and is dependent on the diagnostic procedure used. In this study we determined the prevalence of associated anomalies in patients with a cleft lip and/or palate, with a specific focus on cardiac anomalies. MATERIALS AND METHODS: In this cross-sectional study, 526 patients with a cleft lip and /or palate admitted to the children's referral hospital between 2006 and 2011 were evaluated. All associated anomalies were detected and recorded. Patient information collected included age, gender, type and side of cleft, craniofacial anomalies and presence of other anomalies, including cardiac anomalies. Data were analyzed using SPSS version 16. RESULTS: Of the 526 patients enrolled in the study, 58% (305) were male and 42% (221) were female. In total, 75% of patients (396) were aged between 4 and 8 years and 25% (130) were aged less than 4 years. The most common cleft type in our study was bilateral cleft palate. The most commonly associated anomaly among cleft patients, in 12% of cleft patients, was a cardiac anomaly. The most common cardiac anomaly was atrial septal defect (ASD). CONCLUSION: The prevalence of associated anomalies among orofacial cleft patients is high. The most common associated anomaly is cardiac anomaly, with ASD being the most common cardiac anomaly. There are no significant relationships between type of cleft and associated cardiac anomalies. PMID- 27280099 TI - Smell Decline as a good Predictor of Sinonasal Polyposis Recurrence after Endoscopic Surgery. AB - INTRODUCTION: To evaluate the most sensitive symptom to predict early recurrence of nasal polyposis. Prospective longitudinal cohort study. Tertiary university referral center with accredited otorhinolaryngology residency programs. MATERIALS AND METHODS: In this prospective study, we evaluated 62 patients with diffuse nasal polyposis. All patients underwent functional endoscopic sinus surgery. The author-devised questionnaire relating to the four major symptoms of chronic rhinosinusitis were answered by patients at the pre-operative visit and at 1, 3, 6, 12, and 24 months after surgery. Patients were followed up with serial endoscopic examinations, and a computed tomography (CT) scan was performed if indicated. RESULTS: All 62 patients (37 male, 25 female) completed the study. The mean age was 41.24 +/- 12.47 years. All major symptoms showed significant improvement after surgery (P=0.000); however, the severity of symptoms gradually increased in patients with a recurrence of polyposis, but at different points in time (P= 0.008). Sense of smell was the first symptom to deteriorate in patients with relapse (mean, 6 months) followed by nasal secretion (12 months), obstruction and pain(24 months). Patients with asthma, Samter's triad, allergic fungal rhinosinusitis (AFRS) and allergic rhinitis showed symptoms of recurrence sooner than other patients (P<0.05). CONCLUSION: The most sensitive symptom for the early detection of recurrence of nasal polyposis is a decrease in the sense of smell. Nasal obstruction and facial pain were observed in the late stage of relapse when frank polyposis formation was established. PMID- 27280101 TI - Evaluation of Post Laryngectomy Pharyngocutaneous Fistula risk Factors. AB - INTRODUCTION: Pharyngocutaneous fistula (PCF) is the most common complication after total laryngectomy. Its incidence is extremely variable, with values ranging from 3% and 65%. The management of this problem considerably increases the length and the cost of hospitalization. The aim of this study is to analyze the incidence, predisposing factors, and outcome of PCF in patients undergoing total laryngectomy in a Moroccan teaching hospital in Rabat, Morocco. MATERIALS AND METHODS: This study is a retrospective study including 136 patients who underwent total laryngectomy for squamous cell carcinoma of the larynx in our institution, between January 2006 and December 2013. Socio-demographical, biological, surgical, and outcome data were included. Risk factors were analyzed for association with PCF formation. RESULTS: The overall PCF rate was 27.8%. The mean age was 58 (32-82 years). Univariate analysis showed age (P= 0,028), hemoglobin (P=0,026), and previous tracheotomy (P=0,028) to be associated with the onset of PCF. However, multivariate analysis revealed that previous tracheotomy (P=0,028) and low level of preoperative hemoglobin (P=0,026) were highly associated with the occurrence of PCF. CONCLUSION: This is an original work performed in an African country with a large serie. Our findings suggest that age, previous tracheotomy, and low level of haemoglobin are risk factors for PCF onset after total laryngectomy in T4 squamous cell carcinoma. PMID- 27280102 TI - A Case of Undiagnosed Sleep Disorder with Hearing Difficulty and Dizziness. AB - INTRODUCTION: The aim of this case report was to investigate the relationship between sleep disorders and audio vestibular symptoms. CASE REPORT: A case of undiagnosed sleep disorder, presenting as a temporary auditory processing difficulty, is presented. The disorder was initially treated as sudden deafness with dizziness. A 23-year-old male patient complained of acute hearing disturbance despite normal results on pure tone audiometry. The patient was initially administered a steroid injection in the hospital. After treatment, his hearing symptoms improved only slightly and he reported balance difficulty with rightward spontaneous nystagmus. Vestibular rehabilitation was performed. We also suspected that his hearing symptom was due to an auditory processing difficulty. Despite steroid treatment and vestibular rehabilitation, neither of his symptoms improved. We subsequently identified the presence of insomnia. He was prescribed zolpidem 5 mg, which slightly improved his symptoms, and referred to a sleep specialist for further examination. Polysomnography was performed, which identified restless leg syndrome and sleep disturbance with delayed sleep phase syndrome. After pharmacological treatment, his sleep disturbance, hearing difficulty, and balance disorder completely resolved. CONCLUSION: Sleep disorders may provoke reversible auditory processing difficulties. We should carefully evaluate patients for a potentially undiagnosed sleep disorder, even in patients chiefly complaining of intractable sensory dysfunction such as hearing or balance disturbance. PMID- 27280103 TI - Congenital Pleomorphic Adenoma in a SubmandibularGland of a Newborn- A Case Report. AB - INTRODUCTION: Pleomorphic adenoma is a rare benign salivary gland neoplasm in children, which can be treated by simple excision. This tumor is rarely included in the differential diagnosis of solid submandibular masses in children. In the neonates, congenital pleomorphic adenoma usually presents in the nasopharynx. Surgical excision is the treatment of choice and recurrence is not expected. We report what appears to be the first case of congenital pleomorphic adenoma in the submandibular region in a one-day-old newborn. CASE REPORT: The case of a one-day old term baby is presented with a 5x2 cm left submandibualr mass with extension to the oral cavity. The mass was hard and non-mobile. During Ultrasonography and Contrast-enhanced Computed Tomography (CT) scan, the mass was solid with a heterogeneous internal structure. The tumor was completely excised and proved to be a pleomorphic adenoma during histopathological examination. CONCLUSION: Congenital pleomorphic adenoma rarely occurs in the nasopharynx and is treated by surgical excision. Our case is unique because the congenital pleomorphic adenoma is located in the submandibular gland of a newborn. PMID- 27280104 TI - Autologous Cricoid Cartilage as a Graft for Airway Reconstruction in an Emergent Technique - A Case Report. AB - INTRODUCTION: Laryngotracheal stenosis can be caused after traumatic injuries to the neck from the subglottic larynx to the trachea. Patients with laryngotracheal stenosis often need a tracheotomy and occasionally may become tracheotomy dependent. Different procedures have been described for the management of these lesions. Management options include techniques of endoscopic dilation, laser resection, laryngo-fissure, and an innovative array of plastic reconstructions with or without the use of stents. CASE REPORT: This paper presents airway reconstruction in a young patient with severe subglottic stenosis due to a blunt trauma to the neck, who was treated using particles of an autologous fractured cricoid cartilage as the source for airway augmentation. An incision was made in the anterior midline of the cricoid lamina and deepened through the scar tissue to the posterior cricoid lamina. Then two lateral incisions (right & left) were made in the cricoid lamina and fractured cartilage particles and the scar tissue were removed via these two lateral incisions. The mucosal lining at the right and left of the midline incision, after debulking, were sutured to a lateral position. Thereafter three cartilage particles were used to reconstruct the anterior cricoid lamina and augment the lumen. CONCLUSION: It is worth to mention that an autologus cartilage graft can be used for certain cases with traumatic airway stenosis. Further follow up and more patients are needed to approve this method of reconstructive surgery in emergent situations. PMID- 27280105 TI - Ortner's Syndrome-A Rare Cause of Hoarseness: Its Importance to an Otorhinolaryngologist. AB - INTRODUCTION: Cardiovocal hoarseness (Ortner's syndrome) is hoarseness of voice due to recurrent laryngeal nerve involvement secondary to cardiovascular disease. Recurrent laryngeal nerve in its course (especially the left side) follows a path that brings it in close proximity to numerous structures. These structures interfere with its function by pressure or by disruption of the nerve caused by disease invading the nerve. However painless asymptomatic intramural hematoma of the aortic arch, causing hoarseness as the only symptom, is a rare presentation as in this case. CASE REPORT: We report a case of silent aortic intramural hematoma which manifested as hoarseness as the only presenting symptom. A detailed history and thorough clinical examination could not reveal the pathology of hoarseness. The cause of hoarseness was diagnosed as aortic intramural hematoma on contrast computed tomography. Thus the patient was diagnosed as case of cardiovocal hoarseness (Ortner's syndrome) secondary to aortic intramural hematoma. CONCLUSION: A silent aortic intramural hematoma with hoarseness as the only presenting symptom is very rare. This particular case report holds lot of significance to an otolaryngologist as he should be aware of this entity and should always consider it in the differential diagnosis of hoarseness. PMID- 27280106 TI - Management of Large Tongue Schwannoma - A Short Report. PMID- 27280107 TI - Clinical Challenges to Current Molecularly Targeted Therapies in Lung Cancer. AB - Lung cancer is difficult to treat with a poor prognosis and a five year survival of 15%. Current molecularly targeted therapies are initially effective in non small cell lung cancer (NSCLC) patients; however, they are plagued with difficulties including induced resistance and small therapeutically responsive populations. This mini review describes the mechanism of resistance to several molecularly targeted therapies which are currently being used to treat NSCLC. The major targets discussed are c-Met, EGFR, HER2, ALK, VEGFR, and BRAF. The first generation tyrosine kinase inhibitors (TKIs) resulted in resistance; however, second and third generation TKIs are being developed, which are generally more efficacious and have potential to treat NSCLC patients with resistance to first generation TKIs. Combination therapies could also be effective in preventing TKI resistance in NSCLC patients. PMID- 27280108 TI - Anticoagulation and population risk of stroke and death in incident atrial fibrillation: a population-based cohort study. AB - BACKGROUND: Atrial fibrillation increases the risk of stroke and death. Anticoagulation therapy is an effective treatment for stroke prevention, but remains underused in the community. We sought to determine the effectiveness and safety of anticoagulation therapy in an inception cohort with new-onset atrial fibrillation in the province of Alberta, Canada. METHODS: We conducted a population-based cohort study of atrial fibrillation using an administrative database from Alberta's publicly funded and universally available health care system. All new-onset atrial fibrillation patients from Jan. 1, 2009, to Dec. 31, 2010, were included in the cohort and followed through Dec. 31, 2013. We assessed anticoagulation status as a predictor of stroke and death using time-to-event analysis and adjusted for sex and CHADS2 (congestive heart failure, hypertension, age >= 75 yr, diabetes mellitus and prior stroke or transient ischemic attack) score using Cox proportional hazards modelling. RESULTS: We identified 10 745 patients, 7358 (68.5%) of whom received anticoagulation therapy, principally with warfarin (n = 6997, 95.1%). Anticoagulation therapy was associated with significantly decreased risk of ischemic stroke (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), all stroke (HR 0.77, 95% CI 0.65-0.91), all stroke and death (HR 0.70, 95% CI 0.62-0.72) and all-cause mortality (HR 0.67, 95% CI 0.62-0.72), despite an association with increased risk of hemorrhagic stroke (HR 1.92, 95% CI 1.17-3.16). There was a neutral association with subdural (HR 1.01, 95% CI 0.53-1.93) and gastrointestinal (HR 0.96, 95% CI 0.70-1.31) hemorrhage. INTERPRETATION: Anticoagulation therapy is effective and safe for stroke prevention and decreases mortality in patients with incident atrial fibrillation. These population data support an aggressive approach to screening for atrial fibrillation and treatment with anticoagulant medicines to prevent stroke and death. PMID- 27280109 TI - Breastfeeding difficulties and supports and risk of postpartum depression in a cohort of womenwho have given birth in Calgary: a prospective cohort study. AB - BACKGROUND: A link exists between breastfeeding difficulties and postpartum depression, and evidence shows that some breastfeeding promotion initiatives may increase maternal stress and contribute to risk of the condition. We conducted a prospective cohort study to determine whether breastfeeding difficulties affect the risk of postpartum depression and whether breastfeeding support modifies the relationship between breastfeeding difficulties and postpartum depression. METHODS: Between June and October 2010, we recruited 442 women who intended to breastfeed from all maternity hospitals in Calgary within 72 hours of giving birth to full-term, singleton infants. We administered questionnaires at birth and 6 weeks and 6 months postpartum, measuring breastfeeding difficulties, exposure to breastfeeding supports and postpartum depression. We used qualitative inquiry to measure breastfeeding support experiences. Postpartum depression was defined as a score of 10 or greater on the Edinburgh Postnatal Depression Scale or a self-reported diagnosis of depression in the first 6 months postpartum. RESULTS: A total of 386 women (87.3%) reported moderate to severe breastfeeding difficulties and 437 (98.9%) received some form of breastfeeding advice, help or support. Among women with breastfeeding difficulties, those who did not report a negative breastfeeding support experience were at decreased risk of postpartum depression (risk ratio 0.36). In the final regression model a negative breastfeeding support experience was a significant effect modifier of the relationship between breastfeeding difficulties and postpartum depression. INTERPRETATION: The quality of breastfeeding support is important not only for breastfeeding promotion but also for maternal mental health. Educating front-line caregivers to ensure that support experiences of breastfeeding women are positive can reduce the risk of postpartum depression. PMID- 27280110 TI - Sex differences in the outcomes of peripheral arterial disease: a population based cohort study. AB - BACKGROUND: The role of sex in the outcomes of patients with peripheral arterial disease (PAD) has been poorly studied. We sought to investigate differences in the long-term adverse cardiovascular and limb outcomes between men and women with PAD. METHODS: We conducted a population-based cohort study with up to 7 years of follow-up using linked administrative databases in Ontario, Canada. Patients aged 40 years or older who visited a vascular surgeon between Apr. 1, 2004, and Mar. 31, 2007 (index date), and carried a diagnosis of PAD comprised the study cohort. The primary outcome was a composite of death or hospital admission for stroke or myocardial infarction. Secondary outcomes included lower limb amputation or revascularization. We used Cox proportional hazards modelling to compute unadjusted hazard ratios (HRs) and HRs adjusted for baseline covariates. RESULTS: A total of 6915 patients were studied, of whom 2461 (35.6%) were women. No significant differences in the risk of the primary outcome were observed between men and women (adjusted HR 0.99 [95% confidence interval (CI) 0.92-1.05]). Women were less likely than men to undergo minor amputation (adjusted HR 0.73 [95% CI 0.62-0.85]) and arterial bypass surgery (adjusted HR 0.82 [95% CI 0.71-0.94]) but were more likely to be admitted to hospital for acute myocardial infarction (adjusted HR 1.15 [95% CI 1.00-1.31]). There were no sex differences in the rates of major amputation or transluminal percutaneous angioplasty. INTERPRETATION: We identified no significant differences in the composite risk of major adverse cardiovascular events between women and men with PAD, although our findings suggest men may be at increased risk for adverse limb events compared with women. Cardiovascular health campaigns should focus on both women and men to promote early diagnosis and management of PAD. PMID- 27280111 TI - Postpartum domperidone use in British Columbia: a retrospective cohort study. AB - BACKGROUND: Domperidone is commonly used off-label to stimulate milk production in mothers who have low milk supply. The aim of this study was to describe trends, patterns and determinants of postpartum domperidone use. METHODS: This is a retrospective, population-based study involving all women with a live birth between Jan. 1, 2002, and Dec. 31, 2011, in the province of British Columbia. We examined administrative data sets containing person-specific information on filled prescriptions and use of medical services, and we used logistic regression to examine associations between domperidone use and maternal characteristics. RESULTS: The study population consisted of 225 532 women with 320 351 live births. The prevalence of postpartum domperidone use more than doubled between 2002 and 2011. In 2011, 1 in 3 women with a preterm birth and 1 in 5 women with a full-term birth were prescribed domperidone in the first 6 months postpartum. Women who were older, had a higher body mass index, had a chronic disease, were first-time mothers, delivered more than 1 baby (multiple pregnancy), had a preterm birth or had a cesarian delivery were more likely to fill a postpartum domperidone prescription. INTERPRETATION: We found an increase in postpartum domperidone use over a 10-year period. More research is needed on maternal and infant health outcomes. PMID- 27280112 TI - Temporal trends in ankyloglossia and frenotomy in British Columbia, Canada, 2004 2013: a population-based study. AB - BACKGROUND: Routine surveillance of congenital anomalies has shown recent increases in ankyloglossia (tongue-tie) in British Columbia, Canada. We examined the temporal trends in ankyloglossia and its surgical treatment (frenotomy). METHODS: We conducted a population-based cohort study involving all live births in British Columbia from Apr. 1, 2004, to Mar. 31, 2014, with data obtained from the province's Perinatal Data Registry. Spatiotemporal trends in ankyloglossia and frenotomy, and associations with maternal and infant characteristics, were quantified using logistic regression analysis. RESULTS: There were 459 445 live births and 3022 cases of ankyloglossia between 2004 and 2013. The population incidence of ankyloglossia increased by 70% (rate ratio 1.70, 95% confidence interval [CI] 1.44-2.01), from 5.0 per 1000 live births in 2004 to 8.4 per 1000 in 2013. During the same period, the population rate of frenotomy increased by 89% (95% CI 52%-134%), from 2.8 per 1000 live births in 2004 to 5.3 per 1000 in 2013. The 2 regional health authorities with the lowest population rates of frenotomy (1.5 and 1.8 per 1000 live births) had the lowest rates of ankyloglossia and the lowest rates of frenotomy among cases with ankyloglossia, whereas the 2 regional health authorities with the highest population rates of frenotomy (5.2 and 5.3 per 1000 live births) had high rates of ankyloglossia and the highest rates of frenotomy among cases of ankyloglossia. Nulliparity, multiple birth, male infant sex, birth weight and year were independently associated with ankyloglossia. INTERPRETATION: Large temporal increases and substantial spatial variations in ankyloglossia and frenotomy rates were observed that may indicate a diagnostic suspicion bias and increasing use of a potentially unnecessary surgical procedure among infants. PMID- 27280113 TI - Profile of tobacco users identified in primary care practice and predictors of readiness to quit: a cross-sectional survey. AB - BACKGROUND: The aim of this study was to document the prevalence of tobacco use and describe the characteristics of tobacco users identified in primary care practices. METHODS: We conducted a cross-sectional survey in 49 primary care practices in the province of Ontario. Consecutive patients were screened for smoking status at the time of their clinic appointment. Patients reporting current tobacco use completed a survey, which documented sociodemographic and smoking-related characteristics. Multilevel modelling was used to examine predictors of readiness to quit smoking and the presence of anxiety and/or depression. RESULTS: A total of 56 592 patients were screened, and 5245 tobacco users participated in the survey. Prevalence of tobacco use was 18.2% and varied significantly across practices (range 12.4%-36.1%). Of the respondents, 46.3% reported current anxiety and/or depression, and 61.3% reported smoking within the first 30 minutes of waking. A total of 41.1% of respondents reported they were ready to quit smoking in the next 6 months, and 30.1% reported readiness to quit in the next 30 days. Readiness to quit was positively associated with higher self efficacy, male sex, presence of chronic obstructive pulmonary disease and more years of tobacco use. The presence of anxiety and/or depression was associated with lower cessation self-efficacy and time to first cigarette within 30 minutes of waking, but did not predict readiness to quit. INTERPRETATION: Tobacco users identified in primary care practices reported high rates of nicotine dependence and anxiety and/or depression, but also high rates of readiness to quit. Study findings support the need to tailor interventions to address the needs of tobacco users identified in primary care settings. PMID- 27280114 TI - Assessment of the effect of cold and hot temperatures on mortality in Ontario, Canada: a population-based study. AB - BACKGROUND: Ambient high temperature is associated with death; however, heat related risk of death has not been quantified systematically in Ontario, the most populous province in Canada. Less is known about cold-related risk in this population. Our objective was to quantify the health impact from cold and hot temperatures in Ontario. METHODS: The study population consisted of all residents of Ontario who died between Jan. 1, 1996, and Dec. 31, 2010, from any nonaccidental cause. A case-crossover analysis was applied to assess the relation between daily temperature fluctuation and deaths from nonaccidental and selected causes in cold (December-February) and warm (June-August) seasons, respectively, adjusting for various potential confounders. Risk estimates were obtained for each census division, then pooled across Ontario. We examined potential effect modification for selected comorbidities and sociodemographic characteristics. RESULTS: In warm seasons, each 5 degrees C increase in daily mean temperature was associated with a 2.5% increase in nonaccidental deaths (95% confidence interval [CI] = 1.3% to 3.8%) on the day of exposure (lag 0). In cold seasons, each 5 degrees C decrease in daily temperature was associated with a 3.0% (95% CI 1.8% to 4.2%) increase in nonaccidental deaths, which persisted over 7 days (lag 0-6). The cold-related effects (lag 0-6) were stronger for cardiovascular-related deaths (any cardiovascular death: 4.1%, 95% CI 2.3% to 5.9%; ischemic heart disease: 5.8%, 95% CI 3.6% to 8.1%), especially among people less than 65 years of age (8.0%, 95% CI 3.0% to 13.0%). Conversely, heat most strongly increased respiratory-related deaths during admission to hospital (26.0%, 95% CI 0% to 61.4%). Across Ontario, each 5 degrees C change in daily temperature was estimated to induce 7 excess deaths per day in cold seasons and 4 excess deaths in warm seasons. INTERPRETATION: Heat contributed to excess deaths in Ontario, although the effect of cold weather appeared to be greater. Further work is required to better define high-risk subgroups, which might include the homeless and people with inadequately heated housing. PMID- 27280115 TI - Impact of Canadian tobacco packaging policy on use of a toll-free quit-smoking line: an interrupted time-series analysis. AB - BACKGROUND: A policy for new pictorial health warning labels on tobacco packaging was introduced by Health Canada in 2012. The labels included, for the first time, a prominently displayed toll-free number for a quit-smoking line. We used data from the Ontario provincial quitline to investigate the call volume and number of new callers receiving treatment in the months before and after the new policy was introduced. METHODS: We used an interrupted time-series analysis to examine trends in the overall call volume and number of new callers receiving treatment (>= 1 telephone counselling session) through Ontario's quitline (Smokers' Helpline) between January 2010 and December 2013. We analyzed data using Box Jenkins autoregressive integrated moving-average models; we adjusted the models for a major campaign promoting the quitline, a seasonality (January) effect and tobacco pricing. RESULTS: We found a relative increase of 160% in the average monthly call volume during the 7 months after the introduction of the new labels (870 calls per month at baseline and 1391 additional calls per month on average after the policy change; standard error [SE] 108.94, p < 0.001), and a sustained increase of 43% in subsequent months. We observed a relative increase of 174% in the number of new callers receiving treatment (153 new callers per month at baseline and 267 additional new callers per month after the policy change; SE 40.03, p < 0.001) and a sustained increase of 80% in subsequent months. The effect was significant even after controlling for a major promotion campaign and the January effect. INTERPRETATION: We found a significant increase in the monthly overall call volume and number of new callers receiving treatment per month after the introduction of the new tobacco health warning labels, with a sustained increase in overall calls and new callers beyond the first 7 months. Our findings add to the body of evidence on the benefit of including a toll-free quitline number on tobacco packaging. PMID- 27280116 TI - Association of hospital and physician case volumes with cardiac monitoring and cardiotoxicity during adjuvant trastuzumab treatment for breast cancer: a retrospective cohort study. AB - BACKGROUND: Adjuvant trastuzumab is the standard of care for patients with HER2 overexpressing breast cancer, but use of trastuzumab may lead to cardiotoxicity. Our goal was to evaluate the relationship between hospital and physician case volume and cardiac outcomes in this population. METHODS: In this retrospective cohort study, we identified all female patients in Ontario with a breast cancer diagnosis in 2003-2009 who underwent treatment with trastuzumab through a provincial drug-funding program and linked these patients to administrative databases to ascertain patient demographics, treating hospital and physician characteristics, admissions to hospital, cardiac risk factors, cardiac imaging and comorbidities. Insufficient cardiac monitoring was defined as per the Canadian Trastuzumab Working Group guideline. Cardiotoxicity was defined as receiving fewer than 16 of 18 doses of trastuzumab because of heart failure admission, heart failure diagnosis or discontinuation of the drug after cardiac imaging. We constructed hierarchical multivariable logistic regression models to evaluate the effect of annual hospital volume, cumulative physician volume and treatment period on cardiac monitoring and cardiotoxicity. RESULTS: Of 3777 women treated by 214 oncologists at 68 hospitals, 918 (24.3%) had insufficient cardiac monitoring and cardiotoxicity developed in 640 (16.9%). Cardiotoxicity occurred in 389 (42.4%) and 251 (8.8%) patients in the insufficient- and sufficient monitoring groups, respectively. Higher annual hospital and cumulative physician volumes, and more recent calendar period, were all independent predictors for decreased cardiotoxicity. Adjustment for rates of cardiac monitoring annulled the relationships between case volume and cardiotoxicity. INTERPRETATION: Greater hospital and physician case volumes are associated with reduced rates of trastuzumab-related cardiotoxicity, most likely because of better cardiac monitoring at higher volume centres. PMID- 27280117 TI - Trends in prostate cancer incidence and mortality in Canada during the era of prostate-specific antigen screening. AB - BACKGROUND: Widespread use of prostate-specific antigen (PSA) to screen for prostate cancer began in the early 1990s. Advocates for screening assert that this has caused a decrease in prostate cancer mortality. We sought to describe secular changes in prostate cancer incidence and mortality in Canada in relation to the onset of PSA screening. METHODS: Age-standardized and age-specific prostate cancer incidence (1969-2007) and mortality (1969-2009) from Public Health Agency of Canada databases were analyzed by joinpoint regression. Changes in incidence and mortality were related to introduction of PSA screening. RESULTS: Prior to PSA screening, prostate cancer incidence increased from 54.2 to 99.8 per 100 000 between 1969 and 1990. Thereafter, incidence increased sharply (12.8% per year) to peak at 140.8/100 000 in 1993. After decreasing in all age groups between 1993 and 1996, incidence continued to increase for men aged less than 70 years, but decreased for older men. Age-standardized mortality was stable from 1969 to 1977, increased 1.4% per year to peak in 1995 and subsequently decreased at 3.3% per year; the decline started from 1987 in younger men (age < 60 yr). INTERPRETATION: Incidence was increasing before PSA screening occurred, but rose further after it was introduced. Reductions in prostate cancer mortality began before PSA screening was widely used and were larger than could be anticipated from screening alone. These findings suggest that screening caused artifactual increase in incidence, but no more than a part of reductions in prostate cancer mortality. The reduction may be due to changing treatment or certification of death. PMID- 27280118 TI - Relation between primary care physician supply and diabetes care and outcomes: a cross-sectional study. AB - BACKGROUND: Higher primary care physician supply is associated with lower mortality due to heart disease, cancer and stroke, but its relation to diabetes care and outcomes is unknown. We examined the association between primary care physician supply and evidence-based testing and hospital visits for people with diabetes in naturally occurring multispecialty physician networks in Ontario, Canada. METHODS: We conducted a cross-sectional analysis between Apr. 1, 2009, and Mar. 31, 2011, using linked administrative data. We included all Ontario residents over 40 years of age with a diagnosis of diabetes before Apr. 1, 2007, who were alive on Apr. 1, 2009 (N = 712 681). We tested the association between physician supply and outcomes at the network level using separate Poisson regression models for urban and nonurban physician networks. We accounted for clustering at the physician and network level and adjusted for patient characteristics. RESULTS: Patients in physician networks with a high supply of primary care physicians were more likely to receive the optimal number of evidence-based tests for diabetes than patients in networks with low primary care physician supply (urban relative risk [RR] 1.06, 95% confidence interval [CI] 1.04-1.07; nonurban RR 1.17, 95% CI 1.14-1.21) but were no different regarding emergency department visits (urban RR 1.05, 95% CI 0.94-1.17; nonurban RR 0.96, 95% CI 0.85-1.08) or hospital admissions for diabetes complications (urban RR 1.01, 95% CI 0.89-1.14; nonurban RR 0.91, 95% CI 0.77-1.07). INTERPRETATION: Having more primary care physicians per capita is associated with better diabetes care but not with reduced hospital visits in this setting. Further research to understand this relation and how it varies by setting is important for resource planning. PMID- 27280119 TI - Performance of residents using digital images versus glass slides on certification examination in anatomical pathology: a mixed methods pilot study. AB - BACKGROUND: It is anticipated that many licensing examination centres for pathology will begin fully digitizing the certification examinations. The objective of our study was to test the feasibility of a fully digital examination and to assess the needs, concerns and expectations of pathology residents in moving from a glass slide-based examination to a fully digital examination. METHODS: We conducted a mixed methods study that compared, after randomization, the performance of senior residents (postgraduate years 4 and 5) in 7 accredited anatomical pathology training programs across Canada on a pathology examination using either glass slides or digital whole-slide scanned images of the slides. The pilot examination was followed by a post-test survey. In addition, pathology residents from all levels of training were invited to participate in an online survey. RESULTS: A total of 100 residents participated in the pilot examination; 49 were given glass slides instead of digital images. We found no significant difference in examination results between the 2 groups of residents (estimated marginal mean 8.23/12, 95% confidence interval [CI] 7.72-8.87, for glass slides; 7.84/12, 95% CI 7.28-8.41, for digital slides). In the post-test survey, most of the respondents expressed concerns with the digital examination, including slowly functioning software, blurring and poor detail of images, particularly nuclear features. All of the respondents of the general survey (n = 179) agreed that additional training was required if the examination were to become fully digital. INTERPRETATION: Although the performance of residents completing pathology examinations with glass slides was comparable to that of residents using digital images, our study showed that residents were not comfortable with the digital technology, especially given their current level of exposure to it. Additional training may be needed before implementing a fully digital examination, with consideration for a gradual transition. PMID- 27280120 TI - Diabetic retinopathy screening with pharmacy-based teleophthalmology in a semiurban setting: a cost-effectiveness analysis. AB - BACKGROUND: Diabetic eye complications are the leading cause of visual loss among working-aged people. Pharmacy-based teleophthalmology has emerged as a possible alternative to in-person examination that may facilitate compliance with evidence based recommendations and reduce barriers to specialized eye care. The objective of this study was to estimate the cost-effectiveness of mobile teleophthalmology screening compared with in-person examination (primary care) for the diabetic population residing in semiurban areas of southwestern Ontario. METHODS: A decision tree was constructed to compare in-person examination (comparator program) versus pharmacy-based teleophthalmology (intervention program). The economic model was designed to identify patients with more than minimal diabetic retinopathy, manifested by at least 1 microaneurysm at examination (modified Airlie House classification grade of >= 20). Cost-effectiveness was assessed as cost per case detected (true-positive result) and cost per case correctly diagnosed (including true-positive and true-negative results). RESULTS: The cost per case detected was $510 with in-person examination and $478 with teleophthalmology, and the cost per case correctly diagnosed was $107 and $102 respectively. The incremental cost-effectiveness ratio was $314 per additional case detected and $73 per additional case correctly diagnosed. Use of pharmacologic dilation and health care specialists' fees were the most important cost drivers. INTERPRETATION: The study showed that a compound teleophthalmology program in a semiurban community would be more effective but more costly than in person examination. The findings raise the question of whether the benefits of pharmacy-based teleophthalmology in semiurban areas, where in-person examination is still available, are equivalent to those observed in remote communities. Further study is needed to investigate the impact of this program on the prevention of severe vision loss and quality of life in a semiurban setting. PMID- 27280121 TI - In Vivo GFP Knockdown by Cationic Nanogel-siRNA Polyplexes. AB - RNA interference (RNAi) is a powerful tool to treat diseases and elucidate target gene function. Prior to clinical implementation, however, challenges including the safe, efficient and targeted delivery of siRNA must be addressed. Here, we report cationic nanogel nanostructured polymers (NSPs) prepared by atom transfer radical polymerization (ATRP) for in vitro and in vivo siRNA delivery in mammalian models. Outcomes from siRNA protection studies suggested that nanogel NSPs reduce enzymatic degradation of siRNA within polyplexes. Further, the methylation of siRNA may enhance nuclease resistance without compromising gene knockdown potency. NSP-mediated RNAi treatments against Gapdh significantly reduced GAPDH enzyme activity in mammalian cell culture models supplemented with 10% serum. Moreover, nanogel NSP-mediated siRNA delivery significantly inhibited in vivo GFP expression in a mouse model. GFP knockdown was siRNA sequence dependent and facilitated by nanogel NSP carriers. Continued testing of NSP/siRNA compositions in disease models may produce important new therapeutic options for patient care. PMID- 27280122 TI - Generation of Mouse iNKT Cell Lines. AB - Natural killer T (NKT) cells bridge the innate and adaptive arms of the immune system, and manipulating their effector functions can have therapeutic significances in the treatment of autoimmunity, transplant biology, infectious disease and cancer. This important lymphocyte subset regulates the immune system through their potent cytokine production following the recognition of lipid antigen present in the context of the MHC class I-like CD1d molecule, in addition their ability to directly mediate cytotoxicity. Here, we describe a method of expanding mouse invariant NKT (iNKT) cell lines from mononuclear cells isolated from the thymus, spleen, or liver using bone marrow derived dendritic cells. These iNKT cell lines can be used study their co-signaling requirements, cytokine profiles and cytotoxic functions which will greatly enhance our knowledge of iNKT cell biology. PMID- 27280124 TI - Compressed Sensing in On-Grid MIMO Radar. AB - The accurate detection of targets is a significant problem in multiple-input multiple-output (MIMO) radar. Recent advances of Compressive Sensing offer a means of efficiently accomplishing this task. The sparsity constraints needed to apply the techniques of Compressive Sensing to problems in radar systems have led to discretizations of the target scene in various domains, such as azimuth, time delay, and Doppler. Building upon recent work, we investigate the feasibility of on-grid Compressive Sensing-based MIMO radar via a threefold azimuth-delay Doppler discretization for target detection and parameter estimation. We utilize a colocated random sensor array and transmit distinct linear chirps to a small scene with few, slowly moving targets. Relying upon standard far-field and narrowband assumptions, we analyze the efficacy of various recovery algorithms in determining the parameters of the scene through numerical simulations, with particular focus on the l 1-squared Nonnegative Regularization method. PMID- 27280123 TI - Hippocampal place cell and inhibitory neuron activity in Disrupted-in schizophrenia-1 mutant mice: implications for working memory deficits. AB - BACKGROUND: Despite the prevalence of working memory deficits in schizophrenia, the neuronal mechanisms mediating these deficits are not fully understood1-3. Importantly, deficits in spatial working memory are identified in numerous mouse models that exhibit schizophrenia-like endophenotypes4-7. The hippocampus is one of the major brain regions that actively encodes spatial location, possessing pyramidal neurons, commonly referred to as 'place cells', that fire in a location specific manner8. This study tests the hypothesis that mice with a schizophrenia like endophenotype exhibit impaired encoding of spatial location in the hippocampus. METHODS: We recorded CA1 place cell activity in 6 control mice and 6 mice that carry a point mutation in the Disrupted-in-schizophrenia-1 gene (Disc1 L100P) and have previously been shown to exhibit deficits in spatial working memory4. RESULTS: The spatial specificity and stability of Disc1-L100P place cells were similar to wild-type place cells. Importantly, however, Disc1-L100P place cells exhibited a higher propensity to increase their firing rate in a single, large location of the environment, rather than multiple smaller locations, indicating a generalization in their spatial selectivity. Alterations in the signaling and numbers of CA1 putative inhibitory interneurons and decreased hippocampal theta (5-12Hz) power were also identified in the Disc1 L100P mice. CONCLUSIONS: The generalized spatial selectivity of Disc1-L100P place cells suggests a simplification of the ensemble place codes that encode individual locations and subserve spatial working memory. Moreover, these results suggest that deficient working memory in schizophrenia results from an impaired ability to uniquely code the individual components of a memory sequence. PMID- 27280125 TI - Students' Perceptions on an Interprofessional Ward Round Training - A Qualitative Pilot Study. AB - INTRODUCTION: Ward rounds are an essential activity for interprofessional teams in hospital settings and represent complex tasks requiring not only medical knowledge but also communication skills, clinical technical skills, patient management skills and team-work skills. The present study aimed to analyse final year students', nurses' as well as physiotherapists' views on a simulation-based interprofessional ward round training. METHODS: In two successive passes a total number of 29 final year students, nursing students and physiotherapy students (16 in the first run, 13 in the second) volunteered to participate in two standardized patient ward round scenarios: (1) patient with myocardial infarction, and (2) patient with poorly controlled diabetes. Views on the interprofessional ward round training were assessed using focus groups. RESULTS: Focus group based feedback contained two main categories (A) ward round training benefits and (B) difficulties. Positive aspects enfolded course preparation, setting of the training, the involvement of the participants during training and the positive learning atmosphere. Difficulties were seen in the flawed atmosphere and realization of ward rounds in the daily clinical setting with respect to inter-professional aspects, and course benefit for the different professional groups. CONCLUSION: The presented inter-professional ward round training represents a well received and valuable model of interprofessional learning. Further research should assess its effectiveness, processes of interprofessional interplay and transfer into clinical practice. PMID- 27280126 TI - Interprofessional education as part of becoming a doctor or physiotherapist in a competency-based curriculum. AB - INTRODUCTION: Interprofessional learning is a critical pre-requisite for future interprofessional work. Structural adaptations in education offer possibilities to introduce new concepts. Rheumatic and musculoskeletal diseases (RMD) are both prevented and treated by physicians and physiotherapists but the development of interprofessional roles is seldom part of curricula. PROJECT DESCRIPTION: A complex, longitudinal interprofessional educational approach for future doctors and physiotherapists was designed and implanted at various stages (anatomy, physical examination, pathology, therapy). Most segments of the RMD curriculum are now based on interprofessional classes. Student satisfaction with learning is continually and comparatively evaluated. Learning success is assessed with practical and written exams. RESULTS: Interprofessional teaching was first introduced in 2013 for 420 first-year and 360 fourth-year medical students, along with 40 first- and third-year physiotherapy majors. The satisfaction with teaching and learning is high and distinctly above average for all teaching areas (satisfaction RMD rated as 2.4; average for all is 3.3). The percentage of those who pass the final exam is 94%. 100% of the students surveyed support the continuation of this interprofessional unit. CONCLUSION: Interprofessional teaching of RMD can be successfully implemented for future physicians and physiotherapists at different learning levels. PMID- 27280127 TI - Interprofessional teaching and learning in the health care professions: A qualitative evaluation of the Robert Bosch Foundation's grant program "Operation Team". AB - AIM: Interprofessional teaching and learning is gaining significance in the health professions. At the same time, the development and implementation of such educational courses is demanding. Focusing on factors critical to success, the aim of this paper is to evaluate the experience gathered by eight grant projects in which interprofessional courses were designed. Emphasis is placed on the level of cooperation between the participating educational institutions, course content, the operative implementation of the course units and their permanent integration into curricula. METHOD: Data was collected in semi-structured, guideline-based interviews with project leaders and team members (n=43). University and vocational students who had attended the evaluated courses were also included in the survey (n=7) as a means to triangulate data. Analysis was carried out based on qualitative content analysis. RESULTS: A participatory, dialogue-centered model of cooperation appears to be most suited for developing and implementing courses. Belonging to the factors critical to success are the time when courses are offered, the conditions for attendance, the different teaching and learning cultures of the professions involved, preparation and deployment of instructors, and the role played by project coordination. Permanently integrating interprofessional units into medical curricula revealed itself to be difficult. CONCLUSION: While the development and realization of interprofessional courses can be achieved easily enough in projects, curricular integration of the new course units is challenging. In respect to the latter, not only a large amount of staffing resources and time are required, but also the creation of the necessary system-level structures, not just within the educational institutions (organizational development) but also in the frameworks governing the professions. PMID- 27280128 TI - Self-perceived attitudes toward interprofessional collaboration and interprofessional education among different health care professionals in pediatrics. AB - Interprofessional education (IPE) is the basis for interprofessional collaboration (IPC) in health care systems. It has beneficial effects for both patients and health care professionals. IPC is paramount for adequate care of patients and their families, especially in pediatrics. To determine the attitudes of medical doctors (n=121), nurses (n=15), psychologists (n=14), and social workers (n=19) toward IPE and IPC in a tertiary pediatric university teaching hospital, as well as the inpatient and outpatient settings in pediatrics, we developed a questionnaire with 21 items in four categories based on established questionnaires. All participants worked as part of interprofessional teams, and the overwhelming majority valued IPC highly. Most competencies important for IPC were acquired on the job. There was a substantial lack of interprofessional education, especially for medical doctors and psychologists. IPE still needs to be established as part of the undergraduate curriculum at German universities. PMID- 27280129 TI - Interprofessional education in Erlangen: A needs analysis and the conceptual work of a student working group. AB - INTRODUCTION: Interprofessional education (IPE) is receiving growing significance both nationally and internationally. Despite this, organizational and curricular changes are posing challenges. The level of need for IPE and how changes can be made to curricula and infrastructure were investigated at the University of Erlangen in Germany. METHOD: The student working group for interprofessional teaching (AGIL) has turned its attention to these issues. This group is composed of students from medicine, dentistry, molecular medicine, medical technology and speech therapy. In June, 2015, a needs analysis was carried out among the students in the study programs represented in the working group to assess the actual and target situation concerning IPE (n=1,105). In the search for answers and to better measure any needs, contact was sought with instructors. RESULTS: The majority of students feel that they are insufficiently educated in terms of interprofessional skills. A large proportion of the students wish to see expansion of the IPE offerings. Students also expressed a desire for additional spaces and welcomed the idea of an interprofessional learning center. AGIL began establishing interprofessional electives in October 2015. A concept for an interprofessional learning center was developed. DISCUSSION: Based on the survey results, a need for improvements to curricula and infrastructure can be seen; however, the results are limited to the student point of view. AGIL would like to establish more interprofessional electives. These courses would then facilitate curricular implementation. Modern ideas about study environments could be applied to IPE, in particular to promote informal forms of learning. Contact with instructors was crucial for the project work and should be expanded. Realizing and financing the learning center in Erlangen are now the future goals of AGIL. The aim is to create a foundation for this purpose. PMID- 27280130 TI - Simulating a patient's fall as a means to improve routine communication: Joint training for nursing and fifth-year medical students. AB - BACKGROUND: Physicians and nursing staff interact as a team on a daily basis in hospital settings. However, both educational paths offer few opportunities to establish contact with the other professional group. Neither professional group can practice its later role with the other group in a "safe" learning environment. Routine interprofessional collaboration is described as being in need of great improvement and carries with it the potential for conflict. To improve interprofessional communication and task management, a simulation-based emergency training session for nursing students and fifth-year medical students was developed at the KRH Klinikum Nordstadt in Hanover, Germany. As a pilot project, the course was held twice in the form of a one-day session with ten nursing and four medical students. PROJECT: Using the example of a patient's fall, course participants were able to observe and actively treat multiple simulated patients. Following each simulation the trainer conducted a comprehensive debriefing. The course was then evaluated using a questionnaire. RESULTS: The evaluation of the team training showed a high level of acceptance among the two participating professional groups. On a scale of 1 (hardly applicable) to 5 (strongly applicable), the course was given a 4 by both professional groups for its relevance to daily work. In the open-ended written responses praise was specifically given for the opportunity to learn how to switch perspectives as a result of the simulation exercises. CONCLUSION: A common emergency on the hospital ward offers a good opportunity to establish and practice interprofessional team skills. With the knowledge gained about communication and the ability to change viewpoints, participants are able to improve their team skills. Participants demonstrated a high degree of acceptance for the training program. PMID- 27280131 TI - First Contact: interprofessional education based on medical students' experiences from their nursing internship. AB - GOAL: The aim of the course "interprofessional communication and nursing" is to reflect medical students' experiences from the nursing internship. The content of the course focuses on barriers and support of interprofessional communication as a foundation for teamwork between nursing professionals and physicians. The nursing internship is for most medical students the first contact with nursing professionals and can lead to perceptions about the other group that might hinder interprofessional teamwork and consequently harm patients. To meet the demographic challenges ahead it is important to emphasize interprofessional education in the study of medicine and better prepare future physicians for interprofessional collaboration. METHOD: The design of the course includes an assessment of a change in the students' perceptions about nursing and interprofessional communication. The first class meeting presents the starting point of the assessment and visualizes students' perceptions of nursing and medicine. The content of the following class meetings serve to enhance the students' knowledge about nursing as a profession with its own theories, science and scholarship. In addition, all students have to write a research paper that entails to interview one nursing professional and one physician about their ideas of interprofessional communication and to compare the interviews with their own experiences from the nursing internship. To access what students learned during the course a reflective discussion takes place at the last meeting combined with an analysis of the students' research papers. RESULTS: The assessment of the students' perceptions about the nursing profession and the importance of successful interprofessional communication showed a new and deeper understanding of the topic. They were able to identify barriers and support measures of interprofessional communication and their own responsibilities as part of a team. CONCLUSION: Interprofessional education is an important part of medical education and should be a topic from the beginning. The assessment of the course shows that it is possible and important to integrate the topic early in the curriculum. PMID- 27280132 TI - The Conversion of a Peer Teaching Course in the Puncture of Peripheral Veins for Medical Students into an Interprofessional Course. AB - OBJECTIVE: There is a great interest on both a national and international level in promoting cooperation between different occupational groups within the healthcare professions through interprofessional education (IPE) [1], [2], [3]. Within this project, a peer teaching course on the puncture of peripheral veins was therefore converted from a course for medical students into an IPE learning unit. Students from different occupational groups were to learn within the context of this course, according to the definition from the World Health Organisation (WHO), with and from each other [1]. PROJECT DESCRIPTION: This course constituted a small group class in the peer teaching format. The didactic principle was based on the idea that the students were to practice the respective practical skills in pairs and give each other reciprocal feedback. Together with the Department for Health at the Bern University of Applied Sciences (BUAS) and the Bern Center of Higher Education of Nusing (BCHEN), the course, which was conducted by the Institute of Medical Education at the University of Bern (IME), was converted into a voluntary IPE pilot project. Students from all three institutions were represented in terms of participants as well as tutors. RESULTS: The course was evaluated very positively by participants, peer tutors and the participating institutions. By means of an OSCE, it could be proven that the course content had been successfully imparted. On the basis of these results, it was determined that the course should be compulsory in the future for students at all three institutions. DISCUSSION: The evaluation results show the successful conversion of the course into an IPE format within the context of the pilot project. The interactive format of the course created the prerequisite that the students from different professional groups learned with and from each other in actuality, and did not just study the same objectives at the same time as with multiprofessional learning. Cooperation between the three institutions is a cornerstone for the development of a research structure which may examine the effect of IPE in the future. PMID- 27280133 TI - Evaluation of interprofessional education: lessons learned through the development and implementation of an interprofessional seminar on team communication for undergraduate health care students in Heidelberg - a project report. AB - INTRODUCTION: This project report describes the development, "piloting" and evaluation of an interprofessional seminar on team communication bringing together medical students and Interprofessional Health Care B.Sc. students at the Medical Faculty of Heidelberg University, Germany. PROJECT DESCRIPTION: A five member interprofessional team collaborated together on this project. Kolb's experiential learning concept formed the theoretical foundation for the seminar, which explored three interprofessional competency areas: team work, communication and values/ethics. Evaluation for the purposes of quality assurance and future curricula development was conducted using two quantitative measures: descriptive analysis of a standardized course evaluation tool (EvaSys) ANOVA analysis of the German translation of the University of the West of England Interprofessional Questionnaire (UWE-IP-D). RESULTS: The key finding from the standardized course evaluation was that the interprofessional seminars were rated more positively [M=2.11 (1 most positive and 5 most negative), SD=1, n=27] than the monoprofessional seminars [M=2.55, SD=0.98, n=90]. The key finding from the UWE IP-D survey, comparing pre and post scores of the interprofessional (IP) (n=40) and monoprofessional (MP) groups (n=34), was that significant positive changes in mean scores for both groups towards communication, teamwork and interprofessional learning occurred. CONCLUSIONS: Lessons learnt included: a) recognising the benefit of being pragmatic when introducing interprofessional education initiatives, which enabled various logistical and attitudinal barriers to be overcome; b) quantitative evaluation of learning outcomes alone could not explain positive responses or potential influences of interprofessional aspects, which highlighted the need for a mixed methods approach, including qualitative methods, to enrich judgment formation on interprofessional educational outcomes. PMID- 27280134 TI - Communication in Health Professions: A European consensus on inter- and multi professional learning objectives in German. AB - BACKGROUND AND AIM: Communication is object of increasing attention in the health professions. Teaching communication competencies should already begin in undergraduate education or pre-registration training. The aim of this project was to translate the Health Professions Core Communication Curriculum (HPCCC), an English catalogue of learning objectives, into German to make its content widely accessible in the German-speaking countries. This catalogue lists 61 educational objectives and was agreed on by 121 international communication experts. A European reference framework for inter- and multi-professional curriculum development for communication in the health professions in German-speaking countries should be provided. METHOD: The German version of the HPCCC was drafted by six academics and went through multiple revisions until consensus was reached. The learning objectives were paired with appropriate teaching and assessment tools drawn from the database of the teaching Committee of the European Association for Communication Health Care (tEACH). RESULTS: The HPCCC learning objectives are now available in German and can be applied for curriculum planning and development in the different German-speaking health professions, the educational objectives can also be used for inter-professional purposes. Examples for teaching methods and assessment tools are given for using and implementing the objectives. CONCLUSION: The German version of the HPCCC with learning objectives for communication in health professions can contribute significantly to inter- and multi-professional curriculum development in the health care professions in the German-speaking countries. Examples for teaching methods and assessment tools from the materials compiled by tEACH supplement the curricular content and provide suggestions for practical implementation of the learning objectives in teaching and assessment. The relevance of the German HPCCC to the processes of curriculum development for the various health professions and inter professional approaches should be the subject of further evaluation. PMID- 27280135 TI - Design and evaluation of an IPE module at the beginning of professional training in medicine, nursing, and physiotherapy. AB - AIM: Interprofessional education (IPE) is a central feature of modern education in the health care professions. Despite this, empirically founded and systematically structured IPE courses are absent from many curricula. To answer the WHO's call for improved interprofessional collaboration in the health care system, a seminar was designed, implemented and evaluated. The target group consisted of students beginning nursing and medical studies (first and second semesters) and physiotherapy students (first year of training). The aim was to develop a basic IPE module focusing not only on the demands placed by academia and politics, but also the interests of the target group. This module was evaluated on the basis of the modified four-level Kirkpatrick approach. METHOD: Based on focus group interviews analyzed qualitatively using Mayring's content analysis, it was possible to define five learning objectives and develop four practice-oriented modules. The seminar was then implemented and evaluated using written pre- and post-seminar evaluations and group discussions. RESULTS: Analysis confirmed the success of the IPE concept in that the seminar was positively rated by attendees not only in terms of their immediate reactions, but also attitude, knowledge and skills according to Kirkpatrick. CONCLUSION: In the future, it is intended to offer the IPE module on a permanent basis and assess the competencies acquired in the seminar using observation. Courses to ensure sustained learning outcomes would also be desirable. PMID- 27280136 TI - The subjective experience of collaboration in interprofessional tutor teams: A qualitative study. AB - AIM: The Center for Interprofessional Training in Medicine at the Faculty of Medicine Carl Gustav Carus at the Technische Universitat Dresden, Germany, has offered courses covering interprofessional material since the winter semester 2014/15. The unusual feature of these courses is that they are co-taught by peer tutors from medicine and nursing. This study investigates the subjective experiences of these tutors during the collaborative preparation and teaching of these tutorials with the aim of identifying the effects of equal participation in the perceptions and assessments of the other professional group. METHOD: Semi structured, guideline-based interviews were held with six randomly selected tutors. The interviews were analyzed using structuring content analysis. RESULTS: The results show that collaborative work led to reflection, mostly by the university student tutors, on the attitudes held. However, the co-tutors from each professional group were perceived to different degrees as being representative of those in their profession. Asked to master a shared assignment in a non-clinical context, the members of the different professional groups met on equal footing, even if the medical students had already gathered more teaching experience and thus mostly assumed a mentoring role over the course of working on and realizing the teaching units. The nursing tutors were primarily focused on their role as tutor. Both professional groups emphasized that prior to the collaboration they had an insufficient or no idea about the theoretical knowledge or practical skills of the other professional group. Overall, the project was rated as beneficial, and interprofessional education was endorsed. CONCLUSION: In the discussion, recommendations based on the insights are made for joint tutor training of both professional groups. According to these recommendations, harmonizing the teaching abilities of all tutors is essential to ensure equality during cooperation. Ideally, training programs should be attended together by medical and nursing students to emphasize their shared identity as "tutor". PMID- 27280137 TI - Properties, promotive and obstructive conditions of multi-professional teaching and learning of health professions and non-health professions: an explorative survey from the perspective of teachers. AB - OBJECTIVE: Care for people with dementia is considered a multi-professional challenge that requires a collaborative approach between health professionals and non-health professionals. Didactic strategies to ensure the same qualifications across these occupational groups are lacking. This article presents the joint learning of selected properties and promotive and obstructive conditions, using the example of a multi-professional Master's programme. It subsequently draws conclusions for didactic concepts. METHODOLOGY: The perceptions of 12 teachers on this Master's programme, all representing different professions, were determined by using a qualitative exploratory survey on the three stated dimensions. With the aid of a summarising content analysis, their statements were condensed and abstracted so as to deduce appropriate requirements for methodical and didactic learning scenarios. RESULTS: In view of the fact that the students have very varied previous knowledge, the main challenge is finding a balance between expertise and tediousness. Establishing essential and common expertise, as well as sensitivity for different perspectives, is made particularly difficult by the fact that health and non-health professions differ greatly in terms of methods and approaches. For a successful outcome, the content focal points and didactic and methodical concepts for a learning group need to take into account the composition of that specific group. Recourse to didactic standard concepts is only possible to a limited extent. CONCLUSIONS: The aim of joint teaching and learning of health and non-health professionals is to enhance the understanding of a profession: This is done by making individuals aware of their role in the chain of care, so they can recognise and organise the mutual conditionality of their own and external professional contributions. PMID- 27280138 TI - Communicative positioning of one's own profession in interprofessional settings. AB - AIM: Interprofessional education (IPE) is taking on increasing importance in our complex healthcare system and receiving ever greater attention in the teaching of health science. The majority of concepts and methods employed in this area are based on normative ideas about interprofessional cooperation and only seldom based on empirical research. This paper is an initial attempt to augment this deductive approach with an inductive perspective for the purpose of subsequently providing empirical support for IPE teaching methods. METHOD: Drawing on the qualitative approach to linguistic conversation analysis, language-based professional markers are identified on the basis of recorded classroom simulations with nursing and midwifery students; it is assumed that these markers are significant in relevant interprofessional communication processes and, as a result, influence actual collaboration between the health professions. These markers are classified and commented on, and their importance to teaching and practical implementation in interprofessional interaction is emphasized. RESULTS: Students routinely use various professional markers in simulations. However, these occur much less frequently than initially expected, except when marking difference in relation to physicians. At the same time, all the interactions are shaped by pronounced self-presentation among the students, and this comprises a large aspect of the interactions observed here. Profession-specific communication and differentiation processes also appear to be slow in establishing themselves in terms of students delegating tasks or voicing expectations. In addition, the role of "student" has a function that should not be underestimated in these interactions. CONCLUSION: Professional markers are an essential component of interprofessional communication and are based on numerous, observable linguistic phenomena, of which only a few are presented here. This empirical approach has not yet appeared in the discourse surrounding IPE; however, it is, in the authors' opinion, not only necessary to compare interprofessional interactions with lived reality, but also to be in a position to operationalize interprofessional practice and ultimately assign it to competency areas. For this reason, further empirical observations and analyses are needed to tighten the still unclear definition of interprofessional communication and to develop empirically founded, measurable criteria for teaching and testing. PMID- 27280139 TI - Fostering interprofessional communication through case discussions and simulated ward rounds in nursing and medical education: A pilot project. AB - BACKGROUND: Poor communication between physicians and nursing staff could result in inadequate interprofessional collaboration with negative effects on patient health. In order to ensure optimal health care for patients, it is important to strengthen interprofessional communication and collaboration between physicians and nurses during their education. AIM: The aim of this project is to foster communication for medical and nursing students through interprofessional case discussions and simulated ward rounds as a form of training. METHOD: In 2013-15 a total of 39 nursing students and 22 medical students participated in eight seminars, each covering case discussions and simulated ward rounds. The seminar was evaluated based on student assessment of the educational objectives. RESULTS: Students who voluntarily signed up for the seminar profited from the interprofessional interaction and gathered positive experiences working in a team. CONCLUSION: Through practicing case discussions and ward rounds as a group, interprofessional communication could be fostered between medical and nursing students. Students took advantage of the opportunity to ask those from other profession questions and realized that interprofessional interaction can lead to improved health care. PMID- 27280140 TI - Interprofessional practice in health care: an educational project with four learning sequences for students from six study programs. AB - INTRODUCTION: In response to demographic changes and the growing complexity of healthcare demands, national and international organizations are requiring greater cooperation among the health professions. Implementation of interprofessional learning programs within study programs in medicine, midwifery, nursing, and therapy is still rare. The first projects are currently underway in Germany. This paper presents the experience gathered by the organizers as interprofessional courses for six study programs were implemented. PROJECT DESCRIPTION: As part of the collaborative project "Interprofessional Practice in Health Care" between the Medical School at the Ruhr University in Bochum and the Department for Applied Health Sciences at the Hochschule fur Gesundheit, interprofessional curricular units were developed, taught and evaluated with the aim of establishing permanent and joint curricular structures at the two German universities. Imparting communication skills, knowledge of and appreciation for the work performed by the other health professions, as well as having students reflect on their own professional roles and responsibilities, were the focus of four curricular units. Students worked together in small interprofessional groups. RESULTS: A total of 220 students enrolled in occupational therapy, midwifery, speech therapy, medicine, nursing, and physiotherapy participated in small-group seminars. When conducting and implementing the seminars, administrative and methodological challenges became apparent, and this should be taken into consideration in regard to any future development of interprofessional courses. Integration into existing curricula, along with finding time in the various schedules and appropriate classroom space for small groups, were among the challenges faced. For over 86% of the students it was important that students from all six of the degree programs involved participated in the project. A detailed analysis of the content and evaluation will follow. CONCLUSION: The value of the project's aim to include as many study programs in the health professions and medicine as possible was confirmed by the participating students. However, accomplishing this requires a substantial amount of organizational effort in terms of scheduling, finding classroom space and integration into existing curricula. Careful attention must be given specifically to the coordination of monoprofessional and interprofessional teaching units. PMID- 27280141 TI - Interprofessional peer-assisted learning as a low-threshold course for joint learning: Evaluation results of the interTUT Project. AB - BACKGROUND AND OBJECTIVE: The delivery of needs-based health care services requires a team-based and collaborative approach of different health professionals, which is not yet sufficienctliy implemented on a day to day basis. Interprofessional learning activities aim to respond to this in future. The cross university pilot project interTUT used peer-assisted learning approaches and extracurricular tutorials in order address this issue. METHODOLOGY: During the pilot phase, eight students and trainees have been acquired. Together, they prepared and led four extracurricular tutorials on core topics of interprofessional cooperation and documented them in procedure manuals. The course was evaluated using a standardized participant survey (n=72) and two focus groups (n=3, n=5) in which participants were asked to reflect on their individual learning experiences. Descriptive statistics were used to analyze the survey data and the focus group material was interpreted using qualitative content analysis. RESULTS: The results indicated a high level of satisfaction, acceptance of and further demand for peer-supported learning activities. The students and trainees reported changed attitudes and subjective knowledge growth regarding the other professional groups. The constructive learning atmosphere as well as having access to a forum for interprofessional exchange were equally valued. CONCLUSIONS: Extracurricular tutorials offer a low-threshold and very promising point of contact for the facilitation of interprofessional teaching and learning. However, this should be viewed against the background that, as part of the pilot project, only a small number of students and trainees who were already interested in the topic could be reached by this optional course. A comprehensive, long-term trial of this teaching and learning format, its linkage to curricular courses, and further research on its education-specific and practice-related effects are, therefore, necessary. PMID- 27280142 TI - Comprehension through cooperation: Medical students and physiotherapy apprentices learn in teams - Introducing interprofessional learning at the University Medical Centre Mannheim, Germany. AB - AIM: In order to better prepare future health care professionals for interprofessional cooperation, interprofessional learning sessions for medical students and physiotherapy apprentices were developed at the University Medical Centre Mannheim, Germany. The experience gained from designing, implementing and evaluating these learning sessions is presented and discussed. METHOD: A total of 265 medical students and 43 physiotherapy apprentices attended five interprofessional learning sessions. Of these, 87-100% responded to closed and open-ended questions on a self-developed questionnaire (24 items). The responses regarding self-reported learning gains, benefit, motivation and satisfaction with the sessions were analyzed separately by professions. RESULTS: The learning sessions were well received by both groups. More than 75% of all participants were of the opinion that they could not have learned the new material in a better way. Significant differences between the medical students and the physiotherapy apprentices were mainly found with regard to perceived learning gains, which physiotherapy apprentices reported as being lower. Positive aspects of interprofessionalism were most often emphasized in the responses to the open ended questions. Most frequently criticized were organizational aspects and a lack of perceived learning gains. CONCLUSION: The introduction of interprofessional learning entails great effort in terms of organizational and administrative challenges. However, the project is considered worthwhile because the interprofessional aspects of the learning sessions were indeed valued by the participants. Permanently including and expanding interprofessional learning in the curricula of both professions longitudinally is therefore something to strive for. PMID- 27280143 TI - Interprofessional Learning - Development and Implementation of Joint Medical Emergency Team Trainings for Medical and Nursing Students at Universitatsmedizin Greifswald. AB - INTRODUCTION: Interprofessional collaboration is of great importance in clinical practice, particularly in the field of emergency medicine. The professions involved in providing emergency care must work hand in hand, and tasks and routines must be coordinated effectively. However, medical and nursing students have only few opportunities to experience interprofessional cooperation during their formal training. Addressing this situation, the Department of Anesthesiology and the Vocational School of Greifswald University Medical School initiated a project to increase patient safety by integrating interprofessional human factor training into the curriculum of both health professions. This manuscript addresses how an interprofessional course module focusing on clinical emergency medicine can be taught with an emphasis on competency and problem solving. In addition, it was important to identify suitable instruments for systematic quality development and assurance of this teaching and learning format. PROJECT DESCRIPTION: The aim of the project, which took place from October 2013 to September 2015, was the development, implementation and evaluation of a simulation-based, interprofessional course module on clinical emergency medicine. Target groups were medical and nursing students. Modern pedagogical models and methods were applied to the design and teaching of the course content. The project was carried out in separate phases: definition, planning, practical implementation, evaluation and documentation. The project was accompanied by systematic quality development. Established guidelines for quality centered school development were applied to quality development, assurance and evaluation. RESULTS: Over two years, a 16 credit-hour course module was developed and then taught and evaluated during the 2014 and 2015 summer semesters. A total of 120 medical students and 120 nursing students participated in the course module. Eighteen teachers from medicine and nursing were trained as instructors and assisted by 12 student tutors. Regular evaluations focused on different aspects of the project, using instruments for empirical educational research. Excellent ratings given to the course by the attendees indicate a high degree of satisfaction in both participating professions regarding course design and content, as well as the quality of teaching. DISCUSSION: In a position paper, the GMA committee on Interprofessional Education in Health Professions issued recommendations for interprofessional education. The recommendations given for teaching and quality assurance are drawn upon here, and relevant examples from the course concept presented. CONCLUSION: The design of the course corresponds to the recommendations of the GMA committee on Interprofessional Education in the Health Professions. Based on these, and considering the satisfactory evaluations, both continuation and further development of this interprofessional teaching format are justified. PMID- 27280144 TI - Recommendations to enhance constructivist-based learning in Interprofessional Education using video-based self-assessment. AB - INTRODUCTION: Interprofessional collaboration is crucial to the optimization of patient care. AIM: This paper aims to provide recommendations for implementing an innovative constructivist educational concept with the core element of video based self-assessment. METHODOLOGY: A course for students in medicine, physiotherapy, and nursing was developed through interprofessional, cross institutional collaboration. The course consisted of drawing on prior knowledge about the work done by each professional group in regard to a specific clinical scenario and an interprofessional treatment situation, filming a role play of this treatment situation, and a structured self-assessment of the role play. We evaluated the preparation and implementation of the three courses conducted thus far. Concrete recommendations for implementation were made based on evaluation sheets (students), open discussions (tutors, instructors, institutions) and recorded meeting minutes (project managers, project participants). RESULTS: Basic recommendations for implementation include: selecting appropriate criteria for self-assessment and a simulated situation that offers members of each professional group an equal opportunity to act in the role play. In terms of administrative implementation we recommend early coordination among the professions and educational institutions regarding the target groups, scheduling and attendance policy to ensure participant recruitment across all professions. Procedural planning should include developing teaching materials, such as the case vignette and treatment scenario, and providing technical equipment that can be operated intuitively in order to ensure efficient recording. CONCLUSION: These recommendations serve as an aid for implementing an innovative constructivist educational concept with video-based self-assessment at its core. PMID- 27280145 TI - Berlin in Motion: Interprofessional teaching and learning for students in the fields of medicine, occupational therapy, physiotherapy and nursing (INTER-M-E-P P). AB - AIM: The Berlin project "Interprofessional teaching and learning in medicine, occupational therapy, physiotherapy and nursing" (INTER-M-E-P-P) pursues the goal of developing and testing interprofessional courses in an exemplary manner, and then implement these into their regular study programs. METHOD: Under the direction of a steering committee of the participating institutions, professions and status groups, interprofessional courses were designed, carried out and evaluated. Specific to this project are the participation of students in the steering committee, and the accompanying of external supervision. The evaluation integrates the perspectives of all project participants, and combines quantitative and qualitative methods. RESULTS: INTER-M-E-P-P established cooperative structures between the participating universities and programs. Three courses were designed, taught and evaluated in an interprofessional manner. The various curricula, organizational patterns and locations of the study paths led to a great need for resources in regard to planning and implementation. This process can be made difficult by any stereotypes or preconceptions inherent to those doing the planning; however, under external supervision, the individual professional viewpoints can still be broadened and enriched. CONCLUSION: A sustainable implementation of interprofessional education into the curricula of health science study programs is currently complicated by barriers such as different geographical locations and differing university regulations concerning study and testing. Implementation will require long-term support at the university as well as at political levels. PMID- 27280146 TI - Improving competencies in evidence-based dementia care: Results from a pilot study on a novel inter-professional training course (the KOMPIDEM project). AB - OBJECTIVE: In order to address well-known challenges in dementia care, an inter professional course was developed to improve medical students' and nursing students' competencies in the provision of evidence-based care for people with dementia. The course comprises lectures, problem-based learning (PbL) tutorials and visitations to care facilities. A pilot study was conducted to evaluate the acceptance and feasibility of the inter-professional course. METHODOLOGY: Alongside preliminary implementation of the newly developed course, a pre-post survey was carried out involving all participating students. The questionnaire contained standardized and open-ended questions on participants' views regarding the quality and relevance of several course components and characteristics. The data were analyzed by means of descriptive statistics. RESULTS: When the course was offered the first time, multiple barriers became evident, leading to premature course termination and subsequent revision of the curriculum. When the revised course was offered, 10 medical students and 8 nursing students participated. The course proved feasible, and the median overall quality was rated as "2" (IQR 2-3) at a rating scale ranging from 1 (very good) to 6 (inadequate). Following aspects were most frequently judged positively: the course's inter-professional scope, the visitations to care facilities and the PbL tutorials. Potential for improvement was particularly noted with regard to a more distinct focus on well-defined, mainly practical learning outcomes. There were no indications of systematic between-group differences in the medical and nursing students' perceptions of the course program. CONCLUSIONS: The results confirmed the feasibility of the inter-professional course on dementia care and the relevance of its inter-professional scope. However, to ensure sustainable course implementation in the long term, further program adaptations based on current findings and further evaluation studies focusing on objective parameters of the process and outcome quality are required. PMID- 27280147 TI - More terminological clarity in the interprofessional field - a call for reflection on the use of terminologies, in both practice and research, on a national and international level. AB - The terminology which has been used up until now within interprofessional healthcare has been characterised by a certain definitional weakness, which, among other factors, has been caused by an uncritical adoption of language conventions and a lack of theoretical reflection. However, as terminological clarity plays a significant role in the development and profiling of a discipline, the clarification and definition of commonly-used terminology has manifested itself as a considerable objective for the interprofessional research community. One of the most important journals for research in the area of interprofessional education and care, the Journal of Interprofessional Care, has expanded its author guidelines relating to terminology, modeled after the conceptual considerations of the research group around Barr et. al and Reeves et al. A German translation of the suggested terms therein has been presented in this contribution, and discussed in light of the challenges to a possible adaptation for the German-speaking world. The objective is to assist communication in practice and research in becoming clearer, while promoting an increasing awareness to and the transparency of determined definitions and terminologies. PMID- 27280148 TI - Collaboration, cooperation, communication, contact and competencies. PMID- 27280149 TI - Special edition booklet: Interprofessional Training - Published by the Robert Bosch Stiftung and the Gesellschaft fur Medizinische Ausbildung. PMID- 27280150 TI - Triclosan antimicrobial polymers. AB - Triclosan antimicrobial molecular fluctuating energies of nonbonding electron pairs for the oxygen atom by ether bond rotations are reviewed with conformational computational chemistry analyses. Subsequent understanding of triclosan alternating ether bond rotations is able to help explain several material properties in Polymer Science. Unique bond rotation entanglements between triclosan and the polymer chains increase both the mechanical properties of polymer toughness and strength that are enhanced even better through secondary bonding relationships. Further, polymer blend compatibilization is considered due to similar molecular relationships and polarities. With compatibilization of triclosan in polymers a more uniform stability for nonpolar triclosan in the polymer solid state is retained by the antimicrobial for extremely low release with minimum solubility into aqueous solution. As a result, triclosan is projected for long extended lifetimes as an antimicrobial polymer additive. Further, triclosan rapid alternating ether bond rotations disrupt secondary bonding between chain monomers in the resin state to reduce viscosity and enhance polymer blending. Thus, triclosan is considered for a polymer additive with multiple properties to be an antimicrobial with additional benefits as a nonpolar toughening agent and a hydrophobic wetting agent. The triclosan material relationships with alternating ether bond rotations are described through a complete different form of medium by comparisons with known antimicrobial properties that upset bacterial cell membranes through rapid fluctuating mechanomolecular energies. Also, triclosan bond entanglements with secondary bonding can produce structural defects in weak bacterial lipid membranes requiring pliability that can then interfere with cell division. Regarding applications with polymers, triclosan can be incorporated by mixing into a resin system before cure, melt mixed with thermoplastic polymers that set on cooling into a solid or alternatively applied as a coating through several different methods with dissolving into an organic solvent and dried on by evaporation as a common means. PMID- 27280151 TI - Visuomotor Learning Generalizes Around the Intended Movement. AB - Human motor learning is useful if it generalizes beyond the trained task. Here, we introduce a new idea about how human visuomotor learning generalizes. We show that learned reaching movements generalize around where a person intends to move (i.e., aiming direction) as opposed to where they actually move. We used a visual rotation paradigm that allowed us to disentangle whether generalization is centered on where people aim to move, where they actually move, or where visual feedback indicates they moved. Participants reached to a visual target with their arm occluded from view. The cursor feedback was rotated relative to the position of their unseen hand to induce learning. Participants verbally reported their aiming direction, reached, and then were shown the outcome. We periodically introduced single catch trials with no feedback to measure learning. Results showed that learning was maximal at the participants' aiming location, and not at the actual hand position or where the cursor was displayed. This demonstrates that visuomotor learning generalizes around where we intend to move rather than where we actually move, and thus introduces a new role for cognitive processes beyond simply reducing movement error. PMID- 27280152 TI - The Presence of Real Food Usurps Hypothetical Health Value Judgment in Overweight People. AB - To develop more ecologically valid models of the neurobiology of obesity, it is critical to determine how the neural processes involved in food-related decision making translate into real-world eating behaviors. We examined the relationship between goal-directed valuations of food images in the MRI scanner and food consumption at a subsequent ad libitum buffet meal. We observed that 23 lean and 40 overweight human participants showed similar patterns of value-based neural responses to health and taste attributes of foods. In both groups, these value based responses in the ventromedial PFC were predictive of subsequent consumption at the buffet. However, overweight participants consumed a greater proportion of unhealthy foods. This was not predicted by in-scanner choices or neural response. Moreover, in overweight participants alone, impulsivity scores predicted greater consumption of unhealthy foods. Overall, our findings suggest that, while the hypothetical valuation of the health of foods is predictive of eating behavior in both lean and overweight people, it is only the real-world food choices that clearly distinguish them. PMID- 27280153 TI - Topographical Organization of Attentional, Social, and Memory Processes in the Human Temporoparietal Cortex. AB - The temporoparietal junction (TPJ) is activated in association with a large range of functions, including social cognition, episodic memory retrieval, and attentional reorienting. An ongoing debate is whether the TPJ performs an overarching, domain-general computation, or whether functions reside in domain specific subdivisions. We scanned subjects with fMRI during five tasks known to activate the TPJ, probing social, attentional, and memory functions, and used data-driven parcellation (independent component analysis) to isolate task-related functional processes in the bilateral TPJ. We found that one dorsal component in the right TPJ, which was connected with the frontoparietal control network, was activated in all of the tasks. Other TPJ subregions were specific for attentional reorienting, oddball target detection, or social attribution of belief. The TPJ components that participated in attentional reorienting and oddball target detection appeared spatially separated, but both were connected with the ventral attention network. The TPJ component that participated in the theory-of-mind task was part of the default-mode network. Further, we found that the BOLD response in the domain-general dorsal component had a longer latency than responses in the domain-specific components, suggesting an involvement in distinct, perhaps postperceptual, computations. These findings suggest that the TPJ performs both domain-general and domain-specific computations that reside within spatially distinct functional components. PMID- 27280154 TI - Somatosensory Representations Link the Perception of Emotional Expressions and Sensory Experience. AB - Studies of human emotion perception have linked a distributed set of brain regions to the recognition of emotion in facial, vocal, and body expressions. In particular, lesions to somatosensory cortex in the right hemisphere have been shown to impair recognition of facial and vocal expressions of emotion. Although these findings suggest that somatosensory cortex represents body states associated with distinct emotions, such as a furrowed brow or gaping jaw, functional evidence directly linking somatosensory activity and subjective experience during emotion perception is critically lacking. Using functional magnetic resonance imaging and multivariate decoding techniques, we show that perceiving vocal and facial expressions of emotion yields hemodynamic activity in right somatosensory cortex that discriminates among emotion categories, exhibits somatotopic organization, and tracks self-reported sensory experience. The findings both support embodied accounts of emotion and provide mechanistic insight into how emotional expressions are capable of biasing subjective experience in those who perceive them. PMID- 27280155 TI - Excitability and Burst Generation of AVPV Kisspeptin Neurons Are Regulated by the Estrous Cycle Via Multiple Conductances Modulated by Estradiol Action. AB - The preovulatory secretory surge of gonadotropin-releasing hormone (GnRH) is crucial for fertility and is regulated by a switch of estradiol feedback action from negative to positive. GnRH neurons likely receive estradiol feedback signals via ERalpha-expressing afferents. Kisspeptin neurons in anteroventral periventricular nucleus (AVPV) are thought to be critical for estradiol-positive feedback induction of the GnRH surge. We examined the electrophysiological properties of GFP-identified AVPV kisspeptin neurons in brain slices from mice on the afternoon of diestrus (negative feedback) and proestrus (positive feedback, time of surge). Extracellular recordings revealed increased firing frequency and action potential bursts on proestrus versus diestrus. Whole-cell recordings were used to study the intrinsic mechanisms of bursting. Upon depolarization, AVPV kisspeptin neurons exhibited tonic firing or depolarization-induced bursts (DIB). Both tonic and DIB cells exhibited bursts induced by rebound from hyperpolarization. DIB occurred similarly on both cycle stages, but rebound bursts were observed more often on proestrus. DIB and rebound bursts were both sensitive to Ni(2+), suggesting that T-type Ca(2+) currents (I Ts) are involved. I T current density was greater on proestrus versus diestrus. In addition to I T, persistent sodium current (I NaP) facilitated rebound bursting. On diestrus, 4 aminopyridine-sensitive potassium currents contributed to reduced rebound bursts in both tonic and DIB cells. Manipulation of specific sex steroids suggests that estradiol induces the changes that enhance AVPV kisspeptin neuron excitability on proestrus. These observations indicate cycle-driven changes in circulating estradiol increased overall action potential generation and burst firing in AVPV kisspeptin neurons on proestrus versus diestrus by regulating multiple intrinsic currents. PMID- 27280157 TI - Tropism of CPMV to Professional Antigen Presenting Cells Enables a Platform to Eliminate Chronic Infections. AB - Chronic viral infections (e.g., HIV, HBV, HCV) represent a significant source of morbidity and mortality with over 500 million people infected worldwide. Dendritic cells (DCs) and macrophages are key cell types for productive viral replication and persistent systemic infection. We demonstrate that the plant virus cowpea mosaic virus (CPMV) displays tropism for such antigen presenting cells in both mice and humans, thus making it an ideal candidate for targeted drug delivery toward viral infections. Furthermore, we show inhibition of a key host protein for viral infection, site-1 protease (S1P), using the small molecule PF-429242 in the model pathogen arenavirus lymphocytic choriomeningitis virus (LCMV) limits viral growth. By packaging PF-429242 in CPMV, we are able to control drug release and efficiently deliver the drug. This sets the groundwork for utilizing the natural tropism of CPMV for a therapeutic approach that specifically targets cell types most commonly subverted by chronic viruses. PMID- 27280156 TI - Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells. AB - The fluorescent dyes, Alexa Fluor 488 and 594 are commonly used to visualize dendritic structures and the localization of synapses, both of which are critical for the spatial and temporal integration of synaptic inputs. However, the effect of the dyes on synaptic transmission is not known. Here we investigated whether Alexa Fluor dyes alter the properties of synaptic currents mediated by two subtypes of AMPA receptors (AMPARs) at cerebellar stellate cell synapses. In naive mice, GluA2-lacking AMPAR-mediated synaptic currents displayed an inwardly rectifying current-voltage (I-V) relationship due to blockade by cytoplasmic spermine at depolarized potentials. We found that the inclusion of 100 um Alexa Fluor dye, but not 10 um, in the pipette solution led to a gradual increase in the amplitude of EPSCs at +40 mV and a change in the I-V relationship from inwardly rectifying to more linear. In mice exposed to an acute stress, AMPARs switched to GluA2-containing receptors, and 100 um Alexa Fluor 594 did not alter the I-V relationship of synaptic currents. Therefore, a high concentration of Alexa Fluor dye changed the I-V relationship of EPSCs at GluA2-lacking AMPAR synapses. PMID- 27280159 TI - A Conversation with Makoto Fujita. PMID- 27280158 TI - A Triple Crown of Sustainable Synthesis. PMID- 27280160 TI - Taming Toxic Algae Blooms. PMID- 27280161 TI - Mysteries in a Minimal Genome. PMID- 27280162 TI - Mind the Gap. PMID- 27280163 TI - Photoredox Catalysis Unlocks Single-Electron Elementary Steps in Transition Metal Catalyzed Cross-Coupling. AB - Since initial reports, cross-coupling technologies employing photoredox catalysts to access novel reactivity have developed with increasing pace. In this Outlook, prominent examples from the recent literature are organized on the basis of the elementary transformation enabled by photoredox catalysis and are discussed in the context of relevant historical precedent in stoichiometric organometallic chemistry. This treatment allows mechanistic similarities inherent to odd electron transition metal reactivity to be generalized to a set of lessons for future reaction development. PMID- 27280165 TI - The Optical Signature of Charges in Conjugated Polymers. AB - Electrical charge flowing through organic semiconductors drives many of today's mobile phone displays and television screens, suggesting an internally consistent model of charge-carrier properties in these materials to have manifested. In conjugated polymers, charges give rise to additional absorption of light at wavelengths longer than those absorbed by the electrically neutral species. These characteristic absorption bands are universally being related to the emergence of localized energy levels shifted into the forbidden gap of organic semiconductors due to local relaxation of the molecular geometry. However, the traditional view on these energy levels and their occupation is incompatible with expected changes in electron removal and addition energies upon charging molecules. Here, I demonstrate that local Coulomb repulsion, as captured by nonempirically optimized electronic-structure calculations, restores compatibility and suggests a different origin of the charge-induced optical transitions. These results challenge a widely accepted and long-established picture, but an improved understanding of charge carriers in molecular materials promises a more targeted development of organic and hybrid organic/inorganic (opto-)electronic devices. PMID- 27280164 TI - Synthetic Organic Electrochemistry: An Enabling and Innately Sustainable Method. AB - While preparative electrolysis of organic molecules has been an active area of research over the past century, modern synthetic chemists have generally been reluctant to adopt this technology. In fact, electrochemical methods possess many benefits over traditional reagent-based transformations, such as high functional group tolerance, mild conditions, and innate scalability and sustainability. In this Outlook we highlight illustrative examples of electrochemical reactions in the context of the synthesis of complex molecules, showcasing the intrinsic benefits of electrochemical reactions versus traditional reagent-based approaches. Our hope is that this field will soon see widespread adoption in the synthetic community. PMID- 27280166 TI - A Direct Mechanism of Ultrafast Intramolecular Singlet Fission in Pentacene Dimers. AB - Interest in materials that undergo singlet fission (SF) has been catalyzed by the potential to exceed the Shockley-Queisser limit of solar power conversion efficiency. In conventional materials, the mechanism of SF is an intermolecular process (xSF), which is mediated by charge transfer (CT) states and depends sensitively on crystal packing or molecular collisions. In contrast, recently reported covalently coupled pentacenes yield ~2 triplets per photon absorbed in individual molecules: the hallmark of intramolecular singlet fission (iSF). However, the mechanism of iSF is unclear. Here, using multireference electronic structure calculations and transient absorption spectroscopy, we establish that iSF can occur via a direct coupling mechanism that is independent of CT states. We show that a near-degeneracy in electronic state energies induced by vibronic coupling to intramolecular modes of the covalent dimer allows for strong mixing between the correlated triplet pair state and the local excitonic state, despite weak direct coupling. PMID- 27280167 TI - Bioorthogonal Chemical Activation of Kinases in Living Systems. AB - Selective manipulation of protein kinases under living conditions is highly desirable yet extremely challenging, particularly in a gain-of-function fashion. Here we employ our recently developed bioorthogonal cleavage reaction as a general strategy for intracellular activation of individual kinases. Site specific incorporation of trans-cyclooctene-caged lysine in place of the conserved catalytic lysine, in conjunction with the cleavage partner dimethyl tetrazine, allowed efficient lysine decaging with the kinase activity chemically rescued in living systems. PMID- 27280168 TI - Expedited Selection of NMR Chiral Solvating Agents for Determination of Enantiopurity. AB - The use of NMR chiral solvating agents (CSAs) for the analysis of enantiopurity has been known for decades, but has been supplanted in recent years by chromatographic enantioseparation technology. While chromatographic methods for the analysis of enantiopurity are now commonplace and easy to implement, there are still individual compounds and entire classes of analytes where enantioseparation can prove extremely difficult, notably, compounds that are chiral by virtue of very subtle differences such as isotopic substitution or small differences in alkyl chain length. NMR analysis using CSAs can often be useful for such problems, but the traditional approach to selection of an appropriate CSA and the development of an NMR-based analysis method often involves a trial-and-error approach that can be relatively slow and tedious. In this study we describe a high-throughput experimentation approach to the selection of NMR CSAs that employs automation-enabled screening of prepared libraries of CSAs in a systematic fashion. This approach affords excellent results for a standard set of enantioenriched compounds, providing a valuable comparative data set for the effectiveness of CSAs for different classes of compounds. In addition, the technique has been successfully applied to challenging pharmaceutical development problems that are not amenable to chromatographic solutions. Overall, this methodology provides a rapid and powerful approach for investigating enantiopurity that compliments and augments conventional chromatographic approaches. PMID- 27280169 TI - Isolation and Reactivity of Trifluoromethyl Iodonium Salts. AB - The strategic incorporation of the trifluoromethyl (CF3) functionality within therapeutic or agrochemical agents is a proven strategy for altering their associated physicochemical properties (e.g., metabolic stability, lipophilicity, and bioavailability). Electrophilic trifluoromethylation has emerged as an important methodology for installing the CF3 moiety onto an array of molecular architectures, and, in particular, CF3 lambda(3)-iodanes have garnered significant interest because of their unique reactivity and ease of handling. Trifluoromethylations mediated by these hypervalent iodine reagents often require activation through an exogenous Lewis or Bronsted acid; thus, putative intermediates invoked in these transformations are cationic CF3 iodoniums. These iodoniums have, thus far, eluded isolation and investigation of their innate reactivity (which has encouraged speculation that such species cannot be accessed). A more complete understanding of the mechanistic relevance of CF3 iodoniums is paramount for the development of new trifluoromethylative strategies involving lambda(3)-iodanes. Here, we demonstrate that CF3 iodonium salts are readily prepared from common lambda(3)-iodane precursors and exhibit remarkable persistence under ambient conditions. These reagents are competent electrophiles for a variety of trifluoromethylation reactions, and their reactivity is reminiscent of that observed when CF3 iodanes are activated using Lewis acids. As such, our results suggest the mechanistic relevance of CF3 iodonium intermediates in trifluoromethylative processes mediated by lambda(3)-iodanes. The isolation of CF3 iodonium salts also presents the unique opportunity to employ them more generally as mechanistic probes. PMID- 27280170 TI - Detection of Active Mammalian GH31 alpha-Glucosidases in Health and Disease Using In-Class, Broad-Spectrum Activity-Based Probes. AB - The development of small molecule activity-based probes (ABPs) is an evolving and powerful area of chemistry. There is a major need for synthetically accessible and specific ABPs to advance our understanding of enzymes in health and disease. alpha-Glucosidases are involved in diverse physiological processes including carbohydrate assimilation in the gastrointestinal tract, glycoprotein processing in the endoplasmic reticulum (ER), and intralysosomal glycogen catabolism. Inherited deficiency of the lysosomal acid alpha-glucosidase (GAA) causes the lysosomal glycogen storage disorder, Pompe disease. Here, we design a synthetic route for fluorescent and biotin-modified ABPs for in vitro and in situ monitoring of alpha-glucosidases. We show, through mass spectrometry, gel electrophoresis, and X-ray crystallography, that alpha-glucopyranose configured cyclophellitol aziridines label distinct retaining alpha-glucosidases including GAA and ER alpha-glucosidase II, and that this labeling can be tuned by pH. We illustrate a direct diagnostic application in Pompe disease patient cells, and discuss how the probes may be further exploited for diverse applications. PMID- 27280171 TI - Defining the spectrum of frontotemporal dementias associated with TARDBP mutations. AB - OBJECTIVES: We describe the largest series of patients with TARDBP mutations presenting with frontotemporal dementia (FTD) and review the cases in the literature to precisely characterize FTD diseases associated with this genotype. METHODS: The phenotypic characteristics of 29 TARDBP patients, including 10 new French and Dutch cases and 19 reviewed from the literature, were evaluated. RESULTS: The most frequent phenotype was a behavioral variant frontotemporal dementia (bvFTD), but a significant proportion (40%) of our patients had semantic (svFTD) or nonfluent variants (nfvFTD) at onset; and svFTD was significantly more frequent in TARDBP carriers than in other FTD genotypes (p < 0.001). Remarkably, only a minority (40%) of our patients secondarily developed amyotrophic lateral sclerosis (ALS). Two patients carried a homozygous mutation but strikingly different phenotypes (bvFTD and ALS) indicating that homozygosity does not result in a specific phenotype. Earlier age at onset in children than parent's generations, mimicking an apparent "anticipation" (21.8 +/- 9.3 years, p = 0.001), and possible reduced penetrance were present in most families. CONCLUSIONS: This study enlarges the phenotypic spectrum of TARDBP and will have important clinical implications: (1) FTD can be the only clinical manifestation of TARDBP mutations; (2) Initial language or semantic disorders might be indicative of a specific genotype; (3) Mutations should be searched in all FTD phenotypes after exclusion of major genes, even in the absence of ALS in the proband or in family history; (4) reduced penetrance and clinical variability should be considered to deliver appropriate genetic counseling. PMID- 27280172 TI - An Organocobalt-Carbon Nanotube Chemiresistive Carbon Monoxide Detector. AB - A chemiresistive detector for carbon monoxide was created from single-walled carbon nanotubes (SWCNTs) by noncovalent modification with diiodo(eta5: eta1-1-[2 (N,N-dimethylamino)ethyl]-2,3,4,5-tetramethylcyclopentadienyl)-cobalt(III) ([Cp^CoI2]), an organocobalt complex with an intramolecular amino ligand coordinated to the metal center that is displaced upon CO binding. The unbound amino group can subsequently be transduced chemiresistively by the SWCNT network. The resulting device was shown to have a ppm-level limit of detection and unprecedented selectivity for CO gas among CNT-based chemiresistors. This work, the first molecular-level mechanistic elucidation for a CNT-based chemiresistive detector for CO, demonstrates the efficacy of using an analyte's reactivity to produce another chemical moiety that is readily transduced as a strategy for the rational design of chemiresistive CNT-based detectors. PMID- 27280174 TI - Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection. AB - Point of care molecular diagnostics benefits from a portable battery-operated device capable of performing a fast turnaround using reliable inexpensive cartridges. We describe a prototype device for performing a molecular diagnostics test for clinical and biodefense samples in 16 minutes using a prototype capable of an 8 minute PCR reaction, followed by hybridization and detection on an electrochemical microarray based on the i-STAT(r) system. We used human buccal swabs for hemochromatosis testing including in-device DNA extraction. Additional clinical and biodefense samples included influenza A and bacterial select agents Bacillus anthracis, Yersinia pestis and Francisella tularensis. PMID- 27280173 TI - Quantitative podocyte parameters predict human native kidney and allograft half lives. AB - BACKGROUND: Kidney function decreases with age. A potential mechanistic explanation for kidney and allograft half-life has evolved through the realization that linear reduction in glomerular podocyte density could drive progressive glomerulosclerosis to impact both native kidney and allograft half lives. METHODS: Predictions from podometrics (quantitation of podocyte parameters) were tested using independent pathologic, functional, and outcome data for native kidneys and allografts derived from published reports and large registries. RESULTS: With age, native kidneys exponentially develop glomerulosclerosis, reduced renal function, and end-stage kidney disease, projecting a finite average kidney life span. The slope of allograft failure rate versus age parallels that of reduction in podocyte density versus age. Quantitative modeling projects allograft half-life at any donor age, and rate of podocyte detachment parallels the observed allograft loss rate. CONCLUSION: Native kidneys are designed to have a limited average life span of about 100-140 years. Allografts undergo an accelerated aging-like process that accounts for their unexpectedly short half-life (about 15 years), the observation that older donor age is associated with shorter allograft half-life, and the fact that long term allograft survival has not substantially improved. Podometrics provides potential readouts for these processes, thereby offering new approaches for monitoring and intervention. FUNDING: National Institutes of Health. PMID- 27280175 TI - Nanocrystals in compression: unexpected structural phase transition and amorphization due to surface impurities. AB - We report an unprecedented surface doping-driven anomaly in the compression behaviors of nanocrystals demonstrating that the change of surface chemistry can lead to an interior bulk structure change in nanoparticles. In the synchrotron based X-ray diffraction experiments, titania nanocrystals with low concentration yttrium dopants at the surface are found to be less compressible than undoped titania nanocrystals. More surprisingly, an unexpected TiO2(ii) phase (alpha-PbO2 type) is induced and obvious anisotropy is observed in the compression of yttrium doped TiO2, in sharp contrast to the compression behavior of undoped TiO2. In addition, the undoped brookite nanocrystals remain with the same structure up to 30 GPa, whereas the yttrium-doped brookite amorphizes above 20 GPa. The abnormal structural evolution observed in yttrium-doped TiO2 does not agree with the reported phase stability of nano titania polymorphs, thus suggesting that the physical properties of the interior of nanocrystals can be controlled by the surface, providing an unconventional and new degree of freedom in search for nanocrystals with novel tunable properties that can trigger applications in multiple areas of industry and provoke more related basic science research. PMID- 27280176 TI - Molecular properties of aqueous solutions: a focus on the collective dynamics of hydration water. AB - When a solute is dissolved in water, their mutual interactions determine the molecular properties of the solute on one hand, and the structure and dynamics of the surrounding water particles (the so-called hydration water) on the other. The very existence of soft matter and its peculiar properties are largely due to the wide variety of possible water-solute interactions. In this context, water is not an inert medium but rather an active component, and hydration water plays a crucial role in determining the structure, stability, dynamics, and function of matter. This review focuses on the collective dynamics of hydration water in terms of retardation with respect to the bulk, and of the number of molecules whose dynamics is perturbed. Since water environments are in a dynamic equilibrium, with molecules continuously exchanging from around the solute towards the bulk and vice versa, we examine the ability of different techniques to measure the water dynamics on the basis of the explored time scales and exchange rates. Special emphasis is given to the collective dynamics probed by extended depolarized light scattering and we discuss whether and to what extent the results obtained in aqueous solutions of small molecules can be extrapolated to the case of large biomacromolecules. In fact, recent experiments performed on solutions of increasing complexity clearly indicate that a reductionist approach is not adequate to describe their collective dynamics. We conclude this review by presenting current ideas that are being developed to describe the dynamics of water interacting with macromolecules. PMID- 27280177 TI - Nanoporous gold leaf as a signal amplification agent for the detection of VOCs with a quartz crystal microbalance. AB - In this work, a novel sensing framework coupling nanoporous gold leaf (NPGL) and sensitive materials on a quartz crystal microbalance (QCM) sensor was developed for the detection of volatile organic compounds (VOCs). A bi-layer structure was established through a two-step modification process, where NPGL served as a loading platform to anchor more sensitive materials and provide a larger surface area. Sensitive materials for different target analytes (ethanol, benzene and n heptane) were optimized, as well as the selection of the most suitable NPGL. The morphology of the bi-layer was characterized and the sensing performance, including the detection range, response time, reversibility, stability, etc., was investigated. The thermodynamics and kinetics of the gas adsorption process were studied by employing several classical models. It was found that the adsorption of the tested VOCs was more accurately represented using the Freundlich isotherm and the adsorption kinetics of these VOCs fitted well with pseudo second-order kinetics. The results of on-line monitoring demonstrated admirable sensing properties, fully indicating that the QCM sensor modified with a composite layer of sensitive material/NPGL has promising application prospects for real-time detection. PMID- 27280178 TI - Retraction notice to: Pink tooth phenomenon: An enigma? [J Forensic Leg Med 20(7) (October 2013) 912-914]. PMID- 27280179 TI - Spironolactone is the Most Effective "add-on" Medication For Resistant Hypertension. PMID- 27280180 TI - Poor Choices of Antihypertensive Drugs. PMID- 27280181 TI - Home Monitoring in the US: Its About Time. PMID- 27280182 TI - Physical health passports for patients with severe and enduring mental illness. PMID- 27280183 TI - Robert Spitzer: the most influential psychiatrist of his time. PMID- 27280184 TI - In memory. Dr. Norman McSwain Jr. PMID- 27280185 TI - Special talk: an interview. MSG Harold "Monty" Montgomery on a career as a special operations forces medic. PMID- 27280186 TI - TCCC updates. Tactic combat casualty care guidelines for medical personnel: 3 June 2015. PMID- 27280187 TI - TacMed updates. The Committee for Tactical Emergency Casualty Care: fall update. PMID- 27280188 TI - Effects of Hexane in Supercritical Fluid Chromatography for the Separation of Enantiomers. AB - Supercritical fluid chromatography (SFC), operated in conventional mode, is normally recognized as normal phase chromatography, and uses a solvent combination of supercritical CO2 and alcohols to separate compounds. Hexane, a commonly used solvent in normal phase liquid chromatography (NP-LC), is rarely used in SFC and, in some cases, is added to the organic modifiers to increase liquid content in order to achieve better efficiency in preparative SFC for poorly retained compounds. Although hexane is believed to have similar solvent strength to that of supercritical CO2, its effects on the enantioseparation in SFC is largely unknown. To understand the chromatographic effects of an apolar solvent, such as hexane in SFC, we compared the chromatographic behaviors of 35 chiral compounds using a parallel SFC method under traditional SFC mode of only "pure" alcohol-CO2 to that of hexane-assisted SFC (HA-SFC), which uses mixtures of alcohol and hexane (as cosolvents) and CO2. We observed that, in some cases, hexane behaves just like supercritical CO2, where replacement of a portion of CO2 with hexane does not significantly change retention times or resolution of the peaks. In many cases, however, addition of hexane in mobile phases does affect chromatographic behavior of one or both enantiomers. Such effects might provide opportunities for separation of some enantiomers. PMID- 27280189 TI - Wait Time for Biosimilar Regs Drags On. PMID- 27280190 TI - Muscular Dystrophy Drug Could Pave Way for RNA Medications. PMID- 27280191 TI - SECURITY STARTS AT ENCRYPTION. Organizations step up data defense efforts. PMID- 27280192 TI - CAN EHRs KEEP PACE? New demands lead to system innovations. PMID- 27280193 TI - Intense pharma lobbying in the EU. PMID- 27280197 TI - COMMON STEM--setron. PMID- 27280198 TI - Drug-induced hair loss. AB - Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes. PMID- 27280199 TI - Ondansetron and pregnancy: possible congenital heart defects. AB - Two cohort studies, including more than 2500 pregnant women exposed to ondansetron in early pregnancy, have raised concerns over an increased risk of congenital heart defects. PMID- 27280200 TI - Olmesartan: sprue-like enteropathy. AB - A cohort study conducted in 2014, using data from France's mandatory health insurance system, has shown a 10-fold increased risk of hospitalisation for enteropathy with olmesartan in comparison with other ARBs (sartans) or ACE inhibitors. The increased incidence of enteropathy with olmesartan compared with other ARBs or ACE inhibitors is well documented. The French drug regulatory agency, ANSM, informed healthcare professionals of these risks in 2014. Yet prescription rates for olmesartan remain high, and new cases of olmesartan associated enteropathy continue to be reported. Patients would be better served if health professionals stopped using olmesartan and regulators withdrew this drug from the market. PMID- 27280205 TI - Aphrodite and her sisters. PMID- 27280206 TI - Nordic Noir: Fact, fiction, fetish, fantasy. PMID- 27280207 TI - Early, Funny - Stardust Memories. PMID- 27280208 TI - What difference should International Nurses Day make? PMID- 27280209 TI - Sexual expression in nursing homes: a neglected nursing ethics issue. PMID- 27280210 TI - Contrasting Schwartz Rounds with clinical ethics: three perspectives on their potential to impact on end-of-life care. PMID- 27280211 TI - Testing of Junctional Tourniquets by Military Medics to Control Simulated Groin Hemorrhage. PMID- 27280213 TI - From the SEMA. PMID- 27280212 TI - Author Reply. PMID- 27280214 TI - From the SOMA PRESIDENT. PMID- 27280215 TI - Steve Rush on US Air Force Pararescue and Pararesuemen today. PMID- 27280216 TI - From the PUBLISHER. PMID- 27280217 TI - Providers face challenges maintaining deployment-ready skills at Garrison hospitals. PMID- 27280218 TI - "Rationale for use of intravenous acetaminophen in Special Operations medicine.". PMID- 27280219 TI - Reply. PMID- 27280220 TI - Frank Butler on serving the operational medicine community. PMID- 27280221 TI - Stop the bleed. Strategies to enhance survival in active shooter and intentional mass casualty events. The Hartford Consensus. A major step forward in translating battlefield trauma care advances to the civilian sector. PMID- 27280222 TI - The Hartford Consensus III. Implementation of bleeding control. PMID- 27280223 TI - The continuing threat of active shooter and intentional mass casualty events. Local and law enforcement and hemorrhage control. PMID- 27280224 TI - Building community resilience to dynamic mass casualty incidents: a multiagency white paper in support of the first care provider. PMID- 27280225 TI - Train to failure. MSG Dennis Lyons of USASOC on medical training and learning. PMID- 27280226 TI - Summaries for Patients. Acupuncture for Treatment of Menopausal Hot Flashes. PMID- 27280227 TI - Animal extremists' threats to neurologic research continue: Neuroreality II. PMID- 27280228 TI - Animal extremists' threats to neurologic research continue: Neuroreality II. PMID- 27280229 TI - Author Response. PMID- 27280230 TI - A "Red Flag" in Patients with Sickle cell anaemia. PMID- 27280231 TI - Liver aminotransferases in under-five HIV-positive children on HAART. AB - BACKGROUND: Higher mortality rates were reported in developing countries during early months of HAART initiation than in developed countries. The study aimed at assessing the effect of Highly Active Antiretroviral Therapy (HAART) on liver function of under-fives. METHOD: Two hundred and thirty-eight under-fives children were enrolled from five hospitals in Southern Nigeria. Ethical permission and written consent were obtained. Group A involved 91 seropositive children on HAART regimen while Group B1 involved 24 seronegative-infants who received nevirapine from birth till age 6-week. Group B2 (18) and B3 (48) involved seronegative-children who received co-trimoxazole and were 6-month and 18-month old respectively. Group C involved 11 seropositive-children who received co-trimoxazole only. Group D involved 46 seronegative-children who served as the control group. A 2ml blood sample was obtained from each participant during first phase of the study and was analysed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) using kits manufactured by Randox. Group A children returned for second and third phases of the study after 3-month and 6 month respectively. Data were analysed by using ANOVA. RESULTS: The results showed that ALT was highest in group A (12.8 +/- 11.0 IU/L) suggesting hepatotoxicity while AST was highest in group B2 (35.4 +/- 53.1 IU/L). Second phase, ALT and AST of group A were significantly reduced by 39.3% (p < 0.05), 29.9% (p < 0.05) respectively suggesting resolved hepatotoxicity. Third phase, ALT and AST were significantly reduced by .50.6% (p < 0.05) and 32.2% (p < 0.05) respectively suggesting resolved hepatotoxicity. CONCLUSION: Hepatotoxicity observed among HIV-infected children on HAART was resolved after 6-month of monitoring. PMID- 27280232 TI - Perception and attitude towards Ebola Virus Disease among traditional healers in Ibadan, Nigeria. AB - BACKGROUND: Nigeria experienced her first outbreak of Ebola Virus Disease (EVD) in the second-half of 2014. Since its first occurrence in Zaire and Sudan in 1976, most studies on EVD were clinically based and were carried out using biomedical approaches. No empirical social science/behavioural-oriented study exists on the deadly EVD in Nigeria. OBJECTIVE: This study examined the traditional healers' perception and attitude towards Ebola virus disease in Ibadan metropolis. STUDY DESIGN: Purposive sampling method was used to select a total of 23 traditional healers who specialized in different areas of traditional medicine (such as herbs selling, faith healing, divination, and general practice). In-depth interview (IDI) method was employed in the study. RESULTS: The study found some misconceptions about the disease while the dominant attitude among the healers was that of avoidance and caution on safety. CONCLUSION: The healers' interpretations of the disease rested on the culture and individual experiences. There is thus a need to take the local cultural perceptions of the Ebola Virus Disease into consideration when controlling the disease in the future. PMID- 27280233 TI - Non cholinergic dependent mechanism of Ocimum gratissimum induced neurobehavioural alterations in mice. AB - BACKGROUND: This study investigated the mechanism of Ocimum gratissimum induced neurobehavioural alterations in mice. The plant is widely consumed in most parts of the world including Nigeria where it is used as a spice and phytomedicine by alternate medical practitioners. METHODS: The animals were divided into three groups of six mice each. Control and Ocimum gratissum treated mice were subjected to the hole-board, light/dark box, elevated plus maze and open field tests. The third group had an intraperitoneal (i.p) injection of the cholinergic receptor antagonist, atropine (3 mg/kg) forty-five minutes prior to oral Ocimum gratissimum administration before the neurobehavioural assay one hour later. RESULTS: The results showed that Ocimum gratissimum administration significantly reduced the number of head dips in the hole board test (p < 0.01), so also were the frequencies of locomotion (p < 0.001), rearing (p < 0.05) and grooming (p < 0.01) compared with control. In the light/dark board test, the time spent in the light arena and the number of entries were significantly (p < 0.001) reduced compared with the control, while in the elevated plus maize test, the time spent in the closed arm increased significantly (p < 0.01) when compared with control values. The values obtained when the animals were pre-treated with atropine (3 mg/kg) before the administration of Ocimum gratissimum showed no significant difference from those observed without the cholinergic blocker in all the four neurobehavioural tests. CONCLUSION: These results ruled out any significant participation of the cholinergic system in Ocimum gratissimum induced neurobehavioural alterations in mice. PMID- 27280234 TI - Microwave disinfection of maxillary and mandibular denture bases contaminated with Candida Albican. AB - BACKGROUND: Oral environment is not sterile, and dentures worn by the patients can be infected and therefore needs disinfection. Solution disinfectants such as sodium hypochlorite and glutaraldehyde can be used but they have side effects. Microwave disinfection method is more recent, however, there are conflicting reports at the moment on the appropriate power and time regimen for disinfection of denture. OBJECTIVE: To determine the power and time regimen at which the disinfection of dentures can be achieved using microwave. METHOD: Forty-five acrylic denture bases were fabricated for each of the jaws and infected with solution of a stock Candida albicans and 30 infected bases were employed as control. These were placed in normal saline and then subjected to different microwave power and time regimen. Aliquots from these post-microwave solution were titrated against sabauraud agar which was subsequently incubated at 37 degrees C for 48 hours. The agar were examined for candida growth. RESULT: The denture bases subjected to microwave disinfection at 350W showed Candida growth after microwave treatment irrespective of the time employed. Conversely, those microwaved at 650W and 690W for four and six minutes showed no microbial growth. CONCLUSION: The microwave regimen of 650W at 4 and 6 minutes completely disinfected the denture bases. Disinfection at higher microwave energy should be done with caution as distortion of the denture may occur. PMID- 27280236 TI - Refractive Amblyopia among children in Ibadan: the need for amblyopia screening programmes. AB - BACKGROUND: The prevalence and burden of amblyopia in developing countries is probably underestimated, and little is known about the pattern of amblyopia in West Africa. AIM: To determine the relative frequency and types of amblyopia among children with refractive errors seen in the eye clinic of a tertiary hospital over a 2 year period. METHODS: A cross-sectional study conducted at the eye clinic of the University College Hospital, Ibadan, Nigeria between January 2012 and December 2013. Case notes of children with refractive errors seen during this period were retrieved and information including socio-demographic data, presenting visual acuity and visual acuity with correction were recorded. Amblyopia was defined as best corrected visual acuity worse than 6/9 or a difference of >= 2 Snellen chart lines between both eyes in the absence of any ocular pathology that could explain the visual impairment. RESULTS: A total of 250 eligible patients who had refractive errors were included in the study. Visual acuity was corrected to 6/9 or better in 224 (89.6%) children while 26 (10.4%) of them had amblyopia. Among the 26 children with amblyopia, 21 (80.8%) children had amblyopia in both eyes and majority (65.4%) had iso-ametropic amblyopia. Of the 47 amblyopic eyes, 36 (76.6%) eyes had moderate amblyopia while 11 (23.4%) eyes had severe amblyopia. CONCLUSION: There is a high relative frequency of amblyopia in this study and we recommend preschool eye examinations for all children to ensure early detection and management of amblyopia, thereby reducing the burden of amblyopia in our populace. PMID- 27280235 TI - Effect of taurine and caffeine on plasma c-reactive protein and calcium in Wistar rats. AB - BACKGROUND: Caffeine is a component of several beverages such as coffee and tea. It has been shown to possess psychoactive properties because it increases alertness, energy and ability to concentrate at moderate doses. Taurine on the other hand, is an amino acid which has the capacity to promote neural development, osmoregulation and neuroprotection. There is paucity of information on the effect of the combined administration of taurine and caffeine on C reactive protein (CRP)--a marker of inflammation and plasma calcium level in rats. AIM: The present study was designed to investigate the effects of combined taurine and caffeine on the plasma level of CRP, Ca2+ as well as the effect of nifedipine on calcium level. METHOD: Fifty four rats weighing 120-140 g were used for these studies. The animals were divided into nine groups consisting of six animals each. Group 1 was treated with 10 m/kg of normal saline, Groups 2 and 3 were given 100 mg/kg and 200 mg/kg of taurine respectively, groups 4 and 5 received 7.5 mg/kg and 15 mg/kg of caffeine respectively while group 6 was administered taurine (200 mg/kg) and caffeine (15 mg/kg), groups 7 and 8 were treated with taurine (200 mg/kg) plus nifedipine (10 mg/kg) and taurine (200 mg/kg)plus furosemide (20 mg/kg) respectively while group 9 was given taurine plu caffeine plus nifdipine plus furosemide. Treatment was done once daily for 21 days and blood was finally collected via cardiac puncture for the assay of CRP and calcium while the animals were under anaesthesia. RESULTS: The results showed that CRP was significantly decreased in five of the treated groups compared with the control with the exception of the group treated with taurine alone (Group 2), and that treated with combined taurine and caffeine (Group 6). The Ca2+ level of groups treated with caffeine (11.70 +/- 0.29 mg/dL) and taurine with caffeine (11.64 +/- 0.15 mg/dL) were significantly (p < 0.05) increased compared with the control (10.70 +/- 0.29 mg/dL). However, treatment with taurine and nifedipine (Group 7) led to significant (p < 0.05) reduction in plasma Ca2+ level. CONCLUSION: The results have shown that combined caffeine and taurine can boost plasma calcium level and decrease plasma CRP level. Moreover, taurine combined with nifedipine but not furosemide can act synergistically to lower both plasma Ca2+ and CRP levels, a result which may have implication for the treatment of hypertension. PMID- 27280237 TI - Predictors of hypoxaemia during steady-state among children with Sickle Cell Anaemia in North-Western Nigeria. AB - Abstract BACKGROUND: Haemoglobin desaturation, which presents as hypoxaemia, is a known phenomenon in the cycle of red blood cells sickling in sickle cell anaemia (SCA). Thus, early and accurate recognition of hypoxaemia is important in order to ameliorate its adverse effects on vital organs. This study was carried out to investigate clinical and laboratory features that predict hypoxaemia in children with SCA during steady-state. METHODS: We prospectively measured percutaneous haemoglobin saturation of 208 children with SCA in room air during steady-state at a secondary health facility in the north-west of Nigeria. Demographic, clinical and laboratory features and anthropometry were recorded. Hypoxaemia was defined as haemoglobin saturation < 90%. Chi square test and logistic regression were used to assess the associations of selected factors with hypoxaemia. RESULTS: Participants comprised 132 males and 76 females and their age ranged from 9 to 168 months. Prevalence of hypoxaemia was 17.3%. Though hypoxaemia was significantly associated with age, time of first symptom to presentation, body mass index (BMI), weight-for-height z-score < 2.0, tachycardia, chest retraction and palpable spleen, age (OR = 0.78; 95% CI = 0.62, 0.96), time of first symptom to presentation (OR = 1.28; 95% = 1.03, 1.59), BMI (OR = 0.87; 95% = 0.76, 0.92) and palpable spleen (OR = 2.87; 95% CI = 1.43, 16.65) remained independent predictors in the logistic regression model. CONCLUSION: Careful consideration should be given to time of first symptom to presentation, body mass index and palpable spleen when evaluating children with sickle cell anaemia for hypoxaemia in resource limited settings. PMID- 27280238 TI - Evaluation of anti-ulcerogenic and ulcer-healing activities of nevirapine in rats. AB - BACKGROUND: Nevirapine is a very potent antiretroviral drug frequently used in the management of Human Immunodeficiency Virus (HIV). Opportunistic pathologies in HIV/AIDS patients include gastric ulcer and gastrointestinal haemorrhage. Hence, the impact of nevirapine on induced gastric ulcer was studied using Wistar rats. METHODS: Anti-ulcer activity of nevirapine was evaluated using cold restraint stress-induced, ethanol-induced and pylorus ligation-induced gastric ulcer models for acute ulceration; and acetic acid-induced ulcer model for the chronic ulceration in Wistar rats. RESULTS: Nevirapine (9 mg/kg, 18 mg/kg and 36 mg/kg) showed significant (P < 0.05) reduction in ulcer severity score and ulcer index as compared to the control in the models,.with corresponding increase in percentage inhibition. Histopathological studies showed that nevirapine has a positive effect on the healing of gastric ulcer in the groups treated with the nevirapine compared with the control. The induced ulcers healed up in all the groups administered with nevirapine compared to what was found in the omeprazole group where manifestations of ulcer like inflammatory cells infiltration is still present. CONCLUSION: Nevirapine may possess highly therapeutic effect in the treatment and prevention of gastrointestinal complications that might come with the presence of HIV virus in patients. PMID- 27280239 TI - Effect of methanol extract of musa sapientum leaves on protein glycation and erythrocyte antioxidant status in alloxan-induced diabetic Wistar rats. AB - BACKGROUND: Increased generation of free radicals from protein glycation has been associated with compromised integrity of erythrocytes in diabetes. Musa sapientum has been reported to possess anti-diabetic properties and this study investigated the effect of methanol extract of Musa sapientum on protein glycation and erythrocyte integrity. METHODS: Forty-two male Wistar rats (180-200g) were randomly grouped into seven: 1 (control), 2 (diabetic untreated), 3 (normal extract-treated (250 mg/kg)), 4 (normal metformin-treated (150 mg/kg)), 5 (diabetic extract-treated (250 mg/kg)), 6 (diabetic metformin-treated (150 mg/kg)), 7 (diabetic insulin-treated (1 IU/kg)). Diabetes was induced with single intraperitoneal injection of 120 mg/kg alloxan. Animals were treated for 14 days and blood (3 mls) was collected from retro-orbital plexus to determine serum fructosamine level, erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Glycated haemoglobin (HbA(1c)) level was estimated using a conversion formula. Animals were sacrificed thereafter by cervical dislocation and pancreatic tissues were excised and stained with haematoxylin and eosin for histological study. Statistical significance at P < 0.05 was analyzed by one-way ANOVA and Newman-Keuls' post-hoc test. RESULTS: Diabetic rats treated with extract, metformin and insulin had significant reduction in serum fructosamine level by 62.64%, 74.63% and 56.05% respectively while HbA(1c) level reduced by 45.06%, 50.62% and 40.57% respectively. Activities of erythrocyte SOD and GPx were increased in the extract-treated group. Histological studies showed regeneration of islet cells in the diabetic extract-treated rat which was comparable to normal. CONCLUSION: The extract inhibited protein glycation, regenerated the islet cells and improved erythrocyte antioxidant status in diabetic rats. PMID- 27280240 TI - Pharmaceutical equivalent studies of some commercially available brands of Loratadine hydrochloride tablets. AB - BACKGROUND: This study was undertaken with the objective of evaluating the pharmaceutical and chemical equivalence of some commercially available loratadine tablets, and offers a possible explanation for the therapeutic failure of the drug products. METHOD: The equivalence of eight brands of loratadine hydrochloride tablets labelled A to H was assessed and compared with the Innovator brand labelled I. Visual observation and uniformity of weight tests were carried out on the tablets, mechanical properties were assessed using friability and crushing strength tests as parameters. Release properties of the tablets were assessed by disintegration and dissolution tests. Assay was based on non-aqueous titration procedure using crystal violet solution indicator. RESULT: All the brands studied were white in colour with different shapes and lustre, and complied with the official specification for uniformity of tablet weight. Friability tests showed that only brand G lost more than 1% of its initial weight, while brands A and E failed the crushing strength test. Brand C did not undergo complete disintegration within 15 minutes, while brands A, B, F and G had less than 70% of the active drug content still in solution after 45 minutes. Two of the brands had active drug content between officially specified range of 98.5% and 101.5% for loratadine tablets. CONCLUSION: There was a large variation in the pharmaceutical properties of the commercially available loratadine hydrochloride tablets that were selected for this study. Six of the brands evaluated exhibited poor pharmaceutical properties. Generally, only two of the brands were pharmaceutically equivalent with the innovator brand. PMID- 27280241 TI - Non-operative treatment of neglected bilateral posterior four-part fracture- dislocation of the shoulders--a case report. AB - BACKGROUND: Bilateral posterior dislocation of the shoulders is rare and may result from a seizure. A 48 year-old HIV-positive man who presented eight weeks after bilateral posterior shoulder dislocation and bilateral fractures of the surgical necks of both humeri is reviewed. He was treated with an algesics and physiotherapy and was able to return to work after 9 months. CONCLUSION: The rarity of this lesion, its late presentation, the importance of a high index of suspicion in making the diagnosis and the fair outcome of non-operative treatment informed this report. PMID- 27280242 TI - Modulation of Dendritic Cells by Nanotechnology-Based Immunotherapeutic Strategies. AB - In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking immune tolerance. Immunotherapy has been, for the last two decades, an attractive and promising therapeutic approach to fight cancer. This review will approach the nature of the immune response during cancer development and its correlation with DC function, as well as cancer vaccine principles and limitations. An overview of several delivery strategies used for in vivo modulation of DCs and direct activation of T cells will be provided, highlighting their advantages, limitations, and optimization strategies. This manuscript also presents a critical and systematic review of recent clinical trials that are investigating the therapeutic effect of these approaches, discussing prognostic outcomes of combined-treatment modalities. PMID- 27280243 TI - Chemotherapeutic Evaluation of Guar Gum Coated Chitosan Nanoparticle Against Experimental Tuberculosis. AB - The major goal of the current research was to develop and evaluate the therapeutic potential of anti-tubercular drugs (ATDs) loaded natural polysaccharide comprising of galacto mannan subunit in experimental tuberculosis (TB). Experimental formulations were prepared by ionotropic gelation technique followed by spray drying. Morphological analysis suggested that optimized nanoparticles were found to be discrete and spherical in nature with a particle size distribution range from 230 +/- 4.5 nm to 310 +/- 6.2 nm. The in-vitro drug release behavior indicated the biphasic pattern comprising of initial burst followed by a sustained release pattern. Guar gum coated chitosan nanoparticles (CGNPs) among the leading formulation exhibited the highest cell uptake potential confirmed by FACS analysis. Challenge study also supports the in-vivo bio distribution illustrated by the significant reduction in CFU count in experimental TB in mice. Histopathology study demonstrated that none of the treated group shows any evidence of lung tissue abnormality. Hence, the study marked the fact that CGNPs could be a promising carrier for selective delivery of ATDs to alveolar macrophages for efficient management of TB with the interception of minimal side effects. PMID- 27280244 TI - Quantitative 3D Determination of Radiosensitization by Bismuth-Based Nanoparticles. AB - The nanoparticle-induced dose enhancement effect has been shown to improve the therapeutic efficacy of ionizing radiation in external beam radiotherapy. Whereas previous studies have focused on gold nanoparticles (AuNPs), no quantitative studies have been conducted to investigate the potential superiority of other high atomic number (Z) nanomaterials such as bismuth-based nanoparticles. The aims of this study were to experimentally validate and quantify the dose enhancement properties of commercially available bismuth-based nanoparticles (bismuth oxide (Bi2O3-NPs) and bismuth sulfide (Bi2S3-NPs)), and investigate their potential superiority over AuNPs in terms of radiation dose enhancement. Phantom cuvettes doped with and without nanoparticles where employed for measuring radiation dose enhancement produced from the interaction of radiation with metal nanoparticles. Novel 3D phantoms were employed to investigate the 3D spatial distribution of ionising radiation dose deposition. The phantoms were irradiated with kilovoltage and megavoltage X-ray beams and optical absorption changes were measured using a spectrophotometer and optical CT scanner. The radiation dose enhancement factors (DEFs) obtained for 50 nm diameter Bi2O3-NPs and AuNPs were 1.90 and 1.77, respectively, for 100 kV energy and a nanoparticle concentration of 0.5 mM. In addition, the DEFs of 5 nm diameter Bi2S3-NPs and AuNPs were determined to be 1.38 and 1.51, respectively, for 150 kV energy and a nanoparticle concentration of 0.25 mM. The results demonstrate that both bismuth based nanoparticles can enhance the effects of radiation. For 6 MV energy the DEFs for all the investigated nanoparticles were lower (< 15%) than with kilovoltage energy. PMID- 27280245 TI - Estimation of Biocompatibility of Nano-Sized Ceramic Particles with Osteoblasts, Osteosarcomas and Hepatocytes by Static and Time-Lapse Observation. AB - We assessed the biocompatibility of nano-sized ceramic particles with several cells types. Though these particles have less than 100 nm in diameter, they act as submicron-sized particles in saline by aggregation that was estimated using laser diffraction particle size analysis (LDS). they act as submicro-sized particles in saline by aggregation based on laser diffraction particle size analysis (LDS). Several types of cells (osteoblasts, osteosarcoma and hepatocyte cells) were exposed to these particles and their cytocompatibility was estimated. Not only the cytotoxic assay but also their static and dynamic morphology under nanoparticles exposure were investigated. The intercellular uptake of particles was determined using a confocal fluorescence microscope. The particles used in this study did not inhibit cellular activity or growth even when their concentrations were high. Only copper oxide particles caused acute cytotoxicity depending on the particle size. The cytotoxicity assay, dynamic behavior of the nanoparticle-exposed cells and their examination under a confocal fluorescence microscope suggests that the irritative reaction was induced by contact between the cells and particles, whereas eluted copper ions are not dominant factor. These results indicate that nano-sized particles used in this study have excellent biocompatibility except copper oxide ones. PMID- 27280246 TI - Application of Gold Nanorods for Photothermal Therapy in Ex Vivo Human Oesophagogastric Adenocarcinoma. AB - Gold nanoparticles are chemically fabricated and tuned to strongly absorb near infrared (NIR) light, enabling deep optical penetration and therapy within human tissues, where sufficient heating induces tumour necrosis. In our studies we aim to establish the optimal gold nanorod (GNR) concentration and laser power for inducing hyperthermic effects in tissues and test this photothermal effect on ex vivo human oesophagogastric adenocarcinoma. The ideal GNR concentration and NIR laser power that would elicit sufficient hyperthermia for tumour necrosis was pre determined on porcine oesophageal tissues. Human ex vivo oesophageal and gastric adenocarcinoma tissues were incubated with GNR solutions and a GNR-free control solution with corresponding healthy tissues for comparison, then irradiated with NIR light for 10 minutes. Temperature rise was found to vary linearly with both the concentration of GNRs and the laser power. Human ex vivo oesophageal and gastric tissues consistently demonstrated a significant temperature rise when incubated in an optimally concentrated GNR solution (3 x 10(10) GNRs/ml) prior to NIR irradiation delivered at an optimal power (2 W/cm2). A mean temperature rise of 27 degrees C was observed in tissues incubated with GNRs, whereas only a modest 2 degrees C rise in tissues not exposed to any GNRs. This study evaluates the photothermal effects of GNRs on oesophagogastric tissue examines their application in the minimally invasive therapeutics of oesophageal and gastric adenocarcinomas. This could potentially be an effective method of clinically inducing irreversible oesophagogastric tumour photodestruction, with minimal collateral damage expected in (healthy) tissues free from GNRs. PMID- 27280247 TI - Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer. AB - Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA. PMID- 27280248 TI - Glutathione-Responsive Multilayer Coated Gold Nanoparticles for Targeted Gene Delivery. AB - Efficient gene release after intracellular uptake is very important for non-viral gene delivery systems. To construct a glutathione-responsive gene delivery system, we developed gold-cysteamine (AuCM)/plasmid DNA (pDNA)/poly TAT (pTAT)/hyaluronic acid (HA) nanocomplexes (AuCM/pDNA/pTAT/HA) in this study. The AuCM/pDNA/pTAT/HA nanocomplexes possessed a small size less than 200 nm and negative zeta potential of -17 +/- 4 mV. The multilayer structure was verified by UV-Vis spectra, surface charges, dynamic light scattering. Morphology was observed by transmission electron microscope. The AuCM/pDNA/pTAT/HA nanocomplexes could completely protect pDNA against enzymatic degradation. These nanocomplexes showed effective cellular uptake in CD44 receptors over-expressed HepG 2 cells in a HA/CD44 interaction dependent manner. Moreover, transfection efficacy was significantly enhanced in AuCM/pDNA/pTAT/HA treated HepG 2 cells compared with AuCM/pDNA/pTAT, and was further enhanced in the presence of GSH, indicating that AuCM/pDNA/pTAT/HA was glutathione-responsive. Biodistribution revealed that AuCM/pDNA/pTAT/HA nanocomplexes mainly accumulated in liver. In conclusion, AuCM/pDNA/pTAT/HA nanocomplexes may serve as glutathione-responsive gene carriers for actively targeting gene delivery to CD44 receptors over-expressed liver cancers. PMID- 27280249 TI - A Novel Microbubble Capable of Ultrasound-Triggered Release of Drug-Loaded Nanoparticles. AB - Drug-loaded microbubbles have shown attractive potential in disease treatment applications. The present work presents a unique ultrasound (US)-triggered system in which drug-loaded nanoparticles and perfluorocarbon gas are encapsulated within the internal space of microbubbles. The prepared curcumin-loaded albumin nanoparticle payload microbubbles (CcmANP-MB) exhibited a mean diameter of 4895.1 nm +/- 421.2 nm and a drug-loading efficiency of 2.23% +/- 0.08% (297% increase compared with the drug loading of common drug-loaded microbubbles). US allowed the release of the internal payload. In vitro US-triggered drug release experiments showed that the drug release of CcmANP-MB was delayed by lipid membranes and significantly increased after sonication. In vitro and in vivo US imaging experiments demonstrated that CcmANP-MB evidently enhances US imaging, which indicates that the microbubbles possess good acoustic properties even after encapsulation of nanoparticles. Tumor bearing mice were administered with CcmANP MB through the tail vein and were then exposed to ultrasound, which resulted in an enhanced drug accumulation in tumor tissues and a significant increase in tumor growth inhibition rate (57.1%) compared with CcmANP-MB alone (28.8%) as well as curcumin-loaded albumin nanoparticle (26.2%). Therefore, the combination of lecithin microbubbles and albumin nanoparticles provides a platform for targeted drug delivery in clinical therapy and disease diagnosis. PMID- 27280250 TI - In Vitro Effect of 30 nm Silver Nanoparticles on Adipogenic Differentiation of Human Mesenchymal Stem Cells. AB - With the combined use of silver nanoparticles (Ag NPs) and human bone marrow derived mesenchymal stem cells (hMSCs) in bone tissue engineering, more knowledge of the effects of Ag NPs on hMSCs is required. Up to date, researches mainly focused on the cytotoxicity and genotoxicity of Ag NPs, only few studies discussed their influence on the differentiation of stem cells, especially adipogenic differentiation. In the present study, we investigated the in vitro uptake of 30 nm PVP-coated Ag NPs in hMSCs and their effects on cell viability, cell morphology and adipogenic differentiation of hMSCs. HMSCs were exposed to Ag NPs at concentrations of 25 and 50 MUg/mL for 24 hours and at concentrations of 5 and 10 MUg/mL throughout the whole differentiation period. Results of cell viability showed that Ag NPs caused time- and dose-dependent toxicity in hMSCs. Transmission electron microscopy (TEM) confirmed the uptake of Ag NPs into cytoplasm of hMSCs. No influence on cell morphology was observed. The 30 nm sized Ag NPs had no effects on adiponectin secretion, lipid droplet formation and the expression of adipogenic marker genes. It is concluded that under our experimental conditions, 30 nm PVP-coated Ag NPs do not influence the adipogenic differentiation of hMSCs in vitro. The present results provide a reference for the usage of 30 nm Ag NPs in the presence of hMSCs in bone tissue engineering. PMID- 27280251 TI - Size-Dependent Cellular Uptake of Trans-Activator of Transcription Functionalized Nanoparticles. AB - We investigated the cellular uptake efficiencies of differently-sized silica nanoparticles in the presence and the absence of trans-activator of transcription (TAT) peptide. Silica nanoparticles incorporating fluorescent dye molecules with diameters of 30 to 800 nm were synthesized, and the surfaces of the silica nanoparticles were functionalized with TAT peptides or 3 aminopropyltriethoxysilane (APTES). Confocal microscopy and flow cytometry were used to determine the cellular locations and the uptake efficiencies of positively-charged silica nanoparticles (APTES- and TAT-) of various sizes from 30 to 800 nm. The cellular uptake efficiencies of all the differently-sized particles were significantly increased in the presence of TAT peptides. On the basis of an efficient TAT-mediated delivery system, we were able to show that TAT peptides could be used as effective cellular-uptake reagents, particularly for large particles. PMID- 27280252 TI - Nanolithography of Amyloid Precursor Protein Cleavage with beta-Secretase by Atomic Force Microscopy. AB - Cleavage of the amyloid precursor protein (APP) by secretases is critical in neural cell processes including the pathway for neural cell proliferation and that underlying the pathogenesis of Alzheimer's disease (AD). Understanding the mechanism of APP cleavage and development of a convenient tool for the accurate evaluation of APP cleavage intensity by secretases are very important in the development of new AD therapeutic targets. In this study, we developed a sophisticated technology to evaluate the APP cleavage mechanism at the nano molecular level by atomic force microscopic (AFM) nanolithography. APP was modified on a glass substrate; nanolithography of APP cleavage by beta-secretase modified AFM probe scanning was achieved. APP cleavage was verified by the AFM imaging and the fluorescent immunostaining. The present method will be very useful in understanding the molecular level of the APP cleavage mechanism by beta secretase in vitro; this method will facilitate inhibitor screening for the therapeutic target of AD. PMID- 27280254 TI - Guidance of Magnetic Nanocontainers for Treating Alzheimer's Disease Using an Electromagnetic, Targeted Drug-Delivery Actuator. AB - The "impermeability" of the blood-brain barrier (BBB) has hindered effective treatment of central nervous system (CNS) disorders such as Alzheimer's disease (AD), which is one of the most common neurodegenerative disorders. A drug can be delivered to a targeted disease site effectively by applying a strong electromagnetic force to the conjugate of a drug and magnetic nanocontainers. This study developed a novel nanotechnology-based strategy to deliver therapeutic agents to the brain via the BBB as a possible therapeutic approach for AD. First, a novel approach for an electromagnetic actuator for guiding nanocontainers is introduced. Then, we analyzed the in vivo uptake in mice experimentally to evaluate the capacity of the nanocontainers. In the mouse model, we demonstrated that magnetic particles can cross the normal BBB when subjected to external electromagnetic fields of 28 mT (0.43 T/m) and 79.8 mT (1.39 T/m). Our study also assessed the differential effects of pulsed (0.25, 0.5, and 1 Hz) and constant magnetic fields on the transport of particles across the BBB in mice injected with magnetic nanoparticles (MNPs) via a tail vein. The applied magnetic field was either kept constant or pulsed on and off. Relative to a constant magnetic field, the rate of MNP uptake and transport across the BBB was enhanced significantly by a pulsed magnetic field. Localization inside the brain was established using fluorescent MNPs. These results using 770-nm fluorescent carboxyl magnetic nanocontainers demonstrated the feasibility of the proposed electromagnetic targeted drug delivery actuator. These results establish an effective strategy for regulating the biodistribution of MNPs in the brain through the application of an external electromagnetic field. This might be a valuable targeting system for AD diagnosis and therapy. PMID- 27280253 TI - Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer. AB - MicroRNAs (miRNAs) are endogenous regulators of gene expression that play a pivotal role in biological processes spanning from global homeostasis to disease onset and progression. The ability to manipulate and induce cellular reequilibrium of deregulated miRNA expression profiles by inhibition of oncogenic miRNA or overexpression of tumor suppressor miRNA is a promising cancer strategy, but is currently hindered in application by the lack of nonviral delivery systems. Here we present a lipid nanoparticle (LNP) platform surface coated with Hyaluronic Acid (HA) for the delivery of mature tumor suppressor MicroRNA125a-5p to treat HER2 positive metastatic breast cancer. The delivery platform actively targets patient-derived metastatic breast cancer cells (21MT-1) isolated from the metastatic pleural effusion over normal breast tissue via an intrinsic HA-CD44 mediated endocytosis event, and has the ability to escape from the intracellular endolysosomal pathway for potent gene silencing. Knockdown of the HER2 proto oncogene at the level of transcription and translation was achieved following HA LNP mediated transfection with MicroRNA125a-5p. In addition, the PI3K/AKT and MAPK hyperactivated signaling pathways, cellular proliferation, and migration potential were also potently suppressed. Furthermore, the therapeutic efficacy of MicroRNA125a-5p by the HA-LNP platform was demonstrated to be significantly improved as compared to a commercial transfection reagent. This study highlights the therapeutic potential of MicroRNA125a-5p as a standalone treatment of HER2+ metastatic breast cancer via a translational nonviral delivery platform. These findings have major implications on future gene therapy regimens for breast cancer. PMID- 27280255 TI - Cell Adhesion and Growth on the Anodized Aluminum Oxide Membrane. AB - Nanotopological cues are popular tools for in vivo investigation of the extracellular matrix (ECM) and cellular microenvironments. The ECM is composed of multiple components and generates a complex microenvironment. The development of accurate in vivo methods for the investigation of ECM are important for disease diagnosis and therapy, as well as for studies on cell behavior. Here, we fabricated anodized aluminum oxide (AAO) membranes using sulfuric and oxalic acid under controlled voltage and temperature. The membranes were designed to possess three different pore and interpore sizes, AAO-1, AAO-2, and AAO-3 membranes, respectively. These membranes were used as tools to investigate nanotopology signal induced cell behavior. Cancerous cells, specifically, the OVCAR-8 cell line, were cultured on porous AAO membranes and the effects of these membranes on cell shape, proliferation, and viability were studied. AAO-1 membranes bearing small sized pores were found to maintain the spreading shape of the cultured cells. Cells cultured on AAO-2 and AAO-3 membranes, bearing large pore-sized AAO membranes, changed shape from spreading to rounding. Furthermore, cellular area decreased when cells were cultured on all three AAO membranes that confirmed decreased levels of focal adhesion kinase (FAK). Additionally, OVCAR-8 cells exhibited increased proliferation on AAO membranes possessing various pore sizes, indicating the importance of the nanosurface structure in regulating cell behaviors, such as cell proliferation. Our results suggest that porous-AAO membranes induced nanosurface regulated cell behavior as focal adhesion altered the intracellular organization of the cytoskeleton. Our results may find potential applications as tools in in vivo cancer research studies. PMID- 27280257 TI - [Not Available]. PMID- 27280256 TI - [Not Available]. PMID- 27280258 TI - [Not Available]. PMID- 27280259 TI - Commentary on Tarkiainen et al. (2016): Adding another piece to the puzzle of what explains socio-economic differences in alcohol-related mortality. PMID- 27280260 TI - Commentary on Lipperman-Kreda et al. (2016): Robust methods with a weak outcome measure still lead to consistent conclusions--even so, it may be time for recommendations to move from traditional tobacco control strategies to a relevant endgame strategy. PMID- 27280261 TI - From the PUBLISHER and EDITOR. PMID- 27280263 TI - From the SOMA PRESIDENT. PMID- 27280262 TI - James Thomas (Tom) Scott 1926-2015. PMID- 27280264 TI - From the NATO SOF Surgeon. PMID- 27280265 TI - Special Talk: An Interview With Dr. Richard Carmona. PMID- 27280266 TI - Spring Committee for Tactical Emergency Casualty Care (C-TECC)Update. PMID- 27280267 TI - Feature: Chimpanzees, our cultured cousins. PMID- 27280268 TI - Q & A: Liam Dolan. PMID- 27280269 TI - Retraction notice to "Predictive and prognostic value of ER-alpha36 expression in breast cancer patients treated with chemotherapy" [Steroids 84 (2014) 11-16]. PMID- 27280270 TI - Derivation of hybrid ES cell lines from two different strains of mice. AB - Parental origin-dependent expression of the imprinted genes is essential for mammalian development. Zfp57 maintains genomic imprinting in mouse embryos and ES cells. To examine the allelic expression patterns of the imprinted genes in ES cells, we obtained multiple hybrid ES clones that were directly derived from the blastocysts generated from the cross between mice on two different genetic backgrounds. The blastocyst-derived ES clones displayed largely intact DNA methylation imprint at the tested imprinted regions. These hybrid ES clones will be useful for future studies to examine the allelic expression of the imprinted genes in ES cells and their differentiated progeny. PMID- 27280271 TI - [The immortal cell]. PMID- 27280272 TI - [The prematures]. PMID- 27280273 TI - Eliminating Vaccine- Preventable Diseases Around The World. PMID- 27280274 TI - Tribute to Patrick J. Mulrow, MD. PMID- 27280281 TI - Protein Carbonyl as a Biomarker of Oxidative Stress in Severe Leptospirosis, and Its Usefulness in Differentiating Leptospirosis from Dengue Infections. AB - Pathogenesis of disease severity in leptospirosis is not clearly understood whether it is due to direct damage by pathogen or by adverse immune responses. Knowledge on biomarkers of oxidative stress which could be used in identifying patients with severe illness has shown to be of great value in disease management. Thus, the main aim of this study was to assess the damage to serum proteins and lipids, and their significance as biomarkers of oxidative stress in severe leptospirosis. In regions endemic for both leptospirosis and dengue, leptospirosis cases are often misdiagnosed as dengue during dengue epidemics. Therefore, the second aim was to assess the potential of the oxidative stress markers in differentiating severe leptospirosis from critical phase dengue. We measured serum antioxidants (uric acid and bilirubin), total antioxidant capacity (AOC), protein carbonyl (PC) and lipid hydroperoxide (LP) in patients with severe leptospirosis (n = 60), mild leptospirosis (n = 50), dengue during the critical phase (n = 30) and in healthy subjects (n = 30). All patient groups had similar total antioxidant capacity levels. However, the presence of significantly high uric acid and total bilirubin levels may reflect the degree of renal and hepatic involvement seen in severe leptospirosis patients (p<0.02). Serum PC and LP levels were significantly higher in leptospirosis patients compared to critical phase dengue infections (p<0.005). Moreover, high serum PC levels appear to differentiate SL from DC [area under the curve (AUC) = 0.96; p<0.001]. Serum PC may be a reliable biomarker of oxidative damage to serum proteins to identify severe leptospirosis patients (AUC = 0.99) and also to differentiate severe leptospirosis from mild cases (AUC = 0.78; p<0.005) indicating its contribution to pathogenesis. Use of serum PC as an indicator of leptospirosis severity and as an oxidative stress biomarker in differentiating leptospirosis from dengue would provide the opportunity to save lives via prompt patient management. PMID- 27280282 TI - Non-Uptake of HIV Testing in Children at Risk in Two Urban and Rural Settings in Zambia: A Mixed-Methods Study. AB - This article investigates reasons why children who were considered at risk of HIV were not taken for HIV testing by their caregivers. Qualitative and quantitative data collected in Zambia from 2010-11 revealed that twelve percent of caregivers who stated that they had been suspecting an HIV infection in a child in their custody had not had the child tested. Fears of negative reactions from the family were the most often stated reason for not testing a child. Experience of pre existing conflicts between the couple or within the family (aOR 1.35, 95% CI 1.00 1.82) and observed stigmatisation of seropositive children in one's own neighbourhood (aOR 1.69, 95% CI1.20-2.39) showed significant associations for not testing a child perceived at risk of HIV. Although services for HIV testing and treatment of children have been made available through national policies and programmes, some women and children were denied access leading to delayed diagnosis and treatment-not on the side of the health system, but on the household level. Social norms, such as assigning the male household head the power to decide over the use of healthcare services by his wife and children, jeopardize women's bargaining power to claim their rights to healthcare, especially in a conflict-affected relationship. Social norms and customary and statutory regulations that disadvantage women and their children must be addressed at every level-including the community and household-in order to effectively decrease barriers to HIV related care. PMID- 27280283 TI - Preclinical Studies of Mesenchymal Stem Cell (MSC) Administration in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis. AB - BACKGROUND: In the last two decades, mesenchymal stem cells (MSCs) have been pre clinically utilized in the treatment of a variety of kinds of diseases including chronic obstructive pulmonary disease (COPD). The aim of the current study was to systematically review and conduct a meta-analysis on the published pre-clinical studies of MSC administration in the treatment of COPD in animal models. METHODS AND RESULTS: A systematic search of electronic databases was performed. Statistical analysis was performed using the Comprehensive Meta-Analysis software (Version 3). The pooled Hedges's g with 95% confidence intervals (95% CIs) was adopted to assess the effect size. Random effect model was used due to the heterogeneity between the studies. A total of 20 eligible studies were included in the current systematic review. The overall meta-analysis showed that MSC administration was significantly in favor of attenuating acute lung injury (Hedges's g = -2.325 +/- 0.145 with 95% CI: -2.609 ~ -2.040, P < 0.001 for mean linear intercept, MLI; Hedges's g = -3.488 +/- 0.504 with 95% CI: -4.476 ~ 2.501, P < 0.001 for TUNEL staining), stimulating lung tissue repair (Hedges's g = 3.249 +/- 0.586 with 95% CI: 2.103~ 4.394, P < 0.001) and improving lung function (Hedges's g = 2.053 +/- 0.408 with 95% CI: 1.253 ~ 2.854, P< 0.001). The mechanism of MSC therapy in COPD is through ameliorating airway inflammation (Hedges's g = -2.956 +/- 0.371 with 95% CI: -3.683 ~ -2.229, P< 0.001) and stimulating cytokine synthesis that involves lung tissue repair (Hedges's g = 3.103 +/- 0.734 with 95% CI: 1.664 ~ 4.541, P< 0.001). CONCLUSION: This systematic review and meta-analysis suggest a promising role for MSCs in COPD treatment. Although the COPD models may not truly mimic COPD patients, these pre clinical studies demonstrate that MSC hold promise in the treatment of chronic lung diseases including COPD. The mechanisms of MSCs role in preclinical COPD treatment may be associated with attenuating airway inflammation as well as stimulating lung tissue repair. PMID- 27280285 TI - Correction: Antiphospholipid Antibody and Risk of Retinal Vein Occlusion: A Systematic Review and Meta-Analysis. AB - [This corrects the article DOI: 10.1371/journal.pone.0122814.]. PMID- 27280284 TI - The Race against Protease Activation Defines the Role of ESCRTs in HIV Budding. AB - HIV virions assemble on the plasma membrane and bud out of infected cells using interactions with endosomal sorting complexes required for transport (ESCRTs). HIV protease activation is essential for maturation and infectivity of progeny virions, however, the precise timing of protease activation and its relationship to budding has not been well defined. We show that compromised interactions with ESCRTs result in delayed budding of virions from host cells. Specifically, we show that Gag mutants with compromised interactions with ALIX and Tsg101, two early ESCRT factors, have an average budding delay of ~75 minutes and ~10 hours, respectively. Virions with inactive proteases incorporated the full Gag-Pol and had ~60 minutes delay in budding. We demonstrate that during budding delay, activated proteases release critical HIV enzymes back to host cytosol leading to production of non-infectious progeny virions. To explain the molecular mechanism of the observed budding delay, we modulated the Pol size artificially and show that virion release delays are size-dependent and also show size-dependency in requirements for Tsg101 and ALIX. We highlight the sensitivity of HIV to budding "on-time" and suggest that budding delay is a potent mechanism for inhibition of infectious retroviral release. PMID- 27280287 TI - 2000 Years of Grazing History and the Making of the Cretan Mountain Landscape, Greece. AB - Understanding the processes that led to the recent evolution of Mediterranean landscapes is a challenging question that can be addressed with paleoecological data. Located in the White Mountains of Crete, Asi Gonia peat bog constitutes an exceptional 2000-years-long sedimentary archive of environmental change. In this study, we document the making of the White Mountains landscape and assess human impact on ecosystem trajectories. The paleoenvironmental reconstruction is based on high-resolution analyses of sediment, pollen, dung fungal spores and charcoal obtained from a 6-m core collected from the bog. Multiproxy analyses and a robust chronological control have shed light on anthropogenic and natural processes that have driven ecological changes, giving rise to the present-day Mediterranean ecosystem. Our results suggest that sediment accumulation began during the transition from the Hellenistic to the Roman period, likely due to watershed management. The evolution of the peat bog as well as vegetation dynamics in the surrounding area were linked to past climate changes but were driven by human activities, among which breeding was of great importance. Charcoal analysis reveals that fire was largely used for the construction and maintenance of sylvo agropastoral areas. Pollen data allow the identification of three main vegetation assemblages: 1) evergreen oak forest (before ca. 850 AD), 2) heather maquis (ca. 850 to 1870 AD), 3) phrygana/steppe landscape. Rapid changes between phases in vegetation development are associated with tipping-points in ecosystem dynamics resulting from anthropogenic impact. The modern ecosystem did not get established until the 20th century, and it is characterized by biodiversity loss along with a dramatic drying of the peat bog. PMID- 27280286 TI - Dihydrostreptomycin Directly Binds to, Modulates, and Passes through the MscL Channel Pore. AB - The primary mechanism of action of the antibiotic dihydrostreptomycin is binding to and modifying the function of the bacterial ribosome, thus leading to decreased and aberrant translation of proteins; however, the routes by which it enters the bacterial cell are largely unknown. The mechanosensitive channel of large conductance, MscL, is found in the vast majority of bacterial species, where it serves as an emergency release valve rescuing the cell from sudden decreases in external osmolarity. While it is known that MscL expression increases the potency of dihydrostreptomycin, it has remained unclear if this effect is due to a direct interaction. Here, we use a combination of genetic screening, MD simulations, and biochemical and mutational approaches to determine if dihydrostreptomycin directly interacts with MscL. Our data strongly suggest that dihydrostreptomycin binds to a specific site on MscL and modifies its conformation, thus allowing the passage of K+ and glutamate out of, and dihydrostreptomycin into, the cell. PMID- 27280288 TI - Insights into Sexual Precocity of Female Oriental River Prawn Macrobrachium nipponense through Transcriptome Analysis. AB - BACKGROUND: The oriental river prawn (Macrobrachium nipponense) is the most prevalent aquaculture species in China. The sexual precocity in this species has received considerable attention in recent years because more and more individuals matured at a small size, which devalues the commercial production. In this study, we developed deep-coverage transcriptomic sequencing data for the ovaries of sexually precocious and normal sexually mature M. nipponense using next generation RNA sequencing technology and attempted to provide the first insight into the molecular regulatory mechanism of sexual precocity in this species. RESULTS: A total of 63,336 unigenes were produced from the ovarian cDNA libraries of sexually precocious and normal sexually mature M. nipponense using Illumina HiSeq 2500 platform. Through BLASTX searches against the NR, STRING, Pfam, Swissprot and KEGG databases, 15,134 unigenes were annotated, accounting for 23.89% of the total unigenes. 5,195 and 3,227 matched unigenes were categorized by GO and COG analysis respectively. 15,908 unigenes were consequently mapped into 332 KEGG pathways, and many reproduction-related pathways and genes were identified. Moreover, 26,008 SSRs were identified from 18,133 unigenes. 80,529 and 80,516 SNPs were yielded from ovarian libraries of sexually precocious and normal sexually mature prawn, respectively, and 29,851 potential SNPs between these two groups were also predicted. After comparing the ovarian libraries of sexually precocious and normal sexually mature prawn, 549 differentially expressed genes (DEGs) and 9 key DEGs that may be related to sexual precocity of M. nipponense were identified. 20 DEGs were selected for validation by quantitative real-time PCR (QPCR) and 19 DEGs show consistent expression between QPCR and RNAseq-based differential expression analysis datasets. CONCLUSION: This is the first report on the large-scale RNA sequencing of ovaries of sexually precocious and normal sexually mature M. nipponense. The annotated transcriptome data will provide fundamental support for future research into the reproduction biology of M. nipponense. The large number of candidate SNPs and SSRs detected in this study could be used as genetic markers for population genetics and functional genomics in this species. More importantly, many DEGs, especially nine key DEGs between sexually precocious and normal sexually mature prawns were identified, which will dramatically improve understanding of molecular regulatory mechanism of sexual precocity of this species. PMID- 27280289 TI - MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway. AB - Endothelium-dependent angiogenesis is thought to be a crucial step in cancer progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) contributed to the vasculogenic mimicry in gastric cancer (GC), but it remains unknown whether MACC1 promotes endothelium-dependent angiogenesis of GC and whether TWIST1 is involved in this process. In the present study, we detected MACC1 expression and microvessel density (MVD) by immunohistochemistry in 159 patients with stage I-III GC, and investigated the role of TWIST1 and vascular endothelial growth factor A (VEGF-A) in MACC1-induced endothelium-dependent angiogenesis using nude mice with GC xenografts, and human umbilical vein endothelial cells (HUVECs) that were co-cultured with conditioned media from overexpression and interference MACC1 GC cells. We found that MACC1 expression was positively correlated with an increased MVD and tumor recurrence in GC patients. In GC xenograft models, MACC1 elevated MVD and upregulated the expression of VEGF-A as well as accelerated tumor growth. In addition, MACC1 obviously increased the expression of TWIST1 and induced tube-like formation of HUVECs, whereas attenuation of TWIST1 suppressed the protein expression of VEGF-A and repealed the effect of MACC1 on tube formation. Our findings shed light on the function of MACC1 in endothelium-dependent angiogenesis of GC and suggest potential prognostic and therapeutic value. PMID- 27280290 TI - Genetic Links between Recombination and Speciation. PMID- 27280291 TI - Pharmacokinetic-Pharmacodynamic Analysis on Inflammation Rat Model after Oral Administration of Huang Lian Jie Du Decoction. AB - Huang-Lian-Jie-Du Decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK) and pharmacodynamic (PD) data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR) of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM) method. Additionally, the levels of 7 cytokines (CKs) in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax) and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta, IL-10, and macrophage inflammatory protein-2 (MIP-2) and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that HLJDD may restrain inflammation synergistically via its major constituents (alkaloids, flavonoids and iridoids). A correlation between the exposure concentration of different types of compounds and their anti inflammatory effects in the body was shown. This study provides a comprehensive understanding of the anti-inflammatory activity of HLJDD. PMID- 27280292 TI - Sleep Quality and Factors Influencing Self-Reported Sleep Duration and Quality in the General Internal Medicine Inpatient Population. AB - BACKGROUND: Sleep quality in hospitalized Canadian General Internal Medicine patients is not well characterized. Our goals were to characterize hospital sleep quality in this population and identify potentially modifiable barriers to good sleep. METHODS: GIM inpatients at a quaternary centre in Edmonton, Canada completed a survey, including the Verran-Snyder Halpern (VSH) questionnaire, to characterize the previous night's sleep within 48 hours prior to discharge. A chart review was also completed to assess comorbidities, discharge diagnoses, and pharmaceutical sleep aid use. RESULTS: Patients reported significantly worse nighttime sleep duration in hospital compared with home (mean 5.5 versus 7.0 hours per night, p < 0.0001). Sleep quality was poor, as measured by the VSH disturbance (mean 371), effectiveness (190), and supplementation (115) subscales. Variables independently associated with poorer sleep duration in multivariable regression include prior diagnosis of sleep disorder and multi-patient occupancy rooms. Age, sex, admitting diagnosis, length of stay, frequency of vital checks, and use of sleep pharmaceuticals during the index hospitalization were not associated with sleep duration. The most frequently reported reasons for poor sleep included noise (59%), nursing interruptions (30%), uncomfortable beds (18%), bright lights (16%), unfamiliar surroundings (14%), and pain (9%). CONCLUSIONS: Sleep quality for GIM inpatients is significantly worse in hospital than at home. There is a need to test non-pharmacologic interventions to address the most frequently identified factors causing poor sleep hygiene for GIM inpatients. PMID- 27280293 TI - Spatio-Temporal History of HIV-1 CRF35_AD in Afghanistan and Iran. AB - HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD) has an important position in the epidemiological profile of Afghanistan and Iran. Despite the presence of this clade in Afghanistan and Iran for over a decade, our understanding of its origin and dissemination patterns is limited. In this study, we performed a Bayesian phylogeographic analysis to reconstruct the spatio-temporal dispersion pattern of this clade using eligible CRF35_AD gag and pol sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_AD-like pol sequence available from USA). Bayesian Markov Chain Monte Carlo algorithm was implemented in BEAST v1.8.1. Between-country dispersion rates were tested with Bayesian stochastic search variable selection method and were considered significant where Bayes factor values were greater than three. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.7). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersion of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting it not to be a true CRF35_AD lineage. Potential factors contributing to viral exchange between Afghanistan and Iran could be injection drug networks and mass migration of Afghan refugees and labours to Iran, which calls for extensive preventive efforts. PMID- 27280295 TI - The Development of Quality Control Genotyping Approaches: A Case Study Using Elite Maize Lines. AB - Quality control (QC) of germplasm identity and purity is a critical component of breeding and conservation activities. SNP genotyping technologies and increased availability of markers provide the opportunity to employ genotyping as a low cost and robust component of this QC. In the public sector available low-cost SNP QC genotyping methods have been developed from a very limited panel of markers of 1,000 to 1,500 markers without broad selection of the most informative SNPs. Selection of optimal SNPs and definition of appropriate germplasm sampling in addition to platform section impact on logistical and resource-use considerations for breeding and conservation applications when mainstreaming QC. In order to address these issues, we evaluated the selection and use of SNPs for QC applications from large DArTSeq data sets generated from CIMMYT maize inbred lines (CMLs). Two QC genotyping strategies were developed, the first is a "rapid QC", employing a small number of SNPs to identify potential mislabeling of seed packages or plots, the second is a "broad QC", employing a larger number of SNP, used to identify each germplasm entry and to measure heterogeneity. The optimal marker selection strategies combined the selection of markers with high minor allele frequency, sampling of clustered SNP in proportion to marker cluster distance and selecting markers that maintain a uniform genomic distribution. The rapid and broad QC SNP panels selected using this approach were further validated using blind test assessments of related re-generation samples. The influence of sampling within each line was evaluated. Sampling 192 individuals would result in close to 100% possibility of detecting a 5% contamination in the entry, and approximately a 98% probability to detect a 2% contamination of the line. These results provide a framework for the establishment of QC genotyping. A comparison of financial and time costs for use of these approaches across different platforms is discussed providing a framework for institutions involved in maize conservation and breeding to assess the resource use effectiveness of QC genotyping. Application of these research findings, in combination with existing QC approaches, will ensure the regeneration, distribution and use in breeding of true to type inbred germplasm. These findings also provide an effective approach to optimize SNP selection for QC genotyping in other species. PMID- 27280296 TI - Capacitacion-accion participativa: una experiencia de 24 anos en las comunidades rurales de Oaxaca, Mexico. AB - Resumen: En este articulo presentamos el proyecto de capacitacion llevado a cabo en comunidades de la sierra y costa de Oaxaca, Mexico, desde 1991, por el Centro de Capacitacion Integral para Promotores Comunitarios (CECIPROC). La decision de hacer este trabajo en Oaxaca responde a que ese estado ocupa uno de los primeros lugares de marginacion y de desnutricion en menores de 5 anos. El objetivo es describir un modelo de capacitacion y compartir parte de las experiencias derivadas, tanto del modelo como del trabajo realizado en las distintas areas (nutricion y alimentacion, salud comunitaria, ecologia y etnobotanica, y educacion y organizacion), por promotores mujeres y hombres en sus comunidades. La experiencia obtenida en 24 anos muestra la factibilidad tecnica y social del proyecto en el ambito de la salud, el reconocimiento social del proyecto del CECIPROC como un organismo civil que ha aportado alternativas como solucion a la problematica de salud, el hacer suyo el proyecto por algunos promotores y los diferentes obstaculos a los que se ha enfrentado. Enfatizamos el hecho de que la situacion socioeconomica y politica prevaleciente en el estado de Oaxaca es una limitante para el buen desarrollo de los programas colectivos de salud, e insistimos en la necesidad de compartir nuestras experiencias para que puedan ser utilizadas en la planificacion y ejecucion de otros proyectos. PMID- 27280294 TI - Distinct Roles for Intracellular and Extracellular Lipids in Hepatitis C Virus Infection. AB - Hepatitis C is a chronic liver disease that contributes to progressive metabolic dysfunction. Infection of hepatocytes by hepatitis C virus (HCV) results in reprogramming of hepatic and serum lipids. However, the specific contribution of these distinct pools of lipids to HCV infection remains ill defined. In this study, we investigated the role of hepatic lipogenesis in HCV infection by targeting the rate-limiting step in this pathway, which is catalyzed by the acetyl-CoA carboxylase (ACC) enzymes. Using two structurally unrelated ACC inhibitors, we determined that blockade of lipogenesis resulted in reduced viral replication, assembly, and release. Supplementing exogenous lipids to cells treated with ACC inhibitors rescued HCV assembly with no effect on viral replication and release. Intriguingly, loss of viral RNA was not recapitulated at the protein level and addition of 2-bromopalmitate, a competitive inhibitor of protein palmitoylation, mirrored the effects of ACC inhibitors on reduced viral RNA without a concurrent loss in protein expression. These correlative results suggest that newly synthesized lipids may have a role in protein palmitoylation during HCV infection. PMID- 27280298 TI - Is honey an effective treatment for acute cough in children? AB - Cough represents one of the most common reasons for pediatrician consultations. There are many available treatments for symptomatic relief, including honey. Despite its wide availability, there is little knowledge about its benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including three randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded the use of honey probably decreases the severity and frequency of cough, improves the quality of parent's and patient's sleep, and does not have side effects. PMID- 27280297 TI - Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection. AB - Maternally-derived antibodies (MDAs) can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP) or intranasal (IN) route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN) was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition. PMID- 27280300 TI - Effects of Adjacent Vehicles on Judgments of a Lead Car During Car Following. AB - OBJECTIVE: Two experiments were conducted to determine whether detection of the onset of a lead car's deceleration and judgments of its time to contact (TTC) were affected by the presence of vehicles in lanes adjacent to the lead car. BACKGROUND: In a previous study, TTC judgments of an approaching object by a stationary observer were influenced by an adjacent task-irrelevant approaching object. The implication is that vehicles in lanes adjacent to a lead car could influence a driver's ability to detect the lead car's deceleration and to make judgments of its TTC. METHOD: Displays simulated car-following scenes in which two vehicles in adjacent lanes were either present or absent. Participants were instructed to respond as soon as the lead car decelerated (Experiment 1) or when they thought their car would hit the decelerating lead car (Experiment 2). RESULTS: The presence of adjacent vehicles did not affect response time to detect deceleration of a lead car but did affect the signal detection theory measure of sensitivity d' and the number of missed deceleration events. Judgments of the lead car's TTC were shorter when adjacent vehicles were present and decelerated early than when adjacent vehicles were absent. CONCLUSION: The presence of vehicles in nearby lanes can affect a driver's ability to detect a lead car's deceleration and to make subsequent judgments of its TTC. APPLICATION: Results suggest that nearby traffic can affect a driver's ability to accurately judge a lead car's motion in situations that pose risk for rear-end collisions. PMID- 27280301 TI - Type 2 Diabetes and Heart Failure: Challenges and Solutions. AB - Increasing numbers of older patients with type 2 diabetes, and their improved survival from cardiovascular events is seeing a massive increase in patients with both diabetes and heart failure. Already, at least a third of all patients with heart failure have diabetes. This close association is partly because all the major risk factors for heart failure also cluster in patients with type 2 diabetes, including obesity, hypertension, advanced age, sleep apnoea, dyslipidaemia, anaemia, chronic kidney disease, and coronary heart disease. However, diabetes may also cause cardiac dysfunction in the absence of overt macrovascular disease, as well as complicate the response to therapy. Current management is focused on targeting modifiable risk factors for heart failure including hyperglycaemia, dyslipidaemia, hypertension, obesity and anemia. But although these are important risk markers, none of these interventions substantially prevents heart failure or improves its outcomes. Much more needs to be done to focus on this issue, including the inclusion of hospital admission for heart failure as a pre-specified component of the primary composite cardiovascular outcomes and new trials in heart failure management specifically in the context of diabetes. PMID- 27280302 TI - Chronic Heart Failure and Comorbid Renal Dysfunction - A Focus on Type 2 Cardiorenal Syndrome. AB - The most important advancements in the Cardiorenal syndrome (CRS) are its definition and subsequent classifications. When the predominant pathology and pathophysiology is the heart, i.e. chronic heart failure (CHF), and where any renal impairment (RI) subsequent to this is secondary, the classification is type 2 CRS. There are unique differences in the pathophysiology and progression of individual subclasses. It is important to understand the evolution of CHF and consequences of subsequent RI as they are becoming increasingly prevalent, aggravate morbidity and mortality and limit many therapeutic options. In this paper we discuss the significance of the type 2 CRS patients in the context of the thematic series. PMID- 27280303 TI - Phase 4 Studies in Heart Failure - What is Done and What is Needed? AB - Congestive heart failure (CHF) therapeutics is generated through a well-described evidence generating process. Phases 1 - 3 of this process are required prior to approval and widespread clinical use. Phase 3 in almost all cases is a methodologically sound randomized controlled trial (RCT). After this phase it is generally accepted that the treatment has a significant, independent and prognostically beneficial effect on the pathophysiological process. A major criticism of RCTs is the population to whom the result is applicable. When this population is significantly different from the trial cohort the external validity comes into question. Should the continuation of the evidence generating process continue these problems might be identified. Post marketing surveillance through phase 4 and comparative effectiveness studies through phase 5 trials are often underperformed in comparison to the RCT. These processes can help identify remote adverse events and define new hypotheses for community level benefits. This review is aimed at exploring the post-marketing scene for CHF therapeutics from an Australian health system perspective. We explore the phases of clinical trials, the level of evidence currently available and options for ensuring greater accountability for community level CHF clinical outcomes. PMID- 27280305 TI - Towards Optimal Heart Failure Care: Couples-Oriented Strategies to Improve Patient Adherence and Health Outcomes. AB - Psychosocial factors play an important role in the development and progression of cardiovascular diseases (CVD), such as chronic heart failure (CHF). In particular, psycho-cognitive disturbance is common in CHF, which presents additional challenges to secondary prevention and management strategies. This review provides a summary of the contemporary psycho-cardiology literature, including coverage of common mood and cognitive symptoms, and explores some of the pathophysiologic evidence linking psycho-cognition to CHF, with particular emphasis on sympathetic nervous system activation and neuroendocrine functioning. Social support is identified as a strategy by which to reduce depressive symptoms, manage cognitive impairment and to, potentially, improve health outcomes through improved patient self care and adherence. Recent research outcomes suggest that the integration of family caregivers into CHF psycho educational disease management programs, as providers and recipients of support, may achieve best outcomes. In this regard, couples-oriented strategies that promote communication, emotional attachment and support may enhance healthpromoting behaviours in patients and their partners. PMID- 27280304 TI - Cellular Therapy for Heart Failure. AB - The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. PMID- 27280308 TI - Induced radioactivity of a GSO scintillator by secondary fragments in carbon ion therapy and its effects on in-beam OpenPET imaging. AB - The accumulation of induced radioactivity within in-beam PET scanner scintillators is of concern for its long-term clinical usage in particle therapy. To estimate the effects on OpenPET which we are developing for in-beam PET based on GSOZ (Zi doped Gd2SiO5), we measured the induced radioactivity of GSO activated by secondary fragments in a water phantom irradiation by a (12)C beam with an energy of 290 MeV u(-1). Radioisotopes of Na, Ce, Eu, Gd, Nd, Pm and Tb including positron emitters were observed in the gamma ray spectra of the activated GSO with a high purity Ge detector and their absolute radioactivities were calculated. We used the Monte Carlo simulation platform, Geant4 in which the observed radioactivity was assigned to the scintillators of a precisely reproduced OpenPET and the single and coincidence rates immediately after one treatment and after one-year usage were estimated for the most severe conditions. Comparing the highest coincidence rate originating from the activated scintillators (background) and the expected coincidence rate from an imaging object (signal), we determined the expected signal-to-noise ratio to be more than 7 within 3 min and more than 10 within 1 min from the scan start time. We concluded the effects of scintillator activation and their accumulation on the OpenPET imaging were small and clinical long-term usage of the OpenPET was feasible. PMID- 27280306 TI - Contextualizing Genetics for Regional Heart Failure Care. AB - Congestive heart failure (CHF) is a chronic and often devastating cardiovascular disorder with no cure. There has been much advancement in the last two decades that has seen improvements in morbidity and mortality. Clinicians have also noted variations in the responses to therapies. More detailed observations also point to clusters of diseases, phenotypic groupings, unusual severity and the rates at which CHF occurs. Medical genetics is playing an increasingly important role in answering some of these observations. This developing field in many respects provides more information than is currently clinically applicable. This includes making sense of the established single gene mutations or uncommon private mutations. In this thematic series which discusses the many factors that could be relevant for CHF care, once established treatments are available in the communities; this section addresses a contextual role for medical genetics. PMID- 27280309 TI - Depression, help-seeking perceptions, and perceived family functioning among Spanish-Dominant Hispanics and Non-Hispanic Whites. AB - INTRODUCTION: Guided by Beck's (1967) cognitive theory of depression, we assessed whether perceived family functioning (PFF) mediated the relationship between depressive symptomatology and help-seeking inclinations. METHODS: Study 1 included 130 Spanish-Dominant Hispanics and Study 2 included 124 Non-Hispanic Whites obtained using online crowd sourcing. Participants completed measures of depressive symptomatology, PFF, and several scales measuring aspects of help seeking inclinations and self-stigma. Study 2 also included an experiment. With an eye toward potential future interventions, we assessed the malleability of PFF. Specifically, participants were randomly assigned to recall positive or negative family experiences and then PFF was measures for a second time. RESULTS: Both studies found PFF mediates the relationship between depressive symptomatology and the help seeking scales. Among non-depressed people, the positive manipulation improved PFF; however, among participants with elevated depressive symptomatology, writing about a positive family experience worsened PFF. LIMITATION: With the exception of the experiment, most of the data were cross-sectional. For the experiment, it is possible that different manipulations or primes could have different effects. CONCLUSION: Whether investigating responses from Spanish-Dominant Hispanics or Non-Hispanic Whites, PFF mediates the negative relationship between heightened depressive symptomatology and familial help-seeking beliefs, as well as self-stigma. However, even though the mediation analysis offers preliminary support that increasing PFF can potentially increase help-seeking behaviors of Hispanic and Non-Hispanic White people with depression, the results of the interaction analysis, specifically the negative impact of writing about positive family memories on people with elevated depression, illustrates the challenges of persuading people with depression. PMID- 27280310 TI - Cardiovascular Monitoring With Trastuzumab Therapy: How Frequent Is Too Frequent? PMID- 27280311 TI - Managing comorbid obesity and depression through clinical pharmacotherapies. AB - INTRODUCTION: Obesity and mood disorders co-occur more often than expected by chance alone. As no randomized, controlled pharmacotherapy trials have been conducted in obese patients with an active mood disorder, it is unclear how to use medication to treat this patient group. AREAS COVERED: We briefly overview the relationship between obesity and mood disorders; the effects of psychotropic medications commonly used in mood disorders on body weight; the psychiatric effects of available anti-obesity medications; and highlight the few treatment studies of medications in obese patients with mood disorders or depressive symptoms. As binge eating and psychotropic-induced weight gain are common correlates of obese patients with mood disorders, we also provide brief overviews of the pharmacotherapy of these conditions. EXPERT OPINION: When treating a patient with a mood disorder and obesity, both conditions need to be a focus of clinical attention. Psychotropic medications that have minimal weight gain effects should be used if possible. Weight-loss agents can probably be used in some mood disorder patients, but must be done so cautiously and with a full understanding of their potential psychiatric effects and interactions with psychotropic medications. Knowledge of the pharmacotherapy of binge eating and psychotropic-induced weight gain is also crucial. PMID- 27280307 TI - Heart Failure in Minority Populations - Impediments to Optimal Treatment in Australian Aborigines. AB - Chronic heart failure (CHF) among Aboriginal/Indigenous Australians is endemic. There are also grave concerns for outcomes once acquired. This point is compounded by a lack of prospective and objective studies to plan care. To capture the essence of the presented topic it is essential to broadly understand Indigenous health. Key words such as 'worsening', 'gaps', 'need to do more', 'poorly studied', or 'future studies should inform' occur frequently in contrast to CHF research for almost all other groups. This narrative styled opinion piece attempts to discuss future directions for CHF care for Indigenous Australians. We provide a synopsis of the problem, highlight the treatment gaps, and define the impediments that present hurdles in optimising CHF care for Indigenous Australians. PMID- 27280312 TI - Extent of altered white matter in unilateral and bilateral periventricular white matter lesions in children with unilateral cerebral palsy. AB - AIMS: To investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function. METHODS AND PROCEDURES: Diffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test). OUTCOMES AND RESULTS: Children with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups. CONCLUSIONS AND IMPLICATIONS: Periventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction. PMID- 27280313 TI - Spectroscopic Line Shapes of Vibrational Quanta in the Presence of Molecular Resonances. AB - Line shapes of molecular vibrational quanta in inelastic electron tunneling spectroscopy may indicate the strength of electron-vibration coupling, the hybridization of the molecule with its environment, and the degree of vibrational damping by electron-hole pair excitation. Bare as well as C60-terminated Pb tips of a scanning tunneling microscope and clean as well as C60-covered Pb(111) surfaces were used in low-temperature experiments. Depending on the overlap of orbital and vibrational spectral ranges different spectroscopic line shapes of molecular vibrational quanta were observed. The energy range covered by the molecular resonance was altered by modifying the adsorption configuration of the molecule terminating the tip apex. Concomitantly, the line shapes of different vibrational modes were affected. The reported observations represent an experimental proof to theoretical predictions on the contribution from resonant processes to inelastic electron tunneling. PMID- 27280314 TI - Pharmaceutical studies during the Second Empire in the Gaceta Medica de Mexico. AB - Pharmaceutical activities during the Second Empire have been neglected by historians of science in recent decades, even though pharmacy was an important discipline in Mexico City. This is shown by analyzing 12 papers published in the Gaceta Medica de Mexico, the journal of the Sociedad Medica de Mexico. Examination of these papers helps us understand the interests, practices and pharmaceutical activities of some of this group's physicians and pharmacists, as well as detailing scientific endorsement of the therapeutic use of Mexican flora. This allows us to trace a historical continuity in the activities of pharmacists in the capital city throughout the nineteenth century. Abstract Pharmaceutical activities during the Second Empire have been neglected by historians of science in recent decades, even though pharmacy was an important discipline in Mexico City. This is shown by analyzing 12 papers published in the Gaceta Medica de Mexico, the journal of the Sociedad Medica de Mexico. Examination of these papers helps us understand the interests, practices and pharmaceutical activities of some of this group's physicians and pharmacists, as well as detailing scientific endorsement of the therapeutic use of Mexican flora. This allows us to trace a historical continuity in the activities of pharmacists in the capital city throughout the nineteenth century. PMID- 27280315 TI - International cooperation in health: the case of Fiocruz. PMID- 27280316 TI - The inclusion of international migrants in Brazilian healthcare system policies: the case of Haitians in the state of Amazonas. PMID- 27280317 TI - Training in epidemiology and health surveillance: Tripartite Cooperation between Brazil, Cuba, and Haiti. PMID- 27280318 TI - Difunctionalization of Styrenes with Perfluoroalkyl and tert-Butylperoxy Radicals: Room Temperature Synthesis of (1-(tert-Butylperoxy)-2-perfluoroalkyl) ethylbenzene. AB - A novel strategy for the difunctionalization of styrenes was developed. This synthesis includes the use of electrophilic perfluoroalkyl and tert-butylperoxy radicals and produces (1-(tert-butylperoxy)-2-perfluoroalkyl)ethylbenzene at room temperature, which has been traditionally difficult to synthesize. With at least four radical species included in the transformation, its high chemoselectivity was extraordinary; the results were further elucidated using computational studies. The methodology also holds a good potential for application as a result of its mild reaction conditions, ease of further modification, and insensitivity to moisture and air. PMID- 27280319 TI - Velocity of Visual Field Progression Implicated in Falls. PMID- 27280322 TI - Erratum: Vol. 65, No. 20. AB - In the MMWR report, "Possible Zika Virus Infection Among Pregnant Women - United States and Territories, May 2016," the following persons should be included in the Zika and Pregnancy Working Group: "Nina Ahmad, New York State Department of Health; Jennifer White, New York State Department of Health." PMID- 27280320 TI - Spirituality, emotional distress, and post-traumatic growth in breast cancer survivors and their partners: an actor-partner interdependence modeling approach. AB - BACKGROUND: The association between spirituality and emotional health has been well documented in healthy individuals. A small literature has shown that spirituality plays a role in well-being for some breast cancer (BC) survivors; however, this link is virtually unexplored in partners/spouses of survivors. The current study aimed to assess the relationship between spirituality, emotional distress, and post-traumatic growth for BC survivors and their partners using a dyadic analyses approach. METHODS: A total of 498 couples who were 3-8 years post BC diagnosis were recruited from the Eastern Oncology Group database. RESULTS: For BC survivors and their partners, greater levels of spirituality were associated with increases in their own post-traumatic growth. There was no relation between BC and partner spirituality and their own emotional distress, but partner's spirituality was associated with reduced occurrence of intrusive thoughts in the BC survivor. In contrast, BC survivors' spirituality was found to be wholly unrelated to partner's mental health and adjustment. CONCLUSIONS: Following diagnosis and treatment, spirituality appears to associate with positive growth in BC survivors and their partners. However, BC survivor and partner spirituality seem to be ineffective at impacting the other's post traumatic growth or emotional distress, with the exception of intrusive thoughts. Dyadic analysis takes into account the reciprocal influence of close relationships on health and is an important and under-utilized methodology in behavioral oncology research and clinical practice. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27280321 TI - Phosphorylation of the mitochondrial ATP-sensitive potassium channel occurs independently of PKCepsilon in turtle brain. AB - Neurons from the western painted turtle (Chrysemys picta bellii) are remarkably resilient to anoxia. This is partly due to a reduction in the permeability of excitatory glutamatergic ion channels, initiated by mitochondrial ATP-sensitive K(+) (mK(+)ATP) channel activation. The aim of this study was to determine if: 1) PKCepsilon, a kinase associated with hypoxic stress tolerance, is more highly expressed in turtle brain than the anoxia-intolerant rat brain; 2) PKCepsilon translocates to the mitochondrial membrane during anoxia; 3) PKCepsilon modulates mK(+)ATP channels at the Thr-224 phosphorylation site on the Kir6.2 subunit; and 4) Thr-224 phosphorylation sensitises mK(+)ATP channels to anoxia. Soluble and mitochondrial-rich particulate fractions of turtle and rat cerebral cortex were isolated and PKCepsilon expression was determined by Western blot, which revealed that turtle cortical PKCepsilon expression was half that of the rat. Following the transition to anoxia, no changes in PKCepsilon expression in either the soluble or particulate fraction of the turtle cortex were observed. Furthermore, incubation of tissue with tat-conjugated activator or inhibitor peptides had no effect on the amount of PKCepsilon in either fraction. However, we observed a 2 fold increase in Thr-224 phosphorylation following 1h of anoxia. The increased Thr-224 phosphorylation was blocked by the general kinase inhibitor staurosporine but this did not affect the latency or magnitude of mK(+)ATP channel-mediated mitochondrial depolarization following anoxia, as indicated by rhodamine-123. We conclude that PKCepsilon does not play a role in the onset of mitochondrial depolarization and therefore glutamatergic channel arrest in turtle cerebral cortex. PMID- 27280323 TI - Structural and material properties of human foot tendons. AB - BACKGROUNDS: The aim of this study was to assess the mechanical properties of the main balance tendons of the human foot in vitro reporting mechanical structural properties and mechanical material properties separately. Tendon structural properties are relevant for clinical applications, for example in orthopedic surgery to elect suitable replacements. Tendon material properties are important for engineering applications such as the development of refined constitutive models for computational simulation or in the design of synthetic materials. METHODS: One hundred uniaxial tensile tests were performed to obtain the mechanical response of the main intrinsic and extrinsic human foot tendons. The specimens were harvested from five frozen cadaver feet including: Extensor and Flexor tendons of all toes, Tibialis Anterior and Posterior tendons and Peroneus Brevis and Longus tendons. FINDINGS: Cross-sectional area, load and strain failure, Young's modulus and ultimate tensile stress are reported as a reference of foot tendon mechanical properties. Two different behaviors could be differentiated. Tibialis and Peroneus tendons exhibited higher values of strain failure compared to Flexor and Extensor tendons which had higher Young's modulus and ultimate tensile stress. Stress-strain tendon curves exhibited proportionality between regions. The initial strain, the toe region and the yield point corresponded to the 15, 30 and 70% of the strain failure respectively. INTERPRETATION: Mechanical properties of the lesser-studied human foot tendons are presented under the same test protocol for different engineering and clinical applications. The tendons that work at the inversion/eversion plane are more deformable at the same stress and strain rate than those that work at the flexion/extension plane. PMID- 27280324 TI - Influence of a knee brace intervention on perceived pain and patellofemoral loading in recreational athletes. AB - BACKGROUND: The current investigation aimed to investigate the effects of an intervention using knee bracing on pain symptoms and patellofemoral loading in male and female recreational athletes. METHODS: Twenty participants (11 males & 9 females) with patellofemoral pain were provided with a knee brace which they wore for a period of 2weeks. Lower extremity kinematics and patellofemoral loading were obtained during three sport specific tasks, jog, cut and single leg hop. In addition their self-reported knee pain scores were examined using the Knee injury and Osteoarthritis Outcome Score. Data were collected before and after wearing the knee brace for 2weeks. FINDINGS: Significant reductions were found in the run and cut movements for peak patellofemoral force/pressure and in all movements for the peak knee abduction moment when wearing the brace. Significant improvements were also shown for Knee injury and Osteoarthritis Outcome Score subscale symptoms (pre: male=70.27, female=73.22 & post: male=85.64, female=82.44), pain (pre: male=72.36, female=78.89 & post: male=85.73, female=84.20), sport (pre: male=60.18, female=59.33 & post: male=80.91, female=79.11), function and daily living (pre: male=82.18, female=86.00 & post: male=88.91, female=90.00) and quality of life (pre: male=51.27, female=54.89 & post: male=69.36, female=66.89). INTERPRETATION: Male and female recreational athletes who suffer from patellofemoral pain can be advised to utilise knee bracing as a conservative method to reduce pain symptoms. PMID- 27280325 TI - The influence of passive-dynamic ankle-foot orthosis bending axis location on gait performance in individuals with lower-limb impairments. AB - BACKGROUND: Passive-dynamic ankle-foot orthoses are commonly prescribed to augment impaired ankle muscle function, however their design and prescription are largely qualitative. One design includes a footplate and cuff, and flexible strut connecting the two. During gait, deflection occurs along the strut, with the greatest deflection at a central bending axis. The vertical location of the axis can affect lower extremity biomechanics. The goal of this study was to investigate the influence of bending axis location on gait performance. METHODS: For thirteen participants with unilateral ankle muscle weakness, an additive manufacturing framework was used to fabricate passive-dynamic ankle-foot orthosis struts with central and off-center bending axes. Participants walked overground while electromyographic, kinetic and kinematic data were collected for three different bending axes: proximal (high), central (middle) and distal (low), and the participants indicated their order of bending axis preference after testing. Gait measures and preference effect sizes were examined during six regions of the gait cycle. FINDINGS: A few differences between bending axes were observed: in the first double-leg support peak plantarflexion angle, peak dorsiflexion moment and positive hip work, in the early single-leg support peak knee extension moment and positive ankle and knee work, and in the late single-leg support gastrocnemius activity and vertical ground reaction force impulse. In addition, preference was strongly related to various gait measures. INTERPRETATION: Despite the observed statistical differences, altering bending axis location did not produce large and consistent changes in gait performance. Thus, individual preference and comfort may be more important factors guiding prescription. PMID- 27280326 TI - Dynamical Observation and Detailed Description of Catalysts under Strong Metal Support Interaction. AB - Understanding the structures of catalysts under realistic conditions with atomic precision is crucial to design better materials for challenging transformations. Under reducing conditions, certain reducible supports migrate onto supported metallic particles and create strong metal-support states that drastically change the reactivity of the systems. The details of this process are still unclear and preclude its thorough exploitation. Here, we report an atomic description of a palladium/titania (Pd/TiO2) system by combining state-of-the-art in situ transmission electron microscopy and density functional theory (DFT) calculations with structurally defined materials, in which we visualize the formation of the overlayers at the atomic scale under atmospheric pressure and high temperature. We show that an amorphous reduced titania layer is formed at low temperatures, and that crystallization of the layer into either mono- or bilayer structures is dictated by the reaction environment and predicted by theory. Furthermore, it occurs in combination with a dramatic reshaping of the metallic surface facets. PMID- 27280327 TI - Determination of rifampicin in human plasma by high-performance liquid chromatography coupled with ultraviolet detection after automatized solid-liquid extraction. AB - A precise and accurate high-performance liquid chromatography (HPLC) quantification method of rifampicin in human plasma was developed and validated using ultraviolet detection after an automatized solid-phase extraction. The method was validated with respect to selectivity, extraction recovery, linearity, intra- and inter-day precision, accuracy, lower limit of quantification and stability. Chromatographic separation was performed on a Chromolith RP8 column using a mixture of 0.05 m acetate buffer pH 5.7-acetonitrile (35:65, v/v) as mobile phase. The compounds were detected at a wavelength of 335 nm with a lower limit of quantification of 0.05 mg/L in human plasma. Retention times for rifampicin and 6,7-dimethyl-2,3-di(2-pyridyl) quinoxaline used as internal standard were respectively 3.77 and 4.81 min. This robust and exact method was successfully applied in routine for therapeutic drug monitoring in patients treated with rifampicin. PMID- 27280329 TI - Editorial Comment. PMID- 27280328 TI - Pediatric-Collaborative Health Outcomes Information Registry (Peds-CHOIR): a learning health system to guide pediatric pain research and treatment. AB - The pediatric adaptation of the Collaborative Health Outcomes Information Registry (Peds-CHOIR) is a free, open-source, flexible learning health care system (LHS) that meets the call by the Institute of Medicine for the development of national registries to guide research and precision pain medicine. This report is a technical account of the first application of Peds-CHOIR with 3 aims: (1) to describe the design and implementation process of the LHS; (2) to highlight how the clinical system concurrently cultivates a research platform rich in breadth (eg, clinic characteristics) and depth (eg, unique patient- and caregiver reporting patterns); and (3) to demonstrate the utility of capturing patient caregiver dyad data in real time, with dynamic outcomes tracking that informs clinical decisions and delivery of treatments. Technical, financial, and systems based considerations of Peds-CHOIR are discussed. Cross-sectional retrospective data from patients with chronic pain (N = 352; range, 8-17 years; mean, 13.9 years) and their caregivers are reported, including National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) domains (mobility, pain interference, fatigue, peer relations, anxiety, and depression) and the Pain Catastrophizing Scale. Consistent with the literature, analyses of initial visits revealed impairments across physical, psychological, and social domains. Patients and caregivers evidenced agreement in observable variables (mobility); however, caregivers consistently endorsed greater impairment regarding internal experiences (pain interference, fatigue, peer relations, anxiety, and depression) than patients' self-report. A platform like Peds-CHOIR highlights predictors of chronic pain outcomes on a group level and facilitates individually tailored treatment(s). Challenges of implementation and future directions are discussed. PMID- 27280330 TI - Commentary: Mediation Analyses in the Real World. PMID- 27280331 TI - Comparing Alternative Effect Decomposition Methods: The Role of Literacy in Mediating Educational Effects on Mortality. AB - BACKGROUND: Inverse odds ratio weighting, a newly proposed tool to evaluate mediation in exposure-disease associations, may be valuable for a host of research questions, but little is known about its performance in real data. We compare this approach to a more conventional Baron and Kenny type of decomposition on an additive hazards scale to estimate total, direct, and indirect effects using the example of the role of literacy in mediating the effects of education on mortality. METHODS: Health and Retirement Study participants born in the United States between 1900 and 1947 were interviewed biennially for up to 12 years (N = 17,054). Literacy was measured with a brief vocabulary assessment. Decomposition estimates were derived based on Aalen additive hazards models. RESULTS: A 1 standard deviation difference in educational attainment (3 years) was associated with 6.7 fewer deaths per 1000 person-years (beta = -6.7, 95% confidence interval [CI]: -7.9, -5.4). Of this decrease, 1.3 fewer deaths (beta = -1.3, 95% CI: -4.0, 1.2) were attributed to the literacy pathway (natural indirect), representing 19% of the total effect. Baron and Kenny estimates were consistent with inverse odds ratio weighting estimates but were less variable (natural indirect effect: -1.2 [95% CI: -1.7, 0.69], representing 18% of total effect). CONCLUSION: In a cohort of older Americans, literacy partially mediated the effect of education on mortality. See Video Abstract at http://links.lww.com/EDE/B78. PMID- 27280332 TI - The influence of infant characteristics and attention to social cues on early vocabulary. AB - Individual differences in early language development are related to a number of infant characteristics and skills, including temperament traits, cognitive ability, and social cognition. The current study aimed to assess the complex mechanisms underlying these relations by evaluating the ability to use social cues in a word-learning context along with temperament, cognitive ability, and expressive vocabulary in 71 18-month-old infants. A moderated mediation analysis indicated that infants' nonverbal cognitive ability affects their early vocabulary through its effect on their ability to use social cues, but only in infants with low nonverbal cognitive ability. Implications for both typical and atypical development are discussed. PMID- 27280333 TI - Development of a promoter shutoff system in Aspergillus oryzae using a sorbitol sensitive promoter. AB - Promoter shutoff is a general method for analyzing essential genes, but in the fungus Aspergillus oryzae, no tightly repressed promoters have been reported. To overcome the current limitations of conditional promoters, we examined sorbitol- and galactose-responsive genes using microarrays to identify regulatable genes with only minor physiological and genetic effects. We identified two sorbitol induced genes (designated as sorA and sorB), cloned their promoters, and built a regulated egfp and brlA expression system. Growth medium-dependent enhanced green fluorescence protein (EGFP) fluorescence and conidiation were confirmed for egfp and brlA under the control of their respective promoters. We also used this shutoff system to regulate the essential rhoA, which demonstrated the expected growth inhibition under repressed growth conditions. Our new sorbitol promoter shutoff system developed can serve as a valuable new tool for essential gene analyses of filamentous fungi. PMID- 27280335 TI - Hydrogen Sulfide Triggered Charge-Reversal Micelles for Cancer-Targeted Drug Delivery and Imaging. AB - Currently, the development of polymeric micelles combining diagnosis and targeted therapy is theoretically and practically significant in cancer treatment. In addition, it has been reported that cancer cells can produce large amounts of hydrogen sulfide (H2S) and their survival depends on the content of H2S. In this study, a series of N-(2-hydroxyethyl)-4-azide-1,8-naphthalimide ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-poly(methyl methacrylate) (N3-Nap-PHEMA-b-PMMA-N3) micelles were prepared. Around cancer tissues, the N3-Nap-PHEMA45-b-PMMA42-N3 micelles exhibited dual characteristics of monitoring H2S and H2S triggered charge reversal with the reduction of the azido group. The surface charge of N3-Nap-PHEMA45-b-PMMA42-N3 micelles reversed from negative to positive after monitoring H2S. With H2S triggered charge reversal, the cellular uptake of DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles was effectively enhanced through electrostatic attraction mediated targeting, and a fast doxorubicin (DOX) release rate was observed. The MTT assay demonstrated that N3-Nap-PHEMA45-b-PMMA42-N3 micelles were biocompatible to HeLa cells, and DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles showed enhanced cytotoxicity in HeLa cells in the presence of H2S. Furthermore, in vivo fluorescence imaging and biodistribution experiments revealed that DOX-loaded N3-Nap-PHEMA45-b-PMMA42-N3 micelles could provide good tumor imaging and accumulate in tumor tissue. Therefore, N3-Nap-PHEMA45-b-PMMA42-N3 micelles can be used as a promising platform for tumor diagnosis and therapy. PMID- 27280334 TI - Association of a type 2 diabetes genetic risk score with insulin secretion modulated by insulin sensitivity among Chinese Hans. AB - Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion. The present study aimed to identify the influence of insulin sensitivity on the genetic risk of impaired insulin secretion among a Chinese Han population. For 3229 controls and 1994 treatment-naive T2D, single nucleotide polymorphisms (SNPs) from 24 T2D-related genomic loci were genotyped and a genetic risk score (GRS) was constructed. Results showed that GRS was associated with insulin secretion and disposition indices in both controls and treatment naive T2Ds. Upon stratifying the participants into tertiles by the Matsuda index, we observed an inhibitory relationship between the GRS and insulin secretion in low insulin sensitive but not in high insulin sensitive controls and treatment naive T2Ds. Moreover, low insulin sensitive individuals exhibited more severe impairment in insulin secretion and beta cell response to insulin sensitivity with an increase in risk alleles. Our findings identified that the association of GRS with insulin secretion was strongly modulated by insulin sensitivity in both controls and T2Ds of Chinese Han. It indicates that insulin sensitization should be emphasized in prevention and treatment of T2D for beta cell protection. PMID- 27280336 TI - Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes. AB - Kinetic resolution of nitroallylic amines was established using chiral alpha,alpha-l-diphenylprolinol silyl ether auxiliary through isolation of the dihydrooxazine N-oxide intermediates. Further hydrolyzing the resting states provided tetrahydropyridines in high chemical yields and high to excellent stereoselectivities (up to >20:1 dr and 98% ee). A detailed mechanistic explanation for stereoselective protonation in the dihydrooxazine was probed computationally. In addition, the probable intermediates in alpha-halogenation of aldehydes (masked with enamines) were isolated to provide crystallographic evidence. PMID- 27280337 TI - Clinical characteristics and outcomes of pediatric patients with CMV DNA detection in bronchoalveolar lavage fluid. AB - INTRODUCTION: Cytomegalovirus (CMV) infection can cause severe pulmonary disease in immunocompromised patients. There are no standard diagnostic criteria for CMV pulmonary disease beyond histopathology findings on lung tissue, which is challenging to obtain in pediatric patients. Bronchoalveolar lavage (BAL) fluid is easier to obtain. Since CMV remains latent after primary infection and can potentially reactivate due to any inflammatory response, CMV detection in BAL specimen may not indicate acute CMV pulmonary disease. Thus, we describe the clinical manifestations and outcomes of pediatric patients with CMV detection in BAL fluid. METHODS: We reviewed the clinical, radiologic, and laboratory data of patients <19 years old with a BAL specimen positive for CMV during a 5-year period. RESULTS: Thirty-four encounters in 29 patients were found with CMV detected in their BAL specimen. Half (17/34) of the encounters were in immunocompromised patients. CMV, polymerase chain reaction (PCR) was the most common positive test. Forty-seven percent of the patients had other infections detected in BAL specimens. The majority of patients were never treated for CMV and resolved their acute respiratory illness. Only one patient had probable CMV pulmonary disease. DISCUSSION: CMV is frequently recovered from BAL specimens but does not usually indicate acute CMV pulmonary disease. We would suggest that other diagnoses be considered first, even if CMV is recovered. Pediatr Pulmonol. 2017;52:112-118. (c) 2016 Wiley Periodicals, Inc. PMID- 27280338 TI - Effect of warming and flow rate conditions of blood warmers on red blood cell integrity. AB - BACKGROUND AND OBJECTIVES: Fluid warmers are routinely used to reduce the risk of hypothermia and cardiac complications associated with the infusion of cold blood products. However, warming blood products could generate haemolysis. This study was undertaken to compare the impact of temperature of blood warmers on the per cent haemolysis of packed red blood cells (RBCs) heated at different flow rates as well as non-flow conditions. MATERIALS AND METHODS: Infusion warmers used were calibrated at 41.5 degrees C +/- 0.5 degrees C and 37.5 degrees C +/- 0.5 degrees C. Cold RBC units stored at 4 degrees C in AS-3 (n = 30), aged 30-39 days old, were divided into half units before being allocated under two different scenarios (i.e. infusion pump or syringe). RESULTS: Blood warmers were effective to warm cold RBCs to 37.5 degrees C or 41.5 degrees C when used in conjunction with an infusion pump at flow rate up to 600 ml/h. However, when the warmed blood was held in a syringe for various periods of time, such as may occur in neonatal transfusions, the final temperature was below the expected requirements with measurement as low as 33.1 degrees C. Increasing the flow with an infusion pump increased haemolysis in RBCs from 0.2% to up to 2.1% at a flow rate of 600 ml/h regardless of the warming device used (P < 0.05). No relevant increase of haemolysis was observed using a syringe. CONCLUSIONS: The use of a blood warmer adjusted to 41.5 degrees C is probably the best choice for reducing the risk of hypothermia for the patient without generating haemolysis. However, we should be cautious with the use of an infusion pump for RBC transfusion, particularly at high flow rates. PMID- 27280339 TI - Triphenylphosphonium Decorated Liposomes and Dendritic Polymers: Prospective Second Generation Drug Delivery Systems for Targeting Mitochondria. AB - Targeting specific intracellular organelles has been a biological process of significant interest. Specifically, for mitochondrial targeting, conventional liposomal and dendritic polymer nanoparticles were selected to be presented in this miniperspective. Both types of nanoparticles were decorated on their external surface with triphenylphosphonium cation (TPP), a well-known and effective mitochondrial targeting moiety. Due to their advantageous specificity toward mitochondria, these nanoparticles may be considered as prospective second generation drug delivery systems (DDSs). Functionalized liposomal and dendritic nanoparticles are conveniently prepared, and although they encounter several hurdles on their route from the extracellular environment to the interior of mitochondria, they manage to be accumulated inside them in experiments in vitro. Therefore, the TPP-functionalized nanoparticles presented in this miniperspective can prove effective DDSs and efforts should be continued to obtain results that will trigger further studies including clinical studies, hopefully leading to effective drugs for mitochondrial diseases. In fact, since these DDSs enter and act at the site where the dysfunction exists, a new medicine subspecialty is emerging, the so-called mitochondrial medicine. PMID- 27280340 TI - A Multimedia Fate Model to Support Chemical Management in China: A Case Study for Selected Trace Organics. AB - SESAMe v3.3, a spatially explicit multimedia fate model for China, is a tool suggested to support quantitative risk assessment for national scale chemical management. The key advantage over the previous version SESAMe v3.0 is consideration of spatially varied environmental pH. We evaluate the model performance using estimates of emission from total industry usage of three UV filters (benzophenone-3, octocrylene, and octyl methoxycinnamate) and three antimicrobials (triclosan, triclocarban, and climbazole). The model generally performs well for the six case study chemicals as shown by the comparison between predictions and measurements. The importance of accounting for chemical ionization is demonstrated with the fate and partitioning of both triclosan and climbazole sensitivity to environmental pH. The model predicts ionizable chemicals (triclosan, climbazole, benzophenone-3) to primarily partition into soils at steady state, despite hypothetically only being released to freshwaters, as a result of agricultural irrigation by freshwater. However, further model calibration is needed when more field data becomes available for soils and sediments and for larger areas of water. As an example, accounting for the effect of pH in the environmental risk assessment of triclosan, limited freshwater areas (0.03% or ca. 55 km(2)) in mainland China are modeled to exceed its conservative environmental no-effect threshold. SESAMe v3.3 can be used to support the development of chemical risk assessment methodologies with the spatial aspects of the model providing a guide to the identification regions of interest in which to focus monitoring campaigns or develop a refined risk assessment. PMID- 27280341 TI - Comparison of planned menus and centre characteristics with foods and beverages served in New York City child-care centres. AB - OBJECTIVE: The present study evaluated the extent to which child-care centre menus prepared in advance correspond with food and beverage items served to children. The authors identified centre and staff characteristics that were associated with matches between menus and what was served. DESIGN: Menus were collected from ninety-five centres in New York City (NYC). Direct observation of foods and beverages served to children were conducted during 524 meal and snack times at these centres between April and June 2010, as part of a larger study designed to determine compliance of child-care centres with city health department regulations for nutrition. SETTING: Child-care centres were located in low-income neighbourhoods in NYC. RESULTS: Overall, 87 % of the foods and beverages listed on the menus or allowed as substitutions were served. Menu items matched with foods and beverages served for all major food groups by >60 %. Sweets and water had lower match percentages (40 and 32 %, respectively), but water was served 68 % of the time when it was not listed on the menu. The staff person making the food and purchasing decisions predicted the match between the planned or substituted items on the menus and the foods and beverages served. CONCLUSIONS: In the present study, child-care centre menus included most foods and beverages served to children. Menus planned in advance have potential to be used to inform parents about which child-care centre to send their child or what foods and beverages their enrolled children will be offered throughout the day. PMID- 27280342 TI - ACTINOMYCES NEUII ENDOPHTHALMITIS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION. AB - PURPOSE: To describe a case of acute endophthalmitis caused by Actinomyces neuii after intravitreal anti-vascular endothelial growth factor injection. METHODS: Observational case report, review of published literature. RESULTS: A 67-year-old white man with wet age-related macular degeneration developed endophthalmitis secondary to A. neuii on the 10th day after intravitreal anti-vascular endothelial growth factor injection. Both anterior chamber and vitreous cultures were positive for A. neuii. He was treated successfully with intravitreal injection of vancomycin and ceftazidime. CONCLUSION: This is the first published report of culture-positive endophthalmitis caused by A. neuii after intravitreal injection. PMID- 27280344 TI - Erratum to: Effects of mands on instructional control: A laboratory simulation. AB - [This corrects the article DOI: 10.1007/s40616-014-0015-x.]. PMID- 27280345 TI - A Simple Modification to the Mosquito Homogenization Protocol Safely Inactivates West Nile Virus and Allows Virus Detection by the Rapid Analyte Measurement Platform (RAMP(r)) ASSAY. AB - We evaluated the ability of the Rapid Analyte Measurement Platform (RAMP((r))) mosquito-grinding buffer to inactivate West Nile virus (WNV) by subjecting WNV positive samples ground in RAMP buffer to incubation intervals ranging from 5 min to 60 min. At each time point an aliquot was removed and serially diluted in bovine albumin (BA)-1 cell culture media to stop the inactivation process by RAMP buffer. Each BA-1 sample was tested for viable virus using Vero 6-well cell culture plaque assay and observed for plaques. We observed very limited inactivation of WNV (1-2 log10 plaque-forming units/ml) by RAMP buffer. Concerned for RAMP operators who may be using this assay in low-level biocontainment facilities, we developed an alternate sample homogenization protocol using Triton X-100 detergent that ensures complete WNV inactivation without compromising the performance of the RAMP assay. PMID- 27280346 TI - Mosquitoes in Moose Country: A Mosquito Survey of Northern Minnesota. AB - An adult mosquito survey was conducted at 12 sites using carbon dioxide traps in northern Minnesota throughout the summer of 2012. Specimens were counted, identified to species, sorted into pools, and tested for eastern equine encephalitis (EEEV) and West Nile virus (WNV). Our findings extend the known range of Culiseta melanura, Anopheles barberi, and An. quadrimaculatus and document the presence and abundance of 27 other mosquito taxa in the region. None of the pools tested positive for EEEV or WNV. PMID- 27280347 TI - Large-Volume Gravid Traps Enhance Collection of Culex Vectors. AB - Gravid mosquito collections were compared among several large-volume (infusion volume >=35 liters) gravid trap designs and the small-volume (infusion volume = 6 liters) Centers for Disease Control and Prevention (CDC) gravid trap used routinely by vector control districts for vector and pathogen surveillance. The numbers of gravid Culex quinquefasciatus, Cx. tarsalis, and Cx. stigmatosoma collected by large gravid traps were greater than by the CDC gravid trap during nearly all overnight trials. Large-volume gravid traps collected on average 6.6 fold more adult female Culex mosquitoes compared to small-volume CDC gravid traps across 3 seasons during the 3 years of the studies. The differences in gravid mosquito collections between large-versus small-volume gravid traps were greatest during spring, when 8- to 56-fold more Culex individuals were collected using large-volume gravid traps. The proportion of gravid females in collections did not differ appreciably among the more effective trap designs tested. Important determinants of gravid trap performance were infusion container size and type as well as infusion volume, which determined the distance between the suction trap and the infusion surface. Of lesser importance for gravid trap performance were the number of suction traps, method of suction trap mounting, and infusion concentration. Fermentation of infusions between 1 and 4 wk weakly affected total mosquito collections, with Cx. stigmatosoma collections moderately enhanced by comparatively young and organically enriched infusions. A suction trap mounted above 100 liters of organic infusion housed in a 121-liter black plastic container collected the most gravid mosquitoes over the greatest range of experimental conditions, and a 35-liter infusion with side-mounted suction traps was a promising lesser-volume alternative design. PMID- 27280348 TI - Comparative Field Evaluation of Different Traps for Collecting Adult Phlebotomine Sand Flies (Diptera: Psychodidae) in an Endemic Area of Cutaneous Leishmaniasis in Quintana Roo, Mexico. AB - Phlebotominae are the vectors of Leishmania parasites. It is important to have available surveillance and collection methods for the sand fly vectors. The objectives of the present study were to evaluate and compare traps for the collection of sand fly species and to analyze trap catches along months and transects. Field evaluations over a year were conducted in an endemic area of leishmaniasis in the state of Quintana Roo, Mexico. A randomized-block design was implemented in study area with tropical rainforest vegetation. The study design utilized 4 transects with 11 trap types: 1) Centers for Disease Control and Prevention (CDC) light trap with incandescent bulb (CDC-I), 2) CDC light trap with blue light-emitting diodes (LEDs) (CDC-B), 3) CDC light trap with white LEDs (CDC-W), 4) CDC light trap with red LEDs (CDC-R), 5) CDC light trap with green LEDs (CDC-G), 6) Disney trap, 7) Disney trap with white LEDs, 8) sticky panels, 9) sticky panels with white LEDs, 10) delta-like trap, and 11) delta-like trap with white LEDs. A total of 1,014 specimens of 13 species and 2 genera (Lutzomyia and Brumptomyia) were collected. There were significant differences in the mean number of sand flies caught with the 11 traps; CDC-I was (P = 0.0000) more effective than the other traps. Other traps exhibited the following results: CDC W (17.46%), CDC-B (15.68%), CDC-G (14.89%), and CDC-R (14.30%). The relative abundance of different species varied according to trap types used, and the CDC-I trap attracted more specimens of the known vectors of Leishmania spp., such as like Lutzomyia cruciata, Lu. shannoni, and Lu. ovallesi. Disney trap captured more specimens of Lu. olmeca olmeca. Based on abundance and number of species, CDC light traps and Disney traps appeared to be good candidates for use in vector surveillance programs in this endemic area of Mexico. PMID- 27280349 TI - New Candidates for Plant-Based Repellents Against Aedes aegypti. AB - Based on an ethnobotanical study on use for plant species against mosquito bites in the Kota Tinggi District, Johor State, Malaysia, 3 plants selected for study, Citrus aurantifolia (leaves), Citrus grandis (fruit peel), and Alpinia galanga (rhizome), were extracted using hydrodistillation to produce essential oils. These essential oils were then formulated as a lotion using a microencapsulation process and then tested for their repellent effect against Aedes aegypti. N,N diethyl-m-toluamide (deet) was also prepared in the same formulation and tested for repellency as controls. Four commercial plant-based repellent (KAPS((r)), MozAway((r)), BioZ Natural((r)), and Mosiquard((r))) also were incorporated in the bioassay for comparison purposes. Bioassays revealed that at 20% concentration all repellent formulations demonstrated complete protection for 2 h and >90% for 4 h post-application. The A. galanga-based formulation provided the greatest level of protection (98.91%), which extended for 4 h post-application and was not significantly different from deet at similar concentration. When compared with commercial plant-based repellents (KAPS((r)), MozAway((r)), and BioZ Natural((r))), the 3 lotion formulations showed significantly better protection against Ae. aegypti bites, providing >90% protection for 4 h. In conclusion, our 3 plant-based lotion formulations provided acceptable levels of protection against host-seeking Ae. aegypti and should be developed. PMID- 27280350 TI - Evaluation of Endod (Phytolacca dodecandra: Phytolaccaceae) as a Larvicide Against Anopheles arabiensis, the Principal Vector of Malaria in Ethiopia. AB - Malaria control methods rely mostly on adult mosquito control using insecticide treated nets and indoor residual spraying with insecticides. Plants such as endod (Phytolacca dodecandra) can potentially be used for the control of mosquito larvae as a supplement to adult control methods. Following the discovery of endod, a molluscicide plant, more than 5 decades ago in Ethiopia, subsequent studies have shown that its potency can further be increased by simple procedures such as aging endod berry powder in water. This study was conducted to evaluate the killing effect of fresh and aged endod solution against 4th-stage larvae of Anopheles arabiensis. Laboratory-reared An. arabiensis larvae exposed to different concentrations of endod preparation using distilled or spring water had 50% lethal concentration (LC(50)) = 49.6 ppm and 90% lethal concentration (LC(90)) = 234 ppm for fresh and LC(50) = 36.4 ppm and LC(90) = 115.7 ppm for the aged endod solution in distilled water against the laboratory population. Against field-collected larvae of the same species, aged preparations in habitat water resulted in higher LC(50) (472.7 ppm) and LC(90) (691 ppm) values, with only a slight improvement over fresh preparations in habitat water (LC(50) = 456.2 ppm; LC(90) = 896.1 ppm). In general, although aged preparations of endod required lower concentrations than fresh to kill at least 90% of the larvae, these concentrations were much higher (12-70*) than that required for schistosome transmitting snails. PMID- 27280351 TI - Semi-Field Evaluation of Metofluthrin-Impregnated Nets on Host-Seeking Aedes aegypti and Anopheles dirus. AB - The efficacy of a metofluthrin-impregnated net (MIN) known as the "Mushikonazu" on the house entry behavior of female Aedes aegypti and Anopheles dirus mosquitoes was evaluated using a semi-field 50-m tunnel setup. While the MIN is labeled for the control of chironomids and moth flies, this study determined the feasibility of using the device, given its current construction and metofluthrin formulation, as a spatial repellent against mosquitoes. Sentinel and cone bioassays were used to determine the insecticidal effect of the MIN. A spatial activity index (SAI) was calculated to evaluate responses of the mosquitoes. For the spatial repellent evaluation against Ae. aegypti, the overall mean of SAI was slightly less than 0 at wk 1 after the MIN application and then decreased for the last 4 wk showing a preference to treatment tent. For An. dirus, the mean SAI at wk 1 was positive, indicating a presumed repellent effect of the MIN against An. dirus. For the subsequent 4 wk, the SAI was negative, indicating a preference for the MIN. Results suggested that the MIN may not be a promising approach to repel Ae. aegypti and An. dirus under field conditions in Thailand. However, it remains probable that the MIN may be effective as a spatial repellent if modifications are made to the metofluthrin concentration or formulation and/or the construction of the device. PMID- 27280352 TI - Evaluation of Alternative Methods for Testing the Bioefficacy of Household Ambient Insecticide Products Against Aedes albopictus. AB - Ambient insecticides are receiving increasing attention in many developed countries because of their value in reducing mosquito nuisance. As required by the European Union Biocidal Products Regulation 528/2012, these devices require appropriate testing of their efficacy, which is based on estimating the knockdown and mortality rates of free-flying (free) mosquitoes in a test room. However, evaluations using free mosquitoes present many complexities. The performances of 6 alternative methods with mosquitoes held in 2 different cage designs (steel wire and gauze/plastic) with and without an operating fan for air circulation were monitored in a test room through a closed-circuit television system and were compared with the currently recommended method using free mosquitoes. Results for caged mosquitoes without a fan showed a clearly delayed knockdown effect, whereas outcomes for caged mosquitoes with a fan recorded higher mortality at 24 h, compared to free mosquitoes. Among the 6 methods, cages made of gauze and plastic operating with fan wind speed at 2.5-2.8 m/sec was the only method without a significant difference in results for free mosquitoes, and therefore appears as the best alternative to assess knockdown by ambient insecticides accurately. PMID- 27280353 TI - Multiple-Insecticide Resistance and Classic Gene Mutations to Japanese Encephalitis Vector Culex tritaeniorhynchus from China. AB - Widespread resistance of insect pests to insecticides has been widely reported in China and there is consequently an urgent need to adjust pest management strategies appropriately. This requires detailed information on the extent and causes of resistance. The aim of the present study was to investigate levels of resistance to 5 insecticides among 12 strains of Culex tritaeniorhynchus, a major vector of Japanese encephalitis in China. Resistance to deltamethrin, beta cypermethrin, permethrin, dichlorvos, and propoxur were measured using larval bioassays. The allelic frequency of knockdown resistance (kdr) and acetylcholinesterase (AChE) mutations were determined in all strains. Larval bioassay results indicated that the field strains collected from different sites were resistant to deltamethrin, beta-cypermethrin, permethrin, dichlorvos, and propoxur, with resistance ratio values ranging from 1.70- to 71.98-fold, 7.83- to 43.07-fold, 3.54- to 40.03-fold, 291.85- to 530.89-fold, and 51.32- to 108.83 fold, respectively. A polymerase chain reaction amplification of specific alleles method for individual was developed to detect genotypes of the AChE gene mutation F455W in Cx. tritaeniorhynchus. The frequency of the AChE gene mutation F455W was 100.00% in all strains, making this mutation of no value as a marker of resistance to organophosphorous and carbamate pesticides in Cx. tritaeniorhynchus in China. The kdr allele was present in all strains at frequencies of 10.00 29.55%. Regression analysis indicated a significant correlation between kdr allele frequencies and levels of resistance to deltamethrin, beta-cypermethrin, and permethrin. These results highlight the need to monitor and map insecticide resistance in Cx. tritaeniorhynchus and to adjust pesticide use to minimize the development of resistance in these mosquitoes. PMID- 27280354 TI - Updated Bionomics of Toxorhynchites aurifluus and Toxorhynchites manicatus in Taiwan. AB - The larvae of the genus Toxorhynchites are typically found in sylvatic habitat environments. They have been proposed as potential biocontrol agents against disease vectors such as Aedes, specifically the larvae of Ae. aegypti and Ae. albopictus. The only 2 species of Toxorhynchites identified in Taiwan are Tx. aurifluus and Tx. manicatus, but there have been no published records of either species since 1984. In January 2014, we identified 2 4th-stage Tx. aurifluus larvae and 2 4th-stage Tx. manicatus larvae in artificial habitats close to dwellings in Guichong village, Pingtung County, Taiwan. Here we update the bionomics of the larvae of both species, including coexisting aquatic fauna, the physicochemical parameters of the larval habitats, and developmental time. We further compare the findings with past records. PMID- 27280355 TI - Oviposition Activity Patterns of Culex pipiens and Culex restuans in Pennsylvania. AB - Culex pipiens and Cx. restuans are the main vectors of West Nile virus and the primary target species of surveillance and control programs in Pennsylvania. Performing adult control, specifically ultra-low volume (ULV) applications, at night during peak oviposition activity time(s) is necessary to control these species. In July and August of 2009, collections were made at 15-min intervals starting at sunset and continuing until 3 h after sunset to establish a more accurate timeline of Cx. pipiens and Cx. restuans oviposition flight activity. The highest numbers of Cx. pipiens and Cx. restuans were collected during the 15 30, 30-45, and 45-60 min postsunset time intervals (P < 0.05). Oviposition activity began to decrease after 60 min postsunset. These observations have identified a smaller oviposition activity period for Cx. pipiens and Cx. restuans than noted from other studies, thus potentially improving the timing of ULV operations to control these 2 vector species. PMID- 27280356 TI - Evaluation of DeltaGard(r) Ground Application Against Aedes albopictus in a Residential Area in St. Augustine, Florida. AB - Aedes albopictus is an invasive species that poses a health threat in many residential neighborhoods throughout Florida. Aedes albopictus is a high priority for mosquito control efforts in the state. The efficacy of DeltaGard((r)) (AI 2% deltamethrin) application against Ae. albopictus was evaluated in a residential area in St. Augustine, FL. DeltaGard was applied using a truck-mounted ultra-low volume aerosol generator along 3 streets in a residential neighborhood. Caged mosquito mortality and droplet density data were recorded. Leaf clippings from houses on treated streets were bioassayed against laboratory-reared Ae. albopictus. Overall, the DeltaGard application was found to be more effective in the front yard of the houses, resulting in 78.3% mortality in caged mosquitoes, 42 % mortality in leaf bioassays, and 50.5 nl/cc in spray density. Based on the amount of vegetation and residential barriers around the houses, the application caused only 46.3% mortality in caged mosquitoes, 7.5% mortality in leaf bioassays, and 5.4 nl/cc in spray density in the back yard sites. PMID- 27280357 TI - Evaluation of Three Commercial Handheld Ultra-Low-Volume Foggers with Aqualure(r) 20-20 Against Adult Aedes albopictus. AB - The Anastasia Mosquito Control District (AMCD) tests all equipment before field use to determine if machines are suitable for the needs of the district. Three handheld ultra-low-volume (ULV) foggers--the American LongRay (ULV) Fogger Model 3600B with rechargeable lithium battery (DC model), American LongRay ULV Fogger Model 3600E with 110V or 220V AC power (AC model), and Boston Fog Battery Motorized Fogger (Boston Fogger)--were compared to determine which fogger would be most suitable for use by AMCD. Mortality of caged Aedes albopictus was analyzed after 24 h to determine the success of a single application. All 3 foggers resulted in 100% mortality after 24 h using the insecticide Aqualuer 20 20 (active ingredients permethrin 20.6% and piperonyl butoxide 20.6%) 1:5 dilution with reverse osmosis water. Based on operator safety, robustness, and operational performance, the American LongRay DC model was found to be the most suitable at administering Aqualuer 20-20 against caged adult Ae. albopictus. PMID- 27280358 TI - Evaluation of a New Thermal Fog Machine for Control of Adult Aedes albopictus in a Large Enclosed Space. AB - Testing of the PSO BASDKA-AC1200 multifunction ultrafine particle atomization machine, a thermal fog machine, with Aqualuer 20-20((r)) (permethrin 20.6%, piperonyl butoxide 20.6%) was conducted against Aedes albopictus. The machine was set at a 40 sec maximum burst interval dispersing 36 ml of chemical with an average droplet volume of 50%. Female adult Ae. albopictus were placed into cylindrical paper cages and adhered to poles at 5, 8, 10, 15, and 25 m from the center point of the machine. Control cages consisted of 1 cage placed at 5, 10, and 25 m. Control and treatment groups were left in the experiment area for 15 min. Initial knockdown after 15 min and 24 h mortality were documented. At 15 min post-treatment, Ae. albopictus displayed less than 50% knockdown. After 24 h, all treatment cages displayed greater than 90% mortality. Further bottle bioassays were conducted to determine the lowest chemical dose possible to achieve a lethal dose of 90%. A 1% dilution (10 ml Aqualuer 20-20 to 1,000 ml of polyether) of Aqualuer showed high mortality in the laboratory. However, after running 3 repetitions of a 1% dilution, there was no significant difference between the mortality of the mosquitoes at any of the distances 24 h post-treatment. This study indicates that the test machine would be an applicable and suitable machine for control of Ae. albopictus in enclosed spaces. PMID- 27280360 TI - Dependability of data derived from time sampling methods with multiple observation targets. AB - In this study, generalizability theory was used to examine the extent to which (a) time-sampling methodology, (b) number of simultaneous behavior targets, and (c) individual raters influenced variance in ratings of academic engagement for an elementary-aged student. Ten graduate-student raters, with an average of 7.20 hr of previous training in systematic direct observation and 58.20 hr of previous direct observation experience, scored 6 videos of student behavior using 12 different time-sampling protocols. Five videos were submitted for analysis, and results for observations using momentary time-sampling and whole-interval recording suggested that the majority of variance was attributable to the rating occasion, although results for partial-interval recording generally demonstrated large residual components comparable with those seen in prior research. Dependability coefficients were above .80 when averaging across 1 to 2 raters using momentary time-sampling, and 2 to 3 raters using whole-interval recording. Ratings derived from partial-interval recording needed to be averaged over 3 to 7 raters to demonstrate dependability coefficients above .80. (PsycINFO Database Record PMID- 27280362 TI - Reconstruction of Fingertip Defects With Great Toe Pulp Grafts: Reply. PMID- 27280361 TI - Spin Crossover in Fe(II) Complexes with N4S2 Coordination. AB - Reactions of Fe(II) precursors with the tetradentate ligand S,S'-bis(2 pyridylmethyl)-1,2-thioethane (bpte) and monodentate NCE(-) coligands afforded mononuclear complexes [Fe(bpte)(NCE)2] (1, E = S; 2, E = Se; 3, E = BH3) that exhibit temperature-induced spin crossover (SCO). As the ligand field strength increases from NCS(-) to NCSe(-) to NCBH3(-), the SCO shifts to higher temperatures. Complex 1 exhibits only a partial (15%) conversion from the high spin (HS) to the low-spin (LS) state, with an onset around 100 K. Complex 3 exhibits a complete SCO with T1/2 = 243 K. While the gamma-2 polymorph also shows the complete SCO with T1/2 = 192 K, the alpha-2 polymorph exhibits a two-step SCO with the first step leading to a 50% HS -> LS conversion with T1/2 = 120 K and the second step proceeding incompletely in the 80-50 K range. The amount of residual HS fraction of alpha-2 that remains below 60 K depends on the cooling rate. Fast flash-cooling allows trapping of as much as 45% of the HS fraction, while slow cooling leads to a 14% residual HS fraction. The slowly cooled sample of alpha-2 was subjected to irradiation in the magnetometer cavity resulting in a light-induced excited spin state trapping (LIESST) effect. As demonstrated by Mossbauer spectroscopy, an HS fraction of up to 85% could be achieved by irradiation at 4.2 K. PMID- 27280363 TI - Comparative Experimental and Computational Study of Monoalkyl Chain Phosphatidylcholine-Containing Thermoresponsive Liposomes. AB - Liposomes containing lysophospholipids are intensively studied as drug delivery systems that are stable at normal body temperature but exhibit fast release of their drug load at slightly elevated temperatures. In this study, the stability and release properties of dipalmitoylglycerophosphocholine (DPPC)-based liposomes incorporating the commonly used lysophosphatidylocholine (lyso-PC), and a series of monoalkyl chain ether-linked phosphatidylcholine, i.e., the biologically relevant monoalkyl chain platelet activating factor (PAF) and its derivatives lyso-PAF and methyl-PAF, were investigated. To this end a series of PEGylated small unilamellar liposomes with DPPC:monoalkyl lipid compositions of 5% and 10% molar ratio were prepared and compared with regard to stability (37 degrees C) and release properties at elevated temperatures (38-43 degrees C). All systems were characterized with respect to size distribution, zeta-potential, and phase transition characteristics. The presence of ether-lipids endows liposomes with superior (~10% increase) release properties at 5% incorporation compared to lyso PC, while at 10% molar ratio the formulations do not differ significantly, the release being close to 90%. The findings are supported by atomistic molecular dynamics simulations that suggest a correlation between the enhanced permeability and increased penetration of water molecules within the bilayers with density fluctuations resulting from the increased area-per-lipid and the disorder of the lysolipids alkyl chains. PMID- 27280364 TI - Implications of supportive and unsupportive behavior for couples with newly diagnosed diabetes. AB - OBJECTIVE: To examine the relation between daily diary reports of diabetes specific social interactions to patient and partner mood and patient self-care behaviors, and whether relations are moderated by unmitigated communion. METHOD: Participants were 70 couples in which 1 person had been diagnosed with Type 2 diabetes in the past 3 years. They were interviewed in-person at baseline and completed daily diary reports on an iPad. Daily diary questionnaires measured support, mood, and self-care behavior (patients only). Unmitigated communion, a personality trait characterized by an overinvolvement in others to the exclusion of the self, was measured at baseline. RESULTS: Multilevel statistical modeling revealed that daily fluctuations in partner emotional support were related to daily fluctuations in happy mood, more exercise, and dietary compliance. Partner controlling behavior was related to poor mood but was unrelated to self-care. Relations of support and controlling behavior to mood were strongest for individuals high (vs. low) in unmitigated communion. CONCLUSION: Patients newly diagnosed with Type 2 diabetes who felt understood and cared for by partners reported a better mood and were more likely to take care of themselves on a daily basis, whereas patients whose partners were controlling on a daily basis reported poorer mood. Patients characterized by unmitigated communion were most affected by partner supportive and unsupportive behavior. (PsycINFO Database Record PMID- 27280365 TI - The impact of changing attitudes, norms, and self-efficacy on health-related intentions and behavior: A meta-analysis. AB - OBJECTIVE: Several health behavior theories converge on the hypothesis that attitudes, norms, and self-efficacy are important determinants of intentions and behavior. However, inferences regarding the relation between these cognitions and intention or behavior rest largely on correlational data that preclude causal inferences. To determine whether changing attitudes, norms, or self-efficacy leads to changes in intentions and behavior, investigators need to randomly assign participants to a treatment that significantly increases the respective cognition relative to a control condition, and test for differences in subsequent intentions or behavior. The present review analyzed findings from 204 experimental tests that met these criteria. METHOD: Studies were located using computerized searches and informal sources and meta-analyzed using STATA Version 11. RESULTS: Experimentally induced changes in attitudes, norms, and self efficacy all led to medium-sized changes in intention (d+ = .48, .49, and .51, respectively), and engendered small to medium-sized changes in behavior (attitudes-d+ = .38, norms-d+ = .36, self-efficacy-d+ = .47). These effect sizes generally were not qualified by the moderator variables examined (e.g., study quality, theoretical basis of the intervention, methodological characteristics, and features of the targeted behavior), although effects were larger for interventions designed to increase (vs. decrease) behavioral performance. CONCLUSION: The present review lends novel, experimental support for key predictions from health behavior theories, and demonstrates that interventions that modify attitudes, norms, and self-efficacy are effective in promoting health behavior change. (PsycINFO Database Record PMID- 27280366 TI - Religious participation predicts diurnal cortisol profiles 10 years later via lower levels of religious struggle. AB - OBJECTIVE: Multiple aspects of religion have been linked with a variety of physical health outcomes; however, rarely have investigators attempted to empirically test the mechanisms through which religiosity impacts health. The links between religious participation, religious coping, and diurnal cortisol patterns over a 10-year period in a national sample of adults in the United States were investigated. METHOD: Participants included 1,470 respondents from the Midlife in the United States (MIDUS) study who provided reports on religious participation, religious coping, and diurnal cortisol. RESULTS: Religious participation predicted steeper ("healthier") cortisol slopes at the 10-year follow-up, controlling for potential confounds. Further, religious struggle (religious coping marked by tension and strain about religious and spiritual issues) mediated the prospective association between religious participation and cortisol slope, such that greater religious attendance predicted lower levels of religious struggle 10 years later, which in turn was linked with a steeper cortisol slope; this effect remained strong when controlling for general emotional coping and social support. Positive religious coping was unrelated to diurnal cortisol patterns. CONCLUSION: These findings identify religious struggle as a mechanism through which religious participation impacts diurnal cortisol levels and suggest that diurnal cortisol is a plausible pathway through which aspects of religion influence long-term physical health. (PsycINFO Database Record PMID- 27280367 TI - Enhancing the effectiveness of alcohol warning labels with a self-affirming implementation intention. AB - OBJECTIVE: Excess alcohol consumption extorts significant social and economic costs that are increasing despite the presence of mandatory warning labels on packaged alcoholic beverages. We used a novel approach by adding a brief statement based on self-affirmation theory to alcohol warning labels. METHOD: In two studies (N = 85 and N = 58), we randomized regular wine drinkers recruited from university campuses to complete a wine-pouring task with bottles that had standard labeling or bottles that added a self-affirming implementation intention to the standard labeling. Alcohol consumption, behavioral intention, and self efficacy were measured premanipulation; message acceptance was measured postmanipulation; and alcohol consumption, behavioral intention, and self efficacy were measured again at follow-up. RESULTS: In both studies, the self affirming implementation intention significantly reduced subsequent alcohol consumption (ds = 0.70 and 0.91, respectively). However, message acceptance, behavioral intention, and self-efficacy did not significantly mediate the observed effects. CONCLUSIONS: Self-affirming implementation intentions augmented the effect of alcohol warning labels to reduce subsequent alcohol consumption, but-consistent with the broader self-affirmation literature-it was not clear what mediated the effects. Further research is required to examine the effects of self affirming implementation intentions on other kinds of public health-related labeling. (PsycINFO Database Record PMID- 27280368 TI - Socioeconomic status, psychological resources, and inflammatory markers: Results from the MIDUS study. AB - OBJECTIVE: Our objective was to investigate interactions of psychological resources and socioeconomic status (SES)-as well as potential gender differences and the explanatory role of childhood and adult stress exposures, health behaviors, and negative and positive affect-in predicting markers of systemic inflammation. METHOD: We utilized a sample of adults from the Midlife Development in the U.S. (MIDUS) study who provided biomarker data (N = 1,152). SES was operationalized as a composite of education, income, and occupational prestige, and the psychological resources construct was operationalized as a latent factor measured with optimism, perceived control, and self-esteem. Linear regression models examined these 2 factors and their interaction in predicting interleukin-6 (IL-6) and C-reactive protein (CRP) measured on average 2 years later, as well as 3-way interactions involving gender and the impact of covariate adjustment. RESULTS: Psychological resources interacted with SES in men (for IL-6: p < .001; for CRP: p = .04) but not in women. In men, greater psychological resources was associated with lower concentrations of IL-6 at lower levels of SES but higher concentrations of both markers at higher levels of SES. The inverse association between resources and IL-6 at low SES was moderately attenuated upon adjustment for negative affect. CONCLUSION: Socioeconomic status might modulate the linkage between psychological resources and systemic inflammation in men. At lower levels of SES, resources may be related to lower inflammation in part through lower negative affect. Associations with higher inflammation at higher SES add to growing evidence suggesting that adaptive psychological characteristics may be associated with markers of poorer physiological function under certain conditions. (PsycINFO Database Record PMID- 27280369 TI - Posttraumatic stress symptomatology and appearance distress following burn injury: An interpretative phenomenological analysis. AB - OBJECTIVES: Although many traumatic incidents result in changes to appearance, little research has examined the experience of individuals distressed by such changes in connection with psychological processes involved in posttraumatic stress disorder (PTSD). This study aimed to examine how PTSD and appearance concern associated with burn injury are experienced when both difficulties co occur. METHOD: The qualitative method of interpretative phenomenological analysis (IPA) was used to provide a framework for building nuanced accounts of individual experience. In-depth analysis was conducted with interview data obtained from 8 women, who were purposively selected on the basis of being distressed in relation to burn scarring, and having symptoms of PTSD. RESULTS: Participants described how changes in appearance were experienced as maintaining a sense of threat through social stigma, and acting as a trigger for re-experiencing the traumatic incident that had caused the burn injury. As such, appearance concern and PTSD symptomatology appeared intertwined within the participants' accounts of their postburn injury recovery. CONCLUSIONS: This is the first study to consider some of the processes through which PTSD and appearance concern might be mutually maintained. The results suggest that psychosocial interventions need to be tailored to simultaneously address processes related to concerns about change in appearance and also with traumatic re-experiencing. (PsycINFO Database Record PMID- 27280370 TI - The impact of negative family-work spillover on diurnal cortisol. AB - OBJECTIVE: Both dimensions of the work-family interface, work-to-family and family-to-work spillover, have important implications for health and well-being. Despite the importance of these associations, very little is known about the physiological mechanisms through which the interplay between family and work experiences are translated into long-lasting consequences for health. METHOD: This study investigated both positive and negative aspects of each spillover dimension on diurnal cortisol secretion patterns in a large panel study of working adults between the ages of 33 and 80. RESULTS: Greater negative family-to work (NFW) spillover predicted lower wake-up cortisol values and a flatter (less "healthy") diurnal cortisol slope. This effect was evident even after controlling for the effects of the other spillover dimensions. CONCLUSIONS: These findings indicate that not all aspects of the work-family interface might impact stress physiology to the same extent and suggest that diurnal cortisol may be an important pathway through which negative aspects of the work-family interface leave their mark on health. (PsycINFO Database Record PMID- 27280371 TI - Major flood related strains and pregnancy outcomes. AB - OBJECTIVE: To assess the impact of experiencing a major flood during pregnancy on fetal growth and length of gestation, and to consider how flood-related strains might contribute to these effects. METHOD: The Red River Pregnancy Project was a prospective study carried out for 3 months immediately after the historic 2009 crest of the Red River in Fargo, North Dakota. Pregnant community residents who were at least 18 years old with a singleton, intrauterine pregnancy participated in the study (N = 169). Analyses examined if birth weight and length of gestation were associated with residential distance from flooding and gestational age at time of the flood crest. RESULTS: For pregnancies earlier in gestation during the crest (-1 SD = 12 weeks), birth weight decreased as distance from flooding decreased (-42.29 g/mi, p < .01). For pregnancies later in gestation at crest (+1 SD = 26 weeks), distance was not associated with birth weight (p > .10). Biparietal growth trajectories showed a decrease in growth after the crest of the flood but only for women early in pregnancy. However, various measures of flood related and general stress or strain did not explain these effects. Length of gestation was not associated with distance from or the timing of the flood. CONCLUSIONS: Pregnant women in the first trimester who experience a major flood near their homes are at risk of having lower birth weight neonates due to a reduction in fetal growth. The mechanisms of this effect deserve further attention in rapidly mounted investigations after disaster. (PsycINFO Database Record PMID- 27280372 TI - Anticipated regret and organ donor registration: A randomized controlled trial. AB - OBJECTIVE: To test whether simply asking people to rate the extent to which they anticipate feeling regret for not registering as an organ donor after death increases subsequent verified organ donor registration. METHOD: There were 14,509 members of the general public (both registered and nonregistered donors) randomly allocated to 1 of 4 arms, each receiving different questionnaires. The no questionnaire control (NQC) arm received a survey measuring demographics and whether or not they were registered organ donors. The questionnaire control (QC) arm completed the NQC questions plus questions regarding affective attitudes and intention to register as an organ donor. The theory of planned behavior (TPB) questionnaire arm received the QC questionnaire, plus additional items measuring TPB variables. The anticipated regret (AR) arm received the TPB questionnaire, plus 2 additional items measuring anticipated regret. The main outcome measures were number of nondonor participants who subsequently registered 6 months later, as verified by the United Kingdom national transplant register. RESULTS: Intention-to-treat (ITT) analysis in nonregistered donors (N = 9,139) revealed the NQC arm were more likely to register as an organ donor (6.39%) compared with the AR (4.51%) arm. CONCLUSIONS: A brief anticipated regret intervention led to a decrease in registration. A potential reason is discussed in terms of questionnaire item content "priming" negative perceptions of organ donation. This is a methodological concern that needs to be addressed in studies that use similar interventions. Current controlled trials: www.controlled-trials.com number: ISRCTN922048897. (PsycINFO Database Record PMID- 27280373 TI - ENDOCRINOLOGY IN PREGNANCY: Pregnancy and the incidence, diagnosing and therapy of Graves' disease. AB - Thyroid hormones are essential developmental factors, and Graves' disease (GD) may severely complicate a pregnancy. This review describes how pregnancy changes the risk of developing GD, how early pregnancy by several mechanisms leads to considerable changes in the results of the thyroid function tests used to diagnose hyperthyroidism, and how these changes may complicate the diagnosing of GD. Standard therapy of GD in pregnancy is anti-thyroid drugs. However, new studies have shown considerable risk of birth defects if these drugs are used in specific weeks of early pregnancy, and this should be taken into consideration when planning therapy and control of women who may in the future become pregnant. Early pregnancy is a period of major focus in GD, where pregnancy should be diagnosed as soon as possible, and where important and instant change in therapy may be warranted. Such change may be an immediate stop of anti-thyroid drug therapy in patients with a low risk of rapid relapse of hyperthyroidism, or it may be an immediate shift from methimazole/carbimazole (with risk of severe birth defects) to propylthiouracil (with less risk), or maybe to other types of therapy where no risk of birth defects have been observed. In the second half of pregnancy, an important concern is that not only the mother with GD but also her foetus should have normal thyroid function. PMID- 27280374 TI - Acromegaly incidence, prevalence, complications and long-term prognosis: a nationwide cohort study. AB - DESIGN: Valid data on acromegaly incidence, complications and mortality are scarce. The Danish Health Care System enables nationwide studies with complete follow-up and linkage among health-related databases to assess acromegaly incidence, prevalence, complications and mortality in a population-based cohort study. METHOD: All incident cases of acromegaly in Denmark (1991-2010) were identified from health registries and validated by chart review. We estimated the annual incidence rate of acromegaly per 10(6) person-years (py) with 95% confidence intervals (95% CIs). For every patient, 10 persons were sampled from the general population as a comparison cohort. Cox regression and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used. RESULTS: Mean age at diagnosis (48.7 years (CI: 95%: 47.2-50.1)) and annual incidence rate (3.8 cases/10(6) persons (95% CI: 3.6-4.1)) among the 405 cases remained stable. The prevalence in 2010 was 85 cases/10(6) persons. The patients were at increased risk of diabetes mellitus (HR: 4.0 (95% CI: 2.7-5.8)), heart failure (HR: 2.5 (95% CI: 1.4-4.5)), venous thromboembolism (HR: 2.3 (95% CI: 1.1-5.0)), sleep apnoea (HR: 11.7 (95% CI: 7.0-19.4)) and arthropathy (HR: 2.1 (95% CI: 1.6-2.6)). The complication risk was also increased before the diagnosis of acromegaly. Overall mortality risk was elevated (HR: 1.3 (95% CI: 1.0-1.7)) but uninfluenced by treatment modality. CONCLUSION: (i) The incidence rate and age at diagnosis of acromegaly have been stable over decades, and the prevalence is higher than previously reported. (ii) The risk of complications is very high even before the diagnosis. (iii) Mortality risk remains elevated but uninfluenced by mode of treatment. PMID- 27280375 TI - Dissociative Carbon Dioxide Adsorption and Morphological Changes on Cu(100) and Cu(111) at Ambient Pressures. AB - Ambient-pressure X-ray photoelectron spectroscopy (APXPS) and high-pressure scanning tunneling microscopy (HPSTM) were used to study the structure and chemistry of model Cu(100) and Cu(111) catalyst surfaces in the adsorption and dissociation of CO2. It was found that the (100) face is more active in dissociating CO2 than the (111) face. Atomic oxygen formed after the dissociation of CO2 poisons the surface by blocking further adsorption of CO2. This "self poisoning" mechanism explains the need to mix CO into the industrial feed for methanol production from CO2, as it scavenges the chemisorbed O. The HPSTM images show that the (100) surface breaks up into nanoclusters in the presence of CO2 at 20 Torr and above, producing active kink and step sites. If the surface is precovered with atomic oxygen, no such nanoclustering occurs. PMID- 27280378 TI - On the determination of the thermal comfort conditions of a metropolitan city underground railway. AB - Although the indoor thermal comfort concept has received increasing research attention, the vast majority of published work has been focused on the building environment, such as offices, residential and non-residential buildings. The present study aims to investigate the thermal comfort conditions in the unique and complex underground railway environment. Field measurements of air temperature, air humidity, air velocity, globe temperature and the number of passengers were conducted in the modern underground railway of Athens, Greece. Environmental monitoring was performed in the interior of two types of trains (air-conditioned and forced air ventilation cabins) and on selected platforms during the summer period. The thermal comfort was estimated using the PMV (predicted mean vote) and the PPD (predicted percentage dissatisfied) scales. The results reveal that the recommended thermal comfort requirements, although at relatively low percentages are met only in air-conditioned cabins. It is found that only 33% of the PPD values in air-conditioned cabins can be classified in the less restrictive comfort class C, as proposed by ISO-7730. The thermal environment is "slightly warm" in air-conditioned cabins and "warm" in forced air ventilation cabins. In addition, differences of the thermal comfort conditions on the platforms are shown to be associated with the depth and the design characteristics of the stations. The average PMV at the station with small depth is 0.9 scale points higher than that of the station with great depth. The number of passengers who are waiting at the platforms during daytime reveals a U-shaped pattern for a deep level station and an inverted course of PMV for a small depth station. Further, preliminary observations are made on the distribution of air velocity on the platforms and on the impact of air velocity on the thermal comfort conditions. PMID- 27280379 TI - Predicting environmental mitigation requirements for hydropower projects through the integration of biophysical and socio-political geographies. AB - Uncertainty about environmental mitigation needs at existing and proposed hydropower projects makes it difficult for stakeholders to minimize environmental impacts. Hydropower developers and operators desire tools to better anticipate mitigation requirements, while natural resource managers and regulators need tools to evaluate different mitigation scenarios and order effective mitigation. Here we sought to examine the feasibility of using a suite of multi-faceted explanatory variables within a spatially explicit modeling framework to fit predictive models for future environmental mitigation requirements at hydropower projects across the conterminous U.S. Using a database comprised of mitigation requirements from more than 300 hydropower project licenses, we were able to successfully fit models for nearly 50 types of environmental mitigation and to apply the predictive models to a set of more than 500 non-powered dams identified as having hydropower potential. The results demonstrate that mitigation requirements are functions of a range of factors, from biophysical to socio political. Project developers can use these models to inform cost projections and design considerations, while regulators can use the models to more quickly identify likely environmental issues and potential solutions, hopefully resulting in more timely and more effective decisions on environmental mitigation. PMID- 27280380 TI - Gramine Derivatives Targeting Ca(2+) Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases. AB - We describe the synthesis of gramine derivatives and their pharmacological evaluation as multipotent drugs for the treatment of Alzheimer's disease. An innovative multitarget approach is presented, targeting both voltage-gated Ca(2+) channels, classically studied for neurodegenerative diseases, and Ser/Thr phosphatases, which have been marginally aimed, even despite their key role in protein tau dephosphorylation. Twenty-five compounds were synthesized, and mostly their neuroprotective profile exceeded that offered by the head compound gramine. In general, these compounds reduced the entry of Ca(2+) through VGCC, as measured by Fluo-4/AM and patch clamp techniques, and protected in Ca(2+) overload-induced models of neurotoxicity, like glutamate or veratridine exposures. Furthermore, we hypothesize that these compounds decrease tau hyperphosphorylation based on the maintenance of the Ser/Thr phosphatase activity and their neuroprotection against the damage caused by okadaic acid. Hence, we propose this multitarget approach as a new and promising strategy for the treatment of neurodegenerative diseases. PMID- 27280381 TI - Zinc intake, microRNA dysregulation, and esophageal cancer. PMID- 27280382 TI - On the Minimum Error Correction Problem for Haplotype Assembly in Diploid and Polyploid Genomes. AB - In diploid genomes, haplotype assembly is the computational problem of reconstructing the two parental copies, called haplotypes, of each chromosome starting from sequencing reads, called fragments, possibly affected by sequencing errors. Minimum error correction (MEC) is a prominent computational problem for haplotype assembly and, given a set of fragments, aims at reconstructing the two haplotypes by applying the minimum number of base corrections. MEC is computationally hard to solve, but some approximation-based or fixed-parameter approaches have been proved capable of obtaining accurate results on real data. In this work, we expand the current characterization of the computational complexity of MEC from the approximation and the fixed-parameter tractability point of view. In particular, we show that MEC is not approximable within a constant factor, whereas it is approximable within a logarithmic factor in the size of the input. Furthermore, we answer open questions on the fixed-parameter tractability for parameters of classical or practical interest: the total number of corrections and the fragment length. In addition, we present a direct 2 approximation algorithm for a variant of the problem that has also been applied in the framework of clustering data. Finally, since polyploid genomes, such as those of plants and fishes, are composed of more than two copies of the chromosomes, we introduce a novel formulation of MEC, namely the k-ploid MEC problem, that extends the traditional problem to deal with polyploid genomes. We show that the novel formulation is still both computationally hard and hard to approximate. Nonetheless, from the parameterized point of view, we prove that the problem is tractable for parameters of practical interest such as the number of haplotypes and the coverage, or the number of haplotypes and the fragment length. PMID- 27280383 TI - Flavivirus modulation of cellular metabolism. AB - Over the last decade, we have begun to appreciate how flaviviruses manipulate cellular metabolism to establish an optimal environment for their replication. These metabolic changes include the stimulation of glycolysis, in addition to lipid anabolic and catabolic pathways. These processes are thought to promote an energetically favorable state, in addition to modifying membrane lipid composition for viral replication and virion envelopment. Importantly, many of these processes can be pharmacologically inhibited as successful antiviral strategies, at least in cell culture. In this review, we discuss the mechanisms by which flaviviruses alter cellular metabolism, remaining questions, and opportunities for therapeutic development. PMID- 27280384 TI - A multicenter prospective study of the real-time use of narrow-band imaging in the diagnosis of premalignant gastric conditions and lesions. AB - BACKGROUND AND AIM: Some studies suggest that narrow-band imaging (NBI) can be more accurate at diagnosing gastric intestinal metaplasia and dysplasia than white-light endoscopy (WLE) alone. We aimed to assess the real-time diagnostic validity of high resolution endoscopy with and without NBI in the diagnosis of gastric premalignant conditions and to derive a classification for endoscopic grading of gastric intestinal metaplasia (EGGIM). METHODS: A multicenter prospective study (five centers: Portugal, Italy, Romania, UK, USA) was performed involving the systematic use of high resolution gastroscopes with image registry with and without NBI in a centralized informatics platform (available online). All users used the same NBI classification. Histologic result was considered the diagnostic gold standard. RESULTS: A total of 238 patients and 1123 endoscopic biopsies were included. NBI globally increased diagnostic accuracy by 11 percentage points (NBI 94 % vs. WLE 83 %; P < 0.001) with no difference in the identification of Helicobacter pylori gastritis (73 % vs. 74 %). NBI increased sensitivity for the diagnosis of intestinal metaplasia significantly (87 % vs. 53 %; P < 0.001) and for the diagnosis of dysplasia (92 % vs. 74 %). The added benefit of NBI in terms of diagnostic accuracy was greater in OLGIM III/IV than in OLGIM I/II (25 percentage points vs. 15 percentage points, respectively; P < 0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for EGGIM in the identification of extensive metaplasia was 0.98. CONCLUSIONS: In a real-time scenario, NBI demonstrates a high concordance with gastric histology, superior to WLE. Diagnostic accuracy higher than 90 % suggests that routine use of NBI allows targeted instead of random biopsy samples. EGGIM also permits immediate grading of intestinal metaplasia without biopsies and merits further investigation. PMID- 27280385 TI - Asynchronous learning: student utilization out of sync with their preference. AB - BACKGROUND: Asynchronous learning is gaining popularity. Data are limited regarding this learning method in medical students rotating in emergency medicine (EM). In EM, faculty time is limited to give in-person lectures. The authors sought to create an online curriculum that students could utilize as an additional learning modality. OBJECTIVE: The goal was to evaluate effectiveness, participation, and preference for this mode of learning. METHODS: We developed five online, narrated PowerPoint presentations. After orientation, access to the online curriculum was provided to the students, which they could review at their leisure. RESULTS: One hundred and seven fourth-year medical students participated. They reported the curriculum to be of high quality. Pretest scores were similar for those that viewed all lectures - compliant group (CG) (9.5 [CI 4.8-14.1]) and those that did not view any - non-compliant group (NCG) (9.6 [CI 5.9-13.4]). There was no statistical significant difference in posttest scores between the groups although there was improvement overall: CG 14.6 (CI 6.9-22.1); NCG 11.4 (CI 5.7-17.1). A majority (69.2%) favored inclusion of asynchronous learning, but less than a quarter (22.4%) reported viewing all five modules and more than a third (36.4%) viewed none. CONCLUSION: Despite student-expressed preference for an online curriculum, they used the online resource less than expected. This should give pause to educators looking to convert core EM topics to an online format. However, when high-quality online lectures are utilized as a learning tool, this study demonstrates that they had neither a positive nor a negative impact on test scores. PMID- 27280386 TI - Yeast Vps13 promotes mitochondrial function and is localized at membrane contact sites. AB - The Vps13 protein family is highly conserved in eukaryotic cells. Mutations in human VPS13 genes result in a variety of diseases, such as chorea acanthocytosis (ChAc), but the cellular functions of Vps13 proteins are not well defined. In yeast, there is a single VPS13 orthologue, which is required for at least two different processes: protein sorting to the vacuole and sporulation. This study demonstrates that VPS13 is also important for mitochondrial integrity. In addition to preventing transfer of DNA from the mitochondrion to the nucleus, VPS13 suppresses mitophagy and functions in parallel with the endoplasmic reticulum-mitochondrion encounter structure (ERMES). In different growth conditions, Vps13 localizes to endosome-mitochondrion contacts and to the nuclear vacuole junctions, indicating that Vps13 may function at membrane contact sites. The ability of VPS13 to compensate for the absence of ERMES correlates with its intracellular distribution. We propose that Vps13 is present at multiple membrane contact sites and that separation-of-function mutants are due to loss of Vps13 at specific junctions. Introduction of VPS13A mutations identified in ChAc patients at cognate sites in yeast VPS13 are specifically defective in compensating for the lack of ERMES, suggesting that mitochondrial dysfunction might be the basis for ChAc. PMID- 27280387 TI - Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage. AB - A functional DNA damage response is essential for maintaining genome integrity in the presence of DNA double-strand breaks. It is mainly coordinated by the kinases ATM, ATR, and DNA-PKcs, which control the repair of broken DNA strands and relay the damage signal to the tumor suppressor p53 to induce cell cycle arrest, apoptosis, or senescence. Although many functions of the individual kinases have been identified, it remains unclear how they act in concert to ensure faithful processing of the damage signal. Using specific inhibitors and quantitative analysis at the single-cell level, we systematically characterize the contribution of each kinase for regulating p53 activity. Our results reveal a new regulatory interplay in which loss of DNA-PKcs function leads to hyperactivation of ATM and amplification of the p53 response, sensitizing cells for damage induced senescence. This interplay determines the outcome of treatment regimens combining irradiation with DNA-PKcs inhibitors in a p53-dependent manner. PMID- 27280389 TI - Is preemptive antifungal therapy a good alternative to empirical treatment in prolonged febrile neutropenia? AB - Patients with prolonged febrile neutropenia are at high risk of invasive fungal infection, so it has been standard practice to initiate empirical antifungal therapy in these cases. However, this strategy is associated with important toxicity, so diagnostic test-guided preemptive antifungal therapy has been proposed as an alternative. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified three systematic reviews including twelve studies overall. Four randomized controlled trials addressed the question of this article. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded it is not clear whether preemptive strategy affects mortality because the certainty of the evidence is very low, but it might slightly decrease the use of antifungal agents in patients with prolonged febrile neutropenia. PMID- 27280388 TI - Phosphorylation of the RNA-binding protein Dazl by MAPKAP kinase 2 regulates spermatogenesis. AB - Developing male germ cells are exquisitely sensitive to environmental insults such as heat and oxidative stress. An additional characteristic of these cells is their unique dependence on RNA-binding proteins for regulating posttranscriptional gene expression and translational control. Here we provide a mechanistic link unifying these two features. We show that the germ cell-specific RNA-binding protein deleted in azoospermia-like (Dazl) is phosphorylated by MAPKAP kinase 2 (MK2), a stress-induced protein kinase activated downstream of p38 MAPK. We demonstrate that phosphorylation of Dazl by MK2 on an evolutionarily conserved serine residue inhibits its interaction with poly(A)-binding protein, resulting in reduced translation of Dazl-regulated target RNAs. We further show that transgenic expression of wild-type human Dazl but not a phosphomimetic form in the Drosophila male germline can restore fertility to flies deficient in boule, the Drosophila orthologue of human Dazl. These results illuminate a novel role for MK2 in spermatogenesis, expand the repertoire of RNA-binding proteins phosphorylated by this kinase, and suggest that signaling by the p38-MK2 pathway is a negative regulator of spermatogenesis via phosphorylation of Dazl. PMID- 27280390 TI - The Interaction Between Gender and Diabetes Mellitus in the Coronary Heart Disease Risk. AB - BACKGROUND: Cardiovascular disease (CVD) despite the advances in medical management keeps on as the primary cause of morbidity and mortality for both genders in Western societies. Sex differences though modify the clinical picture as well as the effectiveness of treatment. METHODS AND RESULTS: In this literature review article we searched publications in Englishlanguage on MEDLINE and the Cochrane Database from the beginning of the databases to January 2016. Among the specific key words and phrases we used were Diabetes Mellitus; Gender; Coronary artery disease; Stroke and Cardiovascular disease. Various studies have found that diabetic women have increased risk of coronary heart disease than their male counterparts; however, further research into this field has questioned this finding and there is much controversy among many researchers. Women have a different risk factor profile, are usually treated less effectively than men, and have a variance in the levels of sex hormones throughout their life which complicate the study and understanding of the mechanisms involved in insulin resistance, diabetes mellitus and cardiovascular risk profile. CONCLUSION: The connection between diabetes mellitus and cardiovascular disease is variable according to gender and further studies are needed to elucidate the lenient differentiations in gender specific hormones, risk factor profile, and therapeutic implications between genders. PMID- 27280391 TI - Identification and Characterization of Follistatin-Related Protein-1 Involved in the Regulation of Chinese Perch Skeletal Muscle Hyperplasia. AB - Follistatin-related protein (FSRP), which belongs to a member of the follistatin family, has been postulated to be a new negative regulator of myostatin (MSTN) and is involved in muscle development. In this study, we cloned the complete cDNA sequence of FSRP-1 from Chinese perch muscle. FSRP-1 mRNA was highly expressed in the fast muscle and brain tissue of adult fish. The expression of FSRP-1 rapidly increased at 90 days post hatching (dph) in the fast muscle of Chinese perch. Furthermore, to investigate the roles of FSRP-1 in muscle growth, we constructed a FSRP- 1 expression vector and isolated FSRP-1 fusion protein. The purified FSRP 1 fusion protein was injected into the muscle tissues of the Chinese perch (90 dph). The results showed that the number of muscle fibers and the satellite cell activation frequency were increased in the FSRP-1 treatment group. In addition, the myostatin (MSTN) expression was significantly decreased upon the FSRP-1 treatment. Collectively, the results suggest a possible mechanism of the FSRP-1 for inhibiting MSTN activity and enhancing muscle growth and renewal in vivo, and it may provide an applicable implication for the defected muscle repairing and regeneration. PMID- 27280392 TI - Nose to Brain Delivery of Nanoformulations for Neurotherapeutics in Parkinson's disease: Defining the Preclinical, Clinical and toxicity issues. AB - BACKGROUND: Parkinson's disease (PD) is depicted as the most prevailed neurodegenerative disease being secondary to the alzheimer's disease. PD is featured by severe dropping of dopamine related neurons present in substantia nigra as well as cytoplasmic inclusions. A number of therapeutic agents are available to treat initial as well as later complications of PD. However, transport of neurotherapeutics into the brain has been a consistent challenge for researchers, because of the existence of blood-brain barrier (BBB). In some last decades, nasal delivery pathway has gained extensive deliberations. Intranasal administration as a way to target neurotherapeutics to the central nervous system bypassing blood brain barrier, exhibit several advantages for treating neurodegenerative disorders. This route for transport of neurotherapeutics offers the merits of convenience of administration, avoidance of pre-systemic hepatic metabolism, and non- invasiveness. OBJECTIVE: The present review explores the novel nano sized formulations of various actives researched for intranasal drug transport to be used in PD therapy. Feasibility of various nano-carriers systems such as nano-emulsions, lipid nanoparticles and polymeric micelles has been elaborated. The write up traces the pre-clinical and pharmacokinetic aspects of the nano-formulations. The neuroprotection and neurotoxicity aspects have also been furnished. CONCLUSION: Nano-formulations are the rising formulations in PD treatment as they offer targeted drug delivery, enhanced therapeutic efficacy and decreased systemic side effects of neurotherapeutics. These formulations provide effective intranasal transport by encapsulating drug, protecting it from biological/chemical degradation and extracellular transport through P glycoprotein (P-gp) efflux thus, and enhancing CNS availability for drugs. PMID- 27280394 TI - PHGDH Expression Is Required for Mitochondrial Redox Homeostasis, Breast Cancer Stem Cell Maintenance, and Lung Metastasis. AB - Intratumoral hypoxia stimulates enrichment of breast cancer stem cells (BCSC), which are critical for metastasis and patient mortality. Here we report a metabolic adaptation that is required for hypoxia-induced BCSC enrichment and metastasis. Hypoxia-inducible factors coordinately regulate expression of genes encoding phosphoglycerate dehydrogenase (PHGDH) and five downstream enzymes in the serine synthesis pathway and mitochondrial one-carbon (folate) cycle. RNAi mediated silencing of PHGDH expression in both estrogen receptor-positive and negative breast cancer cells led to decreased NADPH levels, disturbed mitochondrial redox homeostasis, and increased apoptosis, which abrogated BCSC enrichment under hypoxic conditions. PHGDH-deficient cells exhibited increased oxidant levels and apoptosis, as well as loss of BCSC enrichment, in response to treatment with carboplatin or doxorubicin. PHGDH-deficient cells were relatively weakly tumorigenic and tumors that did form were deficient in BCSCs, abolishing metastatic capacity. Our findings highlight a role for PHGDH in the formation of secondary (recurrent or metastatic) tumors, with potential implications for therapeutic targeting of advanced cancers. Cancer Res; 76(15); 4430-42. (c)2016 AACR. PMID- 27280393 TI - Reduced Expression of Histone Methyltransferases KMT2C and KMT2D Correlates with Improved Outcome in Pancreatic Ductal Adenocarcinoma. AB - Genes encoding the histone H3 lysine 4 methyltransferases KMT2C and KMT2D are subject to deletion and mutation in pancreatic ductal adenocarcinoma (PDAC), where these lesions identify a group of patients with a more favorable prognosis. In this study, we demonstrate that low KMT2C and KMT2D expression in biopsies also defines better outcome groups, with median survivals of 15.9 versus 9.2 months (P = 0.029) and 19.9 versus 11.8 months (P = 0.001), respectively. Experiments with eight human pancreatic cell lines showed attenuated cell proliferation when these methyltransferases were depleted, suggesting that this improved outcome may reflect a cell-cycle block with diminished progression from G0-G1 RNA-seq analysis of PDAC cell lines following KMT2C or KMT2D knockdown identified 31 and 124 differentially expressed genes, respectively, with 19 genes in common. Gene-set enrichment analysis revealed significant downregulation of genes related to cell-cycle and growth. These data were corroborated independently by examining KMT2C/D signatures extracted from the International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Furthermore, these experiments highlighted a potential role for NCAPD3, a condensin II complex subunit, as an outcome predictor in PDAC using existing gene expression series. Kmt2d depletion in KC/KPC cell lines also led to an increased response to the nucleoside analogue 5-fluorouracil, suggesting that lower levels of this methyltransferase may mediate the sensitivity of PDAC to particular treatments. Therefore, it may also be therapeutically beneficial to target these methyltransferases in PDAC, especially in those patients demonstrating higher KTM2C/D expression. Cancer Res; 76(16); 4861-71. (c)2016 AACR. PMID- 27280395 TI - Nucleolin Promotes Heat Shock-Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis. AB - The vascular endothelial growth factor VEGF-D promotes metastasis by inducing lymphangiogenesis and dilatation of the lymphatic vasculature, facilitating tumor cell extravasion. Here we report a novel level of control for VEGF-D expression at the level of protein translation. In human tumor cells, VEGF-D colocalized with eIF4GI and 4E-BP1, which can program increased initiation at IRES motifs on mRNA by the translational initiation complex. In murine tumors, the steady-state level of VEGF-D protein was increased despite the overexpression and dephosphorylation of 4E-BP1, which downregulates protein synthesis, suggesting the presence of an internal ribosome entry site (IRES) in the 5' UTR of VEGF-D mRNA. We found that nucleolin, a nucleolar protein involved in ribosomal maturation, bound directly to the 5'UTR of VEGF-D mRNA, thereby improving its translation following heat shock stress via IRES activation. Nucleolin blockade by RNAi-mediated silencing or pharmacologic inhibition reduced VEGF-D translation along with a subsequent constriction of lymphatic vessels in tumors. Our results identify nucleolin as a key regulator of VEGF-D expression, deepening understanding of lymphangiogenesis control during tumor formation. Cancer Res; 76(15); 4394-405. (c)2016 AACR. PMID- 27280396 TI - Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted miR-150 Nanoparticles. AB - Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancy. Overexpression and/or mutations of FLT3 have been shown to occur in the majority of cases of AML. Our analysis of a large-scale AML patient cohort (N = 562) indicates that FLT3 is particularly highly expressed in some subtypes of AML, such as AML with t(11q23)/MLL-rearrangements or FLT3-ITD. Such AML subtypes are known to be associated with unfavorable prognosis. To treat FLT3 overexpressing AML, we developed a novel targeted nanoparticle system: FLT3 ligand (FLT3L)-conjugated G7 poly(amidoamine) (PAMAM) nanosized dendriplex encapsulating miR-150, a pivotal tumor suppressor and negative regulator of FLT3 We show that the FLT3L-guided miR-150 nanoparticles selectively and efficiently target FLT3-overexpressing AML cells and significantly inhibit viability/growth and promote apoptosis of the AML cells. Our proof-of-concept animal model studies demonstrate that the FLT3L-guided miR-150 nanoparticles tend to concentrate in bone marrow, and significantly inhibit progression of FLT3-overexpressing AML in vivo, while exhibiting no obvious side effects on normal hematopoiesis. Collectively, we have developed a novel targeted therapeutic strategy, using FLT3L-guided miR-150-based nanoparticles, to treat FLT3-overexpressing AML with high efficacy and minimal side effects. Cancer Res; 76(15); 4470-80. (c)2016 AACR. PMID- 27280398 TI - Evaluation of the Effects of Pasireotide LAR Administration on Lymphocele Prevention after Axillary Node Dissection for Breast Cancer: Results of a Randomized Non-Comparative Phase 2 Study. AB - OBJECTIVE: The aim of this study was to assess the efficacy (response rate centered on 80%) of a somatostatin analog with high affinity for 4 somatostatin receptors in reducing the postoperative incidence of symptomatic lymphocele formation following total mastectomy with axillary lymph node dissection. SETTING: This prospective, double-blind, randomised, placebo-controlled, phase 2 trial was conducted in two secondary care centres. PARTICIPANTS: All female patients for whom mastectomy and axillary lymph node dissection were indicated were eligible for the study, including patients who had received neo-adjuvant chemotherapy. Main exclusion criteria were related to diabetes, cardiac insufficiency, disorder of cardiac conduction or hepatic failure. INTERVENTIONS: Patients were randomised to receive one injection of either prolonged-release pasireotide 60 mg or placebo (physiological serum), which were administered intramuscularly 7 to 10 days before the scheduled surgery. The study was conducted in a double-blind manner. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the percentage of patients who did not develop post operative axillary symptomatic lymphoceles during the 2 postoperative months. Secondary endpoints were the total quantity of lymph drained, duration and daily volume of drainage and aspirated volumes of lymph. RESULTS: Ninety-one patients were randomised. Ninety patients were evaluable: 42 patients received pasireotide, and 48 patients received placebo. The mean estimated response rate were 62.4% (95% Credibility Interval [CrI]: 48.6%-75.3%) in the treatment group and 50.2% (95% CrI: 37.6%-62.8%) in the placebo group. Overall safety was comparable across groups, and one serious adverse event occurred. In the treatment group, one patient with known insulin-depe*ndent diabetes required hospitalization for hyperglycaemia. CONCLUSIONS: With this phase 2 preliminary study, even if our results indicate a trend towards a reduction in symptomatic lymphocele, pre-operative injection of pasireotide failed to achieve a response rate centered on 80%. Pharmacokinetics analysis suggests that effect of pasireotide could be optimised. TRIAL REGISTRATION: ClinicalTrials.gov NCT01356862. PMID- 27280400 TI - Correction: Decoding Sensorimotor Rhythms during Robotic-Assisted Treadmill Walking for Brain Computer Interface (BCI) Applications. AB - [This corrects the article DOI: 10.1371/journal.pone.0137910.]. PMID- 27280399 TI - Dectin-3 Deficiency Promotes Colitis Development due to Impaired Antifungal Innate Immune Responses in the Gut. AB - Interactions between commensal fungi and gut immune system are critical for establishing colonic homeostasis. Here we found that mice deficient in Dectin-3 (Clec4d-/-), a C-type lectin receptor that senses fungal infection, were more susceptible to dextran sodium sulfate (DSS)-induced colitis compared with wild type mice. The specific fungal burden of Candida (C.) tropicalis was markedly increased in the gut after DSS treatment in Clec4d-/- mice, and supplementation with C. tropicalis aggravated colitis only in Clec4d-/- mice, but not in wild type controls. Mechanistically, Dectin-3 deficiency impairs phagocytic and fungicidal abilities of macrophages, and C. tropicalis-induced NF-kappaB activation and cytokine production. The conditioned media derived from Dectin-3 deficient macrophages were defective in promoting tissue repairing in colonic epithelial cells. Finally, anti-fungal therapy was effective in treating colitis in Clec4d-/- mice. These studies identified the role of Dectin-3 and its functional interaction with commensal fungi in intestinal immune system and regulation of colonic homeostasis. PMID- 27280401 TI - Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration. AB - For efficient polarity and migration, cells need to regulate the magnitude and spatial distribution of actin assembly. This process is coordinated by reciprocal interactions between the actin cytoskeleton and mechanical forces. Actin polymerization-based protrusion increases tension in the plasma membrane, which in turn acts as a long-range inhibitor of actin assembly. These interactions form a negative feedback circuit that limits the magnitude of membrane tension in neutrophils and prevents expansion of the existing front and the formation of secondary fronts. It has been suggested that the plasma membrane directly inhibits actin assembly by serving as a physical barrier that opposes protrusion. Here we show that efficient control of actin polymerization-based protrusion requires an additional mechanosensory feedback cascade that indirectly links membrane tension with actin assembly. Specifically, elevated membrane tension acts through phospholipase D2 (PLD2) and the mammalian target of rapamycin complex 2 (mTORC2) to limit actin nucleation. In the absence of this pathway, neutrophils exhibit larger leading edges, higher membrane tension, and profoundly defective chemotaxis. Mathematical modeling suggests roles for both the direct (mechanical) and indirect (biochemical via PLD2 and mTORC2) feedback loops in organizing cell polarity and motility-the indirect loop is better suited to enable competition between fronts, whereas the direct loop helps spatially organize actin nucleation for efficient leading edge formation and cell movement. This circuit is essential for polarity, motility, and the control of membrane tension. PMID- 27280402 TI - FLCN Maintains the Leucine Level in Lysosome to Stimulate mTORC1. AB - The intracellular amino acid pool within lysosome is a signal that stimulates the nutrient-sensing mTORC1 signalling pathway. The signal transduction cascade has garnered much attention, but little is known about the sequestration of the signalling molecules within the lysosome. Using human HEK293 cells as a model, we found that suppression of the BHD syndrome gene FLCN reduced the leucine level in lysosome, which correlated with decreased mTORC1 activity. Both consequences could be reversed by supplementation with high levels of leucine, but not other tested amino acids. Conversely, overexpressed FLCN could sequester lysosomal leucine and stimulate mTORC1 in an amino acid limitation environment. These results identify a novel function of FLCN: it controls mTORC1 by modulating the leucine signal in lysosome. Furthermore, we provided evidence that FLCN exerted this role by inhibiting the accumulation of the amino acid transporter PAT1 on the lysosome surface, thereby maintaining the signal level within the organelle. PMID- 27280403 TI - Exposure of Human CD4 T Cells to IL-12 Results in Enhanced TCR-Induced Cytokine Production, Altered TCR Signaling, and Increased Oxidative Metabolism. AB - Human CD4 T cells are constantly exposed to IL-12 during infections and certain autoimmune disorders. The current paradigm is that IL-12 promotes the differentiation of naive CD4 T cells into Th1 cells, but recent studies suggest IL-12 may play a more complex role in T cell biology. We examined if exposure to IL-12 alters human CD4 T cell responses to subsequent TCR stimulation. We found that IL-12 pretreatment increased TCR-induced IFN-gamma, TNF-alpha, IL-13, IL-4 and IL-10 production. This suggests that prior exposure to IL-12 potentiates the TCR-induced release of a range of cytokines. We observed that IL-12 mediated its effects through both transcriptional and post-transcriptional mechanisms. IL-12 pretreatment increased the phosphorylation of AKT, p38 and LCK following TCR stimulation without altering other TCR signaling molecules, potentially mediating the increase in transcription of cytokines. In addition, the IL-12-mediated enhancement of cytokines that are not transcriptionally regulated was partially driven by increased oxidative metabolism. Our data uncover a novel function of IL 12 in human CD4 T cells; specifically, it enhances the release of a range of cytokines potentially by altering TCR signaling pathways and by enhancing oxidative metabolism. PMID- 27280404 TI - Retention of HIV-Infected Children in the First 12 Months of Anti-Retroviral Therapy and Predictors of Attrition in Resource Limited Settings: A Systematic Review. AB - Current UNAIDS goals aimed to end the AIDS epidemic set out to ensure that 90% of all people living with HIV know their status, 90% initiate and continue life-long anti-retroviral therapy (ART), and 90% achieve viral load suppression. In 2014 there were an estimated 2.6 million children under 15 years of age living with HIV, of which only one-third were receiving ART. Little literature exists describing retention of HIV-infected children in the first year on ART. We conducted a systematic search for English language publications reporting on retention of children with median age at ART initiation less than ten years in resource limited settings. The proportion of children retained in care on ART and predictors of attrition were identified. Twelve studies documented retention at one year ranging from 71-95% amongst 31877 African children. Among the 5558 children not retained, 4082 (73%) were reported as lost to follow up (LFU) and 1476 (27%) were confirmed to have died. No studies confirmed the outcomes of children LFU. Predictors of attrition included younger age, shorter duration of time on ART, and severe immunosuppression. In conclusion, significant attrition occurs in children in the first 12 months after ART initiation, the majority attributed to LFU, although true outcomes of children labeled as LFU are unknown. Focused efforts to ensure retention and minimize early mortality are needed as universal ART for children is scaled up. PMID- 27280405 TI - Identification of Multiple Loci Associated with Social Parasitism in Honeybees. AB - In colonies of the honeybee Apis mellifera, the queen is usually the only reproductive female, which produces new females (queens and workers) by laying fertilized eggs. However, in one subspecies of A. mellifera, known as the Cape bee (A. m. capensis), worker bees reproduce asexually by thelytoky, an abnormal form of meiosis where two daughter nucleii fuse to form single diploid eggs, which develop into females without being fertilized. The Cape bee also exhibits a suite of phenotypes that facilitate social parasitism whereby workers lay such eggs in foreign colonies so their offspring can exploit their resources. The genetic basis of this switch to social parasitism in the Cape bee is unknown. To address this, we compared genome variation in a sample of Cape bees with other African populations. We find genetic divergence between these populations to be very low on average but identify several regions of the genome with extreme differentiation. The regions are strongly enriched for signals of selection in Cape bees, indicating that increased levels of positive selection have produced the unique set of derived phenotypic traits in this subspecies. Genetic variation within these regions allows unambiguous genetic identification of Cape bees and likely underlies the genetic basis of social parasitism. The candidate loci include genes involved in ecdysteroid signaling and juvenile hormone and dopamine biosynthesis, which may regulate worker ovary activation and others whose products localize at the centrosome and are implicated in chromosomal segregation during meiosis. Functional analysis of these loci will yield insights into the processes of reproduction and chemical signaling in both parasitic and non parasitic populations and advance understanding of the process of normal and atypical meiosis. PMID- 27280406 TI - Histidine Prevents Cu-Induced Oxidative Stress and the Associated Decreases in mRNA from Encoding Tight Junction Proteins in the Intestine of Grass Carp (Ctenopharyngodon idella). AB - Copper (Cu) is a common heavy metal pollutant in aquatic environments that originates from natural as well as anthropogenic sources. The present study investigated whether Cu causes oxidative damage and induces changes in the expression of genes that encode tight junction (TJ) proteins, cytokines and antioxidant-related genes in the intestine of the grass carp (Ctenopharyngodon idella). We demonstrated that Cu decreases the survival rate of fish and increases oxidative damage as measured by increases in malondialdehyde and protein carbonyl contents. Cu exposure significantly decreased the expression of genes that encode the tight junction proteins, namely, claudin (CLDN)-c, -3 and 15 as well as occludin and zonula occludens-1, in the intestine of fish. In addition, Cu exposure increases the mRNA levels of the pro-inflammatory cytokines, specifically, IL-8, TNF-alpha and its related signalling factor (nuclear factor kappa B, NF-kappaB), which was partly correlated to the decreased mRNA levels of NF-kappaB inhibitor protein (IkappaB). These changes were associated with Cu-induced oxidative stress detected by corresponding decreases in glutathione (GSH) content, as well as decreases in the copper, zinc-superoxide dismutase (SOD1) and glutathione peroxidase (GPx) activities and mRNA levels, which were associated with the down-regulated antioxidant signalling factor NF-E2 related factor-2 (Nrf2) mRNA levels, and the Kelch-like-ECH-associated protein1 (Keap1) mRNA levels in the intestine of fish. Histidine supplementation in diets (3.7 up to 12.2 g/kg) blocked Cu-induced changes. These results indicated that Cu induced decreases in intestinal TJ proteins and cytokine mRNA levels might be partially mediated by oxidative stress and are prevented by histidine supplementation in fish diet. PMID- 27280407 TI - Diagnostic Performance of Indocyanine Green-Guided Sentinel Lymph Node Biopsy in Breast Cancer: A Meta-Analysis. AB - BACKGROUND: The diagnostic performance of indocyanine green (ICG) fluorescence guided sentinel lymph node biopsy (SLNB) for the presence of metastases in breast cancer remains unclear. OBJECTIVE: We performed a meta-analysis to investigate the diagnostic performance of ICG-guided SLNB. METHODS: Eligible studies were identified from searches of the databases PubMed and EMBASE up to September 2015. Studies that reported the detection rate of ICG fluorescence-guided SLNB with full axillary lymph node dissection and histological or immunohistochemical examinations were included. A meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, false negative rate, diagnostic odds ratio (DOR) and a summary receiver operator characteristic curve (SROC). RESULTS: Nineteen published studies were included to generate a pooled detection rate, comprising 2594 patients. The pooled detection rate was 0.98 (95% confidence interval [CI], 0.96-0.99). Six studies finally met the criteria for meta analysis, which yielded a pooled sensitivity of 0.92 (95% CI, 0.85-0.96), specificity 1 (95% CI, 0.97-1), and DOR 311.47 (95% CI, 84.11-1153.39). The area under the SROC was 0.9758. No publication bias was found. CONCLUSION: ICG fluorescence-guided SLNB is viable for detection of lymph node metastases in breast cancer. Large-scale randomized multi-center trials are necessary to confirm our results. PMID- 27280408 TI - Secondary Education and Health Outcomes in Young People from the Cape Area Panel Study (CAPS). AB - AIM: Education is one of the strongest social determinants of health, yet previous literature has focused on primary education. We examined whether there are additional benefits to completing upper secondary compared to lower secondary education in a middle-income country. METHODS: We performed a longitudinal analysis of the Cape Area Panel Study, a survey of adolescents living in South Africa. We undertook causal modeling using structural marginal models to examine the association between level of education and various health outcomes, using inverse probability weighting to control for sex, age, ethnicity, home language, income, whether employed in past year, region of birth, maternal educational status, marital status, whether currently pregnant and cognitive ability. Educational attainment was defined as primary (grades 1-7), lower secondary (grades 8-9) or upper secondary (grades 10-12). RESULTS: Of 3,432 participants, 165 (4.8%) had completed primary education, 646 (18.8%) lower secondary and 2,621 (76.3%) upper secondary. Compared to those completing lower secondary, males completing upper secondary education were less likely to have a health problem (OR 0.49; 95%CI 0.27-0.88; p = 0.02); describe their health as poor (0.52; 0.29 0.95; p = 0.03) or report that health interferes with daily life (0.54; 0.29 0.99; p = 0.047). Females were less likely to have been pregnant (0.45; 0.33 0.61; p<0.001) or pregnant under 18 (0.32; 0.22-0.46; p<0.001); and having had sex under 16 was also less likely (males 0.63; 0.44-0.91; p = 0.01; females 0.39; 0.26-0.58; p<0.001). Cigarette smoking was less likely (males 0.52; 0.38-0.70; p = <0.001; females 0.56; 0.41-0.76; p<0.001), as was taking illicit drugs in males (0.6; 0.38-0.96; p = 0.03). No associations were found between education and alcohol use, psychological distress, obesity, increased waist circumference or hypertension. CONCLUSION: Completing upper secondary education was associated with improved health outcomes compared with lower secondary education. Expanding upper secondary education offers middle-income countries an effective way of improving adolescent health. PMID- 27280409 TI - Convergent evolution of pregnancy-specific glycoproteins in human and horse. AB - Pregnancy-specific glycoproteins (PSGs) are members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family that are secreted by trophoblast cells. PSGs may modulate immune, angiogenic and platelet responses during pregnancy. Until now, PSGs are only found in species that have a highly invasive (hemochorial) placentation including humans, mice and rats. Surprisingly, analyzing the CEACAM gene family of the horse, which has a non-invasive epitheliochorial placenta, with the exception of the transient endometrial cups, we identified equine CEACAM family members that seem to be related to PSGs of rodents and primates. We identified seven genes that encode secreted PSG-like CEACAMs Phylogenetic analyses indicate that they evolved independently from an equine CEACAM1-like ancestor rather than from a common PSG-like ancestor with rodents and primates. Significantly, expression of PSG-like genes (CEACAM44, CEACAM48, CEACAM49 and CEACAM55) was found in non-invasive as well as invasive trophoblast cells such as purified chorionic girdle cells and endometrial cup cells. Chorionic girdle cells are highly invasive trophoblast cells that invade the endometrium of the mare where they form endometrial cups and are in close contact with maternal immune cells. Therefore, the microenvironment of invasive equine trophoblast cells has striking similarities to the microenvironment of trophoblast cells in hemochorial placentas, suggesting that equine PSG-like CEACAMs and rodent and primate PSGs have undergone convergent evolution. This is supported by our finding that equine PSG-like CEACAM49 exhibits similar activity to certain rodent and human PSGs in a functional assay of platelet-fibrinogen binding. Our results have implications for understanding the evolution of PSGs and their functions in maternal-fetal interactions. PMID- 27280410 TI - Different Growth Responses of an Invasive Weed and a Native Crop to Nitrogen Pulse and Competition. AB - Resource pulses are a common event in agro-ecosystems. A pot experiment was conducted to assess the effects of nitrogen (N) pulses and competition on the growth of an invasive weed, Amaranthus retroflexus, and a native crop, Glycine max. A. retroflexus and G. max were planted in pure culture with two individuals of one species in each pot and in mixed culture with one A. retroflexus and one G. max individual and subjected to three N pulse treatments. The N treatments included a no-peak treatment (NP) with N applied stably across the growing period, a single-peak treatment (SP) with only one N addition on the planting date, and a double-peak treatment (DP) with two N additions, one on the planting date and the other on the flowering date. N pulse significantly impacted biomass and height of the two species across the whole growing season. However, only the relative growth rate (RGR) of A. retroflexus was significantly affected by N pulse. A. retroflexus had the greatest biomass and height in the SP treatment at the first harvest, and in the DP treatment at the last three harvests. Pure culture G. max produced the greatest biomass in the DP treatment. In mixed culture, G. max produced the greatest biomass in the NP treatment. Biomass production of both species was significantly influenced by species combination, with higher biomass in mixed culture than in pure culture at most growth stages. Relative yield total (RYT) values were all greater than 1.0 at the last three harvests across the three N treatments, suggesting partial resource complementarity occurred when A. retroflexus is grown with G. max. These results indicate that A. retroflexus has a strong adaptive capacity to reduce interspecific competition, likely leading to its invasion of G. max cropland in China. PMID- 27280411 TI - Lay and professional stakeholder involvement in scoping palliative care issues: Methods used in seven European countries. AB - BACKGROUND: Stakeholders are people with an interest in a topic. Internationally, stakeholder involvement in palliative care research and health technology assessment requires development. Stakeholder involvement adds value throughout research (from prioritising topics to disseminating findings). Philosophies and understandings about the best ways to involve stakeholders in research differ internationally. Stakeholder involvement took place in seven countries (England, Germany, Italy, Lithuania, the Netherlands, Norway and Poland). Findings informed a project that developed concepts and methods for health technology assessment and applied these to evaluate models of palliative care service delivery. AIMS: To report on stakeholder involvement in the INTEGRATE-HTA project and how issues identified informed project development. DESIGN: Using stakeholder consultation or a qualitative research design, as appropriate locally, stakeholders in seven countries acted as 'advisors' to aid researchers' decision making. Thematic analysis was used to identify key issues across countries. SETTING/PARTICIPANTS: A total of 132 stakeholders (82 professionals and 50 'lay' people) aged ?18 participated in individual face-to-face or telephone interviews, consultation meetings or focus groups. RESULTS: Different stakeholder involvement methods were used successfully to identify key issues in palliative care. A total of 23 issues common to three or more countries informed decisions about the intervention and comparator of interest, sub questions and specific assessments within the health technology assessment. CONCLUSION: Stakeholders, including patients and families undergoing palliative care, can inform project decision making using various involvement methods according to the local context. Researchers should consider local understandings about stakeholder involvement as views of appropriate and feasible methods vary. Methods for stakeholder involvement, especially consultation, need further development. PMID- 27280412 TI - Hyaluronic acid: Perspectives in dentistry. A systematic review. AB - To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the soft periodontal tissue, gingiva, and periodontal ligament as well as to the hard tissue such as alveolar bone and cementum. Topical hyaluronic acid (HA) has recently been recognized as an adjuvant treatment for chronic inflammatory disease in addition to its use to improve healing after dental procedures. The aim of our work was to systematically review the published literature about potential effects of HA as an adjuvant treatment for chronic inflammatory disease, in addition to its use to improve healing after common dental procedures. Relevant published studies were found in PubMed, Google Scholar, and Ovid using a combined keyword search or medical subject headings. At the end of our study selection process, 25 relevant publications were included, three of them regarding gingivitis, 13 of them relating to chronic periodontitis, seven of them relating to dental surgery, including implant and sinus lift procedures, and the remaining three articles describing oral ulcers. Not only does topical administration of HA play a pivotal key role in the postoperative care of patients undergoing dental procedures, but positive results were also generally observed in all patients with chronic inflammatory gingival and periodontal disease and in patients with oral ulcers. PMID- 27280413 TI - Expression of Molecular Differentiation Markers Does Not Correlate with Histological Differentiation Grade in Intrahepatic Cholangiocarcinoma. AB - The differentiation status of tumor cells, defined by histomorphological criteria, is a prognostic factor for survival of patients affected with intrahepatic cholangiocarcinoma (ICC). To strengthen the value of morphological differentiation criteria, we wished to correlate histopathological differentiation grade with expression of molecular biliary differentiation markers and of microRNAs previously shown to be dysregulated in ICC. We analysed a series of tumors that were histologically classified as well, moderately or poorly differentiated, and investigated the expression of cytokeratin 7, 19 and 903 (CK7, CK19, CK903), SRY-related HMG box transcription factors 4 and 9 (SOX4, SOX9), osteopontin (OPN), Hepatocyte Nuclear Factor-1 beta (HNF1beta), Yes associated protein (YAP), Epithelial cell adhesion molecule (EPCAM), Mucin 1 (MUC1) and N-cadherin (NCAD) by qRT-PCR and immunostaining, and of miR-31, miR 135b, miR-132, miR-200c, miR-221 and miR-222. Unexpectedly, except for subcellular location of SOX9 and OPN, no correlation was found between the expression levels of these molecular markers and histopathological differentiation grade. Therefore, our data point toward necessary caution when investigating the evolution and prognosis of ICC on the basis of cell differentiation criteria. PMID- 27280414 TI - Inherent Variability of Growth Media Impacts the Ability of Salmonella Typhimurium to Interact with Host Cells. AB - Efficient invasion of non-phagocytic cells, such as intestinal epithelial cells, by Salmonella Typhimurium is dependent on the Salmonella Pathogenicity Island 1 (SPI-1)-encoded Type Three Secretion System. The environmental cues involved in SPI-1 induction are not well understood. In vitro, various conditions are used to induce SPI-1 and the invasive phenotype. Although lysogeny broth (LB) is widely used, multiple formulations exist, and variation can arise due to intrinsic differences in complex components. Minimal media are also susceptible to variation. Still, the impact of these inconsistencies on Salmonella virulence gene expression has not been well studied. The goal of this project is to identify growth conditions in LB and minimal medium that affect SPI-1 induction in vitro using both whole population and single cell analysis. Here we show, using a fluorescent reporter of the SPI-1 gene prgH, that growth of Salmonella in LB yields variable induction. Deliberate modification of media components can influence the invasive profile. Finally, we demonstrate that changes in SPI-1 inducing conditions can affect the ability of Salmonella to replicate intracellularly. These data indicate that the specific media growth conditions impact how the bacteria interact with host cells. PMID- 27280415 TI - Sharing Responsibilities within the General Practice Team - A Cross-Sectional Study of Task Delegation in Germany. AB - BACKGROUND: Expected growth in the demand for health services has generated interest in the more effective deployment of health care assistants. Programs encouraging German general practitioners (GPs) to share responsibility for care with specially qualified health care assistants in the family practice (VERAHs) have existed for several years. But no studies have been conducted on the tasks German GPs are willing to rely on specially qualified personnel to perform, what they are prepared to delegate to all non-physician practice staff and what they prefer to do themselves. METHODS: As part of an evaluation study on the deployment of VERAHs in GP-centered health care, we used a questionnaire to ask about task delegation within the practice team. From a list of tasks that VERAHs are specifically trained to carry out, GPs were asked to indicate which they actually delegate. We also asked GPs why they had employed a VERAH in their practice and for their opinions on the benefits and limitations of assigning tasks to VERAHs. The aim of the study was to find out which tasks GPs delegate to their specially qualified personnel, which they permit all HCAs to carry out, and which tasks they do not delegate at all. RESULTS: The survey was filled in and returned by 245 GPs (83%). Some tasks were exclusively delegated to VERAHs (e.g. home visits), while others were delegated to all HCAs (e.g. vaccinations). About half the GPs rated the assessment of mental health, as part of the comprehensive assessment of a patient's condition, as the sole responsibility of a GP. The possibility to delegate more complex tasks was the main reason given for employing a VERAH. Doctors said the delegation of home visits provided them with the greatest relief. CONCLUSIONS: In Germany, where GPs are solely accountable for the health care provided in their practices, experience with the transfer of responsibility to other non-physician health care personnel is still very limited. When HCAs have undergone special training, GPs seem to be prepared to delegate tasks that demand a substantial degree of know-how, such as home visits and case management. This "new" role allocation within the practice may signal a shift in the provision of health care by family practice teams in Germany. PMID- 27280416 TI - Reproductive Seasonality in Nesticus (Araneae: Nesticidae) Cave Spiders. AB - Spiders of the family Nesticidae are members of cave communities around the world with cave-obligate (troglobiotic) species known from North America, Europe, Asia and the Indo-Pacific. A radiation of Nesticus (Araneae: Nesticidae) in the southern Appalachians includes ten troglobiotic species. Many of these species are of conservation interest due to their small ranges, with four species being single-cave endemics. Despite conservation concerns and their important role as predators in cave communities, we know little about reproduction and feeding in this group. We addressed this knowledge gap by examining populations of two species on a monthly basis for one year. We made further observations on several other species and populations, totaling 671 individual spider observations. This more than doubled the reported observations of reproduction and feeding in troglobiotic Nesticus. Female Nesticus carry egg sacs, facilitating the determination of the timing and frequency of reproduction. We found that Nesticus exhibit reproductive seasonality. Females carried egg sacs from May through October, with a peak in frequency in June. These spiders were rarely observed with prey; only 3.3% (22/671) of individuals were observed with prey items. The frequency at which prey items were observed did not vary by season. Common prey items were flies, beetles and millipedes. Troglobiotic species constituted approximately half of all prey items observed. This result represents a greater proportion of troglobiotic prey than has been reported for various troglophilic spiders. Although our findings shed light on the life history of troglobiotic Nesticus and on their role in cave ecosystems, further work is necessary to support effective conservation planning for many of these rare species. PMID- 27280417 TI - Biographical Feature: Patrick R. Murray, Ph.D. PMID- 27280418 TI - Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot Assay but Not CMV QuantiFERON Assay Is a Novel Biomarker To Determine Risk of Congenital CMV Infection in Pregnant Women. AB - Cytomegalovirus (CMV) enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays were examined as potential biomarkers predictive of congenital CMV (cCMV) transmission. Fifty-seven pregnant women with primary CMV infection and 23 with nonprimary CMV infection were recruited in the study. Maternal age, CMV IgG avidity, viremia, and viruria were also included among the potential predictors. Spearman's statistical correlation analysis revealed a positive correlation between the CMV ELISPOT and CMV QuantiFERON assay results (P < 0.001), but only the CMV ELISPOT assay correlated with cCMV (P < 0.001). cCMV was positively correlated with maternal viremia and viruria (P < 0.05) and negatively correlated with CMV IgG avidity (P < 0.01). Maternal age and CMV QuantiFERON assay results were not statistically associated with cCMV. CMV-specific cell mediated immunity detected by the CMV ELISPOT assay plays a critical role in cCMV. PMID- 27280419 TI - Performance of Etest for Antimicrobial Susceptibility Testing of Abiotrophia defectiva and Granulicatella Species. AB - The Etest on chocolate Mueller-Hinton agar was compared to broth microdilution (BMD) for 125 isolates of nutritionally variant streptococci. Vancomycin Etests yielded 31.1% essential agreement (EA) and 20.0% categorical agreement (CA). Penicillin Etests yielded 86.0% EA and 85.6% CA, whereas ceftriaxone Etests yielded 73.6% EA and 68.0% CA. PMID- 27280420 TI - Evaluation of an Optimal Epidemiological Typing Scheme for Legionella pneumophila with Whole-Genome Sequence Data Using Validation Guidelines. AB - Sequence-based typing (SBT), analogous to multilocus sequence typing (MLST), is the current "gold standard" typing method for investigation of legionellosis outbreaks caused by Legionella pneumophila However, as common sequence types (STs) cause many infections, some investigations remain unresolved. In this study, various whole-genome sequencing (WGS)-based methods were evaluated according to published guidelines, including (i) a single nucleotide polymorphism (SNP)-based method, (ii) extended MLST using different numbers of genes, (iii) determination of gene presence or absence, and (iv) a kmer-based method. L. pneumophila serogroup 1 isolates (n = 106) from the standard "typing panel," previously used by the European Society for Clinical Microbiology Study Group on Legionella Infections (ESGLI), were tested together with another 229 isolates. Over 98% of isolates were considered typeable using the SNP- and kmer-based methods. Percentages of isolates with complete extended MLST profiles ranged from 99.1% (50 genes) to 86.8% (1,455 genes), while only 41.5% produced a full profile with the gene presence/absence scheme. Replicates demonstrated that all methods offer 100% reproducibility. Indices of discrimination range from 0.972 (ribosomal MLST) to 0.999 (SNP based), and all values were higher than that achieved with SBT (0.940). Epidemiological concordance is generally inversely related to discriminatory power. We propose that an extended MLST scheme with ~50 genes provides optimal epidemiological concordance while substantially improving the discrimination offered by SBT and can be used as part of a hierarchical typing scheme that should maintain backwards compatibility and increase discrimination where necessary. This analysis will be useful for the ESGLI to design a scheme that has the potential to become the new gold standard typing method for L. pneumophila. PMID- 27280421 TI - Laboratory Diagnosis of Infections in Cancer Patients: Challenges and Opportunities. AB - Infections remain a significant cause of morbidity and mortality in cancer patients. The differential diagnosis for these patients is often wide, and the timely selection of the right clinical tests can have a significant impact on their survival. However, laboratory findings with current methodologies are often negative, challenging clinicians and laboratorians to continue the search for the responsible pathogen. Novel methodologies are providing increased sensitivity and rapid turnaround time to results but also challenging our interpretation of what is a clinically significant pathogen in cancer patients. This minireview provides an overview of the most common infections in cancer patients and discusses some of the challenges and opportunities for the clinical microbiologist supporting the care of cancer patients. PMID- 27280422 TI - Identification and Antifungal Susceptibility of Penicillium-Like Fungi from Clinical Samples in the United States. AB - Penicillium species are some of the most common fungi observed worldwide and have an important economic impact as well as being occasional agents of human and animal mycoses. A total of 118 isolates thought to belong to the genus Penicillium based on morphological features were obtained from the Fungus Testing Laboratory at the University of Texas Health Science Center in San Antonio (United States). The isolates were studied phenotypically using standard growth conditions. Molecular identification was made using two genetic markers, the internal transcribed spacer (ITS) and a fragment of the beta-tubulin gene. In order to assess phylogenetic relationships, maximum likelihood and Bayesian inference assessments were used. Antifungal susceptibility testing was performed according to CLSI document M38-A2 for nine antifungal drugs. The isolates were identified within three genera, i.e., Penicillium, Talaromyces, and Rasamsonia The most frequent species in our study were Penicillium rubens, P. citrinum, and Talaromyces amestolkiae The potent in vitro activity of amphotericin B (AMB) and terbinafine (TRB) and of the echinocandins against Penicillium and Talaromyces species might offer a good therapeutic alternative for the treatment of infections caused by these fungi. PMID- 27280423 TI - Single-Step Multiplex PCR Assay for Determining 92 Pneumococcal Serotypes. AB - For pneumococcal disease surveillance, simple and cost-effective methods capable of determining all serotypes are needed. Combining a single-tube multiplex PCR with fluorescently labeled primers followed by amplicon analysis using automated fluorescent capillary electrophoresis, each serotype of 92 reference isolates and 297 recently collected clinical isolates was successfully determined. PMID- 27280424 TI - QuickStats: Smoking Cessation* During Pregnancy - 46 States and the District of Columbia, 2014. AB - In 2014, 20.6% of pregnant women who smoked cigarettes during the first or second trimester, in a reporting area of 46 states and the District of Columbia, stopped smoking during pregnancy. Women in three states, South Dakota (31.3%), California (31.2%) and New Mexico (30.2%), as well as the District of Columbia (41.5%), reported the highest cessation rates during pregnancy. Kentucky (11.4%) and Maine (11.6%) reported the lowest cessation rates; cessation rates were generally lower for states in the Southeast. The reporting area included 3,819,113 births and represented 95% of all U.S. births in 2014. PMID- 27280425 TI - Man or machine? An experimental study of prehospital emergency amputation. AB - OBJECTIVE: Prehospital emergency amputation is a rare procedure, which may be necessary to free a time-critical patient from entrapment. This study aimed to evaluate four techniques of cadaveric lower limb prehospital emergency amputation. METHOD: A guillotine amputation of the distal femur was undertaken in fresh frozen self-donated cadavers. A prehospital doctor conducted a surgical amputation with Gigli saw or hacksaw for bone cuts and firefighters carried out the procedure using the reciprocating saw and Holmatro device. The primary outcome measures were time to full amputation and the number of attempts required. The secondary outcomes were observed quality of skin cut, soft tissue cut and CT assessment of the proximal bone. Observers also noted the potential risks to the rescuer or patient during the procedure. RESULTS: All techniques completed amputation within 91 s. The reciprocating saw was the quickest technique (22 s) but there was significant blood spattering and continuation of the cut to the surface under the leg. The Holmatro device took less than a minute. The quality of the proximal femur was acceptable with all methods, but 5 cm more proximal soft tissue damage was made by the Holmatro device. CONCLUSIONS: Emergency prehospital guillotine amputation of the distal femur can effectively be performed using scalpel and paramedic shears with bone cuts by the Gigli saw or fire service hacksaw. The reciprocating saw could be used to cut bone if no other equipment was available but carried some risks. The Holmatro cutting device is a viable option for a life-threatening entrapment where only firefighters can safely access the patient, but would not be a recommended primary technique for medical staff. PMID- 27280426 TI - High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ETB receptor expression. AB - The collecting duct endothelin-1 (ET-1), endothelin B (ETB) receptor, and nitric oxide synthase-1 (NOS1) pathways are critical for regulation of fluid-electrolyte balance and blood pressure control during high-salt feeding. ET-1, ETB receptor, and NOS1 are highly expressed in the inner medullary collecting duct (IMCD) and vasa recta, suggesting that there may be cross talk or paracrine signaling between the vasa recta and IMCD. The purpose of this study was to test the hypothesis that endothelial cell-derived ET-1 (paracrine) and collecting duct derived ET-1 (autocrine) promote IMCD nitric oxide (NO) production through activation of the ETB receptor during high-salt feeding. We determined that after 7 days of a high-salt diet (HS7), there was a shift to 100% ETB expression in IMCDs, as well as a twofold increase in nitrite production (a metabolite of NO), and this increase could be prevented by acute inhibition of the ETB receptor. ETB receptor blockade or NOS1 inhibition also prevented the ET-1-dependent decrease in ion transport from primary IMCDs, as determined by transepithelial resistance. IMCD were also isolated from vascular endothelial ET-1 knockout mice (VEETKO), collecting duct ET-1 KO (CDET-1KO), and flox controls. Nitrite production by IMCD from VEETKO and flox mice was similarly increased twofold with HS7. However, IMCD NO production from CDET-1KO mice was significantly blunted with HS7 compared with flox control. Taken together, these data indicate that during high-salt feeding, the autocrine actions of ET-1 via upregulation of the ETB receptor are critical for IMCD NO production, facilitating inhibition of ion reabsorption. PMID- 27280427 TI - Exaggerated sympathoexcitatory reflexes develop with changes in the rostral ventrolateral medulla in obese Zucker rats. AB - Obesity leads to altered autonomic reflexes that reduce stability of mean arterial pressure (MAP). Sympathoinhibitory reflexes such as baroreflexes are impaired, but reflexes that raise MAP appear to be augmented. In obese Zucker rats (OZR) sciatic nerve stimulation evokes larger increases in MAP by unknown mechanisms. We sought to determine the autonomic underpinnings of this enhanced somatic pressor reflex and whether other sympathoexcitatory reflexes are augmented. We also determined whether their final common pathway, glutamatergic activation of the rostral ventrolateral medulla (RVLM), was enhanced in male OZR compared with lean Zucker rats (LZR). Sciatic nerve stimulation or activation of the nasopharyngeal reflex evoked larger rises in splanchnic sympathetic nerve activity (SNA) (79% and 45% larger in OZR, respectively; P < 0.05) and MAP in urethane-anesthetized, ventilated, paralyzed adult OZR compared with LZR. After elimination of baroreflex feedback by pharmacological prevention of changes in MAP and heart rate, these two sympathoexcitatory reflexes were still exaggerated in OZR (167% and 69% larger, respectively, P < 0.05). In adult OZR microinjections of glutamate, AMPA, or NMDA into the RVLM produced larger rises in SNA (~61% larger in OZR, P < 0.05 for each drug) and MAP, but stimulation of axonal fibers in the upper thoracic spinal cord yielded equivalent responses in OZR and LZR. In juvenile OZR and LZR, sympathoexcitatory reflexes and physiological responses to RVLM activation were comparable. These data suggest that the ability of glutamate to activate the RVLM becomes enhanced in adult OZR and may contribute to the development of exaggerated sympathoexcitatory responses independent of impaired baroreflexes. PMID- 27280430 TI - "You are what you drink!" Focus on "Rehydration with soft drink-like beverages exacerbates dehydration and worsens dehydration-associated renal injury". PMID- 27280428 TI - Restoring placental growth factor-soluble fms-like tyrosine kinase-1 balance reverses vascular hyper-reactivity and hypertension in pregnancy. AB - Preeclampsia (PE) is a pregnancy-related hypertensive disorder (HTN-Preg) with unclear mechanism. An imbalance between antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and angiogenic placental growth factor (PlGF) has been observed in PE, but the vascular targets and signaling pathways involved are unclear. We assessed the extent of sFlt-1/PlGF imbalance and vascular dysfunction in a rat model of HTN-Preg produced by reduction of uteroplacental perfusion pressure (RUPP), and tested whether inducing a comparable sFlt-1/PlGF imbalance by infusing sFlt-1 (10 MUg.kg(-1).day(-1)) in day 14 pregnant (Preg) rats cause similar increases in blood pressure (BP) and vascular reactivity. Using these guiding measurements, we then tested whether restoring sFlt-1/PlGF balance by infusing PIGF (20 MUg.kg(-1).day(-1)) in RUPP rats would improve BP and vascular function. On gestational day 19, BP was in Preg+sFlt-1 and RUPP > Preg, and in RUPP+PlGF < RUPP rats. Plasma sFlt-1/PlGF ratio was increased in Preg+sFlt-1, and RUPP and was reduced in RUPP+PlGF rats. In isolated endothelium-intact aorta, carotid, mesenteric, and renal artery, phenylephrine (Phe)- and high KCl-induced contraction was in Preg+sFlt-1 and RUPP > Preg, and in RUPP+PlGF < RUPP. The differences in vascular reactivity to Phe and KCl between groups were less apparent in vessels treated with the nitric oxide synthase (NOS) inhibitor l-NAME or guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or endothelium-denuded, suggesting changes in endothelial NO-cGMP pathway. In Phe precontracted vessels, ACh-induced relaxation was in Preg+sFlt-1 and RUPP < Preg, and in RUPP+PlGF > RUPP, and was blocked by N(omega)-nitro-l-arginine methyl ester (l-NAME) or ODQ treatment or endothelium removal. Western blots revealed that aortic total endothelial NOS (eNOS) and activated phosphorylated-eNOS were in Preg+sFlt-1 and RUPP < Preg and in RUPP+PlGF > RUPP. ACh-induced vascular nitrate/nitrite production was in Preg+sFlt-1 and RUPP < Preg, and in RUPP+PlGF > RUPP. Vascular relaxation to the exogenous NO donor sodium nitroprusside was not different among groups. Thus, a tilt in the angiogenic balance toward anti angiogenic sFlt-1 is associated with decreased vascular relaxation and increased vasoconstriction and BP. Restoring the angiogenic/antiangiogenic balance using PlGF enhances endothelial NO-cGMP vascular relaxation and decreases vasoconstriction and BP in HTN-Preg rats and could offer a new approach in the management of PE. PMID- 27280429 TI - Components of the cannabinoid system in the dorsal periaqueductal gray are related to resting heart rate. AB - The present study was undertaken to examine whether variations in endocannabinoid signaling in the dorsal periaqueductal gray (dPAG) are associated with baseline autonomic nerve activity, heart rate, and blood pressure. Blood pressure was recorded telemetrically in rats, and heart rate and power spectral analysis of heart rate variability were determined. Natural variations from animal to animal provided a range of baseline values for analysis. Transcript levels of endocannabinoid signaling components in the dPAG were analyzed, and endocannabinoid content and catabolic enzyme activity were measured. Higher baseline heart rate was associated with increased anandamide content and with decreased activity of the anandamide-hydrolyzing enzyme, fatty acid amide hydrolase (FAAH), and it was negatively correlated with transcript levels of both FAAH and monoacylglycerol lipase (MAGL), a catabolic enzyme for 2 arachidonoylglycerol (2-AG). Autonomic tone and heart rate, but not blood pressure, were correlated to levels of FAAH mRNA. In accordance with these data, exogenous anandamide in the dPAG of anesthetized rats increased heart rate. These data indicate that in the dPAG, anandamide, a FAAH-regulated lipid, contributes to regulation of baseline heart rate through influences on autonomic outflow. PMID- 27280431 TI - Differential glucose metabolism in mice and humans affected by McArdle disease. AB - McArdle disease (muscle glycogenosis type V) is a disease caused by myophosphorylase deficiency leading to "blocked" glycogen breakdown. A significant but varying glycogen accumulation in especially distal hind limb muscles of mice affected by McArdle disease has recently been demonstrated. In this study, we investigated how myophosphorylase deficiency affects glucose metabolism in hind limb muscle of 20-wk-old McArdle mice and vastus lateralis muscles from patients with McArdle disease. Western blot analysis and activity assay demonstrated that glycogen synthase was inhibited in glycolytic muscle from McArdle mice. The level and activation of proteins involved in contraction induced glucose transport (AMPK, GLUT4) and glycogen synthase inhibition were increased in quadriceps muscle of McArdle mice. In addition, pCaMKII in quadriceps was reduced, suggesting lower insulin-induced glucose uptake, which could lead to lower glycogen accumulation. In comparison, tibialis anterior, extensor digitorum longus, and soleus had massive glycogen accumulation, but few, if any, changes or adaptations in glucose metabolism compared with wild-type mice. The findings suggest plasticity in glycogen metabolism in the McArdle mouse that is related to myosin heavy chain type IIB content in muscles. In patients, the level of GLUT4 was vastly increased, as were hexokinase II and phosphofructokinase, and glycogen synthase was more inhibited, suggesting that patients adapt by increasing capture of glucose for direct metabolism, thereby significantly reducing glycogen buildup compared with the mouse model. Hence, the McArdle mouse may be a useful tool for further comparative studies of disease mechanism caused by myophosphorylase deficiency and basic studies of metabolic adaptation in muscle. PMID- 27280433 TI - Cardiac oxygen limitation during an acute thermal challenge in the European perch: effects of chronic environmental warming and experimental hyperoxia. AB - Oxygen supply to the heart has been hypothesized to limit cardiac performance and whole animal acute thermal tolerance (CTmax) in fish. We tested these hypotheses by continuously measuring venous oxygen tension (Pvo2) and cardiovascular variables in vivo during acute warming in European perch (Perca fluviatilis) from a reference area during summer (18 degrees C) and a chronically heated area (Biotest enclosure) that receives warm effluent water from a nuclear power plant and is normally 5-10 degrees C above ambient (24 degrees C at the time of experiments). While CTmax was 2.2 degrees C higher in Biotest compared with reference perch, the peaks in cardiac output and heart rate prior to CTmax occurred at statistically similar Pvo2 values (2.3-4.0 kPa), suggesting that cardiac failure occurred at a common critical Pvo2 threshold. Environmental hyperoxia (200% air saturation) increased Pvo2 across temperatures in reference fish, but heart rate still declined at a similar temperature. CTmax of reference fish increased slightly (by 0.9 degrees C) in hyperoxia, but remained significantly lower than in Biotest fish despite an improved cardiac output due to an elevated stroke volume. Thus, while cardiac oxygen supply appears critical to elevate stroke volume at high temperatures, oxygen limitation may not explain the bradycardia and arrhythmia that occur prior to CTmax Acute thermal tolerance and its thermal plasticity can, therefore, only be partially attributed to cardiac failure from myocardial oxygen limitations, and likely involves limiting factors on multiple organizational levels. PMID- 27280434 TI - Shear wave dispersion behaviors of soft, vascularized tissues from the microchannel flow model. AB - The frequency dependent behavior of tissue stiffness and the dispersion of shear waves in tissue can be measured in a number of ways, using integrated imaging systems. The microchannel flow model, which considers the effects of fluid flow in the branching vasculature and microchannels of soft tissues, makes specific predictions about the nature of dispersion. In this paper we introduce a more general form of the 4 parameter equation for stress relaxation based on the microchannel flow model, and then derive the general frequency domain equation for the complex modulus. Dispersion measurements in liver (ex vivo) and whole perfused placenta (post-delivery) correspond to the predictions from theory, guided by independent stress relaxation measurements and consideration of the vascular tree structure. PMID- 27280435 TI - Degradation products of mangiferin by gamma irradiation with inhibitory effects on NO production. AB - The xanthone glucoside mangiferin (1) was converted by gamma-irradiation into three new compounds, mangiferdiol (2), mangiferinol (3), and isomangiferinol (4). The new compound 2 containing two hydroxymethyl groups instead of a ketone moiety exhibited significantly improved inhibitory activity against nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 value 47.1 +/- 1.7 MUM, compared to the mother mangiferin. PMID- 27280432 TI - Independent effects of early-life experience and trait aggression on cardiovascular function. AB - Early-life experience (ELE) can significantly affect life-long health and disease, including cardiovascular function. Specific dimensions of emotionality also modify risk of disease, and aggressive traits along with social inhibition have been established as independent vulnerability factors for the progression of cardiovascular disease. Yet, the biological mechanisms mediating these associations remain poorly understood. The present study utilized the inherently stress-susceptible and socially inhibited Wistar-Kyoto rats to determine the potential influences of ELE and trait aggression (TA) on cardiovascular parameters throughout the lifespan. Pups were exposed to maternal separation (MS), consisting of daily 3-h separations of the entire litter from postnatal day (P)1 to P14. The rats were weaned at P21, and as adults were instrumented for chronic radiotelemetry recordings of blood pressure and heart rate (HR). Adult aggressive behavior was assessed using the resident-intruder test, which demonstrated that TA was independent of MS exposure. MS-exposed animals (irrespective of TA) had significantly lower resting HR accompanied by increases in HR variability. No effects of MS on resting blood pressure were detected. In contrast, TA correlated with increased resting mean, systolic, and diastolic arterial pressures but had no effect on HR. TA rats (relative to nonaggressive animals) also manifested increased wall-to-lumen ratio in the thoracic aorta, increased sensitivity to phenylephrine-induced vascular contractility, and increased norepinephrine content in the heart. Together these data suggest that ELE and TA are independent factors that impact baseline cardiovascular function. PMID- 27280436 TI - Optimization of Cyclic Plasmin Inhibitors: From Benzamidines to Benzylamines. AB - New macrocyclic plasmin inhibitors based on our previously optimized P2-P3 core segment have been developed. In the first series, the P4 residue was modified, whereas the 4-amidinobenzylamide in P1 position was maintained. The originally used P4 benzylsulfonyl residue could be replaced by various sulfonyl- or urethane like protecting groups. In the second series, the P1 benzamidine was modified and a strong potency and excellent selectivity was retained by incorporation of p xylenediamine. Several analogues inhibit plasmin in the subnanomolar range, and their potency against related trypsin-like serine proteases including trypsin itself could be further reduced. Selected derivatives have been tested in a plasma fibrinolysis assay and are more effective than the reference inhibitor aprotinin. The crystal structure of one inhibitor was determined in complex with trypsin. The binding mode reveals a sterical clash of the inhibitor's linker segment with the 99-hairpin loop of trypsin, which is absent in plasmin. PMID- 27280437 TI - Cancer Stem Cells - Are Surface Markers Alone Sufficient? AB - The identification of Cancer Stem Cells (CSCs) in leukemia has opened a new field in cancer research. This has led to the identification of similar cells in other types of cancer. CSCs express distinct surface markers and functional properties which distinguish them from the rest of the cells within a tumor. Due to variability in identification of CSCs in a particular type of cancer (except brain, breast and leukemia), surface markers alone may not be sufficient. It is critical to identify and isolate this small population of cells from the heterogeneous tumors to understand their pathogenesis. Identification of surface markers together with intrinsic properties of CSCs like colony formation, Hoechst exclusion or ALDEFLUOR assay may be useful in isolating more primitive and highly pure CSCs from a heterogeneous population of malignant cells. This review critically analyses various techniques and methods along with their advantages and disadvantages that are employed in identifying CSCs from different types of cancers. PMID- 27280438 TI - Isolation and Characterization of an Atypical Metschnikowia sp. Strain from the Skin Scraping of a Dermatitis Patient. AB - A yeast-like organism was isolated from the skin scraping sample of a stasis dermatitis patient in the Mycology Unit Department of Medical Microbiology, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia. The isolate produced no pigment and was not identifiable using chromogenic agar and API 20C AUX. The fungus was identified as Metschnikowia sp. strain UM 1034, which is close to that of Metschnikowia drosophilae based on ITS- and D1/D2 domain-based phylogenetic analysis. However, the physiology of the strain was not associated to M. drosophilae. This pathogen exhibited low sensitivity to all tested azoles, echinocandins, 5-flucytosine and amphotericin B. This study provided insight into Metschnikowia sp. strain UM 1034 phenotype profiles using a Biolog phenotypic microarray (PM). The isolate utilized 373 nutrients of 760 nutrient sources and could adapt to a broad range of osmotic and pH environments. To our knowledge, this is the first report of the isolation of Metschnikowia non-pulcherrima sp. from skin scraping, revealing this rare yeast species as a potential human pathogen that may be misidentified as Candida sp. using conventional methods. Metschnikowia sp. strain UM 1034 can survive in flexible and diverse environments with a generalist lifestyle. PMID- 27280439 TI - Influence of Tumor Microenvironment on the Distribution and Elimination of Nano formulations. AB - OBJECTIVE: To give an in-depth overview about the tumor and its surrounding microenvironment influencing distribution and elimination of nanoformulations. Mehtods: This up-to-date review will summarize the microenvironmental components and their influence on the various factors related to nanoformulations and tumor which affect the penetration, distribution, regulation and clearance of nanoformulations from the tumor cells. Results of recent advances in miroenvironmental tuning with nanoformulations will be evaluated mechanistically. In addition, those natures of tumors involving enhanced cancer therapy will be discussed. Finally, strategies of nanoparticulate design and decoration to achieve efficient drug delivery are presented. RESULTS: Development of tumor is facilitated by its surrounding microenvironment and is regulated by different extra and intracellular components. Drug-loaded nanoformulations are mainly administered via oral and parenteral routes which reach tumor cells via different mechanisms. Chemotherapeutics get diffused from circulation into the surrounding microenvironment which latter get internalized into the cellular interstial area by passive diffusion mechanism due to virtue of size, charge, and pegylation effects, or by ligands and receptor mediated, or through enhanced permeability and retention effects through leaky apertures. Due to mildly acidic environment and hypoxic interstial environment, the influx of nanoformulations is hindered. The metabolites of the nanoformulations get diffused out from the tumor cells as a results of high interstial fluid pressure and get cleared either via liver or via renal execration. CONCLUSION: Well-understanding tumoral microenvironments which significantly affect distribution and elimination of nanoformulations is essential for engineering delivery systems with superior anti-tumoral effect. PMID- 27280440 TI - The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation. AB - DEAD-box proteins are ubiquitous regulators of RNA biology. While commonly dubbed "helicases," their activities also include duplex annealing, adenosine triphosphate (ATP)-dependent RNA binding, and RNA-protein complex remodeling. Rok1, an essential DEAD-box protein, and its cofactor Rrp5 are required for ribosome assembly. Here, we use in vivo and in vitro biochemical analyses to demonstrate that ATP-bound Rok1, but not adenosine diphosphate (ADP)-bound Rok1, stabilizes Rrp5 binding to 40S ribosomes. Interconversion between these two forms by ATP hydrolysis is required for release of Rrp5 from pre-40S ribosomes in vivo, thereby allowing Rrp5 to carry out its role in 60S subunit assembly. Furthermore, our data also strongly suggest that the previously described accumulation of snR30 upon Rok1 inactivation arises because Rrp5 release is blocked and implicate a previously undescribed interaction between Rrp5 and the DEAD-box protein Has1 in mediating snR30 accumulation when Rrp5 release from pre-40S subunits is blocked. PMID- 27280441 TI - Molecular Evolution and Phylodynamics of Acute Hepatitis B Virus in Japan. AB - Hepatitis B virus (HBV) is prevalent worldwide and causes liver diseases, including acute and chronic hepatitis. Ten HBV genotypes (A-J) with distinct geographic distributions have been reported. Cases of acute HBV infection with genotype A have increased in Japan nationwide since the 1990s, mainly through sexual transmission. To investigate the molecular evolution and phylodynamics of HBV genotypes, we collected acute HBV isolates acquired in Japan from 1992-2002. Full genomes were obtained for comprehensive phylogenetic and phylodynamic analysis, with other Japanese HBV sequences from GenBank that were isolated during 1991-2010. HBV genotypes were classified using the maximum-likelihood and Bayesian methods. The GMRF Bayesian Skyride was used to estimate the evolution and population dynamics of HBV. Four HBV genotypes (A, B, C, and H) were identified, of which C was the major genotype. The phylodynamic results indicated an exponential growth between the 1960s and early 1990s; this was followed by a population bottleneck after 1995, possibly linked with successful implementation of a nationwide vaccination program. However, HBV/A increased from 1990 to 2003 2004, and then started to decrease. The prevalence of genotype A has increased over the past 10 years. Phylodynamic inference clearly demonstrates a steady population growth compatible with an ongoing subepidemic; this might be due to the loss of immunity to HBV in adolescents and people being born before the vaccination program. This is the first phylodynamic study of HBV infection in Japan and will facilitate understanding the molecular epidemiology and long-term evolutionary dynamics of this virus in Japan. PMID- 27280442 TI - Differential Incorporation of Carbon Substrates among Microbial Populations Identified by Field-Based, DNA Stable-Isotope Probing in South China Sea. AB - To determine the adapted microbial populations to variant dissolved organic carbon (DOC) sources in the marine environment and improve the understanding of the interaction between microorganisms and marine DOC pool, field-based incubation experiments were carried out using supplemental 13C-labeled typical substrates D-glucose and D-glucosamine (D-Glc and D-GlcN, respectively), which are two important components in marine DOC pool in the South China Sea. 13C- and 12C-DNA were then fractionated by ultracentrifugation and the microbial community was analyzed by terminal-restriction fragment length polymorphism and 454 pyrosequencing of 16S rRNA gene. 12C-DNA-based communities showed relatively high similarities with their corresponding in situ communities, and their bacterial diversities were generally higher than 13C-DNA-based counterparts. Distinct differences in community composition were found between 13C- and 12C-DNA-based communities and between two substrate-supplemented 13C-DNA-based communities; these differences distinctly varied with depth and site. In most cases, there were more genera with relative abundances of >0.1% in D-Glc-incorporating communities than in D-GlcN-incorporating communities. The Roseobacter clade was one of the prominent actively substrate-incorporating bacterial populations in all 13C-DNA-based communities. Vibrio was another prominent actively D-GlcN incorporating bacterial population in most incubations. However notably, different OTUs dominated this clade or genus in different treatments at different depths. Altogether, these results suggested that there were taxa-specific differences in DOC assimilations and, moreover, their differences varied among the typical water masses, which could have been caused by the variant compositions of original bacterial communities from different hydrological environments. This implies that ecologically, the levels of labile or recalcitrance of DOC can be maintained only in a specific environmental context with specific bacterial community composition. PMID- 27280444 TI - HCV-Mediated Apoptosis of Hepatocytes in Culture and Viral Pathogenesis. AB - Chronic Hepatitis C Virus (HCV) infection is associated with progressive liver injury and subsequent development of fibrosis and cirrhosis. The death of hepatocytes results in the release of cytokines that induce inflammatory and fibrotic responses. The mechanism of liver damage is still under investigation but both apoptosis and immune-mediated processes may play roles. By observing the changes in gene expression patterns in HCV-infected cells, both markers and the causes of HCV-associated liver injury may be elucidated. HCV genotype 1b virus from persistently infected VeroE6 cells induced a strong cytopathic effect when used to infect Huh7.5 hepatoma cells. To determine if this cytopathic effect was a result of apoptosis, ultrastructural changes were observed by electron microscopy and markers of programmed cell death were surveyed. Screening of a human PCR array demonstrated a gene expression profile that contained upregulated markers of apoptosis, including tumor necrosis factor, caspases and caspase activators, Fas, Bcl2-interacting killer (BIK) and tumor suppressor protein, p53, as a result of HCV genotype 1b infection. The genes identified in this study should provide new insights into understanding viral pathogenesis in liver cells and may possibly help to identify novel antiviral and antifibrotic targets. PMID- 27280443 TI - The Drosophila ETV5 Homologue Ets96B: Molecular Link between Obesity and Bipolar Disorder. AB - Several reports suggest obesity and bipolar disorder (BD) share some physiological and behavioural similarities. For instance, obese individuals are more impulsive and have heightened reward responsiveness, phenotypes associated with BD, while bipolar patients become obese at a higher rate and earlier age than people without BD; however, the molecular mechanisms of such an association remain obscure. Here we demonstrate, using whole transcriptome analysis, that Drosophila Ets96B, homologue of obesity-linked gene ETV5, regulates cellular systems associated with obesity and BD. Consistent with a role in obesity and BD, loss of nervous system Ets96B during development increases triacylglyceride concentration, while inducing a heightened startle-response, as well as increasing hyperactivity and reducing sleep. Of notable interest, mouse Etv5 and Drosophila Ets96B are expressed in dopaminergic-rich regions, and loss of Ets96B specifically in dopaminergic neurons recapitulates the metabolic and behavioural phenotypes. Moreover, our data indicate Ets96B inhibits dopaminergic-specific neuroprotective systems. Additionally, we reveal that multiple SNPs in human ETV5 link to body mass index (BMI) and BD, providing further evidence for ETV5 as an important and novel molecular intermediate between obesity and BD. We identify a novel molecular link between obesity and bipolar disorder. The Drosophila ETV5 homologue Ets96B regulates the expression of cellular systems with links to obesity and behaviour, including the expression of a conserved endoplasmic reticulum molecular chaperone complex known to be neuroprotective. Finally, a connection between the obesity-linked gene ETV5 and bipolar disorder emphasizes a functional relationship between obesity and BD at the molecular level. PMID- 27280445 TI - Molecular and Morpho-Agronomical Characterization of Root Architecture at Seedling and Reproductive Stages for Drought Tolerance in Wheat. AB - Water availability is a major limiting factor for wheat (Triticum aestivum L.) production in rain-fed agricultural systems worldwide. Root architecture is important for water and nutrition acquisition for all crops, including wheat. A set of 158 diverse wheat genotypes of Australian (72) and Indian (86) origin were studied for morpho-agronomical traits in field under irrigated and drought stress conditions during 2010-11 and 2011-12.Out of these 31 Indian wheat genotypes comprising 28 hexaploid (Triticum aestivum L.) and 3 tetraploid (T. durum) were characterized for root traits at reproductive stage in polyvinyl chloride (PVC) pipes. Roots of drought tolerant genotypes grew upto137cm (C306) as compared to sensitive one of 63cm with a mean value of 94.8cm. Root architecture traits of four drought tolerant (C306, HW2004, HD2888 and NI5439) and drought sensitive (HD2877, HD2012, HD2851 and MACS2496) genotypes were also observed at 6 and 9 days old seedling stage. The genotypes did not show any significant variation for root traits except for longer coleoptiles and shoot and higher absorptive surface area in drought tolerant genotypes. The visible evaluation of root images using WinRhizo Tron root scanner of drought tolerant genotype HW2004 indicated compact root system with longer depth while drought sensitive genotype HD2877 exhibited higher horizontal root spread and less depth at reproductive stage. Thirty SSR markers were used to study genetic variation which ranged from 0.12 to 0.77 with an average value of 0.57. The genotypes were categorized into three subgroups as highly tolerant, sensitive, moderately sensitive and tolerant as intermediate group based on UPGMA cluster, STRUCTURE and principal coordinate analyses. The genotypic clustering was positively correlated to grouping based on root and morpho-agronomical traits. The genetic variability identified in current study demonstrated these traits can be used to improve drought tolerance and association mapping. PMID- 27280447 TI - Biologic Data of Cynomolgus Monkeys Maintained under Laboratory Conditions. AB - The cynomolgus monkey (Macaca fascicularis) is a well-known non-human primate species commonly used in non-clinical research. It is important to know basal clinical pathology parameters in order to have a reference for evaluating any potential treatment-induced effects, maintaining health status among animals and, if needed, evaluating correct substantiative therapies. In this study, data from 238 untreated cynomolgus monkeys (119 males and 119 females of juvenile age, 2.5 to 3.5 years) kept under laboratory conditions were used to build up a reference database of clinical pathology parameters. Twenty-two hematology markers, 24 clinical chemistry markers and two blood coagulation parameters were analyzed. Gender-related differences were evaluated using statistical analyses. To assess the possible effects of stress induced by housing or handling involved in treatment procedures, 78 animals (35 males and 35 females out of 238 juvenile monkeys and four adult males and four adult females) were used to evaluate cortisol, corticosterone and behavioral assessment over time. Data were analyzed using a non-parametric statistical test and machine learning approaches. Reference clinical pathology data obtained from untreated animals may be extremely useful for investigators employing cynomolgus monkeys as a test system for non-clinical safety studies. PMID- 27280448 TI - Bayesian analysis of factorial designs. AB - This article provides a Bayes factor approach to multiway analysis of variance (ANOVA) that allows researchers to state graded evidence for effects or invariances as determined by the data. ANOVA is conceptualized as a hierarchical model where levels are clustered within factors. The development is comprehensive in that it includes Bayes factors for fixed and random effects and for within subjects, between-subjects, and mixed designs. Different model construction and comparison strategies are discussed, and an example is provided. We show how Bayes factors may be computed with BayesFactor package in R and with the JASP statistical package. (PsycINFO Database Record PMID- 27280446 TI - Replication and Characterization of Association between ABO SNPs and Red Blood Cell Traits by Meta-Analysis in Europeans. AB - Red blood cell (RBC) traits are routinely measured in clinical practice as important markers of health. Deviations from the physiological ranges are usually a sign of disease, although variation between healthy individuals also occurs, at least partly due to genetic factors. Recent large scale genetic studies identified loci associated with one or more of these traits; further characterization of known loci and identification of new loci is necessary to better understand their role in health and disease and to identify potential molecular mechanisms. We performed meta-analysis of Metabochip association results for six RBC traits-hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV) and red blood cell count (RCC)-in 11 093 Europeans from seven studies of the UCL-LSHTM-Edinburgh-Bristol (UCLEB) Consortium. We identified 394 non-overlapping SNPs in five loci at genome-wide significance: 6p22.1-6p21.33 (with HFE among others), 6q23.2 (with HBS1L among others), 6q23.3 (contains no genes), 9q34.3 (only ABO gene) and 22q13.1 (with TMPRSS6 among others), replicating previous findings of association with RBC traits at these loci and extending them by imputation to 1000 Genomes. We further characterized associations between ABO SNPs and three traits: hemoglobin, hematocrit and red blood cell count, replicating them in an independent cohort. Conditional analyses indicated the independent association of each of these traits with ABO SNPs and a role for blood group O in mediating the association. The 15 most significant RBC associated ABO SNPs were also associated with five cardiometabolic traits, with discordance in the direction of effect between groups of traits, suggesting that ABO may act through more than one mechanism to influence cardiometabolic risk. PMID- 27280449 TI - The association between adverse childhood experiences (ACEs) and suicide attempts in a population-based study. AB - OBJECTIVES: To further our understanding of the relationship between Adverse Childhood Experiences (ACEs) and suicidal behaviour, this study investigates the association between three types of ACEs and lifetime suicide attempts, while considering potential gender-specific and mediating effects. METHODS: Data were obtained from the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH), a cross-sectional, population-based survey comprised of respondents aged 18 or older who provided self-reported data on past experiences of suicide attempts, as well as childhood sexual abuse (CSA), childhood physical abuse (CPA) and parental domestic violence (PDV) (n = 22 559). After testing for ACE by gender interactions, we estimated the odds of lifetime suicide attempts for each ACE and then investigated whether depression, anxiety, substance abuse and chronic pain acted as mediators of the relationship. RESULTS: The odds of suicide attempts are significantly higher among those with a history of CPA (OR = 3.29; 99.9% CI 2.33 4.64), CSA (OR = 4.42; 99.9% CI 3.14-6.23) or PDV (OR = 2.52; 99.9% CI 1.69 3.76), when ACEs are mutually adjusted. There is little evidence that gender acts as a moderator; however, depression, anxiety, substance abuse and chronic pain appear to partially mediate the associations. Depression alone accounts for about a quarter of the associations with CSA and CPA. CONCLUSIONS: Mental health factors and chronic pain appear only to partially mediate relationships between ACEs and lifetime suicide attempts. Future research should look at other pathways with the goal of developing multi-level interventions. PMID- 27280450 TI - Exploring the Measurement of Markedness and Its Relationship with Other Linguistic Variables. AB - Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse. PMID- 27280451 TI - Association between Molar Incisor Hypomineralization in Schoolchildren and Both Prenatal and Postnatal Factors: A Population-Based Study. AB - BACKGROUND: Although studies throughout the world have investigated potential factors involved in the occurrence of molar incisor hypomineralization (MIH), the findings are varied and inconclusive. OBJECTIVE: The aim of the present study was to evaluate the prevalence of MIH and identify associated prenatal, perinatal and postnatal factors among Brazilian schoolchildren aged 8 and 9 years. METHODS: A cross-sectional study was conducted with a randomly selected population-based sample of 1181 schoolchildren. Information on demographic and socioeconomic characteristics as well as prenatal, perinatal and postnatal aspects was obtained through questionnaires. The clinical examination included the investigation of MIH based on the criteria of the European Academy of Paediatric Dentistry. Dental caries in the permanent dentition and developmental defects of enamel (DDE) on the primary second molars were also recorded. Data analysis involved descriptive statistics, bivariate tests and Poisson regression with robust variance. RESULTS: The prevalence of MIH was 20.4%. MIH was more frequent among children with dental caries in the permanent dentition (PR: 2.67; 95% CI: 1.98-3.61), those with DDE on the primary second molars (PR: 2.54; 95% CI: 1.87-3.45) and those who experienced asthma/bronchitis in the first four years of life (PR: 1.93; 95% CI: 1.45-2.56). CONCLUSIONS: The prevalence of MIH was high and was associated with dental caries, the presence of DDE on primary second molars and the experience of asthma/bronchitis in early life. These findings could be useful in the identification of children in need of shorter recall intervals to prevent the consequences of MIH, such as enamel breakdown dental caries. PMID- 27280453 TI - The Psychometric Properties of a Modified Sit-to-Stand Test With Use of the Upper Extremities in Institutionalized Older Adults. AB - Current sit-to-stand protocols do not permit use of upper extremities, limiting the protocols' utility for institutionalized older adults with diminished physical function. The objective of this study was to modify a 30-s sit-to-stand protocol to allow for arm use and to examine test-retest reliability and convergent validity; 54 institutionalized older adult men (age = 91 +/- 3 year) performed the 30-s sit-to-stand twice within a span of 3 to 7 days. Results suggest good test-retest reliability (intraclass correlation coefficient = .84) and convergent validity with the Timed Up and Go Test (r = -.62). This modified 30-s sit-to-stand can be used to assess physical function performance in institutionalized older adults and will ensure that individuals with lower physical function capacity can complete the test, thus eliminating the floor effect demonstrated with other sit-to-stand protocols. PMID- 27280454 TI - Next-Generation Mitogenomics: A Comparison of Approaches Applied to Caecilian Amphibian Phylogeny. AB - Mitochondrial genome (mitogenome) sequences are being generated with increasing speed due to the advances of next-generation sequencing (NGS) technology and associated analytical tools. However, detailed comparisons to explore the utility of alternative NGS approaches applied to the same taxa have not been undertaken. We compared a 'traditional' Sanger sequencing method with two NGS approaches (shotgun sequencing and non-indexed, multiplex amplicon sequencing) on four different sequencing platforms (Illumina's HiSeq and MiSeq, Roche's 454 GS FLX, and Life Technologies' Ion Torrent) to produce seven (near-) complete mitogenomes from six species that form a small radiation of caecilian amphibians from the Seychelles. The fastest, most accurate method of obtaining mitogenome sequences that we tested was direct sequencing of genomic DNA (shotgun sequencing) using the MiSeq platform. Bayesian inference and maximum likelihood analyses using seven different partitioning strategies were unable to resolve compellingly all phylogenetic relationships among the Seychelles caecilian species, indicating the need for additional data in this case. PMID- 27280452 TI - Auditory Hallucinations and the Brain's Resting-State Networks: Findings and Methodological Observations. AB - In recent years, there has been increasing interest in the potential for alterations to the brain's resting-state networks (RSNs) to explain various kinds of psychopathology. RSNs provide an intriguing new explanatory framework for hallucinations, which can occur in different modalities and population groups, but which remain poorly understood. This collaboration from the International Consortium on Hallucination Research (ICHR) reports on the evidence linking resting-state alterations to auditory hallucinations (AH) and provides a critical appraisal of the methodological approaches used in this area. In the report, we describe findings from resting connectivity fMRI in AH (in schizophrenia and nonclinical individuals) and compare them with findings from neurophysiological research, structural MRI, and research on visual hallucinations (VH). In AH, various studies show resting connectivity differences in left-hemisphere auditory and language regions, as well as atypical interaction of the default mode network and RSNs linked to cognitive control and salience. As the latter are also evident in studies of VH, this points to a domain-general mechanism for hallucinations alongside modality-specific changes to RSNs in different sensory regions. However, we also observed high methodological heterogeneity in the current literature, affecting the ability to make clear comparisons between studies. To address this, we provide some methodological recommendations and options for future research on the resting state and hallucinations. PMID- 27280456 TI - Rapid processing of PET list-mode data for efficient uncertainty estimation and data analysis. AB - In this technical note we propose a rapid and scalable software solution for the processing of PET list-mode data, which allows the efficient integration of list mode data processing into the workflow of image reconstruction and analysis. All processing is performed on the graphics processing unit (GPU), making use of streamed and concurrent kernel execution together with data transfers between disk and CPU memory as well as CPU and GPU memory. This approach leads to fast generation of multiple bootstrap realisations, and when combined with fast image reconstruction and analysis, it enables assessment of uncertainties of any image statistic and of any component of the image generation process (e.g. random correction, image processing) within reasonable time frames (e.g. within five minutes per realisation). This is of particular value when handling complex chains of image generation and processing. The software outputs the following: (1) estimate of expected random event data for noise reduction; (2) dynamic prompt and random sinograms of span-1 and span-11 and (3) variance estimates based on multiple bootstrap realisations of (1) and (2) assuming reasonable count levels for acceptable accuracy. In addition, the software produces statistics and visualisations for immediate quality control and crude motion detection, such as: (1) count rate curves; (2) centre of mass plots of the radiodistribution for motion detection; (3) video of dynamic projection views for fast visual list-mode skimming and inspection; (4) full normalisation factor sinograms. To demonstrate the software, we present an example of the above processing for fast uncertainty estimation of regional SUVR (standard uptake value ratio) calculation for a single PET scan of (18)F-florbetapir using the Siemens Biograph mMR scanner. PMID- 27280455 TI - Potassium Measures and Their Associations with Glucose and Diabetes Risk: The Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: Recent studies have found low-normal potassium (K) to be associated with increased diabetes risk. We sought to verify these associations in a multi ethnic US cohort; and to determine if these associations extend to US Hispanics and Asian-Americans. METHODS: We analyzed data from Multi-Ethnic Study of Atherosclerosis (MESA) participants who were free-of-diabetes at baseline. We examined cross-sectional associations between measures of K-serum, dietary, and urine-with fasting glucose and HOMA-IR. We examined longitudinal associations between K and diabetes risk over 8 years. FINDINGS: In multivariable models, compared to those with higher serum K (>=4.5mmol/L), those with lower serum K (<4.0mmol/L) had significantly higher fasting glucose [1.3 mg/dL (95%CI 0.2, 2.4), P-value = 0.03]. Incident diabetes developed in 1281 of 5415 at-risk participants. In minimally-adjusted models, we found inverse associations between serum and dietary K and diabetes risk. Compared to those with higher serum K, those with lower serum K had an HR (95% CI) of incident diabetes of 1.23 (1.04, 1.47), P-value = 0.02. However, these associations were attenuated in fully adjusted models. We found no significant interaction between potassium and ethnicity. CONCLUSIONS: In this multi-ethnic cohort, we found a significant inverse association between serum K and fasting glucose but no significant association with longer-term diabetes risk. This inverse association between potassium and glucose must be studied further to understand the physiology and its potential impact on chronic health. PMID- 27280463 TI - A Method for Quantifying, Visualising, and Analysing Gastropod Shell Form. AB - Quantitative analysis of organismal form is an important component for almost every branch of biology. Although generally considered an easily-measurable structure, the quantification of gastropod shell form is still a challenge because many shells lack homologous structures and have a spiral form that is difficult to capture with linear measurements. In view of this, we adopt the idea of theoretical modelling of shell form, in which the shell form is the product of aperture ontogeny profiles in terms of aperture growth trajectory that is quantified as curvature and torsion, and of aperture form that is represented by size and shape. We develop a workflow for the analysis of shell forms based on the aperture ontogeny profile, starting from the procedure of data preparation (retopologising the shell model), via data acquisition (calculation of aperture growth trajectory, aperture form and ontogeny axis), and data presentation (qualitative comparison between shell forms) and ending with data analysis (quantitative comparison between shell forms). We evaluate our methods on representative shells of the genera Opisthostoma and Plectostoma, which exhibit great variability in shell form. The outcome suggests that our method is a robust, reproducible, and versatile approach for the analysis of shell form. Finally, we propose several potential applications of our methods in functional morphology, theoretical modelling, taxonomy, and evolutionary biology. PMID- 27280465 TI - Synthetic and Medicinal Prospective of Structurally Modified Curcumins. AB - Curcumin, a natural yellow phenolic compound, is present in various types of herbs, particularly in Turmeric, Curcuma longa Linn. (Zingiberaceae family) rhizomes. Curcumin is a polyphenolic natural compound with diverse and attractive biological activities. In the last decade curcumine and its various synthetic analogues have been prepared and evaluated for various pharmacological activities that prove it as a lead molecule against several biological targets. It is a natural antioxidant and exhibited many pharmacological activities such as anti inflammatory, anti-microbial, anticancer, anti-Alzheimer in both preclinical and clinical studies. Moreover, Curcumin and its analogues have anti-tubercular, cardioprotective, anti-diabetic, hepatoprotective, neuroprotective, nephroprotective, antirheumatic and anti-viral activities. The substitutions of 1,6-heptadiene linkage moiety via carbonyl group sustituion and addition of heterocyclic linker; isoxazole, 1H-pyrazole, cyclopentanone, piperidin-4-one, N methylpiperidin-4-one enhance biological activities. The structure activity relationship of various curcumin analogues is studied for medicinal purposes and it reveals that monocarbonyl linkage analogues have anticancer properties. The current review gives an insight of the history, chemistry, analogues and most interesting in vitro and in vivo studies on the biological effects of Curcumin and its analogues. PMID- 27280464 TI - Regulation of Smoothened Phosphorylation and High-Level Hedgehog Signaling Activity by a Plasma Membrane Associated Kinase. AB - Hedgehog (Hh) signaling controls embryonic development and adult tissue homeostasis through the G protein coupled receptor (GPCR)-family protein Smoothened (Smo). Upon stimulation, Smo accumulates on the cell surface in Drosophila or primary cilia in vertebrates, which is thought to be essential for its activation and function, but the underlying mechanisms remain poorly understood. Here we show that Hh stimulates the binding of Smo to a plasma membrane-associated kinase Gilgamesh (Gish)/CK1gamma and that Gish fine-tunes Hh pathway activity by phosphorylating a Ser/Thr cluster (CL-II) in the juxtamembrane region of Smo carboxyl-terminal intracellular tail (C-tail). We find that CL-II phosphorylation is promoted by protein kinase A (PKA)-mediated phosphorylation of Smo C-tail and depends on cell surface localization of both Gish and Smo. Consistent with CL-II being critical for high-threshold Hh target gene expression, its phosphorylation appears to require higher levels of Hh or longer exposure to the same level of Hh than PKA-site phosphorylation on Smo. Furthermore, we find that vertebrate CK1gamma is localized at the primary cilium to promote Smo phosphorylation and Sonic hedgehog (Shh) pathway activation. Our study reveals a conserved mechanism whereby Hh induces a change in Smo subcellular localization to promote its association with and activation by a plasma membrane localized kinase, and provides new insight into how Hh morphogen progressively activates Smo. PMID- 27280466 TI - Mapping the spatiotemporal dynamics of processing task-relevant and task irrelevant sound feature changes using concurrent EEG-fMRI. AB - The cortical processing of changes in auditory input involves auditory sensory regions as well as different frontoparietal brain networks. The spatiotemporal dynamics of the activation spread across these networks has, however, not been investigated in detail so far. We here approached this issue using concurrent functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), providing us with simultaneous information on both the spatial and temporal patterns of change-related activity. We applied an auditory stimulus categorization task with switching categorization rules, allowing to analyze change-related responses as a function of the changing sound feature (pitch or duration) and the task relevance of the change. Our data show the successive progression of change-related activity from regions involved in early change detection to the ventral and dorsal attention networks, and finally the central executive network. While early change detection was found to recruit feature specific networks involving auditory sensory but also frontal and parietal brain regions, the later spread of activity across the frontoparietal attention and executive networks was largely independent of the changing sound feature, suggesting the existence of a general feature-independent processing pathway of change-related information. Task relevance did not modulate early auditory sensory processing, but was mainly found to affect processing in frontal brain regions. Hum Brain Mapp 37:3400-3416, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27280467 TI - The Effect of Strict Segregation on Pseudomonas aeruginosa in Cystic Fibrosis Patients. AB - INTRODUCTION: Segregation of patients with cystic fibrosis (CF) was implemented to prevent chronic infection with epidemic Pseudomonas aeruginosa strains with presumed detrimental clinical effects, but its effectiveness has not been carefully evaluated. METHODS: The effect of strict segregation on the incidence of P. aeruginosa infection in CF patients was investigated through longitudinal protocolized follow-up of respiratory tract infection before and after segregation. In two nested cross-sectional studies in 2007 and 2011 the P. aeruginosa population structure was investigated and clinical parameters were determined in patients with and without infection with the Dutch epidemic P. aeruginosa clone (ST406). RESULTS: Of 784 included patients 315 and 382 were at risk for acquiring chronic P. aeruginosa infection before and after segregation. Acquisition rates were, respectively, 0.14 and 0.05 per 1,000 days at risk (HR: 0.66, 95% CI [0.2548-1.541]; p = 0.28). An exploratory subgroup analysis indicated lower acquisition after segregation in children < 15 years of age (HR: 0.43, 95% CI[0.21-0.95]; p = 0.04). P. aeruginosa population structure did not change after segregation and ST406 was not associated with lung function decline, death or lung transplantation. CONCLUSIONS: Strict segregation was not associated with a statistically significant lower acquisition of chronic P. aeruginosa infection and ST406 was not associated with adverse clinical outcome. After segregation there were no new acquisitions of ST406. In an unplanned exploratory analysis chronic acquisition of P. aeruginosa was lower after implementation of segregation in patients under 15 years of age. PMID- 27280469 TI - Two variations of congenital epulis. PMID- 27280468 TI - Targeted Delivery of Deoxycytidine Kinase to Her2-Positive Cells Enhances the Efficacy of the Nucleoside Analog Fludarabine. AB - Cytotoxic drugs, such as nucleoside analogs and toxins, commonly suffer from off target effects. One approach to mitigate this problem is to deliver the cytotoxic drug selectively to the intended site. While for toxins this can be achieved by conjugating the cell-killing moiety to a targeting moiety, it is not an option for nucleoside analogs, which rely on intracellular enzymes to convert them to their active triphosphorylated form. To overcome this limitation, and achieve site-targeted activation of nucleoside analogs, we fused the coding region of a prodrug-activating enzyme, deoxycytidine kinase (dCK), to affinity reagents that bind to the Her2 cell surface protein. We evaluated dCK fusions to an anti-Her2 affibody and Designed Ankyrin Repeat Protein (DARPin) for their ability to kill cancer cells by promoting the activation of the nucleoside analog fludarabine. Cell staining and flow cytometry experiments with three Her2 positive cancer cell lines (BT-474-JB, JIMT-1 and SK-OV-3) indicate dCK fusions binding and cellular internalization. In contrast, these reagents bind only weakly to the Her2 negative cell line, MCF-7. Cell proliferation assays indicate that SK-OV-3 and BT 474-JB cell lines exhibit significantly reduced proliferation rates when treated with targeting-module fused dCK and fludarabine, compared to fludarabine alone. These findings demonstrate that we have succeeded in delivering active dCK into the Her2-positive cells, thereby increasing the activation of fludarabine, which ultimately reduces the dose of nucleoside analog needed for cell killing. This strategy may help establish the therapeutic index required to differentiate between healthy tissues and cancer cells. PMID- 27280470 TI - Recent Developments of Magnetic Nanoparticles for Theranostics of Brain Tumor. AB - BACKGROUND: Glioblastoma multiforme, one of the most aggressive brain tumors, has a very poor clinical outcome. Despite the introduction of the alkylating reagent temozolomide (TMZ) to surgery and radiotherapy, the survival of patients could only be modestly increased up to less than 15 months. Therefore, innovative treatment strategies are urgently needed to improve survival of glioma patients. OBJECTIVE: Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted a lot of attention due to their widespread diagnostic and therapeutic applications in neuro-oncology. In this review article we discuss the possible application of the SPIONs for the diagnostic and theraputic approaches in brain cancer. Additionally we report on recent pre-clinical and clinical developments on the generation of heat in the tumors through the application of SPIONs subjected to an alternating magnetic field (AMF). METHODS: A comprehensive review of the literature on the current status of using targeted SPIONs in brain tumor detection and therapy and also the potential hurdles to overcome was performed. RESULTS: Functionalized nanoparticles carrying tumor-specific agents, such as antibodies or proteins might further improve their tumor targeting capacity. Furthermore, multifunctional, theranostic SPIONs can be used for simultaneous in vivo tumor imaging and targeted drug deliery. Application of the ultrasound and external magnetic field technologies significantly improves accumulation of nanoparticles in brain tumors. Hyperthermic treatment using AMF has a therapeutic potential in management of brain tumors. CONCLUSION: Superparamagnetic nanoparticle-based imaging, drug delivery and hyperthermic treatment can potentially be a powerful tool for precise diagnosis and treatment of brain tumors. PMID- 27280471 TI - New parameters for childhood ventilator associated pneumonia diagnosis. AB - PURPOSE: Our aim is to determine whether the presence of soluble triggering receptor expressed on myeloid cells-1 (s-TREM-1) of bronchoalveolar lavage fluid (BALF), serum procalcitonin levels (PCT), and Clinical Pulmonary Infection Score (CPIS) have diagnostic value in children with VAP. METHODS: All children followed in pediatric intensive care unit (PICU) who were mechanically ventilated at least for 48 hr between January 2014 and December 2015 were enrolled into our study. BALF sample was obtained via non-bronchoscopic method from the children with VAP suspicion (case group) and s-TREM-1 levels were measured. Furthermore we calculated CPIS and measured serum PCT levels. Same procedures were applied to the control group who were admitted to PICU without infectious problems and who were not under antimicrobial therapy. First we compared the case group with the control group and then we compared the quantitative culture confirmed and non confirmed VAP cases among themselves. RESULTS: Case group (n:58) had significant higher PCT and s-TREM-1 levels compared to control group (n:58). The VAP confirmed cases had higher s-TREM-1, PCT ve CPIS levels compared to non-confirmed VAP cases. s-TREM-1, PCT ve CPIS variables were found to be independent risk factors for VAP. The cutoff values for s-TREM-1, CPIS, and PCT, are 281 pg/ml, 6, and 1.9 ng/ml, respectively. The patients whose s-TREM-1, CPIS, and PCT values above the cutoff levels were found to have higher cumulative VAP rate. CONCLUSIONS: s-TREM-1 of BALF, serum PCT levels, and CPIS are useful predictors for ventilator-associated pneumonia diagnosis in children. Pediatr Pulmonol. 2017;52:119-128. (c) 2016 Wiley Periodicals, Inc. PMID- 27280472 TI - Mutations Affecting Potassium Import Restore the Viability of the Escherichia coli DNA Polymerase III holD Mutant. AB - Mutants lacking the psi (HolD) subunit of the Escherichia coli DNA Polymerase III holoenzyme (Pol III HE) have poor viability, but a residual growth allows the isolation of spontaneous suppressor mutations that restore DeltaholD mutant viability. Here we describe the isolation and characterization of two suppressor mutations in the trkA and trkE genes, involved in the main E. coli potassium import system. Viability of DeltaholD trk mutants is abolished on media with low or high K+ concentrations, where alternative K+ import systems are activated, and is restored on low K+ concentrations by the inactivation of the alternative Kdp system. These findings show that the DeltaholD mutant is rescued by a decrease in K+ import. The effect of trk inactivation is additive with the previously identified DeltaholD suppressor mutation lexAind that blocks the SOS response indicating an SOS-independent mechanism of suppression. Accordingly, although lagging-strand synthesis is still perturbed in holD trkA mutants, the trkA mutation allows HolD-less Pol III HE to resist increased levels of the SOS induced bypass polymerase DinB. trk inactivation is also partially additive with an ssb gene duplication, proposed to stabilize HolD-less Pol III HE by a modification of the single-stranded DNA binding protein (SSB) binding mode. We propose that lowering the intracellular K+ concentration stabilizes HolD-less Pol III HE on DNA by increasing electrostatic interactions between Pol III HE subunits, or between Pol III and DNA, directly or through a modification of the SSB binding mode; these three modes of action are not exclusive and could be additive. To our knowledge, the holD mutant provides the first example of an essential protein-DNA interaction that strongly depends on K+ import in vivo. PMID- 27280473 TI - Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents? AB - INTRODUCTION: The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. METHODS: Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. RESULTS: OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136-11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0-16), compared with patients with OA caused by HMW agents (0.87, range 0-72), (p = 0.024). CONCLUSIONS: OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents. PMID- 27280474 TI - Youth Risk Behavior Surveillance - United States, 2015. AB - PROBLEM: Priority health-risk behaviors contribute to the leading causes of morbidity and mortality among youth and adults. Population-based data on these behaviors at the national, state, and local levels can help monitor the effectiveness of public health interventions designed to protect and promote the health of youth nationwide. REPORTING PERIOD COVERED: September 2014-December 2015. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health behaviors among youth and young adults: 1) behaviors that contribute to unintentional injuries and violence; 2) tobacco use; 3) alcohol and other drug use; 4) sexual behaviors related to unintended pregnancy and sexually transmitted infections (STIs), including human immunodeficiency virus (HIV) infection; 5) unhealthy dietary behaviors; and 6) physical inactivity. In addition, YRBSS monitors the prevalence of obesity and asthma and other priority health behaviors. YRBSS includes a national school-based Youth Risk Behavior Survey (YRBS) conducted by CDC and state and large urban school district school-based YRBSs conducted by state and local education and health agencies. This report summarizes results for 118 health behaviors plus obesity, overweight, and asthma from the 2015 national survey, 37 state surveys, and 19 large urban school district surveys conducted among students in grades 9-12. RESULTS: Results from the 2015 national YRBS indicated that many high school students are engaged in priority health-risk behaviors associated with the leading causes of death among persons aged 10-24 years in the United States. During the 30 days before the survey, 41.5% of high school students nationwide among the 61.3% who drove a car or other vehicle during the 30 days before the survey had texted or e-mailed while driving, 32.8% had drunk alcohol, and 21.7% had used marijuana. During the 12 months before the survey, 15.5% had been electronically bullied, 20.2% had been bullied on school property, and 8.6% had attempted suicide. Many high school students are engaged in sexual risk behaviors that relate to unintended pregnancies and STIs, including HIV infection. Nationwide, 41.2% of students had ever had sexual intercourse, 30.1% had had sexual intercourse during the 3 months before the survey (i.e., currently sexually active), and 11.5% had had sexual intercourse with four or more persons during their life. Among currently sexually active students, 56.9% had used a condom during their last sexual intercourse. Results from the 2015 national YRBS also indicated many high school students are engaged in behaviors associated with chronic diseases, such as cardiovascular disease, cancer, and diabetes. During the 30 days before the survey, 10.8% of high school students had smoked cigarettes and 7.3% had used smokeless tobacco. During the 7 days before the survey, 5.2% of high school students had not eaten fruit or drunk 100% fruit juices and 6.7% had not eaten vegetables. More than one third (41.7%) had played video or computer games or used a computer for something that was not school work for 3 or more hours per day on an average school day and 14.3% had not participated in at least 60 minutes of any kind of physical activity that increased their heart rate and made them breathe hard on at least 1 day during the 7 days before the survey. Further, 13.9% had obesity and 16.0% were overweight. INTERPRETATION: Many high school students engage in behaviors that place them at risk for the leading causes of morbidity and mortality. The prevalence of most health behaviors varies by sex, race/ethnicity, and grade and across states and large urban school districts. Long-term temporal changes also have occurred. Since the earliest year of data collection, the prevalence of most health-risk behaviors has decreased (e.g., riding with a driver who had been drinking alcohol, physical fighting, current cigarette use, current alcohol use, and current sexual activity), but the prevalence of other behaviors and health outcomes has not changed (e.g., suicide attempts treated by a doctor or nurse, smokeless tobacco use, having ever used marijuana, and attending physical education classes) or has increased (e.g., having not gone to school because of safety concerns, obesity, overweight, not eating vegetables, and not drinking milk). Monitoring emerging risk behaviors (e.g., texting and driving, bullying, and electronic vapor product use) is important to understand how they might vary over time. PUBLIC HEALTH ACTION: YRBSS data are used widely to compare the prevalence of health behaviors among subpopulations of students; assess trends in health behaviors over time; monitor progress toward achieving 21 national health objectives for Healthy People 2020 and one of the 26 leading health indicators; provide comparable state and large urban school district data; and help develop and evaluate school and community policies, programs, and practices designed to decrease health-risk behaviors and improve health outcomes among youth. PMID- 27280475 TI - Inhibitory effects of caffeine on gustatory plasticity in the nematode Caenorhabditis elegans. AB - The effects of caffeine on salt chemotaxis learning were investigated using the nematode Caenorhabditis elegans. To estimate the degree of salt chemotaxis learning, nematodes were placed in a mixed solution of NaCl and caffeine, and then the chemotaxis index of NaCl was obtained from the nematodes placed on agar medium after pre-exposure to caffeine concentrations of 0.01, 0.1, 0.3, and 1.0%. Locomotor activity and preference behavior for caffeine were also estimated under these caffeine conditions. Nematodes pre-exposed to 0.3% caffeine showed inhibition of salt chemotaxis learning. Additional experiments indicated that nematodes showed a preference response to the middle concentration of caffeine (0.1%), with preference behavior declining in the 0.3% caffeine condition. Stable locomotor activity was observed under 0.01-0.3% caffeine conditions. These results suggest that salt chemotaxis learning with 0.3% caffeine is useful for investigating the effects of caffeine on learning in nematodes. PMID- 27280476 TI - Two-Dimensional Magnesium Phosphate Nanosheets Form Highly Thixotropic Gels That Up-Regulate Bone Formation. AB - Hydrogels composed of two-dimensional (2D) nanomaterials have become an important alternative to replace traditional inorganic scaffolds for tissue engineering. Here, we describe a novel nanocrystalline material with 2D morphology that was synthesized by tuning the crystallization of the sodium-magnesium-phosphate system. We discovered that the sodium ion can regulate the precipitation of magnesium phosphate by interacting with the crystal's surface causing a preferential crystal growth that results in 2D morphology. The 2D nanomaterial gave rise to a physical hydrogel that presented extreme thixotropy, injectability, biocompatibility, bioresorption, and long-term stability. The nanocrystalline material was characterized in vitro and in vivo and we discovered that it presented unique biological properties. Magnesium phosphate nanosheets accelerated bone healing and osseointegration by enhancing collagen formation, osteoblasts differentiation, and osteoclasts proliferation through up-regulation of COL1A1, RunX2, ALP, OCN, and OPN. In summary, the 2D magnesium phosphate nanosheets could bring a paradigm shift in the field of minimally invasive orthopedic and craniofacial interventions because it is the only material available that can be injected through high gauge needles into bone defects in order to accelerate bone healing and osseointegration. PMID- 27280477 TI - Hypertension and Diabetic Nephropathy. PMID- 27280481 TI - Welcome letter from Jose Villadangos, President of the 16(th) International Congress of Immunology, Melbourne. PMID- 27280482 TI - TIL 2.0: More effective and predictive T-cell products by enrichment for defined antigen specificities. AB - Adoptive transfer of in vitro-expanded T cells derived from tumor-infiltrating lymphocytes (TILs) in melanoma patients started the era of tumor immunotherapy three decades ago. The approach has demonstrated remarkable clinical responses in several studies since. Reinfusion of TIL-derived T cells represents a highly personalized form of immunotherapy, taking into account the enormous interindividual tumor heterogeneity. However, despite its successes, TIL therapy does not lead to objective clinical responses in all cases. It is thus crucial to find out which tumor antigens are particularly valuable targets and to develop strategies to enhance the reactivity of T-cell products toward them. In this issue of the European Journal of Immunology, Kelderman et al. [Eur. J. Immunol. 2016. 46: 1351-1360] present a platform for the generation of antigen-specific TIL therapy. Combining recently developed technologies for clinical identification and enrichment of antigen-specific CD8(+) T cells, such as MHC Streptamers and UV-mediated peptide exchange, the authors could enrich T-cell populations with defined antigen specificities from melanoma-derived TILs. This T cell product showed higher reactivity against autologous tumor cell lines than bulk TIL-derived T cells. The novel platform might enable the generation of more effective and predictable TIL-derived T-cell products for future clinical applications. PMID- 27280485 TI - Hepatitis E virus in donor plasma collected in Japan. AB - BACKGROUND AND OBJECTIVES: Human hepatitis E virus (HEV) is prevalent worldwide. Iatrogenic HEV has recently been identified based on the reports of transfusion transmitted cases. The detection rate of HEV-RNA and seroprevalence of HEV IgG/IgM have been regionally evaluated in Japan, and donor plasma collected in Hokkaido is currently screened by nucleic acid amplification testing. However, the detection rate of HEV-RNA in blood donors in Japan outside of Hokkaido has not been reported. MATERIALS AND METHODS: A total of 620 140 qualified donor plasma samples from Japanese regions excluding Hokkaido were tested for HEV-RNA (pools of 50 or 500) between 2004 and 2014. HEV-RNA-positive plasma bags were identified, and the HEV viral load, genotype and anti-HEV immunoglobulin (Ig)G/IgM were evaluated. RESULTS: The detection rate of HEV-RNA (pools of 50) was 1/15 075 and higher in eastern than in western Japan. All 36 HEV-RNA-positive samples were genotype 3 with viral load ranging from <1.69 to 7.22 log10 copies/ml. CONCLUSIONS: Our detection rate of HEV-RNA in donor populations in Japan outside Hokkaido (1/15 075 donations) is generally lower than reported in Europe and lower than previously reported for Hokkaido (1/8173 donations). As methods varied, we cannot exclude that these differences are reflective of differing RNA detection limits. In contrast to Hokkaido where genotype 4 has been reported among blood donations, all our positive donations were genotype 3, which is less pathogenic. PMID- 27280487 TI - Alteration of classical and hematopoiesis specific p53 pathway in the bone marrow hematopoietic stem/progenitor compartment facilitates leukemia progression in experimental mice. AB - Downregulation of p53 is associated with most of the neoplasms, however it claims additional significance for hematopoietic malignancy due to its supplementary role during hematopoiesis. Apart from the classical role as tumor suppressor, p53 during steady state hematopoiesis is associated with the maintenance of quiescent cell population in bone marrow by upregulating necdin (Ndn) and Gfi-1. We felt, it is necessary to delineate its attribution towards malignant conversion of hematopoietic system during leukemogenesis from all the possible angles. The present study deals with the characterization of N-N' Ethylnitrosourea (ENU) induced mouse model of leukemia by peripheral blood hemogram, bone marrow cytology, histology, cytochemical staining (MPO) and scanning electron microscopic study. We further investigated the alteration of conventional and hematopoiesis specific p53 pathways by flowcytometric expressional analysis of ATM, Chk-2, p53, p21, Ndn, Gfi-1 and Tie-2. The disruption of classical p53 pathway was observed in leukemic hematopoietic stem/progenitor population which involved downregulation of ATM, Chk-2, p53 and p21. Moreover, the expressional decline of Ndn and Gfi-1 hinted towards the mechanism of hindrance of hematopoietic quiescency in leukemic bone marrow. Increased expression of Tie-2 due to reverse correlation with p53 was found to be responsible for pathological angiogenesis in bone marrow together with increased blast burden in bone marrow during leukemia. The study presents the mechanistic scenario of the alteration of both classical as well as hematopoiesis specific p53 pathways in HSPC compartment triggering leukemic pathophysiology. PMID- 27280488 TI - High Sensitivity, Wearable, Piezoresistive Pressure Sensors Based on Irregular Microhump Structures and Its Applications in Body Motion Sensing. AB - A pressure sensor based on irregular microhump patterns has been proposed and developed. The devices show high sensitivity and broad operating pressure regime while comparing with regular micropattern devices. Finite element analysis (FEA) is utilized to confirm the sensing mechanism and predict the performance of the pressure sensor based on the microhump structures. Silicon carbide sandpaper is employed as the mold to develop polydimethylsiloxane (PDMS) microhump patterns with various sizes. The active layer of the piezoresistive pressure sensor is developed by spin coating PEDOT: PSS on top of the patterned PDMS. The devices show an averaged sensitivity as high as 851 kPa(-1) , broad operating pressure range (20 kPa), low operating power (100 nW), and fast response speed (6.7 kHz). Owing to their flexible properties, the devices are applied to human body motion sensing and radial artery pulse. These flexible high sensitivity devices show great potential in the next generation of smart sensors for robotics, real-time health monitoring, and biomedical applications. PMID- 27280486 TI - A Method for Automated Classification of Parkinson's Disease Diagnosis Using an Ensemble Average Propagator Template Brain Map Estimated from Diffusion MRI. AB - Parkinson's disease (PD) is a common and debilitating neurodegenerative disorder that affects patients in all countries and of all nationalities. Magnetic resonance imaging (MRI) is currently one of the most widely used diagnostic imaging techniques utilized for detection of neurologic diseases. Changes in structural biomarkers will likely play an important future role in assessing progression of many neurological diseases inclusive of PD. In this paper, we derived structural biomarkers from diffusion MRI (dMRI), a structural modality that allows for non-invasive inference of neuronal fiber connectivity patterns. The structural biomarker we use is the ensemble average propagator (EAP), a probability density function fully characterizing the diffusion locally at a voxel level. To assess changes with respect to a normal anatomy, we construct an unbiased template brain map from the EAP fields of a control population. Use of an EAP captures both orientation and shape information of the diffusion process at each voxel in the dMRI data, and this feature can be a powerful representation to achieve enhanced PD brain mapping. This template brain map construction method is applicable to small animal models as well as to human brains. The differences between the control template brain map and novel patient data can then be assessed via a nonrigid warping algorithm that transforms the novel data into correspondence with the template brain map, thereby capturing the amount of elastic deformation needed to achieve this correspondence. We present the use of a manifold-valued feature called the Cauchy deformation tensor (CDT), which facilitates morphometric analysis and automated classification of a PD versus a control population. Finally, we present preliminary results of automated discrimination between a group of 22 controls and 46 PD patients using CDT. This method may be possibly applied to larger population sizes and other parkinsonian syndromes in the near future. PMID- 27280489 TI - Unusual Bandgap Oscillations in Template-Directed pi-Conjugated Porphyrin Nanotubes. AB - Using large-scale DFT calculations (up to 1476 atoms and 18 432 orbitals), we present the first detailed analysis on the unusual electronic properties of recently synthesized porphyrin nanotubes. We surprisingly observe extremely large oscillations in the bandgap of these nanostructures as a function of size, in contradiction to typical quantum confinement effects (i.e., the bandgap increases with size in several of these nanotubes). In particular, we find that these intriguing electronic oscillations arise from a size-dependent alternation of aromatic/nonaromatic characteristics in these porphyrin nanotubes. Our analyses of band structures and orbital diagrams indicate that the electronic transitions in these nanostructures are direct-bandgap, optically active "bright" states that can be readily observed in photoelectron spectroscopic experiments. Most importantly due to their unusual bandgap oscillations, we find that both type I and type II donor-acceptor p-n heterojunctions are possible in these template directed, "bottom-up synthesized" porphyrin nanotubes-a unique property that is not present in conventional carbon nanotubes. PMID- 27280490 TI - Experiments and Modeling of Boric Acid Permeation through Double-Skinned Forward Osmosis Membranes. AB - Boron removal is one of the great challenges in modern wastewater treatment, owing to the unique small size and fast diffusion rate of neutral boric acid molecules. As forward osmosis (FO) membranes with a single selective layer are insufficient to reject boron, double-skinned FO membranes with boron rejection up to 83.9% were specially designed for boron permeation studies. The superior boron rejection properties of double-skinned FO membranes were demonstrated by theoretical calculations, and verified by experiments. The double-skinned FO membrane was fabricated using a sulfonated polyphenylenesulfone (sPPSU) polymer as the hydrophilic substrate and polyamide as the selective layer material via interfacial polymerization on top and bottom surfaces. A strong agreement between experimental data and modeling results validates the membrane design and confirms the success of model prediction. The effects of key parameters on boron rejection, such as boron permeability of both selective layers and structure parameter, were also investigated in-depth with the mathematical modeling. This study may provide insights not only for boron removal from wastewater, but also open up the design of next generation FO membranes to eliminate low-rejection molecules in wider applications. PMID- 27280491 TI - Theranostic Fibers for Simultaneous Imaging and Drug Delivery. AB - New methods for creating theranostic systems with simultaneous encapsulation of therapeutic, diagnostic, and targeting agents are much sought after. This work reports for the first time the use of coaxial electrospinning to prepare such systems in the form of core-shell fibers. Eudragit S100 was used to form the shell of the fibers, while the core comprised poly(ethylene oxide) loaded with the magnetic resonance contrast agent Gd(DTPA) (Gd(III) diethylenetriaminepentaacetate hydrate) and indomethacin as a model therapeutic agent. The fibers had linear cylindrical morphologies with clear core-shell structures, as demonstrated by electron microscopy. X-ray diffraction and differential scanning calorimetry proved that both indomethacin and Gd(DTPA) were present in the fibers in the amorphous physical form. This is thought to be a result of intermolecular interactions between the different components, the presence of which was suggested by infrared spectroscopy. In vitro dissolution tests indicated that the fibers could provide targeted release of the active ingredients through a combined mechanism of erosion and diffusion. The proton relaxivities for Gd(DTPA) released from the fibers into tris buffer increased (r1 = 4.79-9.75 s(-1) mM(-1); r2 = 7.98-14.22 s(-1) mM(-1)) compared with fresh Gd(DTPA) (r1 = 4.13 s(-1) mM(-1) and r2 = 4.40 s(-1) mM(-1)), which proved that electrospinning has not diminished the contrast properties of the complex. The new systems reported herein thus offer a new platform for delivering therapeutic and imaging agents simultaneously to the colon. PMID- 27280492 TI - Leiomyomatosis Peritonealis Disseminata (LPD) ten years after laparoscopic myomectomy associated with ascites and lymph nodes enlargement: a case report. AB - INTRODUCTION: We report a case of leiomyomatosis peritonealis disseminata (LPD) arising 10 years after a laparoscopic myomectomy that was associated with ascites and lymph nodes enlargement. PRESENTATION OF CASE: The patient presented with small uterine fibroids with a dominant posterior intramural fibroid measuring 9cm in diameter and normal Doppler. Laparotomy revealed a uterus enlarged with fibroids, which was densely adhering to the urinary bladder, greater omentum, and sigmoid colon. Multiple tumors of different size were found attached to the peritoneum, omentum and bowel. The histopathologic examination was consistent with leiomyomatosis peritonealis disseminata. DISCUSSION: Pieces of smooth muscle cell lost in the abdominal cavity during electrical morcellation after laparoscopic myomectomy may progress to leiomyomatosis peritonealis disseminata even after many years (ten in our case) and it can be associated with ascites and lymph nodes enlargement. CONCLUSION: This is the first case reported in literature of leiomyomatosis peritonealis disseminata with these particular features (time of clinical presentation, ascites, lymph nodes enlargement). PMID- 27280493 TI - Self-Arranged Misfit Dislocation Network Formation upon Strain Release in La0.7Sr0.3MnO3/LaAlO3(100) Epitaxial Films under Compressive Strain. AB - Lattice-mismatched epitaxial films of La0.7Sr0.3MnO3 (LSMO) on LaAlO3 (001) substrates develop a crossed pattern of misfit dislocations above a critical thickness of 2.5 nm. Upon film thickness increases, the dislocation density progressively increases, and the dislocation spacing distribution becomes narrower. At a film thickness of 7.0 nm, the misfit dislocation density is close to the saturation for full relaxation. The misfit dislocation arrangement produces a 2D lateral periodic structure modulation (Lambda ~ 16 nm) alternating two differentiated phases: one phase fully coherent with the substrate and a fully relaxed phase. This modulation is confined to the interface region between film and substrate. This phase separation is clearly identified by X-ray diffraction and further proven in the macroscopic resistivity measurements as a combination of two transition temperatures (with low and high Tc). Films thicker than 7.0 nm show progressive relaxation, and their macroscopic resistivity becomes similar than that of the bulk material. Therefore, this study identifies the growth conditions and thickness ranges that facilitate the formation of laterally modulated nanocomposites with functional properties notably different from those of fully coherent or fully relaxed material. PMID- 27280494 TI - Small RNAs Play Big Roles: MicroRNAs in Diabetic Wound Healing. AB - Skin and corneal wounds in diabetics are a major healthcare burden. MicroRNAs are small, non-coding RNAs that post-transcriptionally regulate the expression of protein-coding genes. Studies have identified microRNAs involved in all phases of wound healing. The dysregulation of microRNAs can contribute to impaired or delayed skin and corneal wound healing in diabetics. Here, we present a comprehensive review of the literature involving microRNAs in diabetic skin and corneal wound healing as well as those serving as potential biomarkers for diabetic wound healing. PMID- 27280495 TI - Subpopulations of Bone Marrow Mesenchymal Stem Cells Exhibit Differential Effects in Delaying Retinal Degeneration. AB - Bone marrow mesenchymal stem cells (BMSCs) have a therapeutic role in retinal degeneration (RD). However, heterogeneity of BMSCs may be associated with differential therapeutic effects in RD. In order to confirm this hypothesis, two subsets of rat BMSCs, termed rBMSC1 and rBMSC2, were obtained, characterized and functionally evaluated in the treatment of RD of Royal College of Surgeons (RCS) rats. Both subpopulations expressed mesenchymal stem cells (MSC) markers CD29 and CD90, but were negative for hemacyte antigen CD11b and CD45 expression. In comparison with rBMSC2, rBMSC1 showed higher rate of proliferation, stronger colony formation, and increased adipogenic potential, whereas rBMSC2 exhibited higher osteogenic potential. Microarray analysis showed differential gene expression patterns between rBMSC1 and rBMSC2, including functions related to proliferation, differentiation, immunoregulation, stem cell maintenance and division, survival and antiapoptosis. After subretinal transplantation in RCS rats, rBMSC1 showed stronger rescue effect than rBMSC2, including increased b wave amplitude, restored retinal nuclear layer thickness, and decreased number of apoptotic photoreceptors, whereas the rescue function of rBMSC2 was essentially not better than the control. Histological analysis also demonstrated that rBMSC1 possessed a higher survival rate than rBMSC2 in subretinal space. In addition, treatment of basic fibroblast growth factor, an accompanying event in subretinal injection, triggered more robust increase in secretion of growth factors by rBMSC1 as compared to rBMSC2. Taken together, these results have suggested that the different therapeutic functions of BMSC subpopulations are attributed to their distinct survival capabilities and paracrine functions. The underlying mechanisms responsible for the different functions of BMSC subpopulation may lead to a new strategy for the treatment of RD. PMID- 27280496 TI - Human Adipose-Derived Stem Cells Delay Retinal Degeneration in Royal College of Surgeons Rats Through Anti-Apoptotic and VEGF-Mediated Neuroprotective Effects. AB - Stem cell therapy is a promising therapeutic approach for retinal degeneration (RD). Our study investigated the effects of human adipose derived stem cell (hADSCs) on Royal College of Surgeons (RCS) rats. METHODS: Green fluorescent protein (GFP)-labeled hADSCs were transplanted subretinally into RCS rats at postnatal (PN) 21 days to explore potential therapeutic effects, while adeno associated viral vector (AAV2)-vascular endothelial growth factor (VEGF) and siVEGF-hADSCs were used to aid the mechanistic dissections. Visual function was evaluated by Electroretinogram (ERG) recording. Potential transdifferentiations were examined by Immunofluorescence (IF) and gene expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Apoptotic retinal cells were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) assay and the cytokines secreted by hADSCs were measured by Enzyme-linked Immunosorbent Assay (ELISA). RESULTS: The visual function of RCS rats began to decrease one week after their eyes opened at PN week 3 and almost lost in PN 5 weeks, accompanied by the loss of retinal outer nuclear layer (ONL). Subretinal transplantation of hADSCs significantly improved the visual function 2 weeks after the transplantation and such therapeutic effect persisted up to 8 weeks after the treatment (PN 11 weeks), with 3-4 rows of photoreceptors remained in the ONL and reduced apoptosis. Consistent with these phenotypic changes, the gene expression of rod photoreceptor markers Rhodopsin (Rho), Crx and Opsin (Opn1) in RCS rats showed obvious decreasing trends over time after PN 3 weeks, but were elevated with hADSC treatment. hADSC transplantation also repressed the expressions of Bax, Bak and Caspase 3, but not the expression of anti-apoptotic genes, including Bcl-2 and Bcl-XL. Finally, substantial VEGF, hepatocyte growth factor (HGF) and pigment epithelium-derived factor (PEDF) secretions from hADSCs were detected, while endogenous Vegf expression level decreased over time in RCS rats. The treatment of AAV2-VEGF showed comparable therapeutic effects as hADSCs but siRNA knockdown of VEGF in hADSCs essentially abolished the therapeutic effects. CONCLUSIONS: Subretinal transplantation of hADSCs in RCS rats effectively delayed the retinal degeneration, enhanced the retinal cell survival and improved the visual function. Mechanistically this was mainly due to hADSC dependent anti-apoptotic and neuroprotective effects through its secretion of growth and neurotrophic factors including VEGF. Clinical application of hADSCs merits further investigation. PMID- 27280498 TI - Prostate-Specific G-Protein Coupled Receptor, an Emerging Biomarker Regulating Inflammation and Prostate Cancer Invasion. AB - Prostate cancer is highly prevalent among men in developed countries, but a significant proportion of detected cancers remain indolent, never progressing into aggressive carcinomas. This highlights the need to develop refined biomarkers that can distinguish between indolent and potentially dangerous cases. The prostate-specific G-protein coupled receptor (PSGR, or OR51E2) is an olfactory receptor family member with highly specific expression in human prostate epithelium that is highly overexpressed in PIN and prostate cancer. PSGR has been functionally implicated in prostate cancer cell invasiveness, suggesting a potential role in the transition to metastatic PCa. Recently, transgenic mice overexpressing PSGR in the prostate were reported to develop an acute inflammatory response followed by emergence of low grade PIN, whereas mice with compound PSGR overexpression and loss of PTEN exhibited accelerated formation of invasive prostate adenocarcinoma. This article will review recent PSGR findings with a focus on its role as a potential prostate cancer biomarker and regulator of prostate cancer invasion and inflammation. PMID- 27280497 TI - LASS5 Interacts with SDHB and Synergistically Represses p53 and p21 Activity. AB - Longevity Assurance 5 (LASS5), a member of the LASS/Ceramide Synthases family, synthesizes C16-ceramide and is implicated in tumor biology. However, its precise role is not yet well understood. A yeast two-hybrid screen was performed using a human cDNA library to identify potential LASS5- interaction partners. One identified clone encodes succinate dehydrogenase subunit B (SDHB). Mammalian two hybrid assays showed that LASS5 interacts with SDHB, and the result was also confirmed by GST pull-down and coimmunoprecipitation assays. The C-terminal fragment of SDHB was required for the interaction. LASS5 and SDHB were co localized in COS-7 cells. LASS5 and SDHB expressions were found to be up regulated in neuroglioma tissue. Transfection assays showed that LASS5 or SDHB expression repressed p53 or p21 reporter activity, respectively. Simultaneous LASS5 and SDHB expression resulted in stronger repression of p53 and p21 reporter activity, suggesting that LASS5 and SDHB interaction may synergistically affect transcriptional regulation of p53 and p21. Our data provide new molecular insights into potential roles of LASS5 and SDHB in tumor biology. PMID- 27280499 TI - Design, Synthesis, and In Vitro and In Vivo Evaluation of an (18)F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer. AB - Sphingosine 1-phosphate receptor 1 (S1P1) plays a pivotal signaling role in inflammatory response; because S1P1 modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P1 would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P1 (S1P1 IC50 < 10 nM, >100-fold selectivity for S1P1 over S1P2 and S1P3). The most potent ligand, 28c (IC50 = 2.63 nM for S1P1) was (18)F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P1-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [(18)F]28c accumulation in the liver of LPS treated mice than controls. Increased expression of S1P1 in the LPS model was confirmed by immunohistochemical analysis (IHC). These data suggest that [(18)F]28c is a S1P1 PET tracer with high potential for imaging S1P1 in vivo. PMID- 27280500 TI - Amelioration of Clostridium difficile Infection in Mice by Dietary Supplementation With Indole-3-carbinol. AB - OBJECTIVE: To determine the therapeutic effects of dietary supplementation on Clostridium difficile infection (CDI). BACKGROUND: With limited treatment options, the rise of C. difficile-associated disease has spurred on the search for novel therapies. Recent data define a role for the aryl hydrocarbon receptor (AHR) and diet-derived AHR ligands in mucosal immunity. We investigated the efficacy of indole-3-carbinol (I3C), a dietary supplement, and AHR precursor ligand in a murine model of CDI. METHODS: C57BL/6 (B6), AHR, and AHR mice were placed on either grain-based or semipurified diets with or without I3C before and during CDI. Mice were followed clinically for a minimum of 6 days or euthanized between days 0 and 4 of inoculation for analysis of the inflammatory response and microbiota. RESULTS: B6 mice fed an AHR ligand-deficient, semipurified diet have significantly increased disease severity (P<0.001) and mortality (P < 0.001) compared with mice fed on diet containing I3C. The addition of I3C to the diet of AHR null mice had less of an impact than in AHR heterozygous littermates, although some protection was seen. Mice on semipurified I3C-diet had increased cecal Tregs, ILC3s, and gammadelta T cells and an increased neutrophilic response without increased inflammation or bacterial translocation compared with controls. CONCLUSIONS: I3C is a powerful treatment to reduce impact of CDI in mice. The findings indicate I3C may be acting through both AHR-dependent and -independent mechanisms in this model. Dietary supplementation with I3C is a potential new therapy for prevention and amelioration of C. difficile disease. PMID- 27280501 TI - Three-year Results of a Pilot Program in Early Liver Transplantation for Severe Alcoholic Hepatitis. AB - OBJECTIVE: To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in October 2012. BACKGROUND: Six months of alcohol abstinence is typically required before liver transplant. A Franco-Belgian protocol showed that early transplant in severe alcoholic hepatitis could improve survival with low incidence of alcohol relapse. Application of this controversial indication is growing despite unclear generalizability. METHODS: Data was collected on all patients with alcohol-related liver disease since initiation of the pilot through June 2015. Patients were stratified into two groups: severe alcoholic hepatitis as first liver decompensation (Group 1), alcoholic cirrhosis with >=6 months abstinence (Group 2). Alcohol relapse was defined as any evidence of alcohol consumption after transplant, which was assessed for harmful patterns of binge or frequent drinking. RESULTS: Forty-three patients underwent liver transplant, including 17 patients in Group 1. Six-month survival was 100% versus 89% for Groups 1 and 2, respectively (P = 0.27). Alcohol relapse was similar in Group 1 versus Group 2: 23.5% versus 29.2% (P > 0.99). Harmful drinking was higher in Group 1 versus Group 2, despite lack of statistical significance: 23.5% versus 11.5% (P = 0.42). CONCLUSIONS: In this pilot with carefully selected patients, early liver transplant provided excellent short-term survival, and similar rates of alcohol relapse compared with patients with 6 months of abstinence. Harmful patterns of relapse remain challenging in this population, highlighting the need for validated models to predict alcohol relapse, and need for extreme caution in selecting patients for this exceptional indication. Larger prospective studies and longer follow up are necessary. PMID- 27280502 TI - Multicenter, Prospective Trial of Selective Drain Management for Pancreatoduodenectomy Using Risk Stratification. AB - OBJECTIVE: This multicenter study sought to prospectively evaluate a drain management protocol for pancreatoduodenectomy (PD). BACKGROUND: Recent evidence suggests value for both selective drain placement and early drain removal for PD. Both strategies have been associated with reduced rates of clinically relevant pancreatic fistula (CR-POPF)-the most common and morbid complication after PD. METHODS: The protocol was applied to 260 consecutive PDs performed at two institutions over 17 months. Risk for ISGPF CR-POPF was determined intraoperatively using the Fistula Risk Score (FRS); drains were omitted in negligible/low risk patients and drain fluid amylase (DFA) was measured on postoperative day 1 (POD 1) for moderate/high risk patients. Drains were removed early (POD 3) in patients with POD 1 DFA <=5,000 U/L, whereas patients with POD 1 DFA >5,000 U/L were managed by clinical discretion. Outcomes were compared with a historical cohort (N = 557; 2011-2014). RESULTS: Fistula risk did not differ between cohorts (median FRS: 4 vs 4; P = 0.933). No CR-POPFs developed in the 70 (26.9%) negligible/low risk patients. Overall CR-POPF rates were significantly lower after protocol implementation (11.2 vs 20.6%, P = 0.001). The protocol cohort also demonstrated lower rates of severe complication, any complication, reoperation, and percutaneous drainage (all P < 0.05). These patients also experienced reduced hospital stay (median: 8 days vs 9 days, P = 0.001). There were no differences between cohorts in the frequency of bile or chyle leaks. CONCLUSIONS: Drains can be safely omitted for one-quarter of PDs. Drain amylase analysis identifies which moderate/high risk patients benefit from early drain removal. This data-driven, risk-stratified approach significantly decreases the occurrence of clinically relevant pancreatic fistula. PMID- 27280503 TI - The Hidden Consequences of the Volume Pledge: "No Patient Left Behind"? PMID- 27280504 TI - The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma. AB - OBJECTIVE: The objective of this study was to analyze the impact on overall survival (OS) from the addition of postoperative radiation with or without chemotherapy after esophagectomy, using a large, hospital-based dataset. BACKGROUND: Previous retrospective studies have suggested an OS advantage for postoperative chemoradiation over surgery alone, although prospective data are lacking. METHODS: The National Cancer Data Base was queried to select patients diagnosed with stage pT3-4Nx-0M0 or pT1-4N1-3M0 esophageal carcinoma (squamous cell or adenocarcinoma) from 1998 to 2011 treated with definitive esophagectomy +/- postoperative radiation and/or chemotherapy. OS was analyzed using the Kaplan Meier method and compared using the log-rank test. Multivariate Cox regression analysis was used to identify covariates associated with OS. RESULTS: There were 4893 patients selected, of whom 1153 (23.6%) received postoperative radiation. Most patients receiving radiation also received sequential/concomitant chemotherapy (89.9%). For the entire cohort, postoperative radiation was associated with a statistically significant but modest absolute improvement in survival (hazard ratio 0.77; 95% CI, 0.71-0.83; P < 0.001). On subgroup analysis, postoperative radiation was associated with improved OS for patients with node positive disease (3-yr OS 34.3 % vs 27.8%, P < 0.001) or positive margins (3-yr OS 36.4% vs 18.0%, P < 0.001). When chemotherapy usage was incorporated, sequential chemotherapy was associated with the best survival (P < 0.001). Multivariate analysis revealed that the addition of chemotherapy to radiation therapy, whether sequentially or concurrently, was a strong prognostic factor for OS. CONCLUSIONS: In this hospital-based study, the addition of postoperative chemoradiation (either sequentially or concomitantly) after esophagectomy was associated with improved OS for patients with node-positive disease or positive margins. PMID- 27280505 TI - Abdominal Wall Reconstruction for Incisional Hernia Optimizes Truncal Function and Quality of Life: A Prospective Controlled Study. AB - OBJECTIVE: The aim of the study was to examine abdominal wall function in patients undergoing abdominal wall reconstruction (AWR) for incisional hernia. BACKGROUND: The literature on abdominal wall function in patients with incisional hernia is sparse. It has been suggested that AWR leads to improvement in function, but it is unknown whether this is specific to the abdominal wall or due to an improvement in overall physical fitness. METHODS: We performed a prospective case-control study of 18 consecutive patients with large incisional hernia undergoing AWR with linea alba restoration. Truncal flexion and extension strength, hand grip strength, leg extension power, and quality of life (SF-36 and Carolinas Comfort Scale) were assessed preoperatively and 1 year postoperatively. Patients were compared with a control group of patients with an intact abdominal wall undergoing colorectal resection (n = 18). The study was registered at ClinicalTrials.gov (NCT02011048). RESULTS: Compared with preoperative measurements, 1-year follow-up after AWR demonstrated an increase of both truncal flexion strength (from mean 505.6 N to 572.3 N, P < 0.001) and truncal extension strength (from 556.7 to 606.0 N, P = 0.005). There was no significant change of either hand grip strength or leg extension power. After AWR, the physical component of overall quality of life improved, whereas the mental component score remained unchanged. In the control group, surgery resulted in a decrease in both truncal flexion and truncal extension. CONCLUSIONS: AWR for incisional hernia specifically improved long-term abdominal wall muscular function and quality of life. PMID- 27280507 TI - How Far Are Patients Willing to Travel for Gastrectomy? AB - OBJECTIVE: To determine travel patterns for patients undergoing gastrectomy for cancer and to identify factors associated with patient decision. BACKGROUND: Support for regionalization of complex surgery grows; however, little is known about the willingness of patients to travel for care. Furthermore, utilization of outcomes data in patients' hospital selection processes is not well understood. METHODS: Analysis of the California Office of Statewide Health Planning and Development database from 1996 to 2009. Outcome measures included total distance traveled and rate of bypassing the nearest gastrectomy-performing hospitals. Multivariate analyses to identify predictors of bypassing local hospitals were performed. RESULTS: Total study population was 10,022. Majority (67.1%) of patients underwent gastrectomy at the nearest providing hospitals. Distance traveled to destination hospitals in California averaged 17.04 miles. Bypassing patients traveled approximately 16 miles beyond the nearest hospitals to receive care, selecting lower volume destination hospitals in 27.9% of cases. Annual gastrectomy volumes for nearest and for destination hospitals averaged 4.4 and 6.8 cases, respectively, and inhospital mortality rates were 5.9% and 4.8%, respectively. A few patients (19.2%) sought care at teaching hospitals. Rural county residence significantly reduced the likelihood of bypass (P < 0.001). High volume (>7 cases) and teaching status of destination hospitals (both P < 0.001) were predictive of hospital bypass, though no significant association between mortality rate and bypass was identified. CONCLUSIONS: The majority of gastric cancer patients underwent gastrectomy at providing hospitals nearest to home, reflecting little regionalization of gastrectomy in California. Patients' hospital selection appears not to be driven by outcomes data. PMID- 27280506 TI - Trauma Recidivism Predicts Long-term Mortality: Missed Opportunities for Prevention (Retrospective Cohort Study). AB - OBJECTIVES: The objectives of this study were to determine the association between recurrent trauma admissions (recidivism) and subsequent long-term mortality, and to identify those in most need for preventive interventions. BACKGROUND: Patients with a single intentional injury have been shown to have a higher risk of future injury mortality than those with unintentional injury with 5-year mortality rates as high as 20% being reported for recurrent penetrating trauma. Trauma recidivism identifies a high-risk population, but its association with long-term mortality is largely unknown. METHODS: Patients with 1 or more previous admissions to an urban trauma center (recidivists) were identified and compared with those with single admissions (nonrecidivists) from 1997 to 2008. The trauma registry was linked to the National Death Index to determine both the cause and time to death after hospital discharge. Statistical analysis included chi-square tests, Kaplan-Meier survival curves, and Cox proportional-hazards models. RESULTS: Trauma recidivists were 7% of the total trauma population from 1997 to 2008, representing 3147 patients. Recidivists were more likely to be male (P < 0.0001), Black (P < 0.0001), have a blood alcohol content above 80 mg/dL (P < 0.0001), and suffer a penetrating injury (P < 0.0001) compared with nonrecidivists. Recidivists with both initial blunt and penetrating injuries had higher rates of long-term mortality after discharge. Recidivists were more likely to die of any cause based on Cox proportional-hazard ratios [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.57-2.01], injury death (HR 2.02, 95% CI 1.66 2.47), and disease death (HR 1.65, 95% CI 1.41-1.92) than nonrecidivists. CONCLUSIONS: Male sex, Black race, and elevated blood alcohol content and penetrating injury are associated with trauma recidivism which leads to a higher risk of death. There is a critical public health need to develop interventions to reduce trauma recidivism and preventable death. PMID- 27280508 TI - Randomized Controlled Trial of the Intraportal Chemotherapy Combined With Adjuvant Chemotherapy (mFOLFOX6) for Stage II and III Colon Cancer. PMID- 27280509 TI - Prognostic Impact of Postoperative Morbidity After Esophagectomy for Esophageal Cancer: Exploratory Analysis of JCOG9907. AB - OBJECTIVE: To investigate the influence of infectious complications on the outcome of current standard preoperative chemotherapy followed by surgery for clinical stage II/III esophageal cancer. BACKGROUND: The impact of postoperative infectious complications on survival after transthoracic esophagectomy remains controversial. METHODS: Data from a randomized controlled trial (JCOG9907) were used. Infectious complications were classified into three groups: pneumonia, anastomotic leakage, and others. Univariate and multivariate analyses using the Cox proportional hazard model were performed. RESULTS: Among the 152 analyzed patients, the incidence of pneumonia, leakage, and overall infectious complication were 22 (14%), 21 (14%), and 54 (36%). Overall survival (OS) of patients with any infectious complication was shorter than that of patients without infectious complication [hazard ratio, HR 1.66, 95% confidence interval, CI, (1.02-2.71)] and progression-free survival (PFS) also tended to be shorter in patients with any infectious complication [HR 1.44, (0.92-2.24)]. The OS of patients with pneumonia was shorter than that of patients without pneumonia [HR 1.82, (1.01-3.29)], and PFS also tended to be shorter in patients with pneumonia [HR 1.50, (0.85-2.62)]. The OS of patients with anastomotic leakage (n = 21) was nearly identical to that for patients without leakage [HR 1.06, (0.52-2.13)] and PFS showed the same tendency [HR 1.28, (0.71-2.32)]. Multivariate analysis revealed that pneumonia tended to compromise OS and PFS [HR 1.66, (0.87-3.17) and HR 1.37, (0.75-2.51)]. CONCLUSIONS: These results indicate that postoperative infectious complications may worsen patient prognosis after esophagectomy. Performing esophagectomy without postoperative complications, especially pneumonia, may be beneficial for improving survival outcomes. PMID- 27280510 TI - The "Ultimate Jazz": Finding the Silver Lining Among Clinical Experience, Guidelines, and Legislation. PMID- 27280511 TI - Randomized Controlled Trial to Evaluate Splenectomy in Total Gastrectomy for Proximal Gastric Carcinoma. AB - OBJECTIVE: To clarify the role of splenectomy in total gastrectomy for proximal gastric cancer. BACKGROUNDS: Splenectomy in total gastrectomy is associated with increased operative morbidity and mortality, but its survival benefit is unclear. Previous randomized controlled trials were underpowered and inconclusive. METHODS: We conducted a multiinstitutional randomized controlled trial. Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During the operation, surgeons confirmed that R0 resection was possible with negative lavage cytology, and patients were randomly assigned to either splenectomy or spleen preservation. The primary endpoint was overall survival (OS) and the secondary endpoints were relapse-free survival, operative morbidity, operation time, and blood loss. The trial was designed to confirm noninferiority of spleen preservation to splenectomy in OS with a noninferiority margin of the hazard ratio as 1.21 and 1-sided alpha of 5%. RESULTS: Between June 2002 and March 2009, 505 patients (254 splenectomy, 251 spleen preservation) were enrolled from 36 institutions. Splenectomy was associated with higher morbidity and larger blood loss, but the operation time was similar. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen preservation groups, respectively. The hazard ratio was 0.88 (90.7%, confidence interval 0.67-1.16) (<1.21); thus, the noninferiority of spleen preservation was confirmed (P = 0.025). CONCLUSIONS: In total gastrectomy for proximal gastric cancer that does not invade the greater curvature, splenectomy should be avoided as it increases operative morbidity without improving survival. PMID- 27280512 TI - Impact of Intraoperative Re-resection to Achieve R0 Status on Survival in Patients With Pancreatic Cancer: A Single-center Experience With 483 Patients. AB - OBJECTIVE: The aim of this study was to test the hypothesis that intraoperative frozen section (FS) and re-resection results to achieve R0 status are associated with different long-term outcomes in pancreatic cancer patients. BACKGROUND: Recent data have challenged the survival benefit of additional resection in patients with pancreatic cancer in case of positive FS to achieve clear pathological section (PS). METHODS: Patients who underwent surgery for exocrine pancreatic malignancy with curative intent were identified from a prospective database. Data were stratified by resection margin (group I: FS-R0 -> PS-R0; group II: FS-R1 -> PS-R0; group III: FS-R1 -> PS-R1). Associations with survival were analyzed by univariate and multivariate analyses. RESULTS: A total of 483 patients met the inclusion criteria. Of these, 61 patients were excluded due to R2 or Rx status. Three hundred seventeen (75%) patients were allocated to margin group I, 32 (8%) to group II, and 73 (17%) to group III. Median overall survival in group I, II, and III was 29, 36, and 12 months (P < 0.001). There was no significant difference in survival between patients in Group I and II (P = 0.849), whereas patients in group III had significantly poorer outcome than group I (P < 0.001) and II (P = 0.039). The prognostic value of margin group status was confirmed on multivariate analysis (hazard ratio = 1.694, 95% confidence interval 1.175-2.442). CONCLUSIONS: FS analysis with intraoperative re-resection should be performed routinely in patients undergoing pancreatic cancer surgery with the aim to achieve a R0 resection. PMID- 27280513 TI - Reply to Letter: Alvimopan Is Associated With Improved Outcomes and Cost Savings in Enhanced Recovery Colorectal Surgery Protocols. PMID- 27280514 TI - Future Supply of Pediatric Surgeons: Analytical Study of the Current and Projected Supply of Pediatric Surgeons in the Context of a Rapidly Changing Process for Specialty and Subspecialty Training. AB - OBJECTIVE: To describe the future supply and demand for pediatric surgeons using a physician supply model to determine what the future supply of pediatric surgeons will be over the next decade and a half and to compare that projected supply with potential indicators of demand and the growth of other subspecialties. BACKGROUND: Anticipating the supply of physicians and surgeons in the future has met with varying levels of success. However, there remains a need to anticipate supply given the rapid growth of specialty and subspecialty fellowships. This analysis is intended to support decision making on the size of future fellowships in pediatric surgery. METHODS: The model used in the study is an adaptation of the FutureDocs physician supply and need tool developed to anticipate future supply and need for all physician specialties. Data from national inventories of physicians by specialty, age, sex, activity, and location are combined with data from residency and fellowship programs and accrediting bodies in an agent-based or microsimulation projection model that considers movement into and among specialties. Exits from practice and the geographic distribution of physician and the patient population are also included in the model. Three scenarios for the annual entry into pediatric surgery fellowships (28, 34, and 56) are modeled and their effects on supply through 2030 are presented. RESULTS: The FutureDocs model predicts a very rapid growth of the supply of surgeons who treat pediatric patients-including general pediatric surgeon and focused subspecialties. The supply of all pediatric surgeons will grow relatively rapidly through 2030 under current conditions. That growth is much faster than the rate of growth of the pediatric population. The volume of complex surgical cases will likely match this population growth rate meaning there will be many more surgeons trained for those procedures. The current entry rate into pediatric surgery fellowships (34 per year) will result in a slowing of growth after 2025, a rate of 56 will generate a continued growth through 2030 with a likely plateau after 2035. CONCLUSIONS: The rate of entry into pediatric surgery will continue to exceed population growth through 2030 under two likely scenarios. The very rapid anticipated growth in focused pediatric subspecialties will likely prove challenging to surgeons wishing to maintain their skills with complex cases as a larger and more diverse group of surgeons will also seek to care for many of the conditions and patients which the general pediatric surgeons and general surgeons now see. This means controlling the numbers of pediatric surgery fellowships in a way that recognizes problems with distribution, the volume of cases available to maintain proficiency, and the dynamics of retirement and shifts into other specialty practice. PMID- 27280515 TI - Surgical Outcomes for Mastectomy Patients Receiving Neoadjuvant Chemotherapy: A Propensity-Matched Analysis. AB - OBJECTIVE: To evaluate the risk of neoadjuvant chemotherapy for surgical morbidity after mastectomy with or without reconstruction using 1:1 matching. BACKGROUND: Postoperative surgical complications remain a potentially preventable event for breast cancer patients undergoing mastectomy. Neoadjuvant chemotherapy is among variables identified as contributory to risk, but it has not been rigorously evaluated as a principal causal influence. METHODS: Data from American College of Surgeons National Surgical Quality Improvement Program (2006-2012) were used to identify females with invasive breast cancer undergoing planned mastectomy. Surgical cases categorized as clean and undergoing no secondary procedures unrelated to mastectomy were included. A 1:1 matched propensity analysis was performed using neoadjuvant chemotherapy within 30 days of surgery as treatment. A total of 12 preoperative variables were used with additional procedure matching: bilateral mastectomy, nodal surgery, tissue, and/or implant. Outcomes examined were 4 wound occurrences, sepsis, and unplanned return to the operating room. RESULTS: We identified 31,130 patient procedures with 2488 (7.5%) receiving chemotherapy. We matched 2411 cases, with probability of treatment being 0.005 to 0.470 in both cohorts. Superficial wound complication was the most common wound event, 2.24% in neoadjuvant-treated versus 2.45% in those that were not (P = 0.627). The rate of return to the operating room was 5.7% in the neoadjuvant group versus 5.2% in those that were not (P = 0.445). The rate of sepsis was 0.37% in the neoadjuvant group versus 0.46% in those that were not (P = 0.654). CONCLUSIONS: This large, matched cohort study, controlled for preoperative risk factors and most importantly for the surgical procedure performed, demonstrates that breast cancer patients receiving neoadjuvant chemotherapy have no increased risk for surgical morbidity. PMID- 27280516 TI - Mastery of Care-toward Communitarian Regulation. PMID- 27280517 TI - Adhesion Prevention: Safety Before Cost. PMID- 27280518 TI - Along Came the Patient (Evidence Killed the Surgical Star). PMID- 27280519 TI - Phase-Variance Optical Coherence Tomographic Angiography Imaging of Choroidal Perfusion Changes Associated With Acute Posterior Multifocal Placoid Pigment Epitheliopathy. PMID- 27280520 TI - Emergency Preparedness and Role Clarity among Rescue Workers during the Terror Attacks in Norway July 22, 2011. AB - BACKGROUND: Few studies address preparedness and role clarity in rescue workers after a disaster. On July 22, 2011, Norway was struck by two terror attacks; 77 people were killed and many injured. Healthcare providers, police officers and firefighters worked under demanding conditions. The aims of this study were to examine the level of preparedness, exposure and role clarity. In addition, the relationship between demographic variables, preparedness and exposure and a) role clarity during the rescue operations and; b) achieved mastering for future disaster operations. METHODS: In this cross-sectional study, healthcare providers (n = 859), police officers (n = 252) and firefighters (n = 102) returned a questionnaire approximately 10 months after the terror attacks. RESULTS: The rescue personnel were trained and experienced, and the majority knew their professional role (healthcare providers M = 4.1 vs. police officers: M = 3.9 vs. firefighters: M = 4.2, p < .001, [scale 1-5]). The police officers reported significantly more lack of control (p < .001). In the multivariable analysis, being female (OR 1.4, p < .05), having more years of work experience (OR 2.3, p = < .001), previous training (OR 1.6, p < .05) and the experience of an event with > 5 fatalities (OR 1.6, p < .05) were all associated with role clarity, together with a feeling of control, not being obstructed in work and perceiving the rescue work as a success. Moreover, independent predictors of being more prepared for future operations were arousal during the operation (OR 2.0, p < .001) and perceiving the rescue work as a success (OR 1.5, p < .001). CONCLUSION: Most of the rescue workers were experienced and knew their professional role. Training and everyday-work-experience must be a focal point when preparing rescue workers for disaster. PMID- 27280521 TI - Parenting stress among parents of children with Neurodevelopmental Disorders. AB - In recent years, studies have shown that parents of children with Neurodevelopmental Disorders (NDDs) experience more parenting stress than parents of typically developing children, but the relation between the type of disorders and parenting stress is far from clear. The purpose of this study was to compare the parenting stress experienced by parents of 239 children with Specific Learning Disorders (SpLD), Language Disorders (LD), Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), and typical development (TD). Parents of children with NDDs experience more parenting stress than those of children who have TD. Although, parents of children with ASD or ADHD report the most high scores of parenting stress, also the parents of children with SpLD or LD report higher parental stress compared with parent of children without NDDs. Another interesting finding was that IQ level or emotional and behavioral problems are associated with the higher levels of parenting stress. This study suggest that parent, both mothers and fathers, of children with different type of NDDs should be provided with interventions and resources to empower them with the knowledge and skills to reduce their stress and to enhance their quality of life. PMID- 27280523 TI - Efficacy and feasibility of the Integrated Psychological Therapy for outpatients with schizophrenia in Greece: Final results of a RCT. AB - The goal of this study was to evaluate the efficacy and the feasibility of cognitive remediation group therapy in patients with schizophrenia in Greece. For this purpose, the cognitive part of the Integrated Psychological Therapy (IPT), focusing on neuro- and social cognition, was compared in a randomized controlled trial (RCT) with treatment as usual (TAU). 48 outpatients took part in the study. IPT groups received 20 biweekly 1-h-therapy sessions. A test-battery was assessed at baseline, after therapy, and at a 3-month follow-up. Regarding cognitive functioning, significant effects favouring IPT were found in working memory and social perception during therapy and at follow-up. No effects could be found in verbal memory and vigilance. Significant effects favoring IPT were found in negative symptoms, in insight and in general symptoms during therapy and at follow-up using the Positive and Negative Syndrome Scale (PANSS). No effects were evident in positive symptoms and in psychosocial functioning. Significant effects favoring TAU were found in the quality of life assessment at follow-up. The study supports evidence for the feasibility and efficacy of IPT in psychiatric care in Greece and it hopefully will initiate the broader use of evidenced-based treatments like IPT in Greek Psychiatry. PMID- 27280522 TI - Cortisol levels at baseline and under stress in adolescent males with attention deficit hyperactivity disorder, with or without comorbid conduct disorder. AB - Reported findings on cortisol reactivity to stress in young people with ADHD are very variable. This inconsistency may be explained by high rates of comorbidity with Conduct Disorder (CD). The present study examined cortisol responses to a psychosocial stressor in a large sample of adolescent males with ADHD (n=202), with or without a comorbid diagnosis of Conduct Disorder (CD). Associations between stress reactivity and callous-unemotional traits and internalizing symptoms were also assessed. The ADHD only (n=95) and ADHD+CD (n=107) groups did not differ in baseline cortisol, but the ADHD+CD group showed significantly reduced cortisol stress reactivity relative to the ADHD only group. Regression analyses indicated that ADHD symptom severity predicted reduced baseline cortisol, whereas CD symptom severity predicted increased baseline cortisol (ADHD beta=-0.24, CD beta=0.16, R=0.26) and reduced cortisol stress reactivity (beta= 0.17, R=0.17). Callous-unemotional traits and internalizing symptoms were not significantly related to baseline or stress-induced cortisol. Impaired cortisol reactivity is hypothesised to reflect fearlessness and is associated with deficient emotion regulation and inhibition of aggressive and antisocial behaviour. Consequently, it may partly explain the greater severity of problems seen in those with comorbid ADHD and CD. PMID- 27280524 TI - Premorbid, clinical and cognitive correlates of primary negative symptoms in first-episode psychosis. AB - Negative symptoms are a core psychopathological dimension of psychotic disorders. Previous research on primary negative symptoms (PNS) mostly focused on chronic samples. Data regarding premorbid, clinical and cognitive correlates of PNS in the early illness course are limited and inconsistent. In this study, we assessed 355 Hong Kong Chinese adult patients presenting with first-episode psychosis (FEP) to early intervention service with an aim to examine the prevalence of PNS and its relationships with premorbid adjustment, clinical and cognitive profiles. PNS was defined as the presence of clinically significant negative symptoms excluding depression, positive symptoms and extrapyramidal signs. Results showed that 14.6% of patients exhibited PNS at service entry. PNS group had poorer premorbid social functioning, lower level of insight, and worse performance in Modified Wisconsin Card Sorting and digit symbol tests than non-PNS group. Logistic regression analysis showed that premorbid social functioning and digit symbol test score were independently associated with PNS. Our findings thus indicate that PNS are frequently observed in FEP patients. Deficits in proceeding speed, alongside impaired premorbid social functioning, might be specifically related to PNS in the early illness stage. PMID- 27280525 TI - Social cognition in schizophrenia: Factor structure of emotion processing and theory of mind. AB - Factor analytic studies examining social cognition in schizophrenia have yielded inconsistent results most likely due to the varying number and quality of measures. With the recent conclusion of Phase 3 of the Social Cognition Psychometric Evaluation (SCOPE) Study, the most psychometrically sound measures of social cognition have been identified. Therefore, the aims of the present study were to: 1) examine the factor structure of social cognition in schizophrenia through the utilization of psychometrically sound measures, 2) examine the stability of the factor structure across two study visits, 3) compare the factor structure of social cognition in schizophrenia to that in healthy controls, and 4) examine the relationship between the factors and relevant outcome measures including social functioning and symptoms. Results supported a one-factor model for the patient and healthy control samples at both visits. This single factor was significantly associated with negative symptoms in the schizophrenia sample and with social functioning in both groups at both study visits. PMID- 27280526 TI - Influence of cognition, premorbid adjustment and psychotic symptoms on psycho social functioning in first-episode psychosis. AB - OBJECTIVE: The aim of this study is to evaluate the relationship between psycho social functioning and symptoms, cognitive function, and premorbid adjustment, in patients with a first-episode psychosis. METHOD: Clinical data were obtained from 90 patients, who were assessed with the Disability Assessment Scale (DAS-sv), the Positive and Negative Syndrome Scale (PANSS), the Premorbid Adjustment Scale (PAS S) and with a battery of cognitive tests including Trail Making Tests A and B (TMTA- B), Continous Performance Test (CPT), some subscales of the Wechler Adult Intelligence Scale (WAIS), and the Verbal Learning Test Espana-Complutense (TAVEC). RESULTS: The results of the study suggest that psycho-social functioning in first-episode psychosis is significantly related to: positive, negative, excitative, affective and disorganized symptoms, social premorbid adjustment, cognitive flexibility, working memory, short term and long term memory. Of these, those which best explained psycho-social functioning are the positive and excitative symptoms, premorbid adjustment, flexibility and memory. CONCLUSIONS: These findings highlight the importance early intervention on cognitive and clinical variables to help provide a better psycho-social functioning in people with a first-episode of psychosis. PMID- 27280527 TI - Fear the serpent: A psychometric study of snake phobia. AB - Millions of people worldwide suffer from specific phobias. Almost any stimulus may trigger a phobic reaction, but snakes are among the most feared objects. Half of the population feel anxious about snakes and 2-3% meet the diagnostic criteria for snake phobia. Despite such a high ratio, only one instrument is commonly used, the Snake Questionnaire (SNAQ). The aim of this study was to develop a standardized Czech translation, describe its psychometric properties and analyze the distribution of snake fears. In a counter-balanced design 755 respondents were asked to complete the English and Czech SNAQ (first or last) with a 2-3 month delay; 300 of them completed both instruments. We found excellent test retest reliability (0.94), although the total scores differed significantly when the English version was administered first. The mean score was 5.80 and Generalized Linear Models revealed significant effects of sex and field of study (women and people with no biology education scored higher than men and biologists). A cut-off point for snake phobia as derived from a previous study identified 2.6% of the subjects as phobic. Finally, the score distribution was similar to other countries supporting the view that fear of snakes is universal. PMID- 27280528 TI - Preventing Mitochondrial DNA Diseases: One Step Forward, Two Steps Back. PMID- 27280529 TI - Factors Influencing the Prevalence of Mental Health Problems among Malay Elderly Residing in a Rural Community: A Cross-Sectional Study. AB - BACKGROUND AND PURPOSE: Mental health problems are common in old age, but frequently remain undetected and untreated. Mental health problems in the elderly are the result of a complex interaction of social, psychological and biological factors. The aim of this study is to determine the prevalence of mental health problems (depression, anxiety, and emotional stress) and their associated factors among the Malay elderly in a rural community of Perak, Malaysia. METHODS: It was a cross-sectional study. The Malay elderly aged 60 years and above were selected through convenient sampling to give a total of 230 respondents. The Depression, Anxiety, and Stress Scale (DASS-21) was used to assess the symptoms of depression, anxiety, and stress. Bivariate analyses were performed using chi square tests and multiple logistic regression analyses were conducted to determine the association between the factors and each of the mental health statuses assessed. RESULTS: The results showed that the prevalence of depression, anxiety, and stress among the elderly respondents was 27.8%, 22.6%, and 8.7%, respectively. The significant factors for depression were single elderly (Adjusted OR = 3.27, 95%CI 1.66, 6.44), living with family (Adjusted OR = 4.98, 95%CI 2.05, 12.10), and poor general health status (Adjusted OR = 2.28, 95%CI 1.20, 4.36). Living with family was the only significant factor for anxiety (Adjusted OR = 2.68, 95%CI 1.09, 6.57). There was no significant factor for stress. CONCLUSIONS: Depression and anxiety among the Malay elderly in the rural community were very worrying. More equity in health should be created or strengthened in order to intensify the opportunity to identify, diagnose, and treat those with mental health problems. Living arrangement in the rural community was an important factor that had influenced depression and anxiety. Therefore, further research is recommended for more comprehensive information, as a result of which appropriate intervention can be made. PMID- 27280530 TI - Correction: Low-Dose Irradiation Affects Expression of Inflammatory Markers in the Heart of ApoE -/- Mice. AB - [This corrects the article DOI: 10.1371/journal.pone.0119661.]. PMID- 27280531 TI - The Benefits of Self-Set Goals: Is Ego Depletion Really a Result of Self-Control Failure? AB - Research on ego depletion aims at explaining self-control failures in daily life. Both resource models and motivational accounts have been proposed for explanation. The aim of the present research was to test the different assumptions in two dual-task experiments where we operationalized ego depletion as a performance deviation from a self-set goal. In two experiments, we found evidence for this deviation contradicting motivational accounts of ego depletion: Participants experiencing ego depletion set themselves a stricter instead of a more lenient goal than controls, in that they chose to eat less cookies or wanted to perform better. Moreover, only participants without an initial self-control task could adhere to their self-set goal, whereas participants in the ego depletion condition in both experiments could not follow through with their more ambitious intentions. Taken together, our findings demonstrate the importance of goals in ego depletion research. PMID- 27280532 TI - Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity. AB - Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here. PMID- 27280533 TI - Early exposure to violence, relationship violence, and relationship satisfaction in adolescents and emerging adults: The role of romantic attachment. AB - OBJECTIVE: Violence in romantic relationships is highly prevalent in adolescence and early adulthood and is related to a wide array of negative outcomes. Although the scientific literature increasingly highlights potential risk factors for the perpetration of violence toward a romantic partner, integrative models of these predictors remain scarce. Using an attachment framework, the current study examines the associations between early exposure to violence, perpetration of relationship violence, and relationship satisfaction. We hypothesized that exposure to family violence fosters the development of attachment anxiety and avoidance, which in turn are related to relationship violence and low relationship satisfaction. METHOD: At Time 1, a sample of 1,252 (72.3% women) adolescents and emerging adults were recruited from high schools and colleges. Participants completed measures of exposure to family violence, attachment, perpetrated relationship violence and relationship adjustment. Three years later (Time 2), 234 of these participants agreed to participate in a follow-up assessment. Structural equation modeling was used to test cross-sectional and longitudinal models. RESULTS: The findings suggest that exposure to family violence predicts relationship violence both directly and indirectly through attachment anxiety, whereas attachment avoidance and relationship violence are predictors of relationship satisfaction. Longitudinal analyses also show that changes in romantic attachment are associated with changes in relationship violence and satisfaction. CONCLUSIONS: Romantic attachment is a significant target for the prevention and treatment of violence in intimate relationships involving adolescents or emerging adults. (PsycINFO Database Record PMID- 27280534 TI - Preparation and formation mechanism of BiOCl0.75I0.25 nanospheres by precipitation method in alcohol-water mixed solvents. AB - BiOCl0.75I0.25 crystals with irregular three-dimensional (3D) flower-like and hierarchical nanosphere-like structures were successfully synthesized in different alcohol-water mixed solvents by precipitation method. The primary formation mechanism of BiOCl0.75I0.25 nanospheres was investigated by taking water, monohydric alcohols (ethanol and isopropanol), and polyhydric alcohols (ethylene glycol, diethylene glycol, and glycerol) as solvents in the synthesis process. The obtained BiOCl0.75I0.25 samples were characterized by powder X-ray diffraction, Raman spectroscopy, field emission scanning electron microscopy, and nitrogen adsorption. Results showed that the alcohol solvents with different physical and chemical properties used in the synthesis process performed significant functions in directing the morphology and surface pore structure of BiOCl0.75I0.25 crystals. Meanwhile, BiOCl0.75I0.25 synthesized in various solvents exhibited morphology-dependent adsorption and photocatalytic degradation abilities in removing p-hydroxyphenylacetic acid (p-HPA), which was used as a model pollutant, in aqueous solutions under simulated solar light (lambda?290nm). In addition, the fabrication process of the crystal products was proposed through a series of time-dependent experiments. PMID- 27280535 TI - Comparison study of Cu-Fe-Ti and Co-Fe-Ti oxide catalysts for selective catalytic reduction of NO with NH3 at low temperature. AB - In this paper, a series of Cu-Fe-Ti and Co-Fe-Ti oxide catalysts were prepared by sol gel method. Cu-Fe-Ti and Co-Fe-Ti oxide catalysts showed the moderate catalytic activity for selective catalytic reduction (SCR) of NO with NH3 at low temperature. The catalysts with the molar ratio as 4:1:10 (M:Fe:Ti) were selected as the representatives for comparison of reaction properties and H2O resistance, which were denoted as Cu-Fe/TiO2 and Co-Fe/TiO2 respectively. The characterization results manifested Co-Fe/TiO2 owned more adsorption capacity of the reactants and Cu-Fe/TiO2 had better redox ability. The in situ DRIFTS experiments indicated that adsorbed NH3 species and nitrate species both exhibited reaction activity for Co-Fe/TiO2, while nitric oxide was only be reduced by adsorbed NH3 species through Eley-Rideal mechanism for Cu-Fe/TiO2 at 150 degrees C. Co-Fe/TiO2 exhibited the better resistance to H2O and its temperature window shifted towards the higher temperature in presence of 10vol% H2O, while the SCR activity of Cu-Fe/TiO2 was inhibited significantly in the whole temperature range investigated. The suppression of adsorption and activation for NH3 and NOx might be the reasons for the reversible inactivation, which was confirmed by the inhibitation of catalytic activities for separation NH3 and NO oxidation under the wet condition. We speculated that different thermal stability of adsorbed species and redox capacity of catalysts leaded to the different SCR behavior in absence and presence of H2O. PMID- 27280536 TI - Synthesis and enhanced NO2 gas sensing properties of ZnO nanorods/TiO2 nanoparticles heterojunction composites. AB - ZnO nanorods/TiO2 nanoparticles composites were synthesized and the effects of TiO2 concentrations on the NO2 sensing properties were studied in detail. The as prepared composites were characterized by XRD, SEM, TEM, PL, I-V and gas sensing measurements. The gas sensing results demonstrated that all the sensors based on ZnO/TiO2 nanocomposites exhibited much higher response than that of sensors based on pure ZnO nanorods. At the optimum operating temperature of 180 degrees C, the response values of the sensors based on ZnO/TiO2 nanocomposites decorated with TiO2 concentrations of 0, 3, 5, 8 and 10wt% were 50, 140, 310, 350 and 258, respectively. The PL and I-V results indicated that the increased charge transfer between the ZnO nanorods mediated by TiO2 nanoparticles enhanced the conductivity of the ZnO/TiO2 nanocomposites. The gas sensing mechanism was also carefully analyzed. The attachment of TiO2 nanoparticles onto ZnO nanorods induced more active sites for the adsorption of oxygen molecules (O(2)) and O(2) which can be more easily adsorbed on the surface of ZnO nanorods. Furthermore, the conduction channel of ZnO/TiO2 was much narrower as a result of the formation of heterojunction which may further contribute to the enhanced NO2 sensing properties. PMID- 27280537 TI - Insights into the morphology of human serum albumin and sodium dodecyl sulfate complex: A spectroscopic and microscopic approach. AB - Exploring and understanding the fundamental interaction between protein and surfactant is utmost important for various pharmaceutical and biomedical applications. However, very less is known about the arrangement of individual negatively charged sodium dodecyl sulfate (SDS) molecules on the human serum albumin (HSA). Here, we have investigated the morphology and mechanistic insights of complexation between HSA and SDS by means of photoluminescence (PL) spectroscopy, circular dichroism (CD) and PL microscopy using amine functionalized silicon quantum dot (Si QD) as an external luminescent marker. The present study is based on a unique and dynamic SDS-Si QD system. The synthesized allylamine-functionalized Si QDs show a distinct PL band centered at 455nm upon excitation at 375nm. At neutral pH, these Si QDs form ordered aggregates in the presence of 1mM SDS due to the hydrogen bonding interaction with the sulfate head groups of surfactants, which is manifested in the appearance of a large Stokes shifted luminescence band centered at 610nm. It has been observed that the PL intensity of SDS-Si QD aggregates at 610nm decreases gradually with concomitant increase in the PL intensity of monomeric Si QDs at 455nm upon increasing the concentration of HSA from 1 to 10MUM. These observations combined with PL lifetime, PL microscopy and CD results reveal that SDS forms micelle-like aggregates on the partially unfolded HSA mainly via electrostatic interaction between negatively charged sulfate head groups and positively charged residues of partially unfolded HSA. For the present HSA-SDS system, our results fit a model with type I "necklace and bead"-like structures, where micelle-like SDS aggregates wrap around by the partially unfolded HSA backbone. PMID- 27280538 TI - Graphene-based porous materials with tunable surface area and CO2 adsorption properties synthesized by fluorine displacement reaction with various diamines. AB - A mild, operationally simple and controllable protocol for preparing graphene based porous materials is essential to achieve a good pore-design development. In this paper, graphene-based porous materials with tunable surface area were constructed by the intercalation of fluorinated graphene (FG) based on the reaction of reactive CF bonds attached to graphene sheets with various amine terminated molecules. In the porous materials, graphene sheets are like building blocks, and the diamines covalently grafted onto graphene framework act as pillars. Various diamines are successfully grafted onto graphene sheets, but the grafting ratio of diamines and reduction degree of FG differ greatly and depend on the chemical reactivity of diamines. Pillared diamine molecules chemically anchor at one end and are capable of undergoing a different reaction on the other end, resulting in three different conformations of graphene derivatives. Nitrogen sorption isotherms revealed that the surface area and pore distribution of the obtained porous materials depend heavily on the size and structure of diamine pillars. CO2 uptake capacity characterization showed that ethylenediamine intercalated FG achieved a high CO2 uptake density of 18.0 CO2 molecules per nm(2) at 0 degrees C and 1.1bars, and high adsorption heat, up to 46.1kJmol(-1) at zero coverage. PMID- 27280539 TI - Food intake diet and sperm characteristics in a blue zone: a Loma Linda Study. AB - OBJECTIVES: The study examined the effect the life-long vegetarian diet on male fertility and focused on vegetarians living in the Loma Linda blue zone, a demographic area known for life longevity. The objective was to compare sperm characteristics of vegetarian with non-vegetarian males. STUDY DESIGN: The cross sectional observational study was based on semen analyses of 474 males from 2009 to 2013. Patients categorized themselves as either life-long lacto-ovo vegetarians (N=26; vegetable diet with dairy and egg products), vegans (N=5; strictly vegetables with no animal products) or non-vegetarians (N=443; no diet restrictions). Sperm quality was assessed using a computer-aided sperm analyzer and strict morphology and chromatin integrity were manually evaluated. RESULTS: Lacto-ovo vegetarians had lower sperm concentration (50.7+/-7.4M/mL versus non vegetarians 69.6+/-3.2M/mL, mean+/-S.E.M.). Total motility was lower in the lacto ovo and vegan groups (33.2+/-3.8% and 51.8+/-13.4% respectively) versus non vegetarians (58.2+/-1.0%). Vegans had lowest hyperactive motility (0.8+/-0.7% versus lacto-ovo 5.2+/-1.2 and non-vegetarians 4.8+/-0.3%). Sperm strict morphologies were similar for the 3 groups. There were no differences in rapid progression and chromatin integrity. CONCLUSIONS: The study showed that the vegetables-based food intake decreased sperm quality. In particular, a reduction in sperm quality in male factor patients would be clinically significant and would require review. Furthermore, inadequate sperm hyperactivation in vegans suggested compromised membrane calcium selective channels. However, the study results are cautiously interpreted and more corroborative studies are needed. PMID- 27280540 TI - Accuracy of antenatal ultrasound signs in predicting the risk for bowel atresia in patients with gastroschisis. AB - OBJECTIVE: Evaluate accuracy of prenatal ultrasound findings in predicting the risk of bowel atresia in patients with gastroschisis. METHODS: A retrospective study was conducted on 18 fetuses with a prenatal diagnostic of gastroschisis treated at University hospital of Saint Etienne France between 2002 and 2012. Ultrasound abnormalities were used to classify them into three groups: no ultrasound abnormality (n=4), oligohydramnios (n=9), intra-abdominal bowel dilatation >=20.5mm (n=5). Postnatal outcomes were compared between groups. The threshold value of 20.5mm for the prediction of atresia was determined through the receiver operator characteristics curve. RESULTS: In the group with oligohydramnios, intra uterine growth restriction were significantly more frequent (p=0.015) and three newborns had serositis including two with secondary complications after the initial surgery. In the group with major intra-abdominal bowel dilatation, all had a narrow defect <10mm significantly more than other fetuses (p=0.002). Intra-abdominal bowel dilatation reaching 20.5mm started at a mean gestational age significantly lower than that of the other fetuses (23.3 versus 29.7 weeks p=0.02). On the five fetuses presented intra-abdominal bowel dilatation >=20.5mm, four showed atresia and no other newborn has this complication (p=0.0016). The threshold value of 20.5mm has a sensitivity of 100% and a specificity of 92.9%. The area under the curve was equal to 96.4%. CONCLUSION: Intra-abdominal bowel dilatation >=20.5mm seems to be associated with the risk of postnatal atresia. MRI could help to clarify a complicated or uncertain ultrasound aspect. PMID- 27280541 TI - Outcome of pregnancies with spontaneous PPROM before 24+0 weeks' gestation. AB - OBJECTIVE: To examine the contemporary outcome in women with rupture of membranes (PPROM) before 24+0 weeks' gestation. STUDY DESIGN: Retrospective analysis of women with spontaneous PPROM before 24+0 weeks that were treated at the University of Tuebingen/Germany. The search of the database included common maternal and pregnancy characteristics as well as the neonatal outcomes. RESULTS: One hundred and one pregnancies fulfilled the inclusion criteria. 32 (31.7%) women opted for termination of pregnancy, which were excluded from further analysis. The gestational age at PPROM in the 69 women with an expectant management was 21.3 (IQR 19.1-22.6) weeks. 40 (58.0%) pregnancies carried on beyond 24+0 weeks. Multiple regression analysis indicated that the time of PPROM and the absence of oligo-/anhydramnios were associated with a prolongation beyond 24+0 weeks. In the 40 pregnancies that remained intact beyond 24+0 weeks' gestation, the fetuses were born at 27.7 (IQR 25.3-30.9) weeks. Survival without major complications was observed in 22 (55.0%) fetuses. Multiple regression analysis indicated that only the gestational age at the time of delivery was significantly associated with such an intact survival. CONCLUSION: In cases with PPROM there is a 60% chance of a prolongation beyond 24+0 weeks. About half of these fetuses will be discharged alive without major complications. PMID- 27280542 TI - Quantitative fetal fibronectin predicts preterm birth in women with bulging fetal membranes. AB - OBJECTIVE: To assess the predictive value of quantitative fetal fibronectin (fFN) concentration in cervicovaginal fluid for spontaneous preterm birth in women with bulging fetal membranes. STUDY DESIGN: This was a prospective observational study from five UK tertiary centres of a cohort of women with singleton pregnancy and bulging fetal membranes presenting between 18 and 32 weeks of gestation (n=62), in the period 2010-2014. fFN concentrations in cervicovaginal fluid were measured both quantitatively and qualitatively at presentation in all women. Predictive statistics and receiver operating characteristic (ROC) curves were calculated for both tests to predict spontaneous preterm birth within 14 days from testing and before 34 weeks of gestation. RESULTS: 62 eligible women with bulging fetal membranes were recruited from screening of 2571 women at high risk of preterm birth. The median gestational age was 24(+0) (LQ-UQ, 21(+2)-25(+3)) at presentation and 34(+4) (25(+2)-39(+0)) at delivery, with a median time from testing to delivery of 58 days (17-110). Concentration of quantitative fFN at presentation correlated negatively with time to delivery (Spearman's rs=-0.615, p<0.001). The area under the ROC curve for quantitative fFN testing was 0.81 (95% CI 0.69-0.94) for prediction of spontaneous preterm birth within 14 days, and 0.84 (0.73-0.95) before 34 weeks of gestation. CONCLUSION: Quantitative fFN has a role in predicting spontaneous preterm birth even in women with bulging fetal membranes, suggesting that fFN leakage could potentially be an active process. This may aid the clinical management of this high-risk group in the future. PMID- 27280543 TI - Cavernous sinus invasion by pituitary adenomas: role of endoscopic endonasal surgery. AB - BACKGROUND: Cavernous sinus (CS) invasion is one of the most unfavorable features of pituitary adenomas. The most widely used classification was proposed by Knosp in 1993 and revised in 2015. The aim of this study is to extend our previous experience by comparing the pre-operative neuroradiological assessment with the intra-operative endoscopic endonasal inspection in order to evaluate the real rate of CS invasion and analyze its correlation with the surgical outcome. METHODS: Consecutive patients, who have undergone endoscopic endonasal surgery for a pituitary adenoma with Knosp grade greater than 1, have been included in this study. The intra-operative CS invasion was assesses basing on surgical reports. The surgical outcome has been evaluated with MRI, endocrinological, visual and neurological evaluation have been performed 3 months after surgery and then annually. RESULTS: The series included 402 patients. Male-female ratio was 1:1 and median age was 56 years (range 15-85). We observed that 43% of cases with Knosp grade greater than 1 presented no CS invasion on surgical inspection. Knosp grade 4 was the only one corresponding in all cases to a real CS invasion. Radical tumor removal was achieved in 60%. while endocrinological remission was obtained in 37% of functioning adenomas. Better results were observed for lower Knosp grades. CONCLUSIONS: The endoscopic endonasal inspection is the most effective technique to detect CS invasion. Indeed, it can provide a direct visualization of the medial wall, permitting the assessment of its invasion and the management of those cases with diffuse involvement. We confirm that the revision to the Knosp classification has improved its prognostic role. PMID- 27280544 TI - Endonasal endoscopic transsphenoidal excision of tuberculum sellae meningiomas: a systematic review. AB - INTRODUCTION: The endonasal endoscopic approach (EEA) for the resection of tuberculum sellae meningiomas (TSMs) has, more recently, been advocated as an alternative approach to deal with this challenging tumor. The aim of this study was to conduct a systematic review of publications of TSMs excised through the transsphenoidal route in the past 10 years and review data on the extent of excision, visual outcomes and complication rates. EVIDENCE ACQUISITION: We performed a thorough systematic review of the medical literature following the PRISMA guidelines. A medical librarian retrieved a list of 3443 articles published from 2006-2015 from the MEDLINE, EMBASE and Cochrane Central databases. Two of the authors independently screened for titles and abstracts and excluded 3340 of them. We reviewed the full text of the remaining 103 articles and included in our analysis 12 that met the following inclusion criteria: 1) 5 or more cases reported; 2) the extent of resection, visual outcomes and complication rates that were specifically documented for TSMs excised through the transsphenoidal route. EVIDENCE SYNTHESIS: Twelve studies that included 150 patients were analyzed. The mean age was 55 years. The mean tumor volume, reported in 2 studies, was 6.6 cc and mean maximum diameter, reported in 11 studies, was 25 mm. The gross total resection rate was 77.2%. Vision improved in 79.5% of cases and deteriorated in 7.3%. CSF leak postoperatively occurred in 15.3% of patients. In the 11 studies that reported hormonal outcomes, there was a 9.4% transient hyponatremia or diabetes insipidus and 2.2% of patients developed a new permanent endocrine dysfunction. A symptomatic vascular injury was reported in 2.6% of patients. There was one mortality (0.6%). CONCLUSIONS: The endonasal endoscopic transsphenoidal excision of TSMs is a feasible, safe and effective surgical option with a low morbidity and mortality. The use of this approach has evolved in the last 10 years and in some centers has replaced the transcranial route for selected cases. Given the limited availability and heterogeneity of comparative observational studies, a direct comparison with transcranial approaches was not performed for the purpose of this review analysis. Likewise, from an epidemiological and statistical perspective a meta-analysis was deemed inappropriate. PMID- 27280545 TI - Endoscopic trans-sphenoidal surgery for petroclival and clival meningiomas. AB - Petroclival meningiomas are challenging lesions to manage independently of the selected surgical approach and are unique tumors in the type of pathological displacement of the surrounding anatomy. They also represent one of the most controversial entities with regard to approach selection, especially when deciding between an open versus endonasal route. When choosing an approach to the intradural portion of the petroclival region, the location of critical neurovascular structures relative to the lesion must be anticipated, including the abducens and trigeminal nerves. The role of the expanded endoscopic endonasal approach (EEA) in the management of ventral posterior fossa meningiomas is still restricted due to limited surgical indications in selected cases. It is a safe alternative for the rare cases of meningiomas with most part of its dural base at the midline clival region, and it may be used as solely or combination of other approaches. Thus, appropriate case selection may optimize the advantages of the approach and reduce morbidity of this complex pathology. We discuss in this review article the main advantages and limitations of the EEA for clival and petroclival meningiomas. PMID- 27280546 TI - Transorbital endoscopic approaches to the skull base: current concepts and future perspectives. AB - INTRODUCTION: Transorbital endoscopic surgery is one of the most recent fields of skull base surgery. This paper presents the emerging applications of transorbital endoscopic approaches to the skull base and their current results on the treatment of selected extradural and intradural lesions, based on a review of meta-analysis and recent clinical series. EVIDENCE ACQUISITION: A PubMed, Cochrane and Ovid search for articles published from 2000 to 2015 was performed using the search terms "endoscopic skull base surgery", "transorbital endoscopic approach", and "transorbital neuroendoscopic surgery". No anatomical or preclinical studies were included in the present review. Among the clinical case series available, only those describing transorbital approaches to the skull base have been considered, excluding from the analysis the studies addressing the orbit and orbital pathologies. EVIDENCE SYNTHESIS: Although performed in extremely selected cases, there is a growing body of evidence suggesting that this technique may be effective for the treatment of cerebrospinal fluid leaks, for the drainage of epidural abscess or hematoma, and for the removal of several skull base tumors such as spheno-orbital meningioma. For the treatment of intradural pathologies there is only anecdotal evidence suggesting effectiveness and safety. Factors that may contribute to the enhanced efficacy compared to traditional external approaches were the acceptable complication rates, the reduced hospitalization time and limited morbidity for the patients, avoiding the need for large external craniotomies and brain retraction. CONCLUSIONS: Minimally invasive endoscopic skull base surgery has substantially evolved in the last decades through the collaboration of different teams around the world. The transorbital endoscopic approaches directed to the anterior and middle cranial base may represent safe and feasible techniques with great potential for new applications in the nearby future. PMID- 27280547 TI - Hydroxyl-Assisted Carbonylation of Alkenyltin Derivatives: Development and Application to a Formal Synthesis of Tubelactomicin A. AB - Alkenyltin derivatives flanked by a hydroxyl group are subject to methoxycarbonylation when treated with catalytic amounts of Pd(OAc)2 and Ph3As in MeOH under a CO atmosphere; key to success is the use of 1,4-benzoquinone as a stoichiometric oxidant in combination with trifluoroacetic acid as a cocatalyst. The acid lowers the LUMO of the quinone and likely marshals the critical assembly of the substrates. Under the optimized conditions, competing proto-destannation is marginal; the method proved compatible with various (acid sensitive) functional groups and was applied to a short formal total synthesis of the antibiotic tubelactomicin A. PMID- 27280549 TI - Using only behaviours to assess infant pain: a painful compromise? PMID- 27280548 TI - Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection. AB - Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naive HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-gamma, MIP-1beta) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID- 27280550 TI - Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus. AB - Pharmacoperones correct the folding of otherwise misfolded protein mutants, restoring function (i.e., providing "rescue") by correcting their trafficking. Currently, most pharmacoperones possess intrinsic antagonist activity because they were identified using methods initially aimed at discovering such functions. Here, we describe an ultra-high-throughput homogeneous cell-based assay with a cAMP detection system, a method specifically designed to identify pharmacoperones of the vasopressin type 2 receptor (V2R), a GPCR that, when mutated, is associated with nephrogenic diabetes insipidus. Previously developed methods to identify compounds capable of altering cellular trafficking of V2R were modified and used to screen a 645,000 compound collection by measuring the ability of library compounds to rescue a mutant hV2R [L83Q], using a cell-based luminescent detection system. The campaign initially identified 3734 positive modulators of cAMP. The confirmation and counterscreen identified only 147 of the active compounds with an EC50 of <=5 uM. Of these, 83 were reconfirmed as active through independently obtained pure samples and were also inactive in a relevant counterscreen. Active and tractable compounds within this set can be categorized into three predominant structural clusters, described here, in the first report detailing the results of a large-scale pharmacoperone high-throughput screening campaign. PMID- 27280551 TI - Flow Cytometric Method for the Detection of Flavonoids in Cell Lines. AB - Here, we describe an easy-to-use flow cytometric method using diphenylboric acid 2-amino ethyl ester (DPBA) stain for the detection of flavonoids in cells from human/animal origin. Flavonoid bioavailability and bioactivity depend on structure, conjugation and the cell type to which they are presented. We have studied cellular uptake of five flavonoids with different structures and conjugation forms. First, parameters including fixation method, technical and batch variability, and concentration were optimized. Second, uptake of two aglycones-quercetin and hesperetin-and their corresponding glycosides-rutin and hesperidin-in Caco-2 cells was compared. Third, the aglycone quercetin, glycoside rutin, and glucuronide baicalin were added to the Caco-2, HepG2, and CHO-K1 cell lines at 1, 10, and 20 uM concentrations and cellular uptake was measured after 1, 4, and 7 h. We conclude that quercetin was taken up by cells in a dose dependent way, and that HepG2 cells had the highest uptake factors, followed by CHO-K1 and Caco-2 cells. Confocal microscopy showed cell type-dependent localization of quercetin in the cell membrane and cytoplasm. No uptake of flavonoid glycosides was detected. This flow cytometric method can be used for future research unravelling mechanisms behind flavonoid bioactivity in health and disease at the cellular level. PMID- 27280552 TI - Comparison of children's food and beverage intakes with national recommendations in New York City child-care centres. AB - OBJECTIVE: The present study compared foods and beverages provided to and consumed by children at child-care centres in New York City (NYC) with national nutrition recommendations. DESIGN: The study used survey, observational and centre record data collected from child-care centres. Food and beverage intakes from two days of observation and amounts of energy and nutrients were estimated using the US National Cancer Institute's Automated Self-Administered 24 h Recall system. SETTING: Meal and snack time at 108 child-care centres in low-income communities in NYC. SUBJECTS: Children aged 3-4 years old in classrooms selected by the directors of the participating child-care centres. RESULTS: Foods and beverages provided to and consumed by children (n 630) met >50 % of the Dietary Reference Intake (DRI) for most nutrients. Intakes of fibre and vitamins D and E were 50 % of the recommended average daily intake amounts for total grains, fruits and fruit juices, and dairy, but <50 % of the recommended amounts for whole grains, protein foods and vegetables. Intake of oils was below the allowance for energy levels, but foods and beverages with solid fats and added sugars exceeded the limits by 68 %. CONCLUSIONS: Providing more whole grains, vegetables and low-fat dairy and fewer foods with solid fats and added sugars may improve children's diet quality when at child-care centres. Centre staff may need training, resources and strategies in order to meet the nutrition recommendations. PMID- 27280553 TI - Anticholinergic effect on cognition (AEC) of drugs commonly used in older people. AB - OBJECTIVE: Use of anticholinergic drugs in older people is associated with increased risk of cognitive decline and of dementia and death. METHOD: We identified drugs widely used in older people and attempted to classify their anticholinergic effect on cognition (AEC) according to our three-point scale which scored AEC according to in vitro anticholinergic potency, capacity to cross the blood-brain barrier and statements made in standard texts. RESULTS: In total, 165 drugs were examined. We identified 21 drugs with an AEC score of 3, 18 with a score of 2, 21 with a score of 1 and 62 with a score of 0. Owing to insufficient information, we were unable to classify 43 drugs. CONCLUSIONS: A large number of drugs commonly used in older people are likely to be associated with cognitive impairment. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27280554 TI - Spatial Ecology of the American Crocodile in a Tropical Pacific Island in Central America. AB - Conservation of large predators has long been a challenge for biologists due to the limited information we have about their ecology, generally low numbers in the wild, large home ranges and the continuous expansion of human settlements. The American crocodile (Crocodylus acutus) is a typical apex predator, that has suffered from all of these characteristic problems, especially the latter one. Humans have had a major impact on the recovery of this species throughout its range, even though most of the countries it inhabits have banned hunting. The last decade has made it clear that in order to implement sound conservation and management programs, we must increase our understanding of crocodile spatial ecology. However, in only two countries where American crocodiles have telemetry studies even been published. Herein we have characterized the spatial ecology of C. acutus on Coiba Island, Panama, by radio-tracking (VHF transmitters) 24 individuals between 2010 and 2013, to determine movement patterns, home range, and habitat use. We have then compared our findings with those of previous studies to develop the most comprehensive assessment of American crocodile spatial ecology to date. Females showed a higher average movement distance (AMD) than males; similarly, adults showed a higher AMD than sub-adults and juveniles. However, males exhibited larger home ranges than females, and concomitantly sub adults had larger home ranges than juveniles, hatchlings, and adults. There was an obvious relationship between seasonal precipitation and AMD, with increased AMD in the dry and "low-wet" seasons, and reduced AMD during the "true" wet season. We found disaggregate distributions according to age groups throughout the 9 habitat types in the study area; adults and hatchlings inhabited fewer habitat types than juveniles and sub-adults. These sex- and age-group discrepancies in movement and habitat choice are likely due to the influences of reproductive biology and Coiba's precipitation cycle. Juveniles also showed distinct movement patterns and home ranges; however, with sexual maturation and development, these behaviors became more characteristic of adults and sub-adults. Ours is one of a very small number of studies that will allow future management and conservation planning to be based on the comprehensive integration of the spatial ecology of a Neotropical crocodylian apex predator. PMID- 27280555 TI - Nurses from the Mobile Emergency Service: profile and developed activities. PMID- 27280556 TI - Hospital discharge of premature newborns: the father's experience. PMID- 27280557 TI - Epidemiological characteristics and causes of deaths in hospitalized patients under intensive care. PMID- 27280558 TI - Transcultural adaptation and validation of the Brazilian version of Treatment Spirituality/Religiosity Scale. PMID- 27280559 TI - Quality of life assessment for health promotion groups. PMID- 27280560 TI - Pressure ulcer healing with Plenusdermax(r) Calendula officinalis L. extract. PMID- 27280561 TI - Overweight in young adult students: the vulnerability of a distorted self perception of body image. PMID- 27280562 TI - Attitudes and pleasure/suffering in mental health work. PMID- 27280564 TI - Humanization knowledge of undergraduate nursing students. PMID- 27280563 TI - Prevention of vertical mother-to-child transmission of HIV: care and adhesion provided by couples. PMID- 27280565 TI - Direct cost of dressings for pressure ulcers in hospitalized patients. PMID- 27280566 TI - Social network of adolescents under probation from the perspective of public health. PMID- 27280567 TI - Nursing diagnoses in intensive care: cross-mapping and NANDA-I taxonomy. PMID- 27280568 TI - Nursing instrument to attend mothers who recently gave birth in primary health care. PMID- 27280569 TI - Family farming and human and environmental health conservation. PMID- 27280570 TI - Prevalence of medication therapy adherence in the elderly and related factors. PMID- 27280571 TI - Social representations of nursing students about hospital assistance and primary health care. PMID- 27280572 TI - Stress and cardiovascular risk: multi-professional intervention in health education. PMID- 27280573 TI - Influence of the Sao Paulo State innovative models on Brazil's mental health policy. PMID- 27280574 TI - Teaching airway management with laryngeal mask: randomized controlled trial. PMID- 27280575 TI - Characterization of undergraduate nursing courses according to the National Student Performance Exam. PMID- 27280576 TI - Prevalence and factors associated with traffic accidents involving motorcycle taxis. PMID- 27280577 TI - Suicidal behavior among drug addicts. PMID- 27280578 TI - Anxiety in the preoperative period of heart surgery. PMID- 27280579 TI - Interventions that facilitate adherence to Pap smear exam: integrative review. PMID- 27280581 TI - Aligning for accountable care: Strategic practices for change in accountable care organizations. AB - BACKGROUND: Alignment within accountable care organizations (ACOs) is crucial if these new entities are to achieve their lofty goals. However, the concept of alignment remains underexamined, and we know little about the work entailed in creating alignment. PURPOSE: The aim of this study was to develop the concept of aligning by identifying and describing the strategic practices administrators use to align the structures, processes, and behaviors of their organizations and individual providers in pursuit of accountable care. APPROACH: We conducted 2 year qualitative case studies of four ACOs that have assumed full risk for the costs and quality of care for defined populations. FINDINGS: Five strategic aligning practices were used by all four ACOs. Informing both aligns providers' understandings with the goals and value proposition of the ACO and aligns the providers' attention with the drivers of performance. Involving both aligns ACO leaders' understandings with the realities facing providers and aligns the policies of the ACO with the needs of providers. Enhancing both aligns the operations of individual provider practices with the operations of the ACO and aligns the trust of providers with the ACO. Motivating aligns what providers value with the goals of the ACO. Finally, evolving is a metapractice of learning and adapting that guides the execution of the other four practices. PRACTICE IMPLICATIONS: Our findings suggest that there are second-order cognitive (e.g., understandings and attention) and cultural (e.g., trust and values) levels of alignment, as well as a first-order operational level (organizational structures, processes, and incentives). A well-aligned organization may require ongoing repositioning at each of these levels, as well as attention to both cooperative and coordinative dimensions of alignment. Implications for research and practice are discussed. PMID- 27280580 TI - Nonlinear associations between plasma cholesterol levels and neuropsychological function. AB - OBJECTIVE: Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. METHOD: Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as <70 vs. 70+) as an effect modifier. RESULTS: A significant quadratic effect of Total Cholesterol2 * Age was identified for Logical Memory II (b = -.0013, p = .039), such that the 70+ group performed best at high and low levels of total cholesterol than at midrange total cholesterol (U-shaped) and the <70 group performed worse at high and low levels of total cholesterol than at midrange total cholesterol (inverted U shape). Similarly, significant U- and J-shaped effects of LDL Cholesterol2 * Age were identified for Visual Reproduction II (b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. CONCLUSIONS: Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record PMID- 27280582 TI - Nursing Home Administrator Quality Improvement Self-Efficacy Scale. AB - BACKGROUND: Nursing home (NH) quality improvement (QI) is challenging. The critical role of NH leaders in successful QI is well established; however, current options for assessing the QI capabilities of leaders such as the licensed NH administrator are limited. PURPOSE: This article presents the development and preliminary validation of an instrument to measure NH administrator self-efficacy in QI. METHODOLOGY/APPROACH: We used a mixed-methods cross-sectional design to develop and test the measure. For item generation, 39 NH leaders participated in qualitative interviews. Item reduction and content validity were established with a sample of eight subject matter experts. A random sample of 211 administrators from NHs with the lowest and highest Centers for Medicare and Medicaid Services Five-Star Quality ratings completed the measure. We conducted exploratory and confirmatory factor analyses and tested the measure for internal reliability and convergent, discriminant, and known group validity. FINDINGS: The final measure included five subscales and 32 items. Confirmatory factor analysis reaffirmed the factorial structure with good fit indices. The new measure's subscales correlated with valid measures of self-efficacy and locus of control, supporting the measure's convergent and discriminant validity. Significant differences in most of the subscales were found between the objective (Centers for Medicare and Medicaid Services Five-Star Quality rating) and subjective (Self-Rated Facility QI Index) quality outcomes, supporting the measure's known group validity. PRACTICE IMPLICATIONS: The instrument has usefulness to both NH organizations and individual NH administrators as a diagnostic tool to identify administrators with higher/lower chances of successfully implementing QI. Organizations and individuals can use this diagnostic to identify the administrator's professional development needs for QI, in general, and specific to the instrument's five subscales, informing directions for in-house training, mentoring, and outside professional development. Attending to NH administrators' QI professional development needs prior to implementing QI holds promise to enhance the chances for successful implementation of QI, which is urgently needed in many NHs. PMID- 27280583 TI - Insider versus outsider executive succession: The relationship to hospital efficiency. AB - BACKGROUND: The relationship between Chief Executive Officer (CEO) succession and hospitals' competitive performance is an area of interest for health services researchers. Of particular interest is the impact on overall strategic direction and health system performance that results from selecting a CEO from inside the firm as opposed to seeking outside leadership. Empirical work-to-date has yielded mixed results. Much of this variability has been attributed to design flaws; however, in the absence of a clear message from the evidence, the preference for hiring "outsiders" continues to grow. PURPOSE: This paper investigates on the extent to which insider CEO succession versus outsider succession impacts hospitals' competitive advantage vis-a-vis a sample of organizations that compete in the same sector. METHODS: A hospital matching protocol based on propensity scores is used to control for endogeneity and makes comparisons of productivity across organizations through the use of stochastic frontier estimation. FINDINGS: Succession negatively impacts hospitals' productivity, and firms with outsider CEO succession events closed the gap toward the competitive advantage frontier faster than comparable firms with insider successions. PRACTICE IMPLICATIONS: More research needs to be done on succession planning and its impact on CEO turnover. PMID- 27280584 TI - Knowledge, Attitudes, and Practices Associated with Chronic Kidney Disease in Northern Tanzania: A Community-Based Study. AB - BACKGROUND: Non-communicable diseases (NCDs) are a leading cause of death among adults in sub-Saharan Africa, and chronic kidney disease (CKD) is a growing public health threat. Understanding knowledge, attitudes, and practices associated with NCDs is vital to informing optimal policy and public health responses in the region, but few community-based assessments have been performed for CKD. To address this gap, we conducted a cross-sectional survey of adults in northern Tanzania using a validated instrument. METHODS: Between January and June 2014, we administered a structured survey to a random sample of adults from urban and rural communities. The validated instrument consisted of 25 items designed to measure knowledge, attitudes, and practices associated with kidney disease. Participants were also screened for CKD, diabetes, hypertension, and human immunodeficiency virus. RESULTS: We enrolled 606 participants from 431 urban and rural households. Knowledge of the etiologies, symptoms, and treatments for kidney disease was low (mean score 3.28 out of 10; 95% CI 2.94, 3.63). There were no significant differences by CKD status. Living in an urban setting and level of education had the strongest independent associations with knowledge score. Attitudes were characterized by frequent concern about the health (27.3%; 20.2, 36.0%), economic (73.1%; 68.2, 77.5%), and social impact (25.4%; 18.6, 33.6%) of kidney disease. Practices included the use of traditional healers (15.2%; 9.1, 24.5%) and traditional medicines (33.8%; 25.0, 43.9%) for treatment of kidney disease as well as a willingness to engage with mobile-phone technology in CKD care (94.3%; 90.1, 96.8%). CONCLUSIONS: Community-based adults in northern Tanzania have limited knowledge of kidney disease. However, there is a modest knowledge base upon which to build public health programs to expand awareness and understanding of CKD, but these programs must also consider the variety of means by which adults in this population meet their healthcare needs. Finally, our assessment of local attitudes suggested that such public health efforts would be well-received. PMID- 27280586 TI - Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms. AB - New treatments for inflammatory bowel disease are of interest due to high rate of remission failure. Natural products have been effective in IBD therapeutics as they have multiple constituents. The aim of the present study was to evaluate the effect of Flaxseed extract (Fs.Cr) on ulcerative colitis and identify the possible mechanisms involved. Colitis was induced by intrarectal administration of 6% AA in BALB/c mice. Colonic mucosal damage was assessed after 24h by calculating disease activity index (DAI), macroscopic and histological damage scores, biochemical measurement of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total glutathione activities. Since cytokines are involved in exacerbating inflammatory cascade with emerging role of innate immune cytokines in IBD therapeutics, we hence assessed the effect on the levels of TNF-alpha, IFN-gamma and IL-17, at 6, 12 and 24h by ELISA. Fs.Cr ameliorated the severity of AA colitis as evident by improved DAI, macroscopic damage and the histopathological scores along with restoration of goblet cells. Fs.Cr decreased MDA and MPO activities and enhanced antioxidant activity compared to the AA group. Finally, Fs.Cr in doses (300 and 500mg/kg) decreased TNF-alpha and IFN-gamma levels at all time points with simultaneous increase in IL-17 levels at 24h as compared to the AA group. These results suggest that Fs.Cr ameliorates the severity of AA colitis by reducing goblet cell depletion, scavenging oxygen-derived free radicals, reduce neutrophil infiltration that may be attributed due to decreasing IFN-gamma and TNF-alpha and increasing IL-17 levels. PMID- 27280588 TI - Reshaping the global health agenda: female genital cutting. PMID- 27280587 TI - Knockdown of placental growth factor (PLGF) mitigates hyperoxia-induced acute lung injury in neonatal rats: Suppressive effects on NFkappaB signaling pathway. AB - Although supplemental high-level oxygen treatment can promote the survival of premature infants, hyperoxia may adversely induce acute lung injury (ALI) in newborns. Our prior work illustrated that hyperoxic exposure could enhance the release of placental growth factor (PLGF) in the lungs of neonatal rats. We therefore postulated that PLGF contributed to hyperoxic ALI in newborns and evaluated the anti-PLGF treatment mediated by systematic delivery of lentivirus in hyperoxic ALI in this study. Lentivirus particles containing PLGF specific shRNA were injected into neonatal rats prior to hyperoxic exposure (90% oxygen for 72h) to inhibit PLGF expression. Hyperoxia induced oxidative damages in lung tissues as evidenced by the increased malondialdehyde and myeloperoxidase, and the decreased antioxidant superoxide dismutase. Also, hyperoxia caused excessive infiltration of inflammatory cells and overproduction of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta and interleukin-6) in rat lung tissue. These pathological alterations were partly reversed by PLGF shRNA delivery. The expression levels and activities of metalloproteinase (MMP)-2 and MMP9 were up-regulated in response to hyperoxia, whereas down-regulated when PLGF was inhibited. Moreover, PLGF shRNA inhibited nuclear factor kappa B (NFkappaB) signaling delivery in hyperoxic rat lungs. Additionally, exogenous PLGF-induced activation of MMPs in rat RLE-6TN alveolar epithelial cells was suppressed by NFkappaB inhibitor pyrrolidine dithiocarbamate. These results suggest that therapy targeting PLGF may be beneficial for infants with hyperoxic ALI. PMID- 27280585 TI - Novel Hydrogenosomes in the Microaerophilic Jakobid Stygiella incarcerata. AB - Mitochondrion-related organelles (MROs) have arisen independently in a wide range of anaerobic protist lineages. Only a few of these organelles and their functions have been investigated in detail, and most of what is known about MROs comes from studies of parasitic organisms such as the parabasalid Trichomonas vaginalis Here, we describe the MRO of a free-living anaerobic jakobid excavate, Stygiella incarcerata We report an RNAseq-based reconstruction of S. incarcerata's MRO proteome, with an associated biochemical map of the pathways predicted to be present in this organelle. The pyruvate metabolism and oxidative stress response pathways are strikingly similar to those found in the MROs of other anaerobic protists, such as Pygsuia and Trichomonas This elegant example of convergent evolution is suggestive of an anaerobic biochemical 'module' of prokaryotic origins that has been laterally transferred among eukaryotes, enabling them to adapt rapidly to anaerobiosis. We also identified genes corresponding to a variety of mitochondrial processes not found in Trichomonas, including intermembrane space components of the mitochondrial protein import apparatus, and enzymes involved in amino acid metabolism and cardiolipin biosynthesis. In this respect, the MROs of S. incarcerata more closely resemble those of the much more distantly related free-living organisms Pygsuia biforma and Cantina marsupialis, likely reflecting these organisms' shared lifestyle as free-living anaerobes. PMID- 27280590 TI - Three New Escherichia coli Phages from the Human Gut Show Promising Potential for Phage Therapy. AB - With the emergence of multi-drug resistant bacteria the use of bacteriophages (phages) is gaining renewed interest as promising anti-microbial agents. The aim of this study was to isolate and characterize phages from human fecal samples. Three new coliphages, phiAPCEc01, phiAPCEc02 and phiAPCEc03, were isolated. Their phenotypic and genomic characteristics, and lytic activity against biofilm, and in combination with ciprofloxacin, were investigated. All three phages reduced the growth of E. coli strain DPC6051 at multiplicity of infection (MOI) between 10-3 and 105. A cocktail of all three phages completely inhibited the growth of E. coli. The phage cocktail also reduced biofilm formation and prevented the emergence of phage-resistant mutants which occurred with single phage. When combined with ciprofloxacin, phage alone or in cocktail inhibited the growth of E. coli and prevented the emergence of resistant mutants. These three new phages are promising biocontrol agents for E. coli infections. PMID- 27280592 TI - Comparative accuracy of fitness tracking modalities in quantifying energy expenditure. AB - The purpose of this study is to compare the accuracy of wrist-worn, consumer grade pedometers and earbud sensor technology in quantifying energy expenditure. Nineteen participants (24.6 +/- 3.1 years) performed 5 min exercise stages on a treadmill (80.5 m/min, 107.3 m/min, 134.1 m/min and 160.9 m/min) while measuring energy expenditure via the Fitbit Charge pedometer and Jabra Sport Pulse Wireless Earbuds, comparing with indirect calorimetry. Paired samples t-tests were used to calculate differences and Pearson correlations to examine associations between kcals measured from the Fitbit and Jabra earbuds from indirect calorimetry. Results indicate significant underestimations of kcals for both devices at all speeds except one (Jabra earbuds at 107.3 m/min). Moderate correlations were observed for the Fitbit at 107.3 m/min and 107.3 m/min, and 134.1 m/min for the Jabra earbuds. Both devices considerably underestimated kcals, suggesting that caution be used when incorporating such data into fitness/health goals. PMID- 27280591 TI - Short Stature: Comparison of WHO and National Growth Standards/References for Height. AB - The use of appropriate growth standards/references is of significant clinical importance in assessing the height of children with short stature as it may determine eligibility for appropriate therapy. The aim of this study was to determine the impact of using World Health Organization (WHO) instead of national growth standards/references on height assessment in short children. Data were collected from routine clinical practice (1998-2014) from nine European countries that have available national growth references and were enrolled in NordiNet(r) International Outcome Study (IOS) (NCT00960128), a large-scale, non interventional, multinational study. The patient cohort consisted of 5996 short pediatric patients diagnosed with growth hormone deficiency (GHD), Turner syndrome (TS) or born small for gestational age (SGA). The proportions of children with baseline height standard deviation score (SDS) below clinical cut off values (-2 SDS for GHD and TS; -2.5 SDS for SGA) based on national growth references and WHO growth standards/references were compared for children aged <5 years and children aged >=5 years. In seven of the countries evaluated, significantly fewer children aged >=5 years with GHD (22%; P<0.0001), TS (21%; P<0.0001) or born SGA (32%; P<0.0001) had height below clinical cut-off values using WHO growth references vs. national references. Likewise, among children aged <5 years in the pooled analysis of the same seven countries, a significantly lower proportion of children with GHD (8%; P<0.0001), TS (12%; P = 0.0003) or born SGA (12%; P<0.0001) had height below clinical cut-off values using WHO growth standards vs. national references. In conclusion, in NordiNet(r) IOS the number of patients misclassified using WHO growth standards/references was significantly higher than with national references. This study highlights that, although no growth reference has 100% sensitivity for identifying growth disorders, the most recent national or regional growth charts may offer the most appropriate tool for monitoring childhood growth in Europe. PMID- 27280597 TI - Correction: Comparative Developmental Transcriptomics Reveals Rewiring of a Highly Conserved Gene Regulatory Network during a Major Life History Switch in the Sea Urchin Genus Heliocidaris. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002391.]. PMID- 27280593 TI - Improving Image Quality of On-Board Cone-Beam CT in Radiation Therapy Using Image Information Provided by Planning Multi-Detector CT: A Phantom Study. AB - PURPOSE: The aim of this study was to improve the image quality of cone-beam computed tomography (CBCT) mounted on the gantry of a linear accelerator used in radiation therapy based on the image information provided by planning multi detector CT (MDCT). METHODS: MDCT-based shading correction for CBCT and virtual monochromatic CT (VMCT) synthesized using the dual-energy method were performed. In VMCT, the high-energy data were obtained from CBCT, while the low-energy data were obtained from MDCT. An electron density phantom was used to investigate the efficacy of shading correction and VMCT on improving the target detectability, Hounsfield unit (HU) accuracy and variation, which were quantified by calculating the contrast-to-noise ratio (CNR), the percent difference (%Diff) and the standard deviation of the CT numbers for tissue equivalent background material, respectively. Treatment plan studies for a chest phantom were conducted to investigate the effects of image quality improvement on dose planning. RESULTS: For the electron density phantom, the mean value of CNR was 17.84, 26.78 and 34.31 in CBCT, shading-corrected CBCT and VMCT, respectively. The mean value of %Diff was 152.67%, 11.93% and 7.66% in CBCT, shading-corrected CBCT and VMCT, respectively. The standard deviation within a uniform background of CBCT, shading corrected CBCT and VMCT was 85, 23 and 15 HU, respectively. With regards to the chest phantom, the monitor unit (MU) difference between the treatment plan calculated using MDCT and those based on CBCT, shading corrected CBCT and VMCT was 6.32%, 1.05% and 0.94%, respectively. CONCLUSIONS: Enhancement of image quality in on-board CBCT can contribute to daily patient setup and adaptive dose delivery, thus enabling higher confidence in patient treatment accuracy in radiation therapy. Based on our results, VMCT has the highest image quality, followed by the shading corrected CBCT and the original CBCT. The research results presented in this study should be able to provide a route to reach a high level of image quality for CBCT imaging in radiation oncology. PMID- 27280598 TI - An Investigation of Sodium Fusidate and Recombinant Cytochrome P450 Enzymes Inhibition In-Vitro. AB - BACKGROUND: Sodium fusidate (fusidic acid) is an antimicrobial agent that is used in the treatment of staphylococcal and streptococcal infections. Several case reports have noted a drug interaction between sodium fusidate and CYP3A4 metabolised statins, leading to statin toxicity. It is unclear whether sodium fusidate has the potential to cause interactions with other cytochrome P450 enzymes. OBJECTIVE: To investigate the effects of sodium fusidate on recombinant cytochrome P450 enzymes (1A2, 2C9, 2C19, 2D6 and 3A4) in-vitro. METHODS: A range of sodium fusidate concentrations (0.1uM, 1uM, 10uM, 100uM, 300uM, 1000uM and 10000uM) were tested to examine its activity on rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 and rCYP3A4 using a luminescent assay with a luciferin substrate. RESULTS: Sodium fusidate inhibited all enzymes at tested concentrations which are relevant to those likely to be achieved in clinical practice. Further, sodium fusidate was found to be a time-dependent inhibitor of all the tested isoenzymes, with the exception of rCYP2C9. CONCLUSION: These findings suggest that there is a potential for sodium fusidate to cause drug interactions when used with other agents that are substrates for rCYP1A2, rCYP2C9, rCYP2C19, rCYP2D6 or rCYP3A4. Understanding the basis of this potential drug interaction will assist in safer use of sodium fusidate in clinical practice. PMID- 27280599 TI - Effect of Cardiovascular Injury on Catabolism of Adenosine and Adenosine 5 'Triphosphate in Systemic Blood in a Freely Moving Rat Model In Vivo. AB - BACKGROUND: Previous studies have shown that catabolism of adenosine 5' triphosphate (ATP) in red blood cell (RBC) may be a key factor for cardiovascular protection and maintaining cardiovascular homeostasis. OBJECTIVE: To investigate the effect of cardiovascular injury on adenosine and ATP catabolism in systemic blood using a freely moving rat model in vivo. METHOD: After acclimatized to the experimental environment, Sprague Dawley (SD) rats were each given either isoproterenol (30 mg/kg) or saline (1 mL/kg) by subcutaneous (sc) injection. Blood samples were collected sequentially for up to 6 hours for measurement of red blood cell (RBC) concentrations of adenine nucleotides and plasma concentrations of adenosine and its oxypurine metabolites. RESULTS: We have found isoproterenol induced 50% mortality under the experimental condition. Plasma concentrations of adenosine (ADO) and uric acid (UA) and red blood cell (RBC) concentrations of adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP) in RBC were significantly higher in the isoproterenol treated rats (p < 0.05 for all the comparison). On the other hand, plasma concentrations of hypoxanthine (HYP) were higher in the control group (p < 0.05), but there was no statistically significant changes in ATP concentrations in the RBC (p > 0.05). CONCLUSION: Cardiovascular injury induced by isoproterenol resulted in breakdown of ATP to ADP and AMP in the RBC and also breakdown of ADO to UA in plasma and other tissues. PMID- 27280600 TI - Genomic and transcriptomic profiles and in vitro resistance to mitoxantrone and idarubicin in pediatric acute leukemias. AB - BACKGROUND: A major problem in the treatment of leukemia is the development of drug resistance to chemotherapeutic agents. METHODS: To determine the ex vivo drug resistance profile to anthracyclines, an 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl-tetrazoliumbromide (MTT) cytotoxicity assay was performed on mononuclear cells obtained from 155 patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). Gene expression profiles (for 51 patients with ALL and 16 with AML) were prepared on the basis of cRNA hybridization to oligonucleotide arrays of the human genome (Affymetrix). Hierarchical clustering, assignment location and biological function were investigated during the correlation analysis for identified probe sets. Comparative genomic hybridization (CGH) array profiles (34 patients with ALL and 12 with AML) were prepared on the basis of DNA hybridization to oligonucleotide arrays of the human genome (Agilent). The validation of the array results was performed by a quantitative reverse transcriptase polymerase chain reaction. RESULTS: The collected expression and CGH microarray experiment results indicate that the ITGB2, SCL6A7, CASP1 and DUSP genes may comprise a resistance marker for acute leukemia cells correlated with anthracyclines. Moreover, there were also identified chromosome rearrangements associated with drug resistance, such as del5q32-35.3 and amp8p12 p11.21. Precise genes, as well as genome aberrations, might be classified as targets in therapy. CONCLUSIONS: In AML, the resistance of blasts to idarubicin and mitoxantrone may reflect an impaired integrin pathway. In ALL, the development of resistance is caused by the inhibition of B and T cell activation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27280602 TI - Correction: Accelerating Influenza Research: Vaccines, Antivirals, Immunomodulators and Monoclonal Antibodies. The Manufacture of a New Wild-Type H3N2 Virus for the Human Viral Challenge Model. AB - [This corrects the article DOI: 10.1371/journal.pone.0145902.]. PMID- 27280601 TI - Socioeconomic Inequalities in Psychological Distress among Urban Adults: The Moderating Role of Neighborhood Social Cohesion. AB - BACKGROUND: Various studies have reported socioeconomic inequalities in mental health among urban residents. This study aimed at investigating whether neighborhood social cohesion influences the associations between socio-economic factors and psychological distress. METHODS: Cross-sectional questionnaire study on a random sample of 18,173 residents aged 16 years and older from 211 neighborhoods in the four largest cities in the Netherlands. Psychological distress was the dependent variable (scale range 10-50). Neighborhood social cohesion was measured by five statements and aggregated to the neighborhood level using ecometrics methodology. Multilevel linear regression analyses were used to investigate cross-level interactions, adjusted for neighborhood deprivation, between individual characteristics and social cohesion with psychological distress. RESULTS: The mean level of psychological distress among urban residents was 17.2. Recipients of disability, social assistance or unemployment benefits reported higher psychological distress (beta = 5.6, 95%CI 5.2 to 5.9) than those in paid employment. Persons with some or great financial difficulties reported higher psychological distress (beta = 3.4, 95%CI 3.2 to 3.6) than those with little or no financial problems. Socio-demographic factors were also associated with psychological distress, albeit with much lower influence. Living in a neighborhood with high social cohesion instead of low social cohesion was associated with a lower psychological distress of 22% among recipients of disability, social assistance or unemployment benefits and of 13% among citizens with financial difficulties. CONCLUSIONS: Residing in socially cohesive neighborhoods may reduce the influence of lack of paid employment and financial difficulties on psychological distress among urban adults. Urban policies aimed at improving neighborhood social cohesion may contribute to decreasing socio economic inequalities in mental health. PMID- 27280603 TI - Standardised survey method for identifying catchment risks to water quality. AB - This paper describes the development and application of a systematic methodology to identify and quantify risks in drinking water and recreational catchments. The methodology assesses microbial and chemical contaminants from both diffuse and point sources within a catchment using Escherichia coli, protozoan pathogens and chemicals (including fuel and pesticides) as index contaminants. Hazard source information is gathered by a defined sanitary survey process involving use of a software tool which groups hazards into six types: sewage infrastructure, on-site sewage systems, industrial, stormwater, agriculture and recreational sites. The survey estimates the likelihood of the site affecting catchment water quality, and the potential consequences, enabling the calculation of risk for individual sites. These risks are integrated to calculate a cumulative risk for each sub catchment and the whole catchment. The cumulative risks process accounts for the proportion of potential input sources surveyed and for transfer of contaminants from upstream to downstream sub-catchments. The output risk matrices show the relative risk sources for each of the index contaminants, highlighting those with the greatest impact on water quality at a sub-catchment and catchment level. Verification of the sanitary survey assessments and prioritisation is achieved by comparison with water quality data and microbial source tracking. PMID- 27280604 TI - Removal of Giardia spp. and Cryptosporidium spp. from water supply with high turbidity: analytical challenges and perspectives. AB - Giardia and Cryptosporidium species are a serious problem if present in water supplies. The removal of these protozoans and the adaptation of existing protocols are essential for supplying drinking water to developing countries. Considering this, the aim of this study is to evaluate, on a bench level, the removal of Giardia spp. cysts and of Cryptosporidium spp. oocysts from water with high turbidity, using polyaluminium chloride as a coagulant. Filtration using mixed cellulose ester membranes, followed, or not, by purification through immunomagnetic separation (IMS) was used for detecting protozoans. By evaluating the adopted protocol, without using IMS, retrievals of 80% of cysts and 5% of oocysts were obtained, whereas by using IMS, recoveries of 31.5% of cysts and 5.75% of oocysts were reached. When analyzing the coagulant performance, a dosage of 65 mg L(-1) showed contamination from protozoans in all the samples of filtered water. A dosage of 25 mg L(-1) presented protozoans in 50% of the filtered water samples. The results showed an improved performance for the 25 mg L(-1) dosage; therefore, the control of coagulation and adaptation of detection protocols must be evaluated according to the features of raw water and availability of local resources. PMID- 27280605 TI - Reduction of microbial risk associated with greywater by disinfection processes for irrigation. AB - Greywater is one of the most important alternative sources for irrigation in arid and semi-arid countries. However, the health risk associated with the microbial contents of these waters limits their utilization. Many techniques have been developed and used to generate a high microbiological quality of greywater. The main problem in the treatment of greywater lies in the nature of pathogenic bacteria in terms of their ability to survive during/after the treatment process. The present review focused on the health risk associated with the presence of pathogenic bacteria in greywater and the treatment technologies used for the disinfection processes. PMID- 27280606 TI - Application of horizontal-flow anaerobic immobilized biomass reactor for bioremediation of acid mine drainage. AB - The production of low-pH effluent with sulfate and metals is one of the biggest environmental concerns in the mining industry. The biological process for sulfate reduction has the potential to become a low-cost solution that enables the recovery of interesting compounds. The present study analyzed such a process in a horizontal-flow anaerobic immobilized biomass (HAIB) reactor, employing ethanol as the carbon and energy source. Results showed that a maximal efficiency in the removal of sulfate and ethanol could only be obtained by reducing the applied sulfate load (225.1 +/- 38 g m(-3) d(-1)). This strategy led to over 75% of chemical oxygen demand (COD) and sulfate removal. Among the COD/SO4(2-) studied ratios, 0.67 showed the most promising performance. The effluent's pH has naturally remained between 6.8 and 7.0 and the complete oxidation of the organic matter has been observed. Corrections of the influent pH or effluent recirculation did not show any significant effect on the COD and sulfate removal efficiency. Species closely related to strains of Clostridium sp. and species of Acidaminobacter hydrogenomorfans and Fusibacter paucivorans that can be related to the process of sulfate reduction were found in the HAIB reactors when the initial pH was 5 and the COD/SO4(2-) ratio increased to 1.0. PMID- 27280608 TI - Disinfection of Escherichia coli and Pseudomonas aeruginosa by copper in water. AB - When households lack access to continuous piped water, water storage in the home creates opportunities for contamination. Storage in copper vessels has been shown to reduce microbes, but inactivation kinetics of enteric bacteria in water by copper alone needs to be understood. This work characterized inactivation kinetics of Escherichia coli and Pseudomonas aeruginosa by dissolved ionic copper in water. Reductions of E. coli and P. aeruginosa increase with increasing dose. At 0.3 mg/L, there was a 2.5 log10 reduction of E. coli within 6 hours. At 1 and 3 mg/L, the detection limit was reached between 3 and 6 hours; maximum reduction measured was 8.5 log10. For P. aeruginosa, at 6 hours there was 1 log10 reduction at 0.3 mg/L, 3.0 log10 at 1 mg/L, and 3.6 log10 at 3 mg/L. There was no significant decline in copper concentration. Copper inactivates bacteria under controlled conditions at doses between 0.3 and 1 mg/L. E. coli was inactivated more rapidly than P. aeruginosa. Copper at 1 mg/L can achieve 99.9% inactivation of P. aeruginosa and 99.9999997% inactivation of E. coli over 6 hours, making it a candidate treatment for stored household water. PMID- 27280609 TI - Early warning of changing drinking water quality by trend analysis. AB - Monitoring and control of water treatment plants play an essential role in ensuring high quality drinking water and avoiding health-related problems or economic losses. The most common quality variables, which can be used also for assessing the efficiency of the water treatment process, are turbidity and residual levels of coagulation and disinfection chemicals. In the present study, the trend indices are developed from scaled measurements to detect warning signs of changes in the quality variables of drinking water and some operating condition variables that strongly affect water quality. The scaling is based on monotonically increasing nonlinear functions, which are generated with generalized norms and moments. Triangular episodes are classified with the trend index and its derivative. Deviation indices are used to assess the severity of situations. The study shows the potential of the described trend analysis as a predictive monitoring tool, as it provides an advantage over the traditional manual inspection of variables by detecting changes in water quality and giving early warnings. PMID- 27280607 TI - Human infective potential of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi in urban wastewater treatment plant effluents. AB - Cryptosporidiosis, giardiasis, and microsporidiosis are important waterborne diseases. In the standard for wastewater treatment plant (WWTP) effluents in China and other countries, the fecal coliform count is the only microbial indicator, raising concerns about the potential for pathogen transmission through WWTP effluent reuse. In this study, we collected 50 effluent samples (30 L/sample) from three municipal WWTPs in Shanghai, China, and analyzed for Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi by microscopy and/or polymerase chain reaction (PCR). Moreover, propidium monoazide (PMA)-PCR was used to assess the viability of oocysts/cysts. The microscopy and PCR-positive rates for Cryptosporidium spp. were 62% and 40%, respectively. The occurrence rates of G. duodenalis were 96% by microscopy and 92-100% by PCR analysis of three genetic loci. Furthermore, E. bieneusi was detected in 70% (35/50) of samples by PCR. Altogether, 10 Cryptosporidium species or genotypes, two G. duodenalis genotypes, and 11 E. bieneusi genotypes were found, most of which were human-pathogenic. The chlorine dioxide disinfection employed in WWTP1 and WWTP3 failed to inactivate the residual pathogens; 93% of the samples from WWTP1 and 83% from WWTP3 did not meet the national standard on fecal coliform levels. Thus, urban WWTP effluents often contain residual waterborne human pathogens. PMID- 27280610 TI - Rainfall-induced release of microbes from manure: model development, parameter estimation, and uncertainty evaluation on small plots. AB - A series of simulated rainfall-runoff experiments with applications of different manure types (cattle solid pats, poultry dry litter, swine slurry) was conducted across four seasons on a field containing 36 plots (0.75 * 2 m each), resulting in 144 rainfall-runoff events. Simulating time-varying release of Escherichia coli, enterococci, and fecal coliforms from manures applied at typical agronomic rates evaluated the efficacy of the Bradford-Schijven model modified by adding terms for release efficiency and transportation loss. Two complementary, parallel approaches were used to calibrate the model and estimate microbial release parameters. The first was a four-step sequential procedure using the inverse model PEST, which provides appropriate initial parameter values. The second utilized a PEST/bootstrap procedure to estimate average parameters across plots, manure age, and microbe, and to provide parameter distributions. The experiment determined that manure age, microbe, and season had no clear relationship to the release curve. Cattle solid pats released microbes at a different, slower rate than did poultry dry litter or swine slurry, which had very similar release patterns. These findings were consistent with other published results for both bench- and field-scale, suggesting the modified Bradford-Schijven model can be applied to microbial release from manure. PMID- 27280611 TI - The South Australian Safe Drinking Water Act: summary of the first year of operation. AB - The Safe Drinking Water Act 2011 was introduced in South Australia to provide clear direction to drinking water providers on how to achieve water safety. The Act requires drinking water providers to register with SA Health and develop a risk management plan (RMP) for their water supply that includes operational and verification monitoring plans and an incident notification and communication protocol. During the first year of operation, 212 drinking water providers registered under the Act, including one major water utility and a range of small to medium sized providers in regional and remote areas of the State. Information was captured on water source(s) used and water treatment. Rainwater was the most frequently reported drinking water source (66%), followed by bore water (13%), on supply or carting of mains water (13%), mixed source (rainwater with bore water backup) (6%) and surface water (3%). The majority of providers (91%) treated the water supply, 87% used disinfection. During the first year of operation, 16 water quality incidents were formally reported to SA Health. These included both microbial and chemical incidents. Case studies presented highlight how the RMPs are assisting drinking water providers to identify incidents of potential health concern and implement corrective actions. PMID- 27280612 TI - Evaluation of potential human health risk and investigation of drinking water quality in Isparta city center (Turkey). AB - Isparta city center is selected as a work area in this study because the public believes that the tap water is dirty and harmful. In this study, the city's drinking water in the distribution system and other spring waters which are used as drinking water in this region were investigated from the point of water quality and health risk assessment. Water samples were collected from major drinking water springs, tap waters, treatment plants and dam pond in the Isparta province center. Ca-Mg-HCO3, Mg-Ca-HCO3, Ca-Na-HCO3, Ca-HCO3, Ca-HCO3-SO4 and Ca Mg-HCO3-SO4 are dominant water types. When compared to drinking water guidelines established by World Health Organization and Turkey, much greater attention should be paid to As, Br, Fe, F, NH4, PO4 through varied chemicals above the critical values. The increases of As, Fe, F, NH4 and PO4 are related to water rock interaction. In tap waters, the increases of As and Fe are due to corrosion of pipes in drinking water distribution systems. The major toxic and carcinogenic chemicals within drinking water are As and Br for both tap water and spring water. Also, F is the non-carcinogenic chemical for only spring waters in the study area. PMID- 27280613 TI - Effects of plumbing systems on human exposure to disinfection byproducts in water: a case study. AB - Disinfection byproducts (DBPs) in water distribution systems (WDS) are monitored for regulatory compliance, while populations are exposed to DBPs in tap water that may be different due to stagnation of water in plumbing pipes (PP) and heating in hot water tanks (HWT). This study investigated the effects of water stagnation in PP and HWT on exposure and risk of DBPs to humans. Trihalomethanes (THMs) in PP and HWT were observed to be 1.1-2.4 and 1.6-3.0 times, respectively, to THMs in the WDS, while haloacetic acids (HAAs) were 0.9-1.8 and 1.2-1.9 times, respectively, to HAAs in the WDS. The chronic daily intakes of DBPs from PP and HWT were 0.6-1.8 and 0.5-2.3 times the intakes from WDS. The cancer risks from PP and HWT were 1.46 (0.40-4.3) and 1.68 (0.35-5.1) times the cancer risks from WDS. The findings may assist in regulating DBPs exposure concentrations. PMID- 27280614 TI - Measuring the willingness to pay for drinking water quality improvements: results of a contingent valuation survey in Songzi, China. AB - The aim of this study is to elicit local residents' willingness to pay (WTP), by applying the contingent valuation method as a surcharge on their water bill, for a given improvement in the drinking water quality and the supply reliability. The mean WTP for the drinking water quality improvement program was estimated to be 16.71 yuan (0.3% of total household income). The results note that more educated respondents and households with higher income and with fewer household members are, on average, willing to pay more. This study also demonstrates that respondents' concerns regarding drinking water quality and perceptions of the health risk of drinking water quality can have significant positive impacts on people's WTP. The research results can help decision-makers understand the local population's demand for improved drinking water quality and undertake an environmental cost-benefit analysis. PMID- 27280615 TI - Improved water and household water purification practices among orphans and vulnerable children in a multi-sectoral empowerment program in Eastern province, Kenya. AB - Water quality is an important determinant of diarrheal illnesses, especially affecting children in sub-Saharan Africa. Orphans and vulnerable children (OVC) in sub-Saharan Africa are at increased risk of poor quality drinking water, and therefore of diarrheal illness. The present study assesses primary drinking water source and typical household water purification among OVC households involved in a multi-sectoral empowerment program in semi-rural Kenya. Findings show water purification practices, but not water source, significantly increase with more time in the program. Other factors associated with safer water include household income, orphan type, food consumption and security, school completion, psychological resilience, engaging in sexual intercourse with more than one partner in the past 12 months, and previous year's financial status. Incorporating water quality improvements in a community-based empowerment program such as the one described may be one method of improving water quality and decreasing diarrheal illnesses among OVCs in sub-Saharan Africa. PMID- 27280616 TI - Blending as the best compliance option for the management of radioactivity in drinking water supplied from the deep sandstone aquifer in Southern Jordan. AB - This paper describes management options and interventions taken by the Government of Jordan to ensure that the quality of drinking water supplied to consumers via the Disi Water Conveyance Project (DWCP) meets Jordanian drinking water standards and WHO guidelines for drinking water quality in respect of their radiological composition. Results from an initial survey of radioactivity present in water abstracted from each of the 55 wells (which comprise the operational well field) indicated an average radiological dose of 0.8 milliSieverts per year (mSv/y) would be accrued by members of the population if consuming water directly from the well head. During full scale operation, the estimated accrued dose from the well field as a whole decreased to an average of 0.7 mSv/y which was still approximately 1.4 times the Jordanian reference radiological limit for drinking water (0.5 mSv/y). Following assessment of treatment options by relevant health and water authorities, blending prior to distribution into the consumer network was identified as the most practicable remedial option. Results from monthly sampling undertaken after inline blending support the adoption of this approach, and indicate a reduction in the committed effective dose to 0.4 mSv/y, which is compliant with Jordanian standards. PMID- 27280617 TI - Results of heavy metals and other water quality levels in tap water from Can sourced from Agi Dagi (Mt. Agi) (Canakkale, Turkey). AB - In this study, the concentrations of heavy metals Pb, Cu, Zn, Cd, Ni, Fe, Mn and Cr were determined using an inductively coupled plasma and optical emission spectrophotometer (ICP-OES), and water quality parameters pH, temperature, and conductivity were measured using the YSI 556 MPS water probe. The water samples were collected monthly from five different street tap water points sourced from Mt. Agi (Agi Dagi in Turkish) spring waters between May 2012 and February 2013 in Can (Canakkale, Turkey). All results were compared with the drinking water standards of the Turkish Standards Institute (TSE 266), World Health Organization, European Union and US Environmental Protection Agency. While concentrations of Cu, Zn, Fe, and Mn were within limit values, Pb, Cd, Ni, and Cr were at undetectable limits. The highest concentrations of Cu, Zn, Fe, and Mn were 0.010 ppm, 0.018 ppm, 0.058 ppm, and 0.014 ppm, respectively. The findings revealed that although there was no public health risk in view of heavy metal concentrations, there was an acidity problem due to lower pH levels correlated with some heavy metals such as Cu (R = 0.419), Fe (R = -0.421) and Mn (R = 0.687). PMID- 27280618 TI - Neighborhood diversity of potentially pathogenic bacteria in drinking water from the city of Maroua, Cameroon. AB - This study examined the spatial variation of potential gastrointestinal pathogens within drinking water sources and home storage containers in four neighborhoods in Maroua, Cameroon. Samples were collected from source (n = 28) and home containers (n = 60) in each study neighborhood. Pathogen contamination was assessed using quantitative polymerase chain reaction, targeting Campylobacter spp., Shiga toxin producing Escherichia coli (virulence genes, stx1 and stx2), and Salmonella spp. Microbial source tracking (MST) targeted three different host specific markers: HF183 (human), Rum2Bac (ruminant) and GFD (poultry) to identify contamination sources. Staphylococcus aureus and the tetracycline-resistance gene (tetQ) were assessed to measure human hand contact and presence of antibiotic resistant bacteria. Pathogen/MST levels were compared statistically and spatially, and neighborhood variation was compared with previously collected demographic information. All the test fecal markers and pathogens (except Arcobacter) were detected in home and source samples. Two neighborhoods tested positive for most pathogens/MST while the others only tested positive for one or two. Spatial variation of pathogens/MST existed between sources, storage containers, and neighborhoods. Differing population density and ethno-economic characteristics could potentially explain variation. Future research should explore the influence of demographic and ethno-economic factors on water quality during microbial risk assessments in urban Africa. PMID- 27280619 TI - Immune Responses in U.S. Military Personnel Who Received Meningococcal Conjugate Vaccine (MenACWY) Concomitantly with Other Vaccines Were Higher than in Personnel Who Received MenACWY Alone. AB - Immunological responses to vaccination can differ depending on whether the vaccine is given alone or with other vaccines. This study was a retrospective evaluation of the immunogenicity of a tetravalent meningococcal conjugate vaccine for serogroups A, C, W, and Y (MenACWY) administered alone (n = 41) or concomitantly with other vaccines (n = 279) to U.S. military personnel (mean age, 21.6 years) entering the military between 2006 and 2008. Concomitant vaccines included tetanus/diphtheria (Td), inactivated polio vaccine (IPV), hepatitis vaccines, and various influenza vaccines, among others; two vaccine groups excluded Tdap and IPV. Immune responses were evaluated in baseline and postvaccination sera for Neisseria meningitidis serogroups C and Y 1 to 12 months (mean, 4.96 months) following vaccination. Functional antibodies were measured by using a serum bactericidal antibody assay with rabbit complement (rSBA) and by measurement of serogroup-specific immunoglobulin G (IgG) antibodies. The percentage of vaccinees reaching threshold levels (IgG concentration in serum, >=2 MUg/ml; rSBA titer, >=8) corresponding to an immunologic response was higher postvaccination than at baseline (P < 0.001). Administration of MenACWY along with other vaccines was associated with higher geometric means of IgG concentrations and rSBA titers than those measured 4.60 months after a single dose of MenACWY. In addition, higher percentages of vaccinees reached the immunological threshold (range of odds ratios [ORs], 1.5 to 21.7) and more of them seroconverted (OR range, 1.8 to 4.8) when MenACWY was administered with any other vaccine than when administered alone. Additional prospective randomized clinical trials are needed to confirm the observed differences among groups in the immune response to MenACWY when given concomitantly with other vaccines to U.S. military personnel. PMID- 27280621 TI - Comparison of Enzyme Immunoassays for Detection of Antibodies to Hepatitis D Virus in Serum. AB - Serology remains critical for diagnosing hepatitis D virus (HDV) infection, which affects 15 to 20 million people worldwide, but the literature on characterizing commercial enzyme immunoassays (EIAs) dates back to 15 years ago. We evaluated 2 commercial EIAs currently available for detecting anti-HDV antibodies. The DiaSorin assay demonstrated 100% sensitivity and specificity. Using a modified cutoff value, the Cusabio assay demonstrated a sensitivity of 81.3% and specificity of 90.9%. Our data show that recently developed EIAs are reliable for anti-HDV antibody detection. PMID- 27280620 TI - Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination. AB - Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection (n = 75), individuals with LLRs (n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals (n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs (P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C reactive protein (P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile. PMID- 27280622 TI - Monoclonal Antibodies to Shigella Lipopolysaccharide Are Useful for Vaccine Production. AB - There is a significant need for an effective multivalent Shigella vaccine that targets the most prevalent serotypes. Most Shigella vaccines under development utilize serotype-specific lipopolysaccharides (LPSs) as a major component based on protection and epidemiological data. As vaccine formulations advance from monovalent to multivalent, assays and reagents need to be developed to accurately and reproducibly quantitate the amount of LPSs from multiple serotypes in the final product. To facilitate this effort, we produced 36 hybridomas that secrete monoclonal antibodies (MAbs) against the O antigen on the LPS from Shigella flexneri 2a, Shigella flexneri 3a, and Shigella sonnei We used six of these monoclonal antibodies for an inhibition enzyme-linked immunosorbent assay (iELISA), measuring LPSs with high sensitivity and specificity. It was also demonstrated that the Shigella serotype-specific MAbs were useful for bacterial surface staining detected by flow cytometry. These MAbs are also useful for standardizing the serum bactericidal assay (SBA) for Shigella Functional assays, such as the in vitro bactericidal assay, are necessary for vaccine evaluation and may serve as immunological correlates of immunity. An S. flexneri 2a-specific monoclonal antibody killed S. flexneri 2b isolates, suggesting that S. flexneri 2a LPS may induce cross-protection against S. flexneri 2b. Overall, the Shigella LPS-specific MAbs described have potential utility to the vaccine development community for assessing multivalent vaccine composition and as a reliable control for multiple immunoassays used to assess vaccine potency. PMID- 27280624 TI - Management of Snapping Scapula Syndrome. AB - Snapping scapula syndrome is a rare condition caused by the disruption of the gliding articulation between the anterior scapula and the posterior chest wall. The etiology of snapping scapula syndrome is multifactorial, and contributing factors include scapular dyskinesis, bursitis from repetitive use or trauma, and periscapular lesions. Although the majority of cases are initially treated with nonoperative modalities, recalcitrant snapping scapula syndrome can warrant surgical management. This report describes a 34-year-old amateur weight lifter with a 1-year history of increasing pain and fullness over his posterior shoulder region. He reported full shoulder motion associated with an audible, palpable, and painful crepitus, exacerbated with overhead movement and wall pushups. Previous periscapular stabilization exercises and corticosteroid injection yielded minimal resolution of his symptoms. Prior to being referred to the authors' clinic, the patient was evaluated at an outside facility and deemed a suboptimal candidate for arthroscopic bursectomy because of the large size and location of this lesion. Magnetic resonance imaging showed a large polylobulated fluid collection causing scapulothoracic distention. There was no evidence of osseous abnormalities originating from the scapular body. Computed tomography guided placement of methylene blue and contrast dye was used to facilitate localization and, in an effort to minimize recurrence, ensure the complete removal of bursal tissue. During 8 weeks, this patient recovered unremarkably and returned to full-duty activities with resolution of symptoms. The authors present the management of chronic and recalcitrant snapping scapula syndrome, and report the open excision of the largest scapulothoracic bursal lesion described, to their knowledge, in the English literature. [Orthopedics. 2016; 39(4):e783 e786.]. PMID- 27280623 TI - Primary Osteomyelitis of the Clavicle in Children. AB - Osteomyelitis of the clavicle is a rare entity with a broad differential diagnosis and high potential for complications if not diagnosed promptly and treated appropriately. The threshold for surgical intervention should be low to prevent osteonecrosis and bony resorption. In addition, although rare, life threatening complications have been reported. This report describes primary osteomyelitis of the clavicle that was diagnosed in a 22-month-old girl on her third clinical evaluation after 4 days of symptoms. She presented to a children's tertiary care emergency department with fever and acute pain and swelling of her right shoulder and arm. The diagnosis was confirmed through clinical, laboratory, and imaging studies including ultrasound; these revealed subperiosteal abscess formation, which may have developed in part as the result of a delayed diagnosis from the 2 prior emergency department visits. The patient was treated initially with intravenous antibiotics and underwent therapeutic as well as diagnostic needle-guided tissue aspiration under ultrasound guidance. This ruled out malignancy but was not curative, and the subperiosteal abscess recurred within 24 hours, prompting formal operative irrigation and debridement. The patient was seen for 12-month follow-up and has had no complications or evidence of recurrence. This case emphasizes the need for a high index of suspicion to prevent diagnostic delays as well as the importance of a low threshold for surgical debridement to minimize the potential for complications that could prolong the treatment course. [Orthopedics. 2016; 39(4):e760-e763.]. PMID- 27280625 TI - Internal Versus External Fixation of Charcot Midfoot Deformity Realignment. AB - Internal and external fixation techniques have been described for realignment and arthrodesis of Charcot midfoot deformity. There currently is no consensus on the optimal method of surgical reconstruction. This systematic review compared the clinical results of surgical realignment with internal and external fixation, specifically in regard to return to functional ambulation, ulcer occurrence, nonunion, extremity amputation, unplanned further surgery, deep infection, wound healing problems, peri- or intraoperative fractures, and total cases with any complication. A search of multiple databases for all relevant articles published from January 1, 1990, to March 22, 2014, was performed. A logistic regression model evaluated each of the outcomes and its association with the type of fixation method. The odds of returning to functional ambulation were 25% higher for internal fixation (odds ratio [OR], 1.259). Internal fixation had a 42% reduced rate of ulcer occurrence (OR, 0.578). External fixation was 8 times more likely to develop radiographic nonunion than internal fixation (OR, 8.2). Internal fixation resulted in a 1.5-fold increase in extremity amputation (OR, 1.488), a 2-fold increase in deep infection (OR, 2.068), a 3.4-fold increase in wound healing complications (OR, 3.405), and a 1.5-fold increase in the total number of cases experiencing any complication (OR, 1.525). This was associated with a 20% increase in the need for unplanned further surgery with internal fixation (OR, 1.221). Although internal fixation may decrease the risk of nonunion and increase return to functional ambulation, it had a higher rate of overall complications than external fixation for realignment and arthrodesis of Charcot midfoot deformity. [Orthopedics. 2016; 39(4):e595-e601.]. PMID- 27280626 TI - Minimally Traumatic Spinopelvic Dissociation With Prolonged Bisphosphonate Use. AB - Bisphosphonates have become the first-line treatment for diseases involving excessive osteoclast-mediated bone resorption. However, evidence suggests that elevated doses or prolonged treatment may impair normal skeletal mineralization and may be associated with fractures. The majority of these fractures are located in the subtrochanteric region. This article presents the first described case of atraumatic spinopelvic dissociation related to a combination of osteoporosis and prolonged bisphosphonate use. The current literature also is reviewed, and putative mechanisms and management options are discussed. [Orthopedics. 2016; 39(4):e753-e755.]. PMID- 27280627 TI - Atypical Pectoralis Major Muscle Wasting in a Recreational Weight Lifter. AB - Pectoralis major injuries are relatively uncommon and can pose a diagnostic challenge. Deformity and weakness of this muscle in weight lifters is typically due to traumatic tendon rupture and often requires surgical repair. However, there are other less common etiologies that can mimic the clinical presentation of pectoralis major wasting and weakness that require different treatment approaches. This article describes a case of a 48-year-old recreational weight lifter who presented with severe pectoralis major wasting and weakness secondary to isolated mononeuropathy of the lateral pectoral nerve possibly due to Parsonage Turner syndrome. The patient was treated nonoperatively and achieved full recovery 18 months after onset. Parsonage Turner syndrome should be included in the differential diagnosis of patients with atraumatic weakness and wasting of the pectoralis major muscle and dysfunction. [Orthopedics. 2016; 39(4):e756 e759.]. PMID- 27280628 TI - Excision and Reimplantation of the Proximal Humerus After Fracture-Dislocation. AB - Fractures of the proximal humerus are common and the treatment for both displaced and comminuted variants remains controversial. Treatment options initially consisted of closed reduction, traction, casting, and abduction splints. In the early 1930s, operative treatment for displaced fractures gained popularity, which continued in the 1940s and 1950s. Humeral head replacement for severely displaced fractures of the proximal humerus was introduced in the 1950s. In the 1970s, the Association for Osteosynthesis/Association for the Study of Internal Fixation popularized plates and screws for fracture fixation, and humeral head prostheses were redesigned. The traditional management of severely displaced proximal humerus fractures has been with arthroplasty because of the significant risk of osteonecrosis of the humeral head following open reduction and internal fixation. The authors present a case of a 51-year-old right-hand-dominant man who sustained a seizure along with a posteriorly displaced proximal humerus fracture dislocation of the right upper extremity. This was treated with surgical extrusion of the entire humeral head and subsequent open reduction and internal fixation. During the surgical procedure, the patient's humeral head was completely extruded from the body through a posterior incision and then reduced back to the proximal humerus through the standard anterior deltopectoral approach. After 4 years of follow-up, the patient remains pain free, has functional range of motion, and is without signs of osteonecrosis on plain radiographs. This case illustrates that even with complete disruption of the vascular supply to the humeral head, revascularization after osteosynthesis is possible. [Orthopedics. 2016; 39(4):e779-e782.]. PMID- 27280629 TI - Resilience of Key Biological Parameters of the Senegalese Flat Sardinella to Overfishing and Climate Change. AB - The stock of the Senegalese flat sardinella, Sardinella maderensis, is highly exploited in Senegal, West Africa. Its growth and reproduction parameters are key biological indicators for improving fisheries management. This study reviewed these parameters using landing data from small-scale fisheries in Senegal and literature information dated back more than 25 years. Age was estimated using length-frequency data to calculate growth parameters and assess the growth performance index. With global climate change there has been an increase in the average sea surface temperature along the Senegalese coast but the length-weight parameters, sex ratio, size at first sexual maturity, period of reproduction and condition factor of S. maderensis have not changed significantly. The above parameters of S. maderensis have hardly changed, despite high exploitation and fluctuations in environmental conditions that affect the early development phases of small pelagic fish in West Africa. This lack of plasticity of the species regarding of the biological parameters studied should be considered when planning relevant fishery management plans. PMID- 27280630 TI - Statin use and all-cancer survival: prospective results from the Women's Health Initiative. AB - BACKGROUND: This study aims to investigate the association between statin use and all-cancer survival in a prospective cohort of postmenopausal women, using data from the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT). METHODS: The WHI study enrolled women aged 50-79 years from 1993 to 1998 at 40 US clinical centres. Among 146 326 participants with median 14.6 follow-up years, 23 067 incident cancers and 3152 cancer deaths were observed. Multivariable-adjusted Cox proportional hazards models were used to investigate the relationship between statin use and cancer survival. RESULTS: Compared with never-users, current statin use was associated with significantly lower risk of cancer death (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.71-0.86, P<0.001) and all-cause mortality (HR, 0.80; 95% CI, 0.74-0.88). Use of other lipid-lowering medications was also associated with increased cancer survival (P interaction (int)=0.57). The lower risk of cancer death was not dependent on statin potency (P-int=0.22), lipophilicity/hydrophilicity (P-int=0.43), type (P int=0.34) or duration (P-int=0.33). However, past statin users were not at lower risk of cancer death compared with never-users (HR, 1.06; 95% CI, 0.85-1.33); in addition, statin use was not associated with a reduction of overall cancer incidence despite its effect on survival (HR, 0.96; 95% CI, 0.92-1.001). CONCLUSIONS: In a cohort of postmenopausal women, regular use of statins or other lipid-lowering medications was associated with decreased cancer death, regardless of the type, duration, or potency of statin medications used. PMID- 27280631 TI - The fraction of breast cancer attributable to smoking: The Norwegian women and cancer study 1991-2012. AB - BACKGROUND: Results from several recent cohort studies on smoking and breast cancer incidence and mortality suggest that the burden of smoking on society is underestimated. We estimated the fraction of breast cancer attributable to smoking in the Norwegian Women and Cancer Study, a nationally representative prospective cohort study. METHODS: We followed 130 053 women, aged 34-70 years, who completed a baseline questionnaire between 1991 and 2007, through linkages to national registries through December 2012. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), while adjusting for confounders. Never smokers, excluding passive smokers, were used as the reference group in all main analyses. We estimated attributable fractions (AFs) % in smokers and in the population (PAFs) % with 95% CIs. RESULTS: Altogether, 4293 women developed invasive breast cancer, confirmed by histology. Compared with never active, never passive smokers, ever (former and current) smokers had an overall risk of breast cancer that was 21% higher (HR=1.21; 95% CI=1.08-1.34). For ever smokers, the AF was 17.3% (95% CI =7.4-25.4) and for the population the PAF of breast cancer was 11.9% (95% CI=5.3-18.1). For passive smokers, the PAF of breast cancer was 3.2% (95% CI=1.0-5.4). When we applied PAF estimates for ever smoking on the 2907 new breast cancer cases among Norwegian women aged 35+ at diagnosis in 2012, this yielded 345 (95% CI=154-526) breast cancer cases that could have been avoided in the absence of active smoking that year. CONCLUSIONS: In smokers, one in six and in the population, one in nine breast cancer cases could have been avoided in the absence of active smoking. Our findings support the notion that the global cancer burden due to smoking is substantially underestimated. PMID- 27280632 TI - Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed at an advanced stage, leading to a poor prognosis. Therefore, interest in the development of non-invasive biomarkers for prognostic prediction has grown rapidly. Here, we assessed the clinical implications of v-Ki-ras2 kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated circulating tumour DNA (ctDNA) as a useful surrogate biomarker in patients with resectable PDAC. METHODS: We used droplet digital polymerase chain reaction to detect rare mutant tumour-derived KRAS genes in plasma cell-free DNA (cfDNA) as ctDNA. Samples were collected from 105 patients who underwent pancreatoduodenectomy for PDAC at a single institution. Overall survival (OS) was analysed according to the presence of ctDNA. RESULTS: Among the 105 cases, ctDNA was detected in 33 (31%) plasma samples. The median OS durations were 13.6 months for patients with ctDNA (ctDNA+) and 27.6 months for patients without ctDNA. Patients who were ctDNA+ had a significantly poorer prognosis with respect to OS (P<0.0001). CONCLUSIONS: Our findings suggested that the presence of ctDNA in plasma samples could be an important and powerful predictor of poor survival in patients with PDAC. Accordingly, ctDNA detection might be a promising approach with respect to PDAC treatment. PMID- 27280633 TI - LEM domain containing 1 promotes oral squamous cell carcinoma invasion and endothelial transmigration. AB - BACKGROUND: Oral squamous cell carcinomas have high potential for locoregional invasion and nodal metastasis. Thus, early detection and elucidation of detailed molecular mechanisms of OSCCs are important. Roles of LEM domain containing 1 (LEMD1), a novel cancer-testis antigen, in OSCCs are unclear. METHODS: We performed immunohistochemical analysis of LEMD1 in 289 OSCC patients and examined functions of LEMD1 in these carcinomas. RESULTS: Immunohistochemical analysis showed that 101 patients were positive for LEMD1. LEM domain containing 1 expression levels in OSCCs significantly correlated with tumour progression (T factor and clinical stage), nodal metastasis, and poor prognosis. LEM domain containing 1 expression was an independent predictor of disease-free survival in OSCC patients. In OSCCs, LEMD1 knockdown suppressed cancer cell invasion. Moreover, downregulation of LEMD1 expression inhibited adhesion and transmigration of OSCCs and vascular or lymphatic vascular endothelial cells. CONCLUSIONS: Our findings suggest that LEMD1 is a novel tumour progressive factor and may be a useful diagnostic and therapeutic target in OSCCs. PMID- 27280634 TI - The impact of hepatic fibrosis on the incidence of liver metastasis from colorectal cancer. AB - BACKGROUND: The aim of this study was to clarify the influence of hepatic fibrosis on metachronous liver-specific recurrence in colorectal cancer (CRC) patients who underwent colorectal surgery with curative intent. Non-alcoholic steatohepatitis (NASH) is closely associated with hepatic fibrosis (HF). The number of patients who suffer from NASH is increasing because of the consumption of high-calorie diets. It remains unclear how much of an impact NASH and HF have on the development of liver metastasis in CRC. METHODS: Patients who underwent curative surgical resection for CRC between 2000 and 2011 were included in this study. We evaluated the progression of HF by the non-alcoholic fatty liver disease fibrosis score (NFS) based on preoperative blood test results, age, body mass index, and diabetes mellitus. Patients were grouped according to high (fibrotic liver; FL) or low (normal liver; NL) NFS. The influence of HF on hepatic recurrence was assessed by survival analyses. RESULTS: A total of 953 CRC patients were enrolled, comprising 293 in stage I, 327 in stage II, and 333 in stage III. The patients included were categorised as FL (77) or NL (876). The hepatic recurrence rates were 5.3% in the NL group and 10.4% in the FL group (P=0.02), whereas the overall recurrence rates were 16.0% in the NL group and 20.7% in the FL group (P=0.03). The 5-year liver-specific recurrence-free survival rate in the FL group was significantly poorer than that in the NL group (FL 89.1%, 95% confidence interval (CI) 78.4-94.7 vs NL 96.0%, 95% CI 94.3-97.2, log-rank test P<0.01). Multivariate analysis demonstrated that HF significantly promoted liver-specific recurrence compared with NL (HR=2.98, 95% CI 1.23-7.21; P=0.02). CONCLUSION: HF is a valuable prognostic factor for hepatic recurrence after curative surgical resection of CRC. PMID- 27280635 TI - Impacts of smoking on endocrine treatment response in a prospective breast cancer cohort. AB - BACKGROUND: The association between smoking and breast cancer prognosis remains unclear. The purpose of this study was to investigate whether preoperative smoking was associated with prognosis in different treatment groups. METHODS: This population-based cohort consisted of 1065 breast cancer patients without preoperative treatment included between 2002 and 2012 in Lund, Sweden. Smoking status was examined in relation to patient and tumour characteristics, and prognosis in different treatment groups. RESULTS: At the preoperative visit, 21.0% smoked. Median follow-up time was 5.1 years. Overall, in the 1016 patients included in the survival analyses, there was no significant association between smoking and risk of breast cancer events (adjusted hazard ratio (adjHR): 1.45; 95% confidence interval (CI): 0.95-2.20). For the 309 aromatase inhibitor (AI) treated patients ?50 years with oestrogen receptor-positive (ER+) tumours, smoking was associated with risk of breast cancer events (adjHR: 2.97; 95% CI: 1.44-6.13), distant metastasis (adjHR: 4.19; 95% CI: 1.81-9.72), and death (adjHR: 3.52; 95% CI: 1.59-7.81). Smoking was not associated with breast cancer events or distant metastasis in other treatment groups. CONCLUSIONS: Preoperative smoking was only associated with an increased risk for breast cancer events and distant metastasis in AI-treated patients. If confirmed, smoking status should be taken into consideration when selecting an endocrine therapy. PMID- 27280636 TI - Expression of phosphorylated eIF4E-binding protein 1, but not of eIF4E itself, predicts survival in male breast cancer. AB - BACKGROUND: Male breast cancer is rare and treatment is based on data from females. High expression/activity of eukaryotic initiation factor 4E (eIF4E) denotes a poor prognosis in female breast cancer, and the eIF4E pathway has been targeted therapeutically. Eukaryotic initiation factor 4E activity in female breast cancer is deregulated by eIF4E overexpression and by phosphorylation of its binding protein, 4E-BP1, which relieves inhibitory association between eIF4E and 4E-BP1. The relevance of the eIF4E pathway in male breast cancer is unknown. METHODS: We have assessed expression levels of eIF4E, 4E-BP1, 4E-BP2 and phosphorylated 4E-BP1 (p4E-BP1) using immunohistochemistry in a large cohort of male breast cancers (n=337) and have examined correlations with prognostic factors and survival. RESULTS: Neither eIF4E expression nor estimated eIF4E activity were associated with prognosis. However, a highly significant correlation was found between p4E-BP1 expression and disease-free survival (DFS), linking any detectable p4E-BP1 with poor survival (univariate log rank P=0.001; multivariate HR 8.8, P=0.0001). CONCLUSIONS: Our data provide no support for direct therapeutic targeting of eIF4E in male breast cancer, unlike in females. However, as p4E-BP1 gives powerful prognostic insights that are unrelated to eIF4E function, p4E-BP1 may identify male breast cancers potentially suitable for therapies directed at the upstream kinase, mTOR. PMID- 27280637 TI - Nut consumption and prostate cancer risk and mortality. AB - BACKGROUND: Little is known of the association between nut consumption, and prostate cancer (PCa) incidence and survivorship. METHODS: We conducted an incidence analysis and a case-only survival analysis in the Health Professionals Follow-up Study on the associations of nut consumption (updated every 4 years) with PCa diagnosis, and PCa-specific and overall mortality. RESULTS: In 26 years, 6810 incident PCa cases were identified from 47 299 men. There was no association between nut consumption and being diagnosed with PCa or PCa-specific mortality. However, patients who consumed nuts five or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month (HR=0.66, 95% CI: 0.52-0.83, P-trend=0.0005). CONCLUSIONS: There were no statistically significant associations between nut consumption, and PCa incidence or PCa-specific mortality. Frequent nut consumption after diagnosis was associated with significantly reduced overall mortality. PMID- 27280638 TI - Ethnic differences in cancer symptom awareness and barriers to seeking medical help in England. AB - BACKGROUND: Ethnic differences in cancer symptom awareness and barriers to seeking medical help in the English population are not fully understood. We aimed to quantify these differences, to help develop more effective health campaigns, tailored to the needs of different ethnic groups. METHODS: Using a large national data set (n=38 492) of cross-sectional surveys that used the Cancer Research UK Cancer Awareness Measure, we examined how cancer symptom awareness and barriers varied by ethnicity, controlling for socio-economic position, age and gender. Data were analysed using multivariable logistic regression. RESULTS: Awareness of cancer symptoms was lower in minority ethnic groups than White participants, with the lowest awareness observed among Bangladeshis and Black Africans. Ethnic minorities were more likely than White British to report barriers to help seeking. South Asians reported the highest emotional barriers, such as lack of confidence to talk to the doctor, and practical barriers, such as worry about many other things. The Irish were more likely than the White British to report practical barriers, such as being too busy to visit a doctor. White British participants were more likely than any other ethnic group to report that they would feel worried about wasting the doctor's time. Overall, Black Africans had the lowest barriers. All differences were statistically significant (P<0.01 level), after controlling for confounders. CONCLUSIONS: Our findings suggest the need for culturally sensitive and targeted health campaigns, focused on improving recognition of cancer symptoms among ethnic minorities. Campaigns should tackle the specific barriers prevalent in each ethnic group. PMID- 27280640 TI - Relating minimum toe clearance to prospective, self-reported, trip-related stumbles in the community. AB - BACKGROUND: Individuals with transtibial amputation are at increase risk of falling. The absence of an ankle joint and the associated musculature in these individuals can reduce clearance between the prosthetic foot and ground during the swing phase of gait, which may increase the risk of stumbling and in turn falling. OBJECTIVES: To associate minimum toe clearance during gait in the laboratory with community-based, trip-related stumbles by individuals with transtibial amputation using conventional feet. STUDY DESIGN: Prospective cohort design; following quantitative gait analysis, participants completed electronic surveys to prospectively report stumbles and falls for 1 year thereafter. METHODS: General community with gait analysis conducted within a motion analysis laboratory and prospective tracking of stumbles occurring in the community. A volunteer sample of eight unilateral, transtibial amputees that were K3 or K4 level ambulators and current patients at a local prosthetic clinic. All participants completed the entire 1-year follow-up study. Prosthetic-side minimum toe clearance while walking on a level treadmill at self-selected speed and self reported trip-related stumbles in the community. Minimum toe clearance was defined as a local minimum of the vertical displacement of the toe from toe-off to heelstrike relative to its position during midstance. RESULTS: Prosthetic-side minimum toe clearance was more than 50% lower for participants who reported one or more trip-related stumbles on that side compared with participants who reported zero trip-related stumbles on the prosthetic side (minimum toe clearance = 12.3 +/- 0.8 mm vs 25.6 +/- 5.4 mm, respectively; p = 0.036). CONCLUSION: This is the first study relating laboratory-based measures to prospective stumbles by prosthesis users. The results suggest that prosthesis users with low minimum toe clearance may be at increased risk of experiencing a trip-related stumble in the community. Given that frequent stumbling increases the risk of falling, future work is warranted on the effectiveness of interventions focused on minimum toe clearance on reducing fall risk. Clinical relevance Interventions to increase minimum toes clearance, which could include prescription of active dorsiflexing prostheses or gait training, may help reduce the risk of trip-related falls for individuals who report a history of trip-related stumbles. PMID- 27280639 TI - Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution. AB - Envenomation of humans by snakes is a complex and continuously evolving medical emergency, and treatment is made that much more difficult by the diverse biochemical composition of many venoms. Venomous snakes and their venoms also provide models for the study of molecular evolutionary processes leading to adaptation and genotype-phenotype relationships. To compare venom complexity and protein sequences, venom gland transcriptomes are assembled, which usually requires the sacrifice of snakes for tissue. However, toxin transcripts are also present in venoms, offering the possibility of obtaining cDNA sequences directly from venom. This study provides evidence that unknown full-length venom protein transcripts can be obtained from the venoms of multiple species from all major venomous snake families. These unknown venom protein cDNAs are obtained by the use of primers designed from conserved signal peptide sequences within each venom protein superfamily. This technique was used to assemble a partial venom gland transcriptome for the Middle American Rattlesnake (Crotalus simus tzabcan) by amplifying sequences for phospholipases A2, serine proteases, C-lectins, and metalloproteinases from within venom. Phospholipase A2 sequences were also recovered from the venoms of several rattlesnakes and an elapid snake (Pseudechis porphyriacus), and three-finger toxin sequences were recovered from multiple rear fanged snake species, demonstrating that the three major clades of advanced snakes (Elapidae, Viperidae, Colubridae) have stable mRNA present in their venoms. These cDNA sequences from venom were then used to explore potential activities derived from protein sequence similarities and evolutionary histories within these large multigene superfamilies. Venom-derived sequences can also be used to aid in characterizing venoms that lack proteomic profiles and identify sequence characteristics indicating specific envenomation profiles. This approach, requiring only venom, provides access to cDNA sequences in the absence of living specimens, even from commercial venom sources, to evaluate important regional differences in venom composition and to study snake venom protein evolution. PMID- 27280641 TI - Communication techniques for improved acceptance and adherence with therapeutic footwear. AB - BACKGROUND AND AIM: Clients' acceptance and adherence with orthoses can be influenced by a clinician's communication skills. In this clinical note, we describe two communication techniques, in the context of therapeutic footwear. TECHNIQUE: Person-centred communication involves engaging with and listening to the attitudes of the client towards their condition, as well as discussing acceptance and expectations, in a structured consultation. Building a relationship is crucial and requires clients to feel heard and understood. An important influence on the acceptance and adherence is that a client makes a conscious decision to receive their device. This active receipt can be facilitated through shared decision making, wherein clinicians give clear, relevant and meaningful examples, based on clinical evidence, and ensure this is understood. DISCUSSION: Two communication techniques for clinicians providing therapeutic footwear are described. These can be adapted for use with provision of other assistive technologies to improve client acceptance and adherence. Clinical relevance Small changes in how clinicians communicate to their clients in daily practice can have a big influence on the subsequent acceptance and adherence with therapeutic footwear and indeed other prescribed assistive technologies. PMID- 27280642 TI - Photonic Torque Microscopy of the Nonconservative Force Field for Optically Trapped Silicon Nanowires. AB - We measure, by photonic torque microscopy, the nonconservative rotational motion arising from the transverse components of the radiation pressure on optically trapped, ultrathin silicon nanowires. Unlike spherical particles, we find that nonconservative effects have a significant influence on the nanowire dynamics in the trap. We show that the extreme shape of the trapped nanowires yields a transverse component of the radiation pressure that results in an orbital rotation of the nanowire about the trap axis. We study the resulting motion as a function of optical power and nanowire length, discussing its size-scaling behavior. These shape-dependent nonconservative effects have implications for optical force calibration and optomechanics with levitated nonspherical particles. PMID- 27280643 TI - Life Cycle of Peanut (Arachis hypogaea L.) Plant in Vitro. AB - Alteration of generations in peanut plants was examined by the culturing of seeds. Flowers were induced in more than 50% of the seed cultures in vitro. Benzyl aminopurine stimulated the rate of flower induction most among the factors examined. Development of pegs was stimulated by gibberellic acid given after flowering. Dark culture allowed the development of ovaries in pegs to immature seeds and then to mature seeds; with this, the life cycle of the peanut plant was complete. Mature seeds excised from the original cultures germinated normally in vitro, and the cotyledonary nodes proliferated multiple shoots on shoot-forming medium. Alteration of generations and the in vitro omission of certain steps of the life cycle in plants are discussed. PMID- 27280644 TI - Purification and Properties of Acid Stable Xylanases from Aspergillus kawachii. AB - Five extracellular endo-xylanases were recognized in the culture broth of shochu koji mold (Aspergillus kawachii, IFO 4308), and three major xylanases (XylA, XylB, and XylC) were purified and characterized. The molecular masses of XylA, XylB, and XylC were 35,000, 26,000, and 29,000, and isoelectric points were pH 6.7, 4.4, and 3.5, respectively. Amino acid compositions and other properties were studied and these three xylanases were found to be greatly different in their properties. These three xylanases, XylA, XylB, and XylC, were stable between pH 3-10, 3-10, and 1-9 and the optimum pHs were 5.5, 4.5, and 2.0, respectively. Consequently, these xylanases were acid stable xylanases, especially XylC was an acidophilic xylanase (acid xylanase). These xylanases produced various xylooligosaccharides including xylose from xylan and the main product was xylobiose in all xylanases. The production of acid xylanase (XylC) was enhanced with a low initial pH of the medium. PMID- 27280645 TI - Beneficial Effect of Dietary Fiber on the Upper Gastrointestinal Transit Time in Rats Suffering from a Toxic Dose of Amaranth. AB - Gobo dietary fiber (GDF) obtained from the roots of edible burdock (Arctium lappa L.) was examined for its protective role against amaranth (Food Red No. 2, Am) toxicity in the upper gastrointestinal tract (from the mouth to the ileal end) of rats. Ileorectostomized rats were examined for their growth response to feeding with a purified basal diet containing 4% Am with or without 7.5% GDF. The transit half-time (TT50) through the upper gastrointestinal tract was also examined with ileostomized rats by recovering the small intestinal contents from the ileal end, using Cr-EDTA as a nonabsorbable water-soluble marker. Although feeding Am to the ileorectostomized rats resulted in a 50% mortality, concurrent feeding of Am and GDF not only protected the rats from death but also significantly promoted their growth rate when compared to the effect on the survivors fed only with the Am containing diet. The results of TT50 measurements on ileostomized rats showed that the TT50 was decreased by half in the presence of Am, but was restored to the value for the control without Am when the Am-containing diet was supplemented with GDF. These and previous rsults imply that Am toxicity develops mainly in the upper gastrointestinal tract as a result of decreased availability of nutrients that is produced by the rapid transit and inhibitory effect of Am on the digestion-absorption process. The beneficial effect of GDF appears to be in normalizing the rapid transit through the upper gastrointestinal tract of chyme containing Am and not in the cecum or colon. PMID- 27280646 TI - Oxidative Stability of Sardine Oil Embedded in Spray-dried Egg White Powder and Its Use for n-3 Unsaturated Fatty Acid Fortification of Cookies. AB - Fine droplets of sardine oil either embedded in or covered with egg white powder, which had been prepared from an oil-in-water emulsion containing 10% protein-oil (9:1) mixture by spray-drying and freeze-drying, were examined for their oxidative stability during storage under moderate conditions (RH = 45-55%, 40 degrees C). The antioxidative effect was estimated by measuring the peroxide value as well as the residual unsaturated fatty acid (mainly eicosapentaenoic and docosahexaenoic acids). Microencapsulation of the oil droplets with albumen by freeze-drying was not so effective in stabilizing against oxidation as that by spray-drying, probably because of the porosity of a protein coating on oil or leakage of oil through crevices. As a practical application of powdered sardine oil (i.e., entrapped in spray-dried albumen particles), plain cookies and those enriched with the oil were baked, and any difference in taste between them was evaluated by a paired preference test assessed by 32 amateur panelists. Sardine oil fortification of the cookies was judged not to affect their quality from the results of the sensory test. Spray-dried egg white powder inclusive of sardine oil was stable during prolonged storage, so that its use would be favorable for supplying an n-3 series of polyunsaturated fatty acids. PMID- 27280647 TI - Identification of a Novel Gibberellin (GA85) in Very Young Seedlings of Brassica campestris cv. Tobin. AB - A new gibberellin (GA) was identified from extracts of cotyledons of 7 day-old canola seedlings (Brassica campestris cv. Tobin). This GA is 12alpha-hydroxy-GA1 and has been assigned the trivial name of GA85. Isolation was monitored by the Tan-ginbozu dwarf rice micro-drop assay after each high-performance liquid chromatography (HPLC) step. Identification was based on Kovats retention index (KRI) and the mass spectrum of the methyl ester, trimethylsilyl ether (MeTMSi) derivative after analysis by gas chromatography-mass spectrometry (GC-MS) in comparison with an authentic sample of 12alpha-hydroxy-GA1. Based on quantitation by the dwarf rice micro-drop assay, GA85 is one of the major biologically active GAs in cotyledons of young canola seedlings. PMID- 27280648 TI - Functional Casein-Poly saccharide Conjugates Prepared by Controlled Dry Heating. AB - Casein was conjugated with dextran and galactomannan in a controlled dry state at a relative humidity of 79% and at 60 degrees C for 24 hr. The covalent attachment of polysaccharides to casein was confirmed by SDS-PAGE and HPLC. The emulsifying activity of the casein-dextran and casein-galactomannan conjugates was 1.5 times higher than that of casein. The emulsion stability of the casein-dextran and casein-galactomannan conjugates was 10 times higher than that of casein. The improvement in these emulsifying properties reached a steady state when the conjugation of casein with polysaccharide was done for 24 hr in a controlled dry state, suggesting the rapid formation of conjugates through a Maillard reaction in the case of casein. Compared to commercial emulsifiers, the casein polysaccharide conjugates showed better emulsifying properties in acidic and high salt concentration systems. PMID- 27280649 TI - Identification and Characteristics of Lactic Acid Bacteria Isolated from Sour Dough Sponges. AB - Lactic acid bacteria in four samples of sour dough sponges were studied quantitatively and qualitatively. In each sponge, there were one or two species of the genus Lactobacillus: L. reuteri and L. curvatus in San Francisco sour dough sponge, L. brevis and L. hilgardii in panettone sour dough sponge produced in Italy, L. sanfrancisco from a rye sour dough sponge produced in Germany, and L. casei and L. curvatus from a rye sour dough sponge produced in Switzerland. For all isolates except the L. reuteri strains oleic acid, a component of the Tween 80 added to the medium, was essential for growth. It was of interest that lactobacilli requiring oleic acid were the predominant flora of lactic acid bacteria in the microbial environment of sour dough sponges. PMID- 27280650 TI - Short-term Effects of Ethanol Intoxication on Ascorbic Acid and Lipid Metabolism and on Drug-metabolizing Enzymes in Liver of Rats. AB - The effects of one-time ethanol intoxication on ascorbic acid and lipid metabolism and on drug-metabolizing enzymes in liver of rats were investigated. Male Donryu rats that had been fed semi-purified feed were given 5 g/kg ethanol solution (25%, w/v) via a stomach tube and killed 16 h after intubation. The amount of ascorbic acid excreted in the urine after ethanol administration increased, but renal and adrenal concentrations of ascorbic acid decreased. The serum levels of total cholesterol, high-density-lipoprotein cholesterol, triglycerides, phospholipids, and non-esterified fatty acids were elevated in rats given ethanol, but hepatic level of total lipids, cholesterol, triglycerides, phospholipids were not. The hepatic concentrations of cytochrome P 450 and cytochrome b5 did not increase, but this large dose of ethanol increased the activities of aminopyrine N-demethylase and cytochrome c reductase. These results indicated that the single dose of ethanol affected the ascorbic acid and lipid metabolism of rats, and induced drug-metabolizing enzymes in their liver. PMID- 27280651 TI - Enzymatic Synthesis of 5-Methyluridine from Adenosine and Thymine with High Efficiency. AB - 5-Methyluridine (5MU) was synthesized efficiently from adenosine, thymine, and phosphate by a combination of adenosine deaminase (ADA), purine nucleoside phosphorylase (PUNP), pyrimidine nucleoside phosphorylase (PYNP), and xanthine oxidase (XOD). Adenosine was converted into inosine first by ADA. 5MU and hypoxanthine were synthesized from inosine and thymine by PUNP and PYNP. The hypoxanthine formed was converted into urate via xanthine by XOD. After inosine was completely consumed, an equilibrium state, in which 5MU, thymine, ribose-1 phosphate, and phosphate were involved, was achieved. At the equilibrium state, the maximum yield of 5MU was obtained. The yield of 5MU was 74%, when the initial concentrations of adenosine, thymine, and phosphate were 5 mM each. On the other hand, in the absence of ADA or XOD the yield of 5MU was 1.8%. Several kinds of nucleosides were also synthesized with high yield by the same method. PMID- 27280652 TI - In Vivo Effects of Tea Polyphenol Intake on Human Intestinal Microflora and Metabolism. AB - Effects of tea polyphenol intake (0.4 g/volunteer, 3 times per day, for four weeks) on fecal microflora, bacterial metabolites, and pH were investigated using eight healthy human volunteers. Counts for Clostridium perfringens and other Clostridium spp. were significantly decreased during the tea polyphenol intake periods. Percentage of volunteers having C. perfringens in their feces decreased significantly, but not for other Clostridium spp. Percentage of Bifidobacterium spp. (the acid forming bacteria) in total counts and the content of volatile fatty acids including acetic and propionic acids increased significantly, which might have reduced the fecal pH. However, the tea polyphenols had no effect on fecal enzyme activities, ammonia, or putrefactive products. Two weeks after discontinuing the intake, the microflora counts and their biological parameters appeared to have returned to normal. PMID- 27280653 TI - Preventive Effect of Green Tea Polyphenols against Dental Caries in Conventional Rats. AB - The effects of green tea polyphenols, inhibitors of various biological activities of cariogenic bacteria in vitro, on caries development were examined using conventional rats. A total of 96 male rats were divided into 8 groups and the rats in the test groups were given tea polyphenols ranging from 0.1% to 0.5% in their cariogenic diet or drinking water for 40 days. Total fissure caries lesions was significantly reduced by the addition of tea polyphenols to the diet or in the drinking water. Diet containing 0.1% tea polyphenols demonstrated about 40% reduction of total fissure caries lesions. No toxic effect of tea polyphenols on rats were observed under these experimental conditions. PMID- 27280654 TI - Effects of Potassium Chloride and Sodium Chloride on the Thermal Properties of Gellan Gum Gels. AB - The exothermic and endothermic peaks in cooling and heating curves of differential scanning calorimetry (DSC) for gellan gum gels without and with potassium chloride and sodium chloride were analyzed. The gelling and melting temperatures shifted to higher temperatures with increasing gellan and salt concentration in the concentration range of gellan from 0.3 to 2.0% (w/w). The exothermic and endothermic enthalpy increased with increasing gellan and salt concentrations. Cooling DSC curves showed one exothermic peak for samples with salts and at low gellan concentration. Heating DSC curves showed many peaks for all samples except 0.3% (w/w) gellan gum gels. The sol-gel transition of samples was examined numerically by using a zipper model approach. The introduction of cations increases the number of junction zones or zippers and decreases the rotational freedom of parallel links. This makes the structure of junction zones more heat resistant, and increases the elastic modulus of the gel. PMID- 27280655 TI - A Simple Fluorometry of Hydroperoxides in Oils and Foods. AB - A fluorometry of hydroperoxides in oil and food samples was developed using diphenyl-1-pyrenylphosphine (DPPP) with a sample size of less than 20 mg by a batch method. The sensitivity was more than 10,000 times that of the conventional iodometry. A good accordance was obtained between peroxide values (POV) measured this way and by iodometry (r = 0.9995, n = 41, POV = 0.04-240). PMID- 27280657 TI - Photochemical Reaction of Perillaldehyde under Various Conditions. AB - (-)-PeriIlaldehyde (1) was photoirradiated by a 400 W high-pressure mercury lamp under various conditions. In MeOH, 1 was degraded to give two new MeOH adducts (2 and 3) and a new methyl ether (4) under an N2 stream, while 1 was converted to a dimethyl acetal (5) and oxidation product (6) in addition to 2 and 3 under an 02 stream. In EtOAc, 1 disappeared to afford two new dimers (7 and 8) under an N2 stream, while 1 was changed to two oxygenated products (9 and 10) including a new compound under an O2 stream. In the presence of rose bengal (RB), 1 was converted to 5 by visible light in MeOH under an N2 stream. Photosensitization of RB was observed under an O2 stream, and two new oxygenated products (11 and 12) were formed. Perillaldehyde was relatively stable in n-hexane under an N2 stream or in the presence of RB under an O2 stream. PMID- 27280656 TI - Purification and Some Properties of a New Levanase from Bacillus sp. No. 71. AB - A levanase from Bacillus sp. was purified to a homogeneous state. The enzyme had a molecular weight of 135,000 and an isoelectric point of pH 4.7. The enzyme was most active at pH 6.0 and 40 degrees C, stable from pH 6.0 to 10.0 for 20 hr of incubation at 4 degrees C and up to 30 degrees C for 30 min of incubation at pH 6.0. The enzyme activity was inhibited by Ag (+), Hg(2 +), Cu(2 +), Fe(3 +), Pb(2+), and p-chloromercuribenzoic acid. The enzyme hydrolyzed levan and phlein endowise to produce levanheptaose as a main product. The limit of hydrolysis of levan and phlein were 71% and 96%, respectively. PMID- 27280658 TI - New Selective Grass Herbicides and Their Hydrolytic Properties as Pro-herbicides. AB - New derivatives of pyridinyloxyphenoxypropionic acid were synthesizd, which have a keto group in their ester-alkyl structures. Some acylmethyl esters, e.g., acetylmethyl ester, hydroxyacetylmethyl ester and diazoacetylmethyl ester, were found to show outstanding herbicidal activity against grass weeds. A study of the hydrolysis rate of esters with regard to their pro-herbicide action is also discussed. PMID- 27280659 TI - Synthesis of New Abscisic Acid (ABA) Analogs Possessing a Geometrically Rigid Cyclized Side Chain. AB - In a solution, cis-abscisic acid (ABA) isomerizes into the trans-isomer which is physiologically inactive, and this structural instability is regarded as a reason for insuitability of ABA in agricultural applications. The side chain of ABA, the 2-cis-4-trans-3-methyl-2,4-pentadienoic acid moiety, was replaced with various substituted phenyl groups to examine biological effects of the inflexibility of the part. Construction of the phenyl moiety was achieved by cyclizing the ionone derivatives and subsequent aromatization. Some of those new compounds showed ABA like activity in both seed germination and transpiration assays. PMID- 27280660 TI - Syntheses of 2-Substituted 6/7-Methoxy-l,4-benzodioxan-7/6-carbaldehydes. AB - Five 2-substituted 6/7-methoxy-l,4-benzodioxan-7/6-carbaldehydes and 6-methoxy l,4-benzodioxan-7-carbaldehyde available for the syntheses of insecticidal neolignan analogs were prepared from 4/3-benzyloxy-3/4-hydroxybenzaldehydes and l,4-benzodioxan-6-carbaldehyde, respectively. PMID- 27280661 TI - Properties of a Highly Viscous Polysaccharide Produced by a Bacillus Strain Isolated from Soil. AB - Chemical and Theological properties of a highly viscous and acidic polysaccharide produced by a soil bacterium identified as Bacillus circulans are described. The molecular weight of the native polysaccharide was about 116 * 10(4) by gel filtration with HPLC. The molar ratio of D-galactose, n-mannose, and L-rhamnose contained in the polysaccharide as neutral sugar components was 1.3:1:2. The viscosity of 1% solution of the polysaccharide was about 5000 cp, which was higher than that of guar gum, a seed polysaccharide, used as a reference standard. The viscosity was affected by the pH of the polysaccharide solution, a maximum viscosity being observed at pH 5.5 for native and decationized polysaccharide solution. The viscosity of 0.3% solution was decreased to about 70% by heating at 100 degrees C and 22% at 120 degrees C for 30 min as compared to the viscosity before heating. The addition of sugars, especially sucrose and glucose, at 10-30% concentration brought about a 130-180% increase of the viscosity. The addition of CaCl2 at a low concentration markedly increased the viscosity, and a maximum viscosity was attained at 2% concentration of the salt. PMID- 27280662 TI - Role of Glutathione in the Accumulation of Potassium Ions in Escherichia coli under Osmotic Stress. AB - When Escherichia coli cells were stressed by NaCl, cellular levels of glutathione (GSH) increased, and potassium ions (K(+)) accumulated. To identify the role of the stress-induced synthesis of GSH in the accumulation of K(+), a GSH-deficient mutant of E. coli was used. The mutant grew even in a medium with a low concentration of K(+) after a lag of about 32 hr. In such cells grown under osmotic stress in this medium, K(+) did not accumulate in the lag phase. In the logarithmic phase, however, intracellular levels of K(+) increased in spite of the lack of intracellular GSH. In a medium with the usual K(+) concentration, K(+) accumulated in a pattern similar to that of the parent strain in both phases. These results showed that GSH participates in the accumulation of K(+) in cells under osmotic stress only in the lag phase in medium with little K(+). PMID- 27280663 TI - Metabolic Fate of beta-Aspartyl-(14)C-glycine in Normal Young Rats. AB - The metabolic fate of alpha- and beta-L-aspartyl-[U-(14)C]glycine was investigated in normal young rats in vivo and in vitro. The radioactive dipeptides were synthesized from L-aspartic acid and [U-(14)C]glycine in our laboratory. When labeled beta-aspartylglycine was given intraperitoneally, about 66% of the dose was excreted in the urine and 8% was recovered in the expired carbon dioxide over a 24-hr period. More than 90% of the urinary radioactivity was present in the beta-aspartylglycine fraction of the urine. When the labeled alpha-aspartylglycine was given, 3% and 22% of the dose were recovered, respectively, in the urine and expired carbon dioxide. In slice experiments with kidney, liver and small intestine from normal rats, alpha-aspartylglycine was rapidly and almost completely hydrolyzed, and a large amount of free (14)C glycine was released. In contrast, beta-aspartylglycine was hardly hydrolyzed to the corresponding amino acids in liver and small intestine, and only slightly in kidney. These results suggest that in normal young rats most beta aspartylglycine, which may originate from endogenous tissue proteins, is hardly hydrolyzed and rapidly excreted into the urine. PMID- 27280664 TI - Plasmid-associated Bacteriocin Production by and Immunity of Lactobacillus acidophilus TK8912. AB - Lactobacillus acidophilus TK8912 produces an antibacterial substance, designated acidocin 8912, which is active against strains of Lactobacillus and Lactococcus. Of all conditions tested, the production of acidocin 8912 was maximum at 30 degrees C in MRS broth. Acidocin 8912 was stable to heat treatment (120 degrees C for 20min), but completely inactivated by protease treatment. Curing a plasmid pLA103 resulted in the loss of both acidocin 8912 production (Acd(+)) and host immunity (Acd(r)). A plasmid-cured strain, TK1-4 (Acd(-) Acd(8)), was transformed to Acd(+)Acd(r) with the pLA103 plasmid. These results provided the first direct evidence in lactobacilli for involvement of this plasmid in bacteriocin production and immunity. PMID- 27280665 TI - Phosphorolytic Reaction of Cellvibrio gilvus Cellobiose Phosphorylase. AB - Cellobiose phosphorylase was purified from Cellvibrio gilvus cells by the method reported previously with some modifications, and its kinetic properties were studied in detail. The initial velocity of the synthetic reaction was 1.4 times as fast as that of the phosphorolytic one. The equilibrium constant of the phosphorolysis was 0.32 at 37 degrees C and pH 7.0. No D-[U-(14)C]glucose exchange reaction was observed in the absence of Pi. Kinetic studies on the phosphorolytic reaction showed that the reaction follows an ordered bi bi mechanism. These results make a sharp contrast to those of sucrose phosphorylase, which catalyzes fructose exchange reaction and follows a ping pong bi bi mechanism. Kinetic parameters were calculated as KmA = 2.6 mM, KmB = 0.61mM, and KiA = 6.8 mw (A, D-cellobiose; B, Pi). PMID- 27280666 TI - Lipid Accumulation in the Liver of Rats Fed a Soy Protein Isolate Diet with Excess Cystine, and its Prevention by Methionine or Choline. AB - The effects on liver and serum lipids of rats of excess cystine added to their casein or soy protein isolate diets were studied. When excess cystine was added to the casein diet, liver lipids were not changed. Using soy protein isolate as a protein source, both food consumption and body weight gain were depressed with increasing levels of dietary cystine. Liver total lipids, cholesterol, triacylglycerols, and phospholipids were increased in rats with 2.5% or 3.5% cystine diets. Serum cholesterol of rats on the 3.5% cystine diet was significantly higher than those of the other groups, which yielded similar values. Serum triacylglycerols were increased by the addition of 0.5% or 1.5% cystine, and decreased by the addition of 2.5% or 3.5% cystine to the diet. Serum free fatty acids increased or tended to increase when liver lipid accumulation was observed. The addition of either methionine or choline to the cystine-excess diet containing soy protein isolate prevented the accumulation of triacylglycerols and phospholipids in the liver although serum triacylglycerols did not return to the levels of rats on the diet without cystine, and serum free fatty acid levels were not changed. Thus, it is surmised that this fatty liver might be due to the choline deficiency induced by the excess cystine. PMID- 27280667 TI - Purification and Some Characteristics of Extracellular Lipase from Fusarium oxysporum f. sp. lini. AB - An extracellular lipase was isolated from a culture filtrate of Fusarium oxysporum f. sp. lini SUF 402 by hydrophobic chromatography. Purity of the preparation was 38-fold and recovery yield was 32%. The molecular mass of the isolated enzyme was 30 kDa. The lipase had a sugar chain, and the N-terminal amino acid was modified. The optimun pH at 37 degrees C was 7.0. The enzyme had higher activity toward p-nitrophenyl esters with long and middle chain fatty acids (C8-C18) than with a short chain fatty acid (C4). The enzyme was not inhibited by phenylmethylsulfonyl fluoride or 2-mercaptoethanol. In the case of the lipase, both the hydrolysis rate of tristearin and final concentration of fatty acid content were higher than those of triolein. The lipase was examined with respect to its ability of concentrating the n-3 polyunsaturated fatty acid (n-3 PUFA) content of partially hydrolyzed glycerides (TG and DG) obtained from two kinds of fish oil (cod liver oil and refined sardine oil). The lipase gave increases in n-3 PUFA contents as the hydrolysis progressed. The lipase concentrated only docosahexaenoic acid with little increase in icosapentaenoic acid. Maximal total n-3 PUFA contents were about 30% in both fish oils. PMID- 27280668 TI - Difference in Tryptophan-nicotinamide Conversion According to Dietary Nitrogen Sources; Casein, Casein Hydrolysate, and Mixtures of Amino Acids. AB - We investigated whether the fate of tryptophan (Trp) to nicotinamide (Nam) is changeable according to nitrogen sources or not. Male rats were fed with a nicotinic acid-free diet (Trp content was arranged at about 234mg/100g of diet) containing casein, casein hydrolysates, or mixtures of amino acids (simulating the amino acid pattern of casein) for 12 days. From the urinary excretion of Nam and its metabolites, the conversion ratio was calculated. The conversion ratio was lower in the groups fed with the casein hydrolysate diets than in the groups fed with the casein and amino acid diets. In order to find the reason, the urinary excretion of kynurenic acid, xanthurenic acid, anthranilic acid, and 3 hydroxyanthranilic acid from the upper part of the Trp-Nam conversion pathway, the contents of free Trp in whole blood, and eight kinds of enzyme activities involved in the Trp-Nam pathway were measured. From these results, it is considered that the reason why the conversion ratio was lower in the casein hydrolysate group is due to the lower concentration of free Trp in whole blood and the higher activity of aminocarboxymuconate-semialdehyde decarboxylase. As is known that this enzyme activity is induced by adrenal cortical hormone, it was suggested that the release of this hormone is stimulated by feeding the casein hydrolysate diet. PMID- 27280669 TI - Sterol Composition in the Pollens of Citrus unshiu Marcov. and Citrus sinensis Osbeck. PMID- 27280670 TI - Preservability and Utilization of Powdered alpha-Linolenic Acid with Egg White. PMID- 27280671 TI - Purification and Characterization of beta-Galactosidase from Enterobactev cloacae GAO. PMID- 27280672 TI - Effect of Cholesterol-loading on Plasma and Tissue Taurine Levels in Rats. PMID- 27280673 TI - Production and Use of Monoclonal Antibodies against Rice Embryo Lipoxygenase-3. PMID- 27280674 TI - Purification and Some Properties of Chitinase B1 from Bacillus circulans WL-12. PMID- 27280675 TI - Facile and Large-Scale Synthesis of L-Theanine. PMID- 27280676 TI - Accumulation of Isoflavones in Lupin Seedings Treated with Copper Chloride. PMID- 27280677 TI - Mendelian Inheritance of Paralytic Shellfish Poisoning Toxin in the Marine Dinoflagellate Alexandrium catenella. AB - To analyze the genetic system of paralytic shellfish poisoning (PSP) toxin production in the dinoflagellate Alexandrium catenella, we examined toxin compositions and mating type of Fl progenies from crosses between algal strains having different toxin compositions. In all strains used, the mole percentage of their toxin composition did not significantly change in any growth phase, although total toxin levels increased rapidly in the early to middle exponential growth phase and then decreased by 95% in the stationary phase. One parental strain produced gonyautoxin (GTX) 4, and C4, while the other produced neosaxitoxin (neoSTX) and saxitoxin (STX) during all growth phases. Fl progenies showed one parental toxin composition and segregated independently with the mating type. These data suggest that A. catenella is a toxin producer and that Mendelian inheritance of toxin profiles occurs in the heterothallic dinoflagellate A. catenella. PMID- 27280678 TI - Distinct Profiles of ADP- and UDP-Specific Sucrose Synthases in Developing Rice Grains. PMID- 27280680 TI - [What do General Practitioners and Dentists Report about their Cooperation? A Qualitative Exploration]. AB - OBJECTIVE: Against the background of well-described associations between oral and general health, the cooperation between general practitioners (GPs) and dentists is crucial. Besides treatment, this includes prevention. Administrative referral between these two professions is not provided by statute. Thus, the study addresses the question: How do dentists and GPs integrate the associations between oral and systemic health in daily routine? METHODS: A total of 28 semi structured interviews were conducted with GPs and dentists from 3 structurally different regions in the Federal State of Baden-Wurttemberg. Participants were visited in their office. The interviews were recorded, transcribed and analysed by 2 dentists and sociologists using Mayrings' qualitative content analysis. RESULTS: Associations between general and oral health are partially known to both practitioners. However, contact between them is limited. GPs send patients directly to dentists, without contacting them - mainly due to a desolate dental status, rarely due to therapy-resistant headache or facial pain. Dentists contact GPs to clarify mainly medication or anticoagulation medications taken by patients prior to invasive procedures. Preventive aspects play a minor part. Consultation essentially depends on acquaintanceship. CONCLUSION: Separation by statute determines the cooperation. Oral cavity in daily care is demarcated. Holistic patient care is hindered by a lack of knowledge and daily routines. PMID- 27280679 TI - Low Density Lipoprotein-Receptor Related Protein 1 Is Differentially Expressed by Neuronal and Glial Populations in the Developing and Mature Mouse Central Nervous System. AB - The low density lipoprotein-receptor related protein 1 (LRP1) is a large endocytic cell surface receptor that is known to interact with a variety of ligands, intracellular adaptor proteins and other cell surface receptors to regulate cellular behaviours ranging from proliferation to cell fate specification, migration, axon guidance, and lipid metabolism. A number of studies have demonstrated that LRP1 is expressed in the brain, yet it is unclear which central nervous system cell types express LRP1 during development and in adulthood. Herein we undertake a detailed study of LRP1 expression within the mouse brain and spinal cord, examining a number of developmental stages ranging from embryonic day 13.5 to postnatal day 60. We report that LRP1 expression in the brain peaks during postnatal development. On a cellular level, LRP1 is expressed by radial glia, neuroblasts, microglia, oligodendrocyte progenitor cells (OPCs), astrocytes and neurons, with the exception of parvalbumin+ interneurons in the cortex. Most cell populations exhibit stable expression of LRP1 throughout development; however, the proportion of OPCs that express LRP1 increases significantly from ~69% at E15.5 to ~99% in adulthood. We also report that LRP1 expression is rapidly lost as OPCs differentiate, and is absent from all oligodendrocytes, including newborn oligodendrocytes. While LRP1 function has been primarily examined in mature neurons, these expression data suggest it plays a more critical role in glial cell regulation-where expression levels are much higher. PMID- 27280681 TI - [Influence of Teamwork on Wellbeing And Emotional Exhaustion of Staff in German Rehabilitation Clinics]. AB - AIM: In the context of high prevalence rates of mental and psychosomatic disorders in the medical staff, emotional exhaustion and wellbeing are often considered as important indicators. Teamwork can have a positive influence on wellbeing of staff members. In the sector of rehabilitation, however, this is not sufficiently investigated. The aim of this study was to investigate aspects of teamwork as predictors of wellbeing and emotional exhaustion in staff at rehabilitation clinics in Germany. METHODS: Data was collected in 10 rehabilitation clinics, 9 of them could be included in the data analysis (n=306, 70% female, 68% age 40-59). Data was analyzed with multiple linear regression analyses. RESULTS: Staff reported moderate rates of emotional exhaustion and good rates of overall wellbeing. Results of the regression analysis show that cohesion (beta=0.27, p<0,001), team organization (beta=0.19, p<0,01) and age (beta=0.13, p<0,05) could predict wellbeing (F[3, 244]=19.38, p<0,05). Emotional exhaustion was predicted by cohesion (beta=- 0.37, p<0,001, F[1, 244]=39.19). CONCLUSION: Consequences of interpersonal andstructural aspects of teamwork are discussed as well as the potential relevance of interventions to improve teamwork, in order to enhance wellbeing and counteract emotional exhaustion of staff members. PMID- 27280682 TI - Arsenic Metabolism and Toxicity Influenced by Ferric Iron in Simulated Gastrointestinal Tract and the Roles of Gut Microbiota. AB - Iron (Fe) is a common trace element in drinking water. However, little is known about how environmental concentrations of Fe affect the metabolism and toxicity of arsenic (As) in drinking water. In this study, influence of Fe at drinking water-related concentrations (0.1, 0.3, and 3 mg Fe (total)/L) on As metabolism and toxicity, and the roles of gut microbiota during this process were investigated by using in vitro Simulator of the Human Intestinal Microbial Ecosystem (SHIME). Results showed that Fe had ability to decrease bioaccessible As by coflocculation in small intestine. 0.1 and 0.3 mg/L Fe significantly increased As methylation in simulated transverse and descending colon. Gut microbiota played an important role in alteration of As species, and Fe could affect As metabolism by changing the gut microbiota. Bacteroides, Clostridium, Alistipes, and Bilophila had As resistance and potential ability to methylate As. Cytotoxicity assays of effluents from simulated colons showed that the low levels of Fe decreased As toxicity on human hepatoma cell line HepG2, which might be due to the increase of methylated As. When assessing the health risk of As in drinking water, the residual Fe should be considered. PMID- 27280683 TI - In Vivo Site-Specific Protein Tagging with Diverse Amines Using an Engineered Sortase Variant. AB - Chemoenzymatic modification of proteins is an attractive option to create highly specific conjugates for therapeutics, diagnostics, or materials under gentle biological conditions. However, these methods often suffer from expensive specialized substrates, bulky fusion tags, low yields, and extra purification steps to achieve the desired conjugate. Staphylococcus aureus sortase A and its engineered variants are used to attach oligoglycine derivatives to the C-terminus of proteins expressed with a minimal LPXTG tag. This strategy has been used extensively for bioconjugation in vitro and for protein-protein conjugation in living cells. Here we show that an enzyme variant recently engineered for higher activity on oligoglycine has promiscuous activity that allows proteins to be tagged using a diverse array of small, commercially available amines, including several bioorthogonal functional groups. This technique can also be carried out in living Escherichia coli, enabling simple, inexpensive production of chemically functionalized proteins with no additional purification steps. PMID- 27280684 TI - Distilling complexity to advance cardiac tissue engineering. AB - The promise of cardiac tissue engineering is in the ability to recapitulate in vitro the functional aspects of a healthy heart and disease pathology as well as to design replacement muscle for clinical therapy. Parts of this promise have been realized; others have not. In a meeting of scientists in this field, five central challenges or "big questions" were articulated that, if addressed, could substantially advance the current state of the art in modeling heart disease and realizing heart repair. PMID- 27280685 TI - alpha-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease. AB - alpha-Synuclein accumulation and mitochondrial dysfunction have both been strongly implicated in the pathogenesis of Parkinson's disease (PD), and the two appear to be related. Mitochondrial dysfunction leads to accumulation and oligomerization of alpha-synuclein, and increased levels of alpha-synuclein cause mitochondrial impairment, but the basis for this bidirectional interaction remains obscure. We now report that certain posttranslationally modified species of alpha-synuclein bind with high affinity to the TOM20 (translocase of the outer membrane 20) presequence receptor of the mitochondrial protein import machinery. This binding prevented the interaction of TOM20 with its co-receptor, TOM22, and impaired mitochondrial protein import. Consequently, there were deficient mitochondrial respiration, enhanced production of reactive oxygen species, and loss of mitochondrial membrane potential. Examination of postmortem brain tissue from PD patients revealed an aberrant alpha-synuclein-TOM20 interaction in nigrostriatal dopaminergic neurons that was associated with loss of imported mitochondrial proteins, thereby confirming this pathogenic process in the human disease. Modest knockdown of endogenous alpha-synuclein was sufficient to maintain mitochondrial protein import in an in vivo model of PD. Furthermore, in in vitro systems, overexpression of TOM20 or a mitochondrial targeting signal peptide had beneficial effects and preserved mitochondrial protein import. This study characterizes a pathogenic mechanism in PD, identifies toxic species of wild-type alpha-synuclein, and reveals potential new therapeutic strategies for neuroprotection. PMID- 27280686 TI - A universal system to select gene-modified hepatocytes in vivo. AB - Many genetic and acquired liver disorders are amenable to gene and/or cell therapy. However, the efficiencies of cell engraftment and stable genetic modification are low and often subtherapeutic. In particular, targeted gene modifications from homologous recombination are rare events. These obstacles could be overcome if hepatocytes that have undergone genetic modification were to be selectively amplified or expanded. We describe a universally applicable system for in vivo selection and expansion of gene-modified hepatocytes in any genetic background. In this system, the therapeutic transgene is coexpressed with a short hairpin RNA (shRNA) that confers modified hepatocytes with resistance to drug induced toxicity. An shRNA against the tyrosine catabolic enzyme 4-OH phenylpyruvate dioxygenase protected hepatocytes from 4-[(2-carboxyethyl) hydroxyphosphinyl]-3-oxobutyrate, a small-molecule inhibitor of fumarylacetoacetate hydrolase. To select for specific gene targeting events, the protective shRNA was embedded in a microRNA and inserted into a recombinant adeno associated viral vector designed to integrate site-specifically into the highly active albumin locus. After selection of the gene-targeted cells, transgene expression increased 10- to 1000-fold, reaching supraphysiological levels of human factor 9 protein (50,000 ng/ml) in mice. This drug resistance system can be used to achieve therapeutically relevant transgene levels in hepatocytes in any setting. PMID- 27280688 TI - Curcumin: A new candidate for melanoma therapy? AB - Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin. PMID- 27280687 TI - RNAi targeting multiple cell adhesion molecules reduces immune cell recruitment and vascular inflammation after myocardial infarction. AB - Myocardial infarction (MI) leads to a systemic surge of vascular inflammation in mice and humans, resulting in secondary ischemic complications and high mortality. We show that, in ApoE(-/-) mice with coronary ligation, increased sympathetic tone up-regulates not only hematopoietic leukocyte production but also plaque endothelial expression of adhesion molecules. To counteract the resulting arterial leukocyte recruitment, we developed nanoparticle-based RNA interference (RNAi) that effectively silences five key adhesion molecules. Simultaneously encapsulating small interfering RNA (siRNA)-targeting intercellular cell adhesion molecules 1 and 2 (Icam1 and Icam2), vascular cell adhesion molecule 1 (Vcam1), and E- and P-selectins (Sele and Selp) into polymeric endothelial-avid nanoparticles reduced post-MI neutrophil and monocyte recruitment into atherosclerotic lesions and decreased matrix-degrading plaque protease activity. Five-gene combination RNAi also curtailed leukocyte recruitment to ischemic myocardium. Therefore, targeted multigene silencing may prevent complications after acute MI. PMID- 27280689 TI - Multifunctional Surface Manipulation Using Orthogonal Click Chemistry. AB - Polymer brushes are excellent substrates for the covalent immobilization of a wide variety of molecules due to their unique physicochemical properties and high functional group density. By using reactive microcapillary printing, poly(pentafluorophenyl acrylate) brushes with rapid kinetic rates toward aminolysis can be partially patterned with other click functionalities such as strained cyclooctyne derivatives and sulfonyl fluorides. This trireactive surface can then react locally and selectively in a one pot reaction via three orthogonal chemistries at room temperature: activated ester aminolysis, strain promoted azide-alkyne cycloaddition, and sulfur(VI) fluoride exchange, all of which are tolerant of ambient moisture and oxygen. Furthermore, we demonstrate that these reactions can also be used to create areas of morphologically distinct surface features on the nanoscale, by inducing buckling instabilities in the films and the grafting of nanoparticles. This approach is modular, and allows for the development of highly complex surface motifs patterned with different chemistry and morphology. PMID- 27280690 TI - Systematic Genetic Screen for Transcriptional Regulators of the Candida albicans White-Opaque Switch. AB - The human fungal pathogen Candida albicans can reversibly switch between two cell types named "white" and "opaque," each of which is stable through many cell divisions. These two cell types differ in their ability to mate, their metabolic preferences and their interactions with the mammalian innate immune system. A highly interconnected network of eight transcriptional regulators has been shown to control switching between these two cell types. To identify additional regulators of the switch, we systematically and quantitatively measured white opaque switching rates of 196 strains, each deleted for a specific transcriptional regulator. We identified 19 new regulators with at least a 10 fold effect on switching rates and an additional 14 new regulators with more subtle effects. To investigate how these regulators affect switching rates, we examined several criteria, including the binding of the eight known regulators of switching to the control region of each new regulatory gene, differential expression of the newly found genes between cell types, and the growth rate of each mutant strain. This study highlights the complexity of the transcriptional network that regulates the white-opaque switch and the extent to which switching is linked to a variety of metabolic processes, including respiration and carbon utilization. In addition to revealing specific insights, the information reported here provides a foundation to understand the highly complex coupling of white opaque switching to cellular physiology. PMID- 27280691 TI - The Chromatin Remodeling Component Arid1a Is a Suppressor of Spontaneous Mammary Tumors in Mice. AB - Human cancer genome studies have identified the SWI/SNF chromatin remodeling complex member ARID1A as one of the most frequently altered genes in several tumor types. Its role as an ovarian tumor suppressor has been supported in compound knockout mice. Here, we provide genetic and functional evidence that Arid1a is a bona fide mammary tumor suppressor, using the Chromosome aberrations occurring spontaneously 3 (Chaos3) mouse model of sporadic breast cancer. About 70% of mammary tumors that formed in these mice contained a spontaneous deletion removing all or part of one Arid1a allele. Restoration of Arid1a expression in a Chaos3 mammary tumor line with low Arid1a levels greatly impaired its ability to form tumors following injection into cleared mammary glands, indicating that ARID1A insufficiency is crucial for maintenance of these Trp53-proficient tumors. Transcriptome analysis of tumor cells before and after reintroduction of Arid1a expression revealed alterations in growth signaling and cell-cycle checkpoint pathways, in particular the activation of the TRP53 pathway. Consistent with the latter, Arid1a reexpression in tumor cells led to increased p21 (Cdkn1a) expression and dramatic accumulation of cells in G2 phase of the cell cycle. These results not only provide in vivo evidence for a tumor suppressive and/or maintenance role in breast cancer, but also indicate a potential opportunity for therapeutic intervention in ARID1A-deficient human breast cancer subtypes that retain one intact copy of the gene and also maintain wild-type TRP53 activity. PMID- 27280693 TI - Synthesis and Investigation of Tetrahydro-beta-carboline Derivatives as Inhibitors of the Breast Cancer Resistance Protein (ABCG2). AB - The breast cancer resistance protein (ABCG2) transports chemotherapeutic drugs out of cells, which makes it a major player in mediating multidrug resistance (MDR) of cancer cells. To overcome this mechanism, inhibitors of ABCG2 can be used. Only a few potent and selective ABCG2 inhibitors have been discovered, i.e., fumitremorgin C (FTC), Ko143, and the alkaloid harmine, which contain a tetrahydro-beta-carboline or beta-carboline backbone, respectively. However, toxicity and or instability prevent their use in vivo. Therefore, there is a need for further potent inhibitors. We synthesized and pharmacologically investigated 37 tetrahydro-beta-carboline derivatives. The inhibitory activity of two compounds (51, 52) is comparable to that of Ko143, and they are selective for ABCG2 over ABCB1. Furthermore, they are able to reverse the ABCG2-mediated resistance toward SN-38 and inhibit the ATPase activity. The cytotoxicity data show that their inhibitory effect is substantially higher than their toxicity. PMID- 27280692 TI - Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes in Caenorhabditis Species. AB - During meiosis in the heterogametic sex in some species, sex chromosomes undergo meiotic sex chromosome inactivation (MSCI), which results in acquisition of repressive chromatin and transcriptional silencing. In Caenorhabditis elegans, MSCI is mediated by MET-2 methyltransferase deposition of histone H3 lysine 9 dimethylation. Here we examined the meiotic chromatin landscape in germ lines of four Caenorhabditis species; C. remanei and C. brenneri represent ancestral gonochorism, while C. briggsae and C. elegans are two lineages that independently evolved hermaphroditism. While MSCI is conserved across all four species, repressive chromatin modifications are distinct and do not correlate with reproductive mode. In contrast to C. elegans and C. remanei germ cells where X chromosomes are enriched for histone H3 lysine 9 dimethylation, X chromosomes in C. briggsae and C. brenneri germ cells are enriched for histone H3 lysine 9 trimethylation. Inactivation of C. briggsae MET-2 resulted in germ-line X chromosome transcription and checkpoint activation. Further, both histone H3 lysine 9 di- and trimethylation were reduced in Cbr-met-2 mutant germ lines, suggesting that in contrast to C. elegans, H3 lysine 9 di- and trimethylation are interdependent. C. briggsae H3 lysine 9 trimethylation was redistributed in the presence of asynapsed chromosomes in a sex-specific manner in the related process of meiotic silencing of unsynapsed chromatin. However, these repressive marks did not influence X chromosome replication timing. Examination of additional Caenorhabditis species revealed diverse H3 lysine 9 methylation patterns on the X, suggesting that the sex chromosome epigenome evolves rapidly. PMID- 27280695 TI - All-Solution-Processed Organic Light-Emitting Diodes Based on Photostable Photo cross-linkable Fluorescent Small Molecules. AB - We demonstrate herein the fabrication of small molecule-based OLEDs where four organic layers from the hole- to the electron-transporting layers have successively been deposited by using an all-solution process. The key feature of the device relies on a novel photopolymerizable red-emitting material, made of small fluorophores substituted with two acrylate units, and displaying high quality film-forming properties as well as high emission quantum yield as nondoped thin films. Insoluble emissive layers were obtained upon UV irradiation using low illumination doses, with no further need of postcuring. Very low photodegradation was noticed, giving rise to bright layers with a remarkable surface quality, characterized by a mean RMS roughness as low as 0.7 nm after development. Comparative experiments between solution-processed OLEDs and vacuum processed OLEDs made of fluorophores with close architectures show external quantum efficiencies in the same range while displaying distinct behaviors in terms of current and power efficiencies. They validate the proof of concept of nondoped solution-processable emissive layers exclusively made of photopolymerized fluorophores, thereby reducing the amount of components and opening the way toward cost-effective fabrication of solution-processed OLED multilayer architectures. PMID- 27280694 TI - ImmunoPET Imaging of CD146 Expression in Malignant Brain Tumors. AB - Recently, the overexpression of CD146 and its potential as a therapeutic target in high-grade gliomas, the most lethal type of brain cancer, was uncovered. In this study, we describe the generation of (89)Zr-Df-YY146, a novel (89)Zr-labeled monoclonal antibody (mAb) for the targeting and quantification of CD146 expression in a mouse model of glioblastoma, using noninvasive immunoPET imaging. YY146, a high affinity anti-CD146 mAb, was conjugated to deferoxamine (Df) for labeling with the long-lived positron emitter (89)Zr (t1/2: 78.4 h). In vitro assays, including flow cytometry, immunofluorescence microscopy, and Western blot, were performed with two glioblastoma cell lines, U87MG and U251, to determine their CD146 expression levels. Also, YY146 and Df-YY146's CD146-binding affinities were compared using flow cytometry. In vivo CD146-targeting of (89)Zr Df-YY146 was evaluated by sequential PET imaging, in athymic nude mice bearing subcutaneously implanted U87MG or U251 tumors. CD146 blocking, ex vivo biodistribution, and histological studies were carried out to confirm (89)Zr-Df YY146 specificity, as well as the accuracy of PET data. In vitro studies exposed elevated CD146 expression levels in U87MG cells, but negligible levels in U251 cells. Flow cytometry revealed no differences in affinity between YY146 and Df YY146. (89)Zr labeling of Df-YY146 proceeded with excellent yield (~80%), radiochemical purity (>95%), and specific activity (~44 GBq/MUmol). Longitudinal PET revealed prominent and persistent (89)Zr-Df-YY146 uptake in mice bearing U87MG tumors that peaked at 14.00 +/- 3.28%ID/g (n = 4), 48 h post injection of the tracer. Conversely, uptake was significantly lower in CD146-negative U251 tumors (5.15 +/- 0.99%ID/g, at 48 h p.i.; n = 4; P < 0.05). Uptake in U87MG tumors was effectively blocked in a competitive inhibition experiment, corroborating the CD146 specificity of (89)Zr-Df-YY146. Finally, ex vivo biodistribution validated the accuracy of PET data and histological examination successfully correlated tracer uptake with in situ CD146 expression. Prominent, persistent, and specific uptake of (89)Zr-Df-YY146 was observed in brain tumors, demonstrating the potential of this radiotracer for noninvasive PET imaging of CD146 expression. In a future clinical scenario, (89)Zr-Df-YY146 may serve as a tool to guide intervention and assess response to CD146-targeted therapies. PMID- 27280696 TI - Applications of CRISPR-Cas in its natural habitat. AB - Key components of CRISPR-Cas systems have been adapted into a powerful genome editing tool that has caught the headlines and the attention of the public. Canonically, a customized RNA serves to guide an endonuclease (e.g. Cas9) to its DNA target, resulting in precise genomic lesions that can be repaired in a personalized fashion by cellular machinery. Here, we turn to the microbes that are the source of this system to explore many of its other notable applications. These include mining the CRISPR 'memory' arrays for functional genomic data, generation of customized virus-resistant or plasmid-refractory bacterial cells, editing of previously intractable viral genomes, and exploiting the unique properties of a catalytically inactive Cas9, dCas9, to serve as a highly customizable anti-nucleic acid 'antibody'. PMID- 27280697 TI - Deletion of the N- or C-Terminal Helix of Apolipophorin III To Create a Four Helix Bundle Protein. AB - Apolipophorin III (apoLp-III) is an exchangeable apolipoprotein found in insects and plays an important function in lipid transport. The protein has an unusual five-helix bundle architecture, deviating from the common four-helix bundle motif. To understand the role of the additional helix in apoLp-III, the N terminal or C-terminal helix was deleted to create a putative four-helix bundle protein. While the protein lacking helix-1 could be expressed in bacteria albeit at reduced yields, apoLp-III lacking helix-5 could not be produced. Mutational analysis by truncating helix-5 showed that a minimum segment of approximately one third of the C-terminal helix is required for protein expression. The variant lacking helix-5 was produced by inserting a methionine residue between helix-4 and -5; subsequent cyanogenbromide cleavage generated the four-helix variant. Both N- and C-terminal helix deletion variants displayed significantly reduced helical content, protein stability, and tertiary structure. Despite the significantly altered structure, the variants were still fully functional. The rate of dimyristoylphosphatidylcholine vesicle solubilization was enhanced 4-5 fold compared to the wild-type protein, and the deletion variants were effective in binding to lipolyzed low density lipoprotein thereby preventing lipoprotein aggregation. These results show that the additional helix of apoLp-III is not essential for lipid binding but is required for proper folding to keep the protein into a stable conformation. PMID- 27280698 TI - Alternating or Metronome Pisa Syndrome in Patients Under Drugs Acting on Dopaminergic Pathways. PMID- 27280699 TI - Paroxysmal Nonkinesigenic Dyskinesias Responsive to Carbamazepine in Fahr Syndrome: A Case Report. AB - OBJECTIVE: This study aimed to report the case of a patient with paroxysmal nonkinesigenic dyskinesias and Fahr syndrome who had a marked response to carbamazepine. METHODS: We present the case of a 57-year-old female patient with episodes of paroxysmal choreoathetoid dyskinesias in the oromandibular region and distal region of upper and lower extremities, with fluctuating dystonic postures in the same distribution; duration was variable ranging from 30 minutes to 3 hours. Laboratory studies were consistent with primary hyperparathyroidism with bilateral brain calcifications. RESULTS: Treatment with low doses of carbamazepine was successful. PMID- 27280701 TI - Rapid and sensitive detection of fipronil and its metabolites in edible oils by solid-phase extraction based on humic acid bonded silica combined with gas chromatography with electron capture detection. AB - Solid-phase extraction based on humic acid bonded silica followed by gas chromatography with electron capture detection was developed to determine fipronil and its metabolites in edible oil. To achieve the best extraction performance, we systematically investigated a series of solid-phase extraction parameters. Under the optimized conditions, the method was validated according to linearity, recovery, and precision. Good linearities were obtained with R(2) more than 0.9996 for all analytes. The limits of detection were between 0.3 and 0.5 ng/g, and the recoveries ranged from 83.1 to 104.0% at three spiked concentrations with intra- and interday relative standard deviation values less than 8.7%. Finally, the proposed method was applied to determine fipronil and its metabolites in 11 edible oil samples taken from Wuhan markets. Fipronil was detectable in four samples with concentrations ranging from 3.0 to 5.2 ng/g. In China, the maximum residue limits of fipronil in some vegetables and maize are 20 and 100 ng/g (GB/T 2763-2014), respectively. The residues of fipronil and its metabolites in commercial edible oils might exhibit some potential threat to human health as a result of high consumption of edible oil as part of daily intake. PMID- 27280700 TI - Molecular Portrait of Oral Tongue Squamous Cell Carcinoma Shown by Integrative Meta-Analysis of Expression Profiles with Validations. AB - Oral Tongue Squamous cell carcinoma (OTSCC), the most frequently affected oral cancer sub-site, is associated with a poor therapeutic outcome and survival despite aggressive multi- modality management. Till date, there are no established biomarkers to indicate prognosis and outcome in patients presenting with tongue cancer. There is an urgent need for reliable molecular prognostic factors to enable identification of patients with high risk of recurrence and treatment failure in OTSCC management. In the current study, we present the meta analysis of OTSCC microarray based gene expression profiles, deriving a comprehensive molecular portrait of tongue cancer biology, showing the relevant genes and pathways which can be pursued further to derive novel, tailored therapeutics as well as for prognostication. We have studied 5 gene expression profiling data sets available on exclusively oral tongue subsite comprising of sample size; n = 190, consisting of 111 tumors and 79 normals. The meta- analysis results showed 2405 genes differentially regulated comparing OTSCC tumor and normal. The top up regulated genes were found to be involved in Extracellular matrix degradation (ECM) and Epithelial to mesenchymal transition (EMT) pathways. The top down regulated genes were found to be involved in detoxication pathways. We validated the results in clinical samples (n = 206), comprising of histologically normals (n = 10), prospective (n = 29) and retrospective (n = 167) OTSCC by evaluating MMP9 and E-cadherin gene expression by qPCR and immunohistochemistry. Consistent with meta-analysis results, MMP9 mRNA expression was significantly up regulated in OTSCC primary tumors compared to normals. MMP9 protein over expression was found to be a significant predictor of poor prognosis, disease recurrence and poor Disease Free Survival (DFS) in OTSCC patients. Analysis by univariate and multivariate Cox proportional hazard model showed patients with loss of E-cadherin expression in OTSCC tumors having a poorer DFS (HR = 1.566; P value = 0.045) and poorer Overall Survival (OS) (HR = 1.224; P value = 0.003) respectively. Combined over-expression of MMP9 and loss of E-cadherin membrane positivity in the invasive tumor front (ITF) of OTSCC had a significant association with poorer DFS (Log Rank = 16.040; P value = 0.001). These results suggest that along with known clinical indicators of prognosis like occult node positivity, assessment of MMP9 and E-cadherin expression at ITF can be useful to identify patients at high risk and requiring a more intensive treatment strategy for OTSCC. Meta-analysis study of gene expression profiles indicates that OTSCC is a disease of ECM degradation leading to activated EMT processes implying the aggressive nature of the disease. The triggers for these processes should be studied further. Newer clinical application with agents that can inhibit the mediators of ECM degradation may be a key to achieving clinical control of invasion and metastasis of OTSCC. PMID- 27280702 TI - Role of Sub-Nanometer Dielectric Roughness on Microstructure and Charge Carrier Transport in alpha,omega-Dihexylsexithiophene Field-Effect Transistors. AB - The effect of dielectric roughness on the microstructure evolution of thermally evaporated alpha,omega-dihexylsexithiophene (alpha,omega-DH6T) thin films from a single molecular layer to tens of monolayers (ML) is studied. Thereby, the surface roughness of dielectrics is controlled within a sub-nanometer range. It is found that the grain size of an alpha,omega-DH6T ML is affected by dielectric roughness, especially for 1.5 ML, whereby the transistor performance is barely influenced. This can be attributed to a domain interconnection in the second layer over a long-range formed on the rough surface. With deposition of more layers, both microstructure and charge carrier transport exhibit a roughness independent behavior. The structural characterization of alpha,omega-DH6T 10 ML by grazing-incidence wide-angle X-ray scattering reveals that the interlayer distance is slightly decreased from 3.30 to 3.15 nm due to a higher roughness, while an unchanged pi-stacking distance is in excellent agreement with the roughness-independent hole mobility. This study excludes the influence of molecular-solvent interaction and preaggregation taking place during solution deposition, and provides further evidence that the microstructure of the interfacial layer of organic semiconductors has only minor impact on the bulk charge carrier transport in thicker films. PMID- 27280703 TI - Association of Fast Visual Field Loss With Risk of Falling in Patients With Glaucoma. AB - IMPORTANCE: Patients with glaucoma and a history of fast visual field loss might be at an increased risk for falls compared with those with a history of slow visual field loss, but, to date, this association has not been previously investigated in the literature. OBJECTIVE: To evaluate the association between self-reported falls and past rate of visual field loss in a cohort of patients with glaucoma followed up over time. DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study included patients diagnosed as having glaucoma who had been followed up at the Visual Performance Laboratory, University of California, San Diego, at 6-month intervals for a mean (SD) of 7.5 (2.6) years from January 1, 2005, through December 31, 2015. Self-reported number of falls during the past year was obtained at the last follow-up visit. Integrated binocular fields were estimated from the monocular fields. Linear mixed models were used to calculate rates of change in binocular mean sensitivity over time. Poisson models were used to evaluate the association between the self-reported number of falls and rates of visual field loss. The models adjusted for the current level of visual field damage and other confounding variables. MAIN OUTCOMES AND MEASURES: Association between rates of binocular visual field loss and self-reported number of falls. RESULTS: The study included 116 patients with glaucoma with a mean (SD) age of 73.1 (10.7) years (55 women [47.4%], 84 white individuals [72.4%], and 32 black individuals [27.6%]). Of the 116 patients, 29 (25.0%) reported at least 1 fall in the previous year. The mean rate of change in binocular mean sensitivity was faster for patients who reported a history of falls vs those who did not (-0.36 vs -0.17 dB/y; mean difference, 0.20 dB/y; 95% CI, 0.09-0.31 dB/y; P < .001). History of fast visual field loss was significantly associated with falls (rate ratio, 2.28 per 0.5 dB/y faster; 95% CI, 1.15-4.52 db/y; P = .02), even after adjusting for confounding factors. CONCLUSIONS AND RELEVANCE: The rate of visual field loss was associated with a self-reported history of falls in the past year even after taking into account the magnitude of visual field defect. However, although a positive association was found, further studies are necessary to establish whether a cause-and-effect relationship exists between rate of visual field loss and self-reported history of falls. PMID- 27280704 TI - Risk of Thromboembolic Events in Patients with Non-Valvular Atrial Fibrillation After Dabigatran or Rivaroxaban Discontinuation - Data from the Ljubljana Registry. AB - BACKGROUND AND AIM: Interruption of anticoagulant treatment with warfarin or non vitamin K antagonist oral anticoagulants (NOAC) represents a vulnerable period with an increased risk of thromboembolic events. What is the incidence of thromboembolic events in real-life patients with non-valvular atrial fibrillation treated with NOAC who had a discontinuation or cessation of treatment in comparison to patients on continuous treatment? PATIENTS AND METHODS: Registry data from 866 patients with non-valvular atrial fibrillation, aged 74.3 (SD 9.8) years, with an average CHADS2 score of 2.1 (SD 1.2), who were started on dabigatran or rivaroxaban, were analysed for thromboembolic events and survival. Patients who had temporary or permanent discontinuation of NOAC were compared to patients on continuous NOAC treatment. RESULTS: Among 866 patients started on NOAC, 705 were treated without interruption, 84 patients had temporary interruption (69 because of planned invasive procedures, 10 due to bleeding, 5 for other causes) and 77 had permanent cessation of NOAC treatment. In patients without interruptions, the incidence of thromboembolic events was 1.0 (95% CI 0.4 2.1) per 100 patient-years, while in patients with interruption/cessation the rate of thromboembolic events was 21.6 (95% CI 10.3-45.2) per 100 patient-years, p < 0.001. There was a distinct clustering of thromboembolic events in the first weeks of NOAC discontinuation with the median occurring on day 14 (range 1-37 days) after discontinuation. CONCLUSION: Dabigatran and rivaroxaban offered good protection against thromboembolic events during treatment, but interruption of NOAC treatment increased the short-term thromboembolic risk more than 20-fold. PMID- 27280705 TI - Correction: The Holstein Friesian Lethal Haplotype 5 (HH5) Results from a Complete Deletion of TBF1M and Cholesterol Deficiency (CDH) from an ERV-(LTR) Insertion into the Coding Region of APOB. AB - [This corrects the article DOI: 10.1371/journal.pone.0154602.]. PMID- 27280706 TI - Environmental Impacts of the U.S. Health Care System and Effects on Public Health. AB - The U.S. health care sector is highly interconnected with industrial activities that emit much of the nation's pollution to air, water, and soils. We estimate emissions directly and indirectly attributable to the health care sector, and potential harmful effects on public health. Negative environmental and public health outcomes were estimated through economic input-output life cycle assessment (EIOLCA) modeling using National Health Expenditures (NHE) for the decade 2003-2013 and compared to national totals. In 2013, the health care sector was also responsible for significant fractions of national air pollution emissions and impacts, including acid rain (12%), greenhouse gas emissions (10%), smog formation (10%) criteria air pollutants (9%), stratospheric ozone depletion (1%), and carcinogenic and non-carcinogenic air toxics (1-2%). The largest contributors to impacts are discussed from both the supply side (EIOLCA economic sectors) and demand side (NHE categories), as are trends over the study period. Health damages from these pollutants are estimated at 470,000 DALYs lost from pollution-related disease, or 405,000 DALYs when adjusted for recent shifts in power generation sector emissions. These indirect health burdens are commensurate with the 44,000-98,000 people who die in hospitals each year in the U.S. as a result of preventable medical errors, but are currently not attributed to our health system. Concerted efforts to improve environmental performance of health care could reduce expenditures directly through waste reduction and energy savings, and indirectly through reducing pollution burden on public health, and ought to be included in efforts to improve health care quality and safety. PMID- 27280707 TI - Leishmania amazonensis Engages CD36 to Drive Parasitophorous Vacuole Maturation. AB - Leishmania amastigotes manipulate the activity of macrophages to favor their own success. However, very little is known about the role of innate recognition and signaling triggered by amastigotes in this host-parasite interaction. In this work we developed a new infection model in adult Drosophila to take advantage of its superior genetic resources to identify novel host factors limiting Leishmania amazonensis infection. The model is based on the capacity of macrophage-like cells, plasmatocytes, to phagocytose and control the proliferation of parasites injected into adult flies. Using this model, we screened a collection of RNAi expressing flies for anti-Leishmania defense factors. Notably, we found three CD36-like scavenger receptors that were important for defending against Leishmania infection. Mechanistic studies in mouse macrophages showed that CD36 accumulates specifically at sites where the parasite contacts the parasitophorous vacuole membrane. Furthermore, CD36-deficient macrophages were defective in the formation of the large parasitophorous vacuole typical of L. amazonensis infection, a phenotype caused by inefficient fusion with late endosomes and/or lysosomes. These data identify an unprecedented role for CD36 in the biogenesis of the parasitophorous vacuole and further highlight the utility of Drosophila as a model system for dissecting innate immune responses to infection. PMID- 27280709 TI - Evidence for dual mechanisms of action prediction dependent on acquired visual motor experiences. AB - To test mechanisms underpinning action prediction, we directly controlled experience in a dart-throwing training study. A motor-visual group physically practiced throwing darts and a perceptual training group learned to associate dart throw actions (occluded video clips) with landing outcomes. A final control group did not practice. Accuracy was assessed on related prediction tests before and after practice (involving temporally occluded video clips). These tests were performed while additionally performing simple, action-incongruent secondary motor tasks with either the right (observed throwing arm) or left effector, in addition to an attention control task. Motor proficiency tests were also performed. Although both trained groups improved their prediction accuracy after training, only the motor-visual group showed interference associated with the right-arm secondary motor task after practice. No interference was shown for the left-arm motor task. These effects were evidenced regardless of whether predictions were made in response to video stimuli or static clips. Moreover, improvements on the motor proficiency test were only shown for the motor-visual group. These results show evidence in support of motor simulation processes during action prediction among observers with motor experience. Prediction accuracy can be achieved via nonmotor processes (for the perceptual group), but there was no evidence that physically experienced performers could effectively switch processes to maintain prediction accuracy. (PsycINFO Database Record PMID- 27280708 TI - IFI16 Preferentially Binds to DNA with Quadruplex Structure and Enhances DNA Quadruplex Formation. AB - Interferon-inducible protein 16 (IFI16) is a member of the HIN-200 protein family, containing two HIN domains and one PYRIN domain. IFI16 acts as a sensor of viral and bacterial DNA and is important for innate immune responses. IFI16 binds DNA and binding has been described to be DNA length-dependent, but a preference for supercoiled DNA has also been demonstrated. Here we report a specific preference of IFI16 for binding to quadruplex DNA compared to other DNA structures. IFI16 binds to quadruplex DNA with significantly higher affinity than to the same sequence in double stranded DNA. By circular dichroism (CD) spectroscopy we also demonstrated the ability of IFI16 to stabilize quadruplex structures with quadruplex-forming oligonucleotides derived from human telomere (HTEL) sequences and the MYC promotor. A novel H/D exchange mass spectrometry approach was developed to assess protein interactions with quadruplex DNA. Quadruplex DNA changed the IFI16 deuteration profile in parts of the PYRIN domain (aa 0-80) and in structurally identical parts of both HIN domains (aa 271-302 and aa 586-617) compared to single stranded or double stranded DNAs, supporting the preferential affinity of IFI16 for structured DNA. Our results reveal the importance of quadruplex DNA structure in IFI16 binding and improve our understanding of how IFI16 senses DNA. IFI16 selectivity for quadruplex structure provides a mechanistic framework for IFI16 in immunity and cellular processes including DNA damage responses and cell proliferation. PMID- 27280710 TI - Perceiving a continuous visual world across voluntary eye blinks. AB - People blink their eyes every few seconds, but the changes in retinal illumination that accompany eyeblinks are hardly noticed. Furthermore, despite the loss of visual input, visual experience remains continuous across eyeblinks. Two hypotheses were investigated to account for these phenomena. The first proposes that perceptual information is maintained across a blink whereas the second proposes that perceptual information is not maintained but rather postblink perceptual experience is antedated to the beginning of the blink. Two experiments found no evidence for temporal antedating of a stimulus presented during a voluntary eyeblink. In a third experiment subjects judged the temporal duration of a stimulus that was interrupted by a voluntary eyeblink with that of a stimulus presented while the eyes were open. The duration of stimuli that were interrupted by eyeblinks was judged to be 117 ms shorter than that of stimuli presented while the eyes remained open, indicating that blink duration was not accounted for in the perception of stimulus duration. This suggests that perceptual experience is neither maintained nor antedated across eyeblinks, but rather is ignored, perhaps in response to the extraretinal signal that accompanies the eyeblink. (PsycINFO Database Record PMID- 27280711 TI - Acting and anticipating: Impact of outcome-compatible distractor depends on response selection efficiency. AB - Action selection is thought to involve selection of the action's sensory outcomes. This notion is supported when encountering a distractor that resembles a learned response-outcome biases response selection. Some evidence, however, suggests that a larger contribution of stimulus-based response selection leaves little role for outcome-based selection, especially in forced-choice tasks with easily identifiable target stimuli. In the present study, we asked whether the contribution of outcome-based selection depends on the ease and efficiency of stimulus-based selection. If so, then efficient stimulus-based response selection should reduce the impact of an irrelevant distractor that resemble a response outcome. We manipulated efficiency of stimulus-based selection by varying the spatial relationship between stimulus and response (Experiment 1) and by varying stimulus discriminability (Experiments 2). We hypothesized that with efficient stimulus-based selection, outcome-based processes will play a weaker role in response selection, and performance will be less susceptible to outcome compatible or -incompatible distractors. By contrast, when stimulus-based selection is relatively inefficient, outcome-based processes will play a stronger role in response selection, and performance should be more susceptible to outcome compatible or -incompatible distractors. Confirming our predictions, our results showed stronger impact of the distractors when stimulus-based response selection was relatively inefficient. Finally, results of a control experiment (Experiment 3) suggested that learning the consistent response-outcome mapping is necessary for obtaining the effect of these distractors. We conclude that outcome-based processes do contribute to response selection in forced-choice tasks, and that this contribution varies with the efficiency of stimulus-based response selection. (PsycINFO Database Record PMID- 27280713 TI - Downregulation of the Deiminase PADI2 Is an Early Event in Colorectal Carcinogenesis and Indicates Poor Prognosis. AB - Peptidyl arginine deiminases (PADI) are a family of enzymes that catalyze the poorly understood posttranslational modification converting arginine residues into citrullines. In this study, the role of PADIs in the pathogenesis of colorectal cancer was investigated. Specifically, RNA expression was analyzed and its association with survival in a cohort of 98 colorectal cancer patient specimens with matched adjacent mucosa and 50 controls from donors without cancer. Key results were validated in an independent collection of tumors with matched adjacent mucosa and by mining of a publicly available expression data set. Protein expression was analyzed by immunoblotting for cell lines or IHC for patient specimens that further included 24 cases of adenocarcinoma with adjacent dysplasia and 11 cases of active ulcerative colitis. The data indicate that PADI2 is the dominantly expressed PADI enzyme in colon mucosa and is upregulated during differentiation. PADI2 expression is low or absent in colorectal cancer. Frequently, this occurs already at the stage of low-grade dysplasia. Mucosal PADI2 expression is also low in ulcerative colitis. The expression level of PADI2 in tumor and adjacent mucosa correlates with differential survival: low levels associate with poor prognosis. IMPLICATIONS: Downregulation of PADI2 is an early event in the pathogenesis of colorectal cancer associated with poor prognosis and points toward a possible role of citrullination in modulating tumor cells and their microenvironment. Mol Cancer Res; 14(9); 841-8. (c)2016 AACR. PMID- 27280712 TI - Anti-EBOV GP IgGs Lacking alpha1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs. AB - Polyclonal xenogenic IgGs, although having been used in the prevention and cure of severe infectious diseases, are highly immunogenic, which may restrict their usage in new applications such as Ebola hemorrhagic fever. IgG glycans display powerful xenogeneic antigens in humans, for example alpha1-3 Galactose and the glycolyl form of neuraminic acid Neu5Gc, and IgGs deprived of these key sugar epitopes may represent an advantage for passive immunotherapy. In this paper, we explored whether low immunogenicity IgGs had a protective effect on a guinea pig model of Ebola virus (EBOV) infection. For this purpose, a double knock-out pig lacking alpha1-3 Galactose and Neu5Gc was immunized against virus-like particles displaying surface EBOV glycoprotein GP. Following purification from serum, hyper immune polyclonal IgGs were obtained, exhibiting an anti-EBOV GP titer of 1:100,000 and a virus neutralizing titer of 1:100. Guinea pigs were injected intramuscularly with purified IgGs on day 0 and day 3 post-EBOV infection. Compared to control animals treated with IgGs from non-immunized double KO pigs, the anti-EBOV IgGs-treated animals exhibited a significantly prolonged survival and a decreased virus load in blood on day 3. The data obtained indicated that IgGs lacking alpha1-3 Galactose and Neu5Gc, two highly immunogenic epitopes in humans, have a protective effect upon EBOV infection. PMID- 27280715 TI - Correction: Honey Bee Inhibitory Signaling Is Tuned to Threat Severity and Can Act as a Colony Alarm Signal. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002423.]. PMID- 27280714 TI - Sleep and Mental Health in Undergraduate Students with Generally Healthy Sleep Habits. AB - Whereas previous research has indicated that sleep problems tend to co-occur with increased mental health issues in university students, relatively little is known about relations between sleep quality and mental health in university students with generally healthy sleep habits. Understanding relations between sleep and mental health in individuals with generally healthy sleep habits is important because (a) student sleep habits tend to worsen over time and (b) even time limited experience of sleep problems may have significant implications for the onset of mental health problems. In the present research, 69 university students with generally healthy sleep habits completed questionnaires about sleep quality and mental health. Although participants did not report clinically concerning mental health issues as a group, global sleep quality was associated with mental health. Regression analyses revealed that nighttime sleep duration and the frequency of nighttime sleep disruptions were differentially related to total problems and clinically-relevant symptoms of psychological distress. These results indicate that understanding relations between sleep and mental health in university students with generally healthy sleep habits is important not only due to the large number of undergraduates who experience sleep problems and mental health issues over time but also due to the potential to intervene and improve mental health outcomes before they become clinically concerning. PMID- 27280716 TI - Cleavage of the C(O)-S Bond of Thioesters by Palladium/Norbornene/Copper Cooperative Catalysis: An Efficient Synthesis of 2-(Arylthio)aryl Ketones. AB - A Pd/norbornene/Cu cooperative catalysis for the efficient synthesis of 2 (arylthio)aryl ketones from aryl halides and thioesters has been developed. The first example of cooperative catalysis by palladium, norbornene, and copper, wherein the C(O)-S bond of thioesters is cleaved by a Pd(II) palladacycle with the assistance of CuI, has been observed. PMID- 27280717 TI - The Effect of Maternal Death on the Health of the Husband and Children in a Rural Area of China: A Prospective Cohort Study. AB - OBJECTIVE: To examine the effects of maternal death on the health of the index child, the health and educational attainment of the older children, and the mental health and quality of life of the surviving husband. METHODS: A cohort study including 183 households that experienced a maternal death matched to 346 households that experienced childbirth but not a maternal death was conducted prospectively between June 2009 and October 2011 in rural China. Data on household sociodemographic characteristics, physical and mental health were collected using a quantitative questionnaire and medical examination at baseline and follow-up surveys. Multivariate linear regression, logistic regression models and difference-in-difference (DID) were used to compare differences of outcomes between two groups. FINDINGS: The index children who experienced the loss of a mother had a significantly higher likelihood of dying, abandonment and malnutrition compared to children whose mothers survived at the follow-up survey. The risk of not attending school on time and dropping out of school among older children in the affected group was higher than those in the control group during the follow-up. Husbands whose wife died had significantly lower EQ-5D index and EQ-VAS both at baseline and at follow-up surveys compared to those without experiencing a wife's death, suggesting an immediate and sustained poorer mental health quality of life among the surviving husbands. Also the prevalence of posttraumatic stress disorder (PTSD) was 72.6% at baseline and 56.2% at follow-up among husbands whose wife died. CONCLUSIONS: Maternal death has multifaceted and spillover effects on the physical and mental health of family members that are sustained over time. Programmes that reduce maternal mortality will mitigate repercussions on surviving family members are critical and needed. PMID- 27280718 TI - Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth. AB - Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer. PMID- 27280720 TI - Floor of Mouth Swelling. PMID- 27280721 TI - Effects of Mindfulness on Diabetes Mellitus: Rationale and Overview. AB - : Diabetes mellitus (DM) is an emerging global healthcare problem and its prevalence is increasing at an alarming rate. Despite improvements in both medical and pharmacological therapies, a complex medical condition may demand a diversified approach, such as: drug therapy, healthy diet and exercises, diabetes education programs, adherence to medical treatment and active participation of the patients in their lifestyle changes, such as stress management. The concept of mindfulness is here defined as the awareness that unfolds from the intention to attentively observe the current experience in a non-judgmental and non evaluative way. This state of awareness can be enhanced through the use of mindfulness-based interventions (MBIs), which have been associated to many physical and psychological health indicators. The aim of this overview is to offer the rationale and potential benefits of mindfulness in the control of DM and its complications. METHODS: a narrative review of the current and updated literature available on online database and which came up using the terms "mindfulness" and "diabetes mellitus". Mindfulness-based Interventions (MBIs) can be seen as preventive and complementary interventions in DM, particularly for the relief of symptoms related to depression and anxiety in diabetic patients and also in the management of other factors, including mindful eating, physical exercises and treatment adherence. Although many studies only present research protocols, mindfulness seems to have beneficial effects on all aspects of diabetes, including incidence, control and complications. Furthermore, longer term and more carefully controlled trials are necessary in order to draw consistent conclusions on the beneficial role of MBIs on DM. PMID- 27280722 TI - Color Vision Deficiency and Functional Disorders Among Israeli Male Adolescents Between 2007 and 2013. AB - Color vision deficiency has been associated with educational difficulties among male children, as well as attention-deficit hyperactivity disorder (ADHD). We examined the association of color vision deficiency with functional conditions, including ADHD, irritable bowel syndrome, enuresis and somatoform disorders, in a large population of male adolescents. We included all Israeli male adolescents that underwent medical and cognitive examinations during conscription between the years 2007 and 2013. The prevalence of ADHD, irritable bowel syndrome, enuresis, and somatoform disorders among color vision deficiency patients was compared to a control group. The study included 305 964 males aging 17 +/- 0.6, of which 7584 (2.5%) had color vision deficiency. Using a multivariable analysis, the probability for irritable bowel syndrome, enuresis, and somatoform disorders among color vision deficiency patients was increased by 1.41, 1.94, and 3.87, respectively (P < .05). No significant association was found between ADHD and color vision deficiency. Color vision abnormalities are associated with functional disorders in male adolescents, including irritable bowel syndrome, enuresis, and somatoform disorders. PMID- 27280719 TI - Connexin43 Forms Supramolecular Complexes through Non-Overlapping Binding Sites for Drebrin, Tubulin, and ZO-1. AB - Gap junctions are membrane specialization domains identified in most tissue types where cells abut each other. The connexin channels found in these membrane domains are conduits for direct cell-to-cell transfer of ions and molecules. Connexin43 (Cx43) is the most ubiquitous connexin, with critical roles in heart, skin, and brain. Several studies described the interaction between Cx43 and the cytoskeleton involving the actin binding proteins Zonula occludens (ZO-1) and drebrin, as well as with tubulin. However, a direct interaction has not been identified between drebrin and Cx43. In this study, co-IP and NMR experiments were used to demonstrate that the Cx43-CT directly interacts with the highly conserved N-terminus region of drebrin. Three Cx43-CT areas were found to be involved in drebrin binding, with residues 264-275 being critical for the interaction. Mimicking Src phosphorylation within this region (Y265) significantly disrupted the interaction between the Cx43-CT and drebrin. Immunofluorescence showed colocalization of Cx43, drebrin, and F-actin in astrocytes and Vero cells membrane, indicating that Cx43 forms a submembrane protein complex with cytoskeletal and scaffolding proteins. The co-IP data suggest that Cx43 indirectly interacts with F-actin through drebrin. Along with the known interaction of the Cx43-CT with ZO-1 and tubulin, the data presented here for drebrin indicate non-overlapping and separated binding sites for all three proteins for which simultaneous binding could be important in regulating cytoskeleton rearrangements, especially for neuronal migration during brain development. PMID- 27280723 TI - Epidemiology of Pediatric Convulsive Status Epilepticus With Fever in the Emergency Department: A Cohort Study of 381 Consecutive Cases. AB - Pediatric convulsive status epilepticus with fever is common in the emergency setting but leads to severe neurological sequelae in some patients. To explore the epidemiology of convulsive status epilepticus with fever, a retrospective cohort covering all convulsive status epilepticus cases with fever seen in the emergency department of a tertiary care children's hospital were consecutively collected. Of the 381 consecutive cases gathered, 81.6% were due to prolonged febrile seizure, 6.6% to encephalopathy/encephalitis, 0.8% to meningitis, and 7.6% to epilepsy. In addition, seizures were significantly longer in encephalopathy/encephalitis cases than in prolonged febrile seizure cases (log rank test, P < .001). These results provide for the first time the pretest probability of final diagnoses in children with convulsive status epilepticus with fever in the emergency setting, and will help optimize the management of pediatric patients presenting to the emergency department with convulsive status epilepticus with fever. PMID- 27280724 TI - Determinants of Grip Strength in Tunisian Nurses: A Bicentric Study. AB - BACKGROUND: Grip muscle force has always been used to assess functional limitations in elderly. Its use as a tool to assess work capacity has never been described in the literature. OBJECTIVE: To describe the patent determinants of grip strength and the usefulness of its measurement in assessing workability index in the healthcare sector. METHODS: This is a cross-sectional study conducted in a sample of 293 healthcare workers representative of 1181 based on a comprehensive questionnaire about socio-professional characteristics and on an 8 item work capacity evaluation (WAI). Besides, Body mass index was measured and muscle strength was assessed by JAMAR hydraulic dynamometer. RESULTS: Handgrip Strength was stronger in male nurses (p < 0.001), with low perceived physical load (p = 0.0001) and working on a night shift (p = 0.001). It decreased with a greater duration of household work (p < 0.0001) and increased with a greater BMI (p = 0.015) and a better workability index (p < 0.0001). After removal of all the variables that were not independently associated with the muscle strength force, factors accounting for 52.6% of the variance in nurses handgrip strength were gender (p < 0.001), workability index (p < 0.001), duration of household work (p = 0.021), BMI (p = 0.002), perceived physical load (p < 0.001) and work schedule (p = 0.002). CONCLUSION: Grip Strength Test is a useful tool to assess strength and functional capacity at work in healthcare workers. Further longitudinal studies are required to confirm this hypothesis. PMID- 27280725 TI - Correction: Influence of Obesity and Metabolic Disease on Carotid Atherosclerosis in Patients with Coronary Artery Disease (CordioPrev Study). AB - [This corrects the article DOI: 10.1371/journal.pone.0153096.]. PMID- 27280727 TI - Bayesian Evidence Synthesis Can Reconcile Seemingly Inconsistent Results: The Case of Hotel Towel Reuse. PMID- 27280726 TI - Coexpression Network Analysis of Benign and Malignant Phenotypes of SIV-Infected Sooty Mangabey and Rhesus Macaque. AB - To explore the differences between the extreme SIV infection phenotypes, nonprogression (BEN: benign) to AIDS in sooty mangabeys (SMs) and progression to AIDS (MAL: malignant) in rhesus macaques (RMs), we performed an integrated dual positive-negative connectivity (DPNC) analysis of gene coexpression networks (GCN) based on publicly available big data sets in the GEO database of NCBI. The microarray-based gene expression data sets were generated, respectively, from the peripheral blood of SMs and RMs at several time points of SIV infection. Significant differences of GCN changes in DPNC values were observed in SIV infected SMs and RMs. There are three groups of enriched genes or pathways (EGPs) that are associated with three SIV infection phenotypes (BEN+, MAL+ and mixed BEN+/MAL+). The MAL+ phenotype in SIV-infected RMs is specifically associated with eight EGPs, including the protein ubiquitin proteasome system, p53, granzyme A, gramzyme B, polo-like kinase, Glucocorticoid receptor, oxidative phosyphorylation and mitochondrial signaling. Mitochondrial (endosymbiotic) dysfunction is solely present in RMs. Specific BEN+ pattern changes in four EGPs are identified in SIV-infected SMs, including the pathways contributing to interferon signaling, BRCA1/DNA damage response, PKR/INF induction and LGALS8. There are three enriched pathways (PRR-activated IRF signaling, RIG1-like receptor and PRR pathway) contributing to the mixed (BEN+/MAL+) phenotypes of SIV infections in RMs and SMs, suggesting that these pathways play a dual role in the host defense against viral infections. Further analysis of Hub genes in these GCNs revealed that the genes LGALS8 and IL-17RA, which positively regulate the barrier function of the gut mucosa and the immune homeostasis with the gut microbiota (exosymbiosis), were significantly differentially expressed in RMs and SMs. Our data suggest that there exists an exo- (dysbiosis of the gut microbiota) and endo- (mitochondrial dysfunction) symbiotic imbalance (EESI) in HIV/SIV infections. Dissecting the mechanisms of the exo-endo symbiotic balance (EESB) that maintains immune homeostasis and the EESI problems in HIV/SIV infections may lead to a better understanding of the pathogenesis of AIDS and the development of novel interventions for the rational control of this disease. PMID- 27280728 TI - A Small Molecule Inhibitor Selectively Induces Apoptosis in Cells Transformed by High Risk Human Papilloma Viruses. AB - A phenotypic high-throughput cell culture screen was performed to identify compounds that prevented proliferation of the human Papilloma virus type 16 (HPV 16) transformed cell line Ca Ski. A series of quinoxaline compounds exemplified by Compound 1 was identified. Testing against a panel of cell lines demonstrated that Compound 1 selectively inhibited replication of all HPV-16, HPV-18, and HPV 31 transformed cell lines tested with 50% Inhibitory Concentration (IC50) values of 2 to 8 MUM relative to IC50 values of 28 to 73 MUM in HPV-negative cell lines. Treatment with Compound 1 resulted in a cascade of multiple apoptotic events, including selective activation of effector caspases 3 and 7, fragmentation of cellular DNA, and PARP (poly(ADP-ribose) polymerase) cleavage in HPV-positive cells relative to HPV-negative cells. Unregulated proliferation of HPV transformed cells is dependent on the viral oncogenes, E6 and E7. Treatment with Compound 1 resulted in a decrease in HPV E7 protein in Ca Ski cells. However, the timing of this reduction relative to other effects of compound treatment suggests that this was a consequence, rather than a cause, of the apoptotic cascade. Likewise, compound treatment resulted in no obvious effects on the E6- and E7- mediated down regulation of p53 and Rb, or their downstream effectors, p21 or PCNA. Further investigation of apoptotic signals induced by Compound 1 revealed cleavage of Caspase-8 in HPV-positive cells as early as 2 hours post-treatment, suggesting the compound initiates apoptosis through the extrinsic, death receptor mediated, pathway of cell death. These studies provide proof of concept that cells transformed by oncogenic Papillomaviruses can be selectively induced to undergo apoptosis by compound treatment. PMID- 27280730 TI - Vibrationally high-resolved electronic spectra of MCl2 (M=C, Si, Ge, Sn, Pb) and photoelectron spectra of MCl2(.). AB - We systematically studied the vibrational-resolved electronic spectra of group IV dichlorides using the Franck-Condon approximation combined with the Duschinsky and Herzberg-Teller effects in harmonic and anharmonic frameworks (only the simulation of absorption spectra includes the anharmonicity). Calculated results showed that the band shapes of simulated spectra are in accordance with those of the corresponding experimental or theoretical ones. We found that the symmetric bend mode in progression of absorption is the most active one, whereas the main contributor in photoelectron spectra is the symmetric stretching mode. Moreover, the Duschinsky and anharmonic effects exert weak influence on the absorption spectra, except for PbCl2 molecule. The theoretical insights presented in this work are significant in understanding the photophysical properties of MCl2 (M=C, Si, Ge, Sn, Pb) and studying the Herzberg-Teller and the anharmonic effects on the absorption spectra of new dichlorides of this main group. PMID- 27280729 TI - Stabilising the Integrity of Snake Venom mRNA Stored under Tropical Field Conditions Expands Research Horizons. AB - BACKGROUND: Snake venoms contain many proteinaceous toxins that can cause severe pathology and mortality in snakebite victims. Interestingly, mRNA encoding such toxins can be recovered directly from venom, although yields are low and quality is unknown. It also remains unclear whether such RNA contains information about toxin isoforms and whether it is representative of mRNA recovered from conventional sources, such as the venom gland. Answering these questions will address the feasibility of using venom-derived RNA for future research relevant to biomedical and antivenom applications. METHODOLOGY/PRINCIPAL FINDINGS: Venom was extracted from several species of snake, including both members of the Viperidae and Elapidae, and either lyophilized or immediately added to TRIzol reagent. TRIzol-treated venom was incubated at a range of temperatures (4-37 degrees C) for a range of durations (0-48 hours), followed by subsequent RNA isolation and assessments of RNA quantity and quality. Subsequently, full-length toxin transcripts were targeted for PCR amplification and Sanger sequencing. TRIzol-treated venom yielded total RNA of greater quantity and quality than lyophilized venom, and with quality comparable to venom gland-derived RNA. Full length sequences from multiple Viperidae and Elapidae toxin families were successfully PCR amplified from TRIzol-treated venom RNA. We demonstrated that venom can be stored in TRIzol for 48 hours at 4-19 degrees C, and 8 hours at 37 degrees C, at minimal cost to RNA quality, and found that venom RNA encoded multiple toxin isoforms that seemed homologous (98-99% identity) to those found in the venom gland. CONCLUSIONS/SIGNIFICANCE: The non-invasive experimental modifications we propose will facilitate the future investigation of venom composition by using venom as an alternative source to venom gland tissue for RNA based studies, thus obviating the undesirable need to sacrifice snakes for such research purposes. In addition, they expand research horizons to rare, endangered or protected snake species and provide more flexibility to performing fieldwork on venomous snakes in tropical conditions. PMID- 27280731 TI - Story Goodness in Adolescents With Autism Spectrum Disorder (ASD) and in Optimal Outcomes From ASD. AB - PURPOSE: This study examined narrative quality of adolescents with autism spectrum disorder (ASD) using a well-studied "story goodness" coding system. METHOD: Narrative samples were analyzed for distinct aspects of story goodness and rated by naive readers on dimensions of story goodness, accuracy, cohesiveness, and oddness. Adolescents with high-functioning ASD were compared with adolescents with typical development (TD; n = 15 per group). A second study compared narratives from adolescents across three groups: ASD, TD, and youths with "optimal outcomes," who were diagnosed with ASD early in development but no longer meet criteria for ASD and have typical behavioral functioning. RESULTS: In both studies, the ASD group's narratives had lower composite quality scores compared with peers with typical development. In Study 2, narratives from the optimal outcomes group were intermediate in scores and did not differ significantly from those of either other group. However, naive raters were able to detect qualitative narrative differences across groups. CONCLUSIONS: Findings indicate that pragmatic deficits in ASD are salient and could have clinical relevance. Furthermore, results indicate subtle differences in pragmatic language skills for individuals with optimal outcomes despite otherwise typical language skills in other domains. These results highlight the need for clinical interventions tailored to the specific deficits of these populations. PMID- 27280732 TI - Monitoring Vasculitis with 18F-FDG PET. AB - Whereas in the past the term "vasculitis" was most frequently used in context with systemic vasculitides, such as the large vessel vasculitides (LVV) Takayasa arteritis and giant cell arteritis, characterized by inflammation of blood vessel walls, it nowadays comprises also inflammatory changes of the vessel wall as a substantial part of the atherosclerotic disease process. Implementing non invasive imaging techniques, such as computed tomography angiography (CTA), magnetic resonance angiography (MRA) as well as positron emission tomography (PET) in the diagnostic algorithm of atherosclerosis and LVV, depicts a promising step towards an earlier detection with a, consecutively, improved therapeutic approach and potentially prognostic benefit in patients suffering from vasculitis. Mainly molecular imaging with 18F-fluorodeoxyglucose (FDG) PET seems to be promising in offering an early and sensitive identification of inflammatory changes in both, atherosclerosis and LVV. This review will therefore provide an overview on the diagnostic performance and clinical relevance of FDG-PET in monitoring vasculitis in atherosclerosis and LVV, with a focus on LVV. PMID- 27280733 TI - New molecular probes of vascular inflammation. AB - New molecular imaging approaches featuring the assessment of inflammatory processes in the vascular wall on top of existing anatomic and functional vessel imaging procedures could emerge as decisive tools for the understanding and prevention of cardiovascular events. In this respect imaging approaches addressing specific molecular and cellular targets in atherosclerosis are of high interest. This review summarizes the rationale and current status of nuclear imaging probes which possess high translational potential. PMID- 27280735 TI - Enabling the Discovery and Virtual Screening of Potent and Safe Antimicrobial Peptides. Simultaneous Prediction of Antibacterial Activity and Cytotoxicity. AB - Antimicrobial peptides (AMPs) represent promising alternatives to fight against bacterial pathogens. However, cellular toxicity remains one of the main concerns in the early development of peptide-based drugs. This work introduces the first multitasking (mtk) computational model focused on performing simultaneous predictions of antibacterial activities, and cytotoxicities of peptides. The model was created from a data set containing 3592 cases, and it displayed accuracy higher than 96% for classifying/predicting peptides in both training and prediction (test) sets. The technique known as alanine scanning was computationally applied to illustrate the calculation of the quantitative contributions of the amino acids (in their respective positions of the sequence) to the biological effects of a defined peptide. A small library formed by 10 peptides was generated, where peptides were designed by considering the interpretations of the different descriptors in the mtk-computational model. All the peptides were predicted to exhibit high antibacterial activities against multiple bacterial strains, and low cytotoxicity against various cell types. The present mtk-computational model can be considered a very useful tool to support high throughput research for the discovery of potent and safe AMPs. PMID- 27280736 TI - Stress Distribution in All-Ceramic Posterior 4-Unit Fixed Dental Prostheses Supported in Different Ways: Finite Element Analysis. AB - INTRODUCTION: The purpose of this finite element analysis (FEA) was to complement results of previously published studies that investigated the influence of abutment resilience on the load-bearing capacity of zirconia posterior 4-unit fixed dental prostheses (FDPs) with static load tests. MATERIALS AND METHODS: Duplicates of 3 different physical specimens were modeled for FEA. The first virtual specimen was supported by teeth with periodontal resilience, the second by the combination of tooth and implant, and the third by implants only. The center of the FDP was loaded, vertically to the occlusal plane. The highest maximum principal stresses (MPSs) were computed. DISCUSSION: The highest MPS in each model occurred in the basal region of the middle framework connector. Comparison between the 3 models showed that the tensile stresses were lower when the support of the FDP was more rigid. Numerically determined highest MPSs in the FDPs correlated well with experimentally observed load-bearing capacities. CONCLUSION: The FEA is well suited to confirm the in vitro study mentioned and complement the results with stress distributions in all-ceramic posterior 4-unit FDP. PMID- 27280734 TI - Effect of detergent binding on cytochrome P450 2B4 structure as analyzed by X-ray crystallography and deuterium-exchange mass spectrometry. AB - Multiple crystal structures of CYP2B4 have demonstrated the binding of the detergent 5-cyclohexyl-1-pentyl-beta-D-maltoside (CYMAL-5) in a peripheral pocket located adjacent to the active site. To explore the consequences of detergent binding, X-ray crystal structures of the peripheral pocket mutant CYP2B4 F202W were solved in the presence of hexaethylene glycol monooctyl ether (C8E6) and CYMAL-5. The structure in the presence of CYMAL-5 illustrated a closed conformation indistinguishable from the previously solved wild-type. In contrast, the F202W structure in the presence of C8E6 revealed a detergent molecule that coordinated the heme-iron and extended to the protein surface through the substrate access channel 2f. Despite the overall structural similarity of these detergent complexes, remarkable differences were observed in the A, A', and H helices, the F-G cassette, the C-D and beta4 loop region. Hydrogen-deuterium exchange mass spectrometry (DXMS) was employed to probe these differences and to test the effect of detergents in solution. The presence of either detergent increased the H/D exchange rate across the plastic regions, and the results obtained by DXMS in solution were consistent in general with the relevant structural snapshots. The study provides insight into effect of detergent binding and the interpretation of associated conformational dynamics of CYP2B4. PMID- 27280737 TI - A Non-Invasive and Accurate Measurement of Gingival Thickness Using Cone-Beam Computerized Imaging for the Assessment of Planning Immediate Implant in the Esthetic Zone-A Pig Jaw Model. AB - INTRODUCTION: The objective of the study is to compare the accuracy of the measurement of gingival thickness using cone-beam computerized tomography (CBCT) with direct clinical measurement on a pig jaw model, aiming to provide an alternate and precise method to aid assessment of the gingival biotype before immediate implant placement at the esthetic zone. MATERIALS AND METHODS: Four pig mandibles were categorized separately into 14 different zones with each prominent tooth cusp as one. A high-resolution CBCT image was taken. Measurement of gingival thickness was performed using computer software and was compared with direct clinical measurements. RESULTS: Intraclass correlation coefficient between clinical and CBCT measurements were 0.995 (pig 1), 0.945 (pig 2), 0.966 (pig 3), and 0.932 (pig 4), which indicated a good match between 2 measuring methods. Independent t test showed no significant difference between 2 independent investigators in all aspect of measurements (P > 0.05). CONCLUSION: Measuring gingival thickness using CBCT is a predictable and accurate method to assess the gingival biotype of a patient, so as to predict the suitability of immediate implantation. PMID- 27280740 TI - pi-Hydrogen Bonding of Aromatics on the Surface of Aerosols: Insights from Ab Initio and Molecular Dynamics Simulation. AB - Molecular level insight into the interaction between volatile organic compounds (VOCs) and aerosols is crucial for improvement of atmospheric chemistry models. In this paper, the interaction between adsorbed toluene, one of the most significant VOCs in the urban atmosphere, and the aqueous surface of aerosols was studied by means of combined molecular dynamics simulations and ab initio quantum chemistry calculations. It is revealed that toluene can be stably adsorbed on the surface of aqueous droplets via hydroxyl-pi hydrogen bonding between the H atoms of the water molecules and the C atoms in the aromatic ring. Further, significant modifications on the electrostatic potential map and frontier molecular orbital are induced by the solvation effect of surface water molecules, which would affect the reactivity and pathway of the atmospheric photooxidation of toluene. This study demonstrates that the surface interactions should be taken into consideration in the atmospheric chemical models on oxidation of aromatics. PMID- 27280738 TI - Fracture Resistance of Internal Conical and External Hexagon: Regular and Narrow Implant-Abutment Assemblies. AB - PURPOSE: The aim of this study was to compare the maximum load on the elastic limit of internal conical (IC) implants with regular external hexagon (REH) and narrow external hexagon (NEH) implants. MATERIALS AND METHODS: Thirty cylindrical implants were divided in 3 groups (n = 10): REH (3.75 mm); NEH (3.3 mm); IC (3.5 mm). The implants were evaluated by means of cantilever bending loads using a mechanical testing machine. A strain qualitative analysis and the corresponding angles were analyzed. Using single factor analysis of variance with Tukey Test and Friedman Test (P < 0.05) the statistical analysis for data were performed. RESULTS: REH (294.37 N) and IC (294.37 N) groups presented statistically greater Fle than NEH (189.16 N). Regarding to the strain, there were no significant differences among groups. However, there were a greater number of fissures and more fractures present on NEH group. CONCLUSION: The IC implant with smaller diameter did not result in reduction of elastic limit when compared with the REH implants. Nevertheless, the reduction of 0.45 mm of the hexagonal connection implant's diameter has significantly diminished the elastic limit. PMID- 27280741 TI - A cross-sectional study on clinical correlates of anxiety disorders in 613 community living older adults in Hong Kong. AB - OBJECTIVES: Previous studies have reported that the prevalence of late life anxiety disorders varies between 3.2% and 15.3%. Despite its high prevalence, anxiety disorders are still under-recognized in old age. This study evaluated the association among health, psychosocial factors, lifestyle choices, cognitive function and anxiety disorders in the older population in Hong Kong. METHODS: Six hundred and thirteen volunteer participants aged 60 years or above were interviewed for their socio-demographic background, physical and mental health statuses, social network, cognitive function and their activity engagement style. Ascertainment of diagnosis of anxiety disorders was based on the use of ICD-10 diagnostic criteria generated by the Revised Clinical Interview Schedule (CIS-R) algorithms. RESULTS: According to the ICD-10 diagnostic criteria generated by the CIS-R algorithms, 4.4% (N = 27) had mixed anxiety and depressive disorder, 2.5% (N = 15) had generalized anxiety disorders and 0.2% (N = 1) had other anxiety disorders (Phobia). Individuals with anxiety disorders had more gastrointestinal conditions (OR = 2.66, 95% CI 1.48-4.76) and genitourinary problems (OR = 1.96, 95% CI 1.05-3.65), poor 10-min delayed recall (OR = 0.68, 95% CI 0.56-0.83), worse abstract thinking (OR = 0.65, 95% CI 0.49-0.85) and poor social networking in confidante relationship (OR = 0.88, 95% CI 0.79-0.98). Lifestyle activity engagement was not associated with the presence of anxiety disorders. CONCLUSIONS: Older adults with anxiety disorders appeared to have greater medical comorbidity and lower cognitive function. While anxiety may affect memory performance, future studies are needed to explore if anxiety symptom may reflect early neurodegeneration that easily escapes clinical attention. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27280742 TI - Exploratory and hierarchical factor analysis of the WJ-IV Cognitive at school age. AB - Exploratory and confirmatory factor analytic studies were not reported in the Technical Manual for the Woodcock-Johnson, 4th ed. Cognitive (WJ IV Cognitive; Schrank, McGrew, & Mather, 2014b) Instead, the internal structure of the WJ IV Cognitive was extrapolated from analyses based on the full WJ IV test battery (Schrank, McGrew, & Mather, 2014b). Even if the veracity of extrapolating from the WJ IV full battery were accepted, there were shortcomings in the choices of analyses used and only limited information regarding those analyses was presented in the WJ IV Technical Manual (McGrew, Laforte, & Shrank, 2014). The present study examined the structure of the WJ IV Cognitive using exploratory factor analysis procedures (principal axis factoring with oblique [promax] rotation followed by application of the Schmid-Leiman, 1957, procedure) applied to standardization sample correlation matrices for 2 school age groups (ages 9-13; 14-19). Four factors emerged for both the 9-13 and 14-19 age groups in contrast to the publisher's proposed 7 factors. Results of these analyses indicated a robust manifestation of general intelligence (g) that exceeded the variance attributed to the lower-order factors. Model-based reliability estimates supported interpretation of the higher-order factor (i.e., g). Additional analyses were conducted by forcing extraction of the 7 theoretically posited factors; however, the resulting solution was only partially aligned (i.e., Gs, Gwm) with the theoretical structure promoted in the Technical Manual and suggested the preeminence of the higher-order factor. Results challenge the hypothesized structure of the WJ IV Cognitive and raise concerns about its alignment with Cattell-Horn-Carroll theory. (PsycINFO Database Record PMID- 27280743 TI - Using item response theory (IRT) to reduce patient burden when assessing desire for hastened death. AB - Desire for hastened death (DHD) represents a wish to die sooner than might occur by natural disease progression. Efficient and accurate assessment of DHD is vital for clinicians providing care to terminally ill patients. The Schedule of Attitudes Toward Hastened Death (SAHD) is a commonly used self-report measure of DHD. The goal of this study was to use methods grounded in item response theory (IRT) to analyze the psychometric properties of the SAHD and identify an abbreviated version of the scale. Data were drawn from 4 studies of psychological distress at the end of life. Participants were 1,076 patients diagnosed with either advanced cancer or AIDS. The sample was divided into 2 subsamples for scale analysis and development of the shortened form. IRT was used to estimate item parameters. A 6-item version of the SAHD (SAHD-A) was identified through examination of item parameter estimations. The SAHD-A demonstrated adequate convergent validity. Receiver operating characteristic analyses indicated comparable cut scores to identify patients with high levels of DHD. These analyses support the utility of the SAHD-A, which can be more easily integrated into research studies and clinical assessments of DHD. (PsycINFO Database Record PMID- 27280745 TI - Individuals at high risk for suicide are categorically distinct from those at low risk. AB - Although suicide risk is often thought of as existing on a graded continuum, its latent structure (i.e., whether it is categorical or dimensional) has not been empirically determined. Knowledge about the latent structure of suicide risk holds implications for suicide risk assessments, targeted suicide interventions, and suicide research. Our objectives were to determine whether suicide risk can best be understood as a categorical (i.e., taxonic) or dimensional entity, and to validate the nature of any obtained taxon. We conducted taxometric analyses of cross-sectional, baseline data from 16 independent studies funded by the Military Suicide Research Consortium. Participants (N = 1,773) primarily consisted of military personnel, and most had a history of suicidal behavior. The Comparison Curve Fit Index values for MAMBAC (.85), MAXEIG (.77), and L-Mode (.62) all strongly supported categorical (i.e., taxonic) structure for suicide risk. Follow up analyses comparing the taxon and complement groups revealed substantially larger effect sizes for the variables most conceptually similar to suicide risk compared with variables indicating general distress. Pending replication and establishment of the predictive validity of the taxon, our results suggest the need for a fundamental shift in suicide risk assessment, treatment, and research. Specifically, suicide risk assessments could be shortened without sacrificing validity, the most potent suicide interventions could be allocated to individuals in the high-risk group, and research should generally be conducted on individuals in the high-risk group. (PsycINFO Database Record PMID- 27280744 TI - Factor structure of the Perceived Stress Scale-10 (PSS) across English and Spanish language responders in the HCHS/SOL Sociocultural Ancillary Study. AB - Despite widespread use, psychometric investigation of the original English and translated Spanish versions of the 10-item Perceived Stress Scale (PSS; Cohen, Kamarck, & Mermelstein, 1983) has been limited among the U.S. Hispanic/Latino population. The present study examined the factor structure, factorial invariance, and reliability and validity of PSS scores from English and Spanish versions using data from 5,176 Hispanics/Latinos who participated in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. The total sample and language multigroup confirmatory factor analyses supported a bifactor model with all 10 PSS items loading on a general perceived stress factor, and the 4 reverse-worded items also loading on a reverse-worded factor. Internal consistency ranged from .68 to .78, and it was indicated that reliable variance exists beyond the general perceived stress factor. The model displayed configural, metric, scalar, and residual invariance across language groups. Convergent validity analyses indicated that both the general perceived stress factor and the reverse-worded factor were related to scores of depression, anxiety, and anger in the expected directions. The reverse-worded factor added to the validity of the PSS beyond the general perceived stress factor. The total computed score of the PSS can be recommended for use with Hispanics/Latinos in the United States that complete the measure in English or Spanish and the reverse worded factor can enhance prediction. (PsycINFO Database Record PMID- 27280746 TI - Rasch analysis of the Rosenberg Self-Esteem Scale with African Americans. AB - Effectively diagnosing African Americans' self-esteem has posed an unresolved challenge. To address this assessment issue, we conducted exploratory factor analysis and Rasch analysis to assess the psychometric characteristics of the Rosenberg Self-Esteem Scale (RSES, Rosenberg, 1965) for African American college students. The dimensional structure of the RSES was first identified with the first subsample (i.e., calibration subsample) and then held up under cross validation with a second subsample (i.e., validation subsample). Exploratory factor analysis and Rasch analysis both supported unidimensionality of the measure, with that finding replicated for a random split of the sample. Response scale use was generally appropriate, items were endorsed at a high level reflecting high levels of self-esteem, and person separation and reliability of person separation were adequate, and reflected results similar to those found in prior research. However, as some categories were infrequently used, we also collapsed scale points and found a slight improvement in scale and item indices. No differential item functioning was found by sex or having received professional assistance versus not; there were no mean score differences by age group, marital status, or year in college. Two items were seen as problematic. Implications for theory and research on multicultural mental health are discussed. (PsycINFO Database Record PMID- 27280747 TI - Systematic Review: Early Infant Feeding and the Risk of Type 1 Diabetes. AB - BACKGROUND: In addition to genetic background, a number of environmental factors have been claimed to influence the development of type 1 diabetes (T1D), including infant diet. OBJECTIVE: The aim of the study was to systematically update evidence on the possible relation between early feeding practices and the risk of T1D. METHODS: The Cochrane Library, MEDLINE, EMBASE, Web of Science, and CINAHL were searched for studies of any design up to July 2015. MEDLINE and EMBASE were additionally searched in March 2016. The primary outcome measures were the development of T1D or T1D-associated autoimmunity (T1DA). RESULTS: Nine publications were identified. Breastfeeding at the time of gluten introduction, as compared to gluten introduction after weaning, did not reduce the risk of developing T1DA or T1D. In children at high risk of developing T1D, except for gluten introduction at 3 months or younger age compared with gluten introduction at older than 3 months, which increased the risk of T1DA, the age of gluten introduction in infants had no effect on the risk of developing T1DA. CONCLUSIONS: Current evidence, mainly from observational studies, does not support the claim that early infant feeding practices, such as breastfeeding at gluten introduction or the age of the infant at the time of gluten introduction, may decrease the risk of developing T1D. More robust data are needed from randomized controlled trials. PMID- 27280749 TI - HLA-B*44 May Be a Marker for Orofacial Granulomatosis. PMID- 27280750 TI - Correction to Stochastic On-Chip Detection of Subpicomolar Concentrations of Silver Nanoparticles. PMID- 27280748 TI - Are Expectations Too High for Transitioning Adolescents With Inflammatory Bowel Disease? Examining Adult Medication Knowledge and Self-Management Skills. AB - OBJECTIVE: Transition readiness assessment has focused attention on adolescent knowledge and skills, but data-driven benchmarks have not been established. METHODS: Patients with inflammatory bowel disease (IBD), ages 25 to 50 years, attending an outpatient gastroenterology clinic, were recruited to complete a voluntary, confidential survey asking patients to recall medications and potential side effects, and to rate their degree of independence performing health maintenance tasks. RESULTS: The 141 respondents (48% response rate) had mean age of 36 years with median disease duration of 11 years. They were 60% female, 54% had Crohn disease, and 23% were diagnosed before age 18. Nearly all patients were fully independent answering doctor's questions during the visit (93%) and scheduling office visits (92%). Excluding pharmacy pick up, full independence seen in only 57%, whereas 16% significantly delegated tasks. No differences by sex, disease type, medication class, age at disease onset, or disease duration were found across levels of self-management. Almost all (97%) respondents could recall medication name, whereas fewer were able to recall dose (63%) or frequency (65%). Side effect knowledge was poor; among 81 patients on a biologic or immunomodulator, only 17 (21%) cited cancer and 22 (27%) cited infection. CONCLUSIONS: Adolescent IBD transition programs now have empirical data from the present study about adult benchmarks for independence in self management skills. Further research can establish which skills correlate with medication adherence and active collaboration with the medical team. The present study also exposes important gaps in medication risk knowledge and may allow improved patient education for subgroups of adult patients with IBD. PMID- 27280752 TI - A Novel Surgical Approach to Coracoid-based Eosinophilic Granuloma and the Technical Trick. AB - The coracoid base is a very rare location for tumors. It is difficult to diagnose and approach, but easy to dismiss. In this case, the tumor (eosinophilic granuloma of the scapula) was located at the base of the coracoid, and the posterior cortex was eroded by the tumor. Accessing this lesion through the deltopectoral approach with coracoid osteotomy without penetrating the supposed tumor extending posterior soft tissue will be discussed. This approach gives a wider and safer access to the surgeon than the posterior approach. This report presents a customized solution with the deltopectoral approach, and the chevron type osteotomy to access the coracoid base and tension band wiring to fix the osteotomy side. PMID- 27280751 TI - Adequacy of Mental Health Services for HIV-Positive Patients with Depression: Ontario HIV Treatment Network Cohort Study. AB - BACKGROUND: Major depression can profoundly impact clinical and quality-of-life outcomes of people living with HIV, and this disease is underdiagnosed and undertreated in many HIV-positive individuals. Here, we describe the prevalence of publicly funded primary and secondary mental health service use and antidepressant use, as well as mental health care for depression in accordance with existing Canadian guidelines for HIV-positive patients with depression in Ontario, Canada. METHODS: We conducted a prospective cohort study linking data from the Ontario HIV Treatment Network Cohort Study with administrative health databases in the province of Ontario, Canada. Current depression was assessed using the Center for Epidemiologic Depression Scale or the Kessler Psychological Distress Scale. Multivariable regressions were used to characterize prevalence outcomes. RESULTS: Of 990 HIV-positive patients with depression, 493 (50%) patients used mental health services; 182 (18%) used primary services (general practitioners); 176 (18%) used secondary services (psychiatrists); and 135 (14%) used both. Antidepressants were used by 407 (39%) patients. Patients who identified as gay, lesbian, or bisexual, as having low income or educational attainment, or as non-native English speakers or immigrants to Canada were less likely to obtain care. Of 493 patients using mental health services, 250 (51%) received mental health care for depression in accordance with existing Canadian guidelines. CONCLUSIONS: Our results showed gaps in delivering publicly funded mental health services to depressed HIV-positive patients and identified unequal access to these services, particularly among vulnerable groups. More effective mental health policies and better access to mental health services are required to address HIV-positive patient needs and reduce depression's impact on their lives. PMID- 27280753 TI - Osteochondral Autograft Transfer for Treatment of Metacarpophalangeal and Interphalangeal Cartilage Defects. AB - There is no general consensus regarding the optimal surgical treatment for cartilage defects of the metacarpophalangeal and interphalangeal joints in active patients who wish to preserve motion and functionality. We describe our technique of arthroscopically harvested femoral osteochondral autograft for treatment of metacarpophalangeal and interphalangeal cartilage defects. PMID- 27280754 TI - A Novel Technique for Correcting Extensor Lag in Vascularized Toe PIP Joint Transfers. AB - The use of the vascularized second-toe proximal interphalangeal joint (PIPJ) for vascularized joint transfers (VJTs) allows for restoration of powerful pinch/grasp and range of movement of a PIPJ in the hand. However, because of the lack of central slip formation in the majority of toes, the reconstructed PIPJ often results in extension lag. Extension lag associated with poor central slip formation in the lesser toes can be corrected using central slip reconstruction methods such as the Stack method. However, such methods are often cumbersome and involve extensive dissection and soft tissue manipulation. We present a novel, reproducible, simple yet effective technique in recreating the insertion point of the extensor tendon in the reconstructed finger, hence correcting the issue of extensor lag in vascularized toe joint transfers. The crux of this technique empowers the surgeon with the ability to correct inherent extensor lag of toes in VTJs. This will hence nullify "toe PIPJ angles" as a preselection criteria in determining patients suitable for VJT, thus enabling more patients to benefit from VJTs. PMID- 27280755 TI - Nanoshell Assembly for Magnet-Responsive Oil-Degrading Bacteria. AB - The modified polyelectrolyte-magnetite nanocoating was applied to functionalize the cell walls of oil decomposing bacteria Alcanivorax borkumensis. Cationic coacervate of poly(allylamine) and 20 nm iron oxide nanoparticles allowed for a rapid single-step encapsulation process exploiting electrostatic interaction with bacteria surfaces. The bacteria were covered with rough 70-100-nm-thick shells of magnetite loosely bound to the surface through polycations. This encapsulation allowed for external manipulations of A. borkumensis with magnetic field, as demonstrated by magnetically facilitated cell displacement on the agar substrate. Magnetic coating was naturally removed after multiple cell proliferations providing next generations of the cell in the native nonmagnetic form. The discharged biosurfactant vesicles indicating the bacterial functionality (150 +/- 50 nm lipid micelles) were visualized with atomic force microscopy in the bacterial biofilms. PMID- 27280756 TI - Sphenoid Wing Dysplasia with Pulsatile Exophthalmos in Neurofibromatosis Type 1. PMID- 27280764 TI - The Impact of Glyphosate, Its Metabolites and Impurities on Viability, ATP Level and Morphological changes in Human Peripheral Blood Mononuclear Cells. AB - The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide-glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis (phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01-10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis (phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances. PMID- 27280769 TI - Unlocking the Origin of Superior Performance of a Si-Ge Core-Shell Nanowire Quantum Dot Field Effect Transistor. AB - The sustained advancement in semiconducting core-shell nanowire technology has unlocked a tantalizing route for making next generation field effect transistor (FET). Understanding how to control carrier mobility of these nanowire channels by applying a gate field is the key to developing a high performance FET. Herein, we have identified the switching mechanism responsible for the superior performance of a Si-Ge core-shell nanowire quantum dot FET over its homogeneous Si counterpart. A quantum transport approach is used to investigate the gate field modulated switching behavior in electronic current for ultranarrow Si and Si-Ge core-shell nanowire quantum dot FETs. Our calculations reveal that for the ON state, the gate-field induced transverse localization of the wave function restricts the carrier transport to the outer (shell) layer with the pz orbitals providing the pathway for tunneling of electrons in the channels. The higher ON state current in the Si-Ge core-shell nanowire FET is attributed to the pz orbitals that are distributed over the entire channel; in the case of Si nanowire, the participating pz orbital is restricted to a few Si atoms in the channel resulting in a smaller tunneling current. Within the gate bias range considered here, the transconductance is found to be substantially higher in the case of a Si-Ge core-shell nanowire FET than in a Si nanowire FET, which suggests a much higher mobility in the Si-Ge nanowire device. PMID- 27280768 TI - Leishmania major Promastigotes Evade LC3-Associated Phagocytosis through the Action of GP63. AB - The protozoan Leishmania parasitizes macrophages and evades the microbicidal consequences of phagocytosis through the inhibition of phagolysosome biogenesis. In this study, we investigated the impact of this parasite on LC3-associated phagocytosis, a non-canonical autophagic process that enhances phagosome maturation and functions. We show that whereas internalization of L. major promastigotes by macrophages promoted LC3 lipidation, recruitment of LC3 to phagosomes was inhibited through the action of the parasite surface metalloprotease GP63. Reactive oxygen species generated by the NOX2 NADPH oxidase are necessary for LC3-associated phagocytosis. We found that L. major promastigotes prevented, in a GP63-dependent manner, the recruitment of NOX2 to phagosomes through a mechanism that does not involve NOX2 cleavage. Moreover, we found that the SNARE protein VAMP8, which regulates phagosomal assembly of the NADPH oxidase NOX2, was down-modulated by GP63. In the absence of VAMP8, recruitment of LC3 to phagosomes containing GP63-deficient parasites was inhibited, indicating that VAMP8 is involved in the phagosomal recruitment of LC3. These findings reveal a role for VAMP8 in LC3-associated phagocytosis and highlight a novel mechanism exploited by L. major promastigotes to interfere with the host antimicrobial machinery. PMID- 27280770 TI - Erratum: Vesicular Galectin-3 levels decrease with donor age and contribute to the reduced osteo-inductive potential of human plasma derived extracellular vesicles. PMID- 27280771 TI - Alpha 5 Integrin Mediates Osteoarthritic Changes in Mouse Knee Joints. AB - Osteoarthritis (OA) is one of most common skeletal disorders and can affect synovial joints such as knee and ankle joints. alpha5 integrin, a major fibronectin receptor, is expressed in articular cartilage and has been demonstrated to play roles in synovial joint development and in the regulation of chondrocyte survival and matrix degradation in articular cartilage. We hypothesized that alpha5 integrin signaling is involved in pathogenesis of OA. To test this, we generated compound mice that conditionally ablate alpha5 integrin in the synovial joints using the Gdf5Cre system. The compound mice were born normally and had an overall appearance similar to the control mice. However, when the mutant mice received the OA surgery, they showed stronger resistance to osteoarthritic changes than the control. Specifically the mutant knee joints presented lower levels of cartilage matrix and structure loss and synovial changes and showed stronger biomechanical properties than the control knee joints. These findings indicate that alpha5 integrin may not be essential for synovial joint development but play a causative role in induction of osteoarthritic changes. PMID- 27280772 TI - Transfer and Decontamination of S. aureus in Transmission Routes Regarding Hands and Contact Surfaces. AB - Hand hygiene, cleaning and disinfection are pre-requirements for hygiene management in hospital settings and the food industry. In order to facilitate risk management, different contamination scenarios and interventions need to be evaluated. In the present study data on transfer rates and reductions of Staphylococcus aureus were provided in an experimental set-up using artificial skin. Using this methodology, test persons were not exposed with pathogenic bacteria. An exposure assessment model was developed and applied to evaluate different contamination routes and hygiene interventions. The transfer rates of S. aureus from inoculated VITRO-SKIN(r) to fomites were calculated from blotting series. The VITRO-SKIN(r) was more prone to spread bacteria than fomites. When different surfaces were cleaned, the reduction of S. aureus varied between <1 and 7 log CFU. It could not be concluded that a certain coupon material, cleaning agent, cleaning wipe, soiling or humidity consistently resulted in a high or low reduction of S. aureus. The reduction of S. aureus and E. coli during hand washing was evaluated on artificial skin, VITRO-SKIN(r). The reduction of E. coli on VITRO-SKIN(r) was similar to the log reduction obtained when washing human hands. The S. aureus count on a human hand was both calculated in different scenarios describing different contamination routes starting from a contaminated hand using the exposure assessment model, and measured on an experimental setup using VITRO-SKIN(r) for validation. A linear relationship was obtained between the analysed level of S. aureus and the calculated level. However, the calculated levels of S. aureus on the VITRO-SKIN(r) in the scenarios were 1-1.5 log lower than the analysed level. One of the scenarios was used to study the effect of interventions like hand washing and cleaning of surfaces. PMID- 27280773 TI - Correction: Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01. AB - [This corrects the article DOI: 10.1371/journal.pone.0147211.]. PMID- 27280774 TI - Correction: Dredging in the Spratly Islands: Gaining Land but Losing Reefs. AB - [This corrects the article DOI: 10.1371/journal.pbio.1002422.]. PMID- 27280775 TI - Who Shall Not Be Treated: Public Attitudes on Setting Health Care Priorities by Person-Based Criteria in 28 Nations. AB - The principle of distributing health care according to medical need is being challenged by increasing costs. As a result, many countries have initiated a debate on the introduction of explicit priority regulations based on medical, economic and person-based criteria, or have already established such regulations. Previous research on individual attitudes towards setting health care priorities based on medical and economic criteria has revealed consistent results, whereas studies on the use of person-based criteria have generated controversial findings. This paper examines citizens' attitudes towards three person-based priority criteria, patients' smoking habits, age and being the parent of a young child. Using data from the ISSP Health Module (2011) in 28 countries, logistic regression analysis demonstrates that self-interest as well as socio-demographic predictors significantly influence respondents' attitudes towards the use of person-based criteria for health care prioritization. This study contributes to resolving the controversial findings on person-based criteria by using a larger country sample and by controlling for country-level differences with fixed effects models. PMID- 27280776 TI - Magnetic Resonance Imaging of Alimentary Tract Development in Manduca sexta. AB - Non-invasive 3D magnetic resonance imaging techniques were used to investigate metamorphosis of the alimentary tract of Manduca sexta from the larval to the adult stage. The larval midgut contracts in volume immediately following cessation of feeding and then greatly enlarges during the late pharate pupal period. Magnetic resonance imaging revealed that the foregut and hindgut of the pharate pupa undergo ecdysis considerably earlier than the external exoskeleton. Expansion of air sacs in the early pupa and development of flight muscles several days later appear to orient the midgut into its adult position in the abdomen. The crop, an adult auxiliary storage organ, begins development as a dorsal outgrowth of the foregut. This coincides with a reported increase in pupal ecdysteroid titers. An outgrowth of the hindgut, the rectal sac, appears several days later and continues to expand until it nearly fills the dorsal half of the abdominal cavity. This development correlates with a second rise in pupal ecdysteroid titers. In the pharate pupa, the presence of paramagnetic species renders the silk glands hyperintense. PMID- 27280777 TI - Amphipathic beta2,2-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia pneumoniae. AB - We demonstrate in the current work that small cationic antimicrobial beta2,2 amino acid derivatives (Mw < 500 Da) are highly potent against Chlamydia pneumoniae at clinical relevant concentrations (< 5 MUM, i.e. < 3.4 MUg/mL). C. pneumoniae is an atypical respiratory pathogen associated with frequent treatment failures and persistent infections. This gram-negative bacterium has a biphasic life cycle as infectious elementary bodies and proliferating reticulate bodies, and efficient treatment is challenging because of its long and obligate intracellular replication cycle within specialized inclusion vacuoles. Chlamydicidal effect of the beta2,2-amino acid derivatives in infected human epithelial cells was confirmed by transmission electron microscopy. Images of infected host cells treated with our lead derivative A2 revealed affected chlamydial inclusion vacuoles 24 hours post infection. Only remnants of elementary and reticulate bodies were detected at later time points. Neither the EM studies nor resazurin-based cell viability assays showed toxic effects on uninfected host cells or cell organelles after A2 treatment. Besides the effects on early intracellular inclusion vacuoles, the ability of these beta2,2-amino acid derivatives to suppress Chlamydia pneumoniae infectivity upon treatment of elementary bodies suggested also a direct interaction with bacterial membranes. Synthetic beta2,2-amino acid derivatives that target C. pneumoniae represent promising lead molecules for development of antimicrobial agents against this hard-to-treat intracellular pathogen. PMID- 27280779 TI - Researchers Are Curious Creatures: Message From the President. PMID- 27280778 TI - Mechanism of Mitochondrial Transcription Factor A Attenuation of CpG-Induced Antibody Production. AB - Mitochondrial transcription factor A (TFAM) had previously been shown to act as a damage associated molecular pattern with the ability to enhance CpG-A phosphorothioate oligodeoxynucleotide (ODN)-mediated stimulation of IFNalpha production from human plasmacytoid dendritic cells. Examination of the mechanism by which TFAM might influence CpG ODN mediated innate immune responses revealed that TFAM binds directly, tightly and selectively to the structurally related CpG A, -B, and -C ODN. TFAM also modulated the ability of the CpG-B or -C to stimulate the production of antibodies from human B cells. TFAM showed a dose dependent modulation of CpG-B, and -C -induced antibody production from human B cells in vitro, with enhancement of high dose and inhibition of low doses of CpG stimulation. This effect was linked to the ability of TFAM to directly inhibit the binding of CpG ODNs to B cells, in a manner consistent with the relative binding affinities of TFAM for the ODNs. These data suggest that TFAM alters the free concentration of the CpG available to stimulate B cells by sequestering this ODN in a TFAM-CpG complex. Thus, TFAM has the potential to decrease the pathogenic consequences of exposure to natural CpG-like hypomethylated DNA in vivo, as well as such as that found in traumatic injury, infection, autoimmune disease and during pregnancy. PMID- 27280780 TI - Improving motorcycle conspicuity through innovative headlight configurations. AB - Most motorcycle crashes involve another vehicle that violated the motorcycle's right-of-way at an intersection. Two kinds of perceptual failures of other road users are often the cause of such accidents: motorcycle-detection failures and motion-perception errors. The aim of this study is to investigate the effect of different headlight configurations on motorcycle detectability when the motorcycle is in visual competition with cars. Three innovative headlight configurations were tested: (1) standard yellow (central yellow headlight), (2) vertical white (one white light on the motorcyclist's helmet and two white lights on the fork in addition to the central white headlight), and (3) vertical yellow (same configuration as (2) with yellow lights instead of white). These three headlight configurations were evaluated in comparison to the standard configuration (central white headlight) in three environments containing visual distractors formed by car lights: (1) daytime running lights (DRLs), (2) low beams, or (3) DRLs and low beams. Video clips of computer-generated traffic situations were displayed briefly (250ms) to 57 drivers. The results revealed a beneficial effect of standard yellow configuration and the vertical yellow configuration on motorcycle detectability. However, this effect was modulated by the car-DRL environment. Findings and practical recommendations are discussed with regard to possible applications for motorcycles. PMID- 27280781 TI - Patterns of recurrence and treatment in male breast cancer: A clue to prognosis? AB - Male breast cancer (MBC) patients seem to have inferior survival compared to female (FBC) ones, which is not fully explained by usual prognostic factors. Recurrence analysis could show differences in relapse patterns and/or in patients' approaches that justify these outcomes. Retrospective analysis of MBC patients treated in a cancer center between 1990 and 2014, looking for relapse. For each patient, three matched FBC patients were selected by: diagnosis' year, age (within 5 years), stage and tumors' type (only luminal-like were considered). Differences between cohorts were assessed by chi(2) test and hierarchical clustering was performed to define subgroups according to relapse local. Survival curves were calculated by Kaplan-Meier and compared using log-rank test. Statistical significance was defined as p < 0.05. Groups were balanced according to age, histological grade, stage, expression of hormonal receptors and adjuvant treatments. Median time to recurrence was equivalent, p = 0.72, with the majority of patients presented with distant metastases, p = 0.69, with more lung involvement in male, p = 0.003. Male patients were more often proposed to symptomatic treatment (21.1% vs. 4.4%, p = 0.02). Overall and from recurrence survivals were poorer for male, median: 5 years [95% confidence interval (CI): 4.1-5.9 years] and 1 year (95% CI: 0-2.1 years) vs. 10 years (95% CI: 7.8-12.2 years) and 2 years (95% CI: 1.6-2.4 years), p < 0.001 and p = 0.004, respectively, and this tendency remained in the five cluster subgroups, that identified five patterns of relapse, p = 0.003. MBC patients had the worst survival, even after controlling important factors, namely the local of relapse. Palliative systemic treatment had favorable impact in prognosis and its frequently avoidance in male could justify the outcomes differences. PMID- 27280782 TI - Predicting Postoperative Morbidity and Readmission for Revision Posterior Lumbar Fusion. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The primary aim of this study was to determine the incidence and risk factors for 30-day adverse events after revision posterior lumbar fusion. The secondary aim was to determine the incidence and risk factors for 30-day readmission after revision posterior lumbar fusion. SUMMARY OF BACKGROUND DATA: The need for revision of a lumbar fusion is an unfortunate occurrence, and there is little known about specific risk factors for morbidity and readmission after this procedure. The purpose of this study is to use a large, national sample to identify patient and operative factors that may contribute to the development of these adverse outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was used to identify patients undergoing revision posterior lumbar fusion from 2005 to 2013. Patient characteristics were tested for association with any adverse event (AAE), severe adverse events (SAEs), minor adverse events (MAEs), and readmission within 30 days postoperatively using multivariate analysis. RESULTS: Of the 1287 patients identified, 8.2% had an AAE, 5.6% had an SAE, and 3.2% had an MAE. AAE was independently associated with American Society of Anesthesiologists (ASA) classification >=3 and operative time >=310 minutes (P<0.05 for each). SAEs were associated with only ASA classification >=3 (P=0.047). MAEs were associated with insulin-dependent diabetes, operative time >=310 minutes, and 3 or more levels of fusion (P<0.05 for all).Sixty-five patients (5.6%) were readmitted. On multivariate analysis, body mass index (BMI) 25-30, BMI 30-35, BMI>=35, ASA classification >=3, insulin dependent diabetes, a 2-level fusion, and 3 or more levels of fusion were associated with readmission (P<0.05 for all). CONCLUSIONS: In general, longer, more extensive procedures on sicker patients were associated with increased risk of postoperative complications and readmission. PMID- 27280783 TI - Patterns of Neurological Recovery After Anterior Decompression With Fusion and Posterior Decompression With Laminoplasty for the Treatment of Multilevel Cervical Spondylotic Myelopathy. AB - STUDY DESIGN: The pattern of neurological recovery in the overall modified Japanese Orthopedic Association scores, upper limb function score, and lower limb function score after surgical decompression for patients suffering from multilevel cervical spondylotic myelopathy (CSM) were analyzed in this independent retrospective study. OBJECTIVE: The primary objective of this retrospective study was to compare the upper and lower limb function changes after anterior decompression with fusion versus posterior decompression with laminoplasty for patients suffering from multilevel CSM. An additional objective was to describe the neural recovery speed. SUMMARY OF BACKGROUND DATA: Few comparative studies have been conducted to evaluate the outcome of anterior versus posterior surgery in multilevel CSM. However, these assessments tend to be of a more global perspective, looking at a composite score for upper limb, lower limb, and bladder function. No reports have separately analyzed the upper and lower limb function changes after anterior and posterior decompression for multilevel CSM. MATERIALS AND METHODS: A total of 132 patients were classified into anterior and posterior decompression groups based on the different surgical approach they underwent. The pattern of neurological recovery in the overall modified Japanese Orthopedic Association scores, upper limb function score, and lower limb function score after surgical decompression were documented and analyzed. RESULTS: There was no significant difference in the overall neurological recovery between anterior and posterior decompression groups. But in terms of the upper or lower limb function changes after operation, it appeared that the upper limbs recovered better with anterior decompression. The surgical approach did not significantly alter lower extremity recovery potential. In addition, most of the neurological recovery occurred in the first 9 months after surgical decompression. CONCLUSIONS: We recommend a individualized approach when it is difficult to determine an anterior or posterior surgery for multilevel CSM. Rehabilitation training should be carried out as early as possible. PMID- 27280784 TI - Surgical Treatment of Thoracic Spinal Cord Herniation. AB - Thoracic spinal cord herniation (TSCH) is an unusual condition characterized by central displacement of the spinal cord through a dural defect, resulting in neurological impairment due to compression and vascular compromise. Different surgical techniques have been described to treat symptomatic patients with TSCH such as closure of the defect by primary sutures after reducing the spinal cord, widening the dural defect to prevent cord strangulation, or reducing the spinal cord and using a dural patch. Through a case presentation of a 62-year-old woman with TSCH, we describe step-by-step, a surgical technique for repair by reducing the spinal cord and using a dural patch. In our experience surgical reduction of the hernia will frequently improve the patient's symptoms and signs even in patients with longstanding deficits. The final objective of this surgical technique is to prevent recurrent herniation and progressive deficit. PMID- 27280785 TI - Fluorescence Probe Based on Hybrid Mesoporous Silica/Quantum Dot/Molecularly Imprinted Polymer for Detection of Tetracycline. AB - A newly designed fluorescence probe made from a hybrid quantum dot/mesoporous silica/molecularly imprinted polymer (QD/MS/MIP) was successfully created, and the probe was used for the detection of tetracycline (TC) in serum sample. QD/MS/MIP was characterized by transmission electron microscope, Fourier transform infrared spectroscopy, UV spectroscopy, X-ray powder diffraction, nitrogen adsorption-desorption experiment and fluorescence spectroscopy. Tetracycline, which is a type of broad-spectrum antibiotic, was selected as the template. The monomer and the template were combined by covalent bonds. After the template was removed to form a binding site, a hydrogen bonding interaction formed between the hole and the target molecule. Moreover, when rebinding TC, a new complex was produced between the amino group of QD/MS/MIP and the hydroxyl group of TC. After that, the energy of the QDs could transfer to the complex, which explains the fluorescence quenching phenomenon. The fluorescent intensity of QD/MS/MIP decreased in 10 min, and an excellent linearity from 50 to 1000 ng mL(-1) was correspondingly obtained. This composite material has a high selectivity with an imprinting factor of 6.71. In addition, the confirmed probe strategy was successfully applied to serum sample analyses, and the recoveries were 90.2%-97.2% with relative standard deviations of 2.2%-5.7%. This current work offers a novel and suitable method to synthesize QD/MS/MIP with a highly selective recognition ability. This composite material will be valuable for use in fluorescence probe applications. PMID- 27280786 TI - Identification of Functional Domains in the Cohesin Loader Subunit Scc4 by a Random Insertion/Dominant Negative Screen. AB - Cohesin is a multi-subunit complex that plays an essential role in genome stability. Initial association of cohesin with chromosomes requires the loader-a heterodimer composed of Scc4 and Scc2 However, very little is known about the loader's mechanism of action. In this study, we performed a genetic screen to identify functional domains in the Scc4 subunit of the loader. We isolated scc4 mutant alleles that, when overexpressed, have a dominant negative effect on cell viability. We defined a small region in the N terminus of Scc4 that is dominant negative when overexpressed, and on which Scc2/Scc4 activity depends. When the mutant alleles are expressed as a single copy, they are recessive and do not support cell viability, cohesion, cohesin loading or Scc4 chromatin binding. In addition, we show that the mutants investigated reduce, but do not eliminate, the interaction of Scc4 with either Scc2 or cohesin. However, we show that Scc4 cannot bind cohesin in the absence of Scc2 Our results provide new insight into the roles of Scc4 in cohesin loading, and contribute to deciphering the loading mechanism. PMID- 27280787 TI - A Combination of CRISPR/Cas9 and Standardized RNAi as a Versatile Platform for the Characterization of Gene Function. AB - Traditional loss-of-function studies in Drosophila suffer from a number of shortcomings, including off-target effects in the case of RNA interference (RNAi) or the stochastic nature of mosaic clonal analysis. Here, we describe minimal in vivo GFP interference (miGFPi) as a versatile strategy to characterize gene function and to conduct highly stringent, cell type-specific loss-of-function experiments in Drosophila miGFPi combines CRISPR/Cas9-mediated tagging of genes at their endogenous locus with an immunotag and an exogenous 21 nucleotide RNAi effector sequence with the use of a single reagent, highly validated RNAi line targeting this sequence. We demonstrate the utility and time effectiveness of this method by characterizing the function of the Polymerase I (Pol I)-associated transcription factor Tif-1a, and the previously uncharacterized gene MESR4, in the Drosophila female germline stem cell lineage. In addition, we show that miGFPi serves as a powerful technique to functionally characterize individual isoforms of a gene. We exemplify this aspect of miGFPi by studying isoform specific loss-of-function phenotypes of the longitudinals lacking (lola) gene in neural stem cells. Altogether, the miGFPi strategy constitutes a generalized loss of-function approach that is amenable to the study of the function of all genes in the genome in a stringent and highly time effective manner. PMID- 27280789 TI - Diagnostic-driven antifungal therapy in neutropenic patients using the D-index and serial serum galactomannan testing. AB - INTRODUCTION: Invasive mold disease is an important complication of patients with hematologic malignancies, and is associated with high mortality. A diagnostic driven approach has been an alternative to the classical empiric antifungal therapy. In the present study we tested an algorithm that incorporated risk stratification using the D-index, serial serum galactomannan and computed tomographic-scan to guide the decision to start antifungal therapy in neutropenic patients. PATIENTS AND METHODS: Between May 2010 and August 2012, patients with acute leukemia in induction remission were prospectively monitored from day 1 of chemotherapy until discharge or death with the D-index and galactomannan. Patients were stratified in low, intermediate and high risk according to the D index and an extensive workup for invasive mold disease was performed in case of positive galactomannan (>=0.5), persistent fever, or the appearance of clinical manifestations suggestive of invasive mold disease. RESULTS: Among 29 patients, 6 (21%), 11 (38%), and 12 (41%) were classified as high, intermediate, and low risk, respectively. Workup for invasive mold disease was undertaken in 67%, 73% and 58% (p=0.77) of patients in each risk category, respectively, and antifungal therapy was given to 67%, 54.5%, and 17% (p=0.07). Proven or probable invasive mold disease was diagnosed in 67%, 45.5%, and in none (p=0.007) of high, intermediate, and low risk patients, respectively. All patients survived. CONCLUSION: A risk stratification using D-index was a useful instrument to be incorporated in invasive mold disease diagnostic approach, resulting in a more comprehensive antifungal treatment strategy, and to guide an earlier start of treatment in afebrile patients under very high risk. PMID- 27280790 TI - Characteristics of gonorrhea and syphilis cases among the Roma ethnic group in Belgrade, Serbia. AB - BACKGROUND: The Roma ethnic group is the largest and most marginalized minority in Europe, believed to be vulnerable to sexually transmitted infections. AIM: The purpose of the study was to investigate frequency and characteristics of gonorrhea and syphilis among the Roma population in Belgrade. METHODS: Data from the City Institute for Skin and Venereal Diseases to which all gonorrhea and syphilis cases are referred were analyzed. RESULTS: During the period of 2010 2014 sexually transmitted infections were more frequent among Roma than in rest of Belgrade population. Average percentages of Roma among all reported subjects with syphilis and those with gonorrhea were 9.6% and 13.5%, respectively, while the percentage of Roma in the total Belgrade population was about 1.6%. Roma with syphilis and gonorrhea were more frequently men (75%), most frequently aged 20-29 years (43.4%), never married (64.5%), with elementary school or less (59.2%), unemployed (80.3%), and heterosexual (89.5%). Among Roma 10.5% were sex workers and 68.4% did not know the source of their infection. Significant differences between Roma cases and other cases in Belgrade in all characteristics observed were in agreement with differences between Roma population and the total population of Serbia. CONCLUSION: The present study confirmed the vulnerability of the Roma population to sexually transmitted infections. PMID- 27280788 TI - Synthetic Physical Interactions Map Kinetochore-Checkpoint Activation Regions. AB - The spindle assembly checkpoint (SAC) is a key mechanism to regulate the timing of mitosis and ensure that chromosomes are correctly segregated to daughter cells. The recruitment of the Mad1 and Mad2 proteins to the kinetochore is normally necessary for SAC activation. This recruitment is coordinated by the SAC kinase Mps1, which phosphorylates residues at the kinetochore to facilitate binding of Bub1, Bub3, Mad1, and Mad2. There is evidence that the essential function of Mps1 is to direct recruitment of Mad1/2. To test this model, we have systematically recruited Mad1, Mad2, and Mps1 to most proteins in the yeast kinetochore, and find that, while Mps1 is sufficient for checkpoint activation, recruitment of either Mad1 or Mad2 is not. These data indicate an important role for Mps1 phosphorylation in SAC activation, beyond the direct recruitment of Mad1 and Mad2. PMID- 27280791 TI - Methicillin-resistant Staphylococcus aureus isolates from surfaces and personnel at a hospital laundry facility. AB - AIM: Examine a clinical laundry facility for the presence of methicillin resistant Staphylococcus aureus (MRSA) on environmental surfaces and among personnel. METHODS: Nasal and face samples along with surface samples were collected four times in 2015. MRSA isolates were confirmed using standardized biochemical assays and molecular characterization. RESULTS: MRSA was identified in 33/120 (28%) samples from the dirty and 3/120 (3%) samples from the clean environmental areas. MRSA isolates included: (dirty) ST5 SCCmec type II, ST8 SCCmec type IV, ST231 SCCmec type II, ST239 SCCmec type III, ST239 SCCmec type IV, ST256 SCCmec type IV and (clean) ST5 SCCmec type II and ST8 SCCmec type IV. Five different employees were MRSA positive, 4/8 (50%) from the dirty: and 1/15 (6.7%) from the clean, but there was a 10-fold higher MRSA carriage 6/22 (27%) dirty vs 1/38 (2.6%) clean when all 50 human samples were combined. CONCLUSION: MRSA prevalence was significantly higher (28 vs 3%) in dirty vs clean areas within the laundry facility suggesting a greater risk for personnel on the dirty side. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of isolation and characterization of MRSA from surfaces and personnel from a clinical laundry facility. PMID- 27280793 TI - Withdrawn: Current approach for the diagnosis of Aplastic Anemia. AB - Withdrawn by the publisher. PMID- 27280792 TI - Uncomplicated Clinical Malaria Features, the Efficacy of Artesunate-Amodiaquine and Their Relation with Multiplicity of Infection in the Democratic Republic of Congo. AB - BACKGROUND: In the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the multiplicity of infection in children with uncomplicated malaria. METHODS: Children aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and multiplicity of infection (MOI). RESULTS: In total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8-58.8) and 92.8% (95%CI: 91.0-94.6) respectively, as 83.6% (95%CI: 79.1-87.2) of the recurrences were new infections. Compared to monoclonal infections, polyclonal infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20-2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7-6.7) decreased to 3 (IQR: 1-5) in the recurrent samples (p<0.001). Patients infected with a single haplotype on day 0 had no recrudescence; the risk of recrudescence increased by 28% with each additional haplotype (HR: 1.3, 95%CI: 1.24-1.44). CONCLUSION: The PCR-corrected efficacy of ASAQ at day 42 was 92.8%, but crude efficacy was relatively poor due to high reinfection rates. Treatment outcomes were positively correlated with MOI. Continued monitoring of the efficacy of ACTs ASAQ, in this case-is paramount. TRIAL REGISTRATION: ClinicalTrials.gov NCT01374581. PMID- 27280794 TI - Evolving Treatment Algorithms in Crohn's Disease. AB - BACKGROUND: Crohn's disease (CD) is a chronic, disabling and destructive condition. Half of patients will develop some bowel damage (stricture, fistula and/or abscess). Current therapeutic strategies failed to alter its natural history. OBJECTIVE: We explore in a review article the evolution of CD treatment over a quarter of a century from a linear sequence of treatment intensification to a complex algorithm focused on individualized patient care by looking beyond symptoms. Specifically we focus on evolving concepts in assessing disease severity, selecting rigorous treatment end-targets, initiating an effective therapeutic therapy, and managing secondary loss of response. RESULTS: A tight monitoring of objective signs of inflammation and a treat-to-target approach are probably the only way to change patients' life and disease course. We now seek to optimize our therapeutic tools according to patient profile, disease phenotype and the unique pharmacodynamics that ensues. CONCLUSION: Standardizing the clinical practice of gastroenteroogists with the most current treatment algorithm may minimize disease related complications while favouring patient's quality of life. PMID- 27280795 TI - Non Coding RNAs: A New Avenue for the Self-Tailoring of Blood Cancer Treatment. AB - Hematological malignancies, accounting for about 10% of all deaths for cancer, include various forms of leukemia, lymphoma and myeloma. At present, hematological malignancies are analyzed and classified on the basis of morphologic characteristics, cell surface markers, cytogenetic aberrations and molecular markers. Unfortunately, in most cases, standard criteria are not sufficient for both an early diagnosis and a complete classification. The latter issue hampers an optimal therapeutic choice for these patients that often display heterogeneous clinical outcomes or responses to therapy. This heterogeneity has determined a need for improved methods of analysis and novel markers for diagnosis and classification of these malignancies. Non coding RNAs act as master regulators of numerous biological processes including epigenetic response, apoptosis and cell cycle. The recent advances in cancer research have led to a spreading out in the clinical use of genomic information; in fact, several studies are investigating the prominent role of both miRNAs and lncRNAs in hematopoietic differentiation and proliferation, as well as in the development of various hematological malignancies. These investigations are mainly aimed at researching new therapeutic opportunities that could boost a reduced risk of adverse events in normal tissues. Moreover, not less important, there is also a growing interest in determining how ncRNAs are associated with clinical features. In this review we focus on the aberrant ncRNAs expression in the most common forms of blood cancers, each of which exhibits a unique signature in comparison to normal counterparts. In addition to their regulatory role and in virtue of the well known ncRNAs' capacity of modulating signal and pathway networks, herein we discuss both miRNAs' and lncRNAs' potential as new powerful biomarkers for efficient diagnosis and prediction of response for patients with hematological malignancies. PMID- 27280796 TI - Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis. AB - : : Chronic liver injury from various causes often results in liver fibrosis (LF). Although the liver possesses endogenous tissue-repairing activities, these can be overcome by sustained inflammation and excessive fibrotic scar formation. Advanced LF leads to irreversible cirrhosis and subsequent liver failure and/or hepatic cancer. Here, using the mouse carbon tetrachloride (CCl4)-induced LF model, we showed that a single intravenous administration of stem cells derived from human exfoliated deciduous teeth (SHEDs) or of SHED-derived serum-free conditioned medium (SHED-CM) resulted in fibrotic scar resolution. SHED-CM suppressed the gene expression of proinflammatory mediators, such as TNF-alpha, IL-1beta, and iNOS, and eliminated activated hepatic stellate cells by inducing their apoptosis, but protected parenchymal hepatocytes from undergoing apoptosis. In addition, SHED-CM induced tissue-repairing macrophages that expressed high levels of the profibrinolytic factor, matrix metalloproteinase 13. Furthermore, SHED-CM suppressed the CCl4-induced apoptosis of primary cultured hepatocytes. SHED-CM contained a high level of hepatocyte growth factor (HGF). Notably, HGF depleted SHED-CM (dHGF-CM) did not suppress the proinflammatory response or resolve fibrotic scarring. Furthermore, SHED-CM, but not dHGF-CM, inhibited CCl4 induced hepatocyte apoptosis. These results suggest that HGF plays a central role in the SHED-CM-mediated resolution of LF. Taken together, our findings suggest that SHED-CM provides multifaceted therapeutic benefits for the treatment of LF. SIGNIFICANCE: This study demonstrated that a single intravenous administration of stem cells from human exfoliated deciduous teeth (SHEDs) or of the serum-free conditioned medium (CM) derived from SHEDs markedly improved mouse liver fibrosis (LF). SHED-CM suppressed chronic inflammation, eliminated activated hepatic stellate cells by inducing their apoptosis, protected hepatocytes from undergoing apoptosis, and induced differentiation of tissue-repairing macrophages expressing high levels of the profibrinolytic factor matrix metalloproteinase 13. Furthermore, hepatocyte growth factor played a central role in the SHED-CM mediated resolution of LF. This is the first report demonstrating the multifaceted therapeutic benefits of secreted factors derived from SHEDs for LF. PMID- 27280797 TI - Bone Marrow Mesenchymal Stem Cell-Based Engineered Cartilage Ameliorates Polyglycolic Acid/Polylactic Acid Scaffold-Induced Inflammation Through M2 Polarization of Macrophages in a Pig Model. AB - : The regeneration of tissue-engineered cartilage in an immunocompetent environment usually fails due to severe inflammation induced by the scaffold and their degradation products. In the present study, we compared the tissue remodeling and the inflammatory responses of engineered cartilage constructed with bone marrow mesenchymal stem cells (BMSCs), chondrocytes, or both and scaffold group in pigs. The cartilage-forming capacity of the constructs in vitro and in vivo was evaluated by histological, biochemical, and biomechanical analyses, and the inflammatory response was investigated by quantitative analysis of foreign body giant cells and macrophages. Our data revealed that BMSC-based engineered cartilage suppressed in vivo inflammation through the alteration of macrophage phenotype, resulting in better tissue survival compared with those regenerated with chondrocytes alone or in combination with BMSCs. To further confirm the macrophage phenotype, an in vitro coculture system established by engineered cartilage and macrophages was studied using immunofluorescence, enzyme linked immunosorbent assay, and gene expression analysis. The results demonstrated that BMSC-based engineered cartilage promoted M2 polarization of macrophages with anti-inflammatory phenotypes including the upregulation of CD206, increased IL-10 synthesis, decreased IL-1beta secretion, and alterations in gene expression indicative of M1 to M2 transition. It was suggested that BMSC seeded constructs have the potential to ameliorate scaffold-induced inflammation and improve cartilaginous tissue regeneration through M2 polarization of macrophages. SIGNIFICANCE: Finding a strategy that can prevent scaffold-induced inflammation is of utmost importance for the regeneration of tissue-engineered cartilage in an immunocompetent environment. This study demonstrated that bone marrow mesenchymal stem cell (BMSC)-based engineered cartilage could suppress inflammation by increasing M2 polarization of macrophages, resulting in better tissue survival in a pig model. Additionally, the effect of BMSC-based cartilage on the phenotype conversion of macrophages was further studied through an in vitro coculture system. This study could provide further support for the regeneration of cartilage engineering in immunocompetent animal models and provide new insight into the interaction of tissue-engineered cartilage and macrophages. PMID- 27280798 TI - Stepwise Differentiation of Mesenchymal Stem Cells Augments Tendon-Like Tissue Formation and Defect Repair In Vivo. AB - : Tendon injuries are common and present a clinical challenge, as they often respond poorly to treatment and result in long-term functional impairment. Inferior tendon healing responses are mainly attributed to insufficient or failed tenogenesis. The main objective of this study was to establish an efficient approach to induce tenogenesis of bone marrow-derived mesenchymal stem cells (BMSCs), which are the most common seed cells in tendon tissue engineering. First, representative reported tenogenic growth factors were used as media supplementation to induce BMSC differentiation, and the expression of teno lineage transcription factors and matrix proteins was compared. We found that transforming growth factor (TGF)-beta1 significantly induced teno-lineage specific gene scleraxis expression and collagen production. TGF-beta1 combined with connective tissue growth factor (CTGF) elevated tenomodulin and Egr1 expression at day 7. Hence, a stepwise tenogenic differentiation approach was established by first using TGF-beta1 stimulation, followed by combination with CTGF for another 7 days. Gene expression analysis showed that this stepwise protocol initiated and maintained highly efficient tenogenesis of BMSCs. Finally, regarding in situ rat patellar tendon repair, tendons treated with induced tenogenic BMSCs had better structural and mechanical properties than those of the control group, as evidenced by histological scoring, collagen I and tenomodulin immunohistochemical staining, and tendon mechanical testing. Collectively, these findings demonstrate a reliable and practical strategy of inducing tenogenesis of BMSCs for tendon regeneration and may enhance the effectiveness of cell therapy in treating tendon disorders. SIGNIFICANCE: The present study investigated the efficiency of representative tenogenic factors on mesenchymal stem cells' tenogenic differentiation and established an optimized stepwise tenogenic differentiation approach to commit tendon lineage differentiation for functional tissue regeneration. The reliable tenogenic differentiation approach for stem cells not only serves as a platform for further studies of underlying molecular mechanisms but also can be used to enhance cell therapy outcome in treating tendon disorders and develop novel therapeutics for tendon injury. PMID- 27280800 TI - Seasonal Changes in Socio-Spatial Structure in a Group of Free-Living Spider Monkeys (Ateles geoffroyi). AB - Ecological and social factors influence individual movement and group membership decisions, which ultimately determine how animal groups adjust their behavior in spatially and temporally heterogeneous environments. The mechanisms behind these behavioral adjustments can be better understood by studying the relationship between association and space use patterns of groups and how these change over time. We examined the socio-spatial patterns of adult individuals in a free ranging group of spider monkeys (Ateles geoffroyi), a species with high fission fusion dynamics. Data comprised 4916 subgroup scans collected during 325 days throughout a 20-month period and was used to evaluate changes from fruit-scarce to fruit-abundant periods in individual core-area size, subgroup size and two types of association measures: spatial (core-area overlap) and spatio-temporal (occurrence in the same subgroup) associations. We developed a 3-level analysis framework to distinguish passive associations, where individuals are mostly brought together by resources of common interest, from active association, where individuals actively seek or avoid certain others. Results indicated a more concentrated use of space, increased individual gregariousness and higher spatio temporal association rates in the fruit-abundant seasons, as is compatible with an increase in passive associations. Nevertheless, results also suggested active associations in all the periods analyzed, although associations differed across seasons. In particular, females seem to actively avoid males, perhaps prompted by an increased probability of random encounters among individuals, resulting from the contraction of individual core areas. Our framework proved useful in investigating the interplay between ecological and social constraints and how these constraints can influence individual ranging and grouping decisions in spider monkeys, and possibly other species with high fission-fusion dynamics. PMID- 27280799 TI - Treatment With Human Wharton's Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction. AB - : The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton's jelly derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 * 10(6) WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68 positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor kappaB and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. SIGNIFICANCE: Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor kappaB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. PMID- 27280801 TI - Enhanced Expression of miR-199b-5p Promotes Proliferation of Pancreatic beta Cells by Down-Regulation of MLK3. AB - BACKGROUND: The initiation of beta-cell proliferation to recover reduced beta cell mass is considered as one of the attractive therapeutic approaches for type 1 and 2 diabetes. In this study, we investigated the involvement of miRNAs in beta-cell proliferation. METHODS: Global miRNA array analysis of pancreas tissue was carried out using a 60% partial pancreatectomy (PPx) rodent model, which is a well-characterized model for pancreatic regeneration with accelerated proliferation of beta-cells. To explore miRNAs with mitogenic activity on beta cells, precursors and antisense oligonucleotides (ASOs) for miRNAs were transfected into a primary islet monolayer cell cultures isolated from adult rats in order to modify their expression and proliferation of beta-cells. RESULTS: We found that miR-199b-5p, which was up-regulated 2.6 times in the pancreas of the PPx treated group, significantly enhanced the proliferation of beta-cells when its precursor was over-expressed. Target genes of miR-199b-5p were investigated and Mixed lineage kinase-3 (MLK3) was identified as one of the candidates since its expression was down-regulated through an interaction with miR-199b-5p and siRNA treatment for MLK3 enhanced the proliferation of beta-cells. CONCLUSION: Our data suggest that the up-regulation of miR-199b-5p enhances proliferation of beta-cells at least in part through down-regulation of MLK3. PMID- 27280802 TI - Three-Year Outcomes With the Multilayer Flow Modulator for Repair of Thoracoabdominal Aneurysms: A Follow-up Report From the STRATO Trial. AB - PURPOSE: To evaluate midterm outcomes of endovascular repair of types II and III thoracoabdominal aortic aneurysms (TAAA) using the Multilayer Flow Modulator (MFM) in patients unsuitable for open surgery or fenestrated stent-grafts. METHODS: In the prospective, multicenter, nonrandomized STRATO trial (EudraCT registration: 2009-013678-42; ClinicalTrials.gov identifier NCT01756911), 23 patients (mean age 75.8 years; 19 men) with Crawford type II and III TAAA (mean diameter 6.5 cm) were implanted between April 2010 and February 2011. Outcomes included all-cause mortality and stable aneurysm thrombosis with associated branch vessel patency. RESULTS: Through 36 months, there were 7 deaths (none confirmed as aneurysm-related), and no cases of spinal cord injury, device migration or fracture, or respiratory, renal, or peripheral complications. Three patients were lost to follow-up and 2 devices were explanted. The device was patent in the 11 remaining patients at 3 years. Stable aneurysm thrombosis was achieved for 15 of 20 patients at 12 months, 12 of 13 at 24 months, and 10 of 11 at 36 months. The rate of branch patency was 96% at 12 months (primary patency), 100% at 24 months, and 97% at 36 months. Nine patients suffered from endoleaks (attachment site or device overlap); 9 patients underwent 11 reinterventions (3 surgical). Maximum aneurysm diameter was stable for 18 of 20 patients at 12 months, 11 of 13 at 24 months, and 9 of 11 at 36 months. For 10 patients with computed tomography at 36 months, the mean ratio of aneurysm flow volume to total volume had decreased by 83%; the mean ratio of thrombus volume to total volume increased by 159%. CONCLUSION: Through 3 years, endovascular repair with the MFM appears to be safe and effective while successfully maintaining branch vessel patency. PMID- 27280803 TI - Dengue Vaccine: Considerations before Rollout in Colombia. PMID- 27280804 TI - Surface Chemistry of Nanoscale Mineralized Collagen Regulates Periodontal Ligament Stem Cell Fate. AB - The interplay between stem cells and their extracellular microenvironment is of critical importance to the stem cell-based therapeutics in regenerative medicine. Mineralized collagen is the main component of bone extracellular matrix, but the effect of interfacial properties of mineralized collagen on subsequent cellular behaviors is unclear. This study examined the role of surface chemistry of nanoscale mineralized collagen on human periodontal ligament stem cell (hPDLSC) fate decisions. The intrafibrillarly mineralized collagen (IMC), fabricated by a biomimetic bottom-up approach, showed a bonelike hierarchy with nanohydroxyapatites (HAs) periodically embedded within fibrils. The infrared spectrum of the IMC showed the presence of phosphate, carbonate, amide I and II bands; and infrared mapping displayed uniform and higher spatial distribution of mineralization in the IMC. However, the distribution of the phosphate group differed far from that of the amide I group in the extrafibrillarly mineralized collagen (EMC), in which flowerlike HA clusters randomly depositing around the surface of the fibrils. Moreover, a large quantity of extrafibrillar HAs covered up the C?O stretch and N-H in-plane bend, resulting in substantial reduction of amide I and II bands. Cell experiments demonstrated that the hPDLSCs seeded on the IMC exhibited a highly branched, osteoblast-like polygonal shape with extended pseudopodia and thick stress fiber formation; while cells on the EMC displayed a spindle shape with less branch points and thin actin fibril formation. Furthermore, the biocompatibility of EMC was much lower than that of IMC. Interestingly, even without osteogenic induction, mRNA levels of major osteogenic differentiation genes were highly expressed in the IMC during cultivation time. These data suggest that the IMC with a similar nanotopography and surface chemistry to natural mineralized collagen directs hPDLSCs toward osteoblast differentiation, providing a promising scaffold in bone tissue regeneration. PMID- 27280806 TI - Isolation and Purification of Ascorbate Oxidase from Acremonium sp. HI-25. AB - A screening test was undertaken to isolate microorganisms that produced ascorbate oxidase. The enzyme activity was found in a culture filtrate of a fungal strain (HI-25), newly isolated from a soil sample. Based on the morphological characteristics, this isolate was identified as Acremonium sp. From the examinations of cultural conditions, optimum conditions for enzyme production were found; strain HI-25 was aerobically cultured by a jar fermenter at 25 degrees C in a medium containing 5% glycerol, 2% defatted soybeans, 0.1% monosodium L-glutamate, 0.1% KH2PO4, 0.02% MgSO4 .7H2O, and 0.01% KCl, pH 6.0. After cultivation, an ascorbate oxidase was purified from the culture filtrate by an ammonium sulfate fractionation, column chromatographies on DEAE-cellulose and Butyl-Toyopearl, and gel filtration twice on Sephadex G-100. The purification was 850-fold with an activity yield of 8.8%. The purified enzyme gave a single band on SDS polyacrylamide gel electrophoresis, and had a molecular weight of 80,000 by SDS polyacrylamide gel electrophoresis and 76,000 by native gel filtration. This enzyme was most active at pH 4.0, 45 degrees C, and was most stable between pH 6.0-10.0 and at temperatures below 60 degrees C. PMID- 27280805 TI - Clinicopathological Study of Primary Intraosseous Squamous Cell Carcinoma of the Jaw and a Review of the Literature. AB - PURPOSE: Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant odontogenic tumor that originates from odontogenic epithelial remnants. It is often difficult to diagnose PIOSCC definitively; hence, extraction or surgical treatment is performed before the initial diagnosis in most cases. The present study examined new insights into and prognostic factors of patients with PIOSCC admitted to the authors' department. MATERIALS AND METHODS: An extensive record review was conducted of patients who underwent radical surgery for PIOSCC from January 2001 through December 2014. RESULTS: Of all cases of OSCC, the frequency of PIOSCC was 1.45%. The 2-year relapse-free survival (RFS) and overall survival (OS) rates were 50.0 and 41.6% in all cases, respectively. Three patients underwent surgery or tooth extraction before the initial diagnosis; in fact, intervention before initial diagnosis was found to be an important poor prognostic factor for RFS and OS. In contrast, patients who were not treated before the initial diagnosis was made did not exhibit any locoregional recurrence. CONCLUSIONS: The treatment of PIOSCC should be similar to that for oral cancer with at least clinical stage T3N0 in the National Comprehensive Cancer Network clinical practice guidelines. In addition, cases of PIOSCC that are not treated before the initial diagnosis are more likely to obtain a good prognosis. PMID- 27280807 TI - Production of a Novel Extracellular Polysaccharide by a Bacillus Strain Isolated from Soil. AB - A bacterium that was isolated from soil and identified as Bacillus circulans was found to produce a highly viscous extracellular polysaccharide when it was grown aerobically in a medium containing glucose as a sole source of carbon. The product was characterized by TLC and GC analyses as a novel heteropolysaccharide consisted of rhamnose, mannose, galactose, and mannuronic acid as sugar components. A maximal yield of polysaccharide reached about 2 g/liter by jar fermentor culture at 30 degrees C for 48 hr with a medium containing 1% glucose, 0.05% asparagine, 0.005% yeast extract, and small amounts of inorganic salts. Some culture conditions for the production of polysaccharide were investigated with flask culture; an optimal production was attained with a medium containing 0.1-1 % glucose and 0.01-0.05% asparagine, pH 7-8, at 30 degrees C under aerobic conditions. PMID- 27280808 TI - Dependence on the Preparation Procedure of the Polymorphism and Crystallinity of Chitosan Membranes. AB - Differences in the polymorphism and crystallinity of chitosan were found in membranes prepared by different procedures when examined by X-ray diffraction measurements for four samples of chitosan differing in the degree of polymerization. When an acetic acid solution of chitosan was dried in air and then soaked in an alkaline solution (method A), both hydrated and anhydrous polymorphs of chitosan were present in the resulting membranes; the latter polymorph made chitosan insoluble in common solvents of chitosan, and its crystallinity increased with decreasing chitosan molecular weight. When a highly concentrated chitosan solution in aqueous acetic acid was neutralized with an alkaline solution (method B), no anhydrous polymorphs were detected in the membrane because of incomplete drying. When aqueous formic acid was used as the solvent, behavior basically similar to that in aqueous acetic acid was observed. In contrast, even with method A, aqueous hydrochloric acid gave a chitosan membrane having very little anhydrous crystallinity. The crystalline polymorph called "1-2", which has been proposed to be one of four chitosan polymorphs, is considered to be a mixture of hydrated and anhydrous crystals. PMID- 27280809 TI - Change in the Contents of Arginine, Ornithine, and Urea in the Muscle of Marine Invertebrates Stored in Ice. AB - To investigate the usefulness of ornithine and urea as freshness indices for marine invertebrates, the muscle tissue from freshly caught samples was stored in ice for 15 days and the free amino acid concentration was measured. The total amount of free amino acids decreased slightly after 1 day in most of the samples. The arginine concentration also decreased in most of the samples, especially in kuro shrimp during ice storage, while the ornithine and urea levels increased markedly in arrow squid and kuro shrimp, and increased considerably in kuruma prawn. Based on these results, it is proposed to use urea and ornithine as freshness indices for kuro shrimp and arrow squid, while only urea is proposed for kuruma prawn. PMID- 27280810 TI - Effect of Tannins in Green Tea on the Urinary Methylguanidine Excretion in Rats Indicating a Possible Radical Scavenging Action. AB - The hydroxyl radical scavenging action of green tea tannin given orally to rats with experimental renal failure was examined by using the urinary methylguanidine excretion as an index. In rats given 2 mg of a green tea tannin mixture, the urinary methylguanidine excretion was significantly decreased or had a tendency to decrease. (-)-Epigallocatechin 3-O-gallate, the predominant component of the green tea tannin mixture, effected a decrease in the urinary methylguanidine excretion in rats at a dose as low as 0.25 mg, suggesting a hydroxyl radical scavenging action. PMID- 27280811 TI - Enzymatic Properties of Two Calcium-stimulated ATPases in the Neutral and Acidic pH Regions Found in the Membrane Fraction of Human Milk. AB - Two calcium-stimulated ATPases at optimal pH values of 5.0 and 7.0, which are designated as acid and neutral Ca(2+) -ATPase, respectively, were found in the membrane fraction of human milk, and their enzymatic properties were studied. For maximal activity, neutral Ca(2+)-ATPase required 0.45 mM Ca ion, while acid Ca(2+) -ATPase required 207 mM Ca ion. Neutral Ca(2+) -ATPase activity was not enhanced by adding the Mg ion at more than 0.1 mM. Among the nucleotides, neutral Ca(2+) -ATPase showed a higher substrate specificity to GTP, CTP, ITP, and UTP than to ATP, while ATP was the best substrate for acid Ca(2+) -ATPase. Neutral and acid Ca(2+) -ATPases had apparent Km values of 0.361 and 0.192 mM, and Vmax of 186 and 178 MUmol ATP hydrolyzed/mg of protein per min, respectively. Both Ca(2+) -ATPases were potently inhibited by fluoride, lanthanide, vanadate, and p chloromercuribenzoate, and inactivated by EDTA, EGTA, and CDTA, but were unaffected by N-ethylmaleimide, NaN3, ouabain, oxidized glutathione, or oligomycin, and were inactivated by heating at 60 degrees C for 10 min. These enzymes were concentrated in the membrane fraction of the cream and skim milk membrane. PMID- 27280812 TI - Nutritional Requirements in Multiple Auxotrophic Lactic Acid Bacteria: Genetic Lesions Affecting Amino Acid Biosynthetic Pathways in Lactococcus lactis, Enterococcus faecium, and Pediococcus acidilactici. AB - In a study of genetic lesions responsible for amino acid requirements in multiple auxotrophic lactic acid bacteria, a systematic attempt was made to isolate mutants that could synthesize each of the amino acids required by the parental strains of Lactococcus lactis, Enterococcus faecium, and Pediococcus acidilactici. After treatment with appropriate mutagens or, in some cases, spontaneously, such mutants could indeed be obtained with respect to many but not all essential amino acids. Successful isolation of mutants for a given amino acid means that a minor genetic lesion reparable by single-step mutations affects its biosynthesis; a failure to isolate mutants suggests the involvement of more extensive lesions. Analysis of the results obtained showed certain regularities: some of the biosynthetic pathways for individual amino acids were virtually unaffected or affected by minor lesions in all the strains tested, while others were affected to varying extents among the different strains. Further studies showed that the ability to synthesize a number of amino acids had been acquired simultaneously in several of the amino acid-synthesizing mutants obtained after a single-step mutagenesis in E. faecium and P. acidilactici. Some detailed analysis with one of such mutants from E. faecium showed that a structural alteration of RNA polymerase caused by a single-step mutation is to some extent associated with simultaneous acquisition of the synthetic ability for a number of amino acids. PMID- 27280813 TI - Effects of Phenolic Respiration Inhibitors on Cytochrome bc1 Complex of Rat-liver Mitochondria. AB - The respiration inhibitory effects of the inhibitory uncouplers, 2,6-diiodo-4 (2,2-dicyanovinyl)phenol and 2,6-dimethoxy-4-(2,2-dicyanovinyl)phenol, the binding site of which is cytochrome bc1 (cyt. bc1) complex, were studied with rat liver mitochondria. The inhibitory potency of 2,6-diiodo-4-(2,2 dicyanovinyl)phenol and of 2,6-dimethoxy-4-(2,2-dicyanovinyl)phenol was increased and decreased, respectively, by steep dissipation of the transmembrane electrical potential after adding the potent uncoupler, fluazinam, the uncoupling activity of which disappears with time. Changes in the inhibitory potency may have been due to variation of the binding affinity of these compounds to cyt. bc1 complex. Furthermore, the enhancement to the binding affinity of 2,6-diiodo-4-(2,2 dicyanovinyl)phenol was governed by the degree of reduction in the transmembrane electrical potential. These results suggest that the extent of conformational changes of cyt. bc1 complex, which resulted in an enhanced interaction between 2,6-diiodo-4-(2,2-dicyanovinyl)phenol and its binding niche, increased with decreasing transmembrane electrical potential. From examinations of the reduction of cyt. b, it is suggested that the action site of 2,6-diiodo-4-(2,2 dicyanovinyl)phenol may be close to or partially overlapping that of antimycin A. PMID- 27280814 TI - Effects of Organic Solvents on Streptomyces griseus Protease I with Transfer Action. AB - The protease I from Streptomyces griseus var. alcalophilus strongly catalyzed the transfer reaction forming hydroxamic acids of various amino acids, especially aromatic and hydrophobic amino acids. Dimethyl sulfoxide (DMSO), 1,4-butane diol, and glycerol protected this enzyme from heat denaturation. Moreover, only DMSO strongly activated the transfer action of protease I and the velocity of reaction was accelerated three times in the presence of 50% DMSO. The yield of transfer product strongly depended on reaction time and the concentrations of enzyme and substrates in the presence of DMSO. The velocity of the transfer reaction was faster than that of the hydrolysis reaction under the conditions of 0.1 M Phe OEt, 0.75 M NH2OH, and 50% DMSO. PMID- 27280815 TI - Scavenging of Active Oxygen Species by Glycated Proteins. AB - Scavenging of active oxygen species by glycated proteins was investigated. Glycated proteins were prepared from bovine serum albumin (BSA), insulin, and lysozyme incubated with glucose. Glycated BSA at concentration of 0.5% scavenged 34% of hydroxyl radicals by ESR experiments using DMPO as a spin-trapping reagent. The ability to scavenge hydroxyl radicals by glycated BSA was higher than that by BSA. Hydrogen peroxides also were largely scavenged with an increase in the concentration of glycated proteins. However, the ability to scavenge superoxides by glycated BSA was lower than that by BSA because glycated proteins produced superoxides. Experiments using model compounds such as Amadori compound and caproyl pyrraline suggested that the scavenging ability of glycated proteins against hydroxyl radicals depends on Maillard reaction products in the advanced stage, while the ability against hydrogen peroxides is dependent upon Maillard reaction products in the early stage and brown pigments. PMID- 27280816 TI - Spinnability of Starch Pastes. AB - We have developed apparatus to assess spinnability that uses an impedance to prevent of electrolysis. The spinning distance and the stress confirmed by measurement of dial gauge. A total of 10 starch pastes was prepared from corn, sago, katakuri, sweet potato, kuzu, edible canna, cassava, Indian lotus root, bracken, and potato, at 2% and 4% concentrations. The spinning distance of each starch paste showed a dependence on the concentration and the tensile velocity. The strain at the point of maximum stress increased in all samples with increases in the tensile velocity. The spinning energy increased with increase in the tensile velocity, with a particularly large dependence on the tensile velocity of potato. Cluster analysis was done using the spinning property values of 4% starch pastes as the parameters, which showed a division at a distance of 20, yielding four clusters, with each cluster showing a distinctive spinning pattern. PMID- 27280817 TI - Metabolism of (13)C-Isomaltooligosaccharides in Healthy Men. AB - Isomaltooligosaccharides (IMO), sweeteners derived from corn-starch, selectively promote the growth of bifidobacteria in the human intestine. The metabolic fate of IMO in healthy men was investigated. The expiration rates of excess (13)CO2 and hydrogen of six men were measured while sedentary and while taking physical exercise after the (13)C-labeled IMO intakes. The breath H2 excretion kept at a constant state after IMO ingestion in the sedentary test and increased in the exercise test. The serum glucose and serum insulin increased 30 min after IMO ingestion. The (13)CO2 recoveries were 28.7% in the sedentary test and 60.9% in the exercise test. These recoveries were 70-80% compared those of maltose. These results indicated that a part of IMO was digested and the residual IMO was fermented by intestinal flora. The energy value of IMO might be about 75% of that of maltose. PMID- 27280818 TI - Purification and Some Properties of an Erythrose Reductase from an Aureobasidium sp. Mutant. AB - An erythrose reductase was obtained from the cells of an Aureobasidium sp. mutant having high erythritol-producing activity. This enzyme was purified 600-fold over the cell-free extract by ammonium sulfate precipitation, ion exchange chromatography, affinity chromatography, and hydrophobic chromatography. It gave a single band on polyacrylamide gel electrophoresis, and had a molecular weight of 37,000 and an isoelectric point of 4.8. This enzyme had maximum reductive activity at 45 degrees C and pH 6.5. The optimum pH of the oxidative reaction was 9.5. It was stable at pH 6.0-8.0 and below 40 degrees C. The enzyme showed the maximum activity to D-erythrose. D-Glyceraldehyde was reduced at a rate 66% of that for D-erythrose. p-Nitrobenzaldehyde, L-erythrulose, dihydroxyacetone, and D glucuronate were also reduced, although at slower rates. The oxidative activity was less than 0.1% of the reductive one. PMID- 27280819 TI - An Alternate Synthesis of the Capsaicinoids. AB - Five capsaicinoids, the pungent ingredients of hot peppers, have been efficiently synthesized by a method involving the Wittig reaction between isobutyl triphenylphosphorane and the appropriate lactols (3), followed by the nitrous acid-induced isomerization of the resultant (Z)-olefins (4) to (E)-olefins (5). PMID- 27280820 TI - Formation of Ent-isophleichrome by Cladosporium herbarum Isolated from Sugar Beet. AB - An isolate of Cladosporium herbarum obtained from leaves of sugar beet produced a phytotoxic red pigment which was identified as ent-isophleichrome (1). Production of the pigment was dependent on composition of the culture medium. The toxicity of ent-isophleichrome to sugar beet was strongly influenced by light. The polyketide biosynthetic origin of ent-isophleichrome in C. herbarum was demonstrated by (13)C acetate labelling/(13)C NMR studies. PMID- 27280821 TI - Freezing and Ice Structure Formed in Protein Gels. AB - Ice structure was photographically analyzed for frozen soy protein curd and egg albumin gel frozen under various conditions. Dendritic ice structure was observed growing from the cooling plate parallel to the direction of the heat flux. The change in the ice structure size was analyzed at different locations from the cooling plate in the plane perpendicular to the direction of heat flux. In accordance with the theoretical relationship proposed by us before, the mean ice structure size was inversely proportional to the moving speed of the freezing front and the proportionality constant was not very much different from the diffusion coefficient of water, showing the important role of the molcular diffusion mechanism in the process of ice crystal growth. For the freezing accompanied with supercooling, the ice structure became very small, reflecting the very rapid moving speed of the freezing front when supercooling ceased. The theoretical model by us had advantages over the models proposed in the literature for its simple theoretical basis and wider applicability. PMID- 27280822 TI - Asymmetric Reduction of Acetophenone by Aspergillus Species and Their Possible Contribution to Katsuobushi Flavor. AB - Eight strains of Aspergillus species isolated from katsuobushi (dried bonito) were grown in a liquid medium containing acetophenone, to examine the possibility of asymmetric reduction of acetophenone during the molding process in katsuobushi production. Seven strains produced predominantly the R-stereoisomer of alpha phenethylalcohol. However, one strain gave the S-isomer predominantly. PMID- 27280823 TI - Changes of Dolichol and Dolichyl Fatty Ester Contents during Development of Soybean Seedlings. PMID- 27280824 TI - Cysteine-conjugate beta-Lyase from Mucor javanicus. PMID- 27280825 TI - Inhibition by Bovine Lactoferrin of Adhesion of L929 Cells Cultured in Serum-free GIT Medium. PMID- 27280826 TI - Development of Analytical Method for Selective Detection of Cardenolides by High Performance Liquid Chromatography. PMID- 27280827 TI - Carrageenan(lambda); Inhibitor of the Dephosphorylation of Casein Phosphopeptides (CPPs) by Alkaline Phosphatase. PMID- 27280828 TI - Purification and Some Properties of a Carboxymethyl Cellulase from Coriolus versicolor. PMID- 27280829 TI - Purification and Properties of a Chitosanase from Pseudomonas sp. H-14. PMID- 27280830 TI - Simultaneous High-performance Liquid Chromatographic Measurement of Xanthurenic Acid and 3-Hydroxyanthranilic Acid in Urine. PMID- 27280831 TI - Isolation and Characterization of an Allergy Inhibitor from the Jelutong, Dyera costulata Hook. f. PMID- 27280832 TI - Identification of a Soybean Protein Producing IgE Antibodies in BALB/c Mice. PMID- 27280833 TI - Effect of Dietary Lysine on Endogenous Hyperlipidemia in Nephrotic Rats. PMID- 27280834 TI - Effects of Calmodulin and Calmodulin Antagonists on Neutral Ca(2+)-ATPase in the Membrane Fraction of Human Milk. PMID- 27280835 TI - Heavy Metal Uptake by Swollen Chitosan Beads. PMID- 27280836 TI - Isolation and Identification of 6-(3',3'-Dimethylallyloxy)-4-methoxy-5 methylphthalide from Alternaria porri. PMID- 27280837 TI - A Novel Laccase Inhibitor, N-Hydroxyglycine, Produced by Penicillium citrinum YH 31. PMID- 27280838 TI - Partial Benzoylation of Methyl beta-L-Arabinopyranoside. PMID- 27280839 TI - Preparation of Congou Black Tea from Stale Green Tea. PMID- 27280840 TI - The Cell Surface Glycoprotein of Haloarcula japonica TR-1. PMID- 27280841 TI - Synthesis of Both the Enantiomers of (E)-1-Ethyl-5-methyl-4-heptenyl Acetate (Quadrilure), the Aggregation Pheromone of Cathartus quadricollis, by Enzyme catalyzed Hydrolysis in an Acetone-Water Solvent System with Lipase. PMID- 27280842 TI - Simple Synthesis of a Diastereomeric Mixture of 2-(3',4'-Epoxy-4' methylcyclohexyl)-6-methyl-2,5-heptadiene, the Pheromone of the Green Stink Bug. PMID- 27280843 TI - Oryzalexin S, a Novel Stemarane-type Diterpene Rice Phytoalexin. PMID- 27280844 TI - (E)-2-Hexenyl Hexanoate, the Alarm Pheromone of the Bean Bug Riptortus clavatus (Heteroptera: Alydidae). PMID- 27280846 TI - Isolation of a thiol-dependent serine protease in peanut and investigation of its role in the complement and the allergic reaction. AB - A serine protease activity was detected in aqueous peanuts seeds extracts, partially purified and characterized as a thiol-dependent serine protease. The potential role of this proteolytic activity on allergic reaction to peanuts was prospected through complement activation studies in human plasma and serum, and MDCK cells to investigate a possible occludin degradation in tight junctions. The peanut protease activity induced the production of anaphylatoxins C3a and C5a, and of the terminal membrane attack complex SC5b-9 whatever the complement activation pathway. The protease activity was also involved in the partial digestion of occludin within tight junctions, with for result, an increase of the epithelial permeability to antigen absorption. PMID- 27280845 TI - Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice. AB - BACKGROUND: Complement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known. METHODS: C57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32%kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFalpha, and C5a. RESULTS: Chronic ethanol feeding increased expression of pro inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFalpha, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFalpha was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFalpha. CONCLUSION: Taken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding. PMID- 27280847 TI - Low-Temperature Processable Block Copolymers That Preserve the Function of Blended Proteins. AB - Low-temperature processable polymers have attracted increasing interest as ecological materials because of their reduced energy consumption during processing and suitability for making composites with heat-sensitive biomolecules at ambient temperature. In the current study, low-temperature processable biodegradable block copolymers were synthesized by ring-opening polymerization of l-lactide (LLA) using polyphosphoester as a macroinitiator. The polymer films could be processed under a hydraulic pressure of 35 MPa. The block copolymer films swelled in water because the polyphosphoester block was partially hydrated. Interestingly, the swelling ratio of the films changed with temperature. The pressure-induced order-to-disorder transition of the block copolymers was characterized by small-angle X-ray scattering; a crystallinity reduction in the block copolymers was observed after application of pressure. The crystallinity of the block copolymers was recovered after removing the applied pressure. The Young's modulus of the block copolymer films increased as the LLA unit content increased. Moreover, the modulus did not change after multiple processing cycles and the recyclability of the block copolymers was also confirmed. Finally, polymer films with embedded proteinase K as a model protein were prepared. The activity of catalase loaded into the polymer films was evaluated after processing at different temperatures. The activity of catalase was preserved when the polymer films were processed at room temperature but was significantly reduced after high-temperature processing. The suitability of low-temperature processable biodegradable polymers for making biofunctional composites without reducing protein activity was clarified. These materials will be useful for biomedical and therapeutic applications. PMID- 27280848 TI - National Variation in Caesarean Section Rates: A Cross Sectional Study in Ireland. AB - OBJECTIVE: Internationally, caesarean section (CS) rates are rising. However, mean rates of CS across providers obscure extremes of CS provision. We aimed to quantify variation between all maternity units in Ireland. METHODS: Two national databases, the National Perinatal Reporting System and the Hospital Inpatient Enquiry Scheme, were used to analyse data for all women delivering singleton births weighing >=500g. We used multilevel models to examine variation between hospitals in Ireland for elective and emergency CS, adjusted for individual level sociodemographic, clinical and organisational variables. Analyses were subsequently stratified for nullipara and multipara with and without prior CS. RESULTS: The national CS rate was 25.6% (range 18.2% ? 35.1%). This was highest in multipara with prior CS at 86.1% (range 6.9% ? 100%). The proportion of variation in CS that was attributable to the hospital of birth was 11.1% (95% CI, 6.0 ? 19.4) for elective CS and 2.9% (95% CI, 1.4 ? 5.6) for emergency CS, after adjustment. Stratifying across parity group, variation between hospitals was greatest for multipara with prior CS. Both types of CS were predicted by increasing age, prior history of miscarriage or stillbirth, prior CS, antenatal complications and private model of care. CONCLUSION: The proportion of variation attributable to the hospital was higher for elective CS than emergency CS suggesting that variation is more likely influenced by antenatal decision making than intrapartum decision making. Multipara with prior CS were particularly subject to variability, highlighting a need for consensus on appropriate care in this group. PMID- 27280851 TI - Dissecting endophytic lifestyle along the parasitism/mutualism continuum in Arabidopsis. AB - Mutualistic interactions between plants and fungi often occur in the rhizosphere, although examples exist where shoot-endophytes support host growth and increase resistance to pathogens and herbivores. Fungal endophytes which colonize their hosts without any visible disease symptoms have been recognized to be fundamental components of various ecosystems. Initial efforts have been taken to decipher the genetic basis of beneficial plant-fungus interactions and of lifestyle transitions. This review gives a short overview on well established experimental systems amenable to genetic manipulation and of known genome sequence for dissecting plant-fungal endophyte interactions with a special focus on Arabidopsis thaliana associations. PMID- 27280849 TI - Oxidative Stress Mediates the Antiproliferative Effects of Nelfinavir in Breast Cancer Cells. AB - The discovery of the anti-proliferative activity of nelfinavir in HIV-free models has encouraged its investigation as anticancer drug. Although the molecular mechanism by which nelfinavir exerts antitumor activity is still unknown, its effects have been related to Akt inhibition. Here we tested the effects of nelfinavir on cell proliferation, viability and death in two human breast cancer cell lines and in human normal primary breast cells. To identify the mechanism of action of nelfinavir in breast cancer, we evaluated the involvement of the Akt pathway as well as the effects of nelfinavir on reactive oxygen species (ROS) production and ROS-related enzymes activities. Nelfinavir reduced breast cancer cell viability by inducing apoptosis and necrosis, without affecting primary normal breast cells. The antitumor activity of nelfinavir was related to alterations of the cell redox state, coupled with an increase of intracellular ROS production limited to cancer cells. Nelfinavir treated tumor cells also displayed a downregulation of the Akt pathway due to disruption of the Akt-HSP90 complex, and subsequent degradation of Akt. These effects resulted to be ROS dependent, suggesting that ROS production is the primary step of nelfinavir anticancer activity. The analysis of ROS-producers and ROS-detoxifying enzymes revealed that nelfinavir-mediated ROS production was strictly linked to flavoenzymes activation. We demonstrated that ROS enhancement represents the main molecular mechanism required to induce cell death by nelfinavir in breast cancer cells, thus supporting the development of new and more potent oxidizing molecules for breast cancer therapy. PMID- 27280852 TI - Proinsulin-Transferrin Fusion Protein Exhibits a Prolonged and Selective Effect on the Control of Hepatic Glucose Production in an Experimental Model of Type 1 Diabetes. AB - An ideal basal insulin (INS) replacement therapy requires the distribution or action of exogenous INS to more closely mimic physiological INS in terms of its preferential hepatic action. In this paper, we introduce a novel strategy to exert liver-specific INS action by hepatic activation of INS's precursor, proinsulin (ProINS). We demonstrated the conversion of human ProINS-transferrin (Tf) fusion protein, ProINS-Tf, into an active and immuno-reactive form of INS-Tf in the liver via the slow Tf receptor mediated recycling pathway. ProINS-Tf displayed prolonged basal blood glucose lowering effects for up to 40 h in streptozotocin-induced type 1 diabetic mice following a single subcutaneous injection. The effect of ProINS-Tf on blood glucose levels was observed predominantly under fasting conditions, with little effect under free-feeding conditions. In addition, both the pyruvate tolerance assay in normal mice and the Akt-phosphorylation assay in H-4-II-E hepatoma cells indicated that the hepatic activated ProINS-Tf possessed a much longer effect on the control of hepatic glucose production than INS. These results indicated that ProINS-Tf may serve as an effective and safe hepatoselective INS analog to reduce the frequency of INS injections as well as avert severe hypoglycemia episodes and other side effects frequently encountered with long-acting INS therapeutics due to their peripheral action. PMID- 27280850 TI - Cost-effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema Treatment: Analysis From the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial. AB - IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) medicines have revolutionized diabetic macular edema (DME) treatment. A recent randomized clinical trial comparing anti-VEGF agents for patients with decreased vision from DME found that at 1 year aflibercept (2.0 mg) achieved better visual outcomes than repackaged (compounded) bevacizumab (1.25 mg) or ranibizumab (0.3 mg); the worse the starting vision, the greater the treatment benefit with aflibercept. However, aflibercept and ranibizumab, respectively, are approximately 31 and 20 times more expensive than bevacizumab. OBJECTIVE: To examine the incremental cost effectiveness ratios (ICERs) of aflibercept, bevacizumab, and ranibizumab for the treatment of DME. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of efficacy, safety, and resource utilization data at 1-year follow-up from the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial. Patients were enrolled from August 22, 2012, through August 28, 2013, and analysis was performed from August 21, 2014, through November 7, 2015. MAIN OUTCOMES AND MEASURES: The ICERs for all trial participants and subgroups with baseline vision of approximate Snellen equivalent 20/32 to 20/40 (better vision) and baseline vision of approximate Snellen equivalent 20/50 or worse (worse vision). One-year trial data were used to calculate cost-effectiveness for 1 year for the 3 anti-VEGF agents; mathematical modeling was then used to project 10 year cost-effectiveness results. RESULTS: The study included 624 participants (mean [SD] age, 60.6 [10.5] years; 45.7% female; 65.5% white), 209 in the aflibercept group, 207 in the bevacizumab group, and 208 in the ranibizumab group. For all participants, during 1 year, the ICERs of aflibercept and ranibizumab compared with bevacizumab were $1 110 000 per quality-adjusted life year (QALY) and $1 730 000 per QALY, respectively. During 10 years, they were $349 000 per QALY and $603 000 per QALY, respectively. Compared with ranibizumab, aflibercept's ICER was $648 000 per QALY at 1 year and $203 000 per QALY at 10 years. For the subgroup with worse baseline vision, the 10-year ICERs of aflibercept and ranibizumab compared with bevacizumab were $287 000 per QALY and $817 000 per QALY, respectively. In eyes with decreased vision from DME, treatment costs of aflibercept and ranibizumab would need to decrease by 69% and 80%, respectively, to reach a cost-effectiveness threshold of $100 000 per QALY compared with bevacizumab during a 10-year horizon; for the subgroup with worse baseline vision, the costs would need to decrease by 62% and 84%, respectively. CONCLUSIONS AND RELEVANCE: Aflibercept (2.0 mg) and ranibizumab (0.3 mg) are not cost-effective relative to bevacizumab for treatment of DME unless their prices decrease substantially. These results highlight the challenges that physicians, patients, and policymakers face when safety and efficacy results are at odds with cost-effectiveness results. PMID- 27280853 TI - Metamemory in a familiar place: The effects of environmental context on feeling of knowing. AB - Feeling-of-knowing (FOK) judgments are judgments of future recognizability of currently inaccessible information. They are known to depend both on the access to partial information about a target of retrieval and on the familiarity of the cue that is used as a memory probe. In the present study we assessed whether FOK judgments could also be shaped by incidental environmental context in which these judgments are made. To this end, we investigated 2 phenomena previously documented in studies on recognition memory-a context familiarity effect and a context reinstatement effect-in the procedure used to investigate FOK judgments. In 2 experiments, we found that FOK judgments increase in the presence of a familiar environmental context. The results of both experiments further revealed still higher FOK judgments when made in the presence of environmental context matching the encoding context of both cue and its associated target. The effect of context familiarity on FOK judgment was paralleled by an effect on the latencies of an unsuccessful memory search, but the effect of context reinstatement was not. Importantly, the elevated feeling of knowing in reinstated and familiar contexts was not accompanied by an increase in the accuracy of those judgments. Together, these results demonstrate that metacognitive processes are shaped by the overall volume of memory information accessed at retrieval, independently of whether this memory information is related to a cue, a target, or a context in which remembering takes place. (PsycINFO Database Record PMID- 27280854 TI - Effect of filtration flux on the development and operation of a dynamic membrane for anaerobic wastewater treatment. AB - Dynamic membrane represents a cost effective alternative to conventional membranes by employing fouling as a means of solid-liquid separation. This study evaluated the effects of initial flux on both development rate of dynamic membrane and bioreactor performance during two consecutive experiments. The dynamic membrane was developed over a 200 MUm mesh and the reactor was operated under anaerobic conditions. It was found that the effect of an initial higher applied flux on dynamic membrane development was more pronounced than mixed liquor suspended solid concentration inside the bioreactor. The development of the dynamic membrane was therefore positively associated with the applied flux. The rapid development of the dynamic membrane during the second experimental run at high initial fluxes and lower MLSS concentrations also affected the performance of the bioreactor in terms of more efficient COD removal and biogas production. A major shortcoming of applying higher initial applied flux was the formation of a denser and robust dynamic membrane layer that was resistant to applied hydraulic shear to control desired permeability and thus represented an obstacle in maintaining a long term operation with sustainable flux at lower transmembrane pressure (TMP). PMID- 27280855 TI - From ignorance to evidence? The use of programme evaluation in conservation: Evidence from a Delphi survey of conservation experts. AB - Persistent gaps in the evidence base regarding the performance of conservation policies has put pressure on the conservation policy field to adopt 'best practice' programme evaluation methods. These are methods that account for the counterfactual and are able to attribute causality between a conservation policy and specific observable environmental and social impacts. Despite this pressure, use of such methods continues to be rare. This paper uses the Delphi technique to provide the first systematic assessment of the reasons behind the apparent hesitation of conservation practitioners to adopt rigorous policy impact evaluation methods. The Delphi study consisted of two online questionnaires conducted on conservation policy experts. The results presented confirm that the use of rigorous impact evaluation methods in conservation is still very limited but this, crucially, is not because conservationists are ignorant of these methods or their advantages. In fact, considerable effort is being made to develop and improve evidence standards but these efforts have largely been thwarted by large financial and time related constraints that mean even elementary evaluations are hard to achieve. The results from this Delphi study allow us to provide more realistic recommendations on how impact evaluation studies can be more widely embraced and implemented in conservation practice. PMID- 27280856 TI - Removal of diethyl phthalate from water by ozone microbubbles in a pilot plant. AB - Ozone microbubbles (OMBs) were used to remove diethyl phthalate (DEP) from water in a pilot plant. The removal of DEP and the mineralization efficiency were investigated under various reaction conditions. The removal of DEP by OMBs was very effective at the high pH and high ozone generation rates. Almost complete mineralization of DEP could be achieved at the high pH. The contribution of OH was computed by using a hydroxyl radical scavenger (i.e. t-BuOH). In neutral and alkaline media, the reaction of DEP with OH dominated over its direct reaction with ozone. The overall oxidation reaction fitted a second-order kinetic model. The overall rate constant and the volumetric mass transfer coefficient of ozone slightly increased with increasing pH. The results indicate that the OMBs were efficient in terms of the reduction of concentration of DEP and its complete mineralization. PMID- 27280857 TI - Modelling mercury accumulation in minerogenic peat combining FTIR-ATR spectroscopy and partial least squares (PLS). PMID- 27280858 TI - Quenching of chlorophyll fluorescence induced by silver nanoparticles. AB - The interaction between chlorophyll (Chl) and silver nanoparticles (AgNPs) was evaluated by analyzing the optical behavior of Chl molecules surrounded by different concentrations of AgNPs (10, 60, and 100nm of diameter). UV-Vis absorption, steady state and time-resolved fluorescence measurements were performed for Chl in the presence and absence of these nanoparticles. AgNPs strongly suppressed the Chl fluorescence intensity at 678nm. The Stern-Volmer constant (KSV) showed that fluorescence suppression is driven by the dynamic quenching process. In particular, KSV was nanoparticle size-dependent with an exponential decrease as a function of the nanoparticle diameter. Finally, changes in the Chl fluorescence lifetime in the presence of nanoparticles demonstrated that the fluorescence quenching may be induced by the excited electron transfer from the Chl molecules to the metal nanoparticles. PMID- 27280859 TI - Assessment of gamma radiation exposure of beach sands in highly touristic areas associated with plutonic rocks of the Atticocycladic zone (Greece). AB - This study aims to evaluate the activity concentrations of 238U, 226Ra, 232Th, 228Th and 40K along beaches close to the plutonic rocks of the Atticocycladic zone that ranged from 15 to 628, 12-2292, 16-10,143, 14-9953 and 191-1192 Bq/kg respectively. A sample from island of Mykonos contained the highest 232Th content measured in sediments of Greece. The heavy magnetic fraction and the heavy non magnetic fraction as well as the total heavy fraction, were correlated with the concentrations of the measured radionuclides in the bulk samples. The heavy fractions seem to control the activity concentrations of 238U and 232Th of all the samples, showing some local differences in the main 238U and 232Th mineral carrier. Similar correlations have been found between 238U, 232Th content and rare earth elements concentrations. The measured radionuclides in the beach sands were normalized to the respective values measured in the granitic rocks, which at least in most cases are their most probable parental rocks, so as to provide data upon their enrichment or depletion. Since the Greek beaches are among the most popular worldwide the annual effective dose equivalent received due to sand exposure has been estimated and found to vary between 0.002 and 0.379 mSv y-1 for tourists and from 0.018 to 3.164 mSv y-1 for local people working on the beach. The values corresponding to ordinary sand samples are orders of magnitude lower than the limit of 1 mSv y-1, only in the case of heavy minerals-rich sands the dose could reach or exceed the recommended maximum limit. PMID- 27280860 TI - Cytocompatible, Photoreversible, and Self-Healing Hydrogels for Regulating Bone Marrow Stromal Cell Differentiation. AB - Photo-crosslinking and self-healing have received considerable attention for the design of intelligent materials. A novel photostimulated, self-healing, and cytocompatible hydrogel system is reported. A coumarin methacrylate crosslinker is synthesized to modify the polyacrylamide-based hydrogels. With the [2+2] cyclo addition of coumarin moieties, the hydrogels exhibit excellent self-healing capacity when they are exposed to light with wavelengths at 280 and 365 nm, respectively. To enhance cell compatibility, a poly (amidoamine) crosslinker is also synthesized. Variations in light exposure times and irradiation wavelengths are found to alter the self-healing property of the hydrogels. The hydrogels are shown to induce a regular cellular pattern. The hydrogels are used to regulate bone marrow stromal cells differentiation. The relative mRNA expressions are recorded to monitor the osteogenic differentiation of the cells. PMID- 27280861 TI - Regiocontrolled Oxidative C-C Coupling of Dienol Ethers and 1,3-Dicarbonyl Compounds. AB - A strategy for synthesis of gamma-alkylated enones through oxidative coupling of siloxydienes and 1,3-dicarbonyl compounds is reported. This method is an interrupted form of our formal [3 + 2] cycloaddition method reported previously. The present work excels in generating all-carbon quaternary centers via C-C bond formation at the remote gamma-site which is traditionally challenging to functionalize. Stereoselectivity and functional group tolerance are examined in complex systems. Double alkylation reactions are also described. PMID- 27280865 TI - Nonadiabatic Tunneling in Photodissociation of Phenol. AB - Using recently developed full-dimensional coupled quasi-diabatic ab initio potential energy surfaces including four electronic ((1)pipi, (1)pipi*, 1(1)pisigma*, and 2(1)pisigma*) states, the tunneling dynamics of phenol photodissociation via its first excited singlet state (S1 <- S0) is investigated quantum mechanically using a three-dimensional model. The lifetimes of several low-lying vibrational states are examined and compared with experiment. The deuteration of the phenoxyl hydrogen is found to dramatically increase the lifetime, attesting to the tunneling nature of the nonadiabatic dissociation. Importantly, it is shown that owing to the conical intersection topography tunneling in this system cannot be described in the standard adiabatic approximation, which eschews the geometric phase effect since the nonadiabatically computed lifetimes, validated by comparison with experiment, differ significantly from those obtained in that limit. PMID- 27280866 TI - De novo mutations in autosomal recessive congenital malformations. PMID- 27280867 TI - A knowledge base for tracking the impact of genomics on population health. AB - PURPOSE: We created an online knowledge base (the Public Health Genomics Knowledge Base (PHGKB)) to provide systematically curated and updated information that bridges population-based research on genomics with clinical and public health applications. METHODS: Weekly horizon scanning of a wide variety of online resources is used to retrieve relevant scientific publications, guidelines, and commentaries. After curation by domain experts, links are deposited into Web based databases. RESULTS: PHGKB currently consists of nine component databases. Users can search the entire knowledge base or search one or more component databases directly and choose options for customizing the display of their search results. CONCLUSION: PHGKB offers researchers, policy makers, practitioners, and the general public a way to find information they need to understand the complicated landscape of genomics and population health.Genet Med 18 12, 1312 1314. PMID- 27280868 TI - Reflux and Chronic Rhinosinusitis. PMID- 27280869 TI - Timing of percutaneous cholecystostomy tube removal: systematic review. AB - INTRODUCTION: Percutaneous cholecystostomy (PC) is an effective procedure to treat moderate or severe acute cholecystitis (AC) in high-risk patients. The ideal timing of the drainage removal is argued. The aim of this study is to analyze our experience and perform a systematic review about the ideal timing of a percutaneous cholecystostomy (PC) tube removal. EVIDENCE ACQUISITION: A web based literature search was performed and studies reporting the length of the catheter maintenance were analyzed. A regression analysis between the timing of tube removal and morbidity, mortality and disease recurrence was performed. Patients who underwent PC as definitive treatment of moderate or severe acute cholecystitis at our institution between 2011 to 2015 were analyzed. Clinical and technical success, morbidity, mortality and recurrence rates were retrospectively retrieved from a perspective database. EVIDENCE SYNTHESIS: The systematic review yield to analyze 50 studies. None of them focused exclusively on outcome measures in relation to PC tube duration. The timing of the drain removal varied from 2 to 193 days. Regression analyses showed no correlation between length of tube maintenance and the considered outcomes. We studied 35 patients. The median age was 78 (range 52-94) and 88.5% had an ASA score >=3. P-POSSUM estimated morbidity was 68.7% (range 34.3-99.0) and mortality was 15.8% (range 1.9-80.2). Clinical success was 97.1%. Procedure-related morbidity was 34.3%: 2 abscess, 1 bleeding, 1 biloma and 8 tube dislodgment. Biliary leakage was not observed. The observed 30-day overall mortality was 11.4%. The median follow-up was 16 months. Recurrence rate was 12.1%. CONCLUSIONS: PC is an effective procedure in high-risk patients with moderate or severe AC. At the moment there is no evidence whether the duration of PC tube may affect outcome. PMID- 27280870 TI - Robotic hepatectomies: advances and perspectives. AB - INTRODUCTION: Over recent years, minimally invasive hepatic resections have increasingly been reported in the literature. Even though hepatic surgery is still considered a challenge for surgeons due to its technical difficulties and high morbidity, the development and spread of robotic surgery has highlighted a new interest, which has induced a rapid dissemination of robotic approaches for hepatic pathologies. This article presents a systematic review of the literature regarding robotic hepatectomy in order to assess the safety and feasibility of robotic hepatic surgery. EVIDENCE ACQUISITION: All eligible studies in robotic liver surgery which were published between January 2001 and January 2016 were reviewed systematically. Only series of ten patients and more were chosen in order to consider the experience of high-volume centers. In case of multiple articles on the same centers, the study including the largest number of patients was considered for the study. Overall, 18 studies, involving a total of 572 robotic liver resection (RLR) were finally analyzed. EVIDENCE SYNTHESIS: All articles in this review demonstrate that robotic liver surgery must be performed by surgeons trained in open liver surgery and skilled in minimally invasive techniques. CONCLUSIONS: RLR and laparoscopic liver resection (LLR) were comparable in terms of safety, feasibility, and outcome for hepatectomies. However, RLR is more expensive than LLR. Further studies are required before any final conclusion can be drawn. PMID- 27280871 TI - Bariatric surgery and vitamin D: key messages for surgeons and clinicians before and after bariatric surgery. AB - Obesity is the most widespread nutritional problem globally. Bariatric surgery is the preeminent long-term obesity treatment. Bariatric procedures manipulate the intestines to produces malabsorption and/or restrict the size of the stomach. The most enduring bariatric procedure is the Roux-en-Y gastric bypass, which utilizes both restriction (small stomach pouch) and malabsorption (duodenum bypass). The in-vogue procedure is the vertical sleeve gastrectomy - resection of the greater curvature of the stomach (predominantly restrictive). Malabsorptive procedures function by decreasing nutrient absorption, primarily fat and fat-soluble nutrients (vitamins A, D, E, and K). Most studies of vitamin D status in bariatric surgery candidates reported a prevalence of over 50% vitamin D deficiency (<50 nmol/L), enduring post-operatively with one study reporting 65% deficient at 10 years post-bariatric surgery. Obesity is associated with chronic inflammation, which may contribute to adverse surgical outcomes, e.g. poor healing and infection. Since vitamin D deficiency is also associated with chronic inflammation, obese individuals with vitamin D deficiency have extraordinary risk of adverse surgical outcomes, particularly delayed wound healing and infection due to the role of vitamin D in re-epithelialization and innate immunity. When the risk of adverse surgical outcomes in obesity is combined with that of vitamin D deficiency, there is likely an additive or potentially a synergistic effect. Furthermore, deficiency in fat-soluble vitamins, such as vitamin D, is considered a metabolic complication of bariatric surgery. Thus, determining the vitamin D status of bariatric surgery candidates and amending it preoperatively may prove greatly beneficial acutely and lifelong. PMID- 27280872 TI - Elevation, Not Deforestation, Promotes Genetic Differentiation in a Pioneer Tropical Tree. AB - The regeneration of disturbed forest is an essential part of tropical forest ecology, both with respect to natural disturbance regimes and large-scale human mediated logging, grazing, and agriculture. Pioneer tree species are critical for facilitating the transition from deforested land to secondary forest because they stabilize terrain and enhance connectivity between forest fragments by increasing matrix permeability and initiating disperser community assembly. Despite the ecological importance of early successional species, little is known about their ability to maintain gene flow across deforested landscapes. Utilizing highly polymorphic microsatellite markers, we examined patterns of genetic diversity and differentiation for the pioneer understory tree Miconia affinis across the Isthmus of Panama. Furthermore, we investigated the impact of geographic distance, forest cover, and elevation on genetic differentiation among populations using circuit theory and regression modeling within a landscape genetics framework. We report marked differences in historical and contemporary migration rates and moderately high levels of genetic differentiation in M. affinis populations across the Isthmus of Panama. Genetic differentiation increased significantly with elevation and geographic distance among populations; however, we did not find that forest cover enhanced or reduced genetic differentiation in the study region. Overall, our results reveal strong dispersal for M. affinis across human-altered landscapes, highlighting the potential use of this species for reforestation in tropical regions. Additionally, this study demonstrates the importance of considering topography when designing programs aimed at conserving genetic diversity within degraded tropical landscapes. PMID- 27280873 TI - Seeing the Talker's Face Improves Free Recall of Speech for Young Adults With Normal Hearing but Not Older Adults With Hearing Loss. AB - PURPOSE: Seeing the talker's face improves speech understanding in noise, possibly releasing resources for cognitive processing. We investigated whether it improves free recall of spoken two-digit numbers. METHOD: Twenty younger adults with normal hearing and 24 older adults with hearing loss listened to and subsequently recalled lists of 13 two-digit numbers, with alternating male and female talkers. Lists were presented in quiet as well as in stationary and speech like noise at a signal-to-noise ratio giving approximately 90% intelligibility. Amplification compensated for loss of audibility. RESULTS: Seeing the talker's face improved free recall performance for the younger but not the older group. Poorer performance in background noise was contingent on individual differences in working memory capacity. The effect of seeing the talker's face did not differ in quiet and noise. CONCLUSIONS: We have argued that the absence of an effect of seeing the talker's face for older adults with hearing loss may be due to modulation of audiovisual integration mechanisms caused by an interaction between task demands and participant characteristics. In particular, we suggest that executive task demands and interindividual executive skills may play a key role in determining the benefit of seeing the talker's face during a speech-based cognitive task. PMID- 27280874 TI - Impact of the introduction of Non-invasive prenatal genetic testing on invasive tests: A single-center study in Japan. PMID- 27280877 TI - Message From the President. PMID- 27280876 TI - Message From the Editor. PMID- 27280878 TI - Schedule-at-a-Glance. PMID- 27280879 TI - Inundation and Fire Shape the Structure of Riparian Forests in the Pantanal, Brazil. AB - Inundation and fire can affect the structure of riparian vegetation in wetlands. Our aim was to verify if there are differences in richness, abundance, basal area, composition and topographic preference of woody species in riparian forests related to the fire history, flooding duration, or the interaction between both. The study was conducted in the riparian forests of the Paraguay River some of which were burned three times between 2001 and 2011. We sampled trees with a girth of at least 5 cm at breast height in 150 5 * 10 m plots (79 burned and 71 unburned). We also measured height of the flood mark and estimated the flooding duration of each plot. We performed Generalized Linear Mixed Models to verify differences in richness, basal area, and abundance of individuals associated to interaction of fire and inundation. We used an analysis of similarity (ANOSIM) and indicator species analysis to identify differences in composition of species and the association with burned and unburned area according to different levels of inundation. Finally, we used a hierarchical set of Generalized Linear Models (GLM), the so-called HOF models, to analyse each species' specific response to inundation based on topography and to determine their preferred optimal topographic position for both burned as well as unburned areas. Richness was positively associated with elevation only in burned areas while abundance was negatively influenced by inundation only in burned areas. Basal area was negatively associated with time of inundation independent of fire history. There were 15 species which were significant indicators for at least one combination of the studied factors. We found nine species in burned areas and 15 in unburned areas, with response curves in HOF models along the inundation gradient. From these, five species shifted their optimal position along the inundation gradient in burned areas. The interaction of fire and inundation did not appear to affect the basal area, but it did affect the richness, number of individuals, success of some species, and seemed to shape the boundary of these forests as shown by the difference in the positioning of these species along the inundation gradient. PMID- 27280880 TI - Correction: Inhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression. AB - [This corrects the article DOI: 10.1371/journal.pone.0153682.]. PMID- 27280881 TI - The Evolutionary Origins of Hierarchy. AB - Hierarchical organization-the recursive composition of sub-modules-is ubiquitous in biological networks, including neural, metabolic, ecological, and genetic regulatory networks, and in human-made systems, such as large organizations and the Internet. To date, most research on hierarchy in networks has been limited to quantifying this property. However, an open, important question in evolutionary biology is why hierarchical organization evolves in the first place. It has recently been shown that modularity evolves because of the presence of a cost for network connections. Here we investigate whether such connection costs also tend to cause a hierarchical organization of such modules. In computational simulations, we find that networks without a connection cost do not evolve to be hierarchical, even when the task has a hierarchical structure. However, with a connection cost, networks evolve to be both modular and hierarchical, and these networks exhibit higher overall performance and evolvability (i.e. faster adaptation to new environments). Additional analyses confirm that hierarchy independently improves adaptability after controlling for modularity. Overall, our results suggest that the same force-the cost of connections-promotes the evolution of both hierarchy and modularity, and that these properties are important drivers of network performance and adaptability. In addition to shedding light on the emergence of hierarchy across the many domains in which it appears, these findings will also accelerate future research into evolving more complex, intelligent computational brains in the fields of artificial intelligence and robotics. PMID- 27280883 TI - Magnetohydrodynamic Flow by a Stretching Cylinder with Newtonian Heating and Homogeneous-Heterogeneous Reactions. AB - This article examines the effects of homogeneous-heterogeneous reactions and Newtonian heating in magnetohydrodynamic (MHD) flow of Powell-Eyring fluid by a stretching cylinder. The nonlinear partial differential equations of momentum, energy and concentration are reduced to the nonlinear ordinary differential equations. Convergent solutions of momentum, energy and reaction equations are developed by using homotopy analysis method (HAM). This method is very efficient for development of series solutions of highly nonlinear differential equations. It does not depend on any small or large parameter like the other methods i. e., perturbation method, delta-perturbation expansion method etc. We get more accurate result as we increase the order of approximations. Effects of different parameters on the velocity, temperature and concentration distributions are sketched and discussed. Comparison of present study with the previous published work is also made in the limiting sense. Numerical values of skin friction coefficient and Nusselt number are also computed and analyzed. It is noticed that the flow accelerates for large values of Powell-Eyring fluid parameter. Further temperature profile decreases and concentration profile increases when Powell Eyring fluid parameter enhances. Concentration distribution is decreasing function of homogeneous reaction parameter while opposite influence of heterogeneous reaction parameter appears. PMID- 27280882 TI - Prevalence, Predictors, and Same Day Treatment of Positive VIA Enhanced by Digital Cervicography and Histopathology Results in a Cervical Cancer Prevention Program in Cameroon. AB - BACKGROUND: In 2007, the Cameroon Baptist Convention Health Services (CBCHS) implemented a screen-and-treat cervical cancer prevention program using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC). METHODS: We retrospectively analyzed 46,048 medical records of women who received care through the CBCHS Women's Health Program from 2007 through 2014 to determine the prevalence and predictors of positive VIA-DC, rates of same day treatment, and cohort prevalence of invasive cervical cancer (ICC). RESULTS: Of the 44,979 women who were screened for cervical cancer, 9.0% were VIA-DC-positive, 66.8% were VIA DC-negative, 22.0% were VIA-DC-inadequate (normal ectocervix, but portions of the transformation zone were obscured), and 2.2% were VIA-DC-uncertain (cervical abnormalities confounding VIA-DC interpretation). Risk factors significantly associated with VIA-DC-positive screen were HIV-positivity, young age at sexual debut, higher lifetime number of sexual partners, low education status and higher gravidity. In 2014, 31.1% of women eligible for cryotherapy underwent same day treatment. Among the 32,788 women screened from 2007 through 2013, 201 cases of ICC were identified corresponding to a cohort prevalence of 613 per 100,000. CONCLUSIONS: High rate of VIA-DC-positive screens suggests a significant burden of potential cervical cancer cases and highlights the need for expansion of cervical cancer screening and prevention throughout the 10 regions of Cameroon. VIA-DC-inadequate rates were also high, especially in older women, and additional screening methods are needed to confirm whether these results are truly negative. In comparison to similar screening programs in sub-Saharan Africa there was low utilization of same day cryotherapy treatment. Further studies are required to characterize possible program specific barriers to treatment, for example cultural demands, health system challenges and cost of procedure. The prevalence of ICC among women who presented for screening was high and requires further investigation. PMID- 27280884 TI - Impact of Universal Hepatitis B Vaccination on Prevalence, Infection-Associated Morbidity and Mortality, and Circulation of Immune Escape Variants in Russia. AB - METHODS: 6,217 sera samples collected from volunteers in six epidemiologically different regions of Russia were tested for serological and molecular markers of HBV infection. A mathematical model developed by the U.S. Centers for Disease Control and Prevention was used to estimate the effect of vaccination and birth dose coverage on the incidence of HB and adverse outcomes of infection. RESULTS: Prevalence of HBsAg in the study population varied from 1.2% to 8.2%; anti-HBc detection rates were 13.0-46.2%. HBsAg detection rates in epidemiologically significant cohorts were 0.6-10.5% in women of childbearing age; 0-2.4% in children <=5 years old; 1.9-8.1% in adults >=30 years old. Mathematical modeling demonstrated that the current 96.1-99.6% level of birth dose coverage increased the effectiveness of vaccination 10-21 times compared to 50% and 0% birth dose coverage scenarios. HBV DNA was detected in 63 sera samples. The frequency of amino acid substitutions in HBsAg was 38% (24/63). Only in 3% (2/63) the mutations were within the a-determinant of HBsAg (M133T and G145S, one case each). None of the identified mutations eluded HBsAg detection, since all these samples tested positive for HBsAg by commercial ELISA. CONCLUSION: Despite a significant decline in acute HB incidence after the introduction of universal vaccination, many undiagnosed potential sources of infection remain. Low prevalence of HBV immune escape variants is a favorable predictor of vaccine effectiveness in the future. PMID- 27280885 TI - The ESX-5 System of Pathogenic Mycobacteria Is Involved In Capsule Integrity and Virulence through Its Substrate PPE10. AB - Mycobacteria produce a capsule layer, which consists of glycan-like polysaccharides and a number of specific proteins. In this study, we show that, in slow-growing mycobacteria, the type VII secretion system ESX-5 plays a major role in the integrity and stability of the capsule. We have identified PPE10 as the ESX-5 substrate responsible for this effect. Mutants in esx-5 and ppe10 both have impaired capsule integrity as well as reduced surface hydrophobicity. Electron microscopy, immunoblot and flow cytometry analyses demonstrated reduced amounts of surface localized proteins and glycolipids, and morphological differences in the capsular layer. Since capsular proteins secreted by the ESX-1 system are important virulence factors, we tested the effect of the mutations that cause capsular defects on virulence mechanisms. Both esx-5 and ppe10 mutants of Mycobacterium marinum were shown to be impaired in ESX-1-dependent hemolysis. In agreement with this, the ppe10 and esx5 mutants showed reduced recruitment of ubiquitin in early macrophage infection and intermediate attenuation in zebrafish embryos. These results provide a pivotal role for the ESX-5 secretion system and its substrate PPE10, in the capsular integrity of pathogenic mycobacteria. These findings open up new roads for research on the mycobacterial capsule and its role in virulence and immune modulation. PMID- 27280886 TI - Age, Gender and Load-Related Influences on Left Ventricular Geometric Remodeling, Systolic Mid-Wall Function, and NT-ProBNP in Asymptomatic Asian Population. AB - BACKGROUND: Advanced age is associated with left ventricle (LV) remodeling and impaired cardiac function that may increase the risk of heart failure. Even so, studies regarding age-related cardiac remodeling in a large, asymptomatic Asian population remain limited. MATERIALS AND METHODS: We studied 8,410 asymptomatic participants (49.7 +/-11.7 y, 38.9% women) in a health evaluation cohort (2004 2012) at a tertiary center in Northern Taiwan. We analyzed age-related alterations for all echocardiography-derived cardiac structures/functions and the associations with circulating N-terminal prohormone of brain natriuretic peptide (NT-proBNP). We also explored sex-related differences in these measures. RESULTS: In our cohort of 8,410 participants, advanced age was associated with greater LV wall thickness, larger LV total mass (+5.08 g/decade), and greater LV mass index (4.41 g/m2/decade), as well as increased serum NT-proBNP level (+18.89 pg/mL/decade). An accompanying reduction of stress-corrected midwall fractional shortening (-0.1%/decade) with aging was apparent in women after multi-variate adjustment (-0.09%/decade, p = 0.001). Furthermore, women demonstrated greater overall increase in LV wall thickness, LV mass index, and NT-proBNP compared to men (p for interaction: <0.001). All blood pressure components, including systolic, diastolic, and pulse pressures were independently associated with greater wall thickness and LV mass index after adjustment for confounders (all p <0.001). The associations between age and cardiac remodeling or mid-wall functions were further confirmed in a subset of study subjects with repeated follow up by GEE model. CONCLUSIONS: Significant associations of unfavorable LV remodeling and advanced age in our asymptomatic Asian population were observed, along with sex differences. These data may help explain the incidence of some diverse gender-related cardiovascular diseases, especially heart failure. PMID- 27280887 TI - SARTools: A DESeq2- and EdgeR-Based R Pipeline for Comprehensive Differential Analysis of RNA-Seq Data. AB - BACKGROUND: Several R packages exist for the detection of differentially expressed genes from RNA-Seq data. The analysis process includes three main steps, namely normalization, dispersion estimation and test for differential expression. Quality control steps along this process are recommended but not mandatory, and failing to check the characteristics of the dataset may lead to spurious results. In addition, normalization methods and statistical models are not exchangeable across the packages without adequate transformations the users are often not aware of. Thus, dedicated analysis pipelines are needed to include systematic quality control steps and prevent errors from misusing the proposed methods. RESULTS: SARTools is an R pipeline for differential analysis of RNA-Seq count data. It can handle designs involving two or more conditions of a single biological factor with or without a blocking factor (such as a batch effect or a sample pairing). It is based on DESeq2 and edgeR and is composed of an R package and two R script templates (for DESeq2 and edgeR respectively). Tuning a small number of parameters and executing one of the R scripts, users have access to the full results of the analysis, including lists of differentially expressed genes and a HTML report that (i) displays diagnostic plots for quality control and model hypotheses checking and (ii) keeps track of the whole analysis process, parameter values and versions of the R packages used. CONCLUSIONS: SARTools provides systematic quality controls of the dataset as well as diagnostic plots that help to tune the model parameters. It gives access to the main parameters of DESeq2 and edgeR and prevents untrained users from misusing some functionalities of both packages. By keeping track of all the parameters of the analysis process it fits the requirements of reproducible research. PMID- 27280888 TI - On Dipole Moments and Hydrogen Bond Identification in Water Clusters. AB - It is demonstrated that the localized orbitals calculated for a water cluster have small delocalization tails along the hydrogen bonds, that are crucial in determining the resulting dipole moments of the system. (By cutting them, one gets much smaller dipole moments for the individual monomers-close to the values one obtains by using a Bader-type analysis.) This means that the individual water monomers can be delimited only in a quite fuzzy manner, and the electronic charge density in a given point cannot be assigned completely to that or another molecule. Thus, one arrives to the brink of breaking the concept of a water cluster consisting of individual molecules. The analysis of the tails of the localized orbitals can also be used to identify the pairs of water molecules actually forming hydrogen bonds. PMID- 27280889 TI - Efficient Assessment of Developmental, Surgical and Pathological Lymphangiogenesis Using a Lymphatic Reporter Mouse and Its Embryonic Stem Cells. AB - Several lymphatic reporter mouse lines have recently been developed to significantly improve imaging of lymphatic vessels. Nonetheless, the usage of direct visualization of lymphatic vessels has not been fully explored and documented. Here, we characterized a new Prox1-tdTomato transgenic lymphatic reporter mouse line, and demonstrated how this animal tool enables the researchers to efficiently assess developmental, surgical and pathological lymphangiogenesis by direct visualization of lymphatic vessels. Moreover, we have derived embryonic stem cells from this reporter line, and successfully differentiated them into lymphatic vessels in vivo. In conclusion, these experimental tools and techniques will help advance lymphatic research. PMID- 27280890 TI - Trust, but Verify II: A Practical Guide to Chemogenomics Data Curation. AB - There is a growing public concern about the lack of reproducibility of experimental data published in peer-reviewed scientific literature. Herein, we review the most recent alerts regarding experimental data quality and discuss initiatives taken thus far to address this problem, especially in the area of chemical genomics. Going beyond just acknowledging the issue, we propose a chemical and biological data curation workflow that relies on existing cheminformatics approaches to flag, and when appropriate, correct possibly erroneous entries in large chemogenomics data sets. We posit that the adherence to the best practices for data curation is important for both experimental scientists who generate primary data and deposit them in chemical genomics databases and computational researchers who rely on these data for model development. PMID- 27280891 TI - Phonological memory in young children who stutter. AB - This study investigated phonological memory in 5- and 6-year old children who stutter. Participants were 11 children who stutter matched on general language abilities, maternal education level, and sex to 11 typically fluent children. Participants completed norm-referenced nonword repetition and digit span tasks, as well as measures of expressive and receptive vocabulary and articulation. The nonword repetition task included stimuli that ranged from 1 to 7 syllables, while the digit naming task contained number strings containing 2-10 digits. Standardized tests of vocabulary and articulation abilities were tested as well. Groups were comparable on measures expressive vocabulary, receptive vocabulary, and articulation. Despite the fact that the majority of participants scored within typical limits, young children who stutter still performed significantly less well than children who do not stutter on the nonword repetition task. No between-group differences were revealed in the digit naming task. Typically fluent children demonstrated strong correlations between phonological memory tasks and language measures, while children who stutter did not. These findings indicate that young children who stutter may have sub-clinical differences in nonword repetition. PMID- 27280892 TI - Three-Dimensional Analysis of Hemimetameric Segmental Shift in Congenital Scoliosis. AB - STUDY DESIGN: This is a retrospective cohort study. BACKGROUND: Hemimetameric segmental shift (HMMS) is defined as a hemivertebral deformation in which 2 or more hemivertebrae exist on both sides of the spine and are separated by at least 1 normal vertebra. Reports of HMMS are rare and based on simple anterior x-ray images. No reports have used 3-dimensional computed tomography (3D-CT) to analyze both the anterior and posterior elements. The objective of this study was to analyze the morphology and clinical features of HMMS 3 dimensionally. METHODS: HMMS was confirmed in 32 (6.6%, 16 males and 16 females) of 483 patients diagnosed with congenital scoliosis at the study institution between 1998 and 2013. The average age at the first visit was 6 years and 3 months. 3D-CT imaging was performed for 30 patients older than 2 years (average age: 9 y and 8 mo) and used to classify cases according to posterior elements. RESULTS: With regard to the number of hemivertebrae present, 21 patients had 2 hemivertebrae, 7 patients had 3 hemivertebrae, and 2 patients had 4 hemivertebrae. Patients with 2 hemivertebrae predominantly had hemivertebrae in the thoracolumbar spine. Patients were classified into 2 categories: malformation existing at an equal level in anterior and posterior sides (unison HMMS) and malformation existing at nonequal levels (discordant HMMS). Nine patients had unison HMMS and all of them had 2 hemivertebrae (average: 4.6 vertebrae). Twenty-one patients had discordant HMMS, with 12 having 2 hemivertebrae, 7 having 3 hemivertebrae, and 2 having 4 hemivertebrae. CONCLUSIONS: Through 3D-CT analysis, HMMS was categorized as unison or discordant. Discordant HMMS was observed in 21 of 30 (70%) patients and in all patients with >3 hemivertebrae. Diagnosing HMMS, whether unison or discordant, is clinically important and should be done with careful analysis of bone models and/or radiologic images to determine the correct spinal levels. LEVEL OF EVIDENCE: Level IV-diagnostic study. PMID- 27280893 TI - The Recognition, Incidence, and Management of Spinal Cord Monitoring Alerts in Early-onset Scoliosis Surgery. AB - BACKGROUND: The objective of the research was to study the relevance of intraoperative neuromonitoring throughout all stages of surgical management in patients with progressive early-onset scoliosis (EOS).The routine monitoring of spinal cord potentials has gradually become standard of practice among spinal surgeons. However, there is not a consensus that the added expense of this technique necessitates monitoring in all stages of surgical management. METHODS: A retrospective review of 180 surgical cases of 30 patients with EOS from July 2003 to July 2012 was performed. All monitoring alerts as judged by the neuromonitoring team were identified. Both somatosensory-evoked potentials and transcranial electric motor-evoked potentials were studied and no limiting thresholds for reporting electrophysiological changes were deemed appropriate. RESULTS: Of 150 monitored cases there were 18 (12%) monitoring alerts. This represented 40% of the patient cohort over the 9-year study period. CONCLUSIONS: Index versus routine lengthening rate of alerts showed no significant difference in incidence of monitoring alerts. Conversely, several patients whose primary implantation surgeries were uneventful had monitoring alerts later in their treatment course. Intraoperative neuromonitoring is warranted throughout all stages of surgical management of EOS. LEVEL OF EVIDENCE: Level IV. This study is a retrospective review of surgical cases of 30 patients with EOS. PMID- 27280894 TI - Radiation Exposure During Operative Fixation of Pediatric Supracondylar Humerus Fractures: Is Lead Shielding Necessary? AB - BACKGROUND: Factors that impact radiation exposure during operative fixation of pediatric supracondylar humerus (SCH) fractures have been investigated; however, no studies have measured the equivalent dose at the patient's radiosensitive organs. Our hypothesis was that intraoperative fluoroscopy exposes pediatric patients to a significant radiation load and lead shielding of radiosensitive organs is important. The goal of the study was to quantify the patient's radiation exposure during the procedure by measuring the radiation load at the thyroid and gonads. METHODS: A prospective quality improvement project of radiation exposure during percutaneous fixation of isolated SCH fractures was performed over a 4-week period. The c-arm image intensifier was used as the operating table and radiation dosimeters were positioned over the thyroid and gonadal lead shields. Fluoroscopy times were recorded, doses were calculated, and the dosimeters were analyzed. To assure that the prospective cohort was representative of a larger population of SCH fractures, demographics and fluoroscopy time of the prospective cohort were compared with a 12-month retrospective cohort in which dosimetry was not performed. RESULTS: Prospective cohort-18 patients with type 2 (8) and type 3 (10) fractures were prospectively studied with intraoperative measurement of thyroid and gonadal radiation equivalent doses. Mean age was 4.9 years (1.9 to 9.5 y) and mean weight was 21.4 kg (13.1 to 33.5 kg). Mean fluoroscopy time was 65.0 seconds (25.3 to 168.4 s), and absorbed skin dose at the elbow was 0.47 mGy (0.18 to 1.21 mGy). The radiation dosimeters overlying the thyroid and gonads measured minimal radiation indicating equivalent doses of <0.01 mSv for all patients in the prospective cohort.Retrospective cohort-163 patients with type 2 (60) and type 3 (103) fractures were retrospectively studied. The mean age was 5.5 years (0.02 to 13.7 y) and weight was 21.6 kg (2.0 to 71.9 kg). Mean fluoroscopy time was 74.1 seconds (10.2 to 288.9 s), and absorbed skin dose at the elbow was 0.53 mGy (0.07 to 2.07 mGy).There were no statistically significant differences between the cohorts. CONCLUSIONS: The smaller prospective cohort had fluoroscopy times and radiation doses that were not statistically different from the larger retrospective cohort, suggesting that the dosimeter measurements are representative of intraoperative radiation exposure during fixation of pediatric SCH fractures. The equivalent dose to the thyroid and gonads was minimal and approximates daily background radiation. Shielding of radiosensitive organs is appropriate when practical to minimize cumulative lifetime radiation exposure, particularly in smaller patients and when longer fluoroscopy times are anticipated. LEVEL OF EVIDENCE: Level 2. PMID- 27280895 TI - Results of Ponseti Brasil Program: Multicentric Study in 1621 Feet: Preliminary Results. AB - BACKGROUND: The Ponseti method has been shown to be the most effective treatment for congenital clubfoot. The current challenge is to establish sustainable national clubfoot treatment programs that utilize the Ponseti method and integrate it within a nation's governmental health system. The Brazilian Ponseti Program (Programa Ponseti Brasil) has increased awareness of the utility of the Ponseti method and has trained >500 Brazilian orthopaedic surgeons in it. METHODS: A group of 18 of those surgeons had been able to reproduce the Ponseti clubfoot treatment, and compiled their initial results through structured spreadsheet. RESULTS: The study compiled 1040 patients for a total of 1621 feet. The average follow-up time was 2.3 years with an average correction time of approximately 3 months. Patients required an average of 6.40 casts to achieve correction. CONCLUSIONS: This study demonstrates that good initial correction rates are reproducible after training; from 1040 patients only 1.4% required a posteromedial release. LEVEL OF EVIDENCE: Level IV. PMID- 27280897 TI - Deep Surgical Site Infections Following Pediatric Cervical Spine Surgery. AB - OF BACKGROUND DATA: This is the first reported series looking specifically at factors associated with deep surgical site infections (SSI) following pediatric cervical spine surgery. OBJECTIVE: To identify risk factors present in pediatric patients who are at risk for SSI following cervical spine surgery. DESIGN: Level of evidence: level IV-retrospective case series. INTRODUCTION: To date there are no studies regarding SSI in pediatric cervical spine surgery and thus no benchmark data or risk factors have been identified. METHODS: Patients with acute deep SSIs occurring within 90 days of the index operation were identified. Patient and surgical characteristics were analyzed for possible predictors of SSI outcome using penalized likelihood logistic regression analysis. Characteristics analyzed included: age, diagnosis, comorbidity, levels fused, approach, implants used, allograft, halo, body mass index, revision, antibiotic dosing, and occipital plating. RESULTS: A total of 112 patients were included in the study at a mean age of 12.5 years (2 to 18 y). Comorbidities were present in 51 (46%) patients, 15 patients had a documented connective tissue disorder (CTD). The mean number of levels fused was 3.7 (2 to 7) and mean number of screws was 4.4 (2 to 11). Allograft was used alone in 48 patients, occipital plating in 28 patients, and a halo in 39 patients. Deep SSI occurred in 3 patients: two of which had a CTD (1 Trisomy 21, 1 Ehlers-Danlos) and 1 patient with postradiation cervical kyphosis. All were gram-positive infections requiring return to operating room with prolonged IV antibiotics. All patients recovered and fused with spinal implant retention. The incidence of deep SSI was 2.7%. It was determined that a CTD was the only significant predictor of SSI. Subjects with a CTD had 12 times the odds of SSI [odds ratio=12 (1.5, 137.0); P=0.02]. CONCLUSIONS: In our series of pediatric patients the incidence of a deep SSI was 2.7%. The only predictor of SSI was the presence of a CTD. PMID- 27280896 TI - Compliance With a Comprehensive Antibiotic Protocol Improves Infection Incidence in Pediatric Spine Surgery. AB - BACKGROUND: A multidisciplinary task force, designated Target Zero, has developed protocols for prevention of surgical site infection (SSI) for spine surgery at our institution. The purpose of this study was to evaluate how compliance with an antibiotic bundle impacts infection incidences in pediatric spine surgery. METHODS: After institutional review board approval, a consecutive series of 511 patients (517 procedures) who underwent primary spine procedures from 2008 to 2012 were retrospectively reviewed to identify patients who developed SSI. Patients were followed for a minimum of 90 days postoperatively. Compliance data were collected prospectively in 511 consecutive patients and a total of 517 procedures. Three criteria were required for antibiotic bundle compliance: appropriate antibiotics completely administered within 1 hour before incision, antibiotics appropriately redosed intraoperatively for blood loss and time, and antibiotics discontinued within 24 hours postoperatively. A multivariable logistic regression analysis was used to test the association between compliance and the development of an infection. RESULTS: Overall antibiotic bundle compliance rate was 85%. After adjusting for risk category, estimated blood loss, and study year, the likelihood of an infection was increased in the noncompliant group compared with the compliant group (adjusted odds ratio: 3.0, 95% CI, 0.96 9.47, P=0.0587). When expressed as the number needed to treat, strict adherence to antibiotic bundle compliance prevented 1 SSI within 90 days of surgery for every 26 patients treated with the antibiotic bundle. Reasons for noncompliance included failure to infuse preoperative antibiotics 1 hour before incision (10.3%), failure to redose antibiotics intraoperatively based on time or blood loss (5.5%), and failure to discontinue antibiotics within 24 hours postoperatively (1.9%). CONCLUSIONS: Compliance with a comprehensive antibiotic protocol can lead to meaningful reductions in SSI incidences in pediatric spine surgery. Institutions should focus on improving compliance with prophylactic antibiotic protocols to decrease SSI in pediatric spine surgery. LEVEL OF EVIDENCE: Level III-retrospective cohort study. PMID- 27280898 TI - Outcomes of Isolated Varus Derotational Osteotomy in Children With Cerebral Palsy Hip Dysplasia and Predictors of Resubluxation. AB - BACKGROUND: The appropriate intervention for hip subluxation or dislocation in children affected by cerebral palsy (CP) remains controversial. The purpose of this retrospective study was to report radiographic and clinical outcomes following isolated femoral varus derotational osteotomy (VDRO) in children with CP hip dysplasia. Risk factors for resubluxation and avascular necrosis (AVN) were also examined. METHODS: A cohort of 100 patients (199 hips) with CP treated with isolated VDRO between 2003 and 2009 was reviewed. All but 1 patient received bilateral surgery. Patients were followed for an average of 5.4 years (range, 1.03 to 10.20 y). Anteroposterior pelvic radiographs were used to assess migration percentage (MP), Shenton's line, and presence of AVN. Resubluxation was defined as a postoperative break in Shenton's line. Radiographic outcomes and risk analysis was performed in the 91 subjects (179 hips) with radiographic follow-up >1 year. RESULTS: Significant improvement was observed in MP, and all hips had a reconstituted Shenton's line following surgery. Over the course of follow-up, 16% of hips were noted to have a repeat break in Shenton's line. Univariate risk analysis showed preoperative MP, Gross Motor Function Classification System (GMFCS) level, and age at surgery were risk factors for a recurrent line break. Preoperative MP and GMFCS level were found to be predictors of resubluxation in multivariate analysis. AVN was detected in 10 hips (5.7%). GMFCS level V patients were more at risk for resubluxation, but less at risk for AVN when compared with ambulatory (GMFCS I/II/II) patients and GMFCS level IV patients. CONCLUSIONS: Performing a VDRO without additional procedures provided a stable and concentrically reduced hip joint in this population of children with CP. Attention should be paid to initial ambulatory status during the postoperative period. Concomitant procedures such as pelvic osteotomy should be considered for patients of GMFCS level IV and V, as these patients were more at risk for recurrent subluxation. LEVEL OF EVIDENCE: Level III-retrospective comparative study. PMID- 27280899 TI - Ulna Growth Patterns After Soft Tissue Release With Bilobed Flap in Radial Longitudinal Deficiency. AB - BACKGROUND: Centralization is commonly utilized for treating the severely deviated wrist in radial longitudinal deficiency (RLD). Individuals with RLD have congenital shortening of the ulna and previous studies have shown that traditional centralization, in particular with notching of the carpus, results in additional ulnar growth retardation. At our institution, we use a technique of soft tissue release with bilobed flap. We examined if this technique preserves the growth potential of the distal ulna, therefore, avoiding an additionally shortened forearm. METHODS: We retrospectively reviewed serial radiographs of 16 patients with 18 wrists who had at least 3 years of follow-up after a soft tissue release with bilobed flap. Radiographic lengths were measured using the method described by Heikel. Percentage of normal growth was calculated using normative data published by Maresh. Comparisons were made with preoperative, postoperative, and final follow-up studies. RESULTS: The average length of follow-up was 9.2 years (range, 3 to 16.3 y) with an average age of 11.6 years (range, 5.2 to 17.5 y). The average age at the time of surgery was 27 months (range, 14 to 48 mo). A minimum of 3 radiographic studies were available for each subject. The average ulna length preoperatively was 63.9% of age-matched normal length (51.4% to 75.3%). The average ulna length at final follow-up was 61.9% of age-matched normal length (48.5% to 70.3%). The difference was not statistically significant. In addition, there were no distal ulnar physeal arrests. CONCLUSIONS: Soft tissue release with bilobed flap does not affect ulna growth like traditional centralization procedures can. This procedure has previously been shown to retain motion and have similar recurrence rates to formal centralizations. Therefore, we advocate that it be considered more widely for use in patients with RLD and significant wrist deviation to maximize growth and improve hand position. Soft tissue release with bilobed flap can be safely used on young children and preserve ulnar growth. LEVEL OF EVIDENCE: Level IV-therapeutic. PMID- 27280900 TI - Botulinum Toxin Injection for Internal Rotation Contractures in Brachial Plexus Birth Palsy. A Minimum 5-Year Prospective Observational Study. AB - BACKGROUND: Brachial plexus birth palsy is frequently associated with internal rotation contractures of the shoulder as a result of muscle imbalance. The purpose of this study is to assess the effect of botulinum toxin A (BTX-A) injection in the subscapular (SC) muscle on external rotation and the need for tendon transfer for external rotation of the shoulder. METHODS: A prospective comparative study was performed including 15 consecutive patients treated with BTX-A and a historic control group of 67 patients with mean age 30 months (SD 10). The BTX-A injection (2 IU/kg body weight) was performed immediately following MRI under general anesthesia in the SC muscle. Passive external rotation, the need for tendon transfer surgery, glenohumeral deformity, and muscle degeneration were evaluated. The hazard ratio for no relapse of internal rotation contracture after BTX-A injection compared with no BTX-A injection was calculated. RESULTS: In the BTX-A group, the passive external rotation in adduction increased from -1 degree (95% CI, -10 to 8) to 32 degrees (95% CI, 17 46) at 3 months and 6 patients were indicated for surgery compared with a decline from -2 degrees (95% CI, -7 to 3) to -11 degrees (95% CI, -17 to -6) in the control group with 66 indications for surgery. At 5 years of follow-up, 10 patients in the BTX-A group were indicated for surgery with a hazard ratio of 4.0 (95% CI, 1.9 to 8.4). CONCLUSIONS: BTX-A injection in the SC muscle of brachial plexus birth palsy patients can reduce internal rotation contractures and subsequently the need for tendon transfer surgery. At 5 years of follow-up a relapse was seen in 67% of the patients treated with BTX-A. Because at MRI less SC degeneration was found in the good responders on BTX-A treatment, this group seems to be the best target group. Further research is needed on patient selection for BTX-A injection including glenohumeral deformity, SC degeneration, as well as doses of BTX-A to be used. LEVEL OF EVIDENCE: Level II-prospective comparative study. PMID- 27280901 TI - Blood Transfusion Incidence, Risk Factors, and Associated Complications in Surgical Treatment of Hip Dysplasia. AB - BACKGROUND: Perioperative bleeding requiring blood transfusion is a known complication of hip dysplasia (HD) surgery. Here we examine rates of, risk factors for, and postoperative complications associated with transfusion during HD surgery. METHODS: The National Surgical Quality Improvement Program (NSQIP) Pediatric database was queried for patients treated by an orthopaedist from 2012 to 2013. HD cases were categorized by Current Procedural Terminology codes into femoral osteotomies, acetabular osteotomies, combined femoral/acetabular osteotomies, and open reductions. Patients were grouped by comorbidities: neuromuscular (NM) disease (eg, cerebral palsy) group, non-NM with other comorbidity (Other) group, and no known comorbidity (NL) group. Patients were stratified by weight-normalized transfusion volume. Multivariate regression analysis of transfusion association with procedures, demographics, comorbidities, preoperative laboratory values, and 30-day complications was performed. RESULTS: A total of 1184 HD cases were included. Transfusion rates for the NL, Other, and NM groups, respectively, were 44/451 (9.8%), 61/216 (28.2%), and 161/517 (31.1%). Transfusion volumes (mean+/-SD) for the NL, Other, and NM groups, respectively, were 8.4+/-5.4, 13.9+/-8.8, and 15.5+/-10.0 mL/kg (P<0.001). Combined osteotomies had the highest transfusion rates in the NM and Other groups (35.7% and 45.8%, respectively), whereas acetabular osteotomies had the highest rate in the NL group (15.8%). Open reductions had the lowest transfusion rate (all groups). Longer operations were independently associated with transfusion (all groups, per hour increase, OR>1.5, P<0.001). Independent patient risk factors included preoperative hematocrit <31% (NM group, OR=18.42, P=0.013), female sex (NL group, OR=3.55, P=0.008), developmental delay (NM group, OR=2.37, P=0.004), pulmonary comorbidity (NM group, OR=1.73, P=0.032), and older age (NL group, per year increase: OR=1.29, P<0.001). In all groups, transfusion was associated with longer hospitalization (P<0.001). We observed a volume-dependent increase in overall complication rate within the Other group for transfusion volumes >15 mL/kg (25.0% vs. 5.4% for <15 mL/kg, P=0.048). CONCLUSIONS: We identified several risk factors for transfusion in HD surgery. The incidence of transfusion in HD surgery and its association with adverse outcomes warrants development of appropriate patient management guidelines. LEVEL OF EVIDENCE: Level III prognostic. PMID- 27280902 TI - Primary Liver Carcinosarcoma and 18F-FDG PET/CT. AB - Primary liver carcinosarcoma is a very rare, malignant neoplasm that is concomitantly composed of a mixture of sarcomatous and carcinomatous elements. In the present study, an initial staging FDG PET/CT showed intense FDG uptake in a patient with liver carcinosarcoma composed of hepatocellular carcinoma and rhabdomyosarcoma. Two months after surgical resection, a restaging PET/CT showed rapid progression of the disease with abdominal and lung metastases, indicating aggressive feature of the disease. The case shows the importance to repeat a restaging PET/CT at early time after surgery for a patient with liver carcinosarcoma to monitor disease progression. PMID- 27280903 TI - Quality and Safety in Health Care, Part XIV: The External Environment and Research for Diagnostic Processes. AB - The work system in which diagnosis takes place is affected by the external environment, which includes requirements such as certification, accreditation, and regulations. How errors are reported, malpractice, and the system for payment are some other aspects of the external environment. Improving the external environment is expected to decrease errors in diagnosis. More research on improving the diagnostic process is needed. PMID- 27280904 TI - Early Assessment of Treatment Response in Takayasu Arteritis: An 18FDG PET Procedure. AB - PURPOSE: To describe a procedure allowing early assessment of treatment response in Takayasu arteritis (TA) patients by averaging the standard uptake value obtained from N hottest voxels irrespective of their location within the F-FDG positive vessel walls (SUVmax-N). METHODS: The procedure is illustrated in a score-V TA patient before and after 1 and 3 months of glucocorticoid treatment (scans 0-1-3, respectively). Comparison between scans was made by using SUVmax-N repeatability percentages with 95-99-99.9% reliability. RESULTS: No significant difference in SUVmax (ie, N = 1) was found between scan 0 and 1, and between scan 1 and 3, with 95% reliability. A significant difference in SUVmax-N was found with 99.9% reliability for each scan pair by averaging N = 4100-515 hottest voxels (total hottest volume of 100.0-12.6 mL), respectively. CONCLUSIONS: The proposed SUVmax-N procedure may be an efficient tool to early assess treatment response in TA patients. Further studies involving series of patients with large vessel vasculitis are warranted to investigate its usefulness in their management. PMID- 27280905 TI - A Solitary Metastasis for a Malignant Schwannoma in the Gallbladder Detected by 18F-FDG PET/CT. AB - A 63-year-old woman with a history of malignant schwannoma in the left shoulder (pT1aNxMx) was treated with surgical resection in 2012. During follow-up, patient developed a metastasis in the right lung treated by further surgical intervention. For a suspicion on persistent disease in the lung, patient was sent to FDG PET/CT examination, which showed a focal uptake in the gallbladder. The patient underwent cholecystectomy, and a solitary metastasis from schwannoma was diagnosed by pathology. This case highlights that, in patients with a malignant schwannoma, a careful differential diagnosis should be made in case of a significant FDG uptake in the gallbladder. PMID- 27280906 TI - Coincidental Observation of Global Hypometabolism in the Brain on PET/CT of an AIDS Patient With High-Grade Pulmonary Non-Hodgkin Lymphoma. AB - AIDS-related dementia complex is the most severe form of cognitive dysfunction in a patient infected with human immunodeficiency virus. The use of FDG PET/CT to diagnose AIDS-related dementia complex has been studied previously and shows various specific metabolic patterns from striatal hypermetabolism in early asymptomatic stage to global hypometabolism in advanced stages. We present a case of a 49-year-old patient with long-standing human immunodeficiency virus infection, where global brain hypometabolism was noted coincidentally on FDG PET/CT done for initial staging of primary pulmonary non-Hodgkin lymphoma. PMID- 27280907 TI - Sarcoid Pericarditis and Large Vessel Vasculitis Detected on FDG PET/CT. AB - A 65-year-old woman with history of sarcoidosis, hypertension, and peripheral vascular disease presented with lower extremity claudication and low left ventricular ejection fraction of 45% on echocardiogram. Further FDG PET/CT revealed hypermetabolic bilateral chest lymphadenopathy and pulmonary nodules in a butterfly-shaped distribution pattern, which was typically seen in patients with sarcoidosis. In addition, abnormal increased radiotracer uptake was present in pericardium, and along the walls of inferior vena cava, aorta, and pulmonary artery, which correlated with delayed enhancement on further cardiac MRI. These findings were suggestive of sarcoid-related pericarditis and great vessel vasculitis. PMID- 27280908 TI - Increased Background Activity in DMSA Scintigraphy of a Nonazotemic Patient With beta-Thalassemia Major. AB - Renal DMSA uptake provides an index for evaluation of the functional tubular mass, which depends on the renal blood flow, proximal tubular cell membrane function, and urinary acid-base balance. We present a case of a nonazotemic 48 year-old adult with beta-thalassemia major under regular blood transfusions and iron chelation therapy that underwent DMSA scan showing minor cortical abnormalities and high background activity, featuring prominent cardiac blood pool and liver uptake. This case highlights the pitfall of high background activity during DMSA study in patients with beta-thalassemia major due to tubular disorders. PMID- 27280930 TI - Testing relationships between DSM-5 Section III maladaptive traits and measures of self and interpersonal impairment in Italian community dwelling adults. AB - In order to study the relationships between DSM-5 Section III maladaptive personality traits and personality dysfunction, 312 Italian community dwelling adults completed the Italian translations of the Personality Inventory for DSM-5 (PID-5) and the Measure of Disordered Personality Functioning Scale (MDPF); participants were also administered the Iowa Personality Disorder Screen (IPDS). Consistent with previous findings, 22 (88.0%) PID-5 maladaptive trait scales showed moderate and significant correlations with MDPF Non Coping (median r value = .32), and Non Cooperativeness, (median r value = .24) scales. Regression analyses showed that PID-5 trait scales explained roughly 59% and 35% of the variance in MDPF Non Coping and Non Cooperativeness scales, respectively. PID-5 traits were significantly associated also with the IPDS total score, adjusted R2 = .45, p < .001. As a whole, our data seemed to indicate that the wide majority of the PID-5 scales showed significant relationships of at least moderate size with a self-report measure of personality dysfunction, lending further support to the criterion validity of the PID-5. (PsycINFO Database Record PMID- 27280931 TI - Biological Activity of Polynesian Calophyllum inophyllum Oil Extract on Human Skin Cells. AB - Oil from the nuts of Calophyllum inophyllum, locally called "Tamanu oil" in French Polynesia, was traditionally used for wound healing and to cure various skin problems and ailments. The skin-active effect of "Tamanu oil emulsion" was investigated on human skin cells (keratinocytes and dermal fibroblasts) and showed cell proliferation, glycosaminoglycan and collagen production, and wound healing activity. Transcriptomic analysis of the treated cells revealed gene expression modulation including genes involved in the metabolic process implied in O-glycan biosynthesis, cell adhesion, and cell proliferation. The presence of neoflavonoids as bioactive constituents in Tamanu oil emulsion may contribute to these biological activities. Altogether, consistent data related to targeted histological and cellular functions brought new highlights on the mechanisms involved in these biological processes induced by Tamanu oil effects in skin cells. PMID- 27280932 TI - Labdane Diterpenoids from Salvia leriifolia: Absolute Configuration, Antimicrobial and Cytotoxic Activities. AB - Fractionation of an n-hexane extract of the aerial parts of Salvia leriifolia led to the isolation of two new (1, 2) and two known (3, 4) labdane diterpenoids, together with three other known compounds. The structures were established by a combination of 1D and 2D NMR, and HRESIMS. The structures of 1 and 3 were confirmed by single-crystal X-ray analysis. The absolute configuration of 1-4 was established by electronic circular dichroism spectroscopy. Compounds 1-4 were evaluated for their cytotoxic activities against MCF-7 human breast cancer cells. Labdanes 3 and 4 were additionally tested against MDA-MB231 human breast cancer and DU-145 human prostate cancer cell lines. Compound 4 showed IC50 values of 25, 50, and 50 uM against MCF-7, MDA-MB231, and DU-145 cells, respectively. Compounds 1-4 were tested for activity against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacteria. Compound 3 showed an MIC of 213 uM against methicillin-resistant S. aureus. PMID- 27280933 TI - A Simple and Rapid HPLC-PDA MS Method for the Profiling of Citrus Peels and Traditional Italian Liquors. AB - A chromatographic method for the qualitative and quantitative characterization of peels and preparations based on different species of Citrus was developed in order to obtain a complete profile of the constituents, including flavonoids and protoalkaloids. Commercial peels of sweet orange, lemon, mandarin, and grapefruit were analyzed. Seventeen constituents including flavanones, flavones, polymethoxyflavones, and protoalkaloids were identified by HPLC-PDA, HPLC-MS, and HPLC-MS/MS using a comparison of retention times and UV-Vis and MS spectra with reference standards and literature data. The total amount of flavanones [neoeriocitrin (5), naringin (8) and hesperidin (9)] and polymethoxflavones [sinensetin (12), nobiletin (14), 3,5,6,7,8,3',4'-heptamethoxyflavone (15), and tangeretin (16)] was determined and expressed as naringin (8) or hesperidin (9), and sinensetin (12), respectively. The protoalkaloid synephrine was detected in all samples, except in grapefruit, but its content was lower than the limit of quantification. Qualitative and quantitative chemical profiles of three different Italian aromatic liquors ("Limoncello", "Arancello", and "Mandarinetto"), prepared according to traditional recipes, were also analyzed. PMID- 27280934 TI - A Novel Self-Microemulsifying System for the Simultaneous Delivery and Enhanced Oral Absorption of Curcumin and Resveratrol. AB - The use of curcumin and resveratrol in combination has now become increasingly of interest because of their synergistic effects as therapeutic agents for various diseases, especially cancer. To overcome the poor oral bioavailability of both compounds and improve patient compliance, a novel self-microemulsifying formulation containing curcumin together with resveratrol was developed. Capryol 90, Cremophor EL, and Labrasol were selected as the oil, surfactant, and co surfactant in the formulation, respectively, based on the solubility study of both compounds. More than 70 % and 80 % of curcumin and resveratrol, respectively, were released in 20 min. The formulation formed a fine oil in water microemulsion with droplet sizes in aqueous media of 15-20 nm. In addition, the formulation containing curcumin and resveratrol showed greater antioxidant activity than that of the formulations with individual compounds, while the cytotoxic activity against HT-29 of the co-formulation (IC50 = 18.25 uM; curcumin and resveratrol in the ratio 1 : 1) was less than the formulation with only curcumin (IC50 = 30.1 uM) and only resveratrol (IC50 = 25.4 uM). After oral administration to rabbits, the self-microemulsifying formulation containing curcumin together with resveratrol increased the total plasma concentrations of curcumin and resveratrol by 10-fold and 6-fold, respectively, compared to the unformulated combination. This study clearly demonstrated the potential use of the self-microemulsifying formulation for co-delivery, and enhanced oral absorption of poorly water-soluble natural compounds. In addition, the combination was found to produce synergistic antioxidant activity and cytotoxicity against HT-29 cells. PMID- 27280935 TI - Effects of a Hot-Water Extract of Allium hookeri Roots on Bone Formation in Human Osteoblast-Like MG-63 Cells In Vitro and in Rats In Vivo. AB - Allium hookeri is a wild herb found mainly in the Himalayas, growing at altitudes of 1400-4200 m. A. hookeri is widely consumed as a vegetable and herbal medicine in Asia, but its effects on bone health have not been reported previously. This study investigated the effects of a hot-water extract of A. hookeri roots on bone formation. The hot-water extract significantly increased the proliferation of in vitro human osteoblast-like MG-63 cells and the stimulatory effects on osteoblast differentiation were noticeably greater for the hot-water extract than for daidzein (a positive control), as reflected by alkaline phosphatase activity, collagen content, and mineral deposition. Expression of the bone-remodeling marker osteocalcin production and bone microstructural parameters were significantly improved in Sprague-Dawley rats in vivo after oral treatment with the hot-water extract compared with their control (saline-administered) counterparts. The chemical compounds of the hot-water extract were characterized by liquid chromatography-mass spectrometry, and alliin, sinapic acid, and ferulic acid, which exert beneficial effects on bone health, were identified. These findings indicate that A. hookeri can be used as a natural resource for increasing bone formation. This is the first report of the anabolic effects of A. hookeri extracts on bone formation in vitro and in vivo. PMID- 27280936 TI - Isolation of Bioactive Rotenoids and Isoflavonoids from the Fruits of Millettia caerulea. AB - Three new rotenoids (1-3), two new isoflavonoids (4 and 5), and six known analogues (6-11) were isolated from an n-hexane partition of a methanol extract of the fruits of Millettia caerulea, with the structures of the new compounds elucidated by analysis of their spectroscopic data. The relative configurations of the rotenoids were determined by interpretation of their NMR spectroscopic data, and their absolute configurations were established using electronic circular dichroism spectra and specific rotation values. All compounds isolated were evaluated for their cell growth inhibitory activity against the HT-29 human colon cancer cell line, and the known compounds, (-)-3-hydroxyrotenone (6) and ( )-rotenone (7), were found to be potently active. When tested in an NF-kappaB inhibition assay, compound 6 showed activity. This compound, along with the new compound, (-)-caeruleanone D (1), and the known compound, ichthynone (8), exhibited K-Ras inhibitory potency. Further bioactivity studies showed that the new compounds, (-)-3-deoxycaeruleanone D (2) and (-)-3-hydroxycaeruleanone A (3), and the known compounds 8 and 11 induced quinone reductase in murine Hepa 1c1c7 cells. PMID- 27280937 TI - Astagalus Polysaccharide Attenuates Murine Colitis through Inhibiton of the NLRP3 Inflammasome. AB - Astragalus polysaccharide is an important bioactive component of Astragalus membranaceus, an herb used in traditional Chinese medicine for treating inflammatory bowel disease. The NOD-like receptor protein 3 inflammasome plays an important role in the pathogenesis of inflammatory bowel disease. However, little is known about the role of NOD-like receptor protein 3 inflammasome in Astragalus polysaccharide-treated mice with experimental colitis. For this study, we investigated the molecular mechanisms that underlie the treatment of inflammatory bowel disease by Astragalus polysaccharide. We show that Astragalus polysaccharide treatment reduces the disease activity index and histological injury scores compared to the colitis model group. Astragalus polysaccharide also effectively inhibited the expression of NOD-like receptor protein 3, apoptotic speck protein containing a c-terminal caspase recruitment domain, caspase-1, interleukin-18, and interleukin-1beta, as shown by quantificational RT-PCR or the enzyme-linked immunosorbent assay. Furthermore, Astragalus polysaccharide treatments produced significant dose-dependent improvements in dextran sulfate sodium-induced experimental colitis. Our data provide the reliable evidence that Astragalus polysaccharide is able to exert a therapeutic effect in dextran sulfate sodium-induced colitis by inhibiting the activation of the NOD-like receptor protein 3 inflammasome, which acts to decrease the production of inflammatory factors such as interleukin-18 and interleukin-1beta. PMID- 27280939 TI - Sex differences in mortality following isolated traumatic brain injury among older adults. AB - BACKGROUND: Older adults have the highest rates of hospitalization and mortality from traumatic brain injury (TBI), yet outcomes in this population are not well studied. In particular, contradictory reports on the protective effect of female sex on mortality following TBI may have been related to age differences in TBI and other injury severity and mechanism. The objective of this study was to determine if there are sex differences in mortality following isolated TBI among older adults and compare with findings using all TBI. A secondary objective was to characterize TBI severity and mechanism by sex in this population. METHODS: This was a retrospective cohort study conducted among adults aged 65 and older treated for TBI at a single large Level I trauma center from 1996 to 2012 (n = 4,854). Individuals treated for TBI were identified using International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Isolated TBI was defined as an Abbreviated Injury Scale score of 0 for other body regions. Our primary outcome was mortality at discharge. RESULTS: Among those with isolated TBI (n = 1,320), women (45% of sample) were older (mean [SD], 78.9 [7.7] years) than men (76.8 [7.5] years) (p < 0.001). Women were more likely to have been injured in a fall (91% vs. 84%; p < 0.001). Adjusting for multiple injury severity measures, female sex was not significantly associated with decreased odds of mortality following isolated TBI (odds ratio, 1.01; 95% confidence interval, 0.66-1.54). Using all TBI cases, adjusted analysis found that female sex was significantly associated with decreased odd of mortality (odds ratio, 0.73; 95% confidence interval, 0.59-0.89). CONCLUSION: We found no sex differences in mortality following isolated TBI among older adults, in contrast with other studies and our own analyses using all TBI cases. Researchers should consider isolated TBI in outcome studies to prevent residual confounding by severity of other injuries. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level IV. PMID- 27280940 TI - Low-volume resuscitation using polyethylene glycol-20k in a preclinical porcine model of hemorrhagic shock. AB - INTRODUCTION: Polyethylene glycol-20k (PEG-20k) is highly effective for low volume resuscitation (LVR) by increasing tolerance to the low-volume state. In our rodent shock model, PEG-20k increased survival and expanded the "golden hour" 16-fold compared to saline. The molecular mechanism is largely attributed to normalizations in cell and tissue fluid shifts after low-flow ischemia resulting in efficient microvascular exchange. The objective of this study was to evaluate PEG-20k as an LVR solution for hemorrhagic shock in a preclinical model. METHODS: Anesthetized male Yorkshire pigs (30-40 kg) were hemorrhaged to a mean arterial pressure (MAP) of 35 to 40 mm Hg. Once lactate reached 7 mmol/L, either saline (n = 5) or 10% PEG-20k (n = 5) was rapidly infused at 10% calculated blood volume. The primary outcome was LVR time, defined by the time from LVR administration to the time when lactate again reached 7 mmol/L. Other outcomes measured included MAP, heart rate, cardiac output, mixed venous oxygen saturation, splanchnic blood flow, and hemoglobin. RESULTS: Relative to saline, PEG-20k given after controlled hemorrhage increased LVR time by 16-fold, a conservative estimate given that the lactate never rose after LVR in the PEG-20k group. Survival was 80% for PEG-20k LVR compared to 0% for the saline controls (p < 0.05). Polyethylene glycol-20k also significantly decreased heart rate after hemorrhage and increased cardiac output, MAP, splanchnic flow, and mixed venous oxygen saturation. Falling hemoglobin concentrations suggested sizable hemodilution from fluid shifts into the intravascular compartment. CONCLUSIONS: In a preclinical model of controlled hemorrhagic shock, PEG-20k-based LVR solution increased tolerance to the shock state 16-fold compared to saline. Polyethylene glycol-20k is a superior crystalloid for LVR that may increase safe transport times in the prehospital setting and find use in hospital emergency departments and operating rooms for patients awaiting volume replacement or normalization of cell, tissue, and compartment fluid volumes. PMID- 27280941 TI - Availability of on-site acute vascular interventional radiology techniques performed by trained acute care specialists: A single-emergency center experience. AB - INTRODUCTION: Comprehensive treatment of a patient in acute medicine and surgery requires the use of both surgical techniques and other treatment methods. Recently, acute vascular interventional radiology techniques (AVIRTs) have become increasingly popular, enabling adequately trained in-house experts to improve the quality of on-site care. METHODS: After obtaining approval from our institutional ethics committee, we conducted a retrospective study of AVIRT procedures performed by acute care specialists trained in acute medicine and surgery over a 1-year period, including those conducted out of hours. Trained acute care specialists were required to be certified by the Japanese Association of Acute Medicine and to have completed at least 1 year of training as a member of the endovascular team in the radiology department of another university hospital. The study was designed to ensure that at least one of the physicians was available to perform AVIRT within 1 h of a request at any time. Femoral sheath insertion was usually performed by the resident physicians under the guidance of trained acute care specialists. RESULTS: The study sample comprised 77 endovascular procedures for therapeutic AVIRT (trauma, n = 29, and nontrauma, n = 48) among 62 patients (mean age, 64 years; range, 9-88 years), of which 55% were male. Of the procedures, 47% were performed out of hours (trauma, 52%; and nontrauma, 44%). Three patients underwent resuscitative endovascular balloon occlusion of the aorta in the emergency room. No major device-related complications were encountered, and the overall mortality rate within 60 days was 8%. The recorded causes of death included exsanguination (n = 2), pneumonia (n = 2), sepsis (n = 1), and brain death (n = 1). CONCLUSION: When performed by trained acute care specialists, AVIRT seems to be advantageous for acute on-site care and provides good technical success. Therefore, a standard training program should be established for acute care specialists or trauma surgeons to make these techniques a part of the standard regimen. LEVEL OF EVIDENCE: Therapy/care management study, level V. PMID- 27280942 TI - Does sex matter? Effects on venous thromboembolism risk in screened trauma patients. AB - BACKGROUND: Sex is associated with disparate risk of venous thromboembolism (VTE) in nontrauma patients, with increased risk seen during pregnancy and in women on hormone-containing medications. Sex effects on VTE after trauma are unclear. Some studies have demonstrated no effect whereas others have instead shown a higher incidence of VTE among men. We hypothesized that male sex would increase the risk of VTE across all age groups in trauma patients undergoing standardized duplex screening. METHODS: All admissions to a Level I academic trauma center 2000 to 2014 were reviewed. We excluded patients for age <18 years, pregnancy, pre admission anticoagulant use, and hospital length of stay (LOS) <72 hours. A strict venous duplex screening protocol was followed. Female patients were subcategorized into pre- and post-menopausal groups based on age (18-44 vs. >= 55 years). Bivariate analysis and logistic regression were used to identify variables correlating with VTE risk. RESULTS: A total of 8,726 patients met inclusion criteria. The overall VTE rate was 5.3%. Bivariate analysis did not find a difference in VTE risk by sex (5.1% women vs. 5.4% men, p = 0.565), or between women and men within age-defined menopausal categories (pre-menopausal women 3.9% vs. men 4.7%, p = 0.293; post-menopausal women 5.9% vs. men 7.0%, p = 0.22). Logistic regression (see figure) did identify other risk factors for VTE including age >=55 (adjusted odds ratio [AOR] 2.0), increasing ISS (AOR 1.5-2.1), penetrating mechanism of injury (AOR 2.2), lower extremity injury (AOR 1.7), need for mechanical ventilation (AOR 2.1), and increasing hospital length of stay (LOS 7-28 days, AOR 3.8; LOS > 28 days, AOR 9.1). CONCLUSION: There was no difference in VTE rates based on patient sex, even after controlling for menopausal status. Aggressive VTE screening of over 8,700 patients did identify several other patient populations at increased risk of developing VTE. More intensive VTE prophylaxis may be appropriate in these patients. LEVEL OF EVIDENCE: Epidemiologic study, level III; therapeutic study, level V. PMID- 27280943 TI - Do lactate levels in the emergency department predict outcome in adult trauma patients? A systematic review. AB - BACKGROUND: Serum lactate may be associated with clinical outcomes in trauma, even in the absence of physiological abnormality. Sensitive markers of injury and outcomes are needed to guide triage and management of trauma patients within the Emergency Department. We completed a systematic review to determine if lactate levels in adult trauma patients presenting to the Emergency Department were associated with clinical outcomes including mortality. METHODS: A systematic literature search was conducted in August 2014, updated in March 2016, using MEDLINE, Embase, and CINAHL. Abstracts and full texts were screened for inclusion by two independent reviewers using predetermined inclusion and exclusion criteria. Data extraction and quality assessment was performed by each reviewer using a standardized form. A total of 998 studies were screened; 28 studies were included and reviewed. RESULTS: The 28 studies recruited 44,154 adults in eight countries between 1997 and 2016. Twenty-one studies found a significant association between elevated Emergency Department lactate and risk of mortality. Three studies looked at lactate clearance; two showed poor clearance was an additional determinant of mortality, but the other found no association. Ten studies also found an association between elevated lactate and other clinical outcomes. These included injury severity, Intensive Care Unit admission, length of hospital stay, organ failure, respiratory complications, blood loss, blood product requirement, catecholamine support, or emergency operation. Two studies concluded that lactate levels do not affect management. CONCLUSIONS: This review shows that elevated Emergency Department lactate levels are associated with mortality and may be associated with other clinical outcomes in adult trauma patients. We conclude that lactate is a useful marker of outcome in trauma, in addition to current markers of severity. The potential roles of serial lactate measurement and lactate clearance require further research. LEVEL OF EVIDENCE: Systematic review, level III. PMID- 27280944 TI - Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis. AB - OBJECTIVE: DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP). DESIGN: DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay. RESULTS: The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p<0.001), which was significantly negatively correlated with the probing depth (p=0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p=0.03). CONCLUSION: The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients. PMID- 27280945 TI - Fluoride induced endoplasmic reticulum stress and calcium overload in ameloblasts. AB - OBJECTIVE: The aim of the study was to evaluate the involvement of endoplasmic reticulum stress and intracellular calcium overload on the development of dental fluorosis. METHODS: We cultured and exposed rat ameloblast HAT-7 cells to various concentrations of fluoride and measured apoptosis with flow cytometry and intracellular Ca2+ changes using confocal microscopy, investigated the protein levels of GRP78, calreticulin, XBP1 and CHOP by western blotting, and their transcriptional levels with RT-PCR. We also created an in vivo model of dental fluorosis by exposing animals to various concentrations of fluoride. Subsequently, thin dental tissue slices were analyzed with H&E staining, immunohistochemical staining, and transmission electron microscopy, TUNEL assay was also performed on dental tissue slices for assessment of apoptosis. RESULT: High fluoride concentration was associated with decreased ameloblast proliferation, elevated ameloblast apoptosis, and increased intracellular Ca2+ in vitro. The translation and transcription of the proteins associated with endoplasmic reticulum stress were significantly elevated with high concentrations of fluoride. Based on immunohistochemical staining, these proteins were also highly expressed in animals exposed to high fluoride concentrations. Histologically, we found significant fluorosis-like changes in tissues from animals exposed to high fluoride concentrations. Transmission electron microscopy cytology indicated significant apoptotic changes in tissues exposed to high concentrations of fluoride. CONCLUSIONS: These results indicate that exposure to high levels of fluoride led to endoplasmic reticulum stress which induced apoptosis in cultured ameloblasts and in vivo rat model, suggesting an important role of calcium overload and endoplasmic reticulum stress triggered by high concentrations of fluoride in the development of dental fluorosis. PMID- 27280946 TI - Interactions of a Tetrazine Derivative with Biomembrane Constituents: A Langmuir Monolayer Study. AB - Tetrazine (Tz) is expected to be used for bioimaging and as an analytical reagent. It is known to react very fast with trans-cyclooctene under water in organic chemistry. Here, to understand the interaction between Tz and biomembrane constituents, we first investigated the interfacial behavior of a newly synthesized Tz derivative comprising a C18-saturated hydrocarbon chain (rTz-C18) using a Langmuir monolayer spread at the air-water interface. Surface pressure (pi)-molecular area (A) and surface potential (DeltaV)-A isotherms were measured for monolayers of rTz-C18 and biomembrane constituents such as dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG), dipalmitoyl phosphatidylethanolamine (DPPE), palmitoyl sphingomyelin (PSM), and cholesterol (Ch). The lateral interaction between rTz-C18 and the lipids was thermodynamically elucidated from the excess Gibbs free energy of mixing and two dimensional phase diagram. The binary monolayers except for the Ch system indicated high miscibility or affinity. In particular, rTz-C18 was found to interact more strongly with DPPE, which is a major constituent of the inner surface of cell membranes. The phase behavior and morphology upon monolayer compression were investigated by using Brewster angle microscopy (BAM), fluorescence microscopy (FM), and atomic force microscopy (AFM). The BAM and FM images of the DPPC/rTz-C18, DPPG/rTz-C18, and PSM/rTz-C18 systems exhibited a coexistence state of two different liquid-condensed domains derived mainly from monolayers of phospholipids and phospholipids-rTz-C18. From these morphological observations, it is worthy to note that rTz-C18 is possible to interact with a limited amount of the lipids except for DPPE. PMID- 27280947 TI - Rh(III)-Catalyzed C-C/C-N Coupling of Imidates with alpha-Diazo Imidamide: Synthesis of Isoquinoline-Fused Indoles. AB - Imidate esters and diazo compounds have been established as bifunctional substrates for the construction of biologically active fused heterocycles via rhodium-catalyzed C-H activation and C-C/C-N coupling. This reaction occurs under mild conditions with high efficiency, step economy, and low catalyst loading. PMID- 27280953 TI - Immunomodulatory effects of polysaccharide compounds in macrophages revealed by high resolution AFM. AB - Polysaccharide compounds (PCs), which composed of different kinds of polysaccharides always isolated from different kinds of traditional Chinese medicine, are now attracting more and more attentions due to their strong immunomodulatory activities beyond the corresponding one-component polysaccharides. In this study, we demonstrated for the first time that PCs-1 and PCs-2 had strong immunomodulatory effects on macrophages both in in vitro and in vivo models by atomic force microscopy (AFM). By high resolution AFM imaging, PCs 1 and PCs-2 were found to inhibit LPS induced cell surface particle size and roughness increase in RAW264.7 macrophages, demonstrating the anti-inflammatory effects of PCs-1 and PCs-2 on macrophages. PCs-1 and PCs-2 were also proved to increase the particle size and roughness of resting RAW264.7 macrophages, which suggested that PCs could activate resting RAW264.7 macrophages. And additionally, PCs-1 and PCs-2 were also found to reverse the surface particle size and roughness decrease of peritoneal macrophages isolated from cyclophosphamide induced immunosuppressive mice, suggesting the activation effects of PCs-1 and PCs-2 on immunosuppressive macrophages. These results further enhanced our understanding of macrophage activations by direct imaging of cell surface ultrastructure and also highlighted AFM as a novel nanotool for macrophage detections. And most importantly, these results also indicated the outstanding immunomodulatory effects of PCs on macrophages, which therefore suggested that PCs could be served as a kind of novel immunomodulatory agents that would benefit human health. SCANNING 38:792-801, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 27280954 TI - Atomic-Scale Molecular Dynamics Simulations of DNA-Polycation Complexes: Two Distinct Binding Patterns. AB - Synthetic cationic polymers represent a promising class of delivery vectors for gene therapy. Here, we employ atomistic molecular dynamics simulations to gain insight into the structure and properties of complexes of DNA with four linear polycations: polyethylenimine (PEI), poly-l-lysine (PLL), polyvinylamine (PVA), and polyallylamine (PAA). These polycations differ in their polymer geometries, protonation states, and hydrophobicities of their backbone chains. Overall, our results demonstrate for the first time the existence of two distinct patterns of binding of DNA with polycations. For PEI, PLL, and PAA, the complex is stabilized by the electrostatic attraction between protonated amine groups of the polycation and phosphate groups of DNA. In contrast, PVA demonstrates an alternative binding pattern as it gets embedded into the DNA major groove. It is likely that both the polymer topology and affinity of the backbone chain of PVA to the DNA groove are responsible for such behavior. The differences in binding patterns can have important biomedical implications: embedding PVA into a DNA groove makes it less sensitive to changes in the aqueous environment (pH level, ionic strength, etc.) and could therefore hinder the intracellular release of genetic material from a delivery vector, leading to lower transfection activity. PMID- 27280955 TI - A Simple Dual-pH Responsive Prodrug-Based Polymeric Micelles for Drug Delivery. AB - To precisely deliver drug molecules at a targeted site and in a controllable manner, there has been great interest in designing a synergistical drug delivery system that can achieve both surface charge-conversion and controlled release of a drug in response to different stimuli. Here we outline a simple method to construct an intelligent drug carrier, which can respond to two different pH values, therefore achieving charge conversion and chemical-bond-cleavage-induced drug release in a stepwise fashion. This drug carrier comes from the self assembly of a block copolymer-DOX conjugate synthesized through a Schiff base reaction between poly(2-(diisopropylamino)ethyl methacrylate-b-poly(4 formylphenyl methacrylate-co-polyethylene glycol monomethyl ether methacrylate) (PDPA-b-P(FPMA-co-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles reversed from negative to positive when encountering a weakly acidic environment due to the protonation of PDPA segments. In vitro cellular uptake measurement shows that the cellular uptake and internalization of the BCP-DOX micelles can be significantly enhanced at pH ~ 6.5. Moreover, this drug carrier exhibits a pH dependent drug release owing to the cleavage of the imine bond at pH < 5.5. With this dual-pH responsive feature, these micelles may have the ability to precisely deliver DOX to the cancer cells. PMID- 27280956 TI - Risk for congenital anomalies in offspring of childhood, adolescent and young adult cancer survivors. AB - Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population-based cohort study aimed to investigate the risk for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non-significantly, elevated compared to that in offspring of siblings (2.7%) [prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91-1.25]. When offspring of childhood and adolescent survivors (0 19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non-significantly increased (PR 1.17, 95% CI 0.92-1.49). No such increase existed for offspring of young adult survivors (20-34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83-1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955-1964: PR 2.77, 95% C I 1.26-6.11; and 1965-1974: PR 1.55, 95% C I 0.94 2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades. PMID- 27280957 TI - Novel antimicrobial peptides with promising activity against multidrug resistant Salmonella enterica serovar Choleraesuis and its stress response mechanism. AB - AIMS: To evaluate the antibacterial efficacy of novel antimicrobial peptides (AMPs) against multidrug-resistant (MDR) Salmonella enterica serovar Choleraesuis (Salm. Choleraesuis) and to delineate the AMP-responsive mechanisms of wild-type (WT) and MDR strains. METHODS AND RESULTS: Proteomic approaches were performed based on two-dimensional gel electrophoresis and liquid chromatography electrospray ionization-quadrupole- time-of-flight tandem mass spectrometry to analyse the protein profiles of these two strains upon exposure to AMP GW-Q6. Quantitative real-time PCR was conducted to determine the mRNA expression level of the target genes. Furthermore, lipopolysaccharide (LPS) competition analysis was used to verify whether LPS may serve as the potential binding target when AMP approach and adhere to the bacterial surface. CONCLUSIONS: The minimal inhibitory concentration assay revealed that our AMPs were even more effective against the MDR strains (4-32 MUg ml(-1) ), compared with those for the WT (8-64 MUg ml(-1) ). LPS dose-dependently suppressed the GW-Q6 antimicrobial activity. Clusters of orthologous groups analysis showed that the majority of the AMP-responsive proteins were involved in cell envelope biogenesis and outer membrane, translation and chaperones. SIGNIFICANCE AND IMPACT OF THE STUDY: These results indicated that the novel AMP GW-Q6 serves as a potential candidate for antimicrobial drug development against MDR strains. These findings will also be helpful for expanding our knowledge on the molecular mechanisms of AMP-microbe interaction and the pathogenicity of salmonellosis caused by MDR strains of Salm. Choleraesuis. PMID- 27280958 TI - Pregnancy Outcomes Based on Pre-Pregnancy Body Mass Index in Japanese Women. AB - OBJECTIVE: To verify whether body mass index (BMI) classification proposed by the Institute of Medicine (IOM) is valid in Japanese women. METHOD: A study was conducted in 97,157 women with singleton pregnancies registered in the Japan Society of Obstetrics and Gynecology (JSOG) Successive Pregnancy Birth Registry System between January 2013 and December 2013, to examine pregnancy outcomes in four groups stratified by pre-pregnancy BMI category according to the 2009 criteria recommended by the Institute of Medicine (IOM). The groups comprised 17,724 underweight women with BMI <18.5, 69,126 normal weight women with BMI 18.5 24.9, 7,502 overweight women with BMI 25-29.9, and 2,805 obese women with BMI >=30. The pregnancy outcomes were also compared among subgroups stratified by a gestational weight gain below, within, and above the optimal weight gain. RESULTS: The higher the pre-pregnancy BMI, the higher the incidences of pregnancy induced hypertension, gestational diabetes mellitus, macrosomia, cesarean delivery, postpartum hemorrhage, and post-term birth, but the lower the incidence of small for gestational age (SGA). In all pre-pregnancy BMI category groups, excess gestational weight gain was associated with a higher frequency of large for gestational age and macrosomia; poor weight gain correlated with a higher frequency of SGA, preterm birth, preterm premature rupture of membranes, and spontaneous preterm birth; and optimal weight gain within the recommended range was associated with a better outcome. CONCLUSION: The BMI classification by the IOM was demonstrated to be valid in Japanese women. PMID- 27280959 TI - Asymmetric Synthesis of Enantiomerically Pure Mono- and Binuclear Bis(cyclometalated) Iridium(III) Complexes. AB - Chiral precursors Lambda-[Ir(ppy)2(l-pro)] (Lambda-L, where ppy is 2 phenylpyridine; pro is proline), Lambda-[Ir(ppy)2(MeCN)2](PF6) (Lambda-1), Delta [Ir(ppy)2(d-pro)] (Delta-D), and Delta-[Ir(ppy)2(MeCN)2](PF6) (Delta-1) were synthesized from rac-[(Ir(ppy)2)2Cl2] and l-pro or d-pro by means of the auxiliary ligand strategy with 99% de values. The enantiopure mono complexes Lambda/Delta-[Ir(ppy)2(L)](PF6) (L is 2,2'-bipyridine, Lambda/Delta-2; L is 2,2' dipyrimidine (dpm), Lambda/Delta-3; L is 2,2'-bibenzimidazole (H2bbim), Lambda/Delta-4) with 99% ee values and binuclear complexes LambdaLambda/DeltaDelta-[(Ir(ppy)2)2(dpm)](PF6)2 (LambdaLambda-5 and DeltaDelta 5) and LambdaLambda/DeltaDelta-[(Ir(ppy)2)2(bbim)] (LambdaLambda-6 and DeltaDelta 6) with 99% de values were synthesized in one step using the corresponding chiral precursors. The absolute configurations at Ir(III) centers of precursor Delta-1, mononuclear Lambda-3, and binuclear DeltaDelta-6 were confirmed by single-crystal structural analysis and characterized by circular dichroism (CD) spectroscopy. The correlation between the absolute configuration at Ir(III) center and CD spectra was established. The configurations at Ir(III) centers are stable during the reactions, and the chiral precursors can be used for the asymmetric synthesis of enantiomerically pure mono- and polynuclear Ir(III) complexes. Moreover, meso LambdaDelta-[(Ir(ppy)2)2(dpm)](PF6)2 (meso-5) and LambdaDelta-[(Ir(ppy)2)2(bbim)] (meso-6) were also synthesized using these precursors. PMID- 27280960 TI - Effects of web-based stress and depression literacy intervention on improving symptoms and knowledge of depression among workers: A randomized controlled trial. AB - BACKGROUND: The present randomized controlled trial aimed to examine whether a newly developed psychoeducational information website on stress and depression was effective in improving depressive symptoms at one- and four-month follow-ups among workers in Japan. METHODS: Participants were recruited from registered members of a web survey site in Japan. Participants who fulfilled the eligibility criteria were randomly allocated to intervention or control groups. Immediately after the baseline survey, the intervention group was invited to access a psychoeducational website named the "UTSMed" within 4 months after the baseline survey. Depressive symptoms (Beck Depression Inventory II; BDI-II) were assessed as a primary outcome, at baseline, and one- and four-month follow-ups for both intervention and control groups. The analyses were conducted separately by the three subgroups (high-risk, moderate-risk, and low-risk). RESULTS: A total of 1236 workers completed the baseline survey. Participants were randomly allocated to an intervention or control group (N=618 for each), with the subgroups of high risk (7-8%), moderate-risk (47%) and low-risk (45-46%) in each group. A significant intervention effect on improving depressive symptoms (t=-2.35, P =0.02, d=-0.57) was observed at 1-month follow-up only in the high-risk subgroup. LIMITATIONS: The present study did not use a stratified permuted-block randomization. CONCLUSIONS: A web-based psychoeducation approach may not be effective enough in improving depressive symptoms in a general population of workers, while it may be effective for workers who had recently sought help for mental health. PMID- 27280961 TI - Influences of the Big Five personality traits on the treatment response and longitudinal course of depression in patients with acute coronary syndrome: A randomised controlled trial. AB - BACKGROUND: Influences of the Big Five personality traits on the treatment response and longitudinal course of depression in patients with acute coronary syndrome: A randomised controlled trial. METHODS: This naturalistic observational study initially recruited 1152 ACS patients; 685 patients completed personality assessments at baseline, of whom 630 were followed-up one year later. Of the 294 patients with depression, 207 participated in a 24-week double blind trial of escitalopram or placebo. The remaining 87 patients who received medical treatment only and the 391 who had not depression were also followed in a one year naturalistic observational study. The Big five personality traits were assessed using the Big Five Inventory. The influences of personality on the Hamilton Depression Rating Scale score changes were analysed using a mixed-model repeated measures analysis of covariance. RESULTS: A Cluster analysis identified two personality types: resilient and vulnerable. The vulnerable personality type was characterized by lower extraversion, agreeableness, and conscientiousness - but higher neuroticism - than the resilient type. This personality type was independently associated with a poorer outcome of depression in ACS patients during the 24-week treatment period and the one year longitudinal follow-up period compared to the resilient personality type, irrespective of treatment allocation. LIMITATIONS: Recruitment from a single institution may limit generalisability. Personality traits were investigated 12-weeks after ACS; thus, the responses may have been influenced by the prior receipt of escitalopram. CONCLUSIONS: Personality types influences the treatment outcome and longitudinal course of depression in ACS patients independent of antidepressant treatment. PMID- 27280963 TI - The effects of desvenlafaxine on neurocognitive and work functioning in employed outpatients with major depressive disorder. AB - BACKGROUND: Major depressive disorder (MDD) is associated with staggering personal and economic costs, a major proportion of which stem from impaired psychosocial and occupational functioning. Few studies have examined the impact of depression-related cognitive dysfunction on work functioning. We examined the association between neurocognitive and work functioning in employed patients with MDD. METHODS: Employed adult outpatients (n=36) with MDD of at least moderate severity (>=23 on the Montgomery Asberg Depression Rating Scale, MADRS) and subjective cognitive complaints completed neurocognitive tests (CNS Vital Signs computerized battery) and validated self-reports of their work functioning (LEAPS, HPQ) before and after 8 weeks of open-label treatment with flexibly-dosed desvenlafaxine 50-100mg/day. Relationships between neurocognitive tests and functional measures were examined using bivariate correlational and multiple regression analyses, as appropriate. An ANCOVA model examined whether significant change in neurocognitive performance, defined as improvement of >=1SD in the Neurocognition Index (NCI) from baseline to post-treatment, was associated with improved outcomes. RESULTS: Patients showed significant improvements in depressive symptom, neurocognitive, and work functioning measures following treatment with desvenlafaxine (e.g., MADRS response=77% and MADRS remission=49%). There were no significant correlations between changes in NCI or cognitive domain subscales and changes in MADRS, LEAPS, or HPQ scores. However, patients demonstrating significant improvement in NCI scores (n=11, 29%) had significantly greater improvement in clinical and work functioning outcomes compared to those without NCI improvement. LIMITATIONS: The limitations of this study include small sample size, lack of a placebo control group, and lack of a healthy comparison group. Our sample also had more years of education and higher premorbid intelligence than the general population. CONCLUSIONS: There were no significant correlations between changes in neurocognitive and work functioning measures in this study. However, meaningful improvement in neurocognitive functioning with desvenlafaxine was associated with greater improvement in both mood and occupational outcomes. This suggests that addressing cognitive dysfunction may improve clinical and occupational outcomes in employed patients with MDD. However, the relationship between neurocognitive and work functioning in MDD is complex and requires further study. PMID- 27280962 TI - Reversal-learning deficits in childhood-onset bipolar disorder across the transition from childhood to young adulthood. AB - BACKGROUND: Bipolar disorder (BD) is a severe mental illness that can have high costs for youths (<18 years old) and adults. Relative to healthy controls (HC), individuals with BD often show impaired attention, working memory, executive function, and cognitive flexibility (the ability to adapt to changing reward/punishment contingencies). In our study of youths and young adults with BD, we investigated 1) how cognitive flexibility varies developmentally in BD, and 2) whether it is independent of other executive function deficits associated with BD. METHODS: We measured errors on a reversal-learning task, as well as spatial working memory and other executive function, among participants with BD (N=75) and HC (N=130), 7-27 years old. Regression analyses focused on the effects of diagnosis on reversal-learning errors, controlling for age, gender, IQ, spatial span, and executive function. Similar analyses examined non-reversal errors to rule out general task impairment. RESULTS: Participants with BD, regardless of age, gender, or cognitive ability, showed more errors than HC on the response reversal stages of the cognitive flexibility task. However, participants with BD did not show more errors on non-reversal stages, even when controlling for other variables. LIMITATIONS: Study limitations include the cross sectional, rather than longitudinal, design; inability to measure non-linear age effects; and inclusion of medicated participants and those with psychiatric comorbidity. CONCLUSIONS: Individuals with BD show a specific impairment in reversing a previously rewarded response, which persists across the transition from childhood to young adulthood. Tailored interventions targeting this deficit may be effective throughout this developmentally turbulent time. PMID- 27280964 TI - Developmental trajectories of pregnant and postpartum depression in an epidemiologic survey. AB - OBJECTIVE: To estimate the prevalence and determinants for the peripartum depression. METHODS: Data were extracted from the 2 waves of the National Epidemiologic Study of Alcohol and Related Conditions (NESARC), a representative sample of the US population corresponding to 34,653 participants. All women pregnant during the year before the second assessment were included. Peripartum depression was evaluated according a semi-structured interview at Wave 2. Risk factors covering life from childhood through adulthood, and including sexual abuse, family history of depression and psychiatric disorder lifetime were evaluated at wave 1. Stressful life event and obstetric factors were evaluated for the period of 12 months preceding the second interview. RESULTS: In the sample of 1085 participants pregnant at wave 2, the prevalence of peripartum depression was 10.8%. Women with a peripartum depression reported higher rates of sexual abuse in childhood (OR=3.07), family history of depression (OR=3.27). A history of mental disorder was associated with a higher rate of peripartum depression (OR=3.43) Four disorders were specifically associated with higher rate of peripartum depression including depression (OR=4.91), substance use disorder (OR=2.37), bipolar disorder (OR=2.39) and history of suicide attempt (OR=3.79). Peripartum depression was associated with stressful life event in the last year (OR=3.03), and complications during pregnancy (OR=2.10). LIMITATIONS: Not distinguish between depressed women during pregnancy from postpartum depressed women. CONCLUSION: Depression affects more than one in 10 women during peripartum. The factors associated with peripartum depression are traumatic, personal or family history of mental disorder, in a timeframe covering life from childhood through adulthood. PMID- 27280965 TI - Alterations in regional homogeneity of resting-state brain activity in patients with major depressive disorder screening positive on the 32-item hypomania checklist (HCL-32). AB - BACKGROUND: Bipolar disorder (BD) is difficult to diagnose in the early stages of the illness, with the most frequent misdiagnosis being major depressive disorder (MDD). We aimed to use a regional homogeneity (ReHo) approach with resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the features of spontaneous brain activity in MDD patients screening positive on the 32-item Hypomania Checklist (HCL-32). METHODS: Nineteen MDD patients screening positive (HCL-32(+); 9 males; 24.9+/-5.7 years) and 18 patients screening negative (HCL 32(-); 9 males; 27.1+/-6.7 years), together with 24 healthy controls (HC; 11 males; 26.4+/-3.9 years) were studied. ReHo maps were compared and an receiver operating characteristic (ROC) analysis was conducted to confirm the utility of the identified ReHo differences in classifying the patients. RESULTS: The MDD versus HC showed different ReHo in many brain areas, especially in the frontal and parietal cortex. The HCL-32(+) versus HCL-32(-) showed significant increase of ReHo in the right medial superior frontal cortex, left inferior parietal cortex and middle/inferior temporal cortex, and decrease of ReHo in the left postcentral cortex and cerebellum. ROC analysis showed good sensitivity and specificity for distinguishing these two subgroups of MDD. LIMITATIONS: Recruited patients were all on antidepressants and standard mania rating scales were not performed to assess their hypomanic symptoms. CONCLUSIONS: The rs-fMRI measurement of ReHo in distributed brain regions may be putative biomarkers which could differentiate subthreshold BD from MDD. PMID- 27280967 TI - The aetiology and maintenance of social anxiety disorder: A synthesis of complimentary theoretical models and formulation of a new integrated model. AB - BACKGROUND: Within maintenance models of social anxiety disorder (SAD), a number of cognitive and behavioural factors that drive the persistence of SAD have been proposed. However, these maintenance models do not address how SAD develops, or the origins of the proposed maintaining factors. There are also models of the development of SAD that have been proposed independently from maintenance models. These models highlight multiple factors that contribute risk to the onset of SAD, but do not address how these aetiological factors may lead to the development of the maintaining factors associated with SAD. METHODS: A systematic review of the literature was conducted to identify aetiological and maintenance models of SAD. We then united key factors identified in these models and formulated an integrated aetiological and maintenance (IAM) model of SAD. A systematic review of the literature was then conducted on the components of the IAM model. RESULTS: A number of aetiological and maintaining factors were identified in models of SAD. These factors could be drawn together into the IAM model. On balance, there is empirical evidence for the association of each of the factors in the IAM model with social anxiety or SAD, providing preliminary support for the model. LIMITATIONS: There are relationships between components of the IAM model that require empirical attention. Future research will need to continue to test the IAM model. CONCLUSIONS: The IAM model provides a framework for future investigations into the development and persistence of SAD. PMID- 27280966 TI - Functional domains as correlates of suicidality among psychiatric inpatients. AB - BACKGROUND: Suicide remains poorly understood and unpredictable. Addressing this challenge, this study examined the independent contributions of several research domain criteria (RDoC) constructs in relation to suicidality in patients hospitalized for acute suicide risk. Specifically, we examined anhedonia, anxiety/entrapment, and attachment disturbances, reflecting disturbances in reward processes, negative valence systems, and social processes, respectively. METHODS: Anhedonia, anxiety, entrapment, and fearful attachment, were assessed quantitatively in 135 adults hospitalized for suicidality. Current suicidality and suicidal history were assessed with the Columbia Suicide Severity Rating Scale. Bivariate analyses (with significance threshold of p<.01 to account for multiple comparisons) and multivariate models examined relationships between symptom dimensions and severity of suicidal ideation (SI). We also assessed differences between patients with a history of suicide attempt and those who exhibited only suicidal ideations. RESULTS: Using bivariate analyses all symptoms except for fearful attachment correlated robustly with SI (r =.37-0.50, p<.001). However, when using multivariate analyses, only anhedonia (beta=.28, p=.01) and entrapment (beta=.19, p=.03) were independently associated with SI across the entire sample. No functional domain measures differed between patients with history of suicide attempt versus ideation only. LIMITATIONS: The reliance on self-report data and a cross-sectional design. CONCLUSIONS: Disturbances in reward and threat processing may represent independent factors in the development of suicidal ideation in this high suicide risk cohort. Future studies should assess their role as risk factors. PMID- 27280968 TI - Polycyclic Polyprenylated Acylphloroglucinol Congeners from Hypericum scabrum. AB - Twenty polycyclic polyprenylated acylphloroglucinols (PPAPs), including the new compounds hyperscabrones A-I (1-9), were isolated from the air-dried aerial parts of Hypericum scabrum. These compounds comprise seven different structural types. All structures were determined by NMR spectroscopic methods and both experimental and calculated electronic circular dichroism (ECD) spectra. The evaluation of their neuroprotective effects on glutamate-induced toxicity in SK-N-SH cells showed that compounds 4-7 exhibited significant neuroprotection at 10 MUM. Additionally, compounds 3, 4, 7, and 9 showed moderate hepatoprotective activities against paracetamol-induced HepG2 cell damage at 10 MUM. PMID- 27280969 TI - Photoinduced Charge Separation within Metallo-supramolecular Wires Built around a [Ru(bpy)3](2+)-Bisterpyridine Linear Entity. AB - A [Ru(bpy)3](2+)-like complex (L1) bearing two free terpyridine groups at the 5 and 5' positions of the same bipyridine, linked by the rigid and linear 2,5 dimethyl phenylene bridges has been synthesized to open access to two classes of linear molecular wires with photosensitive properties: a bimetallic coordination polymer and an inorganic triad. In this Research Article, we report on the synthesis and characterization of the resulting [{Ru(II_)Fe(II)}n](4n+) alternated bimetallic polymer and the [Co(III_)Ru(II_)Fe(II)](7+) triad based on the building block L1. The [{Ru(II_)Fe(II)}n](4n+) polymer is fully characterized in solution. Cyclic voltammetry and emission lifetime measurements show that the bridging ligand allows interaction between the metal centers in the excited state despite the lack of interactions in the ground state. Under visible irradiation, the polymer can be fully oxidized in the presence of a sacrificial electron acceptor in solution. Thin robust films of the polymer are easily obtained on ITO by a simple electrochemical procedure based on an electroreduction adsorption process. The ITO/[{Ru(II_)Fe(II)}n](4n+)-modified electrode behaves as a photocathode under irradiation in the presence of ArN2(+). The magnitude of the photocurrent is dependent on the film thickness, probably limited by the diffusion of charge in thicker film. On the other hand L1 is also used to construct a well-ordered triad in association with Co(III) and Fe(II) metallic centers as electron acceptor and donor, respectively. The metallic triad is anchored on ITO or on a SiO2 wafer, starting from a terpyridine phosphonate modified surface. AFM images prove the presence of the triad in a linear upward orientation. Irradiation of the ITO/[Co(III_)Ru(II_)Fe(II)](7+) modified surface in the presence of triethanolamine in CH3CN induces the generation of an anodic photocurrent of around 30 MUA.cm(-2). The photocurrent density generated by the ITO/[Co(III_)Ru(II_)Fe(II)](7+) electrode, appears to be more stable than in the case of ITO/[{Ru(II_)Fe(II)}n](4n+) because of the presence of the anchoring group. Moreover, this photocurrent magnitude represents an enhancement of 30% compared to our previous triad ( Dalton Trans. 2014 , 43 , 12156 - 12159 ), proving the advantage of a linear and rigid spacer for the construction of such molecular assemblies with photoinduced charge transfer abilities. PMID- 27280970 TI - Trafficking Dynamics of PCSK9-Induced LDLR Degradation: Focus on Human PCSK9 Mutations and C-Terminal Domain. AB - PCSK9 is a secreted ligand and negative post-translational regulator of low density lipoprotein receptor (LDLR) in hepatocytes. Gain-of-function (GOF) or loss-of-function (LOF) mutations in PCSK9 are directly correlated with high or low plasma LDL-cholesterol levels, respectively. Therefore, PCSK9 is a prevailing lipid-lowering target to prevent coronary heart diseases and stroke. Herein, we fused monomeric fluorescent proteins to PCSK9 and LDLR to visualize their intra- and extracellular trafficking dynamics by live confocal microscopy. Fluorescence recovery after photobleaching (FRAP) showed that PCSK9 LOF R46L mutant and GOF mutations S127R and D129G, but not the LDLR high-affinity mutant D374Y, significantly accelerate PCSK9 exit from the endoplasmic reticulum (ER). Quantitative analysis of inverse FRAP revealed that only R46L presented a much slower trafficking from the trans-Golgi network (TGN) to the plasma membrane and a lower mobile fraction likely suggesting accumulation or delayed exit at the TGN as an underlying mechanism. While not primarily involved in LDLR binding, PCSK9 C terminal domain (CTD) was found to be essential to induce LDLR degradation both upon its overexpression in cells or via the extracellular pathway. Our data revealed that PCSK9 CTD is required for the localization of PCSK9 at the TGN and increases its LDLR-mediated endocytosis. Interestingly, intracellular lysosomal targeting of PCSK9-DeltaCTD was able to rescue its capacity to induce LDLR degradation emphasizing a role of the CTD in the sorting of PCSK9-LDLR complex towards late endocytic compartments. Finally, we validated our dual fluorescence system as a cell based-assay by preventing PCSK9 internalization using a PCSK9 LDLR blocking antibody, which may be expended to identify protein, peptide or small molecule inhibitors of PCSK9. PMID- 27280971 TI - AAV Vectorization of DSB-mediated Gene Editing Technologies. AB - Recent work both at the bench and the bedside demonstrate zinc-finger nucleases (ZFNs), CRISPR/Cas9, and other programmable site-specific endonuclease technologies are being successfully utilized within and alongside AAV vectors to induce therapeutically relevant levels of directed gene editing within the human chromosome. Studies from past decades acknowledge that AAV vector genomes are enhanced substrates for homology-directed repair in the presence or absence of targeted DNA damage within the host genome. Additionally, AAV vectors are currently the most efficient format for in vivo gene delivery with no vector related complications in >100 clinical trials for diverse diseases. At the same time, advancements in the design of custom-engineered site-specific endonucleases and the utilization of elucidated endonuclease formats have resulted in efficient and facile genetic engineering for basic science and for clinical therapies. AAV vectors and gene editing technologies are an obvious marriage, using AAV for the delivery of repair substrate and/or a gene encoding a designer endonuclease; however, while efficient delivery and enhanced gene targeting by vector genomes are advantageous, other attributes of AAV vectors are less desirable for gene editing technologies. This review summarizes the various roles that AAV vectors play in gene editing technologies and provides insight into its trending applications for the treatment of genetic diseases. PMID- 27280972 TI - Gender-based violence against female sex workers in Cameroon: prevalence and associations with sexual HIV risk and access to health services and justice. AB - BACKGROUND/OBJECTIVES: Female sex workers (FSWs) are at risk for HIV and physical and sexual gender-based violence (GBV). We describe the prevalence of lifetime GBV and its associations with HIV risk behaviour, access to health services and barriers in accessing justice among FSWs in Cameroon. METHODS: FSWs (n=1817) were recruited for a cross-sectional study through snowball sampling in seven cities in Cameroon. We examined associations of lifetime GBV with key outcomes via adjusted logistic regression models. RESULTS: Overall, 60% (1098/1817) had experienced physical or sexual violence in their lifetime. GBV was associated with inconsistent condom use with clients (adjusted OR (AOR) 1.49, 95% CI 1.18 to 1.87), being offered more money for condomless sex (AOR 2.09, 95% CI 1.56 to 2.79), having had a condom slip or break (AOR 1.53, 95% CI 1.25 to 1.87) and difficulty suggesting condoms with non-paying partners (AOR 1.47, 95% CI 1.16 to 1.87). Violence was also associated with fear of health services (AOR 2.25, 95% CI 1.61 to 3.16) and mistreatment in a health centre (AOR 1.66, 95% CI 1.01 to 2.73). Access to justice was constrained for FSWs with a GBV history, specifically feeling that police did not protect them (AOR 1.41, 95% CI 1.12 to 1.78). DISCUSSION: Among FSWs in Cameroon, violence is prevalent and undermines HIV prevention and access to healthcare and justice. Violence is highly relevant to FSWs' ability to successfully negotiate condom use and engage in healthcare. In this setting of criminalised sex work, an integrated, multisectoral GBV-HIV strategy that attends to structural risk is needed to enhance safety, HIV prevention and access to care and justice. PMID- 27280973 TI - Persuading People to Drink Less Alcohol: The Role of Message Framing, Temporal Focus and Autonomy. AB - AIMS: Health information can be used to try to persuade people to follow safe drinking recommendations. However, both the framing of information and the dispositional characteristics of message recipients need to be considered. An online study was conducted to examine how level of autonomy moderated the effect on drinking behaviour of gain- and loss-framed messages about the short- vs. long term consequences of alcohol use. METHODS: At Time 1, participants (N = 335) provided demographic information and completed a measure of autonomy. At Time 2, participants reported baseline alcohol use and read a gain-framed or loss-framed health message that highlighted either short- or long-term outcomes of alcohol consumption. Alcohol consumption was reported 7 days later. RESULTS: The results showed a significant three-way interaction between message framing (loss vs. gain), temporal focus (short-term vs. long-term) and autonomy. For low-autonomy (but not high-autonomy) individuals, the loss-framed health message was associated with lower levels of alcohol consumption than was the gain-framed message but only if the short-term outcomes were conveyed. CONCLUSION: This research provides evidence that the interaction between message framing and temporal focus may depend on a person's level of autonomy, which has implications for health promotion and the construction of effective health communication messages. SHORT SUMMARY: We examined how autonomy moderated the effect on drinking behaviour of gain- and loss-framed messages about the short- vs. long term consequences of alcohol use. For low-autonomy individuals, the loss-framed health message was associated with lower alcohol consumption than was the gain framed message but only if the short-term outcomes were conveyed. PMID- 27280974 TI - Principles of start codon recognition in eukaryotic translation initiation. AB - Selection of the correct start codon during initiation of translation on the ribosome is a key event in protein synthesis. In eukaryotic initiation, several factors have to function in concert to ensure that the initiator tRNA finds the cognate AUG start codon during mRNA scanning. The two initiation factors eIF1 and eIF1A are known to provide important functions for the initiation process and codon selection. Here, we have used molecular dynamics free energy calculations to evaluate the energetics of initiator tRNA binding to different near-cognate codons on the yeast 40S ribosomal subunit, in the presence and absence of these two initiation factors. The results show that eIF1 and eIF1A together cause a relatively uniform and high discrimination against near-cognate codons. This works such that eIF1 boosts the discrimination against a first position near cognate G-U mismatch, and also against a second position A-A base pair, while eIF1A mainly acts on third codon position. The computer simulations further reveal the structural basis of the increased discriminatory effect caused by binding of eIF1 and eIF1A to the 40S ribosomal subunit. PMID- 27280975 TI - Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks. AB - Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. PMID- 27280976 TI - Imaging HIV-1 RNA dimerization in cells by multicolor super-resolution and fluctuation microscopies. AB - Dimerization is a unique and vital characteristic of retroviral genomes. It is commonly accepted that genomic RNA (gRNA) must be dimeric at the plasma membrane of the infected cells to be packaged during virus assembly. However, where, when and how HIV-1 gRNA find each other and dimerize in the cell are long-standing questions that cannot be answered using conventional approaches. Here, we combine two state-of-the-art, multicolor RNA labeling strategies with two single-molecule microscopy technologies to address these questions. We used 3D-super-resolution structured illumination microscopy to analyze and quantify the spatial gRNA association throughout the cell and monitored the dynamics of RNA-RNA complexes in living-cells by cross-correlation fluctuation analysis. These sensitive and complementary approaches, combined with trans-complementation experiments, reveal for the first time the presence of interacting gRNA in the cytosol, a challenging observation due to the low frequency of these events and their dilution among the bulk of other RNAs, and allow the determination of the subcellular orchestration of the HIV-1 dimerization process. PMID- 27280977 TI - Probing the impact of chromatin conformation on genome editing tools. AB - Transcription activator-like effector nucleases (TALENs) and RNA-guided nucleases derived from clustered, regularly interspaced, short palindromic repeats (CRISPR) Cas9 systems have become ubiquitous genome editing tools. Despite this, the impact that distinct high-order chromatin conformations have on these sequence specific designer nucleases is, presently, ill-defined. The same applies to the relative performance of TALENs and CRISPR/Cas9 nucleases at isogenic target sequences subjected to different epigenetic modifications. Here, to address these gaps in our knowledge, we have implemented quantitative cellular systems based on genetic reporters in which the euchromatic and heterochromatic statuses of designer nuclease target sites are stringently controlled by small-molecule drug availability. By using these systems, we demonstrate that TALENs and CRISPR/Cas9 nucleases are both significantly affected by the high-order epigenetic context of their target sequences. In addition, this outcome could also be ascertained for S. pyogenes CRISPR/Cas9 complexes harbouring Cas9 variants whose DNA cleaving specificities are superior to that of the wild-type Cas9 protein. Thus, the herein investigated cellular models will serve as valuable functional readouts for screening and assessing the role of chromatin on designer nucleases based on different platforms or with different architectures or compositions. PMID- 27280978 TI - Explaining the disease phenotype of intergenic SNP through predicted long range regulation. AB - Thousands of disease-associated SNPs (daSNPs) are located in intergenic regions (IGR), making it difficult to understand their association with disease phenotypes. Recent analysis found that non-coding daSNPs were frequently located in or approximate to regulatory elements, inspiring us to try to explain the disease phenotypes of IGR daSNPs through nearby regulatory sequences. Hence, after locating the nearest distal regulatory element (DRE) to a given IGR daSNP, we applied a computational method named INTREPID to predict the target genes regulated by the DRE, and then investigated their functional relevance to the IGR daSNP's disease phenotypes. 36.8% of all IGR daSNP-disease phenotype associations investigated were possibly explainable through the predicted target genes, which were enriched with, were functionally relevant to, or consisted of the corresponding disease genes. This proportion could be further increased to 60.5% if the LD SNPs of daSNPs were also considered. Furthermore, the predicted SNP target gene pairs were enriched with known eQTL/mQTL SNP-gene relationships. Overall, it's likely that IGR daSNPs may contribute to disease phenotypes by interfering with the regulatory function of their nearby DREs and causing abnormal expression of disease genes. PMID- 27280979 TI - Moving National Breastfeeding Policies into Practice: A Plea to Integrate Lactation Education and Training into Nutrition and Dietetics Programs in the United States. AB - In 2011, the Surgeon General's Call to Action to Support Breastfeeding called on all health professional organizations, medical schools, and credentialing boards to establish and incorporate minimum lactation education and training requirements into their credentialing, licensing, and certification processes and to include breastfeeding education in undergraduate and graduate education and training programs. Given the commonalities between the fields of nutrition and breastfeeding, it has been proposed that nutrition professionals are an underutilized resource in the field of lactation management. Considering the lack of breastfeeding knowledge and skills among health professionals, nutrition professionals should be afforded opportunities to learn lactation management during their studies. The United States Breastfeeding Committee published Core Competencies in Breastfeeding Care and Services for All Health Professionals in 2010. However, professional nutrition and lactation credentialing boards should cooperate to integrate mandatory minimum standards of lactation education for nutrition professionals. Undergraduate and graduate programs in nutrition and dietetics should incorporate lactation content into their core curricula to comply with such standards. In addition, dietetics programs should offer optional clinical lactation experiences for students who aspire to become an International Board Certified Lactation Consultant. PMID- 27280980 TI - Tackling Drug-Resistant Tuberculosis: Current Trends and Approaches. AB - Tuberculosis is very much rampant in our society and accounts for a large number of deaths annually. In spite of consistent efforts being made, the disease has not been curtailed yet. The emergence of MDR and XDR strains in the society along with an increase in the number of HIV cases and that of latent TB, have further aggravated the problem making the disease very much persistent. The current situation clearly manifests the need to discover and develop new potent molecules/approaches that could help to tackle drug resistance. Various molecules, such as derivatives of fluoroquinolones (e.g. gatifloxacin, moxifloxacin and DC-159a), rifamycins (rifapentine), oxazolidinones (linezolid, sutezolid/PNU-100480), diarylquinolines (TMC207/bedaquiline), antifungal azoles, pyrrole (LL3858), nitroimidazopyran (PA824), nitroimidazole (OPC67683, TBA-354), diamine (SQ109) and benzothiazinone (BTZ043) are being developed in an attempt to combat the disease. This review presents a general introduction to the current status of the disease, the biology of the pathogen as well as the state of drug development against tuberculosis (TB) with emphasis on the major problems and bottlenecks associated with the same. Starting from the first drug against TB, the review discusses the entire history and the course of development of the drugs which are available today in the market as well as those which are under various phases of clinical and pre-clinical trials along with their mechanism of action. It also talks about the possible role of nanosciences in combating TB. PMID- 27280982 TI - Canonical Discriminant Analysis Applied to the Headspace GC Profiles of Coffee Cultivars. AB - Chemometric methods were applied for analyzing the relationship between the classification of coffee cultivars and their volatile components. Six typical cultivars were selected from Coffea arabica L., and their headspace profiles were analyzed by GC and GC/MS. A canonical discriminant analysis, with GC peaks as the variables, suggested the existence of a relationship between the sensory characteristics and canonical variables. The six coffee cultivars were divided into three groups, respectively having a roasted note, sweet aroma and fermented odor. It is suggested that Brazil and Mandheling varieties had a roasted note derived from methylpyrazine, while Mocha coffee had a fermented odor derived from 2,3-butanedione. PMID- 27280981 TI - Redefining the Australian Anthrax Belt: Modeling the Ecological Niche and Predicting the Geographic Distribution of Bacillus anthracis. AB - The ecology and distribution of B. anthracis in Australia is not well understood, despite the continued occurrence of anthrax outbreaks in the eastern states of the country. Efforts to estimate the spatial extent of the risk of disease have been limited to a qualitative definition of an anthrax belt extending from southeast Queensland through the centre of New South Wales and into northern Victoria. This definition of the anthrax belt does not consider the role of environmental conditions in the distribution of B. anthracis. Here, we used the genetic algorithm for rule-set prediction model system (GARP), historical anthrax outbreaks and environmental data to model the ecological niche of B. anthracis and predict its potential geographic distribution in Australia. Our models reveal the niche of B. anthracis in Australia is characterized by a narrow range of ecological conditions concentrated in two disjunct corridors. The most dominant corridor, used to redefine a new anthrax belt, parallels the Eastern Highlands and runs from north Victoria to central east Queensland through the centre of New South Wales. This study has redefined the anthrax belt in eastern Australia and provides insights about the ecological factors that limit the distribution of B. anthracis at the continental scale for Australia. The geographic distributions identified can help inform anthrax surveillance strategies by public and veterinary health agencies. PMID- 27280983 TI - Storage of Shredded Cabbage under a Dynamically Controlled Atmosphere of High O2 and High CO2. AB - Shredded cabbage (Brassica oleracea L., Capitata group) was stored under a dynamically controlled atmosphere (DCA) and modified atmosphere (MA) at 5 degrees C. Quality factors were measured every 2 days. Browning was suppressed as the CO2 concentration was increased (0% to 15%), with no influence from O2 concentration (2.5% to 10%). The development of an off-odor was markedly delayed with an increase in O2 concentration, such an odor being detected after 6 days at 2.5% O2,8 to 10 days at 5% to 7.5% O2, and not at all above 10 days at 10% O2, while the off-odor development was little affected by CO2 concentration (5% to 15%). Total sugar, polyphenolics, total ascorbate, and total microbial count were little influenced by O2 and CO2. These results show that shredded cabbage can be kept in good condition with a combined high O2 and high CO2 atmosphere. These findings are largely different from those for MA storage. PMID- 27280984 TI - Sulfated N-Myristoyl Chitosan as a Surface Modifier of Liposomes. AB - Sulfated N-myristoyl chitosan (S-M-chitosan), which is strongly electrolytic and water soluble as well as partly hydrophobic due to long alkyl chains, was synthesized to be used as a liposome-surface modifier. The effects of the treatment with an aqueous S-M-chitosan solution on the stability of the liposome suspension prepared from hydrogenated egg yolk lecithin were examined on several points. A suspension of large liposomes prepared by the Bangham method was precipitated by standing for a day, but the precipitation was restrained when the sample was treated with S-M-chitosan solution. The turbidity of a small liposome suspension was changed greatly after the suspension was freeze-thawed, but the change was small in the treated sample. A similar result was obtained when the suspension was freeze-dried following the addition of water. These results come from the facts that the surface of the liposome was coated with S-M-chitosan and negatively charged as ascertained by the measurement of zeta potential and the electron microscopic observation. The repulsive force between charges was considered to be the origin of the stabilization. It was also shown from an ESR experiment that the treatment suppressed the elution rate of the material incorporated into the liposomes. PMID- 27280985 TI - Mn(2+) in D-Glucosaminate Dehydratase from Pseudomonas fluorescens. AB - D-Glucosaminate (D-GlcNA) dehydratase from Pseudomonas fluorescens was inhibited stoichiometrically by metal-chelating agents (EDTA, 8-hydroxyquinoline-5-sulfonic acid, alpha,alpha'-dipyridyl and o-phenan-throline). The activity of EDTA-treated enzyme was restored by incubation with Mn(2+) (0.4mM) or Ca(2+) (2mM) in the presence of pyridoxal 5'-phosphate (PLP, 0.2mM) in veronal buffer (VB, 40 mM, pH 8) at 37 degrees C for 30 min. The atomic absorption spectrum of the native enzyme showed that the enzyme contained 1 mol of Mn(2+) per mole of enzyme. Although the EDTA-treated enzyme was unstable at 4 degrees C, addition of Mn(2+) and PLP to the solution of the EDTA-treated enzyme prevented the inactivation. The Km of the restored enzyme for D-GlcNA was somewhat lower than that of the original enzyme. However, the Km for PLP increased 14-fold. These results suggest that D-GlcNA dehydratase contains Mn(2+) near the PLP-binding site, and the metal ion appears to stabilize the structure of the active site. PMID- 27280986 TI - Purification of Pyruvate Dehydrogenase Complex from an Extreme Thermophile, Bacillus caldolyticus, and Its Thermal Stability. AB - Pyruvate dehydrogenase multienzyme complex was purified from Bacillus caldolyticus. The complex was composed of four polypeptides with molecular masses of 39.8, 41.7, 53.7, and 57.5kDa estimated by SDS-PAGE and they were presumed to be pyruvate decarboxylase (E1, dimeric), lipoate acetyltransferase (E2), and lipoamide dehydrogenase (E3) on the analogy of those from Bacillus stearothermophilus. E1 and E3 were stable at pH 5.7-10.2 and 4.5-11.3, respectively. Halves of E1 and E3 activity were abolished by incubation for 30min at 65 degrees C and 85 degrees C, respectively. Loss of overall activity was principally due to inactivation of E1. Structural changes in the complex incubated at high temperature were studied by fluorescence spectroscopy. The results suggested that the thermal denaturation of the complex proceeded through at least two different steps: inactivations of E1 and E3, and the former process is accompanied by a reduction of the complex size. PMID- 27280988 TI - Measurement of the Thermal Conductivity of Unfrozen and Frozen Food Materials by a Steady State Method with Coaxial Dual-cylinder Apparatus. AB - Coaxial dual-cylinder apparatus was used to measure the effective thermal conductivity of aqueous solutions of glucose, sucrose, gelatin and egg albumin over a temperature range from -20 degrees to 20 degrees C by the steady state method. The accuracy of the apparatus was confirmed by testing with water and ice. The effective thermal conductivity decreased with an increase in the total solid content in both the frozen and unfrozen states. In the unfrozen state, the effective thermal conductivity was slightly dependent on temperature. In the frozen state, however, the effective thermal conductivity was strongly dependent on temperature; lower temperatures gave higher effective thermal conductivity, reflecting the increase in the ice fration. For the unfrozen samples, the intrinsic thermal conductivity of each solid component was calculated by heat transfer models. All the models tested, series, parallel and Maxwell-Eucken, were equally applicable to describe the heat conduction in the unfrozen state. In the frozen state, however, the strong temperature dependency of the effective thermal conductivity suggests that the effect of the temperature dependency of the ice fraction should be incorporated into theoretical models. PMID- 27280987 TI - Purification of Chymotrypsin Inhibitors from Larval Hemolymph of the Silkworm, Bombyx mori. AB - Chymotrypsin inhibitors were purified from larval hemolymph of Bombyx mori. The purification steps involved ammonium sulfate fractionation (30-70%) and liquid chromatography on Butyl-Toyopearl 650M, Sephadex G-75, concanavalin A-Sepharose, Mono-Q, and Mono-S columns. Fourteen isoforms of chymotrypsin inhibitor were resolved in hybrid crosses: ten isoforms from c60 * n511, eight from k03 * FJl, and nine from i10 * p50. Chromatographic and electrophoretic studies on the inhibitors suggested that they were expressed co-dominantly and could be classified into three molecular-size groups: 8-13 kDa, 40 kDa, and 42kDa. CI-b4, CI-13a, CI-13b, and CI-13c in the first group, CI-3 in the second group, and CI-8 in the third group were present in all of the hybrids. Inhibitors in the third size group had an affinity for concanavalin A-Sepharose. It was found that CI-13 was composed of three different inhibitors. PMID- 27280989 TI - Nitrate Reduction in Bacillus licheniformis in the Presence of Ammonium Salt by Shaking Culture. AB - A nitrate-reducing bacterium was isolated from a hot spring and identified as Bacillus licheniformis. This strain was found to accumulate NO2(-) in the medium even in the presence of NH4(+) by shaking culture when FeSO4 was added to the medium. The NO2(-) accumulation was due to nitrate reductase activity, and the same accumulation was also recognized in some other bacteria. Since the nitrate reduction had no marked effect on the cell growth, it is possible that this nitrate reduction may not be involved in either an assimilatory or a dissimilatory one like those hitherto reported. PMID- 27280990 TI - Relationship between the Thermal Denaturation and Gelling Properties of Legumin from Broad Beans. AB - The effects of NaCl and heating temperature on the gel-forming ability of legumin were studied. The addition of NaCl progressively increased the denaturation temperature of legumin. Heating to around the denaturation point, i.e., below the onset temperature (zone 1), between the onset and maximal temperatures (zone 2), between the maximal and final temperatures (zone 3), and above the final temperature (zone 4), affected both the gel-forming ability and gel properties. No gel was formed in zone 1, while the gel was harder in zone 3 than in zones 2 and 4. The gel hardness gradually decreased with increasing temperature in zone 4. Differences in the viscoelastic and microstructural properties between gels heated at various temperatures around the denaturation point were observed. PMID- 27280991 TI - High-pressure Sterilization of Ice Nucleation-active Xanthomonas campestris and Its Application to Egg Processing. AB - Xanthomonas campestris INXC-1 is able to freeze water at a subzero temperature higher than -5 degrees C. High-pressure treatment at 300 MPa and 5 degrees C for 5 min killed the cells without affecting their ice-nucleation activity. Egg white containing the pressurized cells began to freeze with a slight degree of supercooling. Ice crystals with a dendritic structure were formed when the egg white froze in the presence of the killed bacterial cells. The frozen egg white thawed more quickly than egg white frozen without the cells. PMID- 27280992 TI - Formation of Flower Fragrance Compounds from Their Precursors by Enzymic Action during Flower Opening. AB - Flower fragrance compounds were found to be produced from the precursor solution obtained from flower buds by crude enzyme prepared from the flowers at the opening stage. GC and GC-MS analyses showed the formation of volatile aroma constituents from the precursor solution of Jasminum polyanthum F, Jasminum sambac Ait, and Gardenia jasminoides E, but none in the case of Osmanthus fragrans L. The aroma-producing enzyme activity of G. jasminoides rapidly increased to reach the maximum at flower opening stage (stage 4) and decreased within 24 h after flower opening (stage 5). Fragrance precursors of G. jasminoides were suggested not to be mainly beta-glucosides of linalool, eugenol, borneol, and isoeugenol based on the results after beta-glucosidase and naringinase treatment of the precursor solution. The activity of hydrolytic enzyme(s) such as glycosidase was found to elevate during flower opening to result in the aroma formation. PMID- 27280993 TI - Substrate Specificity of Rat Plasma Lecithin-cholesterol Acyltransferase towards a Molecular Species of Phosphatidylcholine. AB - The substrate specificity and the affinity of rat purified lecithin-cholesterol acyltransferase towards the molecular species of phosphatidylcholine (PC) were studied in comparison with the human enzyme. The substrate vesicles were prepared with 40% of a test PC, 60% of egg yolk PC, and tritium cholesterol. Both human and rat enzymes showed similar high reactivity to the substrates containing three major PCs (16: 0-18: 1 PC, 16: 0-18: 2 PC, and 18: 0-18: 1 PC) of egg yolk compared with the vesicles of egg yolk PC alone. In the case of 18: 0-20: 4 PC, the rat enzyme had the highest activity among all the test PCs, but the human enzyme only had a moderate activity. Even when the substrate consisted of 18: 0 20: 4 PC alone, the rat enzyme had a high activity, but the activity of the human enzyme was not detected. Symmetrical diacyl-PCs (18: 2-18: 2 PC, 18: 1-18: 1 PC, 18: 0-18: 0 PC) were not a preferable substrate for either enzyme. The transfer of both the human and rat enzymes from the vesicles containing 18: 0-20: 4 PC to the egg yolk PC vesicles was on a higher level than that from the vesicles containing 18: 2-18: 2 PC. This suggests that the activity of the LCA T can be easily influenced by the kinds of PC molecular species and its relative content in the substrate and that the substrate may provide the extent of the enzyme transfer between the substrate particles. PMID- 27280994 TI - Measurement of Intracellular Ionized Calcium in a Free-living Soil Nematode, Caenorhabditis elegans. AB - A calcium chelating fluorescence indicator, fura-2, was used to measure intracellular ionized calcium in Caenorhabditis elegans. The indicator loading process was harmless to the nematode, and completed within 2-3 h. Fura-2 was loaded mainly at its intestinal tract. The effects of DOPA on locomotion and the level of intracellular calcium were investigated and measured by using a microfluorometer. The addition of DOPA temporarily increased [Ca(2+)]i for several minutes. PMID- 27280995 TI - A Highly Denaturant-durable Alginate Lyase from a Marine Bacterium: Purification and Properties. AB - Poly(alpha-L-guluronate)lyase, which depolymerizes polyguluronate of alginate, was purified from the culture medium of a marine bacterium isolated from the intestine contents of a red sea bream, Pagrus major. The enzyme was homogeneous as judged by polyacrylamide gel electrophoresis in the presence and absence of SDS and the molecular weight of 42,000 and 40,000 on SDS gel electrophoresis and on a Sephacryl S200HR column chromatography, respectively. The activity of the enzyme was higher at around pH 8.5 and stable from pH 6-10. The active form of the enzyme, which has been thought to be once lost upon incubation of the enzyme at higher temperatures up to 80 degrees C could be restored on cooling the enzyme. The residual activity was 45% even at 100 degrees C. By treatment with other denaturants, the activity was maintained in 3% SDS and was 70% in 6M GHCI and 60% in 4M urea on incubation at 25 degrees C for 30 min. In addition, several chemical. reagents were tested for the relationship between the functional amino acid residue and the active form of the enzyme. PMID- 27280996 TI - Purification and Characterization of Geranylgeranyl Diphosphate Synthase from Methanobacterium thermoformicicum SF-4. AB - Geranylgeranyl diphosphate (GGPP) synthase [EC 2.5.1.29] was purified to homogeneity from Methanobacterium thermoformicicum SF-4. The enzyme was a dimeric protein consisting of two identical subunits (Mr = 39,000) and catalyzed prenyl transfer reactions using isopentenyl diphosphate (Km = 30.8 MUM) and either dimethylallyl diphosphate (Km=16.8 MUM), geranyl diphosphate (Km=12.6 MUM), or farnesyl diphosphate (Km=14.7 MUM) as allylic partners. During a sequential elongation, C5->C10->C15->C20' intermediates were accumulated with various ratios to the final product GGPP. In the presence of 0.8 M KCl, GGPP synthease activity was greatly enhanced, stabilized to heat treatment at 65 degrees C for 30 min, and protected from inhibition by p-chloromercuribenzoic acid. No other prenyltransferase synthesizing C20 or shorter prenyl diphosphate was observed in M. thermoformicicum SF-4. These suggest that GGPP synthase alone is important in the biosynthetic pathways to squalene and membrane polar lipids at a chain elongation stage in this strain. PMID- 27280997 TI - Liver-specific Induction of NADPH-generating Enzymes by Polychlorinated Biphenyls in Rats. AB - The induction of NADPH-generating enzymes by polychlorinated biphenyls (PCB) in rats was investigated. The administration of PCB to rats for 3 and 14 days increased the activities of malic enzyme (ME, EC 1.1.1.40), glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49), and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44) about 2-fold above the control level in the liver. Hepatic mRNA levels of ME, G6PD, and 6PGD, except for G6PD mRNA of the 14-day group, were also elevated to the same degree as the enzyme activities in PCB-treated rats. In rats fed a PCB-containing diet for 1 day, the hepatic mRNA levels of ME and G6PD were elevated prior to the induction of enzyme activity. In the kidney, lung, spleen, heart, and testis, the mRNA levels of ME, G6PD, and 6PGD were not affected by PCB. The induction of hepatic NADPH-generating enzymes would imply an increased demand of NADPH in the liver of rats fed with a PCB-containing diet. PMID- 27280998 TI - Synthesis of (+)-Turmeronol A, an Inhibitor of Soybean Lipoxygenase, and (+)-ar Turmerone. AB - Syntheses of optically pure turmeronol A and turmerone were achieved in a simple manner starting from ethyl (R)-3-hydroxybutanoate (4) of 100% e.e. The key step was the displacement of the chiral tosylate (6) with an organocopper reagent. PMID- 27280999 TI - Characteristic and Localization of the Monitor Peptide Receptor. AB - The monitor peptide receptor in the small intestine was investigated. The receptor is on the intestinal mucosal cells [Biochem. J., in press]. The specific binding of the (125)I labeled monitor peptide to dispersed rat small intestinal cells was inhibited by treatment with p-toluensulfonyl-L-lysine chloromethyl ketone (TLCK), an affinity labeling reagent for trypsin. Soybean trypsin inhibitor (SBTI) did not inhibit the binding. Analysis with reduced SDS electrophoresis-autoradiography indicated that an affinity-cross-linked complex of the (125)I labeled monitor peptide and the receptor was abolished by the TLCK treatment but was not affected by the presence of SBTI. Histochemical studies found a predominatnt binding of (125)I labeled monitor peptide on cholecystokinin (CCK)-immunoreactive cells in tissue sections of the rat upper intestine. The result suggests that the monitor peptide receptor is on the surface of CCK producing cells. PMID- 27281000 TI - Studies on Cellular Response of Escherichia coli to UDP-Galactose Accumulation. AB - Cellular responses to intracellular accumulation of UDP-galactose (UDP-Gal) were investigated for D-galactose-induced lysis of an Escherichia coli galE mutant. The mutant, ara-207, showed dramatic lysis in a nutrient broth supplemented with D-galactose after 3h of cultivation when transformation of normal rod cells into bulged- and spheroplast-like cells was clearly observed under electron microscope. UDP-Gal had been already detected with the optimal level at 2 h of cultivation, followed by a drastic decrease in its level as well as a significant increase in the level of active (inhibitor-free) UDP-sugar hydrolase (USH) together with the bacterial lysis. Significant loss of UTP, UDP, and UDP-N acetylglucosamine agreed with the in vivo activity of USH thus produced. Addition of D-sorbitol did not restrict UDP-Gal accumulation but did mostly protect ara 207 against the above morphological changes of the cells in which overproduction of USH was repressed over 3 to 4 h of cultivation. These results suggested that accumulation of UDP-Gal could have some growth inhibitory effect on E. coli cells but the compound was not directly involved with the following lytic process via spheroplast formation. A possibility was taken into account, that the accumulation of UDP-Gal caused overproduction of USH, which may provoke inhibition of bacterial peptidoglycan synthesis. PMID- 27281001 TI - Characterization and Thermostability of a Membrane-bound Hydrogenase from a Thermophilic Hydrogen Oxidizing Bacterium, Bacillus schlegelii. PMID- 27281002 TI - A New Method for Precipitation of Various Glucosides with Cyclodextrin Glucanotransferase. PMID- 27281003 TI - Suppression of Plasma Cholesterol Elevation by Okara Tempe in Rats. AB - Okara Tempe (OT), an Indonesian fermented traditional food, which is the fermented okara (insoluble residues of homogenized soybean, OC) by Rhizopus oligosporus, and which is interested in as a new high fiber and low energy soybean foodstuff. In this study, the effects of protein and dietary fiber (DF) of OT on sterol metabolism in rats were investigated. When rats were fed by OT or casein as protein source, the cholesterol and bile acid levels in plasma was significantly lower in OT fed group than in casein fed group. When rats were fed by OT or OC as DF source, in OT fed group, the cholesterol and bile acid levels in plasma was similar to them in OC fed group, but the cholesterol level in liver was lower than it in OC fed group, and the excretion of cholesterol and bile acid in feces was larger than in OC fed group. These results suggest that the cholesterol lowering action of OT in plasma would arise from the complementary action of protein and water soluble DF in OT. PMID- 27281004 TI - HPLC Measurement of the Uronate and Neutral Sugar Contents in Corn Hemicellulose. PMID- 27281005 TI - Assignment of the Absolute Configuration of Partially Methylated Galactoses by Combined Gas-liquid Chromatography-Mass Spectrometry. PMID- 27281006 TI - Binding of an Engineered 130-kDa Insecticidal Protein of Bacillus thuringiensis var. israelensis to Insect Cell Lines. PMID- 27281007 TI - Peroxyl Radical Scavenging Activity of Caffeic Acid and Its Related Phenolic Compounds in Solution. PMID- 27281008 TI - Production of Phenolic Compounds by Aspergillus S-4 in Sake Cake Medium and Identification of Terrein. AB - High performance liquid chromatography (HPLC) analysis of the culture filtrate of an isolated mold, Aspergillus terreus S-4, showed a larger peak of a terrein-like substance than those of gallic acid and protocatechuic acid. The chemical structure of this substance was investigated and identified as terrein, 4,5 dihydroxy-3-propenyl- 2-cyclopenten-1-one. We also examined some culture conditions for the production of terrein using a sake cake medium for strain S-4. PMID- 27281009 TI - Enzymatic Preparation of Aromatic Ethylamines from Aromatic L-Amino Acids. PMID- 27281010 TI - Production of Poly(gamma-glutamic acid) by Bacillus subtilis F-2-01. PMID- 27281011 TI - Structures of Antafumicins A and B, Novel Antifungal Substances Produced by the Fungus Aspergillus niger NH-401. AB - Novel antifungal substances, antafumicins A and B, were isolated from a culture of Aspergillus niger NH-401 and determined to be trans- and cis-4-(3-acetyl-2,6 dihydroxyphenyl)-2-methoxy-4- butanolide, respectively, by spectroscopic and single crystal X-ray analyses. PMID- 27281012 TI - Novel Cyclic Dextrins, Cycloisomaltooligosaccharides, from Bacillus sp. T-3040 Culture. AB - Three kinds of novel cyclic isomaltooligosaccharides were isolated from the culture broth of a strain of Bacillus sp. T-3040, which had been isolated from soil. They were identified as cycloisomalto-heptaose, -octaose, and -nonaose, respectively, on the basis of their mass spectra, proton nuclear magnetic resonance spectra, carbon nuclear magnetic resonance spectra, infrared spectra, reducing power, and results of enzymatic analysis using endo-dextranase and exo dextranase. They also showed features similar to cyclodextrins upon high-pressure liquid chromatography analysis using an ODS column. PMID- 27281013 TI - Expanding Roles and Broader Goals for Global Surgery. PMID- 27281014 TI - Feline Mammary Cancer. AB - Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern of metastasis. Therefore, FMC has been proposed as a relevant model for aggressive human breast cancer. The goals of this study were to develop a nude mouse model of FMC tumor growth and metastasis and to measure the expression of genes responsible for lymphangiogenesis, angiogenesis, tumor progression, and lymph node metastasis in FMC tissues and cell lines. Two primary FMC tissues were injected subcutaneously, and 6 FMC cell lines were injected into 3 sites (subcutaneous, intratibial, and intracardiac) in nude mice. Tumors and metastases were monitored using bioluminescent imaging and characterized by gross necropsy, radiology, and histopathology. Molecular characterization of invasion and metastasis genes in FMC was conducted using quantitative real-time reverse transcription polymerase chain reaction in 6 primary FMC tissues, 2 subcutaneous FMC xenografts, and 6 FMC cell lines. The histologic appearance of the subcutaneous xenografts resembled the primary tumors. No metastasis was evident following subcutaneous injection of tumor tissues and cell lines, whereas lung, brain, liver, kidney, eye, and bone metastases were confirmed following intratibial and intracardiac injection of FMC cell lines. Finally, 15 genes were differentially expressed in the FMC tissues and cell lines. The highly expressed genes in all samples were PDGFA, PDGFB, PDGFC, FGF2, EGFR, ERBB2, ERBB3, VEGFD, VEGFR3, and MYOF. Three genes ( PDGFD, ANGPT2, and VEGFC) were confirmed to be of stromal origin. This investigation demonstrated the usefulness of nude mouse models of experimental FMC and identified molecular targets of FMC progression and metastasis. PMID- 27281015 TI - The Rise of Forensic Pathology in Human Medicine: Lessons for Veterinary Forensic Pathology. AB - The rise of forensic pathology in human medicine has greatly contributed to the administration of justice, public safety and security, and medical knowledge. However, the evolution of human forensic pathology has been challenging. Veterinary forensic pathologists can learn from some of the lessons that have informed the growth and development of human forensic pathology. Three main observations have emerged in the past decade. First, wrongful convictions tell us to use a truth-seeking stance rather than an a priori "think dirty" stance when investigating obscure death. Second, missed homicides and concealed homicides tell us that training and certification are the beginning of reliable forensic pathology. Third, failure of a sustainable institutional arrangement that fosters a combination of service, research, and teaching will lead to stagnation of knowledge. Forensic pathology of humans and animals will flourish, help protect society, and support justice if we embrace a modern biomedical scientific model for our practice. We must build training programs, contribute to the published literature, and forge strong collaborative institutions. PMID- 27281016 TI - Schistosomus Reflexus Syndrome in Olive Ridley Sea Turtles ( Lepidochelys olivacea). AB - The olive ridley sea turtle ( Lepidochelys olivacea), considered the most abundant sea turtle species, is listed as vulnerable on the International Union for Conservation of Nature Red List. The most important nesting areas are located in the Eastern Pacific, and congenital malformations have been previously reported in this species. The present study was conducted in a single population at El Verde beach, one of the most important nesting beaches for the species in the northwestern Mexican Pacific. The study was based on embryos that had been incubated in a controlled environment. Schistosomus reflexus syndrome (SRS) was observed in 124 of 20 257 olive ridley embryos (0.6%), comprising 124 of 400 (31%) cases of congenital malformations over a 7-month period. Affected embryos had malformations of the carapace, bridge, or plastron, resulting in exposure of the abdominal or thoracic viscera, as well as spinal malformation and abnormal positioning of limbs adjacent to the head with subsequent ankylosis. SRS phenotypes (although lethal) varied from mild to severe, although most cases were severe. SRS was mostly associated with congenital malformations in the neck (short neck, 80%), tail (anury, 38%), and flippers (different types of dysmelias, 53%). In most cases of severe SRS, ankyloses were present. Documenting these findings could be important to identify the cause of the developmental defects, and identification of the cause of the defects may be of significance to the population and to our efforts to manage this and other populations at risk. PMID- 27281018 TI - In Memoriam. PMID- 27281017 TI - Decidualization of Endometriosis in Macaques. AB - The decidua is the superficial portion of endometrium that transforms, or decidualizes, under the influence of progesterone to nourish the early embryo during pregnancy. Deciduae outside the uterus are found in nearly 100% of human pregnancies. This condition, known as deciduosis, may mimic malignancy, resulting in additional diagnostic procedures that place the mother, baby, or both at risk. Deciduosis has been described in both Old World and New World nonhuman primates in conjunction with pregnancy and after treatment with exogenous progestins. Here the authors present 6 cases of deciduosis associated with endometriotic lesions in female rhesus and cynomolgus macaques (Macaca mulatta and Macaca fascicularis). Full diagnostic necropsies with histologic analyses were performed on all animals. Deciduae were stained with hematoxylin and eosin and by immunohistochemistry for vimentin, CD10, progesterone receptor, estrogen receptor, desmin, cytokeratin, kermix P8, chorionic gonadotropin, human placental lactogen, and calretinin. The most common clinical signs were abdominal pain (4 of 6) and anorexia (2 of 6). At necropsy, macaque uteri were often enlarged or disfigured (4 of 6) with abundant fibrous adhesions (5 of 6). Affected tissue consisted of epithelial-lined cysts and decidualized stroma with scattered gamma/delta T cells. Decidualized stromal cells were large and polyhedral with abundant cytoplasm and round vesicular nuclei. They stained positive for vimentin, CD10, progesterone, and estrogen. In summary, these cases illustrate deciduosis in 6 nonhuman primates with endometriosis. Understanding decidualization in nonhuman primates will aid in elucidating the pathophysiology of deciduosis during pregnancy or endometriosis and potentially lead to new interventions. PMID- 27281019 TI - Remodeling of B-Cell Subsets in Blood during Pegylated IFNalpha-2a Therapy in Patients with Chronic Hepatitis B Infection. AB - The ultimate goal of pegylated interferon-alfa-2a (Peg-IFN-alpha) therapy in chronic hepatitis B (CHB) infection is HBsAg seroconversion. Even though B cells are major mediators of a positive clinical outcome, their modulation during Peg IFN-alpha therapy has not yet been described. We investigated here the effects of Peg-IFN-alpha on eight circulating B-cell subsets thanks to an original multi gating approach based on CD19, CD27, IgD, CD10, and CD38 markers in patients with CHB treated with nucleos(t)ide analog alone or in combination with Peg-IFN-alpha. These dynamic changes were analyzed during the 48-weeks of Peg-IFN-alpha therapy and up to 2 years after the cessation of treatment. The CD19+CD27 IgD+CD10+CD38high transitional B cells and the CD19+CD27+IgD-CD10-CD38high plasmablasts continuously increased, whereas the CD19+CD27-IgD+CD10-CD38low naive, CD19+CD27+IgD+ natural memory, and CD19+CD27+IgD-CD10-CD38low post germinal center B cells decreased during the course of Peg-IFNalpha treatment. Such modulations correlated with a sustained increase in sCD30 levels and the decrease in plasma HBsAg. However, no seroconversion occurred and all parameters returned to baseline after the stop of the treatment. Peg-IFN-alpha therapy mediates a remodeling of B-cell compartmentalization, without clinical relevance. Our study provides new insights into the immunomodulatory effects of Peg-IFN alpha on circulating B-cells, and questioned the benefit of the add-on Peg-IFN alpha treatment in CHB. PMID- 27281020 TI - Assessing Commitment and Reporting Fidelity to a Text Message-Based Participatory Surveillance in Rural Western Uganda. AB - Syndromic surveillance, the collection of symptom data from individuals prior to or in the absence of diagnosis, is used throughout the developed world to provide rapid indications of outbreaks and unusual patterns of disease. However, the low cost of syndromic surveillance also makes it highly attractive for the developing world. We present a case study of electronic participatory syndromic surveillance, using participant-mobile phones in a rural region of Western Uganda, which has a high infectious disease burden, and frequent local and regional outbreaks. Our platform uses text messages to encode a suite of symptoms, their associated durations, and household disease burden, and we explore the ability of participants to correctly encode their symptoms, with an average of 75.2% of symptom reports correctly formatted between the second and 11th reporting timeslots. Concomitantly we identify divisions between participants able to rapidly adjust to this unusually participatory style of data collection, and those few for whom the study proved more challenging. We then perform analyses of the resulting syndromic time series, examining the clustering of symptoms by time and household to identify patterns such as a tendency towards the within-household sharing of respiratory illness. PMID- 27281022 TI - Formation mechanism of ultra porous framework materials. AB - Understanding the formation mechanism of ultra porous framework materials may lead to insights into strategies for the design and synthesis of novel ultra porous materials or for the increased surface area of known materials. Several potential formation mechanisms have been proposed based on experimental evidence. Here, we assess, via simulation of the network generation process, these mechanisms and have identified key processes by which network interpenetration is minimised and hence surface area is maximised. PMID- 27281021 TI - Role of Brain NUCB2/nesfatin-1 in the Stress-induced Modulation of Gastrointestinal Functions. AB - BACKGROUND: Nucleobindin2 (NUCB2)/nesfatin-1 plays a well-established role in homeostatic functions associated with food intake and stress integration. AIM: This review focusses on NUCB2/nesfatin-1's central effects on gastrointestinal functions and will summarize the effects on food intake, motility and secretion with focus on the upper gastrointestinal tract. RESULTS: We will highlight the stressors that influence brain NUCB2/nesfatin-1 expression and discuss functional implications. In addition to traditional acute psychological and physical stressors such as restraint stress and abdominal surgery we will look at immunological, visceral and metabolic stressors as well as a chronic combination stress model that have been shown to affect NUCB2/nesfatin-1 signaling and describe associated functional consequences. PMID- 27281023 TI - Correction: Interactive Effects of Black-Tailed Prairie Dogs and Cattle on Shrub Encroachment in a Desert Grassland Ecosystem. AB - [This corrects the article DOI: 10.1371/journal.pone.0154748.]. PMID- 27281025 TI - Continuing Education Workshops in Bioinformatics Positively Impact Research and Careers. AB - Bioinformatics.ca has been hosting continuing education programs in introductory and advanced bioinformatics topics in Canada since 1999 and has trained more than 2,000 participants to date. These workshops have been adapted over the years to keep pace with advances in both science and technology as well as the changing landscape in available learning modalities and the bioinformatics training needs of our audience. Post-workshop surveys have been a mandatory component of each workshop and are used to ensure appropriate adjustments are made to workshops to maximize learning. However, neither bioinformatics.ca nor others offering similar training programs have explored the long-term impact of bioinformatics continuing education training. Bioinformatics.ca recently initiated a look back on the impact its workshops have had on the career trajectories, research outcomes, publications, and collaborations of its participants. Using an anonymous online survey, bioinformatics.ca analyzed responses from those surveyed and discovered its workshops have had a positive impact on collaborations, research, publications, and career progression. PMID- 27281024 TI - Transient Receptor Potential Ankyrin 1 Channels Modulate Inflammatory Response in Respiratory Cells from Patients with Cystic Fibrosis. AB - Pseudomonas aeruginosa colonization, prominent inflammation with massive expression of the neutrophil chemokine IL-8, and luminal infiltrates of neutrophils are hallmarks of chronic lung disease in patients with cystic fibrosis (CF). The nociceptive transient receptor potential ankyrin (TRPA) 1 calcium channels have been recently found to be involved in nonneurogenic inflammation. Here, we investigate the role of TRPA1 in CF respiratory inflammatory models in vitro. Expression of TRPA1 was evaluated in CF lung tissue sections and cells by immunohistochemistry and immunofluorescence. Epithelial cell lines (A549, IB3-1, CuFi-1, CFBE41o-) and primary cells from patients with CF were used to: (1) check TRPA1 function modulation, by Fura-2 calcium imaging; (2) down-modulate TRPA1 function and expression, by pharmacological inhibitors (HC-030031 and A-967079) and small interfering RNA silencing; and (3) assess the effect of TRPA1 down-modulation on expression and release of cytokines upon exposure to proinflammatory challenges, by quantitative RT-PCR and 27-protein Bioplex assay. TRPA1 channels are expressed in the CF pseudostratified columnar epithelium facing the bronchial lumina exposed to bacteria, where IL-8 is coexpressed. Inhibition of TRPA1 expression results in a relevant reduction of release of several cytokines, including IL-8 and the proinflammatory cytokines IL 1beta and TNF-alpha, in CF primary bronchial epithelial cells exposed to P. aeruginosa and to the supernatant of mucopurulent material derived from the chronically infected airways of patients with CF. In conclusion, TRPA1 channels are involved in regulating the extent of airway inflammation driven by CF bronchial epithelial cells. PMID- 27281026 TI - Association between High Serum Homocysteine Levels and Biochemical Characteristics in Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Elevated homocysteine levels have been observed in previous studies of PCOS; however, the nature of the associations between high homocysteine levels and the biochemical characteristics of polycystic ovarian syndrome (PCOS)-such as obesity, insulin resistance (IR), and androgen levels-is still uncertain. METHODS: A systematic search was conducted electronically up to December 28, 2015 using specific eligibility criteria. Standardized mean difference (SMD) and the corresponding 95% confidence intervals (95% CIs) were used as a measure of effect size. RESULTS: A total of 34 studies (with 1,718 cases and 1,399 controls) of homocysteine levels in PCOS were pooled in this meta-analysis. Significantly lower homocysteine levels were found in controls than in PCOS patients (SMD = 0.895, 95% CI = 0.643-1.146, P<0.001; I2 = 90.4% and P<0.001 for heterogeneity), regardless of the degree of obesity, IR, or androgen levels. Homocysteine levels in non-IR PCOS patients were significantly lower than those of PCOS patients with IR (SMD = 0.69, 95% CI = 0.37-1.01, P<0.01; I2 = 0% and P = 0.50 for heterogeneity). However, metformin treatment did not appear to cause any significant change in the homocysteine levels of PCOS patients (SMD = -0.17, 95% CI = -1.10-0.75, P = 0.71; I2 = 92% and P<0.01 for heterogeneity). CONCLUSIONS: High homocysteine levels in women with PCOS are not related to degree of obesity, IR, or androgen levels. Metformin treatment cannot decrease the homocysteine levels in PCOS patients. PMID- 27281027 TI - Efficacy and Safety of Plastic Wrap for Prevention of Hypothermia after Birth and during NICU in Preterm Infants: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: This meta-analysis aimed to investigate the efficacy and safety of plastic wrap applied after birth and during NICU in preterm infants for prevention of heat loss in preterm infants. STUDY METHODS: The Medline (1950 to August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7, 2015), CINAHL (1982 to August 2015) and the Embase (1974 to August 2015) databases were searched for randomized controlled trials (RCTs) or quasi-RCTs with main outcomes related to the core temperature (baseline temperature and/or post-stabilization temperature), hypothermia, mortality rate and hyperthermia. RESULT: The included studies were of low to moderate quality. Compared with unwrapped infants, plastic wrap was associated with a significantly higher baseline temperature and post-stabilization temperature both in infants < 28 weeks of gestation (mean difference [MD] = 0.62, 95% CI 0.38 to 0.85; MD = 0.41, 95% CI 0.33 to 0.50, respectively), and in infants between 28 to 34 weeks of gestation (MD = 0.54, 95% CI 0.21 to 0.87; MD = 0.64, 95% CI 0.45 to 0.82, respectively). Use of plastic wrap was associated with lower incidence of hypothermia (relative risk [RR] = 0.70, 95% CI 0.63 to 0.78). However, use of plastic wrap in preterm infants was not associated with decrease in mortality (RR: 0.88, 95% CI 0.70 to 1.12, P = 0.31). Incidence of hyperthermia was significantly higher in the plastic wrap group as compared to that in the control group (RR = 2.55, 95% CI: 1.56 to 4.15, P = 0.0002). Hyperthermia in the plastic wrap group was resolved within one or two hours after unwrapping the babies. CONCLUSION: Plastic wrap can be considered an effective and safe additional intervention to prevent hypothermia in preterm infants. However, its cost effectiveness and long-term effect on mortality needs to be ascertained by conducting well-designed studies with longer follow-up period. PMID- 27281028 TI - Individual and Household Level Risk Factors Associated with Malaria in Nchelenge District, a Region with Perennial Transmission: A Serial Cross-Sectional Study from 2012 to 2015. AB - BACKGROUND: The scale-up of malaria control interventions has resulted in substantial declines in transmission in some but not all regions of sub-Saharan Africa. Understanding factors associated with persistent malaria transmission despite control efforts may guide targeted interventions to high-risk areas and populations. METHODS: Household malaria surveys were conducted in Nchelenge District, Luapula Province, in northern Zambia. Structures that appeared to be households were enumerated from a high-resolution satellite image and randomly sampled for enrollment. Households were enrolled into cross-sectional (single visit) or longitudinal (visits every other month) cohorts but analyses were restricted to cross-sectional visits and the first visit to longitudinal households. During study visits, a questionnaire was administered to adults and caretakers of children and a blood sample was collected for a malaria rapid diagnostic test (RDT) from all household residents. Characteristics associated with RDT positivity were analyzed using multi-level models. RESULTS: A total of 2,486 individuals residing within 742 households were enrolled between April 2012 and July 2015. Over this period, 51% of participants were RDT positive. Forty three percent of all RDT positive individuals were between the ages of 5 and 17 years although this age group comprised only 30% of study participants. In a multivariable model, the odds being RDT positive were highest in 5-17 year olds and did not vary by season. Children 5-17 years of age had 8.83 higher odds of being RDT positive compared with those >18 years of age (95% CI: 6.13, 12.71); there was an interaction between age and report of symptoms, with an almost 50% increased odds of report of symptoms with decreasing age category (OR = 1.49; 95% CI 1.11, 2.00). CONCLUSIONS: Children and adolescents between the ages of 5 and 17 were at the highest risk of malaria infection throughout the year. School based programs may be effective at targeting this high-risk group. PMID- 27281029 TI - Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. AB - The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was delivered at a single timepoint around radiation. Surprisingly, the optimal timing of these therapies varied. Anti-CTLA4 was most effective when given prior to radiation therapy, in part due to regulatory T cell depletion. Administration of anti-OX40 agonist antibody was optimal when delivered one day following radiation during the post-radiation window of increased antigen presentation. Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures. These data demonstrate that the combination of immunotherapy and radiation results in improved therapeutic efficacy, and that the ideal timing of administration with radiation is dependent on the mechanism of action of the immunotherapy utilized. PMID- 27281031 TI - Correction: Viruses Utilize Cellular Cues in Distinct Combination to Undergo Systematic Priming and Uncoating. AB - [This corrects the article DOI: 10.1371/journal.ppat.1005467.]. PMID- 27281032 TI - Forecast Modelling via Variations in Binary Image-Encoded Information Exploited by Deep Learning Neural Networks. AB - Traditional forecasting models fit a function approximation from dependent invariables to independent variables. However, they usually get into trouble when date are presented in various formats, such as text, voice and image. This study proposes a novel image-encoded forecasting method that input and output binary digital two-dimensional (2D) images are transformed from decimal data. Omitting any data analysis or cleansing steps for simplicity, all raw variables were selected and converted to binary digital images as the input of a deep learning model, convolutional neural network (CNN). Using shared weights, pooling and multiple-layer back-propagation techniques, the CNN was adopted to locate the nexus among variations in local binary digital images. Due to the computing capability that was originally developed for binary digital bitmap manipulation, this model has significant potential for forecasting with vast volume of data. The model was validated by a power loads predicting dataset from the Global Energy Forecasting Competition 2012. PMID- 27281030 TI - Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models. AB - The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ 47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders. PMID- 27281033 TI - The Role of Age in Change in Unmet Supportive Care Needs in Hepatocellular Carcinoma Patients During Transition From Hospital to Home. AB - BACKGROUND: Age might affect the change in care needs in patients with hepatocellular carcinoma after treatment during their transition process from hospital to home. However, there have been no studies that focus on this. OBJECTIVE: The aim of this study is to examine changes in unmet supportive care needs in young (<65 years old) and elderly (>=65 years old) groups of patients with hepatocellular carcinoma from before discharge to 2 months after discharge. METHODS: A longitudinal prospective study design was used with recruited participants at a teaching hospital in Taiwan. Data were collected 3 times: within 3 days before discharge and at 1 and 2 months after discharge. A set of questionnaires was used to assess participants' levels of supportive care needs, symptom distress, anxiety, and depression. RESULTS: A total of 104 patients completed the data collection process. Supportive care needs decreased monthly after discharge, with health system and information being the domain with the highest level of unmet needs in the 2 groups. The young group had a higher level of overall unmet needs before discharge, but they had a lower level of overall needs compared with the elderly group after 2 months of discharge. CONCLUSIONS: Age could be a significant potential factor to affect change in unmet needs during transition. IMPLICATIONS FOR PRACTICE: Comprehensive assessment in care needs especially in the health system and information and physical and daily living domains before discharge is recommended to design personalized education programs before discharge. PMID- 27281034 TI - Exploring Chinese Women's Perception of Cervical Cancer Risk as It Impacts Screening Behavior: A Qualitative Study. AB - BACKGROUND: Chinese women rarely undergo regular cervical screening. Women's decisions about cervical screening may be influenced by their perception of the risk of cervical cancer. Therefore, understanding how women perceive the risk of cervical cancer, how personal risk factors are interpreted, and the influence of cultural issues on cervical screening behavior is important. OBJECTIVE: The aim of this study is to understand cervical cancer risk perception and the role of personal risk factors as they influence screening behavior among Chinese women. METHOD: An exploratory qualitative research design was used. We conducted semistructured, in-depth interviews of 27 women in Changsha, a medium-size city in Hunan province, China. RESULTS: Participants identified that cervical cancer had serious consequences, but they distanced themselves psychologically from the disease because they felt that "cervical cancer is a shameful and deadly disease." Although women identified some of the risk factors for the disease, they had little specific knowledge of human papillomavirus infection, its association with cervical cancer, and the importance of cervical screening. CONCLUSION: This study contributes new knowledge to the understanding of cervical screening behavior within a specific social and cultural context. Better efforts should be made to educate Chinese women on the risk of cervical cancer and emphasize that effective cancer treatments are available and that there is a good chance of survival. IMPLICATIONS FOR PRACTICE: Nurses working with Chinese women should ensure that the information they provide is culturally sensitive, particularly by acknowledging the normative beliefs of this population group. PMID- 27281035 TI - Bis-corannulenoanthracene: An Angularly Fused Pentacene as a Precursor for Barrelene-Tethered Receptors for Fullerenes. AB - Bis-corannulenoanthracene (C50H22, 5) was prepared by the Diels-Alder double cycloaddition of isocorannulenofuran with "bis-benzyne", followed by deoxygenation of the adducts. Despite the presence of a pentacene core, 5 is stable enough to be isolated and stored. A cycloaddition reaction of 5 with maleic anhydride produces 10 which exhibits strong affinity toward C60, as evidenced by (1)H NMR titration experiment. Synthesis of 10 demonstrates the synthetic utility of hydrocarbon 5 in the preparation of the barrelene-based molecular clips with two benzocorannulene pincers adorned with polar substituents on their tethers, which will allow for immobilization of the receptors on solid supports. PMID- 27281036 TI - Loss of epithelial FAM20A in mice causes amelogenesis imperfecta, tooth eruption delay and gingival overgrowth. AB - FAM20A has been studied to a very limited extent. Mutations in human FAM20A cause amelogenesis imperfecta, gingival fibromatosis and kidney problems. It would be desirable to systemically analyse the expression of FAM20A in dental tissues and to assess the pathological changes when this molecule is specifically nullified in individual tissues. Recently, we generated mice with a Fam20A-floxed allele containing the beta-galactosidase reporter gene. We analysed FAM20A expression in dental tissues using X-Gal staining, immunohistochemistry and in situ hybridization, which showed that the ameloblasts in the mouse mandibular first molar began to express FAM20A at 1 day after birth, and the reduced enamel epithelium in erupting molars expressed a significant level of FAM20A. By breeding K14-Cre mice with Fam20A(flox/flox) mice, we created K14 Cre;Fam20A(flox/flox) (conditional knock out, cKO) mice, in which Fam20A was inactivated in the epithelium. We analysed the dental tissues of cKO mice using X ray radiography, histology and immunohistochemistry. The molar enamel matrix in cKO mice was much thinner than normal and was often separated from the dentinoenamel junction. The Fam20A-deficient ameloblasts were non-polarized and disorganized and were detached from the enamel matrix. The enamel abnormality in cKO mice was consistent with the diagnosis of amelogenesis imperfecta. The levels of enamelin and matrix metalloproteinase 20 were lower in the ameloblasts and enamel of cKO mice than the normal mice. The cKO mice had remarkable delays in the eruption of molars and hyperplasia of the gingival epithelium. The findings emphasize the essential roles of FAM20A in the development of dental and oral tissues. PMID- 27281037 TI - One-year water-ageing of calcium phosphate composite containing nano-silver and quaternary ammonium to inhibit biofilms. AB - Dental composites are commonly used restorative materials; however, secondary caries due to biofilm acids remains a major problem. The objectives of this study were (1) to develop a composite containing quaternary ammonium dimethacrylate (QADM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP), and (2) to conduct the first investigation of the mechanical properties, biofilm response and acid production vs water-ageing time from 1 day to 12 months. A 4 * 5 design was utilized, with four composites (NACP-QADM composite, NACP-NAg composite, NACP-QADM-NAg composite, and a commercial control composite), and five water-ageing time periods (1 day, and 3, 6, 9, and 12 months). After each water-ageing period, the mechanical properties of the resins were measured in a three-point flexure, and antibacterial properties were tested via a dental plaque biofilm model using human saliva as an inoculum. After 12 months of water-ageing, NACP-QADM-NAg had a flexural strength and elastic modulus matching those of the commercial control (P>0.1). Incorporation of QADM or NAg into the NACP composite greatly reduced biofilm viability, metabolic activity and acid production. A composite containing both QADM and NAg possessed a stronger antibacterial capability than one with QADM or NAg alone (P<0.05). The anti biofilm activity was maintained after 12 months of water-ageing and showed no significant decrease with increasing time (P>0.1). In conclusion, the NACP-QADM NAg composite decreased biofilm viability and lactic acid production, while matching the load-bearing capability of a commercial composite. There was no decrease in its antibacterial properties after 1 year of water-ageing. The durable antibacterial and mechanical properties indicate that NACP-QADM-NAg composites may be useful in dental restorations to combat caries. PMID- 27281038 TI - Heterogeneity of T-Tubules in Pig Hearts. AB - BACKGROUND: T-tubules are invaginations of the sarcolemma that play a key role in excitation-contraction coupling in mammalian cardiac myocytes. Although t-tubules were generally considered to be effectively absent in atrial myocytes, recent studies on atrial cells from larger mammals suggest that t-tubules may be more numerous than previously supposed. However, the degree of heterogeneity between cardiomyocytes in the extent of the t-tubule network remains unclear. The aim of the present study was to investigate the t-tubule network of pig atrial myocytes in comparison with ventricular tissue. METHODS: Cardiac tissue was obtained from young female Landrace White pigs (45-75 kg, 5-6 months old). Cardiomyocytes were isolated by arterial perfusion with a collagenase-containing solution. Ca2+ transients were examined in field-stimulated isolated cells loaded with fluo-4 AM. Membranes of isolated cells were visualized using di-8-ANEPPS. T-tubules were visualized in fixed-frozen tissue sections stained with Alexa-Fluor 488 conjugated WGA. Binary images were obtained by application of a threshold and t tubule density (TTD) calculated. A distance mapping approach was used to calculate half-distance to nearest t-tubule (HDTT). RESULTS & CONCLUSION: The spatio-temporal properties of the Ca2+ transient appeared to be consistent with the absence of functional t-tubules in isolated atrial myocytes. However, t tubules could be identified in a sub-population of atrial cells in frozen sections. While all ventricular myocytes had TTD >3% (mean TTD = 6.94+/-0.395%, n = 24), this was true of just 5/22 atrial cells. Mean atrial TTD (2.35+/-0.457%, n = 22) was lower than ventricular TTD (P<0.0001). TTD correlated with cell-width (r = 0.7756, n = 46, P<0.0001). HDTT was significantly greater in the atrial cells with TTD <=3% (2.29+/-0.16 MUm, n = 17) than in either ventricular cells (1.33+/-0.05 MUm, n = 24, P<0.0001) or in atrial cells with TTD >3% (1.65+/-0.06 MUm, n = 5, P<0.05). These data demonstrate considerable heterogeneity between pig cardiomyocytes in the extent of t-tubule network, which correlated with cell size. PMID- 27281039 TI - Tuning the Surface of Nanoparticles: Impact of Poly(2-ethyl-2-oxazoline) on Protein Adsorption in Serum and Cellular Uptake. AB - Due to the adsorption of biomolecules, the control of the biodistribution of nanoparticles is still one of the major challenges of nanomedicine. Poly(2-ethyl 2-oxazoline) (PEtOx) for surface modification of nanoparticles is applied and both protein adsorption and cellular uptake of PEtOxylated nanoparticles versus nanoparticles coated with poly(ethylene glycol) (PEG) and non-coated positively and negatively charged nanoparticles are compared. Therefore, fluorescent poly(organosiloxane) nanoparticles of 15 nm radius are synthesized, which are used as a scaffold for surface modification in a grafting onto approach. With multi-angle dynamic light scattering, asymmetrical flow field-flow fractionation, gel electrophoresis, and liquid chromatography-mass spectrometry, it is demonstrated that protein adsorption on PEtOxylated nanoparticles is extremely low, similar as on PEGylated nanoparticles. Moreover, quantitative microscopy reveals that PEtOxylation significantly reduces the non-specific cellular uptake, particularly by macrophage-like cells. Collectively, studies demonstrate that PEtOx is a very effective alternative to PEG for stealth modification of the surface of nanoparticles. PMID- 27281041 TI - Why can't we fund supported employment? AB - Work is one of the most valued social rules in modern society, contributing to a person's sense of economic well-being, self-esteem, personal identity, and social status. Conversely, the inability to work or sustain employment due to a psychiatric condition is the primary factor in determining eligibility for disability benefits, such as Social Security Disability Income or Social Security Supplemental Income. Just as work is valued strongly by society, it is also important to people with serious mental illness. In this editorial, we contemplate why we cannot "do the right thing" and fully fund supported employment for persons with serious mental illness. (PsycINFO Database Record PMID- 27281040 TI - Understanding Social Situations (USS): A proof-of-concept social-cognitive intervention targeting theory of mind and attributional bias in individuals with psychosis. AB - OBJECTIVES: In this proof-of-concept trial, we examined the feasibility and preliminary efficacy of Understanding Social Situations (USS), a new social cognitive intervention that targets higher level social-cognitive skills using methods common to neurocognitive remediation, including drill and practice and hierarchically structured training, which may compensate for the negative effects of cognitive impairment on learning. METHOD: Thirty-eight individuals with schizophrenia spectrum disorders completed the same baseline assessment of cognitive and social-cognitive functioning twice over a 1-month period to minimize later practice effects, then received 7-10 sessions of USS training, and then completed the same assessment again at posttreatment. RESULTS: USS training was well tolerated and received high treatment satisfaction ratings. Large improvements on the USS Skills Test, which contained items similar to but not identical to training stimuli, suggest that we were effective in teaching specific training content. Content gains generalized to improvements on some of the social-cognitive tasks, including select measures of attributional bias and theory of mind. Importantly, baseline neurocognition did not impact the amount of learning during USS (as indexed by the USS Skills Test) or the amount of improvement on social-cognitive measures. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: USS shows promise as a treatment for higher level social-cognitive skills. Given the lack of relationship between baseline cognition and treatment effects, it may be particularly appropriate for individuals with lower range cognitive function. (PsycINFO Database Record PMID- 27281042 TI - In-vivo job development training among peer providers of homeless veterans supported employment programs. AB - TOPIC: This column describes a goal-oriented, time-limited in vivo coaching/training approach for skills building among peer veterans vocational rehabilitation specialists of the Homeless Veteran Supported Employment Program (HVSEP). PURPOSE: Planning, implementing, and evaluating the training approach for peer providers was intended, ultimately, to support veterans in their goal of returning to community competitive employment. SOURCES USED: The description draws from the training experience that aimed to improve the ability of peer providers to increase both rates of employment and wages of the homeless veterans using their services. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Training peers using an in vivo training approach provided a unique opportunity for the veterans to improve their job development skills with a focus to support employment outcomes for the service users. Peers who received training also expressed that learning skills through an in vivo training approach was more engaging than typical classroom trainings. (PsycINFO Database Record PMID- 27281043 TI - Conjugation-Driven "Reverse Mars-van Krevelen"-Type Radical Mechanism for Low Temperature C-O Bond Activation. AB - C-O bond activation on monofunctional catalysts (metals, carbides, and oxides) is challenging due to activity constraints imposed by energy scaling relationships. Yet, contrary to predictions, recently discovered multifunctional metal/metal oxide catalysts (e.g., Rh/ReOx, Rh/MoOx, Ir/VOx) demonstrate unusually high C-O scission activity at moderate temperatures. Herein, we use extensive density functional theory calculations, first-principles microkinetic modeling, and electronic structure analysis to elucidate the metal/metal oxide synergy in the Ru/RuO2 catalyst, which enables up to 76% yield of the C-O scission product (2 methyl furan) in catalytic transfer hydrogenolysis of furfural at low temperatures. Our key mechanistic finding is a facile radical-mediated C-O bond activation on RuO2 oxygen vacancies, which directly leads to a weakly bound final product. This is the first time the radical reduction mechanism is reported in heterogeneous catalysis at temperatures <200 degrees C. We attribute the unique catalytic properties to the formation of a conjugation-stabilized furfuryl radical upon C-O bond scission, the strong hydroxyl affinity of oxygen vacancies due to the metallic character of RuO2, and the acid-base heterogeneity of the oxide surface. The conjugation-driven radical-assisted C-O bond scission applies to any catalytic surface that preserves the pi-electron system of the reactant and leads to C-O selectivity enhancement, with notable examples including Cu, H covered Pd, self-assembled monolayers on Pd, and oxygen-covered Mo2C. Furthermore, we reveal the cooperativity of active sites in multifunctional catalysts. The mechanism is fully consistent with kinetic studies and isotopic labeling experiments, and the insights gained might prove useful more broadly in overcoming activity constraints induced by energy scaling relationships. PMID- 27281044 TI - Nanocarbon Paper: Flexible, High Temperature, Planar Lighting with Large Scale Printable Nanocarbon Paper (Adv. Mater. 23/2016). AB - On page 4684, C. Dames, L. Hu and co-workers report highly efficient, broadband lighting from printed hybrid nanocarbon structures with carbon nanotubes and reduced graphene oxides. The fast response and excellent stability of the flexible lighting can find applications in a range of emerging applications where the shape and format, as well as being lightweight, are important. PMID- 27281046 TI - Blue Oleds: High-Efficiency Blue Organic Light-Emitting Diodes Based on Thermally Activated Delayed Fluorescence from Phenoxaphosphine and Phenoxathiin Derivatives (Adv. Mater. 23/2016). AB - High-performance blue thermally activated delayed fluorescence (TADF) emitters containing a phenoxaphosphine oxide or phenoxathiin dioxide acceptor unit coupled with a dimethylacridan donor unit are developed by T. Yasuda and co-workers, as desribed on page 4626. These emitters can allow efficient up-conversion of triplet excitons into singlet excitons, leading to both photoluminescence and internal electroluminescence quantum efficiencies of up to nearly 100%. PMID- 27281047 TI - Li-Ion Battery Cathodes: Enhancing Interfacial Bonding between Anisotropically Oriented Grains Using a Glue-Nanofiller for Advanced Li-Ion Battery Cathode (Adv. Mater. 23/2016). AB - The formation of a spinel Lix CoO2 layer in a Ni-rich secondary particle for lithium-ion batteries is reported by S. K. Kwak, J. Cho, and co-workers on page 4705, who find that the spinel-like Lix CoO2 layer, between layered primary particles, can enhance the mechanical strength of secondary particles by enhancing the interfacial binding energy among the grains. Moreover, the layer can effectively protect the unstable surface of the primary particles and offers a fast electron-ion pathway, resulting in overall enhancements of stability and kinetics in battery performance. PMID- 27281048 TI - Graphene Quantum Dots: Molecularly Designed, Nitrogen-Functionalized Graphene Quantum Dots for Optoelectronic Devices (Adv. Mater. 23/2016). AB - H. Tetsuka and co-workers develop a versatile technique to tune the energy levels and energy gaps of nitrogen-functionalized graphene quantum dots (NGQDs) continuously through molecular structure design, as described on page 4632. The incorporation of layers of NGQDs into the structures markedly improves the performance of optoelectronic devices. PMID- 27281049 TI - Metasurfaces: Continuous-Gradient Plasmonic Nanostructures Fabricated by Evaporation on a Partially Exposed Rotating Substrate (Adv. Mater. 23/2016). AB - A continuous-gradient approach of material evaporation is employed by L. Shao, M. Kall, and co-workers to fabricate nanostructures with varying geometric parameters such as thickness, lateral positioning, and orientation on a single substrate. This method for mask lithography, described on page 4658, allows continuous tuning of the physical properties of a sample. The technique is highly valuable in simplifying the overall optimization process for constructing metasurfaces. PMID- 27281052 TI - An investigation into the concurrent collection of human scent and epithelial skin cells using a non-contact sampling device. AB - In criminal investigations, the collection of human scent often employs a non contact, dynamic airflow device, known as the Scent Transfer Unit 100 (STU-100), to transfer volatile organic compounds (VOCs) from an object/person onto a collection material that is subsequently presented to human scent discriminating canines. Human scent is theorized to be linked to epithelial skin cells that are shed at a relatively constant rate allowing both scent and cellular material to be deposited into the environment and/or onto objects. Simultaneous collection of cellular material, with adequate levels of nuclear deoxyribonucleic acid (nDNA), and human scent using a non-invasive methodology would facilitate criminal investigations. This study evaluated the STU-100 for the concurrent collection of human scent and epithelial skin cells from a porous (paper) and non-porous (stainless steel bar) object that was held for a specified period of time in the dominant hand of twenty subjects (10 females and 10 males). Human scent analysis was performed using headspace static solid-phase microextraction with gas chromatography-mass spectrometry (HS-SPME/GC-MS). A polycarbonate filter was used to trap epithelial skin cells which, upon extraction, were subsequently analyzed, inter-laboratory, using the quantitative polymerase chain reaction (qPCR). The STU-100 proved to be inadequate for collecting the minimum number of epithelial skin cells required to obtain nuclear DNA concentrations above the limit of detection for the qPCR kit. With regard to its use for human scent collection, a reduction in the number and mass of compounds was observed when compared to samples that were directly collected. However, when the indirect collection of human scent from the two different objects was compared, a greater number and mass of compounds was observed from the non-porous object than from the porous object. This outcome suggests that the matrix composition of the scent source could affect the efficacy of the human scent collected when using a non-contact, dynamic airflow sampling device. The findings from this study are of importance because although the STU-100 proved to not be suitable for collecting epithelial skin cells for DNA analysis, its non-contact capability allows for the possibility of other potential forensic evidence, like that of human scent, to be obtained. PMID- 27281051 TI - Seasonal Pacing - Match Importance Affects Activity in Professional Soccer. AB - This research explores the influence of match importance on player activity in professional soccer. Therefore, we used an observational approach and analyzed 1,211 matches of German Bundesliga and 2nd Bundesliga. The importance measurement employed is based on post season consequences of teams involved in a match. This means, if a match result could potentially influence the final rank, and this rank would lead to different consequences for a team, such as qualification for Champions League opposed to qualification for Europe League, then this match is classified as important; otherwise not. Activity was quantified by TOTAL DISTANCE COVERED, SPRINTS, FAST RUNS, DUELS, FOULS and ATTEMPTS. Running parameters were recorded using a semi-automatic optical tracking system, while technical variables were collected by professional data loggers. Based on our importance classification, low important matches occurred at the beginning of round 29. A two-way ANOVA indicates significantly increased FAST RUNS (+4%, d = 0.3), DUELS (+16%, d = 1.0) and FOULS (+36%, d = 1.2) in important matches compared to low important ones. For FAST RUNS and FOULS, this effect only exists in Bundesliga. A comparison of the two leagues show that TOTAL DISTANCE COVERED (+3%, d = 0.9), SPRINTS (+25%, d = 1.4) and FAST RUNS (+15%, d = 1.4) are higher compared to 2nd Bundesliga, whilst FOULS is less in Bundesliga (-7%, d = 0.3). No difference in player activity was found between matches at the beginning of a season (round 1 6) and at the end of a season (round 29-34). We conclude that match importance influences player activity in German professional soccer. The most reasonable explanation is a conscious or unconscious pacing strategy, motivated by preserving abilities or preventing injury. Since this tendency mainly exists in Bundesliga, this may suggest that more skilled players show a higher awareness for the need of pacing. PMID- 27281053 TI - Ultrasound characteristics of bruises and their correlation to cutaneous appearance. AB - OBJECTIVE: The primary objective of this study was to compare the cutaneous size of a bruise on gross exam to the subcutaneous depth and height of the hematoma ascertained by ultrasound. The hypothesis was that there would be little correlation between the area of the bruise on cutaneous exam and the height when measured with ultrasound. METHODS: Adult and pediatric patients with bruising were prospectively identified in the emergency department. Photographs and ultrasound images were collected of the bruises and epidemiologic information collected from the patients. The cutaneous area of the bruise was compared with the sonographic characteristics. RESULTS: The subcutaneous depth and height of the hematomas defined by ultrasound did not correlate with the cutaneous area. CONCLUSIONS: The cutaneous appearance of a bruise gives little indication of the depth and size of the subcutaneous bruise. Ultrasound can add information regarding these parameters. PMID- 27281054 TI - Educational Preparation, Roles, and Competencies to Guide Career Development for Cardiac Rehabilitation Nurses. AB - BACKGROUND: Cardiac rehabilitation is one of the most widely recommended strategies to reduce the burden of cardiovascular disease. The multicomponent nature of cardiac rehabilitation programs requires a multidisciplinary team of healthcare professionals including nurses who are equipped with extensive knowledge and skills. However, there is a lack of a comprehensive, explicit career pathway that contains academic and clinical development to prepare nurses to become cardiac rehabilitation specialists. OBJECTIVE: The aim of this study is to identify the 3 essential components for cardiac rehabilitation professionals: (1) educational preparation, (2) role/responsibility, and (3) competency to inform the framework of career development for cardiac rehabilitation nurses. METHODS: Through scoping review, 4 stages from the methodological framework of scoping review by Arksey and O'Malley (Int J Soc Methodol. 2005;8:19-32) were used. RESULTS: Some attempts have been made in developing frameworks of career development for cardiac rehabilitation professionals with these 3 components through guidelines/standards and core curriculum development worldwide, among which the United States is the only country with a well-established system including guidelines for cardiac rehabilitation/secondary prevention programs, a position statement in terms of competencies, and certification examination for cardiac rehabilitation professionals. Nevertheless, further development and integration of these efforts, specifically for cardiac rehabilitation nurses, are required. CONCLUSIONS: It is vital to raise the awareness of the significant contribution that appropriately educated and trained nurses make in reducing the global burden of cardiovascular disease through cardiac rehabilitation. Therefore, action on establishing a system of comprehensive, clearly defined career development pathway for cardiac rehabilitation nurses worldwide is of immediate priority. PMID- 27281055 TI - Symptoms Suggestive of Acute Coronary Syndrome: When Is Sex Important? AB - BACKGROUND: Studies have identified sex differences in symptoms of acute coronary syndrome (ACS); however, retrospective designs, abstraction of symptoms from medical records, and variations in assessment forms make it difficult to determine the clinical significance of sex differences. OBJECTIVE: The aim of this study is to determine the influence of sex on the occurrence and distress of 13 symptoms for patients presenting to the emergency department for symptoms suggestive of ACS. METHODS: A total of 1064 patients admitted to 5 emergency departments with symptoms triggering a cardiac evaluation were enrolled. Demographic and clinical variables, symptoms, comorbid conditions, and functional status were measured. RESULTS: The sample was predominantly male (n = 664, 62.4%), white (n = 739, 69.5%), and married (n = 497, 46.9%). Women were significantly older than men (61.3 +/- 14.6 vs 59.5 +/- 13.6 years). Most patients were discharged with a non-ACS diagnosis (n = 590, 55.5%). Women with ACS were less likely to report chest pain as their chief complaint and to report more nausea (odds ratio [OR], 1.56; confidence interval [CI], 1.00-2.42), shoulder pain (OR, 1.76; CI, 1.13-2.73), and upper back pain (OR, 2.92; CI, 1.81 4.70). Women with ACS experienced more symptoms (6.1 vs 5.5; P = .026) compared with men. Men without ACS had less symptom distress compared with women. CONCLUSIONS: Women and men evaluated for ACS reported similar rates of chest pain but differed on other classic symptoms. These findings suggest that women and men should be counseled that ACS is not always accompanied by chest pain and multiple symptoms may occur simultaneously. PMID- 27281056 TI - Influence of Socioeconomic Status and Perceived Barriers on Physical Activity Among Taiwanese Middle-Aged and Older Women. AB - BACKGROUND: Physical activity (PA) is associated with cardiovascular health in general populations, particularly in women. Middle-aged and older women are at high risk of less engagement in PA for unknown and complicated reasons. OBJECTIVES: The aim of this study was to investigate whether PA was positively associated with socioeconomic status and psychosocial correlates of PA (self efficacy and perceived benefits) but inversely correlated with perceived barriers in women (age >40 years). METHODS: A cross-sectional survey of 326 community dwelling women was conducted. Data on socioeconomic status, PA, and its psychosocial correlates (ie, perceived benefits/barriers and self-efficacy) were collected using self-report questionnaires. Analyses were performed by multiple linear regressions. RESULTS: Monthly income (beta = .35, P = .015), employment status (beta = .32, P < .001), and perceived barriers to PA (beta = -.19, P = .008) were significantly associated with PA. More highly educated women participated in more (beta = .13, P = .033) vigorous PA, women with fewer perceived barriers participated in more (beta = -.14, P = .047) moderate intensity PA, and employed women participated in more (beta = .35, P < .001) walking. Significantly higher scores of perceived barriers, including "no trainer," "feeling exhausted," "lack of motivation," and "lack of guidance," were identified in women with low PA compared with those with moderate PA. CONCLUSION: Socioeconomic status and perceived barriers are associated with PA and its intensity level. Some specific barriers provide insights into the key factors that contribute to low PA in middle-aged and older women. These findings can be considered in future interventions to design PA promotion programs for this population to protect against cardiovascular diseases. PMID- 27281057 TI - Testing a Model to Reveal the Predictive Mechanism of Care-Seeking Decisions Among Patients With Acute Myocardial Infarction. AB - BACKGROUND: Extensive research has been conducted to examine the factors affecting care-seeking decisions in patients with acute myocardial infarction (AMI). Such a decision-making process is multifactorial, and its underlying mechanism is yet to be determined. OBJECTIVES: Our aim was to test a theoretically integrated model to identify the mechanisms underlying patients' care-seeking decisions in the context of AMI. METHODS: On the basis of both empirical and theoretical evidence, we proposed that patients' care-seeking decisions are driven by 2 sequential perceptual-cognitive processes concerned with illness labeling and interpretation, as well as the contextual influences of perceived barriers to care seeking and cues from others. A sample of 301 patients was recruited to test this model using structural equation modeling. RESULTS: The model testing revealed good fit with the data (chi = 38.48, df = 30, P = .72; root-mean-square error of approximation = 0.03, normed fit index = 0.96, nonnormed fit index = 0.98, and comparative fit index = 0.99) and explained 46% of the variance in AMI care-seeking delay. Successful action relied on whether patients could correctly attribute the symptom experience to AMI, were aware of their own susceptibility to the condition, and had a good understanding of how the disease manifested itself. Lowering perceived barriers and positive cues from others in advising care seeking played favorable roles to promote care-seeking behaviors. CONCLUSIONS: This integrative theoretical model is shown to be valid in explaining care-seeking delay among AMI patients and can guide the development of interventions to promote appropriate care-seeking behaviors among high-risk individuals. PMID- 27281058 TI - Electronic Cigarette Use Among Working Adults - United States, 2014. AB - Electronic cigarettes (e-cigarettes) are battery-powered devices that deliver a heated aerosol, which typically contains nicotine, flavorings, and other additives, to the user. The e-cigarette marketplace is rapidly evolving, but the long-term health effects of these products are not known. Carcinogens and toxins such as diacetyl, acetaldehyde, and other harmful chemicals have been documented in the aerosol from some e-cigarettes (1-3). On May 5, 2016, the Food and Drug Administration (FDA) finalized a rule extending its authority to all tobacco products, including e-cigarettes.* The prevalence of e-cigarette use among U.S. adults has increased in recent years, particularly among current and former conventional cigarette smokers (4); in 2014, 3.7% of all U.S. adults, including 15.9% of current cigarette smokers, and 22.0% of former cigarette smokers, used e cigarettes every day or some days (5). The extent of current e-cigarette use among U.S. working adults has not been assessed. Therefore, CDC analyzed 2014 National Health Interview Survey (NHIS) data for adults aged >=18 years who were working during the week before the interview, to provide national estimates of current e-cigarette use among U.S. working adults by industry and occupation. Among the estimated 146 million working adults, 3.8% (5.5 million) were current (every day or some days) e-cigarette users; the highest prevalences were among males, non-Hispanic whites, persons aged 18-24 years, persons with annual household income <$35,000, persons with no health insurance, cigarette smokers, other combustible tobacco users, and smokeless tobacco users. By industry and occupation, workers in the accommodation and food services industry and in the food preparation and serving-related occupations had the highest prevalence of current e-cigarette use. Higher prevalences of e-cigarette use among specific groups and the effect of e-cigarette use on patterns of conventional tobacco use underscore the importance of continued surveillance of e-cigarette use among U.S. working adults to inform public health policy, planning, and practice. PMID- 27281059 TI - Polymorphisms in the CD14 and TLR4 genes independently predict CD4+ T-cell recovery in HIV-infected individuals on antiretroviral therapy. AB - BACKGROUND: Chronic HIV infection leads to marked depletion of CD4 T cells in the gastrointestinal tract and increased microbial translocation measured by an increase in circulating lipopolysaccharide (LPS) levels. Here, we hypothesized that single-nucleotide polymorphisms (SNPs) in genes encoding the Toll-like receptor 4 (TLR4) and CD14, the principal receptors for LPS, were associated with CD4 T-cell recovery postantiretroviral therapy (ART). METHODS: Prospective study of predominantly white HIV-infected participants receiving suppressive ART for at least 12 months. We analysed the CD14 SNPs C-260T and the TLR4 SNPs A+896G, C+1196T. We also determined the levels of LPS and soluble CD14 in plasma samples collected pre-ART and post-ART initiation. CD4 T-cell recovery was assessed by linear mixed models. RESULTS: Following ART, individuals with a TT genotype compared with a CT or CC genotype for CD14 C-260T SNP showed higher levels of soluble CD14 (P = 0.008 and 0.003, respectively). The CC genotype for the CD14 C 260T SNP, compared with CT or TT, and the TLR4 SNP (AC/GT), compared with the homozygous genotype (AA/CC), were both independently associated with enhanced long-term CD4 T-cell recovery (>3 months; P < 0.001). CONCLUSION: Polymorphisms in CD14 and TLR4 are independently associated with long-term CD4 T-cell recovery in HIV-infected individuals post-ART. PMID- 27281060 TI - Dysfunctions in the migratory phenotype and properties of circulating immature transitional B cells during HIV-1 infection. AB - OBJECTIVE: The frequency of immature transitional B cells is increased in blood of HIV-1-infected individuals. We investigated whether HIV-1 infection affects expression and function of chemokine receptors important for egress of immature transitional B cells from bone marrow and migration to lymphoid organs. DESIGN: This is a cross-sectional study analysing the migratory phenotype and function of immature transitional B cells in HIV-1-infected individuals, in relation to antiretroviral treatment and age. METHODS: Frequency of blood immature transitional B cells and their phenotypic characteristics, including chemokine receptors and a maturation marker, were determined by immunostainings. Migratory capacities were studied in a migration assay. RESULTS: The increased frequency of immature transitional B cells in untreated HIV-1 infection was normalized in patients receiving antiretroviral treatment; in our cohorts, age did not have an impact on the frequency of circulating immature transitional B cells. Immature transitional B cells from nontreated patients expressed low levels of CD21 molecule. We found an elevated frequency of CXCR3 and CXCR4 expressing immature transitional B cells in treated and nontreated patients. CXCR4 receptor was unresponsive to CXCL12 ligand in in-vitro migration and internalization assays. In addition, CXCR5 expression was downregulated on immature transitional B cells from infected patients, and these cells migrated poorly in response to CXCR5 ligand. CONCLUSION: Circulating immature transitional B cells from HIV-1-infected patients are not fully mature, probably due to premature egress from bone marrow; these cells showed a phenotype which could impair entry into secondary lymphoid organs. Changes in migratory capacity of immature transitional B cells may affect B-cell maturation during HIV-1 infection. PMID- 27281062 TI - NMR Study on Ion Dynamics and Phase Behavior of a Piperidinium-Based Room Temperature Ionic Liquid: 1-Butyl-1-methylpiperidinium Bis(fluorosulfonyl)amide. AB - By use of pulse NMR methods, the temperature dependences of the longitudinal and transverse relaxation times for (1)H and (19)F were measured for the three phases of 1-butyl-1-methylpiperidinium bis(fluorosulfonyl)amide ([Pip1,4][FSA]), i.e., liquid or supercooled liquid, Cryst-alpha, and Cryst-beta, to investigate the ion dynamics and phase behavior related to the dynamics. Since the cations and anions in the room-temperature ionic liquid have (1)H and (19)F nuclei, respectively, the dynamics of the [Pip1,4] cation and [FSA] anion can be independently observed and the relation between them can be evaluated. The relevant local motions of the ions are fluctuational motion around the chair form of the piperidinium ring, libration or rotation of the alkyl groups, and libration or rotation of the SO2F groups around the N-S axes. Each phase preferentially exhibits these motions. In the Cryst-beta phase, it is thought that O atoms in the SO2F groups form strong hydrogen bonds with the H atoms in the piperidinium ring. As a result, the motions of the SO2F groups and the piperidinium ring are restricted. In the liquid or supercooled liquid states and Cryst-alpha phase, the motion of the anion is more significant than that of the cation and the former works as a trigger for phase changes. Particularly, the motion of the SO2F groups in the Cryst-alpha phase becomes very significant with rising temperature and is directly related to the melting phase transition. PMID- 27281061 TI - Differential CD4+ cell count increase and CD4+ : CD8+ ratio normalization with maraviroc compared with tenofovir. AB - OBJECTIVE: Studies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence, it remains unclear whether MVC has unique immunologic effects in comparison with other antiretroviral drugs. We sought to determine whether MVC has differential effects compared with tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy. DESIGN: Prospective study in AIDS Clinical Trials Group A5303, a double-blind, placebo-controlled trial (N = 262) of MVC vs. TDF, each combined with boosted darunavir and emtricitabine. METHODS: A total of 31 cellular and soluble biomarkers were assayed at weeks 0 and 48. Polychromatic flow cytometry was performed on cryopreserved peripheral blood mononuclear cells. Soluble markers were assayed in plasma using ELISA kits. Analyses were as treated. RESULTS: Analyses included 230 participants (119 in MVC arm and 111 in TDF arm). Over 48 weeks of treatment, no significant differences were detected in declines in markers of inflammation and activation with MVC vs. TDF. A greater CD4 T-cell count increase (median +234 vs. +188 cells/MUl, P = 0.036), a smaller CD8 T-cell count decrease (-6 vs. -109 cells/MUl, P = 0.008), and a smaller CD4 : CD8 ratio increase (0.26 vs. 0.39, P = 0.003) occurred with MVC. Among participants with a baseline CD4 : CD8 ratio less than 1, a smaller proportion of MVC group normalized to a ratio greater than 1 at week 48 (15 and 36%, P < 0.001). CONCLUSION: MVC resulted in less improvement in the CD4 : CD8 ratio driven by greater increase in CD4 cell count but smaller decline in CD8 cell count. Changes in soluble or cellular biomarkers of inflammation and immune activation were not different between MVC and TDF. PMID- 27281063 TI - ACA-Pro: calibration protocol for quantitative diffuse reflectance spectroscopy. Validation on contact and noncontact probe- and CCD-based systems. AB - We have developed an adaptive calibration algorithm and protocol (ACA-Pro) that corrects from the instrumental response of various spatially resolved diffuse reflectance spectroscopy (DRSsr) systems to enable the quantification of absorption and scattering properties based on a Monte Carlo-based look-up-table approach. The protocol involves the use of a calibration reference base built with measurements of a range of different diffusive intralipid phantoms. Moreover, an advanced strategy was established to take into account the experimental variations with an additional measurement of a common solid material, allowing the use of a single calibration reference base for all experiments. The ACA-Pro is validated in contact and noncontact probe-based DRSsr systems. Furthermore, the first results of a setup replacing the probe with a CCD detector are shown to confirm the robustness of the approach. PMID- 27281064 TI - Superior performance with sCMOS over EMCCD in super-resolution optical fluctuation imaging. AB - Super-resolution optical fluctuation imaging (SOFI) is a fast and low-cost live cell optical nanoscopy for extracting subdiffraction information from the statistics of fluorescence intensity fluctuation. As SOFI is based on the fluctuation statistics, rather than the detection of single molecules, it poses unique requirements for imaging detectors, which still lack a systematic evaluation. Here, we analyze the influences of pixel sizes, frame rates, noise levels, and different gains in SOFI with simulations and experimental tests. Our analysis shows that the smaller pixel size and faster readout speed of scientific grade complementary metal oxide semiconductor (sCMOS) enables SOFI to achieve high spatiotemporal resolution with a large field-of-view, which is especially beneficial for live-cell super-resolution imaging. Overall, as the performance of SOFI is relatively insensitive to the signal-to-noise ratio (SNR), the gain in pixel size and readout speed exceeds the loss in SNR, indicating sCMOS is superior to electron multiplying charge coupled device in context to SOFI in many cases. Super-resolution imaging of cellular microtubule structures with high order SOFI is experimentally demonstrated at large field-of-view, taking advantage of the large pixel number and fast frame rate of sCMOS cameras. PMID- 27281065 TI - A Response Surface Model Exploration of Dosing Strategies in Gastrointestinal Endoscopies Using Midazolam and Opioids. AB - Classical midazolam-opioid combination for gastrointestinal endoscopy sedation has been adopted for decades. Dosing regimens have been studied but most require fixed dosing intervals. We intend to use a sophisticated pharmacodynamic tool, response surface model (RSM), to simulate sedation using different regimens. RSM can predict patient's response during different phases of the examination and predict patient's wake-up time with precision and without the need for fixed dosing intervals. We believe it will aid physicians in guiding their dosing strategy and timing.The study is divided into 2 parts. The first part is the full Greco RSMs development for 3 distinct phases: esophagogastroduodenoscopy (EGD), colonoscopy, and intersession (the time lapse between procedures). Observer's Assessment of Alertness Score (OAA/S) is used to assess patient response. The second part simulates 6 regimens with different characteristics using the RSMs: midazolam only, balanced midazolam and opioids, high-dose opioids and midazolam, low-dose midazolam with high-dose opioids, high-dose midazolam and low-dose opioids, and finally midazolam with continuous opioid infusion. Loss of response at 95% probability for adequate anesthesia during examination and return of consciousness at 50% probability during intersession was selected for simulation purposes.The average age of the patient population is 49.3 years. Mean BMI is 21.9 +/- 2.3 kg/m. About 56.7% were females and none received prior abdominal surgery. The cecal intubation rate was 100%. Only 1 patient (3%) developed temporary hypoxemia, which was promptly managed with simple measures. The RSMs for each phase showed significant synergy between midazolam and alfentanil. The balanced midazolam and alfentanil combination provided adequate anesthesia and most rapid return of consciousness. The awakening time from the final drug bolus was 7.4 minutes during EGD and colonoscopy stimulation, and 9.1 minutes during EGD simulation.Simulation of regimens with different characteristics gives insights on dosing strategies. A balanced midazolam-alfentanil regimen is adequate in providing good anesthetic depth and most rapid return of consciousness. We believe with the aid of our RSM, clinicians can perform sedation with more flexibility and precision. PMID- 27281066 TI - Efficacy of Anti-TNFalpha in Severe and Refractory Neuro-Behcet Disease: An Observational Study. AB - To report the safety and efficacy of anti-tumor necrosis factor alpha (TNFalpha) therapy in severe and refractory neuro-Behcet disease (NBD) patients.Observational, multicenter study including 17 BD patients (70.6% of male, with a median age of 39.3 [24-60] years), with symptomatic parenchymal NBD, refractory to previous immunosuppressant and treated with anti-TNFalpha (infliximab 5 mg/kg [n = 13] or adalimumab [n = 4]). Complete remission was defined by the disappearance of all neurological symptoms and by the improvement of radiological abnormalities at 12 months.Overall improvement following anti-TNF was evidenced in 16/17 (94.1%) patients including 6 (35.3%) complete response and 10 (58.8%) partial response. The median time to achieve remission was 3 months (1 6). The median Rankin score was 2 (1-4) at the initiation of anti-TNFalpha versus 1 (0-4) at the time of remission (P = 0.01). Corticosteroids have been stopped in 4 (23.5%) patients, and reduced by more than 50% as compared with the dosage at baseline in 10 (58.8%) patients. Side effects occurred in 23.5% of patients and required treatment discontinuation in 17% of cases.TNF blockade represents an effective therapeutic approach for patients with severe and refractory NBD, a difficult to treat population. PMID- 27281067 TI - Laminoplasty versus laminectomy and fusion for multilevel cervical compressive myelopathy: A meta-analysis. AB - This is a meta-analysis to compare the results between laminoplasty and laminectomy followed by fusion for the patients with multilevel cervical compressive myelopathy. An extensive search of literature was performed in MEDLINE, Embase, the Cochrane library, CNKI, and WANFANG. The following outcome measures were extracted: the Japanese Orthopaedic Association (JOA) scores, cervical curvature index (CCI), visual analog scale (VAS), cervical lordosis (C2 7), complications, blood loss, and operation time. Data analysis was conducted with RevMan 5.3 and STATA 12.0. A total of 23 studies comprising 774 and 743 patients treated with laminoplasty and laminectomy followed by fusion, respectively, were included in the final analysis. The pooled analysis showed that there was no significant difference in preoperative JOA scores [P = 0.89], postoperative JOA scores [P = 0.13], JOA scores improvement rate [P = 0.27], preoperative CCI [P = 0.15], postoperative CCI [P = 0.14], preoperative VAS [P = 0.41], postoperative VAS [P = 0.52], preoperative cervical lordosis (C2-7) [P = 0.46], postoperative cervical lordosis (C2-7) [P = 0.67], total complications [P = 0.07], axial pain [P = 0.94], and blood loss [P = 0.51]. However, there were significant difference in operation time (WMD = -19.57 [-32.11, -7.02], P = 0.002) and C5 palsy (OR = 0.26 [0.15, 0.44], P < 0.001). As compared with laminectomy followed by fusion, expansive laminoplasty showed no significant differences in JOA scores, CCI, ROM, VAS, cervical lordosis (C2-7), axial pain, total complications, and blood loss, but shorter operation time and fewer C5 palsy. PMID- 27281068 TI - HER-2 expression in biopsy and surgical specimen on prognosis of osteosarcoma: A systematic review and meta-analysis of 16 studies. AB - Numerous original clinical studies have attempted to investigate the prognostic value of HER-2 overexpression in osteosarcoma, but the results of these studies are not consistent. This meta-analysis and systematic review was performed to further assess the correlation between HER-2 expression and prognosis in patients with osteosarcoma. A detailed search of relevant publications was conducted using 7 electronic databases: PubMed, Embase, the Cochrane library, the Wanfang database, the China National Knowledge Internet (CNKI) database, the Chinese VIP database, and the Chinese Biological Medical (CBM) Database for publications through August 1, 2015, using the following keywords (HER-2 OR ErbB-2 OR C-erbB-2 OR neu) AND (osteosarcoma OR osteogenic tumor). The bibliographies of potentially relevant articles and identified articles were then searched by hand. Eligible studies were those that enrolled participants with osteosarcoma and provided survival outcome in HER-2 positive and negative groups. The hazard ratio (HR) and 95% confidence interval (CI) for each individual study was calculated and pooled to obtain integrated estimates, using random effects modeling. Sixteen studies involving 934 participants with osteosarcoma met our inclusion criteria. HER-2 overexpression was documented in 42.2% of patients with osteosarcoma. Compared with patients without HER-2 overexpression, those overexpressing HER-2 had decreased overall survival (HR = 2.03, 95% CI: 1.36-3.03, P < 0.001). Statistical associations between HER-2 overexpression and unfavorable overall survival (OS) were observed for both biopsy and surgical removal specimens (HR = 2.07, 95%CI: 1.16-3.72, P = 0.014; and HR = 2.02, 95%CI: 1.10-3.71, P = 0.024). Results for disease-free survival (DFS) were similar. Overexpression of HER-2 is significantly associated with poor outcome for patients with osteosarcoma and should be assessed at diagnosis and after surgery as a prognostic factor. However, larger-scale multicenter clinical studies are needed to further support these findings. PMID- 27281069 TI - Hypersensitivity to fluoroquinolones: The expression of basophil activation markers depends on the clinical entity and the culprit fluoroquinolone. AB - Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity-specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = -0.446; P < 0.001 for CD63 and Spearman r = -0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers. PMID- 27281070 TI - Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation. AB - Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child Turcotte-Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients' median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients. However, the occurrence of HCV reactivation and CMV infection in LT patients should be monitored after rATG treatment in these patients. PMID- 27281071 TI - Dysfunctional phenotypes of CD4+ and CD8+ T cells are comparable in patients initiating ART during early or chronic HIV-1 infection. AB - Early initiation of antiretroviral therapy (ART) is becoming a common clinical practice according to current guidelines recommending treatment to all HIV-1 infected patients. However, it is not known whether ART initiated during the early phase of infection prevents the establishment of abnormal phenotypic features previously reported in CD4+ and CD8+T cells during chronic HIV-1 infection. In this cross-sectional study, blood specimens were obtained from 17 HIV-1-infected patients who began ART treatment shortly after infection (early ART [EA]), 17 age-matched HIV-1-infected patients who started ART during chronic phase of infection (late ART [LA]), and 25 age-matched non-HIV-1-infected controls. At collection of specimens, patients in EA and LA groups had received ART for comparable periods of time. Total HIV-1 DNA was measured in white blood cells by quantitative PCR. The concentration of 9 inflammatory parameters and 1 marker of fibrosis, including sCD14 and beta-2 microglobulin, was measured in plasma. Furthermore, expression of markers of abnormal immune activation (human leukocyte antigen - antigen D related [HLA-DR] and CD38), exhaustion (programmed death 1, CD28, CD57) and terminal differentiation (CD127) was measured on CD4+ and CD8+T cells. T-cell proliferation was measured through Ki67 expression. The copies of total HIV-1 DNA in blood were significantly lower (P = 0.009) in EA compared with that in LA group. Only the expression of HLA-DR on naive CD4+ T cells distinguished EA from LA, whereas expression of 3 surface markers distinguished T-cell populations of HIV-1-infected patients from controls. These included HLA-DR distinguishing CD4+ T cells from EA compared with controls, and also CD38 and CD127 on CD4+ and CD8+ T cells, respectively, distinguishing both groups of patients from controls. The sCD14 levels were significantly higher in EA patients, and beta-2 microglobulin levels were higher in LA group compared with that in controls. Our results demonstrate an equivalent abnormal expression of activation (HLA-DR and CD38 on CD4+ T cells) and terminal differentiation (CD127 on CD8+ T cells) markers in T cells from both EA and LA patients. The size of total HIV-1 DNA copies in blood of EA was lower compared with LA patients. These findings suggest that some abnormalities taking place in the T-cell compartment during primary HIV-1 infection may not be corrected by early ART. PMID- 27281072 TI - High Serum Irisin Level as an Independent Predictor of Diabetes Mellitus: A Longitudinal Population-Based Study. AB - Irisin, a novel exercise-induced myokine, has been suggested to regulate energy homeostasis and insulin sensitivity. However, it remains unclear whether circulating irisin plays a role in the development of DM in human. We investigated the possible association between circulating irisin levels and incident DM in a 2.6-year longitudinal study of a population-based cohort comprised of rural Korean subjects.We conducted a longitudinal study within the Korean Genome and Epidemiology Study on Atherosclerosis Risk of Rural Areas in the Korean General Population (KoGES-ARIRANG) study from November 2005 to January 2008. Cases (n=85) were patients with incident DM during the follow-up period and controls (n = 85) were matched to incident DM cases based on sex and age at baseline. The relative risk of serum irisin/adiponectin level for incident DM was analyzed using conditional logistic regression analysis.Baseline irisin_ENREF_1 levels were significantly higher in subjects who developed DM than in subjects who did not. The serum irisin level was positively associated with glycated hemoglobin (HbA1c) and postprandial glucose. Irisin was negatively associated with adiponectin (R = -0.189, P = 0.014). After adjustment for potential confounders, including body mass index, the odds ratios [95% confidence intervals] for incident DM increased in a graded manner as the serum irisin level increased (Quartile 1 vs Quartile 2 vs Quartile 3 vs Quartile 4 = 1 vs 0.80 [0.28 2.35] vs 3.33 [1.11-10.00] vs 4.10 [1.35-12.44], respectively), whereas the odds ratios for incident DM decreased in a graded manner as the serum adiponectin level increased.High serum irisin was independently associated with the development of DM, indicating that irisin may be a useful predictor of DM in Korean adults. PMID- 27281073 TI - Five-Year Long-Term Prognosis of Epileptic Children After Hemispheric Surgery: A Systematic Review and Meta-analysis. AB - To estimate children's long-term seizure outcomes after hemispheric surgery and the associated predictors.A systematic review of 4 databases and a meta-analysis were performed from January 1, 1995 to August 31, 2015. The databases included PubMed, Embase, Science Direct, and Web of Science; patients were classified into the Engel Class I group and the Engel Class II to IV group, according to their seizure outcomes. Nine potential predictors were then stratified across the groups and estimated using the Wilcoxon rank-sum test for continuous variables and the Chi-squared test for categorical variables.The search yielded 15 retrospective studies, with a total sample size of 380. Five years after surgery, 268 (0.71, 95% confidence interval [CI]: 0.64-0.78) children were seizure free; the seizure onset age in the Engel Class I group was significantly higher than that of the Engel Class II to IV group (standardized mean difference [SMD] = 0.26, 95% CI: 0.03-0.49, P = 0.028); specifically, when predicting the positive long-term outcomes, the odds ratio for late onset age (>=3.6 months, median value of the Engel Class II-IV group) versus early onset age was 2.65 (95% CI: 1.454 4.836, z = 3.18, P = 0.001). The abnormal magnetic resonance imaging (MRI) findings were more predictive for positive seizure outcomes than the normal findings (odds ratio [OR] = 4.60, 95% CI: 1.27-16.62, P = 0.02).Following hemispheric surgery, the long-term prognosis of children with epilepsy was good. Late seizure onset (age >= 3.6 months) and abnormal MRI findings were positive predictors for long-term seizure control in children. PMID- 27281074 TI - Use of Traditional and Complementary Medicine as Self-Care Strategies in Community Health Centers: Cross-Sectional Study in Urban Pearl River Delta Region of China. AB - In China, Community Health Centers (CHCs) are major providers of primary care services, but their potential in empowering patients' self-management capacity has not been assessed. This study aims to describe self-care practice patterns amongst CHC attendees in urban China.In this cross-sectional quantitative study, 3360 CHC patients from 6 cities within the Pearl Delta Region were sampled using multistage cluster sampling.Thirty-seven per cent had used with over-the-counter Chinese herbal medicines (OTC CHMs) in the past year and majority of respondents found OTC CHMs effective. OTC CHMs were more popular amongst those who needed to pay out of pocket for CHC services. Less than 10% used vitamins and minerals, and those with a lower socioeconomic background have a higher propensity to consume. Although doubts on their usefulness are expressed, their use by the vulnerable population may reflect barriers to access to conventional health care, cultural affinity, or a defense against negative consequences of illnesses. About 25% performed physical exercise, but the prevalence is lower amongst women and older people. Taiji seems to be an alternative for these populations with promising effectiveness, but overall only 6% of CHC attendees participated.These results suggest that CHCs should start initiatives in fostering appropriate use of OTC CHM, vitamins, and minerals. Engaging community pharmacists in guiding safe and effective use of OTC CHM amongst the uninsured is essential given their low accessibility to CHC services. Prescription of Taiji instead of physical exercises to women and older people could be more culturally appropriate, and the possibility of including this as part of the CHC services worth further exploration. PMID- 27281075 TI - Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis: A Systematic Review and Meta-Analysis. AB - Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC.A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome.Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6-39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events.FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT. PMID- 27281076 TI - Multiorgan resection with inferior vena cava reconstruction for hepatic alveolar echinococcosis: A case report and literature review. AB - Alveolar echinococcosis (AE) is a life-threatening parasitic disease characterized by its tumor-like growth. Radical operation is deemed the curable method for AE treatment if R0-resection is achievable. We present a 26-year-old AE patient with AE lesions invading the right lobe of the liver, the inferior vena cava, inferior lobe of right lung, the right hemidiaphragm, and the right kidney. On the basis of precise preoperative and intraoperative evaluations, a radical surgery that removed the huge lesion en bloc was performed successfully with skillful surgical techniques. This patient had an uneventful postoperative recovery and a good prognosis. Multiorgan resection is justified and unavoidable in selected patients when AE lesions invade different organs and the main vascular structures. PMID- 27281077 TI - The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease. AB - Genetic variants in IL12B, encoding the p40 subunit common in interleukin-12 (IL 12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD.A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behcet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay.The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all P <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (P <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (P = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (P = 0.002) and intestinal BD (P = 0.001) but not that of CD.Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients. PMID- 27281078 TI - Up-regulation of Plasma Hexosylceramide (d18: 1/18: 1) Contributes to Genotype 2 Virus Replication in Chronic Hepatitis C: A 20-Year Cohort Study. AB - The aim of the present study was to explore the relationship between plasma sphingolipids and hepatitis C virus (HCV) replication in chronic hepatitis C (CHC) patients.A cohort of 120 treatment-naive CHC patients was included. Liver biopsies and the Scheuer scoring system were used to assess hepatic inflammatory activity. Blood biochemical indicators, HCV-RNA load, and immunological markers were also measured. Forty-four plasma sphingolipids were identified and quantified using high-performance liquid chromatography-tandem mass spectrometry.The hexosylceramide (HexCer) (d18:1/18:1) level was significantly different between patients with a low HCV load (<10 IU/mL) and a high HCV load (>=10 IU/mL), and it was positively correlated with the HCV-RNA load (r = 0.337, P = 0.001) in CHC patients. Additionally, the plasma HexCer (d18:1/18:1) level (odds ratio 1.302, 95% confidence interval 1.129-1.502) was an independent factor for a high HCV-RNA load. For patients with hepatic inflammation grade <=2 or HCV genotype 2, HexCer (d18:1/18:1) was independently related to a high HCV-RNA load.Plasma HexCer (d18:1/18:1) might be involved in the high viral replication level in chronic HCV infection, especially for CHC patients with genotype 2. PMID- 27281079 TI - Diagnosis and rehabilitation of deep wound infection and internal fixation rejection in elbow: A case report. AB - This study aims at diagnosis and rehabilitation of a rare case of deep wound infection and internal fixation rejection in elbow. The patient sustained a distal fracture in the humerus 1 year ago, which was internal fixed. The wound always effused and the elbow had pain and swelling; joint motion was limited. Blood sedimentation rate and C reactive protein level increased, bacterial culture suggested deep wound infection, and ultrasound indicated inflammation. The main diagnoses were deep wound infection and internal fixation rejection. Therapeutics interventions were antibiotic agents, physical therapy, operative debridement, incision, drainage, and exercise and physical therapy. One year later, the internal fixation was taken out. His elbow was fully mobilized and the fracture healed. He got back to his former job. When encountered deep wound infection again and again after internal fixation, rejection should be considered. Except for anti-infection treatment, rehabilitation cannot be neglected, or the healing process may be delayed. PMID- 27281080 TI - The association between normal-range admission potassium levels in Israeli patients with acute coronary syndrome and early and late outcomes. AB - Abnormal serum potassium levels are associated with an increased risk of ventricular arrhythmias and mortality in patients with acute myocardial infarction (AMI). The aim of the present study was to evaluate whether different levels of serum potassium, within the normal range, are associated with worse outcomes. The present study comprised 1277 patients with AMI and normal-range admission potassium levels (3.5-5.2 mEq/L), who were enrolled and prospectively followed up in the Acute Coronary Syndrome Israeli Survey between 2010 and 2013. Patients were divided into 4 quartiles based on admission potassium levels; "normal-low" (K >= 3.5 and K <= 3.9), "normal-moderate" (K > 3.9 and K <= 4.18), "normal-high" (K > 4.18 and K <= 4.45), and "normal-very high" (K > 4.45 and K <= 5.2). We analyzed the association between admission serum potassium levels and 7 days in-hospital complication rates, and 30-day and 1-year all-cause mortality rates. Patients with "normal-very high" potassium displayed increased frequency of baseline clinical risk factors and experienced a higher rate of acute kidney injury during hospitalization compared with the "normal-low" group (7.7% vs 2.4%; P = 0.002). However, the rate of in-hospital ventricular arrhythmias was similar across the range of admission potassium levels (overall P = 0.26), Multivariate analysis showed that compared with "low-normal" potassium values, patients with "normal-very high" potassium levels experienced increased risk for 30-days (adjusted hazard ratio 2.88, 95% confidence interval 1.05-7.87, P = 0.039) and 1 year all-cause mortality (adjusted hazard ratio 1.98, 95% confidence interval 1.05-3.75, P = 0.034). In patients admitted with AMI, admission serum potassium levels of 4.45 to 5.2 mEq/L are not associated with in-hospital ventricular arrhythmias, but are associated with increased short and long-term mortality. PMID- 27281081 TI - National trends in off-label use of atypical antipsychotics in children and adolescents in the United States. AB - The objectives of the study were as follows: to examine the national trend of pediatric atypical antipsychotic (AAP) use in the United States; to identify primary mental disorders associated with AAPs; to estimate the strength of independent associations between patient/provider characteristics and AAP use. Data are from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. First, average AAP prescription rates among 4 and 18-year-old patients between 1993 and 2010 were estimated. Second, data from 2007 to 2010 were combined and analyzed to identify primary mental disorders related to AAP prescription. Third, a multivariate logistic regression model was developed having the presence of AAP prescription as the dependent variable and patient/provider characteristics as explanatory variables. Adjusted odds ratios (AORs) with associated 95% confidence intervals (CIs) were estimated. Outpatient visits including an AAP prescription among 4 to 18-year-old patients significantly increased between 1993 and 2010 in the United States, and over 65% of those visits did not have diagnoses for US Food and Drug Administration approved AAP indications. During 2007 to 2010, the most common mental disorder was attention-deficit hyperactivity disorder, accounting for 24% of total pediatric AAP visits. Among visits with attention-deficit hyperactivity disorder diagnosis, those with Medicaid as payer (AOR 1.66, 95% CI 1.01-2.75), comorbid mental disorders (e.g., psychoses AOR 3.34, 95% CI 1.35-8.26), and multiple prescriptions (4 or more prescriptions AOR 4.48, 95% CI 2.08-9.64) were more likely to have an AAP prescription. The off-label use of AAPs in children and adolescents is prevalent in the United States. Our study raises questions about the potential misuse of AAPs in the population. PMID- 27281083 TI - Treatment of necrotizing acute pancreatitis with peritoneal lavage and dialysis by a new simplified technique insert catheters: One retrospective study. AB - Peritoneal lavage and dialysis is an approach to treat necrotizing acute pancreatitis as it removes dialyzable toxins and reduces severe metabolic disturbances. Successful catheter implantation is important for delivering adequate peritoneal lavage and dialysis. The aim of the present study was to describe a new modified percutaneous technique for the placement of peritoneal dialysis catheters and assess the effectiveness and safety of peritoneal lavage and dialysis used for treatment of necrotizing acute pancreatitis. We conducted a retrospective data review of 35 patients of necrotizing acute pancreatitis from January 2010 to December 2014 in Jilin City Central Hospital and The First Affiliated Hospital of ZheJiang University. In total, 18 patients underwent peritoneal lavage and dialysis after inserting catheters by our new technique (group A), whereas 17 patients underwent ultrasound-guided percutaneous catheter drainage (group B). By analyzing the patients' data, the drainage days and mean number of hours between the debut of the symptoms and the hospital admission were lower in group A (P < 0.05, P < 0.05, respectively). The complication rate of 5.6 and 17.6%, respectively (P = 0.261), and a mortality rate of 16.7 and 5.9% for each group, respectively (P = 0.316). Likewise, hospitalization time was similar for the group A: 31 +/- 25.3 days compared with 42.8 +/- 29.4 days in the group B (P = 0.211). Peritoneal lavage and dialysis can be used in necrotizing acute pancreatitis, and our new modified percutaneous technique offers the same complication and mortality rate as ultrasound-guided drainage but with a shorter drainage days. PMID- 27281082 TI - Antibiotic prescribing of village doctors for children under 15 years with upper respiratory tract infections in rural China: A qualitative study. AB - The aim of this study was to explore the knowledge, attitudes, and practices of village doctors regarding the prescribing of antibiotics for children under 15 years with upper respiratory tract infections (URTIs) in rural China. Twelve focus group discussions (FGDs) were conducted in Xianning, a prefecture-level city in rural China, during December 2014. We conducted 6 FGDs with 35 village doctors, 3 with 13 primary caregivers (11 parents), and 3 with 17 directors of township hospitals, county-level health bureaus, county-level Centers for Disease Control and Prevention, or county-level Chinese Food and Drug Administration offices. Audio records of the interviews were transcribed verbatim and analyzed using the thematic analysis approach. Participants believed that unnecessary antibiotic prescribing for children under 15 years with The occurrence of URTIs was a problem in village clinics in rural China. The discussions revealed that most of the village doctors had inadequate knowledge and misconceptions about antibiotic use, which was an important factor in the unnecessary prescribing. Village doctors and directors reported that the doctors' fear of complications, the primary caregivers' pressure for antibiotic treatment, and the financial considerations of patient retention were the main factors influencing the decision to prescribe antibiotics. Most of the primary caregivers insisted on antibiotics, even when the village doctors were reluctant to prescribe them, and they preferred to go to see those village doctors who prescribed antibiotics. The interviewees also gave their opinions on what would be the most effective measures for optimizing antibiotic prescriptions; these included educational/training campaigns, strict regulations on antibiotic prescription, and improved supervision. Findings emphasized the need to improve the dissemination of information and training/education, and implement legislation on the rational use of antibiotics. And it also provided helpful information to guide the design of more effective interventions to promote prudent antibiotic use and good antimicrobial stewardship. PMID- 27281084 TI - Which is your choice for prolonging the analgesic duration of single-shot interscalene brachial blocks for arthroscopic shoulder surgery? intravenous dexamethasone 5 mg vs. perineural dexamethasone 5 mg randomized, controlled, clinical trial. AB - The aim of this study was to compare the effect of intravenous (I.V.) dexamethasone with that of perineural dexamethasone on the prolongation of analgesic duration of single-shot interscalene brachial plexus blocks (SISB) in patients undergoing arthroscopic shoulder surgery. We performed a prospective, randomized, double-blind, placebo-controlled study. Patients undergoing elective arthroscopic shoulder surgery with ultrasound-guided SISB were enrolled and randomized into 2 groups. A total volume of 12 mL of the study drug was prepared with a final concentration of 0.5% ropivacaine. In the I.V. group, patients received SISB using ropivacaine 5 mg mL with normal saline (control) with dexamethasone 5 mg I.V. injection. In the perineural group, patients received SISB using ropivacaine 5 mg mL with dexamethasone 5 mg, with normal saline 1 mL I.V. injection. The primary outcome was the time to the first analgesic request, defined as the time between the end of the operation and the first request of analgesics by the patient. The secondary outcomes included patient satisfaction scores, side effects, and neurological symptoms. Patients were randomly assigned to 1 of the 2 groups using a computer-generated randomization table. An anesthesiologist blinded to the group assignments prepared the solutions for injection. The patients and the investigator participating in the study were also blinded to the group assignments. One hundred patients were randomized. Data were analyzed for 99 patients. One case in the I.V. group was converted to open surgery and was therefore not included in the study. Perineural dexamethasone significantly prolonged analgesic duration (median, standard error: 1080 minutes, 117.5 minutes) compared with I.V. dexamethasone (810 minutes, 48.1 minutes) (P = 0.02). There were no significant differences in side effects, neurological symptoms, or changes in blood glucose values between the 2 groups. Our results show that perineural dexamethasone 5 mg is more effective than I.V. dexamethasone 5 mg with regard to analgesic duration of SISB for arthroscopic shoulder surgery. PMID- 27281085 TI - Elevated neutrophil to lymphocyte ratio predicts mortality in medical inpatients with multiple chronic conditions. AB - Neutrophil to lymphocyte ratio (NLR) is an easy measurable laboratory marker used to evaluate systemic inflammation. Elevated NLR is associated with poor survival and increased morbidity in cancer and cardiovascular disease. However, the usefulness of NLR to predict morbidity and mortality in a hospital setting for patients with multiple chronic conditions has not been previously examined. In this study, we investigate the association between NLR and mortality in multimorbid medical inpatients. Two hundred thirty medical in-patients with chronic conditions were selected from a single academic medical center in Taiwan. Retrospective NLRs were calculated from routine full blood counts previously obtained during the initial hospital admission and at the time of discharge. Self rated health (using a single-item question), medical disorders, depressive symptoms, and medical service utilization over a 1-year period were included in the analyses. Mortality outcomes were ascertained by reviewing electronic medical records and follow-up. The mortality rate at 2-year follow-up was 23%. Depression (odds ratio [OR] 1.9 [95% CI 1.0-3.7]), poor self-rated health (OR 2.1 [95% CI 1.1-3.9]), being hospitalized 2 or more times in the previous year (OR 2.3 [95% CI 1.2-4.6]), metastatic cancer (OR 4.7 [95% CI 2.3-9.7]), and chronic liver disease (OR 4.3 [95% CI 1.5-12.1]) were associated with 2-year mortality. The median (interquartile range) NLR at admission and discharge were 4.47 (2.4-8.7) and 3.65 (2.1-6.5), respectively. Two-year mortality rates were higher in patients with an elevated NLR at admission (NLR <3 = 15.5%, NLR >3 = 27.6%) and discharge (NLR < 3 = 14.7%, NLR >3 = 29.1%). Multivariate logistic regression demonstrated that an elevated NLR >3.0 at admission (OR 2.3 [95% CI 1.0-5.2]) and discharge (OR 2.3 [95% CI 1.1-5.0]) were associated with mortality independent of baseline age, sex, education, metastatic cancer, liver disease, depression, and previous hospitalization. Increased NLR is associated with mortality among medical inpatients with multiple chronic conditions. NLR may provide added value to predict both risk of mortality for the inpatients with chronic conditions, in addition to allowing predictions of likely hospital service needs such as re admissions that are associated with long-term mortality. PMID- 27281086 TI - In vivo confocal microscopy of meibomian glands in primary blepharospasm: A prospective case-control study in a Chinese population. AB - The aim of the study was to evaluate the morphological changes of meibomian glands (MGs) in primary blepharospasm (PBS) by in vivo laser scanning confocal microscopy (LSCM) and to investigate the correlations between clinical data of PBS and LSCM parameters of MGs. This prospective and case-control study recruited 30 consecutive PBS patients and 30 age- and gender-matched healthy controls. After questionnaire assessments of ocular surface disease index (OSDI), Jankovic rating scale, and blepharospasm disability index, all subjects underwent blink rate evaluation, tear film break-up time (TBUT), corneal fluorescein staining (CFS), Schirmer test, MG expressibility, meibum quality, MG dropout, and LSCM examination of the MGs. The main LSCM outcomes included the mean MG acinar area and density, orifice diameter, meibum secretion reflectivity, acinar irregularity, and inhomogeneity of interstice and acinar wall. The PBS patients had significantly higher blink rate, higher OSDI and CFS scores, lower TBUT and Schirmer test value, and worse MG expressibility than the controls (All P < 0.05), whereas meibum quality showed no difference (P > 0.05). The PBS patients showed lower values of MG acinar area, orifice diameter and meibum secretion reflectivity, and higher scores of acinar irregularity and inhomogeneity of interstices than the controls (All P < 0.05). For the PBS patients, the severity of blepharospasm evaluated by JCR scale was strong correlated with MG acinar area (P < 0.001), orifice diameter (P = 0.002), meibum secretion reflectivity (P = 0.002), and MG acinar irregularity (P = 0.013). The MG expressibility was significantly correlated to MG acinar area (P = 0.039), orifice diameter (P < 0.001), and MG acinar irregularity (P = 0.014). The OSDI score was moderate correlated with MG acinar irregularity (P = 0.016), whereas the TBUT value was positively correlated with MG acinar area (P = 0.045) and negatively correlated to MG acinar irregularity (P = 0.016). The CFS score was negatively correlated to MG orifice diameter (P = 0.008). The LSCM provided a noninvasive tool for in vivo histopathologic studies of MGs in PBS patients. The excessive constriction of lid muscles closely related to MG morphological alterations of PBS, which offered a new research approach to interpret the interactional mechanism between dry eye and PBS. PMID- 27281087 TI - The clinical outcomes and predictive factors for in-hospital mortality in non neutropenic patients with candidemia. AB - Recent epidemiologic studies have showed that candidemia is an important nosocomial infection in hospitalized patients. The majority of candidemia patients were non-neutropenic rather than neutropenic status. The aim of this study was to determine the clinical outcome of non-neutropenic patients with candidemia and to measure the contributing factors for mortality. A total of 163 non-neutropenic patients with candidemia during January 2010 to December 2013 were retrospectively enrolled. The patients' risk factors for mortality, clinical outcomes, treatment regimens, and Candida species were analyzed. The overall mortality was 54.6%. Candida albicans was the most frequent Candida species (n = 83; 50.9% of patients). Under multivariate analyses, hemodialysis (OR, 4.554; 95% CI, 1.464-14.164) and the use of amphotericin B deoxycholate (OR, 8.709; 95% CI, 1.587-47.805) were independent factors associated with mortality. In contrast, abdominal surgery (OR, 0.360; 95% CI, 0.158-0.816) was associated with a better outcome. The overall mortality is still high in non-neutropenic patients with candidemia. Hemodialysis and use of amphotericin B deoxycholate were independent factors associated with mortality, whereas prior abdominal surgery was associated with a better outcome. PMID- 27281088 TI - Laparoscopic cholecystectomy for acute cholecystitis: early or delayed?: Evidence from a systematic review of discordant meta-analyses. AB - The laparoscopic cholecystectomy (LC) is an important approach of treating acute cholecystitis and the timing of performing this given treatment is associated with clinical outcomes. Although several meta-analyses have been done to investigate the optimal timing of implementing this treatment, the conflicting findings from these meta-analyses still confuse decision-making. And thus, we performed this systematic review to assess discordant meta-analyses and generate conclusive findings to facilitate informed decision-making in clinical context eventually. We electronically searched the PubMed, Cochrane Library, and EMBASE to include meta-analysis comparing early (within 7 days of the onset of symptoms) with delayed LC (at least 1 week after initial conservative treatment) for acute cholecystitis through August 2015. Two independent investigators completed all tasks including scanning and appraising eligibility, abstracting essential information using prespecified extraction form, assessing methodological quality using Oxford Levels of Evidence and Assessment of Multiple Systematic Reviews (AMSTAR) tool, and assessing the reporting quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), as well as implementing Jadad algorithm in each step for the whole process. A heterogeneity degree of <=50% is accepted. Seven eligible meta-analyses were included eventually. Only one was Level I of evidence and remaining studies were Level II of evidence. The AMSTAR scores varied from 8 to 11 with a median of 9. The PRISMA scores varied from 19 to 26. The most heterogeneity level fell into the desired criteria. After implementing Jadad algorithm, 2 meta-analyses with more eligible RCTs were selected based on search strategies and implication of selection. The best available evidence indicated a nonsignificant difference in mortality, bile duct injury, bile leakage, overall complications, and conversion to open surgery, but a significant reduction in wound infection, hospitalization, and operation duration and improvement of the quality of life when compared early LC with delayed LC. However, number of work days lost, hospital costs, and patient satisfaction are warranted to be assessed further. With the best available evidence, we recommend early LC to be as the standard treatment option in treating acute cholecystitis. PMID- 27281089 TI - The biophysical characterization of the first SCN5A mutation R1512W identified in Chinese sudden unexplained nocturnal death syndrome. AB - Increasing evidence observed in clinical phenotypes show that abrupt breathing disorders during sleep may play an important role in the pathogenesis of sudden unexplained nocturnal death syndrome (SUNDS). The reported Brugada syndrome causing mutation R1512W in cardiac sodium channel alpha subunit encoded gene SCN5A, without obvious loss of function of cardiac sodium channel in previous in vitro study, was identified as the first genetic cause of Chinese SUNDS by us. The R1512W carrier was a 38-year-old male SUNDS victim who died suddenly after tachypnea in nocturnal sleep without any structural heart disease. To test our hypothesis that slight acidosis conditions may contribute to the significant loss of function of mutant cardiac sodium channels underlying SUNDS, the biophysical characterization of SCN5A mutation R1512W was performed under both extracellular and intracellular slight acidosis at pH 7.0. The cDNA of R1512W was created using site-directed mutagenesis methods in the pcDNA3 plasmid vector. The wild type (WT) or mutant cardiac sodium channel R1512W was transiently transfected into HEK293 cells. Macroscopic voltage-gated sodium current (INa) was measured 24 hours after transfection with the whole-cell patch clamp method at room temperature in the HEK293 cells. Under the baseline conditions at pH 7.4, R1512W (-175 +/- 15 pA/pF) showed about 30% of reduction in peak INa compared to WT ( 254 +/- 23 pA/pF, P < 0.05). Under the acidosis condition at pH 7.0, R1512W (-130 +/- 17 pA/pF) significantly decreased the peak INa by nearly 50% compared to WT ( 243 +/- 23 pA/pF, P < 0.005). Compared to baseline condition at pH 7.4, the acidosis at pH 7.0 did not affect the peak INa in WT (P > 0.05) but decreased peak INa in R1512W (P < 0.05). This initial functional study for SCN5A mutation in the Chinese SUNDS victim revealed that the acidosis aggravated the loss of function of mutant channel R1512W and suggested that nocturnal sleep disorders associated slight acidosis may trigger the lethal arrhythmia underlying the sudden death of SUNDS cases in the setting of genetic defect. PMID- 27281090 TI - Usefulness of voxel-based lesion mapping for predicting motor recovery in subjects with basal ganglia hemorrhage: A preliminary study with 2 case reports. AB - It is important to estimate motor recovery in the early phase after stroke. Many studies have demonstrated that both diffusion tensor tractography (DTT) and motor evoked potentials (MEP) are valuable predictors of motor recovery, but these modalities do not directly reflect the status of the injured gray matter. We report on 2 subjects with basal ganglia hemorrhage who showed similar DTT and MEP findings, but had markedly different clinical outcomes. Specifically, Subject 1 showed no improvement in motor function, whereas Subject 2 exhibited substantial improvement 7 weeks after onset. To determine if differences in gray matter might lend insight into these different outcomes, we analyzed gray matter lesions of the 2 subjects using a novel voxel-based lesion mapping method. The lesion of Subject 1 mainly included the putamen, thalamus, and Heschl's gyri, indicating extension of the hemorrhage in the posterior direction. In contrast, the lesion of Subject 2 mainly included the putamen, insula, and pallidum, indicating that the hemorrhage extended anterior laterally. These differential findings suggest that voxel-based gray matter lesion mapping may help to predict differential motor recovery in subjects with basal ganglia hemorrhage with similar DTT and MEP findings. PMID- 27281091 TI - Genetic variants associated with lean and obese type 2 diabetes in a Han Chinese population: A case-control study. AB - Type 2 diabetes (T2D) is highly phenotypically heterogeneous. Genetics of the heterogeneity of lean and obese T2D is not clear. The aim of the present study was to identify the associations of T2D-related genetic variants with the risks for lean and obese T2D among the Chinese Han population. A case-control study consisting of 5338 T2D patients and 4663 normal glycemic controls of Chinese Han recruited in the Chinese National Diabetes and Metabolic Disorders Study was conducted. T2D cases were identified according to the 1999 World Health Organization criteria. Lean T2D was defined as T2D patient with a body mass index (BMI) <23 kg/m, whereas obese T2D was defined as T2D patient with a BMI >=28 kg/m. Twenty-five genome-wide association studies previously validated T2D related single-nucleotide polymorphisms (SNPs) were genotyped. A genotype risk score (GRS) based on the 25 SNPs was created. After adjusting for multiple covariates, SNPs in or near CDKAL1, CDKN2BAS, KCNQ1, TCF7L2, CDC123/CAMK1D, HHEX, and TCF2 were associated with the risk for lean T2D, and SNPs in or near KCNQ1 and FTO were associated with the risk for obese T2D. The results showed that the GRS for 25 T2D-related SNPs was more strongly associated with the risk for lean T2D (Ptrend = 2.66 * 10) than for obese T2D (Ptrend = 2.91 * 10) in our study population. Notably, the T2D GRS contributed to lower obesity-related measurements and greater beta-cell dysfunction, including lower insulin levels in oral glucose tolerance test, decreased insulinogenic index, and Homeostasis Model Assessment for beta-cell Function. In conclusion, our findings identified T2D related genetic loci that contribute to the risk of lean and obese T2D individually and additively in a Chinese Han population. Moreover, the study highlights the contribution of known T2D genomic loci to the heterogeneity of lean and obese T2D in Chinese Hans. PMID- 27281092 TI - World Health Organization (WHO) surgical safety checklist implementation and its impact on perioperative morbidity and mortality in an academic medical center in Chile. AB - Health care organizations are unsafe. Numerous centers have incorporated the WHO Surgical Safety Checklist in their processes with good results; however, only limited information is available about its effectiveness in Latin America. We aimed to evaluate the impact of the checklist implementation on the in-hospital morbidity and mortality rate in a tertiary health care center. After Institutional review board approval, and using data from our hospital administrative records, we conducted a retrospective analysis of all surgical encounters (n = 70,639) over the period from January 2005 to December 2012. Propensity scoring (PS) methods (matching and inverse weighting) were used to compare the pre and postintervention period, after controlling for selection bias. After PS matching (n = 29,250 matched pairs), the in-hospital mortality rate was 0.82% [95% confidence interval (CI), 0.73-0.92] before and 0.65% (95% CI, 0.57-0.74) after checklist implementation [odds ratio (OR) 0.73; 95% CI, 0.61 0.89]. The median length of stay was 3 days [interquartile range (IQR), 1-5] and 2 days (IQR, 1-4) for the pre and postchecklist period, respectively (P < 0.01).This is the first Latin American study reporting a decrease in mortality after the implementation of the WHO Surgical Checklist in adult surgical patients. This is a strong and simple tool to make health care safer, especially in developing countries. PMID- 27281093 TI - SafAIRway: an airway training for pulmonologists performing a flexible bronchoscopy with nonanesthesiologist administered propofol sedation: A prospective evaluation. AB - Nonanesthesiologist administered propofol (NAAP) sedation for flexible bronchoscopy is controversial, because there is no established airway management (AM) training for pulmonologists. The aim was to investigate the performance and acceptance of a proposed AM algorithm and training for pulmonologists performing NAAP sedation. The algorithm includes using 3 maneuvers including bag mask ventilation (BMV), laryngeal tube (LT), and needle cricothyrotomy (NCT). During training (consisting of 2 sessions with a break of 9 weeks in between), these maneuvers were demonstrated and exercised, followed by 4 consecutive attempts to succeed with each of these devices. The primary outcome was the improvement of completion time needed for a competent airway. Secondary outcomes were the trainees' overall reactions to the training and algorithm, and the perceptions of psychological safety (PS). The 23 staff members of the Department of Pulmonology performed a total of 552 attempts at AM procedures (4 attempts at each of the 3 maneuvers in 2 sessions), and returned a total of 42 questionnaires (4 questionnaires were not returned). Median completion times of LT and NCT improved significantly between Sessions 1 and 2 (P = 0.005 and P = 0.04, respectively), whereas BMV was only marginally improved (P = 0.05). Trainees perceived training to be useful and expressed satisfaction with this training and the algorithm. The perception of PS increased after training. An AM algorithm and training for pulmonologists leads to improved technical AM skills, and is considered useful by trainees and raised their perception of PS during training. It thus represents a promising program. PMID- 27281094 TI - Correlation of platelets count with endoscopic findings in a cohort of Egyptian patients with liver cirrhosis. AB - Screening endoscopy is recommended for early detection of esophageal varices (EVs) in cirrhotic patients with portal hypertension. However, this approach is limited by its invasiveness and cost. The aim of the study was to determine if platelet count can predict the presence of EVs, especially large (grade III, IV) EVs in need of prophylactic therapy, in a cohort of Egyptian patients with liver cirrhosis. In all, 110 patients with cirrhosis were prospectively analyzed. The presence of medium or large EVs was correlated with patients' platelet count and FIB-4. Esophageal varices were present in 87 (79.09%) patients. Among those with thrombocytopenia (platelet level below 150,000), 25.97% (20 patients) and 27.27% (21 patients) had EV grade II and EV grade III or IV, respectively. Whereas in patients in whom the platelet count was above 150,000, only 21.21% (7 patients) and 9.09% (3 patients) of patients had grade II EV and EV grade III or IV, respectively. A platelet count cut-off value of 149,000 was found to have specificity of 82% and sensitivity 39% for detection of presence of varices. A FIB-4 cut-off value of 3.175 was found to have an 83.3% sensitivity and 39.5% specificity in detecting large (grade III, IV) EVs. Platelet count is a noninvasive parameter with high accuracy for prediction of EVs. Cirrhotic patients with normal platelet counts (above 150,000), especially in financially deprived developing countries, can avoid screening endoscopy as they are at a low risk for variceal bleeding, and presence of large EVs in these patients is much less common than in those with thrombocytopenia. A 3.175 cut-off value of FIB-4 could be useful as a noninvasive predictor of large varices requiring prophylactic banding in cirrhotic patients. PMID- 27281095 TI - Circulating interleukin-6 and rheumatoid arthritis: A Mendelian randomization meta-analysis. AB - Interleukin-6 (IL-6), as a pleiotropic cytokine, has been demonstrated to be closely associated with the pathogenisis of rheumatoid arthritis (RA). However, whether this association is causal or not remains unclear, because of the multifactorial role of IL-6 and related confounding factors. We aimed to evaluate the causal relevance between circulating IL-6 levels and the risk of RA through meta-analytical Mendelian randomization approach. IL-6 gene -174G/C variant was selected as an instrument in this Mendelian randomization meta-analysis. Article identification and data collection were conducted in duplicate and independently by 2 authors. The STATA software was used for data analysis. In total, 15 and 5 articles on the association of the -174G/C variant with RA risk and circulating IL-6 level, respectively, were included. The overall analysis showed that C allelic and GC+CC genotype were significantly with 1.59-fold (95% CI: 1.19-2.14) and 1.63-fold (95% CI: 1.17-2.26) increased risk of developing RA, respectively. Asian populations showed stronger association with 4.55-fold (95% CI: 1.62 12.75), 1.84-fold (95% CI: 1.13-2.99), and 4.69-fold (95% CI: 1.68-13.14) increased RA risk in carriers of -174C allelic, CC, and GC+CC genotype, respectively. Carriers of GC+CC genotype showed significant reduction in the circulating IL-6 level compared with GG carriers (WMD = -0.77; 95% CI: -1.16 to 0.38; P = 0.000) in overall populations. Mendelian randomization presented 6% and 22% increased risk of RA with 0.1 pg/mL reduction of circulating IL-6 level in overall and Asian populations, respectively. This Mendelian randomization meta analysis demonstrated that the long-term genetically reduced circulating IL-6 level might be causally related to a higher risk of RA, especially in Asian populations. PMID- 27281096 TI - The association between human papillomavirus infection and female lung cancer: A population-based cohort study. AB - Lung cancer is the leading cause of cancer deaths among Taiwanese women. Human papillomavirus (HPV) has been detected in lung cancer tissues. The aim of this study was to investigate the association between HPV infection and lung cancer among the Taiwanese women. The analytical data were collected from the longitudinal health insurance databases (LHID 2005 and 2010) of the National Health Insurance Research Database (NHIRD). The study participants were 30 years and older and included 24,162 individuals who were identified with HPV infection from 2001 to 2004 and 1,026,986 uninfected individuals. Lung cancer incidence among infected and uninfected individuals was compared using the univariate and multivariate regression models. Among the total participants, 24,162 individuals were diagnosed with HPV. After adjusting for age, gender, low income, residential area, and comorbidity, the risk of lung cancer was higher in women (hazard ratio [HR] 1.263, 95% CI 1.015-1.571), while all cancer risks were high in both men and women with corresponding hazard ratios (HR) of 1.161 (95% CI 1.083-1.245) and HR 1.240 (95% CI 1.154-1.331), respectively. This study showed a significant increase in lung cancer risk among Taiwanese women who were exposed to HPV infection. PMID- 27281097 TI - Noninvasive fat quantification of the liver and pancreas may provide potential biomarkers of impaired glucose tolerance and type 2 diabetes. AB - The aim of the study is to investigate if the fat content of the liver and pancreas may indicate impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM). A total of 83 subjects (34 men; aged 46.5 +/- 13.5 years) were characterized as T2DM, IGT, or normal glucose tolerant (NGT). NGT individuals were stratified as <40 or >=40 years. Standard laboratory tests were conducted for insulin resistance and beta-cell dysfunction. The magnetic resonance imaging Dixon technique was used to determine fat distribution in the liver and pancreas. Correlations among liver and pancreatic fat volume fractions (LFVFs and PFVFs, respectively) and laboratory parameters were analyzed. Among the groups, fat distribution was consistent throughout sections of the liver and pancreas, and LFVFs closely correlated with PFVFs. LFVFs correlated more closely than PFVFs with insulin resistance and beta-cell function. Both the LFVFs and PFVFs were the highest in the T2DM patients, less in the IGT, and least in the NGT; all differences were significant. The PFVFs of the NGT subjects >=40 years were significantly higher than that of those <40 years. The fat content of the liver and pancreas, particularly the liver, may be a biomarker for IGT and T2DM. PMID- 27281098 TI - The relationships of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease. AB - Hypertension, blood pressure variation, and resistant hypertension have close relations to sleep apnea, which lead to target organ damage, including the kidney. The complex relationships between sleep apnea and blood pressure cause their interactions with chronic kidney disease ambiguous. The aim of the study was to elucidate the separate and joint effects of sleep apnea, hypertension, and resistant hypertension on chronic kidney disease. A cross-sectional study was done to see the associations of sleep apnea, hypertension, and resistant hypertension with chronic kidney disease in 998 subjects underwent overnight polysomnography without device-therapy or surgery for their sleep-disordered breathing. Multivariate logistic regression was used to analyze the severity of SA, hypertension stage, resistant hypertension, and their joint effects on CKD. The multivariable relative odds (95% CI) of chronic kidney disease for the aged (age >=65 years), severe sleep apnea, stage III hypertension, and resistant hypertension were 3.96 (2.57-6.09) (P < 0.001), 2.28 (1.13-4.58) (P < 0.05), 3.55 (1.70-7.42) (P < 0.001), and 9.42 (4.22-21.02) (P < 0.001), respectively. In subgroups analysis, the multivariable relative odds ratio of chronic kidney disease was highest in patients with both resistant hypertension and severe sleep apnea [13.42 (4.74-38.03)] (P < 0.001). Severe sleep apnea, stage III hypertension, and resistant hypertension are independent risk factors for chronic kidney disease. Patients with both severe sleep apnea and resistant hypertension have the highest risks. PMID- 27281099 TI - Benign incidental findings of osteopoikilosis on Tc-99m MDP bone SPECT/CT: A case report and literature review. AB - Osteopoikilosis is a benign but rare condition characterized by bone islands throughout the osseous tissue, which could be easily confused with bone metastasis. We present a case of a 37-year-old man presented to orthopedic outpatient clinic with right hip pain for 2 weeks. There were multiple, small punctate lesions scattered throughout the skeleton on radiograph. Subsequent Tc 99m methylene diphosphonate (MDP) bone scan with pelvic single-photon emission computed tomography (SPECT)/computed tomography (CT) showed multiple enostoses without abnormal focal MDP uptake. Therefore, clinical diagnosis was compatible with osteopoikilosis while bone metastasis was unlikely. The symptoms then improved by conservative treatments. Osteopoikilosis is usually an incidental finding on radiograph or CT, and a normal MDP confirmed the diagnosis by excluding bone metastasis. It is important for clinicians to recognize the specific image features to prevent further unnecessary interventions. In addition, bone SPECT/CT could also make the diagnosis in one step. PMID- 27281100 TI - Gallbladder bleeding-related severe gastrointestinal bleeding and shock in a case with end-stage renal disease: A case report. AB - Gallbladder (GB) bleeding is very rare and it is caused by cystic artery aneurysm and rupture, or GB wall rupture. For GB rupture, the typical findings are positive Murphy's sign and jaundice. GB bleeding mostly presented as hemobilia. This is the first case presented with severe GI bleeding because of GB rupture related GB bleeding. After comparing computed tomography, one gallstone spillage was noticed. In addition to gallstones, uremic coagulopathy also worsens the bleeding condition. This is also the first case that patients with GB spillage related rupture and bleeding were successfully treated by nonsurgical management. Clinicians should bear in mind the rare causes of GI bleeding. Embolization of the bleeding artery should be attempted as soon as possible. PMID- 27281101 TI - Clostridium difficile infection in a French university hospital: Eight years of prospective surveillance study. AB - The epidemiology of Clostridium difficile infection (CDI) has changed with an increase in incidence and severity. Prospective surveillance was therefore implemented in a French university hospital to monitor the characteristics of patients at risk and to recognize local trends. Between 2007 and 2014, all hospitalized patients (>=18 years) with CDI were included. During the survey, the mean incidence rate of CDI was 2.9 per 10,000 hospital-days. In all, 590 patients were included. Most of the episodes were healthcare-associated (76.1%). The remaining cases were community-acquired (18.1%) and unknown (5.9%). The comparison with healthcare-associated cases showed that the community-acquired group had a lower rate of antimicrobial exposure (P < 0.001), proton pump inhibitor (P < 0.001), and immunosuppressive drugs (P = 0.02). Over the study period, death occurred in 61 patients (10.3%), with 18 (29.5%) being related to CDI according to the physician in charge of the patient. Active surveillance of CDI is required to obtain an accurate picture of the real dimensions of CDI. PMID- 27281102 TI - Bleeding events associated with fibrinolytic therapy and primary percutaneous coronary intervention in patients with STEMI: A systematic review and meta analysis of randomized controlled trials. AB - From the year 1986 onwards, several studies have been published focusing on the comparison between fibrinolysis and primary percutaneous coronary intervention (PPCI) in patients with ST segment elevated myocardial infarction (STEMI). However, because antiplatelet and anticoagulating medications are used in approximation, before and during these procedures, bleeding events have been reported to be associated with both reperfusion therapies. This study aimed to compare the bleeding events associated with fibrinolytic therapy and primary angioplasty in patients with STEMI. Randomized controlled trials (RCTs) comparing fibrinolysis and primary angioplasty in patients with STEMI were searched from Medline, PubMed, EMBASE, and the Cochrane databases. Bleeding complications following 30 days from hospitalization were considered as the primary clinical endpoints in this study. Secondary endpoints included all-cause mortality, re infarction, stroke, and shock. Antiplatelet and anticoagulating drugs used during these 2 different procedures were compared. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and the pooled analyses were performed with RevMan 5.3 software. Twelve studies involving 10 RCTs consisting of a total number of 5561 patients (2784 patients from the fibrinolysis group and 2777 patients from the PPCI group) were included in this meta-analysis. Our results showed no significant difference in the overall bleeding complications during a 30-day period between these 2 reperfusion therapies with OR 1.02; 95% CI 0.89 to 1.17, P = 0.78. Nonintracranial bleeding was also not statistically significant with OR 0.85; 95% CI 0.70 to 1.04, P = 0.12. However, fibrinolytic therapy was associated with a significantly higher rate of intracranial bleeding with OR 0.17; 95% CI 0.06 to 0.50, P = 0.001 than PPCI. In addition, death, re infarction, and stroke significantly favored primary angioplasty. According to the results of this study, even if the rate of nonintracranial bleeding was not statistically significant between these 2 reperfusion therapies, fibrinolytic therapy was associated with a significantly higher rate of intracranial bleeding than PPCI. In addition, PPCI was associated with a significantly lower rate of death, reinfarction, and stroke. Therefore, PPCI should be recommended in patients with STEMI, especially in PCI-capable hospitals. PMID- 27281103 TI - The use of gabapentin in the management of postoperative pain after total knee arthroplasty: A PRISMA-compliant meta-analysis of randomized controlled trials. AB - Pain management after total knee arthroplasty (TKA) varies and has been widely studied in recent years. Some randomized controlled studies have carried out to evaluate the effects of gabapentin on pain relief after TKA. However, no solid result was made about it. The purpose of this Meta-Analysis of Randomized Controlled Trials (RCTs) was to estimate the overall effect of pain control of gabapentin versus placebo after a TKA. An electronic-based search using the following databases: PubMed, EMBASE, Ovid MEDLINE, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trial from 1966 to June 2015. RCTs involving gabapentin and placebo for total knee arthroplasty were included. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Six trials with 859 participants met the inclusion criteria. The primary endpoint was cumulative narcotic consumption and the visual analog scale scores at 12 hours, 24 hours, and 48 hours, postoperatively. The knee flexion degree and treatment side effects were also compiled to evaluate the safety of gabapentin. After testing for the heterogeneity and publication bias among studies, data were aggregated for random effects modeling when necessary. There was a significant decrease in morphine consumption at 12 hours (MD = -4.69, 95% CI: -7.18 to -2.21, P = 0.0002), 24 hours (MD = -5.30, 95% CI: -9.94 to -0.66, P = 0.03), and 48 hours (MD = -17.80, 95% CI: -31.95 to -3.64, P = 0.01), respectively. Compared with the control group, the rate of pruritus was less in the gabapentin group (RR 0.20, 95% CI 0.10 to 0.38, P = 0.00). In summary, the administration of gabapentin was effective in decreasing postoperative narcotic consumption and the incidence of pruritus. There was a high risk of selection bias and a higher heterogeneity of knee flexion range in this analysis. More high-quality large randomized controlled trials with long follow-up period are necessary for proper comparisons of the efficacy and safety of gabapentin with placebo.Systematic review registration number: No. PMID- 27281104 TI - Therapeutic bronchoscopic interventions for malignant airway obstruction: A retrospective study from experience on 547 patients. AB - There is no definitive consensus about the factors affecting the choice of interventional bronchoscopy in the management of malignant airway obstruction. The present study defines the choice of the interventional bronchoscopic modality and analyzes the factors influencing survival in patients with malignant central airway obstruction. Totally, over 7 years, 802 interventional rigid bronchoscopic procedures were applied in 547 patients having malignant airway obstruction. There was a significant association between the type of stent and the site of the lesion in the present study. Patients with tracheal involvement and/or involvement of the main bronchi had the worst prognosis. The sites of the lesion and endobronchial treatment modality were independent predictors of survival in the present study. The selection of different types of airway stents can be considered on the base of site of the lesion. Survival can be estimated based on the site of the lesion and endobronchial brochoscopic modality used. PMID- 27281105 TI - Nonalcoholic fatty liver disease is associated with excessive calorie intake rather than a distinctive dietary pattern. AB - We aimed to assess the dietary patterns associated with nonalcoholic fatty liver disease (NAFLD) and the efficacy of dietary interventions in a real-life setting at a tertiary medical center in Northern Germany.Clinical and laboratory data as well as data obtained by a semiquantitative food frequency questionnaire of 55 consecutive patients diagnosed with NAFLD were compared to an age and gender matched cohort of 88 healthy individuals by univariate analysis. The efficacy of the dietary intervention was assessed in a subgroup of 24 NAFLD patients 6 months after receiving dietary advice. Macronutritional components of the diet were normalized for absolute daily energy intake.NAFLD patients consumed more calories per day as compared with healthy controls (P <0.001). The absolute amounts of most nutritional components ingested by NAFLD patients were higher than those of the controls. However, there were no significant differences with regards to the relative consumption of carbohydrates (P = 0.359), fat (P = 0.416), and fructose (P = 0.353) per 1000 kcal energy intake. NAFLD patients displayed a higher intake of glucose/1000 kcal (P = 0.041) and protein/1000 kcal (P = 0.009) but a lower intake of fibers/1000 kcal (P < 0.001) and mineral nutrients/1000 kcal (P = 0.001) than healthy controls. In the longitudinal analysis patients significantly reduced their caloric intake and their ALT levels improved 6 months after the dietary counselling (P < 0.001).Our data from a German real-life cohort demonstrate that dietary patterns of patients with NAFLD display great variability and little disease specificity, while the most distinctive feature compared with healthy controls was higher energy intake in NAFLD patients. PMID- 27281106 TI - A network signal amplification strategy of ultrasensitive photoelectrochemical immunosensing carcinoembryonic antigen based on CdSe/melamine network as label. AB - Taking advantage of CdSe/melamine network as label and Au-TiO2 as substrate, this work developed a novel kind of signal amplification strategy for fabricating photoelectrochemical (PEC) immunoassay. The melamine, a star-shaped triamino molecule, was firstly used for readily capturing CdSe QDs and forming a CdSe/melamine network, which was formed through strong interactions between the carboxyl groups of TGA-stabilized CdSe QDs and the three amino groups of each melamine molecule. In this strategy, the primary antibody (Ab1) was immobilized onto Au-TiO2 substrate, which made the photoelectric conversion efficiency increase significantly. After the formed Ab2-CdSe/melamine network labels were captured onto the electrode surface via the specific antibody-antigen interaction, the photoelectric activity could be further enhanced via the interaction between the Au-TiO2 substrate and CdSe/melamine network. Due to this amplification of PEC signals and the special structure of the label, the fabricated PEC immunosensor was applied for sensitive and specific detection of cancer biomarker carcinoembryonic antigen (CEA), and displayed a wide linear range (0.005-1000ngmL(-1)) and low detection limit (5pgmL(-1)). In addition, the immunosensor was performed with good stability and reproducibility, and the results to analyze human serum samples were satisfactory. PMID- 27281107 TI - A label-free colorimetric aptasensor for simple, sensitive and selective detection of Pt (II) based on platinum (II)-oligonucleotide coordination induced gold nanoparticles aggregation. AB - Herein, a gold nanoparticles (AuNPs) based label-free colorimetric aptasensor for simple, sensitive and selective detection of Pt (II) was constructed for the first time. Four bases (G-G mismatch) mismatched streptavidin aptamer (MSAA) was used to protect AuNPs from salt-induced aggregation and recognize Pt (II) specifically. Only in the presence of Pt (II), coordination occurs between G-G bases and Pt (II), leading to the activation of streptavidin aptamer. Streptavidin coated magnetic beads (MBs) were used as separation agent to separate Pt (II)-coordinated MSAA. The residual less amount of MSAA could not efficiently protect AuNPs anymore and aggregation of AuNPs will produce a colorimetric product. With the addition of Pt (II), a pale purple-to-blue color variation could be observed by the naked eye. A detection limit of 150nM and a linear range from 0.6MUM to 12.5MUM for Pt (II) could be achieved without any amplification. PMID- 27281108 TI - A dendrimer-based highly sensitive and selective fluorescence-quenching sensor for Fe(3+) both in solution and as film. AB - A novel fluorescent dendrimer PYTPAG2, with pyrene as the interior core and triphenylamine (TPA) as the exterior periphery, is studied as a fluorescence quenching sensor for iron (sh) ions (Fe(3+)), both in solution and as a film. This dendrimer-based sensor possesses preferential detection of Fe(3+) by a very strong fluorescence quenching not found for other metal ions. The fluorescent detection limits of this PYTPAG2 sensor for Fe(3+) in solution and thin-film are 6.5*10(-7)M and 5.0*10(-7)M, respectively. The possible mechanism of this process is explained by the complexation between the peripheral TPA units of PYTPAG2 and Fe(3+) ions, which may disrupt the fluorescence resonance energy transfer (FRET) from the TPA groups to the pyrene core (intramolecular of PYTPAG2) and results in the fluorescence quenching. Moreover, this striking performance could not be disturbed by pH, the interference with other metal ions, counter anions, or surrounding environment. In addition, biological fluorescence imaging studies of Fe(3+) in living roundworms demonstrate its valuable practical application. PMID- 27281109 TI - Single-Pot Asymmetric Approach toward Enantioenriched Quaternary Stereocenter Containing Alkylidenecyclobutanes. AB - Enantioenriched alkylidenecyclobutanes possessing a quaternary stereogenic center, usually difficult to access, have been synthesized by combining a double boron-homologation and an allylboration through a highly efficient and diastereoselective one-pot process. Starting from commercially available substrates, this protocol represents a simple way of accessing chiral unsaturated four-membered ring systems with excellent stereoisomeric ratios. PMID- 27281111 TI - National Practice Patterns of Antireflux Medication for Chronic Rhinosinusitis. AB - IMPORTANCE: Antireflux medication has been endorsed as a useful adjunctive therapy for chronic rhinosinusitis, but its use remains controversial. OBJECTIVES: To determine whether chronic rhinosinusitis is associated with administration of proton pump inhibitors, histamine2-receptor antagonists, antacids, or prokinetic agents; whether practice patterns vary according to visit setting; and whether those patterns vary according to the presence or absence of potentially confounding conditions. DESIGN, SETTING, AND PARTICIPANTS: A cross sectional analysis was performed of data from January 1, 2005, to December 31, 2010, from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, which included 590 772 observations representing 7 191 711 480 ambulatory care visits. Univariate, multivariate, and stratified analyses were performed from January 1, 2005, to December 31, 2010. EXPOSURES: Chronic rhinosinusitis. MAIN OUTCOMES AND MEASURES: The probability of receiving antireflux medications was the main measured outcome. RESULTS: Of 7 191 711 480 ambulatory care visits, those for chronic rhinosinusitis were not more likely to result in the administration of proton pump inhibitors (odds ratio, 1.00; 95% CI, 0.62-1.63; P = .99) or antacids and prokinetic agents (odds ratio, 1.24; 95% CI, 0.30-5.10; P = .77). In addition, patients with chronic rhinosinusitis were less likely to receive histamine2-receptor antagonists than were those without chronic rhinosinusitis, even when adjusted for age, sex, race/ethnicity, visit setting, other antireflux agents, and presence or absence of gastroesophageal reflux, laryngopharyngeal reflux, or allergy diagnoses (odds ratio, 0.25; 95% CI, 0.12 0.57; P = .001). CONCLUSIONS AND RELEVANCE: National practice patterns observed thus far have not favored the use of proton pump inhibitors, histamine2-receptor antagonists, antacids, or prokinetic agents for chronic rhinosinusitis. PMID- 27281113 TI - A Novel Imaging System Distinguishes Neoplastic from Normal Tissue During Resection of Soft Tissue Sarcomas and Mast Cell Tumors in Dogs. AB - OBJECTIVE: To assess the ability of a novel imaging system designed for intraoperative detection of residual cancer in tumor beds to distinguish neoplastic from normal tissue in dogs undergoing resection of soft tissue sarcoma (STS) and mast cell tumor (MCT). STUDY DESIGN: Non-randomized prospective clinical trial. ANIMALS: 12 dogs with STS and 7 dogs with MCT. METHODS: A fluorescent imaging agent that is activated by proteases in vivo was administered to the dogs 4-6 or 24-26 hours before tumor resection. During surgery, a handheld imaging device was used to measure fluorescence intensity within the cancerous portion of the resected specimen and determine an intensity threshold for subsequent identification of cancer. Selected areas within the resected specimen and tumor bed were then imaged, and biopsies (n=101) were obtained from areas that did or did not have a fluorescence intensity exceeding the threshold. Results of intraoperative fluorescence and histology were compared. RESULTS: The imaging system correctly distinguished cancer from normal tissue in 93/101 biopsies (92%). Using histology as the reference, the sensitivity and specificity of the imaging system for identification of cancer in biopsies were 92% and 92%, respectively. There were 10/19 (53%) dogs which exhibited transient facial erythema soon after injection of the imaging agent which responded to but was not consistently prevented by intravenous diphenhydramine. CONCLUSION: A fluorescence based imaging system designed for intraoperative use can distinguish canine soft tissue sarcoma (STS) and mast cell tumor (MCT) tissue from normal tissue with a high degree of accuracy. The system has potential to assist surgeons in assessing the adequacy of tumor resections during surgery, potentially reducing the risk of local tumor recurrence. Although responsive to antihistamines, the risk of hypersensitivity needs to be considered in light of the potential benefits of this imaging system in dogs. PMID- 27281115 TI - Ionic Liquid-Based Polymer Electrolytes via Surfactant-Assisted Polymerization at the Plasma-Liquid Interface. AB - We first report an innovative method, which we refer to as interfacial liquid plasma polymerization, to chemically cross-link ionic liquids (ILs). By this method, a series of all-solid state, free-standing polymer electrolytes is successfully fabricated where ILs are used as building blocks and ethylene oxide based surfactants are employed as an assisted-cross-linking agent. The thickness of the films is controlled by the plasma exposure time or the ratio of surfactant to ILs. The chemical structure and properties of the polymer electrolyte are characterized by scanning electron microscopy (SEM), Fourier transformation infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) spectroscopy, X ray photoelectron spectroscopy (XPS), differential scanning calorimetry (DSC), and electrochemical impedance spectroscopy (EIS). Importantly, the underlying polymerization mechanism of the cross-linked IL-based polymer electrolyte is studied to show that fluoroborate or halide anions of ILs together with the aid of a small amount of surfactants having ethylene oxide groups are necessary to form cross-linked network structures of the polymer electrolyte. The ionic conductivity of the obtained polymer electrolyte is 2.28 * 10(-3) S.cm(-1), which is a relatively high value for solid polymer electrolytes synthesized at room temperature. This study can serve as a cornerstone for developing all-solid state polymer electrolytes with promising properties for next-generation electrochemical devices. PMID- 27281114 TI - Distribution of Water in Synthetic Calcium Silicate Hydrates. AB - Understanding calcium silicate hydrates (CSHs) is of paramount importance for understanding the behavior of cement materials because they control most of the properties of these man-made materials. The atomic scale water content and structure have a major influence on their properties, as is analogous with clay minerals, and we should assess these. Here, we used a multiple analytical approach to quantify water distribution in CSH samples and to determine the relative proportions of water sorbed on external and internal (interlayer) surfaces. Water vapor isotherms were used to explain the water distribution in the CSH microstructure. As with many layered compounds, CSHs have external and internal (interlayer) surfaces displaying multilayer adsorption of water molecules on external surfaces owing to the hydrophilic surfaces. Interlayer water was also quantified from water vapor isotherm, X-ray diffraction (XRD), and thermal gravimetric analyses (TGA) data, displaying nonreversible swelling/shrinkage behavior in response to drying/rewetting cycles. From this quantification and balance of water distribution, we were able to explain most of the widely dispersed data already published according to the various relative humidity (RH) conditions and measurement techniques. Stoichiometric formulas were proposed for the different CSH samples analyzed (0.6 < Ca/Si < 1.6), considering the interlayer water contribution. PMID- 27281116 TI - Stem Xylem Characterization for Vitis Drought Tolerance. AB - Together with stomatal conductance and root conductivity, the stem water reserve and transport systems could be regulatory mechanisms able to participate in the regulation of the plant water status. Lianas, such as Vitis spp., minimize the trunk support role, and stems have evolved to improve their ability in water transport. In this work, stems of 10 different Vitis species were studied in relation to their expected drought tolerance using reflectance spectroscopy. Spectra were measured before (T0) and after coloration with Sudan IV dye. The T0 spectral signature showed characteristic species features. The partial least squares (PLS) regression and the self-organizing map (SOM) neural network analysis were able to predict the expected drought tolerance score; thus, reflectance spectroscopy was demonstrated to be a useful technique for drought tolerance phenotyping. These methods could be applied for the preliminary selection of new rootstocks/cultivars. Wood composition variation appeared to be correlated with the water stress susceptibility. To clarify this relationship, the attention was focused on the wood hydrophobicity. Sudan IV is a microscopy dye traditionally used to underline suberin, waxes, and, in general, hydrophobic substances. Differences between rough and colored spectra evidenced the absorption band of Sudan IV with a maximum at 539 nm. The coloration intensity was used to develop a hydrophobicity index. The obtained values were correlated with the expected drought tolerance score. Therefore, hydrophobic compounds seem to play an important role in water use efficiency, and an hydrophobic barrier in the xylem tissue appears to be a protective mechanism against water stress. PMID- 27281117 TI - Overview of microprobe analysis in pulmonary pathology. PMID- 27281118 TI - Asbestos content of lung tissue in patients with malignant peritoneal mesothelioma: A study of 42 cases. AB - Lung tissue from 42 peritoneal mesothelioma cases was analyzed by light microscopy and scanning electron microscopy/energy dispersive spectrometry. There were 34 men and 8 women with a mean age of 61 +/- 10 years. Also, 17% of cases had histologically confirmed asbestosis, and 26% had only parietal pleural plaques. The asbestos body count exceeded our normal range in 22 of 42 cases (52%). Cases with asbestos-related pulmonary disease had higher fiber burdens than those without. The vast majority of fibers were commercial amphiboles (amosite with lesser amounts of crocidolite). These findings concur with previously published epidemiological observations. PMID- 27281119 TI - Endogenous pneumoconiosis: Analytical scanning electron microscopic analysis of a case. AB - Pneumoconiosis is often considered a disease of the lung initiated by exposure to dust or other airborne particles, resulting in injury to the lungs. The term "endogenous pneumoconiosis" has been used in the literature to describe the deposition of compounds on the elastic fibers of the lung, usually in the setting of cardiac failure. In the case we present here, the patient aspirated a foreign body resulting in damage to the lung tissue and subsequent deposition of endogenous compounds on the elastic fibers of the pulmonary parenchyma and vasculature. We determined the composition of this mineral and mapped the distribution of elements using a combination of backscattered electron microscopy and energy dispersive spectrometry. PMID- 27281120 TI - Dysbindin as a novel biomarker for pancreatic ductal adenocarcinoma identified by proteomic profiling. AB - Pancreatic adenocarcinoma (PDAC) is known to have a poor prognosis partly because of lack of effective biomarkers. In the test set, we investigated dysbindin (DTNBP1) as a potential biomarker for PDAC by comparing preoperative and postoperative serum mass spectrometry (MS) proteomic profilings. Of the included 50 PDAC patients, 42 (positivity of 84.0%) detected a lower MS peak in postoperative serums than preoperative ones which was then identified as dysbindin. In the verification set, receiver operating characteristics (ROC) were used to assess diagnostic efficiency. 550 participants were included in the verification set [250 with PDAC, 80 with benign biliary obstruction (BBO), 70 with chronic pancreatitis (CP) and 150 healthy donors (HD)]. Dysbindin was increased in PDAC patient sera than in all controls. ROC curves revealed the optimum diagnostic cutoff for dysbindin was 699.16 pg/ml [area under curve (AUC) 0.849 (95% CI 0.812-0.885), sensitivity 81.9% and specificity 84.7%]. Raised concentration of dysbindin in sera could differentiate PDAC from BBO, CP and HD. Moreover, dysbindin maintained its diagnostic accuracy for PDAC patients who were CA19-9 negative [AUC 0.875 (95% CI 0.804-0.945), sensitivity 83.0%, specificity 89.0%] and for patients with benign biliary obstruction [AUC 0.849 (95% CI 0.803 0.894), sensitivity 82.3%, specificity 84.0%].Our discovery of dysbindin may complement measurement of CA19-9 in the diagnosis of PDAC and help to discriminate PDAC from other pancreatic diseases or begin biliary obstruction. PMID- 27281121 TI - Complex Polarity: Building Multicellular Tissues Through Apical Membrane Traffic. AB - The formation of distinct subdomains of the cell surface is crucial for multicellular organism development. The most striking example of this is apical basal polarization. What is much less appreciated is that underpinning an asymmetric cell surface is an equally dramatic intracellular endosome rearrangement. Here, we review the interplay between classical cell polarity proteins and membrane trafficking pathways, and discuss how this marriage gives rise to cell polarization. We focus on those mechanisms that regulate apical polarization, as this is providing a number of insights into how membrane traffic and polarity are regulated at the tissue level. PMID- 27281122 TI - Bromine-rich Zinc Bromides: Zn6Br12(18-crown-6)2*(Br2)5, Zn4Br8(18-crown 6)2*(Br2)3, and Zn6Br12(18-crown-6)2*(Br2)2. AB - The bromine-rich zinc bromides Zn6Br12(18-crown-6)2*(Br2)5 (1), Zn4Br8(18-crown 6)2*(Br2)3 (2), and Zn6Br12(18-crown-6)2*(Br2)2 (3) are prepared by reaction of ZnBr2, 18-crown-6, and elemental bromine in the ionic liquid [MeBu3N][N(Tf)2] (N(Tf)2 = bis(trifluoromethylsulfonyl)amide). Zn6Br12(18-crown-6)2*(Br2)5 (1) is formed instantaneously by the reaction. Even at room temperature, compound 1 releases bromine, which was confirmed by thermogravimetry (TG) and mass spectrometry (MS). The release of Br2 can also be directly followed by the color and density of the title compounds. With controlled conditions (2 weeks, 25 degrees C, absence of excess Br2) Zn6Br12(18-crown-6)2*(Br2)5 (1) slowly releases bromine with conconcurrent generation of Zn4Br8(18-crown-6)2*(Br2)3 (2) (in ionic liquid) and Zn6Br12(18-crown-6)2*(Br2)2 (3) (in inert oil). All bromine-rich zinc bromides contain voluminous uncharged (e.g., Zn3Br6(18-crown-6), Zn2Br4(18-crown 6)) or ionic (e.g., [Zn2Br3(18-crown-6)](+), [(Zn2Br6)*(Br2)2](2-)) building units with dibromine molecules between the Zn oligomers and partially interconnecting the Zn-containing building units. Due to the structural similarity, the bromine release is possible via crystal-to-crystal transformation with retention of the crystal shape. PMID- 27281123 TI - T cell cytokine responses to stimulation with Ureaplasma parvum in pregnancy. AB - Ureaplasma spp. are a common vaginal microorganism causally linked to inflammation-driven preterm birth (PTB). The nature of the immune response to Ureaplasma spp. may influence PTB risk. This study sought to define maternal T cell cytokine responses to in vitro stimulation with Ureaplasma parvum serovar 3 (UpSV3) in vaginally colonised (UP+) and non-colonised (UP-) pregnant women. Whole blood flow cytometry demonstrated an increase (p=0.027) in the baseline frequency of IFNgamma-positive CD3(+)CD4(-)(CD8(+)) T cells in UP+ women. UpSV3 stimulation resulted in a significant and specific increase (p=0.001) in the frequency of IFNgamma-positive CD3(+)CD4(-)(CD8(+)) T cells, regardless of vaginal colonisation status. UpSV3 stimulation also increased the frequency of IFNgamma-positive CD3(+)CD4(+) T cells, particularly in the UP+ group (p=0.003). This is the first published study to examine T cell responses to Ureaplasma spp. EXPOSURE: Future appropriately-powered studies are needed to assess whether insufficient priming or a loss of tolerance to Ureaplasma spp. is occurring in UP+ women at risk of PTB. PMID- 27281124 TI - Highly Efficient Blue Phosphorescent Organic Light-Emitting Diodes Employing a Host Material with Small Bandgap. AB - Blue phosphorescent organic light-emitting diode (PhOLED) with a high maximum external quantum efficiency (EQE) of 26.6% was achieved using a new material, 2,8 bis(9,9-dimethylacridin-10(9H)-yl)dibenzo[b,d]furan (DBF-DMS) with a small bandgap, as the host. The device with DBF-DMS showed improved performance compared with that with 1,3-di-9-carbazolylbenzene, which is ascribed to the enhancement in carrier injection and transporting abilities and material stability of DBF-DMS. A lifetime of more than 100 h (time to 50% of the initial luminance, 1000 cd/m(2) with an EQE of 19.6%) in the other DBF-DMS-based device is obtained by further utilizing better device structure. This is a report indicating that host material with a small bandgap like DBF-DMS can be successfully utilized toward blue PhOLEDs with high performance. PMID- 27281125 TI - Duration of Untreated Psychosis in Chinese and Mauritian: Impact of Clinical Characteristics and Patients' and Families' Perspectives on Psychosis. AB - BACKGROUND: Duration of untreated psychosis (DUP) is a potentially modifiable prognostic factor of course and prognosis of psychiatric disorders. Few studies have demonstrated that different cultural backgrounds or perspectives on psychosis may be important factors to the DUP. This study attempted to explore whether the DUP was different in Chinese and Mauritians and to clarify potential influencing factors to a long DUP (>3 months). METHODS: 200 patients from China and 100 patients from Mauritius were enrolled in the study. Their respective family members were also recruited. Demographic and clinical characteristics were collected, and the Internalized Stigma of Mental Illness (ISMI) scale was adapted to measure the stigma in all subjects. Binary logistic regression analysis was used to find the potential influencing factors to the long DUP. RESULTS: 35.3% of the enrolled patients had a long DUP. No significant difference was found in frequency of long DUP between the two countries. Chinese patients had relatively less perceptions of stigma. Furthermore, Chinese patients with a long DUP had more perception of breakup due to mental illness (OR = 2.22, p = 0.04) and more families' perception of the patient being disinherited due to mental illness (OR = 6.47, p = 0.01). Mauritian patients with a long DUP were less likely to have high monthly income (OR = 0.12, p<0.01), while they had less patients' awareness of mental illness (OR = 0.31, p<0.05) and less families' awareness of mental illness (OR = 0.14, p<0.01). CONCLUSION: The results of this study underlined the importance of DUP in economic conditions, racial and sociocultural factors, and public awareness on psychosis in developing countries. PMID- 27281126 TI - Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder. AB - BACKGROUND: Selective serotonin reuptake inhibitors (SSRI) are established first line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. METHODS: We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. RESULTS: While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. CONCLUSIONS: Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients. PMID- 27281128 TI - Critical Review Upon the Role and Potential of Fluorescence and Near-Infrared Imaging and Absorption Spectroscopy in Cancer Related Cells, Serum, Saliva, Urine and Tissue Analysis. AB - During the last years, non-invasive or minimally invasive diagnostic tools in cancer diagnostics have become more important. Many fluorescence spectroscopic methodologies have been established for nearly all different kinds of cancer. The reason therefore is its high sensitivity, low amount of sample required, short testing time, and the suitability for in situ testing. The potential influence factors for cancer diagnostics and the subsequent suitability of the method to different applications are well described. Near-Infrared spectroscopy (NIRS) is based on differences of endogenous chromophores between cancer and normal tissues using either oxyhaemoglobin or deoxy-haemoglobin, lipid or water bands, or a combination of two or more of these diagnostic markers. These marker bands are known to provide the fundamental for the diagnosis of several cancers and the spectroscopic setup can be applied for the analysis of cells, urine and tissue. For the preparation of this review the literature published during the last fifteen years has been taken into consideration. It will provide an overview on the importance of the fluorescence and NIRS tools in cancer analysis giving hints about how these techniques can play a crucial role in cancer diagnosis, treatment decisions and therapy. The two techniques, fluorescence and near-infrared spectroscopy (NIRS) are faced to each other and individual advantages and/or drawbacks are discussed. Finally, it will be taken into consideration; how the synergistic combination of different approaches can give additional information related to development and progression stages of cancer. PMID- 27281127 TI - Extracellular Matrix in Atherosclerosis: Hyaluronan and Proteoglycans Insights. AB - BACKGROUND: Atherosclerosis, a chronic inflammatory disease of the blood vessel wall, is the most common cause of cardiovascular pathologies. Hyaluronan, the major polysaccharide involved in this process, plays a pivotal role acting as a modulator of all inflammatory stages, affecting the behavior of both endothelial and smooth muscle cells. OBJECTIVE: The inflammatory condition is the main reason of the increased deposition of extracellular matrix, that in turn, traps lipoproteins and inflammatory/growth factors from the circulation within the vessel wall and thicken the arterial wall. Therefore, this chronic condition that continuously affects the arterial walls in a specific area causes a severe remodeling of the tissue architecture and a drastic change in the resident cell behavior. METHODS: Because of the great complexity of the extracellular matrix in the arterial wall, we investigate the modification in the different layers of the vessels with a particular attention to hyaluronan and proteoglycans and to the events that affects their normal turnover. RESULTS: Hyaluronan, the major polysaccharide involved in this process, plays a pivotal role acting as a modulator of all inflammatory stages, affecting the behavior of both endothelial and smooth muscle cells. Moreover, glycosaminoglycans and proteoglycans had been shown to change during the lesion progression, and to possess the chemical features essential for lipid retention, immune system activation, smooth cells proliferation and macrophages recruitment. CONCLUSION: The ECM characteristics should be investigated in order to understand their prevention potentials as well as their negative impact on the onset of the disease. PMID- 27281129 TI - Targeting Stim and Orai Proteins as an Alternative Approach in Anticancer Therapy. AB - An increase in intracellular Ca2+ concentration plays a key role in the establishment of many cancer hallmarks, including aberrant proliferation, migration, invasion, resistance to apoptosis and angiogenesis. The dysregulation of Ca2+ entry is one of the most subtle mechanisms by which cancer cells overwhelm their normal counterparts and gain the adaptive advantages that result in tumour growth, vascularisation and dissemination throughout the organism. Both constitutive and agonist-induced Ca2+ influx may be mediated by store-dependent as well as store-independent Ca2+ entry routes. A growing body of evidences have shown that different isoforms of Stromal Interaction Molecules (Stim1) and Orai proteins, i.e. Stim1, Stim2, Orai1 and Orai3, underlie both pathways in cancer cells. The alteration in either the expression or the activity of Stim and Orai proteins has been linked to the onset and maintenance of tumour phenotype in many solid malignancies, including prostate, breast, kidney, esophageal, skin, brain, colorectal, lung and liver cancers. Herein, we survey the existing data in support of Stim and Orai involvement in tumourigenesis and provide the rationale to target them in cancer patients. Besides, we summarize the most recent advances in the identification of novel pharmacological tools that could be successfully used in clinical therapy. PMID- 27281130 TI - Myeloperoxidase as a Target for the Treatment of Inflammatory Syndromes: Mechanisms and Structure Activity Relationships of Inhibitors. AB - Inflammation is an initial response of the body to a harmful stimuli and it is achieved by the increased movement of leukocytes (especially granulocytes) from blood into injured tissues. It is required for healing wounds and infections. Despite their indispensable role in microbial killing, the inflammation reactions may also cause diseases to a host such as hay fever, atherosclerosis, and rheumatoid arthritis. The enzymes and oxidizing species released during the inflammatory process can cause damages to the host tissues which lead to inflammatory syndromes. The role of myeloperoxidase (MPO) in the inflammatory reactions is well documented. It contributes in killing the pathogens but it is also implicated in several inflammatory syndromes such as Parkinson's disease, Alzheimer's disease and atherosclerosis. Thus, this enzyme has attracted more attention of the scientists and it has become a target for drug designing. In the last decade, several reversible and irreversible MPO inhibitors were identified as very high potent inhibitors such as fluoroalkylindole, aromatic hydroxamic acid, thioxanthine and benzoic acid hydrazide derivatives. In this review, we tried to illustrate the MPO inhibitors and highlight their structure activity relationship (SAR). In this paper we also discussed the mechanism of the inhibitory effect of the most potent compounds. PMID- 27281132 TI - Recent Trends of Biocompatible and Biodegradable Nanoparticles in Drug Delivery: A Review. AB - A vast amount of research on nanoparticles has been conducted in recent years with versatile applications in the field of drug delivery systems. Nanoparticles are designed as a carrier molecule to deliver drugs in a sustained and stimuli response manner. Recent advances in nanotechnology have led to the development of long circulating nanoparticles with high encapsulation efficiency. This article focuses on the properties such as biocompatibility and biodegradability, which are considered as essential criteria for nanoparticles to be successfully used as a carrier molecule in drug delivery systems. Physicochemical characterization of the nanoparticles such as size and size distribution, surface morphology, zeta potential and surface chemistry has a significant role in the successful formulation and applications in drug delivery systems. Mostly, the size and surface characteristics of nanoparticles enable enhanced intracellular accumulation in tumor cells through passive targeting mechanisms and rapid development of nanoengineering, and aid towards attaining active targeting delivery by co-functionalization of nanoparticles using appropriate targeting ligands. This article reviews the recent progress and development of employing different biocompatible and biodegradable nanoparticles in drug delivery systems. It also briefly recaps the important methods available to evaluate its biocompatibility, the mechanism of biodegradability and clearance properties of NPs. PMID- 27281133 TI - Ensemble of Pinanones from the Permanganate Oxidation of Myrtenal. AB - The buffered permanganate oxidation of (-)-myternal, a member of the pinene family, provides the alpha-hydroxyketone (-)-(1R,3S,5R)-3-hydroxy-6,6 dimethylbicyclo[3.1.1]heptan-2-one in preparative yield (65% on a multigram scale). This alpha-hydroxyketone is oxidized, in a second reaction, to the alpha,beta-diketone (1R,5R)-6,6-dimethylbicyclo[3.1.1]heptane-2,3-dione ("PinDione"). As both oxidations are fast, simple, safe, inexpensive, good yielding, and multigram scalable, these transformations are a preparative expansion of the pinane family. PMID- 27281134 TI - Use of Palliative Chemo- and Radiotherapy at the End of Life in Patients With Cancer: A Retrospective Cohort Study. AB - BACKGROUND: Administration of chemotherapy and radiotherapy near the end of life is a frequently discussed issue nowadays. We have evaluated the factors associated with the use of chemotherapy and radiotherapy at the end of life among terminally ill patients in China. METHODS: This study included the data from patients who had died from advanced cancer who underwent palliative chemotherapy and radiotherapy between January 2007 and December 2013 at the Department of Palliative Care of Fudan University, Shanghai Cancer Center. Data were collected from hospital medical records. Univariate and multivariate analyses were conducted to identify the factors independently associated with the use of chemo- and radiotherapy. RESULTS: Among the 410 patients included (median age, 68 years; range, 18-93; 53% males), 47 (11.5%) underwent palliative chemotherapy and 28 (6.8%) underwent radiotherapy in the last 30 days. Age <65 years (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.06-2.88), performance status <3 (OR: 3.95; 95% CI: 1.56-5.07), and cardiopulmonary resuscitation (OR: 4.09, 95% CI: 2.66-5.34) were independently associated with the use of chemotherapy. Performance status <3 (OR: 4.06, 95% CI: 2.17-5.83) and cardiopulmonary resuscitation (OR: 5.28, 95% CI: 3.77-7.21) were independently associated with the use of radiotherapy. CONCLUSION: The findings indicate that younger patients with a lower performance status who do not have complications are more likely to opt for chemo- or radiotherapy. Further, the use of palliative chemo- and radiotherapy should be considered carefully in terminally ill patients with cancer, as they seem to indicate a higher risk of cardiovascular complications requiring resuscitation. PMID- 27281135 TI - Fractal Nature of Food Materials. AB - Through the concept of fractals, the new non-integer dimensional world is introduced. Experimental results to show this new world are taken from the author and his colleagues' own works. A few words are given also to the scaling law in the "Critical phenomena" in relation to sol-gel transition, and Chaos, both of which are closely related to the fractal. PMID- 27281136 TI - Conformational Analysis of Abscisic Acid Analogs Produced by Cercospora cruenta. AB - The conformation of hydroxy-gamma-ionylideneacetic acids produced by Cercospora cruenta was examined by 'H-NMR analysis. (1)H-(1)H COSY and NOE data indicated that (2Z,4E,1'R,4'#)-4'-hydroxy-(gamma)- ionylideneacetic acid has a cyclohexane ring of chair form furnishing a hydroxyl group and a 2,4-pentadienoic acid moiety, each with equatorial orientation, while (2Z,4E,1'S,3'S)-3'-hydroxy-gamma ionylideneacetic acid has a flexible twisted-boat form of cyclohexane ring. It is suggested that the structure of another (2Z,4E,1'S,4'R)-isomer of 4'-hydroxy gamma-ionylideneacetic acid with an equatorial hydrogen at the l'-position is the key for further oxygenation to abscisic acid. PMID- 27281131 TI - Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain. AB - The microglia, once thought only to be supporting cells of the central nervous system (CNS), are now recognized to play essential roles in many pathologies. Many studies within the last decades indicated that the neuro-immune interaction underlies the generation and maintenance of neuropathic pain. Through a large number of receptors and signaling pathways, the microglial cells communicate with neurons, astrocytes and other cells, including those of the immune system. A disturbance or loss of CNS homeostasis causes rapid responses of the microglia, which undergo a multistage activation process. The activated microglia change their cell shapes and gene expression profiles, which induce proliferation, migration, and the production of pro- or antinociceptive factors. The cells release a large number of mediators that can act in a manner detrimental or beneficial to the surrounding cells and can indirectly alter the nociceptive signals. This review discusses the most important microglial intracellular signaling cascades (MAPKs, NF-kB, JAK/STAT, PI3K/Akt) that are essential for neuropathic pain development and maintenance. Our objective was to identify new molecular targets that may result in the development of powerful tools to control the signaling associated with neuropathic pain. PMID- 27281137 TI - Synthesis and Biological Activities of Substituted 4,4,4-Trifluoro-3-(indoIe-3 )butyric Acids, Novel Fluorinated Plant Growth Regulators. AB - Substituted 4,4,4-trifluoro-3-(indole-3-)butyric acids (TFIBAs), novel fluorinated plant growth regulators, were easily synthesized from substituted 2,2,2-trifluoro-l-(indole-3-)ethanols. The synthetic substituted TFIBAs showed marked root growth-promoting activity toward Chinese cabbage, lettuce, and rice plants. 5-MeO-2-Me-TFIBA (2d) had especially strong promoting activity toward Chinese cabbage, while 5-Me- TFIBA (2b) markedly promoted the root growth of all three plants. The promoting activity of TFIBAs halogenated at the 5-position in the indole nucleus of the molecule (5-Br- and 5-C1-TFIBA (2e and 2g)) was also greater than the activity of TFIBA, the original non-substituted compound. 5-N02 TFIBA (2h) with a strong electron-withdrawing group showed only very weak root growth-promoting activity. PMID- 27281138 TI - Purification and Characterization of Ethyl 2-Methyl-3-oxobutanoate Reductase from Klebsiella pneumoniae IF03319. AB - An enzyme that catalyzes a reduction of ethyl 2-methyl-3-oxobutanoate (1) to ethyl (2R,3S) 3-hydroxy- 2-methylbutanoate was found in Klebsiella pneumoniae IFO 3319 cells. The enzyme was isolated from the cells and purified 250-fold by ammonium sulfate fractionation, ion exchange chromatography, affinity chromatography, and gel filtration. The purified enzyme was found to be a monomer protein with a molecular weight of approximately 31,000 and an isoelectric point of 6.2. It was NADPH-dependent and had maximum activity at pH 7.0 and 45 degrees C for the reduction and at pH 10.0 and 45 degrees C for oxidation. The Km's at pH 7.0 were 5.6 mM for 1 and 12.5 mM for benzyl 2-methyl-3-oxobutanoate, respectively. Esters of 2-oxocycloalkane carboxylic acids as well as esters of 2 methyl-3-oxobutanoic acid served as substrates, and the corresponding reduced products were obtained with high stereoselectivity. PMID- 27281139 TI - Selective Oxidation of 2-Methylnaphthalene to 2-Methyl-l-naphthol by Rhodococcus sp. M192. AB - About 6000 isolates of microorganisms assimilating methylketones (C3-C6) were tested for their selective oxidation of 2-methylnaphthalene to 2-methyl-1 naphthol. Strain M192 was the highest 2-methyl-1-naphthol producer and was classified as the genus Rhodococcus. The optimal conditions for the site-specific oxidation were studied using resting Rhodococcus sp. M192. The 2-methyl-1 naphthol productivity was specifically increased using methylethylketone as a carbon source, 1-propanol as a solvent to dissolve the substrate, and ethylxanthate or diethyldithiocarbamate as an inhibitor of 2-naphthoic acid (side product) production. In the presence of these compounds, 2-methylnaphthalene was specifically oxidized at the 1-position without the conversion to 2-naphthoic acid. The productivity of 2-methyl-1-naphthol was about 90 MUM from 1 mM 2 methylnaphthalene. PMID- 27281140 TI - Mold Pectinase Modified with Dialdehyde Derivatives of Dextran and Cellulose. AB - Chemical modification of mold pectinase with dextran- and cellulose-dialdehydes was examined to improve the enzyme characteristics. The modified pectinase with dextran-dialdehyde retained about 50% of the original activity, and more than 80% of the total amino groups were modified. HPLC gel filtration analysis showed an increase in molecular weight of the reaction product. Reaction with cellulose dialdehyde provided an immobilized form of pectinase. The immobilized pectinase was resistant to both acidic and alkaline pHs, and also acquired heat stability at 60 degrees C. The optimum pH of the modified enzyme shifted from pH 4.5 to 5.0 5.5, and this enzyme had higher activity at neutral pH regions than the native enzyme. A rather low recovery of immobilized enzyme (14.5%) should be improved by the combination with various methods hitherto established. PMID- 27281141 TI - Methoxypyrazine Content of Japanese Red Wines. AB - Three 2-methoxy-3-alkylpyrazines (MPs) in Japanese red wine and grape samples were determined by GC-EIMS, using 2-methyl-3-n-propylpyrazine as an internal standard. MPs in the Cabernet Sauvignon red wines were derived not only from the pulp but also from other parts of the grape berries. All of the Cabernet Sauvignon red wines made annually from 1975 to 1994 contained 2-methoxy-3 isobutylpyrazine (isobutylMP), although those made from well-ripened grapes had a low isobutylMP level. It is suggested that the climatic conditions of September might effect the isobutylMP level of Cabernet Sauvignon grapes and red wines. The mean isobutylMP level of Cabernet Sauvignon, Cabernet Franc, and Merlot Japanese commercial red wines was significantly higher than the mean isobutylMP level of Muscat Bailey A and Zweigeltrebe. PMID- 27281142 TI - Kinetic Study of the Active Site Structure of beta-Amylase from Bacillus cereus var. mycoides. AB - The subsite affinities of the active site of beta-amylase from Bacillus cereus var. mycoides were evaluated based on Hiromi's theory, using (14)C-radiolabeled maltooligosaccharides as substrate. It was estimated that the active site consisted of six subsites, and all subsite affinities could be evaluated. The active site had a common subsite arrangement with those of beta -amylases from soybean and wheat bran. The intrinsic breakdown rate constant of alpha-1,4 glucosidic linkage (kint) was five to seven times as large as those of the other enzymes.From the pH dependence of log[k0/Km], pK values of two functional ionizable groups were pK1 =4.0 and pK2 = 8.4. The pK values were 0.5-0.6 units for pK1 and 0.2-0.3 units for pK2 larger than those of the other enzymes. For the affinity-labeling of this enzyme by 2, 3 epoxypropyl alpha-D-glucopyranoside (alpha-EPG), the binding affinity of alpha-EPG was 1-1.6kcal/mol larger than those of the other beta-amylases. PMID- 27281143 TI - Purification and Characterization of a Thermostable Trehalose Synthase from Thermus aquaticus. AB - Thermostable trehalose synthase, which catalyzes the conversion of maltose into trehalose by intramolecular transglucosylation, was purified from a cell-free extract of the thermophilic bacterium Thermus aquaticus ATCC 33923 to an electrophoretically homogeneity by successive column chromatographies. The purified enzyme had a molecular weight of 105,000 by SDS-polyacrylamide gel electrophoresis and a pI of 4.6 by gel isoelectrofocusing. The N-terminal amino acid of the enzyme was methionine. The optimum pH and temperature were pH 6.5 and 65 degrees C, respectively. The enzyme was stable from pH 5.5 to 9.5 and up to 80 degrees C for 60min. The trehalose synthase from Thermus aquaticus is more thermoactive and thermostable than that from Pimelobacter sp. R48. The yield of trehalose from maltose by the enzyme was independent of the substrate concentration, and tended to increase at lower temperatures. The maximum yield of trehalose from maltose by the enzyme reached 80-82% at 30-40 degrees C. The activity was inhibited by Cu(2+) , Hg(2+), Zn(2+), and Tris. PMID- 27281144 TI - Measurement of L-Malate Using Immobilized Enzyme Reactors: Comparison of Results Obtained with Four Different Enzymatic Systems. AB - For the measurement of malate by an enzyme sensor, we did a comparative study using malate dehydrogenase (MDH) alone, MDH and glutamate oxaloacetate transaminase (GOT) together, a malic enzyme (ME) that requires NADP as a cofactor, and MDH and NADH oxidase together. With respect to the response of each reactor to 0.5 mM L-malate, the systems using ME alone and MDH plus NADH oxidase gave high values. The ranges of measurements were 0.05-1.00 mM (MDH alone), 0.01 0.05 mM (MDH plus GOT), 0.01-0.50 mM (ME alone) and 0.02-1.00 mM (MDH plus NADH oxidase). In the system with MDH alone, however, reducing sugars in the sample interfered with measurements and it was impossible to use this system for practical analysis of fruit samples. By contrast, the systems using ME alone or MDH plus NADH oxidase were unaffected by the presence of reducing sugars and were suitable for analysis of samples. Thus, the MDH-NADH oxidase system is recommended for practical analyses of samples. PMID- 27281145 TI - Effect of Uniconazole and Gibberellin on the Flowering of Pharbitis nil. AB - The role of endogenous gibberellin (GA) in the flowering of the short-day plant, Pharbitis nil, was investigated by using uniconazole, which is a specific inhibitor of GA biosynthesis. Both the endogenous GA level and flowering response decreased with increasing concentration of uniconazole applied via the roots. The strongest inhibition of flowering was observed when uniconazole was applied one day before a 15-h dark treatment. The inhibition by uniconazole was overcome by an application of GAs to the plumules, the order of effectiveness of the endogenous GAs in P. nil being GA1 ?GA20>GA19?GA44>GA53"GAH. This is the first report of the correlation between the endogenous GA level and flowering response in P. nil. It was found that endogenous GAs were required for the flowering of P. nil during or just after the dark period. PMID- 27281146 TI - Inhibiting Effects of Lunularic Acid Analogs on the Growth of Liverwort, Watercress, and Timothy Grass. AB - A number of analogs of lunularic acid varying in the number of methylene carbons between the two benzene rings and in the substituents on their rings were prepared, and their effects on the growth of liverwort gemmaling, watercress, and timothy grass were investigated. Almost all the analogs tested were more inhibitory than lunularic acid, and a correlation between the structure and activity was observed. The differences in the growth-inhibition activity of analogs between higher and lower plants are also discussed. PMID- 27281147 TI - A Tentative Measurement of Brown Pigments in Various Processed Foods. AB - A tentative method for measuring brown pigment in food was proposed and applied to 25 items of commercial browned foods. The principle was based on the assumption that any brown pigment with general absorption in the visible wave length spectrum is quantitatively equivalent to melanoidin prepared from a model system of the Maillard reaction. The spectral curve for general absorption was represented by the equation dE/dlambda=-kE (E, absorbance; lambda = wave length; k = constant > 0), of which the value k w as found to correlate with the molecular weight and the molar extinction coefficient and to serve as an empirical parameter for the measurement of brown substances in different foods. PMID- 27281148 TI - Inhibiting Effect of Browned Processed Foods on Trypsin. AB - Inhibition of proteases was examined in browned foods including soy pastes, soy sauces, fish sauce, sauces, teas, coffees, and others in association with melanoidin, a Maillard product, which had been found to be a potent inhibitor of trypsin. Most of the foods were effective in restraining trypsin activity based on hydrolysis of N-alpha-benzoyl-DL-arginine-p-nitroanilide, while being ineffective on chymotrypsin except for black tea and cola. Especially, teas were noted for their strong inhibitory effect on trypsin. The color intensity of the foods in terms of optical density at 400 nm appeared not to correlate with the extent of inhibition except for soy sauces. PMID- 27281149 TI - Conversion of Naphthoates to cis-Dihydrodiols by Naphthalenesulfonate assimilating Pseudomonas sp. TA-2. AB - A naphthalenesulfonate-assimilating bacterium, Pseudomonas sp. TA-2, was found to convert 2-naphthoate to cis-1,2-dihydroxv-1,2-dihydronaphthalene-2-carboxylate (DDN2C) and cis-l,2-dihydroxy-l,2-dihydronaphthalene-3-carboxylate (DDN3C), and converted 1-naphthoate to as-l,2-dihydroxy-l,2-dihydronaphthalene-l-carboxylate (DDN1C). It was suggested that conversion of naphthoates was done by a dioxvgenase with relaxed regioselectivity. PMID- 27281150 TI - Improved Purification and Spectroscopic Properties of Squash Glutamate Decarboxylase. AB - Squash glutamate decarboxylase was purified by DEAE-Cellulose batchwise followed by Blue-Sepharose, Cellulofine GCL-2000, and Toyopearl HW-55F column chromatography. The purified glutamate decarboxylase had a high specific activity (95.0 u/mg). The absorption spectrum of glutamate decarboxylase had an absorption maximum at 420 nm in the range 300-500 nm. A pH change from 5.3 to 7.8 was accompanied by a decrease in absorbancy at 420 nm. One mole of glutamate decarboxylase contained 3.8 and 1.3 mol of pyridoxal 5'-phosphate at pH 5.8 and pH 7.8, respectively. PMID- 27281151 TI - Duration of Treatment of Carrot Hypocotyl Explants with 2,4-Dichlorophenoxyacetic Acid for Direct Somatic Embryogenesis. AB - The relationship between the concentration of 2,4-dichlorophe- noxyacetic acid (2,4-D) and the duration of treatment with 2,4-D on direct somatic embryogenesis from carrot hypocotyl explants was examined. Elevated concentrations of 2,4-D (up to 100 mg/ liter) reduced the duration of pretreatment required for successful embryogenesis. PMID- 27281152 TI - Effects of Uniconazole-P on Abscission and Endogenous ABA, IAA, and GA-like Substances Levels of Satsuma Mandarin Fruitlet. AB - Uniconazole-P, a gibberellin (GA) biosynthesis inhibitor, did not affect growth of mandarin fruitlets definitely but stimulated abscission markedly. Endogenous abscisic acid concentration in fruitlets treated with uniconazole-P was about 4 fold higher compared with the control. Endogenous indole-3-acetic acid and total GAs levels also changed. The relationships between these changes in endogenous hormone levels and fruit abscission were discussed. PMID- 27281153 TI - Easy Preparation Method for 2-Thioxopyrrolidine Derivatives Including 3-Hydroxy- methylene-2-thioxopyrrolidine, an Antimicrobial Degradation Product of Radish Pungent Principle, via (E,Z)-4-Ylethoxy-3-butenyl Isothiocyanate. AB - An easy preparation method was developed for 3-hydroxymethylene-2 thioxopyrrolidine (TPC), an antimicrobial degradation product of radish pungent principle. The key intermediate, 4- methoxy-3-butenyl-isothiocyanate (MBI), which was prepared from 3-cyanopropionaldehyde dimethyl acetal in 3 reaction steps, was easily converted to TPC in acidic (pH 3.0-4.0) aqueous media. In methanol or ethanol with a few drops of acetic acid, MBI afforded corresponding 3 (alpha,alpha-dialkoxy)methyl-2-thioxopyrrolidines as the major products. PMID- 27281154 TI - A Facile Synthesis of (R)-3-Amino-4-phenylbutyric Acid from L-Aspartic Acid. AB - A practical synthesis of (R)-3-amino-4-phenylbutyric acid 1, based on Friedel Crafts acylation with the alpha-aminocarboxyl group of L-aspartic acid retaining its original alpha-carbon chirality, is described. PMID- 27281155 TI - Reaction Mechanism of a New Glycosyltrehalose-producing Enzyme Isolated from the Hyperthermophilic Archaeum, Sulfolobus solfataricus KM1. AB - An amylolytic activity, which converts soluble starch to alpha,alpha-trehalose (trehalose), was found in the cell homogenate of the hyperthermophilic, acidophilic archaeum Sulfolobus solfataricus KM1. Two enzymes, a glycosyltransferase and an amylase, which are essential for this activity, were purified to homogeneity. A glycosyltransferase catalyzed the conversion of maltooligosaccharides to glycosyltrehaloses. Based on a detailed analysis of the reaction products, kinetic parameters, and an experiment using (3)H-labeled substrates, it was verified that glycosyltransferase transferred an oligomer segment of maltooligosaccharide to the Cl-OH position of glucose, located at the reducing end of the maltooligosaccharide, to produce a glycosyltrehalose having an alpha-1,1 linkage. The reaction appears to be intramolecular. Nine strains of the Sulfolobaceae family were found to have glycosyltransferases. PMID- 27281156 TI - Reaction Mechanism of a New Glycosyltrehalose-hydrolyzing Enzyme Isolated from the Hyperthermophilic Archaeum, Sulfolobus solfataricus KM1. AB - Amylolytic activity, which converts soluble starch to alpha,alpha-trehalose (trehalose), was found in the cell homogenate of the hyperthermophilic acidophilic archaeum, Sulfolobus solfataricus KM1. Two enzymes, a glycosyltransferase and an alpha-amylase, which were essential for this activity were identified. The alpha-amylase was purified to homogeneity on SDS-PAGE. The alpha-amylase catalyzed the hydrolysis of glycosyltrehaloses to trehalose. Analysis of the reaction products, kinetic parameters, and experimental findings using (3)H-labeIed substrates indicated that the alpha-amylase hydrolyzed only the alpha-1,4 glucosidic linkage adjacent to the trehalose unit of the glycosyltrehaloses. Six strains of the Sulfolobaceae family examined were observed to have the glycosyltrehalose-hydrolyzing enzyme, the alpha-amylase. PMID- 27281157 TI - Estimate of Unmet Need for Cleft Lip and/or Palate Surgery in India. AB - IMPORTANCE: The unmet need for cleft lip and/or palate (CL/P) care in India is significant. However, estimates required for CL/P care program planning are lacking. OBJECTIVE: To estimate the unmet need for CL/P surgery in India at the state level. DESIGN, SETTING, AND PARTICIPANTS: To determine the proportion of individuals with CL/P who presented for care in India, data were used from patients who received care at Operation Smile programs in 12 low- and middle income countries from June 1, 2013, to May 31, 2014. The resulting model describes the prevalent unmet need for cleft surgery in India by state and includes patients older than the surgery target ages of 1 and 2 years for cleft lip and cleft palate repair, respectively. Next, the total number of unrepaired CL/P cases in each state was estimated using state-level economic and health system indicators. MAIN OUTCOMES AND MEASURES: Prevalent unmet need for CL/P repair. RESULTS: In the 28 states with available data, an estimated 72 637 cases of unrepaired CL/P (uncertainty interval, 58 644-97 870 cases) were detected. The percentage of individuals with unrepaired CL/P who were older than the respective target ages ranged from 37.0% (95% CI, 30.6%-43.8%) in Goa to 65.8% (95% CI, 60.3%-70.9%) in Bihar (median, 57.9%; interquartile range, 52.6%-63.4%). The rate of unrepaired CL/Ps ranged from less than 3.5 per 100 000 population in Kerala and Goa to 10.9 per 100 000 population in Bihar (median rate, 5.9 [interquartile range, 4.6-7.3] per 100 000 population). CONCLUSIONS AND RELEVANCE: An estimated 72 000 cases of unrepaired CL/P are found in India. Poor states with less health care infrastructure have exceptionally high rates (eg, Bihar). These estimates are useful for informing international and national CL/P care strategies, allocating resources, and advocating for individuals and families affected by CL/P more broadly. LEVEL OF EVIDENCE: NA. PMID- 27281158 TI - In Situ Metabolism of Cinnamyl Alcohol in Reconstructed Human Epidermis: New Insights into the Activation of This Fragrance Skin Sensitizer. AB - Chemical modification of epidermal proteins by skin sensitizers is the molecular event which initiates the induction of contact allergy. However, not all chemical skin allergens react directly as haptens with epidermal proteins but need either a chemical (prehaptens) or metabolic (prohaptens) activation step to become reactive. Cinnamyl alcohol has been considered a model prohapten, as this skin sensitizer has no intrinsic reactivity. Therefore, the prevailing theory is that cinnamyl alcohol is enzymatically oxidized into the protein-reactive cinnamaldehyde, which is the sensitizing agent. Knowing that reconstructed human epidermis (RHE) models have been demonstrated to be quite similar to the normal human epidermis in terms of metabolic enzymes, use of RHE may be useful to investigate the in situ metabolism/activation of cinnamyl alcohol, particularly when coupled with high-resolution magic angle spinning nuclear magnetic resonance. Incubation of carbon-13 substituted cinnamyl derivatives with RHE did not result in the formation of cinnamaldehyde. The metabolites formed suggest the formation of an epoxy-alcohol and an allylic sulfate as potential electrophiles. These data suggest that cinnamyl alcohol is inducing skin sensitization through a route independent of the one involving cinnamaldehyde and should therefore be considered as a skin sensitizer on its own. PMID- 27281160 TI - Unacceptable failure of the PI2(r) implant. AB - : The PI2(r) spacer is designed for treatment of trapeziometacarpal (TM) osteoarthritis. However, the shape of this implant has raised concerns about its stability. We retrospectively investigated 45 implants in 41 patients treated for trapeziometacarpal osteoarthritis in our hospital between 2004 and 2009 who underwent trapeziectomy and insertion of a PI2(r) spacer. Outcome parameters included revision rates and clinical outcomes correlated with implant position and scaphometacarpal distance, assessed using standard radiographs. A total of 12 implants (27%) were removed at a median time of 10 months (interquartile range (IQR), 7-22 months). These included five dislocations and one early infection. Additionally, a further six patients underwent revision due to persistent pain. Three of these had scapho-trapezoid osteoarthritis, two had developed subluxation of the implant, and one did not show any radiographic abnormalities. A review of patient records revealed that 33 implants remained in place at a median time of 29 months (IQR, 20-57). However, of those, only 21 implants (64%) in 17 patients were available for clinical evaluation at a median follow-up of 29 months (IQR, 19-62 months). No significant differences in clinical outcomes including functional results were observed between in-place ( n = 8) and subluxated ( n = 13) implants. Due to the high revision rate (12/45), consistent with other reports in the literature, we have abandoned the use of the PI2(r) spacer. We recommend the establishment of a registry for evaluation of future implants. TYPE OF STUDY/LEVEL OF EVIDENCE: Case-series study/level IV. PMID- 27281159 TI - Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure. AB - Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl) diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl) diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma alpha-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases. PMID- 27281161 TI - Characterisation of a novel light activated adhesive scaffold: Potential for device attachment. AB - The most common methods for attaching a device to the internal tissues of the human body are via sutures, clips or staples. These attachment techniques require penetration and manipulation of the tissue. Tears and leaks can often be a complication post-attachment, and scarring usually occurs around the attachment sites. To resolve these issues, it is proposed to develop a soft tissue scaffold impregnated with Rose Bengal/Chitosan solution (RBC-scaffold, 0.01% w/v Rose Bengal, 1.7% w/v Medium Molecular Weight Chitosan). This scaffold will initially attach to the tissue via a light activation method. The light activates the dye in the scaffold which causes cross-links to form between the scaffold and tissue, thus adhering them together. This is done without mechanically manipulating the surrounding tissue, thus avoiding the issues associated with current techniques. Eventually, the scaffold will be resorbed and tissue will integrate for long-term attachment. A variety of tests were performed to characterise the RBC-scaffold. Porosity, interconnectivity, and mechanical strength were measured. Light activation was performed with a broad spectrum (380-780nm) 10W LED lamp exposed to various time lengths (2-15min, Fluence range 0.4-3J/cm(2) ). Adhesive strength of the light-activated bond was measured with lap-shear tests performed on porcine stomach tissue. Cell culture viability was also assessed to confirm tissue integration potential. These properties were compared to VariotisTM, an aliphatic polyester soft tissue scaffold which has proven to be viable for soft tissue regeneration. The RBC-scaffolds were found to have high porosity (86.46+/ 2.95%) and connectivity, showing rapid fluid movement. The elastic modulus of the RBC-scaffolds (3.55+/-1.28MPa) was found to be significantly higher than the controls (0.15+/-0.058MPa, p<0.01) and approached reported values for human gastrointestinal tissue (2.3MPa). The maximum adhesion strength achieved of the RBC-scaffolds was 8.61+/-2.81kPa after 15min of light activation, this is comparable to the adhesion strength of fibrin glue on scaffolds. Cell attachment was seen to be similar to the controls, but cells appeared to have better cell survivability. In conclusion, the RBC-scaffolds show promise for use as a novel light activated attachment device with potential applications in attaching an anti-reflux valve in the lower oesophagus and also in wound healing applications for stomach ulcers. PMID- 27281162 TI - Mini-interfacial fracture toughness as a new validated enamel-bonding effectiveness test. AB - Today's most commonly applied bonding effectiveness tests are criticized for their high variability and low reliability, the latter in particular with regard to measuring the actual strength of the adhesive interface. OBJECTIVES: in continuation of previous research conducted at dentin, we hereby aimed to validate the novel mini-interfacial fracture toughness (mini-iFT) test on its applicability to assess bonding effectiveness of contemporary adhesives when bonded to enamel. METHODS: The 3-step etch&rinse (E&R) adhesive OptiBond FL (Kerr), the 2-step self-etch (SE) adhesive Clearfil SE Bond (Kuraray Noritake) and the two multi-mode adhesives Clearfil S(3) Bond Plus (Kuraray Noritake) and Scotchbond Universal (3M ESPE), both used following a 2-step E&R and 1-step SE mode, were applied to clinically relevant, flattened enamel surfaces. A composite (Filtek Z100; 3M ESPE) build-up was made in layers. After 1-week water storage at 37 degrees C, all specimens were sectioned perpendicular to the interface to obtain rectangular sticks. A mini-iFT notch was prepared at the adhesive-enamel interface using a thin diamond blade under water cooling. Finally, the specimens were loaded in a 4-point bending test until failure. RESULTS: the mini-iFT onto human enamel was significantly higher for the adhesives applied in E&R mode versus those applied in SE mode. The lowest mini-iFT was found for the adhesives applied following a 1-step SE approach. SEM fracture analysis revealed that all fractures originated at the adhesive-enamel interface and that the induced crack propagated preferentially along this interface. CONCLUSION: mini-iFT appeared a valid alternative method to assess the mechanical properties of adhesive-enamel interfaces. PMID- 27281163 TI - Structural and mechanical characterisation of the peri-prosthetic tissue surrounding loosened hip prostheses. An explorative study. AB - Very little is known about the structure and properties of peri-prosthetic fibrous tissue that is found around loose orthopaedic implants. We describe a method for characterizing the structural organisation (histology, confocal microscopy) as well as the nano- and micro-scale mechanical behaviour (atomic force microscopy, nanoindentation) of peri-prosthetic fibrous tissue. The tissue was collected from 11 patients undergoing revision surgery due to aseptic loosening. Sirius Red and Movat histological staining procedures indicated that the tissue mainly consists of collagen fibres and ground substance. However, large inter- and intra-patient variations in the relative proportions of these tissue components were found, as well as in collagen fibre orientation and possibly also maturation. The nano-scale Young's moduli ranged from 0-950kPa, but showed large inter-patient variability. When the results per sample were presented in a probability density function, we could roughly discriminate one peak in the 0-100kPa range and/or one peak in the 100-500Pa range. These nano scale moduli seem to respectively present the mechanical properties of glycosaminoglycan (GAG) and collagen molecules. The majority of the micro-scale Young's moduli ranged between 0.5 and 2.0kPa for all samples. This explorative study provides new insights in (the variations of) structural organisation and mechanical properties of peri-prosthetic tissue. PMID- 27281164 TI - The in vitro passive elastic response of chicken pectoralis muscle to applied tensile and compressive deformation. AB - The mechanics of passive skeletal muscle are important in impact biomechanics, surgical simulation, and rehabilitation engineering. Existing data from porcine tissue has shown a significant tension/compression asymmetry, which is not captured by current constitutive modelling approaches using a single set of material parameters, and an adequate explanation for this effect remains elusive. In this paper, the passive elastic deformation properties of chicken pectoralis muscle are assessed for the first time, to provide deformation data on a skeletal muscle which is very different to porcine tissue. Uniaxial, quasi-static compression and tensile tests were performed on fresh chicken pectoralis muscle in the fibre and cross-fibre directions, and at 45 degrees to the fibre direction. Results show that chicken muscle elastic behaviour is nonlinear and anisotropic. The tensile stress-stretch response is two orders of magnitude larger than in compression for all directions tested, which reflects the tension/compression asymmetry previously observed in porcine tissue. In compression the tissue is stiffest in the cross-fibre direction. However, tensile deformation applied at 45 degrees gives the stiffest response, and this is different to previous findings relating to porcine tissue. Chicken muscle tissue is most compliant in the fibre direction for both tensile and compressive applied deformation. Generally, a small percentage of fluid exudation was observed in the compressive samples. In the future these data will be combined with microstructural analysis to assess the architectural basis for the tension/compression asymmetry now observed in two different species of skeletal muscle. PMID- 27281165 TI - Additive manufacturing and mechanical characterization of graded porosity scaffolds designed based on triply periodic minimal surface architectures. AB - Since the advent of additive manufacturing techniques, triply periodic minimal surfaces have emerged as a novel tool for designing porous scaffolds. Whereas scaffolds are expected to provide multifunctional performance, spatially changing pore patterns have been a promising approach to integrate mechanical characteristics of different architectures into a unique scaffold. Smooth morphological variations are also frequently seen in nature particularly in bone and cartilage structures and can be inspiring for designing of artificial tissues. In this study, we carried out experimental and numerical procedures to uncover the mechanical properties and deformation mechanisms of linearly graded porosity scaffolds for two different mathematically defined pore structures. Among TPMS-based scaffolds, P and D surfaces were subjected to gradient modeling to explore the mechanical responses for stretching and bending dominated deformations, respectively. Moreover, the results were compared to their corresponding uniform porosity structures. Mechanical properties were found to be by far greater for the stretching dominated structure (P-Surface). For bending dominated architecture (D-Surface), although there was no global fracture for uniform structures, graded structure showed a brittle fracture at 0.08 strain. A layer by layer deformation mechanism for stretching dominated structure was observed. For bending dominated scaffolds, deformation was accompanied by development of 45 degrees shearing bands. Finite element simulations were also performed and the results showed a good agreement with the experimental observations. PMID- 27281166 TI - Proteinases as Biomarkers in Breast Cancer Prognosis and Diagnosis. AB - BACKGROUND: Breast cancer is the second leading cause of cancer-related deaths among women in the Western World. METHOD: Upon diagnosis and treatment in the preinvasive state, the five years survival rate levitate up to 93%, making early detection crucial for dedicative diagnosis and treatment. Currently, mammography is the most efficacious diagnostic modality. However, this technique does not match the ultimate sensitivity. Other routinely used biomarkers include tumor size, histological type, nuclear and cellular characteristics, mitotic index, vascular invasion, hormonal and axillary lymph node status were not good enough to predict the course of cancer. To date, researchers revealed a change in the level of some proteinases in breast cancer tissue and reported the role of these proteinases in tumor aggressiveness and patient response to therapy. CONCLUSION: This review summarizes the potential role of serine proteinases (including urokinasedependent plasminogen activator and kallikreins) and zinc metalloproteinases (including matrix metalloproteinase and A disintegrin and metalloproteinase) as either a prognostic and/or diagnostic breast cancer biomarkers. These proteinases plus genetic biomarkers could be implemented in the development of multiplex bio sensing platform toward early breast cancer detection, diagnosis, monitor progression and therapeutic success. PMID- 27281167 TI - Trypanosoma cruzi Invasion into Host Cells: A Complex Molecular Targets Interplay. AB - Chagas' disease is still a worldwide threat, with estimated from 6 to 7 million infected people, mainly in Latin America. Despite all efforts, especially from international consortia (DNDi, NMTrypI), to develop an innovative therapeutic strategy against this disease, no candidate has achieved full requirements for clinical use yet. In this review, we point out the general molecular and cellular mechanisms involved in T. cruzi cell invasion and elucidate the roles of specific parasite and host targets in the progress of Chagas' disease. Among these molecular targets are Gp85/transsialidase, mucins, cruzipain and oligopeptidase B, found in parasite cell surface, and Galectin-3 and Toll-like receptors present in host cells. Thus, the deep understanding of their interplay and involvement on T. cruzi host cell adhesion, invasion and evasion from host immune may expand the chances for discovering new therapeutic agents against this neglected disease. Additionally, these targets may represent a remarkable strategy to block parasite invasion in the early stages of infection. PMID- 27281168 TI - In situ remediation-released zero-valent iron nanoparticles impair soil ecosystems health: A C. elegans biomarker-based risk assessment. AB - There is considerable concern over the potential ecotoxicity to soil ecosystems posed by zero-valent iron nanoparticles (Fe(0) NPs) released from in situ environmental remediation. However, a lack of quantitative risk assessment has hampered the development of appropriate testing methods used in environmental applications. Here we present a novel, empirical approach to assess Fe(0) NPs associated soil ecosystems health risk using the nematode Caenorhabditis elegans as a model organism. A Hill-based dose-response model describing the concentration-fertility inhibition relationships was constructed. A Weibull model was used to estimate thresholds as a guideline to protect C. elegans from infertility when exposed to waterborne or foodborne Fe(0) NPs. Finally, the risk metrics, exceedance risk (ER) and risk quotient (RQ) of Fe(0) NPs in various depths and distances from remediation sites can then be predicted. We showed that under 50% risk probability (ER=0.5), upper soil layer had the highest infertility risk (95% confidence interval: 13.18-57.40%). The margins of safety and acceptable criteria for soil ecosystems health for using Fe(0) NPs in field scale applications were also recommended. Results showed that RQs are larger than 1 in all soil layers when setting a stricter threshold of ~1.02mgL(-1) of Fe(0) NPs. This C. elegans biomarker-based risk model affords new insights into the links between widespread use of Fe(0) NPs and environmental risk assessment and offers potential environmental implications of metal-based NPs for in situ remediation. PMID- 27281170 TI - Erratum: Bacopaside I ameliorates cognitive impairment in APP/PS1 mice via immune mediated clearance of beta-amyloid. PMID- 27281169 TI - Effect of operational strategies on activated sludge's acclimation to phenol, subsequent aerobic granulation, and accumulation of polyhydoxyalkanoates. AB - Aerobic granules, a relative novel form of microbial aggregate, are capable of degrading many toxic organic pollutants. Appropriate strategy is needed to acclimate seed sludge to the toxic compounds for successful granulation. In this study, two distinct strategies, i.e. mixed or single carbon sources, were experimented to obtain phenol-acclimated sludge. Their effects on reactor performance, biomass characteristics, microbial population and the granulation process were analyzed. Sludge fed with phenol alone exhibited faster acclimation and earlier appearance of granules, but possibly lower microbial diversity and reactor stability. Using a mixture of acetate and phenol in the acclimation stage, on the other hand, led to a reactor with slower phenol degradation and granulation, but eventual formation of strong and stable aerobic granules. In addition, the content of intracellular polyhydoxyakanoates (PHA) was also monitored, and significant accumulation was observed during the pre-granulation stage, where PHA >50% of dry weight was observed in both reactors. PMID- 27281171 TI - Role of Twist1 Phosphorylation in Angiogenesis and Pulmonary Fibrosis. AB - Idiopathic pulmonary fibrosis is a chronic and progressive lung disease in which microvessel remodeling is deregulated. However, the mechanism by which deregulated angiogenesis contributes to the pathogenesis of pulmonary fibrosis remains unclear. Here we show that a transcription factor, Twist1, controls angiogenesis through the angiopoietin-Tie2 pathway, and that deregulation of this mechanism mediates pathological angiogenesis and collagen deposition in a bleomycin-induced mouse pulmonary fibrosis model. Twist1 knockdown decreases Tie2 expression and attenuates endothelial cell sprouting in vitro. Angiogenesis is also inhibited in fibrin gel implanted on Tie2-specific Twist1 conditional knockout (Twist1fl/fl/Tie2-cre) mouse lung in vivo. Inhibition of Twist1 phosphorylation at the serine 42 (Ser42) residue by treating endothelial cells with a mutant construct (Twist1S42A) decreases Tie2 expression and attenuates angiogenesis compared with full-length Twist1 in vitro and in vivo. Bleomycin challenge up-regulates Twist1 Ser42 phosphorylation and Tie2 expression, increases blood vessel density, and induces collagen deposition in the mouse lung, whereas these effects are attenuated in Twist1fl/fl/Tie2-cre mice or in mice treated with Twist1S42A mutant construct. These results indicate that Twist1 Ser42 phosphorylation contributes to the pathogenesis of bleomycin-induced pulmonary fibrosis through angiopoietin-Tie2 signaling. PMID- 27281172 TI - Strong Dipolar Effects on an Octupolar Luminiscent Chromophore: Implications on their Linear and Nonlinear Optical Properties. AB - Design parameters derived from structure-property relationships play a very important role in the development of efficient molecular-based functional materials with optical properties. Here, we report on the linear and nonlinear optical properties of a fluorene-derived dipolar system (DS) and its octupolar analogue (OS), in which donor and acceptor groups are connected by a phenylacetylene linkage, as a strategy to increase the number of delocalized electrons in the pi-conjugated system. The optical nonlinear response was analyzed in detail by experimental and theoretical methods, showing that, in the octupolar system OS, the dipolar effects induced a strong two-photon absorption process whose magnitude is as large as 2210 GM at infrared wavelengths. Solvatochromism studies were implemented to obtain further insight on the charge transfer process. We found that the triple bond plays a fundamental role in the linear and nonlinear optical responses. The strong solvatochromism behavior in DS and OS was analyzed by using four empirical solvent scales, namely Lippert Mataga, Kamlet-Taft, Catalan, and the recently proposed scale of Laurence et al., finding consistent results of strong solvent polarizability and viscosity dependence. Finally, the role of the acceptor groups was further studied by synthesizing the analogous compound 2DS, having no acceptor group. PMID- 27281173 TI - Mechanism and Reaction Pathways for Microcystin-LR Degradation through UV/H2O2 Treatment. AB - Microcystin-LR (MCLR) is the most common cyanotoxin in contaminated aquatic systems. MCLR inhibits protein phosphatases 1 and 2A, leading to liver damage and tumor formation. MCLR is relatively stable owing to its cyclic structures. The combined UV/H2O2 technology can degrade MCLR efficiently. The second-order rate constant of the reaction between MCLR and hydroxyl radical (.OH) is 2.79(+/ 0.23)*1010 M-1 s-1 based on the competition kinetics model using nitrobenzene as reference compound. The probable degradation pathway was analyzed through liquid chromatography mass spectrometry. Results suggested that the major destruction pathways of MCLR were initiated by .OH attack on the benzene ring and diene of the Adda side chain. The corresponding aldehyde or ketone peptide residues were formed through further oxidation. Another minor destruction pathway involved .OH attack on the methoxy group of the Adda side chain, followed by complete removal of the methoxy group. The combined UV/H2O2 system is a promising technology for MCLR removal in contaminated aquatic systems. PMID- 27281174 TI - Proteomics of Durum Wheat Grain during Transition to Conservation Agriculture. AB - Nitrogen management in combination with sustainable agronomic techniques can have a great impact on the wheat grain proteome influencing its technological quality. In this study, proteomic analyses were used to document changes in the proportion of prolamins in mature grains of the newly released Italian durum wheat cv Achille. Such an approach was applied to wheat fertilized with urea (UREA) and calcium nitrate (NITRATE), during the transition to no-till Conservation Agriculture (CA) practice in a Mediterranean environment. Results obtained in a two-years field experiment study suggest low molecular weight glutenins (LMW-GS) as the fraction particularly inducible regardless of the N-form. Quantitative analyses of LMW-GS by 2D-GE followed by protein identification by LC-ESI-MS/MS showed that the stable increase was principally due to C-type LMW-GS. The highest accumulation resulted from a physiologically healthier state of plants treated with UREA and NITRATE. Proteomic analysis on the total protein fraction during the active phase of grain filling was also performed. For both N treatments, but at different extent, an up-regulation of different classes of proteins was observed: i) enzymes involved in glycolysis and citric acid cycles which contribute to an enhanced source of energy and carbohydrates, ii) stress proteins like heat shock proteins (HSPs) and antioxidant enzymes, such as peroxidases and superoxide dismutase which protect the grain from abiotic stress during starch and storage protein synthesis. In conclusion N inputs, which combined rate with N form gave high yield and improved quality traits in the selected durum wheat cultivar. The specific up-regulation of some HSPs, antioxidant enzymes and defense proteins in the early stages of grain development and physiological indicators related to fitness traits, could be useful bio-indicators, for wheat genotype screening under more sustainable agronomic conditions, like transition phase to no-till CA in Mediterranean environments. PMID- 27281177 TI - Immune Sensing of Lipopolysaccharide in Plants and Animals: Same but Different. PMID- 27281176 TI - Molecular Hydrogen as a Neuroprotective Agent. AB - Oxidative stress and neuroinflammation cause many neurological disorders. Recently, it has been reported that molecular hydrogen (H2) functions as an antioxidant and anti-inflammatory agent. The routes of H2 administration in animal model and human clinical studies are roughly classified into three types, inhalation of H2 gas, drinking H2-dissolved water, and injection of H2-dissolved saline. This review discusses some of the remarkable progress that has been made in the research of H2 use for neurological disorders, such as cerebrovascular diseases, neurodegenerative disorders, and neonatal brain disorders. Although most neurological disorders are currently incurable, these studies suggest the clinical potential of H2 administration for their prevention, treatment, and mitigation. Several of the potential effectors of H2 will also be discussed, including cell signaling molecules and hormones that are responsible for preventing oxidative stress and inflammation. Nevertheless, further investigation will be required to determine the direct target molecule of H2. PMID- 27281178 TI - Dural carotid cavernous fistulas: endovascular treatment and assessment of the correlation between clinical symptoms and the Cognard classification system. AB - OBJECTIVE: To present our experience with endovascular treatment of dural carotid cavernous fistulas (DCCFs) and determine if there is a correlation between clinical symptoms and the Cognard classification system. METHODS: We searched our institutional neurovascular database to identify patients treated for DCCFs from January 1995 to May 2015. DCCFs were defined as a vascular shunt between meningeal branches of the internal carotid artery (ICA), external carotid artery (ECA), or both, draining into the cavernous sinus. Clinical symptoms were recorded based on clinical examination. Lesions were classified on angiography using the Cognard and Barrow classification systems. Treatment goal was defined as symptomatic cure based on clinical examination, cure of ophthalmic venous drainage, and cortical venous reflux on angiography. RESULTS: The search revealed 37 patients with DCCFs; 32 DCCFs underwent endovascular treatment. The primary treatment goal was met in 30/32 (94%) lesions, with one neurologic complication (1/34; 3%). We identified 31 Cognard IIa fistulas, 4 Cognard IIa+b, 2 Cognard IIb, 7 Barrow B, 7 Barrow C, and 23 Barrow D fistulas. Eye redness, proptosis, and ocular pain were significantly lower in the Cognard IIb group than in the Cognard IIa and IIa+b groups (p=0.0015). Intracranial hemorrhage was more likely in the Cognard IIb group than in the Cognard IIa and IIa+b groups, with marginal significance (p=0.054). No correlation was seen between symptomatology and the Barrow classification. CONCLUSIONS: Endovascular treatment of DCCFs has a high degree of clinical success and a low complication rate. The Cognard system is suitable for grading DCCFs as it correlates with presenting symptomatology and venous drainage patterns. The Barrow classification adds no value in grading DCCFs. PMID- 27281175 TI - Acetylcholinesterase Inhibitors and Drugs Acting on Muscarinic Receptors- Potential Crosstalk of Cholinergic Mechanisms During Pharmacological Treatment. AB - BACKGROUND: Pharmaceuticals with targets in the cholinergic transmission have been used for decades and are still fundamental treatments in many diseases and conditions today. Both the transmission and the effects of the somatomotoric and the parasympathetic nervous systems may be targeted by such treatments. Irrespective of the knowledge that the effects of neuronal signalling in the nervous systems may include a number of different receptor subtypes of both the nicotinic and the muscarinic receptors, this complexity is generally overlooked when assessing the mechanisms of action of pharmaceuticals. METHODS: We have search of bibliographic databases for peer-reviewed research literature focused on the cholinergic system. Also, we have taken advantage of our expertise in this field to deduce the conclusions of this study. RESULTS: Presently, the life cycle of acetylcholine, muscarinic receptors and their effects are reviewed in the major organ systems of the body. Neuronal and non-neuronal sources of acetylcholine are elucidated. Examples of pharmaceuticals, in particular cholinesterase inhibitors, affecting these systems are discussed. The review focuses on salivary glands, the respiratory tract and the lower urinary tract, since the complexity of the interplay of different muscarinic receptor subtypes is of significance for physiological, pharmacological and toxicological effects in these organs. CONCLUSION: Most pharmaceuticals targeting muscarinic receptors are employed at such large doses that no selectivity can be expected. However, some differences in the adverse effect profile of muscarinic antagonists may still be explained by the variation of expression of muscarinic receptor subtypes in different organs. However, a complex pattern of interactions between muscarinic receptor subtypes occurs and needs to be considered when searching for selective pharmaceuticals. In the development of new entities for the treatment of for instance pesticide intoxication, the muscarinic receptor selectivity needs to be considered. Reactivators generally have a muscarinic M2 receptor acting profile. Such a blockade may engrave the situation since it may enlarge the effect of the muscarinic M3 receptor effect. This may explain why respiratory arrest is the major cause for deaths by esterase blocking. PMID- 27281179 TI - A pilot study of neurointerventional research level of evidence and collaboration. AB - INTRODUCTION: No studies have sought to provide a quantitative or qualitative critique of research in the field of neurointerventional surgery. OBJECTIVE: To analyze recent publications from the Journal of Neurointerventional Surgery (JNIS) to test a new method for assessing research and collaboration. METHODS: We reviewed all JNIS Online First publications from 25 February 2015 to 24 February 2016. All publications-human or non-human research, systematic reviews, meta analyses, or literature reviews-were included; editorials and commentaries were excluded. For each publication, study design, number of patients, authors, contributing centers, and study subject were recorded. Level of evidence was defined using a new scale. RESULTS: A total of 206 articles met inclusion criteria. Only 4% were prospective studies. Twenty-eight per cent of scientific research featured patient series of nine or less. The majority of publications were categorized as low-level evidence (91%). Forty-seven per cent involved individuals from a single center, with 87% having collaboration from three or fewer centers. International collaboration was present in 19%. While 256 institutions from 31 countries were represented, 66% were represented in only one publication. CONCLUSIONS: We queried JNIS Online First articles from a 1-year period in a pilot study to test a new method of analyzing research quality and collaboration. The methodology appears to adequately quantify the studies into evidence tiers that emulate previously published, widely accepted scales. This may be useful for future comparison of peer-reviewed journals or for studying the quality of research being performed in different disease processes or medical specialties. PMID- 27281180 TI - Ten Simple Rules for Effective Statistical Practice. PMID- 27281181 TI - Anesthesia Residents Have a Negative Opinion on Proposed ACGME Changes to the Curriculum: A Pilot Study. AB - BACKGROUND: The ACGME has proposed changes to the curriculum for anesthesia residents. These changes include increasing critical care from 2 to 4 months, pain from 1 to 3 months, and obstetrics, pediatric, neuroanesthesia, and cardio thoracic anesthesia from 1 to 2 months. In addition, they have included a preoperative clinic for 1 month. METHODS: With IRB approval, a survey of the anesthesia residents at New York University was distributed. The residents questioned ranged from the CA-1 to the Ca-3 class. The survey questioned the residents on their current curriculum and the proposed changes. RESULTS: 22 Residents completed the questionnaire. Seventy-seven percent of the residents polled felt they had enough experience in critical care with the current requirements and 82% did not want the increase to 4 months (p=0.007). Seventy three percent of the residents responded that their pain management exposure was sufficient and 82% did not want it increased (p=0.011). Overwhelmingly, 82% of those polled felt an entire month of preoperative clinic was not necessary. Seventy-three percent of those residents polled would not be comfortable on subspecialty rotations as early as August of their CA-1 year. 82% felt that too much of their training would be spent outside of the operating room, and the majority (59%) thought more residents would be on each rotation. Moreover, 55% think that the proposed changes will adversely affect residents in training. DISCUSSION: The results of this survey demonstrate that most residents at New York University do not think the current curriculum should change. The majority opinion is that it will negative impact their education. PMID- 27281182 TI - Local Immune Responses in Children and Adults with Allergic and Nonallergic Rhinitis. AB - BACKGROUND: Allergic rhinitis (AR) is the most common allergic disease but little is known about the difference of local immune responses in children and adults with AR. OBJECTIVE: To compare local immune responses between children and adults with AR and nonallergic rhinitis (NAR), and to investigate whether the association of local and systemic immune responses is different between the two age groups. METHODS: Fifty-one patients with chronic rhinitis were enrolled and grouped into children (N = 27, mean age 7.2 years) and adults (N = 24, mean age 29.9 years). Diagnosis of AR was based on symptoms, skin prick tests and serum specific IgEs. Nasal lavage (NAL) fluids were collected from all subjects and used to measure the levels of total IgE, specific IgEs to house dust mites (Dp and Df), and cytokines (TNF-alpha, IL-4, IL-10, IL-17A and IFN-gamma). Flow cytometry was used to measure inflammatory cell types in NAL fluids. RESULTS: AR had significantly increased local levels of total IgE and specific IgEs to Dp and Df compared with NAR in both age groups (P < 0.05). Nasal eosinophils % (P = 0.01) was significantly increased only in children with AR. Local-systemic correlations of total IgE (r = 0.662, P = 0.000) and eosinophil % (r = 0.461, P = 0.015) between the peripheral blood and NAL fluids were found only in children. Moreover, children had correlations between total IgE and eosinophil % in the peripheral blood (r = 0.629, P = 0.001) and in NAL fluids (r = 0.373, P = 0.061). CONCLUSION: Elevated local IgE is a common feature of AR in children and adults. Local measures in NAR showed naive state of immune response which disagree with the hypothesis of local allergic rhinitis. Children showed intense local inflammation and close local-systemic interactions compared to adults supporting pediatric AR as a distinct feature. PMID- 27281184 TI - The struggle with employee engagement: Measures and construct clarification using five samples. AB - Among scholarly researchers, the Utrecht Work Engagement Scale (UWES) is a popular scale for assessing employee or work engagement. However, challenges to the scale's validity have raised major concerns about the measurement and conceptualization of engagement as a construct. Across 4 field samples, we examined 2 measures of engagement, the UWES and the Job Engagement Scale (JES), in both factor structure and patterns of relationships with theoretically hypothesized antecedents and consequences. In a fifth field sample, we examined the construct-level relationships between engagement and related variables, while controlling for sources of measurement error (i.e., item-specific factor, scale specific factor, random response, and transient). By examining 2 measures, each derived from different theoretical bases, we provide unique insight into the measurement and construct of engagement. Our results show that, although correlated, the JES and UWES are not interchangeable. The UWES, more so than the JES, assesses engagement with overlap from other job attitudes, requiring improvement in the measurement of engagement. We offer guidance as to when to use each measure. Furthermore, by isolating the construct versus measurement of engagement relative to burnout, commitment, stress, and psychological meaningfulness and availability, we determined (a) the engagement construct is not the same as the opposite of burnout, warranting a reevaluation of the opposite-of-burnout conceptualization of engagement; and (b) psychological meaningfulness and engagement are highly correlated and likely reciprocally related, necessitating a modification to the self-role-expression conceptualization of engagement. (PsycINFO Database Record PMID- 27281183 TI - Genetic Polymorphisms of Glutathione S-Transferase P1 (GSTP1) and the Incidence of Anti-Tuberculosis Drug-Induced Hepatotoxicity. AB - BACKGROUND: Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is one of the most common adverse effects associated with tuberculosis (TB) therapy. Animal studies have demonstrated important roles of glutathione S-transferases in the prevention of chemical-induced hepatotoxicity. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of glutathione S-transferase P1 (GSTP1) and ATDH in TB patients. METHODS: We used two independent samples for this genetic association study. In the initial prospective study, 322 newly diagnosed TB patients were followed up for three months after initiating anti-TB therapy. In an independent retrospective study, 115 ATDH patients and 116 patients without ATDH were selected to verify the results of the prospective study. Tag-SNPs of GSTP1 were genotyped either with the MassARRAY platform or the improved multiple ligase detection reaction (iMLDR) method. The associations between SNPs and ATDH were analyzed by logistic regression analysis adjusting for confounding factors. RESULTS: Of the 322 patients recruited in the prospective cohort, 35 were excluded during the 3 months of follow-up, and 30 were diagnosed with ATDH and were considered as the ATDH group. The remaining 257 subjects without ATDH were considered as the non ATDH group. After correction for potential confounding factors, significant differences were found for rs1695 (A>G) under an allelic model (OR = 3.876, 95%CI: 1.258011.905; P = 0.018). In the retrospective study, rs1695 allele A also had a higher risk of ATDH (OR = 2.10, 95%CI: 1.17-3.76; P = 0.012). We only found rs4147581AA genotype under a dominant model was related to ATDH in the prospective study (OR = 2.578, 95%CI: 1.076-6.173; P = 0.034). CONCLUSIONS: This is the first study to suggest that GSTP1 genotyping can be an important tool for identifying patients who are susceptible to ATDH. This result should be verified in independent large sample studies and also in other ethnic populations. PMID- 27281185 TI - Actions speak louder than words: Outsiders' perceptions of diversity mixed messages. AB - To attract a gender diverse workforce, many employers use diversity statements to publicly signal that they value gender diversity. However, this often represents a misalignment between words and actions (i.e., a diversity mixed message) because most organizations are male dominated, especially in board positions. We conducted 3 studies to investigate the potentially indirect effect of such diversity mixed messages through perceived behavioral integrity on employer attractiveness. In Study 1, following a 2 * 2 design, participants (N = 225) were either shown a pro gender diversity statement or a neutral statement, in combination with a gender diverse board (4 men and 4 women) or a uniform all-male board (8 men). Participants' perceived behavioral integrity of the organization was assessed. In Study 2, participants (N = 251) either read positive or negative reviews of the organization's behavioral integrity. Employer attractiveness was then assessed. Study 3 (N = 427) investigated the impact of board gender composition on perceived behavioral integrity and employer attractiveness using a bootstrapping procedure. Both the causal-chain design of Study 1 and 2, as well as the significance test of the proposed indirect relationship in Study 3, revealed that a diversity mixed message negatively affected an organization's perceived behavioral integrity, and low behavioral integrity in turn negatively impacted employer attractiveness. In Study 3, there was also evidence for a tipping point (more than 1 woman on the board was needed) with regard to participants' perceptions of the organization's behavioral integrity. (PsycINFO Database Record PMID- 27281186 TI - Expressing pride: Effects on perceived agency, communality, and stereotype-based gender disparities. AB - Two experimental studies were conducted to investigate how the expression of pride shapes agency-related and communality-related judgments, and how those judgments differ when the pride expresser is a man or a woman. Results indicated that the expression of pride (as compared to the expression of happiness) had positive effects on perceptions of agency and inferences about task-oriented leadership competence, and negative effects on perceptions of communality and inferences about people-oriented leadership competence. Pride expression also elevated ascriptions of interpersonal hostility. For agency-related judgments and ascriptions of interpersonal hostility, these effects were consistently stronger when the pride expresser was a woman than a man. Moreover, the expression of pride was found to affect disparities in judgments about men and women, eliminating the stereotype-consistent differences that were evident when happiness was expressed. With a display of pride women were not seen as any more deficient in agency-related attributes and competencies, nor were they seen as any more exceptional in communality-related attributes and competencies, than were men. (PsycINFO Database Record PMID- 27281187 TI - An integrative formal model of motivation and decision making: The MGPM*. AB - We develop and test an integrative formal model of motivation and decision making. The model, referred to as the extended multiple-goal pursuit model (MGPM*), is an integration of the multiple-goal pursuit model (Vancouver, Weinhardt, & Schmidt, 2010) and decision field theory (Busemeyer & Townsend, 1993). Simulations of the model generated predictions regarding the effects of goal type (approach vs. avoidance), risk, and time sensitivity on prioritization. We tested these predictions in an experiment in which participants pursued different combinations of approach and avoidance goals under different levels of risk. The empirical results were consistent with the predictions of the MGPM*. Specifically, participants pursuing 1 approach and 1 avoidance goal shifted priority from the approach to the avoidance goal over time. Among participants pursuing 2 approach goals, those with low time sensitivity prioritized the goal with the larger discrepancy, whereas those with high time sensitivity prioritized the goal with the smaller discrepancy. Participants pursuing 2 avoidance goals generally prioritized the goal with the smaller discrepancy. Finally, all of these effects became weaker as the level of risk increased. We used quantitative model comparison to show that the MGPM* explained the data better than the original multiple-goal pursuit model, and that the major extensions from the original model were justified. The MGPM* represents a step forward in the development of a general theory of decision making during multiple-goal pursuit. (PsycINFO Database Record PMID- 27281188 TI - Safety in the c-suite: How chief executive officers influence organizational safety climate and employee injuries. AB - According to social learning theory, powerful and high status individuals can significantly influence the behaviors of others. In this paper, we propose that chief executive officers (CEOs) indirectly impact frontline injuries through the collective social learning experiences and effort of different groups of organizational actors-including members of the top management team (TMT), organizational supervisors, and frontline employees. We found support for our collective social learning model using data from 2,714 frontline employees, 1,398 supervisors, and 229 members of TMTs in 54 organizations. TMT members' experiences within a CEO-driven TMT safety climate was positively related to organizational supervisors' reports of the broader organizational safety climate and their subsequent collective support for safety (reported by frontline employees). In turn, supervisory support for safety was associated with fewer employee injuries at the individual level. We discuss the theoretical and practical implications of these findings for workplace safety research and practice. (PsycINFO Database Record PMID- 27281189 TI - Assessing the Spatial Variability of Alfalfa Yield Using Satellite Imagery and Ground-Based Data. AB - Understanding the temporal and spatial variability in a crop yield is viewed as one of the key steps in the implementation of precision agriculture practices. Therefore, a study on a center pivot irrigated 23.5 ha field in Saudi Arabia was conducted to assess the variability in alfalfa yield using Landsat-8 imagery and a hay yield monitor data. In addition, the study was designed to also explore the potential of predicting the alfalfa yield using vegetation indices. A calibrated yield monitor mounted on a large rectangular hay baler was used to measure the actual alfalfa yield for four alfalfa harvests performed in the period from October 2013 to May 2014. A total of 18 Landsat-8 images, representing different crop growth stages, were used to derive different vegetation indices (VIs). Data from the yield monitor was used to generate yield maps, which illustrated a definite spatial variation in alfalfa yield across the experimental field for the four studied harvests as indicated by the high spatial correlation values (0.75 to 0.97) and the low P-values (4.7E-103 to 8.9E-27). The yield monitor-measured alfalfa actual yield was compared to the predicted yield form the Vis. Results of the study showed that there was a correlation between actual and predicted yield. The highest correlations were observed between actual yield and the predicted using NIR reflectance, SAVI and NDVI with maximum correlation coefficients of 0.69, 0.68 and 0.63, respectively. PMID- 27281190 TI - RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats. AB - Tubulointerstitial fibrosis (TIF) is caused by the progressive loss of renal tubular cells and the consequent replacement of the extracellular matrix. The progressive depletion of renal tubular cells results from apoptosis and necroptosis; however, the relative significance of each of these cell death mechanisms at different stages during the progression of chronic kidney disease (CKD) remains unclear. We sought to explore the mechanisms of renal tubular cell death during the early and intermediate stages of chronic renal damage of subtotal nephrectomied (SNx) rats. The results of tissue histological assays indicated that the numbers of necrotic dying cells and apoptotic cells were significantly higher in kidney tissues derived from a rat model of CKD. In addition, there was a significant increase in necroptosis observed by transmission electron microscopy (TEM) and an increase in the proportion of TUNEL positive cells in kidney tissues from SNx rats compared with control rats, and necrostatin-1 (Nec-1) could inhibit necroptosis and reduce the proportion of TUNEL-positive cells. More importantly, we observed a significant increase in the incidence of necroptosis compared with apoptosis by TEM in vivo and in vitro and a significant increase in the proportion of TUNEL-positive tubular epithelial cells that did not express caspase-3 compared with those expressing cleaved caspase-3 in vitro. Furthermore, treatment with Nec-1 and zVAD strongly reduced necroptosis- and apoptosis-mediated renal tubular cell death and decreased the levels of blood urea nitrogen and serum creatinine and tubular damage scores of SNx rats. These results suggest that necroptotic cell death plays a more significant role than apoptosis in mediating the loss of renal tubular cells in SNx rats and that effectively blocking both necroptosis and apoptosis improves renal function and tubular damage at early and intermediate stages of CKD. PMID- 27281191 TI - Characteristics and Distribution of Phosphorus in Surface Sediments of Limnetic Ecosystem in Eastern China. AB - Phosphorus (P) is an essential nutrient for aquatic organisms; however, excessive P inflow to limnetic ecosystems can induce eutrophication. P concentrations in the rivers, wetlands and lakes of Eastern China have been amplified by fertilizer and sewage inputs associated with the development of industry and agriculture. Yet, knowledge of the distribution and speciation of P is lacking at the regional scale. We determined the distribution and speciation of P in limnetic ecosystems in Eastern China using Standards, Measurements and Testing (SMT) and phosphorus nuclear magnetic resonance (31P-NMR). The results indicate that P pollution in surface sediments was serious. Inorganic P (Pi) was the primary drive of variation in total P (TP) among different river systems, and Pi accounted for 71% to 90% of TP in surface sediment in Eastern China. Also, the concentrations of TP and Pi varied among watersheds and Pi primarily drove the variation in TP in different watersheds. Sediments less than 10-cm deep served as the main P reservoir. Environmental factors affect the speciation and origin of P. NaOH-Pi, HCl-Pi and organic P (Po) were related to pH accordingly at the regional scale. The physicochemical properties of sediments from different limnetic ecosystems affect the P speciation. HCl-Pi was higher in wetland sediments than in riverine and lake sediments in Eastern China. Conversely, NaOH-Pi was lowest in wetland sediments. Total Po concentration was lower in riverine sediments than in other sediments, but Mono-P was higher, with an average concentration of 48 mg kg-1. Diesters-P was highest in lake sediments. By revealing the regional distribution of TP, Pi and Po, this study will support eutrophication management in Eastern China. PMID- 27281192 TI - Corrigendum: Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases. PMID- 27281193 TI - Structural basis for amino acid export by DMT superfamily transporter YddG. AB - The drug/metabolite transporter (DMT) superfamily is a large group of membrane transporters ubiquitously found in eukaryotes, bacteria and archaea, and includes exporters for a remarkably wide range of substrates, such as toxic compounds and metabolites. YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis. Here we present structural and functional analyses of YddG. Using liposome-based analyses, we show that Escherichia coli and Starkeya novella YddG export various amino acids. The crystal structure of S. novella YddG at 2.4 A resolution reveals a new membrane transporter topology, with ten transmembrane segments in an outward-facing state. The overall structure is basket-shaped, with a large substrate-binding cavity at the centre of the molecule, and is composed of inverted structural repeats related by two-fold pseudo-symmetry. On the basis of this intramolecular symmetry, we propose a structural model for the inward-facing state and a mechanism of the conformational change for substrate transport, which we confirmed by biochemical analyses. These findings provide a structural basis for the mechanism of transport of DMT superfamily proteins. PMID- 27281194 TI - Structural basis of N(6)-adenosine methylation by the METTL3-METTL14 complex. AB - Chemical modifications of RNA have essential roles in a vast range of cellular processes. N(6)-methyladenosine (m(6)A) is an abundant internal modification in messenger RNA and long non-coding RNA that can be dynamically added and removed by RNA methyltransferases (MTases) and demethylases, respectively. An MTase complex comprising methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) efficiently catalyses methyl group transfer. In contrast to the well studied DNA MTase, the exact roles of these two RNA MTases in the complex remain to be elucidated. Here we report the crystal structures of the METTL3-METTL14 heterodimer with MTase domains in the ligand-free, S-adenosyl methionine (AdoMet) bound and S-adenosyl homocysteine (AdoHcy)-bound states, with resolutions of 1.9, 1.71 and 1.61 A, respectively. Both METTL3 and METTL14 adopt a class I MTase fold and they interact with each other via an extensive hydrogen bonding network, generating a positively charged groove. Notably, AdoMet was observed in only the METTL3 pocket and not in METTL14. Combined with biochemical analysis, these results suggest that in the m(6)A MTase complex, METTL3 primarily functions as the catalytic core, while METTL14 serves as an RNA-binding platform, reminiscent of the target recognition domain of DNA N(6)-adenine MTase. This structural information provides an important framework for the functional investigation of m(6)A. PMID- 27281195 TI - Solid-state harmonics beyond the atomic limit. AB - Strong-field laser excitation of solids can produce extremely nonlinear electronic and optical behaviour. As recently demonstrated, this includes the generation of high harmonics extending into the vacuum-ultraviolet and extreme ultraviolet regions of the electromagnetic spectrum. High harmonic generation is shown to occur fundamentally differently in solids and in dilute atomic gases. How the microscopic mechanisms in the solid and the gas differ remains a topic of intense debate. Here we report a direct comparison of high harmonic generation in the solid and gas phases of argon and krypton. Owing to the weak van der Waals interaction, rare (noble)-gas solids are a near-ideal medium in which to study the role of high density and periodicity in the generation process. We find that the high harmonic generation spectra from the rare-gas solids exhibit multiple plateaus extending well beyond the atomic limit of the corresponding gas-phase harmonics measured under similar conditions. The appearance of multiple plateaus indicates strong interband couplings involving multiple single-particle bands. We also compare the dependence of the solid and gas harmonic yield on laser ellipticity and find that they are similar, suggesting the importance of electron hole recollision in these solids. This implies that gas-phase methods such as polarization gating for attosecond pulse generation and orbital tomography could be realized in solids. PMID- 27281196 TI - Fission and reconfiguration of bilobate comets as revealed by 67P/Churyumov Gerasimenko. AB - The solid, central part of a comet--its nucleus--is subject to destructive processes, which cause nuclei to split at a rate of about 0.01 per year per comet. These destructive events are due to a range of possible thermophysical effects; however, the geophysical expressions of these effects are unknown. Separately, over two-thirds of comet nuclei that have been imaged at high resolution show bilobate shapes, including the nucleus of comet 67P/Churyumov Gerasimenko (67P), visited by the Rosetta spacecraft. Analysis of the Rosetta observations suggests that 67P's components were brought together at low speed after their separate formation. Here, we study the structure and dynamics of 67P's nucleus. We find that sublimation torques have caused the nucleus to spin up in the past to form the large cracks observed on its neck. However, the chaotic evolution of its spin state has so far forestalled its splitting, although it should eventually reach a rapid enough spin rate to do so. Once this occurs, the separated components will be unable to escape each other; they will orbit each other for a time, ultimately undergoing a low-speed merger that will result in a new bilobate configuration. The components of four other imaged bilobate nuclei have volume ratios that are consistent with a similar reconfiguration cycle, pointing to such cycles as a fundamental process in the evolution of short-period comet nuclei. It has been shown that comets were not strong contributors to the so-called late heavy bombardment about 4 billion years ago. The reconfiguration process suggested here would preferentially decimate comet nuclei during migration to the inner solar system, perhaps explaining this lack of a substantial cometary flux. PMID- 27281197 TI - Seafloor geodetic constraints on interplate coupling of the Nankai Trough megathrust zone. AB - Interplate megathrust earthquakes have inflicted catastrophic damage on human society. Such an earthquake is predicted to occur in the near future along the Nankai Trough off southwestern Japan--an economically active and densely populated area in which megathrust earthquakes have already occurred. Megathrust earthquakes are the result of a plate-subduction mechanism and occur at slip deficit regions (also known as 'coupling' regions), where friction prevents plates from slipping against each other and the accumulated energy is eventually released forcefully. Many studies have attempted to capture distributions of slip deficit rates (SDRs) in order to predict earthquakes. However, these studies could not obtain a complete view of the earthquake source region, because they had no seafloor geodetic data. The Hydrographic and Oceanographic Department of the Japan Coast Guard (JHOD) has been developing a precise and sustainable seafloor geodetic observation network in this subduction zone to obtain information related to offshore SDRs. Here, we present seafloor geodetic observation data and an offshore interplate SDR-distribution model. Our data suggest that most offshore regions in this subduction zone have positive SDRs. Specifically, our observations indicate previously unknown regions of high SDR that will be important for tsunami disaster mitigation, and regions of low SDR that are consistent with distributions of shallow slow earthquakes and subducting seamounts. This is the first direct evidence that coupling conditions might be related to these seismological and geological phenomena. Our findings provide information for inferring megathrust earthquake scenarios and interpreting research on the Nankai Trough subduction zone. PMID- 27281198 TI - Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain. AB - Voltage-gated sodium (Nav) channels initiate action potentials in most neurons, including primary afferent nerve fibres of the pain pathway. Local anaesthetics block pain through non-specific actions at all Nav channels, but the discovery of selective modulators would facilitate the analysis of individual subtypes of these channels and their contributions to chemical, mechanical, or thermal pain. Here we identify and characterize spider (Heteroscodra maculata) toxins that selectively activate the Nav1.1 subtype, the role of which in nociception and pain has not been elucidated. We use these probes to show that Nav1.1-expressing fibres are modality-specific nociceptors: their activation elicits robust pain behaviours without neurogenic inflammation and produces profound hypersensitivity to mechanical, but not thermal, stimuli. In the gut, high-threshold mechanosensitive fibres also express Nav1.1 and show enhanced toxin sensitivity in a mouse model of irritable bowel syndrome. Together, these findings establish an unexpected role for Nav1.1 channels in regulating the excitability of sensory nerve fibres that mediate mechanical pain. PMID- 27281201 TI - Cell reprogramming: Brain versus brawn. PMID- 27281199 TI - Aberrant PD-L1 expression through 3'-UTR disruption in multiple cancers. AB - Successful treatment of many patients with advanced cancer using antibodies against programmed cell death 1 (PD-1; also known as PDCD1) and its ligand (PD L1; also known as CD274) has highlighted the critical importance of PD-1/PD-L1 mediated immune escape in cancer development. However, the genetic basis for the immune escape has not been fully elucidated, with the exception of elevated PD-L1 expression by gene amplification and utilization of an ectopic promoter by translocation, as reported in Hodgkin and other B-cell lymphomas, as well as stomach adenocarcinoma. Here we show a unique genetic mechanism of immune escape caused by structural variations (SVs) commonly disrupting the 3' region of the PD L1 gene. Widely affecting multiple common human cancer types, including adult T cell leukaemia/lymphoma (27%), diffuse large B-cell lymphoma (8%), and stomach adenocarcinoma (2%), these SVs invariably lead to a marked elevation of aberrant PD-L1 transcripts that are stabilized by truncation of the 3'-untranslated region (UTR). Disruption of the Pd-l1 3'-UTR in mice enables immune evasion of EG7-OVA tumour cells with elevated Pd-l1 expression in vivo, which is effectively inhibited by Pd-1/Pd-l1 blockade, supporting the role of relevant SVs in clonal selection through immune evasion. Our findings not only unmask a novel regulatory mechanism of PD-L1 expression, but also suggest that PD-L1 3'-UTR disruption could serve as a genetic marker to identify cancers that actively evade anti tumour immunity through PD-L1 overexpression. PMID- 27281200 TI - TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. AB - When integral membrane proteins are visualized in detergents or other artificial systems, an important layer of information is lost regarding lipid interactions and their effects on protein structure. This is especially relevant to proteins for which lipids have both structural and regulatory roles. Here we demonstrate the power of combining electron cryo-microscopy with lipid nanodisc technology to ascertain the structure of the rat TRPV1 ion channel in a native bilayer environment. Using this approach, we determined the locations of annular and regulatory lipids and showed that specific phospholipid interactions enhance binding of a spider toxin to TRPV1 through formation of a tripartite complex. Furthermore, phosphatidylinositol lipids occupy the binding site for capsaicin and other vanilloid ligands, suggesting a mechanism whereby chemical or thermal stimuli elicit channel activation by promoting the release of bioactive lipids from a critical allosteric regulatory site. PMID- 27281203 TI - Tunable two-dimensional arrays of single Rydberg atoms for realizing quantum Ising models. AB - Spin models are the prime example of simplified many-body Hamiltonians used to model complex, strongly correlated real-world materials. However, despite the simplified character of such models, their dynamics often cannot be simulated exactly on classical computers when the number of particles exceeds a few tens. For this reason, quantum simulation of spin Hamiltonians using the tools of atomic and molecular physics has become a very active field over the past years, using ultracold atoms or molecules in optical lattices, or trapped ions. All of these approaches have their own strengths and limitations. Here we report an alternative platform for the study of spin systems, using individual atoms trapped in tunable two-dimensional arrays of optical microtraps with arbitrary geometries, where filling fractions range from 60 to 100 per cent. When excited to high-energy Rydberg D states, the atoms undergo strong interactions whose anisotropic character opens the way to simulating exotic matter. We illustrate the versatility of our system by studying the dynamics of a quantum Ising-like spin-1/2 system in a transverse field with up to 30 spins, for a variety of geometries in one and two dimensions, and for a wide range of interaction strengths. For geometries where the anisotropy is expected to have small effects on the dynamics, we find excellent agreement with ab initio simulations of the spin-1/2 system, while for strongly anisotropic situations the multilevel structure of the D states has a measurable influence. Our findings establish arrays of single Rydberg atoms as a versatile platform for the study of quantum magnetism. PMID- 27281202 TI - Translation readthrough mitigation. AB - A fraction of ribosomes engaged in translation will fail to terminate when reaching a stop codon, yielding nascent proteins inappropriately extended on their C termini. Although such extended proteins can interfere with normal cellular processes, known mechanisms of translational surveillance are insufficient to protect cells from potential dominant consequences. Here, through a combination of transgenics and CRISPR-Cas9 gene editing in Caenorhabditis elegans, we demonstrate a consistent ability of cells to block accumulation of C terminal-extended proteins that result from failure to terminate at stop codons. Sequences encoded by the 3' untranslated region (UTR) were sufficient to lower protein levels. Measurements of mRNA levels and translation suggested a co- or post-translational mechanism of action for these sequences in C. elegans. Similar mechanisms evidently operate in human cells, in which we observed a comparable tendency for translated human 3' UTR sequences to reduce mature protein expression in tissue culture assays, including 3' UTR sequences from the hypomorphic 'Constant Spring' haemoglobin stop codon variant. We suggest that 3' UTRs may encode peptide sequences that destabilize the attached protein, providing mitigation of unwelcome and varied translation errors. PMID- 27281204 TI - Genomics: The language of flowers. PMID- 27281206 TI - Immunotherapy: Cancer vaccine triggers antiviral-type defences. PMID- 27281207 TI - The bacterial DnaA-trio replication origin element specifies single-stranded DNA initiator binding. AB - DNA replication is tightly controlled to ensure accurate inheritance of genetic information. In all organisms, initiator proteins possessing AAA+ (ATPases associated with various cellular activities) domains bind replication origins to license new rounds of DNA synthesis. In bacteria the master initiator protein, DnaA, is highly conserved and has two crucial DNA binding activities. DnaA monomers recognize the replication origin (oriC) by binding double-stranded DNA sequences (DnaA-boxes); subsequently, DnaA filaments assemble and promote duplex unwinding by engaging and stretching a single DNA strand. While the specificity for duplex DnaA-boxes by DnaA has been appreciated for over 30 years, the sequence specificity for single-strand DNA binding has remained unknown. Here we identify a new indispensable bacterial replication origin element composed of a repeating trinucleotide motif that we term the DnaA-trio. We show that the function of the DnaA-trio is to stabilize DnaA filaments on a single DNA strand, thus providing essential precision to this binding mechanism. Bioinformatic analysis detects DnaA-trios in replication origins throughout the bacterial kingdom, indicating that this element is part of the core oriC structure. The discovery and characterization of the novel DnaA-trio extends our fundamental understanding of bacterial DNA replication initiation, and because of the conserved structure of AAA+ initiator proteins these findings raise the possibility of specific recognition motifs within replication origins of higher organisms. PMID- 27281205 TI - Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. AB - Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-alpha (IFNalpha) release by plasmacytoid DCs and macrophages. Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNalpha-dependent rejection of progressive tumours. A phase I dose-escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low dose level, IFNalpha and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-I-IFN-mediated innate immune mechanisms for cancer immunotherapy. PMID- 27281210 TI - Corrigendum: Convergence of terrestrial plant production across global climate gradients. PMID- 27281209 TI - Corrigendum: A novel multiple-stage antimalarial agent that inhibits protein synthesis. PMID- 27281208 TI - Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma. AB - Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance. The genomic alterations that commonly occur in pancreatic cancer include activation of KRAS2 and inactivation of p53 and SMAD4 (refs 2-4). So far, however, it has been challenging to target these pathways therapeutically; thus the search for other key mediators of pancreatic cancer growth remains an important endeavour. Here we show that the stem cell determinant Musashi (Msi) is a critical element of pancreatic cancer progression both in genetic models and in patient-derived xenografts. Specifically, we developed Msi reporter mice that allowed image-based tracking of stem cell signals within cancers, revealing that Msi expression rises as pancreatic intraepithelial neoplasia progresses to adenocarcinoma, and that Msi-expressing cells are key drivers of pancreatic cancer: they preferentially harbour the capacity to propagate adenocarcinoma, are enriched in circulating tumour cells, and are markedly drug resistant. This population could be effectively targeted by deletion of either Msi1 or Msi2, which led to a striking defect in the progression of pancreatic intraepithelial neoplasia to adenocarcinoma and an improvement in overall survival. Msi inhibition also blocked the growth of primary patient-derived tumours, suggesting that this signal is required for human disease. To define the translational potential of this work we developed antisense oligonucleotides against Msi; these showed reliable tumour penetration, uptake and target inhibition, and effectively blocked pancreatic cancer growth. Collectively, these studies highlight Msi reporters as a unique tool to identify therapy resistance, and define Msi signalling as a central regulator of pancreatic cancer. PMID- 27281211 TI - Corrigendum: Cerebral cavernous malformations arise from endothelial gain of MEKK3-KLF2/4 signalling. PMID- 27281212 TI - Corrigendum: A receptor heteromer mediates the male perception of female attractants in plants. PMID- 27281213 TI - Self-assembly of microcapsules via colloidal bond hybridization and anisotropy. AB - Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures. Mutually attractive nanoparticles that are deformable owing to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles. Furthermore, anisotropic colloids with attractive patches can self assemble into open lattices and the colloidal equivalents of molecules and micelles. However, model systems that combine mutual attraction, anisotropy and deformability have not yet been realized. Here we synthesize colloidal particles that combine these three characteristics and obtain self-assembled microcapsules. We propose that mutual attraction and deformability induce directional interactions via colloidal bond hybridization. Our particles contain both mutually attractive and repulsive surface groups that are flexible. Analogously to the simplest chemical bond--in which two isotropic orbitals hybridize into the molecular orbital of H2--these flexible groups redistribute on binding. Via colloidal bond hybridization, isotropic spheres self-assemble into planar monolayers, whereas anisotropic snowman-shaped particles self-assemble into hollow monolayer microcapsules. A modest change in the building blocks thus results in much greater complexity of the self-assembled structures. In other words, these relatively simple building blocks self-assemble into markedly more complex structures than do similar particles that are isotropic or non deformable. PMID- 27281214 TI - Synthetic Landau levels for photons. AB - Synthetic photonic materials are an emerging platform for exploring the interface between microscopic quantum dynamics and macroscopic material properties. Photons experiencing a Lorentz force develop handedness, providing opportunities to study quantum Hall physics and topological quantum science. Here we present an experimental realization of a magnetic field for continuum photons. We trap optical photons in a multimode ring resonator to make a two-dimensional gas of massive bosons, and then employ a non-planar geometry to induce an image rotation on each round-trip. This results in photonic Coriolis/Lorentz and centrifugal forces and so realizes the Fock-Darwin Hamiltonian for photons in a magnetic field and harmonic trap. Using spatial- and energy-resolved spectroscopy, we track the resulting photonic eigenstates as radial trapping is reduced, finally observing a photonic Landau level at degeneracy. To circumvent the challenge of trap instability at the centrifugal limit, we constrain the photons to move on a cone. Spectroscopic probes demonstrate flat space (zero curvature) away from the cone tip. At the cone tip, we observe that spatial curvature increases the local density of states, and we measure fractional state number excess consistent with the Wen-Zee theory, providing an experimental test of this theory of electrons in both a magnetic field and curved space. This work opens the door to exploration of the interplay of geometry and topology, and in conjunction with Rydberg electromagnetically induced transparency, enables studies of photonic fractional quantum Hall fluids and direct detection of anyons. PMID- 27281215 TI - Neural correlates of single-vessel haemodynamic responses in vivo. AB - Neural activation increases blood flow locally. This vascular signal is used by functional imaging techniques to infer the location and strength of neural activity. However, the precise spatial scale over which neural and vascular signals are correlated is unknown. Furthermore, the relative role of synaptic and spiking activity in driving haemodynamic signals is controversial. Previous studies recorded local field potentials as a measure of synaptic activity together with spiking activity and low-resolution haemodynamic imaging. Here we used two-photon microscopy to measure sensory-evoked responses of individual blood vessels (dilation, blood velocity) while imaging synaptic and spiking activity in the surrounding tissue using fluorescent glutamate and calcium sensors. In cat primary visual cortex, where neurons are clustered by their preference for stimulus orientation, we discovered new maps for excitatory synaptic activity, which were organized similarly to those for spiking activity but were less selective for stimulus orientation and direction. We generated tuning curves for individual vessel responses for the first time and found that parenchymal vessels in cortical layer 2/3 were orientation selective. Neighbouring penetrating arterioles had different orientation preferences. Pial surface arteries in cats, as well as surface arteries and penetrating arterioles in rat visual cortex (where orientation maps do not exist), responded to visual stimuli but had no orientation selectivity. We integrated synaptic or spiking responses around individual parenchymal vessels in cats and established that the vascular and neural responses had the same orientation preference. However, synaptic and spiking responses were more selective than vascular responses- vessels frequently responded robustly to stimuli that evoked little to no neural activity in the surrounding tissue. Thus, local neural and haemodynamic signals were partly decoupled. Together, these results indicate that intrinsic cortical properties, such as propagation of vascular dilation between neighbouring columns, need to be accounted for when decoding haemodynamic signals. PMID- 27281216 TI - Pore-forming activity and structural autoinhibition of the gasdermin family. AB - Inflammatory caspases cleave the gasdermin D (GSDMD) protein to trigger pyroptosis, a lytic form of cell death that is crucial for immune defences and diseases. GSDMD contains a functionally important gasdermin-N domain that is shared in the gasdermin family. The functional mechanism of action of gasdermin proteins is unknown. Here we show that the gasdermin-N domains of the gasdermin proteins GSDMD, GSDMA3 and GSDMA can bind membrane lipids, phosphoinositides and cardiolipin, and exhibit membrane-disrupting cytotoxicity in mammalian cells and artificially transformed bacteria. Gasdermin-N moved to the plasma membrane during pyroptosis. Purified gasdermin-N efficiently lysed phosphoinositide/cardiolipin-containing liposomes and formed pores on membranes made of artificial or natural phospholipid mixtures. Most gasdermin pores had an inner diameter of 10-14 nm and contained 16 symmetric protomers. The crystal structure of GSDMA3 showed an autoinhibited two-domain architecture that is conserved in the gasdermin family. Structure-guided mutagenesis demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis. These findings reveal the mechanism for pyroptosis and provide insights into the roles of the gasdermin family in necrosis, immunity and diseases. PMID- 27281217 TI - Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease. AB - Mitochondrial DNA (mtDNA) mutations are maternally inherited and are associated with a broad range of debilitating and fatal diseases. Reproductive technologies designed to uncouple the inheritance of mtDNA from nuclear DNA may enable affected women to have a genetically related child with a greatly reduced risk of mtDNA disease. Here we report the first preclinical studies on pronuclear transplantation (PNT). Surprisingly, techniques used in proof-of-concept studies involving abnormally fertilized human zygotes were not well tolerated by normally fertilized zygotes. We have therefore developed an alternative approach based on transplanting pronuclei shortly after completion of meiosis rather than shortly before the first mitotic division. This promotes efficient development to the blastocyst stage with no detectable effect on aneuploidy or gene expression. After optimization, mtDNA carryover was reduced to <2% in the majority (79%) of PNT blastocysts. The importance of reducing carryover to the lowest possible levels is highlighted by a progressive increase in heteroplasmy in a stem cell line derived from a PNT blastocyst with 4% mtDNA carryover. We conclude that PNT has the potential to reduce the risk of mtDNA disease, but it may not guarantee prevention. PMID- 27281219 TI - Corrigendum: Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1. PMID- 27281218 TI - Co-repressor CBFA2T2 regulates pluripotency and germline development. AB - Developmental specification of germ cells lies at the heart of inheritance, as germ cells contain all of the genetic and epigenetic information transmitted between generations. The critical developmental event distinguishing germline from somatic lineages is the differentiation of primordial germ cells (PGCs), precursors of sex-specific gametes that produce an entire organism upon fertilization. Germ cells toggle between uni- and pluripotent states as they exhibit their own 'latent' form of pluripotency. For example, PGCs express a number of transcription factors in common with embryonic stem (ES) cells, including OCT4 (encoded by Pou5f1), SOX2, NANOG and PRDM14 (refs 2, 3, 4). A biochemical mechanism by which these transcription factors converge on chromatin to produce the dramatic rearrangements underlying ES-cell- and PGC-specific transcriptional programs remains poorly understood. Here we identify a novel co repressor protein, CBFA2T2, that regulates pluripotency and germline specification in mice. Cbfa2t2(-/-) mice display severe defects in PGC maturation and epigenetic reprogramming. CBFA2T2 forms a biochemical complex with PRDM14, a germline-specific transcription factor. Mechanistically, CBFA2T2 oligomerizes to form a scaffold upon which PRDM14 and OCT4 are stabilized on chromatin. Thus, in contrast to the traditional 'passenger' role of a co-repressor, CBFA2T2 functions synergistically with transcription factors at the crossroads of the fundamental developmental plasticity between uni- and pluripotency. PMID- 27281220 TI - Dissecting direct reprogramming from fibroblast to neuron using single-cell RNA seq. AB - Direct lineage reprogramming represents a remarkable conversion of cellular and transcriptome states. However, the intermediate stages through which individual cells progress during reprogramming are largely undefined. Here we use single cell RNA sequencing at multiple time points to dissect direct reprogramming from mouse embryonic fibroblasts to induced neuronal cells. By deconstructing heterogeneity at each time point and ordering cells by transcriptome similarity, we find that the molecular reprogramming path is remarkably continuous. Overexpression of the proneural pioneer factor Ascl1 results in a well-defined initialization, causing cells to exit the cell cycle and re-focus gene expression through distinct neural transcription factors. The initial transcriptional response is relatively homogeneous among fibroblasts, suggesting that the early steps are not limiting for productive reprogramming. Instead, the later emergence of a competing myogenic program and variable transgene dynamics over time appear to be the major efficiency limits of direct reprogramming. Moreover, a transcriptional state, distinct from donor and target cell programs, is transiently induced in cells undergoing productive reprogramming. Our data provide a high-resolution approach for understanding transcriptome states during lineage differentiation. PMID- 27281221 TI - Concerted nucleophilic aromatic substitution with (19)F(-) and (18)F(-). AB - Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain (18)F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a 'leaving group' leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong pi-acceptors in the ortho and/or para position(s). Here we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group tolerant (18)F-deoxyfluorination reaction of phenols, which can be used to synthesize (18)F-PET probes. Selective (18)F introduction, without the need for the common, but cumbersome, azeotropic drying of (18)F, can now be accomplished from phenols as starting materials, and provides access to (18)F-labelled compounds not accessible through conventional chemistry. PMID- 27281223 TI - Controlled fragmentation of multimaterial fibres and films via polymer cold drawing. AB - Polymer cold-drawing is a process in which tensile stress reduces the diameter of a drawn fibre (or thickness of a drawn film) and orients the polymeric chains. Cold-drawing has long been used in industrial applications, including the production of flexible fibres with high tensile strength such as polyester and nylon. However, cold-drawing of a composite structure has been less studied. Here we show that in a multimaterial fibre composed of a brittle core embedded in a ductile polymer cladding, cold-drawing results in a surprising phenomenon: controllable and sequential fragmentation of the core to produce uniformly sized rods along metres of fibre, rather than the expected random or chaotic fragmentation. These embedded structures arise from mechanical-geometric instabilities associated with 'neck' propagation. Embedded, structured multimaterial threads with complex transverse geometry are thus fragmented into a periodic train of rods held stationary in the polymer cladding. These rods can then be easily extracted via selective dissolution of the cladding, or can self heal by thermal restoration to re-form the brittle thread. Our method is also applicable to composites with flat rather than cylindrical geometries, in which case cold-drawing leads to the break-up of an embedded or coated brittle film into narrow parallel strips that are aligned normally to the drawing axis. A range of materials was explored to establish the universality of this effect, including silicon, germanium, gold, glasses, silk, polystyrene, biodegradable polymers and ice. We observe, and verify through nonlinear finite-element simulations, a linear relationship between the smallest transverse scale and the longitudinal break-up period. These results may lead to the development of dynamical and thermoreversible camouflaging via a nanoscale Venetian-blind effect, and the fabrication of large-area structured surfaces that facilitate high-sensitivity bio-detection. PMID- 27281222 TI - Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells. AB - Chronic myeloid leukaemia (CML) arises after transformation of a haemopoietic stem cell (HSC) by the protein-tyrosine kinase BCR-ABL. Direct inhibition of BCR ABL kinase has revolutionized disease management, but fails to eradicate leukaemic stem cells (LSCs), which maintain CML. LSCs are independent of BCR-ABL for survival, providing a rationale for identifying and targeting kinase independent pathways. Here we show--using proteomics, transcriptomics and network analyses--that in human LSCs, aberrantly expressed proteins, in both imatinib responder and non-responder patients, are modulated in concert with p53 (also known as TP53) and c-MYC regulation. Perturbation of both p53 and c-MYC, and not BCR-ABL itself, leads to synergistic cell kill, differentiation, and near elimination of transplantable human LSCs in mice, while sparing normal HSCs. This unbiased systems approach targeting connected nodes exemplifies a novel precision medicine strategy providing evidence that LSCs can be eradicated. PMID- 27281225 TI - Solid waste containing persistent organic pollutants in Serbia: From precautionary measures to the final treatment (case study). AB - Sustainable solid waste management needs more dedicated attention in respect of environmental and human health protection. Solid waste containing persistent organic pollutants is of special concern, since persistent organic pollutants are persistent, toxic and of high risk to human health and the environment. The objective of this investigation was to identify critical points in the Serbian system of solid waste and persistent organic pollutants management, to assure the life cycle management of persistent organic pollutants and products containing these chemicals, including prevention and final destruction. Data were collected from the Serbian competent authorities, and led us to identify preventive actions for solid waste management that should reduce or minimise release of persistent organic pollutants into the environment, and to propose actions necessary for persistent organic pollutants solid waste. The adverse impact of persistent organic pollutants is multidimensional. Owing to the lack of treatment or disposal plants for hazardous waste in Serbia, the only option at the moment to manage persistent organic pollutants waste is to keep it in temporary storage and when conditions are created (primarily financial), such waste should be exported for destruction in hazardous waste incinerators. Meanwhile, it needs to be assured that any persistent organic pollutants management activity does not negatively impact recycling flows or disturb progress towards a more circular economy in Serbia. PMID- 27281224 TI - Serum-Based Oxylipins Are Associated with Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients. AB - INTRODUCTION: Individuals with systolic heart failure are at risk of ventricular arrhythmias and all-cause mortality. Little is known regarding the mechanisms underlying these events. We sought to better understand if oxylipins, a diverse class of lipid metabolites derived from the oxidation of polyunsaturated fatty acids, were associated with these outcomes in recipients of primary prevention implantable cardioverter defibrillators (ICDs). METHODS: Among 479 individuals from the PROSE-ICD study, baseline serum were analyzed and quantitatively profiled for 35 known biologically relevant oxylipin metabolites. Associations with ICD shocks for ventricular arrhythmias and all-cause mortality were evaluated using Cox proportional hazards models. RESULTS: Six oxylipins, 17,18 DiHETE (HR = 0.83, 95% CI 0.70 to 0.99 per SD change in oxylipin level), 19,20 DiHDPA (HR = 0.79, 95% CI 0.63 to 0.98), 5,6-DiHETrE (HR = 0.73, 95% CI 0.58 to 0.91), 8,9-DiHETrE (HR = 0.76, 95% CI 0.62 to 0.95), 9,10-DiHOME (HR = 0.81, 95% CI 0.65 to 1.00), and PGF1alpha (HR = 1.33, 95% CI 1.04 to 1.71) were associated with the risk of appropriate ICD shock after multivariate adjustment for clinical factors. Additionally, 4 oxylipin-to-precursor ratios, 15S-HEPE / FA (20:5 omega3), 17,18-DiHETE / FA (20:5-omega3), 19,20-DiHDPA / FA (20:5-omega3), and 5S HEPE / FA (20:5-omega3) were positively associated with the risk of all-cause mortality. CONCLUSION: In a prospective cohort of patients with primary prevention ICDs, we identified several novel oxylipin markers that were associated with appropriate shock and mortality using metabolic profiling techniques. These findings may provide new insight into the potential biologic pathways leading to adverse events in this patient population. PMID- 27281226 TI - A steady state model of agricultural waste pyrolysis: A mini review. AB - Agricultural waste is one of the main renewable energy resources available, especially in an agricultural country such as Serbia. Pyrolysis has already been considered as an attractive alternative for disposal of agricultural waste, since the technique can convert this special biomass resource into granular charcoal, non-condensable gases and pyrolysis oils, which could furnish profitable energy and chemical products owing to their high calorific value. In this regard, the development of thermochemical processes requires a good understanding of pyrolysis mechanisms. Experimental and some literature data on the pyrolysis characteristics of corn cob and several other agricultural residues under inert atmosphere were structured and analysed in order to obtain conversion behaviour patterns of agricultural residues during pyrolysis within the temperature range from 300 degrees C to 1000 degrees C. Based on experimental and literature data analysis, empirical relationships were derived, including relations between the temperature of the process and yields of charcoal, tar and gas (CO2, CO, H2 and CH4). An analytical semi-empirical model was then used as a tool to analyse the general trends of biomass pyrolysis. Although this semi-empirical model needs further refinement before application to all types of biomass, its prediction capability was in good agreement with results obtained by the literature review. The compact representation could be used in other applications, to conveniently extrapolate and interpolate these results to other temperatures and biomass types. PMID- 27281227 TI - DNA Origami Mask for Sub-Ten-Nanometer Lithography. AB - DNA nanotechnology is currently widely explored and especially shows promises for advanced lithography due to its ability to define nanometer scale features. We demonstrate a 9 * 14 nm(2) hole pattern transfer from DNA origami into an SiO2 layer with a sub-10-nm resolution using anhydrous HF vapor in a semiconductor etching machine. We show that the resulting SiO2 pattern inherits its shape from the DNA structure within a process time ranging from 30 to 60 s at an etching rate of 0.2 nm/s. At 600 s of etching, the SiO2 pattern meets corrosion and the overall etching reaction is blocked. These results, in addition to the entire surface coverage by magnesium occurring on the substrate at a density of 1.1 * 10(15) atom/cm(2), define a process window, fabrication rules, and limits for DNA based lithography. PMID- 27281229 TI - ERRATUM. PMID- 27281228 TI - Co-Occurrence of Health Conditions during Childhood: Longitudinal Findings from the UK Millennium Cohort Study (MCS). AB - AIMS: To identify patterns of stability and change in co-occurrence in children between 5-11 years, and to assess if they vary by socio-demographic factors. METHODS: Data from 9548 singleton children from the UK Millennium Cohort Study (MCS) were assessed for co-occurrence of five common adverse conditions: wheeze; longstanding illness; unfavorable weight; injury; and socio-emotional difficulties. We summed adverse conditions (0-5) for each child at ages 5, 7, and 11 and identified co-occurrence (>=2 conditions). Using multinomial regression, we explored associations between co-occurrence trajectories and child's sex and ethnicity, maternal education, and income quintile. RESULTS: 45.6% of children experienced co-occurrence between 5-11 years (7% experienced constant co occurrence). More children moved into co-occurrence than moved out (16.9 vs. 11.9%). Mutually-adjusted relative risk ratios (aRRR) showed a gradient by maternal education: compared to children with no co-occurrence whose mothers had a higher/degree, children whose mothers had no qualifications were more likely to move into (aRRR = 1.32(95%CI:1.02,1.70)), out of (1.74(1.34,2.26)), have fluctuating (1.52(1.09,2.10)) or constant co-occurrence (2.58(1.76,3.80)). The same gradient (high vs. low) was evident for income quintiles. Girls were less likely to experience co-occurrence. CONCLUSIONS: Co-occurrence of adverse conditions is common during childhood, and trajectories are socially patterned. Child-focused care for lower-income children and boys early in life may prevent and reduce co-occurrence in later childhood. PMID- 27281231 TI - Structure of the Photo-catalytically Active Surface of SrTiO3. AB - A major goal of energy research is to use visible light to cleave water directly, without an applied voltage, into hydrogen and oxygen. Although SrTiO3 requires ultraviolet light, after four decades, it is still the "gold standard" for the photo-catalytic splitting of water. It is chemically robust and can carry out both hydrogen and oxygen evolution reactions without an applied bias. While ultrahigh vacuum surface science techniques have provided useful insights, we still know relatively little about the structure of these electrodes in contact with electrolytes under operating conditions. Here, we report the surface structure evolution of a n-SrTiO3 electrode during water splitting, before and after "training" with an applied positive bias. Operando high-energy X-ray reflectivity measurements demonstrate that training the electrode irreversibly reorders the surface. Scanning electrochemical microscopy at open circuit correlates this training with a 3-fold increase of the activity toward the photo induced water splitting. A novel first-principles joint density functional theory simulation, constrained to the X-ray data via a generalized penalty function, identifies an anatase-like structure as the more active, trained surface. PMID- 27281232 TI - Protection of Vine Plants against Esca Disease by Breathable Electrospun Antifungal Nonwovens. AB - The harmful Esca disease in vine plants caused by wood-inhabiting fungi including Phaeomoniella chlamydospora (Pch) is spreading all across the world. This disease leads to poor vine crops and a slow decline or to a sudden dieback of the vine plants. The pruning wounds of vine plants are the main entry point for Pch. While model experiments with aerosol particles recommend electrospun nonwovens as a suitable barrier to block Pch, tests with living spores show clearly that only electrospun fibrous nonwovens do not prevent Pch invasion. However it is found, that with antifungal additives electrospun nonwovens could be applied successfully for blocking of Pch to infect the substrate. Thereby, a highly useful concept for the protection of vine plants against Esca disease is provided which could also serve as a concept for related plant diseases. PMID- 27281233 TI - Vacuum Sealing Drainage Treatment Combined with Antibiotic-Impregnated Bone Cement for Treatment of Soft Tissue Defects and Infection. AB - BACKGROUND This study aimed to evaluate the combined effect of vacuum sealing drainage (VSD) and antibiotic-loaded bone cement on soft tissue defects and infection. MATERIAL AND METHODS This prospective non-blinded study recruited 46 patients with soft tissue defects and infection from January 2010 to May 2014 and randomly divided them into experimental and control groups (n=23). Patients in the experimental group were treated with VSD and antibiotic-loaded bone cement, while the patients in the control group were treated with VSD only. RESULTS In the experimental group, the wound was healed in 23 cases at 4 weeks postoperatively, of which direct suture was performed in 12 cases, and additional free flap transplantation or skin grafting was performed in 6 cases and 5 cases, respectively. No infection reoccurred in 1-year follow-up. In the control group, the wound was healed in 15 cases at 6 weeks postoperatively, of which direct suture was performed in 8 cases, and additional free flap transplantation or skin grafting was performed in 3 cases and 4 cases, respectively. In the other 8 cases the wound was healed at 8 weeks postoperatively. Infection reoccurred in 3 cases during the follow-up. The experimental group had significantly fewer VSD dressing renewals, shorter time needed until the wound was ready for surgery, shorter duration of antibiotic administration, faster wound healing, and shorter hospital stay than the control group (p<0.01). CONCLUSIONS The combination of VSD and antibiotic bone cement might be a better method for treatment of soft tissue defects and infection. PMID- 27281234 TI - Carbon Nanomembranes. AB - Carbon nanomembranes (CNMs) are synthetic 2D carbon sheets with tailored physical or chemical properties. These depend on the structure, molecular composition, and surroundings on either side. Due to their molecular thickness, they can be regarded as "interfaces without bulk" separating regions of different gaseous, liquid, or solid components and controlling the materials exchange between them. Here, a universal scheme for the fabrication of 1 nm-thick, mechanically stable, functional CNMs is presented. CNMs can be further modified, for example perforated by ion bombardment or chemically functionalized by the binding of other molecules onto the surfaces. The underlying physical and chemical mechanisms are described, and examples are presented for the engineering of complex surface architectures, e.g., nanopatterns of proteins, fluorescent dyes, or polymer brushes. A simple transfer procedure allows CNMs to be placed on various support structures, which makes them available for diverse applications: supports for electron and X-ray microscopy, nanolithography, nanosieves, Janus nanomembranes, polymer carpets, complex layered structures, functionalization of graphene, novel nanoelectronic and nanomechanical devices. To close, the potential of CNMs in filtration and sensorics is discussed. Based on tests for the separation of gas molecules, it is argued that ballistic membranes may play a prominent role in future efforts of materials separation. PMID- 27281235 TI - Associations of ChREBP and Global DNA Methylation with Genetic and Environmental Factors in Chinese Healthy Adults. AB - Age, gender, diet, gene and lifestyle have been reported to affect metabolic status and disease susceptibility through epigenetic pathway. But it remains indistinct that which factors account for certain epigenetic modifications. Our aim was to identify the influencing factors on inter-individual DNA methylation variations of carbohydrate response element binding protein (ChREBP) and global genome in peripheral blood leucocytes (PBLs). ChREBP DNA methylation was determined by bisulfite sequencing, and genomic 5mdC contents were quantified by capillary hydrophilic-interaction liquid chromatography/ in-source fragmentation/ tandem mass spectrometry system in about 300 healthy individuals. Eleven single nucleotide polymorphisms (SNPs) spanning ChREBP and DNA methyltransferase 1 (DNMT1) were genotyped by high resolution melting or PCR-restriction fragment length polymorphism. DNMT1 mRNA expression was analyzed by quantitative PCR. We found ChREBP DNA methylation levels were statistically associated with age (Beta (B) = 0.028, p = 0.006) and serum total cholesterol concentrations (TC) (B = 0.815, p = 0.010), independent of sex, concentrations of triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol (LDL-C), fasting blood glucose and systolic blood pressure, diastolic blood pressure, PBLs counts and classifications. The DNMT1 haplotypes were related to ChREBP (odds ratio (OR) = 0.668, p = 0.029) and global (OR = 0.450, p = 0.015) DNA methylation as well as LDL-C, but not DNMT1 expression. However, only the relation to LDL-C was robust to correction for multiple testing (ORFDR = 1.593, pFDR = 0.013). These results indicated that the age and TC were independent influential factors of ChREBP methylation and DNMT1 variants could probably influence LDL-C to further modify ChREBP DNA methylation. Certainly, sequential comprehensive analysis of the interactions between genetic variants and blood lipid levels on ChREBP and global DNA methylation was required. PMID- 27281236 TI - N-Oleoylethanolamine Reduces Inflammatory Cytokines and Adhesion Molecules in TNF alpha-induced Human Umbilical Vein Endothelial Cells by Activating CB2 and PPAR alpha. AB - Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and cannabinoid receptor 2 (CB2) crucially impact the modulation of inflammation. N Oleoylethanolamine (OEA), a natural agonist of PPAR-alpha, can also up-regulate the expression of CB2 in human umbilical vein endothelial cells (HUVECs) and further shows an antiatherosclerotic effect. Our study was designed to determinate whether OEA could inhibit inflammation in HUVECs induced by tumor necrosis factor-alpha (TNF-alpha) and to identify the mechanism of OEA function. Interleukin-6 (IL-6), interleukin-8 (IL-8), vascular adhesion molecule-1 (VCAM 1), and intercellular adhesion molecule-1 (ICAM-1) levels were detected in HUVECs exposed to tumor necrosis factor-alpha in the presence of OEA. The results showed that OEA suppressed the expression of interleukin-6, interleukin-8, vascular adhesion molecule-1, and intercellular adhesion molecule-1 in a dose-dependent manner. OEA also enhanced CB2 and PPAR-alpha receptor expression, which contributed to its anti-inflammatory effect. OEA inhibited the nuclear factor kappaB (NF-kappaB) pathway, and the effect of OEA on nuclear factor-kappaB was partly abolished when HUVECs were pretreated with either CB2 or PPAR-alpha antagonist. OEA attenuated tumor necrosis factor-alpha-induced inflammation in HUVECs by up-regulating the expression of CB2 and PPAR-alpha receptors. Furthermore, OEA suppresses the nuclear factor-kappaB pathway. These results suggest that OEA exerts anti-inflammatory and anti-adhesive effects on HUVECs. PMID- 27281237 TI - Energetics of surface confined ferritin during iron loading. AB - We report on the first quantitative picture on how iron loading inside ferritin molecules occurs when they are self-assembled onto solid surfaces. Recombinant human ferritin H-chain with ferroxidase activity was adsorbed onto microcantilever beams to form a stable close-packed thin film. The obtained nanomechanical system was used to track in real time the energetics of inter ferritin surface interactions during incubation with Fe(II) for iron loading. We observed that iron loading is accompanied by increasing attractive in-plane inter ferritin interactions able to perform a maximum surface work of 6.0+/-1.5mJ/m(2), corresponding to a surface energy variation per ferritin of about 40kbT. Unique to this protein surface transformation, part of the surface work is exerted by the attractive electrostatic forces arising among the new born nanosized iron cores inside the ferritin shells. The remaining work comes from subtle action of steric, bridging and depletion forces. These findings are of fundamental interest and add important information for the rational development of ferritin nanotechnology. PMID- 27281238 TI - Effective co-delivery of doxorubicin and curcumin using a glycyrrhetinic acid modified chitosan-cystamine-poly(epsilon-caprolactone) copolymer micelle for combination cancer chemotherapy. AB - A glycyrrhetinic acid-modified chitosan-cystamine-poly(epsilon-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(epsilon-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox responsive drug release and GA/pH-mediated endocytosis in vitro. In simulated body fluid with 10mM glutathione, the release rate in 12h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy. PMID- 27281239 TI - Neodymium doped hydroxyapatite theranostic nanoplatforms for colon specific drug delivery applications. AB - Theranostic nanoplatforms integrate therapeutic payloads with diagnostic agents, and help monitor therapeutic response. In this regard, stimuli responsive nanoplatforms further favour combinatorial therapeutic approach that can considerably improve efficacy and specificity of treatment. Herein, we present the engineering of a smart theranostic nanoplatform based on neodymium doped hydroxyapatite (HAN). The presence of neodymium endows the HAN nanoplatforms with near-infrared fluorescence capability. These HAN nanoparticles were then subsequently modified with alginic acid (HANA) to confer pH responsiveness to the synthesized nanoplatforms delivering them to the colon after oral administration. These nanoplatforms possessing optimum size, needle shaped morphology and negative zeta potential, are conducive to cellular internalization. On excitation at 410nm they exhibit near infrared emission at 670nm unraveling their theranostic capabilities. Cytotoxic effects systematically assessed using MTT and live dead assays reveal excellent viability. Raman microscopic imaging technique used to visualize uptake in HeLa cells demonstrate increased uptake from 4 to 16h, with growing cluster size and localization in the cytoplasm. Moreover the concomitant presence of alginic acid manifested advantages of augmented loading and pH dependent release profiles of the model drug, 4 acetyl salicylic acid (4ASA). We could thus establish a theranostic system for early tumour detection, targeted tumour therapy and monitoring of colon cancer that can be administered via the oral route. PMID- 27281240 TI - Foliar penetration enhanced by biosurfactant rhamnolipid. AB - With recent environmental and health concerns, biosurfactants have obtained increasing interest in replacing conventional surfactants for diverse applications. In agriculture, the use of surfactant in stimulating foliar uptake is mainly for wetting leaf surface, resisting deposition/evaporation, enhancing penetration across cuticular membrane (CM) and translocation. This paper aimed to address the improved foliar uptake by rhamnolipid (RL) in comparison with the currently used alkyl polyglucoside (APG). As found, compared with APG at 900mg/L (1*critical micellar concentration, CMC), RL at a much lower concentration of 50mg/L (1*CMC) showed much better wettability and surface activity, indicative of its high effectiveness as surfactants. Its performance on resistance to deposition and evaporation was at least as same as APG. Moreover, RL could significantly improve the penetration of herbicide glyphosate and other two small water-soluble molecules (phenol red and Fe(2+)) across CM at an equivalent efficiency as APG at 1*CMC. Finally, the greatly enhanced herbicidal actitivity of glyphosate on greenhouse plants confirmed that RL and APG could both enhance the foliar uptake including translocation. Overall, RL should be more applicable than APG in agriculture due to its more promising properties on health/environmental friendliness. PMID- 27281241 TI - Organophilic treatments of bentonite increase the adsorption of aflatoxin B1 and protect stem cells against cellular damage. AB - Bentonite clays exhibit high adsorptive capacity for contaminants, including aflatoxin B1 (AFB1), a mycotoxin responsible for causing severe toxicity in several species including pigs, poultry and man. Organophilic treatments is known to increase the adsorption capacity of bentonites, and the primary aim of this study was to evaluate the ability of Brazilian bentonite and two organic salts - benzalkonium chloride (BAC) and cetyltrimethylammonium bromide (CTAB) to adsorb AFB1. For this end, 2(2) factorial designs were used in order to analyze if BAC or CTAB was able to increase AFB1 adsorption when submitted in different temperature and concentration. Both BAC and CTAB treatment (at 30 degrees C and 2% of salt concentration) were found to increase the adsorption of AFB1 significantly compared with untreated bentonite. After organophilic bentonite treatments with BAC or CTAB, a vibration of CH stretch (2850 and 2920cm(-1)) were detected. A frequency of the SiO stretch (1020 and 1090cm(-1)) was changed by intercalation of organic cation. Furthermore, the interlayer spacing of bentonite increases to 1.23nm (d001 reflection at 2theta=7.16) and 1.22 (d001 reflection at 2theta=7.22) after the addition of BAC and CTAB, respectively. Another aim of the study was to observe the effects of these two bentonite salts in neural crest stem cell cultures. The two materials that were created by organophilic treatments were not found to be toxic to stem cells. Furthermore the results indicate that the two materials tested may protect the neural crest stem cells against damage caused by AFB1. PMID- 27281242 TI - Injectable composites via functionalization of 1D nanoclays and biodegradable coupling with a polysaccharide hydrogel. AB - The use of injectable materials in minimally invasive surgical procedures could help in facing the bone diseases connected to the ageing of world population. To this aim, materials integrating the rheological properties of biocompatible polymers with the mechanical properties of 1D inorganic nanostructures represent promising scaffolds. Here we describe the preparation of hydrogel composites made of carboxymethyl cellulose (CMC) and halloysite nanotubes (HNT) as injectable materials for the local treatment of bone defects. The rheology and injectability of the materials reflects their structural properties, showing the possibility of successfully injecting the prepared composites over a large range of operative conditions. PMID- 27281243 TI - Interaction of jack bean (Canavalia ensiformis) urease and a derived peptide with lipid vesicles. AB - Ureases are metalloenzymes that catalyze the hydrolysis of urea to ammonia and carbon dioxide. Jack bean (Canavalia ensiformis) produces three isoforms of urease (Canatoxin, JBU and JBURE-II). Canatoxin and JBU display several biological properties independent of their ureolytic activity, such as neurotoxicity, exocytosis-inducing and pro-inflammatory effects, blood platelets activation, insecticidal and antifungal activities. The Canatoxin entomotoxic activity is mostly due to an internal peptide, named pepcanatox, released upon the hydrolysis of the protein by insect cathepsin-like digestive enzymes. Based on pepcanatox sequence, Jaburetox-2Ec was produced in Escherichia coli. JBU and its peptides were shown to permeabilize membranes through an ion channel-based mechanism. Here we studied the JBU and Jaburetox-2Ec interaction with platelet like multilamellar liposomes (PML) using Dynamic Light Scattering and Small Angle X-ray Scattering techniques. We also analyzed the interaction of JBU with giant unilamellar vesicles (GUVs) using Fluorescence Microscopy. The interaction of vesicles with JBU led to a slight reduction of hydrodynamic radius, and caused an increase in the lamellar repeat distance of PML, suggesting a membrane disordering effect. In contrast, Jaburetox-2Ec decreased the lamellar repeat distance of PML membranes, while also diminishing their hydrodynamic radius. Fluorescence microscopy showed that the interaction of GUVs with JBU caused membrane perturbation with formation of tethers. In conclusion, JBU can interact with PML, probably by inserting its Jaburetox "domain" into the PML external membrane. Additionally, the interaction of Jaburetox-2Ec affects the vesicle's internal bilayers and hence causes more drastic changes in the PML membrane organization in comparison with JBU. PMID- 27281244 TI - Elimination of Mother-to-Child Transmission of HIV - Thailand. AB - Thailand experienced a generalized human immunodeficiency virus (HIV) epidemic during the 1990s. HIV prevalence among pregnant women was 2.0% and the mother-to child transmission (MTCT) rate was >20% (1-3). In June 2016, Thailand became the first country in Asia to validate the elimination of MTCT by meeting World Health Organization (WHO) targets. Because Thailand's experience implementing a successful prevention of MTCT program might be instructive for other countries, Thailand's prevention of MTCT interventions, outcomes, factors that contributed to success, and challenges that remain were reviewed. Thailand's national prevention of MTCT program has evolved with prevention science from national implementation of short course zidovudine (AZT) in 2000 to lifelong highly active antiretroviral therapy regardless of CD4 count (WHO option B+) in 2014 (1). By 2015, HIV prevalence among pregnant women had decreased to 0.6% and the MTCT rate to 1.9% (the elimination of MTCT target is <2% for nonbreastfeeding populations) (4). A strong public health infrastructure, committed political leadership, government funding, engagement of multiple partners, and a robust monitoring system allowed Thailand to achieve this important public health milestone. PMID- 27281245 TI - Total pancreatectomy and islet cell autotransplantation: Definitive treatment for chronic pancreatitis. AB - In appropriately selected patients, total pancreatectomy and islet cell autotransplant controls pain and improves quality of life while often minimizing the development of overt diabetes. Multidisciplinary management and lifelong follow-up help to maximize the benefit of this procedure. This review highlights its history, indications, metabolic outcomes, and future directions. PMID- 27281246 TI - The fifth vital sign: A complex story of politics and patient care. PMID- 27281247 TI - To the Editor: Wilson disease. PMID- 27281248 TI - In Reply: Wilson disease. PMID- 27281249 TI - To the Editor: Cognitive bias and diagnostic error. PMID- 27281250 TI - In Reply: Cognitive bias and diagnostic error. PMID- 27281251 TI - Anticoagulation in dental surgery: Is it rude to interrupt? PMID- 27281252 TI - Multiple linear subcutaneous nodules. PMID- 27281253 TI - Whiplash-shaped acute rash. PMID- 27281254 TI - Should I suspect obstructive sleep apnea if a patient has hard-to-control hypertension? PMID- 27281255 TI - When does chest CT require contrast enhancement? PMID- 27281256 TI - Navigating pneumococcal vaccination in adults. AB - With two nonequivalent vaccines available and different recommendations for different patient populations, vaccination against Streptococcus pneumoniae can be confusing. Here we try to clarify the situation. PMID- 27281257 TI - Opioids for persistent pain in older adults. AB - Older adults compose a large portion of patients with persistent pain. Opioid analgesics are widely used to treat acute and persistent pain in cancer and end of-life care, but their use in other types of persistent pain in older adults is controversial. Clinicians and regulators must work together, balancing the legitimate medical need for opioids while acknowledging increasing opioid misuse and morbidity and mortality related to opioids. PMID- 27281258 TI - A guide to managing acute liver failure. AB - Nearly 2,000 cases of acute liver failure occur each year in the United States. This disease carries a high mortality rate, and early recognition and transfer to a tertiary medical care center with transplant facilities is critical. This article reviews the definition, epidemiology, etiology, and management of acute liver failure. PMID- 27281259 TI - Dietary and medical management of recurrent nephrolithiasis. AB - Dietary approaches and medical treatment can prevent recurrence of urinary stones. Some interventions are appropriate for all types of stones, but there are particular risk factors that may need directed therapy. PMID- 27281260 TI - Transcutaneous electrical acupoint stimulation as an adjunct therapy for obsessive-compulsive disorder: A randomized controlled study. AB - BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS) is thought to have potential to treat obsessive-compulsive disorder (OCD). OBJECTIVE: The purpose of this study was to determine whether adding TEAS to cognitive behavioral therapy (CBT) and clomipramine would improve the efficacy of these conventional treatments in OCD. METHODS: In this randomized controlled trial, 360 OCD patients were assigned to receive TEAS combined with CBT plus clomipramine (Group A, n = 120), TEAS combined with CBT plus placebo (Group B, n = 120), and simulated (placebo) TEAS combined with CBT plus clomipramine (Group C, n = 120) for 12 weeks. The primary outcome was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: OCD symptoms in all patients reduced over time, however Groups A and B had a significantly greater reduction in Y-BOCS total score and the subscale for obsession and compulsion between week 2 and week 12 compared to Group C. Groups A and B had similar scores on these measures. Both groups had significantly higher rates of clinical response than Group C (88.3% and 81.7% vs. 67.5%, respectively, p < 0.001); and higher rates of remission (30.0% and 22.5% vs. 9.2%, respectively, p < 0.001). Group B experienced fewer adverse events than the other two groups. CONCLUSIONS: TEAS enhances the efficacy of conventional OCD interventions and avoids the adverse effects associated with conventional pharmacological treatment. It can be considered as an effective adjunct intervention for OCD. PMID- 27281261 TI - Bipolar disorder course, impaired glucose metabolism and antioxidant enzymes activities: A preliminary report. AB - This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course. PMID- 27281262 TI - Malignant Peripheral Nerve Sheath Tumors: A Single Institution's Experience Using Combined Surgery and Radiation Therapy. AB - PURPOSE: The purpose of this study is to investigate local control (LC), survival outcomes, and associated prognostic factors for patients with malignant peripheral nerve sheath tumors (MPNSTs) treated with combined surgery and radiation therapy (RT). METHODS: We reviewed the medical records of 71 consecutive patients treated with surgery and RT for localized MPNST between 1965 and 2012. Preoperative RT was used to treat 23 patients (32%) to a median dose of 50 Gy (range, 50 to 60 Gy), whereas 48 (68%) received postoperative RT to a median dose of 64 Gy (range, 45 to 70 Gy). RESULTS: Median follow-up for living patients was 118 months (range, 21 to 512 mo). The 5-year LC, distant metastatic free survival, and disease-specific survival rates were 84%, 62%, and 66%, respectively. To identify predictors of outcome, several multivariate models were constructed: (1) positive/uncertain surgical margin status was the only factor adversely associated local relapse at 5 years (28% vs. 5% for negative margins; P=0.02; hazard ratios 5.92; 95% confidence interval, 1.3-27.4). (2) No factors were significantly associated with distant metastatic free survival. Of the 35 patients (49%) who sustained disease relapse, only 3 were ultimately salvaged. Only 2 patients had grade 2 late toxicities (necrosis, fibrosis) based on Common Terminology Criteria for Adverse Events version 4.03 criteria, and 1 patient had grade 1 edema. CONCLUSIONS: Combination therapy with surgery and RT provides favorable LC. Distant recurrences, however, continue to be challenging with limited salvage success at the time of relapse. PMID- 27281263 TI - Targeted Prostate Biopsy Gleason Score Heterogeneity and Implications for Risk Stratification. AB - OBJECTIVES: To quantify Gleason score (GS) heterogeneity within multiparametric magnetic resonance imaging (MRI)-targeted prostate biopsies and to determine impact on National Comprehensive Cancer Network (NCCN) risk stratification. METHODS: An Institutional Review Board-approved retrospective study was performed on men who underwent Artemis (MRI-transrectal-ultrasound fusion) targeted biopsy (TB) for suspected prostate cancer between 2012 and 2015. Intratarget heterogeneity was defined as a difference in GS between 2 cores within a single target in patients with >=2 positive cores. Prostate specific antigen, maximum tumor diameter, apparent diffusion coefficient, MRI suspicion score, prostate volume, systematic biopsy (SB) GS, and T-stage were analyzed for correlation with heterogeneity. Changes in NCCN risk based on high versus low GS on TB, SB alone, and SB+TB were compared. RESULTS: Fifty-three patients underwent TB of 73 suspected lesions. Seventy percent (51/73) had >=2 positive cores, thus meeting inclusion criteria for heterogeneity analysis. Fifty-five percent (28/51) of qualifying targets showed GS heterogeneity. None of the evaluated factors showed a significant relationship with heterogeneity. NCCN low-risk, intermediate-risk, and high-risk groups were 30%, 49%, and 21%, respectively, with SB alone. Adding low GS TB to SB resulted in 17%, 55%, 28% in each risk group, while using high GS+SB resulted in 4%, 54%, and 42%. Overall, the addition of TB resulted in higher NCCN risk groups in 38% of cases. CONCLUSIONS: Over half of multiparametric MRI-defined targets demonstrated GS heterogeneity. The addition of high GS from TB leads to risk inflation compared with using SB alone. Further research is needed on how to integrate these findings into current risk stratification models and clinical practice. PMID- 27281264 TI - Perioperative Mortality in Nonelderly Adult Patients With Cancer: A Population based Study Evaluating Health Care Disparities in the United States According to Insurance Status. AB - OBJECTIVES: The purpose of this study was to evaluate whether insurance status predicts for perioperative mortality (death within 30 d of cancer-directed surgery) for the 20 most common surgically treated cancers. METHODS: The SEER database was examined for the 20 most common surgically resected cancers and included nonelderly adults, aged 18 to 64 years. The database was queried from 2007 to 2011, with a total of 506,722 patients included in the analysis. RESULTS: Insurance status for all patients were the following: non-Medicaid insurance (83%), any Medicaid (10%), uninsured (4%), and unknown (3%). In univariate analyses, predictors for perioperative mortality included insurance status (P<0.001), age (P=0.015), race (P<0.001), marital status (P<0.001), residence (P=0.002), percent of county below the federal poverty level (P<0.001), and median county-level income (P<0.001). Perioperative mortality was also associated with advanced disease (P<0.001). Under multivariate analysis, patients with either Medicaid (Cochran-Mantel-Haenszel odds ratio [CMH OR], 1.21; 95% confidence interval [CI], 1.14-1.29; P<0.001) or uninsured status (CMH OR, 1.56; 95% CI, 1.44-1.70; P<0.001) were more likely to die within 30 days of surgery compared with patients with non-Medicaid insurance. When comparing Medicaid with the uninsured, Medicaid patients had significantly lower rates of perioperative mortality when compared with the uninsured (CMH OR, 0.80; 95% CI, 0.73-0.89, P<0.001). CONCLUSIONS AND RELEVANCE: In the largest reported analysis of perioperative mortality evaluating the 20 most common surgically treated malignancies, patients with Medicaid coverage or without health insurance were more likely to die within 30 days of surgery, with the uninsured having the worst outcomes. PMID- 27281265 TI - The Role of Lymphadenectomy Versus Sentinel Lymph Node Biopsy in Early-stage Endometrial Cancer: A Review of the Literature. AB - OBJECTIVE: The objective of this study is to review existing data regarding the feasibility, diagnostic performance, and oncologic outcomes of sentinel lymph node biopsy (SLNB) versus lymphadenectomy (LND) in endometrial cancer. MATERIALS AND METHODS: A PubMed search identified studies on different staging strategies in endometrial cancer, including routine LND, predictive models of selective nodal dissection, and SLNB. RESULTS: There is ongoing controversy over the risk benefit ratio of LND in assessing nodal involvement in presumed early-stage endometrial cancer. Current experience with sentinel node biopsy suggests high detection rates and low false-negative rates across most series, as well as the increased detection of occult metastatic disease overlooked by conventional pathology. Although data on the long-term oncologic outcomes of sentinel node biopsy in this setting are limited, short-term follow-up shows no immediate impairment of disease-free survival or overall survival rates when compared with LND. CONCLUSIONS: SLNB holds promise as a less-morbid and more accurate alternative to LND for determining nodal spread in early-stage endometrial cancer. Further studies are necessary to understand how lymph node status will guide postoperative management and impact survival of women with nodal metastases. PMID- 27281266 TI - Retrospective Analysis of Cisplatin Nephrotoxicity in Patients With Head and Neck Cancer Receiving Outpatient Treatment With Concurrent High-dose Cisplatin and Radiotherapy. AB - OBJECTIVES: Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck (SCCHN), with nephrotoxicity considered the dose-limiting toxicity. The purpose of our study was to propose an outpatient high-dose cisplatin protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with SCCHN treated with concurrent radiotherapy. MATERIALS AND METHODS: We retrospectively evaluated 82 SCCHN patients treated with outpatient high-dose cisplatin concurrent with radiotherapy at our institution. Acute kidney injury (AKI) and chronic kidney disease were defined by Kidney Disease Improving Global Outcomes criteria. Associated factors were identified using analysis of covariance models for categorical variables and adjusted Pearson correlations for continuous variables. RESULTS: The incidence of AKI during treatment was 34.2%. With a median follow-up of 25.7 months, the average decrease in estimated glomerular filtration rate was 12.57 mL/min/1.73 m (SD=18.58). At 1 year and at last follow-up, 5.4% and 4.4% of patients had estimated glomerular filtration rate <60 mL/min/1.73 m. Predictors associated with AKI and chronic kidney disease were: lower baseline weight and creatinine, higher baseline creatinine clearance, smoking, female sex, African American race, hypertension, and increased hydration and magnesium replacement requirements. CONCLUSIONS: We encountered limited early and late nephrotoxicity. Importantly, nephrotoxicity was not the main dose-limiting toxicity. Our results emphasize the importance of close monitoring and additional replacement of water and electrolytes as needed. A consistent method of measuring and reporting chemotherapy-induced nephrotoxicity would be a valuable contribution to the literature. PMID- 27281267 TI - Effects of Crowding and Environment on the Evolution of Conformational Ensembles of the Multi-Stimuli-Responsive Intrinsically Disordered Protein, Rec1-Resilin: A Small-Angle Scattering Investigation. AB - In this study, we explore the overall structural ensembles and transitions of a biomimetic, multi-stimuli-responsive, intrinsically disordered protein (IDP), Rec1-resilin. The structural transition of Rec1-resilin with change in molecular crowding and environment is evaluated using small-angle neutron scattering and small-angle X-ray scattering. The quantitative analyses of the experimental scattering data using a combination of computational models allowed comprehensive description of the structural evolution, organization, and conformational ensembles of Rec1-resilin in response to the changes in concentration, pH, and temperature. Rec1-resilin in uncrowded solutions demonstrates the equilibrium intrinsic structure quality of an IDP with radius of gyration Rg ~ 5 nm, and a scattering function for the triaxial ellipsoidal model best fit the experimental dataset. On crowding (increase in concentration >10 wt %), Rec1-resilin molecules exert intermolecular repulsive force of interaction, the Rg value reduces with a progressive increase in concentration, and molecular chains transform from a Gaussian coil to a fully swollen coil. It is also revealed that the structural organization of Rec1-resilin dynamically transforms from a rod (pH 2) to coil (pH 4.8) and to globular (pH 12) as a function of pH. The findings further support the temperature-triggered dual-phase-transition behavior of Rec1-resilin, exhibiting rod-shaped structural organization below the upper critical solution temperature (~4 degrees C) and a large but compact structure above the lower critical solution temperature (~75 degrees C). This work attempted to correlate unusual responsiveness of Rec1-resilin to the evolution of conformational ensembles. PMID- 27281268 TI - Illness Cognitions and Coping Self-Efficacy in Depression Among Persons With Low Vision. AB - PURPOSE: To investigate the mediating role of coping self-efficacy (CSE) between two types of illness cognitions (i.e., acceptance and helplessness) and depressive symptoms in persons with low vision. METHODS: This was a single-group, cross-sectional study. Patients with visual acuity < 6/12 in the better eye and at least minimal depressive symptoms (>=5 on the Patient Health Questionnaire-9 [PHQ-9]) were recruited from vision rehabilitation services and participated in telephone-administered structured interviews at one time point. Measures were the PHQ-9, CSE Scale, and Illness Cognition Questionnaire. Structural equation modeling (SEM) devised the causal flow of illness cognitions and their observed indirect effects on depressive symptoms via the CSE mediators: problem focused, emotion focused, and social support. RESULTS: The study comprised 163 patients (mean age 62 years; 61% female), most with age-related macular degeneration (26%) and moderate vision impairment (44%, <6/18-6/60). Structural equation modeling indices indicated a perfect fit (chi2 < 0.001, P = 1.00), accounting for 55% of the variance in depressive symptoms. Lower levels of acceptance and higher levels of helplessness illness cognitions were associated with lower self-efficacy in problem-focused coping (beta = 0.38, P < 0.001, beta = -0.28, P < 0.01, respectively), which in turn was associated with greater depressive symptom severity (beta = -0.54, P < 0.001). CONCLUSIONS: Lack of acceptance and greater helplessness relating to low vision led to a lack of perceived capability to engage in problem-focused coping, which in turn promoted depressive symptoms. Third-wave cognitive-behavioral treatments that focus on acceptance may be efficacious in this population. PMID- 27281269 TI - Connexin 50 Regulates Surface Ball-and-Socket Structures and Fiber Cell Organization. AB - PURPOSE: The roles of gap junction protein connexin 50 (Cx50) encoded by Gja8, during lens development are not fully understood. Connexin 50 knockout (KO) lenses have decreased proliferation of epithelial cells and altered fiber cell denucleation. We further investigated the mechanism for cellular defects in Cx50 KO (Gja8-/-) lenses. METHODS: Fiber cell morphology and subcellular distribution of various lens membrane/cytoskeleton proteins from wild-type and Cx50 KO mice were visualized by immunofluorescent staining and confocal microscopy. RESULTS: We observed multiple morphological defects in the cortical fibers of Cx50 KO lenses, including abnormal fiber cell packing geometry, decreased F-actin enrichment at tricellular vertices, and disrupted ball-and-socket (BS) structures on the long sides of hexagonal fibers. Moreover, only small gap junction plaques consisting of Cx46 (alpha3 connexin) were detected in cortical fibers and the distributions of the BS-associated beta-dystroglycan and ZO-1 proteins were altered. CONCLUSIONS: Connexin 50 gap junctions are important for BS structure maturation and cortical fiber cell organization. Connexin 50-based gap junction plaques likely form structural domains with an array of membrane/cytoskeletal proteins to stabilize BS. Loss of Cx50-mediated coupling, BS disruption, and altered F-actin in Cx50 KO fibers, thereby contribute to the small lens and mild cataract phenotypes. PMID- 27281271 TI - Gas Chromatography/Atmospheric Pressure Chemical Ionization Tandem Mass Spectrometry for Fingerprinting the Macondo Oil Spill. AB - We report the first application of a new mass spectrometry technique (gas chromatography combined to atmospheric pressure chemical ionization tandem mass spectrometry, GC/APCI-MS/MS) for fingerprinting a crude oil and environmental samples from the largest accidental marine oil spill in history (the Macondo oil spill, the Gulf of Mexico, 2010). The fingerprinting of the oil spill is based on a trace analysis of petroleum biomarkers (steranes, diasteranes, and pentacyclic triterpanes) naturally occurring in crude oil. GC/APCI enables soft ionization of petroleum compounds that form abundant molecular ions without (or little) fragmentation. The ability to operate the instrument simultaneously in several tandem mass spectrometry (MS/MS) modes (e.g., full scan, product ion scan, reaction monitoring) significantly improves structural information content and sensitivity of analysis. For fingerprinting the oil spill, we constructed diagrams and conducted correlation studies that measure the similarity between environmental samples and enable us to differentiate the Macondo oil spill from other sources. PMID- 27281272 TI - Assessing autobiographical memory: the web-based autobiographical Implicit Association Test. AB - By assessing the association strength with TRUE and FALSE, the autobiographical Implicit Association Test (aIAT) [Sartori, G., Agosta, S., Zogmaister, C., Ferrara, S. D., & Castiello, U. (2008). How to accurately detect autobiographical events. Psychological Science, 19, 772-780. doi: 10.1111/j.1467-9280.2008.02156.x ] aims to determine which of two contrasting statements is true. To efficiently run well-powered aIAT experiments, we propose a web-based aIAT (web-aIAT). Experiment 1 (n = 522) is a web-based replication study of the first published aIAT study [Sartori, G., Agosta, S., Zogmaister, C., Ferrara, S. D., & Castiello, U. (2008). How to accurately detect autobiographical events. Psychological Science, 19, 772-780. doi: 10.1111/j.1467-9280.2008.02156.x ; Experiment 1]. We conclude that the replication was successful as the web-based aIAT could accurately detect which of two playing cards participants chose (AUC = .88; Hit rate = 81%). In Experiment 2 (n = 424), we investigated whether the use of affirmative versus negative sentences may partly explain the variability in aIAT accuracy findings. The aIAT could detect the chosen card when using affirmative (AUC = .90; Hit rate = 81%), but not when using negative sentences (AUC = .60; Hit rate = 53%). The web-based aIAT seems to be a valuable tool to facilitate aIAT research and may help to further identify moderators of the test's accuracy. PMID- 27281270 TI - Vulnerability of Dopaminergic Amacrine Cells to Chronic Ischemia in a Mouse Model of Oxygen-Induced Retinopathy. AB - PURPOSE: Retinal dopamine deficiency is a potential cause of myopia and visual deficits in retinopathy of prematurity (ROP). We investigated the cellular mechanisms responsible for lowered levels of retinal dopamine in an oxygen induced retinopathy (OIR) mouse model of ROP. METHODS: Retinopathy was induced by exposing mice to 75% oxygen from postnatal day 7 (P7) to P12. Oxygen-induced retinopathy and age-matched control mice were euthanized at P12, P17, P25, or P42 to P50. Immunohistochemistry, electrophysiology, and biochemical approaches were used to determine the effect of OIR on the structure and function of dopaminergic amacrine cells (DACs). RESULTS: The total number of DACs was unchanged in OIR retinas at P12 despite significant capillary dropout in the central retina. However, a significant loss of DACs was observed in P17 OIR retinas (in which neovascularization was maximal), with the cell loss being more profound in the central (avascular) than in the peripheral (neovascular) regions. Cell loss was persistent in both regions at P25, at which time retinal neovascularization had regressed. At P42, the percentage of DACs lost (54%) was comparable to the percent decrease in total dopamine content (53%). Additionally, it was found that DACs recorded in OIR retinas at P42 to P50 had a complete dendritic field and exhibited relatively normal spontaneous and light-induced electrical activity. CONCLUSIONS: The results suggest that remaining DACs are structurally and functionally intact and that loss of DACs is primarily responsible for the decreased levels of retinal dopamine observed after OIR. PMID- 27281273 TI - Air pollution and diabetes association: Modification by type 2 diabetes genetic risk score. AB - Exposure to ambient air pollution (AP) exposure has been linked to type 2 diabetes (T2D) risk. Evidence on the impact of T2D genetic variants on AP susceptibility is lacking. Compared to single variants, joint genetic variants contribute substantially to disease risk. We investigated the modification of AP and diabetes association by a genetic risk score (GRS) covering 63 T2D genes in 1524 first follow-up participants of the Swiss cohort study on air pollution and lung and heart diseases in adults. Genome-wide data and covariates were available from a nested asthma case-control study design. AP was estimated as 10-year mean residential particulate matter <10MUm (PM10). We computed count-GRS and weighted GRS, and applied PM10 interaction terms in mixed logistic regressions, on odds of diabetes. Analyses were stratified by pathways of diabetes pathology and by asthma status. Diabetes prevalence was 4.6% and mean exposure to PM10 was 22MUg/m(3). Odds of diabetes increased by 8% (95% confidence interval: 2, 14%) per T2D risk allele and by 35% (-8, 97%) per 10MUg/m(3) exposure to PM10. We observed a positive interaction between PM10 and count-GRS on diabetes [ORinteraction=1.10 (1.01, 1.20)], associations being strongest among participants at the highest quartile of count-GRS [OR: 1.97 (1.00, 3.87)]. Stronger interactions were observed with variants of the GRS involved in insulin resistance [(ORinteraction=1.22 (1.00, 1.50)] than with variants related to beta cell function. Interactions with count-GRS were stronger among asthma cases. We observed similar results with weighted-GRS. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A and KCNQ1 showed nominally significant interactions with PM10 (P<0.05). Our results suggest that genetic risk for T2D may modify susceptibility to air pollution through alterations in insulin sensitivity. These results need confirmation in diabetes cohort consortia. PMID- 27281274 TI - Apolipoprotein E isotype-dependent modulation of microRNA-146a in plasma and brain. AB - The Apolipoprotein E (ApoE) isotype ApoE4 is a prevalent genetic risk factor for Alzheimer's disease (AD) that can modulate systemic and central inflammation, independent of amyloid accumulation. Although disruption of innate immune toll receptor signaling is modulated by ApoE and observed in AD, ApoE isotype-specific effects remain poorly understood. Therefore, we examined the effect of the ApoE isotype on the brain levels of major regulators of TLR signaling including miR146a, a microRNA enriched in the brain. We used 6-month-old ApoE3 or ApoE4 targeted replacement mice with and without mutant familial AD transgenes. ApoE4 reduced the levels of miR146a compared with ApoE3, both in the brain (29%; P<0.0001) and in plasma (47%; P<0.05), which correlated with each other (r=0.74; P<0.05). The presence of 5xFAD transgenes increased brain miR146a in both ApoE3 (E3FAD) and ApoE4 (E4FAD) mice; however, miR146a levels in E4FAD mice remained lower than those in E3FAD mice (62%; P<0.05), despite increased amyloid and inflammation. Supporting these observations, ApoE4 brains showed increased expression of interleukin receptor-associated kinase-1 (160%; P<0.05) (normally downregulated by miR146) that correlated inversely with miR146a levels (r=0.637; P<0.0001). Reduced negative feedback of toll-like receptor signaling (by miRNA146a) can explain early-life hypersensitivity to innate immune stimuli (including Abeta) in ApoE4 carriers. Thus, ApoE4 causes early dysregulation of a central controller of the innate immune system both centrally and systemically. This defect persists with familial AD pathology and may be relevant to ApoE4 AD risk. PMID- 27281275 TI - Ibuprofen Differentially Affects Supraspinatus Muscle and Tendon Adaptations to Exercise in a Rat Model. AB - BACKGROUND: Previous studies have shown that ibuprofen is detrimental to tissue healing after acute injury; however, the effects of ibuprofen when combined with noninjurious exercise are debated. HYPOTHESIS: Administration of ibuprofen to rats undergoing a noninjurious treadmill exercise protocol will abolish the beneficial adaptations found with exercise but will have no effect on sedentary muscle and tendon properties. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 167 male Sprague-Dawley rats were divided into exercise or cage activity (sedentary) groups and acute (a single bout of exercise followed by 24 hours of rest) and chronic (2 or 8 weeks of repeated exercise) response times. Half of the rats were administered ibuprofen to investigate the effects of this drug over time when combined with different activity levels (exercise and sedentary). Supraspinatus tendons were used for mechanical testing and histologic assessment (organization, cell shape, cellularity), and supraspinatus muscles were used for morphologic (fiber cross-sectional area, centrally nucleated fibers) and fiber type analysis. RESULTS: Chronic intake of ibuprofen did not impair supraspinatus tendon organization or mechanical adaptations (stiffness, modulus, maximum load, maximum stress, dynamic modulus, or viscoelastic properties) to exercise. Tendon mechanical properties were not diminished and in some instances increased with ibuprofen. In contrast, total supraspinatus muscle fiber cross-sectional area decreased with ibuprofen at chronic response times, and some fiber type-specific changes were detected. CONCLUSION: Chronic administration of ibuprofen does not impair supraspinatus tendon mechanical properties in a rat model of exercise but does decrease supraspinatus muscle fiber cross-sectional area. This fundamental study adds to the growing literature on the effects of ibuprofen on musculoskeletal tissues and provides a solid foundation on which future work can build. CLINICAL RELEVANCE: The study findings suggest that ibuprofen does not detrimentally affect regulation of supraspinatus tendon adaptations to exercise but does decrease muscle growth. Individuals should be advised on the risk of decreased muscle hypertrophy when consuming ibuprofen. PMID- 27281276 TI - Reliability and Validity of the Sport Concussion Assessment Tool-3 (SCAT3) in High School and Collegiate Athletes. AB - BACKGROUND: The Sport Concussion Assessment Tool-3 (SCAT3) facilitates sideline clinical assessments of concussed athletes. Yet, there is little published research on clinically relevant metrics for the SCAT3 as a whole. PURPOSE: We documented the psychometric properties of the major SCAT3 components (symptoms, cognition, balance) and derived clinical decision criteria (ie, reliable change score cutoffs and normative conversation tables) for clinicians to apply to cases with and without available preinjury baseline data. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: High school and collegiate athletes (N = 2018) completed preseason baseline evaluations including the SCAT3. Re evaluations of 166 injured athletes and 164 noninjured controls were performed within 24 hours of injury and at 8, 15, and 45 days after injury. Analyses focused on predictors of baseline performance, test-retest reliability, and sensitivity and specificity of the SCAT3 using either single postinjury cutoffs or reliable change index (RCI) criteria derived from this sample. RESULTS: Athlete sex, level of competition, attention-deficit/hyperactivity disorder (ADHD), learning disability (LD), and estimated verbal intellectual ability (but not concussion history) were associated with baseline scores on >=1 SCAT3 components (small to moderate effect sizes). Female sex, high school level of competition (vs college), and ADHD were associated with higher baseline symptom ratings (d = 0.25-0.32). Male sex, ADHD, and LD were associated with lower baseline Standardized Assessment of Concussion (SAC) scores (d = 0.28-0.68). Male sex, high school level of competition, ADHD, and LD were associated with poorer baseline Balance Error Scoring System (BESS) performance (d = 0.14-0.26). After injury, the symptom checklist manifested the largest effect size at the 24-hour assessment (d = 1.52), with group differences diminished but statistically significant at day 8 (d = 0.39) and nonsignificant at day 15. Effect sizes for the SAC and BESS were small to moderate at 24 hours (SAC: d = -0.36; modified BESS: d = 0.46; full BESS: d = 0.51) and became nonsignificant at day 8 (SAC) and day 15 (BESS). Receiver operating characteristic curve analyses demonstrated a stronger discrimination for symptoms (area under the curve [AUC] = 0.86) than cognitive and balance measures (AUCs = 0.58 and 0.62, respectively), with comparable discrimination of each SCAT3 component using postinjury scores alone versus baseline-adjusted scores (P = .71-.90). Normative conversion tables and RCI criteria were created to facilitate the use of the SCAT3 both with and without baseline test results. CONCLUSION: Individual predictors should be taken into account when interpreting the SCAT3. The normative conversion tables and RCIs presented can be used to help interpret concussed athletes' performance both with and without baseline data, given the comparability of the 2 interpretative approaches. PMID- 27281277 TI - The Medial Stitch in Transosseous-Equivalent Rotator Cuff Repair: Vertical or Horizontal Mattress? AB - BACKGROUND: Despite advances in surgical technique, rotator cuff repair retears continue to occur at rates of 10%, 22%, and 57% for small, medium, and large tears, respectively. A common mode of failure in transosseous-equivalent rotator cuff repairs is tissue pullout of the medial mattress stitch. While the medial mattress stitch has been studied extensively, no studies have evaluated a vertical mattress pattern placed near the musculotendinous junction in comparison with a horizontal mattress pattern. HYPOTHESIS: Vertical mattress stitches will have higher load to failure and lower gapping compared with horizontal mattress stitches in a transosseous-equivalent rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: Double-row transosseous-equivalent rotator cuff repairs were performed in 9 pairs of human male cadaveric shoulders (mean age +/- SD, 58 +/- 10 years). One shoulder in each pair received a medial-row suture pattern using a vertical mattress stitch, and the contralateral shoulder received a horizontal mattress. Specimens were mounted in a materials testing machine and tested in uniaxial tensile deformation for cyclic loading (500 cycles at 1 Hz to 1.0 MPa of effective stress), followed by failure testing carried out at a rate of 1 mm/s. Construct gapping and applied loads were monitored continuously throughout the testing. RESULTS: Vertical mattress sutures were placed in 5 right and 4 left shoulders. Peak cyclic gapping did not differ between vertical (mean +/- SD, 2.8 +/- 1.1 mm) and horizontal mattress specimens (3.0 +/- 1.2 mm) (P = .684). Vertical mattress sutures failed at higher loads compared with horizontal mattress sutures (568.9 +/- 140.3 vs 451.1 +/- 174.3 N; P = .025); however, there was no significant difference in failure displacement (8.0 +/- 1.6 vs 6.0 +/- 2.1 mm; P = .092). Failure stiffness did not differ between the suture patterns (P = .204). CONCLUSION: In transosseous-equivalent rotator cuff repairs near the musculotendinous junction, a vertical mattress suture used as the medial stitch has a higher load to failure but no difference in gapping compared with a horizontal mattress pattern. CLINICAL RELEVANCE: A vertical mattress suture may offer enhanced strength of repair for transosseous equivalent repairs. PMID- 27281278 TI - Quantifying Head Impacts in Collegiate Lacrosse. AB - BACKGROUND: Concussion and repetitive head impact in sports has increased interest and concern for clinicians, scientists, and athletes. Lacrosse is the fastest growing sport in the United States, but the burden of head impact in lacrosse is unknown. PURPOSE: The goal of this pilot study was to quantify head impact associated with practicing and playing collegiate lacrosse while subjects were fitted with wearable accelerometers. STUDY DESIGN: Descriptive epidemiology study. METHODS: In a single year, a collegiate cohort of 14 women's and 15 men's lacrosse players wore mastoid-patch accelerometers to measure the frequency and severity of head impacts during official practices and games. Average impact severity, mean number of impacts, and cumulative acceleration were evaluated, stratified by sport and event type. RESULTS: Men's and women's collegiate lacrosse players did not significantly differ in the number of head impacts received during games (11.5 for men vs 9.2 for women) or practices (3.1 vs 3.1). Men's lacrosse players had significantly higher average head acceleration per impact during games compared with women (21.1g vs 14.7g) but not during practices (21.3g vs 18.1g). For both men and women, more impacts occurred during games than during practices (men, 11.5 vs 3.1; women, 9.2 vs 3.1), but impact severity did not significantly differ between events for either sport (men, 21.1g vs 21.3g; women, 14.7g vs 18.1g). CONCLUSION: The study data suggest a higher impact burden during games compared with practices, but this effect is driven by the quantity rather than severity of impacts. In contrast, sex-based effects in impact burden are driven by average impact severity rather than quantity. Data collected from larger multisite trials and/or different age groups could be used to inform ongoing debates, including headgear and practice regulations, that might appreciably affect the burden of head impacts in lacrosse. CLINICAL RELEVANCE: While most head impacts do not result in a clinical diagnosis of concussion, evidence indicates that subconcussive head impacts may increase susceptibility to concussion and contribute to long-term neurodegeneration. PMID- 27281279 TI - Humeral Torsion as a Risk Factor for Shoulder and Elbow Injury in Professional Baseball Pitchers. AB - BACKGROUND: Numerous studies have demonstrated that humeral retrotorsion is increased in the dominant arms of throwing athletes. No study has clearly defined the relationship between humeral retrotorsion and shoulder and elbow injury. HYPOTHESIS: Uninjured professional pitchers will display more dominant humeral torsion (HT) than professional pitchers who sustain shoulder injuries but less than pitchers who sustain elbow injuries. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Pitchers from the Colorado Rockies professional baseball organization were recruited for participation for this prospective injury study from 2009 to 2013. HT was assessed using indirect ultrasonographic techniques and was measured prospectively in 255 pitchers before each spring training (average of 2 trials). From the beginning of the preseason to the end of the postseason, overuse upper extremity injuries (shoulder or elbow) were tracked for each participating athlete. All athletes who reported pain or injury to their coach were referred to the organization's athletic trainer for evaluation and classification of each injury. The difference in HT was calculated by subtracting measurement of the dominant arm from the nondominant arm, and 3 separate mixed model analyses of variance (side * injury group) were used to compare the dominant and nondominant HT between all pitchers who developed an arm injury (shoulder and elbow combined), as well as comparing pitchers who developed a shoulder or elbow injury to those who did not miss games due to shoulder or elbow injury (alpha = .05). RESULTS: During the course of the study, 60 arm (30 shoulder; 30 elbow) injuries were observed; 195 pitchers did not suffer an injury. There were no differences when HT was compared between all injured (shoulder and elbow injuries combined) and uninjured pitchers (P = .13; effect size 0.14). There was a significant interaction effect showing that pitchers who suffered a shoulder injury displayed 4 degrees less dominant humeral retrotorsion compared with pitchers without injury (P = .04) and that pitchers with elbow injury displayed 5 degrees greater humeral retrotorsion (P = .04). In addition, those who suffered an ulnar collateral ligament injury requiring reconstruction (n = 17) also displayed 4(o) greater dominant retrotorsion and 5 degrees less nondominant humeral retrotorsion compared with pitchers who did not suffer an injury (n = 195; P = .05). There was not a significant difference between nondominant HT among pitchers who sustained shoulder and elbow injuries and pitchers without injury. CONCLUSION: The results of this study show a contrast in dominant humeral retrotorsion between pitchers who suffered shoulder and elbow injuries compared with those without an injury. Pitchers who sustained shoulder injuries had less dominant humeral retrotorsion compared with noninjured pitchers. In contrast, pitchers who sustained time-loss elbow injuries displayed increased humeral retrotorsion compared with noninjured pitchers. Together, these results suggest that increased adaptive humeral retrotorsion is protective against shoulder injuries but a harmful contributor for elbow injuries in professional pitchers. This is the first study to show differing injury risk profiles for shoulder and elbow injury. PMID- 27281281 TI - Laboratory Monitoring of Low-Molecular-Weight Heparin and Fondaparinux. AB - Compared with older agents, low-molecular-weight heparins (LMWH) and fondaparinux offer improved bioavailability and more predictable, dose-independent clearance. While routine monitoring of coagulation parameters is not usually necessary with these agents, certain populations (including pregnant patients, children, obese patients, and patients with renal impairment) may benefit from the monitoring of anti-factor Xa activity, thromboelastography, or other coagulation assays to help guide therapy. The chromogenic anti-factor Xa assay is currently the gold standard for monitoring LMWH and fondaparinux therapy. Thromboelastography has been used to monitor LMWH therapy in special situations but is not needed for routine use. PMID- 27281280 TI - Retina regeneration in zebrafish. AB - Unlike mammals, zebrafish are able to regenerate a damaged retina. Key to this regenerative response are Muller glia that respond to retinal injury by undergoing a reprogramming event that allows them to divide and generate a retinal progenitor that is multipotent and responsible for regenerating all major retinal neuron types. The fish and mammalian retina are composed of similar cell types with conserved function. Because of this it is anticipated that studies of retina regeneration in fish may suggest strategies for stimulating Muller glia reprogramming and retina regeneration in mammals. In this review we describe recent advances and future directions in retina regeneration research using zebrafish as a model system. PMID- 27281282 TI - Current Trends in Neonatal Tracheostomy. AB - IMPORTANCE: The indications for neonatal tracheostomy may have changed with current noninvasive respiratory therapies compared with previous decades. OBJECTIVES: To study the current trends in neonatal tracheostomy and identify the primary indication for the procedure and risk factors for failed extubation. DESIGN, SETTING, AND PARTICIPANTS: This retrospective medical record review included 47 neonates who underwent tracheostomy from January 1, 2009, to December 31, 2013, at the University of Maryland Children's Hospital. Group 1 included infants undergoing tracheostomy for the primary indication of upper airway obstruction; group 2, infants with primary pulmonary disease. Data on weight, gestational age, comorbid conditions, congenital abnormalities, complications, outcomes, and indications for tracheostomy were compared statistically between groups. MAIN OUTCOMES AND MEASURES: Differences in gestational age, birth weight, and age at tracheostomy. RESULTS: Among the 47 infants included in the study (30 boys; 17 girls, mean [SD] age, 113 [73] days), 31 (66%) demonstrated anatomical causes of airway obstruction, and 16 (34%) had significant pulmonary disease. Among infants with anatomical causes, subglottic stenosis represented the largest group (11 of 31 [35%]). The mean age at the time of tracheostomy was significantly lower in the group with airway obstruction (98.9 vs 146.9 days; difference, 48 [95% CI, 4.8-91.2] days; P = .04). No procedure-related morbidity or mortality was encountered. CONCLUSIONS AND RELEVANCE: Anatomical upper airway obstruction may be returning as the most common indication for a neonatal tracheostomy, thereby supporting the belief that current respiratory therapies have lowered the burden of chronic lung disease and the need for prolonged ventilatory care. PMID- 27281283 TI - Direct Nucleophilic Difluoromethylation of Carbonyl Compounds. AB - Phosphonium salt ([Ph3P(+)CF2H] Br(-), DFPB) was found to be an efficient nucleophilic difluoromethylation reagent. Although DFPB is known as a phosphonium ylide precursor, its reaction with carbonyl compounds under traditional "Wittig reaction conditions" did not give the expected Wittig difluoroolefinated products, but afforded the nucleophilic difluoromethylation products, alpha-CF2H alcohols. Mechanistic investigation reveals that the unexpected transformation proceeded via the direct transfer of the CF2H group, which resulted from the high P-O affinity. PMID- 27281284 TI - Trapped modes in an infinite or semi-infinite tube with a local enlargement. AB - Trapped modes in a hard cylindrical tube with a local axisymmetric enlargement or bulge and filled with a uniform acoustic medium is studied. The governing Helmholtz equation in the cylindrical coordinate system is employed to deal with this problem through the domain decomposition method and matching technique. The trapped modes and the corresponding frequencies less than the threshold frequency or cut-off frequency are derived. It is found that in addition to the fundamental mode, the second- and higher-order trapped modes exist and depend on the geometry parameters of the local bulge. The effects of the bulge radius and width on the frequencies are discussed. The local bulge leads to a decrease of the frequencies and the corresponding vibration mode is localized near the bulge. A multimodal analysis is made and frequency band gap of generalized trapped modes is also studied. A frequency band gap depends on the radius of a bulge and is independent of its width. The obtained results can be extended to analyze bound states in quantum wires. PMID- 27281285 TI - Tunable Lamb wave band gaps in two-dimensional magnetoelastic phononic crystal slabs by an applied external magnetostatic field. AB - This paper theoretically investigates the band gaps of Lamb mode waves in two dimensional magnetoelastic phononic crystal slabs by an applied external magnetostatic field. With the assumption of uniformly oriented magnetization, an equivalent piezomagnetic material model is used. The effects of magnetostatic field on phononic crystals are considered carefully in this model. The numerical results indicate that the width of the first band gap is significantly changed by applying the external magnetic field with different amplitude, and the ratio between the maximum and minimum gap widths reaches 228%. Further calculations demonstrate that the orientation of the magnetic field obviously affects the width and location of the first band gap. The contactless tunability of the proposed phononic crystal slabs shows many potential applications of vibration isolation in engineering. PMID- 27281286 TI - Three-Quarters of Persons in the US Population Reporting a Clinical Diagnosis of Fibromyalgia Do Not Satisfy Fibromyalgia Criteria: The 2012 National Health Interview Survey. AB - OBJECTIVES: Although fibromyalgia criteria have been in effect for decades, little is known about how the fibromyalgia diagnosis is applied and understood by clinicians and patients. We used the National Health Interview Survey (NHIS) to determine the prevalence of self-reported clinician diagnosed fibromyalgia and then compared demographics, symptoms, disability and medical utilization measures of persons with a clinical diagnosis of fibromyalgia that did not meet diagnostic criteria (false-positive or prior [F/P] fibromyalgia) to persons with and without criteria-positive fibromyalgia. METHODS: The National Health Interview Survey (NHIS) collected information about both clinical diagnosis and symptoms of fibromyalgia that was appropriately weighted to represent 225,726,257 US adults. Surrogate NHIS diagnostic criteria for fibromyalgia were developed based on the level of polysymptomatic distress (PSD) as characterized in the 2011 modified American College of Rheumatology criteria (ACR) for fibromyalgia. Persons with F/P fibromyalgia were compared with persons who do not have fibromyalgia and those meeting surrogate NHIS fibromyalgia criteria. RESULTS: Of the 1.78% of persons reporting a clinical diagnosis, 73.5% did not meet NHIS fibromyalgia criteria. The prevalence of F/P fibromyalgia is 1.3%. F/P fibromyalgia is associated with a mild degree of polysymptomatic distress (NHIS PSD score 6.2) and characterized by frequent but not widespread pain and insomnia. Measures of work disability and medical utilization in F/P fibromyalgia were equal to that seen with NHIS criteria positive fibromyalgia and were 6-7x greater in F/P fibromyalgia than in non-fibromyalgia persons. F/P fibromyalgia was best predicted by being female (Odds Ratio [OR] 8.81), married (OR 3.27), and white (OR 1.96). In contrast, being a white, married woman was only modestly predictive of NHIS (criteria positive) fibromyalgia (OR 2.1). CONCLUSIONS: The majority of clinically diagnosed fibromyalgia cases in the US do not reach levels of severity necessary and sufficient for diagnosis. The clinical diagnosis of fibromyalgia is disproportionally dependent on demographic and social factors rather than the symptoms themselves. Diagnostic criteria for fibromyalgia appear to be used as a vague guide by clinicians and patients, and allow for substantial diagnostic expansion of fibromyalgia. PMID- 27281288 TI - Direct Measurement of Pore Dynamics and Leakage Induced by a Model Antimicrobial Peptide in Single Vesicles and Cells. AB - Antimicrobial peptides are promising therapeutic alternatives to counter growing antimicrobial resistance. Their precise mechanism of action remains elusive, however, particularly with respect to live bacterial cells. We investigated the interaction of a fluorescent melittin analogue with single giant unilamellar vesicles, giant multilamellar vesicles, and bilamellar Gram-negative Escherichia coli (E. coli) bacteria. Time-lapse fluorescence lifetime imaging microscopy was employed to determine the population distribution of the fluorescent melittin analogue between pore state and membrane surface state, and simultaneously measure the leakage of entrapped fluorescent species from the vesicle (or bacterium) interior. In giant unilamellar vesicles, leakage from vesicle interior was correlated with an increase in level of pore states, consistent with a stable pore formation mechanism. In giant multilamellar vesicles, vesicle leakage occurred more gradually and did not appear to correlate with increased pore states. Instead pore levels remained at a low steady-state level, which is more in line with coupled equilibria. Finally, in single bacterial cells, significant increases in pore levels were observed over time, which were correlated with only partial loss of cytosolic contents. These observations suggested that pore formation, as opposed to complete dissolution of membrane, was responsible for the leakage of contents in these systems, and that the bacterial membrane has an adaptive capacity that resists peptide attack. We interpret the three distinct pore dynamics regimes in the context of the increasing physical and biological complexity of the membranes. PMID- 27281287 TI - Cognition and the Default Mode Network in Children with Sickle Cell Disease: A Resting State Functional MRI Study. AB - Cerebrovascular complications are frequent events in children with sickle cell disease, yet routinely used techniques such as Transcranial Doppler (TCD), Magnetic Resonance (MRI) and Angiography (MRA), insufficiently explain the cause of poor cognitive performances. Forty children with SS-Sbeta degrees (mean age 8 years) underwent neurocognitive evaluation and comprehensive brain imaging assessment with TCD, MRI, MRA, Resting State (RS) Functional MRI with evaluation of the Default Mode Network (DMN). Sixteen healthy age-matched controls underwent MRI, MRA and RS functional MRI.Children with SCD display increased brain connectivity in the DMN even in the absence of alterations in standard imaging techniques. Patients with low neurocognitive scores presented higher brain connectivity compared to children without cognitive impairment or controls, suggesting an initial compensatory mechanism to maintain performances. In our cohort steady state haemoglobin level was not related to increased brain connectivity, but SatO2<97% was. Our findings provide novel evidence that SCD is characterized by a selective disruption of connectivity among relevant regions of the brain, potentially leading to reduced cognition and altered functional brain dynamics. RS functional MRI could be used as a useful tool to evaluate cognition and cerebral damage in SCD in longitudinal trials. PMID- 27281290 TI - Effect of the Mn Oxidation State on Single-Molecule-Magnet Properties: Mn(III) vs Mn(IV) in Biologically Inspired DyMn3O4 Cubanes. AB - Inspired by the ferromagnetic coupling in the cubane model CaMn(IV)3O4 of the oxygen-evolving complex of photosystem II, 3d-4f mixed-metal DyMn3O4 clusters were prepared for investigation of the magnetic properties. For comparison, YMn(IV)3O4 and YMn(IV)2Mn(III)O4 clusters were investigated as well and showed ferromagnetic interactions, like the calcium analogue. DyMn(IV)3O4 displays single-molecule-magnet properties, while the one-electron-reduced species (DyMn(IV)2Mn(III)O4) does not, despite the presence of a Mn(III) center with higher spin and single-ion anisotropy. PMID- 27281291 TI - Response Characteristics of Bisphenols on a Metal-Organic Framework-Based Tyrosinase Nanosensor. AB - Bisphenols (BPs), which have more than ten kinds of structural analogues, are emerging as the most important endocrine disrupting chemicals that adversely affect human health and aquatic life. A tyrosinase nanosensor based on metal organic frameworks (MOFs) and chitosan was developed to investigate the electrochemical response characteristics and mechanisms of nine kinds of BPs for the first time. The developed tyrosinase nanosensor showed a sensitive response to bisphenol A, bisphenol F, bisphenol E, bisphenol B, and bisphenol Z, and the responsive sensitivities were highly dependent on their respective log Kow values. However, the nanosensor showed no response to bisphenol S (BPS), bisphenol AP (BPAP), bisphenol AF (BPAF), or tetrabromobisphenol A, although BPS, BPAP, and BPAF have structures similar to those of the responsive BPs. The obtained results reveal that the electrochemical response of different BPs is affected not only by the molecular structure, especially the available ortho positions of phenolic hydroxyl groups, but also by the substituent group properties (electron acceptor or electron donor) on the bisphenol framework. The electronic cloud distribution of the phenolic hydroxyl groups, which is affected by the substituent group, determines whether the available ortho positions of phenolic hydroxyl groups can be oxidized by the tyrosinase biosensor. These response mechanisms are very significant as they can be used for predicting the response characteristics of many BPs and their various derivatives and metabolites on biosensors. The unexpected anti-interference ability of the biosensor to nine heavy metal ions was also discovered and discussed. The MOF chitosan nanocomposite proves to be a promising sensing platform for the construction of diverse biosensors for selective detection of targets even in the presence of a high concentration of heavy metal ions. PMID- 27281292 TI - Exogenous Melatonin Treatment Increases Chilling Tolerance and Induces Defense Response in Harvested Peach Fruit during Cold Storage. AB - The effect of exogenous melatonin on chilling injury in peach fruit after harvest was investigated. To explore the optimum concentration of melatonin for chilling tolerance induction, peach fruit were treated with 50, 100, or 200 MUM melatonin for 120 min and then stored for 28 days at 4 degrees C. The results showed that application of melatonin at 100 MUM was most effective in reducing chilling injury of peach fruit after harvest. Peaches treated with melatonin at this concentration displayed higher levels of extractable juice rate and total soluble solids than the non-treated peaches. In addition, melatonin treatment enhanced expression of PpADC, PpODC, and PpGAD and consequently increased polyamines and gamma-aminobutyric acid (GABA) contents. Meanwhile, the upregulated transcripts of PpADC and PpODC and inhibited PpPDH expression resulted in the higher proline content in melatonin-treated fruit compared to the control fruit. Our results revealed that melatonin treatment may be a useful technique to alleviate chilling injury in cold-stored peach fruit. The chilling tolerance of harvested peaches induced by melatonin treatment is associated with higher levels of polyamine, GABA, and proline. These data provided here are the first protective evidence of exogenous melatonin in harvested horticultural products in response to direct chilling stress. PMID- 27281293 TI - Intuitive and Deliberative Empathizers and Systemizers. AB - OBJECTIVE: Recent findings suggest there may be some overlap between individual differences in orientations for intuitive thinking and empathizing, and between deliberative thinking and systemizing. This overlap is surprising, given that intuitive and deliberative thinking derive from dual-process theories that concern domain-general types of processing, whereas theoretically, empathizing and systemizing are domain-specific orientations for understanding people and lawful physical phenomena. METHOD: The present studies (Study 1: N = 2,789, Study 2: N = 87; Finnish volunteers ages 15-69, 65% females) analyzed each of these four constructs using self-report as well as performance measures. RESULTS: Confirmatory factor analysis showed that systemizing was strongly and positively related to deliberative thinking and negatively related to intuitive thinking. Empathizing was negatively related to deliberative thinking, whereas no association between empathizing and intuition was found. However, some deliberative aspects and some intuitive aspects were involved in empathizing. CONCLUSIONS: The findings indicate that a distinction between "intuitive empathizing" and "deliberative systemizing" is not warranted. PMID- 27281295 TI - Iron Acquisition Pathways as Targets for Antitubercular Drugs. AB - Tuberculosis nowadays ranks as the second leading cause of death from an infectious disease worldwide. In the last twenty years, this disease has again started to spread mainly for the appearance of multi-drug resistant forms. Therefore, new targets are needed to address the growing emergence of bacterial resistance and for antitubercular drug development. Efficient iron acquisition is crucial for the pathogenesis of Mycobacterium tuberculosis, because it serves as cofactor in many essential biological processes, including DNA biosynthesis and cellular respiration. Bacteria acquire iron chelating non-heme iron from the host using the siderophore mycobactins and carboxymycobactins and by the uptake of heme iron released by damaged red blood cells, through several acquisition systems. Drug discovery focused its efforts on the inhibition of MbtI and MbtA, which are are two enzymes involved in the mycobactin biosynthetic pathway. In particular, MbtI inhibitors have been studied in vitro, while MbtA inhibitors showed activity also in infected mice. Another class of compounds, MmpL3 inhibitors, showed antitubercular activity in vitro and in vivo, but their mechanism of action seems to be off-target. Some compounds inhibiting 4' phosphopantetheinyl transferase were discovered but not tested on in vivo assays. The available data reported in this study based on inhibitors and gene deletion studies, suggest that targeting iron acquisition systems could be considered a promising antitubercular strategy. Due to their redundancy, the relative importance of each pathway for Mycobacterium tuberculosis survival has still to be determined. Thus, in vivo studies with new, potent and specific inhibitors are needed to highlight target selection. PMID- 27281296 TI - Engineered Zinc Oxide Nanoparticles; Biological Interactions at the Organ Level. AB - Zinc oxide nanoparticles (ZnO NPs) are one of the widely used nanoparticles with spectrum of application, in the areas like daily care products, sensors, antibacterial agents, and biomedical sector. With extensive application the risk of exposure at occupational and consumer level also increases. Huge amount of data are available on the biointeraction of ZnO NPs. Though the toxicity of ZnO NPs is attributed to particle dissolution inside the cellular compartments and their ability to generate the reactive oxygen species, the ambiguity prevails over the exact mechanism of toxicity. The in vivo studies on different animal models and humans suggest different level of toxicity in these organisms. However the synthetic route, physiochemical properties of the nanoparticle, mode of exposure and nature of the test system often influences these studies. Hence the study results vary and sometimes contradict on one another. The current review focuses on the interaction of ZnO NPs with different organ systems. It also points to the factors to be considered while undertaking such studies in order to ensure reliability of the results. PMID- 27281297 TI - Human Tuberculosis I. Epidemiology, Diagnosis and Pathogenetic Mechanisms. AB - Mycobacterium tuberculosis (M. tuberculosis), an almost genetically monomorphic pathogen is a human parasite, transmitted mostly by humans and causes tuberculosis (TB). TB is firmly associated to poverty, although lack of proper nutrition and lowered immune status are contributing factors for disease development. TB remains second only to HIV/AIDS as the leading cause of mortality worldwide due to a single infectious agent and is responsible for nearly 1.5 million deaths annually. Some steps of the progress of our knowledge of M. tuberculosis physiology and its interactions with human beings, are reviewed here. This progress has provided fertile ground for improving diagnosis and cure of TB infection. For TB diagnostics laboratories in high-burden countries, primary isolation is the first step before performing drug susceptibility testing (DST) of M. tuberculosis. IGRA (interferon-gamma release assay)-based tests for diagnosis of active TB are sufficiently fast, specific and sensitive to allow to contain infection and distinguish among latent TB infection and BCG vaccination individuals from those who have clinically resolved M. tuberculosis infection after anti-TB treatment. PMID- 27281298 TI - The Complete Mechanism of an Aldol Condensation. AB - Although aldol condensation is one of the most important organic reactions, capable of forming new C-C bonds, its mechanism has never been fully established. We now conclude that the rate-limiting step in the base-catalyzed aldol condensation of benzaldehydes with acetophenones, to produce chalcones, is the final loss of hydroxide and formation of the C?C bond. This conclusion is based on a study of the partitioning ratios of the intermediate ketols and on the solvent kinetic isotope effects, whereby the condensations are faster in D2O than in H2O, regardless of substitution. PMID- 27281299 TI - Glucose-Derived Carbonaceous Nanospheres for Photoacoustic Imaging and Photothermal Therapy. AB - Carbon nanomaterials with small size and unique optical properties have attracted intensive interest for their promising biomedical applications. In this work, glucose-derived carbonaceous nanospheres (CNSs) with high photothermal conversion efficiency up to 35.1% are explored for the first time as a novel carbon-based theranostic agent. Different from most other carbon nanomaterials, the obtained CNSs are highly biocompatible and nontoxic because of their intrinsic hydrophilic property and the use of glucose as raw materials. Under near-infrared laser irradiation (808 nm, 6 W cm(-2)) for 10 min, less than 15% of PC-3M-IE8 cells exposed to CNSs aqueous dispersions (0.16 mg/mL) remained alive. After intravenous administration of CNSs aqueous dispersions into nude mice, the photoacoustic intensity of the tumor region is about 2.5 times higher than that of preinjection. These results indicate that CNSs are suitable for simultaneous photoacoustic imaging and photothermal ablation of cancer cells and can serve as promising biocompatible carbon-based agents for further clinical trials. PMID- 27281301 TI - Issues in the Diagnosis and Management of Hereditary Antithrombin Deficiency. AB - OBJECTIVE: To review insights gained in the past several years about hereditary antithrombin (AT) deficiency and to outline approaches to the management of patients with AT deficiency in the acute and chronic settings. DATA SOURCES: An extensive literature search of Scopus (January 2008-April 2016) was performed for the terms congenital antithrombin deficiency, inherited antithrombin deficiency, or hereditary antithrombin deficiency Additional references were identified by reviewing literature citations. STUDY SELECTION: All relevant English-language case reports, reviews, clinical studies, meeting abstracts, and book chapters assessing hereditary AT deficiency were included. DATA SYNTHESIS: AT deficiency significantly increases the risk of venous thromboembolism (VTE). The risk of VTE is particularly high during pregnancy, the postpartum period, and following major surgery. Effective clinical management includes determination of the appropriate type and duration of antithrombotic therapy (ie, AT replacement for acute situations) while minimizing the risk of bleeding. For persons newly diagnosed with AT deficiency, age, lifestyle, concurrent medical conditions, family history, and personal treatment preferences can be used to individualize patient management. Patients should be informed of the risks associated with hormonal therapy, pregnancy, surgical procedures, and immobility, which further increase the risk of VTE in patients with AT deficiency. CONCLUSION: AT deficiency poses the highest risk for VTE among the hereditary thrombophilias, often requiring long-term anticoagulation. Undertaking an evaluation for hereditary thrombophilia is controversial; however, a diagnosis of VTE in association with AT deficiency can have management implications. An important treatment option for patients with this disorder in high-risk situations is AT concentrate. PMID- 27281300 TI - A small peptide promotes EphA2 kinase-dependent signaling by stabilizing EphA2 dimers. AB - BACKGROUND: The EphA2 receptor tyrosine kinase is known to promote cancer cell malignancy in the absence of activation by ephrin ligands. This behavior depends on high EphA2 phosphorylation on Ser897 and low tyrosine phosphorylation, resulting in increased cell migration and invasiveness. We have previously shown that EphA2 forms dimers in the absence of ephrin ligand binding, and that dimerization of unliganded EphA2 can decrease EphA2 Ser897 phosphorylation. We have also identified a small peptide called YSA, which binds EphA2 and competes with the naturally occurring ephrin ligands. METHODS: Here, we investigate the effect of YSA on EphA2 dimer stability and EphA2 function using quantitative FRET techniques, Western blotting, and cell motility assays. RESULTS: We find that the YSA peptide stabilizes the EphA2 dimer, increases EphA2 Tyr phosphorylation, and decreases both Ser897 phosphorylation and cell migration. CONCLUSIONS: The experiments demonstrate that the small peptide ligand YSA reduces EphA2 Ser897 pro-tumorigenic signaling by stabilizing the EphA2 dimer. GENERAL SIGNIFICANCE: This work is a proof-of-principle demonstration that EphA2 homointeractions in the plasma membrane can be pharmacologically modulated to decrease the pro tumorigenic signaling of the receptor. PMID- 27281302 TI - A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study. AB - BACKGROUND: To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. OBJECTIVES: We compared the effects of EPA supplementation with those of DHA supplementation (re esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. DESIGN: In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. RESULTS: Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% +/- 2.8% compared with -0.5% +/- 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% +/- 1.6% compared with -1.2% +/- 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% +/- 5.0% compared with -1.8% +/- 6.5%, respectively; P = 0.25), IL-6 (-12.0% +/- 7.0% compared with -13.4% +/- 7.0%, respectively; P = 0.86), and tumor necrosis factor-alpha (-14.8% +/- 5.1% compared with -7.6% +/- 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% +/- 2.3% compared with -11.9% +/- 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% +/- 1.3% compared with 0.3% +/- 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% +/- 1.4% compared with -0.7% +/- 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% +/- 1.8% compared with 2.2% +/- 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment * sex interaction = 0.046). CONCLUSIONS: DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003. PMID- 27281304 TI - A weight-loss program adapted to the menstrual cycle increases weight loss in healthy, overweight, premenopausal women: a 6-mo randomized controlled trial. AB - BACKGROUND: Hormonal fluctuations during the menstrual cycle influence energy intake and expenditure as well as eating preferences and behavior. OBJECTIVE: We examined the effect in healthy, overweight, premenopausal women of a diet and exercise weight-loss program that was designed to target and moderate the effects of the menstrual cycle compared with the effect of simple energy restriction. DESIGN: A total of 60 healthy, overweight, premenopausal women were included in a 6-mo weight-loss program in which each subject consumed a diet of 1600 kcal/d. Subjects were randomly assigned to either a combined diet and exercise program that was tailored to metabolic changes of the menstrual cycle (Menstralean) or to undergo simple energy restriction (control). RESULTS: Thirty-one women (19 Menstralean and 12 control women) completed the study [mean +/- SD body mass index (in kg/m(2)): 32.0 +/- 5.2]. Both groups lost weight during the study. In an intention-to-treat analysis, the Menstralean group did not achieve a clinically significant weight loss compared with that of the control group (P = 0.61). In per-protocol analyses, a more-pronounced weight loss of 4.3 +/- 1.4 kg (P = 0.002) was shown in adherent Menstralean subjects than in the control group. CONCLUSION: A differentiated diet and exercise program that is tailored to counteract food cravings and metabolic changes throughout the menstrual cycle may increase weight loss above that achieved with a traditional diet and exercise program in women who can comply with the program. This trial was registered at clinicaltrials.gov as NCT01622114. PMID- 27281303 TI - The association of serum choline with linear growth failure in young children from rural Malawi. AB - BACKGROUND: Choline is an essential nutrient for cell structure, cell signaling, neurotransmission, lipid transport, and bone formation. Choline can be irreversibly converted to betaine, a major source of methyl groups. Trimethylene N-oxide (TMAO), a proatherogenic molecule, is produced from the metabolism of dietary choline by the gut microbiome. The relation between serum choline and its closely related metabolites with linear growth in children is unknown. OBJECTIVE: The aim was to characterize the relation between serum choline and its closely related metabolites, betaine and TMAO, with linear growth and stunting in young children. DESIGN: We measured serum choline, betaine, and TMAO concentrations by using liquid chromatography isotopic dilution tandem mass spectrometry in a cross sectional study in 325 Malawian children, aged 12-59 mo, of whom 62% were stunted. RESULTS: Median (25th, 75th percentile) serum choline, betaine, and TMAO concentrations were 6.4 (4.8, 8.3), 12.4 (9.1, 16.3), and 1.2 (0.7, 1.8) MUmol/L, respectively. Spearman correlation coefficients of age with serum choline, betaine, and TMAO were -0.57 (P < 0.0001), -0.26 (P < 0.0001), and -0.10 (P = 0.07), respectively. Correlation coefficients of height-for-age z score with serum choline, betaine-to-choline ratio, and TMAO-to-choline ratio were 0.31 (P < 0.0001), -0.24 (P < 0.0001), and -0.29 (P < 0.0001), respectively. Serum choline concentrations were strongly and significantly associated with stunting. Children with and without stunting had median (25th, 75th percentile) serum choline concentrations of 5.6 (4.4, 7.4) and 7.3 (5.9, 9.1) MUmol/L (P < 0.0001). CONCLUSIONS: Linear growth failure in young children is associated with low serum choline and elevated betaine-to-choline and TMAO-to-choline ratios. Further work is needed to understand whether low dietary choline intake explains low circulating choline among stunted children living in low-income countries and whether increasing choline intake may correct choline deficiency and improve growth and development. This trial was registered in the ISRCTN registry (www.isrctn.com) as ISRCTN14597012. PMID- 27281305 TI - Empty calories and phantom fullness: a randomized trial studying the relative effects of energy density and viscosity on gastric emptying determined by MRI and satiety. AB - BACKGROUND: Stomach fullness is a determinant of satiety. Although both the viscosity and energy content have been shown to delay gastric emptying, their relative importance is not well understood. OBJECTIVE: We compared the relative effects of and interactions between the viscosity and energy density on gastric emptying and perceived satiety. DESIGN: A total of 15 healthy men [mean +/- SD age: 22.6 +/- 2.4 y; body mass index (in kg/m(2)): 22.6 +/- 1.8] participated in an experiment with a randomized 2 * 2 crossover design. Participants received dairy-based shakes (500 mL; 50% carbohydrate, 20% protein, and 30% fat) that differed in viscosity (thin and thick) and energy density [100 kcal (corresponding to 0.2 kcal/mL) compared with 500 kcal (corresponding to 1 kcal/mL)]. After ingestion, participants entered an MRI scanner where abdominal scans and oral appetite ratings on a 100-point scale were obtained every 10 min until 90 min after ingestion. From the scans, gastric content volumes were determined. RESULTS: Overall, the gastric emptying half-time (GE t50) was 54.7 +/ 3.8 min. The thin 100-kcal shake had the lowest GE t50 of 26.5 +/- 3.0 min, followed by the thick 100-kcal shake with a GE t50 of 41 +/- 3.9 min and the thin 500-kcal shake with a GE t50 of 69.5 +/- 5.9 min, and the thick 500-kcal shake had the highest GE t50 of 81.9 +/- 8.3 min. With respect to appetite, the thick 100-kcal shake led to higher fullness (58 points at 40 min) than the thin 500 kcal shake (48 points at 40 min). CONCLUSIONS: Our results show that increasing the viscosity is less effective than increasing the energy density in slowing gastric emptying. However, the viscosity is more important to increase the perceived fullness. These results underscore the lack of the satiating efficiency of empty calories in quickly ingested drinks such as sodas. The increase in perceived fullness that is due solely to the increased viscosity, which is a phenomenon that we refer to as phantom fullness, may be useful in lowering energy intake. This trial was registered at www.trialregister.nl as NTR4573. PMID- 27281306 TI - Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and risk of type 2 diabetes in Scandinavian men and women. AB - BACKGROUND: Studies that use dietary biomarkers to investigate the association between whole-grain intake and the risk of developing type 2 diabetes (T2D) are lacking. OBJECTIVE: We examined the association between plasma total alkylresorcinols and the alkylresorcinol C17:0-to-C21:0 ratio, biomarkers of whole-grain wheat and rye intake and relative whole-grain rye over whole-grain wheat intake, respectively, and the risk of T2D among Scandinavian men and women. DESIGN: A nested case-control study was established within the Northern Sweden Health and Disease Study and the Danish Diet, Cancer and Health cohort. Alkylresorcinol concentrations and the ratios of C17:0 to C21:0 were determined in plasma samples from 931 case-control pairs. ORs for T2D were calculated for plasma total alkylresorcinol concentration or C17:0-to-C21:0 ratio in quartiles with the use of conditional logistic regression that was adjusted for potential confounders. Additional analyses with whole-grain wheat and rye intake estimated from food-frequency questionnaires (FFQs) as exposures were also performed. RESULTS: The plasma total alkylresorcinol concentration was not associated with T2D risk (OR: 1.34; 95% CI: 0.95, 1.88) for the highest compared with the lowest quartiles in multivariable adjusted models. However, the C17:0-to-C21:0 ratio was associated with a lower diabetes risk (OR: 0.54; 95% CI: 0.37, 0.78). Analyses with whole-grain intake estimated from FFQs yielded similar results. CONCLUSIONS: Total whole-grain wheat and rye intake, reflected by alkylresorcinols in plasma, was not associated with a lower risk of T2D in a population with high whole-grain intake. In contrast, the proportion of whole-grain rye to whole-grain wheat intake, indicated by the plasma C17:0-to-C21:0 ratio, was inversely associated with T2D. This suggests that whole-grain intake dominated by rye may be favorable for T2D prevention. PMID- 27281307 TI - Dietary phosphatidylcholine and risk of all-cause and cardiovascular-specific mortality among US women and men. AB - BACKGROUND: The trimethylamine-containing nutrient phosphatidylcholine is the major dietary source for the gut microbiota metabolite trimethylamine-N-oxide (TMAO), which has been related to cardiovascular diseases (CVDs) and mortality. Previous research suggested that the relation of TMAO with CVD risk might be stronger in diabetic than in nondiabetic populations. However, the evidence for an association of dietary phosphatidylcholine with CVD and mortality is limited. OBJECTIVES: We aimed to examine whether dietary consumption of phosphatidylcholine, which is mainly derived from eggs, red meat, and fish, is related to all-cause and CVD mortality in 2 cohorts of US women and men. In particular, we also tested if such an association was modified by diabetes status. DESIGN: We followed 80,978 women from the Nurses' Health Study (1980 2012) and 39,434 men from the Health Professionals Follow-Up Study (1986-2012), who were free of cancer and CVD at baseline, for mortality. Dietary intakes and potential confounders were assessed with regularly administered questionnaires. We used Cox proportional hazards models to estimate HRs and 95% CIs. RESULTS: We documented 17,829 all-cause and 4359 CVD deaths during follow-up. After multivariate adjustment for potential confounders, including demographic factors, disease status, lifestyle, and dietary intakes, higher phosphatidylcholine intakes were associated with an increased risk of all-cause and CVD mortality. HRs (95% CIs) comparing the top and bottom quintiles of phosphatidylcholine intake were 1.11 (1.06, 1.17; P-trend across quintiles < 0.0001) for all-cause mortality and 1.26 (1.15, 1.39; P-trend < 0.0001) for CVD mortality in the combined data of both cohorts. The associations of phosphatidylcholine with all cause and CVD mortality were stronger in diabetic than in nondiabetic participants (P-interaction = 0.0002 and 0.001, respectively). CONCLUSION: These data suggest that higher phosphatidylcholine consumption is associated with increased all-cause and CVD mortality in the US population, especially in patients with diabetes, independent of traditional risk factors. PMID- 27281308 TI - Genetic susceptibility to diabetes and long-term improvement of insulin resistance and beta cell function during weight loss: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. AB - BACKGROUND: Diet interventions have shown effectiveness in improving diabetes risk factors; however, little is known about whether the effects of diet intervention are different according to genetic susceptibility. OBJECTIVE: We examined interactions between weight-loss diets and the genetic risk score (GRS) for diabetes on 2-y changes in markers of insulin resistance and beta cell function in a randomized controlled trial. DESIGN: Data from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial were analyzed. A GRS was calculated on the basis of 31 diabetes-associated variants in 744 overweight or obese nondiabetic adults (80% white Americans). We assessed the changes in insulin resistance and beta cell function over the 2-y intervention. RESULTS: Dietary protein significantly interacted with the diabetes GRS on fasting insulin, glycated hemoglobin (HbA1c), the homeostasis model assessment of beta cell function (HOMA-B), and the homeostasis model assessment of insulin resistance (HOMA-IR) at 2 y in white Americans (P-interaction = 0.02, 0.04, 0.01, and 0.05, respectively). The lower GRS was associated with a greater decrease in fasting insulin (P = 0.04), HbA1c (P = 0.0001), and HOMA-IR (P = 0.02), and a lesser increase in HOMA-B (P = 0.004) in participants consuming a low-protein diet. Participants with a higher GRS might have a greater reduction in fasting insulin when consuming a high-protein diet (P = 0.03). CONCLUSIONS: Our data suggest that individuals with a lower genetic risk of diabetes may benefit more from consuming a low-protein weight-loss diet in improving insulin resistance and beta cell function, whereas a high-protein diet may be more beneficial for white patients with a higher genetic risk. This trial was registered at clinicaltrials.gov as NCT00072995. PMID- 27281310 TI - Food quality score and the risk of coronary artery disease: a prospective analysis in 3 cohorts. AB - BACKGROUND: Currently, there are few diet quality assessment tools that are predictive of coronary artery disease (CAD) risk that do not require nutrient analysis and substantial time to administer in clinical settings. OBJECTIVE: To inform the development of such a tool, we prospectively examined the association between a food-based diet quality score and risk of CAD in 3 separate large US cohort studies. DESIGN: Between 1984 and 2012, 71,415 women (aged 43-63 y in 1984), 42,945 men (aged 40-75 y in 1986), and 93,131 younger women (aged 27-44 y in 1991) without a history of cardiovascular disease were followed up to 28 y. Diet was assessed <=7 times by using repeated food-frequency questionnaires. We computed the Food Quality Score (FQS) for each individual based on food groups previously associated with less weight gain. A higher score represented a healthier diet. The FQS and CAD association was modeled with the Cox proportional hazard model, controlling for potential confounders. We also compared the magnitude of association with CAD for the FQS and other diet quality scores. RESULTS: We ascertained 6817 incident total CAD events, with 4588 cases of nonfatal myocardial infarction and 2131 fatal CAD events. Comparing top to bottom deciles, pooled RRs of the FQS were 0.61 (95% CI: 0.54, 0.69; P-trend < 0.001) for total CAD. These associations were independent of established cardiovascular disease risk factors including body weight, physical activity, and smoking. The magnitude of the RR for 1 SD of the FQS and CAD was generally similar to established diet scores that require detailed nutrient analysis, including the Alternate Healthy Eating Index-2010, the Dietary Approaches to Stop Hypertension score, and the alternate Mediterranean diet score. CONCLUSION: A higher food based diet quality score was associated with lower risk of CAD and was comparable with established diet scores. PMID- 27281311 TI - Risk Factors of Typhoid Infection in the Indonesian Archipelago. AB - BACKGROUND: Knowledge of risk factors and their relative importance in different settings is essential to develop effective health education material for the prevention of typhoid. In this study, we examine the effect of household level and individual behavioural risk factors on the risk of typhoid in three Indonesian islands (Sulawesi, Kalimantan and Papua) in the Eastern Indonesian archipelago encompassing rural, peri-urban and urban areas. METHODS: We enrolled 933 patients above 10 years of age in a health facility-based case-control study between June 2010 and June 2011. Individuals suspected of typhoid were tested using the typhoid IgM lateral flow assay for the serodiagnosis of typhoid fever followed by blood culture testing. Cases and controls were defined post recruitment: cases were individuals with a culture or serology positive result (n = 449); controls were individuals negative to both serology and culture, with or without a diagnosis other than typhoid (n = 484). Logistic regression was used to examine the effect of household level and individual level behavioural risk factors and we calculated the population attributable fraction (PAF) of removing each risk significant independent behavioural risk factor. RESULTS: Washing hands at critical moments of the day and washing hands with soap were strong independent protective factors for typhoid (OR = 0.38 95% CI 0.25 to 0.58 for each unit increase in hand washing frequency score with values between 0 = Never and 3 = Always; OR = 3.16 95% CI = 2.09 to 4.79 comparing washing hands with soap sometimes/never vs. often). These effects were independent of levels of access to water and sanitation. Up to two thirds of cases could be prevented by compliance to these practices (hand washing PAF = 66.8 95% CI 61.4 to 71.5; use of soap PAF = 61.9 95%CI 56.7 to 66.5). Eating food out in food stalls or restaurant was an important risk factor (OR = 6.9 95%CI 4.41 to 10.8 for every unit increase in frequency score). CONCLUSIONS: Major gains could potentially be achieved in reducing the incidence of typhoid by ensuring adherence to adequate hand-washing practices alone. This confirms that there is a pivotal role for 'software' related interventions to encourage behavior change and create demand for goods and services, alongside development of water and sanitation infrastructure. PMID- 27281309 TI - Serum 25-hydroxyvitamin D concentration is inversely associated with mucosal inflammation in patients with ulcerative colitis. AB - BACKGROUND: Vitamin D exerts anti-inflammatory actions both in vitro and in murine models of colitis. In previous studies, we demonstrated that vitamin D protects against the development of colitis by maintaining the integrity of the intestinal mucosal barrier. OBJECTIVE: We sought to evaluate whether deficient serum 25 hydroxyvitamin D [25(OH)D] concentrations are associated with increased mucosal inflammation, a loss of epithelial junctional proteins, and an increase in mucosal inflammatory cytokines in patients with ulcerative colitis (UC). DESIGN: We prospectively enrolled 230 subjects with UC. Serum 25(OH)D concentrations were compared with the Mayo endoscopic score, the total Mayo score, and histologic activity. Colonic mucosal expression concentrations of vitamin D receptor (VDR), E-cadherin, zonula occluden 1 (ZO-1), occludin, claudin 2, tumor necrosis factor alpha (TNF-alpha), and interleukin 8 (IL-8) were compared between dichotomous groups with low or high serum 25(OH)D concentrations. RESULTS: The mean serum 25(OH)D concentration was 21.8 ng/mL. Subjects stratified by concentrations included 12.6% >=30 ng/mL, 45.6% >=20 to <30 ng/mL, 37.4% >=10 to <20 ng/mL, and 4.4% <10 ng/mL. There was an inverse association between serum 25(OH)D concentrations and mucosal inflammation as assessed by the Mayo endoscopy score (P = 0.01), disease activity as indicated by the total Mayo score (P = 0.001), and histologic activity (P = 0.02). A serum 25(OH)D concentration <20 ng/mL was associated with decreased mucosal transcript and protein expression concentrations of VDR, E-cadherin, and occludin as well as decreased protein expression of ZO-1, whereas TNF-alpha and IL-8 mucosal transcript expression concentrations were increased. CONCLUSIONS: In UC patients, serum 25(OH)D concentration is inversely correlated with mucosal inflammation and disease activity. These results, coupled with the findings that serum 25(OH)D concentrations correlate with the mucosal expression of VDR as well as epithelial junction proteins and inversely with proinflammatory cytokines, suggest that vitamin D deficiency may contribute to UC inflammation by disrupting epithelial barrier function. PMID- 27281312 TI - Intrinsic Subgroups or Individual Biomarkers for Predicting Outcome of Metastatic Breast Cancer? PMID- 27281313 TI - Modeling the effects of water content on TiO2 nanoparticles transport in porous media. AB - The transport of manufactured titanium dioxide (TiO2, rutile) nanoparticles (NP) in porous media was investigated by metric scale column experiments under different water saturation and ionic strength (IS) conditions. The NP breakthrough curves showed that TiO2 NP retention on the interface between air and water (AWI) and the interface between the solid and the fluid (SWI) is insignificant for an IS equal to or smaller than 3mM KCl. For larger IS, the retention is depending on the water content and the fluid velocity. The experiments, conducted with an IS of 5mM KCl, showed a significantly higher retention of NP than that observed under saturated conditions and very similar experimental conditions. Water flow was simulated using the standard Richards equation. The hydrodynamic model parameters for unsaturated flow were estimated through independent drainage experiments. A new mathematical model was developed to describe TiO2 NP transport and retention on SWI and AWI. The model accounts for the variation of water content and water velocity as a function of depth and takes into account the presence of the AWI and its role as a NP collector. Comparisons with experimental data showed that the suggested modeled processes can be used to quantify the NPs retentions at the AWI and SWI. The suggested model can be used for both saturated and unsaturated conditions and for a rather large range of velocities. PMID- 27281315 TI - Combined Palmer Type 1A and 1B Traumatic Lesions of the Triangular Fibrocartilage Complex A New Category. AB - We present a series of eight patients who underwent wrist arthroscopy for presumed solitary tears of the triangular fibrocartilage (TFC) and were, instead, found to have combined 1A (central tear) and 1B (ulnar avulsion) tears. The Palmer Classification does not currently categorize this combined pattern. All but one patient had a traumatic injury. Each subject had preoperative radiographs and MRI scans. TFC tears were evident on all MRI scans, though only one was suggestive of a combined tear pat - tern. Surgical management included arthroscopic central tear debridement and ulnar peripheral repair. Average follow up was 22 months. Grip strength in the affected hand improved from 16% deficit as compared to the unaffected side, to 3.5% deficit postoperatively (p = 0.003), and visual analog scores (VAS) decreased from an average of 7.1/10 preoperatively to 2.3/10 postoperatively (p < 0.001). There was no statistically significant change in wrist range of motion (ROM), however. Arthroscopic debridement of the central perforation (1A lesion) with concomitant repair of the ulnar detachment (1B lesion) resulted in functional and symptomatic improvement. This combined 1A/1B TFC injury is not reliably diagnosed preoperatively and should be considered a new subset in the Palmer classification, as this will raise awareness of its presence and assist in preoperative planning of such lesions. PMID- 27281314 TI - Cardiovascular Disease Prevalence in Patients with Osteoarthritis, Gout, or Both. AB - OBJECTIVE: Osteoarthritis (OA) and gout have each been associated with increased cardiovascular disease (CVD), but their relative impact is unknown. We compared CVD rates among patients with gout versus patients with OA and no gout (OA-only). METHODS: We identified male patients at the VA New York Harbor Healthcare System with gout (with or without concur - rent OA) and with OA-only between August 2007 and August 2008. For each group, we collected baseline demographic data and CVD risk factors. The primary outcome was a composite index (CV4) of any diagnosis of coronary artery disease (CAD), angina, myocardial infarction (MI), or coro- nary bypass surgery (CABG). Secondary outcomes included individual diagnoses within the CV4, CHF, and death. We subsequently divided the gout patients into those who did versus did not have concurrent diagnoses of OA (gout-only; gout+OA). Logistic regression was used to compare the associations of OA-only, gout-only, and gout+OA with CV outcomes. RESULTS: 1,280 gout subjects met inclusion criteria (983 gout- only and 297 gout+OA), along with 1,231 OA-only subjects. Gout subjects overall had more CVD risk factors at baseline, including hypertension, hyperlipidemia, and chronic kidney disease, versus OA-only. Compared with OA only, gout subjects overall had increased rates of all outcomes except MI. Both the gout-only and gout+OA subgroups also had increased risk for all outcomes except MI, and CABG in the case of gout+OA subjects. After adjusting for traditional CVD risk factors, both gout-only and gout+OA subjects continued to have increased risk for multiple CVD outcomes. Gout+OA did not impart ad- ditional risk over gout-only for any outcome studied. CONCLUSION: Our data suggest that gout is associated with higher risk of CVD compared with OA, and that OA does not impart any additive CVD risk to patients who also have gout. Significance and Innovations: * In our dataset, gout subjects both with and without con- comitant OA had more cardiovascular disease (CVD) risk factors at baseline, and higher prevalence of CVD outcomes, than patients with OA only. * After adjusting for traditional CVD risk factors, gout-only and gout+OA subjects continued to have increased rates of multiple CVD outcomes, suggesting an intrinsic CVD risk to the diagnosis of gout, compared with OA. * These observations underline that gout patients represent a group at increased CVD risk, for whom both rheumatic disease management and CVD prevention need to be addressed. PMID- 27281316 TI - Examination Under Anesthesia for Posterior Wall Acetabular Fracture A Survey of the OTA Membership. AB - OBJECTIVES: The purpose of this survey was to learn more about the indications, criteria, and methods surgeons use for performing examination under anesthesia (EUA) for "intermediate" sized posterior wall acetabular fractures (those involving 20% to 40% of the posterior wall) and to find what criteria are used to determine hip instability. METHODS: An 18 question survey was posted on the Ortho paedic Trauma Association's website and was used to gather anonymous data from orthopaedic surgeons regarding their approach to the intermediate sized posterior wall fracture. RESULTS: Considerable variability existed among re- sponses to many of the questions asked. Based on the an - swers given to the survey, a consensus of 75% or more of respondents was found for the following: 1. Supine position for the examination (100%); 2. "Live" fluoroscopy is used during the examination (97%); 3. The AP and obturator oblique are the x-rays most frequently used (81% and 76%, respectively); 4. The hip is placed in flexion and adduction during the exam (100% and 84%, respectively); 5. Axial load is applied during the examination (90%); Finally, 6. instabil - ity is defined as subluxation on exam by most respondents (98%), and any perceived visible subluxation is what defines instability (88%). CONCLUSION: Most surgeons agreed with the following: 1. Supine is the position of choice for the examination; 2. "Live" fluoroscopy is used during the examination; 3. The AP and obturator oblique are the x-rays most frequently used; 4. The hip is placed in flexion and adduction during the exam; 5. Axial load is applied during the examination; and 6. Instability is defined as subluxation on exam. PMID- 27281317 TI - Rotator Cuff Fatty Infiltration Are Coronal Images More Helpful for Characterization than Sagittal Images? AB - OBJECTIVE: To assess for a difference in the characteriza - tion of rotator cuff (RC) muscle fatty infiltration (FI) between the sagittal and coronal planes in the setting of a large or massive RC tear. MATERIALS AND METHODS: Retrospective review of pa - tients with MRIs demonstrating large or massive RC tears (study group-SG) and no tearing (control group-CG) was conducted. Sagittal T1W and coronal PD images of the supraspinatus and infraspinatus muscles from each patient were selected, separated, and placed in random order. Three MSK readers reviewed the images blindly and independently and qualified the FI based on the Goutallier classification. RESULTS: The SG included 15 men and 15 women (mean age: 65; range: 45 to 87 years); CG included 10 men and 10 women (mean age: 60; range 45 to 76 years). Statistically significant (SS) discrepancies in the assessment of the FI between the sagittal and coronal images occurred 62% in SG and 33% in CG, (p < 0.001). In SG, each reader demon - strated a SS tendency (p < 0.04) to assign a higher value to each muscle when grading the sagittal images compared to coronal images. In SG, 33% of the time (37% supraspinatus, 29% infraspinatus), there was a grade greater than or equal to 3 assigned on the sagittal images but less than 3 grade on corresponding coronal images. CONCLUSION: There was a statistically significant differ - ence in the characterization of RC FI between the sagittal and coronal planes in the setting of a large or massive tear, likely related to incomplete visualization of the musculature on sagittal imaging secondary to muscle and tendon retrac - tion and more complete visualization on coronal imaging. Awareness of this difference may allow for a more accurate characterization of the degree of fatty infiltration. PMID- 27281318 TI - Can Flexible Instruments Create Adequate Femoral Tunnel Lengths at 90 degrees of Knee Flexion in Anterior Cruciate Ligament Reconstruction? AB - PURPOSE: This study aims to study femoral tunnel lengths drilled with a flexible reamer and the distance to important lateral structures obtained by flexing the knee at various angles and by drilling the guide pins arthroscopically to resemble clinical practice. The purpose of this cadaveric study was twofold: 1. to determine whether femoral tunnel lengths of greater than 20 mm can be created with a flexible reamer system at 90 degrees of knee flexion and 2. to determine whether the lateral structures of the knee are safe with this technique. METHODS: Ten fresh cadaveric knees were utilized. The intra-osseous length can be measured with a specially de - signed flexible guide pin. Flexible pins were inserted with the knee at 70 degrees , 90 degrees , and 120 degrees of flexion. The intra osseous length was measured with the measuring device. Each speci - men was dissected around the lateral aspect of the knee to identify the critical structures, the common peroneal nerve, and the LCL. The distance from the guide pins to the com - mon peroneal nerve and femoral attachment of the LCL were measured with a standard flexible paper ruler to the nearest millimeter. RESULTS: There is a trend for progressively increasing mean intra-osseous length associated with increased flexion of the knee. The mean intra-osseous length for 70 degrees flexion was 25.2 mm (20 mm to 32 mm), which was statistically significant when compared to mean intra-osseous lengths of 32.1 mm (22 mm to 45 mm) and 38.0 mm (34 mm to 45 mm) in the 90 degrees and 120 degrees flexion groups, respectively (p < 0.05). There were no significant differences among the groups with respect to distance to the LCL. There is a trend toward longer distances to the common peroneal nerve with increased flexion. There was a statistically significant dif - ference when comparing 120 degrees versus 70 degrees (p < 0.05). CONCLUSIONS: This study that shows that adequate femoral tunnel lengths can be safely created without knee hyperflex - ion using flexible instruments via an anteromedial portal. PMID- 27281319 TI - The Effects of Hospital Closure on the Local Utilization of Total Joint Replacement The Queens Experience. AB - Since 2000, 31 hospitals have closed in New York State. This has primarily been due to the financial difficulties endured by these institutions, many of which were located in areas inhabited predominantly by patients of lower socioeconomic status. Additionally, recommendations by the NYS Depart- ment of Health (Berger Commission) cited excess hospital capacity as a driver for the struggles of the healthcare delivery system in New York, forcing financially stable in - stitutions to close their doors as well. Data has shown that outcomes are improved when complex procedures, such as joint arthroplasty, are performed at high volume hospitals. However, for patients in the outer boroughs of NYC, travel to these specialized centers may be too expensive and physi- cally difficult for poor patients with severe osteoarthritis. Using the SPARCS database, we identified a temporary decrease in utilization of lower extremity total joint replace - ment in the areas immediately adjacent to closed hospitals. This does not appear to have a lasting effect as illustrated by quick return back to pre closure trends and further in- crease when compared with regional trends. This effect is more pronounced in urban areas where public transportation and traffic are more of an issue for patients, making it more difficult to travel with the goal of seeking care elsewhere. PMID- 27281320 TI - Ilizarov Method for Bone Lengthening and Defect Management Review of Contemporary Literature. AB - Since its origination in the middle of the past century, the Ilizarov method has advanced greatly and has become a viable method for bone lengthening, severe deformity correc- tion, and defect management. As the reported studies show, it remains one of the most used tools for bone reconstruction. The original method and its modifications continue to be the topic of interest for orthopaedic scientists as evidenced by the number of clinical studies on the Ilizarov method that have been published in orthopaedic journals in the period from 2000 through 2014, most of which present the out- comes of treating large series of patients using distraction osteogenesis for bone lengthening, defect management, and deformity correction. We made a review of contemporary clinical studies on the Ilizarov method used for bone length- ening and defect management. PMID- 27281321 TI - The Etiology of Improved Outcomes at High Volume Centers Learning Theory and the Case of Implant Flashing. AB - Increased volume has been shown to be associated with improved outcomes for many orthopaedic procedures. For individual surgeons, the concepts of learning curves and volume effects have been well established in the literature. For institutions, high-volume hospitals have also been shown to have better outcomes for orthopaedic procedures such as total joint replacements. However, exactly how hospital volume mediates this improvement is not well understood. Learning theory states that learning occurs as a result of accumulated experience, not based on time. We compared our institution's curve representing our implant flashing rates to other institutional data sets that exhibit learning and continuous quality improvement, including airline near misses, coal mining accidents, and others. Development of expertise is based on volume and rate of errors, and therefore higher volume is conducive to faster learning. PMID- 27281322 TI - Surgical Fracture Repair in Chronic Renal Failure Patients on Hemodialysis An Analysis of Complications and Hospital Quality Measures. AB - In end stage renal disease (ESRD) patients on hemodialysis (HD), it is known that renal bone disease has a negative impact on postoperative complication rate of fracture repair compared to non-ESRD patients. Previous studies have examined complications following surgical hip fracture repair in ESRD patients on HD. However, there is paucity of information outside of hip fracture repair. This study was undertaken to investigate complications associated with surgical fracture repair in ESRD patients on hemodialysis and to compare quality measures with a control group for various fracture types. Data of all consecutive ESRD patients on HD was collected prospectively starting in 2013. Charts of 2,558 ESRD patients on HD from 2010 to 2013 were also reviewed. Thirty-four patients who underwent surgical fracture repair were included in the study. Additionally, 1,000 patients without ESRD who underwent fracture repair were also identified, and a random sample of 267 patients was selected for inclusion as a control group. Primary outcomes were major complications as defined by the Clavien-Dindo complication rating system for orthopaedic surgery. Secondary outcomes were minor complications, defined by the same method. Demographic information and hospital quality measures, such as hospital length of stay (LOS) and discharge disposition, were also collected. There were no differences between the two groups in terms of BMI, ethnicity, or gender distribution. The ESRD patients were older than control patients (62.6 versus 46.8 years; p > 0.01). Overall, the complication rate in the ESRD group was 14.7% compared to 3% in the control group (p < 0.05) while the rate of major complications was similar (5.8% versus 2.2%, p = 0.2). The rate of minor complications was higher in the ESRD group though this did not reach statistical significance (8.8% versus 1%, p = 0.07). Median LOS was significantly higher in the ESRD group (15.9 versus 6.4 days; p < 0.01), and patients in the ESRD group were less likely to be discharged to home (29.4% versus 78%; p < 0.01). Surgical fracture repair in ESRD patients can be performed with similar major complication rate as a control group. However, the higher rate of minor complications and poorer hospital quality measures in the ESRD group must be taken into account as we move toward "pay for performance" and bundled payment initiatives for orthopaedic trauma patients. PMID- 27281323 TI - Calcaneonavicular Coalition with Naviculocuneiform and Cuneiform-First Metatarsal Coalitions A Case Report. AB - Coalitions involving three joints of the midfoot are rare. To our knowledge, this is the first report of a patient having fibrocartilaginous coalition of the calcaneonavicular joint along with partial osseous fusion of the naviculocuneiform (Chopart's joint) and medial cuneiform-first metatarsal joints. These multi-coalition pathologies are challenging to address operatively as pain can persist even after recognizing and surgically addressing each coalition in a patient. PMID- 27281324 TI - Indirect Popliteal Artery Transections in Revision Total Knee Arthroplasty A Case Report. AB - Popliteal artery injury in total knee arthroplasty (TKA) is rare but a devastating complication with consequence from transient bleeding to death. We report a case of 83-yearold woman suffering from an unusual early postoperative indirect popliteal artery transection in revision TKA for an infected knee. This injury was triggered by surgical correction of stiffened and distorted soft tissue, which resulted in excessive tensioning and eventual indirect transection of the artery. To avoid this devastating complication, early elimination of infection concomitant with perioperative maintenance of the normal anatomy of the knee is important. PMID- 27281325 TI - The Teenage Terrible Triad A Case Report. AB - Anterior shoulder dislocation in the athlete may result in an assortment of injuries that often benefit from surgical stabilization procedures. These injury patterns can be complex, requiring a multimodal approach to treatment. We present a rare case of a traumatic anterior shoulder dislocation in a teenage athlete that resulted in humeral avulsion of the glenohumeral ligament, rotator cuff tear, and axillary nerve palsy. Surgical treatment enabled return to football within 1 year of injury, and full function was restored. PMID- 27281326 TI - Management of Lower Extremity and Pelvic Tumors Using Computer Assisted Modeling (CAM) A Case Series. AB - Computer assisted modeling (CAM) has become an important tool in surgical oncology and reconstructive surgery. The preservation of the limb is an important consideration when approaching the treatment of lower extremity and pelvic tumors. The use of cutting guides allows for optimal conservation of disease-free bone and maintenance of function. We present a small case series that illustrates the use of CAM in patients with lower extremity and pelvic bone tumors. PMID- 27281328 TI - Honey Bee (Apis mellifera) Queen Reproductive Potential Affects Queen Mandibular Gland Pheromone Composition and Worker Retinue Response. AB - Reproductive division of labor is one of the defining traits of honey bees (Apis mellifera), with non-reproductive tasks being performed by workers while a single queen normally monopolizes reproduction. The decentralized organization of a honey bee colony is maintained in large part by a bouquet of queen-produced pheromones, the distribution of which is facilitated by contact among workers throughout the hive. Previous studies have shown that the developmental fate of honey bee queens is highly plastic, with queens raised from younger worker larvae exhibiting higher measures of reproductive potential compared to queens raised from older worker larvae. We investigated differences in the chemical composition of the mandibular glands and attractiveness to workers of "high-quality" queens (i.e., raised from first instar worker larvae; more queen-like) and "low-quality" queens (i.e., raised from third instar worker larvae; more worker-like). We characterized the chemical profiles of the mandibular glands of high-quality queens and low-quality queens using GC-MS and used the worker retinue response as a measure of the attractiveness to workers of high-quality queens vs. low-quality queens. We found that queen quality affected the chemical profiles of mandibular gland contents differently across years, showing significant differences in the production of the queen mandibular pheromone ("QMP") components HVA and 9-HDA in 2010, but no significant differences of any glandular compound in 2012. We also found that workers were significantly more attracted to high-quality queens than to low-quality queens in 2012, possibly because of increased attractiveness of their mandibular gland chemical profiles. Our results indicate that the age at which honey bee larvae enter the "queen-specific" developmental pathway influences the chemical composition of queen mandibular glands and worker behavior. However, these changes are not consistent across years, suggesting that other external factors may play important roles in modulating queen quality. PMID- 27281330 TI - Essential Oils and Pure Volatile Compounds as Potential Drugs in Alzheimer's Disease Therapy: An Updated Review of the Literature. AB - BACKGROUND: The use of aromatic plants to relief different illness is not a new therapy. Actually aromatic plants have been used for many centuries by different cultures around the world. Pharmacological studies provide scientific support to the traditional use of aromatic medicinal plants and aromatherapy; nevertheless, more clinical trials are required regarding to their effectiveness in order to establish a guidance for their use in routine healthcare. Moreover, modern medicine in studies about olfactory function has attained great achievements and got Nobel Prize in 2004. These new searches have obviously fueled interest in the essential oils and volatile compounds of natural origin. Several reviews on the newly discovered AChEi obtained from plants, fungus and marine organisms have also been published over the last years. The majority of these AChEi belong to the alkaloid group, including indole, isoquinoline, quinolizidine, piperidine and steroidal alkaloids. RESULTS: Probably the interest in the essential oils and volatile compounds will be fueled from the new available scientific data about receptor on olfactory mucosa of nasal cavity. It can receive and distinguish different odor molecules, which produce nerve impulse and transmit into olfactory bulb via olfactory nerves. The nerve cells in the olfactory bulb transmit the signals into hippocampus. Because hippocampus is closely related with learning and memory functions, the volatile compounds can be potential drugs in AD therapies. PMID- 27281329 TI - Antiplatelet Treatment in Peripheral Arterial Disease: The Role of Novel Antiplatelet Agents. AB - BACKGROUND: Acetylsalicylic acid and clopidogrel are two antiplatelet agents currently used in the therapy of peripheral arterial disease. Cilostazol also inhibits platelet aggegration. These agents present limitations that novel antiplatelet agents may overcome. OBJECTIVE: The aim of this manuscript is to review current data on the use of novel antiplatelet agents in peripheral arterial disease. METHOD: An extensive search in the English medical literature has yielded a number of publications on a number of novel antiplatelet agents; atopaxar, vorapaxar, cangrelor, ticagrelor, elinogrel, and prasugrel. RESULTS: Data on atopaxar, vorapaxar, cangrelor, ticagrelor, elinogrel and prasugrel come mainly from cardiology publications. Limitations, side effects and effectiveness of each of these agents are studied, but their use in peripheral arterial disease is limited, especially for those agents that have not still been approved for this indication. As expected, main side effect of most of these agents is haemorrhage, but other important side effects limit the use of some of these agents in specific subgroups of patients. CONCLUSION: Novel antiplatelet agents demonstrate a range of promising characteristics, but further study and clinical trials are necessary for them to be considered safe and effective. PMID- 27281331 TI - Current Perspective in the International Trade of Medicinal Plants Material: An Update. AB - BACKGROUND: The recent years have seen an increased interest in medicinal plants together with the therapeutic use of phytochemicals. Medicinal plants are utilized by the industry for the production of extracts, phytopharmaceuticals, nutraceuticals and cosmeceuticals and their use is expected to grow faster than the conventional drugs. The enormous demand of medicinal plant material has resulted in huge trade both at domestic and international levels. METHODS: The trade data of medicinal plant material with commodity code HS 1211 (SITC.4, code 292.4) and their derived/related products which are traded under different commodity codes has been acquired from COMTRADE, Trade Map, country reports, technical documents etc for the period 2001 to 2014. The data was analyzed using statistical tools to draw conclusions. RESULTS: The significant features of the global trade; the leading source, consumer, import and export countries; and the striking trends are presented. The trade of the ten key countries and the selected important items is also discussed in detail. The conservative figure of trade of medicinal plants materials and their derived/related products including extracts, essential oils, phytopharmaceuticals, gums, spices used in medicine, tannins for pharmaceutical use, ingredients for cosmetics etc. as calculated from the global export data for the year 2014 is estimated at USD 33 billion. The average global export in medicinal plants under HS 1211 for the fourteen year period was USD 1.92 billion for 601,357 tons per annum and for the year 2014 it stood at 702,813 tons valued at USD 3.60 billion. CONCLUSION: For the studied period, an annual average growth rate (AAGR) of 2.4% in volumes and 9.2% in values of export was observed. Nearly 30% of the global trade is made up by top two countries of the import and export. China and India from Asia; Egypt and Morocco from Africa; Poland, Bulgaria and Albania from Europe; Chile and Peru from South America are important supply sources. The USA, Japan and Europe are the major consumers of the world. PMID- 27281327 TI - Targeted and Untargeted Approaches Unravel Novel Candidate Genes and Diagnostic SNPs for Quantitative Resistance of the Potato (Solanum tuberosum L.) to Phytophthora infestans Causing the Late Blight Disease. AB - The oomycete Phytophthora infestans causes late blight of potato, which can completely destroy the crop. Therefore, for the past 160 years, late blight has been the most important potato disease worldwide. The identification of cultivars with high and durable field resistance to P. infestans is an objective of most potato breeding programs. This type of resistance is polygenic and therefore quantitative. Its evaluation requires multi-year and location trials. Furthermore, quantitative resistance to late blight correlates with late plant maturity, a negative agricultural trait. Knowledge of the molecular genetic basis of quantitative resistance to late blight not compromised by late maturity is very limited. It is however essential for developing diagnostic DNA markers that facilitate the efficient combination of superior resistance alleles in improved cultivars. We used association genetics in a population of 184 tetraploid potato cultivars in order to identify single nucleotide polymorphisms (SNPs) that are associated with maturity corrected resistance (MCR) to late blight. The population was genotyped for almost 9000 SNPs from three different sources. The first source was candidate genes specifically selected for their function in the jasmonate pathway. The second source was novel candidate genes selected based on comparative transcript profiling (RNA-Seq) of groups of genotypes with contrasting levels of quantitative resistance to P. infestans. The third source was the first generation 8.3k SolCAP SNP genotyping array available in potato for genome wide association studies (GWAS). Twenty seven SNPs from all three sources showed robust association with MCR. Some of those were located in genes that are strong candidates for directly controlling quantitative resistance, based on functional annotation. Most important were: a lipoxygenase (jasmonate pathway), a 3-hydroxy-3-methylglutaryl coenzyme A reductase (mevalonate pathway), a P450 protein (terpene biosynthesis), a transcription factor and a homolog of a major gene for resistance to P. infestans from the wild potato species Solanum venturii. The candidate gene approach and GWAS complemented each other as they identified different genes. The results of this study provide new insight in the molecular genetic basis of quantitative resistance in potato and a toolbox of diagnostic SNP markers for breeding applications. PMID- 27281332 TI - Phytochemicals: Potential in Management of Climacteric Neurobiology. AB - Menopause jeopardizes the integrity of brain and makes it vulnerable to various diseases, both of psychiatric and degenerative nature. Exogenous estrogen supplementation confers neuroprotection but the results of Women's Health Initiative (WHI), Million Women Study (MWS) and incidence of endometrial cancer, breast cancer and venous thromboembolism reported with estrogen use have engendered doubts over its clinical translation for postmenopausal neurological disorders. Scientific community and general public have started recognizing the protective potential of phytochemicals in climacteric medicine. These phytochemicals are plant-derived, non-steroidal bioactive estrogenic compounds. Emerging preclinical studies have suggested that these phytochemicals display potential benefits in mitigating postmenopausal depression, anxiety, cerebral ischemia and cognitive dysfunction. Thus, the aim of present review is: a) to give an overview of neuroprotective action of estrogen, b) to address the chemical and pharmacological features of various classes of phytoestrogens, and c) to present preclinical and clinical evidence of effect of phytoestrogens on climacteric neurobiology with their possible mechanisms of action. PMID- 27281333 TI - Challenges in the Development of Antifungal Agents Against Candida: Scope of Phytochemical Research. AB - BACKGROUND: Infections caused by Candida have become a major source of morbidity and mortality. Limited numbers of drugs are available to treat these infections. Phytochemicals can be the major source of antifungal compounds. The aim of this publication was to review the current literature to assess the challenges and scope of phytochemical research in the development of new antifungal drugs. METHODS: Literature describing cellular nature of Candida, the development of drug resistance and target sites for the new drugs were assessed. Publications reporting antifungal activities of crude extracts of plants, their essential oils and identified chemical constituents were also summarised. RESULTS: The results showed that the development of new antifungal agents from natural sources is a complex process due to the cellular nature of Candida and the types of infections caused, such as superficial to life threatening systemic mycosis which necessitate systemic and topical use of drugs. Efficacy of the drugs in the presence of body fluids, normal flora and medical devices can also pose a challenge. Synthetic, semi-synthetic and natural compounds can be screened for their antifungal activities against emerging target sites using new cost effective techniques to increase throughput. Their efficacy, substantivity and site specific desired drug delivery can be enhanced using nanotechnology, hydrogel formulation and bio-adhesive technology. Finally, partnership between academic research laboratories and pharmaceutical industries is also necessary. CONCLUSION: Many challenges are identified in the development of new antifungal drugs, however phytochemicals are still the major source of new antifungal drugs and should be strategically explored. PMID- 27281334 TI - The Role of Platelets in Cardiovascular Disease: Molecular Mechanisms. AB - The role of platelets in atherosclerotic process and subsequently in the pathophysiology of cardiovascular disease is essential as platelets in addition to their contribution to thrombosis and hemostasis modulating inflammatory reactions and immune response. Platelets after adhesion on the injured vascular endothelium and activation release a wide range of molecules stored in platelets granules such as chemokines, proinflammatory molecules and other biological response modulators accelerating interaction among platelets, endothelial cells and leukocytes. These interactions establish a localized inflammatory response that promotes the atherosclerotic process. Moreover, activated platelets give rise to microparticles another active participant within the blood stream. The purpose of this review is to present the role of platelets in the above mechanisms giving an emphasis on the nature of the platelet derived- molecules and their contribution to the atherosclerotic process. PMID- 27281336 TI - Bayesian Solutions for Handling Uncertainty in Survival Extrapolation. AB - OBJECTIVE: Survival extrapolation using a single, best-fit model ignores 2 sources of model uncertainty: uncertainty in the true underlying distribution and uncertainty about the stability of the model parameters over time. Bayesian model averaging (BMA) has been used to account for the former, but it can also account for the latter. We investigated BMA using a published comparison of the Charnley and Spectron hip prostheses using the original 8-year follow-up registry data. METHODS: A wide variety of alternative distributions were fitted. Two additional distributions were used to address uncertainty about parameter stability: optimistic and skeptical. The optimistic (skeptical) model represented the model distribution with the highest (lowest) estimated probabilities of survival but reestimated using, as prior information, the most optimistic (skeptical) parameter estimated for intermediate follow-up periods. Distributions were then averaged assuming the same posterior probabilities for the optimistic, skeptical, and noninformative models. Cost-effectiveness was compared using both the original 8-year and extended 16-year follow-up data. RESULTS: We found that all models obtained similar revision-free years during the observed period. In contrast, there was variability over the decision time horizon. Over the observed period, we detected considerable uncertainty in the shape parameter for Spectron. After BMA, Spectron was cost-effective at a threshold of L20,000 with 93% probability, whereas the best-fit model was 100%; by contrast, with a 16-year follow-up, it was 0%. CONCLUSIONS: This case study casts doubt on the ability of the single best-fit model selected by information criteria statistics to adequately capture model uncertainty. Under this scenario, BMA weighted by posterior probabilities better addressed model uncertainty. However, there is still value in regularly updating health economic models, even where decision uncertainty is low. PMID- 27281335 TI - Tie2 Expressing Monocytes in the Spleen of Patients with Primary Myelofibrosis. AB - Primary myelofibrosis (PMF) is a Philadelphia-negative (Ph-) myeloproliferative disorder, showing abnormal CD34+ progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2) have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs), and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14+ cells are Tie2+ and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2+CD14lowCD16brightCDL62-CCR2- (TEMs) and their frequency was higher (p = 0.008) in spleen tissue-derived mononuclear cells (MNCs) of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14+ cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14+Tie2+ cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2+ monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ. PMID- 27281337 TI - Cost-effectiveness Analysis in R Using a Multi-state Modeling Survival Analysis Framework: A Tutorial. AB - This tutorial provides a step-by-step guide to performing cost-effectiveness analysis using a multi-state modeling approach. Alongside the tutorial, we provide easy-to-use functions in the statistics package R. We argue that this multi-state modeling approach using a package such as R has advantages over approaches where models are built in a spreadsheet package. In particular, using a syntax-based approach means there is a written record of what was done and the calculations are transparent. Reproducing the analysis is straightforward as the syntax just needs to be run again. The approach can be thought of as an alternative way to build a Markov decision-analytic model, which also has the option to use a state-arrival extended approach. In the state-arrival extended multi-state model, a covariate that represents patients' history is included, allowing the Markov property to be tested. We illustrate the building of multi state survival models, making predictions from the models and assessing fits. We then proceed to perform a cost-effectiveness analysis, including deterministic and probabilistic sensitivity analyses. Finally, we show how to create 2 common methods of visualizing the results-namely, cost-effectiveness planes and cost effectiveness acceptability curves. The analysis is implemented entirely within R. It is based on adaptions to functions in the existing R package mstate to accommodate parametric multi-state modeling that facilitates extrapolation of survival curves. PMID- 27281338 TI - Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment. AB - Receptor-targeted lentiviral vectors (LVs) can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV) glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 A distance). Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV) glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4) was substantially enhanced by reducing receptor size to below 100 A. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs. PMID- 27281339 TI - Microarray Noninvasive Neuronal Seizure Recordings from Intact Larval Zebrafish. AB - Zebrafish epilepsy models are emerging tools in experimental epilepsy. Zebrafish larvae, in particular, are advantageous because they can be easily genetically altered and used for developmental and drug studies since agents applied to the bath penetrate the organism easily. Methods for electrophysiological recordings in zebrafish are new and evolving. We present a novel multi-electrode array method to non-invasively record electrical activity from up to 61 locations of an intact larval zebrafish head. This method enables transcranial noninvasive recording of extracellular field potentials (which include multi-unit activity and EEG) to identify epileptic seizures. To record from the brains of zebrafish larvae, the dorsum of the head of an intact larva was secured onto a multi electrode array. We recorded from individual electrodes for at least three hours and quantified neuronal firing frequency, spike patterns (continuous or bursting), and synchrony of neuronal firing. Following 15 mM potassium chloride- or pentylenetetrazole-infusion into the bath, spike and burst rate increased significantly. Additionally, synchrony of neuronal firing across channels, a hallmark of epileptic seizures, also increased. Notably, the fish survived the experiment. This non-invasive method complements present invasive zebrafish neurophysiological techniques: it affords the advantages of high spatial and temporal resolution, a capacity to measure multiregional activity and neuronal synchrony in seizures, and fish survival for future experiments, such as studies of epileptogenesis and development. PMID- 27281340 TI - Bayesian Multi-Trait Analysis Reveals a Useful Tool to Increase Oil Concentration and to Decrease Toxicity in Jatropha curcas L. AB - The biggest challenge for jatropha breeding is to identify superior genotypes that present high seed yield and seed oil content with reduced toxicity levels. Therefore, the objective of this study was to estimate genetic parameters for three important traits (weight of 100 seed, oil seed content, and phorbol ester concentration), and to select superior genotypes to be used as progenitors in jatropha breeding. Additionally, the genotypic values and the genetic parameters estimated under the Bayesian multi-trait approach were used to evaluate different selection indices scenarios of 179 half-sib families. Three different scenarios and economic weights were considered. It was possible to simultaneously reduce toxicity and increase seed oil content and weight of 100 seed by using index selection based on genotypic value estimated by the Bayesian multi-trait approach. Indeed, we identified two families that present these characteristics by evaluating genetic diversity using the Ward clustering method, which suggested nine homogenous clusters. Future researches must integrate the Bayesian multi trait methods with realized relationship matrix, aiming to build accurate selection indices models. PMID- 27281341 TI - Role of Gaze Cues in Interpersonal Motor Coordination: Towards Higher Affiliation in Human-Robot Interaction. AB - BACKGROUND: The ability to follow one another's gaze plays an important role in our social cognition; especially when we synchronously perform tasks together. We investigate how gaze cues can improve performance in a simple coordination task (i.e., the mirror game), whereby two players mirror each other's hand motions. In this game, each player is either a leader or follower. To study the effect of gaze in a systematic manner, the leader's role is played by a robotic avatar. We contrast two conditions, in which the avatar provides or not explicit gaze cues that indicate the next location of its hand. Specifically, we investigated (a) whether participants are able to exploit these gaze cues to improve their coordination, (b) how gaze cues affect action prediction and temporal coordination, and (c) whether introducing active gaze behavior for avatars makes them more realistic and human-like (from the user point of view). METHODOLOGY/PRINCIPAL FINDINGS: 43 subjects participated in 8 trials of the mirror game. Each subject performed the game in the two conditions (with and without gaze cues). In this within-subject study, the order of the conditions was randomized across participants, and subjective assessment of the avatar's realism was assessed by administering a post-hoc questionnaire. When gaze cues were provided, a quantitative assessment of synchrony between participants and the avatar revealed a significant improvement in subject reaction-time (RT). This confirms our hypothesis that gaze cues improve the follower's ability to predict the avatar's action. An analysis of the pattern of frequency across the two players' hand movements reveals that the gaze cues improve the overall temporal coordination across the two players. Finally, analysis of the subjective evaluations from the questionnaires reveals that, in the presence of gaze cues, participants found it not only more human-like/realistic, but also easier to interact with the avatar. CONCLUSION/SIGNIFICANCE: This work confirms that people can exploit gaze cues to predict another person's movements and to better coordinate their motions with their partners, even when the partner is a computer animated avatar. Moreover, this study contributes further evidence that implementing biological features, here task-relevant gaze cues, enable the humanoid robotic avatar to appear more human-like, and thus increase the user's sense of affiliation. PMID- 27281342 TI - CDK-1 Inhibition in G2 Stabilizes Kinetochore-Microtubules in the following Mitosis. AB - Cell proliferation is driven by cyclical activation of cyclin-dependent kinases (CDKs), which produce distinct biochemical cell cycle phases. Mitosis (M phase) is orchestrated by CDK-1, complexed with mitotic cyclins. During M phase, chromosomes are segregated by a bipolar array of microtubules called the mitotic spindle. The essential bipolarity of the mitotic spindle is established by the kinesin-5 Eg5, but factors influencing the maintenance of spindle bipolarity are not fully understood. Here, we describe an unexpected link between inhibiting CDK 1 before mitosis and bipolar spindle maintenance. Spindles in human RPE-1 cells normally collapse to monopolar structures when Eg5 is inhibited at metaphase. However, we found that inhibition of CDK-1 in the G2 phase of the cell cycle improved the ability of RPE-1 cells to maintain spindle bipolarity without Eg5 activity in the mitosis immediately after release from CDK-1 inhibition. This improved bipolarity maintenance correlated with an increase in the stability of kinetochore-microtubules, the subset of microtubules that link chromosomes to the spindle. The improvement in bipolarity maintenance after CDK-1 inhibition in G2 required both the kinesin-12 Kif15 and increased stability of kinetochore microtubules. Consistent with increased kinetochore-microtubule stability, we find that inhibition of CDK-1 in G2 impairs mitotic fidelity by increasing the incidence of lagging chromosomes in anaphase. These results suggest that inhibition of CDK-1 in G2 causes unpredicted effects in mitosis, even after CDK-1 inhibition is relieved. PMID- 27281343 TI - Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N Linked Glycosylation: Effect of Glucose Condition. AB - ATP-binding cassette C11 (ABCC11) is a plasma membrane protein involved in the transport of a variety of lipophilic anions. ABCC11 wild-type is responsible for the high-secretion phenotypes in human apocrine glands, such as that of wet-type ear wax, and the risk of axillary osmidrosis. We have previously reported that mature ABCC11 is a glycoprotein containing two N-linked glycans at Asn838 and Asn844. However, little is known about the role of N-linked glycosylation in the regulation of ABCC11 protein. In the current study, we investigated the effects of N-linked glycosylation on the protein level and localization of ABCC11 using polarized Madin-Darby canine kidney II cells. When the N-linked glycosylation in ABCC11-expressing cells was chemically inhibited by tunicamycin treatment, the maturation of ABCC11 was suppressed and its protein level was significantly decreased. Immunoblotting analyses demonstrated that the protein level of the N linked glycosylation-deficient mutant (N838Q and N844Q: Q838/844) was about half of the ABCC11 wild-type level. Further biochemical studies with the Q838/844 mutant showed that this glycosylation-deficient ABCC11 was degraded faster than wild-type probably due to the enhancement of the MG132-sensitive protein degradation pathway. Moreover, the incubation of ABCC11 wild-type-expressing cells in a low-glucose condition decreased mature, glycosylated ABCC11, compared with the high-glucose condition. On the other hand, the protein level of the Q838/844 mutant was not affected by glucose condition. These results suggest that N-linked glycosylation is important for the protein stability of ABCC11, and physiological alteration in glucose may affect the ABCC11 protein level and ABCC11-related phenotypes in humans, such as axillary osmidrosis. PMID- 27281344 TI - Investigation of NS3 Protease Resistance-Associated Variants and Phenotypes for the Prediction of Treatment Response to HCV Triple Therapy. AB - Triple therapy of chronic hepatitis C virus (HCV) infection with boceprevir (BOC) or telaprevir (TVR) leads to virologic failure in many patients which is often associated with the selection of resistance-associated variants (RAVs). These resistance profiles are of importance for the selection of potential rescue treatment options. In this study, we sequenced baseline NS3 RAVs population-based and investigated the sensitivity of NS3 phenotypes in an HCV replicon assay together with clinical factors for a prediction of treatment response in a cohort of 165 German and Swiss patients treated with a BOC or TVR-based triple therapy. Overall, the prevalence of baseline RAVs was low, although the frequency of RAVs was higher in patients with virologic failure compared to those who achieved a sustained virologic response (SVR) (7% versus 1%, P = 0.06). The occurrence of RAVs was associated with a resistant NS3 quasispecies phenotype (P<0.001), but the sensitivity of phenotypes was not associated with treatment outcome (P = 0.2). The majority of single viral and host predictors of SVR was only weakly associated with treatment response. In multivariate analyses, low AST levels, female sex and an IFNL4 CC genotype were independently associated with SVR. However, a combined analysis of negative predictors revealed a significantly lower overall number of negative predictors in patients with SVR in comparison to individuals with virologic failure (P<0.0001) and the presence of 2 or less negative predictors was indicative for SVR. These results demonstrate that most single baseline viral and host parameters have a weak influence on the response to triple therapy, whereas the overall number of negative predictors has a high predictive value for SVR. PMID- 27281346 TI - The feeding-nutrition connection, three aspects for its understanding. AB - Feeding is not an isolated concept; it is linked to biological, psychological, cultural, political and economic determinants. Physiologically the meeting of the biological need is very important, but when a group is subjected to a diet that only satisfies hunger and does not provide for nutrients, chronic deficient nutritional stages appear that impact social welfare and health. In this paper, we present three instances of nutritional problems that affect the Mexican population: child malnourishment, obesity and food security. This article exposes some of its social determinants and public policies that address them considering the collective health and its sociology, in the context of social inequality. We highlight the need for public policies that consider social inclusion, for the collective food security, and not merely the pursuit of satisfying hunger, but also to have an accessible, nutritious, and varied diet to prevent alterations in the health of the people. PMID- 27281345 TI - Depression 12-months after coronary artery bypass graft is predicted by cortisol slope over the day. AB - Alterations in the diurnal profile of cortisol have been associated with depressed mood in patients with coronary heart disease. The relationship between cortisol output and depressed mood has not been investigated prospectively in coronary artery bypass graft (CABG) patients before. We aimed to study the relationship between cortisol measured pre- and post-operatively and depression symptoms measured 12 months after CABG surgery. We analysed data from 171 patients awaiting first-time, elective CABG surgery from the pre-assessment clinic at St. George's Hospital, London. The Beck Depression Inventory (BDI) was used to assess depression symptoms and saliva samples were collected to measure diurnal cortisol. Baseline assessments of depression and cortisol were obtained an average 29days before surgery, short-term follow-up of cortisol occurred 60days after surgery and long-term follow-up of depression was assessed 378days after surgery. Baseline cortisol slope was not associated with depression at 12 month follow-up. However, a steeper cortisol slope measured 60days after surgery predicted reduced odds of depression (BDI>=10) 12 months after surgery (odds ratio 0.661, 95% confidence interval 0.437-0.998, p=0.049) after controlling for covariates. These findings suggest interventions aimed at improving adaptation in the early recovery period may have long-term benefits in this patient group. PMID- 27281347 TI - Fabrication of Electrochemical Model Influenza A Virus Biosensor Based on the Measurements of Neuroaminidase Enzyme Activity. AB - Neuroaminidase (NA) enzyme is a kind of glycoprotein that is found on the influenza A virus. During infection, NA is important for the release of influenza virions from the host cell surface together with viral aggregates. It may also be involved in targeting the virus to respiratory epithelial cells. In this study, a model electrochemical influenza A viral biosensor in which receptor-binding properties have been based on NA was developed for the first time. The biosensor's working principle is based on monitoring the interactions between fetuin A and NA enzyme. The assay was monitored step by step by using electrochemical impedance spectroscopy. PMID- 27281348 TI - Do infants have the horizontal bias? AB - A robust set of studies show that adults make more horizontal than vertical and oblique saccades, while scanning real-world scenes. In this paper we study the horizontal bias in infants. The directions of eye movements were calculated for 41 infants (M=8.40 months, SD=3.74, range=3.48-15.47) and 47 adults (M=21.74 years, SD=4.54, range=17.89-39.84) while viewing 28 real-world scenes. Saccade directions were binned to study the proportion of saccades in the horizontal, vertical and oblique directions. In addition, saccade directions were also modeled using a mixture of Von Mises distributions, to account for the relatively large amount of variance in infants data. Horizontal bias was replicated in adults and also found in infants, using both the binning and Von Mises approach. Moreover, a developmental pattern was observed in which older infants are more precise in targeting their saccades than younger infants. That infants have a horizontal bias is important in understanding infants' eye movements. Future studies should account for the horizontal bias in their designs and analyses. PMID- 27281349 TI - Antiinflammatory Effects of Budesonide in Human Fetal Lung. AB - Lung inflammation in premature infants contributes to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without the apparent adverse effects that occur with systemic dexamethasone therapy. Our objective was to determine budesonide potency, stability, and antiinflammatory effects in human fetal lung. We cultured explants of second trimester fetal lung with budesonide or dexamethasone and used microscopy, immunoassays, RNA sequencing, liquid chromatography/tandem mass spectrometry, and pulsating bubble surfactometry. Budesonide suppressed secreted chemokines IL-8 and CCL2 (MCP-1) within 4 hours, reaching a 90% decrease at 12 hours, which was fully reversed 72 hours after removal of the steroid. Half-maximal effects occurred at 0.04-0.05 nM, representing a fivefold greater potency than for dexamethasone. Budesonide significantly induced 3.6% and repressed 2.8% of 14,500 sequenced mRNAs by 1.6- to 95-fold, including 119 genes that contribute to the glucocorticoid inflammatory transcriptome; some are known targets of nuclear factor-kappaB. By global proteomics, 22 secreted inflammatory proteins were hormonally regulated. Two glucocorticoid-regulated genes of interest because of their association with lung disease are CHI3L1 and IL1RL1. Budesonide retained activity in the presence of surfactant and did not alter its surface properties. There was some formation of palmitate-budesonide in lung tissue but no detectable metabolism to inactive 16alpha-hydroxy prednisolone. We concluded that budesonide is a potent and stable antiinflammatory glucocorticoid in human fetal lung in vitro, supporting a beneficial antiinflammatory response to lung-targeted budesonide:surfactant treatment of infants for the prevention of BPD. PMID- 27281350 TI - Revising probability estimates: Why increasing likelihood means increasing impact. AB - Forecasted probabilities rarely stay the same for long. Instead, they are subject to constant revision-moving upward or downward, uncertain events become more or less likely. Yet little is known about how people interpret probability estimates beyond static snapshots, like a 30% chance of rain. Here, we consider the cognitive, affective, and behavioral consequences of revisions to probability forecasts. Stemming from a lay belief that revisions signal the emergence of a trend, we find in 10 studies (comprising uncertain events such as weather, climate change, sex, sports, and wine) that upward changes to event-probability (e.g., increasing from 20% to 30%) cause events to feel less remote than downward changes (e.g., decreasing from 40% to 30%), and subsequently change people's behavior regarding those events despite the revised event-probabilities being the same. Our research sheds light on how revising the probabilities for future events changes how people manage those uncertain events. (PsycINFO Database Record PMID- 27281352 TI - Straight until proven gay: A systematic bias toward straight categorizations in sexual orientation judgments. AB - Perceivers achieve above chance accuracy judging others' sexual orientations, but they also exhibit a notable response bias by categorizing most targets as straight rather than gay. Although a straight categorization bias is evident in many published reports, it has never been the focus of systematic inquiry. The current studies therefore document this bias and test the mechanisms that produce it. Studies 1-3 revealed the straight categorization bias cannot be explained entirely by perceivers' attempts to match categorizations to the number of gay targets in a stimulus set. Although perceivers were somewhat sensitive to base rate information, their tendency to categorize targets as straight persisted when they believed each target had a 50% chance of being gay (Study 1), received explicit information about the base rate of gay targets in a stimulus set (Study 2), and encountered stimulus sets with varying base rates of gay targets (Study 3). The remaining studies tested an alternate mechanism for the bias based upon perceivers' use of gender heuristics when judging sexual orientation. Specifically, Study 4 revealed the range of gendered cues compelling gay judgments is smaller than the range of gendered cues compelling straight judgments despite participants' acknowledgment of equal base rates for gay and straight targets. Study 5 highlighted perceptual experience as a cause of this imbalance: Exposing perceivers to hyper-gendered faces (e.g., masculine men) expanded the range of gendered cues compelling gay categorizations. Study 6 linked this observation to our initial studies by demonstrating that visual exposure to hyper-gendered faces reduced the magnitude of the straight categorization bias. Collectively, these studies provide systematic evidence of a response bias in sexual orientation categorization and offer new insights into the mechanisms that produce it. (PsycINFO Database Record PMID- 27281351 TI - Dispositional contempt: A first look at the contemptuous person. AB - Contempt is a powerful emotion. Marriages fail (Gottman, 1994), coworkers are shamed (Melwani & Barsade, 2011), terrorism is tended toward (Tausch et al., 2011). Despite its importance, contempt has not been investigated at the level of personality. The present research examines how our contemptuous reactions can be conceptualized and measured as a stable individual-difference variable with a range of theoretically predicted correlates. First, we introduce a measure of dispositional contempt, the tendency to look down on, distance, and derogate others who violate our standards. We then unpack the dynamics of dispositional contempt. Across 6 studies using self-report and emotion elicitation in student and MTurk samples (Ns = 165 to 1,368), we examined its (a) nomological network, (b) personality and behavioral correlates, and (c) implications for relationship functioning. Dispositional contempt was distinguished from tendencies toward related emotions and was most associated with dispositional envy, anger, and hubristic pride. Somewhat paradoxically, dispositional contempt was related to being cold and "superior," with associations found with narcissism, other oriented perfectionism, and various antisocial tendencies (e.g., Disagreeableness, Machiavellianism, racism), but it was also related to being self-deprecating and emotionally fragile, with associations found with low self esteem, insecure attachment, and feeling that others impose perfectionistic standards on oneself. Dispositional contempt predicted contemptuous reactions to eliciting film clips, particularly when targets showed low competence/power. Finally, perceiving one's romantic partner as dispositionally contemptuous was associated with lower commitment and satisfaction. Taken together, results give a first look at the contemptuous person and provide a new organizing framework for understanding contempt. (PsycINFO Database Record PMID- 27281353 TI - "Whether I like it or not, it's important": Implicit importance of means predicts self-regulatory persistence and success. AB - To effectively self-regulate, people must persevere on tasks that they deem important, regardless of whether those tasks are enjoyable. Building on past work that has noted the fundamental role of implicit cognition in guiding effective self-regulation, the present paper tests whether an implicit association between goal means and importance predicts self-regulatory persistence and success. Implicit importance predicted markers of effective self-regulation-better grades, more studying and exercise, and stronger standardized testing performance-over and above, and often better than, explicit beliefs about the importance of that self-regulation, as well as implicit evaluations of those means. In particular, those for whom tasks were fairly taxing to complete (i.e., those for whom this self-regulation required effortful self-control) were those who most benefitted from the implicit association between means and importance. Moreover, when participants were reminded of recent self-regulatory failure that they believed could be overcome through hard work, implicit importance toward the means increased as if to prepare them to achieve self-regulatory persistence. A final study sought to reconcile the present findings with previous work showing the key role that implicit evaluations play in effective self-regulation. We reasoned that means are important precisely because they are associated with valued end states. Consistent with this account, implicit evaluations of end-states predicted the implicit importance of means, which in turn predicted effective self-regulation. (PsycINFO Database Record PMID- 27281354 TI - Power and the pursuit of a partner's goals. AB - We investigated how power dynamics in close relationships influence the tendency to devote resources to the pursuit of goals valued by relationship partners, hypothesizing that low (vs. high) power in relationships would lead individuals to center their individual goal pursuit around the goals of their partners. We study 2 related phenomena: partner goal prioritization, whereby individuals pursue goals on behalf of their partners, and partner goal contagion, whereby individuals identify and adopt as their own the goals that their partner pursues. We tested our ideas in 5 studies that employed diverse research methods, including lab experiments and dyadic studies of romantic partners, and multiple types of dependent measures, including experience sampling reports, self-reported goal commitment, and behavioral goal pursuit in a variety of goal domains. Despite this methodological diversity, the studies provided clear and consistent evidence that individuals with low power in their relationships are especially likely to engage in both partner goal prioritization and partner goal contagion. (PsycINFO Database Record PMID- 27281355 TI - "Affective contingencies in the affiliative domain: Physiological assessment, associations with the affiliation motive, and prediction of behavior": Correction to Dufner et al. (2015). AB - Reports an error in "Affective contingencies in the affiliative domain: Physiological assessment, associations with the affiliation motive, and prediction of behavior" by Michael Dufner, Ruben C. Arslan, Birk Hagemeyer, Felix D. Schonbrodt and Jaap J. A. Denissen (Journal of Personality and Social Psychology, 2015[Oct], Vol 109[4], 662-676). In this article an erroneous statement was made regarding the high cutoff filter for the EMG raw signal. The high cutoff filter reported in Appendix B in the Technical Details of the EMG Recording Procedure section should be 300 Hz. (The following abstract of the original article appeared in record 2015-37761-001.) According to classical motive disposition theory, individuals differ in their propensity to derive pleasure from affiliative experiences. This propensity is considered a core process underlying the affiliation motive and a pervasive cause of motivated behavior. In this study, we tested these assumptions. We presented participants with positive affiliative stimuli and used electromyography to record changes in facial muscular activity that are indicative of subtle smiling. We were thus able to physiologically measure positive affect following affiliative cues. Individual differences in these affective contingencies were internally consistent and temporally stable. They converged with affiliation motive self- and informant reports and picture story exercise scores, indicating that they are partly accessible to the self, observable to outsiders, and overlap with implicit systems. Finally, they predicted affiliative behavior in terms of situation selection and modification across a wide variety of contexts (i.e., in daily life, the laboratory, and an online social network). These findings corroborate the long-held assumption that affective contingencies represent a motivational core aspect of affiliation. (PsycINFO Database Record PMID- 27281356 TI - Thank goodness it's Friday: weekly pattern of workplace incivility. AB - BACKGROUND AND OBJECTIVES: Recent research has shown day-level differences in an individual's experience of uncivil behavior; however, it is unknown if that experience follows a consistent weekly change pattern. This study extends incivility theory and research by applying latent growth curve (LGC) modeling to diary study data to understand day-to-day changes in incivility. DESIGN: The authors took a theory-driven approach, reviewing both mood and recovery theory that would support a decrease in incivility over the working week. METHODS: Diary survey methodology was used, with a morning and evening survey completed on five consecutive workdays by 171 (73% of the 235 who initially volunteered, 95% of those who completed any surveys) employees in the legal industry. LGC analysis was used to identify patterns of experienced incivility, mood (both measured after work), and recovery (assessed the following morning). RESULTS: Regardless of job demands and gender, a weekly pattern was identified with the likelihood of experiencing incivility (coded as 0 = none, 1 = some) decreasing from Monday to Friday by .78 each day (p < .001) in a relatively linear fashion with a slope factor of .34 (SE = 0.23; p > .05), indicating invariance between individuals. This weekly pattern was not explained by changes in mood or recovery. CONCLUSIONS: Results emphasize the impact of contextual factors such as time on workplace incivility and the need to consider weekly rhythms of other behaviors that are likely to affect employee well-being and productivity. Although limited to one week of data per person, the findings are likely to be relevant to studies of other forms of interpersonal mistreatment, such as social undermining and interpersonal conflict. PMID- 27281357 TI - Appropriate margin thresholds for isocontour metabolic volumetry of fluorine-18 fluorodeoxyglucose PET in sarcoma: a hybrid PET/MRI study. AB - OBJECTIVES: Metabolic volumetry and heterogeneity indexes are increasingly being used in fluorine-18 fluorodeoxyglucose (F-FDG) PET, mostly using isocontour methods. However, there is no standard method to determine optimal margin thresholds for isocontour volume of interest (VOIiso). Here, VOIiso with various margin thresholds were compared with exact anatomical tumor volumes in sarcoma using a hybrid PET/MRI scanner. PATIENTS AND METHODS: F-FDG PET/MRI images were retrospectively analyzed for 36 lesions of soft tissue or bone sarcoma. VOIiso of tumors was drawn with varying margin thresholds; standardized uptake value (SUV) 1.0-4.0 with an increment of 0.5 and 30-70% of maximal SUV (SUVmax) with an increment of 10%. Exact anatomical tumor volumes (VOIMRI) were drawn manually on the basis of MRI. In each VOI, metabolic tumor volume, SUVmean, total lesion glycolysis, and SD were measured and compared between VOIiso and VOIMRI. RESULTS: Significant correlations were observed between the indexes from VOIiso and VOIMRI. For metabolic tumor volume, no significant difference existed between VOIiso and VOIMRI with margin thresholds of 30 and 40% of SUVmax, and SUV 1.5. For SUVmean, no significant difference existed with 30% of SUVmax, and SUV 1.5. For total lesion glycolysis, no significant difference existed with 40% of SUVmax, SUV 1.5, and 2.0. For SD, no significant difference existed with 30% of SUVmax, SUV 1.5, and 2.0. CONCLUSION: Margin thresholds of 30 or 40% of SUVmax and SUV 1.5 or 2.0 may be used for the VOIiso method in F-FDG PET images of sarcoma. VOIiso with these margin thresholds are expected to produce reliable metabolic, volumetric, and heterogeneity indexes on F-FDG PET images. PMID- 27281358 TI - High metabolic characteristics of uterine fibroids in 18F-FDG PET/CT imaging and the underlying mechanisms. AB - OBJECTIVE: To investigate the high metabolic characteristics of uterine fibroids in fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomographic imaging and the underlying mechanisms. MATERIALS AND METHODS: A total of 47 patients with uterine fibroids who underwent PET/computed tomographic imaging and ultrasound examination from November 2011 to May 2015 were retrospectively analyzed. The characteristics of F-FDG uptake by uterine fibroids were analyzed and their correlations with age, menopause, menstrual cycle, hormone indexes, tumor markers as well as the number and maximum diameter of fibroids in ultrasound images were explored using univariate analysis and multivariate logistic regression analysis. RESULTS: (a) The total positive F-FDG uptake rate and maximum standardized uptake value (SUVmax) were 40.4% (19/47) and 4.38+/-2.57 (1.74-10.81), respectively, in patients with uterine fibroids; (b) univariate analysis showed that age, menopause, estrogen, follicle-stimulating hormone, luteinizing hormone as well as the number of fibroids were correlated positively with F-FDG uptake in uterine fibroids (P<0.05); and (c) multivariate logistic regression analysis showed that only the number of fibroids was meaningfully correlated with F-FDG uptake in uterine fibroids (odds ratio=30.000, P<0.05). CONCLUSION: Uterine fibroids have a higher positive F-FDG uptake rate and highly variable SUVmax. The SUVmax is especially higher in younger and premenopausal patients. Multiple fibroids play a decisive role in the positive F-FDG uptake rate possibly because of the quantitative to qualitative changes in the effects of estrogen on the proliferation of uterine fibroids. PMID- 27281360 TI - Undifferentiated carcinoma with osteoclast-like giant cells of the ampullary region: Short term survival after pancreaticoduodenectomy. AB - INTRODUCTION: Undifferentiated carcinomas with osteoclast-like giant cells (UC OGCs) of the ampullary region are very rare, with only a few cases reported to date. The clinicopathological features, treatment options, and prognosis of UC OGCs are unclear. This report describes a patient with UC-OGCs of the ampullary region. PRESENTATION OF CASE: A 78-year-old male patient was admitted for epigastric pain and fever. Contrast-enhanced computed tomography revealed a 2.6 cm mass at the duodenal papilla. Duodenoscopy revealed a smooth red protruding mass compressing the orifice of the papilla of Vater. Biopsy of the mass showed proliferation of osteoclast-like giant cells. A subtotal stomach-preserving pancreaticoduodenectomy was performed, and the tumor was histologically diagnosed as an UC-OGCs of the ampullary region. Carcinoma in situ was also observed, spreading from the tumor at the terminal segment of the common bile duct to the common hepatic duct, with carcinoma cells at the surgical margin of the common hepatic duct. One year after surgery, the patient is alive and without tumor recurrence. DISCUSSION: UC-OGCs of the ampullary region is very rare neoplasm containing osteoclast-like giant cells and mononuclear cells. Osteoclast-like giant cells may originate from reactive mesenchymal cells and carcinoma in situ may spread to the common hepatic duct. Surgery including pancreaticoduodenectomy may be a treatment option for resectable tumors, whereas gemcitabine may be a treatment option for unresectable tumors. CONCLUSION: Carcinoma in situ may spread quite far (5cm) to the common hepatic duct, making it desirable to intraoperatively confirm negative bile duct margins by rapid pathologic diagnosis. PMID- 27281359 TI - Interim fluorine-18 fluorodeoxyglucose PET-computed tomography and cell of origin by immunohistochemistry predicts progression-free and overall survival in diffuse large B-cell lymphoma patients in the rituximab era. AB - OBJECTIVE: The aim of this study was to analyze the prognostic value of the interim PET (iPET)-computed tomography (CT) (iPET-CT) after two cycles of immunochemotherapy with the R-CHOP protocol in patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) treated with a curative intent in combination with the neoplastic cell origin defined by Hans's immunohistochemstry algorithm followed in a reference center for cancer treatment in Brazil. MATERIALS AND METHODS: We prospectively evaluated 147 DLBCL patients treated with R-CHOP-21 to assess the value of the International Prognostic Index, iPET-CT, and cell of origin by immunohistochemistry as prognostic markers in the rituximab era. Fluorine-18 fluorodeoxyglucose PET-CT was performed after two cycles (iPET-CT) and at the end of treatment in 111 patients. Lymphoma cases were categorized into germinal center (GC) and nongerminal center subtypes by immunohistochemistry according to Hans's algorithm. RESULTS: The median age of GC-DLBCL patients (52.7 years) was lower than that of nongerminal center-DLBCL patients (59.4 years) (P=0.021); in addition, it was lower in patients with negative iPET-CT findings (52.7 years) versus positive findings (59.4 years) (P=0.031). The overall survival at 48 months was 100% for iPET-CT-negative GC-DLBCL patients and 61.2% for iPET-CT-positive GC-DLBCL patients (P=0.002). Progression-free survival at 30 months was 100% for iPET-CT-negative GC-DLBCL patients and 60.3% for iPET-CT positive GC-DLBCL patients (P=0.001). CONCLUSION: We conclude that iPET-CT associated with cell origin identified a very good prognostic group in DLBCL patients treated with R-CHOP. Video Abstract: http://links.lww.com/NMC/A59. PMID- 27281361 TI - Breast sarcoma. A case report and review of literature. AB - INTRODUCTION: Breast sarcomas are rare with an annual incidence of 4.6 cases/1,000,000 women. They can appear as primary forms or secondary to radiation therapy or chronic lymphedema. PRESENTATION OF CASE: A 41 year old woman attended our hospital after having noticed an increase in the size of her fibroadenoma. The examination revealed a 7cm retroareolar nodule. Breast sonography described a hypoechoic bilobulated lesion and MRI showed a large size polinodular image, suggesting a Phyllodes tumor. A core needle biopsy was performed with a histological result of low-grade fusiform cells sarcoma on Phyllodes tumor so we proceeded to surgical treatment with a mastectomy. After two years and a half she noticed a tough nodule over the mastectomy scar, which was resected with a histological result of fusiform cells sarcoma. Considering the diagnosis of recurrence of the disease, surgery was undertaken. DISCUSSION: Breast sarcoma is a rare but aggressive entity. Core biopsy is the procedure of choice for the diagnosis. Lymphatic spread is uncommon so nodal status in breast sarcoma is less informative. Staging study differs from other breast tumors and chest computed tomography is helpful since lungs are the predominant metastatic sites. The use of radiotherapy or chemotherapy is controversial and will depend on the risk of tumor recurrence. CONCLUSION: Surgery represents the only potentially curative therapy for breast sarcoma. Tumor size and adequate resection margin are the most important prognostic factors. Approximately 80% of recurrences appear in the first two years. PMID- 27281362 TI - A case report of anorectal malignant melanoma with mucosal skipped lesion. AB - INTRODUCTION: We report our experience involving a case of relatively rare anorectal malignant melanoma with skipped lesion. PRESENTATION OF CASE: The patient was a 72-year-old man who had visited a local clinic complaining of a mass in the anal region, whereupon he was referred to our hospital on suspicion of a malignant melanoma. Close examination revealed a 25-mm black type 1 tumor one-third the size of the circumference of the anal canal and located externally to it. We performed transanal resection of the tumor and confirmed a diagnosis of malignant melanoma. Notably, multiple macular black lesions spaced away from the main lesion were observed during surgery in half of the circumference of the anal canal, from the tumor to the pectinate line. A biopsy of the area also revealed malignant melanoma; therefore, we performed abdominoperineal resection. Pathological diagnosis indicated a submucosal depth; the patient was thus diagnosed with T4 N2c M0 stage IIIb malignant melanoma and was followed on an outpatient basis. DISCUSSION: Patients with anorectal malignant melanoma have very poor prognoses owing to early lymph node metastasis and hematogenous metastasis. Our case illustrates that small anorectal malignant melanoma lesions can spread from the main lesion and invade the mucosa; examinations may sometimes miss such skipped lesions. CONCLUSION: Skipped lesions can occur in anorectal melanomas; thus, careful scrutiny of such lesions is required. Moreover, lesion resection is critical for anorectal malignant melanomas. PMID- 27281363 TI - Aggressive angiomyxoma presenting with back and perineal bulge; a complex surgical approach: A case report. AB - INTRODUCTION: Aggressive angiomyxoma is a rare mesenchymal tumor occurring predominantly in the pelvi-perineal region. It is more common in females during their reproductive age. Our focus is on the surgical approach for a recurrent angiomyxoma. CASE PRESENTATION: We present a case of a 36-year-old female patient with a recurrent lower back and perineal bulges. One year ago, she had the same presentation and underwent resection of that mass in a peripheral hospital without available information. Five months later, she started to have the same bulge. Computed tomography scan and true cut biopsy were suggestive of angiomyxoma with single lung metastasis. The decision was to proceed with resection through a transabdominal and perineal incision, even in the presence of metastasis since it's a very slow growing tumor with long life expectancy. The pathology was consistent with aggressive angiomyxoma. DISCUSSION: 90% of patients with angiomyxoma are women. Although it is benign, the tumor is still aggressive because of the high rate of local recurrence after resection. Angiomyxoma is a mesenchymal tumor, composed of fibroblasts within a myxoid background. Treatment is usually through wide local excision to achieve an R0 resection. Our approach was through a transabdominal and perineal incision, which allowed full control and mobilization of the tumor without disrupting the capsule. This surgical approach was not described previously in the literature. CONCLUSION: The principle to achieve cure in aggressive angiomyxoma is by optimizing exposure through two different incisions, wide excision while keeping the capsule intact and removing enbloc any invaded organ. PMID- 27281364 TI - Influenza Activity - United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine. AB - During the 2015-16 influenza season (October 4, 2015-May 21, 2016) in the United States, influenza activity* was lower and peaked later compared with the previous three seasons (2012-13, 2013-14, and 2014-15). Activity remained low from October 2015 until late December 2015 and peaked in mid-March 2016. During the most recent 18 influenza seasons (including this season), only two other seasons have peaked in March (2011-12 and 2005-06). Overall influenza activity was moderate this season, with a lower percentage of outpatient visits for influenza-like illness (ILI),(?) lower hospitalization rates, and a lower percentage of deaths attributed to pneumonia and influenza (P&I) compared with the preceding three seasons. Influenza A(H1N1)pdm09 viruses predominated overall, but influenza A(H3N2) viruses were more commonly identified from October to early December, and influenza B viruses were more commonly identified from mid-April through mid-May. The majority of viruses characterized this season were antigenically similar to the reference viruses representing the recommended components of the 2015-16 Northern Hemisphere influenza vaccine (1). This report summarizes influenza activity in the United States during the 2015-16 influenza season (October 4, 2015-May 21, 2016)(S) and reports the vaccine virus components recommended for the 2016-17 Northern Hemisphere influenza vaccines. PMID- 27281365 TI - Sodium Selenite as an Anticancer Agent. AB - Selenium (Se) is a ubiquitous, albeit not uniformly distributed metalloid present in earth crust. Consequently, its human intake with food products, particularly grains and vegetables, is also very uneven, and in certain cases can result in a severe Se deficiency. It was also documented that Se deficiency observed in some countries and/or geographic regions (e.g. Keshan region in China), is associated with an increased morbidity and mortality of neoplastic diseases. To correct this problem a number of organic and inorganic selenium compounds were developed and tested. However, it is now firmly established that only an inorganic sodium selenite with four-valent Se, and not that with six-valent (selenate) cation shows anticancer activity. This difference in their biological activities is due to their physicochemical properties. Thus selenite (Se+4) can undergo redox reaction, for example with protein's sulfhydryl groups expressed on the surface of tumor cells. In this way selenite prevents non-enzymatic formation of parafibrin that coats tumors cells and hence presents them as 'self' to the innate cellular immune system. Consequently, macrophages of the lymphatic system do not recognize neoplastic cells as 'foreign' bodies and spare them from the immune destruction. This mechanism can explain the failure of various immunotherapies to completely eliminate tumors from human bodies. Another contributing factor to carcinogenesis is the excessive consumption of red meat containing redox-active iron (Fe+3) that initiates parafibrin formation from blood fibrinogen. In conclusion, sodium selenite is a readily available and inexpensive drug of choice in the cancer treatment and prevention. PMID- 27281366 TI - Diazenyl Derivatives and their Complexes as Anticancer Agents. AB - In the past years, many diazenyl compounds (i.e diazenecarboxamides, diazeniumdiolate prodrugs, diazenyl complexes etc.) have been prepared for the evaluation of their cytotoxic potential towards various cancer cell lines. Majority of them have shown promising cytotoxic activities even against several drug resistant cell lines. These derivatives have shown their effect by acting as alkylating agents, releasers of cytotoxic NO, targeting receptors like tyrosine kinase, EGFR or targeting enzymes like GST, AGT, CDKs etc. Their interaction with different receptors or enzymes leads to DNA damage, necrosis or apoptosis resulting in cell death. The present review will cover updated information on the synthetic methodologies and cytotoxic potential of diazenyl derivatives developed during the past years along with the recent developments. This may prove to be helpful for the researchers to develop novel anticancer drugs in future by molecular modifications of potential derivatives with better cytotoxic activities. PMID- 27281367 TI - Plant Derived Inhibitor Sulforaphane in Combinatorial Therapy Against Therapeutically Challenging Pancreatic Cancer. AB - Pancreatic cancer is one of the most aggressive human cancers and is expected to surpass breast cancer to become the third chief cause of cancer-related deaths in the United States. While conventional treatment approaches such as surgery and classic chemotherapy have slightly improved the relative five year survival rate to 8% yet it is the lowest survival rate for any major cancer. This emphasizes the serious need of more effective and well tolerated therapies to reverse the poor prognosis of the defined neoplasm. Aberrant expression of histone deacetylase (HDAC) enzymes has been implicated in pancreatic cancer signalling. The inhibitors of these enzymes namely HDAC inhibitors (HDACi) are the novel agents which are currently being tested. These inhibitors modulate both histone and nonhistone proteins and have shown multiple biological effects including cell cycle arrest, differentiation and apoptosis in several cancer models. This article focuses on plant-derived HDAC inhibitor Sulforaphane (SFN) as a promising antipancreatic cancer agent. Moreover, we discuss the distinct molecular mechanisms triggered by SFN to exert cytotoxic effect in the predefined cancer models. Finally we describe the combinatorial therapeutic strategy involving SFN with other anticancer agents. This novel approach circumvents herculean cancer chemoresistance and alleviates toxicity, the main drawbacks of monotherapy. PMID- 27281368 TI - Measuring Physical Activity in Older Adults Using MotionWatch 8 Actigraphy: How Many Days are Needed? AB - Evidence suggests sleep and physical activity (PA) are associated with each other and dementia risk. Thus, identifying reliable methods to quantify sleep and PA concurrently in older adults is important. The MotionWatch 8(c) (MW8) wrist-worn actigraph provides reliable estimates of sleep quality via 14 days of measurement; however, the number of days needed to monitor PA by MW8 for reliable estimates is unknown. Thus, we investigated the number of days of MW8 wear required to assess PA in older adults. Ninety-five adults aged > 55 years wore MW8 for >= 14 days. Spearman-Brown analyses indicated the number of monitoring days needed for an ICC = 0.95 was 6-7 days for sedentary activity, 9-10 days for light activity, and 7-8 days for moderate-to-vigorous PA. These results indicate 14 days of MW8 monitoring provides reliable estimates for both sleep and PA. Thus, MW8 is ideal for future investigations requiring concurrent measures of both sleep quality and PA. PMID- 27281369 TI - Proapoptotic Activity of Propolis and Their Components on Human Tongue Squamous Cell Carcinoma Cell Line (CAL-27). AB - Propolis has been used since ancient times in folk medicine. It is a popular medicine possessing a broad spectrum of biological activities. This material is one of the richest sources of polyphenolic compounds such as flavonoids and phenolic acids. The ethanolic extract of propolis (EEP) evokes antibacterial, antiviral, antifungal and anticancer properties. Due to pharmacological properties it is used in the commercial production of nutritional supplements. In this study, gas chromatography coupled with mass spectrometry (GC-MS) was used to quantify main polyphenols in EEPs. The effect of EEPs, individual EEPs components (chrysin, galangin, pinocembrin, caffeic acid, p-coumaric acid, ferulic acid) and their mixture on viability of human tongue squamous cell carcinoma cell line (CAL 27) as well as the molecular mechanisms of the process were examined. The results of MTTs assay demonstrated that EEP, polyphenols and mixture of polyphenolic compounds were cytotoxic for CAL-27 cells in a dose dependent manner. The mechanism of cytotoxicity induced by these components undergoes through apoptosis as detected by flow cytometry. The ethanolic extracts of propolis activated caspases -3, -8, -9. Mixture of polyphenols was found as the most potent inducer of apoptosis thorough both intrinsic and extrinsic pathway. Therefore, we suggest that anticancer properties of propolis is related to synergistic activity of its main components. PMID- 27281370 TI - Sonographic evaluation of immobility of normal and endometriotic ovary in detection of deep endometriosis. AB - OBJECTIVES: To examine the association between ovarian immobility and presence of endometriomas and assess the diagnostic accuracy of transvaginal sonographic (TVS) ovarian immobility in the detection of deep infiltrating endometriosis (DIE). METHODS: This was a multicenter prospective observational study of women presenting with chronic pelvic pain from January 2009 to March 2015. Women with or without history of endometriosis who were scheduled to undergo laparoscopic surgery for endometriosis gave a detailed history and underwent specialized TVS in a tertiary referral unit prior to laparoscopy. During TVS, ovarian mobility and the presence of endometriomas were assessed. The relationship between TVS ovarian mobility, with or without endometriomas, and DIE was correlated with the gold standard, diagnosis of endometriosis at laparoscopy. RESULTS: Included in the analysis were 265 women with preoperative TVS and laparoscopic outcomes. Ovarian immobility on TVS was significantly associated with presence of endometriomas at surgery, with a prevalence of 12.2%, 10.8% and 52.7% for fixation of the left ovary only, the right ovary only and bilateral ovaries, respectively, compared with 4.2%, 3.7% and 7.3% for normal ovaries. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and positive and negative likelihood ratios of TVS ovarian immobility for diagnosis at surgery of immobility of ovaries with endometriomas in the left ovary only were 44.4%, 92.3%, 44.4%, 92.3%, 5.8, 0.6, in the right ovary only were 50.0%, 98.5%, 80.0%, 94.2%, 33.0, 0.5 and bilaterally were 74.4%, 68.6%, 72.5%, 70.6%, 2.4, 0.4, while those for diagnosis of immobility of normal ovaries were 25.0%, 87.9%, 8.3%, 96.4%, 2.1, 0.9 for left ovary only, 14.3%, 92.9%, 7.1%, 96.6%, 2.0, 0.9 for right ovary only and 35.7%, 97.2%, 50.0%, 95.0%, 12.6, 0.7 bilaterally, respectively (P < 0.05 except for normal left and right ovaries with P = 0.2 and 0.4, respectively). The sensitivity, specificity, PPV and NPV for performance of ovarian immobility in the prediction of DIE for all women were 58.3%, 74.1%, 60.6%, 72.2% and in the prediction of need for bowel surgery were 78.2%, 71.1%, 41.3%, 92.6%, respectively. CONCLUSIONS: There is a significant association between ovarian immobility and the presence of endometriomas. Ovarian immobility as a sonographic 'soft marker' of DIE performs better in the presence of endometriomas compared with in normal ovaries. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27281372 TI - Improving transparency and reproducibility through registration: The status of intervention trials published in clinical psychology journals. AB - OBJECTIVE: Prospective registration increases the validity of randomized controlled trials (RCTs). In the United States, registration is a legal requirement for drugs and devices regulated by the Food and Drug Administration (FDA), and many biomedical journals refuse to publish trials that are not registered. Trials in clinical psychology have not been subject to these requirements; it is unknown to what extent they are registered. METHOD: We searched the 25 highest-impact clinical psychology journals that published at least 1 RCT of a health-related psychological intervention in 2013. For included trials, we evaluated their registration status (prospective, retrospective, not registered) and the completeness of their outcome definitions. RESULTS: We identified 163 articles that reported 165 RCTs; 73 (44%) RCTs were registered, of which only 25 (15%) were registered prospectively. Of registered RCTs, only 42 (58%) indicated their registration status in the publication. Only 2 (1% of all trials) were registered prospectively and defined their primary outcomes completely. For the primary outcome(s), 72 (99%) of all registrations defined the domain, 67 (92%) the time frame, and 48 (66%) the specific measurements. Only 19 (26%) and 5 (7%) defined the specific metric and method of aggregation, respectively, for all primary outcomes. CONCLUSIONS: Very few reports of RCTs published in clinical psychology journals were registered prospectively and completely. Clinical psychology journals could improve transparency and reproducibility, as well as reduce bias, by requiring complete prospective trial registration for publication and by including trial registration numbers in all reports of RCTs. (PsycINFO Database Record PMID- 27281371 TI - Brief mindfulness training reduces salivary IL-6 and TNF-alpha in young women with depressive symptomatology. AB - OBJECTIVE: Pro-inflammatory cytokines have been implicated in the pathophysiology and maintenance of depression. This study investigated the effects of a brief mindfulness intervention on salivary pro-inflammatory correlates of depression (IL-6, TNF-alpha) and self-reported symptoms of depression in college women. METHODS: Sixty-four females with a cut score of >=16 on the Center for Epidemiological Studies for Depression Scale (CES-D) were assigned to a 4-week mindfulness-based intervention (MBI; N = 31) or a contact-control group (N = 33). For both groups, salivary cytokines and depressive symptoms were assessed at baseline and posttreatment. For the mindfulness group only, salivary cytokines were also assessed at a 3-month follow-up. RESULTS: Both groups showed similar reductions in depression. However, MBI (vs. control) predicted greater reductions in IL-6 and TNF-alpha; changes in IL-6 were sustained at 3-month follow-up. Higher baseline depressive symptoms predicted greater reductions in inflammation in the mindfulness group. CONCLUSION: MBIs may reduce inflammatory immune markers commonly implicated in depression. Individuals with greater depressive symptoms may benefit more from mindfulness training. Although reductions in salivary cytokines in the mindfulness condition were not attributable to changes in depressive symptoms, future work should examine the possibility that such reductions are protective against the development of future depressive episodes. (PsycINFO Database Record PMID- 27281373 TI - Treatment expectations for cognitive-behavioral therapy and light therapy for seasonal affective disorder: Change across treatment and relation to outcome. AB - OBJECTIVE: To examine the dynamic relationship between treatment expectations and treatment outcome over the course of a clinical trial for winter seasonal affective disorder (SAD). METHOD: Currently depressed adults with Major Depression, Recurrent with Seasonal Pattern (N = 177) were randomized to 6 weeks of group-delivered cognitive-behavioral therapy for SAD (CBT-SAD) or light therapy (LT). The majority were female (83.6%) and white (92.1%), with a mean age of 45.6 years. Treatment expectations for CBT-SAD and LT were assessed using a modification of the Treatment Expectancy and Credibility Survey (Borkovec & Nau, 1972). Depression severity was assessed using the Beck Depression Inventory Second Edition (Beck, Steer, & Brown, 1996). All measures were administered at pretreatment, midtreatment, and posttreatment. RESULTS: As treatment progressed, expectations for the treatment received increased across time steeply in CBT-SAD patients and moderately in LT patients. Collapsing across time, patients with higher treatment expectations had lower depression severity than those with lower treatment expectations. In a cross-lagged panel path analysis, there was a significant effect of treatment expectations at midtreatment on depression severity at posttreatment among CBT-SAD patients. CONCLUSIONS: Treatment expectations changed across treatment, affected outcome, and should be assessed and monitored repeatedly throughout treatment. Findings suggest that treatment expectations at midtreatment are a mechanism by which CBT-SAD reduces depression, which should be replicated in SAD samples and examined for generalizability to nonseasonal depression. These findings underscore the importance of further research examining treatment expectations in mediating CBT's effects in depression and other types of psychopathology. (PsycINFO Database Record PMID- 27281374 TI - Effects of attention control training on drug abusers' attentional bias and treatment outcome. AB - OBJECTIVE: Attentional bias for drug-related stimuli (Drug-AB) has been shown to play an important role in drug abuse, drug treatment, and relapse. This study sought to retrain Drug-AB using the Drug Attention Control Training Program (Drug ACTP) on a sample of Iranian drug abusers. METHOD: The experimental group (n = 24) received 3 sessions of training with the Drug-ACTP in addition to treatment as usual; the control group (n = 24) received only treatment as usual. All participants completed a demographic questionnaire, the drug-Stroop test, measures of physiological cue reactivity, the Personal Concerns Inventory (a measure of motivational structure), Persian Temptation Scale, Perceived Stress Scale (PSS), Positive Affect and Negative Affect Schedule (PANAS), Situational Confidence Questionnaire (SCQ), and Readiness to Change Questionnaire (RTCQ). All participants were tested at baseline, posttraining, and a 2-month follow-up. A brief, 6-month telephone follow-up was also conducted to monitor their temptation, SCQ, RTCQ, PANAS, and PSS scores; doses of medicine taken; and number of lapses. RESULTS: The results showed that, compared to the control group, the experimental group showed (a) reductions in Drug-AB, temptations to use, doses of medicine, and number of lapses; and (b) increases on the RTCQ and 2 subscales of the SCQ. Regardless of group membership, adaptive motivation was positively correlated with success in achieving therapeutic goals, and negatively associated with doses of methadone taken and number of relapses. CONCLUSIONS: It seems that attentional training can be an important addition to methadone maintenance therapy. (PsycINFO Database Record PMID- 27281375 TI - Neglected waterborne parasitic protozoa and their detection in water. AB - Outbreak incidents raise the question of whether the less frequent aetiological agents of outbreaks are really less frequent in water. Alternatively, waterborne transmission could be relevant, but the lack of attention and rapid, sensitive methods to recover and detect the exogenous stages in water may keep them under recognized. High quality information on the prevalence and detection of less frequent waterborne protozoa, such as Cyclospora cayetanensis, Toxoplasma gondii, Isospora belli, Balantidium coli, Blastocystis hominis, Entamoeba histolytica and other free-living amoebae (FLA), are not available. This present paper discusses the detection tools applied for the water surveillance of the neglected waterborne protozoa mentioned above and provides future perspectives. PMID- 27281376 TI - Factors Affecting Healthful Eating Among Touring Popular Musicians and Singers. AB - Maintaining good health is essential for touring musicians and singers. The stressful demands of touring may impact food choices, leading to detrimental effects on health and performance. This exploratory pilot study aimed to assess factors affecting healthful eating of touring musicians and singers. A 46-item survey was used to assess food- and nutrition-related attitudes, knowledge and behaviors, and environmental factors, as well as lifestyle, musical background, and demographic data. Participants (n=35) were recruited from a musicians' assistance foundation as well as touring musical theater productions and a music festival. Results indicate that touring musicians and singers had positive attitudes regarding healthful foods. Of 35 respondents, 80.0% indicated eating healthful food was important to them. Respondents reported feeling confident selecting (76.5%) and preparing (82.4%) healthful foods; however, they showed uncertainty when determining if carbohydrate-containing foods should be consumed or avoided. Respondents indicated environmental factors including availability and cost of healthy food options and tour schedules limited access to healthful foods. Venues (73.5%), fast food restaurants (67.6%), and airports (64.7%) were the most frequently identified locations in need of offering more healthful food choices. Respondents (52.9%) indicated more support from others while touring would help them make healthier food choices. More research is needed to develop mobile wellness programs as well as performance-based nutrition guidelines for musicians and singers that address the unique demands associated with touring. PMID- 27281377 TI - Inefficiencies in Motor Strategies of Horn Players with Embouchure Dystonia: Comparisons to Elite Performers. AB - OBJECTIVE: Motor control of the muscles of the face, lips, and tongue of horn players has traditionally been described from externally observed phenomena. Developments in real-time, high-speed magnetic resonance imaging (MRI) extend the scope of study to include descriptive and quantitative information from within the mouth. We employed these developments to compare oral movement strategies between 12 elite horn players and 5 horn players with embouchure dystonia (ED). METHODS: Serial images with an acquisition time of 33.3 ms were obtained from each subject as they performed 6 exercises on an MRI-compatible horn: 1) a slurred ascending harmonic sequence, 2) a slurred descending harmonic sequence, 3 6) sustained high and low notes, each performed softly and loudly. Temporal changes in pixel luminescence along a series of lines positioned within the oral cavity were calculated using a customized MATLAB toolkit. This allowed the extraction of temporal line profiles for comparative analyses between elite and dystonic horn players. RESULTS: Differing motor strategies of controlling the tongue and jaw were observed during ascending and descending exercises. In ascending exercises, the elite players employed a strategy of elevation and anterior tongue displacement and elevation of the jaw, whereas dystonic players exhibited more variability in their responses. With descending exercises, both groups exhibited a lowering of the tongue and jaw, though this was more pronounced and consistent in the elite horn players. Sustained note exercises also elicited differences between groups. We suggest that elite strategies are more efficient and that the less-efficient patterns of dystonic players may exacerbate muscular tension with ED. PMID- 27281378 TI - Playing-Related Musculoskeletal Problems Among Professional Orchestra Musicians in Scotland: A Prevalence Study Using a Validated Instrument, the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM). AB - Many epidemiological surveys on playing-related musculoskeletal problems (PRMPs) have been carried out on professional musicians, but none have evaluated or confirmed the psychometric properties of the instruments that were used. The aim of the present study was to evaluate the prevalence of PRMPs among professional orchestra musicians and to gather information on pain intensity and pain interference on function and psychosocial variables, using a self-report instrument developed and validated specifically for a population of professional orchestra musicians. METHODS: Out of 183 professional orchestra players, 101 took part in the study (55% response rate) and completed the Musculoskeletal Pain Intensity and Interference Questionnaire for Musicians (MPIIQM). RESULTS: Lifetime prevalence of PRMPs was 77.2%, 1-year prevalence was 45.5%, and point prevalence was 36.6%. Of the PRMP group, 43% reported having pain in three or more locations, most commonly the right upper limb, neck, and left forearm and elbow. However, predominant sites of PRMPs varied between instrument groups. The mean pain intensity score for the PRMP group was 12.4+/-7.63 (out of 40). The mean pain interference score was 15.2+/-12.39 (out of 50), increasing significantly with the number of reported pain locations (F=3.009, p=0.044). CONCLUSION: This study confirms that musculoskeletal complaints are common in elite professional musicians and that the use of an operational definition and a validated self-report instrument allows for more accurate and meaningful estimates of pain prevalence. PMID- 27281379 TI - Musculoskeletal Pain in Trombonists: Results from the UNT Trombone Health Survey. AB - The trombone is a popular, versatile, and unique member of the brass family of musical instruments. Yet the musculoskeletal health concerns of trombonists are grossly understudied. The purpose of this study was to develop and apply a novel online research strategy for assessing musical and non-musical demographics along with prevalence, frequency, intensity, quality, timing, and location of site specific trombone-related pain. Of the 316 trombonist respondents to this open survey, 76.6% (n=242) experienced trombone-related pain in one or more sites over the past year. Lip was the site with the highest prevalence rate for pain (23%). Selected pain sites were outlined in three primary clusters of musculoskeletal sites: 1) the lips and jaw region, 2) left upper extremity, and 3) back region. Over 35% (n=114) reported that trombone-related pain prevented playing their instrument. Site-specific characteristics of pain suggest that future epidemiologic studies seek to better understand location-specific intensity, frequency, quality, and timing of pain. Such details will assist educators, performers, and clinicians understand, prevent, and treat musculoskeletal problems associated with learning and performing musical instruments. PMID- 27281380 TI - Whole-Body Balance Regulation during the Turn Phase of Pique and Pirouette Turns with Varied Rotational Demands. AB - OBJECTIVE: To compare dancers' balance regulation at the whole-body level under increased rotational demands during the turn phase of turns with and without large center-of-mass (CM) translation (i.e., pique vs pirouette turns). METHODS: Ten dancers performed single and double pique and pirouette turns while kinematics and reaction forces were measured. During the turn phase, initial CM velocity, vertical alignment of the CM, mean braking force, and moment about the CM were compared across turn conditions using within-subject (Cliff's analog of Wilcoxon-Mann-Whitney test, adjusted for multiple comparisons) and group (sign test) statistical methods. RESULTS: For both single and double turns, the pique turn phase was initiated with a significantly larger CM velocity towards the base of support than during the pirouette, consistent with the mechanical objectives of the turn. Additionally, during the turn phases of both single and double turns, the CM during the pirouette turns was more vertically aligned with the base of support than it was during the pique turns. As rotational demand increased in both turns, the reaction forces were regulated in two ways to minimize the CM horizontal velocity as it approached vertical alignment with the base of support. By controlling the braking force and moment applied about the CM early during the turn phase, the potential for the CM to remain vertically aligned with the base of support increased. These findings can assist development of training tools geared towards balance regulation during pirouette and pique turns. PMID- 27281381 TI - Association Between Unstable Work and Occupational Wellbeing Among Artists in Finland: Results of a Psychosocial Survey. AB - OBJECTIVE: Although artistic work is in transition, the occupational wellbeing of artists has been less studied than wellbeing among other workers. This study aimed to explore the relationship between work characteristics and occupational (psychosocial) wellbeing of artists. METHODS: A national questionnaire was sent to all artists (theatre artists, writers, and visual artists) reached by four major labor unions in Finland. Type of employment (permanent full-time work vs other), working field (own field of art vs other), regularity of working hours (regular vs irregular), and control of workload were assessed. The wellbeing outcomes were work engagement, recovery from work, and experience of stress and low mood. RESULTS: Full-time permanent employment, regular working hours, and working in one's own field of art were positively associated with work engagement. Furthermore, regular working hours were positively associated with recovery and negatively associated with subjective report of low mood. Ability to control workload was positively associated with recovery and negatively associated with stress and low mood. Higher age was associated with lower stress and better recovery. CONCLUSIONS: Artists with regular working hours, secure employment, ability to control workload, working in one's own field of art, and higher age reported better wellbeing in this study. The late stages of career appear to guarantee more stability and wellbeing than the more insecure beginning of a career. PMID- 27281382 TI - Embouchure Dysfunction in Air Force Band Brass Musicians. AB - Occupational injuries and medical problems in musicians are well described, but relatively less attention has been paid to orofacial and embouchure-related problems in professional brass players. This study addressed embouchure-related problems in Air Force Band members, a population of musicians with an intense practice and performance schedule. METHODS: A survey was developed and distributed via the Air Force Survey Office to 599 active-duty Air Force Band members and 201 Air National Guard members. The survey assessed practice patterns, practice and performance venues, and presence of symptoms suggesting embouchure dysfunction. RESULTS: Responses were obtained from 167 Air Force Band brass players. Of the 157 responding to the question about embouchure dysfunction, 42% reported having experienced an embouchure problem at some point in the past, and 53% of those respondents reported that they were currently experiencing an embouchure problem. Forty-one percent of those with embouchure problems cited practice venues that were not conducive to effective and efficient practice at the time their embouchure problems began, and 48% of those with embouchure problems reported having to overblow in rehearsal at the time their problems began. DISCUSSION: Embouchure disorders were reported in a large proportion of Air Force Band brass survey respondents, and specific concerns related to practice venues and the need to overblow in practice settings suggest factors suitable to remediation and preventive strategies. PMID- 27281383 TI - In the June Issue. PMID- 27281384 TI - Pressure-Induced Conductivity in a Neutral Nonplanar Spin-Localized Radical. AB - There is a growing interest in the development of single-component molecular conductors based on neutral organic radicals that are mainly formed by delocalized planar radicals, such as phenalenyl or thiazolyl radicals. However, there are no examples of systems based on nonplanar and spin-localized C-centered radicals exhibiting electrical conductivity due to their large Coulomb energy (U) repulsion and narrow electronic bandwidth (W) that give rise to a Mott insulator behavior. Here we present a new type of nonplanar neutral radical conductor attained by linking a tetrathiafulvalene (TTF) donor unit to a neutral polychlorotriphenylmethyl radical (PTM) with the important feature that the TTF unit enhances the overlap between the radical molecules as a consequence of short intermolecular S...S interactions. This system becomes semiconducting upon the application of high pressure thanks to increased electronic bandwidth and charge reorganization opening the way to develop a new family of neutral radical conductors. PMID- 27281385 TI - An intergated serum and urinary metabonomic research based on UPLC-MS and therapeutic effects of Gushudan on prednisolone-induced osteoporosis rats. AB - Gushudan, a Chinese compound formulation based on the theory of traditional Chinese medicine and desgined to treat osteoporosis. However, its intergated intervention effective mechanism in vivo is not well understood. In this study, an intergated serum and urinary metabonomic strategy based on UPLC-MS technique have been developed to increase the understanding of the metabolism characters of osteoporosis and to investigate the holistic therapeutic efficacy of Gushudan on prednisolone-induced osteoporosis rat model. Principle component analysis (PCA) was utilized to identify differences in metabolic profiles of rats in the control group, prednisolone-induced osteoporosis model group and Gushudan-treatment group and clear separation was achieved among three groups. Furthermore, 17 potential biomarkers from urine and 10 potential biomarkers from serum were identified, primiarily related to amino acid metabolism, energy metabolism, lipid metabolism, intestinal flora metabolism and kidney damage. Gushudan has therapeutic effects on rat with osteoporosis via the regulation of multiple metabolic pathways. It's worth mentioning that some new biomarkers associated with osteoporosis such as 3 methoxydopa, 2,8-digydroxyadenine have been discovered in this study for the first time. This study provides a useful approach to get insight into the intergated metabonomic mechanism of prednisolone-induced osteoporosis and to assess the efficacy of Gushudan on osteoporotic rats. The work also shows that the metabonomics method is a promising tool in the efficacy and mechanism research of traditional Chinese compound medicines. PMID- 27281386 TI - Recessive Retinopathy Consequent on Mutant G-Protein beta Subunit 3 (GNB3). AB - IMPORTANCE: Mutations in phototransduction and retinal signaling genes are implicated in many retinopathies. To our knowledge, GNB3 encoding the G-protein beta subunit 3 (Gbeta3) has not previously been implicated in human disease. OBSERVATIONS: In this brief report, whole-exome sequencing was conducted on a patient with distinct inherited retinal disease presenting in childhood, with a phenotype characterized by nystagmus, normal retinal examination, and mild disturbance of the central macula on detailed retinal imaging. This sequencing revealed a homozygous GNB3 nonsense mutation (c.124C>T; p.Arg42Ter). Whole-exome sequencing was conducted from April 2015 to July 2015. CONCLUSIONS AND RELEVANCE: Expressed in cone photoreceptors and ON-bipolar cells, Gbeta3 is essential in phototransduction and ON-bipolar cell signaling. Knockout of Gnb3 in mice results in dysfunction of cone photoreceptors and ON-bipolar cells and a naturally occurring chicken mutation leads to retinal degeneration. Identification of further affected patients may allow description of the phenotypic and genotypic spectrum of disease associated with GNB3 retinopathy. PMID- 27281387 TI - Aripiprazole-Associated Hypoprolactinemia in the Clinical Setting. AB - BACKGROUND: The increase in prolactin (PRL) levels is a common adverse effect that occurs when using conventional and atypical antipsychotic drugs. Aripiprazole (ARI) is beneficial for antipsychotic-associated hyperprolactinemia but has been reported to decrease PRL secretion. Therefore, we investigated blood levels of PRL in patients who had taken ARI alone or in combination with other antipsychotics. METHODS: Retrospective information was obtained from 25 psychiatric patients who were prescribed ARI, and the blood levels of PRL were measured. RESULTS: The incidence of hypoprolactinemia in the current study was 44.0% (11/25). Eighteen patients were treated with ARI alone and 7 received ARI in combination with other antipsychotics. The PRL value of patients who took ARI alone was significantly lower than those who were also taking other antipsychotics (5.45 +/- 3.93 vs 10.85 +/- 5.53, P = 0.02; mean +/- SD). There was no significant correlation of the PRL levels and dose of ARI used in the 18 patients who had taken ARI alone. LIMITATIONS: This was a retrospective study, and the data were obtained from a small number of psychiatric patients treated with ARI. CONCLUSIONS: Monitoring of PRL levels in patients treated with ARI may be useful in minimizing hypoprolactinemia, which has the potential to negatively impact patients. In particular, hypoprolactinemia as a consequence of taking ARI should be discussed with patients of childbearing age and those with immune deficiencies. PMID- 27281388 TI - A Case of Sleepwalking With Sleep-Related Eating Associated With Ziprasidone Therapy in a Patient With Schizoaffective Disorder. PMID- 27281389 TI - Cataplexy Possibly Associated With Lamotrigine. PMID- 27281390 TI - Erratum, Vol. 13, May 26 Release. AB - [This corrects the article DOI: 10.5888/pcd13.150535.]. PMID- 27281391 TI - Perceived and Objective Measures of Neighborhood Environment for Physical Activity Among Mexican Adults, 2011. AB - INTRODUCTION: Environmental supports for physical activity may help residents to be physically active. However, such supports might not help if residents' perceptions of the built environment do not correspond with objective measures. We assessed the associations between objective and perceived measures of the built environment among adults in Cuernavaca, Mexico, and examined whether certain variables modified this relationship. METHODS: We conducted a population based (n = 645) study in 2011 that used objective (based on geographic information systems) and perceived (by questionnaire) measures of the following features of the built environment: residential density, mixed-land use, intersection density, and proximity to parks and transit stops. We used linear regression to assess the adjusted associations between these measures and to identify variables modifying these relationships. RESULTS: Adjusted associations were significant for all features (P < .05) except intersection density and proximity to transit stops. Significantly stronger associations between perceived and objective measures were observed among participants with low socioeconomic status, participants who did not own a motor vehicle or did not meet physical activity recommendations, and participants perceiving parks as safe. CONCLUSION: Perceived measures of residential density, mixed-land use, and proximity to parks are associated with objective environmental measures related to physical activity. However, in Mexico, it should not be assumed that perceived measures of intersection density and proximity to transit stops are the same as objective measures. Our results are consistent with those from high-income countries in that associations between perceived and objective measures are modified by individual sociodemographic and psychosocial factors. PMID- 27281392 TI - An Intervention to Increase Availability of Healthy Foods and Beverages in New York City Hospitals: The Healthy Hospital Food Initiative, 2010-2014. AB - BACKGROUND: Hospitals serve millions of meals and snacks each year; however, hospital food is often unhealthy. Hospitals are ideal settings for modeling healthy eating, but few programs have sought to improve nutrition in all venues where food is served. COMMUNITY CONTEXT: The New York City Department of Health and Mental Hygiene created the Healthy Hospital Food Initiative (HHFI) to improve the healthfulness of food served in hospitals. The HHFI built on prior work implementing mandatory nutrition standards for patient meals and vending in public hospitals. Public hospitals joined the HHFI by voluntarily adopting standards for cafeterias and cafes. Private hospitals joined by implementing nutrition standards for patient meals, food and beverage vending machines, and cafeterias and cafes. METHODS: Hospitals were recruited from 2010 through 2014 and provided technical assistance from health department staff. Implementation in each of the 4 areas was monitored through on-site assessments and menu review. Twenty-eight hospital cafeterias and cafes were evaluated at baseline and at the end of the HHFI to assess changes. OUTCOME: Sixteen public hospitals and 24 private hospitals joined the HHFI. Most (n = 18) private hospitals implemented standards in at least 2 areas. In cafeterias, most hospitals introduced a healthy value meal (n = 19), removed unhealthy items from the entrance and checkout (n = 18), increased whole grains to at least half of all grains served (n = 17), and reduced calories in pastries and desserts (n = 15). INTERPRETATION: Most New York City hospitals joined the HHFI and voluntarily adopted rigorous nutrition standards. Partnerships between hospitals and local government are feasible and can lead to significant improvements in hospital food environments. PMID- 27281395 TI - Gilead bets big on Nimbus' fatty liver disease drug. PMID- 27281394 TI - No guarantees in translation. PMID- 27281393 TI - Stability of a Split Streptomycin Binding Aptamer. PMID- 27281396 TI - Bristol-Myers Squibb locks into novel autoimmune strategy. PMID- 27281397 TI - Consortium nurtures ex vivo gene therapy firm. PMID- 27281398 TI - Matchmaker for NIH-rejected grants. PMID- 27281399 TI - Amgen/UCB build on bone franchise with anti-sclerostin antibody. PMID- 27281400 TI - White House unveils National Microbiome Initiative. PMID- 27281401 TI - CRISPR-edited crops free to enter market, skip regulation. PMID- 27281402 TI - Around the world in a month. PMID- 27281403 TI - Tech billionaires fund new cancer centers. PMID- 27281404 TI - AstraZeneca nabs genomics giants. PMID- 27281405 TI - First Rounders Podcast: Tom Maniatis. PMID- 27281406 TI - Research institute partnerships 2015. PMID- 27281407 TI - The president says patients should own their genetic data. He's wrong. PMID- 27281408 TI - Reply to Why patients shouldn't "own" their medical records. PMID- 27281409 TI - Why patients shouldn't "own" their medical records. PMID- 27281410 TI - Research that is fit to print. PMID- 27281411 TI - Secure cloud computing for genomic data. PMID- 27281412 TI - Reply to Research that is fit to print. PMID- 27281413 TI - The contribution of cell cycle to heterogeneity in single-cell RNA-seq data. PMID- 27281414 TI - Reply to The contribution of cell cycle to heterogeneity in single-cell RNA-seq data. PMID- 27281415 TI - Cancer moonshot countdown. PMID- 27281416 TI - Gene therapy's out-of-body experience. PMID- 27281417 TI - Biotech's wellspring-a survey of the health of the private sector in 2015. PMID- 27281418 TI - The morality and ethics governing CRISPR-Cas9 patents in China. PMID- 27281420 TI - Resistance from relatives. PMID- 27281421 TI - Comparing CRISPR and RNAi-based screening technologies. PMID- 27281422 TI - The minimal genome comes of age. PMID- 27281425 TI - Erratum: 20 years of Nature Biotechnology biomedical research. PMID- 27281424 TI - The US regulatory and pharmacopeia response to the global heparin contamination crisis. AB - The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration. PMID- 27281426 TI - Erratum: 20 years of Nature Biotechnology research tools. PMID- 27281427 TI - Erratum: Community crystal gazing. PMID- 27281428 TI - Corrigendum: Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates. PMID- 27281429 TI - Erratum: When biotech goes bad. PMID- 27281430 TI - Compensation inflation remains consistent at private life science companies. PMID- 27281432 TI - Aggregation and removal of copper oxide (CuO) nanoparticles in wastewater environment and their effects on the microbial activities of wastewater biofilms. AB - The transport behaviors of copper oxide (CuO) NPs in wastewater matrix and their possible impacts on microbial activities of stable wastewater biofilms cultivated in a lab scale rotating biological contactor (RBC) were investigated. Significant aggregation of CuO NPs was observed in the wastewater samples, depending on their mass concentrations. Extracellular polymeric substance (EPS)-adsorbed copper accounted for a large proportion of the total copper accumulated in biofilms. The microelectrode profiles showed that a single pulse exposure to 50mg/L CuO resulted in a deeper penetration depth of oxygen in biofilms compared to the CuO NP free biofilms. The maximum oxygen consumption rate shifted to the deeper parts of biofilms, indicating that the respiration activities of bacteria in the top region of the biofilms was significantly inhibited by CuO NPs. Biofilms secreted more EPS in response to the nano-CuO stress, with higher production of proteins compared to polysaccharides. PMID- 27281433 TI - Dynamic effect of leachate recirculation on batch mode solid state anaerobic digestion: Influence of recirculated volume, leachate to substrate ratio and recirculation periodicity. AB - Performances of batch mode solid state anaerobic digestion (SSAD) were investigated through several leachate recirculation strategies. Three parameters were shown to particularly influence methane production rates (MPR) and methane yields: the length of the interval between two recirculation events, the leachate to substrate (L:S) ratio and the volume of leachate recirculated. A central composite factor design was used to determine the influence of each parameter on methane production. Results showed that lengthening the interval between two recirculation events reduced methane yield. This effect can be counteracted by recirculating a large volume of leachate at a low L:S ratio. Steady methane production can be obtained by recirculating small amounts of leachate, and by lengthening the interval between two recirculations, regardless of the L:S ratio. However, several combinations of these parameters led to similar performances meaning that leachate recirculation practices can be modified as required by the specific constraints SSAD plants configurations. PMID- 27281434 TI - Optimizing granules size distribution for aerobic granular sludge stability: Effect of a novel funnel-shaped internals on hydraulic shear stress. AB - A novel funnel-shaped internals was proposed to enhance the stability and pollutant removal performance of an aerobic granular process by optimizing granule size distribution. Results showed up to 68.3+/-1.4% of granules in novel reactor (R1) were situated in optimal size range (700-1900MUm) compared to less than 29.7+/-1.1% in conventional reactor (R2), and overgrowth of large granules was effectively suppressed without requiring additional energy. Consequently, higher total nitrogen (TN) removal (81.6+/-2.1%) achieved in R1 than in R2 (48.1+/-2.7%). Hydraulic analysis revealed the existence of selectively assigning hydraulic pressure in R1. The total shear rate (tautotal) on large granules was 3.07+/-0.14 times higher than that of R2, while tautotal of small granules in R1 was 70.7+/-4.6% in R2. Furthermore, large granules in R1 with intact extracellular polymeric substances (EPS) outer layer structure entrapped hydroxyapatite at center, which formed a core structure and further enhanced the stability of aerobic granules. PMID- 27281435 TI - Germanium-Based Nanomaterials for Rechargeable Batteries. AB - Germanium-based nanomaterials have emerged as important candidates for next generation energy-storage devices owing to their unique chemical and physical properties. In this Review, we provide a review of the current state-of-the-art in germanium-based materials design, synthesis, processing, and application in battery technology. The most recent advances in the area of Ge-based nanocomposite electrode materials and electrolytes for solid-state batteries are summarized. The limitations of Ge-based materials for energy-storage applications are discussed, and potential research directions are also presented with an emphasis on commercial products and theoretical investigations. PMID- 27281436 TI - Biomolecular Interactions and Biological Responses of Emerging Two-Dimensional Materials and Aromatic Amino Acid Complexes. AB - The present work experimentally investigates the interaction of aromatic amino acids viz., tyrosine, tryptophan, and phenylalnine with novel two-dimensional (2D) materials including graphene, graphene oxide (GO), and boron nitride (BN). Photoluminescence, micro-Raman spectroscopy, and cyclic voltammetry were employed to investigate the nature of interactions and possible charge transfer between 2D materials and amino acids. Graphene and GO were found to interact strongly with aromatic amino acids through pi-pi stacking, charge transfer, and H-bonding. Particularly, it was observed that both physi and chemisorption are prominent in the interactions of GO/graphene with phenylalanine and tryptophan while tyrosine exhibited strong chemisorption on graphene and GO. In contrast, BN exhibited little or no interactions, which could be attributed to localized pi-electron clouds around N atoms in BN lattice. Lastly, the adsorption of amino acids on 2D materials was observed to considerably change their biological response in terms of reactive oxygen species generation. More importantly, these changes in the biological response followed the same trends observed in the physi and chemisorption measurements. PMID- 27281437 TI - Phosphorus(V) corrole: DNA binding, photonuclease activity and cytotoxicity toward tumor cells. AB - A new phosphorus(V) corrole, 10-(4-hydroxylphenyl)-5,15 bis(pentafluorophenyl)corrolato (trans-dihydroxo)phosphorus(V) 1-P, was synthesized and characterized. The interaction of 1-P with calf thymus DNA (CT DNA) was studied by multi-spectroscopic methods. The photonuclease activity of this complex was examined by agarose gel electrophoresis. 1-P may bind to CT-DNA via an outside binding mode and display good photonuclease activity. 1-P displayed low dark toxicity but high photocytotoxic activity against H460 and A549 tumor cell lines. PMID- 27281438 TI - Air-Stable Triazine-Based Ni(II) PNP Pincer Complexes As Catalysts for the Suzuki Miyaura Cross-Coupling. AB - Air-stable, thermally robust, and well-defined cationic Ni(II) PNP pincer complexes based on the 2,4-diaminotriazine scaffold are described. These complexes are active catalysts for the Suzuki-Miyaura cross-coupling of a wide range of aryl, heteroaryl (including benzoxazole, thiazole, pyridine, pyrimidine, thiazole), primary and secondary alkyl halides, and pseudohalides with different organoboronate reagents giving excellent to good isolated yields. Neutral deprotonated complexes seem to play a key role in the catalytic process. PMID- 27281439 TI - (1)H NMR-Based Metabolomics Reveals a Pedoclimatic Metabolic Imprinting in Ready to-Drink Carrot Juices. AB - Carrots are usually consumed in their native form or processed into many different products. Carrot juice is a popular beverage consumed throughout the world and is attracting increasing attention due to its nutritional value, being a natural source of bioactive compounds. Ready-to-drink carrot juices produced in the same factory were analyzed by (1)H nuclear magnetic resonance (NMR) spectroscopy. The juices were made from carrot roots of the same cultivar grown in three different geographical areas in Italy. More than 30 compounds have been identified and quantified, and the data was subjected to univariate ANOVA and multivariate analyses. Clear geographical-dependent clustering was observed, and the metabolic profiles were related to the different pedoclimatic conditions. The proposed phytoprofiling approach could be employed on an industrial scale to evaluate finished products involving different sites of supply of the raw material, thus improving both the quality and uniformity of the juices. PMID- 27281441 TI - Kawasaki Disease: An Autopsy Case Series and Review of the Literature. AB - INTRODUCTION: Kawasaki disease (KD) is a major cause of acquired heart disease in children, and there is limited information on postmortem findings in the pediatric population in Canada. CASES: For a 15-year time span (January 2000 March 2015), we had 2 cases of KD presented to the Department of Forensic Pathology at Hamilton General Hospital. DISCUSSION: There were common cardiac findings including presence of giant coronary artery aneurysms and microscopic changes occurring within the coronary arteries and the myocardium. Evidence of old infarction was present in both heart specimens, but acute infarction was noted in one of the specimens. CONCLUSIONS: This case series documents postmortem findings that outline cardiac complications of KD including aneurysms, thrombotic events, and infarcts. In addition to addressing the medical complications of KD, it is also important to address the psychosocial effect due to its impact on quality of life. PMID- 27281440 TI - Cost of Medications Recommended by Canadian Acne Clinical Practice Guidelines. AB - BACKGROUND: Acne affects a large proportion of the Canadian population and has psychosocial and financial consequences. OBJECTIVE: We provide cost information for treatments recommended by the Canadian acne guidelines. METHODS: Highest level recommendations were selected for 3-month usage cost. RESULTS: Three-month estimated treatment costs were as follows: topical retinoids ($14.40-$73.80), benzoyl peroxide (BPO; $6.75), fixed-dose BPO-clindamycin ($40.95-$44.10) and BPO adapalene ($73.80), oral antibiotics ($25.20 for tetracycline 250 mg qid; $52.20 and $52.74 for doxycycline 50 mg bid and 100 mg od, respectively), and hormonal therapy ($26.46-$37.80 for ethinyl estradiol [EE] 0.030 mg/drospirenone 3mg and $75.60-108.99 for EE 0.035 mg/cyproterone acetate 2 mg). Oral isotretinoin 3 month costs ranged from $393.96 to $478.80. CONCLUSIONS: Awareness of costs of recommended treatments may facilitate improved outcomes by increasing procurement and adherence. PMID- 27281442 TI - Hanging Deaths: A Retrospective Study Regarding 260 Cases. AB - Hanging is a form of asphyxia caused by external pressure on the upper airways deriving from a band tightened by the gravitational weight of the body. During a 33-year period from 1983 to 2015, there were 260 hanging deaths examined at the Brescia Institute of Forensic Medicine (Northern Italy), which represented approximately 40% of all the asphyxial deaths recorded during this period. Almost all of the cases were represented by suicidal events, 1 case was a homicide event and there also was a case of sexual asphyxia. Eighty-two percent of the victims were men; 18% were women. There was an increasing tendency in the ages between 20 and 60 years, and the highest number of cases was observed in the 41- to 50-year age group (23% of the cases). The most common place chosen by the victim was the home setting followed by isolated outdoor places. The most common ligature material was a rope. The pathological findings were evaluated in all cases. PMID- 27281443 TI - Court Decisions on Medical Malpractice in China After the New Tort Liability Law. AB - A new Tort Law of the People's Republic of China became effective on July 1, 2010. We undertook an analysis of medical malpractice lawsuits brought before regional courts in Beijing districts after this new Tort Liability Law went into effect. In total, 726 cases eventuating in a final verdict were collected from the Beijing district courts from 2011 to 2013 in this retrospective study; 83.7% of the 726 alleged instances of medical malpractice were confirmed to be malpractice by the final verdict. The disciplines most frequently involved with claims of medical malpractice were obstetrics and gynecology, the most frequent outcomes was death, and the most common types of case associated with malpractice was surgery related. The average length of time between the occurrence of the injury and closure of the claim was 9.2 months, and the average payment was Y163,000. Since the introduction of the new Tort Liability Law, the average time to complete a litigation was shortened, but it has made little apparent difference otherwise. PMID- 27281444 TI - Happy Now, Tired Later? Extraverted and Conscientious Behavior Are Related to Immediate Mood Gains, but to Later Fatigue. AB - OBJECTIVE: Experience sampling studies on Big Five-related behavior show that people display the whole spectrum of each trait in their daily behavior, and that desirable Big Five states-especially state Extraversion-are related to positive mood. However, other research lines suggest that extraverted and conscientious behavior may be mentally depleting. The present research examined this possibility by extending the time frame of the measured personality processes. METHOD: A 12-day experience sampling study (N = 48; observations = 2,328) measured Big Five states, mood, stress, and fatigue five times a day. RESULTS: Extraverted and conscientious behavior were concurrently related to positive mood and lower fatigue, but to higher fatigue after a 3-hour delay. These relations were not moderated by personality traits. The relation between extraverted behavior and delayed fatigue was mediated by the number of people the person had encountered. Whether the person had a goal mediated the relation between conscientious behavior and delayed fatigue. CONCLUSION: Extraverted and conscientious behavior predict mental depletion after a 3-hour delay. The results help reconcile previous findings regarding the consequences of state Extraversion and provide novel information about the consequences of state Conscientiousness. PMID- 27281445 TI - The Effect of Prednisolone on miR 15a and miR16-1 Expression Levels and Apoptosis in Acute Lymphoblastic Leukemia Cell Line: CCRF-CEM. AB - BACKGROUND: Glucocorticoids are probably the most important drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). Prednisolone exerts its effect by induce apoptosis in lymphoid lineage cells. Micro RNAs are 18-24 nucleotides RNA implicated in the control of essential biological functions, including apoptosis. In the following study, the effect of prednisolone on the expression of miR 15a & miR16-1 and apoptosis in the CCRF-CEM cell line is investigated. METHODS: The cell line of CCRF-CEM was cultured in standard conditions. The changes in the miR 15a and miR 16-1 expression levels were determined by Real Time-PCR technique. Also, the apoptosis is evaluated by flow cytometry using Annexin V and PI staining. RESULTS: This study revealed that, the prednisolone induced apoptosis in a time dependent manner. Prednisolone in concentration of 700 uM was significantly increased the expression of miR 16-1 and miR 15a after 24 h and 48 h treatment (p<0.05). CONCLUSION: prednisolone induced apoptosis might be mediated by up-regulation of these 2 miRNAs in CCRF CEM cells. PMID- 27281446 TI - Reversible Anti-Spermatogenic Effect of Piperine on Epididymis and Seminal Vesicles of Albino Rats. AB - BACKGROUND: We have recently proved the interactions of piperine with androgen receptor and androgen binding protein. The present study was aimed to evaluate the antifertility effect of piperine on male albino rats after the treatment period i. e., after 60 days and withdrawal period i. e., after 120 days. MATERIALS AND METHODS: Adult male rats were divided into 4 groups (n=12). Group I: CONTROL: Rats were given vehicle p.o i. e., 0.5% carboxy methyl cellulose (CMC) in normal saline daily for 60 days, Group II: Rats were treated with piperine suspended in 0.5% CMC at a dose of 10 mg/kg daily/60 days. Group III: Rats were treated with piperine suspended in 0.5% CMC at a dose of 10 mg/kg on every 4(th) day for 60 days. Group IV: Rats were treated with piperine suspended in 0.5% CMC at a dose of 10 mg/kg on every 7(th) day for 60 days. RESULTS: Piperine significantly altered the epididymal sperm count, motility, viability, weight of the epididymis, cauda, caput, corpus and seminal vesicles. It also exhibited negative impact on biochemical markers via decreasing epididymal sialic acid levels, seminal fructose content, epididymal anti-oxidant enzyme activities of super oxide dismutase (SOD), catalase (CAT) and by increasing the malondialdehyde content after the treatment period. Histopathological observations also supported the above findings. All the altered values were reinforced after the withdrawal period. CONCLUSION: From the results of this study, we can conclude that piperine has the potential to become a good lead for the reversible male oral contraceptive research. PMID- 27281447 TI - LC-MS Guided Isolation of Bioactive Principles from Iris hookeriana and Bioevaluation of Isolates for Antimicrobial and Antioxidant Activities. AB - The genus Iris is diverse both in the abundance of secondary metabolities as well as the biological activities. The rhizomes of Iris hookeriana exhibit significant anthelminthic activity against gastrointestinal nematodes of sheep. Although Iris hookeriana has been a subject of the study of so many phytochemical studies, yet we report some constituents for the first time from this plant using a different isolation approach. This manuscript presents the isolation, antimicrobial and antioxidant evaluation of bioactive principles from Iris hookeriana. LC-MS guided isolation technique was applied for the separation of target constituents. The isolates were characterised by spectral techniques and subjected to antioxidant evaluation by DPPH assay. Four compounds; resveratrol, resveratroloside, junipeginin C and isorhamnetin-3-O-neohesperidoside were isolated for the first time along with 3 known compounds viz piceid, irigenin and iridin from I. hookeriana using this approach. The antioxidant activity screening of the isolates revealed that all the 4 constituents isolated for the first time, have strong antioxidant potential with IC50 of 14.0 ug/ml (resveratroloside), 19.7 ug/ml (junipeginen C), 12.8 ug/ml (resveratrol) and 19.8 ug/ml (isorhamnetin-3-O neohesperodoside). So it can be safely concluded that LC-MS guided isolation of chemical compounds from Iris hookeriana has furnished 4 antioxidant constituents. Thus Iris hookeriana can act as as a good source of wonder molecule resveratrol and its 2 glycosides, resveratrolside and piceid which upon hydrolysis can be converted into the parent drug resveratrol. PMID- 27281448 TI - Efficacy and Safety of Ambroxol Lozenges in the Treatment of Acute Uncomplicated Sore Throat - a Pooled Analysis. AB - A pooled analysis is presented of 7 placebo-controlled RCT that investigated lozenges containing ambroxol for pain relief in acute sore throat.2 242 patients were treated with different ambroxol doses or control treatments, 2 183 were evaluable for efficacy. The present analysis is focused on the recommended dose of 20 mg (AXL20): 856 patients were treated with AXL20, 847 with matched placebo lozenges (PL).The average reduction in pain intensity over the first 3 h after the first AXL20 ranged from 38% to 52% of the maximum achievable effect (MAE). The overall treatment difference between AXL20 and PL was 11% (95% CI: 8-13%) of the MAE (post-hoc meta-analysis). The corresponding NNT was 6.0 (CI: 4.7-8.4) for an average pain reduction from baseline of 33% of the MAE over the first 3 h.71.9, 79.0, and 85.3% of the AXL20-patients scored the efficacy as "very good or good" at the end of the 1(st), 2(nd) and 3(rd) day, respectively, vs. 57.5, 64.4, and 70.4% of the PL-patients resulting in odds ratios of 1.9 (CI: 1.5-2.3) for the 1(st), 2.1 (CI: 1.7-2.6) for the 2(nd) and 2.43 (CI: 1.8-3.3) for the 3(rd) day.At the end of treatment 'no redness' or 'slightly red' was scored on pharyngeal inspection in 84.4% and 77.3% of AXL20- and PL-patients (OR: 1.6, CI: 1.3-1.9).AXL20-treatment was well tolerated and is safe and efficacious for acute uncomplicated sore throat of recent onset in adolescent and adult patients. PMID- 27281449 TI - Ultrafast Nonlinear Excitation Dynamics of Black Phosphorus Nanosheets from Visible to Mid-Infrared. AB - The recent progress on black phosphorus makes it a promising candidate material for broadband nanophotonic devices, especially operating in the mid-infrared spectral region. Here, the excited carrier dynamics and nonlinear optical response of unoxidized black phosphorus nanosheets and their wavelength dependence were systematically studied from 800 nm to 2.1 MUm. The wavelength dependent relaxation times of black phosphorus nanosheets are determined to be 360 fs to 1.36 ps with photon energies from 1.55 to 0.61 eV. In a comparative study with graphene, we found that black phosphorus has a faster carrier relaxation in near- and mid-infrared region. With regard to nonlinear optical absorption, the response of black phosphorus significantly increases from near- to mid-infrared, and black phosphorus is also confirmed to be better as saturable absorber to MoS2 in infrared region. PMID- 27281450 TI - A Selenium-Containing Diarylamido Pincer Ligand: Synthesis and Coordination Chemistry with Group 10 Metals. AB - The synthesis of new bifunctional organoselenium diarylamine compounds RN(4-Me-2 SeMe-C6H3)2 (R = Me: 1; R = tert-butoxycarbonyl (Boc): 2; R = H: 3-H) via aryllithium chemistry is disclosed. Compound 1 serves as a Se,Se-bidentate neutral ligand toward Pd(II), forming the coordination complex {PdCl2[MeN(4-Me-2 SeMe-C6H3)2-kappa(2)Se)]} (1-Pd) in reaction with [PdCl2(COD)] (COD = 1,5 cyclooctadiene), while the protio ligand 3-H forms tridentate pincer complexes [MCl(N(4-Me-2-SeMe-C6H3)2)] (M = Pd: 3-Pd; M = Pt: 3-Pt) with [MCl2(COD)] (M = Pd, Pt) in the presence of triethylamine. Complex 1-Pd does not undergo N-C cleavage at high temperature, unlike related alkylphosphine-bearing complexes. All compounds have been characterized by multinuclear ((1)H, (13)C, (77)Se) NMR spectroscopy, and crystal structures of 1, 1-Pd, 3-Pd, and 3-Pt are reported. Additionally, density functional theory calculations have been performed on the pincer complexes to contrast them with well-known analogues containing phosphine donor groups. PMID- 27281451 TI - Serum progranulin levels are elevated in patients with chronic hepatitis B virus infection, reflecting viral load. AB - Progranulin (PGRN) is implicated in infection, immunity and host defense, but its role in the pathogenesis of HBV infection remains unknown. Here we investigated whether there is dysregulated production and the clinical significance of circulating PGRN in patients with chronic HBV infection. Serum concentrations of PGRN were analyzed by enzyme-linked immunosorbent assay. Serum PGRN levels were significantly higher in patients with chronic HBV infection than healthy subjects. PGRN levels were significantly associated with HBV-DNA levels, but did not correlate with the concentrations of alanine aminotransferase and aspartate aminotransferase. This study demonstrates increased circulating PGRN production and association between PGRN levels and viral loads in patients with chronic HBV infection, suggesting a functional role of PGRN in the pathogenesis of HBV infection. PMID- 27281453 TI - Young adults with paediatric liver disease: future challenges. PMID- 27281452 TI - Impact of elicited mood on movement expressivity during a fitness task. AB - The purpose of the present study was to evaluate the impact of four mood conditions (control, positive, negative, aroused) on movement expressivity during a fitness task. Motion capture data from twenty individuals were recorded as they performed a predefined motion sequence. Moods were elicited using task-specific scenarii to keep a valid context. Movement qualities inspired by Effort-Shape framework (Laban & Ullmann, 1971) were computed (i.e., Impulsiveness, Energy, Directness, Jerkiness and Expansiveness). A reduced number of computed features from each movement quality was selected via Principal Component Analyses. Analyses of variance and Generalized Linear Mixed Models were used to identify movement characteristics discriminating the four mood conditions. The aroused mood condition was strongly associated with increased mean Energy compared to the three other conditions. The positive and negative mood conditions showed more subtle differences interpreted as a result of their moderate activation level. Positive mood was associated with more impulsive movements and negative mood was associated with more tense movements (i.e., reduced variability and increased Jerkiness). Findings evidence the key role of movement qualities in capturing motion signatures of moods and highlight the importance of task context in their interpretations. PMID- 27281454 TI - Failure to evaluate introduction of female genital mutilation mandatory reporting. PMID- 27281455 TI - Retrospective study of imported falciparum malaria in French paediatric intensive care units. AB - OBJECTIVE: The World Health Organization (WHO) severity criteria for paediatric Plasmodium falciparum (Pf) malaria are based on studies in countries of endemic malaria. The relevance of these criteria for other countries remains unclear. We assessed the relevance of these criteria in an industrialised country. DESIGN: Retrospective case-control study. SETTING: Eight French university hospitals, from 2006 to 2012. PATIENTS: Children with Pf malaria admitted to paediatric intensive care units (cases: n=55) or paediatric emergency departments (controls: n=110). MAIN OUTCOME MEASURES: Descriptive analysis of WHO severity criteria and major interventions (mechanical ventilation, blood transfusion, fluid challenge, treatment of cerebral oedema, renal replacement therapy). Thresholds were set by receiver operating characteristics curve analysis. RESULTS: Altered consciousness (71% vs 5%), shock (24% vs 1%), renal failure (20% vs 1%), anaemia <50 g/L (7% vs 2%), acidosis (38% vs 0%), bilirubin level >50 umol/L (25% vs 8%) and parasitaemia >10% (30% vs 8%) were more frequent in cases (p<0.01). All these criteria were associated with major interventions (p<0.001). Respiratory distress (six cases), and hypoglycaemia (two cases) were infrequent. Thrombocytopenia <50 000/mm3 (46% vs 7%) and anaemia (haemoglobin concentration <70 g/L (41% vs 13%)) were more frequent in cases (p<0.0001). CONCLUSIONS: The WHO severity criteria for paediatric Pf malaria are relevant for countries without endemic malaria. The infrequent but severe complications also provide a timely reminder of the morbidity and mortality associated with this condition worldwide. In non-endemic countries haemoglobin <70 g/L and platelet count <50 000/mm3 could be used as additional criteria to identify children needing high level of care. PMID- 27281456 TI - Extending Health and Safety to Informal Workers: A Photo Essay. PMID- 27281457 TI - Regioselective Hydrolysis and Transesterification of Dimethyl 3 Benzamidophthalates Assisted by a Neighboring Amide Group. AB - An efficient, highly regioselective hydrolysis and transesterification of dimethyl 3-benzamidophthalates into the corresponding carboxylic acid monoesters and mixed esters (including tert-butyl esters) under basic conditions is presented. The selectivity is governed by the neighboring 3-benzamido moiety's participation and by the nature of the solvent. In alcohols the reaction occurred exclusively at the ortho-position to the benzamido functionality, in pyridine or acetonitrile at both ester groups. An insight into the mechanistic pathway was obtained from a (1)H NMR study in perdeuteromethanol. PMID- 27281458 TI - Surface display of bacterial tyrosinase on spores of Bacillus subtilis using CotE as an anchor protein. AB - Tyrosinases, copper-containing monooxygenases, are widely used enzymes for industrial, medical, and environmental applications. We report the first functional surface display of Bacillus megaterium tyrosinase on Bacillus subtilis spores using CotE as an anchor protein. Flow Cytometry was used to verify surface expression of tyrosinase on the purified spores. Moreover, tyrosinase activity of the displayed enzyme on B. subtilis spores was monitored in the presence of L tyrosine (substrate) and CuSO4 (inducer). The stability of the spore-displayed tyrosinase was then evaluated after 15 days maintenance of the spores at room temperature, and no significant decrease in the enzyme activity was observed. In addition, the tyrosinase-expressing spores could be repeatedly used with 62% retained enzymatic activity after six times washing with Tris-HCl buffer. This genetically immobilized tyrosinase on the spores would make a new advance in industrial, medical, and environmental applications. PMID- 27281460 TI - What Unites Us in Death. PMID- 27281463 TI - De Novo Design of New Inhibitor of Mutated Tyrosine-Kinase for the Myeloid Leukemia Treatment. AB - BACKGROUND: Chronic myelogenous leukemia is associated with hematopoietic stem cells that are manifested primarily with expansion myelopoiesis. It is the first cancer directly associated with a genetic abnormality. Specifically, it is associated to a particular cytogenetic abnormality, known as Philadelphia chromosome (Ph), which results from a fusion between part of the BCR ("breakpoint cluster region") gene from chromosome 22 and the Abelson (ABL) gene on chromosome 9 and leads to the formation a new gene leukemia-specific, the BCR-ABL. Since 2011, there are several tyrosine-kinase inhibitors in the market. Due to mutations in the tyrosine-kinase domain, these inhibitors are becoming less effective in the leukemia treatment, and then there is a need for new more effective inhibitors. METHODS: The aim of this work is to obtain new tyrosine kinase inhibitors using in silico tools like de novo drug design, docking and absorption, distribution, metabolism and excretion studies. RESULTS: Using the proposed methodology, an initial library of more than 6000 molecules was obtained. This library was then filtered out using the Tanimoto metric to compute the similarity between the molecules using as parameter the 2D linear hashed fingerprint with a 64-bit address space. The resulting library was then used to run docking studies together with the reference market drugs and their ADME (absorption, distribution, metabolism and excretion) properties were determined. Three compounds with better inhibition capacity and better ADME properties that the commercially available not only for the wild form of enzymes under study but also to its mutated forms were obtained. CONCLUSION: The fragment based drug design method used in this work turns to be a good alternative to create new drugs that can control this neoplasm. Based on the calculated GScore, the de novo designed molecules have better inhibitor capacity than the tyrosine-kinase inhibitors most used in the market. These molecules shown strong potential to become drugs capable to inhibit all mutations, mainly the T315I mutation, now the leading cause of deaths due to the difficulty of inhibitors to control it. PMID- 27281464 TI - Boundary extension: Insights from signal detection theory. AB - After viewing a scene, people often remember having seen more of the world than was originally visible, an error referred to as boundary extension. Despite the large number of studies on this phenomenon, performance has never been considered in terms of signal detection theory (SDT). We report two visual memory experiments that allowed us to explore boundary extension in terms of SDT. In our experiments, participants first studied pictures presented as close-up or wide angle views. At test, either the identical view or a different view (a closer or wider angle version of the same scene) were presented and participants rated the test image as being the same or different than before on a 6-point scale. We found that both discrimination sensitivity and bias contributed to the boundary extension effect. The discrimination sensitivity difference was at least 28%, and its presence refuted the hypothesis that boundary extension was due solely to participants' response bias to label test pictures as more wide-angled. Instead, our results support the idea that participants' responses reflect false memory beyond the view (i.e., a more wide-angle view of the world). PMID- 27281462 TI - GLT-1-Dependent Disruption of CNS Glutamate Homeostasis and Neuronal Function by the Protozoan Parasite Toxoplasma gondii. AB - The immune privileged nature of the CNS can make it vulnerable to chronic and latent infections. Little is known about the effects of lifelong brain infections, and thus inflammation, on the neurological health of the host. Toxoplasma gondii is a parasite that can infect any mammalian nucleated cell with average worldwide seroprevalence rates of 30%. Infection by Toxoplasma is characterized by the lifelong presence of parasitic cysts within neurons in the brain, requiring a competent immune system to prevent parasite reactivation and encephalitis. In the immunocompetent individual, Toxoplasma infection is largely asymptomatic, however many recent studies suggest a strong correlation with certain neurodegenerative and psychiatric disorders. Here, we demonstrate a significant reduction in the primary astrocytic glutamate transporter, GLT-1, following infection with Toxoplasma. Using microdialysis of the murine frontal cortex over the course of infection, a significant increase in extracellular concentrations of glutamate is observed. Consistent with glutamate dysregulation, analysis of neurons reveal changes in morphology including a reduction in dendritic spines, VGlut1 and NeuN immunoreactivity. Furthermore, behavioral testing and EEG recordings point to significant changes in neuronal output. Finally, these changes in neuronal connectivity are dependent on infection induced downregulation of GLT-1 as treatment with the beta-lactam antibiotic ceftriaxone, rescues extracellular glutamate concentrations, neuronal pathology and function. Altogether, these data demonstrate that following an infection with T. gondii, the delicate regulation of glutamate by astrocytes is disrupted and accounts for a range of deficits observed in chronic infection. PMID- 27281465 TI - Testing the dual-route model of perceived gaze direction: Linear combination of eye and head cues. AB - We have recently proposed a dual-route model of the effect of head orientation on perceived gaze direction (Otsuka, Mareschal, Calder, & Clifford, 2014; Otsuka, Mareschal, & Clifford, 2015), which computes perceived gaze direction as a linear combination of eye orientation and head orientation. By parametrically manipulating eye orientation and head orientation, we tested the adequacy of a linear model to account for the effect of horizontal head orientation on perceived direction of gaze. Here, participants adjusted an on-screen pointer toward the perceived gaze direction in two image conditions: Normal condition and Wollaston condition. Images in the Normal condition included a change in the visible part of the eye along with the change in head orientation, while images in the Wollaston condition were manipulated to have identical eye regions across head orientations. Multiple regression analysis with explanatory variables of eye orientation and head orientation revealed that linear models account for most of the variance both in the Normal condition and in the Wollaston condition. Further, we found no evidence that the model with a nonlinear term explains significantly more variance. Thus, the current study supports the dual-route model that computes the perceived gaze direction as a linear combination of eye orientation and head orientation. PMID- 27281466 TI - An Appraisal of Clinically Meaningful Outcomes Guidelines for Oncology Clinical Trials. PMID- 27281468 TI - Squamous cell carcinoma of the conjunctiva with extraocular involvement: case report and literature review. AB - Squamous cell carcinoma of the conjunctiva is the most frequent malignant tumor of the ocular surface. It is a rare disease with an incidence of 0.13 to 1.9 per 100,000 inhabitants, mainly affecting individuals between 50 and 75 years of age. It tends to have a slow, non-aggressive course. Treatment depends on the extent of the tumor. If there is intraocular involvement, enucleation is indicated, and in the presence of extraocular involvement the orbital exenteration is the standard treatment. We report and discuss the case of an 82 year old male patient having a conjunctival squamous cell carcinoma with intra and extraocular involvement, together with a review of the literature. PMID- 27281467 TI - Oral Health in Pregnancy. AB - Oral health is crucial to overall health. Because of normal physiologic changes, pregnancy is a time of particular vulnerability in terms of oral health. Pregnant women and their providers need more knowledge about the many changes that occur in the oral cavity during pregnancy. In this article we describe the importance of the recognition, prevention, and treatment of oral health problems in pregnant women. We offer educational strategies that integrate interprofessional oral health competencies. PMID- 27281470 TI - [Not Available]. PMID- 27281469 TI - Speciation of Gold Nanoparticles by Ex Situ Extended X-ray Absorption Fine Structure and X-ray Absorption Near Edge Structure. AB - A combined X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) methodology is here presented on a series of partially and fully reduced Au(III) samples. This allows monitoring the relative fraction of Au(III) and Au(0) in the studied samples, displaying a consistent and independent outcome. The strategy followed is based, for the first time, on two structural models that can be fitted simultaneously, and it evaluates the correlation among strongly correlated parameters such as coordination number and the Debye-Waller factor. The results of the present EXAFS and XANES approach can be extended to studies based on X-ray absorption spectroscopy experiments for the in situ monitoring of the formation of gold nanoclusters. PMID- 27281471 TI - Fatigue and Exhaustion in Hypoxia: The Role of Cerebral Oxygenation. AB - Fan, Jui-Lin, and Bengt Kayser. Fatigue and exhaustion in hypoxia: the role of cerebral oxygenation. High Alt Med Biol. 17:72-84, 2016.-It is well established that ascent to high altitude is detrimental to one's aerobic capacity and exercise performance. However, despite more than a century of research on the effects of hypoxia on exercise performance, the underlying mechanisms remain incompletely understood. While the cessation of exercise, or the reduction of its intensity, at exhaustion, implies reduced motor recruitment by the central nervous system, the mechanisms leading up to this muscular derecruitment remain elusive. During exercise in normoxia and moderate hypoxia (~1500-2500 m), peripheral fatigue and activation of muscle afferents probably play a major role in limiting exercise performance. Meanwhile, studies suggested that cerebral tissue deoxygenation may play a pivotal role in impairing aerobic capacity during exercise in more severe hypoxic conditions (~4500-6000 m). However, recent studies using end-tidal CO2 clamping, to improve cerebral tissue oxygenation during exercise in hypoxia, failed to demonstrate an improvement in exercise performance. In light of these recent findings, which seem to contradict the hypothetical role of cerebral tissue deoxygenation as a performance limiting factor at high altitude, this short review aims to provide a critical reappraisal of the extant literature and ends exploring some potential avenues for further research in this field. PMID- 27281472 TI - Increased Cardiometabolic Risk and Worsening Hypoxemia at High Altitude. AB - Miele, Catherine H., Alan R. Schwartz, Robert H. Gilman, Luu Pham, Robert A. Wise, Victor G. Davila-Roman, Jonathan C. Jun, Vsevolod Y. Polotsky, J. Jaime Miranda, Fabiola Leon-Velarde, and William Checkley. Increased cardiometabolic risk and worsening hypoxemia at high altitude. High Alt Med Biol. 17:93-100, 2016.-Metabolic syndrome, insulin resistance, diabetes, and dyslipidemia are associated with an increased risk of cardiovascular disease. While excessive erythrocytosis is associated with cardiovascular complications, it is unclear how worsening hypoxemia of any degree affects cardiometabolic risk factors in high altitude populations. We studied the relationship between daytime resting oxyhemoglobin saturation and cardiometabolic risk factors in adult participants living in Puno, Peru (3825 m above sea level). We used multivariable logistic regression models to study the relationship between having a lower oxyhemoglobin saturation and markers of cardiometabolic risk. Nine hundred and fifty-four participants (mean age 55 years, 52% male) had information available on pulse oximetry and markers of cardiometabolic risk. Average oxyhemoglobin saturation was 90% (interquartile range 88%-92%) and 43 (4.5%) had excessive erythrocytosis. Older age, decreased height-adjusted lung function, and higher body mass index (BMI) were associated with having an oxyhemoglobin saturation <=85%. When adjusting for age, sex, socioeconomic status, having excessive erythrocytosis, and site, we found that each 5% decrease in oxyhemoglobin saturation was associated with a higher adjusted odds of metabolic syndrome (OR = 1.35, 95% CI: 1.07-1.72, p < 0.04), insulin resistance as defined by homeostasis model assessment-insulin resistance (HOMA-IR) >2 mass units (OR = 1.29, 95% CI: 1.00 1.67, p < 0.05), hemoglobin A1c >=6.5% (OR = 1.66, 95% CI: 1.09-2.51, p < 0.04), and high sensitivity C-reactive protein (hs-CRP) >=3 mg/L (OR = 1.46, 95% CI: 1.09-1.96, p < 0.01). In high-altitude populations in Puno, Peru, a higher BMI and lower pulmonary function were associated with lower resting daytime oxyhemoglobin saturation. Lower resting oxyhemoglobin saturation, in turn, was associated with higher odds of having multiple unfavorable cardiometabolic factors. Worsening hypoxia of any degree in high-altitude dwellers may be an independent risk factor for cardiovascular disease. PMID- 27281473 TI - Muscarinic Receptor Activation Affects Pulmonary Artery Contractility in Sheep: The Impact of Maturation and Chronic Hypoxia on Endothelium-Dependent and Endothelium-Independent Function. AB - Giang, Michael, Demosthenes G. Papamatheakis, Dan Nguyen, Ricardo Paez, Carla Blum Johnston, Joon Kim, Alexander Brunnell, Quintin Blood, Ravi Goyal, Lawrence D. Longo, and Sean M. Wilson. Muscarinic receptor activation affects pulmonary artery contractility in sheep: the impact of maturation and chronic hypoxia on endothelium-dependent and endothelium-independent function. High Alt Med Biol. 17:122-132, 2015.-Muscarinic receptor activation in the pulmonary vasculature can cause endothelium-dependent vasodilation and smooth muscle-dependent vasoconstriction. Chronic hypoxia (CH) can modify both of these responses. This study aimed to assess the combined influence of CH and maturation on endothelium dependent and endothelium-independent muscarinic-induced vasoreactivity. This was accomplished by performing wire myography on endothelium-intact or endothelium disrupted pulmonary arterial rings isolated from normoxic or CH fetal and adult sheep. In endothelium-intact arteries, vasodilation was evaluated using cumulative bradykinin doses in phenylephrine and carbachol precontracted pulmonary arterial segments; and vasoconstriction was examined using cumulative doses of carbachol following bradykinin predilation. Effects of nonselective (atropine) and selective M1 (pirenzepine), M2 (AFDX116), and M3 (4-DAMP and Dau5884) muscarinic receptor antagonists were assessed in disrupted arteries. In normoxic arteries, bradykinin relaxation was twofold greater in the adult compared to fetus, while carbachol contraction was fourfold greater. In adult arteries, CH increased bradykinin relaxation and carbachol contraction. In vessels with intact endothelium, maturation and CH augmented maximal response and efficacy for carbachol constriction and bradykinin relaxation. Approximately 50% 80% of adult normoxic and CH endothelium-disrupted arteries contracted to acetylcholine, while ~50% of fetal normoxic and ~10% of CH arteries responded. Atropine reduced carbachol-induced contraction in all vessels. Adult normoxic vessels were most responsive to M3 antagonism, fetal to M2 antagonism, while M1 inhibition had no effect. Overall, muscarinic-induced pulmonary arterial contraction is partially endothelium dependent and appears to develop after birth. Fetuses are more reliant on M3 receptors while M2 receptors predominate in adults, whereas CH augments muscarinic-dependent pulmonary vasoconstriction in both. PMID- 27281474 TI - Tissue responses resulting from tooth movement surgically assisted by corticotomy and corticision in rats. AB - OBJECTIVE: To compare the histological responses in corticotomy- and corticision assisted tooth movement. MATERIALS AND METHODS: Ninety Wistar rats were divided into three groups: C (control-tooth movement only), CT (tooth movement + corticotomy), and CI (tooth movement + corticision). Surgeries were performed on the vestibular and lingual cortical bone of the maxillary first molar. Tooth movement was carried out with nickel-titanium closed coil springs having a force of 30 g. The rats were sacrificed at 3, 14, and 28 days. To evaluate the number of osteoclasts and amount of root resorption, a tartrate-resistant acid phosphatase stain was used. Hematoxylin and eosin staining was performed for areas of hyalinization, and the organic bone matrix was stained with picrosirius. RESULTS: The CT group showed a greater number of osteoclasts than did the C group on day 3 (P < .05). At the same time point, the CT and CI groups showed a delayed onset of organic bone matrix remodeling and a lower incidence of root resorption than did the C group (P < .05). There were also fewer hyalinization areas in the CI group than in the C group on day 3 (P < .05). CONCLUSIONS: Corticotomy effectively increased bone resorption during the early stages of tooth movement, but this increase was not observed for corticision. The surgical procedures did not accelerate organic bone matrix remodeling. Corticotomies and corticisions decreased the risk of root resorption only during the early stages of movement. Corticision reduced the level of hyalinization, while corticotomy did not. PMID- 27281475 TI - Factors associated with hospitalization risk among community living middle aged and older persons: Results from the Swedish Adoption/Twin Study of Aging (SATSA). AB - The aims of the present study were to: (1) describe and compare individual characteristics of hospitalized and not hospitalized community living persons, and (2) to determine factors that are associated with hospitalization risk over time. We conducted a prospective study with a multifactorial approach based on the population-based longitudinal Swedish Adoption/Twin Study of Aging (SATSA). A total of 772 Swedes (mean age at baseline 69.7 years, range 46-103, 59.8% females) answered a postal questionnaire about physical and psychological health, personality and socioeconomic factors. During nine years of follow-up, information on hospitalizations and associated diagnoses were obtained from national registers. Results show that 484 persons (63%) had at least one hospital admission during the follow-up period. The most common causes of admission were cardiovascular diseases (25%) and tumors (22%). Cox proportional hazard regression models controlling for age, sex and dependency within twin pairs, showed that higher age (HR=1.02, p<0.001) and more support from relatives (HR=1.09, p=0.028) were associated with increased risk of hospitalization, while marital status (unmarried (HR=0.75, p=0.033) and widow/widower (HR=0.69, p<0.001)) and support from friends (HR=0.93, p=0.029) were associated with lower risk of hospitalization. Social factors were important for hospitalization risk even when medical factors were controlled for in the analyses. Number of diseases was not a risk in the final regression model. Hospitalization risk was also different for women and men and within different age groups. We believe that these results might be used in future interventions targeting health care utilization. PMID- 27281476 TI - Erratum to: Selection-based instruction and the emergence of topography-based responses to interview questions. AB - [This corrects the article DOI: 10.1007/s40616-014-0013-z.]. PMID- 27281477 TI - Brefeldin A promotes the appearance of oligosaccharyl phosphates derived from Glc3Man9GlcNAc2-PP-dolichol within the endomembrane system of HepG2 cells. AB - We reported an oligosaccharide diphosphodolichol (DLO) diphosphatase (DLODP) that generates dolichyl-phosphate and oligosaccharyl phosphates (OSPs) from DLO in vitro. This enzyme could underlie cytoplasmic OSP generation and promote dolichyl phosphate recycling from truncated endoplasmic reticulum (ER)-generated DLO intermediates. However, during subcellular fractionation, DLODP distribution is closer to that of a Golgi apparatus (GA) marker than those of ER markers. Here, we examined the effect of brefeldin A (BFA), which fuses the GA with the ER on OSP metabolism. In order to increase the steady state level of truncated DLO while allowing formation of mature DLO (Glc3Man9GlcNAc2-PP-dolichol), dolichyl-P mannose Man7GlcNAc2-PP-dolichol mannosyltransferase was partially downregulated in HepG2 cells. We show that BFA provokes GA endomannosidase trimming of Glc3Man9GlcNAc2-PP-dolichol to yield a Man8GlcNAc2-PP-dolichol structure that does not give rise to cytoplasmic Man8GlcNAc2-P. BFA also strikingly increased OSP derived from mature DLO within the endomembrane system without affecting levels of Man7GlcNAc2-PP-dolichol or cytoplasmic Man7GlcNAc2-P. The BFA-provoked increase in endomembrane-situated OSP is sensitive to nocodazole, and BFA causes partial redistribution of DLODP activity from GA- to ER-containing regions of density gradients. These findings are consistent with BFA-provoked microtubule dependent GA-to-ER transport of a previously reported DLODP that acts to generate a novel endomembrane-situated OSP population. PMID- 27281479 TI - Tcf7l2 localization of putative stem/progenitor cells in mouse conjunctiva. AB - Conjunctival integrity and preservation is indispensable for vision. The self renewing capacity of conjunctival cells controls conjunctival homeostasis and regeneration; however, the source of conjunctival self-renewal and the underlying mechanism is currently unclear. Here, we characterize the biochemical phenotype and proliferative potential of conjunctival epithelial cells in adult mouse by detecting proliferation-related signatures and conducting clonal analysis. Further, we show that transcription factor 7-like 2 (T-cell-specific transcription factor 4), a DNA binding protein expressed in multiple types of adult stem cells, is highly correlated with proliferative signatures in basal conjunctival epithelia. Clonal studies demonstrated that Transcription factor 7 like 2 (Tcf7l2) was coexpressed with p63alpha and proliferating cell nuclear antigen (PCNA) in propagative colonies. Furthermore, Tcf7l2 was actively transcribed concurrently with conjunctival epithelial proliferation in vitro. Collectively, we suggest that Tcf7l2 may be involved in maintenance of stem/progenitor cells properties of conjunctival epithelial stem/progenitor cells, and with the fornix as the optimal site to isolate highly proliferative conjunctival epithelial cells in adult mice. PMID- 27281478 TI - VNN1 promotes atherosclerosis progression in apoE-/- mice fed a high-fat/high cholesterol diet. AB - Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE(-/-) mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPARalpha signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE(-/-) mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL cholesterol (119.64%), TNF-alpha (148.74%), interleukin (IL)-1beta (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE(-/-) mice with LV-VNN1. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis. PMID- 27281480 TI - Mitochondrial maintenance via autophagy contributes to functional skeletal muscle regeneration and remodeling. AB - The primary objective of this study was to determine whether alterations in mitochondria affect recovery of skeletal muscle strength and mitochondrial enzyme activity following myotoxic injury. 3-Methyladenine (3-MA) was administered daily (15 mg/kg) to blunt autophagy, and the creatine analog guanidionpropionic acid (beta-GPA) was administered daily (1% in chow) to enhance oxidative capacity. Male C57BL/6 mice were randomly assigned to nontreatment (Con, n = 6), 3-MA treated (n = 6), and beta-GPA-treated (n = 8) groups for 10 wk. Mice were euthanized at 14 days after myotoxic injury for assessment of mitochondrial remodeling during regeneration and its association with the recovery of muscle strength. Expression of several autophagy-related proteins, e.g., phosphorylated Ulk1 (~2- to 4-fold, P < 0.049) was greater in injured than uninjured muscles, indicating a relationship between muscle regeneration/remodeling and autophagy. By 14 days postinjury, recovery of muscle strength (18% less, P = 0.03) and mitochondrial enzyme (e.g., citrate synthase) activity (22% less, P = 0.049) were significantly lower in 3-MA-treated than Con mice, suggesting that the autophagy process plays an important role during muscle regeneration. In contrast, muscle regeneration was nearly complete in beta-GPA-treated mice, i.e., muscle strength recovered to 93% of baseline vs. 78% for Con mice. Remarkably, 14 days allowed sufficient time for a near-complete recovery of mitochondrial function in beta GPA-treated mice (e.g., no difference in citrate synthase activity between injured and uninjured, P = 0.49), indicating a robust mitochondrial remodeling process during muscle regeneration. In conclusion, autophagy is likely activated following muscle injury and appears to play an important role in functional muscle regeneration. PMID- 27281481 TI - Leptin augments recruitment of IRF-1 and CREB to thrombospondin-1 gene promoter in vascular smooth muscle cells in vitro. AB - We previously reported that high pathophysiological concentrations of leptin, the adipocyte-secreted peptide, upregulate the expression of a potent proatherogenic matricellular protein, thrombospondin-1 (TSP-1), in vascular smooth muscle cells. Moreover, this regulation was found to occur at the level of transcription; however, the underlying molecular mechanisms remain unknown. The goal of the present study was to investigate the specific transcriptional mechanisms that mediate upregulation of TSP-1 expression by leptin. Primary human aortic smooth muscle cell cultures were transiently transfected with different TSP-1 gene (THBS1) promoter-linked luciferase reporter constructs, and luciferase activity in response to leptin (100 ng/ml) was assessed. We identified a long THBS1 promoter (-1270/+750) fragment with specific leptin response elements that are required for increased TSP-1 transcription by leptin. Promoter analyses, protein/DNA array and gel shift assays demonstrated activation and association of transcription factors, interferon regulatory factor-1 (IRF-1) and cAMP response element-binding protein (CREB), to the distal fragment of the THBS1 promoter in response to leptin. Supershift, chromatin immunoprecipitation, and coimmunoprecipitation assays revealed formation of a single complex between IRF-1 and CREB in response to leptin; importantly, recruitment of this complex to the THBS1 promoter mediated leptin-induced TSP-1 transcription. Finally, binding sequence decoy oligomer and site-directed mutagenesis revealed that regulatory elements for both IRF-1 (-1019 to -1016) and CREB (-1198 to -1195), specific to the distal THBS1 promoter, were required for leptin-induced TSP-1 transcription. Taken together, these findings demonstrate that leptin promotes a cooperative association between IRF-1 and CREB on the THBS1 promoter driving TSP-1 transcription in vascular smooth muscle cells. PMID- 27281482 TI - Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues. AB - Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K(+) channel inactivation by an unknown site and mechanism. The effects of omega-6 and omega-3 PUFAs were investigated on the heterologously expressed Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation (Kd, 15-43 MUM). C type inactivation was affected by extracellular H(+) and K(+) as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abolished on raising K(+) Replacement of two positively charged residues in the extracellular pore (H508 and K532) abolished the effects of the PUFAs (and extracellular H(+) and K(+)) on C-type inactivation but had no effect on the lipoelectric modulation of voltage sensor activation, suggesting two separable interaction sites/mechanisms of action of PUFAs. Charge calculations suggest that the acidic head group of the PUFAs raises the pKa of H508 and this reduces the K(+) occupancy of the selectivity filter, stabilizing the C-type inactivated state. PMID- 27281483 TI - Clinical Response to Tocilizumab in Severe Thyroid Eye Disease. AB - Tocilizumab, in a preliminary study, was reported to be an effective therapy for moderate to severe thyroid eye disease. The authors describe the clinical response of 2 severe thyroid eye disease cases refractory to intravenous steroids and orbital decompression. Both patients demonstrated improved clinical activity scores with minimal side effects after tocilizumab therapy. In addition, post tocilizumab orbital fat biopsies demonstrated benign adipose tissue without evidence of inflammatory cells. PMID- 27281484 TI - A Concomitant Case of Orbital Granuloma Faciale and Eosinophilic Angiocentric Fibrosis. AB - Granuloma faciale is an eosinophilic dermatosis that typically presents as red brown facial plaques of middle-aged white men, while eosinophilic angiocentric fibrosis is a histologically similar fibrotic condition affecting the respiratory mucosa. Both are very uncommon conditions and pose a therapeutic challenge. While a handful of reports have reported concurrent presentation, the authors present the first case of eyelid granuloma faciale with eosinophlilic angiocentric fibrosis. PMID- 27281485 TI - Vital Signs: Deficiencies in Environmental Control Identified in Outbreaks of Legionnaires' Disease - North America, 2000-2014. AB - BACKGROUND: The number of reported cases of Legionnaires' disease, a severe pneumonia caused by the bacterium Legionella, is increasing in the United States. During 2000-2014, the rate of reported legionellosis cases increased from 0.42 to 1.62 per 100,000 persons; 4% of reported cases were outbreak-associated. Legionella is transmitted through aerosolization of contaminated water. A new industry standard for prevention of Legionella growth and transmission in water systems in buildings was published in 2015. CDC investigated outbreaks of Legionnaires' disease to identify gaps in building water system maintenance and guide prevention efforts. METHODS: Information from summaries of CDC Legionnaires' disease outbreak investigations during 2000-2014 was systematically abstracted, and water system maintenance deficiencies from land-based investigations were categorized as process failures, human errors, equipment failures, or unmanaged external changes. RESULTS: During 2000-2014, CDC participated in 38 field investigations of Legionnaires' disease. Among 27 land based outbreaks, the median number of cases was 10 (range = 3-82) and median outbreak case fatality rate was 7% (range = 0%-80%). Sufficient information to evaluate maintenance deficiencies was available for 23 (85%) investigations. Of these, all had at least one deficiency; 11 (48%) had deficiencies in >=2 categories. Fifteen cases (65%) were linked to process failures, 12 (52%) to human errors, eight (35%) to equipment failures, and eight (35%) to unmanaged external changes. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Multiple common preventable maintenance deficiencies were identified in association with disease outbreaks, highlighting the importance of comprehensive water management programs for water systems in buildings. Properly implemented programs, as described in the new industry standard, could reduce Legionella growth and transmission, preventing Legionnaires' disease outbreaks and reducing disease. PMID- 27281486 TI - Neighborhood context, psychological outlook, and risk behaviors among urban African American youth. AB - OBJECTIVES: Researchers have found a link between neighborhood risk factors and youth risk behaviors. However, the pathways by which this occurs remain poorly understood. This study sought to test a hypothesized pathway that suggests the influence of neighborhood risk on sexual risk and substance use among urban African American youth may operate indirectly via their psychological outlook about current and future opportunities. METHOD: Secondary data analysis using structural equation modeling (SEM) was used to test the conceptual framework. The sample included 592 African American youth (61% female, 39% male) mean age 15.58 years, 1.23 SD. A modified structural equation model (SEM) met prespecified global fit index criteria. RESULTS: The model contained 3 indirect paths linking increased neighborhood risk to increased sexual risk and substance use through higher levels of negative psychological outlook and youth approval of substance use. CONCLUSIONS: These findings increase our understanding of factors that influence the initiation and progression of substance use and sexual risk behaviors among urban African American adolescents. (PsycINFO Database Record PMID- 27281487 TI - Family dynamics and aggressive behavior in Latino adolescents. AB - OBJECTIVES: Despite high prevalence rates and evidence that acculturation is associated with adolescent behavioral and mental health in Latino youth, little research has focused on aggressive behavior for this population. The aim of the current study was to fill this research gap by examining the influence of several aspects of family functioning, including parent-adolescent conflict, parent worry, and parent marital adjustment, on aggression among Latino adolescents. METHOD: Data come from the Latino Acculturation and Health Project (LAHP), a longitudinal investigation of acculturation in Latino families in North Carolina and Arizona. Hierarchical linear modeling was used to estimate a longitudinal rater effects model of adolescent aggression as reported by 258 Latino adolescents each paired with 1 parent for a total of 516 participants across 4 time points over a span of 18 months. RESULTS: Results indicated a general decline in aggression over the study window. In addition, parent-adolescent conflict and parent worry predicted higher adolescent aggression whereas parent marital adjustment predicted lower adolescent aggression. CONCLUSIONS: The salience of family risk factors for aggression among Latino adolescents is discussed. (PsycINFO Database Record PMID- 27281489 TI - Body Composition, Neuromuscular Performance, and Mobility: Comparison Between Regularly Exercising and Inactive Older Women. AB - The purpose of this study was to evaluate the differences in body composition, neuromuscular performance, and mobility in healthy, regularly exercising and inactive older women, and examine the relationship between skeletal muscle indices and mobility. Overall, 32 healthy older women participated. They were divided into groups according to their physical activity history as regularly exercising (n = 22) and inactive (n = 10) women. Body composition, hand grip strength, leg extensor muscle strength, rapid force development, power output, and mobility indices were assessed. Regularly exercising women had lower fat mass and higher values for leg extensor muscle strength and muscle quality, and also for mobility. Leg extensor muscle strength and power output during vertical jumping and appendicular lean mass per unit of body mass were associated with mobility in healthy older women. It was concluded that long-term regular exercising may have beneficial effects on body composition and physical function in older women. PMID- 27281488 TI - Thermosensitive and Highly Flexible Hydrogels Capable of Stimulating Cardiac Differentiation of Cardiosphere-Derived Cells under Static and Dynamic Mechanical Training Conditions. AB - Cardiac stem cell therapy has been considered as a promising strategy for heart tissue regeneration. Yet achieving cardiac differentiation after stem cell transplantation remains challenging. This compromises the efficacy of current stem cell therapy. Delivery of cells using matrices that stimulate the cardiac differentiation may improve the degree of cardiac differentiation in the heart tissue. In this report, we investigated whether elastic modulus of highly flexible poly(N-isopropylamide) (PNIPAAm)-based hydrogels can be modulated to stimulate the encapsulated cardiosphere derived cells (CDCs) to differentiate into cardiac lineage under static condition and dynamic stretching that mimics the heart beating condition. We have developed hydrogels whose moduli do not change under both dynamic stretching and static conditions for 14 days. The hydrogels had the same chemical structure but different elastic moduli (11, 21, and 40 kPa). CDCs were encapsulated into these hydrogels and cultured under either native heart-mimicking dynamic stretching environment (12% strain and 1 Hz frequency) or static culture condition. CDCs were able to grow in all three hydrogels. The greatest growth was found in the hydrogel with elastic modulus of 40 kPa. The dynamic stretching condition stimulated CDC growth. The CDCs demonstrated elastic modulus-dependent cardiac differentiation under both static and dynamic stretching conditions as evidenced by gene and protein expressions of cardiac markers such as MYH6, CACNA1c, cTnI, and Connexin 43. The highest differentiation was found in the 40 kPa hydrogel. These results suggest that delivery of CDCs with the 40 kPa hydrogel may enhance cardiac differentiation in the infarct hearts. PMID- 27281490 TI - Simvastatin and oxidative stress in humans: A randomized, double-blinded, placebo controlled clinical trial. AB - Simvastatin reduces the blood concentration of cholesterol by inhibiting hydroxymethylglutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, and thereby reduces the risk of cardiovascular disease. In addition, simvastatin treatment leads to a reduction in fluxes in mitochondrial respiratory complexes I and II and might thereby reduce the formation of reactive oxygen species, which have been implicated in the pathogenesis of arteriosclerosis. Therefore, we hypothesized that simvastatin may reduce oxidative stress in humans in vivo. We conducted a randomized, double-blinded, placebo-controlled study in which subjects were treated with either 40mg of simvastatin or placebo for 14 days. The endpoints were six biomarkers for oxidative stress, which represent intracellular oxidative stress to nucleic acids, lipid peroxidation and plasma antioxidants, that were measured in urine and plasma samples. A total of 40 participants were included, of which 39 completed the trial. The observed differences between simvastatin and placebo groups in the primary outcomes, DNA and RNA oxidation, were small and nonsignificant (p=0.68), specifically, 3% in the simvastatin group compared to 7.1% in the placebo group for DNA oxidation and 7.3% in the simvastatin group compared to 3.4% in the placebo group. The differences in biomarkers related to plasma were not statistically significant between the treatments groups, with the exception of total vitamin E levels, which, as expected, were reduced in parallel with the reduction in plasma cholesterol. In healthy young male volunteers, short term simvastatin treatment, which considerably reduces cholesterol, does not lead to a clinically relevant reduction in a panel of measures of oxidative stress. Whether simvastatin has effects on oxidative stress in diseased populations, such as diabetes or hemochromatosis, where oxidative stress is prominent, is unknown but seems unlikely. PMID- 27281491 TI - N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes. AB - Oxidative stress plays critical roles in the pathogenesis of diabetes, hypertension, and atherosclerosis; some authors reported that fat accumulation correlates to systemic oxidative stress in human and mice, but cellular redox environment effect on lipid accumulation is still unclear. In our laboratory we used mouse embryonic fibroblasts (undifferentiated cells: CC), which are capable of differentiating into mature adipocytes (differentiated cells: DC) and accumulate lipids, as obesity model. Here we analyzed the role of the well-known antioxidant and glutathione precursor N-acetylcysteine (NAC) in cellular MAPK modulation and lipid accumulation. We evaluated the effect of NAC on the adipogenic differentiation pathway using different doses: 0.01, 0.1, 1 and 5mM; no toxic doses in these cells. A dose of 5mM NAC [DCN-5] provoked a significant decrease in triglyceride accumulation (72+/-10 [DCN-5] vs 169+/-15 [DC], p<0.01), as well in Oil Red O stained neutral lipid content (120+/-2 [DCN-5] vs 139+/-12 [DC], p<0.01). Molecular mechanisms responsible for adipogenic differentiation involve increase of the expression of phosphoERK1/2 and phosphoJNK, 5mM NAC treatment inhibited both pERK1/2 and pJNK protein levels. We also evaluated the mitotic clonal expansion (MCE) which takes place during adipogenesis and observed an increase in DC at a rate of 1.5 cells number compared to CC at day 2, whereas the highest doses of NAC significantly inhibited MCE. Our results suggest that NAC inhibits lipid accumulation and the MAPK phosphorylation in mouse embryonic fibroblasts during adipogenic differentiation and further contribute to probe the importance of cellular redox environment in adipogenesis. PMID- 27281492 TI - Unexplained Homonymous Hemianopia. PMID- 27281493 TI - Perceptions of "Natural" and "Additive-Free" Cigarettes and Intentions to Purchase. AB - In August 2015, the Food and Drug Administration (FDA) issued warning letters to cigarette manufacturers promoting brands as "natural" or "additive-free" because of concerns that such marketing claims might mislead consumers into believing that these brands are less dangerous to smoke than others. The current study examined consumer beliefs about the relative harms of "natural" cigarettes, and whether these beliefs influenced perceptions of advertising and purchase intentions when participants were shown an advertisement for American Spirit cigarettes. Data were collected using a web-based survey conducted in 2013 among 3,006 U.S.-based web panel members aged 15 to 65 years. Ratings of "natural" cigarette health risks (i.e., misperceptions) differed by sex, race, education, smoking status, and age. Controlling for perceived risks of other cigarette types, never smokers ( B = -0.31, p < .001) and ever/former smokers ( B = -0.15, p = .002) had significantly fewer misperceptions of "natural" cigarettes than current smokers. Current smoking (odds ratio [OR] = 17.8), believing the ad was truthful (OR = 1.18), and having more misperceptions about "natural" cigarette health risks (OR = 1.13) were independently associated with greater purchase intention. Consumers perceived cigarettes marketed as "natural" or "additive free" as less harmful, and this influenced their perceptions of advertising claims and intention to purchase, controlling for other factors. These findings underscore Food and Drug Administration's recent warning letters. PMID- 27281495 TI - Reducing Mediastinitis after Sternotomy with Combined Chlorhexidine-Isopropyl Alcohol Skin Disinfection: Analysis of 3,000 Patients. AB - BACKGROUND: Reducing surgical site infections (SSI) following median sternotomy remains a challenge for cardiac surgeons. Standard prophylaxis of SSI at our institution includes pre-operative skin disinfection with isopropyl alcohol (IPA). The addition of chlorhexidine gluconate (CHG) has the theoretical advantage of longer antimicrobial activity (>48h), compared with 2 h for IPA alone. OBJECTIVES: This prospective registry study was conducted to evaluate the effect of combined CHG-IPA (ChloraPrep(r)) skin antiseptic on the incidence of sternal surgical incision infections after cardiac surgical procedures via median sternotomy. METHODS: Between September 2011 and November 2013, 3,942 consecutive patients underwent cardiac surgery with median sternotomy at our institution. Among them, 2,985 patients met inclusion criteria and were enrolled in the study. The complete cohort was prospectively divided into two registries. In registry 1 (1,523 patients), CHG-IPA was used to disinfect skin at the thoracic operative site prior to incision. In registry 2 (1,462 patients), single IPA disinfection was used. The primary endpoint was the incidence of post-sternotomy mediastinitis within 30 d of surgery. Secondary endpoints were SSI of any other kind, 30-d survival, and hospital length of stay. RESULTS: Both registries were well matched in baseline characteristics and main risk factors. Post-operative data analysis revealed reduction in the rate of post-sternotomy mediastinitis in registry 1 (29 patients, 1.9%) versus registry 2 (62 patients, 4.2%), p = 0.0002. No relevant difference in incidence of other surgical site infections, length of hospital stay, and 30-d mortality was found. CONCLUSIONS: Skin disinfection with combined chlorhexidine-isopropyl alcohol reduced the incidence of mediastinitis in elective adult cardiac surgery with median sternotomy but did not affect other types of surgical site infections. PMID- 27281494 TI - Cyclic nucleotide signaling is required during synaptic refinement at the Drosophila neuromuscular junction. AB - The removal of miswired synapses is a fundamental prerequisite for normal circuit development, leading to clinical problems when aberrant. However, the underlying activity-dependent molecular mechanisms involved in synaptic pruning remain incompletely resolved. Here the dynamic properties of intracellular calcium oscillations and a role for cAMP signaling during synaptic refinement in intact Drosophila embryos were examined using optogenetic tools. We provide In vivo evidence at the single gene level that the calcium-dependent adenylyl cyclase rutabaga, the phosphodiesterase dunce, the kinase PKA, and Protein Phosphatase 1 (PP1) all operate within a functional signaling pathway to modulate Sema2a dependent chemorepulsion. It was found that presynaptic cAMP levels were required to be dynamically maintained at an optimal level to suppress connectivity defects. It was also proposed that PP1 may serve as a molecular link between cAMP signaling and CaMKII in the pathway underlying refinement. The results introduced an in vivo model where presynaptic cAMP levels, downstream of electrical activity and calcium influx, act via PKA and PP1 to modulate the neuron's response to chemorepulsion involved in the withdrawal of off-target synaptic contacts. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 39-60, 2017. PMID- 27281496 TI - First-line chemotherapy in low-risk gestational trophoblastic neoplasia. AB - BACKGROUND: This is the second update of a Cochrane review that was first published in 2009, Issue 1, . Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear. OBJECTIVES: To determine the efficacy and safety of first line chemotherapy in the treatment of low-risk GTN. SEARCH METHODS: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase in September 2008, February 2012, and January 2016. In addition, we searched online trial registers for protocols and ongoing trials. SELECTION CRITERIA: For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated versions of the review, we included only RCTs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed using the random-effects model. MAIN RESULTS: We included seven RCTs (667 women) in this updated review. Most studies were at a low or moderate risk of bias and all compared methotrexate with actinomycin D. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) actinomycin D (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV actinomycin D (75 women), one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV actinomycin D (49 women), and one study compared eight-day IM MTX-FA with bi weekly pulsed IV actinomycin D. One study contributed no data. Moderate-certainty evidence indicates that actinomycin D is probably more likely to lead to primary cure than methotrexate (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.57 to 0.75; six trials, 577 participants; I(2) = 26%), and first-line methotrexate treatment is probably more likely to fail than actinomycin D treatment (RR 3.55, 95% CI 1.81 to 6.95; six trials, 577 participants; I(2) = 61%; moderate-certainty evidence) Low-certainty evidence suggests that there may be little or no difference between methotrexate and actinomycin D treatment with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too inconsistent to be conclusive. Low-certainty evidence suggests that there may be little or no difference in the risk of severe adverse events (SAEs) between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I2 = 60%); however, the direction of effect favours methotrexate and more evidence is needed. Furthermore, evidence from subgroup analyses suggests that actinomycin D may be associated with a greater risk of SAEs than methotrexate (low-certainty evidence). We found no evidence on the effect of these treatments on future fertility. AUTHORS' CONCLUSIONS: Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN. PMID- 27281497 TI - Atomic Details of the Interactions of Glycosaminoglycans with Amyloid-beta Fibrils. AB - The amyloid plaques associated with Alzheimer's disease (AD) comprise fibrillar amyloid-beta (Abeta) peptides as well as non-protein factors including glycosaminoglycan (GAG) polysaccharides. GAGs affect the kinetics and pathway of Abeta self-assembly and can impede fibril clearance; thus, they may be accessory molecules in AD. Here we report the first high-resolution details of GAG-Abeta fibril interactions from the perspective of the saccharide. Binding analysis indicated that the GAG proxy heparin has a remarkably high affinity for Abeta fibrils with 3-fold cross-sectional symmetry (3Q). Chemical synthesis of a uniformly (13)C-labeled octasaccharide heparin analogue enabled magic-angle spinning solid-state NMR of the GAG bound to 3Q fibrils, and measurements of dynamics revealed a tight complex in which all saccharide residues are restrained without undergoing substantial conformational changes. Intramolecular (13)C-(15)N dipolar dephasing is consistent with close (<5 A) contact between GAG anomeric position(s) and one or more histidine residues in the fibrils. These data provide a detailed model for the interaction between 3Q-seeded Abeta40 fibrils and a major non-protein component of AD plaques, and they reveal that GAG-amyloid interactions display a range of affinities that critically depend on the precise details of the fibril architecture. PMID- 27281498 TI - Effects of maternal depression on family food insecurity. AB - We use data from the Early Childhood Longitudinal Study-Birth Cohort to estimate the effects of maternal depression, a condition that is fairly common and can be severe, on food insecurity, a hardship that has increased substantially in the U.S. Using various model specifications, we find convincing evidence that severe maternal depression increases the likelihood that young children experience food insecurity by 23-79%, with estimates depending on model specification and measures of depression and food insecurity. For household food insecurity, the corresponding estimates are 11-69%. We also find that maternal depression increases reliance on several types of public programs, suggesting that the programs play a buffering role. PMID- 27281499 TI - SURGERY VERSUS ENDOSCOPIC THERAPIES FOR EARLY CANCER AND HIGH-GRADE DYSPLASIA IN THE ESOPHAGUS: a systematic review. AB - BACKGROUND: Esophageal cancer occurs as a local disease in 22% of cases, and a minority of this disease is limited to the mucosa or submucosa (early lesions). Endoscopic mucosal resection, endoscopic submucosal dissection, photodynamic therapy, laser therapy, and argon plasma coagulation have emerged as alternatives to surgical resection for early lesions. OBJECTIVE: The aim of this systematic review is to identify studies that statistically compare survival, disease-free survival, morbidity and mortality associated with the procedure, and mortality associated with cancer in the endoscopic versus surgical therapies. DATA SOURCES: A systematic review using MEDLINE, COCHRANE, EMBASE, EBSCO, LILACS, Library University of Sao Paulo, BVS, and SCOPE. STUDY SELECTION: Randomized controlled trial, controlled clinical trial, clinical trial, and cohort study. CRITERIA: - Studies that statistically compare survival, disease-free survival, morbidity and mortality associated with the procedure, and mortality associated with cancer in patients who underwent endoscopic and surgical therapy for early lesions of esophageal cancer. DATA EXTRACTION: Independent extraction of the articles by two authors using predefined data fields, including study quality indicators. LIMITATION: Only retrosprospective cohort studies comparing the endoscopic and surgical therapies were recovered. RESULTS: The survival rates after 3 and 5 years were different and exhibited superiority with the surgical therapies over time. Endoscopy is superior in the control of mortality related to cancer with a high rate of disease recurrence. With regard to the comorbidity and the mortality associated with the procedure, endoscopy is superior. CONCLUSION: There is no evidence from clinical trials. In this systematic review, surgical therapies showed superiority for survival, and endoscopic therapies showed superiority in the control of mortality related to cancer with a high rate of disease recurrence; also, for the comorbidity and the mortality associated with the procedure, endoscopy is superior. Prospective, controlled trials with large sample sizes are necessary to confirm the results of the current analysis. PMID- 27281500 TI - DEPRESSIVE EPISODE INCIDENCE IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH PEGYLATED INTERFERON AND RIBAVIRIN. AB - BACKGROUND: The effectiveness of antiviral therapy with pegylated interferon and ribavirin for chronic hepatitis C is far from ideal and presents several adverse events. Among such events, there is the depressive episode that can even lead to treatment discontinuity. OBJECTIVE: Analyze the incidence of depressive episodes in patients with chronic hepatitis C treated with pegylated interferon (IFN-PEG) and ribavirin, as well as the possible factors associated with its occurrence and its impact on patients' sustained virological response. METHODS: People with chronic hepatitis C undergoing antiviral therapy were interviewed at the baseline, at the 4th, 12th, 24th and 48th treatment weeks and 4 weeks after the end of it, using the HADS scale for tracking the depressive episode. Patients with HADS >=9 were subjected to Beck Depression Inventory (BDI-II) to grade the episode. Clinical, sociodemographic, laboratorial and histological variables were obtained to identify factors related to the onset of depression. The sustained virological response rate (negative HCV-RNA 6 months after end of therapy) was compared among patients with and without depressive symptoms. RESULTS: The study comprised 32 patients, most men (59%) with mean age of 54+/-11.13 years old. Genotype non-1 was prevalent (56%) and 81% of the patients were non-cirrhotic. The depressive episode was diagnosed in 25% of the patients and the peak incidence was found in the 12th treatment week. The depressive episode was moderate in 87% of the patients and only one patient abandoned the treatment. None of the analyzed factors was associated with depressive episode onset. A trend was observed in female patients ( P =0.08). The sustained virological response rate was of 75% and 67% in patients with and without depressive episode, respectively ( P =0.66). CONCLUSION: The incidence of depressive episodes in patients with chronic hepatitis C undergoing antiviral therapy was of 25% and the 12th treatment week was the most critical one. The presence of depressive episode did not affect the sustained virological response rate. PMID- 27281501 TI - DEPRESSION AND ANXIETY IN PARENTS OF CHILDREN WHO ARE CANDIDATES FOR LIVER TRANSPLANTATION. AB - BACKGROUND: The primary stress factor for families in the pre-transplant period is reported as the waiting time for suitable organs, leading to anxiety, despair, and distress. OBJECTIVE: We investigated the psychosocial factors, anxiety and depression, in the parents of children who are candidates for liver transplantation. METHODS: Thirty-five pediatric liver transplantation candidates and their 38 parents, from February to August 2014, were included. Participants were evaluated using the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression Scale (CGI). RESULTS: We found that a significant number of parents (n=25, 65.7%) were diagnosed with clinical psychiatric disease: 18.4% (n=7) with depression and 47.3% (n=18) with anxiety disorders. There was a significant difference in the examination scores of parents between genders (P <0.05). There was also a significant difference in CGI and HAM-D scores of parents relative to the history and presence of liver disease (P <0.05). CONCLUSION: The rate of these disorders was high in relation to the prevalence of depression and anxiety disorders in the community reported in the literature. Therefore, it is necessary to evaluate psychosocial factors of parents of all transplant candidate children as a part of routine care so that the high-risk to family members and to enable early intervention. PMID- 27281502 TI - REDUCED HAND GRIP STRENGTH IN OVERWEIGHT AND OBESE CHRONIC HEPATITIS C PATIENTS. AB - BACKGROUND: Hepatitis C is a liver disease that causes significant changes in metabolism, and also has an impact on nutritional status. OBJECTIVE: To evaluate the nutritional status and cardiovascular risk in patients with chronic hepatitis C. METHODS: This cross-sectional study investigated 58 patients with chronic hepatitis C, non-cirrhotic and were not under active pharmacological treatment. Patients with significant alcohol consumption (greater than 10 g ethanol/day) were excluded. Patients underwent nutritional assessment through anthropometric measurements and functional assessment using hand grip strength by dynamometry. The physical activity was assessed using the International Physical Activity Questionnaire. Patients also underwent clinical and laboratory evaluation. Cardiovascular risk was calculated by the Framingham score. RESULTS: The mean age of patients was 51.6+/-9.7 years, 55.2% were female, and 79.3% had genotype 1. The most prevalent degree of fibrosis was F1 (37.9%) followed by F2 (27.6%) and F3 (1.7%). The prevalence of overweight/obesity considering the body mass index was 70.7%. However, 57.7% of men and 68.8% of women were considered malnourished according to hand grip strength. These patients also had waist circumference (93.5+/-10.7 cm) and neck circumference (37.0+/-3.6 cm) high. Almost 60% of patients were considered sedentary or irregularly active. In relation to cardiovascular risk, 50% of patients had high risk of suffering a cardiovascular event within 10 years. CONCLUSION: Although most patients with hepatitis C presented overweight, associated with high cardiovascular risk, they also have reduced functional capacity, indicative of protein-caloric commitment. Therefore, body mass index can not be considered the only method of assessment for nutritional diagnosis of patients with liver disease. Adopting methods such as hand grip strength can be important for a better understanding of nutritional status of these patients. PMID- 27281503 TI - ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues. AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. OBJECTIVE: The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. METHODS: Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. RESULTS: Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. CONCLUSION: The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions. PMID- 27281504 TI - ESOPHAGEAL CARCINOMA: IS SQUAMOUS CELL CARCINOMA DIFFERENT DISEASE COMPARED TO ADENOCARCINOMA? A transversal study in a quaternary high volume hospital in Brazil. AB - BACKGROUND: Esophageal cancer is one of the leading causes of mortality among the neoplasms that affect the gastrointestinal tract. There are several factors that contribute for development of an epidemiological esophageal cancer profile in a population. OBJECTIVE: This study aims to describe both clinically and epidemiologically the population of patients with diagnosis of esophageal cancer treated in a quaternary attention institute for cancer from January, 2009 to December, 2011, in Sao Paulo, Brazil. METHODS: The charts of all patients diagnosed with esophageal cancer from January, 2009, to December, 2011, in a Sao Paulo (Brazil) quaternary oncology institute were retrospectively reviewed. RESULTS: Squamous cell cancer made up to 80% of the cases of esophageal cancer. Average age at diagnosis was 60.66 years old for esophageal adenocarcinoma and 62 for squamous cell cancer, average time from the beginning of symptoms to the diagnosis was 3.52 months for esophageal adenocarcinoma and 4.2 months for squamous cell cancer. Average time for initiating treatment when esophageal cancer is diagnosed was 4 months for esophageal adenocarcinoma and 4.42 months for squamous cell cancer. There was a clear association between squamous cell cancer and head and neck cancers, as well as certain habits, such as smoking and alcoholism, while adenocarcinoma cancer showed more association with gastric cancer and gastroesophageal reflux disease. Tumoral bleeding and pneumonia were the main causes of death. No difference in survival rate was noted between the two groups. CONCLUSION: Adenocarcinoma and squamous cell carcinoma are different diseases, but both are diagnosed in advanced stages in Brazil, compromising the patients' possibilities of cure. PMID- 27281505 TI - LACK OF ASSOCIATION BETWEEN HELICOBACTER PYLORI'S VIRULENCE AND INCREASED SERUM C REACTIVE PROTEIN LEVELS IN FUNCTIONAL DYSPEPTIC PATIENTS. AB - BACKGROUND: Recently, a great variety of studies aimed to investigate and even suggest Helicobacter pylori as an important key factor in gastrointestinal and non-gastrointestinal events development. The well-established relationship between bacterial virulence and increased risk for peptic ulcer or gastric carcinoma is not so clear when comparing inflammation markers alterations, such C reactive protein, with the pathogen. OBJECTIVE: The objective of this study was to evaluate the presence of H. pylori, bacterial virulence and C-reactive protein serum levels in individuals diagnosed with functional dyspepsia. METHODS: Were prospectively included in this study 489 dyspeptic individuals. They fulfill Rome III clinical criteria for the diagnosis of functional dyspepsia with no organic disease at endoscopy. The bacterial infection was established by histology and urease rapid test. The levels of serum C-reactive protein were obtained by immunonefelometry and CagA status of H. pylori positive individuals was determined through an imunoenzimatic assay. RESULTS: Prevalence rate of H. pylori was 66.3% and virulence factor CagA was detected in nearly 43% of positive samples. In addition, it has been noticed an association between Ilex paraguariensis (yerba mate) consumption and pathogen's prevalence. An important effect of bacterial infection on inflammation was only observed in gastric epithelium. CONCLUSION: No systemic response to the pathogen, measured through C reactive protein levels, was observed, regardless of CagA status. Otherwise, the intake of yerba mate should be considered as a cultural factor possibly related to H. pylori's transmission. PMID- 27281506 TI - H. PYLORI INFECTION, ENDOSCOPIC, HISTOLOGICAL ASPECTS AND CELL PROLIFERATION IN THE GASTRIC MUCOSA OF PATIENTS SUBMITTED TO ROUX-EN-Y GASTRIC BYPASS WITH CONTENTION RING: a cross sectional endoscopic and immunohistochemical study. AB - BACKGROUND: Morbid obesity treatment through vertical gastroplasty Roux-en-Y gastric bypass initially used a contention ring. However, this technique may create conditions to the development of potentially malign alterations in the gastric mucosa. Although effective and previously performed in large scale, this technique needs to be better evaluated in long-term studies regarding alterations caused in the gastric mucosa. OBJECTIVE: To analyze the preoperative and postoperative endoscopic, histological and cell proliferation findings in the gastric antrum and body mucosa of patients submitted to the Roux-en-Y gastric bypass with a contention ring. METHODS: We retrospectively evaluated all patients submitted to Roux-en-Y gastric bypass with a contention ring with more than 60 months of postoperative follow-up. We compared the preoperative (gastric antrum and body) and postoperative (gastric pouch) gastric mucosa endoscopic findings, cell proliferation index and H. pylori prevalence. We evaluated cell proliferation through Ki-67 antibody immunohistochemical expression. RESULTS: In the study period, 33 patients were operated with the Roux-en-Y gastric bypass using a contention ring. We found a chronic gastritis rate of 69.7% in the preoperative period (gastric antrum and body) and 84.8% in the postoperative (gastric pouch). H. pylori was present in 18.2% of patients in the preoperative period (gastric antrum and body) and in 57.5% in the postoperative (gastric pouch). Preoperative cell proliferation index was 18.1% in the gastric antrum and 16.2% in the gastric body, and 23.8% in the postoperative gastric pouch. The postoperative cell proliferation index in the gastric pouch was significantly higher (P=0.001) than in the preoperative gastric antrum and body. Higher cell proliferation index and chronic gastritis intensity were significantly associated to H. pylori presence (P=0.001 and P=0.02, respectively). CONCLUSION: After Roux en-Y gastric bypass with contention ring, there was a higher chronic gastritis incidence and higher cell proliferation index in the gastric pouch than in the preoperative gastric antrum and body. Mucosa inflammation intensity and cell proliferation index in the postoperative gastric pouch were associated to H. pylori presence and were higher than those found in the preoperative gastric antrum and body mucosa. PMID- 27281507 TI - Burden of disease and increasing prevalence of inflammatory bowel disease in a population-based cohort in the Netherlands. AB - BACKGROUND: Reported epidemiology and phenotype distributions vary widely and disease burden of inflammatory bowel disease (IBD) is poorly described. Our aim was to establish these features in a population-based cohort covering 319 976 inhabitants. Furthermore, differences between tertiary referral and peripheral hospital patients were quantified. METHODS: IBD patients in the adherence area of three peripheral hospitals (2004-2012) were included. Medical and surgical treatment data were obtained. Quality of life and disease activity were evaluated. An outpatient cohort from a tertiary referral centre was accrued. RESULTS: A total of 1461 patients were included: 761 (52.1%) with ulcerative colitis (UC), 579 (39.5%) with Crohn's disease (CD) and 121 (8.3%) with IBD unspecified. Point prevalence of IBD was 432.1 per 100 000 inhabitants in 2010, which increased significantly over time, P-value of less than 0.0001. The mean annual incidence was 17.2 for UC, 10.5 for CD and 2.2 for IBD-unspecified. Tertiary referral Crohn's patients used thiopurines and biological therapy and underwent surgery significantly more often than patients in peripheral hospitals (P<0.0001). Disease activity correlated negatively with quality of life (P<0.0001) in UC and CD. CONCLUSION: The prevalence of IBD is still increasing. Burden of disease was significantly more severe, mainly in Crohn's patients, in the referral centre, highlighting the importance of population-based studies to accurately describe phenotype distribution and disease burden. PMID- 27281508 TI - Spin-Free [2]R12 Basis Set Incompleteness Correction to the Local Multireference Configuration Interaction and the Local Multireference Average Coupled Pair Functional Methods. AB - The local multireference configuration interaction (LMRCI) and local multireference averaged coupled pair functional (LMRACPF) methods are extended to include explicit correlation via the universal spin-free [2]R12 basis set incompleteness correction. Four test cases are examined to measure the performance of the LMRCI+[2]R12 (without and with the Davidson + Q correction for size-extensivity) and LMRACPF+[2]R12 methods. These tests examine bond dissociation energies (BDEs) for ethene, perfluoroethene, propene, and 2-butene. As has been demonstrated for other methods, the LMRCI+[2]R12/LMRCI+Q+[2]R12/LMRACPF+[2]R12 BDEs are as accurate as the conventional LMRCI/LMRACPF BDEs that are computed with the basis set one cardinal number higher. It is shown that LMRCI+[2]R12/LMRCI+Q+[2]R12/LMRACPF+[2]R12 BDEs computed with the June calendar basis sets preserve the accuracy of the corresponding BDEs computed with the conventional aug-cc-pVXZ basis sets (where X = D, T, Q). PMID- 27281511 TI - Toward Leiodermatolide: Synthesis of the Core Structure. AB - The macrocyclic core (35) of the marine natural product leiodermatolide (1) was synthesized from two key fragments, vinyl iodide 23 (C1-C11 part) and vinyl stannane 31 (C12-C18 part). A Stille coupling led to conjugated Z,Z-diene 32. The derived seco acid 34 was cyclized using a Yamaguchi macrolactonization. Key steps in the assembly of vinyl iodide 23 were a Paterson aldol reaction, and a Kumada coupling on a triflate derivative to create the C4-C5 trisubstituted double bond. The two stereocenters in fragment 31 were established by a Marshall-Tamaru reaction. The longest linear sequence comprises 20 steps. PMID- 27281509 TI - Monoclonal antibody-based optical molecular imaging probes; considerations and caveats in chemistry, biology and pharmacology. AB - The monoclonal antibody (mAb) has proven to be a good platform for designing specific molecular imaging probes due to its superior binding specificity. Several optical imaging probes have been developed for surgical navigation in patients and are in early phase clinical trials. However, an inherent limitation of using the mAb is its pharmacokinetics which result in a prolonged circulating half-life and slow clearance from the body. This results in undesirable target to background ratios during imaging. In this review, we first describe the mAb as a platform material for optical probe design and then discuss optimizing the design of monoclonal antibody-based optical molecular imaging probes by focusing on chemistry, biology and pharmacology. PMID- 27281510 TI - Intracellular and in vivo oxygen sensing using phosphorescent iridium(III) complexes. AB - Molecular oxygen plays an indispensable role as a terminal electron acceptor in the electron transport chain in mitochondria. Acute or chronic oxygen deprivation (hypoxia) in organisms results in various diseases, and the elucidation of the pathogenic mechanism of hypoxia-related diseases and various cellular responses to hypoxia is an urgent issue. Optical oxygen imaging methods using phosphorescent probes have opened up techniques for noninvasive imaging of the intracellular and tissue oxygen status, and oxygen-sensitive probes play a key role in the development of this approach. We expect that phosphorescent Ir(III) complexes can serve as new oxygen-sensing probes for intracellular and intravascular oxygen imaging in vivo. PMID- 27281513 TI - Three-dimensional transvaginal sonographic assessment of uterine volume as preoperative predictor of need to morcellate in women undergoing laparoscopic hysterectomy. AB - OBJECTIVE: In light of recent statements from the United States Food and Drug Administration warning against the use of power morcellation of uterine leiomyomas during laparoscopy, we sought to evaluate the use of preoperative two- (2D) and three- (3D) dimensional transvaginal ultrasound (US) assessment of uterine volume to predict the need for morcellation in women undergoing laparoscopic hysterectomy (LH). METHODS: This was a prospective observational study performed between October 2008 and November 2011 in a tertiary referral laparoscopic unit. All women scheduled to undergo LH were included and underwent detailed preoperative transvaginal US. Uterine volumes were calculated using 2D US measurements (ellipsoid formula), and using Virtual Organ Computer-aided AnaLysis (VOCALTM) having acquired 3D-US volumes of the uterus. Age, parity, need to morcellate and final uterine dry weight at histology were recorded. The estimated uterine volumes were then incorporated into a previously published logistic regression model to predict the need to morcellate for both nulliparous and parous women. The probability threshold cut-off of 0.14 (95% sensitivity) was evaluated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratios (LRs). The performance of the models incorporating 2D- and 3D-US calculations were compared with 2D- and 3D US-generated volumes alone, using receiver-operating characteristics (ROC) curves. RESULTS: Of 76 women who underwent LH during the study period, 79% (n = 60) had complete background and 3D-US data. Their mean age was 43.7 years, 91.7% were parous and 35% underwent morcellation. The greatest uterine volume that did not require morcellation was 404 mL estimated using 3D-US, which corresponded to a uterine volume of 688.8 mL using 2D-US. The smallest uterine volume that required morcellation was 118.9 mL using 3D-US, which corresponded to a uterine volume of 123.4 mL using 2D-US. The 3D-US uterine volume for parous women with a sensitivity of 95% based on ROC-curve analysis was approximately 120 mL, which equated to a predicted probability of morcellation cut-off of 0.14. For this cut off, specificity was 55.00%, PPV was 51.35%, NPV was 95.65%, LR+ was 2.11 and LR- was 0.09. Areas under the ROC curves for the morcellation logistic regression model were 0.769 (95% CI, 0.653-0.886) and 0.586 (95% CI, 0.419-0.753) using uterine volumes obtained by 3D-US and by 2D-US, respectively, and they were 0.938 (95% CI, 0.879-0.996) and 0.815 (95% CI, 0.681-0.948) using 3D-US and 2D-US volumes alone. CONCLUSIONS: The need to morcellate can be predicted preoperatively using 3D-US uterine volumes obtained by transvaginal US with a fair degree of accuracy. Uteri with volumes smaller than 120 mL at 3D-US are very unlikely to require morcellation. The incorporation of 3D-US-estimated uterine volume into the previously published logistic regression model does not seem to confer any significant improvement when compared with 3D-US uterine volume alone to predict the need to morcellate in women undergoing total LH. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 27281512 TI - Riboflavin and ultraviolet light: impact on dengue virus infectivity. AB - BACKGROUND: Dengue viruses (DENV 1-4) are emerging across the world, and these viruses pose a risk to transfusion safety. Pathogen inactivation may be an alternative approach for managing the risk of DENV transfusion transmission. This study aimed to investigate the ability of riboflavin and UV light to inactivate DENV 1-4 in platelet concentrates. MATERIALS AND METHODS: DENV 1-4 were spiked into buffy coat-derived platelet concentrates in additive solution (SSP+) before being treated with riboflavin and UV light. Infectious virus was quantified pre- and posttreatment, and the reduction in viral infectivity was calculated. RESULTS: All four DENV serotypes were modestly reduced after treatment. The greatest amount of reduction in infectivity was observed for DENV-4 (1.81 log reduction) followed by DENV-3 (1.71 log reduction), DENV-2 (1.45 log reduction) and then DENV-1 (1.28 log reduction). CONCLUSION: Our study demonstrates that DENV 1-4 titres are modestly reduced following treatment with riboflavin and UV light. With the increasing number of transfusion-transmitted cases of DENV around the globe, and the increasing incidence and geographical distribution of DENV, additional approaches for maintaining blood safety may be required in the future. PMID- 27281514 TI - An examination of the roles played by early adolescent children in interactions with their local food environment. AB - OBJECTIVES: The purpose of this study was to examine how pre- and early adolescent (10-14 years old) children from a wide range of neighbourhoods interact with their local food environment (FE), with a focus on the foods and food sources they access and their locations. Children in this age group are developing independence and mobility within (and beyond) their home neighbourhoods but are somewhat geographically bound as they cannot yet drive. METHODS: This research consists of qualitative interviews with 31 children (15 males, 16 females) aged 10-14 years living in socio-economically diverse neighbourhoods across Saskatoon, SK. A thematic analysis was conducted. RESULTS: Children's descriptions of what constitutes their neighbourhood FE were varied, ranging from a couple of city blocks to several kilometres from home. Children were familiar with the types of establishment that sell food within their perceived neighbourhood. When children purchased their own food they most frequently cited buying snacks such as ice cream, candy and slushes, and the majority of these purchases were made in convenience stores, gas stations and grocery stores. Few children reported frequenting fast-food or other restaurants without adults, and when they did it was usually to buy snacks such as French fries and ice cream rather than meals. CONCLUSIONS: Our results highlight the importance of interventions targeted to this age group, in which personal food choices were reported almost exclusively as being energy- but not nutrient-dense snack foods. PMID- 27281515 TI - The food environment and diet quality of urban-dwelling older women and men: Assessing the moderating role of diet knowledge. AB - OBJECTIVES: The relationships between local food environments and dietary patterns are important for older adults and could be different in men and women. We examined associations between exposure to neighbourhood food sources and food consumption and the moderating role of diet knowledge separately among older women and men living in Montreal in 2003-2005 (n = 722). METHODS: The proportion of fast-food outlets relative to all restaurants (%FFO) and the proportion of healthy food stores relative to all stores (%HFS) were estimated for 500 m buffers around participants' homes. Two dietary patterns, designated "Western" and "prudent", reflecting lower- and higher-quality diets respectively, were identified from food frequency questionnaire data. The unique and interactive effects of diet knowledge and food-source exposure on diet scores were tested with separate linear regression models for women and men. RESULTS: For men, greater %FFO exposure was related to lower prudent diet scores (beta = -0.18, p = 0.02), but no effect of %HFS exposure was observed and no interactions were statistically significant. For women, an inverse relationship between %FFO and prudent diet scores was strongest among those with low diet knowledge (beta = 0.22, p < 0.01). No other associations were statistically significant. CONCLUSION: Older men's diet patterns may reflect unhealthy cues associated with fast-food outlets. Among women, diet knowledge potentiated both negative and positive relationships with the food environment. In the absence of consistent main effects of the food environment on diet scores, subgroup analysis is a promising avenue for research. PMID- 27281516 TI - Exploring experiences of the food environment among immigrants living in the Region of Waterloo, Ontario. AB - OBJECTIVES: This exploratory study aimed to shed light on the role of the food environment in shaping food access among immigrants living in the Region of Waterloo, Ontario. METHODS: In this qualitative case study, in-depth interviews aided by photovoice were conducted with nine immigrants, and key informant (KI) interviews were conducted with nine community stakeholders (e.g., settlement workers, planners) who held expert knowledge of the local context with respect to both the food system and experiences of immigrants in interacting with this system. In this paper, we focus specifically on insights related to the food environment, applying the Analysis Grid for Environments Linked to Obesity Framework to assess economic, physical, socio-cultural and political aspects. RESULTS: Economic features of the food environment, including food prices and differential costs of different types of food, emerged as factors related to food access. However, interactions with the food environment were shaped by broader economic factors, such as limited employment opportunities and low income. Most immigrants felt that they had good geographic access to food, though KIs expressed concerns about the types of outlet and food that were most accessible. Immigrants discussed social networks and cultural food practices, whereas KIs discussed political issues related to supporting food security in the Region. CONCLUSION: This exploratory case study is consistent with prior research in highlighting the economic constraints within which food access exists but suggests that there may be a need to further dissect food environments. PMID- 27281517 TI - Relative and absolute availability of fast-food restaurants in relation to the development of diabetes: A population-based cohort study. AB - OBJECTIVES: To determine whether residents living in areas with a high proportion of fast-food restaurants (FFR) relative to all restaurants are more likely to develop diabetes and whether the risk varies according to the volume of FFR. METHODS: The study cohort consisted of adult respondents (20-84 years) to the Canadian Community Health Survey (cycles 2005, 2007/2008, 2009/2010) who resided within walking distance (720 m) of at least one restaurant in Toronto, Brampton, Mississauga or Hamilton, ON. The development of diabetes was established by linking participants to the Ontario Diabetes Database. Cox proportional hazards models were used to estimate hazard ratios (HRs) of incident diabetes associated with relative and absolute measures of restaurant availability. RESULTS: During a median follow-up of 5 years, 347 of 7,079 participants (4.6%) developed diabetes. Among younger adults (20-65 years, n = 5,806), a greater proportion of fast-food relative to all restaurants was significantly associated with incident diabetes after adjustment for a range of individual and area-level covariates, but only in areas with high volumes of fast-food retailers (3+ outlets) (HR = 1.79, 95% confidence interval: 1.03-3.12, across the interquartile range). Adjusting for body mass index rendered this association non-significant. No significant associations were observed in areas with low volumes of FFR or among older adults (65-84 years, n = 1,273). Absolute availability (number) of fast-food and other restaurants was generally unrelated to incident diabetes. CONCLUSION: Areas with the double burden of a high volume of FFR and few dining alternatives may represent an adverse environment for the development of diabetes. PMID- 27281518 TI - Challenges in assessing food environments in northern and remote communities in Canada. AB - Effective tools for retail food environments in northern and remote communities are lacking. This paper examines the challenges of conducting food environment assessments in northern and remote communities in Canada encountered during our experience with a food costing project. One of the goals of the Paying for Nutrition in the North project is to develop guidelines to improve current food costing tools for northern Canada. Paying for Nutrition illustrates the complex context of measuring food environments in northern and remote communities. Through the development of a food costing methodology guide to assess northern food environments, several contextual issues emerged, including retail store oligopolies in communities; the importance of assessing food quality; informal social food economies; and the challenge of costing the acquisition and consumption of land- and water-based foods. Food environment measures designed for northern and remote communities need to reflect the geographic context in which they are being employed and must include input from local residents. PMID- 27281519 TI - Policy options for healthier retail food environments in city-regions. AB - Public policy is central to health promotion: it determines the distribution of resources in a society and establishes the structural context for the actions of both corporations and consumers. With this in mind, the purpose of this paper is to begin a discussion on promising policy options for a health-promoting retail food environment. Drawing on specific municipal examples, we examine four groups of policy options for healthier retail food environments in city-regions: planning for health; transforming consumer environments; economic and fiscal instruments; and a culture of transparency and participation. We introduce examples of policy options that are receiving increasing attention in the public health and urban planning literature and that function at the municipal level. We also highlight how public health professionals have an important role to play in policy that shapes retail food environments, especially in making explicit the linkages between health and other policy goals. In doing so, this commentary aims to motivate public health practitioners in a variety of community contexts to consider the policy supports they need to advance their exploration, development, testing and evaluation of interventions for healthier retail food environments. PMID- 27281520 TI - Retail food environments research in Canada: A scoping review. AB - OBJECTIVES: The field of retail food environments research is relatively new in Canada. The objective of this scoping review is to provide an overview of retail food environments research conducted before July 2015 in Canada. Specifically, this review describes research foci and key findings, identifies knowledge gaps and suggests future directions for research. METHODS: A search of published literature concerning Canadian investigations of retail food environment settings (food stores, restaurants) was conducted in July 2015 using PubMed, Web of Science, Scopus, PsychInfo and ERIC. Studies published in English that reported qualitative or quantitative data on any aspect of the retail food environment were included, as were conceptual papers and commentaries. SYNTHESIS: Eighty eight studies were included in this review and suggest that the field of retail food environments research is rapidly expanding in Canada. While only 1 paper was published before 2005, 66 papers were published between 2010 and 2015. Canadian food environments research typically assessed either the socio-economic patterning of food environments (n = 28) or associations between retail food environments and diet, anthropometric or health outcomes (n = 33). Other papers profiled methodological research, qualitative studies, intervention research and critical commentaries (n = 27). Key gaps in the current literature include measurement inconsistency among studies and a lack of longitudinal and intervention studies. CONCLUSION: Retail food environments are a growing topic of research, policy and program development in Canada. Consistent methods (where appropriate), longitudinal and intervention research, and close partnerships between researchers and key stakeholders would greatly advance the field of retail food environments research in Canada. PMID- 27281522 TI - Walkable home neighbourhood food environment and children's overweight and obesity: Proximity, density or price? AB - OBJECTIVES: To identify characteristics of the food environment associated with child overweight/obesity that could, if subjected to intervention, mitigate the risk of childhood overweight/obesity. We examined whether the proximity to or density of grocery and convenience stores or fast food restaurants, or the prices of healthy food options were more strongly associated with overweight/obesity risk in children. METHODS: We collected geocoded data by residential addresses for 1,469 children aged 10-14 years and conducted a census of all food outlets in Saskatoon. The Nutrition Environment Measures Survey (NEMS)-Stores and the NEMS Restaurants were used to measure availability, quality and relative price of healthy food items in stores and restaurants. Children's weight status was calculated on the basis of measured height and weight. Logistic regression was used to test the associations between overweight/obesity and food environment variables. RESULTS: Within an 800 m walking distance from home, 76% of children did not have access to a grocery store; 58% and 32% had access to at least one convenience store or one fast-food restaurant respectively. A significantly lower odds of overweight/obesity was associated with lower price of healthy food items/options in grocery stores (odds ratio [OR] = 0.87, 95% confidence interval [CI] 0.77-0.99) and fast-food restaurants (OR = 0.97, 95% CI 0.95-0.99) within walking distance of home. Neither the distance to the closest food outlet nor the density of food outlets around children's homes was associated with odds of overweight/obesity. CONCLUSIONS: Improving economic access to healthy food in food outlets or fast-food restaurants is one strategy to counter childhood overweight/ obesity. PMID- 27281521 TI - Using GPS and activity tracking to reveal the influence of adolescents' food environment exposure on junk food purchasing. AB - OBJECTIVES: This study examines the influence of adolescents' exposure to unhealthy food outlets on junk food purchasing during trips between home and school, with particular attention to how exposure and purchasing differ according to child's biological sex, mode of transportation, and direction to or from school. METHODS: Between 2010 and 2013, students (n = 654) aged 9-13 years from 25 schools in London and Middlesex County, ON, completed a socio-demographic survey and an activity diary (to identify food purchases), and were observed via a global positioning system for 2 weeks (to track routes for trips to/from school). Spatial data on routes and purchase data were integrated with a validated food outlet database in a geographic information system, and exposure was measured as the minutes a child spent within 50 m of an unhealthy food outlet (i.e., fast food restaurants, variety stores). For trips involving junk food exposure (n = 4588), multilevel logistic regression was used to assess the relationship between exposure and purchasing. RESULTS: Multilevel analyses indicated that adolescents' duration of exposure to unhealthy food outlets between home and school had a significant effect on the likelihood of junk food purchasing. This relationship remained significant when the data were stratified by sex (female/male), trip direction (to/from school) and travel mode (active/car), with the exception of adolescents who travelled by bus. CONCLUSION: Policies and programs that mitigate the concentration of unhealthy food outlets close to schools are critical for encouraging healthy eating behaviours among children and reducing diet-related health issues such as obesity. PMID- 27281523 TI - Identifying rural food deserts: Methodological considerations for food environment interventions. AB - OBJECTIVES: Food insecurity in an important public health issue and affects 13% of Canadian households. It is associated with poor accessibility to fresh, diverse and affordable food products. However, measurement of the food environment is challenging in rural settings since the proximity of food supply sources is unevenly distributed. The objective of this study was to develop a methodology to identify food deserts in rural environments. METHODS: In-store evaluations of 25 food products were performed for all food stores located in four contiguous rural counties in Quebec. The quality of food products was estimated using four indices: freshness, affordability, diversity and the relative availability. Road network distance between all residences to the closest food store with a favourable score on the four dimensions was mapped to identify residential clusters located in deprived communities without reasonable access to a "good" food source. The result was compared with the food desert parameters proposed by the US Department of Agriculture (USDA), as well as with the perceptions of a group of regional stakeholders. RESULTS: When food quality was considered, food deserts appeared more prevalent than when only the USDA definition was used. Objective measurements of the food environment matched stakeholders' perceptions. CONCLUSION: Food stores' characteristics are different in rural areas and require an in-store estimation to identify potential rural food deserts. The objective measurements of the food environment combined with the field knowledge of stakeholders may help to shape stronger arguments to gain the support of decision-makers to develop relevant interventions. PMID- 27281524 TI - Retail food environments research: Promising future with more work to be done. AB - As members of the scientific committee for the Food Environments in Canada conference, we reflect on the current state of food environments research in Canada. We are very encouraged that the field is growing and there have been many collaborative efforts to link researchers in Canada, including the 2015 Food Environments in Canada Symposium and Workshop. We believe there are 5 key challenges the field will need to collectively address: theory and causality; replication and extension; consideration of rural, northern and vulnerable populations; policy analysis; and intervention research. In addressing the challenges, we look forward to working together to conduct more sophisticated, complex and community-driven food environments research in the future. PMID- 27281525 TI - Retail food environments in Canada: Maximizing the impact of research, policy and practice. AB - Retail food environments are gaining national and international attention as important determinants of population dietary intake. Communities across Canada are beginning to discuss and implement programs and policies to create supportive retail food environments. Three considerations should drive the selection of food environment assessment methods: relevance (What is the problem, and how is it related to dietary outcomes?); resources (What human, time and financial resources are required to undertake an assessment?); and response (How will policy-makers find meaning out of and act on the information gained through the food environment assessment?). Ultimately, food environment assessments should be conducted in the context of stakeholder buy-in and multi-sectoral partnerships, since food environment solutions require multi-sectoral action. Partnerships between public health actors and the food and beverage industry can be challenging, especially when mandates are not aligned. Clarifying the motivations, expectations and roles of all stakeholders takes time but is important if the impact of food environment research, policy and practice is to be maximized. The articles contained in this special supplementary issue describe ongoing food environments research across Canada and fill some of the important gaps in the current body of Canadian food environments literature. PMID- 27281526 TI - Retail Food Environments in Canada. AB - No abstract available. PMID- 27281528 TI - Sex differences exist after intracerebral hemorrhage but may not affect outcome. PMID- 27281527 TI - Sex-related differences in primary intracerebral hemorrhage. AB - OBJECTIVE: Little information is available about sex-related differences in intracerebral hemorrhage (ICH). This is a prospective observational study to describe the sex differences in demographics, vascular risk factors, stroke care, and outcomes in primary ICH. METHODS: BasicMar is a hospital-based registry of all stroke patients admitted to a single public hospital that covers a population of 330,000. From 2005 to 2015, there were 515 consecutive acute primary ICH patients. Outcome data were obtained at 3 months. RESULTS: More men than women had ICH (52.4% vs 47.6%); the women were older and had worse previous functional status than men, who were more likely to drink alcohol and smoke and to have ischemic heart disease and peripheral arterial disease. There were no sex differences in etiology, severity, or hemorrhage volume. ICH score was greater in women than in men (p = 0.018). Women had more lobar ICH than men (odds ratio adjusted by age was 1.75 [95% confidence interval 1.18-2.58], p = 0.005). The quality of stroke care was similar in both sexes. Mortality at 3 months was 44.1% in women and 41.1% in men (p = 0.656), and 3-month poor outcome among survivors (modified Rankin Scale [mRS] score 3-5) 58.4% in women and 45.3% in men (p = 0.027). After adjustment for previous mRS and ICH score, there were no differences in 3-month mortality or poor outcome at 3 months between sexes. CONCLUSIONS: Patients with ICH showed sex-related differences in demographic characteristics, ICH location, and vascular risk factors, but not in stroke care, 3-month mortality, or adjusted poor outcome. PMID- 27281529 TI - Motor plasticity after extra-intracranial bypass surgery in occlusive cerebrovascular disease. AB - OBJECTIVE: To explore plasticity in patients scheduled for extra-intracranial bypass surgery due to unilateral symptomatic occlusive cerebrovascular disease via navigated transcranial magnetic stimulation. METHODS: In this observational study, patients were allocated to different substudies and examined before and 3 months after operation. (1) Corticospinal excitability was determined via identification of the resting motor threshold. (2) Intracortical inhibition and facilitation were tested by paired pulse transcranial magnetic stimulation. (3) Area of cortical representation of the first dorsal interosseous muscle was identified. RESULTS: (1) Resting motor thresholds were higher in the affected hemispheres with impaired cerebrovascular reserve capacity compared to the unaffected hemispheres (45.7% +/- 2.2% compared to 39.2% +/- 1.4%, n = 39, p < 0.05). Reduced excitability normalized 3 months after revascularization (51% +/- 2.6% -> 45% +/- 1.9%, n = 21, p < 0.05). (2) In paired pulse paradigms, there was a motor disinhibition in the operated hemispheres. (3) There was a reduction of the cortical representation areas of the first dorsal interosseous muscle (2.3 +/ 0.5 cm(2) -> 0.9 +/- 0.6 cm(2), n = 9, p < 0.05) after operation. CONCLUSIONS: Our data demonstrate a reversibly impaired motor cortical function in the chronically ischemic brain. In carefully selected patients, cerebral revascularization leads to improved motor output indicated by a lower resting motor threshold, intracortical disinhibition, and more focused motor cortical representation. PMID- 27281530 TI - Anti-NMDA receptor antibody encephalitis and neuroendocrine pancreatic tumor: Causal link? PMID- 27281531 TI - TEV-48125 for the preventive treatment of chronic migraine: Efficacy at early time points. AB - OBJECTIVE: To evaluate the onset of efficacy of TEV-48125, a monoclonal antibody against calcitonin gene-related peptide, recently shown to be effective for the preventive treatment of chronic migraine (CM) and high-frequency episodic migraine. METHODS: A randomized placebo-controlled study tested once-monthly injections of TEV-48125 675/225 mg or 900 mg vs placebo. Headache information was captured daily using an electronic headache diary. The primary endpoint was change from baseline in the number of headache hours in month 3. Herein, we assess the efficacy of each dose at earlier time points. RESULTS: The sample consisted of 261 patients. For headache hours, the 675/225-mg dose separated from placebo on day 7 and the 900-mg dose separated from placebo after 3 days of therapy (p = 0.048 and p = 0.033, respectively). For both the 675/225-mg and 900 mg doses, the improvement was sustained through the second (p = 0.004 and p < 0.001) and third (p = 0.025 and p < 0.001) weeks of therapy and throughout the study (month 3, p = 0.0386 and p = 0.0057). For change in weekly headache days of at least moderate intensity, both doses were superior to placebo at week 2 (p = 0.031 and p = 0.005). CONCLUSIONS: TEV-48125 demonstrated a significant improvement within 1 week of therapy initiation in patients with CM. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CM, TEV-48125 significantly decreases the number of headache hours within 3 to 7 days of injection. PMID- 27281532 TI - Novel motor phenotypes in patients with VRK1 mutations without pontocerebellar hypoplasia. AB - OBJECTIVE: To describe the phenotypes in 2 families with vaccinia-related kinase 1 (VRK1) mutations including one novel VRK1 mutation. METHODS: VRK1 mutations were found by whole exome sequencing in patients presenting with motor neuron disorders. RESULTS: We identified pathogenic mutations in the VRK1 gene in the affected members of 2 families. In family 1, compound heterozygous mutations were identified in VRK1, c.356A>G; p.H119R, and c.1072C>T; p.R358*, in 2 siblings with adult onset distal spinal muscular atrophy (SMA). In family 2, a novel VRK1 mutation, c.403G>A; p.G135R and c.583T>G; p.L195V, were identified in a child with motor neuron disease. CONCLUSIONS: VRK1 mutations can produce adult-onset SMA and motor neuron disease in children without pontocerebellar hypoplasia. PMID- 27281533 TI - TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features. AB - OBJECTIVE: To evaluate the phenotypic spectrum associated with mutations in TBC1D24. METHODS: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24). RESULTS: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function. CONCLUSIONS: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes. PMID- 27281535 TI - Comment: Monoclonal antibodies in chronic migraine-Are early effects meaningful? PMID- 27281534 TI - A low-cost, tablet-based option for prehospital neurologic assessment: The iTREAT Study. AB - OBJECTIVES: In this 2-center study, we assessed the technical feasibility and reliability of a low cost, tablet-based mobile telestroke option for ambulance transport and hypothesized that the NIH Stroke Scale (NIHSS) could be performed with similar reliability between remote and bedside examinations. METHODS: We piloted our mobile telemedicine system in 2 geographic regions, central Virginia and the San Francisco Bay Area, utilizing commercial cellular networks for videoconferencing transmission. Standardized patients portrayed scripted stroke scenarios during ambulance transport and were evaluated by independent raters comparing bedside to remote mobile telestroke assessments. We used a mixed effects regression model to determine intraclass correlation of the NIHSS between bedside and remote examinations (95% confidence interval). RESULTS: We conducted 27 ambulance runs at both sites and successfully completed the NIHSS for all prehospital assessments without prohibitive technical interruption. The mean difference between bedside (face-to-face) and remote (video) NIHSS scores was 0.25 (1.00 to -0.50). Overall, correlation of the NIHSS between bedside and mobile telestroke assessments was 0.96 (0.92-0.98). In the mixed-effects regression model, there were no statistically significant differences accounting for method of evaluation or differences between sites. CONCLUSIONS: Utilizing a low-cost, tablet-based platform and commercial cellular networks, we can reliably perform prehospital neurologic assessments in both rural and urban settings. Further research is needed to establish the reliability and validity of prehospital mobile telestroke assessment in live patients presenting with acute neurologic symptoms. PMID- 27281537 TI - Acute stroke in the field: iTREAT, you treat, we all one day will treat ... better. PMID- 27281538 TI - Efficient Targeting of Adipose Tissue Macrophages in Obesity with Polysaccharide Nanocarriers. AB - Obesity leads to an increased risk for type 2 diabetes, heart disease, stroke, and cancer. The causal link between obesity and these pathologies has recently been identified as chronic low-grade systemic inflammation initiated by pro inflammatory macrophages in visceral adipose tissue. Current medications based on small-molecule drugs yield significant off-target side effects with long-term use, and therefore there is a major need for targeted therapies. Here we report that nanoscale polysaccharides based on biocompatible glucose polymers can efficiently target adipose macrophages in obese mice. We synthesized a series of dextran conjugates with tunable size linked to contrast agents for positron emission tomography, fluorophores for optical microscopy, and anti-inflammatory drugs for therapeutic modulation of macrophage phenotype. We observed that larger conjugates efficiently distribute to visceral adipose tissue and selectively associate with macrophages after regional peritoneal administration. Up to 63% of the injected dose remained in visceral adipose tissue 24 h after administration, resulting in >2-fold higher local concentration compared to liver, the dominant site of uptake for most nanomedicines. Furthermore, a single-dose treatment of anti-inflammatory conjugates significantly reduced pro-inflammatory markers in adipose tissue of obese mice. Importantly, all components of these therapeutic agents are approved for clinical use. This work provides a promising nanomaterials-based delivery strategy to inhibit critical factors leading to obesity comorbidities and demonstrates a unique transport mechanism for drug delivery to visceral tissues. This approach may be further applied for high efficiency targeting of other inflammatory diseases of visceral organs. PMID- 27281539 TI - Application of microwave irradiation for the removal of polychlorinated biphenyls from siloxane transformer and hydrocarbon engine oils. AB - The removal of polychlorinated biphenyls (PCBs) both from siloxane transformer oil and hydrocarbon engine oil was investigated through the application of microwave (MW) irradiation and a reaction system based on polyethyleneglycol (PEG) and potassium hydroxide. The influence of the main reaction parameters (MW irradiation time, molecular weight of PEG, amount of added reactants and temperature) on the dechlorination behavior was studied. Promising performances were reached, allowing about 50% of dechlorination under the best experimental conditions, together time and energy saving compared to conventional heating systems. Moreover, an interesting dechlorination degree (up to 32%) was achieved for siloxane transformer oil when MW irradiation was employed as the unique driving force. To the best of our knowledge, this is the first time in which MW irradiation is tested as the single driving force for the dechlorination of these two types of PCB-contaminated oils. PMID- 27281536 TI - The genetic basis of undiagnosed muscular dystrophies and myopathies: Results from 504 patients. AB - OBJECTIVE: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients. METHODS: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy. RESULTS: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes. CONCLUSIONS: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions. PMID- 27281540 TI - Ultrasensitive detection of inhaled organic aerosol particles by accelerator mass spectrometry. AB - Accelerator mass spectrometry (AMS) was shown to be applicable for studying the penetration of organic aerosols, inhaled by laboratory mice at ultra-low concentration ca. 10(3) cm(-3). We synthesized polystyrene (PS) beads, composed of radiocarbon-labeled styrene, for testing them as model organic aerosols. As a source of radiocarbon we used methyl alcohol with radioactivity. Radiolabeled polystyrene beads were obtained by emulsifier-free emulsion polymerization of synthesized (14)C-styrene initiated by K2S2O8 in aqueous media. Aerosol particles were produced by pneumatic spraying of diluted (14)C-PS latex. Mice inhaled (14)C PS aerosol consisting of the mix of 10(3) 225-nm particles per 1 cm(3) and 5.10(3) 25-nm particles per 1 cm(3) for 30 min every day during five days. Several millions of 225-nm particles deposited in the lungs and slowly excreted from them during two weeks of postexposure. Penetration of particles matter was also observed for liver, kidneys and brain, but not for a heart. PMID- 27281541 TI - Improving the accuracy of hand-held X-ray fluorescence spectrometers as a tool for monitoring brominated flame retardants in waste polymers. AB - An optimised method for Br quantification as a metric of brominated flame retardant (BFR) concentrations present in Waste Electrical and Electronic Equipment (WEEE) polymers is proposed as an alternative to the sophisticated, yet time consuming GC-MS methods currently preferred. A hand-held X-ray fluorescence (XRF) spectrometer was validated with Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Customized standard materials of specific BFRs in a styrenic polymer were used to perform an external calibration for hand-held XRF ranging from 0.08 to 12 wt% of Br, and cross-checking with LA-ICP-MS having similar LODs (0.0004 wt% for LA-ICP-MS and 0.0011 wt% for XRF). The "thickness calibration" developed here for hand-held XRF and the resulting correction, was applied to 28 real samples and showed excellent (R(2) = 0.9926) accordance with measurements obtained via LA-ICP-MS. This confirms the validity of hand-held XRF as an accurate technique for the determination of Br in WEEE plastics. This is the first use of solid standards to develop a thickness-corrected quantitative XRF measurement of Br in polymers using LA-ICP-MS for method evaluation. Thermal desorption gas chromatography mass spectrometry (TD-GC-MS) was used to confirm the presence of specific BFRs in WEEE polymer samples. We propose that expressing limit values for BFRs in waste materials in terms of Br rather than BFR concentration (based on a conservative assumption about the BFR present), presents a practical solution to the need for an accurate, yet rapid and inexpensive technique capable of monitoring compliance with limit values in situ. PMID- 27281542 TI - Environmental organic pollutants in human milk before and after weight loss. AB - Many persistent organic pollutants (POPs) are banned because they accumulate in organisms and are toxic. Lipophilic POPs are stored in maternal adipose tissue and concentrations in human milk (HM) may increase during weight loss. Our aim was to examine associations between weight loss and concentrations of chlorinated POPs in HM in lactating women participating in a weight loss study. We analysed POPs (PCB 28, PCB 153, HCB, DDE) in HM at 12 and 24 weeks postpartum from 32 women who participated in a randomized, 2 * 2 factorial trial of diet and exercise for postpartum weight loss. Participants donated milk before and after the intervention period. We examined associations between weight loss and change in POP concentrations and estimated the intake of POPs by their breastfed infants. Most (n = 27) women lost weight during intervention, 0.45 +/- 0.30 kg/week (mean +/- SD). Among these women, the concentration of PCB 153 in HM was significantly (p = 0.04) higher at follow-up than at baseline. Weight loss was significantly positively associated with changes in concentrations of all studied POPs (2.0-2.4% increase per percent weight loss). Estimated mean intakes of POPs (ng/day) remained stable because infant milk consumption decreased during the study period. As infants gained weight, estimated mean intakes per kg body weight decreased 17-22%. Changes in concentrations of POPs in HM correlated positively with maternal weight loss, but it is unlikely that the balance between the benefits and risks of breastfeeding will change if the weight loss is restricted to 0.5 kg per week. PMID- 27281544 TI - Mechanisms of interaction between persistent organic pollutants (POPs) and CYP2B6: An in silico approach. AB - Human Cytochrome P450s (CYP450) are a group of heme-containing metalloenzymes responsible for recognition and metabolism of numerous xenobiotics, including drugs and environmental contaminants. CYP2B6, a member of CYP450, is well known for being a highly inducible and polymorphic enzyme and for its important role in the oxidative metabolism of environmental pollutants, such as the Polybrominated Diphenyl Ethers (PBDEs) and Polychlorinated Biphenyls (PCBs). However the mechanisms of interaction of PBDEs and PCBs with CYP2B6 is not entirely known. In this work, a computational approach was carried out to study the interactions of 41 POPs (17 PBDEs, 17 PCBs, and 7 Dioxins) with four CYP2B6 protein structures downloaded from PDB data base (PDB: 3UA5, 3QOA, 3QU8 and 4I91) using molecular docking protocols with AutoDock Vina. The best binding affinity values (kcal/mol) were obtained for PBDE-99 (-8.5), PCB-187 (-9.6), and octachloro-dibenzo-dioxin ( 9.8) that can be attributed to the hydrophobic interactions with important residues, such as Phe-363, in the catalytic site of CYP2B6. Molecular docking validation revealed the best values for PDB: 3UA5 (R = 0.622, p = 0.001) demonstrating the reliability of molecular docking predictions. The information obtained in this work can be useful in evaluating the modes of interaction of xenobiotic compounds with the catalytic site of CYP2B6 and provide insights on the important role of these enzymes in the metabolism of potentially toxic compounds in humans. PMID- 27281543 TI - Sorption of roxarsone onto soils with different physicochemical properties. AB - Elevated roxarsone (ROX) concentrations in soils, caused by land application of ROX-bearing poultry litter, mandate investigation of ROX sorption onto soils. Equilibrium and kinetic studies of ROX sorption onto five soils were carried out to explore the relationship between sorption parameters and soil properties, and to reveal the effects of coexisting humic acid (HA), P(V), As(V), and As(III) on ROX transport. Experimental results indicated that ROX sorption reached equilibrium within 24 h, with pseudo-second order rate constants of 5.74-5.26 * 10(2) g/(mg h); film and intra-particle diffusion were the rate-limiting processes. ROX sorption to soils involved partitioning and adsorption phenomena; however, their relative contributions varied for different soils. The maximum ROX sorption varied with soil type, ranging from 0.59 to 4.12 mg/g. Results from correlation analysis and multiple linear regressions revealed that the maximum sorption capacities, partition coefficients, and desorption percentages were correlated with soil properties, especially iron content, total organic carbon, and dissolved organic carbon. ROX sorption to soils was affected more by soil pH than the initial pH of ROX-containing solutions. Carboxylic and amide functional groups were determined to be responsible for ROX sorption to soils. ROX sorption capacities decreased in the presence of HA, P(V), As(V), and As(III), indicating that ROX mobility in soils was facilitated by dissolved organic matter (DOM) and competing anions. PMID- 27281545 TI - Mechanism of Fluorescence Switching in One ESIPT-Based Al(3+) Probe. AB - A recently synthesized Schiff base used as a probe for aluminum cations was studied with ab initio models. The primary reason for the lack of fluorescence in aprotic solvents was found to be the presence of an efficient conical intersection (CI) between the ground-states and the first singlet excited-states close to the Franck-Condon geometry. The excited-state pathway leading to this CI is barrierless but implies large amplitude motions, explaining why the fluorescence was observed in frozen acetonitrile matrix. Our calculations suggest that constraining the molecule by impending the rotation around the imino bond enables excited-state intramolecular proton transfer. A similar stiffening mechanism is responsible for the strong fluorescence turn-on after formation of complexes between Al(3+) cations and dehydrogenated Schiff base. Finally, the analysis of the possible fluorescence mechanisms in water indicates that the anion of 1 is the likely fluorescence source. Overall, this work allows one to disentangle the various origins of fluorescence switching in a probe. PMID- 27281546 TI - Electrocatalytic Reduction of CO2 to CO With Re-Pyridyl-NHCs: Proton Source Influence on Rates and Product Selectivities. AB - A series of four electron-deficient-substituted Re(I) pyridyl N-heterocyclic carbene (pyNHC) complexes have been synthesized, and their electrocatalytic reduction of CO2 has been evaluated by cyclic voltammetry and controlled potential electrolysis experiments. All of the catalysts were evaluated by cyclic voltammetry under inert atmosphere and under CO2 and compared to the known benchmark catalyst Re(bpy)(CO)3Br. Among the four Re-NHC catalysts, Re(pyNHC PhCF3)(CO)3Br (2) demonstrated the highest catalytic rate (icat/ip)(2) at the first and second reduction events with a value of 4 at the second reduction potential (TOF = 0.8 s(-1)). The rate of catalysis was enhanced through the addition of proton sources (PhOH, TFE, and H2O; TOF up to 100 s(-1); (icat/ip)(2) = 700). Controlled potential electrolysis shows Faradaic efficiencies (FE) for CO production and accumulated charge for the Re(pyNHC-PhCF3)(CO)3Br catalyst exceed those of the benchmark catalyst in the presence of 2 M H2O (92%, 13 C at 1 h versus 61%, 3 C for the benchmark catalyst) under analogous experimental conditions. A peak FE of 100% was observed during electrolysis with Re(pyNHC PhCF3)(CO)3Br. PMID- 27281547 TI - Partially Hydrated Electrons at the Air/Water Interface Observed by UV-Excited Time-Resolved Heterodyne-Detected Vibrational Sum Frequency Generation Spectroscopy. AB - Hydrated electrons are the most fundamental anion species, consisting only of electrons and surrounding water molecules. Although hydrated electrons have been extensively studied in the bulk aqueous solutions, even their existence is still controversial at the water surface. Here, we report the observation and characterization of hydrated electrons at the air/water interface using new time resolved interface-selective nonlinear vibrational spectroscopy. With the generation of electrons at the air/water interface by ultraviolet photoirradiation, we observed the appearance of a strong transient band in the OH stretch region by heterodyne-detected vibrational sum-frequency generation. Through the comparison with the time-resolved spectra at the air/indole solution interface, the transient band was assigned to the vibration of water molecules that solvate electrons at the interface. The analysis of the frequency and decay of the observed transient band indicated that the electrons are only partially hydrated at the water surface, and that they escape into the bulk within 100 ps. PMID- 27281548 TI - Ex Vivo Treatment with a Polyphenol-Enriched Cocoa Extract Ameliorates Myocardial Infarct and Postischemic Mitochondrial Injury in Normotensive and Hypertensive Rats. AB - Our objective was to determine the effects of a polyphenol-enriched cocoa extract (PCE) on myocardial postischemic alterations in normotensive (Wistar rats, W) and spontaneously hypertensive rats (SHR). Isolated hearts were submitted to 110 min of perfusion or 20 min stabilization, 30 min global ischemia, and 60 min reperfusion (R). Other hearts were treated with PCE at the onset of R. Infarct size, the reduced glutathione (GSH), and the expression of phospho-Akt, P-GSK 3beta, and P-eNOS were assessed. In isolated mitochondria, the Ca(2+)-mediated response of mitochondrial permeability transition pore (mPTP), membrane potential (Deltapsim), and superoxide production were determined. PCE decreased infarct size, partly preserved GSH, increased the P-Akt, P-GSK-3beta, and P-eNOS contents, improved mPTP response to Ca(2+), decreased the superoxide production, and restored Deltapsim. These data show that PCE decreases the cardiac postischemic damage in W rats and SHR and suggest that Akt/GSK-3beta/eNOS dependent pathways are involved. PMID- 27281549 TI - Publication ethics and COPE. PMID- 27281550 TI - Chemical and biological methods to evaluate the availability of heavy metals in soils of the Siena urban area (Italy). AB - A biogeochemistry field study was conducted in the Siena urban area (Italy) with the main objective of establishing the relationship between available amounts of heavy metals in soil assessed by a chemical method (soil fractionation) and bioavailability assessed by a biological method (bioaccumulation in earthworm tissues). The total content of traffic-related (Cd, Cu, Pb, Sb, Zn) and geogenic (Co, Cr, Ni, U) heavy metals in uncontaminated and contaminated soils and their concentrations in soil fractions and earthworms were used for this purpose. The bioavailability of heavy metals assessed by earthworms did not always match the availability defined by soil fractionation. Earthworms were a good indicator to assess the bioavailability of Pb and Sb in soil, while due to physiological mechanisms of regulation and excretion, Cd, Cu and Zn tissue levels in these invertebrates gave misleading estimates of their bioavailable pool. No relationship was identified between chemical and biological availability for the geogenic heavy metals, characterized by a narrow range of total contents in soil. The study highlighted that chemical and biological methods should be combined to provide more complete information about heavy element bioavailability in soils. PMID- 27281551 TI - Insecticides in sediment cores from a rural and a suburban area in South China: A reflection of shift in application patterns. AB - A shift in pesticide application pattern has occurred in recent decades, yet little information is available in the consequence of this shift. To better understand how the shift is reflected in aquatic environment, two sediment cores were collected from a rural (RLY) and a suburban (SGZ) river in South China. A variety of legacy organochlorine pesticides (OCPs) and current-use pesticides (CUPs), including organophosphate, pyrethroid and phenylpyrazole insecticides were quantified at distinct increments of the sediment cores. Total insecticide concentrations were in the ranges of 67.6-1671 and 99.2-231ng/g dry weight in RLY and SGZ with pyrethroids and organochlorines being the dominant components, respectively. In general, the shifting profile of sediment-bound insecticides from legacy OCPs to CUPs over time followed their historical application pattern, but significant differences were noted between the temporal profiles of the rural and suburban cores in regards to concentrations and composition of insecticides. The observed difference between the suburban and rural cores was synchronous with land use pattern and local economic changes. A steep increased occurrence of CUPs in the 1990s was observed in the RLY core, which is consistent with the onset of economic growth in this area. In contrast, the suburban SGZ area has been historically contaminated by legacy OCPs, with fresh input of OCPs in SGZ believed to be caused by soil erosion, caused by land reclamation activities associated with urban expansion. The current study shows the shift in insecticide application pattern from legacy OCPs to CUPs leading to an elevated CUP occurrence in the environment. It also suggests a stronger need for understanding not only environmental fate and risk, but also how their use pattern and land use changes impact the occurrence of pesticides. PMID- 27281552 TI - ALK Expression in Melanomas: Looking for a Needle in a Haystack. PMID- 27281553 TI - Trading off accountability against professional survival? Or the consequences of Pareto's principle.... PMID- 27281554 TI - Remineralizing Agents: The Next Frontier. AB - Remineralizing agents represent a new frontier in dentistry. They may be classified as fluoride agents, calcium and phosphate based agents, herbal agents or combinations. The modes of delivery of remineralizing agents may be as dentifrices, mouth rinses, lozenges or chewing gums. The applications of remineralizing agents may be extrapolated to virtually every branch of dentistry ranging from pediatric to geriatric dentistry. PMID- 27281555 TI - Cobalt-Catalyzed Peroxidation of 2-Oxindoles with Hydroperoxides. AB - A highly efficient and facile cobalt-catalyzed C-H activation and peroxidation of 2-oxindoles was reported, which provides a new pathway for the synthesis of biologically active 3-peroxy-2-oxindoles from readily available starting materials in excellent chemical yields. The resulting products could be further transformed into various substituted 3-peroxyoxindoles in good to excellent yields. The developed method has been successfully applied to the synthesis of the natural product (+/-)-N-[2-(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3 yl)ethyl]acetamide. PMID- 27281556 TI - Prognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib. AB - Importance: The value of the intrinsic subtypes of breast cancer (luminal A, luminal B, human epidermal growth factor receptor 2 [currently known as ERBB2, but referred to as HER2 in this study]-enriched, and basal-like) in the metastatic setting is currently unknown. Objective: To evaluate the association of the intrinsic subtypes of breast cancer with outcome and/or benefit in hormone receptor (HR)-positive metastatic breast cancer. Design, Setting, and Participants: Unplanned retrospective analysis of 821 tumor samples (85.7% primary and 14.3% metastatic) from the EGF30008 phase 3 clinical trial (NCT00073528), in which postmenopausal women with HR-positive invasive breast cancer and no prior therapy for advanced or metastatic disease were randomized to letrozole with or without lapatinib, an epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor. Tumor samples were classified into each subtype using the research-based PAM50 classifier. Prior neoadjuvant/adjuvant antiestrogen therapy was allowed. Patients with extensive symptomatic visceral disease were excluded. Treatment effects were evaluated using interaction tests. Main Outcomes and Measures: Primary and secondary end points were progression free survival and overall survival. Results: The median (range) age was 62 (31 94) years. Intrinsic subtype was the strongest prognostic factor independently associated with progression-free survival and overall survival in all patients, and in patients with HER2-negative (n = 644) or HER2-positive (n = 157) diseases. Median progression-free survival differed across the intrinsic subtypes of clinically HER2-negative disease: luminal A (16.9 [95% CI, 14.1-19.9] months), luminal B (11.0 [95% CI, 9.6-13.6] months), HER2-enriched (4.7 [95% CI, 2.7-10.8] months), and basal-like (4.1 [95% CI, 2.5-13.8] months). Median OS also differed across the intrinsic subtypes: luminal A (45 [95% CI, 41-not applicable {NA}] months), luminal B (37 [95% CI, 31-42] months), HER2-enriched (16 [95% CI, 10-NA] months), and basal-like (23 [95% CI, 12-NA] months). Patients with HER2 negative/HER2-enriched disease benefited from lapatinib therapy (median PFS, 6.49 vs 2.60 months; progression-free survival hazard ratio, 0.238 [95% CI, 0.066 0.863]; interaction P = .02). Conclusions and Relevance: This is the first study to reveal an association between intrinsic subtype and outcome in first-line HR positive metastatic breast cancer. Patients with HR-positive/HER2-negative disease with a HER2-enriched profile may benefit from lapatinib in combination with endocrine therapy. The clinical value of intrinsic subtyping in hormone receptor-positive metastatic breast cancer warrants further investigation, but patients with luminal A/HER2-negative metastatic breast cancer might be good candidates for letrozole monotherapy in the first-line setting regardless of visceral disease and number of metastases. PMID- 27281557 TI - Psychological disorders in adults with inherited cardiomyopathies and Takotsubo syndrome. AB - We performed a narrative review about psychological disorders in adults with Takotsubo syndrome and inherited cardiomyopathies. Through the electronic database PubMed and PsycINFO we searched all relevant related manuscripts published between 2000 and 2015. We found twelve studies that explore psychological disorders in Takotsubo syndrome and eight about inherited cardiomyopathies: five enrolled patients with hypertrophic cardiomyopathy, two dilated cardiomyopathy, and one arrhythmogenic right ventricular cardiomyopathy. All papers reported the presence of psychological disorders. In Takotsubo syndrome, depression fluctuates between 20.5 and 48% and anxiety was present among 26 and 56%. A study reported that anxiety increases the probability of developing Takotsubo syndrome. In dilated cardiomyopathy, anxiety was present in 50% and depression in 22%. In arrhythmogenic right ventricular cardiomyopathy, younger age, poorer functional capacity and having experienced at least one implantable cardioverter defibrillator shock, were significant independent predictors of both device-specific and generalized anxiety. In hypertrophic cardiomyopathy, anxiety and depression were present in 45.2% and 17.9%, respectively. Thirty seven percent met diagnostic criteria for anxiety disorders and 21% for mood disorders. Nearby half hypertrophic cardiomyopathy patients report triggering of chest pain, dyspnea, and dizziness by emotional stress. Due to the small number of studies, conclusions are limited. However, we discuss some results. PMID- 27281559 TI - Clinical Implications of the Pharmacokinetics of Crizotinib in Populations of Patients with Non-Small Cell Lung Cancer. AB - PURPOSE: We assessed the effect of baseline patient demographic and disease characteristics on the crizotinib pharmacokinetic parameters oral clearance (CL/F), volume of distribution (V2/F), and area under the curve at steady state (AUCss) following multiple crizotinib 250-mg twice-daily dosing in patients with ALK-positive cancer. EXPERIMENTAL DESIGN: A pharmacokinetic model was fit to data from 1,214 patients. We identified statistically significant covariates (P <= 0.001) by evaluating their effects on CL/F and V2/F and estimated their magnitudes. RESULTS: Age, Eastern Cooperative Oncology Group performance status, aspartate aminotransferase (AST) levels, albumin levels, and smoking status had no effect on CL/F or V2/F. Statistically significant covariates were Asian race and female sex for CL/F and V2/F and body weight, creatinine clearance (CLcr), and total bilirubin for CL/F only. The model predicted that CL/F would be 9% lower or higher in a 40-kg or a 100-kg patient, respectively; 16% lower in patients with CLcr 30 mL/minute; 23% lower in Asians; and 11% lower in females than the reference patient (65-kg non-Asian male; baseline CLcr, 91.6 mL/minute; total bilirubin, 0.41 mg/dL). The effect of total bilirubin on CL/F was small. V2/F was 23% lower in Asians than non-Asians and females than males. Effects of all significant covariates on AUCss were not predicted to be clinically relevant. CONCLUSIONS: Crizotinib at a 250-mg twice-daily starting dose appears to be appropriate for all patients irrespective of age, sex, race, body weight, mild or moderate renal impairment, or hepatic function (in the range evaluated: bilirubin <= 2.1 mg/dL or AST <=124 U/L). Clin Cancer Res; 22(23); 5722-8. (c)2016 AACR. PMID- 27281562 TI - Love Thy Neighbor: Sharing and Cooperativity in the Gut Microbiota. AB - To persist in the competitive gastrointestinal ecosystem, microbes often enforce selfish strategies that limit resource loss to neighboring bacteria. In contrast, a recent study in Nature by Rakoff-Nahoum et al. (2016) reveals that one commensal bacterium releases nutrients to benefit another species, which reciprocally provides growth-promoting factors to the producer. PMID- 27281561 TI - A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR Mutant Non-Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial. AB - PURPOSE: Genotype-directed therapy is the standard of care for advanced non-small cell lung cancer (NSCLC), but obtaining tumor tissue for genotyping remains a challenge. Circulating tumor cell (CTC) or cell-free DNA (cfDNA) analysis may allow for noninvasive evaluation. This prospective trial evaluated CTCs and cfDNA in EGFR-mutant NSCLC patients treated with erlotinib until progression. EXPERIMENTAL DESIGN: EGFR-mutant NSCLC patients were enrolled in a phase II trial of erlotinib. Blood was collected at baseline, every 2 months on study, and at disease progression. Plasma genotyping was performed by droplet digital PCR for EGFR19del, L858R, and T790M. CTCs were isolated by CellSave, enumerated, and analyzed by immunofluorescence for CD45 and pan-cytokeratin and EGFR and MET FISH were also performed. Rebiopsy was performed at disease progression. RESULTS: Sixty patients were enrolled; 44 patients discontinued therapy for disease progression. Rebiopsy occurred in 35 of 44 patients (80%), with paired CTC/cfDNA analysis in 41 of 44 samples at baseline and 36 of 44 samples at progression. T790M was identified in 23 of 35 (66%) tissue biopsies and 9 of 39 (23%) cfDNA samples. CTC analysis at progression identified MET amplification in 3 samples in which tissue analysis could not be performed. cfDNA analysis identified T790M in 2 samples in which rebiopsy was not possible. At diagnosis, high levels of cfDNA but not high levels of CTCs correlated with progression-free survival. CONCLUSIONS: cfDNA and CTCs are complementary, noninvasive assays for evaluation of acquired resistance to first-line EGFR TKIs and may expand the number of patients in whom actionable genetic information can be obtained at acquired resistance. Serial cfDNA monitoring may offer greater clinical utility than serial monitoring of CTCs. Clin Cancer Res; 22(24); 6010-20. (c)2016 AACR. PMID- 27281560 TI - Inhibition of SOAT1 Suppresses Glioblastoma Growth via Blocking SREBP-1-Mediated Lipogenesis. AB - PURPOSE: Elevated lipogenesis regulated by sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is a novel characteristic of glioblastoma (GBM). The aim of this study was to identify effective approaches to suppress GBM growth by inhibition of SREBP-1. As SREBP activation is negatively regulated by endoplasmic reticulum (ER) cholesterol, we sought to determine whether suppression of sterol O acyltransferase (SOAT), a key enzyme converting ER cholesterol to cholesterol esters (CE) to store in lipid droplets (LDs), effectively suppressed SREBP-1 and blocked GBM growth. EXPERIMENTAL DESIGN: The presence of LDs in glioma patient tumor tissues was analyzed using immunofluorescence, immunohistochemistry, and electronic microscopy. Western blotting and real-time PCR were performed to analyze protein levels and gene expression of GBM cells, respectively. Intracranial GBM xenografts were used to determine the effects of genetically silencing SOAT1 and SREBP-1 on tumor growth. RESULTS: Our study unraveled that cholesterol esterification and LD formation are signature of GBM, and human patients with glioma possess elevated LDs that correlate with GBM progression and poor survival. We revealed that SOAT1 is highly expressed in GBM and functions as a key player in controlling the cholesterol esterification and storage in GBM. Targeting SOAT1 suppresses GBM growth and prolongs survival in xenograft models via inhibition of SREBP-1-regulated lipid synthesis. CONCLUSIONS: Cholesterol esterification and storage in LDs are novel characteristics of GBM, and inhibiting SOAT1 to block cholesterol esterification is a promising therapeutic strategy to treat GBM by suppressing SREBP-1. Clin Cancer Res; 22(21); 5337-48. (c)2016 AACR. PMID- 27281563 TI - The Murky Life of Merkel Cell Polyomavirus. AB - Merkel cell polyomavirus (MCPyV) expressing viral T antigens is a common feature of most Merkel cell carcinomas, a primary neuroendocrine skin tumor. MCPyV has been difficult to propagate in vitro. In this issue of Cell Host & Microbe, Liu et al. (2016) report that human dermal fibroblasts support productive MCPyV infection. PMID- 27281564 TI - African Trypanosomes Find a Fat Haven. AB - The African trypanosome was thought to primarily develop in the bloodstream and interstitial spaces of its mammalian host. In this issue of Cell Host & Microbe, Trindade et al. (2016) report the surprising finding that during ongoing persistent infections in mice, a major fraction of the parasites reside within fatty tissues. PMID- 27281565 TI - The Fungal Mycobiota: Small Numbers, Large Impacts. AB - Fungi are an underappreciated component of the human gut microbiota. In this issue of Cell Host & Microbe, Wheeler et al. (2016) demonstrate that fungal dysbiosis induced by antifungal treatment or inoculation with typically rare fungi results in exaggerated immune responses, suggesting that fungal colonizers play key roles in immune homeostasis. PMID- 27281566 TI - Synthetic Biology Provides a Toehold in the Fight against Zika. AB - The World Health Organization has identified the development of a rapid point-of care diagnostic test for Zika virus as a top research priority. In a recent Cell paper, Pardee et al. (2016) have exploited recent advances in synthetic biology and molecular engineering to deliver a sensitive, affordable, and field-ready Zika test. PMID- 27281567 TI - Pain and Itch: Beneficial or Harmful to Antimicrobial Defense? AB - Pain and itch are unpleasant sensations accompanying many microbial infections. Recent studies demonstrate that pain- and itch-mediating somatosensory neurons are able to directly detect pathogens, triggering neuronal activation and subsequent regulation of immune responses. We discuss whether pain and/or itch during infection is beneficial or harmful to host antimicrobial defense. PMID- 27281568 TI - The Roles of Type I Interferon in Bacterial Infection. AB - Type I interferons (IFNs) are pleiotropic cytokines well recognized for their role in the induction of a potent antiviral gene program essential for host defense against viruses. They also modulate innate and adaptive immune responses. However, the role of type I IFNs in host defense against bacterial infections is enigmatic. Depending on the bacterium, they exert seemingly opposite and capricious functions. In this review, we summarize the effect of type I IFNs on specific bacterial infections and highlight the effector mechanisms regulated by type I IFNs in an attempt to elucidate new avenues to understanding their role. PMID- 27281569 TI - Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality. AB - Herpes simplex virus 1 (HSV-1), a leading cause of genital herpes, infects oral or genital mucosal epithelial cells before infecting the peripheral sensory nervous system. The spread of HSV-1 beyond the sensory nervous system and the resulting broader spectrum of disease are not well understood. Using a mouse model of genital herpes, we found that HSV-1-infection-associated lethality correlated with severe fecal and urinary retention. No inflammation or infection of the brain was evident. Instead, HSV-1 spread via the dorsal root ganglia to the autonomic ganglia of the enteric nervous system (ENS) in the colon. ENS infection led to robust viral gene transcription, pathological inflammatory responses, and neutrophil-mediated destruction of enteric neurons, ultimately resulting in permanent loss of peristalsis and the development of toxic megacolon. Laxative treatment rescued mice from lethality following genital HSV-1 infection. These results reveal an unexpected pathogenesis of HSV associated with ENS infection. PMID- 27281570 TI - Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection. AB - Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine. Both neutralizing and non neutralizing antibodies protected mice in vivo during passive transfer challenge experiments. Mapping the H7 hemagglutinin antigenic sites by generating escape mutant variants against the neutralizing antibodies identified unique epitopes on the head and stalk domains. Further, the broadly cross-reactive non-neutralizing antibodies generated in this study were protective through Fc-mediated effector cell recruitment. These findings reveal important properties of vaccine-induced antibodies and provide a better understanding of the human monoclonal antibody response to influenza in the context of vaccines. PMID- 27281572 TI - The Response of Acinetobacter baumannii to Zinc Starvation. AB - Zinc (Zn) is an essential metal that vertebrates sequester from pathogens to protect against infection. Investigating the opportunistic pathogen Acinetobacter baumannii's response to Zn starvation, we identified a putative Zn metallochaperone, ZigA, which binds Zn and is required for bacterial growth under Zn-limiting conditions and for disseminated infection in mice. ZigA is encoded adjacent to the histidine (His) utilization (Hut) system. The His ammonia-lyase HutH binds Zn very tightly only in the presence of high His and makes Zn bioavailable through His catabolism. The released Zn enables A. baumannii to combat host-imposed Zn starvation. These results demonstrate that A. baumannii employs several mechanisms to ensure bioavailability of Zn during infection, with ZigA functioning predominately during Zn starvation, but HutH operating in both Zn-deplete and -replete conditions to mobilize a labile His-Zn pool. PMID- 27281571 TI - Salmonella Mitigates Oxidative Stress and Thrives in the Inflamed Gut by Evading Calprotectin-Mediated Manganese Sequestration. AB - Neutrophils hinder bacterial growth by a variety of antimicrobial mechanisms, including the production of reactive oxygen species and the secretion of proteins that sequester nutrients essential to microbes. A major player in this process is calprotectin, a host protein that exerts antimicrobial activity by chelating zinc and manganese. Here we show that the intestinal pathogen Salmonella enterica serovar Typhimurium uses specialized metal transporters to evade calprotectin sequestration of manganese, allowing the bacteria to outcompete commensals and thrive in the inflamed gut. The pathogen's ability to acquire manganese in turn promotes function of SodA and KatN, enzymes that use the metal as a cofactor to detoxify reactive oxygen species. This manganese-dependent SodA activity allows the bacteria to evade neutrophil killing mediated by calprotectin and reactive oxygen species. Thus, manganese acquisition enables S. Typhimurium to overcome host antimicrobial defenses and support its competitive growth in the intestine. PMID- 27281573 TI - Historical Y. pestis Genomes Reveal the European Black Death as the Source of Ancient and Modern Plague Pandemics. AB - Ancient DNA analysis has revealed an involvement of the bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14(th) century Black Death until the mid-18(th) century AD). Here we present reconstructed Y. pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300-1420 cal AD), Bolgar City, Russia (1362 1400 AD), and Ellwangen, Germany (1485-1627 cal AD). Our results provide support for (1) a single entry of Y. pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct. PMID- 27281574 TI - Subversion of Autophagy by Kaposi's Sarcoma-Associated Herpesvirus Impairs Oncogene-Induced Senescence. PMID- 27281575 TI - Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior. PMID- 27281576 TI - A systematic review of transcatheter aortic valve implantation via carotid artery access. AB - BACKGROUND: The carotid artery is a novel access route for transcatheter aortic valve implantation (TAVI). This may represent a viable alternative in patients unsuitable for TAVI via traditional transfemoral access, up to 20%, as well as other access routes such as subclavian, transapical and aortic. This systematic review summarises the current evidence for its safety and feasibility. METHODS: A systematic review was conducted as per the Preferred Reporting Instructions for Systematic Reviews and Meta-analysis (PRISMA) guidelines using five electronic databases. RESULTS: 16 studies were identified, including three prospective cohort studies, one retrospective cohort study, three case series and eight case reports. Data on 74 patients (mean age 76.9years) was extracted including pre operative work-up, technical procedure details and outcomes. This found 1 intraoperative death, 2 further deaths within 30days, two incidences of transient ischaemic attack, no incidences of stroke, myocardial infarction, carotid access site complications or infection, 1 patient required new dialysis and 1 patient had an intraoperative dissection which resolved. Follow-up from 30days to 1year showed symptomatic improvement and echocardiographic improvement in line with those seen in transfemoral TAVI. CONCLUSIONS: The available data on TAVI via carotid access demonstrate technical feasibility with comparable outcomes to other traditional access routes. A low number of patients, heterogeneous clinical endpoints and relatively short follow-up periods limit formal meta-analysis and firmer conclusions. For patients in which other access routes are impossible, TAVI via carotid access represents a viable and potentially crucial alternative in patients who might otherwise be untreatable. PMID- 27281577 TI - Relation between fractional flow reserve value of coronary lesions with deferred revascularization and cardiovascular outcomes in non-diabetic and diabetic patients. AB - BACKGROUND: FFR of deferred PCI lesions can predict future cardiovascular events. However, the prognostic utility of FFR remains unclear in diabetic patients in view of the potential impact of the diffuse nature of vascular disease process. We aimed to study the relation between fractional flow reserve (FFR) values and long-term outcomes of diabetic and non-diabetic patients with deferred percutaneous coronary intervention (PCI). METHODS: Patients with FFR assessment and deferred PCI (n=630) were enrolled and stratified according to diabetes mellitus (DM) status and FFR values. Patients were followed over a median of 39months. Cox proportional hazard regression models were used to analyze the association between clinical endpoints and clinical factors such as DM and FFR. RESULTS: In non-diabetics (n=450), higher FFR values were associated with less cardiovascular events (hazard ratio (HR) for death and myocardial infarction (MI) [95% confidence interval (CI)], 0.61[0.44 to 0.86] per 0.1 increase in FFR, p=0.007; HR for revascularization [95%CI], 0.66[0.49 to 0.9] per 0.1 increase in FFR, p=0.006). In diabetics (n=180), there was no difference in death and MI across the range of FFR values. Among those patients with an FFR >0.85, diabetics had a more than two-fold higher risk of death and MI than non-diabetics (HR [95% CI], 2.20 [1.19 to 4.01], p=0.015). CONCLUSION: Among non-diabetic patients with deferred PCI, a higher FFR was associated with lower rates of death, MI and revascularization. On the contrary in diabetic patients with deferred revascularization, FFR was not able to differentiate the risk of cardiovascular events. PMID- 27281578 TI - Rapid quantification of a cleavable antibody-conjugated drug by liquid chromatography/tandem mass spectrometry with microwave-assisted enzymatic cleavage. AB - Antibody-drug conjugates (ADCs) play an increasingly important role for targeted cancer treatment. One class of ADCs has attracted particular interest in drug development. These ADCs employ a cleavable chemistry linkage for drugs and utilize the reduced interchain disulfide cysteine residues for conjugation. In this work, a novel bioanalytical method for the quantification of a cleavable antibody-conjugated drug in plasma was developed, qualified, and implemented. This novel method significantly improves throughput by combining a microwave assisted, enzymatic cleavage of conjugated drugs from ADCs with a 96-well based sample preparation procedure to immunocapture ADCs in plasma. The released drug is subsequently quantified using a LC/MS/MS method. Our results represent a high throughput, generic, and sensitive quantification method for antibody-conjugated microtubule inhibitors (such as MMAE) for preclinical PK/PD studies. The linear range of the standard curve for antibody conjugated drug (MMAE) was from 2.01 to 2010ng/mL with an excellent linearity (r(2)>0.997). The intra-run precision was below 8.14% and accuracy was from -7.71% to -1.08%. No matrix effect or carryover was observed for this method. This method was successfully used to measure the level of conjugated drug in a preclinical PK/PD study in mice. PMID- 27281579 TI - Quantification and handling of nonlinearity in Raman micro-spectrometry of pharmaceuticals. AB - This work demonstrates how nonlinearity in Raman spectrometry of pharmaceuticals can be handled and accurate quantification can be achieved by applying certain chemometric methods including variable selection. Such approach proved to be successful even if the component spectra are very similar or spectral intensities of the constituents are strongly different. The relevant examples are: blends of two crystalline forms of carvedilol ("CRYST-PM" blend) and a three-component pharmaceutical model system ("PHARM-TM" blend). The widely used classical least squares regression (CLS) and partial least squares regression (PLS) quantification methods provided relatively poor root mean squared error of prediction (RMSEP) values: approximately 2-4% and 4-10% for CRYST-PM and PHARM-TM respectively. The residual plots of these models indicated the nonlinearity of the preprocessed data sets. More accurate quantitative results could be achieved with properly applied variable selection methods. It was observed that variable selection methods discarded the most intensive bands while less intensive ones were retained as the most informative spectral ranges. As a result not only the accuracy of concentration determination was enhanced, but the linearity of models was improved as well. This indicated that nonlinearity occurred especially at the intensive spectral bands. Other methods developed for handling nonlinearity were also capable of adapting to the spectral nature of both data sets. The RMSEP could be decreased this way to 1% in CRYST-PM and 3-6% in PHARM-TM. Raman maps with accurate real concentrations could be prepared this way. All quantitative models were compared by the non-parametric sum of ranking differences (SRD) method, which also proved that models based on variable selection or nonlinear methods provide better quantification. PMID- 27281580 TI - Development and full validation of an UPLC-MS/MS method for the quantification of the plant-derived alkaloid indirubin in rat plasma. AB - An UPLC-MS/MS method for the quantification of indirubin in lithium heparinized rat plasma was developed and validated according to current international guidelines. Indirubin was extracted from rat plasma by using Waters OstroTM pass through sample preparation plates. The method was validated with a LLOQ of 5.00ng/mL and an ULOQ of 500ng/mL. The calibration curve was fitted by least square quadratic regression, and a weighting factor of 1/X was applied. Recoveries of indirubin and I.S. were consistent and >=75.5%. Stability studies demonstrated that indirubin was stable in lithium heparinized rat plasma for at least 3 freeze/thaw cycles, for 3h at RT, for 96h in the autosampler at 10 degrees C, and for 84days when stored below -65 degrees C. Preliminary pharmacokinetic (PK) data were obtained from Sprague Dawley rats after intravenous administration of indirubin (2mg/kg b.w.) and blood sampling up to 12h after injection. PK parameters were determined by non-compartmental analysis. Indirubin had a half-life (t1/2) of 35min, and a relatively high clearance (CL) of 2.71L/h/kg. PMID- 27281581 TI - Isolation and characterization of related substances in alogliptin benzoate by LC QTOF mass spectrometric techniques. AB - A highly specific and efficient LC-QTOF mass spectrometric method was developed for the separation and characterization of process related substances and the major degradation products in alogliptin benzoate and its tablets. The separation was performed on Phenomenex Gemini-NX C18 column (250mm*4.6mm, 5MUm) using 0.2% formic acid-0.2% ammonium acetate in water as mobile phase A, acetonitrile and methanol (60:40, v/v) as mobile phase B in linear gradient elution mode. Forced degradation studies were also conducted under ICH prescribed stress conditions. Alogliptin benzoate and its tablets were tending to degrade under acid, alkaline, oxidative and thermal stresses, while relatively stable to photolytic stress. A total of seven related substances were detected and characterized through liquid chromatography-high resolution QTOF mass spectrometry techniques, including process related substances and degradation products, and two of them were further synthesized and characterized by NMR spectroscopy. Based on the related substances elucidation and the plausible formation mechanisms, efficient approaches were proposed to reduce or eliminate related substances, and in consequence the quality of alogliptin benzoate and its tablets have been promoted obviously. Therefore, the impurity profiles obtained are critical to the quality control and manufacturing processes optimization and monitoring of alogliptin benzoate and its tablets. PMID- 27281582 TI - Validation of UHPLC-MS/MS methods for the determination of kaempferol and its metabolite 4-hydroxyphenyl acetic acid, and application to in vitro blood-brain barrier and intestinal drug permeability studies. AB - Sedative and anxiolytic-like properties of flavonoids such as kaempferol and quercetin, and of some of their intestinal metabolites, have been demonstrated in pharmacological studies. However, routes of administration were shown to be critical for observing in vivo activity. Therefore, the ability to cross intestinal and blood-brain barriers was assessed in cell-based models for kaempferol (KMF), and for the major intestinal metabolite of KMF, 4 hydroxyphenylacetic acid (4-HPAA). Intestinal transport studies were performed with Caco-2 cells, and blood-brain barrier transport studies with an immortalized monoculture human model and a primary triple-co-culture rat model. UHPLC-MS/MS methods for KMF and 4-HPAA in Ringer-HEPES buffer and in Hank's balanced salt solution were validated according to industry guidelines. For all methods, calibration curves were fitted by least-squares quadratic regression with 1/X(2) as weighing factor, and mean coefficients of determination (R(2)) were >0.99. Data obtained with all barrier models showed high intestinal and blood-brain barrier permeation of KMF, and no permeability of 4-HPAA, when compared to barrier integrity markers. PMID- 27281583 TI - Efficient Removal of Cationic and Anionic Radioactive Pollutants from Water Using Hydrotalcite-Based Getters. AB - Hydrotalcite (HT)-based materials are usually applied to capture anionic pollutants in aqueous solutions. Generally considered anion exchangers, their ability to capture radioactive cations is rarely exploited. In the present work, we explored the ability of pristine and calcined HT getters to effectively capture radioactive cations (Sr(2+) and Ba(2+)) which can be securely stabilized at the getter surface. It is found that calcined HT outperforms its pristine counterpart in cation removal ability. Meanwhile, a novel anion removal mechanism targeting radioactive I(-) is demonstrated. This approach involves HT surface modification with silver species, namely, Ag2CO3 nanoparticles, which can attach firmly on HT surface by forming coherent interface. This HT-based anion getter can be further used to capture I(-) in aqueous solution. The observed I(-) uptake mechanism is distinctly different from the widely reported ion exchange mechanism of HT and much more efficient. As a result of the high local concentrations of precipitants on the getters, radioactive ions in water can be readily immobilized onto the getter surface by forming precipitates. The secured ionic pollutants can be subsequently removed from water by filtration or sedimentation for safe disposal. Overall, these stable, inexpensive getters are the materials of choice for removal of trace ionic pollutants from bulk radioactive liquids, especially during episodic environmental crisis. PMID- 27281584 TI - Indirect coculture of stem cells with fetal chondrons using PCL electrospun nanofiber scaffolds. AB - In vitro coculture system provides a powerful tool for tissue engineering. In this study, we evaluated the gene expressions of human adipose-derived stem cells (ASCs) on polycaprolactone (PCL) scaffold in coculture model with fetal chondrons. Electrospun PCL scaffolds (900 nm fiber diameter) were created and human infrapatellar fat pad-adipose-derived stem cells (IPFP-ASCs) were seeded on these scaffolds. Scanning electron microscopy (SEM) showed attachment of human IPFP-ASCs to scaffold. IPFP-ASCs on scaffolds were cocultured with fetal chondrons in transwell. Gene expressions were investigated using real-time polymerase chain reaction (real-time PCR). In comparison with control group, the expression level of collagen type 2 and aggrecan were significantly decreased but Indian Hedgehog(IHH) significantly increased (P < 0.05).These findings may interpreted that IPFP-ASCs seeded on PCL scaffold, in cocultures with fetal chondrons are tending toward osteogenesis rather than chondrogenesis. PMID- 27281585 TI - Too many men die young. PMID- 27281586 TI - Providing a lifeline for nurses. PMID- 27281588 TI - Erratum. PMID- 27281587 TI - A collaborative approach to reduce healthcare-associated infections. AB - Healthcare-associated infections (HAIs) continue to be an ongoing issue for patients in acute hospital settings. Effectively preventing and controlling HAIs requires a collaborative approach compelling all healthcare staff to take up responsibilities and be involved. A surgical ward in an acute hospital aimed to implement comprehensive HAI prevention strategies by applying both Kotter's eight step change model and the practice development principles into its current system. The project motivated staff to be involved and engaged in the assessment, implementation and evaluation of the project processes, and take ownership of the practice change. It focused on ensuring a clean environment, improving hand hygiene compliance, increasing staff's knowledge base regarding HAIs and enhancing active surveillance. The project achieved success in the reduction and prevention of HAIs as well as the development of a sustainable workplace culture. PMID- 27281589 TI - The role the nurse in the management of norovirus: vigilance and prevention. PMID- 27281590 TI - Infection Prevention and Control Award. Runner up 2016. PMID- 27281591 TI - Dermatology Nurse of the Year. Runner up 2016. PMID- 27281592 TI - Emollients and ageing skin: optimising effectiveness and safety. PMID- 27281593 TI - Knowledge of palliative care and attitudes towards nursing the dying patient. AB - AIMS: This study examines the palliative care knowledge and attitudes towards caring for the dying patient of nurses working in care of older people settings in one rural region in Ireland. DESIGN: A cross-sectional survey design was used combining two questionnaires: the palliative care quiz for nurses (PCQN) and the thanatophobia scale (TS). RESULTS: A total of 61 nurses completed the questionnaire. There was a significant correlation found between level of knowledge and attitudes towards palliative care (p=0.007), highlighting that as participants' level of palliative care knowledge increased, attitudes become more positive. While palliative care training did not impact on the mean overall scores, there was a significant difference in the PCQN scores of those who had completed the European Certificate in Essential Palliative Care (ECEPC) compared with those who had attended information sessions within their unit. Furthermore, increasing years as a registered nurse improved palliative care knowledge and attitudes towards caring for the dying. CONCLUSION: Nurses who completed the ECEPC had better knowledge of palliative care when compared with nurses who had not undertaken the programme. This article also considers areas of focus for palliative care training. PMID- 27281594 TI - Point-of-care testing of activated clotting time in the ICU: is it relevant? AB - BACKGROUND: Over the past 50 years there have been significant advances in both the clinical techniques and equipment used in the intensive care environment. One traditionally used point-of-care test is activated clotting time (ACT), a coagulation test primarily used during cardiopulmonary bypass surgery to monitor the anticoagulation effects of heparin. The ACT test has since emerged into the intensive care environment to guide clinical assessment and management of haemostasis in postoperative cardiac patients. OBJECTIVES: The aim of this integrative systematic review was to critique the available research evaluating the effectiveness of ACT point-of-care testing in the intensive care unit for adult patients following cardiopulmonary bypass and cardiac surgery and any impacts this may have on nursing care. METHODS: A systematic search of Medline, CINAHL and PubMed was undertaken. RESULTS: The search identified five research papers reporting on the use of ACT point-of-care testing in the intensive care unit for adult cardiac surgical patients. Meta-analysis was not performed due to the lack of homogeneity between the papers included. CONCLUSIONS: There was a lack of clear evidence for the use of the ACT point-of-care test after cardiac surgery in the intensive care environment. This review has highlighted that conventional laboratory tests are generally more accurate and reliable than this point-of-care test in guiding nursing care management. PMID- 27281596 TI - Experiences of nurse handover. PMID- 27281595 TI - The first national clinical audit for rheumatoid arthritis. AB - The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first 3 months of follow-up activity from first presentation to a rheumatology service. Access to care, management of early rheumatoid arthritis and support for self care were measured against National Institute for Health and Care Excellence quality standards; impact of early arthritis and experience of care were measured using patient-reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient-reported outcomes within 3 months and high levels of overall satisfaction were reported but these results were affected by low response rates. This article presents a summary of the national data from the audit and discusses the implications for nursing practice. PMID- 27281597 TI - A US perspective on bullying in nursing. PMID- 27281598 TI - Scrubbing up: my first experience as a student nurse in the operating theatre. PMID- 27281599 TI - Handwriting and a nurse's duty of care. PMID- 27281600 TI - Is the sexual health of children and young people adequately protected? PMID- 27281601 TI - The urgent need to improve patient complaint handling in the NHS. PMID- 27281602 TI - From staff nurse to nurse consultant. Clinical leadership part 3: developing your leadership style. PMID- 27281603 TI - Doing more to protect whistleblowers. PMID- 27281604 TI - Determination of Nanogram Microparticles from Explosives after Real Open-Air Explosions by Confocal Raman Microscopy. AB - Explosives are increasingly being used for terrorist attacks to cause devastating explosions. The detection of their postblast residues after an explosion is a high challenge, which has been barely investigated, particularly using spectroscopic techniques. In this research, a novel methodology using confocal Raman microscopy has been developed for the analysis of postblast residues from 10 open-air explosions caused by 10 different explosives (TNT, RDX, PETN, TATP, HMTD, dynamite, black powder, ANFO, chloratite, and ammonal) commonly used in improvised explosive devices. The methodology for the determination of postblast particles from explosives consisted of examining the samples surfaces with both the naked eye, first, and microscopically (10* and 50*), immediately afterward; and finally, analyzing the selected residues by confocal Raman spectroscopy in order to identify the postblast particles from explosives. Interestingly, confocal Raman microscopy has demonstrated to be highly suitable to rapidly, selectively, and noninvasively analyze postblast microscopic particles from explosives up to the nanogram range. PMID- 27281605 TI - An Electronic Cigarette Vaping Machine for the Characterization of Aerosol Delivery and Composition. AB - Introduction: Characterization of aerosols generated by electronic cigarettes (e cigarettes) is one method used to evaluate the safety of e-cigarettes. While some researchers have modified smoking machines for e-cigarette aerosol generation, these machines are either not readily available, not automated for e-cigarette testing or have not been adequately described. The objective of this study was to build an e-cigarette vaping machine that can be used to test, under standard conditions, e-liquid aerosolization and nicotine and toxicant delivery. Methods: The vaping machine was assembled from commercially available parts, including a puff controller, vacuum pump, power supply, switch to control current flow to the atomizer, three-way value to direct air flow to the atomizer, and three gas dispersion tubes for aerosol trapping. To validate and illustrate its use, the variation in aerosol generation was assessed within and between KangerTech Mini ProTank 3 clearomizers, and the effect of voltage on aerosolization and toxic aldehyde generation were assessed. Results: When using one ProTank 3 clearomizer and different e-liquid flavors, the coefficient of variation (CV) of aerosol generated ranged between 11.5% and 19.3%. The variation in aerosol generated between ProTank 3 clearomizers with different e-liquid flavors and voltage settings ranged between 8.3% and 16.3% CV. Aerosol generation increased linearly at 3-6V across e-liquids and clearomizer brands. Acetaldehyde, acrolein, and formaldehyde generation increased markedly at voltages at or above 5V. Conclusion: The vaping machine that we describe reproducibly aerosolizes e liquids from e-cigarette atomizers under controlled conditions and is useful for testing of nicotine and toxicant delivery. Implications: This study describes an electronic cigarette vaping machine that was assembled from commercially available parts. The vaping machine can be replicated by researchers and used under standard conditions to generate e-cigarette aerosols and characterize nicotine and toxicant delivery. PMID- 27281606 TI - Impact of Total Vending Machine Restrictions on US Young Adult Smoking. AB - INTRODUCTION: In an analysis of smoking using a longitudinal sample of US young adults, we extend research on tobacco vending machine restrictions beyond its prior focus on minors by examining the influence of total vending machine restrictions, which apply to adult-only facilities and represents the only remaining vending machine exemption since the enactment of the Family Smoking Prevention and Tobacco Control Act. We identify whether the passage of a restriction influences an individual's smoking on repeated observations, and if the propensity is lower among those who live in locations with a restriction. METHODS: Combining a repository of US tobacco policies at all geographic levels with the nationally-representative geocoded National Longitudinal Survey of Youth 1997 and Census data, we use multilevel logistic regression to examine the impact of total vending machine restrictions on any past 30-day smoking and past 30-day smoking of one pack per day among young adults (ages 19-31), while accounting for other tobacco control policy, community, and individual covariates. RESULTS: We find that total vending machine restrictions decrease any recent smoking (OR = 0.451; p < .01), net of other covariates. Though the passage of a restriction does not alter an individual's smoking over time, living longer in an area that has a restriction lowers the propensity that an individual will smoke at all (OR = 0.442; p < .05). We find no effect of total vending machine restrictions on smoking a pack daily. CONCLUSIONS: Total vending machine restrictions appear to be an effective, yet highly underutilized, means of tobacco control. IMPLICATIONS: Past scientific inquiries examining vending machine restrictions have focused upon minor access, adolescent perceptions of availability, and subsequent smoking. The potential for total vending machine restrictions, which extend to adult-only facilities, to influence patterns of smoking among those of legal age, remains significant. Those who are subject to total vending machine restrictions for longer periods are less likely to have recently smoked, but individuals do not change their smoking behavior in response to the passage of a restriction. These restrictions do not affect heavy smokers. Such policies are an effective but underutilized policy mechanism to prevent smoking among young adults. PMID- 27281607 TI - 3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering. AB - The ability to print defined patterns of cells and extracellular-matrix components in three dimensions has enabled the engineering of simple biological tissues; however, bioprinting functional solid organs is beyond the capabilities of current biofabrication technologies. An alternative approach would be to bioprint the developmental precursor to an adult organ, using this engineered rudiment as a template for subsequent organogenesis in vivo. This study demonstrates that developmentally inspired hypertrophic cartilage templates can be engineered in vitro using stem cells within a supporting gamma-irradiated alginate bioink incorporating Arg-Gly-Asp adhesion peptides. Furthermore, these soft tissue templates can be reinforced with a network of printed polycaprolactone fibers, resulting in a ~350 fold increase in construct compressive modulus providing the necessary stiffness to implant such immature cartilaginous rudiments into load bearing locations. As a proof-of-principal, multiple-tool biofabrication is used to engineer a mechanically reinforced cartilaginous template mimicking the geometry of a vertebral body, which in vivo supported the development of a vascularized bone organ containing trabecular-like endochondral bone with a supporting marrow structure. Such developmental engineering approaches could be applied to the biofabrication of other solid organs by bioprinting precursors that have the capacity to mature into their adult counterparts over time in vivo. PMID- 27281608 TI - LTBP2 is a prognostic marker in head and neck squamous cell carcinoma. AB - Latent transforming growth factor (TGF)-beta binding protein 2 (LTBP2) belongs to the fibrillin/LTBP extracellular matrix glycoprotein superfamily. It plays vital roles in tumorigenesis through regulating TGFbeta activity, elastogenesis and maintenance of the extracellular matrix (ECM) structure. In this study, we determined the expression levels of LTBP2 mRNA and protein in head and neck squamous cell carcinoma (HNSCC) tissues and adjacent normal tissues by quantitative reverse transcription PCR (qRT-PCR) and tissue microarray immunohistochemistry analysis (TMA-IHC) respectively. LTBP2 protein levels in cancer tissues were correlated with HNSCC patients' clinical characteristics and overall survival. Both LTBP2 mRNA and protein levels were significantly higher in HNSCC tissues than in adjacent normal tissues. High LTBP2 protein level was associated with lymph node metastasis and higher pTNM stages. High LTBP2 protein level is an independent prognostic marker in HNSCC. Our data suggest that LTBP2 acts as an oncogene in HNSCC development and progression. Detection of LTBP2 expression could be a useful prognosis marker and targeting LTBP2 may represent a novel strategy for cancer treatment through regulating activities of TGFbeta. PMID- 27281609 TI - Wnt-beta-catenin pathway signals metastasis-associated tumor cell phenotypes in triple negative breast cancers. AB - Tumor cells acquire metastasis-associated (MA) phenotypes following genetic alterations in them which cause deregulation of different signaling pathways. Earlier, we reported that an upregulation of the Wnt-beta-catenin pathway (WP) is one of the genetic salient features of triple-negative breast cancer (TNBC), and WP signaling is associated with metastasis in TNBC. Using cBioPortal, here we found that collective % of alteration(s) in WP genes, CTNNB1, APC and DVL1 among breast-invasive-carcinomas was 21% as compared to 56% in PAM50 Basal. To understand the functional relevance of WP in the biology of heterogeneous/metastasizing TNBC cells, we undertook this comprehensive study using 15 cell lines in which we examined the role of WP in the context of integrin-dependent MA-phenotypes. Directional movement of tumor cells was observed by confocal immunofluorescence microscopy and quantitative confocal video-microscopy while matrigel-invasion was studied by MMP7-specific casein zymography. WntC59, XAV939, sulindac sulfide and beta-catenin siRNA (1) inhibited fibronectin-directed migration, (2) decreased podia-parameters and motility descriptors, (3) altered filamentous-actin, (4) decreased matrigel-invasion and (5) inhibited cell proliferation as well as 3D clonogenic growth. Sulindac sulfide and beta-catenin siRNA decreased beta-catenin/active-beta-catenin and MMP7. LWnt3ACM-stimulated proliferation, clonogenicity, fibronectin-directed migration and matrigel-invasion were perturbed by WP-modulators, sulindac sulfide and GDC-0941. We studied a direct involvement of WP in metastasis by stimulating brain-metastasis-specific MDA-MB231BR cells to demonstrate that LWnt3ACM stimulated proliferation, clonogenicity and migration were blocked following sulindac sulfide, GDC-0941 and beta-catenin knockdown. We present the first evidence showing a direct functional relationship between WP activation and integrin-dependent MA-phenotypes. By proving the functional relationship between WP activation and MA-phenotypes, our data mechanistically explains (1) why different components of WP are upregulated in TNBC, (2) how WP activation is associated with metastasis and (3) how integrin-dependent MA-phenotypes can be regulated by mitigating the WP. PMID- 27281610 TI - Epigenetic modifications promote the expression of the orphan nuclear receptor NR0B1 in human lung adenocarcinoma cells. AB - The ectopic activation of NR0B1 is involved in the development of some cancers. However, the regulatory mechanisms controlling NR0B1 expression are not well understood. Therefore, the epigenetic modifications promoting NR0B1 activation were examined in this study. NR0B1 protein was detected in cancerous tissues of more than 50% of human lung adenocarcinoma (ADCA) cases and tended to be expressed in low-differentiated cancerous tissues obtained from males. Nevertheless, NR0B1 activation in ADCA has not previously been correlated with DNA demethylation. NR0B1 expression was not detected in 293T cells, although it contains a hypomethylated NR0B1 promoter. Treating 293T cells with a histone deacetylase inhibitor increased acetylated histone H4 binding to the NR0B1 promoter and activated NR0B1 expression. In contrast, treatment with histone methylase inhibitors decreased the methylation of histones H3K9 and H3K27 and slightly induced NR0B1 transcription. Furthermore, the level of acetyl-histone H4 binding to the NR0B1 promoter increased, whereas the occupancy of H3K27me3 was lower in cancerous tissues than in non-cancerous tissues. Similar histone occupancies were confirmed in a comparison of cancerous tissues with strong, moderate and negative NR0B1 expression. In conclusion, this study shows that CpG methylation within the NR0B1 promoter is not involved in the in vivo regulation of NR0B1 expression, whereas the hyperacetylation of histone H4 and the unmethylation of histones H3K9 and H3K27, and their binding to the NR0B1 promoter results in decondensed euchromatin for NR0B1 activation. PMID- 27281611 TI - Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests. AB - The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells. PMID- 27281612 TI - Phosphorylation of Notch1 by Pim kinases promotes oncogenic signaling in breast and prostate cancer cells. AB - Tumorigenesis is a multistep process involving co-operation between several deregulated oncoproteins. In this study, we unravel previously unrecognized interactions and crosstalk between Pim kinases and the Notch signaling pathway, with implications for both breast and prostate cancer. We identify Notch1 and Notch3, but not Notch2, as novel Pim substrates and demonstrate that for Notch1, the serine residue 2152 is phosphorylated by all three Pim family kinases. This target site is located in the second nuclear localization sequence (NLS) of the Notch1 intracellular domain (N1ICD), and is shown to be important for both nuclear localization and transcriptional activity of N1ICD. Phosphorylation dependent stimulation of Notch1 signaling promotes migration of prostate cancer cells, balances glucose metabolism in breast cancer cells, and supports in vivo growth of both types of cancer cells on chick embryo chorioallantoic membranes. Furthermore, Pim-induced growth of orthotopic prostate xenografts in mice is associated with enhanced nuclear Notch1 activity. Finally, simultaneous inhibition of Pim and Notch abrogates the cellular responses more efficiently than individual treatments, opening up new vistas for combinatorial cancer therapy. PMID- 27281613 TI - Human HLA-A*02:01/CHM1+ allo-restricted T cell receptor transgenic CD8+ T cells specifically inhibit Ewing sarcoma growth in vitro and in vivo. AB - The endochondral bone protein Chondromodulin-I (CHM1) provides oncogene addiction in Ewing sarcoma (ES). We pre-clinically tested the targetability of CHM1 by TCR transgenic, allo-restricted, peptide specific T cells to treat ES. We previously generated allo-restricted wildtype CD8+ T cells directed against the ES specific antigen CHM1319 causing specific responses against ES. However, utilization of these cells in current therapy protocols is hampered due to high complexity in production, relatively low cell numbers, and rapid T cell exhaustion.In order to provide off-the-shelf products in the future, we successfully generated HLA A*02:01-restricted T cell receptor (TCR) transgenic T cells directed against CHM1319 by retroviral transduction.After short-term expansion a 100% purified CHM1319-TCR-transgenic T cell population expressed a CD62L+/CD45RO and CD62L+/CD45RA+ phenotype. These cells displayed specific in vitro IFNg and granzyme B release in co-culture with HLA-A*02:01+ ES cell lines expressing CHM1. When co-injected with ES cells in Rag2-/-ELc-/- mice, CHM1-specific TCR transgenic T cells significantly inhibited the formation of lung and liver metastases in contrast to control mice. Lungs and livers of representative mice displayed CD8+ T cell infiltration in the presence (control group treated with unspecific T cells) and in the absence (study group) of metastatic disease, respectively. Furthermore, mice receiving unspecific T cells showed signs of graft-versus-host-disease in contrast to all mice, receiving CHM1319-TCR transgenic T cells.CHM1319 specific TCR-transgenic T cells were successfully generated causing anti-ES responses in vitro and in vivo. In the future, CHM1319 TCR-transgenic T cells may control minimal residual disease rendering donor lymphocyte infusions more efficacious and less toxic. PMID- 27281614 TI - A novel anticancer agent SNG1153 inhibits growth of lung cancer stem/progenitor cells. AB - Lung cancer is the leading cause of cancer-related death in both men and women. Lung cancer contains a small population of cancer cells with stem-like features known as cancer stem cells (CSCs). CSCs are often more resistant to current therapeutic treatments. Thus, it is urgent to develop a novel agent that is able to inhibit CSCs growth. In this study, we examined the ability of SNG1153, a novel chemical agent to inhibit the growth of lung CSCs. We found that SNG1153 inhibited growth and induced apoptosis in established lung cancer cells. We also found that SNG1153 inhibited the tumorsphere formation and decreased CD133 positive (lung CSC marker) cancer cells. SNG1153 was able to attenuate tumor formation in NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice injected with lung tumorsphere cells. We further demonstrated that SNG1153 induced beta-catenin phosphorylation and down-regulated beta-catenin. Our results thus demonstrate that SNG1153 effectively inhibits the growth of lung CSCs and suggest that SNG1153 may be a novel therapeutic agent to treat human lung cancer. PMID- 27281615 TI - MicroRNA-181a suppresses parkin-mediated mitophagy and sensitizes neuroblastoma cells to mitochondrial uncoupler-induced apoptosis. AB - Damage to mitochondria often results in the activation of both mitophagy and mitochondrial apoptosis. The elimination of dysfunctional mitochondria is necessary for mitochondrial quality maintenance and efficient energy supply. Here we report that miR-181a is a novel inhibitor of mitophagy. miR-181a is downregulated by mitochondrial uncouplers in human neuroblastoma SH-SY5Y cells. Overexpression of miR-181a inhibits mitochondrial uncoupling agents-induced mitophagy by inhibiting the degradation of mitochondrial proteins without affecting global autophagy. Knock down of endogenous miR-181a accelerates the autophagic degradation of damaged mitochondria. miR-181a directly targets Parkin E3 ubiquitin ligase and partially blocks the colocalization of mitochondria and autophagosomes/lysosomes. Re-expression of exogenous Parkin restores the inhibitory effect of miR-181a on mitophagy. Furthermore, miR-181a increases the sensitivity of neuroblastoma cells to mitochondrial uncoupler-induced apoptosis, whereas miR-181a antagomir prevents cell death. Because mitophagy defects are associated with a variety of human disorders, these findings indicate an important link between microRNA and Parkin-mediated mitophagy and highlights a potential therapeutic strategy for human diseases. PMID- 27281616 TI - CHES-1-like, the ortholog of a non-obstructive azoospermia-associated gene, blocks germline stem cell differentiation by upregulating Dpp expression in Drosophila testis. AB - Azoospermia is a high risk factor for testicular germ cell tumors, whose underlying molecular mechanisms remain unknown. In a genome-wide association study to identify novel loci associated with human non-obstructive azoospermia (NOA), we uncovered a single nucleotide polymorphism (rs1887102, P=2.60 *10-7) in a human gene FOXN3. FOXN3 is an evolutionarily conserved gene. We used Drosophila melanogaster as a model system to test whether CHES-1-like, the Drosophila FOXN3 ortholog, is required for male fertility. CHES-1-like knockout flies are viable and fertile, and show no defects in spermatogenesis. However, ectopic expression of CHES-1-like in germ cells significantly reduced male fertility. With CHES-1 like overexpression, spermatogonia fail to differentiate after four rounds of mitotic division, but continue to divide to form tumor like structures. In these testes, expression levels of differentiation factor, Bam, were reduced, but the expression region of Bam was expanded. Further reduced Bam expression in CHES-1 like expressing testes exhibited enhanced tumor-like structure formation. The expression of daughters against dpp (dad), a downstream gene of dpp signaling, was upregulated by CHES-1-like expression in testes. We found that CHES-1-like could directly bind to the dpp promoter. We propose a model that CHES-1-like overexpression in germ cells activates dpp expression, inhibits spermatocyte differentiation, and finally leads to germ cell tumors. PMID- 27281617 TI - Prevention of pancreatic cancer in a hamster model by cAMP decrease. AB - Smoking and alcoholism are risk factors for the development of pancreatitis associated pancreatic ductal adenocarcinoma (PDAC). We have previously shown that these cancers overexpressed stress neurotransmitters and cyclic adenosine monophosphate (cAMP) while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) was suppressed. Using a hamster model, the current study has tested the hypothesis that cAMP decrease by GABA supplementation in the drinking water prevents the development of pancreatitis-associated PDAC. Our data reveal strong preventive effects of GABA supplementation on the development of PDAC and pancreatic intraductal neoplasia (PanIN). ELISA assays and immunohistochemistry revealed significant decreases in the levels of cAMP and interleukin 6 accompanied by reductions in the expression of several cancer stem cell markers and phosphorylated signaling proteins, which stimulate cell proliferation, and migration in pancreatic exocrine cells of GABA treated animals. We conclude that cAMP decrease by GABA supplementation inhibits multiple cancer stimulating pathways in cancer stem cells, differentiated cancer cells and the immune system, identifying this approach as promising novel tool for the prevention of PDAC in individuals with a history of smoking and alcoholism. PMID- 27281622 TI - The Permanent. PMID- 27281618 TI - Immunoproteomic identification of MbovP579, a promising diagnostic biomarker for serological detection of Mycoplasma bovis infection. AB - A lack of knowledge regarding the antigenic properties of Mycoplasma bovis proteins prevents the effective control of bovine infections using immunological approaches. In this study, we detected and characterized a specific and sensitive M. bovis diagnostic biomarker. After M. bovis total proteins and membrane fractions were separated with two dimensional gel electrophoresis, proteins reacting with antiserawere detected using MALDI-TOF MS. Thirty-nine proteins were identified, 32 of which were previously unreported. Among them, immunoinformatics predicted eight antigens, encoded by Mbov_0106, 0116, 0126, 0212, 0275, 0579, 0739, and 0789, to have high immunological value. These genes were expressed in E. coli after mutagenesis of UGA to UGG using overlap extension PCR. A lipoprotein, MbovP579, encoded by a functionally unknown gene, was a sensitive and specific antigen for detection of antibodies in sera from both M. bovis infected and vaccinated cattle. The specificity of MbovP579 was confirmed by its lack of cross-reactivity with other mycoplasmas, including Mycoplasma agalactiae. An iELISA based on rMbovP579 detected seroconversion 7 days post-infection (dpi). The ELISA had sensitivity of 90.2% (95% CI: 83.7%, 94.3%) and a specificity of 97.8% (95% CI: 88.7%, 99.6%) with clinical samples. Additional comparative studies showed that both diagnostic and analytic sensitivities of the ELISA were higher than those of a commercially available kit (p<0.01). We have thus detected and characterized the novel antigen, MbovP579, and established an rMbovP579-based ELISA as a highly sensitive and specific method for the early diagnosis of M. bovis infection. PMID- 27281623 TI - Multiple Causes of Cardiotoxic Effects in Patients With Chronic Myeloid Leukemia. PMID- 27281619 TI - MiR-422a promotes loco-regional recurrence by targeting NT5E/CD73 in head and neck squamous cell carcinoma. AB - At the time of diagnosis, 60% of patients with head and neck squamous cell carcinoma (HNSCC) present tumors in an advanced stage (III-IV) of disease and 80% will relapse within the first two years post-treatment, due to their frequent radio(chemo)resistance. To identify new molecular targets and companion biomarkers, we have investigated the miRNome of 75 stage III-IV oropharynx tumors without relapse (R) or with loco-regional relapse (non-responder, NR) within two years post-treatment. Interestingly, miR-422a was significantly downregulated in NR tumors, in agreement with the increase in cell proliferation and adhesion induced by miR-422a inhibition in vitro. Furthermore, we identified CD73/NT5E oncogene as target of miR-422a. Indeed, modulation of the endogenous level of miR 422a inversely influences the expression and the enzymatic activity of CD73. Moreover, knocking down CD73 mimics the effects of miR-422a upregulation. Importantly, in tumors, miR-422a and CD73 expression levels are inversely correlated, and both are predictive of relapse free survival - especially considering loco(regional) recurrence - in vitro two independent cohorts of advanced oropharynx or HNSCC (N=255) tumors. In all, we reported, for the first time, that MiR-422a and its target CD73 are involved in early loco(regional) recurrence of HNSCC tumors and are new targets for personalized medicine. PMID- 27281624 TI - Women at a Disadvantage in Fluorouracil Treatment. PMID- 27281625 TI - Multiple Causes of Cardiotoxic Effects in Patients With Chronic Myeloid Leukemia Reply. PMID- 27281626 TI - Women at a Disadvantage in Fluorouracil Treatment-Reply. PMID- 27281627 TI - Cachexia in Radiotherapy-Treated Patients With Head and Neck Cancer: A Phenomenon That Should Be Investigated. PMID- 27281628 TI - Cachexia in Radiotherapy-Treated Patients With Head and Neck Cancer-Reply. PMID- 27281629 TI - Against "Healthy Paternalism" at the End of Life. PMID- 27281630 TI - Against "Healthy Paternalism" at the End of Life-Reply. PMID- 27281631 TI - Notes from the Field: Intoxication and Deaths Associated with Ingestion of a Racing Fuel and Carbonated Soft Drink Mixture - Tennessee, January 2016. AB - In January 2016, the Tennessee Poison Center and Tennessee Department of Health learned of the deaths of two adolescents, and the nonfatal intoxication of two other adolescents, after ingestion of a mixture of racing fuel (approximately 100% methanol) and a carbonated soft drink. The Tennessee Department of Health reviewed medical records and police reports to learn more about the racing fuel source, assess ongoing risk, and guide prevention efforts. These are the first reported deaths in the United States associated with ingestion of this racing fuel mixture. PMID- 27281632 TI - Inhibitory effect of cyanide on wastewater nitrification determined using SOUR and RNA-based gene-specific assays. AB - The effect of cyanide (CN(-) ) on nitrification was examined with samples from nitrifying bacterial enrichments using two different approaches: by measuring substrate (ammonia) specific oxygen uptake rates (SOUR), and by using RT-qPCR to quantify the transcripts of functional genes involved in nitrification. The nitrifying bioreactor was operated as a continuous reactor with a 24 h hydraulic retention time. The samples were exposed in batch vessels to cyanide for a period of 12 h. The concentrations of CN(-) used in the batch assays were 0.03, 0.06, 0.1 and 1.0 mg l(-1) . There was considerable decrease in SOUR with increasing dosages of CN(-) . A decrease of more than 50% in nitrification activity was observed at 0.1 mg l(-1) CN(-) . Based on the RT-qPCR data, there was notable reduction in the transcript levels of amoA and hao for increasing CN(-) dosage, which corresponded well with the ammonia oxidation activity measured via SOUR. The inhibitory effect of cyanide may be attributed to the affinity of cyanide to bind ferric haeme proteins, which disrupt protein structure and function. The correspondence between the relative expression of functional genes and SOUR shown in this study demonstrates the efficacy of RNA-based function-specific assays for better understanding of the effect of toxic compounds on nitrification activity in wastewater. SIGNIFICANCE AND IMPACT OF THE STUDY: The effect of cyanide on nitrifying bacteria was characterized by measuring physiological and transcriptional response. Cyanide was inhibitory to nitrification at concentrations that may be found in industrial waste. The RNA-based function specific assays represent a mechanistic approach for better understanding the effect of toxic compounds on nitrification activity in wastewater. Moreover, the relative abundance of RNA transcripts can be used to closely track in situ nitrifying bacterial activity which can be used to predict inhibition events, thereby providing a metric to potentially improve performance of wastewater nitrifying systems. PMID- 27281633 TI - A portion of plant airborne communication is endorsed by uptake and metabolism of volatile organic compounds. AB - Plants have the ability to sense volatile organic compounds (VOCs) so as to efficiently adapt to their environment. The mechanisms underlying such plant 'olfactory' systems are largely unknown. Here I would like to propose that the metabolism of VOCs in plant tissues is one of the mechanisms by which plants sense VOCs. During the gas-exchange that is essential for photosynthesis, VOCs in the atmosphere are taken into the intercellular spaces of leaves. Each VOC is partitioned between the gas phase (intercellular space) and liquid phase (cell wall) at a certain ratio determined by Henry's law. The VOCs in the cell wall diffuse through the plasma membrane to the cytosol depending on their oil/water partition coefficients. Plants detoxify some VOCs, especially those that are oxidized, through glycosylation, glutathionylation, and reduction. These metabolic processes lower the concentration of VOCs in the cytosol, which facilitates further cytosolic uptake. As a result, vigorous metabolism of VOCs in the cytosol can lead to a substantial accumulation of VOC metabolites and the depletion of glutathione or NADPH. One such metabolite (a VOC glycoside) is known to mount a direct defense against herbivores, whilst deprivation of glutathione and NADPH can fortify plants with responses similar to the oxidative stress response. PMID- 27281637 TI - Workplace Exposures and Cognitive Function During Adulthood: Evidence From National Survey of Midlife Development and the O*NET. AB - OBJECTIVE: Expand understanding of the role of selected workplace exposures (ie, occupational complexity, conflict in the workplace, pace of work, and physical hazards) in adults' cognitive function. METHODS: Cross-sectional data (n = 1991) from the second wave of the Midlife in the United States (MIDUS) study; restricted to participants who completed telephone-based cognitive assessments of episodic memory, executive functioning, and self-perceived memory. Occupational exposure data were harvested from the ONET Release 6.0. RESULTS: Greater complexity was associated with better self-perceived memory among women and men, and better episodic memory and executive functioning among women. Greater physical hazards were independently associated with poorer episodic memory and executive functioning. CONCLUSIONS: Objective assessments of physical and psychosocial exposures in the workplace are independently associated with cognitive outcomes in adulthood, with psychosocial exposures being particularly pronounced among women. PMID- 27281638 TI - Long-Term Cost-Effectiveness and Return-on-Investment of a Mindfulness-Based Worksite Intervention: Results of a Randomized Controlled Trial. AB - OBJECTIVES: The aim of this study was to conduct a cost-effectiveness and return on-investment analysis comparing a mindfulness-based worksite intervention to usual practice. METHODS: Two hundred fifty-seven governmental research institute employees were randomized to the intervention or control group. Intervention group participants received an eight-week mindfulness training, e-coaching, and supporting elements. Outcomes included work engagement, general vitality, job satisfaction, work ability, and costs. Cost-effectiveness analyses were conducted from the societal and employer's perspective, and a return-on-investment analysis from the employer's perspective. RESULTS: After 12 months, a significant but not clinically relevant adverse effect on work engagement was found (-0.19; 95% confidence interval: -0.38 to -0.01). There were no significant differences in job satisfaction, general vitality, work ability, and total costs. Probabilities of cost-effectiveness were low (<=0.25) and the intervention did not have a positive financial return to the employer. CONCLUSION: The intervention was neither cost-saving nor cost-effective. Poor e-coaching compliance might partly explain this result. PMID- 27281639 TI - Workplace Accommodations for Pregnant Employees: Associations With Women's Access to Health Insurance Coverage After Childbirth. AB - OBJECTIVE: This study evaluates the associations between workplace accommodations for pregnancy, including paid and unpaid maternity leave, and changes in women's health insurance coverage postpartum. METHODS: Secondary analysis using Listening to Mothers III, a national survey of women ages 18 to 45 years who gave birth in U.S. hospitals during 2011 to 2012 (N = 700). RESULTS: Compared with women without access to paid maternity leave, women with access to paid leave were 0.4 times as likely to lose private health insurance coverage, 0.3 times as likely to lose public health coverage, and 0.3 times as likely to become uninsured after giving birth. CONCLUSION: Workplace accommodations for pregnant employees are associated with health insurance coverage via work continuity postpartum. Expanding protections for employees during pregnancy and after childbirth may help reduce employee turnover, loss of health insurance coverage, and discontinuity of care. PMID- 27281640 TI - What Factors Are Associated With Occupational Health Office Staffing, Job Stress, and Job Satisfaction? AB - OBJECTIVE: This study sought to identify factors associated with occupational health staffing in health care settings, provide benchmarking data, and investigate relationships between staffing and worker stress and satisfaction. METHODS: Members of the Association of Occupational Health Professionals in Healthcare were sent an online survey. Data on facility served, staffing, job attitudes, and work stress were collected and analyzed. RESULTS: Number and types of personnel served were the largest predictors of staffing, accounting for 38 and 41% of the variability seen, respectively. Number of personnel served was related to worker stress and lack of work/life balance. CONCLUSION: Offices that required a provider presence had roughly one provider, seven nurses, and three clerical staff per 8000 personnel served. Occupational health workers are generally highly satisfied, and staffing has little relation to sources of job stress and satisfaction. PMID- 27281641 TI - A Validation Method to Determine Missing Years of Birth in a Cohort Study of Shipyard Workers Using Social Security Number. AB - OBJECTIVE: The objective of the study is to evaluate the generalizability and feasibility of a prediction method developed by Block et al (1983) to estimate missing age of workers by using their Social Security Numbers (SSNs). METHODS: Our study used a retrospective occupational cohort of about 15,000 workers from the Long Beach Naval Shipyard (1978 to 1985). RESULTS: Our results showed an 89.2% agreement (P < 0.0001) between the predicted and observed years of birth using Block's method. The correlation increased to 93.1% (P < 0.0001) after our modifications by removing workers with SSNs issued in U.S. territories. The method performed better in shipyard workers who obtained their SSNs after 1950. CONCLUSION: Although the method is useful in imputing missing age, the accuracy is dependent on the year, age, and location of SSN issuance. PMID- 27281642 TI - Then and Now Reactive Airways Dysfunction Syndrome. PMID- 27281646 TI - Error in Figure Key. PMID- 27281645 TI - Impact of a Comprehensive Workplace Hand Hygiene Program on Employer Health Care Insurance Claims and Costs, Absenteeism, and Employee Perceptions and Practices. AB - OBJECTIVE: The aim of this study was to determine the efficacy of a multimodal hand hygiene intervention program in reducing health care insurance claims for hygiene preventable infections (eg, cold and influenza), absenteeism, and subjective impact on employees. METHODS: A 13.5-month prospective, randomized cluster controlled trial was executed with alcohol-based hand sanitizer in strategic workplace locations and personal use (intervention group) and brief hand hygiene education (both groups). Four years of retrospective data were collected for all participants. RESULTS: Hygiene-preventable health care claims were significantly reduced in the intervention group by over 20% (P < 0.05). Absenteeism was positively impacted overall for the intervention group. Employee survey data showed significant improvements in hand hygiene behavior and perception of company concern for employee well-being. CONCLUSION: Providing a comprehensive, targeted, yet simple to execute hand hygiene program significantly reduced the incidence of health care claims and increased employee workplace satisfaction. PMID- 27281647 TI - Methylation-assisted bisulfite sequencing to simultaneously map 5fC and 5caC on a genome-wide scale for DNA demethylation analysis. AB - Active DNA demethylation is mediated by ten-eleven translocation (TET) proteins that progressively oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). We have developed a methylation-assisted bisulfite sequencing (MAB-seq) method that enables direct genome-scale mapping and quantification of 5fC and 5caC marks together at single base resolution. In bisulfite sequencing (BS), unmethylated cytosine residues (Cs), 5fCs and 5caCs, are converted to uracil and cannot be discriminated from each other. The pretreatment of the DNA with the CpG methylation enzyme M.SssI, which converts only the Cs to 5mCs, protects Cs but not 5fCs and 5caCs, which enables direct detection of 5fCs and 5caCs as uracils. Here we also describe an adapted version of the protocol to perform reduced-representation MAB-seq (RRMAB seq) that provides increased coverage on CpG-rich regions, thus reducing the execution costs and increasing the feasibility of the technique. The main advantage of MAB-seq is to reduce the number of chemical/enzymatic DNA treatments required before bisulfite treatment and to avoid the need for prohibitive sequencing coverage, thus making it more reliable and affordable than subtractive approaches. The method presented here is the ideal tool for studying DNA demethylation dynamics in any biological system. Overall timing is ~3 d for library preparation. PMID- 27281648 TI - Isolation, culture and characterization of primary mouse RPE cells. AB - Mouse models are powerful tools for the study of ocular diseases. Alterations in the morphology and function of the retinal pigment epithelium (RPE) are common features shared by many ocular disorders. We report a detailed protocol to collect, seed, culture and characterize RPE cells from mice. We describe a reproducible method that we previously developed to collect and culture murine RPE cells on Transwells as functional polarized monolayers. The collection of RPE cells takes ~3 h, and the cultures mimic in vivo RPE cell features within 1 week. This protocol also describes methods to characterize the cells on Transwells within 1-2 weeks by transmission and scanning electron microscopy (TEM and SEM, respectively), immunostaining of vibratome sections and flat mounts, and measurement of transepithelial electrical resistance. The RPE cell cultures are suitable to study the biology of the RPE from wild-type and genetically modified strains of mice between the ages of 10 d and 12 months. The RPE cells can also be manipulated to investigate molecular mechanisms underlying the RPE pathology in the numerous mouse models of ocular disorders. Furthermore, modeling the RPE pathology in vitro represents a new approach to testing drugs that will help accelerate the development of therapies for vision-threatening disorders such as macular degeneration (MD). PMID- 27281649 TI - Synthesis of a highly HOCl-selective fluorescent probe and its use for imaging HOCl in cells and organisms. AB - During infection, nicotinamide adenine dinucleotide phosphate-oxidase of innate immune cells generates important microbicidal reactive oxygen species (ROS) such as hypochlorous acid (HOCl) to kill the invading pathogens. However, excess amounts of HOCl induce oxidative damage of functional biomolecules such as DNA and proteins, which may cause chronic inflammatory diseases. Herein, we outline protocols for the preparation of a rhodamine-based HOCl probe, as well as applications thereof, with which to detect HOCl in living cells and organisms. The probe (R19S) can be prepared from a commercially available rhodamine, rhodamine 6G, in two steps. When R19S is treated with HOCl, the sulfur atom is replaced by an oxygen atom, resulting in opening of the lactone ring; thus, nonfluorescent R19S is converted to highly fluorescent rhodamine 19 (R19). R19S exhibits high selectivity for HOCl over other ROS and high sensitivity in a weakly acidic environment. In addition, we describe fluorescence imaging assays of HOCl in mouse neutrophils and Drosophila targeted using this probe. The approximate amount of time required to synthesize the probe is 2-3 d, after which it can be used for up to 5 h in the bioimaging of living cells. PMID- 27281651 TI - A Light-Induced Vinylogous Nazarov-Type Cyclization. AB - The first examples of a photochemically induced vinylogous Nazarov-type cyclization forming a cycloheptadienone core are described. The reaction can be included in a three-step cascade consisting of a photochemical isoxazole-azirine ring contraction, cobalt(II)-catalyzed ring expansion, and the photochemical cyclization. Furthermore, the first representative of the hitherto unknown 1 azatricyclo[2.2.0.0(2,6)]hexanes has been identified as a side product of the azirine formation. PMID- 27281650 TI - Nonadherence to Medications for Chronic Conditions and Nonadherence to Adjuvant Hormonal Therapy in Women With Breast Cancer. AB - Importance: While adjuvant hormonal therapy (HT) reduces mortality for women with nonmetastatic breast cancer, nonadherence to HT is common. Objective: We investigated the association between patterns of prior nonadherence to medications for chronic conditions with HT nonadherence. Design, Setting, and Participants: For this retrospective cohort study, the MarketScan database was scanned for women 18 years and older who had been diagnosed with nonmetastatic breast cancer between January 1, 2010, and December 31, 2012, and who filled 2 or more prescriptions for tamoxifen and/or an aromatase inhibitor. Main Exposures and Outcomes: Nonadherence to medications for 6 chronic conditions (hypertension, hyperlipidemia, gastroesophageal reflux disease, thyroid disease, diabetes, osteoporosis) in the 12 months before diagnosis was defined as a medication possession ratio (MPR) less than 80%. Nonadherence to HT was defined as an MPR less than 80% between the first and last prescription for HT up to 2 years. Analysis: Multivariable logistic regression was used to determine the association between prior medication nonadherence and HT nonadherence. Results: Of 21 255 women treated with adjuvant HT, 3314 (15.6%) were nonadherent, and age (<55 or >=75 years vs 55-64 years), higher 30-day out-of-pocket costs, and increased comorbidities were associated with nonadherence. Women without prior medications for 1 of the chronic conditions (n = 7828 [37%]) had an 18.4% nonadherence rate to HT. Those who used 1 or more medication prior to HT and were adherent (n = 9223 [43%]) had a 9.8% nonadherence rate to HT (relative to those without prior medications: odds ratio [OR] 0.56; 95% CI, 0.50-0.61), while those who were nonadherent to their chronic medications (n = 4214 [20%]) had a 23.1% nonadherence rate to HT (OR 1.43; 95% CI, 1.30-1.58). Adherence and nonadherence for medications for each of the 6 medical conditions was associated with adherence or nonadherence for HT, respectively. Conclusions and Relevance: We found that nonadherence to medications for chronic conditions prior to HT was associated with greater nonadherence to oral HT in patients with breast cancer. Medication nonadherence history may play an important role in determining patients at risk for nonadherence to a subsequent medication for a different illness, such as HT, and a potential target for future interventions. PMID- 27281652 TI - Metal-catalyzed oxidation of 2-alkenals generates genotoxic 4-oxo-2-alkenals during lipid peroxidation. AB - Lipid peroxidation products react with cellular molecules, such as DNA bases, to form covalent adducts, which are associated with aging and disease processes. Since lipid peroxidation is a complex process and occurs in multiple stages, there might be yet unknown reaction pathways. Here, we analyzed comprehensively 2'-deoxyguanosine (dG) adducts with oxidized arachidonic acid using liquid chromatography-tandem mass spectrometry and found the formation of 7-(2-oxo hexyl)-etheno-dG as one of the major unidentified adducts. The formation of this adduct was reproduced in the reaction of dG with 2-octenal and predominantly with 4-oxo-2-octenal (OOE). We also found that other 2-alkenals (with five or more carbons) generate corresponding 4-oxo-2-alkenal-type adducts. Importantly, it was found that transition metals enhanced the oxidation of C4-position of 2-octenal, leading to the formation of OOE-dG adduct. These findings demonstrated a new pathway for the formation of 4-oxo-2-alkenals during lipid peroxidation and might provide a mechanism for metal-catalyzed genotoxicity. PMID- 27281653 TI - A novel approach to detect test-seeking behaviour in the blood donor population: making the invisible visible. AB - BACKGROUND AND OBJECTIVES: Individuals may donate blood in order to determine their infection status after exposure to an increased infection risk. Such test seeking behaviour decreases transfusion safety. Instances of test seeking are difficult to substantiate as donors are unlikely to admit to such behaviour. However, manifestation in a population of repeat donors may be determined using statistical inference. MATERIALS AND METHODS: Test-seeking donors would be highly motivated to donate following infection risk, influencing the timing of their donation. Donation intervals within 2005-2014 of all Dutch blood donors who acquired syphilis (N = 50), HIV (N = 13), HTLV (N = 4) or HCV (N = 2) were compared to donation intervals of uninfected blood donors (N = 7 327 836) using the Anderson-Darling test. We adjusted for length bias as well as for age, gender and donation type of the infected. Additionally, the power of the proposed method was investigated by simulation. RESULTS: Among the Dutch donors who acquired infection, we found only a non-significant overrepresentation of short donation intervals (P = 0.54). However, we show by simulation that both relatively short and long donation intervals among infected donors can reveal test seeking. The power of the method is >90% if among 69 infected donors >35 (51%) are test seeking, or if among 320 infected donors >90 (30%) are test seeking. CONCLUSION: We show how statistical analysis may be used to reveal the extent of test seeking in repeat blood donor populations. In the Dutch setting, indications for test seeking behaviour were not statistically significant. This may, however, be due to the low number of infected individuals. PMID- 27281654 TI - Fortification of staple foods with zinc for improving zinc status and other health outcomes in the general population. AB - BACKGROUND: Zinc deficiency is a global nutritional problem, particularly in children and women residing in settings where diets are cereal based and monotonous. It has several negative health consequences. Fortification of staple foods with zinc may be an effective strategy for preventing zinc deficiency and improving zinc-related health outcomes. OBJECTIVES: To evaluate the beneficial and adverse effects of fortification of staple foods with zinc on health-related outcomes and biomarkers of zinc status in the general population. SEARCH METHODS: We searched the following databases in April 2015: Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3 of 12, 2015, the Cochrane Library), MEDLINE & MEDLINE In Process (OVID) (1950 to 8 April 2015), EMBASE (OVID) (1974 to 8 April 2015), CINAHL (1982 to April 2015), Web of Science (1900 to 9 April 2015), BIOSIS (1969 to 9 April 2015), POPLINE (1970 to April 2015), AGRICOLA, OpenGrey, BiblioMap, and Trials Register of Promoting Health Interventions (TRoPHI), besides regional databases (April 2015) and theses. We also searched clinical trial registries (17 March 2015) and contacted relevant organisations (May 2014) in order to identify ongoing and unpublished studies. SELECTION CRITERIA: We included randomised controlled trials, randomised either at the level of the individual or cluster. We also included non-randomised trials at the level of the individual if there was a concurrent comparison group. We included non-randomised cluster trials and controlled before-after studies only if there were at least two intervention sites and two control sites. Interventions included fortification (central/industrial) of staple foods (cereal flours, edible fats, sugar, condiments, seasonings, milk and beverages) with zinc for a minimum period of two weeks. Participants were members of the general population who were over two years of age (including pregnant and lactating women) from any country. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of studies for inclusion, extracted data from included studies, and assessed the risk of bias of the included studies. MAIN RESULTS: We included eight trials (709 participants); seven were from middle-income countries of Asia, Africa, Europe, and Latin America where zinc deficiency is likely to be a public health problem. Four trials compared the effect of zinc-fortified staple foods with unfortified foods (comparison 1), and four compared zinc-fortified staple foods in combination with other nutrients/factors with the same foods containing other nutrients or factors without zinc (comparison 2). The interventions lasted between one and nine months. We categorised most trials as having unclear or high risk of bias for randomisation, but low risk of bias for blinding and attrition. None of the studies in comparison 1 reported data on zinc deficiency.Foods fortified with zinc increased the serum or plasma zinc levels in comparison to foods without added zinc (mean difference (MD) 2.12 umol/L, 95% confidence interval (CI) 1.25 to 3.00 umol/L; 3 studies; 158 participants; low-quality evidence). Participants consuming foods fortified with zinc versus participants consuming the same food without zinc had similar risk of underweight (average risk ratio 3.10, 95% CI 0.52 to 18.38; 2 studies; 397 participants; low-quality evidence) and stunting (risk ratio (RR) 0.88, 95% CI 0.36 to 2.13; 2 studies; 397 participants; low-quality evidence). A single trial of addition of zinc to iron in wheat flour did not find a reduction in proportion of zinc deficiency (RR 0.17, 95% CI 0.01 to 3.94; very low-quality evidence). We did not find a difference in serum or plasma zinc levels in participants consuming foods fortified with zinc plus other micronutrients when compared with participants consuming the same foods with micronutrients but no added zinc (MD 0.03 umol/L, 95% CI -0.67 to 0.72 umol/L; 4 studies; 250 participants; low-quality evidence). No trial in comparison 2 provided information about underweight or stunting.There was no reported adverse effect of fortification of foods with zinc on indicators of iron or copper status. AUTHORS' CONCLUSIONS: Fortification of foods with zinc may improve the serum zinc status of populations if zinc is the only micronutrient used for fortification. If zinc is added to food in combination with other micronutrients, it may make little or no difference to the serum zinc status. Effects of fortification of foods with zinc on other outcomes including zinc deficiency, children's growth, cognition, work capacity of adults, or on haematological indicators are unknown. Given the small number of trials and participants in each trial, further investigation of these outcomes is required. PMID- 27281655 TI - Precision Chain-Walking Polymerization of trans-4-Octene Catalyzed by alpha Diimine Nickel(II) Catalysts Bearing ortho-sec-Phenethyl Groups. AB - alpha-Diimine nickel complexes bearing bulky ortho-sec-phenethyl groups (bis{[N,N'-(4-methyl-2,6-di-sec-phenethylphenyl)imino]-1,2 dimethylethane}dibromonickel (1), bis{[N,N'-(4,6-dimethyl-2-sec phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel (2), bis{[N,N'-(4-methyl 2-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel (3)) and {bis[N,N' (2,4,6-trimethylphenyl)imino]-1,2-dimethylethane}dibromidonickel (4) are used as a precatalyst for the polymerization of trans-4-octene upon activation with modified methylaluminoxane. These catalysts conduct chain-walking polymerization of trans-4-octene to give polymers possessing propyl and butyl branches with high molecular weight and narrow molecular weight distribution. The branching structure depends on the nickel complex as well as the polymerization temperature, and the ratio of propyl branch was increased with increasing the bulkiness of the ligand and decreasing the polymerization temperature. Consequently, the most bulky 1 among the complexes used is found to polymerize trans-4-octene with high 1,5-regioselectivity at -20 degrees C to give poly(1 propylpentan-1,5-diyl). PMID- 27281656 TI - National Health Promotion Policy (PNPS): chapters of a journey still under construction. PMID- 27281657 TI - Author-actors and organizational and relational processes in the review of the National Health Promotion Policy. PMID- 27281658 TI - An assessment of the National Policy on Health Promotion by SUS managers, employees, health counselors, and users. PMID- 27281659 TI - Scientific research about the National Policy for Health Promotion. PMID- 27281660 TI - Research and intervention in the promotion of health: methodological challenges of researching "with". PMID- 27281661 TI - Extended communities for action-research as a tool for the emancipatory promotion of health: conceptual and methodological bases. PMID- 27281662 TI - A mapping of 'healthy territory' initiatives, their characteristics and effectiveness. PMID- 27281663 TI - A theoretical framework on intersectoral practice in School Health Promotion. PMID- 27281664 TI - Inter-professional collaboration in the 'Health and Prevention in Schools' Project. PMID- 27281665 TI - Health promotion in professional education: challenges in Health and the need to achieve in other sectors. PMID- 27281666 TI - Health promotion policies and potential conflicts of interest involving the commercial private sector. PMID- 27281667 TI - The contribution of CEPEDOC to the development of the Brazilian Health Promotion Policy. PMID- 27281668 TI - Manguinhos, Rio de Janeiro, Brazil, "Street Clinic" team: care and health promotion practice in a vulnerable territory. PMID- 27281669 TI - The right to water and sanitation as a tool for health promotion of vulnerable groups. PMID- 27281670 TI - Perception of environmental quality of nearby localities to the Petrochemical Complex of Rio de Janeiro, Brazil. PMID- 27281671 TI - The Enlighten Campinas Program: the construction of an intersectoral and interinstitutional policy to confront violence as a social problem. PMID- 27281672 TI - Pedagogical techniques in food and nutrition groups: the backstage of choice process. PMID- 27281673 TI - Workplace Health Promotion: a path to follow. PMID- 27281674 TI - Employment and income generation as a Health Promotion Strategy: the case of women submitted to mastectomy in Nova Iguacu, RJ, Brazil. PMID- 27281675 TI - For a Global Agenda on Post Millennium Development Goals. PMID- 27281676 TI - The effect of lexical factors on recall from working memory: Generalizing the neighborhood size effect. AB - The word-length effect, the finding that lists of short words are better recalled than lists of long words, is 1 of the 4 benchmark phenomena that guided development of the phonological loop component of working memory. However, previous work has noted a confound in word-length studies: The short words used had more orthographic neighbors (valid words that can be made by changing a single letter in the target word) than long words. The confound is that words with more neighbors are better recalled than otherwise comparable words with fewer neighbors. Two experiments are reported that address criticisms of the neighborhood-size account of the word-length effect by (1) testing 2 new stimulus sets, (2) using open rather than closed pools of words, and (3) using stimuli from a language other than English. In both experiments, words from large neighborhoods were better recalled than words from small neighborhoods. The results add to the growing number of studies demonstrating the substantial contribution of long-term memory to what have traditionally been identified as working memory tasks. The data are more easily explained by models incorporating the concept of redintegration rather than by frameworks such as the phonological loop that posit decay offset by rehearsal. (PsycINFO Database Record PMID- 27281677 TI - Insight into and Computational Studies of the Selective Synthesis of 6H Dibenzo[b,h]xanthenes. AB - Starting from 2-hydroxy-1,4-naphthoquinone (lawsone), we synthesized eight new 6H dibenzo[b,h]xanthene derivatives selectively under solvent-free conditions. Spectroscopic investigations confirmed that only the isomer 6H dibenzo[b,h]xanthene was obtained in all eight cases. Computational studies provide a rationalization for the selective appearance of these isomers having as an intermediate an addition product. PMID- 27281678 TI - Improved Optimization for the Cluster Jastrow Antisymmetric Geminal Power and Tests on Triple-Bond Dissociations. AB - We present a novel specialization of the variational Monte Carlo linear method for the optimization of the recently introduced cluster Jastrow antisymmetric geminal power ansatz, achieving a lower-order polynomial cost scaling than would be possible with a naive application of the linear method and greatly improving optimization performance relative to that of the previously employed quasi-Newton approach. We test the methodology on highly multireference triple-bond stretches, achieving accuracy superior to those of the traditional coupled cluster theory and multireference perturbation theory in both the typical example of N2 and the transition-metal-oxide example of [ScO](+). PMID- 27281680 TI - Peripheral Refraction, Peripheral Eye Length, and Retinal Shape in Myopia. AB - PURPOSE: To investigate how peripheral refraction and peripheral eye length are related to retinal shape. METHODS: Relative peripheral refraction (RPR) and relative peripheral eye length (RPEL) were determined in 36 young adults (M +0.75D to -5.25D) along horizontal and vertical visual field meridians out to +/ 35 degrees and +/-30 degrees , respectively. Retinal shape was determined in terms of vertex radius of curvature Rv, asphericity Q, and equivalent radius of curvature REq using a partial coherence interferometry method involving peripheral eye lengths and model eye raytracing. Second-order polynomial fits were applied to RPR and RPEL as functions of visual field position. Linear regressions were determined for the fits' second order coefficients and for retinal shape estimates as functions of central spherical refraction. Linear regressions investigated relationships of RPR and RPEL with retinal shape estimates. RESULTS: Peripheral refraction, peripheral eye lengths, and retinal shapes were significantly affected by meridian and refraction. More positive (hyperopic) relative peripheral refraction, more negative RPELs, and steeper retinas were found along the horizontal than along the vertical meridian and in myopes than in emmetropes. RPR and RPEL, as represented by their second-order fit coefficients, correlated significantly with retinal shape represented by REq. CONCLUSIONS: Effects of meridian and refraction on RPR and RPEL patterns are consistent with effects on retinal shape. Patterns derived from one of these predict the others: more positive (hyperopic) RPR predicts more negative RPEL and steeper retinas, more negative RPEL predicts more positive relative peripheral refraction and steeper retinas, and steeper retinas derived from peripheral eye lengths predict more positive RPR. PMID- 27281681 TI - Eye Movements and Road Hazard Detection: Effects of Blur and Distractors. AB - PURPOSE: To examine the effects of optical blur, auditory distractors, and age on eye movement patterns while performing a driving hazard perception test (HPT). METHODS: Twenty young (mean age 27.1 +/- 4.6 years) and 20 older (73.3 +/- 5.7 years) drivers with normal vision completed a HPT in a repeated-measures counterbalanced design while their eye movements were recorded. Testing was performed under two visual (best-corrected vision and with +2.00DS blur) and two distractor (with and without auditory distraction) conditions. Participants were required to respond to road hazards appearing in the HPT videos of real-world driving scenes and their hazard response times were recorded. RESULTS: Blur and distractors each significantly delayed hazard response time by 0.42 and 0.76 s, respectively (p < 0.05). A significant interaction between age and distractors indicated that older drivers were more affected by distractors than young drivers (response with distractors delayed by 0.96 and 0.60 s, respectively). There were no other two- or three-way interaction effects on response time. With blur, for example, both groups fixated significantly longer on hazards before responding compared to best-corrected vision. In the presence of distractors, both groups exhibited delayed first fixation on the hazards and spent less time fixating on the hazards. There were also significant differences in eye movement characteristics between groups, where older drivers exhibited smaller saccades, delayed first fixation on hazards, and shorter fixation duration on hazards compared to the young drivers. CONCLUSIONS: Collectively, the findings of delayed hazard response times and alterations in eye movement patterns with blur and distractors provide further evidence that visual impairment and distractors are independently detrimental to driving safety given that delayed hazard response times are linked to increased crash risk. PMID- 27281679 TI - Erythropoietin either Prevents or Exacerbates Retinal Damage from Eye Trauma Depending on Treatment Timing. AB - PURPOSE: Erythropoietin (EPO) is a promising neuroprotective agent and is currently in Phase III clinical trials for the treatment of traumatic brain injury. The goal of this study was to determine if EPO is also protective in traumatic eye injury. METHODS: The left eyes of anesthetized DBA/2J or Balb/c mice were exposed to a single 26 psi overpressure air-wave while the rest of the body was shielded. DBA/2J mice were given intraperitoneal injections of EPO or buffer and analyses were performed at 3 or 7 days post-blast. Balb/c mice were given intramuscular injections of rAAV.EpoR76E or rAAV.eGFP either pre- or post blast and analyses were performed at 1 month post-blast. RESULTS: EPO had a bimodal effect on cell death, glial reactivity, and oxidative stress. All measures were increased at 3 days post-blast and decreased at 7-days post-blast. Increased retinal ferritin and NADPH oxygenases were detected in retinas from EPO treated mice. The gene therapy approach protected against axon degeneration, cell death, and oxidative stress when given after blast, but not before. CONCLUSIONS: Systemic, exogenous EPO and EPO-R76E protects the retina after trauma even when initiation of treatment is delayed by up to 3 weeks. Systemic treatment with EPO or EPO-R76E beginning before or soon after trauma may exacerbate protective effects of EPO within the retina as a result of increased iron levels from erythropoiesis and, thus, increased oxidative stress within the retina. This is likely overcome with time as a result of an increase in levels of antioxidant enzymes. Either intraocular delivery of EPO or treatment with non-erythropoietic forms of EPO may be more efficacious. PMID- 27281682 TI - Oligomer Formation of Amyloid-beta(29-42) from Its Monomers Using the Hamiltonian Replica-Permutation Molecular Dynamics Simulation. AB - Oligomers of amyloid-beta peptides (Abeta) are formed during the early stage of the amyloidogenesis process and exhibit neurotoxicity. The oligomer formation process of Abeta and even that of Abeta fragments are still poorly understood, though understanding of these processes is essential for remedying Alzheimer's disease. In order to better understand the oligomerization process of the C terminal Abeta fragment Abeta(29-42) at the atomic level, we performed the Hamiltonian replica-permutation molecular dynamics simulation with Abeta(29-42) molecules using the explicit water solvent model. We observed that oligomers increased in size through the sequential addition of monomers to the oligomer, rather than through the assembly of small oligomers. Moreover, solvent effects played an important role in this oligomerization process. PMID- 27281683 TI - Trajectory Calculations for Bergman Cyclization Predict H/D Kinetic Isotope Effects Due to Nonstatistical Dynamics in the Product. AB - An unusual H/D kinetic isotope effect (KIE) is described, in which isotopic selectivity arises primarily from nonstatistical dynamics in the product. In DFT based quasiclassical trajectories of Bergman cyclization of (Z)-3-hexen-1,5-diyne (1) at 470 K, the new CC bond retains its energy, and 28% of nascent p-benzyne recrosses back to the enediyne on a vibrational time scale. The competing process of intramolecular vibrational redistribution (IVR) in p-benzyne is too slow to prevent this. Deuteration increases the rate of IVR, which decreases the fraction of recrossing and increases the yield of statistical (trapable) p-benzyne, 2. Trapable yields for three isotopomers of 2 range from 72% to 86%. The resulting KIEs for Bergman cyclization differ substantially from KIEs predicted by transition state theory, which suggests that IVR in this reaction can be studied by conventional KIEs. Leakage of vibrational zero point energy (ZPE) into the reaction coordinate was probed by trajectories in which initial ZPE in the CH/CD stretching modes was reduced by 25%. This did not change the predicted KIEs. PMID- 27281685 TI - Subpicosecond Photoinduced Hole Transfer from a CdS Quantum Dot to a Molecular Acceptor Bound Through an Exciton-Delocalizing Ligand. AB - This paper describes the enhancement of the rate of hole transfer from a photoexcited CdS quantum dot (QD), with radius R = 2.0 nm, to a molecular acceptor, phenothiazine (PTZ), by linking the donor and acceptor through a phenyldithiocarbamate (PTC) linker, which is known to lower the confinement energy of the excitonic hole. Upon adsorption of PTC, the bandgap of the QD decreases due to delocalization of the exciton, primarily the excitonic hole, into interfacial states of mixed QD/PTC character. This delocalization enables hole transfer from the QD to PTZ in <300 fs (within the instrument response of the laser system) when linked by PTC, but not when linked by a benzoate group, which has a similar length and conjugation as PTC but does not delocalize the excitonic hole. Comparison of the two systems was aided by quantification of the surface coverage of benzoate and PTC-linked PTZ by (1)H NMR. This work provides direct spectroscopic evidence of the enhancement of the rate of hole extraction from a colloidal QD through covalent linkage of a hole acceptor through an exciton-delocalizing ligand. PMID- 27281684 TI - Redoxable heteronanocrystals functioning magnetic relaxation switch for activatable T1 and T2 dual-mode magnetic resonance imaging. AB - T1/T2 dual-mode magnetic resonance (MR) contrast agents (DMCAs) have gained much attention because of their ability to improve accuracy by providing two pieces of complementary information with one instrument. However, most of these agents are "always ON" systems that emit MR contrast regardless of their interaction with target cells or biomarkers, which may result in poor target-to-background ratios. Herein, we introduce a rationally designed magnetic relaxation switch (MGRS) for an activatable T1/T2 dual MR imaging system. Redox-responsive heteronanocrystals, consisting of a superparamagnetic Fe3O4 core and a paramagnetic Mn3O4 shell, are synthesized through seed-mediated growth and subsequently surface-modified with polysorbate 80. The Mn3O4 shell acts as both a protector of Fe3O4 in aqueous environments to attenuate T2 relaxation and as a redoxable switch that can be activated in intracellular reducing environments by glutathione. This simultaneously generates large amounts of magnetically decoupled Mn(2+) ions and allows Fe3O4 to interact with the water protons. This smart nanoplatform shows an appropriate hydrodynamic size for the EPR effect (10-100 nm) and demonstrates biocompatibility. Efficient transitions of OFF/ON dual contrast effects are observed by in vitro imaging and MR relaxivity measurements. The ability to use these materials as DMCAs is demonstrated via effective passive tumor targeting for T1- and T2-weighted MR imaging in tumor-bearing mice. PMID- 27281686 TI - Syntheses, Structures, and Electrochemistry of the Defective ccp [Pt33(CO)38](2-) and the bcc [Pt40(CO)40](6-) Molecular Nanoclusters. AB - The molecular [Pt33(CO)38](2-) nanocluster was obtained from the thermal decomposition of Na2[Pt15(CO)30] in methanol. The reaction of [Pt19(CO)22](4-) with acids (1-2 equiv) affords the unstable [Pt19(CO)22](3-) trianion, which evolves with time leading eventually to the [Pt40(CO)40](6-) hexa-anion. The total structures of both nanoclusters were determined via single-crystal X-ray diffraction. [Pt33(CO)38](2-) displays a defective ccp Pt33 core and shows that localized deformations occur in correspondence of atomic defects to "repair" them. In contrast, [Pt40(CO)40](6-) shows a bcc Pt40 core and represents the largest Pt cluster with a body-centered structure. The rich electrochemistry of the two high-nuclearity platinum carbonyl clusters was studied by cyclic voltammetry and electrochemical in situ Fourier transform infrared spectroscopy. The redox changes of [Pt33(CO)38](2-) show features of chemical reversibility and electrochemical quasi-reversibility, and the vibrational spectra in the CO stretching region of the nine redox forms of the cluster [Pt33(CO)38](n) (n = 0 to -4, -6 to -9) are reported. Almost all the redox processes exhibited by [Pt40(CO)40](6-) are chemically and electrochemically reversible, and the eight oxidation states of [Pt40(CO)40] from -4 to -11 were spectroscopically characterized. The effect of the more regular bcc Pt-carbonyl cluster structure of [Pt40(CO)40](6-) with respect to that of the defective ccp Pt33 core on the redox behavior is discussed. PMID- 27281687 TI - Wastewater-based epidemiological evaluation of the effect of air pollution on short-acting beta-agonist consumption for acute asthma treatment. AB - Asthma, one of the most common chronic diseases in the world and a leading cause of hospitalization among children, has been associated with outdoor air pollution. We applied the wastewater-based epidemiology (WBE) approach to study the association between the use of salbutamol, a short-acting beta-agonist used to treat acute bronchospasm, and air pollution in the population of Milan, Italy. Composite 24-h samples of untreated wastewater were collected daily and analyzed for human metabolic residues of salbutamol by liquid chromatography tandem mass spectrometry. Corresponding daily outdoor concentrations of particular matter up to 10um (PM10) and 2.5um (PM2.5) in aerodynamic diameter, nitrogen dioxide, ozone, sulfur dioxide, and benzene were collected from the public air monitoring network. Associations at different lag times (0-10 days) were assessed by a log linear Poisson regression model. We found significant direct associations between defined daily doses (DDD) of salbutamol and mean daily concentrations of PM10 and PM2.5 up to nine days of lag time. The highest rate ratio, and 95% confidence interval (CI), of DDD of salbutamol was 1.06 (95% CI: 1.02-1.10) and 1.07 (95% CI: 1.02-1.12) at seven days of lag time and for an increase of 10 MUg/m(3) of PM10 and PM2.5, respectively. Reducing the mean daily PM10 concentration in Milan from 50 to 30MUg/m(3) means that 852 (95% CI: 483-1504) daily doses of salbutamol per day would not be used. These results confirm the association between asthma and outdoor PM10 and PM2.5 and prove the potential of the WBE approach to quantitatively estimate the relation between environmental exposures and diseases. PMID- 27281688 TI - Association of Bisphenol A exposure and Attention-Deficit/Hyperactivity Disorder in a national sample of U.S. children. AB - BACKGROUND: Bisphenol A (BPA) has been linked to changes in the dopamine system and development of an Attention-Deficit/Hyperactivity Disorder (ADHD) phenotype in animal models, with differing effects in males compared to females. We examined the association between urinary BPA concentrations and ADHD in a national sample of U.S. children, and whether this association differs by child sex. METHODS: We used data from the 2003-2004 National Health and Nutrition Examination Survey, a cross-sectional, nationally representative sample of the U.S. POPULATION: Participants were 8-15 years of age (N=460). Using a diagnostic interview to ascertain the presence of ADHD in the past year, multivariable logistic regression examined the link between concurrent urinary BPA concentrations and ADHD status. RESULTS: Of the 460 participants, 7.1% [95% CI: 4.4-11.3] met Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) criteria for ADHD. Children who had BPA concentrations at or above the median of the sample had higher prevalence of meeting criteria for ADHD (11.2% [95% CI: 6.8-17.8]) than those with BPA concentrations below the median (2.9% [95% CI: 1.1-7.2]). Higher urinary BPA concentrations were associated with ADHD (adjusted odds ratio [aOR]: 5.68 [95% CI: 1.6-19.8] for BPA concentrations above vs. below the median). In sex-stratified analyses, these associations were stronger in boys (aOR=10.9 [95% CI: 1.4-86.0]) than in girls (aOR=2.8 [95% CI: 0.4-21.3]), although the BPA by sex interaction term was not significant (p=0.25). CONCLUSION: We found evidence that higher urinary BPA concentrations were associated with ADHD in U.S. children; these associations were stronger in boys than in girls. Considering the widespread use of BPA and growing literature on neurobehavioral effects of BPA in children, further study is warranted to determine if reducing exposure to BPA may represent an important avenue for ADHD prevention. PMID- 27281689 TI - Exposure to outdoor air pollution during trimesters of pregnancy and childhood asthma, allergic rhinitis, and eczema. AB - BACKGROUND: Mounting evidence suggests that exposure to ambient air pollution is associated with the development of childhood allergic diseases, but the effect of prenatal exposure to air pollution on the risk of childhood asthma and allergy is unclear. OBJECTIVES: We evaluated the association between maternal exposure to outdoor air pollution during different trimesters of pregnancy and incidence of asthma, allergic rhinitis, and eczema in 2598 preschool children aged 3-6 years in China. METHODS: Children's lifetime incidence of allergic diseases was obtained using questionnaire. Individual exposure to outdoor air pollutants during trimesters of pregnancy was estimated by an inverse distance weighted (IDW) method based on the measured concentrations at monitoring stations. We used multiple logistic regression method to estimate the odds ratio (OR) of asthma, allergic rhinitis, and eczema for per interquartile range (IQR) increase in the exposure to air pollutant in each trimester, which was adjusted for the effect of other air pollutants and its effect in other trimesters by a multi pollutant/trimester model. RESULTS: Incidence of asthma (6.8%), allergic rhinitis (7.3%), and eczema (28.6%) in children was associated with maternal exposure to traffic-related pollutant NO2 during entire pregnancy with OR (95% confidence interval [CI]) respectively 1.63 (0.99-2.70), 1.69 (1.03-2.77), and 1.37 (1.04 1.80). After adjustment for other pollutants and trimesters, we found the association was significant only in specific trimester: the first trimester for eczema (1.54, 1.14-2.09), the second trimester for asthma (1.72, 1.02-2.97), and the third trimester for allergic rhinitis (1.77, 1.09-2.89). Sensitivity analysis indicated that the trimester sensitive to the development of allergic diseases was stable. CONCLUSION: Maternal exposure to traffic-related air pollutant NO2 during pregnancy, especially in specific trimesters, is associated with an increased risk of developing asthma, rhinitis, and eczema in children. Our results support the hypothesis that childhood allergic diseases originate in fetal life and are triggered by traffic-related air pollution in sensitive trimesters. PMID- 27281691 TI - Specific Synergist for Neonicotinoid Insecticides: IPPA08, a cis-Neonicotinoid Compound with a Unique Oxabridged Substructure. AB - Insecticide synergists are key components to increase the control efficacy and reduce active ingredient use. Here, we describe a novel insecticide synergist with activity specific for insecticidal neonicotinoids. The synergist IPPA08, a cis configuration neonicotinoid compound with a unique oxabridged substructure, could increase the toxicity of most neonicotinoid insecticides belonging to the Insecticide Resistance Action Committee (IRAC) 4A subgroup against a range of insect species, although IPPA08 itself was almost inactive to insects at synergistic concentrations. Unfortunately, similar effects were observed on the honey bee (Apis mellifera) and the brown planthopper (Nilaparvata lugens), resistant to imidacloprid. IPPA08 did not show any effects on toxicity of insecticides with different targets, which made us define it as a neonicotinoid specific synergist. Unlike most insecticide synergists, by inhibition of activities of detoxification enzymes, IPPA08 showed no effects on enzyme activities. The results revealed that IPPA08 worked as a synergist through a distinct way. Although the modulating insect nicotinic acetylcholine receptors (nAChRs, targets of neonicotinoid insecticides) were supposed as a possible mode of action for IPPA08 as a neonicotinoid-specific synergist, direct evidence is needed in further studies. In insect pest control, IPPA08 acts as a target synergist to increase neonicotinoid toxicity and reduce the amount of neonicotinoid used. Combinations of IPPA08 and insecticidal neonicotinoids may be developed into new insecticide formulations. In summary, combining an active ingredient with a "custom" synergist appears to be a very promising approach for the development of effective new insecticide products. PMID- 27281690 TI - Residential proximity to organophosphate and carbamate pesticide use during pregnancy, poverty during childhood, and cognitive functioning in 10-year-old children. AB - BACKGROUND: Low-income communities and communities of color have been shown to experience disproportionate exposure to agricultural pesticides, which have been linked to poorer neurobehavioral outcomes in infants and children. Few studies have assessed health impacts of pesticide mixtures in the context of socioeconomic adversity. OBJECTIVES: To examine associations between residential proximity to toxicity-weighted organophosphate (OP) and carbamate pesticide use during pregnancy, household- and neighborhood-level poverty during childhood, and IQ scores in 10-year-old children. METHODS: We evaluated associations between both nearby agricultural pesticide use and poverty measures and cognitive abilities in 10-year-old children (n = 501) using data from a longitudinal birth cohort study linked with data from the California Pesticide Use Reporting system and the American Community Survey. Associations were assessed using multivariable linear regression. RESULTS: Children of mothers in the highest quartile compared to the lowest quartile of proximal pesticide use had lower performance on Full Scale IQ [beta = -3.0; 95% Confidence Interval (CI) = (-5.6, -0.3)], Perceptual Reasoning [beta = -4.0; (-7.6, -0.4)], and Working Memory [beta = -2.8; (-5.6, 0.1)]. Belonging to a household earning an income at or below the poverty threshold was associated with approximately two point lower scores on Full Scale IQ, Verbal Comprehension, and Working Memory. Living in the highest quartile of neighborhood poverty at age 10 was associated with approximately four point lower performance on Full Scale IQ, Verbal Comprehension, Perceptual Reasoning, and Working memory. CONCLUSIONS: Residential proximity to OP and carbamate pesticide use during pregnancy and both household- and neighborhood-level poverty during childhood were independently associated with poorer cognitive functioning in children at 10 years of age. PMID- 27281692 TI - Impact of a person-centred community rehabilitation service on outcomes for individuals with a neurological condition. AB - PURPOSE: To evaluate the impact of a person-centred, community rehabilitation service on outcomes for people with a neurological condition, in the first year of service. METHOD: A prospective, observational, pre-post study was conducted with 206 people who had a neurological condition and attended the rehabilitation service to restore function (e.g., Stroke); maximize recovery in an ongoing situation (e.g., Spina Bifida); or maximize function and independence while preparing for inevitable decline (e.g., Parkinson's Disease). Outcomes were measured via self-report questionnaires, prior to, and following three months of rehabilitation. The primary outcome was achievement of self-identified goals, measured by the Patient-Specific Functional scale. Secondary outcomes included the Lawton Instrumental Activities of Daily Living (IADL) scale, EQ-5D-5L European Quality of Life scale, and ICECAP-O - Index of Capability for Older Adults and health and medical resource use. RESULTS: Participants demonstrated significant goal achievement and a significant reduction in health and medical resource use. There were small positive changes in the Lawton IADL, EQ-5D-5L, and ICECAP-O however these changes were not significant. CONCLUSIONS: In the first year of operation, the community rehabilitation service made a significant impact on outcomes for individuals with a neurological condition. Further research is required to identify appropriate measures of activities of daily living and quality of life that reflect person-centred rehabilitation outcomes for restoring function, maximizing function, or preparing for functional decline. Implications for Rehabilitation Self-identified goals are an important guide for achievement of meaningful outcomes for individuals with a neurological condition. Person centred outcome measures are required to evaluate the benefits of a person centred community rehabilitation service for individuals with a neurological condition. PMID- 27281693 TI - Band Alignment and Minigaps in Monolayer MoS2-Graphene van der Waals Heterostructures. AB - Two-dimensional layered MoS2 shows great potential for nanoelectronic and optoelectronic devices due to its high photosensitivity, which is the result of its indirect to direct band gap transition when the bulk dimension is reduced to a single monolayer. Here, we present an exhaustive study of the band alignment and relativistic properties of a van der Waals heterostructure formed between single layers of MoS2 and graphene. A sharp, high-quality MoS2-graphene interface was obtained and characterized by micro-Raman spectroscopy, high-resolution X-ray photoemission spectroscopy (HRXPS), and scanning high-resolution transmission electron microscopy (STEM/HRTEM). Moreover, direct band structure determination of the MoS2/graphene van der Waals heterostructure monolayer was carried out using angle-resolved photoemission spectroscopy (ARPES), shedding light on essential features such as doping, Fermi velocity, hybridization, and band-offset of the low energy electronic dynamics found at the interface. We show that, close to the Fermi level, graphene exhibits a robust, almost perfect, gapless, and n doped Dirac cone and no significant charge transfer doping is detected from MoS2 to graphene. However, modification of the graphene band structure occurs at rather larger binding energies, as the opening of several miniband-gaps is observed. These miniband-gaps resulting from the overlay of MoS2 and the graphene layer lattice impose a superperiodic potential. PMID- 27281694 TI - Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells. AB - BACKGROUND: Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. METHODS: We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs) were determined by neutral red staining. RESULTS: The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (DeltaPsim) loss, activation of both caspase-3 and -9, increase of annexin V(+)PI(+) cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. CONCLUSIONS: Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown). Our data implicate that 2-MCA could be a potential agent for anticancer therapy. PMID- 27281695 TI - Effect of Cell Cycle Interactions and Inhibition of Histone Deacetylases on Development of Porcine Embryos Produced by Nuclear Transfer. AB - The aim of this study was to evaluate if the positive effects of inhibiting histone deacetylase enzymes on cell reprogramming and development of somatic cell nuclear transfer (SCNT) embryos is affected by the cell cycle stage of nuclear donor cells and host oocytes at the time of embryo reconstruction. SCNT embryos were produced with metaphase II (MII) or telophase II (TII) cytoplasts and nuclear donor cells that were either at the G1-0 or G2/M stages. Embryos reconstructed with the different cell cycle combinations were treated or not with the histone deacetylase inhibitor (HDACi) Scriptaid for 15 h and then cultured in vitro for 7 days. Embryos reconstructed with MII-G1-0 and TII-G2/M developed to the blastocyst stage with a higher frequency compared to the other groups, confirming the importance of cell cycle interactions on cell reprogramming and SCNT embryo development. Treatment with HDACi improved development of SCNT embryos produced with MII but not TII cytoplasts, independently of the cell cycle stage of nuclear donor cells. These findings provide evidence that the positive effect of HDACi treatment on development of SCNT embryos depends upon cell cycle interactions between the host cytoplast and the nuclear donor cells. PMID- 27281696 TI - Providers' perspectives of factors influencing implementation of evidence-based treatments in a community mental health setting: A qualitative investigation of the training-practice gap. AB - This study aims to elucidate relations between provider perceptions of aspects of the consolidated framework for implementation research (Damschroder et al., 2009) and provider attitudes toward the implementation of evidence-based treatments (EBTs) in an ethnically diverse community health setting. Guided by directed content analysis, we analyzed 28 semistructured interviews that were conducted with providers during the pre-implementation phase of a larger implementation study for cognitive processing therapy for posttraumatic stress disorder (Resick et al., 2008). Our findings extend the existing literature by also presenting provider-identified client-level factors that contribute to providers' positive and negative attitudes toward EBTs. Provider-identified client-level factors include the following: client motivation to engage in treatment, client openness to EBTs, support networks of family and friends, client use of community and government resources, the connection and relationship with their therapist, client treatment adherence, client immediate needs or crises, low literacy or illiteracy, low levels of education, client cognitive limitations, and misconceptions about therapy. These results highlight the relations between provider perceptions of their clients, provider engagement in EBT training, and subsequent adoption of EBTs. We present suggestions for future implementation research in this area. (PsycINFO Database Record PMID- 27281697 TI - Studying Muscle Protein Turnover in CKD. PMID- 27281698 TI - Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. AB - BACKGROUND AND OBJECTIVES: The high risk of cardiovascular disease (CVD) and premature death in patients with CKD associates with a plethora of elevated circulating biomarkers that may reflect distinct signaling pathways or simply, are epiphenomena of CKD. We compared the predictive strength of 12 biomarkers analyzed concomitantly in patients with stage 5 CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From 1994 to 2014, 543 patients with stage 5 CKD (median age =56 years old; 63% men; 199 patients had CVD) took part in our study on malnutrition, inflammation, and CVD in incident dialysis patients. Circulating levels of albumin, ferritin, high-sensitivity C-reactive protein (hsCRP), IGF-1, IL-6, orosomucoid, troponin T (TnT), TNF, soluble intracellular adhesion molecule, soluble vascular cellular adhesion molecule 1 (sVCAM-1), and platelet and white blood cell (WBC) counts were analyzed as predictors of the presence of clinically overt CVD at baseline, protein-energy wasting (PEW), and subsequent all-cause mortality. During follow-up for a median of 28 months, there were 149 deaths, 81 of which were caused by CVD. RESULTS: Most biomarkers were elevated compared with reference values and--except for albumin, ferritin, and IGF-1 higher in patients with CVD. In receiver operating characteristic analysis, age, IL-6, TnT, hsCRP, and IGF-1 were classifiers of baseline CVD and predictors of all-cause mortality. In addition to age, diabetes mellitus, smoking (for CVD), and PEW, only IL-6, relative risk (RR) 1.10 and 95% confidence interval ([95% CI], 1.02 to 1.19), sVCAM-1 RR 1.09 (95% CI, 1.01 to 1.17), and serum albumin RR 0.89 (95% CI, 0.83 to 0.95) associated with baseline CVD, and only WBC, hazard ratio (HR) 1.94 (95% CI, 1.34 to 2.82), IL-6 HR 1.79 (95% CI, 1.20 to 2.67), and TNF HR 0.65 (95% CI, 0.44 to 0.97) predicted all-cause mortality. CONCLUSIONS: In addition to age and comorbidities, only IL-6, sVCAM-1, and albumin could independently of other biomarkers-classify clinical CVD, and only IL-6, WBC, and TNF could-independently of other biomarkers-predict all-cause mortality risk. These data underscore the robustness of IL-6 as a classifier of clinically overt CVD and predictor of all-cause mortality in patients with stage 5 CKD. PMID- 27281699 TI - High Dose Omega-3 Fatty Acid Administration and Skeletal Muscle Protein Turnover in Maintenance Hemodialysis Patients. AB - BACKGROUND AND OBJECTIVES: Protein energy wasting and systemic inflammation are prevalent in maintenance hemodialysis (MHD) patients. Omega-3 (omega-3) fatty acids have anti-inflammatory properties and have been shown to improve protein homeostasis. We hypothesized that administration of high-dose (2.9 g/d) omega-3 would be associated with decreased muscle protein breakdown in MHD patients with systemic inflammation. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: This is a substudy from a randomized, placebo-controlled study (NCT00655525). Patients were recruited between September 2008 and June 2011. Primary inclusion criteria included signs of chronic inflammation (average C-reactive protein of >=5 mg/L over three consecutive measurements), lack of active infectious or inflammatory disease, no hospitalization within 1 month prior to the study, and not receiving steroids (>5 mg/d) and/or immunosuppressive agents. The primary outcomes were forearm muscle and whole body protein breakdown and synthesis before and after the intervention. The patients received omega-3 (n=11) versus placebo (n=9) for 12 weeks. Analysis of covariance was used to compare outcome variables at 12 weeks. Models were adjusted for a propensity score that was derived from age, sex, race, baseline high sensitivity C-reactive protein, diabetes mellitus, and fat mass because the groups were not balanced for several characteristics. RESULTS: Compared with placebo, omega-3 supplementation was significantly associated with decreased muscle protein breakdown at 12 weeks (-31, [interquartile range, -98--13] versus 26 [interquartile range, 13-87] ug/100 ml per min; P=0.01), which remained significant after multivariate adjustment (-46, [95% confidence interval, -102 to -1] ug/100 ml per min). omega-3 Supplementation resulted in decreased forearm muscle protein synthesis while the rate in the placebo group increased; however, there is no longer a statistically significant difference in skeletal muscle protein synthesis or in net protein balance after multivariate adjustment. There was no statistically significant effect of omega-3 supplementation on whole body protein synthesis or breakdown. CONCLUSIONS: High dose omega-3 supplementation over 12 weeks in MHD patients with systemic inflammation was associated with attenuation of forearm muscle protein breakdown but did not influence skeletal muscle protein synthesis, skeletal muscle net protein balance or any component of the whole-body protein balance. These results should be interpreted cautiously given the imbalance in the two groups and the short duration of the intervention. PMID- 27281701 TI - The Only Constant Is Change: Next Generation Materials and Medical Device Design for Physical and Mental Health. AB - Cell health and cell network patency dictate human physical and mental health throughout life. Cutting edge multiscale imaging and mapping of cell to organ structure and function is unravelling the remarkable plasticity of cellular networks, from bone to brain. Insights from these studies will enable the development of next generation implants to replace, repair and reprogram cellular networks, for promotion of mental and physical health. PMID- 27281700 TI - Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome. AB - BACKGROUND AND OBJECTIVES: Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport-related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. RESULTS: The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte-related genes. CONCLUSIONS: The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X-linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte-related genes. PMID- 27281702 TI - Phenotypic and Molecular Characterization of Domestic Cat (Felis catus) Spermatogonial Stem Cells. AB - In many mammalian species, surface markers have been used to obtain enriched populations of spermatogonial stem cells (SSCs) for assisted reproduction and other applications; however, little is known about the expression patterns of feline SSCs. In this study, we assessed expression of the SSC surface markers commonly used in other species, KIT, ITGA6, CD9, GFRalpha1, ADGRA3, and THY1, in addition to the less frequently used pluripotent markers TRA-1-60, TRA-1-81, SSEA 1, and SSEA-4 in SSCs of both prepubertal and adult domestic cats (Felis catus). To further characterize cat SSCs, we sorted cells using SSC-specific markers and evaluated the expression of the pluripotent transcription factors NANOG, POU5F1, and SOX2 and the proto-oncogene MYC within these populations. We concluded that SSC surface markers used in other mammalian species were not specific for identifying cat SSCs. However, the pluripotent markers we evaluated were more specific to cat spermatogonia, and the presence of SSEA-1 and SSEA-4 in fewer and primarily individual cells suggests that these two markers may be used for enrichment of cat SSCs. The expression of pluripotent transcription factors at mRNA level by single-stained cells positive for SSEA-4 and by dual-stained cells positive for both GFRalpha1 and SSEA-4 reflects the undifferentiated stage of cat SSCs. The absence of transcription factors in double-stained cells positive for only one marker implies the loss of the stem cell-like identity with the loss of either GFRalpha1 or SSEA-4. Further investigation is warranted to elucidate the biological characteristics of these spermatogonial subpopulations. PMID- 27281703 TI - Virus-Mediated Metalloproteinase 1 Induction Revealed by Transcriptome Profiling of Bovine Herpesvirus 4-Infected Bovine Endometrial Stromal Cells. AB - Viral infections can cause genital tract disorders (including abortion) in cows, and bovine herpesvirus 4 (BoHV-4) is often present in endometritis-affected animals. A major problem with cattle uterine viral infections in general, and BoHV-4 in particular, is our limited understanding of the pathogenic role(s) that these infections play in the endometrium. A similar lack of knowledge holds for the molecular mechanisms utilized, and the host cell pathways affected, by BoHV 4. To begin to fill these gaps, we set up optimized conditions for BoHV-4 infection of a pure population of bovine endometrial stromal cells (BESCs) to be used as source material for RNA sequencing-based transcriptome profiling. Many genes were found to be upregulated (417) or downregulated (181) after BoHV-4 infection. As revealed by enrichment functional analysis on differentially expressed genes, BoHV-4 infection affects various pathways related to cell proliferation and cell surface integrity, at least three of which were centered on upregulation of matrix metalloproteinase 1 (MMP1) and interleukin 8 (IL8). This was confirmed by reverse transcription PCR, real-time PCR, Western immunoblot analysis, and a luciferase assay with a bovine MMP1-specific promoter reporter construct. Further, it was found that MMP1 transcription was upregulated by the BoHV-4 transactivator IE2/RTA, leading to abnormally high metalloproteinase tissue levels, potentially leading to defective endometrium healing and unresolved inflammation. Based on these findings, we propose a new model for BoHV-4 action centered on IE2-mediated MMP1 upregulation and novel therapeutic interventions based on IFN gamma-mediated MMP1 downregulation. PMID- 27281704 TI - Quiescence Loosens Epigenetic Constraints in Bovine Somatic Cells and Improves Their Reprogramming into Totipotency. AB - Reprogramming by nuclear transfer (NT) cloning forces cells to lose their lineage specific epigenetic marks and reacquire totipotency. This process often produces molecular anomalies that compromise clone development. We hypothesized that quiescence alters the epigenetic status of somatic NT donor cells and elevates their reprogrammability. To test this idea, we compared chromatin composition and cloning efficiency of serum-starved quiescent (G0) fibroblasts versus nonstarved mitotically selected (G1) controls. We show that G0 chromatin contains reduced levels of Polycomb group proteins EED, SUZ12, PHC1, and RING2, as well as histone variant H2A.Z. Using quantitative confocal immunofluorescence microscopy and fluorometric enzyme-linked immunosorbent assay, we further show that G0 induced DNA and histone hypomethylation, specifically at H3K4me3, H3K9me2/3 and H3K27me3, but not H3K9me1. Collectively, these changes resulted in a more relaxed G0 chromatin state. Following NT, G0 donors developed into blastocysts that retained H3K9me3 hypomethylation, both in the inner cell mass and trophectoderm. G0 blastocysts from different cell types and cell lines developed significantly better into adult offspring. In conclusion, serum starvation induced epigenetic changes, specifically hypotrimethylation, that provide a mechanistic correlate for increased somatic cell reprogrammability. PMID- 27281706 TI - Initial Segment Differentiation Begins During a Critical Window and Is Dependent upon Lumicrine Factors and SRC Proto-Oncogene (SRC) in the Mouse. AB - Without a fully developed and functioning initial segment, the most proximal region of the epididymis, male infertility results. Therefore, it is important to understand the development of the initial segment. During postnatal development of the epididymis, many cellular processes of the initial segment are regulated by lumicrine factors, which are produced by the testis and enter the epididymis with testicular luminal fluid. In this report, we showed that prior to Postnatal Day 15 (P15), the initial segment was lumicrine factor independent in the mouse. However, from P19 onward, lumicrine factors were essential for the proliferation and survival of initial segment epithelial cells. Therefore, P15 to P19 was a critical window that established the dependency of lumicrine factors in the initial segment epithelium. The initial segment-specific kinase activity profile, a marker of initial segment differentiation, was also established during this window. The SFK (SRC proto-oncogene family kinases), ERK pathway (known as the RAF/MEK/ERK pathway) components, and AMPK (AMP-activated protein kinases) pathway components had increased activities from P15 to P19, suggesting that lumicrine factors regulated SFK/ERK/AMPK signaling to initiate differentiation of the initial segment from P15 to P19. Compared with litter mate controls, juvenile Src null mice displayed lower levels of MAPK3/1 (mitogen-activated protein kinase 3/1) activity and a reduced level of differentiation in the initial segment epithelium, a similar phenotype resulting from inhibition of SRC activity within the window of P15 to P19. Therefore, lumicrine factor-dependent SRC activity signaling through MAPK3/1 is important for the initiation of initial segment differentiation during a critical window of development. PMID- 27281705 TI - mTOR Regulates Gap Junction Alpha-1 Protein Trafficking in Sertoli Cells and Is Required for the Maintenance of Spermatogenesis in Mice. AB - The mammalian target of rapamycin (Mtor) gene encodes a serine/threonine kinase that acts as a master regulator of processes as diverse as cell growth, protein synthesis, cytoskeleton reorganization, and cell survival. In the testis, physiological roles for Mtor have been proposed in perinatal Sertoli cell proliferation and blood-testis barrier (BTB) remodeling during spermatogenesis, but no in vivo studies of Mtor function have been reported. Here, we used a conditional knockout approach to target Mtor in Sertoli cells. The resulting Mtor(flox/flox); Amhr2(cre/+) mice were characterized by progressive, adult-onset testicular atrophy associated with disorganization of the seminiferous epithelium, loss of Sertoli cell polarity, increased germ cell apoptosis, premature release of germ cells, decreased epididymal sperm counts, increased sperm abnormalities, and infertility. Histopathologic analysis and quantification of the expression of stage-specific markers showed a specific loss of pachytene spermatocytes and spermatids. Although the BTB and the ectoplasmic specializations did not appear to be altered in Mtor(flox/flox);Amhr2(cre/+) mice, a dramatic redistribution of gap junction alpha-1 (GJA1) was detected in their Sertoli cells. Phosphorylation of GJA1 at Ser373, which is associated with its internalization, was increased in the testes of Mtor(flox/flox); Amhr2(cre/+) mice, as was the expression and phosphorylation of AKT, which phosphorylates GJA1 at this site. Together, these results indicate that Mtor expression in Sertoli cells is required for the maintenance of spermatogenesis and the progression of germ cell development through the pachytene spermatocyte stage. One mechanism of mTOR action may be to regulate gap junction dynamics by inhibiting AKT, thereby decreasing GJA1 phosphorylation and internalization. mTOR regulates gap junction alpha-1 protein distribution in Sertoli cells and is necessary for progression through the pachytene spermatocyte stage. PMID- 27281707 TI - Unraveling the Sperm Bauplan: Relationships Between Sperm Head Morphology and Sperm Function in Rodents. AB - Rodents have spermatozoa with features not seen in other species. Sperm heads in many rodent species bear one or more apical extensions known as "hooks." The process by which hooks have evolved, together with their adaptive significance, are still controversial issues. In order to improve our understanding of the biological meaning of these sperm head adaptations, we analyzed hook curvature angles, hook length, and overall hook shape in muroid rodents by using geometric morphometrics. We also searched for relationships between hook design and measurements of intermale competition to assess whether postcopulatory sexual selection was an important selective force driving changes in this sperm structure. Finally, we sought possible links between aspects of sperm hook design and sperm velocity as a measure of sperm performance. Results showed that one hook curvature angle is under strong selective pressure. Similarly, hook length appears to be strongly selected by sexual selection, with this selective force also exhibiting a stabilizing role reducing intermale variation in this trait. The adaptive significance of changes in hook structure was supported by the finding that there are strong and significant covariations between hook dimensions and shape and between hook design and sperm swimming velocity. Overall, this study strongly suggests that postcopulatory sexual selection has an important effect on the design of the sperm head that, in turn, is important for enhancing sperm velocity, a function crucial to reaching the vicinity of the female gamete and winning fertilizations under competitive situations. PMID- 27281709 TI - Possible Contribution of Alpha2,6-Sialylation to Luteolysis in Cows by Inhibiting the Luteotropic Effects of Galectin-1. AB - The corpus luteum (CL) is essential for establishing pregnancy. If pregnancy does not occur during the estrous cycle, luteolysis is induced by prostaglandin (PG) F2alpha secreted from the uterus. Galectin-1, a beta-galactose-binding protein, is expressed in the functional CL of cows and increases the viability of bovine luteal steroidogenic cells (LSCs) by modifying the functions of membrane glycoproteins. The binding of galectin-1 to glycoproteins is blocked by alpha2,6 sialylation of the terminal galactose residues of glycoconjugates, which is catalyzed by a sialyltransferase (ST6Gal-I). However, the physiological role of alpha2,6-sialic acid in bovine CL is unclear. The level of alpha2,6-sialylation of the bovine CL was higher during the regressed-luteal stage than in other luteal stages. Lectin histochemistry revealed that alpha2,6-sialylated glycoconjugates were localized to luteal endothelial cells throughout the estrous cycle. In addition, alpha2,6-sialylated glycoconjugates concentrated to the membrane of LSCs during the regressed-luteal stage. PGF2alpha treatment for 72 h enhanced the expression of ST6Gal-I mRNA and the level of alpha2,6-sialylated glycoproteins in mid-LSCs. The level of alpha2,6-sialylated glycoproteins of late stage LSCs (Days 15-17 after ovulation) was higher than that of mid-stage LSCs (Days 8-12 after ovulation), and galectin-1 increased the viability of mid-LSCs but not that of late-stage LSCs. Furthermore, galectin-1 increased the viability of late-LSCs when alpha2,6-sialic acid residues were removed by neuraminidase. The overall findings suggest that alpha2,6-sialylation stimulated by PGF2alpha contributes to luteolysis by inhibiting the luteotropic effects of galectin-1 in bovine CL. PMID- 27281710 TI - A Men's Workplace Health Intervention: Results of the POWERPLAY Program Pilot Study. AB - OBJECTIVE: To explore physical activity and eating behaviors among men following the implementation of a gender-sensitive, workplace health promotion program. METHODS: Using a pre-post within-subjects design, computer-assisted telephone interviewing (CATI) was used to collect health-related information along with physical activity and fruit/vegetable intake at baseline and after 6 months. RESULTS: At baseline, participants (N = 139) consumed 3.58 servings of fruit and vegetables/day and engaged in an average of 229.77 min/week moderate-vigorous physical activity (MVPA). At 6 months, daily fruit/vegetable intake did not increase, whereas MVPA increased by 112.3 min/week. CONCLUSIONS: The POWERPLAY program successfully increased weekly MVPA. Engaging men in health promotion can be a challenge; here, the workplace served as a valuable environment for achieving positive change. PMID- 27281711 TI - Use of Framingham Risk Score as a Clinical Tool for the Assessment of Fitness for Work: Results From a Cohort Study. AB - OBJECTIVE: The aim of this study is to validate the use of the Framingham Risk Score (FRS) as clinical tool to predict the risk of diagnosis of unsuitability for work in a cohort of Italian workers. METHODS: A cohort of workers has been observed from January 2006 to March 2014. FRS was calculated at each visit. Health surveillance diagnosis of unsuitability for work was selected as outcome. RESULTS: Two thousand eight hundred fifty seven workers were observed, 58.9% were men, mean age was 51.6 (+/-6.7), the mean FRS was 15.1% (+/-10.7%). Increased values of FRS at baseline were associated with increased rate of diagnosis of unsuitability for work (Hazard ratio [HR], 11.2, 95%CI, 3.3 to 37.8). CONCLUSIONS: FRS is a strong predictor of diagnosis of unsuitability for work and should be used as a clinical tool for the assessment of fitness for work in health surveillance. PMID- 27281708 TI - Zinc Transport Differs in Rat Spermatogenic Cell Types and Is Affected by Treatment with Cyclophosphamide. AB - Adequate zinc levels are required for proper cellular functions and for male germ cell development. Zinc transport is accomplished by two families of zinc transporters, the ZIPs and the ZnTs, that increase and decrease cytosolic zinc levels, respectively. However, very little is known about zinc transport in the testis. Furthermore, whether cytotoxic agents such as cyclophosphamide (CPA), a known male germ cell toxicant, can affect zinc transport and homeostasis is unknown. We examined zinc transporter expression and zinc transport in pachytene spermatocytes (PS) and round spermatids (RS) in a normal state and after exposure to CPA. We observed differences in the expression of members of the ZnT and ZIP families in purified populations of PS and RS. We also observed that RS accumulate more zinc over time than PS. The expression of many zinc binding genes was altered after CPA treatment. Interestingly, we found that the expression levels of ZIP5 and ZIP14 were increased in PS from animals treated daily with 6 mg/kg CPA for 4 wk but not in RS. This up-regulation led to an increase in zinc uptake in PS but not in RS from treated animals compared to controls. These data suggest that CPA treatment may alter zinc homeostasis in male germ cells leading to an increased need for zinc. Altered zinc homeostasis may disrupt proper germ cell development and contribute to infertility and effects on progeny. PMID- 27281712 TI - Clobazam higher-evening differential dosing as an add-on therapy in refractory epilepsy. AB - PURPOSE: Clobazam treatment tailored to the timing of patient's seizures may improve seizure control. We aim to describe the safety and efficacy of higher evening differential dose of clobazam as add-on therapy in patients with night time/early morning seizures. METHOD: Differential dosing with higher evening dosing was started based on a high proportion of seizures (>80%) at nighttime (6p.m. to 6a.m.). Differential dosing was defined as providing more than 50% of the total daily dose of clobazam after 6p.m. RESULTS: Twenty-seven patients were treated with clobazam differential dosing as an add-on therapy. The median age was 9.1 years, with 11 (40.7%) females and median of the first follow-up was 2.7 months. Patients with differential dosing tolerated a higher median total clobazam dose of 0.8mg/kg/d at first follow-up, as compared to 0.6mg/kg/d in controls. In differential dose, the median percentage of the total clobazam dose administered in the evening was 66.7%. Differential dose patients exhibited a median seizure reduction of 75% as compared to 50% in controls (p<0.005). Patients with generalized seizures benefited the most from differential dosing with a 77.5% median seizure reduction, as compared to 50% in controls (p=0.017). CONCLUSION: Higher-evening differential dose of clobazam improved seizure control in patients with predominantly nighttime and early-morning seizures. Chronotherapy tailored to the patients' seizure susceptibility patterns may improve care in epilepsy patients as differential dosing may allow for higher overall treatment doses at times of greatest seizure susceptibility without increased side effects at other times. PMID- 27281713 TI - Observation of Two Triplet-Pair Intermediates in Singlet Exciton Fission. AB - Singlet fission is an excitation multiplication process in molecular systems that can circumvent energy losses and significantly boost solar cell efficiencies; however, the nature of a critical intermediate that enables singlet fission and details of its evolution into multiple product excitations remain obscure. We resolve the initial sequence of events comprising the fission of a singlet exciton in solids of pentacene derivatives using femtosecond transient absorption spectroscopy. We propose a three-step model of singlet fission that includes two triplet-pair intermediates and show how transient spectroscopy can distinguish initially interacting triplet pairs from those that are spatially separated and noninteracting. We find that the interconversion of these two triplet-pair intermediates is limited by the rate of triplet transfer. These results clearly highlight the classical kinetic model of singlet fission and expose subtle details that promise to aid in resolving problems associated with triplet extraction. PMID- 27281718 TI - Automated detection and analysis of depolarization events in human cardiomyocytes using MaDEC. AB - Optical imaging-based methods for assessing the membrane electrophysiology of in vitro human cardiac cells allow for non-invasive temporal assessment of the effect of drugs and other stimuli. Automated methods for detecting and analyzing the depolarization events (DEs) in image-based data allow quantitative assessment of these different treatments. In this study, we use 2-photon microscopy of fluorescent voltage-sensitive dyes (VSDs) to capture the membrane voltage of actively beating human induced pluripotent stem cell-derived cardiomyocytes (hiPS CMs). We built a custom and freely available Matlab software, called MaDEC, to detect, quantify, and compare DEs of hiPS-CMs treated with the beta-adrenergic drugs, propranolol and isoproterenol. The efficacy of our software is quantified by comparing detection results against manual DE detection by expert analysts, and comparing DE analysis results to known drug-induced electrophysiological effects. The software accurately detected DEs with true positive rates of 98-100% and false positive rates of 1-2%, at signal-to-noise ratios (SNRs) of 5 and above. The MaDEC software was also able to distinguish control DEs from drug treated DEs both immediately as well as 10min after drug administration. PMID- 27281719 TI - Trace metals in the giant tiger prawn Penaeus monodon and mangrove sediments of the Tanzania coast: Is there a risk to marine fauna and public health? AB - Mangroves ecosystems support livelihood and economic activities of coastal communities in the tropics and subtropics. Previous reports have documented the inefficiency of waste treatment facilities in Tanzania to contain trace metals. Therefore, the rapidly expanding coastal population and industrial sector is likely to threaten mangrove ecosystems with metal pollution. This study analysed trace metals in 60 sediment samples and 160 giant tiger prawns from the Tanzanian coast in order to document the distribution of trace metals and to establish if measured levels present a threat to mangrove fauna and are of public health importance. High levels of Cr, Co, Cu, Fe, Mn, Ni, and V was observed in mangroves of river Pangani, Wami, and Rufiji. Multivariate analysis showed that they originate mainly from weathering and erosion in the river catchments. Extreme enrichment of Cd was observed in a mangrove affected by municipal sewage. The distribution of Hg, Pb, and Zn was related with urbanisation and industrial activities along the coast. The metal pollution index was high at Pangani, Saadani, and Rufiji, suggesting that these estuarine mangroves are also affected by human activities in the catchment. Moderate to considerable ecological risks were observed in all sampled mangroves, except for Kilwa Masoko. It was revealed that As, Cd, and Hg present moderate risks to fauna. High levels of Cu, Fe and Zn were observed in prawns but the level of the non-essential Cd, Hg, and Pb did not exceed the maximum allowed levels for human consumption. However, based on the trends of fish consumption in the country, weekly intake of Hg is likely to exceed provisional tolerable weekly intake level, especially in fishing communities. This calls for measures to control Hg emissions and to strengthen sewage and waste treatment in coastal cities and urban centres in the basin of major rivers. PMID- 27281720 TI - Effects of the Intraneural and Subparaneural Ultrasound-Guided Popliteal Sciatic Nerve Block: A Prospective, Randomized, Double-Blind Clinical and Electrophysiological Comparison. AB - BACKGROUND AND OBJECTIVES: This prospective, randomized, double-blind study compared the effects of the ultrasound-guided popliteal sciatic nerve block performed by either intraneural or subparaneural approach followed by an electrophysiological evaluation. We hypothesized that intraneural injection provides a faster onset with a better success rate compared with the subparaneural approach. METHODS: Eighty-eight patients were enrolled and randomized to receive an ultrasound-guided popliteal sciatic nerve block injecting 15 mL ropivacaine 1% according to an intraneural injection (group INTRA = 44) or a subparaneural injection (group SUBPARA = 44). The primary end point was the onset time of sensory and motor block, whereas secondary end points were successful, duration of the block, and the variation of the electrophysiological assessment after 5 weeks. The study was registered prior to patient enrollment (clinicaltrials.gov identifier NCT01987128). RESULTS: The median onset time for successful sciatic nerve block in the INTRA group was 10 (5-15 [5-30]) minutes versus 25 (15-35 [5-45]) minutes in the SUBPARA group (P < 0.001), with a rate of 41/43 (95.3%) compared with 25/40 (62.5%) in the SUBPARA group (P < 0.001). No difference was found regardless of the duration of the block. Fifty-three patients also performed the electrophysiological assessment at 5 weeks, showing a subclinical, significant reduction in amplitude of the action potentials with no difference between groups. No patients reported any clinical neurological complications after 6 months. CONCLUSIONS: In ultrasound-guided popliteal sciatic nerve block, intraneural injection provided a faster onset and better success rate compared with subparaneural. Both techniques resulted in a similar subclinical reduction in amplitude of the sciatic action potentials at 5 weeks after surgery. These findings should not be extended to other approaches. PMID- 27281721 TI - Radiofrequency Procedures to Relieve Chronic Knee Pain: An Evidence-Based Narrative Review. AB - BACKGROUND AND OBJECTIVES: Chronic knee pain from osteoarthritis or following arthroplasty is a common problem. A number of publications have reported analgesic success of radiofrequency (RF) procedures on nerves innervating the knee, but interpretation is hampered by lack of clarity regarding indications, clinical protocols, targets, and longevity of benefit from RF procedures. METHODS: We reviewed the following medical literature databases for publications on RF procedures on the knee joint for chronic pain: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar up to August 9, 2015. Data on scores for pain, validated scores for measuring physical disability, and adverse effects measured at any timepoint after 1 month following the interventions were collected, analyzed, and reported in this narrative review. RESULTS: Thirteen publications on ablative or pulsed RF treatments of innervation of the knee joint were identified. A high success rate of these procedures in relieving chronic pain of the knee joint was reported at 1 to 12 months after the procedures, but only 2 of the publications were randomized controlled trials. There was evidence for improvement in function and a lack of serious adverse events of RF treatments. CONCLUSIONS: Radiofrequency treatments on the knee joint (major or periarticular nerve supply or intra-articular branches) have the potential to reduce pain from osteoarthritis or persistent postarthroplasty pain. Ongoing concerns regarding the quality, procedural aspects, and monitoring of outcomes in publications on this topic remain. Randomized controlled trials of high methodological quality are required to further elaborate role of these interventions in this population. PMID- 27281722 TI - Comparison of 2-Chloroprocaine, Bupivacaine, and Lidocaine for Spinal Anesthesia in Patients Undergoing Knee Arthroscopy in an Outpatient Setting: A Double-Blind Randomized Controlled Trial. AB - BACKGROUND AND OBJECTIVES: Knee arthroscopy is a well-established procedure in day-case surgery, which is frequently performed under spinal anesthesia. It is, however, controversial whether the choice for a specific local anesthetic translates into relevant outcomes. We hypothesized that the use of 2 chloroprocaine would be associated with a faster recovery from sensorimotor block. METHODS: Ninety-nine patients were included in this prospective, double blind, randomized controlled trial and randomly allocated to receive either 40 mg 2-chloroprocaine, 40 mg lidocaine, or 7.5 mg bupivacaine. The primary endpoint was the time until complete recovery of sensory block. Secondary endpoints included time to recovery from motor block, failure rates, incidence of hypotension/bradycardia, postoperative pain, first mobilization, voiding and discharge times, and the incidence of transient neurologic symptoms. This clinical trial was registered prior to patient enrollment (EudraCT 2011-003675 11). RESULTS: Patients in the chloroprocaine group had a significantly shorter time until recovery from sensory block (median, 2.6 hours; interquartile range [IQR], 2.2-2.9 hours) than patients in the lidocaine group (3.1 hours; IQR, 2.7 3.6 hours; P < 0.006) and in the bupivacaine group (6.1 hours; IQR, 5.5 hours to undefined hours; P < 0.0001). Chloroprocaine was associated with a significantly faster recovery from motor block than lidocaine and bupivacaine. Times to first mobilization, voiding, and discharge were significantly shorter for chloroprocaine when compared with bupivacaine, but not with lidocaine. In the bupivacaine group, patients needed significantly less rescue medication for postoperative pain when compared with lidocaine and chloroprocaine. Groups did not differ with respect to patient satisfaction, incidence of bradycardia/hypotension, and transient neurologic symptom rate. CONCLUSIONS: For spinal anesthesia in patients undergoing ambulatory knee arthroscopy, chloroprocaine has the shortest time to complete recovery of sensory and motor block compared with bupivacaine and lidocaine. PMID- 27281723 TI - The Role of Spectral Tissue Sensing During Lumbar Transforaminal Epidural Injection. AB - Spectral tissue sensing (STS) exploits the scattering and absorption of light by tissue. The main objective of the present study was to determine whether STS can discriminate between correct and incorrect placement of the needle tip during lumbar transforaminal epidural injection. This was a single-blind prospective observational study in 30 patients with lumbar radicular pain scheduled for lumbar transforaminal epidural injection. Spectral tissue sensing data from the needle tip were acquired along the needle trajectory at 4 predefined measurement points and compared with ultrasound, fluoroscopy, and digital subtraction angiography images. Spectral tissue sensing data contained the full spectra. The lipid and hemoglobin content at the different measurement points was also calculated, and partial least-squares discriminant analysis was used to estimate the sensitivity and specificity of STS. Spectral tissue sensing identified correct needle placement with a sensitivity of 57% and a specificity of 82%, and intraforaminal versus extraforaminal locations were identified with a sensitivity of 80% and a specificity of 71%. PMID- 27281724 TI - In-Plane Ultrasound-Guided Lumbar Plexus Block Using Catheter-Over-Needle Technique in a 14-Month-Old Baby. AB - This case report details the feasibility of a continuous lumbar plexus block obtained with a paramedian transverse scan of the lumbar paravertebral region, using a catheter-over-needle system, as a main postoperative orthopedic analgesia, in a 14-month-old patient undergoing surgical treatment of a localized Ewing family tumor of the right proximal femur. After surgery, the patient remained in the intensive care unit for 3 days; pain was assessed regularly using the Children's and Infants' Postoperative Pain Scale, and comfort was monitored. Analgesia was provided with continuous levobupivacaine 0.2% infusion 0.2 mL kg h, rectal paracetamol 15 mg kg, and oral ibuprofen 60 mg twice per day, with a dose of morphine 0.05 mg kg intravenously as rescue. Pain relief was excellent, and no additional morphine was needed during the postoperative course. Nausea, vomiting, and disturbed sleep were not reported. Oral diet was resumed on the first postoperative day. In conclusion, this case represents successful postoperative management of orthopedic pain in a child using continuous posterior lumbar plexus infusion. PMID- 27281725 TI - Adverse Events and Resource Utilization After Spinal and General Anesthesia in Infants Undergoing Pyloromyotomy. AB - BACKGROUND AND OBJECTIVES: Interest in spinal anesthesia (SA) is increasing because of concern about the long-term effects of intravenous (IV) and inhaled anesthetics in young children. This study compared SA versus general anesthesia (GA) in infants undergoing pyloromyotomy. METHODS: Between 2000 to 2013, the University of Vermont Medical Center almost exclusively used SA for infant pyloromyotomy surgery, whereas Columbia University Medical Center relied on GA. Outcomes included adverse events (AEs) within 48 hours of surgery, operating room (OR) time, and postoperative length of stay (LOS). Regression was used to evaluate the association between anesthesia technique and outcomes, accounting for demographic and clinical covariates. RESULTS: We studied 218 infants with SA at the University of Vermont Medical Center and 206 infants with GA at Columbia University Medical Center. In the SA group, 96.3% of infants had adequate initial analgesic levels, but 35.8% required supplemental IV or inhaled anesthetic agents. Compared with GA, the risk of AEs in SA (adjusted odds ratio, 0.60; 95% confidence interval [CI], 0.27-1.36) did not significantly differ, but SA was associated with shorter OR times (17.5 minutes faster; 95% CI, 13.5-21.4 minutes) and shorter postoperative LOS (GA is 1.19 times longer; 95% CI, 1.01-1.40). CONCLUSIONS: Infants undergoing pyloromyotomy with SA had shorter OR times and postoperative LOS, no significant differences in AE rates, and decreased exposure to IV and inhaled anesthetics, although SA infants often still required supplemental anesthetics. Whether these differences result in any long-term benefit is unclear; further studies are needed to determine the risk of rare AEs, such as aspiration. PMID- 27281727 TI - Prospective, Randomized Double-Blind Study: Does Decreasing Interscalene Nerve Block Volume for Surgical Anesthesia in Ambulatory Shoulder Surgery Offer Same Day Patient Recovery Advantages? AB - BACKGROUND AND OBJECTIVES: In this randomized double-blind prospective study in patients undergoing shoulder arthroscopy, we compared the effects of ultrasound guided interscalene nerve block using 20 mL (intervention group) and 40 mL (control group) of a mepivacaine 1.5% and bupivacaine 0.5% mixture (1:1 volume) on ipsilateral handgrip strength and other postoperative end points. METHODS: One hundred fifty-four patients scheduled for ambulatory shoulder arthroscopy were randomly assigned to receive a single-injection interscalene block under ultrasound guidance with either 40 mL (control) or 20 mL (intervention) and intravenous sedation. The primary outcome was the change in ipsilateral handgrip strength in the postanesthesia care unit (PACU) measured with a dynamometer. Secondary end points were recorded, including negative inspiratory force, incidences of hoarseness and Horner syndrome, time to readiness for discharge from PACU, time to discharge from PACU, patient satisfaction, time to block resolution, and pain scores. RESULTS: Postoperative handgrip strength was greater in the 20-mL group compared with the 40-mL group (difference in means, 2.3 kg [95% confidence interval, 0.6-4.0 kg]; P = 0.009). A smaller proportion of patients in the intervention group experienced hoarseness postoperatively compared with the control group (odds ratio, 0.26 [95% confidence interval, 0.08 0.82]; P = 0.015). Patient satisfaction and duration of analgesia were similar in both groups. CONCLUSIONS: When used for surgical anesthesia for shoulder arthroscopies in the ambulatory setting, a 20-mL volume in an ultrasound-guided interscalene block preserves greater handgrip strength on the ipsilateral side in the PACU compared with 40 mL without significant decrease in block success, duration of analgesia, and patient satisfaction. PMID- 27281726 TI - Epidural Versus Paravertebral Nerve Block for Postoperative Analgesia in Patients Undergoing Open Liver Resection: A Randomized Clinical Trial. AB - BACKGROUND AND OBJECTIVES: Although many studies have found no difference between thoracic epidural block and unilateral thoracic paravertebral block after thoracotomy, no previous studies have compared epidural block with bilateral thoracic paravertebral block (bTPVB) in patients undergoing open liver resection. We aimed to investigate whether there was a significant analgesic advantage of thoracic epidural over bTPVB after liver resection. METHODS: This randomized, prospective, open-label study included adult patients undergoing elective open liver resection. Patients were randomized to receive either thoracic epidural block or bTPVB, through which ropivacaine (0.2%) was infused for 3 days. The primary outcome was pain Verbal Rating Scale (VRS) score (0-10) at rest and with postoperative incentive spirometry. Secondary outcomes included VRS at rest, inspired volumes during incentive spirometry, patient-controlled analgesia hydromorphone utilization, measures of hemodynamic stability, and postoperative bowel function. RESULTS: Eighty patients completed the study and received thoracic epidural block (n = 41) or bTPVBs (n = 39). No catheter-related complications were noted. The primary outcome, pain (VRS) with incentive spirometry, was significantly lower in the epidural group (epidural vs bTPVB, mean [SD]) (4.5 [2.7] vs 5.4 [2.7] at 24 hours postoperatively, and 3.2 [2.1] vs 4.6 [2.4] at 48 hours postoperatively). Maximal inspired volumes at 24 hours postoperatively (917 [379] vs 1042 [468] mL) and cumulative utilization of patient-controlled analgesia hydromorphone during the first 48 hours postoperatively (10.7 [7.9] vs 13.6 [8.5] mg) were not significantly different between groups. Decrease in mean arterial pressure from baseline at 24 hours postoperatively was greater for the epidural group (-12.6 [15.8] vs -3.8 [16.2]; P = 0.016). CONCLUSIONS: This study suggests that there is a modest analgesic advantage of thoracic epidural over bTPVBs for patients after open liver resection. PMID- 27281728 TI - Giving Priority to Lipid Administration Can Reduce Lung Injury Caused by Epinephrine in Bupivacaine-Induced Cardiac Depression. AB - BACKGROUND AND OBJECTIVES: Epinephrine is usually administered in concert with a lipid emulsion during local anesthetic toxicity. However, the timing and role of epinephrine administration in combination with a lipid emulsion remain unclear. Specifically, the temporal association of epinephrine and lipid emulsion administration with related changes in pulmonary vascular pressures that may lead to pulmonary edema and hemorrhage needs to be determined. METHODS: This study consisted of 2 parts, experiments A and B. In experiment A, 24 adult male Sprague Dawley rats were randomly divided into 3 groups (n = 8) to receive 1 of 3 treatments. All rats were anesthetized with an intraperitoneal injection of chloral hydrate, and anesthesia was maintained by sevoflurane. Each treatment group was initially given an infusion of bupivacaine (15 mg/kg) in order to produce cardiac depression. Group 1 (A-LEN) received a 30% lipid infusion (3 mL/kg) followed by a rapid epinephrine bolus (10 MUg/kg), which was then followed by a normal saline infusion (3 mL/kg). Group 2 (A-NEL) first received a normal saline infusion (3 mL/kg) followed by a rapid epinephrine bolus, which was then followed by a 30% lipid emulsion. Group 3 (A-NEN, considered a control group) first received a normal saline infusion (3 mL/kg) followed by a rapid epinephrine bolus (10 MUg/kg), which was then followed by another normal saline infusion (3 mL/kg). Lipid and normal saline infusions were administered over 1 minute, whereas epinephrine was injected rapidly. The continuous monitoring of blood pressure, heart rate, pulmonary arterial pressure, and pulmonary venous pressure occurred for 30 minutes. After the 30-minute monitoring period, lung tissue was sampled, and bronchoalveolar lavage fluid was collected. In experiment B, the experimental model and resuscitation protocol were similar to experiment A (B-LEN and B-NEL groups). In this arm of the experiment, bupivacaine concentrations of cardiac tissue were determined after the second minute of normal saline infusion. RESULTS: The A-LEN group produced the best rate pressure product when compared with the A-NEL or A-NEN group (P = 0.045, P = 0.011, respectively). In regard to pulmonary venous pressure, the A-LEN group was lower than the A-NEL or A-NEN group (P = 0.031, P = 0.006, respectively). Animals in the A-NEL and A-NEN groups rapidly developed pulmonary edema after infusion of epinephrine. The wet-to-dry ratio of the lungs in the A-LEN group was lower than that of the lungs in the A NEL group (P = 0.024).The lung permeability index of the A-LEN group was lower than that of the A-NEL group (P = 0.011). In experiment B, concentrations of bupivacaine in cardiac tissue and plasma of the B-LEN group were lower than those of the B-NEL group (P = 0.001, P = 0.03, respectively). CONCLUSIONS: Giving priority to the administration of a lipid emulsion before the administration of epinephrine can reduce lung injury in bupivacaine-induced cardiac depression in rats. PMID- 27281729 TI - Neurologic Outcomes After Low-Volume, Ultrasound-Guided Interscalene Block and Ambulatory Shoulder Surgery. AB - BACKGROUND AND OBJECTIVES: Postoperative neurologic symptoms after interscalene block and shoulder surgery have been reported to be relatively frequent. Reports of such symptoms after ultrasound-guided block have been variable. We evaluated 300 patients for neurologic symptoms after low-volume, ultrasound-guided interscalene block and arthroscopic shoulder surgery. METHODS: Patients underwent ultrasound-guided interscalene block with 16 to 20 mL of 0.5% bupivacaine or a mix of 0.2% bupivacaine/1.2% mepivacaine solution, followed by propofol/ketamine sedation for ambulatory arthroscopic shoulder surgery. Patients were called at 10 days for evaluation of neurologic symptoms, and those with persistent symptoms were called again at 30 days, at which point neurologic evaluation was initiated. Details of patient demographics and block characteristics were collected to assess any association with persistent neurologic symptoms. RESULTS: Six of 300 patients reported symptoms at 10 days (2%), with one of these patients having persistent symptoms at 30 days (0.3%). This was significantly lower than rates of neurologic symptoms reported in preultrasound investigations with focused neurologic follow-up and similar to other studies performed in the ultrasound era. There was a modest correlation between the number of needle redirections during the block procedure and the presence of postoperative neurologic symptoms. CONCLUSIONS: Ultrasound guidance of interscalene block with 16- to 20-mL volumes of local anesthetic solution results in a lower frequency of postoperative neurologic symptoms at 10 and 30 days as compared with investigations in the preultrasound period. PMID- 27281731 TI - Dr P. Prithvi Raj: A True Founding Father. PMID- 27281730 TI - Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions. AB - High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions and which ADEs most frequently led to discontinuation. Spine surgery was chosen because of its association with moderate to severe pain and a relatively high use of ketamine infusions in this population at our hospital. PMID- 27281732 TI - Like mother, like child: Offspring marital timing desires and maternal marriage timing and stability. AB - Understanding the determinants of marital timing is critical because it has implications for marital functioning and divorce. One salient predictor of marital timing is youth's desires for marriage timing. To shine light on predictors of both desires for marital timing and the timing of marriage itself, we examine offspring marital desires and maternal marriage characteristics in the National Longitudinal Survey of Youth, 1979 (NLSY79) cohort and 1979 Child and Young Adult cohort (NLSY79-CYA; biological offspring of the women in the 1979 cohort). Analyses showed that maternal cohabitation postdivorce predicted decreased expectations to ever marry in offspring. Maternal age at marriage was positively associated with offspring desires for age at marriage, but only for those whose mothers had not divorced. Maternal marital age was significantly associated with the offspring's transition into marriage even when controlling for the offspring's desires for marriage timing, but neither maternal marriage age nor offspring desires for marital timing were associated with the timing of entrance into cohabitation, whereas maternal divorce was associated with earlier cohabitation. Our findings suggest that maternal marriage characteristics, particularly divorce, are significant predictors of millennials' desires for and experiences with romantic relationships. (PsycINFO Database Record PMID- 27281733 TI - Data management architecture, University Hospital Haiti. PMID- 27281734 TI - CFTR and pHi regulation. PMID- 27281735 TI - Reply: Epithelial alkalinity and hyperproliferation in the Cftr KO intestine. PMID- 27281738 TI - Sinonasal Undifferentiated Carcinoma Presenting With Bilateral Compressive Optic Neuropathy. PMID- 27281739 TI - Fernlike Maculopathy in a Patient With Central Retinal Vein Occlusion. PMID- 27281740 TI - Hair in the Eye. PMID- 27281743 TI - A physiological and behavioral system for hearing restoration with cochlear implants. AB - Cochlear implants are neuroprosthetic devices that provide hearing to deaf patients, although outcomes are highly variable even with prolonged training and use. The central auditory system must process cochlear implant signals, but it is unclear how neural circuits adapt-or fail to adapt-to such inputs. The knowledge of these mechanisms is required for development of next-generation neuroprosthetics that interface with existing neural circuits and enable synaptic plasticity to improve perceptual outcomes. Here, we describe a new system for cochlear implant insertion, stimulation, and behavioral training in rats. Animals were first ensured to have significant hearing loss via physiological and behavioral criteria. We developed a surgical approach for multichannel (2- or 8 channel) array insertion, comparable with implantation procedures and depth in humans. Peripheral and cortical responses to stimulation were used to program the implant objectively. Animals fitted with implants learned to use them for an auditory-dependent task that assesses frequency detection and recognition in a background of environmentally and self-generated noise and ceased responding appropriately to sounds when the implant was temporarily inactivated. This physiologically calibrated and behaviorally validated system provides a powerful opportunity to study the neural basis of neuroprosthetic device use and plasticity. PMID- 27281741 TI - Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes. AB - The rapid spread of the Zika virus (ZIKV) in the Americas and its potential association with thousands of suspected cases of microcephaly in Brazil and higher rates of Guillain-Barre syndrome meet the conditions for a Public Health Emergency of International Concern, as stated by the World Health Organization in February 2016. Two months later, the Centers for Disease Control and Prevention (CDC) announced that the current available evidence supports the existence of a causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Microcephaly can be caused by several factors, and its clinical course and prognosis are difficult to predict. Other pathogens with proven teratogenicity have been identified long before the current ZIKV epidemic. Despite the growing number of cases with maternal signs of infection and/or presence of ZIKV in tissues of affected newborns or fetuses, it is currently difficult to assess the magnitude of increase of microcephaly prevalence in Brazil, as well as the role of other factors in the development of congenital neurological conditions. Meanwhile, health agencies and medical organizations have issued cautious guidelines advising health care practitioners and expectant couples traveling to, returning from, or living in affected areas. Analogous to dengue virus (DENV) epidemics, ZIKV has the potential to become endemic in all countries infested by Aedes mosquitoes, while new mutations could impact viral replication in humans, leading to increased virulence and consequently heightened chances of viral transmission to additional naive mosquito vectors. Studies are urgently needed to answer the questions surrounding ZIKV and its role in congenital neurological conditions. PMID- 27281744 TI - Proactive modulation of long-interval intracortical inhibition during response inhibition. AB - Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABAB receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a "default" nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective "brake" is applied. PMID- 27281746 TI - Stochastic slowly adapting ionic currents may provide a decorrelation mechanism for neural oscillators by causing wander in the intrinsic period. AB - Oscillatory neurons integrate their synaptic inputs in fundamentally different ways than normally quiescent neurons. We show that the oscillation period of invertebrate endogenous pacemaker neurons wanders, producing random fluctuations in the interspike intervals (ISI) on a time scale of seconds to minutes, which decorrelates pairs of neurons in hybrid circuits constructed using the dynamic clamp. The autocorrelation of the ISI sequence remained high for many ISIs, but the autocorrelation of the DeltaISI series had on average a single nonzero value, which was negative at a lag of one interval. We reproduced these results using a simple integrate and fire (IF) model with a stochastic population of channels carrying an adaptation current with a stochastic component that was integrated with a slow time scale, suggesting that a similar population of channels underlies the observed wander in the period. Using autoregressive integrated moving average (ARIMA) models, we found that a single integrator and a single moving average with a negative coefficient could simulate both the experimental data and the IF model. Feeding white noise into an integrator with a slow time constant is sufficient to produce the autocorrelation structure of the ISI series. Moreover, the moving average clearly accounted for the autocorrelation structure of the DeltaISI series and is biophysically implemented in the IF model using slow stochastic adaptation. The observed autocorrelation structure may be a neural signature of slow stochastic adaptation, and wander generated in this manner may be a general mechanism for limiting episodes of synchronized activity in the nervous system. PMID- 27281745 TI - Organization of cortico-cortical pathways supporting memory retrieval across subregions of the left ventrolateral prefrontal cortex. AB - Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC [inferior frontal gyrus (IFG) pars orbitalis] functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (IFG pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with postretrieval control processes. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high angular-resolution diffusion spectrum imaging and functional connectivity analysis in unanesthetized humans to address whether the organization of white matter connectivity differs between subregions of VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Although several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the midfrontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of VLPFC support prior functional distinctions among these regions observed in task-based and functional connectivity fMRI studies. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general. PMID- 27281747 TI - Startle reveals decreased response preparatory activation during a stop-signal task. AB - In a stop-signal task participants are instructed to initiate a movement in response to a go signal, but to inhibit this movement if an infrequent stop signal is presented after the go. Reaction time (RT) in a stop-signal task is typically longer compared with that in a simple RT task, which may be attributed to a reduced readiness to initiate the response caused by the possibility of having to inhibit the response. The purpose of this experiment was to probe the preparatory activation level of the motor response during a stop-signal task using a startling acoustic stimulus (SAS), which has been shown to involuntarily trigger sufficiently prepared responses at a short latency. Participants completed two separate tasks: a simple RT task, followed by a stop-signal RT task. During both tasks, an SAS (120 dB) was pseudorandomly presented concurrently with the go signal. As expected, RT during the simple RT task was significantly shorter than during the stop-signal task. A significant reduction in RT was noted when an SAS was presented during the simple RT task; however, during the stop-signal task, an SAS resulted in either a significant speeding or a moderate delay in RT. Additionally, the subset of SAS trial responses with the shortest RT latencies produced during the stop-signal task were also delayed compared with the short-latency SAS trial responses observed during the simple RT task. Despite evidence that a response was prepared in advance of the go signal during a stop-signal task, it appears that the amount of preparatory activation was reduced compared with that achieved during a simple RT task. PMID- 27281748 TI - Paired associative transspinal and transcortical stimulation produces plasticity in human cortical and spinal neuronal circuits. AB - Anatomical, physiological, and functional connectivity exists between the neurons of the primary motor cortex (M1) and spinal cord. Paired associative stimulation (PAS) produces enduring changes in M1, based on the Hebbian principle of associative plasticity. The present study aimed to establish neurophysiological changes in human cortical and spinal neuronal circuits by pairing noninvasive transspinal stimulation with transcortical stimulation via transcranial magnetic stimulation (TMS). We delivered paired transspinal and transcortical stimulation for 40 min at precise interstimulus intervals, with TMS being delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Transspinal-transcortical PAS markedly decreased intracortical inhibition, increased intracortical facilitation and M1 excitability with concomitant decreases of motor threshold, and reduced the soleus Hoffmann's reflex (H-reflex) low frequency-mediated homosynaptic depression. Transcortical-transspinal PAS did not affect intracortical circuits, decreased M1 excitability, and reduced the soleus H-reflex-paired stimulation pulses' mediated postactivation depression. Both protocols affected the excitation threshold of group Ia afferents and motor axons. These findings clearly indicate that the pairing of transspinal with transcortical stimulation produces cortical and spinal excitability changes based on the timing interval and functional network interactions between the two associated inputs. This new PAS paradigm may constitute a significant neuromodulation method with physiological impact, because it can be used to alter concomitantly excitability of intracortical circuits, corticospinal neurons, and spinal inhibition in humans. PMID- 27281742 TI - Approved Antiviral Drugs over the Past 50 Years. AB - Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide. PMID- 27281749 TI - Brain heating induced by near-infrared lasers during multiphoton microscopy. AB - Two-photon imaging and optogenetic stimulation rely on high illumination powers, particularly for state-of-the-art applications that target deeper structures, achieve faster measurements, or probe larger brain areas. However, little information is available on heating and resulting damage induced by high-power illumination in the brain. In the current study we used thermocouple probes and quantum dot nanothermometers to measure temperature changes induced by two-photon microscopy in the neocortex of awake and anaesthetized mice. We characterized heating as a function of wavelength, exposure time, and distance from the center of illumination. Although total power is highest near the surface of the brain, heating was most severe hundreds of micrometers below the focal plane, due to heat dissipation through the cranial window. Continuous illumination of a 1-mm(2) area produced a peak temperature increase of ~1.8 degrees C/100 mW. Continuous illumination with powers above 250 mW induced lasting damage, detected with immunohistochemistry against Iba1, glial fibrillary acidic protein, heat shock proteins, and activated caspase-3. Higher powers were usable in experiments with limited duty ratios, suggesting an approach to mitigate damage in high-power microscopy experiments. PMID- 27281750 TI - Octopamine stabilizes conduction reliability of an unmyelinated axon during hypoxic stress. AB - Mechanisms that could mitigate the effects of hypoxia on neuronal signaling are incompletely understood. We show that axonal performance of a locust visual interneuron varied depending on oxygen availability. To induce hypoxia, tracheae supplying the thoracic nervous system were surgically lesioned and action potentials in the axon of the descending contralateral movement detector (DCMD) neuron passing through this region were monitored extracellularly. The conduction velocity and fidelity of action potentials decreased throughout a 45-min experiment in hypoxic preparations, whereas conduction reliability remained constant when the tracheae were left intact. The reduction in conduction velocity was exacerbated for action potentials firing at high instantaneous frequencies. Bath application of octopamine mitigated the loss of conduction velocity and fidelity. Action potential conduction was more vulnerable in portions of the axon passing through the mesothoracic ganglion than in the connectives between ganglia, indicating that hypoxic modulation of the extracellular environment of the neuropil has an important role to play. In intact locusts, octopamine and its antagonist, epinastine, had effects on the entry to, and recovery from, anoxic coma consistent with octopamine increasing overall neural performance during hypoxia. These effects could have functional relevance for the animal during periods of environmental or activity-induced hypoxia. PMID- 27281753 TI - Efficacy of automated computer-aided diagnosis of retinal nerve fibre layer defects in healthcare screening. AB - BACKGROUND/AIMS: To evaluate the efficacy of a new automatic computer-aided detection (CAD) system for mass screening of retinal nerve fibre layer (RNFL) defects in a large population using fundus photographs. METHODS: Among the fundus photographs of 1200 consecutive subjects who visited a healthcare centre, a total of 2270 photographs appropriate for analysis were tested. The photographs were first reviewed by two expert ophthalmologists for detection of RNFL defects (gold standard manual detection). The images were then analysed using an automatic CAD system for detecting RNFL defects in various cases of glaucomatous and non glaucomatous optic neuropathy. A free-response receiver operating characteristics curve was generated to evaluate the validity of the CAD system. The results of the automatic detection were compared with those of manual detection, and sensitivity and specificity of the CAD system were calculated. RESULTS: In manual detection of 2270 photographs, 41 RNFL defects from 36 photographs (1.6%) were detected, and no RNFL defects were found in 2234 photographs (98.4%). The sensitivity of the CAD system for detecting RNFL defects was 90.2% (37/41 RNFL defects) and the specificity was 72.5% (1620/2234 photographs with no RNFL defects) at a false-positive rate of 0.36 per image. CONCLUSIONS: The new CAD system successfully detected RNFL defects during mass screening of fundus photographs in a large population who visited a healthcare centre. The proposed algorithm can be useful for clinicians in screening RNFL defects in healthcare centres. The false-positive rate is still unsatisfactory, although improved compared with the previous study. Further studies are needed to enhance the speed and specificity of image analysis using the CAD system. PMID- 27281752 TI - Two classes of excitatory synaptic responses in rat thalamic reticular neurons. AB - The thalamic reticular nucleus (nRt), composed of GABAergic cells providing inhibition of relay neurons in the dorsal thalamus, receives excitation from the neocortex and thalamus. The two excitatory pathways promoting feedback or feedforward inhibition of thalamocortical neurons contribute to sensory processing and rhythm generation. While synaptic inhibition within the nRt has been carefully characterized, little is known regarding the biophysics of synaptic excitation. To characterize the functional properties of thalamocortical and corticothalamic connections to the nRt, we recorded minimal electrically evoked excitatory postsynaptic currents from nRt cells in vitro. A hierarchical clustering algorithm distinguished two types of events. Type 1 events had larger amplitudes and faster kinetics, largely mediated by alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA) receptors, whereas type 2 responses had more prominent N-methyl-d-aspartate (NMDA) receptor contribution. Type 1 responses showed subnormal axonal propagation and paired pulse depression, consistent with thalamocortical inputs. Furthermore, responses kinetically similar to type 1 events were evoked by glutamate-mediated activation of thalamic neurons. Type 2 responses, in contrast, likely arise from corticothalamic inputs, with larger NMDA conductance and weak Mg(2+)-dependent block, suggesting that NMDA receptors are critical for the cortical excitation of reticular neurons. The long-lasting action of NMDA receptors would promote reticular cell burst firing and produce powerful inhibitory output to relay neurons proposed to be important in triggering epilepsy. This work provides the first complete voltage-clamp analysis of the kinetics and voltage dependence of AMPA and NMDA responses of thalamocortical and corticothalamic synapses in the nRt and will be critical in optimizing biologically realistic neural network models of thalamocortical circuits relevant to sensory processing and thalamocortical oscillations. PMID- 27281755 TI - Correction: Effect of the pigment-free optical zone diameter of decorative tinted soft contact lenses on visual function. PMID- 27281754 TI - Predictors of intraocular pressure change after phacoemulsification in patients with pseudoexfoliation syndrome. AB - AIM: To evaluate anterior chamber biometric factors and intraoperative metrics associated with the intraocular pressure (IOP) reduction after phacoemulsification in non-glaucomatous pseudoexfoliative syndrome (PXS) eyes. METHOD: Thirty-three patients were enrolled in this prospective interventional study. Images were excluded if they had poor quality, poor perpendicularity or inability to locate sclera spurs. Anterior chamber depth (ACD), anterior chamber area (ACA), iris thickness, iris area, iris curvature, lens vault, angle opening distance (AOD500, AOD750) and trabecular iris space area (TISA500, TISA750) were measured in qualified images using the Zhongshan Angle Assessment Program and compared preoperatively and 3 months postoperatively. Cumulative dissipated energy (CDE), aspiration time and infusion fluid usage during cataract surgery were obtained from the phacoemulsification machine's metrics record. Postoperative IOP change was compared with these anatomical and intraoperative metric parameters. RESULTS: Mean IOP was 18.1+/-3.4 mm Hg preoperatively and decreased by 3.3 mm Hg (18%) to 14.8+/-3.6 mm Hg at 3 months postoperatively (p<0.001). All angle parameters, ACD and ACA increased significantly postoperatively (p<0.001 for all) and iris curvature decreased (p<0.001). In univariate analysis, preoperative IOP (B=-0.668, p=0.002), infusion fluid usage (B=-0.040, p=0.04) and aspiration time (B=-0.045, p=0.003) were negatively associated with IOP decrease after phacoemulsification. Changes in IOP did not demonstrate significant associations with CDE measurements or anterior segment optical coherence tomography measurements, including preoperative angle, iris or anterior segment parameters. In the final multivariate regression model, preoperative IOP (B=-0.668, p=0.002) and infusion fluid usage (B=-0.041, p=0.04) were significantly associated with IOP drop and together can predict 45.1% (p=0.002) of the variability in IOP change. CONCLUSIONS: Non-glaucomatous patients with PXS experience moderate IOP reduction following phacoemulsification, and this effect is correlated with preoperative IOP, aspiration time and infusion fluid used intraoperatively. PMID- 27281751 TI - Decisions in motion: vestibular contributions to saccadic target selection. AB - The natural world continuously presents us with many opportunities for action, and thus a process of target selection must precede action execution. While there has been considerable progress in understanding target selection in stationary environments, little is known about target selection when we are in motion. Here we investigated the effect of self-motion signals on saccadic target selection in a dynamic environment. Human subjects were sinusoidally translated (f = 0.6 Hz, 30-cm peak-to-peak displacement) along an interaural axis with a vestibular sled. During the motion two visual targets were presented asynchronously but equidistantly on either side of fixation. Subjects had to look at one of these targets as quickly as possible. With an adaptive approach, the time delay between these targets was adjusted until the subject selected both targets equally often. We determined this balanced time delay for different phases of the motion in order to distinguish the effects of body acceleration and velocity on saccadic target selection. Results show that acceleration (or position, as these are indistinguishable during sinusoidal motion), but not velocity, affects target selection for saccades. Subjects preferred to look at targets in the direction of the acceleration-the leftward target was preferred when the sled accelerated to the left, and vice versa. Saccadic reaction times mimicked this selection bias by being reliably shorter to targets in the direction of acceleration. Our results provide evidence that saccade target selection mechanisms are modulated by self motion signals, which could be derived directly from the otolith system. PMID- 27281756 TI - Sweetened Beverage Consumption and Risk of Biliary Tract and Gallbladder Cancer in a Prospective Study. AB - BACKGROUND: Sugar-sweetened beverage consumption raises blood glucose concentration and has been positively associated with weight gain and type 2 diabetes, all of which have been implicated in the development of biliary tract cancer (BTC). This study examined the hypothesis that sweetened beverage consumption is positively associated with risk of BTC in a prospective study. METHODS: The study population comprised 70 832 Swedish adults (55.9% men, age 45 83 years) from the Swedish Mammography Cohort and Cohort of Swedish Men who were free of cancer and diabetes and completed a food frequency questionnaire at baseline. Incident BTC case patients were ascertained through linkage with the Swedish Cancer Register. Cox proportional hazards regression model was used to analyze the data. All statistical tests were two-sided. RESULTS: During a mean follow-up of 13.4 years, 127 extrahepatic BTC case patients (including 71 gallbladder cancers) and 21 intrahepatic BTC case patients were ascertained. After adjustment for other risk factors, women and men in the highest category of combined sugar-sweetened and artificially sweetened beverage consumption had a statistically significantly increased risk of extrahepatic BTC and gallbladder cancer. The multivariable hazard ratios for two or more servings per day (200 mL/serving) of sweetened beverages compared with no consumption were 1.79 (95% confidence interval [CI] = 1.02 to 3.13) for extrahepatic BTC and 2.24 (95% CI = 1.02 to 4.89) for gallbladder cancer. The corresponding hazard ratio for intrahepatic BTC was 1.69 (95% CI = 0.41 to 7.03). CONCLUSIONS: These findings support the hypothesis that high consumption of sweetened beverages may increase the risk of BTC, particularly gallbladder cancer. PMID- 27281757 TI - Editorial. PMID- 27281758 TI - African-American Congregational Care and Counseling: Transcending Universal and Culturally-Specific Barriers. AB - This article addresses two major African-American congregational care needs: (1) helping suffering people to access sustained mental health care, particularly in a large/mega-church; and (2) helping suffering people with multi-layered challenges to access appropriate, skilled care that transcends traditional barriers and is consistent with their faith. One model of congregational care is presented with concrete examples of how cultural, theological, and strategic concerns are discussed, with broad implications for diverse faith communities. PMID- 27281759 TI - The Taboo of Retirement for Diocesan Catholic Priests. AB - This paper considers Catholic priests in the USA and their freedom to retire, the constraints that may restrain them from retirement, and the financial and psychological variables that impact them in ministry and in future retirement. Implications for pastoral care and counseling are considered. PMID- 27281760 TI - Pastoral Care and Counseling with Military Families. AB - The complex human experience of military service and the stress suffered by millions of military families each time a loved one deploys present unique challenges and opportunities in providing pastoral care and counseling. War and military service impact many facets of our society, as well as generational and interpersonal relationships. This article speaks to both academic and practitioner communities, and provides a vision for effective pastoral care and counseling with military families drawing on resources from family systems theory. PMID- 27281761 TI - The Interactive Play and a Persuasive God: A Psychoanalytic Approach to Re envisioning Pastoral Care and Counseling. AB - The purpose of this article is to present a sketch of a new image of pastoral care and counseling, which reflects the psychoanalytic understanding of the interacting transference and countertransference matrix, along with a process view of God in a mutually influencing relationship with creatures. A more effective approach in pastoral care and counseling can be conceptualized as the interactive play in which pastoral caregivers and receivers co-create a therapeutic relationship with their own past experiences and their creative capabilities. The interactive play is a concept of describing the mutually influencing relationship in the transference and countertransference interchange. The article introduces the concept of a persuasive God as a new image of pastoral care and counseling which includes aspects of the mutually interacting process in play. PMID- 27281762 TI - Pneumaplasticity: Rewiring the Human Soul. AB - We human beings continue to wrestle with our identities as spiritual people, both individually and collectively. This article proposes a synthesized perspective on human spirituality, introducing the concept of pneumaplasticity, which allows us to move beyond the spiritual limits common to several major faith traditions to see how our spiritual selves can adapt and rewire to facilitate meaning-making and continued discernment of our ever-developing senses of identity and meaning. This concept is of particular value to professionals providing spiritual care in any setting. PMID- 27281764 TI - In the Media. PMID- 27281763 TI - 'Is Grandma Still There?' A Pastoral and Ethical Reflection on the Soul and Continuing Self-identity in Deeply Forgetful People. AB - This metaphysical and pastoral reflection focuses on a question that over several decades has been posed to me by many family caregivers for deeply forgetful people (persons with dementia). The question may take different forms: Is my loved one still there underneath all of this confusion? Is my loved one's soul still present? Will she come to rest fully intact in the arms of a Supreme Being? Could she be 'gone' but already somewhere experiencing the fullness of divine love? This reflection provides a pastoral response to this big question that has to do with the need to find meaning in caring for deeply forgetful people. PMID- 27281765 TI - In the Media. PMID- 27281766 TI - In the Media. PMID- 27281767 TI - The Silent We. PMID- 27281768 TI - If You Want a True Friend. PMID- 27281769 TI - James L. Griffith, Religion That Heals, Religion That Harms: A Guide for Clinical Practice. PMID- 27281770 TI - Vacek, Heather H. (2015) Madness: American Protestant Responses to Mental Illness. PMID- 27281771 TI - The Journal of Pastoral Care & Counseling Quiz. PMID- 27281772 TI - Increased Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes and Retinopathy. AB - OBJECTIVE: We sought to examine the presence and severity of brain small vessel disease (SVD) in patients with type 2 diabetes and diabetic retinopathy (DR) compared with those without DR. RESEARCH DESIGN AND METHODS: We evaluated 312 patients with type 2 diabetes without previous cardiovascular disease (men 51%; mean age 57 years; age range 40-75 years); 153 patients (49%) had DR. MRI was performed to evaluate the presence and severity (age-related white matter changes scale) of white matter lesions (WMLs) and lacunes, and transcranial Doppler ultrasound was used to measure the Gosling pulsatility index (PI) of the middle cerebral artery (MCA). RESULTS: The prevalence of lesions of cerebral SVD (WML and/or lacunes) was higher in patients with DR (40.2% vs. 30.1% without DR, P = 0.04). Age (P < 0.01) and systolic blood pressure (P = 0.02) were associated with the presence of SVD. The severity of SVD was associated with age and the presence of DR (P < 0.01 and P = 0.01, respectively). Patients with DR showed a higher MCA PI compared with those without DR (P < 0.01). Age, systolic and diastolic blood pressure, and retinopathy and its severity were associated with an increased MCA PI (P < 0.01 for all variables). A positive correlation was found between MCA PI values and the presence and severity of SVD (P < 0.01 for both variables). CONCLUSIONS: Patients with type 2 diabetes who have DR have an increased burden of cerebral SVD compared with those without DR. Our findings suggest that the brain is a target organ for microangiopathy, similar to other classic target organs, like the retina. PMID- 27281774 TI - Seasonality of tweets related to multiple sclerosis. PMID- 27281773 TI - Arterial Stiffness Is Positively Associated With 18F-fluorodeoxyglucose Positron Emission Tomography-Assessed Subclinical Vascular Inflammation in People With Early Type 2 Diabetes. AB - OBJECTIVE: Type 2 diabetes is accompanied by premature atherosclerosis and arterial stiffness. The underlying association remains incompletely understood. The possible relationship between subclinical arterial inflammation assessed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and arterial stiffness was investigated in patients with early type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes (n = 44), without cardiovascular disease and any type of antidiabetic medication, were studied (median age 63 years [interquartile range 54-66], men:women 27:17). Arterial inflammation was quantified as the FDG uptake maximal standardized uptake value (SUVmax). SUVmax was corrected for the prescan glucose level. A target-to-background ratio (TBR) was calculated by dividing the SUVmax of the arteries by the SUVmean of the caval veins (blood pool). TBRs were calculated for four individual segments (carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries) and averaged for the total aortic tree (meanTBR). Arterial stiffness was assessed as central systolic blood pressure (cSBP), carotid-femoral pulse wave velocity (PWV), and augmentation index (AIx). RESULTS: The meanTBR was significantly associated with PWV (R = 0.47, P = 0.001) and cSBP (R = 0.45, P = 0.003) but not with AIx. TBR of each separate segment was also significantly associated with PWV and cSBP. In a multiple linear regression model including age, sex, BMI, hemoglobin A1c (HbA1c), hs-CRP, cholesterol, cSBP, and PWV, PWV was the strongest determinant of meanTBR. CONCLUSIONS: In patients with type 2 diabetes, FDG-PET/CT-imaged subclinical arterial inflammation is positively associated with determinants of arterial stiffness. PMID- 27281775 TI - International consensus statement on injury surveillance in cricket: a 2016 update. AB - Cricket was the first sport to publish recommended methods for injury surveillance in 2005. Since then, there have been changes to the nature of both cricket and injury surveillance. Researchers representing the major cricket playing nations met to propose changes to the previous recommendations, with an agreed voting block of 14. It was decided that 10 of 14 votes (70%) were required to add a new definition element and 11 of 14 (80%) were required to amend a previous definition. In addition to the previously agreed 'Match time-loss' injury, definitions of 'General time-loss', 'Medical presentation', 'Player reported' and 'Imaging-abnormality' injuries are now provided. Further, new injury incidence units of match injuries per 1000 player days, and annual injuries per 100 players per year are recommended. There was a shift towards recommending a greater number of possible definitions, due to differing contexts and foci of cricket research (eg, professional vs amateur; injury surveillance systems vs specific injury category studies). It is recommended that researchers use and report as many of the definitions as possible to assist both comparisons between studies within cricket and with those from other sports. PMID- 27281776 TI - Injuries in world junior ice hockey championships between 2006 and 2015. AB - BACKGROUND: Detailed injury data are not available for international ice hockey tournaments played by junior athletes. We report the incidence, type, mechanism and severity of injuries in males under ages 18 and 20 at junior ice hockey World Championships during 2006-2015. METHODS: All injuries in the International Ice Hockey Federation World Junior under-20 (WJ U20) Championship and under-18 (WJ U18) Championship were collected over a 9-year period using a strict injury definition, a standardised injury reporting system and diagnoses made by a team physician. RESULTS: 633 injuries were recorded in 1326 games over a 9-year period, resulting in an injury rate (IR) of 11.0 per 1000 player-games and 39.8/1000 player-game hours. The IRs in all tournaments were 4.3/1000 player games for the head and face, 3.2 for the upper body, 2.6 for the lower body and 1.0 for the spine and trunk. A laceration was the most common injury type followed by a sprain. Lacerations accounted for 80% (IR 3.6) of facial injuries in WJ U20 tournaments. The shoulder was the most common injury site (IR 2.0) in WJ U18 tournaments. Board contact was the mechanism for 59% of these shoulder injuries. Concussion was the most common head and face injury (46%; IR 1.2) in WJ U18 tournaments. CONCLUSIONS AND RECOMMENDATIONS: The risk of injury among male junior ice hockey players was lower than the reported rates in adult men but higher than that in women. Facial lacerations were common in U20 junior players (WJ U20) since most wear only partial facial protection (visor). The IR for shoulder injuries was high in U18 junior players (WJ U18). Suggested strategies for injury prevention include full facial protection for all players and flexible board and glass for all junior tournaments. PMID- 27281777 TI - Screening for risk factors: if you liked it then you should have put a number on it. PMID- 27281778 TI - Physical, nutritional, cognitive and combination interventions reduce frailty in community-dwelling prefrail and frail older people. PMID- 27281779 TI - Radiation risk due to CT diagnostics of acute appendicitis. PMID- 27281781 TI - Using observational research to obtain a picture of nursing practice. PMID- 27281780 TI - Spermometer: electrical characterization of single boar sperm motility. AB - OBJECTIVE: To study single sperm boar motility using electrical impedance measurements in a microfluidic system. DESIGN: Comparison of the optical data and electrical impedance data. SETTING: Research laboratory at a university. ANIMAL(S): Boar semen sample were used. INTERVENTION(S): A microfluidic system is developed that is able to spatially confine single boar sperm cells and allows noninvasive analysis of their motility on the single cell level. Using this system, the single sperm motility was affected by changing the temperature or adding chemical stimuli (caffeine). The retrieved electrical impedance and video data were processed using Matlab. MAIN OUTCOME MEASURE(S): The sperm beat frequency and amplitude determined from the electrical impedance and video data. RESULT(S): The electrically measured sperm beat frequency was verified by optical analysis and in correspondence. Furthermore the microfluidic platform allowed single sperm analysis by altering the sperm by temperature and chemical stimuli. CONCLUSION(S): This platform could be exploited as a potential tool to study sperm cells on the single cell level and to perform advanced sperm selection for intracytoplasmic sperm injection (ICSI) applications. PMID- 27281782 TI - Simultaneous Enrichment of Cysteine-containing Peptides and Phosphopeptides Using a Cysteine-specific Phosphonate Adaptable Tag (CysPAT) in Combination with titanium dioxide (TiO2) Chromatography. AB - Cysteine is a rare and conserved amino acid involved in most cellular functions. The thiol group of cysteine can be subjected to diverse oxidative modifications that regulate many physio-pathological states. In the present work, a Cysteine specific Phosphonate Adaptable Tag (CysPAT) was synthesized to selectively label cysteine-containing peptides (Cys peptides) followed by their enrichment with titanium dioxide (TiO2) and subsequent mass spectrometric analysis. The CysPAT strategy was developed using a synthetic peptide, a standard protein and subsequently the strategy was applied to protein lysates from Hela cells, achieving high specificity and enrichment efficiency. In particular, for Cys proteome analysis, the method led to the identification of 7509 unique Cys peptides from 500 MUg of HeLa cell lysate starting material. Furthermore, the method was developed to simultaneously enrich Cys peptides and phosphorylated peptides. This strategy was applied to SILAC labeled Hela cells subjected to 5 min epidermal growth factor (EGF) stimulation. In total, 10440 unique reversibly modified Cys peptides (3855 proteins) and 7339 unique phosphopeptides (2234 proteins) were simultaneously identified from 250 MUg starting material. Significant regulation was observed in both phosphorylation and reversible Cys modification of proteins involved in EGFR signaling. Our data indicates that EGF stimulation can activate the well-known phosphorylation of EGFR and downstream signaling molecules, such as mitogen-activated protein kinases (MAPK1 and MAPK3), however, it also leads to substantial modulation of reversible cysteine modifications in numerous proteins. Several protein tyrosine phosphatases (PTPs) showed a reduction of the catalytic Cys site in the conserved putative phosphatase HC(X)5R motif indicating an activation and subsequent de phosphorylation of proteins involved in the EGF signaling pathway. Overall, the CysPAT strategy is a straight forward, easy and promising method for studying redox proteomics and the simultaneous enrichment strategy offers an excellent solution for characterization of cross-talk between phosphorylation and redox induced reversible cysteine modifications. PMID- 27281783 TI - Autoimmune Regulator (AIRE) Is Expressed in Spermatogenic Cells, and It Altered the Expression of Several Nucleic-Acid-Binding and Cytoskeletal Proteins in Germ Cell 1 Spermatogonial (GC1-spg) Cells. AB - Autoimmune regulator (AIRE) is a gene associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE is expressed heavily in the thymic epithelial cells and is involved in maintaining self tolerance through regulating the expression of tissue-specific antigens. The testes are the most predominant extrathymic location where a heavy expression of AIRE is reported. Homozygous Aire-deficient male mice were infertile, possibly due to impaired spermatogenesis, deregulated germ cell apoptosis, or autoimmunity. We report that AIRE is expressed in the testes of neonatal, adolescent, and adult mice. AIRE expression was detected in glial cell derived neurotrophic factor receptor alpha (GFRalpha)(+) (spermatogonia), GFRalpha( )/synaptonemal complex protein (SCP3)(+) (meiotic), and GFRalpha( )/Phosphoglycerate kinase 2 (PGK2)(+) (postmeiotic) germ cells in mouse testes. GC1-spg, a germ-cell-derived cell line, did not express AIRE. Retinoic acid induced AIRE expression in GC1-spg cells. Ectopic expression of AIRE in GC1-spg cells using label-free LC-MS/MS identified a total of 371 proteins that were differentially expressed. 100 proteins were up-regulated, and 271 proteins were down-regulated. Data are available via ProteomeXchange with identifier PXD002511. Functional analysis of the differentially expressed proteins showed increased levels of various nucleic-acid-binding proteins and transcription factors and a decreased level of various cytoskeletal and structural proteins in the AIRE overexpressing cells as compared with the empty vector-transfected controls. The transcripts of a select set of the up-regulated proteins were also elevated. However, there was no corresponding decrease in the mRNA levels of the down regulated set of proteins. Molecular function network analysis indicated that AIRE influenced gene expression in GC1-spg cells by acting at multiple levels, including transcription, translation, RNA processing, protein transport, protein localization, and protein degradation, thus setting the foundation in understanding the functional role of AIRE in germ cell biology. PMID- 27281785 TI - On Strengthening the MCP Editorial Leadership. PMID- 27281788 TI - Correction. PMID- 27281784 TI - Identification of RNA-binding Proteins in Macrophages by Interactome Capture. AB - Pathogen components, such as lipopolysaccharides of Gram-negative bacteria that activate Toll-like receptor 4, induce mitogen activated protein kinases and NFkappaB through different downstream pathways to stimulate pro- and anti inflammatory cytokine expression. Importantly, post-transcriptional control of the expression of Toll-like receptor 4 downstream signaling molecules contributes to the tight regulation of inflammatory cytokine synthesis in macrophages. Emerging evidence highlights the role of RNA-binding proteins (RBPs) in the post transcriptional control of the innate immune response. To systematically identify macrophage RBPs and their response to LPS stimulation, we employed RNA interactome capture in LPS-induced and untreated murine RAW 264.7 macrophages. This combines RBP-crosslinking to RNA, cell lysis, oligo(dT) capture of polyadenylated RNAs and mass spectrometry analysis of associated proteins. Our data revealed 402 proteins of the macrophage RNA interactome including 91 previously not annotated as RBPs. A comparison with published RNA interactomes classified 32 RBPs uniquely identified in RAW 264.7 macrophages. Of these, 19 proteins are linked to biochemical activities not directly related to RNA. From this group, we validated the HSP90 cochaperone P23 that was demonstrated to exhibit cytosolic prostaglandin E2 synthase 3 (PTGES3) activity, and the hematopoietic cell-specific LYN substrate 1 (HCLS1 or HS1), a hematopoietic cell specific adapter molecule, as novel macrophage RBPs. Our study expands the mammalian RBP repertoire, and identifies macrophage RBPs that respond to LPS. These RBPs are prime candidates for the post-transcriptional regulation and execution of LPS-induced signaling pathways and the innate immune response. Macrophage RBP data have been deposited to ProteomeXchange with identifier PXD002890. PMID- 27281789 TI - Correction. PMID- 27281790 TI - Optimizing HIV/AIDS resources in Armenia: increasing ART investment and examining HIV programmes for seasonal migrant labourers. AB - INTRODUCTION: HIV prevalence is declining in key populations in Armenia including in people who inject drugs (PWID), men who have sex with men, prison inmates, and female sex workers (FSWs); however, prevalence is increasing among Armenians who seasonally migrate to work in countries with higher HIV prevalence, primarily to the Russian Federation. METHODS: We conducted a modelling study using the Optima model to assess the optimal resource allocation to meet targets from the 2013 to 2016 national strategic plan to minimize HIV incidence and AIDS-related deaths by 2020. Demographic, epidemiological, behavioural, and programme cost data from 2000 through 2014 were used to inform the model. The levels of coverage that could be attained among targeted populations with different investments, as well as their expected outcomes, were determined. In the absence of evidence of the efficacy of HIV programmes targeted at seasonal labour migrants, we conducted a sensitivity analysis to determine the cost-effective funding threshold for the seasonal labour migrant programme. RESULTS: The optimization analysis revealed that shifts in funding allocations could further minimize incidence and deaths by 2020 within the available resource envelope. The largest emphasis should be on antiretroviral therapy (ART), with the optimal investment to increase treatment coverage by 40%. Optimal investments also involve increases in opiate substitution therapy and FSW programmes, as well as maintenance of other prevention programmes for PWID and prevention of mother-to-child transmission. Additional funding for these increases should come from budgets for general population programmes. This is projected to avert 17% of new infections and 29% of AIDS-related deaths by 2020 compared to a baseline scenario of maintaining 2013 spending. Our sensitivity analysis demonstrated that, at current spending, coverage of annual testing among migrants of at least 43% should be achieved to warrant continuation of funding for this programme. CONCLUSIONS: Optimization of HIV/AIDS investment in Armenia, with a main priority for scaling-up ART, and less emphasis on primary prevention in the general non-key population could significantly reduce incidence and deaths by 2020. PMID- 27281791 TI - Sialorrhea in children with cerebral palsy. AB - OBJECTIVE: To review the literature on sialorrhea in children with cerebral palsy. SOURCE OF DATA: Non-systematic review using the keywords "sialorrhea" and "child" carried out in the PubMed(r), LILACS(r), and SciELO(r) databases during July 2015. A total of 458 articles were obtained, of which 158 were analyzed as they were associated with sialorrhea in children; 70 had content related to sialorrhea in cerebral palsy or the assessment and treatment of sialorrhea in other neurological disorders, which were also assessed. DATA SYNTHESIS: The prevalence of sialorrhea is between 10% and 58% in cerebral palsy and has clinical and social consequences. It is caused by oral motor dysfunction, dysphagia, and intraoral sensitivity disorder. The severity and impact of sialorrhea are assessed through objective or subjective methods. Several types of therapeutic management are described: training of sensory awareness and oral motor skills, drug therapy, botulinum toxin injection, and surgical treatment. CONCLUSIONS: The most effective treatment that addresses the cause of sialorrhea in children with cerebral palsy is training of sensory awareness and oral motor skills, performed by a speech therapist. Botulinum toxin injection and the use of anticholinergics have a transient effect and are adjuvant to speech therapy; they should be considered in cases of moderate to severe sialorrhea or respiratory complications. Atropine sulfate is inexpensive and appears to have good clinical response combined with good safety profile. The use of trihexyphenidyl for the treatment of sialorrhea can be considered in dyskinetic forms of cerebral palsy or in selected cases. PMID- 27281792 TI - Renal medullary and urinary oxygen tension during cardiopulmonary bypass in the rat. AB - Renal hypoxia could result from a mismatch in renal oxygen supply and demand, particularly in the renal medulla. Medullary hypoxic damage is believed to give rise to acute kidney injury, which is a prevalent complication of cardiac surgery performed on cardiopulmonary bypass (CPB). To determine the mechanisms that could lead to medullary hypoxia during CPB in the rat kidney, we developed a mathematical model which incorporates (i) autoregulation of renal blood flow and glomerular filtration rate, (ii) detailed oxygen transport and utilization in the renal medulla and (iii) oxygen transport along the ureter. Within the outer medulla, the lowest interstitial tissue P$_{?rm O2}$, which is an indicator of renal hypoxia, is predicted near the thick ascending limbs. Interstitial tissue P$_{?rm O2}$ exhibits a general decrease along the inner medullary axis, but urine P$_{?rm O2}$ increases significantly along the ureter. Thus, bladder urinary P$_{?rm O2}$ is predicted to be substantially higher than medullary P$_{?rm O2}$. The model is used to identify the phase of cardiac surgery performed on CPB that is associated with the highest risk for hypoxic kidney injury. Simulation results indicate that the outer medulla's vulnerability to hypoxic injury depends, in part, on the extent to which medullary blood flow is autoregulated. With imperfect medullary blood flow autoregulation, the model predicts that the rewarming phase of CPB, in which medullary blood flow is low but medullary oxygen consumption remains high, is the phase in which the kidney is most likely to suffer hypoxic injury. PMID- 27281793 TI - Thrombopoietin receptor agonists shift the balance of Fcgamma receptors toward inhibitory receptor IIb on monocytes in ITP. AB - Elevated expression of the activating Fcgamma receptor (FcgammaR) I and FcgammaRIIa together with decreased expression of the inhibitory FcgammaRIIb are involved in the pathogenesis of primary immune thrombocytopenia (ITP). Thrombopoietin receptor agonists (TPO-RAs) have been used clinically for the management of ITP; however, little is known about the effect of TPO-RAs on FcgammaR modulation in ITP. In this prospective study, we measured the alteration in monocyte FcgammaR expression from 21 corticosteroid-resistant/relapsed patients with chronic ITP receiving eltrombopag therapy. Results showed that the mRNA and protein levels of FcgammaRIIb were significantly elevated after 6-week eltrombopag treatment. Concurrently, FcgammaRI and IIa levels decreased remarkably, whereas FcgammaRIII expression did not change. In vitro phagocytosis assays indicated that a shift in the balance of FcgammaR toward inhibitory FcgammaRIIb on monocytes was accompanied with a considerable decrease in monocyte/macrophage phagocytic capacity. The response to eltrombopag therapy in patients with ITP was associated with FcgammaR phenotype and functional changes of monocytes/macrophages. Moreover, the plasma transforming growth factor-beta1 (TGF-beta1) concentrations increased significantly in eltrombopag responders. Modulation of monocyte FcgammaR balance by TPO-RAs was also found in a murine model of ITP established by transferring splenocytes from immunized CD61 knockout mice into CD61(+) severe combined immunodeficient mice. Romiplostim administration in ITP mice significantly upregulated inhibitory FcgammaRII expression and downregulated activating FcgammaRI expression. These findings showed that recovery of platelet counts after TPO-RA treatment in ITP is associated with the restoration of FcgammaR balance toward the inhibitory FcgammaRIIb on monocytes, and suggested that thrombopoietic agents have a profound effect on immune modulation in ITP. This study is registered at ClinicalTrials.gov as #NCT01864512. PMID- 27281796 TI - Compulsory treatment: ask who the patient really is. A response to Mirko Garasic. PMID- 27281797 TI - The unethical use of ethical rhetoric: the case of flibanserin and pharmacologisation of female sexual desire. AB - The current debate around sexual dysfunctions focuses mostly on the pharmacological regulation of lowered sexual desire in women. The Food and Drug Administration approval of the first drug-Addyi-to treat this condition was preceded by a campaign, in which ethically saturated arguments were used to lobby policy makers. This article provides a critical evaluation of these arguments. In particular, we focus our attention on deceitful and unethical use of moral arguments and concepts. First, we present the context in which hypoactive sexual desire disorder is defined as a serious medical condition, showing how non medical and non-scientific influences shaped the understanding of the problem. Further, we demonstrate how in current discussions regarding lower sexual interest attention has been shifted from psychosocial to pharmacological solutions and we trace the ethical consequences of such a change. We argue that, in addition to typical detrimental effects of overmedicalisation, there are new serious perils. In particular, we demonstrate that it is highly probable that pharmacologisation of female desire-contrary to the emancipatory declarations of the drug proponents-exerts pressure on women and narrows the range of potential choices they can make. As a result, it is inconsistent with the very idea of free choice. PMID- 27281794 TI - XLF deficiency results in reduced N-nucleotide addition during V(D)J recombination. AB - Repair of DNA double-strand breaks (DSBs) by the nonhomologous end-joining pathway (NHEJ) is important not only for repair of spontaneous breaks but also for breaks induced in developing lymphocytes during V(D)J (variable [V], diversity [D], and joining [J] genes) recombination of their antigen receptor loci to create a diverse repertoire. Mutations in the NHEJ factor XLF result in extreme sensitivity for ionizing radiation, microcephaly, and growth retardation comparable to mutations in LIG4 and XRCC4, which together form the NHEJ ligation complex. However, the effect on the immune system is variable (mild to severe immunodeficiency) and less prominent than that seen in deficiencies of NHEJ factors ARTEMIS and DNA-dependent protein kinase catalytic subunit, with defects in the hairpin opening step, which is crucial and unique for V(D)J recombination. Therefore, we aimed to study the role of XLF during V(D)J recombination. We obtained clinical data from 9 XLF-deficient patients and performed immune phenotyping and antigen receptor repertoire analysis of immunoglobulin (Ig) and T cell receptor (TR) rearrangements, using next-generation sequencing in 6 patients. The results were compared with XRCC4 and LIG4 deficiency. Both Ig and TR rearrangements showed a significant decrease in the number of nontemplated (N) nucleotides inserted by terminal deoxynucleotidyl transferase, which resulted in a decrease of 2 to 3 amino acids in the CDR3. Such a reduction in the number of N nucleotides has a great effect on the junctional diversity, and thereby on the total diversity of the Ig and TR repertoire. This shows that XLF has an important role during V(D)J recombination in creating diversity of the repertoire by stimulating N-nucleotide insertion. PMID- 27281795 TI - Deep phenotyping of Tregs identifies an immune signature for idiopathic aplastic anemia and predicts response to treatment. AB - Idiopathic aplastic anemia (AA) is an immune-mediated and serious form of bone marrow failure. Akin to other autoimmune diseases, we have previously shown that in AA regulatory T cells (Tregs) are reduced in number and function. The aim of this study was to further characterize Treg subpopulations in AA and investigate the potential correlation between specific Treg subsets and response to immunosuppressive therapy (IST) as well as their in vitro expandability for potential clinical use. Using mass cytometry and an unbiased multidimensional analytical approach, we identified 2 specific human Treg subpopulations (Treg A and Treg B) with distinct phenotypes, gene expression, expandability, and function. Treg B predominates in IST responder patients, has a memory/activated phenotype (with higher expression of CD95, CCR4, and CD45RO within FOXP3(hi), CD127(lo) Tregs), expresses the interleukin-2 (IL-2)/STAT5 pathway and cell-cycle commitment genes. Furthermore, in vitro-expanded Tregs become functional and take on the characteristics of Treg B. Collectively, this study identifies human Treg subpopulations that can be used as predictive biomarkers for response to IST in AA and potentially other autoimmune diseases. We also show that Tregs from AA patients are IL-2-sensitive and expandable in vitro, suggesting novel therapeutic approaches such as low-dose IL-2 therapy and/or expanded autologous Tregs and meriting further exploration. PMID- 27281798 TI - Predictive genetic testing for neurodegenerative conditions: how should conflicting interests within families be managed? AB - Predictive genetic testing for a neurodegenerative condition in one individual in a family may have implications for other family members, in that it can reveal their genetic status. Herein a complex clinical case is explored where the testing wish of one family member was in direct conflict to that of another. The son of a person at 50% risk of an autosomal dominant neurodegenerative condition requested testing to reveal his genetic status. The main reason for the request was if he had the familial mutation, he and his partner planned to utilise preimplantation genetic diagnosis to prevent his offspring having the condition. His at-risk parent was clear that if they found out they had the mutation, they would commit suicide. We assess the potential benefits and harms from acceding to or denying such a request and present an approach to balancing competing rights of individuals within families at risk of late-onset genetic conditions, where family members have irreconcilable differences with respect to predictive testing. We argue that while it may not be possible to completely avoid harm in these situations, it is important to consider the magnitude of risks, and make every effort to limit the potential for adverse outcomes. PMID- 27281799 TI - A Slow- Compared with a Fast-Release Form of Oral Arginine Increases Its Utilization for Nitric Oxide Synthesis in Overweight Adults with Cardiometabolic Risk Factors in a Randomized Controlled Study. AB - BACKGROUND: Oral l-arginine supplements can have a beneficial effect on nitric oxide (NO)-related functions when subjects have cardiovascular disease risk factors. OBJECTIVE: The study was designed to determine the utilization for NO synthesis of oral l-arginine as a function of the cardiometabolic risk and the speed of absorption by comparing immediate-release arginine (IR-Arg), as in supplements, and sustained-release arginine (SR-Arg), which mimics the slow release of dietary arginine. METHODS: In a randomized, single-blind, 2-period crossover, controlled trial (1 wk of treatment, >2 wk of washout), using [(15)N (15)N-(guanidino)]-arginine for the first morning dose, we compared the bioavailability (secondary outcome) and utilization for NO synthesis (primary outcome) of 1.5 g IR- and SR-Arg 3 times/d in 12 healthy overweight [body mass index (BMI; in kg/m(2)): 25-30] adults with the hypertriglyceridemic waist phenotype [HTW; plasma triglycerides (TGs): >150 mg/dL; waist circumference: >94 cm (men) or >80 cm (women)] and 15 healthy control adults (CON; BMI: 18.5-25; no elevated TGs and waist circumference). RESULTS: Plasma oral arginine areas under the curve were lower after supplementation with SR-Arg than with IR-Arg (112 +/- 52.3 and 142 +/- 50.8 MUmol ? h/L; P < 0.01). The utilization of oral arginine for NO synthesis was 58% higher in HTW subjects than in CON subjects and higher with SR-Arg than with IR-Arg (P < 0.05 both), particularly in HTW subjects (group by-treatment interaction, P < 0.05). In HTW subjects administered the SR form, utilization for NO synthesis was 32% higher than with the IR form and 87% higher than in CON subjects who were administered the SR form. CONCLUSION: In overweight adults with the HTW phenotype, a slow- compared with a fast-release form of oral arginine markedly favors the utilization of arginine for NO synthesis. The utilization of low-dose, slow-release arginine for NO synthesis is higher in overweight adults with the HTW phenotype than in healthy controls, suggesting that the sensitivity of NO synthesis to the dietary arginine supply increases with cardiometabolic risk. The trial was registered at clinicaltrials.gov as NCT02352740. PMID- 27281800 TI - l-Arginine Supplementation Alleviates Postprandial Endothelial Dysfunction When Baseline Fasting Plasma Arginine Concentration Is Low: A Randomized Controlled Trial in Healthy Overweight Adults with Cardiometabolic Risk Factors. AB - BACKGROUND: Vascular endothelial dysfunction, the hallmark of early atherosclerosis, is induced transiently by a high-fat meal. High doses of free l arginine supplements reduce fasting endothelial dysfunction. OBJECTIVE: We sought to determine the effects of a low dose of a sustained-release (SR) l-arginine supplement on postprandial endothelial function in healthy overweight adults with cardiometabolic risk factors and to investigate whether this effect may vary by baseline arginine status. METHODS: In a randomized, double-blind, 2-period crossover, placebo-controlled trial (4-wk treatment, 4-wk washout), we compared the effects of 1.5 g SR-l-arginine 3 times/d (4.5 g/d) with placebo in 33 healthy overweight adults [body mass index (BMI, in kg/m(2)): 25 to >30] with the hypertriglyceridemic waist (HTW) phenotype [plasma triglycerides > 150 mg/dL; waist circumference > 94 cm (men) or > 80 cm (women)]. The main outcome variable tested was postprandial endothelial function after a high-fat meal (900 kcal), as evaluated by use of flow-mediated dilation (FMD) and Framingham reactive hyperemia index (fRHI), after each treatment. By use of subgroup analysis, we determined whether the effect was related to the baseline plasma arginine concentration. RESULTS: In the total population, the effects of SR-arginine supplementation on postprandial endothelial function were mixed and largely varied with baseline fasting arginine concentration (P-interaction < 0.05). In the lower half of the population (below the median of 78.2 MUmol arginine/L plasma), but not the upper half, SR-arginine supplementation attenuated the postprandial decrease in both FMD (29% decrease with SR-arginine compared with 50% decrease with placebo) and fRHI (5% increase with SR-arginine compared with 49% decrease with placebo), resulting in significantly higher mean +/- SEM values with SR-arginine (FMD: 4.0% +/- 0.40%; fRHI: 0.41 +/- 0.069) than placebo (FMD: 2.9% +/- 0.31%; fRHI: 0.21 +/- 0.060) at the end of the postprandial period (P < 0.05). CONCLUSIONS: Supplementation with low-dose SR-arginine alleviates postprandial endothelial dysfunction in healthy HTW adults when the baseline plasma arginine concentration is relatively low. The benefits of arginine supplementation may be linked to a lower ability to mobilize endogenous arginine for nitric oxide synthesis during a postprandial challenge. This trial was registered at clinicaltrials.gov as NCT02354794. PMID- 27281801 TI - Whole Blood omega-3 Fatty Acids Are Inversely Associated with Carotid Intima Media Thickness in Indigenous Mexican Women. AB - BACKGROUND: Long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may reduce the risk of atherosclerosis. The association between n-3 PUFAs and cardiovascular disease may vary across different populations, and there is limited information on Hispanic individuals with mixed Amerindian and European origin. OBJECTIVE: We evaluated the cross-sectional relations between whole blood n-3 PUFAs and carotid intima-media thickness (IMT) in Mexican women living in Mexico and assessed whether this relation was different in women who spoke an indigenous language compared with women who did not. METHODS: In 2012-2013, we assessed the association between blood n-3 PUFAs and IMT in 1306 women free of disease in Chiapas and Yucatan, Mexico. We categorized blood n-3 PUFAs (% of total FAs) in quartiles and adjusted linear regression models by age, indigenous language, site, socioeconomic status, education, smoking, menopause, diabetes, hypertension, hypercholesterolemia, body mass index, physical activity, and diet. We stratified analyses by indigenous/nonindigenous language speakers (n = 315 of 991). RESULTS: Whole blood n-3 PUFAs (means +/- SDs) were 3.58% +/- 0.78% of total FAs. We did not observe a significant association between n-3 PUFAs and IMT in the overall study population. However, the adjusted mean difference of IMT was -6.5% (95% CI: -10.7%, -2.3%; P-trend < 0.0001) for indigenous women in the highest quartile compared with the lowest quartile of blood n-3 PUFAs. In nonindigenous women, we did not observe an association (-0.6%; 95% CI: -3.0%, 1.8%, comparing extreme quartiles; P-trend = 1.00). CONCLUSIONS: Overall, circulating n-3 PUFAs were not associated with IMT. However, we observed a strong statistically significant inverse association with IMT in indigenous Mexican women. Future studies should evaluate genetic markers that may reflect differences in n-3 PUFA metabolism across populations. PMID- 27281802 TI - A Daily Snack Containing Leafy Green Vegetables, Fruit, and Milk before and during Pregnancy Prevents Gestational Diabetes in a Randomized, Controlled Trial in Mumbai, India. AB - BACKGROUND: Prospective observational studies suggest that maternal diets rich in leafy green vegetables and fruit may help prevent gestational diabetes mellitus (GDM). OBJECTIVE: Our objective was to test whether increasing women's dietary intake of leafy green vegetables, fruit, and milk before conception and throughout pregnancy reduced their risk of GDM. METHODS: Project SARAS ("excellent") (2006-2012) was a nonblinded, individually randomized, controlled trial in women living in slums in the city of Mumbai, India. The interventions included a daily snack made from leafy green vegetables, fruit, and milk for the treatment group or low-micronutrient vegetables (e.g., potato and onion) for the control group, in addition to the usual diet. Results for the primary outcome, birth weight, have been reported. Women were invited to take an oral-glucose tolerance test (OGTT) at 28-32 wk gestation to screen for GDM (WHO 1999 criteria). The prevalence of GDM was compared between the intervention and control groups, and Kernel density analysis was used to compare distributions of 120-min plasma glucose concentrations between groups. RESULTS: Of 6513 women randomly assigned, 2291 became pregnant; of these, 2028 reached a gestation of 28 wk, 1008 (50%) attended for an OGTT, and 100 (9.9%) had GDM. In an intention-to treat analysis, the prevalence of GDM was reduced in the treatment group (7.3% compared with 12.4% in controls; OR: 0.56; 95% CI: 0.36, 0.86; P = 0.008). The reduction in GDM remained significant after adjusting for prepregnancy adiposity and fat or weight gain during pregnancy. Kernel density analysis showed that this was explained by the fact that fewer women in the treatment group had a 2-h glucose concentration in the range 7.5-10.0 mmol/L. CONCLUSIONS: In low-income settings, in which women have a low intake of micronutrient-rich foods, improving dietary micronutrient quality by increasing intake of leafy green vegetables, fruit, and/or milk may have an important protective effect against the development of GDM. This trial was registered at www.controlled-trials.com as ISRCTN62811278. PMID- 27281803 TI - A Model-Based Approach to Identify Classes and Respective Cutoffs of the Brazilian Household Food Insecurity Measurement Scale. AB - BACKGROUND: The Brazilian Household Food Insecurity Measurement Scale (EBIA) is the main tool for assessing household food insecurity (FI) in Brazil, assisting in monitoring and improving national public policies to promote food security. Based on the sum of item scores, households have been classified into 4 levels of FI, with the use of cutoffs arising from expert discussions informed by psychometric analyses and policy considerations. OBJECTIVES: This study aimed to identify homogeneous latent groups corresponding to levels of FI, examine whether such subgroups could be defined from discriminant cutoffs applied to the overall EBIA raw score, and compare these cutoffs against those currently used. METHODS: A cross-sectional population-based study with a representative sample of 1105 households from a low-income metropolitan area of Rio de Janeiro was conducted. Latent class factor analysis (LCFA) models were applied to the answers to EBIA's items to identify homogeneous groups, obtaining the number of latent classes for FI measured by the scale. Based on this and a thorough classification agreement evaluation, optimal cutoffs for discriminating between different severity levels of FI were ascertained. Model-based grouping and the official EBIA classification cutoffs were also contrasted. RESULTS: LCFA identified 4 homogeneous groups with a very high degree of class separation (entropy = 0.906), endorsing the classification of EBIA as a 4-level measure of FI. Two sets of cutoffs were identified to separate such groups according to household type: 1/2, 5/6, and 10/11 in households with children and adolescents (score range: 0-14); and 1/2, 3/4, and 5/6 in adult-only households (score range: 0-7). CONCLUSION: Although roughly classifying EBIA as in previous studies, the current approach suggests that, in terms of raw score, households endorsing only one item of the scale would be better classified by being placed in the same stratum as those remaining negative on all items. PMID- 27281804 TI - Postnatal Iron Deficiency Alters Brain Development in Piglets. AB - BACKGROUND: Cognitive deficits associated with postnatal iron deficiency (ID) suggest abnormal brain development, but little is known about animals with gyrencephalic brains. OBJECTIVE: The objective was to assess the impact of ID on brain development in piglets. METHODS: Male and female Yorkshire piglets were reared from postnatal day (PD) 2 until PD 29 or 30 by using milk replacer adequate [control (CON)] or deficient (100 compared with 10 mg/kg) in iron and subjected to MRI to assess brain macrostructure, microstructure, and metabolites in the dorsal hippocampi and intervening space. After MRI, brains were collected for histology. Hematocrit, hemoglobin, and liver iron were measured to determine iron status. RESULTS: Hematocrit and hemoglobin in ID piglets were less than CON after PD 14 (P < 0.001), and at the study end liver iron in ID piglets was less than CON (P < 0.001). Brain region volumes were not affected by ID, but changes in brain composition were evident. ID piglets had less white matter in 78,305 voxels, with large clusters in the hippocampus and cortex. ID piglets had less gray matter in 13,625 voxels primarily in cortical areas and more gray matter in 28,017 voxels, most notably in olfactory bulbs and hippocampus. The major effect of ID on white matter was supported by lower fractional anisotropy values in the corpus callosum (0.300 compared with 0.284, P = 0.006) and in whole brain white matter (0.313 compared with 0.307, P = 0.002) in ID piglets. In coronal brain sections, corpus callosum width was less (P = 0.043) in ID piglets. Inositol was lower (P = 0.01) and phosphocholine was higher (P = 0.03) in hippocampus of ID piglets. CONCLUSIONS: Postnatal ID in piglets affects brain development, especially white matter. If the effects of ID persist, it might explain the lasting detrimental effects on cognition. PMID- 27281805 TI - Coffee Consumption Is Positively Associated with Longer Leukocyte Telomere Length in the Nurses' Health Study. AB - BACKGROUND: Coffee is an important source of antioxidants, and consumption of this beverage is associated with many health conditions and a lower mortality risk. However, no study, to our knowledge, has examined whether varying coffee or caffeine consumption levels are associated with telomere length, a biomarker of aging whose shortening can be accelerated by oxidative stress. OBJECTIVE: We performed a large comprehensive study on how coffee consumption is associated with telomere length. METHODS: We used data from the Nurses' Health Study (NHS), a prospective cohort study of female nurses that began in 1976. We examined the cross-sectional association between coffee consumption and telomere length in 4780 women from the NHS. Coffee consumption information was obtained from validated food-frequency questionnaires, and relative telomere length was measured in peripheral blood leukocytes by the quantitative real-time polymerase chain reaction. Unconditional logistic regression was used to obtain ORs when the telomere length outcome was dichotomized at the median. Linear regression was used for tests of trend with coffee consumption and telomere length as continuous variables. RESULTS: Higher total coffee consumption was significantly associated with longer telomeres after potential confounding adjustment. Compared with non coffee drinkers, multivariable ORs for those drinking 2 to <3 and >=3 cups of coffee/d were, respectively, 1.29 (95% CI: 0.99, 1.68) and 1.36 (95% CI: 1.04, 1.78) (P-trend = 0.02). We found a significant linear association between caffeine consumption from all dietary sources and telomere length (P-trend = 0.02) after adjusting for potential confounders, but not after additionally adjusting for total coffee consumption (P-trend = 0.37). CONCLUSIONS: We found that higher coffee consumption is associated with longer telomeres among female nurses. Future studies are needed to better understand the influence of coffee consumption on telomeres, which may uncover new knowledge of how coffee consumption affects health and longevity. PMID- 27281806 TI - Neither Preconceptional Weekly Multiple Micronutrient nor Iron-Folic Acid Supplements Affect Birth Size and Gestational Age Compared with a Folic Acid Supplement Alone in Rural Vietnamese Women: A Randomized Controlled Trial. AB - BACKGROUND: Maternal nutritional status before and during early pregnancy plays a critical role in fetal growth and development. The benefits of periconception folic acid (FA) supplementation in the prevention of neural tube defects is well recognized, but the evidence for preconception micronutrient interventions for improving pregnancy outcomes is limited. OBJECTIVE: This study aimed to evaluate whether preconception supplementation with weekly iron and folic acid (IFA) or multiple micronutrients (MMs) improves birth outcomes compared with FA alone. METHODS: We recruited 5011 women of reproductive age in a double-blind, randomized controlled trial in Vietnam and provided weekly supplements containing either 2800 MUg FA, 60 mg Fe and 2800 MUg FA (IFA), or the same amount of FA and iron plus other MMs until they conceived (n = 1813). All pregnant women received daily IFA through delivery, and were followed up for birth outcomes, including birth weight, gestational age, preterm delivery and small for gestational age (SGA). Group comparisons were done with the use of ANOVA or chi-square tests for both intention-to-treat (n = 1599) and per-protocol analyses (women consumed supplements >=26 wk before conception; n = 824). Effect modification by baseline underweight or anemia status was tested with the use of generalized linear models. RESULTS: The mean age of the women was 26 y, 30% were underweight, and <10% were nulliparous. The groups were similar for most baseline characteristics. The mean +/- SD duration of the preconception intervention was 33 +/- 25 wk and compliance was high (>90%). Infants born to the 3 groups of women did not differ (P >= 0.05) on mean +/- SD birth weight (3076.8 +/- 444.5 g) or gestational age (39.2 +/- 2.0 wk), or prevalence of SGA (12%), low birth weight (5%) and preterm delivery (10%). There were no significant differences in women who consumed supplements >=26 wk before conception or by baseline underweight or anemia. CONCLUSION: Weekly supplementation with MMs or IFA before conception did not affect birth outcomes compared with FA in rural Vietnamese women. The trial was registered at clinicaltrials.gov as NCT01665378. PMID- 27281807 TI - Adolescent Snacking Behaviors Are Associated with Dietary Intake and Weight Status. AB - BACKGROUND: Most adolescents consume >=1 snack/d; exploring the relevance of snacking patterns for overall diet and weight status is important to guide dietary counseling and public health strategies for obesity prevention. OBJECTIVE: This study examined intake of common energy-dense snack foods, total number of snacks consumed, frequency of consuming snacks prepared away from home, and frequency of snacking while watching television in adolescents and how these behaviors may be linked to diet and weight status. Relations were examined with attention to potential confounders that may help explain the mixed findings of previous research. METHODS: Survey measures of snacking behavior, a food frequency questionnaire, and anthropometric measurements were completed by 2793 adolescents (53.2% girls, mean age = 14.4 y) in Minneapolis-St. Paul school classrooms in 2009-2010. Linear regression was used to examine associations with adjustment for sociodemographic characteristics and other potential confounding factors, such as meal skipping, underreporting energy intake, dieting to lose weight, and physical activity. RESULTS: Adolescents reported consuming a mean of 2.2 energy-dense snack food servings/d and 4.3 snacks/d and purchasing snacks prepared away from home on 3.2 occasions/wk. More than two-thirds of adolescents reported that they sometimes, usually, or always consumed a snack while watching television. The measures of snacking were directly associated (P < 0.01) with higher energy, lower fruit/vegetable, higher sugar-sweetened beverage, and more frequent fast-food intakes in all models except for one: energy-dense snack food servings were not related to sugar-sweetened beverage intake. A direct relation between daily servings of energy-dense snack foods and body mass index (BMI) z score was found; however, the snacking behaviors were inversely related to BMI z score (P < 0.01). CONCLUSIONS: The observed cross-sectional associations suggest that snack consumption is a risk factor for poor diet, but unless energy-dense foods are consumed, snacking does not consistently contribute to overweight in US adolescents. PMID- 27281808 TI - A Summary of Pathways or Mechanisms Linking Preconception Maternal Nutrition with Birth Outcomes. AB - Population, human, animal, tissue, and molecular studies show collectively and consistently that maternal nutrition in the pre- or periconception period influences fetal growth and development, which subsequently affects the individual's long-term health. It is known that nutrition during pregnancy is an important determinant of the offspring's growth and health. However, now there is evidence that the mother's nutritional status at conception also influences pregnancy outcome and long-term health. For example, the mother's nutritional status at conception influences the way energy is partitioned between maternal and fetal needs. Furthermore, placental development during the first weeks of gestation reflects maternal nutrition and establishes mechanisms for balancing maternal and fetal nutritional needs. Also, maternal nutritional signals at fertilization influence epigenetic remodeling of fetal genes. These findings all indicate that maternal parenting begins before conception. The following papers from a symposium on preconception nutrition presented at the 2015 Scientific Sessions and Annual Meeting of the ASN emphasize the importance of maternal nutrition at conception on the growth and long-term health of the child. PMID- 27281809 TI - Development of Intrinsically Labeled Eggs and Poultry Meat for Use in Human Metabolic Research. AB - BACKGROUND: Stable isotope amino acids are regularly used as tracers to examine whole-body and muscle protein metabolism in humans. To accurately assess in vivo dietary protein digestion and absorption kinetics, the amino acid tracer is required to be incorporated within the dietary protein food source (i.e., intrinsically labeled protein). OBJECTIVE: We assessed the practicality of producing eggs and poultry meat intrinsically labeled with l-[5,5,5-(2)H3]leucine through noninvasive oral tracer administration. METHODS: A specifically formulated diet containing 0.52% leucine was supplemented with 0.3% l-[5,5,5 (2)H3]leucine and subsequently fed to 3 laying hens (Lohmann LSL Whites) for 55 d. On day 55, the hens were slaughtered and their meat, bones, and organs were harvested to determine tissue labeling. In Expt. 1, 2 healthy young men [mean +/- SEM age: 22 +/- 1.5 y; mean +/- SEM body mass index (BMI; in kg/m(2)): 23.7 +/- 0.5] ingested 18 g l-[5,5,5-(2)H3]leucine-labeled egg protein. In Expt. 2, 2 healthy young men (mean +/- SEM age: 20.0 +/- 0.0 y; mean +/- SEM BMI: 26.4 +/- 3.1) ingested 28 g l-[5,5,5-(2)H3]leucine-labeled poultry meat protein. Plasma samples (Expts. 1 and 2) and muscle biopsies (Expt. 1) were collected before and after labeled-food ingestion. RESULTS: High tracer labeling [>20 mole percent excess (MPE)] in the eggs was obtained after 7 d and maintained throughout the feeding protocol (P < 0.05). Over a 55-d period, ~850 g egg protein (145 eggs) was produced, with a mean +/- SEM tracer enrichment of 22.0 +/- 0.8 MPE. Mean +/- SEM l-[5,5,5-(2)H3]leucine enrichment in the meat was 9.6 +/- 0.1 MPE. In Expts. 1 and 2, the consumption of labeled eggs and poultry meat protein increased plasma l-[5,5,5-(2)H3]leucine enrichment, with mean +/- SEM peak values of 6.7 +/ 0.1 MPE and 4.0 +/- 0.9 MPE, respectively. The mean +/- SEM 5-h postprandial increase in myofibrillar l-[5,5,5-(2)H3]leucine enrichment after egg ingestion in healthy young men was 0.051 +/- 0.008 MPE (Expt. 1). CONCLUSION: We demonstrated the feasibility of producing intrinsically labeled eggs and poultry meat for use in human metabolic research. PMID- 27281811 TI - Physical Activity Performed in the Evening Increases the Overnight Muscle Protein Synthetic Response to Presleep Protein Ingestion in Older Men. AB - BACKGROUND: The age-related decline in skeletal muscle mass is partly attributed to anabolic resistance to food intake. Dietary protein ingestion before sleep could be used as a nutritional strategy to compensate for anabolic resistance. OBJECTIVE: The present study assessed whether physical activity performed in the evening can augment the overnight muscle protein synthetic response to presleep protein ingestion in older men. METHODS: In a parallel group design, 23 healthy older men (mean +/- SEM age: 71 +/- 1 y) were randomly assigned to ingest 40 g protein intrinsically labeled with l-[1-(13)C]-phenylalanine and l-[1-(13)C] leucine before going to sleep with (PRO+EX) or without (PRO) performing physical activity earlier in the evening. Overnight protein digestion and absorption kinetics and myofibrillar protein synthesis rates were assessed by combining primed, continuous infusions of l-[ring-(2)H5]-phenylalanine, l-[1-(13)C] leucine, and l-[ring-(2)H2]-tyrosine with the ingestion of intrinsically labeled casein protein. Muscle and blood samples were collected throughout overnight sleep. RESULTS: Protein ingested before sleep was normally digested and absorbed, with 54% +/- 2% of the protein-derived amino acids appearing in the circulation throughout overnight sleep. Overnight myofibrillar protein synthesis rates were 31% (0.058% +/- 0.002%/h compared with 0.044% +/- 0.003%/h; P < 0.01; based on l [ring-(2)H5]-phenylalanine) and 27% (0.074% +/- 0.004%/h compared with 0.058% +/- 0.003%/h; P < 0.01; based on l-[1-(13)C]-leucine) higher in the PRO+EX than in the PRO treatment. More dietary protein-derived amino acids were incorporated into de novo myofibrillar protein during overnight sleep in PRO+EX than in PRO treatment (0.042 +/- 0.002 compared with 0.033 +/- 0.002 mole percent excess; P < 0.05). CONCLUSIONS: Physical activity performed in the evening augments the overnight muscle protein synthetic response to presleep protein ingestion and allows more of the ingested protein-derived amino acids to be used for de novo muscle protein synthesis during overnight sleep in older men. This trial was registered at Nederlands Trial Register as NTR3885. PMID- 27281810 TI - 13C Natural Abundance of Serum Retinol Is a Novel Biomarker for Evaluating Provitamin A Carotenoid-Biofortified Maize Consumption in Male Mongolian Gerbils. AB - BACKGROUND: Crops such as maize, sorghum, and millet are being biofortified with provitamin A carotenoids to ensure adequate vitamin A (VA) intakes. VA assessment can be challenging because serum retinol concentrations are homeostatically controlled and more sensitive techniques are resource-intensive. OBJECTIVES: We investigated changes in serum retinol relative differences of isotope amount ratios of (13)C/(12)C (delta(13)C) caused by natural (13)C fractionation in C3 compared with C4 plants as a biomarker to detect provitamin A efficacy from biofortified (orange) maize and high-carotene carrots. METHODS: The design was a 2 * 2 * 2 maize (orange compared with white) by carrot (orange compared with white) by a VA fortificant (VA+ compared with VA-) in weanling male Mongolian gerbils (n = 55), which included a 14-d VA depletion period and a 62-d treatment period (1 baseline and 8 treatment groups; n = 5-7/group). Liver VA and serum retinol were quantified, purified by HPLC, and analyzed by GC combustion isotope ratio mass spectrometry for (13)C. RESULTS: Treatments affected liver VA concentrations (0.048 +/- 0.039 to 0.79 +/- 0.24 MUmol/g; P < 0.0001) but not overall serum retinol concentrations (1.38 +/- 0.22 MUmol/L). Serum retinol and liver VA delta(13)C were significantly correlated (R(2) = 0.92; P < 0.0001). Serum retinol delta(13)C differentiated control groups that consumed white maize and white carrots (-27.1 +/- 1.2 delta(13)C0/00) from treated groups that consumed orange maize and white carrots (-21.6 +/- 1.4 delta(13)C0/00 P < 0.0001) and white maize and orange carrots (-30.6 +/- 0.7 delta(13)C0/00 P < 0.0001). A prediction model demonstrated the relative contribution of orange maize to total dietary VA for groups that consumed VA from mixed sources. CONCLUSIONS: Provitamin A efficacy and quantitative estimation of the relative contribution to dietary VA were demonstrated with the use of serum retinol delta(13)C. This method could be used for maize efficacy or effectiveness studies and with other C4 crops biofortified with provitamin A carotenoids (e.g., millet, sorghum). Advantages include no extrinsic tracer dose, 1 blood sample, and higher sensitivity than serum retinol concentrations alone. PMID- 27281812 TI - Preconceptional Nutrition Interventions for Adolescent Girls and Adult Women: Global Guidelines and Gaps in Evidence and Policy with Emphasis on Micronutrients. AB - Much of the global nutrition efforts in recent years have been focused on improving the nutritional status of children during the window of the first 1000 d of life, from conception to 2 y of age. However, as the world transitions from the Millennium Development Goals to the Sustainable Development Goals, women's and adolescent girls' overall health and well-being are being placed at the center of the global agenda. It is also increasingly recognized that a woman's nutritional status before pregnancy affects maternal and child outcomes and thus needs to be improved to ensure optimal outcomes. This article reviews the global picture of preconception nutrition in women and girls, including some of the key factors that influence women's outcomes, as well as their children's outcomes, if they do become pregnant. This article describes the current global guidelines on preconceptional nutrition interventions for girls and women; highlights related gaps in evidence, guidelines, and policy; and discusses research to forward the agenda of improving women's and girls' preconceptional nutrition. PMID- 27281813 TI - Soluble Corn Fiber Increases Calcium Absorption Associated with Shifts in the Gut Microbiome: A Randomized Dose-Response Trial in Free-Living Pubertal Females. AB - BACKGROUND: Soluble corn fiber (SCF; 12 g fiber/d) is shown to increase calcium absorption efficiency, associated with shifts in the gut microbiota in adolescent males and females who participated in a controlled feeding study. OBJECTIVE: We evaluated the dose response of 0, 10, and 20 g fiber/d delivered by PROMITOR SCF 85 (85% fiber) on calcium absorption, biochemical bone properties, and the fecal microbiome in free-living adolescents. METHODS: Healthy adolescent females (n = 28; aged 11-14 y) randomly assigned into a 3-phase, double-blind, crossover study consumed SCF for 4 wk at each dose (0, 10, and 20 g fiber/d from SCF) alongside their habitual diet and were followed by 3-d clinical visits and 3-wk washout periods. Stable isotope ((44)Ca and (43)Ca) enrichment in pooled urine was measured by inductively coupled plasma mass spectrometry. Fecal microbial community composition was assessed by high-throughput sequencing (Illumina) of polymerase chain reaction-amplified 16S rRNA genes. Mixed model ANOVA and Friedman analysis were used to determine effects of SCF on calcium absorption and to compare mean microbial proportions, respectively. RESULTS: Calcium absorption increased significantly with 10 (13.3% +/- 5.3%; P = 0.042) and 20 g fiber/d (12.9% +/- 3.6%; P = 0.026) from SCF relative to control. Significant differences in fecal microbial community diversity were found after consuming SCF (operational taxonomic unit measures of 601.4 +/- 83.5, 634.5 +/- 83.8, and 649.6 +/- 75.5 for 0, 10, and 20 g fiber/d, respectively; P < 0.05). Proportions of the genus Parabacteroides significantly increased with SCF dose (1.1% +/- 0.8%, 2.1% +/- 1.6%, and 3.0% +/- 2.0% for 0, 10, and 20 g fiber/d from SCF, respectively; P < 0.05). Increases in calcium absorption positively correlated with increases in Clostridium (r = 0.44, P = 0.023) and unclassified Clostridiaceae (r = 0.40, P = 0.040). CONCLUSIONS: SCF, a nondigestible carbohydrate, increased calcium absorption in free-living adolescent females. Two groups of bacteria may be involved, one directly fermenting SCF and the second fermenting SCF metabolites further, thereby promoting increased calcium absorption. This trial was registered at clinicaltrials.gov as NCT01660503. PMID- 27281814 TI - Performance assessment of two lysis methods for direct identification of yeasts from clinical blood cultures using MALDI-TOF mass spectrometry. AB - In cases of fungal infection of the bloodstream, rapid species identification is crucial to provide adapted therapy and thereby ameliorate patient outcome. Currently, the commercial Sepsityper kit and the sodium-dodecyl sulfate (SDS) method coupled with MALDI-TOF mass spectrometry are the most commonly reported lysis protocols for direct identification of fungi from positive blood culture vials. However, the performance of these two protocols has never been compared on clinical samples. Accordingly, we performed a two-step survey on two distinct panels of clinical positive blood culture vials to identify the most efficient protocol, establish an appropriate log score (LS) cut-off, and validate the best method. We first compared the performance of the Sepsityper and the SDS protocols on 71 clinical samples. For 69 monomicrobial samples, mass spectrometry LS values were significantly higher with the SDS protocol than with the Sepsityper method (P < .0001), especially when the best score of four deposited spots was considered. Next, we established the LS cut-off for accurate identification at 1.7, based on specimen DNA sequence data. Using this LS cut-off, 66 (95.6%) and 46 (66.6%) isolates were correctly identified at the species level with the SDS and the Sepsityper protocols, respectively. In the second arm of the survey, we validated the SDS protocol on an additional panel of 94 clinical samples. Ninety two (98.9%) of 93 monomicrobial samples were correctly identified at the species level (median LS = 2.061). Overall, our data suggest that the SDS method yields more accurate species identification of yeasts, than the Sepsityper protocol. PMID- 27281815 TI - Dyspnoea in a patient with unilateral lung agenesis. PMID- 27281816 TI - Cardiac arrest leadership: in need of resuscitation? AB - BACKGROUND: Leadership skills directly correlate with the quality of technical performance of cardiopulmonary resuscitation (CPR) and clinical outcomes. Despite an improved focus on non-technical skills in CPR training, the leadership of cardiac arrests is often variable. AIMS: To assess the perceptions of leadership and team working among members of a cardiac arrest team and to evaluate future training needs. METHODS: Cross-sectional survey of 102 members of a cardiac arrest team at an Acute Hospital Trust in the UK with 892 inpatient beds. Responses sought from doctors, nurses and healthcare assistants to 12 rated statements and 4 dichotomous questions. RESULTS: Of 102 responses, 81 (79%) were from doctors and 21 (21%) from nurses. Among specialist registrars 90% agreed or strongly agreed that there was clear leadership at all arrests compared with between 28% and 49% of nurses and junior doctors respectively. Routine omission of key leadership tasks was reported by as many as 80% of junior doctors and 50% of nurses. Almost half of respondents reported non-adherence with Advanced Life Support (ALS) guidelines. Among junior members of the team, 36% felt confident to lead an arrest and 75% would welcome further dedicated cardiac arrest leadership training. CONCLUSIONS: Leadership training is integrated into the ALS (Resus Council, UK) qualification. However, this paper found that in spite of this training; standards of leadership are variable. The findings suggest a pressing need for further dedicated cardiac arrest leadership training with a focus on improving key leadership tasks such as role assignment, team briefing and debriefing. PMID- 27281817 TI - Use of medical abbreviations and acronyms: knowledge among medical students and postgraduates. AB - INTRODUCTION: Inappropriate use of abbreviations and acronyms in healthcare has become an international patient safety issue. The aim of this study was to assess the knowledge of medical abbreviations and acronyms among residents of the department of medicine at a tertiary-care hospital. METHODS: Internal medicine residents (IMRs), subspecialty residents (SRs) and students were asked to complete a self-administered questionnaire which comprised standard abbreviations used in medicine and its various subspecialties. Scores obtained by the residents were classified into three categories: >70% correct answers; 50-69% correct answers; <50% correct answers. RESULTS: A total of 77 IMRs, SRs and medical students participated. Overall, good responses were achieved by 53 (68.8%), 16 (20.8%) attained satisfactory responses, and eight (10.4%) had unsatisfactory scores. The majority of SRs achieved good responses (19/22 (86%)), followed by IMRs (30/40 (75%)) and students (4/15 (26.7%)). Evaluation of their knowledge taken from the list of 'do not use' abbreviations showed that 89.6% reported using 'Q.D.' instead of 'once a day', and 93% used 'IU' instead of the entire phrase 'international unit'. The top five 'not to use' abbreviations were ZnSO4, ug, MgSO4, IU and SC, with the frequency 100%, 96%, 94.8%, 93% and 90%, respectively. CONCLUSIONS: This study showed that there is a knowledge gap among trainees in medicine regarding the meaning and usage of common medical abbreviations. We therefore recommend proper education of trainees in medicine to ensure they understand the meaning of abbreviations and are aware of the list of 'do not use' abbreviations. PMID- 27281818 TI - Supranuclear gaze palsy and hummingbird sign. PMID- 27281819 TI - How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin. AB - Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAG interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3-7. Small angle x-ray scattering indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT.heparin complexes form beta-sheet-rich heparin-covered fibrils. Solid-state NMR reveals that heparin does not alter the sCT fibrillary core around Lys(11) but makes changes to Val(8) on the exterior side of the beta strand, possibly through contacts to Lys(18) Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting with both monomeric and aggregated sCT. PMID- 27281820 TI - Insulin Mimetic Peptide Disrupts the Primary Binding Site of the Insulin Receptor. AB - Sets of synthetic peptides that interact with the insulin receptor ectodomain have been discovered by phage display and reported in the literature. These peptides were grouped into three classes termed Site 1, Site 2, and Site 3 based on their mutual competition of binding to the receptor. Further refinement has yielded, in particular, a 36-residue Site 2-Site 1 fusion peptide, S519, that binds the insulin receptor with subnanomolar affinity and exhibits agonist activity in both lipogenesis and glucose uptake assays. Here, we report three dimensional crystallographic detail of the interaction of the C-terminal, 16 residue Site 1 component (S519C16) of S519 with the first leucine-rich repeat domain (L1) of the insulin receptor. Our structure shows that S519C16 binds to the same site on the L1 surface as that occupied by a critical component of the primary binding site, namely the helical C-terminal segment of the insulin receptor alpha-chain (termed alphaCT). In particular, the two phenylalanine residues within the FYXWF motif of S519C16 are seen to engage the insulin receptor L1 domain surface in a fashion almost identical to the respective alphaCT residues Phe(701) and Phe(705) The structure provides a platform for the further development of peptidic and/or small molecule agents directed toward the insulin receptor and/or the type 1 insulin-like growth factor receptor. PMID- 27281821 TI - RNA Exosome Complex Regulates Stability of the Hepatitis B Virus X-mRNA Transcript in a Non-stop-mediated (NSD) RNA Quality Control Mechanism. AB - Hepatitis B virus (HBV) is a stealth virus, minimally inducing the interferon system required for efficient induction of both innate and adaptive immune responses. However, 90% of acutely infected adults can clear the virus, suggesting the presence of other, interferon-independent pathways leading to viral clearance. Given the known ability of helicases to bind viral nucleic acids, we performed a functional screening assay to identify helicases that regulate HBV replication. We identified the superkiller viralicidic activity 2 like (SKIV2L) RNA helicase (a homolog of the Saccharomyces cerevisiae Ski2 protein) on the basis of its direct and preferential interaction with HBV X-mRNA. This interaction was essential for HBV X-mRNA degradation at the RNA exosome. The degradation of HBV X-mRNA at the RNA exosome was also mediated by HBS1L (HBS1 like translational GTPase) protein, a known component of the host RNA quality control system. We found that the redundant HBV-precore translation initiation site present at the 3'-end of HBV X-mRNA (3' precore) is translationally active. The initiation of translation from this site without a proper stop codon was identified by the non-stop-mediated RNA decay mechanism leading to its degradation. Although 3' precore is present in the five main HBV-RNA transcripts, only X-mRNA lacks the presence of an upstream start codons for large, middle, and small (L, M, and S) HBV surface proteins. These upstream codons are in-frame with 3' precore translation initiation site, blocking its translation from the other HBV-mRNA transcripts. To our knowledge, this is the first demonstration of the anti-viral function of the non-stop-mediated RNA decay mechanism. PMID- 27281822 TI - Effect of Hypoxia-regulated Polo-like Kinase 3 (Plk3) on Human Limbal Stem Cell Differentiation. AB - Hypoxic conditions in the cornea affect epithelial function by activating Polo like kinase 3 (Plk3) signaling and the c-Jun.AP-1 transcription complex, resulting in apoptosis of corneal epithelial cells. Hypoxic stress in the culture conditions also regulates limbal stem cell growth and fate. In this study, we demonstrate that there is a differential response of Plk3 in hypoxic stress induced primary human limbal stem (HLS) and corneal epithelial (HCE) cells, resulting in different pathways of cell fate. We found that hypoxic stress induced HLS cell differentiation by down-regulating Plk3 activity at the transcription level, which was opposite to the effect of hypoxic stress on Plk3 activation to elicit HCE cell apoptosis, detected by DNA fragmentation and TUNEL assays. Hypoxic stress-induced increases in c-Jun phosphorylation/activation were not observed in HLS cells because Plk3 expression and activity were suppressed in hypoxia-induced HLS cells. Instead, hypoxic stress-induced HLS cell differentiation was monitored by cell cycle analysis and measured by the decrease and increase in p63 and keratin 12 expression, respectively. Hypoxic stress induced Plk3 signaling to regulate c-Jun activity, resulting in limbal stem cell differentiation and center epithelial apoptosis, was also found in the corneas of wild-type and Plk3(-/-)-deficient mice. Our results, for the first time, reveal the differential effects of hypoxic stress on Plk3 activity in HLS and HCE cells. Instead of apoptosis, hypoxic stress suppresses Plk3 activity to protect limbal stem cells from death and to allow the process of HLS cell differentiation. PMID- 27281825 TI - The Babinski sign. PMID- 27281823 TI - Sprouty2 Protein Regulates Hypoxia-inducible Factor-alpha (HIFalpha) Protein Levels and Transcription of HIFalpha-responsive Genes. AB - The alpha-subunits of hypoxia-inducible factors (HIF1alpha and HIF2alpha) promote transcription of genes that regulate glycolysis and cell survival and growth. Sprouty2 (Spry2) is a modulator of receptor tyrosine kinase signaling and inhibits cell proliferation by a number of different mechanisms. Because of the seemingly opposite actions of HIFalpha subunits and Spry2 on cellular processes, we investigated whether Spry2 regulates the levels of HIF1alpha and HIF2alpha proteins. In cell lines from different types of tumors in which the decreased protein levels of Spry2 have been associated with poor prognosis, silencing of Spry2 elevated HIF1alpha protein levels. Increases in HIF1alpha and HIF2alpha protein levels due to silencing of Spry2 also up-regulated HIFalpha target genes. Using HIF1alpha as a prototype, we show that Spry2 decreases HIF1alpha stability and enhances the ubiquitylation of HIF1alpha by a von Hippel-Lindau protein (pVHL)-dependent mechanism. Spry2 also exists in a complex with HIF1alpha. Because Spry2 can also associate with pVHL, using a mutant form of Spry2 (3P/3A Spry2) that binds HIF1alpha, but not pVHL, we show that WT-Spry2, but not the 3P/3A-Spry2 decreases HIF1alpha protein levels. In accordance, expression of WT Spry2, but not 3P/3A-Spry2 results in a decrease in HIF1alpha-sensitive glucose uptake. Together our data suggest that Spry2 acts as a scaffold to bring more pVHL/associated E3 ligase in proximity of HIF1alpha and increase its ubiquitylation and degradation. This represents a novel action for Spry2 in modulating biological processes regulated by HIFalpha subunits. PMID- 27281826 TI - Ectopic crypt foci in conventional and serrated colorectal polyps. AB - AIMS: Despite almost pathognomonic status of ectopic crypt foci (ECF) in the diagnosis of traditional serrated adenoma (TSA), there are few systematic studies on their prevalence in other types of colon polyps or in adenomas adjacent to colorectal cancer (CRC). METHODS: We calculated ECF in all the polyps (n=922) removed in the colonoscopy in Oulu University Hospital in 2001. Moreover, to study ECF in precursor lesions next to CRCs, we re-examined a previously described cohort of 148 CRCs. RESULTS: ECF were seen in 53 (5.7%) polyps representing 28 (6.5%) tubular adenomas (TAs), 14 (53.8%) tubulovillous adenomas (TVAs), 2 (100.0%) villous adenomas (VAs) and 9 (100.0%) TSAs. In all TSAs and VAs, the density of ECF was higher than in TVAs and TAs. An adjacent precursor lesion was recognised in 28 of 148 (18.9%) CRCs. Twenty-four (85.7%) of these contained ECF. CONCLUSIONS: ECF can most frequently be observed in TSAs but also in many TVAs, VAs and TAs, reflecting a histological overlap between serrated and conventional polyps. Especially, precursor lesions adjacent to CRC frequently contain ECF. PMID- 27281827 TI - Effects of Head-Mounted Display on the Oculomotor System and Refractive Error in Normal Adolescents. AB - PURPOSE: To investigate the clinical effects of head-mounted display on the refractive error and oculomotor system in normal adolescents. METHODS: Sixty volunteers (age: 13 to 18 years) watched a three-dimensional movie and virtual reality application of head-mounted display for 30 minutes. The refractive error (diopters [D]), angle of deviation (prism diopters [PD]) at distance (6 m) and near (33 cm), near point of accommodation, and stereoacuity were measured before, immediately after, and 10 minutes after watching the head-mounted display. The refractive error was presented as spherical equivalent (SE). Refractive error was measured repeatedly after every 10 minutes when a myopic shift greater than 0.15 D was observed after watching the head-mounted display. RESULTS: The mean age of the participants was 14.7 +/- 1.3 years and the mean SE before watching head mounted display was -3.1 +/- 2.6 D. One participant in the virtual reality application group was excluded due to motion sickness and nausea. After 30 minutes of watching the head-mounted display, the SE, near point of accommodation, and stereoacuity in both eyes did not change significantly (all P > .05). Immediately after watching the head-mounted display, esophoric shift was observed (0.6 +/- 1.5 to 0.2 +/- 1.5 PD), although it was not significant (P = .06). Transient myopic shifts of 17.2% to 30% were observed immediately after watching the head-mounted display in both groups, but recovered fully within 40 minutes after watching the head-mounted display. CONCLUSIONS: There were no significant clinical effects of watching head-mounted display for 30 minutes on the normal adolescent eye. Transient changes in refractive error and binocular alignment were noted, but were not significant. [J Pediatr Ophthalmol Strabismus. 2016;53(4):238-245.]. PMID- 27281824 TI - Mechanism of Histone H3K4me3 Recognition by the Plant Homeodomain of Inhibitor of Growth 3. AB - Aberrant access to genetic information disrupts cellular homeostasis and can lead to cancer development. One molecular mechanism that regulates access to genetic information includes recognition of histone modifications, which is carried out by protein modules that interact with chromatin and serve as landing pads for enzymatic activities that regulate gene expression. The ING3 tumor suppressor protein contains a plant homeodomain (PHD) that reads the epigenetic code via recognition of histone H3 tri-methylated at lysine 4 (H3K4me3), and this domain is lost or mutated in various human cancers. However, the molecular mechanisms targeting ING3 to histones and the role of this interaction in the cell remain elusive. Thus, we employed biochemical and structural biology approaches to investigate the interaction of the ING3 PHD finger (ING3PHD) with the active transcription mark H3K4me3. Our results demonstrate that association of the ING3PHD with H3K4me3 is in the sub-micromolar range (KD ranging between 0.63 and 0.93 MUm) and is about 200-fold stronger than with the unmodified histone H3. NMR and computational studies revealed an aromatic cage composed of Tyr-362, Ser-369, and Trp-385 that accommodate the tri-methylated side chain of H3K4. Mutational analysis confirmed the critical importance of Tyr-362 and Trp-385 in mediating the ING3PHD-H3K4me3 interaction. Finally, the biological relevance of ING3PHD H3K4me3 binding was demonstrated by the failure of ING3PHD mutant proteins to enhance ING3-mediated DNA damage-dependent cell death. Together, our results reveal the molecular mechanism of H3K4me3 selection by the ING3PHD and suggest that this interaction is important for mediating ING3 tumor suppressive activities. PMID- 27281828 TI - Safety and Long-term Outcomes of Congenital Ptosis Surgery: A Population-Based Study. AB - PURPOSE: To report the long-term outcomes of childhood ptosis surgery in a population-based setting over a 46-year period. METHODS: In this population-based cohort study, the medical records of all patients who were residents of Olmsted County, Minnesota, diagnosed as having blepharoptosis and having undergone surgical management prior to 19 years of age (between January 1, 1965, and December 31, 2010), were retrospectively reviewed. Age at time of surgery, type of surgery, duration of follow-up, number and nature of revisions, degree of amblyopia, and postoperative lagophthalmos and dry eye were documented. RESULTS: Forty-seven children meeting inclusion criteria underwent ptosis surgery. The median age at time of first surgery was 5.6 years (range: 1.5 to 17.7 years). Fifteen of 47 (31.9%) patients required a second procedure. Three of 47 (6.4%) patients underwent three procedures. The median time was 1.1 years (range: 0.03 to 7.8 years) between the first and second surgery and 6.0 years (range: 0.3 to 6.1 years) between the second and third procedure. Seven of 47 (14.9%) patients had amblyopia. Nineteen of 47 (40.4%) patients were noted to have lagophthalmos and 3 of 47 (6.4%) presented for symptomatic dry eye postoperatively. CONCLUSIONS: In this population-based setting, more than half of the children with ptosis required only a single surgical procedure, although a significant proportion required two procedures. Postoperative lagophthalmos is common, but symptomatic dry eye is rare. [J Pediatr Ophthalmol Strabismus. 2016;53(4):212 217.]. PMID- 27281829 TI - Sutureless Lamellar Corneoscleral Patch Graft With Fibrin Sealant for Limbal Dermoid Removal. AB - A 2-year-old boy with Goldenhar syndrome had a limbal dermoid removed and covered with a lamellar corneoscleral patch graft that was attached with fibrin glue and no sutures. The graft healed and attached well. A sutureless technique is beneficial due to decreased scarring and chance of infection. PMID- 27281830 TI - Electroretinography and Pupillography in Unilateral Foveal Hypoplasia. AB - The authors describe a 3-year-old boy with unilateral foveal hypoplasia and an absence of other ocular or systemic findings. Electroretinography obtained predominantly affecting cones. Laterality of pupil constriction to red but not to blue light was observed. The colored-light pupil response can be used to predict the retinal state. PMID- 27281832 TI - Screening for Ovarian Cancer-More Hype Than Hope? PMID- 27281833 TI - Lucky: Reflecting on Relationships in Family Medicine. PMID- 27281834 TI - When to Discontinue Antiepileptic Drug Therapy for Patients in Remission. PMID- 27281835 TI - Topical Antihistamines and Mast Cell Stabilizers for Treating Allergic Conjunctivitis. PMID- 27281836 TI - Diet and Physical Activity for Cardiovascular Disease Prevention. AB - Cardiovascular disease (CVD) is the leading cause of death in the United States. One-third of these deaths may be preventable through healthy lifestyle choices including diet and physical activity. The Mediterranean diet is associated with reduced cardiovascular mortality, whereas the Dietary Approaches to Stop Hypertension (DASH) eating plan is associated with a reduced risk of coronary artery disease. Substituting dietary saturated fat with polyunsaturated fatty acids is associated with improved cardiovascular outcomes, although exogenous supplementation with omega-3 fatty acids does not improve cardiovascular outcomes. There is an association between increased sodium intake and cardiovascular risk, but reducing dietary sodium has not consistently shown a reduction in cardiovascular risk. Physical activity recommendations for adults are at least 150 minutes of moderate-intensity aerobic activity per week, 75 minutes of vigorous-intensity aerobic activity per week, or an equivalent combination. Increases in physical activity by any level are associated with reduced cardiovascular risk. Introducing muscle-strengthening activities at least twice per week in previously inactive adults is associated with improved cardiovascular outcomes. Inactive adults without known CVD can gradually increase activity to a moderate-intensity level without consulting a physician. The U.S. Preventive Services Task Force recommends behavioral counseling to promote healthy diet and physical activity in adults at high risk of CVD. Evidence of benefit for counseling patients at average risk is less established. PMID- 27281837 TI - Genital Herpes: A Review. AB - Genital herpes is a common sexually transmitted disease, affecting more than 400 million persons worldwide. It is caused by herpes simplex virus (HSV) and characterized by lifelong infection and periodic reactivation. A visible outbreak consists of single or clustered vesicles on the genitalia, perineum, buttocks, upper thighs, or perianal areas that ulcerate before resolving. Symptoms of primary infection may include malaise, fever, or localized adenopathy. Subsequent outbreaks, caused by reactivation of latent virus, are usually milder. Asymptomatic shedding of transmissible virus is common. Although HSV-1 and HSV-2 are indistinguishable visually, they exhibit differences in behavior that may affect management. Patients with HSV-2 have a higher risk of acquiring human immunodeficiency virus (HIV) infection. Polymerase chain reaction assay is the preferred method of confirming HSV infection in patients with active lesions. Treatment of primary and subsequent outbreaks with nucleoside analogues is well tolerated and reduces duration, severity, and frequency of recurrences. In patients with HSV who are HIV-negative, treatment reduces transmission of HSV to uninfected partners. During pregnancy, antiviral prophylaxis with acyclovir is recommended from 36 weeks of gestation until delivery in women with a history of genital herpes. Elective cesarean delivery should be performed in laboring patients with active lesions to reduce the risk of neonatal herpes. PMID- 27281838 TI - Diagnosis and Management of Ovarian Cancer. AB - Ovarian cancer is the most lethal gynecologic cancer. Less than one-half of patients survive for more than five years after diagnosis. Ovarian cancer affects women of all ages but is most commonly diagnosed after menopause. More than 75% of affected women are diagnosed at an advanced stage because early-stage disease is usually asymptomatic and symptoms of late-stage disease are nonspecific. The strongest risk factors are advancing age and family history of ovarian and breast cancer. Women who have symptoms concerning for ovarian cancer should undergo a physical examination, transvaginal ultrasonography, and measurement of biomarkers such as cancer antigen 125. If results are suspicious for ovarian cancer, the patient should be referred to a gynecologic oncologist. Despite the low rate of early diagnosis, guidelines recommend against routine screening for ovarian cancer in average-risk women because screening, including routine pelvic examinations, is ineffective and associated with harm. However, a recent trial found a potential benefit of annual screening using an algorithm based on serial cancer antigen 125 measurements followed by transvaginal ultrasonography for women at increased risk, as determined by the algorithm. Women with an increased risk family history should be referred for genetic counseling and, if genetic mutations (e.g., BRCA mutations) are identified, bilateral salpingo-oophorectomy can be considered for risk reduction. In both average- and high-risk women, long term hormonal contraceptive use reduces risk by about 50%. The treatment of ovarian cancer usually involves surgery, with or without intraperitoneal and intravenous chemotherapy. Primary care physicians have important roles in posttreatment surveillance and end-of-life care. PMID- 27281839 TI - Hyperkeratotic Plaques on Hands. PMID- 27281840 TI - Levonorgestrel-Releasing Intrauterine System vs. Oral Progestins for Treatment of Endometrial Hyperplasia. PMID- 27281841 TI - ACCP Releases Guideline for the Treatment of Unexplained Chronic Cough. PMID- 27281842 TI - Corticosteroids for Community-Acquired Pneumonia. PMID- 27281843 TI - Genital Herpes: What You Should Know. PMID- 27281844 TI - Ovarian Cancer. PMID- 27281845 TI - Elucidation and identification of amino acid containing membrane lipids using liquid chromatography/high-resolution mass spectrometry. AB - RATIONALE: Intact polar lipids (IPLs) are the building blocks of cell membranes, and amino acid containing IPLs have been observed to be involved in response to changing environmental conditions in various species of bacteria. High performance liquid chromatography/mass spectrometry (HPLC/MS) has become the primary method for analysis of IPLs. Many glycerol-free amino acid containing membrane lipids (AA-IPLs), which are structurally different than abundant aminophospholipids, have not been characterized using HPLC/MS. This results in many lipids remaining unrecognized in IPL analysis of microbial cultures and environmental samples, hampering the study of their occurrence and functionality. METHODS: We analyzed the amino acid containing IPLs of a number of bacteria (i.e. Gluconobacter cerinus, Cyclobacterium marinus, Rhodobacter sphaeroides, and Pedobacter heparinus) in order to decipher fragmentation pathways, and explore potential novel lipid structures using HPLC/electrospray ionization ion trap MS (HPLC/ESI-IT-MS) and HPLC/high-resolution MS (HPLC/HRMS). RESULTS: We report differentiation between glutamine and lysine lipids with the same nominal masses, novel MS fragmentation pathways of cytolipin, the lipopeptides cerilipin and flavolipin, head group hydroxylated ornithine lipids, and the novel identification of cerilipin with a hydroxylated fatty acid. CONCLUSIONS: Non glycerol AA lipids can be readily recognized as their fragmentation follows a clear pattern with initial dehydration or other loss from the head group, followed by fatty acid losses resulting in a diagnostic fragment ion. Higher level MSn and HRMS are valuable tools in characterizing AA lipid head group structural components. PMID- 27281846 TI - Author reply. PMID- 27281847 TI - [Dnmt2 is the Most Evolutionary Conserved and Enigmatic Cytosine DNA Methyltransferase in Eukaryotes]. AB - Dnmt2 is the most strongly conserved cytosine DNA methyltransferase in eukaryotes. It has been found in all organisms possessing methyltransferases of the Dnmt1 and Dnmt3 families, whereas in many others Dnmt2 is the sole cytosine DNA methyltransferase. The Dnmt2 molecule contains all conserved motifs of cytosine DNA methyltransferases. It forms 3D complexes with DNA very similar to those of bacterial DNA methyltransferases and performs cytosine methylation by a catalytic mechanism common to all cytosine DNA methyltransferases. Catalytic activity of the purified Dnmt2 with DNA substrates is very low and could hardly be detected in direct biochemical assays. Dnmt2 is the sole cytosine DNA methyltransferase in Drosophila and other dipteran insects. Its overexpression as a transgene leads to DNA hypermethylation in all sequence contexts and to an extended life span. On the contrary, a null-mutation of the Dnmt2 gene leads to a diminished life span, though no evident anomalies in development are observed. Dnmt2 is also the sole cytosine DNA methyltransferase in several protists. Similar to Drosophila these protists have a very low level of DNA methylation. Some limited genome compartments, such as transposable sequences, are probably the methylation targets in these organisms. Dnmt2 does not participate in genome methylation in mammals, but seems to be an RNA methyltransferase modifying the 38th cytosine residue in anticodon loop of certain tRNAs. This modification enhances stability of tRNAs, especially in stressful conditions. Dnmt2 is the only enzyme known to perform RNA methylation by a catalytic mechanism characteristic of DNA methyltransferases. The Dnmt2 activity has been shown in mice to be necessary for paramutation establishment, though the precise mechanisms of its participation in this form of epigenetic heredity are unknown. It seems likely, that either of the two Dnmt2 activities could become a predominant one during the evolution of different species. The high level of the Dnmt2 evolutionary conservation proves its activity to have a significant adaptive value in natural environment. PMID- 27281848 TI - [The Mechanisms of Transgenerational Inheritance and Their Potential Contribution to Human Phenotypes]. AB - As of today, classical genetics has already completed the majority of groundwork to describe the laws of inheritance, identify the causes of many human diseases, and dissect the mechanisms of transfer of genetic information from parents to offspring. However, recent studies indicate that inheritance of phenotypic traits may also occur through nongenetic factors, in particular, through epigenetic factors, that manifest their effects in a transgenerational fashion. This review discusses findings in the area of transgenerational inheritance that open a new era in modern genetics. We discuss the mechanisms of transgenerational inheritance, including DNA methylation, histone modifications, and noncoding RNA transfer, and give an overview of the approaches to detect transgenerational effects in humans. PMID- 27281849 TI - [Deinococcus radiodurans RecX and Escherichia coli RecX Proteins Are Able to Replace Each Other in vivo and in vitro]. AB - A plasmid carrying the Deinococcus radiodurans recXgene under the control of a lactose promoter decreases the Escherichia coli cell resistance to UV irradiation and gamma irradiation and also influences the conjugational recombination process. The D. radiodurans. RecX protein functions in the Escherichia coli cells similarly to the E. coli RecX protein. Isolated and purified D. radiodurans RecX and E. coli RecX proteins are able to replace each other interacting with the E. coli RecA and D. radiodurans RecA proteins in vitro. Data obtained demonstrated that regulatory interaction of RecA and RecX proteins preserves a high degree of conservatism despite all the differences in the recombination reparation system between E. coli and D. radiodurans. PMID- 27281850 TI - [Dot1 and Set2 Histone Methylases Control the Spontaneous and UV-Induced Mutagenesis Levels in the Saccharomyces cerevisiae Yeasts]. AB - In the Saccharomyces cerevisiae yeasts, the DOT1 gene product provides methylation of lysine 79 (K79) of hi- stone H3 and the SET2 gene product provides the methylation of lysine 36 (K36) of the same histone. We determined that the dot1 and set2 mutants suppress the UV-induced mutagenesis to an equally high degree. The dot1 mutation demonstrated statistically higher sensitivity to the low doses of MMC than the wild type strain. The analysis of the interaction between the dot1 and rad52 mutations revealed a considerable level of spontaneous cell death in the double dot1 rad52 mutant. We observed strong suppression of the gamma-in- duced mutagenesis in the set2 mutant. We determined that the dot1 and set2 mutations decrease the sponta- neous mutagenesis rate in both single and d ouble mutants. The epistatic interaction between the dot1 and set2 mutations and almost similar sensitivity of the corresponding mutants to the different types of DNA damage allow one to conclude that both genes are involved in the control of the same DNA repair pathways, the ho- mologous-recombination-based and the postreplicative DNA repair. PMID- 27281851 TI - [Variability of Allozyme and cpSSR Markers in the Populations of Siberian Spruce]. AB - The variability of 21 allozyme and three microsatellite loci of chloroplast DNA (cpDNA) was studied in the populations of Siberian spruce (Picea obovata Ledeb.) from Irkutsk oblast, Magadan oblast, Buryatia, and Mongolia. It was demonstrated that the highest level of genetic diversity among the examined populations at both allozyme and microsatellite loci was observed in the Tulyushka population from Irkutsk oblast. The lowest level of genetic diversity was observed in marginal isolated populations of Bogd Uul and Magadan. In the relict spruce population from Olkhon Island, differing from the other populations in the lowest allelic diversity of both types of markers, no expected decline of expected heterozygosity and haplotype diversity was observed. In this population, the variability parameters mentioned were close to the population mean. The obtained intrapopulation and intraspecific variability parameters of allozyme and microsatellite loci of chloroplast DNA and the data on the population differentiation at these loci indicate that the given markers can be used for the analysis of the population structure of Siberian spruce. PMID- 27281852 TI - [New Approach to the Mitotype Classification in Black Honeybee Apis mellifera mellifera and Iberian Honeybee Apis mellifera iberiensis]. AB - The black honeybee Apis mellifera mellifera L. is today the only subspecies of honeybee which is suitable for commercial breeding in the climatic conditions of Northern Europe with long cold winters. The main problem of the black honeybee in Russia and European countries is the preservation of the indigenous gene pool purity, which is lost as a result of hybridization with subspecies, A. m. caucasica, A. m. carnica, A. m. carpatica, and A. m. armeniaca, introduced from southern regions. Genetic identification of the subspecies will reduce the extent of hybridization and provide the gene pool conservation of the black honeybee. Modern classification of the honeybee mitotypes is mainly based on the combined use ofthe DraI restriction endonuclease recognition site polymorphism and sequence polymorphism of the mtDNA COI-COII region. We performed a comparative analysis of the mtDNA COI-COII region sequence polymorphism in the honeybees ofthe evolutionary lineage M from Ural and West European populations of black honeybee A. m. mellifera and Spanish bee A. m. iberiensis. A new approach to the classification of the honeybee M mitotypes was suggested. Using this approach and on the basis of the seven most informative SNPs of the mtDNA COI-COII region, eight honeybee mitotype groups were identified. In addition, it is suggested that this approach will simplify the previously proposed complicated mitotype classification and will make it possible to assess the level of the mitotype diversity and to identify the mitotypes that are the most valuable for the honeybee breeding and rearing. PMID- 27281853 TI - [Unidirectional Hybridization of Kaluga Acipenser dauricus Georgi, 1775 and Amur Sturgeon Acipenser schrenckii Brandt, 1869, Inferred from the Mitochondrial DNA Genotyping of Their Natural Hybrids]. AB - In 2009 through 2011, among 730 individuals of kaluga and Amur sturgeon collected in the lower reaches of the Amur River and the Amursky Liman, 17 morphologically intermediate individuals (hybrids) with the body length of 56 to 202 cm (median, 81 cm) were identified, including 11 individuals (4.6%) found in 2009, three individuals (1.6%) found in 2010, and three individuals (1.1%), in 2011. In 16 hybrids 819 bp of the mtDNA control regions were sequences and 11 haplotypes were identified. Since all these haplotypes were from the mtDNA lineages of kaluga, it was concluded that hybridization occurred in one direction, kaluga (?) x Amur sturgeon (?). This asymmetry could be caused by the large difference in sizes of these species. Since the earlier examined morphologically typical Amur sturgeons showed the absence of alien haplotypes (Shedko, et al., 2015), the absence of the mtDNA introgression is claimed. This can be caused by low viability or sterility of the backcross females (kaluga (?) x Amur sturgeon (?)) x Amur sturgeon (?). The samples of hybrids and typical kaluga individuals demonstrated no differences in the frequency spectra of the mtDNA haplotypes. However, haplotype and nucleotide diversity in the first sample was somewhat higher than in the second one (0.950 versus 0.927 and 0.0054 versus 0.0044, respectively). The data obtained will be useful for population monitoring of kaluga and Amur sturgeon, Amur River endemics, which are classified as critically endangered by the IUCN Red List of Threatened Species. PMID- 27281854 TI - [Expression of SM30 (A-F) Genes Encoding Spicule Matrix Proteins in Intact and Damaged Sea Urchin Strongylocentrotus intermedius (A. Agassiz, 1863) at the Six Arm Pluteus]. AB - In this study we investigated expression of the SM30(A-F) gene family encoding Strongylocentrotus intermedius spicule matrix proteins during the normal and regenerative pluteus II stage (three pairs of arms). We found that SiSM30A and SiSM30B genes are expressed at high levels in the normal pluteus II sea urchin. SiSM30A is expression was also significantly upregulated in the reparative pluteus II stage 3 hours after damage. Conversely, SiSM30B was downregulated during the reparative pluteus II stage. Our findings reveal a substantial similarity between the activity of SiSM30A and SiSM30B activity in the processes of regenerative growth during the pluteus II stage and during normal development at the prism stage in Strongylocentrotus purpuratus. On the basis of our findings, we propose that normal developmental mechanisms corresponding to the preceding developmental stage are reactivated during pluteus regeneration. PMID- 27281855 TI - [Comparative Estimate of the Sheep Breed Gene Pools using ISSR Analysis]. AB - Using the ISSR-PCR technique, the genetic structure of nine sheep breeds (Ovis aries) bred on the territories of Russia and Mongolia was examined. Species specific and breed-specific DNA fragments were identified. For the first time, data on the genetic diversity of Telengit and Buubey sheep breeds were obtained. The main parameters of the genetic diversity and the breed structure were assessed, and the phylogenetic relationships and genetic distances between the studied breeds were determined. Using the method of hierarchical frequency averaging, the prototypal sheep gene pool was reconstructed. The three-tiered analysis of diversity based on the ISSR fingerprinting data showed that 15.8% of variability was found between the breeds, 31.4% of variability was found between the populations within the breeds, and the diversity among the individuals within the populations constituted 52.8%. PMID- 27281856 TI - [Variability of the mtDNA Control Region in Goose Anser albifrons Scopoli, 1769]. AB - Sequence variation of the mtDNA (D loop) control region was examined in greater white-fronted goose Anser albifrons Scopoli, 1769 individuals (n = 71). The obtained sequences were compared with those from the NCBI GenBank database. The high level of similarity of the sample from Primorye (A. albifrons) with the sample from Japan (A. a. frontalis) at the level of molecular variation, genetic distance, phylogenetic reconstruction, and haplotype network was demonstrated. A hypothesis on the ways of spring goose migration in the Far East was made. It was confirmed that white-fronted geese wintering in Japan fly to their breeding grounds through Kamchatka. PMID- 27281857 TI - [Role of Allelic Genes of Matrix Metalloproteinases and Their Tissue Inhibitors in the Peptic Ulcer Disease Development]. AB - Peptic ulcer disease is a chronic disease of the gastrointestinal tract, mainly manifesting itself in the formation of the fairly persistent ulcer defect of the mucous membrane of the stomach and/or duodenum. Association analysis of common polymorphisms of matrix metalloproteinases genes MMP-1 (rs1799750, rs494379), MMP 2 (rs2285052), MMP-3 (rs3025058), MMP-9 (rs3918242, rs17576), and MMP-12 (rs2276109) and their tissue inhibitors TIMP-2 (rs8179090) and TIMP-3 (rs9619311) was carried out in 353 patients with a gastric ulcer or duodenal ulcer and in 325 unrelated healthy individuals from the Republic of Bashkortostan. Associations of polymorphic variants rs1799750 and rs494379 of gene MMP-1, rs3025058 of gene MMP 3, rs3918242 and rs17576 of gene MMP-9, and rs9619311 of gene TIMP-3 with the risk of peptic ulcer disease in Russians and Tatars were revealed. PMID- 27281858 TI - [Haplotype Analysis of Oculopharyngeal Muscular Dystrophy (OPMD) Locus in Yakutia]. AB - Oculopharyngeal muscular dystrophy (OPMD) is a hereditary neuromuscular disease with autosomal dominant and rarely with autosomal recessive inheritance types. This study included 50 patients with a clinical diagnosis of OPMD, 23 asymptomatic carriers of the mutation from 45 unrelated families, and 56 healthy relatives, as well as population samples of four ethnic groups of Yakutia: Yakuts, Evens, Evenks, Yukaghirs. It was found that the cause of OPMD development in all investigated families is the same increase in.GCN repeats to 14 copies in the PABPN1 gene. The molecular structure ofthe (GCN)14 mutant allele is (GCG)10(GCA)3GCG. The genetic variability of ten SNPs at the OPMD locus was studied in patient families and population samples. The haplotypes of OPMD were determined by a segregation analysis technique using the EM algorithm in the groups of patients, mutation carriers, and population samples. Only one haplotype of four SNPs (ATCG) linked with the (GCN)14 mutant allele was found in Yakuts and Russian patients and OPMD mutation carriers. Probably, this indicates the accumulation of mutations as a result of the founder effect. PMID- 27281859 TI - [Marriage and Migratory Characteristic of Circassians (Late 20th Century)]. AB - This paper analyzes 2052 marriage records for 1990-2000 in the Khabezsky district of Karachay-Cherkessia. The main marriage and migration characteristics of Circassians are studied: index of endogamy, ethnic mar- riage assortativity, intensity of metisation, and Malecot's parameters of isolation by distance. PMID- 27281860 TI - Nursing in Urology: Where Can We Go from Here? PMID- 27281861 TI - Genitourinary Syndrome Of Menopause and Vaginal Estrogen Use. AB - The prevalence of women experiencing the genitourinary syndrome of menopause is expected to escalate due to the rising numbers of menopausal women. In no other time in history has it been more important for nurses to possess current knowledge regarding menopause management. PMID- 27281862 TI - Effect of an Education Presentation On the Knowledge and Awareness of Urinary Tract Infection among Non-Licensed and Licensed Health Care Workers in Long-Term Care Facilities. AB - This article presents the findings of a pre-test, post-test quality improvement project that describes the change in knowledge from prior to and following an evidence-based education presentation. The presentation addressed the clinical symptoms, diagnostic processes, interventions, and responsibilities of licensed and unlicensed health care workers employed in long-term care facilities related to prevention and detection of non-catheter-related urinary tract infections. Results indicate that the education presentation improved knowledge in specific. PMID- 27281863 TI - Application to the Evidence Base: Effect of an Education Intervention on Urinary Tract Infection Knowledge. PMID- 27281864 TI - Anesthetic Concerns for Patients Undergoing a Transurethral Resection of the Prostate (TURP). AB - Although there are competing alternatives available to treat benign prostatic hyperplasia (BPH), transurethral resection of the prostate (TURP) remains the gold standard using either general or spinal anesthesia. There are advantages and disadvantages related to spinal or general anesthesia. Anesthetic concerns and complications during the preoperative, intraoperative, and postoperative surgical phases are analyzed and summarized. Early detection and prevention play a key role in reducing complications and shortening the recovery period. PMID- 27281865 TI - Pelvic Muscle Exercises Using A Home Trainer for Pelvic Muscle Dysfunction: A Case Report. AB - Pelvic muscle exercises can help improve symptoms of pelvic floor muscle dysfunction. This article describes the case of a 66-year-old woman with moderate pelvic organ prolapse (POP) and mild urinary incontinence (UI) who initiated pelvic muscle exercises with the assistance of a novel, at-home trainer equipped with a vaginal sensor and accompanying smartphone app software, the PeriCoach system (Analytica, 2015). After 8 weeks of training with the device, she showed improvements in strength, endurance, and disability, as measured by manual muscle test, electromyography, and Pelvic Floor Disability Index scores. Older women can use biofeedback technology to improve pelvic floor muscle function successfully at home. PMID- 27281866 TI - Pelvic Floor Biofeedback via a Smart Phone App for Treatment Of Stress Urinary Incontinence. AB - Biofeedback can be useful for treatment of stress urinary incontinence. Many women have difficulty isolating their pelvic floor muscles and adhering to a daily exercise regimen. This case study highlights a woman's experience using PeriCoach, a home biofeedback device that assists women in strengthening their pelvic floor muscles through Bluetooth technology using a smartphone. PMID- 27281867 TI - Chasing Zero: A Nurse-Driven Process for Catheter-Associated Urinary Tract Infection Reduction In a Community Hospital. AB - Due to treatment costs and lack of reimbursement, community hospitals are charged with implementing innovative strategies that will reduce the incidence of hospital-acquired catheter-associated urinary tract infections (CAUTI). A nurse driven system for decreasing the number of hospital-acquired CAUTI is effective and useful for a community hospital. One nurse with accountability for implementing a simple evidence-based protocol can dramatically decrease the total incidence of hospital-acquired CAUTI. The basis for the success of this initiative relied heavily on the ease of using the eight-point Question the Foley criteria, the availability of the electronic medical record, interdisciplinary collaboration, and support from nursing and physician administration. With collaboration and support from nursing leadership, the goals for patient safety by reducing hospital-acquired CAUTI can become a reality in a short period of time. PMID- 27281868 TI - Evidence-Based Nursing: When the Evidence Is Fraudulent. PMID- 27281869 TI - [EFFECTS OF BONE MARROW MESENCHYMAL STEM CELLS TRANSPLANTATION FOR TREATING RAT SPINAL CORD INJURY AND CYTOKINE EXPRESSION AT INJURY SITES]. AB - OBJECTIVE: To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) transplantation for treating spinal cord injury (SCI) in rat and the cytokine expression changes in the local injury tissues. METHODS: BMSCs were separated from Sprague Dawley (SD) rat and cultured with the whole bone marrow culture method. rAd-EGFP was used to transfect the 5th generation BMSCs for green fluorescent protein (GFP) label. Twelve SD rats were randomly divided into experimental group (n = 6) and control group (n = 6). After the T10 SCI model was established with Allen's impact device in 2 groups, 1 x 1096) GFP-labeled BMSCs and PBS were administered by subarachnoid injection in situ in experimental group and control group, respectively. Basso-Beattie-Bresnahan (BBB) score was used to detect the motor function at immediat, 1, 2, 3, 4, and 5 weeks after SCI. At 5 weeks, the spinal cord tissues were harvested for the histological and immunofluorescent staining examinations to measure the expressions of neural marker molecules, including Nestin, glial fibrillary acidic protein (GFAP), and neuron-specific nuclear protein (NeuN). Cytokine was analyzed with antibody array. RESULTS: At 5 weeks, 2 rats died of urinary tract infection in 2 groups respectively, the other rats survived to the end of experiment. BBB score of experimental group was significantly higher than that of control group at 1, 2, 3, 4, and 5 weeks (P < 0.05). At 5 weeks, histological results showed that there were many cells with regular arrangement in the experimental group; there were less cells with irregular arrangement in the control group. Compared with the control group, Nestin and NeuN expressions significantly increased (P < 0.05), and GFAP expression significantly decreased (P < 0.05) in the experimental group. Leptin and ciliary neurotrophic factor levels were higher in the experimental group than the control group, but granulocyte-macrophage colony-stimulating factor, tumor necrosis factor beta, interleukin 1 beta, and tissue inhibitor of metalloproteinases 1 levels were lower in the experimental group than the control group. CONCLUSION: BMSCs transplantation can improve survival and regeneration of nerve cells and enhances the recovery of nerve function by regulating secretion of cytokines from grafted BMSCs. PMID- 27281870 TI - [EFFECT OF Hey1 EXPRESSION ON OSTEOGENIC DIFFERENTIATION AND PROLIFERATION OF C3H10T1/2 CELLS INDUCED BY BONE MORPHOGENETIC PROTEIN 9]. AB - OBJECTIVE: To investigate the effect of Notch signaling pathway important target Hey1 expression on the differentiation and proliferation of C3H10T1/2 cells induced by bone morphogenetic protein 9 (BMP-9). METHODS: Hey1 lentivirus and Hey1 short hairpin RNA lentivirus were constructed and used to infect C3H10T1/2 cells to change the expression level of Hey1 in C3H10T1/2 cells. C3H10T1/2 cells infected with LV-Blank (empty plasmid) as control. The Hey1 expression levels of different groups were detected by fluorescence microscope, real-time fluorescence quantitative PCR, and Western blot. The C3H10T1/2 cells with different Hey1 expression level were induced by BMP-9 conditioned medium (BMP-9+C3H10T1/2 group, BMP-9+C3H10T1/2-Hey1 group, and BMP-9+C3H10T1/2-shHey1 group); the cells of control groups (C3H10T1/2 group and G3H10T1/2-Blank group) were cultured with normal medium. The mRNA and protein expression levels of osteogenesis related transcription factors (Runx2, osteopontin, and osteocalcin) were detected at 48 hours by real-time fluorescence quantitative PCR and Western blot assay. The cells proliferation and cycles were detected by MTT assay at 4, 5, 6, and 7 days and flow cytometry at 4, 5, and 10 days. The alkaline phosphatase (ALP) activity was analyzed by ELISA and observed by ALP staining at 4 and 7 days. RESULTS: C3H10T1/2 cell lines with different Hey1 expression levels were successfully established. In osteogenesis compared with BMP-9+C3H10T1/2 group, overexpression of Hey1 enhanced the mRNA and protein expressions of transcription factors (Runx2, osteopontin, and osteocalcin), and the expression of osteogenic differentiation marker (ALP) (P < 0.05); however, inhibition of Hey1 expression significantly decreased the above indexes (P < 0.05). In cell proliferation activity compared with BMP-9+C3H10T1/2 group, overexpression of Hey1 increased absorbance (A) value in MTT assay and pecentage of G2+S cells in cytometry assay, but inhibition of Hey1 expression significantly decreased the indexes (P < 0.05). CONCLUSION: Expression of Hey1 is the important link in the osteogenic differentiation process of C3H10T1/2 cells induced by BMP-9, and plays an important role in the regulation of early cell proliferation. PMID- 27281871 TI - [ECTOPIC OSTEOGENESIS EVALUATION OF RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN 2 LOADED CHITOSAN/DEXTRAN SULFATE BY MICRO-CT]. AB - OBJECTIVE To evaluate the ectopic osteogenesis of recombinant human bone morphogenetic protein 2 (rhBMP-2) loaded chitosan (CS)/dextran sulfate (DS) by micro-CT. METHODS: rhBMP-2/CS/DS microspheres were prepared by the ionic crosslinking and its shape was observed under the scanning electron microscope. The release of rhBMP-2 was determined from resultant microspheres by ELISA assay. Forty-eight Sprague Dawley male rats were randomly divided into 4 groups (n = 12), quadriceps muscle bag model was made, gelatin sponge (group A), CS/DS microspheres (group B), rhBMP-2 (group C), and CS/DS/rhBMP-2 microspheres (group D) were implanted into the bags respectively. The tissue samples with heterotopic ossification were harvested for micro-CT scanning at 4, 8, 12, and 16 weeks. The tissue mineral density (TMD), bone volume fraction (BVF), trabecular thickness (Tb.Th), trabecular number (Tb.N), bone mineral density (BMD), and tissue mineral content (TMC) were measured. RESULTS: The prepared rhBMP-2/CS/DS microspheres with smooth surfaces were spherical and evenly disperses without obvious agglomeration. At 2 hours, microsphere started a sudden release period in vitro; the release reached a peak at 2 days; and the release cycle lasted about 20 days. The rats survived to the end of the experiment. At each time point after operation, no radiation developed and no osteogenesis was observed by three dimensional reconstruction in groups A and B. However, radioactive strength and reconstructed bone tissue gradually increased in groups C and D, and group D had more radioautography and more bone tissues than group C. At each time point, TMD, BVF, Tb.Th, Tb.N, BMD, and TMC of groups A and B were zero. Ectopic bone formed with time, the other parameters showed an increasing trend except Tb.N in groups C and D, showing significant difference when compared with groups A and B at each time point (P < 0.05). There was no significant difference between groups C and D at 4 weeks (P > 0.05); the parameters of group D were significantly higher than those of group C at 8-16 weeks (P < 0.05). CONCLUSION: rhBMP-2/CS/DS microspheres have stronger ability of ectopic bone formation than single rhBMP-2. PMID- 27281872 TI - [CYTOCOMPATIBILITY AND PREPARATION OF BONE TISSUE ENGINEERING SCAFFOLD BY COMBINING LOW TEMPERATURE THREE DIMENSIONAL PRINTING AND VACUUM FREEZE-DRYING TECHNIQUES]. AB - OBJECTIVE: To study the preparation and cytocompatibility of bone tissue engineering scaffolds by combining low temperature three dimensional (3D) printing and vacuum freeze-drying techniques. METHODS: Collagen (COL) and silk fibroin (SF) were manufactured from fresh bovine tendon and silkworm silk. SolidWorks2014 was adopted to design bone tissue engineering scaffold models with the size of 9 mm x 9 mm x 3 mm and pore diameter of 500 MUm. According to the behavior of composite materials that low temperature 3D printing equipment required, COL, SF, and nano-hydroxyapatite (nHA) at a ratio of 9 : 3 : 2 and low temperature 3D printing in combination with vacuum freeze-drying techniques were accepted to build COL/SF/nHA composite scaffolds. Gross observation and scanning electron microscope (SEM) were applied to observe the morphology and surface structures of composite scaffolds. Meanwhile, compression displacement, compression stress, and elasticity modulus were measured by mechanics machine to analyze mechanical properties of composite scaffolds. The growth and proliferation of MC3T3-E1 cells were evaluated using SEM, inverted microscope, and MTT assay after cultured for 1, 7, 14, and 21 days on the composite scaffolds. The RT-PCR and Western blot techniques were adopted to detect the gene and protein expressions of COL I, alkaline phosphatase (ALP), and osteocalcin (OCN) in MC3T3-E1 cells after 21 days. RESULTS: COL/SF/nHA composite scaffolds were successfully prepared by low temperature 3D printing technology and vacuum freeze-drying techniques; the SEM results showed that the bionic bone scaffolds were 3D polyporous structures with macropores and micropores. The mechanical performance showed that the elasticity modulus was (344.783 07 +/- 40.728 55) kPa; compression displacement was (0.958 41 +/- 0.000 84) mm; and compression stress was (0.062 15 +/- 0.007 15) MPa. The results of inverted microscope, SEM, and MTT method showed that a large number of cells adhered to the surface with full extension and good cells growth inside the macropores, which demonstrated a satisfactory proliferation rate of the MC3T3-E1 cells on the composite scaffolds. The RT-PCR and Western blot electrophoresis revealed gene expressions and protein synthesis of COL I, ALP, and OCN in MC3T3-E1 cells. CONCLUSION: Low temperature 3D printing in combination with vacuum freeze-drying techniques could realize multi-aperture coexisted bionic bone tissue engineering scaffolds and control the microstructures of composite scaffolds precisely that possess good cytocompatibility. It was expected to be a bone defect repair material, which lays a foundation for further research of bone defect. PMID- 27281873 TI - [EXPERIMENTAL STUDY ON CHITOSAN/ALLOGENEIC BONE POWDER COMPOSITE POROUS SCAFFOLD TO REPAIR BONE DEFECTS IN RATS]. AB - OBJECTIVE: To explore the feasibility of chitosan/allogeneic bone powder composite porous scaffold as scaffold material of bone tissue engineering in repairing bone defect. METHODS: The composite porous scaffolds were prepared with chitosan and decalcified allogeneic bone powder at a ratio of 1 : 5 by vacuum freeze-drying technique. Chitosan scaffold served as control. Ethanol alternative method was used to measure its porosity, and scanning electron microscopy (SEM) to measure pore size. The hole of 3.5 mm in diameter was made on the bilateral femoral condyles of 40 adult Sprague Dawley rats. The composite porous scaffolds and chitosan scaffolds were implanted into the hole of the left femoral condyle (experimental group) and the hole of the right femoral condyle (control group), respectively. At 2, 4, 8, and 12 weeks after implantation, the tissues were harvested for gross observation, histological observation, and immunohistochemical staining. RESULTS: The composite porous scaffold prepared by vacuum freeze-drying technique had yellowish color, and brittle and easily broken texture; pore size was mostly 200-300 MUm; and the porosity was 76.8% +/- 1.1%, showing no significant difference when compared with the porosity of pure chitosan scaffold (78.4% +/- 1.4%) (t = -2.10, P = 0.09). The gross observation and histological observation showed that the defect area was filled with new bone with time, and new bone of the experimental group was significantly more than that of the control group. At 4, 8, and 12 weeks after implantation, the bone forming area of the experimental group was significantly larger than that of the control group (P < 0.05). The immunohistochemical staining results showed that osteoprotegerin (OPG) positive expression was found in the experimental group at different time points, and the positive expression level was significantly higher than that in the control group (P < 0.05). CONCLUSION: Chitosan/allogeneic bone powder composite porous scaffold has suitable porosity and good osteogenic activity, so it is a good material for repairing bone defect, and its bone forming volume and bone formation rate are better than those of pure chitosan scaffold. PMID- 27281874 TI - [EXPERIMENTAL STUDY ON THREE DIMENSINONAL CULTURE OF RABBIT ANNULUS FIBROSUS CELLS ON KLD-12 POLYPEPTIDE NANOFIBER GEL IN VlTRO]. AB - OBJECTIVE: To investigate the feasibility to culture rabbit annulus fibrosus cells on the KLD-12 polypeptide nanofiber gel so as to search for the seed cells and the scaffolds for tissue engineering. METHODS: The rabbit annulus fibrosus cells were isolated with pancreatin and cultured; the cells at passage 3 were seeded on the KLD-12 polypeptide nanofiber gel to prepare the KLD-12 polypeptide/annulus fibrosus cells gel. The cell morphology change was observed by inverted microscope. The cell counting kit 8 (CCK-8) was used to detect the cell proliferation, and Calcein-AM/propidium iodide (PI) fluorescent staining to observe the cell vitality. The alcian blue method was used to measure the glycosaminoglycan (GAG) content, immunofluorescence technique to observe the collagen type II level, and real-time fluorescence quantitative PCR (RT-qPCR) to measure the mRNA expressions of Aggrecan and collagen type II. RESULTS: The cells on the scaffolds grew well, showing round shape on the scaffolds and spindle or fusiform shape at the edge of the scaffold. The cell proliferation exhibited increasing trend with time, and it was significantly higher at 14 days than the other time points (P < 0.05), and on KLD-12 polypeptide nanofiber gel than on blank gel (P < 0.05). The ratios of living cells were 89.32% +/- 8.58% at 5 days and 97.81% +/- 1.09% at 14 days, showing no significant difference (t = - 1.962, P = 0.097). The GAG content gradually increased with culture time, reached the peak at 8 days, and then gradually decreased; the GAG content at 5, 8, and 11 days was significantly higher than that at 2 and 14 days (P < 0.05). The level of collagen type II was normal. The mRNA expressions of collagen type II and Aggrecan could be measured at 5 and 14 days; the relative expression levels of collagen type II and Aggrecan mRNA were significantly higher at 14 days than 5 days (P < 0.05). CONCLUSION: The rabbit annulus fibrosus cells on KLD-12 polypeptide nanofiber gel are able to grow well and to produce extracellular matrix, so KLD-12 polypeptide nanofiber gel has the potential to serve as a scaffold for the treatment of intervertebral disc degeneration. PMID- 27281875 TI - [CONSTRUCTION OF TISSUE ENGINEERED COMPOSITE WITH THERMOSENSITIVE COLLAGEN HYDROGEL IN DYNAMIC CULTURE SYSTEM]. AB - OBJECTIVE: To explore the morphological and functional features of tissue engineered composite constructed with bone mesenchymal stem cells (BMSCs) as seeding cells, thermosensitive collagen hydrogel (TCH) and poly-L-lactic acid (PLLA) as the extracellular matrix (ECM) scaffolds in the dynamic culture system. METHODS: BMSCs were separated from long bones of Fischer 344 rat, and cultured; and BMSCs at the 3rd generation were seeded on the ECM scaffold constructed with braided PLLA fiber and TCH. The BMSCs-ECM scaffold composite was cultured in the dynamic culture system which was designed by using an oscillating device at a frequency of 0.5 Hz and at swing angle of 70 degrees (experimental group), and in the static culture system (control group) for 7 days. The general observation and scanning electron microscopy (SEM) observation were performed; total DNA content was.measured at 0, 1, 3, and 7 days. RESULTS: PLLA was surrounded by collagen to form translucent gelatiniform in 2 groups; and compact membrane developed on the surface of PLLA. SEM observation showed that BMSCs had high viability and were fusiform in shape with microvilli on the surface of cells, and arranged in line; collagen and cells filled in the pores of PLLA fiber in the experimental group. The cells displayed a flat shape on the surface; there were less cells filling in the pores of PLLA fiber in the control group. At 1, 3, and 7 days, total DNA content in the experimental group was significantly higher than that in control group (P < 0.05). The total DNA content were increased gradually with time in 2 groups, showing significant difference between at 0 day and at 7 days (P < 0.05). CONCLUSION: The ECM constructed with TCH and PLLA has good biocompatibility. The dynamic cultivation system can promote the cell proliferation, distribution, and alignment on the surface of the composite, so it can be used for tissue engineered composite in vitro. PMID- 27281876 TI - [RESEARCH AND PROSPECT OF MESENCHYMAL STEM CELLS IN FEMALE FERTILITY PRESERVATION]. AB - OBJECTIVE: Fertility preservation (FP) technology has gradually been concerned by scholars all over the world due to the increasing survival rate of cancer patients. To review the recent progress of mesenchymal stem cells (MSCs) in female FP. METHODS: The recent original literature about MSCs in female FP was extensively reviewed. RESULTS: MSCs have the advantages of rich source, easy isolation and amplification, and capacities for multipotential differentiation and migration so that they can be used to avoid the ethical and legal controversy which have great potential of FP for the damage of ovarian tissue and reproductive endocrine disorders. In addition, MSCs can be induced to differentiate into a specific condition, which is expected to be the resource in oocyte-like cells that can be used as a steady cell source for the future experiments and clinical application. CONCLUSION: MSCs have great potential to provide new research ideas for future FP technology. PMID- 27281877 TI - [RESEARCH PROGRESS OF ADIPOSE-DERIVED STEM CELLS COMPOUND WITH THREE DIMENSIONAL PRINTING SCAFFOLD FOR ENGINEERED TISSUE]. AB - OBJECTIVE: To review the research progress of adipose-derived stem cells (ADSCs) compound with three dimensional (3D) printing scaffold in tissue engineering of fat, bone, cartilage, blood vessel, hepatocyte, and so on. METHODS: The recently published literature about ADSCs compound with 3D printing scaffold in tissue engineering at home and abroad was reviewed, analyzed, and summarized. RESULTS: A large number of basic researches showed that ADSCs could differentiate into a variety of tissues on 3D printing scaffold and involve in tissue repair and regeneration. But there is still a long way between the basic theory and the clinical practice at the early stages of development. CONCLUSION: It can effectively improve and restore the structure and function of the damaged tissue and organ to use ADSCs and 3D printing scaffold. PMID- 27281878 TI - [RESEARCH PROGRESS OF TISSUE ENGINEERING TECHNIQUE IN ESOPHAGEAL DEFECT REPAIR AND RECONSTRUCTION]. AB - OBJECTIVE: To review the research progress of the tissue engineering technique in the esophageal defect repair and reconstruction. METHODS: The recently published clinical and experimental literature at home and abroad on the scaffold materials and the seeding cells used in the tissue engineered esophageal reconstruction was consulted and summarized. RESULTS: A large number of basic researches and clinical applications show that the effect of the tissue engineered esophagus is close to the autologous structure and function of the esophagus and it could be used for the repair of the esophageal defect. However, those techniques have a long distance from the clinical application and need an acknowledged rule of technology. CONCLUSION: Tissue engineering technique could provide an innovative theory for the esophageal defect reconstruction, but its clinical application need further research. PMID- 27281879 TI - [PRELIMINARY EFFECTIVENESS OF POLYAMINOACID/NANO-HYDROXYAPATITE/CALCIUM SULFATE CAGE IN LUMBAR FUSION SURGERY]. AB - OBJECTIVE: To discuss the early effectiveness of polyaminoacid/nano hydroxyapatite/calcium sulfate (PAA/HA/CS) Cage (PHC Cage) in lumbar fusion surgery. METHODS: Thirty cases undergoing lumbar fusion of single segment between March and September 2014 were enrolled in this study. The patients were randomly divided into the trial group (n = 20) and the control group (n = 10). The PHC Cage was implanted in the trial group, while the polyetheretherketone (PEEK) Cage was implanted in the control group. The patients of 2 groups mainly presented lumbocrural pain and lower limb radiation pain or numbness. There was no significant difference in gender, age, type, affected segment, disease duration, preoperative intervertebral height, the lordosis angle of fusion segments, and the Oswestry Disability Index (ODI) between 2 groups (P > 0.05). Lateral lumbar X ray films and three dimensional CT were taken preoperatively and at 1 week and 3, 6, and 12 months postoperatively. The intervertebral height and the lordosis angle of fusion segments at 1 week and 3, 6, and 12 months after operation and ODI at 3, 6, and 12 months after operation were measured; and the bone graft fusion rate was evaluated according to Brantigan criteria. RESULTS: There was no significant difference in operation time, intraoperative blood loss, and the amount of autologous blood transfusion between 2 groups (P > 0.05). Healing by first intention as obtained in 30 cses. All patients were followd up 12 months. The intervertebral height of fusion segments, the lordosis angle of fusion segments, and ODI at each time point after operation were significantly improved when compared with preoperative ones (P < 0.05). The ODI showed significant difference between 3 months and 6, 12 months (P < 0.05), but there was no significant difference between the other time points after operation (P > 0.05). There was no significant difference in the intervertebral height and the lordosis angle of fusion segments between groups at different time points (P > 0.05). There was no significant difference in the above indexes between the trial group and the control group at each time point (P > 0.05). At last follow-up, 5 cases were rated as Brantigan grade E, 13 cases as grade D, and 2 cases as grade C in the trial group; 4 cases were rated grade E, 5 cases as grade D, and 1 case as grade C in the control group. The bone fusion rate was 90% in 2 groups. CONCLUSION: The PHC Cage can effectively restore and maintain the disc height of fusion segment, normal sequence and biomechanical stability of the lumbar spine. The PHC Cage is similar to the PEEK Cage and has good clinical outcome in short term follow-up. PMID- 27281880 TI - [CHANGE AND CLINICAL SIGNIFICANCE OF CERVICAL SPINE SAGITTAL ALIGNMENT OF ADOLESCENT IDIOPATHIC SCOLIOSIS]. AB - OBJECTIVE: To investigate the changes and relationship of cervical spine sagittal alignment and other spinal-pelvic sagittal parameters in adolescent idiopathic scoliosis. METHODS: Between July 2011 and July 2014, 35 patients with idiopathic scoliosis who met the inclusion criteria underwent posterior pedicle screw instrumentation and fusion. There were 12 males and 23 females with a mean age of 16.2 years (range, 13-20 years), including 16 cases of Lenke type 1, 7 cases of Lenke type 2, 4 cases of Lenke type 3, 3 cases of Lenke type 4, 4 cases of Lenke type 5, and 1 case of Lenke type 6. The average follow-up time was 10.9 months (range, 5-36 months). The pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), cervical lordosis (CL), T1 slope, C2 slope, C7 sagittal vertical axis (C7 SVA), C2.7 plumbline (cSVA) were measured on pre- and post-operative standing lateral X-ray film. Based on preoperative CL, the patients were divided into kyphosis group (CL > 0 degress) and lordosis group (CL < 0 degrees); after operation, the patients were divided into restored lordosis (group A), decreased kyphosis (group B), and increased lordosis (group C) after operation. All data about sagittal profile changes were analyzed. The relations between CL and other spinal-pelvic parameters in the kyphosis and lordosis groups before operation were determined via Spearman correlation coefficient. RESULTS: Statistically significant changes were observed in PT, PI, SS, and LL between at pre- and post-operation (P < 0.05), but no significant difference was found in the other parameters (P > 0.05). There were 17 patients in lordosis group and 18 in kyphosis group before operation. Intra group comparisons showed significant changes in PT, PI, SS, C2 slope, and C7 SVA in lordosis group, and in PT, PI, SS, LL, CL, TK, T1 slope, and C2 slope in kyphosis group (P < 0.05). Subgroup comparisons showed significant changes in CL, TK, C2 slope, C7 SVA, and T1 slope before operation (P < 0.05) and T1 slope at last follow-up between 2 groups (P < 0.05). In kyphosis group, 7 cases (group A) had restored lordosis, 7 cases (group B) had decreased kyphosis, and 4 cases had increased lordosis. In lordosis group, 9 cases (group C) had increased lordosis, 3 cases had decreased lordosis, and 5 cases had kyphotic cervical alignment after operation. Significant difference was found in LL, CL, T1 slope, C2 slope, and C7 SVA of group A, in TK and CL of group B, and in CL and cSVA of group C between pre- and post-operation (P < 0.05). There were significant differences in pre- and post-operative LL between groups A and B (P < 0.05). In lordosis group, there was a strong correlation between CL and C2 slope (P < 0.05) at preoperation. CL had strong correlation with C2 slope and T1 slope (P < 0.05) at pre-operation in kyphosis group, and CL had moderate correlation with cSVA (P < 0.05). CONCLUSION: Cervical sagittal alignment plays an important role in the balance of the spine and pelvis. The change of cervical sagittal alignment has a certain correlation with the change of thoracic kyphosis. Attention to properly maintaining or restoring cervical sagittal lordosis alignment should be considered in preoperative evaluation of adolescent indiopathic scoliosis. PMID- 27281881 TI - [ESTABLISHMENT OF INTERVERTEBRAL DISC DEGENERATION OF RABBITS BY USING MINIMALLY INVASIVE ACUPUNCTURE AND ROTARY-CUTTING]. AB - OBJECTIVE: To investigate the feasibility of establishing intervertebral disc degeneration (IDD) model by using minimally invasive acupuncture and rotary cutting. METHODS: Forty New Zealand white rabbits [male or female, (2.9 +/- 0.3) kg in weight] were randomly divided into control group (n = 20) and experimental group (n = 20). No treatment was done in the control group; percutaneous puncture was performed on L4,5 and L5,6 intervertebral disc by using 18G needle under C arm X-ray monitoring for rotary-cutting of nucleus pulposus to promote degeneration of the disc in the experimental group. At 4, 8, 12, and 16 weeks after operation, general observation and MRI observation were done, and intervertebral disc degeneration was accessed based on Pfirrmann grade; the specimens were harvested for Masson staining and Safranine O staining. RESULTS: The nucleus pulposus showed dark colors and reduced elasticity in the experimental group when compared with the control group. T2-weighted MRI images indicated that the disc signal intensity of control group had no obvious change at early stage, and weakened slightly at late stage; disc signal intensity of the experimental group decreased with time. According to Pfirrmann grade for disc degeneration, disc degeneration degree was significantly aggravated with time in 2 groups (P < 0.05); degeneration was significantly more severe in the experimental group than the control group at the other time points (P < 0.05) except 4 weeks (P > 0.05). Masson staining results showed that irregular arrangement of annulus with integrate structure was observed in the control group with time; the annulus of the experimental group arranged in disorder, or even disc fibrous circle rupture appeared with time. Safranin O staining showed that the nucleus pulposus cells reduced significantly in the experimental group, but did not in the control group. CONCLUSION: Minimally invasive acupuncture and rotary-cutting could successfully establish the IDD model in rabbits. PMID- 27281882 TI - [MINI TITANIUM PLATE FOR TREATMENT OF INTRACAPSULAR CONDYLAR FRACTURES]. AB - OBJECTIVE: To investigate the effectiveness of mini titanium plate for the treatment of intracapsular condylar fractures-type A. METHODS: Between March 2013 and July 2015, 22 cases (26 sides) of intracapsular condylar fractures-type A were treated with mini titanium plate through anterior auricular approach. There were 13 males and 9 females, aged from 16 to 32 years (mean, 22.7 years). The disease causes were traffic accident injury in 17 cases, falling injury in 4 cases, and heavy impact injury in 1 case. Five cases had intracapsular condylar fractures-type A only, and the other cases were accompanied with fractures of mandible, maxillary, or other part of jaw. All patients had different degrees of limitation of opening mouth, occlusal disorder, and joint pain, and the maximum opening was 5-16 mm (mean, 8.6 mm). All patients received surgical treatment within 2 to 9 days after injury (mean, 4 days). The clinical dysfunction index (DI) of Helkimo index was used to evaluate the mandibular motor function postoperatively. According to the 4 basic criterion of cure about mandibular condylar fractures by the international consensus conference in 1999, and maximal mouth opening by HE Dongmei et al., the surgical treatment effectiveness was evaluated. RESULTS: All wounds healed at stage I, with no infection or other complications. All 22 cases were followed up 5-8 months (mean, 6 months). At 1 week after operation, the coronal spiral CT and three-dimensional reconstruction showed that contraposition of fractures was good, and the condyles located in the articular fossa. At 6 months after operation, the maximum opening was 33-42 mm (mean, 35.7 mm). After operation, 3 cases showed the mandible deflected to the affected side when opening, and limited lateral motion. According to the DI evaluation method in Helkimo index, there were 7 sides of DI grade 0, 18 sides of DI grade I, and 1 side of DI grade II. Based on surgical treatment effect of intracapsular condylar fractures-type A, occlusion recovery was obtained in 19 cases (86.36%), maximum opening degree of >= 35 mm in 20 cases (90.91%), no symptoms of joint injury in 19 cases (86.36%), and no serious postoperative complications in 22 cases (100%); 17 cases (77.27%) were in accordance with the above 4 items. CONCLUSION: Mini titanium plate is one of the most effective approaches to treat intracapsular condylar fractures-type A. PMID- 27281883 TI - [MODIFIED CLASSIFICATION AND MANAGEMENT OF TERRIBLE TRIAD OF ELBOW]. AB - OBJECTIVE: To investigate the feasibility of modified classification of terrible triad of the elbow and the effectiveness of treatment strategy which was chosen by modified classification results. METHODS: Between March 2007 and November 2013, 12 cases of terrible triad of the elbow were treated by operation. There were 5 males and 7 females with an average age of 37.2 years (range, 26-74 years). The mechanism of injury was falling from height in 8 cases and traffic accident in 4 cases. The time from injury to operation was 4 to 11 days (mean, 6.8 days). According to the radial head, coronoid process, olecranon, and medial and lateral collateral ligament complexes injury situation, and based on Mason classification standard and O'Driscoll criteria, the classification standard of terrible triad of the elbow was improved. According to classification results, the approach was determined. The fracture reduction and fixation were performed and soft tissue was repaired. RESULTS: Dehiscence of incision occurred in 1 case and was cured after dressing change; primary healing was obtained in the other patients. All the cases were followed up 19-35 months (mean, 21.6 months). The X ray films showed fracture healing at 10-17 weeks (mean 12.8 weeks). At last follow-up, the mean flexion-extension arc of the elbow was 117.9 degrees (range, 95-135 degrees) and the mean forearm pronation and supination were 77.1 degrees (range, 70-85 degrees) and 62.5 degrees (range, 45-75 degrees). According to Mayo elbow performance score (MEPS), the results were excellent in 4 cases, good in 5 cases, and fair in 3 cases. One patient had valgus deformity of elbow who refused radial head replacement, and 5 cases had heterotopic ossification of the elbow on the X-ray films. CONCLUSION: The modified classification of the terrible triad of the elbow is simple and practical, based on the damage assessment of bony structures (radial head, coronoid process, and olecranon) and the soft tissue (medial and lateral collateral ligament complexes). The modified classification can be used effectively for guiding treatment decisions. PMID- 27281884 TI - [EFFECTIVENESS OF OPEN REDUCTION AND INTERNAL FIXATION WITH LOCKING ANATOMICAL PLATE FOR TREATING VALGUS IMPACTED PROXIMAL HUMERUS FRACTURE]. AB - OBJECTIVE: To investigate the effectiveness of open reduction and internal fixation with locking anatomical plate for treating valgus impacted proximal humerus fracture. METHODS: A retrospective analysis was made on the clinical data of 38 patients with valgus impacted proximal humerus fracture who underwent open reduction and internal fixation with locking anatomical plate between January 2009 and January 2014. There were 25 males and 13 females, aged from 47 to 63 years (mean, 52.3 years); the left and the right sides were involved in 18 and 20 cases, respectively. The causes of fracture included high falling injury in 10 cases, traffic accident injury in 15 cases, and falling injury in 13 cases. The time between injury and operation was 5-10 days (mean, 7.5 days). The collodiaphyseal angle was 160-200 degrees (mean, 176 degrees) on X-ray films. RESULTS: All incisions healed by first intention, and there was no early complication related to operation. All these patients were followed up 12-30 months (mean, 18 months). X-ray film showed that clinical healing time of fracture was 10-16 weeks after operation (mean, 12 weeks); at 12 months after operation, the collodiaphyseal angle recovered to 120-145 degrees (mean, 135 degrees). During follow-up, no loss of fracture reduction and no loosening of internal fixation were observed. At 10-12 months, osteonecrosis of the humeral head occurred in 3 cases (7.9%), including 2 cases of Cruess stage III and 1 case of Cruess stage IV. At last follow-up, the Constant shoulder joint scores were 56 95 (mean, 82.6); the results were excellent in 10 cases, good in 15 cases, fair in 9 cases, and poor in 4 cases, with an excellent and good rate of 66%. Visual analogue scale (VAS) scores were 0-6 (mean, 0.9). CONCLUSION: It can achieve a comparatively satisfactory clinical result to use open reduction and internal fixation with locking anatomical plate for treating valgus impacted proximal humerus fracture. PMID- 27281885 TI - [EFFICACY COMPARISON BETWEEN DEEP MEDIAL COLLATERAL LIGAMENT REPAIR AND CONSERVATIVE TREATMENT FOR COMPLETE MEDIAL COLLATERAL LIGAMENT RUPTURE]. AB - OBJECTIVE: To compare the clinical efficacy between deep medial collateral ligament (dMCL) repair and conservative treatment for complete MCL rupture. METHODS: Between August 2009 and December 2013, 36 patients with grade 3 MCL rupture underwent superior MCL (sMCL) reconstruction with tibial Inlay technique. Of 36 cases, 19 received dMCL repair (repair group), and 17 received conservative treatment (conservation group) after sMCL reconstruction. There was no significant difference in gender, age, knee sides, type of injury, disease duration and preoperative medial joint opening, knee Lysholm scores, and International Knee Documentation Committee (IKDC) score between 2 groups (P > 0.05). The Lysholm and IKDC scores, medial joint opening, range of motion (ROM), visual analogue scale (VAS) scores, and complications were used to assess the knee joint function. RESULTS: All patients achieved primary incision healing without acute postoperative complications of incision infection and deep vein thrombosis in the lower limb. The patients were followed up 28-65 months (mean, 46.3 months) in the repair group, and 26-69 months (mean, 45.9 months) in the conservation group. No knee stiffness, vascular or nerve injury, and knee joint infection occurred in 2 groups. All the patients recovered medial stability at 2 years postoperatively. At 2 years after operation, no significant difference was shown in knee ROM between 2 groups (t = 0.26, P = 0.80); the VAS score of the repair group was significantly lower than that of the conservation group (t = 5.22, P = 0.00); medial joint opening, IKDC score, and Lysholm score were significantly improved when compared with preoperative ones in 2 groups (P<0.05), but no significant difference was found between 2 groups (P > 0.05). CONCLUSION: Whether or not additional dMCL repair is performed can recover medial stability after sMCL reconstruction. However, the additional dMCL repair is better in relieving medial knee pain than the conservative treatment. PMID- 27281886 TI - [[INFLUENCES OF PREOPERATIVE SEVERE LOWER LIMB DEFORMITY ON PROSTHESIS INSTALLATION AND ALIGNMENT RESTORATION IN TOTAL KNEE ARTHROPLASTY]. AB - OBJECTIVE: To investigate the effect of preoperative valgus or varus deformity on the prosthesis installation and alignment restoration in total knee arthroplasty (TKA). METHODS: Between January 2012 and December 2013, 198 patients (245 knees) with osteoarthritis underwent primary TKA, and the clinical data were retrospectively analyzed. There were 23 males and 175 females, with the average age of 67 years (range, 43-90 years). Single knee and double knees were involved in 151 and 47 cases respectively. The disease duration was from 1 month to 30 years (mean, 8.99 years). The anteroposterior X-ray films of whole lower limbs were taken, and the femorotibial angle (FT) was measured before operation and at 1 week after operation; the mechanical femoral angle (MF) and the anatomical tibial angle (AT) at 1 week after operation were measured. The correlation analysis was made for pre- and post-operative FT, MF, and AT. According to the valgus or varus deformity before operation, all patients were divided into 5 groups: >= 20 degrees varus (group A), 10-20 degrees varus (group B), <= 10 degrees varus (group C), < 10 degrees valgus (group D), and >= 10 degrees valgus (group E), and the above indicators were compared between groups. And the rate of the good limb alignment was recorded after operation. RESULTS: The pre- and post operative FT were (171.53 +/- 9.12) and (177.38 +/- 3.57)degrees respectively, and postoperative MF and AT were (89.00 +/- 2.68) and (88.62 +/- 2.16) respectively. Preoperative FT was associated with postoperative FT and MF (r = 0.375, P = 0.000; r = 0.386, P = 0.000), but it was not correlated with AT (r = 0.024, P = 0.710). Postoperative FT was associated with MF and AT (r = 0.707, P = 0.000; r = 0.582, P = 0.000). Postoperative FT was significantly increased when compared with preoperative FT in each group (P < 0.05). There were significant differences in preoperative FT between groups (P < 0.05). There were significant differences in postoperative FT when compared group A with groups B, C, D, and E (P < 0.05), and when compared groups B and C with groups D and E (P<0.05), but there was no significant difference between groups B and C, and between groups D and E (P > 0.05). The rate of good alignment was 70.2% (172/245); it was 27.8% (5/18), 66.0% (62/94), 74.4% (67/90), 88.9% (32/36), and 85.7% (6/7) in groups A, B, C, D, and E respectively, showing significant differences between groups (P < 0.05). There was no significant difference in postoperative AT between groups (P > 0.05). Except for between group D and group E (P > 0.05), significant difference in MF was shown between the other groups (P < 0.05). CONCLUSION: The more severe deformity of lower limb before TKA, the higher risk of deviation for prosthesis installation and poor alignment in TKA. PMID- 27281887 TI - [CLINICAL APPLICATION OF THREE DIMENSIONAL PRINTED NAVIGATION TEMPLATES FOR TREATMENT OF OSTEONECROSIS OF FEMORAL HEAD WITH PEDICLED ILIAC BONE GRAFT]. AB - OBJECTIVE: To investigate the feasibility and early effectiveness to treat osteonecrosis of the femoral head (ONFH) with pedicled iliac bone graft assisted by individual digital design and three dimensional (3D) printed navigation templates. METHODS: Between February and June 2014, 15 patients (24 hips) with ONFH underwent pedicled iliac bone graft assisted by individual digital design and 3D printed navigation templates. There were 11 males (17 hips) and 4 females (7 hips) with a mean age of 38 years (range, 18-56 years) and a mean disease duration of 7.5 months (range, 1-24 months); the left hip was involved in 2 cases, the right hip in 4 cases, and both hips in 9 cases. There were 7 cases (12 hips) of steroid-induced ONFH, 5 cases (8 hips) of alcohol-induced ONFH, 1 case (1 hip) of traumatic ONFH, and 2 cases (3 hips) of idiopathic ONFH. The preoperative Harris score was 56.60 +/- 6.97. According to Association Research Circulation Osseous (ARCO) staging system, 5 hips were classified as stage IIB, 8 hips as stage IIC, 6 hips as stage IIIB, and 5 hips as stage IIIC. The navigation templates were designed and printed to assist accurate location and debridement of necrosis area according to preoperative CT scanning at the beginning of pedicled iliac bone grafting procedure. RESULTS: The mean operation time was 135 minutes (range, 120-160 minutes), mean amount of bleeding was 255 mL (range, 200 300 mL). All the wounds healed primarily, no complication of deep vein thrombosis or infection was observed. All patients were followed up 12-16 months (mean, 14 months). The location of necrosis area was in accordance with preoperative design, which was removed completely without penetration of joint surface, pedicled iliac bone graft was performed at the right site according to postoperative imaging examination. Radiographically, graft fusion was achieved at 2.7 months (range, 2-3 months) in all patients. All the hips had no collapse during follow-up. Hip pain was relieved, and range of motion was improved. The Harris score was significantly improved to 89.53 +/- 5.83 at last follow-up (t = 14.3 19, P = 0.000). The results were excellent in 12 hips, good in 10 hips, and fair in 2 hips according to Harris score standard. CONCLUSION: Pedicled iliac bone graft assisted by individual digital design and 3D printed navigation templates for treatment of adult ONFH has the advantages of accurate location and complete debridement of necrosis area, so satisfactory results can be obtained. PMID- 27281888 TI - [FREE MEDIAL SURAL ARTERY PERFORATOR FLAP FOR REPAIRING ANTERIOR DORSAL FOOT WOUND]. AB - OBJECTIVE: To investigate the effectiveness of the free medial sural artery perforator flap for repairing anterior dorsal foot wound. METHODS: Between January 2010 and April 2015, 16 patients with skin and soft tissue defects of the anterior foot dorsal side were treated. There were 12 males and 4 females with the average age of 35 years (mean, 16-58 years). The disease causes included burn in 5 cases, traffic accident injury in 8 cases, and crush injury in 3 cases. The time from injury to admission was 2-30 hours (mean, 6.5 hours). The wound area ranged from 4 cm x 3 cm to 10 cm x 7 cm; combined injury included defects of lateral collateral ligament and joint capsule in 3 cases, and bone exposure in 12 cases, and all had exposure of tendon. Wounds were repaired with the medial sural artery perforator flap in 13 cases, and with medial sural artery perforator composite tissue flap carrying of medial head of gastrocnemius muscle flap in 3 cases. The size of flaps ranged from 5 cm x 4 cm to 11 cm x 8 cm. The donor site was sutured directly or was repaired with skin grafting. RESULTS: All flaps survived well and wounds healed with stage I; skin grafts at donor site survived and the incision healed with stage I. All patients were followed up 6-36 months (mean, 11 months). The appearance of skin flap was satisfactory, without overstaffed; the joint of reconstructed ligament was stable, without secondary deformity. There was no obvious depression at the donor site, and no effect on the function. CONCLUSION: The medial sural artery perforator flap has the advantages of relatively constant perforator anatomy, reliable blood supply, and carries the gastrocnemius muscle flap for repair of compound tissue defect. It is one of better ways to repair the anterior dorsal foot wound. PMID- 27281889 TI - [EFFECTIVENESS OF DIFFERENT FLAPS FOR REPAIR OF SEVERE PALM SCAR CONTRACTURE DEFORMITY]. AB - OBJECTIVE: To evaluate the effectiveness of different flaps for repair of severe palm scar contracture deformity. METHODS: Between February 2013 and March 2015, thirteen cases of severe palm scar contracture deformity were included in the retrospective review. There were 10 males and 3 females, aged from 14 to 54 years (mean, 39 years). The causes included burn in 9 cases, hot-crush injury in 2 cases, chemical burn in 1 case, and electric burn in 1 case. The disease duration was 6 months to 6 years (mean, 2.3 years). After excising scar, releasing contracture and interrupting adherent muscle and tendon, the soft tissues and skin defects ranged from 6.0 cm x 4.5 cm to 17.0 cm x 7.5 cm. The radial artery retrograde island flap was used in 2 cases, the pedicled abdominal flaps in 4 cases, the thoracodorsal artery perforator flap in 2 cases, the anterolateral thigh flap in 1 case, and the scapular free flap in 4 cases. The size of flap ranged from 6.0 cm x 4.5 cm to 17.0 cm x 7.5 cm. RESULTS: All flaps survived well. Venous thrombosis of the pedicled abdominal flaps occurred in 1 case, which was cured after dressing change, and healing by first intention was obtained in the others. The mean follow-up time was 8 months (range, 6-14 months). Eight cases underwent operation for 1-3 times to make the flap thinner. At last follow up, the flaps had good color, and the results of appearance and function were satisfactory. CONCLUSION: Severe palm scar contracture deformity can be effectively repaired by proper application of different flaps. PMID- 27281890 TI - [PRIMARY STUDY ON IMPLANT COVERAGE WITH LOCAL SOFT TISSUE IN IMMEDIATE IMPLANT BASED BREAST RECONSTRUCTION]. AB - OBJECTIVE: To explore the method of implant coverage with local soft tissue in immediate implant-based breast reconstruction and to evaluate the early effectiveness. METHODS: Between April 2014 and August 2015, 11 patients with breast cancer underwent immediate breast reconstruction with implants after mastectomy, and the clinical data were reviewed retrospectively. The age ranged 29-48 years (mean, 36 years). The disease duration was from 7 days to 12 months (median, 3 months). According to tumor staging, 3 cases were rated as T(is)N0M0, 4 cases as T1N0M0, and 4 cases as T2N0M0. The implants were covered with local soft tissue according to the volume of mastectomy and contralateral breast size, including pectoralis major myocutaneous flaps with inframammary adipofasical flaps (3 cases), with serratus anterior fascial flap (5 cases), with rectus sheath fascial flap (1 case), and with serratus anterior fascial flap and rectus sheath fascial flap (2 cases). The size of pectoralis major myocutaneous flaps ranged from 15 cm x 9 cm to 20 cm x 15 cm, and the serratus anterior fascial flaps from 10 cm x 8 cm to 15 cm x 10 cm, and the rectus sheath fascial flap from 8 cm x 6 cm to 10 cm x 8 cm. RESULTS: One patient had partial nipple necrosis postoperatively and was cured, and no other postoperative complications of hematoma, infection, or implant exposure was found. The patients were followed up 4-13 months (median, 8 months). The reconstructive outcomes were excellent in 10 cases and good in 1 case, with an excellent and good rate of 100%. During follow up, no rupture or exposure of the implant was observed; capsular contracture (Baker grade II) occurred in 1 case. CONCLUSION: Adequate coverage of implants with different local soft tissue flaps can achieve satisfactory early effectiveness in immediate implant-based breast reconstruction after mastectomy. PMID- 27281892 TI - Root causes must be tackled. PMID- 27281891 TI - [EFFECTIVENESS OF ROTATION-EMBEDDING TECHNOLOGY FOR TREATMENT OF MODERATE TO SEVERE INVERTED NIPPLES]. AB - OBJECTIVE: To investigate the effectiveness of rotation-embedding technology for treatment of moderate to severe inverted nipples. METHODS: Between March 2012 and March 2014, 24 patients (39 nipples) with moderate to severe inverted nipples were treated using rotation-embedding technology. The age ranged from 28 to 42 years (mean, 32 years). The bilateral nipples involved in 15 cases, unilateral nipple in 9 cases, including 30 moderate inverted nipples, 9 severe inverted nipples. The first time operation was performed in the other patients except 1 patient who had received corrective operation of bilateral nipples. RESULTS: The operation was successfully performed in all patients; primary healing of incision was obtained; no swollen, bleeding, dehiscence, or blood flow obstacle occurred. All patients were followed up 5-24 months (mean, 12 months). The shapes of nipples were satisfactory; bilateral nipples were symmetrical basically; no nipple inversion recurred, and the nipple skins had good sensation. CONCLUSION: Using rotation-embedding technology can correct moderate to severe inverted nipples effectively. PMID- 27281893 TI - Reader finds 'a bit of everything' in last month's issue. PMID- 27281894 TI - Dual responsibilities difficult. PMID- 27281895 TI - NP article strikes a chord. PMID- 27281896 TI - Butler follows protest traditions. PMID- 27281897 TI - In solidarity with Butler. PMID- 27281898 TI - Protest is good for democracy. PMID- 27281899 TI - ENs reaching their full potential. PMID- 27281900 TI - Kai Tiaki reunites old friends. PMID- 27281901 TI - Where has nursing pride gone? PMID- 27281902 TI - Venous leg ulcer study needs more participants. PMID- 27281903 TI - Violent incidents stretch ED resources. PMID- 27281904 TI - Surgery on intersex infants 'causes unnecessary trauma'. PMID- 27281905 TI - Enhancing residents' quality of life. PMID- 27281906 TI - Administering intramuscular penicillin injections to reduce rheumatic fever. PMID- 27281907 TI - Nursing in a unique part of New Zealand. PMID- 27281908 TI - Nursing on the Chathams offers rare opportunities. PMID- 27281909 TI - Disorders of the skin. PMID- 27281911 TI - Protecting patients. PMID- 27281910 TI - Improving health care for young transgender people. PMID- 27281912 TI - Caring for the patient who is deteriorating. PMID- 27281913 TI - Just a spoonful of sugar.... PMID- 27281914 TI - Gerontology: Awanui praised for gay care. PMID- 27281915 TI - HCAs' pay progression an 'obstacle course'. PMID- 27281916 TI - EFFECTS OF LONG-TIME COMMUTING AND LONG-HOUR WORKING ON LIFESTYLE AND MENTAL HEALTH AMONG SCHOOL TEACHERS IN TOKYO, JAPAN. AB - The objective of this study was to investigate the effects of long-time commuting and long-hour working on lifestyle including sleeping, physical exercise, breakfast, smoking, alcohol intake and mental health. In this cross-sectional study, data were collected from 146 school teachers in Tokyo. The binary associations of commuting time and working hours with lifestyle, mental stress measured by the General Health Questionnaire (GHQ) and stress coping measured by the Sense of Coherence (SOC) scores were examined. The Chi-square test was used for statistical analyses. Our results indicated that the mean commuting time and working hours per week of the respondents were 42.1 (SD 22.5) minutes and 50.4 (SD 8.6) hours, respectively. Longer commuting time was significantly associated with shorter working hours (p = 0.023), less physical exercise (p < 0.001) and shorter sleeping hours (p = 0.001). Longer working hours were significantly associated with more frequent working on holidays (p = 0.001), higher SOC scores (p = 0.001) and more smoking (p = 0.028). The negative association between GHQ and SOC scores was also significant (p < 0.001). Our findings revealed that long time commuters were more likely to sleep less, exercise less and work less long. Long-hour workers were more likely to commute shorter, work on holidays more frequently, smoke more and their stress coping potentials were higher. Some kinds of strategies are required to improve the healthy lifestyle for long-time com- muters or long-hour workers. Key words: stress; stress coping; general health questionnaire; sense of coherence PMID- 27281917 TI - COMPARING 3D FOOT SHAPE MODELS BETWEEN TAIWANESE AND JAPANESE FEMALES. AB - This study compares foot shape and foot dimensions between Taiwanese and Japanese females. One hundred Taiwanese and 100 Japanese female 3D foot scanning data were used for comparison. To avoid the allometry effect, data from 23 Taiwanese and 19 Japanese with foot length between 233 to 237 mm were used for shape comparison. Homologous models created for the right feet of the 42 subjects were analyzed by Multidimensional Scaling. The results showed that there were significant differences in the forefoot shape between the two groups, and Taiwanese females had slightly wider feet with straighter big toe than Japanese females. The results of body and foot dimension comparison indicated that Taiwanese females were taller, heavier and had larger feet than Japanese females, while Japanese females had significantly larger toe 1 angle. Since some Taiwanese shoemakers adopt the Japanese shoe sizing system for making shoes, appropriateness of the shoe sizing system was also discussed. The present results provide very useful information for improving shoe last design and footwear fit for Taiwanese females. PMID- 27281918 TI - SPREADSHEET-BASED PROGRAM FOR ERGONOMIC ADJUSTMENT OF NOTEBOOK COMPUTER AND WORKSTATION SETTINGS. AB - This paper discusses a computer program, ErgoNBC, which provides suggestions regarding the ergonomic settings of a notebook computer (NBC), workstation components, and selected accessories in order to help computer users to assume an appropriate work posture during the NBC work. From the users' body height, NBC and workstation component data, ErgoNBC computes the recommended tilt angle of NBC base unit, NBC screen angle, distance between the user and NBC, seat height and work surface height. If necessary, the NBC base support, seat cushion and footrest, including their settings, are recommended. An experiment involving twenty-four university students was conducted to evaluate the recommendations provided by ErgoNBC. The Rapid Upper Limb Assessment (RULA) technique was used to analyze their work postures both before and after implementing the Ergo NBC's recommendations. The results clearly showed that ErgoNBC could significantly help to improve the subjects' work postures. PMID- 27281919 TI - CONSTRUCTION AND APPLICATIONS OF A MYCORRHIZAL ARBUSCULAR SPECIFIC cDNA LIBRARY. AB - To exploit the potential benefits of mycorrhizas, we need to investigate the processes that occur in these symbiotic interactions, particularly in the arbuscular compartment where nutrients are exchanged between the plant and the fungus. Progress in this area is restricted due to the intricacy and complexity of this plant-fungus interface and many techniques that have been employed successfully in other plants and animal systems cannot be used. An effective approach to study processes in arbuscules is to examine transcript composition and dynamics. We applied laser capture microdissection (LCM) to isolate approximately 3000 arbuscules from Glomus intraradices colonised Me- dicago truncatula roots. Total RNA was extracted from microdissected arbuscules and subjected to T7 RNA polymerase-based linear amplification. Amplified RNA was then usedfor construction of a cDNA library. The presence and level of enrichment of mycorrhiza-specific transcripts was determined by quantitative Real-time and conventional PCR. To improve enrichment a cDNA library subtraction was performed. Complementation of yeast mutants deficient in the uptake of.potassium, phosphate, sulphate, amino acids, ammonium and of a Mn2+sensitive strain, demonstrates the functionality of our cDNA library. PMID- 27281920 TI - IDENTIFICATION OF QTLs ON CHROMOSOME 1B FOR GRAIN QUALITY TRAITS IN BREAD WHEAT (TRITICUM AESTIVUM L.). AB - The present study was designed considering the importance of grain quality traits, genetic diversity and marker-trait association analysis in wheat. A significant amount of genetic diversity was found for various seed traits though the genotypes included in the study were found structured. The extent of polymorphism was high with a range of 2-13 alleles and average of 6.5 alleles per locus. Population structure was detected with 30 unlinked SSRs that divided the population of 92 genotypes in three sub-populations. Extensive LD extent was found on chromosome 1B with 42 SSRs specific for 1B chromosome. Marker-trait associations were determined using mixed linear model, where, population structure and kinship calculated on the basis of unlinked markers were covariated with 1B specific markers and traits data. Eight QTLs for five traits including protein, gluten contents, test weight bread and chapati making quality. Protein content, test weight, bread quality and Glu-B1 were found significantly associated with primers WMC419 (32 cM); WMC128 (30 cM), WMC419 (32 cM); WMC818 (17 cM) and WMC416 (44 cM), respectively. PMID- 27281921 TI - THE HOMOLOGOUS IDENTIFICATION OF THE STEM RUST RESISTANCE GENES RDg5, Adf3 AND RGA1 IN THE RELATIVES OF BARLEY. AB - The barley genes Rpg5, RGA1 and Adf3, which provide a strong resistance to many pathotypes of stem rust, were cloned a few years ago, but it was still unclear whether their homologues were represented in wheat and in related species. The paper describes the results of a bioinformatic research to determine the homologues of Rpg5, RGA1 and Adf3 in the genomes of Triticum aestivum and several wild grasses, which breeders usually use as sources of stem rust resistance, and which are available in the genome databases. It was found that the Th. elongatum sequence Q9FEC6 and T. aestivum sequence Q43655 were the high identical homologues of the Adf3 sequence. T. urartu M8A999 sequence and T. aestivum W5FCU1 sequence were found to be the closest homologues of Rpg5 complete protein sequence, but the identity of their kinase domains were not as clear as that of the other domains. The separate Rpg5 kinase part analysis did not provide the strong evidences that its orthologs were presented in our corn species. T urartu M7ZZX9 sequence and T. aestivum W5FFP0 and W5F133 sequences were showed to be the homologues of RGA1. The analysis of the predicted active sites allowed finding out the difference between sequences of Rpg5, RGA1, Adf3 protein and their homologues. PMID- 27281922 TI - A HIGH FREQUENCY OF HERITABLE CHANGES IN NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER IN UKRAINE. AB - Spontaneous mutations are thought to have a stable rate for a given species. If non-adaptive, they appear at low frequencies and are governed by drift. However, environmental factors have been reported to cause spread of non-adaptive mutations in populations, governed by mechanisms, such as genetic assimilation. In the present study, we report a simultaneous appearance of a mutant and apparently non-adaptive C2 vein in Drosophila melanogaster at higher than expected frequencies in several distant populations, which excludes the role of drift or selection as the cause of the reported mutation frequencies. We discuss explanations of the phenomenon, including the role of externalfactors, such as temperature, in the possible genetic assimilation of the trait. PMID- 27281923 TI - [GENETIC VARIABILITY OF MATERNAL PLANTS AND SEED EMBRYOS OF KOCH PINE POPULATIONS (PINUS KOCHIANA KLOTZSCH EX KOCH) IN CRIMEA]. AB - Comparative studies of genetic variability were undertaken for 12 allozyme loci selections of trees and embryos of seed, and also for the crossing systems in five populations of Koch pine of (Pinus kochiana Klotzsch ex Koch) in Crimea. It was shown that in seed embryos the allelic variety peculiar to the maternal plants was restored, however the level of the available (H0) heterozygosity was considerably lower, 0.286 and 0.189 respectively. For the embryos unlike the trees, in the majority of the analyzed loci the considerable divergence was specific in the actual distribution of genotypes from the theoretically expected according to Hardy- Weinberg law. The proportion of cross pollination at the unilocal (t(s)) estimation varied from 0.384 to 0.673 in the populations, while at the multilocal ones (t(m)) it was 0.639-0.841. PMID- 27281924 TI - [INHERITANCE OF EPIDERMIS PIGMENTATION IN SUNFLOWER ACHENES]. AB - Inheritance of epidermis pigmentation in the pericarp of sunflower seeds was studied. Inheritance of pigmentation was confirmed by three alleles Ew (epidermis devoid of pigmentation), Estr (epidermal pigmentation in strips), Edg (solid pigmentation). Dominance of the lack of epidermis pigmentation over striped epidermis and striped epidermis over solid pigmentation was established. It was shown that the striped epidermis pigmentation and the presence of testa layer are controlled by two genes, expression of which is independent from each other. Yellowish hypodermis was discovered in the sample I2K2218, which is inherited monogenically dominantly. PMID- 27281925 TI - INDUCED CYTOMICTIC VARIATIONS AND SYNCYTE FORMATION DURING MICROSPOROGENESIS IN PHASEOLUS VULGARIS L. AB - The intercellular translocation of chromatin material along with other cytoplasmic contents among the proximate meiocytes lying in close contact with each other commonly referred as cytomixis was reported during microsporogenesis in Phaseolus vulgaris L., a member of the family Fabaceae. The phenomenon of cytomixis was observed at three administered doses of gamma rays viz. 100, 200, 300 Gy respectively in the diploid plants of Phaseolus vulgaris L. The gamma rays irradiated plants showed the characteristic feature of inter-meiocyte chromatin/chromosomes transmigration through various means.such as channel formation, beak formation or by direct adhesion between the PMC's (Pollen mother cells). The present study also reports the first instance of syncyte formation induced via cytomictic transmigration in Phaseolus vulgaris L. Though the frequency of syncyteformation was rather low yet these could play a significant role in plant evolution. It is speculated that syncyte enhances the ploidy level of plants by forming 2n gametes and may lead to the production ofpolyploid plants. The phenomenon of cytomixis shows a gradual inclination along with the increasing treatment doses of gamma rays. The preponderance of cytomixis was more frequent during meiosis I as compared to meiosis II. An interesting feature noticed during the present study was the channel formation among the microspores and fusion among the tetrads due to cell wall dissolution. The impact of this phenomenon is also visible on the development of post-meiotic products. The formation of heterosized pollen grains; a deviation from the normal pollen grains has also been reported. The production of gametes with unbalanced chromosomes is of utmost importance and should be given more attention in future studies as they possess the capability of inducing variations at the genomic level and can be further utilized in the improvement of germplasm. PMID- 27281926 TI - [CYTOSKELETON ORIENTATION IN THE EPIDERMAL CELLS OF ROOTS FORMED DE NOVO ON LEAF EXPLANTS UNDER CLINOROTATION]. AB - Root anatomy, cytoskeleton orientation and cell wall thickness in cells of the roots formed de novo in vitro under clinorotation (simulated microgravity) were investigated. Structure of the embryonic roots and of the roots formed de novo in cambium cells of the leaf petiole explants was shown to be similar. Root cell differentiation in vitro under clinorotation did not differ from that in control. Changes of tubulin microtubules' orientation in the epidermis of the distal elongation zone were observed under clinorotation that seems to be associated with specific physiological properties of the cells. Under clinorotation, the tendency of cell wall thinning was detected in the root cells formed in vitro. PMID- 27281927 TI - [THE ROLE OF (p)ppGpp MOLECULES IN FORMATION OF "STRICT RESPONSE" IN BACTERIA AND BIOSYNTHESIS OF ANTIBIOTICS AND MORPHOLOGICAL DIFFERENTIATION IN ACTINOMYCETES]. AB - Strict response is a pleiotropic physiological response of cells caused by lack of aminoacetylated tRNAs. Experimentally, this response occurs due to the lack of amino acids in the environment and the limitation of tRNA aminoacylation even in the presence of the corresponding amino acids in the cell. Many features of this response indicate its dependence on the accumulation of ppGpp molecules. There is a correlation between the growth rate of actinomycetes and biosynthesis of their secondary metabolites. Introduction of additional relA gene copies of ppGpp synthetase can affect the production of antibiotics in streptomycetes. The article presents the authors' own experimental data, dedicated to the influence of heterologous relA gene expression in Streptomyces nogalater cells. PMID- 27281928 TI - [Elie Metchnikoff: father of phagocytosis theory and pioneer of experiments in vivo]. PMID- 27281929 TI - [Ya.B. BLUME (on the occasion of the 60th anniversary of the birth)]. PMID- 27281930 TI - [[The Lacteol's laboratory of Dr Boucard (Laboratoire du Dr Boucard]. AB - Shortly before 1910, Dr Boucard creates his laboratory in Paris. It manufactures and sells a drug based on lactic ferments the " Lacteol du Dr Boucard" (Dr's Boucard Lacteol) that will make the fortune of the physician. The article explains Dr Boucard's life and his relationship with the arts (painting and photography), and tells the story of his laboratory until the 2000s, referring to the pharmacists who succeeded them, as well as the various buildings where were elaborated Lacteol's variants. PMID- 27281931 TI - [The pharmacopoeia of Father Morin in 1864]. AB - The "pharmacopoeia or collection of divine remedies found in the documents of an old rural priest after his death" is a publication of nearly 400 pages including a long list of diseases with their associated treatments, followed by several recipes for the day to day life (such as: how to preserve wine, how to produce Champagne's wine, recipes for filler paste, etc.). A last part, very unique, is dedicated to evil spells, i.e. to diseases that do not have natural explanations and for which Saint Benoit's medal works wonders, according to the author. This pharmacopoeia of 1864 is a typical example of "incoherent collection" mentioned by Tardieu in 1862 concerning clergy and pharmacy. It is, from that point of view, the archetype that pharmacists wanted to see disappearing after the law of germinal year XI (1803), but that persisted until the beginning of the XXth century: the illegal practice of pharmacy by priests and nuns. PMID- 27281932 TI - [Penicher: an manuscript addendum to his pharmacopoeia of 1695 on the copy of Pharmacy College Library]. AB - Penicher's pharmacopeia (1695) was part of the Library of the "College de Pharmacie". The inventory of this Library was done in 1780 and is kept by the Library of the BIU Sante, Paris-Descartes University in Paris that digitized it recently. This copy contains handwritten texts that complete the original edition. The first main addition, at the beginning of the document, is three recipes of drugs, in Latin, one of them being well known at the early 18th century, the vulnerary balm of Leonardo Fioraventi (1517-1588), that is also known as Fioraventi's alcoholate. This product will still be present in the French Codex until 1949. The Penicher' book also includes, at the end, three handwritten pages in French which represent the equipment of apothecaries. These drawings are very close to the ones of Charas' Pharmacopeia. One can think that these additions are from the second part of the 18th century, but before the gift of the pharmacopeia to the College de Pharmacie by Fourcy en 1765. The author is unknown but he is probably one of the predecessor of Fourcy in Pharmacie de l'Ours (Bear's pharmacy). This gift done by Fourcy when joining the Community of Parisians pharmacists did not prevent the fact that Fourcy was sentenced by his colleagues pharmacists, a few years later, for the sales of "Chinese specialties" that someone called Jean-Daniel Smith, a physician installed in Paris, asked him to prepare. PMID- 27281933 TI - [The complex travel of cinchona barks between Peru and Quebec Hotel-Dieu, in the middle of the eighteenth century]. AB - Duplessis sisters, who were religious nuns in Hotel-Dieu (Quebec hospital), were exchanging letters with a French apothecary from Dieppe in Normandy, named Jacques-Tranquilain Feret. They asked him to send them in Quebec the drugs and medicines their apothecary needed. Amongst these drugs were cinchona barks that came from Callao in Peru by boat, passed Cape Horn and then sailed to Cadiz, the great Spanish port. Then they embarked to Rouen, which was the French port for goods coming from overseas. The goods from Peru had then to be transported on little fishing boats to Dieppe, where Feret received the barks. The apothecary sent these drugs to Quebec by boats sailing either from Rouen or from La Rochelle. So these Peruvian drugs had to cross two times the Ocean before accessing to North America. PMID- 27281934 TI - [Treat Princes in Cordoue (9th-10th centuries)]. AB - It is proposed, through biographic notes and historical reports, to observe the physicians/power relationships in one hand, and power/medical institutions relationships on the other, in Cordoue, during omeyades' emirate and caliphate, between the 9th and 10th centuries. The gathered information allows to describe the social position of physicians who received marks of favor from princes, but also served the power in place for various responsabilities. These documents are also able to make an evaluation of the role of princes for the development of medico-pharmaceutical subjects and give indications on the health of great figures, on their diseases and the conditions of their death. PMID- 27281935 TI - [[The apothecaries of the district of Les Halles in Paris in the 17th century. Moliere's ancestors in Les Halles]. AB - Les Halles were created by King Louis VI at the begining of the 12th century as a central market for food and trade. Apothecaries conducted their trade there from that time. In the 17th century, eleven apothecaries were established in this district, bordered on the south by the rue Saint-Honore, on the east by the rue Saint-Denis, on the west by the rue de la Tonnellerie, and the north by the rue Montmartre. Their biographies have been analysed, and the data that has been collected has enabled their precise location to be fixed on a map of 1700. Moliere's ancestors, both maternal (the Cresse family) and paternal (the Pocquelin's), lived in this district. Details of their relationships with their apothecary neighbours have been revealed. PMID- 27281936 TI - [Laboratory of Pharmacognosy of Faculty of Pharmacy, University of Coimbra (Portugal): teaching and et research (1902-1980)]. AB - In this article the authors present a brief history of the Laboratory of Pharmacognosy, Faculty of Pharmacy, University of Coimbra, Portugal (1902-1980). The authors refer the importance of pharmacognosy in the study plans, the scientific research and the scientific collection of pharmacognosy, Faculty of Pharmacy, University of Coimbra. This heritage consists of collection of drugs prepared in the laboratory of pharmacognosy, a collection Drogen-Lehrsammlung purchased to E. Merck and a collection of botanic-didactic models of the XIXth century of the famous German manufacturer R. Brendel. The authors study the relationship between research and teaching, highlighting the importance of the collections of drugs. PMID- 27281937 TI - [Fragments of a correspondence between the Parisian pharmacist Emile Vial and the Dutch painter Johan-Barthold Jongkind]. AB - We study a series of exchanged original letters between the Parisian pharmacist art lover Emile Vial (1833-1917) and the Dutch painter Johan-Barthold Jongkind (1819 - 1891) from april 13th, 1876 till February 1th, 1887. PMID- 27281938 TI - [[Not Available ]]. PMID- 27281939 TI - [Multidisciplinar approach to the management of gliomas]. AB - Gliomas represent two thirds of all primary brain tumors. Their prognosis depends directly upon their level of differentiation. On MRI, tumoral aggressivity is highlighted by contrast uptake and the infiltrative nature of the lesion. Clinical suspicion must however be confirmed by histology and molecular markers become essential to refine the diagnosis and tailor the treatment. Isocytrate dehydrogenase (IDH) mutations, codeletion of 1p and 19q and the presence of methylation of the MGMT promoter identify a subgroup of gliomas with better prognosis and may help predict response to treatment. Management of patients with primary brain tumors should always be defined in multidisciplinar tumor boards involving neurosurgeons, oncologists, radiation oncologists, neuropathologists and neuroradiologists. PMID- 27281940 TI - [Immunotherapy for brain tumors: obstacles and perspectives]. AB - Glioblastomas are highly aggressive tumors. Their prognosis remain poor despite standard therapies combining surgery, radiation and temozolomide based chemotherapy. Among innovating strategies, there is a major interest for immunotherapy. During the past 3 decades, there has been a general scepticism concerning the efficacy of this approach. But the latest achievements, such as immune checkpoint inhibitors in solid tumors, and adoptive cell therapy in hematologic malignancies, have radically changed the face of the field and have already an impact on the daily practice. To which extent these advances have an impact for brain tumors also? This article aims to present the principal clinical applications of the various immune therapies currently under investigation in neurooncology and give an insight on the future perspectives in the field. PMID- 27281941 TI - [Paraneoplastic neurological syndromes: an update]. AB - Paraneoplastic neurological syndromes are a group of neurological syndromes secondary to an underlying malignancy. Associated autoantibodies can be classified according to the cellular localization of the antigen target. Onconeuronal autoantibodies (targeting intracellular antigens) strongly associate with cancer and the response to immunotherapy is often disappointing. Identifying and treating the underlying malignancy is a high priority. However, immunomodulation can provide a favourable outcome for neurological symptoms associated with autoantibodies specific for cell membrane antigens. An early recognition of these disorders following the triad "clinical neurological syndrome--specific autoantibodies--tumour research" is important so that patients can benefit from appropriate targeted treatments. PMID- 27281942 TI - [Neurological complications of anticancer treatments]. AB - After bone marrow toxicity, neurological toxicities are the second most common complications of cancer. They can be observed throughout the course of the disease or even after the end of treatment. Establishing the correct diagnosis may be a challenge but is of outmost importance to minimize the risk of long-term neurological deficits and to improve the quality of life of the patients. This review will focus on neurological complications induced by chemotherapeutic agents. As the life expectancy and number of treatment lines used in cancer patients increases, these complications are bound to become more frequent and should be aware to neurologists. PMID- 27281943 TI - [Intracranial tumors and epileptic seizures: treatment principles]. AB - Epileptic seizures represent a relatively frequent issue in patients with intracranial neoplasms, and very frequently imply the start of an antiepileptic treatment as secondary prophylaxis. Even if the current level of evidence is relatively low, compounds with a limited risk of pharmacokinetic interactions are clearly preferred. Levetiracetam is probably the most prescribed agent in this setting, while pregabalin, valproate, lacosamide and lamotrigine are valuable alternatives. The treatment choice has to consider the different profiles of side effects and should be tailored to each patient. In this setting, a multidisciplinary approach including general practicioner, oncologist and neurologist is strongly advocated. PMID- 27281944 TI - [Acute neurorehabilitation in neurooncology: Swiss Pilot Project and review of the litterature]. AB - New treatment modalities in oncology, radiation oncology and surgery have led to a significant improvement in life expectancy for cancer patients. Some will however develop severe neurologic deficits that will impact their quality of life. To limit this impact, it is essential to offer optimal neurorehabilitation. In this context, a pilot project of early and intensive neurorehabilitation for brain tumor patients has been set up. A collaboration between the teams of neurooncology, acute neurorehabilitation and neurosurgery from the CHUV and the Clinique La Ligniere allows an intensive and direct neurorehabilitation following neurosurgery. This neuroreeducation has allowed 75% of the patients included in this program to return home. PMID- 27281945 TI - [Palliative care for glioblastoma]. AB - Patients with glioblastoma have a limited life expectancy and an impaired quality of life and they should be offered palliative care soon after the diagnosis is established. Still, only a quarter of patients aged over 65 return home or medical institution after completing treatments. Home care must be promoted by coordinating assistance and care, combining disciplines such as physiotherapy and ergotherapy, medical and nursing care and psychosocial support. Patients are at risk of mood, personality and behavioural disorders. Limited awareness of these troubles and their physical limitations alter their capacity of rehabilitation and social relationships. Isolation of relatives, exhaustion and misunderstandings should be prevented. The therapeutic goals should be discussed and determined upstream to anticipate difficulties and questions concerning end of life. PMID- 27281947 TI - [Not Available]. PMID- 27281946 TI - [Not Available]. PMID- 27281948 TI - [Not Available]. PMID- 27281949 TI - [Not Available]. PMID- 27281950 TI - [Not Available]. PMID- 27281951 TI - [Not Available]. PMID- 27281952 TI - [Not Available]. PMID- 27281953 TI - [Not Available]. PMID- 27281954 TI - [Not Available]. PMID- 27281955 TI - Overview: Mechanism and Control of a Prosthetic Arm. AB - Continuous growth in industrialization and lack of awareness in safety parameters the cases of amputations are growing. The search of safer, simpler and automated prosthetic arms for managing upper limbs is expected. Continuous efforts have been made to design and develop prosthetic arms ranging from simple harness actuated to automated mechanisms with various control options. However due the cost constraints, the automated prosthetic arms are still out of the reach of needy people. Recent data have shown that there is a wide scope to develop a low cost and light weight upper limb prosthesis. This review summarizes the various designs methodologies, mechanisms and control system developed by the researchers and the advances therein. Educating the patient to develop acceptability to prosthesis and using the same for the most basic desired functions of human hand, post amputation care and to improve patient's independent life is equally important. In conclusion it can be interpreted that there is a wide scope in design in an adaptive mechanism for opening and closing of the fingers using other methods of path and position synthesis. Simple mechanisms and less parts may optimize the cost factor. Reduction in the weight of the prosthesis may be achieved using polymers used for engineering applications. Control system will remain never ending challenge for the researchers, but it is essential to maintain the simplicity from the patients perspective. PMID- 27281956 TI - Evaluation of Mechanical and Chemical Stimulations on Osteocalcin and Runx2 Expression in Mesenchymal Stem Cells. AB - The osseous tissue repair and regeneration have great importance in orthopedic and maxillofacial surgery. Tissue engineering makes it possible to cure different tissue abnormalities using autologous grafts. It is now obvious that mechanical loading has essential role in directing cells to differentiation. In this study, the influence of cyclic uniaxial loading and its combination with chemical factors on expression of osteogenic markers was investigated. Rat bone marrow derived stem cells were isolated and cultured. In one group cells were maintained in chemical induction medium. In another group cells were subjected to cyclic uniaxial strain with 3% amplitude and 0.3 Hz frequency for 24 hours and in the last group cells were affected by induction medium and physical stimulation. TaqMan Real time PCR and immunocytochemistry were done to evaluate gene expression variations. Moreover, a small incision was made to access the bone of the cranium and induced cells were seeded on collagen based scaffolds and finally the cell seeded scaffolds were implanted. Results indicated that mechanical loading alone caused a phenomenal increase in Runx2 and osteocalcin expression. Remarkable increment in gene expression was gained when induction medium were added to mechanical stimulation. The order of chemical and mechanical stimulation caused different effects and results were much better when the cells were affected by mechanical strain at first. Histological analysis showed mechanical stimulation could promote bone ingrowth in vivo. These evidences demonstrated that combination of chemical factors with mechanical strain was much more effective for directing osteogenesis since these elements have synergistic effects. PMID- 27281958 TI - An Aesthetics Focus: For Good Reason. PMID- 27281957 TI - Size-Dependent Diffusion of Dextrans in Excised Porcine Corneal Stroma. AB - Delivery of therapeutic agents to the eye requires efficient transport through cellular and extracellular barriers. We evaluated the rate of diffusive transport in excised porcine corneal stroma using fluorescently labeled dextran molecules with hydrodynamic radii ranging from 1.3 to 34 nm. Fluorescence correlation spectroscopy (FCS) was used to measure diffusion coefficients of dextran molecules in the excised porcine corneal stroma. The preferential sensitivity of FCS to diffusion along two dimensions was used to differentially probe diffusion along the directions parallel to and perpendicular to the collagen lamellae of the corneal stroma. In order to develop an understanding of how size affects diffusion in cornea, diffusion coefficients in cornea were compared to diffusion coefficients measured in a simple buffer solution. Dextran molecules diffuse more slowly in cornea as compared to buffer solution. The reduction in diffusion coefficient is modest however (67% smaller), and is uniform over the range of sizes that we measured. This indicates that, for dextrans in the 1.3 to 34 nm range, the diffusion landscape of corneal stroma can be represented as a simple liquid with a viscosity approximately 1.5 times that of water. Diffusion coefficients measured parallel vs. perpendicular to the collagen lamellae were indistinguishable. This indicates that diffusion in the corneal stroma is not highly anisotropic. Our results support the notion that the corneal stroma is highly permeable and isotropic to transport of hydrophilic molecules and particles with hydrodynamic radii up to at least 34 nm. PMID- 27281959 TI - Oral Cancer Screening. Reducing Fear Using Salivary Diagnostics. PMID- 27281960 TI - "Tommy, Can You Hear Me?". PMID- 27281961 TI - Mark T Murphy, DDS, reflects on today's new business models in dentistry. PMID- 27281962 TI - Edward Shellard, DMD, Vice President of Sales and Marketing, Carestream Dental. PMID- 27281963 TI - Danny Marinkovic, CDT, COO, Synergy 3D Dental Laboratory. PMID- 27281964 TI - Ceramic Crown for an Implant Abutment. PMID- 27281965 TI - Your Patients Can't Sleep? Have You Checked the Size of Their Tongue and Tonsils? PMID- 27281966 TI - BIOLASE Unveils New Learning Center. PMID- 27281967 TI - Are We in Good Shape? Fat Chance! PMID- 27281968 TI - University of Connecticut School of Dental Medicine Wins Gies Award. PMID- 27281969 TI - Small-Diameter Implants. PMID- 27281970 TI - Immediate Placement of SDIs in the Maxillary Arch. Immediate Post-Extraction Placement. PMID- 27281971 TI - Immediately Loading Dental Implants. Doing It Right for Long-Term Success. PMID- 27281972 TI - Inflection Points in Dental Imaging. PMID- 27281974 TI - Aesthetics and Removable Prosthetics. PMID- 27281973 TI - Putting Material Science to Work. Use of a Self Polishing Universal Nanohybrid Composite. PMID- 27281975 TI - Interdisciplinary Management of Worn Anterior Teeth. Facially Generated Treatment Planning. PMID- 27281976 TI - Service With a Smile. PMID- 27281977 TI - Vital Pulp Therapy in Primary Teeth: An Update. PMID- 27281978 TI - Platelet-Rich Growth Factor for Lip and Perioral Rejuvenation. A Case Study on "The Kiss Shot". PMID- 27281979 TI - [Heinz Kohut and Vienna]. PMID- 27281980 TI - [August Aichhorn and Heinz Kohut. Their correspondence 1946 - 1949]. PMID- 27281981 TI - [The reception of Heinz Kohut in Germany]. AB - First the discussion of Kohut's new ideas in the United States is sketched as a background. The response to these ideas was divided: on the one hand they were hailed as important innovations of psychoanalytic theory, and a circle of colleagues formed around their author; on the other hand they were violently rejected, and old friends distanced themselves from him. In Germany Kuhut's ideas were initially well received. His visits, lectures and supervisions resulted in a lively exchange and a number of friendships. When the differences between Kohutian and classical theory became evident this led increasingly to disillusionment and retreat. De-emphasizing drive and ego psychology had considerable consequences for psychoanalytic technique as well as for the analyst's Menschenbild, his relationship to the patient and his critical self reflection. In Germany, too, a circle of colleagues emerged, following and elaborating the ideas of Kohut. PMID- 27281982 TI - [The politicization of narcissism: Reading Kohut with and through Morganthaler]. AB - While in the US in the 1970s, Heinz Kohut's work served as a major rescue operation for a psychoanalytic profession that was in deep crisis, the reception in the German-speaking lands was, for multiple reasons, ultimately marked by far more ambivalence. No one explicated and defended Kohut more vigorously to his professional peers as well as to a younger generation of left-leaning psychoanalysts than the charismatic Swiss psychoanalyst (and coinventor of ethnopsychoanalysis) Fritz Morgenthaler. It was, furthermore, specifically in engaged grappling with Kohut's creative clinical innovations as well as his blind spots that Morgenthaler--as a close reading of their correspondence and respective writings shows--developed his own distinctive perspectives on the enduring riddle of how best to theorize the interrelationships between "the sexual" and other realms of existence. It was also in this context that Morgenthaler became the first European analyst of any nationality to articulate an eloquent rebuttal to the homophobic consensus that had become consolidated across the psychoanalytic diaspora since Freud's death. PMID- 27281983 TI - [From anamnesis to the art of interpretation, or: What is a "genuine" psychoanalyst? Wolfgang Warda, Ludwig Binswanger, Wilhelm Strohmayer and the origins of psychoanalysis in Thuringia]. AB - Warda and Strohmayer from Thuringia were among the first German physicians who developed an interest in Freuds theory and therapeutic method around 1900. Their contributions reflect the influence of Otto Binswanger, professor of psychiatry in Jena, a representative of the "psychological direction" in psychiatry which in the beginning was relatively receptive to Freud. The paper discusses their rapprochement to, and detachment from, the Freudian school, including also the work of a third young physician: Ludwig Binswanger, Otto's nephew, who was active in Jena at the same time. It points to certain factors contributing to the increasing rejection Freud met in academic circles which have been underrated to date: (1) the transformation of psychoanalysis into an art of interpretation; (2) the introduction of transference. Both factors which were elaborated by Freud as essentials of his theoretical and practical approach around 1900 and published in 1904/05, undermined the claim of academic medicine to objectivity. The paper describes how psychoanalysis officially abandoned the scientific standards of contemporary medicine at the Weimar congress in 1911, at the same time as Warda and Strohmayer left the Freudian group. PMID- 27281984 TI - ["The incomparable Doctor Arthur Ludwig". A biographical sketch]. AB - In two separate papers, two participants of the Weimar congress are identified on the famous congress photo for the first time. --Stephan von Minden provides a pioneering biographical sketch of the Munich neurologist A. Ludwig. Co-founder of the Munich IPA branch in 1911, and friend of the poet Else Lasker-Schuler and the educational reformer Paul Geheeb, Ludwig played a certain role in cultural history as a member of the "Munich bohemian scene" and head of a "medical family resort". --Reinhard Lampe highlights the life and work of psychiatrist E. Rehm, also a founding member of the Munich IPA branch. He directed a private sanatorium and exerted a considerable influence on medical politics in Munich for many years. An ardent National Socialist, Rehm sold his sanatorium to the Nazis in 1941. PMID- 27281985 TI - [Ernst Rehm and the Neufriedenheim sanatorium]. AB - In two separate papers, two participants of the Weimar congress are identified on the famous conigress photo for the first time. --Stephan von Minden provides a pioneering biographical sketch of the Munich neurologist A. Ludwig. Co-founder of the Munich IPA branch in 1911, and friend of the poet Else Lasker-Schuler and the educational reformer Paul Geheeb, Ludwig played a certain role in cultural history as a member of the "Munich bohemian scene" and head of a "medical family resort". --Reinhard Lampe highlights the life and work of psychiatrist E. Rehm, also a founding member of the Munich IPA branch. He directed a private sanatorium and exerted a considerable influence on medical politics in Munich for many years. An ardent National Socialist, Rehm sold his sanatorium to the Nazis in 1941. PMID- 27281986 TI - [Is Freud the author of the "aphasia" article in Villaret's Handworterbuch der Gesamten Medizin (1888)? A reply to Anneliese Menninger]. AB - In 2011/12 Menninger rejected my proposition that Freud could not have composed the "aphasia" article in Villaret's medical dictionary. In this reply I argue in favour of my initial view that Freud is not the author of the article that has been attributed to him for over 60 years. PMID- 27281987 TI - [The "aphasia" article in Villaret's Handworterbuch]. AB - Freud's authorship is founded on three arguments: 1) the reasoning of the article is close to Charcot's lectures which Freud had just translated; 2) there is a specific Freudian core thesis, common to the article and his later writings, namely the notion of an associative speech area extending between the "motor fields of the cortex and those of the optic and auditory nerves" and touching them like "corners" of a continuous field; 3) general observations on the revision or non- revision of articles taken over from the 1st to the 2nd edition of Villaret. PMID- 27281988 TI - MEMORIAL TRIBUTE To Professor Wladyslaw J.H. Kunicki-Goldfinger (1916-1995). PMID- 27281989 TI - The Functions of Effector Proteins in Yersinia Virulence. AB - Yersinia species are bacterial pathogens that can cause plague and intestinal diseases after invading into human cells through the Three Secretion System (TTSS). The effect of pathogenesis is mediated by Yersinia outer proteins (Yop) and manifested as down-regulation of the cytokine genes expression by inhibiting nuclear factor-kappa-gene binding (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways. In addition, its pathogenesis can also manipulate the disorder of host innate immune system and cell death such as apoptosis, pyroptosis, and autophagy. Among the Yersinia effector proteins, YopB and YopD assist the injection of other virulence effectors into the host cytoplasm, while YopE, YopH, YopJ, YopO, and YopT target on disrupting host cell signaling pathways in the host cytosols. Many efforts have been applied to reveal that intracellular proteins such as Rho-GTPase, and transmembrane receptors such as Toll-like receptors (TLRs) both play critical roles in Yersinia pathogenesis, establishing a connection between the pathogenic process and the signaling response. This review will mainly focus on how the effector proteins of Yersinia modulate the intrinsic signals in host cells and disturb the innate immunity of hosts through TTSS. PMID- 27281990 TI - Recovery of Gram-Positive Cocci and Candida albicans from Peroxygen/Silver-Based Disinfectants. AB - Neutralization method evaluation is an important first step in a disinfectant validation study program. It is also crucial in assessment of the efficiency of microbial recovery media in the presence of a residual biocidal agent. In the present study, four commercially available peroxygen/silver-based disinfectant formulae--intended to be used in a pharmaceutical facility sanitization program- were tested at two dilutions against three Gram-positive cocci and one yeast; Staphylococcus aureus (ATCC 6538), Kucoria rhizophila (ATCC 9341) and Candida albicans (ATCC 10231) and Staphylococcus capitis as an environmental monitoring (EM) isolate sample (identified by miniaturized biochemical identification system). Disinfectants preparation, dilutions and the test procedure were carried on in laboratory under conditions simulating the working environment of 20-25 degrees C and RH% 40-60. In-house made neutralizing broth was mixed with biocidal agents to make two dilutions of each disinfectant forming Peroxygen: neutralizing broth ratios of 1:10 and 1:100 (v/v). Three populations were established and two comparison ratio groups were examined, namely neutralizer efficacy and neutralizer toxicity. Two acceptance criteria were tested. One criterion showed higher rate of neutralization success than the other. S. aureus showed the highest rate of successful microbial recovery from neutralization process. The Disinfectant (Bixco) was exceptionally neutralized at all dilutions with all microorganisms. In conclusion, in-house made neutralizing broth effectively neutralized all disinfectants with all the tested microorganisms at 1:100 (v/v); thus, it can be used in sanitizer validation studies and EM media. PMID- 27281991 TI - Effectiveness of Antipseudomonal Antibiotics and Mechanisms of Multidrug Resistance in Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is a leading human pathogen that causes serious infections at various tissues and organs leading to life threatening health problems and possible deadly outcomes. Resistance patterns vary widely whether it is from hospitals or community acquired infections. Reporting resistance profiles to a certain antibiotics provide valuable information in a given setting, but may be extrapolated outside the sampling location. In the present study, P. aeruginosa isolates were screened to determine their susceptibilities against anti pseudomonal antimicrobial agents and possible existing mechanisms of resistance were determined. Eighty-six isolates of P. aeruginosa were recovered. Isolates representing different resistance profiles were screened for the existence of three different resistance mechanisms including drug inactivation due to metallo beta-lactamases, drug impermeability by outer membrane proteins and drug efflux. All tested isolates showed uniform susceptibility (100%, n = 86/86) to piperacillin, meropenem, amikacin, and polymyxin B. A single isolate was found to be imipenem resistant (99%, n = 85/86). The possible mechanisms of resistance of P. aeruginosa to imipenem involve active drug efflux pumps, outer membrane impermeability as well as drug inactivating enzymes. These findings demonstrate the fundamental importance of the in vitro susceptibility testing of antibiotics prior to antipseudomonal therapy and highlight the need for a continuous antimicrobial resistance surveillance programs to monitor the changing resistance patterns so that clinicians and health care officials are updated as to the most effective therapeutic agents to combat the serious outcomes of P. aeruginosa infections. PMID- 27281992 TI - Streptococcus anginosus (milleri) Group Strains Isolated in Poland (1996-2012) and their Antibiotic Resistance Patterns. AB - Streptococcus anginosus, Streptococcus intermedius and Streptococcus constellatus form a group of related streptococcal species, namely the Streptococcus Anginosus Group (SAG). The group, previously called "milleri" had been rarely described until 1980/1990 as source of infections. Nowadays SAG bacteria are often described as pathogens causing predominantly purulent infections. The number of infections is highly underestimated, as SAG strains are often classified in the microbiology laboratory as less virulent "viridans streptococci" Epidemiological situation regarding SAG infections in Poland has been unrecognized, therefore we performed a retrospective analysis of strains isolated between 1996 and 2012. Strains suspected of belonging to SAG were re-identified using an automated biochemical approach (Vitek2) and MALDI-TOF MS. We performed first analysis of antibiotic resistance among SAG strains isolated in Poland using automated methods (Vitek2), disk diffusion tests and E-Tests. We also performed PCR detection of resistance determinants in antibiotic resistant strains. Clonal structure of analyzed strains was evaluated with PFGE and MLVF methods. All three species are difficult to distinguish using automated diagnostic methods and the same is true for automated MIC evaluation. Our analysis revealed SAG strains are rarely isolated in Poland, predominantly from purulent infections. All isolates are very diverse on the genomic level as estimated by PFGE and MLVF analyses. All analyzed strains are sensitive to penicillin, a substantial group of strains is resistant to macrolides and the majority of strains are resistant to tetracycline. PMID- 27281993 TI - Comparison of Free and Immobilized L-asparaginase Synthesized by Gamma-Irradiated Penicillium cyclopium. AB - Gamma irradiation is used on Penicillium cyclopium in order to obtain mutant cells of high L-asparaginase productivity. Using gamma irradiation dose of 4 KGy, P. cyclopium cells yielded L-asparaginase with extracellular enzyme activity of 210.8 +/- 3 U/ml, and specific activity of 752.5 +/- 1.5 U/mg protein, which are 1.75 and 1.53 times, respectively, the activity of the wild strain. The enzyme was partially purified by 40-60% acetone precipitation. L-asparaginase was immobilized onto Amberlite IR-120 by ionic binding. Both free and immobilized enzymes exhibited maximum activity at pH 8 and 40 degrees C. The immobilization process improved the enzyme thermal stability significantly. The immobilized enzyme remained 100% active at temperatures up to 60 degrees C, while the free asparaginase was less tolerant to high temperatures. The immobilized enzyme was more stable at pH 9.0 for 50 min, retaining 70% of its relative activity. The maximum reaction rate (V(max)) and Michaelis-Menten constant (K(m)) of the free form were significantly changed after immobilization. The K(m) value for immobilized L-asparaginase was about 1.3 times higher than that of free enzyme. The ions K+, Ba2+ and Na+ showed stimulatory effect on enzyme activity with percentages of 110%, 109% and 106% respectively. PMID- 27281994 TI - Characterization and Optimization of Biosynthesis of Bioactive Secondary Metabolites Produced by Streptomyces sp. 8812. AB - The nutritional requirements and environmental conditions for a submerged culture of Streptomyces sp. 8812 were determined. Batch and fed-batch Streptomyces sp. 8812 fermentations were conducted to obtain high activity of secondary metabolites. In the study several factors were examined for their influence on the biosynthesis of the active metabolites-7-hydroxy-6-oxo-2,3,4,6 tetrahydroisoquinoline-3-carboxy acid (C10H9NO4) and N-acetyl-3,4-dihydroxy-L phenylalanine (C11H13NO5): changes in medium composition, pH of production medium, various growth phases of seed culture, amino acid supplementation and addition of anion exchange resin to the submerged culture. Biological activities of secondary metabolites were examined with the use of DD-carboxypeptidase 64-575 and horseradish peroxidase. Streptomyces sp. 8812 mycelium was evaluated under fluorescent microscopy and respiratory activity of the strain was analyzed. Moreover, the enzymatic profiles of the strain with the use of Api ZYM test were analyzed and genetic analysis made. Phylogenetic analysis of Streptomyces sp. 8812 revealed that its closest relative is Streptomyces capoamus JCM 4734 (98%), whereas sequence analysis for 16S rRNA gene using NCBI BLAST algorithm showed 100% homology between these two strains. Biosynthetic processes, mycelium growth and enzyme inhibitory activities of these two strains were also compared. PMID- 27281995 TI - Isolation and Characterization of alpha-Endosulfan Degrading Bacteria from the Microflora of Cockroaches. AB - Extensive applications of organochlorine pesticides like endosulfan have led to the contamination of soil and environments. Five different bacteria were isolated from cockroaches living in pesticide contaminated environments. According to morphological, physiological, biochemical properties, and total cellular fatty acid profile by Fatty Acid Methyl Esters (FAMEs), the isolates were identified as Pseudomonas aeruginosa G1, Stenotrophomonas maltophilia G2, Bacillus atrophaeus G3, Citrobacter amolonaticus G4 and Acinetobacter lwoffii G5. This is the first study on the bacterial flora of Blatta orientalis evaluated for the biodegradation of alpha-endosulfan. After 10 days of incubation, the biodegradation yields obtained from P. aeruginosa G1, S. maltophilia G2, B. atrophaeus G3, C. amolonaticus G4 and A. lwoffii G5 were 88.5% , 85.5%, 64.4%, 56.7% and 80.2%, respectively. As a result, these bacterial strains may be utilized for biodegradation of endosulfan polluted soil and environments. PMID- 27281996 TI - Bacterial Diversity and Composition in Oylat Cave (Turkey) with Combined Sanger/Pyrosequencing Approach. AB - The microbiology of caves is an important topic for better understanding subsurface biosphere diversity. The diversity and taxonomic composition of bacterial communities associated with cave walls of the Oylat Cave was studied first time by molecular cloning based on Sanger/pyrosequencing approach. Results showed an average of 1,822 operational taxonomic units per sample. Clones analyzed from Oylat Cave were found to belong to 10 common phyla within the domain Bacteria. Proteobacteria dominated the phyla, followed by Actinobacteria, Acidobacteria and Nitrospirae. Shannon diversity index was between to 3.76 and 5.35. The robust analysis conducted for this study demonstrated high bacterial diversity on cave rock wall surfaces. PMID- 27281997 TI - Biochemical and Molecular Characterization of Carotenogenic Flavobacterial Isolates from Marine Waters. AB - Carotenoids are known to possess immense nutraceutical properties and microorganisms are continuously being explored as natural source for production of carotenoids. In this study, pigmented bacteria belonging to Flavobacteriaceae family were isolated using kanamycin-containing marine agar and identified using the molecular techniques and their phenotypic characteristics were studied along with their potential to produce carotenoids. Analysis of random amplification of polymorphic DNA (RAPD) banding patterns and the fragment size of the bands indicated that the 10 isolates fall under two major groups. Based on 16S rRNA gene sequence analysis the isolates were identified as Vitellibacter sp. (3 isolates), Formosa sp. (2 isolates) and Arenibacter sp. (5 isolates). Phenotypically, the isolates showed slight variation from the reported species of these three genera of Flavobacteriaceae. Only the isolates belonging to Vitellibacter and Formosa produced flexirubin, a typical yellow orange pigment produced by most of the organisms of the family Flavobacteriaceae. Vitellibacter sp. and Formosa sp. were found to produce higher amount of carotenoids compared to Arenibacter sp. and zeaxanthin was found to be the major carotenoid produced by these two species. The study indicated that Vitellibacter sp. and Formosa sp. can be exploited for production of carotenoids, particularly zeaxanthin. PMID- 27281998 TI - Serotype-Specific Pneumococcal Status prior to PCV 13 Administration in Children and Adolescents with Inflammatory Bowel Disease. AB - The aim of this study was to evaluate the serotype-specific pneumococcal status of children and adolescents with inflammatory bowel disease (IBD) who were naive to pneumococcal vaccination before administering the 13-valent pneumococcal conjugate vaccine (PCV 13). This was an open, prospective study on children and adolescents aged 5-18 years who had IBD and were naive to pneumococcal vaccination. A single dose of PCV 13 was administered to each patient. The geometric mean concentrations (GMCs) were measured for all 13 serotypes. A total of 122 subjects completed the study. Prevaccination GMCs ranged from 0.55 MUg/ml (serotype 4) to 4.26 MUg/mI (serotype 19A). Prior to the administration of PCV 13, high GMCs were detected in older children and adolescents who had IBD and were naive to pneumococcal vaccination. PMID- 27281999 TI - Prevalence of Urogenital Mycoplasmas Among Men with NGU in Upper Silesia, Poland. Preliminary Study. AB - The prevalence of urogenital mycoplasmas in men with NGU in Upper Silesia (Poland) was studied. Mycoplasmas were detected in 36.7% men (Ureaplasma parvum and Mycoplasma genitalium were found in 30% and 16.7% respectively). Urealyticum urealyticum was not detected. We suggest including M. genitalium in the diagnostic scheme for nongonococcal urethritis (NGU). PMID- 27282000 TI - Assessment of the Microbiological Status of Probiotic Products. AB - The aim of this study was to perform the microbiological analysis of quality of 25 probiotic products, available on the Polish market. Analysis of bacterial viability in probiotic products showed that not all of these preparations possess a suitable number of bacteria. Moreover, some of the tested probiotic products contained bacterial strains other than those declared by the manufacturer. All tested strains recovered from probiotic products were found to be resistant to metronidazole and susceptible to nitrofurantoin. The susceptibility to other antibiotics was strain specific. Probiotic products should be subject to regular and thorough inspection by appropriate institutions. PMID- 27282001 TI - Antimicrobial Activity of Penicillin G and N-acetylcystein on Planktonic and Sessile Cells of Streptococcus suis. AB - The aim of this study was to investigate the capacity of Streptococcus suis strains to form biofilms and to evaluate the antimicrobial activity of Penicillin G and N-acetylcystein (NAC) on both S. suis sessile and planktonic forms. Only non-typeable isolates of S. suis were correlated with a greater biofilm formation capacity. The MCI of Penicillin G and NAC required for inhibiting biofilm growth were higher than the required concentration for inhibiting planktonic growth. The combinations of NAC and Penicillin G showed a strong synergistic activity that inhibited biofilm formation and disrupted the pre-formed biofilm of S. suis. PMID- 27282002 TI - Usefulness of CHROMagar Candida Medium, Biochemical Methods--API ID32C and VITEK 2 Compact and Two MALDI-TOF MS Systems for Candida spp. Identification. AB - This study was conducted to compare of the yeasts identification results obtained with two new systems using the MALDI-TOF MS technique with the ones obtained using the routine identification methods of Candida spp. in clinical microbiology laboratories. All 124 Candida spp. isolates were recovered from the routine examination of clinical specimens in microbiological laboratories and collected in the Centre of Quality Control in Microbiology in Warsaw (Poland). Our findings confirm the high agreement (98%) of fungal identification using the standard, biochemistry laboratory methods and mass spectrometry technique. PMID- 27282003 TI - Enterobacter asburiae KUNi5, a Nickel Resistant Bacterium for Possible Bioremediation of Nickel Contaminated Sites. AB - Nickel resistant bacterial strain Enterobacter asburiae KUNi5 was isolated and showed resistance up to 15 mM and could remove Ni optimally better at 37 degrees C and pH 7. Maximum removal was found at initial concentration of 0.5 to 2 mM, however, growth and Ni removal were affected by other heavy metals. Major amount of the metal was accumulated in the membrane fractions and certain negatively charged groups were found responsible for Ni binding. KUNi5 could also produce 1 aminocyclopropane-1-carboxylate deaminase, indole-acetic acid and siderophore. It seems that KUNi5 could be a possible candidate for Ni detoxification and plant growth promotion in Ni-contaminated field. PMID- 27282004 TI - IgG Avidity: an Important Serologic Marker for the Diagnosis of Tick-Borne Encephalitis Virus Infection. AB - A total of 52 serum samples from patients with symptoms suggestive of tick-borne encephalitis virus (TBEV) infection and positive IgM and/or IgG antibodies were tested for IgG avidity. Acute/recent TBEV infection was confirmed by low/borderline avidity index (AI) in 94.8% IgM positive/IgG positive samples, while in 5.2% high AI was found indicating persisting IgM antibodies. Majority of IgM negative/IgG positive samples (78.6%) showed high AI consistent with past TBEV infection. However, in 21.3% patients without measurable IgM antibodies current/recent infection was confirmed by AI. IgG avidity represents an additional serologic marker that improves diagnosis of TBEV, especially in cases of atypical antibody response. PMID- 27282006 TI - Acute Emergencies in Adolescents. PMID- 27282005 TI - Etiologic Agents and Antifungal Susceptibility of Oral Candidosis from Romanian patients with HIV-infection or type 1 diabetes mellitus. AB - This is the first Romanian investigation of oral candidosis in patients suffering of HIV-infection or type 1 diabetes mellitus (T1DM). Candida albicans was the dominant species in both types of isolates: n = 14 (46.7%) in T1DM, n = 60 (69.8%) in HIV. The most frequent non-albicans Candida spp. were Candida kefyr (n = 6; 20%) in T1DM and Candida dubliniensis (n = 8; 9.3%) in HIV. Resistance to fluconazole was detected only in the HIV non-albicans Candida group (n = 8; 9.3%). All isolates were susceptible to VOR. The experimental drug MXP had MIC values equal or close to the ones of VOR. Echinocandin resistance was more frequent than azole resistance. PMID- 27282007 TI - Adolescent Gynecologic Emergencies. AB - Adolescent females frequently present to the ED with complaints that may be caused by a gynecologic emergency. Differentiating and excluding some of the common and most serious gynecologic emergencies reviewed in this article are critical. Timely and effective treatment of these conditions, once diagnosed, can result in better health outcomes. PMID- 27282008 TI - Adolescent Male Genitourinary Emergencies. PMID- 27282009 TI - Sports-Related Head Injuries in Adolescents: A Comprehensive Update. PMID- 27282010 TI - Sports-Related Sudden Cardiac Injury or Death. AB - Symptoms such as syncope and chest pain, especially if they are accompanied by palpitations or occur with exercise in any combination, require cardiac evaluation before adolescent athletes are allowed to return to the sports field. Some life-threatening conditions will likely be associated with a family history of HCM or LQTS, but the family history may not be discovered at the first medical visit. A family history of CPVT, for example, is hard to elicit unless this diagnosis has already been established in an affected family member. The keys will be the timing of symptoms and the documentation of arrhythmia with exercise. The ECG at baseline in CPVT may be deceptively normal. Hypertrophic cardiomyopathy is progressive, so evaluation during early childhood may be negative. Long QT syndrome may not always result in an abnormal ECG, even in genetically positive individuals. A high index of suspicion is needed to make these diagnoses, especially if the family history is not available. PMID- 27282011 TI - Approach to the Adolescent with Chest Pain. PMID- 27282012 TI - Approach to the Adolescent Psychiatric and Behavioral Health Emergency. PMID- 27282013 TI - Generation Z: Adolescent Xenobiotic Abuse in the 21st Century. AB - NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support. PMID- 27282014 TI - Emergency Care of Youth with Social and Environmental Vulnerabilities. PMID- 27282015 TI - Human Immunodeficiency Virus: Adolescent Emergencies. AB - Many adolescents are at high risk for HIV infection, and those who are infected or at-risk commonly present to the ED, often as their only or frequent source of care. It is important to consider routine screening and to have a high index of suspicion for AHI in this setting. If a diagnosis of HIV infection is made, immediate linkage to care with a specialist in adolescent and young adult HIV infection should be prioritized. For the known HIV-infected patient, management must consider unique possibilities of OIs, IRIS, and medication side effects. For any patient on ART, drug-drug interactions must be noted as part of any treatment plan. If a young person presents with a recent sexual or needlestick exposure of concern, every effort to prescribe and ensure follow-up for PEP should be made. It is essential for physicians to understand and comply with local regulations regarding HIV testing and adolescents' rights for associated confidential care. Finally, physicians who see adolescents in acute care settings have a tremendous opportunity to make a difference in ensuring improved health outcomes for youth living with HIV and to prevent new infections. PMID- 27282016 TI - Evaluation and Treatment of the Adolescent Sexual Assault Patient. PMID- 27282017 TI - Update on Meningitis in Adolescents and Young Adults. PMID- 27282018 TI - Adolescent Dating Violence in the Emergency Department: Presentation, Screening, and Interventions. PMID- 27282019 TI - Syncope in Children and Adolescents. PMID- 27282020 TI - Dumbbell Defects in FeSe Films: A Scanning Tunneling Microscopy and First Principles Investigation. AB - The properties of iron-based superconductors (Fe-SCs) can be varied dramatically with the introduction of dopants and atomic defects. As a pressing example, FeSe, parent phase of the highest-Tc Fe-SC, exhibits prevalent defects with atomic scale "dumbbell" signatures as imaged by scanning tunneling microscopy (STM). These defects spoil superconductivity when their concentration exceeds 2.5%. Resolving their chemical identity is a prerequisite to applications such as nanoscale patterning of superconducting/nonsuperconducting regions in FeSe as well as fundamental questions such as the mechanism of superconductivity and the path by which the defects destroy it. We use STM and density functional theory to characterize and identify the dumbbell defects. In contrast to previous speculations about Se adsorbates or substitutions, we find that an Fe-site vacancy is the most energetically favorable defect in Se-rich conditions and reproduces our observed STM signature. Our calculations shed light more generally on the nature of Se capping, the removal of Fe vacancies via annealing, and their ordering into a ?5 * ?5 superstructure in FeSe and related alkali-doped compounds. PMID- 27282021 TI - Predictors of response to serotonin reuptake inhibitors in obsessive-compulsive disorder. AB - INTRODUCTION: 40-60% of patients with obsessive compulsive disorder (OCD) do not respond adequately to serotonin reuptake inhibitors (SRIs). It is important to identify predictors of response to help individualize treatment and identify refractory patients early in the course of treatment. AREAS COVERED: We review the current literature on predictors of response to SRIs in adult patients with OCD including clinical features, neuropsychological profile, neuroimaging, genetics and other biological factors. We conducted a literature search in PUBMED database using the MeSH terms 'Obsessive-Compulsive Disorder', 'drug therapy', 'treatment outcome', 'neuroimaging', 'genetics' 'cytokines' and obtained 60 articles. Expert commentary: Poor-insight into obsessions, symmetry/hoarding and contamination/washing dimension and the presence of certain personality disorders are associated with poor response to SRIs. Orbitofrontal cortex, anterior cingulate cortex, caudate, putamen and thalamus volume changes in structural imaging studies and altered activity in the same regions in functional imaging studies were found predictive of poor response. However, there is inconsistency with regards to direction of change. Genes involving serotonergic and glutamatergic signalling pathways have emerged as predictors in recent studies. Studies with large sample size, standardised methodology and rigorous statistical analyses are required before predictors can be utilised in routine clinical practice. PMID- 27282022 TI - The "Mendelian Gene" and the "Molecular Gene": Two Relevant Concepts of Genetic Units. AB - We focus here on two prevalent meanings of the word gene in research articles. On one hand, the gene, named here "molecular gene," is a stretch of DNA that is transcribed and codes for an RNA or a polypeptide with a known or presumed function (as in "gene network"), whose exact spatial delimitation on the chromosome remains a matter of debate, especially in cases with alternative splicing, antisense transcripts, etc. On the other hand, the gene, called here "Mendelian gene," is a segregating genetic unit which is detected through phenotypic differences associated with different alleles at the same locus (as in "gene flow"). We show that the "Mendelian gene" concept is still extensively used today in biology research and is sometimes confused with the "molecular gene." We try here to clarify the distinction between both concepts. Efforts to delineate the beginning and the end of the DNA sequence corresponding to the "Mendelian gene" and the "molecular gene" reveal that both entities do not always match. We argue that both concepts are part of two relevant frameworks for explaining the biological world. PMID- 27282024 TI - To Have and to Hold: Selection for Seed and Fruit Retention During Crop Domestication. AB - Crop domestication provides a useful model system to characterize the molecular and developmental bases of morphological variation in plants. Among the most universal changes resulting from selection during crop domestication is the loss of seed and fruit dispersal mechanisms, which greatly facilitates harvesting efficiency. In this review, we consider the molecular genetic and developmental bases of the loss of seed shattering and fruit dispersal in six major crop plant families, three of which are primarily associated with seed crops (Poaceae, Brassicaceae, Fabaceae) and three of which are associated with fleshy-fruited crops (Solanaceae, Rosaceae, Rutaceae). We find that the developmental basis of the loss of seed/fruit dispersal is conserved in a number of independently domesticated crops, indicating the widespread occurrence of developmentally convergent evolution in response to human selection. With regard to the molecular genetic approaches used to characterize the basis of this trait, traditional biparental quantitative trait loci mapping remains the most commonly used strategy; however, recent advances in next-generation sequencing technologies are now providing new avenues to map and characterize loss of shattering/dispersal alleles. We anticipate that continued application of these approaches, together with candidate gene analyses informed by known shattering candidate genes from other crops, will lead to a rapid expansion of our understanding of this critical domestication trait. PMID- 27282023 TI - The Genetic Basis of Pigmentation Differences Within and Between Drosophila Species. AB - In Drosophila, as well as in many other plants and animals, pigmentation is highly variable both within and between species. This variability, combined with powerful genetic and transgenic tools as well as knowledge of how pigment patterns are formed biochemically and developmentally, has made Drosophila pigmentation a premier system for investigating the genetic and molecular mechanisms responsible for phenotypic evolution. In this chapter, we review and synthesize findings from a rapidly growing body of case studies examining the genetic basis of pigmentation differences in the abdomen, thorax, wings, and pupal cases within and between Drosophila species. A core set of genes, including genes required for pigment synthesis (eg, yellow, ebony, tan, Dat) as well as developmental regulators of these genes (eg, bab1, bab2, omb, Dll, and wg), emerge as the primary sources of this variation, with most genes having been shown to contribute to pigmentation differences both within and between species. In cases where specific genetic changes contributing to pigmentation divergence were identified in these genes, the changes were always located in noncoding sequences and affected cis-regulatory activity. We conclude this chapter by discussing these and other lessons learned from evolutionary genetic studies of Drosophila pigmentation and identify topics we think should be the focus of future work with this model system. PMID- 27282025 TI - The Genetics Underlying Natural Variation in the Biotic Interactions of Arabidopsis thaliana: The Challenges of Linking Evolutionary Genetics and Community Ecology. AB - In the context of global change, predicting the responses of plant communities in an ever-changing biotic environment calls for a multipronged approach at the interface of evolutionary genetics and community ecology. However, our understanding of the genetic basis of natural variation involved in mediating biotic interactions, and associated adaptive dynamics of focal plants in their natural communities, is still in its infancy. Here, we review the genetic and molecular bases of natural variation in the response to biotic interactions (viruses, bacteria, fungi, oomycetes, herbivores, and plants) in the model plant Arabidopsis thaliana as well as the adaptive value of these bases. Among the 60 identified genes are a number that encode nucleotide-binding site leucine-rich repeat (NBS-LRR)-type proteins, consistent with early examples of plant defense genes. However, recent studies have revealed an extensive diversity in the molecular mechanisms of defense. Many types of genetic variants associate with phenotypic variation in biotic interactions, even among the genes of large effect that tend to be identified. In general, we found that (i) balancing selection rather than directional selection explains the observed patterns of genetic diversity within A. thaliana and (ii) the cost/benefit tradeoffs of adaptive alleles can be strongly dependent on both genomic and environmental contexts. Finally, because A. thaliana rarely interacts with only one biotic partner in nature, we highlight the benefit of exploring diffuse biotic interactions rather than tightly associated host-enemy pairs. This challenge would help to improve our understanding of coevolutionary quantitative genetics within the context of realistic community complexity. PMID- 27282026 TI - Behavioral Genetic Toolkits: Toward the Evolutionary Origins of Complex Phenotypes. AB - The discovery of toolkit genes, which are highly conserved genes that consistently regulate the development of similar morphological phenotypes across diverse species, is one of the most well-known observations in the field of evolutionary developmental biology. Surprisingly, this phenomenon is also relevant for a wide array of behavioral phenotypes, despite the fact that these phenotypes are highly complex and regulated by many genes operating in diverse tissues. In this chapter, we review the use of the toolkit concept in the context of behavior, noting the challenges of comparing behaviors and genes across diverse species, but emphasizing the successes in identifying genetic toolkits for behavior; these successes are largely attributable to the creative research approaches fueled by advances in behavioral genomics. We have two general goals: (1) to acknowledge the groundbreaking progress in this field, which offers new approaches to the difficult but exciting challenge of understanding the evolutionary genetic basis of behaviors, some of the most complex phenotypes known, and (2) to provide a theoretical framework that encompasses the scope of behavioral genetic toolkit studies in order to clearly articulate the research questions relevant to the toolkit concept. We emphasize areas for growth and highlight the emerging approaches that are being used to drive the field forward. Behavioral genetic toolkit research has elevated the use of integrative and comparative approaches in the study of behavior, with potentially broad implications for evolutionary biologists and behavioral ecologists alike. PMID- 27282027 TI - Identifying Coopted Networks and Causative Mutations in the Origin of Novel Complex Traits. AB - One of the central goals of the field of evo-devo is to understand how novel complex traits originate. Novel complex traits are often old, and this makes understanding the genetic basis of their origin difficult. The traditional genetics approach for identifying the causative mutations for trait origin, of crossing species with and without the trait, is often impossible when the species are too distantly related. Alternatively, if the species are closely related, the genetic basis of their differences is often the recent loss, rather than the gain, of the trait in one of them, and mutations resulting in trait loss are not always equivalent to those that led to trait gain. Here, we reexamine an evo-devo study of the origin of melanic spots in the wings of flies, which is presented in more than one mainstream undergraduate textbook on Evolution, as an example of molecular evolution leading to the origin of a novel trait. We put forth an alternative to the previously proposed scenario and, in our view, a more likely evolutionary framework that explains the data, the CRE-DDC model, and then review other case studies and avenues of research that should help identify where new complex traits come from, as well as the actual causative mutations underlying their origin. PMID- 27282028 TI - Looking Beyond the Genes: The Interplay Between Signaling Pathways and Mechanics in the Shaping and Diversification of Epithelial Tissues. AB - The core of Evo-Devo lies in the intuition that the way tissues grow during embryonic development, the way they sustain their structure and function throughout lifetime, and the way they evolve are closely linked. Epithelial tissues are ubiquitous in metazoans, covering the gut and internal branched organs, as well as the skin and its derivatives (ie, teeth). Here, we discuss in vitro, in vivo, and in silico studies on epithelial tissues to illustrate the conserved, dynamical, and complex aspects of their development. We then explore the implications of the dynamical and nonlinear nature of development on the evolution of their size and shape at the phenotypic and genetic levels. In rare cases, when the interplay between signaling and mechanics is well understood at the cell level, it is becoming clear that the structure of development leads to covariation of characters, an integration which in turn provides some predictable structure to evolutionary changes. We suggest that such nonlinear systems are prone to genetic drift, cryptic genetic variation, and context-dependent mutational effects. We argue that experimental and theoretical studies at the cell level are critical to our understanding of the phenotypic and genetic evolution of epithelial tissues, including carcinomas. PMID- 27282029 TI - Phenotypic Evolution With and Beyond Genome Evolution. AB - DNA does not make phenotypes on its own. In this volume entitled "Genes and Phenotypic Evolution," the present review draws the attention on the process of phenotype construction-including development of multicellular organisms-and the multiple interactions and feedbacks between DNA, organism, and environment at various levels and timescales in the evolutionary process. First, during the construction of an individual's phenotype, DNA is recruited as a template for building blocks within the cellular context and may in addition be involved in dynamical feedback loops that depend on the environmental and organismal context. Second, in the production of phenotypic variation among individuals, stochastic, environmental, genetic, and parental sources of variation act jointly. While in controlled laboratory settings, various genetic and environmental factors can be tested one at a time or in various combinations, they cannot be separated in natural populations because the environment is not controlled and the genotype can rarely be replicated. Third, along generations, genotype and environment each have specific properties concerning the origin of their variation, the hereditary transmission of this variation, and the evolutionary feedbacks. Natural selection acts as a feedback from phenotype and environment to genotype. This review integrates recent results and concrete examples that illustrate these three points. Although some themes are shared with recent calls and claims to a new conceptual framework in evolutionary biology, the viewpoint presented here only means to add flesh to the standard evolutionary synthesis. PMID- 27282031 TI - Preface. PMID- 27282030 TI - Human Phenotypic Diversity: An Evolutionary Perspective. AB - As humans migrated across the world, they encountered new environments requiring them to adapt to new challenges that presented themselves. The distribution of human phenotypes observed today is the result of this continuous adaptation, via biological/physiological and cultural means, and also by the modification of cultural practices, which leads to biological changes. In this chapter, we examine a number of adaptive traits and the roles played by their genetic and environmental determinants. We have selected a few traits used for human identification purposes (externally visible characteristics), associated with human metabolism and linked to a shift in subsistence method and food consumption. We discuss the evolutionary processes that have affected the temporal and spatial distribution of these traits, including natural, sexual, and cultural selection. PMID- 27282032 TI - Human Biology of the Amazon. PMID- 27282074 TI - High wholegrain barley beta-glucan lowers food intake but does not alter small intestinal macronutrient digestibility in ileorectostomised rats. AB - Using barley cultivars differing widely in beta-glucan content, we aimed to determine their effects on small intestinal macronutrient digestion in 24 ileorectostomised rats. The rats were fed 1 of 4 experimental diets, each containing a different barley variety, for 11 d. The diets had a content of 0, 2.1, 2.6 and 4.3 g of beta-glucan/100 g. Feed intake and faecal excretion of fat, protein, starch, and non-starch polysaccharides were determined in the final 5 d of the study and apparent macronutrient digestibility calculated. Higher dietary levels of beta-glucan (2.6% and 4.3%) lowered feed intake (by 15 and 19%, respectively) but final body weight was only lowered by the 4.3% beta-glucan diet relative to rats fed the 0% beta-glucan diet (all ps < 0.05). Protein, lipid and starch digestibility was unrelated to the dietary beta-glucan content. Higher dietary levels of barley beta-glucan lower feed intake of ileorectostomised rats, which is independent of intestinal fermentation and unrelated to macronutrient digestibility. PMID- 27282076 TI - Bibliometric analysis of scientific literature on intestinal parasites in Argentina during the period 1985-2014. AB - The study of scientific production is a good indicator of the progress in research and knowledge generation. Bibliometrics is a scientific discipline that uses a set of indicators to quantitatively express the bibliographic characteristics of scientific publications. The scientific literature on the epidemiology of intestinal parasites in Argentina is scattered in numerous sources, hindering access and visibility to the scientific community. Our purpose was to perform a quantitative, bibliometric study of the scientific literature on intestinal parasites in humans in Argentina published in the period 1985-2014. This bibliometric analysis showed an increase in the number of articles on intestinal parasites in humans in Argentina published over the past 30 years. Those articles showed a collaboration index similar to that of the literature, with a high index of institutionality for national institutions and a very low one for international collaboration. The original articles were published in scientific journals in the American Continent, Europe and Asia. The use of bibliometric indicators can provide a solid tool for the diagnosis and survey of the research on epidemiology of intestinal parasites and contributes to the dissemination and visibility of information on the scientific production developed in Argentina. PMID- 27282077 TI - Cognitive Orientation to daily Occupational Performance (CO-OP): A New Approach for Children with Cerebral Palsy. AB - AIMS: The results of a small single-case study series suggested that Cognitive Orientation to daily Occupational Performance (CO-OP) may be a successful approach for children with cerebral palsy (CP). Therefore a pilot randomized controlled trial was conducted with the following research questions-is CO-OP a feasible approach to use with children with CP, what are the effects of CO-OP when compared to usual practice, and is a larger study warranted? METHODS: 18 children between age 7 and 12 (nine in CO-OP group and nine in Current Usual Practice Approach (CUPA) group) received ten 1-hour sessions of intervention on average once per week at home. Primary outcome measures were the Canadian Occupational Performance Measure and the Performance Quality Rating Scale (PQRS). PQRS assessors were blind to group allocation and timing of assessment. RESULTS: All children in the CO-OP group were able to learn the strategies and achieve their chosen goals, thus demonstrating the feasibility of the approach. Both approaches equally promoted skill acquisition and skill maintenance at follow-up. Effect sizes suggest that CO-OP may show some advantage for transfer and maintenance. CONCLUSION: Based on these initial findings, further research is warranted. PMID- 27282075 TI - RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4. AB - BACKGROUND: Pancreatic adenocarcinoma patients have low survival rates due to late-stage diagnosis and high rates of cancer recurrence even after surgical resection. It is important to understand the molecular characteristics associated with survival differences in pancreatic adenocarcinoma tumors that may inform patient care. RESULTS: RNA sequencing was performed for 51 patient tumor tissues extracted from patients undergoing surgical resection, and expression was associated with overall survival time from diagnosis. Our analysis uncovered 323 transcripts whose expression correlates with survival time in our pancreatic patient cohort. This genomic signature was validated in an independent RNA-seq dataset of 68 additional patients from the International Cancer Genome Consortium. We demonstrate that this transcriptional profile is largely independent of markers of cellular division and present a 19-transcript predictive model built from a subset of the 323 transcripts that can distinguish patients with differing survival times across both the training and validation patient cohorts. We present evidence that a subset of the survival-associated transcripts is associated with resistance to gemcitabine treatment in vitro, and reveal that reduced expression of one of the survival-associated transcripts, Angiopoietin-like 4, impairs growth of a gemcitabine-resistant pancreatic cancer cell line. CONCLUSIONS: Gene expression patterns in pancreatic adenocarcinoma tumors can distinguish patients with differing survival outcomes after undergoing surgical resection, and the survival difference could be associated with the intrinsic gemcitabine sensitivity of primary patient tumors. Thus, these transcriptional differences may impact patient care by distinguishing patients who would benefit from a non-gemcitabine based therapy. PMID- 27282078 TI - Comparative value of blood and skin samples for diagnosis of spotted fever group rickettsial infection in model animals. AB - The definitive diagnosis of spotted fever group (SFG) rickettsioses in humans is challenging due to the retrospective nature and cross reactivity of the serological methods and the absence of reliable and consistent samples for molecular diagnostics. Existing data indicate the transient character of bacteremia in experimentally infected animals. The ability of arthropod vectors to acquire rickettsial infection from the laboratory animals in the absence of systemic infection and known tropism of rickettsial agents to endothelial cells of peripheral blood vessels underline the importance of local infection and consequently the diagnostic potential of skin samples. In order to evaluate the diagnostic sensitivity of rickettsial DNA detection in blood and skin samples, we compared results of PCR testing in parallel samples collected from model laboratory animals infected with Rickettsia rickettsii, Rickettsia parkeri and Rickettsia slovaca-like agent at different time points after infection. Skin samples were collected from ears - away from the site of tick placement and without eschars. Overall, testing of skin samples resulted in a higher proportion of positive results than testing of blood samples. Presented data from model animals demonstrates that testing of skin samples from sites of rickettsial proliferation can provide definitive molecular diagnosis of up to 60-70% of tick borne SFG rickettsial infections during the acute stage of illness. Detection of pathogen DNA in cutaneous samples is a valuable alternative to blood-PCR at least in model animals. PMID- 27282079 TI - How to Avoid Stereotypes? Evaluation of a Strategy based on Self-Regulatory Processes. AB - Based on research on the motivational processes involved in preventing and controlling stereotypes, we aimed to assess whether temporary activation of egalitarian goals - by means of a task that gives respondents exposure to a text on gender inequality - can prevent stereotyped answers on the task. The task asks participants to place women and men into a hierarchical organizational structure. Two specific objectives were established: first, to control the effect of prejudice and egalitarian commitment on the dependent variable; and second, to study gender differences in task responses. The study included 474 college students, 153 men and 321 women. Their mean age was 20.04 (SD = 4.43). ANCOVA indicated main effects of condition, F(1) = 4.15, p = .042, eta2 = .081 (control condition without goal activation vs. experimental condition with goal activation) and sex, F(1) = 40.46, p < .001, eta2 = .081, on the dependent variable (female candidates placed in the chart). Specifically, responses from participants in the experimental condition avoided stereotyped answers more than participants in the control condition. Furthermore, women's performance on the task was more egalitarian than men's. Finally, there was a significant interaction effect of condition and type of organization, F(2) = 3.97, p = .019, eta2 = .017; participants assigning candidates to the feminized organization differed the most across conditions. PMID- 27282081 TI - "Exploding" electronic cigarette: a case report. PMID- 27282080 TI - Osteogenic potential of murine periosteum for critical-size cranial defects. AB - Tissue engineering of bone has combined bespoke scaffolds and osteoinductive factors to maintain functional osteoprogenitor cells, and the periosteum has been confirmed as a satisfactory source of osteoblasts. Suitable matrices have been identified that support cell proliferation and differentiation, including demineralised bone matrix (both compatible and osteoinductive) and acellular human dermis. We have evaluated the osteogenic potential of an osteogenic unit, developed by combining periosteum, demineralised bone matrix, and acellular human dermis, in rodents with critical-size cranial defects. Briefly, remnants from the superior maxillary periosteum were used to harvest cells, which were characterised by flow cytometry and reverse retrotranscriptase-polymerase chain reaction (RT-PCR). Cells were cultured into the osteogenic unit and assessed for viability before being implanted into 3 rodents, These were compared with the control group (n=3) after three months. Histological analyses were made after staining with haematoxylin and eosin and Von Kossa, and immunostaining, and confirmed viable cells that stained for CD90, CD73, CD166, runt-related transcription factor, osteopontin, and collagen type I in the experimental group, while in the control group there was only connective tissue on the edges of the bone in the injury zone. We conclude that osteogenic unit constructs have the osteogenic and regenerative potential for use in engineering bone tissue. PMID- 27282082 TI - Mandibular fractures - towards a national standard for "time to theatre" - national audit by the BAOMS Trauma Specialist Interest Group. AB - Recent studies have shown that in most patients, a delay of several days in the treatment of mandibular fractures is not associated with adverse outcomes, and this has challenged the traditional practice of recommending treatment within 24hours. Longer hospital stays cost more and lower the patients' quality of life, but we know of no standard recommendation about when these patients should be treated. Our aim therefore was to find out how many patients had reduction and fixation of a fractured mandible by the end of the next working day, with a view to developing a national standard. We invited all oral and maxillofacial surgery (OMFS) units in the UK to participate in a prospective audit over two months, and 35 agreed. Overall, 506 patients (80%) were operated on by the end of the next working day. The time to theatre varied from 1 hour 15minutes to 11 days, 20hours and 51minutes (median 22hours 7minutes). Patients admitted to units with an OMFS trauma list were more likely to be operated on by the next working day (p=0.011) as were those operated on at the weekend (p=0.019). We think that early fixation, return of function, and discharge, benefit patients most in terms of quality of life. Also, shorter hospital stays and reduced costs increase the availability of resources for elective operations. Setting a standard will improve our service and the care we deliver. PMID- 27282083 TI - Search for a reliable model for bisphosphonate-related osteonecrosis of the jaw: establishment of a model in pigs and description of its histomorphometric characteristics. AB - The pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains unknown, and the development of a reliable experimental model would help to improve our understanding of it. We used 12 domestic pigs of which 6 made up the experimental group and were treated with zoledronate 4mg intravenously weekly for 5 weeks, while the control group (n=6) were given no drugs. On day 60 the right second maxillary and mandibular third molars were extracted. Thirty days later 3 animals in each group were killed; the rest were killed 90 days later. Histopathological specimens from the extraction sites were analysed for bone density, collagen architecture, density of osteons, and the amount of non mineralised bone. Bone density, amount of non-mineralised bone, and density of osteons differed significantly between the 2 groups (p<0.001 in each case), but the chromatic pattern dictated by the collagen architecture did not. Our results correspond to the observations that have been made in patients with BRONJ, which means that the histomorphometric conditions seen in patients can be reproduced in this experimental setting. PMID- 27282084 TI - Short-term immobilization influences use-dependent cortical plasticity and fine motor performance. AB - Short-term immobilization that reduces muscle use for 8-10h is known to influence cortical excitability and motor performance. However, the mechanisms through which this is achieved, and whether these changes can be used to modify cortical plasticity and motor skill learning, are not known. The purpose of this study was to investigate the influence of short-term immobilization on use-dependent cortical plasticity, motor learning and retention. Twenty-one adults were divided into control and immobilized groups, both of which underwent two experimental sessions on consecutive days. Within each session, transcranial magnetic stimulation (TMS) was used to assess motor-evoked potential (MEP) amplitudes, short- (SICI) and long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF) before and after a grooved pegboard task. Prior to the second training session, the immobilized group underwent 8h of left hand immobilization targeting the index finger, while control subjects were allowed normal limb use. Immobilization produced a reduction in MEP amplitudes, but no change in SICI, LICI or ICF. While motor performance improved for both groups in each session, the level of performance was greater 24-h later in control, but not immobilized subjects. Furthermore, training-related MEP facilitation was greater after, compared with before, immobilization. These results indicate that immobilization can modulate use-dependent plasticity and the retention of motor skills. They also suggest that changes in intracortical excitability are unlikely to contribute to the immobilization-induced modification of cortical excitability. PMID- 27282086 TI - Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain. AB - Polysialated neural cell adhesion molecule (PSA-NCAM) is a membrane bound glycoprotein widely expressed during nervous system development. While commonly described in the neurogenic niches of the adult human brain, there is limited evidence of its distribution in other brain regions. PSA-NCAM is an important regulator of cell-cell interactions and facilitates cell migration and plasticity. Recent evidence suggests these functions may be altered in neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). This study provides a detailed description of the PSA-NCAM distribution throughout the human brain and quantitatively compares the staining load in cortical regions and sub-cortical structures between the control, AD and PD brain. Our results provide evidence of widespread, yet specific, PSA-NCAM expression throughout the human brain including regions devoid of PSA-NCAM in the rodent brain such as the caudate nucleus (CN) and cerebellum (CB). We also detected a significant reduction in PSA-NCAM load in the entorhinal cortex (EC) of cases that was inversely correlated with hyperphosphorylated tau load. These results demonstrate that PSA-NCAM-mediated structural plasticity may not be limited to neurogenic niches and is conserved in the aged brain. We also provide evidence that PSA-NCAM is reduced in the EC, a region severely affected by AD pathology. PMID- 27282087 TI - Reduced response to chronic mild stress in PACAP mutant mice is associated with blunted FosB expression in limbic forebrain and brainstem centers. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) has been implicated in stress adaptation with potential relevance in mood disorder management. PACAP deficient (KO) mice on CD1 background were shown to have depression-like phenotype. Here we aimed at investigating effects of chronic variable mild stress (CVMS) in non-injected, vehicle and imipramine-treated KO mice vs. wildtype (WT) counterparts. We hypothesized reduced FosB neuronal activity in stress-related centers, altered activity and peptide/neurotransmitter content of corticotropin releasing factor (CRF) cells of the oval (ovBST) bed nucleus of stria terminalis (BST), urocortin 1 (Ucn1) neurons of centrally projecting Edinger-Westphal nucleus (cpEW) and serotonin (5HT) cells of dorsal raphe (DR) in PACAP deficiency. CVMS caused decreased body weight and increased adrenal size, corticosterone (CORT) titers and depression-like behavior in WT mice, in contrast to KO animals. CVMS increased FosB in the central (CeA) and medial amygdala, dorsomedial (dmBST), ventral (vBST), ovBST, CA1 area, dentate gyrus (DG), ventral lateral septum, parvo- (pPVN) and magnocellular paraventricular nucleus, lateral periaqueductal gray, cpEW and DR. Lack of PACAP blunted the CVMS-induced FosB rise in the CeA, ovBST, dmBST, vBST, CA1 area, pPVN and DR. The CVMS-induced FosB expression in ovBST-CRF and cpEW-Ucn1 neurons was abolished in KO mice. Although CVMS did not induce FosB in 5HT-DR neurons, PACAP KO mice had increased 5HT cell counts and 5HT content. We conclude that PACAP deficiency affects neuronal reactivity in a brain area-specific manner in stress centers, as well as in ovBST CRF, cpEW-Ucn1 and 5HT-DR neurons leading to reduced CVMS response and altered depression level. PMID- 27282085 TI - The neural underpinnings of cognitive flexibility and their disruption in psychotic illness. AB - Schizophrenia (SZ) has long been associated with a variety of cognitive deficits, including reduced cognitive flexibility. More recent findings, however, point to tremendous inter-individual variability among patients on measures of cognitive flexibility/set-shifting. With an eye toward shedding light on potential sources of variability in set-shifting abilities among SZ patients, I examine the neural substrates of underlying probabilistic reversal learning (PRL) - a paradigmatic measure of cognitive flexibility - as well as neuromodulatory influences upon these systems. Finally, I report on behavioral and neuroimaging studies of PRL in SZ patients, discussing the potentially influences of illness profile and antipsychotic medications on cognitive flexibility in SZ. PMID- 27282088 TI - Lipid-Based Therapy for Ocular Surface Inflammation and Disease. PMID- 27282089 TI - Modelling Adaptive Learning Behaviours for Consensus Formation in Human Societies. AB - Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people's adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics. PMID- 27282090 TI - Current role for spa therapy in rheumatology. PMID- 27282091 TI - Current role for bone absorptiometry. AB - Bone mineral density (BMD) measurement using dual-energy X-ray absorptiometry (DXA) is a key contributor to the management of bone fragility syndromes, most notably postmenopausal osteoporosis. Experimental studies of bone biomechanics have established that an accurate marker for mechanical strength is areal BMD (aBMD, g/cm2). Areal BMD contributes 70% of mechanical strength at the femur and 40% at the spine. Two decades after the T-score was first introduced (World Health Organization, 1994), changes have occurred in the indications of DXA and in the interpretation of its results for the diagnosis, prognosis, and treatment of osteoporosis. PMID- 27282092 TI - Sleeping difficulties and health-related quality of life in Parkinson's disease. AB - OBJECTIVE: Various sleep-related symptoms occur in Parkinson's disease (PD). Their occurrence with health-related quality of life (HRQL), comorbid sleep disorders, and other comorbidities was studied. METHODS: Altogether, 1447 randomly selected patients with Parkinson's disease, aged 43-89 years, participated in a questionnaire study. A structured questionnaire with 207 items was based on the Basic Nordic Sleep Questionnaire. Questions on demographics, PD, sleep disorders, and comorbidities were included. RESULTS: The response rate was 59.0%, and of these, 80% had answered to all questions that were used in the analyses (N=684). Occurrence of long sleep was found in 26.2% of the subjects, short sleep in 32.5%, poor sleep in 21.2%, sleep deprivation in 33.8%, disrupted sleep in 47.4%, and difficulties to fall asleep in 12.2%, respectively. Poor self rated health and poor quality of life occurred in 44.4% and in 43.3% of all participants. In the logistic regression, age and gender differentially predicted long sleep and sleep deprivation, such that older age and being male were positively associated with long sleep but negatively associated with the report of sleep deprivation. Depression, subjective negative stress, and fatigue occurred with long sleep. On the other hand, poor sleep and excessive daytime sleepiness occurred with short sleep and sleep deprivation. CONCLUSIONS: The sleep difficulties in PD are frequent. The long sleeping patients have depression, stress, and fatigue. PMID- 27282093 TI - Pulsed electromagnetic field therapy improves tendon-to-bone healing in a rat rotator cuff repair model. AB - Rotator cuff tears are common musculoskeletal injuries often requiring surgical intervention with high failure rates. Currently, pulsed electromagnetic fields (PEMFs) are used for treatment of long-bone fracture and lumbar and cervical spine fusion surgery. Clinical studies examining the effects of PEMF on soft tissue healing show promising results. Therefore, we investigated the role of PEMF on rotator cuff healing using a rat rotator cuff repair model. We hypothesized that PEMF exposure following rotator cuff repair would improve tendon mechanical properties, tissue morphology, and alter in vivo joint function. Seventy adult male Sprague-Dawley rats were assigned to three groups: bilateral repair with PEMF (n = 30), bilateral repair followed by cage activity (n = 30), and uninjured control with cage activity (n = 10). Rats in the surgical groups were sacrificed at 4, 8, and 16 weeks. Control group was sacrificed at 8 weeks. Passive joint mechanics and gait analysis were assessed over time. Biomechanical analysis and MUCT was performed on left shoulders; histological analysis on right shoulders. Results indicate no differences in passive joint mechanics and ambulation. At 4 weeks the PEMF group had decreased cross-sectional area and increased modulus and maximum stress. At 8 weeks the PEMF group had increased modulus and more rounded cells in the midsubstance. At 16 weeks the PEMF group had improved bone quality. Therefore, results indicate that PEMF improves early tendon healing and does not alter joint function in a rat rotator cuff repair model. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:902-909, 2017. PMID- 27282094 TI - Current knowledge of sand fly fauna (Diptera: Psychodidae) of northwestern Yemen and how it relates to leishmaniasis transmission. AB - This report presents the results of the first entomological survey of the sand fly fauna in northwestern Yemen. Sand flies were collected using sticky paper traps and CDC light traps from Hajjah governorate, a cutaneous leishmaniasis focus due to Leishmania tropica. Six Phlebotomus species: P. alexandri, P. arabicus. P. bergeroti, P. orientalis, P. papatasi, P. sergenti and ten Sergentomyia species: S. africana, S. antennata, S. christophersi, S. dolichopa, S. dreyfussi, S. fallax, S. multidens, S. taizi, S. tiberiadis, S. yusafi were identified. P. alexandri was the most predominant Phlebotomus species and P. papatasi was a scarce species. S. fallax was the principal Sergentomyia species and S. dolichopa was the least species encountered. The diversity of the sand fly fauna within and among three altitudinal ranges using Simpson index and Jaccard's diversity coefficient respectively were measured. High species diversity was found in all altitude ranges. There seemed to be more association between sand fly fauna in higher altitudes with fauna from moderate altitudes. Sand fly seasonal activity showed a mono-modal trend in the lowland and a confluent bimodal trend in the highlands. Leishmania DNA could not be detected from 150 Phlebotomus females using PCR-RFLP. A possible zoonotic cutaneous transmission cycle due to Leishmania tropica in northwestern Yemen would involve P. arabicus as the sand fly vector and the rock hyrax as the reservoir host. The vector competence for P. alexandri as a vector of visceral leishmaniasis in Hajjah governorate is discussed. PMID- 27282095 TI - Molecular and serological characterization of the first Leptospira santarosai strain isolated from a dog. AB - Leptospirosis is a zoonotic disease of global importance caused by pathogenic Leptospira species. Dogs can become asymptomatically infected, acting like reservoir hosts for pathogenic Leptospira, notably Leptospira interrogans serovar Canicola. Identification of such individuals and characterization of leptospires involved in chronic infections may unravel the role of dogs in the epidemiology of particular leptospiral strains. The aim of the present work was to describe the first Leptospira santarosai strain isolated from a dog. The dog was kept in a public shelter in Sao Paulo city, Brazil, and presented asymptomatic urinary shedding detected by PCR. Prospective evaluation was performed to fully characterize its chronic carrier state. The dog did not present anti-Leptospira titles or clinical/laboratorial abnormalities during the evaluations; nevertheless long-term urinary shedding was confirmed by PCR and leptospires were recovered from two occasions. The isolated strain was molecularly characterized by partial 16S rRNA and secY gene sequencing and MLST analysis. Serogroup identification was performed using polyclonal antibodies. The strain was identified as Leptospira santarosai, serogroup Sejroe. This is the first evidence in the literature of the isolation of L. santarosai in dogs. Our findings show that dogs can persistently harbor leptospires other than L. interrogans. PMID- 27282097 TI - Morphology and identification of first instar larvae of Australian blowflies of the genus Chrysomya of forensic importance. AB - Light microscopy photographs, line illustrations and scanning electron microscopy micrographs are provided for first instar larvae of six Australian species of Chrysomya. All species have confirmed or potential in forensic investigations given their carrion-breeding habits. Morphology of the first instar larvae of Ch. nigripes, Ch. rufifacies, Ch. saffranea and Ch. varipes is revised, while larvae of Ch. incisularis and Ch. latifrons are described for the first time. The following morphological structures are documented: pseudocephalon, antennal complex, maxillary palpus, facial mask, thoracic and abdominal spinulation, spiracular field, posterior spiracles and cephaloskeleton. New diagnostic features of the cephaloskeleton and the spinulation of the abdominal segments are described. Verification of earlier descriptions revealed major discrepancies between published data, especially in the case of Ch. nigripes. The present results allow clarification, correction and, especially, complementation of the existing information provided by numerous authors. Finally, an identification key for first instar larvae of Australian necrophagous Chrysomya is presented. PMID- 27282096 TI - Evidence for natural vertical transmission of chikungunya viruses in field populations of Aedes aegypti in Delhi and Haryana states in India-a preliminary report. AB - Aedes aegypti and Aedes albopictus are principal vectors for the transmission of chikungunya virus (CHIKV). India is a hub for both dengue and chikungunya infections and there are several reports of co-infection of dengue and chikungunya virus in the clinical scenario. The present pilot entomological survey was conducted to evaluate vertical transmission of CHIKV in Aedes field populations. Aedes immature (larvae and pupae) collection was done in 2012, over a period of six months from selected sites in Delhi and Haryana, India. The immatures collected were reared for adult emergence and species identification was done. A. aegypti male and female mosquitoes were separated and pooled collection spot-wise, RNA extracted and RT PCR performed to test for the presence of CHIKV in the pools. Container index (CI) and minimum infection rate (MIR) were estimated. From study areas that tested positive for CHIKV, adult collections were made and females upon feeding on uninfected blood in laboratory were allowed to lay eggs. The progeny that emerged from these field-collected mothers were tested for CHIKV presence. Our pilot survey showed the existence of A. aegypti population even during peak summer season in a few foci which eventually helped the mosquitoes to tide over adverse environmental conditions and with the start of rainfall, the population exploded within a short period of time. Immatures collected from field and progeny of adults collected from the field were CHIKV positive demonstrating the presence of vertical transmission of chikungunya virus in field population of A. aegypti. The present study further demonstrates the importance of identifying permanent breeding sites for proper Aedes species control. PMID- 27282098 TI - Genetics, cross-resistance and synergism of indoxacarb resistance in Helicoverpa armigera (Lepidoptera: Noctuidae). AB - BACKGROUND: The cotton bollworm Helicoverpa armigera is a global pest of field and horticultural crops and has developed resistance to insecticides from many chemical classes. Indoxacarb is an important option for selective control of H. armigera in a range of crops that play host to this species. A strain of H. armigera resistant to indoxacarb (designated GY7-39) was detected from the field by F2 screening and characterised by comparison with a near-isogenic indoxacarb susceptible laboratory strain to determine inheritance, cross-resistance profile and synergism of indoxacarb resistance. RESULTS: The level of indoxacarb resistance in the GY7-39 strain was 139-198-fold compared with the susceptible strain. Genetic analysis showed that resistance was autosomal, incompletely dominant and conferred by one or a few closely linked loci. Indoxacarb resistance in the GY7-39 strain did not confer cross-resistance to chlorantraniliprole. The GY7-39 strain was more susceptible to emamectin benzoate, fenvalerate, Cry1Ac and Cry2Ab compared with the susceptible strain. Indoxacarb resistance was synergised by the metabolic inhibitor PBO. CONCLUSIONS: Rapid selection of indoxacarb resistance in the GY7-39 strain indicates the potential risk of resistance development to indoxacarb in field populations of H. armigera. Lack of cross resistance indicates that resistance could be managed effectively by the use of rotational strategies that incorporate transgenic technologies. Synergism studies indicate the potential involvement of metabolic detoxification enzymes as the mechanism of resistance to indoxacarb. (c) 2016 Society of Chemical Industry. PMID- 27282099 TI - Higher visceral to subcutaneous fat ratio is associated with small intestinal bacterial overgrowth. AB - BACKGROUND AND AIMS: There is a lack of studies evaluating the association between small intestinal bacterial overgrowth (SIBO) and abdominal fat. The aim of this study was to evaluate whether visceral fat area (VFA), subcutaneous fat area (SFA) or visceral to subcutaneous fat ratio (VFA/SFA ratio) were associated with SIBO. METHODS AND RESULTS: In this case-control study, 152 eligible patients submitted to glucose hydrogen/methane breath test who also had computed tomography (CT) of the abdomen performed were included. Clinical and demographic information was obtained. VFA and SFA were measured using Image J software at lumbar 3 level on CT cross-sectional image of the 152 patients included in this study, 68 patients (44.7%) tested positive for SIBO. In the univariate analysis, the presence of SIBO was associated with older age (65.2 +/- 1.5 vs. 59.3 +/- 1.5, p = 0.007); type 2 diabetes mellitus (33.8% vs. 17.9%; p = 0.019); hypertension (63.2% vs. 39.3%; p = 0.003); metabolic syndrome (85.3% vs. 64.3%; p = 0.003); and higher VFA/SFA ratio (1.0 +/- 0.1 vs. 0.7 +/- 0.1; p < 0.001). In multivariate analysis, metabolic syndrome (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p = 0.035) and higher VFA/SFA ratio (OR: 3.3; 95% CI: 1.6 7.2; p = 0.002) remained independently associated with SIBO. CONCLUSION: The presence of SIBO was found to be associated with high VFA/SFA ratio measured from cross-sectional CT image. PMID- 27282100 TI - Monitoring of multiple bacteriocins through a developed dual extraction protocol and comparison of HPLC-DAD with turbidometry as their quantification system. AB - The present study describes the development of a simple and efficient screening system that allows identification and quantification of nine bacteriocins produced by Lactococcus lactis. Cell-free L. lactis extracts presented a broad spectrum of antibacterial activity, including Gram-negative bacteria, Gram positive bacteria, and fungi. The characterization of their sensitivity to pH, and heat, showed that the extracts retained their antibacterial activity at extreme pH values and in a wide temperature range. The loss of antibacterial activity following treatment of the extracts with lipase or protease suggests a lipoproteinaceous nature of the produced antimicrobials. The extracts were subjected to a purification protocol that employs a two phase extraction using ammonium sulfate precipitation and organic solvent precipitation, followed by ion exchange chromatography, solid phase extraction and HPLC. In the nine fractions that presented antimicrobial activity, bacteriocins were quantified by the turbidometric method using a standard curve of nisin and by the HPLC method with nisin as the external standard, with both methods producing comparable results. Turbidometry appears to be unique in the qualitative determination of bacteriocins but the only method suitable to both separate and quantify the bacteriocins providing increased sensitivity, accuracy, and precision is HPLC. PMID- 27282101 TI - Evaluation of 16S rRNA amplicon sequencing using two next-generation sequencing technologies for phylogenetic analysis of the rumen bacterial community in steers. AB - Next generation sequencing technologies have vastly changed the approach of sequencing of the 16S rRNA gene for studies in microbial ecology. Three distinct technologies are available for large-scale 16S sequencing. All three are subject to biases introduced by sequencing error rates, amplification primer selection, and read length, which can affect the apparent microbial community. In this study, we compared short read 16S rRNA variable regions, V1-V3, with that of near full length 16S regions, V1-V8, using highly diverse steer rumen microbial communities, in order to examine the impact of technology selection on phylogenetic profiles. Short paired-end reads from the Illumina MiSeq platform were used to generate V1-V3 sequence, while long "circular consensus" reads from the Pacific Biosciences RSII instrument were used to generate V1-V8 data. The two platforms revealed similar microbial operational taxonomic units (OTUs), as well as similar species richness, Good's coverage, and Shannon diversity metrics. However, the V1-V8 amplified ruminal community resulted in significant increases in several orders of taxa, such as phyla Proteobacteria and Verrucomicrobia (P < 0.05). Taxonomic classification accuracy was also greater in the near full-length read. UniFrac distance matrices using jackknifed UPGMA clustering also noted differences between the communities. These data support the consensus that longer reads result in a finer phylogenetic resolution that may not be achieved by shorter 16S rRNA gene fragments. Our work on the cattle rumen bacterial community demonstrates that utilizing near full-length 16S reads may be useful in conducting a more thorough study, or for developing a niche-specific database to use in analyzing data from shorter read technologies when budgetary constraints preclude use of near-full length 16S sequencing. PMID- 27282103 TI - Corrigendum: Interaction between V-ATPase B2 and (Pro) renin Receptors in Promoting the progression of Renal Tubulointerstitial Fibrosis. PMID- 27282102 TI - Spectral properties of bacteriophytochrome AM1_5894 in the chlorophyll d containing cyanobacterium Acaryochloris marina. AB - Acaryochloris marina, a unicellular oxygenic photosynthetic cyanobacterium, has uniquely adapted to far-red light-enriched environments using red-shifted chlorophyll d. To understand red-light use in Acaryochloris, the genome of this cyanobacterium was searched for red/far-red light photoreceptors from the phytochrome family, resulting in identification of a putative bacteriophytochrome AM1_5894. AM1_5894 contains three standard domains of photosensory components as well as a putative C-terminal signal transduction component consisting of a histidine kinase and receiver domain. The photosensory domains of AM1_5894 autocatalytically assemble with biliverdin in a covalent fashion. This assembled AM1_5894 shows the typical photoreversible conversion of bacterial phytochromes with a ground-state red-light absorbing (Pr) form with lambdaBV max[Pr] 705 nm, and a red-light inducible far-red light absorbing (Pfr) form with lambdaBV max[Pfr] 758 nm. Surprisingly, AM1_5894 also autocatalytically assembles with phycocyanobilin, involving photoreversible conversion of lambdaPCB max[Pr] 682 nm and lambdaPCB max[Pfr] 734 nm, respectively. Our results suggest phycocyanobilin is also covalently bound to AM1_5894, while mutation of a cysteine residue (Cys11Ser) abolishes this covalent binding. The physiological function of AM1_5894 in cyanobacteria containing red-shifted chlorophylls is discussed. PMID- 27282104 TI - New Insights into the Biology of the BDNF Transcriptional 'Code'. PMID- 27282105 TI - Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease. PMID- 27282106 TI - RBP2 induces stem-like cancer cells by promoting EMT and is a prognostic marker for renal cell carcinoma. AB - Renal cell carcinoma (RCC), one of the most common kidney cancers, has a poor prognosis. Epithelial to mesenchymal transition (EMT) is a hallmark of carcinoma invasion and metastasis. Several studies have examined the molecular regulation of EMT, but the relationship between histone demethylases and EMT is little understood. In this study, we investigated the role of retinoblastoma-binding protein-2 (RBP2), a histone demethylase that is highly expressed in RCC and is positively correlated with poor RCC prognosis in the regulation of EMT. We found that ectopic overexpression of RBP2 can induce cancer stem cell-like (CSC) phenotypes through EMT in RCC cells by converting them to a more mesenchymal phenotype. This results in increased resistance to apoptosis, which leads to enhanced tumor growth in xenograft models. Together, our data show that RBP2 is an epigenetic regulator that has an important role in the initiation of CSC phenotypes through EMT, leading to tumor progression. RBP2 is also a novel biomolecule for RCC diagnosis, and prognosis and may be a therapeutic target. PMID- 27282108 TI - Comparison of deep neural networks to spatio-temporal cortical dynamics of human visual object recognition reveals hierarchical correspondence. AB - The complex multi-stage architecture of cortical visual pathways provides the neural basis for efficient visual object recognition in humans. However, the stage-wise computations therein remain poorly understood. Here, we compared temporal (magnetoencephalography) and spatial (functional MRI) visual brain representations with representations in an artificial deep neural network (DNN) tuned to the statistics of real-world visual recognition. We showed that the DNN captured the stages of human visual processing in both time and space from early visual areas towards the dorsal and ventral streams. Further investigation of crucial DNN parameters revealed that while model architecture was important, training on real-world categorization was necessary to enforce spatio-temporal hierarchical relationships with the brain. Together our results provide an algorithmically informed view on the spatio-temporal dynamics of visual object recognition in the human visual brain. PMID- 27282109 TI - Trends analyses of 30 years of ambient 8 hour ozone and precursor monitoring data in the South Central U.S.: progress and challenges. AB - In the last 30 years ambient ozone concentrations have notably decreased in the South Central U.S. Yet, current ambient ozone concentrations measured over the past three years 2013-2015 in this area of the U.S. are not meeting the U.S. 2015 8 hour ozone standard of 70 parts per billion (ppb). This paper provides an update on long-term trends analyses of ambient 8 hour ozone and ozone precursor monitoring data collected over the past 30 years (1986-2015) in four South Central U.S. cities, following up on two previously published reviews of 20 and 25 year trends for these cities. All four cities have benefitted from national ozone precursor controls put in place during the 1990s and 2000s involving cleaner vehicles (vehicle fleet turnover/replacement over time), cleaner fuels, cleaner gasoline and diesel engines, and improved inspection/maintenance programs for existing vehicles. Additional ozone precursor emission controls specific to each city are detailed in this paper. The controls have resulted in impressive ambient ozone and ambient ozone precursor concentration reductions in the four South Central U.S. cities over the past 30 years, including 31-70% ambient nitrogen oxides (NOx) concentration declines from historical peaks to the present, 43-72% volatile organic compound (VOC) concentration declines from historical peaks to the present, a related 45-76% VOC reactivity decline for a subset of VOC species from historical peaks to the present, and an 18-38 ppb reduction in city 8 hour ozone design value concentrations. A new challenge for each of the four South Central U.S. cities will be meeting the U.S. 2015 8 hour ozone standard of 70 ppb. PMID- 27282107 TI - Somatic mutations in disorders with disrupted brain connectivity. AB - Mutations occur during cell division in all somatic lineages. Because neurogenesis persists throughout human life, somatic mutations in the brain arise during development and accumulate with the aging process. The human brain consists of 100 billion neurons that form an extraordinarily intricate network of connections to achieve higher level cognitive functions. Due to this network architecture, perturbed neuronal functions are rarely restricted to a focal area; instead, they are often spread via the neuronal network to affect other connected areas. Although somatic diversity is an evident feature of the brain, the extent to which somatic mutations affect the neuronal structure and function and their contribution to neurological disorders associated with disrupted brain connectivity remain largely unexplored. Notably, recent reports indicate that brain somatic mutations can indeed play a critical role that leads to the structural and functional abnormalities of the brain observed in several neurodevelopmental disorders. Here, I review the extent and significance of brain somatic mutations and provide my perspective regarding these mutations as potential molecular lesions underlying relatively common conditions with disrupted brain connectivity. Moreover, I discuss emerging technical platforms that will facilitate the detection of low-frequency somatic mutations and validate the biological functions of the identified mutations in the context of brain connectivity. PMID- 27282110 TI - Prospective Randomized Comparison of Knee Stability and Proprioception for Posterior Cruciate Ligament Reconstruction With Autograft, Hybrid Graft, and gamma-Irradiated Allograft. AB - PURPOSE: To evaluate posterior stability and proprioception after arthroscopic posterior cruciate ligament reconstruction with autograft, hybrid graft, and gamma-irradiated allograft. METHODS: This prospective, randomized controlled trial (with 5 years' follow-up) included 90 patients who underwent posterior cruciate ligament reconstruction with autograft (gracilis and semitendinosus tendons), hybrid graft (gamma-irradiated tibialis anterior tendon allograft and semitendinosus tendon autograft), or gamma-irradiated allograft (tibialis anterior tendons). All the gamma-irradiated allografts (tibialis anterior tendons) received an irradiation dose of 2.5 Mrad before distribution. Patients in this study had undergone a preoperative magnetic resonance imaging scan and physical examination. Patients were excluded from the study if they had a concomitant injury to other knee ligaments, previous surgery on the injured knee, or articular cartilage lesions greater than Outerbridge grade II. Clinical and proprioceptive evaluation results were collected preoperatively and at 3, 6, 12, 24, 36, and 60 months after surgery. RESULTS: The autograft, allograft, and hybrid graft groups were followed up for 5.5 +/- 0.2 months (range, 5 to 6 years), 5.7 +/- 0.3 months (range, 5 to 6 years), and 5.6 +/- 0.5 months (range, 5 to 6 years), respectively. No statistically significant differences were found among the 3 groups regarding preoperative demographic factors (P > .05). The differences in physical examination findings and subjective evaluations among the 3 groups were not significant (P > .05). However, a significant difference was detected in instrumented anteroposterior measurements, with more laxity shown in the gamma-irradiated allograft group than in the other 2 groups (P = .006). CONCLUSIONS: The differences in proprioceptive and functional outcomes among the 3 groups were not significant. In contrast, a significant difference was detected in instrumented anteroposterior measurements, which showed more laxity in the gamma-irradiated allograft group than in the other 2 groups. However, this may not be clinically significant. LEVEL OF EVIDENCE: Level II, prospective comparative study. PMID- 27282111 TI - The Effect of Purified Human Bone Marrow-Derived Mesenchymal Stem Cells on Rotator Cuff Tendon Healing in an Athymic Rat. AB - PURPOSE: To evaluate the ability of purified human bone marrow-derived mesenchymal stem cells (MSCs) to augment healing of an acute small- to medium sized rotator cuff repair in a small-animal model, evaluating the structure and composition of the healing tendon-bone interface with histologic and biomechanical analyses. METHODS: Fifty-two athymic rats underwent unilateral detachment and transosseous repair of the supraspinatus tendon augmented with either fibrin glue (control group) or fibrin glue with 106 human MSCs (experimental group) applied at the repair site. Flow cytometry verified the stem cell phenotype of the cells as CD73+, CD90+, CD105+, CD14-, CD34-, and CD45-. Rats were killed at 2 and 4 weeks, with 10 from each group used for biomechanical testing and 3 for histologic analysis. RESULTS: Safranin O staining identified increased fibrocartilage formation at the repair site at 2 weeks in the human MSC group (18.6% +/- 2.9% vs 9.1% +/- 1.6%, P = .026). Picrosirius staining identified decreased energy (36.88 +/- 4.99 J vs 54.97 +/- 8.33 J, P = .04) and increased coherence in the human MSC group (26.96% +/- 15.32% vs 14.53% +/- 4.10%, P = .05), indicating improved collagen orientation. Biomechanical testing showed a significant increase in failure load (11.5 +/- 2.4 N vs 8.5 +/- 2.4 N, P = .002) and stiffness (7.1 +/- 1.2 N/mm vs 5.7 +/- 2.1 N/mm, P < .001) in the experimental group compared with the control group at 2 weeks. These effects dissipated by 4 weeks, with no significant differences in fibrocartilage formation (35% +/- 5.0% vs 26.6% +/- 0.6%, P = .172) or biomechanical load to failure (24.6 +/- 7.1 N vs 21.5 +/- 4.1 N, P = .361) or stiffness (13.5 +/- 3.1 N/mm vs 16.1 +/- 5.6 N/mm, P = .384). All failures occurred at the bone-tendon interface. CONCLUSIONS: Rotator cuff repair augmentation with purified human MSCs improved early histologic appearance and biomechanical strength of the repair at 2 weeks, although the effects dissipated by 4 weeks with no significant differences between groups. CLINICAL RELEVANCE: Human MSCs may improve early rotator cuff healing during the first 2 weeks after repair. PMID- 27282112 TI - Para-allopatry in hybridizing fire-bellied toads (Bombina bombina and B. variegata): Inference from transcriptome-wide coalescence analyses. AB - Ancient origins, profound ecological divergence, and extensive hybridization make the fire-bellied toads Bombina bombina and B. variegata (Anura: Bombinatoridae) an intriguing test case of ecological speciation. Previous modeling has proposed that the narrow Bombina hybrid zones represent strong barriers to neutral introgression. We test this prediction by inferring the rate of gene exchange between pure populations on either side of the intensively studied Krakow transect. We developed a method to extract high confidence sets of orthologous genes from de novo transcriptome assemblies, fitted a range of divergence models to these data and assessed their relative support with analytic likelihood calculations. There was clear evidence for postdivergence gene flow, but, as expected, no perceptible signal of recent introgression via the nearby hybrid zone. The analysis of two additional Bombina taxa (B. v. scabra and B. orientalis) validated our parameter estimates against a larger set of prior expectations. Despite substantial cumulative introgression over millions of years, adaptive divergence of the hybridizing taxa is essentially unaffected by their lack of reproductive isolation. Extended distribution ranges also buffer them against small-scale environmental perturbations that have been shown to reverse the speciation process in other, more recent ecotypes. PMID- 27282114 TI - Outcomes of halo immobilization in the management of subaxial cervical facet fractures. AB - BACKGROUND: Spinal injury causes a significant burden on patients, families and health services. Cervical facet fractures are uncommon, and there is a paucity of functional and health-related quality-of-life data in patients who are managed non-operatively for this injury. METHODS: Victorian State Trauma Registry patients managed in a halothoracic brace for cervical facet injuries from August 2006 to June 2013 were included. Health status (12-item Short-Form health survey), function (Glasgow Outcome Scale-Extended), pain and return to work outcomes were assessed at 6, 12 and 24 months post-injury. Subgroup analysis was performed for age, sex, comorbidity, compensable status, Injury Severity Score (ISS) and education. RESULTS: Outcome data were available for 54 patients, with road trauma being the most common mechanism (69%), followed by a fall from height (18%). Overall, good 24-month function was achieved in 35% of patients, and 51% and 77% of patients reported good physical and mental health status, respectively. Ongoing moderate-severe neck pain was present in 19% of patients. Poorer function was associated with compensable status (P = 0.05), an ISS > 12 (P = 0.001) and a lower level of education (P = 0.04). Poorer physical health status was associated with age >=50 (P = 0.05), pre-existing comorbidities, an ISS > 12 (P = 0.04) and a lower level of education (P = 0.03). CONCLUSION: Although many patients achieved good function and health status by 24 months, neck pain remains prevalent. A number of demographic factors were associated with a poorer outcome. This understanding helps to inform prognosis when managing this injury. PMID- 27282113 TI - New therapeutic and diagnostic opportunities for injured tissue-specific targeting of complement inhibitors and imaging modalities. AB - Despite substantial opportunity and commercial interest in developing drugs that modulate the complement system in a broad range of non-orphan indications, several obstacles remain to be overcome. Among these issues is the biophysical nature of complement proteins, whose circulating levels are typically very high and whose turnover rates are relatively rapid, especially in the setting of chronic inflammatory conditions. This situation necessitates the use of very high levels of therapeutic compounds in order to achieve both multi-pathway and multiple effector mechanism inhibition. In addition, one must avoid infectious complications or the systemic impairment of the other important physiological functions of complement. Herein we focus on the development of a novel therapeutic strategy based on injured tissue-specific targeting of complement inhibitors using the antigen-combining domains of a small subset of natural IgM antibodies, which as endogenous antibodies specifically recognize sites of local damage across a broad range of tissues and locally activate complement C3, resulting in C3 fragment covalent fixation. Because the use of such recombinant tissue-targeting inhibitors precludes the utility of measuring systemic levels of complement biomarkers or function, since a goal of this targeting strategy is to leave those processes intact and unimpeded, we also briefly describe a new method designed to quantitatively measure using imaging modalities the inhibition of generation of fixed C3 fragments at sites of inflammation/injury. In addition to the ability to determine whether complement activation is locally constrained with the use of inhibitors, there is also a broader application of this imaging approach to inflammatory and autoimmune diseases characterized by local complement activation. PMID- 27282115 TI - Barriers and Facilitation Measures Related to People With Mental Disorders When Using the Web: A Systematic Review. AB - BACKGROUND: Mental disorders (MDs) affect almost 1 in 4 adults at some point during their lifetime, and coupled with substance use disorders are the fifth leading cause of disability adjusted life years worldwide. People with these disorders often use the Web as an informational resource, platform for convenient self-directed treatment, and a means for many other kinds of support. However, some features of the Web can potentially erect barriers for this group that limit their access to these benefits, and there is a lack of research looking into this eventuality. Therefore, it is important to identify gaps in knowledge about "what" barriers exist and "how" they could be addressed so that this knowledge can inform Web professionals who aim to ensure the Web is inclusive to this population. OBJECTIVE: The objective of this study was to provide an overview of existing evidence regarding the barriers people with mental disorders experience when using the Web and the facilitation measures used to address such barriers. METHODS: This study involved a systematic review of studies that have considered the difficulties people with mental disorders experience when using digital technologies. Digital technologies were included because knowledge about any barriers here would likely be also applicable to the Web. A synthesis was performed by categorizing data according to the 4 foundational principles of Web accessibility as proposed by the World Wide Web Consortium, which forms the necessary basis for anyone to gain adequate access to the Web. Facilitation measures recommended by studies were later summarized into a set of minimal recommendations. RESULTS: A total of 16 publications were included in this review, comprising 13 studies and 3 international guidelines. Findings suggest that people with mental disorders experience barriers that limit how they perceive, understand, and operate websites. Identified facilitation measures target these barriers in addition to ensuring that Web content can be reliably interpreted by a wide range of user applications. CONCLUSIONS: People with mental disorders encounter barriers on the Web, and attempts have been made to remove or reduce these barriers. As forewarned by experts in the area, only a few studies investigating this issue were found. More rigorous research is needed to be exhaustive and to have a larger impact on improving the Web for people with mental disorders. PMID- 27282116 TI - Molecular evaluation of vitamin D responsiveness of healthy young adults. AB - Vitamin D3 has via its metabolites 25-hydroxyvitamin D3 (25(OH)D3) and 1alpha,25 dihydroxyvitamin D3 (1,25(OH)2D3) direct effects on the transcriptome and the epigenome of most human cells. In the VitDbol study we exposed 35 healthy young adults to an oral vitamin D3 dose (2000MUg) or placebo and took blood samples directly before the supplementation as well as at days 1, 2 and 30. Within 24h the vitamin D3 intake raised the average serum levels of both 25(OH)D3 and 1,25(OH)2D3 by approximately 20%. However, we observed large inter-individual differences in these serum levels, reflected by the average ratios between 25(OH)D3 and 1,25(OH)2D3 concentrations ranging from 277 to 1365. Interestingly, average serum parathyroid hormone (PTH) levels increased at day 1 by some 10% but then decreased within the following four weeks to levels 5% below baseline. In peripheral blood mononuclear cells (PBMCs) that were isolated at the same time points we determined vitamin D-modulated chromatin accessibility by FAIRE-qPCR at selected genomic loci. This method is well suited to evaluate both short-term and long-term in vivo effects of vitamin D on the epigenome of human subjects. The differential vitamin D responsiveness of the VitDbol study participants was determined via individual changes in their PTH levels or chromatin accessibility in relation to alterations in 25(OH)D3 concentrations. This led to the segregation of the subjects into 14 high, 11 mid and 10 low responders. In summary, the vitamin D responsiveness classification provides additional information compared to a vitamin D status assessment based on single 25(OH)D3 serum measurements. The study was registered at Clinicaltrials.gov (NCT02063334). PMID- 27282117 TI - Interim methadone and patient navigation in jail: Rationale and design of a randomized clinical trial. AB - BACKGROUND: Methadone maintenance is an effective treatment for opioid dependence but is rarely initiated in US jails. Patient navigation is a promising approach to improve continuity of care but has not been tested in bridging the gap between jail- and community-based drug treatment programs. METHODS: This is an open-label randomized clinical trial among 300 adult opioid dependent newly-arrested detainees that will compare three treatment conditions: methadone maintenance without routine counseling (termed Interim Methadone; IM) initiated in jail v. IM and patient navigation v. enhanced treatment-as-usual. The two primary outcomes will be: (1) the rate of entry into treatment for opioid use disorder within 30days from release and (2) frequency of opioid positive urine tests over the 12 month follow-up period. An economic analysis will examine the costs, cost effectiveness, and cost-benefit ratio of the study interventions. RESULTS: We describe the background and rationale for the study, its aims, hypotheses, and study design. CONCLUSIONS: Given the large number of opioid dependent detainees in the US and elsewhere, initiating IM at the time of incarceration could be a significant public health and clinical approach to reducing relapse, recidivism, HIV-risk behavior, and criminal behavior. An economic analysis will be conducted to assist policy makers in determining the utility of adopting this approach. ClinicalTrials.gov: NCT02334215. PMID- 27282118 TI - Injectable pharmacotherapy for opioid use disorders (IPOD). AB - BACKGROUND: Despite the growing prevalence of opioid use among offenders, pharmacotherapy remains an underused treatment approach in correctional settings. The aim of this 4-year trial is to assess the clinical utility, effectiveness, and cost implications of extended-release naltrexone (XR-NTX, Vivitrol(r); Alkermes Inc.) alone and in conjunction with patient navigation for jail inmates with opioid use disorder (OUD). METHODS: Opioid-dependent inmates will be randomly assigned to one of three treatment conditions before being released to the community to include: 1) XR-NTX only; 2) XR-NTX plus patient navigation (PN), and 3) enhanced treatment-as-usual (ETAU) with drug education and a community treatment referral. Before release from jail, participants in the XR-NTX and XR NTX plus PN conditions will receive their first XR-NTX injection. Those in the XR NTX plus PN condition also will meet with a patient navigator. Participants in both XR-NTX conditions will be scheduled for medical management sessions twice monthly for months 1-3, monthly medical management sessions for months 4-6, with monthly injections for 5months post-release (which, given the pre-release injection, results in a 6-month medication phase). Follow-up data collection will occur at 1, 3, 6, and 12months post release. RESULTS: We discuss the study's rationale, aims, methods, and anticipated findings. The primary outcome is the presence of a DSM 5 OUD diagnosis 1year after randomization (6months after the end of the active treatment phase). DISCUSSION: We hypothesize that providing XR NTX prior to release from jail will be particularly beneficial for this extremely high-risk population by reducing opioid use, associated criminal behavior, and injection-related disease risk. ClinicalTrials.Gov: NCT02110264. PMID- 27282119 TI - The OPTIMIZE trial: Rationale and design of a randomized controlled trial of motivational enhancement therapy to improve adherence to statin medication. AB - BACKGROUND: Statins are a class of medications that are particularly effective for lowering cholesterol and reducing cardiovascular morbidity and mortality. Despite a range of benefits, non-adherence to statin medication is prevalent with 50% to 75% of patients failing to adhere to treatment within the first 2-years. A previous review on interventions to improve adherence to cholesterol lowering medication concluded that rigorous trials were needed with emphasis on the patient's perspective and shared decision making. Motivational interviewing (MInt) is a promising patient-centered approach for improving adherence in patients with chronic diseases. This manuscript describes the rational and design of a randomized controlled trial (RCT) testing the efficacy of MInt in improving adherence to statin medication. METHODS: Patients filling their first statin prescription will be recruited to complete a 6-month observation run-in period (phase-1) after which medication possession ratio (MPR) will be assessed. Patients meeting criteria for non-adherence (MPR<=60%) will be invited to participate in the trial. 336 non-adherent new statin users will undergo a fasting lipid panel, complete baseline questionnaires, and be randomly allocated to receive four sessions of adherence education delivered using MInt (EdMInt) or to an education control (EC) delivered at 3-month intervals. Final assessments will occur 12-months after the first EdMInt or EC session. The primary outcome is change in MPR adherence to statin medication from baseline to 12-months. Secondary outcomes include within-patient change in self-reported medication adherence, stage of change and self-efficacy for medication adherence, motivation to adhere to statin medication, and lipid profile. PMID- 27282120 TI - Corrigendum: Characterization of a temperature-responsive two component regulatory system from the Antarctic archaeon, Methanococcoides burtonii. PMID- 27282122 TI - Structural interconnections and the role of heptagonal rings in endohedral trimetallic nitride template fullerenes. AB - Recent experiments indicate that fullerene isomers outside the classical definition can also encapsulate metallic atoms or clusters to form endohedral metallofullerenes. Our systematic study using DFT calculations, suggests that many heptagon-including nonclassical trimetallic nitride template fullerenes are similar in stability to their classical counterparts, and that conversion between low-energy nonclassical and classical parent cages via Endo-Kroto insertion/extrusion of C2 units and Stone-Wales isomerization may facilitate the formation of endohedral trimetallic nitride fullerenes. Close structural connections are found between favored isomers of trimetallic nitride template fullerenes from C78 to C82 . It appears that the lower symmetry and local deformations associated with introduction of a heptagonal ring favor encapsulation of intrinsically less symmetrical mixed metal nitride clusters. (c) 2016 Wiley Periodicals, Inc. PMID- 27282121 TI - Activity-dependent plasticity of hippocampal place maps. AB - Hippocampal neurons encode a cognitive map of space. These maps are thought to be updated during learning and in response to changes in the environment through activity-dependent synaptic plasticity. Here we examine how changes in activity influence spatial coding in rats using halorhodopsin-mediated, spatially selective optogenetic silencing. Halorhoposin stimulation leads to light-induced suppression in many place cells and interneurons; some place cells increase their firing through disinhibition, whereas some show no effect. We find that place fields of the unaffected subpopulation remain stable. On the other hand, place fields of suppressed place cells were unstable, showing remapping across sessions before and after optogenetic inhibition. Disinhibited place cells had stable maps but sustained an elevated firing rate. These findings suggest that place representation in the hippocampus is constantly governed by activity-dependent processes, and that disinhibition may provide a mechanism for rate remapping. PMID- 27282123 TI - Nuclear magnetic resonance studies of DNP-ready trehalose obtained by solid state mechanochemical amorphization. AB - (1)H nuclear spin-lattice relaxation and Dynamic Nuclear Polarization (DNP) have been studied in amorphous samples of trehalose sugar doped with TEMPO radicals by means of mechanical milling, in the 1.6-4.2 K temperature range. The radical concentration was varied between 0.34 and 0.81%. The highest polarization of 15% at 1.6 K, observed in the sample with concentration 0.50%, is of the same order of magnitude of that reported in standard frozen solutions with TEMPO. The temperature and concentration dependence of the spin-lattice relaxation rate 1/T1, dominated by the coupling with the electron spins, were found to follow power laws with an exponent close to 3 in all samples. The observed proportionality between 1/T1 and the polarization rate 1/Tpol, with a coefficient related to the electron polarization, is consistent with the presence of Thermal Mixing (TM) and a good contact between the nuclear and the electron spins. At high electron concentration additional relaxation channels causing a decrease in the nuclear polarization must be considered. These results provide further support for a more extensive use of amorphous DNP-ready samples, obtained by means of comilling, in dissolution DNP experiments and possibly for in vivo metabolic imaging. PMID- 27282124 TI - Satiation meal and the effects of meal and body sizes on gastric evacuation rate in brook trout Salvelinus fontinalis fed commercial pellets. AB - Gastric evacuation (GE) experiments were performed on brook trout Salvelinus fontinalis fed commercial food pellets. The experiments included small fish (36 g; 15 cm total length, LT ) fed meals of 0.2, 0.4 and 0.8 g and large fish (152 g; 23 cm) fed meals of 0.8, 2.0 and 4.0 g at temperatures ranging from 15.1 to 18.2 degrees C. The stomach contents were thereafter sampled and weighed at 3 h intervals until the first empty stomach was observed. The course of GE was examined by use of a general power function of the data that revealed that the square-root function described the GE rate (GER) by the current stomach content mass independently of original meal size. Using the square-root function, the relationship between GER and fish size was described by a power function of fish length, whereas the effect of temperature was described by a simple exponential function. GER of the commercial pellets fed to S. fontinalis could thus be described by dStdt=-0.000464L1.31e0.052TSt (g h(-1) ), where St is stomach mass (g) at time t (h), L is total fish length (cm) and T is temperature ( degrees C). The result of this study should provide a useful tool for planning of feeding regimes in production of S. fontinalis by optimizing growth and minimizing food waste. PMID- 27282125 TI - Differences Between Psoriasis Patients and Skin-healthy Controls Concerning Appraisal of Touching, Shame and Disgust. AB - Psoriasis is a chronic skin disease associated with high levels of psychological distress and considerable life impact. Feelings of shame and stigmatization can lead to avoidance of social activity and intimacy. In this study, the questionnaire TSD-Q was used to evaluate pleasure in touching oneself and in a partnership, parental touching during childhood and (skin-related) shame and disgust. Skin-related disgust and shame were significantly higher in psoriatic patients than in healthy controls. Moreover, psoriasis-patients scored significantly lower than skin-healthy controls concerning appraisal of self touching and parental touching. In contrast, psoriasis-patients scored higher concerning appraisal of touching in a partnership. Due to the fact that low self esteem might enhance the negative evaluation of touch and the feelings of shame and disgust, psychological interventions should be integrated in the treatment of psoriasis. PMID- 27282126 TI - Multi-Walled Carbon Nanotubes as a Catalyst for Gas-Phase Oxidation of Ethanol to Acetaldehyde. AB - Multi-walled carbon nanotubes (CNTs) were directly used as a sustainable and green catalyst to convert ethanol into acetaldehyde in the presence of molecular oxygen. The C=O groups generated on the nanocarbon surface were demonstrated as active sites for the selective oxidation of ethanol to acetaldehyde. The transformation of disordered carbon debris on the CNT surface to ordered graphitic structures induced by thermal-treatment significantly enhanced the stability of the active C=O groups, and thus the catalytic performance. A high reactivity with approximately 60 % ethanol conversion and 93 % acetaldehyde selectivity was obtained over the optimized CNT catalyst at 270 degrees C. More importantly, the catalytic performance was quite stable even after 500 h, which is comparable with a supported gold catalyst. The robust catalytic performance displayed the potential application of CNTs in the industrial catalysis field. PMID- 27282127 TI - Generalizing the Concept of Specific Compound Formulation Additives towards Non Fluorescent Drugs: A Solubilization Study on Potential Anti-Alzheimer-Active Small-Molecule Compounds. AB - Tailor-made compound formulation additives enable the testing of potential drugs with undesirable pharmacological profiles. A combinatorial approach using Raman microscopy as the readout method is presented to select peptide sequences from large one-bead-one-compound libraries. The resulting peptide-PEG conjugates solubilize potential prophylactic and therapeutic anti-Alzheimer compounds and can be used as specific additives not only for fluorescent but also for non fluorescent compounds. PMID- 27282128 TI - Biodiversity and technological potential of lactic acid bacteria isolated from spontaneously fermented amaranth sourdough. AB - Spontaneous fermented sourdoughs prepared from amaranth flour were investigated for the presence of autochthonous lactic acid bacteria (LAB) predominating microbiota. The doughs were fermented with daily backslopping on a laboratory scale at 30 degrees C for 10 days. LAB counts ranged from 2.60 to 8.54 log CFU g( 1) with a pH declined from 6.2 to 3.8 throughout fermentation. The combined use of randomly amplified polymorphic DNA (RAPD)-PCR analysis and sequence analysis of 16S rRNA was applied for LAB intraspecies differentiation and taxonomic identification, respectively. Enterococcus, Pediococcus and Lactobacillus species were present in amaranth sourdoughs (AS). After the first refreshment step, Lactobacillus plantarum dominated AS until the end of fermentation. In coincidence, when DGGE analysis was performed, the occurrence of a progressive change in bacterial communities allowed the selection of Lact. plantarum as a dominant species. Moreover, technological, functional and safety characteristics of representative RAPD-biotypes were investigated. Lact. plantarum CRL1898 was selected as a potential candidate for gluten-free amaranth sourdough starter. SIGNIFICANCE AND IMPACT OF THE STUDY: Nowadays, there is an increasing interest in ancient noncereal gluten-free (GF) crops such as amaranth, due to their reported nutritional and health benefits. However, the use of these grains is still limited to traditional foods and bread making processes that are not yet well standardized. Results on the dynamics of autochthonous lactic acid bacteria (LAB) microbiota during laboratory spontaneous amaranth sourdoughs (AS) fermentation will contribute to overcome challenges for GF-fermented products development. In addition, knowledge about LAB diversity involving Enterococcus, Pediococcus and Lactobacillus species, with Lactobacillus plantarum predominating during AS fermentation, and their technological and functional properties provides the basis for the selection of autochthonous strains as starters cultures for novel gluten-free bakery products with enhanced nutritional, sensory and/or safety quality. PMID- 27282129 TI - Arginine side-chain modification that occurs during copper-catalysed azide-alkyne click reactions resembles an advanced glycation end product. AB - Dehydroascorbate is a by-product of copper-catalysed azide-alkyne click (CuAAC) reactions and also forms advanced glycation end products (AGEs) in tissues undergoing oxidative stress. Here we isolate and characterize an arginine dehydroascorbate adduct formed during CuAAC reactions, investigate strategies for preventing its formation, and propose its biological relevance as an AGE. PMID- 27282130 TI - The Camel Rhinarium: A Study Revealing the Presence of the Nasal Plane in Dromedary Camel (Camelus dromedarius), with Special Reference to Its Epidermal Structure. AB - The aim of this study was to prove that the nasal plane (Planum nasale) present in camel (Camelus dromedarius). Furthermore, it was the first description of the gross and primary microscopic anatomy as well as the epidermal ultrastructure of the camel nasal plane. Grossly, the camel rhinarium was formed of the glabrous grayish-black skin that extended to cover the philtrum and the medial nasal angles. It was composed of two perinasal parts and an inter-labial part. A shallow groove was passed across its middle. A dermatoglyphic pattern of epidermal ridges with primary and secondary fissures in between was revealed by scanning electron microscopy. The nasal plane was very small in relation to the camel head size. In general, the morphological appearance of the camel rhinarium was greatly similar to that of the proboscis-bearing mammals. The basic histological structure as well as the epidermal ultrastructure of the camel nasal plane was observed to resemble very closely the common type. Few differences were found, including indistinct or absent hypodermal layer, thinner stratum corneum and some basal cells have unusual sinuous bases. PMID- 27282131 TI - Signaled alternative reinforcement and the persistence of operant behavior. AB - Differential reinforcement of alternative behavior (DRA) is a treatment designed to eliminate problem behavior by reinforcing an alternative behavior at a higher rate. Availability of alternative reinforcement may be signaled, as with Functional Communication Training, or unsignaled. Whether or not alternative reinforcement is signaled could influence both the rate and persistence of problem behavior. The present study investigated whether signaling the availability of alternative reinforcement affects the rate and persistence of a concurrently available target response with pigeons. Three components of a multiple concurrent schedule arranged equal reinforcement rates for target responding. Two of the components also arranged equal reinforcement rates for an alternative response. In one DRA component, a discrete stimulus signaled the availability of response-contingent alternative reinforcement by changing the keylight color upon reinforcement availability. In the other DRA component, availability of alternative reinforcement was not signaled. Target responding was most persistent in the unsignaled DRA component when disrupted by satiation, free food presented between components, and extinction, relative to the signaled DRA and control components. These findings suggest the discrete stimulus functionally separated the availability of alternative reinforcement from the discriminative stimuli governing target responding. These findings provide a novel avenue to explore in translational research assessing whether signaling the availability of alternative reinforcement with DRA treatments reduces the persistence of problem behavior. PMID- 27282132 TI - High-resolution colonic motility recordings in vivo compared with ex vivo recordings after colectomy, in patients with slow transit constipation. AB - BACKGROUND: The pathogenesis of slow transit constipation (STC) remains poorly understood, with intrinsic and extrinsic abnormalities implicated. Here, we present high-resolution colonic manometry recordings from four STC patients recorded before total colectomy, and subsequently, ex vivo, after excision. METHODS: In four female, treatment-resistant STC patients (median age 35.5 years), a fiber-optic manometry catheter (72 sensors spaced at 1 cm intervals) was placed with the aid of a colonoscope, to the mid-transverse colon. Colonic manometry was recorded 2 h before and after a meal. After the colectomy, ex vivo colonic manometry was recorded in an organ bath. Ex vivo recordings were also made from colons from 4 patients (2 male; median age 67.5 years) undergoing anterior resection for nonobstructive carcinoma ('control' tissue). KEY RESULTS: A large increase in 'short single propagating contractions' was recorded in STC colon ex vivo compared to in vivo (ex vivo 61.3 +/- 32.7 vs in vivo 2.5 +/- 5/h). In STC patients, in vivo, the dominant frequency of contractile activity was 2-3 cycle per minute (cpm), whereas 1-cpm short-single propagating contractions dominated ex vivo. This same 1-cpm frequency was also dominant in control colons ex vivo. CONCLUSIONS & INFERENCES: In comparison to control adults, the colon of STC patients demonstrates significantly less propagating motor activity. However, once the STC colon is excised from the body it demonstrates a regular and similar frequency of propagating activity to control tissue. This paper provides interesting insights into the control of colonic motor patterns. PMID- 27282133 TI - Interaction between intra-oral cinnamaldehyde and nicotine assessed by psychophysical and physiological responses. AB - Cinnamaldehyde and nicotine activate the transient receptor potential subtype A1 (TRPA1) channel, which may cause burning sensations. This study investigated whether cinnamaldehyde modulates nicotine-induced psychophysical and physiological responses in oral tissues. Healthy non-smokers (n = 22) received, in a randomized, double-blind, crossover design, three different gums containing 4 mg of nicotine, 20 mg of cinnamaldehyde, or a combination thereof. Assessments of orofacial temperature and blood flow, blood pressure, heart rate, taste experience, and intra-oral pain/irritation area and intensity were performed before, during, and after a 10-min chewing regime. Cinnamaldehyde increased the temperature of the tongue and blood flow of the lip, and was associated with pain/irritation, especially in the mouth. Nicotine increased the temperature of the tongue and blood flow of the cheek, and produced pain/irritation in the mouth and throat. The combination of cinnamaldehyde and nicotine did not overtly change the psychophysical or physiological responses. Interestingly, half of the subjects responded to cinnamaldehyde as an irritant, and these cinnamaldehyde responders reported greater nicotine-induced pain/irritation areas in the throat. Whether sensitivity to cinnamaldehyde can predict the response to nicotine induced oral irritation remains to be determined. A better understanding of the sensory properties of nicotine in the oral mucosa has important therapeutic implications because pain and irritation represent compliance issues for nicotine replacement products. PMID- 27282134 TI - Peptide purification using the chemoselective reaction between N-(methoxy)glycine and isothiocyanato-functionalized resin. AB - An efficient peptide purification strategy is established, comprising the selective reaction of an N-terminal N-(methoxy)glycine residue of the peptide and isothiocyanato-functionalized resins, and subsequent Edman degradation. These reactions take place in acidic media; in particular, the Edman degradation proceeds smoothly in media containing more than 50% trifluoroacetic acid (v/v). These acidic conditions offer increased solubility, making them advantageous for the purification of hydrophobic and aggregation-prone peptides. The effectiveness of this method, together with scope and limitations, is demonstrated using model peptides and the practical purification of the loop region of the human dopamine D2 receptor long isoform (residues 240-272). Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27282135 TI - Peptide nanotube aligning side chains onto one side. AB - A novel pseudo cyclic penta-beta-peptide composed of a beta-naphthylalanine, two beta-alanines, and a sequence of ethylenediamine-succinic acid (CP5ES) is synthesized and investigated on peptide nanotube (PNT) formation. When the PNT is formed with the maximum number of intermolecular hydrogen bonds between the cyclic peptides, the sequence enables the alignment of the side chains, naphthyl groups, on one side of the PNT. Microscopic and spectroscopic observations of CP5ES crystals reveal that CP5ES forms rod- or needle-shaped molecular assemblies showing exciton coupling of the Cotton effect and predominant monomer emission, which are different from a reference cyclic tri-beta-peptide composed of a beta naphthylalanine and two beta-alanines. Insertion of a sequence of ethylenediamine succinic acid into beta-amino acids in the cyclic skeleton is therefore suggested to be effective to make the side chains aligning on one side of the PNT. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27282136 TI - Comparison of marmoset and human FSH using synthetic peptides of the beta-subunit L2 loop region and anti-peptide antibodies. AB - Follicle stimulating hormone (FSH) is a glycoprotein hormone required for female and male gametogenesis in vertebrates. Common marmoset (Callithrix jacchus) is a New World primate monkey, used as animal model in biomedical research. Observations like, requirement of extremely high dose of human FSH in marmosets for superovulation compared to other primates and generation of antibodies in marmoset against human FSH after repeated superovulation cycles, point towards the possibility that FSH-FSH receptor (FSHR) interaction in marmosets might be different than in the humans. In this study we attempted to understand some of these structural differences using FSH peptides and anti-peptide antibody approach. Based on sequence alignment, in silico modeling and docking studies, L2 loop of FSH beta-subunit (L2beta) was found to be different between marmoset and human. Hence, peptides corresponding to region 32-50 of marmoset and human L2beta loop were synthesized, purified and characterized. The peptides displayed dissimilarity in terms of molecular mass, predicted isoelectric point, predicted charge and in the ability to inhibit hormone-receptor interaction. Polyclonal antibodies generated against both the peptides were found to exhibit specific binding for the corresponding peptide and parent FSH in ELISA and Western blotting respectively and exhibited negligible reactivity to cross-species peptide and FSH in ELISA. The anti-peptide antibody against marmoset FSH was also able to detect native FSH in marmoset plasma samples and pituitary sections. In summary, the L2beta loop of marmoset and human FSH has distinct receptor interaction ability and immunoreactivity indicating possibility of subtle conformational and biochemical differences between the two regions which may affect the FSH-FSHR interaction in these two primates. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27282137 TI - Beta amino acid-modified and fluorescently labelled kisspeptin analogues with potent KISS1R activity. AB - Kisspeptin analogues with improved metabolic stability may represent important ligands in the study of the kisspeptin/KISS1R system and have therapeutic potential. In this paper we assess the activity of known and novel kisspeptin analogues utilising a dual luciferase reporter assay in KISS1R-transfected HEK293T cells. In general terms the results reflect the outcomes of other assay formats and a number of potent agonists were identified among the analogues, including beta(2) -hTyr-modified and fluorescently labelled forms. We also showed, by assaying kisspeptin in the presence of protease inhibitors, that proteolysis of kisspeptin activity within the reporter assay itself may diminish the agonist outputs. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27282139 TI - Retraction statement: 'S14G-humanin inhibits Abeta1-42 fibril formation, disaggregates preformed fibrils, and protects against Abeta-induced cytotoxicity in vitro' by Wei Zhang, Ying Du, Miao Bai, Ye Xi, Zhuyi Li and Jianting Miao J. Peptide Sci. 2013; 19: 159-165. DOI:10.1002/psc.2484. PMID- 27282138 TI - Site-specific conjugation of the quencher on peptide's N-terminal for the synthesis of a targeted non-spreading activatable optical probe. AB - Optical imaging offers high sensitivity and portability at low cost. The design of 'smart' or 'activatable' probes can decrease the background noise and increase the specificity of the signal. By conjugating a fluorescent dye and a compatible quencher on each side of an enzyme's substrate, the signal remains in its 'off ' state until it reaches the area where a specific enzyme is expressed. However, the signal can leak from that area unless the dye is attached to a molecule able to bind to a specific target also presented in that area. The aim of this study was to (i) specifically conjugate the quencher on the alpha-amino group of the peptide's N-terminus, (ii) conjugate the dye on the epsilon-amino group of a lysine in C-terminus, and (iii) conjugate the carboxyl group of the peptide's C terminus to an amino group present on an antibody, using carbodiimide chemistry. The use of protecting groups, such as Boc or Fmoc, to allow site-specific conjugation, presents several drawbacks including 'on beads labeling', additional steps required for deprotection and removal from the resin, decreased yield, and dye degradation. A method of preferential labeling of alpha-amino N-terminal group in slightly acidic solution, proposed by Selo et al. (1996) has partially solved the problem. The present study reports improvements of the method allowing to (i) avoid the homo-bilabeling, (ii) increase the yield of the N-terminal labeling by two folds, and (iii) decrease the cost by 44-fold. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd. PMID- 27282140 TI - Decadal variability in the occurrence of wintertime haze in central eastern China tied to the Pacific Decadal Oscillation. AB - Haze is a serious issue in China with increasing concerns, and understanding the factors driving decadal-scale variations in haze occurrence is relevant for government policymaking. Using a comprehensive observational haze dataset, we demonstrate notable decadal fluctuations in the number of haze days (HD) during winter in central eastern China, showing a decline since the mid-1980s. The leading mode of the wintertime HD features an increasing trend for 1959-2012 in eastern China, highly correlated with China's gross domestic product (GDP) that represents increasing trend of pollutant emissions, and to a lesser extent meteorological factors. The second mode shows decadal variations in central eastern China associated with Pacific Decadal Oscillation (PDO). Observations and numerical simulations suggest that Mongolia High and corresponding descending motion tend to be enhanced (weakened) in central eastern China during the positive (negative) phase of PDO. With PDO shifting towards a negative phase, the weakened Mongolia High and ascending anomalies make the air unstable and conduce to the spread of pollutants, leading to the decline in the wintertime HD over central eastern China since the mid-1980s. Based on above physical mechanisms, a linear model based on PDO and GDP metrics provided a good fit to the observed HD. PMID- 27282141 TI - Immunological biomarkers associated with brain structure and executive function in late-life depression: exploratory pilot study. AB - OBJECTIVE: Several immunological biomarkers are altered in late-life major depressive disorder (LLD). Immunological alterations could contribute to LLD's consequences, but little is known about the relations between specific immunological biomarkers and brain health in LLD. We performed an exploratory pilot study to identify, from several candidates, the specific immunological biomarkers related to important aspects of brain health that are altered in LLD (brain structure and executive function). METHODS: Adults (n = 31) were at least 60 years old and had major depressive disorder. A multiplex immunoassay assessed 13 immunological biomarkers, and we examined their associations with structural MRI (grey matter volume and white matter hyperintensity volume (WMH)) and executive function (Color-Word Interference and Trail-Making tests) measures. RESULTS: Vascular endothelial growth factor (VEGF) and the chemokine eotaxin had significant negative associations with grey matter volume (VEGF: n = 31, r = 0.65; eotaxin: n = 29, r = -0.44). Tumor necrosis factor alpha (TNF-alpha) had a significant positive relationship with WMHs (n = 30, r = 0.52); interferon-gamma (IFN-gamma) and macrophage inflammatory protein-1alpha (MIP-1alpha) were also significantly associated with WMHs (IFN-gamma: n = 31, r = 0.48; MIP-1alpha: n = 29, r = 0.45). Only eotaxin was associated with executive function (set-shifting performance as measured with the Trail-making test: n = 33, r = -0.43). CONCLUSIONS: Immunological markers are associated with brain structure in LLD. We found the immunological correlates of grey and white matter differ. Prospective studies are needed to evaluate whether these immunological correlates of brain health increase the risk of LLD's consequences. Eotaxin, which correlated with both grey matter volume and set-shifting performance, may be particularly relevant to neurodegeneration and cognition in LLD. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27282142 TI - Seedling growth responses to phosphorus reflect adult distribution patterns of tropical trees. AB - Soils influence tropical forest composition at regional scales. In Panama, data on tree communities and underlying soils indicate that species frequently show distributional associations to soil phosphorus. To understand how these associations arise, we combined a pot experiment to measure seedling responses of 15 pioneer species to phosphorus addition with an analysis of the phylogenetic structure of phosphorus associations of the entire tree community. Growth responses of pioneers to phosphorus addition revealed a clear tradeoff: species from high-phosphorus sites grew fastest in the phosphorus-addition treatment, while species from low-phosphorus sites grew fastest in the low-phosphorus treatment. Traits associated with growth performance remain unclear: biomass allocation, phosphatase activity and phosphorus-use efficiency did not correlate with phosphorus associations; however, phosphatase activity was most strongly down-regulated in response to phosphorus addition in species from high-phosphorus sites. Phylogenetic analysis indicated that pioneers occur more frequently in clades where phosphorus associations are overdispersed as compared with the overall tree community, suggesting that selection on phosphorus acquisition and use may be strongest for pioneer species with high phosphorus demand. Our results show that phosphorus-dependent growth rates provide an additional explanation for the regional distribution of tree species in Panama, and possibly elsewhere. PMID- 27282143 TI - Quantitative phosphoproteomic analysis of the PI3K-regulated signaling network. AB - The PI3K pathway is commonly activated in cancer. Only a few studies have attempted to explore the spectrum of phosphorylation signaling downstream of the PI3K cascade. Such insight, however, is imperative to understand the mechanisms responsible for oncogenic phenotypes. By applying MS-based phosphoproteomics, we mapped 2509 phosphorylation sites on 1096 proteins, and quantified their responses to activation or inhibition of PIK3CA using isogenic knock-in derivatives and a series of targeted inhibitors. We uncovered phosphorylation changes in a wide variety of proteins involved in cell growth and proliferation, many of which have not been previously associated with PI3K signaling. A significant update of the posttranslational modification database PHOSIDA (http://www.phosida.com) allows efficient use of the data. All MS data have been deposited in the ProteomeXchange with identifier PXD003899 (http://proteomecentral.proteomexchange.org/dataset/PXD003899). PMID- 27282144 TI - The Psychosomatic Practice. AB - There is increasing awareness of the limitations of the disease oriented approach in medical care. The primary goal of psychosomatic medicine is to correct this inadequacy by incorporation of innovative operational strategies into clinical practice. Psychosomatic practice can be recognized by 2 distinctive features: the holistic approach to patient management (encompassing psychosocial factors) and the clinical model of reasoning (which reflects a multifactorial frame of reference). A basic psychosomatic assumption is the consideration of patients as partners in managing disease. The partnership paradigm includes collaborative care (a patient-physician relationship in which physicians and patients make health decisions together) and implementation of self-management (a plan that provides patients with problem-solving skills to enhance their self-efficacy). Pointing to strategies that focus on individual needs may improve patient quality of life and final outcomes. PMID- 27282145 TI - Genome-wide detection of CNVs in Chinese indigenous sheep with different types of tails using ovine high-density 600K SNP arrays. AB - Chinese indigenous sheep can be classified into three types based on tail morphology: fat-tailed, fat-rumped, and thin-tailed sheep, of which the typical breeds are large-tailed Han sheep, Altay sheep, and Tibetan sheep, respectively. To unravel the genetic mechanisms underlying the phenotypic differences among Chinese indigenous sheep with tails of three different types, we used ovine high density 600K SNP arrays to detect genome-wide copy number variation (CNV). In large-tailed Han sheep, Altay sheep, and Tibetan sheep, 371, 301, and 66 CNV regions (CNVRs) with lengths of 71.35 Mb, 51.65 Mb, and 10.56 Mb, respectively, were identified on autosomal chromosomes. Ten CNVRs were randomly chosen for confirmation, of which eight were successfully validated. The detected CNVRs harboured 3130 genes, including genes associated with fat deposition, such as PPARA, RXRA, KLF11, ADD1, FASN, PPP1CA, PDGFA, and PEX6. Moreover, multilevel bioinformatics analyses of the detected candidate genes were significantly enriched for involvement in fat deposition, GTPase regulator, and peptide receptor activities. This is the first high-resolution sheep CNV map for Chinese indigenous sheep breeds with three types of tails. Our results provide valuable information that will support investigations of genomic structural variation underlying traits of interest in sheep. PMID- 27282147 TI - Synthesis, Structure, Optical, and Electrochemical Properties of Triple- and Quadruple-Decker Co-facial Tetrathiafulvalene Arrays. AB - Understanding the details of the electronic structure in face-to-face arranged tetrathiafulvalenes (TTFs) is very important for the design of supramolecular functional materials and superior conductive organic materials. This article is a comprehensive study of the interactions among columnar stacked TTFs using trimeric (trimer) and tetrameric (tetramer) TTFs linked by alkylenedithio groups (-S(CH2 )n S-, n=1-4) as models of triple- and quadruple-decker TTF arrays. Single-crystal X-ray analyses of neutral trimeric TTFs revealed that the three TTF moieties are oriented in a zigzag arrangement. Cyclic voltammetry measurements (CV) reveal that the trimer and tetramer exhibited diverse reversible redox processes with multi-electron transfers, depending on the length of the -S(CH2 )n S- units and substituents. The electronic spectra of the radical cations, prepared by electrochemical oxidation, showed charge resonance (CR) bands in the NIR/IR region (1630-1850 nm), attributed to a mixed valence (MV) state of the triple- and quadruple-decker TTF arrays. In the trimeric systems, the dicationic state (+2; 0.66 cation per TTF unit) was found to be a stable state, whereas the monocationic state (+1) was not observed in the electronic spectra. In the tetrameric system, substituent-dependent redox processes were observed. Moreover, pi-trimers and pi-tetramers, which show a significant Davydov blueshift in the spectra, are formed in the tricationic (trimer) and tetracationic (tetramer) state. In addition, these attractive interactions are strongly dependent on the length of the linkage unit. PMID- 27282148 TI - Malaria: Global progress 2000 - 2015 and future challenges. AB - BACKGROUND: 2015 was the target year for malaria goals set by the World Health Assembly and other international institutions to reduce malaria incidence and mortality. A review of progress indicates that malaria programme financing and coverage have been transformed since the beginning of the millennium, and have contributed to substantial reductions in the burden of disease. FINDINGS: Investments in malaria programmes increased by more than 2.5 times between 2005 and 2014 from US$ 960 million to US$ 2.5 billion, allowing an expansion in malaria prevention, diagnostic testing and treatment programmes. In 2015 more than half of the population of sub-Saharan Africa slept under insecticide-treated mosquito nets, compared to just 2 % in 2000. Increased availability of rapid diagnostic tests and antimalarial medicines has allowed many more people to access timely and appropriate treatment. Malaria incidence rates have decreased by 37 % globally and mortality rates by 60 % since 2000. It is estimated that 70 % of the reductions in numbers of cases in sub-Saharan Africa can be attributed to malaria interventions. CONCLUSIONS: Reductions in malaria incidence and mortality rates have been made in every WHO region and almost every country. However, decreases in malaria case incidence and mortality rates were slowest in countries that had the largest numbers of malaria cases and deaths in 2000; reductions in incidence need to be greatly accelerated in these countries to achieve future malaria targets. Progress is made challenging because malaria is concentrated in countries and areas with the least resourced health systems and the least ability to pay for system improvements. Malaria interventions are nevertheless highly cost-effective and have not only led to significant reductions in the incidence of the disease but are estimated to have saved about US$ 900 million in malaria case management costs to public providers in sub Saharan Africa between 2000 and 2014. Investments in malaria programmes can not only reduce malaria morbidity and mortality, thereby contributing to the health targets of the Sustainable Development Goals, but they can also transform the well-being and livelihood of some of the poorest communities across the globe. PMID- 27282146 TI - Prospects for HIV control in South Africa: a model-based analysis. AB - BACKGROUND: The goal of virtual elimination of horizontal and mother-to-child HIV transmission in South Africa (SA) has been proposed, but there have been few systematic investigations of which interventions are likely to be most critical to reducing HIV incidence. OBJECTIVE: This study aims to evaluate SA's potential to achieve virtual elimination targets and to identify which interventions will be most critical to achieving HIV incidence reductions. DESIGN: A mathematical model was developed to simulate the population-level impact of different HIV interventions in SA. Probability distributions were specified to represent uncertainty around 32 epidemiological parameters that could be influenced by interventions, and correlation coefficients (r) were calculated to assess the sensitivity of the adult HIV incidence rates and mother-to-child transmission rates (2015-2035) to each epidemiological parameter. RESULTS: HIV incidence in SA adults (ages 15-49) is expected to decline from 1.4% in 2011-2012 to 0.29% by 2035 (95% CI: 0.10-0.62%). The parameters most strongly correlated with future adult HIV incidence are the rate of viral suppression after initiating antiretroviral treatment (ART) (r=-0.56), the level of condom use in non-marital relationships (r=-0.40), the phase-in of intensified risk-reduction counselling for HIV-positive adults (r=0.29), the uptake of medical male circumcision (r= 0.24) and the phase-in of universal ART eligibility (r=0.22). The paediatric HIV parameters most strongly associated with mother-to-child transmission rates are the relative risk of transmission through breastfeeding when the mother is receiving ART (r=0.70) and the rate of ART initiation during pregnancy (r=-0.16). CONCLUSIONS: The virtual elimination target of a 0.1% incidence rate in adults will be difficult to achieve. Interventions that address the infectiousness of patients after ART initiation will be particularly critical to achieving long term HIV incidence declines in South Africa. PMID- 27282149 TI - Primary mucinous carcinoma with rhabdoid cells of the thyroid gland: a case report. AB - BACKGROUND: Primary mucinous carcinoma of the thyroid gland is a rare disease; only 6 cases of primary mucinous carcinoma of the thyroid have been previously reported. Primary mucinous carcinoma of the thyroid gland with incomplete tumor resection tends to be associated with a poor prognosis, resulting in death within a few months. An early and appropriate diagnosis may contribute to improvement in patient prognosis; however, it is extremely difficult to diagnose primary mucinous carcinoma of the thyroid. We present the seventh reported case of primary mucinous carcinoma in the thyroid gland; moreover, rhabdoid cells were detected, which, to our knowledge, is a novel finding. CASE PRESENTATION: An 81 year-old Japanese woman was initially diagnosed with a poorly differentiated thyroid carcinoma, and she underwent a hemithyroidectomy. Pathological examination revealed the presence of abundant mucus and agglomeration of large atypical cells. Rhabdoid cells were also seen scattered among the tumor cells. Immunostaining was performed for various markers, and on the basis of these results, we diagnosed the lesion as primary mucinous carcinoma with rhabdoid cells in the thyroid gland. Ten months after surgery, recurrence was noted in the paratracheal lymph nodes; therefore, total resection of the residual thyroid gland and paratracheal lymphadenectomy with thyroid-stimulating hormone suppression were performed. The patient is currently alive and disease-free. CONCLUSIONS: The current case is of interest not only because of the rare histological findings, but also because the patient achieved long-term survival following diagnosis of a mucinous carcinoma. We believe this report will be helpful for diagnosing future cases of mucinous carcinoma of the thyroid. PMID- 27282150 TI - Study design and data analysis considerations for the discovery of prognostic molecular biomarkers: a case study of progression free survival in advanced serous ovarian cancer. AB - BACKGROUND: Accurate discovery of molecular biomarkers that are prognostic of a clinical outcome is an important yet challenging task, partly due to the combination of the typically weak genomic signal for a clinical outcome and the frequently strong noise due to microarray handling effects. Effective strategies to resolve this challenge are in dire need. METHODS: We set out to assess the use of careful study design and data normalization for the discovery of prognostic molecular biomarkers. Taking progression free survival in advanced serous ovarian cancer as an example, we conducted empirical analysis on two sets of microRNA arrays for the same set of tumor samples: arrays in one set were collected using careful study design (that is, uniform handling and randomized array-to-sample assignment) and arrays in the other set were not. RESULTS: We found that (1) handling effects can confound the clinical outcome under study as a result of chance even with randomization, (2) the level of confounding handling effects can be reduced by data normalization, and (3) good study design cannot be replaced by post-hoc normalization. In addition, we provided a practical approach to define positive and negative control markers for detecting handling effects and assessing the performance of a normalization method. CONCLUSIONS: Our work showcased the difficulty of finding prognostic biomarkers for a clinical outcome of weak genomic signals, illustrated the benefits of careful study design and data normalization, and provided a practical approach to identify handling effects and select a beneficial normalization method. Our work calls for careful study design and data analysis for the discovery of robust and translatable molecular biomarkers. PMID- 27282151 TI - MALDI-TOF mass spectrometry as a potential tool for Trichomonas vaginalis identification. AB - BACKGROUND: Trichomonas vaginalis is a flagellated protozoan causing trichomoniasis, a sexually transmitted human infection, with around 276.4 million new cases estimated by World Health Organization. Culture is the gold standard method for the diagnosis of T. vaginalis infection. Recently, immunochromatographic assays as well as PCR assays for the detection of T. vaginalis antigen or DNA, respectively, have been also available. Although the well-known genome sequence of T. vaginalis has made possible the application of proteomic studies, few data are available about the overall proteomic expression profiling of T. vaginalis. The aim of this study was to investigate the potential application of MALDI-TOF MS as a new tool for the identification of T. vaginalis. METHODS: Twenty-one isolates were analysed by MALDI-TOF MS after the creation of a Main Spectrum Profile (MSP) from a T. vaginalis reference strain (G3) and its subsequent supplementation in the Bruker Daltonics database, not including any profile of protozoa. This was achieved after the development of a new identification method created by modifying the range setting (6-10 kDa) for the MALDI-TOF MS analysis in order to exclude the overlapping of peaks derived from the culture media used in this study. RESULTS: Two MSP reference spectra were created in 2 different range: 3-15 kDa (standard range setting) and 6-10 kDa (new range setting). Both MSP spectra were deposited in the MALDI BioTyper database for further identification of additional T. vaginalis strains. All the 21 strains analysed in this study were correctly identified by using the new identification method. CONCLUSIONS: In this study it was demonstrated that changes in the MALDI TOF MS standard parameters usually used to identify bacteria and fungi allowed the identification of the protozoan T. vaginalis. This study shows the usefulness of MALDI-TOF MS in the reliable identification of microorganism grown on complex liquid media such as the protozoan T. vaginalis, on the basis of the proteic profile and not on the basis of single markers, by using a "new range setting" different from that developed for bacteria and fungi. PMID- 27282152 TI - Susceptibility to antifungal agents and enzymatic activity of Candida haemulonii and Cutaneotrichosporon dermatis isolated from soft corals on the Brazilian reefs. AB - Candida is a common fungus with the capacity to cause infections in humans. However, most studies have concentrated on clinical isolates and little is known about the identity, ecology and drug resistance of free living species/strains. Here, we isolate eight strains of Candida haemulonii and four strains of Cutaneotrichosporon dermatis from three marine cnidarian zoanthids species (Palythoa caribaeorum, Palythoa variabilis and Zoanthus sociatus) collected from Brazilian coral reefs. Strains were identified by sequencing of the D1/D2 domain LSU rDNA and ITS region. We tested these environmental isolates for their capacity to grow in media with increasing concentration of NaCl, capacity to grow in different temperatures, enzymatic activity and antifungal susceptibility. For C. haemulonii, all strains strongly produced gelatinase, esterase and albuminase and were either able to express lipase, phospholipase and keratinase, but not express urease and DNase. The strains were able to grow at 37 degrees C, but not at 39 degrees C, and except for LMS 40, all of them could grow in a 10 % NaCl medium. All isolates were resistant to all antifungals tested, with exception for ketoconazole and tioconazole (MIC = 2 ug/mL). For C. dermatis, all strains could grow at 39 degrees C and could not express phospholipase, keratinase or gelatinase. However, all were capable of expressing urease, lipase and esterase. Three out of four strains could grow in a 10 % NaCl medium, but none grew in a 30 % NaCl medium. The strains showed high values of minimal inhibitory concentration. LMPV 90 was resistant to tioconazole, terbinafine, fluconazole and posaconazole, and LMS 38 was resistant to all antifungal agents tested. We discuss the characterization of C. haemulonii and C. dermatis as a possible emerging pathogen due to its animal-related enzymatic arsenal and antifungal resistance. PMID- 27282154 TI - The Crossed Projection to the Striatum in Two Species of Monkey and in Humans: Behavioral and Evolutionary Significance. AB - The corpus callosum establishes the anatomical continuity between the 2 hemispheres and coordinates their activity. Using histological tracing, single axon reconstructions, and diffusion tractography, we describe a callosal projection to n caudatus and putamen in monkeys and humans. In both species, the origin of this projection is more restricted than that of the ipsilateral projection. In monkeys, it consists of thin axons (0.4-0.6 um), appropriate for spatial and temporal dispersion of subliminal inputs. For prefrontal cortex, contralateral minus ipsilateral delays to striatum calculated from axon diameters and conduction distance are <2 ms in the monkey and, by extrapolation, <4 ms in humans. This delay corresponds to the performance in Poffenberger's paradigm, a classical attempt to estimate central conduction delays, with a neuropsychological task. In both species, callosal cortico-striatal projections originate from prefrontal, premotor, and motor areas. In humans, we discovered a new projection originating from superior parietal lobule, supramarginal, and superior temporal gyrus, regions engaged in language processing. This projection crosses in the isthmus the lesion of which was reported to dissociate syntax and prosody. The projection might originate from an overproduction of callosal projections in development, differentially pruned depending on species. PMID- 27282153 TI - A novel anticancer agent icaritin inhibited proinflammatory cytokines in TRAMP mice. AB - PURPOSE: We aimed to investigate whether icaritin (ICT) would inhibit serum proinflammatory cytokines and postpone prostate cancer (PCa) development and progression in both normal diet and high-fat diet (HFD) transgenic adenocarcinoma mouse prostate (TRAMP) mice. METHODS: TRAMP mice were randomly divided into four groups: normal diet with/without ICT group and HFD with/without ICT group. Each TRAMP mouse received intraperitoneal injection of ICT solution at the dose of 30 mg/kg 5 times per week. RESULTS: ICT treatment could significantly increase the survival when compared with those in normal diet group (P = 0.015, log-rank test) and HFD group (P = 0.009, log-rank test). Proinflammatory cytokine levels, including IL-1alpha, IL-1beta, IL-6, and TNF-alpha, were decreased more or less in ICT-treated TRAMP mice. Moreover, significant higher inflammation scores were detected in normal diet group and HFD group compared with their relevant ICT treatment groups (P = 0.026 and P = 0.006, respectively). Meanwhile, the incidences of well-differentiated tumor tissue in two ICT treatment groups (39.13 and 31.82 %) were moderately higher than control groups (29.41 and 20.00 %, respectively), though no significant difference was observed. CONCLUSIONS: Taken together, our findings indicate that ICT could inhibit the development and progression of PCa in TRAMP mice via inhibiting proinflammatory cytokines. PMID- 27282155 TI - Synthesis and evaluation of selected 1,3,4-oxadiazole derivatives for in vitro cytotoxicity and in vivo anti-tumor activity. AB - The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V 79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight. PMID- 27282156 TI - A new class of fatty acid allene oxide formed by the DOX-P450 fusion proteins of human and plant pathogenic fungi, C. immitis and Z. tritici. AB - Linoleate dioxygenase-cytochrome P450 (DOX-CYP) fusion enzymes are common in pathogenic fungi. The DOX domains form hydroperoxy metabolites of 18:2n-6, which can be transformed by the CYP domains to 1,2- or 1,4-diols, epoxy alcohols, or to allene oxides. We have characterized two novel allene oxide synthases (AOSs), namely, recombinant 8R-DOX-AOS of Coccidioides immitis (causing valley fever) and 8S-DOX-AOS of Zymoseptoria tritici (causing septoria tritici blotch of wheat). The 8R-DOX-AOS oxidized 18:2n-6 sequentially to 8R-hydroperoxy-9Z,12Z octadecadienoic acid (8R-HPODE) and to an allene oxide, 8R(9)-epoxy-9,12Z octadecadienoic acid, as judged from the accumulation of the alpha-ketol, 8S hydroxy-9-oxo-12Z-octadecenoic acid. The 8S-DOX-AOS of Z. tritici transformed 18:2n-6 sequentially to 8S-HPODE and to an alpha-ketol, 8R-hydroxy-9-oxo-12Z octadecenoic acid, likely formed by hydrolysis of 8S(9)-epoxy-9,12Z octadecadienoic acid. The 8S-DOX-AOS oxidized [8R-(2)H]18:2n-6 to 8S-HPODE with retention of the (2)H-label, suggesting suprafacial hydrogen abstraction and oxygenation in contrast to 8R-DOX-AOS. Both enzymes oxidized 18:1n-9 and 18:3n-3 to alpha-ketols, but the catalysis of the 8R- and 8S-AOS domains differed. 8R-DOX AOS transformed 9R-HPODE to epoxy alcohols, but 8S-DOX-AOS converted 9S-HPODE to an alpha-ketol (9-hydroxy-10-oxo-12Z-octadecenoic acid) and epoxy alcohols in a ratio of ~1:2. Whereas all fatty acid allene oxides described so far have a conjugated diene impinging on the epoxide, the allene oxides formed by 8-DOX-AOS are unconjugated. PMID- 27282157 TI - Interactions of mucins with the Tn or Sialyl Tn cancer antigens including MUC1 are due to GalNAc-GalNAc interactions. AB - The molecular mechanism(s) underlying the enhanced self-interactions of mucins possessing the Tn (GalNAcalpha1-Ser/Thr) or STn (NeuNAcalpha2-6GalNAcalpha1 Ser/Thr) cancer markers were investigated using optical tweezers (OT). The mucins examined included modified porcine submaxillary mucin containing the Tn epitope (Tn-PSM), ovine submaxillary mucin with the STn epitope (STn-OSM), and recombinant MUC1 analogs with either the Tn and STn epitope. OT experiments in which the mucins were immobilized onto polystyrene beads revealed identical self interaction characteristics for all mucins. Identical binding strength and energy landscape characteristics were also observed for synthetic polymers displaying multiple GalNAc decorations. Polystyrene beads without immobilized mucins showed no self-interactions and also no interactions with mucin-decorated polystyrene beads. Taken together, the experimental data suggest that in these molecules, the GalNAc residue mediates interactions independent of the anchoring polymer backbone. Furthermore, GalNAc-GalNAc interactions appear to be responsible for self-interactions of mucins decorated with the STn epitope. Hence, Tn-MUC1 and STn-MUC1 undergo self-interactions mediated by the GalNAc residue in both epitopes, suggesting a possible molecular role in cancer. MUC1 possessing the T (Galbeta1-3GalNAcalpha1-Ser/Thr) or ST antigen (NeuNAcalpha2-3Galbeta1 3GalNAcalpha1-Ser/Thr) failed to show self-interactions. However, in the case of ST-MUC1, self-interactions were observed after subsequent treatment with neuraminidase and beta-galactosidase. This enzymatic treatment is expected to introduce Tn-epitopes and these observations thus further strengthen the conclusion that the observed interactions are mediated by the GalNAc groups. PMID- 27282158 TI - Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus. AB - BACKGROUND: The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. METHODS: Subjects (18-64 years; body mass index 20.0-28.0 kg/m2; glycated hemoglobin <=9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. RESULTS: The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. CONCLUSIONS: Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665. PMID- 27282159 TI - Clinical Pharmacokinetics and Pharmacodynamics of Saxagliptin, a Dipeptidyl Peptidase-4 Inhibitor. AB - Saxagliptin is an orally active, highly potent, selective and competitive dipeptidyl peptidase (DPP)-4 inhibitor used in the treatment of type 2 diabetes mellitus at doses of 2.5 or 5 mg once daily. DPP-4 is responsible for degrading the intestinally derived hormones glucagon-like peptide (GLP)-1 and glucose dependent insulinotropic polypeptide (GIP). Inhibition of DPP-4 increases intact plasma GLP-1 and GIP concentrations, augmenting glucose-dependent insulin secretion. Both saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, demonstrate high degrees of selectivity for DPP-4 compared with other DPP enzymes. Saxagliptin is orally absorbed and can be administered with or without food. The half-life of plasma DPP-4 inhibition with saxagliptin 5 mg is ~27 h, which supports a once-daily dosing regimen. Saxagliptin is metabolized by cytochrome P450 (CYP) 3A4/5 and is eliminated by a combination of renal and hepatic clearance. No clinically meaningful differences in saxagliptin or 5 hydroxy saxagliptin pharmacokinetics have been detected in patients with hepatic impairment. No clinically meaningful differences in saxagliptin or 5-hydroxy saxagliptin pharmacokinetics have been detected in patients with mild renal impairment, whereas dose reduction is recommended in patients with moderate or severe renal impairment because of greater systemic exposure [the area under the plasma concentration-time curve (AUC)] to saxagliptin total active moieties. Clinically relevant drug-drug interactions have not been detected; however, limiting the dose to 2.5 mg once daily is recommended in the USA when saxagliptin is coadministered with strong CYP inhibitors, because of increased saxagliptin exposure. In summary, saxagliptin has a predictable pharmacokinetic and pharmacodynamic profile. PMID- 27282160 TI - GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features. AB - Vitamin D deficiency is suggested to be associated with Parkinson's disease (PD). Our aim was to investigate the serum 25-hydroxyvitamin D3 (25OHD) levels of PD patients in Turkish cohort, to investigate any association of vitamin D binding protein (GC) genotypes with PD due to the significant role of GC in vitamin D transport, to determine whether vitamin D receptor (VDR) haplotype that we previously demonstrated to be a risk haplotype for AD is also a common haplotype for PD and to investigate any relevant consequence of serum 25OHD levels, GC or VDR genotypes on clinical features of PD. Three hundred eighty-two PD patients and 242 healthy subjects were included in this study. The serum 25OHD levels were investigated by CLIA, and GC and VDR SNPs were evaluated with LightSnip. Our results indicated a strong relationship between low serum 25OHD levels and PD (p < 0.001). rs7041 of GC and ApaI of VDR were associated with the PD risk (p < 0.05). Minor allele carriers for BsmI of VDR gene in both PD patients and healthy subjects had significantly higher levels of serum 25OHD (p < 0.05). The homozygous major allele carriers for rs2282679, rs3755967 and rs2298850 of GC gene in PD patients with slower progression had significantly higher levels of serum 25OHD (p < 0.05). Minor allele carriers for FokI of VDR gene were more frequent in patients with advanced-stage PD (p < 0.05). Consequently, this is the first study demonstrating GC gene as a risk factor for PD. The relationship between PD's clinical features and low 25OHD or risk genotypes might have effects on PD independently. PMID- 27282161 TI - Assessment of edema volume in skin upon injury in a mouse ear model with optical coherence tomography. AB - Accurate measurement of edema volume is essential for the investigation of tissue response and recovery following a traumatic injury. The measurements must be noninvasive and repetitive over time so as to monitor tissue response throughout the healing process. Such techniques are particularly necessary for the evaluation of therapeutics that are currently in development to suppress or prevent edema formation. In this study, we propose to use optical coherence tomography (OCT) technique to image and quantify edema in a mouse ear model where the injury is induced by a superficial-thickness burn. Extraction of edema volume is achieved by an attenuation compensation algorithm performed on the three dimensional OCT images, followed by two segmentation procedures. In addition to edema volume, the segmentation method also enables accurate thickness mapping of edematous tissue, which is an important characteristic of the external symptoms of edema. To the best of our knowledge, this is the first method for noninvasively measuring absolute edema volume. PMID- 27282162 TI - Detection of interventricular dyssynchrony: An evolution of the phase analysis technique. PMID- 27282163 TI - Can project management principles help the sports clinician manage return to play? PMID- 27282164 TI - Early identification of autism spectrum disorder: Do we need a paradigm shift? PMID- 27282165 TI - Anodic concentration loss and impedance characteristics in rotating disk electrode microbial fuel cells. AB - A rotating disk electrode (RDE) was used to investigate the concentration loss and impedance characteristics of anodic biofilms in microbial fuel cells (MFCs). Amperometric time-current analysis revealed that at the rotation rate of 480 rpm, a maximum current density of 168 uA cm(-2) can be achieved, which was 22.2 % higher than when there was no rotation. Linear sweep voltammetry and electrochemical impedance spectroscopy tests showed that when the anodic potential was set to -300 mV vs. Ag/AgCl reference, the power densities could increase by 59.0 %, reaching 1385 mW m(-2), the anodic resistance could reduce by 19 %, and the anodic capacitance could increase by 36 %. These results concur with a more than 85 % decrease of the diffusion layer thickness. Data indicated that concentration loss, diffusion layer thickness, and the mixing velocity play important roles in anodic resistance reduction and power output of MFCs. These findings could be helpful to the design of future industrial-scale MFCs with mixed bacteria biofilms. PMID- 27282166 TI - A newly isolated and identified vitamin B12 producing strain: Sinorhizobium meliloti 320. AB - Vitamin B12 (Cobalamin, VB12) has several physiological functions and is widely used in pharmaceutical and food industries. A new unicellular species was extracted from China farmland, and the strain could produce VB12 which was identified by HPLC and HPLC-MS/MS. 16S rDNA analysis reveals this strain belongs to the species Sinorhizobium meliloti and we named it S. meliloti 320. Its whole genome information indicates that this strain has a complete VB12 synthetic pathway, which paves the way for further metabolic engineering studies. The optimal carbon and nitrogen sources are sucrose and corn steep liquor (CSL) plus peptone. The optimal combination of sucrose and CSL was obtained by response surface methodology as they are the most suitable carbon and nitrogen sources, respectively. This strain could produce 140 +/- 4.2 mg L(-1) vitamin B12 after incubating for 7 days in the optimal medium. PMID- 27282167 TI - African Americans with left ventricular hypertrophy and chronic kidney disease: what should we do? PMID- 27282168 TI - [App-based self-monitoring in type 2 diabetes]. AB - BACKGROUND: The success of self-monitoring in the treatment of type 2 diabetes mellitus has already been verified in several studies. To date there are a multitude of smartphone apps which support diabetic patients in systematically recording and analyzing relevant health data; however, most of these smartphone apps are primarily developed for a young target group. OBJECTIVE: As part of this study we examined to what extent a smartphone app for self-monitoring is used by older diabetic patients. METHODS: In this study 36 adults with type 2 diabetes mellitus older than 60 years were included. After a comprehensive training course the participants used the application for 3 months. Reminders for medication, physical activity and diet could be set and recorded health data, such as weight or blood sugar, could be entered into the app. After 3 months the data were analyzed concerning usage behavior and impact on overall health. RESULTS: Data analysis revealed intensive usage of the smartphone app (90 % on a daily basis). Furthermore, according to the patients, after the study period significant improvements in medication adherence and psychological well-being were recorded [t[35] = -2.24, p < 0.05). Additional motivational elements did not influence the usage behavior by older adults. CONCLUSION: Until now only a small proportion of older adults used smartphone health apps, despite the ubiquitous availability. These apps have to be tailored to the requirements of older adults so that the market will be opened up to them. Using self-monitoring apps can help older adults to structure their daily routine despite their disease. PMID- 27282169 TI - Can the use of social media contribute towards Nursing and Midwifery Council revalidation? PMID- 27282170 TI - Acceptance and commitment therapy: an appropriate treatment option for older adults with chronic pain. PMID- 27282171 TI - The Contribution of Sources to the Sustained Elevated Inventory of (137)Cs in Offshore Waters East of Japan after the Fukushima Dai-ichi Nuclear Power Station Accident. AB - We have evaluated the contribution of sources of (137)Cs to the inventory of radiocesium in waters (surface area: 6160 km(2), water volume: 753 km(3)) off Fukushima Prefecture and neighboring prefectures from May 2011 to February 2015. A time-series of the inventory of (137)Cs in the offshore waters revealed a clearly decreasing trend from May 2011 (283.4 TBq) to February 2015 (1.89 TBq). The (137)Cs inventory about four years after the accident was approximately twice the background inventory of 1.1 TBq. The magnitudes of the (137)Cs influxes from sources into offshore waters for periods of 182-183 days were estimated from the first period (1 October 2011 to 31 March 2012: 15.3 TBq) to the last period (1 October 2014 to 31 March 2015: 0.41 TBq). We assumed that three sources contributed (137)Cs: continuous direct discharge from the Fukushima Dai-ichi Nuclear Power Station (FNPS) even after the massive discharge in late March 2011, desorption/dissolution from sediments, and fluvial input. Quantification of these sources indicated that the direct discharge from the FNPS is the principal source of (137)Cs to maintain the relatively high inventory in the offshore area. PMID- 27282172 TI - Promising Cell Configuration for Next-Generation Energy Storage: Li2S/Graphite Battery Enabled by a Solvate Ionic Liquid Electrolyte. AB - Lithium-ion sulfur batteries with a [graphite|solvate ionic liquid electrolyte|lithium sulfide (Li2S)] structure are developed to realize high performance batteries without the issue of lithium anode. Li2S has recently emerged as a promising cathode material, due to its high theoretical specific capacity of 1166 mAh/g and its great potential in the development of lithium-ion sulfur batteries with a lithium-free anode such as graphite. Unfortunately, the electrochemical Li(+) intercalation/deintercalation in graphite is highly electrolyte-selective: whereas the process works well in the carbonate electrolytes inherited from Li-ion batteries, it cannot take place in the ether electrolytes commonly used for Li-S batteries, because the cointercalation of the solvent destroys the crystalline structure of graphite. Thus, only very few studies have focused on graphite-based Li-S full cells. In this work, simple graphite-based Li-S full cells were fabricated employing electrolytes beyond the conventional carbonates, in combination with highly loaded Li2S/graphene composite cathodes (Li2S loading: 2.2 mg/cm(2)). In particular, solvate ionic liquids can act as a single-phase electrolyte simultaneously compatible with both the Li2S cathode and the graphite anode and can further improve the battery performance by suppressing the shuttle effect. Consequently, these lithium-ion sulfur batteries show a stable and reversible charge-discharge behavior, along with a very high Coulombic efficiency. PMID- 27282173 TI - Isocyano Enones: Addition-Cyclization Cascade to Oxazoles. AB - Copper iodide catalyzes the conjugate addition of organometallic and heteroatom nucleophiles to isocyano enones to afford oxazoles. A range of enolates, metalated nitriles, amines, and thiols undergo catalyzed conjugate addition to cyclic and acyclic oxoalkene isocyanides. Mechanistic studies suggest that copper complexation facilitates the nucleophilic attack on the isocyano enone to generate an enolate that cyclizes onto the isocyanide leading to a variety of substituted acyclic or ring-fused oxazoles. PMID- 27282174 TI - Unemployment as a source of mental distress to individuals and their family: Unemployed parents' perceptions during the economic recession. AB - BACKGROUND: Due to the economic recession, several people in Europe became unemployed. This situation may risk their mental health. AIM: This study explored parents' perceptions about their unemployment's effects in daily life during the recession. METHODS: A total of 59 unemployed parents (40.7% fathers and 59.3% mothers), ageing 44.4 years (+/-6.2), answer a question on how the unemployment affected their family lives. Thematic analysis was used to analyse data. RESULTS: The findings suggest that unemployment is a source of adult and youth mental distress and of economic hardship and changes in family relations. CONCLUSION: Support to unemployed individuals and their families could benefit from these insights when granting the needed financial and socioemotional assistance. PMID- 27282175 TI - War and disaster in Sri Lanka: Depression, family adjustment and health among women heading households. AB - BACKGROUND: The civil war, lasting from 1983 to 2009, and the tsunami that struck Southeastern Asia in 2004 were major stressors that changed the demographic landscape of the northern province of Sri Lanka. The composition of families changed dramatically, with an increase in female-headed households, largely due to casualties. The conservation of resources (COR) model was applied in this study to examine relationships between risk and resiliency factors among women heading households, including women widowed by war or disaster. AIMS: This study represents an investigation of the association between predictive risk and resiliency factors (i.e. war damage and loss, social support, economic status, religious participation and discrimination) and outcomes representing well-being (depressive symptoms, family adjustment and a rating of physical health). METHODS: Data from 514 women heading households living in the Kilinochchi district of Sri Lanka were collected through face-to-face interviews in 2013, and associations among the data were estimated using path analysis. RESULTS: Results suggest that resiliency factors that are representative of greater resources generally predicted lower levels of distress and vice versa. CONCLUSION: Further study informing intervention development with women heading households in Sri Lanka is warranted to better understand which individual, family and community resources are most important to mobilize for sustainable recovery efforts to be successful in the decades following war and natural disaster. PMID- 27282176 TI - Caregiving for mental health service users: A study exploring the perceptions of mental health service users and their caregivers in Cape Town, South Africa. AB - BACKGROUND: Our study explores perceptions of the caregiver support for mental health service users (MHSUs) in a low- to middle-income country setting. MATERIALS: We conducted in-depth individual interviews with 16 MHSUs and their treatment partners/caregivers from a treatment partner and text-message intervention study. DISCUSSION: Treatment partners/caregivers felt obligated to care for MHSUs, but had a limited understanding of mental illness. They found supporting adherence to treatment difficult due to a number of factors including violence, food insecurity and substance abuse. CONCLUSION: Socioeconomic and environmental factors affecting the lives of MHSUs have impact on caregiver relationships with MHSUs in their care. PMID- 27282177 TI - Aging: T cell metabolism within tumors. PMID- 27282189 TI - The importance of predictive biomarkers in oncology drug development. PMID- 27282190 TI - Comparison of the Properties of the Handwriting Speed Test (HST) and Detailed Assessment of Speed of Handwriting (DASH): An Exploratory Study. AB - BACKGROUND: Handwriting speed is an important component of students' ability to adequately express their ideas, knowledge and creativity in a timely and effective manner. AIMS: Psychometric properties of the Handwriting Speed Test (HST) and Detailed Assessment of Speed of Handwriting (DASH) and accuracy of the norms for identifying current Australian students with handwriting speed difficulties were examined. METHODS: An exploratory, cross-sectional study was conducted involving students, with and without handwriting difficulties, in Years 3-12 (mean age: 12.0 yrs, SD = 3.0 yrs; range = 7 to 18 yrs) in New South Wales (NSW; Australia). Participants were recruited through occupational therapists and schools. Students completed the HST and all DASH subtests. RESULTS: Thirty-two students with, and 139 students without, handwriting difficulties participated. Intra-rater and inter-rater reliability were found to be excellent; sensitivity was low and specificity high for the HST and DASH. No significant differences were found between test scores and normative data for students without handwriting difficulties (year/age groups with n > 10). CONCLUSIONS: The HST and DASH are reliable assessments of handwriting speed. Further research is required into discriminant validity of the HST and DASH and need for updated norms. PMID- 27282191 TI - Characteristic chromatographic fingerprint study of short-chain fatty acids in human milk, infant formula, pure milk and fermented milk by gas chromatography mass spectrometry. AB - Human milk, infant formula, pure milk and fermented milk as food products or dietary supplements provide a range of nutrients required to both infants and adults. Recently, a growing body of evidence has revealed the beneficial roles of short-chain fatty acids (SCFAs), a subset of fatty acids produced from the fermentation of dietary fibers by gut microbiota. The objective of this study was to establish a chromatographic fingerprint technique to investigate SCFAs in human milk and dairy products by gas chromatography coupled with mass spectrometry. The multivariate method for principal component analysis assessed differences between milk types. Human milk, infant formula, pure milk and fermented milk were grouped independently, mainly because of differences in formic acid, acetic acid, propionic acid and hexanoic acid levels. This method will be important for the assessment of SCFAs in human milk and various dairy products. PMID- 27282192 TI - The relationship between theory of mind and the executive functions: Evidence from patients with frontal lobe damage. AB - "Theory of mind" (ToM) refers to the ability to predict others' thoughts, intentions, beliefs, and feelings. Evidence from neuropsychology and functional imaging indicates that ToM is a domain-specific or modular architecture; however, research in development psychology has suggested that ToM is the full development of the executive functions in individuals. Therefore, the relationship between ToM and the executive functions needs to be clarified. Since the frontal lobe plays a critical role in the abilities of ToM and the executive functions, patients with frontal lobe damage were recruited for the present study. Assessments of ToM and the executive functions were performed on 23 patients with frontal lobe damage and 20 healthy controls. When controlling for the executive functions, significant differences between the patient and normal groups were found in the affective component of ToM, but not in the cognitive component. The present study suggests that in various social situations, executing ToM abilities requires logical reasoning processes provided by the executive functions. However, the reasoning processes of affective ToM are independent of executive functions. PMID- 27282193 TI - Genetic polymorphism of 8 Y-STR loci in native population of Isfahan province in central part of Iran. AB - BACKGROUND: Y-chromosome short tandem repeats (Y-STRs) are genetic markers with practical applications in human identification and population studies. AIM: Here we present the allelic and haplotype frequencies of 8 Y-STR loci most commonly used in forensic medicine in 103 unrelated native males of Isfahan province, central part of Iran. SUBJECTS AND METHODS: The cases were selected on the basis of strict criteria to assure pure native populations of Isfahan origin. DNA extracted from peripheral blood samples and PCR amplified for each marker. Y specific STR loci DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392 and DYS393 were included in this study. RESULTS: The most common alleles for each locus were: DYS19, allele 12; DYS385, allele 12; DYS389I, allele 13; DYS389II, allele 29; DYS390, allele 24; DYS391, allele 10; DYS392, allele 11; and DYS393, allele 13. Gene diversity value was calculated from the allelic frequency for each locus. The average gene diversity was 0.6518. A total of 101 haplotypes were observed in eight Y-specific STR loci, the haplotype diversity was raised to 0.986. CONCLUSION: The results revealed that a set of eight Y-specific STR loci were able to discriminate most of the male individuals in the population studied. A search through the Y Haplotype Reference Database demonstrated 21 matched haplotypes to 160,693 haplotypes, exclusively with Eurasian-European, Eurasian, and Eurasian-Indo Iranian populations. PMID- 27282194 TI - Interplay of Itch and Psyche in Psoriasis: An Update. AB - Itch or pruritus is defined as an unpleasant subjective sensation leading to the need or to the idea of scratching. A number of studies have shown that pruritus is often responsible for marked morbidity, quality of life impairment, and even for increased mortality. Patients suffering from chronic pruritus had also decreased self-esteem, suffer from anxiety or depression and have problems to cope with negative feelings. Several studies documented that itching is a very prevalent symptom of psoriasis affecting more than 70% of individuals and for many patient it is the most bothersome symptom of the disease. While assessing various aspects of itch in psoriatic patients it was found that individuals with pruritus had a significantly lower health-related QoL; patients with pruritus, moreover, were more depressed than those without itching. In conclusion, pruritus is closely related to decreased psychosocial well-being of patients with chronic pruritic skin diseases, including psoriasis. It is important to underscore that itch may interfere with various aspects of patient functioning, emotions and social status and should therefore be adequately addressed while treating patients with psoriasis. PMID- 27282196 TI - Patient-Doctor Relationship in Dermatology: From Compliance to Concordance. AB - The concept of what the doctor-patient relationship should be has changed increasingly in recent years. Previously, an asymmetric relationship was assumed. Compliance and adherence are terms used currently. The concordance model goes further and examines the effectiveness of the mutual process between the doctor and the patient. In this model the interaction is two-sided and involves finding a decision as partners. The origins of this approach are to be found in psychoanalytic theory. PMID- 27282195 TI - Designing, Implementing, and Evaluating Mobile Health Technologies for Managing Chronic Conditions in Older Adults: A Scoping Review. AB - BACKGROUND: The current landscape of a rapidly aging population accompanied by multiple chronic conditions presents numerous challenges to optimally support the complex needs of this group. Mobile health (mHealth) technologies have shown promise in supporting older persons to manage chronic conditions; however, there remains a dearth of evidence-informed guidance to develop such innovations. OBJECTIVES: The purpose of this study was to conduct a scoping review of current practices and recommendations for designing, implementing, and evaluating mHealth technologies to support the management of chronic conditions in community dwelling older adults. METHODS: A 5-stage scoping review methodology was used to map the relevant literature published between January 2005 and March 2015 as follows: (1) identified the research question, (2) identified relevant studies, (3) selected relevant studies for review, (4) charted data from selected literature, and (5) summarized and reported results. Electronic searches were conducted in 5 databases. In addition, hand searches of reference lists and a key journal were completed. Inclusion criteria were research and nonresearch papers focused on mHealth technologies designed for use by community-living older adults with at least one chronic condition, or health care providers or informal caregivers providing care in the home and community setting. Two reviewers independently identified articles for review and extracted data. RESULTS: We identified 42 articles that met the inclusion criteria. Of these, described innovations focused on older adults with specific chronic conditions (n=17), chronic conditions in general (n=6), or older adults in general or those receiving homecare services (n=18). Most of the mHealth solutions described were designed for use by both patients and health care providers or health care providers only. Thematic categories identified included the following: (1) practices and considerations when designing mHealth technologies; (2) factors that support/hinder feasibility, acceptability, and usability of mHealth technologies; and (3) approaches or methods for evaluating mHealth technologies. CONCLUSIONS: There is limited yet increasing use of mHealth technologies in home health care for older adults. A user-centered, collaborative, interdisciplinary approach to enhance feasibility, acceptability, and usability of mHealth innovations is imperative. Creating teams with the required pools of expertise and insight regarding needs is critical. The cyclical, iterative process of developing mHealth innovations needs to be viewed as a whole with supportive theoretical frameworks. Many barriers to implementation and sustainability have limited the number of successful, evidence-based mHealth solutions beyond the pilot or feasibility stage. The science of implementation of mHealth technologies in home-based care for older adults and self-management of chronic conditions are important areas for further research. Additionally, changing needs as cohorts and technologies advance are important considerations. Lessons learned from the data and important implications for practice, policy, and research are discussed to inform the future development of innovations. PMID- 27282197 TI - Cross-cultural adaptation and psychometric properties of an Arabic language version of the Brief Illness Perception Questionnaire in Lebanon. AB - BACKGROUND: Patients' positive illness perceptions (IPs) significantly contribute to treatment success. The Brief Illness Perception Questionnaire (Brief IPQ) is widely used in various diseases for assessing IPs. It was developed in English speaking countries and studies on it in Arab countries are scarce. OBJECTIVES, SETTING AND DESIGN: This observational cross-sectional study aimed to cross culturally adapt the Brief IPQ English version into a modern Arabic language version and determine its psychometric properties in a sample of Lebanese cardiac disease patients. This study was approved by the Institutional Review Board of Saint Joseph University of Beirut, Lebanon. PARTICIPANTS: A convenience sample of 30 patients with cardiac disease were recruited during routine visits to cardiologists' offices in Beirut, Lebanon. Inclusion criteria were at least one cardiac disease for at least 6 months with no acute episode or exacerbation of the disease during the 6 preceding months, age >= 18 years, and the ability to read and comprehend Arabic. The pre-final version of the Brief IPQ Arabic version was tested for face and content validity. The meaning, comprehensibility, and acceptability were studied by individual interviews. For discriminant validity and internal consistency of the Brief IPQ Arabic version (Brief IPQ-Ar), 100 patients were recruited in a similar manner using the same inclusion criteria. To assess reproducibility, 30 patients, selected randomly from the 100 patients, filled the questionnaire a second time, 3-4 weeks after its first administration and under the same conditions. MAIN OUTCOME MEASURES: Psychometric properties of the Brief IPQ-Ar among Lebanese patients suffering from cardiac diseases. RESULTS: Semantic equivalence between the Brief IPQ-Ar questions and patients' descriptions was 100%. Cronbach's alpha was 0.717, which shows good internal consistency. Reproducibility was satisfactory (ICC values>0.776). Moreover, the Brief IPQ-Ar discriminated participants according to the type of cardiac disease and treatment-related characteristics. CONCLUSIONS: We confirm that the Brief IPQ Ar is appropriate for exploring IPs in cardiac disease patients whose first language is Arabic. Further research should be conducted to test this Arabic version in other types of diseases. PMID- 27282198 TI - Results from a large targeted screening program for alpha-1-antitrypsin deficiency: 2003 - 2015. AB - BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is an autosomal codominant inherited disease that is significantly underdiagnosed. We have previously shown that the combination of an awareness campaign with the offer of free diagnostic testing results in the detection of a relevant number of severely deficient AATD patients. The present study provides an update on the results of our targeted screening program (German AAT laboratory, University of Marburg) covering a period from August 2003 to May 2015. METHODS: Diagnostic AATD detection test kits were offered free of charge. Dried blood samples were sent to our laboratory and used for the semiquantitative measurement of the AAT-level (nephelometry) and the detection of the S- or Z-allele (PCR). Isoelectric focusing was performed when either of the initial tests was indicative for at least one mutation. Besides, we evaluated the impact of additional screening efforts and the changes of the detection rate over time, and analysed the relevance of clinical parameters in the prediction of severe AATD. RESULTS: Between 2003 and 2015, 18,638 testing kits were analysed. 6919 (37.12 %) carried at least one mutation. Of those, we identified 1835 patients with severe AATD (9.82 % of the total test population) including 194 individuals with rare genotypes. Test initiatives offered to an unselected population resulted in a dramatically decreased detection rate. Among clinical characteristics, a history of COPD, emphysema, and bronchiectasis were significant predictors for Pi*ZZ, whereas a history of asthma, cough and phlegm were predictors of not carrying the genotype Pi*ZZ. CONCLUSION: A targeted screening program, combining measures to increase awareness with cost-free diagnostic testing, resulted in a high rate of AATD detection. The clinical data suggest that testing should be primarily offered to patients with COPD, emphysema, and/or bronchiectasis. PMID- 27282199 TI - Comparison of small-area deprivation measures as predictors of chronic disease burden in a low-income population. AB - BACKGROUND: Measures of small-area deprivation may be valuable in geographically targeting limited resources to prevent, diagnose, and effectively manage chronic conditions in vulnerable populations. We developed a census-based small-area socioeconomic deprivation index specifically to predict chronic disease burden among publically insured Medicaid recipients in South Carolina, a relatively poor state in the southern United States. We compared the predictive ability of the new index with that of four other small-area deprivation indicators. METHODS: To derive the ZIP Code Tabulation Area-Level Palmetto Small-Area Deprivation Index (Palmetto SADI), we evaluated ten census variables across five socioeconomic deprivation domains, identifying the combination of census indicators most highly correlated with a set of five chronic disease conditions among South Carolina Medicaid enrollees. In separate validation studies, we used both logistic and spatial regression methods to assess the ability of Palmetto SADI to predict chronic disease burden among state Medicaid recipients relative to four alternative small-area socioeconomic deprivation measures: the Townsend index of material deprivation; a single-variable poverty indicator; and two small-area designations of health care resource deprivation, Primary Care Health Professional Shortage Area and Medically Underserved Area/Medically Underserved Population. RESULTS: Palmetto SADI was the best predictor of chronic disease burden (presence of at least one condition and presence of two or more conditions) among state Medicaid recipients compared to all alternative deprivation measures tested. CONCLUSIONS: A low-cost, regionally optimized socioeconomic deprivation index, Palmetto SADI can be used to identify areas in South Carolina at high risk for chronic disease burden among Medicaid recipients and other low-income Medicaid-eligible populations for targeted prevention, screening, diagnosis, disease self-management, and care coordination activities. PMID- 27282201 TI - Effects of Titanium Layer Oxygen Scavenging on the High-k/InGaAs Interface. AB - One of the main challenges in the path to incorporating InGaAs based metal-oxide semiconductor structures in nanoelectronics is the passivation of high-k/InGaAs interfaces. Here, the oxygen scavenging effect of thin Ti layers on high-k/InGaAs gate stacks was studied. Electrical measurements and synchrotron X-ray photoelectron spectroscopy measurements, with in situ metal deposition, were used. Oxygen removal from the InGaAs native oxide surface layer remotely through interposed Al2O3 and HfO2 layers observed. Synchrotron X-ray photoelectron spectroscopy has revealed a decrease in the intensity of InOx features relative to In in InGaAs after Ti deposition. The signal ratio decreases further after annealing. In addition, Ti 2p spectra clearly show oxidation of the thin Ti layer in the ultrahigh vacuum XPS environment. Using capacitance-voltage and conductance-voltage measurements, Pt/Ti/Al2O3/InGaAs and Pt/Al2O3/InGaAs capacitors were characterized both before and after annealing. It was found that the remote oxygen scavenging from the oxide/semiconductor interface using a thin Ti layer can influence the density of interface traps in the high-k/InGaAs interface. PMID- 27282200 TI - Temple-Baraitser Syndrome and Zimmermann-Laband Syndrome: one clinical entity? AB - BACKGROUND: KCNH1 encodes a voltage-gated potassium channel that is predominantly expressed in the central nervous system. Mutations in this gene were recently found to be responsible for Temple-Baraitser Syndrome (TMBTS) and Zimmermann Laband syndrome (ZLS). METHODS: Here, we report a new case of TMBTS diagnosed in a Lebanese child. Whole genome sequencing was carried out on DNA samples of the proband and his parents to identify mutations associated with this disease. Sanger sequencing was performed to confirm the presence of detected variants. RESULTS: Whole genome sequencing revealed three missense mutations in TMBTS patient: c.1042G > A in KCNH1, c.2131 T > C in STK36, and c.726C > A in ZNF517. According to all predictors, mutation in KCNH1 is damaging de novo mutation that results in substitution of Glycine by Arginine, i.e., p.(Gly348Arg). This mutation was already reported in a patient with ZLS that could affect the connecting loop between helices S4-S5 of KCNH1 with a gain of function effect. CONCLUSIONS: Our findings demonstrate that KCNH1 mutations cause TMBTS and expand the mutational spectrum of KCNH1 in TMBTS. In addition, all cases of TMBTS were reviewed and compared to ZLS. We suggest that the two syndromes are a continuum and that the variability in the phenotypes is the result of the involvement of genetic modifiers. PMID- 27282202 TI - Quantitative Analysis of Critical Factors for the Climate Impact of Landfill Mining. AB - Landfill mining has been proposed as an innovative strategy to mitigate environmental risks associated with landfills, to recover secondary raw materials and energy from the deposited waste, and to enable high-valued land uses at the site. The present study quantitatively assesses the importance of specific factors and conditions for the net contribution of landfill mining to global warming using a novel, set-based modeling approach and provides policy recommendations for facilitating the development of projects contributing to global warming mitigation. Building on life-cycle assessment, scenario modeling and sensitivity analysis methods are used to identify critical factors for the climate impact of landfill mining. The net contributions to global warming of the scenarios range from -1550 (saving) to 640 (burden) kg CO2e per Mg of excavated waste. Nearly 90% of the results' total variation can be explained by changes in four factors, namely the landfill gas management in the reference case (i.e., alternative to mining the landfill), the background energy system, the composition of the excavated waste, and the applied waste-to-energy technology. Based on the analyses, circumstances under which landfill mining should be prioritized or not are identified and sensitive parameters for the climate impact assessment of landfill mining are highlighted. PMID- 27282203 TI - [Prenatal treatment with magnesium sulphate: Initial clinical outcomes in pre term infants less than 29 weeks and correlation with neonatal magnesium levels]. AB - INTRODUCTION: Antenatal magnesium sulphate (MgSO4) administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years. The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO4, as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. MATERIAL AND METHODS: A prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universitario de Vigo from December 2012 to July 2015. Comparative analysis was performed on the perinatal outcomes, neonatal morbidity, mortality, and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group. RESULTS: A total of 42 neonates were included in the study. The mothers of 28 of them had received MgSO4 as a neuroprotective agent. Statistical significance was obtained in the mortality variable. There were no significant differences in the rest of studied variables. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24hours of life (r2 0.436; P<.001). CONCLUSIONS: A lower mortality was observed in the group that had been exposed to MgS04. No significant side effects were found as a result of administering of MgS04. The MgS04 dose received by mother has a linear relationship with the magnesium levels obtained in neonates. PMID- 27282204 TI - Ultrasound in the diagnosis of asymptomatic hyperuricaemia and gout. AB - The increase in serum urate concentrations (hyperuricaemia, >=7.0mg/dL) creates crystals, which promote inflammation and joint lesions. Ultrasonography can reveal these urate deposits. The presence of crystals suggests that a patient with hyperuricaemia is actually experiencing asymptomatic gout, and that a patient with gout without subcutaneous tophi could experience tophaceous gout. The information offered by ultrasound (double contour sign and hyperechoic concretions mimicking clouds) enables a more specific classification of hyperuricaemia and gout. Additionally, this information can lead to relevant changes in terms of the diagnosis and therapeutic approach for patients with hyperuricaemia and gout. PMID- 27282205 TI - Pleural ultrasound for clinicians. AB - Pleural ultrasonography is useful for identifying and characterising pleural effusions, solid pleural lesions (nodules, masses, swellings) and pneumothorax. Pleural ultrasonography is also considered the standard care for guiding interventionist procedures on the pleura at the patient's bedside (thoracentesis, drainage tubes, pleural biopsies and pleuroscopy). Hospitals should promote the acquisition of portable ultrasound equipment to increase the patient's safety. PMID- 27282206 TI - C-reactive protein in pleural fluid. Does it help predict complicated parapneumonic effusions? PMID- 27282207 TI - Integracides H-J: New tetracyclic triterpenoids from the endophytic fungus Fusarium sp. AB - Three new tetracyclic triterpenoids namely, integracides H (1), I (4), and J (5), along with integracides B (3) and F (2) have been isolated from the endophytic fungus Fusarium sp. isolated from the roots of Mentha longifolia L. (Labiatae) growing in Saudi Arabia. The structure elucidation of the isolated compounds was achieved by spectroscopic analysis including UV, IR, 1D ((1)H and (13)C) and 2D ((1)H(1)H COSY, TOCSY, HSQC, HMBC, and NOESY) NMR as well as HRESIMS and comparison with literature data. Integracides H (1) and J (5) showed significant anti-leishmanial activity towards Leishmania donovani with IC50 values of 4.75 and 3.29MUM, respectively compared to pentamidine (IC50 6.35MUM). Moreover, they displayed potent cytotoxic activity towards BT-549, SKOV-3, and KB cell lines with IC50 values of 1.82, 1.32, and 0.18MUM and 2.46, 3.01, and 2.54MUM, respectively. PMID- 27282208 TI - Characterization and preparation of oligomeric procyanidins from Litchi chinensis pericarp. AB - The main purpose of this study is to characterize and prepare A-type oligomeric procyanidins from litchi pericarp (Litchi chinensis Baila). The variety of oligomeric procyanidins was characterized by LC-ESI-MS analysis. There were (+) catechin, (-)-epicatechin, twelve dimers and six trimers of procyanidins were found in litchi pericarp extracts, and A-type procyanidins were much more abundant than B-type procyanidins. The main flavan-3-ol monomer and oligomeric procyanidins in litchi pericarp were (-)-epicatechin, A-type dimers (A1 and A2) and trimer (epicatechin-(4beta-8, 2beta-O-7)-epicatechin- (4beta-8)-epicatechin). Procyanidin A1 (epicatechin-(4beta-8, 2beta-O-7)-catechin) was identified by NMR in litchi pericarp for the first time. (-)-Epicatechin and oligomeric procyanidins were prepared by the combination of AB-8 column chromatography and Toyopearl HW-40S column chromatography. The results showed that each fraction predominantly owned a single compound and gave a high yield with (-)-epicatechin, A-type dimers (A1 and A2) and trimer, suggesting a useful method to obtain pure ( )-epicatechin and A-type oligomeric procyanidins. PMID- 27282209 TI - Dermal permeation data and models for the prioritization and screening-level exposure assessment of organic chemicals. AB - High-throughput screening (HTS) models are being developed and applied to prioritize chemicals for more comprehensive exposure and risk assessment. Dermal pathways are possible exposure routes to humans for thousands of chemicals found in personal care products and the indoor environment. HTS exposure models rely on skin permeability coefficient (KP; cm/h) models for exposure predictions. An initial database of approximately 1000 entries for empirically-based KP data was compiled from the literature and a subset of 480 data points for 245 organic chemicals derived from testing with human skin only and using only water as a vehicle was selected. The selected dataset includes chemicals with log octanol water partition coefficients (KOW) ranging from -6.8 to 7.6 (median=1.8; 95% of the data range from -2.5 to 4.6) and molecular weight (MW) ranging from 18 to 765g/mol (median=180); only 3% >500g/mol. Approximately 53% of the chemicals in the database have functional groups which are ionizable in the pH range of 6 to 7.4, with 31% being appreciably ionized. The compiled log KP values ranged from 5.8 to 0.1cm/h (median=-2.6). The selected subset of the KP data was then used to evaluate eight representative KP models that can be readily applied for HTS assessments, i.e., parameterized with KOW and MW. The analysis indicates that a version of the SKINPERM model performs the best against the selected dataset. Comparisons of representative KP models against model input parameter property ranges (sensitivity analysis) and against chemical datasets requiring human health assessment were conducted to identify regions of chemical properties that should be tested to address uncertainty in KP models and HTS exposure assessments. PMID- 27282210 TI - Dupuytren Disease Infiltrating a Full-Thickness Skin Graft. AB - Although the role of the skin in the development and propagation of Dupuytren disease remains unclear, dermofasciectomy and full-thickness skin grafting (FTSG) appears to delay recurrence. In 2011, a 71-year-old, left-handed man presented with recurrent Dupuytren disease in the dominant hand. In 1991, he originally underwent a primary dermofasciectomy and FTSG for Dupuytren disease involving the palmar skin. Twenty years later, the left middle finger was drawn into flexion by a recurrent cord, and the old graft and adjacent palmar skin were clinically involved by fibromatosis. We performed a revision dermofasciectomy and FTSG. Microscopic analysis of the excised graft demonstrated dense infiltration of the entire skin graft by Dupuytren disease, with areas of active and burnt-out fibromatosis distinct from hypertrophic scarring. This report of Dupuytren fibromatosis infiltrating a skin graft raises questions about the pathophysiology of Dupuytren disease. PMID- 27282211 TI - Effect of LTRA on IP-10-induced eosinophil adhesion to ICAM-1. PMID- 27282212 TI - Endotypes of allergic diseases and asthma: An important step in building blocks for the future of precision medicine. AB - Discoveries from basic science research in the last decade have brought significant progress in knowledge of pathophysiologic processes of allergic diseases, with a compelling impact on understanding of the natural history, risk prediction, treatment selection or mechanism-specific prevention strategies. The view of the pathophysiology of allergic diseases developed from a mechanistic approach, with a focus on symptoms and organ function, to the recognition of a complex network of immunological pathways. Several subtypes of inflammation and complex immune-regulatory networks and the reasons for their failure are now described, that open the way for the development of new diagnostic tools and innovative targeted-treatments. An endotype is a subtype of a disease condition, which is defined by a distinct pathophysiological mechanism, whereas a disease phenotype defines any observable characteristic of a disease without any implication of a mechanism. Another key word linked to disease endotyping is biomarker that is measured and evaluated to examine any biological or pathogenic processes, including response to a therapeutic intervention. These three keywords will be discussed more and more in the future with the upcoming efforts to revolutionize patient care in the direction of precision medicine and precision health. The understanding of disease endotypes based on pathophysiological principles and their validation across clinically meaningful outcomes in asthma, allergic rhinitis, chronic rhinosinusitis, atopic dermatitis and food allergy will be crucial for the success of precision medicine as a new approach to patient management. PMID- 27282213 TI - Application of failure mode and effect analysis in an assisted reproduction technology laboratory. AB - Assisted reproduction technology laboratories have a very high degree of complexity. Mismatches of gametes or embryos can occur, with catastrophic consequences for patients. To minimize the risk of error, a multi-institutional working group applied failure mode and effects analysis (FMEA) to each critical activity/step as a method of risk assessment. This analysis led to the identification of the potential failure modes, together with their causes and effects, using the risk priority number (RPN) scoring system. In total, 11 individual steps and 68 different potential failure modes were identified. The highest ranked failure modes, with an RPN score of 25, encompassed 17 failures and pertained to "patient mismatch" and "biological sample mismatch". The maximum reduction in risk, with RPN reduced from 25 to 5, was mostly related to the introduction of witnessing. The critical failure modes in sample processing were improved by 50% in the RPN by focusing on staff training. Three indicators of FMEA success, based on technical skill, competence and traceability, have been evaluated after FMEA implementation. Witnessing by a second human operator should be introduced in the laboratory to avoid sample mix-ups. These findings confirm that FMEA can effectively reduce errors in assisted reproduction technology laboratories. PMID- 27282214 TI - Individual differences in behavioral activation and cardiac vagal control influence affective startle modification. AB - The startle response (SR) has a close relationship with stress responses. Startle modification (SRM) has been widely used to study stress disorders (e.g., posttraumatic stress disorder). The framework of the behavioral inhibition and activation systems (BIS/BAS) has been thought to correspond with withdrawal and approach motivational processes underlying affective SRM and can influence stress reactivity. Vagally-mediated cardiac activity as indexed by heart rate variability (HRV) has been associated with SRM and regulatory processes during stress. In the present study, the influence of individual differences in the BIS/BAS and resting HRV on affective SRM were examined. Eighty-six subjects viewed affective pictures while acoustic SR stimuli were delivered. Individual differences in motivation were measured by the BIS/BAS scales. The magnitude of SR was assessed as electromyographic activity of the SR eyeblink during pictures of different valences. Resting HRV was derived from electrocardiography. In contrast to previous studies, the present results showed that startle inhibition and potentiation were related to BAS and HRV, but not to BIS. There was also an interaction of BAS and HRV, indicating that the relationship between HRV and SRM strengthened as BAS scores decreased. The present findings suggest that BAS may relate to both withdrawal and approach, and trait stress reactivity is influenced by BAS and cardiac vagal activity. In addition, BAS moderates the relationship between cardiac vagal activity and SRM. These findings have both theoretical and practical implications for the study of SRM, stress disorders, and health. PMID- 27282215 TI - Use of an autologous patch of platelet-rich fibrin (PRF) to prevent leakage after sleeve gastrectomy: A prospective observational study of 62 cases. PMID- 27282216 TI - Antibiotic-impregnated calcium phosphate cement as part of a comprehensive treatment for patients with established orthopaedic infection. AB - BACKGROUND: The treatment of established orthopaedic infection is challenging. While the main focus of treatment is wide surgical debridement, systemic and local antibiotic administration are important adjuvant therapies. Several reports have described the clinical use of antibiotic-impregnated calcium phosphate cement (CPC) to provide local antibiotic therapy for bone infections. However, these were all individual case reports, and no case series have been reported. We report a case series treated by a single surgeon using antibiotic-impregnated CPC as part of a comprehensive treatment plan in patients with established orthopaedic infection. METHODS: We enrolled 13 consecutive patients with osteomyelitis (n = 6) or infected non-union (n = 7). Implantation of antibiotic impregnated CPC was performed to provide local antibiotic therapy as part of a comprehensive treatment plan that also included wide surgical debridement, systemic antibiotic therapy, and subsequent second-stage reconstruction surgery. We investigated the rate of successful infection eradication and systemic/local complications. The concentration of antibiotics in the surgical drainage fluids, blood, and recovered CPC (via elution into a phosphate-buffered saline bath) were measured. RESULTS: The mean follow-up period after surgery was 50.4 (range, 27 73) months. There were no cases of infection recurrence during follow-up. No systemic toxicity or local complications from the implantation of antibiotic impregnated CPC were observed. The vancomycin concentration in the fluid from surgical drainage (n = 6) was 527.1 +/- 363.9 MUg/mL on postoperative day 1 and 224.5 +/- 198.4 MUg/mL on postoperative day 2. In patients who did not receive systemic vancomycin therapy (n = 3), the maximum serum vancomycin level was <0.8 MUg/mL. In vitro vancomycin elution was observed from the CPC that was surgically retrieved (n = 2). CONCLUSIONS: Implantation of antibiotic-impregnated CPC is an option to provide local antibiotic therapy as part of a comprehensive treatment plan. PMID- 27282217 TI - Importance of the lateral parabrachial nucleus to sodium balance in fluid depleted rats. AB - The lateral parabrachial nucleus (LPBN) exerts an important inhibitory influence for the control of sodium and water intake. However, the importance of LPBN on renal responses and cardiovascular changes during extracellular dehydration are still unknown. Here we investigated the effects of bilateral injections of moxonidine (alpha2-adrenergic and imidazoline receptor agonist) on renal and cardiovascular changes in fluid-depleted rats. Male Wistar rats (n=4-8 per group) with bilateral stainless steel guide-cannulas implanted into the LPBN were treated with subcutaneous furosemide (10mg/kg)+captopril (5mg/kg) to induce fluid depletion. Forty-five min later vehicle or moxonidine (0.5nmol/0.2MUl) were bilaterally injected into the LPBN. In fluid-depleted rats, moxonidine produced strong 0.3M NaCl and water intake without noticeable changes in cardiovascular parameters. Moxonidine did not change sodium excretion (488+/-135, vs. vehicle: 376+/-75MUEq/1h) or urinary volume (2.5+/-0.7, vs. vehicle: 2.5+/-0.3ml/1h) in fluid-depleted rats without access to fluids for rehydration. However, moxonidine decreased natriuresis (462+/-127, vs. vehicle: 888+/-122MUEq/1h) and diuresis (2.5+/-0.5, vs. vehicle: 4.5+/-0.5ml/1h) in fluid-depleted rats submitted to i.g. rehydration. These data suggest that alpha2-adrenergic mechanism of the LPBN facilitates sodium/water retention and body fluid volume expansion during extracellular dehydration. PMID- 27282218 TI - Removal of Caval and Right Atrial Thrombi and Masses Using the AngioVac Device: Initial Operative Experience. AB - PURPOSE: To describe initial single-center experience with a thrombectomy device in managing right atrial and caval thrombi, tumors, and vegetations. MATERIALS AND METHODS: A retrospective analysis of AngioVac thrombectomy performed in 16 patients (mean age 53 y +/- 13; 8 men, 8 women) between August 2013 and August 2015 was performed. Indications included right atrial mass/thrombus (6/16; 37.5%) and iliocaval thrombus (10/16; 62.5%). Procedural success was defined as aspiration of > 70% volume of atrial mass/thrombus or restoration of antegrade caval flow. RESULTS: Procedural success was achieved in 4/6 (67%) right atrial masses/thrombi and 10/10 (100%) caval thrombi. All patients (8/8; 100%) with caval thrombus presenting with swelling/edema had improvement or resolution of symptoms. There were no procedural or periprocedural mortalities; complications included one major (6.3%; intraprocedural pulmonary embolus) and one minor (6.3%; access site hematoma not requiring transfusion) complication. Of 16 patients, 14 (87.5%) survived to discharge at a mean of 10 days +/- 8 (range, 1-23 d), and 12 patients (75%) were alive at last known follow-up at a mean of 385 days +/- 267 (range, 63-730 d). At a mean of 194 days +/- 177 (range, 41-372 d), 4/16 (25%) patients were dead; no death was related to AngioVac thrombectomy. At a mean of 66 days +/- 21 (range, 49-90 d) after intervention, 3/14 (21.4%) cases with procedural success had local recurrence of mass/thrombus. CONCLUSIONS: AngioVac thrombectomy can be performed with high procedural success with clinical benefit in patients with right atrial and caval masses/thrombi. PMID- 27282219 TI - Social Media: The New Impact Factor? PMID- 27282220 TI - Resolving new ultrastructural features of cytokinetic abscission with soft-X-ray cryo-tomography. AB - Mammalian cytokinetic abscission is mediated by the ESCRT membrane fission machinery. While much has been clarified on the topology and kinetics of abscission through high-resolution microscopy, key questions regarding the mechanism of abscission remain open. Here we apply cryogenic soft-X-ray tomography to elucidate new ultrastructural details in the intercellular membrane bridge connecting cells undergoing abscission. In particular, we resolve defined ring-like structures inside the midbody dark zone that have been inaccessible to EM, and identify membrane extrusions at the abscission sites. In cells at late stages of abscission we resolve a complex array of helical spirals, extending the structural information obtained by EM. Our results highlight the advantages of soft-X-ray tomography and emphasize the importance of using complementary approaches for characterizing cellular structures. Notably, by providing new structural data from intact cells we present a realistic view on the topology of abscission and suggest new mechanistic models for ESCRT mediated abscission. PMID- 27282221 TI - Corrigendum: Substoichiometric inhibition of transthyretin misfolding by immune targeting sparsely populated misfolding intermediates: a potential diagnostic and therapeutic for TTR amyloidoses. PMID- 27282222 TI - Developmental model of an automatic production of the human bronchial tree based on L-system. AB - BACKGROUND AND OBJECTIVE: The human lungs exchange air with the external environment via the conducting airways. The application of an anatomically accurate model of the conducting airways can be helpful for simulating gas exchange and fluid distribution throughout the bronchial tree in the lung. METHODS: In the current study, Lindenmayer system (L-system) has been formulated to generate the bronchial tree structure in a human lung. It has been considered that the structure of the bronchial tree is divided into two main segments: 1) The central airways (from the trachea to segmental bronchi) and 2) the dichotomous structure (from segmental bronchi to terminal bronchioles). Two sets of parametric rewriting rules which can be used to develop central and peripheral airways have been proposed; the first set used to develop central airways consists of seven rules, while the second rule set contains four rules. RESULTS: The proposed model is capable of generating bronchial tree inside the volume of the host lung; and comparison of the resulting model with those reported in the literature shows that the morphometric characteristics of L-system structure are in good agreement with their corresponding experimental data. CONCLUSION: The resulting model can be used to obtain a mathematical model required for the study of transport phenomena occurring in the lung during respiration. PMID- 27282223 TI - Automatic detection and segmentation of sperm head, acrosome and nucleus in microscopic images of human semen smears. AB - BACKGROUND AND OBJECTIVE: Manual assessment of sperm morphology is subjective and error prone so developing automatic methods is vital for a more accurate assessment. The first step in automatic evaluation of sperm morphology is sperm head detection and segmentation. In this paper a complete framework for automatic sperm head detection and segmentation is presented. METHODS: After an initial thresholding step, the histogram of the Hue channel of HSV color space is used, in addition to size criterion, to discriminate sperm heads in microscopic images. To achieve an improved segmentation of sperm heads, an edge-based active contour method is used. Also a novel tail point detection method is proposed to refine the segmentation by locating and removing the midpiece from the segmented head. An algorithm is also proposed to separate the acrosome and nucleus using morphological operations. Dice coefficient is used to evaluate the segmentation performance. The proposed methods are evaluated using a publicly available dataset. RESULTS: The proposed method has achieved segmentation accuracy of 0.92 for sperm heads, 0.84 for acrosomes and 0.87 for nuclei, with the standard deviation of 0.05, which significantly outperforms the current state-of-the-art. Also our tail detection method achieved true detection rate of 96%. CONCLUSIONS: In this paper we presented a complete framework for sperm detection and segmentation which is totally automatic. It is shown that using active contours can improve the segmentation results of sperm heads. Our proposed algorithms for tail detection and midpiece removal further improved the segmentation results. The results indicate that our method achieved higher Dice coefficients with less dispersion compared to the existing solutions. PMID- 27282224 TI - Clinical testing of propofol geriatic dose for sedation designed via in silico trial. AB - The geriatric population shows significant physiological changes due to aging and the multiple co-morbidities that they often present. Conventionally the propofol sedation dose for patients older than 65 years is 80% of the adult dose. We performed an in silico trial for elderly population and the results showed that the necessary simulated dose of propofol was lower than the conventional dose; therefore, a clinical trial was implemented to test three different propofol doses, two of them lower than the conventional dose, during a pacemaker implantation. The clinical trial showed that there was no clinical difference between the effects of the doses. A BIS monitor was used to measure the level of sedation, which proved to be adequate and well maintained by all patients. All the patients maintained an acceptable level of sedation, measured by a BIS monitor. Since propofol has some dose-dependent secondary effects, the use of lower doses, especially the ones designed for this age group, helps to avoid them. PMID- 27282225 TI - CopyMean: A new method to predict monotone missing values in longitudinal studies. AB - BACKGROUND: Longitudinal studies are those in which the same variable is repeatedly measured at different times. More likely than others, these studies suffer from missing values. Because the missing values may impact the statistical analyses, it is important that they be dealt with properly. METHODS: In this paper, we present "CopyMean", a new method to impute (predict) monotone missing values. We compared its efficiency to sixteen imputation methods dedicated to the treatment of missing values in longitudinal data. All these methods were tested on four datasets, real or artificial, presenting markedly different caracteristics. RESULTS: The analysis showed that CopyMean was more efficient in almost all situations. PMID- 27282226 TI - Blood flow suspension in tapered stenosed arteries for Walter's B fluid model. AB - BACKGROUND AND OBJECTIVES: In the present article, I have studied the blood flow of a Walter's B fluid through a tapered artery with a stenosis. The problem is modeled in cylindrical coordinates system. METHODS RESULTS CONCLUSIONS: The analytical solutions have been carried out using regular perturbation method by taking alpha as perturbation parameter. The expressions for velocity, resistance impedance, wall shear stress and shearing stress at the stenosis throat have been evaluated. The graphical results of different types of tapered arteries (i.e. converging tapering, diverging tapering, non-tapered artery) have been examined for different parameters of interest. PMID- 27282227 TI - Association between anxiety state and mitral valve disorders: A Taiwanese population-wide observational study. AB - BACKGROUND AND OBJECTIVE: Despite substantial research progress in concurrent diseases, for instance comorbidities involving anxiety state (AS) and mitral valve disorders (MVD), the current measures and care are limited and no consensus about their association has yet been reached. Hence, this study aims to analyze the prevalence and association between AS and MVD among Taiwanese population. METHODS: We employed phenome-wide association study (PWAS) portal to investigate the association between AS and MVD using claim data of Taiwan's National Health Insurance Research Database (NHIRD) from year 2000 to 2002. Association strength between AS and MVD was analyzed among overall age and gender groups. RESULTS: We found an overall stronger association between AS and MVD, which was significantly higher in younger age group (OR 15, 95% CI 14.82-16.88) than in the elderly age group (OR 1.99, 95% CI 1.76-2.24). Also, the study reveals a higher incidence of co-occurrence in females than males, particularly in age group of 40-49. CONCLUSIONS: Based on our results showing considerable strength of association between AS and MVD, this study suggests the necessity of MVD assessment in all patients with AS, particularly in younger females. Moreover, we also propose psychotherapeutic as well as pharmacologic intervention for comorbidity-based pathologies to better the quality care for high-need Taiwanese population. PMID- 27282228 TI - Improving the discrimination of hand motor imagery via virtual reality based visual guidance. AB - While research on the brain-computer interface (BCI) has been active in recent years, how to get high-quality electrical brain signals to accurately recognize human intentions for reliable communication and interaction is still a challenging task. The evidence has shown that visually guided motor imagery (MI) can modulate sensorimotor electroencephalographic (EEG) rhythms in humans, but how to design and implement efficient visual guidance during MI in order to produce better event-related desynchronization (ERD) patterns is still unclear. The aim of this paper is to investigate the effect of using object-oriented movements in a virtual environment as visual guidance on the modulation of sensorimotor EEG rhythms generated by hand MI. To improve the classification accuracy on MI, we further propose an algorithm to automatically extract subject specific optimal frequency and time bands for the discrimination of ERD patterns produced by left and right hand MI. The experimental results show that the average classification accuracy of object-directed scenarios is much better than that of non-object-directed scenarios (76.87% vs. 69.66%). The result of the t test measuring the difference between them is statistically significant (p = 0.0207). When compared to algorithms based on fixed frequency and time bands, contralateral dominant ERD patterns can be enhanced by using the subject-specific optimal frequency and the time bands obtained by our proposed algorithm. These findings have the potential to improve the efficacy and robustness of MI-based BCI applications. PMID- 27282229 TI - An effective model for store and retrieve big health data in cloud computing. AB - BACKGROUND AND OBJECTIVE: The volume of healthcare data including different and variable text types, sounds, and images is increasing day to day. Therefore, the storage and processing of these data is a necessary and challenging issue. Generally, relational databases are used for storing health data which are not able to handle the massive and diverse nature of them. METHODS: This study aimed at presenting the model based on NoSQL databases for the storage of healthcare data. Despite different types of NoSQL databases, document-based DBs were selected by a survey on the nature of health data. The presented model was implemented in the Cloud environment for accessing to the distribution properties. Then, the data were distributed on the database by applying the Shard property. RESULTS: The efficiency of the model was evaluated in comparison with the previous data model, Relational Database, considering query time, data preparation, flexibility, and extensibility parameters. The results showed that the presented model approximately performed the same as SQL Server for "read" query while it acted more efficiently than SQL Server for "write" query. Also, the performance of the presented model was better than SQL Server in the case of flexibility, data preparation and extensibility. CONCLUSIONS: Based on these observations, the proposed model was more effective than Relational Databases for handling health data. PMID- 27282230 TI - Do false positive alerts in naive clinical decision support system lead to false adoption by physicians? A randomized controlled trial. AB - OBJECTIVES: False positive alerts in patient-safety-related clinical decision support systems (CDSS) are defined as alerts which incorrectly prompt when no risk patients are encountered. It is an unfavorable condition which may potentially mislead physicians. The aim is to investigate physician responses toward false positive (FP) and true positive (TP) alerts in CDSS for the prevention of contrast-induced nephropathy (CIN). METHODS: A two-arm cluster randomized controlled trial was conducted in university hospitals. Eligible physicians were randomized to receive alert intervention or no intervention (groups 1 and 2, respectively). The alert system was embedded with a deliberately non-specific risk detection tool in order to generate TP and FP alerts. The naive alert system would alert the physician to cancel the order regardless of the patient being at-risk or not at-risk. CIN risk was stratified as at-risk and no risk according to a patient's pre-existing renal function. Contrast imaging order cancellation rate was measured as primary outcome. RESULTS: 3802 contrast enhanced examination orders from 66 physicians were analyzed. Demographic data and risk distributions of patients were similar and well-balanced between two groups. In the intervention group, a total of 1892 alerts were generated (332 TP alerts and 1560 FP alerts). Order-cancellation rates were 5.1% versus 1.4% in groups 1 and 2 for at-risk patients (relative risk [RR] = 3.69) from TP alerts, and 1.0% versus 1.4% for no-risk patients (RR = 0.71) from FP alerts. Using generalized linear model with generalized estimating equation, the FP alerts had no order-cancellation effect when compared to the control arm (adjusted RR = 0.69; 95%CI, 0.36-1.32). The TP alerts had a larger order-cancellation effect than that of the control arm (adjusted RR = 2.95; 95%CI, 0.94-9.27), which revealed a marginal trend toward significance. However, the effect was not statistically significant (adjusted RR = 1.24; 95%CI, 0.71-2.18) if TP and FP alerts were mixed. CONCLUSIONS: Physicians are not likely to adopt recommendations provided by false positive alerts in patient-safety-related CDSS. If reporting only the adoption rate of CDSS as a whole without differentiating between TP and FP alerts, the effects of TP and FP alerts will be mixed, and thus, will lead to an underestimation of system effectiveness. PMID- 27282231 TI - A review of the applications of data mining and machine learning for the prediction of biomedical properties of nanoparticles. AB - This article presents a comprehensive review of applications of data mining and machine learning for the prediction of biomedical properties of nanoparticles of medical interest. The papers reviewed here present the results of research using these techniques to predict the biological fate and properties of a variety of nanoparticles relevant to their biomedical applications. These include the influence of particle physicochemical properties on cellular uptake, cytotoxicity, molecular loading, and molecular release in addition to manufacturing properties like nanoparticle size, and polydispersity. Overall, the results are encouraging and suggest that as more systematic data from nanoparticles becomes available, machine learning and data mining would become a powerful aid in the design of nanoparticles for biomedical applications. There is however the challenge of great heterogeneity in nanoparticles, which will make these discoveries more challenging than for traditional small molecule drug design. PMID- 27282233 TI - Real-time seizure prediction using RLS filtering and interpolated histogram feature based on hybrid optimization algorithm of Bayesian classifier and Hunting search. AB - BACKGROUND AND OBJECTIVES: Epileptic seizure prediction using EEG signal analysis is an important application for drug therapy and pediatric patient monitoring. Time series estimation to obtain the future samples of EEG signal has vital role for detecting seizure attack. In this paper, a novel density-based real-time seizure prediction algorithm based on a trained offline seizure detection algorithm is proposed. METHODS: In the offline seizure detection procedure, after signal preprocessing, histogram-based statistical features are extracted from signal probability distribution. By defining a deterministic polynomial model on the normalized histogram, a novel syntactic feature that is named Interpolated Histogram Feature (IHF) is proposed. Moreover, with this feature, Seizure Distribution Model (SDM) as a descriptor of the seizure and non-seizure signals is presented. By using a novel hybrid optimization algorithm based on Bayesian classifier and Hunting Search (HuS) algorithm, the optimal features are selected. To detect the seizure attacks in the online mode, a Multi-Layer Perceptron (MLP) classifier is trained with the optimal features in the offline procedure. For online prediction, the enhanced Recursive Least Square (RLS) filter is applied to estimate sample-by-sample of the EEG signal. Also, a density-based signal tracking scenario is introduced to update and tune the parameters of RLS filtering algorithm. RESULTS: Our prediction algorithm is evaluated on 104 hours of EEG signals recorded from 23 pediatric patients. Our online signal prediction algorithm provides the accuracy rate of 86.56% and precision rate of 86.53% simultaneously using the trained MLP classifier from the offline mode. The recall rate of seizure prediction is 97.27% and the false prediction rate of 0.00215 per hour is achieved as well. Ultimately, the future samples of EEG signal are estimated, and the time of seizure signal prediction is also converged to 6.64 seconds. CONCLUSION: In our proposed real-time algorithm, by implementing a density-based signal tracking scenario, the future samples of signal with suitable time is predicted and the seizure is detected based on the optimal features from the IHF and histogram-based statistical features with acceptable performance. PMID- 27282232 TI - Cloud-based BP system integrated with CPOE improves self-management of the hypertensive patients: A randomized controlled trial. AB - BACKGROUND: Less than 50% of patients with hypertensive disease manage to maintain their blood pressure (BP) within normal levels. OBJECTIVE: The aim of this study is to evaluate whether cloud BP system integrated with computerized physician order entry (CPOE) can improve BP management as compared with traditional care. METHODS: A randomized controlled trial done on a random sample of 382 adults recruited from 786 patients who had been diagnosed with hypertension and receiving treatment for hypertension in two district hospitals in the north of Taiwan. Physicians had access to cloud BP data from CPOE. Neither patients nor physicians were blinded to group assignment. The study was conducted over a period of seven months. RESULTS: At baseline, the enrollees were 50% male with a mean (SD) age of 58.18 (10.83) years. The mean sitting BP of both arms was no different. The proportion of patients with BP control at two, four and six months was significantly greater in the intervention group than in the control group. The average capture rates of blood pressure in the intervention group were also significantly higher than the control group in all three check-points. CONCLUSIONS: Cloud-based BP system integrated with CPOE at the point of care achieved better BP control compared to traditional care. This system does not require any technical skills and is therefore suitable for every age group. The praise and assurance to the patients from the physicians after reviewing the Cloud BP records positively reinforced both BP measuring and medication adherence behaviors. PMID- 27282234 TI - Iterative fuzzy segmentation for an accurate delimitation of the breast region. AB - In mammographic images, extracting different anatomical structures and tissues types is a critical requirement for the breast cancer diagnosis. For instance, separating breast and background regions increases the accuracy and efficiency of mammographic processing algorithms. In this paper, we propose a new region-based method to properly segment breast and background regions in mammographic images. These regions are estimated by an Iterative Fuzzy Breast Segmentation method (IFBS). Based on the Fuzzy C-Means (FCM) algorithm, IFBS method iteratively increases the precision of an initially extracted breast region. This proposal is evaluated using the MIAS database. Experimental results show high accuracy and reliability in breast extraction when compared with Ground-Truth (GT) images. PMID- 27282235 TI - 3D active surfaces for liver segmentation in multisequence MRI images. AB - Biopsies for diagnosis can sometimes be replaced by non-invasive techniques such as CT and MRI. Surgeons require accurate and efficient methods that allow proper segmentation of the organs in order to ensure the most reliable intervention planning. Automated liver segmentation is a difficult and open problem where CT has been more widely explored than MRI. MRI liver segmentation represents a challenge due to the presence of characteristic artifacts, such as partial volumes, noise and low contrast. In this paper, we present a novel method for multichannel MRI automatic liver segmentation. The proposed method consists of the minimization of a 3D active surface by means of the dual approach to the variational formulation of the underlying problem. This active surface evolves over a probability map that is based on a new compact descriptor comprising spatial and multisequence information which is further modeled by means of a liver statistical model. This proposed 3D active surface approach naturally integrates volumetric regularization in the statistical model. The advantages of the compact visual descriptor together with the proposed approach result in a fast and accurate 3D segmentation method. The method was tested on 18 healthy liver studies and results were compared to a gold standard made by expert radiologists. Comparisons with other state-of-the-art approaches are provided by means of nine well established quality metrics. The obtained results improve these methodologies, achieving a Dice Similarity Coefficient of 98.59. PMID- 27282236 TI - Efficient patient modeling for visuo-haptic VR simulation using a generic patient atlas. AB - BACKGROUND AND OBJECTIVE: This work presents a new time-saving virtual patient modeling system by way of example for an existing visuo-haptic training and planning virtual reality (VR) system for percutaneous transhepatic cholangio drainage (PTCD). METHODS: Our modeling process is based on a generic patient atlas to start with. It is defined by organ-specific optimized models, method modules and parameters, i.e. mainly individual segmentation masks, transfer functions to fill the gaps between the masks and intensity image data. In this contribution, we show how generic patient atlases can be generalized to new patient data. The methodology consists of patient-specific, locally-adaptive transfer functions and dedicated modeling methods such as multi-atlas segmentation, vessel filtering and spline-modeling. RESULTS: Our full image volume segmentation algorithm yields median DICE coefficients of 0.98, 0.93, 0.82, 0.74, 0.51 and 0.48 regarding soft-tissue, liver, bone, skin, blood and bile vessels for ten test patients and three selected reference patients. Compared to standard slice-wise manual contouring time saving is remarkable. CONCLUSIONS: Our segmentation process shows out efficiency and robustness for upper abdominal puncture simulation systems. This marks a significant step toward establishing patient-specific training and hands-on planning systems in a clinical environment. PMID- 27282237 TI - Three-dimensional reconstruction of trachea using computed tomography imaging as therapy for tracheal stenosis in infants. AB - BACKGROUND AND OBJECTIVE: In this study, we aim to develop a system that uses computed tomography (CT) imaging for three-dimensional (3D) reconstruction of the trachea as therapy for tracheal stenosis in infants, and further calculate the cross-sectional area and volume, assisting doctors in clinical diagnosis. METHODS: We first used image processing, calculating the cross-sectional area and volume. We used the improved median filter for image processing and designed the system for capturing the cross-sectional area of endotracheal tube. We then established 3D reconstruction images with isosurface extraction technology and calculated the cross-sectional area and volume. Medical indicator data analysis was performed. RESULTS: The median filter developed in this study performed better in filtering speckle noise compared to traditional filtering methods. Furthermore, the median filter can keep fine texture feature, so that the subsequent contour selection and 3D reconstructed volume are more accurate. We also proposed new medical grading indexes according to tracheal obstruction volume ratio to assist doctors with the diagnosis and provide recommendations on treatment. Seventeen samples were examined in this study. Four sections of each sample are reviewed. Sixty-eight sections were used for validation, and the overall accuracy is very reliable. CONCLUSIONS: Using image processing we obtained tracheal CT images before 3D reconstruction and calculated the cross sectional area and volume of the trachea. New medical indicators are proposed according to the location and severity of stenosis to assist doctors with diagnosis. PMID- 27282238 TI - Dynamic relaxation in algebraic reconstruction technique (ART) for breast tomosynthesis imaging. AB - BACKGROUND AND OBJECTIVES: A major challenge in Digital Breast Tomosynthesis (DBT) is handling image noise since the 3D reconstructed images are obtained from low dose projections and limited angular range. The use of the iterative reconstruction algorithm Algebraic Reconstruction Technique (ART) in clinical context depends on two key factors: the number of iterations needed (time consuming) and the image noise after iterations. Both factors depend highly on a relaxation coefficient (lambda), which may give rise to slow or noisy reconstructions, when a single lambda value is considered for the entire iterative process. The aim of this work is to present a new implementation for the ART that takes into account a dynamic mode to calculate lambda in DBT image reconstruction. METHODS: A set of initial reconstructions of real phantom data was done using constant lambda values. The results were used to choose, for each iteration, the suitable lambda value, taking into account the image noise level and the convergence speed. A methodology to optimize lambda automatically during the image reconstruction was proposed. RESULTS: Results showed we can dynamically choose lambda values in such a way that the time needed to reconstruct the images can be significantly reduced (up to 70%) while achieving similar image quality. These results were confirmed with one clinical dataset. CONCLUSIONS: With simple methodology we were able to dynamically choose lambda in DBT image reconstruction with ART, allowing a shorter image reconstruction time without increasing image noise. PMID- 27282239 TI - gVARVI: A graphical software tool for the acquisition of the heart rate in response to external stimuli. AB - BACKGROUND AND OBJECTIVE: At present, tools capable of acquiring heart rate data can be found both in commercial and research fields. However, these tools do not allow users to manage experiments comprising sequences of activities or to store the information needed to perform heart rate variability analysis across different activities. One exception is VARVI, a simple software tool developed previously in our research group that does not have a graphical user interface and it works only with visual stimuli. In this paper, we present gVARVI, a software tool aimed at obtaining heart rate data signals while the user is either receiving a sequence of external stimuli or performing a sequence of actions (an activity). METHODS: gVARVI is an open source application developed in Python programming language. It can acquire heart rate data by means of a wireless chest strap using either Bluetooth or ANT+ protocols. Users can define activities of different types (video, sounds, pictures or keyboard controlled actions) which will associate contextual information to the heart rate data. gVARVI allows users to preview this data or to store it to be used for heart rate variability studies. Our tool was validated by 15 researchers, who worked with the application and filled in a usability questionnaire. RESULTS: The outcome of the usability test was satisfactory, giving a mean score of 4.75 in a 1-5 scale (1 - strongly disagree, 5 - strongly agree). Participants also contributed with valuable comments, which we used to include new features in the last version of our tool. CONCLUSIONS: gVARVI is an open source tool that offers new possibilities to both physicians and clinicians to perform heart rate variability studies. It allows users to acquire heart rate data including information on the activity performed by subjects while recording. In this paper, we describe all the functionalities included in gVARVI, and a complete example of use is provided. PMID- 27282240 TI - Editorial. PMID- 27282241 TI - The behaviour of green tea catechins in a full-fat milk system under conditions mimicking the cheesemaking process. AB - Due to their well-known health benefits, green tea catechins have received recent attention as natural additives in foods such as dairy products. However, they may present some irreversible associations with milk components (e.g. protein and milk fat globules). To investigate the behaviour of two important green tea catechins, (+)-catechin (C) and (-)-epigallocatechin gallate (EGCG), in a standard whole milk system under the conditions of cheesemaking, 250 and 500 ppm of each catechin were added to whole milk (3.3% fat). Although both C and EGCG at either concentration increased both total phenolic content and total antioxidant capacity of the subnatants obtained from the milk system, there was a less linear increase when the concentration of the catechins was doubled, whereas C or EGCG were recovered (measured by HPLC) differently. Overall, these results suggest a degree of associations between green tea catechins with milk proteins and milk fat. PMID- 27282242 TI - Influence of static electric field on cognition in mice. AB - With the rapid development of high voltage direct current transmission, the possibility of health effects associated with static electric field (SEF) has caused wide public concern. To examine the effects of long-lasting, full-body exposure to SEF on cognition, Institute of Cancer Research mice were exposed to SEF for 35 d. The intensities of SEF in experimental group I (EG-I), experimental group II (EG-II) and control group (CG) were 2.30~15.40 kV/m, 9.20~21.85 kV/m and 0 kV/m, respectively. The performance in learning and memory of mice were tested by Morris water maze (MWM) on days 2~6, 16~20 and 30~34 during the exposure period. The concentrations of hippocampal amino acid neurotransmitters were evaluated on days 7, 21 and 35. Results showed that the latency in the MWM test had no significant difference among the EG-I, EG-II and CG (P > 0.05) during the exposure period. The percentage of time spent in the target quadrant was significantly decreased in the EG-II on day 34 during the exposure period (P < 0.05), whereas the percentage of time spent in the opposite quadrant increased markedly (P < 0.01). The glutamate and gamma-aminobutyric acid concentrations showed no significant differences among the EG-I, EG-II and CG (P > 0.05) during the exposure period. These results indicated that long-lasting, full-body exposure to SEF with certain intensity would not cause significant influence on learning ability, but it might associate with memory impairment of receptors. Meanwhile, this effect of memory impairment was dose-dependent and not causally linked to the glutamate and gamma-aminobutyric acid levels in the hippocampus. PMID- 27282243 TI - Shadows of Beauty - Prevalence of Body Dysmorphic Concerns in Germany is Increasing: Data from Two Representative Samples from 2002 and 2013. AB - Body dysmorphic disorder (BDD) is a psychosomatic disease associated with reduced quality of life and suicidal ideations. Increasing attention to beauty and the development of beauty industries lead to the hypothesis that BDD is increasing. The aim of this study was to test this hypothesis in two representative samples of Germans, assessed in 2002 and 2013. In 2002, n = 2,066 and in 2013, n = 2,508 Germans were asked to fill in the Dysmorphic Concern Questionnaire (DCQ), which assesses dysmorphic concerns. Subclinical and clinical dysmorphic concerns increased from 2002 to 2013 (subclinical from 0.5% to 2.6%, OR = 5.16 (CI95% = 2.64; 10.06); clinical from 0.5% to 1.0%, OR = 2.20 (CI95% = 1.03; 4.73). Women reported more dysmorphic concerns than men, with rates of 0.7% subclinical and 0.8 clinical BDD in women and 0.3% subclinical and 0.1% clinical BDD in men in 2002. In 2013, 2.8% subclinical and 1.2% clinical BDD were found in women and 2.4% subclinical and 0.8% clinical BDD in men. Further studies should assess predictors for developing a BDD and evaluate factors determining the efficacy of disease-specific psychotherapeutic and psychotropic drug treatments. PMID- 27282244 TI - Epidemiology and pathogenesis of diffuse obstructive coronary artery disease: the role of arterial stiffness, shear stress, monocyte subsets and circulating microparticles. AB - Despite falling age-adjusted mortality rates coronary artery disease (CAD) remains the leading cause of death worldwide. Advanced diffuse CAD is becoming an important entity of modern cardiology as more patients with historical revascularisation no longer have suitable anatomy for additional procedures. Advances in the treatment of diffuse obstructive CAD are hampered by a poor understanding of its development. Although the likelihood of developing clinically significant (obstructive) CAD is linked to traditional risk factors, the morphology of obstructive CAD among individuals is highly variable - some patients have diffuse stenotic disease, while others have a focal stenosis. This is challenging to explain in mechanistic terms as vascular endothelium is equally exposed to injury stimulants. Patients with diffuse disease are at high risk of adverse outcomes, particularly if unsuitable for revascularisation. We searched multiple electronic databases (MEDLINE, EMBASE and the Cochrane Database) and reviewed the epidemiology, pathogenesis and prognosis relating to advanced diffuse CAD with particular focus on the role of endothelial shear stress, large artery stiffness, monocyte subsets and circulating microparticles. Key messages Although traditional CAD risk factors correlate strongly with disease severity, significant individual variation in disease morphology exists. Advanced, diffuse CAD is difficult to treat effectively and can significantly impair quality of life and increases mortality. The pathophysiology associated with the progression of CAD is the result of complex maladaptive interaction between the endothelium, cells of the immune system and patterns of blood flow. PMID- 27282245 TI - Association of psychological, cognitive, and functional variables with self reported executive functioning in a sample of nondemented community-dwelling older adults. AB - Subjective executive functioning (EF) measures provide valuable information about real-world difficulties, although it is unclear what variables actually associate with subjective EF scores. We investigated subjective EF in 245 nondemented, community-dwelling older adults (aged 70 and above) from the Einstein Aging Study. Partial correlational analyses controlling for age were performed between the nine Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) clinical scales and objective EF tests, self-reported mood and personality, and informant-reported activities of daily living. The significance level was set at p < .006 for all analyses (two-tailed). Most notably, higher worry/oversensitivity, physiological anxiety, and fear of aging were significantly associated with increased EF difficulties on all nine BRIEF-A scales. Additionally, increased EF difficulties on five or more BRIEF-A scales were significantly associated with lower conscientiousness, higher neuroticism, and higher depressive symptom scores. The only objective neuropsychological test that significantly correlated with increased EF difficulties (on four BRIEF-A scales) was a measure of practical judgment. Overall, results indicate that interpretation of subjective EF scores must account for self-report of mood and personality. Moreover, the BRIEF-A only minimally taps objective EF as measured by performance-based measures. We discuss the theoretical and practical implications of these findings. PMID- 27282246 TI - Lysophosphatidylcholine plays critical role in allergic airway disease manifestation. AB - Phospholipase A2 (sPLA2), pivotal for allergic and inflammatory response, hydrolyses phosphatidylcholine (PC) to lysophosphatidylcholine (LPC). In present study, the role of LPC in allergic airway disease manifestation was studied using mouse model. Balb/c mice were immunized using cockroach extract (CE) and LPC release was blocked by sPLA2 inhibitor. Airway hyperresponse (AHR), lung histology, total and differential leukocyte count (TLC&DLC), Th2 type cytokines, sPLA2 activity and LPC levels in bronchoalveolar lavage fluid (BALF) were measured. Exogenous LPC was given to the mice with or without CE sensitization, to demonstrate its role in allergic airway disease manifestation. Anti-CD1d antibody was given to study the involvement of natural killer T (NKT) cells in LPC induced response. AHR, lung-inflammation, TLC, DLC, Th2 type cytokines, sPLA2 activity and LPC levels were increased on CE challenge. sPLA2 activity and LPC release was blocked by sPLA2-inhibitor, which decreased AHR, and inflammatory parameters. Exogenous LPC with or without CE sensitization increased above parameters. CE challenge or LPC exposure increased LY49C(+)TCRbeta(+) NKT cells in BALF and spleen, which was reduced by anti-CD1d antibody, accompanied with reduction in AHR and allergic airway inflammation parameters. Conclusively, LPC induces allergic airway disease manifestation and it does so probably via CD1d restricted LY49C(+)TCRbeta(+) NKT cells. PMID- 27282247 TI - Associative-memory representations emerge as shared spatial patterns of theta activity spanning the primate temporal cortex. AB - Highly localized neuronal spikes in primate temporal cortex can encode associative memory; however, whether memory formation involves area-wide reorganization of ensemble activity, which often accompanies rhythmicity, or just local microcircuit-level plasticity, remains elusive. Using high-density electrocorticography, we capture local-field potentials spanning the monkey temporal lobes, and show that the visual pair-association (PA) memory is encoded in spatial patterns of theta activity in areas TE, 36, and, partially, in the parahippocampal cortex, but not in the entorhinal cortex. The theta patterns elicited by learned paired associates are distinct between pairs, but similar within pairs. This pattern similarity, emerging through novel PA learning, allows a machine-learning decoder trained on theta patterns elicited by a particular visual item to correctly predict the identity of those elicited by its paired associate. Our results suggest that the formation and sharing of widespread cortical theta patterns via learning-induced reorganization are involved in the mechanisms of associative memory representation. PMID- 27282248 TI - Transient ECM protease activity promotes synaptic plasticity. AB - Activity-dependent proteolysis at a synapse has been recognized as a pivotal factor in controlling dynamic changes in dendritic spine shape and function; however, excessive proteolytic activity is detrimental to the cells. The exact mechanism of control of these seemingly contradictory outcomes of protease activity remains unknown. Here, we reveal that dendritic spine maturation is strictly controlled by the proteolytic activity, and its inhibition by the endogenous inhibitor (Tissue inhibitor of matrix metalloproteinases-1 - TIMP-1). Excessive proteolytic activity impairs long-term potentiation of the synaptic efficacy (LTP), and this impairment could be rescued by inhibition of protease activity. Moreover LTP is altered persistently when the ability of TIMP-1 to inhibit protease activity is abrogated, further demonstrating the role of such inhibition in the promotion of synaptic plasticity under well-defined conditions. We also show that dendritic spine maturation involves an intermediate formation of elongated spines, followed by their conversion into mushroom shape. The formation of mushroom-shaped spines is accompanied by increase in AMPA/NMDA ratio of glutamate receptors. Altogether, our results identify inhibition of protease activity as a critical regulatory mechanism for dendritic spines maturation. PMID- 27282251 TI - Upregulation of p27 cyclin-dependent kinase inhibitor and a C-terminus truncated form of p27 contributes to G1 phase arrest. AB - Potent anti-cancer compounds FR901464 and its methyl-ketal derivative spliceostatin A (SSA) inhibit cell cycle progression at G1 and G2/M phases. These compounds bind to the spliceosome and inhibit the splicing reaction. However, the molecular mechanism underlying G1 arrest after SSA treatment remains unknown. In this study, we found that ~90% of SSA-treated cells arrested at G1 phase after cell cycle synchronization. SSA treatment caused upregulation of the p27 cyclin dependent kinase inhibitor both at mRNA and protein levels. In addition to p27, we observed expression of p27*, a C-terminal truncated form of p27 that is translated from CDKN1B (p27) pre-mRNA accumulated after splicing inhibition. Overexpression of p27 or p27* inhibited the exit from G1 phase after a double thymidine block. Conversely, knocking down of p27 by siRNA partially suppressed the G1 phase arrest caused by SSA treatment. There results suggest that G1 arrest in SSA-treated cells is caused, at least in part, by upregulation of p27 and p27*. PMID- 27282249 TI - Neutrophils in cancer: neutral no more. AB - Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. PMID- 27282253 TI - Commentary on: 'Age, not therapy intensity, determines outcomes of adults with acute myeloid leukemia'. PMID- 27282252 TI - Physical, chemical and kinetic factors affecting prion infectivity. AB - The mouse-adapted scrapie prion strain RML is one of the most widely used in prion research. The introduction of a cell culture-based assay of RML prions, the scrapie cell assay (SCA) allows more rapid and precise prion titration. A semi automated version of this assay (ASCA) was applied to explore a range of conditions that might influence the infectivity and properties of RML prions. These include resistance to freeze-thaw procedures; stability to endogenous proteases in brain homogenate despite prolonged exposure to varying temperatures; distribution of infective material between pellet and supernatant after centrifugation, the effect of reducing agents and the influence of detergent additives on the efficiency of infection. Apparent infectivity is increased significantly by interaction with cationic detergents. Importantly, we have also elucidated the relationship between the duration of exposure of cells to RML prions and the transmission of infection. We established that the infection process following contact of cells with RML prions is rapid and followed an exponential time course, implying a single rate-limiting process. PMID- 27282250 TI - RNA splicing factors as oncoproteins and tumour suppressors. AB - The recent genomic characterization of cancers has revealed recurrent somatic point mutations and copy number changes affecting genes encoding RNA splicing factors. Initial studies of these 'spliceosomal mutations' suggest that the proteins bearing these mutations exhibit altered splice site and/or exon recognition preferences relative to their wild-type counterparts, resulting in cancer-specific mis-splicing. Such changes in the splicing machinery may create novel vulnerabilities in cancer cells that can be therapeutically exploited using compounds that can influence the splicing process. Further studies to dissect the biochemical, genomic and biological effects of spliceosomal mutations are crucial for the development of cancer therapies targeted at these mutations. PMID- 27282254 TI - Genomic disruption of the histone methyltransferase SETD2 in chronic lymphocytic leukaemia. AB - Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis. With next generation sequencing we detected mutations of SETD2 in an additional 3.8% of patients (23/602). In most cases, SETD2 deletions or mutations were often observed as a clonal event and always as a mono-allelic lesion, leading to reduced mRNA expression in SETD2-disrupted cases. Patients with SETD2 abnormalities and wild-type TP53 and ATM from five clinical trials employing chemotherapy or chemo-immunotherapy had reduced progression-free and overall survival compared with cases wild type for all three genes. Consistent with its postulated role as a tumour suppressor, our data highlight SETD2 aberration as a recurrent, early loss-of-function event in CLL pathobiology linked to aggressive disease. PMID- 27282256 TI - The T-type calcium channel antagonist Z944 rescues impairments in crossmodal and visual recognition memory in Genetic Absence Epilepsy Rats from Strasbourg. AB - Childhood absence epilepsy (CAE) is often comorbid with behavioral and cognitive symptoms, including impaired visual memory. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is an animal model closely resembling CAE; however, cognition in GAERS is poorly understood. Crossmodal object recognition (CMOR) is a recently developed memory task that examines not only purely visual and tactile memory, but also requires rodents to integrate sensory information about objects gained from tactile exploration to enable visual recognition. Both the visual and crossmodal variations of the CMOR task rely on the perirhinal cortex, an area with dense expression of T-type calcium channels. GAERS express a gain-in function missense mutation in the Cav3.2 T-type calcium channel gene. Therefore, we tested whether the T-type calcium channel blocker Z944 dose dependently (1, 3, 10mg/kg; i.p.) altered CMOR memory in GAERS compared to the non-epileptic control (NEC) strain. GAERS demonstrated recognition memory deficits in the visual and crossmodal variations of the CMOR task that were reversed by the highest dose of Z944. Electroencephalogram recordings determined that deficits in CMOR memory in GAERS were not the result of seizures during task performance. In contrast, NEC showed a decrease in CMOR memory following Z944 treatment. These findings suggest that T-type calcium channels mediate CMOR in both the GAERS and NEC strains. Future research into the therapeutic potential of T-type calcium channel regulation may be particularly fruitful for the treatment of CAE and other disorders characterized by visual memory deficits. PMID- 27282257 TI - Experiences With a Self-Reported Mobile Phone-Based System Among Patients With Colorectal Cancer: A Qualitative Study. AB - BACKGROUND: In cancer care, mobile phone-based systems are becoming more widely used in the assessment, monitoring, and management of side effects. OBJECTIVE: To explore the experiences of patients with colorectal cancer on using a mobile phone-based system for reporting neurotoxic side effects. METHODS: Eleven patients were interviewed (ages 44-68 years). A semistructured interview guide was used to perform telephone interviews. The interviews were transcribed verbatim and analyzed with qualitative content analysis. RESULTS: The patients' experiences of using a mobile phone-based system were identified and constructed as: "being involved," "pacing oneself," and "managing the questions." "Being involved" refers to their individual feelings. Patients were participating in their own care by being observant of the side effects they were experiencing. They were aware that the answers they gave were monitored in real time and taken into account by health care professionals when planning further treatment. "Pacing oneself" describes how the patients can have an impact on the time and place they choose to answer the questions. Answering the questionnaire was easy, and despite the substantial number of questions, it was quickly completed. "Managing the questions" pointed out that the patients needed to be observant because of the construction of the questions. They could not routinely answer all the questions. Patients understood that side effects can vary during the cycles of treatment and need to be assessed repeatedly during treatment. CONCLUSIONS: This mobile phone-based system reinforced the patients' feeling of involvement in their own care. The patients were comfortable with the technology and appreciated that the system was not time consuming. PMID- 27282258 TI - Barrier inhomogeneities limited current and 1/f noise transport in GaN based nanoscale Schottky barrier diodes. AB - The electrical behaviour of Schottky barrier diodes realized on vertically standing individual GaN nanorods and array of nanorods is investigated. The Schottky diodes on individual nanorod show highest barrier height in comparison with large area diodes on nanorods array and epitaxial film which is in contrast with previously published work. The discrepancy between the electrical behaviour of nanoscale Schottky diodes and large area diodes is explained using cathodoluminescence measurements, surface potential analysis using Kelvin probe force microscopy and 1ow frequency noise measurements. The noise measurements on large area diodes on nanorods array and epitaxial film suggest the presence of barrier inhomogeneities at the metal/semiconductor interface which deviate the noise spectra from Lorentzian to 1/f type. These barrier inhomogeneities in large area diodes resulted in reduced barrier height whereas due to the limited role of barrier inhomogeneities in individual nanorod based Schottky diode, a higher barrier height is obtained. PMID- 27282259 TI - Corrigendum: Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice. PMID- 27282255 TI - Substitution scanning identifies a novel, catalytically active ibrutinib resistant BTK cysteine 481 to threonine (C481T) variant. AB - Irreversible Bruton tyrosine kinase (BTK) inhibitors, ibrutinib and acalabrutinib have demonstrated remarkable clinical responses in multiple B-cell malignancies. Acquired resistance has been identified in a sub-population of patients in which mutations affecting BTK predominantly substitute cysteine 481 in the kinase domain for catalytically active serine, thereby ablating covalent binding of inhibitors. Activating substitutions in the BTK substrate phospholipase Cgamma2 (PLCgamma2) instead confers resistance independent of BTK. Herein, we generated all six possible amino acid substitutions due to single nucleotide alterations for the cysteine 481 codon, in addition to threonine, requiring two nucleotide substitutions, and performed functional analysis. Replacement by arginine, phenylalanine, tryptophan or tyrosine completely inactivated the catalytic activity, whereas substitution with glycine caused severe impairment. BTK with threonine replacement was catalytically active, similar to substitution with serine. We identify three potential ibrutinib resistance scenarios for cysteine 481 replacement: (1) Serine, being catalytically active and therefore predominating among patients. (2) Threonine, also being catalytically active, but predicted to be scarce, because two nucleotide changes are needed. (3) As BTK variants replaced with other residues are catalytically inactive, they presumably need compensatory mutations, therefore being very scarce. Glycine and tryptophan variants were not yet reported but likely also provide resistance. PMID- 27282260 TI - Predictive Value of Antiviral Effects in the Development of Hepatocellular Carcinoma in the General Korean Population with Chronic Hepatitis B. AB - Background/Aims: The benefit of oral antiviral therapy in preventing hepatocellular carcinoma (HCC) in the general population is not well understood. We used a novel prediction method to estimate the risk of HCC in the Korean population based on various treatment guidelines. Methods: The 5-year risk of HCC following antiviral therapy was calculated using an HCC risk prediction model. A virtual cohort that represented Koreans (>40 years old) with chronic hepatitis B virus (HBV) infection was established using the fifth National Health and Nutrition Examination Survey. The antiviral indications tested were the Korean National Health Insurance (NHI) and European Association for the Study of the Liver (EASL) guidelines as well as a new extended indication (serum HBV DNA >2,000 IU/mL regardless of serum aminotransferase level). Results: A total of 993,872 subjects were infected with HBV in the general Korean population. Over a 5-year period, 2,725 HCC cases were predicted per 100,000 persons (0.55%/yr). When the cohort was treated based on the Korean NHI, the EASL, and the newly extended indications, HCC risks decreased to 2,531 (-7.1%), 2,089 (-23.3%), and 1,122 (-58.8%) cases per 100,000 persons, respectively (p<0.0001). Conclusions: Simulated risk prediction suggests that extending of oral antiviral indication may reduce the HCC risk in the general population. PMID- 27282261 TI - Limited Effect of Rebamipide in Addition to Proton Pump Inhibitor (PPI) in the Treatment of Post-Endoscopic Submucosal Dissection Gastric Ulcers: A Randomized Controlled Trial Comparing PPI Plus Rebamipide Combination Therapy with PPI Monotherapy. AB - Background/Aims: The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods: In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results: The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions: Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435). PMID- 27282262 TI - Performance of the Fecal Immunochemical Test for Colorectal Cancer Screening Using Different Stool-Collection Devices: Preliminary Results from a Randomized Controlled Trial. AB - Background/Aims: We are in the process of conducting a randomized trial to determine whether compliance with the fecal immunochemical test (FIT) for colorectal cancer screening differs according to the stool-collection method. This study was an interim analysis of the performance of two stool-collection devices (sampling bottle vs conventional container). Methods: In total, 1,701 individuals (age range, 50 to 74 years) were randomized into the sampling bottle group (intervention arm) or the conventional container group (control arm). In both groups, we evaluated the FIT positivity rate, the positive predictive value for advanced neoplasia, and the detection rate for advanced neoplasia. Results: The FIT positivity rates were 4.1% for the sampling bottles and 2.0% for the conventional containers; these values were significantly different. The positive predictive values for advanced neoplasia in the sampling bottles and conventional containers were 11.1% (95% confidence interval [CI], -3.4 to 25.6) and 12.0% (95% CI, -0.7 to 24.7), respectively. The detection rates for advanced neoplasia in the sampling bottles and conventional containers were 4.5 per 1,000 persons (95% CI, 2.0 to 11.0) and 2.4 per 1,000 persons (95% CI, 0.0 to 5.0), respectively. Conclusions: The impact of these findings on FIT screening performance was unclear in this interim analysis. This impact should therefore be evaluated in the final analysis following the final enrollment period. PMID- 27282263 TI - Antral or Pyloric Deformity Is a Risk Factor for the Development of Postendoscopic Submucosal Dissection Pyloric Strictures. AB - BACKGROUND/AIMS: Surgeons must be aware of risk factors for strictures before performing endoscopic submucosal dissection (ESD), to enable early interventions to prevent severe strictures. METHODS: This study was a single-center retrospective study. We reviewed the clinical data of patients who has undergone gastric ESD from January 2007 to December 2012. RESULTS: Among the 3,819 patients who had undergone gastric ESD, 11 patients (7.2%) developed pyloric strictures and received successful endoscopic balloon dilation. Significant differences were noted between the patients without and with post-ESD strictures for pretreatment of antral or pyloric deformities (46.4% vs 81.8%), the proportion of extension to the lumen circumference (>3/4, 9.4% vs 54.5%), the longitudinal extent of mucosal defects (27.9+/-10.1 mm vs 51.5+/-10.8 mm), and post-ESD bleeding (2.9% vs 27.3%). Multivariate analysis revealed that pretreatment antral or pyloric deformities (odds ratio [OR], 30.53; 95% confidence interval [CI], 1.476 to 631.565; p=0.027), larger longitudinal extent of mucosal defects (OR, 1.20; 95% CI, 1.074 to 1.340; p=0.001), and circumferential extension of >=3/4 (OR, 13.69; 95% CI, 1.583 to 118.387; p=0.017) were independent risk factors for post-ESD stricture. CONCLUSIONS: Antral or pyloric deformities, sub-circumferential resection over more than 75% of the circumference and greater longitudinal extent of mucosal defects are independent risk factors for post-ESD stricture. PMID- 27282264 TI - Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma. AB - Background/Aims: Antiviral therapy is a key component in the management of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. However, whether the potent drug entecavir is more effective than a less potent drug, such as lamivudine, in HBV-related HCC is not clear. Methods: A retrospective cohort of 451 newly diagnosed, HBV-related HCC patients without antiviral therapy at diagnosis, who started antiviral therapy with either entecavir (n=249) or lamivudine (n=202), were enrolled. Results: The median survival was longer for the entecavir group than for the lamivudine group, and lamivudine use (vs entecavir) was an independent factor for mortality (hazard ratio [HR], 1.49; p=0.002). Lamivudine use (vs entecavir) was an independent risk factor for new onset hepatic decompensation (HR, 1.67; p=0.010) in 318 patients without previous hepatic decompensation, and it was also an independent risk factor for recurrence after curative therapy (HR, 1.84; p=0.002) in 117 patients who received curative therapy. The findings were similar in a propensity score-matched cohort. Conclusions: Overall survival, decompensation-free survival, and recurrence-free survival were better in the entecavir-treated patients than in the lamivudine treated-patients, indicating that the potent antiviral drug should be the preferred choice in HBV-related HCC patients. PMID- 27282265 TI - The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study. AB - Background/Aims: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. Methods: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. Results: The mean decreases in the total symptom score at 4 weeks were estimated to be -18.1+/-13.8 in the combination therapy group and -15.1+/-11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were -8.4+/-6.6 in the combination therapy group and -6.8+/ 5.9 in the monotherapy group (p=0.009). Conclusions: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy. PMID- 27282266 TI - NADPH Oxidase 1 and NADPH Oxidase 4 Have Opposite Prognostic Effects for Patients with Hepatocellular Carcinoma after Hepatectomy. AB - BACKGROUND/AIMS: Nicotinamide adenine dinucleotide phosphate oxidase (NOX) mediated reactive oxygen species contribute to various liver diseases, including hepatocellular carcinoma (HCC). Uncertainties remain regarding the prognostic relevance of NOX1 and NOX4 protein expression in HCC. METHODS: NOX1 and NOX4 protein expression was examined by using immunohistochemistry in tumor tissue from 227 HCC patients who underwent hepatectomy. RESULTS: High immunoreactivity for NOX1 was observed in 197 (86.8%) of the 227 HCC cases and low immunoreactivity for NOX4 in 112 (49.3%). NOX1 and NOX4 proteins had opposite prognostic effects. High NOX1 expression was an independent predictor of both shorter recurrence-free survival (RFS) (p<0.01) and shorter overall survival (OS) (p=0.01). Low NOX4 expression was an independent predictor of both shorter RFS (p<0.01) and shorter OS (p=0.01). Subgroup analysis showed that, among patients with normal alpha-fetoprotein levels, patients with tumor size <=5.0 cm and patients in Barcelona Clinic Liver Cancer stage A, high NOX1 expression had unfavorable effects on RFS, whereas low NOX4 expression had unfavorable effects on both RFS and OS. CONCLUSIONS: These findings demonstrated that NOX1 and NOX4 protein expression had opposite prognostic effects for HCC patients. Moreover, both proteins had prognostic value in HCC patients with normal alpha-fetoprotein levels or with early-stage HCC. PMID- 27282267 TI - Quality of Life after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Prospective Multicenter Cohort Study. AB - Background/Aims: Endoscopic submucosal dissection (ESD) has been an established treatment for indicated early gastric cancer (EGC) without deterioration of quality of life (QOL) compared with surgical resection. The aim of this study was to evaluate long-term QOL in patients undergoing ESD for EGC. Methods: Patients scheduled to undergo curative ESD for EGC were prospectively enrolled from 12 institutions between May 2010 and December 2011. Assessments of QOL with Korean versions of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and a gastric cancer-specific questionnaire (STO22) were performed at baseline and at 7 days, 3 months, and 6 months after ESD. Results: A total of 666 subjects were assessed for QLQ-C30 and QLQ-STO22. The mean QLQ-C30 score was 69.5 at baseline, 68.8 at 7 days, 73.1 at 3 months, and 73.2 at 6 months. The global health status on the EORTC QLQ-C30 was significantly improved after 3 and 6 months (p=0.0003 and p<0.0001, respectively). The QLQ-C30 and STO22 scores were not significantly different, or they only slightly deteriorated between before and immediately after ESD, but they were significantly improved after 3 and 6 months (p<0.05). Conclusions: QOL did not deteriorate immediately after ESD, and it improved more significantly at up to 6 months in patients who underwent curative ESD for EGC without significant complications. PMID- 27282268 TI - Antireflux Metal Stent as a First-Line Metal Stent for Distal Malignant Biliary Obstruction: A Pilot Study. AB - Background/Aims: In distal malignant biliary obstruction, an antireflux metal stent (ARMS) with a funnel-shaped valve is effective as a reintervention for metal stent occlusion caused by reflux. This study sought to evaluate the feasibility of this ARMS as a first-line metal stent. Methods: Patients with nonresectable distal malignant biliary obstruction were identified between April and December 2014 at three Japanese tertiary centers. We retrospectively evaluated recurrent biliary obstruction and adverse events after ARMS placement. Results: In total, 20 consecutive patients were included. The most common cause of biliary obstruction was pancreatic cancer (75%). Overall, recurrent biliary obstruction was observed in seven patients (35%), with a median time to recurrent biliary obstruction of 246 days (range, 11 to 246 days). Stent occlusion occurred in five patients (25%), the causes of which were sludge and food impaction in three and two patients, respectively. Stent migration occurred in two patients (10%). The rate of adverse events associated with ARMS was 25%: pancreatitis occurred in three patients, cholecystitis in one and liver abscess in one. No patients experienced nonocclusion cholangitis. Conclusions: The ARMS as a first line biliary drainage procedure was feasible. Because the ARMS did not fully prevent stent dysfunction due to reflux, further investigation is warranted. PMID- 27282269 TI - Helicobacter pylori Eradication Downregulates Cellular Inhibitor of Apoptosis Protein 2 in Gastric Carcinogenesis. AB - Background/Aims: To evaluate the expression of cellular inhibitor of apoptosis protein 2 (cIAP2) during gastric carcinogenesis after Helicobacter pylori (HP) infection and after HP eradication. Methods: We divided non-cancer patients into four groups according to the status of HP infection and atrophic gastritis (AG)/intestinal metaplasia (IM). We compared cIAP2 mRNA expression among these four groups and patients with HP-positive early gastric cancer (EGC) by using real-time polymerase chain reaction (PCR). We evaluated the expression of cIAP2 messenger RNA (mRNA)/protein by using real-time PCR/immunohistochemistry and the degree of apoptosis with a terminal deoxynucleotidyl transferasemediated nick end labeling assay before and 12 months after endoscopic submucosal dissection (ESD) in HP-positive EGC patients, regardless of whether they had undergone eradication therapy. Results: The expression of cIAP2 mRNA was significantly higher in the groups with HP(+), AG/IM(+), and HP-positive EGC than in the control, HP(+), and AG/ IM(-) groups (p<0.005). In the HP eradication group, the expression of cIAP2 mRNA/protein significantly decreased (p=0.006) and apoptosis increased at the 12 month follow-up after ESD. In the HP noneradication group, the aforementioned changes were not found during the same follow-up period. Conclusions: The expression of cIAP2 increased during gastric carcinogenesis after HP infection; HP eradication in the patients who had undergone ESD for EGC reversed overexpression of cIAP2 and suppressed cell apoptosis. PMID- 27282270 TI - National Endoscopy Quality Improvement Program Remains Suboptimal in Korea. AB - BACKGROUND/AIMS: We evaluated the characteristics of the National Cancer Screening Program (NCSP) and opinions regarding the National Endoscopy Quality Improvement Program (NEQIP). METHODS: We surveyed physicians performing esophagogastroduodenoscopy and/or colonoscopy screenings as part of the NCSP via e-mail between July and August in 2015. The 32-item survey instrument included endoscopic capacity, sedation, and reprocessing of endoscopes as well as opinions regarding the NEQIP. RESULTS: A total of 507 respondents were analyzed after the exclusion of 40 incomplete answers. Under the current capacity of the NCSP, the typical waiting time for screening endoscopy was less than 4 weeks in more than 90% of endoscopy units. Performance of endoscopy reprocessing was suboptimal, with 28% of respondents using unapproved disinfectants or not knowing the main ingredient of their disinfectants and 15% to 17% of respondents not following reprocessing protocols. Agreement with the NEQIP was optimal, because only 5.7% of respondents did not agree with NEQIP; however, familiarity with the NEQIP was suboptimal, because only 37.3% of respondents were familiar with the NEQIP criteria. CONCLUSIONS: The NEQIP remains suboptimal in Korea. Given the suboptimal performance of endoscopy reprocessing and low familiarity with the NEQIP, improved quality in endoscopy reprocessing and better understanding of the NEQIP should be emphasized in Korea. PMID- 27282271 TI - Coordinated Hospital-Home Fecal Microbiota Transplantation via Percutaneous Endoscopic Cecostomy for Recurrent Steroid-Dependent Ulcerative Colitis. AB - Since its introduction as an alternative intestinal microbiota alteration approach, fecal microbiota transplantation (FMT) has been increasingly used as a treatment of choice for patients with ulcerative colitis (UC), but no reports exist regarding FMT via percutaneous endoscopic cecostomy (PEC). This report describes the case of a 24-year-old man with a 7-year history of recurrent, steroid-dependent UC. He received FMT via PEC once per day for 1 month in the hospital. After the remission of gastrointestinal symptoms, he was discharged from the hospital and continued FMT via PEC twice per week for 3 months at home. The frequency of stools decreased, and the characteristics of stools improved soon thereafter. Enteral nutrition was regained after 1 week, and an oral diet was begun 1 month later. Two months after the FMT end point, the patient resumed a normal diet, with formed soft stools once per day. The follow-up colonoscopy showed normal mucus membranes; then, the PEC set was removed. On the subsequent 12 months follow-up, the patient resumed orthobiosis without any gastrointestinal discomfort and returned to work. This case emphasizes that FMT via PEC can not only induce remission but also shorten the duration of hospitalization and reduce the medical costs; therefore, this approach should be considered an alternative option for patients with UC. PMID- 27282273 TI - Flexible endoscopic cricopharyngeal myotomy - The gold standard for the management of Zenker's diverticulum. AB - The prevalence of Zenker's diverticulum (ZD) is difficult to estimate. If we focus on some published data, it may be as low as 2 new cases per 100,000 inhabitants per year in the United Kingdom, which is in contrast the with feeling in some endoscopy units, that this condition's prevalence is increasing year after year. Prevalence likely remains the same as ever, but the addition of factors such as population ageing, optimal diagnostic care, availability of effective endoscopic management, increased awareness, and cumulative experience in some endoscopy teams, may well have increasingly brought this condition to our attention in our daily practice. This is reflected by an unbelievable 18 ZDs over the last 18 months, as discussed in the manuscript by Dr. de la Morena, reported in this issue of The Spanish Journal of Digestive Diseases (Revista Espanola de Enfermedades Digestivas. PMID- 27282274 TI - Rehydration methods to recover cysticercoids of the rat tapeworm Hymenolepis diminuta from dry flour beetle carcasses. AB - Terrestrial arthropods host a variety of helminth parasites, yet quantifying the intensity of infection in these hosts post-mortem is challenging because carcasses may desiccate quickly. We recovered cysticercoids of Hymenolepis diminuta from desiccated flour beetle (Tribolium confusum) carcasses by modifying a published insect rehydration procedure. Without rehydration, carcasses dissected more than 1 day post-mortem had noticeable degradation of cysticercoids. Mild rehydration (soaking in water only for 2 days, or 0.5-10% KOH for 1 h followed by 1 day in water, or 0.5% KOH for 1 day) left carcasses tough and time-consuming to dissect, but all parasites could be recovered and were similar in body size to fresh cysticercoids. Moderate rehydration (5-10% KOH for 1 day) allowed all parasites to be recovered and facilitated dissection by partially dissolving internal organs of the beetle while causing little degradation of the cysticercoids. Harsh rehydration (5-10% KOH for 1 day followed by 5 days in water) not only dissolved internal beetle tissues but also severely damaged cysticercoids, such that parasite counts were unreliable. The degree of initial carcass desiccation had little effect on results following rehydration. However, regardless of treatment used, intact cercomers were rarely retained on rehydrated cysticercoids. Rehydration was less successful on early developmental stages of the parasite, which were recovered reliably only as they neared the cysticercoid stage. This method has utility for studies of parasite-induced mortality by permitting accurate and reliable parasite counts from dead, desiccated hosts. PMID- 27282275 TI - Anodized Ti3SiC2 As an Anode Material for Li-ion Microbatteries. AB - We report on the synthesis of an anode material for Li-ion batteries by anodization of a common MAX phase, Ti3SiC2, in an aqueous electrolyte containing hydrofluoric acid (HF). The anodization led to the formation of a porous film containing anatase, a small quantity of free carbon, and silica. By varying the anodization parameters, various oxide morphologies were produced. The highest areal capacity was achieved by anodization at 60 V in an aqueous electrolyte containing 0.1 v/v HF for 3 h at room temperature. After 140 cycles performed at multiple applied current densities, an areal capacity of 380 MUAh.cm(-2) (200 MUA.cm(-2)) has been obtained, making this new material, free of additives and binders, a promising candidate as a negative electrode for Li-ion microbatteries. PMID- 27282272 TI - Differences in Clinical Manifestations according to the Positivity of Interferon gamma Assay in Patients with Intestinal Tuberculosis. AB - Intestinal tuberculosis (ITB) remains prevalent in Asia. An interferon-gamma assay (QuantiFERON-TB gold test [QFT]) is considered to be an effective supplementary tool for diagnosing ITB. We retrospectively analyzed the clinical features of ITB patients based on the initial results of QFT. A total of 109 patients with ITB were enrolled, and 82 patients (75.2%) showed positive QFT results. In the QFT-positive group, the mean age (44.1+/-12.0 years) was significantly higher than that in the QFT-negative group (37.0+/-14.8, p=0.0096). Abdominal pain (p=0.006) and diarrhea (p=0.030) were more frequent in the QFT negative group. Further, C-reactive protein (CRP) levels were significantly higher in the QFTnegative group (6.4+/-9.9 mg/dL) than in the QFT-positive group (1.3+/-2.3, p<0.001). Multivariate analysis confirmed that younger age (p=0.016), diarrhea (p=0.042), and high levels of CRP (p=0.029) were independent predictors of QFTnegative results in patients with ITB. These results suggest that prior exposure to TB, reflected by QFT positivity, may cause mild inflammation in patients with ITB. PMID- 27282276 TI - Impact of a family medicine resident wellness curriculum: a feasibility study. AB - BACKGROUND: Up to 60% of practicing physicians report symptoms of burnout, which often peak during residency. Residency is also a relevant time for habits of self care and resiliency to be emphasized. A growing literature underscores the importance of this; however, evidence about effective burnout prevention curriculum during residency remains limited. OBJECTIVES: The purpose of this project is to evaluate the impact of a new, 1-month wellness curriculum for 12 second-year family medicine residents on burnout, empathy, stress, and self compassion. METHODS: The pilot program, introduced during a new rotation emphasizing competencies around leadership, focused on teaching skills to cultivate mindfulness and self-compassion in order to enhance empathy and reduce stress. Pre-assessments and 3-month follow-up assessments on measures of burnout, empathy, self-compassion, and perceived stress were collected to evaluate the impact of the curriculum. It was hypothesized that this curriculum would enhance empathy and self-compassion as well as reduce stress and burnout among family medicine residents. RESULTS: Descriptive statistics revealed positive trends on the mean scores of all the measures, particularly the Mindfulness Scale of the Self-Compassion Inventory and the Jefferson Empathy Scale. However, the small sample size and lack of sufficient power to detect meaningful differences limited the use of inferential statistics. CONCLUSIONS: This feasibility study demonstrates how a residency wellness curriculum can be developed, implemented, and evaluated with promising results, including high participant satisfaction. PMID- 27282277 TI - Evaluating the online platform of a blended-learning pharmacist continuing education degree program. AB - BACKGROUND: Distance-based continuing education opportunities are increasingly embraced by health professionals worldwide. METHODS: To evaluate the online component of a blended-learning degree program for pharmacists, we conducted a structured self-assessment and peer review using an instrument systematically devised according to Moore's principles of transactional distance. The web-based platform for 14 courses was reviewed by both local and external faculty, followed by shared reflection of individual and aggregate results. RESULTS: Findings indicated a number of course elements for modification to enhance the structure, dialog, and autonomy of the student learning experience. CONCLUSION: Our process was an important exercise in quality assurance and is worthwhile for other health disciplines developing and delivering distance-based content to pursue. PMID- 27282278 TI - Modulation of radiation-induced oral mucositis by thalidomide : Preclinical studies. AB - PURPOSE: Oral mucositis is a common, dose-limiting early side effect of radio(chemo)therapy for head-and-neck tumors. The epithelial radiation response is accompanied by changes in the inflammatory signaling cascades mediated by the transcription factor nuclear factor-kappa B (NF-kappaB). The present study was initiated to determine the effect of the NF-kappaB inhibitor thalidomide on the clinical manifestation of oral mucositis in the established mouse tongue model. MATERIALS AND METHODS: Treatment protocols comprised single dose irradiation and daily fractionated irradiation (5 fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), alone or in combination with daily thalidomide application (100 mg/kg intraperitoneally) over varying time intervals. Fractionation protocols were terminated by graded local radiation doses (day 7/14) to generate full dose-effect curves. Tongue epithelial ulcerations, corresponding to confluent mucositis, served as the clinically relevant endpoint. RESULTS: Thalidomide application did not show a significant radioprotective potential when administered in combination with single dose irradiation. Thalidomide in combination with one week of fractionated irradiation significantly increased the isoeffective top-up doses. Similar results were observed during two weeks of fractionated irradiation in all but one experiment. CONCLUSION: Thalidomide treatment demonstrated a significant mucositis ameliorating effect during fractionated irradiation, which is likely to result from NF-kappaB inhibition. However, further mechanistic studies are required to define the underlying mechanisms of the observed mucoprotective effect. PMID- 27282280 TI - Fibrodysplasia ossificans progressiva: Case report of a Terminally-ill patient. PMID- 27282279 TI - Ablative dose proton beam therapy for stage I and recurrent non-small cell lung carcinomas : Ablative dose PBT for NSCLC. AB - PURPOSE: To evaluate the efficacy and safety of ablative dose hypofractionated proton beam therapy (PBT) for patients with stage I and recurrent non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: A total of 55 patients with stage I (n = 42) and recurrent (n = 13) NSCLC underwent hypofractionated PBT and were retrospectively reviewed. A total dose of 50-72 CGE (cobalt gray equivalent) in 5 12 fractions was delivered. RESULTS: The median follow-up duration was 29 months (range 4-95 months). There were 24 deaths (43.6%) during the follow-up period: 11 died of disease progression and 13 from other causes. Kaplan-Meier overall survival rate (OS) at 3 years was 54.9% and the median OS was 48.6 months (range 4-95 months). Local progression was observed in 7 patients and the median time to local progression was 9.3 months (range 5-14 months). Cumulative actuarial local control rate (LCR), lymph node metastasis-free survival, and distant metastasis free survival rates at 3 years were 85.4, 78.4, and 76.5%, respectively. Larger tumor diameter was significantly associated with poorer LCR (3-year: 94% for <=3 cm vs. 65% for >3 cm, p = 0.006) on univariate analysis and also an independent prognostic factor for LCR (HR 6.9, 95% CI = 1.3-37.8, p = 0.026) on multivariate analysis. No grade 3 or 4 treatment-related toxicities developed. One grade 5 treatment-related adverse event occurred in a patient with symptomatic idiopathic pulmonary fibrosis. CONCLUSIONS: Ablative dose hypofractionated PBT was safe and promising for stage I and recurrent NSCLC. PMID- 27282281 TI - miR-222 confers the resistance of breast cancer cells to Adriamycin through suppression of p27(kip1) expression. AB - Adriamycin (Adr) is a potent chemotherapeutic agent for chemotherapy of breast cancer patients. Despite impressive initial clinical responses, some developed drug resistance to Adr-based therapy and the mechanisms underlying breast cancer cells resistance to Adr are not well known. In our previous study, in vitro, we verified that miR-222 was upregulated in Adr-resistant breast cancer cells (MCF 7/Adr) compared with the sensitive parental cells (MCF-7/S). Here, miR-222 inhibitors or mimics were transfected into MCF-7 cell lines. RT-qPCR and western blot were used to detect the expression of p27(kip1). Immunofluorescence showed that miR-222 altered the subcellular location of p27(kip1) in nucleus. MTT was employed to verify the sensitivity of breast cancer cell lines to Adr. Flow cytometry showed the apoptosis and cell cycles of the cells after adding Adr. The results showed that downregulation of miR-222 in MCF-7/Adr increased sensitivity to Adr and Adr-induced apoptosis, and arrested the cells in G1 phase, accompanied by more expressions of p27(kip1), especially in nucleus. Furthermore, overexpressed miR-222 in MCF-7/S had the inverse results. Taken together, the results found that miR-222 induced Adr-resistance at least in part via suppressing p27(kip1) expression and altering its subcellular localization, and miR-222 inhibitors could reverse Adr-resistance of breast cancer cells. These results disclosed that the future holds much promise for the targeted therapeutic in the treatment of Adr-resistant breast cancer. PMID- 27282282 TI - Down-regulation of miR-133a as a poor prognosticator in non-small cell lung cancer. AB - miR-133a has been demonstrated to play an important role in tumor progression. The aim of present study was to analyze the correlation between miR-133a expression level and clinicopathologic features and its prognostic significance in non-small cell lung cancer (NSCLC). The expression of miR-133a in 104 pairs of human lung cancer tissues and adjacent normal lung tissues were analyzed by qRT PCR. Here we show that miR-133a was down-regulated in NSCLC. The levels of miR 133a were negatively correlated with the status of N classification (N0-N1 vs. N2 N3, P=0.000), clinical stage (I-II vs. III-IV, P=0.010) and MMP-14 expression (High vs. Low, P=0.012). The patients with low miR-133a expression had shorter survival time than those with high miR-133a expression. Multivariate analysis indicated that the level of miR-133a expression was an independent prognostic indicator (P=0.012) for the survival of patients with NSCLC. In conclusion, decreased expression of miR-133a might be a potential unfavorable prognostic factor for patients with NSCLC, and further studies would be needed to prove our findings. PMID- 27282283 TI - UGT2B4 previously implicated in the risk of breast cancer is associated with menarche timing in Ukrainian females. AB - Age at menarche (AAM) is a multifactorial trait that is regulated by dozens environmental and genetic factors. Recent meta-analysis of GWAS showed significant association of 106 loci with AAM. These polymorphisms need replicating in different ethnic populations in order to confirm their association with menarche timing. This study was aimed to replicate 53 polymorphisms that were previously associated with AAM. DNA samples were collected from 416 Ukrainian young females for further genotyping. After data quality control 47 polymorphisms remained for the association analysis using the linear regression model. SNP rs13111134 located in UGT2B4 showed the most significant association with AAM (0.431years per allele A, padj=0.044 after the Bonferroni correction). Polymorphisms rs7589318 in POMC, rs11724758 in FABP2, rs7753051 in IGF2R, rs2288696 in FGFR1 and rs12444979 in GPRC5B may also contribute to menarche timing. However, none of these associations remained significant after the Bonferroni correction for multiple testing. The obtained results provide evidence that UGT2B4, which was previously associated with predisposition to breast cancer, may play a role in the onset of menarche. PMID- 27282284 TI - Enantioselective synthesis of cyanohydrins catalysed by hydroxynitrile lyases - a review. AB - The first enantioselective synthesis was the selective addition of cyanide to benzaldehyde catalysed by a hydroxynitrile lyase (HNL). Since then these enzymes have been developed into a reliable tool in organic synthesis. HNLs to prepare either the (R)- or the (S)-enantiomer of the desired cyanohydrin are available and a wide variety of reaction conditions can be applied. As a result of this, numerous applications of these enzymes in organic synthesis have been described. Here the examples of the last decade are summarised, the enzyme catalysed step is discussed and the follow-up chemistry is shown. This proves HNLs to be part of main stream organic synthesis. Additionally the newest approaches via immobilisation and reaction engineering are introduced. PMID- 27282286 TI - Systems biology of viral infection. PMID- 27282285 TI - Risk Factors for Cataracts Treated Surgically in Postmenopausal Women. AB - PURPOSE: To identify risk factors for cataracts treated surgically in postmenopausal women. DESIGN: Population-based, prospective cohort study. PARTICIPANTS: A total of 1 312 051 postmenopausal women in the UK Million Women Study, aged 56 years on average (standard deviation [SD], 4.8), without previous cataract surgery, hospital admission with cataracts, or cancer at baseline, were followed for cataracts treated surgically. METHODS: Cox regression was used to calculate adjusted relative risks (RRs) for cataract surgery by lifestyle factors, treatment for diabetes, reproductive history, and use of hormonal therapies. MAIN OUTCOME MEASURES: Cataract surgery identified by linkage to central National Health Service (NHS) records for inpatient and day-patient admissions (Hospital Episode Statistics for England and Scottish Morbidity Records in Scotland). RESULTS: Overall, 89 343 women underwent cataract surgery during an average of 11 (SD, 3) years of follow-up. Women with diabetes were at greatest risk (diabetes vs. no diabetes RR, 2.90; 95% confidence interval [CI], 2.82-2.97). Other factors associated with an increased risk of cataract surgery were current smoking (current smokers of >=15 cigarettes/day vs. never smokers RR, 1.26; 95% CI, 1.23-1.30) and obesity (body mass index [BMI] >=30 vs. <25 kg/m(2); RR, 1.12; 95% CI, 1.10-1.14). CONCLUSIONS: Diabetes, smoking, and obesity were risk factors for cataract surgery. Alcohol use, physical activity, reproductive history, and use of hormonal therapies had little, if any, association with cataract surgery risk. PMID- 27282287 TI - Atomic scale mobility of the volatile fission products Xe, Kr and I in cubic SiC. AB - The migration barriers for the vacancy-assisted migration of fission products in 3C-SiC are reported and analysed in the context of the five frequency model, which enables one to calculate an effective diffusion coefficient from elementary mechanisms. Calculations were carried out using the nudged elastic band method (NEB) with interatomic forces determined from density functional theory (DFT). Justification for treating vacancy-assisted fission product migration as limited to the FCC carbon sublattice is based on the stability of carbon vacancies, unfavourable silicon vacancy formation and the accommodation of fission products on the carbon sublattice. Results show that for most Fermi levels within the band gap the activation energy for I exceeds that of Xe which exceeds that of Kr. Results also indicate that activation energies are higher near the conduction edge, thus, implying that enhanced fission product retention can be achieved through n-type doping of 3C-SiC, which limits the availability of the migration mediating carbon vacancies. PMID- 27282288 TI - Spectral Pathology: general discussion. PMID- 27282289 TI - Safety and feasibility of fasting in combination with platinum-based chemotherapy. AB - BACKGROUND: Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum based chemotherapy to determine safety and feasibility in cancer patients. METHODS: 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as >= 3/6 subjects in each cohort consuming <= 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state. RESULTS: The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to <= grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for >=48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period. CONCLUSION: Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An onging randomized trial is studying the effect of 72 h of fasting. TRIAL REGISTRATION: NCT00936364 , registered propectively on July 9, 2009. PMID- 27282290 TI - Rare disease landscape in Brazil: report of a successful experience in inborn errors of metabolism. AB - Brazil is a country of continental dimensions, with many social inequalities. The latter are reflected on its health system, which comprises a large public component called SUS, a small paid health insurance component and a third very small private component, in which patients pay personally for medical services. Seventy five percent of the population depends on SUS, which thus far does not provide adequate coverage for genetic medical procedures. In 2014, SUS introduced the "Policy for the Integral Attention to Subjects with Rare Diseases", establishing guidelines for offering diagnosis and treatment. The policy defines the two main axes, genetic and non-genetic rare diseases. In this fashion, public genetic services in SUS will be installed and funded not by themselves, but as part of the more general policy of rare diseases. Unfortunately, up to now this policy is still depending on financial allowances to be effectively launched. In this article, our intention was to describe activities developed in the area of inborn errors of metabolism by a Brazilian reference center. In spite of the lack of support of SUS, thousands of Brazilian families affected by rare genetic metabolic disorders, and many health professionals from all regions of Brazil, already have benefited from the services, training programs and research projects provided by this comprehensive center. PMID- 27282292 TI - Farewell and thanks to Dave Sackett, Cochrane's first pilot. PMID- 27282294 TI - Corrigendum to "Blood collection, components preparation and distribution in Iran, 2008-2012" [Transfus Apher Sci 54 (2016) 117-121]. PMID- 27282293 TI - Paradoxical reaction to antituberculosis therapy after 6 months of treatment for pulmonary tuberculosis: A case report. AB - Paradoxical reactions (PRs) to antituberculosis (anti-TB) drugs during treatment are well known phenomena, but a PR presenting as a new pulmonary lesion after completion of treatment is extremely rare, and little is known about the management of such cases. A 44-year-old man was diagnosed with pulmonary TB. His sputum cultures became negative 45 days after the initiation of standard anti-TB treatment. Upon the patient's completion of 6 months of anti-TB therapy, computed tomography revealed a new irregularly shaped mass in the lower left pulmonary lobe. A transbronchial lung biopsy (TBLB) revealed caseous necrosis and granulomatosis surrounded by epithelioid and multinucleated giant cells. Cultures of both the TBLB specimen and bronchoalveolar lavage fluid remained negative for TB. The CT shadow disappeared 6 months later without further administration of anti-TB drugs. Careful observation without therapy may be sufficient for a patient treated for TB who develops a PR upon completion of treatment, if the patient has achieved a bacteriological remission. PMID- 27282291 TI - Influence of PapMV nanoparticles on the kinetics of the antibody response to flu vaccine. AB - BACKGROUND: The addition of an adjuvant to a vaccine is a promising approach to increasing strength and immunogenicity towards antigens. Despite the fact that adjuvants have been used in vaccines for decades, their mechanisms of action and their influence on the kinetics of the immune response are still not very well understood. The use of papaya mosaic virus (PapMV) nanoparticles-a novel TLR7 agonist-was recently shown to improve and broaden the immune response directed to trivalent inactivated flu vaccine (TIV) in mice and ferrets. RESULTS: We investigated the capacity of PapMV nanoparticles to increase the speed of the immune response toward TIV. PapMV nanoparticles induced a faster and stronger humoral response to TIV that was measured as early as 5 days post-immunization. The addition of PapMV nanoparticles was shown to speed up the differentiation of B-cells into early plasma cells, and increased the growth of germinal centers in a CD4+ dependent manner. TIV vaccination with PapMV nanoparticles as an adjuvant protected mice against a lethal infection as early as 10 days post-immunization. CONCLUSION: In conclusion, PapMV nanoparticles are able to accelerate a broad humoral response to TIV. This property is of the utmost importance in the field of vaccination, especially in the case of pandemics, where populations need to be protected as soon as possible after vaccination. PMID- 27282295 TI - Functional dyspepsia and dyspepsia associated with Helicobacter pylori infection: Do they have different clinical characteristics? AB - BACKGROUND: Helicobacter pylori causes motor, secretory, and inflammatory gastrointestinal disorders and therefore the term "functional" has been questioned when referring to dyspepsia associated with this bacterium. Patients with dyspepsia and Helicobacter pylori infection could have clinical characteristics that differentiate them a priori from those with true functional dyspepsia. AIMS: To determine whether there are clinical differences between patients with functional dyspepsia and Helicobacter pylori-associated dyspepsia that enable their a priori identification and to know the prevalence of Helicobacter pylori infection in patients with functional dyspepsia. PATIENTS AND METHODS: A total of 578 patients with dyspepsia with no significant lesions detectable through endoscopy were divided into 2 groups according to the presence of Helicobacter pylori. The clinical characteristics, medical history, comorbidities, and use of health resources were compared between the two groups. A sub-analysis pairing the groups by age and sex in a 1:1 ratio was carried out to reduce bias. RESULTS: A total of 336 patients infected with Helicobacter pylori were compared with 242 non-infected patients. The prevalence of infection in the patients with dyspeptic symptoms and no endoscopically detectable lesions was 58%. The initial analysis showed that the cases with dyspepsia and Helicobacter pylori infection were more frequently associated with overweight, obesity, high blood pressure, diabetes mellitus, and metabolic syndrome, but the paired analysis nullified all these differences. CONCLUSIONS: The patients with dyspepsia infected with Helicobacter pylori had similar clinical characteristics to the non-infected patients and could not be differentiated a priori. The prevalence of Helicobacter pylori infection in patients with functional dyspepsia was 58% and increased with age. PMID- 27282297 TI - Mobilization and removing of cadmium from kidney by GMDTC utilizing renal glucose reabsorption pathway. AB - Chronic exposure to cadmium compounds (Cd(2+)) is one of the major public health problems facing humans in the 21st century. Cd(2+) in the human body accumulates primarily in the kidneys which leads to renal dysfunction and other adverse health effects. Efforts to find a safe and effective drug for removing Cd(2+) from the kidneys have largely failed. We developed and synthesized a new chemical, sodium (S)-2-(dithiocarboxylato((2S,3R,4R,5R)-2,3,4,5,6 pentahydroxyhexyl)amino)-4-(methylthio) butanoate (GMDTC). Here we report that GMDTC has a very low toxicity with an acute lethal dose (LD50) of more than 10,000mg/kg or 5000mg/kg body weight, respectively, via oral or intraperitoneal injection in mice and rats. In in vivo settings, up to 94% of Cd(2+) deposited in the kidneys of Cd(2+)-laden rabbits was removed and excreted via urine following a safe dose of GMDTC treatment for four weeks, and renal Cd(2+) level was reduced from 12.9MUg/g to 1.3MUg/g kidney weight. We observed similar results in the mouse and rat studies. Further, we demonstrated both in in vitro and in animal studies that the mechanism of transporting GMDTC and GMDTC-Cd complex into and out of renal tubular cells is likely assisted by two glucose transporters, sodium glucose cotransporter 2 (SGLT2) and glucose transporter 2 (GLUT2). Collectively, our study reports that GMDTC is safe and highly efficient in removing deposited Cd(2+) from kidneys assisted by renal glucose reabsorption system, suggesting that GMDTC may be the long-pursued agent used for preventive and therapeutic purposes for both acute and chronic Cd(2+) exposure. PMID- 27282296 TI - Understanding cognition in older patients with cancer. AB - Cancer and neurocognitive disorders, such as dementia and delirium, are common and serious diseases in the elderly that are accompanied by high degree of morbidity and mortality. Furthermore, evidence supports the under-diagnosis of both dementia and delirium in older adults. Complex questions exist regarding the interaction of dementia and delirium with cancer, beginning with guidelines on how best measure disease severity, the optimal screening test for either disorder, the appropriate level of intervention in the setting of abnormal findings, and strategies aimed at preventing the development or progression of either process. Ethical concerns emerge in the research setting, pertaining to the detection of cognitive dysfunction in participants, validity of consent, disclosure of abnormal results if screening is pursued, and recommended level of intervention by investigators. Furthermore, understanding the ways in which comorbid cognitive dysfunction and cancer impact both cancer and non-cancer related outcomes is essential in guiding treatment decisions. In the following article, we will discuss what is presently known of the interactions of pre existing cognitive impairment and delirium with cancer. We will also discuss identified deficits in our knowledge base, and propose ways in which innovative research may address these gaps. PMID- 27282298 TI - Regulation of rat plasma and cerebral cortex oxylipin concentrations with increasing levels of dietary linoleic acid. AB - Linoleic acid (LA, 18:2n-6) is the most abundant polyunsaturated fatty acid in the North American diet and is a precursor to circulating bioactive fatty acid metabolites implicated in brain disorders. This exploratory study tested the effects of increasing dietary LA on plasma and cerebral cortex metabolites derived from LA, its elongation-desaturation products dihomo-gamma linolenic (DGLA, 20:3n-6) acid and arachidonic acid (AA, 20:4n-6), as well as omega-3 alpha linolenic (alpha-LNA, 18:3n-3), eicosapentaenoic (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Plasma and cortex were obtained from rats fed a 0.4%, 5.2% or 10.5% energy LA diet for 15 weeks and subjected to liquid chromatography tandem mass spectrometry analysis. Total oxylipin concentrations, representing the esterified and unesterified pool, and unesterified oxylipins derived from LA and AA were significantly increased and EPA metabolites decreased in plasma at 5.2% or 10.5% energy LA compared to 0.4% energy LA. Unesterified plasma DHA metabolites also decreased at 10.5% energy LA. In cortex, total and unesterified LA and AA metabolites increased and unesterified EPA metabolites decreased at 5.2% or 10.5% LA. DGLA and alpha-LNA metabolites did not significantly change in plasma or cortex. Dietary LA lowering represents a feasible approach for targeting plasma and brain LA, AA, EPA or DHA-derived metabolite concentrations. PMID- 27282299 TI - Identification of Covert Atrial Fibrillation in Cryptogenic Ischemic Stroke: Current Clinical Practice in Japan. AB - BACKGROUND AND AIM: A new insertable cardiac monitor, Reveal LINQ (Medtronic, Dublin, Ireland), was approved for clinical use in Japan in March 2016 for detecting atrial fibrillation in patients who develop ischemic stroke with no clearly definable etiology even after extensive workup, so-called cryptogenic ischemic stroke. Cooperation between a specialist of the Japan Stroke Society and a trained cardiologist or cardiac surgeon is needed both for appropriate patient selection and appropriate management of the device. In this paper, the clinical significance of and diagnostic methods for cryptogenic stroke and covert atrial fibrillation are explained, along with our proposal for the clinical indications for this new device. METHODS, RESULTS, AND CONCLUSION: The majority of cryptogenic ischemic strokes are considered to be embolic. In particular, covert atrial fibrillation is drawing attention as the causal emboligenic disease, and it was identified in 30% of patients with long-term observation using an insertable cardiac monitor. Should atrial fibrillation be present, there is a high risk of recurrent stroke, and the cardioembolic stroke that appears is generally severe. The ability to identify atrial fibrillation would be beneficial for preventing stroke recurrence, as anticoagulants can then be used as an established method of secondary prevention. Because the use of insertable cardiac monitors is somewhat invasive, and long-term care systems are also needed, patients suitable for examination using the new device would need to be identified on the basis of detailed diagnostics in accordance withcurrent medical practice in Japan. PMID- 27282300 TI - Faciolingual Hemiparesis with Mild Limb Weakness of Cortical Origin. AB - The clinical combination of unilateral facial and hypoglossal palsy with upper limb weakness is known as the capsular genu syndrome and responds most often to an ischemic infarct in the internal capsule. We here describe a patient with this peculiar combination, in whom the responsible lesion was located in the contralateral prefrontal cortex, involving the corresponding areas of the Penfield's homunculus. Contralateral cortical frontal lesions should be considered in patients with facial and hypoglossal palsy with upper limb weakness. PMID- 27282301 TI - Mechanical Thrombectomy in Acute Ischemic Stroke-Patients with Wake-Up Stroke and the Elderly May Benefit as Well. AB - BACKGROUND: We have assessed to what extent age, sex, preintervention infarct size, time to groin puncture, and stroke severity are associated with outcome of mechanical thrombectomy in patients treated for acute ischemic stroke. METHODS: All 192 patients treated with mechanical thrombectomy for acute ischemic stroke from September 2005 to December 2011 were included in this observational study. Main outcomes were independence, defined as a modified Rankin Scale score of 0-2, an improvement in stroke severity score post-thrombectomy, and the occurrence of symptomatic hemorrhage. Exposure variables were sex, age, intravenous thrombolysis, prethrombectomy stroke severity grading, pretreatment infarct size, time from onset of symptoms to groin puncture, thrombectomy device used, and the angiographic result from the thrombectomy. RESULTS: For patients above 50 years with no neurological symptoms before stroke onset, the proportion gaining independence was unrelated to age group, ranging from 49% to 54%. For patients younger than 50 years of age, the proportion was significantly higher (81%). Patients with wake-up stroke did not differ from other patients with regard to outcome. CONCLUSIONS: Our results emphasize that when patients are selected on the basis of angiographic and perfusion imaging, both older patients and patients with wake-up stroke may experience a favorable outcome after mechanical thrombectomy. PMID- 27282302 TI - Giant Posterior Communicating Artery Aneurysm Presenting as Trigeminal Neuralgia. AB - BACKGROUND: We report an extremely rare case of trigeminal neuralgia (TN) caused by a giant posterior communicating artery aneurysm. METHODS: We describe the case of a 73-year-old man who suffered disabling TN, which was deeply exacerbated when he laid down. Computed tomography angiography and digital angiography revealed an unruptured giant posterior left communicating artery aneurysm projecting to the posterior fossa and contacting the trigeminal root. RESULTS: The size and projection of the aneurysm seemed responsible for both the neuralgia itself and its peculiar clinical characteristic of exacerbation when the patient laid down. The aneurysm was surgically clipped, then opened and emptied to decompress the trigeminal root. The patient reported an immediate complete remission of the neuralgia. CONCLUSION: The finding of TN secondary to aneurysms is rare but even more in the case of a posterior communicating aneurysm. The clinical clue that should alert physicians about the presence of an aneurysm as the cause of TN is exacerbation of pain by adopting a supine position. Due to the high risk of rupture associated with giant and symptomatic aneurysms, we believe that treatment should be aggressive in this case, not only to solve the symptomatic TN but also to avoid the risk of aneurysm rupture in the future. The treatment selection between surgical clipping or endovascular coiling with or without stenting, depends on patient's clinical condition and the size and shape of the aneurysm. PMID- 27282303 TI - Neurological Involvement in the Course of Scleromyxedema: A Case Report. AB - Scleromyxedema is a rare disease of unknown etiology primarily affecting the skin, characterized by generalized papular eruption, dermal fibroblast proliferation with mucin deposition, and a monoclonal gammopathy. Neurological impairment is a rare but sometimes fatal complication of scleromyxedema that should be rapidly identified to prevent significant morbidity and mortality. A 63 year-old Caucasian man had a 2-year history of scleromyxedema, and was under immunosuppressive treatment with ciclosporine and methotrexate. The patient came to our attention because of sudden neurological dysfunction with altered sensorium, confusion, and dysarthria. After a few hours since admission, the patient developed left hemiparesis, followed after 2 days by right hemiparesis. The brain computed tomography and cerebrospinal fluid examination results were normal. Brain magnetic resonance imaging (MRI) showed a bilateral cortical hyperintense signal on T2 sequences with leptomeningeal enhancement. Extensive serological and liquoral evaluations were performed without significant findings. After steroid initiation, a remarkable neurological improvement was noticed. The dramatic and immediate response of the patient's to steroid and MRI data strongly suggested a dysimmune etiology. Over the ensuing week, the patient's language, motor, and sensory functions continued to improve. Two weeks after admission, the patient was discharged to home without significant neurological sequelae. PMID- 27282305 TI - Auditory hallucinations in the population: what do they mean and what should we do about them? PMID- 27282304 TI - Prevalence and Prognostic Significance of Runs of Premature Atrial Complexes in Ischemic Stroke Patients. AB - BACKGROUND AND PURPOSE: Runs of premature atrial complexes (PACs) are common in stroke patients and perceived to be clinically insignificant, but their prognostic significance is unclear. This study investigated the association between runs of PACs in ischemic stroke patients and the risk of recurrent ischemic strokes/transient ischemic attacks (TIAs) or death. METHODS: The study included consecutive patients admitted with an ischemic stroke from August 2008 to April 2011. Patients with known and newly detected atrial fibrillation were excluded. Runs of PACs were defined as 3 or more PACs lasting less than 30 seconds during 48 hours of continuous inpatient cardiac telemetry. The patients were followed for 4 years or until death, whichever came first. They were stratified according to stroke severity. The combined primary endpoint was a recurrent ischemic stroke/TIA or death. RESULTS: Of the 565 patients included in the study, 28% had runs of PACs. Patients with runs of PACs were likely to be older, female, and to have experienced more severe strokes. During the follow-up, 210 (37%) patients had a recurrent ischemic stroke/TIA (n = 73) or died (n = 137) respectively. Among the 489 patients who had mild-to-moderate strokes, runs of PACs were associated with recurrent ischemic strokes/TIAs or death (hazard ratio = 1.47; 95% CI 1.06-2.04; P = .023). CONCLUSION: Runs of PACs were frequent in patients with acute ischemic strokes and sinus rhythm, and they were independently associated with an increased risk of recurrent ischemic strokes/TIAs or death in patients with mild-to-moderate strokes. PMID- 27282306 TI - Brimonidine Toxicity Secondary to Topical Use for an Ulcerated Hemangioma. AB - Combigan (Allergan, Irvine, CA) is an ophthalmic solution that combines 0.2% brimonidine, a selective alpha-2 adrenergic agonist, with 0.5% timolol, a nonselective beta-adrenergic antagonist. It is approved for the reduction of intraocular pressure in patients with glaucoma or ocular hypertension. There have been recent reports of successful treatment of superficial infantile hemangiomas (IHs) using Combigan topically. We report the case of a 2-month-old girl who developed life-threatening brimonidine toxicity requiring intubation and mechanical ventilation secondary to central nervous system depression and apnea after topical application to an ulcerated IH. PMID- 27282308 TI - Does a Multimodal No-Compression Suture Technique of the Intercostal Space Reduce Chronic Postthoracotomy Pain? A Prospective Randomized Study. AB - INTRODUCTION: Chronic postthoracotomy pain is a significant adverse outcome of thoracic surgery. We evaluated with a prospective randomized trial the effect of a multimodal no-compression suture technique of the intercostal space on postoperative pain occurrence in patients undergoing minithoracotomy. METHODS: Patients undergoing a muscle-sparing lateral minithoracotomy for different thoracic diseases were randomly divided into two groups: 146 patients received intercostal muscle flap harvesting and pericostal no-compression "edge" suture (the IMF group), and 151 patients received a standard suture technique associated with an intrapleural intercostal nerve block (the IINB group). Pain scores and interference of pain with daily activities were assessed by using the Italian version of the Brief Pain Inventory on day 1, and at 1 to 6 months postoperatively. The results of pulmonary function tests (spirometry and the 6 minute walking test ) were evaluated preoperatively and at 1 and 6 months postoperatively. RESULTS: Postthoracotomy pain scores throughout the first postoperative day were significantly lower in the IMF group. After 1 and 6 months, patients in the IMF group had a significantly lower average pain score (p = 0.001). There were no significant differences in pain interference scores at each evaluation time point in either group. However, differences were shown in lung function test results at 1 and 6 months postoperatively (the forced expiratory volume in 1 second in the IINB group averaged 68.8 +/- 17.4% of predicted value and 72.8 +/- 10.5%, respectively, and in the IMF group it averaged 83.1 +/- 7.4% and 86.4 +/- 12.8%, respectively [p = 0.023 and 0.013, respectively]; the 6-minute walking test results in the IINB group averaged 311.1 +/- 51.0 and 329.9 +/- 54.8 m, respectively, and those in the IMF group averaged 371.2 +/- 54.8 and 395.7 +/- 56.4 m, respectively [p = 0.0001]). CONCLUSIONS: The multimodal no-compression suture technique is a rapid and feasible procedure that reduces the intensity of early and chronic postthoracotomy pain. PMID- 27282307 TI - In vitro microbicidal, anti-biofilm and cytotoxic effects of different commercial antiseptics. AB - Topical antiseptics are widely used for wound treatment, with the goal of disrupting biofilm capacity. We analysed the effectiveness of a variety of antiseptics to inhibit various stages of biofilm formation and to remove biofilms in vitro as well as the agents' cytotoxic effects on fibroblasts. We found that the chlorine-releasing agents exhibited immediate anti-biofilm effects in the short term, with lesser cytotoxicity than agents prepared from more stable compounds, such as biguanide or modified diallyl disulfide-oxide, which, conversely, have better long-term effectiveness. Among the examined organisms, Gram-positive bacteria and Candida albicans were the most sensitive to the antiseptics, whereas Pseudomonas aeruginosa and Acinetobacter baumannii were relatively resistant to them. Formulations whose mechanisms of action involve the release of chemically active chlorine were more effective when administered in solution than the gel form, likely because of the stability of the active ingredients during or after preparation of the formula. Interestingly, hypochlorous acid and some superoxidation solutions were effective in preventing biofilm formation within a short time period and showed virtually no toxicity. Our study indicates that most antiseptics remain effective long enough to prevent biofilm formation; thus, even brief application of an antiseptic agent during initial wound treatment can lead to better wound management outcomes. PMID- 27282309 TI - The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing. AB - Malignant pleural mesothelioma (MPM) is a rare yet aggressive tumor that is causally associated with-mostly professional-asbestos exposure. Given the long latency between exposure and disease, and because asbestos is still being used, MPM will remain a global health issue for decades to come. Notwithstanding the increasing incidence of MPM and the fact that patients with MPM face a poor prognosis, currently available treatment options are limited. To enable the development of novel targeted therapies, identification of the genetic alterations underlying MPM will be crucial. The first studies reporting on the genomic background of MPM identified recurrent somatic mutations in a number of tumor suppressor genes (i.e., cyclin-dependent kinase inhibitor 2A gene [CDKN2A], neurofibromin 2 (merlin) gene [NF2], and BRCA1 associated protein 1 gene [BAP1]). More recently, massively parallel sequencing strategies have been used and have provided a more genome-wide view on the genetic landscape of MPM. This review summarizes their results, describing alterations that cluster mainly in four pathways: the tumor protein p53/DNA repair, cell cycle, mitogen-activated protein kinase, and phosphoinisitide 3-kinase (PI3K)/AKT pathways. As these pathways are important during tumor development, they provide interesting candidates for targeting with novel drugs. PMID- 27282310 TI - Factor XII: form determines function. AB - Factor XII is a mysterious plasma protein without a clear physiologic function. It was identified as a clotting factor, but has no clear role in hemostasis. However, FXII also contributes to the production of bradykinin, a short-lived inflammatory peptide. A growing body of mechanistic research from animal models indicates that FXII contributes to thrombotic disease by triggering excessive coagulation. FXII is evolutionarily conserved, suggesting that this molecule does have a physiologic function. This leads to intriguing questions: What does FXII really do? Is it even a real clotting factor at all? Before the groundbreaking discovery of a role for FXII in thrombotic disease, many studies investigated the biochemical properties of FXII and its activators. In this review, we highlight several biochemical studies that reveal much about the natural behavior of FXII. On the basis of these findings, it is possible to draft a conceptual model to explain how FXII reacts to surface materials. We then discuss how this model applies to the activities of FXII in its natural environment. There are two tentative physiologic functions of FXII that can operate exclusively: (i) maintenance of thrombus stability; (ii) local regulation of vascular permeability. Either, or both, of these natural functions may explain the evolutionary development and maintenance of FXII. PMID- 27282311 TI - A Cost-Benefit Analysis of a Family Systems Intervention for Managing Pediatric Chronic Illness. AB - Despite recent increases of psychosocial programs for pediatric chronic illness, few studies have explored their economic benefits. This study investigated the costs-benefits of a family systems-based, psychosocial intervention for pediatric chronic illness (MEND: Mastering Each New Direction). A quasi-prospective study compared the 12-month pre-post direct and indirect costs of 20 families. The total cost for program was estimated to $5,320. Families incurred $15,249 less in direct and $15,627 less in indirect costs after MEND. On average, medical expenses reduced by 86% in direct and indirect costs, for a cost-benefit ratio of 0.17. Therefore, for every dollar spent on the program, families and their third payers saved approximately $5.74. Implications for healthcare policy and reimbursements are discussed. PMID- 27282312 TI - Ecology Letters, and Transparency and Openness Promotion (TOP) guidelines. PMID- 27282313 TI - Promoting transparency in evolutionary biology and ecology. PMID- 27282314 TI - N-dimensional hypervolumes to study stability of complex ecosystems. AB - Although our knowledge on the stabilising role of biodiversity and on how it is affected by perturbations has greatly improved, we still lack a comprehensive view on ecosystem stability that is transversal to different habitats and perturbations. Hence, we propose a framework that takes advantage of the multiplicity of components of an ecosystem and their contribution to stability. Ecosystem components can range from species or functional groups, to different functional traits, or even the cover of different habitats in a landscape mosaic. We make use of n-dimensional hypervolumes to define ecosystem states and assess how much they shift after environmental changes have occurred. We demonstrate the value of this framework with a study case on the effects of environmental change on Alpine ecosystems. Our results highlight the importance of a multidimensional approach when studying ecosystem stability and show that our framework is flexible enough to be applied to different types of ecosystem components, which can have important implications for the study of ecosystem stability and transient dynamics. PMID- 27282315 TI - Defensive insect symbiont leads to cascading extinctions and community collapse. AB - Animals often engage in mutualistic associations with microorganisms that protect them from predation, parasitism or pathogen infection. Studies of these interactions in insects have mostly focussed on the direct effects of symbiont infection on natural enemies without studying community-wide effects. Here, we explore the effect of a defensive symbiont on population dynamics and species extinctions in an experimental community composed of three aphid species and their associated specialist parasitoids. We found that introducing a bacterial symbiont with a protective (but not a non-protective) phenotype into one aphid species led to it being able to escape from its natural enemy and increase in density. This changed the relative density of the three aphid species which resulted in the extinction of the two other parasitoid species. Our results show that defensive symbionts can cause extinction cascades in experimental communities and so may play a significant role in the stability of consumer herbivore communities in the field. PMID- 27282317 TI - Invasion fitness, inclusive fitness, and reproductive numbers in heterogeneous populations. AB - How should fitness be measured to determine which phenotype or "strategy" is uninvadable when evolution occurs in a group-structured population subject to local demographic and environmental heterogeneity? Several fitness measures, such as basic reproductive number, lifetime dispersal success of a local lineage, or inclusive fitness have been proposed to address this question, but the relationships between them and their generality remains unclear. Here, we ascertain uninvadability (all mutant strategies always go extinct) in terms of the asymptotic per capita number of mutant copies produced by a mutant lineage arising as a single copy in a resident population ("invasion fitness"). We show that from invasion fitness uninvadability is equivalently characterized by at least three conceptually distinct fitness measures: (i) lineage fitness, giving the average individual fitness of a randomly sampled mutant lineage member; (ii) inclusive fitness, giving a reproductive value weighted average of the direct fitness costs and relatedness weighted indirect fitness benefits accruing to a randomly sampled mutant lineage member; and (iii) basic reproductive number (and variations thereof) giving lifetime success of a lineage in a single group, and which is an invasion fitness proxy. Our analysis connects approaches that have been deemed different, generalizes the exact version of inclusive fitness to class-structured populations, and provides a biological interpretation of natural selection on a mutant allele under arbitrary strength of selection. PMID- 27282316 TI - How mutualisms arise in phytoplankton communities: building eco-evolutionary principles for aquatic microbes. AB - Extensive sampling and metagenomics analyses of plankton communities across all aquatic environments are beginning to provide insights into the ecology of microbial communities. In particular, the importance of metabolic exchanges that provide a foundation for ecological interactions between microorganisms has emerged as a key factor in forging such communities. Here we show how both studies of environmental samples and physiological experimentation in the laboratory with defined microbial co-cultures are being used to decipher the metabolic and molecular underpinnings of such exchanges. In addition, we explain how metabolic modelling may be used to conduct investigations in reverse, deducing novel molecular exchanges from analysis of large-scale data sets, which can identify persistently co-occurring species. Finally, we consider how knowledge of microbial community ecology can be built into evolutionary theories tailored to these species' unique lifestyles. We propose a novel model for the evolution of metabolic auxotrophy in microorganisms that arises as a result of symbiosis, termed the Foraging-to-Farming hypothesis. The model has testable predictions, fits several known examples of mutualism in the aquatic world, and sheds light on how interactions, which cement dependencies within communities of microorganisms, might be initiated. PMID- 27282318 TI - A Visible-Light-Active Heterojunction with Enhanced Photocatalytic Hydrogen Generation. AB - A visible-light-active carbon nitride (CN)/strontium pyroniobate (SNO) heterojunction photocatalyst was fabricated by deposition of CN over hydrothermally synthesized SNO nanoplates by a simple thermal decomposition process. The microscopic study revealed that nanosheets of CN were anchored to the surface of SNO resulting in an intimate contact between the two semiconductors. Diffuse reflectance UV/Vis spectra show that the resulting CN/SNO heterojunction possesses intense absorption in the visible region. The structural and spectral properties endowed the CN/SNO heterojunction with remarkably enhanced photocatalytic activity. Specifically, the photocatalytic hydrogen evolution rate per mole of CN was found to be 11 times higher for the CN/SNO composite compared to pristine CN. The results clearly show that the composite photocatalyst not only extends the light absorption range of SNO but also restricts photogenerated charge-carrier recombination, resulting in significant enhancement in photocatalytic activity compared to pristine CN. The relative band positions of the composite allow the photogenerated electrons in the conduction band of CN to migrate to that of SNO. This kind of charge migration and separation leads to the reduction in the overall recombination rate of photogenerated charge carriers, which is regarded as one of the key factors for the enhanced activity. A plausible mechanism for the enhanced photocatalytic activity of the heterostructured composite is proposed based on observed activity, photoluminescence, time-resolved fluorescence emission decay, electrochemical impedance spectroscopy, and band position calculations. PMID- 27282319 TI - The Chemical Shift Baseline for High-Pressure NMR Spectra of Proteins. AB - High-pressure (HP) NMR spectroscopy is an important method for detecting rare functional states of proteins by analyzing the pressure response of chemical shifts. However, for the analysis of the shifts it is mandatory to understand the origin of the observed pressure dependence. Here we present experimental HP NMR data on the (15) N-enriched peptide bond model, N-methylacetamide (NMA), in water, combined with quantum-chemical computations of the magnetic parameters using a pressure-sensitive solvation model. Theoretical analysis of NMA and the experimentally used internal reference standard 4,4-dimethyl-4-silapentane-1 sulfonic (DSS) reveal that a substantial part of observed shifts can be attributed to purely solvent-induced electronic polarization of the backbone. DSS is only marginally responsive to pressure changes and is therefore a reliable sensor for variations in the local magnetic field caused by pressure-induced changes of the magnetic susceptibility of the solvent. PMID- 27282320 TI - Comprehensive Electrocardiographic Analysis of Lead Exposed Workers: An Arrhythmic Risk Assessment Study. AB - BACKGROUND: To evaluate electrocardiographic parameters which are related with atrial and ventricular arrhythmias measured from 12-lead surface electrocardiogram (ECG) in workers occupationally exposed to lead. METHODS: Sixty lead-exposed workers and 60 healthy controls were enrolled. Twelve-lead surface ECG was recorded and measurements of P wave durations (Pmax, Pmin) and P wave dispersion (PWD), QT durations and dispersion (QTd), corrected QT (QTc), Tp-e interval, and Tp-e/QT ratio were analyzed. RESULTS: The lead-exposed and control groups were similar with respect to baseline demographic, laboratory, and transthoracic echocardiographic indices. PWD (26.3 +/- 9.7 vs 22.0 +/- 9.0 ms, P = 0.014), Pmin (89.9 +/- 13.8 vs 79.2 +/- 10.1 ms, P < 0.001), and Pmax (116.2 +/ 15.0 vs 101.2 +/- 14.2 ms, P < 0.001), QT maximum (377.0 +/- 27.6 vs 364.9 +/- 28.5 ms, P = 0.02), QTd (38.4 +/- 16.5 vs 30.5 +/- 12.4 ms, P = 0.004), Tp-e interval (78.9 +/- 16.5 vs 70.3 +/- 14.5 ms, P = 0.003), and Tp-e/QT ratio (0.22 +/- 0.04 vs 0.20 +/- 0.04, P = 0.013) were significantly higher in lead-exposed workers. QT minimum and QTc values did not differ significantly. QT maximum, QTd, and Tp-e/QT ratio were correlated with urine lead level and Tp-e interval was correlated with both blood and urine lead levels. CONCLUSIONS: Lead-exposed workers have a higher risk for atrial and ventricular arrhythmias even without overt cardiac diseases compared with healthy subjects. These workers should be followed closely for adverse cardiovascular outcomes especially arrhythmias. PMID- 27282321 TI - Forest drought as an emerging research priority. PMID- 27282322 TI - Do trace metals select for darker birds in urban areas? An experimental exposure to lead and zinc. AB - Trace metals from anthropogenic activities are involved in numerous health impairments and may therefore select for detoxification mechanisms or a higher tolerance. Melanin, responsible for the black and red colourations of teguments, plays a role in metal ion chelation and its synthesis is positively linked to immunity, antioxidant capacity and stress resistance due to pleiotropic effects. Therefore, we expected darker birds to (1) store higher amounts of metals in their feathers, (2) maintain lower metal concentrations in blood and (3) suffer less from metal exposure. We exposed feral pigeons (Columba livia) exhibiting various plumage darkness levels to low, but chronic, concentrations of zinc and/or lead, two of the most abundant metals in urban areas. First, we found negative and positive effects of lead and zinc, respectively, on birds' condition and reproductive parameters. Then, we observed positive relationships between plumage darkness and both zinc and lead concentrations in feathers. Interestingly, though darker adults did not maintain lower metal concentrations in blood and did not have higher fitness parameters, darker juveniles exhibited a higher survival rate than paler ones when exposed to lead. Our results show that melanin-based plumage colouration does modulate lead effects on birds' fitness parameters but that the relationship between metals, melanin, and fitness is more complex than expected and thus stress the need for more studies. PMID- 27282323 TI - Tree-mycorrhizal associations detected remotely from canopy spectral properties. AB - A central challenge in global ecology is the identification of key functional processes in ecosystems that scale, but do not require, data for individual species across landscapes. Given that nearly all tree species form symbiotic relationships with one of two types of mycorrhizal fungi - arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) fungi - and that AM- and ECM-dominated forests often have distinct nutrient economies, the detection and mapping of mycorrhizae over large areas could provide valuable insights about fundamental ecosystem processes such as nutrient cycling, species interactions, and overall forest productivity. We explored remotely sensed tree canopy spectral properties to detect underlying mycorrhizal association across a gradient of AM- and ECM dominated forest plots. Statistical mining of reflectance and reflectance derivatives across moderate/high-resolution Landsat data revealed distinctly unique phenological signals that differentiated AM and ECM associations. This approach was trained and validated against measurements of tree species and mycorrhizal association across ~130 000 trees throughout the temperate United States. We were able to predict 77% of the variation in mycorrhizal association distribution within the forest plots (P < 0.001). The implications for this work move us toward mapping mycorrhizal association globally and advancing our understanding of biogeochemical cycling and other ecosystem processes. PMID- 27282324 TI - Estimating tissue-specific discrimination factors and turnover rates of stable isotopes of nitrogen and carbon in the smallnose fanskate Sympterygia bonapartii (Rajidae). AB - This study aimed to estimate trophic discrimination factors (TDFs) and metabolic turnover rates of nitrogen and carbon stable isotopes in blood and muscle of the smallnose fanskate Sympterygia bonapartii by feeding six adult individuals, maintained in captivity, with a constant diet for 365 days. TDFs were estimated as the difference between delta(13) C or delta(15) N values of the food and the tissues of S. bonapartii after they had reached equilibrium with their diet. The duration of the experiment was enough to reach the equilibrium condition in blood for both elements (estimated time to reach 95% of turnover: C t95%blood = 150 days, N t95%blood = 290 days), whilst turnover rates could not be estimated for muscle because of variation among samples. Estimates of Delta(13) C and Delta(15) N values in blood and muscle using all individuals were Delta(13) Cblood = 1.70/00, Delta(13) Cmuscle = 1.30/00, Delta(15) Nblood = 2.50/00 and Delta(15) Nmuscle = 1.50/00, but there was evidence of differences of c.0.40/00 in the Delta(13) C values between sexes. The present values for TDFs and turnover rates constitute the first evidence for dietary switching in batoids based on long-term controlled feeding experiments. Overall, the results showed that S. bonapartii has relatively low turnover rates and isotopic measurements would not track seasonal movements adequately. The estimated Delta(13) C values in S. bonapartii blood and muscle were similar to previous estimations for elasmobranchs and to generally accepted values in bony fishes (Delta(13) C = 1.50/00). For Delta(15) N, the results were similar to published reports for blood but smaller than reports for muscle and notably smaller than the typical values used to estimate trophic position (Delta(15) N c. 3.40/00). Thus, trophic position estimations for elasmobranchs based on typical Delta(15) N values could lead to underestimates of actual trophic positions. Finally, the evidence of differences in TDFs between sexes reveals a need for more targeted research. PMID- 27282325 TI - [Outpatient thoracic surgery: Evolution of the indications, current applications and limits]. AB - The objectives of outpatient surgery are to reduce the risks connected to hospitalization, to improve postoperative recovery and to decrease the health costs. Few studies have been performed in the field of thoracic surgery and there remains great scope for progress in outpatient lung surgery. The purpose of this article is to present a revue of the current situation and the prospects for the development of out patient thoracic surgery. PMID- 27282327 TI - [Smoking cessation support among persons in situation of precariousness]. AB - INTRODUCTION: Underprivileged people smoke more frequently, present with a more severe smoking profile and stop less often than wealthier smokers. They can have difficulties to afford smoking cessation treatments as the French medical insurance coverage system requires smokers to pay it in advance with a later reimbursement. The objective of this study was to compare the characteristics, treatment plans and cessation rates of smokers from disadvantaged population in comparison with smokers in wealthier condition. METHODS: Study population concerned smokers received for a first visit in the smoking cessation service at Georges-Pompidou European Hospital (Paris, France) in 2013. The EPICES score was used to define precariousness. The national file of smoking cessation consultation (CDT) was completed and the nicotine replacement therapy (NRT) prescriptions were detailed, as treatment could be given for free to precarious smokers on a weekly basis. Data were registered in CDTnet, the French national database of smoking cessation services. RESULTS: Precarious smokers (36.8%) presented with a more severe smoking profile and suffered more often from psychiatric disorders than wealthier smokers. They benefited most often from a combination NRT with patch and oral forms. The followed-up precarious smokers attended a greater number of consultations (4.7 against 3.4) and, if they were less often abstainers (22.2% against 41.3%), they were able to significantly reduce their consumption. CONCLUSIONS: Precarious smokers adhere to structured care with aid for access to TSN with a positive consequent impact on consumption. PMID- 27282326 TI - [Breast metastases from lung cancers with the EGFR mutation]. AB - INTRODUCTION: The breast is a rare site for metastases from lung cancers. Their occurrence in patients with adenocarcinoma which has the EGFR mutation is exceptional. In this context, it is sometimes difficult to differentiate a second primary breast cancer from a breast metastasis. OBSERVATIONS: We report the cases of two patients who developed breast metastases from lung adenocarcinoma that was TTF1 positive with a deletion of exon 19 of the EGFR gene. A non-smoking woman of Asian origin, presented with a solitary breast metastasis 29 months after being established on first-line chemotherapy. The second case was a Caucasian patient who was an active smoker presented with tumor progression with multiple metastases including involvement of both breasts 10 months after the start of treatment with a tyrosine kinase inhibitor. In both, tumor cells from the breast showed positive immunostaining for TTF1 and genotyping detected the presence of the deletion of exon 19 of the EGFR gene. CONCLUSION: In patients with lung adenocarcinoma and EGFR mutation, immunohistochemical examination, including TTF1 and genotyping of synchronous breast tumour, is needed to confirm its metastatic nature and to guide treatment. PMID- 27282328 TI - Sarcopenic Obesity in Adults With Spinal Cord Injury: A Cross-Sectional Study. AB - OBJECTIVES: To describe (1) the frequency and utility of clinically relevant spinal cord injury (SCI)-specific and general population thresholds for obesity and sarcopenic obesity; and (2) the fat and lean soft tissue distributions based on the neurologic level of injury and the American Spinal Injury Association Impairment Scale. DESIGN: Cross-sectional. SETTING: Tertiary SCI rehabilitation hospital. PARTICIPANTS: Persons (N=136; men, n=100; women, n=36) with chronic (mean +/- SD: 15.6+/-11.3y postinjury) tetraplegia (n=66) or paraplegia (n=70). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Body composition was assessed with anthropometrics and whole-body dual-energy x-ray absorptiometry. Muscle atrophy was quantified using a sarcopenia threshold of appendicular lean mass index (ALMI) (men, <=7.26kg/m2; women, <=5.5kg/m2). Obesity was defined by percentage body fat (men, >=25%; women, >=35%), visceral adipose tissue (>=130cm2), and SCI-specific obesity thresholds (body mass index [BMI] >=22kg/m2; waist circumference >=94cm). Sarcopenic obesity was defined as the presence of both sarcopenia and obesity. Groups were compared based on impairment characteristics using an analysis of covariance. RESULTS: Sarcopenic obesity was prevalent in 41.9% of the sample. ALMI was lower among participants with motor complete (6.2+/-1.3kg/m2) versus motor-incomplete (7.5+/-1.6kg/m2) injuries (P<.01). Whole-body fat was greater among participants with tetraplegia (28.8+/ 11.2kg) versus paraplegia (24.1+/-8.7kg; P<.05). Compared with general population guidelines (20.6%), SCI-specific BMI thresholds identified all the participants with obesity (77.9%) based on percentage body fat (72.1%). CONCLUSIONS: The observed frequency of sarcopenic obesity in this sample of individuals with chronic SCI is very high, and identification of obesity is dissimilar when using SCI-specific versus general population criteria. PMID- 27282329 TI - Optimizing the Management of Disabling Spasticity Following Spinal Cord Damage: The Ability Network-An International Initiative. AB - Optimizing the treatment of disabling spasticity in persons with spinal cord damage is hampered by a lack of consensus regarding the use of acceptable definitions of spasticity and disabling spasticity, and the relative absence of decision tools such as clinical guidelines and concise algorithms to support decision-making within the broader clinical community. Many people with spinal cord damage are managed outside specialist centers, and variations in practice result in unequal access to best practice despite equal need. In order to address these issues, the Ability Network-an international panel of clinical experts-was initiated to develop management algorithms to guide and standardize the assessment, treatment, and evaluation of outcomes of persons with spinal cord damage and disabling spasticity. To achieve this, consensus was sought on common definitions through facilitated, in-person meetings. To guide patient selection, an in-depth review of the available tools was performed and expert consensus sought to develop an appropriate instrument. Literature reviews are guiding the selection and development of tools to evaluate treatment outcomes (body functions, activity, participation, quality of life) as perceived by people with spinal cord damage and disabling spasticity, and their caregivers and clinicians. Using this approach, the Ability Network aims to facilitate treatment decisions that take into account the following: the impact of disabling spasticity on health status, patient preferences, treatment goals, tolerance for adverse events, and in cases of totally dependent persons, caregiver burden. PMID- 27282330 TI - Association between body mass index and outcomes in Japanese living kidney transplant recipients: The role of sex differences. AB - OBJECTIVE: To evaluate the impact of pretransplant body mass index on graft failure and mortality in Japanese patients undergoing living kidney transplant. METHODS: A cohort of 888 living kidney transplant recipients who received standard immunosuppressive therapy between 2000 and 2013 were identified from the Japan Academic Consortium of Kidney Transplantation database. Pretransplant body mass index was divided into three categories according to the following tertiles: <19.4, 19.5-22.2 and >=22.3 kg/m(2) . A multivariable time-to-event analysis was carried out. RESULTS: Estimated hazard ratios of the body mass index effects regarding graft failure were 1.62 (95% confidence interval 0.83-3.18) for the first tertile and 2.20 (95% confidence interval 1.24-3.90) for the third tertile. Patient mortality was 1.21 (95% confidence interval 0.32-4.54) for the first tertile and 1.52 (95% confidence interval 0.56-4.13) for the third tertile. In a subgroup analysis, the effects of body mass index according to sex were substantially heterogeneous (P = 0.029 for interaction). Pretransplant body mass index had a non-linear J-shaped association with graft failure that resulted from qualitative interaction between body mass index and the recipient's sex. CONCLUSIONS: Sex differences and interaction effects must be considered when evaluating the effects of pretransplant body mass index on post-transplant outcomes in Japanese patients undergoing living kidney transplant. PMID- 27282331 TI - Effects of signaled and unsignaled alternative reinforcement on persistence and relapse in children and pigeons. AB - Three experiments explored the impact of different reinforcer rates for alternative behavior (DRA) on the suppression and post-DRA relapse of target behavior, and the persistence of alternative behavior. All experiments arranged baseline, intervention with extinction of target behavior concurrently with DRA, and post-treatment tests of resurgence or reinstatement, in two- or three component multiple schedules. Experiment 1, with pigeons, arranged high or low baseline reinforcer rates; both rich and lean DRA schedules reduced target behavior to low levels. When DRA was discontinued, the magnitude of relapse depended on both baseline reinforcer rate and the rate of DRA. Experiment 2, with children exhibiting problem behaviors, arranged an intermediate baseline reinforcer rate and rich or lean signaled DRA. During treatment, both rich and lean DRA rapidly reduced problem behavior to low levels, but post-treatment relapse was generally greater in the DRA-rich than the DRA-lean component. Experiment 3, with pigeons, repeated the low-baseline condition of Experiment 1 with signaled DRA as in Experiment 2. Target behavior decreased to intermediate levels in both DRA-rich and DRA-lean components. Relapse, when it occurred, was directly related to DRA reinforcer rate as in Experiment 2. The post-treatment persistence of alternative behavior was greater in the DRA-rich component in Experiment 1, whereas it was the same or greater in the signaled-DRA-lean component in Experiments 2 and 3. Thus, infrequent signaled DRA may be optimal for effective clinical treatment. PMID- 27282332 TI - Small RNA and degradome profiling reveals important roles for microRNAs and their targets in tea plant response to drought stress. AB - Tea (Camellia sinensis) is a popular beverage worldwide. Drought stress (DS) is a major constraint on the growth, yield and quality of tea plants. MicroRNAs (miRNAs) play important roles in plant responses to DS. We constructed eight small RNA libraries from the drought-tolerant 'Ningzhou 2' (NZ2) and drought susceptible 'Zhuyeqi' (ZYQ) cultivars during four stages [control (CK), the fourth day of DS, the eighth day of DS and after recovery (RC)]. A total of 268 conserved and 62 novel miRNAs were identified using small RNA sequencing. In total, 139 (52.9%) and 96 (36.0%) conserved miRNAs were differentially expressed during the four stages (P <= 0.05) in NZ2 and ZYQ, respectively. A total of 814 predicted target genes were identified as differentially regulated by 199 miRNAs through degradome sequencing. Among them, 201 and 218 genes were specific to the NZ2 and ZYQ cultivars, respectively, and 395 were common to both cultivars. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed the biological roles of these targets and showed that some of the targets responded to DS in a stress- and cultivar-dependent manner. Correlated expression patterns between miRNA and their targets showed that specific miRNAs target the miRNA effector Argonaute 1 (AGO1), drought signaling-related receptors and enzymes, transcription factors, and other structural and functional proteins. The predicted regulatory networks provide insights into a potential miRNA mediated regulatory mechanism. These results will contribute to the breeding of drought-tolerant tea plants and to elucidating miRNA regulation in response to drought. PMID- 27282334 TI - Stenting of the Brachiocephalic Vein Following Occlusion After Coronary Artery Bypass Surgery. AB - We describe a case of left arm swelling over nine months post coronary artery bypass grafting (CABG), due to occlusion of the left brachiocephalic vein. The patient's perioperative course, diagnosis, and management of this complication are presented. doi: 10.1111/jocs.12765 (J Card Surg 2016;31:432-434). PMID- 27282333 TI - Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence. AB - pH regulates gene expression, biochemical activities and cellular behaviors. A mildly acidic pH activates the master virulence regulatory system PhoP/PhoQ in the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. The sensor PhoQ harbors an extracytoplasmic domain implicated in signal sensing, and a cytoplasmic domain controlling activation of the regulator PhoP. We now report that, surprisingly, a decrease in Salmonella's own cytoplasmic pH induces transcription of PhoP-activated genes even when the extracytoplasmic pH remains neutral. Amino acid substitutions in PhoQ's cytoplasmic domain hindered activation by acidic pH and attenuated virulence in mice, but did not abolish activation by low Mg(2+) or the antimicrobial peptide C18G. Conversely, removal of PhoQ's extracytoplasmic domains prevented the response to the latter PhoQ activating signals but not to acidic pH. PhoP-dependent genes were minimally induced by acidic pH in the non-pathogenic species Salmonella bongori but were activated by low Mg(2+) and C18G as in pathogenic S. enterica. Our findings indicate that the sensor PhoQ enables S. enterica to respond to both host- and bacterial-derived signals that alter its cytoplasmic pH. PMID- 27282335 TI - Role of laccase in the virulence of Talaromyces marneffei: A common link between AIDS-related fungal pathogens? PMID- 27282336 TI - Poly-l-Lactic Acid Nanofiber-Polyamidoamine Hydrogel Composites: Preparation, Properties, and Preliminary Evaluation as Scaffolds for Human Pluripotent Stem Cell Culturing. AB - Electrospun poly-l-lactic acid (PLLA) nanofiber mats carrying surface amine groups, previously introduced by nitrogen atmospheric pressure nonequilibrium plasma, are embedded into aqueous solutions of oligomeric acrylamide-end capped AGMA1, a biocompatible polyamidoamine with arg-gly-asp (RGD)-reminiscent repeating units. The resultant mixture is finally cured giving PLLA-AGMA1 hydrogel composites that absorb large amounts of water and, in the swollen state, are translucent, soft, and pliable, yet as strong as the parent PLLA mat. They do not split apart from each other when swollen in water and remain highly flexible and resistant, since the hydrogel portion is covalently grafted onto the PLLA nanofibers via the addition reaction of the surface amine groups to a part of the terminal acrylic double bonds of AGMA1 oligomers. Preliminary tested as scaffolds, the composites prove capable of maintaining short-term undifferentiated cultures of human pluripotent stem cells in feeder-free conditions. PMID- 27282337 TI - How many Layers has the Adventitia? - Structure of the Arterial Tunica Externa Revisited. AB - Tunica adventitia or tunica externa is the outer layer of the blood vessel wall. It consists of connective tissue with vasa and nervi vasorum and plays a key role in vascular health. The aim of our study was to compare the wall layers beyond tunica media in arteries of different type and location. The following arteries of pig, dog and cat were processed histologically and analysed by light microscopy: aorta ascendens, arcus aortae, aorta thoracica, aorta abdominalis, arteria (a.) femoralis, a. tibialis cranialis, a. carotis communis, a. lingualis, a. basilaris, a. cerebralis media, a. testicularis and aa. jejunales. We found two layers of connective tissue outside the media: (1) a compact layer with many elastic fibres in muscular and few in elastic arteries and (2) an outer layer of loose connective tissue. The compact layer was missing in aorta ascendens, arcus aortae and intracranial vessels. Adventitial stripping removed only the loose connective tissue layer. In spite of the still present compact layer, stripped arteries were very flimsy. We suggest using the term 'tunica externa' for the compact connective tissue layer and 'tunica adventitia' for the outermost loose connective tissue layer as in other organs. The presence of the tunica externa differs between species, arteries and arterial side, as well as the removability of tunica adventitia and tunica externa by anatomical dissection. PMID- 27282339 TI - Corrigendum to "Ozonation of chlortetracycline in the aqueous phase: Degradation intermediates and pathway confirmed by NMR" [Chemosphere 152 (2016) 31-38]. PMID- 27282338 TI - Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages. AB - Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-gamma most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis. PMID- 27282341 TI - Right Colectomy for Cancer: A Matched Comparison of Three Different Surgical Approaches. AB - PURPOSE: The standard approach to right colon cancer resection is still a matter of debate and includes laparoscopy, open midline incision, or open transverse incision. We aimed this study to compare the short- and long-term results of laparoscopic right-colectomy with those provided by the open approaches. METHODS: Of the 176 patients who underwent right-colectomy at our Department for nonmetastatic colon cancer, 40 patients treated by laparoscopy, 40 treated by transverse incisions, and 40 treated by midline incisions were selected and matched using the propensity score method. Short-term results included: operating time, morbidity rate, number of lymph-nodes harvested (LNH), patients' recovery features, and costs. Long-term results included: disease-specific survivals and the rate of incisional hernias. The sub-groups were compared using t-test and Chi square tests, whereas the Kaplan-Meier method was used to assess survivals. RESULTS: Laparoscopies were the longer procedures, providing similar morbidity rates and LNH in comparison with the open approaches. Laparoscopy provided a faster return to oral intake and a shorter use of analgesics comparing with the midline approach; however, it showed only a minor consumption of analgesics in comparison with transverse laparotomy. There were no differences in the hospital stay and the long-term results were comparable between sub-groups. Costs analysis documented minor but not significant surgical expenses for the transverse approach. CONCLUSIONS: Laparoscopy was documented safe, with similar morbidity rates and long-term results comparing with open surgery. Laparoscopy provided better functional short-term results comparing with the midline approach, but only small differences with respect to the transverse incision approach. PMID- 27282342 TI - End-tidal CO2 to detect recovery of spontaneous circulation during cardiopulmonary resuscitation: We are not ready yet. PMID- 27282343 TI - Optimizing quality of digital mammographic imaging using Taguchi analysis with an ACR accreditation phantom. AB - This work demonstrated the improvement of the visualization of lesions by modulating the factors of an X-ray mammography imaging system using Taguchi analysis. Optimal combinations of X-ray operating factors in each group of level combination were determined using the Taguchi method, in which all factors were organized into only 18 groups, yielding analytical results with the same confidence as if each factor had been examined independently. The 4 considered operating factors of the X-ray machine were (1) anode material (target), (2) kVp, (3) mAs and (4) field of view (FOV). Each of these factors had 2 or 3 levels. Therefore, 54 (2*3*3*3 = 54) combinations were generated. The optimal settings were Rh as the target, 28 kVp, 80 mAs and 19*23 cm(2) FOV. The grade of exposed mammographic phantom image increased from the automatic exposure control (AEC) setting 70.92 to 72.00 under the optimal setting, meeting the minimum standard (70.00) set by Taiwan's Department of Health. The average glandular dose (AGD) of the exposed phantom, 0.182 cGy, was lower than that, 0.203 cGy, under the AEC setting. The Taguchi method was extremely promising for the design of imaging protocols in clinical diagnosis. PMID- 27282344 TI - Psychoneuroimmunology and the Skin. AB - The nervous, immune, endocrine and integumentary systems are closely related and interact in a number of normal and pathological conditions. Nervous system mediators may bring about direct changes to the skin or may induce the release of immunological or hormonal mediators that cause pathological changes to the skin. This article reviews the psychological mechanisms involved in the development of skin diseases. PMID- 27282340 TI - Comparative transcriptomic analysis of human and Drosophila extracellular vesicles. AB - Extracellular vesicles (EVs) are membrane-enclosed nanoparticles containing specific repertoires of genetic material. In mammals, EVs can mediate the horizontal transfer of various cargos and signaling molecules, notably miRNA and mRNA species. Whether this form of intercellular communication prevails in other metazoans remains unclear. Here, we report the first parallel comparative morphologic and transcriptomic characterization of EVs from Drosophila and human cellular models. Electronic microscopy revealed that human and Drosophila cells release similar EVs with diameters ranging from 30 to 200 nm, which contain complex populations of transcripts. RNA-seq identified abundant ribosomal RNAs, related pseudogenes and retrotransposons in human and Drosophila EVs. Vault RNAs and Y RNAs abounded in human samples, whereas small nucleolar RNAs involved in pseudouridylation were most prevalent in Drosophila EVs. Numerous mRNAs were identified, largely consisting of exonic sequences displaying full-length read coverage and enriched for translation and electronic transport chain functions. By analogy with human systems, these sizeable similarities suggest that EVs could potentially enable RNA-mediated intercellular communication in Drosophila. PMID- 27282345 TI - In vitro and in vivo evaluation of puerarin-loaded PEGylated mesoporous silica nanoparticles. AB - Puerarin, which is extracted from Chinese medicine, is widely used in China and mainly used as a therapeutic agent for the treatment of cardiovascular diseases. Owing to its short elimination half-life in human beings, frequently intravenous administration of high doses of puerarin may be needed, which possibly leads to severe and acute side effects. The development of an effective sustained-release drug delivery system is urgently needed. In this study, PEGylated mesoporous silica nanoparticles (PEG-MSNs) had become a preferred way to prolong the half life and improve the bioavailability of drugs. The release of puerarin from PEG MSNs was pH dependent, and the release rate was much faster at lower pH than that at higher pH. Moreover, the PEG-MSNs exhibited improved blood compatibility over the MSNs in terms of low hemolysis, and it could also reduce the side effect of hemolysis induced by PUE. Compared with puerarin, PUE-loaded PEG-MSNs showed a 2.3-fold increase in half-life of puerarin and a 1.47-fold increase in bioavailability. Thus, the PEG-MSNs hold the substantial potential to be further developed as an effective sustained-release drug delivery system. PMID- 27282346 TI - RBANS memory percentage retention: No evidence of incremental validity beyond RBANS scores for diagnostic classification of mild cognitive impairment and dementia and for prediction of daily function. AB - RBANS percentage retention scores may be useful for diagnosis, but their incremental validity is unclear. Percentage retention versus RBANS immediate and delayed memory subtests and delayed index scores were compared for diagnostic classification and for prediction of function. Data from 173 memory clinic patients with an interdisciplinary diagnosis (no cognitive impairment, amnestic mild cognitive impairment [aMCI], and dementia due to Alzheimer's disease [AD]) and complete RBANS data were analyzed. Across diagnostic contrasts, list percentage retention classification accuracy was similar to List Learning delayed recall, but below the Delayed Memory Index (DMI). Similarly, for classifying no cognitive impairment versus aMCI or dementia due to AD, story percentage retention was similar to Story Memory subtests and below the DMI. For classifying aMCI versus AD; however, Story Memory exceeded the DMI, but was similar to Story Memory subtest scores. Similarly, for prediction of function percentage retention measures did not predict variance beyond that predicted by the RBANS subtest or index scores. In sum, there is no evidence that calculation of percentage retention for RBANS adds clinical utility beyond those provided by the standard RBANS scores. PMID- 27282347 TI - Interoccurrence time statistics in fully-developed turbulence. AB - Emergent extreme events are a key characteristic of complex dynamical systems. The main tool for detailed and deep understanding of their stochastic dynamics is the statistics of time intervals of extreme events. Analyzing extensive experimental data, we demonstrate that for the velocity time series of fully developed turbulent flows, generated by (i) a regular grid; (ii) a cylinder; (iii) a free jet of helium, and (iv) a free jet of air with the Taylor Reynolds numbers Relambda from 166 to 893, the interoccurrence time distributions P(tau) above a positive threshold Q in the inertial range is described by a universal q- exponential function, P(tau) = beta(2 - q)[1 - beta(1 - q)tau](1/(1-q)), which may be due to the superstatistical nature of the occurrence of extreme events. Our analysis provides a universal description of extreme events in turbulent flows. PMID- 27282348 TI - Integration of metal-organic frameworks into an electrochemical dielectric thin film for electronic applications. AB - The integration of porous metal-organic frameworks onto the surface of materials, for use as functional devices, is currently emerging as a promising approach for gas sensing and flexible displays. However, research focused on potential applications in electronic devices is in its infancy. Here we present a facile strategy by which interpenetrated, crystalline metal-organic framework films are deposited onto conductive metal-plate anodes via in situ temperature-controlled electrochemical assembly. The nanostructure of the surface as well as the thickness and uniformity of the film are well controlled. More importantly, the resulting films exhibit enhanced dielectric properties compared to traditional inorganic or organic gate dielectrics. This study demonstrates the successful implementation of the rational design of metal-organic framework thin films on conductive supports with high-performance dielectric properties. PMID- 27282349 TI - Functional coordination of muscles underlying changes in behavioural dynamics. AB - The dynamical systems approach addresses Bernstein's degrees of freedom problem by assuming that the neuro-musculo-skeletal system transiently assembles and dismantles its components into functional units (or synergies) to meet task demands. Strikingly, little is known from a dynamical point of view about the functioning of the muscular sub-system in this process. To investigate the interaction between the dynamical organisation at muscular and behavioural levels, we searched for specific signatures of a phase transition in muscular coordination when a transition is displayed at the behavioural level. Our results provide evidence that, during Fitts' task when behaviour switches to a different dynamical regime, muscular activation displays typical signatures of a phase transition; a reorganisation in muscular coordination patterns accompanied by a peak in the variability of muscle activation. This suggests that consistent changes occur in coordination processes across the different levels of description (i.e., behaviour and muscles). Specifically, in Fitts' task, target size acts as a control parameter that induces a destabilisation and a reorganisation of coordination patterns at different levels of the neuro-musculo skeletal system. PMID- 27282350 TI - Effects of Leisure-Time Physical Activity on Vertebral Dimensions in the Northern Finland Birth Cohort 1966. AB - Vertebral fractures are a common burden amongst elderly and late middle aged people. Vertebral cross-sectional area (CSA) is a major determinant of vertebral strength and thus associated with vertebral fracture risk. Previous studies suggest that physical activity affects vertebral CSA. We aimed to investigate the relationship between leisure-time physical activity (LTPA) from adolescence to middle age and vertebral dimensions in adulthood. We utilized the Northern Finland Birth Cohort 1966, of which 1188 subjects had records of LTPA at 14, 31 and 46 years, and had undergone lumbar magnetic resonance imaging (MRI) at the mean age of 47 years. Using MRI data, we measured eight dimensions of the L4 vertebra. Socioeconomic status, smoking habits, height and weight were also recorded at 14, 31 and 46 years. We obtained lifetime LTPA (14-46 years of age) trajectories using latent class analysis, which resulted in three categories (active, moderately active, inactive) in both genders. Linear regression analysis was used to analyze the association between LTPA and vertebral CSA with adjustments for vertebral height, BMI, socioeconomic status and smoking. High lifetime LTPA was associated with larger vertebral CSA in women but not men. Further research is needed to investigate the factors behind the observed gender related differences. PMID- 27282351 TI - The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes. AB - In 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the 'oncocytic subtype' of intraductal papillary mucinous neoplasm. Although several key molecular alterations of other intraductal papillary mucinous neoplasm subtypes have been discovered, including common mutations in KRAS, GNAS, and RNF3, those of oncocytic subtype have not been well characterized. We analyzed 11 pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms. Nine pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms uniformly exhibited typical entity-defining morphology of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent, nucleoli, and intraepithelial lumina. The remaining two were atypical. One lacked the arborizing papilla and had flat oncocytic epithelium only; the other one had focal oncocytic epithelium in a background of predominantly intestinal subtype intraductal papillary mucinous neoplasm. Different components of this case were analyzed separately. Formalin-fixed, paraffin-embedded specimens of all cases were microdissected and subjected to high-depth-targeted next-generation sequencing for a panel of 300 key cancer-associated genes in a platform that enabled the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Fresh frozen specimens of two cases were also subjected to whole-genome sequencing. For the nine typical pancreatic 'oncocytic subtype' of intraductal papillary mucinous neoplasms, the number of mutations per case, identified by next-generation sequencing, ranged from 1 to 10 (median=4). None of these cases had KRAS or GNAS mutations and only one had both RNF43 and PIK3R1 mutations. ARHGAP26, ASXL1, EPHA8, and ERBB4 genes were somatically altered in more than one of these typical 'oncocytic subtype' of intraductal papillary mucinous neoplasms but not in the other two atypical ones. In the neoplasm with flat oncocytic epithelium, the only mutated gene was KRAS. All components of the intestinal subtype intraductal papillary mucinous neoplasms with focal oncocytic epithelium manifested TP53, GNAS, and RNF43 mutations. In conclusion, this study elucidates that 'oncocytic subtype' of intraductal papillary mucinous neoplasm is not only morphologically distinct but also genetically distinct from other intraductal papillary mucinous neoplasm subtypes. Considering that now its biologic behavior is also being found to be different than other intraductal papillary mucinous neoplasm subtypes, 'oncocytic subtype' of intraductal papillary mucinous neoplasm warrants being recognized separately. PMID- 27282352 TI - Mammary analog secretory carcinoma of the thyroid gland: A primary thyroid adenocarcinoma harboring ETV6-NTRK3 fusion. AB - ETV6-NTRK3 fusion was identified in several cancers including the recently described mammary analog secretory carcinoma (MASC) of the salivary glands and a minority of papillary thyroid carcinomas. We describe three cases of primary MASC of the thyroid gland and provide a detailed clinical and pathological characterization of the tumor morphology, immunoprofile, and genetic background. Immunohistochemistry for PAX8, TTF-1, thyroglobulin, mammaglobin, GCDFP-15, S-100 protein, and p63 was used to define the tumor immunophenotype. Fluorescence in situ hybridization for ETV6 rearrangement was performed in three, and the next generation sequencing assay MSK-IMPACTTM (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) was performed in two cases. Primary MASC of the thyroid occurred in two women and one man, age 47-72 years. All patients presented with high T stage, infiltrative, locally aggressive tumors with extrathyroidal extension. Two cases were associated with well-differentiated papillary thyroid carcinoma. Histologically, they appeared as low-grade tumors, resembling MASC of the salivary glands and labeled positive for mammaglobin, GCDFP-15, S-100 protein, p63, weakly positive for PAX8, and negative for TTF-1 and thyroglobulin. Fluorescence in situ hybridization revealed ETV6 rearrangement in all cases. In two tested cases MSK-IMPACTTM confirmed the presence of ETV6 NTRK3 gene fusion. Two patients had at least two local recurrences, one was alive with disease, and one was alive and free of disease after 14 and 17 years, respectively. The third patient was alive and free of disease after 2 years. MASC of the thyroid is histologically, immunophenotypically, and genetically similar to its salivary gland counterpart. Thyroid MASC can be associated with a well differentiated papillary thyroid carcinoma component, supporting follicular cell origin. Clinically, these carcinomas may show frequent recurrences but are associated with long-term survival. Patients with MASC of the thyroid may potentially benefit from Trk molecular-targeted therapy. PMID- 27282354 TI - Market watch: Upcoming market catalysts in Q3 2016. PMID- 27282353 TI - Differential expression of enhancer of zeste homolog 2 (EZH2) protein in small cell and aggressive B-cell non-Hodgkin lymphomas and differential regulation of EZH2 expression by p-ERK1/2 and MYC in aggressive B-cell lymphomas. AB - EZH2, a member of the polycomb protein group, is an important methyltransferase that is overexpressed in various neoplasms. We found that in small cell B-cell lymphomas, EZH2 is expressed in <40% of neoplastic cells, with heterogenous signal intensity. In aggressive B-cell lymphomas, 70-100% of tumor cells were positive for EZH2 expression with high signal intensity, which correlated with a high proliferation rate. We investigated the potential signaling molecules that regulate EZH2 overexpression in aggressive B-cell lymphomas and found that 80% of cases of EZH2-positive diffuse large B-cell lymphoma show high p-ERK1/2 expression (average ~57% tumor cell positivity). In contrast, only a small percentage of tumor cells (~10%) show p-ERK1/2 expression in Burkitt lymphoma and double hit lymphoma. On average, 91 and 76% of neoplastic cells were positive for MYC expression in Burkitt lymphoma and double hit lymphoma, respectively, while only 20% neoplastic cells were positive for MYC expression in diffuse large B cell lymphoma. None of the aggressive B-cell lymphomas showed significant p-STAT3 expression in EZH2-overexpressed cases. The correlation of EZH2 expression with aggressive behavior and proliferation rate in B-cell neoplasms suggests that this molecule may function as an oncogenic protein in these neoplasms, with possible regulation by different signaling cascades in different types of aggressive B cell lymphomas: p-ERK-related signaling in diffuse large B-cell lymphoma, and MYC related signaling in Burkitt lymphoma and double hit lymphoma. Furthermore, EZH2 and associated signaling cascades may serve as therapeutic targets for the treatment of aggressive B-cell lymphomas. PMID- 27282355 TI - Azaepothilone B and its derivatives: a patent review. AB - INTRODUCTION: Azaepothilone B, also known as ixabepilone, is a semi synthetic second generation epothilone B analogue. Azaepothilone B, its derivatives, and analogues, are used for treating advance metastatic breast cancer. It has been used as a chemotherapeutic medication for cancer. AREAS COVERED: This review highlights the patents on different routes for synthesis of azaepothilone B, its derivatives and analogues. The review will also provide the reported pharmacological activity and its polymorphs in the treatment of several cancers, such as breast cancer (metastatic or locally advanced), non-Hodgkin's lymphoma, and pancreatic cancer. In addition, it considers other proliferative diseases such as viral infections, degenerative diseases of the musculoskeletal system, kidney disease, and immune response related diseases. Different databases such as Espacenet, ISI Web of Knowledge, Patbase, and Thomson Innovation have been searched extensively to review the patents. The analysis has been done to indicate the patenting trend across years and the comparison of active assignees. EXPERT OPINION: Azaepothilone B, along with its derivatives and analogues, can damage cancer cells in very low concentrations and retain its activity when tumor cells are insensitive to paclitaxel. Hence, it is highly potent agent. Azaepothilone B alone, in combination with other chemotherapeutics, or in the form of formulations, led to applications in various types of cancer. Also, antiproliferative activity of azaepothilone B has great potential for the treatment of proliferative diseases, such as skin diseases and infections. Recent progress in synthesizing azaepothilone B has encouraged researchers to develop new methods for the synthesis of azaepothilone B, its derivatives, and analogues, to obtain maximum yield in minimum steps. PMID- 27282356 TI - Prediction of residue-residue contact matrix for protein-protein interaction with Fisher score features and deep learning. AB - Protein-protein interactions play essential roles in many biological processes. Acquiring knowledge of the residue-residue contact information of two interacting proteins is not only helpful in annotating functions for proteins, but also critical for structure-based drug design. The prediction of the protein residue residue contact matrix of the interfacial regions is challenging. In this work, we introduced deep learning techniques (specifically, stacked autoencoders) to build deep neural network models to tackled the residue-residue contact prediction problem. In tandem with interaction profile Hidden Markov Models, which was used first to extract Fisher score features from protein sequences, stacked autoencoders were deployed to extract and learn hidden abstract features. The deep learning model showed significant improvement over the traditional machine learning model, Support Vector Machines (SVM), with the overall accuracy increased by 15% from 65.40% to 80.82%. We showed that the stacked autoencoders could extract novel features, which can be utilized by deep neural networks and other classifiers to enhance learning, out of the Fisher score features. It is further shown that deep neural networks have significant advantages over SVM in making use of the newly extracted features. PMID- 27282357 TI - Stalled replication fork rescue requires a novel DNA helicase. AB - During DNA replication, forks often stall and require restart. One mechanism for restart requires that the fork be moved in a direction opposite to that of replication. This reaction is known as fork regression. For this reaction to occur, the enzyme must couple unwinding of the nascent heteroduplex fork arms to the rewinding of nascent strands ahead of itself and to the parental duplex in its wake. As the arms of the fork are complementary, this reaction is isoenergetic making it challenging to study. To overcome this, a novel adaptation of magnetic tweezers was developed by the Croquette group. Here, a 1200bp hairpin was attached at opposite ends to a flow cell surface and a magnetic bead. By manipulating the bead with the magnets, force can be applied to unwind the hairpin or alternatively, released to allow the hairpin to rewind. This adaptation was used to study fork regression by RecG. The results show that this is an efficient regression enzyme, able to work against a large opposing force. Critically, it couples DNA unwinding to duplex rewinding and in the process, can displace bound proteins from fork arms. PMID- 27282358 TI - Metal [100] Nanowires with Negative Poisson's Ratio. AB - When materials are under stretching, occurrence of lateral contraction of materials is commonly observed. This is because Poisson's ratio, the quantity describes the relationship between a lateral strain and applied strain, is positive for nearly all materials. There are some reported structures and materials having negative Poisson's ratio. However, most of them are at macroscale, and reentrant structures and rigid rotating units are the main mechanisms for their negative Poisson's ratio behavior. Here, with numerical and theoretical evidence, we show that metal [100] nanowires with asymmetric cross sections such as rectangle or ellipse can exhibit negative Poisson's ratio behavior. Furthermore, the negative Poisson's ratio behavior can be further improved by introducing a hole inside the asymmetric nanowires. We show that the surface effect inducing the asymmetric stresses inside the nanowires is a main origin of the superior property. PMID- 27282360 TI - Corrigendum: Triggering mitophagy with far-red fluorescent photosensitizers. PMID- 27282359 TI - Determination of Anti-Adeno-Associated Viral Vector Neutralizing Antibodies in Patients With Heart Failure in the Cardiovascular Foundation of Colombia (ANVIAS): Study Protocol. AB - BACKGROUND: Recent progress in the pathophysiology of heart failure (HF) has led to the development of new therapeutic options such as gene therapy and the use of adeno-associated viral (AAV) vectors. Despite the promising results in early clinical trials of gene therapy for HF, various obstacles have been faced, such as the presence of neutralizing antibodies (NAbs) against the capsid vectors. NAb activity limits vector transduction levels and therefore diminishes the final therapeutic response. Recent studies evaluating the prevalence of NAbs in various populations found considerable geographic variability for each AAV serotype. However, the levels of NAbs in Latin American populations are unknown, becoming a limiting factor to conducting AAV vector therapeutic trials in this population. OBJECTIVE: The goal of this study is to determine for the first time, the prevalence of anti-AAV NAbs for the serotypes 1, 2, and 9 in HF patients from the city of Bucaramanga, Colombia, using the in vitro transduction inhibition assay. METHODS: We will conduct a cross-sectional study with patients who periodically attend the HF clinic of the Cardiovascular Foundation of Colombia and healthy volunteers matched for age and sex. For all participants, we will evaluate the NAb levels against serotypes AAV1, AAV2, and AAV9. We will determine NAb levels using the in vitro transduction inhibition assay. In addition, participants will answer a survey to evaluate their epidemiological and socioeconomic variables. Participation in the study will be voluntary and all participants will sign an informed consent document before any intervention. RESULTS: The project is in the first phase: elaboration of case report forms and the informed consent form, and design of the recruitment strategy. Patient recruitment is expected to begin in the spring of 2016. We expect to have preliminary results, including the titer of the viral vectors, multiplicity of infections that we will use for each serotype, and the general validation of the assay, at the end of 2016. The final results are expected mid-2017. CONCLUSIONS: This project is the first effort to evaluate NAb levels against AAV1, AAV2, and AAV9 serotypes in patients with HF in Latin America. Our results will allow us to check the cross-reactivity response between the serotypes assessed, to describe the epidemiological characteristics of the participant population, and to set up a link with earlier reports of NAb prevalence in the literature. PMID- 27282361 TI - Analysis of the incidence and factors predictive of inadvertent parathyroidectomy during thyroid surgery. AB - BACKGROUND: Inadvertent (or incidental) parathyroidectomy can occur during thyroidectomy. However, the factors associated with inadvertent parathyroidectomy remain unclear. This study aimed to report the rate of inadvertent parathyroidectomy during thyroidectomy and associated risk factors. METHODS: Variables including fine needle aspiration cytology findings, age, sex, thyroid weight, concurrent neck dissection, extent of thyroidectomy, and the presence of cancer and parathyroid tissue within the specimen were recorded for 266 patients. The incidence of post-operative hypocalcaemia was also recorded. Univariate and multivariate analysis were performed to identify factors associated with inadvertent parathyroidectomy. RESULTS: The inadvertent parathyroidectomy rate was 16 per cent. Univariate analysis revealed that cancer and concurrent neck dissection predicted inadvertent parathyroidectomy. On multivariate analysis, only concurrent neck dissection remained an independent predictor of inadvertent parathyroidectomy: it was associated with a fourfold increase in inadvertent parathyroidectomy. CONCLUSION: The inadvertent parathyroidectomy rate was 16 per cent and concurrent neck dissection was identified as an independent predictor of inadvertent parathyroidectomy. PMID- 27282362 TI - Efficacy and Safety of Antidepressants Added to Antipsychotics for Schizophrenia: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: The authors examined the safety and efficacy of antidepressants added to antipsychotic drugs in the treatment of schizophrenia. METHOD: Multiple databases and previous publications were searched through June 2015 to identify all randomized controlled trials of any add-on antidepressants compared with placebo or no-treatment in schizophrenia. Depressive and negative symptoms (primary outcomes), overall symptoms, positive symptoms, side effects, exacerbation of psychosis, and responder rates were examined. Subgroup, meta regression, and sensitivity analyses were performed, as well as investigations of publication bias and risk of bias. RESULTS: Eighty-two randomized controlled trials with a total of 3,608 participants were included. Add-on antidepressants appeared more efficacious than controls for depressive symptoms (standardized mean difference: -0.25, 95% CI=-0.38 to -0.12), negative symptoms (standardized mean difference: -0.30, 95% CI=-0.44 to -0.16), overall symptoms (standardized mean difference: -0.24, 95% CI=-0.39 to -0.09), positive symptoms (standardized mean difference: -0.17, 95% CI=-0.33 to -0.01), quality of life (standardized mean difference: -0.32, 95% CI=-0.57 to -0.06), and responder rate (risk ratio: 1.52, 95% CI=1.29 to 1.78; number-needed-to-treat-to-benefit: 5, 95% CI=4 to 7). The effects on depressive and negative symptoms appeared more pronounced when minimum thresholds of these symptoms were inclusion criteria (standardized mean difference: -0.34, 95% CI=-0.58 to -0.09 and standardized mean difference: -0.58, 95% CI=-0.94 to -0.21, respectively). There were no significant differences between antidepressants and controls in terms of exacerbation of psychosis, premature discontinuation, and the number of participants with at least one adverse event. More patients taking add-on antidepressants suffered from abdominal pain, constipation, dizziness, and dry mouth. CONCLUSIONS: Analysis of primary outcomes (depressive and negative symptoms) suggests small, beneficial effects of adjunctive antidepressants. It would appear that this augmentation can be accomplished with a low risk of exacerbation of psychosis and adverse effects. However, secondary and subgroup analyses should be interpreted cautiously and considered exploratory. PMID- 27282363 TI - Alkane-Metal Interfacial Structure and Elastic Properties by Molecular Dynamics Simulation. AB - The structure of amorphous materials near the interface with an ordered substrate can be affected by various characteristics of the adjoining phases, such as the lattice spacing of the adherent surface, polymer chain length, and adhesive strength. To discern the influence of each of these factors, four FCC metal lattices are examined for three chain lengths of n-alkane and van der Waals interfacial interactions are controlled by adjusting the Lennard-Jones 12-6 potential parameters. The role of interaction strength is investigated for a single chain length and substrate combination. Four nanoconfined systems are also analyzed in terms of their mechanical strength. A strong layering effect is observed near the interface for all systems. The distinctiveness of polymer layering, i.e., the maximum density and spatial extent, exhibits a logarithmic dependence on the interaction strength between polymer and substrate. Congruency with the substrate lattice parameter further enhances this effect. Moreover, the elastic modulus of the alkane phase as a function of layer thickness indicates that the effects of ordering within the structure extend beyond the immediately obvious interfacial region. PMID- 27282364 TI - Metal-Organic Framework Nodes Support Single-Site Magnesium-Alkyl Catalysts for Hydroboration and Hydroamination Reactions. AB - Here we present the first example of a single-site main group catalyst stabilized by a metal-organic framework (MOF) for organic transformations. The straightforward metalation of the secondary building units of a Zr-MOF with Me2Mg affords a highly active and reusable solid catalyst for hydroboration of carbonyls and imines and for hydroamination of aminopentenes. Impressively, the Mg-functionalized MOF displayed very high turnover numbers of up to 8.4 * 10(4) for ketone hydroboration and could be reused more than 10 times. MOFs can thus be used to develop novel main group solid catalysts for sustainable chemical synthesis. PMID- 27282365 TI - The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol. AB - RATIONALE: Some individuals are particularly responsive to reward-associated stimuli ("cues"), including the effects of these cues on craving and relapse to drug-seeking behavior. In the cases of nicotine and alcohol, cues may acquire these abilities via the incentive-enhancing properties of the drug. OBJECTIVES: To determine the interaction between cue-responsivity and nicotine reinforcement, we studied the patterns of nicotine self-administration in rats categorized based on their tendency to approach a food-predictive cue ("sign-trackers") or a reward delivery location ("goal-trackers"). In a second experiment, we determined whether nicotine and ethanol altered the incentive value of a food cue. METHODS: Rats were classified as sign- or goal-trackers during a Pavlovian conditioned approach paradigm. Rats then self-administered intravenous nicotine (0.03 mg/kg infusions) followed by extinction and cue-induced reinstatement tests. We also tested the effects of nicotine (0.4 mg/kg base s.c.) or ethanol (0.7 g/kg i.p.) on the approach to, and reinforcing efficacy of, a food cue. RESULTS: Sign trackers showed greater reinstatement in response to a nicotine cue. Further, nicotine enhanced sign-tracking but not goal-tracking to a food cue and also enhanced responding for the food cue during the conditioned reinforcement test. Conversely, ethanol reduced sign-tracking and increased goal-tracking, but had no effect on conditioned reinforcement. CONCLUSIONS: Our studies demonstrate that the tendency to attribute incentive value to a food cue predicts enhanced cue induced reinstatement. Additionally, the incentive value of food cues is differentially modulated by nicotine and ethanol, which may be related to the reinforcing effects of these drugs. PMID- 27282366 TI - Effect of the CYP2D6 and APOE Polymorphisms on the Efficacy of Donepezil in Patients with Alzheimer's Disease: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Differential responses to donepezil treatment in patients with Alzheimer's disease (AD) have been observed in clinical practice. It remains controversial whether, and to what extent, individual variation in the genes responsible for drug metabolism (CYP2D6) or those associated with AD pathogenesis (APOE) modulate the response to donepezil treatment. OBJECTIVE: The aim of this study was to better understand the potential link between donepezil treatment response and CYP2D6 or APOE polymorphisms. METHODS: We performed a meta-analysis based on data collected from 1266 donepezil-treated AD patients, and evaluated the association of CYP2D6 or APOE polymorphisms with treatment effectiveness. RESULTS: No significant difference was observed in the responder rate of donepezil treatment between the normal function CYP2D6 alleles group and the decreased/non-functional group [odds ratio (OR) 1.34, 95 % confidence interval (CI) 0.5-3.58; p = 0.56]. However, compared with the increased function CYP2D6 alleles group, the normal function group had a better response to donepezil treatment (OR 1.52, 95 % CI 1.14-2.03; p = 0.005). For the specific CYP2D6 single nucleotide polymorphism rs1080985, patients who carried the G allele had a significantly higher risk of poor response to donepezil treatment. After adjusting the data based on APOE genotype, it was observed that only individuals bearing both the APOE-epsilon4 allele and the rs1080985-G allele showed a significant increase in the frequency of treatment non-response (OR 1.73, 95 % CI 1.07-2.09; p = 0.03). No independent effect of APOE polymorphism on donepezil clinical responses was found (OR 1.08, 95 % CI 0.85-1.38; p = 0.53). Lastly, in a subgroup analysis based on ethnicity, all results remained consistent. CONCLUSION: The CYP2D6 genotype may be potentially effective for predicting the response to donepezil treatment in AD patients. PMID- 27282367 TI - Estimation of environmentally relevant chemical properties of veterinary ionophore antibiotics. AB - Monensin (MON) and salinomycin (SAL), known as polyether ionophore antibiotics (IPAs), are extensively used in livestock industry and can enter the environment via animal manure and agricultural runoff. Although some studies have investigated the environmental fate and transformation of IPAs, the lack of information on IPAs' aqueous-phase chemical properties is a major hindrance for further in-depth research. This study was able to experimentally determine the acidity constants (pKa), metal-complex dissociation constants (Kdiss), and intrinsic aqueous solubility of MON species, and some of these properties of SAL. The pKa value of MON was found to be 4.5, close to other aliphatic carboxylic acids and the predicted value by the computer program ChemAxon. The metal-complex dissociation constants of MON were estimated to be 0.058 and 0.573 with sodium ion (Na(+)) and potassium ion (K(+)), respectively. The Kdiss value of SAL with sodium ion was found to be 1.31. Compared to the previous values determined in organic solvents, the Kdiss of MON in aqueous phase are several orders of magnitude higher but maintain the same relative selectivity toward metal ions (Na(+) versus K(+)). The determined pKa and Kdiss values were also used to assess the aqueous solubility limits of different IPA species under different pH and metal ion concentrations. Results from this study provide more accurate information for the properties of IPAs. The obtained constants can be applied to predict the speciation of IPAs in various aquatic systems and help shed light on the environmental fate of IPAs. PMID- 27282368 TI - Effects of gamma-Fe2O3 nanoparticles on the survival and reproduction of Biomphalaria glabrata (Say, 1818) and their elimination from this benthic aquatic snail. AB - This study aims to evaluate the effects of maghemite nanoparticles (gamma-Fe2O3) coated with meso-2, 3-dimercaptosuccinic acid (DMSA) stabilizer on the survival and reproduction of the aquatic snail Biomphalaria glabrata. The cumulative means of egg masses and eggs per individual in the control group at the end of 4 weeks were 18.8 and 326.7, respectively. These values at the concentration of 1 mg/L were 17.2 and 291.6; at 10 mg/L, they were 19.6 and 334.4 ,and at 100 mg/L, they were 14.3 and 311.1. Results showed no significant differences between the tested and the control groups at the level of p < 0.05. Exposure of embryos for 10 days showed absence of mortality, malformation, or hatching delay. X-ray microtomography confirmed the presence of nanoparticles in exposed individuals and showed the complete elimination of the nanoparticles after 30 days in clean water. In the studied conditions, it is clear that gamma-Fe2O3 coated with stabilizing DMSA did not alter the fecundity or the fertility of the snail B. glabrata after 4 weeks of exposure, and accumulation was not present after 30 days in clean water. PMID- 27282369 TI - Ag/Ag2SO3 plasmonic catalysts with high activity and stability for CO2 reduction with water vapor under visible light. AB - The conversion of CO2 into useful raw materials for fuels and chemicals by solar energy is described using a plasmonic photocatalyst comprised of Ag supported on Ag2SO3 (Ag/Ag2SO3) fabricated by a facile solid-state ion-exchange method and subsequent reduction with hydrazine hydrate. The optimum molar ratio of Ag(0)/Ag(+) was 5 %. Visible light irradiation (>400 nm) of the Ag/Ag2SO3 powder in the presence of CO2 and water vapor led to the formation of CH4 and CO with a quantum yield of 0.126 %, and an energy returned on energy invested of 0.156 %. The Ag/Ag2SO3 retained high catalytic activity after ten successive experimental cycles. The catalysts were characterized using X-ray diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy with energy-dispersive X ray analysis, UV/Vis absorption spectroscopy, and Brunauer-Emmett-Teller analyses, as well as photocurrent action spectroscopy. It is proposed that the photocatalytic activity of the catalysts is initiated by energy conversion from incident photons to localized surface plasmon resonance oscillations of silver nanoparticles. This plasmonic energy is transferred to the Ag2SO3 by direct electron transfer and/or resonant energy transfer, causing the separation of photogenerated electron/hole pairs. PMID- 27282370 TI - Biological responses of midge (Chironomus riparius) and lamprey (Lampetra fluviatilis) larvae in ecotoxicity assessment of PCDD/F-, PCB- and Hg contaminated river sediments. AB - We evaluated the utility of chironomid and lamprey larval responses in ecotoxicity assessment of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/F)-, polychlorinated biphenyls (PCB)- and mercury (Hg)-contaminated river sediments. Sediment samples were collected from the River Kymijoki with a known industrial pollution gradient. Sediment for the controls and lamprey larvae were obtained from an uncontaminated river nearby. Contamination levels were verified with sediment and tissue PCDD/F, PCB and Hg analyses. Behaviour of sediment exposed chironomid and lamprey larvae were measured with Multispecies Freshwater Biomonitor(c) utilizing quadrupole impedance conversion technique. In addition, mortality, growth and head capsule deformity incidence of chironomids were used as ecotoxicity indicators. WHOPCDD/F+PCB-TEQ in the R. Kymijoki sediments ranged from the highest upstream 22.36 ng g(-1) dw to the lowest 1.50 ng g(-1) near the river mouth. The sum of PCDD/Fs and PCBs correlated strongly with Hg sediment concentrations, which ranged from <0.01 to 1.15 MUg g(-1). Lamprey tissue concentrations of PCDD/Fs were two orders and PCBs one order of magnitude higher in the R. Kymijoki compared to the reference. Chironomid growth decreased in contaminated sediments and was negatively related to sediment ?PCDD/Fs, WHOPCDD/F+PCB-TEQ and Hg. There were no significant differences in larval mortality or chironomid mentum deformity incidence between the sediment exposures. The distinct behavioural patterns of both species indicate overall applicability of behavioural MFB measurements of these species in sediment toxicity bioassays. Chironomids spent less and lampreys more time in locomotion in the most contaminated sediment compared to the reference, albeit statistically significant differences were not detected. Lamprey larvae had also a greater activity range in some of the contaminated sediments than in the reference. High pollutant levels in lamprey indicate risks for biomagnification in the food webs, with potential health risks to humans consuming fish. PMID- 27282372 TI - The environmental Kuznets curve and CO2 emissions in the USA : Is the relationship between GDP and CO2 emissions time varying? Evidence across economic sectors. AB - In this paper, we analyze the existence of the environmental Kuznets curve as reported by Kuznets (Am Econ Rev 5:1-28, 1955) by using the methodology proposed by Kejriwal and Perron (J Econ 146:59-73, 2008, J Bus Econ Stat 28:503-522, 2010) and applying Jaunky's (Energy Policy 39(3):1228-1240, 2011) specification using quarterly data from 1973:1 to 2015:2. We also allow different behaviors across time and identify it by economic sectors. Our results show the existence of the environmental Kuznets curve (EKC) in the USA only when we allow for structural breaks. Interestingly, the industrial sector shows a different pattern than do other economic sectors; with the beginning of the economic crisis, it appears to have abandoned the objective of the environmental stabilization found until then. PMID- 27282371 TI - Response of leaf and fine roots proteomes of Salix viminalis L. to growth on Cr rich tannery waste. AB - The tannery industry is a major source of anthropogenic chromium (Cr) contamination due to the large amounts of solid waste produced and its problematic management. The unique composition of tannery waste, usually high concentrations of Cr and other metals as well as organic matter and nutrients, makes it a great risk for soil and water environment but also a possible effective fertilizer for non-food plants that can tolerate metals. The goal of this study was to understand the adaptation mechanism of Salix viminalis to growth on Cr-rich tannery waste from an active landfill. We used a proteomic approach to identify leaf and fine roots proteins altered by tannery waste as compared to control soil conditions. We found no obvious symptoms of oxidative stress in leaves or fine roots. Proteomic results indicated some changes in metabolism, with increases in energy production processes and their greater efficiency for leaves rather than root development. Comparison between S. viminalis and P. * canescens response to tannery waste suggested that S. viminalis is not suitable for remediation of Cr-contaminated areas of a tannery waste landfill site. PMID- 27282373 TI - Morphological effect of BiVO4 catalysts on degradation of aqueous paracetamol under visible light irradiation. AB - Morphological effect of bismuth vanadate (BiVO4) on visible light-driven catalytic degradation of aqueous paracetamol was carefully investigated using four monoclinic BiVO4 catalysts. The catalysts with different morphologies were controllably prepared by a hydrothermal method without any additions. The prepared catalysts were fully characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV-Vis diffuse reflectance spectroscopy (DRS). Under the visible light irradiation, these catalysts with different morphology were investigated to degrade aqueous paracetamol contaminant. The degradation effects were evaluated based on the catalyst morphology, solution pH, initial paracetamol concentration, and catalyst dosage. Cube-like BiVO4 powders exhibited excellent photocatalytic performance. The optimal photocatalytic performance of the cube-like BiVO4 in degrading paracetamol was achieved. PMID- 27282374 TI - Clinical prediction model to identify vulnerable patients in ambulatory surgery: towards optimal medical decision-making. AB - BACKGROUND: Ambulatory surgery patients are at risk of adverse psychological outcomes such as anxiety, aggression, fatigue, and depression. We developed and validated a clinical prediction model to identify patients who were vulnerable to these psychological outcome parameters. METHODS: We prospectively assessed 383 mixed ambulatory surgery patients for psychological vulnerability, defined as the presence of anxiety (state/trait), aggression (state/trait), fatigue, and depression seven days after surgery. Three psychological vulnerability categories were considered-i.e., none, one, or multiple poor scores, defined as a score exceeding one standard deviation above the mean for each single outcome according to normative data. The following determinants were assessed preoperatively: sociodemographic (age, sex, level of education, employment status, marital status, having children, religion, nationality), medical (heart rate and body mass index), and psychological variables (self-esteem and self-efficacy), in addition to anxiety, aggression, fatigue, and depression. A prediction model was constructed using ordinal polytomous logistic regression analysis, and bootstrapping was applied for internal validation. The ordinal c-index (ORC) quantified the discriminative ability of the model, in addition to measures for overall model performance (Nagelkerke's R (2) ). RESULTS: In this population, 137 (36%) patients were identified as being psychologically vulnerable after surgery for at least one of the psychological outcomes. The most parsimonious and optimal prediction model combined sociodemographic variables (level of education, having children, and nationality) with psychological variables (trait anxiety, state/trait aggression, fatigue, and depression). Model performance was promising: R (2) = 30% and ORC = 0.76 after correction for optimism. CONCLUSION: This study identified a substantial group of vulnerable patients in ambulatory surgery. The proposed clinical prediction model could allow healthcare professionals the opportunity to identify vulnerable patients in ambulatory surgery, although additional modification and validation are needed. (ClinicalTrials.gov number, NCT01441843). PMID- 27282375 TI - Unintended effects of the herbicides 2,4-D and dicamba on lady beetles. AB - Weed resistance to glyphosate and development of new GM crops tolerant to 2,4 dichlorophenoxyacetic acid (2,4-D) and dicamba is expected to lead to increased use of these herbicides in cropland. The lady beetle, Coleomegilla maculata is an important beneficial insect in cropland that is commonly used as an indicator species in safety evaluations of pesticides. Here, we examined the lethal and non lethal effects of 2,4-D and dicamba active ingredients and commercial formulations to this lady beetle species, and tested for synergistic effects of the herbicides. Second instars of lady beetles were exposed to an experimental treatment, and their mortality, development, weight, sex ratio, fecundity, and mobility was evaluated. Using similar methods, a dose-response study was conducted on 2,4-D with and without dicamba. The commercial formulation of 2,4-D was highly lethal to lady beetle larvae; the LC90 of this herbicide was 13 % of the label rate. In this case, the "inactive" ingredients were a key driver of the toxicity. Dicamba active ingredient significantly increased lady beetle mortality and reduced their body weight. The commercial formulations of both herbicides reduced the proportion of males in the lady beetle population. The herbicides when used together did not act synergistically in their toxicity toward lady beetles versus when the chemistries were used independently. Our work shows that herbicide formulations can cause both lethal and sublethal effects on non-target, beneficial insects, and these effects are sometimes driven by the "inactive" ingredients. The field-level implications of shifts in weed management practices on insect management programs should receive further attention. PMID- 27282376 TI - Caveolin-1/-3: therapeutic targets for myocardial ischemia/reperfusion injury. AB - Myocardial ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality worldwide. Caveolae, caveolin-1 (Cav-1), and caveolin-3 (Cav-3) are essential for the protective effects of conditioning against myocardial I/R injury. Caveolins are membrane-bound scaffolding proteins that compartmentalize and modulate signal transduction. In this review, we introduce caveolae and caveolins and briefly describe the interactions of caveolins in the cardiovascular diseases. We also review the roles of Cav-1/-3 in protection against myocardial ischemia and I/R injury, and in conditioning. Finally, we suggest several potential research avenues that may be of interest to clinicians and basic scientists. The information included, herein, is potentially useful for the design of future studies and should advance the investigation of caveolins as therapeutic targets. PMID- 27282377 TI - Chest radiography in acute aortic syndrome: pearls and pitfalls. AB - Acute aortic syndrome is a group of life-threatening diseases of the thoracic aorta that usually present to the emergency department. It includes aortic dissection, aortic intramural hematoma, and penetrating aortic ulcer. Rare aortic pathologies of aorto-esophageal fistula and mycotic aneurysm may also be included in this list. All these conditions require urgent treatment with complex clinical care and management. Most patients who present with chest pain are evaluated with a chest radiograph in the emergency department. It is important that maximum diagnostic information is extracted from the chest radiograph as certain signs on the chest radiograph are extremely useful in pointing towards the diagnosis of acute aortic syndrome. PMID- 27282378 TI - Frustration Tolerance in Youth With ADHD. AB - OBJECTIVE: The objective of this study was to compare children with ADHD with children without ADHD on frustration tolerance and to examine the role of oppositional defiant disorder (ODD) in frustration tolerance within the sample. METHOD: Participants included 67 children ages 10 to 14 years-old with (n = 37) and without (n = 30) Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) ADHD who completed the Mirror Tracing Persistence Task (MTPT), a validated computerized behavioral measure of frustration tolerance. RESULTS: Children with ADHD were more likely to quit this task than children without ADHD, demonstrating lower levels of frustration tolerance. There were no differences in frustration tolerance between children with ADHD + ODD and those with ADHD - ODD. Moreover, ODD did not moderate the relationship between ADHD and frustration tolerance. CONCLUSION: Our results suggest that low frustration tolerance is directly linked to ADHD and not better accounted for by ODD. This research highlights specific behavioral correlates of frustration in children with ADHD. PMID- 27282379 TI - Comparative expression patterns and diagnostic efficacies of SR splicing factors and HNRNPA1 in gastric and colorectal cancer. AB - BACKGROUND: Serine/arginine-rich splicing factors (SRSFs) and HNRNPA1 have oncogenic properties. However, their proteomic expressions and practical priority in gastric cancer (GC) and colorectal cancer (CRC) are mostly unknown. To apply SFs in clinics, effective marker selection and characterization of properties in the target organ are essential. METHODS: We concurrently analyzed SRSF1, 3, and 5 7, and HNRNPA1, together with the conventional tumor marker carcinoembryonic antigen (CEA), in stomach and colorectal tissue samples (n = 420) using semiquantitative immunoblot, subcellular fractionation, and quantitative real time polymerase chain reaction methods. RESULTS: In the semiquantitative immunoblot analysis, HNRNPA1 and SRSF7 levels were significantly higher in GC than in gastric normal mucosa, and SRSF7 levels were higher in intestinal-type compared with diffuse-type of gastric adenocarcinoma. Of the SFs, only HNRNPA1 presented greater than 50 % upregulation (cancer/normal mucosa > 2-fold) incidences and CEA-comparable, acceptable (>70 %) detection accuracy (74 %) for GC. All SF protein levels were significantly higher in CRC than in colorectal normal mucosa, and HNRNPA1 levels were higher in low-stage CRC compared with high stage CRC. Among the SFs, HNRNPA1 and SRSF3 presented the two highest upregulation incidences (88 % and 74 %, respectively) and detection accuracy (90 % and 84 %, respectively) for CRC. The detection accuracy of HNRNPA1 was comparable to that of CEA in low (<= II)-stage CRC but was inferior to that of CEA in high (>II)-stage CRC. Extranuclear distributions of HNRNPA1 and SRSF6 (cytosol/microsome) differed from those of other SRSFs (membrane/organelle) in both cancers. In an analysis of the six SF mRNAs, all mRNAs presented unacceptable detection accuracies (<=70 %) in both cancers, and all mRNAs except SRSF6 were disproportionate to the corresponding protein levels in GC. CONCLUSION: Our results provide a comprehensive insight into the six SF expression profiles in GC and indicate that, among the SFs, HNRNPA1, but not HNRNPA1 mRNA, is the most effective, novel GC marker. Regardless of the good to excellent detection accuracy of SRSF3 and HNRNPA1 in CRC, the SFs have lower practical priority than CEA, especially for high-stage CRC detection. PMID- 27282381 TI - Understanding Non-Adherence From the Inside: Hypertensive Patients' Motivations for Adhering and Not Adhering. AB - Patients' low adherence to medical treatment in chronic illnesses is one of the biggest public health problems. Numerous studies attend to the diverse factors associated with patient adherence. However, little research has been done to explore patients' reasons for non-compliance from their own point of view. In this article, we aim to understand patient non-adherence using dialogical self theory and qualitative research methods. We interviewed 51 hypertensive patients to explore their anti- and pro-adherence motivations. Results show that most patients adhere and non-adhere to different aspects of treatment programs (medication, exercise, diet) according to the way they construct meaning to those activities. Also, our findings support the notion that patients' non-adherent behavior aims to preserve important values such as self-esteem, autonomy, affiliation, well-being, freedom, and health (or that more adherence is not worth the extra effort). We discuss the therapeutic relevance of empathically understanding patients' worldview and implicit beliefs. PMID- 27282380 TI - Finding covert fluid: methods for detecting volume overload in children on dialysis. AB - BACKGROUND: Lung ultrasound is a novel technique for detecting generalized fluid overload in children and adults with end-stage renal disease (ESRD). Echocardiography and bioimpedance spectroscopy are established methods, albeit variably adopted in clinical practice. We compared the practicality and accuracy of lung ultrasound with current objective techniques for detecting fluid overload in children with ESRD. METHODS: A prospective observational study was performed to compare lung ultrasound B-lines, echocardiographic measurement of inferior vena cava parameters and bioimpedance spectroscopy in the assessment of fluid overload in children with ESRD on dialysis. The utility of each technique in predicting fluid overload, based on short-term weight gain, was assessed. Multiple linear regression models to predict fluid overload by weight were explored. RESULTS: A total of 22 fluid assessments were performed in 13 children (8 on peritoneal dialysis, 5 on haemodialysis) with a median age of 4.0 (range 0.8-14.0) years. A significant linear correlation was observed between the number of B-lines detected by lung ultrasound and fluid overload by weight (r = 0.57, p = 0.005). A non-significant positive linear correlation was observed between fluid overload by weight and bioimpedance spectroscopy (r = 0.43, p = 0.2), systolic blood pressure (r = 0.19, p = 0.4) and physical examination measurements (r = 0.19, p = 0.4), while a non-significant negative linear relationship was found between the inferior vena cava collapsibility index and fluid overload by weight (r = -0.24, p = 0.3). In multiple linear regression models, a combination of three fluid parameters, namely lung ultrasound B-lines, clinical examination and systolic blood pressure, best predicted fluid overload (R 2 = 0.46, p = 0.05). CONCLUSIONS: Lung ultrasound may be superior to echocardiographic methods and bioimpedance spectroscopy in detecting volume overload in children with ESRD. Given the practicality and sensitivity of this new technique, it can be adopted alongside clinical examination and blood pressure in the routine assessment of fluid status in children with ESRD. PMID- 27282382 TI - Effect of adjuvant interferon therapy on hepatitis B virus-related hepatocellular carcinoma: a systematic review. AB - OBJECTIVE: The objective of this study is to evaluate the efficacy of adjuvant interferon therapy for hepatitis B virus-related hepatocellular carcinoma (HCC) after different previous therapy. METHODS: An electronic search for articles about adjuvant treatment with IFN for patients with HCC published between 2000 and 2015 was conducted in MEDLINE, PubMed, Cochrane Library, and EMBASE databases. All data was tested with Stata12.0 software. RESULTS: Six trials with a total of 1054 subjects were screened according to inclusion and exclusion standards. Five hundred and seventeen HCC patients were treated with adjuvant treatment with IFN and 537 patients with placebo. Compared to the control group, both the recurrence rate and death rate of HCC in IFN group were statistically lower, especially after transhepatic arterial chemotherapy and embolization (TACE) treatment and both TACE and resection according to subgroup analysis. There is no statistical significance on the both recurrence and death rate of HBV related hepatocellular carcinoma after surgical resection treatment (RR = 0.96, 95 % CI, 0.84 to 1.1, p = 0.59 for recurrence and RR = 0.78, 95 % CI, 0.60 to 1.04, p = 0.09 for death rates). CONCLUSIONS: Adjuvant IFN therapy may significantly reduced mortality as well as recurrence rate of patients with HBV related HCC after no matter what the previous treatment. On the other hand, there is no statistical significance on the recurrence rate and mortality after surgical resection only. More research is needed into the relationship between effect of adjuvant interferon therapy and previous therapy, especially TACE. PMID- 27282383 TI - Zinc in Multiple Sclerosis: A Systematic Review and Meta-Analysis. AB - In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS. Searching the databases PubMed and EMBASE as well as going through reference lists in included articles 24 studies were found measuring Zn in patients with MS. Of these, 13 met inclusion criteria and were included in the meta-analysis. The result of the meta analysis shows a reduction in serum or plasma Zn levels in patients with MS with a 95% CI of [-3.66, -0.93] and a p value of .001 for the difference in Zn concentration in MUM. One of six studies measuring cerebrospinal fluid, Zn levels found a significant increase in patients with MS with controls. The studies measuring whole blood and erythrocyte Zn levels found up to several times higher levels of Zn in patients with MS compared with healthy controls with decreasing levels during attacks in relapsing-remitting MS patients. Future studies measuring serum or plasma Zn are encouraged to analyze their data through homogenous MS patient subgroups on especially age, sex, and disease subtype since the difference in serum or plasma Zn in these subgroups have been found to be significantly different. It is hypothesized that local alterations of Zn may be actively involved in the pathogenesis of MS. PMID- 27282384 TI - Zbtb20 modulates the sequential generation of neuronal layers in developing cortex. AB - BACKGROUND: During corticogenesis, genetic programs encoded in progenitor cells at different developmental stages and inherited in postmitotic neurons specify distinct layer and area identities. Transcription factor Zbtb20 has been shown to play a role for hippocampal development but whether it is implicated in mammalian neocortical morphogenesis remains unknown. RESULTS: Here, we report that during embyogenesis transcription factor Zbtb20 has a dynamic spatio-temporal expression pattern in mitotic cortical progenitors through which it modulates the sequential generation of cortical neuronal layer identities. Zbtb20 knock out mice exhibited enhanced populations of early born L6-L4 neuronal subtypes and a dramatic reduction of the late born L3/L2 neurons. This defect was due to a temporal misbalance in the production of earlier versus later born neurons, leading to a progressive diminishing of the progenitor pool for the generation of L3-L2 neurons. Zbtb20 implements these temporal effects in part by binding to promoter of the orphan nuclear receptor CoupTF1/Nr2f1. In addition to its effects exerted in cortical progenitors, the postmitotic expression of Zbtb20 in L3/L2 neurons starting at birth may contribute to their proper differentiation and migration. CONCLUSIONS: Our findings reveal Zbtb20 as a novel temporal regulator for the generation of layer-specific neuronal identities. PMID- 27282385 TI - Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator. AB - Cancer develops and progresses often by inactivating p53. Here, we unveil nerve growth factor receptor (NGFR, p75NTR or CD271) as a novel p53 inactivator. p53 activates NGFR transcription, whereas NGFR inactivates p53 by promoting its MDM2 mediated ubiquitin-dependent proteolysis and by directly binding to its central DNA binding domain and preventing its DNA-binding activity. Inversely, NGFR ablation activates p53, consequently inducing apoptosis, attenuating survival, and reducing clonogenic capability of cancer cells, as well as sensitizing human cancer cells to chemotherapeutic agents that induce p53 and suppressing mouse xenograft tumor growth. NGFR is highly expressed in human glioblastomas, and its gene is often amplified in breast cancers with wild type p53. Altogether, our results demonstrate that cancers hijack NGFR as an oncogenic inhibitor of p53. PMID- 27282386 TI - Place cells on a maze encode routes rather than destinations. AB - Hippocampal place cells fire at different rates when a rodent runs through a given location on its way to different destinations. However, it is unclear whether such firing represents the animal's intended destination or the execution of a specific trajectory. To distinguish between these possibilities, Lister Hooded rats (n = 8) were trained to navigate from a start box to three goal locations via four partially overlapping routes. Two of these led to the same goal location. Of the cells that fired on these two routes, 95.8% showed route dependent firing (firing on only one route), whereas only two cells (4.2%) showed goal-dependent firing (firing similarly on both routes). In addition, route dependent place cells over-represented the less discriminable routes, and place cells in general over-represented the start location. These results indicate that place cell firing on overlapping routes reflects the animal's route, not its goals, and that this firing may aid spatial discrimination. PMID- 27282388 TI - Astrocyte morphology is confined by cortical functional boundaries in mammals ranging from mice to human. AB - Cortical blood flow can be modulated by local activity across a range of species; from barrel-specific blood flow in the rodent somatosensory cortex to the human cortex, where BOLD-fMRI reveals numerous functional borders. However, it appears that the distribution of blood capillaries largely ignores these functional boundaries. Here we report that, by contrast, astrocytes, a major player in blood flow control, show a striking morphological sensitivity to functional borders. Specifically, we show that astrocyte processes are structurally confined by barrel boundaries in the mouse, by the border of primary auditory cortex in the rat and by layers IIIa/b and Cytochrome Oxidase (CO)-blobs boundaries in the human primary visual cortex. Thus, astrocytes which are critical elements in neuro-hemodynamic coupling show a significant anatomical segregation along functional boundaries across different mammalian species. These results may open a new anatomical marker for delineating functional borders across species, including post-mortem human brains. PMID- 27282387 TI - Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation. AB - How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1alpha and ERRgamma increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size. PMID- 27282390 TI - Anatomical organization of presubicular head-direction circuits. AB - Neurons coding for head-direction are crucial for spatial navigation. Here we explored the cellular basis of head-direction coding in the rat dorsal presubiculum (PreS). We found that layer2 is composed of two principal cell populations (calbindin-positive and calbindin-negative neurons) which targeted the contralateral PreS and retrosplenial cortex, respectively. Layer3 pyramidal neurons projected to the medial entorhinal cortex (MEC). By juxtacellularly recording PreS neurons in awake rats during passive-rotation, we found that head direction responses were preferentially contributed by layer3 pyramidal cells, whose long-range axons branched within layer3 of the MEC. In contrast, layer2 neurons displayed distinct spike-shapes, were not modulated by head-direction but rhythmically-entrained by theta-oscillations. Fast-spiking interneurons showed only weak directionality and theta-rhythmicity, but were significantly modulated by angular velocity. Our data thus indicate that PreS neurons differentially contribute to head-direction coding, and point to a cell-type- and layer-specific routing of directional and non-directional information to downstream cortical targets. PMID- 27282389 TI - A lipoprotein/beta-barrel complex monitors lipopolysaccharide integrity transducing information across the outer membrane. AB - Lipoprotein RcsF is the OM component of the Rcs envelope stress response. RcsF exists in complexes with beta-barrel proteins (OMPs) allowing it to adopt a transmembrane orientation with a lipidated N-terminal domain on the cell surface and a periplasmic C-terminal domain. Here we report that mutations that remove BamE or alter a residue in the RcsF trans-lumen domain specifically prevent assembly of the interlocked complexes without inactivating either RcsF or the OMP. Using these mutations we demonstrate that these RcsF/OMP complexes are required for sensing OM outer leaflet stress. Using mutations that alter the positively charged surface-exposed domain, we show that RcsF monitors lateral interactions between lipopolysaccharide (LPS) molecules. When these interactions are disrupted by cationic antimicrobial peptides, or by the loss of negatively charged phosphate groups on the LPS molecule, this information is transduced to the RcsF C-terminal signaling domain located in the periplasm to activate the stress response. PMID- 27282392 TI - Irradiation-induced grain growth and defect evolution in nanocrystalline zirconia with doped grain boundaries. AB - Grain boundaries are effective sinks for radiation-induced defects, ultimately impacting the radiation tolerance of nanocrystalline materials (dense materials with nanosized grains) against net defect accumulation. However, irradiation induced grain growth leads to grain boundary area decrease, shortening potential benefits of nanostructures. A possible approach to mitigate this is the introduction of dopants to target a decrease in grain boundary mobility or a reduction in grain boundary energy to eliminate driving forces for grain growth (using similar strategies as to control thermal growth). Here we tested this concept in nanocrystalline zirconia doped with lanthanum. Although the dopant is observed to segregate to the grain boundaries, causing grain boundary energy decrease and promoting dragging forces for thermally activated boundary movement, irradiation induced grain growth could not be avoided under heavy ion irradiation, suggesting a different growth mechanism as compared to thermal growth. Furthermore, it is apparent that reducing the grain boundary energy reduced the effectiveness of the grain boundary as sinks, and the number of defects in the doped material is higher than in undoped (La-free) YSZ. PMID- 27282391 TI - Architecture and RNA binding of the human negative elongation factor. AB - Transcription regulation in metazoans often involves promoter-proximal pausing of RNA polymerase (Pol) II, which requires the 4-subunit negative elongation factor (NELF). Here we discern the functional architecture of human NELF through X-ray crystallography, protein crosslinking, biochemical assays, and RNA crosslinking in cells. We identify a NELF core subcomplex formed by conserved regions in subunits NELF-A and NELF-C, and resolve its crystal structure. The NELF-AC subcomplex binds single-stranded nucleic acids in vitro, and NELF-C associates with RNA in vivo. A positively charged face of NELF-AC is involved in RNA binding, whereas the opposite face of the NELF-AC subcomplex binds NELF-B. NELF-B is predicted to form a HEAT repeat fold, also binds RNA in vivo, and anchors the subunit NELF-E, which is confirmed to bind RNA in vivo. These results reveal the three-dimensional architecture and three RNA-binding faces of NELF. PMID- 27282394 TI - Place Cell Networks in Pre-weanling Rats Show Associative Memory Properties from the Onset of Exploratory Behavior. AB - Place cells are hippocampal pyramidal cells that are active when an animal visits a restricted area of the environment, and collectively their activity constitutes a neural representation of space. Place cell populations in the adult rat hippocampus display fundamental properties consistent with an associative memory network: the ability to 1) generate new and distinct spatial firing patterns when encountering novel spatial contexts or changes in sensory input ("remapping") and 2) reinstate previously stored firing patterns when encountering a familiar context, including on the basis of an incomplete/degraded set of sensory cues ("pattern completion"). To date, it is unknown when these spatial memory responses emerge during brain development. Here, we show that, from the age of first exploration (postnatal day 16) onwards, place cell populations already exhibit these key features: they generate new representations upon exposure to a novel context and can reactivate familiar representations on the basis of an incomplete set of sensory cues. These results demonstrate that, as early as exploratory behaviors emerge, and despite the absence of an adult-like grid cell network, the developing hippocampus processes incoming sensory information as an associative memory network. PMID- 27282395 TI - A familial ATP13A2 mutation enhances alpha-synuclein aggregation and promotes cell death. AB - Aberrant protein-protein interactions are a common pathological hallmark among neurodegenerative diseases, including Parkinson's disease (PD). Thus far, mutations in more than 20 genes have been associated with PD. These genes encode for proteins involved in distinct intracellular pathways, complicating our understanding of the precise molecular mechanisms underlying the disease. Recent reports suggested that the endolysosomal protein ATP13A2 can determine the fate of alpha-synuclein (alpha-Syn), although no consensus has yet been reached on the mechanisms underlying this effect. Here, we describe, for the first time, the deleterious effect arising from the interaction between the ATP13A2 familial mutant Dup22 with alpha-Syn. We show that this ATP13A2 mutant can enhance alpha Syn oligomerization and aggregation in cell culture. Additionally, we report the accumulation of both proteins in abnormal endoplasmic reticulum membranous structures and the activation of the protein kinase RNA-like endoplasmic reticulum kinase pathway. Ultimately, our data bring new insight into the molecular mechanisms underlying the interplay of these two proteins, opening novel perspectives for therapeutic intervention. PMID- 27282393 TI - Presynaptic Spike Timing-Dependent Long-Term Depression in the Mouse Hippocampus. AB - Spike timing-dependent plasticity (STDP) is a Hebbian learning rule important for synaptic refinement during development and for learning and memory in the adult. Given the importance of the hippocampus in memory, surprisingly little is known about the mechanisms and functions of hippocampal STDP. In the present work, we investigated the requirements for induction of hippocampal spike timing-dependent long-term potentiation (t-LTP) and spike timing-dependent long-term depression (t LTD) and the mechanisms of these 2 forms of plasticity at CA3-CA1 synapses in young (P12-P18) mouse hippocampus. We found that both t-LTP and t-LTD can be induced at hippocampal CA3-CA1 synapses by pairing presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz). Both t-LTP and t-LTD require NMDA-type glutamate receptors for their induction, but the location and properties of these receptors are different: While t-LTP requires postsynaptic ionotropic NMDA receptor function, t-LTD does not, and whereas t-LTP is blocked by antagonists at GluN2A and GluN2B subunit-containing NMDA receptors, t-LTD is blocked by GluN2C or GluN2D subunit-preferring NMDA receptor antagonists. Both t-LTP and t-LTD require postsynaptic Ca(2+) for their induction. Induction of t-LTD also requires metabotropic glutamate receptor activation, phospholipase C activation, postsynaptic IP3 receptor-mediated Ca(2+) release from internal stores, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signaling, possibly via release of the gliotransmitter d-serine. We furthermore found that presynaptic calcineurin is required for t-LTD induction. t-LTD is expressed presynaptically as indicated by fluctuation analysis, paired-pulse ratio, and rate of use-dependent depression of postsynaptic NMDA receptor currents by MK801. The results show that CA3-CA1 synapses display both NMDA receptor-dependent t-LTP and t-LTD during development and identify a presynaptic form of hippocampal t-LTD similar to that previously described at neocortical synapses during development. PMID- 27282396 TI - Modern advances in heterocyclic chemistry in drug discovery. AB - New advances in synthetic methodologies that allow rapid access to a wide variety of functionalized heterocyclic compounds are of critical importance to the medicinal chemist as it provides the ability to expand the available drug-like chemical space and drive more efficient delivery of drug discovery programs. Furthermore, the development of robust synthetic routes that can readily generate bulk quantities of a desired compound help to accelerate the drug development process. While established synthetic methodologies are commonly utilized during the course of a drug discovery program, the development of innovative heterocyclic syntheses that allow for different bond forming strategies are having a significant impact in the pharmaceutical industry. This review will focus on recent applications of new methodologies in C-H activation, photoredox chemistry, borrowing hydrogen catalysis, multicomponent reactions, regio- and stereoselective syntheses, as well as other new, innovative general syntheses for the formation and functionalization of heterocycles that have helped drive project delivery. Additionally, the importance and value of collaborations between industry and academia in shaping the development of innovative synthetic approaches to functionalized heterocycles that are of greatest interest to the pharmaceutical industry will be highlighted. PMID- 27282397 TI - Histopathologic review of pineal parenchymal tumors identifies novel morphologic subtypes and prognostic factors for outcome. AB - BACKGROUND: Pineal parenchymal tumors (PPTs) are rare neoplasms of the central nervous system, and data concerning clinical outcomes are limited. The purpose of this study was to define the clinical behavior of PPT according to current histopathologic criteria and identify prognostic factors to guide therapeutic decisions. METHODS: Seventy-five patients treated for PPT at a single institution between 1992 and 2015 were retrospectively identified. Forty-five resection specimens were available and re-reviewed. Freedom from progression (FFP) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using log-rank tests. RESULTS: Median follow-up was 4.1 years. All patients initially underwent surgery; 78% of patients with PPT of intermediate differentiation (PPTID) and all patients with pineoblastoma received adjuvant therapy. Pathologic re-review refined classification in 27% of cases, with the majority of these being adult patients with pineal tumors originally classified as pineoblastomas that more accurately resembled PPTID based on the 2007 WHO classification. CLASSIFICATION: Our histologic review also identified that PPTIDs can be classified into small-cell and large-cell morphologic subtypes, which have distinct clinical outcomes. Tumor grade, extent of resection, and neuraxis spread were prognostic for FFP. PPTID subtype, extent of resection, and neuraxis spread were prognostic for OS. Genetic analysis of a pineoblastoma case identified somatic mutations of DICER1, ARID1A, and KDM5C genes. CONCLUSIONS: PPTIDs can be classified into 1 of 2 novel morphologic subtypes that are associated with distinct clinical outcomes. Tumor grade, neuraxis spread, and extent of resection also influence outcome for patients with PPT. PMID- 27282400 TI - Gastroduodenal Involvement in Asymptomatic Crohn's Disease Patients in Two Areas of Emerging Disease: Asia and Eastern Europe. AB - BACKGROUND: The incidence of Crohn's disease [CD] is increasing in Asia and Eastern Europe. Limited studies have reported on the frequency of upper gastrointestinal [GI] involvement in patients with CD in non-Western countries. This prospective study compared the rate of macroscopic and microscopic upper GI manifestations and Helicobacter pylori positivity in asymptomatic CD patients in Asia and Eastern Europe. METHODS: Consecutive asymptomatic CD patients were prospectively recruited for upper GI endoscopy between 2013 and 2015 in Hong Kong and in Hungary. Endoscopy and biopsy findings were recorded and histology was performed to assess for H. pylori and microscopic signs characteristic for CD, using standardized diagnostic criteria. RESULTS: One hundred and eighty CD patients [100 Hong Kong; 80 Hungary; 70.6% male; mean age, 38.5 years] and 189 controls [100 Hong Kong; 89 Hungary; 57.7% male; mean age 41 years] were included. Gastroduodenal involvement of CD was significantly higher in Hungary than in Hong Kong [16.5% vs 2.0%, p <= 0.001]. H. pylori positivity was significantly higher in Hungarian than Chinese CD patients [13.9% vs 4.0%, p <= 0.001]. Granulomas were detected in 1% in Hong Kong and 7.6% in Hungary [p <= 0.001]. Chinese CD subjects had a significantly lower H. pylori positivity compared with controls [6% vs. 15%; p <= 0.001]. CONCLUSIONS: Upper GI CD was significantly higher in Eastern Europe than in Asia. The detection of granuloma in Hungary was similar to the literature data, whereas focal gastritis was lower than expected in both cohorts. PMID- 27282398 TI - Pediatric high-grade glioma: biologically and clinically in need of new thinking. AB - High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management. PMID- 27282401 TI - Disability in Restorative Proctocolectomy Recipients Measured using the Inflammatory Bowel Disease Disability Index. AB - BACKGROUND AND AIMS: The inflammatory bowel disease [IBD] disability index [IBD DI], which measures IBD-associated disability, has been validated on IBD patients but not those who have had restorative proctocolectomy with ileal pouch-anal anastomosis [RP with IPAA]. This study aimed to utilize the IBD-DI in RP with IPAA recipients and compare ulcerative colitis [UC]-indicated RP with IPAA patients to medically treated UC patients. METHODS: This study was population based. Demographic, indication, complication and direct cost data were collected via medical records while disability, quality of life [QoL] and indirect costs were measured using questionnaires and structured interviews. De-identified raw data about medically treated UC patients were provided by a previous study for comparison. RESULTS: In total there were 136 RP with IPAA patients [mean 11.5 years of follow up]. Eighty-four completed the IBD-DI and 80 completed the IBD questionnaire [IBDQ]. The IBDQ and IBD-DI were highly correlated [r = 0.84, p < 0.01]. Worse QoL and disability were found in those who had their position affected at work [both p < 0.01] and those who had more than 100 days off work in the last year [p < 0.01 for QoL and p = 0.012 for disability]. Lower QoL and disability scores were associated with higher indirect and total costs [p < 0.01]. UC patients treated with RP with IPAA had less disability than medically treated UC patients [p = 0.04]. CONCLUSIONS: Disability in RP with IPAA recipients can be measured using the IBD-DI. Perioperative complications and high costs of care are associated with higher levels of disability. Disability of RP with IPAA recipients was lower than that of medically managed UC patients. PMID- 27282399 TI - Stem cell-based therapies for tumors in the brain: are we there yet? AB - Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation. PMID- 27282403 TI - Detection of Streptococcus pneumoniae and Moraxella catarrhalis in patients with paranasal chronic sinusitis by polymerase chain reaction method. AB - BACKGROUND: Sinusitis is a complex involvement of the upper respiratory system by bacteria, viruses, fungi, or other allergens. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the dominant bacterial microorganisms involved in acute sinusitis, whereas in chronic sinusitis, Staphylococcus aureus and some anaerobic bacteria are the prevailing pathogens. Appropriate antibiotic treatment requires sinusitis bacteriology assessment. The aim of this study was to isolate bacteria in clinical samples from patients with chronic sinusitis. METHODS: A total of 55 samples were collected from patients with chronic sinusitis undergoing surgery at Imam Khomeini Hospital in Ahvaz, Iran. Samples were cultured in conventional medium, and for each culture, Gram staining, catalase, coagulase, oxidase, and DNAse tests were performed and isolates were stored for polymerase chain reaction analysis. RESULTS: Twenty three isolates were obtained from five patients, including S. aureus (23.6%), Rhizomucor (1.8%), and Escherichia (1.8%) by the culture method and M. catarrhalis (3.6%) and S. Pneumoniae (7.2%) by the polymerase chain reaction method. Compared with acute sinusitis, the microbiology of chronic sinusitis remains controversial. Results are affected by many factors, including diversity of molecular and culture methods, sterilization of sampling area, sample transfer to laboratory, use of antibiotics prior to surgery, and nasal polyps. CONCLUSION: In Iran, the causative agents of chronic sinusitis are similar to those in other countries. Compared with other bacteria, S. aureus was observed more often in asthmatic patients with sinusitis. PMID- 27282404 TI - Live-cell single-molecule imaging of the cytokine receptor MPL for analysis of dynamic dimerization. PMID- 27282402 TI - Predicting Outcomes to Optimize Disease Management in Inflammatory Bowel Diseases. AB - BACKGROUND AND AIMS: Efforts to slow or prevent the progressive course of inflammatory bowel diseases [IBD] include early and intensive monitoring and treatment of patients at higher risk for complications. It is therefore essential to identify high-risk patients - both at diagnosis and throughout disease course. METHODS: As a part of an IBD Ahead initiative, we conducted a comprehensive literature review to identify predictors of long-term IBD prognosis and generate draft expert summary statements. Statements were refined at national meetings of IBD experts in 32 countries and were finalized at an international meeting in November 2014. RESULTS: Patients with Crohn's disease presenting at a young age or with extensive anatomical involvement, deep ulcerations, ileal/ileocolonic involvement, perianal and/or severe rectal disease or penetrating/stenosing behaviour should be regarded as high risk for complications. Patients with ulcerative colitis presenting at young age, with extensive colitis and frequent flare-ups needing steroids or hospitalization present increased risk for colectomy or future hospitalization. Smoking status, concurrent primary sclerosing cholangitis and concurrent infections may impact the course of disease. Current genetic and serological markers lack accuracy for clinical use. CONCLUSIONS: Simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications at diagnosis and throughout disease course. However, many of these risk factors have been identified retrospectively and lack validation. Appropriately powered prospective studies are required to inform algorithms that can truly predict the risk for disease progression in the individual patient. PMID- 27282406 TI - miR-5003-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization and direct targeting of E-cadherin. AB - One of the initial steps in metastatic dissemination is the epithelial mesenchymal transition (EMT). Along this line, microRNAs (miRNAs) have been shown to function as important regulators of tumor progression at various stages. Therefore, we performed a functional screening for EMT-regulating miRNAs and identified several candidate miRNAs. Among these, we demonstrated that miR-5003 3p induces cellular features characteristic of EMT. miR-5003-3p induced upregulation of Snail, a key EMT-promoting transcription factor and transcriptional repressor of E-cadherin, through protein stabilization. MDM2 was identified as a direct target of miR-5003-3p, the downregulation of which induced Snail stabilization. E-cadherin was also demonstrated to be a direct target of miR-5003-3p, reinforcing the EMT-promoting function of miR-5003-3p. In situ hybridization and immunohistochemical analyses using tissue microarrays revealed that miR-5003-3p expression was higher in paired metastatic breast carcinoma tissues than in primary ductal carcinoma tissues, and was inversely correlated with the expression of MDM2 and E-cadherin. Furthermore, miR-5003-3p enhanced the formation of metastatic nodules in the lungs of mice in a tail vein injection experiment. Collectively, our results suggest that miR-5003-3p functions as a metastasis activator by promoting EMT through dual regulation of Snail stability and E-cadherin, and may therefore be a potential therapeutic target in metastatic cancers. PMID- 27282405 TI - Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis: a novel therapeutic target for fatty liver disease. AB - Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders. The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors. In this study, we investigated the role of a signaling adaptor protein, GRB2-associated-binding protein 2 (Gab2), in fatty liver using an animal disease model. Gab2 expression in hepatocytes responded to various disease factor stimulations, and Gab2 knockout mice exhibited resistance to fat-induced obesity, fat- or alcohol-stimulated hepatic steatosis, as well as methionine and choline deficiency-induced steatohepatitis. Concordantly, the forced expression or knockdown of Gab2 enhanced or diminished oleic acid (OA)- or ethanol-induced lipid production in hepatocytes in vitro, respectively. During lipid accumulation in hepatocytes, both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT, ERK, and Stat3. Therefore, Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver. Our research provides a novel potential target for the prevention and intervention of fatty liver disease. PMID- 27282407 TI - Sonochemical production of nanoparticle metal oxides for potential use in dentistry. AB - Two types of ultrasonic instruments used in dentistry have been compared with a sonochemical horn for the production of copper oxide and zinc oxide nanoparticles. The nanoparticles can be produced from benign reagents using dental instruments as the source of sonochemical enhancement. The process has been operated in resin models of teeth in a preliminary exploration of the potential of the method for enhancing procedures such as root canal surgery. The technique is potentially useful but further work is needed for a full assessment of using in-situ generated nanoparticles as an aid to disinfection during some types of dental surgery. PMID- 27282409 TI - Lemnitoxin, the major component of Micrurus lemniscatus coral snake venom, is a myotoxic and pro-inflammatory phospholipase A2. AB - The venom of Micrurus lemniscatus, a coral snake of wide geographical distribution in South America, was fractionated by reverse-phase HPLC and the fractions screened for phospholipase A2 (PLA2) activity. The major component of the venom, a PLA2, here referred to as 'Lemnitoxin', was isolated and characterized biochemically and toxicologically. It induces myotoxicity upon intramuscular or intravenous injection into mice. The amino acid residues Arg15, Ala100, Asn108, and a hydrophobic residue at position 109, which are characteristic of myotoxic class I phospholipases A2, are present in Lemnitoxin. This PLA2 is antigenically related to M. nigrocinctus nigroxin, Notechis scutatus notexin, Pseudechis australis mulgotoxin, and Pseudonaja textilis textilotoxin, as demonstrated with monoclonal and polyclonal antibodies. Lemnitoxin is highly selective in its targeting of cells, being cytotoxic for differentiated myotubes in vitro and muscle fibers in vivo, but not for undifferentiated myoblasts or endothelial cells. Lemnitoxin is not lethal after intravenous injection at doses up to 2MUg/g in mice, evidencing its lack of significant neurotoxicity. Lemnitoxin displays anticoagulant effect on human plasma and proinflammatory activity also, as it induces paw edema and mast cell degranulation. Thus, the results of this work demonstrate that Lemnitoxin is a potent myotoxic and proinflammatory class I PLA2. PMID- 27282408 TI - Multisensory Processes: A Balancing Act across the Lifespan. AB - Multisensory processes are fundamental in scaffolding perception, cognition, learning, and behavior. How and when stimuli from different sensory modalities are integrated rather than treated as separate entities is poorly understood. We review how the relative reliance on stimulus characteristics versus learned associations dynamically shapes multisensory processes. We illustrate the dynamism in multisensory function across two timescales: one long term that operates across the lifespan and one short term that operates during the learning of new multisensory relations. In addition, we highlight the importance of task contingencies. We conclude that these highly dynamic multisensory processes, based on the relative weighting of stimulus characteristics and learned associations, provide both stability and flexibility to brain functions over a wide range of temporal scales. PMID- 27282410 TI - Evidence for a chemical clock in oscillatory formation of UiO-66. AB - Chemical clocks are often used as exciting classroom experiments, where an induction time is followed by rapidly changing colours that expose oscillating concentration patterns. This type of reaction belongs to a class of nonlinear chemical kinetics also linked to chaos, wave propagation and Turing patterns. Despite its vastness in occurrence and applicability, the clock reaction is only well understood for liquid-state processes. Here we report a chemical clock reaction, in which a solidifying entity, metal-organic framework UiO-66, displays oscillations in crystal dimension and number, as shown by X-ray scattering. In rationalizing this result, we introduce a computational approach, the metal organic molecular orbital methodology, to pinpoint interaction between the tectonic building blocks that construct the metal-organic framework material. In this way, we show that hydrochloric acid plays the role of autocatalyst, bridging separate processes of condensation and crystallization. PMID- 27282411 TI - Parvularcula flava sp. nov., an alphaproteobacterium isolated from surface seawater of the South China Sea. AB - An aerobic, coccoid to short rod, yellow-pigmented, non-sporulating and Gram staining-negative bacterium, designated NH6-79T, was isolated from surface seawater of the South China Sea. The isolate was motile with a polar flagellum. Growth was observed at 4-42 degrees C (optimum 37 degrees C), at pH 6.0-8.5 (optimum pH 7.0), and with 0.5-11 % (w/v) NaCl (optimum 4.5 %) and 1.5-17 % (w/v) sea salt (optimum 3.5-5 %). Strain NH6-79T could decompose peptone to produce H2S, but could not hydrolyse skimmed milk. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NH6-79T had the closest affinity to the genus Parvularcula, sharing the highest 16S rRNA gene sequence similarity with 'Parvularcula oceanus' JLT2013 (94.1 %), Parvularcula lutaonensis CC-MMS-1T (93.4 %), Parvularcula dongshanensis SH25T (92.9 %) and Parvularcula bermudensis HTCC2503T (92.7 %), and lower sequence similarities (<90 %) with all other genera. The dominant fatty acids were C18 : 1omega7c and C16 : 0. The polar lipid profile was mainly composed of three unidentified glycolipids. The predominant isoprenoid quinone was ubiquinone-10. The DNA G+C content was 60.7 mol%. Based on the polyphasic taxonomic characterization, strain NH6-79T is considered to represent a novel species of the genus Parvularcula, for which the name Parvularcula flava sp. nov. is proposed. The type strain is NH6-79T (=CGMCC 1.14984T=JCM 30557T=MCCC 1K00277T). PMID- 27282412 TI - A cost of living longer: Projections of the effects of prospective mortality improvement on economic support ratios for 14 advanced economies. AB - The economic implications of increasing life expectancy are important concerns for governments in developed countries. The aims of this study were as follows: (i) to forecast mortality for 14 developed countries from 2010 to 2050, using the Poisson Common Factor Model; (ii) to project the effects of the forecast mortality patterns on support ratios; and (iii) to calculate labour force participation increases which could offset these effects. The forecast gains in life expectancy correlate negatively with current fertility. Pre-2050 support ratios are projected to fall most in Japan and east-central and southern Europe, and least in Sweden and Australia. A post-2050 recovery is projected for most east-central and southern European countries. The increases in labour force participation needed to counterbalance the effects of mortality improvement are greatest for Japan, Poland, and the Czech Republic, and least for the USA, Canada, Netherlands, and Sweden. The policy implications are discussed. PMID- 27282413 TI - Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles. AB - Alzheimer's disease (AD) pathogenesis is considered to be the metabolic imbalance between anabolism and clearance of amyloid-beta (Abeta), and the strategy of breaking the equilibrium between soluble and insoluble forms of Abeta is likely to help prevent the progression of AD. Neprilysin (NEP) plays a major role in the clearance of Abeta in the brain, and its supplementation using viral vectors has shown to decrease Abeta deposition and prevent pathogenic changes in the brain. In this study, we developed a new therapeutic strategy by mRNA-based gene introduction. mRNA has the advantages of negligible risk of random integration into genome and not needing to be transcribed precludes the need for nuclear entry. This allows efficient protein expression in slowly-dividing or non dividing cells, such as neural cells. We constructed mRNA encoding the mouse NEP protein and evaluated its ability degrade Abeta. In vitro transfection of NEP mRNA to primary neurons exhibited Amyloid Precursor Protein (APP) degradation activity superior to that of NEP encoding plasmid DNA. We then evaluated the in vivo activity of NEP mRNA by intracerebroventricular (i.c.v.) infusion using a cationic polymer-based PEGylated nanocarrier to form polyplex nanomicelles, which have been shown to have a high potential to deliver mRNA to various target tissues and organs. Nanomicelles carrying a GFP-NEP fusion mRNA produced efficient protein expression in a diffuse manner surrounding the ventricular space. An ELISA evaluation revealed that the mRNA infusion significantly augmented NEP level and effectively reduced the concentration of Abeta that had been supplemented in the mouse brain. To the best of our knowledge, this is the first study to demonstrate the therapeutic potential of introducing exogenous mRNA for the treatment of brain diseases, opening the new era of mRNA-based therapeutics. PMID- 27282414 TI - Bladder tumor-targeted delivery of pro-apoptotic peptide for cancer therapy. AB - The overall prognosis of conventional chemotherapy for the treatment of bladder cancer is poor and reduction of its systemic side effects remains an unsolved issue. Targeted therapy for bladder cancer could improve therapeutic efficacy and reduce side effects. This study investigated a hybrid peptide (named Bld-1-KLA) composed of the CSNRDARRC peptide (Bld-1), which binds to bladder tumor cells, and the d-KLAKLAKKLAKLAK (KLA) peptide, which disrupts mitochondrial membrane and induces apoptotic cell death, as a bladder cancer-targeted therapeutic agent. Bld 1-KLA selectively bound to HT1376 bladder tumor cells and efficiently internalized into the cells but not to other types of tumor and normal cell lines. Bld-1-KLA exerted cytotoxic effects selectively to HT1376 cells (LC50=41.5MUM), but not to other types of cells. Pretreatment of cells with Bld-1 inhibited the binding and cytotoxicity by Bld-1-KLA in HT1376 cells. It induced apoptosis of bladder tumor cells, while Bld-1 or KLA alone showed much lesser effect on apoptosis, and was co-localized in mitochondria. Bld-1-KLA was stable up to 24h in serum. In vivo fluorescence imaging showed that homing of Bld-1-KLA in the tumor in HT1376 tumor-bearing nude mice was greater than that of the control peptide-KLA after intravenous injection. Treatment of tumor-bearing mice with Bld-1-KLA, compared to the control peptide-KLA, induced apoptosis of tumor cells and inhibited tumor growth more efficiently. No significant side effects on body weight and the liver and myeloid function were observed in mice treated with Bld-1-KLA. These results suggest that Bld-1-KLA is a promising therapeutic agent for targeted therapy of bladder cancer. PMID- 27282415 TI - Doxorubicin-induced co-assembling nanomedicines with temperature-sensitive acidic polymer and their in-situ-forming hydrogels for intratumoral administration. AB - Doxorubicin (DOX)-induced co-assembling nanomedicines (D-PNAx) with temperature sensitive PNAx triblock polymers have been developed for regional chemotherapy against liver cancer via intratumoral administration in the present work. Owing to the formation of insoluble DOX carboxylate, D-PNAx nanomedicines showed high drug-loading and entrapment efficacy via a simple mixing of doxorubicin hydrochloride and PNAx polymers. The sustained releasing profile of D-PNA100 nanomedicines indicated that only 9.4% of DOX was released within 1day, and 60% was released during 10days. Based on DOX-induced co-assembling behavior and their temperature sensitive in-situ-forming hydrogels, D-PNA100 nanomedicines showed excellent antitumor activity against H22 tumor using intratumoral administration. In contrast to that by free DOX solution (1.13+/-0.04 times at 9days) and blank PNA100 (2.11+/-0.34 times), the tumor volume treated by D-PNA100 had been falling to only 0.77+/-0.13 times of original tumor volume throughout the experimental period. In vivo biodistribution of DOX indicated that D-PNA100 nanomedicines exhibited much stronger DOX retention in tumor tissues than free DOX solution via intratumoral injection. D-PNA100 nanomedicines were hopeful to be developed as new temperature sensitive in-situ-forming hydrogels via i.t. injection for regional chemotherapy. PMID- 27282416 TI - Single cell analysis/data handling: general discussion. PMID- 27282417 TI - Cognitive impairment improves the predictive validity of physical frailty for mortality in patients with advanced heart failure referred for heart transplantation. AB - BACKGROUND: The aim of this study was to identify whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty provides better outcome prediction in patients with advanced heart failure referred for heart transplantation (HT). METHODS: Beginning in March 2013, all patients with advanced heart failure referred to our Transplant Unit have undergone a physical frailty assessment using the Fried frailty phenotype. Cognition was assessed with the Montreal Cognitive Assessment and depression with the Depression in Medical Illness questionnaire. We assessed the value of 4 composite frailty measures: physical frailty (PF >= 3 of 5 = frailty), "cognitive frailty" (CogF >= 3 of 6 = frail), "depressive frailty" (DepF >= 3 of 6 = frail), and "cognitive-depressive frailty" (ComF >= 3 of 7 = frail) in predicting outcomes. RESULTS: Frailty was assessed in 156 patients (109 men, 47 women), aged 53 +/- 13 years, and with a left ventricular ejection fraction of 27% +/- 14%. Inclusion of cognitive impairment or depression in the definition of frailty increased the proportion classified as frail from 33% using PF to 42% using ComF. During follow-up, 28 patients died before ventricular assist device implantation or HT. Frailty was associated with significantly lower ventricular assist device- and HT-free survival, with CogF best capturing early mortality: 12-month survival for non-frail and frail cohorts was 81% +/- 5% vs 58% +/- 10% (p < 0.02) using PF and 85% +/- 5% vs 56% +/- 9% (p < 0.002) using CogF. Combining the Depression in Medical Illness score with PF or CogF did not strengthen the relationship between frailty and mortality. CONCLUSIONS: The addition of cognitive impairment to the assessment of PF strengthened its capacity to identify advanced heart failure patients referred for HT who are at high risk of early death. PMID- 27282418 TI - Ambrisentan use for pulmonary arterial hypertension in a post-authorization drug registry: The VOLibris Tracking Study. AB - BACKGROUND: The VOLibris Tracking (VOLT) Study was an open-label, prospective, observational, multicenter, post-marketing registry program designed to more fully characterize the safety profile of ambrisentan for the treatment of pulmonary arterial hypertension (PAH). The key outcome was the incidence of aminotransferase elevations >3* the upper limit of normal (ULN). METHODS: In total, 999 patients from 115 centers in 15 countries, who were prescribed ambrisentan for the treatment of PAH (Functional Class II and III) between 30 June 2008 and 13 May 2011, were enrolled. Of these, 238 had PAH associated with connective tissue disease (PAH-CTD) and 220 had no prior PAH-specific therapy. Routine clinical monitoring data were collected by physicians. RESULTS: The incidence of both alanine and aspartate aminotransferase events (>3* ULN) was 0.02 per patient-year (95% confidence interval 0.015 to 0.027). Similar results were reported for the PAH-CTD and PAH-specific-therapy-naive subgroups. Overall, 514 (52%) patients reported treatment-emergent adverse events of special interest, most commonly edema/fluid retention (249, or 25%) and anemia (143, or 14%). CONCLUSIONS: Data from the VOLT study indicate no new ambrisentan-related safety signals. Ambrisentan was not associated with increases in liver function test abnormalities above the assumed background incidence of 1.5% per year, and the observed safety profile of ambrisentan was consistent with previously published data. PMID- 27282419 TI - Deletion 2q37 syndrome: Cognitive-behavioral trajectories and autistic features related to breakpoint and deletion size. AB - Subtelomeric deletions have been reported in ~2.5% of individuals with developmental disabilities. Subtelomeric deletion 2q37 has been detected in many individuals diagnosed with intellectual disabilities (ID) and autism spectrum disorders (ASD). Previously, genotype-phenotype correspondences were examined for their relationship to breakpoints 37.1, 37.2, or 37.3. Our purpose was to ascertain whether there were phenotypic differences at these breakpoints, elucidate the cognitive-behavioral phenotype in del2q37, and examine the genotype phenotype association in the deletion with respect to cognitive-behavioral profiles and ASD. We administered a comprehensive cognitive-behavioral battery to nine children diagnosed with del 2q37, ages 3.9-17.75 years. ID for five tested with the Stanford-Binet (4th Edition) (SBFE) ranged from severe to mild [IQ Range: 36-59]. Adaptive behavior scores from the Vineland Adaptive Behavior Scale (VABS) were much below adequate levels (DQ Range: floor value ["19"] to 55). Autism scores from the Child Autism Rating Scale (CARS) ranged from 22 [non autistic] to 56 [extremely autistic]; 5/8 [63%] children received scores on the autism spectrum. Participants with the largest deletions, 10.1 and 9.5 Mb, attained the highest IQ and DQ scores while those with the smallest deletions, 7.9 and 6.6 Mb, made the lowest IQ and DQ scores. No association between deletion breakpoint and phenotype were found. Assessment of the various deleted regions suggested histone deacetylase 4 gene (HDAC4) was a likely candidate gene for ASD in our sample. However, two earlier reports found no association between HDAC4 haploinsufficiency and ASD. (c) 2016 Wiley Periodicals, Inc. PMID- 27282420 TI - Magma transport in sheet intrusions of the Alno carbonatite complex, central Sweden. AB - Magma transport through the Earth's crust occurs dominantly via sheet intrusions, such as dykes and cone-sheets, and is fundamental to crustal evolution, volcanic eruptions and geochemical element cycling. However, reliable methods to reconstruct flow direction in solidified sheet intrusions have proved elusive. Anisotropy of magnetic susceptibility (AMS) in magmatic sheets is often interpreted as primary magma flow, but magnetic fabrics can be modified by post emplacement processes, making interpretation of AMS data ambiguous. Here we present AMS data from cone-sheets in the Alno carbonatite complex, central Sweden. We discuss six scenarios of syn- and post-emplacement processes that can modify AMS fabrics and offer a conceptual framework for systematic interpretation of magma movements in sheet intrusions. The AMS fabrics in the Alno cone-sheets are dominantly oblate with magnetic foliations parallel to sheet orientations. These fabrics may result from primary lateral flow or from sheet closure at the terminal stage of magma transport. As the cone-sheets are discontinuous along their strike direction, sheet closure is the most probable process to explain the observed AMS fabrics. We argue that these fabrics may be common to cone-sheets and an integrated geology, petrology and AMS approach can be used to distinguish them from primary flow fabrics. PMID- 27282421 TI - Sensitivity to hierarchical relations among affordances in the assembly of asymmetric tools. AB - Research on affordances typically has focused on the identification and perception of a single affordance. However, in daily life, multiple affordances are available. We investigated potential hierarchical relations among affordances of tools in two experiments. In Experiment 1, participants assembled a tool consisting of an L-shaped object and attached masses so as to perform a particular behavior on a target object-tipping over or sliding it-located at a particular distance from the participant. In Experiment 2, participants performed the same task with additional precision constraints on the tool use task. In both experiments, participants selected longer objects when target objects were farther away and added more mass to tools to be used for tipping than for sliding. The results were compatible with the hypothesis that participants were simultaneously sensitive to affordances for tool assembly (as revealed in their actualization of affordances in tool assembly) and, prospectively, to affordances for tool use (as revealed in relations between assembled tools and the nature of tasks for which they were assembled). PMID- 27282422 TI - Quadrivalent vaccine-targeted human papillomavirus genotypes in heterosexual men after the Australian female human papillomavirus vaccination programme: a retrospective observational study. AB - BACKGROUND: Australia introduced a national quadrivalent human papillomavirus (4vHPV) vaccination programme for girls and young women in April, 2007. The HPV genotypes targeted by the female vaccine could also affect the protection afforded to heterosexual men. We examined the prevalence of 4vHPV targeted vaccine genotypes and the nine-valent HPV (9vHPV)-targeted vaccines genotypes among sexually active, predominantly unvaccinated heterosexual men from 2004 to 2015. METHODS: We did a retrospective, observational study of urine and urethral swab specimens from heterosexual men aged 25 years or younger attending the Melbourne Sexual Health Centre between July 1, 2004, and June 30, 2015, who tested positive for Chlamydia trachomatis. We extracted HPV DNA and used the PapType HPV assay to detect 14 high-risk HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and two low-risk genotypes (6 and 11). We calculated the prevalence of any HPV genotype, genotypes 6 or 11, genotypes 16 or 18, genotypes in the 4vHPV group (6, 11, 16, or 18), five additional genotypes in the 9vHPV group (31, 33, 45, 52, or 58), and non-vaccine-targeted genotypes (31, 33, 35, 39, 45, 51, 56, 58, 59, 66, or 68). FINDINGS: We obtained data between July 1, 2004, and June 30, 2015, and did the data analysis in December, 2015. Of 1764 specimens obtained, we included 1466 in our final analysis (the others were excluded because they had indeterminate results or were duplicates). The prevalence of any HPV genotype and genotypes 31, 33, 45, 52, and 58 did not change from 2004-05 to 2014-15, but we noted reductions in genotypes 6 and 11 (from 12% [95% CI 6-21%], to 3% [1-7%], ptrend=0.008), 16 and 18 (from 13% [95% CI 7-22%] to 3% [1-6%], ptrend<0.0001), and 4vHPV-targeted genotypes (from 22% [95% CI 14-33%] to 6% [3-10%], ptrend<0.0001). Prevalence of non-vaccine-targeted genotypes increased from 16% [95% CI 9-26%] to 22% [17-29%], ptrend<0.0001). In Australian-born men, 4vHPV-targeted genotype prevalence decreased from 11 of 55 [20%, 95% CI 10-33%] to two of 74 [3%, 0-11%], ptrend<0.0001); an even greater decline occurred in Australian-born men aged 21 years or younger (from four of 13 [31%, 95% CI 9-61%] to none of 25; ptrend<0.0001). Genotypes 16 and 18 decreased (adjusted prevalence ratio [PR] 0.32, 95% CI 0.14-0.74; p=0.008) but not genotypes 6 and 11 (adjusted PR 0.50, 0.16-1.56; p=0.234) in the postvaccination period among men who had arrived in Australia within 2 years from countries with a bivalent vaccine (2vHPV) programme (England, Scotland, Wales, Cook Islands, Northern Ireland, or the Netherlands), compared with the prevaccination period. No change was noted in 4vHPV genotypes in men born overseas in other countries. INTERPRETATION: The marked reduction in prevalence of 4vHPV genotypes among mainly unvaccinated Australian-born men suggests herd protection has occurred from the female vaccination programme. Additionally, the decline in genotypes 16 and 18, but not genotypes 6 and 11, among overseas-born men predominantly from countries with a 2vHPV vaccine programme suggests that these men received benefits from herd protection for genotypes 16 and 18 from their vaccinated female partners in their own countries. These reductions could translate to reductions in HPV-related malignant conditions in men, even in countries with female-only vaccination programmes. FUNDING: The Australian National Health and Medical Research Council Program. PMID- 27282423 TI - Control of HPV-associated cancers with HPV vaccination. PMID- 27282424 TI - Zika virus: history of a newly emerging arbovirus. AB - Zika virus was originally identified in a sentinel rhesus monkey in the Zika Forest of Uganda in 1947. The virus is a member of the family Flaviviridae, genus Flavivirus, and is transmitted to humans by Aedes species mosquitoes. The first report of Zika virus outside Africa and Asia was in 2007 when the virus was associated with a small outbreak in Yap State, part of the Federated States of Micronesia. Since then, Zika virus infections have been reported around the world, including in southeast Asia; French Polynesia and other islands in the Pacific Ocean; and parts of South, Central, and North America. Symptomatic infection in human beings normally results in a mild and self-limiting febrile disease, although recent reports have suggested a possible association with more serious sequelae such as Guillain-Barre syndrome, and microcephaly in newborn infants of mothers infected with Zika virus during pregnancy. In this Review, we summarise the history of Zika virus from its first detection to its current worldwide distribution. PMID- 27282425 TI - Older-adult marijuana users and ex-users: Comparisons of sociodemographic characteristics and mental and substance use disorders. AB - BACKGROUND: The increasing numbers of older-adult marijuana users call for better understanding of their mental and substance use disorders (MSUDs). METHODS: Data came from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; N=14,715 respondents aged 50 +). Multinomial logistic regression analysis was used to compare never users, past-year users, and ex users on past-year and lifetime MSUDs. Binary logistic regression analysis was used to examine the association of marijuana use patterns in the past year and during the peak use period with lifetime MSUDs. RESULTS: Of the 50+ age group, 3.9% were past-year marijuana users and 21.7% were ex-users. Past-year users did not differ from ex-users with respect to past-year or lifetime mental disorders, but they had higher risks of past-year other drug use (RRR=2.73, 95% CI=1.63 4.55), alcohol use (RRR=2.30, 95% CI=1.78-2.98), and tobacco/nicotine use (RRR=1.87, 95% CI=1.50-2.34) disorders. Among past-year users, the number of joints smoked during the peak use period (OR=1.14, 95% CI=1.04-1.26) and past year use frequency (OR=2.20, 95% CI=1.37-3.52) were significantly associated with greater odds of lifetime marijuana/other drug use disorder. Among ex-users, the number of joints smoked during the peak use period was significantly associated with any mental (OR=1.05, 95% CI=1.01-1.09) and marijuana and/or other drug use (OR=1.13, 95% CI=1.06-1.21) disorder. CONCLUSIONS: Older-adult past-year marijuana users and ex-users had similarly high risks for past-year and lifetime mental disorders, but past-year users had a higher risk for substance use disorders. Health/mental health providers should be concerned about the increasing number of older-adult long-term marijuana users with MSUDs. PMID- 27282426 TI - Avoid falling for a jerk(ette): Effectiveness of the Premarital Interpersonal Choices and Knowledge Program among Emerging Adults. AB - Premarital education may help emerging adults form healthy relationships, but evaluation research is needed, particularly with community samples. We studied emerging adults in the Premarital Interpersonal Choices and Knowledge (PICK) program, using a pre- to post- and a posttest-then-retrospective-pretest design to examine change in perceived relationship skills, partner selection, relational patterns, and relationship behaviors and attitudes. Mixed models analyses showed that scores for the treatment group (n = 682) increased from pre to post on all four outcomes. Changes in scores for the nonequivalent comparison group (n = 462) were nonsignificant. In addition, significant differences between pre- and retrospective prescores demonstrated evidence for response shift bias. The results suggest that the PICK program helps participants increase their knowledge regarding the components of healthy relationship formation. PMID- 27282429 TI - Gold nanoparticles: A critical review of therapeutic applications and toxicological aspects. AB - Gold (Au) compounds have been utilized as effective therapeutic agents for the treatment of some inflammatory diseases such as rheumatoid arthritis. However, Au compound use has become limited due to associated high incidence of side effects. Recent development of nanomaterials for therapeutic use with Au-containing drugs is improving the beneficial actions and reducing toxic properties of these agents. Lower toxicity in conjunction with anti-inflammatory and antiangiogenic effects was reported to occur with gold nanoparticles (AuNP) treatment. However, despite this therapeutic potential, safety of AuNP remains to be determined, since the balance between therapeutic properties and development of adverse effects is not well established. Several variables that drive this benefit-risk balance, including physicochemical characteristics of nanoparticles such as size, shape, surface area, and chemistry, are poorly described in the scientific literature. Moreover, therapeutic and toxicological data were obtained employing nonstandardized or poorly described protocols with different experimental settings (animal species/cell type, route and time of exposure). In contrast, effective and safe application of AuNP may be established only after elucidation of various physicochemical properties of each specific AuNP, and determination of respective kinetics and interaction of compound with target tissue. This critical review conveys the state of the art, the therapeutic use, and adverse effects mediated by AuNP, with primary emphasis on anti-inflammatory and antiangiogenic potential, highlighting the limitations/gaps in the scientific literature concerning important points: (i) selection of experimental designs (in vitro and in vivo models) and (ii) consideration of different physicochemical properties of AuNP that are often disregarded in many scientific publications. In addition, prospects and future needs for research in this area are provided. PMID- 27282427 TI - Targeted Spontaneous Reporting: Assessing Opportunities to Conduct Routine Pharmacovigilance for Antiretroviral Treatment on an International Scale. AB - INTRODUCTION: Targeted spontaneous reporting (TSR) is a pharmacovigilance method that can enhance reporting of adverse drug reactions related to antiretroviral therapy (ART). Minimal data exist on the needs or capacity of facilities to conduct TSR. OBJECTIVES: Using data from the International epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium, the present study had two objectives: (1) to develop a list of facility characteristics that could constitute key assets in the conduct of TSR; (2) to use this list as a starting point to describe the existing capacity of IeDEA-participating facilities to conduct pharmacovigilance through TSR. METHODS: We generated our facility characteristics list using an iterative approach, through a review of relevant World Health Organization (WHO) and Uppsala Monitoring Centre documents focused on pharmacovigilance activities related to HIV and ART and consultation with expert stakeholders. IeDEA facility data were drawn from a 2009/2010 IeDEA site assessment that included reported characteristics of adult and pediatric HIV care programs, including outreach, staffing, laboratory capacity, adverse event monitoring, and non-HIV care. RESULTS: A total of 137 facilities were included: East Africa (43); Asia-Pacific (28); West Africa (21); Southern Africa (19); Central Africa (12); Caribbean, Central, and South America (7); and North America (7). Key facility characteristics were grouped as follows: outcome ascertainment and follow-up; laboratory monitoring; documentation-sources and management of data; and human resources. Facility characteristics ranged by facility and region. The majority of facilities reported that patients were assigned a unique identification number (n = 114; 83.2 %) and most sites recorded adverse drug reactions (n = 101; 73.7 %), while 82 facilities (59.9 %) reported having an electronic database on site. CONCLUSION: We found minimal information is available about facility characteristics that may contribute to pharmacovigilance activities. Our findings, therefore, are a first step that can potentially assist implementers and facility staff to identify opportunities and leverage their existing capacities to incorporate TSR into their routine clinical programs. PMID- 27282428 TI - Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis. AB - INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta. OBJECTIVE: The objective was to report outcomes of pregnancy cases identified through April 2014 from tofacitinib RA/psoriasis RCTs, RA post approval non-interventional studies, and spontaneous adverse-event reporting. METHODS: Pregnancy outcomes were categorized as follows: healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or pending/lost to follow-up. RESULTS: Out of 9815 patients, 1821 female patients of child-bearing age were enrolled in the RA/psoriasis RCTs; 47 women became pregnant, including 33 who received tofacitinib monotherapy, 13 who received combination therapy with methotrexate (RA patients only), and one patient whose therapy was still blinded. No fetal deaths were reported. One congenital pulmonary valve stenosis (monotherapy, n = 1), seven spontaneous abortions (monotherapy, n = 4; combination therapy, n = 3), and eight medical terminations (monotherapy, n = 4; combination therapy, n = 3; blinded therapy, n = 1) were identified. Remaining cases reported healthy newborns (n = 25) or were pending/lost to follow-up (n = 6). Forty-four cases of paternal exposure to tofacitinib were reported (monotherapy, n = 43; combination therapy, n = 1), including five spontaneous abortions (monotherapy, n = 4; combination therapy, n = 1), 23 healthy newborns, and 16 pending/lost to follow-up. CONCLUSIONS: The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored. PMID- 27282430 TI - Remarkable Improvement in the Mechanical Properties and CO2 Uptake of MOFs Brought About by Covalent Linking to Graphene. AB - Metal-organic frameworks (MOFs) are exceptional as gas adsorbents but their mechanical properties are poor. We present a successful strategy to improve the mechanical properties along with gas adsorption characteristics, wherein graphene (Gr) is covalently bonded with M/DOBDC (M=Mg(2+) , Ni(2+) , or Co(2+) , DOBDC=2,5 dioxido-1,4-benzene dicarboxylate) MOFs. The surface area of the graphene-MOF composites increases up to 200-300 m(2) g(-1) whereas the CO2 uptake increases by ca. 3-5 wt % at 0.15 atm and by 6-10 wt % at 1 atm. What is significant is that the composites exhibit improved mechanical properties. In the case of Mg/DOBDC, a three-fold increase in both the elastic modulus and hardness with 5 wt % graphene reinforcement is observed. Improvement in both the mechanical properties and gas adsorption characteristics of porous MOFs on linking them to graphene is a novel observation and suggests a new avenue for the design and synthesis of porous materials. PMID- 27282433 TI - Corrigendum to "Macroporous natural capsules extracted from Phoenix dactylifera L. spore and their application in oral drugs delivery" [Int. J. Pharm. 504 (2016) 39-47]. PMID- 27282431 TI - Implementation of an evidence-based intervention to promote colorectal cancer screening in community organizations: a cluster randomized trial. AB - The implementation of evidence-based strategies to promote colorectal cancer (CRC) screening remains challenging. The aim of this study is to evaluate two strategies to implement an evidence-based intervention to promote CRC screening in Filipino American community organizations. Twenty-two community organizations were randomized to either a basic or enhanced implementation strategy. In both arms, community health advisors recruited participants non-adherent to CRC screening guidelines, conducted educational sessions, distributed print materials and free fecal occult blood test kits, reminded participants to get screened, and mailed letters to participants' providers. In the enhanced arm, leaders of the organizations participated in implementation efforts. While the effectiveness was similar in both arms of the study (screening rate at 6-month follow-up was 53 % in the enhanced arm, 49 % in the basic arm), 223 participants were screened in the enhanced arm versus 122 in the basic arm. The enhanced implementation strategy reached 83 % more participants and achieved a higher public health impact. TRIAL REGISTRATION: NCT01351220 (ClinicalTrials.gov). PMID- 27282432 TI - UWALK: the development of a multi-strategy, community-wide physical activity program. AB - UWALK is a multi-strategy, multi-sector, theory-informed, community-wide approach using e and mHealth to promote physical activity in Alberta, Canada. The aim of UWALK is to promote physical activity, primarily via the accumulation of steps and flights of stairs, through a single over-arching brand. This paper describes the development of the UWALK program. A social ecological model and the social cognitive theory guided the development of key strategies, including the marketing and communication activities, establishing partnerships with key stakeholders, and e and mHealth programs. The program promotes the use of physical activity monitoring devices to self-monitor physical activity. This includes pedometers, electronic devices, and smartphone applications. In addition to entering physical activity data manually, the e and mHealth program provides the function for objective data to be automatically uploaded from select electronic devices (Fitbit(r), Garmin and the smartphone application Moves) The RE-AIM framework is used to guide the evaluation of UWALK. Funding for the program commenced in February 2013. The UWALK brand was introduced on April 12, 2013 with the official launch, including the UWALK website on September 20, 2013. This paper describes the development and evaluation framework of a physical activity promotion program. This program has the potential for population level dissemination and uptake of an ecologically valid physical activity promotion program that is evidence-based and theoretically framed. PMID- 27282434 TI - How to Reach Emotions with Psychosomatic Patients: A Case Report. AB - Alopecia areata (patchy hairloss) often indicates to the dermatologist the existence of psychological disorders, mostly anxiety and depression. Psychosomatic conditions are usually associated with difficulty in expressing emotions, as is the case in alexithymia, and this difficulty is often seen in patients with alopecia areata. This case study aims to show how to help these patients connect with their emotions and how the somatic symptom can become meaningful by using a unifying approach, which challenges the beliefs, the rules and the interactions of both the individual and the family, as well as the emotions expressed or suppressed. In this particular case we used a systemic family therapy tool, "the family blazon" that helped to discover the unconscious myth of unity and the fear of family disaggregation that is involved in psychosomatic families. PMID- 27282435 TI - Quality of life and disease severity in patients with atopic dermatitis. AB - BACKGROUND: Atopic dermatitis (AD) affects quality of life (QoL) negatively in patients and their families. We examined the relationship between disease severity and QoL in patients with AD. METHODS: Consecutive, newly referred outpatients with AD, 4 years of age or older, were assessed from January 2012 onwards by means of the dermatology life quality index (DLQI, range 0-30), the Scoring of AD (SCORAD) disease severity score (range 0-103), filaggrin gene (FLG) mutation status and paraclinical tests related to allergy. RESULTS: A total of 250 patients with a mean age of 26.0 years were identified with complete data on DLQI; 148 (59.2%) females and 102 (40.8%) males. Of these 45.6% had asthma, 46.8% had hay fever, 22.7% had a loss-of-function mutation in FLG, and 61.9% had one or more inhalant allergic sensitizations. The correlation between SCORAD and DLQI was 0.42 (P < 0.001). After multivariate adjustment there was an increasing mean DLQI score with increasing disease severity measured by SCORAD (DLQI in mild = 5.30, moderate = 8.59 and severe = 11.94 AD), P-value for difference between groups <0.001; a higher mean DLQI among females than males (9.73 vs. 8.34), P = 0.028; and among patients reporting facial eczema (9.88 vs. 6.24), P = 0.012. No statistically significant influence on DLQI was found for hand or foot eczema, age, blood eosinophil count, allergic sensitization, asthma, hay fever, FLG mutation status and smoking. FLG null mutation status was not significantly associated with SCORAD. CONCLUSION: AD impacts negatively on the QoL, proportional to the severity of the disease. Furthermore, female sex and facial eczema are associated with low QoL. Positive FLG null mutation status is not associated with QoL or disease severity. PMID- 27282436 TI - Multifocal Lymphangioendotheliomatosis with Thrombocytopenia: Presentation of Two Cases Treated with Sirolimus. AB - Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disease characterized by congenital and progressive vascular lesions of the skin and gastrointestinal tract that may be associated with thrombocytopenia and possibly life-threatening gastrointestinal bleeding. Reports published on the disease and treatment strategies are scarce. We present two cases of MLT treated with sirolimus. PMID- 27282437 TI - Transitions of Care Between Acute and Chronic Heart Failure: Critical Steps in the Design of a Multidisciplinary Care Model for the Prevention of Rehospitalization. AB - Despite advances in the treatment of heart failure, mortality, the number of readmissions, and their associated health care costs are very high. Heart failure care models inspired by the chronic care model, also known as heart failure programs or heart failure units, have shown clinical benefits in high-risk patients. However, while traditional heart failure units have focused on patients detected in the outpatient phase, the increasing pressure from hospital admissions is shifting the focus of interest toward multidisciplinary programs that concentrate on transitions of care, particularly between the acute phase and the postdischarge phase. These new integrated care models for heart failure revolve around interventions at the time of transitions of care. They are multidisciplinary and patient-centered, designed to ensure continuity of care, and have been demonstrated to reduce potentially avoidable hospital admissions. Key components of these models are early intervention during the inpatient phase, discharge planning, early postdischarge review and structured follow-up, advanced transition planning, and the involvement of physicians and nurses specialized in heart failure. It is hoped that such models will be progressively implemented across the country. PMID- 27282438 TI - Contagious risk taking: social information and context influence wild jackdaws' responses to novelty and risk. AB - Although wild animals increasingly encounter human-produced food and objects, it is unknown how they learn to discriminate beneficial from dangerous novelty. Since social learning allows animals to capitalize on the risk-taking of others, and avoid endangering themselves, social learning should be used around novel and unpredictable stimuli. However, it is unclear whether animals use social cues equally around all types of novelty and at all times of year. We assessed whether wild, individually marked jackdaws-a highly neophobic, yet adaptable species-are equally influenced by social cues to consume novel, palatable foods and to approach a startling object. We conducted these tests across two seasons, and found that in both seasons observers were more likely to consume novel foods after seeing a demonstrator do so. In contrast, observers only followed the demonstrator in foraging next to the object during breeding season. Throughout the year more birds were wary of consuming novel foods than wary of approaching the object, potentially leading to jackdaws' greater reliance on social information about food. Jackdaws' dynamic social cue usage demonstrates the importance of context in predicting how social information is used around novelty, and potentially indicates the conditions that facilitate animals' adjustment to anthropogenic disturbance. PMID- 27282441 TI - Would an FFR by Any Technique Perform as Sweet? PMID- 27282440 TI - Follow-Up of Pulmonary Hypertension With Echocardiography. AB - Individual patient response to effective therapies for pulmonary hypertension (PAH) is variable and difficult to quantify. Consequently, management decisions regarding initiation and continuation of therapy are highly dependent on the results of investigations. Registry data show that changes in cardiac index, mean right atrial pressure, and mean pulmonary artery pressure have the greatest influence on survival. It is recognized that pulmonary artery pressure (PASP) responses to PAH-specific drugs are heterogeneous. However, follow-up testing is strongly focused on assessing changes in PASP and functional status (6-min walk). The goals of therapy, which should be highlighted in follow-up imaging, include not only reduction of PASP, decrease in pulmonary vascular resistance, and improvements in right ventricular function, cardiac output, and tricuspid regurgitation. This paper reviews the echocardiographic follow-up of pulmonary hypertension, and especially focuses on right ventricular function-a major determinant of outcome, for which reliable echocardiographic assessment has become more feasible. PMID- 27282439 TI - MR and CT Imaging for the Evaluation of Pulmonary Hypertension. AB - Imaging plays a central role in the diagnosis and management of all forms of pulmonary hypertension (PH). Although Doppler echocardiography is essential for the evaluation of PH, its ability to optimally evaluate the right ventricle and pulmonary vasculature is limited by its 2-dimensional planar capabilities. Magnetic resonance and computed tomography are capable of determining the etiology and pathophysiology of PH, and can be very useful in the management of these patients. Exciting new techniques such as right ventricle tissue characterization with T1 mapping, 4-dimensional flow of the right ventricle and pulmonary arteries, and computed tomography lung perfusion imaging are paving the way for a new era of imaging in PH. These imaging modalities complement echocardiography and invasive hemodynamic testing and may be useful as surrogate endpoints for early phase PH clinical trials. Here we discuss the role of magnetic resonance imaging and computed tomography in the diagnosis and management of PH, including current uses and novel research applications, and we discuss the role of value-based imaging in PH. PMID- 27282442 TI - The internalization of Helicobacter pylori plays a role in the failure of H. pylori eradication. AB - BACKGROUND: Helicobacter pylori (H. pylori) internalization involves invasion of cells by the bacterium. Several studies have shown that H. pylori can invade human gastric epithelial cells, immune cells, and Candida yeast in vivo and in vitro. Whether bacterial invasion plays a role in eradication failure is unclear. AIM: To investigate the relationship between H. pylori invasion of GES-1 cells and H. pylori eradication failure. MATERIALS AND METHODS: Forty-two clinical strains isolated from H. pylori-positive patients with different outcomes after treatment with furazolidone-based therapy were examined (17 failures and 25 successes). The H. pylori strains were shown to be susceptible to amoxicillin and furazolidone, and the patients also exhibited good compliance. Genotyping was performed for cagA and vacA (s and m). The antibiotic susceptibility of the strains to amoxicillin, furazolidone, clarithromycin, metronidazole, and levofloxacin was determined by E-tests. The levels of H. pylori invasion of GES-1 cells were detected by gentamicin colony-forming unit assays. RESULTS: The internalization level in the eradication success group was 5.40+/-5.78 * 10-3 cfu/cell, and the median was 6.194 * 10-3 cfu/cell; the internalization level in the eradication failure group was 8.98+/-5.40 * 10-3 cfu/cell, and the median was 10.28 * 10-3 cfu/cell. The eradication failure group showed a greater invasion level than the eradication success group (P<.05). No significant difference was observed between the susceptible strains and the resistant strains when the internalization levels were compared (P>.05). CONCLUSIONS: The results showed that H. pylori invasion of the gastric epithelia might play a role in eradication failure. PMID- 27282443 TI - [Inflammatory papules and nodi in a 52-year-old woman after a vacation in Zanzibar]. PMID- 27282444 TI - Neuroendocrinology: Exome sequencing aids targeted treatment of inborn errors of metabolism. PMID- 27282445 TI - Reproductive endocrinology: Acquisition of kisspeptin responsiveness is key to reversal of hypogonadotropic hypogonadism. PMID- 27282446 TI - In the news: ECE2016 - like-minds meet in Munich. PMID- 27282447 TI - Adipose tissue: Adipocyte exosomes drive melanoma progression. PMID- 27282448 TI - Metabolism: Acetate promotes obesity via a gut-brain-beta-cell axis. PMID- 27282449 TI - Prognostic value of post-treatment metabolic tumor volume from 11C-methionine PET/CT in recurrent malignant glioma. AB - We investigated the diagnostic and prognostic significance of metabolic parameters from 11C-methionine (MET) positron emission tomography (PET) in patients with malignant glioma. The MET-PET was examined in 42 patients who had been previously treated with adjuvant treatment for malignant glioma. Both ratios of maximal MET uptake of the tumors to those of the contralateral normal gray matter (T/N ratio) and metabolic tumor volume (MTV) were estimated in each lesion. The diagnostic performance for recurrence was investigated in all enrolled patients. A definitive diagnosis was done with pathologic confirmation or clinical follow-up. Among recurrent patients, we evaluated the prognostic value of metabolic parameters (T/N ratio and MTV) as well as clinical factors. Among 42 patients, 35 patients were revealed with recurrence. Both T/N ratios (p = 0.009) and MTV (p = 0.001) exhibited statistical significance to differentiate between recurrence and post-treatment radiation effect. A T/N ratio of 1.43 provided the best sensitivity and specificity for recurrence (91.4 and 100 %, respectively), and a MTV of 6.72 cm3 provided the best sensitivity and specificity (77.1 % and 100 %, respectively). To evaluate the prognostic impact, different cutoffs of MTV were examined in patients with recurrent tumor and a threshold of 60 cm3 was determined as a best cutoff value to separate the patients in two prognostic groups. Univariate analysis revealed improved overall survival (OS) for patients with Karnofsky performance scale (KPS) score >=70 (p < 0.001) or MTV <60 cm3 (p = 0.049). Multivariate analysis showed that patients with KPS score >=70 (p < 0.001; hazard ratio = 0.104; 95 % CI, 0.029-0.371) or MTV < 60 cm3 (p = 0.031; hazard ratio = 0.288; 95 % CI, 0.093-0.895) were significantly associated with a longer OS. However, T/N ratio was not correlated with patients' outcome. Metabolic parameters had the diagnostic value to differentiate recurrence from post-treatment radiation effect. Compared with T/N ratio, MTV was an independent significant prognostic factor with KPS score in patients with recurrent tumor. Our study had a potential to manage these patients according to prognostic information using MET-PET. PMID- 27282450 TI - Profession of neuropsychology in Latin America. AB - The purpose of this study was to analyze characteristics of individuals working in the profession of neuropsychology in Latin America in order to understand their background, professional training, current work situation, assessment and diagnostic procedures used, rehabilitation techniques employed, population targeted, teaching responsibilities, and research activities. A total of 808 professionals working in neuropsychology from 17 countries in Latin America completed an online survey between July 2013 and January 2014. The majority of participants were female and the mean age was 36.76 years (range 21-74 years). The majority of professionals working in neuropsychology in Latin America have a background in psychology, with some additional specialized training and supervised clinical practice. Over half work in private practice, universities, or private clinics and are quite satisfied with their work. Those who identify themselves as clinicians primarily work with individuals with learning problems, ADHD, mental retardation, TBI, dementia, and stroke. The majority respondents cite the top barrier in the use of neuropsychological instruments to be the lack of normative data for their countries. The top perceived barriers to the field include: lack of academic training programs, lack of clinical training opportunities, lack of willingness to collaborate between professionals, and lack of access to neuropsychological instruments. There is a need in Latin America to increase regulation, improve graduate curriculums, enhance existing clinical training, develop professional certification programs, validate existing neuropsychological tests, and create new, culturally-relevant instruments. PMID- 27282451 TI - Predictive Factors for Anastomotic Leakage After Colorectal Surgery: Study Protocol for a Prospective Observational Study (REVEAL Study). AB - BACKGROUND: Anastomotic leakage (AL) remains the most important complication following colorectal surgery, and is associated with high morbidity and mortality rates. Previous research has focused on identifying risk factors and potential biomarkers for AL, but the sensitivity of these tests remains poor. OBJECTIVE: This prospective multicenter observational study aims at combining multiple parameters to establish a diagnostic algorithm for colorectal AL. METHODS: This study aims to include 588 patients undergoing surgery for colorectal carcinoma. Patients will be eligible for inclusion when surgery includes the construction of a colorectal anastomosis. Patient characteristics will be collected upon consented inclusion, and buccal swabs, breath, stool, and blood samples will be obtained prior to surgery. These samples will allow for the collection of information regarding patients' inflammatory status, genetic predisposition, and intestinal microbiota. Additionally, breath and blood samples will be taken postoperatively and patients will be strictly observed during their in-hospital stay, and the period shortly thereafter. RESULTS: This study has been open for inclusion since August 2015. CONCLUSIONS: An estimated 8-10% of patients will develop AL following surgery, and they will be compared to non-leakage patients. The objectives of this study are twofold. The primary aim is to establish and validate a diagnostic algorithm for the pre-operative prediction of the risk of AL development using a combination of inflammatory, immune-related, and genetic parameters. Previously established risk factors and novel parameters will be incorporated into this algorithm, which will aid in the recognition of patients who are at risk for AL. Based on these results, recommendations can be made regarding the construction of an anastomosis or deviating stoma, and possible preventive strategies. Furthermore, we aim to develop a new algorithm for the post-operative diagnosis of AL at an earlier stage, which will positively reflect on short-term survival rates. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02347735; https://clinicaltrials.gov/ct2/show/NCT02347735 (archived by WebCite at http://www.webcitation.org/6hm6rxCsA). PMID- 27282452 TI - Centrifugation as a countermeasure during bed rest and dry immersion: What has been learned? AB - OBJECTIVES: We review the studies that have evaluated intermittent short-radius centrifugation as a potential countermeasure for cardiovascular, musculoskeletal, and sensorimotor deconditioning in simulated weightlessness. METHODS: The findings from 18 experimental protocols that have used bed rest and dry immersion for comparing the protective effects of centrifugation versus standing upright or walking, and the effects of continuous vs. periodic exposure to centrifugation are discussed. RESULTS: Centrifugation for as little as 30 min per day was found to be effective in mitigating orthostatic intolerance and strength in postural muscle after 5 days of bed rest, but it was not effective in mitigating plasma volume loss. CONCLUSION: To determine the optimal prescription for centrifugation as a countermeasure, we recommend further studies using (a) bed rest of longer duration, (b) individualized prescriptions of centrifugation combined with exercise, and PMID- 27282453 TI - The effect of female sex hormone supplementation on tendon in pre and postmenopausal women: A systematic review. AB - OBJECTIVES: Oestrogen deprivation has been shown to have a negative effect on connective tissue and its turnover. A link may exist between supplemental oestrogen, preservation of tendon collagen and less tendon abnormality. The aim was to determine the effects of female sex hormone supplementation (FSHS) on tendon. METHODS: A systematic search of nine key health databases; Medline, CINAHL, EMBASE, SPORTDiscus, AUSPORT and AMI, Cochrane Library, SafetyLit and PEDro was completed (to Feb 24, 2016). The search yielded 6378 records using terms relating to hormone (oestrogen, estrogen, hormone replacement therapy, HRT, estrogen therapy, oestrogen therapy, oral contraceptive pill) and tendon. Quality assessment, data extraction and data synthesis of included papers was undertaken. RESULTS: Low level of evidence for all outcomes; no positive or negative link between FSHS and molecular, mechanical and morphological tendon response outcomes, and the addition of exercise to FSHS, had minimal effects on tendon CSA. CONCLUSIONS: The effect of oestrogen supplementation on tendon is contradictory and inconsistent. This review suggests there is a need for further studies to understand the effects of FSHS on tendon tissue at a mechanical, morphological and molecular level. PMID- 27282455 TI - Differences of bone mineral mass, volumetric bone mineral density, geometrical and structural parameters and derived strength of the tibia between premenopausal and postmenopausal women of different age groups: a peripheral Quantitative Computed Tomography (pQCT) study. AB - Menopause constitutes a significant cause of bone loss, and it is currently debated whether bone mass is preserved or begins to decline substantially before that time in women. We used pQCT of the tibia to estimate differences of bone mineral mass, bone geometry and derived strength between premenopausal and postmenopausal Caucasian women of different age-groups per decade of age (20 79y). For each individual, we assessed total, trabecular and cortical bone mineral content (BMC, mg) and volumetric bone mineral density (BMD, mg/cm3); total and cortical cross-sectional areas (CSA, mm2); periosteal circumference (PERI_C, mm); endosteal circumference (ENDO_C, mm); mean cortical thickness (CRT_THK, mm); and Stress-Strain Index (SSI) . Comparisons were made both between premenopausal (N=84) and postmenopausal (N=231) women as distinct groups, and among women of the different age-groups. Our results indicated that premenopausal women had significantly higher trabecular and cortical BMC and vBMD, with higher cortical CSA, CRT_THK and SSI than postmenopausal women. Moreover, significant differences of trabecular but not cortical BMC, vBMD or SSI were found between women of the younger (<48y) age-groups. PERI_C, ENDO_C displayed lower values in the 20-29y group and higher values in the 70-79y group, denoting significant differences of bone geometry with aging. PMID- 27282454 TI - Achilles tendon material properties are greater in the jump leg of jumping athletes. AB - PURPOSE: The Achilles tendon (AT) must adapt to meet changes in demands. This study explored AT adaptation by comparing properties within the jump and non-jump legs of jumping athletes. Non-jumping control athletes were included to control limb dominance effects. METHODS: AT properties were assessed in the preferred (jump) and non-preferred (lead) jumping legs of male collegiate-level long and/or high jump (jumpers; n=10) and cross-country (controls; n=10) athletes. Cross sectional area (CSA), elongation, and force during isometric contractions were used to estimate the morphological, mechanical and material properties of the ATs bilaterally. RESULTS: Jumpers exposed their ATs to more force and stress than controls (all p<=0.03). AT force and stress were also greater in the jump leg of both jumpers and controls than in the lead leg (all p<0.05). Jumpers had 17.8% greater AT stiffness and 24.4% greater Young's modulus in their jump leg compared to lead leg (all p<0.05). There were no jump versus lead leg differences in AT stiffness or Young's modulus within controls (all p>0.05). CONCLUSION: ATs chronically exposed to elevated mechanical loading were found to exhibit greater mechanical (stiffness) and material (Young's modulus) properties. PMID- 27282456 TI - Severe muscle trauma triggers heightened and prolonged local musculoskeletal inflammation and impairs adjacent tibia fracture healing. AB - OBJECTIVES: Complicated fracture healing is often associated with the severity of surrounding muscle tissue trauma. Since inflammation is a primary determinant of musculoskeletal health and regeneration, it is plausible that delayed healing and non-unions are partly caused by compounding local inflammation in response to concomitant muscle trauma. METHODS AND RESULTS: To investigate this possibility, a Lewis rat open fracture model [tibia osteotomy with adjacent tibialis anterior (TA) muscle volumetric muscle loss (VML) injury] was interrogated. We observed that VML injury impaired tibia healing, as indicated by diminished mechanical strength and decreased mineralized bone within the fracture callus, as well as continued presence of cartilage instead of woven bone 28 days post-injury. The VML injured muscle presented innate and adaptive immune responses that were atypical of canonical muscle injury healing. Additionally, the VML injury resulted in a perturbation of the inflammatory phase of fracture healing, as indicated by elevations of CD3(+) lymphocytes and CD68+ macrophages in the fracture callus at 3 and 14d post-injury, respectively. CONCLUSIONS: These data indicate that heightened and sustained innate and adaptive immune responses to traumatized muscle are associated with impaired fracture healing and may be targeted for the prevention of delayed and non-union following musculoskeletal trauma. PMID- 27282457 TI - Four weeks of high- versus low-load resistance training to failure on the rate of torque development, electromechanical delay, and contractile twitch properties. AB - The purpose of this study was to investigate the effects of 4-weeks of high- versus low-load resistance training to failure on rate of torque development (RTD), electromechanical delay (EMD), and contractile twitch characteristics. Fifteen men (mean+/-SD; age=21.7+/-2.4 yrs) were randomly assigned to either a high- (80% 1RM; n=7) or low-load (30% 1RM; n=8) training group and completed elbow flexion resistance training to failure 3 times per week for 4 weeks. The participants were tested at baseline, 2-, and 4-weeks of training. Peak RTD (pRTDV) and RTD at 0-30 (RTD30V), 0-50 (RTD50V), 0-100 (RTD100V), and 0-200 (RTD200V) ms, integrated EMG amplitude (iEMG) at 0-30, 0-50, and 0-100 ms, and EMD were quantified during maximal voluntary isometric muscle actions. Peak twitch torque, peak RTD, time to peak twitch, 1/2 relaxation time and the peak relaxation rate were quantified during evoked twitches. Four weeks of high-load, but not low-load resistance training, increased RTD200V. There were also increases in iEMG during the first 30 ms of muscle activation for the high- and low-load groups, which may have indirectly indicated increases in early phase motor unit recruitment and/or firing frequency. There were no significant training-induced adaptations in EMD or contractile twitch properties. PMID- 27282458 TI - TRPV1, ASICs and P2X2/3 expressed in bone cells simultaneously regulate bone metabolic markers in ovariectomized mice. AB - OBJECTIVES: Nociceptors are expressed at peripheral terminals of neurons. Recent studies have shown that TRPV1, a nociceptor, is expressed in bone tissue and regulates bone metabolism. We have demonstrated that a TRPV1 antagonist improved pain-like behavior in ovariectomized (OVX) mice. The aim of this study was to determine whether nociceptors, including TRPV1, acid-sensing ion channel (ASIC) and P2X2/3 are expressed in bone cells, and to examine the effects of nociceptor antagonists on bone metabolism. METHODS: The expression of nociceptors in femoral bone tissue and cultured bone marrow cells in OVX and sham-operated mice were examined. The effects of nociceptor antagonists on the up-regulated expression of bone metabolic markers, Runx2, Osterix, osteocalcin and RANKL, were also examined. RESULTS: TRPV1, ASIC 2 and 3, and P2X2 and 3, were expressed in bone tissue and bone marrow cells, and the expression levels of ASIC1 and 2, and P2X2 were significantly increased in OVX mice in comparison with those in sham mice. Treatment with nociceptor antagonists significantly inhibited the expression of bone metabolic markers in OVX mice. CONCLUSION: An array of nociceptors, TRPV1, ASICs and P2X2/3, could simultaneously regulate not only increases in skeletal pain but also bone turnover in OVX mice. PMID- 27282459 TI - Preventive effects of kilohertz frequency electrical stimulation on sepsis induced muscle atrophy. AB - OBJECTIVES: The present study sought to evaluate the effect of electrical stimulation (ES) by using kilohertz frequency on muscle atrophy induced by sepsis. METHODS: Seventeen male ICR mice were randomly divided into 3 groups: control, lipopolysaccharide (LPS)-injected for 4 days, LPS plus ES (LPS+ES). Sepsis was induced by 4 days of an intraperitoneal LPS injection (10 MUg/g body weight/day). LPS+ES animals received the LPS injections and ES twice a day for 4 days. ELISA and western blot analysis determined the plasma levels of inflammatory cytokines and ubiquitinated proteins, while the tibialis anterior muscles were weighed and muscle fiber cross-sectional area (CSA) were measured to assess muscle atrophy, which were analyzed by Student's t-test and ANOVA. RESULTS: LPS induced increased plasma levels of inflammatory cytokines, significant muscle mass loss (LPS: -29.0%, LPS+ES: -23.1%), decreased fiber cross sectional area, and an up-regulation of atrogin-1 and ubiquitinated proteins in the tibialis anterior muscle compared with the control. ES attenuated the sepsis induced loss of muscle mass and decreased fiber CSA, as well as attenuated the atrogin-1 and ubiquitinated protein up-regulation. CONCLUSIONS: Electrical stimulation may prevent sepsis-induced muscle atrophy through ubiquitin proteasome pathway inhibition. PMID- 27282460 TI - Effects of collagen hydrolysate on the tibialis anterior muscle and femur in senescence-accelerated mouse prone 6. AB - OBJECTIVES: Effects of collagen hydrolysate (CHD) on the oxidative capacity of the tibialis anterior muscle and the cortical and trabecular density of the femur were investigated in senescence-accelerated mouse prone 6 (SAMP6). METHODS: Sixteen-week-old male SAMP6 mice were divided into control (CON) and CHD groups. The CON group was given normal water, while the CHD group was given water containing CHD. Fibre cross-sectional areas (CSAs), fibre succinate dehydrogenase (SDH) staining intensity, and SDH activity of the tibialis anterior muscle were determined at 42 and 60 weeks of age. The cortical and trabecular density of the femur and serum osteocalcin levels were also determined. RESULTS: The fibre SDH staining intensity and muscle SDH activity were higher in the CHD group at 60 weeks of age than in the age-matched CON group. The cortical and trabecular density and serum osteocalcin levels were greater in the CHD group at 60 weeks of age than in the age-matched CON group. CONCLUSION: CHD inhibited th age-induced decrease in muscle oxidative capacity and bone density of SAMP6 mice. There is a possibility that CHD is effective for inhibition of age-induced degeneration in the musculoskeletal system. PMID- 27282461 TI - Osteogenesis imperfecta due to a possible new COL1A2 mutation; the importance of phenotyping and diagnostic challenges. PMID- 27282462 TI - A rare complication after minimally invasive posterior cervical laminoforaminotomy. PMID- 27282463 TI - The autism symptom interview, school-age: A brief telephone interview to identify autism spectrum disorders in 5-to-12-year-old children. AB - This study reports on the initial validation of the Autism Symptom Interview (ASI), School-Age, a brief (15-20 min) phone interview derived from questions from the Autism Diagnostic Interview-Revised (ADI-R). The ASI, School-Age was administered by interviewers with minimal training to parents of children ages 5 to 12 who had all been previously identified with (or referred for assessment of) ASD or another neurodevelopmental disorder. Children then underwent a comprehensive assessment to determine a best-estimate clinical diagnosis of ASD (n = 159) or non-ASD (e.g. language disorder, intellectual disability, ADHD; n = 130). Clinicians who conducted the assessments were blind to ASI results. ROC analyses compared ASI scores to clinical diagnosis. Due to the small number of participants with non-ASD diagnoses who were classified as nonverbal (i.e. not yet using phrases on a daily basis), it was not possible to assess sensitivity and specificity of the nonverbal algorithm in this sample. The verbal algorithm yielded a sensitivity of 0.87 (95% CI = 0.81-0.92) and a specificity of 0.62 (95% CI = 0.53-0.70). When used in conjunction with the Autism Diagnostic Observation Schedule (ADOS), sensitivity and specificity were 0.82 (95% CI = 0.74-0.88) and 0.92 (95% CI = 0.86-0.96), respectively. Internal consistency and test-retest reliability were both excellent. Particularly for verbal school age children, the ASI may serve as a useful tool to more quickly ascertain or classify children with ASD for research or clinical triaging purposes. Additional data collection is underway to determine the utility of the ASI in children who are younger and/or nonverbal. Autism Res 2017, 10: 78-88. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 27282464 TI - A Novel Universal Detection Agent for Time-Gated Luminescence Bioimaging. AB - Luminescent lanthanide chelates have been used to label antibodies in time-gated luminescence (TGL) bioimaging. However, it is a challenging task to label directly an antibody with lanthanide-binding ligands and achieve control of the target ligand/protein ratios whilst ensuring that affinity and avidity of the antibody remain uncompromised. We report the development of a new indirect detection reagent to label antibodies with detectable luminescence that circumvents this problem by labelling available lysine residues in the linker portion of the recombinant fusion protein Linker-Protein G (LPG). Succinimide activated lanthanide chelating ligands were attached to lysine residues in LPG and Protein G (without Linker) and the resulting Luminescence-Activating (LA-) conjugates were compared for total incorporation and conjugation efficiency. A higher and more efficient incorporation of ligands at three different molar ratios was observed for LPG and this effect was attributed to the presence of eight readily available lysine residues in the linker region of LPG. These Luminescence-Activating (LA-) complexes were subsequently shown to impart luminescence (upon formation of europium(III) complexes) to cell-specific antibodies within seconds and without the need for any complicated bioconjugation procedures. The potential of this technology was demonstrated by direct labelling of Giardia cysts and Cryptosporidium oocysts in TGL bioimaging. PMID- 27282465 TI - Shigella flexneri modulates stress granule composition and inhibits stress granule aggregation. AB - Invasion and multiplication of the facultative, cytosolic, enteropathogen Shigella flexneri within the colonic epithelial lining leads to an acute inflammatory response, fever and diarrhea. During the inflammatory process, infected cells are subjected to numerous stresses including heat, oxidative stress and genotoxic stress. The evolutionarily conserved pathway of cellular stress management is the formation of stress granules that store translationally inactive cellular mRNAs and interfere with cellular signalling pathways by sequestering signalling components. In this study, we investigated the ability of S. flexneri-infected cells to form stress granules in response to exogenous stresses. We found that S. flexneri infection inhibits movement of the stress granule markers eIF3 and eIF4B into stress granules and prevents the aggregation of G3BP1 and eIF4G-containing stress granules. This inhibition occurred only with invasive, but not with non-invasive bacteria and occurred in response to stresses that induce translational arrest through the phosphorylation of eIF2alpha and by treating cells with pateamine A, a drug that induces stress granules by inhibiting the eIF4A helicase. The S. flexneri-mediated stress granule inhibition could be largely phenocopied by the microtubule-destabilizing drug nocodazole and while S. flexneri infection did not lead to microtubule depolymerization, infection greatly enhanced acetylation of alpha-tubulin. Our data suggest that qualitative differences in the microtubule network or subversion of the microtubule-transport machinery by S. flexneri may be involved in preventing the full execution of this cellular stress response. PMID- 27282466 TI - High current gain transistor laser. AB - A transistor laser (TL), having the structure of a transistor with multi-quantum wells near its base region, bridges the functionality gap between lasers and transistors. However, light emission is produced at the expense of current gain for all the TLs reported up to now, leading to a very low current gain. We propose a novel design of TLs, which have an n-doped InP layer inserted in the emitter ridge. Numerical studies show that a current flow aperture for only holes can be formed in the center of the emitter ridge. As a result, the common emitter current gain can be as large as 143.3, which is over 15 times larger than that of a TL without the aperture. Besides, the effects of nonradiative recombination defects can be reduced greatly because the flow of holes is confined in the center region of the emitter ridge. PMID- 27282467 TI - Age differences in learning emerge from an insufficient representation of uncertainty in older adults. AB - Healthy aging can lead to impairments in learning that affect many laboratory and real-life tasks. These tasks often involve the acquisition of dynamic contingencies, which requires adjusting the rate of learning to environmental statistics. For example, learning rate should increase when expectations are uncertain (uncertainty), outcomes are surprising (surprise) or contingencies are more likely to change (hazard rate). In this study, we combine computational modelling with an age-comparative behavioural study to test whether age-related learning deficits emerge from a failure to optimize learning according to the three factors mentioned above. Our results suggest that learning deficits observed in healthy older adults are driven by a diminished capacity to represent and use uncertainty to guide learning. These findings provide insight into age related cognitive changes and demonstrate how learning deficits can emerge from a failure to accurately assess how much should be learned. PMID- 27282468 TI - Nearby grandmother enhances calf survival and reproduction in Asian elephants. AB - Usually animals reproduce into old age, but a few species such as humans and killer whales can live decades after their last reproduction. The grandmother hypothesis proposes that such life-history evolved through older females switching to invest in their existing (grand)offspring, thereby increasing their inclusive fitness and selection for post-reproductive lifespan. However, positive grandmother effects are also found in non-menopausal taxa, but evidence of their associated fitness effects is rare and only a few tests of the hypothesis in such species exist. Here we investigate the grandmother effects in Asian elephants. Using a multigenerational demographic dataset on semi-captive elephants in Myanmar, we found that grandcalves from young mothers (<20 years) had 8 times lower mortality risk if the grandmother resided with her grandcalf compared to grandmothers residing elsewhere. Resident grandmothers also decreased their daughters' inter-birth intervals by one year. In contrast to the hypothesis predictions, the grandmother's own reproductive status did not modify such grandmother benefits. That elephant grandmothers increased their inclusive fitness by enhancing their daughter's reproductive rate and success irrespective of their own reproductive status suggests that fitness-enhancing grandmaternal effects are widespread, and challenge the view that grandmother effects alone select for menopause coupled with long post-reproductive lifespan. PMID- 27282469 TI - Distribution of Marburg virus in Africa: An evolutionary approach. AB - The aim of this study was to investigate the origin and geographical dispersion of Marburg virus, the first member of the Filoviridae family to be discovered. Seventy-three complete genome sequences of Marburg virus isolated from animals and humans were retrieved from public databases and analysed using a Bayesian phylogeographical framework. The phylogenetic tree of the Marburg virus data set showed two significant evolutionary lineages: Ravn virus (RAVV) and Marburg virus (MARV). MARV divided into two main clades; clade A included isolates from Uganda (five from the European epidemic in 1967), Kenya (1980) and Angola (from the epidemic of 2004-2005); clade B included most of the isolates obtained during the 1999-2000 epidemic in the Democratic Republic of the Congo (DRC) and a group of Ugandan isolates obtained in 2007-2009. The estimated mean evolutionary rate of the whole genome was 3.3*10(-4) substitutions/site/year (credibility interval 2.0 4.8). The MARV strain had a mean root time of the most recent common ancestor of 177.9years ago (YA) (95% highest posterior density 87-284), thus indicating that it probably originated in the mid-XIX century, whereas the RAVV strain had a later origin dating back to a mean 33.8 YA. The most probable location of the MARV ancestor was Uganda (state posterior probability, spp=0.41), whereas that of the RAVV ancestor was Kenya (spp=0.71). There were significant migration rates from Uganda to the DRC (Bayes Factor, BF=42.0) and in the opposite direction (BF=5.7). Our data suggest that Uganda may have been the cradle of Marburg virus in Africa. PMID- 27282470 TI - Genetic diversity in Echinococcus shiquicus from the plateau pika (Ochotona curzoniae) in Darlag County, Qinghai, China. AB - The metacestode of Echinococcus shiquicus has been recorded previously in the lung and liver of its intermediate host, the plateau pika (Ochotona curzoniae), but there is limited information regarding other organ sites. There is also limited evidence of intra-specific genetic variation within E. shiquicus. A PCR amplified mitochondrial (mt) nad1 gene fragment (approximately 1400bp in size), with unique EcoRI and SspI restriction sites, was used to distinguish cysts or cyst-like lesions of E. shiquicus from E. multilocularis. Then, the complete mt nad1 and cox1 genes for the E. shiquicus isolates were amplified and sequenced. Phylogenetic tree and haplotype network analyses for the isolates were then generated based on a concatenated dataset of the nad1 and cox1 genes using the neighbour-joining (NJ) method and TCS1.21 software. Nineteen of eighty trapped pikas were found to harbor cysts (71 in total) when dissected at the survey site. Seventeen animals had cysts (fertile) present only in the lungs, one animal had fertile cysts in the lungs and spleen, and one individual had an infertile kidney cyst. Restriction endonuclease analysis of a fragment of the nad1 gene indicated all the cysts were due to E. shiquicus. Genetic diversity analysis revealed that the nad1 and cox1 genes varied by 0.1-1.2% and 0.1-1.0%, respectively. Haplotype network analysis of the concatenated nad1 and cox1 sequences of the isolates showed they were classified into at least 6 haplotypes, and different haplotype percentages ranged from 4.2% to 29.6%. Although, high haplotype diversity was evident in the study area, the complete nad1 and cox1 gene sequences obtained indicated that all samples represented isolates of E. shiquicus. The study has also provided a new PCR-restriction endonuclease-based method to rapidly distinguish E. shiquicus from E. multilocularis which provides a useful tool for epidemiological investigations where the two species overlap. PMID- 27282471 TI - Divergent hepatitis E virus in birds of prey, common kestrel (Falco tinnunculus) and red-footed falcon (F. vespertinus), Hungary. AB - Hepatitis E virus (HEV), family Hepeviridae, has raised considerable public health concerns because of its zoonotic potential; however, the animal to animal transmissions and the natural chain of hepevirus infections in wildlife are less known. Using random amplification and next generation sequencing technology a novel HEV in birds of prey was serendipitously identified in Hungary. HEV RNA was detected in total of 2 (18%) of the 11 and 1 (14%) of the 7 faecal samples from common kestrels and red-footed falcons, respectively. High faecal viral load (2.03*10(8) genomic copies/ml) measured by qPCR. The complete genome of strain kestrel/MR22/2014/HUN (KU670940) HEV is 7033-nt long including a 35-nt 5'end and a 63-nt 3'end (excluding the poly(A)-tail). Sequence analyses indicated that the ORF1 (4920nt/639 aa), ORF2 (1989nt/662 aa) and ORF3 (360nt/119aa) proteins of kestrel/MR22/2014/HUN shared the highest identity (58.1%, 66.8% and 28.5%) to the corresponding proteins of ferret, rat and human genotype 4 Orthohepeviruses, respectively. Interestingly, the ORF3 protein is potentially initiated with leucine (L) using an alternate, non-AUG (UUG) start codon. This study reports the identification and complete genome characterization of a novel Orthohepevirus species related to mammalian HEVs in birds of prey. It is important to recognize all potential hosts, reservoirs and spreaders in nature and to reconstruct the phylogenetic history of hepeviruses. PMID- 27282472 TI - Deep sequencing increases hepatitis C virus phylogenetic cluster detection compared to Sanger sequencing. AB - Effective surveillance and treatment strategies are required to control the hepatitis C virus (HCV) epidemic. Phylogenetic analyses are powerful tools for reconstructing the evolutionary history of viral outbreaks and identifying transmission clusters. These studies often rely on Sanger sequencing which typically generates a single consensus sequence for each infected individual. For rapidly mutating viruses such as HCV, consensus sequencing underestimates the complexity of the viral quasispecies population and could therefore generate different phylogenetic tree topologies. Although deep sequencing provides a more detailed quasispecies characterization, in-depth phylogenetic analyses are challenging due to dataset complexity and computational limitations. Here, we apply deep sequencing to a characterized population to assess its ability to identify phylogenetic clusters compared with consensus Sanger sequencing. For deep sequencing, a sample specific threshold determined by the 50th percentile of the patristic distance distribution for all variants within each individual was used to identify clusters. Among seven patristic distance thresholds tested for the Sanger sequence phylogeny ranging from 0.005-0.06, a threshold of 0.03 was found to provide the maximum balance between positive agreement (samples in a cluster) and negative agreement (samples not in a cluster) relative to the deep sequencing dataset. From 77 HCV seroconverters, 10 individuals were identified in phylogenetic clusters using both methods. Deep sequencing analysis identified an additional 4 individuals and excluded 8 other individuals relative to Sanger sequencing. The application of this deep sequencing approach could be a more effective tool to understand onward HCV transmission dynamics compared with Sanger sequencing, since the incorporation of minority sequence variants improves the discrimination of phylogenetically linked clusters. PMID- 27282473 TI - Paediatric tympanoplasty: comparative study between patients aged 5-8 years and those aged over 14 years. AB - OBJECTIVE: To evaluate and analyse the success rate of tympanoplasty type I in paediatric patients aged 5 to 8 years compared to a control group (patients aged over 14 years). METHODS: In this prospective study, 60 patients (of either sex) with chronic suppurative otitis media inactive mucosal disease were divided into 2 groups (30 in each): group A comprised paediatric patients aged 5-8 years and group B consisted of older individuals aged over 14 years. All patients underwent tympanoplasty type I with an underlay technique using a temporalis fascia graft. RESULTS: Impressive surgical success rates of 87 and 90 per cent were recorded in groups A and B, respectively. Furthermore, audiological success rates of 69 and 78 per cent were achieved in groups A and B respectively. Statistical analysis of the data revealed that eustachian tube function had no impact on the outcome of tympanoplasty. CONCLUSION: Tympanoplasty type I performed in children aged five to eight years gives comparable results to those of older individuals. PMID- 27282475 TI - Reliability of graph analysis of resting state fMRI using test-retest dataset from the Human Connectome Project. AB - The exploration of brain networks with resting-state fMRI (rs-fMRI) combined with graph theoretical approaches has become popular, with the perspective of finding network graph metrics as biomarkers in the context of clinical studies. A preliminary requirement for such findings is to assess the reliability of the graph based connectivity metrics. In previous test-retest (TRT) studies, this reliability has been explored using intraclass correlation coefficient (ICC) with heterogeneous results. But the issue of sample size has not been addressed. Using the large TRT rs-fMRI dataset from the Human Connectome Project (HCP), we computed ICCs and their corresponding p-values (applying permutation and bootstrap techniques) and varied the number of subjects (from 20 to 100), the scan duration (from 400 to 1200 time points), the cost and the graph metrics, using the Anatomic-Automatic Labelling (AAL) parcellation scheme. We quantified the reliability of the graph metrics computed both at global and regional level depending, at optimal cost, on two key parameters, the sample size and the number of time points or scan duration. In the cost range between 20% to 35%, most of the global graph metrics are reliable with 40 subjects or more with long scan duration (14min 24s). In large samples (for instance, 100 subjects), most global and regional graph metrics are reliable for a minimum scan duration of 7min 14s. Finally, for 40 subjects and long scan duration (14min 24s), the reliable regions are located in the main areas of the default mode network (DMN), the motor and the visual networks. PMID- 27282474 TI - ALS and FTD: an epigenetic perspective. AB - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two fatal neurodegenerative diseases seen in comorbidity in up to 50 % of cases. Despite tremendous efforts over the last two decades, no biomarkers or effective therapeutics have been identified to prevent, decelerate, or stop neuronal death in patients. While the identification of multiple mutations in more than two dozen genes elucidated the involvement of several mechanisms in the pathogenesis of both diseases, identifying the hexanucleotide repeat expansion in C9orf72, the most common genetic abnormality in ALS and FTD, opened the door to the discovery of several novel pathogenic biological routes, including chromatin remodeling and transcriptome alteration. Epigenetic processes regulate DNA replication and repair, RNA transcription, and chromatin conformation, which in turn further dictate transcriptional regulation and protein translation. Transcriptional and post-transcriptional epigenetic regulation is mediated by enzymes and chromatin modifying complexes that control DNA methylation, histone modifications, and RNA editing. While the alteration of DNA methylation and histone modification has recently been reported in ALS and FTD, the assessment of epigenetic involvement in both diseases is still at an early stage, and the involvement of multiple epigenetic players still needs to be evaluated. As the epigenome serves as a way to alter genetic information not only during aging, but also following environmental signals, epigenetic mechanisms might play a central role in initiating ALS and FTD, especially for sporadic cases. Here, we provide a review of what is currently known about altered epigenetic processes in both ALS and FTD and discuss potential therapeutic strategies targeting epigenetic mechanisms. As approximately 85 % of ALS and FTD cases are still genetically unexplained, epigenetic therapeutics explored for other diseases might represent a profitable direction for the field. PMID- 27282477 TI - A forward modelling approach for the estimation of oxygen extraction fraction by calibrated fMRI. AB - The measurement of the absolute rate of cerebral metabolic oxygen consumption (CMRO2) is likely to offer a valuable biomarker in many brain diseases and could prove to be important in our understanding of neural function. As such there is significant interest in developing robust MRI techniques that can quantify CMRO2 non-invasively. One potential MRI method for the measurement of CMRO2 is via the combination of fMRI and cerebral blood flow (CBF) data acquired during periods of hypercapnic and hyperoxic challenges. This method is based on the combination of two, previously independent, signal calibration techniques. As such analysis of the data has been approached in a stepwise manner, feeding the results of one calibration experiment into the next. Analysing the data in this manner can result in unstable estimates of the output parameter (CMRO2), due to the propagation of errors along the analysis pipeline. Here we present a forward modelling approach that estimates all the model parameters in a one-step solution. The method is implemented using a regularized non-linear least squares approach to provide a robust and computationally efficient solution. The proposed framework is compared with previous analytical approaches using modelling studies and in vivo acquisitions in healthy volunteers (n=10). The stability of parameter estimates is demonstrated to be superior to previous methods (both in vivo and in simulation). In vivo estimates made with the proposed framework also show better agreement with expected physiological variation, demonstrating a strong negative correlation between baseline CBF and oxygen extraction fraction. It is anticipated that the proposed analysis framework will increase the reliability of absolute CMRO2 measurements made with calibrated BOLD. PMID- 27282476 TI - Multi-compartment microscopic diffusion imaging. AB - This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure. This technique can be immediately used in the clinic for the assessment of various neurological conditions, as it requires only a widely available off-the-shelf sequence with two b-shells and high-angular gradient resolution achievable within clinically feasible scan times. To demonstrate the developed method, we use high-quality diffusion data acquired with a bespoke scanner system from the Human Connectome Project. This study establishes the normative values of the new biomarkers for a large cohort of healthy young adults, which may then support clinical diagnostics in patients. Moreover, we show that the microscopic diffusion indices offer direct sensitivity to pathological tissue alterations, exemplified in a preclinical animal model of Tuberous Sclerosis Complex (TSC), a genetic multi organ disorder which impacts brain microstructure and hence may lead to neurological manifestations such as autism, epilepsy and developmental delay. PMID- 27282479 TI - Microvesicles derived from Alde-Low EPCs support the wound healing capacity of AT MSCs. AB - Mesenchymal stem cells (MSCs) are defined as multipotent cells that can give rise to various kinds of differentiated mesenchymal cells, and are thus considered to be useful for clinical therapy. However, the big hurdles of MSC therapy are the inability of MSCs to reach the appropriate tissues or sites with high efficiency and engraftment after transplantation. In this study, we investigated how adipose tissue-derived MSCs (AT-MSCs) improve their homing ability after intravenous injection. We previously found that human endothelial progenitor cells with low aldehyde dehydrogenase activity (Alde-Low EPCs) are suitable for the treatment of ischemic tissues. In addition, we demonstrated that microvesicles (MVs) derived from Alde-Low EPCs possessed the ability to improve the homing ability of non functional Alde-High EPCs, resulting in wound healing. We initially transfected MVs derived from Alde-Low EPCs (EMVs) to human AT-MSCs, which were originally unable to cure ischemic tissues by intravenous transplantation. Remarkably, AT MSC transfected EMVs dramatically repaired the ischemic skin flap compared with AT-MSC derived-MV (MMVs) transfected AT-MSCs or control AT-MSCs. We then found that the expression of CXCR4, an important chemokine receptor for cell migration, was highly elevated in EMV-transfected AT-MSCs. Moreover, AT-MSCs transfected with EMVs, but not control AT-MSCs, migrated to wound sites after intravenous injection. Consequently, CD45(+) inflammatory cells were successfully recruited at the wound sites after the injection of EMV-transfected AT-MSCs. These results demonstrate that EMVs are a useful source to improve the homing ability and wound healing ability of MSCs at the wound sites. PMID- 27282478 TI - Stimulation of triple negative breast cancer cell migration and metastases formation is prevented by chloroquine in a pre-irradiated mouse model. AB - BACKGROUND: Some triple negative breast cancer (TNBC) patients are at higher risk of recurrence in the first three years after treatment. This rapid relapse has been suggested to be associated with inflammatory mediators induced by radiation in healthy tissues that stimulate cancer cell migration and metastasis formation. In this study, the ability of chloroquine (CQ) to inhibit radiation-stimulated development of metastasis was assessed. METHODS: The capacity of CQ to prevent radiation-enhancement of cancer cell invasion was assessed in vitro with the TNBC cell lines D2A1, 4T1 and MDA-MB-231 and the non-TNBC cell lines MC7-L1, and MCF 7. In Balb/c mice, a single mammary gland was irradiated with four daily doses of 6 Gy. After the last irradiation, irradiated and control mammary glands were implanted with D2A1 cells. Mice were treated with CQ (vehicle, 40 or 60 mg/kg) 3 h before each irradiation and then every 72 h for 3 weeks. Migration of D2A1 cells in the mammary gland, the number of circulating tumor cells and lung metastasis were quantified, and also the expression of some inflammatory mediators. RESULTS: Irradiated fibroblasts have increased the invasiveness of the TNBC cell lines only, a stimulation that was prevented by CQ. On the other hand, invasiveness of the non-TNBC cell lines, which was not enhanced by irradiated fibroblasts, was also not significantly modified by CQ. In Balb/c mice, treatment with CQ prevented the stimulation of D2A1 TNBC cell migration in the pre irradiated mammary gland, and reduced the number of circulating tumor cells and lung metastases. This protective effect of CQ was associated with a reduced expression of the inflammatory mediators interleukin-1beta, interleukin-6, and cyclooxygenase-2, while the levels of matrix metalloproteinases-2 and -9 were not modified. CQ also promoted a blocking of autophagy. CONCLUSION: CQ prevented radiation-enhancement of TNBC cell invasion and reduced the number of lung metastases in a mouse model. PMID- 27282480 TI - RVX-297- a novel BD2 selective inhibitor of BET bromodomains. AB - Bromodomains are epigenetic readers that specifically bind to the acetyl lysine residues of histones and transcription factors. Small molecule BET bromodomain inhibitors can disrupt this interaction which leads to potential modulation of several disease states. Here we describe the binding properties of a novel BET inhibitor RVX-297 that is structurally related to the clinical compound RVX-208, currently undergoing phase III clinical trials for the treatment of cardiovascular diseases, but is distinctly different in its biological and pharmacokinetic profiles. We report that RVX-297 preferentially binds to the BD2 domains of the BET bromodomain and Extra Terminal (BET) family of protein. We demonstrate the differential binding modes of RVX-297 in BD1 and BD2 domains of BRD4 and BRD2 using X-ray crystallography, and describe the structural differences driving the BD2 selective binding of RVX-297. The isothermal titration calorimetry (ITC) data illustrate the related differential thermodynamics of binding of RVX-297 to single as well as dual BET bromodomains. PMID- 27282481 TI - Regulation of endothelial nitric oxide synthase activation in endothelial cells by S1P1 and S1P3. AB - Endothelial nitric oxide synthase (eNOS) plays a crucial role in vascular homeostasis. Lysophospholipid interaction with sphingosine 1-phosphat (S1P) receptors results in eNOS activation in different cells. In endothelial cells, eNOS activation via S1P1 or S1P3 was shown controversially. The aim of this study is to investigate the meaning of both S1P receptors for eNOS activation in human endothelial cells. Therefore, several S1P1 and S1P3 agonists in combination with antagonists and specific RNAi approach were used. eNOS activation was measured in human umbilical vein endothelial cells (HUVEC) via DAF2-DA-based fluorescence microscopy. For investigation of the signaling pathway, agonists/antagonist studies, RNAi approach, LuminexTM multiplex, and Western Blot were used. In HUVEC, both the S1P1 agonist AUY954 as well as the S1P1,3 agonist FTY720P induced eNOS activation in a time- and dose-dependent manner. Other S1P1 agonists activated eNOS to a lesser extent. The AUY954-induced eNOS activation was blocked by the S1P1 antagonist W146, the combination of W146 and the S1P3 antagonist CAY10444 and the S1P1,3 antagonist VPC23019, but not by CAY10444 indicating the meaning of S1P1 for the AUY954-induced eNOS activation. The FTY720P-induced eNOS activation was blocked only by the combination of W146 and CAY10444 and the combined S1P1,3 antagonist VPC23019, but not by W146 or CAY10444 indicating the importance of both S1P1 and S1P3 for FTY720-induced eNOS activation. These results were confirmed using specific siRNA against S1P1 and S1P3. The S1P1,3 activation results in Akt phosphorylation and subsequent activation of eNOS via phosphorylation at serine(1177) and dephosphorylation at threonine(495). Beside former investigations with rather unspecific S1P receptor activation these data show potent selective S1P1 activation by using AUY954 and with selective S1P receptor inhibition evidence was provided that both S1P1 and S1P3 lead to downstream activation of eNOS in HUVEC in the same experimental setting. Inhibition or knockdown of one of these receptor subtypes did not abolish the eNOS activation and subsequent NO production. PMID- 27282482 TI - Expression of inflammation-related genes in aldosterone-producing adenomas with KCNJ5 mutation. AB - BACKGROUND: The adrenocortical cells have been shown to produce various inflammatory cytokines such as TNFalpha and IL-6, which could modulate steroidogenesis. However, the role of inflammatory cytokines in aldosterone producing adenomas (APAs) is not fully understood. In the present study, we examined the relationships between mRNA expression levels of the inflammation related genes and somatic mutations in APA tissues. METHODS: We evaluated mRNA expression levels of TNFA, IL6, and NFKB1 in APA tissues obtained from 44 Japanese APA patients. RESULTS: We revealed that mRNA expression patterns of the inflammation-related genes depended on a KCNJ5 somatic mutation. In addition, we showed that mRNA expression levels of the inflammation-related genes correlated with those of the steroidogenic enzyme CYP11B1 in the patients with APAs. CONCLUSION: The present study documented for the first time the expression of inflammation-related genes in APAs and the correlation of their expression levels with the KCNJ5 mutation status and mRNA expression levels of steroidogenic enzymes, indicating the pathophysiological relevance of inflammation-related genes in APAs. PMID- 27282483 TI - Heteromeric channels with different phenotypes are generated when coexpressing two P2X2 receptor isoforms. AB - To investigate if channels with different stoichiometry are formed from P2X2 receptor isoforms during their heterologous co-expression. The two-electrode voltage-clamp technique was used to measured ATP induced currents in Xenopus laevis oocytes. We used a mutant (P2X2-2bm) because its ATP sensitivity is lower than P2X2-2b receptors, which highlights the differences with its splice variant P2X2-1a.Currents through homomeric channels had significantly different Hill coefficients. P2XR are trimeric proteins with three agonist binding sites; therefore, only two homomeric and two heteromeric stoichiometries are possible when both P2X2 isoforms are coexpressed, the heteromeric channels might be formed by: i) 2(P2X2-1a)+1(P2X2-2bm); or ii) 1(P2X2-1a)+2(P2X2-2bm). Because P2X2 channels open when two binding sites are occupied, these stoichiometries are expected to have different ATP sensitivities. Thus, co-expressing both P2X2 isoforms, two oocyte populations were distinguished based on their sensitivity to ATP and Hill coefficients. For the first population (P2X2-1a like), the ATP EC50 and the Hill coefficient were not different than those of homomeric P2X2-1a channels similarly, for the second population (P2X2-2bm like), these variables were also not different than for those of homomeric P2X2-2bm channels. Various findings indicate that homomeric channel expression is not responsible for such differences. Our observations indicate that two heteromeric channels can be assembled from two P2X2 receptor isoforms. Our data support a current model, according to which, ATP activation of two subunits can open P2X2 channel. However, PPADS appears to bind to all three subunits in order to inhibit ATP effects on P2X2 receptors. PMID- 27282484 TI - N-terminal domain of PB1-F2 protein of influenza A virus can fold into amyloid like oligomers and damage cholesterol and cardiolipid containing membranes. AB - PB1-F2 protein is a factor of virulence of influenza A viruses which increases the mortality and morbidity associated with infection. Most seasonal H1N1 Influenza A viruses express nowadays a truncated version of PB1-F2. Here we show that truncation of PB1-F2 modified supramolecular organization of the protein in a membrane-mimicking environment. In addition, full-length PB1-F2(1-90) and C terminal PB1-F2 domain (53-90), efficiently permeabilized various anionic liposomes while N-terminal domain PB1-F2(1-52) only lysed cholesterol and cardiolipin containing lipid bilayers. These findings suggest that the truncation of PB1-F2 may impact the pathogenicity of a given virus strain. PMID- 27282485 TI - Effects of environmental enrichment in aged mice on anxiety-like behaviors and neuronal nitric oxide synthase expression in the brain. AB - Previous studies have shown that an enriched environment (EE) has an important effect on brain function via the neuronal nitric oxide synthase/nitric oxide (nNOS/NO) pathway in young and aged animals. However, whether EE induces its effect by altering nNOS expression levels and whether it lowers anxiety-like behaviors in aged mice remains unclear. Here, we show that nNOS expression levels increased with age in the hippocampus and cerebellum in aged mice, but not in the cortex. Moreover, EE reduced anxiety-like behaviors in aged mice and reduced nNOS expression levels in the cerebellum, but not in the cortex. The present study suggests that EE improves anxiety-like behaviors in aged mice by altering nNOS expression levels in the hippocampus or cerebellum. PMID- 27282486 TI - Evaluation of a time efficient immunization strategy for anti-PAH antibody development. AB - The development of monoclonal antibodies (mAb) with affinity to small molecules can be a time-consuming process. To evaluate shortening the time for mAb production, we examined mouse antisera at different time points post-immunization to measure titer and to evaluate the affinity to the immunogen PBA (pyrene butyric acid). Fusions were also conducted temporally to evaluate antibody production success at various time periods. We produced anti-PBA antibodies 7 weeks post-immunization and selected for anti-PAH reactivity during the hybridoma screening process. Moreover, there were no obvious sensitivity differences relative to antibodies screened from a more traditional 18-week schedule. Our results demonstrate a more time efficient immunization strategy for anti-PAH antibody development that may be applied to other small molecules. PMID- 27282487 TI - A new ChainMail approach for real-time soft tissue simulation. AB - This paper presents a new ChainMail method for real-time soft tissue simulation. This method enables the use of different material properties for chain elements to accommodate various materials. Based on the ChainMail bounding region, a new time-saving scheme is developed to improve computational efficiency for isotropic materials. The proposed method also conserves volume and strain energy. Experimental results demonstrate that the proposed ChainMail method can not only accommodate isotropic, anisotropic and heterogeneous materials but also model incompressibility and relaxation behaviors of soft tissues. Further, the proposed method can achieve real-time computational performance. PMID- 27282488 TI - Treatment With Dithiothreitol Improves Bacterial Recovery From Tissue Samples in Osteoarticular and Joint Infections. AB - BACKGROUND: Prosthetic implants, periprosthetic and osteoarticular tissues are specimens of choice for diagnosis of bone and joint infections. Homogenization is considered the best procedure for treatment of tissues samples, but, it is not always performed in all laboratories. Dithiothreitol (DTT) has been proposed as an alternative treatment to sonication for microbiological diagnosis of prosthetic joint infections. In this study, the applicability of DTT treatment for processing of periprosthetic and osteoarticular tissues for diagnosis of bone and joint infections was evaluated and compared with normal saline solution treatment. METHODS: Periprosthetic tissue samples were collected from 70 consecutive patients (25 infected and 45 not infected). For each patient, samples from the same site were randomly allocated to DTT or saline treatment. Treated samples were centrifuged at 3000 rpm for 10 minutes. Aliquots from the concentrated samples were plated on agar plates and inoculated in broths. Sensitivity and specificity were calculated for each treatment. RESULTS: Microbial growth was observed in samples from 14 and 11 infected patients after DTT and saline treatments, respectively. Concordance between the 2 methods was observed in the 85.7% of cases. Sensitivity was 88.0% for DTT and 72.0% for saline. Specificity was 97.8% and 91.1% for DTT and saline, respectively. Treatment with DTT showed higher sensitivity and specificity with respect to the method routinely used in our laboratory. CONCLUSION: DTT treatment may be considered a practicable strategy for microbiological analysis of tissues for diagnosis of bone and joint infections. PMID- 27282490 TI - Efficacy of a Nasal Spray from Citrus limon and Cydonia oblonga for the Treatment of Hay Fever Symptoms-A Randomized, Placebo Controlled Cross-Over Study. AB - Nasal spray from lemon and quince (LQNS) is used to treat hay fever symptoms and has been shown to inhibit histamine release from mast cells in vitro. Forty-three patients with grass pollen allergy (GPA) were randomized to be treated either with placebo or LQNS for one week, respectively, in a cross-over study. At baseline and after the respective treatments patients were provoked with grass pollen allergen. Outcome parameters were nasal flow measured with rhinomanometry (primary), a nasal symptom score, histamine in the nasal mucus and tolerability. In the per protocol population absolute inspiratory nasal flow 10 and 20 min after provocation was higher with LQNS compared to placebo (-37 +/- 87 mL/s; p = 0.027 and -44 +/- 85 mL/s; p = 0.022). The nasal symptom score showed a trend (3.3 +/- 1.8 in the placebo and 2.8 +/- 1.5 in the LQNS group; p = 0.070) in favor of LQNS; the histamine concentration was not significantly different between the groups. Tolerability of both, LQNS and placebo, was rated as very good. LQNS seems to have an anti-allergic effect in patients with GPA. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27282489 TI - Tropical Drosophila pandora carry Wolbachia infections causing cytoplasmic incompatibility or male killing. AB - Wolbachia infections have been described in several Drosophila species, but relatively few have been assessed for phenotypic effects. Cytoplasmic incompatibility (CI) is the most common phenotypic effect that has been detected, while some infections cause male killing or feminization, and many Wolbachia infections have few host effects. Here, we describe two new infections in a recently described species, Drosophila pandora, one of which causes near-complete CI and near-perfect maternal transmission (the "CI" strain). The other infection is a male killer (the "MK" strain), which we confirm by observing reinitiation of male production following tetracycline treatment. No incompatibility was detected in crosses between CI strain males and MK strain females, and rare MK males do not cause CI. Molecular analyses indicate that the CI and MK infections are distantly related and the CI infection is closely related to the wRi infection of Drosophila simulans. Two population surveys indicate that all individuals are infected with Wolbachia, but the MK infection is uncommon. Given patterns of incompatibility among the strains, the infection dynamics is expected to be governed by the relative fitness of the females, suggesting that the CI infection should have a higher fitness. This was evidenced by changes in infection frequencies and sex ratios in population cages initiated at different starting frequencies of the infections. PMID- 27282491 TI - Permissive role of cytosolic pH acidification in neurodegeneration: A closer look at its causes and consequences. AB - The maintenance of cytosolic pH in its physiological range is required for normal neuronal activity, and even minor alterations can have serious consequences. This Review summarizes the current understanding of the conditions that are associated with cytosolic pH disruption and that lead to abnormal cytosolic acidification. Oxidative stress results in cytosolic acidification, and this plays a crucial role in the emergence of apoptosis in protein misfolding and excitotoxicity, ultimately leading to irreversible neuronal damage. Through the identification of mechanisms by which intraneuronal pH acidification promotes neurodegeneration, we may identify new approaches for preventing and treating neurodegenerative disorders. (c) 2016 Wiley Periodicals, Inc. PMID- 27282492 TI - Mechanical Thrombectomy for Stroke After Cardiac Surgery. AB - Stroke after cardiac surgery remains a devastating complication and its treatment options are limited. Systemic fibrinolysis is a relative contraindication, because it raises the risk of systemic hemorrhage. Endovascular therapy, mechanical thrombectomy, and intra-arterial fibrinolysis have emerged as safer options. We present three patients who developed strokes following cardiac surgery who underwent successful mechanical thrombectomy and review the literature on this subject. doi: 10.1111/jocs.12776 (J Card Surg 2016;31:517 520). PMID- 27282493 TI - Protein Complexation and pH Dependent Release Using Boronic Acid Containing PEG Polypeptide Copolymers. AB - New poly(L-lysine)-b-poly(ethylene glycol) copolypeptides have been prepared, where the side-chain amine groups of lysine residues are modified to contain ortho-amine substituted phenylboronic acid, i.e., Wulff-type phenylboronic acid (WBA), groups to improve their pH responsive, carbohydrate binding properties. These block copolymers form nanoscale complexes with glycosylated proteins that are stable at physiological pH, yet dissociate and release the glycoproteins under acidic conditions, similar to those found in endosomal and lysosomal compartments within cells. These results suggest that WBA modified polypeptide copolymers are promising for further development as degradable carriers for intracellular protein delivery. PMID- 27282494 TI - Enhanced recovery of Arcobacter spp. using NaCl in culture media and re assessment of the traits of Arcobacter marinus and Arcobacter halophilus isolated from marine water and shellfish. AB - The genus Arcobacter is a relatively poorly known group of bacteria, and the number of new species and sequences from non-culturable strains has increased considerably in recent years. This study investigates whether using media that contain NaCl might help to improve the recovery of Arcobacter spp. from marine environments. To this aim, 62 water and shellfish samples were analysed in parallel, with both a commonly used culture method (enrichment in Arcobacter-CAT broth followed by culture on Blood Agar) and a new one that supplements the Arcobacter-CAT enrichment broth with 2.5% NaCl (w/v) followed by culturing on Marine Agar. The new method yielded ca. 40% more positive samples and provided a higher diversity of known (11 vs. 7) and unknown (7 vs. 2) Arcobacter species. Among the 11 known species recovered, Arcobacter marinus and Arcobacter halophilus were isolated only by this new method. No more strains of these species have been isolated since their original descriptions, both of which were based only on a single strain. In view of that, the phenotypic characteristics of these species are re-evaluated in the present study, using the new strains. Strains of A. halophilus had the same phenotypic profile as the type strain. However, some strains of A. marinus differed from the type strain in that they did not hydrolyse indoxyl-acetate, becoming, therefore, the first Arcobacter species to show a varying ability to hydrolyse indoxyl-acetate. This study shows to what extent a simple variation to the culture media can have a big influence on positive samples and on the community of species recovered. PMID- 27282495 TI - Characterization of plant-derived carbon and phosphorus in lakes by sequential fractionation and NMR spectroscopy. AB - Although debris from aquatic macrophytes is one of the most important endogenous sources of organic matter (OM) and nutrients in lakes, its biogeochemical cycling and contribution to internal load of nutrients in eutrophic lakes are still poorly understood. In this study, sequential fractionation by H2O, 0.1M NaOH and 1.0M HCl, combined with (13)C and (31)P NMR spectroscopy, was developed and used to characterize organic carbon (C) and phosphorus (P) in six aquatic plants collected from Tai Lake (Ch: Taihu), China. Organic matter, determined by total organic carbon (TOC), was unequally distributed in H2O (21.2%), NaOH (29.9%), HCl (3.5%) and residual (45.3%) fractions. For P in debris of aquatic plants, 53.3% was extracted by H2O, 31.9% by NaOH, and 11% by HCl, with 3.8% in residual fractions. Predominant OM components extracted by H2O and NaOH were carbohydrates, proteins and aliphatic acids. Inorganic P (Pi) was the primary form of P in H2O fractions, whereas organic P (Po) was the primary form of P in NaOH fractions. The subsequent HCl fractions extracted fewer species of C and P. Some non-extractable carbohydrates, aromatics and metal phytate compounds remained in residual fractions. Based on sequential extraction and NMR analysis, it was proposed that those forms of C (54.7% of TOC) and P (96.2% of TP) in H2O, NaOH and HCl fractions are potentially released to overlying water as labile components, while those in residues are stable and likely preserved in sediments of lakes. These results will be helpful in understanding internal loading of nutrients from debris of aquatic macrophytes and their recycling in lakes. PMID- 27282496 TI - Can green structure reduce the mortality of cardiovascular diseases? AB - Previous studies have shown that green spaces are beneficial to health; however, few studies have analyzed the relationship between green structure and mortality of cardiovascular disease. Green structure may mediate the effects of air pollution and temperature on health. This work applies partial least squares (PLS) modeling to analyze the degree to which green structure reduces mortality of cardiovascular disease, using Taipei Metropolitan Area as an empirical case. In addition to clarifying the complex relationships and effects of green structure, air pollution, temperature, and mortality of cardiovascular disease, this study demonstrates that green structure has a significant influence on mortality of cardiovascular disease because it reduces the effects of air pollution and heat. The most crucial elements for planning a healthy living environment are the maximization of the largest green patch proportion and the minimization of green space fragmentation. Moreover, to enhance the benefits of greening city spaces on health, this work proposes several strategies for connecting fragmentary green spaces, expanding green patches to the largest possible proportion, and managing green spaces. The proposed strategies may serve as a reference for other metropolitan areas with features similar to those of the study area. PMID- 27282497 TI - Molecular evaluation of PIK3CA gene mutation in breast cancer: determination of frequency, distribution pattern and its association with clinicopathological findings in Indian patients. AB - Somatic mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful marker for prognosis and therapeutic target. Activating mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in 18 40 % of breast carcinomas. In this study, we evaluated PIK3CA mutation in 185 Indian breast cancer patients by direct DNA sequencing. PIK3CA mutations were observed in 23.2 % (43/185) of breast tumor samples. PIK3CA mutations were more frequent exon 30 (76.8 %) than in exon 9 (23.2 %). Mutations were mostly clustered within two hotspot region between nucleotides 1624 and 1636 or between 3129 and 3140. Sequencing analysis revealed four different missense mutations at codon 542 and 545 (E542K, E545K, E545A and E545G) in the helical domain and two different amino acid substitutions at codon 1047 (H1047R and H1047L) in the kinase domain. None of the cases harbored concomitant mutations at multiple codons. PIK3CA mutations were more frequent in older patients, smaller size tumors, ductal carcinomas, grade II tumors, lymph node-positive tumors and non DCIS tumors; however, none of the differences were significant. In addition, PIK3CA mutations were common in ER+, PR+ and HER2+ cases (30 %), and a comparatively low frequency were noted in triple-negative tumors (13.6 %). In conclusion, to our knowledge, this is the largest study to evaluate the PIK3CA mutation in Indian breast cancer patients. The frequency and distribution pattern of PIK3CA mutations is similar to global reports. Furthermore, identification of molecular markers has unique strengths and can provide insights into the pathogenic process of breast carcinomas. PMID- 27282498 TI - Pollen as a target of environmental changes. PMID- 27282500 TI - Purity of (28)Si-Enriched Silicon Material Used for the Determination of the Avogadro Constant. AB - At present, counting atoms in a one-kilogram sphere made of (28)Si-enriched silicon allows the determination of the Avogadro constant with the 2.0 * 10(-8) relative standard uncertainty required for the realization of the definition of the new kilogram. With the exception of carbon, oxygen, boron, nitrogen, and hydrogen, the claimed uncertainty is based on the postulation that the silicon material used to manufacture the sphere was above a particular level of purity. Two samples of the silicon were measured using instrumental neutron activation analysis to collect experimental data to test the purity assumption. The results obtained in two experiments carried out using different research reactor neutron sources are reported. The analysis confirmed that the silicon material was of sufficient purity by quantifying the ultratrace concentration of 12 elements and determining the detection limits of another 54 elements. PMID- 27282501 TI - Care in the last days of life. PMID- 27282502 TI - Exploring the quality of life of depressed and nondepressed, home-dwelling, Norwegian adults. AB - AIM: This study aims to explore how intimacy, physical and psychological health, loneliness, and attitudes to ageing at a time of loss affect the overall quality of life (QoL) of nondepressed and depressed older adults. METHOD: This was a randomised, stratified, cross-sectional study with two subsamples: depressed (n=74; mean: 77.9 years; 65% female) and nondepressed (n=356; mean: 75.0 years; 55% female), and based on the Geriatric Depression Scale-15. RESULTS: Physical health accounted for the greatest variance in overall QoL in the nondepressed group; psychological health, losses, and feelings of intimacy also made significant contributions. In the depressed group, intimacy made the strongest contribution, while psychological health came a close second. CONCLUSIONS: Physical health, psychological health, and loss were important to the QoL of nondepressed older adults, while intimacy was important for QoL in both depressed and nondepressed older adults. For those who are depressed, feelings of intimacy, in the form of having opportunities to express and receive love, are especially relevant and should be assessed by health professionals when planning interventions. PMID- 27282499 TI - Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5. AB - Japanese encephalitis virus (JEV) is a plus strand RNA virus, which infects brain. MicroRNAs are regulatory non-coding RNAs which regulate the expression of various genes in cells. Viruses modulate the expression of various microRNAs to suppress anti-viral signaling and evade the immune response. SOCS (Suppressor of cytokine signalling) family of proteins are negative regulators of anti-viral Jak STAT pathway. In this study, we demonstrated the regulatory role of SOCS5 in Jak STAT signaling and its exploitation by JEV through a microRNA mediated mechanism. JEV infection in human brain microglial cells (CHME3) downregulated the expression of miR-432, and upregulated SOCS5 levels. SOCS5 was validated as a target of miR-432 by using 3'UTR clone of SOCS5 in luciferase vector along with miR-432 mimic. The overexpression of miR-432 prior to JEV infection enhanced the phosphorylation of STAT1 resulting into increased ISRE activity and cellular inflammatory response resulting into diminished viral replication. The knockdown of SOCS5 resulted into increased STAT1 phosphorylation and suppressed viral replication. JEV infection mediated downregulation of miR-432 leads to SOCS5 upregulation, which helps the virus to evade cellular anti-viral response. This study demonstrated that JEV utilizes this microRNA mediated strategy to manipulate cellular immune response promoting JEV pathogenesis. PMID- 27282503 TI - Caring for carers: how community nurses can support carers of people with cancer. AB - There are more than 1 million people in the UK looking after a family member or friend with cancer, but half the number of these carers do not receive support to care. Providing this care significantly affects cancer carers emotionally, physically, and financially. Community and district nurses have a vital role to play in reaching out to these hidden carers and signposting them to the correct support. This article provides tips on identifying carers, including who they are, the challenges they face, and how health professionals can approach and speak to them. It also provides guidance on signposting carers to national and local sources of support in the UK. PMID- 27282504 TI - Exploring the opportunities and challenges of devolution and integration to community nursing. PMID- 27282505 TI - Perceptions of people living with Parkinson's disease: a qualitative study in Iran. AB - AIM: This study explores the primary concerns and perceptions of patients living with Parkinson's disease (PD). METHOD: This was an exploratory qualitative study. A purposive sample of 17 patients with PD who were attending a hospital outpatients' neurology clinic in Iran were recruited. Study data were collected through semi-structured interviews and analysed using the conventional qualitative content analysis approach. FINDINGS: We identified the 'fear of becoming disabled' as a primary concern in these patients. This concern affected the physical, emotional, mental, and social aspects of their lives. The 'fear of becoming disabled' fell into four categories, including progressive physical disability, mental alteration, decreasing social connectedness, and self-change. CONCLUSION: The study results showed that older adults with PD face a number of challenges in self-care. In addition, the 'fear of becoming disabled' was the main concern of patients with PD, particularly in late stages of the disease. PMID- 27282506 TI - Exploring the community nurse role in family-centred care for patients with dementia. AB - A diagnosis of dementia can have a significant effect, not only on the person diagnosed, but also on the person's family. Drivers within national policy and strategy to raise awareness and promote education have improved the understanding of dementia across professional groups, as well as within the wider population. However, families living with dementia still struggle to find information and support. This paper explores the common issues faced by families, and focuses on a relationship approach to care. The role of the community nurse can be central to supporting people with dementia and their families to live well in their own communities. The paper uses a case-study approach to discuss three scenarios commonly raised by family carers and people with dementia: (1) seeking help and support at point of seeking diagnosis, (2) knowing the 'right time' to seek help and advice, and (3) when symptomatic changes affect wellbeing and relationships. PMID- 27282507 TI - Mentoring students: exploring and managing incivil behaviour in community nursing placements. AB - Students who demonstrate quiet incivility can be challenging and disrupt the learning that takes place in the community setting. Recognising incivility and acting to address this behaviour with students is difficult because the behaviour is not overt or obvious to others. The most important component in attempting to manage incivility is exploring the behaviour with the student to identify the potential cause, and negotiate a strategy to improve it. It is acknowledged that the behaviour may be due to personal, academic, or professional issues. If issues are not addressed, care activity and learning are affected, and this can result in failure to achieve in practice. PMID- 27282508 TI - Death and the body as property. AB - Unlike houses or other buildings that can handed down in a will, our bodies do not have the status of property and cannot be passed on by way of gift. It is essential therefore that a testator appoints an executor who they trust to carry out the wishes of the deceased even in the face of family objection. District nurses are well placed to ensure that patients and their relatives are properly informed on how to ensure that arrangements for the disposal of the patient's body after death comply with the wishes of the patient. In this article, Richard Griffith considers the legal definition of death and the law relating to the disposal of a body after death. PMID- 27282509 TI - Competing spheres of work/life balance in palliative care. PMID- 27282510 TI - Importance of nutrition in the care of patients with diabetes. PMID- 27282511 TI - Understanding cultural needs. PMID- 27282512 TI - Lethal Epistaxis. AB - Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77 year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. PMID- 27282513 TI - Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats. AB - BACKGROUND: Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model. STUDY DESIGN AND METHODS: Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry. RESULTS: Vehicle treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury. CONCLUSIONS: These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios. PMID- 27282515 TI - A first-principles study of the diffusion coefficients of alloying elements in dilute alpha-Ti alloys. AB - Using first-principles calculations accompanied by the transition state theory and an 8-frequency model, we present a comprehensive investigation of the diffusion coefficients of substitutional alloying elements X in dilute alpha-Ti alloys, where X denotes Al, V, Nb, Ta, Mo, Zr, and Sn. The alloying elements Mo and Al exhibit a maximum and a minimum diffusion rate in dilute alpha-Ti alloys, respectively. It is found that the nearest-neighbor solute-vacancy binding energies and activation energies are roughly inversely proportional to the volume changes induced by solute atoms. There are two exceptions to this trend: Al and Mo. Besides the physical effect (i.e., solute size), two other key factors governing solute diffusion in dilute alpha-Ti are clarified: the chemical bonding characteristics and vibrational features of X-Ti pairs. It verifies that the ultrafast diffusivity of Mo arises from the interactions with Ti atoms by metallic bonds and its low-frequency contributions to lattice vibration, while the more covalent bonding nature and the high-frequency contributions to the lattice vibration of Al lead to its ultraslow diffusivity. In addition, the correlation effects of diffusion coefficients are non-negligible for the large solutes Ta, Nb, and Zr, in which the direct solute-vacancy migration barriers are much smaller than the solvent-vacancy migration barriers. PMID- 27282514 TI - Nifurtimox Is Effective Against Neural Tumor Cells and Is Synergistic with Buthionine Sulfoximine. AB - Children with aggressive neural tumors have poor survival rates and novel therapies are needed. Previous studies have identified nifurtimox and buthionine sulfoximine (BSO) as effective agents in children with neuroblastoma and medulloblastoma. We hypothesized that nifurtimox would be effective against other neural tumor cells and would be synergistic with BSO. We determined neural tumor cell viability before and after treatment with nifurtimox using MTT assays. Assays for DNA ladder formation and poly-ADP ribose polymerase (PARP) cleavage were performed to measure the induction of apoptosis after nifurtimox treatment. Inhibition of intracellular signaling was measured by Western blot analysis of treated and untreated cells. Tumor cells were then treated with combinations of nifurtimox and BSO and evaluated for viability using MTT assays. All neural tumor cell lines were sensitive to nifurtimox, and IC50 values ranged from approximately 20 to 210 MUM. Nifurtimox treatment inhibited ERK phosphorylation and induced apoptosis in tumor cells. Furthermore, the combination of nifurtimox and BSO demonstrated significant synergistic efficacy in all tested cell lines. Additional preclinical and clinical studies of the combination of nifurtimox and BSO in patients with neural tumors are warranted. PMID- 27282517 TI - Combination of organotrifluoroborates with photoredox catalysis marking a new phase in organic radical chemistry. AB - Combination of organotrifluoroborates and visible-light-driven photoredox catalysis, both of which have attracted the attention of synthetic chemists, marks a new phase in the field of organic radical chemistry. We have developed photoredox-catalyzed radical reactions with organotrifluoroborates, which turn out to serve not only as a source of organic radicals but also as radical acceptors. The first part of this Perspective deals with the generation of organic radicals from organotrifluoroborates, and the latter part describes addition of the CF3 radical to alkenyltrifluoroborates. The good chemistry between organoborates and photoredox catalysis and its future will be discussed. PMID- 27282516 TI - How different data sources and definitions of neighbourhood influence the association between food outlet availability and body mass index: a cross sectional study. AB - Inconsistencies in methodologies continue to inhibit understanding of the impact of the environment on body mass index (BMI). To estimate the effect of these differences, we assessed the impact of using different definitions of neighbourhood and data sets on associations between food outlet availability within the environment and BMI. Previous research has not extended this to show any differences in the strength of associations between food outlet availability and BMI across both different definitions of neighbourhood and data sets. Descriptive statistics showed differences in the number of food outlets, particularly other food retail outlets between different data sets and definitions of neighbourhood. Despite these differences, our key finding was that across both different definitions of neighbourhood and data sets, there was very little difference in size of associations between food outlets and BMI. Researchers should consider and transparently report the impact of methodological choices such as the definition of neighbourhood and acknowledge any differences in associations between the food environment and BMI. PMID- 27282518 TI - A nonlinear updated gain observer for MIMO systems: Design, analysis and application to marine surface vessels. AB - In this paper, the state estimation problem of a class of multi-input-multi output nonlinear systems with measurement noise is studied. We develop an extended updated-gain high gain observer to make a tradeoff between reconstruction speed and measurement noise attenuation. The designed observer, whose gains are driven by nonlinear functions of the available output estimation errors, has the ability to reconstruct system states quickly and reduce the effect of measurement noise. We establish that, if there exists a state feedback law exponentially stabilizing the system with respect to an invariant set, the estimations and estimation errors are bounded. Besides, the trajectories of state and output-feedback (based on the proposed observer) are sufficiently close, namely performance recovery. The observer performance is illustrated by various examples in marine control, including a case of transformation into the predefined structure. PMID- 27282519 TI - Reliability evaluation of auxiliary feedwater system by mapping GO-FLOW models into Bayesian networks. AB - Bayesian network (BN) is a widely used formalism for representing uncertainty in probabilistic systems and it has become a popular tool in reliability engineering. The GO-FLOW method is a success-oriented system analysis technique and capable of evaluating system reliability and risk. To overcome the limitations of GO-FLOW method and add new method for BN model development, this paper presents a novel approach on constructing a BN from GO-FLOW model. GO-FLOW model involves with several discrete time points and some signals change at different time points. But it is a static system at one time point, which can be described with BN. Therefore, the developed BN with the proposed method in this paper is equivalent to GO-FLOW model at one time point. The equivalent BNs of the fourteen basic operators in the GO-FLOW methodology are developed. Then, the existing GO-FLOW models can be mapped into equivalent BNs on basis of the developed BNs of operators. A case of auxiliary feedwater system of a pressurized water reactor is used to illustrate the method. The results demonstrate that the GO-FLOW chart can be successfully mapped into equivalent BNs. PMID- 27282521 TI - From the Editor in Chief. PMID- 27282520 TI - The role of researchers in disseminating evidence to public health practice settings: a cross-sectional study. AB - BACKGROUND: Evidence-based public health interventions, which research has demonstrated offer the most promise for improving the population's health, are not always utilized in practice settings. The extent to which dissemination from researchers to public health practice settings occurs is not widely understood. This study examines the extent to which public health researchers in the United States are disseminating their research findings to local and state public health departments. METHODS: In a 2012, nationwide study, an online questionnaire was administered to 266 researchers from the National Institutes of Health, the Centers for Disease Control and Prevention, and universities to determine dissemination practices. Logistic regression analyses were used to examine the association between dissemination to state and/or local health departments and respondent characteristics, facilitators, and barriers to dissemination. RESULTS: Slightly over half of the respondents (58%) disseminated their findings to local and/or state health departments. After adjusting for other respondent characteristics, respondents were more likely to disseminate their findings to health departments if they worked for a university Prevention Research Center or the Centers for Disease Control and Prevention, or received their degree more than 20 years ago. Those who had ever worked in a practice or policy setting, those who thought dissemination was important to their own research and/or to the work of their unit/department, and those who had expectations set by their employers and/or funding agencies were more likely to disseminate after adjusting for work place, graduate degree and/or fellowship in public health, and the year the highest academic degree was received. CONCLUSIONS: There is still room for improvement in strengthening dissemination ties between researchers and public health practice settings, and decreasing the barriers researchers face during the dissemination process. Researchers could better utilize national programs or workshops, knowledge brokers, or opportunities provided through academic institutions to become more proficient in dissemination practices. PMID- 27282522 TI - Teaching About Genetics and Sickle Cell Disease In Fifth Grade. AB - ACKNOWLEDGMENTS: We are grateful to Laura McVittie Gray for her work on the development of the student activities described in this article. This work was made possible by a Science Education Partnership Award (SEPA), Grant Number R25RR020449, from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). Additional support for this SEPA funded project was provided by Grant Number UL1RR024131-01 from NCRR. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. ABSTRACT: A 5-lesson, 5th-grade instructional unit, "Genetics and Sickle Cell Disease," was developed and tested as part of a 40-lesson curriculum entitled SEEK (Science Exploration, Excitement, and Knowledge): A Curriculum in Health and Biomedical Science for Diverse 4th and 5th Grade Students. The genetics lessons include hands-on activities (e.g., DNA extraction from cheek cells), a simulated plant genetics experiment, and a classroom visit by a person with sickle cell disease, as well as by a health care practitioner who works with sickle cell patients or a scientist specializing in genetics. The unit was tested with 82 5th-grade students at public elementary schools in Oakland, CA; 96% were racial and ethnic minorities. The comparison group consisted of 84 5th-grade Oakland students racially/ ethnically, academically, and socio-economically matched to those in the experimental group. Both groups completed a 20-question, multiple-choice pre/posttest covering science concepts, scientific process, lifestyle choices, and careers. The experimental group showed significant improvement on 13 of 20 questions (P<.05, t tests) and on the test as a whole, whereas the comparison group did not show significant improvement either on any of the questions or on the test as a whole. The experimental group improved on 10 concept questions, 2 scientific process questions, and 1 lifestyle question. Teachers rated the educational value of the unit as 9.5 on a scale from 1 (low) to 10 (high). These results show that genetics and sickle cell disease can be taught successfully in 5th grade, although they are not typically covered at this level. PMID- 27282523 TI - Prevalence of Diabetes in an Urban Hospital Emergency Room Serving Predominantly Indigenous Population. AB - OBJECTIVES: The purpose of this study was to examine the rate of diabetes and pre diabetes in previously undiagnosed individuals who came to the Detroit Receiving Hospital-Ambulatory Rapid Center (DRH-ARC), which is part of the emergency room. This region has a high minority population with over 83% being African-Americans (AAs). Diabetes screening is especially important for this population because AAs are more prone to develop complications. METHODS: Free diabetes screening was done for all patients coming to the walk in unit of the DRH-ARC. This program was supported by the "Healthy Detroit-Diabetes Initiative". The initiative was developed by the Detroit Receiving Hospital and Wayne State University Physicians Group (WSUPG) administration. RESULTS: A total of 15,971 patients, who did not have a history of diabetes, consented for screening during the period of March 2010 through March 2014. A total of 6,149 (38.5%) patients were found to have HbAlc values in the range of pre-diabetes or diabetes. The prevalence of diabetes increased with age in both men and women. The data showed high prevalence of undiagnosed pre-diabetes and diabetes in this population approaching 31% and 8%, respectively. Among patients with elevated blood pressure 41.2% had abnormal HbAlc values. In contrast, 32% of patients with normal blood pressure had abnormal HbAlc values. CONCLUSION: Continued screening of population at risk for diabetes is essential. Public health awareness programs, such as the Healthy Detroit-Diabetes Initiative should be initiated in similar areas where minority populations are prevalent. PMID- 27282524 TI - Long Term Outcomes of a Curriculum on Care for the Underserved. AB - ACKNOWLEDGEMENTS: This work was funded by HRSA grants D16HP00067 and D08PE50097. BACKGROUND: Evaluations of curricula to enhance ability to care for the underserved are often limited to short-term medical student outcomes. PURPOSE: This study evaluates retention of short-term improvements in outcomes from post curriculum to graduation. METHODS: Third-year students on 2003-2004 pediatric clerkships were randomized to a curriculum on caring for the underserved in one of three formats: established "readings only", faculty-led, or web-based. Outcomes (knowledge, attitudes, self-efficacy and clinical skills) were assessed at three timepoints-pre- and post-curriculum and at graduation. Analyses, from 2009-2010, included Fisher's exact test to assess the relationship of curriculum group with response patterns, demographics, and outcomes at graduation. Multivariate regression was used to model the longitudinal relationship between outcomes and curriculum groups, adjusting for prior clerkship experiences, baseline scores, and clustering by student. RESULTS: Of 137 students, 135 (99%) completed the pre-curriculum survey, 128 (93%) completed the post-curriculum survey and 88 (64%) completed the graduation survey. Post-curriculum improvements in self-efficacy and clinical skills seen among students receiving the faculty led or web-based curricula were retained at graduation. At graduation, web-based curriculum students' self-efficacy was significantly greater for "establishing achievable goals with underserved families" compared to established curriculum students. With regard to skills relevant to caring for the underserved, few graduates had facilitated a referral to Women, Infants and Children (33%) or followed up to ensure a patient accessed a needed resource (56%). CONCLUSIONS: Self-efficacy and skills gained through web-based and faculty-led curricula were retained at graduation. Data from items at graduation support targeted curricular improvement. PMID- 27282525 TI - Use of a Computer Program for Advance Care Planning with African American Participants. AB - ACKNOWLEDGMENTS: The authors wish to acknowledge the support and assistance of Dr. William Lawrence for his contribution to the M.A.UT model used in the decision aid, Making Your Wishes Known: Planning Your Medical Future (MYWK), Dr. Cheryl Dellasega for her leadership in focus group activities, Charles Sabatino for his review of legal aspects of MYWK, Dr. Robert Pearlman and his collaborative team for use of the advance care planning booklet "Your Life, Your Choices," Megan Whitehead for assistance in grant preparation and project organization, and the Instructional Media Development Center at the University of Wisconsin as well as JPL Integrated Communications for production and programming of MYWK. BACKGROUND: For various cultural and historical reasons, African Americans are less likely than Caucasians to engage in advance care planning (ACP) for healthcare decisions. PURPOSE: This pilot study tested whether an interactive computer program could help overcome barriers to effective ACP among African Americans. METHODS: African American adults were recruited from traditionally Black churches to complete an interactive computer program on ACP, pre-/post-questionnaires, and a follow-up phone interview. RESULTS: Eighteen adults (mean age =53.2 years, 83% female) completed the program without any problems. Knowledge about ACP significantly increased following the computer intervention (44.9% -> 61.3%, p=0.0004), as did individuals' sense of self determination. Participants were highly satisfied with the ACP process (9.4; 1 = not at all satisfied, 10 = extremely satisfied), and reported that the computer generated advance directive accurately reflected their wishes (6.4; 1 = not at all accurate, 7 = extremely accurate). Follow-up phone interviews found that >80% of participants reported having shared their advance directives with family members and spokespeople. CONCLUSION: Preliminary evidence suggests that an interactive computer program can help African Americans engage in effective advance care planning, including creating an accurate advance directive document that will be shared with loved ones. PMID- 27282527 TI - Environmental Justice and Health Effects of Urban Air Pollution. AB - PURPOSE: Minority communities often bear the burden of "hosting" pollution sources. This report assesses whether there are any health effects from living near such pollution sources and whether health effects of pollution vary by sex, ethnicity, or income. METHODS: The air pollution emissions from Hartford area, point sources are modeled and exposures are estimated for the residents who participated in a geographically-based health survey. The pollution intensities and other individual and neighborhood characteristics are used to predict an individual's reported respiratory problems. RESULTS: The results indicate that respiratory problems are correlated significantly with pollution levels, especially sulfur dioxide from the local trash-to-energy incinerator-the fifth largest one in the U.S. The effects of a given pollution level tend to be more serious for specific subgroups based upon sex, ethnicity, poverty, and age. CONCLUSION: Even when controlling for other factors, air pollution levels are significantly correlated with health problems, especially for Hispanics. This air pollution may contribute to health disparities. PMID- 27282528 TI - Race/Ethnicity in Atrial Fibrillation Stroke: Epidemiology and Pharmacotherapy. AB - The authors acknowledge the writing and editorial assistance of Rosemary Perkins of Envision Pharma Group, whose services were funded by Boehringer Ingelheim Pharmaceuticals, Inc. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), were fully responsible for all content and editorial decisions, and were involved in at all stages of manuscript development. The authors received no compensation related to the development of the manuscript. PMID- 27282529 TI - The Death of Burghardt Du Bois, 1899; Implications for Today. AB - ACKNOWLEDGEMENTS: Laura Dattner, John Krai and Linda Oppenheim provided assistance in obtaining archival material and manuscript review. Edwin Rosenthal's decedents, Robert, Eleanore Jane and Edwin Rosenthal II, provided information about their distinguished grandfather's life and commitments. Linda Oppenheim, Michael Angelo, Jessica Lydon, and Sofie Serada, archivists at Princeton University, Thomas Jefferson University, Temple University, and the College of Physicians of Philadelphia provided access to material on Edwin Rosenthal and medical care in Philadelphia at the turn of the 20th century. We thanks Laura Dattner, John Krai and Linda Oppenheim for their manuscript review. BACKGROUND: The Souls of Black Folks, W. E. B. Du Bois' compelling narrative from 1903, includes a description of the death of his only son, Burghardt. His death was caused by diphtheria and occurred in Atlanta, GA in the year 1899. Mortality from diphtheria had fallen precipitously in the mid-1890s, but neither city of Atlanta nor Philadelphia, from which the family had recently moved, had made the diphtheria antitoxin available for general use. OBJECTIVES: To identify factors affecting availability diphtheria treatment in the two cities the Du Bois family lived in and to address implications for immunization policies today. METHODS: We reviewed data and observations from medical texts and articles from the turn of the 20th century, health department records, archives of newspapers and Du Bois' writings. RESULTS: Mortality from diphtheria dropped precipitously at the end of the 19th century with the introduction of laryngecostomy and a diphtheria antitoxin. However these measures required action by health departments and was dependent on the availability of physicians and medical facilities. Lack of Public Health Departments put all southerners at risk for infectious illnesses. With respect to diphtheria, there was neither an available supply of antitoxin nor physician care available. Philadelphia may have been too mired in corruption to provide antitoxin. Burghardt lived in close proximity to a facility where antitoxin was available, data suggests he would have received appropriate treatment there and was likely to have survived. Similar phenomena-disinterest and dysfunction-affect provision of immunization for children today. Currently, availability of immunization is affected by ethnicity, income levels and immigration status. PMID- 27282530 TI - Effect of the stiffness of bone substitutes on the biomechanical behaviour of femur for core decompression. AB - Core decompression is the most common procedure for treatment of the early stages of osteonecrosis of the femoral head. The purpose of this study was to compare the biomechanical performance of four different bone graft substitutes combined with core decompression. Subject-specific finite element models generated from computed tomography (CT) scan data were used for a comprehensive analysis. Two different contact conditions were simulated representing states of osseointegration at the interface. Our results showed that the use of a low stiffness bone substitute did not increase the risk of femoral fracture in the early postoperative phase, but resulted in less micromotion and interfacial stresses than high-stiffness bone substitutes. PMID- 27282531 TI - Photo-patch and patch tests in patients with dermatitis over the photo-exposed areas: A study of 101 cases from a tertiary care centre in India. AB - BACKGROUND: Many patients with dermatitis over photo-exposed body areas are positive to many contact allergens and have a pre-existing allergic contact dermatitis. METHODS: This study included patients who presented to a tertiary centre in India with dermatitis on photo-exposed body areas suspected of chronic actinic dermatitis. Their detailed histories were recorded and cutaneous and systemic examinations were performed. Patch testing was done in all the patients and photo-patch testing was carried out in 86 patients. RESULTS: Altogether 101 patients were included (69 males, 32 females). The most common presentation was lichenified hyperpigmented plaques on the photo-exposed sites. Photosensitivity was recorded in 64 (63%) patients and summer exacerbation in 52 (52%). Exposure to the Parthenium hysterophorus weed was recorded in 70 (69%) patients, 27 (26.7%) had a history of hair dye application and 20 (20%) had a history of atopy. Photo-patch test was positive in 11 (12.8%) patients and patch testing was positive in 71 (70%). Parthenium hysterophorus was the most common allergen implicated and was positive in three (4%) photo-patch and 52 (52%) patch tests. Other positive photo-patch test allergens were perfume mix, balsam of Peru, thiuram mix, Compositae mix and promethazine hydrochloride. Other common patch test allergens were parthenolide, colophony, fragrance mix and p-phenylenediamine (PPD) base. CONCLUSION: In the Indian population parthenium and perfume mix are the most common photoallergens in patients with dermatitis over photo-exposed areas, while parthenium, colophony, fragrance mix and PPD are the common positive allergens. PMID- 27282532 TI - Smart Implants as a Novel Strategy to Regenerate Well-Founded Cartilage. AB - Here we explore a new generation of smart, living implants, combining not only active therapeutics but also stem cells, as a novel strategy to regenerate stabilised cartilage and avoid prostheses. This process can regenerate the subchondral bone foundation, which is currently difficult in the clinic. PMID- 27282533 TI - Influence of relative humidity during coating on polymer deposition and film formation. AB - The influence of relative humidity in the pan during coating on polymer deposition and film formation was investigated. Four tablet substrates, differing in hydrophobicity, porosity, and surface roughness, were prepared and coated with Eudragit((r)) RS/RL 30 D (8:2 ratio). The spray rate and atomization air pressure were varied to create two distinct micro-environmental conditions in the coating pan. PyroButton data logging devices placed directly in the pan were found to more accurately reflect the relative humidity to which tablets were exposed in comparison to measurements taken at the exhaust. Polymer deposition was shown to be influenced by the properties of the substrate, rather than the processing conditions used during coating, with higher polymer weight gains observed for the more porous tablets. Differences in the film-tablet interface and in the release performance of the coated products, however, were attributed to both the relative humidity in the pan and tablet porosity. Overall, this study demonstrated that a more humid coating process (86% vs 67%) promoted surface dissolution and physical mixing of the tablet ingredients with the forming film and the extent of this phenomenon was dependent on the tablet porosity. PMID- 27282534 TI - Design and optimization of novel paclitaxel-loaded folate-conjugated amphiphilic cyclodextrin nanoparticles. AB - As nanomedicines are gaining momentum in the therapy of cancer, new biomaterials emerge as alternative platforms for the delivery of anticancer drugs with bioavailability problems. In this study, two novel amphiphilic cyclodextrins (FCD 1 and FCD-2) conjugated with folate group to enable active targeting to folate positive breast tumors were introduced. The objective of this study was to develop and characterize new folated-CD nanoparticles via 3(2) factorial design for optimal final parameters. Full physicochemical characterization studies were performed. Blank and paclitaxel loaded FCD-1 and FCD-2 nanoparticles remained within the range of 70-275nm and 125-185nm, respectively. Zeta potential values were neutral and -20mV for FCD-1 and FCD-2 nanoparticles, respectively. Drug release studies showed initial burst release followed by a longer sustained release. Blank nanoparticles had no cytotoxicity against L929 cells. T-47D and ZR 75-1 human breast cancer cells with different levels of folate receptor expression were used to assess anti-cancer efficacy. Through targeting the folate receptor, these nanoparticles were efficiently engulfed by the breast cancer cells. Additionally, breast cancer cells became more sensitive to cytotoxic and/or cytostatic effects of PCX delivered by FCD-1 and FCD-2. In conclusion, these novel folate-conjugated cyclodextrin nanoparticles can therefore be considered as promising alternative systems for safe and effective delivery of paclitaxel with a folate-dependent mechanism. PMID- 27282535 TI - Effect of co-solutes and process variables on crystallinity and the crystal form of freeze-dried myo-inositol. AB - The purpose of this study was to elucidate how co-solutes affect the crystallization of small solute molecules during freeze-drying and subsequent storage. Crystallization profiles of myo-inositol and its mixture with dextran 40k in frozen solutions and dried solids were assessed by thermal analysis (DSC), powder-X-ray diffraction, and simultaneous DSC and PXRD analysis. Higher mass ratios of dextran maintained myo-inositol in the non-crystalline mixture state, in frozen solutions, during freeze-drying process, and exposure of dried solids to higher temperatures. Co-lyophilization with a lower mass ratio of dextran resulted in solids containing a variety of myo-inositol crystal forms and crystallinity depending on the composition and thermal history of the process. Heating of some inositol-rich amorphous solids showed crystallization of myo inositol in the metastable form and its transition to stable form before melting. Heat-treatment of inositol-rich frozen solutions resulted in high crystallinity stable-form inositol solids, leaving dextran in the amorphous state. Sufficient direct molecular interactions (e.g., hydrogen bonding) should explain the stability of dextran-rich amorphous solids. Optimizing solute composition and processes should be a potent way to control crystal form and crystallinity of components in freeze-dried formulations. PMID- 27282536 TI - Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins. AB - Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake. PMID- 27282537 TI - Apomorphine and its esters: Differences in Caco-2 cell permeability and chylomicron affinity. AB - Oral delivery of apomorphine via prodrug principle may be a potential treatment for Parkinson's disease. The purpose of this study was to investigate the transport and stability of apomorphine and its esters across Caco-2 cell monolayer and their affinity towards chylomicrons. Apomorphine, monolauroyl apomorphine (MLA) and dilauroyl apomorphine (DLA) were subjected to apical to basolateral (A-B) and basolateral to apical (B-A) transport across Caco-2 cell monolayer. The stability of these compounds was also assessed by incubation at intestinal pH and physiological pH with and without Caco-2 cells. Molecular dynamics (MD) simulations were performed to understand the stability of the esters on a molecular level. The affinity of the compounds towards plasma derived chylomicrons was assessed. The A-B transport of intact DLA was about 150 times lower than the transport of apomorphine. In contrast, MLA was highly unstable in the aqueous media leading to apomorphine appearance basolaterally. MD simulations possibly explained the differences in hydrolysis susceptibilities of DLA and MLA. The affinity of apomorphine diesters towards plasma derived chylomicrons provided an understanding of their potential lymphatic transport. The intact DLA transport is not favorable; therefore, the conversion of DLA to MLA is an important step for intestinal apomorphine absorption. PMID- 27282538 TI - Targeted chitosan-based bionanocomposites for controlled oral mucosal delivery of chlorhexidine. AB - The purpose of this study was to develop sustained release systems based on chitosan (CS) and montmorillonite (MMT) for chlorhexidine (CLX). Nanocomposites were prepared by ion-exchange. CLX systems were characterized by X-ray powder diffraction (XRD), thermal analysis (TGA), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-ray fluorescence analysis (XRF). The mucoadhesion properties of CLX nanocomposites were evaluated by SEM. The release behavior of these systems was also studied by the dialysis technique. The antibacterial activity was investigated in vitro by the disk diffusion test. Results showed long-term sustained release of CLX from the hybrid carriers without initial burst release. The release profiles of CLX from the carriers suggested the diffusion through a swollen matrix and water filled pores as the controlled drug release mechanism. The CLX hybrid nanosystem containing the positively-charged chitosan exhibited good mucoadhesion properties maintaining the CLX antimicrobial properties. PMID- 27282539 TI - Resveratrol cocrystals with enhanced solubility and tabletability. AB - Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development. PMID- 27282540 TI - Pore blocking: An innovative formulation strategy for the design of alcohol resistant multi-particulate dosage forms. AB - In this work calcium stearate (CaSt) multi-particulates loaded with codeine phosphate (COP) were developed in an attempt to provide extended release (ER) combined with alcohol dose dumping (ADD) resistance. The pellets were prepared via wet/extrusion spheronization and ER characteristics were obtained after fluid bed drying at 30 degrees C. Pore blockers (i.e., xanthan, guar gum and TiO2) were integrated to control the uptake of ethanolic media, the CaSt swelling and consequently, the COP release. While all three pore blockers are insoluble in ethanol, xanthan dissolves, guar gum swells and TiO2 does not interact with water. The incorporation of 10 and 15% TiO2 still provided ER characteristics and yielded ADD resistance in up to 40v% ethanol. The in-vitro data were subjected to PK simulations, which revealed similar codeine plasma levels when the medication is used concomitantly with alcoholic beverages. Taken together the in-vitro and in-silico results demonstrate that the incorporation of appropriate pore blockers presents a promising strategy to provide ADD resistance of multi-particulate systems. PMID- 27282541 TI - Lasting mantle scars lead to perennial plate tectonics. AB - Mid-ocean ridges, transform faults, subduction and continental collisions form the conventional theory of plate tectonics to explain non-rigid behaviour at plate boundaries. However, the theory does not explain directly the processes involved in intraplate deformation and seismicity. Recently, damage structures in the lithosphere have been linked to the origin of plate tectonics. Despite seismological imaging suggesting that inherited mantle lithosphere heterogeneities are ubiquitous, their plate tectonic role is rarely considered. Here we show that deep lithospheric anomalies can dominate shallow geological features in activating tectonics in plate interiors. In numerical experiments, we found that structures frozen into the mantle lithosphere through plate tectonic processes can behave as quasi-plate boundaries reactivated under far-field compressional forcing. Intraplate locations where proto-lithospheric plates have been scarred by earlier suturing could be regions where latent plate boundaries remain, and where plate tectonics processes are expressed as a 'perennial' phenomenon. PMID- 27282543 TI - When group members go against the grain: An ironic interactive effect of group identification and normative content on healthy eating. AB - Three studies were conducted to examine the effect of group identification and normative content of social identities on healthy eating intentions and behaviour. In Study 1 (N = 87) Australian participants were shown images that portrayed a norm of healthy vs. unhealthy behaviour among Australians. Participants' choices from an online restaurant menu were used to calculate energy content as the dependent variable. In Study 2 (N = 117), female participants were assigned to a healthy or unhealthy norm condition. The dependent variable was the amount of food eaten in a taste test. Social group identification was measured in both studies. In Study 3 (N = 117), both American identification and healthiness norm were experimentally manipulated, and participants' choices from an online restaurant menu constituted the dependent variable. In all three studies, the healthiness norm presented interacted with participants' group identification to predict eating behaviour. Contrary to what would be predicted under the traditional normative social influence account, higher identifiers chose higher energy food from an online menu and ate more food in a taste test when presented with information about their in-group members behaving healthily. The exact psychological mechanism responsible for these results remains unclear, but the pattern of means can be interpreted as evidence of vicarious licensing, whereby participants feel less motivated to make healthy food choices after being presented with content suggesting that other in-group members are engaging in healthy behaviour. These results suggest a more complex interplay between group membership and norms than has previously been proposed. PMID- 27282545 TI - Clinical Spectroscopy: general discussion. PMID- 27282544 TI - Characterization of GPR101 transcript structure and expression patterns. AB - We recently showed that Xq26.3 microduplications cause X-linked acrogigantism (X LAG). X-LAG patients mainly present with growth hormone and prolactin-secreting adenomas and share a minimal duplicated region containing at least four genes. GPR101 was the only gene highly expressed in their pituitary lesions, but little is known about its expression patterns. In this work, GPR101 transcripts were characterized in human tissues by 5'-Rapid Amplification of cDNA Ends (RACE) and RNAseq, while the putative promoter was bioinformatically predicted. We investigated GPR101 mRNA and protein expression by RT-quantitative PCR (qPCR), whole-mount in situ hybridization, and immunostaining, in human, rhesus monkey, rat and zebrafish. We identified four GPR101 isoforms characterized by different 5'-untranslated regions (UTRs) and a common 6.1kb long 3'UTR. GPR101 expression was very low or absent in almost all adult human tissues examined, except for specific brain regions. Strong GPR101 staining was observed in human fetal pituitary and during adolescence, whereas very weak/absent expression was detected during childhood and adult life. In contrast to humans, adult monkey and rat pituitaries expressed GPR101, but in different cell types. Gpr101 is expressed in the brain and pituitary during rat and zebrafish development; in rat pituitary, Gpr101 is expressed only after birth and shows sexual dimorphism. This study shows that different GPR101 transcripts exist and that the brain is the major site of GPR101 expression across different species, although divergent species- and temporal-specific expression patterns are evident. These findings suggest an important role for GPR101 in brain and pituitary development and likely reflect the very different growth, development and maturation patterns among species. PMID- 27282547 TI - Ultra-doped n-type germanium thin films for sensing in the mid-infrared. AB - A key milestone for the next generation of high-performance multifunctional microelectronic devices is the monolithic integration of high-mobility materials with Si technology. The use of Ge instead of Si as a basic material in nanoelectronics would need homogeneous p- and n-type doping with high carrier densities. Here we use ion implantation followed by rear side flash-lamp annealing (r-FLA) for the fabrication of heavily doped n-type Ge with high mobility. This approach, in contrast to conventional annealing procedures, leads to the full recrystallization of Ge films and high P activation. In this way single crystalline Ge thin films free of defects with maximum attained carrier concentrations of 2.20 +/- 0.11 * 10(20) cm(-3) and carrier mobilities above 260 cm(2)/(V.s) were obtained. The obtained ultra-doped Ge films display a room temperature plasma frequency above 1,850 cm(-1), which enables to exploit the plasmonic properties of Ge for sensing in the mid-infrared spectral range. PMID- 27282546 TI - BRAT1 mutations present with a spectrum of clinical severity. AB - Mutations in BRAT1, encoding BRCA1-associated ATM activator 1, are associated with a severe phenotype known as rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL; OMIM # 614498), characterized by intractable seizures, hypertonia, autonomic instability, and early death. We expand the phenotypic spectrum of BRAT1 related disorders by reporting on four individuals with various BRAT1 mutations resulting in clinical severity that is either mild or moderate compared to the severe phenotype seen in RMFSL. Representing mild severity are three individuals (Patients 1-3), who are girls (including two sisters, Patients 1-2) between 4 and 10 years old, with subtle dysmorphisms, intellectual disability, ataxia or dyspraxia, and cerebellar atrophy on brain MRI; additionally, Patient 3 has well-controlled epilepsy and microcephaly. Representing moderate severity is a 15-month-old boy (Patient 4) with severe global developmental delay, refractory epilepsy, microcephaly, spasticity, hyperkinetic movements, dysautonomia, and chronic lung disease. In contrast to RMFSL, his seizure onset occurred later at 4 months of age, and he is still alive. All four of the individuals have compound heterozygous BRAT1 mutations discovered via whole exome sequencing: c.638dupA (p.Val214Glyfs*189); c.803+1G>C (splice site mutation) in Patients 1-2; c.638dupA (p.Val214Glyfs*189); c.419T>C (p.Leu140Pro) in Patient 3; and c.171delG (p.Glu57Aspfs*7); c.419T>C (p.Leu140Pro) in Patient 4. Only the c.638dupA (p.Val214Glyfs*189) mutation has been previously reported in association with RMFSL. These patients illustrate that, compared with RMFSL, BRAT1 mutations can result in both moderately severe presentations evident by later-onset epilepsy and survival past infancy, as well as milder presentations that include intellectual disability, ataxia/dyspraxia, and cerebellar atrophy. (c) 2016 Wiley Periodicals, Inc. PMID- 27282548 TI - Putting a face and context on pediatric surgery cancelations: The development of parent personas to guide equitable surgical care. AB - Last-minute cancelation of planned surgery can have substantial psychological, social, and economic effects for patients/families and also leads to wastage of expensive health-care resources. In order to have a deeper understanding of the contextual, psychological, practical, and behavioral factors that potentially impact pediatric surgery cancelation, we conducted a qualitative study to create 'personas' or fictional portraits of parents who are likely to cancel surgery. We conducted in-depth qualitative interviews with 21 parents of children who were considered 'at risk' for surgical cancelation and whose scheduled surgery was canceled at late notice. From the themes, patterns, and associated descriptive phrases in the data, we developed and validated five different personas of typical scenarios reflecting parent experiences with surgery and surgery cancelations. The personas are being employed to guide contextualized development of interventions tailored to prototypical families as they prepare and attend for surgery. PMID- 27282549 TI - Peri-operative transfusion risk in classic bladder exstrophy closure: Results from a national database review. AB - OBJECTIVE: Classic bladder exstrophy (CBE) is one of the most complex pediatric urologic conditions, with patients often requiring multiple procedures throughout their lives. Patients undergoing these complex surgeries may require blood transfusion, exposing them to the risks of transfusion including antibody reactions, transmission of infectious diseases, and transfusion-related immunomodulation. We sought to determine the prevalence of and risk factors for peri-operative transfusion in patients undergoing closure for CBE. Because of the complexity of CBE management, we hypothesized that a significant number of patients undergoing closure of CBE would require peri-operative transfusion. METHOD: Patients undergoing CBE closure between 2012 and 2014 were retrospectively identified by Current Procedure Terminology codes from The National Surgical Quality Improvement Program Pediatric database, which includes data from 64 participating hospitals. Patient demographics, pre-operative characteristics including comorbidities, intra-operative characteristics, and post-operative outcomes were analyzed for associations with transfusion requirement intra-operatively or in the first 72 h post-operatively. RESULTS: Seventy-eight patients met our criteria, of whom 45 (57.7%) underwent transfusion. Patient characteristics and outcomes are noted in the Table. There was no difference between the groups in terms of age or gender. Patients who underwent transfusion were more likely to be over 3 days of age than those who did not (93.3% versus 75.8%; p = 0.046). Transfused patients were also more likely to have undergone osteotomy (82.2% versus 48.5%; p = 0.002), had an external fixation (46.7% versus 6.1%; p < 0.001), had longer median operative times (447 versus 295 min; p < 0.001), and had longer median post-operative lengths of stay (LOS) (35 versus 17 days; p = 0.003). There was no difference between the groups in terms of pre-operative risk factors or post-operative complications. CONCLUSIONS: A significant number of patients undergoing CBE closure required transfusion in the peri-operative period (57.7%). Patient characteristics found to have a higher rate of transfusion included osteotomy, external fixation, increased operative times, and longer post-operative LOS. In children undergoing closure for CBE, a large number require transfusion. The rate of transfusion is greater in older children and children undergoing osteotomy. Although osteotomy has a potentially important clinical role, especially in older patients, this study emphasizes the need for proper family counseling to include the increased likelihood of a blood transfusion and the risks associated with blood transfusion if osteotomies are performed. PMID- 27282550 TI - Long-term outcome after urinary diversion using the ileocecal segment in children and adolescents: Complications of the efferent segment. AB - INTRODUCTION: Long-term outcomes are of special concern in children after urinary diversion. In a single institution study we evaluated retrospectively the long term outcomes of urinary diversion in children, in whom the ileocecal segment had been used, in respect to complications of the efferent segment. METHODS: The Mainz pouch was used in 107 children for continent urinary diversion. Indications were neurogenic bladder (53%, 57/107), exstrophy-epispadias complex (25%, 27/107), malignancy (13%, 14/107), and others (9%, 9/107). Continent cutaneous diversion was performed in 95 patients, and 12 patients received bladder augmentation/substitution with a continent cutaneous stoma. As efferent segment, we used the in situ submucosally embedded appendix in 55/107, and an intussuscepted ileal nipple valve in 45/107 patients, other in seven patients. Complication rates and degree of satisfaction with urinary diversion were evaluated by assessing medical records and using follow-up questionnaires. RESULTS AND DISCUSSION: The median follow-up time was 15.9 years (0.4-27.6 years). There was a significant difference between the stenosis rates of appendical stoma and the intussuscepted ileal nipple valve. In general, 38% of patients (41/107) with a continent cutaneous stoma developed a stoma stenosis at the skin level, with 41% (17/41) of those having recurrent stenoses (2-6*). Of the patients with an appendix stoma, 49% (27/55) developed a stenosis, compared with 20% (9/45) of those with an intussuscepted ileal nipple valve (p < 0.001). In an attempt to reduce the incidence of stenosis, we implemented use of the ACE stopper during the last 2 years, but whether this is successful is subject to further investigations. For surgical treatment of stoma stenosis, reanastomosis of the efferent segment to the skin (n = 37, re-stenosis rate 37%, [14/37]) was superior to endoscopic scar incision (n = 44, re-stenosis rate 59% [26/44], OR 2.4). The overall continence rate was 85% (91/107). At the latest follow-up, 89% (49/55) of patients with an appendix stoma and 82% (37/45) of those with an intussuscepted ileal nipple valve were completely continent. CONCLUSION: The in situ submucosally embedded appendix and the intussuscepted ileal nipple valve are reliable continence mechanisms in the long-term median follow-up of nearly 16 years. The stomal stenosis rate is approximately double for the submucosal appendix, likely because of its smaller diameter in comparison with the ileal valve. Although we encountered a high overall rate of complications, the satisfaction rate with the diversion was high (99% [88/89] satisfied or very satisfied patients). PMID- 27282551 TI - Combined low-dose antimuscarinics for refractory detrusor overactivity in children. AB - INTRODUCTION AND AIMS: Behavioral therapy and bowel management are the initial and mainstay treatments for overactive bladder (OAB). Antimuscarinic agents are initiated if these measures fail or symptoms are severe. This study reported the results of treatment with a high dosage of a single drug in children with refractory detrusor overactivity (DO). After the children maintained their previous antimuscarinic medication, a second antimuscarinic drug (trospium chloride) was added as a combination therapy. MATERIALS AND METHOD: Seventy-two children with DO were enrolled in this prospective study (Figure). They had persistent urgency and urgency urinary incontinence (UUI), even with behavioral bowel therapy, and used an optimized dosage of oxybutynine. All patients demonstrated DO at urodynamic study and started on oxybutynin and trospium chloride at the lowest weight-adjusted dose (10-20 mg/day for trospium chloride). A bladder diary was recorded for 3 days, and urodynamic studies were repeated at 3 and 6 months. RESULTS: Sixteen children (22.2%) became dry. Thirty-three children (45.8%) attained a significant decrease in incontinence from an average of 5 to 1.3 episodes per day. A statistically significant increase of mean cystometeric bladder capacity (P = 0.006) was also observed at the 6-month follow up. The overall success rate was 68%, since 23 children (32%) discontinued combined treatment due to persistent symptoms and/or intolerable side effects. A total of 41 children (57%) reported no side effects, 25 (34.7%) reported mild side effects, six (8.3%) reported moderate side effects, and two withdrew from the study due to their side effects. CONCLUSIONS: The addition of low-dose trospium chloride to oxybutynine seemed to be an effective and safe treatment approach for children with DO who were refractory to high-dosage monotherapy. Different combinations with different antimuscarinics drugs could be evaluated in the future. PMID- 27282552 TI - Look Who's Talking: Comparing Perceptions Versus Direct Observations in Family Centered Rounds. AB - BACKGROUND AND OBJECTIVES: Family-centered rounds (FCR) are an important and recommended component of pediatric hospital care. This study compares direct observations versus perceptions and ideals of who talks during FCR. METHODS: A silent investigator observed FCR and noted who spoke, time in patient rooms, nurse and family presences, and patient information. After the observation period, the medical team was offered an anonymous survey regarding typical and ideal usage of time on FCR. Data analysis included general linear models and analysis of variance tests. RESULTS: Thirty rounding sessions involving 234 encounters of FCR over a 12-week period were analyzed. On average, teams spent 7 minutes in each patient room and approximately the same amount of time outside of the room. Attending physicians were the dominant medical speakers during rounds (30.8%), and nurses spoke the least (2%). When inside a patient room, there was no significant difference between the percentage of time that attending physicians spoke (25.6%) and that of families and patients (23.0%). The surveys revealed that the medical team consistently underestimated the percentage of time attending physicians talked and desired attending physicians to talk less. They also overestimated the time spent in the patient rooms, the time families talked, and nurse presence during rounds and desired an increase in each of these areas. CONCLUSIONS: The medical teams' perceptions of FCR do not reflect clinical observations. Medical teams believe and desire that attending physicians talk less and families and nurses talk more than observations reveal. PMID- 27282553 TI - A Family's Perspective on Family-Centered Rounds: Progress and Frustrations. PMID- 27282554 TI - The Family System and Depressive Symptoms during the College Years: Triangulation, Parental Differential Treatment, and Sibling Warmth as Predictors. AB - Guided by Bowen theory, we investigated the relationships between parent-child triangulation, parental differential treatment (PDT), sibling warmth, and individual depressive symptoms in a sample of 77 sibling dyads, aged 18-25 years, recruited through undergraduate classes at a U.S. public University. Results of the actor-partner interdependence models suggested that being triangulated into parental conflict was positively related to both siblings' perception of PDT; however, as one sibling felt triangulated, the other perceived reduced levels of PDT. For both siblings, the perception of higher levels of PDT was related to decreased sibling warmth and higher sibling warmth was associated with fewer depressive symptoms. The implications of these findings for research and the treatment of depression in the college-aged population are discussed. PMID- 27282555 TI - Respiratory cancer mortality and incidence in an updated cohort of Canadian nickel production workers. AB - Respiratory cancer mortality and incidence were examined in an updated cohort of >56,000 Canadian nickel mining and refining workers. There was little evidence to suggest increased lung cancer risk in workers who had no experience in high-risk sintering operations that were closed by 1972, apart from that which would be expected from probable increased smoking prevalence relative to the comparison population. There was no substantive evidence of increased laryngeal cancer risk in the cohort, nor was there evidence of increased pharyngeal cancer risk in nonsinter workers. Nasal cancer incidence was elevated in nonsinter workers, but excess risks appeared to be confined to those hired prior to 1960. These findings lead us to tentatively conclude that occupationally-related respiratory risks in workers hired over the past 45 years are either very low or nonexistent. PMID- 27282556 TI - Wider than Thought Phylogenetic Occurrence of Apicortin, A Characteristic Protein of Apicomplexan Parasites. AB - Apicomplexan parasites cause serious illnesses, including malaria, in humans and domestic animals. The presence of apicortins is predominantly characteristic of this phylum. All the apicomplexan species sequenced contain an apicortin which unites two conserved domains: DCX and partial p25alpha. This paper identifies novel apicortin orthologs in silico and corrects in several cases the erroneous sequences of hypothetical apicortin proteins of Cryptosporidium, Eimeria, and Theileria genera published in databases. Plasmodium apicortins, except from Plasmodium gallinaceum, differ significantly from the other apicomplexan apicortins. The feature of this ortholog suggests that only orthologs of Plasmodiums hosted by mammals altered significantly. The free-living Chromerida, Chromera velia, and Vitrella brassicaformis, contain three paralogs. Their apicomplexan-type and nonapicomplexan-type apicortins might be "outparalogs." The fungal ortholog, Rozella allomycis, found at protein level, and the algal Nitella mirabilis, found as Transcriptome Shotgun Assembly (TSA), are similar to the known Opisthokont (Trichoplax adhaerens, Spizellomyces punctatus) and Viridiplantae (Nicotiana tabacum) ones, since they do not contain the long, unstructured N-terminal part present in apicomplexan apicortins. A few eumetazoan animals possess apicortin-like (partial) sequences at TSA level, which may be either contaminations or the result of horizontal gene transfer; in some cases the contamination has been proved. PMID- 27282557 TI - Robustness of two-step acid hydrolysis procedure for composition analysis of poplar. AB - The NREL standard procedure for lignocellulosic biomass composition has two steps: primary hydrolysis in 72% wt sulfuric acid at 30 degrees C for 1h followed by secondary hydrolysis of the slurry in 4wt% acid at 121 degrees C for 1h. Although pointed out in the NREL procedure, the impact of particle size on composition has never been shown. In addition, the effects of primary hydrolysis time and separation of solids prior to secondary hydrolysis on composition have never been shown. Using poplar, it was found that particle sizes less than 0.250mm significantly lowered the glucan content and increased the Klason lignin but did not affect xylan, acetate, or acid soluble lignin contents. Composition was unaffected for primary hydrolysis time between 30 and 90min. Moreover, separating solids prior to secondary hydrolysis had negligible effect on composition suggesting that lignin and polysaccharides are completely separated in the primary hydrolysis stage. PMID- 27282558 TI - Site-Selective Tertiary Alkyl-Fluorine Bond Formation from alpha-Bromoamides Using a Copper/CsF Catalyst System. AB - A copper-catalyzed site-selective fluorination of alpha-bromoamides possessing multiple reaction sites, such as primary and secondary alkyl-Br bonds, using inexpensive CsF is reported. Tertiary alkyl-F bonds, which are very difficult to synthesize, can be formed by this fluorination reaction with the aid of an amide group. Control experiments revealed that in situ generated CuF2 is a key fluorinating reagent that reacts with the tertiary alkyl radicals generated by the reaction between an alpha-bromocarbonyl compound and a copper(I) salt. PMID- 27282559 TI - A Systematic Review and Meta-Synthesis of Patients' Experiences and Perceptions of Seeking and Using Benzodiazepines and Z-Drugs: Towards Safer Prescribing. AB - BACKGROUND: Benzodiazepines and Z-drugs are used to treat complaints like insomnia, anxiety and pain. These drugs are recommended for short-term use only, but many studies report long-term use, particularly in older people. OBJECTIVE: The aim of this study was to identify and synthesise qualitative studies exploring patients' experiences and perceptions of receiving benzodiazepines and Z-drugs, and through this identify factors which perpetuate use of these drugs, and strategies for achieving safer prescribing. METHODS: A systematic search of six databases for qualitative studies exploring patients' experiences and perceptions of primary care benzodiazepine and z-drug prescribing published between January 2000 and April 2014 in a European language, and conducted in Europe, the United States, Australia or New Zealand. Reference lists of included papers were also searched. Study quality was assessed using the Critical Appraisal Skills Programme qualitative checklist. Findings were synthesised using thematic synthesis. RESULTS: Nine papers were included and seven analytical themes were identified relating to patients' experiences and perceptions and, within that, strategies for safer prescribing of benzodiazepines and Z-drugs: (1) patients' negative perceptions of insomnia and its impact, (2) failed self-care strategies, (3) triggers to medical help-seeking, (4) attitudes towards treatment options and service provision, (5) varying patterns of use, (6) withdrawal, (7) reasons for initial or ongoing use. CONCLUSIONS: Inappropriate use and prescribing of benzodiazepines and Z-drugs is perpetuated by psychological dependence, absence of support and patients' denial/lack of knowledge of side effects. Education strategies, increased availability of alternatives, and targeted extended dialogue with patients could support safer prescribing. PMID- 27282560 TI - Neutrophil elastase enhances IL-12p40 production by lipopolysaccharide-stimulated macrophages via transactivation of the PAR-2/EGFR/TLR4 signaling pathway. AB - Proteinase-activated receptor 2 (PAR-2) and toll-like receptor 4 (TLR4) are involved in innate immune responses and signaling cross-talk between these receptor molecules has the potential to augment an ongoing inflammatory response. The aim of this study was to evaluate the possible cooperative influence of PAR-2 and TLR4 on IL-12p40 production by macrophages after stimulation with lipopolysaccharide (LPS). During culture, GM-CSF upregulated PAR-2 expression by macrophages in a time-dependent manner. Stimulation with LPS enhanced IL-12p40 production by macrophages in a concentration-dependent manner. While human neutrophil elastase (HNE) did not induce IL-12p40 production, pretreatment of macrophages with HNE synergistically increased the IL-12p40 protein level after LPS exposure. Silencing of TLR4 with small interfering RNA blunted the synergistic enhancement of IL-12p40 by HNE combined with LPS. Silencing of beta arrestin 2, p22phox, or ERK1/2 also inhibited an increase of IL-12p40. Interestingly, transfection of macrophages with small interfering RNA duplexes for DUOX-2, EGFR, TLR4, or TRAF6 significantly blunted the increase of IL-12p40 in response to treatment with HNE plus LPS. U73122 and Rottlerin also inhibited the increased production of IL-12p40. In conclusion, HNE is involved in transactivation of TLR4 through activation of DUOX-2/EGFR and synergistically enhances IL-12p40 production by macrophages stimulated with LPS. PMID- 27282561 TI - Persistent immune alterations and comorbidities in splenectomized patients with Gaucher disease. AB - Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the gene encoding acid-beta-glucosidase, resulting in functional disruptions in degradation of glycosphingolipids and lysosomal accumulation of the substrates. The most frequent clinical presentations of GD are thrombocytopenia, splenomegaly and bone pain. Prior to advent of enzyme replacement therapy, splenectomy was performed for complications of hypersplenism such as severe thrombocytopenia and transfusion dependency. Though there is evidence about worsening bone disease after splenectomy, there is no systematic study to assess its effects on the immune system in GD patients. In order to investigate the long-term immunological effects of splenectomy, we used flow cytometry to compare the immunophenotypes of GD patients who had undergone splenectomy (SGD) to those with intact spleen. The results show that SGD patients have significantly fewer CD27(+)/IgM(+) B-cells but more CD4(+)/CD45RO(+) and CD8(+)/CD45RO(+) T-cells. The most surprising finding was an almost complete absence of circulating dendritic cells in SGD patients. In addition, splenectomized subjects had comorbidities, the most common being monoclonal gammopathy of undetermined significance (MGUS). Taken together, these results highlight the persistence of multiple immune alterations and comorbidities coexisting in higher frequency in the SGD group and they are not affected by GD specific therapy. PMID- 27282562 TI - AMD3100 and G-CSF disrupt the cross-talk between leukemia cells and the endosteal niche and enhance their sensitivity to chemotherapeutic drugs in biomimetic polystyrene scaffolds. AB - BACKGROUND: The multidrug resistance of leukemia cells is closely related to the microenvironment. The present leukemia microenvironment models focus on two dimensional co-culture system in vitro which does not mimic the in vivo cell growth, while the 3D polystyrene (PS) scaffolds have the advantage. Stromal cell derived factor-1 may be involved in the shielding of endosteal niche from leukemia cells by binding to its receptor CXCR4, but the relationship between SDF 1/CXCR4 axis and leukemia cells is unclear. DESIGN AND METHODS: The experiments were built on the 3D PS scaffolds coated with osteoblasts. Stromal cells and MV4 11 cells were plated on the scaffolds. Then G-CSF, AMD3100 and cytarabine were added. Adhesive rate, SDF-1 level, migration state, apoptosis rate, and cell cycle of leukemia cells were observed after incubation at 24h and 48h. RESULTS: G CSF decreased the level of SDF-1 and inhibited the expression of CXCR4 and promoted stationary phase leukemia cells to enter the mitotic phase and enhanced the killing effect of chemotherapeutic drugs. AMD3100 disrupted the interaction between tumors and matrix, mobilized the leukemia cells to keep away from the protective microenvironment and strengthened the cytotoxic effect of Ara-C. The combination of G-CSF and AMD3100 had stronger effects on killing the leukemia cells induced by Ara-C. CONCLUSION: It demonstrates that AMD3100 and G-CSF may inhibit adhesion and migration abilities of leukemia cells with the bone marrow niche. Both of them inhibit the role of SDF-1/CXCR4 directly or indirectly. Thus inhibiting SDF-1/CXCR4 axis may be helpful to the treatment of refractory AML. PMID- 27282563 TI - The expression of Death Inducer-Obliterator (DIDO) variants in Myeloproliferative Neoplasms. AB - Chronic Myeloid Leukemia (CML), Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are Myeloproliferative Neoplasms (MPN) characterized by clonal myeloproliferation without cell maturation impairment. CML pathogenesis is associated with the Ph chromosome leading to BCR-ABL tyrosine kinase constitutive expression. The Ph negative MPN (PV, ET and PMF) are characterized by the mutation JAK2(V617F) of the JAK2 protein in the auto inhibitory JH2 domain, which is found in most PV patients and in approximately half of ET and PMF patients. Considerable effort is being made to understand the role of JAK2(V617F) at the MPN initiation and to clarify the pathogenesis and apoptosis resistance in CML, PV, ET and PMF patients. In the present investigation, we evaluated the Death Inducer-Obliterator (DIDO) (variants DIDO 1, 2 and 3) levels in CML, PV, ET and PMF patients. Our data reported the DIDO 1, 2 and 3 differential expressions in Myeloproliferative Neoplasms. PMID- 27282564 TI - Erythrocyte glutathione is a novel biomarker of Diamond-Blackfan anemia. AB - Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia with mutations in ribosomal protein (RP) genes. Elevated activity of erythrocyte adenosine deaminase (eADA) has been utilized as a biomarker of DBA. We examined erythrocyte reduced glutathione (GSH) as well as eADA in 22 patients in 18 DBA families, in whom RP gene mutations had been identified. Simultaneous evaluation of both eADA and GSH demonstrated that all examined DBA patients showed elevated values of either eADA or GSH, whereas presence of both eADA and GSH elevation was able to distinguish DBA patients from 34 normal controls and 14 unaffected members of the DBA families. Furthermore, a support vector machines analysis using both eADA and GSH levels yielded a formula to differentiate DBA from both normal controls and non-DBA family members. To confirm the usefulness of the formula, we analyzed additional 7 patients diagnosed by the clinical criteria. Although eADA showed within normal values in 3 patients, all of these patients were diagnosed as 'DBA' by use of the formula. Because extensive analysis of the RP genes failed to detect no causative mutation in approximately 40% of clinically diagnosed DBA patients, GSH may be useful an additional biomarker for diagnosis of DBA. PMID- 27282565 TI - Development of anti-velaglucerase alfa antibodies in clinical trial-treated patients with Gaucher disease. AB - Anti-drug antibodies may develop with biological therapies, possibly leading to a reduction of treatment efficacy and to allergic and other adverse reactions. Patients with Gaucher disease were tested for anti-drug antibodies every 6 or 12weeks in clinical studies of velaglucerase alfa enzyme replacement therapy, as part of a range of safety endpoints. In 10 studies between April 2004 and March 2015, 289 patients aged 2-84years (median 43years) were assessed for the development of anti-velaglucerase alfa antibodies. Sixty-four patients were treatment-naive at baseline and 225 patients were switched to velaglucerase alfa from imiglucerase treatment. They received velaglucerase alfa treatment for a median of 36.4weeks (interquartile range 26.4-155.4weeks). Four patients (1.4%) became positive for anti-velaglucerase alfa IgG antibodies, two of whom had antibodies that were neutralizing in vitro, but there were no apparent changes in patients' platelet counts, hemoglobin levels or levels of CCL18 and chitotriosidase, suggestive of clinical deterioration after anti-velaglucerase alfa antibodies were detected, and no infusion-related adverse events were reported. Less than 2% of patients exposed to velaglucerase alfa tested positive for antibodies and there was no apparent correlation between anti-velaglucerase alfa antibodies and adverse events or pharmacodynamic or clinical responses. PMID- 27282566 TI - Erytrocyte-related phenotypes and genetic susceptibility to thrombosis. PMID- 27282567 TI - Variants of ZBTB7A (LRF) and its beta-globin gene cluster binding motifs in sickle cell anemia. PMID- 27282568 TI - Cytogenetic abnormalities and genomic copy number variations in EPO (7q22) and SEC-61(7p11) genes in primary myelodysplastic syndromes. AB - Myelodysplastic syndromes (MDSs) are heterogeneous clonal haematopoeitic stem cell disorders characterized by ineffective haematopoeisis, cytopenias and risk of progression to AML. We studied 150 MDS patients for cytogenetic aberrations and 60 patients with normal karyotype and 40 patients harboring cytogenetic abnormalities for copy number variations (CNVs). Cytogenetic abnormalities were detected in 46% of patients with a majority of patients harboring abnormalities of chromosome 7 and del (20q) at frequencies of 16% and 12% respectively. We explored the potential of quantitative multiplex PCR assay of short fluorescent fragments (QMPSF) to identify CNVs and correlated the findings with cytogenetic data and disease prognosis. CNVs (n=31) were detected in 28.3% of karyotypically normal and 23% patients with abnormal karyotype. Genetic losses or deletions (n=26) were more frequent than duplications (n=5). EPO (7q22) and SEC-61(7p11) emerged as new candidate genes susceptible to genetic losses with 57.7% deletions identified in regions on chromosome 7. The CNVs correlated with International Prognostic Scoring System (IPSS) intermediate disease risk group. Our integrative cytogenetic and copy number variation study suggests that abnormalities of chromosome 7 are predominant in Indian population and that they may play a secondary role in disease progression and should be evaluated further for asserting their clinical significance and influence on disease prognosis. PMID- 27282569 TI - EphB4-VAV1 signaling pathway is associated with imatinib resistance in chronic myeloid leukemia cells. AB - Imatinib (IM) resistant Chronic Myeloid Leukemia (CML) is an important issue to be addressed while treating CML patients. The present study analyzes the role of EphB4-VAV1 signaling in IM-resistant CML. EphB4 and VAV1 were overexpressed in IM resistant CML patients and K562-R cell line (K562-R). Then, we established stable under-expressing EphB4 cell line K562-R-EphB4-sh. VAV1 was down-regulated in K562 R-EphB4-sh cells. K562-R-EphB4-sh cells gained re-sensitivity to IM and K562-R cells showed mild IM resistance. However, EphB4 was no changed when the VAV1 was down-regulated. EphB4 and VAV1 were overexpressed in IM-resistant CML, VAV1might be the downstream moleculars of EphB4. These results suggest a potential role of EphB4-VAV1 signaling as therapeutic target of IM-resistant CML. PMID- 27282570 TI - Recombinant human erythropoietin-induced erythropoiesis regulates hepcidin expression over iron status in the rat. AB - The crosstalk between several factors controlling hepcidin synthesis is poorly clarified for different physiological and pathological conditions. Our aim was to study the impact of increasing recombinant human erythropoietin (rHuEPO) doses on erythropoiesis, iron metabolism and hepcidin, using a rat model. Male Wistar rats were divided in 5 groups: control (vehicle) and rHuEPO-treated groups (100, 200, 400 and 600IU/kgbody weight/week), 3 times per week, during 3weeks. Hematological and iron data were evaluated. The expression of several genes involved in iron metabolism was analyzed by qPCR. Liver hepcidin protein was evaluated by Western Blot. The rHuEPO treatment induced erythropoiesis and increased transferrin saturation (TSAT) in a dose dependent manner. Tf receptor 2 (TfR2), hemojuvelin (HJV) and bone morphogenetic protein 6 (BMP6) were up-regulated in rHuEPO200 group. Matriptase-2 was down-regulated in rHuEPO200 group, and up-regulated in the other rHuEPO-treated groups. Hepcidin synthesis was increased in rHuEPO200 group, and repressed in the rHuEPO400 and rHuEPO600 groups. Our study showed that when a high erythropoietic stimulus occurs, hepcidin synthesis is mainly regulated by TSAT; however, when the erythropoiesis rate reaches a specific threshold, extramedullary hematopoiesis is triggered, and the control of hepcidin synthesis is switched to matriptase-2, thus inhibiting hepcidin synthesis. PMID- 27282571 TI - Molecular characterization of six new cases of red blood cell hexokinase deficiency yields four novel mutations in HK1. AB - Hexokinase (HK) is a key enzyme of glycolysis, the only metabolic pathway able to provide the red blood cell with ATP. HK deficiency is a very rare hereditary disorder with severe chronic nonspherocytic hemolytic anemia (HNSHA) as a major clinical feature. To date, only 24 patients with HK deficiency have been identified. Here, we report the molecular analysis of six new cases of HK deficiency. A total of six different mutations were detected in HK1, four of them described here for the first time: c.2599C>T p.(His867Tyr), c.1799C>T p.(Thr600Met), c.873-2A>G and c.493-1G>A. The pathogenic nature of the identified missense mutations was confirmed by biochemical and 3-dimensional structural analysis. The effects of the novel splice site mutation c.873-2A>G were studied at the level of pre-mRNA processing, and confirmed at the protein level. All together, these results provide a better insight into the pathogenesis of this rare red cell disorder, and contribute to a better understanding of the genotype phenotype correlation in HK deficiency. PMID- 27282572 TI - Cholinergic activation enhances retinoic acid-induced differentiation in the human NB-4 acute promyelocytic leukemia cell line. AB - The non-neuronal cholinergic system (NNCS) has been shown to play a role in regulating hematopoietic differentiation. We determined the expression of cholinergic components in leukemic cell lines by Western blotting and in normal leukocyte subsets by flow cytometry and found a heterogeneous expression of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), choline transporter (CHT), M3 muscarinic acetylcholine receptor (M3-mAChR) and alpha7 nicotinic acetylcholine receptor (alpha7-nAChR). We then evaluated NNCS role in differentiation of human NB-4 acute promyelocytic leukemia cell line and discovered a dramatic induction of M3-mAChR after all-trans retinoic acid (ATRA) treatment (p<0.0001). Adding carbachol which is a cholinergic agonist to the ATRA treatment resulted in an increase of a granulocytic differentiation marker (CD11b) as compared with ATRA treatment alone (p<0.05), indicating that cholinergic activation enhanced ATRA in inducing NB-4 maturation. The combination of carbachol and ATRA treatment for 72h also resulted in decreased viability and increased cleaved caspase-3 expression when compared with ATRA treatment alone (p<0.05). However, this combination did not cause poly (ADP-ribose) polymerase (PARP) cleavage. Overall, we have shown that NB-4 cells expressed M3-mAChR in a differentiation-dependent manner and cholinergic stimulation induced maturation and death of ATRA-induced differentiated NB-4 cells. PMID- 27282573 TI - Nine known and five novel mutations in the erythroid transcription factor KLF1 gene and phenotypic expression of fetal hemoglobin in hemoglobin E disorder. AB - Hemoglobin E is the most common Hb variant found in South East Asia. Variation of Hb F expression in Hb E syndrome is associated with several genetic modifiers. We report several single nucleotide polymorphisms (SNPs), including nine known and five novel mutations of the Kruppel-like factor 1 (KLF1; an erythroid specific transcription factor) gene and determine their associations with phenotypic expression of Hb F in Hb E disorders. KLF1 mutations were examined using high resolution melting (HRM) assay and DNA sequencing in 575 homozygous Hb E, 278 heterozygous Hb E and 100 normal subjects. Fourteen mutations were mostly observed in subjects with elevated Hb F, including nine known mutations (G176AfsX179, T334R, R238H, -154 (C>T), A298P, S270W, R301H, -148 (G>A) and G335R and five novel mutations (Q217X, Q223X, Y290_S293del, K307N, and M358I). None of them, but the -148 (G>A), were observed in normal controls to have Hb F <1%. Combined KLF1 mutations with other SNPs including (G)gamma-XmnI, BCL11A and HBS1L MYB were associated with higher Hb F levels. KLF1 is therefore an important genetic factor associated with increased Hb F and in combination with other modifying factors could explain the phenotypic variation of Hb F expression in this common hemoglobinopathy. PMID- 27282574 TI - Flow-cytometry-based evaluation of peripheral blood lymphocytes in prognostication of newly diagnosed DLBCL patients. AB - AIMS: We aimed to analyse whether quantitative assessment of peripheral blood lymphocyte CD19(+)CD20(+)CD22(+)CD79a(+) B cells, CD3(+)CD4(+)CD5(+)CD8(+) T cells and CD4(+)CD25(+++)Foxp3high Treg can improve prognostication in DLBCL patients. METHODS: The absolute count of lymphocytes, B-cells, T-cells and Treg cells as well as the percentage of apoptotic cells were assessed by means of flow cytometry in all studied subjects. RESULTS: Significantly lower level of ALC and the percentage of apoptotic cells have been observed exclusively in DLBCL patients with HR. We also showed, that in comparison with LR, in HR and MR groups, there is a significant decrease in the absolute number of T-cells and Tregs. The applied treatment does no normalize the number of B-cells, Tregs and apoptotic cells only in the case of HR patients. CONCLUSIONS: Lymphopenia, the decreased absolute number of T cells, Tregs, and a percentage of apoptotic cells, correlates with clinical staging in DLBCL patients. The increased number of B cells and the decreased level of Tregs and apoptotic cells after treatment might predict a poor clinical outcome in patients treated with RCHOP. Thereby, flow cytometry-based evaluation of peripheral blood lymphocytes may be useful in prognostication of newly diagnosed DLBCL patients. PMID- 27282575 TI - Carbamazepine-induced thrombocytopenic purpura in a child: Insights from a genomic analysis. PMID- 27282577 TI - Biomedical science paper authorship: A modest proposal. PMID- 27282576 TI - Assessment of serum bioactive hepcidin-25, soluble transferrin receptor and their ratio in predialysis patients: Correlation with the response to intravenous ferric carboxymaltose. AB - BACKGROUND: No reliable biomarker exists to predict responsiveness to intravenous (IV) iron (Fe) in iron deficient patients with CKD. We aimed to investigate the clinical value of bioactive Hepcidin-25 and soluble Transferrin Receptor (sTfR) levels in predialysis patients. PATIENTS AND METHODS: In this prospective study 78 stable stage III-IV CKD predialysis patients with (responders) (40 patients) and without (non-responders) (38 patients) adequate erythropoiesis after IV administration of ferric-carboxymaltose (FCM). Patients were divided in two groups according to their response to IV administration of ferric-carboxymaltose (FCM). Along with measurements of common hematologic and blood chemistry parameters, determinations of sTfR and bioactive Hepcidin-25 were performed. RESULTS: Hepcidin-25 levels were lower in the responders (p=0.025), while sTfR and sTfR/Hepcidin-25 ratio were higher (p<0.01 and p=0.002 respectively). Diagnostic efficacy indicated cut off point of 1.49 for Hepcidin-25 had sensitivity 84% and specificity 48%, while cut off point of 1.21 for sTfR/Hepcidin-25 ratio had sensitivity 82% and specificity 52% to predict correctly response to iron supplementation therapy. Furthermore, log sTfR/Hepcidin-25 correlated negatively with hs-CRP (p=0.005) and IL-6 (p<0.04) in non-responders, while such correlations were not found in responders (p>0.05). CONCLUSIONS: These results suggest that lower Hepcidin-25, as well as higher sTfR and sTfR/Hepcidin-25 ratio were significant predictors of favorable hemoglobin response within a month after IV administration of FCM in patients with CKD. Further experiments and clinical studies in other groups of patients are needed to better elucidate the role of Hepcidin-25 and sTfR/Hepcidin-25 ratio as predictors of response to intravenous iron administration. PMID- 27282578 TI - APOBEC3G has the ability to programme T cell plasticity. AB - Recently Apolipoprotein B mRNA editing enzyme, Catalytic Polypeptide-like 3G (APOBEC3G) biology has assumed importance because of its role in oncogenesis. In this context, the present study was addressed to understand the immune-modulatory role of APOBEC3G through its effect upon the T-cell plasticity phenomenon. Such an attempt revealed that APOBEC3G has the inherent capacity to regulate genes coding for STAT3, NF-kappaB, CCL5, IL-6, IL-4, IFN-gamma, IL-10 and IL-17 coupled with downregulation of Treg cells within human peripheral blood mononuclear cells (PBMCs) without any noticeable influence upon CD4(+) and CD8(+) cell number. On the basis of these findings, we propose that APOBEC3G has the ability to induce T cell plasticity and modulate immune response. PMID- 27282579 TI - Significance of CD34/CD123 expression in detection of minimal residual disease in B-ACUTE lymphoblastic leukemia in children. AB - BACKGROUND: MRD is seen as the major cause of disease relapse. So, it gives important feedback about conventional treatment success and helps in selecting therapeutic alternatives. We aimed to compare the expression of CD34/CD123 on normal B-cell precursors in bone marrow ("hematogones") and on leukemic blasts in B-acute lymphoblastic leukemias (B-ALL) pediatric cases by flowcytometric analysis. Our study conducted on 20 children as a control and 30 B-ALL children cases at diagnosis and after 28days of induction therapy. We found that the less mature hematogones (dim CD45+) that express CD34 lack CD123 expression, whereas the more mature hematogones (moderate CD45+) lack CD34 but always express CD123. In contrast with this discordant pattern of CD34 and CD123 expression in hematogones, blasts in 24 of 30 cases (80%) of B-ALL showed concordant expression pattern of the 2 antigens: 63% (19 of 30) cases expressed both antigens, whereas 17% (5 of 30) expressed neither. Our study concluded that these distinct patterns of CD34/CD123 expression on hematogones (discordant) and B-ALL blasts (concordant) are useful in differentiating small populations of residual blasts from hematogones after induction therapy to detect MRD. PMID- 27282580 TI - LDH and age are associated with hemolysis-endothelial dysfunction in HbSC patients. PMID- 27282581 TI - Transgenic sickle cell trait mice do not exhibit abnormal thermoregulatory and stress responses to heat shock exposure. AB - There remains controversy over whether individuals with sickle cell trait (SCT) are vulnerable to health risks during physical activity in high temperatures. We examined thermoregulatory and stress-related responses to heat exposure in SCT and wild-type (WT) mice. No significant differences in core temperature (Tc) were observed between SCT and WT mice during heat exposure. There was no correlation between peak Tc during heat exposure and levels of hemoglobin S in SCT mice. Basal levels of circulating inflammatory and stress-related markers were not significantly different between SCT and WT mice. Although heat exposure caused significant increases in plasma interleukins 1beta and 6, and 8-isoprostane in SCT and WT mice, no differences were found between SCT and WT mice with similar thermal response profiles during heat exposure. SCT mice had significantly higher expression of heat shock protein 72 in heart, liver and gastrocnemius muscle than WT mice under control and post-heat conditions. In conclusion, there is neither thermoregulatory dysfunction nor abnormal stress-related response in SCT mice exposed to moderate heat. The hemoglobin variant in mice is associated with altered tissue stress protein homeostasis. PMID- 27282582 TI - TP53 codon 72 polymorphism predicts chronic myeloid leukemia susceptibility and treatment outcome. AB - BCR-ABL1 gene is a key molecular marker of chronic myeloid leukemia (CML), but it is still unclear which molecular factors may influence CML risk or lead to variable responses to tyrosine kinase inhibitors (TKIs). The aim of this study was to investigate the impact of TP53 c.213 G>C(Arg72Pro; rs1042522) polymorphism on CML risk and its correlation with clinical outcome. Peripheral blood samples from 141 treated CML patients and 141 sex- and age-matched healthy individuals were genotyped by PCR-RFLP. Standard genetic models for disease penetrance were evaluated by logistic regression analysis and Kaplan-Meier method was performed to estimate survival curves. Our study suggests that TP53 c.213 G>C polymorphism may be involved in CML development considering a recessive model (p=0.01; OR: 0.19; CI: 0.06-0.68). In addition, a non-homogenous distribution was found for this polymorphism in males and patients youngers than 50years (p=0.02). According to clinical response, TP53-GG genotype was associated with higher levels of BCR ABL1 transcripts (p=0.04) and shorter event free survival (p=0.04). Moreover, a trend toward significance was found for failure free survival (p=0.06) and time to imatinib failure (p=0.08). In conclusion, our data suggest that a;TP53 c.213 G>C may be a potential biomarker of CML susceptibility and clinical outcome. PMID- 27282583 TI - Red blood cell-derived microparticles: An overview. AB - The red blood cell (RBC) is historically the original parent cell of microparticles (MPs). In this overview, we describe the discovery and the early history of red cell-derived microparticles (RMPs) and present an overview of the evolution of RMP. We report the formation, characteristics, effects of RMP and factors which may affect RMP evaluation. The review examines RMP derived from both normal and pathologic RBC. The pathologic RBC studies include sickle cell anemia (SCA), sickle cell trait (STr), thalassemia intermedia (TI), hereditary spherocytosis (HS), hereditary elliptocytosis (HE), hereditary stomatocytosis (HSt) and glucose-6-phosphate dehydrogenase deficiency (G6PD). PMID- 27282584 TI - Online model checking for monitoring surrogate-based respiratory motion tracking in radiation therapy. AB - OBJECTIVE: Correlation between internal and external motion is critical for respiratory motion compensation in radiosurgery. Artifacts like coughing, sneezing or yawning or changes in the breathing pattern can lead to misalignment between beam and tumor and need to be detected to interrupt the treatment. We propose online model checking (OMC), a model-based verification approach from the field of formal methods, to verify that the breathing motion is regular and the correlation holds. We demonstrate that OMC may be more suitable for artifact detection than the prediction error. MATERIALS AND METHODS: We established a sinusoidal model to apply OMC to the verification of respiratory motion. The method was parameterized to detect deviations from typical breathing motion. We analyzed the performance on synthetic data and on clinical episodes showing large correlation error. In comparison, we considered the prediction error of different state-of-the-art methods based on least mean squares (LMS; normalized LMS, nLMS; wavelet-based multiscale autoregression, wLMS), recursive least squares (RLSpred) and support vector regression (SVRpred). RESULTS: On synthetic data, OMC outperformed wLMS by at least 30 % and SVRpred by at least 141 %, detecting 70 % of transitions. No artifacts were detected by nLMS and RLSpred. On patient data, OMC detected 23-49 % of the episodes correctly, outperforming nLMS, wLMS, RLSpred and SVRpred by up to 544, 491, 408 and 258 %, respectively. On selected episodes, OMC detected up to 94 % of all events. CONCLUSION: OMC is able to detect changes in breathing as well as artifacts which previously would have gone undetected, outperforming prediction error-based detection. Synthetic data analysis supports the assumption that prediction is very insensitive to specific changes in breathing. We suggest using OMC as an additional safety measure ensuring reliable and fast stopping of irradiation. PMID- 27282585 TI - Psychodermatology: Basics Concepts. AB - Psychodermatology is a relatively new field of medicine. It encompasses the interaction of mind and skin. The role of psychoneuroimmunology in the causation of psychocutaneous disorders and psychosocial aspects of skin disease have gained momentum lately. The treatment of psychodermatological disorders focus on improving function, reducing physical distress, diagnosing and treating depression and anxiety associated with skin disease, managing social isolation and improving self esteem of the patient. Both pharmacological and psychological interventions are used in treating psychocutaneous disorders. The interest in Psychodermatology around the world is increasing and there are several organizations holding their regular meetings. PMID- 27282586 TI - Managing Breast Cancer: Echoes from Patients in Lagos, Nigeria. AB - Breast cancer is ranked second as the cause of cancer death among women. Of importance to the management of breast cancer is the interaction processes between the patients and their professional caregivers or healthcare providers. Against this background, this study explores the experiences of Nigerian women as breast cancer patients and their interaction with their caregivers in the management of their condition. The study was cross-sectional in design. Twenty diagnosed breast cancer patients participated in the study and were purposively selected using convenience and snow balling sampling technique. Patients affirmed that they were initially afraid when diagnosed but overcame their fear based on caregivers' supports. Physical interactions and the use of mobile phones were common means of communication while the fear of death and financial burden of the disease were of major concerns to the patients. The majority of the patients were satisfied with the quality of care and treatment received in the private hospitals as they were encouraged and supported. It was discovered that professional caregivers are germane to patients' survival from shock and adequate information on how to manage their condition and live a normal life. PMID- 27282587 TI - Pulsed dye laser in the treatment of psoriatic nails: a controlled study. PMID- 27282588 TI - Koebner's Phenomenon in Childhood Henoch-Schonlein Purpura: A Report of Two Cases. AB - Koebner's phenomenon occurs rarely in connection with Henoch-Schonlein purpura (HSP). We report two children with HSP who developed Koebner's phenomenon on the second day after the onset of rash. The first was an 11-year-old girl with rheumatic heart disease who presented with abdominal pain for 1 month and subsequently developed rash and nephritis. The second patient was a 7-year-old girl who presented with rash and polyarthritis. To the best of our knowledge, Koebner's phenomenon in childhood HSP has not been reported. PMID- 27282589 TI - Structure-activity relationship studies of benzyl-, phenethyl-, and pyridyl substituted tetrahydroacridin-9-amines as multitargeting agents to treat Alzheimer's disease. AB - A library of substituted tetrahydroacridin-9-amine derivatives were designed, synthesized, and evaluated as dual cholinesterase and amyloid aggregation inhibitors. Compound 8e (N-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydroacridin-9 amine) was identified as a potent inhibitor of butyrylcholinesterase (BuChE IC50 = 20 nm; AChE IC50 = 2.2 MUm) and was able to inhibit amyloid aggregation (40% inhibition at 25 MUm). Compounds 9e (6-chloro-N-(3,4-dimethoxybenzyl)-1,2,3,4 tetrahydroacridin-9-amine, AChE IC50 = 0.8 MUm; BuChE IC50 = 1.4 MUm; Abeta aggregation inhibition = 75.7% inhibition at 25 MUm) and 11b (6-chloro-N-(3,4 dimethoxyphenethyl)-1,2,3,4-tetrahydroacridin-9-amine, AChE IC50 = 0.6 MUm; BuChE IC50 = 1.9 MUm; Abeta-aggregation inhibition = 85.9% inhibition at 25 MUm) were identified as the best compounds with dual cholinesterase and amyloid aggregation inhibition. The picolylamine-substituted compound 12c (6-chloro-N (pyridin-2-ylmethyl)-1,2,3,4-tetrahydroacridin-9-amine) was the most potent AChE inhibitor (IC50 = 90 nm). These investigations demonstrate the utility of 3,4 dimethoxyphenyl substituent as a novel pharmacophore possessing dual cholinesterase inhibition and anti-Abeta-aggregation properties that can be used in the design and development of small molecules with multitargeting ability to treat Alzheimer's disease. PMID- 27282590 TI - SERP: a growing society and with an European horizon. PMID- 27282591 TI - Improving analytical methods for protein-protein interaction through implementation of chemically inducible dimerization. AB - When investigating interactions between two proteins with complementary reporter tags in yeast two-hybrid or split GFP assays, it remains troublesome to discriminate true- from false-negative results and challenging to compare the level of interaction across experiments. This leads to decreased sensitivity and renders analysis of weak or transient interactions difficult to perform. In this work, we describe the development of reporters that can be chemically induced to dimerize independently of the investigated interactions and thus alleviate these issues. We incorporated our reporters into the widely used split ubiquitin-, bimolecular fluorescence complementation (BiFC)- and Forster resonance energy transfer (FRET)- based methods and investigated different protein-protein interactions in yeast and plants. We demonstrate the functionality of this concept by the analysis of weakly interacting proteins from specialized metabolism in the model plant Arabidopsis thaliana. Our results illustrate that chemically induced dimerization can function as a built-in control for split based systems that is easily implemented and allows for direct evaluation of functionality. PMID- 27282592 TI - Influence of Catastrophizing and Personality Traits on Recalled Ratings of Acute Pain Experience in Healthy Young Adults. AB - Objective: To investigate whether pain catastrophizing and personality traits bias recalled ratings of acute pain in an experimental tonic pain model. Subjects and Setting: Fifty-six undergraduates (14 males) recruited from the University of Peradeniya (mean age 21.7 +/- 0.8 SD years). Design and Methods: Participants completed the Pain Catastrophizing Scale and the Eysenck Personality Questionnaire. They were subjected to two cold pressor tests (dominant and non dominant hands) and pain threshold, maximum pain intensity, and pain tolerance were recorded. One-week later, the maximum pain intensities of both hands were recalled and percentage distortions in recalling were calculated. Based on a 180 s cutoff, two participants were considered pain-insensitive during the test and were excluded from the analysis. Results: The maximum pain intensity was recalled with a moderate accuracy (Intraclass Correlation Coefficients = 0.68 for dominant and 0.59 for non-dominant hands). Hierarchical multiple regression analyses revealed that maximum pain intensity ( P < 0.001) and pain catastrophizing ( P < 0.001) contributed significantly to recalled pain intensity, and only pain catastrophizing contributed significantly ( P < 0.001) to percentage distortion in recalling with positive beta-coefficients. Participants who consistently overrated pain for both hands in recalling scored significantly higher on catastrophizing ( P < 0.001). Conclusion: This study demonstrated that memory for painful events in healthy subjects was reasonably accurate over a period of 1 week. Pain catastrophizing biased pain recall, whereas among personality traits only neuroticism exhibited a weak positive association with the recalled ratings. PMID- 27282594 TI - Extra Corporeal Shock Wave Therapy Versus Local Corticosteroid Injection in the Treatment of Chronic Plantar Fasciitis, a Single Blinded Randomized Clinical Trial. AB - OBJECTIVES: Plantar fasciitis is a self-limiting condition, but can be painful and disabling. Among the different treatments which exist, corticosteroid injections are effective and popular. Extracorporeal shock wave therapy (ESWT) is another treatment modality used for resistant conditions. In this study, the authors evaluated the efficacy of radial ESWT versus corticosteroid injections in the treatment of chronic plantar fasciitis. DESIGN: Randomized clinical trial. SETTING: Physical medicine and rehabilitation research center in a university hospital. SUBJECTS: Forty patients with plantar fasciitis who did not respond to conservative treatment. METHODS: Patients were allocated to radial ESWT with 2000 shock waves/session of 0.2 mJ/mm(2) (n = 20) or local methylprednisolone injections (n = 20). Pain in the morning and during the day based on a visual analog scale (VAS), functional abilities using the foot function index (FFI), and satisfaction were evaluated before treatment and at 4 and 8 weeks after treatment. RESULTS: Patients (average age: 42.1+/- 8.20) received five sessions of ESWT or single steroid injection. Changes in the VAS in morning and during the day and the FFI throughout the study period were significant in both groups (P < 0.001). ESWT group had a higher reduction in VAS in morning and better function in FFI, but these changes were insignificant statistically [FFI decreased to 19.65 +/- 21.26 points (67.4% improvement) in ESWT vs 31.50 +/- 20.53 points (47.7%) in injection group at week 8, P = 0.072)]. Good or excellent results in the opinions of patients were achieved in 55% of ESWT and 30% of corticosteroid injection groups (P = 0.11). CONCLUSION: Both interventions caused improvement in pain and functional ability 2 months after treatment. Although inter-group differences were not significant, the FFI was improved more with ESWT and patients were more satisfied with ESWT, thus shockwave therapy seems a safe alternative for management of chronic plantar fasciitis. PMID- 27282595 TI - Using self-organizing maps to infill missing data in hydro-meteorological time series from the Logone catchment, Lake Chad basin. AB - Hydro-meteorological data is an important asset that can enhance management of water resources. But existing data often contains gaps, leading to uncertainties and so compromising their use. Although many methods exist for infilling data gaps in hydro-meteorological time series, many of these methods require inputs from neighbouring stations, which are often not available, while other methods are computationally demanding. Computing techniques such as artificial intelligence can be used to address this challenge. Self-organizing maps (SOMs), which are a type of artificial neural network, were used for infilling gaps in a hydro-meteorological time series in a Sudano-Sahel catchment. The coefficients of determination obtained were all above 0.75 and 0.65 while the average topographic error was 0.008 and 0.02 for rainfall and river discharge time series, respectively. These results further indicate that SOMs are a robust and efficient method for infilling missing gaps in hydro-meteorological time series. PMID- 27282596 TI - The Pharmacodynamics of Switching Between P2Y12 Receptor Antagonists. PMID- 27282598 TI - A Simple, Effective, and Durable Treatment Choice for Left Main Coronary Artery Disease: Stents or Surgery? PMID- 27282597 TI - Coronary Artery Bypass Graft Surgery and Percutaneous Coronary Interventions in Patients With Unprotected Left Main Coronary Artery Disease. AB - OBJECTIVES: This study sought to investigate long-term clinical outcomes following coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in patients with unprotected left main disease (ULMD). BACKGROUND: PCI has been increasingly used as an alternative mode of revascularization for ULMD. However, there are limited data comparing clinical outcomes between CABG surgery and PCI. METHODS: Between 2004 and 2010, 4,046 consecutive patients with ULMD were treated with either CABG surgery (n = 2,604) or PCI (n = 1,442) with drug-eluting stents. The primary outcome was 3-year all cause mortality and the secondary outcome was the composite of death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: The unadjusted 3-year all cause mortality was higher in the PCI group as compared with the CABG group (3.8% vs. 2.5%; log-rank p = 0.03), although there was no significant difference in the composite outcome (7.5% vs. 9.4%; log-rank p = 0.07). After adjustment for differences in baseline risk factors, PCI was associated with significantly higher risk of all-cause mortality (hazard ratio [HR]: 1.71; 95% confidence interval [CI]: 1.32 to 2.21; p < 0.001) but similar risk of the composite outcome (HR: 0.94; 95% CI: 0.82 to 1.09; p = 0.43). These differences were not statistically significant among patients with low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (<=32) or diabetes; however, PCI was associated with an increased risk among those with high SYNTAX score (>32), with HRs of 3.10 (95% CI: 1.84 to 5.22; p < 0.001) for all-cause mortality and 1.82 (95% CI: 1.36 to 2.45; p < 0.001) for the composite outcome. CABG was associated with lower risk of repeat revascularization but higher risk of stroke in each clinically relevant subgroup. CONCLUSIONS: In this single-center observational study among patients with ULMD, CABG was associated with improved long-term outcomes, especially in patients with more complex disease. PMID- 27282599 TI - Coronary Stent Fracture: A New Form of Patient-Prosthesis Mismatch? PMID- 27282600 TI - Transseptal Instead of Transapical Valve Implantation: Making Mitral Great Again? PMID- 27282602 TI - Leaving Nothing Behind: Bioresorbable Vascular Scaffolds for Femoropopliteal Disease. PMID- 27282603 TI - Simultaneous Coronary and Pulmonary Angiography to Diagnose Critical Left Main Coronary Artery Stenosis Secondary to Dilated Pulmonary Artery. PMID- 27282601 TI - Bioresorbable Everolimus-Eluting Vascular Scaffold for Patients With Peripheral Artery Disease (ESPRIT I): 2-Year Clinical and Imaging Results. AB - OBJECTIVES: This is the first-in-human study of a drug-eluting bioresorbable vascular scaffold (BVS) for treatment of peripheral artery disease (PAD) involving the external iliac artery (EIA) and superficial femoral artery (SFA). BACKGROUND: Drug-eluting BVS has shown promise in coronary arteries. METHODS: The ESPRIT BVS system is a device-drug combination consisting of an everolimus eluting poly-l-lactide scaffold. Safety and performance were evaluated in 35 subjects with symptomatic claudication. RESULTS: Lesions were located in the SFA (88.6%) and EIA (11.4%). Mean lesion length was 35.7 +/- 16.0 mm. The study device was successfully deployed in 100% of cases, without recoil. Procedure related minor complications were observed in 3 patients (groin hematoma, dissection). Within 2 years there was 1 unrelated death, but no patients in this cohort had an amputation. At 1 and 2 years, the binary restenosis rates were 12.1% and 16.1%, respectively, and target lesion revascularization was performed in 3 of 34 patients (8.8%) and 4 of 32 patients (11.8%), respectively. The ankle brachial index 0.75 +/- 0.14 improved from pre-procedure to 0.96 +/- 0.16 at 2 years' follow-up. At 2 years, 71.0% of the patients were Rutherford-Becker 0, and 93.5% achieved a maximum walking distance of 1,500 feet. CONCLUSIONS: The safety of the ESPRIT BVS was demonstrated with no procedure or device-related deaths or amputations within 2 years. The low occurrence of revascularizations was consistent with duplex-ultrasonography showing sustained patency at 2-years. (A Clinical Evaluation of the Abbott Vascular ESPRIT BVS [Bioresorbable Vascular Scaffold] System [ESPRIT I]; NCT01468974). PMID- 27282604 TI - The MANTA Vascular Closure Device: A Novel Device for Large-Bore Vessel Closure. PMID- 27282605 TI - Fully Percutaneous Technique for Transaxillary Implantation of the Impella CP. PMID- 27282606 TI - Does Chronic Total Occlusion Percutaneous Coronary Intervention Improve Survival: A Never-Ending Debate. PMID- 27282607 TI - Reply: Does Chronic Total Occlusion Percutaneous Coronary Intervention Improve Survival: A Never-Ending Debate. PMID- 27282608 TI - Universal Health Care: Is it Impossible? PMID- 27282609 TI - Dual Anomalous Origins of the Thyrocervical Trunk and Left Internal Mammary Artery. PMID- 27282610 TI - A Novel Push-Fold Method for Removing Side Branch-Jailed Stent Struts Under 3D Optical Coherence Tomography Guidance. PMID- 27282611 TI - Association of TNFalpha-308, IFNgamma+874, and IL10-1082 gene polymorphisms and the risk of non-small cell lung cancer in the population of the South Indian state of Telangana. AB - BACKGROUND: Cytokine-mediated inflammation is important in the pathogenesis of non-small cell lung cancer (NSCLC). Genetic polymorphisms in cytokine genes and their association with lung cancer in the Indian population have not been reported. METHODS: For the first time, we analyzed genetic polymorphisms of TNFalpha -308, IFNgamma +874, and IL10 -1082 genes in 246 NSCLC patients and 250 healthy controls in the South Indian population from Telangana using ARMS PCR. RESULTS: IFNgamma+874 A/T and IL10-1082 G/G gene polymorphisms were found to be significantly associated with NSCLC with 1.56- and 1.68-fold disease risk, respectively. There was no association between the risk of NSCLC and TNFalpha-308 polymorphism. Gene polymorphisms stratified according to smoking revealed that IFNgamma+874 A/T polymorphisms in smokers increased the disease risk by 2.91 fold. IL10-1082 G/G polymorphisms showed 2-fold increased risk among patients who were smokers when compared to the controls. However, there was no association between TNFalpha-308, IFNgamma+874, and IL10-1082 gene polymorphism and the stage of the NSCLC patients. The overall risk associated with the combination of these polymorphisms indicated that the TNFalpha-308 G/A + IFNgamma+874 A/T + IL10-1082 G/G genotype increased the risk by 1.5 fold. CONCLUSIONS: The results of our study indicate an association between cytokine gene polymorphisms and the risk of NSCLC in an Indian population. PMID- 27282613 TI - Bifurcation lesions: no need to implant two stents when one is sufficient! PMID- 27282612 TI - Updated European Heart Rhythm Association practical guide on the use of non vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary. AB - In 2013, the European Heart Rhythm Association (EHRA) published a Practical Guide on the use of non-VKA oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) (Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm A. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-2106). The document received widespread interest, not only from cardiologists but also from neurologists, geriatricians, and general practitioners, as became evident from the distribution of >350 000 copies of its pocket version (the EHRA Key Message Booklet) world-wide. Since 2013, numerous new studies have appeared on different aspects of NOAC therapy in AF patients. Therefore, EHRA updated the Practical Guide, including new information but also providing balanced guiding in the many areas where prospective data are still lacking. The outline of the original guide that addressed 15 clinical scenarios has been preserved, but all chapters have been rewritten. Main changes in the Update comprise a discussion on the definition of 'non-valvular AF' and eligibility for NOAC therapy, inclusion of finalized information on the recently approved edoxaban, tailored dosing information dependent on concomitant drugs, and/or clinical characteristics, an expanded chapter on neurologic scenarios (ischaemic stroke or intracranial haemorrhage under NOAC), an updated anticoagulation card and more specifics on start-up and follow-up issues. There are also many new flow charts, like on appropriate switching between anticoagulants (VKA to NOAC or vice versa), default scenarios for acute management of coronary interventions, step-down schemes for long-term combined antiplatelet-anticoagulant management in coronary heart disease, management of bleeding, and cardioversion under NOAC therapy. The Updated Guide is available in full in EP Europace (Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, Advisors. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507), while additional resources can be found at the related ESC/EHRA website (www.NOACforAF.eu). PMID- 27282614 TI - Is it time to take bare metal stents off the catheter laboratory shelf? PMID- 27282615 TI - The race for higher sensitivity troponins, but for what prize? PMID- 27282616 TI - Serum micronutrients and prealbumin during development and recovery of chemotherapy-induced peripheral neuropathy. AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse event. Nutritional status can become impaired in cancer patients, potentially contributing to neuropathy's evolution. Our aim was to evaluate serum micronutrients and prealbumin in a cohort of 113 solid-cancer patients receiving platinum and taxane compounds during the development and recovery of neuropathy, up to 1 year after finishing treatment. CIPN was graded according to Total Neuropathy Score((c)) and NCI.CTCv3 at T0 (baseline), T1 (1-3 months), and T12 (12 months) after chemotherapy. CIPN was classified as asymptomatic (< grade 2) or symptomatic (>=2). CIPN recovery was defined as >=1 grade improvement at T12. Symptomatic CIPN developed in 52% of patients. Symptomatic patients presented a higher increase in TNSc (p < 0.001), in TNSr((c)) (p < 0.001), and decrease in sural (p < 0.001) and radial nerve conduction (p < 0.001). No significant differences with any of the micronutrients were observed along T0-T1 period between severity or chemotherapy groups. By T12, symptomatic patients without recovery had a decrease in vitamin E levels (p = 0.019) and prealbumin (p = 0.062) compared with those symptomatic that improved. A correlation between the variation of vitamin E and prealbumin at T0-T1 (r = 0.626, p = 0.001) and T1-T12 (r = 0.411, p = 0.06) was observed. After chemotherapy treatment, the improvement of patients displaying symptomatic neuropathy is related to vitamin E and prealbumin serum levels. Our results suggest that nutritional status can play a role in CIPN recovery. PMID- 27282617 TI - Magnesium Sulfate as an Alternative In Vitro Anticoagulant for the Measurement of Platelet Parameters? AB - OBJECTIVES: There are conflicting reports on the reliable measurement of platelet count and mean platelet volume (MPV) using EDTA or citrate. The anticoagulant properties of magnesium sulfate (MgSO4) are known from the literature. The aim of this study was to evaluate MgSO4 as an in vitro anticoagulant for platelet count, MPV, platelet distribution width, and platelet activation. METHODS: Whole blood from volunteers was anticoagulated by EDTA, citrate, or MgSO4 Platelets were counted by the XE 5000 (Sysmex, Norderstedt, Germany) impedance and fluorescence optical technique. RESULTS: The mean impedance platelet counts were 227.7, 197.0, and 201.1 * 10(9)/L in EDTA-, citrate-, or MgSO4-anticoagulated blood, respectively. The counts were 4.7% higher (EDTA) after 3 hours of storage but 4% lower in citrate-anticoagulated blood. The counts in magnesium samples remained stable. The MPV was 10.4 fL (EDTA), 9.5 fL (citrate), and 9.3 fL (MgSO4). EDTA samples showed cell swelling within the first 3 hours. This was lower in citrate and only marginal in magnesium samples. High activation of platelets was observed only in EDTA samples. CONCLUSIONS: Magnesium anticoagulation might be advantageous for more reliable MPV measurements. Although platelet count is underestimated when the impedance method is used, the platelet count reveals similar results when measured by the fluorescent optical method. PMID- 27282618 TI - Long-term experiences with genetic consultation in people with hereditary breast and ovarian cancer. AB - PURPOSE: Advances in genetics and increased public awareness increased the demand for interdisciplinary genetic outpatient consultation (IOGC). Communicating cancer risk is complex, and ideally information transfer should be individualized. Although psychological experiences with genetic testing have been studied in detail, studies on long-term experiences with IOGC and information transfer are lacking. We assessed patients' understanding and satisfaction with IOGC in families at risk of hereditary breast and ovarian cancer (HBOC) with the aim of informing best clinical practice, improving compliance and informed decision-making. METHODS: Female counselees referred for IOGC between July 1, 2009 and July 1, 2011 were eligible. Data were collected using a 47-item postal questionnaire to assess sociodemographic, psychological, behavioral parameters. Overall satisfaction and personal usefulness of IOGC were assessed with a five point, and risk perception with a visual analog scale. Data were analyzed using Spearman rank, Wilcoxon U or Chi-squared test. RESULTS: 612 (72 %) of 849 women participated reported being highly satisfied (75 %, n = 430) and declared personal usefulness (73 %, n = 421) on average 3.5 years after IOGC. Women deemed "high risk" assessed their risk of developing BC as significantly higher than non high-risk counselees (3.2 versus 3.0, p = 0.00484). Risk perception was lower in BRCA1/2 mutation carriers than in women with unclassified variants or no mutation (2.8 versus 3.5 and 3.1, respectively). CONCLUSION: Women with an HBOC background have additional needs to achieve long-term satisfaction after IOGC. Prospective studies are required to optimize care for the increasing number of people who seek genetic consultation, particularly as the complexity of genetics knowledge increases. PMID- 27282620 TI - Sulfuriflexusmobilis gen. nov., sp. nov., a sulfur-oxidizing bacterium isolated from a brackish lake sediment. AB - A chemolithotrophic sulfur-oxidizing bacterium, strain aks1T, was isolated from sediment of a brackish lake in Japan. The cells were curved rod-shaped and Gram stain-negative. The G+C content of the genomic DNA was 53 mol%. The major components in the cellular fatty acid profile were C16 : 0 and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c). As electron donor for chemolithoautotrophic growth, strain aks1T oxidized thiosulfate, sulfide, and elemental sulfur. The strain could utilize oxygen and nitrate as an electron acceptor for thiosulfate oxidation. Growth was observed at a temperature range of 5-34 degrees C, with optimum growth at 30-32 degrees C. Growth of the strain was observed at a pH range of 6.4-8.7. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain is related to members of the family Granulosicoccaceae within the order Chromatiales, with sequence similarities around 92 %. On the basis of phylogenetic and phenotypic properties, strain aks1T represents a novel species of a new genus, for which the name Sulfuriflexus mobilis gen. nov., sp. nov. is proposed. The type strain of the type species is aks1T (=DSM 102939T=NBRC 111889T). PMID- 27282619 TI - Osteopontin regulates proliferation, apoptosis, and migration of murine claudin low mammary tumor cells. AB - BACKGROUND: Osteopontin is a secreted phosphoglycoprotein that is expressed by a number of normal cells as well as a variety of tumor cells. With respect to breast cancer, osteopontin has been implicated in regulating tumor cell proliferation and migration/metastasis and may serve as a prognostic indicator. However it remains unclear whether osteopontin has the same impact in all breast cancer subtypes and in particular, osteopontin's effects in claudin-low breast cancer are poorly understood. METHODS: cDNA microarrays and qRT-PCR were used to evaluate osteopontin expression in mammary tumors from MTB-IGFIR transgenic mice and cell lines derived from these tumors. siRNA was then used to determine the impact of osteopontin knockdown on proliferation, apoptosis and migration in vitro in two murine claudin-low cell lines as well as identify the receptor mediating osteopontin's physiologic effects. RESULTS: Osteopontin was expressed at high levels in mammary tumors derived from MTB-IGFIR transgenic mice compared to normal mammary tissue. Evaluation of cell lines derived from different mammary tumors revealed that mammary tumor cells with claudin-low characteristic expressed high levels of osteopontin whereas mammary tumor cells with mixed luminal and basal-like features expressed lower levels of osteopontin. Reduction of osteopontin levels using siRNA significantly reduced proliferation and migration while increasing apoptosis in the claudin-low cell lines. Osteopontin's effect appear to be mediated through a receptor containing ITGAV and not through CD44. CONCLUSIONS: Our data suggests that mammary tumors with a mixed luminal/basal-like phenotype express high levels of osteopontin however this osteopontin appears to be largely produced by non-tumor cells in the tumor microenvironment. In contrast tumor cells with claudin-low characteristics express high levels of osteopontin and a reduction of osteopontin in these cells impaired proliferation, survival and migration. PMID- 27282621 TI - Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register. AB - AIM: To investigate the relative safety of various glucose-lowering agents as add on medication to metformin in type 2 diabetes in an observational study linking five national health registers. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005 2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score. RESULTS: Of the 20 422 patients included in the study, 43% started on second-line treatment with sulphonylurea (SU), 21% basal insulin, 12% thiazolidinedione (TZD), 11% meglitinide, 10% dipeptidyl peptidase-4 (DPP-4) inhibitor, 1% glucagon-like peptide-1 (GLP-1) receptor agonist and 1% acarbose. At the index date, the mean patient age was ~60 years for all groups except the GLP-1 receptor agonist (56.0 years) and SU (62.9 years) groups. Diabetes duration and glycated haemoglobin levels were similar in all groups. When compared with SU, basal insulin was associated with an 18% higher risk and TZD with a 24% lower risk of mortality [HR 1.18 (95% CI 1.03-1.36) and 0.76 (95% CI 0.62-0.94)], respectively. DPP-4 inhibitor treatment was associated with significantly lower risks of CVD, fatal CVD, CHD, fatal CHD and CHF. CONCLUSIONS: This nationwide observational study showed that second-line treatment with TZD and DPP-4 inhibitor as add-on medication to metformin were associated with significantly lower risks of mortality and cardiovascular events compared with SU, whereas basal insulin was associated with a higher risk of mortality. PMID- 27282622 TI - Purification and Characterization of Recombinant Darbepoetin Alfa from Leishmania tarentolae. AB - Darbepoetin alfa is a biopharmaceutical glycoprotein that stimulates erythropoiesis and is used to treat anemia, which associated with renal failure and cancer chemotherapy. We herein describe the structural characterization of recombinant darbepoetin alfa produced by Leishmania tarentolae T7-TR host. The DNA expression cassette was integrated into the L. tarentolae genome through homologous recombination. Transformed clones were selected by antibiotic resistance, diagnostic PCRs, and protein expression analysis. The structure of recombinant darbepoetin alfa was analyzed by isoelectric focusing, ultraviolet visible spectrum, and circular dichroism (CD) spectroscopy. Expression analysis showed the presence of a protein band at 40 kDa, and its expression level was 51.2 mg/ml of culture medium. Darbepoetin alfa have 5 isoforms with varying degree of sialylation. The UV absorption and CD spectra were analogous to original drug (Aranesp), which confirmed that the produced protein was darbepoetin alfa. Potency test results revealed that the purified protein was biologically active. In brief, the structural and biological characteristics of expressed darbepoetin alfa were very similar to Aranesp which has been normally expressed in CHO. Our data also suggest that produced protein has potential to be developed for clinical use. PMID- 27282623 TI - Hematological predictors and clinical outcomes in cardiac surgery. AB - PURPOSE: The present study was to investigate if five values that are part of the hemogram analysis routinely checked before heart surgeries can be used as a high quality, quick, low-cost, and easy-to-use outcome predictor. METHODS: This investigation was a retrospective, observational, cross-sectional study. Univariate and multivariate logistic regression was used to identify independent predictors for combined adverse events. We enrolled 1500 consecutive patients who underwent elective, on-pump, open-heart surgery from 2011 to 2014. Preoperative hemogram evaluation, red cell distribution width (RDW), mean platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were recorded. We classified combined adverse events (CAE) as (1) myocardial infarction, (2) cardiac reoperation, (3) prolonged mechanical ventilation, (4) prolonged hospital stay, (5) rehospitalization, or (6) mortality. RESULTS: It was found that several parameters obtained as part of the hemogram, namely RDW, MPV, PLR, and NLR, can predict, individually or in combinations, the outcomes in open-heart surgery patients. It was found that the prediction success of NLR (4.8 fold) was higher compared to RDW (1.8 fold) and MPV (1.5 fold). When the prediction success of the combined parameters was investigated, the NLR-RDW (4.7 fold) pair was found higher in the prediction of CAE occurrence. The predictive success of the triple combination of NLR-MPV-RDW (5.5 fold) was higher than other combinations. CONCLUSIONS: The triple combination of parameters obtained as part of the hemogram, NLR-RDW-MPV, indicated a much more predictive power than two parameters coupled. This combination of three parameters, NLR-RDW-MPV, is to be considered as a sensitive, high-quality, low-cost outcome prediction marker for cardiac surgery patients that is less time consuming and easy to use. PMID- 27282624 TI - Preload dependence and hypotension: One of the causes and one of the consequences of poor tolerance of intermittent hemodialysis in the ICU? PMID- 27282625 TI - Efficacy of Inhaled Levalbuterol Compared to Albuterol in Horses with Recurrent Airway Obstruction. AB - BACKGROUND: The (R)-enantiomer of racemic albuterol (levalbuterol) has bronchodilatory properties whereas the (S)-enantiomer causes adverse effects in human airways, animal models, and isolated equine bronchi. Levalbuterol is commercially available and improves pulmonary function of asthmatic patients with a longer duration of effect than albuterol. OBJECTIVE: To determine the dose at which inhaled levalbuterol produces maximal bronchodilatory effect (EDmax) and determine its duration of action in recurrent airway obstruction (RAO)-affected horses in comparison to racemic albuterol. ANIMALS: Nine horses with inducible and reversible RAO. METHODS: Randomized, crossover trial. Horses were challenged with moldy hay to induce airway obstruction. Horses were treated with nebulized albuterol or levalbuterol chosen randomly. Pulmonary function testing (PFT) was measured before and for up to 3 hours after bronchodilatation challenge. Maximum change in transpulmonary pressure (DPmax ) was measured to assess the dose effect and duration of action of each drug. After a 24 hours washout period, the bronchodilatation challenge was repeated with the second bronchodilator. RESULTS: The duration of effect was 60 minutes for albuterol and 120 minutes for levalbuterol. The dose of bronchodilator EDmax was not significantly different between albuterol and levalbuterol (EDmax = 125.0 [125-125 MUg] and EDmax = 188 [125-188 MUg] respectively; P = .068). The magnitude of bronchodilatation was not significantly different between the 2 treatments (61.1 and 59.9% decrease in DPmax for albuterol and levalbuterol respectively; P = .86). CONCLUSIONS AND CLINICAL IMPORTANCE: Levalbuterol is as effective a bronchodilator as albuterol; although levalbuterol lasts twice as long as albuterol, its duration of action is still too short to make it practical for RAO treatment. PMID- 27282626 TI - Secondhand smoke in the operating room? Precautionary practices lacking for surgical smoke. AB - BACKGROUND: Consensus organizations, government bodies, and healthcare organization guidelines recommend that surgical smoke be evacuated at the source by local exhaust ventilation (LEV) (i.e., smoke evacuators or wall suctions with inline filters). METHODS: Data are from NIOSH's Health and Safety Practices Survey of Healthcare Workers module on precautionary practices for surgical smoke. RESULTS: Four thousand five hundred thirty-three survey respondents reported exposure to surgical smoke: 4,500 during electrosurgery; 1,392 during laser surgery procedures. Respondents were mainly nurses (56%) and anesthesiologists (21%). Only 14% of those exposed during electrosurgery reported LEV was always used during these procedures, while 47% reported use during laser surgery. Those reporting LEV was always used were also more likely to report training and employer standard procedures addressing the hazards of surgical smoke. Few respondents reported use of respiratory protection. CONCLUSIONS: Study findings can be used to raise awareness of the marginal use of exposure controls and impediments for their use. Am. J. Ind. Med. 59:1020-1031, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 27282627 TI - Body representation in children with hemiplegic cerebral palsy. AB - Clinical observations indicate that many children with hemiplegic cerebral palsy refrain from using or disregard the affected upper limb. The aim of the present study is to investigate deficits in different body representations (body schema, body structural description, and body image) in children with hemiplegic cerebral palsy (HCP) compared to typically-developing (TD) children. Three groups of children participated in this study: 42 TD children (aged 5.17-10.91 years), 23 children with right HCP (aged 5.83-10.92 years), and 22 children with left HCP (aged 5.67-10.90 years). The results demonstrate generalized deficits in all three body representations in children with HCP, and do not offer evidence for an effect of hemiplegia laterality. PMID- 27282628 TI - Interventional therapy for hypertension: Back on track again? AB - Treatment-resistant hypertension, or resistant hypertension, is defined as blood pressure that remains above target despite concurrent use of at least three antihypertensive agents from different classes at optimal doses, one of which should be a diuretic. Important considerations in the diagnosis of treatment resistant hypertension include the exclusion of pseudoresistance and the evaluation of potential secondary causes of hypertension and of concomitant conditions that maintain high blood pressure. The ability to diagnose true treatment-resistant hypertension is important for selection of patients who may be appropriately treated with an invasive therapy. Currently, there are three interventional approaches to treat resistant hypertension, namely: (1) reduction of the activity of the sympathetic nervous system by renal nerve ablation, (2) stimulation of baroreceptors and (3) creation of a peripheral arterial venous anastomosis. This review focuses on the rationale behind these invasive approaches and the clinical results. PMID- 27282629 TI - Erratum: Elastic spheres can walk on water. PMID- 27282630 TI - Effects of age, education, and gender on verbal fluency in healthy adult Arabic speakers in Egypt. AB - The objective of this study is to establish the effects of age, gender, and education and to provide preliminary normative data for letter and category fluency tasks in the Egyptian Arabic-speaking population. We evaluated 139 cognitively healthy volunteers aged 20-93 by adapting the letter and category verbal fluency tasks for the Egyptian population. On the letter fluency task, mean number of words generated in one-minute beginning with the Arabic letter "Sheen" (pronounced "sh") was 8.14 words per minute (SD = 3.25). Letter fluency was significantly influenced by education. On category fluency tasks, mean number of animal names generated in one minute was 14.63 words (SD = 5.28). Category fluency was significantly influenced by age and education. We were able identify that age significantly affects category fluency while education significantly affected both letter and category fluency. We were also able to provide preliminary normative data for both tasks in the Egyptian population. PMID- 27282633 TI - PKCdelta stabilizes TAp63 to promote cell apoptosis. PMID- 27282631 TI - Transferring intercellular signals and traits between cancer cells: extracellular vesicles as "homing pigeons". AB - Extracellular vesicles are cell-derived vesicles, which can transport various cargos out of cells. From their cell of origin, the content molecules (proteins, non-coding RNAs including miRNAs, DNA and others) can be delivered to neighboring or distant cells and as such extracellular vesicles can be regarded as vehicles of intercellular communication or "homing pigeons". Extracellular vesicle shuttling is able to actively modulate the tumor microenvironment and can partake in tumor dissemination. In various diseases, including cancer, levels of extracellular vesicle secretion are altered resulting in different amounts and/or profiles of detectable vesicular cargo molecules and these distinct content profiles are currently being evaluated as biomarkers. Apart from their potential as blood-derived containers of specific biomarkers, the transfer of extracellular vesicles to surrounding cells also appears to be involved in the propagation of phenotypic traits. These interesting properties have put extracellular vesicles into the focus of many recent studies.Here we review findings on the involvement of extracellular vesicles in transferring traits of cancer cells to their surroundings and briefly discuss new data on oncosomes, a larger type of vesicle. A pressing issue in cancer treatment is rapidly evolving resistance to many initially efficient drug therapies. Studies investigating the role of extracellular vesicles in this phenomenon together with a summary of the technical challenges that this field is still facing, are also presented. Finally, emerging areas of research such as the analysis of the lipid composition on extracellular vesicles and cutting-edge techniques to visualise the trafficking of extracellular vesicles are discussed. PMID- 27282634 TI - Activation of cannabinoid CB1 receptors in the ventral hippocampus improved stress-induced amnesia in rat. AB - The ventral hippocampus (VH) has a high distribution of cannabinoid CB1 receptors which are important in modulating stress responses. Stress exposure activates the hypothalamic-pituitary-adrenal axis (HPA) which can impact hippocampal formation to change hippocampus-based memories. The purpose of the present study was to determine the possible role of the VH cannabinoid CB1 receptors in stress-induced amnesia using a step-through passive avoidance procedure in male Wistar rats. In order to induce acute stress, the animals were placed on an elevated platform for different time periods (10, 20 and 30min). Our results indicated that post training 20 and 30min exposure to stress, but not 10min, induced amnesia. Post training microinjection of a cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 2.5-7.5ng/rat) into the VH (intra-VH) induced amnesia. Interestingly, post-training intra-VH microinjection of the same doses of ACPA improved stress-induced amnesia. On the other hand, post-training intra VH microinjection of a selective CB1 receptor antagonist, AM-251 (20-50ng/rat) with exposure to an ineffective stress (10min) potentiated the effect of stress on memory consolidation and induced amnesia. It should be noted that post training intra-VH microinjection of the same doses of AM-251 alone had no effect on memory consolidation. Our results revealed that post-training intra-VH microinjection of AM-251, prior to ACPA microinjection, inhibited the reversal effect of ACPA on acute elevated platform stress. Taken together, it can be concluded that exposure to post-training inescapable stress impaired memory consolidation. The impairing effects of stress on memory retrieval may be mediated by the VH cannabinoid CB1 receptors. PMID- 27282632 TI - National prospective cohort study of peritonsillar abscess management and outcomes: the Multicentre Audit of Quinsies study. AB - OBJECTIVES: To investigate variations in the management and outcomes of peritonsillar abscesses, and to develop a trainee collaborative network in the UK. METHODS: Data were collected prospectively on suspected peritonsillar abscess cases presenting over a 2-month period at 42 participating secondary care centres, covering a population of 16 million. The primary outcome was an adverse event at 30 days, defined as re-presentation or re-drainage. RESULTS: Eighteen per cent of the 325 cases experienced an adverse event. Follow-up data were valid for 90 per cent of cases. Regression analyses showed a significant reduction in adverse events in the 12 per cent of patients who were discharged within 12 hours, and there was no significant increase in adverse events for the 70 per cent receiving corticosteroids. CONCLUSION: Out-patient management of peritonsillar abscess is not commonly practised in the UK. Corticosteroid usage is common and appears safe. This study demonstrates that trainees working in collaboration can effectively deliver prospective multicentre cohort studies in the UK. PMID- 27282635 TI - Repeated exposure reduces the response to impulsive noise in European seabass. AB - Human activities have changed the acoustic environment of many terrestrial and aquatic ecosystems around the globe. Mounting evidence indicates that the resulting anthropogenic noise can impact the behaviour and physiology of at least some species in a range of taxa. However, the majority of experimental studies have considered only immediate responses to single, relatively short-term noise events. Repeated exposure to noise could lead to a heightened or lessened response. Here, we conduct two long-term (12 week), laboratory-based exposure experiments with European seabass (Dicentrarchus labrax) to examine how an initial impact of different sound types potentially changes over time. Naive fish showed elevated ventilation rates, indicating heightened stress, in response to impulsive additional noise (playbacks of recordings of pile-driving and seismic surveys), but not to a more continuous additional noise source (playbacks of recordings of ship passes). However, fish exposed to playbacks of pile-driving or seismic noise for 12 weeks no longer responded with an elevated ventilation rate to the same noise type. Fish exposed long-term to playback of pile-driving noise also no longer responded to short-term playback of seismic noise. The lessened response after repeated exposure, likely driven by increased tolerance or a change in hearing threshold, helps explain why fish that experienced 12 weeks of impulsive noise showed no differences in stress, growth or mortality compared to those reared with exposure to ambient-noise playback. Considering how responses to anthropogenic noise change with repeated exposure is important both when assessing likely fitness consequences and the need for mitigation measures. PMID- 27282636 TI - Corrigendum: Femtosecond X-ray absorption study of electron localization in photoexcited anatase TiO2. PMID- 27282638 TI - Zika virus: a new threat to the safety of the blood supply with worldwide impact and implications. PMID- 27282639 TI - Phytochemical and Pharmacological Investigations on Nymphoides indica Leaf Extracts. AB - Nymphoides indica (L.) Kuntze (Menyanthaceae) is traditionally used in the Indian subcontinent. However, scientific data reporting its constituents are poor. This study aimed at evaluating its phytochemical constituents and various biological activities. Phytochemical investigations of the extracts and fractions resulted in the isolation of 5 lipophilic compounds, i.e. azelaic (nonanedioic) acid (1) and 4-methyl-heptanedioic acid (3), hexadecanoic (2) and stearic acid (5) and the fatty alcohol hexadecanol (4); 3 seco-iridoids, i.e. 7-epiexaltoside (6), 6",7" dihydro-7-epiexaltoside (7) and menthiafolin (8); 3 flavonoids, i.e. 3,7-di-O methylquercetin-4'-O-beta-glucoside (9), 3-O-methylquercetin-7-O-beta-glucoside (10) and 3,7-di-O-methylquercetin (11); scopoletin (12) and ferulic acid (13); and the monoterpenoids foliamenthoic acid (14) and 6,7-dihydrofoliamenthoic acid methyl ester (15). Compounds 1-5 showed moderate antimicrobial activities, whereas compound 9 presented mild antiprotozoal activities against Trypanosoma brucei (IC50 8 MUM), Leishmania infantum (IC50 32 MUM) and Trypanosoma cruzi (IC50 30 MUM). Antiglycation activity was shown by compounds 7 (IC50 0.36 mM), 10 (IC50 0.42 mM) and 15 (IC50 0.61 mM). Finally alpha-glucosidase inhibition was shown by compounds 7, 9, 11 and 13-15. It could be concluded that N. indica leaf extracts possess mild to moderate antimicrobial, antiprotozoal, antioxidant and antidiabetic activities. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27282637 TI - IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation. AB - The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17 16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94-27.83; 95% CI) for IDH mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association. PMID- 27282641 TI - The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative - Update on progress. AB - The implementation of the ICH S7B and E14 guidelines has been successful in preventing the introduction of potentially torsadogenic drugs to the market, but it has also unduly constrained drug development by focusing on hERG block and QT prolongation as essential determinants of proarrhythmia risk. The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative was established to develop a new paradigm for assessing proarrhythmic risk, building on the emergence of new technologies and an expanded understanding of torsadogenic mechanisms beyond hERG block. An international multi-disciplinary team of regulatory, industry and academic scientists are working together to develop and validate a set of predominantly nonclinical assays and methods that eliminate the need for the thorough-QT study and enable a more precise prediction of clinical proarrhythmia risk. The CiPA effort is led by a Steering Team that provides guidance, expertise and oversight to the various working groups and includes partners from US FDA, HESI, CSRC, SPS, EMA, Health Canada, Japan NIHS, and PMDA. The working groups address the three pillars of CiPA that evaluate drug effects on: 1) human ventricular ionic channel currents in heterologous expression systems, 2) in silico integration of cellular electrophysiologic effects based on ionic current effects, the ion channel effects, and 3) fully integrated biological systems (stem-cell-derived cardiac myocytes and the human ECG). This article provides an update on the progress of the initiative towards its target date of December 2017 for completing validation. PMID- 27282640 TI - Multi-parametric assessment of cardiomyocyte excitation-contraction coupling using impedance and field potential recording: A tool for cardiac safety assessment. AB - INTRODUCTION: The ICH S7B guidelines recommend that all new chemical entities should be subjected to hERG repolarization screening due to its association with life-threatening "Torsades de Pointes" (TdP) arrhythmia. However, it has become evident that not all hERG channel inhibitors result in TdP and not all compounds that induce QT prolongation and TdP necessarily inhibit hERG. In order to address the limitations of the S7B/E14 guidelines, the FDA through a public/private partnership initiated the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative to examine the possible modification and refinement of the ICH E14/S7B guidelines. One of the main components of the CiPA initiative is to utilize a predictive assay system together with human cardiomyocytes for risk assessment of arrhythmia. METHOD: In this manuscript we utilize the xCELLigence(r) CardioECR system which simultaneously measures excitation-contraction coupling together with human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to assess the effect of 8 reference compounds across 3 different independent sites. These 8 compounds were part of Phase I CiPA validation study. RESULTS: Our data demonstrate that hERG channel blockers, such as E4031 and moxifloxacin, prolonged field potential duration (FPD) at low concentration and induced arrhythmic beating activity as measured by field potential (FP) recording and impedance (IMP) recordings at higher concentrations. On the contrary, nifedipine, an inhibitor of calcium channel, didn't disrupt the periodicity of cell beating and weakened cell contractile activity and shortened FPD. Multichannel inhibitors, such as flecainide, quinidine and mexiletine, not only increased FPD and induced arrhythmia but also significantly reduced the amplitude of FP spike. JNJ303, an IKs inhibitor, only affected FPD. Comparison of the compound effect on FPD across the 3 different sites is consistent in terms of trend of the effect with observed 3-10 fold differences in minimal effective concentration at which a minimum of 10% response is detected. In addition, pentamidine, a hERG trafficking inhibitor which induced irregular beating activity over a more prolonged duration of time was readily flagged in this assay system. Taken together, this multi-parameter assay using hiPSC-CMs in conjunction with simultaneous measurement of ion channel activity and contractility can be a reliable approach for risk assessment of proarrhythmic compounds. PMID- 27282642 TI - Effects of mechanical and chemical surface treatments on the resin-glass ceramic adhesion properties. AB - AIM: Intraoral repair of fractured ceramic restorations using resin composite is practical for dental treatment. In the present study, we investigated whether differences in surface treatments for glass ceramic would affect resin adhesion. METHODS: Leucite-reinforced glass ceramic plates (IPS Empress Esthetic) were ground with 320-grit silicon carbide paper, cleaned using phosphoric acid, and then etched with hydrofluoric acid (IPS Ceramic Etching Gel) or left unetched, and silanized using silane coupling agent (RelyX Ceramic Primer) or kept unsilanized. Either conventional (Adper Scotchbond Multi-Purpose) or universal (Scotchbond Universal) adhesive was used to bond the resin composite to ceramic surfaces. Specimens were subjected to microshear test after 37 degrees C water storage for 24 h, and fractured surfaces were examined. Ceramic surface hydrophobicity after treatments was verified with contact angle measurements. Data were analyzed using anova and Tukey's tests. RESULTS: Regardless of the adhesive tested, hydrofluoric acid-etched ceramics showed higher bond strengths. Ceramic primer application improved resin bonding, even in non-etched groups, and also influenced fractography (P < 0.001). Contact angles on ceramics treated with ceramic primer were higher than those treated with silane-containing universal adhesive (P < 0.001). CONCLUSIONS: Mechanical and chemical retentions contribute to resin adhesion to glass ceramic. Universal adhesive seems to not function in the same manner as a silane coupling agent. PMID- 27282643 TI - Disease burden attributed to alcohol: How methodological advances in the Global Burden of Disease 2013 study have changed the estimates in Sweden. AB - AIM: The Global Burden of Disease (GBD) study continuously refines its estimates as new data and methods become available. In the latest iteration of the study, GBD 2013, changes were made related to the disease burden attributed to alcohol. The aim of this study was to briefly present these changes and to compare the disease burden attributed to alcohol in Swedish men and women in 2010 using previous and updated methods. METHODS: In the GBD study, the contribution of alcohol to the burden of disease is estimated by theoretically assessing how much of the disease burden can be avoided by reducing the consumption of alcohol to zero. The updated methods mainly consider improved measurements of alcohol consumption, including less severe alcohol dependence, assigning the most severe injuries and removing the protective effect of drinking on cardiovascular diseases if combined with binge drinking. RESULTS: The overall disease burden attributed to alcohol in 2010 increased by 14% when using the updated methods. Women accounted for this overall increase, mainly because the updated methods led to an overall higher alcohol consumption in women. By contrast, the overall burden decreased in men, one reason being the lower overall alcohol consumption with the new methods. In men, the inclusion of less severe alcohol dependence resulted in a large decrease in the alcohol attributed disease burden. This was, however, evened out to a great extent by the increase in cardiovascular disease and injuries. CONCLUSIONS WHEN USING THE UPDATED GBD METHODS, THE OVERALL DISEASE BURDEN ATTRIBUTED TO ALCOHOL INCREASED IN WOMEN, BUT NOT IN MEN. PMID- 27282644 TI - Considerations in the use of microneedles: pain, convenience, anxiety and safety. AB - Transdermal delivery using microneedles is gaining increasing attention from pharmaceutical and cosmetic companies as one of the promising drug delivery methods. Microneedle products have recently become available on the market, and some of them are under evaluation for efficacy and safety. To be available in the market for cosmetic and therapeutic use, several factors should be considered, including pain, anxiety, convenience and safety. These factors are summarized and reviewed in this article according to type of microneedle. Various kinds of materials have been used for manufacturing microneedles and developing drug formulations for microneedles. Safety information about materials used for microneedles is summarized in terms of type of microneedles. In addition to their biocompatibility, mechanical safety is also discussed. This review can provide guidelines for designing microneedle products for proper use. PMID- 27282645 TI - Chemistry is a Key Science for the Future of India and the World. AB - The next Angewandte Symposium, which is dedicated to chemical biology and bioorganic chemistry, will take place on July 13, 2016 during the CRSI National Symposium in Chemistry. This is an occasion to reflect on the international nature and societal responsibility of science, and to place the focus on chemical research in India. The number of Communications from India submitted to Angewandte Chemie has increased by 140 % from 2010 to 2015, and the number published by as much as 325 % ... Read more in the Editorial by Thisbe Lindhorst. PMID- 27282646 TI - Adsorption of benzoxaboroles on hydroxyapatite phases. AB - Benzoxaboroles are a family of molecules that are finding an increasing number of applications in the biomedical field, particularly as a "privileged scaffold" for the design of new drugs. Here, for the first time, we determine the interaction of these molecules with hydroxyapatites, in view of establishing (i) how benzoxaborole drugs may adsorb onto biological apatites, as this could impact on their bioavailability, and (ii) how apatite-based materials can be used for their formulation. Studies on the adsorption of the benzoxaborole motif (C7H7BO2, referred to as BBzx) on two different apatite phases were thus performed, using a ceramic hydroxyapatite (HAceram) and a nanocrystalline hydroxyapatite (HAnano), the latter having a structure and composition more similar to the one found in bone mineral. In both cases, the grafting kinetics and mechanism were studied, and demonstration of the surface attachment of the benzoxaborole under the form of a tetrahedral benzoxaborolate anion was established using (11)B solid state NMR (including (11)B-(31)P correlation experiments). Irrespective of the apatite used, the grafting density of the benzoxaborolates was found to be low, and more generally, these anions demonstrated a poor affinity for apatite surfaces, notably in comparison with other anions commonly found in biological media, such as carboxylates and (organo)phosphates. The study was then extended to the adsorption of a molecule with antimicrobial and antifungal properties (3 piperazine-bis(benzoxaborole)), showing, on a more general perspective, how hydroxyapatites can be used for the development of novel formulations of benzoxaborole drugs. STATEMENT OF SIGNIFICANCE: Benzoxaboroles are an emerging family of molecules which have attracted much attention in the biomedical field, notably for the design of new drugs. However, the way in which these molecules, once introduced in the body, may interact with bone mineral is still unknown, and the possibility of associating benzoxaboroles to calcium phosphates for drug formulation purposes has not been looked into. Here, we describe the first study of the adsorption of benzoxaboroles on hydroxyapatite, which is the main mineral phase present in bone. We describe the mode of grafting of benzoxaboroles on this material, and show that they only weakly bind to its surface, especially in comparison to other ionic species commonly found in physiological media, such as phosphates and carboxylates. This demonstrates that administered benzoxaborole drugs are unlikely to remain adsorbed on hydroxyapatite surfaces for long periods of time, which means that their biodistribution will not be affected by such phenomena. Moreover, this work shows that the formulation of benzoxaborole drugs by association to calcium phosphates like hydroxyapatite will lead to a rapid release of the molecules. PMID- 27282647 TI - Micromechanical properties of strain-sensitive lyriform organs of a wandering spider (Cupiennius salei). AB - Highly sensitive lyriform organs located on the legs of the wandering spider Cupiennius salei allow the spider to detect nanometer-scale strains in the exoskeleton resulting from locomotion or substrate vibrations. Morphological features of the lyriform organs result in their specialization and selective sensitivity to specific mechanical stimuli, which make them interesting for bioinspired strain sensors. Here we utilize atomic force microscopy (AFM)-based force spectroscopy to probe nano-scale mechanical properties of the covering membrane of two lyriform organs found on Cupiennius salei: the vibration sensitive metatarsal lyriform organ (HS10) and the proprioreceptive tibial lyriform organ (HS8). Force distance curves (FDCs) obtained from AFM measurements displayed characteristic multi-layer structure behavior, with calculated elastic moduli ranging from 150MPa to 500MPa for different regions and indentation depths. In addition, we probed the lyriform organs with a large radius tip, which allowed for probing structural deformation by the application of high forces and large scale deformations without damaging the surface. The viscoelastic behavior of the sensor materials observed in this probing suggests mechanical relaxation times potentially playing a role in the time-dependent behavior of the lyriform organs. STATEMENT OF SIGNIFICANCE: Highly sensitive lyriform organs located on the legs of the wandering spider Cupiennius salei allow the spider to detect nanometer-scale strains in the exoskeleton resulting from locomotion or substrate vibrations. Morphological features of the lyriform organs result in their specialization and selective sensitivity to specific mechanical stimuli, which make them an interesting for bioinspired strain sensors. Here we utilize atomic force microscopy (AFM)-based force spectroscopy to probe nano-scale mechanical properties of the covering membrane of two lyriform organs found on Cupiennius salei: the vibration sensitive metatarsal lyriform organ (HS10) and the proprioreceptive tibial lyriform organ (HS8). Force distance curves (FDCs) obtained from AFM measurements displayed characteristic multi-layer structure behavior, with calculated elastic moduli ranging from 150MPa to 500MPa for different regions and indentation depths. The viscoelastic behavior of the sensor materials observed in this probing suggests mechanical relaxation times playing a role in the time-dependent behavior of the lyriform organs. PMID- 27282648 TI - BRAT1 mutations are associated with infantile epileptic encephalopathy, mitochondrial dysfunction, and survival into childhood. AB - We describe two siblings who were affected with early onset focal seizures, severe progressive postnatal microcephaly, muscular hypertonia, feeding problems and bouts of apnea, only minimal psychomotor development, as well as death in infancy and childhood. We identified compound heterozygous mutations in BRAT1 exons 5 (c.638_639insA) and 8 (c.1134+1G>A) in one affected child via next generation sequencing of the disease-associated genome followed by phenotype driven bioinformatic analysis. Sanger sequencing confirmed the presence of these mutations in both patients and a heterozygote status of the parents. Whereas the frameshift mutation (c.638_639insA) has been described in one family, the splice site mutation (c.1134+1G>A) is novel. In contrast to all cases published so far, one of our patients showed a considerably milder clinical course with survival into childhood. Investigation of a skeletal muscle biopsy showed a severely reduced COX enzyme histochemical staining, indicating mitochondrial dysfunction. Our data expand the clinical and mutational spectrum of the BRAT1-associated phenotype. (c) 2016 Wiley Periodicals, Inc. PMID- 27282649 TI - Spatiotemporal distribution of proliferation, proapoptotic and antiapoptotic factors in the early human limb development. AB - Involvement of proliferation and apoptosis in the human limb development was analyzed electronmicroscopically and immunohistochemically in histological sections of 8 human embryos, 4(th) -10(th) week old, using apoptotic (caspase-3, AIF, BAX), anti-apoptotic (Bcl-2) and proliferation (Ki-67) markers, and TUNEL method. The data were analyzed by Mann-Whitney test, Kruskal-Wallis and Dunn's post hoc test. Initially, developing human limbs consisted of mesenchymal core and surface ectoderm with apical ectodermal ridge (AER). During progression of development, strong proliferation activity gradually decreased in the mesenchyme (from 78% to 68%) and in the epithelium (from 62% to 42%), while in the differentiating finger cartilages proliferation was constantly low (26-7%). Apoptotic caspase-3 and AIF-positive cells characterized mesenchyme and AER at earliest stages, while during digit separation they appeared in interdigital mesenchyme as well. Strong Bcl-2 expression was observed in AER, subridge mesenchyme and phalanges, while BAX expression charaterized limb areas undergoing apoptosis. Ultrastructurally, proliferating cells showed mitotic figures, while apoptotic cells were characterized by nuclear fragmentation. Macrophages were observed around the apoptotic cells. We suggest that intense proliferation enables growth and elongation of human limb primordia, and differential growth of digits. Both caspase-3 and AIF-dependant pathways of cell death control the extent of AER and numer of cells in the subridge mesenchyme at earliest developmental stages, as well as process of digit separation at later stages of limb development. Spatio-temporal co-expresson of Bcl-2 and BAX indicates their role in suppression of apoptosis and selective stimulation of growth during human limb morphogenesis. PMID- 27282651 TI - Insight into the SEA amide thioester equilibrium. Application to the synthesis of thioesters at neutral pH. AB - The bis(2-sulfanylethyl)amide (SEA) N,S-acyl shift thioester surrogate has found a variety of useful applications in the field of protein total synthesis. Here we present novel insights into the SEA amide/thioester equilibrium in water which is an essential step in any reaction involving the thioester surrogate properties of the SEA group. We also show that the SEA amide thioester equilibrium can be efficiently displaced at neutral pH for accessing peptide alkylthioesters, i.e. the key components of the native chemical ligation (NCL) reaction. PMID- 27282650 TI - Identification of circulating microRNAs during the liver neoplastic process in a murine model of hereditary tyrosinemia type 1. AB - Hereditary tyrosinemia type 1 (HT1) is a severe inborn error of metabolism, impacting the tyrosine catabolic pathway with a high incidence of hepatocellular carcinoma (HCC). Using a HT1 murine model, we investigated the changes in profiles of circulating and hepatic miRNAs. The aim was to determine if plasma miRNAs could be used as non-invasive markers of liver damage in HT1 progression. Plasma and liver miRNAome was determined by deep sequencing after HT1 phenotype was induced. Sequencing analysis revealed deregulation of several miRNAs including let-7/miR-98 family, miR-21 and miR-148a, during manifestation of liver pathology. Three miRNAs (miR-98, miR-200b, miR-409) presenting the highest plasmatic variations among miRNAs found in both plasma and liver and with >1000 reads in at least one plasma sample, were further validated by RT-qPCR. Two of these miRNAs have protein targets involved in HT1 and significant changes in their circulating levels are detectable prior an increase in protein expression of alpha-fetoprotein, the current biomarker for HCC diagnosis. Future assessment of these miRNAs in HT1 patients and their association with liver neoplastic lesions might designate these molecules as potential biomarkers for monitoring HT1 damage progression, improving diagnosis for early HCC detection and the design of novel therapeutic targets. PMID- 27282652 TI - Neuro-oncology: Amino acid PET for brain tumours - ready for the clinic? PMID- 27282654 TI - In the News: Uniting Europe through neurology. PMID- 27282655 TI - Conjugated Microporous Polymers with Built-In Magnetic Nanoparticles for Excellent Enrichment of Trace Hydroxylated Polycyclic Aromatic Hydrocarbons in Human Urine. AB - Conjugated microporous polymers (CMPs), linked by a covalent bond to form an extension of the aromatic ring skeleton, are microporous materials characterized by a highly conjugated structure and high stability. The present study reported on a novel strategy for the synthesis of CMPs with built-in magnetic nanoparticles for excellent enrichment of trace hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in human urine. We modified Fe3O4 nanoparticles with boronic acid groups and then reacted the nanoparticles with reactive monomers of polyphenylene conjugated microporous polymer (PP-CMP) to anchor the magnetic components in the PP-CMP framework. Chemical bonding between Fe3O4 nanoparticles and PP-CMP networks, together with equally firm covalent linkage and rigidity of the PP-CMP network, endows the magnetic PP-CMP with remarkable chemical stability and durability, even in harsh conditions. Magnetic PP-CMP has the characteristics of high conjugation ability, highly porous structure, and magnetism, which makes it an ideal magnetic adsorbent for trace analytes with aromatic conjugation structure. The adsorption mechanism of OH-PAHs on magnetic PP-CMP was investigated and demonstrated that hydrophobic interaction was important for the contribution of interaction between adsorbents and target analytes, together with the assistance of pi-pi stacking interaction. For the application, the magnetic PP-CMP was used for the enrichment of trace OH-PAHs in human urine of both smokers and nonsmokers in combination with high-performance liquid chromatography with fluorescence detection (HPLC-FLD). It showed good selectivity and excellent sensitivity to these OH-PAHs. Their detection limits were low and in the range of 0.01-0.08 MUg.L(-1). The OH-PAHs were detected with different amounts from 0.054 to 0.802 MUg.L(-1) in urine samples from smokers and nonsmokers. The recoveries were found to be 76.0%-107.8%. The results indicate that the magnetic PP-CMP offers an efficient enrichment method for trace OH-PAHs in human urine. PMID- 27282656 TI - Evaluation of Postmortem Cerebrospinal Fluid S100B Protein and Serotonin Levels: Comparison of Suicidal Versus Nonsuicidal Deaths in Konya, Turkey. AB - Although suicide is a preventable public health problem, objective assays for suicide risk are limited. In this study, it was aimed to determine levels of S100B protein and serotonin as a marker for risk of suicide. S100B protein and serotonin levels were investigated with ELISA method in the cerebrospinal fluid (CSF) in medicolegal autopsy cases, including those of suicide cases (n = 32) and nonsuicide cases (n = 56). The CSF S100B levels were higher (9.3 +/- 2.9 ng/mL vs. 5.4 +/- 2.0 ng/mL), and serotonin levels were lower (10.4 +/- 4.9 ng/mL vs. 19.0 +/- 5.7 ng/mL) in suicide group than nonsuicide group (p < 0.05). There was no correlation between S100B protein and serotonin levels with gender, age groups, postmortem interval, and cause of death. It is concluded that both S100B protein and serotonin in CSF may be useful for determination of suicide risk. PMID- 27282657 TI - Biofluids and other techniques: general discussion. PMID- 27282653 TI - Genetic variants in Alzheimer disease - molecular and brain network approaches. AB - Genetic studies in late-onset Alzheimer disease (LOAD) are aimed at identifying core disease mechanisms and providing potential biomarkers and drug candidates to improve clinical care of AD. However, owing to the complexity of LOAD, including pathological heterogeneity and disease polygenicity, extraction of actionable guidance from LOAD genetics has been challenging. Past attempts to summarize the effects of LOAD-associated genetic variants have used pathway analysis and collections of small-scale experiments to hypothesize functional convergence across several variants. In this Review, we discuss how the study of molecular, cellular and brain networks provides additional information on the effects of LOAD-associated genetic variants. We then discuss emerging combinations of these omic data sets into multiscale models, which provide a more comprehensive representation of the effects of LOAD-associated genetic variants at multiple biophysical scales. Furthermore, we highlight the clinical potential of mechanistically coupling genetic variants and disease phenotypes with multiscale brain models. PMID- 27282658 TI - Chemical screening identifies the beta-Carboline alkaloid harmine to be synergistically lethal with doxorubicin. AB - Despite being an invaluable chemotherapeutic agent for several types of cancer, the clinical utility of doxorubicin is hampered by its age-related and dose dependent cardiotoxicity. Co-administration of dexrazoxane as a cardioprotective agent has been proposed, however recent studies suggest that it attenuates doxorubicin-induced antitumor activity. Since compounds of natural origin present a rich territory for drug discovery, we set out to identify putative natural compounds with the view to mitigate or minimize doxorubicin cardiotoxicity. We identify the DYRK1A kinase inhibitor harmine, which phosphorylates Tau that is deregulated in Alzheimer's disease, as a potentiator of cell death induced by non toxic doses of doxorubicin. These observations suggest that harmine or other compounds that target the DYRK1A kinase my offer a new therapeutic opportunity to suppress doxorubicin age-related and dose-dependent cardiotoxicity. PMID- 27282659 TI - Effects of brown seaweed polyphenols, alpha-tocopherol, and ascorbic acid on protein oxidation and textural properties of fish mince (Pagrosomus major) during frozen storage. AB - BACKGROUND: Frozen storage of minced fish is currently one of the most important techniques to maintain its functional properties. However, some deterioration does occur during frozen storage and cause quality loss. The effects of brown seaweed polyphenols, alpha-tocopherol, and ascorbic acid on lipid and protein oxidation and textural properties of red sea bream (Pagrosomus major) during 90 days of frozen storage at -18 degrees C were investigated. RESULTS: All added antioxidants at 1 g kg-1 resulted in significantly lower thiobarbituric acid reactive substances (TBARS) compared to the control during the 45 days of frozen storage. The antioxidants were also effective in retarding protein oxidation concerning to total sulfhydryl content and protein carbonyl content. Brown seaweed polyphenols and alpha-tocopherol significantly retarded the inactivation of Ca2+ -ATPase activity during the first 45 days, whereas ascorbic acid had no such effect. The antioxidant activity showed either an invariable or decrease trend after 45 days storage. Adding antioxidants had a significant effect on the breaking force of the gels during the frozen storage period. CONCLUSION: These results indicate that brown seaweed polyphenols and alpha-tocopherol can be used to prevent oxidative reactions and thus maintain the structure of the gel formed by fish mince during frozen storage. (c) 2016 Society of Chemical Industry. PMID- 27282660 TI - Neonatal Platelet Transfusions and Future Areas of Research. AB - Thrombocytopenia affects approximately one fourth of neonates admitted to neonatal intensive care units, and prophylactic platelet transfusions are commonly administered to reduce bleeding risk. However, there are few evidence based guidelines to inform clinicians' decision-making process. Developmental differences in hemostasis and differences in underlying disease processes make it difficult to apply platelet transfusion practices from other patient populations to neonates. Thrombocytopenia is a risk factor for common preterm complications such as intraventricular hemorrhage; however, a causal link has not been established, and platelet transfusions have not been shown to reduce risk of developing intraventricular hemorrhage. Platelet count frequently drives the decision of whether to transfuse platelets, although there is little evidence to demonstrate what a safe platelet nadir is in preterm neonates. Current clinical assays of platelet function often require large sample volumes and are not valid in the setting of thrombocytopenia; however, evaluation of platelet function and/or global hemostasis may aid in the identification of neonates who are at the highest risk of bleeding. Although platelets' primary role is in establishing hemostasis, platelets also carry pro- and antiangiogenic factors in their granules. Aberrant angiogenesis underpins common complications of prematurity including intraventricular hemorrhage and retinopathy of prematurity. In addition, platelets play an important role in host immune defenses. Infectious and inflammatory conditions such as sepsis and necrotizing enterocolitis are commonly associated with late-onset thrombocytopenia in neonates. Severity of thrombocytopenia is correlated with mortality risk. The nature of this association is unclear, but preclinical data suggest that thrombocytopenia contributes to mortality rather than simply being a proxy for disease severity. Neonates are a distinct patient population in whom thrombocytopenia is common. Their unique physiology and associated complications make the risks and benefits of platelet transfusions difficult to understand. The goal of this review was to highlight research areas that need to be addressed to better understand the risks and benefits of platelet transfusions in neonates. Specifically, it will be important to identify neonates at risk of bleeding who would benefit from a platelet transfusion and to determine whether platelet transfusions either abrogate or exacerbate common neonatal complications such as sepsis, chronic lung disease, necrotizing enterocolitis, and retinopathy of prematurity. PMID- 27282661 TI - Comparison of Tunable Diode Laser Absorption Spectroscopy and Isothermal Micro calorimetry for Non-invasive Detection of Microbial Growth in Media Fills. AB - Two methods were investigated for non-invasive microbial growth-detection in intact glass vials as possible techniques for automated inspection of media filled units. Tunable diode laser absorption spectroscopy (TDLAS) was used to determine microbially induced changes in O2 and CO2 concentrations within the vial headspaces. Isothermal microcalorimetry (IMC) allowed the detection of metabolic heat production. Bacillus subtilis and Streptococcus salivarius were chosen as test organisms. Parameters as robustness, sensitivity, comparability and time to detection (TtD) were evaluated to assess method adequacy. Both methods robustly detected growth of the tested microorganisms within less than 76 hours using an initial inoculum of <10CFU. TDLA turned out to be less sensitive than TDLA and IMC, as some false negative results were observed. Compared to the visual media-fill examination of spiked samples, the investigated techniques were slightly slower regarding TtD. Although IMC showed shorter TtD than TDLAS the latter is proposed for automating the media-fill inspection, as larger throughput can be achieved. For routine use either TDLA or a combination of TDLA and TDLA should be considered. IMC may be helpful for replacing the sterility assessment of commercial drug products before release. PMID- 27282662 TI - Natural remedies used by Bunong people in Mondulkiri province (Northeast Cambodia) with special reference to the treatment of 11 most common ailments. AB - ETHNOPHARMACOLOGICAL RELEVANCE: In this paper we present a comprehensive ethnomedicinal study conducted in Mondulkiri province. Traditional knowledge about natural medicine (plants, animals, mushrooms) was investigated in Cambodia's largest indigenous community: the Bunong people. The survey aims to document the medicinal plant use of this ethnic, by focusing on the eleven most frequent diseases encountered in the area, in order to highlight species that could be recommended in public health programs. MATERIALS AND METHODS: During the years 2013 and 2014, 202 villagers were interviewed in 28 villages from the five districts in Mondulkiri. Two types of methodology were employed: (1) an ethnobotanical field survey (walk-in-the-wood interviews) and (2) semi-structured household interviews with a special emphasis on the treatment of 11 most common ailments encountered in the area. Medicinal plants and mushrooms were collected and identified together with medicinal animals. The factor informant consensus (FIC) and fidelity level (FL) were calculated. RESULTS: Bunong people use a total of 214 plants belonging to 72 families, 1 mushroom and 22 animal species in their traditional healthcare practices in order to treat 51 different ailments. Among the medicinal plants, Fabaceae was the most predominant family; Chromolaena odorata (L.) R.M. King and H.Rob. (Asteraceae), Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae) and Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) were the most cited medicinal plants; and four ailments (cold/fever, diarrhea, postpartum disorders and stomachache) were described as major ailments in the community. The root was the most important part of plants used, and decoction was the most cited method of preparation. During our survey, we also discovered a "new to science" plant species called Ardisia mondulkiriensis Hul and Chassagne, and we recorded for the second time the plant species recently described, Solanum sakhanii Hul. CONCLUSION: Most of the species reported for the treatment of the 11 most frequent ailments have already been proven to be efficient and safe. Furthermore, 10 plant species are reported for the first time as medicinal and some of them are widely used in the community. Further pharmacological and phytochemical investigations should be undergone to assess the pharmaceutical potential of these species. While undergoing considerable changes, Bunong people have maintained extensive traditional medicine knowledge. As this indigenous hill tribe depend mainly on natural remedies for their daily healthcare, environmental preservation is of high importance for the community. PMID- 27282663 TI - Mentha longifolia protects against acetic-acid induced colitis in rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Mentha longifolia L (Wild Mint or Habak) (ML) is used in traditional medicine in treatment of many gastrointestinal disorders. AIM OF THE STUDY: This study aimed to evaluate potential protecting effect of ML and its major constituent, eucalyptol, against acetic acid-induced colitis in rats, a model of human inflammatory bowel disease (IBD). MATERIALS AND METHODS: Rats were divided into ten groups (n=8) given orally for three days (mg/kg/day) the following: normal control, acetic acid-induced colitis (un-treated, positive control), vehicle (DMSO), sulfasalazine (500), ML extract (100, 500, 1000), and eucalyptol (100, 200, 400). After 24h-fasting, two ML of acetic acid (3%) was administered intrarectally. On the fifth day, serum and colonic biochemical markers, and histopathological changes were evaluated. RESULTS: Colitis significantly increased colonic myeloperoxidase activity and malonaldehyde level, and serum tumor necrosis factor-alpha, interleukin-6, and malonaldehyde levels while significantly decreased colonic and serum glutathione levels. All treatments (except ML 100, ML 1000, and eucalyptol 100) significantly reversed these changes where eucalyptol (400) showed the highest activity in a dose dependent manner. The colitis-induced histopathological changes were mild in sulfasalazine and eucalyptol 400 groups, moderate in ML 500 and eucalyptol 200 groups, and severe in ML 100, ML 1000, and eucalyptol 100 groups nearly similar to colitis-untreated rats. CONCLUSION: ML (in moderate doses) and eucalyptol (dose-dependently) exerted protective effects against acetic acid-induced colitis in rats possibly through antioxidant and antiinflammatory properties suggesting a potential benefit in treatments of IBD. To our knowledge this is the first report addressing this point. PMID- 27282664 TI - In vitro and in vivo anti-diabetic and hepatoprotective effects of edible pods of Parkia roxburghii and quantification of the active constituent by HPLC-PDA. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Parkia roxburghii G. Don. is a traditional medicinal plant and its pods are extensively used as food and medicine. It is believed by the traditional healers to have medicinal properties to treat diabetes, hypertension and urinary tract infections (Jamaluddin et al., 1994). MATERIALS AND METHODS: The methanolic extract of pods of P roxburghii and fractions were screened for their alpha-glucosidase and alpha-amylase inhibitory activity. Anti-hyperglycemic effects were studied on streptozotocin (45mg/kg b.w.) induced diabetes in albino rats (seven groups, n=7 n=6), using different doses for 14 days. Plasma glucose concentration (HbA1c) was analysed using whole blood, while SGOT, SGPT, TG, TC and uric acid were analysed using serum, employing commercial kits. Quantitative analysis of the major active constituent was carried out by HPLC-PDA. RESULTS: Bioactivity guided chemical investigation of the edible pods of P roxburghii identified sub-fraction EA-Fr 5 which significantly inhibited alpha-glucosidase (IC50 0.39+/-0.06 ugmL(-1)), reduced the blood glucose level to normal, and lowered the elevated levels of liver function enzymes SGOT and SGPT in STZ-induced diabetic rats. EA-Fr 5 was found to contain epigallocatechin gallate (1) and hyperin (2) which exhibited significantly higher alpha-glucosidase inhibitory potency with IC50 0.51+/-0.09 and 0.71+/-0.03uM respectively. EA-Fr 5 contained 379.82+/-2.90mg/g of EGCG, the major active constituent which manifests a broad spectrum of biological activities. CONCLUSION: The present investigation for the first time reports the occurrence of EGCG and hyperin in P roxburghii and substantiates the traditional use of pods of P roxburghii as dietary supplement for management of diabetes with significantly promising alpha-glucosidase inhibitory potency and anti hyperglycemic as well as hepatoprotective effects. PMID- 27282665 TI - Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-beta1/Smads signaling pathway modulation. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi decoction (HQD) is a well-known traditional Chinese herbal formulation, It is an effective treatment for consumptive disease and chronic liver diseases. It consists of Radix Astragali (Astragalus membranceus(Fisch.) Bge. Root, Huangqi) and Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch., root and rhizome, Gancao). Total astragalus saponins (AST) is a main component of Radix Astragali and glycyrrhizic acid(GA) is a main component of Radix Glycyrrhizae. Our primary results showed that the combination of AST and GA had an obvious synergistic effect in reducing liver collagen deposition and decreasing serum alanine aminotransferase (ALT) activity in dimethylnitrosamine (DMN)-induced liver fibrosis. AIM OF THE STUDY: Through in vivo and in vitro experiments, we aimed at investigating the key anti-fibrosis signal pathway TGF-beta1/Smads to further explore the synergistic mechanism of AST and GA. MATERIAL AND METHODS: Two hepatic fibrosis animal models, bile duct ligation-induced (BDL) and DMN-induced, were utilized. Rats were treated orally with AST, GA or AST/GA, with the effects evaluated via liver histopathology, hydroxyproline (Hyp) levels, and alpha-SMA expression. In the hepatic stellate cell line JS-1, cells were treated with AST/GA for 24h, followed by a cell viability assessment using Cell Counting Kit-8(CCK-8) and Real-time PCR and Western blot analysis of alpha-SMA, ColI and TGF-beta1/Smads signaling pathway related components. RESULTS: The AST/GA combination attenuated liver tissue inflammation, collagen deposition, Hyp levels, and alpha-SMA expression in both BDL-and DMN-stimulated hepatic fibrosis rats. In vitro results showed that the AST/GA combination significantly inhibited JS-1 cell viability, significantly suppressed alpha-SMA, ColI, TGF-beta1, Smad2 and Smad3 mRNA and protein expression, as well reduced p-Smad2/3. Compared with AST or GA treatment alone, the AST/GA combination significantly reduced Smad3 mRNA expression levels and TGF beta1, Smad3, and p-Smad2/3 protein levels. CONCLUSIONS: AST and GA synergistically alleviated both BDL-and DMN-induced hepatic fibrosis via TGF beta1/Smads signaling pathway inhibition in hepatic stellate cells. PMID- 27282666 TI - Anti-inflammatory and immunomodulatory effects of Critonia aromatisans leaves: Downregulation of pro-inflammatory cytokines. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Critonia aromatisans (Asteraceae), commonly known as "Chiople", is a cultivated species that is used in Mayan traditional medicine to treat inflammation, joint pain and rheumatism. AIM OF THE STUDY: To evaluate the in vivo and in vitro anti-inflammatory and immunomodulatory properties of aqueous and organic extracts prepared from Critonia aromatisans leaves. MATERIALS AND METHODS: Methanol, ethyl acetate, methylene chloride, hexanic, and aqueous extracts were obtained from the leaves of C. aromatisans. The anti-inflammatory properties of the extracts were tested in vivo to evaluate their ability to reduce the inflammatory response in the carrageenan-induced hind paw edema model in NIH mice. In addition, to explore the immunomodulatory effects of C. aromatisans, in vitro testing was performed to determine whether C. aromatisans leaf extracts are capable of decreasing macrophage production of nitric oxide (NO), tumour necrosis factor alpha (TNF-alpha), and cytokines IL-1beta, IL-6, and cyclooxygenase 2 (COX-2) without affecting macrophage viability. RESULTS: Single orally administered doses (100mg/kg or 200mg/kg) of a hexanic extract of C. aromatisans leaves significantly reduced carrageenan-induced paw edema in mice (P<0.001) by 76% and 84%, respectively. The effect of the extract in this model was generally comparable to those of the standard drugs used. In the in vitro determination, the extracts reduced the amount of NO mainly at 500 and 1000MUg/mL. Hexanic extract and subfractions C, D, E, and F at 50 and 100MUg/mL produced the lowest concentration of mediators in culture supernatants (protein) and at the mRNA/gene level by the significant down-regulation of cytokines. These findings explain some of the anti-inflammatory activity of this species. Purification of fractions C and D allowed the complete identification of cyclocolorenone, stigmasterol and stigmasterol derivatives as some of their main components. CONCLUSION: A hexanic extract of C. aromatisans displayed anti inflammatory effects, validating the traditional practice of Mayan communities wherein an ointment with a petrolatum base, a non-polar substance, is used to treat inflammation. Additionally, C. aromatisans showed strong in vivo and in vitro activity, and one of the mechanisms of its anti-inflammatory response was shown to be inhibition of the production of NO and pro-inflammatory cytokines. The results of this study provide a pharmacological basis for the use of C. aromatisans leaves in the treatment of inflammatory disorders. The presence of stigmasterol and cyclocolorenone could be the responsibles of the anti inflammatory activity of this specie. Further studies should be done on the antioxidant and anti-inflammatory properties of cyclocolorenone. The results of this study provide a pharmacological basis for the use of C. aromatisans leaves in the treatment of inflammatory disorders. PMID- 27282668 TI - Veritas filia temporis: The origins of the idea of scientific progress. AB - The article provides insight into the epistemological and anthropological aspect of the origination of the idea of scientific progress. It focuses on the relationship between individual's limited lifetime and the immensity of nature. The basic assumption is that the idea of scientific progress offers a solution of the epistemological problem stemming from the finding that there is no (teleological) coincidence between human cognitive abilities and the extent of nature. In order to facilitate the understanding of the origin of the idea of scientific progress, I propose distinction between the descriptive and prescriptive concepts of progress. While the descriptive notion of progress expresses the cumulative character of scientific knowledge and the superiority of the present over preceding generations, the prescriptive concept pertains to progressivist epistemology directing scientific research at the future development of knowledge. This article claims that the prevalent concept in Antiquity was the descriptive concept of scientific progress. The prescriptive notion had developed only in ancient astronomy. Early modern science was faced with similar issues as ancient astronomy - mainly the empirical finding related to the inexhaustible character of nature. Consequently to the introduction of the idea of progress, the progress of sciences became a purpose in itself - hence becoming infinite. PMID- 27282667 TI - High-energy proton imaging for biomedical applications. AB - The charged particle community is looking for techniques exploiting proton interactions instead of X-ray absorption for creating images of human tissue. Due to multiple Coulomb scattering inside the measured object it has shown to be highly non-trivial to achieve sufficient spatial resolution. We present imaging of biological tissue with a proton microscope. This device relies on magnetic optics, distinguishing it from most published proton imaging methods. For these methods reducing the data acquisition time to a clinically acceptable level has turned out to be challenging. In a proton microscope, data acquisition and processing are much simpler. This device even allows imaging in real time. The primary medical application will be image guidance in proton radiosurgery. Proton images demonstrating the potential for this application are presented. Tomographic reconstructions are included to raise awareness of the possibility of high-resolution proton tomography using magneto-optics. PMID- 27282670 TI - This month in the journal: cardiology and other disciplines. PMID- 27282669 TI - The impact of therapeutic massage on adult residents living with complex and high level disabilities: A brief report. AB - BACKGROUND: Research into the effects of touch in disabled adults in residential care remains largely unexplored in the current literature. Evidence suggests however, that massage therapy may improve mood state, including anxiety and stress, reduce pain and improve sleep/wake behavior and fatigue. These benefits are of importance as they have substantial impact on quality of life. PURPOSE: This pilot study evaluated the effect of therapeutic massage on the quality of life of adults with complex care needs living in residential care. METHODS: Participants were recruited from three residential homes (Queensland, Australia) for 18-65 year olds with severe disability. 25 participants were recruited and received a massage program consisting of five weeks of twice weekly massages. Structured interviews were conducted pre-post intervention. Additionally, mood was ascertained preceding and following each massage session. RESULTS: Mood of participants improved markedly immediately following massage session (p < 0.05) and pre-massage mood was observed to increase over the study period. However, pre and post-intervention measures indicated massage did not improve pain, sleepiness, depression or stress levels or sustain positive mood three days post intervention. Participants' satisfaction with their current health significantly improved (Z = -2.51, p = 0.012), as did their satisfaction with their current happiness (Z = -2.06, p = 0.04), suggesting that massage therapy offered some improvement in quality of life. CONCLUSIONS: The results of this pilot indicates that massage may be of benefit to people living with high care needs and represents a practical innovation providing tactile stimulation that may be integrated into care. PMID- 27282672 TI - Circulating microRNAs in patients with ST-elevation myocardial infarction. AB - OBJECTIVE: The aim of this study was to evaluate the expression levels of cardiac related circulating microRNAs (miRNAs) in ST-elevation myo- cardial infarction (STEMI) patients. METHODS: This study has a prospective experimental cohort design. A total of 12 consecutive patients with acute chest pain within 12 h admit- ted to emergency department (STEMI group) and 13 adult patients with normal coronary angiography during the same period were enrolled (control group) in this study. Changes in the expression of miR-122, miR-208, miR-375, miR-22, miR-133b, miR-92b, miR-21, miR-133a, miR-423-5p, miR-27b, miR-30a-3p, miR-17, miR 30d, miR-642, and miR-95 were analyzed using quantitative reverse transcription polymerase chain reaction. Blood samples were collected before angiography and 24 h after angiography. Data were analyzed using the Statistical Package for the Social Sciences v19. RESULTS: The STEMI group included 12 patients (7 males) with an average age of 56.5+/-8.3 (range, 44-69) years. The control group included 13 patients (9 males) with an average age of 59+/-11 (range, 42-80) years. When fold differences were calculated for the miRNA expression values, only miR-30d and miR 423-5p expression levels in STEMI patients showed significant differences in expression levels compared with control patients. The miRNA levels were 2.3-fold higher for miR-30d (p=0.034) and 6.9-fold higher for miR-423-5p (p=0.017). There was no significant cor- relation between troponin I and miR-30d or miR-423-5p levels (p>0.05). CONCLUSION: In this study, the expression levels of miRNAs related to cardiac disease were evaluated in peripheral blood. The circulating miR- 423-5p and miR-30d levels in peripheral blood were found to be higher in STEMI cases than in the control group. Further studies should be conducted to evaluate their potential use as biomarkers in STEMI cases. PMID- 27282671 TI - Determinants of prevalence, awareness, treatment and control of high LDL-C in Turkey. AB - OBJECTIVE: High blood cholesterol is one of the main modifiable risk factors for cardiovascular diseases (CVDs). The aim of the study is to determine the factors associated with the prevalence, awareness, treatment, and control of high "low density lipoprotein-cholesterol" (LDL-C) among adults aged >=20 years in Turkey. METHODS: We used data from Chronic Diseases and Risk Factors Survey conducted in 2011-2012. The presence of high LDL-C, lipid-lowering treatment eligibility, and achievement of target LDL-C were defined according to the third Adult Treatment Panel guidelines on treatment of high cholesterol. Multivariate logistic regression analyses were performed to determine the associations between participant characteristics and high LDL-C prevalence, awareness, treatment, and control. RESULTS: Framingham risk score categorization was performed for 13121 individuals aged >=20 years. Approximately, 28% of the participants presented with high LDL-C. Among those with high LDL-C, 55.8% were aware of their situation; among those aware of high LDL-C, 46.9% were receiving lipid-lowering medication, and 50.6% of individuals who were receiving treatment achieved target LDL-C levels on the basis of their coronary heart disease (CHD) risk. Control of high LDL-C was negatively associated with the presence of diabetes mellitus (odds ratio: 0.36, 95% CI: 0.27-0.49, p<0.001). CONCLUSION: Despite the high awareness rates, there was a high proportion of adults who did not receive treatment or achieve recommended levels of LDL-C during treatment. The low treatment and control levels among individuals based on their CHD risk levels call for a better application of recommendations regarding personal preventive measures and treatments in Turkey. PMID- 27282674 TI - An aspect to the publication ethics subject in the open access online journals. PMID- 27282673 TI - Myocardial infarction as a thrombotic complication of myeloproliferative disorders. PMID- 27282675 TI - Successful sequential drug eluting balloon angioplasty to chronic total occluded popliteal artery in a patient with thromboangitis obliterans by PCR. PMID- 27282676 TI - Value of neutrophil-to-lymphocyte ratio and its combination with GRACE risk score in predicting PCI outcomes in acute coronary syndrome. PMID- 27282677 TI - Current studies about the energy drinks may not simulate the real life. PMID- 27282678 TI - Author's Reply. PMID- 27282679 TI - Nebivolol compared with metoprolol for erectile function in males undergoing coronary artery bypass graft. PMID- 27282680 TI - Author's Reply. PMID- 27282681 TI - Cardiac problem because of Zika virus infection: a possibility. PMID- 27282682 TI - Conference Report: The 2nd Symposium of sudden cardiac arrest survival. PMID- 27282683 TI - Rheumatic involvement of the cleft mitral valve. PMID- 27282684 TI - Cardiac metastasis of synovial sarcoma presenting with superior vena cava syndrome. PMID- 27282685 TI - Early failure of symphysis pubis plating. AB - INTRODUCTION: Operative fixation of a disrupted symphysis pubis helps return alignment and stability to a traumatized pelvic ring. Implant loosening or failure has been demonstrated to commonly occur at some subacute point during the postoperative period. The purpose of this study is to report on a series of patients with traumatic pelvic ring disruptions to determine the incidence and common factors associated with early postoperative symphyseal plate failure before 7 weeks. MATERIALS AND METHODS: 126 patients retrospectively identified with unstable pelvic injuries treated with open reduction and plate fixation of the symphysis pubis and iliosacral screw fixation. Preoperative and postoperative radiographs, computed tomography (CT) images, and medical chart were reviewed to determine symphyseal displacement preoperatively and postoperatively, time until plate failure, patient symptoms and symphyseal displacement at failure, subsequent symphyseal displacement, incidence of additional surgery, and patient weight bearing compliance. RESULTS: 14 patients (11.1%) sustained premature postoperative fixation failure. 13 patients had anteroposterior compression (APC) II injuries and 1 patient had an APC-III injury. Preoperative symphyseal displacement was 35.6 millimeters (mm) (20.8-52.9). Postoperative symphyseal space measurement was 6.3mm (4.7-9.3). Time until plate failure was 29days (5 47). Nine patients (64.2%) noted a pop surrounding the time of failure. Symphyseal space measurement at failure was 12.4mm (5.6-20.5). All patients demonstrated additional symphyseal displacement averaging 2.6mm (0.2-9.4). Two patients (14.2%) underwent revision. Four patients (28.5%) were non-compliant. CONCLUSION: Premature failure of symphysis pubis plating is not uncommon. In this series, further symphyseal displacement after plate failure was not substantial. The presence of acute symphyseal plate failure alone may not be an absolute indication for revision surgery. Making patient education a priority could lead to decreased postoperative non-compliance and potentially a decreased incidence of implant failure. Posterior pelvic ring fixation aides overall pelvic ring stability and may help minimize further displacement after early postoperative symphyseal plate failure. Further functional outcome and biomechanical studies surrounding early symphyseal plate failure are needed. PMID- 27282686 TI - Water-based lubricant as an adjunct to wound toilet: Validation of a technique by experiment. AB - INTRODUCTION: Metal debris can produce a foreign body inflammatory reaction or as third body wear in the situation of joint arthroplasty. We evaluate a simple method for reducing this debris using a sterile water-based lubricating gel. MATERIALS AND METHODS: Eight experimental surgical models consisting of porcine muscle overlying a polyethylene tube with a titanium locking plate and screws secured were constructed. Four models had water based lubricating gel applied to the wound edges, four were left without as controls. Image were then captured before and after irrigation from which the amount of debris could be quantified. RESULTS: The reduction of surface area covered by debris for models with water based gel was greater (p=0.001). The average reduction in surface area was 27.2% for the control group and 94.1% for the models covered with lubricating gel. CONCLUSION: We show that using a safe, inexpensive and easily available water based lubricating gel reduces the amount of embedded debris when burring metal implants using a high-speed burr. PMID- 27282687 TI - The injury trajectory for young people 16-24 years in the six months following injury: A mixed methods study. AB - BACKGROUND: Adolescents and young people are the population at greatest risk of injury and therefore injury-related mortality and morbidity. Inquiry into the injury trajectory of young people is needed to identify this group's specific needs for healthcare. This paper reports the integration of quantitative and qualitative findings from a sequential explanatory mixed methods study examining young people aged 16-24 years' experience and trajectory of traumatic physical injury in the initial six months. The aim of integration was to address the question: In what ways are injured young peoples' experiences and self-management during the initial six months of the injury trajectory impacted by their injury, family support, and provision of healthcare? METHODS: Key findings from epidemiological datasets on young person injuries from hospital and coronial databases (Phase 1) were combined with key findings from qualitative interviews with 12 injured young people and 10 family members (Phase 2). RESULTS: The integration of findings from Phase 1 and Phase 2 resulted in three new findings; [1] (Alfred Health, 2014). A young person's perception of the severity of their injury, as well as the amount of time spent in hospital, impacts substantially on the way in which they experience injury, and this is managed differently between genders; [2] (Newnam et al., 2014). Admission to an Intensive care unit, including the intensity and duration of care, is the primary influence on how a family will provide support to the young person in the inpatient period; and [3] (Lyons et al., 2010). Young people's perception and understanding of their recovery from injury is in contrast with how healthcare systems are structured to provide rehabilitation and recovery care. CONCLUSION: The injury trajectory and recovery process of young people in the six months following injury have been have conceptualised. These trajectories of recovery can inform the development of anticipatory guidance frameworks for clinicians and guide the provision of and planning for clinical services for injured young people. PMID- 27282688 TI - Functional and psychological outcomes of delayed lower limb amputation following failed lower limb reconstruction. AB - PURPOSE: The purpose of this study was to evaluate the functional and psychological outcomes of patients who underwent delayed lower limb amputation following failed limb salvage surgery. METHODS: This retrospective, descriptive study evaluated functional outcomes using the Sickness Impact Profile (SIP) and Short Form-36 (SF-36) in 12 patients. Inclusion criteria included patients who underwent limb reconstruction and delayed amputation between July 2006 and December 2014, with an age range between 18 and 80 years of age, the ability to ambulate independently, a time interval between the last salvage procedure and amputation greater than six months, and a minimum follow-up of 24 months. Patients were contacted via telephone by the principal investigator and both the Sickness Impact Profile (SIP) and Short Form-36 (SF-36) were completed. Descriptive analysis (means and standard deviation) was used to determine outcomes for both SIP and SF-36 health profiles. RESULTS: Ten patients who had amputations following failed reconstruction (2006-2014) with a mean age of 53+/ 10years were interviewed. Six patients had a SIP <5, three patients scored between five and 10 points and one scored >10 points. The main deficit on the SF 36 was in the physical component. The SF-36 scores demonstrated a mean score of 40.8+/-11.5 for the physical component, and 57.4+/-7.9 for the mental component. Three patients returned to work after amputation and continued performing their pre-injury duties as farmers. Three other patients returned to work, but were allocated to administrative duties. Two patients were pensioners at the time of their injuries, and the only female patient was a housewife. One patient went into early retirement. CONCLUSION: The results of this study strongly suggest that delayed amputation following failed limb salvage surgery can still result in good and satisfactory outcomes in the majority of patients and achieves results similar to early amputation and limb reconstruction techniques. PMID- 27282689 TI - Does the relative density of periarticular bone influence the failure pattern of intra-articular fractures? AB - INTRODUCTION: The architecture of joints almost certainly influences the nature of intra-articular fractures, and the concavity is much more likely to fail than the associated convexity. However, local differences in periarticular bone density potentially also plays a critical role. The purpose of this study was to investigate if there was any difference in periarticular bone density in intra articular fractures between the two opposing joint surfaces, comparing the convexity to the concavity. MATERIALS AND METHODS: We retrospectively identified a series of 1003 intra-articular fractures of the hip, knee, and ankle; 129 of these patients had previously undergone CT scanning during their routine clinical assessment. Periarticular bone density was assessed using Hounsfield Units (HU) as a measure of the composite density of the adjacent bone. Bone density was compared between the opposite sides of each joint, to determine if a relationship exists between local bone density and the risk of articular surface fracture. RESULTS: There was a statistically significant difference in density between the two opposing surfaces, with the convexity 19% more dense than the concavity (p=0.0001). The knee exhibited the largest difference (55%), followed by the hip (18%); in the ankle, an inverse relationship was observed, and the concave surface was paradoxically denser (5%). There was no significant difference between those cases where the concavity failed in isolation compared to those where the convexity also failed (p=0.28). CONCLUSION: When the results were pooled for all three joints, there was a statistically significant higher local bone density demonstrated on the convex side of an intra-articular fracture. However, while this relationship was clearly exhibited in the knee, this was less evident in the other two joints; in the ankle the reverse was true, and the local bone adjacent to the concavity was found to have greater density. This suggests local bone density plays only a minor role in determining the nature of intra articular fractures. PMID- 27282690 TI - Comparison of clinical and radiologic outcomes between non-operative and operative treatment in 5th metatarsal base fractures (Zone 1). AB - The treatment of Zone 1 fractures of the 5th metatarsal base with >2mm of displacement remains controversial. We prospectively analyzed 29 patients with 5th metatarsal base fractures (Zone 1) during 2009-2014. Radiography was performed to assess the degree of fracture gap and metatarsal length. Patients with gaps of 2mm or less were treated conservatively using a short leg cast or splint (Group A), while patients with fracture gap >2mm were randomly assigned to one of two groups. Group B patients were managed with open reduction and internal fixation (ORIF), and Group C patients were placed in a short leg cast only. Visual analog scale (VAS) score and American orthopedic foot and ankle society (AOFAS) score were obtained at the initial consult and at the last follow-up after treatment; change of the 5th metatarsal length was also measured at the initial consult and after complete bony union. Our study demonstrated that radiographic union of all cases was observed with a significant decrease in VAS and AOFAS scores, regardless of the initial fracture gap and type of management. Additionally, there was no difference seen in final VAS scores for patients with longer metatarsals when compared to those in whom the metatarsals were unchanged or shortened. PMID- 27282691 TI - Good responsiveness with EuroQol 5-Dimension questionnaire and Short Form (36) Health Survey in 20-69 years old patients with a femoral neck fracture: A 2-year prospective follow-up study in 182 patients. AB - BACKGROUND: EQ-5D and SF-36 are two questionnaires used to measure health related quality of life (HRQoL). The responsiveness of these instruments has previously been evaluated in elderly populations with hip fracture but not in a younger population. The purpose was to evaluate the responsiveness of SF-36 and EQ-5D in a younger population with femoral neck fracture. METHODS: 182 patients aged 20-69 were consecutively included. HRQoL was measured by EQ-5D and SF-36 at 4, 12 and 24 months. Pain and function were measured by Harris Hip Score (HHS) on the same occasions. The responsiveness of EQ-5D and SF-36 was evaluated by calculation of two effect sizes; standardized effect size (SES) and standardized response mean (SRM), and by analysing how changes in score correlated to changes in function and subjective state of health. External responsiveness was also evaluated by calculating receiver operating characteristic curve and area under the curve. RESULTS: SES was large at four months for both EQ-5D and SF-36 (1.09 and 0.83 respectively) and moderate at the 12- and 24-month follow-ups. The correlation between changes (4-24 months) in HHS and changes in HRQoL were 0.44 for EQ-5D and 0.37 for SF-36. EQ-5D and SF-36 were both more sensitive than HHS in their ability to predict subjective improvements after a hip fracture. CONCLUSIONS: The effect sizes and the ability to follow and predict the external standard indicates that both EQ-5D and SF-36 have good internal and external responsiveness in this younger population with femoral neck fracture. The generic HRQoL questionnaires were superior to a hip-specific instrument in predicting the patients' subjective feelings of an improved state of health. EQ-5D is simple to administer and shows similar responsiveness as SF-36 and may be sufficient to use as an outcome measure in clinical trials. PMID- 27282693 TI - Biophysical insights into the membrane interaction of the core amyloid-forming Abeta40 fragment K16-K28 and its role in the pathogenesis of Alzheimer's disease. AB - The aggregation of amyloid-beta (Abeta) on neuronal membranes is implicated in both neuronal toxicity and the progression of Alzheimer's disease. Unfortunately, the heterogeneous environment that results from peptide aggregation in the presence of lipids makes the details of these pathways difficult to interrogate. In this study, we report an investigation of the membrane interaction of an Abeta fragment (K16LVFFAEDVGSNK28, KK13), which maintains the amyloidogenic nature of the full-length peptide and is implicated in membrane-mediated folding, through a combination of NMR spectroscopy and molecular dynamics simulations. Despite KK13's ability to form amyloids in solution, the monomer remains unstructured in the presence of lipid bilayers, unlike its full-length parent peptide. Additionally, NMR and molecular dynamics simulation results support that the presence of GM1 ganglioside, a lipid which strongly promotes binding between Abeta and lipid bilayers, promotes KK13 binding to but not folding on the membrane. Finally, we show that the peptide partitions between the membrane and aqueous solution based on the hydrophobicity of the N-terminal residues, regardless of lipid composition. These results support previous discoveries suggesting the importance of GM1 ganglioside in exacerbating membrane-driven aggregation while identifying the potential importance of C-terminal residues in membrane binding and folding, which has previously been unclear. PMID- 27282692 TI - Impact on the Incremental Cost-Effectiveness Ratio of Using Alternatives to EQ-5D in a Markov Model for Multiple Sclerosis. AB - OBJECTIVES: This study responds to a request in the National Institute for Health and Care Excellence (NICE) guidance to assess the impact of using alternative sources of utility values, applied to multiple sclerosis (MS). METHODS: Incremental cost-effectiveness ratios (ICERs) were calculated using utility values based on UK and Dutch values of EQ-5D, two UK mappings and one Dutch mapping of EQ-5D and two condition-specific instruments: the UK eight-dimensional Multiple Sclerosis Impact Scale (MSIS-8D) and the Dutch Multiple Sclerosis Impact Scale Preference-Based Measure (MSIS-PBM). Deterministic and Monte-Carlo simulation-based ICERs were estimated for glatiramer acetate versus symptom management using a lifetime Markov model. RESULTS: For both UK and Dutch perspectives, mapped and condition-specific utility values expressed significantly higher quality of life for the worst health state of the model than did EQ-5D. The ICER of glatiramer acetate with EQ-5D was US$182,291 for The Netherlands and US$153,476 for the UK. Ratios for mapped and condition-specific utilities were between 20 and 60 % higher. CONCLUSION: The overestimation of quality of life of patients with MS by mapped EQ-5D or condition-specific utility values, relative to observed EQ-5D, increases the ICER substantially in a lifetime Markov model. PMID- 27282695 TI - Closed venereology wards in the GDR. AB - BACKGROUND: At least 10 closed venereology wards existed in the GDR. To this date, the history of these wards has not yet been investigated thoroughly. OBJECTIVE: The history of the closed venereology wards in the GDR will be reconstructed by taking those in Halle (Saale) and Leipzig-Thonberg as examples. At the centre of the examination are the daily routines, the medical treatment and the education of the women. METHODS: Extensive archival research was conducted and the historical sources were critically evaluated. Moreover, interviews were held with women who had been admitted against their will as well as with former physicians, nurses and administrative staff members of the closed venereology wards. RESULTS: In most cases, the women were taken at random and admitted to the closed venereology wards by the police. They were not informed about the purpose, type and possible side-effects of their medical treatment. It was performed without their consent and therefore constituted a violation of their physical integrity. Even though 70% of the women had not been diagnosed with a sexually transmitted disease (STD), all of them had to undergo a gynaecological examination on a daily basis. The daily routine was strict, and the women were kept under surveillance. The wards had the 'educative' goal of transforming the women into 'socialist personalities'. CONCLUSION: The women in the closed venereology wards fell victim to politicized medicine. Put differently, medical care was supplemented with educational intentions and concepts, the purpose of which was to transform 'suffering persons' into 'socialist personalities'. This disciplinary system was based on terror. The closed venereology wards were not all alike; in some wards the women had to carry out chores on a daily basis (Halle/Saale), while in other wards they were detained and isolated from the outside world (Leipzig-Thonberg). PMID- 27282697 TI - Smartphone patient monitoring post-laser resurfacing. AB - BACKGROUND/OBJECTIVES: Patients should be monitored post-laser resurfacing for reassurance and the early detection of adverse events. Smartphone monitoring in the post-laser resurfacing setting is an efficient and convenient tool that is well accepted by patients and dermatologists. The objective was to identify the benefits and barriers of, and patient attitudes towards, smartphone monitoring in the post-laser resurfacing setting. METHODS: A retrospective audit of 123 laser resurfacing patients was undertaken to determine the characteristics of this population. A web-based survey was used to determine patients' attitudes towards smartphone monitoring. RESULTS: The commonest indications for laser resurfacing were acne scarring and photoageing rejuvenation. 88% of patients either had no adverse outcomes or expected post-laser resurfacing side-effects such as erythema. 12% developed adverse effects requiring intervention. The survey showed that all patients who had used the smartphone monitoring service felt it was a positive initiative for post-laser patients. Of note, most patients not using the smartphone review service were simply unaware of its existence. Biases may have been introduced as staff were less likely to promote the review service to patients undergoing lower intensity procedures. CONCLUSIONS: Smartphone monitoring post-laser resurfacing is an efficient and convenient alternative to face-to-face review for both patients and dermatologists. As technology improves and patients' expectations increase we expect more patients will request teledermatology reviews in order to easily and rapidly access medical advice. PMID- 27282698 TI - Confirming PICC tip position during insertion with real-time information. AB - Peripherally inserted central catheters (PICCs) play a fundamental role in patient care in a variety of clinical and healthcare settings. Tip location is important for both safety and efficacy. New technologies may offer the possibility of safer, more efficient and more effective insertion. A prospective evaluation was carried out of a system providing real-time information on the tip's location, direction, and depth during insertion in a total of 488 patients at a single centre (65 patients in the initial study, plus follow-on case series reports in 423 patients). No tip malpositions were reported and, as a result, the institution has been able to waive the requirement for confirmatory chest X-ray after PICC insertion, thus minimising the delay before the PICC can be used and increasing staff and patient confidence in the procedure. PMID- 27282694 TI - Transcriptomic analysis of submergence-tolerant and sensitive Brachypodium distachyon ecotypes reveals oxidative stress as a major tolerance factor. AB - When excessive amounts of water accumulate around roots and aerial parts of plants, submergence stress occurs. To find the integrated mechanisms of tolerance, we used ecotypes of the monocot model plant Brachypodium distachyon to screen for genetic material with contrasting submergence tolerance. For this purpose, we used a set of previously studied drought sensitive/tolerant ecotypes and the knowledge that drought tolerance is positively associated with submergence stress. We decided to contrast aerial tissue transcriptomes of the ecotype Bd21 14-day-old plants as sensitive and ecotype Bd2-3 as tolerant after 2 days of stress under a long-day photoperiod. Gene ontology and the grouping of transcripts indicated that tolerant Bd2-3 differentially down-regulated NITRATE REDUCTASE and ALTERNATIVE OXIDASE under stress and constitutively up-regulated HAEMOGLOBIN, when compared with the sensitive ecotype, Bd21. These results suggested the removal of nitric oxide, a gaseous phytohormone and concomitant reactive oxygen species as a relevant tolerance determinant. Other mechanisms more active in tolerant Bd2-3 were the pathogen response, glyoxylate and tricarboxylic acid cycle integration, and acetate metabolism. This data set could be employed to design further studies on the basic science of plant tolerance to submergence stress and its biotechnological application in the development of submergence-tolerant crops. PMID- 27282702 TI - BJN AWARD RUNNER UP. PMID- 27282699 TI - Innovation in training for totally implanted port insertion. AB - This article discusses the use of fresh frozen cadavers as an innovative way to teach the procedure of totally implanted port insertion. In an attempt to increase the number of competent medical and nursing practitioners able to insert these devices, workshops have been devised and delivered at a university clinical anatomy skills centre. This method of teaching has had positive feedback from practitioners. PMID- 27282696 TI - Spatiotemporal SERT expression in cortical map development. AB - The cerebral cortex is organized into morphologically distinct areas that provide biological frameworks underlying perception, cognition, and behavior. Profiling mouse and human cortical transcriptomes have revealed temporal-specific differential gene expression modules in distinct neocortical areas during cortical map establishment. However, the biological roles of spatiotemporal gene expression in cortical patterning and how cortical topographic gene expression is regulated are largely unknown. Here, we characterize temporal- and spatial defined expression of serotonin (5-HT) transporter (SERT) in glutamatergic neurons during sensory map development in mice. SERT is transiently expressed in glutamatergic thalamic neurons projecting to sensory cortices and in pyramidal neurons in the prefrontal cortex (PFC) and hippocampus (HPC) during the period that lays down the basic functional neural circuits. We previously identified that knockout of SERT in the thalamic neurons blocks 5-HT uptake by their thalamocortical axons, resulting in excessive 5-HT signaling that impairs sensory map architecture. In contrast, here we show that selective SERT knockout in the PFC and HPC neurons does not perturb sensory map patterning. These data suggest that transient SERT expression in specific glutamatergic neurons provides area specific instructions for cortical map patterning. Hence, genetic and pharmacological manipulations of this SERT function could illuminate the fundamental genetic programming of cortex-specific maps and biological roles of temporal-specific cortical topographic gene expression in normal development and mental disorders. PMID- 27282706 TI - Postpartum Depression in a General Pediatric Practice: Practical Methods for Improving Screening and Referrals. AB - Postpartum depression (PPD) is a common problem in new mothers. Untreated PPD is associated with behavioral and developmental problems in children. We examined the effects of an educational session about PPD and modification of the electronic medical record (EMR) on providers' screening for PPD. An education session was given to the physicians and pre and post surveys compared comfort and self-reported screening. Following the EMR change, a retrospective chart review was conducted from three time periods: group 1-before the conference, group 2 after the conference but before EMR change, and group 3-after screening in the EMR. Documented screening increased from 0% in group 1, to 2% in group 2, to 74% in group 3 (P < .001). Ten percent screened positive, but only 14% had documented referrals to a provider for treatment. The combination of provider education and screening questions integrated into the EMR enhanced PPD screening rates among physicians in a busy practice. PMID- 27282707 TI - Examining the Colonization and Survival of E. coli from Varying Host Sources in Drainage Basin Sediments and Stormwater. AB - It is widely understood that stormwater drainage has a significant impact on the health of tidal creek systems via regular inputs of runoff from the surrounding watershed. Due to this hydrologic connection, contamination of the upstream drainage basin will have a direct effect on estuaries and tidal creeks that often act as receiving waters. This study focuses on the importance of drainage basin sediments as they enhance the persistence and transport of the fecal indicator bacteria E. coli within a watershed. Experiments presented use microcosm environments with drainage basin sediments and stormwater to investigate E. coli colonization of stagnant waters and to examine the importance of host sources to bacterial survival. A novel method for establishing microcosms using environmental sediments with in situ bacterial populations and sterile overlying waters is used to examine E. coli colonization of the water column in the absence of flow. Colonization of sterile sediment environments also is examined using two common host sources (human and avian). Each experiment uses sediments of varying grain size and organic content to examine the influence of physical characteristics on bacterial prevalence. Results suggest host source of bacteria may be more important to initial bacterial colonization while physical characteristics of drainage basin sediments better explains extended E. coli persistence. Findings also suggest an indirect control of water column bacterial concentration by sediment type and erodibility. PMID- 27282708 TI - Why Has HIV/AIDS Prevalence Increased in Iran? PMID- 27282709 TI - Diabetes and Cirrhosis Are Risk Factors for Hepatocellular Carcinoma After Successful Treatment of Chronic Hepatitis C. AB - BACKGROUND: Successful treatment of hepatitis C virus (HCV) infection reduces the risk for hepatocellular carcinoma (HCC), but a risk remains. Current guidelines recommend continued HCC surveillance after sustained virologic response (SVR) has been achieved. This study aimed to investigate risk factors and incidence rates for HCC after SVR in HCV patients with pretreatment advanced liver disease (Metavir stage F3/F4). METHODS: All patients with advanced liver disease successfully treated for HCV at Karolinska University Hospital during 1992-2013 (n = 399) were followed up for a median of 7.8 years. Data from national registries were used to minimize loss to follow-up. Incidence rates and hazard ratios (HRs) for development of HCC were calculated by Cox regression analysis. RESULTS: Seventeen patients developed HCC during 3366 person-years (PY) of follow up. The HCC incidence rate was 0.95 (95% confidence interval [CI], .57-1.6) and 0.15 (95% CI, .05-.49) per 100 PY for patients with pretreatment F4 and F3, respectively. Patients with pretreatment cirrhosis and diabetes had a HR to develop HCC of 6.3, and an incidence rate of 7.9 per 100 PY (95% CI, 3.3-19) during the first 2 years of follow-up. The risk for HCC decreased significantly 2 years after SVR had been achieved. CONCLUSIONS: Diabetes mellitus and cirrhosis are strong risk factors for HCC development after SVR has been achieved. The risk to develop HCC diminishes significantly 2 years after SVR. Patients without cirrhosis have a low risk to develop HCC after SVR, and the benefit of HCC surveillance for this group is questionable. PMID- 27282712 TI - Sharing Is Caring: International Sharing of Data Enhances Genomic Surveillance of Listeria monocytogenes. PMID- 27282710 TI - Willingness to Take, Use of, and Indications for Pre-exposure Prophylaxis Among Men Who Have Sex With Men-20 US Cities, 2014. AB - BACKGROUND: Pre-exposure prophylaxis (PrEP) is an effective prevention tool for people at substantial risk of acquiring human immunodeficiency virus (HIV). To monitor the current state of PrEP use among men who have sex with men (MSM), we report on willingness to use PrEP and PrEP utilization. To assess whether the MSM subpopulations at highest risk for infection have indications for PrEP according to the 2014 clinical guidelines, we estimated indications for PrEP for MSM by demographics. METHODS: We analyzed data from the 2014 cycle of the National HIV Behavioral Surveillance (NHBS) system among MSM who tested HIV negative in NHBS and were currently sexually active. Adjusted prevalence ratios and 95% confidence intervals were estimated from log-linked Poisson regression with generalized estimating equations to explore differences in willingness to take PrEP, PrEP use, and indications for PrEP. RESULTS: Whereas over half of MSM said they were willing to take PrEP, only about 4% reported using PrEP. There was no difference in willingness to take PrEP between black and white MSM. PrEP use was higher among white compared with black MSM and among those with greater education and income levels. Young, black MSM were less likely to have indications for PrEP compared with young MSM of other races/ethnicities. CONCLUSIONS: Young, black MSM, despite being at high risk of HIV acquisition, may not have indications for PrEP under the current guidelines. Clinicians may need to consider other factors besides risk behaviors such as HIV incidence and prevalence in subgroups of their communities when considering prescribing PrEP. PMID- 27282711 TI - Clinical and Epidemiological Evidence of the Red Queen Hypothesis in Pneumococcal Serotype Dynamics. AB - BACKGROUND: The Red Queen hypothesis is an evolutionary theory that describes the reciprocal coevolution of competing species. We sought to study whether introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) altered pneumococcal serotype dynamics among children with invasive pneumococcal disease (IPD) as predicted by the Red Queen hypothesis. METHODS: This study examined pneumococcal isolates (n = 641) obtained from children <18 years of age hospitalized with IPD from 1997 to 2014 in Utah. A review of the literature also identified several additional studies conducted in the United States and Europe that were used to test the external generalizability of our Utah findings. Simpson's index was used to quantify pneumococcal serotype diversity. RESULTS: In Utah, the introduction of PCV7 and PCV13 was associated with rapid increases in serotype diversity (P < .001). Serotypes rarely present before vaccine introduction emerged as common causes of IPD. Diversity then decreased (P < .001) as competition selected for the fittest serotypes and new evolutionary equilibriums were established. This pattern was also observed more broadly in the United States, the United Kingdom, Norway, and Spain. CONCLUSIONS: This vaccine-driven example of human/bacterial coevolution appears to confirm the Red Queen hypothesis, which reveals a limitation of serotype-specific vaccines and offers insights that may facilitate alternative strategies for the elimination of IPD. PMID- 27282713 TI - Most and Least Meaningful Learning Experiences in Marriage and Family Therapy Education. AB - Marriage and family therapy educators increasingly emphasize training competencies. What we know less about is what makes family therapy education meaningful to marriage and family therapy (MFT) graduate students and what does not. In this study, through an Internet survey, we explored the most and least meaningful learning experiences of 68 MFT graduate students and recent graduates of Commission on Accreditation for Marriage and Family Therapy Education accredited programs. We used thematic analysis to identify and illustrate resulting themes, which included the importance of experiential and personal components to learning, the professor-student alliance, tying theory to practice, and the experiences of students with their clients, among others. We discuss the implications of these findings to support family therapy education and offer tentative suggestions for formative discussions both within and across programs. Video Abstract is found in the online version of the article. PMID- 27282715 TI - From the Editor in Chief. PMID- 27282714 TI - Congenital Milia En Plaque. AB - Milia en plaque is a rare, benign, localized, entity typically seen in adults after the third decade of life. Although there have been a few cases described in children, we describe the first case in a newborn. PMID- 27282716 TI - About the Cover. PMID- 27282717 TI - Health Disparities in Pediatric Asthma: Comprehensive Tertiary Care Center Experience. AB - LOCATION: Study conducted at Nemours /Alfred I. duPont Hospital for Children, Wilmington, DE 19803 BACKGROUND: Although the treatment and management of asthma hasimproved over time, incidence and prevalence among children continues to rise in the United States. Asthma prevalence, health services utilization, and mortality rate demonstrate remarkable disparities. The underlying causes of these disparities are not fully understood. We aimed to examine racial/ethnic variances in pediatric asthma prevalence/admission. PATIENTS AND METHODS: We retrospectively reviewed data on 1070 patients and applied a cross-sectional design to assess asthma admission between 2010 and 2011. Information was available on race/ethnicity, sex, insurance status, severity of illness (SOI), and length of stay/hospitalization (LOS).Chi-square statistic was used for the association between race and other variables in an attempt to explain the racial/ethnic variance. RESULTS: The proportionate morbidity of asthma was highest amongCaucasians (40.92%) and African Americans (40.54%), intermediate among others (16.57%), and lowest among Asian (0.56%), American Indian/Alaska Native (0.28%), and Hawaiian Native/Pacific Islander (0.28%). Overall there were disparities by sex, with more boys (61.80%) diagnosed with asthma than girls (38.20%), chi2(7)=20.1, p=0.005. Insurance status, and SOI varied by race/ethnicity, but not LOS. Caucasian children were more likely to have private insurance, while African Americans and Hispanics were more likely to have public insurance (p<0.005). Asthma was more severe among non-Hispanic children, chi2(14)=154.6, p<0.001. While the overall readmission proportion was 2.8%, readmission significantly varied by race/ethnicity. CONCLUSION: Racial/ethnic disparities in asthma admission exist among children in the Delaware Valley. There were racial/ethnic disparities in insurance status, asthma severity, and sex differed by race/ethnicity, but not in length of hospitalization. PMID- 27282718 TI - The Efficacy of Self-Report Measures in Predicting Social Phobia in African American Adults. AB - Empirical literature pertaining to anxiety in African Americans has been relatively sparse. More recent studies indicate that the construct of social fear is different in African Americans than in non-Hispanic Whites. Although some of these studies have examined factor structure utilizing self-report measures of anxiety in African American samples, none to date have examined the clinical utility of these measures in predicting anxiety diagnoses, particularly social phobia. A total of sixty-five African American adults from the community completed the Fear Survey Schedule-Second Edition (FSS-II), Social Anxiety Interaction Scale (SIAS), Social Phobia Scale (SPS), and Albany Panic and Phobia Questionnaire (APPQ). The Anxiety Disorder Interview Schedule-Fourth Edition (ADIS-IV) was administered to all participants to specify differential diagnoses of anxiety and related disorders. Twenty-three African American adults were diagnosed with social phobia leaving 42 diagnostic controls. Results suggest that the social anxiety factors were highly predictive of a social phobia diagnosis (AUC=.84 to .90; CI .73-.98, p<.01) and sensitivity and specificity rates revealed optimal cutoff scores for each measure. The optimal cutoff scores reveal the clinical utility of the social fear factor from these measures in screening for social phobia in African Americans. Future direction and implications are discussed. PUBLICATION INDICES: Psychinfo, PubMed, Medline. PMID- 27282719 TI - Remembering the Basics: African American Youth and HIV Knowledge - Brief Report. AB - ACKNOWLEDGEMENTS: This research was supported by a grant from the Royalty Research Fund at the University of Washington. We thank all the youth, families, and community organizations for their participation. OBJECTIVE: The current work examined three HIV knowledge areas (i.e.,general knowledge, HIV-safe behaviors, HlV-risk behaviors) among African American youth living in two urban areas. METHODS: In a cross sectional sample of 142 African American youth ages11-17 years living in Chicago and Seattle, youth's HIV knowledge wasassessed using a 16 item survey adapted from the Youth AIDS Prevention Project and the Aban Aya Project. RESULTS: Multiple linear regression analyses examined the association among youth HIV knowledge and key demographic variables (i.e., age, gender, parent education, household income, and city). Overall HIV knowledge was low among all youth. Youth were most informed about general knowledge, followed by knowledge of HlV-risk behaviors. Youth were considerably misinformed about HIV safe behaviors. Generally, older youth and those living in Seattle were more informed about HIV than younger adolescents and youth living in Chicago. Household income and youth gender were unrelated to youth's HIV knowledge. However, parental education was related to youth's HIV-safe knowledge, with youth of more educated parents having less knowledge than youth with less educated parents. CONCLUSIONS: Findings from this study underscore the importance of continued attention to HIV knowledge as an important component of HIVprevention among African American youth. Accurate information about HIV is critical for prevention efforts. Prevention efforts should ensure that new generations of youth continue to be provided with knowledge about HIV risk and transmission. PUBLICATION INDEX: PubMed. PMID- 27282720 TI - Misdiagnosis of African-Americans with Psychiatric Issues - Part I. AB - PURPOSE: This article highlights issues of misdiagnosis in an African-American, adult clinical population by doing point prevalence, record review study within a comprehensive community mental health center. METHOD: Psychiatric evaluations of 330 patients were reviewed and clinically identifiable variables of: a) childhood Intellectual Disability (ID), special education, Attention Deficit Hyperactive Disorder (ADHD), or Autism/Pervasive Developmental Disorder (PDD); b) head injury causing Organic Brain Syndrome (OBS) or Temporal Lobe Epilepsy (TLE); c) a history of chronic substance abuse prior to the development of psychiatric symptoms; or d) childhood trauma causing Anxiety, Depression, and Panic Disorders were tabulated. RESULTS: Two hundred and twenty patients, who were free of the four variables, had a single psychiatric diagnosis and 18 had multiple co-morbid diagnoses. More than 25% (92/330) of the patients had the four variables in their histories. Four of the 92 patients had more than one variable in their history. Of the remaining 88 cases, 42 had psychiatric issues beginning in childhood (28 had history of ID, 4 had history of learning disabilities, 3 had history of ADHD, 7 had histories of Autism/PDD); 9 had histories of OBS or TLE; 20 had histories of substance abuse; and 18 had histories of extensive childhood trauma). CONCLUSIONS: Careful attention to common issues in African-Americans can inform the psychiatric diagnostic process pointing to prevention or treatment considerations that would benefit the African-American community at large. PMID- 27282721 TI - Misdiagnosis of African-Americans with Psychiatric Issues - Part II. AB - PURPOSE: The second "Misdiagnosis of African-Americans with Psychiatric Issues" article focuses on traumatic life experiences that meet a proposed criteria for Developmental Trauma Disorder (DTD).l METHOD: Psychiatric evaluations of 330 patients were reviewed and clinically identifiable variables of: a) childhood mental retardation (MR), special education, Attention Deficit Hyperactive Disorder (ADHD), or Autism/Pervasive Developmental Disorder (PDD); b) head injury causing Organic Brain Syndrome (OBS) or Temporal Lobe Epilepsy (TLE); c) a history of chronic substance abuse prior to the development of psychiatric symptoms; or d) childhood trauma causing Anxiety, Depression, and Panic Disorders were tabulated. RESULTS: In Part I,2-Reference Part I we learn that the above four variables did not influence two-thirds of the African-American patient's psychiatric diagnoses; however, excluding patients with multiple diagnoses, 26.7% of the patient's diagnoses were shaped by these variables. Of these, 20% (18 of 88 patients), or 5.5% of the total 330 patients, had diagnoses that were strongly influenced by childhood traumatic experiences. Accordingly, we present two case histories that explicate the psychopathology seen in African-Americans traumatized as children. CONCLUSIONS: This study helps to stress and confirm the importance of how understanding childhood traumatic experiences shape adult African-American psychopathology and the potential for misdiagnosis - an important factor for prevention and appropriate treatment of African-American patients with psychiatric issues. PMID- 27282722 TI - Exploring Donotion-related Knowledge Attitudes, Beliefs and Distrust Among African Americans. AB - Within the field of organ donation, multiple studies have shown differences in patterns of trust, however, it is unclear which elements are significantly related to donation decision making among African Americans. This study sought to disentangle the construct of trust by parceling out measures related to the healthcare system, the donation/allocation system, and the physician; and determine the relationship of these dimensions to attitudes toward organ and tissue donation. Cross-sectional survey data were gathered from 585 African American adults residing in the Atlanta metropolitan area. Results indicate that varying dimensions of trust function differently in their influence on attitudes toward donation. Our findings suggest that trust is critical to donation decision making and should be measured with a multidimensional approach, particularly among racial/ethnic groups with complex histories with the healthcare system. This study underlines the need for a more tailored, individualized approach to promoting organ and tissue donation among African Americans. ACKNOWLEDGEMENTS: We also thank Rianot Amzat, Mohua Basu and Rhonda DeLaremore for their assistance with data collection, cleaning, entry, and analysis. PMID- 27282723 TI - Caregiver's Health Locus of Control and Medication Adherence in Sickle Cell Disease. AB - ACKNOWLEDGEMENTS: The authors would like to thank Dr. Morisky for giving us permission to use the Morisky Medication Adherence Scale PURPOSE: To explore caregivers' Health Locus of Control's relationship to self-reported adherence to penicillin prophylaxis or hydroxyurea in children with sickle cell disease (SCD). PROCEDURE: A questionnaire-based study was conducted of caregivers of children with SCD who visited a comprehensive sickle cell center in an inner city hospital, who were either on penicillin prophylaxis or hydroxyurea or both. Multidimensional Health Locus of Control Scale (MHLC) and the Morisky Medication Adherence Scale (MMAS-8) questionnaires were used for the study. RESULTS: Caregivers of 43 children (27 on penicillin prophylaxis, 13 on hydroxyurea, and 3 on both) completed the MHLC and the MMAS-8. There was no significant difference in adherence between the penicillin and the hydroxyurea groups. The mean Powerful Others score of caregivers of the hydroxyurea only group (25.5+5.6) was higher than that of the penicillin only group (21.2+6.1, p=0.043). Regression analysis revealed an inverse relationship of Chance Locus of Control to adherence in the entire group (Beta = -0.306, R2=0.093, F[1,40]=4.12, p=0.049). CONCLUSION: Chance Locus of control may identify caregivers of children with SCD at risk for non adherence to treatment. PMID- 27282724 TI - Errors in Patient History in Hospital Records. AB - CONFLICT OF INTEREST: Ghan-Shyam Lohiya MD provided medico-legal opinions as a Qualified Medical Evaluator (Occupational Medicine & Toxicology) supporting a related workers' compensation death claim. Dr G. Lohiya received partial payments for his services from Gallagher Bassett Services Company (workers' compensation insurance adjuster for the patient's employer). Sonia Krishna MD, Sapna Lohiya and Sunita Lohiya MD: No actual or potential, real or perceived conflict of interest in the drugs, devices or procedures described in the enclosed manuscript. ABSTRACT: A patient died of renal failure related to treatment of a hand contusion with ibuprofen and valdecoxib. Her hospital records revealed several incorrect and mutually conflicting statements about seven historical items in the Initial Evaluation Reports authored by five treating physicians. There were errors of commission (relying on imperfect memory, acquiescing erroneous information), and errors of omission (failure to proofread transcribed reports, question and resolve contradictory statements in sister reports, obtain correct history, and review prior medical records). Such errors wrongly implied that patient had preexisting conditions (advanced renal failure, diabetes mellitus, hypertension, asthma and alcoholism) which caused her death, and negatively impacted her workers' compensation claim. Incorrect allergy history was also noted. Preventive measures are suggested. PROFESSIONAL PRESENTATION: At the 53rd Quarterly Grand Rounds in Costa Mesa, California. PMID- 27282725 TI - A Review of Concussion Management in the Young Adult; the Importance of Baseline Testing and Caregiver Education. AB - : Despite the increase in studies and media coverage, concussion continues to threaten the futures of young athletes and cause a great deal of concern among parents and practitioners. Questions continue regarding the management and return to play for injured adolescents and young adults, and regarding the long term consequences of repeated concussion in our youth. There appears to be a huge disparity between what health care professionals know and understand about concussion and what the average athlete and parent understands about what concussion is and the real risks involved. A review of current literature reveals a persistent lag between our knowledge and practice. This literature survey takes the athlete from the pre-participation sports physical, to the sidelines, to the doctor's office, to return to play and provides a comprehensive assessment of current recommendations. There is a significant need, especially in urban areas, for education and access to cheap and simple baseline functional assessments of adolescents and young adults. We recommend athletes be assessed at their yearly physical in order to properly determine their baseline function and readiness to return to play after concussion. Additionally, we recommend providing anticipatory guidance and a simple concussion evaluation tool to be used by parents and guardians to also annually assess a young person's baseline functional status and subsequent alterations. The goal of this review is to create an evidence-based, simple, cost-effective parental survey; increase awareness, understanding and diagnosis of concussion; and finally, expedited proper treatment and facilitate return to play. PUBLICATION INDICES: PubMed, lib.wayne.edu. PMID- 27282726 TI - Large Congenital Hydrocephalus:Extended Survival without Neurosurgery. AB - PROFESSIONAL PRESENTATION: This work was presented at the 57th Quarterly Grand Rounds at Fairview Developmental Center, Costa Mesa, California on October 17, 2012. ACKNOWLEDGMENT: Authors are grateful to Stephan Reynolds CRT, and Indira Makwana for records. CONFLICT OF INTEREST: None of the authors has any conflict of interest with the information provided in this article. ABSTRACT: We report the case of a 45-year-old patient with large congenital hydrocephalus. Patient was born prematurely at 26-weeks' gestation with a weight of 1.14Kg. His head circumferences have been: Birth, 27.9 cms; age 3-months, 40.6 cms; 18-months, 74 cms; 36-months, 80 cms; current, 88.4 cms (normal adult: 52-58 cms). During infancy, his prognosis was considered "terminal" due to rapid progression of severe hydrocephalus; therefore no neurosurgical intervention was undertaken. At 18-months' age, he was admitted to our developmental center where he is presently comfortable and clinically stable. Due to habitual unilateral decubitus, his head is now markedly flattened on the right (deformational plagiocephaly), and disproportionately long and narrow (scaphocephaly: occipitofrontal length 36.8 cms, biparietal width 12.5; ratio 2.9). We credit patient's extended survival to diligent professional care. INDICES USED: PubMed. PMID- 27282727 TI - Teaching Giants and Other Mentors of the Howard University: College of Medicine Class of 1952. AB - During the two decades following World War II, rapid changes occurred in medicine and in society as a whole in the United States including the establishment of the National Institutes of Health and the civil rights movement. This article profiles the teaching faculty of the Howard University College of Medicine that prepared the Class of 1952 for the decades that were to follow. PMID- 27282728 TI - History of the Family Practice Section National Medical Association. PMID- 27282729 TI - 4-amino-6-alkyloxy-2-alkylthiopyrimidine derivatives as novel non-nucleoside agonists for the adenosine A1 receptor. AB - Three 4-amino-6-alkyloxy-2-alkylthiopyrimidine derivatives (4-6) were investigated as potential non-nucleoside agonists at human adenosine receptors (ARs). When tested in competition binding experiments, these compounds exhibited low micromolar affinity (Ki values comprised between 1.2 and 1.9 MUm) for the A1 AR and no appreciable affinity for the A2A and A3 ARs. Evaluation of their efficacy profiles by measurement of intracellular cAMP levels revealed that 4 and 5 behave as non-nucleoside agonists of the A1 AR with EC50 values of 0.47 and 0.87 MUm, respectively. No clear concentration-response curves could be instead obtained for 6, probably because this compound modulates one or more additional targets, thus masking the putative effects exerted by its activation of A1 AR. The three compounds were not able to modulate A2B AR-mediated cAMP accumulation induced by the non-selective AR agonist NECA, thus demonstrating no affinity toward this receptor. PMID- 27282730 TI - Evaluation of bacterial diversity recovered from petroleum samples using different physical matrices. AB - Unraveling the microbial diversity and its complexity in petroleum reservoir environments has been a challenge throughout the years. Despite the techniques developed in order to improve methodologies involving DNA extraction from crude oil, microbial enrichments using different culture conditions can be applied as a way to increase the recovery of DNA from environments with low cellular density for further microbiological analyses. This work aimed at the evaluation of different matrices (arenite, shale and polyurethane foam) as support materials for microbial growth and biofilm formation in enrichments using a biodegraded petroleum sample as inoculum in sulfate reducing condition. Subsequent microbial diversity characterization was carried out using Scanning Electronic Microscopy (SEM), Denaturing Gradient Gel Electrophoresis (DGGE) and 16S rRNA gene libraries in order to compare the microbial biomass yield, DNA recovery efficiency and diversity among the enrichments. The DNA from microbial communities in petroleum enrichments was purified according to a protocol established in this work and used for 16S rRNA amplification with bacterial generic primers. The PCR products were cloned, and positive clones were screened by Amplified Ribosomal DNA Restriction Analysis (ARDRA). Sequencing and phylogenetic analyses revealed that the bacterial community was mostly represented by members of the genera Petrotoga, Bacillus, Pseudomonas, Geobacillus and Rahnella. The use of different support materials in the enrichments yielded an increase in microbial biomass and biofilm formation, indicating that these materials may be employed for efficient biomass recovery from petroleum reservoir samples. Nonetheless, the most diverse microbiota were recovered from the biodegraded petroleum sample using polyurethane foam cubes as support material. PMID- 27282731 TI - Neuralgic amyotrophy is not the most common neurologic disorder of the shoulder: a 78-month prospective study of 60 neurologic shoulder patients in a specialist shoulder clinic. AB - BACKGROUND: Neuralgic amyotrophy (NA) was first described in 1948. Traditional literature describes a painful attack with sudden onset, followed by paresis, with varied outcomes. Recent studies have suggested NA is currently underdiagnosed. However, a large number of studies detailing NA originate from a small group of sources. Our study compared the onset, diagnosis, investigation, and treatment of all neurologic shoulder conditions to provide comparable data for these studies. METHODS: Data were collected from 60 patients (81.6% male; median age, 41.5 years) during a 78-month period. Patients with a diagnosis of a neurologic disorder of the shoulder with confirmatory electromyogram (EMG) studies were included. RESULTS: NA was diagnosed in 18 patients before the EMG investigation. Of the clinically diagnosed NA patients, only 5 (27.8%) had EMG findings supportive of NA. A further 5 patients with a clinical diagnosis other than NA were diagnosed with NA after EMG findings. Overall, 10 patients (16.6%) in our study were diagnosed with NA after EMG studies. Only 4 (40.0%) reported a sudden onset attack associated with NA. Supraspinatus and infraspinatus were involved in 9 patients (90.0%), suggesting a predictable distribution of muscle involvement. CONCLUSIONS: These results suggest that NA is overdiagnosed and does not warrant the increased attention suggested by recent articles. The current study also highlights a necessity to perform EMG investigations in all cases of suspected NA because the accuracy of the clinical assessment is poor. PMID- 27282732 TI - Stress radiography for clinical evaluation of anterior shoulder instability. AB - BACKGROUND: The purpose of this study was to examine the validity of stress radiography using the Telos GA-IIE as a clinical methodology to evaluate shoulder instability. METHODS: On 36 anterior shoulder dislocators and 23 uninjured volunteers, 4 types of stress radiographs were captured while applying 15 daN of force anteriorly (AER0 and AER60) and posteriorly (PER0 and PER60) at 2 different positions: (1) 90 degrees of abduction combined with 0 degrees external rotation and (2) 90 degrees of abduction combined with 60 degrees external rotation. The results of the anterior drawer test and of the same test under anesthesia were correlated. RESULTS: AER0 and AER60 from the affected shoulder revealed significantly larger displacement than on the normal side (P < .05), and all 4 radiographs from the affected joints demonstrated significantly larger displacement (P < .05) than in the volunteers. Among the 4 types of radiographs, AER0 and AER60 showed significantly higher displacement in the patients (P < .001), whereas there were no differences in the volunteers (P = .167). The results of the anterior drawer test positively correlated to AER60 (Pearson correlation coefficient [PCC] = 0.453; P = .005) and AER0 (PCC = 0.529; P = .001), and those of examination under anesthesia weakly correlated to AER60 (PCC = 0.287; P = .264) but highly correlated to AER0 (PCC = 0.695; P = .002). CONCLUSION: Stress radiographs on the affected shoulder frequently correlated with physical examinations, and the displacement of >3 mm on AER0 suggests anterior instability. PMID- 27282733 TI - Accuracy of sagittal oblique view in preoperative indirect magnetic resonance arthrography for diagnosis of tears involving the upper third of the subscapularis tendon. AB - BACKGROUND: The purpose of this study was to investigate the accuracy of sagittal oblique view (SOV) magnetic resonance imaging grading for tears involving the upper third of the subscapularis tendons in correlation with arthroscopic findings. We also propose a schematic classification in the SOV for upper-third subscapularis tears. METHODS: The study analyzed 364 patients with an average age of 56.0 years. All patients underwent indirect magnetic resonance arthrography (MRA) before surgery. A slightly different magnetic resonance grading was introduced with SOV by musculoskeletal radiologists (Y.C.Y. and J.Y.Y.) and an orthopedic shoulder surgeon (H.Y.R.) who had no information about the clinical data. Subscapularis tendon tear classifications were all prospectively analyzed. Magnetic resonance grading was compared with the arthroscopic findings. RESULTS: The sensitivity, specificity, and accuracy of subscapularis tendon tear detection were 0.72, 0.77, and 0.75, respectively, for the radiologists. For the orthopedic surgeon, the corresponding values were 0.73, 0.83, and 0.79, respectively. The kappa coefficients for interobserver agreement comparing magnetic resonance grade of the musculoskeletal radiologists with the arthroscopic grading showed fair values (kappa value, 0.301). Interobserver agreement between the magnetic resonance grade of the orthopedic surgeon and arthroscopic grades was fair (kappa value, 0.377). Interobserver agreement between the musculoskeletal radiologists and the orthopedic surgeon was moderate (kappa value, 0.591). CONCLUSIONS: The accuracy of SOV indirect MRA for detecting tears was 0.75 to 0.79. Although the correlation between magnetic resonance and arthroscopic grading was only fair, for most of the magnetic resonancegrading on SOV, the first facet view showed similar results compared with arthroscopy. The accuracy of determining whether subscapularis repair is indicated was 0.82 to 0.83 with SOV indirect MRA. PMID- 27282734 TI - Partial rotator cuff repair and biceps tenotomy for the treatment of patients with massive cuff tears and retained overhead elevation: midterm outcomes with a minimum 5 years of follow-up. AB - BACKGROUND: A subset of patients with massive irreparable rotator cuff tears present with retained overhead elevation and pain as their primary complaint. Our aim was to evaluate the outcomes of partial arthroscopic rotator cuff repair with biceps tenotomy and to report the failure rate of this procedure for patients with >5 years of follow-up. METHODS: Thirty-four patients underwent partial rotator cuff repair and biceps tenotomy for treatment of a massive rotator cuff tear. Patients had preoperative active forward elevation >120 degrees and no radiographic evidence of glenohumeral arthritis. Patients were followed up clinically and radiographically, and 28 patients had a minimum of 5 years of follow-up. Failure was defined as an American Shoulder and Elbow Surgeons score of <70, loss of active elevation >90 degrees , or revision to reverse shoulder arthroplasty during the study period. RESULTS: Patients demonstrated improvements in average preoperative to postoperative American Shoulder and Elbow Surgeons scores (46.6 to 79.3 [P < .001]) and Simple Shoulder Test scores (5.7 to 9.1 [P < .001]) along with decrease in visual analog scale for pain scores (6.9 to 1.9 [P < .001]). No significant change in forward elevation (168 degrees to 154 degrees [P = .07]), external rotation (38 degrees to 39 degrees [P = 1.0]), or internal rotation (84% to 80% [P = 1.0]) was identified; 36% of patients had progression of the Hamada stage. The failure rate was 29%; 75% of patients were satisfied with their index procedure. CONCLUSION: Partial rotator cuff repair and biceps tenotomy for patients with massive irreparable rotator cuff tears with retained overhead elevation and pain as the primary complaint produced reasonable outcomes at midterm follow-up of at least 5 years. PMID- 27282735 TI - What factors are predictors of emotional health in patients with full-thickness rotator cuff tears? AB - BACKGROUND: The importance of emotional and psychological factors in treatment of patients with rotator cuff disease has been recently emphasized. Our goal was to establish factors most predictive of poor emotional health in patients with full thickness rotator cuff tears (FTRCTs). METHODS: In 2007, we began to prospectively collect data on patients with symptomatic, atraumatic FTRCTs. All patients completed a questionnaire collecting data on demographics, symptom characteristics, comorbidities, willingness to undergo surgery, and patient related outcomes (12-Item Short Form Health Survey, American Shoulder and Elbow Surgeons score, Western Ontario Rotator Cuff Index [WORC], Single Assessment Numeric Evaluation score, Shoulder Activity Scale). Physicians recorded physical examination and imaging data. To evaluate the predictors of lower WORC emotion scores, a linear multiple regression model was fit. RESULTS: Baseline data for 452 patients were used for analysis. In patients with symptomatic FTRCTs, the factors most predictive of worse WORC emotion scores were higher levels of pain (interquartile range odds ratio, -18.9; 95% confidence interval, -20.2 to -11.6; P < .0001) and lower Single Assessment Numeric Evaluation scores (rating of percentage normal that patients perceive their shoulder to be; interquartile range odds ratio, 6.2; 95% confidence interval, 2.5-9.95; P = .0012). Higher education (P = .006) and unemployment status (P = .0025) were associated with higher WORC emotion scores. CONCLUSIONS: Education level, employment status, pain levels, and patient perception of percentage of shoulder normalcy were most predictive of emotional health in patients with FTRCTs. Structural data, such astendon tear size, were not. Those with poor emotional health may perceive their shoulder to be worse than others and experience more pain. This may allow us to better optimize patient outcomes with nonoperative and operative treatment of rotator cuff tears. PMID- 27282736 TI - The yield of subsequent radiographs during nonoperative treatment of radial head and neck fractures. AB - OBJECTIVES: After diagnosis of an isolated radial head or neck fracture and selection of nonoperative treatment, the value of subsequent radiographs is uncertain. This study tested the null hypothesis that there are no patient, surgeon, or injury factors associated with alteration in patient management based on subsequent radiographs. Secondarily, we tested the null hypothesis that the use of subsequent radiographs is not associated with patient, surgeon, and fracture characteristics. METHODS: We identified 415 adult patients with nonoperative treatment for isolated Broberg and Morrey modified Mason type 1 or 2 fractures at a large urban hospital system during years 2013 and 2014. Patient demographics, fracture characteristics, provider characteristics, and treatment details were obtained from a hospital database. Bivariate analysis and multivariable logistic regression modeling were performed. RESULTS: One of 255 patients with 262 fractures that had subsequent radiographs (0.4%) was offered surgery but declined. In multivariable analysis, displaced fractures were more likely to have subsequent radiographs, but surgeon-to-surgeon variation was a far more influential factor. CONCLUSIONS: Radiographs subsequent to diagnosis do not alter treatment of radial head fractures with no associated ligament injuries or fractures. The substantial surgeon-to-surgeon variation in the use of subsequent radiographs suggests that this may be a good focus for quality improvement initiatives. PMID- 27282737 TI - Importance of the posterior bundle of the medial ulnar collateral ligament. AB - BACKGROUND: There has been a renewed interest in the pathomechanics of elbow dislocation, with recent literature having suggested that the medial ulnar collateral ligament is more often disrupted in dislocations than the lateral ligamentous complex. The purpose of this serial sectioning study was to determine the influence of the posterior bundle of the medial ulnar collateral ligament (pMUCL) as a stabilizer against elbow dislocation. METHODS: An elbow dislocation was simulated in 5 cadaveric elbows by mechanically applying an external rotation moment and valgus force. Medial ulnohumeral joint gapping was measured at 30 degrees , 60 degrees , and 90 degrees of flexion in an intact elbow after sectioning of the medial collateral ligament's anterior bundle (aMUCL) and then after sectioning of the pMUCL as well. RESULTS: After sectioning of the aMUCL, the pMUCL was able to stabilize the joint against dislocation. After aMUCL sectioning, the proximal joint space significantly increased by 4.2 +/- 0.6 mm at 30 degrees of flexion and 2.6 +/- 0.3 mm at 60 degrees of flexion, although it did not dislocate. The gapping increase of 0.9 +/- 0.6 at 90 degrees of flexion did not reach significance. After sectioning of the pMUCL (after having already sectioned the aMUCL), all of the specimens frankly dislocated at all flexion angles. CONCLUSIONS: An intact pMUCL can prevent elbow dislocation and limited joint subluxation to within 6.6 mm. Our findings indicate that repair or reconstruction may be warranted in certain circumstances (ie, residual instability after operative management of a terrible triad injury or after aMUCL reconstruction). PMID- 27282738 TI - A modification to the Walch classification of the glenoid in primary glenohumeral osteoarthritis using three-dimensional imaging. AB - BACKGROUND: Since Walch and colleagues originally classified glenoid morphology in the setting of glenohumeral osteoarthritis, several authors have reported varying levels of interobserver and intraobserver reliability. We propose several modifications to the Walch classification that we hypothesize will increase interobserver and intraobserver reliability. METHODS: We propose the addition of the B3 and D glenoids and a more precise definition of the A2 glenoid. The B3 glenoid is monoconcave and worn preferentially in its posterior aspect, leading to pathologic retroversion of at least 15 degrees or subluxation of 70%, or both. The D glenoid is defined by glenoid anteversion or anterior humeral head subluxation. The A2 glenoid has a line connecting the anterior and posterior native glenoid rims that transects the humeral head. Using 3-dimensional computed tomography glenoid reconstructions, 3 evaluators used the original Walch classification and the modified Walch classification to classify 129 nonconsecutive glenoids on 4 separate occasions. Reliabilities were assessed by calculating kappa coefficients. RESULTS: Interobserver reliabilities improved from an average of 0.391 (indicating fair agreement) using the original classification to an average of 0.703 (substantial agreement) using the modified classification. Intraobserver reliabilities improved from an average of 0.605 (moderate agreement) to an average of 0.882 (nearly perfect agreement). CONCLUSION: When 3-dimensional glenoid reconstructions and the modified Walch classification described herein are used, improved interobserver and intraobserver reliabilities are obtained. PMID- 27282739 TI - Outpatient total shoulder arthroplasty: a population-based study comparing adverse event and readmission rates to inpatient total shoulder arthroplasty. AB - BACKGROUND: The rate of total shoulder arthroplasty (TSA) is rising, which has an impact on health care expenditure. One avenue to mitigate cost is outpatient TSA. There are currently no published reports of this practice. In this study, we determine the 30-day adverse event and readmission rates after outpatient TSA and compare these rates with inpatient TSA. METHODS: A retrospective cohort study using a population database in the United States was undertaken. Patients who underwent primary TSA between 2005 and 2014 were identified and divided into 2 cohorts based on length of stay (LOS): outpatient TSA (LOS 0 days) and inpatient TSA (LOS >0 days). Patient and procedure characteristics were collected. The 30 day adverse event and readmission rates were calculated for each cohort. A multivariate logistic regression determined if the odds of an adverse event or readmission were significantly different between the inpatient and outpatient TSA cohorts. RESULTS: Overall, 7197 patients in this database underwent TSA between 2005 and 2014, of which 173 patients (2.4%) underwent outpatient TSA. The 30-day adverse event rate in the outpatient and inpatient TSA cohorts was 2.31% and 7.89%, respectively. The 30-day readmission rate in the outpatient and inpatient TSA cohorts was 1.74% and 2.93%, respectively. In the multivariate logistic regression, the odds of an adverse event or readmission were not significantly different (odds ratio of 0.4 [P = .077] and odds ratio of 0.7 [P = .623], respectively). CONCLUSION: There are no significant differences in the 30-day adverse event and readmission rates between outpatient and inpatient TSA. In the appropriately selected patient, outpatient TSA is safe and cost-effective. PMID- 27282741 TI - New indolizine-chalcones as potent inhibitors of human farnesyltransferase: Design, synthesis and biological evaluation. AB - A new family of indolizine-chalcones was designed, synthesized and screened for the inhibitory potential on human farnesyltransferase in vitro to identify potent antitumor agents. The most active compound was phenothiazine 2a, exhibiting an IC50 value in the low nanomolar range, similar to that of known FTI-276, highly potent farnesyltransferase inhibitor. The newly synthesized indolizine-chalcones 2a-d constitute the most efficient inhibitors of farnesyltransferase bearing a phenothiazine unit known to date. PMID- 27282740 TI - Cell-death-inducing DFFA-like Effector B Contributes to the Assembly of Hepatitis C Virus (HCV) Particles and Interacts with HCV NS5A. AB - Hepatitis C virus (HCV) uses components of the very-low-density lipoprotein (VLDL) pathway for assembly/release. We previously reported that hepatocyte nuclear factor 4alpha (HNF4alpha) participates in HCV assembly/release through downstream factors those participate in VLDL assembly/secretion. Cell-death inducing DFFA-like effector B (CIDEB) is an important regulator of the VLDL pathway. CIDEB is required for entry of HCV particles from cell culture (HCVcc), but the effects of CIDEB on the post-entry steps of the HCV lifecycle are unclear. In the present study, we determined that CIDEB is required for HCV assembly in addition to HCVcc entry. Furthermore, CIDEB interacts with the HCV NS5A protein, and the N terminus of CIDEB and the domain I of NS5A are involved in this interaction. Moreover, CIDEB silencing impairs the association of apolipoprotein E (ApoE) with HCV particles. Interestingly, CIDEB is also required for the post-entry stages of the dengue virus (DENV) life cycle. Collectively, these results indicate that CIDEB is a new host factor that is involved in HCV assembly, presumably by interacting with viral protein, providing new insight into the exploitation of the VLDL regulator CIDEB by HCV. PMID- 27282742 TI - Alkyl substituted aminal derivatives of HCV NS5A inhibitor MK-8742. AB - HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein we describe our continued research efforts around the alkyl "Z group" modification of the tetracyclic indole-based NS5A inhibitor MK-8742, which led to the discovery of a series of potent NS5A inhibitors. Compounds 10 and 19 are of particular interests since they are as potent as our previous leads and have much improved rat pharmacokinetic profiles. PMID- 27282745 TI - Corrigendum. PMID- 27282743 TI - Discovery of potent macrocyclic HCV NS5A inhibitors. AB - HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection. Merck's effort in this area identified MK-4882 and MK-8325 as early development leads. Herein, we describe the discovery of potent macrocyclic NS5A inhibitors bearing the MK-8325 or MK 4882 core structure. PMID- 27282744 TI - Default Network and Aging: Beyond the Task-Negative Perspective. AB - During cognitive tasks requiring externally directed attention, activation in the default-network (DN) typically decreases below baseline levels ('deactivation'). Healthy aging is associated with reduced deactivation, which is usually attributed to a failure to suppress DN processes. Recent evidence instead suggests that older adults may be more reliant on DN than young adults when performing these tasks. PMID- 27282746 TI - Delusional Infestation: State of the Art. AB - Patients with a delusional infestation (DI) have an overwhelming conviction that they are being infested with (non) pathogens without any medical proof. The patients need a systematic psychiatric and dermatological evaluation to assess any possible underlying cause that could be treated. Because they avoid psychiatrists, a close collaboration of dermatologists and psychiatrists, who examine the patient together, seems to be a promising solution. It helps to start a trustful doctor-patient relationship and motivates the patient for psychiatric treatment. We here review diagnostic criteria, classification of symptoms, pathophysiology and treatment options of DI. Antipsychotic medication is the treatment of choice when any other underlying cause or disorder is excluded. Further research is needed to assess the pathophysiology, and other treatment options for patients with DI. PMID- 27282747 TI - Recent advances in the preparation and application of monolithic capillary columns in separation science. AB - Novel column technologies involving various materials and efficient reactions have been investigated for the fabrication of monolithic capillary columns in the field of analytical chemistry. In addition to the development of these miniaturized systems, a variety of microscale separation applications have achieved noteworthy results, providing a stepping stone for new types of chromatographic columns with improved efficiency and selectivity. Three novel strategies for the preparation of capillary monoliths, including ionic liquid based approaches, nanoparticle-based approaches and "click chemistry", are highlighted in this review. Furthermore, we present the employment of state-of the-art capillary monolithic stationary phases for enantioseparation, solid-phase microextraction, mixed-mode separation and immobilized enzyme reactors. The review concludes with recommendations for future studies and improvements in this field of research. PMID- 27282748 TI - Carbon dots with strong excitation-dependent fluorescence changes towards pH. Application as nanosensors for a broad range of pH. AB - In this study, preparation of novel pH-sensitive N-doped carbon dots (NCDs) using glucose and urea is reported. The prepared NCDs present strong excitation dependent fluorescence changes towards the pH that is a new behavior from these nanomaterials. By taking advantage of this unique behavior, two separated ratiometric pH sensors using emission spectra of the NCDs for both acidic (pH 2.0 to 8.0) and basic (pH 7.0 to 14.0) ranges of pH are constructed. Additionally, by considering the entire Excitation-Emission Matrix (EEM) of NCDs as analytical signal and using a suitable multivariate calibration method, a broad range of pH from 2.0 to 14.0 was well calibrated. The multivariate calibration method was independent from the concentration of NCDs and resulted in a very low average prediction error of 0.067 pH units. No changes in the predicted pH under UV irradiation (for 3 h) and at high ionic strength (up to 2 M NaCl) indicated the high stability of this pH nanosensor. The practicality of this pH nanosensor for pH determination in real water samples was validated with good accuracy and repeatability. PMID- 27282749 TI - Hybrid approach combining chemometrics and likelihood ratio framework for reporting the evidential value of spectra. AB - Many chemometric tools are invaluable and have proven effective in data mining and substantial dimensionality reduction of highly multivariate data. This becomes vital for interpreting various physicochemical data due to rapid development of advanced analytical techniques, delivering much information in a single measurement run. This concerns especially spectra, which are frequently used as the subject of comparative analysis in e.g. forensic sciences. In the presented study the microtraces collected from the scenarios of hit-and-run accidents were analysed. Plastic containers and automotive plastics (e.g. bumpers, headlamp lenses) were subjected to Fourier transform infrared spectrometry and car paints were analysed using Raman spectroscopy. In the forensic context analytical results must be interpreted and reported according to the standards of the interpretation schemes acknowledged in forensic sciences using the likelihood ratio approach. However, for proper construction of LR models for highly multivariate data, such as spectra, chemometric tools must be employed for substantial data compression. Conversion from classical feature representation to distance representation was proposed for revealing hidden data peculiarities and linear discriminant analysis was further applied for minimising the within-sample variability while maximising the between-sample variability. Both techniques enabled substantial reduction of data dimensionality. Univariate and multivariate likelihood ratio models were proposed for such data. It was shown that the combination of chemometric tools and the likelihood ratio approach is capable of solving the comparison problem of highly multivariate and correlated data after proper extraction of the most relevant features and variance information hidden in the data structure. PMID- 27282750 TI - X-ray photoelectron spectroscopic and electrochemical impedance spectroscopic analysis of RuO2-Ta2O5 thick film pH sensors. AB - The paper reports on investigation of the pH sensing mechanism of thick film RuO2 Ta2O5 sensors by using X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). Interdigitated conductimetric pH sensors were screen printed on alumina substrates. The microstructure and elemental composition of the films were examined by scanning electron microscopy and energy dispersive spectroscopy. The XPS studies revealed the presence of Ru ions at different oxidation states and the surface hydroxylation of the sensing layer increasing with increasing pH. The EIS analysis carried out in the frequency range 10 Hz-2 MHz showed that the electrical parameters of the sensitive electrodes in the low frequency range were distinctly dependent on pH. The charge transfer and ionic exchange occurring at metal oxide-solution interface were indicated as processes responsible for the sensing mechanism of thick film RuO2 Ta2O5 pH sensors. PMID- 27282751 TI - Carbonaceous nanomaterials immobilised mixed matrix membrane microextraction for the determination of polycyclic aromatic hydrocarbons in sewage pond water samples. AB - In this study, the potential for carbonaceous nanomaterials to be used as adsorbents for the mixed matrix membrane (MMM) microextraction and preconcentration of organic pollutants was demonstrated. For this method, multiwall carbon nanotubes (MWCNT) and single layer graphene (SLG) nanoparticles were individually incorporated through dispersion in a cellulose triacetate (CTA) polymer matrix to form a MWCNT-MMM and SLG-MMM, respectively. The prepared membranes were evaluated for the extraction of selected polycyclic aromatic hydrocarbons (PAHs) present in sewage pond water samples. The extraction was performed by dipping a small piece of membrane (7 mm * 7 mm) in a stirred 7.5 mL sample solution to initiate the analyte adsorption. This step was followed by an analyte desorption into 60 MUL of methanol prior to high performance liquid chromatography (HPLC) analysis. When the optimum SLG-MMM microextraction technique was applied to spiked sewage pond water samples, the detection limit of the method for the PAHs were in the range of 0.02-0.09 ng/mL, with relative standard deviations of between 1.4% and 7.8%. Enrichment factors of 54-100 were achieved with relative recoveries of 99%-101%. A comparison was also made between the proposed approach and standard solid phase extraction using polymeric bonded octadecyl (C18) cartridges. PMID- 27282752 TI - Low cost and compact analytical microsystem for carbon dioxide determination in production processes of wine and beer. AB - The design, construction and evaluation of a low cost, cyclic olefin copolymer (COC)-based continuous flow microanalyzer, with optical detection, to monitor carbon dioxide in bottled wines and beers as well as in fermentation processes, is presented. The microsystem, constructed by computer numerically controlled (CNC) micromilling and using a multilayer approach, integrates microfluidics, gas diffusion module and an optical flow-cell in a single polymeric substrate. Its size is slightly bigger than a credit card, exactly 45 * 60 * 4 mm in the microfluidic and diffusion module zone and 22.5 * 40 * 3 mm in the flow-cell zone. The gas-diffusion module is based on a hydrophobic polyvinylidene fluoride (PVDF) membrane, which allows the transfer of the carbon dioxide present in the sample to a bromothymol blue (BTB) pH-sensitive acceptor solution, where the color change is measured optically. The detection system consisted of a LED with an emission peak at 607 nm and a photodiode integrated in a printed circuit board (PCB). The obtained analytical features after the optimization of the microfluidic platform and hydrodynamic variables are a linear range from 255 to 10000 mg L(-1) of CO2 and a detection limit of 83 mg L(-1) with a sampling rate of 30 samples h(-1). PMID- 27282754 TI - Transforming the Landscape of Caregiving. PMID- 27282753 TI - Joint-specific DNA methylation and transcriptome signatures in rheumatoid arthritis identify distinct pathogenic processes. AB - Stratifying patients on the basis of molecular signatures could facilitate development of therapeutics that target pathways specific to a particular disease or tissue location. Previous studies suggest that pathogenesis of rheumatoid arthritis (RA) is similar in all affected joints. Here we show that distinct DNA methylation and transcriptome signatures not only discriminate RA fibroblast-like synoviocytes (FLS) from osteoarthritis FLS, but also distinguish RA FLS isolated from knees and hips. Using genome-wide methods, we show differences between RA knee and hip FLS in the methylation of genes encoding biological pathways, such as IL-6 signalling via JAK-STAT pathway. Furthermore, differentially expressed genes are identified between knee and hip FLS using RNA-sequencing. Double evidenced genes that are both differentially methylated and expressed include multiple HOX genes. Joint-specific DNA signatures suggest that RA disease mechanisms might vary from joint to joint, thus potentially explaining some of the diversity of drug responses in RA patients. PMID- 27282755 TI - Primacy of lowered baseline glomerular filtration rate as a risk for incident chronic kidney disease: A longitudinal study in Japanese subjects. AB - AIM: Risk profile for incident chronic kidney disease (CKD) in Japanese subjects has not been established. Our aim was to identify risk factors for CKD in Japanese. METHODS: Consecutive 171 536 health examinees (median age 49 years and estimated glomerular filtration rate (eGFR) 78.2 mL/min per 1.73 m2 ) without CKD were re-examined after a median period of 6.2 years. Results of Cox proportional hazards models in randomly assigned two thirds (Derivation cohort) were verified in the rest (Validation cohort). CKD was defined as eGFR <60 mL/min per 1.73 m2 or positive dipstick proteinuria. RESULTS: In the Derivation cohort, CKD developed in 1002 (5.8%) subjects. Seven variables such as lower eGFR, male gender, higher uric acid concentration, lower red cell count and higher age and systolic blood pressure were identified as significant risks for CKD, with lowered eGFR being an overwhelmingly strong risk: adjusted hazard ratio for those with the baseline eGFR <70 mL/min per 1.73 m2 was as high as 90.1. Performance of prediction of CKD by the probability on the basis of the seven risk factors combined was only marginally preferable to eGFR alone. The area under the receiver operating characteristic curve (95% CI) for the prediction was 0.846 (0.826-0.864) and 0.822 (0.802-0.840) (P < 0.01), the kappa statistic was 0.263 and 0.250 (n.s.), and the mean absolute difference between "predicted probability" and "observed" CKD was 1.4% and 1.9% (P = 0.14) by the combined model and eGFR alone, respectively. CONCLUSION: Seven risk factors for incident CKD were identified in Japanese health examinees. However, lowered baseline eGFR outweighed other risks to the degree that eGFR alone was suffice for CKD prediction. PMID- 27282756 TI - Comparing Laparoscopic to Endoscopic Resections for Early Gastric Cancer in a High Volume North American Center. AB - Endoscopic submucosal dissection as an organ sparing option for early gastric cancer is becoming increasingly accepted as an alternative to laparoscopic gastrectomy. Given the very limited North American data, we sought to compare outcomes between endoscopic and laparoscopic resection of gastric malignant and premalignant tumors. Patients undergoing laparoscopic gastrectomy or endoscopic submucosal dissection from 2007 to 2014 for adenocarcinoma or dysplasia at the McGill University Health Center were identified from a prospectively collected database and dichotomized according to the surgical approach. Patient demographics, tumor characteristics, stage, oncologic outcome, length of stay, and postoperative complications were recorded. Of 155 patients with gastric cancer identified, 67 were treated by laparoscopic gastrectomy (n = 37) or endoscopic submucosal dissection (ESD) (n = 30). There were significantly more invasive lesions in the laparoscopic group and patients subject to ESD harbored more T1 lesions. No significant difference in the rate of R0 resection or overall complications was observed between the groups. Accordingly, length of stay was significantly shorter in the ESD group. There were no significant differences in terms of overall and disease-free survival. In selected patients, ESD is associated with improved short-term outcomes and provides an appropriate oncologic resection option in a North American patient cohort. PMID- 27282757 TI - Erratum to: Deconstructing the "July Effect" in Operative Outcomes: A National Study. PMID- 27282758 TI - Sex Differences in the Prevalence of Oppositional Defiant Disorder During Middle Childhood: a Meta-Analysis. AB - This review provides a meta-analysed male:female prevalence ratio of oppositional defiant disorder (ODD) during middle childhood in non-referred children. It also analyses sex differences in prevalence across cultures and over time. A systematic search for studies via the following sources was conducted: PsycInfo, Web of Knowledge, Medline Complete, Scopus, EMBASE, InfoRMIT, Psychological and Behavioural Sciences Collection, Cochrane Library, PubMed and ProQuest Health. The studies presented in two previous systematic reviews were also added to the search results. Inclusion/exclusion criteria were then applied and final studies were appraised for their methodological quality. Nineteen independent effect sizes met full inclusion criteria (aggregated sample N = 44,107). Overall, the prevalence of ODD was significantly higher in boys than girls (RR = 1.59, 95 % CI [1.36, 1.86], p < 0.001), with the male:female prevalence ratio found to be 1.59:1. Sex differences in prevalence were significant in Western (RR = 1.80, 95 % CI [1.55, 2.10], p < 0.001) but not non-Western cultures (RR = 1.08, 95 % CI [0.76-1.53], p > 0.05). Sex differences in prevalence were significant in studies published prior to and post the year 2000 (RR = 1.57, 95 % CI [1.22, 2.02], p < 0.001; RR = 1.64, 95 % CI [1.35, 2.00], p < 0.001), and were consistent between these two periods (Q, 1 = 0.36, p = > 0.05). The sex differences in ODD prevalence are discussed within the context of (i) predominant theories of sex differences in externalising behaviours, and (ii) departure from the sex differences pattern found for other disruptive behavioural disorders. PMID- 27282759 TI - Linking Social Anxiety with Social Competence in Early Adolescence: Physiological and Coping Moderators. AB - Despite relatively universal feelings of discomfort in social situations, there is considerable evidence for diversity in the social behaviors and peer experiences of socially anxious youth. However, to date, very little research has been conducted with the aim of identifying factors that differentiate socially anxious youth who are more socially competent from those who are less socially competent. The present study addresses this gap in the literature by examining whether physiological and cognitive coping responses to social stress moderate the association between social anxiety and social competence. Participants were a community sample of 123 fifth and sixth graders (Mage = 12.03). Social anxiety was measured globally and in the context of a lab-based peer evaluation situation, and social competence was assessed via teacher-reports. Physiological (i.e., skin conductance level reactivity, SCLR, and respiratory sinus arrhythmia reactivity, RSAR) and coping (i.e., disengaged) responses to social stressors were also assessed. Results indicated that SCLR and disengaged coping with peer victimization moderated associations linking global and context-specific social anxiety with social competence, such that social anxiety was associated with lower social competence at lower levels of SCLR and higher levels of disengaged coping with peer victimization. Thus, whether socially anxious preadolescents exhibit more or less competent social behavior may depend, in part, on how they respond to peer-evaluative stress. Inflexible physiological responses and disengaged coping responses may undermine social competence, whereas engaged responses may counteract socially anxious preadolescents' tendency to withdraw from social interactions or focus primarily on threat cues. PMID- 27282760 TI - [Ewing's sarcoma, fibrogenic tumors, giant cell tumor, hemangioma of bone : Radiology and pathology]. AB - Radiological imaging only reflects the anatomy and its pathological abnormalities. Therefore, the radiologist should be able to recognize the basic features of the pathological anatomy of bone tumors. This can only be learned working closely with a pathologist who is experienced in this field. On the other hand, the pathologist needs from the radiologist their diagnostic assessment with information on size, location, aggressiveness and the existence of a bone tumor's matrix, of the whole lesion, because he usually only receives a small part for examination in the form of a biopsy. In this article, the features and fundamentals (standards) of radiological-pathological cooperation as the mainstay for a precise diagnosis in bone tumors are outlined. The radiological appearance and the histopathological features behind it are presented for Ewing's sarcoma, fibrogenic tumors, giant cell tumor, and hemangioma of the bone. PMID- 27282761 TI - [Not Available]. PMID- 27282762 TI - Erratum. PMID- 27282763 TI - Comparison of Outcomes after Device Closure with Transseptal Puncture and Standard Technique in Patients with Patent Foramen Ovale and Ischemic Events. AB - OBJECTIVES: The purpose of this study was to compare the effectiveness of device closure with the transseptal puncture and standard technique in patients with patent foramen ovale (PFO) and ischemic events. METHODS: Eighty-two consecutive patients (men: 60 patients, mean age: 45.2 years) who underwent PFO closure with the Amplatzer PFO Occluder were enrolled. PFO closure with the transseptal puncture was performed in 22 patients (transseptal puncture technique, group I). In the remaining patients (n = 60), PFO closure was performed with the standard technique (group II). The co-primary end points were the incidence of significant residual shunt on follow-up transesophageal echocardiography (TEE) and a composite of death, stroke, transient ischemic attack (TIA), and peripheral embolism. RESULTS: Baseline characteristics were similar between the two groups. On TEE, despite similar grade of interatrial right-to-left shunt, shunt at rest/septal hypermobility was less common in group I than in group II (40.9% vs. 72.9%, P < 0.010). The device was successfully implanted in all patients. On follow-up TEE, significant residual shunt was more common in group I than in group II (28.6% vs. 4.3%, P = 0.021). In addition, composite of death, stroke, TIA, or peripheral embolism was more common in group I than in group II (13.6% vs. 0%, P = 0.017) during the follow-up period (mean 25.4 months). CONCLUSION: Compared to the standard technique, PFO closure with the transseptal puncture technique showed higher incidence of residual shunt and ischemic events. Therefore, this technique might be considered in only highly selected patients as the last option. PMID- 27282764 TI - [Formula: see text]Parent rating of executive function in fetal alcohol spectrum disorder: A review of the literature and new data on Aboriginal Canadian children. AB - Aboriginal children in Canada are at high risk of fetal alcohol spectrum disorder (FASD) but there is little research on the cognitive impact of prenatal alcohol exposure (PAE) in this population. This paper reviews the literature on parent report of executive functioning in children with FASD that used the Behavior Rating Inventory of Executive Function (BRIEF). New data on the BRIEF is then reported in a sample of 52 Aboriginal Canadian children with FASD for whom a primary caregiver completed the BRIEF. The children also completed a battery of neuropsychological tests. The results reveal mean scores in the impaired range for all three BRIEF index scores and seven of the eight scales, with the greatest difficulties found on the Working Memory, Inhibit and Shift scales. The majority of the children were reported as impaired on the index scores and scales, with Working Memory being most commonly impaired scale. On the performance-based tests, Trails B and Letter Fluency are most often reported as impaired, though the prevalence of impairment is greater for parent ratings than test performance. No gender difference is noted for the parent report, but the boys had slightly slower intellectual functioning and were more perseverative than the girls on testing. The presence of psychiatric comorbidity is unrelated to either BRIEF or test scores. These findings are generally consistent with prior studies indicating that parents observe considerable executive dysfunction in children with FASD, and that children with FASD may have more difficulty with executive functions in everyday life than is detected by laboratory-based tests alone. PMID- 27282765 TI - Platelets are versatile cells: New discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond. AB - Platelets are small anucleate blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. At the site of vascular injury, platelet adhesion, activation and aggregation constitute the first wave of hemostasis. Blood coagulation, which is initiated by the intrinsic or extrinsic coagulation cascades, is the second wave of hemostasis. Activated platelets can also provide negatively-charged surfaces that harbor coagulation factors and markedly potentiate cell-based thrombin generation. Recently, deposition of plasma fibronectin, and likely other plasma proteins, onto the injured vessel wall has been identified as a new "protein wave of hemostasis" that may occur even earlier than the first wave of hemostasis, platelet accumulation. Although no experimental evidence currently exists, it is conceivable that platelets may also contribute to this protein wave of hemostasis by releasing their granule fibronectin and other proteins that may facilitate fibronectin self- and non-self-assembly on the vessel wall. Thus, platelets may contribute to all three waves of hemostasis and are central players in this critical physiological process to prevent bleeding. Low platelet counts in blood caused by enhanced platelet clearance and/or impaired platelet production are usually associated with hemorrhage. Auto- and allo-immune thrombocytopenias such as idiopathic thrombocytopenic purpura and fetal and neonatal alloimmune thrombocytopenia may cause life-threatening bleeding such as intracranial hemorrhage. When triggered under pathological conditions such as rupture of an atherosclerotic plaque, excessive platelet activation and aggregation may result in thrombosis and vessel occlusion. This may lead to myocardial infarction or ischemic stroke, the major causes of mortality and morbidity worldwide. Platelets are also involved in deep vein thrombosis and thromboembolism, another leading cause of mortality. Although fibrinogen has been documented for more than half a century as essential for platelet aggregation, recent studies demonstrated that fibrinogen-independent platelet aggregation occurs in both gene deficient animals and human patients under physiological and pathological conditions (non-anti coagulated blood). This indicates that other unidentified platelet ligands may play important roles in thrombosis and might be novel antithrombotic targets. In addition to their critical roles in hemostasis and thrombosis, emerging evidence indicates that platelets are versatile cells involved in many other pathophysiological processes such as innate and adaptive immune responses, atherosclerosis, angiogenesis, lymphatic vessel development, liver regeneration and tumor metastasis. This review summarizes the current knowledge of platelet biology, highlights recent advances in the understanding of platelet production and clearance, molecular and cellular events of thrombosis and hemostasis, and introduces the emerging roles of platelets in the immune system, vascular biology and tumorigenesis. The clinical implications of these basic science and translational research findings will also be discussed. PMID- 27282766 TI - Potential forensic use of a 33 X-InDel panel in the Argentinean population. AB - Polymorphic genetic markers located on the X chromosome might become a complement in particular forensic identification when the biological kinship are deficient. We analyzed forensic statistical parameters of 33 X-chromosome InDel polymorphisms in a sample of 320 individuals from Argentina. The X-chromosome InDel polymorphism (X-InDel) panel was amplified in a single multiplex PCR reaction. Hardy-Weinberg Equilibrium was determined in the female cohort, whereas the male cohort was used to calculate linkage disequilibrium (LD) tested by an extension of Fisher's exact test, D', and Chi-square values. Regarding LD, 15 markers were organized and grouped into six blocks containing two or three linked loci each, namely block I (MID356-MID357), block II (MID448804-MID3703-MID218), block III (MID3705-MID3706-MID304737), block IV (MID197147-MID3754), block V (MID3664-MID284601-MID103547), and block VI (MID3763-MID3728). The haplotype diversity was higher than 0.99 in all cases. Blocks III and VI showed the highest match probability in the studied population, whereas block II showed the lowest. The accumulated power of discrimination was 99.9999991 % in women and 99.9992925 % in men. The mean exclusion chance in trios and duos were 99.9891736 and 99.6099391 %, respectively. Since 15 markers are associated as haplotypic blocks, for a conservative treatment of the data, statistical evaluation should consider their haplotypic frequencies and the remaining 18 markers can be evaluated as independent loci. PMID- 27282768 TI - Jeotgalicoccus schoeneichii sp. nov. isolated from exhaust air of a pig barn. AB - A Gram-staining-positive, non-motile, non-spore-forming, coccus (strain 140805 STR-02T) was isolated from exhaust air of a pig barn on Columbia Blood Agar Base (Oxoid) supplemented with 5 % defibrinated horse blood, Streptococcus selective supplement and 0.5 mg erythromycin l-1. The strains shared high 16S rRNA gene sequence similarity to Jeotgalicoccus pinnipedialis (98.6 %) but only a maximum of 94 % sequence similarity to all other species of the genus Jeotgalicoccus. DNA DNA hybridisation values between strain 140805-STR-02T and J. pinnipedialis CIP 107946T were 60.3 % (reciprocal, 51.2 %). The quinone system of 140805-STR-02T contained predominantly menaquinone MK-7 and minor amounts of MK-6. The polar lipid profile of strain 140805-STR-02T contained the major compounds diphosphatidylglycerol and phosphatidylglycerol and four unidentified lipids present in minor to moderate amounts. In the polyamine pattern spermidine and spermine were predominant. The fatty acid profile comprising iso-C15 : 0 and anteiso-C15 : 0 as major fatty acids, and was in congruence with those reported for other species of the genus Jeotgalicoccus and thus supported the affiliation of strain 140805-STR-02T to this genus. The results of physiological and biochemical tests allowed a clear phenotypic differentiation of strain 140805-STR 02T from the most closely related species. Strain 140805-STR-02T represents a novel species, for which the names Jeotgalicoccus schoeneichii sp. nov. is proposed, with the type strain 140805-STR-02T (=LMG 29445T=CCM 8667T). PMID- 27282767 TI - Adrenomedullin and endothelin-1 are associated with myocardial injury and death in septic shock patients. AB - BACKGROUND: Adrenomedullin and endothelin-1 are hormones with opposing effects on the cardiovascular system. Adrenomedullin acts as a vasodilator and seems to be important for the initiation and continuation of the hyperdynamic circulatory response in sepsis. Endothelin-1 is a vasoconstrictor and has been linked to decreased cardiac performance. Few studies have studied the relationship between adrenomedullin and endothelin-1, and morbidity and mortality in septic shock patients. High-sensitivity troponin T (hsTNT) is normally used to diagnose acute cardiac injury but is also prognostic for outcome in intensive care. We investigated the relationship between mid-regional pro-adrenomedullin (MR proADM), C-terminal pro-endothelin-1 (CT-proET-1), and myocardial injury, measured using transthoracic echocardiography and hsTNT in septic shock patients. We were also interested in the development of different biomarkers throughout the ICU stay, and how early measurements were related to mortality. Further, we assessed if a positive biomarker panel, consisting of MR-proADM, CT-proET-1, and hsTNT changed the odds for mortality. METHODS: A cohort of 53 consecutive patients with septic shock had their levels of MR-proADM, CT-proET-1, hsTNT, and left ventricular systolic functions prospectively measured over 7 days. The relationship between day 1 levels of MR-proADM/CT-proET-1 and myocardial injury was studied. We also investigated the relationship between biomarkers and early (7-day) and later (28-day) mortality. Likelihood ratios, and pretest and posttest odds for mortality were calculated. RESULTS: Levels of MR-proADM and CT-proET-1 were significantly higher among patients with myocardial injury and were correlated with left ventricular systolic dysfunction. MR-proADM and hsTNT were significantly higher among 7-day and 28-day non-survivors. CT-proET-1 was also significantly higher among 28-day but not 7-day non-survivors. A positive biomarker panel consisting of the three biomarkers increased the odds for mortality 13-fold to 20-fold. CONCLUSIONS: MR-proADM and CT-proET-1 are associated with myocardial injury. A biomarker panel combining MR-proADM, CT proET-1, and hsTNT increases the odds ratio for death, and may improve currently available scoring systems in critical care. PMID- 27282769 TI - Influence of school-related factors on smoking among Chilean adolescents: a cross sectional multilevel study. AB - BACKGROUND: Adolescent tobacco smoking is a major health concern in Chile. Schools may be able to influence adolescent behaviour regarding smoking; however, this topic has received limited research attention in Latin-American countries. Moreover, the prevalence of cigarette smoking varies between schools, and some of this variability may be explained by school factors. This article examines the inter-school variability in student smoking in a large sample of Chilean schools and identifies the school- and student-level characteristics associated with cigarette smoking. METHODS: This cross-sectional study used self-reported student level data from 45,273 students from 1462 schools and official data from these schools provided by the Chilean Ministry of Education (2007). Student smoking behaviour was used as an outcome, and individual-level and school-level features were used as explanatory variables. Logistic multilevel modelling was used to analyse the data. RESULTS: The mean prevalence of smoking in the 1462 schools was 39.9 %. The null model indicated that 8 % of the variance in smoking behaviour was explained by schools; and in the final model, controlled by individual- and school-level variables, the variance explained by schools dropped to 2.4 %. The main school-level variables explaining the school influence were school bonding, school truancy and school achievement. CONCLUSIONS: This is the first study to examine the extent to which student smoking varies between Chilean schools and to identify some of the school factors associated with this inter-school variability. Although most variation in smoking prevalence lies between students within schools, there is sufficient between-school variation to be of interest to educators and policy makers. PMID- 27282770 TI - Effects of BDNF-Transfected BMSCs on Neural Functional Recovery and Synaptophysin Expression in Rats with Cerebral Infarction. AB - The purpose of this study was to investigate the effects of brain-derived neurotrophic factor (BDNF)-transfected bone marrow mesenchymal stem cells (BMSCs) on neural functional recovery and synaptophysin expression in rats with cerebral infarction (CI). A total of 120 healthy Sprague Dawley rats were randomly divided into sham group, control group, and model group. Craniotomy was conducted and neurological function defect scoring was used to verify the model. BDNF containing recombinant plasmid was transfected into rat BMSCs, which was verified by flow cytometry and Western Blot. After injection of the transfected BMSCs, neural functional recovery of the CI rats and synaptophysin expression were measured. After the CI rat model was established, magnetic resonance (MR) imaging, 2, 3, 5- triphenyl tetrazolium chloride (TTC) staining, and the neurological function defect scoring determined the success of the model. CD34 ( ), CD45 (-), CD29 (+), and CD90 (+) cells detected showed that the obtained BMSCs have high purity. BDNF protein was highly expressed in the BMSCs successfully transfected with the recombinant plasmid. Balance beam walking score, rotating bar walking score, and screen test score were significantly lower, while synaptophysin expression was higher in the BDNF model group than those in the non BDNF model group and sham group with time extension. BDNF can increase synaptic plasticity and neurogenesis and have a promotional role in neural functional recovery and synaptophysin expression in rats with CI. BDNF-transfected BMSCs may therefore have better treatment efficacy for CI clinically. PMID- 27282771 TI - Prognostic Role of Body Mass Index in Advanced Small Bowel Adenocarcinoma Patients Receiving Palliative Chemotherapy. AB - As small bowel adenocarcinoma (SBA) is a rare cancer worldwide, prognostic factors have not been clearly defined. The purpose of this study is to assess the prognostic role of clinicopathologic features, including body mass index (BMI), in patients with advanced SBA. A total of 28 consecutive patients with advanced SBA treated with palliative chemotherapy were retrospectively enrolled and analyzed. Clinicopathologic features, progression-free survival (PFS), and overall survival (OS) were compared according to BMI level. Eighteen patients had BMI < 25 kg/m(2) (overweight/normal/underweight in Asian) and ten patients had BMI >= 25 kg/m(2) (obese in Asian). Baseline characteristics were similar regardless of patient's BMI. Compared to patients with BMI < 25 kg/m(2), patients with BMI >= 25 kg/m(2) had higher response rate to chemotherapy (40.0% vs. 0%, P = 0.010), longer OS (11.2 vs. 7.0 months, P = 0.018) and a tendency toward prolonged PFS (2.1 vs. 1.9 months, P = 0.085). Multivariate analysis revealed that BMI >= 25 kg/m(2) is an independent positive prognostic factor of OS (adjusted hazard ratio 0.35, P = 0.024). In conclusion, baseline BMI >= 25 kg/m(2) has a positive prognostic role in patients with advanced SBA. PMID- 27282772 TI - Mycorrhizal detection of native and non-native truffles in a historic arboretum and the discovery of a new North American species, Tuber arnoldianum sp. nov. AB - During a study comparing the ectomycorrhizal root communities in a native forest with those at the Arnold Arboretum in Massachusetts (USA), the European species Tuber borchii was detected on the roots of a native red oak in the arboretum over two successive years. Since T. borchii is an economically important edible truffle native to Europe, we conducted a search of other roots in the arboretum to determine the extent of colonization. We also wanted to determine whether other non-native Tuber species had been inadvertently introduced into this 140 year-old Arboretum because many trees were imported into the site with intact soil and roots prior to the 1921 USDA ban on these horticultural practices in the USA. While T. borchii was not found on other trees, seven other native and exotic Tuber species were detected. Among the North American Tuber species detected from ectomycorrhizae, we also collected ascomata of a previously unknown species described here as Tuber arnoldianum. This new species was found colonizing both native and non-native tree roots. Other ectomycorrhizal taxa that were detected included basidiomycetes in the genera Amanita, Russula, Tomentella, and ascomycetes belonging to Pachyphlodes, Helvella, Genea, and Trichophaea. We clarify the phylogenetic relationships of each of the Tuber species detected in this study, and we discuss their distribution on both native and non-native host trees. PMID- 27282773 TI - Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes. AB - Amide bond-forming reactions are of tremendous significance in synthetic chemistry. Methodological research has, in the past, focused on efficiency and selectivity, and these have reached impressive levels. However, the unacceptable amounts of waste produced have led the ACS GCI Roundtable to label 'amide bond formation avoiding poor atom economy' as the most pressing target for sustainable synthetic method development. In response to this acute demand, we herein disclose an efficient one-pot amide coupling protocol that is based on simple alkynes as coupling reagents: in the presence of a dichloro[(2,6,10-dodecatriene) 1,12-diyl]ruthenium catalyst, carboxylate salts of primary or secondary amines react with acetylene or ethoxyacetylene to vinyl ester intermediates, which undergo aminolysis to give the corresponding amides along only with volatile acetaldehyde or ethyl acetate, respectively. The new amide synthesis is broadly applicable to the synthesis of structurally diverse amides, including dipeptides. PMID- 27282774 TI - Age-related differences in the sonographic characteristics of endometriomas. AB - STUDY QUESTION: Do sonographic characteristics of ovarian endometriomas vary with age in premenopausal women? SUMMARY ANSWER: With increasing age, multilocular cysts and cysts with papillations and other solid components become more common whereas ground glass echogenicity of cyst fluid becomes less common. WHAT IS KNOWN ALREADY: Expectant or medical management of women with endometriomas is now accepted. Therefore, the accuracy of non-invasive diagnosis of these cysts is pivotal. A clinically relevant question is whether the sonographic characteristics of ovarian endometriomas are the same irrespective of the age of the woman. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of cross sectional data in the International Ovarian Tumor Analysis (IOTA) database. The database contains clinical and ultrasound information collected pre-operatively between 1999 and 2012 from 5914 patients with adnexal masses in 24 ultrasound centres in 10 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 1005 histologically confirmed endometriomas in adult premenopausal patients found in the database and these were used in our analysis. The following ultrasound variables (defined using IOTA terminology) were used to describe the ultrasound appearance of the endometriomas: tender mass at ultrasound, largest diameter of lesion, tumour type (unilocular, unilocular-solid, multilocular, multilocular solid, solid), echogenicity of cyst content, presence of papillations, number of papillations, height (mm) of largest papillation, presence and proportion of solid tissue and number of cyst locules, as well as vascularity in papillations and colour content of the tumour scan (colour score) on colour or power Doppler ultrasounds. Results are reported as median difference or odds ratio (OR) per 10 years increase in age. MAIN RESULTS AND THE ROLE OF CHANCE: Maximal lesion diameter did not vary substantially with age (+1.3 mm difference per 10 years increase in age, 95% confidence interval (CI) -1.4 to 4.0). Tender mass at scan was less common in the older the woman (OR 0.75, 95% CI 0.63-0.89), as were unilocular cysts relative to multilocular cysts (OR 0.70, 95% CI 0.57-0.85) and to lesions with solid components (OR 0.61, 95% CI 0.48-0.77), and ground glass echogenicity relative to homogeneous low-level echogenicity (OR 0.74, 95% CI 0.58 0.94) and other types of echogenicity of cyst contents (OR 0.64, 95% CI 0.50 0.81). Papillations were more common the older the woman (OR 1.65, 95% CI 1.24 2.21), but their height and vascularization showed no clear relation to age. LIMITATIONS, REASONS FOR CAUTION: It is a limitation that we have little clinical information on the women included, e.g. previous surgery or medical treatment for endometriosis. It is important to emphasize that we do not know the age of the endometrioma itself and that our study is not longitudinal and so does not describe changes in endometriomas over time. The differences in the ultrasound appearance of endometriomas between women of different ages might be explained by previous surgery or medical treatment and might not be an effect of age per se. WIDER IMPLICATIONS OF THE FINDINGS: Awareness of physicians that the ultrasound appearance of endometriomas differs between women of different ages may facilitate a correct diagnosis of endometrioma. STUDY FUNDING/COMPETING INTERESTS: This study was supported in part by the Regione Autonoma della Sardegna (project code CPR-24750). B.V.C., A.C. and D.T. are supported by the Fund for Scientific Research Flanders, Belgium (FWO). The authors declare that there is no conflict of interest. PMID- 27282775 TI - Women's adjustment trajectories during IVF and impact on mental health 11-17 years later. AB - STUDY QUESTION: Do patients present different adjustment trajectories during and after IVF treatment? SUMMARY ANSWER: Most women show resilient trajectories during and after IVF treatment but 37% show temporary or chronic maladjustment during IVF and 10% are maladjusted 11-17 years after treatment. WHAT IS KNOWN ALREADY: Research on patient psychosocial adjustment during treatment has contributed to identifying the most distressful stages of IVF treatment and profiling patients at risk for emotional maladjustment at these specific stages. This knowledge is currently driving the deliverance of psychosocial care at fertility clinics by tailoring it to patients' risk profiles and specific treatment stages. However, current care does not take into consideration how individuals adjust across the entire treatment pathway. This can be assessed by profiling individual adjustment trajectories. STUDY DESIGN, SIZE, DURATION: A longitudinal cohort study with five assessment moments that combines data from two different studies, the STRESSIVF and OMEGA projects. Participants enrolled in the STRESSIVF study (started IVF in 1998-2000) were assessed before and after the first IVF treatment cycle and 6 months and 2.5 years after the last IVF cycle. A subset participated in the OMEGA project (started IVF in 1995-2000) and reported on their mental health 11-17 years after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three hundred and forty-eight women participated in the STRESSIVF project and 108 of these in the OMEGA. Anxiety was measured with the State and Trait Anxiety Inventory, depression with the Beck Depression Inventory and mental health with the Mental Health Inventory. Latent class growth mixed modelling was carried out to identify distinct anxiety and depression trajectories over the four STRESSIVF study assessment moments. Multinominal logistic regressions were conducted to investigate predictors of trajectory membership, and stepwise linear regressions were performed to investigate if adjustment trajectories predicted mental health 11-17 years after IVF treatment. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 67 and 86% of women showed normal levels of anxiety and depression, respectively, throughout treatment (resilient trajectories), 24 and 33% experienced anxiety and depression only during treatment (recovery trajectories), 4.6 and 4.9% experienced anxiety and depression only after treatment (delayed trajectories), and 4.3% showed chronic anxiety (chronic trajectory, not identified for depression). Non-resilient trajectories were associated with unsuccessful treatment, marital dissatisfaction, lack of social support and negative infertility cognitions. One in 10 women had a delayed or chronic trajectory and these trajectories predicted serious mental health impairment 11-17 years after treatment. LIMITATIONS, REASONS FOR CAUTION: The study only focuses on women. In the OMEGA project adjustment was assessed using a mental health measure. Although we could investigate how trajectories predicted mental health, it would have been preferable to map anxiety and depression trajectories up to 11-17 years after treatment. Missing analysis showed selective dropout from the study but this was accounted for by using mixed models and imputation procedures. Finally, data on other life stressors were not collected; therefore any contribution from these events cannot be assessed. WIDER IMPLICATIONS OF THE FINDINGS: Fertility health care providers have been called upon considering their responsibility in supporting patients in the aftermath of treatment. Results show it is possible to profile different groups of at-risk women at the start of the treatment and tailor psychosocial support to risk profile to promote health adjustment during treatment and thereafter. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant from the Dutch Cancer Society (2006-3631) and the Praeventiefonds (28-3012). No competing interests exist. PMID- 27282776 TI - Enhancement by GOSPEL protein of GAPDH aggregation induced by nitric oxide donor and its inhibition by NAD(.). AB - Glyceraldehyde-3-phosphate dehydrogenase's (GAPDH's) competitor of Siah Protein Enhances Life (GOSPEL) is the protein that competes with Siah1 for binding to GAPDH under NO-induced stress conditions preventing Siah1-bound GAPDH nuclear translocation and subsequent apoptosis. Under these conditions, GAPDH may also form amyloid-like aggregates proposed to be involved in cell death. Here, we report the in vitro enhancement by GOSPEL of NO-induced GAPDH aggregation resulting in the formation GOSPEL-GAPDH co-aggregates with some amyloid-like properties. Our findings suggest a new function for GOSPEL, contrasting with its helpful role against the apoptotic nuclear translocation of GAPDH. NAD(+) inhibited both GAPDH aggregation and co-aggregation with GOSPEL, a hitherto undescribed effect of the coenzyme against the consequences of oxidative stress. PMID- 27282777 TI - Effect of cis-(Z)-flupentixol on DPPC membranes in the presence and absence of cholesterol. AB - Cis-(Z)-flupentixol dihydrochloride (FLU), a thioxanthene drug, is used in therapy of schizophrenia as well as in anxiolytic and depressive disorders. Since the action mechanism of FLU is not completely understood, the main objective of present study is to provide a detailed evaluation of flupentixol-phospholipid membrane interactions at molecular level. FLU-dipalmitoylphosphatidylcholine (DPPC) interactions in presence and absence of cholesterol (CHO) were investigated as a function of temperature. The changes in upper part of membrane were more pronounced than those in central part of membrane, as indicated by EPR and FTIR. FLU was proposed to incorporate into phospholipid membranes with its triple ring parallel to head group and its chain toward alkyl chain of phospholipids. According to DSC results, the incorporation of 10 mol% FLU into DPPC caused a shoulder in transition peak, suggesting the occurence of a phase separation, and formation of this new phase is still observable in presence of CHO. It is well known that, structure and dynamics of lipids have significant influence on the function of membrane bound proteins, and consecutively their actions. Based upon these, it was proposed that FLU may modify membrane associated receptors and transport proteins, which would form the basis of its clinical efficiency. PMID- 27282778 TI - Prospective longitudinal voxel-based morphometry study of major depressive disorder in young individuals at high familial risk. AB - BACKGROUND: Previous neuroimaging studies indicate abnormalities in cortico limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel based morphometry to examine the trajectory of these abnormalities during early stages of illness development. METHOD: Unaffected individuals (16-25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls ('low risk', n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures. RESULTS: Significant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline. CONCLUSIONS: These longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures. PMID- 27282779 TI - Structure of the host-recognition device of Staphylococcus aureus phage phi11. AB - Phages play key roles in the pathogenicity and adaptation of the human pathogen Staphylococcus aureus. However, little is known about the molecular recognition events that mediate phage adsorption to the surface of S. aureus. The lysogenic siphophage phi11 infects S. aureus SA113. It was shown previously that phi11 requires alpha- or beta-N-acetylglucosamine (GlcNAc) moieties on cell wall teichoic acid (WTA) for adsorption. Gp45 was identified as the receptor binding protein (RBP) involved in this process and GlcNAc residues on WTA were found to be the key component of the phi11 receptor. Here we report the crystal structure of the RBP of phi11, which assembles into a large, multidomain homotrimer. Each monomer contains a five-bladed propeller domain with a cavity that could accommodate a GlcNAc moiety. An electron microscopy reconstruction of the phi11 host adhesion component, the baseplate, reveals that six RBP trimers are assembled around the baseplate core. The Gp45 and baseplate structures provide insights into the overall organization and molecular recognition process of the phage phi11 tail. This assembly is conserved among most glycan-recognizing Siphoviridae, and the RBP orientation would allow host adhesion and infection without an activation step. PMID- 27282781 TI - Revealing the Origin of Fast Electron Transfer in TiO2-Based Dye-Sensitized Solar Cells. AB - In dye-sensitized solar cells (DSCs), the electron transfer from photoexcited dye molecules to semiconductor substrates remains a major bottleneck. Replacing TiO2 with ZnO is expected to enhance the efficiency of DSCs, owing to the latter possesses a much larger electron mobility, but similar bandgap and band positions as TiO2 remain. However, the record efficiency of ZnO-based DSCs is only 7% compared with 13% of TiO2-based DSCs due to the even slower electron-transfer rate in ZnO-based DSCs, which becomes a long-standing puzzle. Here, we computationally investigate the electron transfer from the dye molecule into ZnO and TiO2, respectively, by performing the first-principles calculations within the frame of the Marcus theory. The predicted electron-transfer rate in the TiO2 based DSC is about 1.15 * 10(9) s(-1), a factor of 15 faster than that of the ZnO based DSC, which is in good agreement with experimental data. We find that the much larger density of states of the TiO2 compared with ZnO near the conduction band edge is the dominant factor, which is responsible for the faster electron transfer rate in TiO2-based DSCs. These denser states provide additional efficient channels for the electron transfer. We also provide design principles to boost the efficiency of DSCs through surface engineering of high mobility photoanode semiconductors. PMID- 27282780 TI - Organizing pneumonia in mice and men. AB - BACKGROUND: Organizing pneumonia is a reaction pattern and an inflammatory response to acute lung injuries, and is characterized by intraluminal plugs of granulation tissue in distal airspaces. In contrast to other fibrotic pulmonary diseases, organizing pneumonia is generally responsive to corticosteroids. However, some patients do not respond to treatment, leading to respiratory failure and potentially death (up to 15 % of patients). In order to devise new therapeutic strategies, a better understanding of the disease's pathomechanisms is warranted. We previously generated a mouse model overexpressing CCL2, which generates organizing pneumonia-like changes, morphologically comparable to human patients. In this study, we investigated whether the histopathological similarities of human and murine pulmonary organizing pneumonia lesions also involve similar molecular pathways. METHODS: We analyzed the similarities and differences of fibrosis-associated gene expression in individual compartments from patients with organizing pneumonia and transgenic (CCL2) mice using laser assisted microdissection, real-time PCR and immunohistochemistry. RESULTS: Gene expression profiling of human and murine organizing pneumonia lesions showed in part comparable expression levels of pivotal genes, notably of TGFB1/Tgfb1, TIMP1/Timp1, TIMP2/Timp2, COL3A1/Col3a1, CXCL12/Cxcl12, MMP2/Mmp2 and IL6/Il6. Hence, the transgenic CCL2 mouse model shows not only pathogenomic and morphological features of human organizing pneumonia but also a similar inflammatory profile. CONCLUSIONS: We suggest that the CCL2-overexpressing transgenic mouse model (CCL2 Tg mice) is suitable for further investigation of fibrotic pulmonary remodeling, particularly of organizing pneumonia pathogenesis and for the search for novel therapeutic strategies. PMID- 27282782 TI - Corrigendum: Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining. PMID- 27282783 TI - Monistic dualism and the body electric: An ontology of disease, patient and clinician for person-centred healthcare. AB - Ontology is involved in medical care, because what both doctors and patients think the disease, the patient and the doctor are affects the giving and receiving of care, and hence the definition of medical care as profession. Going back to ancient philosophical views of disease as 'bounded entity' or as 'relation' (still echoed in contemporary theories and mindsets), I propose a way to think ontologically about disease that places it in necessary connection with the patient as person. Drawing on Augustine's views on disease, bodily integrity, and the human person as mind-body unit, I speak of 'monistic dualism' as the view where the unit and health of the person is continuously and personally generated by the mind's attention to and action on the body, whether the body is impaired or not. Monistic dualism is identified as the ontological position of both patients who are (or can become) healthy within illness and clinicians who are 'healthy' in their profession. It is what guides both to create what their body is in a personal state of integrity or health. This 'metaphysical body' is termed 'the body electric' in patients, and I argue that clinicians can attend properly to the diseased body by attending to patients' metaphysical body. As clinicians offer metaphysical care to themselves, employing monistic dualism to create their metaphysical body, they should not deny it to patients. Ontology cannot be part of medical care without making metaphysical care a requirement. PMID- 27282784 TI - Toll-like receptors 2 and 4 exert opposite effects on the contractile response induced by serotonin in mouse colon: role of serotonin receptors. AB - What is the central question of this study? The action of Toll-like receptors (TLRs) 2 and 4 on the motor response to serotonin in mouse colon has not previously been reported. What is the main finding and its importance? Toll-like receptors 2 and 4 modulate the serotonin-induced contractile response in mouse colon by modifying the expression of serotonin (5-HT) receptors. Alterations in 5 HT2A and 5-HT2C receptors explain the increase of the response to serotonin in TLR2(-/-) mice. Alterations in 5-HT2C and 5-HT4 receptors explain the suppression of the response to serotonin in TLR4(-/-) mice. The microbiota, through Toll-like receptors (TLRs), may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in spontaneous contractions and in the serotonin (5-HT)-induced motor response in mouse colon, and assessed the 5-HT receptors involved. Muscle contractility studies to evaluate the intestinal spontaneous motility and the response to 5-HT were performed in the colon from wild-type (WT), TLR2(-/-) , TLR4(-/-) and TLR2/4 double knockout (DKO) mice. The 5-HT receptor mRNA expression was determined by real-time PCR. The amplitude and frequency of the spontaneous contractions of the colon were smaller in TLR4(-/-) and TLR2/4 DKO mice with respect to WT mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 100 MUm 5-HT evoked a contractile response. The contractile response induced by 5-HT was significantly higher in TLR2(-/-) than in WT mice. In TLR4(-/-) mice, 5-HT did not evoke any contractile response. The mRNA expression of 5-HT2A was increased in TLR2(-/-) and TLR2/4 DKO mice. The 5-HT2C and 5-HT4 mRNA expressions were increased in TLR4(-/-) and TLR2/4 DKO mice. The 5-HT2C mRNA expression was diminished in TLR2(-/-) mice. The 5-HT3 mRNA expression was increased in TLR2(-/-) , TLR4(-/-) and TLR2/4 DKO mice. The 5-HT7 mRNA expression was diminished in TLR2/4 DKO mice. In WT, TLR2(-/-) and TLR2/4 DKO mice, 5-HT2 , 5-HT3 , 5-HT4 and 5-HT7 receptor antagonists reduced or blocked the contractile response evoked by 5-HT. We postulate that TLR2 and TLR4 modulate the serotonin contractile motor response in mouse colon in an opposing manner by modifying the expression of several serotonin receptors. PMID- 27282785 TI - A novel RHCE*02 allele, containing the single-nucleotide change c.460A>G, encodes weakened expression of C and e antigens. AB - We report a novel RHCE*02 allele in a Swedish blood donor that is characterized by the change c.460A>G (Arg154Gly). The blood donor's red blood cells showed variable reactivity with different monoclonal anti-C and anti-e and antigen strength was markedly weakened. We believe that these changes represent both a quantitative and qualitative alteration of the antigens encoded by this allele. PMID- 27282786 TI - (Challenges of vaccination in older people. Can we circumvent immunosenescence?). PMID- 27282787 TI - The impact of menopause on work ability in women with severe menopausal symptoms. AB - OBJECTIVE: To measure the impact of menopause on work ability in women with severe menopausal symptoms. STUDY DESIGN: This cross-sectional study compared the work ability of a sample of otherwise healthy employed Dutch women (n=205) with that of a sample of first-time attendees of a menopause clinic (n=60); both groups were aged 44-60 years. Self-reported questionnaire data assessing work ability (Work Ability Index; WAI) and menopausal symptoms (Greene Climacteric Scale; GCS) were used. MAIN OUTCOME MEASURES: Logistic regression analyses were used to examine whether women with severe menopausal symptoms were more likely to have low work ability (defined as a score <37.0 points on the WAI) than were women in the reference group, after adjustment for individual and lifestyle factors. RESULTS: Symptomatic women had significantly higher total GCS scores (mean 26.7 vs 14.2, t=10.8, P<0.001) and significantly lower WAI scores (median 32.0 vs 40.0, U=2380, P<0.001) than the reference group. They were 8.4 times more likely to report low work ability than their healthy counterparts: 76.7% versus 30.2% (OR 8.4, 95% CI 4.1-17.2). CONCLUSIONS: Over three-quarters of symptomatic menopausal women report serious problems in dealing with the physical and mental demands of their work (recorded here as low work ability); hence these women might be at risk of prolonged sickness absence from work. PMID- 27282788 TI - What doctors need to know: Prescribing or not for the oldest old. AB - Given the global increase in the number of people over the age of 85, there is a growing body of work concerning this group, termed the oldest old. Much of this work is confined to the literature specialising in geriatrics and the more generic health care papers refer to 'older people' with little definition of what is meant by 'older'. Iatrogenesis (ill health caused by doctors) is a major issue and general practitioners (GPs) need practical help in prescribing for the oldest old. This paper presents a narrative review of the literature on prescribing and the oldest old. The results showed that all papers sourced referred to prescribing for the 'old' as those aged over 65, with only scant mention of oldest old. Yet prescribing for the oldest old involves clinical judgement and knowledge of the patient. It includes weighing up what will do good, cause no harm and is acceptable to the individual. GPs have to make treatment choices mostly in isolation from colleagues, during time-limited consultations and with few relevant guidelines on managing multi-morbidities in the oldest old. A major issue in prescribing for people over the age of 85 is that guidelines for diseases are based on trials with younger adults, outline the best practice for one disease in isolation (i.e. not in the presence of other diseases) and take little account of the interactions between the drugs used in managing several diseases in frail older people. There is a growing body of work, however, calling for specialist services for the oldest old. PMID- 27282789 TI - Hypertension and age at onset of natural menopause in Korean postmenopausal women: Results from the Korea National Health and Nutrition Examination Survey (2008-2013). AB - OBJECTIVES: Menopause is a natural phenomenon of aging, although the timing and management of menopause can significantly affect a woman's quality of life. It is therefore important to identify measures to ensure a healthy menopause. We set out to investigate the association between hypertension and early menopause in Korean women. STUDY DESIGN: This cross-sectional study was based on 2008-2013 data from the Korea National Health and Nutrition Examination Survey (KNHANES). Of the 53,829 participants surveyed, 13,584 women were selected. We analyzed the contents of the health interview, health examination, and nutrition survey. MAIN OUTCOME MEASURE: The main outcome was defined based on hazard ratios (HR) to identify the effects of hypertension on age at onset of menopause. RESULTS: Among postmenopausal women (n=6650), the mean age at onset of menopause was 50.4 years. Premenopausal hypertension was statistically significantly associated with age at menopause, oral contraceptive usage, household income, education level, occupation, marital status and smoking and drinking habits. With lower age at diagnosis of hypertension, HRs for menopause tended to be higher, and hypertension diagnosed before age 40 years conferred a statistically significantly higher HR (Model 1, HR=2.32, 95% CI=1.87-2.88; Model 2, HR=2.31, 95% CI=1.86-2.86; Model 3, HR=2.23, 95% CI=1.80-2.77; Model 4, HR=2.00, 95% CI=1.52-2.63). CONCLUSION: Premature menopause is strongly associated with lifestyle factors, in combination with incomplete management of chronic diseases. Our findings support the hypothesis that younger age at diagnosis of hypertension is associated with younger age at onset of menopause in Korean women. PMID- 27282790 TI - Coping with menopausal symptoms: An internet survey of Belgian postmenopausal women. AB - OBJECTIVES: An internet survey was performed to obtain data on the current use in Belgium of hormone replacement therapy and alternative treatments for the alleviation of menopausal symptoms. A supplementary aim was to assess the use of opt-in internet opinion panels (TalkToChange, http://www.talktochange.com, and GMI, http://www.gmi-mr.com/global-panel) as a potential new way to obtain data on menopausal issues. STUDY DESIGN: Data were collected via an internet platform from 696 postmenopausal women aged 45-60 years. OUTCOME MEASURES: Respondents were asked questions about their socio-demographic profile, their experience of the menopause, the burden of the menopause, its impact on their quality of life and the treatment of menopausal symptoms (if any). RESULTS: The opt-in internet opinion panels proved a quick way (19days) to obtain reliable information with a low error margin (3.7%). The online survey collected detailed socio-demographic data. Almost all of the women (98%) had heard about the menopause before. Sixty one percent perceived the menopause as a temporary phase (17% thought it lasted for one or two years and 44% thought it lasted for three to five years) and only 39% realized the menopause would last for the rest of their life. Twenty-three percent of the women reported any kind of impact of the menopause on their quality of life. However, for the other 77% the menopause had resulted in complaints. No differences according to the women's age, level of education or professional status were found in this respect. Sixty-nine percent of the women had 'ever' used some type of treatment for menopausal symptoms and 53% were currently using a treatment. Forty percent of those with more than three symptoms were currently untreated. Of those who were not on hormone replacement therapy (HRT), 61% would not consider taking it (54% were 'strongly opposed' and 7% simply 'opposed'), while 8% would consider asking their doctor for HRT. Among those women who were opposed to HRT, 25% indicated that they were afraid of the increased risk of breast cancer, 34% cited cardiovascular risks and 26% were worried about weight gain. In this Belgian sample, HRT was used significantly more often by French-speaking women (32%) than by Dutch-speaking women (9%) (OR 4.4, p<0.0001). The alternatives to HRT had a high satisfaction rate among users. Relaxation techniques, regular physical activity, acupuncture and avoiding stress had satisfaction rates similar to that with HRT. It was not possible to compare the alternatives in the same women. Nor was it possible to assess whether more pronounced symptoms required a specific treatment. CONCLUSION: Opt-in internet opinion panels proved a quick and efficient way to gather data on menopausal issues in Belgium. Despite the high levels of awareness and knowledge, there is some confusion concerning the duration of the menopause, and its common perception as a temporary condition is likely to mean that the menopausal burden is substantially underestimated. Many symptomatic women are untreated. PMID- 27282791 TI - Predictors of functional disability in mild cognitive impairment and dementia. AB - OBJECTIVE: Knowledge about factors predicting functional disability in mild cognitive impairment (MCI) and dementia would help health care providers to identify those patients who are at high risk of functional disability. Previous research is scarce and focused on only a small number of possible predictors. The aim of this study was to identify predictors of functional disability in patients with MCI and dementia. STUDY DESIGN: Cross-sectional cohort study. MAIN OUTCOME MEASURES: Data from patients who visited a memory clinic between 2011 and 2015 were evaluated. The Disability Assessment for Dementia (DAD) was used to assess functional disability. Patients diagnosed with MCI or dementia and with a DAD score available were included. This led to the inclusion of 474 patients. Univariate analyses with a broad range of variables were performed to detect factors that had a significant relationship to the DAD score. Age, gender and variables with a p-value of 0.1 or lower in the univariate analyses were taken into a multivariable analysis. This multiple linear regression analysis was performed to determine which variables were independently associated with the DAD score. MAIN RESULTS: Our multivariable model explained 42% of the variance in the DAD score. Independent predictors of the DAD score were age (B=0.03, 95%CI=0.002 0.05), gender (B=-0.43, 95%CI=-0.78 to -0.07), score on the Clinical Dementia Rating scale (CDR) (B=1.53, 95%CI=1.07-1.99 for CDR 1, B=2.93, 95%CI=2.28-3.58 for CDR 2, B=3.96, 95%CI=2.65-5.27 for CDR 3) and level of physical activity (B=0.56, 95%CI=0.05-1.07). CONCLUSION: Older age, male gender, higher CDR score and lower levels of physical activity are independent predictors of functional disability in MCI and dementia. PMID- 27282792 TI - Association between hematologic parameters and functional impairment among geriatric inpatients: Data of a prospective cross-sectional multicenter study ("GeriPravalenz2013"). AB - OBJECTIVES: Objective of this study was to analyse the association between impairment of Barthel Index items and hematologic parameters in geriatric inpatients. METHODS: Patient recruitment of the "GeriPravalenz2013" study has been described before. INCLUSION CRITERIA: in-patient aged>=70years; exclusion criteria: actual cancer disease or cancer associated treatment. Anemia was defined according to WHO criteria. Physical impairment was assessed by Barthel Index (BI). Association between all 10 items of the BI and hematologic parameters was statistically evaluated. RESULTS: Anemia prevalence was 55.1% (319/579) with BI impairment in 96.2% patients. T-test revealed significant lower BI in anemic patients (47.9 vs 54.3; p=0.004). Binary logistic regression revealed that growing age, reduced MCV, reduced iron levels and reduced Hb levels were associated with increased impairment of several items of the Barthel-Index. Interestingly, increased levels of albumin and folic acid (FA) were associated with increased impairment of BI items. CONCLUSION: Anemia and lower levels of anemia related parameters showed a negative impact on ADL and physical performance based on BI items. An impaired total BI should result in an analysis of BI subitems, particularly if anemia related laboratory parameters are deviant. Reasons for the negative impact of elevated FA and albumin levels on BI remain speculative. PMID- 27282793 TI - Inhaled medication usage in post-menopausal women and lifetime tobacco smoke exposure: The Women's Health Initiative Observational Study. AB - OBJECTIVE: While active smoking is a causal agent in respiratory disease, the independent role of secondhand smoke (SHS) merits further investigation. We investigated associations between lifetime active smoking and exposure to secondhand smoke - studied independently - and current use of 1 or more inhaled medications as a surrogate for prevalent pulmonary disease in post-menopausal women. STUDY DESIGN: Information on lifetime active and passive tobacco exposure and inhaled pulmonary medication usage at enrollment was collected from 88,185 postmenopausal women aged 50-79 enrolled in the Women's Health Initiative Observational Study from 1993 to 1998 at 40 centers in the United States. Participants were recruited from localities surrounding the study centers using a variety of methods, including informational mailings and mass media campaigns. MAIN OUTCOME MEASURES: Multivariate adjusted regression models were used to estimate odds ratios and 95% CI according to levels of active smoking and SHS exposure, and trends were tested across categories. RESULTS: Ever active smokers had an overall OR of 1.97 (95% CI 1.58-2.45) for having one or more prescribed inhaled medication compared with never-smoking women not exposed to active or passive smoke. The overall OR for using inhalers for never-smoking women exposed to any SHS compared with the same reference group was 1.33 (95% CI 1.07-1.65). In a quantified analysis of SHS, never-smoking women with the highest levels of lifetime SHS exposure had an estimated risk of inhaled medication usage of 1.74 (95% CI 1.32-2.30). CONCLUSIONS: The risk of requiring one or more prescribed inhaled medications for pulmonary disease was significantly higher in post menopausal women who ever smoked or who had lifetime exposure to SHS. PMID- 27282794 TI - The genetics of exceptional longevity: Insights from centenarians. AB - As the world population ages, so the prevalence increases of individuals aged 100 years or more, known as centenarians. Reaching this age has been described as exceptional longevity (EL) and is attributed to both genetic and environmental factors. Many genetic variations known to affect life expectancy exist in centenarians. This review of studies conducted on centenarians and supercentenarians (older than 110 years) updates knowledge of the impacts on longevity of the twenty most widely investigated single nucleotide polymorphisms (SNPs). PMID- 27282795 TI - Identification of higher hospital costs and more frequent admissions among mid aged Australian women who self-report diabetes mellitus. AB - OBJECTIVE: To ascertain whether the hospital costs for mid-aged Australian women who self-reported diabetes mellitus (DM) and who had one or more hospital admission during an eight and a half year period were higher than the hospital costs for other similarly aged non-DM women. METHODS: The sample comprised 2,392 mid-aged women, resident in New South Wales (NSW) Australia and participating in the Australian Longitudinal Study on Women's Health (ALSWH), who had any NSW hospital admissions during the eight and a half year period 1 July 2000 to 31 December 2008. Analyses were conducted on linked data from ALSWH surveys and the NSW Admitted Patient Data Collection (APDC). Hospital costs were compared for the DM and non-DM cohorts of women. A generalized linear model measured the association between hospital costs and self-reported DM. RESULTS: Eight and a half year hospital costs were 41% higher for women who self-reported DM in the ALSWH surveys (p<0.0001). On average, women who self-reported DM had significantly (p<0.0001) more hospital admissions (5.3) than women with no reported DM (3.4). The average hospital stay per admission was not significantly different between the two groups of women. CONCLUSIONS: Self-reported DM status in mid-aged Australian women is a predictor of higher hospital costs. This simple measure can be a useful indicator for public policy makers planning early-stage interventions that target people in the population at risk of DM. PMID- 27282796 TI - Patterns and correlates of time use and energy expenditure in older Australian workers: A descriptive study. AB - BACKGROUND: How people use their time has health implications, but use of time may be influenced by factors such as age, sex, education and health. OBJECTIVE: This study aimed to provide detailed information on the daily activity patterns of older working people. STUDY DESIGN: 139 older Australian adults (aged 50-79 years) undertook comprehensive interviews on their use of time. This paper presents a cross-sectional analysis of the baseline findings from a longitudinal study. MAIN OUTCOME MEASURES: Use of time was measured using the Multimedia Activity Recall for Children and Adults (MARCA), administered via computer assisted phone interview. Activity patterns were described, and compared on the basis of sex, education and health status. RESULTS: The main activities undertaken were sleep (mean 466min/day), work (mean 233min/day) and chores (mean 160min/day), with little time spent on physical activity (mean 13min/day). Women spent more time doing chores (p<0.001) while men spent more time on vigorous activities (p<0.001). Participants with "fair" health spent less time on inside chores (p=0.05) and grooming (p=0.02) than healthier participants. CONCLUSIONS: Healthy lifestyle interventions for older workers should aim to increase physical activity levels by targeting specific activities, depending on sex and health status. PMID- 27282797 TI - Effect of non-surgical periodontal therapy on insulin resistance in patients with type II diabetes mellitus and chronic periodontitis, as assessed by C-peptide and the Homeostasis Assessment Index. AB - AIM: A bidirectional relationship exists between diabetes and periodontitis. In the present clinical trial, we evaluated the effects of non-surgical periodontal therapy (NSPT) on insulin resistance in patients with type II diabetes mellitus (DM) and chronic periodontitis. METHODS: Forty chronic periodontitis patients with type II DM were selected and equally allocated to case and control groups. All patients were assessed for periodontal parameters and systemic parameters. The case group received NSPT, and both groups were re-evaluated after 3 months. RESULTS: All periodontal parameters were found to be significantly improved in the case group compared to the control group 3 months after NSPT. The mean differences in systemic parameters, such as fasting serum C-peptide, Homeostasis Assessment (HOMA) Index-insulin resistance, and HOMA-insulin sensitivity, from baseline to 3 months for the case group were 0.544 +/- 0.73, 0.54 +/- 0.63, and 25.44 +/- 36.81, respectively; for the control group, they were significant at 1.66 +/- 1.89, -1.48 +/- 1.86, and 31.42 +/- 38.82 respectively (P < 0.05). There was a significant decrease in fasting blood glucose and glycosylated hemoglobin A1c from baseline to 3 months in the case group (P < 0.05). CONCLUSION: The present study showed that periodontal inflammation could affect glycemic control and insulin resistance. Effective periodontal therapy reduced insulin resistance and improved periodontal health status and insulin sensitivity in patients with type II DM and chronic periodontitis. PMID- 27282798 TI - Conception, realization and qualification of a radioactive clean room lab facility dedicated to the synthesis of radiolabeled API for human ADME studies. AB - The human absorption, distribution, metabolism and elimination study administering radiolabeled drugs to human volunteers is an important clinical study in the development program of new drug candidates. The manufacture of radiolabeled Active Pharmaceutical Ingredients is covered by national drug laws and may come within the scope of regulatory GMP requirements. Additionally, authorities may request an appropriate environmental zoning to minimize the risk of microbiological contaminations particularly during the synthesis of radiolabeled Active Pharmaceutical Ingredients intended for parenteral application. Thus, a radioactive clean room lab facility in line with both GMP and radiation safety regulations was installed and the environmental zoning validated by appropriate testing of technical parameters and microbial and particle monitoring. The considerations detailed in this paper cover only GMP aspects related to the synthesis of radioactive drug substance. The subsequent, final formulation step in the overall process for manufacturing of radioactive drug product for any kind of administration is not within the scope of this paper. Under these qualified and controlled environmental conditions, we are now in a position to provide radiolabeled drug substances for all kinds of drug administration including both po and iv. PMID- 27282799 TI - Evaluation of the VIDAS glutamate dehydrogenase assay for the detection of Clostridium difficile. AB - We evaluated the performance of the VIDAS GDH assay for the detection of Clostridium difficile. In total, 350 fecal specimens collected from patients clinically suspected of having CDI were analyzed by C. difficile culture and enzyme-linked fluorescent immunoassay (VIDAS GDH); the results were compared with those of toxigenic C. difficile culture (TC), PCR (Xpert C. difficile assay), and toxin AB EIA (VIDAS CDAB). The numbers of culture-positive and culture-negative samples were 108 and 242, respectively. The concordance between the GDH assay and C. difficile culture was 90.3%. With PCR, 12 more samples were found to be positive in GDH-positive/C. difficile culture-negative specimens. Thus, the concordance between GDH assay and C. difficile culture/PCR was 93.7%. The sensitivity, specificity, positive predictive value, and negative predictive value of the VIDAS GDH assay were 97.2%, 87.2%, 77.2%, and 98.6%, respectively, based on the C. difficile culture, and 97.5%, 91.7%, 86.0%, and 98.6%, respectively, based on C. difficile culture/PCR. Positivity rates of the GDH assay were partially associated with those of semi-quantitative C. difficile cultures, which were maximized in grade 3 (>100 colony-forming unit [CFU]) compared with grade 1 (<10 CFU). We evaluated the two-step or three-step algorithm using GDH assay as a first step. No toxin EIA-positive case was found among GDH-negative samples, and 60.8% (48/79) were TC- and/or PCR-positive among the GDH-positive/toxin EIA-negative samples. Thus, approximately 25% of the 350 samples required a confirmatory test (TC or PCR) in the GDH-toxin EIA algorithm, whereas only 2.3% of the total samples in GDH-PCR algorithm was discrepant and required another confirmatory test like TC. PMID- 27282800 TI - The anti-tumor effect of folate-targeted liposome microbubbles loaded with oridonin as ultrasound-triggered tumor-targeted therapeutic carrier system. AB - In this study, folate receptor (FR) targeted liposome microbubbles loaded with oridonin (ORI) (F-LMB-ORI), liposome loaded with ORI (L-ORI) and liposome microbubbles loaded with ORI (LMB-ORI) were prepared. In vitro release properties, cellular uptake and cytotoxicity in HepG-2 cells as well as in vivo antitumor effects in HepG-2 cells tumor-bearing mice of F-LMB-ORI, L-ORI and LMB ORI were evaluated upon ultrasound exposure. Results showed cytotoxicity assay on F-LMB-ORI gave IC50 of 0.508 +/- 0.018 umol/mL on HepG-2 cells and LMB-ORI; L-ORI gave IC50 of 2.424 +/- 0.116 umol/mL, 3.031 +/- 0.122 umol/mL in vitro, respectively. These drug delivery carriers were able to control the release of ORI. F-LMB-ORI exhibited higher binding to HepG-2 cells in comparison to LMB-ORI and L-ORI. F-LMB-ORI improved antitumor activity of ORI obviously in comparison to L-ORI, LMB-ORI under in vivo ultrasound. After the treatment for 14 d, the tumor inhibition ratio for F-LMB-ORI (the dose of ORI: 1.5 * 10-2 g.kg-1, once a day) was 87.6%, obviously higher than that of LMB-ORI group, L-ORI group and free ORI (the dose of ORI: 1.5 * 10-2 g.kg-1, once a day) which were 71.5%, 64.3% and 43.4%, respectively. PMID- 27282801 TI - New Members of the National Academy of Sciences: H. Dai, H. L. Ploegh, and M. S. Sanford / Chirality Medal: Andreas Pfaltz / Elected to the Akademie der Wissenschaften zu Gottingen and Award for International Cooperation of the Chinese Academy of Sciences: K. Kohse-Hoinghaus. PMID- 27282802 TI - A novel SMARCAL1 missense mutation that affects splicing in a severely affected Schimke immunoosseous dysplasia patient. AB - Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive disease characterized by skeletal dysplasia, focal segmental glomerulosclerosis, renal failure and immunodeficiency. In this work, we report the molecular studies undertaken in a severely affected SIOD patient that died at six years old due to nephropathy. The patient was screened for mutations using a targeted skeletal dysplasias panel. A homozygous novel missense mutation was identified, c.1615C > G (p.[Leu539Val]) that was predicted as mildly pathogenic by in silico pathogenicity prediction tools. However, splicing prediction software suggested that this variant may create a new splicing donor site in exon 9, which was subsequently confirmed using a minigene assay in HEK293 cells. Thus, the splicing alteration, c.1615C > G; r.1615c > g, 1615_1644del; (p.[Leu539_Ile548del]), results in the loss of 10 amino acids of the HARP-ATPase catalytic domain and the RPA-binding domain. Several studies have demonstrated a weak genotype-phenotype correlation among such patients. Thus, the molecular characterization has helped us to understand why a predicted weakly pathogenic missense mutation results in severe SIOD and should be considered in similar scenarios. PMID- 27282803 TI - Treatment with ulipristal acetate (Esmya((r))) and plasma levels of tacrolimus: a case report. PMID- 27282804 TI - Effects of acute exercise on monocyte subpopulations in metabolic syndrome patients. AB - OBJECTIVE: Acute exercise induces numerous changes in peripheral blood, e.g. counts of leukocytes. CD16pos monocytes, which play a role in the pathogenesis of arteriosclerosis and the metabolic syndrome (MetS), are among the blood cells with the highest fold increase through exercise. So far no studies have investigated the effect of exercise on the blood cell composition of patients with MetS. APPROACH AND RESULTS: Blood cell counts, a wide panel of laboratory tests, as well as lipid and protein content of monocytes and granulocytes were determined in healthy subjects, persons with metabolic risk and MetS patients before and after one minute of exercise at 400 W. Leukocyte counts increased significantly in all groups with CD14pos CD16pos monocytes showing the highest fold-change. In MetS patients the fold increase was smaller. They had a higher resting level of CD14pos CD16pos monocytes and a lower basal ratio of CD16neg /CD16pos monocytes. A similar ratio of these cells was induced in control and risk subjects after exercise. However, absolute counts of mobilized pro inflammatory monocytes did not differ significantly. Furthermore, we detected a decrease in protein content of monocytes in controls, but not in MetS patients. CONCLUSIONS: As strenuous exercise is able to mobilize the same amount of pro inflammatory monocytes in MetS patients as in healthy persons, the elevated basal level of these cells in MetS patients is likely to be caused by enhanced maturation rather than chronic mobilization. The removal of these monocytes from the endothelium might be part of the beneficial effect of exercise on vascular disease. (c) 2016 International Clinical Cytometry Society. PMID- 27282806 TI - A prototype reversible polymersome-stabilized H2S photoejector operating under pseudophysiological conditions. AB - Persistent self-assembled polymersome capsules are shown to solubilise and stabilize a new hydrosulfide-containing (), as well as hydroxylated (), malachite green derivatives in their leuco-forms in aqueous buffer solution. Photoirradiation resulted in reversible hydroxide release/hydrogen sulfide generation. Notably, the efficient augmentation of H2S concentration to physiologically-relevant levels is shown. PMID- 27282805 TI - Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord. AB - Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRalpha/beta and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down regulated pPDGFRalpha/beta levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway. PMID- 27282808 TI - Confidence in Assessment of Lumbar Spondylolysis Using Three-Dimensional Volumetric T2-Weighted MRI Compared With Limited Field of View, Decreased-Dose CT. AB - BACKGROUND: Limited z-axis-coverage computed tomography (CT) to evaluate for pediatric lumbar spondylolysis, altering the technique such that the dose to the patient is comparable or lower than radiographs, is currently used at our institution. The objective of the study was to determine whether volumetric 3 dimensional fast spin echo magnetic resonance imaging (3D MRI) can provide equal or greater diagnostic accuracy compared with limited CT in the diagnosis of pediatric lumbar spondylolysis without ionizing radiation. HYPOTHESIS: Volumetric 3D MRI can provide equal or greater diagnostic accuracy compared with low-dose CT for pediatric lumbar spondylolysis without ionizing radiation. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 2. METHODS: Three pediatric neuroradiologists evaluated 2-dimensional (2D) MRI, 2D + 3D MRI, and limited CT examinations in 42 pediatric patients who obtained imaging for low back pain and suspected spondylolysis. As there is no gold standard for the diagnosis of spondylolysis besides surgery, interobserver agreement and degree of confidence were compared to determine which modality is preferable. RESULTS: Decreased-dose CT provided a greater level of agreement than 2D MRI and 2D + 3D MRI. The kappa for rater agreement with 2D MRI, 2D + 3D MRI, and CT was 0.19, 0.32, and 1.0, respectively. All raters agreed in 31%, 40%, and 100% of cases with 2D MRI, 2D + 3D MRI, and CT. Lack of confidence was significantly lower with CT (0%) than with 2D MRI (30%) and 2D + 3D MRI (25%). CONCLUSION: For diagnosing spondylolysis, radiologist agreement and confidence trended toward improvement with the addition of a volumetric 3D MRI sequence to standard 2D MRI sequences compared with 2D MRI alone; however, agreement and confidence remain significantly greater using decreased-dose CT when compared with either MRI acquisition. CLINICAL RELEVANCE: Decreased-dose CT of the lumbar spine remains the optimal examination to confirm a high suspicion of spondylolysis, with dose essentially equivalent to radiographs. If clinical symptoms are not classic for spondylolysis, 2D MRI is still very good at detecting spondylolysis while remaining sensitive for detection of alternative diagnoses such as disc abnormalities and pars stress reaction. The data suggest that standard 2D MRI sequences should not be entirely replaced by a volumetric T2-weighted 3D sequence (despite promising features of rapid acquisition time, increased spatial resolution, and reconstruction capability). PMID- 27282807 TI - The complete genome of a baculovirus isolated from an insect of medical interest: Lonomia obliqua (Lepidoptera: Saturniidae). AB - Lonomia obliqua (Lepidoptera: Saturniidae) is a species of medical importance due to the severity of reactions caused by accidental contact with the caterpillar bristles. Several natural pathogens have been identified in L. obliqua, and among them the baculovirus Lonomia obliqua multiple nucleopolyhedrovirus (LoobMNPV). The complete genome of LoobMNPV was sequenced and shown to have 120,022 bp long with 134 putative open reading frames (ORFs). Phylogenetic analysis of the LoobMNPV genome showed that it belongs to Alphabaculovirus group I (lepidopteran infective NPV). A total of 12 unique ORFs were identified with no homologs in other sequenced baculovirus genomes. One of these, the predicted protein encoded by loob035, showed significant identity to an eukaryotic transcription terminator factor (TTF2) from the Lepidoptera Danaus plexippus, suggesting an independent acquisition through horizontal gene transfer. Homologs of cathepsin and chitinase genes, which are involved in host integument liquefaction and viral spread, were not found in this genome. As L. obliqua presents a gregarious behavior during the larvae stage the impact of this deletion might be neglectable. PMID- 27282809 TI - High Performance Liquid Chromatography at -196 degrees C. AB - Ultralow temperature high-performance liquid chromatography (HPLC) was developed using a liquefied gas as the mobile phase. HPLC separation of low molecular weight alkanes at -196 degrees C with liquid nitrogen mobile phase was successfully achieved, whereas their GC separation at -196 degrees C using helium gas mobile phase failed to elute the analytes due to strong adsorption. Prior to the further study of HPLC at -196 degrees C, the effect of column temperature on the chromatographic behavior was investigated, and it was found that the retention of analytes drastically increased when the column temperature was over the boiling point of the mobile phase. As the study of retention control in HPLC at -196 degrees C, the mobile phases of nitrogen and methane mixtures were investigated. The addition of methane to the nitrogen mobile phase suppressed the retention of the analytes (tetra-deuterated methane, ethane, and propane), that is, the retention on HPLC at ultralow temperature could be controlled by the mobile phase composition, akin to the typical retention in HPLC. The selectivity toward the n- and iso-alkane in HPLC at -196 degrees C was altered compared with that in GC separation at room temperature. A significant enhancement of retention of alkanes compared with alkanes were observed in HPLC at -196 degrees C. PMID- 27282810 TI - New paradigms in clonal evolution: punctuated equilibrium in cancer. AB - Evolutionary theories are themselves subject to evolution. Clonal evolution - the model that describes the initiation and progression of cancer - is entering a period of profound change, brought about largely by technological developments in genome analysis. A flurry of recent publications, using modern mathematical and bioinformatics techniques, have revealed both punctuated and neutral evolution phenomena that are poorly explained by the conventional graduated perspectives. In this review, we propose that a hybrid model, inspired by the evolutionary model of punctuated equilibrium, could better explain these recent observations. We also discuss the conceptual changes and clinical implications of variable evolutionary tempos. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 27282811 TI - Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices. AB - Therapeutic strategies have been reported that depend on synthetic network devices in which a urate-sensing transcriptional regulator detects pathological levels of urate and triggers production or release of urate oxidase. The transcription factor involved, HucR, is a member of the multiple antibiotic resistance (MarR) protein family. We show that protonation of stacked histidine residues at the pivot point of long helices that form the scaffold of the dimer interface leads to reversible formation of a molten globule state and significantly attenuated DNA binding at physiological temperatures. We also show that binding of urate to symmetrical sites in each protein lobe is communicated via the dimer interface. This is the first demonstration of regulation of a MarR family transcription factor by pH-dependent interconversion between a molten globule and a compact folded state. Our data further suggest that HucR may be utilized in synthetic devices that depend on detection of pH changes. PMID- 27282812 TI - Retroaortic Variant of Reverse Horseshoe Kidney With Butterfly Vertebrae Presenting as Neurogenic Bladder. AB - Horseshoe kidney is a relatively common congenital anomaly. In 95% of the cases, lower poles are connected to each other. In a small subset, an isthmus connects both upper poles (reverse horseshoe kidney). Almost always, the fusion of kidney poles occurs anterior to the aorta and vena cava. The fusion of renal poles posterior to both aorta and vena cava is extremely rare. Herein, we present a case with multiple rare congenital anomalies-retroaortic variant of reverse horseshoe kidney, retroaortic left renal vein, and butterfly vertebrae. PMID- 27282814 TI - Differential Diptera Succession Patterns on Decomposed Rabbit Carcasses in Three Different Habitats. AB - This study describes for the first time the necrophagous Diptera attracted to rabbit carcasses in three distinct habitats in Riyadh, Kingdom of Saudi Arabia (KSA). A mean number of 1,427 flies belonging to 8 families and 16 species were collected during the decomposition process of the rabbits at the three different sites. Carcasses in the agricultural habitat attracted 1,146 flies from 7 families and 14 species, compared to carcasses in the urban site, which attracted 249 flies from 5 families and 9 species. Carcasses in the desert site attracted the lowest number (28 flies from 4 families and 5 species). In the agricultural and desert sites, flies were represented at all decomposition stages. Also, in the urban site, flies were represented at all stages except the fresh and dry stages. Lucilia sericata Meigen was the most abundant species occurring in both the agricultural and desert sites, while Musca domestica L. was the most abundant species occurring in the urban site. The evidence presented here, therefore, suggests that L. sericata and M. domestica are potentially useful species for estimating minimal postmortem intervals in this region of KSA. PMID- 27282813 TI - Modeling the Geographic Distribution of Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the Contiguous United States. AB - In addition to serving as vectors of several other human pathogens, the black legged tick, Ixodes scapularis Say, and western black-legged tick, Ixodes pacificus Cooley and Kohls, are the primary vectors of the spirochete (Borrelia burgdorferi) that causes Lyme disease, the most common vector-borne disease in the United States. Over the past two decades, the geographic range of I. pacificus has changed modestly while, in contrast, the I. scapularis range has expanded substantially, which likely contributes to the concurrent expansion in the distribution of human Lyme disease cases in the Northeastern, North-Central and Mid-Atlantic states. Identifying counties that contain suitable habitat for these ticks that have not yet reported established vector populations can aid in targeting limited vector surveillance resources to areas where tick invasion and potential human risk are likely to occur. We used county-level vector distribution information and ensemble modeling to map the potential distribution of I. scapularis and I. pacificus in the contiguous United States as a function of climate, elevation, and forest cover. Results show that I. pacificus is currently present within much of the range classified by our model as suitable for establishment. In contrast, environmental conditions are suitable for I. scapularis to continue expanding its range into northwestern Minnesota, central and northern Michigan, within the Ohio River Valley, and inland from the southeastern and Gulf coasts. Overall, our ensemble models show suitable habitat for I. scapularis in 441 eastern counties and for I. pacificus in 11 western counties where surveillance records have not yet supported classification of the counties as established. PMID- 27282815 TI - Preliminary Report on the Reduction of Adult Mosquitoes in Housing Compounds in Western Kenya Using the ProVector Flower and Entobac Bait Pads Containing Bacillus thuringiensis israelensis With Honey Bait. AB - Reducing mosquito populations indoors and outdoors can have a significant impact on malaria and other mosquito-borne diseases. A new formulation and delivery system for Bacillus thuringiensis israelensis (Bti) was tested against adult mosquitoes. One Entobac bait with 7% Bti in a honey solution was placed within each ProVector Flower applicator. The applicators were placed in nine housing compounds, one on the outside of each home in Ahero and Nyalenda, Kenya, in June 2009. Seven housing compounds with no applicators were included as controls in the study area. After 1 mo, there was a significant reduction of mosquitoes in all nine compounds with the ProVector Flower compared to two of the seven control compounds. The overall mosquito population was reduced by 69% in housing compounds with the ProVector Flower whereas the mosquito population grew by nearly 15% in the control compounds. There was a significant reduction of the median number of mosquitoes in the test compounds than in the control compounds. The proportion of mosquitoes collected was significantly reduced in the test compounds within 1 mo for several species of Aedes, Anopheles, Coquillettidia, Culex, and Mansonia This study provides evidence that Bti-laced bait may be used as an alternative adulticide and be delivered in an applicator to reduce mosquito populations of several species. This method may significantly reduce the cost of pesticide application through target specificity and by reducing the amount of pesticide placed into the environment. PMID- 27282816 TI - Ecology of Bats, Their Ectoparasites, and Associated Pathogens on Saint Kitts Island. AB - Ectoparasites of bats and bat-associated pathogens are poorly studied in the Lesser Antilles Islands. We report on an 11-mo field study on Saint Kitts Island of bat populations, their associated ectoparasites, and pathogens. We report on five ectoparasite species, including four Streblidae (Diptera) and a Spinturnicidae (Acari). Several genotypes of unnamed Bartonella were isolated from bats and ectoparasites. Microfilaria of an undetermined Litomosoides spp. were detected in blood from Artibeus jamaicensis Leach (Chiroptera: Phyllostomidae) (and associated ectoparasites: Trichobius intermedius Peterson and Hurka (Diptera: Streblidae) and Periglischrus iheringi Oudemans (Acari: Spinturnicidae)). In addition, an Ehrlichia sp. and Rickettsia africae were detected in the blood of several bat species. Our study is one of the first surveys of ectoparasite-borne pathogens in wild mammals from St. Kitts. PMID- 27282817 TI - Reported Distribution of Aedes (Stegomyia) aegypti and Aedes (Stegomyia) albopictus in the United States, 1995-2016 (Diptera: Culicidae). AB - Aedes (Stegomyia) aegypti (L.) and Aedes (Stegomyia) albopictus (Skuse) transmit arboviruses that are increasing threats to human health in the Americas, particularly dengue, chikungunya, and Zika viruses. Epidemics of the associated arboviral diseases have been limited to South and Central America, Mexico, and the Caribbean in the Western Hemisphere, with only minor localized outbreaks in the United States. Nevertheless, accurate and up-to-date information for the geographical ranges of Ae. aegypti and Ae. albopictus in the United States is urgently needed to guide surveillance and enhance control capacity for these mosquitoes. We compiled county records for presence of Ae. aegypti and Ae. albopictus in the United States from 1995-2016, presented here in map format. Records were derived from the Centers for Disease Control and Prevention ArboNET database, VectorMap, the published literature, and a survey of mosquito control agencies, university researchers, and state and local health departments. Between January 1995 and March 2016, 183 counties from 26 states and the District of Columbia reported occurrence of Ae. aegypti, and 1,241 counties from 40 states and the District of Columbia reported occurrence of Ae. albopictus During the same time period, Ae. aegypti was collected in 3 or more years from 94 counties from 14 states and the District of Columbia, and Ae. albopictus was collected during 3 or more years from 514 counties in 34 states and the District of Columbia. Our findings underscore the need for systematic surveillance of Ae. aegypti and Ae. albopictus in the United States and delineate areas with risk for the transmission of these introduced arboviruses. PMID- 27282818 TI - mTOR signalling in the nucleus accumbens shell is critical for augmented effect of TFF3 on behavioural response to cocaine. AB - Neuropeptides play important roles in modulating the rewarding value of abused drugs. Trefoil factor 3 (TFF3) was recently reported to modulate withdrawal syndrome of morphine, but the effects of TFF3 on the cocaine-induced behavioral changes are still elusive. In the present study, cocaine-induced hyperlocomotion and conditioned place preference (CPP) rat paradigms were provided to investigate the role of TFF3 in the reward response to cocaine. High-performance liquid chromatography (HPLC) analysis was used to analyse the dopamine concentration. The results showed that systemic TFF3 administration (0.1 mg/kg i.p.) significantly augmented cocaine- induced hyperlocomotion and CPP formation, without any effects on locomotor activity and aversive or rewarding effects per se. TFF3 significantly augmented the increment of the dopamine concentration in the NAc and the activity of the mTOR signalling pathway induced by acute cocaine exposure (10 mg/kg, i.p.) in the NAc shell, but not the core. The Intra-NAc shell infusion of rapamycin blocked TFF3-induced hyperactivity in cocaine-treatment rats. These findings indicated that TFF3 could potentiate behavioural response to cocaine, which may be associated with regulating dopamine concentration. Furthermore, the findings indicated that mTOR signalling pathway in the NAc shell is important for TFF3-induced enhancement on the cocaine-induced behavioral changes. PMID- 27282820 TI - Hepatitis B virus is associated with the clinical features and survival rate of patients with intrahepatic cholangiocarcinoma. AB - BACKGROUND AND OBJECTIVE: The pathogenesis and development of intrahepatic cholangiocarcinoma (ICC) may be triggered by hepatitis B virus (HBV). We conducted this retrospective study to explore the potential association between HBV infection and the clinical features and survival rate of patients with ICC. METHODS: Patients with ICC who had undergone a curative resection were enrolled and divided into three groups according to the seropositivity of the hepatitis B surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). The groups were as follows: group I, HBsAg (+)/anti-HBc (+); group II, HBsAg (-)/anti-HBc (+); group III HBsAg (-)/anti-HBc (-). The symptoms, pathologic findings, and outcome information of all patients were retrospectively reviewed. The patient sera were isolated to detect anti-HCV, HBsAg, and anti-HBc. Surgical specimens were assessed by hematoxylin and eosin (HE) staining. The expression of cytokeratin 7 was evaluated by immunohistochemistry. Finally, the 1-, 3-, and 5 year cumulative survival rates were analyzed. RESULTS: Ninety-seven patients with ICC were enrolled in group I (n=26); group II, (n=50), and group III (n=21). A total of 26.8% (26/97) patients with ICC were positive for HBsAg. Patients with HBV-associated ICC tended to be younger (P=0.018), have lower CA19-9 levels (P=0.000), a higher alpha fetal protein (AFP) level (P=0.012) and prothrombin time (P=0.030), a higher risk of hepatic cirrhosis (P=0.001), and poor differentiation (P=0.028). The 1-, 3-, and 5-year cumulative survival rates for patients within the three groups were as follows: 27.3%, 0%, and 0% for group I, respectively; 62.5%, 30.0%, and 0% for group II, respectively; and 87.5%, 66.7%, and 50.0% for group III, respectively. The results were significantly different in an overall comparison (P=0.000). CONCLUSION: Patients with HBV-associated ICC showed different clinicopathological features and lower survival rates compared to patients with ICC without HBV infection. PMID- 27282819 TI - Addition of grape pomace extract to probiotic fermented goat milk: the effect on phenolic content, probiotic viability and sensory acceptability. AB - BACKGROUND: Grape pomace is a source of phenolic compounds, which are associated with health benefits in humans. Additionally, fermented dairy foods with probiotics can be good vehicles to deliver these bioactive compounds. The effects of the addition of grape pomace extract (GPE) on the total phenolic (TP) content, physico-chemical characteristics and viability of Lactobacillus acidophilus LA-5 or Lactobacillus rhamnosus HN001 in fermented goat milks prepared with grape juice were investigated. RESULTS: The TP concentration increased significantly in fermented milks with the addition of GPE. A protective effect of GPE on the viability of L. acidophilus was observed. However, after 14 days of storage, the populations of L. acidophilus were significantly lower when compared with those of L. rhamnosus, and only the last probiotic maintained its viability above 7 log CFU mL-1 throughout the period investigated. The sensory scores of flavor, color and overall acceptability of the fermented milk containing L. rhamnosus HN001 were significantly increased when GPE was added. CONCLUSION: The use of GPE might increase the functionality of probiotic fermented goat milk processed with L. rhamnosus HN001 and grape juice because grape polyphenols are known for their antioxidant properties and positive effect on the modulation of gut microbiota. (c) 2016 Society of Chemical Industry. PMID- 27282821 TI - 'Race' and HIV vulnerability in a transnational context: the case of Chinese immigrants to Canada. AB - Although immigrants' sustained connections with their homelands are well documented, so far we know little about how 'race' - in particular, conceptions of race back home - influences the HIV vulnerability of racialised immigrants to Western countries. Drawing on data from a multi-sited, qualitative study of Chinese immigrants to Canada, this paper presents a contextualised understanding of the impacts of race on HIV risk faced by these individuals in a transnational context. Data were collected from four study sites in Canada and China as part of a study investigating the relationship between HIV risk and transnationalism. Although race appears to have bearing on their risk perceptions and sexual practices, immigrants' understandings of race are not necessarily consistent with dominant discourses of race in Canada, but are also mediated by their racial habitus developed in China. Findings reveal the complex power dynamics - not just power asymmetries but also power fluidity - around race from a transnational perspective and thus challenge the assumed dichotomy of dominance and subordination underpinning traditional explanations of the relationship between race and HIV risk. In the context of transnationalism, researchers should go beyond a nation-bound concept of society (i.e. the host society) and take into account the simultaneous influence of both host and home countries on immigrant health. PMID- 27282822 TI - The BUME method: a new rapid and simple chloroform-free method for total lipid extraction of animal tissue. AB - In this study we present a simple and rapid method for tissue lipid extraction. Snap-frozen tissue (15-150 mg) is collected in 2 ml homogenization tubes. 500 MUl BUME mixture (butanol:methanol [3:1]) is added and automated homogenization of up to 24 frozen samples at a time in less than 60 seconds is performed, followed by a 5-minute single-phase extraction. After the addition of 500 MUl heptane:ethyl acetate (3:1) and 500 MUl 1% acetic acid a 5-minute two-phase extraction is performed. Lipids are recovered from the upper phase by automated liquid handling using a standard 96-tip robot. A second two-phase extraction is performed using 500 MUl heptane:ethyl acetate (3:1). Validation of the method showed that the extraction recoveries for the investigated lipids, which included sterols, glycerolipids, glycerophospholipids and sphingolipids were similar or better than for the Folch method. We also applied the method for lipid extraction of liver and heart and compared the lipid species profiles with profiles generated after Folch and MTBE extraction. We conclude that the BUME method is superior to the Folch method in terms of simplicity, through-put, automation, solvent consumption, economy, health and environment yet delivering lipid recoveries fully comparable to or better than the Folch method. PMID- 27282823 TI - Performance of MRS in metabolic profiling of the lumbar spinal cord in rat and mice. AB - OBJECT: In vivo magnetic resonance spectroscopy (MRS) of the rodent spinal cord (SC) is technically challenging. We investigated the feasibility of MRS in the SC of both rat and mice, by comparing the spectral characteristics. We assessed possible species dependent differences in the suitability for non-invasive metabolite monitoring in the SC. MATERIALS AND METHODS: MR spectra using a STEAM sequence were acquired from a rectangular voxel in lumbar SC of rats and mice, after a two-step shim procedure. RESULTS: In addition to total choline (tCho) and total creatine (tCr), seven and eleven metabolites were reliably detected in rats and mice, respectively. No significant differences were observed in metabolite concentrations or spectral characteristics between species. CONCLUSION: Identification and quantification of major metabolites including the neurotransmitters gamma-aminobutyric acid (GABA) and glycine (Gly) in the SC was successful in both rat and mice showing that investigation of SC neurochemical profiles is feasible in both species. PMID- 27282824 TI - Searching for certainty: findings predictive of appendicitis in equivocal ultrasound exams. AB - BACKGROUND: Ultrasound (US) is the preferred imaging modality for evaluating suspected pediatric appendicitis. However, borderline appendiceal enlargement or questionable inflammatory changes can confound interpretation and lead to equivocal exams. OBJECTIVE: The purpose of this study was to determine which findings on equivocal US exams are most predictive of appendicitis. MATERIALS AND METHODS: All US exams performed for suspected pediatric appendicitis from July 1, 2013, through July 9, 2014, were initially interpreted using a risk-stratified scoring system. Two blinded pediatric radiologists independently reviewed US exams designated as equivocal and recorded the following findings: increased wall thickness, loss of mural stratification, peri-appendiceal fat inflammation, peri appendiceal fluid, appendicolith and maximum appendiceal diameter. A third pediatric radiologist resolved discrepancies. US features were correlated with the final diagnosis via multivariate analysis. RESULTS: During the study period, 162/3,750 (4.3%) children had US exams initially interpreted as equivocal (mean age 9.8 +/- 3.8 years). Five outpatients were lost to follow-up. Forty-eight of the remaining 157 (30.6%) children had an operative diagnosis of appendicitis. Findings significantly associated with appendicitis were loss of mural stratification (odds ratio [OR] = 6.7, P=0.035), peri-appendiceal fat inflammation (OR = 10.0, P<0.0001) and appendicolith (OR = 15.8, P=0.025). While appendiceal diameter tended to be larger in patients with appendicitis, the difference was not statistically significant. CONCLUSION: Loss of mural stratification, peri-appendiceal fat inflammation and an appendicolith are significant predictors of appendicitis in children with otherwise equivocal US exams. While maximum appendiceal diameter is not statistically associated with appendicitis in our study, mean appendiceal diameter of 6.7 mm in those without appendicitis suggests that the customary upper normal limit of 6 mm is too sensitive. PMID- 27282825 TI - Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams. AB - BACKGROUND: Recent reports have suggested residual gadolinium deposition in the brain in subjects undergoing multiple contrast-enhanced MRI exams. These findings have raised some concerns regarding gadolinium-based contrast agent (GBCA) usage and retention in brain tissues. OBJECTIVE: To summarize findings of hyperintense brain structures on precontrast T1-weighted images in 21 children undergoing multiple GBCA MRI exams. MATERIALS AND METHODS: This retrospective study involved 21 patients, each of whom received multiple MRI examinations (range: 5-37 exams) with GBCA over the course of their medical treatment (duration from first to most recent exam: 1.2-12.9 years). The patients were between 0.9 and 14.4 years of age at the time of their first GBCA exam. Regions of interest were drawn in the dentate nucleus and the globus pallidus on 2-D fast spin echo images acquired at 1.5 T. The signal intensities of these two structures were normalized by that of the corpus callosum genu. Signal intensity ratios from these patients were compared to control patients of similar ages who have never received GBCA. RESULTS: Signal intensity ratios increased between the first and the most recent MRI exam in all 21 patients receiving GBCA, with an increase of 18.6%+/-12.7% (range: 0.5% to 47.5%) for the dentate nucleus and 12.4%+/-7.4% (range: -1.2% to 33.7%) for the globus pallidus (P<0.0001). Signal intensity ratios were also higher in GBCA patients than in controls (P<0.01). The degree of signal intensity enhancement did not correlate with statistical significance to the cumulative number or volume of GBCA administrations each patient received, the patient's age or the elapsed time between the first and most recent GBCA MRI exams. CONCLUSION: These results in children are consistent with recent findings in adults, suggesting possible gadolinium deposition in the brain. PMID- 27282826 TI - Queensland tick typhus in rural New South Wales. AB - We report five cases of Rickettsia australis infection from southern coastal New South Wales, Australia. All patients presented with a cutaneous eruption of erythematous papules and pustules and systemic features of malaise, headache, lymphadenopathy and myalgia. Acute kidney injury (AKI) was present in two of five cases and one of five cases had acute delirium. Improvement was only seen after treatment with doxycycline 100 mg b.i.d. Positive serology for R. australis was present in four of five cases and a positive polymerase chain reaction (PCR) was seen in one of five cases. Histology showed varying features, from neutrophilic vasculitis to Sweet's syndrome and lymphocytic vasculitis. Recent significant advances in the diagnosis of R. australis infection include an eschar swab or biopsy PCR and isolation of specific Rickettsia on serology. These investigations should be considered in the presence of any of the following features: eschar at site of a tick bite or lymphadenopathy and fever with an eruption of erythematous papules and pustules. PMID- 27282828 TI - Manganese doped-iron oxide nanoparticle clusters and their potential as agents for magnetic resonance imaging and hyperthermia. AB - A simple, one pot method to synthesize water-dispersible Mn doped iron oxide colloidal clusters constructed of nanoparticles arranged into secondary flower like structures was developed. This method allows the successful incorporation and homogeneous distribution of Mn within the nanoparticle iron oxide clusters. The formed clusters retain the desired morphological and structural features observed for pure iron oxide clusters, but possess intrinsic magnetic properties that arise from Mn doping. They show distinct performance as imaging contrast agents and excellent characteristics as heating mediators in magnetic fluid hyperthermia. It is expected that the outcomes of this study will open up new avenues for the exploitation of doped magnetic nanoparticle assemblies in biomedicine. PMID- 27282827 TI - Virus-induced gene silencing of the RPC5-like subunit of RNA polymerase III caused pleiotropic effects in Nicotiana benthamiana. AB - In eukaryotic cells, RNA polymerase III is highly conserved and transcribes housekeeping genes such as ribosomal 5S rRNA, tRNA and other small RNAs. The RPC5 like subunit is one of the 17 subunits forming RNAPIII and its exact functional roles in the transcription are poorly understood. In this work, we report that virus-induced gene silencing of transcripts encoding a putative RPC5-like subunit of the RNA Polymerase III in a model species Nicotiana benthamiana had pleiotropic effects, including but not limited to severe dwarfing appearance, chlorosis, nearly complete reduction of internodes and abnormal leaf shape. Using transcriptomic analysis, we identified genes and pathways affected by RPC5 silencing and thus presumably related to the cellular roles of the subunit as well as to the downstream cascade of reactions in response to partial loss of RNA Polymerase III function. Our results suggest that silencing of the RPC5L in N. benthamiana disrupted not only functions commonly associated with the core RNA Polymerase III transcripts, but also more diverse cellular processes, including responses to stress. We believe this is the first demonstration that activity of the RPC5 subunit is critical for proper functionality of RNA Polymerase III and normal plant development. PMID- 27282829 TI - A Report of Two Patients with Darier Disease and Hidradenitis Suppurativa. AB - We report two unique cases of patients with Darier disease and hidradenitis suppurativa. Although it is unknown whether there is a connection between the two diseases, it is possible that an interaction between sarcoendoplasmic reticulum calcium transport ATPase and Notch homolog 1, translocation-associated (Drosophila) caused both diseases in these individuals. PMID- 27282830 TI - Foot care behaviors among adults with type 2 diabetes. AB - AIM: The aim of the study was to determine factors influencing foot care behaviors among adults with type 2 diabetes. METHODS: A correlational descriptive study was conducted with a random sample of 160 adults with type 2 diabetes from the public hospital between April and July 2014. RESULTS: Just over 15% of the sample had a history of foot ulcers and almost 42% had numbness/tingling and pain in their feet. Positive foot care behaviors were correlated with higher income, higher educational attainment, lower body weight, positive attitude and higher awareness of diabetes and its management. CONCLUSION: Targeting type 2 diabetes people with low level of education, low income and overweight may help to enhance their foot care and reduce foot complications in similar populations, Implications. Those most at risk of foot problems should be targeted for education to increase their awareness of ways to prevent and to manage foot problems. PMID- 27282831 TI - Protective or destructive: High wall shear stress and atherosclerosis. PMID- 27282832 TI - Is the presence of AA amyloidosis associated with impaired coronary flow reserve? AB - BACKGROUND AND AIMS: Systemic amyloid A protein (AA) amyloidosis may occur as a complication of many chronic inflammatory disorders. Patients receiving inadequate anti-inflammatory and immunosuppressive therapies have an increased risk of developing systemic AA amyloidosis. Inflammation plays a role in all stages and the thrombotic complications of atherosclerosis. In the absence of epicardial coronary stenosis, coronary flow reserve (CFR) reflects coronary microvascular dysfunction. In the present study, we hypothesized that amyloid advanced subclinical inflammation in chronic inflammatory diseases (CID) patients may further affect coronary microcirculation. METHODS: Thirty-two patients with biopsy-diagnosed renal AA, 73 patients with non-amyloid CID, and a group of healthy volunteers were included in the study. The measurements of coronary flow velocity were performed by a single investigator with expertise in transthoracic Doppler harmonic echocardiography (TTDE). RESULTS: The AA amyloidosis subgroup had significantly lower CFR values than other non-amyloid CID patients and the control individuals (1.8 (1.5-2.1) vs. 2.1 (2.0-2.4) and 3.0 (2.8-3.2), p < 0.001). Multivariate logistic regression analysis indicated that the presence of AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR (p < 0.05). CONCLUSIONS: The presence of AA amyloidosis is related to decreased CFR values and the presence of AA amyloidosis and elevated hs - CRP independently predict impairment of the CFR. Therefore, patients with AA amyloidosis may have an increased risk of developing coronary artery diseases. PMID- 27282833 TI - PDNAsite: Identification of DNA-binding Site from Protein Sequence by Incorporating Spatial and Sequence Context. AB - Protein-DNA interactions are involved in many fundamental biological processes essential for cellular function. Most of the existing computational approaches employed only the sequence context of the target residue for its prediction. In the present study, for each target residue, we applied both the spatial context and the sequence context to construct the feature space. Subsequently, Latent Semantic Analysis (LSA) was applied to remove the redundancies in the feature space. Finally, a predictor (PDNAsite) was developed through the integration of the support vector machines (SVM) classifier and ensemble learning. Results on the PDNA-62 and the PDNA-224 datasets demonstrate that features extracted from spatial context provide more information than those from sequence context and the combination of them gives more performance gain. An analysis of the number of binding sites in the spatial context of the target site indicates that the interactions between binding sites next to each other are important for protein DNA recognition and their binding ability. The comparison between our proposed PDNAsite method and the existing methods indicate that PDNAsite outperforms most of the existing methods and is a useful tool for DNA-binding site identification. A web-server of our predictor (http://hlt.hitsz.edu.cn:8080/PDNAsite/) is made available for free public accessible to the biological research community. PMID- 27282834 TI - Role of Health Insurance Status in Interfacility Transfers of Patients With ST Elevation Myocardial Infarction. AB - Lack of health insurance is associated with interfacility transfer from emergency departments for several nonemergent conditions, but its association with transfers for ST-elevation myocardial infarction (STEMI), which requires timely definitive care for optimal outcomes, is unknown. Our objective was to determine whether insurance status is a predictor of interfacility transfer for emergency department visits with STEMI. We analyzed data from the 2006 to 2011 Nationwide Emergency Department Sample examining all emergency department visits for patients age 18 years and older with a diagnosis of STEMI and a disposition of interfacility transfer or hospitalization at the same institution. For emergency department visits with STEMI, our multivariate logistic regression model included emergency department disposition status (interfacility transfer vs hospitalization at the same institution) as the primary outcome, and insurance status (none vs any [including Medicare, Medicaid, and private insurance]) as the primary exposure. We found that among 1,377,827 emergency department STEMI visits, including 249,294 (18.1%) transfers, patients without health insurance (adjusted odds ratio 1.6, 95% CI 1.5 to 1.7) were more likely to be transferred than those with insurance. Lack of health insurance status was also an independent risk factor for transfer compared with each subcategory of health insurance, including Medicare, Medicaid, and private insurance. In conclusion, among patients presenting to United States emergency departments with STEMI, lack of insurance was an independent predictor of interfacility transfer. In conclusion, because interfacility transfer is associated with longer delays to definitive STEMI therapy than treatment at the same facility, lack of health insurance may lead to important health disparities among patients with STEMI. PMID- 27282835 TI - Cardiac Troponin T and I Release After a 30-km Run. AB - Prolonged endurance-type exercise is associated with elevated cardiac troponin (cTn) levels in asymptomatic recreational athletes. It is unclear whether exercise-induced cTn release mirrors a physiological or pathological underlying process. The aim of this study was to provide a direct comparison of the release kinetics of high-sensitivity cTnI (hs-cTnI) and T (hs-cTnT) after endurance-type exercise. In addition, the effect of remote ischemic preconditioning (RIPC), a cardioprotective strategy that limits ischemia-reperfusion injury, was investigated in a randomized controlled crossover manner. Twenty-five healthy volunteers completed an outdoor 30-km running trial preceded by RIPC (4 * 5 min 220 mm Hg unilateral occlusion) or control intervention. hs-cTnT, hs-cTnI, and sensitive cTnI (s-cTnI) concentrations were examined before, immediately after, 2 and 5 hours after the trial. The completion of a 30-km run resulted in a significant increase in circulating cTn (time: all p <0.001), with maximum hs cTnT, hs-cTnI, and s-cTnI levels of 47 +/- 27, 69 +/- 62, and 82 +/- 64 ng/L (mean +/- SD), respectively. Maximum hs-cTnT concentrations were measured in 60% of the participants at 2 hours after exercise, compared with maximum hs-cTnI and s-cTnI concentrations at 5 hours in 84% and 80% of the participants. Application of an RIPC stimulus did not reduce exercise-induced cTn release (time * trial: all p >0.5). In conclusion, in contrast to acute myocardial infarction, maximum hs-cTnT levels after exercise precede maximum hs-cTnI levels. Distinct release kinetics of hs-cTnT and hs-cTnI and the absence of an effect of RIPC favors the concept that exercise-induced cTn release may be mechanistically distinct from cTn release in acute myocardial infarction. PMID- 27282837 TI - Lesion guided radiofrequency thermocoagulation (L-RFTC) for hypothalamic hamartomas, nodular heterotopias and cortical dysplasias: Review and perspective. AB - Lesion guided radiofrequency thermocoagulation (L-RFTC) via stereotactically inserted coagulation probes is a further development of stereotactic thermocoagulation thalamotomy and stereo-EEG guided RFTC. In this method epileptogenic lesions detected via magnetic resonance imaging (MRI) move to the center of coagulation planning. Two surgical strategies can be applied: lesion disconnection and lesion destruction. This focused review collects all data published until January 2016 on L-RFTC for the indications hypothalamic hamartoma, periventricular nodular heterotopia and focal cortical dysplasia and describes technical issues, surgical objectives and outcomes. Special attention is given to the aspect of presurgical MRI requirements. PMID- 27282839 TI - The Alkaline Dissolution Rate of Calcite. AB - Due to the widespread presence of calcium carbonate on Earth, several geochemical systems, among which is the global CO2 cycle, are controlled to a large extent by the dissolution and precipitation of this mineral. For this reason, the dissolution of calcite has been thoroughly investigated for decades. Despite this intense activity, a consensual value of the dissolution rate of calcite has not been found yet. We show here that the inconsistency between the reported values stems mainly from the variability of the chemical and hydrodynamic conditions of measurement. The spreading of the values, when compared in identical conditions, is much less than expected and is interpreted in terms of sample surface topography. This analysis leads us to propose benchmark values of the alkaline dissolution rate of calcite compatible with all the published values, and a method to use them in various chemical and hydrodynamic contexts. PMID- 27282836 TI - Impairment of the humoral and CD4(+) T cell responses in HTLV-1-infected individuals immunized with tetanus toxoid. AB - T cells from HTLV-1-infected individuals have a decreased ability to proliferate after stimulation with recall antigens. This abnormality may be due to the production of regulatory cytokine or a dysfunctional antigen presentation. The aims of this study were to evaluate the antibody production and cytokine expression by lymphocytes before and after immunization with tetanus toxoid (TT) and to evaluate the immune response of monocytes after stimulation with TT and frequency of dendritic cells (DC) subsets. HTLV-1 carriers (HC) and uninfected controls (UC) with negative serology for TT were immunized with TT, and the antibody titers were determined by ELISA as well as the cell activation markers expression by monocytes. The frequencies of DC subsets were determined by flow cytometry. Following immunization, the IgG anti-TT titers and the frequency of CD4(+) T cells expressing IFN-gamma, TNF-alpha and IL-10 in response to TT were lower in the HC than in the UC. Additionally, monocytes from HC did not exhibit increased HLA-DR expression after stimulation with TT, and presented low numbers of DC subsets, therefore, it's necessary to perform functional studies with antigen-presenting cells. Collectively, our finding suggests that HC present an impairment of the humoral and CD4(+) T cell immune responses after vaccination. PMID- 27282838 TI - Lack of correlation between extracranial venous abnormalities and multiple sclerosis: a quantitative MRI study. AB - OBJECTIVE: We aimed to evaluate the presence of venous stenosis and blood flow abnormalities in the neck vessels of patients with multiple sclerosis (MS), in respect to a group of age- and sex-matched healthy controls (HC), and their possible relations with clinical variables using a semi-automated quantitative MRI method. METHODS: 45 patients with relapsing remitting MS and 40 HC were enrolled in this study. Flow rates and cross-sectional areas of arterial and venous neck vessels were assessed by phase-contrast MRI at two different neck levels (C2-C3 and C6-C7), and differences between groups were evaluated with an unpaired t-test. Correlation between blood flow variables and clinical parameters was analyzed with Spearman's test. RESULTS: A significant internal jugular vein (IJV) stenosis was found in 23/45 (51.1%) patients with MS and 18/40 (45.0%) HC. No differences were observed between patients with MS and HC for any of the flow measures obtained. No correlations were found between MRI measures and any of the tested clinical variables. CONCLUSION: No differences in the IJV area emerged at quantitative MRI evaluation, suggesting that stenosis of the extracranial veins is unrelated to MS. Furthermore, no flow differences in the neck vessels were found between patients with MS and HC in any of the tested flow measures, with no correlation with clinical variables. Our results confirm that the hypothesis of the presence of extracranial venous abnormalities in MS, both in terms of stenosis or flow measures, is not suitable. ADVANCES IN KNOWLEDGE: Neck venous drainage abnormalities have been claimed to be associated with MS. Conversely, our quantitative MRI analysis seems to exclude that extracranial venous alterations are related to the disease. PMID- 27282840 TI - Use of botulinum toxin for chronic pelvic pain. PMID- 27282841 TI - Distal myopathy with coexisting heterozygous TIA1 and MYH7 Variants. AB - TIA1 mutations cause Welander distal myopathy. MYH7 mutations result in various clinical phenotypes, including Laing distal myopathy and cardiomyopathy. We describe a family with coexisting TIA1 and MYH7 variants. The proband is a 67 year-old woman with easy tripping since childhood and progressive asymmetric distal limb weakness, but no cardiac involvement. Muscle biopsy showed rare rimmed vacuoles, minicore-like structures and congophilic inclusions. Her 66-year old sister has a mild distal myopathy, supraventricular tachycardia and hypertrophic cardiomyopathy. Both sisters carry the only known pathogenic TIA1 mutation and a heterozygous MYH7 variant (c.5459G > A; p.Arg1820Gln). Another sibling with isolated distal myopathy carries only the TIA1 mutation. MYH7 p.Arg1820Gln involves a highly conserved residue and is predicted to be deleterious. Furthermore, the proband's childhood-onset distal leg weakness and sister's cardiomyopathy suggest that MYH7 p.Arg1820Gln likely affects function, favoring a digenic etiology of the myopathy. PMID- 27282842 TI - Hypomelanosis of Ito (pigmentary mosaicism of the hypopigmented type) with endoplasmic reticulum stress in melanocytes. PMID- 27282843 TI - Outcomes of long-term iron supplementation in pediatric restless legs syndrome/periodic limb movement disorder (RLS/PLMD). AB - OBJECTIVES: Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) are thought to center around a genetically mediated sensitivity to iron insufficiency. Previous studies have shown the effectiveness of short-term iron therapy in children with low iron storage. Little is known, however, about long term iron treatment in children with RLS and PLMD. Therefore, we performed this study to assess the long-term effect of iron therapy in children with RLS and PLMD. METHODS: A retrospective chart review was performed for children who met the following criteria: A) diagnosed as having either RLS or PLMD, B) started on iron supplementation, C) followed up for >2 years in a sleep clinic. Baseline values for iron, ferritin, and periodic limb movement of sleep index (PLMS index) were defined in the three months leading up to the initiation of iron therapy. Values were also computed for follow-up periods of 3-6 months, 1-2 years, and >2 years. Serum iron and ferritin levels and PLMS index were compared between baseline and all subsequent follow-ups. RESULTS: In total, 105 patients met inclusion criteria, of whom 64 were diagnosed with PLMD alone, seven with RLS alone, and 35 with both RLS and PLMD. The average age was 10.2 +/- 5.3 years. Compared to the baseline (27.4 +/- 12.1 ng/ml), the average ferritin values at 3 6 months (45.62 +/- 21.2 ng/ml, p < 0.001, n = 34), 1-2 years (52.0 +/- 48.3 ng/ml, p <0.001, n = 63), and >2 years (54.7 +/- 40.5 ng/ml, p <0.001, n = 67) were all significantly increased. Inversely, compared to baseline (21 +/- 27.0/h, n = 66), PLMS index values at 3-6 months (7.5 +/- 9.5/h p < 0.05, n = 11), 1-2 years (6.9 +/- 8.9/h, p <0.001, n = 29), and >2 years (10 +/- 14.5/h, p <0.001, n = 31) were all significantly decreased. No significant change in serum iron levels was noted at any time point. CONCLUSION: While retrospective in nature, this study demonstrates a sustained improvement in PLMS index and maintenance of adequate ferritin levels >2 years after iron therapy initiation in our RLS/PLMD cohort with a long-term follow-up. Iron therapy appears to lead to long-lasting improvements in children with RLS/PLMD. PMID- 27282844 TI - Vinorelbine With Capecitabine, an Evergreen Doublet for Advanced Breast Cancer: A Systematic Literature Review and Pooled-Analysis of Phase II-III Studies. AB - Metastatic breast cancer (MBC) is treated with cytotoxic drugs or endocrine agents according to the site and extent of the disease, biology, previous treatments, and the patient's condition, comorbidities, and wishes. In MBC, vinorelbine (VRB) and capecitabine (X; VRB + X) are chemotherapy drugs that hold activity as first or later lines of therapy. We conducted a systematic literature review and meta-analysis to quantify the efficacy of the VRB + X combination in HER2-negative (HER2-) MBC. We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed VRB + X for patients with HER2- MBC. Pooled estimates of the overall response rate (RR), median progression-free survival (PFS), and overall survival (OS) were computed using random or fixed effects models. Twenty-seven studies were included in the analysis, encompassing a total of 1356 MBC patients. All were phase II (n = 21) or prospective/pilot (n = 5) trials, except for 1 that was a phase III controlled trial. The pooled estimate for the RR in first-line therapy (n = 16 trials) was 52.9% (95% confidence interval [CI], 46.5%-59.2%). For second-line trials, data were available in n = 9 studies and the overall RR was 41% (95% CI, 31.2%-51.6%). The pooled estimates for median PFS and OS in first-line therapy were 7.3 (95% CI, 6.2-8.3) and 22.3 (95% CI, 20-24.5) months, respectively. Vinorelbine + X, with the dose and schedules currently used in clinical practice, appears to be an effective and feasible chemotherapy for MBC, for first- and also for second-line therapy. PMID- 27282845 TI - Assessment of Residual Disease With Molecular Breast Imaging in Patients Undergoing Neoadjuvant Therapy: Association With Molecular Subtypes. AB - BACKGROUND: Assessment of residual disease after neoadjuvant therapy for breast cancer is an ongoing challenge of breast imaging. This study evaluates the accuracy of a novel dedicated system for molecular breast imaging (MBI) composed of the new generation of cadmium zinc telluride detectors in assessing residual disease after neoadjuvant therapy in patients with breast cancer. PATIENTS AND METHODS: Clinical data, imaging, surgical, and pathological findings of 51 women with breast cancer undergoing neoadjuvant therapy were recorded. MBI findings were correlated with surgical pathology results. Accuracy of MBI in predicting complete pathological response and size of residual disease was assessed according to molecular subtypes. RESULTS: The size of the largest focus of uptake on MBI correlated with the largest dimension measured on pathology (r = 0.55; P < .001). This correlation was stronger for triple negative and HER2/neu positive subtypes (r = 0.92 and 0.62, respectively). Sixteen patients (31%) had complete pathological response. The sensitivity and specificity of MBI for detecting residual disease were 83% (95% confidence interval [CI], 66-93) and 69% (95% CI, 42-88), respectively. For triple negative or HER2/neu positive disease the sensitivity and specificity were 88% (95% CI, 62-98) and 75% (95% CI, 43-93), respectively. CONCLUSION: The accuracy of MBI in assessing residual disease after neoadjuvant treatment might be related to the molecular subtype. Accuracy is highest in the triple negative and HER2/neu positive subtypes. PMID- 27282846 TI - From Evidence-based Medicine to Human-based Medicine in Psychosomatics. AB - Human-based medicine (HbM), a form of psychiatry that focuses not only on fragments and constructs but on the whole person, no longer finds its theoretical basis in the positivism of the modern era, but rather owes its central maxims to the post-modernist ideal that ultimate truths or objectivity in identifying the final cause of illness remain hidden from us for theoretical reasons alone. Evidence-based medicine (EbM) and HbM are thus not mutually exclusive opposites; rather, despite superficial differences in methods of diagnosis and treatment, EbM must be integrated into HbM as an indispensable component of the latter. Probably the most important difference between EbM and HbM lies in the aims and methods of treatment. In HbM the goal is no longer simply to make illnesses disappear but rather to allow the patient to return to a life that is as autonomous and happy as possible. The human being with all his or her potential and limitations once again becomes the measure of all things. This also implies, however, that the multidimensional diagnostics of HbM are oriented not only towards symptoms, pathogenesis, process and understanding but also to a greater degree towards the patient's resources. Treatment options and forms of therapy do not put the disease construct at the centre of the diagnostic and therapeutic interest, but have as their primary aim the reopening of the possibility of a largely autonomous and joyful life for the patient. PMID- 27282848 TI - Effect of Gender on Outcomes After Cardiac Resynchronization Therapy in Patients With a Narrow QRS Complex: A Subgroup Analysis of the EchoCRT Trial. AB - BACKGROUND: In EchoCRT, a randomized controlled trial evaluating the effect of cardiac resynchronization therapy (CRT) in patients with a QRS duration of <130 ms and echocardiographic evidence of left ventricular dyssynchrony, the primary outcome (death from any cause or first hospitalization for worsening heart failure) occurred more frequently in the CRT-ON when compared with the control group. In this prespecified subgroup analysis, we evaluated the effect of sex on clinical outcome in EchoCRT. METHODS AND RESULTS: In EchoCRT, 585 (72%) of included patients were men. At baseline, male patients had a higher incidence of ischemic cardiomyopathy and longer QRS duration. On uni- and multivariable analysis, no significant interaction was observed regarding sex for the primary or any of the secondary end points. Numerically, a higher all-cause mortality was observed in male patients randomized to CRT-ON versus CRT-OFF on univariable analysis (hazard ratio, 1.83; 95% confidence interval, 1.08-3.12); however, no statistically significant interaction compared with females randomized to CRT-ON versus CRT-OFF was noted (hazard ratio, 0.99; P interaction, 0.56). There was no difference in the primary safety end point of system-related complications, including CRT system- and implantation-related events. CONCLUSIONS: The largest hazard for all-cause mortality in EchoCRT was observed in men randomized to CRT ON; the comparison with women did not reach statistical significance, which may be because of the premature termination of the trial and the limited data. These results suggest that male sex may be a risk factor for harm by CRT in patients with narrow QRS width, an observation which deserves further investigation. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00683696. PMID- 27282847 TI - Appropriate Use and Clinical Impact of Echocardiographic "Evaluation of Murmur" in Pediatric Patients. AB - OBJECTIVE: To determine the appropriateness and yield of transthoracic echocardiograms (TTE) for murmur evaluation based on the pediatric Appropriate Use Criteria (AUC) and study the influence of patient age and physician experience on TTE appropriateness, yield, and ordering frequency. DESIGN: Retrospective review of medical records of patients referred to our practice for murmur evaluation from April to September 2014. Data collected included indication for TTE, patient age, physician experience since fellowship, TTE findings and exit diagnosis. Appropriateness was assigned based on the AUC document. SETTING: Pediatric cardiology clinics affiliated with a large pediatric cardiology practice. PATIENTS: One thousand seven hundred one consecutive patients (<= 18 years) referred to our practice for murmur evaluation. INTERVENTIONS: Not applicable OUTCOME MEASURES: The primary outcome was appropriateness of TTE orders. The secondary outcomes were the yield of abnormal TTE findings and the influence of patient age and physician experience on appropriateness, yield, and frequency of ordering TTEs. RESULTS: Of the 1701 patients referred for a murmur, 526 (30.9%) had a TTE [441/526 (83.8%) Appropriate; 85/526 (16.2%) Rarely Appropriate]. Abnormal findings were present in 130/441 rated Appropriate and none rated Rarely Appropriate. Infants <3 months had the highest rate of TTEs rated Appropriate and the highest yield of abnormal findings. Physicians with >20 years of experience not only had the lowest TTE ordering rate but also the lowest appropriateness rate with no difference in the yield of abnormal findings. CONCLUSIONS: Most TTEs ordered for murmur were for indications rated Appropriate. Abnormal findings were present in one-fourth and only those rated Appropriate. Patient age and physician experience can significantly influence TTE utilization. This information is helpful in designing quality initiatives to optimize TTE utilization for murmur evaluation. PMID- 27282849 TI - Two isocitrate dehydrogenases from a plant pathogen Xanthomonas campestris pv. campestris 8004. Bioinformatic analysis, enzymatic characterization, and implication in virulence. AB - Isocitrate dehydrogenase (IDH) is a key enzyme in the tricarboxylate (TCA) cycle, which may play an important role in the virulence of pathogenic bacteria. Here, two structurally different IDHs from a plant pathogen Xanthomonas campestris pv. campestris 8004 (XccIDH1 and XccIDH2) were characterized in detail. The recombinant XccIDH1 forms homodimer in solution, while the recombinant XccIDH2 is a typical monomer. Phylogenetic analysis showed that XccIDH1 belongs to the type I IDH subfamily and XccIDH2 groups into the monomeric IDH clade. Kinetic characterization demonstrated that XccIDH1's specificity towards NAD(+) was 110 fold greater than NADP(+) , while XccIDH2's specificity towards NADP(+) was 353 fold greater than NAD(+) . The putative coenzyme discriminating amino acids (Asp268, Ile269 and Ala275 for XccIDH1, and Lys589, His590 and Arg601 for XccIDH2) were studied by site-directed mutagenesis. The coenzyme specificities of the two mutants, mXccIDH1 and mXccIDH2, were completely reversed from NAD(+) to NADP(+) , and NADP(+) to NAD(+) , respectively. Furthermore, Ser80 of XccIDH1, and Lys256 and Tyr421 of XccIDH2, were the determinants for the substrate binding. The detailed biochemical properties, such as optimal pH and temperature, thermostability, and metal ion effects, of XccIDH1 and XccIDH2 were further investigated. The possibility of taking the two IDHs into consideration as the targets for drug development to control the plant diseases caused by Xcc 8004 were described and discussed thoroughly. PMID- 27282850 TI - Measuring cardiovascular risk in COPD; child's play or MENSA? PMID- 27282853 TI - Clinical Utility of Potassium-Sparing Diuretics to Maintain Normal Serum Potassium in Peritoneal Dialysis Patients. AB - ? BACKGROUND: Hypokalemia is a vexing problem in end-stage renal disease patients on peritoneal dialysis (PD), and oral potassium supplements (OPS) have limited palatability. Potassium-sparing diuretics (KSD) (spironolactone, amiloride) may be effective in these patients. ? METHODS: We performed a cross-sectional review of 75 current or past (vintage > 6 months) PD patients with regard to serum potassium (K+), OPS, and KSD utilization. We reviewed charts for multiple clinical and laboratory variables, including dialysis adequacy, residual renal function, nutritional status and co-existing medical therapy. ? RESULTS: The cohort was middle-aged with a mean age of 49.2 years (standard deviation [SD] = 14.7) and overweight with a body mass index of 29.5 (6.7) kg/m2. Of all the participants, 57.3% were female, 73.3% African-American, and 48% diabetic with an overall PD vintage of 28.2 (24.3) months at the time of enrollment. Weekly Kt/V was 2.12 (0.43), creatinine clearance was 73.5 (33.6) L/week/1.73 m2 with total daily exchange volume of 10.8 (2.7) L. Residual urine output (RUO) measured at 440 (494) mL (anuric 30.6%). Three-month averaged serum K+ measured at 4 (0.5) mmol/L with 36% of the participants receiving K+ supplements (median: 20 [0;20] mmol/day) and 41.3% KSD (spironolactone dose: 25 - 200 mg/day; amiloride dose: 5 10 mg/day). Serum K+ correlated positively with weekly Kt/V (r = 0.239; p = 0.039), PD vintage (r = 0.272; p = 0.018) but not with PD modality, daily exchange volume, RUO, or KSD use. However, KSD use was associated with decreased use of OPS (r = -0.646; p < 0.0001). ? CONCLUSIONS: Potassium-sparing diuretics were effective in this cohort of PD patients and decreased the need for OPS utilization. PMID- 27282852 TI - The Trio Trial - A Randomized Controlled Clinical Trial Evaluating the Effect of a Biocompatible Peritoneal Dialysis Solution on Residual Renal Function. AB - ? BACKGROUND AND OBJECTIVE: Residual renal function (RRF) correlates with mortality and morbidity rates in patients receiving peritoneal dialysis (PD). We examined the effect of a biocompatible PD solution (Gambrosol Trio; Gambro Lundia AB, Lund, Sweden) with lower concentrations of glucose degradation products on rates of decline in RRF. ? DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Incident patients at 2 centers in Canada and 1 in Hong Kong were randomized (by minimization) in an open-label parallel group trial to receive Gambrosol Trio or standard PD solution (Dianeal; Baxter Healthcare, Mississauga, Canada) for 2 years. Primary outcome was slope of RRF. Secondary outcomes were urine volumes, fluid and nutrition indices, PD and membrane characteristics, peritonitis rates, adverse events, and PD technique survival. ? RESULTS: Residual renal function declined by 0.132 mL/minute/1.73 m(2)/month in 51 patients allocated to biocompatible, and 0.174 mL/minute/1.73 m(2)/month in 50 patients allocated to standard PD solution (difference 0.042 mL/minute/1.73 m(2)/month, p = 0.001). Urine volume, body mass index, normalized protein catabolic rates, and fat mass were higher; total body water, peritoneal ultrafiltration, and D/P creatinine did not differ; and serum phosphate, rates of icodextrin, and automated cycler use were lower with Gambrosol Trio use. There were more peritonitis events with Gambrosol Trio use, while PD technique survival did not differ between groups. ? CONCLUSIONS: The use of the biocompatible PD solution Gambrosol Trio was associated with slower rates of decline in RRF, fluid and nutrition benefits, and increased peritonitis rates. TRIAL NUMBER: ISRCTN26252543. PMID- 27282855 TI - Shortage of Appendicular Skeletal Muscle Is an Independent Risk Factor for Mortality in Peritoneal Dialysis Patients. AB - ? BACKGROUND: Limited data are available on clinical outcomes among peritoneal dialysis patients with shortage of appendicular skeletal muscle (ASM). In this study, we tested the hypothesis that the shortage of ASM is an independent risk factor for mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. ? METHODS: Adult patients undergoing CAPD between March and August 2007 in a single center in China were recruited in this prospective cohort study. Body composition, protein/energy intake, clinical, and biochemical data were collected at baseline, 6 months, and 12 months. End points were all-cause mortality by 12 September 2014. The mean follow-up time was 60.21 (+/- 24.45) months (11.00 - 89.00). ? RESULTS: Compared with the baseline, the mean value of ASM in CAPD patients decreased at 12 months (19.40 +/- 5.60 vs 21.85 +/- 6.14, p < 0.001). According to the estimation of patient survival by Kaplan-Meier, patients with a shortage of ASM had a worse survival rate than those with normal ASM (chi2 = 16.588, p < 0.001). In the Cox's proportional hazards model, patients' survival was independently associated with a shortage of ASM (hazard ratio [HR] = 2.318, p = 0.024, 95% confidence interval [CI] = 1.116 - 4.812). Standard daily protein intake (stDPI) and standard daily energy intake (stDEI) in patients with a shortage of ASM were significantly lower than those in patients with normal ASM in the first follow-up year (t = 2.067, p = 0.041; t = 3.673, p = 0.001). ? CONCLUSIONS: A shortage of ASM is an independent risk factor for mortality in CAPD patients. Further studies are needed to demonstrate that nutritional intervention helps with improving muscle mass and, consequently, the survival of CAPD patients. PMID- 27282856 TI - Hemodialysis is Indicated. PMID- 27282854 TI - A New Method to Increase Ultrafiltration in Peritoneal Dialysis: Steady Concentration Peritoneal Dialysis. AB - ? BACKGROUND: Peritoneal dialysis (PD) has limited power for liquid extraction (ultrafiltration), so fluid overload remains a major cause of treatment failure. ? METHODS: We present steady concentration peritonal dialysis (SCPD), which increases ultrafiltration of PD exchanges by maintaining a constant peritoneal glucose concentration. This is achieved by infusing 50% glucose solution at a constant rate (typically 40 mL/h) during the 4-hour dwell of a 2-L 1.36% glucose exchange. We treated 21 fluid overload episodes on 6 PD patients with high or average-high peritoneal transport characteristics who refused hemodialysis as an alternative. Each treatment consisted of a single session with 1 to 4 SCPD exchanges (as needed). ? RESULTS: Ultrafiltration averaged 653 +/- 363 mL/4 h - twice the ultrafiltration of the peritoneal equilibration test (PET) (300 +/- 251 mL/4 h, p < 0.001) and 6-fold the daily ultrafiltration (100 +/- 123 mL/4 h, p < 0.001). Serum and peritoneal glucose stability and dialysis efficacy were excellent (glycemia 126 +/- 25 mg/dL, peritoneal glucose 1,830 +/- 365 mg/dL, D/P creatinine 0.77 +/- 0.08). The treatment reversed all episodes of fluid overload, avoiding transfer to hemodialysis. Ultrafiltration was proportional to fluid overload (p < 0.01) and inversely proportional to final peritoneal glucose concentration (p < 0.05). ? CONCLUSION: This preliminary clinical experience confirms the potential of SCPD to safely and effectively increase ultrafiltration of PD exchanges. It also shows peritoneal transport in a new dynamic context, enhancing the influence of factors unrelated to the osmotic gradient. PMID- 27282857 TI - Physician Perspectives on Factors Contributing to Readmissions and Potential Prevention Strategies: A Multicenter Survey. AB - BACKGROUND: The transition out of the hospital is a vulnerable time for patients, relying heavily on communication and coordination of resources across care settings. Understanding the perspectives of inpatient and outpatient physicians regarding factors contributing to readmission and potential preventive strategies is crucial in designing appropriately targeted readmission prevention efforts. OBJECTIVE: To examine and compare inpatient and outpatient physician opinions regarding reasons for readmission and interventions that might have prevented readmission. DESIGN: Cross-sectional multicenter study. PARTICIPANTS: We identified patients readmitted to general medicine services within 30 days of discharge at 12 US academic medical centers, and surveyed the primary care physician (PCP), discharging physician from the index admission, and admitting physician from the readmission regarding their endorsement of pre-specified factors contributing to the readmission and potential preventive strategies. MAIN MEASURES: We calculated kappa statistics to gauge agreement between physician dyads (PCP-discharging physician, PCP-admitting physician, and admitting discharging physician). KEY RESULTS: We evaluated 993 readmission events, which generated responses from 356 PCPs (36 % of readmissions), 675 discharging physicians (68 % of readmissions), and 737 admitting physicians (74 % of readmissions). The most commonly endorsed contributing factors by both PCPs and inpatient physicians related to patient understanding and ability to self-manage. The most commonly endorsed preventive strategies involved providing patients with enhanced post-discharge instructions and/or support. Although PCPs and inpatient physicians endorsed contributing factors and potential preventive strategies with similar frequencies, agreement among the three physicians on the specific factors and/or strategies that applied to individual readmission events was poor (maximum kappa 0.30). CONCLUSIONS: Differing opinions among physicians on factors contributing to individual readmissions highlights the importance of communication between inpatient and outpatient providers at discharge to share their different perspectives, and suggests that multi-faceted, broadly applied interventions may be more successful than those that rely on individual providers choosing specific services based on perceived risk factors. PMID- 27282858 TI - Comparative Study of Teachers in Regular Schools and Teachers in Specialized Schools in France, Working with Students with an Autism Spectrum Disorder: Stress, Social Support, Coping Strategies and Burnout. AB - The inclusion of students with Autism Spectrum Disorder (ASD) in schools is a source of stress for teachers. Specialized teachers have, in theory, received special training. To compare the experiences of teachers dealing with students with ASD in different classroom environments. A total of 245 teachers filled out four self-report questionnaires measuring perceived stress, social support, coping strategies, and burnout. Specialized teachers perceive their teaching as a challenge, can count on receiving help from colleagues, use more problem-focused coping strategies and social support seeking behavior, and are less emotionally exhausted than teachers in regular classes. This study highlights that teachers in specialized schools and classes have better adjustment, probably due to their training, experience, and tailored classroom conditions. PMID- 27282859 TI - Automated Quantitation of Spinal CSF Volume and Measurement of Craniospinal CSF Redistribution following Lumbar Withdrawal in Idiopathic Intracranial Hypertension. AB - BACKGROUND AND PURPOSE: Automated methods for quantitation of tissue and CSF volumes by MR imaging are available for the cranial but not the spinal compartment. We developed an iterative method for delineation of the spinal CSF spaces for automated measurements of CSF and cord volumes and applied it to study craniospinal CSF redistribution following lumbar withdrawal in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS: MR imaging data were obtained from 2 healthy subjects and 8 patients with idiopathic intracranial hypertension who were scanned before, immediately after, and 2 weeks after diagnostic lumbar puncture. Imaging included T1-weighted and T2-weighted sequences of the brain and T2-weighted scans of the spine. Repeat scans in 4 subjects were used to assess measurement reproducibility. Whole CNS CSF volumes measured prior to and following lumbar puncture were compared with the withdrawn amounts of CSF. RESULTS: CSF and cord volume measurements were highly reproducible with mean variabilities of -0.7% +/- 1.4% and -0.7% +/- 1.0%, respectively. Mean spinal CSF volume was 77.5 +/- 8.4 mL. The imaging-based pre- to post-CSF volume differences were consistently smaller and strongly correlated with the amounts removed (R = 0.86, P = .006), primarily from the lumbosacral region. These differences are explained by net CSF formation of 0.41 +/- 0.18 mL/min between withdrawal and imaging. CONCLUSIONS: Automated measurements of the craniospinal CSF redistribution following lumbar withdrawal in idiopathic intracranial hypertension reveal that the drop in intracranial pressure following lumbar puncture is primarily related to the increase in spinal compliance and not cranial compliance due to the reduced spinal CSF volume and the nearly unchanged cranial CSF volume. PMID- 27282860 TI - In Vivo 7T MR Quantitative Susceptibility Mapping Reveals Opposite Susceptibility Contrast between Cortical and White Matter Lesions in Multiple Sclerosis. AB - BACKGROUND AND PURPOSE: Magnetic susceptibility measured with quantitative susceptibility mapping has been proposed as a biomarker for demyelination and inflammation in patients with MS, but investigations have mostly been on white matter lesions. A detailed characterization of cortical lesions has not been performed. The purpose of this study was to evaluate magnetic susceptibility in both cortical and WM lesions in MS by using quantitative susceptibility mapping. MATERIALS AND METHODS: Fourteen patients with MS were scanned on a 7T MR imaging scanner with T1-, T2-, and T2*-weighted sequences. The T2*-weighted sequence was used to perform quantitative susceptibility mapping and generate tissue susceptibility maps. The susceptibility contrast of a lesion was quantified as the relative susceptibility between the lesion and its adjacent normal-appearing parenchyma. The susceptibility difference between cortical and WM lesions was assessed by using a t test. RESULTS: The mean relative susceptibility was significantly negative for cortical lesions (P < 10-7) but positive for WM lesions (P < 10-22). A similar pattern was also observed in the cortical (P = .054) and WM portions (P = .043) of mixed lesions. CONCLUSIONS: The negative susceptibility in cortical lesions suggests that iron loss dominates the susceptibility contrast in cortical lesions. The opposite susceptibility contrast between cortical and WM lesions may reflect both their structural (degree of myelination) and pathologic (degree of inflammation) differences, in which the latter may lead to a faster release of iron in cortical lesions. PMID- 27282861 TI - Neuroimaging Wisely. AB - Diagnostic imaging is the most rapidly growing physician service in the Medicare and privately insured population. The growing share of medical costs devoted to imaging procedures has led to increasing concerns among the key federal agencies and private payers. In an attempt to educate health care providers, patients, and families on the importance of making optimal clinical decisions, the American Board of Internal Medicine Foundation organized the Choosing Wisely initiative with strong collaboration from specialty societies representing nearly all medical disciplines. Among 45 tests and treatments listed on the Choosing Wisely Web site, 24 are directly related to imaging. Eleven of the 24 are associated with neuroimaging. The listing of imaging tests in the Choosing Wisely program by multiple medical societies other than the radiology societies acknowledges that appropriate use of medical imaging is a shared responsibility between radiologists and referring physicians. In this article, we highlight why radiologists are uniquely positioned to support the appropriate use of imaging. We review some of the strategies that radiologists can use to help their referring physicians with appropriate ordering of neuroimaging in real-world practice and address some the challenges and pitfalls in implementing patient centered imaging decision-making and shifting to a value-based focus in radiology. PMID- 27282862 TI - White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling. AB - BACKGROUND AND PURPOSE: White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit. MATERIALS AND METHODS: In 185 participants of the Prevention of Dementia by Intensive Vascular Care trial between 72 and 80 years of age with systolic hypertension, white matter hyperintensity volume and CBF were derived from 3D FLAIR and arterial spin-labeling MR imaging, respectively. We compared white matter hyperintensity CBF, normal-appearing white matter CBF, and GM CBF across quartiles of white matter hyperintensity volume and assessed the continuous relation between these CBF estimates and white matter hyperintensity volume by using linear regression. RESULTS: Mean white matter hyperintensity CBF was markedly lower in higher quartiles of white matter hyperintensity volume, and white matter hyperintensity volume and white matter hyperintensity CBF were negatively related (standardized beta = -0.248, P = .001) in linear regression. We found no difference in normal-appearing white matter or GM CBF across quartiles of white matter hyperintensity volume or any relation between white matter hyperintensity volume and normal-appearing white matter CBF (standardized beta = -0.065, P = .643) or GM CBF (standardized beta = -0.035, P = .382) in linear regression. CONCLUSIONS: Higher white matter hyperintensity volume in elderly individuals with hypertension was associated with lower perfusion within white matter hyperintensities, but not with lower perfusion in the surrounding normal-appearing white matter or GM. These findings suggest that white matter hyperintensities in elderly individuals with hypertension relate to local microvascular alterations rather than a general cerebral perfusion deficit. PMID- 27282863 TI - Improved Automatic Detection of New T2 Lesions in Multiple Sclerosis Using Deformation Fields. AB - BACKGROUND AND PURPOSE: Detection of disease activity, defined as new/enlarging T2 lesions on brain MR imaging, has been proposed as a biomarker in MS. However, detection of new/enlarging T2 lesions can be hindered by several factors that can be overcome with image subtraction. The purpose of this study was to improve automated detection of new T2 lesions and reduce user interaction to eliminate inter- and intraobserver variability. MATERIALS AND METHODS: Multiparametric brain MR imaging was performed at 2 time points in 36 patients with new T2 lesions. Images were registered by using an affine transformation and the Demons algorithm to obtain a deformation field. After affine registration, images were subtracted and a threshold was applied to obtain a lesion mask, which was then refined by using the deformation field, intensity, and local information. This pipeline was compared with only applying a threshold, and with a state-of-the-art approach relying only on image intensities. To assess improvements, we compared the results of the different pipelines with the expert visual detection. RESULTS: The multichannel pipeline based on the deformation field obtained a detection Dice similarity coefficient close to 0.70, with a false-positive detection of 17.8% and a true-positive detection of 70.9%. A statistically significant correlation (r = 0.81, P value = 2.2688e-09) was found between visual detection and automated detection by using our approach. CONCLUSIONS: The deformation field based approach proposed in this study for detecting new/enlarging T2 lesions resulted in significantly fewer false-positives while maintaining most true positives and showed a good correlation with visual detection annotations. This approach could reduce user interaction and inter- and intraobserver variability. PMID- 27282851 TI - ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treatment. PMID- 27282864 TI - Bidirectional Changes in Anisotropy Are Associated with Outcomes in Mild Traumatic Brain Injury. AB - BACKGROUND AND PURPOSE: Mild traumatic brain injury results in a heterogeneous constellation of deficits and symptoms that persist in a subset of patients. This prospective longitudinal study identifies early diffusion tensor imaging biomarkers of mild traumatic brain injury that significantly relate to outcomes at 1 year following injury. MATERIALS AND METHODS: DTI was performed on 39 subjects with mild traumatic brain injury within 16 days of injury and 40 controls; 26 subjects with mild traumatic brain injury returned for follow-up at 1 year. We identified subject-specific regions of abnormally high and low fractional anisotropy and calculated mean fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity across all white matter voxels brain-wide and each of several white matter regions. Assessment of cognitive performance and symptom burden was performed at 1 year. RESULTS: Significant associations of brain-wide DTI measures and outcomes included the following: mean radial diffusivity and mean diffusivity with memory; and mean fractional anisotropy, radial diffusivity, and mean diffusivity with health related quality of life. Significant differences in outcomes were found between subjects with and without abnormally high fractional anisotropy for the following white matter regions and outcome measures: left frontal lobe and left temporal lobe with attention at 1 year, left and right cerebelli with somatic postconcussion symptoms at 1 year, and right thalamus with emotional postconcussion symptoms at 1 year. CONCLUSIONS: Individualized assessment of DTI abnormalities significantly relates to long-term outcomes in mild traumatic brain injury. Abnormally high fractional anisotropy is significantly associated with better outcomes and might represent an imaging correlate of postinjury compensatory processes. PMID- 27282866 TI - Vagotomy and subsequent development of diabetes - A nested case-control study. AB - BACKGROUND: Vagal signaling is involved in gastric emptying and the secretion and effect of a number of hormones regulating gluco-metabolic processes and, thus, crucial for metabolic homeostasis. PURPOSE: We hypothesized that vagotomy would increase the risk of developing type 2 diabetes and examined the association between vagotomy and subsequent development of diabetes. METHODS: A nested case control study was conducted with information on cases and controls from the Danish National Patient Registry. Cases included individuals with a diabetes diagnosis subsequent (>12months) to the first registration of vagotomy and/or upper gastrointestinal disease in the period 1977-2011. Controls had no subsequent diagnosis of diabetes and were matched by incidence density sampling, age and gender. Logistic regression analyses were conducted. RESULTS: 501,724 diabetes patients and 1,375,567 matched controls were included in the analysis. Vagotomy was performed on 2772 individuals and 148,489 individuals had an upper gastrointestinal diagnosis. In this combined population, 30,902 were diagnosed with diabetes. The mean follow-up was 16years. The unadjusted odds ratio for developing diabetes following vagotomy was 0.64 (95% confidence interval (CI): 0.58-0.71) and did not change in an adjusted analysis (0.64, 95% CI: 0.58-0.70). When restricting the multivariate-adjusted analysis to patients with type 2 diabetes and type 1 diabetes, respectively, the multivariate odds ratios were 0.79 (95% CI: 0.70-0.89) and 0.75 (95% CI 0.53-1.08), respectively. CONCLUSION: Vagotomy was associated with a significantly decreased risk of developing type 2 diabetes in a population of patients with upper gastrointestinal disease. PMID- 27282865 TI - Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: A randomized, placebo-controlled, crossover study. AB - BACKGROUND: GLP-1 agonists, including liraglutide, have emerged as effective therapies for type 2 diabetes (DM) and obesity. Here, we attempted to delineate how liraglutide, at doses approved for DM, may impact circulating hormones influencing energy homeostasis in diabetics. BASIC PROCEDURES: Using a randomized, placebo-controlled, double-blind, cross-over trial of 20 patients with type 2 diabetes, we examined the effects of liraglutide as compared to placebo on fasting levels of circulating hormones important to energy homeostasis, including leptin, ghrelin, PYY, and GIP. After 17days (0.6mg for 7days, 1.2mg for 7days and 1.8mg for 3days) of treatment, we also studied changes in fMRI responses to food cues. MAIN FINDINGS: By design, to avoid any confounding by weight changes, subjects were studied for 17days, i.e. before body weight changed. Participants on liraglutide had significantly increased GLP-1 levels (p<0.001), decreased percent change in leptin levels (p<0.01) and increased GIP levels (p<0.03) in comparison to placebo treated subjects. Whole brain regressions of functional activity in response to food cues reveal that increased GIP levels were associated with deactivation of the attention- and reward-related insula. Decreases in leptin levels were associated with activations in the reward-related midbrain, precuneus, and dorsolateral prefrontal cortex (DLPFC), and sensorimotor-related motor cortex and with deactivations in the attention-related parietal cortex and the cognitive control related thalamus and pre-SMA. PRINCIPAL CONCLUSIONS: We demonstrate herein short term changes to circulating levels of GIP and leptin in response to GLP-1 agonist liraglutide therapy. These findings suggest that liraglutide may alter the circulating levels of hormones important in energy homeostasis that, in turn, influence CNS perception of food cues. This could possibly lead to compensatory changes in energy homeostasis that could over time limit the efficacy of liraglutide to decrease body weight. These novel findings, which, pointing to the potential advantages of combination therapies, may have therapeutic implications, will need to be confirmed by larger and longer-term trials. PMID- 27282868 TI - Circulating adiponectin and carotid intima-media thickness: A systematic review and meta-analysis. AB - BACKGROUND: Adiponectin (APN) is an adipokine with insulin-sensitizing, anti inflammatory, and vasculoprotective properties. Hypoadiponectinemia has been linked with disease states, such as obesity, type 2 diabetes, and cardiovascular disease. Carotid intima-media thickness (cIMT) is a strong and independent predictor of both coronary and cerebrovascular events, and has been used as a surrogate marker of subclinical atherosclerosis. The aim of this report is to systematically review the evidence on the relationship between APN and cIMT in a wide range of individuals. MATERIALS AND METHODS: Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The "sign test" and "vote count" methods were used to estimate the direction and significance of the relationship between APN and cIMT. The quality of the eligible studies was evaluated using an adapted version of the New Castle Ottawa quality assessment scale. RESULTS: Fifty-five articles fulfilled the inclusion criteria, comprised of only cross-sectional studies, including healthy subjects, general population, and individuals with metabolic, inflammatory, or other chronic diseases. Most associations between APN and cIMT followed a negative direction in the healthier and general populations, and also in cohorts with metabolic disorders and other chronic diseases, but not in those with inflammatory diseases (sign test). These associations were generally found to be weak or non-significant among all cohort groups studied (vote count). CONCLUSION: Our results are suggestive but not conclusive for an inverse association between APN levels and cIMT in diseased and non-diseased populations. PMID- 27282867 TI - Catechol-O-methyltransferase association with hemoglobin A1c. AB - AIMS: Catecholamines have metabolic effects on blood pressure, insulin sensitivity and blood glucose. Genetic variation in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines, is associated with cardiometabolic risk factors and incident cardiovascular disease (CVD). Here we examined COMT effects on glycemic function and type 2 diabetes. METHODS: We tested whether COMT polymorphisms were associated with baseline HbA1c in the Women's Genome Health Study (WGHS), and Meta-Analyses of Glucose and Insulin related traits Consortium (MAGIC), and with susceptibility to type 2 diabetes in WGHS, DIAbetes Genetics Replication And Meta-analysis consortium (DIAGRAM), and the Diabetes Prevention Program (DPP). Given evidence that COMT modifies some drug responses, we examined association with type 2 diabetes and randomized metformin and aspirin treatment. RESULTS: COMT rs4680 high-activity G-allele was associated with lower HbA1c in WGHS (beta=-0.032% [0.012], p=0.008) and borderline significant in MAGIC (beta=-0.006% [0.003], p=0.07). Combined COMT per val allele effects on type 2 diabetes were significant (OR=0.98 [0.96-0.998], p=0.03) in fixed-effects analyses across WGHS, DIAGRAM, and DPP. Similar results were obtained for 2 other COMT SNPs rs4818 and rs4633. In the DPP, the rs4680 val allele was borderline associated with lower diabetes incidence among participants randomized to metformin (HR=0.81 [0.65-1.00], p=0.05). CONCLUSIONS: COMT rs4680 high-activity G-allele was associated with lower HbA1c and modest protection from type 2 diabetes. The directionality of COMT associations was concordant with those previously observed for cardiometabolic risk factors and CVD. PMID- 27282869 TI - Obesity development in neuron-specific lipoprotein lipase deficient mice is not responsive to increased dietary fat content or change in fat composition. AB - We have previously reported that mice with neuron-specific LPL deficiency (NEXLPL /-) become obese by 16weeks of age on chow. Moreover, these mice had reduced uptake of triglyceride (TG)-rich lipoprotein-derived fatty acids and lower levels of n-3 long chain polyunsaturated fatty acids (n-3 PUFAs) in the hypothalamus. Here, we asked whether increased dietary fat content or altered dietary composition could modulate obesity development in NEXLPL-/- mice. Male NEXLPL-/- mice and littermate controls (WT) were randomly assigned one of three synthetic diets; a high carbohydrate diet (HC, 10% fat), a high-fat diet (HF, 45% fat), or a HC diet supplemented with n-3 PUFAs (HCn-3, 10% fat, Lovaza, GSK(r)). After 42weeks of HC feeding, body weight and fat mass were increased in the NEXLPL-/- mice compared to WT. WT mice fed a HF diet displayed typical diet-induced obesity, but weight gain was only marginal in HF-fed NEXLPL-/- mice, with no significant difference in body composition. Dietary n-3 PUFA supplementation did not prevent obesity in NEXLPL-/- mice, but was associated with differential modifications in hypothalamic gene expression and PUFA concentration compared to WT mice. Our findings suggest that neuronal LPL is involved in the regulation of body weight and composition in response to either the change in quantity (HF feeding) or quality (n-3 PUFA-enriched) of dietary fat. The precise role of LPL in lipid sensing in the brain requires further investigation. PMID- 27282870 TI - Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients. AB - OBJECTIVE: To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. METHODS: Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. RESULTS: Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p<0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p<0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p<0.05) and increased by overfeeding (p<0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p<0.05) but this was independent of the insulin signal. CONCLUSION: Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. PMID- 27282871 TI - Efficient hydrogen evolution in transition metal dichalcogenides via a simple one step hydrazine reaction. AB - Hydrogen evolution reaction is catalysed efficiently with precious metals, such as platinum; however, transition metal dichalcogenides have recently emerged as a promising class of materials for electrocatalysis, but these materials still have low activity and durability when compared with precious metals. Here we report a simple one-step scalable approach, where MoOx/MoS2 core-shell nanowires and molybdenum disulfide sheets are exposed to dilute aqueous hydrazine at room temperature, which results in marked improvement in electrocatalytic performance. The nanowires exhibit ~100 mV improvement in overpotential following exposure to dilute hydrazine, while also showing a 10-fold increase in current density and a significant change in Tafel slope. In situ electrical, gate-dependent measurements and spectroscopic investigations reveal that hydrazine acts as an electron dopant in molybdenum disulfide, increasing its conductivity, while also reducing the MoOx core in the core-shell nanowires, which leads to improved electrocatalytic performance. PMID- 27282872 TI - Frequency and intensity of alcohol consumption: new evidence from Sweden. AB - There is an increasing body of evidence that the intensity in which alcohol is drunk is of greater concern than the frequency or overall quantity consumed. This paper provides an extensive analysis of the demand for alcohol as measured by total quantity, frequency, and intensity. A unique large sample of cross sectional data from Sweden 2004-2011 allows reduced-form alcohol demand equations to be estimated for beer, wine, and spirits, split by alcohol drinking pattern (average vs. binge drinkers) and gender. Results find a negative beer excise rate effect for participation and frequency, and positive effect for intensity. The effect was stronger for binge drinkers. Generally, the results also show a positive socioeconomic (income and education) gradient in frequency demand and a negative gradient in the intensity demand. Female wine drinkers show a positive socioeconomic gradient in both frequency and intensity. The findings highlight the complexity of this policy space. Tax increases appear to reduce frequency but raise intensity consumed. The more educated and higher earners drink more in total, but less intensely when they do and this is likely to explain in part why poor health is concentrated amongst lower socioeconomic status individuals. PMID- 27282873 TI - Response to the letter to the editor: Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration. PMID- 27282874 TI - Intolerant contact lens wearers exhibit ocular surface impairment despite 3 months wear discontinuation. AB - PURPOSE: To evaluate ocular surface (OS) parameters recovery in intolerant contact lens (CL) wearers after a period of discontinuation. METHODS: This is a retrospective analysis of data from 87 intolerant CL wearers who had discontinued their use for an average period of 12 weeks because of associated discomfort and failure to successfully refit. Data were collected from clinical charts. Data from 50 matched healthy volunteers served as controls. Clinical tests included subjective discomfort symptoms questionnaire (Ocular Surface Disease Index, OSDI), Schirmer test, break-up time (BUT), corneal esthesiometry and corneo conjunctival staining. Laboratory tests included scraping and imprint cytology. Tear protein analysis included dosage of total tear protein (TP), lysozyme-C (LYS C), lactoferrin (LACTO), zinc-alpha2-glycoprotein (ZAG-2), IgA heavy chain bands (Ig-A), and serum albumin (ALB). Data were correlated to wear parameters. RESULTS: All values were significantly worse in intolerant CL wearers group (p always <0.001). In particular, lower values compared to controls were found for BUT, corneal esthesiometry, goblet cell density, LYS-C, LACTO, ZAG-2, and TP. On the contrary, higher values compared to controls were found for OSDI, staining, imprint cytology, scraping cytology, ALB, IgA-heavy chain. The IgA/LYS-C ratio calculated as an index of the increased activity of the IgA-producing cell was found significantly higher in the intolerant group and in correlation with discomfort symptoms. CONCLUSIONS: Ocular surface parameters were altered in intolerant CL wearers, even after a prolonged discontinuation period. Our data suggest that OS recovery necessary to successfully refit lenses may need a discontinuation time longer than 3 months. PMID- 27282875 TI - Unexpected complications related to tamponade after vitrectomy. PMID- 27282876 TI - Fast neutron-induced structural rearrangements at a soybean NAP1 locus result in gnarled trichomes. AB - KEY MESSAGE: Three adjacent and distinct sequence rearrangements were identified at a NAP1 locus in a soybean mutant. Genetic dissection and validation revealed the function of this gene in soybean trichome development. A soybean (Glycine max (L.) Merr.) gnarled trichome mutant, exhibiting stunted trichomes compared to wild-type, was identified in a fast neutron mutant population. Genetic mapping using whole genome sequencing-based bulked segregant analysis identified a 26.6 megabase interval on chromosome 20 that co-segregated with the phenotype. Comparative genomic hybridization analysis of the mutant indicated that the chromosome 20 interval included a small structural variant within the coding region of a soybean ortholog (Glyma.20G019300) of Arabidopsis Nck-Associated Protein 1 (NAP1), a regulator of actin nucleation during trichome morphogenesis. Sequence analysis of the candidate allele revealed multiple rearrangements within the coding region, including two deletions (approximately 1-2 kb each), a translocation, and an inversion. Further analyses revealed that the mutant allele perfectly co-segregated with the phenotype, and a wild-type soybean NAP1 transgene functionally complemented an Arabidopsis nap1 mutant. In addition, mapping and exon sequencing of NAP1 in a spontaneous soybean gnarled trichome mutant (T31) identified a frame shift mutation resulting in a truncation of the coding region. These data indicate that the soybean NAP1 gene is essential for proper trichome development and show the utility of the soybean fast neutron population for forward genetic approaches for identifying genes. PMID- 27282877 TI - Correlates for psycho-active substance use among boarding secondary school adolescents in Enugu, South East, Nigeria. AB - BACKGROUND: Psycho-active substance use among adolescents is a national and global problem and its attendant effects on adolescents cannot be overemphasized. The objectives of this study are to determine the prevalence and pattern of psychoactive substance use among adolescents; the substances involved and the extent of the problem in this locale. METHODS: This is a cross-sectional study that assesses the pattern of psychoactive substance use among secondary school adolescents in Enugu, south East, Nigeria. The study was carried out among adolescents attending six secondary boarding schools in Enugu metropolis of Enugu State of Nigeria. The WHO Student Drug Use Questionnaire was adapted for this study. Data were analyzed using the Statistical Package for Social Sciences program (SPSS), version 17. Chi-square and multivariate regression were used as a test of significance for qualitative variables. A p-value less than 0.05 were accepted as significant for each statistical test. RESULTS: Out of 900, a total of 896 respondents, comprising 400 and 82 boys (482) (53.8 %) and 400 and 14 girls (414) (46.2 %) completed the questionnaires. This gave a response rate of 99.6 %. The study revealed that the prevalence of current use for psychoactive substances ranges from 0.4 to 34.9 % while that for life use ranges from 0.8 to 63.5 %. The least being cannabis and the most being kola nuts. Kola nut is the most widely used psychoactive substance both for current use, past year use and the respondents' life time use. It shows a lifetime prevalence of 63.5 % and a current use prevalence of 34.9 %. More than half of the users of each of the psychoactive substances take it occasionally, using them on 1-5 days in a month. On the other hand, almost one-quarter of the users of each of the substances take it on 20 or more days in a month. CONCLUSION: The study revealed that the prevalence of current use for psychoactive substances ranges from 0.4 to 34.9 % while that for life use ranges from 0.8 to 63.5 %. The least being cannabis and the most being kola nuts. PMID- 27282878 TI - Portal hypertensive gastropathy after variceal eradication: more bleeding risk or just more reddening? PMID- 27282879 TI - Interferon-free treatment for HCV-infected patients with decompensated cirrhosis. AB - Progress in interferon-free treatment against hepatitis C virus (HCV) has remained a challenge in patients with decompensated cirrhosis due to a paucity of information on efficacy and safety profiles. This review illustrates that interferon-free treatment could result in greater than 85 % sustained virological response (SVR) rates in patients with HCV genotype 1 and decompensated cirrhosis. The combination of pangenotypic HCV NS5A inhibitor velpatasvir and HCV NS5B inhibitor sofosbuvir has demonstrated high SVR rates in patients with HCV genotypes 1, 2, 3, 4 or 6 and decompensated cirrhosis. Certain patients discontinued treatment due to adverse events, death or having liver transplantation. Taken together, interferon-free treatment could produce higher SVR rates in decompensated hepatic cirrhosis. However, as adverse events were occasionally observed, liver transplantation should always be considered as well. Further improvements in treatment are called for in patients with decompensated cirrhosis. PMID- 27282880 TI - Estimating the annual volume of hematologic cancer cases per hematologist oncologist in the United States: are we treating rare cancers too rarely? PMID- 27282881 TI - Steroid receptor RNA activator: Biologic function and role in disease. AB - Steroid receptor RNA activator (SRA) is a type of long noncoding RNA (lncRNA) which coordinates the functions of various transcription factors, enhances steroid receptor-dependent gene expression, and also serves as a distinct scaffold. The novel, profound and expanded roles of SRA are emerging in critical aspects of coactivation of nuclear receptors (NRs). As a nuclear receptor coactivator, SRA can coactivate androgen receptor (AR), estrogen receptor alpha (ERalpha), ERbeta, progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptor and retinoic acid receptor (RAR). Although SRA is one of the least well-understood molecules, increasing studies have revealed that SRA plays a key role in both biological processes, such as myogenesis and steroidogenesis, and pathological changes, including obesity, cardiomyopathy, and tumorigenesis. Furthermore, the SRA-related signaling pathways, such as the mitogen-activated protein kinase (p38 MAPK), Notch and tumor necrosis factor alpha (TNFalpha) pathways, play critical roles in the pathogenesis of estrogen dependent breast cancers. In addition, the most recent data demonstrates that SRA expression may serve as a new prognostic marker in patients with ER-positive breast cancer. Thus, elucidating the molecular mechanisms underlying SRA-mediated functions is important to develop proper novel strategies to target SRA in the diagnosis and treatment of human diseases. PMID- 27282882 TI - Distinct properties of proteases and nucleases in the gut, salivary gland and saliva of southern green stink bug, Nezara viridula. AB - Stink bugs negatively impact numerous plant species of agricultural and horticultural importance. While efforts to develop effective control measures are underway, the unique digestive physiology of these pests presents a significant hurdle for either protein- or nucleotide-based management options. Here we report the comparative biochemical and proteomic characterization of proteases and nucleases from the gut, salivary gland and saliva of the southern green stink bug, Nezara viridula. The pH optimum for protease activity was acidic (5 to 6) in the gut with the primary proteases being cysteine proteases, and alkaline (8 to 9) in the saliva and salivary gland with the primary proteases being serine proteases. The serine proteases in saliva differ biochemically from trypsin and chymotrypsin, and the cathepsins in the gut and saliva showed distinct properties in inhibitor assays. Nuclease activity (DNase, RNase, dsRNase) was concentrated in the salivary gland and saliva with negligible activity in the gut. The most abundant proteins of the gut (530) and salivary gland (631) identified by proteomic analysis included four gut proteases along with eight proteases and one nuclease from the salivary gland. Understanding of N. viridula digestive physiology will facilitate the design of new strategies for management of this significant pest. PMID- 27282883 TI - Molecular characterization of KMT2A fusion partner genes in 13 cases of pediatric leukemia with complex or cryptic karyotypes. AB - In pediatric acute leukemias, reciprocal chromosomal translocations frequently cause gene fusions involving the lysine (K)-specific methyltransferase 2A gene (KMT2A, also known as MLL). Specific KMT2A fusion partners are associated with the disease phenotype (lymphoblastic vs. myeloid), and the type of KMT2A rearrangement also has prognostic implications. However, the KMT2A partner gene cannot always be identified by banding karyotyping. We sought to identify such partner genes in 13 cases of childhood leukemia with uninformative karyotypes by combining molecular techniques, including multicolor banding FISH, reverse transcriptase PCR, and long-distance inverse PCR. Of the KMT2A fusion partner genes, MLLT3 was present in five patients, all with acute lymphoblastic leukemia, MLLT1 in two patients, and MLLT10, MLLT4, MLLT11, and AFF1 in one patient each. Reciprocal reading by long-distance inverse PCR also disclosed KMT2A fusions with PITPNA in one patient, with LOC100132273 in another patient, and with DNA sequences not compatible with any gene in three patients. The most common KMT2A breakpoint region was intron/exon 9 (3/8 patients), followed by intron/exon 11 and 10. Finally, multicolor banding revealed breakpoints in other chromosomes whose biological and prognostic implications remain to be determined. We conclude that the combination of molecular techniques used in this study can efficiently identify KMT2A fusion partners in complex pediatric acute leukemia karyotypes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27282885 TI - Using mHealth as a Lever to Promote Mental Health Care Quality Through Patient Engagement. PMID- 27282884 TI - Mental Health Nursing Education: An Instructor's View. AB - If you knew no one with a mental illness, what would mold your perceptions of someone with a mental illness? A movie character, a television actor, a description from a friend? Each of these explanations has been given to me by nursing students beginning their mental health nursing clinical rotation. Reconsideration of the limited amount of mental health education in nursing school is urgent. As we become more engrossed as a society in television and movies, the result appears to be a deceptive idea of what true mental illness entails. This piece shares personal insight from a mental health nursing educator and the transformation she witnesses in her students after a mental health clinical rotation. PMID- 27282886 TI - Modification of the Secondary Binding Site of Xylanases Illustrates the Impact of Substrate Selectivity on Bread Making. AB - To investigate the importance of substrate selectivity for xylanase functionality in bread making, the secondary binding site (SBS) of xylanases from Bacillus subtilis (XBS) and Pseudoalteromonas haloplanktis was modified. This resulted in two xylanases with increased relative activity toward water-unextractable wheat arabinoxylan (WU-AX) compared to water-extractable wheat arabinoxylan, i.e., an increased substrate selectivity, without changing other biochemical properties. Addition of both modified xylanases in bread making resulted in increased loaf volumes compared to the wild types when using weak flour. Moreover, maximal volume increase was reached at a lower dosage of the mutant compared to wild-type XBS. The modified xylanases were able to solubilize more WU-AX and decreased the average degree of polymerization of soluble arabinoxylan in dough more during fermentation. This possibly allowed for additional water release, which might be responsible for increased loaf volumes. Altered SBS functionality and, as a result, enhanced substrate selectivity most probably caused these differences. PMID- 27282887 TI - The effect of an automated point of care tool on diagnosis and management of childhood obesity in primary care. AB - BACKGROUND: Childhood obesity is underdiagnosed in primary care practices. Our study aimed to compare rates of documentation of diagnosis of obesity and counselling for nutrition and physical activity at an academic primary care practice prior to and following implementation of a body mass index (BMI)-based electronic point of care clinical reminder tool. METHODS: We performed a retrospective record review of children aged 2-18 years undergoing well child visits during any of three calendar years (2009, 2011 and 2013). The electronic clinical reminder tool was implemented in September 2010. Records of children with BMI > 95th percentile were electronically searched for terms of documentation of diagnosis of obesity and nutrition and physical activity counselling. Multivariable logistic regression models were used to adjust for potential patient and provider confounders. RESULTS: Among those with BMI >= 95th percentile, there was a statistically significant increase in documentation of diagnosis of obesity (45.5% in 2009 vs. 52.4% in 2011; P < 0.001; adjusted odds ratio 1.36; 95% CI 1.13-1.65) and in counselling for physical activity and nutrition (66.8% in 2009 vs. 75.2% in 2011; P < 0.001; adjusted odds ratio 1.33; 95% CI 1.06-1.66) following implementation of the tool. Compared with 2011, there was no statistically significant increase in documentation of obesity (50.4%) or nutrition and physical activity counselling (77.9%) in 2013. CONCLUSIONS: The implementation of a point of care clinical reminder tool was associated with improvement in documentation of diagnosis of obesity and counselling for nutrition and physical activity. Further studies are needed to determine the impact of these automated tools on weight outcomes in children. PMID- 27282888 TI - Impact of the induced organic anion transporter 1 (Oat1) renal expression by furosemide on the pharmacokinetics of organic anions. AB - AIM: Furosemide is a loop diuretic. Different authors demonstrated that continuous administration of furosemide modulates the expression of organic anion transporters. This study was undertaken to simultaneously evaluate the effects of furosemide pretreatment on organic anion transporter 1 (Oat1) and multidrug resistance protein 2 (Mrp2) renal expressions, on p-aminohippurate (PAH) pharmacokinetics and on renal and urinary PAH levels in rats. METHODS: Male Wistar rats were treated with furosemide (6 mg/100 g body weight per day, subcutaneously, 4 days) (treated group) or saline (control group). On the fifth day, PAH was administered as a bolus infusion in the femoral vein, and plasma samples were obtained from femoral artery at different time points. PAH levels in renal tissue and urine were also assessed. Renal Oat1 and Mrp2 expressions were evaluated by western blotting. RESULTS: Furosemide pretreatment increased both the expression of Oat1 and Mrp2. PAH plasma concentrations decreased following a biexponential function. The furosemide-treated group showed higher PAH plasma levels, a lower systemic clearance and elimination rate constant from the peripheral compartment, indicating that PAH renal elimination was decreased. PAH levels in renal tissue were significantly elevated and in urine appeared to be significantly lower as compared with control animals. CONCLUSIONS: Furosemide pretreatment caused a significant decrease of PAH renal elimination, despite Oat1 and Mrp2 augmented renal expression. The goal of the present study is the addition of important information in the wide gap of knowledge that exists about drug-drug interactions. Because of furosemide worldwide use, the data obtained are interesting and useful in terms of translation to clinical practice. PMID- 27282889 TI - Reduction of bacteria and human immunodeficiency virus Type 1 infectivity of platelet suspension in plasma using xenon flash-pulse light in a bench-scale trial. AB - BACKGROUND: Current pathogen reduction systems for platelet concentrates (PCs) require addition of chemical compounds and/or reduction of plasma content in PCs. We have investigated a new method using xenon (Xe) flash-pulse light without additional compounds or plasma replacement. STUDY DESIGN AND METHODS: An aliquot of apheresis platelets (PLTs) in plasma inoculated with bacteria or human immunodeficiency virus Type 1 (HIV-1) was irradiated with Xe flash-pulse light (Xe flash phototreatment). Bacterial growth was monitored up to 6 days of storage, whereas HIV-1 infectivity was assayed just after treatment. Pairs of Xe flash-phototreated and untreated PCs were examined for PLT lesion during the storage period. RESULTS: Under the current conditions, a low titer (1.8 colony forming units [CFUs]/mL) of Staphylococcus aureus did not proliferate during the 6-day storage period, but grew in some cases at high-titer (24.0 CFUs/mL) inoculation. HIV-1 infectivity was reduced by 1.8 log. PLT recovery of the treated PCs was lower than untreated ones. An increase of mean PLT volume and glucose consumption, together with a decrease of hypotonic shock response and pH, were enhanced by the treatment. CD62P- and PAC-1-positive PLTs increased after the treatment, indicating the induction of PLT activation. Among biologic response modifiers, soluble CD40 ligand was significantly increased in the treated PCs on Day 6. CONCLUSIONS: Xe flash phototreatment could prevent bacterial proliferation and reduce HIV-1 infectivity in 100% plasma PCs without any additional compounds, but enhanced PLT storage lesions. Further improvement is required to increase the potency of pathogen inactivation with reducing PLT damage. PMID- 27282890 TI - A wearable headset for monitoring electromyography responses within spinal surgery. AB - PURPOSE: This research examines an approach for enhancing the efficiency of spinal surgery utilising the technological capabilities and design functionalities of wearable headsets, in this case Google Glass. The aim was to improve the efficiency of the selective dorsal rhizotomy neurosurgical procedure initially through the use of Glass via an innovative approach to information design for an intraoperative monitoring display. METHODS: Utilising primary and secondary research methods the development of a new electromyography response display for a wearable headset was undertaken. RESULTS: Testing proved that Glass was fit for purpose and that the new intraoperative monitor design provided an example platform for the innovative intraoperative monitoring display; however, alternative wearable headsets such as the Microsoft HoloLens could also be equally viable. CONCLUSION: The new display design combined with the appropriate wearable technology could greatly benefit the selective dorsal rhizotomy procedure. PMID- 27282891 TI - Comparison of medetomidine-morphine and medetomidine-methadone for sedation, isoflurane requirement and postoperative analgesia in dogs undergoing laparoscopy. AB - OBJECTIVE: To compare the effects of intravenous (IV) medetomidine-morphine and medetomidine-methadone on preoperative sedation, isoflurane requirements and postoperative analgesia in dogs undergoing laparoscopic surgery. STUDY DESIGN: Randomized, crossover trial. ANIMALS: Twelve adult Beagle dogs weighing 15.1 +/- 4.1 kg. METHODS: Dogs were administered medetomidine (2.5 MUg kg-1) IV 5 minutes before either methadone (MET) or morphine (MOR) (0.3 mg kg-1) IV. Anaesthesia was induced with propofol, maintained with isoflurane in oxygen, and depth was clinically assessed and adjusted by an anaesthetist blinded to the treatment. Animals underwent laparoscopic abdominal biopsies. Sedation and nausea scores, pulse rate (PR), respiratory rate (fR), noninvasive systolic arterial blood pressure (SAP), rectal temperature (RT) and pain scores were recorded before drug administration, 5 minutes after medetomidine injection and 10 minutes after opioid administration. Propofol dose, PR, fR, SAP, oesophageal temperature (TOES), end-tidal carbon dioxide and end-tidal isoflurane concentration (Fe'Iso) were recorded intraoperatively. Pain scores, PR, fR, SAP and RT were recorded 10 minutes after extubation, every hour for 6 hours, then at 8, 18 and 24 hours. The experiment was repeated with the other drug 1 month later. RESULTS: Nine dogs completed the study. After opioid administration and intraoperatively, PR, but not SAP, was significantly lower in MET. Fe'Iso was significantly lower in MET. Temperature decreased in both treatments. Pain scores were significantly higher in MOR at 3 hours after extubation, but not at other time points. Two dogs required rescue analgesia; one with both treatments and one in MOR. CONCLUSION AND CLINICAL RELEVANCE: At the dose used, sedation produced by both drugs when combined with medetomidine was equivalent, while volatile anaesthetic requirements and PR perioperatively were lower with methadone. Postoperative analgesia was deemed to be adequate for laparoscopy with either protocol, although methadone provided better analgesia 3 hours after surgery. PMID- 27282892 TI - Stent Coating Integrity of Durable and Biodegradable Coated Drug Eluting Stents. AB - BACKGROUND: Coatings consisting of a polymer and drug are widely used in drug eluting stents (DES) and are essential in providing programmable drug release kinetics. Among other factors, stent coating technologies can influence blood compatibility, affect acute and sub-acute healing, and potentially trigger a chronic inflammatory response. OBJECTIVE: The aim of this study was to investigate the short-term (7 and 28 days) and long-term (90 and 180 days) coating integrity of the Xience Prime Everolimus-Eluting Stent (EES), Resolute Zotarolimus-Eluting Stent (ZES), Taxus Paclitaxel-Eluting Stent (PES), and Nobori Biolimus A9-Eluting Stent (BES) in a rabbit ilio-femoral stent model. METHODS AND RESULTS: Stented arteries (n = 48) were harvested and the tissue surrounding the implanted stents digested away with an enzymatic solution. Results demonstrated that the majority of struts of EES were without any coating defects with a few struts showing minor defects. Similarly, for the ZES, most of the struts were without coating defects at all time points except at 180 days. The majority of PES demonstrated mostly webbing and uneven coating. In the BES group, the majority of strut coating showed polymer cracking. CONCLUSION: Overall, the EES and ZES had fewer coating defects than the PES and BES. Coating defects, however increase over time for the ZES, whereas the percent of coating irregularities remained constant for the EES. These results provide, for the first time, a comparison of the long-term durability of these drug-eluting stent coatings in vivo. PMID- 27282893 TI - The Development of Therapeutics for Peripheral Artery Disease: A Unique Cardiovascular Risk Population. PMID- 27282894 TI - Dual Antiplatelet Therapy in the Prevention of Recurrent Ischemic Events. PMID- 27282896 TI - The Natural History of Thoracic Aortic Disease: So Much Left to Learn. PMID- 27282895 TI - Aortic Dissection in Patients With Genetically Mediated Aneurysms: Incidence and Predictors in the GenTAC Registry. AB - BACKGROUND: Aortic dissection (AoD) is a serious complication of thoracic aortic aneurysm (TAA). Relative risk for AoD in relation to TAA etiology, incidence, and pattern after prophylactic TAA surgery are poorly understood. OBJECTIVES: This study sought to determine the incidence, pattern, and relative risk for AoD among patients with genetically associated TAA. METHODS: The population included adult GenTAC participants without AoD at baseline. Standardized core laboratory tests classified TAA etiology and measured aortic size. Follow-up was performed for AoD. RESULTS: Bicuspid aortic valve (BAV) (39%) and Marfan syndrome (MFS) (22%) were the leading diagnoses in the studied GenTAC participants (n = 1,991). AoD occurred in 1.6% over 3.6 +/- 2.0 years; 61% of AoD occurred in patients with MFS. Cumulative AoD incidence was 6-fold higher among patients with MFS (4.5%) versus others (0.7%; p < 0.001). MFS event rates were similarly elevated versus those in patients with BAV (0.3%; p < 0.001). AoD originated in the distal arch or descending aorta in 71%; 52% of affected patients, including 68% with MFS, had previously undergone aortic grafting. In patients with proximal aortic surgery, distal aortic size (descending thoracic, abdominal aorta) was larger among patients with AoD versus those without AoD (both p < 0.05), whereas the ascending aorta size was similar. Conversely, in patients without previous surgery, aortic root size was greater in patients with subsequent AoD (p < 0.05), whereas distal aortic segments were of similar size. MFS (odds ratio: 7.42; 95% confidence interval: 3.43 to 16.82; p < 0.001) and maximal aortic size (1.86 per cm; 95% confidence interval: 1.26 to 2.67; p = 0.001) were independently associated with AoD. Only 4 of 31 (13%) patients with AoD had pre-dissection images that fulfilled size criteria for prophylactic TAA surgery at a subsequent AoD site. CONCLUSIONS: Among patients with genetically associated TAA, MFS augments risk for AoD even after TAA grafting. Although increased aortic size is a risk factor for subsequent AoD, events typically occur below established thresholds for prophylactic TAA repair. PMID- 27282897 TI - Diagnosis and Treatment Algorithm for Blood Flow Obstructions in Patients With Left Ventricular Assist Device. AB - BACKGROUND: Thrombosis is an uncommon, but severe complication of left ventricular assist devices (LVADs). OBJECTIVES: This study analyzed experience with obstruction of blood flow through the LVAD with the purpose of developing optimal diagnosis and treatment of LVAD-related thrombosis. METHODS: Between October 2009 and July 2015, a total of 652 LVAD were implanted in 557 patients. Blood flow abnormalities in patients with LVAD (n = 524) were identified and classified as "high-power" and "low-flow" events. RESULTS: Three types of late blood flow obstructions were identified: 1) pre-pump via thrombus obstructing the inflow cannula (26 events; 0.037 events per patient-year); 2) intra-pump (70 events; 0.1 events per patient-year); and 3) post-pump via thrombosis of the outflow graft or stenosis of the anastomosis to the aorta (4 events; 0.006 events per patient-year). Pre-pump obstruction was treated by washout maneuver in 9 cases (success rate, 100%), thrombolysis in 9 patients (success rate, 56%), and pump exchange in 9 cases (success rate, 100%); 1 patient died without treatment and 2 were weaned from LVAD. Intra-pump obstruction was treated by thrombolysis (n = 9; success rate, 33%), pump exchange (n = 53; success rate, 94%), and removal due to myocardial recovery (n = 3; success rate, 100%); 7 patients died without treatment and parameters spontaneously normalized in 2 cases. Post-pump obstruction was treated in 2 patients by stenting (success rate, 100%), and was left untreated in 2 cases. CONCLUSIONS: We identified 3 types of LVAD-related blood flow obstruction, and developed an algorithm for optimal diagnosis and treatment. PMID- 27282898 TI - Managing VAD Complications: Our Growth Industry. PMID- 27282899 TI - Invasive FFR and Noninvasive CFR in the Evaluation of Ischemia: What Is the Future? AB - This review provides an integrative and forward-looking perspective on the gamut of coronary physiology for the diagnosis and management of atherosclerosis. Because clinical events serve as the ultimate gold standard, the future of all diagnostic tests, including invasive fractional flow reserve and noninvasive coronary flow reserve, depends on their ability to improve patient outcomes. Given the prominent role of acute coronary syndromes and invasive procedures in cardiology, we practically consider 2 broad categories of patients with coronary disease: acute and stable. For patients with acute coronary disease, coronary physiology may potentially refine treatment of the culprit lesion. For both patients with stable and acute nonculprit disease, reducing hard endpoints with revascularization potentially occurs at the severe end of the focal physiological spectrum, an area under-represented in existing trials. Nonepicardial disease and diffuse atherosclerosis remain underexplored aspects of coronary physiology for testing of novel treatments. PMID- 27282900 TI - Procedure Logging in Interventional Cardiology Training Curriculum: The Interventional Fellows' T-Score. PMID- 27282901 TI - Electronic Cigarette Smoking Increases Aortic Stiffness and Blood Pressure in Young Smokers. PMID- 27282902 TI - Treatment of Pure Aortic Regurgitation Using a Second-Generation Transcatheter Aortic Valve Implantation System. PMID- 27282903 TI - Long-QT Syndrome, Brugada Syndrome, and Catecholaminergic Polymorphic Ventricular Tachycardia: A Tale of 3 Diseases. PMID- 27282904 TI - Reply: Long-QT Syndrome, Brugada Syndrome, and Catecholaminergic Polymorphic Ventricular Tachycardia: A Tale of 3 Diseases : Ibutilide as a Torsade de Pointes Stress Test. PMID- 27282905 TI - Ibutilide as a Torsade de Pointes Stress Test. PMID- 27282906 TI - No Utility of the Wearable Cardioverter-Defibrillator in Patients With Nonischemic Cardiomyopathy? PMID- 27282908 TI - Correction. PMID- 27282907 TI - Reply: No Utility of the Wearable Cardioverter-Defibrillator in Patients With Nonischemic Cardiomyopathy? PMID- 27282909 TI - Correction. PMID- 27282911 TI - Morphological, ultrastructural and functional imaging of frozen/thawed and vitrified/warmed human ovarian tissue retrieved from oncological patients. AB - STUDY QUESTION: Which is the best method for human ovarian tissue cryopreservation: slow freezing/rapid thawing (SF/RT) or vitrification/warming (V/W)? SUMMARY ANSWER: The conventional SF/RT protocol used in this study seems to better preserve the morpho-functional status of human cryopreserved ovarian tissue than the used open carrier V/W protocol. WHAT IS KNOWN ALREADY: Cryopreservation of human ovarian tissue is generally performed using the SF/RT method. However, reduction in the follicular pool and stroma damage are often observed. An emerging alternative procedure is represented by V/W which seems to allow the maintenance of the morphological integrity of the stroma. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study including six patients affected by oncological diseases and enrolled from January to December 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian tissue was laparoscopically harvested from the right and left ovaries and was cryopreserved using a routinary SF/RT protocol or a V/W method, involving tissue incubation in two solutions (containing propylene glycol, ethylene glycol and sucrose at different concentrations) and vitrification in an open system. For each patient, three pieces from each ovary were collected at the time of laparoscopy (fresh tissue) and after storage (SF/RT or V/W) and processed for light microscopy (LM) and transmission electron microscopy (TEM), to assess the morphological and ultrastructural features of follicles and stroma, and for laser scanning confocal microscopy (LSCM), to determine the functional energetic/redox stroma status. The preservation status of SF/RT and V/W ovarian tissues was compared with that of fresh ones, as well as between them. MAIN RESULTS AND THE ROLE OF CHANCE: By LM and TEM, SF/RT and V/W samples showed cryodamage of small entity. Interstitial oedema and increased stromal cell vacuolization and chromatin clumping were observed in SF/RT samples; in contrast, V/W samples showed oocyte nuclei with slightly thickened chromatin and irregular shapes. The functional imaging analysis by LSCM revealed that the mitochondrial activity and intracellular reactive oxygen species levels were reduced both in SF/RT and in V/W samples compared with fresh samples. The study also showed progressive dysfunction of the mitochondrial activity going from the outer to the inner serial section of the ovarian cortex. The reduction of mitochondrial activity of V/W samples compared with fresh samples was significantly higher in the inner section than in the outer section. LIMITATIONS, REASONS FOR CAUTION: The results report the bioenergetic and oxidative status assessment of fresh and cryopreserved human ovarian tissue by LSCM, a technique recently applied to tissue samples. The use of LSCM on human ovarian tissues after SF/RT or V/W is a new application that requires validation. The procedures for mitochondrial staining with functional probes and fixing are not yet standardized. Xenografting of the cryopreserved ovarian tissue in severe combined immunodeficient mice and in vitro culture have not yet been performed. WIDER IMPLICATIONS OF THE FINDINGS: The identification of a cryopreservation method able to maintain the morpho-functional integrity of the ovarian tissue and a number of follicles comparable with those observed in fresh tissue might optimize results in clinical practice, in terms of recovery, duration of ovarian function and increased delivery outcomes after replanting. The SF/RT protocol allowed better morpho-functional tissue integrity than the V/W procedure. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by Fondazione del Monte di Bologna e Ravenna, Italy. Dr N.A.M. was granted by the project ONEV MIUR PONa3 00134-n.254/R&C 18 5 2011 and the project GR-2011-02351396 (Ministry of Health, Young Researchers Grant 2011/2012). There are no competing interests. TRIAL REGISTRATION NUMBER: Clinical trial 74/2001/0 (approved:13 2 2002): 'Pilot study on cryopreservation of human ovarian tissue: morphological and immunohistochemical analysis before and after cryopreservation'. PMID- 27282912 TI - Synthesis of GPR40 targeting 3 H- and 18 F-probes towards selective beta cell imaging. AB - Diabetes affects an increasing number of patients worldwide and is responsible for a significant rise in healthcare expenses. Imaging of beta-cells in vivo is expected to contribute to an improved understanding of the underlying pathophysiology, improved diagnosis, and development of new treatment options for diabetes. Here, we describe the first radiosyntheses of [3 H]-TAK875 and [18 F] TAK875 derivatives to be used as beta-cell imaging probes addressing the free fatty acid receptor 1 (FFAR1/GPR40). The fluorine-labeled derivative showed similar agonistic activity as TAK875 in a functional assay. The radiosynthesis of the 18 F-labelled tracer 2a was achieved with 16.7 +/- 5.7% radiochemical yield in a total synthesis time of 60-70 min. PMID- 27282913 TI - Conjunctival fibrous histiocytoma in an 8-year-old boy. AB - An 8-year-old healthy boy underwent surgery for excision of a painless, enlarging vascularized conjunctival tumor. Histopathology disclosed a mass comprised of interweaving spindle cells and scattered histiocytes in a fibrous matrix, consistent with benign fibrous histiocytoma. This rare tumor can resemble several conditions, including scleritis/episcleritis, inflamed pterygium, juvenile xanthogranuloma, foreign body granuloma, solitary fibrous tumor, amelanotic melanoma, and squamous cell carcinoma. PMID- 27282915 TI - Sequential treatment strategy for malignant pleural effusion in non-small cell lung cancer with the activated epithelial grow factor receptor mutation. AB - With the advent of molecularly targeted therapy, it is necessary to reconsider the strategy for malignant pleural effusion in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The aim of this study was to evaluate the efficacy of a two-line sequential treatment strategy in this patient subgroup. First-line treatment was gefitinib (250 mg/day) until disease progression. Second-line treatment was thoracoscopic talc pleurodesis followed by chemotherapy. Primary endpoints were the overall response and progression-free survival rates after first-line treatment, and the overall survival rate after first- and second-line treatment. Secondary endpoints were the success rate of thoracoscopic talc pleurodesis and gefitinib toxicity. Among the 76 patients enrolled, 61 (80%) were female and the median age was 62 years. The overall response rate after first-line treatment was 92.1% and median progression-free survival was 15 months. The success rate for thoracoscopic talc pleurodesis in 33 patients was 94%. Median follow-up was 35 months. Median overall survival was 39 months. The 1- and 3-year overall survival rates were 86.4% and 46.1%, respectively. The two-line sequential treatment strategy enhanced survival. These preliminary findings provide an insight into novel therapeutic models for malignant pleural effusion in NSCLC harbouring EGFR mutations. PMID- 27282916 TI - Erratum to: Trans effects of chromosome aneuploidies on DNA methylation patterns in human Down syndrome and mouse models. PMID- 27282910 TI - MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics. AB - Glioblastoma multiforme (GBM) is the most common and lethal cancer of the adult brain, remaining incurable with a median survival time of only 15 months. In an effort to identify new targets for GBM diagnostics and therapeutics, recent studies have focused on molecular phenotyping of GBM subtypes. This has resulted in mounting interest in microRNAs (miRNAs) due to their regulatory capacities in both normal development and in pathological conditions such as cancer. miRNAs have a wide range of targets, allowing them to modulate many pathways critical to cancer progression, including proliferation, cell death, metastasis, angiogenesis, and drug resistance. This review explores our current understanding of miRNAs that are differentially modulated and pathologically involved in GBM as well as the current state of miRNA-based therapeutics. As the role of miRNAs in GBM becomes more well understood and novel delivery methods are developed and optimized, miRNA-based therapies could provide a critical step forward in cancer treatment. PMID- 27282914 TI - Altered excitatory-inhibitory balance within somatosensory cortex is associated with enhanced plasticity and pain sensitivity in a mouse model of multiple sclerosis. AB - BACKGROUND: Chronic neuropathic pain is a common symptom of multiple sclerosis (MS). MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) has been used as an animal model to investigate the mechanisms of pain in MS. Previous studies have implicated sensitization of spinal nociceptive networks in the pathogenesis of pain in EAE. However, the involvement of supraspinal sites of nociceptive integration, such as the primary somatosensory cortex (S1), has not been defined. We therefore examined functional, structural, and immunological alterations in S1 during the early stages of EAE, when pain behaviors first appear. We also assessed the effects of the antidepressant phenelzine (PLZ) on S1 alterations and nociceptive (mechanical) sensitivity in early EAE. PLZ has been shown to restore central nervous system (CNS) tissue concentrations of GABA and the monoamines (5-HT, NA) in EAE. We hypothesized that PLZ treatment would also normalize nociceptive sensitivity in EAE by restoring the balance of excitation and inhibition (E-I) in the CNS. METHODS: We used in vivo flavoprotein autofluorescence imaging (FAI) to assess neural ensemble responses in S1 to vibrotactile stimulation of the limbs in early EAE. We also used immunohistochemistry (IHC), and Golgi-Cox staining, to examine synaptic changes and neuroinflammation in S1. Mechanical sensitivity was assessed at the clinical onset of EAE with Von Frey hairs. RESULTS: Mice with early EAE exhibited significantly intensified and expanded FAI responses in S1 compared to controls. IHC revealed increased vesicular glutamate transporter (VGLUT1) expression and disrupted parvalbumin+ (PV+) interneuron connectivity in S1 of EAE mice. Furthermore, peri-neuronal nets (PNNs) were significantly reduced in S1. Morphological analysis of excitatory neurons in S1 revealed increased dendritic spine densities. Iba-1+ cortical microglia were significantly elevated early in the disease. Chronic PLZ treatment was found to normalize mechanical thresholds in EAE. PLZ also normalized S1 FAI responses, neuronal morphologies, and cortical microglia numbers and attenuated VGLUT1 reactivity-but did not significantly attenuate the loss of PNNs. CONCLUSIONS: These findings implicate a pro excitatory shift in the E-I balance of the somatosensory CNS, arising early in the pathogenesis EAE and leading to large-scale functional and structural plasticity in S1. They also suggest a novel antinociceptive effect of PLZ treatment. PMID- 27282917 TI - Micromonospora ureilytica sp. nov., Micromonospora noduli sp. nov. and Micromonospora vinacea sp. nov., isolated from Pisum sativum nodules. AB - A diversity study on the presence of strains representing the genus Micromonospora in Pisum sativum nodules collected from Canizal (Spain) has provided evidence of the high number of isolates that might represent novel species. In the present work, we have characterized three of these isolates: GUI23T, GUI43T and GUI63T. Phenotypic and genotypic analyses confirmed that all strains represent novel species of the genus Micromonospora with the following proposed names: Micromonospora ureilytica sp. nov., type strain GUI23T (=CECT 9022T=DSM 101692T), Micromonospora noduli sp. nov., type strain GUI43T (=CECT 9020T=DSM 101694T), and Micromonospora vinacea sp. nov., type strain GUI63T (=CECT 9019T=DSM 101695T). PMID- 27282918 TI - Quality of life of nursing home residents in China: A mediation analysis. AB - We examined whether the relationship between activities of daily living and quality of life was mediated by depression, and identified differences of the mediating effects by age group. In this cross-sectional survey, 231 older adults were recruited from eight nursing homes. The path analysis indicated that depression played an important mediating role in the relationship between activities of daily living and quality of life. Depression appeared to be more significant for the mental health component as an outcome compared to the physical health component of quality of life. The impact of depression as a mediator for the older old group was greater than the young-middle group. This finding increases our understanding of the impact of age on the mediating effect of depression on the relationship between activities of daily living and quality of life. Healthcare providers should consider older adults' age differences when integrating physical or depression programs into clinical practice to enhance quality of life. PMID- 27282919 TI - Environmental risk factors contributing to traffic accidents in children: a case control study. AB - The aim of this study is to identify environmental risk factors related to road accidents in children of Tehran. This case-control study was performed in 2013. The cases were injured pedestrians aged 5-15 who were admitted to major hospitals supervised by Tehran University of Medical Sciences. The sample size for the cases was 273 and for the control group was 546. For the completeness of the clusters, 7 extra persons in case (total = 280) and 14 persons (total = 560) in control group were included. The interference of confounding variables assessed through forward conditional logistic regression. Result shows occurrence of traffic accidents was significantly associate with the width of the alleys or (<5 m: OR = 8.4, 95% CI: 3.3-21.5; 5-8 m: OR = 4.7, 95% CI: 1.8-12.2), distance from home to school((<100 m: OR = 1.7, 95% CI: 1.0-2.8), existence of parking lot (OR = 1.5, 95% CI: 1.0-2.3), traffic congestion (OR = 4.1, 95% CI: 2.6-6.4), traffic speed (OR = 2.1, 95% CI: 1.3-3.2) and existence of pedestrian bridges(OR = 4.2, 95% CI: 2.6-6.8). In the light of the important role of environmental factors in the occurrence of child traffic accidents, alleviating structural risk factors in addition to education and enforcement need more systematic efforts and planning by policymakers and urban planners to attain pedestrian safety goals. PMID- 27282920 TI - Comparative leaf proteomics of drought-tolerant and -susceptible peanut in response to water stress. AB - Water stress (WS) predisposes peanut plants to fungal infection resulting in pre harvest aflatoxin contamination. Major changes during water stress including oxidative stress, lead to destruction of photosynthetic apparatus and other macromolecules within cells. Two peanut cultivars with diverse drought tolerance characteristics were subjected to WS, and their leaf proteome was compared using two-dimensional electrophoresis complemented with MALDI-TOF/TOF mass spectrometry. Ninety-six protein spots were differentially abundant to water stress in both cultivars that corresponded to 60 non-redundant proteins. Protein interaction prediction analysis suggests that 42 unique proteins showed interactions in tolerant cultivar while 20 showed interactions in the susceptible cultivar, activating other proteins in directed system response networks. Four proteins: glutamine ammonia ligase, chitin class II, actin isoform B, and beta tubulin, involved in metabolism, defense and cellular biogenesis, are unique in tolerant cultivar and showed positive interactions with other proteins. In addition, four proteins: serine/threonine protein phosphate PP1, choline monooxygenase, peroxidase 43, and SNF1-related protein kinase regulatory subunit beta-2, that play a role as cryoprotectants through signal transduction, were induced in drought tolerant cultivar following WS. Eleven interologs of these proteins were found in Arabidopsis interacting with several proteins and it is believed that similar mechanisms/pathways exist in peanut. SIGNIFICANCE: Peanuts (Arachis hypogaea L.) are a major source of plant protein grown in subtropical and tropical regions of the world. Pre-harvest aflatoxin contamination is a major problem that affects peanut crop yield and food safety. Poor understanding of molecular and cellular mechanisms associated with aflatoxin resistance is largely responsible for the lack of progress in elucidating a process/methodology for reducing aflatoxin contamination in peanuts. Drought perturbs the invasion of the aflatoxin producing fungus and thus affects the quality and yield of peanut. Therefore, more studies involving the effects of drought stress to determine the molecular changes will enhance our understanding of the key metabolic pathways involved in the combined stresses. The changes associated with the biotic and abiotic interactions within the peanut will be used to determine the metabolic pathways involved in the stress tolerance. This research would be beneficial in identifying the tolerant molecular signatures and promoting food safety and consumer health through breeding superior quality peanut cultivars. PMID- 27282922 TI - Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the "bivalent" Sea Snake Antivenom. AB - Recent advances in proteomics enable deep profiling of the compositional details of snake venoms for improved understanding on envenomation pathophysiology and immunological neutralization. In this study, the venom of Australian tiger snake (Notechis scutatus) was trypsin-digested in solution and subjected to nano-ESI LCMS/MS. Applying a relative quantitative proteomic approach, the findings revealed a proteome comprising 42 toxin subtypes clustered into 12 protein families. Phospholipases A2 constitute the most abundant toxins (74.5% of total venom proteins) followed by Kunitz serine protease inhibitors (6.9%), snake venom serine proteases (5.9%), alpha-neurotoxins (5.6%) and several toxins of lower abundance. The proteome correlates with N. scutatus envenoming effects including pre-synaptic and post-synaptic neurotoxicity and consumptive coagulopathy. The venom is highly lethal in mice (intravenous median lethal dose=0.09MUg/g). BioCSL Sea Snake Antivenom, raised against the venoms of beaked sea snake (Hydrophis schistosus) and N. scutatus (added for enhanced immunogenicity), neutralized the lethal effect of N. scutatus venom (potency=2.95mg/ml) much more effectively than the targeted H.schistosus venom (potency=0.48mg/ml). The combined venom immunogen may have improved the neutralization against phospholipases A2 which are abundant in both venoms, but not short-neurotoxins which are predominant only in H. schistosus venom. SIGNIFICANCE: A shotgun proteomic approach adopted in this study revealed the compositional details of the venom of common tiger snake from Australia, Notechis scutatus. The proteomic findings provided additional information on the relative abundances of toxins and the detection of proteins of minor expression unreported previously. The potent lethal effect of the venom was neutralized by bioCSL Sea Snake Antivenom, an anticipated finding due to the fact that the Sea Snake Antivenom is actually bivalent in nature, being raised against a mix of venoms of the beaked sea snake (Hydrophis schistosus) and N. scutatus. However, it is surprising to note that bioCSL Sea Snake Antivenom neutralized N. scutatus venom much more effectively compared to the targeted sea snake venom by a marked difference in potency of approximately 6-fold. This phenomenon may be explained by the main difference in the proteomes of the two venoms, where H. schistosus venom is dominated by short-neurotoxins in high abundance - this is a poorly immunogenic toxin group that has been increasingly recognized in the venoms of a few cobras. Further investigations should be directed toward strategies to improve the neutralization of short-neurotoxins, in line with the envisioned production of an effective pan-regional elapid antivenom. PMID- 27282921 TI - Improvement of core-fucosylated glycoproteome coverage via alternating HCD and ETD fragmentation. AB - Core-fucosylation (CF) plays important roles in regulating biological processes in eukaryotes. Alterations of CF-glycosites or CF-glycans in bodily fluids correlate with cancer development. Therefore, global research of protein core fucosylation with an emphasis on proteomics can explain pathogenic and metastasis mechanisms and aid in the discovery of new potential biomarkers for early clinical diagnosis. In this study, a precise and high throughput method was established to identify CF-glycosites from human plasma. We found that alternating HCD and ETD fragmentation (AHEF) can provide a complementary method to discover CF-glycosites. A total of 407 CF-glycosites among 267 CF glycoproteins were identified in a mixed sample made from six normal human plasma samples. Among the 407 CF-glycosites, 10 are without the N-X-S/T/C consensus motif, representing 2.5% of the total number identified. All identified CF glycopeptide results from HCD and ETD fragmentation were filtered with neutral loss peaks and characteristic ions of GlcNAc from HCD spectra, which assured the credibility of the results. This study provides an effective method for CF glycosites identification and a valuable biomarker reference for clinical research. BIOLOGICAL SIGNIFICANCE: CF-glycosytion plays an important role in regulating biological processes in eukaryotes. Alterations of the glycosites and attached CF-glycans are frequently observed in various types of cancers. Thus, it is crucial to develop a strategy for mapping human CF-glycosylation. Here, we developed a complementary method via alternating HCD and ETD fragmentation (AHEF) to analyze CF-glycoproteins. This strategy reveals an excellent complementarity of HCD and ETD in the analysis of CF-glycoproteins, and provides a valuable biomarker reference for clinical research. PMID- 27282923 TI - Hypocholesterolemic and Anticarcinogenic Effect of Vicia faba Protein Hydrolyzates. AB - In recent years, the consumption of vegetal-source proteins has been studied to determine their preventing effect on the development of several chronic diseases. The initial purpose of this report was to determine the effect of a hypercholesterolemic diet (HCD) given to mice, alone or with azoxymethane (AOM), on various obesity biochemical biomarkers, as well as on the induction of colon aberrant crypts (aberrant crypt foci; ACF). At the end of the 5-week assay, animals fed the HCD showed alterations in the level of total cholesterol, high- and low-density lipoproteins, and in the Atherogenic Index; besides, a significant elevation was observed in the number of ACF. Our second aim was to examine the effect of a Faba Protein Hydrolyzate (FPH) on mice fed the HCD. We first obtained protein hydrolyzates from the seeds of Vicia faba, determined the in vitro antioxidant potential with two tests, and, subsequently, evaluated the effect on obesity biomarkers and on the number of ACF. In the first case, we found that, generally, the best protective effect was obtained with the low dose of FPH (10 mg/kg) administered to animals fed the HCD, and injected AOM. With respect to the number of ACF, we observed that this dose was more effective, inhibiting such lesions to almost the level determined for the normocholesterolemic diet (NCD). Therefore, our results demonstrated the relevance of a HCD to develop anomalies in obesity biomarkers in mouse, as well as to increase the number of precarcinogenic lesions. Our results also showed a protective response with the administration of FPH, particularly with a specific dose, suggesting the need for extending research on the matter by widening the spectra of doses, in order to clearly define its potential to counteract the damage induced by the HCD, as well as to confirm if antioxidation in mice was involved in such an effect. PMID- 27282925 TI - Leisure-Time Physical Activity in Pregnancy and Maternal-Child Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Cohort Studies. AB - BACKGROUND: Evidence suggests that leisure-time physical activity (LTPA) during pregnancy is associated with a reduced risk of preeclampsia, gestational diabetes mellitus (GDM), and preterm birth. However, these results are inconsistent when comparing cohort studies and randomized controlled trials (RCTs). OBJECTIVE: The purpose of our study was to compare the associations between LTPA in pregnancy and maternal (GDM, preeclampsia, and weight gain during pregnancy) and child health outcomes (preterm birth, birthweight, and fetal growth) between RCTs and cohort studies. METHODS: We performed a systematic search in PubMed, Web of Science, and EBSCO up to 31 August 2015. Inclusion criteria for experimental studies required randomized trials with a control group and exposure to a physical activity structured program. The inclusion criteria for cohort studies required information on LTPA during pregnancy as an exposure and at least one maternal-child health outcome. We assessed the methodological quality of all studies and performed a meta-analysis to produce summary estimates of the effects using random models. RESULTS: We included 30 RCTs and 51 cohort studies. The meta analysis of RCTs indicated that participation in LTPA was associated with lower weight gain during pregnancy, lower likelihood of GDM, and lower likelihood of delivering a large-for-gestational-age infant. Cohort studies indicated that participation in LTPA was associated with lower weight gain during pregnancy, lower likelihood of GDM, and lower risk of preterm delivery. CONCLUSIONS: Our findings support the promotion of LTPA in pregnancy as a strategy to improve maternal and child health. PMID- 27282924 TI - Skeletal muscle fibroblasts in health and disease. AB - As the primary producer of extracellular matrix (ECM) proteins in skeletal muscle, fibroblasts play an important role providing structural support to muscle. Skeletal muscle ECM is vital for force transduction from muscle cells to tendons and bones to create movement. It is these ECM connections that allow the movement created in muscle to be transmitted to our skeleton. This review discusses how fibroblasts participate in maintaining this healthy ECM within skeletal muscle. Additionally, from a basic science perspective, we discuss current methods to identify and study skeletal muscle fibroblasts, as this is critical to bettering our understanding of these important cells. Finally, skeletal muscle fibrosis is discussed, which is a devastating clinical condition characterized by an overproduction of ECM within skeletal muscle. We discuss the role that fibroblasts and other cells play in muscle fibrosis as well as the implications of this work. PMID- 27282927 TI - Erratum: Phosphoprotein network analysis of white adipose tissues unveils deregulated pathways in response to high-fat diet. PMID- 27282926 TI - Peptic Ulcer and Exercise. AB - Relationships between peptic ulcer and physical activity have as yet received little attention. The prevalence of ulceration is high in racehorses and sled dogs, particularly during periods of competition. In humans, some occupational comparisons show an increased risk among manual workers, but it remains difficult to separate effects of work-related activity from social class and attendant influences of smoking, excessive alcohol consumption, shift work, and other stressors. Two studies of leisure activity point to some benefit from moderate physical activity, one finding a reduced risk of gastric ulcers and the other finding no effect on gastric ulcers but a reduced risk of duodenal ulcers in men only. Moderate physical activity could have a favorable impact on a number of risk factors for peptic ulceration. It could reduce gastric secretions and enhance immune function, with the latter reducing the risk of Helicobacter pylori infection. Moderate activity might also reduce anxiety and encourage the adoption of a healthy lifestyle, with avoidance of smoking and an excessive consumption of alcohol. However, prolonged endurance exercise seems likely to have a negative impact, suppressing immune function, reducing mucosal blood flow, and calling for frequent administration of non-steroidal anti-inflammatory drugs (NSAIDs). As with other aspects of exercise medicine, there may be a J-shaped relationship between dose and response. Limited human observations suggest a favourable response to bouts of moderate leisure activity but little benefit from heavy occupational activity and, in some animal studies, negative effects at high volumes and intensities of exercise. Further research is recommended to confirm the nature of this relationship, clarify the location of any nadir of risk for various classes of individual, and to explore mechanisms and antidotes. PMID- 27282928 TI - Engineering integrated photonics for heralded quantum gates. AB - Scaling up linear-optics quantum computing will require multi-photon gates which are compact, phase-stable, exhibit excellent quantum interference, and have success heralded by the detection of ancillary photons. We investigate the design, fabrication and characterisation of the optimal known gate scheme which meets these requirements: the Knill controlled-Z gate, implemented in integrated laser-written waveguide arrays. We show device performance to be less sensitive to phase variations in the circuit than to small deviations in the coupler reflectivity, which are expected given the tolerance values of the fabrication method. The mode fidelity is also shown to be less sensitive to reflectivity and phase errors than the process fidelity. Our best device achieves a fidelity of 0.931 +/- 0.001 with the ideal 4 * 4 unitary circuit and a process fidelity of 0.680 +/- 0.005 with the ideal computational-basis process. PMID- 27282929 TI - Defining the neuroanatomic basis of motor coordination in children and its relationship with symptoms of attention-deficit/hyperactivity disorder. AB - BACKGROUND: When children have marked problems with motor coordination, they often have problems with attention and impulse control. Here, we map the neuroanatomic substrate of motor coordination in childhood and ask whether this substrate differs in the presence of concurrent symptoms of attention deficit/hyperactivity disorder (ADHD). METHOD: Participants were 226 children. All completed Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)-based assessment of ADHD symptoms and standardized tests of motor coordination skills assessing aiming/catching, manual dexterity and balance. Symptoms of developmental coordination disorder (DCD) were determined using parental questionnaires. Using 3 Tesla magnetic resonance data, four latent neuroanatomic variables (for the cerebral cortex, cerebellum, basal ganglia and thalamus) were extracted and mapped onto each motor coordination skill using partial least squares pathway modeling. RESULTS: The motor coordination skill of aiming/catching was significantly linked to latent variables for both the cerebral cortex (t = 4.31, p < 0.0001) and the cerebellum (t = 2.31, p = 0.02). This effect was driven by the premotor/motor cortical regions and the superior cerebellar lobules. These links were not moderated by the severity of symptoms of inattention, hyperactivity and impulsivity. In categorical analyses, the DCD group showed atypical reduction in the volumes of these regions. However, the group with DCD alone did not differ significantly from those with DCD and co morbid ADHD. CONCLUSIONS: The superior cerebellar lobules and the premotor/motor cortex emerged as pivotal neural substrates of motor coordination in children. The dimensions of these motor coordination regions did not differ significantly between those who had DCD, with or without co-morbid ADHD. PMID- 27282930 TI - Polymorphism of IL-10 gene promoter region: association with T cell proliferative responses after acellular pertussis vaccination in adults. AB - Individual variation in immune responses is always encountered after vaccination. This phenomenon is also seen after acellular pertussis vaccination. The aim of this present study was to investigate whether single nucleotide polymorphisms (SNPs) in the IL-10 gene promoter region (rs1800890, rs1800896, rs1800871), IL 12B (rs2546890), IL-12RB1 (rs372889), IL-17A (rs2275913), and IL-23R (rs11209026) affect the immune responses after acellular pertussis vaccination. The T cell proliferative response was evaluated in 38 Finnish young adults who received a second booster dose of a vaccine combination of diphtheria, tetanus, and acellular pertussis, 10 years after the previous booster. The response was evaluated with a proliferation assay in which vaccine antigens pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were used for the stimulation, before and 1 month after the second vaccination. Specific proliferation of peripheral blood mononuclear cells against pertussis antigens was affected by IL-10 SNP in the promoter region at position -1082 (A>G, rs1800896). One month after the vaccination, subjects with the AA and AG genotypes had a significantly higher T cell proliferative response against PT and FHA compared to those with the GG genotype. Subjects with the GG genotype had the lowest responses. As a conclusion, our preliminary results indicate that IL-10 SNP -1082 might play an important role in T cell-mediated immune responses after acellular pertussis vaccination. PMID- 27282932 TI - A Framework for Predicting Intraspecific Variation in Plant Defense. AB - One of the most well-supported theories regarding the evolution of plant defenses is the resource availability hypothesis (RAH). RAH posits that species from high resource environments grow fast and allocate little to herbivore-resistance traits, whereas those species in low-resource environments grow slow and are highly resistant to herbivores. However, within species, how resources influence defense is unclear and existing theories make opposing predictions. Here, we review studies documenting intraspecific variation in plant defense across resource gradients and find little support for RAH. We outline why RAH does not apply intraspecifically and present a predictive framework for understanding how resources influence intraspecific variation in plant defense. Our framework provides an important step towards reconciling inter- versus intraspecific strategies of defense. PMID- 27282931 TI - Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells. AB - Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4 Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID- 27282933 TI - Slingshot feeding of the goblin shark Mitsukurina owstoni (Pisces: Lamniformes: Mitsukurinidae). AB - Five striking and prey capture events of two goblin sharks were videotaped at sea for the first time, showing their extraordinary biting process. The goblin sharks swung their lower jaw downward and backward to attain a huge gape and then rapidly protruded the jaws forward a considerable distance. The jaws were projected at a maximum velocity of 3.1 m/s to 8.6-9.4% of the total length of the shark, which is by far the fastest and greatest jaw protrusion among sharks. While the jaws were being retracted, the mouth opened and closed again, which was considered a novel feeding event for sharks. Phylogenetic evidence suggested that their feeding behavior has evolved as an adaptation to food-poor deep-sea environments, possibly as a trade-off for the loss of strong swimming ability. PMID- 27282935 TI - Phosphate-a poison for humans? AB - Maintenance of phosphate balance is essential for life, and mammals have developed a sophisticated system to regulate phosphate homeostasis over the course of evolution. However, due to the dependence of phosphate elimination on the kidney, humans with decreased kidney function are likely to be in a positive phosphate balance. Phosphate excess has been well recognized as a critical factor in the pathogenesis of mineral and bone disorders associated with chronic kidney disease, but recent investigations have also uncovered toxic effects of phosphate on the cardiovascular system and the aging process. Compelling evidence also suggests that increased fibroblastic growth factor 23 and parathyroid hormone levels in response to a positive phosphate balance contribute to adverse clinical outcomes. These insights support the current practice of managing serum phosphate in patients with advanced chronic kidney disease, although definitive evidence of these effects is lacking. Given the potential toxicity of excess phosphate, the general population may also be viewed as a target for phosphate management. However, the widespread implementation of dietary phosphate intervention in the general population may not be warranted due to the limited impact of increased phosphate intake on mineral metabolism and clinical outcomes. Nonetheless, the increasing incidence of kidney disease or injury in our aging society emphasizes the potential importance of this issue. Further work is needed to more completely characterize phosphate toxicity and to establish the optimal therapeutic strategy for managing phosphate in patients with chronic kidney disease and in the general population. PMID- 27282934 TI - EWS-FLI1 impairs aryl hydrocarbon receptor activation by blocking tryptophan breakdown via the kynurenine pathway. AB - Ewing sarcoma (ES) is an aggressive pediatric tumor driven by the fusion protein EWS-FLI1. We report that EWS-FLI1 suppresses TDO2-mediated tryptophan (TRP) breakdown in ES cells. Gene expression and metabolite analyses reveal an EWS-FLI1 dependent regulation of TRP metabolism. TRP consumption increased in the absence of EWS-FLI1, resulting in kynurenine and kynurenic acid accumulation, both aryl hydrocarbon receptor (AHR) ligands. Activated AHR binds to the promoter region of target genes. We demonstrate that EWS-FLI1 knockdown results in AHR nuclear translocation and activation. Our data suggest that EWS-FLI1 suppresses autocrine AHR signaling by inhibiting TDO2-catalyzed TRP breakdown. PMID- 27282936 TI - Preventing peritoneal membrane fibrosis in peritoneal dialysis patients. AB - Long-term peritoneal dialysis causes morphologic and functional changes in the peritoneal membrane. Although mesothelial-mesenchymal transition of peritoneal mesothelial cells is a key process leading to peritoneal fibrosis, and bioincompatible peritoneal dialysis solutions (glucose, glucose degradation products, and advanced glycation end products or a combination) are responsible for altering mesothelial cell function and proliferation, mechanisms underlying these processes remain largely unclear. Peritoneal fibrosis has 2 cooperative parts, the fibrosis process itself and the inflammation. The link between these 2 processes is frequently bidirectional, with each one inducing the other. This review outlines our current understanding about the definition and pathophysiology of peritoneal fibrosis, recent studies on key fibrogenic molecular machinery in peritoneal fibrosis, such as the role of transforming growth factor-beta/Smads, transforming growth factor-beta beta/Smad independent pathways, and noncoding RNAs. The diagnosis of peritoneal fibrosis, including effluent biomarkers and the histopathology of a peritoneal biopsy, which is the gold standard for demonstrating peritoneal fibrosis, is introduced in detail. Several interventions for peritoneal fibrosis based on biomarkers, cytology, histology, functional studies, and antagonists are presented in this review. Recent experimental trials in animal models, including pharmacology and gene therapy, which could offer novel insights into the treatment of peritoneal fibrosis in the near future, are also discussed in depth. PMID- 27282937 TI - Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. AB - Immune checkpoint inhibitors (CPIs), monoclonal antibodies that target inhibitory receptors expressed on T cells, represent an emerging class of immunotherapy used in treating solid organ and hematologic malignancies. We describe the clinical and histologic features of 13 patients with CPI-induced acute kidney injury (AKI) who underwent kidney biopsy. Median time from initiation of a CPI to AKI was 91 (range, 21 to 245) days. Pyuria was present in 8 patients, and the median urine protein to creatinine ratio was 0.48 (range, 0.12 to 0.98) g/g. An extrarenal immune-related adverse event occurred prior to the onset of AKI in 7 patients. Median peak serum creatinine was 4.5 (interquartile range, 3.6-7.3) mg/dl with 4 patients requiring hemodialysis. The prevalent pathologic lesion was acute tubulointerstitial nephritis in 12 patients, with 3 having granulomatous features, and 1 thrombotic microangiopathy. Among the 12 patients with acute tubulointerstitial nephritis, 10 received treatment with glucocorticoids, resulting in complete or partial improvement in renal function in 2 and 7 patients, respectively. However, the 2 patients with acute tubulointerstitial nephritis not given glucocorticoids had no improvement in renal function. Thus, CPI-induced AKI is a new entity that presents with clinical and histologic features similar to other causes of drug-induced acute tubulointerstitial nephritis, though with a longer latency period. Glucocorticoids appear to be a potentially effective treatment strategy. Hence, AKI due to CPIs may be caused by a unique mechanism of action linked to reprogramming of the immune system, leading to loss of tolerance. PMID- 27282939 TI - Solomon A, Fahey JL, Malmgren RA. Immunohistologic localization of gamma-1 macroglobulins, beta-2A-myeloma proteins, 6.6 S gamma-myeloma proteins and Bence Jones proteins. Blood. 1963;21(4):403-423. PMID- 27282938 TI - Vaccination with recombinant RgpA peptide protects against Porphyromonas gingivalis-induced bone loss. AB - OBJECTIVE: Following Porphyromonas gingivalis infection in mice, the efficacy of vaccination by recombinant and native RgpA in modulating the early local anti inflammatory and immune responses and periodontal bone loss were examined. MATERIAL AND METHODS: Using the subcutaneous chamber model, exudates were analyzed for cytokines after treatment with native RgpA and adjuvant (test), or adjuvant and saline alone (controls). Mice were also immunized with recombinant RgpA after being orally infected with P. gingivalis. After 6 wk, serum was examined for anti-P. gingivalis IgG1 and IgG2a titers and for alveolar bone resorption. RESULTS: Immunization with native RgpA shifted the immune response toward an anti-inflammatory response as demonstrated by decreased proinflammatory cytokine IL-1beta production and greater anti-inflammatory cytokine IL-4 in chamber exudates. Systemically, immunization with recombinant RgpA peptide prevented alveolar bone loss by 50%, similar to immunization with heat-killed whole bacteria. Furthermore, recombinant RgpA shifted the humoral response toward high IgG1 and low IgG2a titers, representing an in vivo anti-inflammatory response. CONCLUSIONS: The present study demonstrates the potential of RgpA to shift the early local immune response toward an anti-inflammatory response while vaccination with recRgpA protected against P. gingivalis-induced periodontitis. PMID- 27282940 TI - Platelet disorders: the next generation is in. PMID- 27282941 TI - The identity crisis of Hif-1alpha in HSC biology. PMID- 27282942 TI - BRAF inhibitor: targeted therapy in hairy cell leukemia. PMID- 27282943 TI - Novel NF-kappaB regulator in ABC DLBCL. PMID- 27282944 TI - Enhancing cytotoxicity of immunotoxins in AML. PMID- 27282945 TI - VWF, ADAMTS13, and acute coronary syndromes. PMID- 27282947 TI - Development of immune organs and functioning in humans and test animals: Implications for immune intervention studies. AB - A healthy immune status is mostly determined during early life stages and many immune-related diseases may find their origin in utero and the first years of life. Therefore, immune health optimization may be most effective during early life. This review is an inventory of immune organ maturation events in relation to developmental timeframes in minipig, rat, mouse and human. It is concluded that time windows of immune organ development in rodents can be translated to human, but minipig reflects the human timeframes better; however the lack of prenatal maternal-fetal immune interaction in minipig may cause less responsiveness to prenatal intervention. It is too early to conclude which immune parameters are most appropriate, because there are not enough comparative immune parameters. Filling these gaps will increase the predictability of results observed in experimental animals, and guide future intervention studies by assessing relevant parameters in the right corresponding developmental time frames. PMID- 27282948 TI - Serotonin reuptake inhibitors and heart defects. PMID- 27282946 TI - E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation. AB - miR-17 family microRNAs (miRNAs) are crucial for embryo development, however, their role in muscle development is still unclear. miR-20a-5p and miR-20b-5p belong to the miR-17 family and are transcribed from the miR-17~92 and miR 106a~363 clusters respectively. In this study, we found that miR-20a-5p and miR 20b-5p promoted myoblast differentiation and repressed myoblast proliferation by directly binding the 3' UTR of E2F transcription factor 1 (E2F1) mRNA. E2F1 is an important transcriptional factor for organism's normal development. Overexpression of E2F1 in myoblasts promoted myoblast proliferation and inhibited myoblast differentiation. Conversely, E2F1 inhibition induced myoblast differentiation and repressed myoblast proliferation. Moreover, E2F1 can bind directly to promoters of the miR-17~92 and miR-106a~363 clusters and activate their transcription, and E2F1 protein expression is correlated with the expression of pri-miR-17~92 and pri-miR-106a~363 during myoblast differentiation. These results suggested an auto-regulatory feedback loop between E2F1 and miR-20a 5p/20b-5p, and indicated that miR-20a-5p, miR-20b-5p and E2F1 are involved in myoblast proliferation and differentiation through the auto-regulation between E2F1 and miR-20a-5p/20b-5p. These findings provide new insight into the mechanism of muscle differentiation, and further shed light on the understanding of muscle development and muscle diseases. PMID- 27282950 TI - The histopathological structures of the extrapleural hematoma wall: A case report. AB - Extrapleural hematoma is a rare condition in which blood is present in the extrapleural space, which sometimes causes death due to respiratory failure. Although a single low-density stripe, called a "displaced extrapleural fat sign," can be detected in chest computed tomographic (CT) scans, no reports have confirmed this structure histopathologically. We performed an autopsy on a patient with extrapleural hematoma who died of respiratory failure. An extrapleural fat sign was detected on the antemortem CT. We investigated the wall structure histopathologically. The hematoma wall was composed of parietal pleura, a sub-pleural layer, an extrapleural fat layer and endothoracic fascia. The case indicated that extrapleural hematoma occurs at the endothoracic fascia. PMID- 27282949 TI - Effects of nano-TiO2 -LDPE packaging on postharvest quality and antioxidant capacity of strawberry (Fragaria ananassa Duch.) stored at refrigeration temperature. AB - BACKGROUND: Nano-TiO2 -low-density polyethylene (NTLDPE) packaging was prepared, and the effects of NTLDPE packaging on quality and antioxidant capacity of strawberry fruits were investigated. RESULTS: With increased barrier properties, NTLDPE packaging quickly formed a relative lower O2 and higher CO2 air composition in comparison with LDPE. It was also more efficient in maintaining the overall quality of strawberry fruit, as reflected by lower decay rate and weight loss, as well as retarding the decrease in firmness and titratable acid. Meanwhile, reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide in NTLDPE-packed fruits were 10.8% and 21.9% lower, respectively. Furthermore, the activities of antioxidant enzymes involved in ROS scavenging in NTLDPE-packed fruits were significantly higher at the later period of storage time. Anthocyanin accumulation was inhibited, whereas ascorbic acid and total phenolics contents were better retained and 1-diphenyl-2-picrylhydrazyl radical scavenging activity was 13.2% higher in NTLDPE-packed fruit by the end of storage. CONCLUSION: These data indicate that the beneficial effects of NTLDPE packaging on postharvest quality and antioxidant capacity of strawberry are probably associated with the promotion of ROS scavenging and related antioxidant enzyme activities, and NTLDPE packaging together with refrigeration storage is a promising method for strawberry fruit preservation. (c) 2016 Society of Chemical Industry. PMID- 27282951 TI - Recreational inhalation of butane and propane in adolescents: Two forensic cases of accidental death. AB - The recreational use of inhalants is a fairly widespread habit among adolescents because of the ease of availability and methods of assumption. Their use is however not free of risks, both for direct toxicity on several target organs and for a mechanism of gas replacement with lack of oxygen. The first case concerns a 12-year-old boy who died suddenly after sniffing a mix of butane and propane contained in a can of air freshener. The second case concerns a 14-year-old boy who died by acute poisoning by the same mixture contained in a refill for lighters. High concentrations of the compounds were found in the tissues by analysis with gas chromatography-mass spectrometry. The compounds found in tissues and biological fluids were perfectly compatible with those contained in the containers used for the inhalation. The mechanisms of death were therefore assessed in a combination of the direct toxicity of the compound and oxygen replacement, thus highlighting the crucial help that toxicological analyses can provide in such cases. PMID- 27282952 TI - Testosterone Administration Moderates Effect of Social Environment on Trust in Women Depending on Second-to-Fourth Digit Ratio. AB - Animal research has established that effects of hormones on social behaviour depend on characteristics of both individual and environment. Insight from research on humans into this interdependence is limited, though. Specifically, hardly any prior testosterone experiments in humans scrutinized the interdependency of testosterone with the social environment. Nonetheless, recent testosterone administration studies in humans repeatedly show that a proxy for individuals' prenatal testosterone-to-estradiol ratio, second-to-fourth digit ratio (2D:4D ratio), influences effects of testosterone administration on human social behaviour. Here, we systematically vary the characteristics of the social environment and show that, depending on prenatal sex hormone priming, testosterone administration in women moderates the effect of the social environment on trust. We use the economic trust game and compare one-shot games modelling trust problems in relations between strangers with repeated games modelling trust problems in ongoing relations between partners. As expected, subjects are more trustful in repeated than in one-shot games. In subjects prenatally relatively highly primed by testosterone, however, this effect disappears after testosterone administration. We argue that impairments in cognitive empathy may reduce the repeated game effect on trust after testosterone administration in subjects with relatively high prenatal testosterone exposure and propose a neurobiological explanation for this effect. PMID- 27282953 TI - Internal guide RNA interactions interfere with Cas9-mediated cleavage. AB - The CRISPR/Cas system uses guide RNAs (gRNAs) to direct sequence-specific DNA cleavage. Not every gRNA elicits cleavage and the mechanisms that govern gRNA activity have not been resolved. Low activity could result from either failure to form a functional Cas9-gRNA complex or inability to recognize targets in vivo. Here we show that both phenomena influence Cas9 activity by comparing mutagenesis rates in zebrafish embryos with in vitro cleavage assays. In vivo, our results suggest that genomic factors such as CTCF inhibit mutagenesis. Comparing near identical gRNA sequences with different in vitro activities reveals that internal gRNA interactions reduce cleavage. Even though gRNAs containing these structures do not yield cleavage-competent complexes, they can compete with active gRNAs for binding to Cas9. These results reveal that both genomic context and internal gRNA interactions can interfere with Cas9-mediated cleavage and illuminate previously uncharacterized features of Cas9-gRNA complex formation. PMID- 27282954 TI - Handheld reflectance confocal microscopy for the diagnosis of molluscum contagiosum: Histopathology and dermoscopy correlation. AB - Handheld reflectance confocal microscopy may represent an adjunctive, fast, non invasive tool for the diagnosis of molluscum contagiosum, revealing microscopic details closely related to histopathology, as demonstrated by this study evaluating 19 molluscum lesions in 11 patients. It permits the rapid examination of one or multiple skin lesions in real time and it is perfectly suitable for children. PMID- 27282956 TI - MicroRNAs in oral lichen planus and potential miRNA-mRNA pathogenesis with essential cytokines: a review. AB - Oral lichen planus (OLP) is a potentially premalignant condition with unknown pathogenesis. Immune and inflammatory factors are thought to play important roles in the development of OLP, and cytokines, such as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, can act as critical players in the immunopathogenesis of OLP. MicroRNAs (miRNAs) are closely correlated with cytokines in various inflammation-related diseases. In patients with OLP, miRNA 146a and miRNA-155 are increased in peripheral blood mononuclear cells, and numerous miRNAs have been shown to exhibit altered expression profiles in lesions. Although the microRNA-messenger RNA (miRNA-mRNA) network is thought to be involved in the development of OLP, in-depth studies are lacking. Here, we summarize current data on the mechanisms of action of miRNAs regulating typical cytokines in OLP, including interleukin (IL)-10, IL-17, IL-22, IFN-gamma, and TNF alpha, to study the genetic basis of the pathogenesis of OLP and to provide prospects of therapy. PMID- 27282955 TI - A faulty interaction between SOD1 and hCCS in neurodegenerative disease. AB - A proportion of Amyotrophic lateral sclerosis (ALS) cases result from impaired mutant superoxide dismutase-1 (SOD1) maturation. The copper chaperone for SOD1 (hCCS) forms a transient complex with SOD1 and catalyses the final stages of its maturation. We find that a neurodegenerative disease-associated hCCS mutation abrogates the interaction with SOD1 by inhibiting hCCS zinc binding. Analogously, SOD1 zinc loss has a detrimental effect on the formation, structure and disassociation of the hCCS-SOD1 heterodimer. This suggests that hCCS functionality is impaired by ALS mutations that reduce SOD1 zinc affinity. Furthermore, stabilization of wild-type SOD1 by chemical modification including cisplatination, inhibits complex formation. We hypothesize that drug molecules designed to stabilize ALS SOD1 mutants that also target the wild-type form will lead to characteristics common in SOD1 knock-outs. Our work demonstrates the applicability of chromatographic SAXS when studying biomolecules predisposed to aggregation or dissociation; attributes frequently reported for complexes involved in neurodegenerative disease. PMID- 27282957 TI - Successful Treatment of Keratosis Pilaris Rubra with Pulsed Dye Laser. AB - BACKGROUND: Keratosis pilaris rubra is a common but rarely reported condition characterized by follicular-based hyperkeratotic papules on a background of erythema. It can be embarrassing and symptomatic for patients, particularly adolescent boys. We sought to explore the efficacy of pulsed dye laser (PDL) in the treatment of keratosis pilaris rubra. METHODS: Eight patients were treated with PDL for keratosis pilaris rubra. RESULTS: All patients reported noticeable improvement after one to four treatments. CONCLUSIONS: PDL is an effective, easily accessible, and underused therapy in the treatment of keratosis pilaris rubra. PMID- 27282958 TI - Droplet Enhanced Fluorescence for Ultrasensitive Detection Using Inkjet. AB - A fluorescence enhanced phenomenon was found within a micrometer-sized liquid droplet, and it was adopted to construct droplet enhanced fluorescence (DEF) for ultrasensitive fluorescence detection. In this paper, an inkjet was utilized to eject perfect spherical droplets to construct a microspherical resonator and to develop a DEF system. It was utilized to implement ultrasensitive fluorescence detection in a liquid specimen with a volume of several microliters. The DEF detection of fluorescent molecules, fluorescein sodium, was used as a model to validate the proposed enhanced fluorescence detection method. A low limit of detection (LOD) for fluorescein sodium of 124 pM was obtained. The sensitive detection of single stranded DNA (ssDNA) was experimentally completed, with a wide range of linearity with a LOD of 312 pM. The proposed mechanism can be used as an ultrasensitive detection technique for analyzing microliters of liquid samples. PMID- 27282959 TI - The modulation of Schottky barriers of metal-MoS2 contacts via BN-MoS2 heterostructures. AB - Using first-principles calculations within density functional theory, we systematically studied the effect of BN-MoS2 heterostructure on the Schottky barriers of metal-MoS2 contacts. Two types of FETs are designed according to the area of the BN-MoS2 heterostructure. Results show that the vertical and lateral Schottky barriers in all the studied contacts, irrespective of the work function of the metal, are significantly reduced or even vanish when the BN-MoS2 heterostructure substitutes the monolayer MoS2. Only the n-type lateral Schottky barrier of Au/BN-MoS2 contact relates to the area of the BN-MoS2 heterostructure. Notably, the Pt-MoS2 contact with n-type character is transformed into a p-type contact upon substituting the monolayer MoS2 by a BN-MoS2 heterostructure. These changes of the contact natures are ascribed to the variation of Fermi level pinning, work function and charge distribution. Analysis demonstrates that the Fermi level pinning effects are significantly weakened for metal/BN-MoS2 contacts because no gap states dominated by MoS2 are formed, in contrast to those of metal MoS2 contacts. Although additional BN layers reduce the interlayer interaction and the work function of the metal, the Schottky barriers of metal/BN-MoS2 contacts still do not obey the Schottky-Mott rule. Moreover, different from metal MoS2 contacts, the charges transfer from electrodes to the monolayer MoS2, resulting in an increment of the work function of these metals in metal/BN-MoS2 contacts. These findings may prove to be instrumental in the future design of new MoS2-based FETs with ohmic contact or p-type character. PMID- 27282960 TI - Body weight support impacts lateral stability during treadmill walking. AB - Body weight support (BWS) systems are a common tool used in gait rehabilitation. BWS systems may alter the requirements for an individual to actively stabilize by 1) providing lateral restoring forces that reduce the requirements for the nervous system to actively stabilize and 2) decreasing the stabilizing gravitational moment in the frontal plane, which could increase the requirements to actively stabilize. The goal of the current study was to quantify the interaction between BWS and lateral stability. We hypothesized that when able bodied people walk with BWS: 1) the lateral restoring forces provided by BWS would reduce the requirements to stabilize in the frontal plane when comparing dynamically similar gaits, and 2) increasing BWS would decrease the stabilizing gravitational moment in the frontal plane and increase the requirements to stabilize when speed is constrained. Our findings partly support these hypotheses, but indicate a complex interaction between BWS and lateral stability. With BWS, subjects significantly decreased step width variability and significantly increased step width (p<0.05) for both the dynamically similar and Speed-Matched conditions. The decrease in step width variability may be attributable to a combination of lateral restoring forces decreasing the mechanical requirements to stabilize and an enhanced sense of position that could have improved locomotor control. Increases in step width when walking with high levels of BWS could have been due to decreases in the gravitational moment about the stance limb, which may challenge the control of stability in multiple planes. PMID- 27282962 TI - Corrigendum. PMID- 27282961 TI - Physiological vortices in the sinuses of Valsalva: An in vitro approach for bio prosthetic valves. AB - PURPOSE: The physiological flow dynamics within the Valsalva sinuses, in terms of global and local parameters, are still not fully understood. This study attempts to identify the physiological conditions as closely as possible, and to give an explanation of the different and sometime contradictory results in literature. METHODS: An in vitro approach was implemented for testing porcine bio-prosthetic valves operating within different aortic root configurations. All tests were performed on a pulse duplicator, under physiological pressure and flow conditions. The fluid dynamics established in the various cases were analysed by means of 2D Particle Image Velocimetry, and related with the achieved hydrodynamic performance. RESULTS: Each configuration is associated with substantially different flow dynamics, which significantly affects the valve performance. The configuration most closely replicating healthy native anatomy was characterised by the best hemodynamic performance, and any mismatch in size and position between the valve and the root produced substantial modification of the fluid dynamics downstream of the valve, hindering the hydrodynamic performance of the system. The worst conditions were observed for a configuration characterised by the total absence of the Valsalva sinuses. CONCLUSION: This study provides an explanation for the different vortical structures described in the literature downstream of bioprosthetic valves, enlightening the experimental complications in valve testing. Most importantly, the results clearly identify the fluid mechanisms promoted by the Valsalva sinuses to enhance the ejection and closing phases, and this study exposes the importance of an optimal integration of the valve and root, to operate as a single system. PMID- 27282963 TI - The first single responders in Sweden - Evaluation of a pre-hospital single staffed unit. AB - BACKGROUND: Single responder (SR) systems have been implemented in several countries. When the very first SR system in Sweden was planned, it was criticised because of concerns about sending single emergency nurses out on alerts. In the present study, the first Swedish SR unit was studied in order to register waiting times and assess the working environment. METHOD: Quantitative data were collected from the ambulance dispatch register. Data on the working environment were collected using a questionnaire sent to the SR staff. RESULTS: The SR system reduced the average patient waiting time from 26 to 13min. It also reduced the number of ambulance transports by 35% following triage of patient(s) priority determined by the SR. The staff perceived the working environment to be adequate. CONCLUSION: The SR unit was successful in that it reduced waiting times to prehospital health care. Contrary to expectations, it proved to be an adequate working environment. There is good reason to believe that SR systems will spread throughout the country. In order to enhance in depth the statistical analysis, additional should be collected over a longer time period and from more than one SR unit. PMID- 27282964 TI - Preclinical evaluation of olaparib and metformin combination in BRCA1 wildtype ovarian cancer. AB - OBJECTIVES: BRCA mutated ovarian cancers show increased responsiveness to PARP inhibitors. PARP inhibitors target DNA repair and provide a second hit to BRCA mutated tumors, resulting in "synthetic lethality". We investigated a combination of metformin and olaparib to provide "synthetic lethality" in BRCA intact ovarian cancer cells. METHODS: Ovarian cancer cell lines (UWB1.289, UWB1.289.BRCA, SKOV3, OVCAR5, A2780 and C200) were treated with a combination of metformin and olaparib. Cell viability was assessed by MTT and colony formation assays. Flow cytometry was used to detect cell cycle events. In vivo studies were performed in SKOV3 or A2780 xenografts in nude mice. Animals were treated with single agent, metformin or olaparib or combination. Molecular downstream effects were examined by immunohistochemistry. RESULTS: Compared to single drug treatment, combination of olaparib and metformin resulted in significant reduction of cell proliferation and colony formation (p<0.001) in ovarian cancer cells. This treatment was associated with a significant S-phase cell cycle arrest (p<0.05). Combination of olaparib and metformin significantly inhibited SKOV3 and A2780 ovarian tumor xenografts which were accompanied with decreased Ki-index (p<0.001). Metformin did not affect DNA damage signaling, while olaparib induced adenosine monophosphate activated kinase activation; that was further potentiated with metformin combination in vivo. CONCLUSION: Combining PARP inhibitors with metformin enhances its anti-proliferative activity in BRCA mutant ovarian cancer cells. Furthermore, the combination showed significant activity in BRCA intact cancer cells in vitro and in vivo. This is a promising treatment regimen for women with epithelial ovarian cancer irrespective of BRCA status. PMID- 27282965 TI - Prognostic Utility of Immunoprofiling in Colon Cancer: Results from a Prospective, Multicenter Nodal Ultrastaging Trial. AB - BACKGROUND: Retrospective data indicate that immunoprofiling of T cell markers can be prognostic in colon cancer. Prospective T cell immunoprofiling of colon cancer has not been well defined for patients whose lymph nodes are ultrastaged. STUDY DESIGN: A prospective cohort was selected from patients enrolled in an ongoing phase II multicenter trial of nodal ultrastaging for colon cancer. Primary tumor specimens from 89 patients were analyzed by immunohistochemistry for the T cells CD3(+), CD4(+), CD8(+), and FOXP3(+). Lymphocyte populations were quantified with digital image analysis. Results were examined for their association with 5-year disease-free survival along with TNM stage and clinicopathologic variables. RESULTS: Longer disease-free survival was associated with higher CD3(+) counts at the invasive margin (IM) (p = 0.005), higher CD8(+) counts at the tumor center (TC) and IM (p = 0.002), a lower CD4(+)/CD8(+) ratio at the TC+IM (p = 0.027), and a higher CD8(+)/FOXP3(+) ratio at the TC+IM (p = 0.020). After multivariable analysis, CD8(+) at the TC+IM (p = 0.002), the CD8(+)/FOXP3(+) ratio at the TC+IM (p = 0.004), and the number of tumor-positive lymph nodes (p = 0.003) remained significant. CONCLUSIONS: This is the first prospective demonstration of the prognostic utility of immunoprofiling in colon cancer after nodal ultrastaging. Staging based on tumor immunoprofile can augment TNM staging and provide targets for specific immunotherapies. PMID- 27282967 TI - Ebselen alters cellular oxidative status and induces endoplasmic reticulum stress in rat hippocampal astrocytes. AB - Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. Because of its properties, it may be protective against injury to the nervous tissue. However, evidence suggests that its glutathione peroxidase activity could underlie certain deleterious actions on cell physiology. In this study we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular oxidative status, cytosolic free-Ca(2+) concentration ([Ca(2+)]c), setting of endoplasmic reticulum stress and phosphorylation of glial fibrillary acidic protein and major mitogen-activated protein kinases were analyzed. Our results show that ebselen induced a concentration-dependent increase in the generation of reactive oxygen species in the mitochondria. We observed a concentration dependent increase in global cysteine oxidation and in the level of malondialdehyde in the presence of ebselen. We also detected increases in catalase, glutathione S-transferase and glutathione reductase activity. Ebselen also evoked a concentration-dependent increase in [Ca(2+)]c. Moreover, we observed a concentration-dependent increase in the phosphorylation of the unfolded protein response markers, eukaryotic translation initiation factor 2alpha and X-box binding protein 1. Finally, ebselen also induced an increase in the phosphorylation of glial fibrillary acidic protein, SAPK/JNK, p38 MAPK and p44/42 MAPK. Our results provide strong evidence that implicate endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in an oxidative damage of cells in the presence of ebselen. The compound thus might exert deleterious actions on astrocyte physiology that could compromise their function. PMID- 27282968 TI - Estimation of L-threonine requirements for Longyan laying ducks. AB - OBJECTIVE: A study was conducted to test six threonine (Thr) levels (0.39%, 0.44%, 0.49%, 0.54%, 0.59%, and 0.64%) to estimate the optimal dietary Thr requirements for Longyan laying ducks from 17 to 45 wk of age. METHODS: Nine hundred Longyan ducks aged 17 wk were assigned randomly to the six dietary treatments, where each treatment comprised six replicate pens with 25 ducks per pen. RESULTS: Increasing the Thr level enhanced egg production, egg weight, egg mass, and the feed conversion ratio (FCR) (linearly or quadratically; p<0.05). The Haugh unit score, yolk color, albumen height, and the weight, percentage, thickness, and breaking strength of the eggshell did not response to increases in the Thr levels, but the albumen weight and its proportion increased significantly (p<0.05), whereas the yolk weight and its proportion decreased significantly as the Thr levels increased. CONCLUSION: According to a regression model, the optimal Thr requirement for egg production, egg mass, and FCR in Longyan ducks is 0.57%, while 0.58% is the optimal level for egg weight from 17 to 45 wk of age. PMID- 27282966 TI - Translating microfluidics: Cell separation technologies and their barriers to commercialization. AB - Advances in microfluidic cell sorting have revolutionized the ways in which cell containing fluids are processed, now providing performances comparable to, or exceeding, traditional systems, but in a vastly miniaturized format. These technologies exploit a wide variety of physical phenomena to manipulate cells and fluid flow, such as magnetic traps, sound waves and flow-altering micropatterns, and they can evaluate single cells by immobilizing them onto surfaces for chemotherapeutic assessment, encapsulate cells into picoliter droplets for toxicity screenings and examine the interactions between pairs of cells in response to new, experimental drugs. However, despite the massive surge of innovation in these high-performance lab-on-a-chip devices, few have undergone successful commercialization, and no device has been translated to a widely distributed clinical commodity to date. Persistent challenges such as an increasingly saturated patent landscape as well as complex user interfaces are among several factors that may contribute to their slowed progress. In this article, we identify several of the leading microfluidic technologies for sorting cells that are poised for clinical translation; we examine the principal barriers preventing their routine clinical use; finally, we provide a prospectus to elucidate the key criteria that must be met to overcome those barriers. Once established, these tools may soon transform how clinical labs study various ailments and diseases by separating cells for downstream sequencing and enabling other forms of advanced cellular or sub-cellular analysis. (c) 2016 International Clinical Cytometry Society. PMID- 27282969 TI - Effects of dietary marigold extract supplementation on growth performance, pigmentation, antioxidant capacity and meat quality in broiler chickens. AB - OBJECTIVE: This experiment was conducted to investigate the effects of dietary supplementation with marigold extract on growth performance, pigmentation, antioxidant capacity and meat quality in broiler chickens. METHODS: A total of 320 one-day-old Arbor Acres chickens were randomly divided into 5 groups with 8 replicates of 8 chickens each. The chickens of control group were fed with basal diet and other experimental groups were fed with basal diet supplemented with 0.075%, 0.15%, 0.30%, and 0.60% marigold extract respectively (the corresponding concentrations of lutein were 15, 30, 60, and 120 mg/kg). RESULTS: The results showed that marigold extract supplementation increased the yellowness values of shank, beak, skin and muscle and the redness (a*) value of thigh muscle (linear, p<0.01). Marigold extract supplementation significantly increased the total antioxidant capacity, and the activities of superoxide dismutase in liver and thigh muscle (linear, p<0.01) and significantly decreased the malondialdehyde contents of liver and thigh muscle (linear, p<0.01). Marigold extract supplementation significantly decreased the drip loss and shear force of thigh muscles (linear, p<0.01). There was no significant effect on growth performance with marigold extract supplementation. CONCLUSION: In conclusion, dietary supplementation of marigold extract significantly increased the yellowness values of carcass, antioxidant capacity and meat quality in broiler chickens. PMID- 27282970 TI - Effects of Octacosanol Extracted from Rice Bran on the Laying Performance, Egg Quality and Blood Metabolites of Laying Hens. AB - A 42-d study with 384 Hy-line brown laying hens was conducted to assess the effects of dietary octacosanol supplementation on laying performance, egg quality and blood metabolites of laying hens. Hens were randomly allocated into 4 dietary groups of 8 cages each, which were fed basal diet supplemented with 0 (Control), 9 (OCT9), 18 (OCT18), and 27 (OCT27) mg/kg diet of octacosanol isolated from rice bran, respectively. The experiment was conducted in an environmental controlled house and hens were fed twice daily for ad libitum intake. Laying performance was determined over the 42-d period, and egg quality as well as blood metabolites were estimated on d 21 and d 42. Diets in OCT18 and OCT27 increased (p<0.05) laying rate, egg weight, egg mass, egg albumen height, Haugh unit and eggshell strength on d 42, but decreased (p<0.05) feed conversion rate and levels of total cholesterol, triglyceride and low density lipoprotein cholesterol in the serum as compared to those of Control. Feed intake, yolk color, yolk diameter, eggshell thickness and high density lipoprotein cholesterol were similar (p>0.05) among treatments. Results demonstrate that supplementing 18 to 27 mg/kg diet of rice bran octacosanol can improve laying rate and egg quality and reduce blood lipid of laying hens. PMID- 27282971 TI - Black gram (Vigna Mungo L.) foliage supplementation to crossbred cows: effects on feed intake, nutrient digestibility and milk production. AB - OBJECTIVE: An experiment was conducted to examine the effect of dietary supplementation of dried and ground foliage of black gram (Vigna mungo L.) on feed intake and utilization, and production performance of crossbred lactating cows. METHODS: Eighteen lactating crossbred (Bos taurus*Bos indicus) cows (body weight 330.93+/- 10.82 kg) at their second and mid lactation (milk yield 6.77+/ 0.54 kg/d) were randomly divided into three groups of six each in a completely randomized block design. Three supplements were formulated by quantitatively replacing 0, 50, and 100 per cent of dietary wheat bran of concentrate mixture with dried and ground foliage of black gram. The designated supplement was fed to each group with basal diet of rice straw (ad libitum) to meet the requirements for maintenance and milk production. Daily feed intake and milk yield was recorded. A digestion trial was conducted to determine the total tract digestibility of various nutrients. RESULTS: The daily feed intake was increased (p<0.05) with the supplementation of black gram foliage. Although the digestibility of dry matter, organic matter, crude protein, and ether extract did not vary (p>0.05), the fibre digestibility was increased (p<0.05), which ultimately improved (p<0.05) the total digestible nutrients content of composite diet. Although, the average milk yield (kg/animal/d) and composition did not differ (p>0.05) among the groups, milk yield was increased by 10 per cent with total replacement of wheat bran in concentrate mixture with of black gram foliage. The economics of milk production calculated as feed cost per kg milk yield (INR 10.61 vs 7.98) was reduced by complete replacement of wheat bran with black gram foliage. CONCLUSION: Black gram foliage could be used as complete replacement for wheat bran in concentrate mixture of dairy cows in formulating least cost ration for economic milk production in small holders' animal production. PMID- 27282972 TI - Heat tolerance in Brazilian hair sheep. AB - OBJECTIVE: The aim of this study was to evaluate heat tolerance using heat tolerance indices, physiological, physical, thermographic, and hematological parameters in Santa Ines and Morada Nova sheep breeds in the Federal District, Brazil. METHODS: Twenty-six adult hair sheep, one and a half years old, from two genetic groups (Santa Ines: 12 males and 4 females; Morada Nova: 7 males and 3 females) were used and data (rectal temperature, respiratory rate, heart rate, skin temperatures; hematological parameters) were collected during three consecutive days, twice a day (morning and afternoon), with a total of six repetitions. Also physical parameters (biometric measurements, skin and hair traits) and heat tolerance indices (temperature-humidity index, Iberia and Benezra) were evaluated. The analyses included analyses of variance, correlation, and principal components with a significance level of 5%. RESULTS: The environmental indices, in general, indicate a situation of thermal discomfort for the animals during the afternoon. Breed significantly influenced (p<0.001) physiological and physical characteristics of skin, hair, biometric measurements and Iberia and Benezra heat tolerance indices. Santa Ines animals were bigger and had longer, greater number and darker hair, thicker skin, greater respiratory rate and Benezra index and lower Iberia index compared with Morada Nova breed. CONCLUSION: Although both breeds can be considered adapted to the environmental conditions of the region, Morada Nova breed is most suitable for farming in the Midwest region. The positive correlation found between the thermographic temperatures and physiological parameters indicates that this technique can be used to evaluate thermal comfort. Also, it has the advantage that animals do not have to be handled, which favors animal welfare. PMID- 27282973 TI - Genetic correlations between first parity and accumulated second to last parity reproduction traits as selection aids to improve sow lifetime productivity. AB - OBJECTIVE: The objective of this research was to estimate genetic correlations between number of piglets born alive in the first parity (NBA1), litter birth weight in the first parity (LTBW1), number of piglets weaned in the first parity (NPW1), litter weaning weight in the first parity (LTWW1), number of piglets born alive from second to last parity (NBA2+), litter birth weight from second to last parity (LTBW2+), number of piglets weaned from second to last parity (NPW2+) and litter weaning weight from second to last parity (LTWW2+), and to identify the percentages of animals (the top 10%, 25%, and 50%) for first parity and sums of second and later parity traits. METHODS: The 9,830 records consisted of 2,124 Landrace (L), 724 Yorkshire (Y), 2,650 LY, and 4,332 YL that had their first farrowing between July 1989 and December 2013. The 8-trait animal model included the fixed effects of first farrowing year-season, additive genetic group, heterosis of the sow and the litter, age at first farrowing, and days to weaning (NPW1, LTWW1, NPW2+, and LTWW2+). Random effects were animal and residual. RESULTS: Heritability estimates ranged from 0.08+/-0.02 (NBA1 and NPW1) to 0.29+/ 0.02 (NPW2+). Genetic correlations between reproduction traits in the first parity and from second to last parity ranged from 0.17+/-0.08 (LTBW1 and LTBW2+) to 0.67+/-0.06 (LTWW1 and LTWW2+). Phenotypic correlations between reproduction traits in the first parity and from second to last parity were close to zero. Rank correlations between LTWW1 and LTWW2+ estimated breeding value tended to be higher than for other pairs of traits across all replacement percentages. CONCLUSION: These rank correlations indicated that selecting boars and sows using genetic predictions for first parity reproduction traits would help improve reproduction traits in the second and later parities as well as lifetime productivity in this swine population. PMID- 27282974 TI - Supplementation of Dried Mealworm (Tenebrio molitor larva) on Growth Performance, Nutrient Digestibility and Blood Profiles in Weaning Pigs. AB - This experiment was conducted to investigate the effects of dried mealworm (Tenebrio molitor larva) on growth performance, nutrient digestibility and blood profiles in weaning pigs. A total of 120 weaning pigs (28+/-3 days and 8.04+/ 0.08 kg of body weight) were allotted to one of five treatments, based on sex and body weight, in 6 replicates with 4 pigs per pen by a randomized complete block design. Supplementation level of dried mealworm was 0%, 1.5%, 3.0%, 4.5%, or 6.0% in experimental diet as treatment. Two phase feeding programs (phase I from 0 day to 14 day, phase II from 14 day to 35 day) were used in this experiment. All animals were allowed to access diet and water ad libitum. During phase I, increasing level of dried mealworm in diet linearly improved the body weight (p<0.01), average daily gain (ADG) (p<0.01) and average daily feed intake (ADFI) (p<0.01). During phase II, ADG also tended to increase linearly when pigs were fed higher level of dried mealworm (p = 0.08). In addition, increasing level of dried mealworm improved the ADG (p<0.01), ADFI (p<0.05) and tended to increase gain to feed ratio (p = 0.07) during the whole experimental period. As dried mealworm level was increased, nitrogen retention and digestibility of dry matter as well as crude protein were linearly increased (p = 0.05). In the results of blood profiles, decrease of blood urea nitrogen (linear, p = 0.05) and increase of insulin-like growth factor (linear, p = 0.03) were observed as dried mealworm was increased in diet during phase II. However, there were no significant differences in immunoglobulin A (IgA) and IgG concentration by addition of dried mealworm in the growth trial. Consequently, supplementation of dried mealworm up to 6% in weaning pigs' diet improves growth performance and nutrient digestibility without any detrimental effect on immune responses. PMID- 27282975 TI - Effects of Dietary Energy Levels on the Physiological Parameters and Reproductive Performance of Gestating Gilts. AB - This experiment was conducted to investigate the effects of dietary energy levels on the physiological parameters and reproductive performance of gestating first parity sows. A total of 52 F1 gilts (Yorkshire*Landrace) were allocated to 4 dietary treatments using a completely randomized design. Each treatment contained diets with 3,100, 3,200, 3,300, or 3,400 kcal of metabolizable energy (ME)/kg, and the daily energy intake of the gestating gilts in each treatment were 6,200, 6,400, 6,600, and 6,800 kcal of ME, respectively. During gestation, the body weight (p = 0.04) and weight gain (p = 0.01) of gilts linearly increased with increasing dietary energy levels. Backfat thickness was not affected at d110 of gestation by dietary treatments, but increased linearly (p = 0.05) from breeding to d 110 of gestation. There were no significant differences on the litter size or litter birth weight. During lactation, the voluntary feed intake of sows tended to decrease when the dietary energy levels increased (p = 0.08). No difference was observed in backfat thickness of the sows within treatments; increasing energy levels linearly decreased the body weight of sows (p<0.05) at d 21 of lactation and body weight gain during lactation (p<0.01). No significant differences were observed in the chemical compositions of colostrum and milk. Therefore, these results indicated that high-energy diets influenced the bodyweight and backfat thickness of sows during gestation and lactation. NRC (2012) suggested that the energy requirement of the gestation gilt should be between 6,678 and 7,932 kcal of ME/d. Similarly, our results suggested that 3,100 kcal of ME/kg is not enough to maintain the reproductive performance for gilts during gestation with 2 kg feed daily. Gilts in the treatment 3,400 kcal of ME/kg have a higher weaning number of piglets, but bodyweight and backfat loss were higher than other treatments during lactation. But bodyweight and backfat loss were higher than other treatments during lactation. Consequently, an adequate energy requirement of gestating gilts is 6,400 kcal of ME/d. PMID- 27282976 TI - Is CH3NH3PbI3 Polar? AB - In view of the continued controversy concerning the polar/nonpolar nature of the hybrid perovskite system, CH3NH3PbI3, we report the first investigation of a time resolved pump-probe measurement of the second harmonic generation efficiency as well as using its more traditional form as a sensitive probe of the absence/presence of the center of inversion in the system both in its excited and ground states, respectively. Our results clearly show that SHG efficiency, if nonzero, is below the limit of detection, strongly indicative of a nonpolar or centrosymmetric structure. Our results on the same samples, based on temperature dependent single crystal X-ray diffraction and P-E loop measurements, are entirely consistent with the above conclusion of a centrosymmetric structure for this compound in all three phases, namely the high temperature cubic phase, the intermediate temperature tetragonal phase and the low temperature orthorhombic phase. It is important to note that all our experimental probes are volume averaging and performed on bulk materials, suggesting that basic material properties of CH3NH3PbI3 are consistent with a centrosymmetric, nonpolar structure. PMID- 27282977 TI - Nurse Practitioners' Comfort in Treating Work-Related Injuries in Adolescents. AB - This study examined nurse practitioners' (NPs) previous experiences and comfort levels in treating adolescents with work-related injuries in two states where NPs have statutory authority to treat work-related injuries. The authors surveyed all actively licensed NPs in Washington and Oregon (N = 4,849). Factors associated with NPs' previous experiences and comfort in treating adolescents with work related injuries were identified using modified Poisson regression. Less than a quarter of respondents (21.1%, n = 225) reported having ever treated an adolescent for a work-related injury. Nearly half (43.6%) of respondents reported being uncomfortable or very uncomfortable in treating adolescents with work related injuries. Previous experience and male gender were associated with greater likelihood of feeling comfortable (p < .01). Nurse practitioners serve as primary care providers for adolescents who may experience work-related injuries. This study documents the need for developing educational and outreach efforts to better prepare NPs to treat adolescents' work-related injuries. PMID- 27282978 TI - The Importance of Employee Breaks. AB - The occupational and environmental health nurse should encourage workers to take work breaks. Breaks enable all workers to perform at their best. PMID- 27282979 TI - Burnout and Engagement: Relative Importance of Predictors and Outcomes in Two Health Care Worker Samples. AB - This study's purpose was twofold: first, to examine the relative importance of job demands and resources as predictors of burnout and engagement, and second, the relative importance of engagement and burnout related to health, depressive symptoms, work ability, organizational commitment, and turnover intentions in two samples of health care workers. Nurse leaders ( n = 162) and licensed emergency medical technicians (EMTs; n = 102) completed surveys. In both samples, job demands predicted burnout more strongly than job resources, and job resources predicted engagement more strongly than job demands. Engagement held more weight than burnout for predicting commitment, and burnout held more weight for predicting health outcomes, depressive symptoms, and work ability. Results have implications for the design, evaluation, and effectiveness of workplace interventions to reduce burnout and improve engagement among health care workers. Actionable recommendations for increasing engagement and decreasing burnout in health care organizations are provided. PMID- 27282980 TI - NF-kappaB in acute pancreatitis: Mechanisms and therapeutic potential. AB - The incidence of acute pancreatitis (AP) is increasing globally and mortality could be high among patients with organ failure and infected necrosis. The predominant factors responsible for the morbidity and mortality of AP are systemic inflammatory response syndrome and multiorgan dysfunction. Even though preclinical studies have shown antisecretory agents (somatostatin), antioxidants (S-adenosyl methionine [SAM], selenium), protease inhibitors, platelet activating factor inhibitor (Lexipafant), and anti-inflammatory immunomodulators (eg. prostaglandin E, indomethacin) to benefit AP in terms of reducing the severity and/or mortality, most of these agents have shown heterogeneous results in clinical studies. Several years of experimental studies have implicated nuclear factor-kappa B (NF-kappaB) activation as an early and central event in the progression of inflammation in AP. In this manuscript, we review the literature on the role of NF-kappaB in the pathogenesis of AP, its early intraacinar activation, and how it results in progression of the disease. We also discuss why anti-protease, antisecretory, and anti-inflammatory agents are unlikely to be effective in clinical acute pancreatitis. NF-kappaB, being a central molecule that links the initial acinar injury to systemic inflammation and perpetuate the inflammation, we propose that more studies be focussed towards targeted inhibition of NF-kappaB activity. Direct NF-kappaB inhibition strategies have already been attempted in patients with various cancers. So far, peroxisome proliferator activator receptor gamma (PPAR-gamma) ligand, pyrrolidine dithiocarbamate (PDTC), proteasome inhibitor and calpain I inhibitor have been shown to have direct inhibitory effects on NF-kappaB activation in experimental AP. PMID- 27282981 TI - Comparative proteome analysis reveals proteins involved in salt adaptation in Photobacterium damselae subsp. piscicida. AB - Proteomic approaches were applied to investigate whether Photobacterium damselae subsp. piscicida (Phdp) can directly sense and respond to growth conditions under different salinities, 0.85% and 3.5% NaCl concentrations, mimicking the osmotic conditions in host and marine water bodies, respectively. Proteins significantly altered were analyzed by two-dimensional gel electrophoresis (2-DE), liquid chromatography-electrospray ionization-quadrupole-time-of-flight tandem mass spectrometry (LC-ESI-Q-TOF MS/MS) and bioinformatics analysis, thus resulting in 16 outer membrane proteins (OMPs), 12 inner membrane proteins (IMPs), and 20 cytoplasmic proteins (CPs). Quantitative real-time PCR was also applied to monitor the mRNA expression level of these target proteins. Cluster of orthologous groups of protein (COG) analysis revealed that when shifting from 3.5% to 0.85% salinity, the majority of the up-regulated proteins were involved in posttranslational modification, protein turnover, and chaperones, while the down-regulated proteins were mainly related to energy production and conversion, compatible solutes (carbohydrates, amino acids and their derivatives) biogenesis and transport. Differentially expressed proteins identified in the current study could be used to elucidate the salt adaptation mechanisms of Phdp during their transition between host cells and the marine habitats. PMID- 27282983 TI - Overexploring and overtreating the axilla. PMID- 27282982 TI - Childhood neglect in eating disorders: A systematic review and meta-analysis. AB - Individuals with eating disorders (EDs) often report a history of early traumatization. Although great attention has been paid to certain types of trauma, such as sexual and emotional abuse, less is known about the occurrence of childhood neglect in individuals with EDs. The aim of the present meta-analysis was to provide an estimate of the prevalence of childhood emotional neglect (EN) and physical neglect (PN) in individuals with EDs. A systematic literature search, a critical appraisal of the collected studies, and a meta-analysis were conducted. An electronic search of EMBASE, PsycINFO, PubMed, and the Cochrane Library from the inception of these databases up to July 2015 was performed. The final meta-analyzed data set included 7 studies focusing on EN in EDs (N = 963) and 6 on PN in EDs (N = 665). Our meta-analytic data showed that among individuals with EDs, the prevalence of childhood EN is 53.3%, whereas 45.4% reported experience of childhood PN. These preliminary findings confirm the high prevalence of childhood EN and PN in ED samples compared to the general population and underline the importance of systematically screening for the presence of neglect as a possible traumatic experience in individuals with EDs, as its presence may have important consequences for the therapeutic approach. PMID- 27282984 TI - Prediction of genetic gain in finite populations with heterogeneous predicted breeding values accuracies. AB - The algebraic expression of the genetic selection differential (expected genetic superiority of breeders after a selection on their Predicted Breeding Values) was derived when a limited number of individuals were selected from a limited sample of candidates on the basis of their predicted genetic value, with heterogeneous reliabilities. A formula is proposed for situations in which these reliabilities can be clustered in a few classes. We show that the expected genetic selection differential increases with the number of classes, the mean reliability being constant. In the panel of cases simulated, this increase reached up to 18% of the values obtained in the homogeneous situation. We used the proposed formulae to estimate selection differentials and compared it numerically with performing simulations. In terms of speed of computation, our algebraic formulae performed better than simulations in populations of limited size. PMID- 27282985 TI - Secular trends in the prevalence of type 2 diabetes in adults in China from 1995 to 2014: A meta-analysis. AB - BACKGROUND: The aim of the present study was to estimate trends in the prevalence of type 2 diabetes mellitus (T2DM) in adults in China. METHODS: A systematic search was conducted for studies of T2DM prevalence in adults in China from 2000 to 2014. Pooled prevalence was calculated by a random-effects model. Subgroup and sensitivity analyses were performed. Chi-squared and Cochran-Mantel-Haenszel tests were used to assess differences among subgroups and pooled prevalence, respectively. RESULTS: Forty-six studies (data from 1995 to 2014; 1 463 079 adults) were included in the meta-analysis. The overall prevalence of T2DM was 7.9 %. The pooled prevalence overall and by location (urban and rural), gender (male and female), and age category (18-39, 40-59, and >=60 years) was 4.5 %, 5.1 % and 3.0 %, 4.0 % and 4.2 %, and 1.4 %, 5.0 %, and 10.3 %, respectively, from 1995 to 1999; 6.6 %, 9.3 % and 5.6 %, 7.4 % and 7.5 %, and 1.8 %, 5.9 %, and 12.4 %, respectively, from 2000 to 2004; 10.3 %, 11.8 % and 6.8 %, 10.0 % and 8.6 %, and 2.8 %, 10.3 %, and 20.0 %, respectively, from 2005 to 2009; and 8.3 %, 12.5 % and 7.6 %, 8.6 % and 8.0 %, and 3.5 %, 8.5 %, and 15.3 %, respectively, from 2010 to 2014. The prevalence increased from 5.8 % to 11.6 % with per-capita gross domestic product and differed by diagnostic criteria. CONCLUSIONS: There was a trend of increasing prevalence of T2DM in adults in China from 1995 to 2009, with a decrease in 2010-14 and a greater increase over time in urban versus rural areas, males versus females, and older versus younger adults. PMID- 27282986 TI - Environmental Factors in the Choice of EGMs: A Discrete Choice Experiment. AB - EGMs are a form of entertainment, and the gambling environment is an important contributor to the overall experience. Logically, to select a play-environment, EGM gamblers must choose the platform through which to access the EGM (e.g., internet, mobile application or land-based venue), a particular provider (e.g., specific website, app vendor or branded casino), and the game itself (e.g., based on graphical theme or bonus features; Thorne et al. in J Gambl Stud, 2016. doi: 10.1007/s10899-016-9601-2 ). A discrete choice experiment was conducted to identify the features of the platform, provider and game that are most strongly preferred by EGM gamblers. Participants were 245 EGM gamblers from clubs in Victoria, Australia and 7516 EGM gamblers from an Australian online panel. Results indicate that the ideal environment for the average gambler consists of: gambling at a club that is close to home; with a group of friends; in a relatively quiet place that has air conditioning, cheap food and a large space to play in; on a classic game with quality animations and small bet sizes; where you feel safe and secure; and where there is a wide variety of other games to play when you are done. Segmenting these results by problem-gambler status highlights important differences in preferences between problem and non-problem gamblers. Problem gamblers are less likely to give weight to the company they share and have a preference for larger venues. Using a powerful paradigm from marketing research, the present study was able to determine the relative value of different features of the EGM gambling environment, and also contributes important insight towards what constitutes a safer environment for recreational play. PMID- 27282987 TI - Countertransference in Dermatology. AB - The doctor-patient relationship in dermatology, as in all the fields of medicine, is not a neutral relationship, removed from affects. These affects take root in the sociocultural, professional, family and personal history of both persons in the relationship. They underpin the psychic reality of the patients, along with a variety of representations, preconceived ideas, and fantasies concerning dermatology, the dermatologists or the psychiatrists. Practitioners call these "countertransference feelings", with reference to the psychoanalytical concept of "countertransference". These feelings come forward in a more or less conscious way and are active during the follow-up of any patient: in fact they can facilitate or hinder such a follow-up. Our purpose in focusing on this issue is to sensitize the dermatologists to recognizing these countertransference feelings in themselves (and the attitudes generated by them), in order to allow the patients and doctors to build a dynamic, creative, trustful and effective relationship. PMID- 27282988 TI - Marijuana: Views on Its Medical Use Recorded at the Slovak Social Network. AB - We describe opinions on medical use of Cannabis sativa L under conditions of Slovakia (n = 717). Personal experience with marijuana was detected in 77.42% (n = 553) in age categories younger than 20 years (n = 96) and in 77.06% (n = 457) of adults. Almost 86% of respondents (n = 618) agreed with legal use of marijuana for medical purposes. Furthermore, respondents' views on legal usage of marijuana for medical purposes could be affected by availability of information (r = .12) and personal experience (r = .23). Negative impact of substance abuse in younger age-groups was recognized as threat (r = .47), but knowledge about harmful effect of marijuana use did not affect personal opinion for decriminalization (r = .38). PMID- 27282989 TI - DELLA-mediated PIF degradation contributes to coordination of light and gibberellin signalling in Arabidopsis. AB - Light and gibberellins (GAs) antagonistically regulate hypocotyl elongation in plants. It has been demonstrated that DELLAs, which are negative regulators of GA signalling, inhibit phytochrome-interacting factors 3 and 4 (PIF3 and PIF4) by sequestering their DNA-recognition domains. However, it is unclear whether there are other mechanisms of regulatory crosstalk between DELLAs and PIFs. Here, we demonstrate that DELLAs negatively regulate the abundance of four PIF proteins through the ubiquitin-proteasome system. Reduction of PIF3 protein abundance by DELLAs correlates closely with reduced hypocotyl elongation. Both sequestration and degradation of PIF3 by DELLAs contribute to a reduction in PIF3 binding to its target genes. Thus, we show that promotion of PIF degradation by DELLAs is required to coordinate light and GA signals, and the dual regulation of transcription factors by DELLAs by both sequestration and degradation may be a general mechanism. PMID- 27282990 TI - The poverty of embodied cognition. AB - In recent years, there has been rapidly growing interest in embodied cognition, a multifaceted theoretical proposition that (1) cognitive processes are influenced by the body, (2) cognition exists in the service of action, (3) cognition is situated in the environment, and (4) cognition may occur without internal representations. Many proponents view embodied cognition as the next great paradigm shift for cognitive science. In this article, we critically examine the core ideas from embodied cognition, taking a "thought exercise" approach. We first note that the basic principles from embodiment theory are either unacceptably vague (e.g., the premise that perception is influenced by the body) or they offer nothing new (e.g., cognition evolved to optimize survival, emotions affect cognition, perception-action couplings are important). We next suggest that, for the vast majority of classic findings in cognitive science, embodied cognition offers no scientifically valuable insight. In most cases, the theory has no logical connections to the phenomena, other than some trivially true ideas. Beyond classic laboratory findings, embodiment theory is also unable to adequately address the basic experiences of cognitive life. PMID- 27282992 TI - Erratum to: Are the motor features of verb meanings represented in the precentral motor cortices? Yes, but within the context of a flexible, multilevel architecture for conceptual knowledge. PMID- 27282991 TI - Arguments about the nature of concepts: Symbols, embodiment, and beyond. AB - How are the meanings of words, events, and objects represented and organized in the brain? This question, perhaps more than any other in the field, probes some of the deepest and most foundational puzzles regarding the structure of the mind and brain. Accordingly, it has spawned a field of inquiry that is diverse and multidisciplinary, has led to the discovery of numerous empirical phenomena, and has spurred the development of a wide range of theoretical positions. This special issue brings together the most recent theoretical developments from the leaders in the field, representing a range of viewpoints on issues of fundamental significance to a theory of meaning representation. Here we introduce the special issue by way of pulling out some key themes that cut across the contributions that form this issue and situating those themes in the broader literature. The core issues around which research on conceptual representation can be organized are representational format, representational content, the organization of concepts in the brain, and the processing dynamics that govern interactions between the conceptual system and sensorimotor representations. We highlight areas in which consensus has formed; for those areas in which opinion is divided, we seek to clarify the relation of theory and evidence and to set in relief the bridging assumptions that undergird current discussions. PMID- 27282993 TI - Putting concepts into context. AB - At first glance, conceptual representations (e.g., our internal notion of the object "lemon") seem static; we have the impression that there is something that the concept lemon "means" (a sour, yellow, football-shaped citrus fruit) and that this meaning does not vary. Research in semantic memory has traditionally taken this "static" perspective. Consequently, only effects demonstrated across a variety of contexts have typically been considered informative regarding the architecture of the semantic system. In this review, we take the opposite approach: We review instances of context-dependent conceptual activation at many different timescales-from long-term experience, to recent experience, to the current task goals, to the unfolding process of conceptual activation itself-and suggest that the pervasive effects of context across all of these timescales indicate that rather than being static, conceptual representations are constantly changing and are inextricably linked to their contexts. PMID- 27282994 TI - A delta(15)N assessment of nitrogen deposition for the endangered epiphytic orchid Laelia speciosa from a city and an oak forest in Mexico. AB - Atmospheric nitrogen deposition poses a major threat to global biodiversity. Tropical epiphytic plants are especially at risk given their reliance on atmospheric sources of nutrients. The leaf, pseudobulb, and root carbon and nitrogen content, C:N ratio, as well as the nitrogen isotopic composition were studied for individuals of Laelia speciosa from a city and from an oak forest in Mexico. The nitrogen content of leaves was similar between the city and the oak forest, reaching 1.3 +/- 0.2 % (dry mass). The delta(15)N of leaves, pseudobulbs, and roots reached 5.6 +/- 0.2 0/00 in the city, values found in sites exposed to industrial and vehicular activities. The delta(15)N for plant from the oak forest amounted to -3.1 +/- 0.3 0/00, which is similar to values measured from sites with low industrial activities. Some orchids such as Laelia speciosa produce a single pseudobulb per year, i.e., a water and nutrient storage organ, so the interannual nitrogen deposition was studied by considering the ten most recent pseudobulbs for plants from either site formed between 2003 and 2012. The C:N ratio of the ten most recent pseudobulbs from the oak forest, as well as that of the pseudobulbs formed before 2010 for plants in the city were indistinguishable from each other, averaging 132.4 +/- 6.5, while it was lower for the two most recent pseudobulbs in the city. The delta(15)N values of pseudobulbs from the oak forest averaged -4.4 +/- 0.1 0/00 for the entire series. The delta(15)N ranged from 0.1 +/- 1.6 0/00 for the oldest pseudobulb to 4.7 +/- 0.2 0/00 for the pseudobulb formed in the city from 2008 onwards. Isotopic analysis and the C:N ratio for L. speciosa revealed that rates of nitrogen deposition were higher in the city than in the forest. The delta(15)N values of series of pseudobulbs showed that it is possible to track nitrogen deposition over multiple years. PMID- 27282995 TI - Prognostic significance of PCR-based molecular staging in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy. AB - The prognostic role of detecting clonal immunoglobulin gene rearrangement (IgR) from bone marrow (BM) aspirates was evaluated by BIOMED-2 PCR in 97 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP immunochemotherapy. Sixteen (16.5%) patients had BM involvement (BMI) defined by BM biopsy (MOR+) and 39 (40.2%) had positive IgR (PCR+). Patients with MOR + BMI showed inferior event-free survival (EFS) compared to those with MOR-/PCR- (p < 0.001) or those with MOR-/PCR + BMI (p = 0.002), while no significant difference in EFS was observed between patients with MOR-/PCR + and those with MOR-/PCR - BMI (p = 0.497). Use of the BIOMED-2 for PCR resulted in significant increase in detection of BMI. However, the increased sensitivity by PCR did not translate into improved prediction of prognosis, emphasizing the essential role of histopathological review of trephine biopsy for the detection of BMI. PMID- 27282996 TI - Novel roles for the lens in preserving overall ocular health. AB - Outside the traditional roles of the lens as an important refractive element and a UV filter, it was David Beebe's group that first demonstrated that the lens acts an oxygen sink that protects the tissues of the anterior segment of the eye from oxygen or oxygen metabolites. In this review, we follow on from this work, and present new evidence from our laboratory to demonstrate that the lens serves as a reservoir for the release of the antioxidant glutathione (GSH) into the aqueous humor to provide a source of GSH and/or its precursor amino acids to nearby tissues that interface with the aqueous humor, or to remove toxic metabolites from the eye via the aqueous outflow pathway. In addition to GSH release, our laboratory and others have shown that ATP is released from the lens under hyposmotic conditions to activate purinergic signalling pathways in an autocrine manner to alter lens function. In this review, we raise the idea that ATP and/or its subsequent degradation product adenosine may exert a paracrine function and influence purinergic signalling systems in other tissues to alter aqueous humor outflow. These new secondary roles indicate that the lens is not just a passive optical element, but a highly dynamic and active tissue that interacts with its neighbouring tissues, through modifying the environments in which these tissues function. We believe that the lens actively contributes to the ocular environment and as a consequence, removal of the lens would alter the functionality of neighbouring tissues. We speculate that a long term effect of lens removal may be to inadvertently increase the exposure of anterior tissues of the eye to oxidative stress due to elevated oxygen levels and a reduction in the availability of GSH and purinergic signalling molecules in the aqueous humor. Since cataract surgery is now being performed on younger patients due to our increasing diabetic population, over time, we predict these changes may increase the susceptibility of these tissues to oxidative stress and the incidence of subsequent ocular pathologies. If our view of the lens is correct, the actual loss of the biological lens may have longer term consequences for overall ocular health than currently appreciated. PMID- 27282997 TI - Sucrose and ABA regulate starch biosynthesis in maize through a novel transcription factor, ZmEREB156. AB - Sucrose is not only the carbon source for starch synthesis, but also a signal molecule. Alone or in coordination with ABA, it can regulate the expression of genes involved in starch synthesis. To investigate the molecular mechanisms underlying this effect, maize endosperms were collected from Zea mays L. B73 inbred line 10 d after pollination and treated with sucrose, ABA, or sucrose plus ABA at 28 degrees C in the dark for 24 h. RNA-sequence analysis of the maize endosperm transcriptome revealed 47 candidate transcription factors among the differentially expressed genes. We therefore speculate that starch synthetic gene expression is regulated by transcription factors induced by the combination of sucrose and ABA. ZmEREB156, a candidate transcription factor, is induced by sucrose plus ABA and is involved in starch biosynthesis. The ZmEREB156-GFP-fused protein was localized in the nuclei of onion epidermal cells, and ZmEREB156 protein possessed strong transcriptional activation activity. Promoter activity of the starch-related genes Zmsh2 and ZmSSIIIa increased after overexpression of ZmEREB156 in maize endosperm. ZmEREB156 could bind to the ZmSSIIIa promoter but not the Zmsh2 promoter in a yeast one-hybrid system. Thus, ZmEREB156 positively modulates starch biosynthetic gene ZmSSIIIa via the synergistic effect of sucrose and ABA. PMID- 27282999 TI - A philosophical argument against evidence-based policy. AB - RATIONALE, AIMS AND OBJECTIVES: Evidence-based medicine has two components. The methodological or ontological component consists of randomized controlled trials and their systematic review. This makes use of a difference-making conception of cause. But there is also a policy component that makes a recommendation for uniform intervention, based on the evidence from randomized controlled trials. METHODS: The policy side of evidence-based medicine is basically a form of rule utilitarianism. But it is then subject to an objection from Smart that rule utilitarianism inevitably collapses. If one assumes (1) you should recommend the intervention that has brought most benefit (the core of evidence-based policy making), (2) individual variation (acknowledged by use of randomization) and (3) no intervention benefits all (contingent but true), then the objection can be brought to bear. CONCLUSIONS: A utility maximizer should always ignore the rule in an individual case where greater benefit can be secured through doing so. In the medical case, this would mean that a clinician who knows that a patient would not benefit from the recommended intervention has good reason to ignore the recommendation. This is indeed the feeling of many clinicians who would like to offer other interventions but for an aversion to breaking clinical guidelines. PMID- 27282998 TI - FCGR3A/2A polymorphisms and diffuse large B-cell lymphoma outcome treated with immunochemotherapy: a meta-analysis on 1134 patients from two prospective cohorts. AB - Single nucleotide polymorphisms (SNPs) in FCgamma-receptor genes FCGR3A (rs396991) and FCGR2A (rs1801274) influence the affinity of the Fc portion of anti-CD20 immunoglobulin G1 monoclonal antibody. Their roles in diffuse large B cell lymphoma (DLBCL) treated with rituximab in combination with anthracycline based chemotherapy remain controversial. To address this question, we genotyped FCGR2A and FCGR3A SNPs in two prospective DLBCL cohorts from Lymphoma Study Association trials (N = 554) and Iowa/Mayo Specialized Program Of Research Excellence (N = 580). Correlations with treatment response and hematological toxicity were assessed in Lymphoma Study Association. Correlation with event-free survival (EFS) and overall survival (OS) was performed in both cohorts, followed by a meta-analysis to increase power. Our study shows the absence of correlation between these SNPs and treatment response. Grades 3 and 4 febrile neutropenia during treatment was more frequently observed in FCGR3A VV (39%) than VF (29%) and FF (32%) carriers (p = 0.04). Our analysis for EFS and OS shows that FCGR3A was not associated with outcome. In a meta-analysis using an ordinal model, FCGR2A (per R allele) was associated with a better EFS (hazard ratio = 0.87; 95%CI, 0.76-0.99; p = 0.04) and OS (hazard ratio = 0.86; 95%CI, 0.73-1.00; p = 0.05) which was not altered after adjustment for the International Prognostic Index. Overall, our data demonstrate that patients with DLBCL with the low affinity FCgammaRIIA RR had an unexpectedly better outcome than FCgammaRIIA H carriers. Whether rituximab efficacy is improved in FCgammaRIIA RR patients due a clearance reduction or other functions of FCgammaRIIA in DLBCL should be investigated (clinicaltrials.gov identifiers: NCT00135499, NTC00135499 NCT00140595, NCT00144807, NCT00144755, NCT01087424, and NCT00301821). Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 27283001 TI - The Limping Child - What a Pediatrician Should Know? AB - Diagnosis of a limping child can be challenging for the clinician given the vast array of conditions that present in this manner. This review article discusses the history, examination and subsequent differential diagnoses that should be considered along with the most appropriate investigations for each diagnosis. The latest evidence regarding choice of investigation to make the clinician's task less onerous is also discussed. PMID- 27283003 TI - Poor sleep quality is responsible for the nondipper pattern in hypertensive but not in normotensive chronic kidney disease patients. AB - AIM: This study was designed to evaluate the relationship between sleep quality and hypertension and to determine if there was an association between nondipper blood pressure (BP) and sleep quality in chronic kidney disease (CKD) patients. METHODS: A total of 775 pre-dialysis CKD patients (314 normal BP patients, 461 hypertension patients) defined as dippers or nondippers by ambulatory BP monitoring were recruited for this study. Demographics and clinical correlates were collected, including body mass index, estimated glomerular filtration rate (eGFR) and other measures. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: A total of 185 (58.9%) patients with normal BP and 341 (74.0%) hypertensive patients had a nondipper BP pattern. The hypertension group had a higher prevalence of the nondipper BP pattern, smoking, alcohol intake and diabetes mellitus (DM) and lower eGFR levels and poorer sleep quality than the normal BP group. Patients with the nondipper BP pattern had lower haemoglobin, worse renal function and poorer sleep quality when compared with hypertensive CKD patients with the dipping BP pattern. PSQI scores were significantly associated with the rate of nocturnal BP decline (P < 0.05) in the hypertension group but not in the normal BP group. Poor sleep quality was an independent factor affecting BP pattern in hypertensive CKD patients using multivariate linear and logistic regression analyses. There was no association between sleep quality and hypertension in CKD patients after multivariate logistic regression analyses. CONCLUSION: Poor sleep quality, which is commonly observed in pre-dialysis CKD patients, is an independent associated factor of the nondipper BP pattern in hypertensive CKD patients. No association was found between poor sleep and nondipper BP in normotensive patients. PMID- 27283002 TI - Neural correlates of conversion disorder: overview and meta-analysis of neuroimaging studies on motor conversion disorder. AB - BACKGROUND: Conversion Disorders (CD) are prevalent functional disorders. Although the pathogenesis is still not completely understood, an interaction of genetic, neurobiological, and psychosocial factors is quite likely. The aim of this study is to provide a systematic overview on imaging studies on CDs and investigate neuronal areas involved in Motor Conversion Disorders (MCD). METHODS: A systematic literature search was conducted on CD. Subsequently a meta-analysis of functional neuroimaging studies on MCD was implemented using an Activation Likelihood Estimation (ALE). We calculated differences between patients and healthy controls as well as between affected versus unaffected sides in addition to an overall analysis in order to identify neuronal areas related to MCD. RESULTS: Patients with MCD differ from healthy controls in the amygdala, superior temporal lobe, retrosplenial area, primary motor cortex, insula, red nucleus, thalamus, anterior as well as dorsolateral prefrontal and frontal cortex. When comparing affected versus unaffected sides, temporal cortex, dorsal anterior cingulate cortex, supramarginal gyrus, dorsal temporal lobe, anterior insula, primary somatosensory cortex, superior frontal gyrus and anterior prefrontal as well as frontal cortex show significant differences. CONCLUSIONS: Neuronal areas seem to be involved in the pathogenesis, maintenance or as a result of MCD. Areas that are important for motor-planning, motor-selection or autonomic response seem to be especially relevant. Our results support the emotional unawareness theory but also underline the need of more support by conduction imaging studies on both CD and MCD. PMID- 27283004 TI - Quality and accuracy of publicly accessible cancer-related physical activity information on the Internet: a cross-sectional assessment. AB - In this study, we assessed the quality of publicly available cancer-related physical activity (PA) information appearing on reputable sites from Canada and other English-speaking countries. A cross-sectional Internet search was conducted on select countries (Canada, USA, Australia, New Zealand, UK) using Google to generate top 50 results per country for the keywords "'physical activity' AND 'cancer'". Top results were assessed for quality of PA information based on a coding frame. Additional searches were performed for Canadian-based sites to produce an exhaustive list. Results found that many sites offered cancer-related PA information (94.5%), but rarely defined PA (25.2%). Top 50 results from each country did not differ on any indicator examined. The exhaustive list of Canadian sites found that many sites gave information about PA for survivorship (78.3%) and prevention (70.0%), but rarely defined (6.7%) or referenced PA guidelines (28.3%). Cancer-related PA information is plentiful on the Internet but the quality needs improvement. Sites should do more than mention PA; they should provide definitions, examples and guidelines. With improvements, these websites would enable healthcare providers to effectively educate their patients about PA, and serve as a valuable resource to the general public who may be seeking cancer related PA information. PMID- 27283005 TI - Factors influencing alopecia and hair cortisol in rhesus macaques (Macaca mulatta). AB - BACKGROUND: Alopecia can occur in captive non-human primates, but its etiology is poorly understood. The purpose of this study was to assess alopecia and hair cortisol in rhesus monkeys and to identify the potential risk factors. METHODS: Subjects were 117 rhesus monkeys at two National Primate Research Centers. Photographs and hair samples were obtained during routine physicals. Photographs were analyzed using Image J software to calculate hair loss, and hair samples were assayed for cortisol. RESULTS: Age, days singly housed, and their interactions contributed to the alopecia model for both facilities. Sex and location changes contributed to the hair cortisol model for Facility 1; sedations contributed for Facility 2. Alopecia and hair cortisol were associated at Facility 1. CONCLUSIONS: Captive management practices can affect alopecia and hair cortisol. However, there are facility differences in the relationship between alopecia and hair cortisol and in the effect of intrinsic variables and management procedures. PMID- 27283006 TI - The Health and Libraries of Public Use Retrospective Study (HeLPURS). AB - BACKGROUND: Public libraries may promote health through literacy, education and social connections. OBJECTIVE: To conduct the first broad-based, quantitative exploration of health and public library patronage. METHODS: Retrospective cross sectional study. All 2925 adult patients at a general practice clinic living in a small north-eastern U.S. city were invited by mail to participate; 243 consented. Clinical variables from the medical records were combined with library usage variables from the public library patron database. The authors analysed how patient health characteristics were associated with library cardholding, average card use or recency of use. RESULTS: Approximately 72% of participants held a library card; 40% of these had used it within the last month. Library cardholding was not associated with patient characteristics. Higher average card use was associated with pregnancy, having youth at home and depression severity. Lack of recent library usage was associated with current smoking (P = 0.01) and drug use (P = 0.01). Among ever-smokers, moderate/high card use and card use within six months were both associated with over two times the odds of quitting smoking. CONCLUSIONS: Public libraries and health appear to intersect around substance abuse and depression-anxiety disorders. Moderate or higher use of public libraries is strongly associated with tobacco cessation. PMID- 27283007 TI - Relationship of Myocardial Strain and Markers of Myocardial Injury to Predict Segmental Recovery After Acute ST-Segment-Elevation Myocardial Infarction. AB - BACKGROUND: Late gadolinium-enhanced cardiovascular magnetic resonance imaging overestimates infarct size and underestimates recovery of dysfunctional segments acutely post ST-segment-elevation myocardial infarction. We assessed whether cardiovascular magnetic resonance imaging-derived segmental myocardial strain and markers of myocardial injury could improve the accuracy of late gadolinium enhancement in predicting functional recovery after ST-segment-elevation myocardial infarction. METHODS AND RESULTS: A total of 164 ST-segment-elevation myocardial infarction patients underwent acute (median 3 days) and follow-up (median 9.4 months) cardiovascular magnetic resonance imaging. Wall-motion scoring, feature tracking-derived circumferential strain (Ecc), segmental area of late gadolinium-enhancement (SEE), microvascular obstruction, intramyocardial hemorrhage, and salvage index (MSI) were assessed in 2624 segments. We used logistic regression analysis to identify markers that predict segmental recovery. At acute CMR 32% of segments were dysfunctional, and at follow-up CMR 19% were dysfunctional. Segmental function at acute imaging and odds ratio (OR) for functional recovery decreased with increasing SEE, although 33% of dysfunctional segments with SEE 76% to 100% improved. SEE was a strong predictor of functional improvement and normalization (area under the curve [AUC], 0.840 [95% confidence interval {CI}, 0.814-0.867]; OR, 0.97 [95% CI, 0.97-0.98] per +1% SEE for improvement and AUC, 0.887 [95% CI, 0.865-0.909]; OR, 0.95 [95% CI, 0.94-0.96] per +1% SEE for normalization). Its predictive accuracy for improvement, as assessed by areas under the receiver operator curves, was similar to that of MSI (AUC, 0.840 [95% CI, 0.809-0.872]; OR, 1.03 [95% CI, 1.02-1.03] per +1% MSI for improvement and AUC, 0.862 [0.832-0.891]; OR, 1.04 [95% CI, 1.03-1.04] per +1% SEE for normalization) and Ecc (AUC, 0.834 [95% CI, 0.807-0.862]; OR, 1.05 [95% CI, 1.03-1.07] per +1% MSI for improvement and AUC, 0.844 [95% CI, 0.818-0.871]; OR, 1.07 [95% CI, 1.05-1.10] per +1% SEE for normalization), and for normalization was greater than the other predictors. MSI and Ecc remained as significant after adjustment for SEE but provided no significant increase in predictive accuracy for improvement and normalization compared with SEE alone. MSI had similar predictive accuracy to SEE for functional recovery but was not assessable in 25% of patients. Microvascular obstruction provided no incremental predictive accuracy above SEE. CONCLUSIONS: This multicenter study confirms that SEE is a strong predictor of functional improvement post ST-segment-elevation myocardial infarction, but recovery occurs in a substantial proportion of dysfunctional segments with SEE >75%. Feature tracking-derived Ecc and MSI provide minimal incremental benefit to SEE in predicting segmental recovery. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique identifier: ISRCTN70913605. PMID- 27283008 TI - Myocardial Deformation Imaging by Feature-Tracking Cardiac Magnetic Resonance in Acute Myocardial Infarction: Do We Need It? PMID- 27283009 TI - Correlation of Venous Blood Gas and Pulse Oximetry With Arterial Blood Gas in the Undifferentiated Critically Ill Patient. AB - RATIONALE: Blood gas analysis is often used to assess acid-base, ventilation, and oxygenation status in critically ill patients. Although arterial blood gas (ABG) analysis remains the gold standard, venous blood gas (VBG) analysis has been shown to correlate with ABG analysis and has been proposed as a safer less invasive alternative to ABG analysis. OBJECTIVE: The purpose of this study was to evaluate the correlation of VBG analysis plus pulse oximetry (SpO2) with ABG analysis. METHODS: We performed a prospective cohort study of patients in the emergency department (ED) and intensive care unit (ICU) at a single academic tertiary referral center. Patients were eligible for enrollment if the treating physician ordered an ABG. Statistical analysis of VBG, SpO2, and ABG data was done using paired t test, Pearson chi2, and Pearson correlation. MAIN RESULTS: There were 156 patients enrolled, and 129 patients completed the study. Of the patients completing the study, 53 (41.1%) were in the ED, 41 (31.8%) were in the medical ICU, and 35 (27.1%) were in the surgical ICU. The mean difference for pH between VBG and ABG was 0.03 (95% confidence interval: 0.03-0.04) with a Pearson correlation of 0.94. The mean difference for pCO2 between VBG and ABG was 4.8 mm Hg (95% confidence interval: 3.7-6.0 mm Hg) with a Pearson correlation of 0.93. The SpO2 correlated well with PaO2 (the partial pressure of oxygen in arterial blood) as predicted by the standard oxygen-hemoglobin dissociation curve. CONCLUSION: In this population of undifferentiated critically ill patients, pH and pCO2 on VBG analysis correlated with pH and pCO2 on ABG analysis. The SpO2 correlated well with pO2 on ABG analysis. The combination of VBG analysis plus SpO2 provided accurate information on acid-base, ventilation, and oxygenation status for undifferentiated critically ill patients in the ED and ICU. PMID- 27283010 TI - Implant surface roughness alterations induced by different prophylactic procedures: an in vitro study. AB - AIM: To evaluate surface roughness alterations at the smooth neck of dental implants after the use of eight different prophylactic procedures. MATERIALS AND METHODS: 50 tissue level implants (Institut Straumann AG, Basel, Switzerland) were used for the present investigation. The smooth collar of each implant was divided into two segments, each treated with one of eight cleaning procedures: use of a rubber cup (RCZ) or a brush (BZ) combined with an abrasive paste containing zirconium or a paste derived from perlite (RCP, BP); use of 2 composite resin burs reinforced by zirconium glass fibers (F1, F2); and use of an air-polishing system with glycine powder and two power settings (AP1, AP2). The qualitative alterations were recorded by means of a laser profilometer and the mean roughness (Ra ) and mean roughness profile depth (Rz ) were reported. Twenty untreated surfaces were used as controls. RESULTS: The implant collars treated with RCZ (Ra = 0.33 MUm, Rz = 2.43 MUm) or BZ (Ra = 0.30 MUm, Rz = 3.70 MUm) yielded the highest roughness values, followed by the surfaces treated with RCP (Ra = 0.28 MUm, Rz = 2.02 MUm), with BP (Ra = 0.25 MUm, Rz = 2.16 MUm) and by the use of F1 (Ra = 0.27 MUm, Rz = 2.22 MUm) and F2 (Ra = 0.27 MUm, Rz = 2.04 MUm). The lowest roughness values were observed in the AP1 (Ra = 0.23 MUm, Rz = 1.60 MUm) and AP2 (Ra = 0.16 MUm, Rz = 1.06 MUm) group, respectively. Implant collars treated with AP2 yielded statistically significantly lower (P = 0.01) Rz values compared with untreated surfaces. CONCLUSION: All tested procedures did not increase implant surface roughness significantly. Treatment with an air powder abrasive system at high-pressure setting resulted in a smoothening of the implant collar surface. PMID- 27283011 TI - Projecting the impact of hypothetical early life interventions on adiposity in children living in low-income households. AB - BACKGROUND: It is difficult to evaluate the effectiveness of interventions aimed at reducing early childhood obesity using randomized trials. Objective To illustrate how observational data can be analysed using causal inference methods to estimate the potential impact of behavioural 'interventions' on early childhood adiposity. Methods We used longitudinal data from 1054 children 1-5 years old enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children and followed (WIC) from 2008 to 2010 for a mean duration of 23 months. The data came from a random sample of WIC families living in Los Angeles County in 2008. We used the parametric g-formula to estimate the impact of various hypothetical behavioural interventions. Results Adjusted mean weight for-height Z score at the end of follow-up was 0.73 (95% CI 0.65, 0.81) under no intervention and 0.63 (95% CI 0.38, 0.87) for all interventions given jointly. Exclusive breastfeeding for 6 months or longer was the most effective intervention [population mean difference = -0.11 (95% CI -0.22, 0.01)]. Other interventions had little or no effect. Conclusions Compared with interventions promoting healthy eating and physical activity behaviours, breastfeeding was more effective in reducing obesity risk in children aged 1-5 years. When carefully applied, causal inference methods may offer viable alternatives to randomized trials in etiologic and evaluation research. PMID- 27283012 TI - Challenges in pancreas transplantation. AB - Whole-organ pancreas transplantation, either alone or combined with a kidney transplant, is the only definitive treatment for many patients with type 1 diabetes that restores normal glucose homoeostasis and insulin independence. Pancreas transplantation delays, or potentially prevents, secondary diabetes complications and is associated with improvement in patient survival when compared with either patients remaining on the waiting list or those receiving kidney transplant alone. Pancreas transplantation is safe and effective, with 1 year patient survival >97 % and graft survival rates of 85 % at 1 year and 76 % at 5 years in recent UK data. This review focuses on some current areas of interest in pancreas transplantation. PMID- 27283013 TI - Transient Postnatal Gonadal Activation and Growth Velocity in Infancy. AB - BACKGROUND AND OBJECTIVE: Transient activation of the hypothalamic-pituitary gonadal axis with a sex steroid surge is observed in boys and girls during the first months of life. However, the role of sex steroids in the regulation of growth has not been substantiated in infancy. We tested the hypothesis that testosterone (T) surge, known to be higher in infant boys than in girls during the transient postnatal gonadal activation regulates linear growth in infants. METHODS: To characterize in detail the linear growth velocity (GV) differences between genders in the normal population in early infancy, we evaluated growth of 18 570 healthy infants (51.0% boys) with 162 003 height measurements from birth to 12 months of age. GV was monitored and compared with serially measured urinary T and estradiol levels and serum insulin-like growth factor 1 levels in 84 healthy infants (45% boys) during the first 6 months of life. RESULTS: GV was significantly faster from birth to 6 months of age in boys than in girls (P <= .01). The greatest GV difference, 4.1 cm per year, was observed at 1 month of age, simultaneously with the peak of postnatal gonadal activation. In the mixed model analysis, GV showed a significant positive association with T in both genders (parameter estimate up to 0.62, 95% confidence interval 0.44-0.81). CONCLUSIONS: These results provide a new insight into the regulation of growth in infants and elucidate a novel biological role of the transient postnatal gonadal activation in growth regulation. PMID- 27283014 TI - Mini-Puberty and Growth. PMID- 27283015 TI - Ultrasound Assisted Endovascular Thrombolysis in Adolescents: 2 Case Reports. AB - Descending iliofemoral thrombosis in children is a rare event. Anticoagulation therapy with low-molecular-weight-heparin is standard of care. However, patency cannot be achieved in all cases, increasing the risk for rethrombosis and postthrombotic syndrome. To reduce the risk of venous valve failure in adults, local catheter-directed thrombolysis is used to reopen vessels. Two adolescent girls (17 and 15 years old) presented with acute descending iliofemoral thrombosis of the left common iliac, external, and common femoral veins. Anticoagulation with enoxaparin was started until insertion of an EkoSonic Mach 4e catheter for ultrasound-assisted local thrombolysis with recombinant tissue plasminogen activator and administration of unfractionated heparin. Success was monitored by increases in D-dimer levels and ultrasound findings. After 24 hours respectively 48 hours, complete recanalization was obtained. No complication occurred except minimal local bleeding. Screening for hereditary thrombophilia revealed a heterozygous antithrombin mutation in 1 girl (ie, the 15-year-old). May-Thurner syndrome was identified in both girls, necessitating stenting of the left common iliac veins and continuation of anticoagulation therapy with enoxaparin and acetylsalicylic acid. No rethrombosis or complications occurred during the follow-up period. Ultrasound-assisted catheter-directed local thrombolysis with the EkoSonic Mach 4e system was effective in achieving immediate recanalization of the occluded veins and should be considered in children experiencing descending iliofemoral thrombosis. The fast recanalization might reduce the incidence of postthrombotic syndrome. May-Thurner syndrome is regularly found in these patients, and if present, requires stenting of the common iliac vein to avoid early reocclusion. However, long-term patency of iliac vein stenting in children remains to be examined. PMID- 27283016 TI - Naturally occurring recombination in ferret coronaviruses revealed by complete genome characterization. AB - Ferret coronaviruses (FRCoVs) exist as an enteric and a systemic pathotype, of which the latter is highly lethal to ferrets. To our knowledge, this study provides the first full genome sequence of a FRCoV, tentatively called FRCoV-NL 2010, which was detected in 2010 in ferrets in The Netherlands. Phylogenetic analysis showed that FRCoV-NL-2010 is most closely related to mink CoV, forming a separate clade of mustelid alphacoronavirus that split off early from other alphacoronaviruses. Based on sequence homology of the complete genome, we propose that these mustelid coronaviruses may be assigned to a new species. Comparison of FRCoV-NL-2010 with the partially sequenced ferret systemic coronavirus MSU-1 and ferret enteric coronavirus MSU-2 revealed that recombination in the spike, 3c and envelope genes occurred between different FRCoVs. PMID- 27283017 TI - Design, Synthesis, and Biological Evaluation of 4-Phenoxyquinoline Derivatives Containing Benzo[d]thiazole-2-yl Urea as c-Met Kinase Inhibitors. AB - A series of novel 4-phenoxyquinoline derivatives containing the benzo[d]thiazole 2-yl urea moiety were synthesized and evaluated for their cytotoxicity against the HT-29, MKN-45, and H460 cell lines. The structures of the target compounds were confirmed by (1) H NMR and MS spectra. Most of them showed moderate to excellent potency against the three tested cell lines. Especially, compound 23 was identified a promising agent (c-Met IC50 = 17.6 nM), showing the most potent anticancer activities with IC50 values of 0.18, 0.06, and 0.01 uM against the HT 29, MKN-45, and H460 cell lines, respectively. The docking results of 23 with the c-Met kinase model 3LQ8 showed a specific binding mode between the ligand and the target protein. PMID- 27283018 TI - Thinking Outside of Outpatient: Underutilized Settings for Psychotherapy Education. AB - OBJECTIVE: Although psychiatry residents are expected to achieve competency in conducting psychotherapy during their training, it is unclear how psychotherapy teaching is integrated across diverse clinical settings. METHODS: Between January and March 2015, 177 psychiatry residency training directors were sent a survey asking about psychotherapy training practices in their programs, as well as perceived barriers to psychotherapy teaching. RESULTS: Eighty-two training directors (44%) completed the survey. While 95% indicated that psychotherapy was a formal learning objective for outpatient clinic rotations, fifty percent or fewer noted psychotherapy was a learning objective in other settings. Most program directors would like to see psychotherapy training included (particularly supportive psychotherapy and cognitive behavioral therapy) on inpatient (82%) and consultation-liaison settings (57%). The most common barriers identified to teaching psychotherapy in these settings were time and perceived inadequate staff training and interest. CONCLUSIONS: Non-outpatient rotations appear to be an underutilized setting for psychotherapy teaching. PMID- 27283019 TI - Profile of microbial communities on carbonate stones of the medieval church of San Leonardo di Siponto (Italy) by Illumina-based deep sequencing. AB - Comprehensive studies of the biodiversity of the microbial epilithic community on monuments may provide critical insights for clarifying factors involved in the colonization processes. We carried out a high-throughput investigation of the communities colonizing the medieval church of San Leonardo di Siponto (Italy) by Illumina-based deep sequencing. The metagenomic analysis of sequences revealed the presence of Archaea, Bacteria, and Eukarya. Bacteria were Actinobacteria, Proteobacteria, Bacteroidetes, Cyanobacteria, Chloroflexi, Firmicutes and Candidatus Saccharibacteria. The predominant phylum was Actinobacteria, with the orders Actynomycetales and Rubrobacteriales, represented by the genera Pseudokineococcus, Sporichthya, Blastococcus, Arthrobacter, Geodermatophilus, Friedmanniella, Modestobacter, and Rubrobacter, respectively. Cyanobacteria sequences showing strong similarity with an uncultured bacterium sequence were identified. The presence of the green algae Oocystaceae and Trebuxiaceae was revealed. The microbial diversity was explored at qualitative and quantitative levels, evaluating the richness (the number of operational taxonomic units (OTUs)) and the abundance of reads associated with each OTU. The rarefaction curves approached saturation, suggesting that the majority of OTUs were recovered. The results highlighted a structured community, showing low diversity, made up of extremophile organisms adapted to desiccation and UV radiation. Notably, the microbiome appeared to be composed not only of microorganisms possibly involved in biodeterioration but also of carbonatogenic bacteria, such as those belonging to the genus Arthrobacter, which could be useful in bioconservation. Our investigation demonstrated that molecular tools, and in particular the easy-to-run next-generation sequencing, are powerful to perform a microbiological diagnosis in order to plan restoration and protection strategies. PMID- 27283021 TI - A phylogenetic study of the tribe Antirrhineae: Genome duplications and long distance dispersals from the Old World to the New World. AB - PREMISE OF THE STUDY: Antirrhineae is a large tribe within Plantaginaceae. Mostly concentrated in the Mediterranean Basin, the tribe members are present both in the Old World and the New World. Current Antirrhineae phylogenies have different views on taxonomic relationships, and they lack homogeneity in terms of geographic distribution and ploidy levels. This study aims to investigate the changes in the chromosome numbers along with dispersal routes as definitive characters identifying clades. METHODS: With the use of multiple DNA regions and taxon sampling enriched with de novo sequences, we provide an extensive phylogeny for Antirrhineae. The reconstructed phylogeny was then used to investigate changes in ploidy levels and dispersal patterns in the tribe using ChromEvol and RASP, respectively. KEY RESULTS: Antirrhineae is a monophyletic group with six highly supported clades. ChromEvol analysis suggests the ancestral haploid chromosome number for the tribe is six, and that the tribe has experienced several duplications and gain events. The Mediterranean Basin was estimated to be the origin for the tribe with four long-distance dispersals from the Old World to the New World, three of which were associated with genome duplications. CONCLUSIONS: On an updated Antirrhineae phylogeny, we showed that the three out of four dispersals from the Old World to the New World were coupled with changes in ploidy levels. The observed patterns suggest that increases in ploidy levels may facilitate dispersing into new environments. PMID- 27283022 TI - Common mycelial networks impact competition in an invasive grass. AB - PREMISE OF THE STUDY: Mycorrhizal hyphal complexes can connect multiple host plants to form common mycelial networks (CMNs) that may affect plant competitive outcomes and community composition through differential resource allocation. The impacts of CMN interactions on invasive plants are not well understood and could be crucial to the understanding of invasive plant establishment and success. METHODS: We grew the invasive grass Brachypodium sylvaticum in intra- and interspecific pairings with native grass Bromus vulgaris in a greenhouse and controlled for the effects of CMN and root interactions by manipulating the belowground separation between competitors. Comparison of plant growth in pots that allowed CMN interactions and excluded root competition and vice versa, or both, allowed us to delineate the effects of network formation and root competition on invasive plant establishment and performance. KEY RESULTS: Brachypodium sylvaticum grown in pots allowing for only hyphal interactions, but no root competition, displayed superior growth compared with conspecifics in other treatments. Invasive performance was poorest when pairs were not separated by a barrier. Shoot nitrogen content in B. sylvaticum was higher in mycorrhizal plants only when connections were allowed between competitors. CONCLUSIONS: Our results indicate that the presence of CMN networks can have positive effects on B. sylvaticum establishment and nutrient status, which may affect plant competition and invasion success. PMID- 27283020 TI - Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling. AB - BACKGROUND: The lysophospholipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are pleiotropic signaling molecules with a broad range of physiological functions. Targeting the S1P1 receptor on lymphocytes with the immunomodulatory drug fingolimod has proven effective in the treatment of multiple sclerosis. An emerging body of experimental evidence points to additional direct effects on cells of the central and peripheral nervous system. Furthermore, fingolimod has been reported to reduce LPA synthesis via inhibition of the lysophospholipase autotaxin. Here we investigated whether modulation of particular signaling aspects of S1P as well as LPA by fingolimod might propagate peripheral nerve regeneration in vivo and independent of its anti-inflammatory potency. METHODS: Sciatic nerve crush was performed in wildtype C57BL/6, in immunodeficient Rag1 (-/-) and Foxn1 (-/-) mice. Analyses were based on walking track analysis and electrophysiology, histology, and cAMP formation. Quantification of different LPA species was performed by liquid chromatography coupled to tandem mass spectrometry. Furthermore, functional consequences of autotaxin inhibition by the specific inhibitor PF-8380 and the impact of fingolimod on early cytokine release in the injured sciatic nerve were investigated. RESULTS: Clinical and electrophysiological measures indicated an improvement of nerve regeneration under fingolimod treatment that is partly independent of its anti-inflammatory properties. Fingolimod treatment correlated with a significant elevation of axonal cAMP, a crucial factor for axonal outgrowth. Additionally, fingolimod significantly reduced LPA levels in the injured nerve. PF-8380 treatment correlated with improved myelin thickness. Sciatic nerve cytokine levels were not found to be significantly altered by fingolimod treatment. CONCLUSIONS: Our findings provide in vivo evidence for direct effects of fingolimod on cells of the peripheral nervous system that may propagate nerve regeneration via a dual mode of action, differentially affecting axonal outgrowth and myelination by modulating relevant aspects of S1P and LPA signaling. PMID- 27283023 TI - Absence of postmating barriers between a selfing vs. outcrossing Chilean Mimulus species pair. AB - PREMISE OF THE STUDY: Reproductive isolation between sympatric species pairs may be maintained by both pre- and postmating barriers. Here we evaluate potential barriers to mating between the outcrossing Mimulus luteus and its more highly selfing sympatric congener, M. cupreus, two members of the South American luteus complex of Mimulus. METHODS: Seed set was compared following autonomous self pollination, manual pollination, conspecific outcrossing, and sympatric and allopatric hybridization, for laboratory-maintained inbred lines and wild collected accessions. Survival and reproductive fitness of hybrids relative to parental species were examined across environments that differed with respect to temperature and soil nutrients, two factors that vary across the ranges of M. luteus and M. cupreus. KEY RESULTS: Mimulus luteus was minimally capable of autonomous self-fertilization, consistent with reliance on an animal pollinator, whereas M. cupreus was a successful selfer across all tested accessions. Postmating barriers to hybridization are negligible, in both low- and high-stress environments, across multiple sympatric and allopatric populations. CONCLUSION: As in the North American M. guttatus-M. nasutus species pair, postmating barriers contribute little to isolation between M. luteus and M. cupreus. This result reinforces the importance of premating barriers, specifically species differences in reliance on, and accessibility to, animal pollinators. A unique aspect of the M. luteus-M. cupreus pair is the recent gain of red floral anthocyanin pigmentation in M. cupreus. On the basis of species differences in vegetative anthocyanin production, a facultative stress-protective response, we propose a potential stress-protective role for the constitutive floral anthocyanins of M. cupreus. PMID- 27283024 TI - Computational haemodynamic analysis of left pulmonary artery angulation effects on pulmonary blood flow. AB - OBJECTIVES: To study the effect of the angulation between the left pulmonary artery (LPA) and the main pulmonary artery on pulmonary haemodynamics. METHODS: A 3D model of patient-specific pulmonary artery (PA) was reconstructed as an original model. Four models with descendent LPA angulation equalled to 120 degrees , 110 degrees , 100 degrees and 90 degrees , were reconstructed by computer-aided design for the virtual simulation of the pulmonary flow under different surgical strategies. Computational fluid dynamics was introduced to calculate the pulmonary blood flow in five models. Streamlines, wall shear stress, energy loss and flow distribution ratio were calculated and compared to determine the better haemodynamics in the pulmonary artery. RESULTS: Vortices were formed at the lower wall of the opening of right PA and LPA in models with LPA angles equal to or less than 100 degrees (Models 3 and 4). Relative high wall shear stress areas at the lateral and lower wall of LPA opening had an ascendant tendency as the angle declined. Decreased flow distribution ratio to left lung (original model: 0.58, Model 1: 0.63, Model 2: 0.586, Model 3: 0.564, Model 4: 0.55) and increased energy loss (original model: 385.2 mV, Model 1: 239.4 mV, Model 2: 384.3 mV, Model 3: 430.9 mV, Model 4: 439.8 mV) in a cardiac cycle were noted as the angle reduced. CONCLUSIONS: Acute LPA angulation is associated with adverse haemodynamic performance. This should be particularly addressed during the reconstruction of pulmonary artery in the repair of tetralogy of Fallot. PMID- 27283025 TI - The experimental validation of free fat grafts in thoracic surgery. AB - We evaluated the viability of free fat grafts in the thoracic cavity using 3 month old male swine (n = 2). After left caudal lobectomy, 1-3 g of subcutaneous fat tissue harvested via the thoracotomy site was implanted in the chest cavity. At re-thoracotomy 6 weeks after implantation, all of the implanted fat grafts (n = 15) were found to have closely adhered to the parietal pleura and visceral pleura. There was a significant decrease by ~30% in the weight of the fat grafts after implantation. Regardless of the weight loss, the implanted fat graft showed normal structuring without scar formation in the central area. Our results may suggest that free fat pads, which weighed up to 3 g, were successfully cultured in the thoracic cavity until the implanted tissues integrated into the surrounding tissues. Therefore, the free fat pad can be used as a biomaterial for some purposes in thoracic surgery. PMID- 27283027 TI - Passivated ambipolar black phosphorus transistors. AB - We report the first air-passivated ambipolar BP transistor formed by applying benzyl viologen, which serves as a surface charge transfer donor for BP flakes. The passivated BP devices exhibit excellent stability under both an ambient atmosphere and vacuum; their transistor performance is maintained semi permanently. Unlike their intrinsic p-type properties, passivated BP devices present advantageous ambipolar properties with much higher electron mobility up to ~83 cm(2) V(-1) s(-1) from 2-terminal measurement at 300 K, compared to other reported studies on n-type BP transistors. On the basis of the n-type doping effect that originated from benzyl viologen, we also systematically investigated the BP thickness dependence of our devices on electrical properties, in which we found the best electron transport performance to be attained when an ~10 nm thick BP flake was used. PMID- 27283026 TI - Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells. AB - Tissue plasminogen activator (tPA), aside from its vascular fibrinolytic action, exerts various effects within the body, ranging from synaptic plasticity to control of cell fate. Here, we observed that by activating plasminogen and matrix metalloproteinase-9, tPA expands murine bone marrow-derived CD45(-)TER119(-)Sca 1(+)PDGFRalpha(+) mesenchymal stromal cells (PalphaS-MSCs) in vivo through a crosstalk between PalphaS-MSCs and endothelial cells. Mechanistically, tPA induces the release of Kit ligand from PalphaS-MSCs, which activates c-Kit(+) endothelial cells to secrete MSC growth factors: platelet-derived growth factor BB (PDGF-BB) and fibroblast growth factor 2 (FGF2). In synergy, FGF2 and PDGF-BB upregulate PDGFRalpha expression in PalphaS-MSCs, which ultimately leads to PalphaS-MSC expansion. These data show a novel mechanism by which the fibrinolytic system expands PalphaS-MSCs through a cytokine crosstalk between niche cells. PMID- 27283028 TI - Faculty Development for Fostering Clinical Reasoning Skills in Early Medical Students Using a Modified Bayesian Approach. AB - PROBLEM: Clinical reasoning is a necessary skill for medical students to acquire in the course of their education, and there is evidence that they can start this process at the undergraduate level. However, physician educators who are experts in their given fields may have difficulty conveying their complex thought processes to students. Providing faculty development that equips educators with tools to teach clinical reasoning may support skill development in early medical students. INTERVENTION: We provided faculty development on a modified Bayesian method of teaching clinical reasoning to clinician educators who facilitated small-group, case-based workshops with 2nd-year medical students. We interviewed them before and after the module regarding their perceptions on teaching clinical reasoning. We solicited feedback from the students about the effectiveness of the method in developing their clinical reasoning skills. CONTEXT: We carried out this project during an institutional curriculum rebuild where clinical reasoning was a defined goal. At the time of the intervention, there was also increased involvement of the Teaching and Learning Center in elevating the status of teaching and learning. OUTCOME: There was high overall satisfaction with the faculty development program. Both the faculty and the students described the modified Bayesian approach as effective in fostering the development of clinical reasoning skills. LESSONS LEARNED: Through this work, we learned how to form a beneficial partnership between a clinician educator and Teaching and Learning Center to promote faculty development on a clinical reasoning teaching method for early medical students. We uncovered challenges faced by both faculty and early learners in this study. We observed that our faculty chose to utilize the method of teaching clinical reasoning in a variety of manners in the classroom. Despite obstacles and differing approaches utilized, we believe that this model can be emulated at other institutions to foster the development of clinical reasoning skills in preclerkship students. PMID- 27283031 TI - Letter to the Editor: Avoiding a lost opportunity for psychological medicine: importance of chimpanzee research to the National Institutes of Health portfolio. PMID- 27283029 TI - The recovery trajectory of adolescent social defeat stress-induced behavioral, (1)H-MRS metabolites and myelin changes in Balb/c mice. AB - Adolescent exposure to social stress precipitates emotion-related disorders and affects the development and function of medial prefrontal cortex (mPFC). However, this adversity-induced behavioral and neurological changes remain not fully explored. Adolescent Balb/c mice were subjected to intermittent social defeat stress during postnatal days 28 to 42. Proton magnetic resonance spectroscopy ((1)H-MRS) measurements, behavioral tests and immunohistochemistry were performed one day or 3 weeks after the last stress episode. Defeated mice exhibited hypoactivity and social avoidance with the latter lasting into the early adulthood, while the anxiety level was unchanged. Social defeat experience lead to temporary decreases in the levels of total creatines (Cr + pCr) and Glx (Glu + Gln), but a delayed increase of N- acetylaspartate (NAA) levels. These alternations were accompanied with a persistent reduction of myelin basic protein expression although the number of mature oligodendrocyte did not change. These findings provide evidence that adolescent adverse social experience permanently impairs the emotion-related behavioral performance and induces biochemical and molecular changes in the brain which at least lasts into early adulthood, thus enhancing our understanding of the neurobiology of social defeat stress. Our finding also implicates that NAA signals on MRS may reflect myelin status. PMID- 27283032 TI - Novel mechanisms of atherosclerosis and cardiovascular repair. PMID- 27283033 TI - CardioPulse Articles. PMID- 27283030 TI - Human Herpesvirus 8-Unrelated Primary Effusion Lymphoma-Like Lymphoma in an Elderly Korean Patient with a Good Response to Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone. AB - Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin's lymphoma arising from a B-cell lineage characterized by the formation of malignant effusion in body cavities without evidence of a detectable tumor. The effusion contains tumor cells universally infected with human herpesvirus 8 (HHV8), which is the critical factor differentiating PEL from HHV8-unrelated PEL-like lymphoma (PEL-LL). This report describes a 77-year-old male patient with pleural effusion and ascites, containing lymphoma cells expressing a B-cell phenotype, but without markers of HHV8 in immunocytochemical analysis. The patient was diagnosed with PEL-LL and treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), which resulted in a complete remission. The patient is currently disease-free 15 months post-treatment. To the best of our knowledge, this is the first report on administration of R-CHOP in a PEL-LL patient in South Korea. PMID- 27283034 TI - Screening of saponins and sapogenins from Medicago species as potential PPARgamma agonists and X-ray structure of the complex PPARgamma/caulophyllogenin. AB - A series of saponins and sapogenins from Medicago species were tested for their ability to bind and activate the nuclear receptor PPARgamma by SPR experiments and transactivation assay, respectively. The SPR analysis proved to be a very powerful and fast technique for screening a large number of compounds for their affinity to PPARgamma and selecting the better candidates for further studies. Based on the obtained results, the sapogenin caulophyllogenin was proved to be a partial agonist towards PPARgamma and the X-ray structure of its complex with PPARgamma was also solved, in order to investigate the binding mode in the ligand binding domain of the nuclear receptor. This is the first known crystal structure of a sapogenin directly interacting with PPARgamma. Another compound of the series, the echinocistic acid, showed antagonist activity towards PPARgamma, a property that could be useful to inhibit the adipocyte differentiation which is a typical adverse effect of PPARgamma agonists. This study confirms the interest on saponins and sapogenins as a valuable natural resource exploitable in the medical and food industry for ameliorating the metabolic syndrome.